PMID- 15235811
TI  - Sensory processing of ambient CO2 information in the brain of the moth Manduca
      sexta.
AB  - Insects use information about CO2 to perform vital tasks such as locating food
      sources. In certain moths, CO2 is involved in oviposition behavior. The labial
      palps of adult moths that feed as adults have a pit organ containing sensory
      receptor cells that project into the antennal lobes, the sites of primary
      processing of olfactory information in the brain. In the moth Manduca sexta and
      certain other species of Lepidoptera, these receptor cells in the labial-palp pit
      organ have been shown to be tuned to CO2, and their axons project to a single,
      identified glomerulus in the antennal lobe, the labial-palp pit organ glomerulus.
      At present, however, nothing is known about the function of this glomerulus or
      how CO2 information is processed centrally. We used intracellular recording and
      staining to reveal projection (output) neurons in the antennal lobes that respond
      to CO2 and innervate the labial-palp pit organ glomerulus. Our results
      demonstrate that this glomerulus is the site of first-order processing of sensory
      information about ambient CO2. We found three functional types of CO2-responsive
      neurons (with their cell bodies in the antennal lobe or the protocerebrum) that
      provide output from the antennal lobe to higher centers in the brain. Some
      physiological characteristics of those neurons are described.

PMID- 15235812
TI  - Computer-assisted detection of pulmonary nodules: performance evaluation of an
      expert knowledge-based detection system in consensus reading with experienced and
      inexperienced chest radiologists.
AB  - To evaluate the performance of experienced versus inexperienced radiologists in
      comparison and in consensus with an interactive computer-aided detection (CAD)
      system for detection of pulmonary nodules. Eighteen consecutive patients (mean
      age: 62.2 years; range 29-83 years) prospectively underwent routine 16-row
      multislice computed tomography (MSCT). Four blinded radiologists (experienced:
      readers 1, 2; inexperienced: readers 3, 4) assessed image data against CAD for
      pulmonary nodules. Thereafter, consensus readings of readers 1+3, reader 1+CAD
      and reader 3+CAD were performed. Data were compared against an independent gold
      standard. Statistical tests used to calculate interobserver agreement, reader
      performance and nodule size were Kappa, ROC and Mann-Whitney U. CAD and
      experienced readers outperformed inexperienced readers (Az=0.72, 0.71, 0.73, 0.49
      and 0.50 for CAD, readers 1-4, respectively; P<0.05). Performance of reader 1+CAD
      was superior to single reader and reader 1+3 performances (Az=0.93, 0.72 for
      reader 1+CAD and reader 1+3 consensus, respectively, P<0.05). Reader 3+CAD did
      not perform superiorly to experienced readers or CAD (Az=0.79 for reader 3+CAD;
      P>0.05). Consensus of reader 1+CAD significantly outperformed all other readings,
      demonstrating a benefit in using CAD as an inexperienced reader replacement. It
      is questionable whether inexperienced readers can be regarded as adequate for
      interpretation of pulmonary nodules in consensus with CAD, replacing an
      experienced radiologist.

PMID- 15235813
TI  - Transgene expression in strawberries driven by a heterologous phloem-specific
      promoter.
AB  - Strawberry is susceptible to diseases caused by phytoplasmas, mycoplasma-like
      prokaryotes restricted to sieve elements in the phloem tissue of infected plants.
      One strategy to improve strawberry resistance to phytoplasmas involves transgenic
      expression of anti-microbial peptide genes in phloem. For targeted phloem
      specific expression, we constructed a binary vector with an expression cassette
      bearing the beta-glucuronidase (GUS) reporter gene (uidA) under control of the
      Arabidopsis sucrose-H+ symporter gene (AtSUC2) promoter. Transgenic strawberry
      lines were generated with high efficiencies by a modified transformation
      protocol, which combines the adoption of a 3-day pre-selection period following
      transformation, and the addition of 10-microM thidiazuron to the regeneration
      medium. Histological GUS activity indicated that the reporter gene was expressed
      specifically in phloem of leaves, petioles, and roots of transgenic plants. The
      results suggest that the transformation protocol and the AtSUC2 promoter may be
      useful for engineering phytoplasma-resistant transgenic strawberries.

PMID- 15235814
TI  - Effect of medium osmotic potential on callus induction and shoot regeneration in
      flax anther culture.
AB  - Development of an efficient and cost-effective doubled haploid production system
      in flax (Linum usitatissimum L.) is the prerequisite for the application of
      doubled haploid technology in a practical breeding program. Pre-culture of
      anthers on a medium containing 15% sucrose for 2-7 days before transfer to the
      same medium containing 6% sucrose for a total of 28 days culture period
      significantly increased shoot regeneration for all four genotypes evaluated.
      Moreover, pre-culture of anthers on medium containing 15% sucrose for 2-7 days
      was sufficient to dramatically reduce the frequency of shoot regeneration from
      somatic tissues and thereby to increase the frequency of microspore-derived
      plants in flax anther culture. Furthermore, replacing 15% sucrose with 6% sucrose
      and 9% polyethylene glycol (PEG), or 3% sucrose and 12% PEG, in pre-culture
      medium did not significantly affect callus induction and shoot regeneration. The
      results indicate that sucrose may act as carbon/energy source as well as an
      osmotic regulator in flax anther culture. Sucrose as an osmotic regulator may be
      replaced by a non-metabolizable osmoticum: PEG. The implication of this study in
      flax anther culture and breeding is discussed.

PMID- 15235815
TI  - Association of CYP17 gene polymorphism and rheumatoid arthritis in Chinese
      patients in central Taiwan.
AB  - We investigated whether there is an association between polymorphism of the CYP17
      gene and rheumatoid arthritis in Chinese patients in central Taiwan. Genomic DNA
      was extracted from the peripheral blood of 146 female and 47 male RA patients, as
      well as from 42 female and 59 male control subjects; restriction fragment length
      polymorphism (defined as the A1 and A2 alleles) was then determined. Clinical
      variables such as rheumatoid factor positivity, extra-articular manifestations,
      and joint erosion were also investigated for the RA patients. We found that more
      male RA patients had the A1 allele (P=0.019) and fewer female RA patients the A2
      allele than control subjects (P=0.048). In male RA patients, A1 carriers showed
      more extra-articular manifestations (P=0.048). In female patients, a significant
      decrease in A2 carriers mainly occurred in the later-onset age group (P=0.024).
      This study suggests that the A2 allele may significantly decrease the overall
      risk of developing RA. In women, the protective effect of A2 mainly affects the
      older age group. In men, the clinical severity of RA may decrease in patients
      with the A2/A2 genotype.

PMID- 15235816
TI  - Effect of viscoelastic relaxation on moisture transport in foods. Part I:
      solution of general transport equation.
AB  - Within the framework of continuum mechanics, Singh et al. developed an integro
      differential equation, which applies to both Darcian (Fickian) and non-Darcian
      (non-Fickian) modes of fluid transport in swelling biological systems. A
      dimensionless form of the equation was obtained and transformed from moving
      Eulerian to the stationary Lagrangian coordinates. Here a solution scheme for the
      transport equation is developed to predict moisture transport and viscoelastic
      stresses in spheroidal biopolymeric materials. The equation was solved
      numerically and results used for predicting drying and sorption curves, moisture
      profiles, and viscoelastic stresses in soybeans. The Lagrangian solution was
      obtained by assembling together several schemes: the finite element method was
      used to discretize the equation in space; non-linearity was addressed using the
      Newton-Raphson method; the Volterra term was handled via a time integration
      scheme of Patlashenko et al. and the Galerkin rule was used to solve the time
      differential term. The solution obtained in Lagrangian coordinates was
      transformed back to the Eulerian coordinates. In part II of this sequence we
      present the numerical results.

PMID- 15235817
TI  - Effect of viscoelastic relaxation on moisture transport in foods. Part II:
      sorption and drying of soybeans.
AB  - The general fluid transport equation presented in Part-I of this paper is used
      for predicting moisture transport and viscoelastic stresses during sorption and
      drying of soybeans. Predicted drying curves were validated using experimental
      data obtained from literature (average absolute difference 6-13%). For drying
      temperatures used in the soybean processing industry (70-93 degrees C), smooth
      moisture profiles were obtained, which indicated Fickian (Darcian) transport. As
      the drying temperature approached the glass transition temperature (25 degrees C
      at 10% moisture content), the moisture profiles became sharper, which indicated
      non-Fickian (non-Darcian) transport. The viscoelastic stress profiles clearly
      exhibited the role of the force terms during imbibition and drying. Increase in
      drying temperature tends to decrease the stress relaxation function but reduction
      in moisture content during drying tends to increase it. The increase in stress
      due to the reduction in moisture content below 10% was not compensated by an
      increase in drying temperature. Drying of soybeans below 10% moisture content
      should be avoided in the industry because this will lead to thicker flakes that
      reduce the amount of oil recovery. During imbibition of soybeans, a high
      magnitude of stresses was obtained in the rubbery regions, which may cause
      critical regions prone to fissuring. The role of glass transition on stress
      development and critical region development was clearly observed during drying
      and imbibition of soybeans.

PMID- 15235818
TI  - Dynamical consequences of harvest in discrete age-structured population models.
AB  - The role of harvest in discrete age-structured one-population models has been
      explored. Considering a few age classes only, together with the overcompensatory
      Ricker recruitment function, we show that harvest acts as a weak destabilizing
      effect in case of small values of the year-to-year survival probability P and as
      a strong stabilizing effect whenever the survival probability approaches unity.
      In the latter case, assuming n = 2 age classes, we find that harvest may transfer
      a population from the chaotic regime to a state where the equilibrium point (
      x(1)*, x(2)*) becomes stable. However, as the number of age classes increases
      (which acts as a stabilizing effect in non-exploited models), we find that
      harvest acts more and more destabilizing, in fact, when the number of age classes
      has been increased to n = 10, our finding is that in case of large values of the
      survival probabilities, harvest may transfer a population from a state where the
      equilibrium is stable to the chaotic regime, thus exactly the opposite of what
      was found in case of n = 2. On the other hand, if we replace the Ricker relation
      with the generalized Beverton and Holt recruitment function with abruptness
      parameter larger than 2, several of the conclusions derived above are changed.
      For example, when n is large and the survival probabilities exceed a certain
      threshold, the equilibrium will always be stable.

PMID- 15235819
TI  - The effect of ureteric stents on urine flow: reflux.
AB  - If the ureter becomes blocked, the resultant increased pressure may be relieved
      by inserting a double-J stent (a polymer tube, usually punctuated with holes). A
      major clinical problem associated with stent use is reflux (retrograde flow of
      urine from the bladder to the kidney), which may result in infections, scarring,
      and even renal failure. We develop a mathematical model, treating the ureter as
      an elastic tube and the stent as a permeable rigid tube within it. We investigate
      how the number of holes in the stent wall affects the total amount of reflux that
      occurs when bladder pressure rises, by considering the limits of a highly
      permeable stent, and an impermeable stent. We find that, in the scenarios we
      consider, the highly-permeable stent gives rise to less total reflux than the
      impermeable one.

PMID- 15235820
TI  - Thresholds for macroparasite infections.
AB  - We analyse here the equilibria of an infinite system of partial differential
      equations modelling the dynamics of a population infected by macroparasites. We
      find that it is possible to define a reproduction number R(0) that satisfies the
      intuitive definition, and yields a sharp threshold in the behaviour of the
      system: if R(0) < 1, the parasite-free equilibrium (PFE) is asymptotically stable
      and there are no endemic equilibria; if R(0) > 1, the PFE is unstable and there
      exists a unique endemic equilibrium. The results mainly confirm what had been
      obtained in simplified models, except for the fact that no backward bifurcation
      occurs in this model. The stability of equilibria is established by extending an
      abstract linearization principle and by analysing the spectra of appropriate
      operators.

PMID- 15235821
TI  - A randomized cross-over trial to determine the effect of Cremophor EL on the
      pharmacodynamics and pharmacokinetics of carboplatin chemotherapy.
AB  - PURPOSE: Paclitaxel, when combined with carboplatin, exhibits a platelet-sparing
      effect. Paclitaxel is formulated in Cremophor EL (CrEL), which has been shown in
      preclinical models to reduce haematological toxicity from radiotherapy and
      chemotherapy. We sought to determine the effect of a 3-h infusion of 20 ml/m2
      (equivalent to 175 mg/m2 paclitaxel) CrEL on myelosuppression following
      carboplatin chemotherapy, and the effect of CrEL on carboplatin pharmacokinetics.
      METHODS: A total of 16 patients with locally advanced or metastatic cancer were
      randomized to receive either CrEL or saline over 3 h prior to carboplatin (area
      under the curve, AUC, 5-7). Each patient was subsequently crossed over to the
      other treatment. Blood samples were collected at selected time-points for
      estimation of platinum AUC and 24-h platinum levels. Full blood counts were
      obtained three times per week. RESULTS: Of the 16 patients randomized, 15 were
      evaluable. Myelosuppression was measured by percentage fall at nadir and nadir
      levels. No significant differences were obtained when comparing CrEL and saline
      with respect to the above end-points after adjusting for multiple testing. There
      was no evidence to indicate that CrEL altered the pharmacokinetics of
      carboplatin. CONCLUSION: CrEL at this dose and schedule does not appear to be a
      major contributory factor to the platelet-sparing effect of paclitaxel when
      combined with carboplatin, nor does it alter the pharmacokinetics of carboplatin.

PMID- 15235822
TI  - Cyclooxygenase inhibitors and thalidomide ameliorate vincristine-induced
      hyperalgesia in rats.
AB  - In this study ibuprofen (50.0 mg/kg, i.p.), rofecoxib (10.0 mg/kg, i.p.) and
      thalidomide (50.0 mg/kg, oral) were shown to prevent vincristine-induced
      mechanical hyperalgesia. Sprague-Dawley rats were injected every other day with
      vincristine (0.1 mg/kg) over 13 days. The animals were cotreated daily with
      vehicle (saline), ibuprofen, rofecoxib or thalidomide throughout the period of
      vincristine treatment. Mechanical withdrawal threshold to punctuate and radiant
      heat stimuli were determined prior to and then on alternate days throughout the
      treatment period. Vincristine vehicle-treated animals developed marked mechanical
      hyperalgesia from day 5 of chemotherapy and this lasted until the end of the
      experiment. Thermal thresholds were not altered by the administration of
      vincristine vehicle. Animals in the vincristine vehicle group neither gained nor
      lost weight during the treatment period. All three active drugs showed an
      antihyperalgesic effect on the responses to mechanical stimulation of the hind
      paw that was significant from day 5 for ibuprofen and thalidomide and from day 7
      for rofecoxib. Thermal thresholds increased after the administration of both the
      NSAIDs and thalidomide. Rofecoxib was the only drug to show any beneficial effect
      in protecting the animals from failure to gain body weight.

PMID- 15235823
TI  - Therapeutic efficacy of multimodal combination therapy using transcatheter
      arterial infusion of epirubicin and cisplatin, systemic infusion of 5
      fluorouracil, and additional percutaneous ethanol injection for unresectable
      hepatocellular carcinoma.
AB  - PURPOSE: Previous studies have shown that a treatment regimen using epirubicin,
      cisplatin, and 5-fluorouracil (5-FU) (ECF) has a survival benefit for gastric
      cancer patients. Based on these results and the hypothesis that a combination
      modality has a better therapeutic advantage over a single mode of therapy, the
      efficacy of multimodal combination therapy using a transarterial infusion of
      epirubicin and cisplatin, systemic infusion of 5-FU, and additional percutaneous
      ethanol injection (PEI) for unresectable hepatocellular carcinoma (HCC) was
      investigated in this study in comparison with conventional transarterial
      chemoembolization (TACE). PATIENTS AND METHODS: From July 1997 to September 1998,
      a total of 52 patients with unresectable HCC who underwent at least two cycles of
      transarterial chemotherapy were enrolled in this study. Among the 52 patients, 30
      (ECF group) received a multimodal combination therapy comprising transarterial
      infusion of epirubicin (50 mg/m2) and cisplatin(60 mg/m2), systemic infusion of 5
      FU (200 mg/m2), and additional PEI every 4 weeks, and the remaining 22(ADR group)
      received conventional TACE using Adriamycin (ADR, 50 mg) and Gelfoam every 8
      weeks. RESULTS: During the follow-up period (mean 13.8 +/ -8.5 months), the
      objective tumor response of the ECF group was significantly higher than that of
      the ADR group (53.3 vs 22.7%, P=0.044). The median survival time was 13.5 months
      for the ECF group and 10.5 months for the ADR group (P=0.026). The cumulative
      survival rates at 6, 12, 18, and 24 months,respectively, were 90, 57, 27, and 17%
      for the ECF group and 73, 37, 7, and 0% for the ADR group. Uni-variate analysis
      showed five prognostic factors including tumor number, tumor morphology, portal
      vein thrombosis, Child-Pugh classification, and tumor response. With multivariate
      analysis, portal vein thrombosis and tumor response were identified as the two
      independent f actors for survival. No serious adverse effect was observed in the
      ECF group, while there was a higher tendency for hepatic complications in the ADR
      group. CONCLUSIONS: Combination therapy comprising transarterial infusion of
      epirubicin and cisplatin, systemic infusion of 5-FU, and additional PEI appears
      to be feasible and promising as a multimodal approach for unresectable HCC.
      Furthermore, it may provide a survival benefit for patients with more advanced
      disease.

PMID- 15235824
TI  - A phase I trial of pharmacokinetic modulation of carboxyamidotriazole (CAI) with
      ketoconazole in patients with advanced cancer.
AB  - PURPOSE: Carboxyamidotriazole (CAI) is a novel antineoplastic agent in clinical
      development with limited oral bioavailability. In vitro, ketoconazole has been
      demonstrated to inhibit CYP3A4-mediated metabolism of CAI. We performed this
      phase I trial to determine if ketoconazole-mediated CYP3A4 inhibition would lead
      to favorable alteration of CAI pharmacokinetics, and to evaluate the safety,
      toxicity and tolerability of the proposed combination. DESIGN: Forty-seven
      patients were treated using a standard three patients per cohort CAI dose
      escalation scheme. In cycle 1, CAI was administered alone on day-6 followed by a
      single dose of ketoconazole (200 mg) on day 0. CAI and ketoconazole (200 mg/day)
      were subsequently coadministered on days 1 and 3-28. Plasma samples for
      pharmacokinetic analysis were obtained following the doses on days-6 and 1. All
      subsequent cycles were of 28-day duration, and consisted of daily CAI and
      ketoconazole coadministration. RESULTS: Pharmacokinetic analysis was performed on
      samples from 44 patients. In most patients administration of ketoconazole
      produced an increase in CAI AUC and Cmax with a decrease in CAI clearance. Seven
      patients experienced stable disease for up to 12 months. Gastrointestinal and
      constitutional toxicities were the most common toxicities. CONCLUSIONS:
      Coadministration of CAI with ketoconazole increased CAI exposure in most of the
      patients without altering the toxicity profile of CAI. The highest CAI dose
      administered on the trial was 300 mg/day. The clinical utility of such a
      modulation strategy might be explored in future clinical trials of CAI.

PMID- 15235825
TI  - Vascular responses to hypercapnia in anesthetized dogs.
AB  - To evaluate the vascular responses to systemic acute mild hypercapnia (Pa(CO)(2)
      = 65 mmHg), we determined the vascular compliance with the relation between the
      change in circulating blood volume and the change in central venous pressure
      during and after fluid infusion in dogs anesthetized with halothane in
      normocapnia and hypercapnia. Circulating blood volume was measured continuously
      by (51)Cr-labeled erythrocyte dilution method together with hemodynamic
      variables. Small reduction in vascular compliance (8.1 +/- 1.0 ml.mmHg(-1).kg(-1)
      in normocapnia, 5.8 +/- 0.5 ml.mmHg(-1).kg(-1) in hypercapnia), large reduction
      in delayed compliance, which were quantitated by computer simulation using
      Maxwell's viscoelastic model, and significant increase in blood volume in central
      circulation were observed in hypercapnia. The essential change in hypercapnia was
      concluded as the vasoconstriction in capacitance vessels. Simultaneously, the
      reduction of total peripheral resistance (1.09 +/- 0.08 mmHg.min.kg.ml(-1) in
      normocapnia, 0.98 +/- 0.07 mmHg.min.kg.ml(-1) in hypercapnia) with no change in
      transvascular filtration coefficient (0.14 +/- 0.02 ml.mmHg(-1).min(-1).kg(-1))
      suggests the increase in shunt flow in peripheral circulation.

PMID- 15235826
TI  - Continuous infusion of vecuronium in children.
AB  - The average dose of vecuronium required in children continuous infusion to attain
      a steady state block of 90% was determined. The electromyographic (EMG) response
      and mechanical response to supramaximal stimulation of the ulnar never recorded
      simultaneously, were significantly correlated in four children. The steady-state
      infusion rate requirement of vecuronium was 1.4 +/- 0.03 micro g/kg/min during 2%
      enflurane anesthesia and 3.1 +/- 0.03 micro g/kg/min during 1% halothane
      anesthesia. The spontaneous recovery time to 25% of the control by EMG during
      halothane and enflurane anesthesia was 12.6 +/- 1.1 and 10.3 +/- 1.5 min,
      respectively, after termination of the infusion. There was no cumulative effect
      after prolonged vecuronium infusion.

PMID- 15235827
TI  - Effects of volatile anesthetics on cardiac metabolism in the low-pressure
      perfused rat heart.
AB  - Effects of halothane, enflurane and isoflurane on the myocardial metabolism were
      studied in the rat heart-lung preparation. Hearts were perfused at a low
      perfusion pressure (SBP 50 mmHg, DBP 30 mmHg) with succinate or glutamate as
      substrates. Thirty minutes after the perfusion, intramyocardial ATP, pyruvate,
      lactate and glycogen were measured enzymatically. Although there was no
      significant difference in ATP levels of hearts with either substrate, and whether
      or not volatile anesthetics were present, 1% halothane and 1.5% isoflurane
      reduced the L/P ratio when succinate was substrate (24.46 +/- 4.81, 17.68 +/-
      9.10 vs 39.82 +/- 10.83), and 2% enflurane decreased it when glutamate was
      substrate (22.25 +/- 10.99 vs 38.44 +/- 6.55). The glycogen levels in volatile
      anesthetics groups were lower than control when succinate was substrate. The
      improvement of energy demand-supply balance by inhalation anesthetics may be
      stronger than their inhibition of electron transport in mitochondria under
      certain ischemic conditions.

PMID- 15235828
TI  - Effect of preanesthetic famotidine on gastric volume and pH.
AB  - The effect of preanesthetic 20 mg of famotidine on gastric fluid volume and pH
      were studied in patients scheduled for elective surgery. One hundred and twenty
      eight patients were divided into four groups-control, intravenous, intramuscular
      and oral with 32 patients in each group. Patients in placebo group received no
      famotidine and served as control. Patients in the intravenous and intramuscular
      groups were administered famotidine one hour before surgery. Patients in the oral
      group were administered famotidine the night before and on the morning of
      surgery. Gastric volume in the control group was 19.1 +/- 10.8 ml; in the
      intravenous group, 7.4 +/- 6.4 ml; in the intramuscular group, 7.3 +/- 6.9 ml;
      and in the oral group, 7.1 +/- 6.9 ml. Gastric pH was 3.4 +/- 2.3, 6.8 +/- 1.1,
      6.9 +/- 1.6, and 6.7 +/- 1.2 in groups one through four, respectively. When
      compared to the control group, famotidine significantly decreased gastric volume
      and increased gastric pH. There were no statistical differences among the
      different modes of administration. No adverse effects were observed in this
      study. It is concluded that preanesthetic management of 20 mg of famotidine
      reduced the risk of acid aspiration pneumonitis.

PMID- 15235829
TI  - Analgesic dose-response relation in cervical epidural block.
AB  - The relationship between the age and the spread of analgesia from different
      epidural anesthetic doses was examined by studying analgesic dose responses in
      cervical epidural analgesia. Two different anesthetic doses (5 ml or 10 ml) of 2%
      mepivacaine were injected into the cervical epidural space at a constant pressure
      (80 mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick
      was assessed. The significant correlation was found between the patient's age and
      the number of spinal segments blocked (5 ml : r = 0.8498, P < 0.01, 10 ml : r =
      0.5988, P < 0.01). The inverse linear relationship was found between the
      patient's age and the segmental dose requirement (5 ml : r = -0.6754, P < 0.01,
      10 ml : r = -0.5784, P < 0.01). Patients under 39 years of age showed a direct
      relationship between the dose injected and the number of spinal segments blocked,
      enabling prediction of the number of segments blocked with a given dose of local
      anesthetic. Doubling the epidural dose approximately doubled the number of spinal
      segments blocked. The analgesic dose-response relation in patients over 60 years
      of age differed from that in patients under 39 years of age and doubling the
      epidural dose did not double the number of spinal segments blocked. Progressively
      more extensive analgesia was obtained from a given dose of local anesthetic with
      advancing age. It was difficult to limit the extent of analgesia by injecting a
      smaller dose of local anaesthetic in the elderly.

PMID- 15235830
TI  - The effect of verapamil on halothane-epinephrine or digitalis-induced ventricular
      dysrhythmias in dogs.
AB  - The effect of verapamil on ventricular dysrhythmias was evaluated using two
      canine models. In one model, ventricular dysrhythmias were induced by 1%
      halothane-epinephrine (1.5 approximately 30 micro g/kg/min.) in 20 dogs (Group
      I). In the other model, ventricular dysrhythmias were induced by digoxin (0.1
      approximately 0.2 mg/kg) in 27 dogs (Group II). Verapamil (0.2 approximately 0.5
      mg/kg) was given to treat these ventricular dysrhythmias. When verapamil was
      ineffective, lidocaine (1 approximately 2 mg/kg) was given following the
      administration of verapamil. In 7 dogs of group II, lidocaine alone was given.
      Verapamil was effective in 16 animals of group I, and in 10 animals of group II.
      Lidocaine was ineffective in the remaining 4 of group I, whereas effective in the
      remaining 17, including those given lidocaine alone of group II. From these
      findings, it was inferred that Ca(2+) dependent abnormal automaticity and/or re
      entry may be more closely related to the genesis of halothane-epinephrine-induced
      ventricular dysrhythmias refractory to lidocaine, whereas triggered activity may
      be more closely related to that of digitalis-induced ventricular dysrhythmias. In
      conclusion, verapamil was more effective against halothane-epinephrine-induced
      ventricular dysrhythmias than against digitalis-induced ventricular dysrhythmias.

PMID- 15235831
TI  - Effects of carboxyhemoglobin on pulse oximetry in humans.
AB  - Carboxyhemoglobin (HbCO)-induced reading errors of the Biox 3700 (version J,
      Ohmeda) pulse oximeter were determined in 6 healthy volunteers rendered hypoxic
      (Sa(O)(2) from 65-100%) by breathing mixtures of air in nitrogen. The oximeter
      reading (Sp(O)(2)) before and after cigarette smoking was compared with
      oxyhemoglobin percentage (%HbO(2)). Mean HbCO levels were; 3.0 +/- 1.0 (SD) %
      before cigarette smoking and 5.2 +/- 1.7% after smoking, whereas mean
      methemoglobin was unchanged as 0.5 +/- 0.1%. The correlations of the Sp(O)(2) (y)
      with %HbO(2) (x) were; y = 1.01x - 0.30 (r = 0.990, n = 21, P < 0.001) when %HbCO
      was less than 2.5, and y = 1.01x + + 3.21 (r = 0.964, n = 33, P < 0.001) when
      %HbCO was above 5.0%. The reading error, (Sp(O)(2) - %HbO(2)), could be expressed
      as a function of %HbCO; 1.06 x %HbCO(2) - 2.49 (r = 0.669, n = 83, P < 0.05).
      Thus, the Sp(O)(2) is approximately the sum of %HbCO(2) and (%HbCO - 2.5), and
      overestimates %HbO(2) in the high levels of HbCO. The pulse oximeter should be
      used with caution in patients with the elevated level of %HbCO.

PMID- 15235832
TI  - The effect of human SOD on the survival rate in rats with temporary splanchnic
      ischemia.
AB  - The accumulation of oxygen free radicals is reported to occur in the organs
      subjected to temporary ischemia followed by reperfusion, resulting in the fatal
      outcome of the animals. The effects of human SOD, a representative scavenger of
      oxygen free radicals, on the survival rates were investigated in the rats with
      temporary splanchnic ischemia. The temporary ischemia was induced by the
      occlusion of anterior mesenteric and celiac arteries for 30 min under anesthesia.
      Prior and after treatment with 2 mg/100 g of human SOD, iv or sc, produced
      significant improvements in survival rates. Human SOD, cloned from human placenta
      DNA and expressed in microorganisms, has extreme homogeneity. The results suggest
      the possible introduction of human SOD into clinical field as an effective
      scavenger of oxygen free radicals.

PMID- 15235833
TI  - Tracheal dilatation by halothane and enflurane in man.
AB  - The effect of halothane and enflurane on tracheal tone were studied in 21
      patients during the induction of anesthesia. Endotracheal tube cuff pressure was
      used to measure tracheal tone. Anesthesia, maintained by nitrous oxide 70% in
      oxygen, was supplimented with succinylcholine drip infusion to immobilize the
      patient. Ventilation was controlled by a Volume-preset ventilator. In the
      halothane group, the initial cuff pressure was 14.8 +/- 1.3 (mean +/- SE) cmH(2)O
      but 10 min after 0.15 mg/kg of pancuronium injection, it increased to 21.7 +/-
      2.3 cmH(2)O (control). Ten min after inhalation of 0.75% of halothane, cuff
      pressure decreased to 14.7 +/- 2.3 cmH(2)O (34 +/- 11% decrease from the control
      value). In the enflurane group, the initial cuff pressure was 17.6 +/- 1.8
      cmH(2)O and it increased to 21.0 +/- 1.7 cmH(2)O (control) 10 min after
      pancuronium injection. Ten min after 1.7% of enflurane inhalation, cuff pressure
      decreased to 17.1 +/- 2.3 cmH(2)O (23.9 +/- 6% decrease from the control value).
      Halothane and enflurane produced similar tracheal dilatation in healthy
      individuals.

PMID- 15235834
TI  - Interaction between diltiazem and halothane or enflurane in the canine blood
      perfused papillary muscle and sinoatrial node preparations cross-circulated by
      chronically instrumented conscious donor dog.
AB  - Interaction of cardiovascular effects of diltiazem with those of halothane or
      enflurane was estimated in the canine isolated papillary muscle and sinoatrial
      node preparations perfused by arterial blood of the chronically instrumented
      conscious and halothane- or enflurane-anesthetized donor dog, into which
      diltiazem was infused i.v. at a rate of 20 micro g/kg/min for 60 min. One hour
      after diltiazem infusion, in the conscious donor dog, mean arterial pressure
      (MAP) and heart rate (DHR) were decreased to 84 +/- 3 and 84 +/- 2% and PQ
      interval (PQ) was prolonged to 148 +/- 5%, while in the isolated preparations,
      developed tension (DT) of the papillary muscle and sinoatrial rate (SAR) were
      decreased to 68 +/- 3 and 74 +/- 3% and blood flow (BF) was increased to 155 +/-
      5% (n = 10). On the other hand, halothane (0.8%) anesthesia per se decreased MAP,
      DHR, DT and SAR to 89 +/- 8, 84 +/- 3, 79 +/- 3 and 89 +/- 5% (n = 7) of each
      basal value in conscious state 20 min after the inhalation. During halothane
      anesthesia, the same dose of diltiazem infused decreased MAP to 74 +/- 4 (n = 7),
      DHR to 66 +/- 4 (n = 6), DT to 62 +/- 7 (n = 7) and SAR to 69 +/- 1% (n = 3) of
      each value suppressed by halothane itself. Meanwhile, enflurane (1.7%) anesthesia
      itself decreased MAP, DHR, DT and SAR to 81 +/- 3, 85 +/- 2, 81 +/- 2 and 88 +/-
      2% (n = 10) of each basal value in conscious state 30 min after enflurane
      inhalation. During enflurane anesthesia diltiazem decreased MAP to 74 +/- 3 (n =
      10), DHR to 67 +/- 3 (n = 8), DT to 45 +/- 5 (n = 10) and SAR to 74 +/- 6% (n =
      3) of each value under enflurane anesthesia alone. PQ interval of the donor dog
      heart was prolonged by halothane alone to 111 +/- 5% (n = 7) and by enflurane
      alone to 110 +/- 2% (n = 10) of the value before each anesthesia, and then
      diltiazem prolonged PQ interval to 160 +/- 8% (n = 6) and 174 +/- 10% (n = 8) of
      each value suppressed by the anesthetic itself during halothane- or enflurane
      anesthesia, respectively. The second degree AV conduction block was induced in 1
      of 7 halothane- and in 2 of 10 enflurane-anesthetized donor dogs, respectively.
      The sinus arrest was induced by diltiazem in 4 of 7 sinoatrial node preparations
      under halothane and in 7 of 10 ones during enflurane anesthesia. Moreover, plasma
      concentration of diltiazem 60 min after the start of infusion was 556 +/- 121
      ng/ml in conscious dogs and tended to increase to 752 +/- 101 ng/ml in enflurane
      anesthetized donor dogs (n = 4), but there was no significant difference between
      two values (0.05 < P < 0.1). These results indicate that effects of diltiazem
      could be potentiated during halothane or enflurane anesthesia by elimination of
      compensatory reflex noted in conscious state, and that the negative inotropic
      effect of diltiazem was enhanced by enflurane anesthesia due to unknown
      mechanisms which probably include a slight but insignificant increase in plasma
      concentration.

PMID- 15235835
TI  - The comparative cardiovascular effects of sevoflurane with halothane and
      isoflurane.
AB  - Using closed chest dogs, the cardiovascular effects of sevoflurane were compared
      with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5
      and 3.0 MAC. They were evaluated by the changes of arterial blood pressure,
      central venous pressure, pulmonary artery pressure, maximum rate of left
      ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood
      flow. The suppression of left cardiac function by sevoflurane was less than that
      of halothane, but was greater than that of isoflurane. Heart rate, systemic
      vascular resistance with sevoflurane were slightly lower than that of
      isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were
      significantly ( P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane.
      There was no significant difference on coronary sinus flow between sevoflurane
      and isoflurane. The depth of anesthesia could be quickly changed by adjustment of
      inspired sevoflurane concentration in comparison with the other two anesthetics.

PMID- 15235836
TI  - The effect of RO15-1788 on cardiovascular depression caused by fentanyl and
      diazepam.
AB  - Cardiovascular depression occurring when diazepam is combined with fentanyl has
      been investigated using the benzodiazepine antagonist RO15-1788 in the dog. After
      the initial administration of fentanyl (40 mcg/kg), the mean arterial pressure
      (MAP) decreased to 89% of its control value. Following the administration of
      diazepam (1.2 mg/kg), the MAP and the total peripheral resistance (TPR) decreased
      significantly, to 75% and 83% of their control values respectively. After the
      administration of RO15-1788 (0.4 mg/kg), the MAP increased significantly to 90%
      and the TPR to 102% of their control values and, lastly, the administration of
      naloxone (40 mcg/kg) increased the MAP to 108% of its control value. No
      relationship was found between the changes in the catecholamines and the changes
      in the MAP after the administration of fentanyl, diazepam, and RO15-1788. The
      mechanism of circulatory depression when diazepam was used with fentanyl is
      interpreted as being a peripheral vasodilatory effect of diazepam acting by way
      of the benzodiazepine receptors since RO15-1788 was found to antagonize this
      effect.

PMID- 15235837
TI  - The effects of ulinastatin on the reticuloendothelial system (RES) of rabbits in
      endotoxin shock.
AB  - Carbon clearance, concentration of fibronectin (Fn) in the blood and arterial
      ketone body ratio (AKBR) have been measured in the rabbit in order to evaluate
      the RES phagocytic activity and the effect of ulinastatin on it in endotoxin (ET)
      shock. The following results were obtained: 1) carbon deposition by ET injection
      was found in organs (lung and kidney) which did not show it in the control group.
      The reasons for this might be considered that the RES was blocked because of
      phagocytizing ET and tissue debris, so that the carbon which could not be
      processed by the RES spilled over and became clogged; 2) the RES phagocytic
      activity were found to decline from an early stage after injection of a lethal
      dose of ET due to a decline in Fn productivity and an increase in Fn consumption;
      and, 3) ulinastatin suppressed the decrease of Fn and the carbon deposition in
      the kidney in ET shock. These results are suggestive of the usefulness of
      ulinastatin as an anti-shock agent, preserving the RES phagocytic activity
      through the inhibition of Fn consumption.

PMID- 15235838
TI  - Requirement for accuracy of pulse-oximeters in high oxygen.

PMID- 15235839
TI  - Epidurally administered halothane vapor potentiates mepivacaine-induced epidural
      anesthesia: a report of 10 cases.

PMID- 15235840
TI  - A clinical trial of sevoflurane in children for herniorrhaphy.

PMID- 15235841
TI  - Spinal anesthesia with pentazocine for total abdominal hysterectomy.
AB  - Intraspinal pentazocine, 1.5 mg/kg, produced sufficient analgesia and moter block
      in 50 cases of abdominal total hysterectomy. Pentazocine, a derivative of
      benzomorphans, shares some common characteristics with local anesthetics in the
      chemical structure. Both agents have an aromatic ring and an intermediate chain,
      in common, which connects the former to nitrogen moiety, and the local anesthetic
      action was anticipated. The onset of the sensory block was 3.2 +/- 0.9 (mean +/-
      SD) min, and the maximum level was T10 and T4 with mean level of T6. The onset of
      motor weakness at the knee was 4.1 +/- 1.9 min, and the duration was 108 +/- 10.5
      min.

PMID- 15235842
TI  - Malposition of central venous catheter.

PMID- 15235843
TI  - Extended axillary block (E. A. B.).

PMID- 15235844
TI  - The minimum alveolar concentration of sevoflurane in cats.
AB  - Eight adult cats of either sex were studied. The minimal alveolar concentration
      (MAC) for sevoflurane in the cats was found to be 2.58 +/- 0.30% (mean +/- SD).
      The ratios of MAC values between sevoflurane and halothane, enflurane and
      isoflurane in cats were very similar to those ratios found in humans and dogs.
      This observation suggests that the results of this study are correct and allows
      us to estimate unknown MAC values for sevoflurane in other species using known
      MAC values for other anesthetic agents.

PMID- 15235845
TI  - The central nervous stimulating effect of four different halogenated ether
      anesthetics and halothane in mice.
AB  - Although enflurane is a convulsive anesthetic, its structural isomer, isoflurane,
      is believed not to be. We reported previously that, unexpectedly, isoflurane more
      frequently produced opisthotonus in young mice, especially during the induction
      period, than enflurane. In the present study, we examined the incidences of
      opisthotonus induced by four halogenated ether anesthetics and halothane to
      evaluate their CNS stimulating actions. As experimental animals, we used young
      male mice, with another two aged groups of male mice to clarify the relationship
      of the incidence of opisthotonus to aging. The percentage incidence of
      opisthotonus was 93% for sevoflurane, 81% for isoflurane, 64% for enflurane, 17%
      for methoxyflurane and 2% for halothane. These results suggest that the
      halogenated ether anesthetic, which is rapidly uptaken by the CNS during
      induction, is more likely to produce CNS stimulation, subsequently leading to
      opisthotonus. There was no age related susceptibility difference to anesthetic
      induced opisthotonus, except for enflurane, in which the incidence of
      opisthotonus was higher in the aged group.

PMID- 15235846
TI  - Fifty percent nitrous oxide depresses recovery from anoxic heart failure induced
      by 100% nitrous oxide.
AB  - In experiments on an isolated rate heart lung preparation, the effects of 100%
      oxygen, 50% nitrous oxide or air on myocardial metabolism during recovery from
      anoxic heart failure were evaluated with intramyocardial high energy phosphates,
      lactate and glycogen. A hundred percent nitrous oxide was administered until the
      cardiac output decreased from 30 to 20 ml/min, and then 50% nitrous oxide, air or
      100% oxygen was administered. Fifty percent nitrous oxide reduced the cardiac
      output and caused heart failure again. The ATP level and energy charge in hearts
      with 50% nitrous oxide were significantly lower than those in the others. These
      data indicate that 50% nitrous oxide during recovery from anoxic heart failure
      had deleterious effects on myocardial function and metabolism.

PMID- 15235847
TI  - Contribution of arterial redox potential measurement to the care of critically
      ill patients.
AB  - 175 arterial and 122 urinary samples from 20 patients admitted in ICU for organ
      system failure (OSF) were analysed. Besides arterial blood gases and lactate,
      electrolyte concentrations, pH, rH2 and specific resistance (R) in blood and
      urine were measured. Redox potential (E) and base excess were calculated from
      these data. Patients were defined as having MOSF if their organ systems met
      failure criteria during their ICU stay. Data were classified with corresponding
      number of OSF developed in the patients when samples were obtained. Acid-base
      balance or base excess alone could not be used to predict the severity of illness
      as assessed by increasing number of organ system failures. Significant elevations
      in blood lactate concentrations were observed only in patients with four, five or
      six OSF. A lack of correlation between blood lactate and severity of OSF
      indicates that blood lactate is not valid as a guide to ultimate outcome of the
      patients. Arterial redox potentials progressively decreased with increasing
      number of OSF, therefore, it can be stated that the serial measurements of
      arterial redox potential are useful in assessing the patient's status or
      predicting their ultimate outcome.

PMID- 15235848
TI  - The effects of verapamil on cerebrospinal fluid pressure in surgical patients.
AB  - The effects of verapamil upon cerebrospinal fluid pressure (CSFP) were studied in
      twenty surgical patients without intracranial pathology who were divided into two
      groups of ten patients each: verapamil 0.075 mg.kg(-1) was given in group 1 and
      0.15 mg.kg(-1) was given in group 2. A spinal needle was inserted into the
      subarachnoid space to permit continuous measurement of CSFP. Intravenous
      verapamil as a bolus produced a statistically significant increase in CSFP: from
      6.0 +/- 3.5 (mean +/- SD) to 10.5 +/- 4.3 mmHg in group 1 ( P < 0.01), and from
      6.2 +/- 3.1 to 12.6 +/- 3.8 mmHg in group 2 ( P < 0.01). CSFP after verapamil
      attained its maximum in 0.5-1.5 min, then gradually returned to control levels.
      Changes in CSFP were always associated with statistically significant decreases
      in arterial blood pressure and cerebral perfusion pressure, while the heart rate
      showed variable changes. It is concluded that a clinical dose of verapamil showed
      variable changes. It is concluded that a clinical dose of verapamil (0.075-0.15
      mg.kg(-1)) has no neurological side effects in patients without intracranial
      hypertension. However, it must be emphasized that verapamil may increase CSFP to
      undesirable levels and should be avoided in patients with compromised
      intracranial compliance.

PMID- 15235849
TI  - Postanesthetic respiratory depression in humans: a comparison of sevoflurane,
      isoflurane and halothane.
AB  - The postanesthetic respiratory depression with sevoflurane, isoflurane and
      halothane was studied in twenty-one patients. They were divided into three groups
      of seven patients each. One group underwent sevoflurane anesthesia, another group
      isoflurane and the third group halothane. Following extubation, the decrease in
      blood concentration of the anesthetic agent was most rapid with sevoflurane and
      slowest with halothane. Twenty minutes following extubation, resting ventilation
      and ventilatory response to carbon dioxide returned to the preanesthetic state
      with sevoflurane and isoflurane anesthesia. With halothane anesthesia, however,
      the depressive respiratory effects of halothane remained; depressed ventilatory
      response to carbon dioxide, decreased tidal volume and increased respiratory
      frequency. Although halothane has been reported to have the least depressive
      respiratory effect of the three, its elimination was slowest. Thus the
      respiratory effects of halothane persisted up to and past the twenty minute mark,
      far longer than with sevoflurane or isoflurane.

PMID- 15235850
TI  - Venodilator effects of adenosine triphosphate and sodium nitroprusside;
      comparisons during controlled hypotension.
AB  - Adenosine triphosphate as well as sodium nitroprusside has been used for
      hypotensive anesthesia. The purpose of this study was to examine the possibility
      that two hypotensive drugs may exert different effects on venous capacitance
      during controlled hypotension. In rats anesthetized with ketamine, mean arterial
      pressure was lowered to 50 mmHg by intravenous infusion of adenosine triphosphate
      or sodium nitroprusside. Venous capacitance was assessed before and during
      induced hypotension by measuring the mean circulatory filling pressure (MCFP).
      MCFP was measured after briefly arresting the circulation by inflating an
      indwelling balloon in the right atrium. MCFP was lower during adenosine
      triphosphate-induced as well as sodium nitroprusside-induced hypotension as
      compared with the respective value at control (P < 0.01 for adenosine
      triphosphate and sodium nitroprusside). However, the decrease in MCFP by
      adenosine triphosphate (0.8 +/- 0.1 mmHg) was less (P < 0.01) than that by sodium
      nitroprusside (2.3 +/- 0.3 mmHg). These results suggest that at a comparable
      level of arterial hypotension venodilator effect of adenosine triphosphate was
      less than that of sodium nitroprusside. Less venodilatation during adenosine
      triphosphate-induced hypotension may contribute to the maintenance of cardiac
      output during hypotensive anesthesia.

PMID- 15235851
TI  - Plasma fluoride concentration and urinary fluoride excretion in obese and non
      obese patients following enflurane anesthesia.
AB  - Plasma fluoride concentrations and urinary fluoride excretions were measured
      following enflurane anesthesia (1.5%, 2 hours) in obese (8 cases) and non-obese
      (9 cases) patients. At the end of anesthesia, there was no significant difference
      in plasma fluoride concentrations between the two groups. In the several days
      following anesthesia, however, plasma fluoride concentrations in obese patients
      were higher than those in non-obese patients. Urinary fluoride excretions after
      anesthesia were greater in obese patients than those in non-obese patients, and
      the period of increased fluoride excretion was prolonged in obese patients. These
      results suggested that obese patients metabolized more enflurane than non-obese
      patients during the postanesthetic period. In obese patients, their excess fatty
      tissue may cause a greater and more prolonged elevation of blood enflurane
      concentrations after anesthesia.

PMID- 15235852
TI  - A computer program for studying blood gases in respiratory care.
AB  - We developed a computer program in a style of a game to help study blood gases in
      respiratory care. The program generates five simulated patients from a pool of
      11. The player selects one patient, then the program calculates the patient's
      condition according to initial condition and selected treatment. Condition of the
      simulated patient may improve or deteriorate accordingly. Every two hours, the
      program display the data, requests the diagnosis and asks addition/change of
      treatment. The program then judges if diagnosis is correct. This process is
      repeated up to 48 hours. Finally a score and comments are displayed according to
      the performance of the patient and of the player. Students and young physicians
      used the original disk 312 times and more than 30 copies are distributed
      throughout the country. It is useful by itself as a self-teaching tool, but even
      more useful when combined with verbal teaching by instructors.

PMID- 15235853
TI  - Prevention of hypertensive crisis with ATP during anesthesia for pheochromcytoma.
AB  - In the anesthetic management of five patients undergoing excision of
      pheochromocytoma, adenosine triphosphate (ATP) was used for the purpose of
      regulating systemic arterial pressure during the period of tumor manipulation.
      ATP was administered at doses of 0.05-0.4 mg/kg/min. Systemic arterial pressure
      showed a significant decrease from 162 +/- 17/103 +/- 11 mmHg before manipulation
      to 136 +/- 21/81 +/- 10 mmHg during the manipulation period. The plasma
      catecholamine levels showed significant increases in this period. Immediately
      after excision, the systemic arterial pressure was maintained at normal levels
      (118 +/- 13/75 +/- 16 mmHg) by fluid replacement and discontinuation of ATP
      administration, subsequently becoming 129 +/- 19/79 +/- 16 mmHg. The heart rate
      was very stable and tachycardia did not occur during the manipulation period.
      Only one arrhythmic episode occurred in one patient. The systemic vascular
      resistance index was significantly lower during the manipulation period than
      before it. It was therefore considered that ATP was useful as an agent for
      controlling arterial pressure during the anesthesia for pheochromocytoma.

PMID- 15235854
TI  - Epidural pressure and its relation to spread of epidural analgesia.
AB  - The relationships between the epidural pressures following the injection of local
      anesthetic solution and the spread of epidural analgesia were investigated. In 46
      patients, 15 ml of 2% mepivacaine was injected into the lumbar epidural space at
      a constant rate (1 ml/sec) using an electropowered syringe pump. Injection
      pressures and residual pressures were recorded and the spread of analgesia to
      pinprick was assessed. The changes of the epidural pressures during and following
      the injection of a volume of local anesthetic solution in old subjects were
      significantly smaller than those in young subjects (P < 0.05). The spread of
      analgesia closely correlated with the epidural pressures during and following the
      injection of local anesthetic solution. The most close correlation was found
      between the epidural pressure immediately after the completion of injection and
      the spread of analgesia (r = -0.5659, P < 0.001). In conclusion, the lower the
      terminal injection pressure and the residual pressures associated with higher
      age, the wider the spread of epidural analgesia.

PMID- 15235855
TI  - Tracheal tube cuff pressure--study on tube size and inflating gases.
AB  - The effect of nitrous oxide on the cuff pressure was studied from the following
      points of view. One was the size of tubes and the type of cuff. The other was the
      effects of different gas mixture in the cuff. The changes of the cuff pressure
      were investigated using four types of tubes such as the largest standard cuffed
      tube which could be passed through the glottis, the 1.0 mm less in I.D. standard
      cuffed tube, the largest profile cuffed tube, and the 1.0 mm less in I.D. profile
      cuffed tube. There was no difference between the profile cuffed tube groups but
      in the standard cuffed tube groups, the cuff pressure increased from the
      beginning in 1.0 mm less I.D. tube group. Air, inhalation anesthetic gas (nitrous
      oxide:oxygen = 3:2) and mixtured gas (inhalation anesthetic gas and air = 4:3)
      were used to inflate the cuff. The cuff pressure was measured at the same
      patients. In the group of anesthetic gas, the cuff pressure decreased and in some
      cases, there occurred a leakage of gas. In the group of air, the cuff pressure
      increased as well as experiment I. However in the group of mixtured gas, there
      were almost no changes in the cuff pressure. This means that if the cuff is
      inflated with a mixtured gas in which nitrous oxide is under the equivalent
      condition, the cuff pressure would not change.

PMID- 15235856
TI  - A consideration on the new classification of latest lung ventilators.
AB  - Concerning the classification of ventilators, Elam (1958), Faireley (1959), and
      Hunter (1961) reported some simple ones such as pressure limited, volume limited,
      pressure preset, or volume preset models. Mapleson (1969) also classified them by
      the generating force or cycling together with the above-mentioned types. The
      latest ventilators applicable to patients with respiratory failure usually have
      some cut-off function at high airway pressures as a safety measure. Therefore,
      all of them belong to the pressure limited type. Some ventilators are of two
      types such as the time cycled and pressure cycled type. Therefore, we attempted
      to classify ventilators into four groups, i.e. the time cycled, volume cycled,
      pressure cycled and selective time-pressure cycled types according to the
      fundamental mode of ventilator function, the so-called change of cycling from
      inspiration to expiration. Each group was further divided into subgroups
      according to preset dials such as respiratory rate, I/E ratio, inspiration time,
      expiration time, tidal volume, flow rate and airway pressure. By this method,
      fifty one ventilators on the market in Japan can be classified without
      overlapping. Although this classification seems complex, it will be of use in
      selecting ventilators by emphasizing preset dials according to the user's needs,
      ability or both.

PMID- 15235857
TI  - Anesthetic management for implantation of the left ventricular assist device.

PMID- 15235858
TI  - Epidural anesthesia for a patient with acute idiopathic pandysautonomia.

PMID- 15235859
TI  - Accidental admixing of compressed air to oxygen.

PMID- 15235860
TI  - Anesthesia and von Hippel-Lindau disease associated with pheochromocytoma.

PMID- 15235861
TI  - Pulmonary edema after anesthesia-related laryngospasm.

PMID- 15235862
TI  - Postanesthetic malignant hyperthermia with convulsions.

PMID- 15235863
TI  - A case of a massive ovarian tumor.

PMID- 15235864
TI  - Airway obstruction associated with induction of general anesthesia in a patient
      with mediastinal tumor.

PMID- 15235865
TI  - Basic mistakes seen in abstracts and reports written in English by Japanese
      anesthesiologists.

PMID- 15235866
TI  - Reg protein is a unique growth factor of gastric mucosal cells.
AB  - In 1984, Reg protein was shown to be stimulated during the regeneration of
      pancreatic islets. Since then, many Reg-related proteins have been identified in
      humans and other animals. These Reg-related proteins are classified into four
      subfamilies according to their amino-acid sequences, but they share a similar
      structure and physiological function. The role of Reg in gastric tissue was
      investigated, and Reg I was found to be expressed mainly in gastric fundic
      enterochromaffin-like (ECL) cells. Reg I production in ECL cells is stimulated by
      gastrin, as well as by the proinflammatory cytokine, cytokine-induced neutrophil
      chemoattractant (CINC)-2Beta. In patients with chronic hypergastrinemia, Reg
      production is stimulated, with the increased proliferation of gastric mucosal
      cells. Patients with Helicobacter pylori infection also showed increased Reg
      production in the gastric mucosa, partly via increased plasma gastrin
      concentration and partly via increased proinflammatory cytokine production. Thus,
      Reg protein induced by H. pylori infection may be partly responsible for the
      increased proliferation of gastric epithelial cells in H. pylori-infected
      patients. Reg protein is also produced in many gastric cancer cells, especially
      in poorly differentiated and advanced cancers. Reg protein stimulates the
      proliferation of several gastric cancer cell types, and gastric cancers with Reg
      protein expression tend to show a poorer clinical outcome. In summary, Reg
      protein may be a growth factor that regulates the proliferation and
      differentiation of normal and neoplastic gastric epithelial cells.

PMID- 15235867
TI  - 5-ASA and lycopene decrease the oxidative stress and inflammation induced by iron
      in rats with colitis.
AB  - BACKGROUND: Supplementation of 5-aminosalicylic acid (5-ASA) and of iron are
      among the principal therapies in patients with inflammatory bowel disease.
      Therapeutic iron, as well as heme iron from chronic mucosal bleeding, can
      increase iron-mediated oxidative stress in colitis. This study was designed to
      examine the influence of iron supplementation on histological expression and
      oxidative status relative to 5-ASA treatment and antioxidant treatment. METHODS:
      Colitis was induced using the iodoacetamide rat model, and rats were divided into
      different dietary groups of 6 rats each: 1, normal chow diet (control); 2, diet
      supplemented with iron; 3, iron supplementation and lycopene; 4, iron and Beta
      carotene; 5, 5-ASA; 6, 5-ASA and lycopene; 7, 5-ASA and iron; 8, 5-ASA, iron, and
      lycopene. The animals were killed after 3 days and the weight of the ulcerated
      area recorded. Mucosal specimens were histologically evaluated. Myeloperoxidase
      (MPO) was measured to evaluate inflammatory status (U/g). Malondialdehyde (MDA)
      was measured in colonic tissue ( micro mol/g) and superoxide dismutase (SOD) in
      erythrocytes to assess the degree of tissue oxidative stress. RESULTS:
      Significantly more severe colitis, including necrosis, ulceration, and
      hemorrhage, was seen in colonic biopsies of rats with colitis when iron was
      supplemented. This pathology was attenuated when iron was given in combination
      with 5-ASA and/or lycopene. There was no significant benefit from adding Beta
      carotene. CONCLUSIONS: Iron supplementation can amplify the inflammatory response
      and subsequent mucosal damage in a rat model of colitis. We suggest that the
      resultant oxidative stress generated by iron supplementation leads to the
      extension and propagation of crypt abscesses, either through direct membrane
      disruption by lipid peroxidation or through the generation of secondary toxic
      oxidants. Simultaneous treatment with 5-ASA and/or lycopene minimizes the
      potential hazard of iron. Therefore, we suggest giving iron supplementation with
      5-ASA or lycopene or both.

PMID- 15235868
TI  - Inflammation of the gastric remnant after gastrectomy: mucosal erythema is
      associated with bile reflux and inflammatory cellular infiltration is associated
      with Helicobacter pylori infection.
AB  - BACKGROUND: Controversy exists concerning the role of bile reflux and
      Helicobacter pylori ( H. pylori) infection in the development of inflammation of
      the gastric remnant after gastrectomy. This study was designed to investigate
      association of bile reflux and H. pylori infection or both with inflammatory
      changes in the gastric remnant. METHODS: A questionnaire on GI symptoms was
      returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the
      gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI
      endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of
      H. pylori infection and chronic, active inflammatory cellular infiltration in the
      biopsy specimens were examined microscopically with the updated Sydney system.
      RESULTS: No difference in the incidence of GI symptoms was observed among
      individual gastrectomy patients. Bile reflux was lower in patients who had
      undergone a gastrectomy with jejunal interposition, a pylorus-preserving
      gastrectomy, and a gastrectomy with Roux-Y anastomosis than those who had
      undergone a Billroth-II (B-II) anastomosis ( P < 0.05). Endoscopy showed positive
      correlation between mucosal erythema and bile reflux ( P < 0.001). No correlation
      was observed between the mucosal erythema and chronic and active inflammatory
      cellular infiltration. Infection of H. pylori correlated with chronic and active
      inflammatory cellular infiltration ( P < 0.001). Bile reflux did not correlate
      with the severity of chronic and active inflammatory cellular infiltration or H.
      pylori infection. CONCLUSIONS: Bile reflux into the gastric remnant was observed
      by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell
      infiltration in the gastric remnant after gastrectomy may be caused by bile
      reflux or H. pylori infection, respectively.

PMID- 15235869
TI  - Risk factors for vitamin D deficiency in patients with Crohn's disease.
AB  - BACKGROUND: Although the pathogenesis of osteopenia in Crohn's disease is not
      established, vitamin D deficiency is thought to be an important risk factor.
      However, little is known about the prevalence of vitamin D deficiency in patients
      with Crohn's disease in Japan. This study aimed to clarify the prevalence of
      vitamin D deficiency in patients with Crohn's disease in Japan and to examine the
      possible causes of the deficiency. METHODS: We investigated serum 25
      hydroxyvitamin D (25-OHD) levels, various laboratory parameters, and patient
      histories in 33 outpatients (25 men, 8 women; median age, 37 years; range, 26-57
      years) and 15 age- and sex-matched healthy controls (8 men, 7 women; median age,
      37 years; range, 24-57 years) and assessed risk factors for vitamin D deficiency.
      RESULTS: Although patients with Crohn's disease did not have significantly lower
      serum concentrations of 25-OHD than controls, 9 of 33 patients (27.3%) were
      considered vitamin D deficient (serum 25-OHD level </=10 ng/ml) compared with
      only 1 of 15 (6.7%) controls. Serum 25-OHD levels were significantly related to
      disease duration ( r = 0.46, P = 0.003), Crohn's Disease Activity Index (CDAI)
      score ( r = 0.44, P = 0.005), International Organization for the Study of
      Inflammatory Bowel Disease score ( r = 0.30, P < 0.05), and serum values of
      ferritin ( r = 0.34, P = 0.03), C-reactive protein ( r = 0.34, P = 0.03), total
      cholesterol ( r = 0.31, P = 0.04), and intact parathyroid hormone ( r = 0.23, P <
      0.05). A logistic regression analysis was performed to investigate the ability of
      variables to predict low or normal 25-OHD values. Results showed that disease
      duration ( P = 0.03) and CDAI score ( P = 0.04) could predict the occurrence of
      vitamin D deficiency ( r(2) = 0.472, P = 0.0004). CONCLUSIONS: Vitamin D
      deficiency exists in patients with Crohn's disease in Japan. 25-OHD levels should
      be assessed in patients who have had Crohn's disease for a long time (>15 years)
      and who have been in the active stage of the disease for long periods.

PMID- 15235870
TI  - Correlations between lymph node metastasis and depth of submucosal invasion in
      submucosal invasive colorectal carcinoma: a Japanese collaborative study.
AB  - BACKGROUND: Depth of submucosal invasion (SM depth) in submucosal invasive
      colorectal carcinoma (SICC) is considered an important predictive factor for
      lymph node metastasis. However, no nationwide reports have clarified the
      relationship between SM depth and rate of lymph node metastasis. Our aim was to
      investigate the correlations between lymph node metastasis and SM depth in SICC.
      METHODS: SM depth was measured for 865 SICCs that were surgically resected at six
      institutions throughout Japan. For pedunculated SICC, the level 2 line according
      to Haggitt's classification was used as baseline and the SM depth was measured
      from this baseline to the deepest portion in the submucosa. When the deepest
      portion of invasion was limited to above the baseline, the case was defined as a
      head invasion. For nonpedunculated SICC, when the muscularis mucosae could be
      identified, the muscularis mucosae was used as baseline and the vertical distance
      from this line to the deepest portion of invasion represented SM depth. When the
      muscularis mucosae could not be identified due to carcinomatous invasion, the
      superficial aspect of the SICC was used as baseline, and the vertical distance
      from this line to the deepest portion was determined. RESULTS: For pedunculated
      SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk
      invasion cases with SM depth <3000 micro m if lymphatic invasion was negative.
      For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth
      was <1000 micro m. CONCLUSIONS: These results clarified rates of lymph node
      metastasis in SICC according to SM depth, and may contribute to defining
      therapeutic strategies for SICC.

PMID- 15235871
TI  - Analysis of Ki-ras gene mutations within the same tumor using a single tumor
      crypt in colorectal carcinomas.
AB  - BACKGROUND: The point mutations occurring in codons 12 and 13 of the Ki- ras gene
      are useful genetic markers to identify intratumoral heterogeneity. A single tumor
      crypt, which consists of monoclonal cells, can be obtained using the crypt
      isolation method. Ki- ras gene mutations have been examined using the crypt
      isolation method to determine whether multiclonarity is present within the same
      tumor. METHODS: Ki- ras gene mutations were analyzed using a crypt isolation
      technique coupled with polymerase chain reaction and direct sequencing in 21
      sporadic colorectal carcinomas. The specimens were divided into two groups: a
      representative sample, which was composed of more than 50 tumor crypts, and a
      single tumor crypt sample. The latter consisted of 10 single tumor crypts, which
      were obtained from the same tumor separately. RESULTS: Ki- ras gene mutations
      were found in 11 of 21 representative samples and in 12 of 21 single tumor crypt
      samples. In the 11 samples with Ki- ras mutation, Ki- ras mutations were also
      found in most single tumor crypts. Among the 12 base substitutions found, G:C to
      A:T transitions were the most commonly observed. There were no differences
      between the two samples in the types of Ki- ras mutations found. One Ki- ras
      mutation that was not detected in the representative sample was observed in only
      a single tumor crypt. CONCLUSIONS: Most carcinomas appear to have a homogeneous
      composition that may result from the successful progression of one of the clones
      having a Ki- ras mutation. Additional mutations in the Ki- ras gene were rarely
      observed in colorectal carcinomas.

PMID- 15235872
TI  - Hepatocellular carcinoma in noncirrhotic young adult patients with chronic
      hepatitis B viral infection.
AB  - BACKGROUND: The aims of this study were to define the clinical characteristics of
      hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in young adult
      patients without cirrhosis and to evaluate the efficacy of interferon (IFN)
      therapy on HCC recurrence. METHODS: Of 187 patients with HBV-related HCC treated
      at our hospital, 4 had no liver cirrhosis and were less than 30 years of age (10,
      22, 23, and 26 years). RESULTS: At the time of diagnosis of HCC, all cases had
      antibody to hepatitis B e antigen (anti-HBe) and histological staging of
      nontumorous liver was F0 or F1, i.e., low-grade hepatitis. The mothers of all 4
      young adult patients with HCC had HBV-related liver disease. Three cases
      developed recurrence of HCC. In these patients, long-term intermittent IFN
      therapy after reresection of HCC resulted in long-term survival without
      recurrence for more than 3 years of follow-up. CONCLUSIONS: (1) Young adult
      patients with HCC are positive for anti-HBe, lack cirrhosis, and the route of
      infection seems to be mother-to-infant transmission. Transplacental transmission
      of HBV and HBV DNA integration into the cellular genomic DNA during fetal life is
      a possible explanation of HBV-related hepatocarcinogenesis in young adults; and
      (2) long-term IFN therapy seems to be useful for prevention of tumor recurrence
      after radical operation for HBV-related HCC.

PMID- 15235873
TI  - The harmful effect of exercise on reducing taurine concentration in the tissues
      of rats treated with CCl4 administration.
AB  - BACKGROUND: We have previously reported that oral taurine administration reduced
      the frequency of painful muscle cramps in patients with liver cirrhosis, and that
      skeletal muscle taurine concentration was significantly decreased after exercise.
      The aim of this study was to examine taurine concentration in various tissues of
      a liver damaged with fibrosis (LD) in a rat model before and after exercise.
      METHODS: Rats were divided into normal (NML) and LD groups. The LD group received
      CCl(4) injection for 10 weeks. Thereafter, both groups were divided into control
      (NML/CTL, LD/CTL) and exercise (NML/EX, LD/EX) groups, respectively. The rats in
      the EX groups were subjected to treadmill running. Plasma, liver, brain, heart,
      and skeletal muscle taurine concentration, as well as plasma and liver lipid
      peroxidase (LPO) concentration, were measured. RESULTS: The liver, brain, and
      skeletal muscle taurine concentration in the LD groups was significantly
      decreased compared to that in the respective NML groups. Furthermore, the taurine
      concentration in the heart and skeletal muscles in the LD/CTL group was
      significantly decreased post exercise. The respective plasma and liver LPO
      concentration in the LD groups was significantly increased compared to that in
      the corresponding NML group. Moreover, plasma LPO concentration in the LD/EX
      group was significantly higher than in the LD/CTL group. CONCLUSIONS: Tissue
      taurine concentration, particularly in skeletal muscle, was significantly
      decreased in the LD model rats induced by CCl(4) administration, and furthermore,
      the significantly decreased concentration, except for liver, was aggravated by
      exercise, even though at lower intensity.

PMID- 15235874
TI  - Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular
      carcinoma.
AB  - BACKGROUND: Silencing of the suppressor of cytokine signaling ( SOCS-1) by
      aberrant methylation at the CpG island in the coding region gene has been
      reported in hepatocellular carcinoma (HCC). However, principally, it is
      methylation in the 5'-noncoding region but not that in the coding region which
      determines the regulation of gene expression. METHODS: Methylation-specific PCR
      was performed for the analysis of methylation status both in the 5'-noncoding
      region and the CpG island of SOCS-1 from 22 HCC tissue samples with adjacent non
      HCC tissue samples and from two cell lines. RESULTS: Using primers in the CpG
      island, 9 of 22 HCC samples exhibited aberrant methylation of SOCS-1, while only
      1 of 22 adjacent non-HCC samples did so. The unmethylation pattern was detected
      in 1 of 22 HCC and in 5 of 22 non-HCC samples. Thus, aberrant methylation of SOCS
      1 was significantly associated with HCC ( P = 0.0076 by Fisher's exact test).
      Using primers in the 5'-noncoding region, aberrant methylation was observed in 12
      of 22 HCC and in 2 non-HCC samples. The unmethylated pattern was observed in 5 of
      22 HCC and in 10 of 22 non-HCC samples ( P = 0.0042). There was no significant
      correlation between the methylation status of SOCS-1 and clinicopathological
      findings, such as the presence or absence of cirrhosis or the histological grade
      of HCC. CONCLUSIONS: Aberrant methylation of the SOCS-1 had a significant
      correlation with HCC. The rate of aberrant methylation was similar in the 5'
      noncoding region and in the CpG island. Aberrant methylation of SOCS-1 may be
      associated with hepatocarcinogenesis, although further studies are necessary.

PMID- 15235876
TI  - Polypoid arteriovenous malformation of colon mimicking inflammatory fibroid
      polyp.
AB  - Arteriovenous malformation is a well-known cause of lower gastrointestinal
      bleeding in the elderly and usually appears as flat or elevated bright red
      lesions endoscopically. Here we present a 59-year-old woman with a large
      fungating polypoid mass in the transverse colon. Histologically, the larger
      vessels were located mainly in the submucosa, and smaller vessels were also
      observed within the mucosa. Verhoeff's elastic stain showed internal and external
      elastic lamina in the malformed vessels. We report an extremely rare case of a
      large, pedunculated, polypoid arterioveneous malformation with the first
      description of our complete pathological findings.

PMID- 15235875
TI  - A significant reduction in serum alanine aminotransferase levels after 3-month
      iron reduction therapy for chronic hepatitis C: a multicenter, prospective,
      randomized, controlled trial in Japan.
AB  - BACKGROUND: Increasing evidence indicates that iron cytotoxicity plays an
      important role in the pathogenesis of chronic hepatitis C (CHC). However, the
      biochemical effects of iron reduction therapy on CHC remain to be confirmed in a
      controlled study. This study aimed to test whether iron removal by repeated
      phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with
      CHC. METHODS: Patients were randomly assigned to an iron reduction therapy or
      control group. The patients in the treatment group received 3-month iron
      reduction therapy by biweekly phlebotomy, while the patients in the control group
      were followed up for 3 months with regular blood tests alone. RESULTS: Thirty
      three patients completed the 3-month treatment, while 29 patients received the
      complete follow-up. The serum ALT levels were reduced from 118 +/- 79 to 73 +/-
      39 IU/L in the treatment group, but did not change in the control group (106 +/-
      45 versus 107 +/- 48 IU/L). Posttreatment enzyme activity was decreased
      significantly from the baseline. Furthermore, it was significantly lower than the
      3-month control level. Although 5 patients withdrew from the study, none was
      affected by any side effects of repeated phlebotomy that required them to
      discontinue the treatment. CONCLUSIONS: This short-term controlled trial
      demonstrated the biochemical efficacy and safety of iron reduction therapy for
      patients with CHC.

PMID- 15235877
TI  - Melanocytic differentiation in a solid pseudopapillary tumor of the pancreas.
AB  - Solid pseudopapillary tumor of the pancreas (SPT) is an uncommon neoplasm of low
      malignant potential, generally occurring in young women. The tumor is indolent,
      usually with long survival, even in the presence of extension into adjacent
      organs and metastases. Pathological features include solid, cellular, and cystic
      regions and degenerative pseudopapillae formation. Despite its distinctive
      morphology and cytological features, the cell lineage of this entity is unclear.
      Here we report a case of solid pseudopapillary tumor in a 48-year-old man with 10
      year follow-up in which melanin pigment was found within the tumor cells. The
      tumor cells stained positive not only for melanocytic markers including S-100,
      HMB-45, and Fontana, but also other well-established markers for this kind of
      neoplasm such as alpha-antitrypsin (Alpha-AT), anti-alpha-chymotrypsin (AACT),
      NSE, CD10, cyclin D1, and beta-catenin. Electron microscopy confirmed the
      formation of premelanosomes and melanosome granules in the tumor cells. To our
      knowledge, this is the first report in which melanosomes were produced by SPT.
      Because melanocytes are derived from neurocrest, we hypothesize that the
      histogenesis of SPT is of neurocrest origin. This phenomenon may also be
      explained by ongoing research in which it has been shown that Wnt signaling/beta
      catenin intranuclear localization promotes pigment cell formation by medial crest
      cells in embryos.

PMID- 15235878
TI  - Intraductal growth of a nonfunctioning endocrine tumor of the pancreas.
AB  - Intraductal growth of nonfunctioning endocrine tumors of the pancreas may be very
      rare, and our survey of literature shows only two cases have been described. We
      report a case of a 43-year-old man with a nonfunctioning endocrine tumor of the
      pancreas that uniquely grew within the lumen of the main pancreatic duct (MPD)
      without ductal involvement and completely obstructed the MPD. Endoscopic
      ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)
      were very helpful to delineate the intraductal growth of the tumor and to
      determine the resection line of the pancreas. A nonfunctioning pancreatic
      endocrine tumor is important to consider on differential diagnoses when complete
      obstruction of the MPD is demonstrated on ERCP. It is speculated that the tumor
      originated from precursor cells of the pancreatic duct or islet cells adjacent to
      the MPD and slowly proliferated within the lumen of the MPD.

PMID- 15235879
TI  - Enterovesical fistula complication in B-cell-type lymphoma of the small
      intestine.

PMID- 15235880
TI  - Bracket fungi-induced enteritis.

PMID- 15235881
TI  - Acute pancreatitis complicating ulcerative colitis under administration of
      corticosteroid in surgical cases.

PMID- 15235882
TI  - A case of adrenal metastasis from rectal carcinoma without lung metastasis:
      evaluation for alteration of loss of heterozygosity and immunohistochemical
      expression.

PMID- 15235883
TI  - In which step does the K-ras mutation occur in colorectal carcinogenesis?

PMID- 15235884
TI  - Suppressor of cytokine signaling 1, a newly proposed tumor suppressor gene
      associated with hepatocellular carcinoma.

PMID- 15235885
TI  - Phlebotomy: a promising treatment for chronic hepatitis C.

PMID- 15235886
TI  - Feasibility of hanging maneuvers in orthotopic liver transplantation with
      inferior vena cava preservation and in liver surgery.
AB  - BACKGROUND/PURPOSE: The aim of this work was to study the feasibility and
      complication rates of liver hanging maneuvers: the Belghiti liver hanging
      maneuver (BLHM) in liver resection and the modified liver hanging maneuver (MLHM)
      in orthotopic liver transplantation (OLT) with inferior vena cava (IVC)
      preservation. METHODS: From January 2001 to August 2003, BLHM was planned in 26
      consecutive right hepatectomies and MLHM in 28 consecutive OLTs with IVC
      preservation. RESULTS: BLHM was performed in 24/26 patients (92%). In the 2
      remaining patients, chronic biliary infection (n = 1) and intraparenchymal
      hemorrhagic hepatocellular carcinoma (n = 1) did not allow BLHM to be achieved.
      Bleeding during the BLHM procedure occurred in 1 patient (4%), with no need for
      interruption. MLHM was performed in all 28 patients, and in none of them was
      bleeding observed during the maneuver. CONCLUSIONS: BLHM and MLHM are important
      technical refinements with several advantages. Feasibility rates were 92% and
      100%, respectively. Bleeding risk remained low (4%) for BLHM and was 0% for MLHM.
      The rate of BLHM failure suggests that the feasibility rate may be higher in
      normal liver parenchyma.

PMID- 15235887
TI  - A new diagnostic approach to pancreatic pseudocyst fine-needle puncture: three
      dimensional sonography.
AB  - BACKGROUND/PURPOSE: We evaluated the usefulness of three-dimensional (3D)
      sonography in percutaneous fine-needle pancreatic pseudocyst puncture. METHODS:
      We examined 52 patients diagnosed as having pancreatic pseudocysts on the basis
      of clinical symptoms and two-dimensional (2D) ultrasonography findings. The
      decision to qualify certain patients for percutaneous fine-needle aspiration
      guided by ultrasonography was made on the basis of 2D and 3D scan results. Spiral
      computed tomography was done when the presence of connections between pseudocyst
      and pancreatic duct was suspected. In these cases diagnosis was confirmed in
      operative procedures. 3D sonography was used to monitor the tip of the needle
      making its way to the pancreatic pseudocyst and later inside the fluid
      collection. RESULTS: Pancreatic pseudocysts were diagnosed in all 52 cases; 48
      patients underwent percutaneous fine-needle biopsies. CONCLUSIONS: 3D
      presentation can better visualize irregular shapes, local thickenings, and
      calcification of pseudocyst walls than classical 2D ultrasound scans. The use of
      subtraction in 3D scans of blood vessels increases the safety in performing
      biopsies. We have shown that 3D sonography collects extremely useful information
      about the status of the pseudocyst structure, and it should become a
      complementary method to classical ultrasonography. This technique when used on a
      routine basis should help us change the inclusion criteria for guided biopsies.

PMID- 15235888
TI  - Expression of vascular endothelial growth factor and receptor flk-1 in colon
      cancer liver metastases.
AB  - BACKGROUND/PURPOSE: This study investigated vascular endothelial growth factor
      (VEGF) and flk-1 expression in hepatic metastases from colon carcinoma, and their
      associations with tumor angiogenesis, proliferation, and apoptosis. METHODS:
      Immunohistochemical studies were performed for VEGF/flk-1, Ki-67, p53, and bcl-2
      expression, and microvessel density (MVD) in surgical specimens from 35 patients
      who underwent hepatectomy for colon cancer liver metastases between 1986 and
      2001. RESULTS: VEGF and flk-1 were expressed mainly in the cytoplasm of tumor
      cells. High VEGF expression was associated with high flk-1 expression (P =
      0.043). MVDs of less than 15 and 15 or more were found in 5 (14.3%) and 30
      (85.7%) of 35 hepatic metastases, respectively. A Ki-67 index (KI) of 50% or more
      was detected in 33/35 (94.3%) of tumors, and 23 of these (65.7%) showed a KI of
      85% or more. A KI of less than 50% was present in 2/35 (5.7%) of tumors. The
      expression of VEGF/flk-1 was related to elevated MVD (P < or = 0.026). VEGF was
      also associated with an increased KI (P = 0.025). Mutant p53 and bcl-2
      expressions were detected in 26/35 (74.3%) and 17/35 (48.6%) of liver metastases,
      respectively. Mutant p53 was not related to VEGF/flk-1 expression, but bcl-2 was
      highly associated with flk-1 (P = 0.007). The incidences of high flk-1 expression
      and a KI of 85% or more were significantly higher in tumors which were both p53-
      and bcl-2-positive (93.3% and 73.3%) than in tumors which were negative for both
      (42.9% and 14.3%; P < or = 0.021). CONCLUSIONS: The VEGF-flk-1 system takes part
      in tumor angiogenesis, proliferation, and apoptosis in colon liver metastases.
      The bcl-2 pathway may upregulate VEGF activity via the flk-1 receptor. These
      findings are preliminary, requiring a larger sampling in order to elucidate the
      role of VEGF/flk-1 in metastatic colon cancer.

PMID- 15235889
TI  - Usefulness of both operative cholangiography and conversion to decrease major
      bile duct injuries during laparoscopic cholecystectomy.
AB  - BACKGROUND/PURPOSE: We evaluated the role of operative cholangiography and of
      conversion to decrease major bile duct injuries. METHODS: We report 1074 patients
      who underwent laparoscopic cholecystectomy, out of a total of 1195 patients who
      underwent laparoscopy, over an 8-year period. The planned laparoscopic operative
      procedure in all the patients was the standard four-port technique with the
      operator on the left side of the patient. Operative cholangiography was performed
      with Olsen's pliers. RESULTS: We performed 993 (83%) operative cholangiographies;
      121 (10.1%) patients were converted from laparoscopic to open cholecystectomy.
      Despite a prolonged time of dissection, 54 (4.5%) patients were converted because
      of unclear anatomy of Calot's triangle. One hundred and ninety patients suffered
      acute cholecystitis and, of those, 52 (27.3% of 190 patients) were converted.
      Fifteen patients showed intraoperative biliary duct stones and they were
      converted. Seven (0.58%) bile duct injuries (one stricture and six fistulas) are
      reported. CONCLUSIONS: The low number of major bile duct injuries reported in our
      study showed the value of operative cholangiography during laparoscopic
      cholecystectomy. Moreover, another important factor found to reduce major bile
      duct injuries was conversion when, despite accurate dissection, the anatomy of
      Calot's triangle remained unclear.

PMID- 15235890
TI  - Short-term effects of external and internal biliary drainage on liver and
      cellular immunity in experimental obstructive jaundice.
AB  - BACKGROUND/PURPOSE: The effects of preoperative biliary drainage for obstructive
      jaundiced patients are controversial. Although experimental studies have proven
      the benefit of internal biliary drainage (ID) over external biliary drainage
      (ED), ID has several clinical problems, such as clogging or tube replacement. The
      aim of this study was to determine whether there were any differences in T-cell
      function, liver function, and histology, between rats in ID and ED groups in
      short-term experiments. METHODS: Following bile duct ligation (BDL) for 14 days,
      rats in the ED and ID groups had 7 days of ED and 7 days of ID, respectively.
      Normal rats were used as negative controls (control group). For positive
      controls, we used a group with BDL and no drainage (BDL group). Serum bilirubin,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
      phosphatase (ALP) were measured, splenic T-cell proliferation was assayed to
      check cellular immunity, and liver histology was examined. RESULTS: Recovery of
      bilirubin and ALT was similar in the ED and ID groups. Recovery of AST was worse
      in the ID group than in the ED group, but the difference was not statistically
      significant. Levels of ALP in the BDL and ID groups were significantly higher
      than those in the control and ED groups. Rats in the BDL group showed a
      significant decrease in T-cell function compared to the control group. The ED
      group showed better recovery of T-cell function than the ID group in the 7 days
      after relief of obstructive jaundice. The livers in the ID group demonstrated
      histologically moderate interface hepatitis with periportal inflammation and
      lymphocyte infiltration, which strongly suggested incomplete tube obstruction,
      but those in the ED group showed minimal change. CONCLUSIONS: ED is superior to
      ID concerning the recovery of cellular immunity and liver inflammation in the
      short-term after relief from biliary obstruction in this model. As the patency of
      the tube is well maintained in ED compared to ID, patency of the tube is
      essential to obtain good recovery of cellular immunity, irrespective of the
      drainage method.

PMID- 15235891
TI  - D-Allose has a strong suppressive effect against ischemia/reperfusion injury: a
      comparative study with allopurinol and superoxide dismutase.
AB  - BACKGROUND/PURPOSE: D-Allose, a rare sugar, is one of the potent inhibitors of
      ischemia/reperfusion injury of the rat liver. To investigate the potency of this
      powerful agent we examined its effect against ischemia/reperfusion injury and
      compared it to that of allopurinol and superoxide dismutase. METHODS: Male Lewis
      rats were given water ad libitum preoperatively for 12 h and anesthetized by
      isoflurane inhalation anesthesia. Drugs were administered through a polyethylene
      catheter inserted into the portal vein for 2 h (D-allose), 10 min (allopurinol),
      or 5 min (superoxide dismutase) before ischemia, and the livers were then
      subjected to 70% ischemia, induced by crossclamping the vessels to the lateral
      and median lobes of the liver for 90 min. Rats were divided into four groups:
      group 1, pretreated with vehicle (normal saline); group 2, treated with D-allose;
      group 3, treated with allopurinol; and group 4, treated with superoxide
      dismutase. The effects of the drugs were evaluated by liver hemodynamics,
      neutrophil count, myeloperoxidase, liver enzymes, and histological studies.
      RESULTS: D-Allose improved liver hemodynamics (P < 0.001) and postischemic animal
      survival (P < 0.05) significantly compared with the control group and
      nonsignificantly compared with the allopurinol and superoxide dismutase groups.
      Myeloperoxidase activity in the postischemic liver tissue was decreased
      significantly (P < 0.05) by D-allose compared with all other treatment and
      control groups. Neutrophil count was also significantly (P < 0.05) decreased in
      the D-allose group compared with than that in the control group, as well as the
      superoxide dismutase group. Only D-allose produced a statistically significant
      decrease in the level of liver enzymes, compared with levels in the control
      group. CONCLUSIONS: The moderately protective effect of D-allose, which caused no
      clinical side effects, is encouraging. D-Allose had the best protective effect
      against neutrophil-related postischemic injury of the liver tissue, followed by
      allopurinol and superoxide dismutase. However, a more extensive study is needed
      to ensure the effects as well as the mechanisms of the effect of this rare sugar.

PMID- 15235892
TI  - Cholelithoptysis: an unusual delayed complication of laparoscopic
      cholecystectomy.
AB  - We report the case of a 54-year old woman who presented with a persistent right
      lower lobe pneumonia followed by cholelithoptysis, 11 months after a laparoscopic
      cholecystectomy. It is postulated that this was a result of the formation of a
      subphrenic abscess secondary to intraoperative spillage of gallstones. It is
      concluded that spillage of gallstones at laparoscopic cholecystectomy is not as
      benign as previously thought and that efforts to prevent spillage should include
      scrupulous operative technique, especially in the presence of gallbladder
      inflammation, and especial care when removing the gallbladder from the abdominal
      cavity.

PMID- 15235893
TI  - A resected case of a small hepatocellular carcinoma developing within the bile
      duct.
AB  - We experienced a resected case of a small hepatocellular carcinoma, which
      required differential diagnosis from intrahepatic cholangiocellular carcinoma.
      The patient was a 76-year-old man. While his course had been being observed
      because of hepatitis C antibody-positive liver cirrhosis, ultrasonographic
      examination of the abdomen revealed dilation of biliary branches in the anterior
      segment of the liver and a hyperechoic mass 10 mm in diameter at the origin of
      the branch. A dynamic computed tomography scan showed a high-density tumor in the
      early phase. After embolization of the right branch of the portal vein, resection
      of the right lobe of the liver and the extrahepatic bile duct was performed. A
      resected specimen showed a white-colored mass 8 mm in diameter at the origin of
      the anterior segmental biliary branch. In the pathological findings, the
      diagnosis was a poorly differentiated hepatocellular carcinoma with strong
      nuclear atypia; the tumor filled the bile duct, forming a trabecular structure.
      The immunohistological stains of the tumor were positive for cytokeratin (CK) 8,
      CK18, and HepParl and negative for alpha-fetoprotein, carcinoembryonic antigen,
      CA19-9, CK7, CK19, and CK20. There was atypia in the biliary lining epithelium
      adjacent to the tumor, and the hepatocellular carcinoma may have developed from
      the biliary epithelium.

PMID- 15235894
TI  - Axillary lymph node metastasis following resection of abdominal wall laparoscopic
      port site recurrence of gallbladder cancer.
AB  - Abdominal wall port site recurrence of gallbladder cancer is well described in
      the literature in patients that have undergone laparoscopic cholecystectomy with
      the incidental finding of a gallbladder cancer. The etiology and consequences of
      this type of metastatic recurrence are unclear. This report describes two cases
      with the unique sequelae of the interval development of nodal metastases to the
      axillary lymph nodes following resection of an abdominal wall laparoscopic port
      site recurrence of gallbladder cancer. The first case involves a patient who
      developed an isolated left axillary lymph node metastasis approximately 10 months
      after undergoing resection of a left-sided abdominal wall port site recurrence
      for a T2 gallbladder cancer. The original tumor had been found at laparoscopic
      cholecystectomy and definitively treated surgically approximately 3 years
      earlier. The second case involves a patient who developed isolated nodal
      metastases to the right axillary lymph nodes approximately 4 months after
      undergoing resection of right-sided abdominal wall port site recurrence, segment
      4/5 hepatic resection, and portal lymphadenectomy for a T2 gallbladder cancer.
      This tumor had originally been found at laparoscopic cholecystectomy
      approximately 1 year earlier. These unique sequelae of the interval development
      of nodal metastases to the axillary lymph nodes demonstrated in both cases has
      not been previously reported.

PMID- 15235895
TI  - Localization of islet-cell hyperplasia: value of pre- and intraoperative arterial
      stimulation and venous sampling.
AB  - Arterial stimulation and venous sampling was effective in the localization of
      Beta-cell hyperplasia of the pancreas in the islets of Langerhans in an 84-year
      old woman. The patient presented with repeated episodes of unconsciousness and
      hypoglycemia. She was first suspected of having insulinoma, but diagnostic
      imaging failed to reveal any tumors. Arterial stimulation and venous sampling
      (ASVS) and percutaneous transhepatic portal venous sampling (PTPS) were performed
      to localize the tumor. By ASVS, increases in immuno reactive insulin (IRI) were
      noted in renal vein blood samples (because a splenorenal shunt was present) after
      splenic arterial stimulation and venous sampling, and PTPS revealed a stepup in
      IRI from splenic venous blood samples. Preoperative diagnosis suggested Beta-cell
      hyperplasia in the pancreas tail. Intraoperative ultrasound failed to find a
      tumor. Intraoperative ASVS showed the site of increase IRI as the pancreas tail,
      so distal pancreatectomy and splenectomy were performed. However, hypoglycemia
      was observed constantly after this operation. Relaparotomy, causing additional
      resection, was conducted to confirm the precise location and to remove the
      residual Beta-cell hyperplasia of the pancreas. At the second resection, the
      existing part of Beta-cell hyperplasia was confirmed through intraoperative ASVS,
      and additional resection of the pancreas body and neck was performed. At this
      time, complete removal of the residual Beta-cell hyperplasia was confirmed
      through ASVS. The hypoglycemia and impaired consciousness disappeared after the
      operation, and the patient's blood sugar level was maintained at a normal level.
      Pathological findings revealed islets of Langerhans hyperplasia extending to 1 cm
      in the pancreas tail region. We conclude that pre- and intraoperative ASVS is a
      useful test for Beta-cell hyperplasia, which is difficult to diagnose through
      ordinary imaging techniques.

PMID- 15235896
TI  - Operated hepatocellular carcinoma in two HIV- and HCV-positive hemophilic
      patients.
AB  - Some hemophilic patients in Japan suffer from infections with both human
      immunodeficiency virus (HIV) and hepatitis virus because they received
      contaminated nonheated blood products. Coinfection with HIV appears to accelerate
      the course of chronic hepatitis. Although powerful antiviral therapy was
      introduced as HIV treatment and the prognosis of HIV patients was dramatically
      improved, the risk of rapid progression of hepatitis and carcinogenesis remains
      for the patients. Recently, we performed surgery for hepatocellular carcinoma
      (HCC) in two hemophilic patients with HIV and hepatitis C virus (HCV)
      coinfection. Case 1 was a 52-years-old man who suffered from liver cirrhosis,
      hypersplenism, and hyperammonemia due to portosystemic shunt. A recent abdominal
      computed tomography (CT) scan had revealed a low-density area in segment VI of
      the liver. Splenectomy and partial resection of the liver were performed. Case 2
      was a 66-year-old man who had been diagnosed with chronic hepatitis at age 50,
      and HIV infection at age 52 years. When his serum alpha-fetoprotein level was
      increased, CT scan of the liver revealed a mass in segment VIII. Subsegmentectmy
      of the liver was performed. Although the CD4 value in each patient was lower than
      200 micro l, the operations were safely carried out and no major complication
      occurred. Because the chance of encountering HCC patients infected with HIV and
      HCV is increasing in Japan, we should consider the perioperative care of these
      patients, as well as the protection of medical workers against HIV infection.

PMID- 15235897
TI  - Live donor liver transplantation: staging hepatectomy in a Jehovah's Witness
      recipient.
AB  - Orthotopic liver transplantation (OLT) is usually associated with significant
      blood loss and frequently requires the usage of blood products. OLT has been
      offered sparingly in Jehovah's Witness (JW) patients because of their refusal to
      accept blood products for religious reasons. Several innovations have made
      surgery safer in these patients. These include the pre-operative use of
      erythropoietin to increase red cell mass, the use of intraoperative cell salvage
      and acute normovolemic hemodilution, and judicious postoperative blood testing.
      Thoughtful perioperative decision-making and careful surgical techniques remain
      the cornerstone to a successful outcome. We report our experience in a two-stage
      hepatectomy done for a JW patient who underwent live donor liver transplant from
      his mother, also a JW, without blood transfusion. The recipient had an unusually
      enlarged left lateral segment of the liver which was densely adherent to the
      spleen. Removing these adhesions in the presence of significant portal
      hypertension would have resulted in considerable blood loss. This was
      successfully avoided by leaving this portion of the liver attached to the spleen
      while proceeding with the hepatectomy. The right lobe of the liver from the donor
      was then implanted uneventfully. Two weeks later the remaining segment of the
      recipient liver was removed without incident. The two-stage procedure was life
      saving in this JW patient.

PMID- 15235898
TI  - Hepatocellular carcinoma associated with autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a disorder of unknown etiology, which often
      progresses to cirrhosis and carries a high mortality, even though its treatment
      with corticosteroids has become common. Hepatocellular carcinoma (HCC) has been
      reported as a rare complication of AIH. We describe herein a patient with HCC
      associated with AIH, in whom microwave coagulation therapy provided a means of
      definitive management, and we also review the literature. Male sex and
      longstanding cirrhosis seem to be the risk factors for hepatocarcinogenesis in
      AIH. The prognosis of this disease is extremely poor because of the low
      resectability caused by poor hepatic reserve. It is important to pay attention to
      hepatic disorders and the possible development of HCC at the time of diagnosis of
      AIH. Surgeons should select suitable treatment, without undue surgical stress,
      whenever the diagnosis of HCC has been established. Microwave coagulation therapy
      is a preferred option for the treatment of high-risk patients with poor hepatic
      reserve or unresectable multiple HCCs.

PMID- 15235899
TI  - LigaSure use in pancreatic surgery in patients with portal hypertension.

PMID- 15235900
TI  - Prognostic significance of wound infections following major head and neck cancer
      surgery: an open non-comparative prospective study.
AB  - OBJECTIVE: We evaluated the incidence, risk factors and consequences of wound
      infection (WI) following major head and neck cancer surgery in an open non
      comparative study. PATIENTS AND METHODS: The study group, comprising 95 patients
      who underwent clean-contaminated procedures with opening of the upper
      aerodigestive tract for biopsy-proven squamous cell cancer, were studied over a 1
      year period. Antibiotic prophylaxis was amoxicillin and clavulanic acid. More
      than 20 variables were prospectively recorded for each patient. The mean follow
      up was 30 months. MAIN RESULTS: The overall WI rate was 50.5% (48/95). Most
      pathogens isolated from samples were gram-negative rods. In univariate analysis,
      we found three risk factors for WI: alcohol consumption (P = 0.07), a
      hypopharyngeal location (P = 0.02) and laryngectomy stoma (P = 0.01). WI were
      associated with postoperative fever (P = l.5 x 10(-11)), postoperative antibiotic
      therapy (P = 1.5 x 10(-5)) and postoperative death (P = 0.043). Patients without
      WI had a median postoperative hospital stay of 15 days compared with 29 days for
      those with WI (P < 0.001). Healing of WI was achieved after a median time of 48
      days. WI delayed postoperative radiation therapy in 21 out of 33 evaluable
      patients. But overall survival, and local and metastatic failures were similar
      with and without WI. CONCLUSIONS: WI are associated with a heavy postoperative
      morbidity, but have no prognostic impact on cancer control.

PMID- 15235901
TI  - A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in
      chemotherapy-treated patients at high risk of developing febrile neutropenia.
AB  - BACKGROUND: Febrile neutropenia (FN) remains a major dose-limiting complication
      among patients treated with chemotherapy. Haematopoietic colony stimulating
      factors (G-CSF and GM-CSF) made possible a significant improvement in the
      management of FN, both in the therapeutic and in the prophylactic approach. The
      use of antibiotic prophylaxis also permits a definite reduction of severe
      infections during neutropenia. Nevertheless, the possible role of these two
      interventions for secondary prevention of FN is still unclear. PATIENTS AND
      METHODS: We conducted a prospective randomised trial by comparing the efficacy of
      granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with
      oral antibiotics in the secondary prevention of FN. We included in our study
      those patients who, after an episode of FN, continued to be treated with the same
      chemotherapy without reduction of dose intensity. They were randomised into two
      groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the
      second was treated with an association of G-CSF and amoxicillin/clavulanate plus
      ciprofloxacin (group G/ACC). RESULTS: Forty-eight patients were randomised (group
      G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients
      receiving G-CSF and only one episode in the combined therapy group (p=1). With
      regard to the side effects, there was no significant difference in the two
      groups. CONCLUSION: The use of G-CSF for the secondary prevention of FN is
      extremely effective and allows the maintenance of chemotherapy dose intensity.
      Our study showed that the addition of antibiotics does not seem to be required.

PMID- 15235902
TI  - Cost analysis of secondary prophylaxis with oral clodronate versus pamidronate in
      metastatic breast cancer patients.
AB  - OBJECTIVE: We compared the direct medical costs of secondary prophylaxis with
      bisphosphonates (BPs) in bone metastases (BMs) of breast cancer (BCa) from a
      payer perspective. PATIENTS AND METHODS: This study adopted an incidence-based
      chart review of consecutive BCa patients with BMs who received prophylactic
      treatment with orally administered (po) clodronate (CLODpo group), or
      intravenously administered (iv) pamidronate (PAM group) in 1997 at two large
      oncology centers in Toronto, Ontario. We evaluated the difference in costs of
      management of patients among the CLODpo and PAM groups using an intent-to-treat
      analysis from diagnosis of BMs to death, or last follow-up. The results are
      presented as observed mean and average lifetime (including terminal care) costs
      per patient. RESULTS: The observed mean costs in the PAM and CLODpo groups were
      49,472 dollars and 50,307 dollars (2002 Canadian dollars), respectively. The
      difference in costs between the CLODpo (n=34) and PAM (n=18) groups was not
      significant (P=0.64), and remained robust after sensitivity analyses. The
      corresponding average lifetime costs were 65,677 dollars in the CLODpo group and
      61,254 dollars in the PAM group. Inpatient and terminal care were the major cost
      drivers, comprising 45% and 25% of overall costs. Of all hospitalizations, 46%
      were associated with complications from BMs. CONCLUSIONS: Our analysis, which was
      based on a convenience sample, failed to reveal a statistically significant
      difference in the observed mean costs between groups of patients who initiated
      treatment with po clodronate versus iv pamidronate. The cost estimates from this
      study can be used for future corroborative economic analyses.

PMID- 15235903
TI  - Chytridiomycosis impacts predator-prey interactions in larval amphibian
      communities.
AB  - Despite ecologists increasingly recognizing pathogens as playing significant
      roles in community dynamics, few experimental studies have quantified patterns of
      disease impacts on natural systems. Amphibians are experiencing population
      declines, and a fungal pathogen ( Batrachochytrium dendrobatidis;
      Chytridiomycota) is a suspected causal agent in many declines. We studied the
      effects of a pathogenic fungus on community interactions between the gray
      treefrog, Hyla chrysoscelis, and eastern newts, Notophthalmus viridescens. Recent
      studies have characterized chytridiomycosis as an emerging infectious disease,
      whose suspected rapid range expansion and widespread occurrence pose a
      significant risk for amphibian populations worldwide. We reared larvae in outdoor
      polyethylene experimental tanks and tested the effects of initial larval density,
      predator presence, and fungal exposure on Hyla recruitment and predator-prey
      interactions between Hyla and Notophthalmus. Newts reduced treefrog survival, and
      high intraspecific density decreased metamorphic body mass independent of B.
      dendrobatidis. The presence of fungi reduced treefrog body mass at metamorphosis
      by 34%, but had no significant main effect on survival or larval period length.
      B. dendrobatidis differentially affected larval development in the presence of
      predators; Hyla developed slower when reared with the pathogen, but only when
      newts were present. This significant predator-by-pathogen interaction suggests
      that the impact of chytridiomycosis on larval amphibians may be exacerbated in
      complex communities. Our data suggest that B. dendrobatidis effects on host life
      history may be complex and indirect. Direct measurements of the community-level
      effects of pathogens offer an important opportunity to understand a significant
      threat to global biodiversity-declining amphibian populations.

PMID- 15235904
TI  - Qualitative and quantitative analysis of the effect of splicing mutations in
      propionic acidemia underlying non-severe phenotypes.
AB  - In this work we analyze splicing mutations identified in propionic acidemia
      patients to clarify their functional effects and their involvement in the disease
      phenotype. Two mutations in the PCCA gene detected in homozygous patients and
      involving consensus splice sequences (IVS21+3del4 and IVS22-2A>G) were shown to
      produce some normal splicing in patients' cells, at very low levels, which were
      quantitated by real-time PCR methods, and which presumably are sufficient to
      moderate the phenotype. We have also analysed the effect of mutations c.653A>G
      and IVS10-11del6 in the PCCB gene present in heterozygous patients with mild
      phenotype. The c.653A>G mutation is located in the last codon of exon 6 and
      interferes with the correct spliceosomal assembly activating a cryptic splice
      site within exon 6, which leads to an in-frame six-nucleotide deletion (delV217
      K218). Minigene analysis and sequence-specific hybridization probes using real
      time PCR methods showed that no normally spliced transcript is detectable in the
      patients' fibroblasts. The IVS10-11del6 mutation shortens the polypyrimidine
      tract of the 3'-splice site of exon 11, resulting in exon skipping. Some normal
      transcript is detectable by allele-specific hybridization probes. These analyses
      suggest that, in some cases, the regulation of gene splicing can potentially play
      an important role in human disease influencing phenotypic parameters.

PMID- 15235906
TI  - Gene expression patterns as marker for 5-year postoperative prognosis of primary
      breast cancers.
AB  - PURPOSE: To establish the novel prognostic markers for breast cancer, gene
      expression profile was examined genome-wide. METHODS: We used cDNA microarray
      consisting of 18,432 human genes to compare genome-wide expression profiles of
      eight primary breast cancers, four from patients who died of breast cancer within
      5 years after surgery (5D group) and four who survived disease-free for more than
      5 years (5S group). RESULTS: We identified 21 genes whose expression was greater
      in tumors from the 5D group than in 5S tumors, and 23 with higher expression in
      the 5S group than in the 5D group. We established a Prognostic Index (PI) for
      prediction of postoperative prognosis, based on the aberrant expression profiles
      of ten of those genes. Among 20 additional cases chosen blindly, ten presented
      with high prognostic scores (>7, good) according to the PI; the remaining ten
      cases revealed scores <7 (poor). The PI predicted the actual 5-year clinical
      outcomes of these 20 cases with 100% accuracy. CONCLUSION: Our PI system is
      reliable in clinical settings for predicting postoperative risk for breast
      cancer. The extensive list of genes provides valuable information about
      progression of breast cancer and suggests potential target molecules for treating
      this disease.

PMID- 15235907
TI  - Estimate of size and total number of neurons in superior cervical ganglion of
      rat, capybara and horse.
AB  - The superior (cranial) cervical ganglion was investigated by light microscopy in
      adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were
      vascularly perfused, embedded in resin and cut into semi-thin sections. An
      unbiased stereological procedure (disector method) was used to estimate ganglion
      neuron size, total number of ganglion neurons, neuronal density. The volume of
      the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The
      total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the
      number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats,
      capybaras and horses, respectively. The average neuronal size (area of the
      largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the
      percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras
      and horses, respectively. When comparing the three species (average body weight:
      200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in
      line with the variation of body weight. However, the average neuronal size in the
      capybara deviates from this pattern in being larger than that of in the horse.
      The rat presented great interindividual variability in all the neuronal
      parameters. From the data in the literature and our new findings in the capybara
      and horse, we conclude that some correlations exist between average size of
      neurons and body size and between total number of neurons and body size. However,
      these correlations are only approximate and are based on averaged parameters for
      large populations of neurons: they are less likely to be valid if one considers a
      single quantitative parameter. Several quantitative features of the nervous
      tissue have to be taken into account together, rather than individually, when
      evolutionary trends related to size are considered.

PMID- 15235908
TI  - Early development of the pituitary gland in Acipenser naccarii (Chondrostei,
      Acipenseriformes): an immunocytochemical study.
AB  - The distribution and appearance of secretory cells in the pituitary gland were
      investigated for the first time in a chondrostean species, Acipenser naccarii,
      from embryos to juveniles, by immunohistochemistry with mammalian and teleost
      hormone antisera. On 5.5 day post-fertilization (2.5 days pre-hatching), the
      pituitary of embryos appears as an oval cell mass with a narrow central cavity
      (hypophysial cleft), close to the ventral border of diencephalon under the third
      ventricle. At that time no neurohypophysis is observed, the adenohypophysis is
      not yet structurally divided into pars intermedia (PI) and pars distalis (PD) and
      only immunoreactive growth hormone cells are detectable. Seven days post
      fertilization (1 day pre-hatching) the immunoreactive thyrotropic cells appear in
      the ventral region and the immunoreactive adrenocorticotropic cells in the
      posterior dorsal one. At hatching, some immunoreactive melanotropic (ir-MSH)
      cells are visible in the posterior dorsal region and some immunoreactive
      prolactin cells in the anterior one. Eight days later the immunoreactive
      somatolactin cells appear along the posterior dorsal border and the
      immunoreactive gonadotropic I (ir-GtH I) cells in the ventral region. Here, a few
      ir-GtH II cells finally appear in 76-86 day old juveniles. The gland elongates
      after hatching and in 8-day-old larvae two adenohypophysial regions are
      identified: a posterior (the presumptive PI) and an anterior one (the presumptive
      PD). In 156-166-day-old juveniles three regions (rostral and proximal pars
      distalis and pars intermedia) appear and a high number of ir-MSH cells are
      visible in the rostral region. The first protrusion of neurohypophysis into
      adenohypophysis is observed in 76-86-day-old juveniles and increases with age,
      branching into PI. The rostro-caudal distribution of the immunoreactive cells
      follows the spatial expression of the corresponding hormone gene families
      observed in zebra fish, suggesting similar differentiating mechanisms in teleosts
      and chondrosteans.

PMID- 15235909
TI  - Control of the temporal and spatial Uncx4.1 expression in the paraxial mesoderm
      of avian embryos.
AB  - Uncx4.1 is a homeobox containing transcription factor that determines the
      development of the pedicles of the neural arches, transverse processes and
      proximal ribs. In this paper we characterize the expression pattern of Uncx4.1
      during chick embryogenesis with special focus on its expression in the paraxial
      mesoderm. In the presomitic mesoderm, Uncx4.1 is expressed in the caudal halves
      of the somites I and II. In the newly formed somites, Uncx4.1 expression remains
      in the caudal somite halves but becomes restricted to the somitocoele and the
      ventral epithelial wall. After somite compartmentalization, Uncx4.1 is expressed
      in the caudal half of the sclerotome in a well defined spatial and temporal
      pattern. Micromanipulations revealed that Uncx4.1 expression in the presomitic
      mesoderm is independent of signals from the axial structures and presumably
      induced by the intrinsic Notch/Delta driven oscillator activity that determines
      craniocaudal somite polarity. In contrast, in the maturing somite Uncx4.1
      expression depends on signals from the axial structures. The notochord-floor
      plate complex is essential for maintaining Uncx4.1 expression in the caudal
      somite half. The neural tube is necessary for providing sufficient Uncx4.1
      positive sclerotomal material to enable development of pedicles of the neural
      arches and transverse processes.

PMID- 15235910
TI  - Analysis of chromosome-11 aberrations in pulmonary and gastrointestinal
      carcinoids: an array comparative genomic hybridization-based study.
AB  - Carcinoid tumors are a heterogeneous group of neoplasms arising from the diffuse
      neuroendocrine system. Pulmonary as well as gastrointestinal carcinoids can be
      separated into those with low malignant and intermediate malignant potential. DNA
      losses of chromosome arm 11q are commonly seen in pulmonary neuroendocrine
      tumors. Conflicting results have been published comparing atypical with typical
      lung carcinoids with respect to imbalances of chromosome 11. In the present
      study, a DNA microarray with genomic clones mapped to chromosome 11 was created,
      and array comparative genomic hybridization (CGH) with DNA derived from formalin
      fixed, paraffin-embedded tissue was performed. We investigated 4 typical and 12
      atypical carcinoids of the lung and, for comparison, 9 gastrointestinal
      carcinoids and 6 endocrine pancreatic tumors. We have shown that formalin-fixed,
      paraffin-derived DNA can be successfully used for array CGH. Alterations of 11q
      were rarely detected not only in typical carcinoids of the lung but also in
      gastrointestinal carcinoids. Atypical lung carcinoids that comprised extensive
      DNA losses also presented retained fragments in between these deleted regions.
      The array CGH data were consistent with the data of a previously published
      classical CGH study and were additionally confirmed using fluorescence in situ
      hybridization in the present investigation.

PMID- 15235911
TI  - Myxoid adrenocortical adenoma with a pseudoglandular pattern.
AB  - Myxoid changes rarely occur in adrenocortical adenomas and carcinomas. Only eight
      benign tumours with such features have been described thus far, five of which
      also had a prominent pseudoglandular component. We report an additional
      pseudoglandular myxoid adenoma of the adrenal gland detected in a 58-year-old
      male patient who developed mild hypertension. At surgery, a 4-cm mass was
      resected and found to contain cords and tubules of polygonal cells in a myxoid
      background. Limited areas of classical adrenocortical adenoma were detected in
      less than 20% of the tumour area. Lack of atypias and absence of mucin markers,
      together with an immunophenotype consistent with adrenal tumours (focal
      cytokeratin, vimentin, synaptophysin and alpha-inhibin immunoreactivities), led
      to a diagnosis of primary adrenocortical adenoma with an extensive
      pseudoglandular myxoid pattern. However, the differential diagnosis from
      metastatic well-differentiated adenocarcinomas, chordomas and retroperitoneal
      myxoid mesenchymal tumours (e.g. liposarcoma) may be difficult in the absence of
      a complete clinical history and a reliable immunoprofile. We strongly recommend
      staining of any myxoid or glandular tumour of the adrenal gland for alpha-inhibin
      and synaptophysin (probably the currently best characterised markers of
      adrenocortical origin) before considering alternative (probably more common)
      diagnoses of metastatic adenocarcinoma or retroperitoneal tumours localised to
      the adrenal gland.

PMID- 15235912
TI  - The role of temporal and spatial factors in the covert orienting of visual
      attention tasks.
AB  - There is a biphasic pattern in response times to peripheral uninformative cues,
      with faster responses to targets in cued locations when the stimulus onset
      asynchrony (SOA) is under 300 ms and slower responses when it is over 300 ms. The
      effect has typically been attributed entirely to the SOA while ignoring other
      aspects of the cues (duration, spatial configuration). To examine these other
      factors, along with SOA, the present experiments included manipulations of SOA
      (50, 100, 200, 400, 800 ms), inter-stimulus interval (ISI; 0, 50, 100, 150, 200,
      300, 350, 400, 500, 600, 700, and 750 ms), and whether or not the cue and target
      overlap in the same space. The results indicate that cueing effects depend on the
      combination of cue duration, ISI, SOA, and the spatial configuration of the cues
      and targets. Three factors are used to explain these time course results.

PMID- 15235913
TI  - Effector dependent sequence learning in the serial RT task.
AB  - At least five earlier studies could not find effector-dependent learning in the
      keying version of the serial reaction time (RT) task. Experiment 1 examined
      whether effector-dependent learning occurs when participants practice the serial
      RT task with three fingers of one hand for about 1,300 sequence repetitions
      instead of the more common 50-100 repetitions. The results confirm that,
      following extended practice, sequence learning produces an effector-dependent
      component. Specifically, an unpracticed hand executed a practiced sequence slower
      than a practiced hand. However, Experiment 2 showed that effector-dependent
      sequence learning develops only when fingers of one hand are used, suggesting
      that effector-dependent sequence learning involves adjustment to the mechanical
      interactions between the fingers of one hand. In addition, when sequences had
      been practiced with one hand, mirror versions of the practiced sequences in both
      experiments showed moderate transfer. But when practiced with two hands no
      transfer to a mirrored version of the sequence was observed. This suggests that
      only practice with one hand produces a representation that facilitates the
      execution of mirror sequences. Generally, the same results were found in more or
      less aware participants, congruent with the idea that the effector-dependent
      representation and the representation allowing transfer to mirror sequences are
      implicit.

PMID- 15235914
TI  - Stimulation of Xenopus P2Y1 receptor activates CFTR in A6 cells.
AB  - Nucleotide binding to purinergic P2Y receptors contributes to the regulation of a
      variety of physiological functions in renal epithelial cells. Here, we
      investigate the regulatory mechanism of the P2Y1 receptor agonist 2
      methylthioadenosine diphosphate (2-MeSADP) on Cl- transport in A6 cells, a
      commonly used model of the distal section of the Xenopus laevis nephron. Protein
      and mRNA expression analysis together with functional measurements demonstrated
      the basolateral location of the Xenopus P2Y1 receptor. 2-MeSADP increased
      intracellular [Ca2+] and cAMP and Cl- efflux, responses that were all inhibited
      by the specific P2Y1 receptor antagonist MRS 2179. Cl- efflux was also inhibited
      by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker
      glibenclamide. Inhibition of either protein kinase A (PKA) or the binding between
      A-kinase-anchoring proteins (AKAPs) and the regulatory PKA RII subunit blocked
      the 2-MeSADP-induced activation of CFTR, suggesting that PKA mediates P2Y1
      receptor regulation of CFTR through one or more AKAPs. Further, the truncation of
      the PDZ1 domain of the scaffolding protein Na+/H+ exchanger regulatory factor-2
      (NHERF-2) inhibited 2-MeSADP-dependent stimulation of Cl- efflux, suggesting the
      involvement of this scaffolding protein. Activation or inhibition of PKC had no
      effect per se on basal Cl- efflux but potentiated or reduced the 2-MeSADP
      dependent stimulation of Cl- efflux, respectively. These data suggest that the X
      laevis P2Y1 receptor in A6 cells can increase both cAMP/PKA and Ca2+/PKC
      intracellular levels and that the PKC pathway is involved in CFTR activation via
      potentiation of the PKA pathway.

PMID- 15235915
TI  - Effects of dopamine on ion transport across the rat distal colon.
AB  - Dopamine (5.10(-6)-5.10(-4) M) induced a concentration-dependent decrease in
      short-circuit current (I(sc)) across the rat distal colon. This response was
      preceded by a transient and inconsistent increase in I(sc). The alpha
      adrenoceptor blocker phentolamine and the inhibitors of dopamine-2-like (D(2)
      like) receptors L-741,626 and L-745,870 inhibited the dopamine response,
      suggesting a contribution of adrenergic and dopaminergic receptors. The decrease
      in I(sc) evoked by dopamine was inhibited by bumetanide, an inhibitor of the
      basolateral Na(+)-K(+)-2 Cl(-) cotransporter responsible for the uptake of K(+),
      and by quinine, a blocker of apical K(+) channels, indicating that stimulation of
      K(+) secretion contributes to the measured change in I(sc). In patch-clamp
      experiments dopamine hyperpolarized the membrane and increased cellular K(+)
      current. This response was not concomitant with a change in the intracellular
      [Ca(2+)] as demonstrated in parallel fura-2 experiments. These results
      demonstrate that dopamine, like other catecholamines, stimulates colonic K(+)
      secretion.

PMID- 15235916
TI  - Laparoscopic Nissen repair: indications, techniques and long-term benefits.
AB  - BACKGROUND: The Nissen fundoplication or total 360 degrees fundoplication is
      probably the most frequently used anti-reflux procedure throughout the world.
      With the advent of laparoscopic surgery the popularity among surgeons to perform
      a laparoscopic Nissen fundoplication has even increased. AIM: The purpose of this
      paper is to provide an overview of the experience of laparoscopic Nissen
      fundoplication over the past 15 years. METHOD: We performed an extensive review
      of the literature in order to ascertain the representative papers. In addition,
      available consensus papers, especially with regard to indication and technique,
      were assessed. Indication for a laparoscopic Nissen fundoplication should depend
      on documentation of the presence of disease as well as objective testing of the
      functional disorders and the complications. The technique of Nissen
      fundoplication is discussed controversially. Consensus exists with regard to
      floppiness of the wrap, necessary closure of the crurae and the use of a
      calibration method during the performance of the wrap. RESULTS: The laparoscopic
      technique creates a learning curve, which needs to be respected. Large
      prospective series in recent years have shown a complication rate between 5% and
      10%, depending on the definition of the complication. In these last prospective
      series good and excellent results have been reported, of between 85% and 95%.
      Reflux recurrence is reported as between 1% and 8.5%, with a concomitant
      dysphagia rate of 0%-10%. CONCLUSIONS: The Nissen fundoplication is currently
      performed throughout the world, most frequently in a minimally invasive
      technique. Several randomized trials that have been performed in the past years
      document that the Nissen fundoplication is an effective procedure for the
      treatment of pathological gastro-oesophageal reflux disease when a critical
      indication is used for well-defined patients.

PMID- 15235918
TI  - Arsenic exposure and human papillomavirus response in non-melanoma skin cancer
      Mexican patients: a pilot study.
AB  - We assessed the relationships between chronic arsenic (As) exposure, human
      papilloma virus (HPV) contact and non-melanoma skin cancer (NMSC) by means of a
      dermatology clinic-based case-control study (42 cases and 48 controls) in Region
      Lagunera, Mexico, where chronic As poisoning is endemic. Exposure was determined
      through detailed history of residence in the As-contaminated area and measurement
      of As levels in drinking water and urine. We used a consensus epitope from the
      central region of L1 protein of the HPV family to determine antibodies against
      HPV. A history of As exposure and HPV seropositivity were associated with
      increased NMSC risks. A history of exposure to high levels of As increased the
      risk for NMSC (OR = 4.53; P = 0.11) in the group of seronegative HPV patients. A
      positive response to HPV significantly increased the OR for NMSC to 9.04 (P =
      0.01) when history showed exposure to low levels of As. Interestingly, the OR was
      significantly increased to 16.5 (P = 0.001) when both exposure to high levels of
      As and HPV seropositivity were present. In addition, the presence of NMSC
      increased the OR (5.45; P = 0.03) for a positive response to HPV when history
      showed exposure to low levels of As, but the OR was increased to 8.0 (P = 0.005)
      in the cases with high exposure levels. Thus, HPV infection could constitute an
      additional risk factor for NMSC development in humans chronically exposed to As.
      However, further studies with additional populations are needed to determine the
      interaction between HPV and As exposure in NMSC.

PMID- 15235919
TI  - Sudden cardiac death due to hypersensitivity myocarditis during clozapine
      treatment.
AB  - The case concerns the sudden death of a 29-year-old male during clozapine therapy
      started 2 weeks before. He had a history of treatment-resistant chronic
      schizophrenia. A complete immunohistochemical study was performed on heart
      specimens. Histologically, the heart presented diffuse eosinophilic infiltrates
      located around perivascular structures and focal myocyte necrosis with numerous
      interstitial eosinophils admixed with histiocytes. The diagnosis of acute
      myocarditis with an eosinophilic infiltrate was established as the cause of
      death. The autopsy findings and a detailed medical history supported the
      conclusion that clozapine-induced hypersensitivity myocarditis was the most
      likely cause of death.

PMID- 15235920
TI  - Food transfer between chimpanzee mothers and their infants.
AB  - Food sharing among chimpanzees is known to occur particularly between mothers and
      infants and has been proposed to be a form of parental investment. To explore the
      function of food sharing, it is essential to know how and what is transferred to
      an infant from its mother. We investigated details of interactions leading to
      food transfer and characteristics of items transferred in three mother-infant ( <
      2 years old) pairs in captivity. We gave one kind of fruit or vegetable to a
      mother and observed interactions between the mother and her infant. Tested items
      consisted of familiar and novel foods for infants. Two patterns of direct food
      transfer, so-called sharing, were recognized: (1) "infant-initiated sharing" in
      which the infant attempted to take food and the mother did not resist, and (2)
      "mother-initiated sharing" in which the mother spontaneously offered a part of
      her food without the infant's attempts to take it. There were clear differences
      in the characteristics of items transferred in these two patterns of sharing. In
      infant-initiated sharing, palatable parts of the same food that the mother was
      eating were transferred. In contrast, in mother-initiated sharing, only
      unpalatable parts of food in the mother's possession were transferred. Mothers
      seemed to be reluctant to give nutritious foods to their infants during this
      study period. Infants, rather than mothers, were responsible for initiating and
      experiencing the diversity of adult foods in chimpanzees.

PMID- 15235921
TI  - Floral ontogeny in Lespedeza thunbergii (Leguminosae: Papilionoideae:
      Desmodieae): variations from the unidirectional mode of organ formation.
AB  - Floral ontogeny of Lespedeza thunbergii was studied with the use of scanning
      electron microscopy (SEM). The ontogeny varies in all whorls from the
      undirectional mode, which has been long held to be the rule in Leguminosae. In
      the sepal whorl, the lateral and the adaxial sepals are formed simultaneously,
      which is interpreted as a tendency towards whorled organ formation. Whorled organ
      formation is shown in the petal whorl. The antesepalous stamen whorl varies least
      from the unidirectional mode. Here, the adaxial stamens are formed successively.
      This is seen as a remnant of an original helical organ formation in
      Papilionoideae. Within the antepetalous stamen whorl, the two abaxial stamens and
      the adaxial stamen are formed first, followed by the two lateral stamens. This is
      a rarely found phenomenon, which is hard to interpret at the present state of
      knowledge. Concerning the mature flower, it is shown that nectar stomata are
      found in a distinct area on the adaxial side of the flower. The presented "new"
      characteristics should be an initial step toward further work on taxa of the
      tribe Desmodieae. These studies will broaden the data set and enable a detailed
      phylogenetic analysis.

PMID- 15235922
TI  - 4-Coumarate:coenzyme A ligase in black locust (Robinia pseudoacacia) catalyses
      the conversion of sinapate to sinapoyl-CoA.
AB  - 4-Coumarate:coenzyme A (CoA) ligase (4CL, EC 6.2.1.12) in crude enzyme
      preparation from the developing xylem of black locust (Robinia pseudoacacia)
      converted sinapate to sinapoyl CoA. The sinapate-converting activity was not
      inhibited by other cinnamate derivatives, such as p-coumarate, caffeate or
      ferulate, in the mixed-substrate assay. The crude extract prepared from the
      developing xylem was separated by anion-exchange chromatography into three
      different 4CL isoforms. The isoform 4CL1 had a strong substrate preference for p
      coumarate, but lacked the activity for ferulate and sinapate. On the other hand,
      4CL2 and 4CL3 displayed activity toward sinapate and also possessed high activity
      toward caffeate as well as p-coumarate. The crude extract from the shoots
      exhibited a very similar substrate preference to that of the developing xylem;
      therefore, 4CL2 may be a major isoform in both crude enzyme preparations. These
      results support the hypothesis that sinapate-converting 4CL isoform is
      constitutively expressed in lignin-forming cells.

PMID- 15235923
TI  - Crystal-induced inflammation of the kidneys: results from human studies, animal
      models, and tissue-culture studies.
AB  - Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the
      most common crystals seen in the kidneys. Most of the crystals evoke an
      inflammatory response leading to fibrosis, loss of nephrons, and eventually to
      chronic renal failure. Of the three, CaOx monohydrate is the most reactive,
      whereas some forms of CaP do not evoke any discernible response. Reactive oxygen
      species are produced during the interactions between the crystals and renal cells
      and are responsible for the various cellular responses. CaOx crystals generally
      form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals
      results in the increased synthesis of osteopontin, bikunin, heparan sulfate,
      monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are
      known to participate in inflammatory processes and in extracellular matrix
      production. CaOx crystal deposition in rat kidneys also activates the renin
      angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen
      activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form
      in the tubular lumen, tubular cells, or tubular basement membrane. Renal
      epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and
      calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate
      production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP)
      while down-regulating the production of inhibitors of MMPs through activation of
      p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with
      renal tubular atrophy, interstitial fibrosis, and development of inflammatory
      infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1
      as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor
      necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8
      is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and
      nuclear transcription factors activated protein 1 and nuclear factor kappabeta.
      Urate crystals also stimulate the macrophages to produce MMPs.

PMID- 15235924
TI  - Factors influencing long-term survival in patients on chronic dialysis.
AB  - Japan has the highest prevalence of dialysis patients in the world. According to
      the Annual Report of the Japanese Society for Dialysis Therapy (JSDT; 2002), the
      total dialysis population was 229 538 (1801.5 patients per million population) at
      the end of 2002. The annual crude mortality rate has been less than 10%. Survival
      rates in the incident dialysis patients were 0.874 for 1 year, 0.609 for 5 years,
      and 0.391 for 10 years. Despite the increased acceptance for dialysis of elderly
      patients, those with comorbid conditions, and those with diabetes mellitus, the
      adjusted hazard ratios for death have been improving since 1983. This improvement
      was obtained by delivering a dialysis dose of Kt/V 1.33 and dialysis sessions of
      4 h. Independently of the JSDT registry, there exists a local dialysis registry
      in Okinawa, the Okinawa Dialysis Study (OKIDS) registry, in which are filed the
      records of every chronic dialysis patient from the beginning of dialysis therapy
      in 1971 to the end of 2000. Several outcome studies have been conducted to
      determine the factors related to survival, using the data in that registry. There
      are distinct differences in environmental and socioeconomic conditions and
      lifestyles within a given country, and between countries and ethnic groups, that
      may affect the survival of dialysis patients. In this article, both the JSDT
      registry and OKIDS data are reviewed in order to identify factors related to the
      survival of chronic dialysis patients.

PMID- 15235925
TI  - Role of potassium in hypokalemia-induced hyponatremia: lessons learned from the
      Edelman equation.
AB  - It is well known that changes in the mass balance of K+ can lead to an alteration
      in the plasma water sodium concentration ([Na+]pw). We have recently shown that
      based on the Edelman equation, the [Na+]pw is determined by the total
      exchangeable Na+ (Nae), total exchangeable K+ (Ke), total body water (TBW),
      osmotically inactive Nae and Ke, plasma water [K+], intracellular and
      extracellular osmotically active non-Na+ and non-K+ osmoles, and plasma
      osmotically active non-Na+ and non-K+ osmoles. In light of these findings, a re
      analysis of the role of K+ in modulating the [Na+]pw is required in understanding
      the pathophysiology of hypokalemia-induced hyponatremia. In this article, we
      characterize the complex role of K+ in the pathogenesis of hypokalemia-induced
      hyponatremia using a three-compartment model and the known parameters in the
      Edelman equation. Our analysis indicates that K+ modulates the [Na+]pw by
      changing Ke in addition to the parameters in the y-intercept of the Edelman
      equation. Moreover, the magnitude of potassium-induced changes in the [Na+]pw is
      determined by the pathophysiologic mechanisms by which changes in Ke occur.

PMID- 15235926
TI  - Skim soy protein enhances GFR as much as beefsteak protein in healthy human
      subjects.
AB  - BACKGROUND: It has been reported that an acute load of beefsteak (200 g)
      significantly enhanced the glomerular filtration rate (GFR; inulin clearance and
      creatinine clearance) in healthy human subjects compared to that in the same
      subjects in the fasted state. However, no comparative study of the effects of the
      same amount of vegetable protein on GFR has been reported to date. METHODS: We
      attempted to compare changes in the GFR (inulin clearance and creatinine
      clearance) in six healthy male subjects following consumption of the same amount
      of beefsteak or baked skim soy with soy sauce (protein, 86.9 g) after fasting.
      The clearance study was performed by conventional methods. Inulin was measured by
      the anthrone method. Creatinine was measured by the Jaffe rate assay method.
      Amino-acid analysis of the beefsteak and baked skim soy with soy sauce was done
      by acid or hydroxide hydrolysis and an amino-acid analyzer. RESULTS: A
      significant enhancement of the GFR (both inulin clearance and creatinine
      clearance) was observed following acute loading with beefsteak or baked skim soy
      with soy sauce, compared to the GFR in the fasted state. No significant
      difference was observed between the results with beefsteak and the results with
      baked skim soy with soy sauce. Amino-acid analysis revealed that the total amount
      of three amino acids (glycine, alanine, and arginine; or serine, alanine, and
      proline) was almost identical in beefsteak (animal protein) and baked skim soy
      with soy sauce (vegetable protein). CONCLUSIONS: The present study demonstrated
      that vegetable protein with the same amino-acid composition could enhance the GFR
      in healthy subjects as much as animal protein.

PMID- 15235927
TI  - Applicability of steroid therapy in 275 adult patients with IgA nephropathy
      determined using a histological scoring system and degree of proteinuria.
AB  - BACKGROUND: The purpose of this study was to propose clinical and pathologic
      criteria for the indication for steroid therapy (ST) in adult IgA nephropathy
      (IgAN). METHODS: We analyzed 275 adult IgAN patients retrospectively, using a
      histological scoring system. The histological score was expressed by evaluating,
      semiquantitatively, the extent of glomerular and tubulointerstitial lesions in
      terms of the activity index (AI) and chronicity index (CI). To determine the
      applicability of ST, three groups were categorized by evaluating the statistical
      significance of the correlation between the AI and CI, together with the daily
      amount of urinary protein (UP) and the outcome. RESULTS: In group A, which had a
      CI > or = 5 alone, 33 out of 43 patients showed a decline in renal function.
      There was no statistically significant difference between the subgroup with ST
      and that without ST. In group B, which had CI < 5, AI < 5, and UP < 1.0 g/day,
      169 out of 174 patients had normal renal function irrespective of whether or not
      they received ST. Thus, ST had no beneficial effects in group A and B patients.
      In group C, which had CI < 5 and AI > or = 5 or UP > or = 1.0 g/day, patients
      with ST had a significantly higher incidence of an outcome with normal renal
      function (22 out of 24 patients) than that in patients without ST (19 out of 34
      patients) (P < 0.01). Thus, ST had beneficial effects in group C patients.
      CONCLUSIONS: . We propose that a histological criterion be used in combination
      with the degree of proteinuria as an indication for ST in adult IgAN patients.

PMID- 15235928
TI  - A randomized open-label comparative study of conventional therapy versus
      mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome
      (postmarketing survey).
AB  - BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs
      placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ
      was more effective than placebo in reducing the rate of deterioration of renal
      function. The present study was conducted to evaluate the efficacy and safety of
      MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter
      randomized open-label controlled trial in patients with SRPNS was conducted as a
      2-year prospective postmarketing study. RESULTS: There was a significant
      imbalance in the baseline serum albumin level (s-Alb) between the conventional
      therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in
      the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl.
      Therefore, the primary analysis (urinary protein level (UP)-improving effect) was
      performed using a mixed-effects model, with stratification according to the
      baseline s-Alb value. The analysis revealed that, in the subset of 34 patients
      with membranous nephropathy (MN) within the stratum of patients with baseline s
      Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP
      level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the
      MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the
      stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no
      significant differences in the UP between the two treatment groups. Hence, MZ
      onlay therapy was not considered to be efficacious in this group of patients. No
      serious adverse reactions to the drug were observed. CONCLUSIONS: The present
      study yielded significant results, in that it suggested the possibility that long
      term MZ therapy may afford further reduction of the UP, in addition to that
      obtained following CT, in particular, in MN patients in a severe nephrotic state.

PMID- 15235929
TI  - Renal function at the time of renal biopsy as a predictor of prognosis in
      patients with primary AL-type amyloidosis.
AB  - BACKGROUND: Amyloid light-chain (AL)-type amyloidosis is a plasma cell disorder
      with a poor prognosis for survival. Although prognostic factors, such as the
      number of organs involved and heart function or failure in respond to therapy
      have been clarified based on studies including a large series of patients, there
      are large interindividual differences in the prognosis of patients with primary
      AL-type renal amyloidosis. METHODS: To clarify the prognostic factors of AL-type
      renal amyloidosis, we retrospectively investigated the clinical manifestations,
      histopathological data, and prognosis of 21 patients with amyloidosis, who had
      been diagnosed by renal biopsy. RESULTS: Eleven patients died, at a mean
      observational time of 21.7 months after renal biopsy, whereas the mean
      observational time was 51.0 months for the 10 patients who survived. The
      creatinine clearance rate was significantly higher, and the serum creatinine
      concentration and the grade of interstitial damage were significantly lower in
      surviving patients (P < 0.05). The presence of amyloid fibrils in organs other
      than the kidney did not influence prognosis for survival. However, the
      intraventricular septum was thinner in surviving patients (P < 0.1). Thirteen
      patients had undergone melphalan-prednisolone therapy, but it did not affect
      prognosis for survival. Cox proportional hazard regression analysis revealed that
      the renal function at the time of diagnosis was a significant and independent
      prognostic factor for survival. CONCLUSIONS: Our study demonstrated that renal
      function at the time of biopsy and renal interstitial damage are the best
      predictors of survival in AL-type renal amyloidosis.

PMID- 15235930
TI  - Suppression of parathyroid hormone secretion in CAPD patients by intraperitoneal
      administration of Maxacalcitol.
AB  - BACKGROUND: Maxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue.
      In previous clinical studies, OCT was administered three times a week to
      hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in
      whom it acted by inhibiting parathyroid hormone secretion, as well as causing
      mildly elevated serum calcium. However, intravenous injection of OCT, which
      requires frequent visits to the outpatient clinic, degrades the quality of life
      of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise
      visit the clinic only once or twice per month. In the present study, we
      investigated whether transperitoneal absorption of OCT inhibited intact
      parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the
      peritoneal dialysis fluid. METHODS: Peritoneal dialysis fluid containing 20 micro
      g of OCT was injected into the peritoneal cavity of five CAPD patients. The serum
      and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured
      before and after treatment. RESULTS: The mean concentration of OCT in peritoneal
      dialysis fluid rapidly decreased, from 25268.0 pg/ml at 0 h to 1694.0 pg/ml at 2
      h and 44.9 pg/ml at 4 h. In contrast, the mean serum OCT level increased from the
      pretreatment level, which was below the detection limit of the assay, to 656.0
      pg/ml at 0.5 h and a peak of 759.0 pg/ml at 1 h, and thereafter gradually
      decreased, to 713.8 pg/ml at 2 h and 555.8 pg/ml at 4 h. Mean i-PTH significantly
      decreased, to 83.9% of the baseline level, at 1 h (P < 0.05) and thereafter
      stayed at around 90%. No consistent trends in calcium and phosphate levels were
      observed in the five patients. CONCLUSIONS: By injecting OCT into the peritoneal
      cavity, i-PTH levels could be significantly decreased. These findings indicate
      the therapeutic efficacy of intraperitoneal administration of OCT for CAPD
      patients.

PMID- 15235931
TI  - Simulation of post-dialysis urea rebound using regional flow model.
AB  - BACKGROUND: A regional flow model (RFM) can establish the missing link between
      hemodynamics and solute removal. We tried to simulate post-dialysis urea rebound
      using a RFM for the purpose of evaluating the validity of this model. METHODS:
      Eight patients on maintenance hemodialysis with negligible renal function were
      investigated. The parameters of the RFM were estimated so as to fit the
      calculated values of urea nitrogen to the measured values during a dialysis
      session. The estimated parameters were total urea distribution volume (TUV),
      systemic blood flow (Qsys), flow fraction (fQH) and volume fraction (fVH) of the
      high-flow system. Thirteen types of parameter sets were used for the estimation.
      The urea rebound at 60 min after a dialysis session (Creb) and the rebound ratio
      (RR) were calculated using these estimated parameters. The accuracy of the
      calculated Creb and RR was assessed. RESULTS: The accuracy of Creb and RR
      determined using estimated TUV, by taking Qsys as systemic blood flow calculated
      from ultrasonic echo cardiogram (Qucg), fQH as 0.8, and fVH as 0.2, was
      insufficient (method 1a). The accuracy of these values was significantly
      increased by taking fQH as 0.85 (method 1b). The estimation of Qsys with TUV did
      not improve the accuracy of Creb and RR (methods 2a and 2b). The estimation of
      fQH, fVH, and TUV (method 8) increased the accuracy of Creb and RR significantly
      compared with method 1a, but not compared with method 1b. Even with method 1b or
      method 8, the percentage RR was less than 90% in two patients. CONCLUSIONS: By
      taking fQH as 0.85, an acceptably accurate simulation of urea rebound can be
      accomplished with the necessity to estimate only TUV. The simulation was not
      significantly improved by the estimation of Qsys, fQH, and fVH. The RFM is useful
      in practice, although it has some limitations.

PMID- 15235932
TI  - Two cases of congenital nephrotic syndrome.
AB  - The clinical course and renal histological changes in two patients with
      congenital nephrotic syndrome are presented. Both patients developed edema and
      proteinuria at 2 days of age. Steroids and immunosuppressive drugs were not used
      in either patient. One patient showed gradual disappearance of nephrotic syndrome
      and proteinuria during the 16-month follow-up. In the other patient, the
      nephrotic state persisted and nephrotic complications necessitated bilateral
      nephrectomy when she was 12 months old. Renal biopsy showed minimal change
      lesions in one patient, while the nephrectomized kidneys showed mild mesangial
      proliferation and matrix increase in the glomeruli. No tubular dilatation or
      microcysts were observed in either patient.

PMID- 15235933
TI  - Severe hyperreninemic hypertension associated with spontaneous renal cholesterol
      crystal embolization.
AB  - A 70-year-old man was admitted because of severe hypertension and renal
      insufficiency. Marked elevation in plasma renin activity (PRA; 34.2 ng/ml per h)
      was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and
      panperitonitis, went into shock, and died. An autopsy revealed severe
      atherosclerosis with marked ulceration in the abdominal aorta. Renal histology
      showed multiple cholesterol crystal embolization (CCE) associated with
      infarction. Cholesterol crystals were also detected in the vessels of the
      gastrointestinal system, including the liver, stomach, colon, and pancreas.
      Although not common, spontaneous CCE should be considered in elderly patients who
      present with abrupt onset of severe hypertension associated with renal
      insufficiency. The most important finding in this patient was severe
      hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system
      is the suggested mechanism for the hypertension in renal CCE, we could not find
      any reported case of renal CCE with hyperreninemia. It is reasonable to consider
      that severe hyperreninemia might be overlooked in renal CCE. PRA should be
      measured in patients with renal CCE, because it may give important information
      for selecting antihypertensive agents and improving the prognosis. To clarify
      this possibility, an accumulation of similar cases is necessary.

PMID- 15235934
TI  - Metal stent placement for two patients with post-transplantation renal artery
      stenosis, using intravascular ultrasound imaging.
AB  - Post-transplantation renal artery stenosis is recognized at relatively early
      periods after renal transplantation. We report herein our experience of utilizing
      transluminal expanded metal stents (Palmaz stent and Wall stent) for post
      transplantation renal artery stenosis, and monitoring with intravascular
      ultrasound (IVUS) imaging. The recipients were a 51-year-old woman (case 1) and a
      57-year-old man (case 2), and the grafts were procured from cadaveric donors.
      Renal function had deteriorated suddenly at 5 months after renal transplantation
      in case 1 and at 86 months in case 2. The cause of the graft dysfunction was
      renal arterial stenosis. Color doppler ultrasound imaging and angiography
      diagnosed post-transplantation renal artery stenosis. The renal artery stenosis
      was serious, being greater than 90% in both patients. Percutaneous transluminal
      angioplasty (PTA) was performed, but its effectiveness was not sufficient;
      therefore, an indwelling endoluminal metallic Palmaz stent and an indwelling Wall
      stent were placed at the sites of stenosis while monitoring was done with IVUS.
      No complications were recognized at all. The length and degree of stenosis
      location became clear by using IVUS, and suitable stents could be selected for
      the renal artery stenosis. The clinical effect was excellent; the renal function
      improved to the pre-hospitalization value. We conclude that the Palmaz stent and
      the Wall stent were useful as a noninvasive strategy for treating post
      transplantation renal artery stenosis. This procedure could be performed safely
      and surely using IVUS.

PMID- 15235935
TI  - Aplastic anemia associated with initiation of nizatidine therapy in a
      hemodialysis patient.
AB  - We report on a hemodialysis (HD) patient in whom fatal aplastic anemia developed
      after the administration of nizatidine, a histamine 2 (H2)-receptor antagonist.
      The patient was a 55-year old Japanese woman and had been on HD for 2 years due
      to endstage diabetic nephropathy. The patient had a hemorrhagic duodenal ulcer
      and had been treated with lansoprazole, a proton pump inhibitor, for 2 months.
      After improvement, lansoprozole was discontinued and she was subsequently treated
      with nizatidine. Twelve days after initiation of nizatidine treatment, the
      patient developed a high-grade fever with symptoms suggestive of upper
      respiratory infection. Hematological tests showed severe pancytopenia, and drug
      induced aplastic anemia was diagnosed. Nizatidine was suggested as the causal
      drug. Despite intensive therapies, the patient died on the 23rd hospital day from
      generalized fungal infections. Although hematological adverse events have been
      reported in HD patients receiving H2-receptor antagonists, few studies of fatal
      aplastic anemia associated with these drugs have been reported. This case
      emphasized that careful observation is required after the initiation of H2
      receptor antagonist treatment in HD patients.

PMID- 15235936
TI  - The beneficial effect of effective control of anemia on hyperinsulinemia and
      hypoxemia in a hemodialysis patient with corrected transposition of the great
      arteries.
AB  - We report the beneficial effect of control of anemia on hyperinsulinemia and
      hypoxemia in a hemodialysis patient with corrected transposition of the great
      arteries. The patient's hemoglobin (Hb) level of 10.3 g/dl on admission
      represents good control for hemodialysis (HD) patients, but it was too low for
      this patient with secondary polycythemia because of a right-to-left shunt.
      Control of anemia for a 10-month period was followed by a marked increase in Hb
      level (from 10.3 g/dl to 13.9 g/dl) and in aerobic work capacity, while the
      fasted insulin level decreased from 36.7 microU/ml to 8.0 microU/ml, without
      changes in leptin level, body mass index (BMI), fat mass, Kt/V, or protein
      catabolic rate (PCR). Additionally, hypoxemia was ameliorated, from PO2 33.1 mmHg
      to PO2 56.2 mmHg, and the hyperdynamic cardiac state was improved. The degree of
      anemia, together with deteriorating tissue oxygenation, may have predisposed this
      patient to developing insulin resistance and consequent hyperinsulinemia. The
      most appropriate target Hb concentration should be tailored for the clinical
      condition of each individual patient, bearing in mind an insulin-resistance
      state, especially in hemodialysis patients with hypoxemia. A more complete
      understanding of what regulates insulin resistance and consequent
      hyperinsulinemia in endstage renal disease (ESRD) awaits the elucidation of
      carbohydrate and insulin metabolism.

PMID- 15235937
TI  - Type of anaesthesia and patient acceptance in groin hernia repair: a multicentre
      randomised trial.
AB  - BACKGROUND: Groin hernia repair can be performed under general (GA), regional
      (RA), or local (LA) anaesthesia. This multicentre randomised trial evaluates
      patient acceptance, satisfaction, and quality of life with these three
      anaesthetic alternatives in hernia surgery. METHODS: One hundred and thirty-eight
      patients at three hospitals were randomised to one of three groups, GA, RA, or
      LA. Upon discharge, they were asked to complete a specially designed
      questionnaire with items focusing on pain, discomfort, recovery, and overall
      satisfaction with the anaesthetic method used. The global quality-of-life
      instrument EuroQol was used for estimation of health perceived. RESULTS:
      Significantly more patients in the LA group than in the RA group felt pain during
      surgery ( P<0.001). This pain was characterised as light or moderate and for the
      majority of LA patients was felt during infiltration of the anaesthetic agent.
      Postoperatively, patients in the LA group first felt pain significantly later
      than patients in the other two groups ( P=0.012) and significantly fewer LA
      patients consumed analgesics more than three times during the first postoperative
      day ( P=0.002). The results concerning nausea, vomiting, and time to first meal
      all favour LA. No difference was found among the three groups concerning overall
      satisfaction and quality of life. CONCLUSION: In a general surgical setting, we
      found LA to be well tolerated and associated with significant advantages compared
      to GA and RA.

PMID- 15235938
TI  - Reducing the pain of open groin hernia repair.
AB  - Pain after open mesh repair of groin hernia has a multifactorial etiology.
      Suturing technique for anchoring the mesh is important. Sutures placed too
      tightly, a common practice, are often the site of pain and point tenderness.
      These "pain points" are often precisely felt by patients and may vary in their
      intensity and duration. We believe that this type of suturing-technique-related
      pain can be significantly reduced by an "air-knotting" technique described below.
      The mesh was anchored with sutures tied in a subtle air-knot. In the event of
      accidentally incorporating a nerve in the knot, an air knot is less likely to
      cause the distressing symptoms of entrapment neuralgia. All knots are tied above
      the mesh and not across the edge of the mesh. Using this technique, we believe a
      significant reduction in the sharp, well-localized point pain can be achieved.

PMID- 15235939
TI  - Laparoscopic incisional and ventral hernia repair: complications-how to avoid and
      handle.
AB  - Complications will occur with any operative procedure. The possibility of this
      must be considered for laparoscopic incisional and ventral hernia repair (LIVH)
      as well. The most commonly reported of these include: intraoperative intestinal
      injury (1-3.5%), infection involving the prosthetic biomaterial (0.7-1.4%), (2.6
      100%), postoperative ileus seromas (1-8%), and persistent postoperative pain (1
      2%). The incidence of enterotomy can be reduced by careful dissection and
      judicious use of any energy source. Infection can be minimized by the use of
      perioperative antibiotics, an antimicrobially impregnated biomaterial, and
      careful manipulation of the prosthesis during the procedure. Seromas are so
      common that they should be expected but can be decreased by the use of a
      postoperative abdominal binder. Aspiration will be necessary in a few instances.
      Similarly, ileus is expected when there is significant bowel dissection and
      bleeding. Early ambulation and standard use of postoperative bowel care will aid
      in the treatment of this problem. Persistent pain will generally occur at the
      site of a transfascial suture. It cannot be predicted or prevented with
      certainty. When it occurs, local injection with bupivacaine, steroids, or non
      steroidal agents will help, but occasionally, removal of the offending suture(s)
      will be required. The average recurrence rate for LIVH is approximately 5.6% in
      the literature. Rates as high as 15.7%, however, have been reported. Recurrence
      will be increased by inadequate prosthetic overlap of the fascial defect,
      infection that involves the biomaterial, which then requires its removal, and
      lack of the use of transfascial sutures. To prevent these risks, the surgeon must
      assure that there is at least a 3-cm overlap of all portions of the hernia defect
      and insist that sutures are used at 5-cm intervals to fix the biomaterial.
      Infection that requires explantation of the patch will generally result in
      recurrence, as this must be repaired primarily. Alternatively, the use of a
      collagen prosthesis may allow immediate repair, but this is associated with a
      high failure rate. A staged repair will be necessary in the future in most
      patients.

PMID- 15235940
TI  - Extrinsic factors potassium chloride and glycerol induce thermostability in
      recombinant anthranilate synthase from Archaeoglobus fulgidus.
AB  - Thermostable anthranilate synthase from the marine sulfate-reducing
      hyperthermophile Archaeoglobus fulgidus has been expressed in Escherichia coli,
      purified, and characterized. The functional enzyme is an alpha2beta2
      heterotetrameric complex of molecular mass 150+/-15 kDa. It is composed of two
      TrpE (50 kDa) and two TrpG (18 kDa) subunits. The extrinsic factors glycerol
      (25%) and potassium chloride (2 M) stabilized the recombinant enzyme against
      thermal inactivation. In the presence of these extrinsic factors, the enzyme was
      highly thermostable, exhibiting a half-life of thermal inactivation of about 1 h
      at 85 degrees C. The kinetic constants for the enzyme under these conditions
      were: Km (chorismate) 84 microM, Km (glutamine) 7.0 mM, kcat 0.25 s(-1), and pH
      optimum 8.0. The enzyme was competitively, though non-cooperatively, inhibited by
      tryptophan.

PMID- 15235941
TI  - Involvement of histone hypoacetylation in Ni2+-induced bcl- 2 down-regulation and
      human hepatoma cell apoptosis.
AB  - Although induction of cell apoptosis is known to be involved in the cytotoxicity
      of Ni(2+), little research has been aimed at the mechanism of Ni(2+)-induced
      apoptosis. Recent studies showed that Ni(2+) induces histone hypoacetylation in
      different cell lines. Since histone hypoacetylation plays important roles in the
      control of cell cycle progress and apoptosis, we hypothesized that histone
      hypoacetylation may be an unrevealed pathway in Ni(2+)-induced apoptosis. To
      address this, effects of Ni(2+) on cell apoptosis, bcl- 2 gene expression and
      histone acetylation were examined in human hepatoma Hep3B cells. We found that
      Ni(2+) treatment resulted in cell proliferation arrest, the appearance of
      detached cells, condensed chromatin, apoptotic bodies and specific DNA
      fragmentation, indicating the occurrence of cell apoptosis. At the same time,
      Ni(2+) induced a significant decrease in bcl- 2 expression and histone
      acetylation; the decrease of histone H4 acetylation in nucleosomes associated
      with the bcl- 2 promoter region was also proven by a chromatin
      immunoprecipitation assay, indicating the involvement of histone hypoacetylation
      in Ni(2+)-induced bcl- 2 down-regulation. Further studies showed that increasing
      histone acetylation by either 100 nM of trichostatin A or over-expressing histone
      acetyltranferase p300 in Hep3B cells obviously attenuated the bcl- 2 down
      regulation and cell apoptosis caused by Ni(2+). Considering the importance of bcl
      2 in determining cell survival and apoptosis, the data presented here suggest
      that histone hypoacetylation may represent one unrevealed pathway in Ni(2+)
      induced cell apoptosis, where bcl- 2 is one of its targets.

PMID- 15235942
TI  - Effects of axial methionine coordination on the in-plane asymmetry of the heme
      electronic structure of cytochrome c.
AB  - The paramagnetic susceptibility ( chi) tensors of the oxidized forms of
      thermophile Hydrogenobacter thermophilus cytochrome c(552) (Ht cyt c(552)) and a
      quintuple mutant (F7A/V13 M/F34Y/E43Y/V78I; qm) of mesophile Pseudomonas
      aeruginosa cytochrome c(551) (Pa cyt c(551)) have been determined on the basis of
      the redox-dependent (1)H NMR shift changes of the main-chain NH and C(alpha)H
      proton resonances of non-coordinated amino acid residues and the NMR structures
      of the reduced forms of the corresponding proteins (J. Hasegawa, T. Yoshida, T.
      Yamazaki, Y. Sambongi, Y. Yu, Y. Igarashi, T. Kodama, K. Yamazaki, Y. Kyogoku, Y.
      Kobayashi (1998) Biochemistry 37:9641-9649; J. Hasegawa, S. Uchiyama, Y.
      Tanimoto, M. Mizutani, Y. Kobayashi, Y. Sambongi,Y. Igarashi (2000) J Biol Chem
      275:37824-37828). From the chi tensors determined, we obtained the contact shifts
      for heme methyl proton resonances, which provided the heme electronic structures
      of the oxidized forms of Ht cyt c(552) and qm. We also characterized the heme
      electronic structure of the cyanide adducts of the proteins, where the axial Met
      was replaced by an exogenous cyanide ion, through the analysis of (1)H NMR
      spectra. The results indicated that the heme electronic structures of both the
      proteins in their oxidized forms with axial His and Met coordination are largely
      different to each other, while those in their cyanide adducts are similar to each
      other. These results demonstrated that the orientation of the axial Met sulfur
      lone pair, with respect to heme, predominantly contributes to the spin
      delocalization into the porphyrin-pi system of heme in the oxidized proteins with
      axial His and Met coordination.

PMID- 15235943
TI  - Aprotinin and major orthopedic surgery.
AB  - Aprotinin is a potent pharmacological agent that reduces bleeding and limits
      blood transfusion requirements in current surgical practice. Many studies have
      been conducted in orthopedic surgery. In several trials performed in total hip
      replacement (THR) and total knee replacement (TKN) patients, aprotinin only
      moderately decreased blood-loss-replacement requirements. Conversely, when
      aprotinin was used in patients at high risk for bleeding (cancer, sepsis, redone
      surgery), it developed a potent hemostatic activity and decreased blood
      transfusion significantly. No increase in deep vein thrombosis and pulmonary
      embolism was observed. The only major side effect could be the potential
      occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin
      should be considered in extensive spine surgery and in high-risk major orthopedic
      operations. The decision to use aprotinin should be guided by a risk/benefit
      analysis.

PMID- 15235944
TI  - Effects of sevoflurane and enflurane on lower esophageal sphincter pressure and
      gastroesophageal pressure gradient in children.
AB  - PURPOSE: The effects of sevoflurane and enflurane on the intraluminal pressure of
      the lower esophagus (LE), lower esophageal sphincter (LES), and stomach were
      investigated in paralyzed and mechanically ventilated children under general
      anesthesia. METHODS: A total of 14 children, ASA physical status class I without
      risk factors for regurgitation, scheduled for orthopedic surgery were studied.
      After induction of anesthesia, we inserted a gastrointestinal pressure sensor
      nasally and monitored the intraluminal pressure of the LE, LES, and stomach under
      various concentrations of sevoflurane or enflurane with 66% nitrous oxide in
      oxygen prior to surgical incision. The barrier pressure (BrP), which is the
      difference between LES pressure and intragastric pressure, was calculated.
      RESULTS: Sevoflurane at 2.0 and 2.5 minimum alveolar concentration (MAC)
      decreased LES pressure, and enflurane at 2.0 and 2.5 MAC decreased both LES
      pressure and BrP in anesthetized children. The intraluminal pressure of the LE
      and stomach were not altered in either group. CONCLUSION: Sevoflurane and
      enflurane have an inhibitory effect on LES smooth muscle in anesthetized
      children. However, since the reduction was relatively low, even at high
      concentrations, these inhalation anesthetics are unlikely to influence
      gastroesophageal reflux during anesthesia.

PMID- 15235945
TI  - Preoperative aspirin and heparin therapy does not increase perioperative blood
      loss and blood product requirements in coronary artery bypass graft surgery.
AB  - PURPOSE: The effects of preoperative aspirin (ASA) and/or heparin therapy on
      perioperative blood loss and transfusion requirements were studied in patients
      undergoing primary coronary artery bypass graft (CABG) surgery using
      perioperative blood cell salvaging techniques. METHODS: The amounts of
      perioperative blood loss and transfusion requirements were recorded in four
      groups of patients, based on the preoperative medication: ASA group (51
      patients), heparin group (33 patients), and ASA plus heparin group (38 patients),
      as well as a control group (49 patients who received neither of these
      medications). RESULTS: There were no significant differences among the four
      groups in cardiopulmonary bypass time, aortic cross clamp time, or the number of
      coronary artery grafts performed. Postoperative blood loss was highest in the ASA
      group, followed by the control, the ASA + heparin, and the heparin groups.
      Neither postoperative blood loss nor transfusion requirements showed significant
      differences among the four groups. Simultaneous administration of heparin with
      ASA also did not increase the blood loss or transfusion requirements. CONCLUSION:
      Preoperatively administered aspirin and/or heparin did not significantly increase
      perioperative blood loss or the total amount of transfusion requirements. It is
      not necessary to delay elective CABG if blood cell salvaging techniques are used.

PMID- 15235946
TI  - Effect of lidocaine on pain caused by injection of propofol: comparison of three
      methods at two injection rates.

PMID- 15235947
TI  - No psychological emergence reactions in schizophrenic surgical patients
      immediately after propofol, fentanyl, and ketamine intravenous anesthesia.
AB  - PURPOSE: We attempted to determine the frequency of adverse psychological events
      after total intravenous anesthesia with propofol-fentanyl-ketamine (PFK) in
      surgical schizophrenic patients. METHODS: PFK was used in 25 schizophrenic
      patients undergoing various surgical procedures from 1995 to 1997. Adverse events
      occurring during and after anesthesia were recorded. Psychiatric follow-up was
      also done during the first 3 postoperative weeks at least. RESULTS: One patient
      died postoperatively of airway obstruction from concomitant severe malignant
      thyroid disease, but in the remaining patients neither respiratory nor
      cardiovascular states during or after anesthesia became unstable. None of the
      patients developed adverse psychological emergence reactions immediately after
      anesthesia. Two patients undergoing major surgical procedures exhibited delirium
      in the early postoperative days despite taking their routine antipsychotic drugs
      postoperatively. CONCLUSIONS: We suggest that PFK maintains stable respiratory
      and cardiovascular states, and causes no psychological emergence reactions in
      schizophrenic surgical patients. However, adverse psychological events may occur
      postoperatively, probably due to continued psychic stress. We therefore recommend
      appropriate perioperative management and further psychological studies for such
      patients.

PMID- 15235948
TI  - Effects of melatonin and superoxide dismutase on free radical formation in the
      postischemic reperfused heart.
AB  - PURPOSE: Melatonin has been reported to protect against oxygen free radicals. We
      investigated whether melatonin or superoxide dismutase (SOD) would decrease
      hydroxyl radical concentration in the postischemic reperfused heart. METHODS: An
      isolated rat heart-lung preparation was used. Eighty-one male Wistar rats were
      allocated into control (no drug), S1 (SOD 400 U.ml(-1)), S2 (SOD 2000 U.ml(-1)),
      M1 (melatonin 0.1 microg.ml(-1)), M2 (melatonin 1.0 microg.ml(-1)), M3 (melatonin
      10 microg.ml(-1)), SM (SOD 400 U.ml(-1) and melatonin 1.0 microg.ml(-1)) groups.
      The heart was perfused initially at the cardiac output of 30 ml.min(-1) and the
      mean arterial pressure of 70 mmHg. Drugs were administered into the reservoir 7
      min after the start of perfusion. Ten minutes after the start of perfusion, the
      heart was rendered globally ischemic for 10 min by reducing the preload and
      afterload to zero and then reperfused for 10 min. At the end of reperfusion, the
      heart was freeze-dried for 6 days. The perfusate blood was collected just before
      and after ischemia and at the end of reperfusion. The formation of hydroxyl
      radicals in perfusate blood and heart was measured with high-performance liquid
      chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid,
      yielding 2,3-, 2,4-, 2,5-, and 3,4-dihydroxybenzoic acid (DHBA). RESULTS: Before
      and after ischemia, there were no significant differences among the groups in
      cardiac output, systolic pressure, heart rate, and right atrial pressure. The
      concentrations of DHBAs in the perfusate blood and heart after ischemia and
      reperfusion in all groups were significantly higher than those before ischemia.
      DHBAs in the heart of all drug-administered groups were significantly lower than
      those in the control group. In the perfusate blood, DHBAs in the S2 group were
      significantly lower than those in the control group. CONCLUSIONS: SOD and
      melatonin decrease hydroxyl radical concentration in the postischemic reperfused
      heart.

PMID- 15235949
TI  - Effects of diadenosine tetraphosphate on systemic and regional hemodynamics in
      dogs.
AB  - PURPOSE: Diadenosine tetraphosphate (AP(4)A) produces vasodilation and
      hypotension. If AP(4)A is to be employed clinically, its influence on systemic
      and regional hemodynamics needs to be investigated. In this study, we observed
      systemic and regional hemodynamics during reduction of mean arterial pressure
      (MAP) induced by AP(4)A in dogs. METHODS: Nineteen mongrel dogs were allocated to
      three groups: those given physiological saline (vehicle group) and dogs in which
      MAP was decreased either by 8% (8% group) or by 30% (30% group) by infusion of
      AP(4)A. Systemic hemodynamics and microsphere-determined regional blood flow to
      vital organs were assessed before and during AP(4)A infusion. RESULTS: In the 8%
      group, cardiac output (CO) increased, and systemic vascular resistance (SVR)
      decreased during AP(4)A infusion. Although regional blood flow to myocardium and
      portal organs increased, hepatic blood flow decreased. In the 30% group, heart
      rate and SVR decreased, and stroke volume index increased without change in CO.
      Regional blood flow to myocardium, kidneys, and portal organs increased. In both
      groups, cerebral blood flow remained unchanged. CONCLUSION: During the decrease
      in MAP induced by AP(4)A, there were increases in regional blood flow distributed
      to the myocardium, kidneys, and portal organs, without change in the blood supply
      to the brain. This finding suggests that AP(4)A may be clinically useful for
      reducing blood pressure without compromising blood flow to vital organs.

PMID- 15235950
TI  - Cardiac effects of propofol and its interaction with autonomic nervous system in
      isolated, cross-circulated canine atria.
AB  - PURPOSE: The effects of propofol on sinoatrial pacemaker activity and myocardial
      contractility and its interaction with the autonomic nervous system were
      investigated in isolated, cross-circulated right atrial canine preparations.
      METHODS: An isolated right atrial preparation was perfused with heparinized
      arterial blood from an anesthetized support dog and changes in atrial rate and
      atrial contractile force were recorded. RESULTS: Propofol (30-1000 microg) and
      thiopental (30-1000 microg), injected into the sinus node artery of the isolated
      atrium, induced dose-dependent decreases in atrial rate and contractile force.
      The negative chronotropic and inotropic effects of propofol were greater than
      those of thiopental. The propofol-induced negative chronotropic and inotropic
      responses were not inhibited by atropine. Propofol had no effects on the cardiac
      responses to acetylcholine, norepinephrine, and the intracardiac parasympathetic
      nerve stimulation which activates ganglionic nicotinic acetylcholine receptors.
      CONCLUSION: These results indicate that: (a) propofol directly depresses
      sinoatrial pacemaker activity and myocardial contractility, (b) the negative
      chronotropic and inotropic effects of propofol do not involve activation of
      muscarinic receptors, and (c) propofol has little interaction with the autonomic
      nervous system at the effector site.

PMID- 15235951
TI  - Jugular venous oxygen saturation (Sjo2) monitoring in a patient with fulminant
      hepatic failure.

PMID- 15235952
TI  - A hemodynamic evaluation of propofol/fentanyl compared with isoflurane/fentanyl
      anesthesia in coronary artery bypass grafting.

PMID- 15235953
TI  - Reduction of regional cerebral oxygen saturation coincidental with a
      perioperative focal motor seizure.

PMID- 15235954
TI  - Changes in pain intensity of post-herpetic neuralgia following intravenous
      injections of ketamine hydrochloride.

PMID- 15235955
TI  - Postoperative hypoxemia following sequential resection of bilateral pulmonary
      lesions by median sternotomy.

PMID- 15235956
TI  - Abnormal rigidities of the muscles and joints of the lower limb induced by a
      short-term, low-pressure tourniquet.

PMID- 15235957
TI  - Does halothane or sevoflurane inhibit NO-stimulated soluble guanylyl cyclase
      activity under physiological conditions?

PMID- 15235959
TI  - The echocardiographic assessment of left ventricular performance during
      sevoflurane and halothane anesthesia.
AB  - The cardiovascular effects of sevoflurane were studied and compared with those of
      halothane in 30 healthy patients. The patients were assigned to receive 1 MAC
      sevoflurane (n = 10), 2 MAC sevoflurane (n = 10) or 1 MAC halothane (n = 10) in
      N(2)O 2 l.min(-1) and O(2) 4 l.min(-1). The changes in left ventricular diastolic
      and systolic dimension (Dd and Ds), fractional shortening (FS), mean velocity of
      circumferential fiber shortening (mVcf), left ventricular diastolic and systolic
      volume (Vd and Vs), stroke volume (SV), ejection fraction (EF) and cardiac index
      (CI) were evaluated by echocardiography. Sevoflurane produced significant dose
      dependent decreases in FS, mVcf, EF and SV, but no significant changes in Dd and
      Vd. Therefore, the decrease in SV was due mainly to the increase in left
      ventricular residual volume (Vs). One MAC halothane produced a more significant
      decrease in FS, mVcf, EF and SV, when compared to values obtained at 1 MAC
      sevoflourane ( P < 0.01). CI was more significantly decreased with 1 MAC
      halothane than with 1 MAC and 2 MAC sevoflurane ( P < 0.01). This was brought
      about by a slight decrease in HR with halothane and a slight increase in HR with
      sevoflurane, in addition to a smaller decrease in SV with sevoflurane than with
      halothane. This study suggests that sevoflurane may better preserve cardiac
      function as a pump in healthy patients, when compared to halothane.

PMID- 15235960
TI  - The antiarrhythmic effect of flecainide on halothane-epinephrine induced
      arrhythmias in dogs.
AB  - The antiarrhythmic effect of flecainide acetate (FCN), a newly developed class I
      antiarrhythmic drug, was evaluated on epinephrine (E)-halothane induced
      arrhythmias in dogs. The arrhythmogenic dose of E (ADE) under 1% of halothane was
      significantly increased from 0.71 +/- 0.08 to 1.08 +/- 0.11 and 1.84 +/- 0.23
      micro g.kg(-1).min(-1) by the administration of 2 and 4 mg.kg(-1) of FCN,
      respectively. The arrhythmias induced by ADE in the absence of FCN were stopped
      by 1.78 +/- 0.29 mg.kg(-1) of FCN in bolus injections. These results suggest that
      FCN can be used for the treatment of arrhythmias that E contributes to under
      halothane anesthesia.

PMID- 15235961
TI  - Cyclic alteration in the anticonvulsant effect of nitrous oxide in rats.
AB  - The anticonvulsant action of nitrous oxide and its time course were studied in
      rats. Bicuculline, a GABA-receptor antagonist, was administered intravenously at
      a rate of 0.2 mg.kg(-1).min(-1) during exposure to air (n = 60) or 75% nitrous
      oxide in oxygen (n = 80). The convulsant dose of bicuculline was determined. The
      rats were divided into subgroups according to the duration of exposure to air or
      nitrous oxide, from 0 to 120 min at 15 min intervals. Although the convulsant
      dose of bicuculline was consistent in the air group (1.03 +/- 0.06 mg.kg(-1),
      mean +/- SEM), it showed two peaks at 30- and 90 min exposures to nitrous oxide.
      The threshold dose in the nitrous oxide group was significantly higher than in
      the air group at only 15- and 30 min exposures (1.50 +/- 0.16, 2.15 +/- 0.25
      mg.kg(-1), respectively, P < 0.05). We conclude that nitrous oxide has an
      anticonvulsant action against bicuculline-induced seizure, and that a cyclic
      nature exists in its action.

PMID- 15235962
TI  - Oxygen delivery and consumption in the perioperative period of coronary artery
      bypass grafting without blood transfusion.
AB  - The perioperative changes in relationship between oxygen delivery (D(O)(2)) and
      oxygen consumption (V(O)(2)) were examined in forty patients who underwent
      coronary artery bypass grafting (CABG) without blood transfusion. Hemodilution
      was performed to maintain hematocrit of 19.2 +/- 1.8% during cardiopulmonary
      bypass (CPB). Hemodynamic and metabolic parameters were measured in four stages;
      before CPB (stage I), after CPB (stage II), after ICU arrival (stage III), and
      the following day (stage IV). In each stage, there was a strong positive
      correlation between V(O)(2) and D(O)(2). In stage I, a decrease in D(O)(2) was
      met with low V(O)(2), and there was no imbalance between them (r = 0.67, P <
      0.01). V(O)(2) increased significantly in stage II, and this increased V(O)(2)
      was compensated by an increase in D(O)(2) sufficiently to meet tissue oxygen
      demand (r = 0.59, P < 0.01). In stage III and IV, the increases in tissue oxygen
      requirements were met by increases in oxygen extraction ratio (r = 0.81, P <
      0.01, r = 0.60, P < 0.01, respectively) reflected in lowered mixed venous oxygen
      tension and saturation. From these results, it is assumed that the adequate
      relationship between V(O)(2) and D(O)(2) can be maintained in the perioperative
      period of CABG without blood transfusion.

PMID- 15235963
TI  - Changes in pulmonary function during continuous epidural bupivacaine with or
      without morphine following upper abdominal surgery.
AB  - To assess the effect of postoperative continuous thoracic epidural infusion of
      bupivacaine on pulmonary function, a prospective randomized study was conducted
      in patients undergoing upper abdominal surgery (UAS). Sixteen patients, divided
      into two treatment groups, received continuous epidural infusion of 0.25%
      bupivacaine at a rate of 2-5 ml.hr(-1), or that of a combination of 0.125% or
      0.25% bupivacaine and 0.0025% or 0.005% morphine at a rate of 2-4 ml.hr(-1). One,
      4, 10, 16, 24 and 40 hr postoperatively, the following indices were measured:
      visual analogue scale score, modified Prince Henry pain scale score, arterial
      Pa(O)(2) and Pa(CO)(2), functional residual capacity (FRC), and tidal volume
      (TV). There was no difference in pain scores between the two groups except for
      significantly less pain at 40 hr in the combination group. Postoperative
      measurements of pulmonary function revealed a significant fall in Pa(O)(2), FRC
      and TV, indicating a reduction of 15-25% as compared with the preoperative
      values, and no significant differences between the two groups. The authors
      conclude that postoperative continuous epidural infusion of bupivacaine combined
      with morphine is highly effective in alleviating pain and improving pulmonary
      function in patients following USA.

PMID- 15235964
TI  - Concentration- and pH-dependent effects of local anesthetics on onset of epidural
      anesthesia.
AB  - This study was undertaken to determine the effect of concentration of pH-adjusted
      local anesthetics on the onset time of anesthesia.Lidocaine (0.9% and 1.8%) and
      bupivacaine (0.25% and 0.5%) were used. In the 0.9 percent lidocaine and 0.25
      percent bupivacaine groups, the onset time of analgesia was shortened by about
      100 and 200 seconds, when pH was adjusted to 7.4 and 7.0, respectively ( P < 0.05
      and P < 0.01). In the 1.8 percent lidocaine and 0.5 percent bupivacaine groups,
      however, pH adjustment exerted no significant effect on the onset time.
      Alkalinization of low-concentration local anesthetics shortened the onset time,
      whereas that of high-concentration did not shorten.

PMID- 15235965
TI  - Effects of intravenous or endotracheal lidocaine on circulatory changes during
      recovery from general anesthesia.
AB  - Intravenous lidocaine (1.5 mg.kg(-1)) was not effective in attenuating the
      circulatory changes and the cough reflex induced by airway stimulation during
      recovery from general anesthesia, whereas endotracheal 4% lidocaine (3 ml) was
      effective. The arterial concentration of the intravenously administered-lidocaine
      peaked at a level of 9.52 +/- 0.81 microg.ml(-1) 0.5 min later. The arterial
      concentration of the endotracheally administered-lidocaine peaked at 1.44 +/-
      0.13 microg.ml(-1) 15 min later. These findings indicate that the endotracheal
      administration of lidocaine may be superior to the intravenous administration for
      attenuating the circulatory changes and the cough reflex during recovery from
      general anesthesia, and that the arterial concentration of lidocaine did not
      correlate with the clinical efficacy for this purpose.

PMID- 15235966
TI  - The effects of nicardipine given after 10-minutes complete global cerebral
      ischemia on neurologic recovery in dogs.
AB  - The effect of nicardipine (NC) on neurologic recovery from ischemic insult after
      10-minutes complete global cerebral ischemia was evaluated in dogs by examination
      of neurologic recovery score (NRS: complete recovery = 100, death = 0). Ischemia
      was achieved by occlusion of ascending aorta, and NC, 10 microg.kg(-1) in bolus
      followed by infusion of 0.33 microg.kg(-1).min(-1) for 2 hours, was administered
      immediately after re-establishment of circulation. The mortality at 7th day was
      2/9 in the control Copyright and 1/9 in the NC group (ns). NRS on 2nd day was
      52.3 +/- 6.8 in the C and 70.6 +/- 6.5 in the NC ( P < 0.05), but that on 7th day
      did not differ between the two groups. The numbers of dogs recovered to over 80
      in NRS on the 2nd day was 1/9 in the C and 5/9 in the NC ( P < 0.05), but that on
      the 7th day increased to 3/9 in the C and remained at 5/9 in the NC (ns). These
      results suggest that NC accelerates the early neurologic recovery from ischemic
      damage, but influences little the final outcome.

PMID- 15235967
TI  - Breathing pattern and respiratory mechanics in sevoflurane-anesthetized humans.
AB  - In order to determine the respiratory effects of sevoflurane in humans, breathing
      pattern and mechanical behavior of respiratory system were investigated in ten
      subjects at anesthetic depth of 1 MAC (minimum alveolar concentration). Average
      tidal volume and breathing frequency amounted to 275 ml and 20.9 breaths per
      minute. Arterial carbon dioxide tension amounted to 45.6 mmHg. Duration of
      inspiration was 1.06s and that of expiration was 1.92s. Mean inspiratory flow
      rate amounted to 259 ml.s(-1). Average value of passive respiratory elastance
      determined by the method of Zin et al. amounted to 21.8 cmH(2)O. l(-1), while
      those of active respiratory elastance and resistance obtained by the method of
      Behrakis et al. were 28.0 cmH(2)O. l(-1) and 3.15 cmH(2)O. l(-1).s(-1),
      respectively. Values of these variables were compared to those reported in
      halothane and enflurane anesthesia and possible explanations of the differences
      between the anesthetics are discussed.

PMID- 15235968
TI  - Characteristic changes between core and peripheral surface temperature related
      with postanesthetic shivering following surgical operations.
AB  - The relationship between changes in the core and the surface temperature and
      postanesthetic shivering was studied in 100 patients who underwent general
      anesthesia. Patients were classified into four groups by the patterns of change
      in the core and peripheral surface temperature. Type II and type IV groups of
      patients showed a decrease in surface temperature during the major operation such
      as gastrectomy and radical mastectomy. Type I and type III groups of patients
      showed no lowered peripheral surface temperature and with low temperature
      difference between core and surface temperature during the operation. The
      patients in type II and IV groups showed increased difference between core and
      surface temperature. The postanesthetic shivering occurred at significantly
      higher rate compared to the other two groups. As possible reasons of the
      shivering, operation of long duration and insufficient circulating blood volume
      were considered. Shivering reduces the temperature difference in the
      thermoregulatory homeostasis. However, in patients in type I and III, the rate of
      shivering was low. Evaluation of the difference between core and peripheral
      surface temperature may be important to manage body temperature at a steady level
      during the operation. The monitoring of body temperature difference between core
      and peripheral surface during the operation may be useful for predicting to
      occurrence of postanesthetic shivering.

PMID- 15235969
TI  - Perioperative management of a neonatal aneurysm of the vein Galen with heart
      failure.

PMID- 15235970
TI  - Anesthesia for acute pulmonary embolism.

PMID- 15235971
TI  - Malfunction of infusion pump due to electrosurgical unit interference.

PMID- 15235972
TI  - Perioperative management of a patient with congenital afibrinogenemia.

PMID- 15235973
TI  - Spontaneous remission of epidural hematoma following continuous epidural
      anesthesia.

PMID- 15235974
TI  - The effects of prolonged controlled hypotension induced by prostaglandin E1 on
      renal tubular function.
AB  - The effects of the prolonged 3-hour and 6-hour controlled hypotension induced by
      prostaglandin E(1) (PGE(1)) on renal tubular function have been comparatively
      studied with trimethaphan (TMP; 3-hour hypotensive anesthesia) and enflurane deep
      anesthesia (6-hour hypotensive anesthesia), using the urine N-acetyl-Beta-D
      glucosaminidase (NAG index) and the serum and urine Beta(2)-microglobulin
      (fractional clearance of Beta(2)-m; Fc-Beta(2)-m) as markers. During 3-hour and 6
      hour controlled hypotension PGE(1), NAG index and Fc-Beta(2)-m and urine volume
      could be maintained without remarkable changes. In the group with TPM, NAG index
      and Fc-Beta(2)-m significantly increased. The increasing trend was also noted
      over time in deep anesthesia with enflurane. On 1st postoperative day, Fc-Beta(2)
      m significantly increased in PGE(1) group in both 3-hour and 6-hour hypotensive
      anesthesia, whereas it restored to normal on 2nd postoperative day. Also, in TMP
      and enflurane deep anesthesia, Fc-Beta(2)-m significantly increased on 1st
      postoperative day. With the latter, significant increase was also observed on 2nd
      postoperative day. These results suggest that, in 3-hour and 6-hour controlled
      hypotension induced by PGE(1), renal tubular function is normally maintained and
      that it is useful for prolonged controlled hypotensive anesthesia. However,
      further study is necessary because tubular dysfunction might appear on 1st
      postoperative day.

PMID- 15235975
TI  - Tracheobronchial dilating effect of high frequency jet ventilation.
AB  - Effect of high frequency jet ventilation (HJFV) on tracheobronchial tone was
      examined in anesthetized dogs. Changes in intraluminal pressure of water-filled
      endotracheal cuff (Pcuff) were used as an indicator of tracheal smooth muscle
      tone. Animals were initially ventilated with conventional mechanical ventilation
      (CMV) to maintain normal Pa(CO)(2). HFJV (2.0 Hz.) was then applied to each
      animal in such a way to maintain the same mean airway pressure and Pa(CO)(2) as
      in CMV. Immediately after changing CMV to HFJV, Pcuff decreased significantly and
      remained decreased during the period of HFJV. After changing HFJV to CMV, Pcuff
      gradually returned to its previous level. Histamine-induced tracheobronchial
      constriction was partially released by HFJV as shown by a decrease in Pcuff and
      airway resistance (Raw) and by an increase in static lung-thorax compliance (Cst)
      measured immediately after the cessation of HFJV. These results suggest that HFJV
      has a tracheobronchial dilating action, presumably mediated by pulmonary stretch
      reflex, and this may be one of the mechanisms of an increase in mucous secretion
      and of other reported favorable effects of HFJV in some types of respiratory
      failure.

PMID- 15235976
TI  - Evaluation of conventional weaning criteria in patients with acute respiratory
      failure.
AB  - We evaluated the reliability of conventional weaning criteria from a ventilator
      during 33 weaning trials on 25 patients with acute respiratory failure (ARF). Of
      13 criteria, a ratio of maximal voluntary ventilation to minute ventilation (MV)
      >2, a vital capacity >12 ml.kg(-1), a spontaneous respiratory rate <25
      breaths.min(-1), and a MV <10 l.min(-1) appeared to be useful for predicting
      successful weaning outcome. However, even using those criteria, there were many
      falsely-negative cases. The alveolar-arterial P(O)(2) gradient <350 mmHg at an F
      i(O)(2) 1.0 was not useful as a predictor of weaning outcome. The present study
      demonstrates that conventional criteria are frequently inaccurate for predicting
      weaning outcomes and suggests that the use of some of these criteria may
      unnecessarily prolong the length of ventilator support. Since ventilation of most
      patients with poor oxygenation can be successfully discontinued by placing them
      on a continuous positive airway pressure system, these results suggest that the
      improvement of oxygenation is not an indispensable prerequisite for weaning from
      mechanical ventilators.

PMID- 15235977
TI  - Continuous epidural infusion for postoperative mechanical ventilation.
AB  - We evaluated in analgesic and sedative effects of continuous epidural infusion of
      two analgesic regimens in ventilated patients following esophagectomy. Forty-six
      patients, divided into two treatment groups, received postoperative continuous
      epidural infusion of morphine, or that of a combination of bupivacaine and
      morphine. Assessments were made with the following indices: pain relief score,
      somnolence score, patient ventilator coordination score, and the number of
      supplemental administrations of analgesics and sedatives. No significant
      differences occurred in somnolence scores or patient ventilator coordination
      scores between the two groups, which revealed satisfactory sedation for
      mechanical ventilation. Patients receiving the combination of bupivacaine and
      morphine had significantly less pain postoperatively, requiring a smaller number
      of supplemental administrations of analgesics and sedatives ( P < 0.05). It is
      concluded that: 1) continuous epidural infusion of analgesics gives potent
      analgesia and sedation of ventilated patients following esophagectomy; 2) the
      combination of bupivacaine and morphine gives pain relief superior to morphine
      alone.

PMID- 15235978
TI  - Enflurane impairs canine diaphragmatic contractility in vivo.
AB  - We examined the effect of enflurane on diaphragmatic contractility in six
      anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed
      from transdiaphragmatic pressure (Pdi) developed at functional residual capacity
      against an occluded airway during cervical phrenic nerve stimulation. Pdi
      stimulus frequency relationship was compared at three levels of anesthesia,
      namely 1, 1.5, and 2 MAC (minimum alveolar concentration) of enflurane. The
      sequence of changing anesthetic concentration was randomized between animals. Pdi
      at 50 and 100 Hz stimulation was significantly decreased with increasing MAC
      while Pdi at 10 Hz stimulation was not affected by the depth of anesthesia. Pdi
      of 20 Hz stimulation was significantly decreased at 2 MAC as compared to those at
      1 and 1.5 MAC. We conclude that enflurane decreases contractility of the
      diaphragm mainly through impairment of the neuromuscular transmission and/or
      membrane excitability. Part of its effects is, however, probably related to the
      impairment of excitation-contraction coupling, as suggested by the depression of
      Pdi at 2 MAC in response to 20 Hz stimulation.

PMID- 15235979
TI  - Hemodynamic effects of high-frequency jet ventilation in dogs with acute right
      coronary arterial ligation and pulmonary arterial banding.
AB  - The hemodynamic effects of high-frequency jet ventilation (HFJV), synchronized
      with diastole, and intermittent positive-pressure ventilation (IPPV) were studied
      in 10 dogs with acute right-sided myocardial ischemia and elevated right
      ventricular pressure. Myocardial ischemia was produced by ligation of the
      proximal right coronary artery (RCA), then the right ventricular pressure was
      elevated to facilitate the ischemia by banding the main pulmonary artery. Before
      and 1, 2, 3, and 5 hr after the RCA ligation, cardiorespiratory variables for
      each ventilatory mode and creatine phosphokinase MB isoenzyme (CPK-MB) were
      measured. During HFJV compared with IPPV: there were significant increases in
      stroke index and left ventricular stroke work index at all ischemic periods, and
      decreases in peak and mean airway pressures and pulmonary vascular resistance at
      all ischemic periods, and in the product of systolic right ventricular pressure
      and heart rate at 2 hr, 3 hr, and 5 hr. The difference in mean airway pressure
      between IPPV and HFJV correlated significantly with those in cardiac index and
      stroke index (r = 0.575 and 0.779, respectively). CPK-MB was significantly
      greater at 3 hr and 5 hr than that before RCA ligation. These findings suggest
      that HFJV synchronized with diastole offers hemodynamic advantages over IPPV to
      ischemic right ventricle with constricted pulmonary artery, mainly due to
      lowering the mean airway pressure.

PMID- 15235980
TI  - Comparison of anesthetic effects of epidural and intravenous administration of
      buprenorphine during operation.
AB  - Thirty six patients were received epidural anesthesia with or without
      buprenorphine (BPN) during upper abdominal surgery. They were divided into three
      groups of 12 patients as follows; G-I received 20 ml of 1% lidocaine epidurally,
      G-II received 20 ml of 1% lidocaine epidurally and 0.6 mg BPN intravenously, G
      III received 20 ml of 1% lidocaine with 0.6 mg BPN epidurally. Additional 5 ml of
      1% lidocaine was given to any patient if systolic blood pressure or heart rate
      increased 10% compared to control value. Trachea was intubated following
      anesthetic induction with thiopental. The lungs were ventilated with a mixture of
      N(2)O/O(2) (33%) and pancuronium was used for muscle relaxation. The total
      required doses of lidocaine in G-II and G-III were decreased 60% compared to
      control group (G-I) ( P < 0.05). The mean period of time until the first
      administration of pentazocine for postoperative pain was 13 +/- 10 hr (mean +/-
      SD) in G-II and 19 +/- 24 hr in G-III compared to 5 +/- 4 hr in G-I ( P <<
      0.001). The dose of the administration of pentazocine that was required for pain
      relief during the first 48 postoperative hr in G-III was 54 +/- 10 mg (mean +/-
      SD) compared to 150 +/- 21 mg in G-I ( P < 0.02) and 106 +/- 28 mg in G-II ( P <
      0.05). Recovery from anesthesia in G-III was more rapid than that in G-I ( P <
      0.05). The Pa(CO)(2) values in G-II and G-III increased 15% compared to control
      group at about 4 hr and 8 hr after administration of BPN, but any clinical
      treatment was not needed for them. Nonrespiratory side effects, e.g., nausea,
      vomiting, fatigue and headache, were comparably common in all groups. Mild
      hematuria associated with acute hypotension occurred in two patients in G-II
      (17%) immediately after the intravenous injection of 0.6 mg of BPN. The results
      showed that 0.6 mg of BPN given epidurally demonstrated better anesthetic and
      more potent postoperative analgesic effects and lesser side effects than 0.6 mg
      of BPN given intravenously in patients undergoing upper abdominal surgery.

PMID- 15235981
TI  - The degree of muscle relaxation requested by the surgens during upper abdominal
      surgery.
AB  - The degree of muscle relaxation required for the abdominal surgery should differ
      at different phase of operation. To test this hypothesis muscle relaxation was
      assessed subjectively by the surgeon and the results were compared with
      quantitative observations of the degree of response depression to train of four
      (t4) stimulation at various stages of surgery. Maximum relaxation, with a t4
      ratio of less than 10%, was required immediately after the skin incision and
      during closure of the abdominal wall, while the requirement was minimal during
      the major part of surgery when the intra-abdominal procedures were performed.

PMID- 15235982
TI  - Noninvasive assessment of cardiac performance of intravenous benzodiazepines by
      systolic time intervals.
AB  - The effects of anesthetic induction by diazepam, flunitrazepam and midazolam on
      cardiac performance were evaluated in 33 ASA class I surgical patients (average
      age was 36 years). The patients were divided according to the 3 drug groups, and
      the effects of each drug assessed utilizing measurements of systolic time
      intervals. An increase in heart rate and decrease in blood pressure was observed
      following flunitrazepam and midazolam induction. There was no changes in PEPI
      (pre-ejection period index) and LVETI (left ventricular ejection time index) by
      benzodiazepines induction. The PEP/LVET ratio was increased by diazepam while the
      DPTI (diastolic pressure time index)/TTI (tension time index) was reduced by
      flunitrazepam and midazolam. However, these changes in PEP/LVET and DPTI/TTI were
      within normal limits. These data indicate that in healthy humans the induction
      dose of either diazepam, flunitrazepam or midazolam does not extremely influence
      either PEP/LVET for cardiac performance or DPTI/TTI for cardiac oxygen balance.
      The results also suggest that the simultaneous use of PEP/LVET and DPTI/TTI is
      more informative than any single variable for the evaluation of cardiac effects
      of anesthetics.

PMID- 15235983
TI  - Changes in breathing patterns after lung operations.
AB  - To assess the effects of thoracic surgery on breathing patterns without conscious
      intervention, we analyzed and compared the breathing patterns observed
      immediately before and after surgical procedure while anesthesia was maintained
      with enflurane and nitrous oxide at a constant level in 15 patients undergoing
      thoracic surgery. Our results showed that immediately after the surgical
      procedure, respiratory frequency (f) was significantly higher and tidal volume
      (V(T)) was significantly smaller than those observed immediately before the
      surgical procedure. The increased f during the period immediately after the
      surgical procedure was due to shortening of both inspiratory time (T(I)) and
      expiratory time (T(E)) without changing the ratio of T(I) to the total breath
      time (T(tot)). Despite the significant decrease in V(T) observed immediately
      after the surgical procedure, the value of negative pressure during the occluded
      inspiration (P(max)) was significantly higher than that observed immediately
      before the surgical procedure. These results indicate that a rapid, shallow type
      of breathing pattern can occur after thoracic surgery without conscious
      intervention.

PMID- 15235984
TI  - Effects of midazolam on the threshold of lidocaine-induced seizures in the dog-
      comparison with diazepam.
AB  - The anticonvulsive effect of midazolam was compared with that of diazepam in ten
      dogs. Lidocaine-induced seizure waves on the electroencephalogram were used to
      observe the suppressive effect of the drugs. Midazolam, 0.2 mg.kg(-1), was found
      to possess a stronger suppressive effect against lidocaine-induced seizures than
      the same dose of diazepam. These two drugs showed to possess similar effects on
      cerebral and systemic circulations and cerebral metabolism during seizures.

PMID- 15235985
TI  - New lidocaine ester derivatives with a prolonged anesthetic effect.
AB  - In order to find a new long acting local anesthetic, methyl, ethyl, and butyl
      ester derivatives of lidocaine were synthesized in our laboratory. The topical
      anesthetic activity was studied with the effects on corneal reflex in rabbits,
      and the duration of action with those on the action potential of rabbit vagus
      nerve was studied in vitro. All drugs showed adequate topical anesthetic
      activities. The onset time to induce a complete blockage of the action potential
      in the excised vagus nerve was 97.1 +/- 6.3 s for lidocaine, 289.3 +/- 29.0 s for
      methyl ester, 186.3 +/- 18.4 s for ethyl ester, and 85.3 +/- 9.0 s for butyl
      ester. The mean duration of action, which was assessed as the time to recover
      from the complete block to 30% of control amplitude in a drug-free medium, was
      32.5 +/- 3.1 min for lidocaine, 39.9 +/- 11.3 min for methyl ester, 68.2 +/- 4.2
      min for ethyl ester, and 108.7 +/- 12.3 min for butyl ester. The differences in
      the duration of action between the ester derivatives and the original lidocaine
      were all statistically significant. The duration of action of all drugs studied
      paralleled with their protein binding capacities. These findings indicate the
      possibility that the ester derivatives studied, especially butyl ester, can be
      used as a long acting local anesthetic.

PMID- 15235986
TI  - Anesthesia for arthrogryposis multiplex congenita--report of 12 cases.

PMID- 15235987
TI  - The anesthetic management for emergency operation on a patient with dilated
      cardiomyopathy.

PMID- 15235988
TI  - Successful weaning from prolonged mechanical ventilation by embolization of aorta
      pulmonary collateral arteries.

PMID- 15235989
TI  - Total obstruction of the right main-stem bronchus displayed in changes of airway
      dynamics during differential ventilation with double-lumen tube intubation.

PMID- 15235990
TI  - Treatment of hypoxemia during esophagectomy by high frequency jet ventilation.

PMID- 15235991
TI  - No sensory block with spinal bupivacaine a case report.

PMID- 15235992
TI  - Airway occlusion pressure (P0.1)-a useful predictor for the weaning outcome in
      patients with acute respiratory failure-.
AB  - Twenty-five patients who required mechanical ventilatory support (MVS) after
      major surgery or severe burns were studied to determine whether airway occlusion
      pressure (P(0.1)) is a clinically useful indicator to predict the success or
      failure of the weaning trial. A total of 33 weaning trials were attempted on
      these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by
      failure. Although the success group, when compared with the failure group, had a
      lower respiratory rate ( P << 0.001), a lower minute ventilation ( P << 0.001), a
      higher maximal voluntary ventilation to minute ventilation ratio ( P << 0.01) and
      a higher forced vital capacity ( P << 0.05), no threshold values separated the
      success from the failure group. The alveolar-arterial P(O)(2) gradient, with an F
      i(O)(2) of 1.0, in weaning success and failure showed no statistical difference.
      In contrast, all patients in the success group had a P(0.1) of less than 3.5
      cmH(2)O and those in the failure group had a P(0.1) of greater than 3.5 cmH(2)O (
      P << 0.001). We conclude that P(0.1) is a clinically superior indicator for
      discontinuing MVS in patients with acute respiratory failure.

PMID- 15235993
TI  - Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal
      activity induced by BK injection in spinal cats.
AB  - The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition
      of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin
      (BK) injection was studied in spinal cats. Extracellular activity was recorded in
      the dorsal horn from single WDR neurons responding to noxious and non-noxious
      stimuli applied to the cutaneous receptive fields on the left hind paw foot pads
      of decerebrate, spinal cord transected (L(1-2)) cats. When 10 microg of BK was
      injected into the femoral artery ipsilateral to the recording site as the noxious
      test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%)
      gave inhibitory responses. On the other hand, when the injection of 10 microg of
      BK into the femoral artery contralateral to the recording site was used as the
      noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3
      (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory
      neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but
      was depressed significantly by 2.5%. However, the inhibitory neuronal activity in
      WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have
      found that enflurane reduces the excitation as well as the inhibition of dorsal
      horn WDR neuronal activity induced by BK injection. These results suggest that
      the reduction of excitatory and inhibitory responses produced by noxious
      stimulation is likely to be the fundamental basis of the enflurane-induced
      anesthetic state in terms of WDR neurons.

PMID- 15235994
TI  - The changes in brain surface, intracerebral tissue, and transconjunctival oxygen
      tension during hypo- and hyperventilation.
AB  - To evaluate the validity of organ surface oxygen tension monitoring for
      assessment of cerebral perfusion, the oxygen tension in brain surface
      (Pbs(O)(2)), intracerebral tissue (Pic(O)(2)), and conjunctiva (Pcj(O)(2)) were
      measured simultaneously during hypo- and hyperventilation in dogs, and the
      comparative study was done. Pbs(O)(2) and Pic(O)(2) significantly increased
      during hypoventilation and decreased during hyperventilation. And the values of
      Pbs(O)(2) and Pic(O)(2) were correlated to the corresponding Pa(CO)(2) values
      significantly ( P << 0.001 in each case). On the contrary, Pcj(O)(2) did not
      change significantly during hypo- and hyperventilation. These findings indicate
      that Pbs(O)(2) as well as Pic(O)(2) could reflect the changes in cerebral
      perfusion caused by induced hyper- and hypocapnia but that Pcj(O)(2) could not.

PMID- 15235995
TI  - Changes in brain monoamines and their metabolites during and after hemorrhagic
      shock in the rat.
AB  - The alteration of monoamines and their metabolites in the brain during and after
      hemorrhagic shock in the conscious state was measured in rats. Blood pressure was
      maintained at 40-70 mmHg (5.3-9.3 kPa) for 60 min by withdrawing 8 ml of blood
      intermittently. The content of monoamines, as well as their metabolites,
      increased in various brain regions during hemorrhage, compared with the content
      in the control rats. Sixty min after the end of the bleeding period, almost no
      significant change in the contents of brain monoamines nor of their metabolites
      was observed. These results may indicate not only an increased release of
      monoamines from nerve terminals, but also an increased synthesis of them during
      hemorrhagic shock. Soon after the bleeding was stopped, the increased monoamine
      turnover rate returned to almost normal levels.

PMID- 15235996
TI  - Sevoflurane has no inhibitory effect on hypoxic pulmonary vasoconstriction (HPV)
      in dogs.
AB  - There is no general agreement on the effect of inhalation anesthetics on hypoxic
      pulmonary vasoconstriction (HPV). We have examined the effect of sevoflurane upon
      the pulmonary vascular response to a left lower lobe (LLL) hypoxia in dogs by
      continuously measuring the fractional distribution to the LLL of total pulmonary
      blood flow (Q(LLL)/Q(T)) employing an ultrasonic transit time rheometer with flow
      probes attached to the LLL artery and the main pulmonary artery. During regional
      hypoxia without sevoflurane, blood flow distribution to the LLL as a mean was
      48.2% of that determined under hyperoxic conditions. When sevoflurane was
      administered at concentrations of 2% and 4%, the LLL blood flow distributions
      during hypoxia were as a mean 40.2% and 47.0%, respectively, of the values
      obtained during the first hyperoxic periods. No change occurred in the pulmonary
      vascular resistance of the LLL(PVR(LLL)) and the shunt ratio(Qs/Qt) between the
      concentrations used. Thus there was no significant effect of sevoflurane upon HPV
      whatever concentration used.

PMID- 15235997
TI  - The changes in arterial keton bodies during upper abdominal surgery.
AB  - The relationship between the arterial keton body ratio (AKBR: acetoacetate/Beta
      hydroxybutyrate) and the plasma hormone activities were studied under a general
      anesthesia using enflurane group (group G) and a GO + Epidural group (group E)
      with continuous glucose loading (10 g.hr(-1)) during partial gastrectomy. In both
      groups, the AKBR increased significantly during the operation. The plasma insulin
      activity was significantly positively correlated with the AKBR and it was
      negatively correlated with log (Beta-hydroxybutyrate) in both groups. We could
      not find any significant difference of the AKBR between group G and group E. Our
      results indicate that the plasma insulin activity affects the arterial keton body
      ratio and that the AKBR must be evaluated considering the plasma hormone
      activity, especially insulin activity during the operation.

PMID- 15235998
TI  - Continuous epidural infusion for postoperative pain relief: a comparison of three
      regimens.
AB  - We evaluated the postoperative pain relief and side-effects of continuous
      epidural infusion of three analgesic regimens following major thoracic and/or
      abdominal surgery. One hundred and twenty patients were randomly divided into
      three treatment groups: (1) 0.25% or 0.5% bupivacaine at a rate of 3-7 ml.hr(-1),
      (2) 0.01% morphine at a rate of 1-2 ml.hr(-1), (3) a combination of 0.125% or
      0.25% bupivacaine and 0.0025% or 0.005% morphine at a rate of 2-4 ml.hr(-1). The
      study continued for the first 48 postoperative hours. The effect of pain relief
      was evaluated by assessment of the further requirement for parenteral analgesics.
      Sixty-four percent of the patients given bupivacaine, 56% of the patients given
      morphine and 80% of the patients given the combination required no supplemental
      analgesics. Continuous epidural infusion of bupivacaine was associated with
      hypotension (21%) and with numbness and weakness of hands or legs (18%).
      Continuous epidural infusion of morphine was associated with pruritus (18%) and
      with peristaltic depression (12%). The combination regimen was associated with
      pruritus (17%) and with drowsiness (14%). We conclude that the combination of
      bupivacaine and morphine significantly provides superior analgesia with less
      deleterious complications compared with either bupivacaine or morphine alone.

PMID- 15235999
TI  - Effects of nitrous oxide on single breath induction with enflurane.
AB  - A single vital capacity breath method of inhalational induction using 4%
      enflurane in 67% nitrous oxide (group I) or 100% oxygen (group II) was studied in
      30 patients. Nitrous oxide accelerated induction time (71 (22 SD) seconds in
      group I versus 136 (29 SD) in group II, P </= 0.01) and was associated with a
      decreased incidence of excitement and respiratory disturbance ( P </= 0.05).
      There were no significant differences between groups in systolic blood pressure,
      heart rate or arterial oxygen saturation. The technique was acceptable to 87% in
      group I and 33% in group II ( P </= 0.02).

PMID- 15236000
TI  - Timing of injection and plasma concentration of lidocaine before endotracheal
      intubation.
AB  - The optimal time of intravenous lidocaine for attenuation of pressor responses to
      laryngoscopy and endotracheal intubation was evaluated in fifty adult patients
      and the correlation between plasma lidocaine level and its clinical effects were
      also studied. The plasma lidocaine levels were highest 0.5 min after
      administration of lidocaine 1.5 mg.kg(-1) intravenously. However, endotracheal
      intubation 0.5 min after lidocaine administration caused significant increase in
      mean arterial pressure (MAP) and heart rate (HR). Mean arterial pressure and HR
      increased with endotracheal intubation following 1, 2 and 3 min after lidocaine
      administration, but the magnitude of increase was not statistically significant.
      There were no significant differences in MAP changes among these three groups. It
      was concluded that the plasma lidocaine levels did not correlate with its
      suppressive effect on circulatory responses due to laryngoscopy and endotracheal
      intubation. Laryngoscopy and endotracheal intubation should be carried out at
      least 1 min after intravenous lidocaine administration.

PMID- 15236001
TI  - Comparative study of intravenous administration of Ringer's lactate, Ringer's
      acetate and 5% glucose containing these Ringer's solutions in human being.
AB  - The effects of the administration of Ringer's lactate (L) and Ringer's acetate
      (A) solution on blood biochemistry in human subjects operated for tympanoplasty
      under general anesthesia were investigated. And the feasibilities of the clinical
      use of Ringer's lactate (LD) and Ringer's acetate (AD) solution containing 5%
      glucose were also assessed. In all cases the rate of infusion was 500 ml for
      initial 20 min, and then 5 ml.hr(-1).kg(-1) B.W. for 3 hr and 10 min. There were
      significant increases in blood L- and D-lactate, pyruvate, and L-lactate/pyruvate
      ratio in L group. A significant increase in blood acetate but not lactate was
      found in A group. These metabolic changes were minimal and considered as
      clinically not significant. The urinary excretion of lactate, pyruvate, acetate
      and glucose were also negligible. In both LD and AD group, the higher blood
      concentrations of lactate, pyruvate, acetate and glucose were found than in L and
      A group. Urinary excretions of these metabolites were much higher in LD and AD
      group than in L and A group. So glucose containing Ringer's lactate or acetate
      solutions should be administered in appropriate amounts and rate not to induce
      clinically significant metabolic alterations.

PMID- 15236002
TI  - Anesthetic management of the patient with a history of Kawasaki disease--a report
      of 19 cases.

PMID- 15236003
TI  - Anesthetic management of an infant with a solitary mastocytoma.

PMID- 15236004
TI  - Periodic isorhythmic dissociation during enflurane anesthesia in a patient with
      sinus bradycardia.

PMID- 15236005
TI  - Hemodynamic effect of diltiazem cardioplegia following cardiopulmonary bypass.

PMID- 15236006
TI  - Anesthetic management for a patient with renal arterio-venous fistula.

PMID- 15236007
TI  - The significance of hematuria in the patient with ruptured abdominal aortic
      aneurysm.

PMID- 15236008
TI  - Hemodynamic changes during liver resection with monitoring right ventricular
      ejection fraction (RVEF).

PMID- 15236009
TI  - Preforming of a nasal endotracheal tube to avoid obstruction.

PMID- 15236010
TI  - Comparative inotropic effects of local anesthetics in isolated cat papillary
      muscles.
AB  - The direct inotropic action of seven local anesthetics: procaine, mapivacaine,
      lidocaine, tetracaine, chloroprocaine, bupivacaine and etidocaine were compared
      in isolated cat papillary muscles. All of the local anesthetics produced a dose
      related depression of maximal velocity of shortening (Vmax), maximal developed
      force (Fm) and maximal dF/dt. The more potent local anesthetics such as
      bupivacaine and etidocaine depressed myocardial contractility at significantly
      lower concentrations than the less potent local anesthetics such as lidocaine and
      mepivacaine. Depression of Vmax by bupivacaine or etidocaine was three times
      greater than that by lidocaine and ten times greater than that by procaine. At
      the same concentration (10(-4) M), direct myocardial depression was demonstrated
      in the following order of severity: etidocaine >/= bupivacaine >> tetracaine >>
      chloroprocaine >/= lidocaine >> mepivacaine >> procaine.

PMID- 15236011
TI  - The ventilation management during the reconstruction of the tracheo-bronchial
      tree in adults.
AB  - The most important point of anesthetic management during the reconstruction of
      the tracheo-bronchial tree (TBT) is to secure the airway and to maintain adequate
      ventilation. We experienced 17 cases of reconstruction of the TBT. Various
      methods of ventilation were achieved; one-lung ventilation, right middle and
      lower lobes ventilation, and combinations of these. We used double-lumen tubes,
      single-lumen tubes with or without blocker, spiral tubes, and intravenous
      catheters. We selected an appropriate ventilation method suitable for the diverse
      operative modes and achieved satisfactory managements during operation.

PMID- 15236012
TI  - Analgesia and respiratory function following intrapleural bupivacaine after
      cholecystectomy.
AB  - Analgesia and pulmonary function following intrapleural bupivacaine were compared
      with those following intramuscular pethidine in thirty-four patients after
      cholecystectomy. The patients were randomly allocated to two groups of seventeen
      patients each to receive either intrapleural bupivacaine or intramuscular
      pethidine. The positions of seventeen intrapleural catheters inserted were
      confirmed by chest radiography. Two out of seventeen catheters were found to be
      located in the extrapleural space. It was also recognized by fluoroscopy that
      phrenic nerve palsy did not develop on patients given intrapleural bupivacaine.
      The subjective quality of analgesia following intrapleural bupivacaine was
      significantly better than that following intramuscular pethidine. The mean
      duration of analgesia obtained after each injection of bupivacaine was 4.68 hr
      (range 3.5-6.1 hr). Forced vital capacity (FVC) and forced expiratory volume in 1
      second (FEV 1), which decreased markedly in the postoperative period improved
      significantly after being given bupivacaine or pethidine. But there was no
      significant difference in the improvement of FVC and FEV 1, between both groups
      in spite of the higher percentage of pain relief in the intrapleural bupivacaine
      group. All respiratory function tests studied thirty days after surgery were not
      significantly different when compared with those before surgery.

PMID- 15236013
TI  - Pulmonary hypertensive response to declamping of the aorta during abdominal
      aortic reconstructive surgery-role of metabolic derangement and anaphylatoxin in
      the reaction.
AB  - Metabolic parameters and anaphylatoxin activities in mixed venous blood were
      measured in 16 patients undergoing abdominal aortic reconstructive surgery to
      study the mechanism of pulmonary hypertensive response after aortic declamping.
      This reaction was confirmed by a rise in ratio between mean pulmonary arterial
      pressure and mean systemic arterial pressure (Pp/Ps). Aortic declamping was
      followed by a significant increase in lactate level and lactate-pyruvate ratio
      (L/P ratio) as compared with pre-declamping level ( P << 0.01). Although
      anaphylatoxin C3a concentration rose significantly after declamping ( P << 0.01),
      C5a showed no change at any stage. When the patients were divided into two groups
      according to the degree of Pp/Ps change by declamping, significant elevation of
      L/P ratio and C3a level were observed in the group with higher increase (Post
      /Pre-declamp value >/=1.25) of Pp/Ps compared to the lower (>>1.25) group. After
      declamping, in the higher Pp/Ps group, a positive correlation existed not only
      between Pp/Ps change and aortic clamp time, but also between L/P ratio and C3a
      level. The present results suggest that muscular metabolic derangement distal to
      the aortic clamp may play an important role in the development of post-declamping
      pulmonary hypertensive response through anaphylatoxin C3a.

PMID- 15236014
TI  - Optimum dose of epidural morphine for postsurgical analgesia.
AB  - To determine the optimum dose of epidural morphine for postoperative pain
      control, 0.5-4.0 mg of morphine was administered to 198 patients who had
      undergone operations on lower abdomen or lower extremities under continuous
      epidural anesthesia. Analgesic effect of morphine and incidence of nausea or
      vomiting were studied using linear discriminant analysis. As explanatory
      variables, age and dose of morphine were statistically significant in
      discriminating analgesic effect of morphine. Among indices for physique of
      patients, height was the most useful for predicting the analgesic effect. The
      dose which made the discriminant function zero corresponded to the minimum
      effective dose (MED) of morphine and it was expressed as follows; MED (mg.meter(
      1)) = -0.0107 x age + 1.85. Predicting the incidence of nausea or vomiting in
      relation to the dose of morphine did not reach a level of statistical
      significance.

PMID- 15236015
TI  - The effects of ulinastatin on cardiac and hepatic energy metabolism in rats
      subjected to hypovolemic shock.
AB  - Ulinastatin is a trypsin inhibitor extracted from human urine. In this study the
      effects of ulinastatin on myocardial and hepatic tissue concentrations of
      creatine phosphate (CP), ATP, ADP, AMP, lactate, pyruvate, and glycogen have been
      investigated in rats which were in hemorrhagic shock state. Hypovolemia was
      induced by bleeding from the femoral artery, and systolic blood pressure was
      maintained 40 mmHg for 25 min, then ulinastatin 50,000 units.kg(-1) in saline or
      saline vehicle was intravenously administered. Thereafter the heart and liver
      were extirpated and frozen quickly with liquid nitrogen. The tissue
      concentrations of CP, ATP, ADP, AMP, lactate and glycogen were measured
      enzymatically. Systolic blood pressure elevated significantly after ulinastatin
      administration. The myocardial tissue CP level was higher in ulinastatin-treated
      group than that of control group, whereas no significant difference in energy
      charge between two groups. The hepatic tissue level of AMP, lactate and L/P ratio
      was lower in ulinastatin-treated group than that of control group, however, no
      significant difference was found in hepatic tissue level of ATP, ADP and energy
      charge. From these results it is concluded that ulinastatin can improve the
      energy metabolism of myocardium to some extent, but not of the liver in rats with
      hypovolemic shock.

PMID- 15236016
TI  - The cardiovascular effects of atracurium and it's metabolite.
AB  - The administration of atracurium to humans has been reported to produce little
      cardiovascular effects in clinical doses. The cardiovascular effect, histamine
      releasing and catecholamine releasing effects of intravenous injection of
      atracurium 0.6 and 1.2 mg.kg(-1) were studied in man, and also the cardiovascular
      and catecholamine releasing effects of laudanosine which is a metabolite of
      atracurium by Hofmann degeneration, were studied in dogs. The increase in human
      plasma concentration of histamine, hypotension and tachycardia were found with
      the dose of atracurium 1.2 mg.kg(-1). The intravenous administration of
      laudanosine 10 micro g.kg(-1) to dogs produced minimal epinephrine,
      norepinephrine releases and cardiovascular changes.

PMID- 15236017
TI  - Effects of nitrous oxide on the somatosensory evoked response in cats.
AB  - The effect of nitrous oxide on the activity of the somatosensory system was
      studied in cats with brain electrodes implanted chronically. The electrodes were
      implanted in the primary somatosensory cortex, cortical somatosensory radiation,
      medial lemniscus and midbrain reticular formation. Alterations in the
      excitability of the primary sensory pathway were assessed by the changes of the
      input to and output from these brain areas: the response in the medial lemniscus
      to the stimulation of the skin represented the input to the thalamic relay
      nucleus and the response recorded in the cortical sensory radiation represented
      the output from the thalamic relay nucleus. The concentrations of nitrous oxide
      studied were 50% and 75% in oxygen, and the drug effect was concentration
      related. The cortical response to peripheral stimulation was suppressed in
      amplitude by more than 40% of the control with 75% nitrous oxide, and the
      response in the cortical radiation was suppressed by 20% of the control with the
      same dose of nitrous oxide. The response in the cortical radiation to stimulation
      of the medial lemniscus was suppressed by 20% of the control and the postsynaptic
      component of the cortical response to the stimulation of the medial lemniscus was
      suppressed by more than 50% of the control. The multi-unit activity of the
      brainstem reticular formation was enhanced by nitrous oxide in a dose related
      manner. The excitability of the thalamic relay nucleus and the primary
      somatosensory cortex was suppressed by natural slow wave sleep when the reticular
      multi-unit activity was suppressed, and they were enhanced by paradoxical phase
      of sleep when the reticular multi-unit activity was enhanced. These findings
      indicated that the degree of suppression of excitability by nitrous oxide is
      similar in both the thalamic relay nucleus and sensory cortex, and its action on
      the brain stem reticular formation is different from that on the primary sensory
      system. The suppression of sensory functions shown in the present study provides
      a certain clue to the understanding of the neural basis that though nitrous oxide
      does not produce deep surgical anesthesia, it does induce potent analgesia and
      sedation during surgery.

PMID- 15236018
TI  - Dose calcium balanced heparin affect blood gas and electrolyte analysis?
AB  - The effect of calcium-balanced heparin (471896, CIBA CORNING) on blood gas and
      electrolyte analysis was evaluated, by comparing with that of sodium heparin (Na
      heparin). One ml of whole blood was collected into a syringe, which contained
      calcium-balance heparin (Ca balanced heparin) or Na heparin. 122 pairs of blood
      samples obtained from 15 patients were analyzed for Na, K, ionized calcium
      (Ca(++)), total hemoglobin, pH, P(CO)(2), and P(O)(2) by an automatic blood gas
      and electrolyte analyzer, CIBA CORNING model 288. There was a significant
      difference ( P << 0.05) in pH, P(CO)(2), Na, and Ca(++) between the two different
      groups. Ca(++) concentration was significantly less in Na heparin group than in
      Ca balanced heparin group, probably due to more chelation of Ca(++) by Na heparin
      than Ca balanced heparin. The present study suggests that the Ca balanced heparin
      has minimal effect on the blood gas and electrolyte analysis, and is a suitable
      anticoagulant for the Ca(++) measurement.

PMID- 15236019
TI  - Sevoflurane anesthesia for elective cesarean section.
AB  - Sevoflurane anesthesia was given to sixteen women who had been scheduled for
      elective cesarean section. The maternal systolic blood pressure significantly
      decreased during the anesthesia induction. Both the anesthesia induction and
      emergence were smooth and rapid. These findings were supported partially by the
      pharmacokinetic analysis of sevoflurane concentration in the maternal artery and
      expired gas mixture. Spontaneous uterine contractions were good in 12 patients,
      fair in two and poor in two. The measured blood loss was 752 +/- 257 ml including
      amniotic fluid. No blood transfusion was given to any patient. The median value
      of the Apgar score at one minute was seven (range three to nine). No neonate was
      intubated for resuscitation. No abnormal maternal laboratory data were found,
      including liver and kidney function tests and blood cell counts one week after
      the operation. No adverse effect of sevoflurane on the neonate was found one week
      after the delivery and three months after the discharge.

PMID- 15236020
TI  - The present status of casualty care in Japan and the role of anesthesiologists.

PMID- 15236021
TI  - Diazepam prevents fentanyl-induced muscle rigidity.

PMID- 15236022
TI  - A case of trigeminal neuropathy.

PMID- 15236023
TI  - Transcutaneous electrical nerve stimulation for relief of pain of venopuncture.

PMID- 15236024
TI  - A comparative study of measurement of arterial blood pressure using HEM-802F and
      arterial cannulation.
AB  - Finger arterial blood pressures determined by a newly developed sphygmomanometer,
      HEM-802F, were compared with arterial pressure obtained from direct measurement
      of the radial artery. An excellent correlation was found between the two methods
      (systolic: r = 0.93, diastolic: r = 0.91), although there was a large variability
      among individual subjects. The range of differences between them are from +32 to 
      13 mmHg for systolic and +15 to -25 mmHg for diastolic blood pressure
      measurement. HEM-802F underestimated systolic pressure (-4.0 mmHg) and
      overestimated diastolic pressure (+6.7 mmHg), compared with intra-arterial
      readings. The HEM-802F was useful for the non-invasive arterial pressure
      monitoring during general anesthesia.

PMID- 15236025
TI  - Effects of sevoflurane on autonomic nerve activities controlling cardiovascular
      functions in rats.
AB  - Effects of different inspiratory concentrations of sevoflurane (fluorometyl
      1,1,1,3,3,3,-hexafluoro-2-propylether) on blood pressure, heart rate and efferent
      activities of cardiac sympathetic, cardiac parasympathetic and renal sympathetic
      nerves were examined using rats either under the resting condition or during
      noxious mechanical stimulation of a hindpaw. Under the resting condition, an
      increase in the inspiratory concentration of sevoflurane from 2.1% to 4.2%
      gradually caused a decrease in blood pressure and heart rate. With the increase
      in the sevoflurane concentration, cardiac sympathetic nerve activity decreased,
      whereas renal sympathetic nerve and cardiac parasympathetic nerve activities did
      not change significantly. When noxious mechanical stimulation was applied to a
      hind-paw by pinching, blood pressure and heart rate, renal sympathetic and
      cardiac sympathetic nerve activities all increased at the 2.1% concentration of
      sevoflurane. The responses of these parameters were attenuated at the 3.1%
      concentration of sevoflurane and almost disappeared at the 4.2% concentration.
      Cardiac parasympathetic nerve activity did not change significantly during the
      pinching stimulation throughout the 2.1-4.2% concentration increase.

PMID- 15236026
TI  - Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in
      dogs.
AB  - We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and
      enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen
      consumption in 14 mongrel dogs randomly divided into groups of seven each.
      Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were
      measured continuously using ultrasonic transit time flow meter. Mean arterial
      blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic
      oxygen consumption (HVO2) were measured. Halothane significantly deceased HABF,
      but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF
      significantly. MAP and CI decreased in both groups, with halothane producing more
      marked decreases than enflurane. HVO2 did not change with enflurane, but did with
      halothane, producing significant differences, with halothane being greater at
      1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The
      results suggest that liver blood flow and oxygen consumption are affected
      differently by halothane and enflurane and that halothane has a stronger tendency
      to cause an imbalance between liver oxygen supply and consumption than dose
      enflurane.

PMID- 15236027
TI  - The effects of anesthesia and surgery on count and function of neutrophils.
AB  - The effects of anesthesia and surgery on neutrophil count, chemotaxis and
      neutrophil alkaline phosphatase (NAP) score were investigated in 10 patients who
      had elective spine surgery. Plasma levels of adrenaline, noradrenaline and
      cortisol were measured and correlations between hormonal levels and neutrophil
      count and function were assessed. Neutrophil count started increasing after the
      initiation of surgery, reached the highest level at 3 hours after surgery, and
      decreased gradually toward preanesthetic level on 3rd postoperative day. The
      increase in band cell: segment cell ratio is prominent, whereas lymphocytes
      decreased significantly. Neutrophil chemotaxis and spontaneous migration were
      increased significantly from the end of operation to 1st postoperative day. NAP
      score, assumed to reflect the neutrophil phagocytic activity, lowered transiently
      during anesthesia, then increased 1.6 times more than preanesthetic level on 1st
      postoperative day. It was indicated that the increased cortisol release rather
      than adrenaline due to body response to surgical stress might induce
      neutrophilia, and that the elective spine surgery might not be deleterious to the
      neutrophil function.

PMID- 15236028
TI  - Circulatory responses to epidural blockade of treated and untreated hypertensive
      patients.
AB  - The circulatory effects of epidural blockade were studied in 82 hypertensive
      patients. To compare the circulatory responses to epidural blockade between
      treated and untreated hypertensive patients, patients were divided into 60
      treated and 22 untreated hypertensive patients groups, and to confirm the
      magnitude of hemodynamic changes according to the segment of epidural approach,
      each group was then subdivided into 3 groups as cervical, thoracic and lumbar.
      The blood pressure and the pulse rate were measured before and after
      establishment of epidural blockade. The baseline blood pressure of untreated
      group was significantly higher than that of treated one (P < 0.05), but there was
      no difference between two groups in the initial pulse rate. At 20 min after
      meperidine administration to epidural space, blood pressure drop was more
      pronounced in untreated thoracic subgroup than in treated one (P < 0.05), but
      there was no significant difference in blood pressure drop between treated and
      untreated groups of cervical and lumbar blockade. Regarding the pulse rate
      change, there was no significant difference between treated and untreated cases
      of all the subgroups. The rate of fluid load required to maintain the adequate
      blood pressure in the first 20 min of epidural blockade was more in treated than
      in untreated cases of cervical subgroup. During surgery the administration of
      vasopressor agents was more frequently required to maintain blood pressure in
      treated and untreated thoracic subgroups, while the administration of vasodilator
      agents was more frequent in treated and untreated cases of cervical and thoracic
      subgroups. The incidence of rebound hypertension was relatively high in untreated
      cervical and thoracic subgroups as compared to treated ones.

PMID- 15236029
TI  - Effect of diltiazem on hypoxic pulmonary vasoconstriction in dogs.
AB  - We have examined the effect of diltiazem upon the pulmonary vascular response to
      the left lower lobe (LLL) hypoxia in dogs. Without diltiazem, the fraction of
      cardiac output perfusing the LLL (QLLL/QT) measured by the ultrasonic doppler
      rheometer in the hypoxic phase was 21.0 +/- 11.7(%) of the ratio in the first
      normoxic phase. When diltiazem was given as a 0.48 mg/kg intravenous bolus
      followed by an intravenous infusion of 0.48 mg/kg/hr and 0.96 mg/kg intravenous
      bolus followed by an intravenous infusion of 0.96 mg/kg/hr, QLLL/QT in the
      hypoxic phase were 34.0 +/- 14.0, 48.6 +/- 16.1(%) of the ratio in the first
      normoxic phase respectively. Significant difference was observed at all diltiazem
      concentrations. With respect to PaO2, significant difference was not observed at
      all diltiazem concentrations in the ratio of the hypoxic phase to the first
      control phase. So we concluded that diltiazem obviously attenuated hypoxic
      pulmonary vasoconstriction (HPV) response but did not decrease PaO2 because of
      keeping myocardial oxygen balance and better ventilation/perfusing relationship.

PMID- 15236030
TI  - Effects of sevoflurane with or without nitrous oxide on cardiac contractility and
      sinoatrial node rate.
AB  - Cardiac effects of sevoflurane (SE) with or without nitrous oxide were examined
      in the canine blood-perfused papillary muscle and sinoatrial node preparations.
      Although SE depressed developed tension (DT), mean arterial pressure (MAP) and
      heart rate of the donor dog (DHR) dose dependently, sinoatrial rate (SAR) was not
      changed significantly. No significant changes in MAP, DHR and SAR were observed
      with the addition of nitrous oxide to SE. However, the addition of nitrous oxide
      to SE resulted in significant decrease of DT. These results suggest that SE
      depresses BP and cardiac contractility dose dependently, but dose not change
      heart rate. The combination of nitrous oxide and SE may produce less
      cardiovascular depressant effect at a given MAC level than SE given alone.

PMID- 15236031
TI  - The effect of hyperoxia on the lungs of rats deficient in essential fatty acids.
AB  - Morphological alterations in the lungs of rats deficient in either or both of
      vitamin E and essential fatty acids were investigated after exposure to hyperoxia
      for 48 h. In rats deficient in both vitamin E and essential fatty acids, there
      was damage to type-2 alveolar cells observed as swollen mitochondria and bleb
      formation in the cytoplasm. None of these changes was found in rats deficient in
      only one of these substances. Hyperoxia in rats deficient in both substance also
      caused destruction of the capillary endothelial cells and edema in the
      interstitium. The lungs of rats deficient in only one of the substances showed
      some edema in the capillary endothelial cells, but not destruction, and less
      interstitial edema. These findings suggest that simultaneous deficiency in
      vitamin E and essential fatty acids facilitates lung damage in rats exposed to
      hyperoxia.

PMID- 15236032
TI  - Evaluation of shock-related cardiotoxic peptide.
AB  - The aim of the present work is to confirm the presence of MDF (myocardial
      depressant factor), which has long been postulated to be one of the cardiotoxic
      substances in the shock state. Twenty male mongrel dogs were divided into two
      groups, a hemorrhagic shock group (n = 10) and an endotoxic shock group (n = 10).
      Blood samples were obtained from each animal at 1, 2, 4, and 7 h after
      hypotensive events occurred. Inotropic properties of the plasma samples were
      evaluated by the isometric contraction of a cat papillary muscle preparation, and
      chromatographic analysis was performed on the peptides in the plasma. Developed
      tension of the muscle was increased significantly by changing the bathing medium
      from Krebs-Henseleit solution to plasma obtained 1 to 4 h after the onset of
      hemorrhagic and endotoxin induced hypotension. The positive inotropic change was
      associated with a significant increase in plasma epinephrine concentration. None
      of these plasma samples possessed a negative inotropic effect (i.e., the property
      of MDF activity). The elution profile by gel column chromatography of samples
      obtained from shocked animals was almost identical to that recognized as MDF.
      However, the presence of MDF was not confirmed by column parameters and color
      development by the ninhidrin reaction. In conclusion, we found no evidence to
      support the presence of cardiotoxic peptide in plasma of shocked animals.

PMID- 15236033
TI  - Evaluation of ejectors using the venturi effect for a continuous positive airway
      pressure system without compressed air.
AB  - The purpose of this study is to perform a test in the application of the existing
      ejectors with the continuous positive airway pressure (CPAP) system without
      compressed air. Four types of ejector (jet mixer, the former and new puritan
      nebulizer and the deluxe nebulizer) for blending oxygen and room air by the
      Venturi effect were tested. A decrease of mixed gas flow and an increase of
      oxygen concentration were observed according to the increase of positive pressure
      in all systems. The former puritan nebulizer and deluxe nebulizer were found to
      be unavailable for the CPAP system for high oxygen concentration and low mixed
      gas flow for the increase of positive pressure. In the system, however, with the
      new puritan nebulizer and jet mixer, a sufficient mixed gas flow and an
      appropriate oxygen concentration could be supplied at an adequate positive
      pressure. The CPAP system using only oxygen was judged as possibly giving
      availability.

PMID- 15236034
TI  - Protein kinase C and simulated ischemia possible aberrations of signal
      transduction during ischemia.
AB  - ATP depletion is always associated with prolonged ischemia. It was found that ATP
      affected calcium- and phospholipid-dependent activation of protein kinase C
      without hydrolysis of the nucleotide when the activation was monitored by an
      assay for [3H] 4-beta-phorbol-12, 13-dibutyrate binding activity in a
      reconstitution system having physiological concentrations of free calcium. When
      the ATP level was low, an increase in the free calcium concentration could not
      activate the enzyme. A decrease in pH exacerbated the depressed activation. The
      concentration of magnesium also affected the activation. On the other hand, free
      fatty acids, which increase during ischemia, were able to activate the enzyme at
      a low concentration of ATP in the absence of phorbol ester and
      phosphatidylserine. These results suggest that calcium- and phospholipid
      dependent activation of protein kinase C is suppressed during ischemia, and that
      fatty acids in turn activate the enzyme. It is possible that ischemia interferes
      with normal signal transduction via the protein kinase C pathway and causes
      unusual protein phosphorylation.

PMID- 15236035
TI  - Clinical evaluation of esophageal doppler cardiac output measurement during
      general anesthesia.
AB  - We evaluate the accuracy of cardiac output measurement with esophageal Doppler
      ultrasonography (ECO). A total of 71 simultaneous measurement of esophageal
      Doppler and thermodilution cardiac output were compared in 16 patients undergoing
      general anesthesia in the supine position. ECO was determined easily with minimal
      experience, and significantly correlated with thermodilution cardiac output
      (TDCO) measurement ( P < 0.001). The regression equation obtained was Y = 0.983X
      + 0.019, and the correlation coefficient was 0.935. Furthermore, ECO was more
      reproducible than TDCO. However, ECO is not able to assess CO accurately in
      either lateral or prone position and after cardiopulmonary bypass in open heart
      surgery. Our results suggest that the esophageal Doppler technique allows a
      noninvasive and continuous cardiac output monitoring in patients during general
      anesthesia, and that it is more useful in patients for whom invasive monitoring
      is considered inappropriate. However, further improvement in this technique will
      be necessary for its routine use in clinical anesthesia.

PMID- 15236036
TI  - Cardiopulmonary responses to the tracheobronchial suction with a fiberoptic
      bronchoscope during and after anesthesia.
AB  - The cardiopulmonary responses to endobronchial suction with a fiberoptic
      bronchoscope (FOB suction) during and after anesthesia were compared in 12
      patients underwent elective surgeries. FOB suction for 1 mm was performed during
      enflurane anesthesia (1.5% enflurane in oxygen) with muscle relaxant
      (anesthetized stage) and after anesthesia during spontaneously breathing of
      oxygen (awake stage). FOB suction lowered PaO2 to a greater extent in the awake
      than in the anesthetized stage. Mean PaO2 decreased from 414 to 111 torr in the
      awake and from 447 to 333 in the anesthetized stage. During suction, PaCO2
      slightly increased in both stages. In response to FOB suction, heart rate
      increased significantly in the awake stage (P < 0.001), while mean blood pressure
      increased significantly in the anesthetized stage (P < 0.01). These findings
      indicate that the cardiopulmonary responses to FOB suction for 1 min during and
      after anesthesia differed. The procedure might be less dangerous during
      anesthesia.

PMID- 15236037
TI  - Continuous mixed venous oxygen saturation monitoring during general anesthesia.
AB  - Clinical evaluation of continuous SvO2 monitoring during general anesthesia was
      made in 21 surgical patients utilizing a fiberoptic reflectometry system combined
      with a pulmonary artery flow-directed balloon catheter. On-line in vivo values
      for SvO2 by the system were closely related to those obtained in vitro from a
      Radiometer ABL-300. There was a good correlation between changes of in vivo SvO2
      and corresponding changes in cardiac index. We also observed that there were
      significant correlations between SvO2 and oxygen extraction ratio, and SvO2 and
      oxygen delivery. These data indicate that continuous monitoring of SvO2 during
      general anesthesia can provide on-line information not only about hemodynamic
      state but also on oxygen transport, which will be especially helpful in managing
      hemodynamically unstable patients during anesthesia.

PMID- 15236038
TI  - Effects of alveolar hypoxia on pulmonary capillary beds.
AB  - Using open chested dogs (n = 12), we tested the hypothesis that the pulmonary
      capillary changes its caliber in response to alveolar hypoxia. Animals were
      placed in a left upright lateral position. Pulmonary perfusion was measured by
      electromagnetic flow transducers attached to the main and left pulmonary
      arteries. Systemic artery, pulmonary artery and pulmonary vein pressures were
      measured via catheters inserted into them. Shunt flow through the pulmonary
      capillary beds was evaluated by the microsphere method, injecting a mixture of
      three different size (3, 9 and 15 microm) radioactive microspheres into the
      inferior vena cava. Right one lung ventilation with left lung atelectasis or left
      lung insufflation of 5 cmH2O (O2 or He) was achieved by occluding the left main
      bronchus with a blocker attached to an endotracheal tube. Right one lung
      ventilation caused redistribution of the perfusion from the left lung to the
      right lung. Left pulmonary vascular resistance increased significantly, while
      total pulmonary vascular resistance showed no significant changes. The shunt
      ratios of the 3 and 9 microm microspheres were not changed by right one lung
      ventilations with left lung atelectasis or insufflation. The shunt ratio of the 3
      microm microspheres through the left lung was significantly higher than that
      through two lungs during both the two lung and one lung ventilations. We
      concluded that caliber changes in the pulmonary capillary do not occur in
      response to alveolar hypoxia.

PMID- 15236039
TI  - Effects of various catecholamines on high-energy phosphates of rat liver and
      brain during hemorrhagic shock measured by 31P-NMR spectroscopy.
AB  - The effects of dopamine, epinephrine and norepinephrine on energy metabolism as
      well as intracellular pH in rat liver and brain during hemorrhagic shock were
      examined by in vivo 31P-NMR spectroscopy. The hemorrhagic shock was induced by
      arterial bleeding to a mean arterial pressure (MAP) of 30-40 mmHg. Upon the
      induction of hemorrhagic shock, there was a dramatic fall in adenosine
      triphosphate (ATP) and a rise in inorganic phosphate (Pi) in the liver. The
      intracellular pH indicated severe acidosis. However, no change in these
      parameters was observed in the brain during hemorrhagic shock. After infusion of
      the above catechollamines following 10 min of hemorrhagic shock, MAP increased to
      90-100% of its control value. Only dopamine improved hepatic energy metabolism,
      whereas brain energy metabolism was not affected by any of them. This suggests
      that dopamine protects liver function during hemorrhagic shock without affecting
      brain energy metabolism.

PMID- 15236040
TI  - The hemodynamic and metabolic changes in prostaglandin E1-induced hypotension in
      dogs--a comparative study with trimetaphan-induced hypotension.
AB  - The hemodynamic and metabolic changes in hypotensive state induced with
      prostaglandin E1 (PGE1) or trimetaphan (TMT) infusion were investigated in dogs.
      Mean arterial pressure was decreased by about 50% with 1.58 microg/kg/min of PGE1
      or 45 microg/kg/min of TMT. Heart rate, pulmonary capillary wedge pressure and
      central venous pressure remained virtually unchanged in the two groups. Cardiac
      output was well maintained in PGE1 group, whereas cardiac output showed the
      tendency to decline in TMT group. Greater reduction in systemic vascular
      resistance was seen in PGE1 group than in TMT group. Pulmonary vascular
      resistance showed no significant change in PGE1 group, whereas it increased
      significantly in TMT group. Gradual decreases in arterial pH, PaO2 and base
      excess and slight but significant increase in PaCO2 was observed in PGE1 group,
      and these abnormalities recovered 30 min after hypotension. Abnormalities in
      blood gases and acid-base balance were considerably more severe and prolonged in
      TMT group compared with those in PGE1 group. Blood lactate and pyruvate
      concentrations showed no significant changes in PGE1 group, whereas substantial
      elevation was seen in L/P ratio especially 30 min after induction of hypotension
      in TMT group. Oxygen consumption showed minimal changes in PGE1 group, whereas a
      significant decrease was observed in TMT group. The conclusions derived from
      these results are as follows; 1) PGE1 maintained cardiac output better than TMT,
      probably because of its direct inotropic action on the heart, and of its greater
      reduction of systemic vascular resistance than TMT. 2) PGE1 seemed to provide the
      better blood perfusion throughout the body than TMT. 3) PGE1 showed less
      possibility to produce the metabolic derangement compared with TMT.

PMID- 15236041
TI  - Effects of intravenously administered human atrial natriuretic peptide on
      elevated blood pressure during surgery.
AB  - The effect of human atrial natriuretic peptide (hANP) on blood pressure (Bp) was
      evaluated in 11 patients who had elevated systoric Bp of over 150 mmHg during
      surgery. A bolus injection of 50 microg or 100 microg of hANP decreased Bp with
      an immediate response by 27.6 +/- 3.1 mmHg (P < 0.001) or 40.7 +/- 4.2 mmHg (P <
      0.001), respectively, accompanying with tremendously increased urine output.
      Heart rate and PaO2 were not altered. Thus, a intravenous bolus injection of hANP
      is an useful therapeutic tool for the treatment of acutely elevated Bp during
      anesthesia.

PMID- 15236042
TI  - Anesthesia for a patient with recessive dystrophic epidermolysis bullosa.
AB  - Two different anesthetic methods were employed for a patient with recessive
      dystrophic epidermolysis bullosa (R-DEB). One was plexus brachial block in
      combination with ketamine infusion. The other was general anesthesia with N2O-O2
      halothane via a face mask. In the former, no particular problem developed. In the
      later, however, some blisters were newly formed on the region where the
      anesthesist's fingers were attached to hold a face mask. Although mask anesthesia
      was considered to be not always suitable for patients with DEB, we chose it
      because tracheal intubation may cause more serious damage to the upper airway
      leading to airway obstruction.

PMID- 15236043
TI  - Anesthesia for a patient with Williams syndrome.

PMID- 15236044
TI  - Emergency needle cricothyrotomy may not be useful in case of tracheal collapse.

PMID- 15236045
TI  - Cardiovascular effects of hyoscine butylbromide in pediatric halothane
      anesthesia.

PMID- 15236046
TI  - Anesthesia and hyperparathyroidism.

PMID- 15236047
TI  - Accelerated reversal of pancuronium blockade with divided administration of
      neostigmine.

PMID- 15236048
TI  - Effects of anesthetic and related agents on calcium-induced calcium release from
      sarcoplasmic reticulum isolated from rabbit skeletal muscle.
AB  - We have investigated the effects of anesthetic and related agents on Ca(2+)
      induced Ca2+ release (CICR) in heavy sarcoplasmic reticulum isolated from rabbit
      skeletal muscle. The purpose of this study is to elucidate their possible role as
      triggering agents in malignant hyperthermia (MH). None of the agents (ketamine,
      procaine, lidocaine, succinylcholine, pancuronium and fentanyl) affected CICR at
      clinical concentrations. At higher concentrations, procaine, pancuronium and
      succinylcholine inhibited CICR, but ketamine rather potentiated it. It is
      unlikely that lidocaine is a potent facilitator of CICR at any concentrations. We
      conclude that procaine, lidocaine, non-depolarizing muscle relaxants and opiate
      can be used safely for MH susceptible patients and that ketamine and
      succinylcholine are not recommended.

PMID- 15236049
TI  - Renal tissue gas tensions during hemorrhagic shock.
AB  - To evaluate the development of renal hypoxia during hemorrhagic shock, fourteen
      dogs were induced in this study. The animals were divided equally into a group in
      which mean arterial pressure (MAP) was kept at 50 mmHg (group 1), and into
      another where MAP was kept at 40 mmHg for 180 min (group 2). Renal tissue gas
      tensions were determined by a mass spectrometer. In the 50-mmHg group, renal
      tissue oxygen tension (PrO2) dropped for 15 min following hemorrhage, remained
      constant for 90 min, then fell further for 150 min before a plateau was
      established. In the 40-mmHg group, the PrO2 dropped for 90 min before reaching a
      plateau. The second PrO2 decline occurred at the same level in both the 50-mmHg
      group and the 40-mmHg group. The point at which the same PrO2 level occurred for
      each group suggests the cessation of oxygen consumption and the conditions of
      renal hypoxia. It is assumed that renal hypoxia occurs in 120 min at a MAP of 50
      mmHg and in 60 min at a MAP of 40 mmHg.

PMID- 15236050
TI  - Effects of tracheal insufflation of oxygen (TRIO) on blood gases during external
      cardiac compressions in dogs under ventricular fibrillation.
AB  - Tracheal insufflation of oxygen (TRIO) is a form of constant-flow ventilation. We
      studied the effect of TRIO at a flow rate of 2 L/kg/min on arterial blood gases
      during external cardiac compressions in dogs with ventricular fibrillation.
      During the combined application of TRIO and external cardiac compressions, all
      animals were adequately oxygenated and hyperventilated except in cases where lung
      edema developed in the course of cardiopulmonary resuscitation (CPR). No
      pulmonary barotrauma was observed. The findings suggest that TRIO might be used
      as a temporary measure for emergency ventilation when CPR is performed in certain
      situations such as upper airway abnormalities or cardiac arrest outside the
      hospital setting, where intermittent positive pressure ventilation is not
      feasible.

PMID- 15236051
TI  - Effects of sevoflurane on myocardial metabolism during postischemic reperfusion
      in the rat.
AB  - In experiments on isolated rat heart lung preparation, the effects of sevoflurane
      on myocardial metabolism during postischemic reperfusion were evaluated with
      intramyocardial high energy phosphates, lactate and glycogen. Hearts were
      perfused for 10 min initially and made globally ischemic for 8 min. Afterwards,
      they were reperfused for 12 min. Sevoflurane was administered from 5 min after
      the start of perfusion to the end of reperfusion. There was no significant
      difference in myocardial lactate levels between the sevoflurane (S) and control
      groups. However, the myocardial ATP level in Group S was significantly higher
      than that in control (17.45 +/- 1.51 vs 15.50 +/- 0.87 : P < 0.01). The
      administration of sevoflurane to the isolated rat heart during pre- and post
      ischemia enhanced metabolic recovery in the postischemic state.

PMID- 15236052
TI  - Effects of halothane and hypoxia on hepatic oxygen metabolism in the dog.
AB  - Hepatic oxygen delivery and consumption were assessed in mongrel dogs receiving
      2MAC of halothane combined with graded hypoxic hypoxemia (21-8% oxygen). Hepatic
      blood flow was measured using electromagnetic flowmetry; hepatic oxygen delivery
      and consumption were calculated from measured hepatic blood flow and oxygen
      content in hepatic arterial, portal venous and hepatic venous blood. In hypoxia
      halothane group, total hepatic blood flow decreased at mild hypoxia (15% O2) from
      control value, but recovered to control level at moderate hypoxia (10% O2), then
      again decreased at 8% O2. Oxygen supply to the liver was decreased with the
      augmentation of hypoxia in hypoxia-halothane and hypoxia-alone groups, and it was
      significantly lower in the hypoxia-halothane group at 15 and 12% O2. Hepatic
      oxygen consumption also decreased from air control values with the increment of
      hypoxia, but there was no significant difference between the groups. Arterial
      ketone body ratio, which indicates mitochondrial energy charge level, decreased
      with the development of hypoxia but there was no significant difference in this
      ratio between the groups. These results show that halothane aggravated oxygen
      supply to the liver at mild to moderate hypoxia (15-12% O2), but did not worsen
      it specifically at more serious hypoxia (10-8% O2) compared with hypoxia alone.
      Hepatic hypoxia itself could not thus be a main cause of halothane
      hepatotoxicity.

PMID- 15236053
TI  - A new closed-system using partially frozen injectate for thermodilution cardiac
      output determinations.
AB  - The FI (partially frozen injectate) system, a new closed-system devised by the
      authors for thermodilution cardiac output determinations, has two major features:
      1) it needs no ice-filled receptacle to keep injectate cold because it uses
      partially frozen injectate, and 2) it can go without monitoring the injectate
      temperatures during the whole process of cardiac output determinations. The
      author evaluated the accuracy and reproducibility of cardiac output
      determinations with the FI system in 10 critically ill patients, as compared with
      another closed-system (which is commercially available) and the standard open
      method. The injectate temperatures in the FI system were also measured in vitro.
      The mean injectate temperature in the FI system was 0.71 +/- 0.26 degrees C and
      80% of the injectate temperatures were lower than 1.0 degrees C. Even when no
      monitoring of injectate temperatures was made, the predicated error in the
      calculated cardiac output resulted as low as 2% with the FI system. The mean
      cardiac output values were not statistically different between the FI system and
      the other two systems.

PMID- 15236054
TI  - Non cardiogenic pulmonary edema as consequence of upper airway obstruction.
AB  - Non cardiogenic pulmonary edema is a rare complication of upper airway
      obstruction. Its etiology is controversial, but probably can be explained by the
      Starling's law, when the large negative intrathoracic pressure generated exceeds
      the intravascular and interstitial pressures, shifting fluids from capillaries to
      interstitium and alveoli. In addition, alteration of capillary permeability
      potentiates fluid migration. We present herein, a case of non cardiogenic
      pulmonary edema following relief of upper airway obstruction in a 14 years old
      girl underwent surgical repair of cleft palate. Cardiogenic pulmonary edema could
      be excluded by a normal CVP, wedge pressure and four chamber echocardiography.
      The edema fluid: plasma protein ratio greater than 0.7 can indicate an increased
      capillary permeability. Mendelson's syndrome could be ruled out by the rapid
      improvement seen and the soft clinical course.

PMID- 15236055
TI  - Prolonged nitrous oxide exposure inhibits settlement of transplanted hemopoietic
      stem cells in murine spleen.
AB  - In order to clarify the mechanism of hemopoietic depression induced by nitrous
      oxide inhalation, effects of prolonged nitrous oxide exposure on the settlement
      of transplanted bone marrow cells were investigated. Mice were continuously
      exposed to mixed gas containing 50% nitrous oxide, 21% oxygen and 29% nitrogen
      for 7 days and then they were irradiated with 850 rads. By the irradiation,
      endogenous pluripotent hemopoietic stem cells (CFU-S) almost disappeared in the
      mice. Normal syngenic murine bone marrow cells were injected intravenously and
      the numbers of CFU-S, which settled in the bone marrow and spleen 2 hr after
      injection, were measured. There was no difference of the numbers of CFU-S settled
      in the bone marrow between nitrous oxide and control gas exposed mice. In
      contrast, the numbers of CFU-S in the spleen of nitrous oxide exposed mice were
      approximately 60% of the control. These results and our previous data suggest
      that hemopoietic inhibitory effects of nitrous oxide in mice are due to a damage
      of splenic hemopoietic microenvironment, that supports the settlement of
      hemopoietic stem cells.

PMID- 15236056
TI  - The cardiovascular effects of naloxone administration after fentanyl anesthesia
      in hypercapnic patients.
AB  - Hemodynamic changes and plasma catecholamine levels after naloxone administration
      were studied in seventeen postoperative patients who received nitrous oxide,
      oxygen, and fentanyl anesthesia combined with epidural block. Group I consisted
      of ten postoperative hypercapnic (PaCO2 = 55.2 +/- 2.4 torr) and group II seven
      postoperative normocapnic patients (PaCO2 = 38.4 +/- 2.1 torr), respectively. In
      group I, naloxone reversal resulted in significant increases in heart rate
      (13.5%), mean arterial pressure (46.6%), systemic vascular resistance (32.1%),
      and rate pressure product (68.8%), whereas mean pulmonary artery pressure and
      pulmonary vascular resistance were significantly decreased. No significant
      hemodynamic changes after naloxone administration were observed in group II.
      There were no significant differences in arterial norepinephrine and epinephrine
      levels either before or after naloxone administration in the both groups. This
      study indicates that the postoperative hypercapnia elicits the cardiovascular
      stimulation after fentanyl reversal by naloxone.

PMID- 15236057
TI  - Preliminary study of epidural nalbuphine in treatment of post operative pain: a
      comparison with equipotent dose of epidural morphine.
AB  - Epidural analgesia was used in 45 patients submitted to upper abdominal surgery.
      In 30 of them 0.15 mg/kg nalbuphine (EN group) was injected and in the remained,
      an equipotent dose of 0.1 mg/kg of preservative free morphine (EM group) was
      used. The patients were observed concerning the severity of pain before and after
      narcotic administration, duration of analgesia, occurrence and severity of side
      effects among them. The severity of pain was stated by the McGill pain score
      (from 0 to 5). Duration of analgesia was defined as the time interval from pain
      relief after narcotic administration until requirement of an additional epidural
      narcotic injection. The adequacy of ventilation was estimated by sequential
      measurements of arterial PCO2. Pain relief was excellent in all patients after
      both narcotics administration. The analgesia time was significantly longer with
      epidural morphine than in the EN patients. Besides drowsiness, the other side
      effects incidence was lower with epidural nalbuphine than with epidural morphine.
      Two patients in the EM group presented clinical respiratory depression, showing a
      significant increase in arterial PCO2. We believe that the lack of respiratory
      depression seen in EN group is a consequence of the rostral diffusion of the
      drug, which reaches high concentrations at the respiratory centers level and a
      direct antagonist action upon them. Our results showed that epidurally
      administered nalbuphine provides a good analgesia, with minor side effects and
      favorably compares with epidural morphine.

PMID- 15236058
TI  - Induced hypotension for surgical repair of congenital dislocation of the hip in
      children.
AB  - The surgical repair of congenital dislocation of the hip was performed under
      normotensive anaesthesia (23 children) and hypotensive anaesthesia (52 children).
      Hypotension was induced with infusion of hypotensive agents such as trimetaphan
      or nitroglycerin during inhalation or neurolept-anaesthesia under careful
      monitoring of blood pressure, haematocrit and electrocardiogram. Blood
      replacement was done to keep hematocrit value above 30%. Blood loss was
      significantly less in hypotensive group (2.53 ml/kg/h) than that in normotensive
      group (4.53 ml/kg/h). Twenty one percent of patients in hypotensive group
      required blood transfusion with the rate of 3.3 ml/kg/h compared with 43% of
      cases in normotensive group with the rate of 4.4 ml/kg/h. Depending upon
      anaesthesia technique blood loss was greater in neuroleptanaesthesia (5.5
      ml/kg/h) than inhalation (2.3 ml/kg/h) or epidural (2.1 ml/kg/h) anaesthesia.
      Urine output and laboratory data for liver and kidney functions were not
      different between normotensive and hypotensive group. The dose of hypotensive
      agents required to produce moderate hypotension for paediatric patients was much
      higher than that for adult. We consider that moderate hypotension is safe
      procedure if employed by well experienced anaesthetist with careful monitoring of
      blood pressure, Hct and ECG. Blood loss and requirement of blood replacement are
      significantly reduced with this technique.

PMID- 15236059
TI  - The influence of ventricular extrasystoles and postextrasystoles on
      cardiovascular dynamics in anesthetized dogs.
AB  - The influence of ventricular extrasystoles and postextrasystoles on
      cardiovascular dynamics were assessed in terms of maximum rate of rise of left
      ventricular pressure (max dP/dt), ascending aortic flow, left ventricular stroke
      volume, and left ventricular end-diastolic transverse dimension in anesthetized
      dogs. A single ventricular extrasystole, two and three consecutive ventricular
      extrasystoles (couplet and triplet) were induced by applying mechanical
      stimulation to the surface of the right ventricule. In any of these ventricular
      extrasystoles, max dP/dt, stroke volume and end-diastolic transverse dimension
      were decreased, compared with those in preceding sinus beats, i.e., pre
      extrasystoles. Over the several postextrasystoles, max dP/dt was increased and
      gradually returned to its control level. This increase in max dP/dt, i.e.,
      postextrasystolic potentiation paralleled an increase in ascending aortic peak
      flow but did not always bring about an increase in stroke volume, even when a
      left ventricular contraction was initiated by a significantly greater end
      diastolic transverse dimension. The postextrasystolic potentiation seems to be
      associated with the Frank-Starling mechanism and does not compensate for the
      decreased in stroke volume elicited by the ventricular extrasystoles. In
      conclusion, not only ventricular extrasystoles per se but also postextrasystoles
      exert the adverse influence on cardiovascular dynamics consecutively.

PMID- 15236060
TI  - Radioallergosorbent test (RAST) for specific IgE antibody to lidocaine, procaine
      and methylparaben.
AB  - Although anaphylactoid reactions to local anesthetics are well known, a
      radioallergosorbent test (RAST) to detect specific drug reagin (IgE) anti-body
      has not been developed. We established RAST for local anesthetics by using
      carboxylic acid derivatives of lidocaine, procaine and methylparaben. Serum
      samples were taken from 100 volunteers who were regarded to be nonallergic to the
      drugs used. Negative RAST values obtained from these volunteers were 1653 +/-
      254(SD) cpm (lidocaine), 2750 +/- 264 cpm (procaine), and 2805 +/- 336 cpm
      (methyl paraben).

PMID- 15236061
TI  - Laboratory evaluation of heat-and-moisture exchangers.
AB  - We conducted a laboratory study on six commercially available heat and moisture
      exchangers in order to determine and compare their water retaining efficiency and
      their contribution to airway resistance. The Gambro-Engstrom Edith Flex device
      was the most desirable of the six devices we evaluated in terms of its water
      retaining efficiency. The NMI Pneumoist 1 and the Siemens Servo Humidifier 153
      units had good water retaining capacity but their higher airflow resistance need
      close monitoring, especially after prolonged clinical use. The Pall HME 15-22 and
      the Portex Humid-Vent 1 devices were also efficient in water retaining capacity.
      The Pall also demonstrated low airflow resistance and the minimum increase in
      airflow resistance after water immersion. The pathogen filtering capacity of the
      Pall should also be considered an additional advantage, especially in infected
      patients. The Terumo Breathaid device performed worst of all six devices, but it
      was still better than no HME at all.

PMID- 15236062
TI  - Neurolysis of celiac plexus and splanchnic nerve under ultrasonographic guidance.

PMID- 15236063
TI  - Clinical assessment of a new neuromuscular transmission monitoring system
      (ACCELOGRAPH--a comparison with the conventional method.

PMID- 15236064
TI  - The best choice of double burst stimulation pattern for manual evaluation of
      neuromuscular transmission.

PMID- 15236065
TI  - Dilution acidosis and an increase of P(A-a)O2 during transurethral resection of
      the prostate.

PMID- 15236066
TI  - Nasotracheal intubation using fiberoptic bronchoscopy in infants and children.

PMID- 15236067
TI  - A new technique of identifying the epidural space "dripping infusion method".
AB  - We developed a new visual technique o identifying the epidural space, using the
      hydrostatic pressure produced by a suspended micro-drip intravenous apparatus.
      When the needle pierces the ligamentum flavum, the resistance to positive
      pressure disappears and the saline in the apparatus flows freely into the
      epidural space. Thus, the entry of the needle point into the epidural space is
      visually confirmed by the appearance of dripping flow in the drip bulb (dripping
      infusion sign). This procedure was clinically evaluated at the thoraco-cervical
      area in 114 patients; the thoracic area in 116; and the lumbar area in 272,
      respectively. In 491 (97.8%) of the patients, the epidural space was identified
      with facility. In the remaining 11 patients (2.2%), a false dripping infusion
      sign appeared at the more superficial site than expected. If the pressure
      waveform in the epidural space is analyzed, the correct positioning of the needle
      can be easily confirmed. We believe that this method is one of the most accurate
      visual methods of identifying the epidural space and useful for teaching the
      epidural blockade to students and residents.

PMID- 15236068
TI  - Increased release of alpha-atrial natriuretic peptide during controlled
      mechanical ventilation with positive end-expiratory pressure in humans.
AB  - The objective of this study was to test the hypothesis that a release of alpha
      artrial natriuretic peptide (ANP) is depressed resulting in the reduction of
      urinary output in patients receiving controlled mechanical ventilation (CMV) with
      positive end-expiratory pressure (PEEP). Five normovolemic patients with no
      apparent cardiac, renal, endocrine, or pulmonary dysfunctions were included in
      this study. After the patients were mechanically ventilated using a volume-cycled
      ventilator with zero cmH(2)O PEEP for one hour, hemodynamic variables were
      measured. Urine and blood samples were collected after the measurements. Plasma
      alpha-ANP levels were determined on blood samples taken from radial artery using
      specific radioimmunoassay. Then PEEP levels were changed to 5, 10, 15 and,
      finally, 0 cmH(2)O in four consecutive one-hour periods. At the end of each
      period, the measurements and collection of the samples were repeated. With
      increasing levels of PEEP, central venous pressure (CVP), pulmonary artery wedge
      pressure (PAWP), and heart rate were pressure-dependently increased. On the other
      hand, cardiac output and urinary output were decreased. Plasma levels of alpha
      ANP were also increased by the institution of PEEP. These changes occurred in a
      pressure-dependent fashion. Urinary sodium excretion, potassium excretion,
      fractional excretion of sodium and free water clearance remained unchanged. It is
      concluded that a release of alpha-ANP was augmented rather than depressed with
      PEEP. This suggests that a decrease in urinary excretion in patients with PEEP
      may not be due to a reduced release of alpha-ANP.

PMID- 15236069
TI  - To-and-for extracorporeal lung assist (ECLA) through a single catheter-in
      premature goats as an experimental model of infant respiratory Insufficiency.
AB  - A new to-and-fro V-V bypass extracorporeal lung assist (ECLA) through a single
      catheter as a blood access was investigated for its efficacy on six premature
      goats delivered by Cesarean section at a gestational age of 118 approximately 139
      days as an experimental model of infant respiratory insufficiency, then applied
      to a human premature infant suffering from life threatening barotrauma that had
      developed from mechanical pulmonary ventilation. The extracorporeal bypass flow
      and the gas flow to the artificial membrane lung were controlled to keep Pa(O)(2)
      above 40 mmHg and Pa(CO)(2) within normal limits. The neonate's own lungs were
      treated with a continuous positive airway pressure of 5 approximately 12 cmH(2)O,
      apneic oxygenation or IMV. Two goats weighing 1250 g and 700 g died 2
      approximately 2.5 hours after birth from severe circulatory distress. However,
      the other four neonates which were heavier than 2000 g, were successfully weaned
      from ECLA, and three of these could be weaned from mechanical ventilation as
      well. A human infant also survived and was weaned from ECLA on the third
      day.(Tanoue T, Terasaki H, Sadanaga M et al.: To-and-fro extracorporeal lung
      assist (ECLA) through a single catheter-in premature goats as an experimental
      model of infant respiratory insufficiency.

PMID- 15236070
TI  - Excretion of trifluoroacetic acid as a metabolite of halothane in digestive
      juices.
AB  - The excretion of trifluoroacetic acid (TFAA) in bile, saliva and gastric juice of
      two groups of guinea pigs with bile fistulae was measured by ion-chromatography
      during inhalation of halothane (0.25% and 1.0%) for two hours and after
      inhalation of halothane. In another two groups without bile fistulae, excretion
      of TFAA was measured in saliva and gastric juice during and after inhalation of
      same concentrations of halothane.The excretion of TFAA increased with time and
      showed the highest concentrations in the saliva. The highest excretion rate and
      cumulative amounts of excreted TFAA were observed in bile. The cumulative amounts
      of TFAA excreted into the bile, saliva and gastric juice was 4.85 +/- 1.87 micro
      mol, 0.89 +/- 0.62 micro mol, 0.11 +/- 0.06 micro mol, respectively, after
      inhalation of 0.25% halothane and 5.36+/- 2.29 micro mol, 1.50 +/- 0.59 micro
      mol, 0.25 +/- 0.19 micro mol, respectively, after inhalation of 1.0% halothane.
      The excretion of TFAA in bile and saliva was saturated after inhalation of the
      higher concentration of halothane. The excretion of TFAA into the gastric juice
      was higher with 1.0% concentration of halothane and in animals without bile
      fistulae. We concluded that TFAA a metabolite of halothane is excreted not only
      in bile but also in saliva and gastric juice. Biotransformation of halothane in
      salivary glands seems very likely. A small amount of TFAA excreted in bile enters
      the enterohepatic circulation. The excretion of TFAA in digestive juice seems to
      be controlled by a rate-limiting mechanism.

PMID- 15236071
TI  - Measurement of airway resistance in anesthetized and paralyzed subjects: proposal
      for evaluation of K1 values.
AB  - The effects of lung volume and respiratory airflow on airway resistance were
      studied in five anesthetized and paralyzed patients. Airway resistance measured
      during the inspiratory phase with intermittent constant airflow inflations
      decreased in inverse correlationship to increases in lung volume. Airway
      resistance measured during the expiratory phase with an airway interruption
      technique, on the other hand, increased with a linear relationship to the
      expiratory airflow as expressed by a function of Y = K(1) + K(2)X. K(1),
      calculated from the values of airway resistance corresponding to three different
      airflows, was unaffected by intentional expiratory resistance loading. Thus,
      simultaneously with the measurement of airway resistance by this method,
      expiratory gas sampling with a Douglas bag can be done if necessary. Since the
      K(2) value of the endotracheal tube used in this study (Portex((R)) I.D. 8 mm,
      length 26 cm) was quite high (5.0 cmH(2)O.1(-2).sec(2)), depending on the
      airflow, the presence of the endotracheal tube strongly affected the measurement
      of airway resistance during general anesthesia. K(1) measured by the above
      method, however, may be considered as the best way to evaluate the lower airway
      resistance independent of either lung volume or expiratory airflow.

PMID- 15236072
TI  - Cardiovascular interaction between sevoflurane and nicardipine in open chest
      dogs.
AB  - Cardiovascular interaction between nicardipine and sevoflurane was examined in
      dogs and compared with nicardipine-thiopental interaction and nicardipine
      halothane interaction. The bolus intravenous injection of nicardipine at dosages
      of 15 micro g/kg and 30 micro g/kg under sevoflurane anesthesia produced
      transient decreases in blood pressure, systemic vascular resistance, left
      ventricular pressure, left ventricular (dp)/(dt) and -(dp)/(dt), and a slight
      increase in cardiac output. The degrees of these changes were almost identical to
      those under thiopental or halothane anesthesia. Left and right atrial pressure,
      pulmonary arterial pressure, pulmonary vascular resistance were not changed by
      nicardipine under any of the three anesthetics. These results suggest that the
      cardiovascular interaction of nicardipine and sevoflurane is additive and similar
      to that of nicardipine and halothane and that the cardiovascular changes induced
      by nicardipine are not modified by the presence of anesthetics.

PMID- 15236073
TI  - Variation in serum ionized calcium on cardiopulmonary resuscitation.
AB  - Changes in serum ionized calcium (Ca(++)) levels during cardiopulmonary
      resuscitation (CPR) and before and after CaCl(2) administration have been
      examined and investigated in 30 patients with cardiopulmonary arrest on arrival
      (dead on arrival patients) when a significant negative correlation was found to
      exist between the transportation time and aCa(++), as the aCa(++) level decreased
      with an increase in the transportation time. Upon arrival, the pH had fallen due
      to acidosis so that aCa(++) and cCa(++) levels were virtually normal. After
      admission, the pH rose as a result of CPR, resulting in a significant drop in
      both Ca(++) levels, so that in most cases resuscitation was not possible. Those
      successfully resuscitated took over 60 min to return to normal Ca(++) levels.
      Administration of approximately 6.6 mg/kg of CaCl(2) led to significant increases
      in aCa(++) and cCa(++) to essentially normal levels, even with some patients
      recording extremely elevated Ca levels, even with some patients recording
      extremely elevated Ca levels. However, the success rate of resuscitation was not
      found to show any significant difference according to whether CaCl(2) had or had
      not been administrated.Thus, it is felt necessary to re-examine the use of
      calcium chloride on CPR.

PMID- 15236074
TI  - Salivary excretion of trifluoroacetic acid (TFAA) after halothane anesthesia.
AB  - Trifluoroacetic acid (TFAA) in the saliva, blood and urine after halothane
      anesthesia was determined by ionchromatography in surgical patients. The mean
      salivary concentration of TFAA was 1115.5 +/- 516.2 micro M on the 1st, 732.4 +/-
      543.9 micro M on the 3rd and 406.6 +/- 258.7 micro M on the 7th post-operative
      day. The mean serum concentration of TFAA was 390.1 +/- 115.7 micro M on the 1st,
      220.8 +/- 73.2 micro M on the 3rd and 133.8 +/- 84.8 micro M on the 7th post
      operative day. The concentration of TFAA in saliva was approximately three times
      as high as that in the blood, but their time courses were almost parallel. The
      excretion of TFAA in urine changed in a similar manner. It was concluded from the
      findings that the salivary gland plays a role as one of the routes for the
      elimination of TFAA.

PMID- 15236075
TI  - Wakefulness during the induction with high-dose fentanyl and oxygen anesthesia.
AB  - The purpose of this study was to investigate the state of wakefulness during the
      induction of anesthesia with high-dose fentanyl using the isolated forearm
      technique. Ten patients scheduled for elective cardiovascular surgery were
      premedicated with morphine (0.15 mg/kg) and scoploamine (0.3-0.4 mg)
      intramuscularly one hour before induction. The induction of anesthesia was
      performed by intravenous administration of 100 micro g/kg of fentanyl in 15 min
      or over. The pneumatic tourniquet applied on the left upper arm was inflated to
      220-240 mmHg after 10 micro g/kg of fentanyl was given and then pancuronium was
      administered. Verbal commands were given to the patient after 25, 50, 75 and 100
      micro g/kg of fentanyl was administered. Eight patients out of 10 responded to
      the verbal commands after administration of 25 micro g/kg of fentanyl. Six
      patients also responded after administration of 100 micro g/kg of fentanyl and
      diazepam 5 mg was given to prevent tachycardia and rigidity during endotracheal
      intubation. Muscle rigidity and tachycardia were noticed in three and four
      patients respectively. These complications disappeared by diazepam
      administration. It was noted that wakefulness frequently occurred during the
      induction by high-dose fentanyl and oxygen anesthesia. To prevent such
      wakefulness therefore, it is necessary to use anesthetic supplements which do not
      cause cardiovascular depression.

PMID- 15236076
TI  - Phrenic nerve and vagal nerve activities during differential lung ventilation in
      cats.
AB  - The effect of differential lung ventilation (DLV) on afferent vagal and efferent
      phrenic nerve activities was studied in urethane anesthetized cats. One
      endotracheal tube was inserted into the left bronchus to ventilate its side lung.
      Another tube was inserted until its tip reached about 1 cm above the carina to
      ventilate the right lung. Using two respirators, each lung was ventilated
      independently. Using hooked silver electrodes, the vagal and phrenic nerve
      activities were recorded. The afferent vagal nerve was activated in concurrence
      with lung inflation at any ventilation rate. The right and left vagal nerves were
      activated by right and left lung ventilation, respectively. On the other hand,
      the right and left efferent phrenic nerves were synchronized, whether the
      ventilation was discussed or ventilation was achieved by right or left one lung
      ventilation or even by asynchronous DLV. The phrenic nerve activity was
      surpressed by one-lung, right or left, ventilation independently, so that the
      rhythm of the phrenic nerve was disturbed by asynchronous DLV. From these
      results, to reduce the stress of patients during asychronous DLV, it was
      considered that patients need heavier sedation than a usual mechanical
      ventilatory support.

PMID- 15236077
TI  - Acute respiratory failure induced by mechanical pulmonary ventilation at a peak
      inspiratory pressure of 40 cmH2O.
AB  - The effects of high pressure mechanical pulmonary ventilation at a peak
      inspiratory pressure of 40 cmH(2)O were studied on the lungs of healthy newborn
      pigs (14-21 days after birth). Forty percent oxygen in nitrogen was used for
      ventilation to prevent oxygen intoxication. The control group (6 pigs) was
      ventilated for 48 hours at a peak inspiratory pressure less than 18 cmH(2)O and a
      PEEP of 3-5 cmH(2)O with a normal tidal volume, and a respiratory rate of 20
      times/min. The control group showed few deleterious changes in the lungs for 48
      hours. Eleven newborn pigs were ventilated at a peak inspiratory pressure of 40
      cmH(2)O with a PEEP of 3-5 cmH(2)O and a respiratory rate of 20 times/min. To
      avoid respiratory alkalosis, a dead space was placed in the respiratory circuit,
      and normocarbia was maintained by adjusting dead space volume. In all cases in
      the latter group, severe pulmonary impairments, such as abnormal chest
      roentgenograms, hypoxemia, decreased total static lung compliance, high incidence
      of pneumothorax, congestive atelectasis, and increased lung weight were found
      within 48 hours of ventilation. When the pulmonary impairments became manifest, 6
      of the 11 newborn pigs were switched to the conventional medical and ventilatory
      therapies for 3-6 days. However, all of them became ventilator dependent, and
      severe lung pathology was found at autopsy. These pulmonary insults by high
      pressure mechanical pulmonary ventilation could be occurring not infrequently in
      the respiratory management of patients with respiratory failure.

PMID- 15236078
TI  - The effect of ulinastatin on reduced nerve conduction velocity and blood
      pressure.
AB  - Application of a pneumatic tourniquet in orthopedic surgery is sometimes followed
      by hypotension and paralysis. Seventy-five patients scheduled for knee joint
      surgery were examined to evaluate the effects of ulinastatin on changes in blood
      pressure, venous pH and motor nerve conduction by pneumatic tourniquet
      application above the knee joint. In fifty-five of the patients, the femoral vein
      of the operating side was cannulated with a catheter to obtain venous blood
      samples before and after tourniquet application. 300,000 Unit of ulinastatin
      (UST) was administered intravenously before inflation of the tourniquet in 10
      patients. In the other sixteen patients, the motor nerve conduction velocity
      (MNCV) of the peroneal nerve was measured before inflation and after release of
      the tourniquet. In the UST-free group, the reduced blood pressure and pH
      persisted for more than 15 min, while in the UST-treated group, the reduced blood
      pressure returned to the normal leven in 15 min. In the control group, femoral
      venous P(O)(2) continued to increase after 10 min, but that in the UST-treated
      group returned to the normal range. Tourniquet application significantly reduced
      peroneal MNCV. Pre-and post-treatment with UST significantly lessened the
      reduction of MNCV induced by the tourniquet. It is concluded that UST may have
      protective and therapeutic effects on ischemic nerve injury, induced by the
      application of a turniquet.

PMID- 15236079
TI  - Negative inotropic effects of ATP on the isometric contractions of isolated rat
      heart muscle.
AB  - The effects of ATP on the isometric contractions of isolated rat left ventricular
      papillary muscle were studied. Exogenously administered ATP had an immediate
      onset, an abrupt response, progressive recovery and produced dose-related
      depression in the peak developed tension, maximum rate of tension development and
      relaxation, which were statistically significant. There were no significant
      changes in the resting tension, time to peak tension and relaxation time, except
      for a significantly prolonged relaxation time at the highest concentration of
      ATP. In the studies of interactions of ATP and either epinephrine or Ca(++), we
      observed that ATP seemed to interfere with the inotropic effect of epinephrine,
      while Ca(++) antagonized the negative inotropic action of ATP. We conclude that
      the site of negative inotropic action of ATP is most likely on the cell membrane,
      where ATP interferes with Ca(++) flux, and that ATP interferes with the positive
      inotropic action of epinephrine.

PMID- 15236080
TI  - The distance from the skin to the epidural space.
AB  - To determine whether there is any systemic relationship between the distance from
      the skin to the epidural space and physical constitution, the distance from the
      skin to the epidural space was measured in 1007 epidural punctures. The distance
      from the skin to the epidural space in male was greater than that in female ( P
      << 0.001). However, the analysis of the distance from the skin to the epidural
      space of the selected patients who had both a weight of 50-60 kg and a height of
      1.5-1.7 m indicated no statistical difference between male and female. The best
      correlation was found between the distance from the skin to the epidural space
      and body weight. The correlation between the distance from the skin to the
      epidural space and height was less striking. Ninety-five percent of the patients
      who received epidural puncture at the thoraco-cervical area (C7-T2) had a
      distance to the epidural space of 4.0-6.9 cm; 87% at the lower-thoracic area (T8
      T10), 4.0-6.9 cm; 93% at the thoraco-lumbar area (T12-L2), 3.0-4.9 cm; 85% at the
      mid-lumbar area (L2-L4), 3.0-4.9 cm. These results may be useful for young
      anesthesiologists to master epidural block safely and efficiently.

PMID- 15236081
TI  - Positive inotropic and chronotropic effects of pancuronium and vecuronium in the
      canine blood-pefused papillary muscle and sinoatrial node preparations.
AB  - The positive inotropic and chronotropic potencies of pancuronium (Pc) and
      vecuronium (Vc) were compared with developed tension of the isolated papillary
      muscle (DT) and sinoatrial rate of the sinoatrial node preparation (SAR). Both Pc
      and Vc caused dose-dependent positive inotropic and chronotropic effects. Pc
      showed much more potent effect than Vc on DT (0.1, 0.3 mg; P << 0.05) or SAR
      (0.03, 0.1, 0.3 mg; P << 0.05). DT and SAR were increased by Pc and Vc, and the
      increase in DT was inhibited by propranolol or tetrodotoxin. These results
      suggest that the cardiac effects of Pc or Vc may be mediated by release of
      norepinephrine from the synpathetic nerve endings.

PMID- 15236082
TI  - Preservation of baroreflex control of vascular resistance under ketamine
      anesthesia in rats.
AB  - The aim of this study was to examine the effects of ketamine and pentobarbital on
      the baroreceptor reflex control of vascular resistance in rats. The gains of
      baroreflex were assessed by relating changes in arterial pressure to changes in
      hindlimb perfusion pressure, using an extracorporeal perfusion circuit with a
      delay system. Reflex-induced vasodilation or vasoconstriction in response to a
      rise or a fall in arterial pressure were elicited by injections of phenylephrine
      or nitroprusside, respectively. The gains of baroreflex were not altered by
      ketamine 1 and 5 mg/kg (i.v.), whereas those were depressed by pentobarbital 5
      mg/kg (i.v.). The results suggest that ketamine preserves the baroreflex control
      of vascular resistance and pentobarbital depresses it. The preservation of the
      baroreflex control of vascular resistance may be advantageous for patients with
      hypovolemia to sustain the blood pressure.

PMID- 15236083
TI  - Quantitative determination of atracurium in human plasma using high-performance
      liquid chromatography.
AB  - The authors have established a new method for extraction and determination of
      atracurium in human plasma that employs a reversed phase high-performance liquid
      chromatography (HPLC). This method made use of a fluorescent spectrophotometer at
      an excitation wavelength of 240 nm and an emission wavelength of 310 nm. The
      mobile phase was made of a phosphate buffer, distilled water and acetonitrile
      (20V : 30V : 50V). The analytical column used was a Little Champ C(18). In a Bond
      Elute C(18) extraction column, which had been prewashed with a phosphate buffer
      and a 50% methanol solution, atracurium was extracted from acidified plasma
      samples using a mixture of methanol and phosphate buffer. A standard curve was
      prepared by the internal standard method using metocurine. A high linear
      correlation between atracurium concentration and the ratio of the atracurium peak
      height to the metocurine peak height was observed (r = 0.9994). The lowest
      threshold for detection of atracurium was 15 ng/ml. When the plasma
      concentrations of atracurium were determined in 2 clinical cases, t(1/2Alpha) was
      2.10 and 1.73 min and t(1/2Beta) was 15.57 and 21.57 min, respectively. These
      results indicate that this method of extraction and determination is appropriate
      for studying the pharmacokinetics of atracurium because it allows a high
      reproducibility, and provides an extremely accurate, simple and quick analysis.

PMID- 15236084
TI  - Effects of halothane and calcium entry blockers on atrioventricular conduction-a
      comparative study of verapamil, diltiazem, and nifedipine.
AB  - The effects of halothane on AV nodal function were evaluated in dogs with
      verapamil, diltiazem, or nifedipine during atrial pacing using the technique of
      His-bundle electrocardiography. Fifty-one mongrel dogs were divided into six
      groups. Anesthesia was induced with ketamine 100 mg im. and thiamylal 25 mg/kg
      iv. The animals were intubated and mechanically ventilated at normocapneic
      levels. Anesthesia was maintained with 50% nitrous-oxide in oxygen with
      pancuronium 2 mg im. Dogs in groups I, III, and V were anesthetized with 0.8%
      halothane and 50% nitrous-oxide in oxygen. We observed interactions between
      halothane and intravenous administration of either verapamil 0.1 mg/kg, diltiazem
      0.15 mg/kg, or nifedipine 0.01 mg/kg respectively. Dogs in groups II, IV, and VI
      were administered either verapamil, diltiazem, or nifedipine iv without
      halothane. There were prolongations of sinus cycle length (SCL) (414 +/- 10 to
      542 +/- 19 msec.), atrium-His (AH) interval (73 +/- 3 to 97 +/- 5 msec.), and
      functional refractory period (FRP) of the AV-node (227 +/- 5 to 260 +/- 5 msec.)
      in halothane anesthesia in groups I, III, and V. There were more prolongations of
      these variables after iv administration of verapamil (SCL; 617 +/- 35, AH; 118 +/
      7, FRP of the AV node; 311 +/- 4) and diltiazem (SCL; 554 +/- 19, AH; 118 +/-
      12, FRP of the AV node; 283 +/- 12) but no prolongations after nifedipine (SCL;
      533 +/- 19, AH; 99 +/- 8, FRP of the AV node; 272 +/- 9). Comparing effects of
      calcium entry blockers with and without halothane in groups I and II, III and IV,
      or V and VI, there were additive depressing effects of halothane with either
      verapamil or diltiazem on AV nodal function. And there is a difference between
      the effects of nifedipine on SCL with and without halothane.

PMID- 15236085
TI  - Effects of sevoflurane on cardiovascular dynamics, coronary circulation and
      myocardial metabolism in dogs.
AB  - The effects of 2.5% and 5% of sevoflurane anesthesia on hemodynamics and
      myocardial metabolism were studied in pentobarbital-pancuronium anesthetized
      dogs. The interaction between nicardipine and 2.5% sevoflurane was also examined.
      Sevoflurane produced dose-dependent ( P << 0.05 to P << 0.01) decreases in
      systolic arterial pressure (SAP), heart rate (HR), cardiac index (CI), left
      ventricular minute work index (LVMWI), maximum rate of rise of left ventricular
      pressure (LV dP/dt), the time constant of fall in isovolumic left ventricular
      pressure (T) and systemic vascular resistance (SVR), whereas stroke volume index
      (SVI) and left ventricular end-diastolic pressure (LVEDP) remained unchanged.
      Central venous pressure (CVP) was significantly ( P << 0.05) increased at 5%.
      Myocardial oxygen consumption (MV(O)(2)), and myocardial lactate extraction ratio
      (ML ext) were decreased in a dose-dependent manner ( P << 0.05). Myocardial
      oxygen extraction ratio (M(O)(2) ext) was significantly ( P << 0.01) decreased at
      5%. The ratio of the left ventricular minute work index to myocardial oxygen
      consumption (LVMWI/MV(O)(2)), i.e., left ventricular efficiency was significantly
      decreased only at 5% ( P << 0.05). Coronary sinus blood flow (CSBF) was
      significantly ( P << 0.05) decreased only at 2.5% sevoflurane and coronary
      vascular resistance (CVR) was significantly ( P << 0.01) decreased only at 5%
      sevoflurane. The ratio of CSBF to CO (CSBF/CO) showed a tendency to increase as
      sevoflurane concentrations were increased. Nicardipine (0.01 mg.kg(-1))
      administered intravenously under 2.5% sevoflurane caused significant ( P << 0.05
      to P << 0.01) decreases in SAP, HR, LV dP/dt, SVR, and CVR, and increases in CVP,
      SVI, CI, and CSBF ( P << 0.05 to P << 0.01). CSBF/CO remained unchanged.
      MV(O)(2), M(O)(2) ext, and ML ext were significantly ( P << 0.05 to P << 0.01)
      decreased. LVMWI/MV(O)(2) showed a tendency to increase. It is concluded that
      sevoflurane causes a rapidly and easily controlled cardiovascular depression and
      may not have unfavorable effects on coronary circulation and myocardial
      metabolism. Nicardipine exerts a synergistic myocardial depressant effect on
      sevoflurane, in terms of both cardiovascular dynamics and myocardial metabolism.

PMID- 15236086
TI  - Effects of meperidine, pentazocine, bupivacaine and lidocaine in spinal
      anesthesia for cesarean section.

PMID- 15236087
TI  - Extracorporeal lung assist for two cases of severe acute respiratory failure.

PMID- 15236088
TI  - Fluctuation of fractional inspired oxygen concentration caused by misuse of Venti
      voice.

PMID- 15236089
TI  - Pneumomediastinum due to high-frequency jet ventilation in a near-drowned infant.

PMID- 15236090
TI  - Three approaches to pathophysiology of shock.

PMID- 15236091
TI  - The effect of sevoflurane on somatically induced sympathetic reflexes.
AB  - The effects of various inspiratory concentrations of sevoflurane anesthetics on
      the sympathetic reflex responses evoked in the left inferior cardiac nerve branch
      following an electrical stimulation to the ipsilateral superficial peroneal nerve
      were investigated in cats. At a 2.0% inspiratory concentration of sevoflurane,
      two components of the somato-sympathetic reflexes with two different latencies
      were recorded. The early component was due to an activation of myelinated A
      afferent fibers (referred to as the A-reflex), while the late component was due
      to an activation of unmyelinated C afferent fibers (referred to as the C-reflex).
      The increase in the concentration of sevoflurane from 2.0% to 3.0% resulted in
      about 50% attenuation of both the A- and C-reflexes. A further increase in the
      concentration of sevoflurane to 4.0% resulted in further suppression of both
      reflexes.

PMID- 15236092
TI  - [Causes for and consequences of the decline of fertility in Germany].
AB  - The decline in fertility is a world-wide phenomenon. In the past fifty years the
      birth rates have decreased by more than a half in both industrialized and
      developing countries. At the same time, life expectancy has doubled. In the
      lecture, facts and trends in fertility, mortality and migration are analyzed as
      causes of the population dynamics and current population predictions for Germany
      and Europe are presented. These data are then used as the basis for a concise
      survey of the most important conflicts of interest due to demographic factors at
      national and international levels (conflicts of interest between the young and
      old generations, between the new and the old provinces of Germany, between
      immigrants and non-immigrants, between people with children and those without).
      Finally, objectives, instruments, and chances of success of a population
      conscious, interdisciplinary policy are discussed on the basis of international
      comparative analyses.

PMID- 15236093
TI  - [Women with epilepsy planning pregnancy].
AB  - There are many important health issues for women with epilepsy, in particular for
      women of childbearing age. Recent surveys have shown that only a minority of such
      patients received information on important issues concerning pregnancy. Pre
      pregnancy counselling should include information on interactions of antiepileptic
      drugs (AEDs) and oral contraceptives, risk of teratogenicity, use of folic acid,
      the importance of monotherapy with the lowest effective dosage of an AED, and the
      safety of breast feeding as well as other special aspects of epilepsy and
      pregnancy. Planned pregnancy and counselling before conception is crucial. With a
      multidisciplinary approach the majority of pregnancies will have a favourable
      outcome. The article addresses these issues and describes practical
      considerations for the counselling of women with epilepsy who are planning
      pregnancy.

PMID- 15236094
TI  - [Alternatives to hysterectomy: a review].
AB  - Total hysterectomy is considered as gold standard in the treatment of symptomatic
      uterine fibroids in women without reproductive wishes. However an increasing
      number of patients asked for alternatives to hysterectomy. Myomectomy,
      endometrial ablation, hormonal treatment, uterine artery embolization, and
      supracervical hysterectomy may be useful in the treatment uterine fibroids in an
      individual patient.

PMID- 15236095
TI  - [Psychosocial counselling of infertile couples].
AB  - Though, from a psychological point of view, infertile couples appear rarely
      symptomized, some of them do need psychological counselling. Over the last years
      detailed treatment concepts have been developed in the sequel of psychosomatic
      research on fertility disorders in Germany. Counselling strategies, advising
      literature for patients as well as the "Counselling Network for Infertility
      Germany" are presented. Hints at how to conduct counselling and curative
      treatment in the case of infertility are given.

PMID- 15236096
TI  - [Friedrich Wilhelm von Halem and his contributions to the inauguration of the
      thalasso-therapy in Prussia in the 18th century. A medico-historical survey].
AB  - This article is dedicated in remembrance of Friedrich Wilhelm von Halem, a former
      student of the University Frankfurt-on-Oder (Viadrina) in later eighteenth
      century Germany. Friedrich Wilhelm von Halem from Aurich, was the first physician
      in the period of the German Enlightenment, who had introduced the thalasso
      therapy as a part of a new health-conception. His pioneering achievement led to
      the foundation of the first health resort on the german coast of the North-Sea in
      Norderney (East Frisian Islands), May 1797.

PMID- 15236097
TI  - [Forensic aspects in pregnancy].
AB  - Modern pregnancy care requires specific management, constant medical training, as
      well as 24 hour employment of midwives and gynaecologists. But not only medical
      aspects determine such pregnancy care - there are also many juridical problems.
      The author comments on pregnancy care contact, maternity guidelines and the
      guidelines of the scientific advisory council of the professional organisation of
      German doctors regarding prenatal diagnosis. Higher court judgements regarding
      medical duties when treating pregnant patients are cited. An important chapter
      deals with legal liability and damage amount in case of breach of duty. Finally,
      principles of medical information, duty of documentation and other forensic
      aspects of modern pregnancy care are explained.

PMID- 15236098
TI  - [Complementary medicine: phytotherapy and soyaisoflavones as phytoestrogens].
AB  - After a introduction concerning complementary medicine, naturopathy and
      phytotherapy a general view of soy isoflavones as phytoestrogens will be given.
      In german speaking countries the term and topic naturopathy has a tradition of
      150 years regarding theoretical development and practical use among lay people
      and health professionals in European culture. In contrary the term complementary
      medicine has been used for approximately 15 years in englisch speaking countries
      as a kind of collective name for European and Non-European medical cultures and
      traditions. Complementay medicine summarizes a huge variety of cultural, medical
      and qualitywise different medical methods and treatments which can be a
      contribution to conventional medicine. One of the oldest and intensly researched
      fields in European and Non-European complementary medicine is the use of herbal
      drugs (phytotherapy). Soy isoflavones serve as an example to show the differences
      between phytotherapy based on multicompounds and dietary supplements
      (neutraceuticals) based on monosubstances. The differing preparations of soy
      isoflavones are not phytotherapeutic medicine. A review of the experimental and
      clinical data concerning soy isoflavones as phytoestrogens for the prevention of
      cancer, menopausal complaints, osteoporosis or cardiovascular diseases indicates
      that the consumption of food containing phytoestrogens seems to be health
      protective. Yet, the relevance of supplementation of single phytoestrogens for an
      additional health effect is not sufficiently proven.

PMID- 15236099
TI  - [Inhibins and Activin A in hypertensive Disorders of Pregnancy and HELLP
      Syndrome].
AB  - OBJECTIVE: Are serum concentrations of the ovarian glycoproteins inhibin A,
      inhibin B, pro-alpha-C and activin A different in normotensive, chronical
      hypertensive or pregancies complicated by preeclampsia or HELLP-syndrome? What
      are the clinical consequences? METHODS: Serum concentrations of inhibin A,
      inhibin B, pro-alpha-C, and activin A of 99 women (37 normotensive patients, 23
      patients with chronical hypertension, 25 women with preeclampsia and 14 patients
      with HELLP-syndrome) at different stages of pregnancy were determined by high
      specific ELISAS. RESULTS: During pregnancy serum levels of all parameters
      increased continually and fell rapidly within parturition. Activin A and inhibin
      B levels showed significant higher serum concentrations in patients with
      preeclampsia and - even more pronounced - in patients with HELLP-syndrome.
      Normotensive and chronically hypertensive patients were not different.
      CONCLUSION: Activin A and inhibin A appear to be viable candidates as laboratory
      parameters for detection of pregnancy induced hypertension. Maybe furthermore
      both parameters will allow the discrimination between chronic hypertension and
      hypertension induced by pregnancy.

PMID- 15236100
TI  - [Induction of labour at term with misoprostol: an effective, safe and inexpensive
      alternative].
AB  - Misoprostol is a prostaglandin E1 analogue marketed for use in the prevention of
      peptic ulcer disease. It is inexpensive and has few side-effects. Although not
      registered misoprostol has been widely used for obstetric and gynaecologic
      indications, such as induction of labour at term. In our clinic misoprostol has
      been use since April 15, 2003. The data of 70 women, who had been treated with
      misoprostol for induction of labour at term form April 15 to August 15, 2003,
      were analysed retrospectively and compared with the data of those women treated
      with dinoprostin in the same period 2002. The time to active labour was longer
      with dinoprostin compared to misoprostol (19.2 h vs. 15.5 h). Parity did not
      influence the time to active labour. The rate of cesarean sections was lower with
      misoprostol (17.2 vs. 25.8 %). The induction of labour with Misoprostol caused
      costs of 58.80 euro. If dinoprostin had been used, it would have cost 4 368.00
      euro. Although not registered, misoprostol is a safe, effective and inexpensive
      alternative for induction of labour with few side-effects. However, patients
      accept the off-label use.

PMID- 15236101
TI  - [Breast cancer treatment during pregnancy - experiences in the department of
      OB/GYN Grosshadern-Munich and review of international data].
AB  - With an incidence of 1 case in 3 000 to 10 000 pregnancies, breast cancer is the
      second common pregnancy associated malignancy besides cervical cancer. An
      analysis of 12 patients with pregnancy associated breast cancer, treated at the
      University Department of OB/GYN Grosshadern, and a review of the international
      literature is presented. Eight women underwent surgery during pregnancy (four
      radical mastectomies, four breast conserving procedures), four received CMF
      chemotherapy during pregnancy (1 to 4 cycles). Three other patients were treated
      post partum. The tumor stages were advanced (> 2 cm: 10/11; N pos.: 8/11; G3:
      7/11; ER/PR neg.: 5/11). One patient with metastatic breast cancer received
      palliative care only and died 1 week after diagnosis and emergency caesarean
      section in the 31 (st) gestational week. Median overall survival was 41 months
      with six patients dead of breast cancer. One pregnancy was terminated in the 20
      (th) week of gestation by legal abortion, another because of intrauterine death
      in the 24 (th) gestational week. Of the other six pregnancies, four were
      terminated by elective caesarean section and two by induced vaginal delivery. One
      child died with trisomy 18 shortly after birth. The five healthy children (now
      aged 3 to 12 years) showed normal development up to now. The cases show the
      challenge and the opportunities associated with therapy of pregnancy associated
      breast cancer. Utmost attention should be turned to the psychological support of
      the woman and her family.

PMID- 15236102
TI  - [Juvenile gigantomastia. Case report and literature survey].
AB  - A juvenile gigantomastia with wet tender ulceration in a 13-year-old premenarchal
      girl (155 cm, 51 kg) developed in only 6 months. Treatment consisted of a
      bilateral reduction mammoplasty with free transplantation of the areolae and
      nipples and the removal of 4.2 kg of breast tissue. Macroscopically the
      resections consisted of "white and solid" tissue. Histologically a fibrous-cystic
      mastopathia was confirmed. It is thus suggested that the etiology of this disease
      might be related to a local hypersensitivity to estrogen. Mediactions (Tamoxifen)
      are mostly ineffective. The treatment consisted of reduction plasty.

PMID- 15236103
TI  - [Wave front correction: a wrong promise or just a misnomer].

PMID- 15236104
TI  - [The practicality of wavefront correction in ophthalmology].
AB  - BACKGROUND: "Wavefront correction" has become an often used concept in refractive
      surgery, even though it is not always uniquely defined. Clinical results,
      however, are lagging behind the original expectations. METHOD: The physical items
      wavefront error, light ray, ray tracing and refraction error first have to be
      well defined, including demonstration of the applicability of the underlying
      model assumptions. In our simulations optical errors of the eye are expressed in
      three different ways: two-dimensional refraction error maps, error maps of
      optical path lengths, and blurred images on the retina. RESULTS: Optical errors
      are completely correctable only at the locations where they originally occur, i.
      e., corneal errors at the cornea, lens errors in the lens. Correction at another
      localization always introduces new errors. Other than in astronomical telescopes,
      the correction of optical path length errors in the human eye is already limited
      by short time-scale fluctuations of the relevant parameters which are two orders
      of magnitude beyond the tolerable error limits. Approximation of the optical path
      length error by a series expansion (e. g., Zernike polynomials) can induce
      additional errors. CONCLUSION: The worse the optical properties of an eye are,
      the less is the wavefront approach applicable for correction.

PMID- 15236105
TI  - [AS Eddington: Prokrustes and the fisherman--the ambiguous meaning of the word
      significance in biological and medical research].
AB  - BACKGROUND: Statistical significance and biological/medical significance are not
      equivalent and should be distinguished from one another. MATERIALS AND METHODS:
      Pertinent data gleaned from the world literature have been analyzed and
      appraised. RESULTS: A semi-schematic display of the available data facilitates an
      overview of the relevant statistical quantities. CONCLUSIONS: The significance
      level of experimental findings should be gauged in accordance with the clinical
      requirements.

PMID- 15236106
TI  - [Clinical aspects and treatment of immune reactions following penetrating normal
      risk keratoplasty].
AB  - PURPOSE: Endothelial graft rejection is one of the most common causes of graft
      failure following penetrating keratoplasty (PK). The aim of this study was to
      evaluate the incidence, time course and outcome of treatment of graft rejection
      after normal-risk PK and to identify possible risk factors for the recurrence of
      immune reactions and irreversible graft failure. PATIENTS AND METHODS: The study
      included 500 eyes from the prospective Erlanger Normal-risk Keratoplasty Study
      with a mean follow-up of 42 +/- 18 (median 40) months. Indications for PK were
      keratoconus in 48 %, Fuchs' dystrophy in 30 %, secondary bullous keratopathy in
      11 %, non-vascularized corneal scars in 7 % and stromal dystrophies in 4 %.
      Standardized complete ophthalmological examinations were performed on a regular
      basis before, during the acute graft rejection and then regularly in a defined
      examination raster in an cornea out-patient service. RESULTS: During follow-up 29
      eyes (5.6 %) developed an episode of endothelial graft rejection (23 eyes with
      acute diffuse and 6 eyes with chronic focal rejection type). Episodes of
      endothelial graft rejection clustered between 11 and 25 months postoperatively
      (15 from 29, 51.7 %). Most grafts (25 of 29) regained clarity after topical and
      systemic steroid treatment. Only 4 patients showed an irreversible graft failure
      requiring a repeat PK, all of whom had secondary bullous keratopathy as the
      primary indication for PK. Risk factors for irreversible graft failure were pre
      existing anterior synechiae in 3 patients and secondary open angle glaucoma in
      pseudoexfoliation syndrome in one patient. Recurrence of graft rejection was seen
      in 5 patients (all with keratoconus) after a time interval of 8 to 12 months.
      Under very low topical steroid treatment no further recurrence was observed in
      all 5 patients up to 2 years. CONCLUSION: Patients should be followed-up on a
      regular base for longer postoperative periods, since most episodes of graft
      rejection were observed between 1 and 2 years after PK. Development of
      irreversible graft failure was strongly associated with pre-existing anterior
      synechiae and pre-existing glaucoma. Low-dose topical steroid treatment after
      immunological rejection seems to prevent the recurrence of further graft
      rejection.

PMID- 15236107
TI  - [Manual endothelial cell enumeration for transplanted corneas in comparison to
      software controlled, automatic enumeration].
AB  - BACKGROUND: The evaluation of the endothelial cells is the most important
      criterion for assessing human donor corneas. The number, morphology and the
      vitality of the endothelial cells are decisive for the transparency of a cornea.
      The study has the following aim: to verify whether there is any difference
      between the manual and the automatic count of the cells by means of the NAVIS(R)
      system. MATERIAL AND METHODS: Both methods were performed on 57 corneas of 35
      patients. A photo was taken for the manual count by a microscope at 40-fold
      enlargement and was printed for further analysis. A grid was applied to this
      photo and the number of the endothelial cells was projected by a multiplicator to
      one square millimeter. For the automatic evaluation a picture was made with 20
      fold microscopic enlargement; the examiner chose an area to be analysed. There
      the count of the cells was controlled by software and directly projected to one
      square millimetre. This was followed by a manual correction. The measurement data
      were statistically evaluated. RESULTS: No statistically significant difference
      was found between the manual and automatic counts. CONCLUSION: The manual count
      of the endothelial cells can be replaced by software-controlled automatic
      analysis and count.

PMID- 15236108
TI  - [Arteriovenous sheathotomy in venous thrombosis].
AB  - BACKGROUND: The pathogenesis of branch retinal vein occlusion (BRVO) seems to
      differ from that of central retinal vein occlusion (CRVO). Arteriosclerotic and
      anatomic aspects suggest that arteriovenous crossing of vessels may play a
      significant role. New procedures like arteriovenous decompression have been
      proposed to be a suitable form of treatment. PATIENTS AND METHODS: In a clinical
      trial, 12 patients with ischemic BRVO underwent surgical decompression. Strict
      criteria of inclusion were maintained. Arteriovenous sheathotomy (AVS) was
      performed 0.5 - 6 months after retinal vein occlusion. Follow up-time was 3
      months. Visual acuity and incidence of typical complications after RVO were the
      main aspects of interest in the scientific evaluation. RESULTS: After surgical
      AVS, visual acuity increased significantly from logMAR 0.74 (decimal 0.18) to
      0.56 (0.32) in EDTRS charts. Surgical or early complications did not occur during
      the 3-month control period. Improvement of retinal blood flow during angiography
      was demonstrated in 75 % of the patients. In 50 % of the patients all non
      perfusion areas had disappeared. CONCLUSIONS: For patients with retinal vein
      occlusion, AVS seems to be a safe and feasible procedure according to the
      pathogenesis of branch occlusion. Our results suggest that AVS has the potential
      to improve visual acuity while typical complications due to surgery or vein
      occlusion do not occur during the first three months.

PMID- 15236109
TI  - [Comparison of preoperative retinometer values with postoperative visual acuity
      after surgery of epiretinal membranes].
AB  - BACKGROUND: We report about our clinical experience when comparing the
      preoperative retinometer values with the postoperative visual acuity after
      microsurgical excision of epiretinal membranes (ERM). PATIENTS AND METHODS: Pars
      plana vitrectomy with membrane peeling was performed in 56 eyes of 53 patients.
      Preoperatively, we obtained the distant and near visual acuity and the
      retinometer value. Postoperatively, we compared the preoperative retinometer
      value to the best postoperative visual acuity. RESULTS: The preoperative
      retinometer value was in 39 eyes (70 %) equal to the best postoperative distant
      visual acuity (+/- 1 line) and in 34 eyes (61 %) equal to the best near visual
      acuity (+/- 1 line). A difference of + 2 or - 2 lines or more from the
      retinometer value was found in 17 eyes (30 %) for the best postoperative distant
      visual acuity and in 22 eyes (39 %) for the best near visual acuity. 49 eyes
      (87.5 %) had a better visual acuity after pars plana vitrectomy, 6 eyes (10.7 %)
      had equal visual acuities and one eye (1,8 %) was worse than the preoperative
      visual acuity. The average improvement of vision after the operation was + 2.5
      lines for the distant and + 2.4 lines for the near visual acuity. CONCLUSIONS:
      The preoperative retinometer examination is a precise method for obtaining the
      visual acuity of patients selected for pars plana vitrectomy with membrane
      peeling. Uncertain results can be achieved in eyes with very opaque ERM and ERM
      with macular edema.

PMID- 15236110
TI  - [Cataract surgery with implantation of toric silicone lenses for severe
      astigmatism after keratoplasty].
AB  - BACKGROUND: The treatment of high astigmatism after keratoplasty is often not
      possible with glasses or refractive corneal surgery, particularly in patients
      with anisometropia and contact lens incompatibility. METHODS: In 3 patients with
      cataract and high astigmatism after penetrating keratoplasty, phacoemulsification
      was performed via a 4 mm sclerocorneal tunnel incision. A toric silicone lens
      with Z-haptic was implanted in the bag (Type MS 6116 TU, Dr. Schmidt). All
      patients had high anisometropia and contact lens incompatibility. The follow-up
      was ten weeks, uncorrected and corrected visual acuity, corneal and total
      astigmatism were evaluated. RESULTS: A 68-year-old female presented with corneal
      astigmatism of 10 dpt. Keratoplasty was performed two years earlier. After
      implantation of a toric lens (+ 22.5 + 11.0 dpt.) uncorrected visual acuity
      increased from 1/50 to 20/40, corrected visual acuity increased from 20/30 to
      20/25. A 78-year-old male presented with irregular corneal astigmatism of 6.5
      dpt. Keratoplasty was performed 25 years previously. Due to high myopia (corneal
      radii 5.3/5.9 mm), implantation of a toric lens (- 3.0 + 7.0 dpt.) in the bag was
      combined with implantation of a spheric lens (- 6.0 dpt., Type MS 614, Dr.
      Schmidt) in the sulcus. Uncorrected visual acuity increased from light perception
      to 1/20, corrected visual acuity increased to 1/10. An 84-year-old female
      presented with irregular corneal astigmatism of 8.6 dpt. Keratoplasty was
      performed two years earlier. After implantation of a toric lens (+ 16.0 + 11.0
      dpt.) uncorrected visual acuity increased to 20/50, corrected visual acuity
      increased from 20/100 to 20/25. During the follow-up all implanted lenses were
      well-centered and no significant IOL rotation was observed. CONCLUSION:
      Implantation of foldable toric silicone lenses during cataract surgery may
      improve considerably the uncorrected visual acuity by reducing the total
      astigmatism in patients with high astigmatism after keratoplasty. Preoperatively,
      a reliable keratometry is important.

PMID- 15236111
TI  - [Complete occlusion of the frontal capsule after cataract-operation in a patient
      with pseudoexfoliation syndrome--a case report and review of literature].
AB  - BACKGROUND: Pseudoexfoliation syndrome (PEX) is associated with an increased risk
      for the development of capsular fibrosis including capsular phimosis. A complete
      occlusion of the anterior capsular opening is, so far, a rarely reported
      phenomenon. PATIENT: Here we report the case of a 75-year-old female patient who
      suffered from a secondary open-angle glaucoma caused by PEX. Three months after
      an uneventful cataract surgery with capsulorhexis, phakoemulsification and
      implantation of a posterior chamber lens (PMMA) the anterior capsular opening of
      her left eye was completely occluded. RESULTS: The patient reported a slow loss
      of vision (20/40 immediately after cataract surgery to 20/200 at the follow-up
      visit three months later). The examination revealed a complete closure of the
      capsulorhexis with thick, central fibrous material. The diameter of the
      capsulorhexis was extensively diminished. Reopening of the anterior capsular
      opening utilizing a YAG laser was achieved and visual acuity increased to 20/40.
      Additionally, the fibrotic, secondary cataract of the posterior capsule was
      removed, again with a YAG laser, five weeks after the first intervention and, now
      with a free optical axis, the patient's visual acuity increased further to 20/30.
      CONCLUSION: The excessive production of fibrosis and the tendency towards a
      shrinkage of the diameter of the capsulorhexis postoperatively in patients with
      PEX may lead to a complete occlusion of the capsulorhexis. Even in such extreme
      cases, the reopening of the anterior and posterior capsule by a YAG laser is
      possible and, as demonstrated here, leads to a morphologically and functionally
      satisfying result.

PMID- 15236112
TI  - [Relapsing, therapy refractory episcleritis, paraproteinemia and cutaneous
      subcutaneous nodules on arm and hip: manifestations of a necrobiotic
      xanthogranuloma (NXG)].
AB  - BACKGROUND: Necrobiotic xanthogranuloma is a rare granulomatous disease featuring
      nodular, sometimes ulcerating, skin lesions in association with paraproteinemia
      and variable organ disease. Eye involvement manifests itself often as periorbital
      plaque-like infiltrates but also as chronic episcleritis, conjunctivitis,
      keratitis and scleritis. CASE REPORT: A 49-year-old female patient presented to
      our hospital with a seven-year history of relapsing bilateral episcleritis
      refractory to treatment. Her past medical history included an IgG paraproteinemia
      and C4-deficiency of unknown etiology. A year prior to presentation the patient
      had undergone biopsy of a skin nodule on her arm which histologically was
      suspected to be an infectious granuloma. A recurrence of the lesion at the site
      of biopsy together with a new nodule on the hip prompted us to perform further
      histological analyses. RESULTS: The histological specimen displayed numerous
      giant cells of the foreign body and Touton type, some xanthomatous foam cells
      with cholesterol clefts and collagen necrosis, leading to the diagnosis of NXG.
      As part of the disease, serology showed an IgG lambda paraproteinemia, elevated
      cANCA values, a C4 deficiency and a negative rheumatoid factor. No other
      immunological dysfunction was detected. CONCLUSIONS: NXG is a severe multi-system
      disorder that may cause various chronic inflammatory conditions of the eye's
      anterior segment. Its early diagnosis is mandatory as potentially fatal organ
      complications may arise and the association with lymphoproliferative diseases has
      been described. Due to the relative rarity of the disease no binding therapeutic
      regimen exists. Options include alkylating agents in combination with
      corticosteroids, plasmapheresis and subcutaneous interferon alfa-2 b.

PMID- 15236113
TI  - [Angle closure glaucoma in association with relative anterior microphthalmus
      (RAM) after premature birth-retinopathy (ROP)].
AB  - BACKGROUND: The infantile angle-closure glaucoma is a common and well
      characterized complication of retinopathy of prematurity (ROP). Progressive
      shallowing of the anterior chamber by retrolental fibrous masses is mostly
      responsible for the pressure elevation during the first years of life. Apart of
      this pathogenesis, ROP-associated glaucoma is totally different in cases that do
      not manifest until adulthood. Only few cases are described in the literature.
      CASE REPORT: A 36-year-old female patient presented with symptoms of acute
      intraocular pressure (IOP) elevation and fundus results of a cicatricial ROP
      stadium II. Control of IOP was not achieved by systemic and topical drug
      treatment. The biometry showed a relative anterior microphthalmus (RAM) in
      myopia. After peripheral iridectomy, the IOP normalized and remained stable over
      a long-time period. CONCLUSION: Myopia induction after ROP and ROP treatment
      often lead to special anatomical conditions corresponding to the classical
      relative anterior microphthalmus. Shallowing of the anterior chamber and
      development of angle-closure glaucoma increase with age. Thus, a manifestation
      not before the third decade of life was a typical finding in the literature
      review. A detailed recording of history and consideration of the biometric data
      are of importance for diagnosis. Peripheral iridectomy was found to be the
      therapy with the highest success rate. The increase of a pupillary block
      mechanism can prevent further visual loss to the often pre-damaged eyes.
      Consideration of this entity is crucial in unilateral IOP elevation, because an
      increasing prevalence of these patients can be expected due to the increase of
      premature babies since 1970.

PMID- 15236114
TI  - [Unilateral amaurosis as the only focal symptom caused by dissection of the
      common carotid artery].
AB  - BACKGROUND: Central retinal artery occlusion with persistent amaurosis as the
      only focal symptom caused by dissection of the internal carotid artery has
      occasionally been reported. Central retinal artery occlusion due to a common
      carotid artery dissection has been diagnosed only very rarely. CASE REPORT: We
      describe a patient presenting with cervical pain, headache and unilateral
      amaurosis due to a thrombosis of the central retinal artery caused by a common
      carotid artery dissection, as demonstrated on MR imaging. No other neurological
      deficits could be detected. The patient underwent an anticoagulative treatment
      without improvement of his vision, but also without the appearance of further
      neurological symptoms. CONCLUSION: In monocular visual loss combined with
      cervical pain or headache, carotid artery dissection should be considered. Early
      treatment might be of crucial importance for the prevention of a devastating
      hemispheric stroke.

PMID- 15236115
TI  - [Comments on Langmann et al].

PMID- 15236116
TI  - [Job profile of the eyes of police executive power officials].

PMID- 15236117
TI  - [The story of the hypothesis of the participation of the Muller cells in the
      development of idiopathic macular hole].

PMID- 15236118
TI  - [A simple method, for tear production stimulation in dry eye].

PMID- 15236119
TI  - [Ernst Abbe, the founder of modern optics].

PMID- 15236120
TI  - [Evidence based radiology].

PMID- 15236121
TI  - [Turkish as a scientific language].
AB  - In this article, Turkish is evaluated as a science language and the efforts of
      TUBA (Turkish Academy of Sciences) on the subject are mentioned.

PMID- 15236122
TI  - [Biochemical and immunological effects of ionizing radiation in radiology staff
      members].
AB  - PURPOSE: This study aimed to investigate the influence of occupational exposures
      to long term low-dose ionizing radiation on blood biochemistry and immunity
      levels of the radiology staff. MATERIALS AND METHODS: Fifty-one subjects, aged
      between 21-57 years (30.06+/-7.02 years), working in the department of radiology
      were enrolled to this study. Twenty-five subjects (49.1%) were female and 26
      (50.9%) were male. Control group consisted of 40 healthy non-smoking subjects
      aged between 20-60 years (mean 31.5+/-5.75) who had never been exposed to
      radiation; 19 (47.5%) of these were female and 21 (52.5%) male. Venous blood
      samples were obtained from the radiology staff and control group and
      immunological and biochemical analysis of samples were performed. RESULTS: CD4+ T
      lymphocyte ratio, and serum total IgA, IgG, IgM and C3, C4 levels were lower in
      the radiology staff compared to the controls. Serum triglycerides and paraoxonase
      activities were increased in the radiology staff (p<0.05). CONCLUSION: In
      radiology workers exposed to long-term low-dose ionizing radiation, levels of the
      CD4+ T lymphocytes, total immunoglobulins (IgA, IgG, IgM), C3 and C4 levels were
      lower, while serum trygliceride levels and paraoxonase activities were
      significantly higher (p<0.05). IgA and IgM levels of smoker radiology workers
      were significantly lower than non-smoker radiology workers (p<0.05). Since the
      staff members of department of radiology are vulnerable to the side effects in
      parallel to the dose of radiation being exposed, we think that in addition to
      avoiding radiation as much as possible, they should have periodical blood
      biochemistry and immune function tests.

PMID- 15236123
TI  - [Frequency of vascular variations and anomalies accompanying intracranial
      aneurysms].
AB  - PURPOSE: Investigation of the sites of intracranial aneurysms and incidence of
      associated congenital variations or anomalies. MATERIALS AND METHODS: One hundred
      and ninety cerebral angiography examinations that were positive for aneurysm were
      evaluated retrospectively. Fourteen cases with vasospasm were excluded and the
      remaining 176 patients were assessed for the location of the aneurysm and co
      incidental vascular variations and/or anomalies. There were two observers in the
      study, one of whom was an experienced vascular radiologist. RESULTS: The most
      frequent locations of aneurysms were the supraclinoid internal carotid artery
      (32%, n=74), anterior communicating artery (30%, n=68), and middle cerebral
      artery bifurcation (23%, n=52). Twenty-eight patients (17%) had multiple
      aneurysms. Ninety-one (52%) patients had a vascular anomaly or variation.
      Hypoplasia or agenesis of A1 segment of the anterior cerebral artery was found in
      48 patients, an azygous anterior cerebral artery in 1, a frontoorbital artery in
      1, a duplicated middle cerebral artery in 1, early bifurcation of the middle
      cerebral artery in 9, persistent fetal origin of the posterior cerebral artery in
      26, fenestration of P1 segment of posterior cerebral artery in 1, agenesis of P1
      segment of posterior cerebral artery in 1, fenestration of vertebral artery in 1,
      double trunk visualization of superior cerebellar artery in 2 patients.
      CONCLUSION: Due to an increased hemodynamic stress, congenital anomalies of the
      intracranial arteries predispose to the formation of saccular aneurysms. Nomalies
      such as A1 hypoplasia or agenesis, azygous anterior cerebral artery, accessory
      middle cerebral artery and persistent trigeminal artery are detected more
      frequently in patients with cerebral aneurysms compared to the normal population.
      The location of aneurysms and the frequency of arterial variations and anomalies
      in this study correlated well with data found in previous studies.

PMID- 15236124
TI  - [Diffusion-weighted MRI in the differentiation of brain abscesses and necrotic
      tumors].
AB  - PURPOSE: The differential diagnosis between brain abscesses and necrotic tumors
      such as glioblastomas and metastases is often difficult by conventional MRI. The
      goal of our study was to evaluate the ability of the diffusion-weighted (DW) MRI
      to differentiate these lesions from each other. MATERIALS AND METHODS: MRI was
      performed in 19 patients (four abscesses, seven glioblastomas, two anaplastic
      astrocytomas, six metastases). In addition to standard MR sequences, trace DW
      imaging and apparent diffusion coefficient (ADC) maps were performed. ADC values
      were calculated for all lesions. For statistical analysis student t-test was
      used. A p value less than 0.05 indicated a statistically significant difference.
      RESULTS: The central portion of all six metastases and eight of nine high-grade
      gliomas showed unrestricted diffusion, whereas all four abscesses showed
      restricted diffusion (low ADC values) in their cavity. However, restricted
      diffusion also was found in one glioblastoma. The ADC values of abscesses (0.69
      /+0.05 x103 mm2/s) were significantly lower than of 15 malignant necrotic tumors
      (2.39-/+0.63 x 103 mm2/s). The difference between abscess and necrotic tumors was
      statistically significant (p<0.001). CONCLUSION: DW MRI can be used to identify a
      brain abscess and can help to differentiate it from a cystic brain tumor.
      However, restricted water diffusion is not specific and pathognomonic in the
      differential diagnosis between abscesses and necrotic tumors.

PMID- 15236125
TI  - [Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain
      metastases (case report)].
AB  - Intracranial metastases represent 7-17% of all brain tumors. Renal cell
      carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer
      and breast cancer have a propensity for producing hemorrhagic brain metastases.
      Leukemias have also been rarely reported to cause hemorrhagic brain metastases.
      We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia
      presenting with multiple hemorrhagic brain metastases. MRI demonstrated high
      signal intensity lesions on both T1- and T2-weighted images which were
      characteristic for extracellular methemoglobin and consistent with hemorrhagic
      metastases.

PMID- 15236126
TI  - [Pulmonary aspergillosis: variable appearances (pictorial essay)].
AB  - Pulmonary aspergillosis can present in different clinical, pathological and
      radiological forms depending on the patient's immunological status and underlying
      pulmonary disease. Allergic bronchopulmonary aspergillosis, aspergilloma,
      invasive and semi-invasive forms can be recognized. In this article, we review
      the radiological findings of different forms of pulmonary aspergillosis.

PMID- 15236127
TI  - [Spontaneous rupture of mediastinal cystic teratoma (case report)].
AB  - Teratomas are rare tumors in the mediastinum. Benign cystic teratomas of anterior
      mediastinum are rarely complicated by rupture into an adjacent body cavity. Such
      rupture, however, is usually associated with life-threatening complications. We
      present a case with spontaneous rupture of mediastinal cystic teratoma. The
      patient was evaluated with chest radiograph, computed tomography (CT) and
      magnetic resonance imaging (MRI). A complex mass including predominantly cystic
      components was detected in the left anterior mediastinum. After surgery,
      pathologic diagnosis was reported as mature cystic teratoma. High levels of
      amylase and lipase were detected in both the cystic fluid and serum. This finding
      supported the hypothesis of autolysis for the explanation of rupture. In
      addition, carbohydrate antigen (CA) 19-9, CA 125 and carcinoembryonic antigen
      (CEA) levels were high in the cystic fluid.

PMID- 15236128
TI  - [Unenhanced spiral CT in the diagnosis of acute appendicitis].
AB  - PURPOSE: To evaluate the role of unenhanced spiral computed tomography (CT) in
      the work-up of patients with suspicious symptoms of acute appendicitis. MATERIALS
      AND METHODS: Sixty-five patients with suspected acute appendicitis (34 (52%)
      women and 31 (48%) men), were studied with spiral CT without administration of IV
      or oral contrast. From the upper L1 vertebral plate to the superior border of the
      iliac wings, slices of 10 mm collimation with 8 mm/sec table speed were taken,
      and from that level to the acetabular roof level, 5 mm thick slices were obtained
      with a table speed of 5 mm/sec and tube rotation time of 1.5 sec. The diagnosis
      of acute appendicitis was made by seeing a dilated appendix vermiformis greater
      than 6 mm in diameter and/or an appendicolith accompanied by periappendiceal
      inflammatory changes. The findings were compared with surgical and pathological
      results. Those patients who were not operated on were followed-up for 3 months.
      RESULTS: Acute appendicitis was diagnosed in 28 (43%) of the 65 patients. Of the
      28 patients with a CT diagnosis of acute appendicitis, 25 (38%) had acute
      appendicitis proven by surgery and pathology. Twenty-one (32%) patients had a
      normal CT study and 16 (25%) patients had non-appendiceal pathologies. There were
      25 true-positives, 35 true negatives, 3 false positives and 2 false negatives.
      Non-contrast helical CT had a sensitivity of 93%, specificity of 92%, accuracy of
      95%, positive predictive value of 89% and negative predictive value of 95% in the
      diagnosis of acute appendicitis. CONCLUSION: Non-contrast CT is an accurate,
      reliable and efficacious method in the diagnosis of acute appendicitis. It also
      has the advantage of showing other pathologies mimicking the symptoms of acute
      appendicitis.

PMID- 15236129
TI  - [Incidence of left renal vein anomalies in routine abdominal CT scans].
AB  - PURPOSE: To study the appearance and incidence of left renal vein anomalies in
      abdominal CT examinations. MATERIALS AND METHODS: One thousand and three
      abdominal CT examinations were reviewed retrospectively for the presence of left
      renal vein anomalies. Nineteen CT scans were excluded from the study because of
      technical or patient-dependent factors. The course of the left renal vein was
      assessed on the CT slices to detect any anomalies. RESULTS: Left renal vein
      anomaly was detected in 32 (3.2%) of 984 cases. Twenty-three (2.3%) of them were
      a retroaortic and 9 (0.9%) of them were a circumaortic left renal vein.
      CONCLUSION: It is important to detect left renal vein anomalies before
      retroperitoneal surgery or interventional procedures. These anomalies can be
      identified in routine abdominal CT examinations with a careful inspection.

PMID- 15236130
TI  - [Recurrence rate after varicocelectomy in infertile men].
AB  - PURPOSE: To detect the recurrence rate of varicocele in infertile men with
      varicocelectomy. MATERIALS AND METHODS: Twenty of 94 infertile patients with
      varicocelectomy were examined by color Doppler ultrasonography. RESULTS: We found
      60% recurrence of varicocele infertile men with varicocelectomy. The mean time
      after varicocelectomy was five years for the patients with recurrence, and seven
      years for patients without recurrence. CONCLUSION: Doppler sonography is a useful
      imaging modality in the examination of post-varicocelectomy infertile men without
      successful impregnation.

PMID- 15236131
TI  - [Primary appendagitis epiploica: diagnosis and follow-up with CT (case report)].
AB  - Primary appendagitis epiploica is a rare benign self-limiting inflammatory
      condition of the colonic epiploic appendices. It causes acute localized abdominal
      pain thought to be the result of torsion or spontaneous vascular thrombosis of
      epiploic appendices. This is a non-surgical situation that clinically mimics
      other conditions requiring surgery such as acute diverticulitis or appendicitis.
      In this report, CT findings of this rare disease are presented at the stage of
      initial diagnosis and follow-up.

PMID- 15236132
TI  - [Uterine arteriovenous malformation: US, color Doppler US and MRI findings (case
      report)].
AB  - Uterine arteriovenous malformations are rare but life threatening lesions. Sixty
      nine-year old, multiparous, postmenopausal patient complained of intermittent
      vaginal hemorrhage for 4 years. Serum beta-HCG level of the patient who had no
      history of uterine curettage or pelvic operation was normal. Noninvasive
      diagnosis of arteriovenous malformations with congenital or acquired etiology can
      be made by color Doppler ultrasonography and MRI.

PMID- 15236133
TI  - [Primary hepatic actinomycosis: a case of inflammatory pseudotumor (case
      report)].
AB  - Actinomycosis is an uncommon chronic infection in which primary liver involvement
      accounts for 5% of all actinomycotic infections. Abdominal actinomycosis is a
      severe and progressive peritoneal infection due to an anaerobic gram-positive
      bacterium, Actinomyces israelii. The presence of a long-standing intrauterine
      device (IUD) is a well-known risk factor in young women. Although hepatic lesions
      are present in 15% of cases of abdominal actinomycotic infection, liver
      involvement in the majority of these cases is attributable to metastatic spread
      from other evident intraabdominal sites. Hepatic actinomycosis presents most
      commonly as a single abscess. However, hepatic actinomycosis can closely mimic a
      malignant tumor on clinical and radiological examination. Such lesions have been
      termed inflammatory pseudotumors. Tissue specimens for microscopic examination
      are necessary for diagnosis. We report a rare case of inflammatory pseudotumor of
      the liver caused by actinomycotic infection.

PMID- 15236134
TI  - [Omental infarction: CT findings (case report)].
AB  - Omental infarction, the end result of impaired perfusion of the greater omentum,
      is an uncommon cause of acute abdominal pain. Because its clinical symptoms are
      nonspecific, it is usually confused with more common conditions such as
      appendicitis or cholecystitis. Consequently, the diagnosis is generally made
      intraoperatively. However, computed tomography shows characteristic findings and
      allows a reliable preoperative diagnosis, preventing unnecessary laparotomy. We
      report two cases of omental infarction, and describe typical CT findings of this
      rare entitiy.

PMID- 15236135
TI  - [Doppler ultrasound diagnosis of lower extremity deep vein insufficiency:
      Valsalva maneuver or pneumatic cuff?].
AB  - PURPOSE: To compare the efficacy of Valsalva maneuver and pneumatic compression
      techniques in detecting lower extremity deep venous and saphenofemoral
      insufficiency. MATERIALS AND METHODS: Eighty-one extremities evaluated in 43
      patients who had undergone Doppler ultrasound examination of the lower extremity
      venous system were included in the study. Valsalva maneuver and pneumatic cuff
      techniques were used to elicit reflux in the standing position. Reflux was
      investigated with spectral Doppler in the superficial femoral vein, popliteal
      vein, the proximal segment of the great saphenous vein close to its junction with
      the femoral vein and in its caudal segment at the medial aspect of the knee. The
      same measurements were repeated after rapid deflation of the pneumatic cuff,
      which was applied to the calf and was initially inflated to 200 mmHg. Retrograde
      flow exceeding 1000 msec was regarded as insufficiency. The results of the two
      techniques at each venous segment were compared with the McNemar test. RESULTS:
      Deep venous and/or saphenofemoral insufficiency were detected in 61 of the 81
      extremities. The cuff deflation technique was superior at the popliteal vein and
      caudal segment of the great saphenous vein. The Valsalva maneuver was superior at
      the superficial femoral vein. The statistical results did not change when the
      McNemar test was repeated for reflux exceeding 2000 msec. CONCLUSION: Combined
      application of Valsalva maneuver and pneumatic cuff techniques will lead to more
      accurate evaluation and increased detection of lower extremity venous
      insufficiency.

PMID- 15236136
TI  - [Center specific duplex Doppler threshold values in carotid artery stenosis].
AB  - PURPOSE: The traditional categorizations of color Doppler ultrasonography (CDUS)
      used for grading internal carotid artery stenosis are not consistent with the
      multicenter controlled randomized studies of carotid artery endarterectomy. The
      purpose of this study was to determine duplex Doppler threshold values specific
      to our center for classification of critical internal carotid artery stenosis
      which is determined according to the results obtained from multi-center clinical
      studies. MATERIALS AND METHODS: CDUS and digital subtraction angiography
      examinations were performed in 147 patients who were considered suitable for
      carotid endarterectomy. Using the values of peak systolic velocity (PSV), end
      diastolic velocity and peak systolic velocity ratio (PSV ICA/CCA), the optimum
      duplex Doppler threshold values were determined for internal artery carotid
      stenoses by ROC (receiver operating characteristics) analysis. RESULTS: The most
      accurate threshold levels for detection of ICA stenoses were found to be a PSV
      133 cm/s for 50-99% stenosis, PSV ICA/CCA 2.6 for 60-99% stenosis and PSV ICA/CCA
      3.6 for 70-99% stenosis. Sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy estimated using optimal duplex criteria
      for identification of ICA stenoses were 88%, 85% 78%, 91%, 86% for 50-69%, 94%,
      87%, 71%, 98%, 89% for 60-99% stenosis, 92%, 92%, 65%, 99%, 92% for 70-99%
      stenosis, respectively. CONCLUSION: The duplex criteria established in our center
      have high accuracy. Every center should establish its own duplex criteria for the
      diagnosis of carotid artery stenosis.

PMID- 15236137
TI  - [Evaluation of rhinorrhea by computed tomography cisternography (letter to the
      editor)(Re: Tani Girisim Radyol. 2003 Sep;9(3):327-32)].

PMID- 15236138
TI  - Impact of exclusion criteria on case mix, outcome, and length of stay for the
      severity of disease scoring methods in common use in critical care.
AB  - OBJECTIVE: To identify the exclusion criteria for the major severity of disease
      scoring methods in critical care and to investigate the impact of the exclusion
      criteria on the case mix, outcomes and length of stay for admissions to intensive
      care units (ICUs) in England, Wales and Northern Ireland. DESIGN: Cohort study
      analysis of prospectively collected data. SETTING: 127 adult, general (mixed
      medical/surgical) ICUs in England, Wales and Northern Ireland. PATIENTS: 120,503
      admissions between 1995 and 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Thirteen different exclusion criteria were identified from the original
      methodological/validation papers and data collection manuals for APACHE II,
      APACHE III, SAPS II and MPM II. Application of the original exclusion criteria
      for the four, major severity of disease scoring methods resulted in exclusion of
      between 11.5% and 14.6% of admissions. Hospital mortality for the overall cohort
      was 29.0% but ranged from 4.7% to 50.1% among those groups excluded. After
      application of the exclusion criteria for each scoring method, there was little
      difference in overall hospital mortality or median ICU and hospital length of
      stay for the included admissions when compared with the original cohort. At the
      level of individual ICUs, there were differences in hospital mortality before and
      after exclusions-minimum -3.1% to maximum 9.5% (APACHE II), minimum -2.8% to
      maximum 9.4% (APACHE III), minimum -3.1% to maximum 16.1% (SAPS II) and minimum 
      3.1% to maximum 16.5% (MPM II). The mean difference across individual ICUs was 
      0.5 % (95% CI -0.7% to -0.2%) for APACHE II, -0.2% (95% CI -0.2% to 0.1%) for
      APACHE III, 2.0% (95% CI 1.7% to 2.4%) for SAPS II and 2.1% (95% CI 1.7% to 2.5%)
      for MPM II. SAPS II and MPM II showed systematic variation. A survey of the
      literature found wide variation in the exclusion criteria reported in subsequent,
      published research using a single severity of disease scoring method (APACHE II).
      CONCLUSIONS: Exclusion criteria used in critical care research are often ill
      defined and poorly reported. More attention to the choice of exclusion criteria
      and their effect on the reported results is essential. We hope this study will
      raise the need for both better reporting of exclusion criteria applied in studies
      and promote the need for a common set of explicit exclusion criteria for these
      methods.

PMID- 15236139
TI  - Intravenous immunoglobulin for severe infections: a survey of Canadian
      specialists.
AB  - PURPOSE: To survey the opinions of Canadian critical care medicine and infectious
      disease specialists about the use of intravenous immunoglobulin (IVIG) for the
      treatment of severe infections. MATERIALS AND METHODS: A scenario-based, cross
      sectional survey of Canadian critical care medicine and infectious disease
      specialists was conducted from March to June 2003. RESULTS: The response rate was
      291/487 (60%). Respondents were primarily medically trained and most (241/291;
      83%) were practicing in large academic referral centers. Physicians reported that
      they would use IVIG in patients with streptococcal toxic shock syndrome (STSS;
      218/288; 76%), streptococcal necrotizing fasciitis without STSS (143/286; 50%),
      staphylococcal toxic shock syndrome (75/288; 26%), streptococcal soft tissue
      infection without NF or STSS (31/286; 11%), and septic shock due to intra
      abdominal focus (9/283; 3%). The majority (> or =67%) of respondents believed
      that it would be ethical to randomize patients to IVIG or placebo in a clinical
      trial in each of the five scenarios. One third (192/286) reported that it would
      not be ethical to randomize patients with STSS. Canadian specialists commonly
      report favoring the use of IVIG to treat STSS and necrotizing fasciitis but less
      commonly endorse this treatment for other infections. CONCLUSION: Specialist's
      beliefs surrounding the efficacy of IVIG would challenge but not preclude the
      conduct of future placebo controlled trials of severe streptococcal infections in
      Canada.

PMID- 15236140
TI  - Clinical practice guideline for the use of noninvasive positive pressure
      ventilation in COPD patients with acute respiratory failure.
AB  - Noninvasive positive pressure ventilation has been demonstrated to be of benefit
      in preventing endotracheal intubation and reducing mortality in specific patients
      in the setting of acute exacerbations of chronic obstructive pulmonary disease.
      The successful application of noninvasive positive pressure ventilation depends
      on a multitude of factors, including patient selection, choice of interface,
      physician experience, and patient-ventilator synchrony. The use of clinical
      practice guidelines has been shown to improve the process and outcomes of care.
      This paper presents a guideline for the use of noninvasive positive pressure
      ventilation in the setting of acute ventilatory failure in patients with acute
      exacerbations of chronic obstructive pulmonary disease.

PMID- 15236141
TI  - Preoperative 24-hour urine amount as an independent predictor of renal outcome in
      poor cardiac function patients after coronary artery bypass grafting.
AB  - PURPOSE: To investigate the incidence and the main pre-operative risk factors for
      the development of acute renal failure (ARF) in triple vessels coronary artery
      bypass grafting (CABG) with special reference to a subset of patients with poor
      cardiac function (ejection fraction <50%). PATIENTS: The study included the
      patients (n = 66) requiring CABG from January 1, 1995 to January 1, 2002 in a
      medical center. RESULTS: A high percentage (84.8%) of patients developed ARF and
      57.6% of patients received hemodialysis (HD). Preoperative variables
      significantly associated with the development of ARF included increased age,
      increased preoperative serum creatinine, decreased preoperative 24-hour urine
      output and accepted emergent CABG. By the logistic multivariate regression model,
      increased age (OR = 1.16), preoperative serum creatinine (OR = 3.58,), decreased
      preoperative 24-hour urine amount (OR = 0.99,) and emergent CABG (OR = 2.01) were
      independently associated with ARF. As for the need for HD, those factors
      including, preoperative serum creatinine (2.11 +/- 1.13 v 3.08 +/- 1.67 mg/dL)
      and preoperative 24-hour urine output (1358.6 +/- 745.9 v 755.2 +/- 572.1 mL/day)
      were significantly associated with requirement of dialysis. Using multivariate
      logistic regression, the significant risk factors independently associated with
      dialysis were preoperative serum creatinine (OR = 1.34) and preoperative 24-hour
      urine output (OR = 0.99). Patients with non- oliguric renal failure had
      significantly greater chance of recovering their renal function after cardiac
      surgery compared to those with oliguria (36.9% v 10.0%, P <.05). CONCLUSION:
      Preoperative 24-hour urine amount and pre-operative serum creatinine can provide
      valuable information for predicting the likelihood of developing acute renal
      failure and requiring dialysis in this subgroup of patients.

PMID- 15236142
TI  - Comparison of nebulized epinephrine and terbutaline in patients with acute severe
      asthma: a controlled trial.
AB  - PURPOSE: To compare the efficacy and tolerability of nebulized adrenaline and
      terbutaline in acute severe asthma. METHODS:  DESIGN: Prospective pilot
      randomized double-blind cross-over trial. SETTING: Emergency department of a
      university hospital. PATIENTS: Thirty-eight patients admitted with severe acute
      asthma. Each patient received adrenaline (3 mg) and terbutaline (5 mg)
      nebulizations over 20 min in randomized order. Additional treatment comprised
      methylprednisolone, intravenous hydration, and oxygen. The efficacy and
      tolerability of the two drugs were evaluated at the end of each nebulization as
      well as potential synergistic effects. RESULTS: Eighteen patients received
      adrenaline first, and 20 received terbutaline first. Peak expiratory flow (PEF)
      improved significantly in both groups after the first nebulization (from 157
      L/min +/- 111 L/min to 199 L/min +/- 134 L/min with adrenaline, P <.01; and from
      142 L/min +/- 65 L/min to 193 L/min +/- 181 L/min with terbutaline, P <.01). Both
      drugs induced a significant decrease in respiratory frequency. The improvement in
      PaO2 was only significant with terbutaline. Respiratory frequency, PEF and PaO2
      were not improved by the second nebulization. No adverse effects were observed.
      CONCLUSIONS: Adrenaline nebulization was as effective and as well tolerated as
      terbutaline in acute severe asthma. No synergistic effect between terbutaline and
      adrenaline was observed.

PMID- 15236143
TI  - Iced versus room temperature injectate for assessment of cardiac output,
      intrathoracic blood volume, and extravascular lung water by single transpulmonary
      thermodilution.
AB  - PURPOSE: To assess the accuracy of iced versus room (RT) temperature single
      transpulmonary thermodilution (STPD) measurements for cardiac output, intra
      thoracic blood, volume and extravascular lung water. MATERIALS AND METHODS: We
      studied 15 critically ill patients in a surgical intensive care unit with
      sepsis/septic shock (n = 8), pancreatitis (n = 2), acute liver failure (n = 2),
      orthotopic liver transplantation (n = 2) and lung resection (n = 1). All patients
      were sedated and mechanically ventilated. A 4-French femoral arterial catheter
      was inserted into each patient and connected to the pulse contour computer system
      (PiCCO). The pulse contour computer was then consecutively calibrated by
      triplicate STPD with 20 mL of RT and iced saline solution. The measurements with
      RT injectate were performed with a special in-line sensor adapted for measurement
      with RT injectate. All measurements were completed in less than 10 min. RESULTS:
      A total of 144 measurements were carried out. Linear regression analysis revealed
      good correlation between the two methods [r = 0.95; r = 0.91 and r = 0.97 for
      iced v RT cardiac index (CI), intrathoracic blood volume index (ITBVI) and
      extravascular lung water index (ELWI) respectively]. The bias +/- 2 * standard
      deviation of difference was -0.2 +/- 0.7 L/min/m2 for CIIT v CIRT; -4,9 +/- 194
      mL/m2 for ITBVIIT v ITBVIRT and -0.535 +/- 1,5 mL/kg for ELWIIT v ELWIRT. CIRT
      and ELWIRT were measured slightly higher compared to IT injectate (P <.05).
      CONCLUSIONS: CI, ITBVI, and ELWI assessed by STPD with RT injectate are well
      correlated with measurements by iced injectates. According to our results room
      temperature injectates can be used in critically ill patients for assessment of
      CI, ITBVI and ELWI, which is more convenient for both the patients and medical
      staff and is also less expensive.

PMID- 15236144
TI  - A content analysis of forms, guidelines, and other materials documenting end-of
      life care in intensive care units.
AB  - OBJECTIVE: The purpose of this study was to determine the extent to which data
      entry forms, guidelines, and other materials used for documentation in intensive
      care units (ICUs) attend to 6 key end-of-life care (EOLC) domains: 1) patient and
      family-centered decision making, 2) communication, 3) continuity of care, 4)
      emotional and practical support, 5) symptom management and comfort care, and 6)
      spiritual support. A second purpose was to determine how these materials might be
      modified to include more EOLC content and used to trigger clinical behaviors that
      might improve the quality of EOLC. PARTICIPANTS: Fifteen adult ICUs-8 medical, 2
      surgical, and 4 mixed ICUs from the United States, and 1 mixed ICU in Canada, all
      affiliated with the Critical Care End-of-Life Peer Workgroup METHODS: Physician
      nurse teams in each ICU received detailed checklists to facilitate and
      standardize collection of requested documentation materials. Content analysis was
      performed on the collected documents, aimed at characterizing the types of
      materials in use and the extent to which EOLC content was incorporated.
      MEASUREMENTS AND MAIN RESULTS: The domain of symptom management and comfort care
      was integrated most consistently on forms and other materials across the 15 ICUs,
      particularly pain assessment and management. The 5 other EOLC domains of patient
      and family centered decision-making, communication, emotional and practical
      support, continuity of care, and spiritual support were not well-represented on
      documentation. None of the 15 ICUs supplied a comprehensive EOLC policy or EOLC
      critical pathway that outlined an overall, interdisciplinary, sequenced approach
      for the care of dying patients and their families. Nursing materials included
      more cues for attending to EOLC domains and were more consistently preprinted and
      computerized than materials used by physicians. Computerized forms concerning
      EOLC were uncommon. Across the 15 ICUs, there were opportunities to make EOLC-
      related materials more capable of triggering and documenting specific EOLC
      clinical behaviors. CONCLUSIONS: Inclusion of EOLC items on ICU formatted data
      entry forms and other materials capable of triggering and documenting clinician
      behaviors is limited, particularly for physicians. Standardized scales,
      protocols, and guidelines exist for many of the EOLC domains and should be
      evaluated for possible use in ICUs. Whether such materials can improve EOLC has
      yet to be determined.

PMID- 15236145
TI  - Distress of clinicians with decisions to withhold or withdraw life-support
      measures.

PMID- 15236160
TI  - Study may improve survival of transplanted livers.

PMID- 15236161
TI  - Howard Hughes Medical Institute seeks 50 new research fellows.

PMID- 15236162
TI  - CME series focuses on Patient-Centered GI Practice.

PMID- 15236163
TI  - NIH opens training grants to foreign students.

PMID- 15236164
TI  - An argument for identifying highly cited papers on biographical sketches.

PMID- 15236165
TI  - Ileocecal Burkitt's lymphoma.

PMID- 15236166
TI  - MYH mutations in patients with attenuated and classic polyposis and with young
      onset colorectal cancer without polyps.
AB  - BACKGROUND & AIMS: MYH-associated polyposis is a recently described disease that
      is characterized by multiple colorectal adenomas and a recessive pattern of
      inheritance. Individuals with MYH-associated polyposis have biallelic mutations
      in MYH, a base excision repair gene, and are negative for germline mutations in
      the APC gene. In this study, the 2 most prevalent MYH mutations in white persons,
      Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3
      groups: 400 undergoing screening colonoscopy and found to have 0-3 polyps, 444
      with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which
      a germline mutation was not identified. METHODS: Genotyping for Y165C and G382D
      was performed by Pyrosequencing. RESULTS: Biallelic mutations for Y165C and/or
      G382D were not found in any of those undergoing screening colonoscopy with 0-3
      polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n =
      26), or in those with CRC who were older than 50 years (n = 328). Furthermore,
      these 2 MYH mutations were not found among patients whose tumors showed the
      presence of defective DNA mismatch repair (n = 62). However, the presence of
      biallelic germline MYH mutations correlated with the presence of >or=20
      adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at
      50 years of age or younger also presented with biallelic germline mutations in
      MYH. CONCLUSIONS: These data suggest that screening of MYH should be considered
      not only in patients with multiple polyps but also in patients with early-onset
      CRC.

PMID- 15236167
TI  - Kupffer of Kupffer cells.

PMID- 15236168
TI  - Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations:
      impact on counseling and surveillance.
AB  - BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused
      by a mutated mismatch repair (MMR) gene. The aim of our study was to determine
      the cumulative risk of developing cancer in a large series of MSH6 mutation
      carriers. METHODS: Mutation analysis was performed in 20 families with a germline
      mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2
      mutation carriers. Microsatellite instability (MSI) analysis and
      immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A
      total of 146 MSH6 mutation carriers were identified. In these carriers, the
      cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71%
      for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related
      tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P
      = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was
      significantly lower (P = 0.0049) and the risk for endometrial cancer
      significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male
      carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but
      the difference was not significant (P = 0.0854). MSI analysis in colorectal
      tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had
      a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend
      starting colonoscopic surveillance in female MSH6 mutation carriers from age 30
      years. Prophylactic hysterectomy might be considered in carriers older than 50
      years. MSI and IHC analysis are sensitive tools to identify families eligible for
      MSH6 mutation analysis.

PMID- 15236169
TI  - Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X
      receptor target genes.
AB  - BACKGROUND & AIMS: Phase 1, phase 2, and cellular efflux transporters are
      critical components in intestinal barrier function against xenobiotics and
      bacteria. We therefore performed global gene expression profiling in patients
      with ulcerative colitis (UC) and Crohn's disease as well as control specimens,
      with a special emphasis on genes involved in detoxification and epithelial
      membrane integrity. METHODS: Mucosal biopsy specimens from nonaffected regions of
      the colon and the terminal ileum were subjected to DNA microarray analysis and
      pathway-related data mining. Real-time reverse-transcription polymerase chain
      reaction was used for verification of selected regulated candidate genes in
      larger inflammatory bowel disease sample numbers and intestinal cell lines.
      RESULTS: Several dysregulated genes were identified in both disease groups and
      tissues. A set of genes coordinately down-regulated in the colon of patients with
      UC was composed of cellular detoxification and defense genes, which are target
      genes for the transcription factor pregnane X receptor (PXR). Messenger RNA
      expression of ABCB1 (MDR1) and PXR was significantly reduced in the colon of
      patients with UC but was unaffected in patients with Crohn's disease. In contrast
      to some of its target genes, the expression of PXR was not sensitive to tumor
      necrosis factor alpha stimulation of intestinal cell lines. CONCLUSIONS: A
      disease- and tissue-specific decrease in the expression of detoxification enzymes
      and ABC transporters was observed, which may be explained by a loss of PXR
      expression. Thus, dysregulation of xenobiotic metabolism and PXR activity in the
      gut is likely to contribute to the pathophysiology of UC.

PMID- 15236170
TI  - Computed tomographic colonography compared with colonoscopy in patients at
      increased risk for colorectal cancer.
AB  - BACKGROUND & AIMS: To date, computed tomographic (CT) colonography has been
      compared with an imperfect test, colonoscopy, and has been mainly assessed in
      patients with positive screening test results or symptoms. Therefore, the
      available data may not apply to screening of patients with a personal or family
      history of colorectal polyps or cancer (increased risk). We prospectively
      investigated the ability of CT colonography to identify individuals with large
      (>or=10 mm) colorectal polyps in consecutive patients at increased risk for
      colorectal cancer. METHODS: A total of 249 consecutive patients at increased risk
      for colorectal cancer underwent CT colonography before colonoscopy. Two reviewers
      interpreted CT colonography examinations independently. Sensitivity, specificity,
      and predictive values were determined after meticulous matching of CT
      colonography with colonoscopy. Unexplained large false-positive findings were
      verified with a second-look colonoscopy. RESULTS: In total, 31 patients (12%) had
      48 large polyps at colonoscopy. This included 8 patients with 8 large polyps that
      were overlooked initially and detected at the second-look colonoscopy. In 6 of 8
      patients, the missed polyp was the only large lesion. With CT colonography, 84%
      of patients (26/31) with large polyp(s) were identified, paired for a specificity
      of 92% (200-201/218). Positive and negative predictive values were 59%-60% (26/43
      44) and 98% (200-201/205-206), respectively. CT colonography detected 75%-77% (36
      37/48) of large polyps, with 9 of the missed lesions being flat. CONCLUSIONS: CT
      colonography and colonoscopy have a similar ability to identify individuals with
      large polyps in patients at increased risk for colorectal cancer. The large
      proportion of missed flat lesions warrants further study.

PMID- 15236171
TI  - Abnormal predefecatory colonic motor patterns define constipation in obstructed
      defecation.
AB  - BACKGROUND & AIMS: The pathophysiology of constipation in the syndrome of
      obstructed defecation is unknown. Using 24-hour pancolonic manometric recordings
      of the unprepared colon to record basal pressures and spontaneous defecation
      episodes, we tested the hypothesis that the frequency, timing, or spatial
      distribution of propagating colonic pressure waves is abnormal in patients with
      obstructed defecation. METHODS: In 11 patients with obstructed defecation and 16
      healthy controls, pressures were recorded using a nasocolonic catheter that was
      positioned such that 16 recording sites spanned the unprepared colon at 7.5-cm
      intervals. RESULTS: The overall frequency of propagating sequences (PS) in the
      colon did not differ between patients and controls. When compared with controls,
      patients had a significant increase in the frequency of retrograde and antegrade
      PS (P < 0.05) in the left colon and a significant reduction in the amplitude of
      propagating pressure waves throughout the entire colon (P < 0.03). Defecation
      occurred in 6 of 11 patients and 9 of 16 controls. In the 15 minutes before
      defecation, controls showed a highly significant increase in frequency (P =
      0.001) and amplitude (P = 0.01) of PS. In contrast, patients did not demonstrate
      this or the typical spatiotemporal organization of PS normally observed before
      expulsion of stool. CONCLUSIONS: Patients with obstructed defecation lack the
      normal predefecatory augmentation in frequency and amplitude of propagating
      pressure waves and lack the normal stereotypic spatiotemporal patterning of
      colonic pressure waves that would normally culminate in effective expulsion of
      stool.

PMID- 15236172
TI  - Laryngo-upper esophageal sphincter contractile reflex in humans deteriorates with
      age.
AB  - BACKGROUND & AIMS: Recent studies have shown the existence of several reflex
      connections between the aerodigestive and upper gastrointestinal tracts. Our aim
      was to study the effect of laryngeal stimulation on upper esophageal sphincter
      (UES) pressure and to determine the reproducibility of this effect. METHODS: We
      studied 14 young and 10 elderly healthy nonsmoker volunteers and 7 patients with
      UES dysphagia using a concurrent manometric and video endoscopic technique. Three
      levels of laryngeal air stimulation were studied: 6 mm Hg/50 ms, 10 mm Hg/50 ms,
      and 6 mm Hg/2 s. Ten young subjects were studied twice. RESULTS: For 6-mm Hg/2-s
      and 6-mm Hg/50-ms duration stimuli, the frequency of UES response to air
      stimulation as evidenced by mucosal deflection (response/deflection ratio) in the
      elderly volunteers was significantly lower compared with that of young subjects
      (P < 0.05). The response/deflection ratio of the 6-mm Hg/2-s stimulus was
      significantly higher than those induced by stimuli of shorter duration (P <
      0.01). Poststimulation UES pressure was significantly higher than prestimulation
      pressure (P < 0.05) in both groups. The magnitude of the increase in
      poststimulation UES pressure in the elderly volunteers was similar to that of the
      young subjects. Findings were similar in repeated studies. Four of 7 dysphagic
      patients exhibited an abnormal response. CONCLUSIONS: Afferent signals
      originating from the larynx reproducibly induce contraction of the UES: the
      laryngo-UES contractile reflex. This reflex is elicited most reliably by 6-mm
      Hg/2-s air stimulation. Frequency elicitation of this reflex decreases
      significantly with age while the magnitude of change in UES pressure remains
      unchanged, indicating a deleterious effect of aging on the afferent arm of this
      reflex. This reflex is altered in some dysphagic patients.

PMID- 15236173
TI  - Inhibition of neutral sodium absorption by a prostaglandin analogue in patients
      with cystic fibrosis.
AB  - BACKGROUND & AIMS: In normal intestine, cyclic nucleotides (adenosine 3',5'
      cyclic monophosphate [cAMP], guanosine 3',5'-cyclic monophosphate) and Ca(2+)
      inhibit neutral sodium absorption. In contrast, in the jejunum of a knockout
      mouse model of cystic fibrosis (CF), agents that elevate intracellular cAMP
      levels did not inhibit neutral sodium absorption, suggesting that the
      antiabsorptive effect of cAMP is dependent on the cystic fibrosis transmembrane
      conductance regulator (CFTR). The aim of the present study was to determine if a
      prostaglandin E(1) analogue, which causes elevation of intracellular cAMP and
      Ca(2+) levels, inhibits neutral sodium absorption in patients with CF in vivo.
      METHODS: Electrolyte and water absorption/secretion was measured during steady
      state perfusion of the jejunum with a balanced electrolyte solution. Patients
      with CF and healthy subjects were studied under basal conditions and during
      intraluminal infusion of a prostaglandin E(1) analogue (misoprostol). RESULTS:
      The rate of neutral sodium absorption in the basal state was similar in healthy
      subjects and patients with CF. Prostaglandin infusion markedly reduced neutral
      sodium absorption in both healthy subjects and patients with CF. Prostaglandin
      caused high rates of electrolyte and water secretion in healthy subjects but only
      trivial rates of secretion in patients with CF. CONCLUSIONS: CFTR mutations
      causing CF in humans do not prevent prostaglandin E(1) inhibition of neutral
      sodium absorption, even though these mutations produce a severe defect in
      prostaglandin-stimulated electrolyte secretion. These findings suggest that an
      intact antiabsorptive response to either cAMP or Ca(2+) may contribute to the
      relatively low level of intestinal disease in patients with CF.

PMID- 15236174
TI  - IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease
      the risk of reflux esophagitis.
AB  - BACKGROUND & AIMS: Proinflammatory interleukin (IL)-1 gene polymorphisms
      associated with high levels of IL-1beta activity increase the risk for
      hypochlorhydria and distal gastric carcinoma. The aim of this study was to
      evaluate whether carriers of these polymorphic genes are protected against
      gastroesophageal reflux disease (GERD). TNFA-308 polymorphisms were also studied.
      METHODS: We prospectively evaluated 385 patients without gastric cancer and
      peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were
      successfully genotyped for all cytokines studied. The cagA status of Helicobacter
      pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31,
      IL1RN, and TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment
      length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was
      assessed according to the updated Sydney system. The role of the proinflammatory
      cytokine genotypes in the genesis of GERD was evaluated before and after
      stratification by H. pylori status in logistic regression models controlling for
      confounding factors. RESULTS: IL1B-31 (a near-complete linkage disequilibrium
      between polymorphism at -31 and -511 was found) and IL1RN*2 allele polymorphisms
      were associated with GERD. After stratification, in the group of H. pylori
      positive patients, cagA-positive status, IL1B-31 polymorphic alleles, IL1RN*2
      alleles, and the degree of corpus gastritis were negatively associated with GERD.
      In the H. pylori-negative group, IL1B-31C/C genotype was inversely associated
      with GERD even after adjustment for age and sex. CONCLUSIONS: This study provides
      evidence supporting the independent protective role of cagA-positive H. pylori
      status and IL1B and ILRN allele polymorphisms against GERD.

PMID- 15236175
TI  - Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon
      cancer.
AB  - BACKGROUND & AIMS: Altered mucosal glycosylation in inflammatory bowel disease
      and colon cancer could affect mucosal bacterial adherence. This study aimed to
      quantify and characterize mucosa-associated and intramucosal bacteria,
      particularly Escherichia coli, in these conditions. METHODS: Mucosa-associated
      bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples
      obtained at colonoscopy (Crohn's disease, n = 14 patients; ulcerative colitis, n
      = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n =
      21). Intramucosal bacteria were grown after gentamicin treatment followed by
      hypotonic lysis. RESULTS: Mucosa-associated and intramucosal bacteria were
      cultured more commonly in Crohn's disease (79%, P = 0.03; and 71%, P < 0.01,
      respectively), but not ulcerative colitis (38% and 48%), than in noninflamed
      controls (42% and 29%) and were commonly cultured from colon cancers (71% and
      57%). Mucosa-associated E. coli, which accounted for 53% of isolates, were more
      common in Crohn's disease (6/14; 43%) than in noninflamed controls (4/24, 17%),
      as also were intramucosal E. coli: Crohn's disease, 29%; controls, 9%. E. coli
      expressed hemagglutinins in 39% of Crohn's cases and 38% of cancers but only 4%
      of controls, and this correlated (P = 0.01) with adherence to the I407 and HT29
      cell lines. Invasion was cell-line dependent. E. coli, including nonadherent
      isolates, induced interleukin-8 release from the cell lines. E. coli adhesins
      showed no blood group specificity, excepting 1 cancer isolate (HM44) with
      specificity for the Thomsen-Friedenreich antigen, but they could be blocked by
      soluble plantain fiber. CONCLUSIONS: These studies support a central role for
      mucosally adherent bacteria in the pathogenesis of Crohn's disease and colon
      cancer. Soluble plant fibers that inhibit their adherence have therapeutic
      potential.

PMID- 15236176
TI  - The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and
      prostaglandin metabolism in cyclooxygenase knockout mice.
AB  - BACKGROUND & AIMS: Insight into the role of the different cyclooxygenase isoforms
      in prostaglandin biosynthesis, surface hydrophobicity, and gastric mucosal
      barrier integrity can be gained by comparing the effects of luminal damaging
      agents in wild-type and cyclooxygenase knockout mice. METHODS: Fasted wild-type,
      cyclooxygenase-1, and cyclooxygenase-2 knockout mice were intragastrically
      administered saline, 0.6N HCl, or aspirin (aspirin 20 mmol/L) in combination with
      0.6N HCl and killed 1 hour later, at which time the gastric lesion score was
      assessed and biopsy samples were taken for surface, biochemical, and
      morphological analyses. RESULTS: The gastric mucosa of cyclooxygenase-1 knockout
      mice was more severely injured by both HCl alone and aspirin/HCl than that of
      wild-type and cyclooxygenase-2 knockout mice. HCl alone and aspirin/HCl also
      induced a more profound decrease in surface hydrophobicity in cyclooxygenase-1
      knockout mice than in wild-type mice, whereas this surface property was
      unaffected in cyclooxygenase-2 knockout mice. The gastric injury induced by
      aspirin/HCl in cyclooxygenase-1 knockout mice could be prevented if the animals
      were treated with phosphatidylcholine-associated aspirin. Aspirin/HCl, in
      comparison to saline or HCl alone, induced a 4-6-fold increase in gastric mucosal
      prostaglandin E(2) concentration in the cyclooxygenase-1 knockout mice, whereas
      it decreased prostaglandin E(2) levels in wild-type and cyclooxygenase-2 knockout
      mice. This paradoxical aspirin-induced increase in gastric prostaglandin E(2) in
      cyclooxygenase-1 knockout mice seemed to correspond to an increase in
      cyclooxygenase-2 messenger RNA and protein expression. The gastric lesion score
      seemed to be significantly associated with alterations in surface hydrophobicity
      but not with mucosal prostaglandin E(2) concentration. CONCLUSIONS: Our evidence
      on cyclooxygenase knockout mice suggests that aspirin predominantly causes
      gastric injury by a non-prostaglandin mechanism, perhaps by attenuating surface
      hydrophobicity, a possibility supported by the low gastric toxicity of
      phosphatidylcholine/aspirin. However, prostaglandins generated by cyclooxygenase
      1 may play an important permissive role in maintaining gastric mucosal barrier
      integrity. Aspirin seems to paradoxically increase the gastric mucosal
      prostaglandin E(2) concentration in cyclooxygenase-1 knockout mice, possibly by
      the induction of cyclooxygenase-2.

PMID- 15236177
TI  - T helper-2 immunity regulates bronchial hyperresponsiveness in eosinophil
      associated gastrointestinal disease in mice.
AB  - BACKGROUND & AIMS: Eosinophil-associated gastrointestinal diseases are frequently
      associated with extraintestinal features, including bronchopulmonary
      manifestations. The factors predisposing to bronchial hyperresponsiveness in
      eosinophil-associated gastrointestinal diseases are unknown. To elucidate the
      mechanistic link between eosinophil-associated gastrointestinal diseases and
      bronchial hyperresponsiveness, we used murine models of eosinophil-associated
      gastrointestinal diseases and eotaxin-1/transgene-induced eosinophil-associated
      gastrointestinal diseases. METHODS: Mice were sensitized and orally challenged
      with ovalbumin-coated encapsulated particles to induce eosinophil-associated
      gastrointestinal disease, and bronchial responsiveness was examined. Furthermore,
      transgenic mice expressing eotaxin in the intestine (with the rat fatty acid
      binding promoter) were used to specifically elucidate the contribution of this
      chemokine in eosinophil-associated gastrointestinal disease-associated bronchial
      hyperresponsiveness. RESULTS: The induction of allergen-induced eosinophil
      associated gastrointestinal disease was directly correlated with the development
      of bronchial hyperresponsiveness. The development of bronchial
      hyperresponsiveness in mice with allergen-induced eosinophil-associated
      gastrointestinal disease was dependent on eotaxin expression in the
      gastrointestinal tract. Expression of eotaxin in the gastrointestinal tract of
      transgenic mice was sufficient to promote bronchial hyperresponsiveness.
      Bronchial hyperresponsiveness was shown to be directly linked to the aberrant
      CD4(+) T helper 2 lymphocyte production of interleukin-13. It is interesting to
      note that transgenic expression of eotaxin was linked with enhanced T helper 2
      lymphocyte/cytokine synthesis (interleukin-4, -5, and -13) and the production of
      mucosal immunoglobulin G1 in the gastrointestinal lumen. We also showed that
      eotaxin treatment of CD4(+) T cells enhanced interleukin-13 production in vitro.
      CONCLUSIONS: These studies suggest that increased expression of eotaxin in the
      gastrointestinal compartment can lead to increased CD4(+) T cell-derived T helper
      2 lymphocyte-cytokine production that drives aberrant immunophysiological
      responses in distant noninflamed mucosal tissue (the lung). These results provide
      a possible explanation for the altered lung function seen in some patients with
      inflammatory gastrointestinal disorders.

PMID- 15236178
TI  - A novel triterpenoid induces transforming growth factor beta production by
      intraepithelial lymphocytes to prevent ileitis.
AB  - BACKGROUND & AIMS: The loss of homeostasis is a hallmark of inflammatory bowel
      disease. Oral infection of susceptible mice with Toxoplasma gondii results in an
      acute lethal ileitis characterized by increased interferon gamma, tumor necrosis
      factor alpha, and inducible nitric oxide synthase; homeostasis results from
      transforming growth factor beta production by intraepithelial lymphocytes. The
      synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid
      (CDDO) is a potent anti-inflammatory molecule previously shown in vitro to
      suppress the de novo synthesis of inducible nitric oxide synthase and to induce
      the transcription and activation of genes from the transforming growth factor
      beta signaling pathway. METHODS: We evaluated the immune response in the small
      intestine and by intraepithelial lymphocytes after a single intraperitoneal dose
      of CDDO at the time of T. gondii oral infection. We abrogated the homeostatic
      effects of CDDO by blocking transforming growth factor beta in vivo. RESULTS:
      CDDO acid prevented ileitis development through the global down-regulation of
      inflammatory cytokines and chemokines. Total transforming growth factor beta(1)
      production by the intraepithelial lymphocytes increased, as did Smad2 expression.
      Blocking transforming growth factor beta reversed CDDO-induced protection and
      prevented the up-regulation of Smad2 in the small intestine. CONCLUSIONS: CDDO
      acid is a novel anti-inflammatory molecule capable of preventing ileitis by
      activating the transforming growth factor beta signaling pathway in a pathogen
      driven ileitis model. This could represent a new treatment of inflammatory bowel
      disease.

PMID- 15236179
TI  - Evidence for the role of angiotensin II biosynthesis in the rat internal anal
      sphincter tone.
AB  - BACKGROUND & AIMS: The internal anal sphincter tone is important for anorectal
      continence. This study examined the role of angiotensin II as a neurohumoral
      signal for the myogenic tone in the internal anal sphincter. METHODS: We
      determined the effect of angiotensin I, II, III, and IV and angiotensin-(1-7) on
      the basal tone of the rat internal anal sphincter smooth muscle before and after
      selective receptor antagonists and biosynthesis inhibitors. Selective
      pharmacological tools used were losartan (for the AT(1) receptor), PD123,319 (for
      AT(2)), A-779 [for angiotensin-(1-7)], captopril (for angiotensin-converting
      enzyme), and amastatin (for aminopeptidases A and N). Angiotensins were measured
      by using high-performance liquid chromatography/UV. Western blot studies were
      used to determine AT(1) and AT(2) receptors, ACE, and aminopeptidases A and N.
      RESULTS: Angiotensin I, II, and III produced concentration-dependent contraction
      in the internal anal sphincter mediated by AT(1) receptors. However, in the
      higher concentrations (from 100 nM to 10 microM), angiotensin II showed an
      inhibitory effect via AT(2) receptors. Captopril (1 microM) inhibited the
      biosynthesis of angiotensin II in the internal anal sphincter, antagonized the
      contractile effects of angiotensin I, and, importantly, caused a decrease in the
      basal tone. Amastatin inhibited the effects of angiotensin II while augmenting
      those of angiotensin III. In contrast, angiotensin-(1-7) and angiotensin IV had
      only minor effects in the internal anal sphincter. Angiotensin I, II, and III;
      angiotensin-converting enzyme; aminopeptidase A and aminopeptidase n; at(1); and
      at(2) receptors were shown to be present in the internal anal sphincter.
      CONCLUSIONS: Locally produced angiotensin II may partially regulate basal tone in
      the internal anal sphincter.

PMID- 15236180
TI  - A novel, noninvasive method for the measurement of intestinal fat absorption.
AB  - BACKGROUND & AIMS: The goal of the study was to facilitate fat balance
      measurements with an appropriate intestinal marker for the transit of dietary fat
      and thereby eliminate the need for complete diet and fecal collections. METHODS:
      Dietary fat containing 5% sucrose polybehenate was fed in a semisynthetic diet to
      rats and mice. Fat absorption was calculated from the ratios of behenic acid to
      other fatty acids in diet and feces as analyzed by gas chromatography of fatty
      acid methyl esters. The method was validated by measuring absorption of well
      absorbed (safflower oil) and poorly absorbed (olestra; calcium soaps) dietary
      fats. The animals were fed meals containing test fats for 2 or 3 days, and fecal
      samples were collected. Fecal samples of approximately 10 mg (single fecal pellet
      from mice) were assayed. RESULTS: The method yielded values that were consistent
      with complete absorption of safflower oil and the nonabsorbability of olestra and
      calcium soaps. The results were reproducible and consistent among individual
      fecal aliquots. The method was compared with traditional fat-balance methods in
      animals fed both high- and low-fat diets. CONCLUSIONS: Sucrose polybehenate is an
      appropriate marker that allows the rapid measurement of fat absorption by
      analyzing aliquots of <1% of total feces. The method is noninvasive, does not
      require isotope analyses, and can be carried out as part of an animal's normal
      feeding regimen. The method may be a facile technique to assess fat absorption
      measurements in humans.

PMID- 15236181
TI  - Gastric parietal cell acid secretion in mice can be regulated independently of
      H/K ATPase endocytosis.
AB  - BACKGROUND & AIMS: Gastric parietal cells secrete acid into the lumen of the
      stomach. They express a proton pump, the gastric H(+)/K(+) ATPase, the activity
      of which is tightly regulated. The H(+)/K(+) ATPase traffics between an
      intracytoplasmic compartment (tubulovesicles) in quiescent parietal cells and the
      apical plasma membrane in activated cells. These trafficking events are
      considered to contribute to the control of acid secretion by modulating access to
      apical K(+) and Cl(-) conductances that are required for transmembrane H(+) ion
      transport by the H(+)/K(+) ATPase. Here, we have determined whether the control
      of acid secretion in vivo requires membrane trafficking of the H(+)/K(+) ATPase.
      METHODS: We developed mice that only express an H(+)/K(+) ATPase beta subunit in
      which a putative tyrosine-based endocytosis motif in the cytoplasmic tail is
      mutated. Location of the H(+)/K(+) ATPase and parietal cell ultrastructure and
      gastric acid secretion were then examined. RESULTS: Parietal cells of these mice
      lacked a tubulovesicular compartment, and the H(+)/K(+) ATPase was resident
      exclusively on the apical plasma membrane. Despite the inability of the H(+)/K(+)
      ATPase to be endocytosed, the gastric acid secretory response to histamine or an
      antagonist was very similar to that of wild-type mice, indicating that control of
      H(+)/K(+) ATPase activity can occur independently of intracellular trafficking.
      CONCLUSIONS: We were able to dissociate the regulation of H(+)/K(+) ATPase
      activity from intracellular trafficking of the protein. Thus, it is likely that
      direct regulation of apical K(+) and Cl(-) conductances are sufficient to control
      gastric acid secretion.

PMID- 15236182
TI  - Mouse mast cell protease-1 is required for the enteropathy induced by
      gastrointestinal helminth infection in the mouse.
AB  - BACKGROUND & AIMS: The relationship between intestinal pathology and immune
      expulsion of gastrointestinal nematodes remains controversial. Immune expulsion
      of gastrointestinal helminth parasites is usually associated with Th2 responses,
      but the effector mechanisms directly responsible for parasite loss have not been
      elucidated. Mast cell hyperplasia is a hallmark of infection with
      gastrointestinal nematodes, in particular Trichinella spiralis. Although the
      precise mechanism by which mast cells induce expulsion of these parasites has not
      been elucidated, it has been proposed that mast cell mediators, including
      cytokines and granule chymases, act to create an environment inhospitable to the
      parasite, part of this being the induction of intestinal inflammation. Therefore,
      the aims of this study were to dissect the role of mast cells and mast cell
      proteases in the induction of parasite-induced enteropathy. METHODS: Mast cell
      deficient W/Wv and mouse mast cell protease-1 (mMCP-1)-deficient mice were
      infected with T. spiralis, and parasite expulsion, enteropathy, and Th2 responses
      were determined. RESULTS: Expulsion of the parasite was delayed in both strains
      of mice compared with wild-type controls; additionally, in both cases, the
      enteropathy was significantly ameliorated. Although Th2 responses were
      significantly reduced in mast cell-deficient W/Wv mice, those from mMCP-1
      deficient mice were similar to wild-type mice. Additionally, levels of TNF-alpha
      and nitric oxide were significantly reduced in both W/Wv and mMCP-1 deficient
      mice. CONCLUSIONS: These results imply that mast cells may contribute to the
      induction of protective Th2 responses and, importantly, that the intestinal
      inflammation associated with gastrointestinal helminths is partly mediated by
      mMCP-1.

PMID- 15236183
TI  - Splanchnic and pelvic mechanosensory afferents signal different qualities of
      colonic stimuli in mice.
AB  - BACKGROUND & AIMS: Mechanosensory information from the colon is conducted via
      lumbar splanchnic nerves (LSN) and sacral pelvic nerves (PN) to the spinal cord.
      The precise nature of mechanosensory information encoded by each pathway has
      remained elusive. Here, we characterize and directly compare the properties of
      mechanosensitive primary afferents from these 2 pathways. METHODS: Using a novel
      in vitro mouse colon preparation, mechanosensitive primary afferents were
      recorded from the LSN and PN and distinguished based on their response to
      receptive field stimulation with 3 distinct mechanical stimuli: probing (70 mg-4
      g), circular stretch (1-5 g), and mucosal stroking (10-1000 mg). RESULTS: Five
      different classes of afferent were recorded from the LSN and PN. Three of these
      classes of afferent (serosal, muscular, and mucosal) were conserved between both
      pathways; however, their respective proportions, receptive field distributions,
      and response properties differed greatly. In general, these 3 classes of afferent
      recorded from the PN responded to lower stimulation intensities, displayed
      greater response magnitudes, and adapted less completely to mechanical
      stimulation compared with their LSN counterparts. In addition, the LSN and PN
      each contain a specialized class of afferent (mesenteric and muscular/mucosal),
      which is unique to their respective pathway. CONCLUSIONS: The splanchnic and
      pelvic pathways contain distinct populations of mechanosensitive afferents. These
      afferents are capable of detecting an array of mechanical stimuli and are
      individually tuned to detect the type, magnitude, and duration of the stimulus.
      This knowledge contributes to our understanding of the role that these 2 pathways
      play in conveying mechanical information from the colon.

PMID- 15236184
TI  - Visceral hyperalgesia and intestinal dysmotility in a mouse model of
      postinfective gut dysfunction.
AB  - BACKGROUND & AIMS: We established the concept that transient enteric infection
      may lead to persistent gut dysfunction, evident in vitro, in nematode-infected
      mice. The present study determined whether gut dysfunction in this model involves
      motor and sensory changes reminiscent of changes found in patients with
      postinfective irritable bowel syndrome (PI-IBS) and investigated underlying
      mechanisms. METHODS: Mice infected up to 70 days previously with Trichinella
      spiralis (Tsp) underwent videofluoroscopy with image analysis to assess upper
      gastrointestinal motility. Pseudoaffective responses to colorectal distention
      (CRD) were assessed using a barostat and validated by single fiber recordings
      from spinal nerves during CRD. Tissues were examined at different time points for
      histology, immunohistochemistry, and cytokine analysis. Some mice received
      dexamethasone intraperitoneally on days 23-25 PI or Tsp antigen orally on days
      29, 43, and 57 PI. RESULTS: From day 28 PI, no discernible inflammation was
      present in the gut. Frequency and propagation velocity of intestinal contractions
      decreased, and retroperistalsis increased at days 28 to 42 PI. CRD induced an
      allodynic and hyperalgesic response in PI mice, which was accompanied by
      increased single unit discharge. Gavage of Tsp antigen induced T-cell responses
      and sustained gut dysfunction for 70 days PI. Administration of dexamethasone
      postinfection normalized dysmotility and visceral hyperalgesia. CONCLUSIONS: Long
      lasting gut dysmotility and hyperalgesia develop in mice after transient
      intestinal inflammation. These changes are maintained by luminal exposure to
      antigen and reversed by corticosteroid treatment. The findings prompt
      consideration of this as a model of PI-IBS.

PMID- 15236185
TI  - Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a
      human enterochromaffin cell model.
AB  - BACKGROUND & AIMS: The aim was to determine whether adenosine receptors modulate
      cAMP, intracellular free calcium ([Ca(2+)](i)), and 5-hydroxytryptamine (5-HT)
      release in human carcinoid BON cells. METHODS: Adenosine receptor (R) mRNA,
      proteins, and function were identified by Western blots, immunofluorescent
      labeling, Fluo-4/AM [Ca(2+)](i) imaging, and pharmacologic/physiologic
      techniques. RESULTS: A1, A2, and A3Rs were present in BON cells and carcinoid
      tumors. Baseline 5-HT levels increased with adenosine deaminase, activation of
      A2Rs, and inhibition of A3Rs, whereas A3R activation decreased 5-HT. A2R
      antagonists or blockade of adenosine reuptake that elevates extracellular
      adenosine reduced mechanically evoked 5-HT release. In single BON cells, touch
      elevated [Ca(2+)](i) responses were augmented by adenosine deaminase, A1, and A3R
      antagonists. CONCLUSIONS: Tonic or mechanically evoked release of endogenous
      adenosine is a critical determinant of differential activation of adenosine
      receptors and may have important implications for gut mechanosensory reflexes.

PMID- 15236186
TI  - Age and diet act through distinct isoforms of the class II transactivator gene in
      mouse intestinal epithelium.
AB  - BACKGROUND & AIMS: Normal weaning induces class II major histocompatibility
      complex (Ia) and invariant chain (Ii) expression in the mouse intestinal
      epithelium. Because the class II transactivator protein (CIITA) induces Ia and Ii
      in most cell types, we hypothesized that diet-induced expression of these genes
      was through CIITA. METHODS: Mouse litters were split and weaned onto an elemental
      diet or a normal (complex) chow diet. On days 24, 31, and 45, epithelial cells
      were isolated from small intestine with EDTA, and the RNA was extracted from both
      wild-type and interferon (IFN)-gamma receptor knockout mice. Messenger RNA (mRNA)
      was measured by Northern blotting, RNase protection assay, and real-time
      polymerase chain reaction and Ia localized by immunohistochemistry. RESULTS: By
      day 31, CIITA mRNA was induced in the intestinal epithelium of normally weaned
      wild-type mice, and this mirrored the expression of Ii chain mRNA. Mice weaned
      onto an elemental diet did not exhibit Ii mRNA or increased CIITA mRNA in the
      intestinal epithelium by day 31, but low levels of Ii mRNA were detectable by day
      45. Of the 3 isoforms of CIITA, weaning onto a complex diet induced only CIITA IV
      by day 31. Mice deficient in the IFN-gamma receptor expressed Ia in the
      epithelium and they also accumulated Ii mRNA (at low levels) by day 45,
      irrespective of diet. CIITA III mRNA accumulation mirrored the dietary
      independent changes of Ii mRNA. CONCLUSIONS: Two mechanisms regulate Ii in the
      mouse intestinal epithelium: a rapid one, which is diet-induced acting through
      CIITA IV; and a slower, dietary-independent pathway, acting through CIITA III.

PMID- 15236187
TI  - Lymphotoxin beta receptor signaling induces the chemokine CCL20 in intestinal
      epithelium.
AB  - BACKGROUND & AIMS: The follicle-associated epithelium (FAE) that overlies Peyer's
      patches (PPs) exhibits distinct features compared with the adjacent villus
      epithelium. Besides the presence of antigen-sampling membranous M cells and the
      down-regulation of digestive functions, it constitutively expresses the chemokine
      CCL20. The mechanisms that induce FAE differentiation and CCL20 expression are
      poorly understood. The aim of this work was to test whether lymphotoxin beta
      receptor signaling (LTbetaR), which plays a central role in PPs' organogenesis,
      mediates CCL20 gene expression in intestinal epithelial cells. METHODS: CCL20,
      lymphotoxin beta (LTbeta) and LTbetaR expression were monitored during embryonic
      development by in situ hybridization of mouse intestine. The human intestinal
      epithelial cell line T84 was used to study CCL20 expression following
      LTalpha(1)/beta(2) stimulation. In vivo CCL20 expression following agonistic anti
      LTbetaR antibody treatment was studied by laser microdissection and quantitative
      RT-PCR. RESULTS: CCL20 was expressed in the FAE before birth at the time when the
      first hematopoietic CD4(+)CD3(-) appeared in the PP anlage. LTbetaR was expressed
      in the epithelium during PP organogenesis, making it a putative target for
      LTalpha(1)beta(2)signals. In vitro, CCL20 was induced in T84 cells upon LTbetaR
      signaling, either using an agonistic ligand or anti-LTbeta receptor agonistic
      antibody. LTalpha(1)beta(2)-induced CCL20 expression was found to be NF-kappaB
      dependent. LTbetaR signaling up-regulated CCL20 expression in the small
      intestinal epithelium in vivo. CONCLUSIONS: Our results show that LTbetaR
      signaling induces CCL20 expression in intestinal epithelial cells, suggesting
      that this pathway triggers constitutive production of CCL20 in the FAE.

PMID- 15236188
TI  - Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier
      integrity via protein kinase C.
AB  - BACKGROUND & AIMS: Protein kinase C (PKC) has been implicated in regulation of
      intestinal epithelial integrity in response to lumenal bacteria. Intestinal
      epithelial cells (IECs) constitutively express Toll-like receptor (TLR)2, which
      contains multiple potential PKC binding sites. The aim of this study was to
      determine whether TLR2 may activate PKC in response to specific ligands, thus
      potentially modulating barrier function in IECs. METHODS: TLR2 agonist (synthetic
      bacterial lipopeptide Pam(3)CysSK4, peptidoglycan)-induced activation of PKC
      related signaling cascades were assessed by immunoprecipitation, Western
      blotting, immunofluorescence, and kinase assays-combined with functional
      transfection studies in the human model IEC lines HT-29 and Caco-2.
      Transepithelial electrical resistance characterized intestinal epithelial barrier
      function. RESULTS: Stimulation with TLR2 ligands led to activation
      (phosphorylation, enzymatic activity, translocation) of specific PKC isoforms
      (PKCalpha and PKCdelta). Phosphorylation of PKC by TLR2 ligands was blocked
      specifically by transfection with a TLR2 deletion mutant. Ligand-induced
      activation of TLR2 greatly enhanced transepithelial resistance in IECs, which was
      prevented by pretreatment with PKC-selective antagonists. This effect correlated
      with apical tightening and sealing of tight junction (TJ)-associated ZO-1, which
      was mediated via PKC in response to TLR2 ligands, whereas morphologic changes of
      occludin, claudin-1, or actin cytoskeleton were not evident. Downstream the
      endogenous PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS),
      but not transcriptional factor activator protein-1 (AP-1), was activated
      significantly on stimulation. CONCLUSIONS: The present study provides evidence
      that PKC is an essential component of the TLR2 signaling pathway with the
      physiologic consequence of directly enhancing intestinal epithelial integrity
      through translocation of ZO-1 on activation.

PMID- 15236189
TI  - Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol
      induced murine cholesterol gallstones.
AB  - BACKGROUND & AIMS: Cholesterol gallstones are more common in women than men, and
      exposure to oral contraceptive steroids and conjugated estrogens increases the
      risk for gallstones. It is hypothesized that estrogen enhances cholesterol
      cholelithogenesis by augmenting functions of hepatic estrogen receptors (ERs).
      METHODS: To investigate molecular mechanisms of how estrogen influences
      cholesterol gallstones, we studied gonadectomized AKR/J mice of both genders that
      were implanted subcutaneously with pellets releasing 17beta-estradiol at 0, 3, or
      6 microg/day and that were fed a lithogenic diet for 12 weeks. To test the
      hypothesis that ERs play a pivotal role in mediating lithogenic actions of
      estrogen and to dissect the potential pathophysiologic roles of each receptor
      subtype, ERalpha and ERbeta, in the formation of gallstones, we investigated
      gonadectomized mice treated with synthetic ER subtype-selective agonists or
      antagonists. RESULTS: 17beta-estradiol promoted gallstone formation by up
      regulating hepatic expression of ERalpha but not ERbeta, and the lithogenic
      actions of estrogen can be blocked completely by the antiestrogenic ICI 182,780.
      The ERalpha-selective agonist propylpyrazole, but not the ERbeta-selective
      agonist diarylpropionitrile, augmented hepatic cholesterol output that resulted
      in cholesterol supersaturated bile and gallstones. Similar to the 17beta
      estradiol treatment, tamoxifen significantly increased biliary cholesterol
      secretion and gallstone prevalence in both gonadectomized females and males.
      CONCLUSIONS: The hepatic ERalpha, but not ERbeta, plays a critical role in 17beta
      estradiol-induced cholesterol gallstones. Our findings may offer a new approach
      to treat gallstones by inhibiting hepatic ER activity with a liver-specific,
      ERalpha-selective antagonist.

PMID- 15236190
TI  - Successful growth and characterization of mouse pancreatic ductal cells:
      functional properties of the Ki-RAS(G12V) oncogene.
AB  - BACKGROUND & AIMS: The Ki-RAS oncogene is altered in pancreatic ductal neoplasms.
      Pancreatic ductal cells (PDCs) were purified from cytokeratin 19 (K19)-Ki
      RAS(G12V) transgenic mice and control littermates to identify properties of Ki
      Ras activation in a cell-type-specific context. Because Ki-RAS mutation has
      prognostic significance in patients treated with radiation, we studied the
      influence of Ki-RAS status on radiation survival. METHODS: Pancreatic ductal
      fragments from mice with Ki-RAS(G12V) mutation or wild-type (WT)-Ki-RAS were
      cultured. Growth curves, electron microscopy, flow cytometry, and analysis of
      signaling and cell-cycle proteins were established. Farnesyltransferase inhibitor
      (FTI) treatment with R115777 before and after irradiation was used to determine
      the effect of Ki-Ras farnesylation on cell survival. RESULTS: PDCs from WT and
      K19-Ki-RAS(G12V) mice had features of ductal cells with formation of 3
      dimensional structures on collagen without differences in morphology, growth, and
      cell-cycle distribution. This may result from up-regulation of p16INK4 and
      p27(Kip1) and lack of hyperstimulation of the mitogen-activated protein kinase
      pathway in Ki-RAS(G12V) PDCs. No differences in radiation survival between Ki
      RAS(G12V) PDCs and WT PDCs were observed. However, Ki-RAS(G12V) PDCs expressing
      mutant p53(V143A) had enhanced survival compared with WT PDCs transduced with
      p53(V143A). R115777 treatment sensitized Ki-RAS(G12V) PDCs and Ki
      RAS(G12V)/p53(V143A) PDCs, but not WT PDCs. CONCLUSIONS: Novel characterization
      of murine WT PDCs and Ki-RAS(G12V) PDCs is described. Induction of cell-cycle
      regulators and lack of mitogen-activated protein kinase hyperstimulation likely
      are responsible for constraining activated Ki-RAS(G12V)-mediated proliferation.
      Because its activation was required for sensitization by an FTI, R115777 may be
      useful against pancreatic tumors expressing oncogenic Ki-Ras.

PMID- 15236191
TI  - Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis
      in Mdr2 (Abcb4) knockout mice.
AB  - BACKGROUND & AIMS: Because the mechanisms leading to bile duct damage in
      sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of
      bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(
      /-)) as a novel model of the disease. METHODS: Mdr2(-/-) and wild-type controls
      (Mdr2(+/+)) were studied at 2, 4, and 8 weeks of age. Liver histology,
      ultrastructure, immunofluorescence microscopy (to study inflammatory cells, tight
      junction protein ZO-1, basement membrane protein laminin, fluorescence-labeled
      ursodeoxycholic acid), immunohistochemistry (for alpha-smooth muscle actin,
      nitrotyrosine), sirius red staining, bacterial cultures of intra-abdominal
      organs, and polymerase chain reaction (PCR) for Helicobacter bilis DNA were
      compared between both genotypes. Hepatic cytokine expression was determined by
      reverse-transcription PCR. RESULTS: Bile ducts of Mdr2(-/-) showed disrupted
      tight junctions and basement membranes, bile acid leakage into portal tracts,
      induction of a portal inflammatory (CD11b, CD4-positive) infiltrate, and
      activation of proinflammatory (tumor necrosis factor [TNF]-alpha, interleukin
      [IL]-1beta) and profibrogenic cytokines (transforming growth factor [TGF]-beta1).
      This resulted in activation of periductal myofibroblasts, leading to periductal
      fibrosis, separating the peribiliary plexus from bile duct epithelial cells and,
      finally, causing atrophy and death of the bile duct epithelium. Bacterial
      translocation was not increased and H. bilis was not detectable in Mdr2(-/-).
      CONCLUSIONS: Sclerosing cholangitis in Mdr2(-/-) mice is a multistep process with
      regurgitation of bile from leaky ducts into the portal tracts, leading to
      induction of periductal inflammation, followed by activation of periductal
      fibrogenesis, finally causing obliterative cholangitis owing to atrophy and death
      of bile duct epithelial cells.

PMID- 15236192
TI  - Overexpression of heat shock protein Hsp27 protects against cerulein-induced
      pancreatitis.
AB  - BACKGROUND & AIMS: Heat shock protein (Hsp) 27 regulates actin cytoskeletal
      dynamics, and overexpression of Hsp27 in fibroblasts protects against stress in a
      phosphorylation-dependent manner. Induction of Hsps occurs in acute pancreatitis,
      but Hsp27 has not been ascribed a specific role. To examine whether Hsp27 would
      ameliorate acute pancreatitis, we generated transgenic mice overexpressing human
      Hsp27 (huHsp27) or Hsp27 with the phosphorylatable residues Ser(15,78,82) mutated
      to aspartic acid (huHsp27-3D) to mimic phosphorylation or to alanine (huHsp27
      3A), which is nonphosphorylatable. METHODS: huHsp27 was expressed at high levels
      in the exocrine pancreas by use of a cytomegalovirus promoter. Protein expression
      was analyzed by Western blotting and immunofluorescence. Acute pancreatitis was
      induced with 6 or 12 hourly cerulein injections (50 microg/kg intraperitoneally)
      and its severity assessed by measuring serum amylase and lipase levels,
      pancreatic trypsin activity, edema, and morphologic changes by quantitative
      scoring of multiple histologic sections and visualization of filamentous actin.
      Systemic inflammatory effects were monitored by measuring lung myeloperoxidase
      activity (a marker of neutrophil infiltration). RESULTS: huHsp27 protein was
      overexpressed in the pancreas and localized to pancreatic acini. Acute
      pancreatitis was ameliorated by overexpression of huHsp27 and the huHsp27-3D
      mutant, which were associated with suppression of pancreatic trypsin activity and
      acinar cell injury and preservation of the actin cytoskeleton. In contrast, these
      changes were unaffected by overexpression of the nonphosphorylatable huHsp27-3A
      mutant. CONCLUSIONS: Pancreatic overexpression of huHsp27 protects against
      cerulein-induced acute pancreatitis in a specific phosphorylation-dependent
      manner and is associated with preservation of the actin cytoskeleton.

PMID- 15236193
TI  - Chronic diarrhea.

PMID- 15236194
TI  - A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a
      gastrointestinal stromal tumor patient.
AB  - BACKGROUND & AIMS: Imatinib, a tyrosine kinase inhibitor of BCR-ABL, KIT, and
      platelet-derived growth factor receptor, is used in patients with chronic
      myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). Primary
      and acquired resistance to the drug can occur in both diseases. Molecular
      mechanisms have been reported in CML and GIST for primary resistance, whereas
      extensive studies on the mechanisms responsible for secondary resistance have
      been almost exclusively reported for CML. METHODS: In a patient with advanced
      GIST undergoing imatinib therapy, an isolated progressing peritoneal mass was
      excised, along with 2 still-responding lesions. Complementary DNA and genomic DNA
      were analyzed by sequencing for c-Kit gene mutations. KIT receptor expression and
      phosphorylation status were assessed by immunoprecipitation and Western blot.
      Transient-transfection experiments were performed with mutagenized KIT
      constructs, and their activation status was assessed. RESULTS: In addition to an
      exon 11 mutation, shared among all of the analyzed lesions, a novel point
      mutation in c-Kit exon 14 resulting in T670I substitution was found only in the
      progressing lesion, which harbored a phosphorylated receptor, as opposed to the
      finding of an inactive receptor in responding lesions. Functional analyses showed
      that KIT/T670I is insensitive to imatinib and that T670I mutation, introduced in
      a receptor responding to imatinib, subverted its sensitivity to the drug.
      CONCLUSIONS: This new mutation was confined to the progressing lesion; the
      resulting amino acidic substitution, T670I, affecting the ATP/imatinib pocket of
      KIT, makes it insensitive to the drug. Interestingly, this substitution is a
      homologue to the T315I mutation already reported in CML, where it is responsible
      for acquired resistance to imatinib.

PMID- 15236195
TI  - Gastrointestinal dendritic cells play a role in immunity, tolerance, and disease.
AB  - Discrimination between beneficial commensal organisms and potentially harmful
      pathogens is a central component of the essential role that gut immune cells play
      in maintaining the balance between immune activation and tolerance. Antigen
      presenting cells (APC) are the key to this process, and the type of APC,
      including epithelial cells, B cells, macrophages, and dendritic cells (DC), in
      the gut is varied. The purpose of this review is to focus on the vast amount of
      data that has recently been generated on gastrointestinal dendritic cells in the
      context of their potential function and contribution to mucosal immunity,
      tolerance, and disease.

PMID- 15236196
TI  - A critical review of the diagnosis and management of Barrett's esophagus: the AGA
      Chicago Workshop.
AB  - BACKGROUND & AIMS: The diagnosis and management of Barrett's esophagus (BE) are
      controversial. We conducted a critical review of the literature in BE to provide
      guidance on clinically relevant issues. METHODS: A multidisciplinary group of 18
      participants evaluated the strength and the grade of evidence for 42 statements
      pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each
      member anonymously voted to accept or reject statements based on the strength of
      evidence and his own expert opinion. RESULTS: There was strong consensus on most
      statements for acceptance or rejection. Members rejected statements that
      screening for BE has been shown to improve mortality from adenocarcinoma or to be
      cost-effective. Contrary to published clinical guidelines, they did not feel that
      screening should be recommended for adults over age 50, regardless of age or
      duration of heartburn. Members were divided on whether surveillance prolongs
      survival, although the majority agreed that it detects curable neoplasia and can
      be cost-effective in selected patients. The majority did not feel that acid
      reduction therapy reduces the risk of esophageal adenocarcinoma but did agree
      that nonsteroidal antiinflammatory drugs are associated with a cancer risk
      reduction and are of promising (but unproven) value. Participants rejected the
      notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE
      but agreed that this may be an appropriate strategy in a subgroup of patients
      with high-grade dysplasia. CONCLUSIONS: Based on this review of BE, the opinions
      of workshop members on issues pertaining to screening and surveillance are at
      variance with published clinical guidelines.

PMID- 15236204
TI  - Understanding familial colorectal cancer-finding the corner pieces and filling in
      the center of the puzzle.

PMID- 15236205
TI  - Out, out darn toxin: the role of MDR in intestinal homeostasis.

PMID- 15236206
TI  - Aspirin in the XXI century: its major clinical impact, novel mechanisms of
      action, and new safer formulations.

PMID- 15236207
TI  - Eradication of Helicobacter pylori as a means towards eliminating gastric
      adenocarcinoma.

PMID- 15236208
TI  - Stem cells and liver disease: promise laced with confusion and intrigue.

PMID- 15236209
TI  - Prevention of post-ERCP pancreatitis: are there any pearls for sale?

PMID- 15236211
TI  - Is there a role for octreotide, a somatostatin analog, in the treatment of
      functional GI disorders?

PMID- 15236212
TI  - SBP and the pathogenesis of renal failure-the hidden triangle.

PMID- 15236217
TI  - Sclerotherapy versus vasoactive drugs: are all meta-analyses the same?

PMID- 15236219
TI  - Is diabetes a risk factor for hepatocellular carcinoma?

PMID- 15236221
TI  - Low-grade dysplasia in ulcerative colitis: natural history data still unknown.

PMID- 15236223
TI  - Response to Straumann et al.: primary eosinophilic esophagitis.

PMID- 15236225
TI  - Crohn's disease is associated with a toll-like receptor-9 polymorphism.

PMID- 15236226
TI  - Discussion on toll-like receptor 9 signaling mediates the anti-inflammatory
      effects of probiotics in murine experimental colitis.

PMID- 15236231
TI  - Cerebellar Purkinje cell loss in aging Hu-Bcl-2 transgenic mice.
AB  - The number of cerebellar Purkinje cells is increased by over 40% in young
      transgenic mice that overexpress a human Bcl-2 transgene (Hu-Bcl-2). To determine
      whether the Bcl-2-mediated rescue of Purkinje cells persists through life, the
      numbers of Purkinje cells were estimated in 6-, 12-, 18-, and 24-month-old Hu-Bcl
      2 transgenic mice and age-matched controls. In addition, the expression of four
      markers for Purkinje cell differentiation, calbindin (CaBP), the 67-kDa isoform
      of glutamic acid decarboxylase (GAD67), gamma-aminobutyric acid transaminase
      (GABA-T), and the NMDA-R1 receptor subtype (NMDA-NR1) was analyzed in 6-month-old
      Hu-Bcl-2 transgenics and controls to determine whether overexpression of Bcl-2
      and rescue from naturally occurring cell death affects the normal differentiation
      of Purkinje cells. The estimates of Purkinje cell numbers showed that the number
      of Purkinje cells in the Hu-Bcl-2 transgenics declines after 6 months to approach
      wild-type values by 18 months. Although the exogenous human BCL-2 is still
      expressed in Purkinje cells at 24 months, the expression levels of human BCL-2
      appear to decline significantly after 6 months, suggesting that survival of the
      supernumary Purkinje cells depends on the sustained overexpression of Bcl-2. All
      the Purkinje cells in the Hu-Bcl-2 transgenic mice appeared to express normal
      levels of the differentiation markers analyzed so there was no evidence for a
      class of Purkinje cells that do not differentiate normally when rescued from
      naturally occurring cell death.

PMID- 15236232
TI  - Cyto- and chemoarchitecture of the cerebral cortex of the Australian echidna
      (Tachyglossus aculeatus). I. Areal organization.
AB  - We have examined the topography of the cerebral cortex of the Australian echidna
      (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for
      parvalbumin, calbindin, and nonphosphorylated neurofilament protein (SMI-32
      antibody), and histochemistry for acetylcholinesterase (AChE) and NADPH
      diaphorase. Myelinated fibers terminating in layer IV of the cortex were abundant
      in the primary sensory cortical areas (areas S1, R, and PV of somatosensory
      cortex; primary visual cortex) as well as the frontal cortex. Parvalbumin
      immunoreactivity was particularly intense in the neuropil and somata of
      somatosensory regions (S1, R, and PV areas) but was poor in motor cortex.
      Immunoreactivity with the SMI-32 antibody was largely confined to a single
      sublayer of layer V pyramidal neurons in discrete subregions of the
      somatosensory, visual, and auditory cortices, as well as a large field in the
      frontal cortex (Fr1). Surprisingly, SMI-32 neurons were absent from the motor
      cortex. In AChE preparations, S1, R, V1, and A regions displayed intense
      reactivity in supragranular layers. Our findings indicate that there is
      substantial regional differentiation in the expanded frontal cortex of this
      monotreme. Although we agree with many of the boundaries identified by previous
      authors in this unusual mammal (Abbie [1940] J. Comp. Neurol. 72:429-467), we
      present an updated nomenclature for cortical areas that more accurately reflects
      findings from functional and chemoarchitectural studies.

PMID- 15236230
TI  - Expression of calcium transporters in the retina of the tiger salamander
      (Ambystoma tigrinum).
AB  - Changes in intracellular calcium concentration, [Ca2+]i, modulate the flow of
      visual signals across all stages of processing in the retina, yet the identities
      of Ca2+ transporters responsible for these changes are still largely unknown. In
      the current study, the distribution of plasma membrane and intracellular Ca2+
      transporters in the retina of tiger salamander, a model system for physiological
      studies of retinal function, was determined. Plasma membrane calcium ATPases
      (PMCAs), responsible for high-affinity Ca2+ extrusion, were highly expressed in
      the salamander retina. PMCA isoforms 1, 2, and 4 were localized to
      photoreceptors, whereas the inner retina expressed all four isoforms. PMCA3 was
      expressed in a sparse population of amacrine and ganglion neurons, whereas PMCA2
      was expressed in most amacrine and ganglion cells. Na+/Ca2+ exchangers, a high
      capacity Ca2+ extrusion system, were expressed in the outer plexiform layer and
      in a subset of inner nuclear and ganglion layer cells. Intracellular Ca2+ store
      transporters were also represented prominently. SERCA2a, a splice variant of the
      sarcoplasmic-endoplasmic Ca2+ ATPase, was found mostly in photoreceptors, whereas
      SERCA2b was found in the majority of retinal neurons and in glial cells. The
      predominant endoplasmic reticulum (ER) Ca2+ channels in the salamander retina are
      represented by the isoform 2 of the IP3 receptor family and the isoform 2 of the
      ryanodine receptor family. These results indicate that Ca2+ transporters in the
      salamander retina are expressed in a cell type-specific manner.

PMID- 15236233
TI  - Immunocytochemical localization of three vesicular glutamate transporters in the
      cat retina.
AB  - Vesicular transporters play an essential role in the packaging of glutamate for
      synaptic release and so are of particular importance in the retina, where
      glutamate serves as the neurotransmitter for photoreceptors, bipolar cells, and
      ganglion cells. In the present study, we have examined the distribution of the
      three known isoforms of vesicular glutamate transporter (VGLUT) in the cat
      retina. VGLUT1 was localized to all photoreceptor and bipolar cells, whereas
      VGLUT2 was found in ganglion cells. This basic pattern of complementary
      distribution for the two transporters among known populations of glutamatergic
      cells is similar to previous findings in the brain and spinal cord. However, the
      axon terminals of S-cone photoreceptors were found to express both VGLUT1 and
      VGLUT2 and some ganglion cells labeled for both VGLUT2 and VGLUT3. Such
      colocalizations suggest the existence of dual modes of regulation of vesicular
      glutamate transport in these neurons. Staining for VGLUT2 was also present in a
      small number of varicose processes, which were seen to ramify throughout the
      inner plexiform layer. These fibers may represent axon collaterals of ganglion
      cells. The most prominent site of VGLUT3 immunoreactivity was in a population of
      amacrine cells; the axon terminals of B-type horizontal cells were also labeled
      at their contacts with rod spherules. The presence of the VGLUT3 transporter at
      sites not otherwise implicated in glutamate release may indicate novel modes of
      glutamate signaling or additional roles for the transporter molecule.

PMID- 15236234
TI  - Form and function in the unique inner ear of a teleost: the silver perch
      (Bairdiella chrysoura).
AB  - Members of the teleost family Sciaenidae show significant variation in inner ear
      and swim bladder morphology as well as in the relationship between the swim
      bladder and the inner ear. In the silver perch (Bairdiella chrysoura), a
      Stellifer-group sciaenid, both the saccular and utricular otoliths are enlarged
      relative to those in other teleosts. Additionally, its swim bladder is two
      chambered, and the anterior chamber surrounds the otic capsule and terminates
      lateral to the saccules. Structure and function of the auditory system of the
      silver perch were explored by using gross dissections, scanning electron
      microscopy, CT scan reconstruction, and auditory brainstem response approach.
      Several morphological specializations of the auditory system of the silver perch
      were found, including expansion of the utricular and lagenar otoliths, close
      proximity between the saccules and the utricles, deeply grooved sulci on the
      saccular otoliths, two-planar saccular sensory epithelia, and a unique
      orientation pattern of sensory hair cell ciliary bundles on the saccular sensory
      epithelium. It was determined that the silver perch can detect up to 4 kHz, with
      lowest auditory thresholds between 600 Hz and 1 kHz. Audition in the silver perch
      is comparable to that in the goldfish (Carassius auratus), a hearing
      "specialist." The morphological specializations of the inner ear and swim bladder
      of the silver perch may be linked to its enhanced hearing capabilities. The
      findings of this study support the proposal that sciaenids are excellent model
      species for investigating structure-function relations in the teleost auditory
      system.

PMID- 15236235
TI  - Expression and regulation of an FMRFamide-related neuropeptide gene family in
      Caenorhabditis elegans.
AB  - FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides (FaRPs) have been found
      throughout the animal kingdom, where they are involved in many behaviors. We
      previously identified 22 genes comprising the flp gene family that encodes FaRPs
      in Caenorhabditis elegans; in this paper we report the identification of another
      flp gene, flp-23. As a first step toward determining their functional roles in C.
      elegans, we examined the cell-specific expression pattern of the flp gene family.
      Of the 19 flp genes examined, each gene is expressed in a distinct set of cells;
      these cells include interneurons, motor neurons, and sensory neurons that are
      involved in multiple behaviors, as well as supporting cells, muscle cells, and
      epidermal cells. Several flp genes show sex-specific expression patterns.
      Furthermore, we find that expression of two flp genes changes in response to the
      developmental state of the animal. Many neurons express multiple flp genes. To
      investigate how flp genes are regulated in different neuronal subtypes, we
      examined flp expression in a small, well-defined subset of neurons, the
      mechanosensory neurons. Mutations in the unc-86 and mec-3 genes, which are
      necessary for the production and differentiation of the mechanosensory neurons,
      result in the complete loss of flp-4, flp-8, and flp-20 expression in
      mechanosensory neurons. Collectively, these data indicate that members of the flp
      gene family are likely to influence multiple behaviors and that their regulation
      can be dependent on the developmental state of the organism.

PMID- 15236236
TI  - The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with
      glutamate receptor complexes at rat retinal synapses.
AB  - The postsynaptic density (PSD) at glutamatergic synapses is a macromolecular
      complex of various molecules that organize the different glutamate receptors
      spatially and link them to their appropriate downstream signaling pathways and to
      the cytoskeleton. Recently, a new family of multidomain proteins called Shanks or
      ProSAPs (proline-rich synapse-associated proteins) has been identified. They are
      suggested to be central adaptor proteins of the PSD of glutamatergic synapses,
      bridging different types of glutamate receptor complexes. With
      immunocytochemistry and light and electron microscopy, we examined the cellular,
      synaptic, and postnatal developmental expression of ProSAP1/Shank2 at the
      synapses of rat retina. With double-labeling experiments and confocal microscopy,
      we analyzed the association of ProSAP1/Shank2 with proteins specific for
      glutamatergic, glycinergic, and gamma-aminobutyric acid (GABA)ergic synapses and
      with proteins known to be involved in the structural and functional organization
      of PSDs containing N-methyl-D-aspartate receptors [95-kDa postsynaptic density
      protein (PSD-95)], group I metabotropic glutamate receptors (Homer1), and alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors [glutamate
      receptor-interacting protein (GRIP)]. ProSAP1/Shank2 was present postsynaptically
      at the glutamatergic ribbon synapses of photoreceptor and bipolar cells, and it
      was absent from glycinergic and GABAergic amacrine cell synapses. The double
      labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2
      with Homer1 and PSD-95, and little colocalization with GRIP. These data suggest
      that ProSAP1/Shank2 acts as an organizer at PSDs of different glutamatergic
      retinal synapses.

PMID- 15236237
TI  - Location of preganglionic neurons is independent of birthdate but is correlated
      to reelin-producing cells in the spinal cord.
AB  - Many studies suggest that during neuronal development the birthdate of a neuron
      appears to have significant consequences for its ultimate location and identity.
      Our past study shows that sympathetic preganglionic neurons (SPN) in mice lacking
      the reelin gene settle in abnormal positions in the spinal cord. In the present
      study we determined that birthdate is not a factor contributing to the abnormal
      position of SPN in reeler. In both normal and reeler mice the period of
      neurogenesis of SPN was similar, and the final location of SPN in the spinal cord
      was independent of birthdate. Additionally, we have identified at least two types
      of ventral interneurons, V1 and V2, that are involved in the production of Reelin
      and the positioning of SPN in the spinal cord.

PMID- 15236238
TI  - Effects of spinal nerve ligation on immunohistochemically identified neurons in
      the L4 and L5 dorsal root ganglia of the rat.
AB  - This study examined the effect of spinal nerve ligation on different populations
      of immunohistochemically identified neurons in the dorsal root ganglia (DRG) of
      the rat. The optical fractionator method was used to count neurons in the
      ipsilateral L4 and L5 DRG 1-20 weeks after ligation of the L5 and L6 spinal
      nerves, sham surgery, or no surgery. One week after ligation, neurons in the L5
      DRG that were labeled by IB4, a marker of unmyelinated primary afferent neurons,
      were largely absent. The numbers of IB4-labeled neurons then progressively
      increased to reach control values by 20 weeks. A smaller, sustained decrease
      occurred in the number of small-, medium- and large-sized neurons immunoreactive
      for calcitonin gene-related peptide (CGRP), a marker for peptidergic primary
      afferents, in the L5 DRG. There was a proportionately greater decrease in the
      numbers of medium- to large-sized CGRP-like immunoreactive neurons. The number of
      myelinated afferents in the L5 DRG, identified by their staining for
      neurofilament protein (N52), did not change after ligation. However, closer
      examination revealed a significant decrease in the numbers of large-sized
      neurons, coupled with an increase in the numbers of small- to medium-sized
      neurons, and the appearance of a novel population of very small-sized neurons
      labeled by N52. The numbers and cell size distributions of IB4-labeled, CGRP-like
      immunoreactive, and N52-labeled neurons were unchanged in the adjacent L4 DRG.
      Unlike the L5 DRG, injury-induced changes in the expression of various receptors,
      neurotransmitters and neurotrophic factors in the L4 DRG are not confounded by a
      change in the immunohistochemical phenotype of primary afferent neurons.

PMID- 15236239
TI  - Changes in galanin immunoreactivity in rat lumbosacral spinal cord and dorsal
      root ganglia after spinal cord injury.
AB  - Alterations in the expression of the neuropeptide galanin were examined in
      micturition reflex pathways 6 weeks after complete spinal cord transection (T8).
      In control animals, galanin expression was present in specific regions of the
      gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including:
      (1) the dorsal commissure; (2) the superficial dorsal horn; (3) the regions of
      the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus
      (L6-S1); and (4) the lateral collateral pathway in lumbosacral spinal segments.
      Densitometry analysis demonstrated significant increases (P < or = 0.001) in
      galanin immunoreactivity (IR) in these regions of the S1 spinal cord after spinal
      cord injury (SCI). Changes in galanin-IR were not observed at the L4-L6 segments
      except for an increase in galanin-IR in the dorsal commissure in the L4 segment.
      In contrast, decreases in galanin-IR were observed in the L1 segment. The number
      of galanin-IR cells increased (P < or = 0.001) in the L1 and S1 dorsal root
      ganglia (DRG) after SCI. In all DRG examined (L1, L2, L6, and S1), the percentage
      of bladder afferent cells expressing galanin-IR significantly increased (4-19
      fold) after chronic SCI. In contrast, galanin expression in nerve fibers in the
      urinary bladder detrusor and urothelium was decreased or eliminated after SCI.
      Expression of the neurotrophic factors nerve growth factor (NGF) and brain
      derived neurotrophic factor (BDNF) was altered in the spinal cord after SCI. A
      significant increase in BDNF expression was present in spinal cord segments after
      SCI. In contrast, NGF expression was only increased in the spinal segments
      adjacent and rostral to the transection site (T7-T8), whereas spinal segments
      (T13-L1; L6-S1), distal to the transection site exhibited decreased NGF
      expression. Changes in galanin expression in micturition pathways after SCI may
      be mediated by changing neurotrophic factor expression, particularly BDNF. These
      changes may contribute to urinary bladder dysfunction after SCI.

PMID- 15236240
TI  - Bilateral effects of spinal overhemisections on the development of the
      somatosensory system in rats.
AB  - Connections of the forepaw regions of somatosensory cortex (S1) were determined
      in rats reared to maturity after spinal cord overhemisections at cervical level
      C3 on postnatal day 3. Overhemisections cut all ascending and descending pathways
      and intervening gray on one side of the spinal cord and the pathways of the
      dorsal funiculus contralaterally. Bilateral lesions of the dorsal columns reduced
      the size of the brainstem nuclei by 41%, and the ventroposterior lateral
      subnucleus (VPL) of the thalamus by 20%. Bilateral lesions also prevented the
      emergence of the normal cytochrome oxidase barrel pattern in forepaw and hindpaw
      regions of S1. Injections of wheat germ agglutinin conjugated to horseradish
      peroxidase were placed in the forepaw region of granular S1 and surrounding
      dysgranular S1 contralateral to the hemisection. The VPL nucleus was densely
      labeled, whereas the adjoining ventroposterior medial subnucleus, VPM,
      representing the head, was unlabeled. Thus, there was no evidence of abnormal
      connections of VPM to forepaw cortex. Foci of transported label in the
      ipsilateral hemisphere appeared to be in normal locations and of normal extents,
      but connections in the opposite hemisphere were broadly and nearly uniformly
      distributed in sensorimotor cortex in a pattern similar to that in postnatal
      rats. Rats with incomplete lesions that spared the dorsal column pathway on the
      left side but not the right demonstrated surprisingly normal distributions of
      callosal connections in the nondeprived right hemisphere, even though the
      injected left hemisphere was deprived. Thus, the development of the normal
      pattern of callosal connections depends on dorsal column input and not on normal
      interhemsipheric interactions.

PMID- 15236241
TI  - Identification and characterization of Cu(2)O- and ZnO-binding polypeptides by
      Escherichia coli cell surface display: toward an understanding of metal oxide
      binding.
AB  - We have used the FliTrx cell surface display system to identify disulfide
      constrained dodecapeptides binding to the semiconducting metal oxides Cu(2)O and
      ZnO. Sequence analysis of the inserts revealed that the two populations exhibit
      similar, yet subtly different patterns of amino acid usage. Both sets of binders
      were enriched in arginine, tryptophan, and glycine with a higher degree of
      positional preference in the case of Cu(2)O binders. Tyrosine, proline, and
      serine were underrepresented in both populations. Peptides binding
      electrodeposited Cu(2)O or ZnO with high avidity could be subdivided into two
      classes based on pI and hydrophilicity. In the hydrophilic and positively charged
      Class I binders, the Arg-X-X-Arg tetrapeptide appears to be implicated in metal
      oxide binding, whereas Arg-Arg and Arg-Lys pairs allow for discrimination between
      Cu(2)O and ZnO. Molecular dynamics simulations of the disulfide-constrained
      peptides suggest that the aforementioned motifs are important to properly orient
      two basic residues that are likely to contact the metal oxides. The implications
      of our results in understanding the rules governing the interaction between
      peptides and inorganic compounds and in their use for the design of hybrid
      nanoarchitectures are discussed.

PMID- 15236242
TI  - Fibroblast growth and H-7 protein kinase inhibitor response monitored in
      microimpedance sensor arrays.
AB  - Functional genomic studies and drug candidate testing both require high
      throughput, parallel experimentation strategies to screen for variable cellular
      behaviors. In this article we describe the use of an impedance sensing electrode
      array that is capable of sensing cell "presence" as well as the extent of cell
      (focal) attachment to the substrate. The signals provided by mouse fibroblasts on
      a sensing structure containing four different sized electrodes are reported. In
      the absence of cells, each electrode's impedance was found to depend as expected
      on electrode size and frequency. The impedance increased by several-fold when
      fibroblasts attached and spread out over time. More notably, the sensors also
      detected the cellular response to the protein kinase C inhibitor, H-7. H-7
      inhibits actomyosin contractility; thereafter, the loss of focal adhesion
      complexes occurs. The sensors, in turn, detected an impedance decrease after H-7
      addition and an increase in impedance after H-7 removal.

PMID- 15236243
TI  - Optimization of polyhydroxybutyrate production by mixed cultures submitted to
      aerobic dynamic feeding conditions.
AB  - Activated sludge submitted to aerobic dynamic feeding conditions showed a good
      and stable capacity to store polyhydroxybutyrate (PHB). The system, working for 2
      years, selected a microbial population with a high PHB storage capacity. The
      influence of carbon and nitrogen concentrations on the PHB accumulation yield was
      studied in a range of 15-180 Cmmol/l for acetate and 0-2.8 Nmmol/l for ammonia.
      Low ammonia concentrations favored PHB accumulation. The maximum PHB content,
      67.5%, was obtained for 180 Cmmol/l of acetate supplied in one pulse. However,
      such high substrate concentration proved to be inhibitory for the storage
      mechanism, causing a slowdown of the specific PHB storage rate. In order to avoid
      substrate inhibition, 180 Cmmol/l of acetate was supplied in different ways:
      continuously fed and in three pulses of 60 Cmmol/l each. In both cases the
      specific PHB storage rate increased and the PHB content obtained were 56.2% and
      78.5%, respectively. The latter value of PHB content is similar to that obtained
      by pure cultures and was never reported for mixed cultures. Addition of acetate
      by pulses controlled by the oxygen concentration was kept for 16 days, the PHB
      content being always above 70% of cell dry weight.

PMID- 15236244
TI  - Synergistic activity of Paenibacillus sp. BP-23 cellobiohydrolase Cel48C in
      association with the contiguous endoglucanase Cel9B and with endo- or exo-acting
      glucanases from Thermobifida fusca.
AB  - Cellobiohydrolase Cel48C from Paenibacillus sp. BP-23, an enzyme displaying
      limited activity on most cellulosic substrates, was assayed for activity in the
      presence of other bacterial endo- or exocellulases. Significant enhanced activity
      was observed when Cel48C was incubated in the presence of Paenibacillus sp. BP-23
      endoglucanase Cel9B or Thermobifida fusca cellulases Cel6A and Cel6B, indicating
      that Cel48C acts synergistically with them. Maximum synergism rates on bacterial
      microcrystalline cellulose or filter paper were obtained with a mixture of
      Paenibacillus cellulases Cel9B and Cel48C, accompanied by T. fusca exocellulase
      Cel6B. Synergism was also observed in cell extracts from recombinant clone E.
      coli pUCel9-Cel48 expressing the two contiguous Paenibacillus cellulases Cel9B
      and Cel48C. The enhanced cellulolytic activity displayed by the cellulase
      mixtures assayed could be used as an efficient tool for biotechnological
      applications like pulp and paper manufacturing.

PMID- 15236245
TI  - Detection of alkanes, alcohols, and aldehydes using bioluminescence.
AB  - We report a novel method for the rapid, sensitive, and quantitative detection of
      alkanes, alcohols, and aldehydes that relies on the reaction of bacterial
      luciferase with an aldehyde, resulting in the emission of light. Primary alcohols
      with corresponding aldehydes that are within the substrate range of the
      particular luciferase are detected after conversion to the aldehyde by an alcohol
      dehydrogenase. In addition, alkanes themselves may be detected by conversion to
      primary alcohols by an alkane hydroxylase, followed by conversion to the aldehyde
      by alcohol dehydrogenase. We developed a rapid bioluminescent method by
      genetically engineering the genes encoding bacterial luciferase, alcohol
      dehydrogenase, and alkane hydroxylase into a plasmid for simultaneous expression
      in an E. coli host cell line. Alkanes, alcohols, or aldehydes were detected
      within seconds, with sensitivity in the micromolar range, by measuring the
      resulting light emission with a microplate reader. We demonstrate the application
      of this method for the detection of alkanes, alcohols, and aldehydes and for the
      detection of alkane hydroxylase and alcohol dehydrogenase activity in vivo. This
      method is amenable to the high-throughput screening needs required for the
      identification of novel catalysts.

PMID- 15236246
TI  - Enabling multienzyme biocatalysis using nanoporous materials.
AB  - Multistep reactions catalyzed by a covalently immobilized enzyme-cofactor-enzyme
      system were achieved. Lactate dehydrogenase (LDH), glucose dehydrogenase (GDH),
      and cofactor NADH were incorporated into two porous silica glass supports. One of
      the glass supports had pores of 30 nm in diameter, while the other was of 100-nm
      pore size. Effective shuttling of the covalently bound NADH between LDH and GDH
      was achieved, such that regeneration cycles of NADH/NAD(+) were observed. The
      glass of 30-nm pore size afforded enzyme activities that were about twice those
      observed for the glass of 100-nm pore size, indicating the former provided better
      enzyme-cofactor integration. The effect of the size of spacers was also examined.
      The use of longer spacers increased the reaction rates by approximately 18 times
      as compared to those achieved with glutaraldehyde linkage. It appeared that the
      concave configuration of the nanopores played an important role in enabling the
      multistep reactions. The same multienzyme system immobilized on nonporous
      polystyrene particles of 500-nm diameter was only approximately 2% active as the
      glass-supported system. It is believed that the nanoporous structure of the glass
      supports enhances the molecular interactions among the immobilized enzymes and
      cofactor, thus improving the catalytic efficiency of the system.

PMID- 15236247
TI  - Development of image analysis techniques as a tool to detect and quantify
      morphological changes in anaerobic sludge: I. Application to a granulation
      process.
AB  - Image analysis techniques were developed and applied to quantify the process of
      anaerobic granulation in an expanded granular sludge blanket reactor (EGSB) fed
      with a synthetic substrate based on glucose [60-30% COD (chemical oxygen demand)]
      and volatile fatty acids (40-70% COD) over 376 days. In a first operation period
      that lasted 177 days, the aggregation of dispersed sludge was quantitatively
      monitored through the recognition and quantification of aggregates and filaments.
      A parameter defined as the ratio between the filaments' length and the aggregates
      projected area (LfA) has proven to be sensitive to detect changes in the
      aggregation status of the anaerobic sludge. The aggregation time-defined as the
      moment when a balance between filaments' length and aggregates' size was
      established-was recognized through the LfA. The percentage of projected area of
      aggregates within three size ranges (0.01-0.1 mm, 0.1-1 mm, and >1 mm, equivalent
      diameter) reflected the granular size spectrum during the aggregation process.
      When sudden increases on the upflow velocity and on the organic loading rate were
      applied to the previously formed granules, the developed image analysis
      techniques revealed to be good indicators of granular sludge stability, since
      they were sensitive to detected filaments release, fragmentation, and erosion
      that usually leads to washout. The specific methanogenic activities in the
      presence of acetate, propionate, butyrate, and H(2)/CO(2) increased along the
      operation, particularly relevant was the sudden increase in the specific
      hydrogenophilic activity, immediately after the moment recognized as aggregation
      time.

PMID- 15236248
TI  - Development of image analysis techniques as a tool to detect and quantify
      morphological changes in anaerobic sludge: II. Application to a granule
      deterioration process triggered by contact with oleic acid.
AB  - Image analysis techniques are applied to monitor the morphological changes in
      granular sludge present in an expanded granular sludge blanket (EGSB) reactor fed
      with oleic acid. Deterioration of granular sludge was monitored along the trial
      period by measuring the percentage of aggregates smaller than 1 mm (in terms of
      Feret diameter) either in terms of projected area or in terms of number of
      aggregates. A good correlation was obtained between these values and the
      percentage of aggregates smaller than 1 mm were physically sorted and quantified
      by the volatile suspended solid content. The ratio of total filaments length to
      cross-sectional area of aggregates defined as LfA, was applied to quantify the
      dispersion level of the granular sludge, which increased until day 141 and
      remained almost invariant afterwards. LfA was sensitive to the sludge
      deterioration process and was able to indicate, with the anticipation of about 1
      month, the most significant biomass washout episode that occurred in the trial
      period. A mechanism of filaments' release, detachment and selective washout was
      proposed to explain the action of LfA from this viewpoint. The equivalent
      diameter of the bottom aggregates larger than 1 mm increased with the increase on
      the amount of long chain fatty acids associated with the biomass by mechanisms of
      adsorption, precipitation, or entrapment. After a threshold value of about 200 mg
      COD-LCFA gVSS (COD = chemical oxygen demand; LCFA = long chain fatty acids; VSS =
      volatile suspended solids), a migration of granular sludge from the bottom to a
      top-floating layer was evident.

PMID- 15236249
TI  - Mono and diterpene production in Escherichia coli.
AB  - Mono- and diterpenoids are of great industrial and medical value as specialty
      chemicals and pharmaceuticals. Production of these compounds in microbial hosts,
      such as Escherichia coli, can be limited by intracellular levels of the
      polyprenyl diphosphate precursors, geranyl diphosphate (GPP), and geranylgeranyl
      diphosphate (GGPP). To alleviate this limitation, we constructed synthetic
      operons that express three key enzymes for biosynthesis of these precursors: (1).
      DXS,1-deoxy-d-xylulose-5-phosphate synthase; (2). IPPHp, IPP isomerase from
      Haematococcus pluvialis; and (3). one of two variants of IspA, FPP synthase that
      produces either GPP or GGPP. The reporter plasmids pAC-LYC and pACYC-IB, which
      encode enzymes that convert either FPP or GGPP, respectively, to the pigment
      lycopene, were used to demonstrate that at full induction, the operon encoding
      the wild-type FPP synthase and mutant GGPP synthase produced similar levels of
      lycopene. To synthesize di- or monoterpenes in E. coli using the GGPP and GPP
      encoding operons either a diterpene cyclase [casbene cyclase (Ricinus communis L)
      and ent-kaurene cyclase (Phaeosphaeria sp. L487)] or a monoterpene cyclase [3
      carene cyclase (Picea abies)] was coexpressed with their respective precursor
      production operon. Analysis of culture extracts or headspace by gas
      chromatography-mass spectrometry confirmed the in vivo production of the
      diterpenes casbene, kaur-15-ene, and kaur-16-ene and the monoterpenes alpha
      pinene, myrcene, sabinene, 3-carene, alpha-terpinene, limonene, beta
      phellandrene, alpha-terpinene, and terpinolene. Construction and functional
      expression of GGPP and GPP operons provides an in vivo precursor platform host
      for the future engineering of di- and monoterpene cyclases and the overproduction
      of terpenes in bacteria.

PMID- 15236250
TI  - Kinetic studies on the aggregation of Aspergillus niger conidia.
AB  - Morphology has a crucial effect on productivity and the supply of substrate for
      cultures of filamentous fungi. However, cultivation parameters leading to the
      desired morphology are often chosen empirically as the mechanisms governing the
      processes involved are usually unknown. For coagulating microorganisms like
      Aspergillus niger the morphological development is considered to start with the
      aggregation of conidia right after inoculation. To elucidate the mechanism of
      this process, kinetic studies were carried out using an in-line particle size
      analyzer. Based on the data obtained from these experiments a model for conidial
      aggregation is proposed in this article. It consists of two separate aggregation
      steps. The first one takes place immediately after inoculation, but only leads to
      a small decrease of total particle concentration. Most suspended conidia
      aggregate after a second aggregation step triggered by germination and hyphal
      growth. Aggregation velocity of this second phase is linearly dependent on the
      particle growth rate.

PMID- 15236251
TI  - Process development for degradation of phenol by Pseudomonas putida in hollow
      fiber membrane bioreactors.
AB  - The degradation of phenol (100-2800 mg/L) by cells Pseudomonas putida CCRC14365
      in an extractive hollow-fiber membrane bioreactor (HFMBR) was studied, in which
      the polypropylene fibers were prewetted with ethanol. The effects of flow
      velocity, the concentrations of phenol, and the added dispersive agent
      tetrasodium pyrophosphate on phenol degradation and cell growth were examined. It
      was shown that about 10% of phenol was sorbed on the fibers at the beginning of
      the degradation process. The cells P. putida fully degraded 2000 mg/L of phenol
      within 73 h when the cells were immobilized and separated by the fibers. Even at
      a level of 2800 mg/L, phenol could be degraded more than 90% after 95-h
      operation. At low phenol levels (< 400 mg/L) where substrate inhibition was not
      severe, it was more advantageous to treat the solution in a suspended system. At
      higher phenol levels (> 1000 mg/L), however, such HFMBR-immobilized cells could
      degrade phenol to a tolerable concentration with weak substrate-inhibition
      effect, and the degradation that followed could be completed by suspended
      cultures due to their larger degradation rate. The process development in an
      HFMBR system was also discussed.

PMID- 15236252
TI  - Gelation conditions and transport properties of hollow calcium alginate capsules.
AB  - The diameter, membrane thickness, and compression intensity of hollow Ca-alginate
      capsules were measured at different gelation conditions, such as the reactant
      concentration, dropping velocity, and gelation time. The optimum operation
      conditions for preparing capsules were determined at 100 g/L CaCl(2), 10 g/L
      sodium alginate (Na-alginate), a dropping velocity of 150 droplets/min, and a
      gelation time of 10 min. Diffusion of some saccharide and amino acid from bulk
      solution into capsules was investigated, and the diffusion coefficients were
      calculated by the developed mathematical model. All the tested substances can
      diffuse easily into the capsules. The combined diffusion coefficients of the
      capsule D(m) are 92-99% as large as their diffusion coefficients in pure water,
      while the diffusion coefficients in the capsule membrane D(1) are 60-95% as large
      as those. By employing polyethylene glycol (PEG) and bovine serum albumin
      (fraction V) (BSA(V)), the molecular weight cut-off of the capsule was
      determined. For linear macromolecules, hollow Ca-alginate capsules have a
      molecular weight cut-off of 4000. No diffusion of BSA(V) into the capsules was
      observed.

PMID- 15236253
TI  - Toward construction of a self-sustained clock-like expression system based on the
      mammalian circadian clock.
AB  - Despite recent advances in circadian biology, detailed understanding of how a
      biological pacemaker system is assembled, maintained, and regulated continues to
      be a significant challenge. We have assembled and characterized a first
      generation, regulatable, self-sustained clock-like expression system based on key
      components of the mammalian circadian clock. The molecular setup of the clock
      like oscillator was reduced to the core set of positive and negative elements
      common to all known circadian pacemakers. Sophisticated tetracycline-responsive
      multi-cistronic expression integrated with forefront lentiviral transduction
      tools enabled autoregulated reporter transgene expression in a human cell line.
      We characterized transgene expression kinetics of an artificial oscillator and
      showed that its expression profiles could be modulated by a serum shock and
      administration of regulating tetracycline antibiotics. Design of a generic
      mammalian clock-like expression system will offer novel opportunities to study
      circadian biology and may provide a unique tool for rhythmic expression of
      desired transgenes fostering advances in biopharmaceutical manufacturing, gene
      therapy, and tissue engineering.

PMID- 15236254
TI  - Membrane-aerated microbioreactor for high-throughput bioprocessing.
AB  - A microbioreactor with a volume of microliters is fabricated out of
      poly(dimethylsiloxane) (PDMS) and glass. Aeration of microbial cultures is
      through a gas-permeable PDMS membrane. Sensors are integrated for on-line
      measurement of optical density (OD), dissolved oxygen (DO), and pH. All three
      parameter measurements are based on optical methods. Optical density is monitored
      via transmittance measurements through the well of the microbioreactor while
      dissolved oxygen and pH are measured using fluorescence lifetime-based sensors
      incorporated into the body of the microbioreactor. Bacterial fermentations
      carried out in the microbioreactor under well-defined conditions are compared to
      results obtained in a 500-mL bench-scale bioreactor. It is shown that the
      behavior of the bacteria in the microbioreactor is similar to that in the larger
      bioreactor. This similarity includes growth kinetics, dissolved oxygen profile
      within the vessel over time, pH profile over time, final number of cells, and
      cell morphology. Results from off-line analysis of the medium to examine organic
      acid production and substrate utilization are presented. By changing the gaseous
      environmental conditions, it is demonstrated that oxygen levels within the
      microbioreactor can be manipulated. Furthermore, it is demonstrated that the
      sensitivity and reproducibility of the microbioreactor system are such that
      statistically significant differences in the time evolution of the OD, DO, and pH
      can be used to distinguish between different physiological states. Finally,
      modeling of the transient oxygen transfer within the microbioreactor based on
      observed and predicted growth kinetics is used to quantitatively characterize
      oxygen depletion in the system.

PMID- 15236255
TI  - Fine-needle aspiration cytology of malignant peripheral nerve sheath tumors.
AB  - The histopathologic features of malignant peripheral nerve sheath tumors (MPNSTs)
      have been well described. There have been limited studies on the cytologic
      features of MPNST. In this present study, we have retrospectively reviewed eight
      histopathology confirmed cases of MPNST over a 5-year period. Detailed
      cytomorphological analysis of these cases was carried out individually by two
      observers. On cytology, these cases were diagnosed as benign spindle-cell tumor
      (two), spindle-cell tumor possibly benign (one), spindle-cell tumor possibly
      malignant (one), malignant spindle-cell tumor (two), spindle-cell tumor, and
      neural origin (two). The cardinal cytomorphologic features were loosely cohesive
      clusters and fascicular arrangement of spindle cells with rounded ends. The
      kinking of nuclei was not a conspicuous finding. Fibrillary background was noted
      in two of the cases. Nuclear pleomorphism was ranged from mild to moderate
      degree. One case exhibited extensive intranuclear pseudoinclusions. Mitotic
      figures (including atypical forms) were present in almost all the cases. Possibly
      a constellation of cytologic features such as clusters of short and long
      fascicles of cells admixed with dissociated spindle cells of round-ended nuclei
      and prominent nucleoli on myxoid or fibrillary background and frequent mitosis
      may be helpful in diagnosis of MPNSTs. The cytomorphologic features along with
      clinical correlation are necessary to increase the diagnostic accuracy of MPNST
      on aspiration cytology.

PMID- 15236256
TI  - Proliferation patterns of cervical cells as visualized in Leiden liquid cytology
      slides.
AB  - The Leiden liquid-based cytology method for the preparation of optimal
      cytological slides is reported. In such slides, the proliferation pattern of
      cervical cells can be visualized in detail. Cervical smears and suspension
      preparations of 665 consecutive unselected patients received in 2003 were
      studied. Of the 665 patients, 26 (10 normal, 10 with cervical atrophy, 5 with
      mild dysplasia, and 1 carcinoma in situ) were selected. After using the Thermo
      Shandon Papspin, the wet slides were placed on a hot plate and dried for 30 min.
      Proliferation of the cervical cells was visualized in brown by staining the cells
      for MiB-1 antigen, and nuclear DNA in blue by a standardized short staining with
      hematoxylin. We found excellent high-resolution demonstrability of cell cycle
      related MiB-1 distribution in the well-flattened nuclei. The phase of the cell
      cycle could be deduced from brown-blue staining patterns. There was a significant
      increase of MiB-1-positive cell yield related to progression in the degree of
      pathology.

PMID- 15236257
TI  - Aspiration cytology of sarcomatoid carcinoma of the breast: Report of a case with
      cystic change.
AB  - Sarcomatoid/metaplastic carcinomas of the breast are rare breast malignancies
      that show a myriad of cytohistologic patterns in aspirates. These poorly
      differentiated invasive carcinomas contain both ductal and mesenchymal elements
      with transitional forms displaying either spindle, squamous, chondroid, or
      osseous differentiation. We describe such a neoplasm in a 68-yr-old woman, the
      diagnosis of which was missed at the initial fine-needle aspiration (FNA) due to
      cystic change. Extensive cystic change in a sarcomatoid carcinoma is unusual and
      is reported for the first time in the English literature.

PMID- 15236258
TI  - Extracellular material in adenoid cystic carcinoma of the salivary glands: a
      comparative cytological study with other salivary myoepithelial tumors.
AB  - The objective of this study was to clarify extracellular materials (ECMs) in
      adenoid cystic carcinoma (AdCC) and compare these to those found in other
      salivary gland tumors with myoepithelial differentiation. The ECM was examined
      with Papanicolaou, May-Grunwald-Giemsa (MGG), and alcian blue stain at pH 2.5.
      The ECM in AdCC was classified into three types according to their staining
      patterns: clear, hyalinized, and membrane type. The incidence of clear-type
      globule material with magenta on MGG was low in other salivary gland tumors with
      myoepithelial differentiation. The ECM was identified in other salivary gland
      tumors with myoepithelial differentiation. However, AdCC has the greatest variety
      of ECM. These findings are useful to understand the character of AdCC and
      differential diagnosis of the other salivary gland tumors with myoepithelial
      differentiation.

PMID- 15236259
TI  - Detection of high-risk human papillomavirus (HPV) DNA by Hybrid Capture II in
      women referred due to atypical glandular cells in the primary screening.
AB  - We assessed the detection of high-risk human papillomavirus DNA (HPV-DNA) in
      women examined by a second Pap smear due to atypical glandular cells (AGC)
      detected in their screening Pap smear. In 91 women included in the study, a
      second Pap smear was taken and HPV-DNA test was performed using Hybrid Capture II
      (HC II). The second Pap smear showed no abnormalities in 28 (31%) cases, ACG in
      17 (19%) cases, and high-grade squamous intraepithelial lesions (HSIL) or worse
      in 24 (26%). HC II test was positive in 36% of the cases. Considering the second
      Pap smear diagnosis, HPV-DNA was detected in 87% of the women with HSIL, 100% of
      women with in situ adenocarcinoma, and only in 11% of the women with no
      abnormalities. The use of the second Pap smear combined with HPV-DNA may improve
      the management of women with AGC in the primary screening.

PMID- 15236260
TI  - Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin
      lymphoma.
AB  - We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive
      non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and
      53 cases had concurrent flow cytometric analysis. FNA (cytology and flow
      cytometry) and core-needle biopsy were evaluated independently. FNA was
      diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and
      small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was
      diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of
      cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core
      needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core
      needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle
      biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient
      samples were reduced to 16% (12/74). There was no clear advantage in the
      diagnosis and classification of small B-cell NHL by adding core-needle biopsy to
      FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA
      in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core
      needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient
      for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach
      reduces the number of insufficient cases and is recommended in routine FNA
      practice.

PMID- 15236261
TI  - Polypoid sinonasal lesion in a diabetic patient.

PMID- 15236262
TI  - Novel tyramide-based tyrosinase assay for the detection of melanoma cells in
      cytological preparations.
AB  - Fine-needle aspiration (FNA) has been used as a fast, minimally invasive, and
      reliable method for the evaluation of enlarged lymph nodes. However, there are
      some cases where the definitive diagnosis cannot be elicited with morphology
      alone, especially cases without a known primary lesion. Although
      immunocytochemical studies may be helpful in some situations, they are often
      complicated by nonspecific staining. Recently, a novel tyramide-based tyrosinase
      assay was developed. Since melanocytes, both benign and malignant, produce
      tyrosinase, we postulated that this assay could be useful as an in situ
      biochemical diagnostic test. We modified the Perkin Elmer TSA assay, a commercial
      assay based on tyramide, a tyrosine analog that is a substrate for tyrosinase,
      for use on air-dried cytological preparations. We validated the assay on cell
      lines, then tested a small series of melanoma and nonmelanoma cytology specimens.
      The YUGEN8 melanoma cell line was used to optimize the assay and it showed
      abundant reaction product, while HeLa cells served as a negative control. All
      melanoma cytology specimens were positive and all nonmelanoma specimens were
      negative. These results suggest that this simple, fast, and inexpensive assay is
      a sensitive and specific method for detection of melanoma cells in cytology
      specimens. This method may be a useful ancillary procedure for the resolution of
      challenging melanoma cases.

PMID- 15236263
TI  - Fine-needle aspiration cytology of endometrioid adenofibroma of the ovary.
AB  - We report the fine-needle aspiration (FNA) cytology findings of endometrioid
      adenofibroma arising in the ovary of a 60-year-old woman who presented with
      vaginal bleeding. Imaging studies revealed a large pelvic mass, which was sampled
      by computed tomography-guided FNA and core biopsy. The FNA yielded cellular
      smears composed of bland endometrioid cells and fragments of ovarian-type stroma.
      The core biopsy showed a biphasic process comprising bland endometrioid glands in
      a spindle-cell stroma. Immunohistochemical studies performed on the core showed
      the stroma to be CD10-negative and smooth muscle actin-positive. Subsequent
      resection of the tumor confirmed the diagnosis and revealed an adenocarcinoma
      arising in the tumor that was not sampled by FNA. To our knowledge, the cytologic
      features of ovarian endometrioid adenofibroma have not been previously described.

PMID- 15236264
TI  - Metastatic bronchioloalveolar carcinoma presenting as a solitary thyroid nodule:
      report of a case with fine-needle aspiration cytopathology.
AB  - Although cancers metastatic to the thyroid are frequently mentioned in autopsy
      studies, such a finding is quite rare in routine clinical practice. Metastatic
      non-small-cell carcinomas to the thyroid may present a diagnostic dilemma,
      particularly when they share morphological similarities with primary thyroid
      tumors. Herein, we report a case of metastatic bronchioloalveolar carcinoma that
      presented as an isolated left thyroid nodule in a 68-year-old woman. The
      aspirates were cellular and showed numerous papillary-like tissue fragments,
      elongated nuclei with prominent nuclear grooves, frequent mitoses, and psammoma
      bodies. The latter features raised the possibility of papillary thyroid
      carcinoma. However, also seen were three-dimensional tumor nests and acinar
      forming fragments. Immunostains (positive for cytokeratin-7 and carcinoembryonic
      antigen and negative for cytokeratin-20 and thyroglobulin) confirmed the
      metastatic nature of the carcinoma. In a patient with known primary neoplasm, the
      differential diagnosis of a thyroid nodule should always include a metastatic
      lesion along with primary neoplasia.

PMID- 15236265
TI  - Histiocytes containing immunoglobulin crystals in the urine of a patient with IgA
      kappa plasmacytoma of the bladder.
AB  - Exfoliative cytology specimens from patients with plasma cell dyscrasias are
      rarely diagnostic, though there are reports of neoplastic plasma cells observed
      in pleural fluid and urine. Immunoglobulin concretions or crystals associated
      with neoplastic plasma cell populations have been well described. These crystals
      may be found within plasma cell nuclei or cytoplasm, extracellularly, or within
      cells of histiocytic lineage where they are presumably derived by phagocytosis.
      To the best of our knowledge, this is the first report of immunoglobulin crystals
      within histiocytes in the urine of a patient with plasmacytoma. A 61-year-old
      male underwent routine cystoscopy and urine collection to evaluate hematuria. The
      bladder biopsy demonstrated IgA kappa-producing plasmacytoma. Urine cytopsin
      preparations did not contain plasma cells, but there were histiocytic cells with
      degenerative nuclei and eccentrically located cytoplasmic spherical refractile
      hyaline crystals thought to be immunoglobulin crystals. This was supported by
      immunocytochemical staining.

PMID- 15236266
TI  - Thyroid low-grade B-cell lymphoma (MALT type) with extreme plasmacytic
      differentiation: report of a case diagnosed by fine-needle aspiration and flow
      cytometric study.
AB  - We describe a case of thyroid marginal-zone B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT lymphoma) with extreme plasmacytic differentiation in an 80
      year-old woman who had presented with a rapidly growing thyroid swelling. The
      diagnosis was initially suspected on fine-needle aspiration (FNA) and
      subsequently confirmed by flow cytometric analysis of the aspirated material. The
      smears revealed features of Hashimoto's thyroiditis admixed with large numbers of
      atypical large plasmacytoid lymphoid cells accompanied by variable numbers of
      small lymphocytes and mature plasma cells. The differential diagnosis of a
      predominantly plasmacytic smears on FNA of the thyroid is discussed herein, with
      emphasis on the role of immunophenotypic studies to exclude or confirm the
      diagnosis of lymphoma.

PMID- 15236267
TI  - Unsuspected systemic amyloidosis diagnosed by fine-needle aspiration of the
      salivary gland: case report.
AB  - Amyloidosis of the head and neck region may represent a local amyloidoma or a
      manifestation of systemic disease. Involvement of major salivary glands by either
      primary or secondary forms of amyloidosis is very rare. We describe a case of
      systemic amyloidosis that initially presented as submandibular gland mass and was
      diagnosed by fine-needle aspiration (FNA). A 69-year-old male presented with
      submandibular mass. His past medical history was significant for left forearm
      melanoma that was excised 6 years ago and tricuspid valve endocarditis after
      valvular replacement 3 months prior to FNA of the submandibular gland. The
      patient had no symptoms or clinical and laboratory data suggestive of
      amyloidosis. FNA specimen showed salivary gland tissue and abundant amorphous
      material, which stained positive for amyloid with Congo red stain and showed
      typical birefringence when examined by polarized microscopy. Further workup of
      the patient revealed generalized amyloidosis with multiorgan involvement by the
      disease. This case demonstrates that FNA can be a useful technique in the
      diagnosis of unsuspected amyloidosis.

PMID- 15236268
TI  - Atypical teratoid/rhabdoid tumor: cytology and differential diagnosis in adults.
AB  - Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant intracranial neoplasms
      that usually occur in the posterior fossa of children. They are characterized by
      cells with paranuclear rhabdoid inclusions, a mesenchymal and epithelial
      immunohistochemical profile, and 22q deletions with inactivation of the
      INI1/hSNF5 gene. Although they usually occur in young children, AT/RTs are being
      recognized in adults with increasing frequency. We report the cytologic features
      of an AT/RT from the cerebellum of a 45-year-old man and discuss the differential
      diagnosis in adults.

PMID- 15236270
TI  - Corpora amylacea in cervicovaginal smears.

PMID- 15236269
TI  - Can cytomorphology differentiate between benign nodules and tumors arising in
      Graves' disease?
AB  - Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves'
      disease (GD) can pose diagnostic difficulties because the cytomorphologic changes
      in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In
      addition, treatment of GD patients with radioactive iodine (RAI) may cause
      significant cytologic atypia, further increasing the diagnostic difficulty. From
      March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients
      with GD underwent FNA; 3 patients had received RAI treatment. Three cases were
      diagnosed as suspicious for PTC and 11 as benign. Three patients with the
      diagnosis of suspicious for PTC on FNA underwent surgery and were found to have
      papillary carcinoma. We assessed all cases to find key cytologic features that
      can differentiate between nodules with reactive/reparative nuclear atypia from
      PTC arising in GD. The cytologic features assessed included cellularity, amount
      of colloid, monotony of the cell population, oncocytic features, cell crowding,
      lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery
      chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each
      feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0
      representing absence and 4 representing a predominance of the feature. The mean
      value of each feature was calculated and the benign and malignant lesions were
      compared using the unpaired t-test. Four features were found to be statistically
      significant in the diagnosis of PTC as compared to the benign nodules in GD. The
      nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin,
      intranuclear grooves, and small eccentric nucleoli. All other features studied
      were not found to be statistically significant. There does exist an overlap
      between the cytologic features of benign nodules and PTC arising in GD. However,
      adherence to strict diagnostic criteria (nuclear elongation, pale powdery
      chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the
      diagnosis of PTC arising in GD.

PMID- 15236271
TI  - Challenge of curing cancer worldwide--two ends of the spectrum.

PMID- 15236272
TI  - The pediatric research equity act and oncology.

PMID- 15236273
TI  - Statement by members of the Ponte di Legno Group on the right of children to have
      full access to essential treatment for acute lymphoblastic leukemia.

PMID- 15236274
TI  - A comparison of red blood cell thiopurine metabolites in children with acute
      lymphoblastic leukemia who received oral mercaptopurine twice daily or once
      daily: a Pediatric Oncology Group study (now The Children's Oncology Group).
AB  - INTRODUCTION: Mercaptopurine is an important antimetabolite for treatment of
      childhood acute lymphoblastic leukemia (ALL). It has been prescribed to be given
      daily without therapeutic monitoring of drug levels. After first-pass metabolism
      by hepatic xanthine oxidase (XO), mercaptopurine is converted into two major
      intracellular metabolites, thioguanine nucleotide (TGN) and methylated
      mercaptopurine metabolites (including methylated thioinosine nucleotides), which
      are cytotoxic in vitro. Its short plasma half-life and S-phase-dependent
      pharmacokinetics suggest that biologically active concentration and exposure
      duration may be critical to cell kill. METHODS: Pediatric Oncology Group (POG)
      9605, a randomized, open label phase III study of standard-risk ALL, was designed
      to compare daily with twice-daily mercaptopurine during continuation therapy. Red
      blood cell (RBC) TGN and methylated mercaptopurine metabolite levels were
      measured as surrogates of leukemic cell levels in a randomly selected subset of
      patients. TGN and methylated mercaptopurine metabolites were analyzed
      quantitatively by high-performance liquid chromatography (HPLC) and reported in
      ng/8 x 10.8 RBC. Statistical inferences utilized multiple linear regression.
      RESULTS: One hundred eighteen patients received mercaptopurine 75 mg/m(2) daily
      and 108 received 37.5 mg/m(2)/dose twice daily. Descriptive statistics for the
      daily group showed the median TGN was 42 ng (mean and standard deviation [SD] =
      48 +/- 35, quartiles 29-64). For the twice daily group, it was 40 ng (mean and SD
      = 40 +/- 27, quartiles 26-53). For methylated mercaptopurine metabolites, the
      daily group median was 2,020 ng (mean and SD = 2,278 +/- 1,559, quartiles 1,247
      3,162); the twice daily group median was 1,275 ng (mean and SD = 1,580 +/- 1,240,
      quartiles 599-2,369). When adjusted for the covariables: actual dosage, days on
      study, age at diagnosis, white blood cell count, gender, Black race compared with
      not, and Hispanic compared with not, daily dosing resulted in significantly
      higher average methylated mercaptopurine metabolites by 668 (standard error [SE]
      = 179, P = 0.001) and a trend toward higher average TGNs by 6.2 (SE = 4.2, P =
      0.14). CONCLUSIONS: Daily dosing of mercaptopurine resulted in higher mean red
      cell methylated mercaptopurine metabolites when compared to split (twice a day
      dosing). The data were inconclusive with respect to TGNs. The relationships of
      methylated mercaptopurine metabolites and TGNs to clinical outcomes will be
      elucidated as part of the maturing 9605 data.

PMID- 15236275
TI  - Cerebrospinal fluid insulin-like growth factor (IGF-1) and insulin-like growth
      factor binding protein (IGFBP-2) in children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) has specific effects on axonal
      growth and myelination, low CSF IGF-1 levels being found in some severe
      neurologic diseases. We studied the levels of CSF IGF-1 and IGF binding protein-2
      (IGFBP-2) in children with ALL to find out whether these levels correlated with
      any of the neurological deficits observed. METHODS: IGF-1 and IGFBP-2 levels were
      prospectively measured by radioimmunoassay in the CSF of 14 children with ALL
      throughout the ALL chemotherapy. These were compared with the levels of 16
      control subjects and of patient groups with severe neurological diseases.
      RESULTS: During induction, the children with ALL had subnormal CSF IGF-1 levels
      which improved after 2 months. In seven individuals, two with severe vincristine
      polyneuropathy, the subnormal levels persisted throughout the chemotherapy.
      CONCLUSIONS: Our findings suggest impairment of the IGF-1 trophic system during
      induction by a mechanism so far unknown. Correlation with disturbed neuronal
      function could not be statistically proven.

PMID- 15236276
TI  - p53 protein expression does not correlate with EBV status in childhood B non
      Hodgkin lymphomas.
AB  - BACKGROUND: The p53 tumor suppressor gene is affected in a wide range of human
      cancers, including hematological malignancies. This gene encodes a nuclear
      phosphoprotein p53, which plays a key role in cell cycle arrest, induction of
      apoptosis, and DNA repair. Mutations of the p53 gene often lead to the
      accumulation of the mutated protein in the nucleus of neoplastic cells. However,
      p53 protein expression is frequently detected in non-Hodgkin lymphomas (NHL)
      without any correlation with p53 mutations. This discordance suggests the
      existence of other mechanisms to stabilize the p53 protein, including binding of
      p53 protein to viral proteins. p53 protein has been shown to bind to proteins
      encoded by the Epstein-Barr virus (EBV). PROCEDURE: The aim of this study was to
      analyze p53 expression in childhood B-NHL and correlate its expression in the
      absence of p53 mutations with EBV in order to investigate a possible involvement
      of EBV in p53 stabilization. DESIGNS AND METHODS: Tumor specimens from 35
      children with B-NHL were analyzed by immunohistochemistry (IHC) with the DO7
      monoclonal antibody, which recognizes an epitope at N-terminus of p53 protein and
      reacts with wild type and mutant proteins. To detect p53 mutations, PCR/SSCP and
      sequencing were performed. EBV status was determinated using a specific PCR
      technique. RESULTS: The overall frequency of p53 immunostaining positivity was
      45% (16 of 35). p53 mutations were detected in nine patients (25.6%). p53
      immunoreactivity was observed in all cases with mutations. Additionally, we
      identified 7 p53 positive cases among 26 tumors without mutations. EBV DNA was
      detected in 24 of 35 cases. Four patients with p53 expression dissociated from
      mutation were EBV positive. No statistically significant association was found
      between p53 expression and EBV cases despite the exclusion of those patients in
      which p53 expression was related with p53 mutations (P = 0.28 and 0.54,
      respectively). CONCLUSIONS: Our results suggested that in childhood B-NHL, the
      expression of p53 dissociated from mutations could not be related to EBV
      infection. Further studies with larger patient sets will be necessary to
      determinate if EBV-encoded protein may play a role for nuclear accumulation of
      p53 protein.

PMID- 15236277
TI  - 4S neuroblastoma: the long-term outcome.
AB  - BACKGROUND: Stage 4S neuroblastoma is associated with a high rate of spontaneous
      maturation and involution, with survival rates of 70-90%. There is little long
      term follow-up data describing the disease status or late effects. The aim of
      this study was to assess the clinical outcome and imaging findings in long-term
      survivors of 4S neuroblastoma. METHODS: The patient population was identified
      from a single centre over 26 years. Twenty-five of 31 consecutive patients were
      long-term survivors. Five died from disease progression and one from cerebral
      palsy related complications. All survivors underwent clinical examination.
      Abdominal ultrasound scanning, liver function tests, hepatitis viral screen, and
      urinary catecholamines were performed. RESULTS: The mean age at diagnosis was 8
      +/- 9 weeks with a mean age when studied of 11 years and 10 months +/- 8 years.
      Twenty of 25 had no significant clinical findings, three had disease associated
      clinical abnormalities (neurological, multiple subcutaneous nodules). Three
      patients had treatment related effects (small testes, urethral stricture,
      radiation induced soft tissue hypoplasia, post-surgical Horners syndrome).
      Persistant adrenal enlargement and calcification was noted in three patients.
      Twelve patients had abnormal liver ultrasound findings ranging from mildly coarse
      echotexture to structural changes without evidence of hepatic dysfunction or
      infection. Treatment did not correlate with abnormal hepatic ultrasound findings.
      CONCLUSIONS: The majority of long-term survivors of stage 4S neuroblastoma have
      no clinically or radiologically significant sequelae but do have residual
      abnormalities. These findings have implications for subsequent management of
      unrelated medical conditions in this patient group.

PMID- 15236278
TI  - Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy
      for intracranial germinomas: failure of a primary chemotherapy approach.
AB  - PURPOSE: High rates of overall and event-free survival have been reported in
      patients with intracranial germinomas treated with craniospinal radiotherapy.
      More recently, similar results have been reported with chemotherapy combined with
      radiotherapy to more localized treatment volumes. Our interest in exploring
      chemotherapy without radiotherapy in patients with CNS germinomas was based on
      concerns about the late sequelae of radiotherapy to the brain or neuraxis and
      also the well documented success of chemotherapy alone in patients with
      disseminated extracranial germinomas. The primary objective of this study was to
      determine whether intensive cisplatin and cyclophosphamide-based combination
      chemotherapy, without radiotherapy, was effective in patients with CNS
      germinomas. PATIENTS AND METHODS: Nineteen patients were enrolled, ranging in age
      from 1 to 24 years (median, 14 years). Thirteen were male. Nine had diabetes
      insipidus. Therapy comprised two courses of Regimen 'A' (cisplatin, etoposide,
      cyclophosphamide, and bleomycin) followed by MRI evaluation. Patients achieving a
      complete remission (CR) completed all planned therapy with two courses of regimen
      'B' (carboplatin, etoposide, and bleomycin). Patients achieving less than a CR
      received two courses of Regimen 'B' followed by another evaluation. Those in CR
      after four courses of treatment received one additional course of Regimen 'A' and
      Regimen 'B', while those not in CR after four treatment courses underwent second
      look surgery and/or radiation therapy. RESULTS: Eleven of 11 patients with
      residual postoperative disease assessable for response achieved a CR. With a
      median follow-up of 6.5 years, eight out of 19 (0.42) patients remain in CR 1
      without radiotherapy and another three patients are in stable second or
      subsequent remissions. Three patients died from treatment-related toxicity and
      another died in CR 1 from an uncharacterized leukoencephalopathy. The 5-year
      event-free survival (EFS) was 0.47 +/- 0.23 and 5-year overall survival (OS) was
      0.68 +/- 0.22. CONCLUSIONS: Intensive cisplatin and cyclophosphamide-based
      chemotherapy was effective in achieving remissions, however, the long-term
      outcome using this treatment program was unsatisfactory and associated with
      unacceptable morbidity and mortality, particularly in patients with diabetes
      insipidus.

PMID- 15236279
TI  - Episcleral plaque brachytherapy for retinoblastoma.
AB  - BACKGROUND: The purpose of this study was to report our experience using
      episcleral plaque brachytherapy (EPBRT) to treat retinoblastoma and to
      demonstrate its applicability in multimodality treatment. PROCEDURE: We treated
      26 tumors in 25 eyes from a group of 21 children with unilateral (n = 4) or
      bilateral (n = 17) retinoblastoma. The group comprised 8 girls and 13 boys; the
      median age was 25 months (range: 2-64 months) at the time of EPBRT. Iodine-125
      ((125)I) was used for all applications. The median dose was 44 Gy (range: 35-47.6
      Gy). EPBRT was administered primarily at the time of relapse after primary
      chemotherapy or radiation therapy. RESULTS: For eyes treated with EPBRT, the eye
      preservation rate was 15/25 with a median follow-up of 47 months (range: 2-198
      months); the lesion control rate was 25/26 with a median follow-up of 13 months
      (range: 1-140 months). The median time to additional whole-eye treatment after
      EPBRT was 12 months (range: 2-105 months). CONCLUSIONS: Similar to previously
      reported series, EPBRT shows a high rate of successful tumor control as a primary
      treatment for retinoblastoma, as well as a secondary therapy at the time of
      relapse. EPBRT also allows for a clinically significant delay in the time to
      additional measures for the affected eye. Therefore, EPBRT should be considered
      as a form of local ophthalmic therapy that avoids or delays the use of external
      beam radiotherapy, especially for patients primarily treated with chemotherapy
      who might require consolidation therapy.

PMID- 15236280
TI  - A survey of clinical productivity and current procedural terminology (CPT) coding
      patterns of pediatric hematologist/oncologists.
AB  - BACKGROUND: Subspecialty-specific normative values for clinical productivity of
      practicing pediatric hematologist/oncologists have not been well established.
      This information could be a useful adjunct in administrative decision-making in
      areas such as necessary levels of physician staffing and development of
      compensation plans. METHODS: Current procedural terminology (CPT) coding
      information was obtained from 27 pediatric hematology/oncology groups. Clinical
      productivity was assessed by overall number of patient encounters and the total
      number of physician work relative value units (RVU) as defined by the resource
      based relative value scale. The average physician productivity within each
      individual program was calculated. To determine uniformity of CPT coding, an
      additional survey solicited mock patient encounter documentation and CPT coding
      for a simple clinical vignette. RESULTS: A broad range of clinical productivity
      was observed for both numbers of patient encounters and RVU. Evaluation of the
      CPT coding data of the surveyed groups revealed differences in usage of certain
      evaluation and management (E/M) codes and procedural and specimen interpretation
      codes. Within individual categories of E/M service codes, a wide variation in
      assigned CPT code levels was also observed. This observation was supported by
      differences in the E/M coding for the clinical vignette. CONCLUSIONS: Assessment
      and tracking of physician productivity can provide useful information for the
      administrative management of pediatric hematology/oncology programs. Caution must
      be exercised, however, when making productivity comparisons with other
      subspecialties or even between pediatric hematology/oncology programs. Such
      comparisons should take into account the number of patient encounters,
      characteristics of E/M coding patterns, the use of physician extenders, as well
      as overall RVU production.

PMID- 15236281
TI  - Successful treatment of progressive stage 4s hepatic neuroblastoma in a neonate
      with intra-arterial chemoembolization.
AB  - Stage 4s neuroblastoma (NB) is a unique entity seen in infants less than 1 year
      of age, with metastatic disease confined to liver, skin, or bone marrow. Despite
      metastatic spread, stage 4s NB has a favorable outcome. An exception to this is
      seen in neonates who present with progressive enlargement of the liver with
      secondary respiratory compromise and liver failure. We describe a 4-week-old
      neonate who presented with 4s NB, with a rapidly enlarging liver, resulting in
      respiratory and hepatic failure, who had a rapid, sustained, and ongoing response
      to chemoembolization of the hepatic artery. This approach is feasible at this
      age, and may be effective in improving the outcome in this group of patients.

PMID- 15236282
TI  - Pegylated liposomal doxorubicin hydrochloride (PLD) for advanced sarcomas in
      children: preliminary results.

PMID- 15236283
TI  - Concurrent cystic mediastinal lymphangioma and paratesticular rhabdomyosarcoma.
AB  - The current report describes a 23-month-old boy with paratesticular
      rhabdomyosarcoma who was incidentally diagnosed as also having an isolated
      mediastinal cystic lymphangioma. The association of childhood rhabdomyosarcoma
      with various congenital anomalies and genetic alterations such as p53 mutations
      have been well known. However, mediastinal cystic lymphangioma has not been
      reported among the congenital anomalies diagnosed in rhabdomyosarcoma. Both
      rhabdomyosarcoma and lymphangioma originate from mesenchymal cells. This
      association may be coincidental or may point to a common genetic and/or
      developmental disorder of the mesencymal tissue.

PMID- 15236284
TI  - Infective endocarditis (IE) in children receiving treatment for cancer.
AB  - Infective endocarditis (IE) is rare in children but is associated with
      substantial morbidity/mortality. Medical records of 161 new patients admitted to
      the Pediatric Oncology Unit in a 2 years period were reviewed to identify
      patients with a diagnosis of IE following the Duke criteria. Nine patients
      developed IE; their ages ranged from 2.4 to 11.3 years. The patients received
      treatment according to the results of blood cultures. TIPs are associated with a
      high rate of IE. The diagnosis of IE should be considered in children with cancer
      who have major/minor criteria as defined by the Duke criteria.

PMID- 15236285
TI  - Autoimmune lymphoproliferative syndrome: a cause of chronic splenomegaly,
      lymphadenopathy, and cytopenias in children-report on diagnosis and management of
      five patients.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) usually manifests in early
      childhood with splenomegaly, lymphadenopathy, and cytopenias. In most patients,
      it results from mutations in genes that regulate lymphocyte apoptosis via the Fas
      pathway. Here, we report five children with ALPS. All five children had
      splenomegaly, cytopenias, and hypertriglyceridemia at presentation; four had
      lymphadenopathy. Mutations in the Fas receptor gene were demonstrated in three
      children. Clinical picture is variable: in only one child manifestations are
      severe enough to require immunosuppressive therapy. Diagnosis of ALPS can be
      challenging and increased awareness of the disease can result in more directed
      diagnostic approaches as well as earlier initiation of treatment.

PMID- 15236286
TI  - Management of coagulopathy with recombinant factor VIIa in a neonate with
      echovirus type 7.
AB  - A 5-day-old newborn presented with neonatal enteroviral infection. The patient's
      hospital course was complicated by acute liver dysfunction, renal insufficiency,
      fluid overload, respiratory failure, hypertension, catheter related thrombosis,
      Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and
      disseminated intravascular coagulation (DIC). Administration of fresh frozen
      plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and
      led to significant fluid overload. Recombinant activated factor VII (rFVIIa,
      Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus
      (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5
      16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until
      the patient's liver function recovered. The patient's blood product requirement
      significantly decreased and his fluid overload resolved. Administration of rFVIIa
      appears to have stabilized the coagulation process. The patient appears to have
      fully recovered from the infection's complications.

PMID- 15236287
TI  - Endobronchial non-Hodgkin lymphoma in an adolescent.

PMID- 15236288
TI  - Successful therapy of choroid plexus carcinoma.

PMID- 15236289
TI  - Favorable outcome for children with paratesticular alveolar history
      rhabdomysosarcoma.

PMID- 15236290
TI  - Valproic acid treatment of glioblastoma multiforme in a child.

PMID- 15236291
TI  - Bone mineral density in childhood acute lymphoblastic leukemia (ALL) during and
      after treatment.

PMID- 15236293
TI  - Use of PEG-interferon alfa-2a plus ribavirin as treatment for chronic HCV
      hepatitis in a child cured of ALL.

PMID- 15236294
TI  - Megatherapy in the treatment of high-risk relapsed Wilms tumor.

PMID- 15236295
TI  - Internal energy build-up in matrix-assisted laser desorption/ionization.
AB  - This paper reports detailed studies on the internal energy of ions formed in
      matrix-assisted laser desorption/ionization (MALDI) using delayed extraction
      MALDI-time-of-flight (TOF) and atmospheric pressure (AP) MALDI mass spectrometric
      (MS) methods. We use benzylpyridinium cations as internal energy probes. Our
      study reveals three distinct contributions to internal energy build-up in vacuum
      MALDI (classical MALDI-TOF), each having different effects on ion fragmentation.
      Some fragments are formed before ion extraction (i.e. no more than 100 ns after
      the laser impact), and they are therefore well resolved and recorded as sharp
      signals in the MALDI-TOFMS scan. This prompt fragmentation can have two origins:
      (i) in-plume thermal activation, presumably always present, and (ii) in-plume
      chemical activation, in the course of reactions with hydrogen radicals. In
      addition to early internal energy build-up associated with these well-resolved
      promptly formed fragments, a broad peak slightly offset to higher masses could be
      detected corresponding to fragments formed after the extraction has started. This
      second signal corresponds to a third source of internal energy in MALDI ions,
      (iii) the extraction-induced collisional activation of the ions with the neutral
      components of the plume. These three contributions are difficult to quantify in
      vacuum-MALDI, because of the combined influence of several parameters (nature of
      the matrix, spot-to-spot variability, total laser exposure, delay time,
      acceleration voltage) on extraction-induced fragmentation. AP-MALDI, on the other
      hand, has two advantages for comparative studies of analyte fragmentation. First,
      extraction-induced fragmentation is absent, and only the contributions of early
      plume activation remain. Second, the reproducibility is far better than in vacuum
      MALDI. AP-MALDI is therefore expected to shed new light on the early steps of the
      MALDI process.

PMID- 15236296
TI  - Characterization of non-covalent complexes of rutin with cyclodextrins by
      electrospray ionization tandem mass spectrometry.
AB  - Electrospray ionization tandem mass spectrometry (ESI-MS(n)) and the phase
      solubility method were used to characterize the gas-phase and solution-phase non
      covalent complexes between rutin (R) and alpha-, beta- and gamma-cyclodextrins
      (CDs). The direct correlation between mass spectrometric results and solution
      phase behavior is thus revealed. The order of the 1 : 1 association constants
      (K(c)) of the complexes between R and the three CDs in solution calculated from
      solubility diagrams is in good agreement with the order of their relative peak
      intensities and relative collision-induced dissociation (CID) energies of the
      complexes under the same ESI-MS(n) condition in both the positive and negative
      ion modes. Not only the binding stoichiometry but also the relative stabilities
      and even binding sites of the CD-R complexes can be elucidated by ESI-MS(n). The
      diagnostic fragmentation of CD-R complexes, with a significant contribution of
      covalent fragmentation of rutin leaving the quercetin (Q) moiety attached to the
      CDs, provides convincing evidence for the formation of inclusion complexes
      between R and CDs. The diagnostic fragment ions can be partly confirmed by the
      complexes between Q and CDs. The gas-phase stability order of the deprotonated CD
      R complexes is beta-CD-R > alpha-CD-R > gamma-CD/R; beta-CD seems to bind R more
      strongly than the other CDs.

PMID- 15236297
TI  - Distinguishing N-oxide and hydroxyl compounds: impact of heated capillary/heated
      ion transfer tube in inducing atmospheric pressure ionization source
      decompositions.
AB  - In the pharmaceutical industry, a higher attrition rate during the drug discovery
      process means a lower drug failure rate in the later stages. This translates into
      shorter drug development time and reduced cost for bringing a drug to market.
      Over the past few years, analytical strategies based on liquid
      chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes
      and presently accommodate most of the needs of the pharmaceutical industry. Among
      these LC/MS techniques, collision induced dissociation (CID) or tandem mass
      spectrometry (MS/MS and MS(n)) techniques have been widely used to identify
      unknown compounds and characterize metabolites. MS/MS methods are generally
      ineffective for distinguishing isomeric compounds such as metabolites involving
      oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure
      ionization (API) source decomposition methods have been shown to aid in the mass
      spectral distinction of isomeric oxygenated (N-oxide vs hydroxyl)
      products/metabolites. In previous studies, experiments were conducted using mass
      spectrometers equipped with a heated capillary interface between the mass
      analyzer and the ionization source. In the present study, we investigated the
      impact of the length of a heated capillary or heated ion transfer tube (a newer
      version of the heated capillary designed for accommodating orthogonal API source
      design) in inducing for-API source deoxygenation that allows the distinction of N
      oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline-N-oxide (Q
      NO) and 8-hydroxyquinoline-N-oxide (HO-Q-NO) were used as model compounds on
      three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum).
      Irrespective of heated capillary or ion transfer tube length, N-oxides from this
      class of compounds underwent predominantly deoxygenation decomposition under
      atmospheric pressure chemical ionization conditions and the abundance of the
      diagnostic [M + H - O](+) ions increased with increasing vaporizer temperature.
      Furthermore, the results suggest that in API source decompostion methods
      described in this paper can be conducted using mass spectrometers with non-heated
      capillary or ion transfer tube API interfaces. Because N-oxides can undergo in
      source decomposition and interfere with quantitation experiments, particular
      attention should be paid when developing API based bioanalytical methods.

PMID- 15236298
TI  - Mass spectrometry and partial least-squares regression: a tool for identification
      of wheat variety and end-use quality.
AB  - Rapid methods for the identification of wheat varieties and their end-use quality
      have been developed. The methods combine the analysis of wheat protein extracts
      by mass spectrometry with partial least-squares regression in order to predict
      the variety or end-use quality of unknown wheat samples. The whole process takes
      approximately 30 min. Extracts of alcohol-soluble storage proteins (gliadins)
      from wheat were analysed by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry. Partial least-squares regression was subsequently
      applied using these mass spectra for making models that could predict the wheat
      variety or end-use quality. Previously, an artificial neural network was used to
      identify wheat varieties based on their protein mass spectra profiles. The
      present study showed that partial least-squares regression is at least as useful
      as neural networks for this identification. Furthermore, it was demonstrated that
      partial least-squares regression could be used to predict wheat end-use quality,
      which has not been possible using neural networks.

PMID- 15236299
TI  - Structure, reactivity and thermochemical properties of protonated lactic acid.
AB  - The protonation energetics of lactic acid (LA) were experimentally determined by
      the kinetic method including the entropy effect. The values (proton affinity,
      PA(LA) = 817.4 +/- 4.3 kJ mol(-1); protonation entropy, DeltaS degrees (p)(LA) = 
      2 +/- 5 J K(-1) mol(-1); gas-phase basicity, GB(LA) = 784.5 +/- 4.5 kJ mol(-1))
      agree satisfactorily with computed G2(MP2) expectations (PA(LA) = 811.8 kJ mol(
      1); DeltaS degrees (p)(LA) = -7.1 J K(-1) mol(-1); GB(LA) = 777.4 kJ mol(-1)).
      The fragmentation behaviour of protonated lactic acid (LAH(+)) is dominated by
      carbon monoxide loss followed by elimination of a water molecule. Direct
      dehydration of LAH(+) is only a high-energy process hardly competitive with the
      CO loss. A complete mechanistic scheme, based on MP2/6-31G* calculations, is
      proposed; it involves isomerization of the various protonated forms of LA and the
      passage through the ion-neutral complex between the 2-hydroxypropyl acylium
      cation and a water molecule.

PMID- 15236300
TI  - Structural analysis of 2,6-[bis(alkyloxy)methyl]-phenyltin derivatives using
      electrospray ionization mass spectrometry.
AB  - Electrospray ionization (ESI) mass spectrometry was applied to the structural
      analysis of 23 2,6-[bis(alkyloxy)methyl]phenyltin(IV) derivatives. The mass
      spectra were measured in both polarity modes and multistage tandem mass
      spectrometric (MS(n)) measurements were performed on the ion trap analyser for
      positively charged tin-containing ions. The sum of complementary ions observed in
      the positive-ion mode (i.e. [M-R(3)](+) ion) and in the negative-ion mode (i.e.
      [R(3)](-) ion) permits molecular mass determination in spite of the fact that the
      molecular adducts were often missing even in the first-order mass spectra. The
      subsequent fragmentation of [M-R(3)](+) ions studied by MS(n) and the correlation
      of observed fragment ions with the expected structures of synthesized
      organotin(IV) compounds allowed us to understand the fragmentation behaviour and
      the mechanism of the ion formation for studied compounds. The typical neutral
      losses are alkenes, alcohols and aldehydes. The fragmentation pattern of one
      selected compound was supported by MS(n) measurements of an isotopically labelled
      analogue to confirm unusual ion-molecule reactions of some fragment ions with
      water in the ion trap.

PMID- 15236301
TI  - Synthesis of multi-unit protein hetero-complexes in the gas phase via ion-ion
      chemistry.
AB  - The synthesis of protein hetero-complex ions via ion-ion reactions in the gas
      phase is demonstrated in a quadrupole ion trap. Bovine cytochrome c cations and
      bovine ubiquitin anions are used as reactant species in the stepwise construction
      of complexes containing as many as six protein sub-units. For any set of
      reactants, a series of competitive and consecutive reactions is possible. The
      yield of complex ions for any given sequence of reactions is primarily limited by
      the presence of competitive reactions. Proton transfer represents the most
      important competitive reaction that adversely affects protein complex synthesis.
      In the present data, proton transfer takes place most extensively in the first
      step of complex synthesis, when single protein sub-units are subjected to
      reaction with one another. Proton transfer is found to be less extensive when one
      of the reactants is a protein complex. The generation of hexameric hetero
      complexes containing two cytochrome c molecules and four ubiquitin molecules is
      demonstrated with two different synthesis approaches. The first involved the
      initial reaction of several charge states of cytochrome c and several charges
      states of ubiquitin. The sequence of reactions in this example illustrates the
      array of possible competitive and consecutive reactions associated with even a
      relatively simple set of multiply charged reactants. The second approach involved
      the initial reaction of the 9(+) charge state of cytochrome c and the 5(-) charge
      state of ubiquitin. The latter approach highlights the utility of the multi-stage
      mass spectrometric (MS(n)) capabilities of the ion trap in defining reactant ion
      identities (i.e. charge states and polarities) so that synthesis reactions can be
      directed along a particular set of pathways.

PMID- 15236302
TI  - Screening for dihydropyridine calcium channel blockers in plasma by automated
      solid-phase extraction and liquid chromatography/tandem mass spectrometry.
AB  - A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) screening method
      was developed for the screening of 11 calcium channel blockers of the 1,4
      dihydropyridine type in plasma samples for forensic and clinical cases. Plasma
      samples were extracted by automated solid-phase extraction. Analysis was
      performed using a reversed-phase C(18) column, gradient elution and a triple
      quadrupole mass spectrometer with TurboIonSpray source in positive mode and
      multiple reaction monitoring. This method was found to be selective and sensitive
      for the detection of the target compounds at their therapeutic plasma
      concentrations.

PMID- 15236303
TI  - Site of alkylation of N-methyl- and N-ethylaniline in the gas phase: a tandem
      mass spectrometric study.
AB  - N-Methylaniline (NMA) was ethylated and N-ethylaniline (NEA) was methylated under
      chemical ionization conditions using C(2)H(5)I and CH(3)I, respectively, as
      reagent gases. The structures of the resulting m/z 136 adduct ions have been
      probed using metastable ion and collision-induced dissociation (CID) methods.
      From the similarity of the spectra obtained and from the presence of structure
      diagnostic ions at m/z 59 (CH(3)NHC(2)H(5) (+*)) and m/z 44 (CH(3)NHCH(2) (+)),
      it is concluded that predominantly N-alkylation occurs in both systems. This
      interpretation was aided by the use of C(2)D(5)I and CD(3)I as reagents. Adduct
      ions of m/z 136 were also formed by ethylation of the isomeric toluidines and by
      methylation of the ring-ethylanilines. The resulting CID mass spectra were
      distinctly different from those obtained for the m/z 136 ions obtained by
      alkylation of NMA and NEA. Protonation of N-ethyl-N-methylaniline using
      CH(3)C(==O)CH(3) as Bronsted acid reagent produced an m/z 136 species whose CID
      mass spectrum also featured intense ion signals at m/z 59 and 44. This
      observation led to the conclusion that protonation with acetone as reagent
      results, in this case, in dominant N-protonation. However, the CID mass spectrum
      of the m/z 136 ion formed when CH(3)OH was the protonating agent featured a weak
      signal at m/z 44 and no signal at m/z 59. Hence it was concluded that the latter
      m/z 136 ion contains a larger contribution from the ring-protonated adduct.

PMID- 15236304
TI  - Profiling of sulfoconjugates in urine by using precursor ion and neutral loss
      scans in tandem mass spectrometry. Application to the investigation of heavy
      metal toxicity in rats.
AB  - This paper reports a liquid chromatographic/electrospray ionization mass
      spectrometric (LC/ESI-MS) method for profiling a wide range of structurally
      different sulfoconjugated compounds in urine and its application to the
      characterization of biomarkers for heavy metal toxicity in rat urine.
      Sulfoconjugates were first isolated by solid-phase extraction and the LC
      separation was performed on a reversed-phase column. Sulfoconjugates were
      detected in a triple-quadrupole mass spectrometer by simultaneously monitoring
      constant losses of 80 u (or 80 Th for doubly charged ions), precursors of m/z 80
      (SO(3) (-*)) and precursors of m/z 97 (HSO4-). The ESI-MS detection conditions
      were optimized on dehydroepiandrosterone sulfate and estradiol sulfate and tested
      on other sulfoconjugates. The analysis of urine samples from humans and rats by
      using the developed method allowed the detection of about 15 peaks in each mode
      of detection. It was then applied to the investigation of heavy metal toxicity in
      rats. Comparative analysis of the chromatographic fingerprints of urine from
      control and uranium- and cadmium-treated rats showed several variations in the
      chromatographic pattern of the sulfoconjugates. Diagnostic m/z ratios were
      confirmed by analyzing individual urine samples and one of the observed
      variations seemed to be specific to uranium toxicity. The ion responsible for
      this variation has been identified as 4-ethylphenol sulfate by comparison of its
      chromatographic retention time and collision-induced dissociation mass spectra
      (MS(2) and MS(3) performed on a quadrupole ion trap instrument) with those of the
      synthesized compound.

PMID- 15236305
TI  - Gas-phase ion chemistry of the allene-phosphine and silane-allene-phosphine
      systems.
AB  - The gas-phase ion chemistry of allene-phosphine and silane-allene-phosphine
      mixtures was studied by ion trap mass spectrometry. Rate constants of the main
      processes were measured and compared with the collisional rate constants to
      determine the reaction efficiencies. For the binary mixture, the highest yield of
      C- and P-containing ions is obtained with a 1 : 1 partial pressure ratio among
      the reagents. In the ternary mixture, formation of ion species containing Si, C
      and P together is mainly achieved in reactions of Si/P ions with allene, with a
      lower contribution from reactions of Si/C and C/P ions with phosphine and silane,
      respectively. The formation of ternary ion clusters is related to their possible
      role as precursors of amorphous silicon carbides doped with phosphorus, obtained
      by deposition from properly activated silane-allene-phosphine mixtures.

PMID- 15236306
TI  - Characterization of rat liver microsomal metabolites of AM-630, a potent
      cannabinoid receptor antagonist, by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - The in vitro metabolism of AM-630 was studied by high-performance liquid
      chromatography coupled with tandem mass spectrometry. AM-630 is an
      aminoalkylindole analogue that behaves primarily as a potent CB2-selective
      antagonist. In this study, 17 metabolic products were identified that resulted
      from the incubation of AM-630 in rat liver microsome preparations. Six metabolic
      pathways were proposed to account for all detected metabolites: (1) o
      demethylation of the methoxyphenyl group, (2) morpholinyl ring opening, (3)
      hydroxylation on the methoxy/hydroxyl phenyl ring, (4) hydroxylation on the
      indole ring, (5) hydroxylation on the morpholine ring and (6) loss of the
      morpholine ring leading to metabolites containing either a hydroxylated or a
      carboxylated alkyl terminal. Three metabolites were identified as morpholinyl
      ring-opening products: M1, M6 and M13. Six metabolites (M2-M5, M7 and M8) were
      proposed to be the products of o-demethylation, hydroxylation on the
      methoxyphenyl group or the morpholinyl ring, dehydration following morpholinyl
      ring monohydroxylation, or a combination of the above metabolic pathways. The
      remaining eight metabolites were attributed to a pathway involving the loss of
      the morpholine ring at various points during the metabolic processes.

PMID- 15236307
TI  - Gas-phase ion chemistry in the ternary silane-propyne-phosphine system.
AB  - The gas-phase ion chemistry of propyne-phosphine and silane-propyne-phosphine
      mixtures was studied by ion trap mass spectrometry. For the binary mixture, the
      effect of different partial pressures of the reagents on the yield of C and P
      containing ions was evaluated. Reaction sequences and rate constants were
      determined and reaction efficiencies were calculated from comparison of
      experimental and collisional rate constants. In the ternary silane-propyne
      phosphine systems, the reaction pathways leading to formation of
      Si(m)C(n)P(p)H(q) (+) ions were determined and the rate constants of the most
      important steps were measured. For some ion species, selected by double isolation
      procedures (MS/MS), the low ion abundances prevented determination of the
      reaction rate constants. Si, C and P-containing ions are mainly produced in
      reactions of Si(m)P(p)H(q) (+) ions with propyne, while the reactivity of the
      Si(m)C(n)H(q) (+) ions towards PH(3) and of the C(n)P(p)H(q) (+) ions towards
      SiH(4) is very low. The formation of hydrogenated Si--C--P ions is interesting
      for their possible role as precursors of amorphous silicon carbides doped with
      phosphorus, obtained in a single step, by deposition from properly activated
      silane-propyne-phosphine mixtures.

PMID- 15236308
TI  - Oligosaccharide sequences in Quillaja saponins by electrospray ionization ion
      trap multiple-stage mass spectrometry.
AB  - Ten different samples with 13 previously identified saponin structures from
      Quillaja saponaria Molina were investigated by electrospray ionization ion trap
      multiple-stage mass spectrometry (ESI-ITMS(n)) in positive and negative ion
      modes. Both positive and negative ion mode MS(1)-MS(4) spectra were analyzed,
      showing that structural information on the two oligosaccharide parts in the
      saponin can be obtained from positive ion mode spectra whereas negative ion mode
      spectra mainly gave information on one of the oligosaccharide parts. Analysis of
      MS(1)-MS(4) spectra identified useful key fragment ions important for the
      structural elucidation of Quillaja saponins. A flowchart involving a stepwise
      procedure based on key fragments from MS(1)-MS(3) spectra was constructed for the
      identification of structural elements in the saponin. Peak intensity ratios in
      MS(3) spectra were found to be correlated with structural features of the
      investigated saponins and are therefore of value for the identification of
      terminal monosaccharide residues.

PMID- 15236310
TI  - Electrospray ionization mass spectrometric study of 1,3,4-thiadiazole-copper
      complexes: comparison with 1,3,4-oxadiazole derivatives.

PMID- 15236309
TI  - Effect of reverse scan on mass measurement accuracy in an ion trap mass
      spectrometer.

PMID- 15236311
TI  - Current literature in mass spectrometry.

PMID- 15236312
TI  - ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2
      mutation carriers.
AB  - Breast cancer risk is greatly increased in women who carry mutations in the BRCA1
      or BRCA2 genes. Because breast cancer initiation is different between BRCA1/2
      mutation carriers and women who do not carry mutations, it is possible that the
      mechanism of breast cancer progression is also different. Histopathologic and
      genetic studies have supported this hypothesis. To test this hypothesis further,
      we utilized a large cohort of women who underwent therapeutic mastectomy (TM) and
      contralateral prophylactic mastectomy (PM). From this cohort, we developed case
      groups of women with a family history of breast cancer with BRCA1/2 deleterious
      mutations, with unclassified variant alterations, and with no detected mutation
      and matched these cases with sporadic controls from the same TM and PM cohort.
      Fluorescence in situ hybridization was performed on paraffin sections by use of
      dual-color probes for ERBB2/CEP17, MYC/CEP8, TBX2/CEP17, and RPS6KB1/CEP17. All
      malignant and benign lesions, including putative precursor lesions, were studied.
      The invasive cancers from deleterious mutation carriers had a higher prevalence
      of duplication of MYC (P = 0.006) and TBX2 (P = 0.0008) compared to controls and
      a lower prevalence of ERBB2 amplification (P = 0.011). Coduplication of MYC and
      TBX2 was common in the in situ and invasive lesions from the deleterious mutation
      carriers. The odds ratio of having a BRCA1/2 mutation is 31.4 (95% CI = 1.7-569)
      when MYC and TBX2 are coduplicated but ERBB2 is normal. Unclassified variant
      carriers/no mutation detected and sporadic controls had a similar prevalence of
      alterations, suggesting that hereditary patients with no deleterious mutations
      follow a progression pathway similar to that of sporadic cases. With the
      exception of one atypical ductal hyperplasia lesion, no putative precursor lesion
      showed any detectable alteration of the probes tested. There was no significant
      intratumoral heterogeneity of genetic alterations. Our data confirm that a
      specific pattern of genomic instability characterizes BRCA1/2-related cancers and
      that this pattern has implications for the biology of these cancers. Moreover,
      our current and previous results emphasize the interaction between phenotype and
      genotype in BRCA1/2-related breast cancers and that a combination of morphologic
      features and alterations of ERBB2, MYC, and TBX2 may better define mechanisms of
      tumor progression, as well as determine which patients are more likely to carry
      BRCA1/2 mutations.

PMID- 15236313
TI  - Genomic context of paralogous recombination hotspots mediating recurrent NF1
      region microdeletion.
AB  - Recombination between paralogs that flank the NF1 gene at 17q11.2 typically
      results in a 1.5-Mb microdeletion that includes NF1 and at least 13 other genes.
      We show that the principal sequences responsible are two 51-kb blocks with 97.5%
      sequence identity (NF1REP-P1-51 and NF1REP-M-51). These blocks belong to a
      complex group of paralogs with three components on 17q11.2 and another on
      19p13.13. Breakpoint sequencing of deleted chromosomes from multiple patients
      revealed two paralogous recombination hot spots within the 51-kb blocks. Lack of
      sequence similarity between these sites failed to suggest or corroborate any
      putative cis-acting recombinogenic motifs. However, the NF1 REPs showed
      relatively high alignment mismatch between recombining paralogs, and we note that
      the NF1REP hot spots were regions of good alignment bordered by relatively large
      alignment gaps. Statistical tests for gene conversion detected a single
      significant tract of perfect match between the NF1REPs that was 700 bp long and
      coincided with PRS2, the predominant recombination hot spot. Tracts of perfect
      match occurring by chance may contribute to breakpoint localization, but our
      result suggests that perfect tracts at recombination hot spots may be a result of
      gene conversion at sites at which preferential pairing occurs for other, as-yet
      unknown reasons.

PMID- 15236314
TI  - Epigenetic regulation of human telomerase reverse transcriptase promoter activity
      during cellular differentiation.
AB  - The human telomerase reverse transcriptase (TERT) gene is transcriptionally
      inactivated in most differentiated cells but is reactivated in the majority of
      cancer cells. To elucidate how TERT is inactivated during differentiation, we
      applied all-trans retinoic acid (ATRA) to induce the differentiation of human
      teratocarcinoma (HT) cells and human acute myeloid leukemia (HL60) cells. We
      first showed that TERT promoter activity decreased rapidly, which preceded a
      gradual loss of endogenous telomerase activity following ATRA induction. To
      elucidate the underlying mechanisms of the reduced TERT promoter activity during
      differentiation, we performed epigenetic studies on the TERT promoter and found a
      progressive histone hypoacetylation coupled with a gradual accumulation of
      methylated cytosines in the TERT promoter. We also observed that the TERT
      promoter was less methylated in pluripotent HT cells than in multipotent HL60
      cells throughout a 12-day differentiation process. This origin-dependent
      epigenetic change was also confirmed in histone acetylation studies, indicating
      that the TERT promoter was more resistant to deacetylation in HT cells than in
      HL60 cells. Taken together, our results demonstrate synergistic involvement of
      DNA methylation and histone deacetylation in the down-regulation of TERT promoter
      activity that may be dependent on the origin of the cell types, and they add new
      insight into the way telomerase activity may be regulated during differentiation.

PMID- 15236315
TI  - Chromosomal instability and marker chromosome evolution in oral squamous cell
      carcinoma.
AB  - Squamous cell carcinoma of the head and neck and its subset, oral squamous cell
      carcinoma (OSCC), arise through a multistep process of genetic alterations as a
      result of exposure to environmental agents, such as tobacco smoke, alcoholic
      beverages, and viruses, including human papillomavirus. We and others have shown
      that the karyotypes of OSCC are near-triploid and contain multiple structural and
      numerical abnormalities. However, despite a background of clonal chromosomal
      aberrations, individual cells within a culture express many nonclonal numerical
      and structural abnormalities, termed chromosomal instability (CIN). To evaluate
      CIN in oral cancer cells, we isolated clones from two OSCC cell lines and carried
      out classical cytogenetic analysis, fluorescence in situ hybridization using
      centromere-specific probes, and spectral karyotyping. We observed variation in
      chromosome number within clones and between clones of the same cell line.
      Although similar numbers of centromeric signals for a particular chromosome were
      present, "homologs" of a chromosome varied structurally from cell to cell (marker
      chromosome evolution) as documented by classical and spectral karyotyping. In
      addition to the numerical chromosome variations within a clone, we observed
      marker chromosome evolution by structural chromosome alterations. It appears that
      both intrinsic structural alterations and extrinsic cytoskeletal factors
      influence chromosome segregation, resulting in individual tumor cells that
      express unique karyotypes. We show that CIN and marker chromosome evolution are
      essential acquired features of neoplastic cells. Proliferation of this
      heterogeneous cell population may provide some cells with the ability to evade
      standard therapies.

PMID- 15236316
TI  - Cytogenetic changes in nonmalignant breast tissue.
AB  - Cytogenetic changes are common in breast cancer and have also been described in
      fibroadenomas and fibrocystic disease, but not in histologically normal breast
      tissue. Cytogenetic analysis was performed on nonmalignant breast tissue from
      benign breast lumps (n = 8), reduction mammoplasties (n = 31), and grossly
      nontumorous tissue from cancerous breasts (n = 84), using standard techniques and
      G-banding. All samples were reviewed histologically. Clonal chromosomal changes
      were found in three of eight benign breast tumors (38%). Of the reduction
      mammoplasties, 17 samples contained nonproliferative changes, and three of these
      (18%) showed a clonal deletion of 3p. No pathology was identified in the other 14
      samples, of which one (7%) contained two clonal changes, apparently balanced
      translocations. Of nontumorous tissues from cancerous breasts, 15 (18%) showed
      clonal chromosomal abnormalities. Five of these samples were histologically
      normal. Two clones were identical to those found in the corresponding cancer. In
      18 additional samples, single cells were detected with the same change as that
      seen in clones or single cells in the cancer. Only 4 of these 20 samples
      contained detectable cancer cells. Clonal abnormalities found in two or more
      samples included trisomies X, 7, and 20 and monosomies 19 and 18. Clonal changes
      were not significantly more frequent in proliferative than in nonproliferative
      lesions. The Icelandic BRCA2 founder mutation, 999del5, was detected in four
      samples, all histologically normal, two of which had clonal chromosomal
      abnormalities. In conclusion, clonal chromosomal changes are not infrequent in
      nonmalignant breast tissue and can be detected even in the absence of
      histological abnormalities.

PMID- 15236317
TI  - Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor
      suppressor localized to a 9-Mb interval.
AB  - Loss of the short arm of chromosome 1 is frequently observed in many tumor types,
      including melanoma. We recently localized a third melanoma susceptibility locus
      to chromosome band 1p22. Critical recombinants in linked families localized the
      gene to a 15-Mb region between D1S430 and D1S2664. To map the locus more finely
      we have performed studies to assess allelic loss across the region in a panel of
      melanomas from 1p22-linked families, sporadic melanomas, and melanoma cell lines.
      Eighty percent of familial melanomas exhibited loss of heterozygosity (LOH)
      within the region, with a smallest region of overlapping deletions (SRO) of 9 Mb
      between D1S207 and D1S435. This high frequency of LOH makes it very likely that
      the susceptibility locus is a tumor suppressor. In sporadic tumors, four SROs
      were defined. SRO1 and SRO2 map within the critical recombinant and familial
      tumor region, indicating that one or the other is likely to harbor the
      susceptibility gene. However, SRO3 may also be significant because it overlaps
      with the markers with the highest 2-point LOD score (D1S2776), part of the
      linkage recombinant region, and the critical region defined in mesothelioma. The
      candidate genes PRKCL2 and GTF2B, within SRO2, and TGFBR3, CDC7, and EVI5, in a
      broad region encompassing SRO3, were screened in 1p22-linked melanoma kindreds,
      but no coding mutations were detected. Allelic loss in melanoma cell lines was
      significantly less frequent than in fresh tumors, indicating that this gene may
      not be involved late in progression, such as in overriding cellular senescence,
      necessary for the propagation of melanoma cells in culture.

PMID- 15236318
TI  - Prognostic classification of relapsing favorable histology Wilms tumor using cDNA
      microarray expression profiling and support vector machines.
AB  - Treatment of Wilms tumor has a high success rate, with some 85% of patients
      achieving long-term survival. However, late effects of treatment and management
      of relapse remain significant clinical problems. If accurate prognostic methods
      were available, effective risk-adapted therapies could be tailored to individual
      patients at diagnosis. Few molecular prognostic markers for Wilms tumor are
      currently defined, though previous studies have linked allele loss on 1p or 16q,
      genomic gain of 1q, and overexpression from 1q with an increased risk of relapse.
      To identify specific patterns of gene expression that are predictive of relapse,
      we used high-density (30 k) cDNA microarrays to analyze RNA samples from 27
      favorable histology Wilms tumors taken from primary nephrectomies at the time of
      initial diagnosis. Thirteen of these tumors relapsed within 2 years. Genes
      differentially expressed between the relapsing and nonrelapsing tumor classes
      were identified by statistical scoring (t test). These genes encode proteins with
      diverse molecular functions, including transcription factors, developmental
      regulators, apoptotic factors, and signaling molecules. Use of a support vector
      machine classifier, feature selection, and test evaluation using cross-validation
      led to identification of a generalizable expression signature, a small subset of
      genes whose expression potentially can be used to predict tumor outcome in new
      samples. Similar methods were used to identify genes that are differentially
      expressed between tumors with and without genomic 1q gain. This set of
      discriminators was highly enriched in genes on 1q, indicating close agreement
      between data obtained from expression profiling with data from genomic copy
      number analyses.

PMID- 15236319
TI  - Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic
      loss of TSC1 or TSC2.
AB  - Chordomas are rare sacrococcygeal/sacral, sphenooccipital/clivus, and spinal
      tumors whose molecular etiology remains relatively understudied. As several
      anecdotal reports had described chordomas in individuals with tuberous sclerosis
      complex (TSC), a multisystem hamartoma syndrome, we hypothesized that the genes
      that cause TSC may have an etiological role in chordomas. In two cases of
      sacrococcygeal chordomas in individuals with TSC, one with a germ-line TSC2
      mutation and the other with a germ-line TSC1 mutation, we confirmed somatic
      inactivation of the corresponding wild-type allele by loss of heterozygosity
      analysis and immunohistochemistry. These data provide the first evidence of a
      pathogenic role by TSC genes in sacrococcygeal chordomas.

PMID- 15236320
TI  - Insertions generating the 5'RUNX1/3'CBFA2T1 gene in acute myeloid leukemia cases
      show variable breakpoints.
AB  - Translocation t(8;21)(q22;q22) is a common karyotypic abnormality detected in
      about 15% of acute myeloid leukemia (AML) cases. The rearrangement results in
      fusion of the RUNX1 (also known as AML1) and CBFA2T1 (also known as ETO) genes,
      generating a 5'RUNX1/3'CBFA2T1 transcriptionally active fusion gene on derivative
      chromosome 8, but some cases with ins(21;8) and ins(8;21) have been observed.
      However, a detailed breakpoint characterization of the insertion events has never
      been reported. In the present article, we describe six insertion events among 82
      (7.3%) AML cases characterized by the RUNX1/CBFA2T1 fusion. Using FISH
      experiments with appropriate bacterial artificial chromosome (BAC) and P1
      artificial chromosome (PAC) probes, we were able to perform a detailed molecular
      cytogenetic characterization of one case with ins(8;21) and five with ins(21;8).
      Our analysis revealed that insertions generating the 5'RUNX1/3'CBFA2T1 gene
      showed variable breakpoints; the size of the inserted elements ranged from 2.4 to
      44 Mb.

PMID- 15236321
TI  - Complementary DNA cloning of rat spetex-1, a spermatid-expressing gene-1,
      encoding a 63 kDa cytoplasmic protein of elongate spermatids.
AB  - We used differential display in combination with complementary DNA (cDNA) cloning
      approach to isolate a novel rat gene designated as spetex-1, which had an open
      reading frame of 1,668-length nucleotides encoding a protein of 556 amino acids.
      Spetex-1 mRNA was highly expressed in testis, and weekly expressed in lung,
      intestine, and spleen. Spetex-1 expression in the rat testes was detected first
      at 3 weeks in postnatal development and continued to be detected up to adulthood.
      A search in the databases showed that the amino acid sequence of spetex-1 was 82%
      identical to that of its mouse homologue found in the databases. Both rat spetex
      1 and the mouse homologue contained Ser-X (X = His, Arg, or Asn) repeats in the
      middle portion of the proteins. In situ hybridization revealed that spetex-1 mRNA
      was expressed in haploid spermatids of step 7-18 within the seminiferous
      epithelium. Immunohistochemical analysis with confocal laser-scanning microscopy
      demonstrated that spetex-1 protein was not expressed in spermatogonia,
      spermatocytes, and round spermatids in adult rat testis, but was specifically
      detected in the residual cytoplasm of elongate spermatids of step 15-18 as well
      as in residual bodies engulfed by Sertoli cells. We interpreted these data as a
      potential role of spetex-1 in spermatogenesis, especially in cell differentiation
      from late elongate spermatids to mature spermatozoa.

PMID- 15236322
TI  - Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor
      germ cell nuclear factor and CREMtau.
AB  - Germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily,
      which is expressed in the adult predominantly in the male and female germ cells.
      In the male, GCNF is expressed in spermatogenic cells. GCNF binds as a homodimer
      to direct repeat response elements of the consensus half-site sequence, AGGTCA,
      with 0 bp spacing (DR0). Using this information, a search of genomic databases
      was performed to identify candidate GCNF responsive, spermatogenic-specific,
      genes that contain DR0 sequences. The mouse protamine genes are the strongest
      candidates identified to date, as they are post-meiotically expressed in round
      spermatids and contain DR0 elements in their proximal promoters. Previous work
      has shown that both recombinant and endogenous GCNF bind to DR0 elements in the
      mouse protamine 1 and 2 (Prm 1 and Prm 2) promoters with high affinity and
      specificity. The present work shows that in transient transfection assays in GC-1
      and JEG-3 cells, co-transfection of a GCNF-VP16 expression plasmid with reporter
      plasmids containing either the wild type Prm 1 or Prm 2 promoter established that
      GCNF-VP16 is able to regulate transcription from both promoters in a DR0
      dependent manner. Wild type GCNF, in contrast, acts as a repressor of basal
      transcription on both the Prm 1 and Prm 2 promoters in a DR0-dependent manner.
      Furthermore, CREMtau activation of these promoters is also repressed by wild-type
      GCNF, indicating that GCNF also acts as a repressor of activated transcription.
      GCNF therefore defines a novel nuclear receptor-signaling pathway that may
      regulate a subset of genes involved in the terminal differentiation process of
      spermatogenesis, exemplified by the protamines.

PMID- 15236323
TI  - Increased formation of corpora lutea in neurokinin 1-receptor deficient mice.
AB  - There is evidence to suggest that the tachykinin-receptor system may be involved
      in female reproduction. Recently, we have shown that the mRNA transcripts of the
      preprotachykinin-A which encodes substance P (SP), a member of the tachykinin
      family, and of NK1-R (preferred receptor of SP) are expressed in the bovine
      corpus luteum (CL) of early developmental stage. The question arises whether the
      system is expressed at the protein level and influences the ovulatory process and
      CL formation. For this reason, ovaries from a mouse mutant in which the NK1-R
      gene had been disrupted were studied. By using RT-PCR, mRNA expression of NK1-R
      was confirmed in both the ovary and the uterus of wild-type mice. Weaning
      frequency and litter size, as recorded over 6 months, were similar in both
      groups. However, counting of CL in serial paraffin sections revealed a
      significant higher number of CL in the NK1-R deficient mice in comparison to the
      wild-type group (P < 0.01). The increased formation of CL in NK1-R deficient mice
      corresponded to a considerable number of CL with retained oocyte not found in
      ovaries of the wild-type group. We conclude: The CL with a retained oocyte may
      indicate that the muscular apparatus of the preovulatory follicle plays a role in
      oocyte expulsion and that contractility of the follicle wall is deficient in the
      mutant group. Our observation may have implications for the luteinized unruptured
      follicle syndrome in humans.

PMID- 15236324
TI  - Identification and analysis of stage-specific expression of lysosome-associated
      protein transmembrane 4alpha gene during development of preimplantation rabbit
      nuclear transfer embryo.
AB  - The stage-specific expression of Lysosome-associated protein transmembrane 4alpha
      (LAPTM4alpha) in preimplantation rabbit nuclear transfer (NT) embryo was
      identified with the DDRT-PCR and reverse Northern Blot. The full length (1,364
      bp) cDNA of LAPTM4alpha was screened out from cDNA library constructed with
      rabbit ovary and in situ hybridization (ISH) was used to trace the distribution
      of the LAPTM4alpha mRNA in intra-ovary, especially the follicle which proved that
      the LAPTM4alpha gene expression is involved in the follicles development,
      maturation, ovulation, luteinization, and preimplantation development in the
      rabbit (Oryctolagus cuniculus domestica). To our knowledge, this is the first
      characterization of LAPTM4alpha gene expression and mRNA distribution in the
      rabbit ovary and first evidence for this gene involving in follicle development
      and rabbit preimplantation development.

PMID- 15236325
TI  - Germ cells enter meiosis in a rostro-caudal wave during development of the mouse
      ovary.
AB  - Germ cells in the mouse embryo remain undifferentiated until about 13.5 days post
      coitum (dpc), when male germ cells enter mitotic arrest and female germ cells
      enter meiosis. The molecular signals and transcriptional control mechanisms
      governing the differential fate of germ cells in males and females remain largely
      unknown. In order to gain insights into the behavior of germ cells around this
      period and into likely mechanisms controlling entry into meiosis, we have studied
      by wholemount in situ hybridization the expression pattern of two germ cell
      specific markers, Oct4 and Sycp3, during mouse fetal gonad development. We
      observed a dynamic wave of expression of both genes in developing ovaries, with
      Oct4 expression being extinguished in a rostro-caudal wave and Sycp3 being
      upregulated in a corresponding wave, during the period 13.5-15.5 dpc. These
      results indicate that entry into meiosis proceeds in a rostro-caudal progression,
      in turn suggesting that somatically derived signals may contribute to the control
      of germ cell entry into meiosis in developing ovaries.

PMID- 15236326
TI  - Retrovirus-mediated gene transfer and expression of EGFP in chicken.
AB  - Here, we successfully demonstrate expression of the EGFP (enhanced green
      fluorescence protein) gene in chickens using replication-defective MLV (murine
      leukemia virus)-based retrovirus vectors encapsidated with VSV-G (vesicular
      stomatitis virus G glycoprotein). The recombinant retrovirus was injected beneath
      the blastoderm of non-incubated chicken embryos (stage X). After 12 days
      incubation, all of the eight living embryos assayed were found to express this
      vector-encoded EGFP gene, which was under the control of the RSV (Rous Sarcoma
      Virus) promoter, in diverse organ tissues, including head, beak, neck, wing,
      hock, tail, toes, heart, amnion, and yolk sac. Surprisingly, despite the presumed
      cytotoxicity of EGFP, some embryos hatched and survived and these had prominent
      green fluorescent spots, both in internal organs and externally.

PMID- 15236327
TI  - Production of transgenic chimeric rabbits and transmission of the transgene
      through the germline.
AB  - Here we report that improved reproductive technologies combined with an efficient
      microinjection method and in vitro cultivation medium enabled us to create germ
      line chimeric rabbits. To follow the fate of the chimeric embryo a blastomere
      marked with the human blood coagulation factor VIII (hFVIII) transgene was
      microinjected into a morula stage wild type embryo. The degree of chimerism in
      different tissues was estimated by real-time PCR and was found to be in the range
      of 0.1-42%. Among the four chimeric animals, one was identified as a chromosomal
      intersex and two were germline chimeras.

PMID- 15236328
TI  - Effect of speed of development on mRNA expression pattern in early bovine embryos
      cultured in vivo or in vitro.
AB  - Recent data have demonstrated that fast-cleaving embryos produced in vitro are
      more likely to develop to blastocyst stage, and that the postfertilization
      culture system used impacts considerably on the mRNA expression and quality of
      blastocysts produced. The present study is the first to investigate the
      relationship between the developmental speed of embryos produced in vivo or in
      vitro and the temporal transcription pattern. Genes related to important
      preimplantation events are monitored during the first 4 days of embryo
      development in embryos with fast or slow development. The set of genes analyzed
      in the present study characterizes several important physiological processes
      including: transport and metabolism of fructose (Glut-5), stress (SOX),
      mitochondrial activity and detoxification of reactive oxygen species (MnSOD),
      cell communication (Cx43), maternal recognition of pregnancy (IFN-tau),
      imprinting (IGF-II), apoptosis (Bax), growth factor binding and metabolism (IGF
      IR), and oxidative stress (G6PD). Using real time PCR, we have found that for all
      the genes analyzed there are differences in mRNA expression between embryos with
      fast and slow developmental speed produced both in vitro and in vivo. Frequently,
      genes that may be stress induced such as SOX, MnSOD, BAX, IFtau, and G6PD were
      highly transcribed in in vitro produced embryos and in embryos with slow
      developmental speed. On the other side, transcripts from genes related with
      metabolism, growth, and differentiation (Glut-5, Cx 43, IGF-II, and IGF-IR) were
      detected in higher amounts in in vivo produced embryos and in embryos with fast
      developmental speed. Moreover, it is interesting to stand out that for some
      genetic markers (such as SOX and G6PD) there are in vivo and in vitro differences
      that can be observed even before materno-zygotic transition, which probably
      reflects a differential mRNA degradation. These transcription patterns reflects
      the embryonic response to the adverse in vitro culture conditions, and connect
      the low quality of embryos which slow developmental speed produced in vivo and in
      vitro, with the mRNA expression pattern of some embryonic genes.

PMID- 15236329
TI  - Intracytoplasmic sperm injection of frozen-thawed bovine oocytes and subsequent
      embryo development.
AB  - Oocyte cryopreservation and intracytoplasmic sperm injection (ICSI) are
      advantageous to expand their usefulness in genetic engineering. Oocytes matured
      for 22 hr were vitrified in droplets of cryoprotectants (3.2 M ethylene glycol
      (EG), 2.36 M dimethyl sulfoxide (DMSO), 0.6 M sucrose) on copper electron
      microscope (EM) grids. After being warmed, the oocytes were cultured in IVM
      medium for an additional 2 hr. Sperm treated with dithiothreitol were utilized
      for ICSI. Oocytes injected with sperm were activated by combination of ionomycin
      with cycloheximide (CHX). The ICSI oocytes were compared for the rates of
      pronuclear formation, development, cell number, and the ratio of ICM to those of
      fresh ICSI and IVF control. The proportion of 2PN formation was significantly
      higher in IVF control (Group 1) than those in other treated groups. Among the
      treated groups a significant lower 2PN formation was observed in IVF-frozen
      thawed than in ICSI-fresh and frozen-thawed groups. Cleavage rates in IVF-frozen
      thawed and ICSI-frozen-thawed groups were significantly lower than those of IVF
      control and ICSI-fresh groups. In ICSI groups, the rates of cleavage and
      blastocyst in fresh oocytes were significantly higher than in frozen-thawed.
      Development rates into blastocysts in the ICSI-fresh and frozen-thawed groups
      were significantly lower than that of IVF control. Total cell number was
      significantly lower in both frozen-thawed IVF and ICSI groups than those in IVF
      control and ICSI-fresh groups. However, the rates of the remaining cells that
      were found in the ICM were significantly higher in both frozen-thawed IVF and
      ICSI than in the IVF-control and ICSI-fresh groups. The results indicated that
      frozen-thawed bovine oocytes were suitable for ICSI procedure.

PMID- 15236330
TI  - VEGF, bFGF, and their receptors in the endometrium of rhesus monkey during
      menstrual cycle and early pregnancy.
AB  - A number of cytokines and growth factors are known to modulate proliferation and
      differentiation of human endometrium. In this study, the expression of vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and VEGF
      receptors, fms-like tyrosine kinase (Flt1) and kinase insert domain-containing
      region (KDR), and bFGF receptor 1 (Flg) were examined in the endometrium of
      rhesus monkey on Day 5, 10, 16, 20, 25 of menstrual cycle and on Day 19 of early
      pregnancy. Western blot analysis showed the specificity of the anti-human
      antibodies with the monkey tissue. The expression of mRNA and protein of VEGF was
      correlated with that of its receptor KDR, which was detected in epithelial,
      vascular, and myometrial cells. The localization of bFGF and its receptor Flg was
      similar to that of VEGF, except that the Flg was absent in the endothelial cells.
      Strong expression of VEGF and bFGF in the glandular epithelial cells was observed
      in the proliferative phase, declined in the secretory phase during the cycle.
      Stronger staining of these factors was also observed in the decidual cells of the
      pregnant uterus, as compared with the stromal cells of cycling uterus. No
      expression of Flt1 was detected in the tissue examined in this study. These data
      suggest that VEGF, bFGF, and their receptors play important roles in epithelial
      and stromal development, angiogenesis, and blood vessel function in the
      endometrium during the menstrual cycle and early pregnancy of the rhesus monkey.

PMID- 15236331
TI  - Investigation of estrogen receptor alpha and beta mRNA expression in the pregnant
      rat uterus.
AB  - Although the expressions of the estrogen receptor (ER) subtypes have been
      demonstrated in a large number of estrogen target tissues, to date no evidence
      has been reported as to how the expressions of the alpha (alpha) and beta (beta)
      ER subtype mRNA alter in the rat uterus during pregnancy. The aims of the present
      study were to obtain information concerning the changes in the ER and the
      progesterone receptor (PR) in early pregnancy and to determine the alterations in
      the ER subtype mRNA in the pregnant rat uterus. To demonstrate the ER and PR
      densities, radioligand saturation assay was used. The reverse-transcription
      polymerase chain reaction (RT-PCR) was applied to characterize the alterations in
      the ER subtype mRNA. ER expression was highest on day 5 of pregnancy (Bmax =
      637.40 +/- 76.10 fmol/mg). The PR expression did not change significantly until
      day 8, but the protein density was increased on day 8 of pregnancy. The ERalpha
      mRNA expression was active during pregnancy, maximum expression was attained on
      day 5; a gradual decrease was then observed until the second half of pregnancy
      when its expression continuously increased up to the day of labor (day 22). Since
      the attachment of the blastocyst, an event that is dependent on estradiol in the
      progesterone-primed uterus of the rat, occurs on day 5 of pregnancy and the
      levels of the ER protein and the ERalpha mRNA on day 5 of pregnancy was the
      highest, it could be supposed that this subtype of ER might regulate
      implantation. The ERbeta mRNA was detected only from day 7 to day 15, with a
      maximum level on day 8. The expression of this ER subtype might be related to the
      development of decidual tissue.

PMID- 15236332
TI  - Study of the mouse sortilin gene: Effects of its transient silencing by RNA
      interference in TM4 Sertoli cells.
AB  - Using databases of the mouse genome in combination with a sequence deduced from a
      mouse sortilin cDNA originated in our laboratory, we found the sortilin gene to
      map to a region of chromosome 3. The mouse sortilin gene contains 19 short exons
      separated by introns of various sizes. The study elucidated the exon-intron
      boundaries. Some introns extend over more than 24 kb. In the cytoplasmic domain
      of the translation product, we found a dileucine motif and three other motifs
      known to constitute the active sorting signal of the mannose 6-phosphate receptor
      (M6P-R). We also tested the hypothesis that sortilin is involved in the sorting
      of prosaposin (SGP-1) to the lysosomes. Prosaposin was initially identified in
      Sertoli cells, found in large amounts in the lysosomal compartment and implicated
      in the degradation of residual bodies released by the spermatids during
      spermiation. Interestingly, the targeting of prosaposin to the lysosomes is
      independent of the M6P-R. This investigation demonstrated that sortilin was
      required for the trafficking of prosaposin to the lysosomes in TM4 cells. The
      requirement of sortilin was shown using a siRNA probe to block the translation of
      sortilin mRNA. Sortilin-deficient cells were not able to route prosaposin to the
      lysosomal compartment but continue to transport cathepsin B, since this hydrolase
      uses the M6P-R to be routed to the lysosomes. These results indicate that
      sortilin appears to be involved in the lysosomal trafficking of prosaposin.

PMID- 15236333
TI  - The trafficking of prosaposin (SGP-1) and GM2AP to the lysosomes of TM4 Sertoli
      cells is mediated by sortilin and monomeric adaptor proteins.
AB  - Prosaposin (SGP-1) and GM2 activator protein (GM2AP) are soluble sphingolipid
      activator proteins (SAPs) that are targeted to the lysosomal compartment of
      Sertoli cells to aid hydrolases in the breakdown of glycosphingolipids. To reach
      the lysosome, most soluble proteins must interact with the mannose 6-phosphate
      receptor (MPR). To be sorted from the Golgi, the MPR must bind to the Golgi
      associated, gamma-adaptin homologous, ARF binding proteins (GGAs), a group of
      monomeric adaptor proteins responsible for the recruitment of clathrin. It is
      well established, however, that the lysosomes of I-cell disease (ICD) patients
      have near normal levels of several lysosomal proteins, including prosaposin and
      GM2AP. ICD results from a mutation in the phosphotransferase that adds mannose 6
      phosphate to hydrolases. Thus, prosaposin and GM2AP can traffic to lysosomes in a
      MPR independent manner. Previous work has demonstrated that an interaction with
      sphingomyelin in the Golgi membrane is necessary for the targeting of prosaposin
      by an unknown receptor. Using a TM4 Sertoli cell line, we tested the hypothesis
      that prosaposin and GM2AP are targeted to the lysosomal compartment via the
      sortilin receptor, which has been recently shown to have a GGA binding motif.
      Interestingly, dominant-negative GGAs, unable to bind clathrin to shuttle from
      the Golgi, prevented the trafficking of prosaposin and GM2AP to lysosomes. A
      dominant negative construct of sortilin lacking the GGA binding domain retained
      prosaposin and GM2AP in the Golgi. In conclusion, our results showed that the
      trafficking of prosaposin and GM2AP to the lysosome is dependent on sortilin.

PMID- 15236334
TI  - Relationship between the morphological changes of somatic compartment and the
      kinetics of nuclear and cytoplasmic maturation of oocytes during in vitro
      maturation of porcine follicular oocytes.
AB  - Based on the morphology and expansion of the cumulus cells, several different
      classes of porcine cumulus-oocyte complexes (COCs) can be distinguished, during
      their maturation in vitro. The goal of the present study was to find out the rate
      of each morphologic category in case of COCs and granulosa-cumulus-oocyte
      complexes (GCOCs), the characteristics of their nuclear progression, cytoplasmic
      maturation, and the frequency of monospermy after IVF. It was found that the
      frequency of cumulus expansion is higher in case of GCOCs than that of COCs.
      Nuclear progression of COCs was more accelerated than that of GCOCs. Oocytes
      attached to the bottom of culture dish with dark, compact cumulus underwent
      nuclear and acquired their ability to be activated earlier than that of oocytes
      showing normal cumulus expansion. The rate of monospermic fertilization after IVF
      of normal COCs showing normal cumulus expansion was higher than that of COCs
      attached to the dish. These results suggest that diverse behavior of cumulus
      cells during in vitro culture affects nuclear and cytoplasmic maturation of
      porcine oocytes, which also affects IVF results. It can be concluded that
      granulosa cells promote normal cumulus expansion thus decrease heterogeneity in
      nuclear and cytoplasmic maturation amongst oocytes.

PMID- 15236335
TI  - Carbohydrates and glycoproteins involved in bovine fertilization in vitro.
AB  - In the present study, efforts were made towards identifying carbohydrates and
      glycoproteins involved in bovine in vitro fertilization (IVF). In vitro matured
      cumulus-oocyte complexes (COCs) were inseminated in the presence of a variety of
      carbohydrates and glycoproteins to determine which glycoconjugates act as
      competitive inhibitors of oocyte penetration. Among the carbohydrates and
      glycoproteins tested, D-mannose, fucoidan, dextran sulfate, and fibronectin were
      the most potent inhibitors of oocyte penetration (90% or more inhibition), while
      L-fucose and vitronectin inhibited the penetration rate to a lesser extent
      (around 50% inhibition). Other carbohydrates caused less than 40% inhibition
      (i.e., D-galactose, N-acetyl-D-galactosamine, D-fucose, and sialic acid) or were
      not effective as inhibitors of oocyte penetration (i.e., mannan, N-acetyl-D
      glucosamine, dextran, and heparan sulfate). Heparin was the only carbohydrate
      that significantly increased the penetration rate. To exclude a possible toxic
      effect on spermatozoa, sperm motility was evaluated over time by means of
      computer-assisted sperm analysis in the presence of carbohydrates and/or
      glycoproteins that inhibited the penetration rate with 40% or more. L-fucose,
      dextran sulfate, and vitronectin did not significantly influence total and
      progressive sperm motility, whereas D-mannose, fucoidan, and fibronectin caused a
      significant, but slight reduction in both motility parameters. These results are
      indicative for the involvement of D-mannose, L-fucose, fucoidan, dextran sulfate,
      fibronectin, and vitronectin in bovine IVF.

PMID- 15236336
TI  - CASK is in the mammalian sperm head and is processed during epididymal
      maturation.
AB  - Upon adhesion to the zona pellucida or egg extracellular matrix, sperm undergo
      regulated exocytosis of the acrosomal vesicle. CASK is an adaptor protein that
      has been implicated in coupling neuronal cell adhesion to regulated exocytosis.
      In neurons, this scaffolding molecule is associated with several types of
      transmembrane receptor complexes and connects cell adhesion molecules with ion
      channels, the actin cytoskeleton, and the cell's exocytotic machinery. We
      hypothesized CASK might also be an important link between zona pellucida binding
      and the sperm acrosome reaction. RT-PCR experiments indicated CASK is transcribed
      in mouse testis. The full size (120 kDa) CASK protein was present in testis from
      mouse and pig. Immunoblots of mature porcine and murine sperm revealed that the
      120 kDa molecule was much less abundant than in testis but the antibody also
      recognized a group of smaller proteins migrating at 55-65 kDa. Immunofluorescence
      experiments indicated both the full length and smaller CASK immunoreactive
      products were found only in the acrosomal region of spermatids and mature sperm
      and not in other testicular cell types. CASK immunofluorescence was lost
      following the acrosome reaction. During epididymal maturation, the abundance of
      the full size CASK decreased and the CASK fragments increased. These results
      suggest that CASK may be proteolytically processed during epididymal maturation.
      Because sperm acquire the ability to bind the zona pellucida, acrosome react, and
      fertilize eggs during epididymal maturation, CASK processing may play a role in
      the acquisition of these functions.

PMID- 15236337
TI  - Distribution of prepubertal and adult goat oocyte cortical granules during
      meiotic maturation and fertilisation: ultrastructural and cytochemical study.
AB  - The aim of this study was evaluate cortical granule (CG) distribution during in
      vitro maturation (IVM) and fertilisation of prepubertal goat oocytes compared to
      CG distribution of ovulated and in vitro fertilised oocytes from adult goats.
      Oocytes from prepubertal goats were recovered from a slaughterhouse and were
      matured in M199 with hormones and serum for 27 hr. Ovulated oocytes were
      collected from gonadotrophin treated Murciana goats. Frozen-thawed spermatozoa
      were selected by centrifugation in percoll gradient and were capacitated in DMH
      with 20% steer serum for 1 hr. Ovulated and IVM-oocytes were inseminated in DMH
      medium with steer serum and calcium lactate for 20 hr. Oocytes and presumptive
      zygotes were stained with FITC-LCA (Lens culinaris agglutinin labelled with
      fluorescein isothiocyanate) and observed under a confocal laser scanning
      microscope. Ultrastructure morphology of oocytes and presumptive zygotes were
      analysed by transmission electron microscopy (TEM). Prepubertal goat oocytes at
      germinal vesicle stage show a homogeneous CG distribution in the cytoplasm. IVM
      oocytes at Metaphase II (MII) and ovulated oocytes presented CGs located in the
      cortex with the formation of a monolayer beneath to the plasma membrane. At 20 hr
      postinsemination (hpi), zygotes from IVM-oocytes showed a complete CG exocytosis
      whereas zygotes from ovulated oocytes presented aggregates of CGs located at the
      cortical region. Images by TEM detected that CGs were more electrodense and
      compacts in oocytes from prepubertal than from adult goats.

PMID- 15236338
TI  - Evidence that P36, a human sperm acrosomal antigen involved in the fertilization
      process is triosephosphate isomerase.
AB  - P36 is one of the immunodominant sperm antigens identified by antibodies eluted
      from the spermatozoa of infertile men. In a previous study, we isolated and
      characterized this auto-antigen as a glycoprotein with several isoforms. Specific
      rabbit antibodies were produced to investigate sperm topography and the role of
      P36 in the fertilization process and we showed that P36 is present on the
      equatorial segment of acrosome-reacted spermatozoa and is involved in sperm
      binding and the penetration of zona-free hamster oocytes. In the present study,
      we demonstrated, by means of immunofluorescence and electron microscopy, that P36
      is present all over the acrosomal membranes of non-reacted spermatozoa. We also
      investigated the role of P36 in the acrosome reaction and sperm binding to the
      zona pellucida (ZP). The exposure of capacitated spermatozoa to rabbit anti-P36
      antibodies had no effect on primary fixation to the ZP, but inhibited secondary
      binding to the ZP and the Ca2+ ionophore-induced acrosome reaction. These results
      suggest that P36, an acrosomal antigen, is involved in several steps of the
      fertilization process. On two-dimensional Western blots, human anti-sperm
      antibodies (ASA) and rabbit anti-P36 antibodies recognized five to six isoforms
      of P36, all 36/37 kDa in size, with a pI between 5.1 and 5.7. Two major spots
      were identified as human triosephosphate isomerase (TPI) by MALDI-TOF mass
      spectrometry. Anti-TPI antibodies were shown to react with the isoforms
      recognized by human and rabbit anti-P36 antibodies. We also demonstrated the
      presence of TPI in human sperm heads. Further studies are underway to establish
      whether there is a sperm-specific isoform of TPI and its role in sperm function.

PMID- 15236339
TI  - Distribution of terminal sugar residues in the testis of the spotted ray Torpedo
      marmorata.
AB  - Lectins represent a class of proteins/glycoproteins binding specifically to
      terminal sugar residues. The present investigation aims to identify lectin
      binding sites in testis of Torpedo marmorata. Using a panel of lectins coupled
      with fluoresceine isothiocyanate, we demonstrated that germ and somatic cells
      present in Torpedo testis contain glycoconjugates, whose distribution at the
      level of the surface, the cytoplasm and the nucleus changes during germ cell
      differentiation. Moreover our observations demonstrate that the germ cells
      undergoing apoptosis (Prisco et al., 2003a: Mol Reprod Dev 64:341-348)
      overexpress a residual sugar recognised by WFA lectin that can be considered a
      specific marker for apoptotic germ cells. Finally, our results indicate that
      there is a progressive increase in glycosilation during spermatogenesis,
      especially at the level of the acrosome in the spermatocyte-spermatid step, and
      that Leydig cells are differently stained in relation to the spermatogenetic
      cycle.

PMID- 15236340
TI  - Structure and unexpected chiroptical properties of chiral 4-pyrrolidinyl
      substituted 2(5H)-furanones.
AB  - Planar 2(5H)-furanones substituted at C4 with a chiral pyrrolidinyl group show CD
      spectra which are apparently due to the distortion of the C4-N1 bond of sp2
      character from the plane defined by the 2(5H)-furanone ring atoms and/or due to
      the presence of substituents in the pyrrolidine ring. This is a new, previously
      not encountered structural factor determining the chiroptical properties of 2(5H)
      furanones and emerging from the analysis of X-ray diffraction data and quantum
      mechanical DFT computations. In the presence of a C5 pseudoaxial substituent in
      the furanone ring, the sign of the furanone n-pi* and pi-pi* transition Cotton
      effects is determined primarily by the previously postulated allylic helicity
      rule.

PMID- 15236341
TI  - Stereoselectivity in formation of oxacephams from 1,3-alkylidene-threitols.
AB  - The [2+2]cycloaddition of CSI to the (Z)-propenyl ethers derived from respective
      1,3-methylidene- and 1,3-ethylidene-threitols, contrary to the corresponding
      erythritol derivatives, is characterized by a low stereoselectivity and a lack of
      stereospecificity. On the other hand, the alternative method of the oxacepham
      formation, based on the 4-vinyloxy-azetidinone, proceeds with an excellent
      stereoselectivity. The CD-spectroscopy offers an attractive tool for
      determination of the absolute configuration of the bridgehead carbon atom at the
      5-oxacepham skeleton.

PMID- 15236342
TI  - Structural determinations by circular dichroism spectra analysis using coupled
      oscillator methods: an update of the applications of the DeVoe polarizability
      model.
AB  - The exciton (coupled oscillator) model for optical activity is a very useful and
      powerful method which allows to analyze a circular dichroism (CD) spectrum in a
      nonempirical way, arriving at a safe assignment of the absolute configuration of
      organic and inorganic compounds. Usually in this model only the exciton coupling
      of two electrically allowed transitions (oscillators) is taken into account. This
      approach has the important advantage of an easy application but, sometimes, it
      may lead to wrong results. Thus, in this review article a more general treatment,
      which allows considering the simultaneous coupling of several oscillators, i.e.,
      the DeVoe model, is presented and critically analyzed, discussing in detail the
      latest applications reported in the literature. In the authors opinion, since the
      DeVoe model joins generality and reliability requiring an almost negligible
      computational effort, it represents the method of choice for stereochemical
      assignments, even by nonspecialists.

PMID- 15236343
TI  - Synthesis, theoretical and structural analyses, and enantiopharmacology of 3
      carboxy homologs of AMPA.
AB  - We have previously used homologation of (S)-glutamic acid (Glu) and Glu analogs
      as an approach to the design of selective ligands for different subtypes of Glu
      receptors. (RS)-2-Amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA),
      which is an isoxazole homolog of Glu, is a very potent agonist at the (RS)-2
      amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) subgroup of Glu
      receptors and a moderately potent ligand for the kainic acid (KA) subgroup of Glu
      receptors. The enantiomers of ACPA were previously obtained by chiral HPLC
      resolution. Prompted by pharmacological interest in ACPA, we have now prepared
      the (S)- and (R)-enantiomers of ACPA by stereocontrolled syntheses using
      (1R,2R,5R)- and (1S,2S,5S)-2-hydroxy-3-pinanone, respectively, as chiral
      auxiliaries. Furthermore, the 5-ethyl analog of ACPA, Ethyl-ACPA, was
      synthesized, and (S)- and (R)-Ethyl-ACPA were also prepared using this method.
      The absolute configurations of (S)- and (R)-ACPA were established by X-ray
      crystallographic analysis of a protected (1S,2S,5S)-2-hydroxy-3-pinanone imine
      derivative of (R)-ACPA. The absolute stereochemistry of (S)- and (R)-Ethyl-ACPA
      was assigned on the basis of a comparison of their properties with those of the
      enantiomers of ACPA, employing elution order on chiral HPLC columns, as well as
      circular dichroism (CD) spectroscopy in combination with time-dependent density
      functional theory. The structural and electronic basis for the Cotton effect
      observed for such analogs is examined. The lower homolog of ACPA, (RS)-2-amino-2
      (3-carboxy-5-methyl-4-isoxazolyl)acetic acid (1), which is a Glu analog, was also
      synthesized. Affinities and neuroexcitatory effects were determined using rat
      brain membranes and cortical wedges, respectively, at native AMPA, KA, and N
      methyl-D-aspartic acid (NMDA) receptors. The molecular pharmacology of (S)- and
      (R)-ACPA and (S)- and (R)-Ethyl-ACPA was evaluated at homomeric cloned subtypes
      of AMPA receptors (iGluR1o,3o,4o) and of KA receptors (iGluR5,6), expressed in
      Xenopus laevis oocytes. The cloned receptors mGluR1alpha, mGluR2, and mGluR4a,
      expressed in CHO cell lines, were used to study the effects of the five compounds
      at metabotropic Glu receptors. In accordance with ligand-receptor complexes known
      from X-ray crystallography, the conformationally restricted Glu analog 1 was
      inactive at all Glu receptors studied, and the R-forms of ACPA and Ethyl-ACPA
      were very weak or inactive at these receptors. At AMPA receptor subtypes, (S)
      ACPA and (S)-Ethyl-ACPA showed equally potent agonist effects at iGluR1o and
      iGluR3o, whereas (S)-Ethyl-ACPA was 6-fold more potent than (S)-ACPA at iGluR4o.
      (S)-ACPA and (S)-Ethyl-ACPA were approximately an order of magnitude less potent
      at iGluR5 than at AMPA receptor subtypes, and neither compound showed detectable
      effects at iGluR6. The binding mode of (S)-Ethyl-ACPA at iGluR2 was examined by
      docking to the (S)-ACPA-iGluR2 complex.

PMID- 15236344
TI  - VCD configuration of enantiopure/-enriched tetrasubstituted alpha-fluoro
      cyclohexanones and their use for epoxidation of trans-olefins.
AB  - The configurations of three enantiopure tetrasubstituted alpha-fluoro
      cyclohexanones (-)-5Ia, (-)-5IIa and (-)-6a were determined by VCD and proved to
      be (-)-(2S,5R)-5Ia, (-)-(2R,5R)-5IIa, and (-)-(2R,5R)-6a. The VCD study also
      identified the conformers populated in CDCl3 solution, including higher-energy
      gas-phase conformers with equatorial fluorine for 5Ia and 5IIa that are
      stabilized in CDCl3 solution. Used as catalysts for epoxidation of trans olefins
      (beta-methylstyrene, stilbene, methyl p-methoxy cinnamate) by oxone, it was found
      that (-)-5Ia is the most efficient for all trans olefins (providing,
      respectively, 62%, 90% and 66% ee) but that all three ketones provide high ee%
      with stilbene (78-90% ee). Moreover, the configurations predicted from the stereo
      outcome of the epoxidation reaction are identical to those determined by VCD.

PMID- 15236345
TI  - Synthesis, enantiomeric resolution, and selective C-11 methylation of a highly
      selective radioligand for imaging the norepinephrine transporter with positron
      emission tomography.
AB  - Reboxetine, 2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, is a highly selective
      norepinephrine transporter (NET) blocker that has been used for the treatment of
      depression. Its methyl analogue, 2-[alpha-(2-methoxyphenoxy)benzyl]morpholine
      (MRB), has been radiolabeled with C-11 for studies of the NET system with
      positron emission tomography (PET). The normethyl precursor, 2-[alpha-(2
      hydroxyphenoxy)benzyl]morpholine (desethylreboxetine), was synthesized in 6%
      overall yield via a multi-step regio- and stereo-specific synthesis, starting
      from a mono-O-protected catechol. The resulting racemic mixture of
      desethylreboxetine was resolved by chiral HPLC to provide the (2S,3S) and (2R,3R)
      enantiomers in >98% enantiomeric excess. These enantiomers were then used as
      precursors for radiosynthesis to prepare enantiomerically pure individual 11C
      labeled MRB enantiomers for comparative PET studies in baboons. Selective C-11
      methylation at the phenolic oxygen with [11C]CH3I was achieved in the presence of
      excess base. After HPLC purification, racemic ((2S,3S)/(2R,3R)) or
      enantiomerically pure ((2S,3S) or (2R,3R)) [11C]MRB was obtained in 61-74% decay
      corrected radiochemical yields from [11C]CH3I in a synthesis time of 40 min with
      a radiochemical purity of >96% and a specific activity of 1.7-2.3 Ci/micromol (63
      85 GBq/micromol) corrected from the end of bombardment (EOB).

PMID- 15236346
TI  - Long-term depression in horizontal slices of the rat lateral amygdala.
AB  - Long-term depression (LTD) is an enduring decrease in synaptic efficacy and is
      thought to underlie memory. In contrast to investigations of plasticity
      mechanisms in the amygdala in rat coronal slices, this study was done in
      horizontal slices. Field excitatory postsynaptic potentials (fEPSPs) and EPSPs,
      respectively, were recorded extracellularly and intracellularly from the lateral
      nucleus of the amygdala (LA). We show that low-frequency stimulation (LFS)
      induces LTD in the LA, when stimulation electrodes were located in the LA. No
      significant differences were found between females and males. In dependence of
      strain variations, a reduction of GABAergic inhibition either reduced the
      magnitude of LTD or was a prerequisite for the induction of extracellularly
      recorded LA-LTD. Theta pulse stimulation (TPS) of afferents within the LA caused
      a weaker LTD than LFS. Theta burst stimulation (TBS) given 20 min after the end
      of LFS reversed LTD, whereas high-frequency stimulation (HFS) resulted in long
      term potentiation (LTP) that was significantly stronger than that obtained in
      naive slices. Therefore, primed induction of LTD facilitates high-frequency
      induced LTP in the rat lateral amygdala. NMDARs as well as group II mGluRs were
      involved in the mediation of LA-LTD. In contrast to data obtained by stimulation
      of afferents running within the LA, LFS of the external capsule fibers induced a
      weak LA-LTD, and TPS was not able to induce LTD. This study showed for the first
      time that LTD can be induced in the LA by standard LFS (900 pulses at 1 Hz) and
      that LTP stimuli reversed LTD. The results also provide further evidence for the
      broad sensitivity of synaptic plasticity mechanisms to the history of prior
      activity.

PMID- 15236347
TI  - The effect of N-ethylmaleimide on transmitter release from the skeletal
      neuromuscular junction of Bufo marinus.
AB  - N-ethylmaleimide (NEM) has been used extensively in biochemical assays as an
      inhibitor of the NEM sensitive fusion protein (NSF). However, examination of the
      effect of NEM on transmitter release in more physiologically relevant
      preparations has proved inconclusive. In the present study, we have examined the
      effect of low concentrations of NEM on synaptic transmission in intact nerve
      muscle preparations from toads (Bufo marinus). Under conditions of low
      transmitter release probability (0.3 mM calcium, 1 mM magnesium), treatment with
      NEM (10 microM) caused a significant increase in the amplitude of stimulus-evoked
      endplate potentials (EPPs) and a significant increase in the frequency of
      spontaneously occurring miniature EPPS (MEPPS) without affecting the amplitude of
      MEPPs. When the calcium concentration in the bath was raised to 4 mM, 10 microM
      NEM had no effect on EPP amplitude. Under these conditions, NEM treatment reduced
      paired pulse facilitation and increased depression during stimulus trains.
      Treatment with NEM also resulted in a significant decrease in the synaptic delay.
      The effects of NEM on transmitter release in the present study were not due to
      inactivation of G-proteins. The results of the present study show a calcium
      dependent facilitation of stimulus-evoked transmitter release by NEM. These
      results are discussed in terms of the possible sites of NEM action leading to the
      observed changes in transmitter release.

PMID- 15236348
TI  - Immunolocalization of CB1 receptor in rat striatal neurons: a confocal microscopy
      study.
AB  - Several lines of evidence indicate that cannabinoids, among other functions, are
      involved in motor control. Although cannabinoid receptors (CB(1)) mRNA has been
      observed in medium-sized spiny neurons of the striatum, a description of the
      precise localization of CB(1) at a protein level among striatal cells is still
      lacking. Therefore, we performed immunohistochemical studies with light and
      confocal microscopy to identify neuronal subpopulations that express CB(1) and to
      assess the distribution of the receptor within these neurons. In our single label
      light microscopy study, CB(1) was observed in most medium-sized neurons of the
      caudate-putamen. However, CB(1) was also present in large-sized neurons scattered
      throughout the striatum. Our dual-label study showed that 89.3% of projection
      neurons in matrix contain CB(1), and that 56.4% of projection neurons in patch
      are labeled for CB(1). To investigate the presence of CB(1) among the different
      subclasses of striatal interneurons we performed a double-labeling study matching
      CB(1) and each of the striatal interneuron markers, namely, choline acetyl
      transferase, parvalbumin, calretinin, and nitric oxide synthase. Our double-label
      study showed that most parvalbumin immunoreactive interneurons (86.5%), more than
      one-third (39.2%) of cholinergic interneurons, and about one-third (30.4%) of the
      NOS-positive neurons are labeled for CB(1). Calretinin-immunolabeled neurons were
      devoid of CB(1).

PMID- 15236349
TI  - Brain kinetics of methylphenidate (Ritalin) enantiomers after oral
      administration.
AB  - Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention
      deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the
      racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and
      microdialysis) in humans, baboons, and rats confirm the notion that
      pharmacological specificity of MP resides predominantly in the d-isomer. A recent
      report that intraperitoneally (i.p.) administered l-threo-MP displayed potent,
      dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats,
      raises the question of whether l-threo-MP has a similar effect when given orally.
      It has been speculated that l-threo-MP is poorly absorbed in humans when it is
      given orally because of rapid presystemic metabolism. To investigate whether l
      threo-MP or its metabolites can be delivered to the brain when it is given
      orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET
      studies were carried out in baboons and rats using orally delivered C-11-labeled
      d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In
      addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine
      stimulated locomotor activity in mice. There was a higher global uptake of carbon
      11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d
      threo-MP. Analysis of the chemical form of radioactivity in rat brain after
      [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo
      MP, it was mainly a labeled metabolite. The possibility that this labeled
      metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation,
      was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice
      at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the
      increased locomotor activity due to cocaine administration. These results suggest
      that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from
      the gastrointestinal tract and enters the brain after oral administration, but
      that l-threo-MP may not be pharmacologically active. These results are pertinent
      to the question of whether l-threo-MP contributes to the behavioral and side
      effect profile of MP during treatment of ADHD.

PMID- 15236350
TI  - Identification and characterization of a novel allosteric modulator (SoRI-6238)
      of the serotonin transporter.
AB  - In the present study we describe a novel agent, SoRI-6238 (ethyl 5-amino-3-(3,4
      dichlorophenyl)-1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamate) that partially
      inhibits 5-HT transporter (SERT) binding and allosterically modulates SERT
      function. Membranes were prepared from rat brain. SoRI-6238 partially inhibited
      SERT binding to brain membranes with a plateau at about 40% of control. SoRI-6238
      fully inhibited norepinephrine transporter (NET) and dopamine transporter (DAT)
      binding with IC(50) values of 12.1 microM and 5.8 microM, respectively. The
      apparent K(d) of [(125)I]RTI-55 binding to SERT increased, then reached a plateau
      with increasing concentrations of SoRI-6238. SoRI-6238 fully inhibited [(3)H]5-HT
      uptake, acting to decrease the V(max) (noncompetitive inhibition). In kinetic
      experiments, SoRI-6238 slowed the dissociation of [(125)I]RTI-55 from SERT and
      slowed the initial association rate. We conclude that SoRI-6238 partially
      inhibits SERT binding and function, most likely via an allosteric mechanism.

PMID- 15236351
TI  - 6-[18F]Fluoro-A-85380, a new PET tracer for the nicotinic acetylcholine receptor:
      studies in the human brain and in vivo demonstration of specific binding in white
      matter.

PMID- 15236353
TI  - Comparative analysis of two C-terminal kinesin motor proteins: KIFC1 and KIFC5A.
AB  - We have taken advantage of the close structural relationship between two C
      terminal motors, KIFC5A and KIFC1, to examine the sequence requirements for
      targeting of these two motors within the cell. Although KIFC5A and KIFC1 are
      almost identical in their motor and stalk domains, they differ in well-defined
      regions of their tail domains. Specific antisera to these motors were used to
      determine their localization to distinct subcellular compartments, the spindle
      for KIFC5A or membranous organelles for KIFC1. In addition to defining the
      intracellular localization of KIFC1, the reactivity of the KIFC1 antibody
      demonstrates that this motor contains a frame shift with respect to KIFC5A and is
      likely the product of a separate gene. The divergent tail domains of these motors
      are predicted to harbor specific information that directs them to their correct
      intracellular targets. In order to define the sequences responsible for the
      differential localization of these two motors, GFP was fused to motors with
      various tail deletions and their localization visualized after transfection. We
      were able to identify distinct sequences in each motor responsible for its unique
      cellular localization. The KIFC5A tail contains a 43 amino acid sequence with
      both nuclear localization and microtubule binding activity while KIFC1 contains a
      19 amino acid sequence sufficient to target this motor to membrane-bounded
      organelles.

PMID- 15236354
TI  - Actin filament binding by a monomeric IQGAP1 fragment with a single calponin
      homology domain.
AB  - IQGAP1 is a homodimeric protein that reversibly associates with F-actin,
      calmodulin, activated Cdc42 and Rac1, CLIP-170, beta-catenin, and E-cadherin. Its
      F-actin binding site includes a calponin homology domain (CHD) located near the N
      terminal of each subunit. Prior studies have implied that medium- to high
      affinity F-actin binding (5-50 microM K(d)) requires multiple CHDs located either
      on an individual polypeptide or on distinct subunits of a multimeric protein. For
      IQGAP1, a series of six tandem IQGAP coiled-coil repeats (IRs) located past the C
      terminal of the CHD of each subunit support protein dimerization and, by
      extension, the IRs or an undefined subset of them were thought to be essential
      for F-actin binding mediated by its CHDs. Here we describe efforts to determine
      the minimal region of IQGAP1 capable of binding F-actin. Several truncation
      mutants of IQGAP1, which contain progressive deletions of the IRs and CHD, were
      assayed for F-actin binding in vitro. Fragments that contain both the CHD and at
      least one IR could bind F-actin and, as expected, removal of all six IRs and the
      CHD abolished binding. Unexpectedly, a fragment called IQGAP1(2-210), which
      contains the CHD, but lacks IRs, could bind actin filaments. IQGAP1(2-210) was
      found to be monomeric, to bind F-actin with a K(d) of approximately 47 microM, to
      saturate F-actin at a molar ratio of one IQGAP1(2-210) per actin monomer, and to
      co-localize with cortical actin filaments when expressed by transfection in
      cultured cells. These collective results identify the first known example of high
      affinity actin filament binding mediated by a single CHD.

PMID- 15236355
TI  - Vinculin is proteolyzed by calpain during platelet aggregation: 95 kDa cleavage
      fragment associates with the platelet cytoskeleton.
AB  - The focal adhesion protein vinculin contributes to cell attachment and spreading
      through strengthening of mechanical interactions between cell cytoskeletal
      proteins and surface membrane glycoproteins. To investigate whether vinculin
      proteolysis plays a role in the influence vinculin exerts on the cytoskeleton, we
      studied the fate of vinculin in activated and aggregating platelets by Western
      blot analysis of the platelet lysate and the cytoskeletal fractions of
      differentially activated platelets. Vinculin was proteolyzed into at least three
      fragments (the major one being approximately 95 kDa) within 5 min of platelet
      activation with thrombin or calcium ionophore. The 95 kDa vinculin fragment
      shifted cellular compartments from the membrane skeletal fraction to the cortical
      cytoskeletal fraction of lysed platelets in a platelet aggregation-dependent
      manner. Vinculin cleavage was inhibited by calpeptin and E64d, indicating that
      the enzyme responsible for vinculin proteolysis is calpain. These calpain
      inhibitors also inhibited the translocation of full-length vinculin to the
      cytoskeleton. We conclude that cleavage of vinculin and association of vinculin
      cleavage fragment(s) with the platelet cytoskeleton is an activation response
      that may be important in the cytoskeletal remodeling of aggregating platelets.

PMID- 15236356
TI  - Curcumin inhibits cell motility and alters microfilament organization and
      function in prostate cancer cells.
AB  - Curcumin is a dietary phytochemical associated with anti-tumorigenic effects, but
      the mechanisms by which it inhibits cancer cell growth and metastasis are not
      completely understood. For example, little information is available regarding the
      effects of curcumin on cytoskeletal organization and function. In this study,
      time-lapse video and immunofluorescence labeling methods were used to demonstrate
      that curcumin significantly alters microfilament organization and cell motility
      in PC-3 and LNCaP human prostate cancer cells in vitro. Curcumin rapidly arrests
      cell movements and subsequently alters cell shape in the highly motile PC-3 cell
      line, but has a less noticeable effect on the relatively immobile LNCaP cell
      line. Stress fibers are augmented, and the overall quantity of f-actin appears to
      increase in both types of cells following curcumin treatment. Cytochalasin B (CB)
      disrupts microfilament organization in both cell lines, and causes vigorous
      membrane blebbing in PC-3 cells, but not LNCaP cells. Pre-treatment of cells with
      curcumin suppresses changes in microfilament organization caused by CB, and
      blocks PC-3 membrane blebbing. At least some of the effects of curcumin appear to
      be mediated by protein kinase C (PKC), as treatment with the PKC inhibitor
      bisindolylmaleimide inhibits the ability of curcumin to block CB-induced membrane
      blebbing. These findings demonstrate that curcumin exerts significant effects on
      the actin cytoskeleton in prostate cancer cells, including altering microfilament
      organization and function. This is a novel observation that may represent an
      important mechanism by which curcumin functions as a chemopreventative agent, and
      as an inhibitor of angiogenesis and metastasis.

PMID- 15236358
TI  - Dissociation of double-headed cytoplasmic dynein into single-headed species and
      its motile properties.
AB  - Cytoplasmic dynein is a minus-end directed microtubule motor and plays important
      roles in the transport of various intracellular cargoes. Cytoplasmic dynein
      comprises two identical heavy chains and forms a dimer (double-headed dynein);
      the total molecular weight of the cytoplasmic dynein complex is about 1.5
      million. The dynein motor domain is structurally very different from those of
      kinesin and myosin, and our understanding of the mechanisms of dynein energy
      transduction is limited mainly because of the difficulty in obtaining a
      sufficient quantity of purified and active cytoplasmic dynein. We purified
      cytoplasmic dynein, which was free from dynactin and other dynein-associated
      proteins. The purified cytoplasmic dynein was active in an in vitro motility
      assay. The controlled dialysis of the purified dynein against 4 M urea resulted
      in its complete dissociation into monomeric species (single-headed dynein). The
      separation of the dynein heads by the treatment was reversible. The MgATPase
      activities of the single-headed and reconstituted double-headed dynein were
      comparable to that of intact dynein. The double-headed dynein bundled
      microtubules in the absence of ATP; the single-headed dynein did not. The single
      headed dynein produced in vitro microtubule-gliding motility at velocities very
      similar to those of double-headed dynein at various ATP concentrations. These
      results indicate that a single cytoplasmic dynein heavy chain is sufficient to
      produce robust microtubule motility. Application of the double- and single-headed
      dynein molecules in various assay systems will elucidate the mechanism of action
      of the cytoplasmic dynein.

PMID- 15236357
TI  - Immunocytochemical localization of polyamines during attachment and spreading of
      retinal pigment epithelial and intestinal epithelial cells.
AB  - In order to form and maintain a protective barrier for photoreceptors, the
      retinal pigment epithelium relies on integrin signaling and related pathways to
      form adhesion complexes, undergo cell spreading, and establish a confluent
      cellular monolayer. Polyamines are multifunctional polycations that are essential
      for cell attachment and spreading, although their exact mechanisms of action are
      as yet unclear. We report new immunocytochemical evidence suggesting that in the
      cells of retinal pigment epithelium and also the intestinal epithelium,
      polyamines are present in a population of intracellular vesicles that appear
      transiently during initial stages of cell spreading. In newly attached cells with
      minimal spreading, the vesicles are seen near the nucleus, whereas in more highly
      spread cells, the vesicles are localized to the plasma membrane, near, but not
      precisely co-localized with an enzyme marker for adhesion complexes, focal
      adhesion kinase. We also observe pronounced nuclear staining in newly attached
      cells that have not spread, whereas this staining is decreased in cells that have
      spread. Nuclear staining has been previously reported in other cell types and has
      been attributed to DNA binding of polyamines, which is known to stabilize
      chromatin structure. We hypothesize that the appearance of polyamine vesicles
      near focal adhesions of cells undergoing attachment and spreading may reflect the
      mechanism by which polyamine pools are targeted to appropriate interaction sites
      necessary for the assembly of adhesion complexes. Alternatively, the vesicles
      could represent the mechanism by which polyamines are removed from the nucleus
      and possibly released from the cell.

PMID- 15236359
TI  - Diffusion measurements free of motion artifacts using intermolecular dipole
      dipole interactions.
AB  - Diffusion encoding, or diffusion weighting, is commonly achieved by applying a
      pair of balanced pulsed-field gradients during spin evolution. An alternative way
      to obtain diffusion measurements is to select dipolar correlation distances using
      the distant dipolar field (DDF) in systems with abundant spin density, such as
      water in tissues. Diffusion weighting using this effect is unique in that the
      refocusing "gradient" is carried within the sample, and thus the macroscopic
      motion of the sample is not expected to interfere with signal formation. The
      experiments presented here demonstrate that in moving phantoms, the phase shift
      of the signal due to linear motion is minimal in diffusion-weighted (DW) DDF
      measurements, and that motion artifacts in images of moving phantoms and the
      abdomen of live mice are small compared to standard pulsed-field-gradient
      methods. The technique may facilitate the use of DWI in typically motion-prone
      regions such as the abdomen, lungs, and heart.

PMID- 15236360
TI  - Feasibility and performance of breath-hold 3D true-FISP coronary MRA using self
      calibrating parallel acquisition.
AB  - Spatial resolution in 3D breath-hold coronary MR angiography (MRA) is limited by
      imaging time. The purpose of this work was to investigate the feasibility of
      improving the spatial resolution of coronary MRA using generalized
      autocalibrating partially parallel acquisition (GRAPPA) and fast imaging with
      steady state precession (True-FISP) data acquisition. Coronary data were acquired
      in 10 healthy volunteers. In five volunteers, the data were fully acquired in k
      space and decimated for GRAPPA with an outer reduction factor (ORF) of 2. The
      coil calibration in GRAPPA was improved by segmented least-squares fitting along
      the frequency-encoding direction. More than 5% of the total k-space lines were
      required for the calibration to achieve acceptable artifact suppression despite
      slightly lower signal-to-noise ratio (SNR). In another five volunteers, coronary
      data were obtained with both conventional and accelerated data acquisitions in
      the same imaging time. GRAPPA allowed a submillimeter in-plane resolution, and
      improved coronary artery definition with an acceptable loss of SNR. In
      conclusion, 3D breath-hold coronary MRA by GRAPPA and True-FISP is highly
      feasible.

PMID- 15236361
TI  - High temporal and spatial resolution 4D MRA using spiral data sampling and
      sliding window reconstruction.
AB  - Contrast-enhanced magnetic resonance angiography (CE-MRA) requires high spatial
      resolution to demonstrate detailed vasculature and high temporal resolution to
      capture the contrast bolus. Sparse bright voxels in MRA permit substantial
      undersampling in MRI data acquisition, allowing simultaneous high temporal and
      spatial resolution. We developed a time-resolved 3D MRA technique using the
      efficient spiral sampling trajectory, and performed off-resonance corrections
      using inhomogeneity field maps. View sharing and sliding window reconstruction
      were utilized to generate high temporal resolution. High-resolution 3D angiograms
      were generated at 1-2 s per frame, with a 5-8 ml gadolinium dose, in patients
      with vascular disease.

PMID- 15236362
TI  - Accelerating cardiac cine 3D imaging using k-t BLAST.
AB  - By exploiting spatiotemporal correlations in cardiac acquisitions using k-t
      BLAST, gated cine 3D acquisitions of the heart were accelerated by a net factor
      of 4.3, making single breathhold acquisitions possible. Sparse sampling of k-t
      space along a sheared grid pattern was implemented into a cine 3D SSFP sequence.
      The acquisition of low-resolution training data, which was required to resolve
      aliasing in the k-t BLAST method, was either interleaved into the sampling
      process or obtained in a separate prescan to allow for shorter breathhold
      durations in patients with heart disease. Volumetric datasets covering the heart
      with 20 slices at a spatial resolution of 2 x 2 x 5 mm3 were recorded with 20
      cardiac phases in a total breathhold duration of 25-27 sec, or 18 sec if partial
      Fourier sampling was additionally employed. The feasibility of the method was
      demonstrated on healthy volunteers and on patients. The comparison of endocardial
      area derived from single slices of the 3D dataset with values extracted from
      separate single-slice acquisitions showed no significant differences. By
      shortening the acquisition substantially, k-t BLAST may greatly facilitate
      volumetric imaging of the heart for evaluation of regional wall motion and the
      assessment of ventricular volume and ejection fraction.

PMID- 15236363
TI  - Ultrasound-guided MRI: preliminary results using a motion phantom.
AB  - In principal, both ultrasound (US) imaging and MRI can be performed
      simultaneously within the magnetic field of the scanner due to their different
      physical natures (i.e., sound waves vs. electromagnetic radiation). One potential
      application is to use US information for dynamic spatial organ localization to
      improve MR imaging, similar to MR navigator echoes. In this work, preliminary
      results are presented for US-guided MRI using position and orientation
      information extracted from US data to update the image slice position of an SSFP
      sequence in real time. Effective prospective motion compensation is shown for a
      phantom whose sinusoidal displacement can be fully corrected. Possible
      applications of simultaneous US-MRI acquisitions include real-time US-guided
      cardiac MRI or interventional procedures.

PMID- 15236364
TI  - NMR measurement of brain oxidative metabolism in monkeys using 13C-labeled
      glucose without a 13C radiofrequency channel.
AB  - We detected glutamate C4 and C3 labeling in the monkey brain during an infusion
      of [U-13C6]glucose, using a simple 1H PRESS sequence without 13C editing or
      decoupling. Point-resolved spectroscopy (PRESS) spectra revealed decreases in 12C
      bonded protons, and increases in 13C-bonded protons of glutamate. To take full
      advantage of the simultaneous detection of 12C- and 13C-bonded protons, we
      implemented a quantitation procedure to properly measure both glutamate C4 and C3
      enrichments. This procedure relies on LCModel analysis with a basis set to
      account for simultaneous signal changes of protons bound to 12C and 13C. Signal
      changes were mainly attributed to 12C- and 13C-bonded protons of glutamate. As a
      result, we were able to measure the tricarboxylic acid (TCA) cycle flux in a 3.9
      cm3 voxel centered in the monkey brain on a whole-body 3 Tesla system (VTCA =
      0.55 +/- 0.04 micromol x g(-1) x min(-1), N = 4). This work demonstrates that
      oxidative metabolism can be quantified in deep structures of the brain on
      clinical MRI systems, without the need for a 13C radiofrequency (RF) channel.

PMID- 15236365
TI  - Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of
      human knee articular cartilage: topographical variation and relationships to
      mechanical properties.
AB  - The macromolecular structure and mechanical properties of articular cartilage are
      interrelated and known to vary topographically in the human knee joint. To
      investigate the potential of delayed gadolinium-enhanced MRI of cartilage
      (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness
      cartilage disks were prepared from six anatomical locations in nonarthritic human
      knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were
      determined with the use of unconfined compression tests, followed by quantitative
      MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible,
      statistically significant differences in moduli between the patella and the
      medial/lateral femoral condyles. Typically, femoral cartilage showed higher
      Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage
      (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately
      reproduced the topographical variation in moduli. Additionally, T1, T2, and
      dGEMRIC revealed topographical differences that were not registered mechanically.
      The different MRI and mechanical parameters showed poor to excellent linear
      correlations, up to r = 0.87, at individual test sites. After all specimens were
      pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N =
      77). The results suggest that quantitative MRI can indirectly provide information
      on the mechanical properties of human knee articular cartilage, as well as the
      site-dependent variations of these properties. Investigators should consider the
      topographical variation in MRI parameters when conducting quantitative MRI of
      cartilage in vivo.

PMID- 15236366
TI  - BOLD response to direct thalamic stimulation reveals a functional connection
      between the medial thalamus and the anterior cingulate cortex in the rat.
AB  - Recent functional neuroimaging studies in humans and rodents have shown that the
      anterior cingulate cortex (ACC) is activated by painful stimuli, and plays an
      important role in the affective aspect of pain sensation. The aim of the present
      study was to develop a suitable stimulation method for direct activation of the
      brain in fMRI studies and to investigate the functional connectivity in the
      thalamo-cingulate pathway. In the first part of the study, tungsten, stainless
      steel, or glass-coated carbon fiber microelectrodes were implanted in the left
      medial thalamus (MT) of anesthetized rats, and T2*-weighted gradient-echo (GE)
      images were obtained in the sagittal plane on a 4.7 T system (Biospec BMT 47/40).
      Only the images obtained with the carbon fiber electrode were acceptable without
      a reduction of the signal-to-noise ratio (SNR) and image distortion. In the
      second part of the study, a series of two-slice GE images were acquired during
      electrical stimulation of the MT with the use of a carbon fiber electrode. A
      cross-correlation analysis showed that the signal intensities of activated areas
      in the ipsilateral ACC were significantly increased by about 4.5% during MT
      stimulation. Functional activation, as assessed by the distribution of c-Fos
      immunoreactivity, showed strong c-Fos expression in neurons in the ipsilateral
      ACC. The present study shows that glass-coated carbon fiber electrodes are
      suitable for fMRI studies and can be used to investigate functional
      thalamocortical activation.

PMID- 15236367
TI  - Evaluation of renal parenchymal disease in a rat model with magnetic resonance
      elastography.
AB  - Alterations in the mechanical properties or "hardness" of tissues allow
      physicians to detect disease by palpation. Recently, attempts have been made to
      quantitate and image these tissue properties with the use of magnetic resonance
      elastography (MRE). This technique has been validated in ex vivo specimens,
      including kidney, breast, and prostate. In this study, in vivo MRE imaging of rat
      renal cortex is demonstrated and validated with a disease model that will
      facilitate further studies. Normal rats and rats with nephrocalcinosis induced
      with either 2 or 4 weeks of ethylene glycol exposure were studied with MRE.
      Histology in the diseased rats documented the presence of nephrocalcinosis. MRE
      measurements and images of shear stiffness were highly reproducible in individual
      rats. The shear stiffness of the renal cortex in normal rats was 3.87 kPa (95% CI
      2.84-4.90 kPa). The shear stiffness increased to 5.02 kPa (95% CI 3.34-6.70 kPa)
      after 2 weeks of exposure, and to 6.49 kPa (95% CI 4.84-8.14 kPa) after 4 weeks
      of exposure (P = 0.0302, alpha < 0.05). MRE is capable of detecting alterations
      in the tissue mechanical properties of kidneys in vivo. It is a promising
      noninvasive technique that might have pathologic and prognostic significance.

PMID- 15236368
TI  - Determination of regional VA/Q by hyperpolarized 3He MRI.
AB  - Alveolar ventilation/perfusion ratio (VA/Q) is a key parameter in functional
      imaging of the lung. Herein, regional VA/Q was calculated from regional values of
      alveolar partial pressure of oxygen (PAO2) measured by hyperpolarized 3He gas MRI
      (HP 3He MRI). Yorkshire pigs (n = 7, mean weight = 25 kg) were paralyzed and
      maintained under isoflurane anesthesia. Animals were placed into a birdcage coil,
      then transferred to the bore of a 1.5 T MRI unit. Prior to imaging, animals were
      manually ventilated with room air for 5 min, then a 3He gas mixture was
      administered during breathhold and imaging performed. PAO2 was measured based on
      the decay rate of 3He signal. Subjects' blood gas concentrations were measured
      and these values and PAO2 values entered into a system of four equations with
      four unknowns. Calculated VA/Q values were analyzed by preparing frequency
      distributions for the entire lung and compared to VA/Q frequency distributions
      previously established in the literature as normal using other diagnostic
      techniques. Distributions were consistent with those in the literature,
      indicating that HP 3He MRI may be an accurate, quantitative, noninvasive, and
      nonradioactive method for acquiring VA/Q for small regions of the lung.

PMID- 15236369
TI  - In vivo cellular imaging of magnetically labeled hybridomas in the spleen with a
      1.5-T clinical MRI system.
AB  - The feasibility of in vivo cellular imaging using a 1.5 T clinical magnet was
      studied in the mouse. Hybridoma cells were labeled with anionic gamma-Fe2O3
      superparamagnetic iron oxide nanoparticles. These were internalized by the
      endocytose pathway. Both electron spin resonance and magnetophoresis as a measure
      of the labeled cells migration velocity under a magnetic field were used to
      quantify particle uptake. A fast (< 2 hr) and substantial (up to 5 pg of iron per
      cell) internalization of nanoparticles by hybridomas was found, with good
      agreement between the two methods used. Hybridomas labeled with 2.5 pg iron per
      cell were injected intraperitoneally to male Swiss nude mice. A decrease in the
      spleen signal, suggesting a "homing" of labeled hybridomas to this organ, was
      found 24 hr later by MRI performed at 1.5 T. Furthermore, in labeled cells
      recovered from the spleen by ex vivo magnetic sorting, a mean of 0.5 pg iron per
      cell was found, i.e., a value five times lower than that of the injected
      hybridomas. This finding is consistent with in vivo proliferation of these cells.
      In addition, the amount of labeled hybridomas present in the spleen was found to
      correlate with MRI signal intensity.

PMID- 15236370
TI  - Fast acquisition-weighted three-dimensional proton MR spectroscopic imaging of
      the human prostate.
AB  - The clinical application of 3D proton spectroscopic imaging (3D SI) of the human
      prostate requires a robust suppression of periprostatic lipid signal
      contamination, minimal intervoxel signal contamination, and the shortest possible
      measurement time. In this work, a weighted elliptical sampling of k-space,
      combined with k-space filtering and pulse repetition time (TR) reduction
      minimized lipid signals, intervoxel contamination, and measurement time. At 1.5
      T, the MR-visible prostate metabolites citrate, creatine, and choline can now be
      mapped over the entire human prostate with uncontaminated spherical voxels, with
      a volume down to 0.37 cm3, in measurement times of 7-15 min.

PMID- 15236371
TI  - Functional MRI of the rodent somatosensory pathway using multislice echo planar
      imaging.
AB  - A multislice EPI sequence was used to obtain functional MR images of the entire
      rat brain with BOLD contrast at 11.7 T. Ten to 11 slices covering the rat brain,
      with an in-plane resolution of 300 microm, provided enough sensitivity to detect
      activation in brain regions known to be involved in the somatosensory pathway
      during stimulation of the forelimbs. These regions were identified by warping a
      digitized rat brain atlas to each set of images. Data analysis was constrained to
      four major areas of the somatosensory pathway: primary and secondary
      somatosensory cortices, thalamus, and cerebellum. Incidence maps were generated.
      Electrical stimulation at 3 Hz led to significant activation in the primary
      sensory cortex in all rats. Activation in the secondary sensory cortex and
      cerebellum was observed in 70% of the studies, while thalamic activation was
      observed in 40%. The amplitude of activation was measured for each area, and
      average response time courses were calculated. Finally, the frequency dependence
      of the response to forepaw stimulation was measured in each of the activated
      areas. Optimal activation occurred in all areas at 3 Hz. These results
      demonstrate that whole-brain fMRI can be performed on rodents at 11.7 T to probe
      a well-defined neural network.

PMID- 15236372
TI  - 500-element ultrasound phased array system for noninvasive focal surgery of the
      brain: a preliminary rabbit study with ex vivo human skulls.
AB  - The aim of this study was to test a prototype MRI-compatible focused ultrasound
      phased array system for trans-skull brain tissue ablation. Rabbit thigh muscle
      and brain were sonicated with a prototype, hemispherical 500-element ultrasound
      phased array operating at frequencies of 700-800 kHz. An ex vivo human skull
      sample was placed between the array and the animal tissue. The temperature
      elevation during 20-30-sec sonications was monitored using MRI thermometry. The
      induced focal lesions were observed in T2 and contrast-enhanced T1-weighted fast
      spin echo images. Whole brain histology evaluation was performed after the
      sonications. The results showed that sharp temperature elevations can be produced
      both in the thigh muscle and in the brain. High-power sonications (600-1080 W)
      produced peak temperatures up to 55 degrees C and focal lesions that were
      consistent with thermal tissue damage. The lesion size was found to increase with
      increasing peak temperature. The device was then modified to operate in the
      orientation that will be used in the clinic and successfully tested in phantom
      experiments. As a conclusion, this study demonstrates that it is possible to
      create ultrasound-induced lesions in vivo through a human skull under MRI
      guidance with this large-scale phased array.

PMID- 15236374
TI  - Use of spherical harmonic deconvolution methods to compensate for nonlinear
      gradient effects on MRI images.
AB  - Spatial encoding in MR techniques is achieved by sampling the signal as a
      function of time in the presence of a magnetic field gradient. The gradients are
      assumed to generate a linear magnetic field gradient, and typical image
      reconstruction relies upon this approximation. However, high-speed gradients in
      the current generation of MRI scanners often sacrifice linearity for improvements
      in speed. Such nonlinearity results in distorted images. The problem is presented
      in terms of first principles, and a correction method based on a gradient field
      spherical harmonic expansion is proposed. In our case, the amount of distortion
      measured within a typical field of view (FOV) required for head imaging is
      sufficiently large that without the use of some distortion correction technique,
      the images would be of limited use for stereotaxy or longitudinal studies, where
      precise volumetric information is required.

PMID- 15236373
TI  - Opiate tolerance by heroin self-administration: an fMRI study in rat.
AB  - Functional MRI (fMRI) was employed to determine whether repeated heroin self
      administration (SA) produces tolerance or sensitization in the brain of heroin-SA
      rats. Twelve rats were evenly divided into saline and heroin (0.06 mg/kg, 4
      hr/day) SA groups. There was a progressive increase in drug-SA behavior and daily
      heroin intake during the 8-9 days of heroin-SA training. Within 24 hr after the
      last session of daily SA, acute heroin (0.1 mg/kg) administration induced
      regional blood oxygen level-dependent (BOLD) signals in both groups of rats. The
      positive BOLD signals appeared mainly in the cortical regions, including the
      prefrontal cortex, cingulate, and olfactory cortex, while the negative BOLD
      signals were predominantly located in subcortical regions such as caudate and
      putamen, nucleus accumbens, thalamus, and hypothalamus. However, the number of
      activated voxels or BOLD-signal intensity was significantly less in heroin-SA rat
      in regions of prefrontal cortex, nucleus accumbens, and thalamus, etc., compared
      to the changes in the saline control rats. Application of gamma-vinyl GABA (100
      mg/kg), an irreversible GABA-transaminase inhibitor, failed to block opiate
      actions in the heroin-SA rats. Together, these data suggest that repeated heroin
      SA produces tolerance or desensitization of opiate actions in the rat brain,
      which may in turn potentiate drug SA behavior and drug intake.

PMID- 15236375
TI  - Signal-to-noise ratio behavior of steady-state free precession.
AB  - Steady-state free precession (SSFP) is a rapid gradient-echo imaging technique
      that has recently gained popularity and is used in a variety of applications,
      including cardiac and real-time imaging, because of its high signal and favorable
      contrast between blood and myocardium. The purpose of this work was to examine
      the signal-to-noise ratio (SNR) behavior of images acquired with SSFP, and the
      dependence of SNR on imaging parameters such as TR, bandwidth, and image
      resolution, and the use of multi-echo sequences. In this work it is shown that
      the SNR of SSFP sequences is dependent only on pulse sequence efficiency, voxel
      dimensions, and relaxation parameters (T1 and T2). Notably, SNR is insensitive to
      bandwidth unless increases in bandwidth significantly decrease efficiency.
      Finally, we examined the relationship between pulse sequence performance (TR and
      efficiency) and gradient performance (maximum gradient strength and slew rate)
      for several imaging scenarios, including multi-echo sequences, to determine the
      optimum matching of maximum gradient strength and slew rate for gradient hardware
      designs. For standard modern gradient hardware (40 mT/m and 150 mT/m/ms), we
      found that the maximum gradient strength is more than adequate for the imaging
      resolution that is commonly encountered with rapid scouting (3 mm x 4 mm x 10 mm
      voxel). It is well matched for typical CINE and real-time cardiac imaging
      applications (1.5 mm x 2 mm x 6 mm voxel), and is inadequate for optimal matching
      with slew rate for high-resolution applications such as musculoskeletal imaging
      (0.5 x 0.8 x 3 mm voxel). For the lower-resolution methods, efficiency could be
      improved with higher slew rates; this provokes interest in designing methods for
      limiting dB/dt peripherally while achieving high switching rates in the imaging
      field of view. The use of multi-echo SSFP acquisitions leads to substantial
      improvements in sequence performance (i.e., increased efficiency and shorter TR).

PMID- 15236376
TI  - Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.
AB  - A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI
      techniques have been demonstrated in recent years. One of the reasons these
      methods are still not routinely used is the limited extent of the imaging region.
      Of the ASL methods proposed to date, continuous ASL (CASL) with a separate
      labeling coil is particularly attractive for whole-brain studies at high fields.
      This approach can provide an increased signal-to-noise ratio (SNR) in perfusion
      images because there are no magnetization transfer (MT) effects, and lessen
      concerns regarding RF power deposition at high field because it uses a local
      labeling coil. In this work, we demonstrate CASL whole-brain quantitative
      perfusion imaging at 3.0 T using a combination of strategies: 3D volume
      acquisition, background tissue signal suppression, and a separate labeling coil.
      The results show that this approach can be used to acquire perfusion images in
      all brain regions with good sensitivity. Further, it is shown that the method can
      be performed safely on humans without exceeding the current RF power deposition
      limits. The current method can be extended to higher fields, and further improved
      by the use of multiple receiver coils and parallel imaging techniques to reduce
      scan time or provide increased resolution.

PMID- 15236377
TI  - Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of
      the heart.
AB  - A novel pulse sequence scheme is presented that allows the measurement and
      mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath
      hold. Two major modifications of conventional Look-Locker (LL) imaging are
      introduced: 1) selective data acquisition, and 2) merging of data from multiple
      LL experiments into one data set. Each modified LL inversion recovery (MOLLI)
      study consisted of three successive LL inversion recovery (IR) experiments with
      different inversion times. We acquired images in late diastole using a single
      shot steady-state free-precession (SSFP) technique, combined with sensitivity
      encoding to achieve a data acquisition window of < 200 ms duration. We calculated
      T1 using signal intensities from regions of interest and pixel by pixel. T1
      accuracy at different heart rates derived from simulated ECG signals was tested
      in phantoms. T1 estimates showed small systematic error for T1 values from 191 to
      1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one
      patient with acute myocardial infarction before and after administration of Gd
      DTPA. T1 values for myocardium and noncardiac structures were in good agreement
      with values available from the literature. The region of infarction was clearly
      visualized. MOLLI provides high-resolution T1 maps of human myocardium in native
      and post-contrast situations within a single breath-hold.

PMID- 15236378
TI  - Design of symmetric-sweep spectral-spatial RF pulses for spectral editing.
AB  - Spectral-spatial RF (SSRF) pulses allow simultaneous selection in both frequency
      and spatial domains. These pulses are particularly important for clinical and
      research MR spectroscopy (MRS) applications for suppression of large water and
      lipid resonances. Also, the high bandwidth of the subpulses (5-10 kHz) greatly
      reduces the spatial-shift errors associated with different chemical shifts.
      However, the use of high-bandwidth subpulses along with enough spectral bandwidth
      to measure a typical range of metabolite frequencies (e.g., 300 Hz at 3 T) can
      require RF amplitudes beyond the limits of the RF amplifier of a typical scanner.
      In this article, a new method is described for designing nonlinear-phase 180
      degrees SSRF pulses that can be used for spectral editing. The novel feature of
      the pulses is that the spectral profile develops as a symmetric sweep, from the
      outside edges of the spectral window towards the middle, so that coupled
      components are tipped simultaneously and over a short interval. Pulses were
      designed for lactate editing at 1.5 T and 3 T. The spectral and spatial spin-echo
      profiles of the new pulses were measured experimentally. Spectra acquired in
      phantom experiments showed a well-resolved, edited lactate doublet, with 91% to
      93% editing efficiency.

PMID- 15236379
TI  - Quantification of the curvature and shape of the interventricular septum.
AB  - The interventricular septum (IVS) occupies a unique position within the heart,
      lying between the left (LV) and right (RV) ventricular cavities. Changes in its
      normal geometry may signify not only abnormalities of the septal myocardium, but
      also abnormal pressure differences between the LV and RV. Flattening of the IVS
      has been noted with cross-sectional imaging in association with pulmonary
      hypertension, but the septal curvature and shape have not previously been
      measured in three dimensions. This paper describes a method to model the RV
      surface of the IVS from spatially registered cross-sectional images for
      measurements of curvature. A smoothing 2D spline surface is constructed through
      the RV septal surface at regular times during the cardiac cycle, and the
      principal curvatures, as well as the Gaussian and mean curvatures, shape index,
      and curvedness, are calculated. Vector and color surface maps and graphs of
      average curvature and shape indices are constructed. Consistent curvature
      patterns were observed in four normal subjects. This method of measuring septal
      geometry can provide potentially useful new information on the effects of RV
      disease. We examine the problem of describing septal motion, and describe a
      simple measure of septal curvature that may be of clinical value.

PMID- 15236380
TI  - Localized 7Li MR spectroscopy and spin relaxation in rat brain in vivo.
AB  - Localized 7Li MR point-resolved spectroscopy (PRESS) was developed as a technique
      to measure lithium (Li) concentration in rat brain in vivo. Localized 7Li spectra
      could be obtained at 4.7 T in a 0.7-ml voxel in rat brain over the entire
      therapeutic range of serum Li for humans. Localized 7Li spin-lattice (T1) and
      spin-spin (T2) relaxation times were measured. Measured intensities were
      corrected for spin relaxation effects and 7Li MR visibility in vivo. The average
      T1 was 3.3 +/- 0.9 sec, and the average T2 was 82 +/- 20 ms. Neither T1 nor T2
      correlated with brain concentration. No statistically significant change was
      found in either T1 or T2 from approximately 7-17 days of Li dosing.

PMID- 15236382
TI  - Contrast-enhanced dental MRI for visualization of the teeth and jaw.
AB  - A technique for contrast-enhanced dental MRI is described that enables 3D
      visualization of the oral cavity, including the jaw and teeth. Since teeth are MR
      invisible, the basic principle of this technique is that the teeth and jaw can be
      observed indirectly through contrast with a surrounding MR-visible medium. For
      this purpose, the oral cavity is filled with a nontoxic substance, such as water
      or MR contrast media, that gives a high MR signal. A 3D data set covering the
      entire buccal space is acquired, and the image intensities are inverted. Since
      isosurface reconstructions of the teeth and jaw, as well as panoramic views
      analogous to orthopantomography, can be extracted from these data, contrast
      enhanced dental MRI may be useful as a flexible tool for dentistry and
      orthodontics. Moreover, contrast-enhanced dental MRI works without radiation
      exposure, and therefore it is an interesting alternative to X-ray-based imaging
      modalities such as conventional radiography and dental CT. In this article, some
      preliminary results obtained with contrast-enhanced dental MRI are shown in order
      to demonstrate the feasibility and performance of this new approach.

PMID- 15236381
TI  - In vivo 5-fluorouracil and fluoronucleotide T1 relaxation time measurements using
      the variable nutation angle method.
AB  - 19Fluorine NMRS has the potential to enable noninvasive predictions of tumor
      response to 5-fluorouracil (5FU) therapy based on tumor pharmacokinetics.
      Knowledge of the T1's of 5FU and its fluoronucleotide anabolites (FNuc) is
      required for quantitative spectral analysis and selection of optimal pulse
      parameters. We used the variable nutation angle (VNA) method to determine T1's of
      5FU and FNuc in subcutaneous Walker 256 rat mammary carcinosarcoma tumors
      transfected with a cytosine deaminase/uracil phosphoribosyltransferase fusion
      gene. We calibrated in vivo NAs using methoxydifluoroacetate to ensure the
      accuracy of these measurements. The T1's were calculated based on signal
      intensities acquired with NAs of 20 degrees, 35 degrees, 45 degrees, 60 degrees,
      and 75 degrees. The acquisition order of these NAs was shuffled to reduce the
      effect of signal variations. The determined T1's for 5FU and FNuc (2.3 +/- 0.1 s
      and 1.3 +/- 0.1 s, respectively) represent the first reported in vivo
      measurements for these metabolites in tumor.

PMID- 15236383
TI  - MRI measurement of liver regeneration in mice following partial hepatectomy.
AB  - Improvements in noninvasive imaging modalities are crucial for preoperative in
      vivo assessments of liver condition and potential for regeneration after liver
      resection for removal of liver tumors. To that end, an MRI study of liver
      regeneration in mice following partial hepatectomy is described and validated.
      Hepatic volumes were accurately measured from contrast-enhanced, gradient-echo
      images of the liver. Regeneration curves were constructed for a series of mice (N
      = 6) from a longitudinal MR study, with images collected 1, 2, 3, 4, 5, and 9
      days following surgery. We validated the MR method by correlating serial MR
      measured volumes with liver wet weight. The success of this method will enable
      future studies to better elucidate the factors that affect regeneration, and help
      to optimize the timing and dosing of chemotherapeutics to minimize their
      deleterious effects on liver regeneration.

PMID- 15236384
TI  - Correction for gradient nonlinearity in continuously moving table MR imaging.
AB  - Recently, a number of methods have been demonstrated for large field of view MR
      imaging using continuous table motion. As with conventional, fixed-table MRI, the
      spatial encoding is performed using magnetic field gradients. However, it is
      demonstrated in this work that as a consequence of every measurement being made
      at a slightly different displacement between the object and the gradient field,
      gradient nonlinearities are manifest as blurring in addition to spatial
      distortion. Moreover, the blurring is spatially dependent. It is also shown that
      correcting all phase-encoding steps individually or in groups can reduce these
      effects. Phantom and in vivo results are shown which demonstrate the
      effectiveness of the correction.

PMID- 15236385
TI  - Increasing the signal-to-noise ratio in DENSE MRI by combining displacement
      encoded echoes.
AB  - A new technique was developed to increase the signal-to-noise ratio (SNR) in
      displacement encoding with stimulated echoes (DENSE) MRI. This signal-averaged
      DENSE (sav-DENSE) technique is based on the SNR advantage of extracting a pair of
      DENSE images with uncorrelated noise from the complex complementary spatial
      modulation of the magnetization image, and combining them during image
      reconstruction. Eleven healthy volunteers were imaged at three short-axis
      locations with the use of sav-DENSE, cine DENSE, and myocardial tagging pulse
      sequences. In this study, sav-DENSE increased the SNR by 15-34% as compared to
      cine DENSE. Circumferential strain values measured by sav-DENSE and myocardial
      tagging were strongly correlated (slope = 0.95, intercept = -0.02, R = 0.92) and
      within the 95% limits of agreement. The breath-hold sav-DENSE technique yielded
      relatively accurate and precise quantification of 2D intramyocardial function,
      with a 40.2-ms temporal resolution and a 3.5 x 3.5 mm2 spatial resolution.

PMID- 15236386
TI  - Fourier components of inhomogeneously broadened water resonances in breast: a new
      source of MRI contrast.
AB  - High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using
      echo-planar spectroscopic imaging from patients with suspicious breast lesions.
      The water resonances in small voxels are inhomogenously broadened and often have
      distinct components. Images were calculated with intensity proportional to the
      Fourier components of the water resonance in each voxel at different offsets from
      the peak frequency. The results demonstrate that in breast the off-peak Fourier
      component images of water are qualitatively different from those derived from the
      peak height of the water resonance. These differences most likely reflect
      underlying anatomy or physiology. In conventional images, the superposition of
      the various Fourier components of the water signal may cause loss of detail. The
      synthesis of water Fourier component images from high spectral and spatial
      resolution data may provide a new form of contrast, and increase sensitivity to
      subvoxel physiology and anatomy.

PMID- 15236387
TI  - Fast isotropic volumetric coronary MR angiography using free-breathing 3D radial
      balanced FFE acquisition.
AB  - A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is
      the time-consuming examination necessitated by extensive scout scanning and
      precise slice planning. To improve ease of use and cover larger parts of the
      anatomy, it appears desirable to image the entire heart with high spatial
      resolution instead. For this purpose, an isotropic 3D-radial acquisition was
      employed in this study. This method allows undersampling of k-space in all three
      spatial dimensions, and its insensitivity to motion enables extended acquisitions
      per cardiac cycle. We present initial phantom and in vivo results obtained in
      volunteers that demonstrate large volume coverage with high isotropic spatial
      resolution. We were able to visualize all major parts of the coronary arteries
      retrospectively from the volume data set without compromising the image quality.
      The scan time ranged from 10 to 14 min during free breathing at a heart rate of
      60 bpm, which is comparable to that of a thin-slab protocol comprising multiple
      scans for each coronary artery.

PMID- 15236388
TI  - High-resolution multistation peripheral MR angiography using undersampled
      projection reconstruction imaging.
AB  - A novel protocol for three-station MR angiography (MRA) of the lower extremities
      is described. A time-resolved undersampled projection reconstruction (PR)
      acquisition was used to image the calf station during a first injection, and non
      time-resolved PR acquisitions were used with the bolus-chase technique to image
      the abdomen and thigh stations during a second injection. The streak artifacts
      resulting from undersampling the PR data were reduced with the use of a spatial
      Fermi filter based on the sensitivity of each coil element in a peripheral
      vascular phased-array coil. This novel technique provided high spatial resolution
      and a broad range of coverage, and depicted the contrast dynamics in the most
      distal station of the lower extremities.

PMID- 15236389
TI  - Deconvolution of dynamic contrast-enhanced MRI data by linear inversion: choice
      of the regularization parameter.
AB  - Truncated singular value decomposition (TSVD) is an effective method for the
      deconvolution of dynamic contrast-enhanced MRI. Two robust methods for the
      selection of the truncation threshold on a pixel-by-pixel basis--generalized
      cross validation (GCV) and the L-curve criterion (LCC)--were optimized and
      compared to paradigms in the literature. The methods lead to improvements in the
      estimate of the residue function and of its maximum and converge properly with
      SNR. The oscillations typically observed in the solution vanish entirely and
      perfusion is more accurately estimated at small mean transit times. This results
      in improved image contrast and increased sensitivity to perfusion abnormalities,
      at the cost of 1-2 min in calculation time and isolated instabilities in the
      image. It is argued that the latter problem may be resolved by optimization.
      Simulated results for GCV and LCC are equivalent in terms of performance, but GCV
      is faster.

PMID- 15236390
TI  - MR coil design for simultaneous tip tracking and curvature delineation of a
      catheter.
AB  - In active catheter tracking, small RF coils are attached to the catheter for
      localization. For interactive catheter steering at vessel branchings, it is
      necessary to visualize not only a single point near the catheter tip but also the
      entire shape and orientation of the catheter's distal end. Therefore, a 35-mm
      long twisted-pair RF coil was added to a 5 French intravascular catheter with a
      single tip-tracking coil. With the use of small nonmagnetic electronic components
      at the catheter tip, and a special switching circuitry outside the catheter, the
      coil assembly could be operated in two different modes. During MRI, the tip
      tracking coil was detuned so that the MR signal was received by the visualization
      coil only. During tracking, detuning was switched off and the MR signal was
      predominantly received by the more sensitive tracking coil. The catheter was used
      in combination with a MR pulse sequence with automatic slice positioning so that
      the current imaging slice was always placed at the position of the catheter tip.
      Phantom and animal experiments showed that the catheter tip is better visualized
      with the combined approach than with a tracking coil alone.

PMID- 15236393
TI  - Message from the editor.

PMID- 15236395
TI  - Therapeutics in cognitive and behavioral neurology.

PMID- 15236396
TI  - Doing more with less: the plight of the failing hippocampus.

PMID- 15236397
TI  - Human T-lymphotropic virus type II and neurological disease.
AB  - Human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II) are closely
      related retroviruses with similar biological properties and common modes of
      transmission. HTLV-I infection is endemic in well-defined geographic regions, and
      it is estimated that some 20 million individuals are infected worldwide. Although
      most infected individuals are asymptomatic carriers, some 2 to 5% will develop a
      chronic encephalomyelopathy, HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). In contrast with HTLV-I, the role of HTLV-II in the
      development of neurological disorders is much less clear. HTLV-II is endemic in
      many native Amerindian groups and epidemic in injecting drug users (IDUs)
      worldwide. To evaluate the role of HTLV-II in neurological disease, we have
      critically reviewed all reported cases of HTLV-II-associated disorders. This has
      confirmed that although rare infection is associated with a disorder clinically
      similar or identical to HAM/TSP. However, most reports that have attributed
      infection to a range of other neurological disorders are difficult to evaluate in
      that in many cases either the association appears to be fortuitous or the
      presentations were confounded by a background of concomitant human
      immunodeficiency virus-1 infection and/or active IDU. In view of the many HTLV-II
      infected individuals in urban areas of North America and Europe, neurologists
      should be aware of the potential clinical consequences of this infection.

PMID- 15236398
TI  - Levodopa: faster and better word learning in normal humans.
AB  - Dopamine is a potent modulator of learning and has been implicated in the
      encoding of stimulus salience. Repetition, however, as required for the
      acquisition and reacquisition of sensorimotor or cognitive skills (e.g., in
      aphasia therapy), decreases salience. We here tested whether increasing brain
      levels of dopamine during repetitive training improves learning success. Forty
      healthy humans took 100mg of the dopamine precursor levodopa or placebo daily for
      5 days in a randomized double-blind and parallel-group design. Ninety minutes
      later on each day, subjects were trained on an artificial vocabulary using a high
      frequency repetitive approach. Levodopa significantly enhanced the speed, overall
      success, and long-term retention of novel word learning in a dose-dependent
      manner. These findings indicate new ways to potentiate learning in a variety of
      domains if conventional training alone fails.

PMID- 15236400
TI  - Diffuse axonal injury in children: clinical correlation with hemorrhagic lesions.
AB  - An inception cohort of 40 children and adolescents with traumatic brain injury
      and suspected diffuse axonal injury were studied using a new high-resolution
      magnetic resonance imaging susceptibility-weighted technique that is very
      sensitive for hemorrhage. A blinded comparison was performed between the extent
      of parenchymal hemorrhage and initial clinical variables as well as outcomes
      measured at 6 to 12 months after injury. Children with lower Glasgow Coma Scale
      scores (< or =8, n = 30) or prolonged coma (>4 days, n = 20) had a greater
      average number (p = 0.007) and volume (p = 0.008) of hemorrhagic lesions.
      Children with normal outcomes or mild disability (n = 30) at 6 to 12 months had,
      on average, fewer hemorrhagic lesions (p = 0.003) and lower volume (p = 0.003) of
      lesions than those who were moderately or severely disabled or in a vegetative
      state. Significant differences also were observed when comparing regional injury
      to clinical variables. Because susceptibility-weighted imaging is much more
      sensitive than conventional T2*-weighted gradient-echo sequences in detecting
      hemorrhagic diffuse axonal injury, more accurate and objective assessment of
      injury can be obtained early after insult, and may provide better prognostic
      information regarding duration of coma as well as long-term outcome.

PMID- 15236399
TI  - Medial temporal lobe function and structure in mild cognitive impairment.
AB  - Functional magnetic resonance imaging (fMRI) was used to study memory-associated
      activation of medial temporal lobe (MTL) regions in 32 nondemented elderly
      individuals with mild cognitive impairment (MCI). Subjects performed a visual
      encoding task during fMRI scanning and were tested for recognition of stimuli
      afterward. MTL regions of interest were identified from each individual's
      structural MRI, and activation was quantified within each region. Greater extent
      of activation within the hippocampal formation and parahippocampal gyrus (PHG)
      was correlated with better memory performance. There was, however, a paradoxical
      relationship between extent of activation and clinical status at both baseline
      and follow-up evaluations. Subjects with greater clinical impairment, based on
      the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right
      PHG during encoding, even after accounting for atrophy. Moreover, those who
      subsequently declined over the 2.5 years of clinical follow-up (44% of the
      subjects) activated a significantly greater extent of the right PHG during
      encoding, despite equivalent memory performance. We hypothesize that increased
      activation in MTL regions reflects a compensatory response to accumulating AD
      pathology and may serve as a marker for impending clinical decline.

PMID- 15236401
TI  - L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impairs
      mitochondrial respiration and damages dopaminergic neurons as seen in Parkinson's
      disease (PD). Here, we report that L-3-hydroxyacyl-CoA dehydrogenase type
      II/amyloid binding alcohol dehydrogenase (HADH II/ABAD), a mitochondrial
      oxidoreductase enzyme involved in neuronal survival, is downregulated in PD
      patients and in MPTP-intoxicated mice. We also show that transgenic mice with
      increased expression of human HADH II/ABAD are significantly more resistant to
      MPTP than their wild-type littermates. This effect appears to be mediated by
      overexpression of HADH II/ABAD mitigating MPTP-induced impairment of oxidative
      phosphorylation and ATP production. This study demonstrates that HADH II/ABAD
      modulates MPTP neurotoxicity and suggests that HADH II/ABAD mimetics may provide
      protective benefit in the treatment of PD.

PMID- 15236402
TI  - Increased susceptibility of S100B transgenic mice to perinatal hypoxia-ischemia.
AB  - S100B is a glial-derived protein that is a well-established biomarker for
      severity of neurological injury and prognosis for recovery. Cell-based and
      clinical studies have implicated S100B in the initiation and maintenance of a
      pathological, glial-mediated proinflammatory state in the central nervous system.
      However, the relationship between S100B levels and susceptibility to neurological
      injury in vivo has not been determined. We used S100B transgenic (Tg) and
      knockout (KO) mice to test the hypothesis that overexpression of S100B increases
      vulnerability to cerebral hypoxic-ischemic injury and that this response
      correlates with an increase in neuroinflammation from activated glia. Postnatal
      day 8 Tg mice subjected to hypoxia-ischemia showed a significant increase in
      mortality compared with KO and wild-type mice. Tg mice also exhibited greater
      cerebral injury and volume loss in the ischemic hemisphere after an 8-day
      recovery, as assessed by histopathology and magnetic resonance imaging.
      Measurement of glial fibrillary acidic protein and S100B levels showed a
      significant increase in the Tg mice, consistent with heightened glial activation
      and neuroinflammation in response to injury. This is the first demonstration to
      our knowledge that overexpression of S100B in vivo enhances pathological response
      to injury.

PMID- 15236403
TI  - Prevention of neuropathology in the mouse model of Hurler syndrome.
AB  - A defect of the lysosomal enzyme alpha-L-iduronidase (IDUA) interrupts heparan
      and dermatan sulfate degradation and causes neuropathology in children with
      severe forms of mucopolysaccharidosis type I (MPSI, Hurler syndrome). Enzyme
      substitution therapy is beneficial but ineffective on the central nervous system.
      We could deliver the missing enzyme to virtually the entire brain of MPSI mice
      through a single injection of gene transfer vectors derived from adenoassociated
      virus serotype 2 (AAV2) or 5 (AAV5) coding for human IDUA. This result was
      reproducibly achieved with both vector types in 46 mice and persisted for at
      least 26 weeks. Success was more frequent, enzyme activity was higher, and
      corrected areas were broader with AAV5 than with AAV2 vectors. Treatment
      presumably reversed and certainly prevented the accumulation of GM2 and GM3
      gangliosides, which presumably participates to neuropathology. Lysosomal
      distension, which already was present at the time of treatment, had disappeared
      from both brain hemispheres and was minimal in the cerebellum in mice analyzed 26
      weeks after injection. This study shows that pathology associated with MPSI can
      be prevented in the entire mouse brain by a single AAV vector injection,
      providing a preliminary evaluation of the feasibility of gene therapy to stop
      neuropathology in Hurler syndrome.

PMID- 15236404
TI  - Long-term effect of motor cortical repetitive transcranial magnetic stimulation
      [correction].
AB  - Repetitive transcranial magnetic stimulation (rTMS) recently has been assessed as
      a noninvasive treatment modality for movement and psychiatric disorders, whereas
      the mechanism underlying the therapeutic effects is not fully understood. Studies
      in rodents showed lasting functional changes in some selected regions, such as
      limbic-associated structures, but unfocused brain stimulation did not clarify the
      regional effects. To address the topographical and temporal profiles of the
      effects on glucose metabolism in primate brain, we performed rTMS and repeated
      (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) before, during,
      and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a
      total of 2,000 pulses of 5 Hz-rTMS over the right precentral gyrus using a small
      sized eight-figured coil that induced a localized electrical field. Voxel-based
      analysis in a standard space of the macaque brain showed statistically robust
      changes in FDG uptake: a decrease in the motor/premotor cortices and an increase
      in the limbic-associated areas involving the anterior/posterior cingulate, and
      orbitofrontal cortices. Interestingly, these uptake changes continued for at
      least 8 days and the magnitude of the lasting effects in the limbic-related areas
      was negatively correlated across subjects with those in the motor/premotor
      cortices. The results demonstrate that motor rTMS has a long-term lasting effect
      on motor-related regions and distant limbic-related areas via functional
      connections.

PMID- 15236405
TI  - Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene
      mutations.
AB  - Nemaline myopathy (NM) is the most common of several congenital myopathies that
      present with skeletal muscle weakness and hypotonia. It is clinically
      heterogeneous and the diagnosis is confirmed by identification of nemaline bodies
      in affected muscles. The skeletal muscle alpha-actin gene (ACTA1) is one of five
      genes for thin filament proteins identified so far as responsible for different
      forms of NM. We have screened the ACTA1 gene in a cohort of 109 unrelated
      patients with NM. Here, we describe clinical and pathological features associated
      with 29 ACTA1 mutations found in 38 individuals from 28 families. Although ACTA1
      mutations cause a remarkably heterogeneous range of phenotypes, they were
      preferentially associated with severe clinical presentations (p < 0.0001). Most
      pathogenic ACTA1 mutations were missense changes with two instances of single
      base pair deletions. Most patients with ACTA1 mutations had no prior family
      history of neuromuscular disease (24/28). One severe case, caused by compound
      heterozygous recessive ACTA1 mutations, demonstrated increased alpha-cardiac
      actin expression, suggesting that cardiac actin might partially compensate for
      ACTA1 abnormalities in the fetal/neonatal period. This cohort also includes the
      first instance of an ACTA1 mutation manifesting with adult-onset disease and two
      pedigrees exhibiting potential incomplete penetrance. Overall, ACTA1 mutations
      are a common cause of NM, accounting for more than half of severe cases and 26%
      of all NM cases in this series.

PMID- 15236406
TI  - B-lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis
      cerebrospinal fluid.
AB  - The CD19+ B-lymphocyte and CD138+ plasma cell repertoires in cerebrospinal fluid
      from four patients with monosymptomatic optic neuritis (ON) were analyzed by
      single-cell reverse transcriptase polymerase chain reaction. Amplified heavy (H)-
      and light (L)-chain antibody segments were sequenced and used to identify the
      rearranged germline and J segment of closest homology. Both the B-cell and plasma
      cell repertoires from ON cerebrospinal fluid demonstrated significant clonal
      expansion. Up to 75% of the amplified H- and L-chain sequences were contained in
      overrepresented populations and were somatically mutated, consistent with an
      antigen-targeted response. The relationship between clonal populations within the
      CD19+ B lymphocyte and CD138+ plasma cell populations suggests ongoing mutational
      pressure to refine antigen binding. Our observations demonstrate that an antigen
      driven clonal B-lymphocyte and plasma cell response is prominent in the initial
      stages of central nervous system demyelination and suggest that detection of the
      disease-relevant antigens in ON may bear on the inciting antigens in chronic
      inflammatory disorders such as multiple sclerosis.

PMID- 15236407
TI  - High-frequency oscillations recorded in human medial temporal lobe during sleep.
AB  - The presence of fast ripple oscillations (FRs, 200-500 Hz) has been confirmed in
      rodent epilepsy models but has not been observed in nonepileptic rodents,
      suggesting that FRs are associated with epileptogenesis. Although studies in
      human epileptic patients have reported that both FRs and ripples (80-200 Hz)
      chiefly occur during non-rapid eye movement sleep (NREM), and that ripple
      oscillations in human hippocampus resemble those found in nonprimate slow wave
      sleep, quantitative studies of these oscillations previously have not been
      conducted during polysomnographically defined sleep and waking states.
      Spontaneous FRs and ripples were detected using automated computer techniques in
      patients with medial temporal lobe epilepsy during sleep and waking, and results
      showed that the incidence of ripples, which are thought to represent normal
      activity in animal and human hippocampus, was similar between epileptogenic and
      nonepileptogenic temporal lobe, whereas rates of FR occurrence were significantly
      associated with epileptogenic areas. The generation of both FRs and ripples
      showed the highest rates of occurrence during NREM sleep. During REM sleep,
      ripple rates were lowest, whereas FR rates remained elevated and were equivalent
      to rates observed during waking. The predominance of FRs within the epileptogenic
      zone not only during NREM sleep, but also during epileptiform-suppressing
      desynchronized episodes of waking and REM sleep supports the view that FRs are
      the product of pathological neuronal hypersynchronization associated with seizure
      generating areas.

PMID- 15236408
TI  - MR molecular imaging of early endothelial activation in focal ischemia.
AB  - Focal ischemia followed by reperfusion initiates a harmful P- and E-selectin
      mediated recruitment of leukocytes in brain microvasculature. In this study, we
      tested whether a novel magnetic resonance (MR) contrast agent (Gd-DTPA-sLe(x) A),
      which is designed to bind to activated endothelium could be detected by MR
      imaging (MRI) in a focal stroke mouse model. MRIs (9.4T) of the brain were
      acquired 24 hours after transient middle cerebral artery occlusion. T1 maps were
      acquired repeatedly before and up to 1.5 hours after the intravenous injection of
      either Gd-DTPA or Gd-DTPA-sLe(x) A. Analysis of images included a pixel-by-pixel
      subtraction of T1 maps from the precontrast T1 maps and quantification of T1
      within the ischemic area. After injection of Gd-DTPA-sLe(x) A, T1 decreased
      compared with precontrast levels, and an interhemispheric difference between the
      pre-post contrast T1 developed within the stroke lesion at a mean time of 52
      minutes after injection (p < 0.05). Animals injected with Gd-DTPA did not exhibit
      changes in T1 signal intensity between regions of the ipsilateral and
      contralateral hemispheres, indicating that the reductions in T1 observed with Gd
      DTPA-sLe(x) A were unrelated to blood-brain barrier breakdown. Fluorescent
      labeled sLe(x) A administered intravenously was observed to bind to the
      endothelium of injured but not control brain. The study suggests that the
      contrast agent Gd-DTPA-sLe(x) A can be used to visualize early endothelial
      activation after transient focal ischemia in vivo with MRI.

PMID- 15236409
TI  - The interleukin 1beta gene promoter polymorphism (-511) acts as a risk factor for
      psychosis in Alzheimer's dementia.
AB  - The explanation for why some patients develop psychotic change in Alzheimer's
      disease (AD) is unclear. "Psychosis-modifier genes" may act in the setting of
      neurodegeneration to produce AD plus psychosis in a similar way to how genetic
      modulation during neurodevelopment leads to schizophrenia. Because there is
      increasing interest in the common disruption of cytokine pathways seen in both AD
      and schizophrenia, we tested the association between the functional interleukin
      1beta -511 promoter polymorphism with delusions and hallucinations in AD.
      Significant associations between psychotic symptoms and the CC genotype (p =
      0.001 - p = 0.043) and C allele (p = 0.014 vs p = 0.048) were found, thus
      confirming the previously noted increased risk in schizophrenia.

PMID- 15236410
TI  - Sequence-dependent and independent inhibition specific for mutant ataxin-3 by
      small interfering RNA.
AB  - In Machado-Joseph disease (MJD) gene, there is a C/G polymorphism immediately
      after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C,
      whereas about half of wild-type alleles are followed by G. Using this C/G
      polymorphism, we have engineered the small interfering RNA (siRNA) which
      decreased the expression of mutant ataxin-3, Q79C, by 96.0%, whereas there was
      minimal reduction on that of the wild type, Q22G (5.9%). Furthermore,
      unexpectedly, the expression of another wild-type allele, Q22C, was also much
      less suppressed (22.5%) by this siRNA possibly due to difference of the secondary
      structure of the target RNA. This is the first report of sequence-independent
      discrimination of mutant and wild-type alleles by siRNA.

PMID- 15236411
TI  - Is benign rolandic epilepsy genetically determined?
AB  - Benign rolandic epilepsy (BRE) is considered to be a genetically determined
      idiopathic partial epilepsy. We studied twins with BRE and compared the
      concordance with a twin sample of idiopathic generalized epilepsy (IGE). All
      eight BRE pairs (six monozygous [MZ], two dizygous [DZ]) were discordant. MZ
      pairwise concordance was 0 (95% confidence interval [CI], 0-0.4) for BRE compared
      with 0.7 (95% CI, 0.5-0.9) for 26 IGE MZ pairs. Our data suggest that
      conventional genetic influences in BRE are considerably less than for IGE, and
      other mechanisms need to be explored.

PMID- 15236412
TI  - Abnormal lysosomal and ubiquitin-proteasome pathways in 19p13.3 distal myopathy.
AB  - We describe a second large Italian kindred with autosomal dominant vacuolar
      myopathy characterized by variable severity, adult-onset weakness of distal limb
      muscles, and no cardiac involvement. At least 19 individuals over four
      generations are affected. Histopathological and immunochemical features of the
      vacuoles, present in many fibers, indicate protein degradation abnormalities with
      dysregulation of the lysosomal pathway and activation of the ubiquitin
      proteasomal pathway. Linkage analysis localized the defect to the 19p13.3 locus
      in a region with no known genes. We speculate that the primary defect may be an
      abnormality in the lysosomal degradation pathway or related components.

PMID- 15236413
TI  - Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation.
AB  - Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC
      mutation (A802V) were treated by assisted respiration and/or sodium benzoate with
      or without ketamine and had transient neonatal or absent symptoms and normal
      developmental outcome, despite persisting biochemical evidence of nonketotic
      hyperglycinemia. This exceptional outcome may be related to the high residual
      activity of the mutant protein (32% of wild type) and therapeutic intervention
      during a critical period of heightened brain exposure and sensitivity to glycine.

PMID- 15236414
TI  - POMGnT1 gene alterations in a family with neurological abnormalities.
AB  - Muscle-eye-brain disease (MEB), is caused by mutations in the POMGnT1 gene. We
      describe a white family with two siblings affected with congenital hypotonia
      early-onset glaucoma, and psychomotor delays. Brain magnetic resonance images
      (MRIs) showed hydrocephalus, bilateral frontal polymicrogyria, abnormal
      cerebellum, and characteristic flattened dystrophic pons. We identified novel
      POMGnT1 gene alterations in this family. Both affected siblings were found to be
      compound hetrozygotes and carried two missense changes inherited from their
      mother and one missense change (p.R442C) inherited from their father. Our
      findings further define the phenotypic spectrum of MEB and its occurrence in the
      US population.

PMID- 15236415
TI  - Systemic exposure to proteasome inhibitors causes a progressive model of
      Parkinson's disease.
AB  - Environmental toxins have been implicated in the etiology of Parkinson's disease.
      Recent findings of defects in the ubiquitin-proteasome system in hereditary and
      sporadic forms of the illness suggest that environmental proteasome inhibitors
      are candidate PD-inducing toxins. Here, we systemically injected six doses of
      naturally occurring (epoxomicin) or synthetic (Z-lle-Glu(OtBu)-Ala-Leu-al [PSI])
      proteasome inhibitors into adult rats over a period of 2 weeks. After a latency
      of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia,
      rigidity, tremor, and an abnormal posture, which improved with apomorphine
      treatment. Positron emission tomography demonstrated reduced carbon-11-labeled
      2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding to dopaminergic
      nerve terminals in the striatum, indicative of degeneration of the nigrostriatal
      pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic
      cell death with apoptosis and inflammation in the substantia nigra pars compacta.
      In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor
      nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative
      sites, intracytoplasmic, eosinophilic, alpha-synuclein/ubiquitin-containing,
      inclusions resembling Lewy bodies were present in some of the remaining neurons.
      This animal model induced by proteasome inhibitors closely recapitulates key
      features of PD and may be valuable in studying etiopathogenic mechanisms and
      putative neuroprotective therapies for the illness.

PMID- 15236416
TI  - Spinocerebellar ataxia type 17 repeat in patients with Huntington's disease-like
      and ataxia.

PMID- 15236418
TI  - Seizure-induced plasticity and adverse long-term effects of early-life seizures.

PMID- 15236422
TI  - A latent normal distribution model for analysing ordinal responses with
      applications in meta-analysis.
AB  - We consider the comparison of two treatments (or a treatment and a
      control/placebo) with responses that are classified into ordinal categories. By
      operating on the assumption that the responses are manifestations of some
      underlying continuous variables and that the definitions of the categories for
      the treatment group and the placebo group are the same in the same clinical test
      centre, we develop a model to examine the possible treatment effects. These
      treatment effects can be identified as location effect or dispersion effect. The
      method can be generalized to analyse clinical test results coming from different
      centres, where each centre may have its own standard in classifying responses.
      The method is technically undemanding and can be implemented in a very simple and
      straightforward way by using easily accessible software that can be downloaded at
      no cost. Real data sets are analysed for illustration.

PMID- 15236423
TI  - Modelling associations between time-to-event responses in pilot cancer clinical
      trials using a Plackett-Dale model.
AB  - This work was motivated by the need to find surrogate endpoints for survival of
      patients in oncology studies. The goal of this article is to determine
      associations between five time-to-event outcomes coming from three clinical
      trials for non-small cell lung cancer. To this end, we propose to use the
      multivariate Dale model for time-to-event data introduced by Tibaldi et al.
      (Stat. Med. 2003). We fit the model to these data, using a pseudo-likelihood
      approach to estimate the model parameters. We evaluate and compare the
      performance of different dimensional models and we relate the Dale model
      association parameter, i.e. the odds ratio, to well-known quantities such as
      Kendall's tau and Spearman's rho. Finally, the results are discussed with a
      perspective on surrogate marker validation. Some suggestions are made regarding
      further studies in this field.

PMID- 15236424
TI  - Multivariate estimation of the relative dose potency.
AB  - As a follow-up to a previous publication we illustrate how multivariate analysis
      of dose-response trials can be done, providing single number, relative dose
      potency, results for the comparison between two treatments, also when a number of
      variables are measured.

PMID- 15236425
TI  - Monitoring change in spatial patterns of disease: comparing univariate and
      multivariate cumulative sum approaches.
AB  - Prospective disease surveillance has gained increasing attention, particularly in
      light of recent concern for quick detection of bioterrorist events. Monitoring of
      health events has the potential for the detection of such events, but the
      benefits of surveillance extend much more broadly to the quick detection of
      change in public health. In this paper, univariate and multivariate cumulative
      sum methods for disease surveillance are compared. Although the univariate method
      has been previously used in the context of health surveillance, the multivariate
      method has not. The univariate approach consists of simultaneously and
      independently monitoring the disease rate in each region; the multivariate
      approach accounts explicitly for any covariation between regions. The univariate
      approaches are limited by their lack of ability to account for the spatial
      autocorrelation of regional data; the multivariate methods are limited by the
      difficulty in accurately specifying the multiregional covariance structure. The
      methods are illustrated using both simulated data and county-level data on breast
      cancer in the northeastern United States. When the degree of spatial
      autocorrelation is low, the univariate method is generally better at detecting
      changes in rates that occur in a small number of regions; the multivariate is
      better when change occurs in a large number of regions.

PMID- 15236426
TI  - Analysis of longitudinal studies with death and drop-out: a case study.
AB  - The analysis of longitudinal data has recently been an active area of
      biostatistical research. Two main approaches to analysis have emerged, the first
      concentrating on modelling evolution of marginal distributions of the main
      response variable of interest and the other on subject-specific trajectories. In
      epidemiology the analysis is usually complicated by missing data and by death of
      study participants. Motivated by a study of cognitive decline in the elderly,
      this paper argues that these two types of incomplete follow-up may need to be
      treated differently in the analysis, and proposes an extension to the marginal
      modelling approach. The problem of informative drop-out is also discussed. The
      methods are implemented in the 'Stata' statistical package.

PMID- 15236427
TI  - Robust Bayesian prediction of subject disease status and population prevalence
      using several similar diagnostic tests.
AB  - Sometimes several diagnostic tests are performed on the same population of
      subjects with the aim of assessing disease status of individuals and the
      prevalence of the disease in the population, but no test is a reference test.
      Although the diagnostic tests may have the same biological underpinnings, test
      results may disagree for some specific animals. In that case, it may be difficult
      to determine disease status for individual subjects, and consequently population
      prevalence estimation becomes difficult. In this paper, we propose a robust
      method of estimating disease status and prevalence that uses heavy-tailed
      sampling distributions in a hierarchical model to protect against the influence
      of conflicting observations on inferences. If a subject has a test outcome that
      is discordant with the other test results then it is downweighted in diagnosing a
      subject's disease status, and for estimating disease prevalence. The amount of
      downweighting depends on the degree of conflict among the test results for the
      subject.

PMID- 15236429
TI  - Advantages to transforming the receiver operating characteristic (ROC) curve into
      likelihood ratio co-ordinates.
AB  - Traditionally, the receiver operating characteristic (ROC) curve for a diagnostic
      test plots true positives (sensitivity) against false positives (one minus
      specificity). However, this representation brings with it several drawbacks. A
      transformation to positive and negative likelihood ratio co-ordinates, scaled by
      base-ten logarithms, offers several advantages. First we motivate the use of
      positive and negative likelihood ratios, emphasizing their relationship to
      modification of the odds ratio. Then we highlight properties of likelihood ratios
      using the traditional ROC axes. Finally, we demonstrate ROC curves and their
      properties after conversion to likelihood ratio co-ordinates. These graphs do not
      waste space for tests lacking diagnostic power, and offer a simple visual
      assessment of a test's impact on the odds ratio.

PMID- 15236428
TI  - Diagnostic test accuracy and prevalence inferences based on joint and sequential
      testing with finite population sampling.
AB  - The two-test two-population model, originally formulated by Hui and Walter, for
      estimation of test accuracy and prevalence estimation assumes conditionally
      independent tests, constant accuracy across populations and binomial sampling.
      The binomial assumption is incorrect if all individuals in a population e.g.
      child-care centre, village in Africa, or a cattle herd are sampled or if the
      sample size is large relative to population size. In this paper, we develop
      statistical methods for evaluating diagnostic test accuracy and prevalence
      estimation based on finite sample data in the absence of a gold standard.
      Moreover, two tests are often applied simultaneously for the purpose of obtaining
      a 'joint' testing strategy that has either higher overall sensitivity or
      specificity than either of the two tests considered singly. Sequential versions
      of such strategies are often applied in order to reduce the cost of testing. We
      thus discuss joint (simultaneous and sequential) testing strategies and inference
      for them. Using the developed methods, we analyse two real and one simulated data
      sets, and we compare 'hypergeometric' and 'binomial-based' inferences. Our
      findings indicate that the posterior standard deviations for prevalence (but not
      sensitivity and specificity) based on finite population sampling tend to be
      smaller than their counterparts for infinite population sampling. Finally, we
      make recommendations about how small the sample size should be relative to the
      population size to warrant use of the binomial model for prevalence estimation.

PMID- 15236430
TI  - The multiple-record systems estimator when registrations refer to different but
      overlapping populations.
AB  - In multiple-record systems estimation it is usually assumed that all registration
      relate to the same population. In this paper, we develop a method which can be
      used when the registrations relate to different populations, in the sense that
      they cover, for example, different time periods or regions. We show that under
      certain conditions ignoring that the registrations relate to different
      populations results in correct estimates of population size. The EM algorithm is
      presented as a method that can be used for more general problems. The parametric
      bootstrap is used to construct a confidence interval. The proposed method is then
      applied to a data set with five registrations of neural tube defects, that cover
      different time periods.

PMID- 15236431
TI  - Sample size and power for McNemar's test with clustered data.
AB  - McNemar's test is used to compare the distribution of two paired binary random
      variables. When the data are clustered adjustment is needed to ensure that it is
      still a valid test. This article presents two approximations for calculating the
      power and sample size for the adjusted McNemar's test for clustered data, working
      with a particular adjustment. A simulation study is conducted to demonstrate the
      accuracy of these approximations. The method is also applied to the design of a
      study involving positron emission tomography in detecting metastatic colorectal
      cancer and sensitivity of sample size computations to the design parameters are
      explored in this context.

PMID- 15236432
TI  - Quantile regression via vector generalized additive models.
AB  - One of the most popular methods for quantile regression is the LMS method of Cole
      and Green. The method naturally falls within a penalized likelihood framework,
      and consequently allows for considerable flexible because all three parameters
      may be modelled by cubic smoothing splines. The model is also very
      understandable: for a given value of the covariate, the LMS method applies a Box
      Cox transformation to the response in order to transform it to standard
      normality; to obtain the quantiles, an inverse Box-Cox transformation is applied
      to the quantiles of the standard normal distribution. The purposes of this
      article are three-fold. Firstly, LMS quantile regression is presented within the
      framework of the class of vector generalized additive models. This confers a
      number of advantages such as a unifying theory and estimation process. Secondly,
      a new LMS method based on the Yeo-Johnson transformation is proposed, which has
      the advantage that the response is not restricted to be positive. Lastly, this
      paper describes a software implementation of three LMS quantile regression
      methods in the S language. This includes the LMS-Yeo-Johnson method, which is
      estimated efficiently by a new numerical integration scheme. The LMS-Yeo-Johnson
      method is illustrated by way of a large cross-sectional data set from a New
      Zealand working population.

PMID- 15236433
TI  - Effects and non-effects of paired identical observations in comparing proportions
      with binary matched-pairs data.

PMID- 15236434
TI  - Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant
      rats and rabbits.
AB  - Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention
      deficit hyperactivity disorder (ADHD) and narcolepsy. The present report
      describes the determination of plasma concentrations of D-threo- and L-threo
      enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats
      and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH
      (racemate). A previously reported chiral liquid chromatography tandem mass
      spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of
      1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic
      MPH were selected for the rat study. An over-proportional increase in exposure
      was observed with increasing doses of MPH racemate, the effect being more
      profound with the D- than the L-enantiomer. In contrast, Cmax values of both
      enantiomers were approximately proportional to the dose. Oral (gavage) doses of
      20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D
      isomer, an over-proportional increase in exposure was observed with increasing
      doses of MPH racemate. Conversely, for the L-isomer, a slight under
      proportionality was detected in exposure with increasing doses of D,L-MPH. For
      mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of
      MPH racemate, the D-isomer appeared to be over-proportional. Herein, the
      experimental design and observed TK parameters in each study are presented.

PMID- 15236435
TI  - A method for determination of dimethyl benzoylphenyl urea (BPU) in human plasma
      by using LC/UV.
AB  - Dimethyl benzoylphenyl urea (BPU) inhibited tubulin polymerization, caused
      microtubule depolymerization in vitro and demonstrated activity against solid
      tumors. BPU is being tested in phase I clinical trials. A rapid and specific
      method using LC/UV has been developed for quantitation of BPU in human heparin
      containing plasma to perform pharmacokinetic and pharmacodynamic studies. BPU is
      extracted from plasma into acetonitrile:n-butyl-chloride using paclitaxel as the
      internal standard and separated on a Waters Symmetry C18 (3.9 x 150 mm, 5 microm)
      column with acetonitrile-water mobile phase (70:30, v/v) using isocratic flow at
      1 mL/min for a run time of 5 min. Ultraviolet detection was utilized and
      performed at 225 nm for BPU and paclitaxel. The retention times were 1.9 min for
      paclitaxel and 4.1 min for BPU. Calibration curves were generated over the range
      of 0.01-10 microg/mL with coefficient of determination of > 0.99. The values for
      within-day and between-day precision were < or = 17.0% at the LLOQ and < or =
      7.4% at the low, medium and high quality controls; accuracy was +/- 5.4%.
      Following administration of BPU 320 mg as a weekly oral dose to a patient with
      advanced solid tumor malignancies, the maximum plasma concentration was 2 micro
      g/mL and concentrations were quantifiable up to 168 h after administration. The
      lower limit of quantitation of 0.01 microg/mL allows for successful measurement
      of plasma concentrations in patients.

PMID- 15236436
TI  - Determination of rhein, baicalin and berberine in traditional Chinese medicinal
      preparations by capillary electrophoresis with two-marker technique.
AB  - A CZE method for the identification and determination of three bioactive
      components, rhein, baicalin and berberine, was developed, with 10 mM borate at pH
      9.20 as background electrolyte and direct UV detection at 254 nm. The two-marker
      (glycyrrhizin acid and cefalexin) technique was used to improve the repeatability
      of analysis. When the migration indices were used, the repeatability was greatly
      enhanced compared with migration times. The apparent dissociation contents of
      rhein and baicalin were also obtained. This method has been successfully applied
      to the simultaneous analysis of the three components with the recoveries from
      96.7% to 104.6%.

PMID- 15236437
TI  - Simultaneous determination of estramustine phosphate and its four metabolites in
      human plasma by liquid chromatography-ionspray mass spectrometry.
AB  - A sensitive and selective method, using liquid chromatography-ionspray mass
      spectrometry, was developed and validated for the simultaneous determination of
      Estracyt (estramustine phosphate) and its four metabolites, estramustine,
      estromustine, estrone and estradiol, in human plasma. Deuterated internal
      standards were available for all analytes. The five compounds were extracted from
      plasma by protein precipitation with acetonitrile. The chromatographic separation
      was performed using a Zorbax SB C18, (150 x 4.6 mm i.d., 5 microm) reversed-phase
      column under gradient conditions with a mobile phase containing 2 mm ammonium
      acetate buffer (pH 6.8) and acetonitrile. MS detection was by electrospray
      ionization with multiple reaction monitoring in the positive ion mode for
      estramustine phosphate, estromustine and estramustine, and in the negative ion
      mode for estrone and estradiol. The limit of quantitation was 10 ng/mL for
      estramustine phosphate, 3 ng/mL for estromustine, estramustine and estrone and 30
      ng/mL for estradiol. Linearity was verified from these LLOQs up to about 4000
      ng/mL for the parent drug and 2000 ng/mL for the metabolites. Inter-day precision
      and accuracy values were all less than 15%. This assay was applied successfully
      to the routine analysis of human plasma samples collected in cancer patients
      administered estramustine phosphate intravenously.

PMID- 15236438
TI  - Validated capillary electrophoretic method for the analysis of ivermectin in
      plasma after intragastric administration in pigs and horses.
AB  - A capillary electrophoretic (CE) method has been developed for the determination
      of ivermectin (CAS 70288-86-7), a new generation drug with antiparasitic
      activity, in pig and horse plasma. The method was statistically validated for its
      linearity, accuracy, precision and selectivity. The linear range was from 1 to 30
      ng mL(-1) with correlation coefficients greater than 0.999. The limit of
      detection was 0.3 ng mL(-1), while the quantitative limit was 1 ng mL(-1), using
      a 0.5 mL sample size. The validated procedure was used to determination of
      pharmacokinetic parameters of ivermectin after ingestion of 0.1 mg for pigs and
      0.2 mg dose per kg body weight for horses, respectively. Studies were performed
      on a group of eight pigs and six horses. There were no significant differences
      between pigs and horses in any of the estimated pharmacokinetic parameters.

PMID- 15236439
TI  - The bioequivalence study of baclofen and lioresal tablets using capillary
      electrophoresis.
AB  - A simple and robust analytical method for rapid separation and sensitive
      quantification of baclofen in human plasma by capillary electrophoresis technique
      was developed. Electrophoretic separation was optimized and successfully
      performed using simple sodium tetraborate aqueous solution. Observed detection
      limit in biological material was 10 ng. Using UV detection at 200 nm excellent
      linearity (r = 0.999) was observed over the concentration range from 0.025 to 1.0
      microg mL(-1). The described method has been validated and applied to the
      quantitative determination of baclofen in human plasma. The bioavailability of
      Baclofen (Polpharma) and Lioresal (Novartis) in 18 healthy volunteers was
      investigated. The results indicate bioequivalence of the reference and Baclofen
      preparations.

PMID- 15236440
TI  - Simultaneous determination of four bufadienolides in human liver by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for the simultaneous
      quantitation of four bufadienolides-cinobufotalin, bufalin, cinobufagin and
      resibufogenin-in human liver was investigated. The procedure involved solid phase
      extraction of human liver with an Oasis HLB cartridge coupled with reversed-phase
      HPLC and photodiode array detection. Recoveries obtained from spiked liver for
      the bufadienolides were better than 70%. The linearity was studied up to 1.2
      mg/kg and the detection limits of the method were 0.4 ng for cinobufotalin and
      bufalin and 0.5 ng for cinobufagin and resibufogenin. The developed method was
      successfully applied to a lethal poisoning case.

PMID- 15236441
TI  - Liquid chromatographic and mass spectrometric analysis of human serum acid alpha
      1-glycoprotein.
AB  - Human serum acid alpha-1-glycoprotein (AGP, orosomucoid) content of healthy
      individuals and cancer patients was measured, isolated and purified using a
      protocol of fast and biocompatible sample preparation, ion exchange and dye
      ligand affinity chromatographic methods. In comparison to the healthy individuals
      significantly higher serum AGP levels were found in a wide spectrum of cancer
      patients, indicating its diagnostic value in the malignant disease.
      Oligosaccharide content of AGP samples was separated following PNGase F enzyme
      digestion and analysed by RP-HPLC and MALDI-TOF mass spectrometry. RP-HPLC and
      MALDI-TOF mass spectrometric analysis of sugar constituents of AGP specimen
      originated from selected cancer patients with high serum AGP levels indicated the
      appearance of anomal distribution of bi-, tri- and tetra-antennary
      oligosaccharide structures compared to the healthy controls.

PMID- 15236442
TI  - HPLC microdetermination of flurbiprofen enantiomers in plasma with a glycopeptide
      type chiral stationary phase column.
AB  - A rapid and stereospecific HPLC micromethod to quantify flurbiprofen enantiomers
      was developed. Both flurbiprofen enantiomers and indomethacin, used as internal
      standard, were extracted with methylene chloride from 100 microL of acidified
      plasma. The resolution of the R- and S-forms was performed on a bonded vancomycin
      chiral stationary phase (Chirobiotic V) with 20% of tetrahydrofuran in ammonium
      nitrate (100 mM, pH 5) as mobile phase. Calibration curves were linear in the
      range 0.5-10 microg/mL for both enantiomers. A good accuracy (< or = 5%) was
      obtained for all quality controls, with intra-day and inter-day variation
      coefficients equal or less than 7.7%. Recovery of both enantiomers was found in
      the range 77.4-86.3%. The lower limit of quantitation was 0.25 microg/mL for both
      enantiomers, without interference of endogenous components. This validated
      micromethod has been successfully applied for quantifying R- flurbiprofen and S-
      flurbiprofen in rat plasma.

PMID- 15236443
TI  - Determination of the liver cytosolic proteins that bind to p-hydroxyacetophenone.
AB  - The purpose of the present study was to determine the proteins that bind to
      acetophenones in the liver. Immobilized p-hydroxyacetophenone (p-HAP) was used as
      a ligand of affinity chromatography. Analysis using sodium dodesyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that five polypeptides
      in the liver cytosolic fraction specifically bound to the p-HAP matrix. These
      polypeptides were digested with Lys-specific protease and used to generate
      peptide maps by reversed-phase high-performance liquid chromatography.
      Consequently, identification from a data base of protein sequences revealed that
      the five polypeptides were glycogen phosphorylase, cytosolic aldehyde
      dehydrogenase, adenosine kinase, class I alcohol dehydrogenase and glutathione S
      transferase A2. In addition to p-HAP, acetylsalicylic acid also displayed a
      prominent ability to elute these five enzymes from the p-HAP affinity column
      loaded with the cytosolic fraction of the liver. Thus, p-HAP has affinities to
      the above liver enzymes and is a useful ligand for analysis of them.

PMID- 15236444
TI  - Analytical derivation of time required for dissolution of monodisperse drug
      particles.

PMID- 15236445
TI  - Biowaiver monographs for immediate release solid oral dosage forms based on
      biopharmaceutics classification system (BCS) literature data: verapamil
      hydrochloride, propranolol hydrochloride, and atenolol.
AB  - Literature data related to the Biopharmaceutics Classification System (BCS) are
      presented on verapamil hydrochloride, propranolol hydrochloride, and atenolol in
      the form of BCS-monographs. Data on the qualitative composition of immediate
      release (IR) tablets containing these active substances with a Marketing
      Authorization (MA) in the Netherlands (NL) are also provided; in view of these
      MA's the assumption was made that these tablets were bioequivalent to the
      innovator product. The development of a database with BCS-related data is
      announced by the International Pharmaceutical Federation (FIP).

PMID- 15236446
TI  - Novel rearrangements of an N-oxide degradate formed from oxidation of a
      morpholine acetal substance P antagonist.
AB  - Compound 1 [5-[2(R)-[1(R)-(3,5-bistrifluoromethylphenyl) ethoxy]-3(s)-(4
      fluorophenyl)morpholin-4-ylmethyl]-3h-[1,2,3] triazol-4-ylmethyl]dimethylamine
      represents a new class of potent, orally active substance P antagonists, which
      possess a characteristic structural feature-a cis-2-alkoxy-3-arylmorpholine core.
      The oxidative degradation of 1 in drug substance and formulations was found to
      occur through the two trialkylamine oxides, which undergo secondary degradations
      to give rise to observed degradation products. In this study, the five primary
      degradation products of the N-oxide 2 formed from the oxidation of the morpholine
      core of 1 were identified by LC/MS and MS/MS. The N-oxide 2 undergoes novel
      thermal rearrangements, which were proposed to follow elimination/addition
      mechanisms. An unusual, facile [1,3]-sigmatropic rearrangement was also
      demonstrated.

PMID- 15236447
TI  - Release from polymeric prodrugs: linkages and their degradation.
AB  - Polymeric prodrugs have evolved into a very useful class of drug delivery agents.
      Numerous polymeric prodrugs have been prepared for applications ranging from
      passive drug targeting to controlled release. The mechanistic aspects of the
      release processes, however, have not been clearly delineated. This review
      highlights the salient features of the chemical reactions that are responsible
      for drug release from these systems. The mechanisms of release from polymeric
      prodrugs employing various chemical linkages, esters, carbonates, carbamates, C=N
      linkage and amides, are discussed.

PMID- 15236448
TI  - Current methods for attaching targeting ligands to liposomes and nanoparticles.
AB  - Liposomes and nanoparticles have emerged as versatile carrier systems for
      delivering active molecules in the organism. These colloidal particles have
      demonstrated enhanced efficacy compared to conventional drugs. However, the
      design of liposomes and nanoparticles with a prolonged circulation time and
      ability to deliver active compounds specifically to target sites remains an
      ongoing research goal. One interesting way to achieve active targeting is to
      attach ligands, such as monoclonal antibodies or peptides, to the carrier. These
      surface-bound ligands recognize and bind specifically to target cells. To this
      end, various techniques have been described, including covalent and noncovalent
      approaches. Both in vitro and in vivo studies have proved the efficacy of the
      concept of active targeting. The present review summarizes the most common
      coupling techniques developed for binding homing moieties to the surface of
      liposomes and nanoparticles. Various coupling methods, covalent and noncovalent,
      will be reviewed, with emphasis on the major differences between the coupling
      reactions, on their advantages and drawbacks, on the coupling efficiency
      obtained, and on the importance of combining active targeting with long
      circulating particles.

PMID- 15236449
TI  - Development of solid lipid nanoparticles containing ionically complexed
      chemotherapeutic drugs and chemosensitizers.
AB  - The purpose of this study was to develop and characterize a solid lipid
      nanoparticle (SLN) system containing an anionic polymer for the delivery of
      cationic antineoplastic agents and chemosensitizers. Ionic complexation was
      utilized to enhance the loading of these highly water-soluble drugs. The
      influence of anionic compounds and polymers on drug partition and loading into
      SLNs was investigated, and dextran sulfate (DS) was found to be the most suitable
      among those studied. SLNs loaded with doxorubicin and various model
      chemosensitizers (e.g., verapamil) were thus prepared by incorporating DS using a
      microemulsion method. The particle size was measured with photon correlation
      spectroscopy. The mean diameter of the SLNs ranged from 180 to 300 nm, depending
      on the type and content of the drug and the polymer. The particles possessed
      weakly negative surface charges as determined by zeta potential measurements.
      Most polymer-loaded SLNs released half of the drug in the first a few hours and
      the remaining drug in 15 h or more. The presence of counterions in the medium,
      especially divalent ions, promoted drug release. Dual drug (doxorubicin/verapamil
      or quinidine/verapamil)-loaded DS-SLNs were also formulated, which released both
      drugs without noticeable interference to each other. These studies have laid the
      foundation for a "one-bullet" dosage form that may provide convenient and
      effective delivery of multiple drug treatment of tumors.

PMID- 15236450
TI  - Permeability of tritiated water through human cervical and vaginal tissue.
AB  - The increased incidence of human immunodeficiency virus infection in women has
      identified an urgent need to develop a female-controlled method to prevent
      acquisition of human immunodeficiency virus and other sexually transmitted
      diseases. Women would apply the product intravaginally before intercourse.
      Development of such a product requires a better understanding of the permeability
      characteristics of the tissues with which such products would come into contact.
      However, limited studies have been performed in this area. In the present study,
      water permeability of fresh human cervical and vaginal tissue was evaluated. The
      average apparent permeability coefficient was found to be 8 x 10(-5) cm/s for
      fresh human cervical tissue and 7 x 10(-5) cm/s for fresh human vaginal tissue.
      Considering the lack of regularity in obtaining cervical and vaginal tissue from
      surgical specimens, additional tests were performed to evaluate the effect of
      freezing on tritiated water permeability. No statistically significant
      differences were observed in the permeability values obtained when comparing
      fresh versus frozen tissues.

PMID- 15236451
TI  - Improving the prediction of exceptionally poor tableting performance: an
      investigation into Hiestand's "special case".
AB  - The mechanical and flow properties of selected pharmaceutical powdered excipients
      and drug substances were evaluated to investigate their behavior as extremely
      poor tableting, or "special case," materials. The compaction stress, dynamic
      indentation hardness, and tensile strength of compacts compressed to 15% porosity
      and their powder's effective angle of internal friction were measured using the
      tableting indices technology and a simple shear cell, respectively. It has been
      previously demonstrated that compacts of special case materials exhibit a dynamic
      indentation hardness greater than the stress required to form the compact under
      slow compression conditions. In addition, new data suggest that special case
      materials also exhibit low compact dynamic indentation hardness, low compact
      tensile strength, and low powder effective angle of internal friction. These
      findings support the theory that the particles of such materials preferentially
      rearrange rather than deform under compressive conditions because bonding between
      them is weak. The added special case indicator measurements can be used to
      clearly identify exceptionally poor tableting powders during the selection of
      components for solid dosage formulations. Careful consideration of the data will
      provide guidance to the proper use of the bonding indices equations.

PMID- 15236452
TI  - Analysis of tablet compaction. I. Characterization of mechanical behavior of
      powder and powder/tooling friction.
AB  - In this first of two articles on the modeling of tablet compaction, the
      experimental inputs related to the constitutive model of the powder and the
      powder/tooling friction are determined. The continuum-based analysis of tableting
      makes use of an elasto-plastic model, which incorporates the elements of yield,
      plastic flow potential, and hardening, to describe the mechanical behavior of
      microcrystalline cellulose over the range of densities experienced during
      tableting. Specifically, a modified Drucker-Prager/cap plasticity model, which
      includes material parameters such as cohesion, internal friction, and hydrostatic
      yield pressure that evolve with the internal state variable relative density, was
      applied. Linear elasticity is assumed with the elastic parameters, Young's
      modulus, and Poisson's ratio dependent on the relative density. The calibration
      techniques were developed based on a series of simple mechanical tests including
      diametrical compression, simple compression, and die compaction using an
      instrumented die. The friction behavior is measured using an instrumented die and
      the experimental data are analyzed using the method of differential slices. The
      constitutive model and frictional properties are essential experimental inputs to
      the finite element-based model described in the companion article.

PMID- 15236453
TI  - Analysis of tablet compaction. II. Finite element analysis of density
      distributions in convex tablets.
AB  - A Drucker-Prager/cap constitutive model, where the elastic and plastic model
      parameters are expressed as a function of relative density (RD), was presented in
      a companion article together with experimental calibration procedures. Here, we
      examine the RD distribution in curved-faced tablets with special reference to the
      die wall lubrication conditions. The compaction of powders is examined using
      finite element analysis, which involves the following factors: constitutive
      behavior of powder, friction between powder and tooling, geometry of die and
      punches, sequence of punch motions, and initial conditions that result from die
      fill. The predictions of the model are validated using experimental RD maps. It
      is shown that different die wall lubrication conditions induce opposite density
      distribution trends in identical tablets (weight, height, and material). The
      importance of the internal tablet structure is illustrated with respect to break
      force, failure mode, and friability: it is demonstrated that for a given average
      tablet density the break force and failure mode are not unique. Also, tablet
      regions having lower density locally have higher propensity for damage. The
      applicability of finite element analysis for optimizations of formulation design,
      process development, tablet image, and tool design is discussed.

PMID- 15236454
TI  - Modification of buccal drug delivery following pretreatment with skin penetration
      enhancers.
AB  - The effect of the lipophilic skin penetration enhancers octisalate (OS), padimate
      O (PO), and Azone (AZ) on in vitro buccal permeability was assessed using
      caffeine (CAF), estradiol (E2), and triamcinolone acetonide (TAC) as model
      permeants. Buccal permeability was assessed in modified Ussing chambers, through
      both untreated porcine buccal mucosa and mucosa pretreated with an enhancer (5%
      w/v in 95% v/v ethanol) or ethanol alone. To ensure sink conditions were present,
      E2 permeability experiments were also performed with bovine serum albumin (BSA)
      4% in the receptor solution. Mucosa-buffer partition studies were performed to
      determine the effect of enhancer pretreatment on the log mucosa-buffer partition
      coefficient (logK) of E2 and TAC. CAF permeability was only increased following
      pretreatment with ethanol 95%. E2 buccal transport was not altered following OS
      pretreatment, but was reduced by 26.3% with PO pretreatment and 67.6% with AZ
      pretreatment. Similar results were obtained with BSA 4% in the receptor solution.
      The logK of E2 was increased 1.4-fold and 2.2-fold in PO- and AZ-pretreated
      tissues, respectively, suggesting that the reduction in flux caused by PO and AZ
      may have been due to enhanced E2 tissue retention. The effect of OS and PO on TAC
      permeability was no different to that of ethanol. However, AZ enhanced TAC
      permeability 4.1-fold and this was accompanied by a 2.4-fold increase in the logK
      of TAC.

PMID- 15236455
TI  - Surfactant-mediated dissolution: contributions of solubility enhancement and
      relatively low micelle diffusivity.
AB  - The objective of this study was to assess the contributions of surfactant
      mediated solubility and micellar diffusivity on the ability of surfactant to
      enhance drug dissolution. The following model was derived to predict the degree
      to which surfactants enhance griseofulvin dissolution: phi = 1 + (fm/ff).((D(D
      M)2/3)/(DD2/3)) where phi is the degree of surfactant-mediated dissolution
      enhancement, fm is the fraction of the drug in micelle, and ff is the fraction of
      free drug, and DD and D(D-M) are the diffusivities of free drug and drug-loaded
      micelles, respectively. The Wood apparatus was used to measure the dissolution of
      griseofluvin in the presence of the anionic surfactant sodium dodecyl sulfate
      (SDS), the cationic surfactant cetyl trimethyl ammonium bromide (CTAB), and the
      neutral surfactants Tween 80 and Cremophor EL. DD was estimated using the Levich
      equation. D(D-M) was measured using dynamic light scattering. Griseofulvin
      solubility was evaluated in SDS, CTAB, Tween 80, and Cremophor EL at the
      surfactant concentrations used in the dissolution studies. DD was 11.0 x 10(-6)
      cm2/s. D(D-M) was 1.29 x 10(-6) cm2/s, 0.956 x 10(-6) cm2/s, 0.569 x 10(-6)
      cm2/s, and 0.404 x 10(-6) cm2/s for griseofulvin-loaded micelles of SDS, CTAB,
      Tween 80, and Cremophor EL, respectively. At the highest surfactant
      concentrations studied, griseofulvin solubility increased 107-fold, 31-fold,
      fourfold, and threefold for SDS, CTAB, Tween 80, and Cremophor EL. Dissolution
      into SDS and CTAB were markedly enhanced, but only about one-third as much as
      solubility enhancement. Dissolution enhancement in the presence of SDS and CTAB
      were in excellent agreement with model predicted values, with prediction error
      less than 12%. The model predicted dissolution into Tween 80 and Cremophor EL to
      be minimally enhanced, as was observed, although the model underpredicted
      dissolution into these two neutral surfactants. The derived model predicted
      surfactant-mediated dissolution and reflects dissolution enhancement to be
      promoted by surfactant-enhanced solubility, but limited by the relatively slow
      diffusion of drug-loaded surfactant micelles.

PMID- 15236456
TI  - Nuclear magnetic resonance and molecular modeling analysis of the interaction of
      the antimalarial drugs artelinic acid and artesunic acid with beta-cyclodextrin.
AB  - The artemisinin derivatives artelinic acid and artesunic acid are members of a
      class of compounds that have shown promise for the treatment of multidrug
      resistant strains of Plasmodium falciparum. Unfortunately, these compounds
      exhibit poor solubility and stability in aqueous solution. The research presented
      herein was conducted to determine whether complexation of artelinic acid or
      artesunic acid with beta-cyclodextrin would result in complexes with increased
      aqueous solubility while retaining the potent antimalarial activity of these
      compounds. Preliminary complexation studies with natural beta-cyclodextrins were
      conducted as a proof of concept, with a primary focus on understanding the
      electrostatic interactions that stabilize the resulting complexes. Complex
      formation was monitored using UV spectroscopy. The structures of the resulting
      complexes were determined using multidimensional nuclear magnetic resonance
      spectroscopy (NMR) and molecular modeling. NMR results are most consistent for
      artelinic acid and beta-cyclodextrin forming complexes in a ratio of 2:1;
      however, the presence of 1:1, 2:2, and 3:1 complexes in solution cannot be
      excluded based on the experimental data collected. The NMR data also indicate
      selective insertion of artelinic acid into the hydrophobic cavity of the beta
      cyclodextrin via the primary face. NMR results indicate artesunic acid forms a
      similar complex with beta-cyclodextrin in a ratio of 1:1; again however, the
      presence of 1:1, 2:2, and 3:1 complexes in solution cannot be ruled out.

PMID- 15236457
TI  - Correlation of membrane order and dynamics derived from time-resolved
      fluorescence measurements with solute permeability.
AB  - The relevance of order and dynamics of phospholipid bilayer membranes as detected
      with fluorescent probe molecules embedded in the membranes for describing their
      permeability properties was studied. Order parameters (S) and rotational
      diffusion coefficients (Dperpendicular) of 1,6-diphenyl-1,3,5-hexatriene (DPH)
      and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in
      unilamellar vesicles were determined by time-resolved fluorescence spectroscopy.
      Vesicles consisting of combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylcholine, 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine, egg
      sphingomyelin and cholesterol were studied at 288, 298, and 308 degrees K.
      Permeability coefficients (P) of the model permeant D-[14C]mannitol were
      determined. A model was proposed for correlating P with both S and
      Dperpendicular, where S is linked to the average free surface area per lipid
      molecule and Dperpendicular reflects lipid thermal motion and, thus,
      redistribution rate of free surface area of the bilayer. P values ranging from
      0.9 to 12.4 x 10(-11) cm/s were well described by the model. This supports the
      notion that permeation depends on membrane structural and dynamic properties.
      While changes in both S and Dperpendicular, at relative significance varying with
      the situation, appeared responsible for the effect of lipid composition on
      permeability, the effect of temperature on P was related primarily to
      Dperpendicular. P correlated better with S and Dperpendicular obtained with TMA
      DPH rather than DPH. The location of the fluorescent probe molecules within the
      membranes is discussed as the cause for this difference.

PMID- 15236458
TI  - Exact kinetic analysis of passive transport across a polarized confluent MDCK
      cell monolayer modeled as a single barrier.
AB  - Knowledge of the passive permeability coefficient for new drugs is useful for
      estimating the fraction absorbed across the gastrointestinal tract. The commonly
      used approximate formula for the passive permeability coefficient is based on the
      initial rate of permeation across cell monolayers, requires measurement during
      the linear phase of permeation, and is not applicable when there is significant
      back flux of compound or mass balance problem. To develop a rigorous equation
      that can be used at any time point, i.e., that is valid outside of the linear
      phase, the mass action equations were integrated for a standard single barrier
      model of passive permeability. The simple analytical solution found also allows
      correction for both loss of drug (e.g., due to binding and/or hydrolysis) and
      sampling volume loss for multiple time point experiments. To test this equation,
      we measured the passive permeation of three well characterized drugs (amprenavir,
      quinidine, and loperamide) across confluent monolayers of MDCKII-hMDR1 cells. The
      potent P-glycoprotein inhibitor GF120918 was used to inhibit P-glycoprotein
      activity, so only passive permeability was determined. Dramatically different
      time-dependent behavior was observed for the three compounds, with loperamide
      showing significant loss of compound, and loperamide and quinidine causing plasma
      membrane modifications over time. The simple and exact equation for the
      permeability coefficient developed here works from start of transport to
      equilibrium, being valid when the commonly used approximate equation may not be.
      Thus, the exact equation is safer to use in any context, even for single time
      point estimates in high-throughput permeability assays.

PMID- 15236459
TI  - Figures of merit for the determination of the polymorphic purity of carbamazepine
      by infrared spectroscopy and multivariate calibration.
AB  - Polymorphism is an important property in the quality control of pharmaceutical
      products. In this regard, partial least squares regression and the net analytical
      signal were used to build and validate a multivariate calibration model using
      diffuse reflectance infrared spectroscopy in the region of 900-1100 cm(-1) for
      the determination of the polymorphic purity of carbamazepine. Physical mixtures
      of the polymorphs were made by weight, from 80 to 100% (w/w) form III mixed with
      form I. Figures of merit, such as sensitivity, analytical sensitivity,
      selectivity, confidence limits, precision (mean, repeatability, intermediate),
      accuracy, and signal-to-noise ratio were calculated. Feasible results were
      obtained with maximum absolute error of 2% and an average error of 0.53%,
      indicating that the proposed methodology can be used by the pharmaceutical
      industry as an alternative to the X-ray diffraction (United States
      Pharmacopoeiamethod).

PMID- 15236460
TI  - A novel method for determination of drug solubility in polymeric matrices.
AB  - Crystallization of drugs in metastable, supersaturated adhesive polymeric
      matrices in transdermal drug delivery devices can be avoided by determination of
      the solubility of the drug in the adhesive polymer. A novel method is described
      to determine the solubility of the drug in polymeric matrices. Unlike existing
      methods, this method does not require a long and uncertain experimental time, and
      is accurate. In this study, an easy and accurate method is presented for the
      determination of solubility of drugs in polymers based on the relationship
      between thermodynamic activity of drugs and steady-state flux. In particular, the
      steady-state flux from a reference saturated solution across a test membrane was
      compared to an experimentally determined relationship between the polymeric
      loading concentration and the observed steady-state fluxes. The validity of this
      method was demonstrated by comparing the results to microscopic observation of
      crystallization and the study of aged drug-loaded adhesives for lidocaine as a
      model drug and an acrylate pressure-sensitive adhesive as a model polymer. The
      solubility of lidocaine was 20.8 +/- 0.5% (w/w) in the acrylate polymer.

PMID- 15236461
TI  - Biodegradable polyphosphoester micelles for gene delivery.
AB  - A new biodegradable polyphosphoester, poly[[(cholesteryl oxocarbonylamido ethyl)
      methyl bis(ethylene) ammonium iodide] ethyl phosphate] (PCEP) was synthesized and
      investigated for gene delivery. Carrying a positive charge in its backbone and a
      lipophilic cholesterol structure in the side chain, PCEP self-assembled into
      micelles in aqueous buffer at room temperature with an average size of 60-100 nm.
      It could bind and protect plasmid DNA from nuclease digestion. Cell proliferation
      assay indicated a lower cytotoxicity for PCEP than for poly-L-lysine and
      Lipofectamine. The IC50 determined by the WST-1 assay was 69.8, 51.6, and 12.1
      microg/mL for PCEP, Lipofectamine, and poly-L-lysine, respectively. PCEP
      efficiently delivered DNA to several cell lines such as HEK293, Caco-2, and HeLa.
      The highest efficiency was achieved when PCEP/DNA complex was prepared in Opti
      MEM with a +/- charge ratio of 1.5-2. The transfection efficiency did not change
      significantly when the complex was used 3 days after preparation. The addition of
      chloroquine to the formulation increased transfection efficiency 10- to 50-fold
      compared to the complex alone. In vivo studies showed a luciferase expression by
      PCEP/DNA complexes in muscle increasing with time during 3 months, although the
      expression level was lower than that by direct injection of naked DNA. In
      addition to biodegradability and lower toxicity, the PCEP micelle carrier offers
      structural versatility. The backbone charge density and the side chain
      lipophilicity are two parameters that can be varied through copolymerization and
      monomer variation to optimize the transfection efficiency.

PMID- 15236462
TI  - A theoretical and experimental analysis of formulation and device parameters
      affecting solution MDI size distributions.
AB  - The influence of formulation and device configurations on the initial droplet and
      residual particle size distribution from solution MDIs was theoretically and
      experimentally examined. Aerodynamic size distribution tests were conducted to
      characterize the size distribution of the residual particles formed when a
      solution MDI is actuated. The measured size distributions were approximately log
      normally distributed, and did not show evidence of a secondary large particle
      mode. Theoretical relationships were developed to relate the residual particle
      size distribution to the initial size distribution of the atomized droplets. The
      residual particle size distribution was shown to be proportional to the
      nonvolatile concentration to the one-third power. Ethanol concentration,
      propellant type, valve size, and actuator orifice diameter were all shown to
      affect the initial droplet size distribution. Deposition of drug in the
      mouthpiece and USP inlet affect the measured size distribution during aerodynamic
      particle size measurements. Although there is a significant increase in the size
      of initial droplets as ethanol concentration increases, there is only a minor
      increase in the size of the residual particles measured when the USP Inlet is
      used due to size dependent deposition in the USP inlet and actuator mouthpiece.
      Vapor pressure was shown to explain only part of the differences in the size of
      the atomized droplets for various formulations. Theoretical and empirical
      equations were developed that make it possible to predict the residual particle
      size distribution for solution MDIs.

PMID- 15236463
TI  - Glycosylation patterns are sexually dimorphic throughout development of the
      olfactory system in Manduca sexta.
AB  - In the moth Manduca sexta, development of the adult olfactory system depends on
      complex interactions between olfactory receptor neurons in the antenna, antennal
      lobe neurons in the brain, and several classes of glial cells. As one approach to
      characterizing molecules that may play roles in these interactions, we used
      lectins to screen antennae and antennal lobes at different stages of adult
      development. We find that each of the major neural cell types has a distinct
      pattern of labeling by lectins. Effects of enzymatic and other treatments on
      lectin labeling lead us to conclude that the predominant lectin ligands are:
      glycosphingolipids and an O-linked, fucose-containing glycoprotein on axons of
      olfactory receptor neurons, O-linked glycoproteins on antennal-lobe neurons, and
      N-linked glycoproteins on all classes of glial cells in the primary olfactory
      pathway. Wheat germ agglutinin labels all olfactory axons uniformly during much
      of development, but labeling becomes restricted to the pheromone-responsive
      olfactory receptor neurons in the adult male. Succinylated WGA reveals
      differences in these axon classes earlier, as glomerului develop from
      protoglomeruli. The adult female displays a less pronounced difference in
      labeling of axons targeting ordinary and sexually dimorphic glomeruli.
      Differences in labeling of receptor axons targeted to ordinary and sexually
      dimorphic glomeruli may be correlated with differences in function or
      connectivity in different regions of the antennal lobe.

PMID- 15236464
TI  - Cocaine- and amphetamine-regulated transcript in catecholamine and
      noncatecholamine presympathetic vasomotor neurons of rat rostral ventrolateral
      medulla.
AB  - Presympathetic vasomotor adrenergic (C1) and nonadrenergic (non-C1) neurons in
      the rostral ventrolateral medulla (RVLM) provide the main excitatory drive to
      cardiovascular sympathetic preganglionic neurons in the spinal cord. C1 and non
      C1 neurons contain cocaine- and amphetamine-regulated transcript (CART),
      suggesting that CART may be a common marker for RVLM presympathetic neurons. To
      test this hypothesis, we first used double-immunofluorescence staining for CART
      and tyrosine hydroxylase (TH) to quantify CART-immunoreactive (-IR) catecholamine
      and noncatecholamine neurons in the C1 region. Next, we quantified the proportion
      of CART-IR RVLM neurons that expressed Fos in response to a hypotensive stimulus,
      using peroxidase immunohistochemistry for Fos and dual immunofluorescence for
      CART and TH. Finally, we fluorescently detected CART immunoreactivity in
      electrophysiologically identified, juxtacellularly labeled RVLM presympathetic
      neurons. In the RVLM, 97% of TH-IR neurons were CART-IR, and 74% of CART-IR
      neurons were TH-IR. Nitroprusside infusion significantly increased the number of
      Fos-IR RVLM neurons compared with saline controls. In nitroprusside-treated rats,
      virtually all Fos/TH neurons in the RVLM were immunoreactive for CART (98% +/-
      1.3%, SD; n = 7), whereas 29% +/- 8.3% of CART-positive, TH-negative neurons
      showed Fos immunoreactivity. Six fast (2.8-5.8 m/second, noncatecholamine)-, two
      intermediate (2.1 and 2.2 m/second)-, and five slow (<1 m/second, catecholamine)
      conducting RVLM presympathetic vasomotor neurons were juxtacellularly labeled.
      After fluorescent detection of CART and biotinamide, all 13 neurons were found to
      be CART-IR. These results suggest that, in rat RVLM, all catecholamine and
      noncatecholamine presympathetic vasomotor neurons contain CART.

PMID- 15236465
TI  - Analysis of the cellular expression pattern of beta-CGRP in alpha-CGRP-deficient
      mice.
AB  - In this study we compared the alpha-calcitonin gene-related peptide (alphaCGRP)
      and betaCGRP expression patterns in wild-type and knockout mice by using
      quantitative reverse transcriptase polymerase chain reaction and
      immunohistochemistry. In dorsal root ganglia and spinal cord of wild-type
      animals, alphaCGRP mRNA was about two times more abundant than betaCGRP mRNA. The
      betaCGRP mRNA was the only isoform expressed in the intestine. In alphaCGRP
      knockout mice, we found no change in betaCGRP mRNA levels in dorsal root ganglia
      and spinal cord compared with wild-type controls, but a twofold decrease in the
      intestine. CGRP immunoreactivity (IR) was detected in many small and some large
      neurons in the dorsal root ganglia, was found in sensory fibers and motor neurons
      in the spinal cord, and labeled neuromuscular junctions in wild-type mice. In the
      dorsal root ganglia of alphaCGRP knockout mice, punctate betaCGRP-IR again was
      predominantly found in small neurons. In the spinal cord, betaCGRP-IR fibers were
      localized to the outermost layer of the dorsal horn. IR was found in the cell
      bodies of motor neurons, but it was undetectable in neuromuscular junctions. In
      the intestine, CGRP-IR was localized to neurons of the myenteric plexus and to
      fibers in the mucosal folds, with similar staining intensity in both wild-type
      and knockout mice. Finally, CGRP-IR was undetectable in preganglionic fibers and
      postganglionic sympathetic neurons in mice from both genotypes. Our results
      indicate that alphaCGRP and betaCGRP are variably coexpressed in different
      functional aspects of the mouse nervous system. This pattern suggests distinct
      roles for betaCGRP in pain, neuromuscular, and gastrointestinal systems.

PMID- 15236467
TI  - An electron microscope immunocytochemical study of GABA(B) R2 receptors in the
      monkey basal ganglia: a comparative analysis with GABA(B) R1 receptor
      distribution.
AB  - Functional gamma-aminobutyric acid (GABA)(B) receptors are heterodimers made up
      of GABA(B) R1 and GABA(B) R2 subunits. The subcellular localization of GABA(B) R2
      receptors remains poorly known in the central nervous system. Therefore, we
      performed an ultrastructural analysis of the localization of GABA(B) R2 receptor
      immunoreactivity in the monkey basal ganglia. Furthermore, to characterize better
      the neuronal sites at which GABA(B) R1 and GABA(B) R2 may interact to form
      functional receptors, we compared the relative distribution of immunoreactivity
      of the two GABA(B) receptors in various basal ganglia nuclei. Light to moderate
      GABA(B) R2 immunoreactivity was found in cell bodies and neuropil elements in all
      basal ganglia nuclei. At the electron microscope level, GABA(B) R2
      immunoreactivity was commonly expressed postsynaptically, although immunoreactive
      preterminal axonal segments were also frequently encountered, particularly in the
      globus pallidus and substantia nigra, where they accounted for the third of the
      total number of GABA(B) R2-containing elements. A few labeled terminals that
      displayed the ultrastructural features of glutamatergic boutons were occasionally
      found in most basal ganglia nuclei, except for the subthalamic nucleus, which was
      devoid of GABA(B) R2-immunoreactive boutons. The relative distribution of GABA(B)
      R2 immunoreactivity in the monkey basal ganglia was largely consistent with that
      of GABA(B) R1, but some exceptions were found, most noticeably in the globus
      pallidus and substantia nigra, which contained a significantly larger proportion
      of presynaptic elements labeled for GABA(B) R1 than GABA(B) R2. These findings
      suggest the possible coexistence and heterodimerization of GABA(B) R1 and GABA(B)
      R2 at various pre- and postsynaptic sites, but also raise the possibility that
      the formation of functional GABA(B) receptors in specific compartments of basal
      ganglia neurons relies on mechanisms other than GABA(B) R1/R2 heterodimerization.

PMID- 15236468
TI  - Noradrenergic innervation of the developing and mature septal area of the rat.
AB  - The noradrenergic innervation of the developing and mature septal area of the rat
      was examined with light and electron microscopic immunocytochemistry using an
      antibody against dopamine-beta-hydroxylase. At birth, a small number of
      relatively thick noradrenergic fibers were found to innervate the lateral septum
      (mainly its intermediate part) and the nuclei of the vertical and horizontal
      limbs of the diagonal band of Broca. By postnatal day 7, a substantial increase
      in their density was observed. At this age some labeled fibers left the medial
      forebrain bundle and invaded the nucleus of the horizontal limb of the diagonal
      band. These fibers then ran in a ventrodorsal direction and innervated the
      nucleus of the vertical limb before entering the medial septum. Immunoreactive
      fibers were finer and more varicose than at birth. In the subsequent 2 weeks, the
      density of labeled fibers in the septal area was further increased. By postnatal
      day 21, the distribution pattern and density of the noradrenergic innervation
      appeared similar to the adult. In the adult, noradrenergic fibers exhibited more
      varicosities than in younger rats. Electron microscopic analysis revealed a low
      proportion (peaked at P7) of noradrenergic varicosities engaged in synaptic
      contacts throughout development. The overwhelming majority of these synapses were
      symmetrical, predominantly with small or medium-sized dendrites. The present
      findings provide the morphological basis for the functional interactions between
      noradrenergic afferents and neuronal elements in the septal area. The low
      proportion of synaptic contacts found in this study suggests that noradrenaline
      may exert its action in the septal area mainly through transmission by diffusion
      (volume transmission), as has been suggested for other areas of the developing
      and adult brain.

PMID- 15236466
TI  - Differential expression of glutamate receptors in avian neural pathways for
      learned vocalization.
AB  - Learned vocalization, the substrate for human language, is a rare trait. It is
      found in three distantly related groups of birds-parrots, hummingbirds, and
      songbirds. These three groups contain cerebral vocal nuclei for learned
      vocalization not found in their more closely related vocal nonlearning relatives.
      Here, we cloned 21 receptor subunits/subtypes of all four glutamate receptor
      families (AMPA, kainate, NMDA, and metabotropic) and examined their expression in
      vocal nuclei of songbirds. We also examined expression of a subset of these
      receptors in vocal nuclei of hummingbirds and parrots, as well as in the brains
      of dove species as examples of close vocal nonlearning relatives. Among the 21
      subunits/subtypes, 19 showed higher and/or lower prominent differential
      expression in songbird vocal nuclei relative to the surrounding brain
      subdivisions in which the vocal nuclei are located. This included relatively
      lower levels of all four AMPA subunits in lMAN, strikingly higher levels of the
      kainite subunit GluR5 in the robust nucleus of the arcopallium (RA), higher and
      lower levels respectively of the NMDA subunits NR2A and NR2B in most vocal nuclei
      and lower levels of the metabotropic group I subtypes (mGluR1 and -5) in most
      vocal nuclei and the group II subtype (mGluR2), showing a unique expression
      pattern of very low levels in RA and very high levels in HVC. The splice variants
      of AMPA subunits showed further differential expression in vocal nuclei. Some of
      the receptor subunits/subtypes also showed differential expression in hummingbird
      and parrot vocal nuclei. The magnitude of differential expression in vocal nuclei
      of all three vocal learners was unique compared with the smaller magnitude of
      differences found for nonvocal areas of vocal learners and vocal nonlearners. Our
      results suggest that evolution of vocal learning was accompanied by differential
      expression of a conserved gene family for synaptic transmission and plasticity in
      vocal nuclei. They also suggest that neural activity and signal transduction in
      vocal nuclei of vocal learners will be different relative to the surrounding
      brain areas.

PMID- 15236469
TI  - Activin mRNA induced during amygdala kindling shows a spatiotemporal progression
      that tracks the spread of seizures.
AB  - The progressive development of seizures in rats by amygdala kindling, which
      models temporal lobe epilepsy, allows the study of molecular regulators of
      enduring synaptic changes. Neurotrophins play important roles in synaptic
      plasticity and neuroprotection. Activin, a member of the transforming growth
      factor-beta superfamily of growth and differentiation factors, has recently been
      added to the list of candidate synaptic regulators. We mapped the induction of
      activin betaA mRNA in amygdala and cortex at several stages of seizure
      development. Strong induction, measured 2 hours after the first stage 2 (partial)
      seizure, appeared in neurons of the ipsilateral amygdala (confined to the
      lateral, basal, and posterior cortical nuclei) and insular, piriform, orbital,
      and infralimbic cortices. Activin betaA mRNA induction, after the first stage 5
      (generalized) seizure, had spread to the contralateral amygdala (same nuclear
      distribution) and cortex, and the induced labeling covered much of the convexity
      of neocortex as well as piriform, perirhinal, and entorhinal cortices in a nearly
      bilaterally symmetrical pattern. This pattern had filled in by the sixth stage 5
      seizure. Induced labeling in cortical neurons was confined mainly to layer II. A
      similar temporal and spatial pattern of increased mRNA expression of brain
      derived neurotrophic factor (BDNF) was found in the amygdala and cortex. Activin
      betaA and BDNF expression patterns were similar at 1, 2, and 6 hours after the
      last seizure, subsiding at 24 hours; in contrast, c-fos mRNA induction appeared
      only at 1 hour throughout cortex and then subsided. In double-label studies,
      activin betaA mRNA-positive neurons were also BDNF mRNA positive, and they did
      not colocalize with GAD67 mRNA (a marker of gamma-aminobutyric acidergic
      neurons). The data suggest that activin and BDNF transcriptional activities
      accurately mark excitatory neurons participating in seizure-induced synaptic
      alterations and may contribute to the enduring changes that underlie the kindled
      state.

PMID- 15236471
TI  - Characteristics of photosynthesis in rice plants transformed with an antisense
      Rubisco activase gene.
AB  - Transgenic rice plants with an antisense gene inserted via Agrobacterium
      tumefaciens were used to explore the impact of the reduction of Rubisco activase
      (RCA) on Rubisco and photosynthesis. In this study, transformants containing 15%
      to 35% wild type Rubisco activase were selected, which could survive in ambient
      CO2 concentration but grew slowly compared with wild type controls. Gas exchange
      measurements indicated that the rate of photosynthesis decreased significantly,
      while stomatal conductance and transpiration rate did not change; and that the
      intercellular CO2 concentration even increased. Rubisco determination showed that
      these plants had approximately twice as much Rubisco as the wild types, although
      they showed 70% lower rate of photosynthesis, which was likely an acclimation
      response to the reduction in Rubsico activase and/or the reduction in
      carbamylation.

PMID- 15236470
TI  - OFF-cholinergic-pathway-selective localization of P2X2 purinoceptors in the mouse
      retina.
AB  - It is known that, in the retina, extracellular adenosine triphosphate (ATP)
      inhibits acetylcholine (ACh) release from cholinergic neurons, but the types of
      purinoceptors on cholinergic neurons have not been examined. In the present work,
      we immunohistochemically examined the distribution of the purinoceptors P2X1,
      P2X2, P2X4, and P2X7 in relation to the cholinergic system of the retina in wild
      type mice and transgenic mice expressing green fluorescent protein (GFP).
      Immunoreactivity for P2X2 was very strong in sublamina a of the inner plexiform
      layer but very weak in sublamina b of the inner plexiform layer of the retina.
      Immunoreactivity for P2X2 was colocalized with that for choline acetyltransferase
      (ChAT). When transgenic mice were treated with the immunotoxin-mediated cell
      targeting technology to ablate cholinergic amacrine cells selectively,
      immunoreactivity for P2X2 and the signals for GFP disappeared in parallel and
      selectively in the OFF pathway. The distribution of immunoreactivity for P2X1,
      P2X4, and P2X7 differed from that of ChAT immunoreactivity. The selective
      distribution of P2X2 purinergic receptors in OFF-type cholinergic amacrine cells
      indicates that the P2X2 purinergic signaling systems in the ON and OFF pathways
      of the inner plexiform layer of the mouse retina are functionally different. The
      distribution of P2X2 purinoceptors may be responsible for the selective
      regulation of ACh release in the OFF pathway.

PMID- 15236472
TI  - Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with
      HPLC/ESI-MS for drug candidate screening.
AB  - A method of screening assay is demonstrated. The approach is based on the
      affinity of antitumor candidates for topoisomerases. In this method, antitumor
      candidates are fished out using topoisomerases as targets. Traditional analysis
      of complex compounds typically encounters signal suppression due to the
      relatively low concentrations, but enzyme-affinity screening for the active
      compounds can effectively concentrate the desired analysts into a small volume of
      high concentration. Active compounds are separated from non-affinity compounds by
      ultrafiltration. The molecules-enzymes complexes that are retained on the filter
      are subsequently separated by acidification to obtain the topoisomerases-affinity
      compounds for analysis on High Performance Liquid Chromatography coupled with
      electrospray ionization mass spectrometric detection (ESI-MS). This enzyme
      affinity based screening assay provides a highly specific and efficient method
      that can directly screen, identify, and acquire drug candidates thus improving
      the accuracy and speed of high-throughput screening activities.

PMID- 15236473
TI  - Water-soluble UV curable urethane methyl acrylate coating: preparation and
      properties.
AB  - Two kinds of water-soluble and ultraviolet (UV) curable oligomers were
      synthesized and characterized. The oligomers were evaluated as resins for water
      based UV curable coating. The rheology of the two oligomers' aqueous solutions
      was investigated in terms of solid fraction, pH dependence, and temperature
      dependence. The solutions were found to be Newtonian fluid showing rather low
      viscosity even at high solid fraction of 0.55. The drying process of the coatings
      and the properties of the cured coatings were studied by comparing them with
      water-dispersed UV-curable polyurethane methyl acrylate. It was evident that the
      water-soluble coating dried more slowly; and that the overall properties were
      inferior to those of the water-dispersed coating.

PMID- 15236474
TI  - Study on the distribution of active centers in novel low Ti-loading MgCl2
      supported Ziegler-Natta catalyst.
AB  - Novel MgCl2-supported Ziegler-Natta (Z-N) catalysts prepared using a new one-pot
      ball milling method can effectively control the amounts of Ti-loading in the
      catalysts. Complex GPC data on polypropylene synthesized by these novel catalysts
      were analyzed using the method of fitting the molecular weight distribution (MWD)
      curves with a multiple Flory-Schulz function. It was found that multiple active
      centers exist in these novel catalysts. Detailed study of the effects of the Ti
      loadings in the catalysts on the distribution of the active centers showed that
      the Ti-loadings in the novel MgCl2-supported Z-N catalysts might affect the
      proportion of each type of active centers; and might be the main factor
      responsible for the effect of the Ti-loadings on the microstructure, the
      molecular weight and molecular weight distribution width of the resultant
      polymer, the catalytic activity and polymerization kinetics.

PMID- 15236475
TI  - Study on Bombyx mori silk treated by oxygen plasma.
AB  - Study of the morphology, aggregation structure and properties of Bombyx mori silk
      treated by low temperature oxygen plasma showed that slight flutes appeared on
      the surface of Bombyx mori silk fiber and that its surface structure changed
      after plasma treatment. The conformation also changed and crystalline degree
      decreased. The stannic filling rate of treated fiber was improved. Because of
      etching, the weight of the fiber decreased but the breaking strength changed
      little after short-time treatment.

PMID- 15236476
TI  - Charge dynamic characteristics in corona-charged polytetrafluoroethylene film
      electrets.
AB  - In this work, the charge dynamics characteristics of injection, transport and
      decay in porous and non-porous polytetrafluoroethylene (PTFE) film electrets were
      investigated by means of corona charging, isothermal and thermal stimulating
      surface-potential decay measurements. The results showed that the initial surface
      potential, whether positively or negatively charging, is much higher in non
      porous PTFE than in porous PTFE. For porous film the value of initial surface
      potentials increases with increase of film thickness. Higher charging temperature
      can remarkably improve charge stability. The charge dynamics are correlated to
      materials microstructure according to their scanning electron micrographs. For
      non-porous PTFE films, polarizability change of C-F bonds is the main origin of
      electret charges; but for porous PTFE film a large number of bulk and interface
      type traps are expected because of the greater area of interface and higher
      crystallinity.

PMID- 15236477
TI  - Gel time of calcium acrylate grouting material.
AB  - Calcium acrylate is a polymerized grout, and can polymerize in an aqueous
      solution. The polymerization reaction utilizes ammonium persulfate as a catalyst
      and sodium thiosulfate as the activator. Based on the theory of reaction
      kinetics, this study on the relation between gel time and concentration of
      activator and catalyst showed that gel time of calcium acrylate is inversely
      proportional to activator and catalyst concentration. A formula of gel time is
      proposed, and an example is provided to verify the proposed formula.

PMID- 15236478
TI  - Theoretical study of NO adsorbed on the surface of TiO2(110) cluster model.
AB  - The chemisorption properties of N18O adsorption on TiO2(110) surface were
      investigated by experimental and theoretical methods. The results of temperature
      programmed desorption (TPD) indicated that the temperatures of the three
      desorption peaks of the main N2 molecules were at (low) temperature of 230 K, 450
      K, and (high) temperature of 980 K. This meant that N18O decomposed and
      recombined during the process of N2 desorption after N18O was exposed. Analysis
      of the stable combination and orbital theory calculation of the surface reaction
      of NO adsorption on the TiO2(110) cluster model showed that there was clear
      preference for the Ti-NO orientation.

PMID- 15236479
TI  - Water-dispersed bone morphogenetic protein nanospheres prepared by co
      precipitation method.
AB  - A modified complex coacervation-co-precipitation method was used to prepare bone
      morphogenetic protein (BMP)-loaded nanospheres. Three natural polymers were used
      as packing materials to obtain nanoscale delivery device for BMP, in the presence
      of phosphatidylcholine functioning as stabilizer. Positively charged
      polysaccharide, N,N-diethylaminoethyl dextran (DEAE-dextran) tended to form
      stable, uniform and smaller size particles carrying BMP. Negatively charged
      bovine serum albumin (BSA) induced precipitation of the produced BMP particles
      due to its weak interaction with BMP molecules, although it produced nanosized
      BMP spheres. While collagen, a weakly positively charged protein shaped larger
      particles due to the strong interaction among themselves. A mechanism of co
      precipitation process was also deduced to depict the formation of stable
      nanospheres.

PMID- 15236480
TI  - Study on properties of residue-residue contacts in protein.
AB  - Residue-residue contacts are very important in forming protein structure. In this
      work, we calculated the average probability of residue-residue contacts in 470
      globular proteins and analyzed the distribution of contacts in the different
      interval of residues using Contacts of Structural Units (CSU) and Structural
      Classification (SCOP) software. It was found that the relationship between the
      average probability PL and the residue distance L for four structural classes of
      proteins could be expressed as lgPL=a+b x L, where a and b are coefficients. We
      also discussed the connection between two aspects of proteins which have equal
      array residue number and found that the distribution probability was stable (or
      un-stable) if the proteins had the same (or different) compact (for example
      synthase) in the same structural class.

PMID- 15236481
TI  - Investigation of compaction and sintering behavior of SiC powder after ultra-fine
      treatment.
AB  - Silicon carbide ceramics were prepared with SiC powder treated by the fluidized
      bed opposed jet mill as raw materials, and the effects of the ultra-fine
      treatment mechanism on the compaction and sintering behavior of SiC ceramics were
      investigated. The results showed that the compacts had higher density and
      microstructure homogeneity when the sintering temperature of the compact was
      decreased; and that the surface microstructure, densification and mechanical
      properties of the sintered body could be ameliorated obviously.

PMID- 15236482
TI  - Cleaner and convenient preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2
      methyl-phenol.
AB  - Environmental concerns have highlighted the need of cleaner technologies. A
      cleaner, convenient and selective technology has been developed for the
      preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (DPMP) from 2
      methyl-benzene-1,3-diol in water as solvent. The isolated yield of DPMP is up to
      86% in good selectivity. The product structure was characterized by conventional
      methods, 1H-NMR and MS. This technology belongs to the modern concept of
      environmentally friendly low wastes or non-wastes technology (LWNWT).

PMID- 15236483
TI  - Neogene coupling between Kuqa Basin and Southern Tien Shan Orogen, Northwestern
      China.
AB  - Based on the sedimentary and subsiding features of Kuqa foreland basin, this
      paper presents the following characteristics of Neogene coupling relationship
      between Kuqa Basin and Southern Tien Shan Orogen, Northwestern China: (1) The
      Southern Tien Shan Orogen underwent Neogene uplifting of 4 km in height and the
      Kuqa Basin underwent Neogene subsidence of 4-6 km in depth accordingly beginning
      in 25 Ma; (2) The Southern Tien Shan Orogen moved continuously toward the Kuqa
      Basin, with largest structural shortening rate of greater than 53.7%, and the
      north boundary of the Kuqa Basin retreated continuously southward accordingly
      since the Miocene; (3) There are two subsidence centers with high subsiding rates
      and large subsiding extent, located in the eastern and western Kuqa Basin
      respectively, with the subsiding maximizing in the deposition period of Kuqa
      Formation.

PMID- 15236484
TI  - Hydrocarbon charging histories of the Ordovician reservoir in the Tahe oil field,
      Tarim Basin, China.
AB  - The Ordovician reservoir of the Tahe oil field went through many tectonic
      reconstructions, and was characterized by multiple hydrocarbon chargings. The aim
      of this study was to unravel the complex charging histories. Systematic analysis
      of fluid inclusions was employed to complete the investigation. Fluorescence
      observation of oil inclusions under UV light, and microthermometry of both oil
      and aqueous inclusions in 105 core samples taken from the Ordovician reservoir
      indicated that the Ordovician reservoir underwent four oil chargings and a gas
      charging. The hydrocarbon chargings occurred at the late Hercynian, the Indo
      Sinian and Yanshan, the early Himalaya, the middle Himalaya, and the late
      Himalaya, respectively. The critical hydrocarbon charging time was at the late
      Hercynian.

PMID- 15236485
TI  - Petrology, geochemistry and geodynamics of basic granulite from the Altay area,
      North Xinjiang, China.
AB  - The basic granulite of the Altay orogenic belt occurs as tectonic lens in the
      Devonian medium- to lower-grade metamorphic beds through fault contact. The Altay
      granulite (AG) is an amphibole plagioclase two-pyroxene granulite and is mainly
      composed of two pyroxenes, plagioclase, amphibole and biotite. Its melano
      minerals are rich in Mg/(Mg+Fe2+), and its amphibole and biotite are rich in
      TiO2. The AG is rich in Mg/(Mg+Fe2+), Al2O3 and depletion of U, Th and Rb
      contents. The AG has moderate SigmaREE and LREE-enriched with weak positive Eu
      anomaly. The AG shows island-arc pattern with negative Nb, P and Ti anomalies,
      reflecting that formation of the AG may be associated with subduction.
      Geochemical and mineral composition data reflect that the protolith of the AG is
      calc-alkaline basalt and formed by granulite facies metamorphism having peak P-T
      conditions of 750 degrees C-780 degrees C and 0.6-0.7 Gpa. The AG formation
      underwent two stages was suggested. In the early stage of oceanic crustal
      subduction, calc-alkaline basalt with island-arc environment underwent granulite
      facies metamorphism to form the AG in deep crust, and in the late stage, the AG
      was thrust into the upper crust.

PMID- 15236486
TI  - Corneal relaxing incision combined with phacoemulsification and IOL implantation.
AB  - OBJECTIVE: To analyze the effectiveness and safety of corneal relaxing incisions
      (CRI) in correcting keratometric astigmatism during cataract surgery. METHODS: A
      prospective study of two groups: control group and treatment group. A treatment
      group included 25 eyes of 25 patients who had combined clear corneal
      phacoemulsification, IOL implantation and CRI. A control group included 25 eyes
      of 25 patients who had clear corneal phacoemulsification and IOL implantation.
      Postoperative keratometric astigmatism was measured at 1 week, 1 month, 3 months
      and 6 months. RESULTS: CRI significantly decreased keratometric astigmatism in
      patients with preexisting astigmatism compared with astigmatic changes in the
      control group. In eyes with CRI, the mean keratometric astigmatism was 0.29+/
      0.17 D (range 0 to 0.5 D) at 1 week, 0.41+/-0.21 D (range 0 to 0.82 D) at 1
      month, respectively reduced by 2.42 D and 2.30 D at 1 week and 1 month
      postoperatively (P=0.000, P=0.000), and postoperative astigmatism was stable
      until 6 months follow-up. The keratometric astigmatism of all patients decreased
      to less than 1.00 D postoperatively. CONCLUSIONS: CRI is a practical, simple,
      safe and effective method to reduce preexisting astigmatism during cataract
      surgery. A modified nomogram is proposed. The long-term effect of CRI should be
      investigated.

PMID- 15236487
TI  - Investigation on apoptosis of neuronal cells induced by Amyloid beta-Protein.
AB  - OBJECTIVE: To construct a PC12 cell strain with neuronal differentiation, and
      observe the apoptosis and proliferation activity effects induced these cells by
      Amyloid beta-Protein (Abeta-43). METHODS: 1) PC12 cells in logarithmic growth
      phase were subcultured for 24 h. After the culture fluid was changed, the cells
      were treated with Rat-beta-NGF and cultured for 9 days. 2) Neuronal
      differentiation of PC12 cells in logarithmic growth phase were divided into four
      groups: control group (0), experimental group (1), experimental group (2) and
      experimental group (3). The concentrations of Abeta in the four groups were 0
      micromol/L, 1.25 micromol/L, 2.5 micromol/L and 5 micromol/L, respectively. The
      cells were harvested at 24, 48 and 72 h later and stained with AnnexinV-FITC/PI
      after centrifugation and washing. Then flow cytometry was conducted to examine
      the apoptosis percentage. 3) NGF-induced PC12 cells were selected and Abeta with
      different concentrations was added. The final concentrations of Abeta were 0
      micromol/L, 1.25 micromol/L, 2.5 micromol/L and 5 micromol/L, respectively. After
      the cells were incubated in an atmosphere of 5% CO2 at 37 degrees C in an
      incubator for 72 h, the OD values were examined. RESULTS: 1) Neuronal
      differentiated PC12 cell lines were successfully established. 2) Flow cytometric
      examination indicated that Abeta (1.25, 2.5, and 5.0 micromol/L) could
      effectively induce apoptosis of neuronal-differentiated cells at the 24 h, 48 h
      and 72 h time points. 3) Abeta (0-5.00 micromol/L) had no obvious effect on
      proliferation or restraining of the neuronal differentiation of the PC12 cells
      after a 72 h interacting process. CONCLUSION: This investigation revealed
      successful neuronal differentiation of the PC12 cell strain. The induction of
      apoptosis of the neurocytes by various concentrations of Abeta was observed and
      the influence of Abeta on induced proliferation of PC12 cells by Rat-beta-NGF was
      revealed. This study may provide basis for future research on the molecular cure
      of AD and interdiction of AD evolution.

PMID- 15236489
TI  - Effect of lead exposure on the immune function of lymphocytes and erythrocytes in
      preschool children.
AB  - OBJECTIVE: To investigate the influence of lead exposure on the immune function
      of lymphocytes and erythrocytes in preschool children. MATERIALS AND METHODS: A
      group of 217 children three to six years of age from a rural area were given a
      thorough physical examination and the concentration of lead in blood samples
      taken from each subject was determined. The indices of lymphocyte immunity
      (CD+3CD+4, CD+3CD+8, CD+4CD+8, CD-3CD+19) and erythrocyte immunity (RBC-C3b, RBC
      IC, RFER, RFIR, CD35 and its average fluorescence intensity) of 40 children with
      blood lead levels above 0.483 micromol/L were measured and compared with a
      control group. RESULTS: The blood lead levels of the 217 children ranged from
      0.11 micromol/L to 2.11 micromol/L. The CD+3CD+4 and CD+4CD+8 cells were lower
      (P<0.01) and the CD+3CD+8 cells were higher in the lead-poisoned subjects than
      those in the control group (P<0.05). CD+3 and CD-3CD+19 did not show significant
      differences. Although the RBC-C3b rosette forming rate was lower and the RBC-IC
      rosette forming rate was higher in the lead-poisoned group, this difference could
      not be shown to be statistically significant (P>0.05). RFIR was found to be lower
      in the lead-poisoned group (P<0.01). Compared with the control group, the
      positive rate of CD35 was not found to be significantly different in a group of
      25 lead-poisoned children (P>0.05), while the average fluorescence intensity was
      lower in the lead-poisoned group (P<0.05). CONCLUSION: Lead exposure can result
      in impaired immune function of T lymphocytes and erythrocytes in preschool
      children.

PMID- 15236488
TI  - VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced
      pulmonary hypertension.
AB  - OBJECTIVE: To investigate the evolution of pulmonary hypertension, the
      pathological changes of pulmonary arteries, and the expression of VEGFmRNA and
      eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with
      intratracheal bleomycin (BLM). METHODS: Immature rabbits were divided into
      control and BLM group. Two and four weeks after intratracheal normal saline or
      BLM injection, 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: Two and four weeks after
      intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52%
      in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the
      cavity in middle and small pulmonary arteries became narrow; the Thickness Index
      (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4 weeks;
      the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and
      43%, 51% in 4 weeks. There was no significant difference between 2 weeks and 4
      weeks BLM groups. CONCLUSION: The pulmonary artery pressure was elevated, the
      thickness of wall increased and the cavity became narrow in middle and small
      pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in
      pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks
      and 4 weeks of intratracheal 4 U/kg BLM injection.

PMID- 15236490
TI  - Off-pump coronary artery bypass grafting versus on-pump coronary artery bypass
      grafting: which is better in patients with chronic obstructive pulmonary disease?
AB  - To evaluate the clinic outcome of off-pump coronary bypass grafting (OPCABG) of
      patients with coronary heart disease and chronic obstructive pulmonary disease,
      we collected and analyzed 1998-2002 data on 28 patients with these two diseases
      who had received off-pump coronary bypass operation in our hospital, and compared
      with data on those who also had the same two diseases but received on-pump
      coronary artery bypass at same time. There were no operation-related death; one
      died of respiratory failure 14 days after operation while staying in hospital;
      there were more respiratory complications in the conventional coronary artery
      bypass grafting group (CCABG) than in the OPCABG group; and the PaO2/FiO2 in the
      CCABG group was higher than that in the OPCABG group during operation because of
      CPB, but lower than that in the OPCABG group 6-12 hours after operation. OPCABG
      seemed more suitable than CCABG for coronary artery disease patients with chronic
      obstructive pulmonary disease due to less damage to their oxygen-exchange
      capability and the fewer respiratory complications.

PMID- 15236491
TI  - Occupational asthma diagnosis in workers exposed to organic dust.
AB  - The clinical evaluation of newly developed asthma in an adult should always
      include consideration of his occupational environment, since an abundance of
      different exposures, which are known causes of asthma, occur in workplaces. Two
      types of occupational asthma (OA) are distinguished, by whether they appear after
      a latency period: 1)Immunological OA, characterised by a latency period, caused
      by high and low-molecular-weight agents, with or without an IgE mechanism 2) Non
      immunological, i.e. irritant induced asthma. The first step of the clinical
      evaluation is to confirm a diagnosis of asthma. Second step is to find out if
      there is a temporo-spatial distribution of symptoms and lung function that are
      indicative of OA. Third step is to determine if the disease at hand is an IgE or
      a non-IgE mediated disease. Last step is a challenge test that can be either
      unspecific, in order to assess the responsiveness of the lung, or specific
      challenge test, especially for the non-IgE mediated OA. The depth of clinical
      evaluation may vary from a situation in which a classical history confirms the
      clinical symptoms in e.g. a baker with confirmed allergy towards well-known
      allergens and a characteristic pattern in serial measurements of lung function,
      to more elaborate investigations in a situation with no or unknown allergen. In
      the latter situation, a specific challenge test might be necessary in order to
      find the offending agent. Finally, challenge tests are important in order to
      distinguish a causal relation from unspecific hyperresponsiveness in persons with
      pre-existing asthma. In these situations, extended sick leave and challenge tests
      can be the only way to find the answer.

PMID- 15236492
TI  - Risk of exposure to Legionella in dental practice.
AB  - Aerosols generated in dental operations are a source of exposure to
      microorganisms proliferated within dental unit waterlines (DUWL) biofilm. It has
      been suggested that presence of Legionella species in these aerosols may
      contribute to potential health hazards for dental staff and patients. The article
      attempts to provide a brief overview of the current knowledge about Legionella,
      its prevalence in DUWL, immunological reactions of the dentists and concepts for
      prophylaxis of Legionella in dentists' work place.

PMID- 15236493
TI  - Respiratory symptoms and peak expiratory flow rates among furniture-decoration
      students.
AB  - This study was designed to evaluate the effects of furniture production, mainly
      including fir tree (aberia mulleriana), on respiratory health of young workers
      and to compare the results with those obtained from previous studies. Sixty-four
      furniture-decoration students (57 males and 7 females) and 62 controls (54 male,
      8 female) from different departments in the same school were included into the
      study. All participants were assessed with a questionnaire (concerning history of
      occupational exposure, work-related respiratory and other symptoms, smoking
      history, previous asthma history), full physical examination, spirometric
      evaluation and chest radiograph. Participants then performed serial monitoring of
      peak expiratory flow rates (PEFR) at work and away from work within a month. Mean
      age of students was 20.9 +/- 3.7 years, 20.5 +/- 2.6 years in controls. There was
      no difference between study and control groups with regard to age, gender,
      smoking status and previous asthma history. Reported cough (23.4 % vs. 8.1 %) and
      shortness of breath (18.8 % vs. 6.5 %) were significantly higher in furniture
      decoration students than in controls (p = 0.016 and p = 0.034, respectively).
      Furniture-decoration students had higher conjunctivitis (34.4 % vs. 9.7 %, p =
      0.001) and rhinitis (34.4 % vs. 19.4 %, p = 0.044) history when compared with
      controls. Both students and controls were normal in terms of respiratory
      examination. PEF recordings were performed for approximately one month. Diurnal
      variability greater than 20 % was seen in 12/64 (18.7 %) of students at work,
      whereas it was detected in 4/62 (6.4 %) of controls (p = 0.034). When comparing
      for the presence of diurnal variability greater than 20 % in weekends, no
      difference was found between groups (p = 0.457). In conclusion, early detection
      of work-related respiratory changes by serial monitoring of peak expiratory flows
      should save the workers from hazardous respiratory effects of the furniture
      production, especially in young population.

PMID- 15236494
TI  - Airborne fungi in industrial environments--potential agents of respiratory
      diseases.
AB  - Investigations on airborne fungi in a poultry house, a swinery, a feed preparing
      and storing house, a grain mill, a wooden panel producing factory, and organic
      waste recycling facilities have been carried out in Lithuania. Low concentrations
      of fungal spores were detected in the wooden panel producing factory, the
      swinery, the feed preparing and storing house, and the poultry house; moderate
      concentrations were found in the organic waste recycling facilities; high
      concentrations were revealed at the grain mill. Species of Aspergillus oryzae, A.
      nidulans, P. expansum, Penicillium olivinoviride, P. claviforme and Botryotrichum
      longibrachiatum prevailed in the poultry farm; Geotrichum candidum, Cladosporium
      cladosporioides, C. herbarum, Penicillium viridicatum and P. fellutanum dominated
      in the swinery. Fungi of Penicillium viridicatum, P. expansum, Staphylotrichum
      coccosporum and Aspergillus oryzae prevailed in the feed preparing and storing
      house at the swinery. Cladosporium cladosporioides, C. herbarum, Penicillium
      viridicatum and Geotrichum candidum prevailed in the grain mill. Fungi ascribed
      as Paecilomyces puntonii, Rhizopus nodosus and R. stolonifer dominated in the
      wooden panel producing factory. Species of Aspergillus raperi, P. paxilli, P.
      oxalicum, and Cladosporium herbarum prevailed at the organic waste recycling
      facilities. According to published data, the majority of the identified fungal
      species are characterized as allergenic and an exposure to their spores may
      provoke adverse health effects (such as allergic rhinitis, bronchial asthma or
      extrinsic allergic alveolitis) in susceptible individuals.

PMID- 15236495
TI  - Occupational exposure to allergenic mites in a Polish zoo.
AB  - The study was carried out from April 2000-March 2001. During this period 49
      samples of dust, litter, debris and residues from cages and run-offs of mammals,
      birds and reptiles in the Silesian Zoo, were examined for the presence of mites,
      especially the allergenic taxa. Mites were extracted using the Berlese method and
      preserved in 70 % ethanol. For identification, the mites were mounted in Hoyer's
      medium on microscope slides. Mites were found in 44 of 49 samples analyzed (89.8
      %). A total of 5,097 mites were collected, from which 60.3 % were found in
      samples collected in spring, whereas only 13 % in summer and 24.1 % in autumn.
      The remaining 2.6 % of the total mite population was found in winter. Majority of
      mites (82.7 %) were collected from aviaries of macaws and cockatiels (Ara
      ararauna and Nymphicus hollandicus). A total of 10 species of astigmatid mites
      were identified that belong to 4 families--Acaridae, Glycyphagidae, Anoetidae and
      Pyroglyphidae. Generally, the allergenic mites of the order Astigmata constituted
      49.5 % of the total count. Among them Acarus farris was predominant (34 % of the
      total count), followed by Tyrophagus putrescentiae (4.7 %), Caloglyphus sp. (4.35
      %) and Acarus immobilis (4.31 %). Dermatophagoides farinae, the house-dust-mite
      species, was for the first time found in this environment. D. farinae (0.05 % of
      the total population) was associated with parrots, canids and artiodactyls.
      Summarizing, it should be stressed, that cages and run-offs of different mammals,
      aviaries of parrots and terrariums of snakes are important sources of some
      allergenic mites, especially A. farris and T. putrescentiae, that might cause
      allergies in workers.

PMID- 15236496
TI  - Environmental factors affecting the start of pollen season and concentrations of
      airborne Alnus pollen in two localities of Galicia (NW Spain).
AB  - Alnus pollen is an early component of the annual atmospheric aerosol of the north
      west regions of Spain, which causes the first occurrence of allergic symptoms.
      Seasonal and intra-daily variation of Alnus pollination, and the influence that
      main meteorological parameters exert, was studied in this paper. Monitoring was
      carried out from 1993-2002, by using two Lanzoni VPPS 2000 volumetric samplers.
      Once the atmospheric behaviour of this pollen had been identified, the final
      objective was to elaborate predictive models to determine the onset of the Alnus
      pollen season and its concentrations during the pollination period in two
      localities of north-west Spain (Santiago and Ourense). Winter chilling required
      to overcome the bud-dormancy period was similar in both cities, with around 800
      Chilling Hours (C.H.) and 5.5 degrees C threshold temperature. Calculation of
      heat requirement for bud growth was carried out with maximum temperature, with
      around 50 Growth Degree Days (G.D.D. degrees C) needed, with 6 degrees C
      threshold temperature. Data from 2002 were used in order to determine the real
      validity of the models. This year was not taken into account to establish the
      aforementioned models. The variation between the predicted start of the pollen
      season and the observed season was smallest in Ourense. Verifying the proposed
      models for predicting daily mean concentrations of Alnus pollen during the pollen
      season shows that the predicted curves fits the observed variations of daily mean
      concentrations.

PMID- 15236497
TI  - The occurrence and allergising potential of airborne pollen in West Bengal,
      India.
AB  - A continuous 2-year volumetric aerobiological survey was conducted in Berhampore
      town, a centrally located and representative part of West Bengal, India. The aim
      of the study was to assess the allergising potential of airborne pollen grains of
      West Bengal. A total of 31 pollen types were identified of which Poaceae
      (grasses) pollen showed maximum frequency, followed by Cyperaceae, Cassia sp.,
      Acacia auriculiformis, etc. The seasonal periodicities of the pollen types and
      their relationship to meteorological conditions were investigated. It was found
      that the pollen concentration is positively correlated with temperature and
      negatively correlated with rainfall and relative humidity. Clinical
      investigations by skin prick test were carried out to detect allergenicity of
      pollen types. Eighteen common airborne pollen types induced positive responses of
      which pollen extracts of Saccharum officinarum (grass), Azadirachta indica, Cocos
      nucifera, Phoenix sylvestris, Cyperus rotundus and Eucalyptus citriodora showed
      strongest sensitising potential. This result is consistent with previous
      investigations in different parts of West Bengal.

PMID- 15236498
TI  - Ragweed pollen in the air of Szczecin.
AB  - The aim of the study was to analyse the ragweed (Ambrosia) pollination in
      Szczecin (western Poland) in the years 2000-2002. Measurements were performed by
      the volumetric and gravimetric method. Pollen seasons were defined as the periods
      of 90 % of the total catch. Ragweed pollen is known as a very potent
      aeroallergen. In recent years ragweed appeared in Europe in hitherto unknown
      localities, and the number of people allergic to the allergens of this plant has
      been gradually increasing. In the period of the study a strong tendency towards
      increasing ragweed pollen counts in the air of Szczecin was noted. Of the three
      years studied, the lowest concentration of ragweed pollen observed in 2000
      equalled a few pollen grains in 1 m(3) per 24 h. In 2001, the highest airborne
      concentration of 30 grains in 1 m(3) per 24 h was noted at the end of August. The
      annual pollen count of ragweed in 2002 was 3 times higher than in 2001. The
      pollen season started in the second decade of August and lasted until the
      beginning of September. The highest airborne concentration of 98 grains in 1 m(3)
      per 24 h was noted at the beginning of September on a sunny day with strong wind.
      The pollen count of ragweed was found to depend on the weather conditions,
      especially on wind speed and relative humidity, diversity of local flora and long
      distance transportation.

PMID- 15236499
TI  - Livestock odours and quality of life of neighbouring residents.
AB  - Neighbours of intensive livestock production facilities frequently complain of
      odour annoyance. They are also concerned about potential negative health effects
      of environmental exposures to livestock emissions. Quality of life (QoL) was
      assessed in residents of a rural community neighbouring an area with high
      concentration of animal farms. A postal cross-sectional survey was carried out
      among the 4,537 residents, aged 18-44 years. Of these, 3,112 (69 %) responded to
      questions on annoyance by livestock odours (4-point scale), on QoL (assessed by
      the short form 12, SF-12), and on potential confounders (age, gender, respiratory
      symptoms, smoking, living on or close to a farm, and employment status). SF-12
      scores were available for 2745 (88 %) subjects. Sixty-one percent of the
      respondents complained about unpleasant odours, 91 % of these accused livestock
      as source of these odours. Physical and emotional SF-12 scores were inversely
      related to annoyance scores. Better risk communication might improve QoL in
      concerned neighbours of intensive livestock production facilities.

PMID- 15236500
TI  - Prevalence of asthma and some respiratory symptoms in the years 1995 and 2001 in
      schoolchildren from rural regions of Poland.
AB  - The aim of our study was to estimate the prevalence of asthma and some
      respiratory symptoms and diseases in schoolchildren from rural regions of Poland
      in 2001 and to compare these data with previous estimations in 1995. Repeated
      cross-sectional epidemiological studies were performed among 594 primary
      schoolchildren in 1995 and 541 in 2001 using the same standardized questionnaire.
      Lifetime prevalence of "doctor's-diagnosed asthma" increased significantly from
      3.4 % in 1995 to 9.6 % in 2001. This trend may be due to the real increase in the
      prevalence of asthma and also may be a result of better physician's diagnosis
      and/or better parents' health education. A substantial increase of asthma-related
      symptoms (post-exercise breathlessness, wheezing and dyspnoea) was also observed
      between these years (8.3-17.7 %, 6.2-13.2 % and 7.6-13.3 %, respectively). These
      results suggest that asthma in Polish schoolchildren is still underdiagnosed.

PMID- 15236501
TI  - Airway toxicity of house dust and its fungal composition.
AB  - House dust is an important source of different toxic metabolites as well as
      allergens, including those of fungal origin, in the indoor environment. A bio
      assay employing 1-day-old chick tracheas was used to characterize airway effects
      of 2-butanone and dimethylsulphoxide (Me2SO) extracts of 23 dust samples
      collected from water damaged (13) and control (10) Danish schools. Direct
      microscopical analysis of samples, followed by cultivation on dichloran 18 %
      glycerol agar at 25 degrees C for 10 days to establish their mycoflora, was
      performed. The in vitro ciliostatic potential of the chloroform-extractable endo-
      and exometabolites of 41 representative fungal isolates was determined. Nine dust
      extracts in 2-butanone (2 from damp rooms) or 10 (6) in Me(2)SO showed some
      ciliostatic activity in the 3-days' experiment. Fungal composition of dust from
      buildings with leakage was almost identical with that from undamaged houses, as
      well as the fungal colony counts from the damp schools and the control samples.
      Aspergillus spp. were prevalent in the samples - 31 or 40 % of all fungi,
      followed by Penicillium spp. and Cladosporium cladosporioides. Alternaria spp.,
      Chaetomium spp., Mucor spp., Mycelia sterilia, Paecilomyces variotii, Rhizopus
      sp., Ulocladium sp. and yeasts were each isolated in less than 8 % of the fungal
      content. No Aspergillus flavus isolate (8 in total) was aflatoxigenic,em>in
      vitro. Alternaria spp., Aspergillus spp., Botrytis cinerea, Penicillium spp., C.
      cladosporioides, Chaetomium spp. and Ulocladium sp.; in total, 88 % of all fungi
      tested, produced ciliostatically active metabolites. These toxigenic strains were
      also present in 4 dust samples from controls and 5 dust samples from water
      damaged buildings. Extracts of these dust samples were also toxic in bioassay.
      There were bio-detectable concentrations (10-20 microg of extracts/ml of the
      organ culture medium) of toxic compounds in house dust. Contribution of fungal
      metabolites to its toxic effect should be studied further.

PMID- 15236502
TI  - Trichothecene mycotoxins and their determinants in settled dust related to grain
      production.
AB  - We hypothesise that inhalant exposure to mycotoxins causes developmental outcomes
      and certain hormone-related cancers that are associated with grain farming in an
      epidemiological study. The aim of the present study was to identify and validate
      determinants of measured trichothecene mycotoxins in grain dust as work
      environmental trichothecene exposure indicators. Settled grain dust was collected
      in 92 Norwegian farms during seasons of 1999 and 2000. Production characteristics
      and climatic data were studied as determinants of trichothecenes in settled dust
      samples obtained during the production of barley (N = 59), oats (N = 32), and
      spring wheat (N = 13). Median concentrations of trichothecenes in grain dust were
      <20, 54, and < 50 mg/kg (ranges < 20-340, < 30-2400, and < 50-1200) for
      deoxynivalenol (DON), HT-2 toxin (HT-2) and T-2 toxin (T-2) respectively. Late
      blight potato rot (fungal) forecasts have been broadcast in Norway to help
      prevent this potato disease. Fungal forecasts representing wet, temperate, and
      humid meteorological conditions were identified as strong determinants of
      trichothecene mycotoxins in settled grain dust in this study. Differences in
      cereal species, production properties and districts contributed less to explain
      mycotoxin concentrations. Fungal forecasts are validated as indicators of
      mycotoxin exposure of grain farmers and their use in epidemiological studies may
      be warranted.

PMID- 15236503
TI  - Time of farmers' exposure to biological factors in agricultural working
      environment.
AB  - Working time in conditions of exposure to hazardous factors is an important
      element indispensable for the evaluation of human exposure in the working
      environment. Agricultural work is accompanied by co-occurrence of many risk
      factors threatening farmers' health, e.g. dust, elements of the thermal
      environment, noise, vibration, chemical and biological agents. Biological factors
      cause diseases with contagious, allergic or immuno-toxic backgrounds which
      constitute the majority of farmers' occupational diseases registered in Poland.
      Exposure to hazardous factors in agricultural working environment is due to
      contact with plants, animals and organic wastes, more precisely--with microbes,
      plant and animal particles present in aerogenic agricultural dust, as well as
      pathogens of contagious and invasive diseases present in contaminated soil, water
      and plants. Data concerning the duration of farmers' exposure to biological and
      other factors of the working environment were obtained with the use of the
      Private Farmer Work Chart. Time-schedule observations concerned an annual work
      cycle. The study covered 30 farms with the following production profiles: plant
      (Group A), animal (Group B) and mixed production (Group C). The total working
      time was: in Group A - from 106-163 % of the legal working time; in Group B -
      from 75-147 %; in Group C - from 136-167 %. Among 48 work activities contributing
      to the full working cycle among the farmers examined, 15 activities were
      accompanied by 5 factors. These were mainly field activities which covered plant
      harvesting and fertilizing, chemical plant protection, as well as cultivation
      activities. Agricultural dust and elements of the thermal environment were the
      environmental factors most frequently accompanying agricultural work, followed by
      contact with biological factors, noise, vibration, and chemical agents.
      Biological factors are a specific element associated with 19 work activities,
      mainly the spreading of manure, animal breeding and plant harvesting. Farmers'
      working time in conditions of exposure to these factors in the group of plant
      producers was 51 % of the total working time on average, among animal breeders-
      80 % and in the case of mixed production--77 %.

PMID- 15236504
TI  - Airborne pollen calendar of Lublin, Poland.
AB  - Pollen concentration in the atmosphere of Lublin (eastern Poland) was studied by
      means of volumetric method using Hirst sampler (VPPS 2000, Lanzoni) in 2001-2002.
      The pollen trap was mounted at the height of 15 m in the centre of Lublin. On the
      basis of analysis of mean daily values of pollen concentration, the pollen
      calendar was constructed for 16 taxa producing the allergenic pollen: Alnus,
      Corylus, Populus, Ulmus, Fraxinus, Betula, Carpinus, Quercus, Fagus, Pinaceae,
      Poaceae, Rumex, Plantago, Chenopodiaceae, Artemisia, Urticaceae. Great
      differences referring to the course of pollen seasons for most of the studied
      taxa of trees within the 2 years of study were found. They were associated with
      the beginning and end of the pollen season, the amount and the date of maximum
      pollen concentration occurrence, as well as annual sums of pollen grains. Much
      lower differentiation was observed in the case of herbaceous plants. This
      referred mainly to maximum concentration occurrence dates (Urtica, Poaceae) and
      the length of pollen season (Chenopodiaceae). The most similar course of pollen
      seasons during 2 years was recorded for Artemisia. Among trees, the highest
      pollen concentrations were recorded for Betula, Pinaceae and Alnus; the lowest
      for Ulmus, Fagus and Corylus. Very high concentration of herbaceous plant's
      pollen was observed for Poaceae and Urtica; Plantago and Chenopodiaceae showed
      the lowest level. Annual sums of pollen grains for Alnus, Populus, Quercus,
      Betula and Pinaceae were much higher in 2001, but in the case of Ulmus, Fraxinus,
      Carpinus, Fagus the annual sums of pollen grains in 2002 were almost twice as
      high as in 2001. For 5 among 7 herbaceous taxa, annual sums of pollen grains in
      both years were similar.

PMID- 15236506
TI  - The prevalence of spirochete Borrelia burgdorferi sensu lato in ticks Ixodes
      ricinus and mosquitoes Aedes spp. within a selected recreational area in the city
      of Szczecin.
AB  - The aim of this study was to determine the prevalence of spirochete Borrelia
      burgdorferi s.l. in ticks Ixodes ricinus and mosquitoes Aedes spp. within the
      Bukowa Forest, collected between 2000 and 2001. The study covered 215 ticks (193
      nymphs and 22 adults) and 947 mosquitoes female of the genus Aedes. Spirochetes
      of Borrelia burgdorferi s.l. were detected in the arthropods studied with the
      method of indirect immunofluorescence assay (IFA). Positive readings of the
      immunological reaction were stated in 17.7 % of the collected nymphs and adult
      forms of Ixodes ricinus, and in 0.8 % of mosquito females of the genus Aedes. The
      number of B. burgdorferi observed in a view field (400 x) of microscopic
      preparations of all infected mosquitoes and about 10 % of the infected ticks,
      ranged from 1-10. This number in 50 % of the nymphs was from 11-50 spirochetes.
      View fields of the preparations of the other 50 % of nymphs and adult forms
      featured more then 50 spirochetes. The observed low values of the prevalence and
      infection intensity of female mosquitoes Aedes spp. compared to ticks suggest
      that the former do not pose a serious epidemiological threat in the spreading of
      Lyme disease.

PMID- 15236505
TI  - Human anaplasmosis in north-eastern Poland: seroprevalence in humans and
      prevalence in Ixodes ricinus ticks.
AB  - Sera of 500 inhabitants of north-eastern Poland, 450 suspected for Lyme
      borreliosis and 50 blood donors (control group), were analysed for the presence
      of IgG antibodies against Anaplasma phagocytophilum, the causative agent of human
      anaplasmosis (HA), known so far as human granulocytic ehrlichiosis (HGE). Forty
      one (9.1 %) sera of the study group and one serum (2 %) of the control group were
      positive using indirect fluorescence assay (IFA). The seropositivity tended to be
      more frequent among males (10.3 %) than females (7.6 %) and among the rural (10.3
      %) than urban population (7.5 %); however, differences were of no statistical
      significance (p = 0.4). No age difference was found between the seropositive and
      the seronegative individuals (p = 0.77). The only factor increasing the risk of
      HA seropositivity found was forestry employment (p < 0.05). Additionally, a total
      of 559 Ixodes ricinus ticks, collected in the same area as sera, were
      investigated for the presence of A. phagocytophilum by the polymerase chain
      reaction (PCR) and 41 (8.7 %) of them were found to be positive. The infection
      level ranged from 2.3-13.7 %, depending on the area studied. Bacteria were
      significantly less frequently detected in nymphs - 2.1 % (5/235) than in adult
      ticks - 13.6 % (44/324) and in males--4.2 % (74/165) than in females--23.3 %
      (37/159) (p < or = 0.05). The obtained results confirm both the occurrence of HA
      foci in north-eastern Poland with I. ricinus as the principal vector of the A.
      phagocytophilum infection, and forestry workers as the main group at risk.

PMID- 15236507
TI  - Ixodes ricinus as a vector of Borrelia burgdorferi sensu lato, Anaplasma
      phagocytophilum and Babesia microti in urban and suburban forests.
AB  - In the suburban and urban forests in the cities of Gdansk, Sopot and Gdynia
      (northern Poland), Ixodes ricinus ticks should be considered as the vector of
      pathogenic microorganisms that may cause significant diseases in wild and
      domestic animals and humans. These microorganisms include etiologic agents of
      Lyme disease, human anaplasmosis (HA) and babesiosis: Borrelia burgdorferi sensu
      lato, Anaplasma phagocytophilum and Babesia microti, respectively. DNA extracts
      from 701 ticks collected in 15 localities were examined by PCR for the
      simultaneous detection of these 3 pathogens. Overall, 14 % were infected with A.
      phagocytophilum followed by 12.4 % with B. burgdorferi s.l. and 2.3 % with B.
      microti. In total, the percentage of infected females (32.9 %) was 2.4 times
      higher than in males (13.7 %) and 3.2 times higher than in nymphs (10.3 %). Among
      adult ticks (n = 303), 8.3 % were dually infected with A. phagocytophilum and B.
      burgdorferi s.l., 2.0 % with the agent of human anaplasmosis and B. microti and
      0.3 % with borreliae and B. microti.

PMID- 15236508
TI  - The efficacy of benzyl benzoate sprays in killing the storage mite Tyrophagus
      putrescentiae (Acari: Acaridae).
AB  - This study tested the effectiveness of benzyl benzoate (BB) in killing Tyrophagus
      putrescentiae (Schrank) mites when using the method utilized by regular
      consumers. The efficacy of the BB sprays was determined in laboratory experiments
      and semi-field experiments with mattress and mattress pad pieces. The mites were
      counted and their living status determined at different time points
      microscopically. In the laboratory experiment, the sprays containing either 0.5
      %/0.9 % BB with 70 % ethanol or 0.1 % BB with absolute ethanol were highly
      efficient, resulting in over 90 % mite mortality within 20-30 minutes. In the
      semi-field experiment, mimicking the home application, the sprays were applied to
      pieces of a mattress and a mattress pad, and allowed to affect the area for 30
      minutes before thorough vacuuming. The recovery of mites was usually less than 10
      %. The sprays containing BB were effective in killing the mites in the
      laboratory, but success was less prominent in the semi-field tests. This method
      could be used in testing other compounds for their efficacy in killing mites.

PMID- 15236509
TI  - Immunologic reactivity to work-related airborne allergens in people
      occupationally exposed to dust from herbs.
AB  - A group of 150 people occupationally exposed to dust from herbs were examined.
      The examined group consisted of 47 thyme farmers, 32 chamomile farmers, 31 sage
      farmers and 40 workers of herbs processing industry. As a reference group, 50
      urban dwellers, not exposed to any kind of organic dust, were examined. Skin
      prick tests and precipitin tests were conducted with, respectively, 4 and 11
      microbial antigens associated with organic dust. Both skin and precipitin tests
      were also conducted with herbal extracts of chamomile and sage. Precipitin tests
      were carried out with sera not concentrated and sera 3-fold concentrated. Tests
      for inhibition of leukocyte migration (MIF) were also conducted with 4 microbial
      antigens. People occupationally exposed to dust from herbs showed a higher
      frequency of positive skin reactions to microbial antigens compared to the
      reference group. The results of precipitin test also revealed greater reactivity
      to the environmental microbial antigens in the examined group, compared to the
      reference group. The highest frequency of positive results was noted with the
      antigen of Pantoea agglomerans (30.6 % with sera not concentrated and 48.3 % with
      sera 3-fold concentrated) - the difference compared to the reference group (12.0
      %) was highly significant (p < 0.01). The frequencies of positive results of MIF
      test in the examined group were high with all antigens tested: Arthrobacter
      globiformis (12.6 %), Pantoea agglomerans (11.1 %), Saccharopolyspora
      rectivirgula (17.0 %), Aspergillus fumigatus (13.3 %), and, compared to the
      reference group with no positive result for any antigen, all the differences were
      significant (p < 0.05). In conclusion, the frequency of positive allergological
      reactions to airborne microorganisms was high in people occupationally exposed to
      dust from herbs and suggests a potential role of microbial allergens in the
      pathogenesis of work-related health disorders among herb workers. The risk of
      sensitization seems to be greatest among thyme farmers, who showed the highest
      positive response. The results confirmed the particular allergenic importance of
      Gram-negative bacterium Pantoea agglomerans.

PMID- 15236510
TI  - Exposure of hop growers to bioaerosols.
AB  - Air sampling was performed during picking and sorting of hop (Humulus lupulus)
      cones on 19 hop farms located in eastern Poland. The concentration and
      composition of airborne microflora and the concentration of airborne dust and
      endotoxin were determined. Additionally, 7 samples of settled hop dust were
      collected and examined for the presence of microorganisms and endotoxin. Total
      concentrations of airborne microorganisms were within a range of 2.08-129.58 x
      10(3) cfu/m(3). Gram-positive bacteria formed 22.2-96 % of the total count. Among
      them, prevailed corynebacteria and endospore-forming bacilli. Fungi constituted
      3.7-65.4 % of the total count. The dominant species were Penicillium citrinum,
      Alternaria alternata, and Cladosporium epiphyllum. Thermophilic actinomycetes and
      Gram-negative bacteria were detected in the air of only 10 and 6 farms,
      respectively. Airborne dust concentrations at the workplace ranged from 0.17
      31.67 mg/m(3). The concentrations of airborne endotoxin were in the range of 26
      6250 ng/m(3). In the samples of settled dust, the concentrations of total
      microorganisms ranged from 0.25 x 10(6) to 2.87 x 10(8) cfu/g. Gram-positive and
      Gram-negative bacteria constituted respectively 3.2-98 % and 0-93.5 % of the
      total count. Fungi formed 0-30.3 % of the total count. The most common species
      were Penicillium spp. and Alternaria alternata. The concentrations of endotoxin
      were in the range of 312.5-6250 microg/g (median 6250 microg/g). The presence of
      microorganisms and endotoxin in the samples of settled dust was confirmed by
      electron microscopy. The hop growers seem to be exposed to lower concentrations
      of dust, microorganisms and endotoxin compared to other branches of agriculture.
      This may be partly due to antimicrobial properties of hop plant. Among microbial
      factors associated with hop dust, bacterial endotoxin and allergenic fungi pose
      the greatest potential hazard for exposed hop farmers.

PMID- 15236511
TI  - Small mammals (Insectivora, Rodentia) as a potential source of chlamydial
      infection in East Slovakia.
AB  - The presence of antibodies against Chlamydophila (Chlamydia) psittaci in small
      mammals (Insectivora, Rodentia) in the region of East Slovakia are presented. The
      hosts were caught in several areas of Slovakia in habitats with different levels
      of anthropogenic disturbance. Research was carried out during 2000-2002. The
      authors examined 1,947 sera coming from 4 insectivore and 10 rodent species. Each
      serum was examined by micromethod of complement binding reactions using antigen
      Chlamydophila (Chlamydia) psittaci. Chlamydial infections were found in 251
      individuals (prevalence 12.9 %) of 8 mammal species. The antichlamydial
      antibodies were proved at levels ranging from 1:32-1:1024. The highest prevalence
      of antibodies was detected in the most abundant rodent species Apodemus microps
      (14.8 %), Apodemus agrarius (13.9 %), Apodemus flavicolis (12.4 %), Microtus
      arvalis (12 %), and Clethrionomys glareolus (10.9 %). Positive hosts were
      registered in all studied localities. Testing of prevalence values in the
      individual research years confirmed significant changes. Our results showed that
      small mammals probably play an important role in the circulation of chlamydiae in
      nature.

PMID- 15236512
TI  - Antinuclear antibodies are not increased in the early phase of Borrelia
      infection.
AB  - In the literature, there are case reports suggesting that Borrelia burgdorferi
      infection may induce autoimmune diseases dependent on antinuclear antibodies
      (ANA). The present study was undertaken in order to verify this possibility in a
      prospective manner. The study group comprised 78 consecutive patients (51 women
      and 27 men, median age 41.5 years) referred to our Department for the serologic
      diagnosis of Borrelia infection. The patients' sera were tested for Borrelia
      specific IgM and IgG (Recombinant Antigen Enzyme Immunoassays, Biomedica).
      Antibodies against Borrelia were detected in 31 (39.7 %) persons. 15 persons
      (19.2 %) had positive IgM, another 15 (19.2 %)--positive IgG, and 1 person (3.2
      %)--both IgM and IgG. Frequent positivity of IgM antibodies suggests that persons
      in the early phase of infection prevailed in the group. Tests for anti-dsDNA,
      anti-RNP, anti-Sm antibodies, and a screening test for systemic rheumatic
      diseases (ANA Rheuma Screen) were carried out using Varelisa Enzyme Immunoassays
      (Pharmacia and Upjohn). The spectrum of autoimmune diseases covered by these
      tests included SLE, MCTD, Sjogren's syndrome, scleroderma, polymyositis, and
      dermatomyositis. ANA were detected in 15 persons (19.2 %): anti-dsDNA in 7 (9.0
      %), anti-RNP in 1 (1.3 %), anti-Sm in 2 (2.6 %), and ANA Rheuma Screen was
      positive in 6 persons (7.7 %). Statistical analysis of differences in the ANA
      frequency between Borrelia-positive and -negative groups was carried out using
      Fisher's exact chi-square test (both without and with gender and age matching).
      No significant differences were found between the groups. Based on the above
      results, we conclude that there is no increase in the frequency of antinuclear
      antibodies in the early phase of Borrelia infection.

PMID- 15236513
TI  - Pesticide exposure in dwellings near bulb growing fields in The Netherlands: an
      explorative study.
AB  - An explorative field study was conducted to assess residential exposure to
      pesticides, regularly applied in bulb farming. House dust floor samples were
      taken from homes of bulb farmers (n = 12) and from homes in close proximity to a
      bulb field (i.e. non-farmers) (n = 15). Samples were analysed for 7 pesticides
      used by bulb growers in the sampling period. Of these pesticides, chloropropham,
      flutolanil and vinchlozolin could be detected in non-farmers homes. All
      pesticides were detected in farmers' homes, except metamitron. Median
      concentrations for chloropropham were significantly higher in farmers' homes
      (0.05 vs. 0.20 microg/m(2), p = 0.03). Logistic regression analyses showed that
      the odds for detecting pesticides were higher in farmers' compared to non
      farmers' homes and remained higher after correction for potential confounders.
      Results showed no significant effect of proximity of a residence to a bulb field
      for median concentrations of pesticides; however, logistic regression analysis
      showed a borderline statistically significant effect for detecting chloropropham
      above the detection limit (OR = 10, p = 0.08). These findings demonstrate that,
      as expected, risk of exposure is higher for bulb farmers than for non-farmers.
      They also indicate that exposure to pesticides is not limited to bulb farmers
      only, and this warrants further investigation.

PMID- 15236515
TI  - Spin canting in the 3D anionic dicyanamide structure (SPh(3))Mn(dca)(3) (Ph =
      phenyl, dca = dicyanamide).
AB  - Through use of the SPh(3)(+) (Ph = phenyl, C(6)H(5)) cation as a molecular
      template, a new three-dimensional Mn(dca)(3)(-) [dca = dicyanamide, N(CN)(2)(-)]
      anionic structure has been crystallized. At room temperature, (SPh(3))Mn(dca)(3)
      (1) crystallizes in the monoclinic space group P2(1)/c, with a = 11.7079(5) A, b
      = 12.8554(5) A, c = 16.8605(6) A, beta = 100.666(2) degrees, and V = 2493.8(3)
      A(3). Magnetic susceptibility measurements indicate that this salt exhibits a
      spin canted long range antiferromagnetically ordered ground state below 2.5 K.

PMID- 15236514
TI  - Incidence and prevalence of infection with Anaplasma phagocytophilum. Prospective
      study in healthy individuals exposed to ticks.
AB  - The seroprevalence of human granulocytic anaplasmosis (former human granulocytic
      ehrlichiosis, HGE) has been documented in several studies, but little data exists
      on incidence rates in healthy individuals. In a prospective study, we tested 125
      healthy adults (mean age 43 years)--workers of the Bialowieza Primeval Forest
      National Park, north-eastern Poland--for Anaplasma phagocytophilum IgG antibodies
      using an indirect immunofluorescence antibody assay, and for Borrelia burgdorferi
      IgG with ELISA in a 12-month interval. The data concerning clinical symptoms
      consistent with human granulocytic anaplasmosis were collected using a
      standardized questionnaire. Of these 125 subjects, 9 were anti-A. phagocytophilum
      positive at the study entry. Four participants (3.2 %) seroconverted from IgG
      negative to positive during the observation period. Three subjects (2.4 %)
      converted from initially anti-A. phagocytophilum positive to negative. Specific
      IgG antibodies against Borrelia burgdorferi were detected in 27 (21.6 %)
      individuals. Concurrence of Borrelia burgdorferi and Anaplasma phagocytophilum
      was observed in 3.2 %, whereas 4 % were Anaplasma phagocytophilum IgG positive
      and Borrelia burgdorferi IgG negative (not significant). Clinical symptoms
      associated with human granulocytic anaplasmosis were not present in
      seroconverting individuals. The obtained results confirm the occurrence of
      Anaplasma phagocytophilum infection in north-eastern Poland with asymptomatic
      clinical course.

PMID- 15236516
TI  - Spin crossover in a tetranuclear Cr(III)-Fe(III)(3) complex.
AB  - A novel heteronuclear exchange-coupled complex
      [Cr(III)[(CN)Fe(III)((5)L)](3)(CN)(3)] containing a pentadentate blocking ligand
      (5)L was synthesized. The X-ray structure shows that a meridional isomer applies
      with inequivalent Fe(III) centers. The complex exhibits a thermally induced spin
      crossover along with the exchange coupling. Mossbauer spectra indicate a spin
      transition between S = (1)/(2) and S = (5)/(2) states although a considerable
      amount of Fe(III) centers stays high-spin at T = 6 K. The magnetization, the
      magnetic susceptibility, and the Mossbauer data were fitted in one run with a
      spin crossover model taking into account exchange interactions among all metal
      centers.

PMID- 15236517
TI  - [C(6)H(5)NH(CH(3))(2)](2)Te(2)I(10): secondary I...I bonds build up a 3D network.
AB  - The crystal structure of [C(6)H(5)NH(CH(3))(2)](2)Te(2)I(10) consists of the N,N
      dimethylanilinium cation and a hitherto unreported tellurium iodide anion
      Te(2)I(10)(2)(-) [crystal data: C(8)H(12)NTeI(5), monoclinic, P2(1)/c, a =
      9.4787(2) A, b = 14.2874(3) A, c = 13.6869(3) A, beta = 95.1918(8) degrees, V =
      1845.96(7) A(3), Z = 4]. The Te(2)I(10)(2)(-) dianion is based on two edge
      sharing TeI(6)(2)(-) octahedra, and interestingly, it builds up a three
      dimensional Te(IV)-I open framework through extensive interconnecting I.I
      contacts. These I.I contacts (3.66-3.80 A) are significantly shorter than the
      corresponding sum of van der Waals radii (4.0 A) and may potentially promote
      charge carrier migration throughout the Te-I network. This material can also be
      drop-cast into thin films from a heated DMF solution.

PMID- 15236518
TI  - Ozonic acid and its ionic salts: ab initio probing of the O(4)(2)(-) dianion.
AB  - The pyramidal O(4)(2)(-) dianion is valence isoelectronic to the well-known
      ClO(3)(-) and SO(3)(2)(-) anions, and yet it has not been observed. The synthesis
      of any molecule containing such a dianion would represent a major breakthrough in
      making molecules containing more than three covalently bound oxygen atoms. We
      found that the parent H(2)O(4) ozonic acid is unstable in the form of the valence
      isoelectronic sulfurous acid H(2)SO(3). Our quantum chemical probing of the
      Li(2)O(4) ionic salt molecule is inconclusive. However, we found that the
      specially designed FLi(3)O(4) gas phase molecule is a true metastable species and
      could be considered as the first molecule containing the O(4)(2)(-) dianion. Our
      theoretical prediction of the first compound containing the tetraatomic
      covalently bound O(4)(2)(-) dianion opens the possibility to even more oxygen
      rich compounds, which will have a great potential as high density oxygen storage.

PMID- 15236519
TI  - Formation of high concentrations of BrO(2) in acidic bromate solutions.
AB  - A new procedure to produce the BrO(2) transient species allowed time-resolved UV
      vis spectra that show a structured band (lambda(max) = 502 nm) in dichloromethane
      to be obtained. In water, because of the increase of the dielectric constant, the
      lambda(max) presents a blue shift to 474 nm and the species decomposes much
      faster. The time-resolved spectra show evidence for its equilibrium with a
      nonidentified colorless form. This route opens new possibilities to the study
      this species in solution.

PMID- 15236520
TI  - Solvent effects on the conversion of dicopper(II) micro-eta(2):eta(2)-peroxo to
      bis-micro-oxo dicopper(III) complexes: direct probing of the solvent interaction.
AB  - A new tridentate ligand, PYAN, is employed to investigate solvent influences for
      dioxygen reactivity with [Cu(PYAN)(MeCN)]B(C(6)F(5))(4) (1). Stopped-flow kinetic
      studies confirm that the adducts [[u(II)(PYAN)]2)(O(2))][B(C(6)F(5))(4)](2)
      (2(Peroxo)) and [[u(III)(PYAN)]2)(O)(2)][B(C(6)F(5))(4)](2) (2(Oxo)) are in rapid
      equilibrium. Thermodynamic parameters for the equilibrium between 2(Peroxo) and
      2(Oxo) re as follows: THF, deltaH degrees approximately -15.7 kJ/mol, deltaS
      degrees approximately -83 J/K.mol; acetone, deltaH degrees approximately -15.8
      kJ/mol, deltaS degrees approximately -76 J/K.mol. UV-visible absorption and
      resonance Raman spectroscopic signatures demonstrate that the equilibrium is
      highly solvent dependent; the mixture is mostly 2(Peroxo) in CH(2)Cl(2), but
      there are significantly increasing quantities of 2(Oxo) along the series
      methylene chloride --> diethyl ether --> acetone --> tetrahydrofuran (THF).
      Copper(II)-N(eq) stretches (239, 243, 244, and 246 cm(-)(1) in CH(2)Cl(2),
      Et(2)O, acetone, and THF, respectively) are identified for 2(Peroxo), but they
      are not seen in 2(Oxo), revealing for the first time direct evidence for solvent
      coordination in the more open 2(Peroxo) structure.

PMID- 15236522
TI  - Functionalized thiosemicarbazone clusters of copper(I) and silver(I).
AB  - Reaction of [Cu(MeCN)(4)](+) with thiosemicarbazones bearing groups such as
      phenol, pyridine, or ferrocene gives tetranuclear or hexanuclear clusters with
      functional substituents; analogous air stable fluorescent clusters can also be
      prepared with Ag(I).

PMID- 15236521
TI  - Iron and copper complexes of tetraphenyl-m-benziporphyrin: reactivity of the
      internal C-H bond.
AB  - Iron and copper complexes of tetraphenyl-m-benziporphyrin (TPmBPH)H have been
      prepared and structurally characterized. The iron system, (TPmBPH)Fe(II)Br,
      contains a high-spin Fe(II) center. In the solid state the complex forms dimeric
      units linked by weak CH.Br hydrogen bonds. The Cu complex contains a tetrameric
      copper cluster with a Cu(2)Cl(4)(2)(-) unit bridging two [(TPmBPCl)Cu(II)](+)
      fragments. The formation of (TPmBPCl)H represents an example of copper-catalyzed
      chlorination on the internal carbon atom of (TPmBPH)H.

PMID- 15236523
TI  - 1-D cobalt(II) spin transition compound with strong interchain interaction:
      [Co(pyterpy)Cl(2)].X.
AB  - Cobalt(II) compounds [Co(pyterpy)Cl(2)].MeOH (1.(MeOH)) and
      [Co(pyterpy)Cl(2)].2H(2)O (1.(2H(2)O)) were synthesized. The compound 1.(MeOH)
      forms the quasi 3-D networks by making pi-pi stacking between the 1-D chains. The
      methanol molecules from 1.(MeOH) can be removed by heating, and substituted by
      absorption of water molecules. The MeOH molecules in 1.(MeOH) are removed by
      heating at 410 K, and they are substituted by water molecules to form 1.(2H(2)O).
      1.(2H(2)O) exhibits a S = (3)/(2) (HS) left arrow over right arrow S = (1)/(2)
      (LS) spin transition with a thermal hysteresis. We have succeeded in constructing
      a guest dependent 1-D spin-crossover cobalt(II) compound.

PMID- 15236524
TI  - Quantum mechanical models of the resting state of the vanadium-dependent
      haloperoxidase.
AB  - Density functional theory has been used to investigate structural and electronic
      properties of complexes related to the resting form of the active site of
      vanadium haloperoxidase as a function of environment and protonation state.
      Results obtained by studying models of varying size and complexity highlight the
      influence of environment and protonation state on the structure and stability of
      the metal cofactor. The study shows that, in the trigonal bipyramidal active
      site, where one axial position is occupied by a key histidine, the trans position
      cannot contain a terminal oxo group. Further, a highly negatively charged
      vanadate unit is not stable. Protonation of at least one equatorial oxo ligand
      appears necessary to stabilize the metal cofactor. The study also indicates that,
      while at rest within the protein, the vanadate unit is most likely an anion with
      an axial hydroxide and an equatorial plane containing two oxos and a hydroxide.
      For the neutral, protonated state of the vanadate unit, there were two minima
      found. The first structure is characterized by an axial water with two oxo and
      one hydroxo group in the equatorial plane. The second structure contains an axial
      hydroxo group and an equatorial plane composed of one oxo and two hydroxo oxygen
      atoms. These two species are not significantly different in energy, indicating
      that either form may be important during the catalytic cycle. These data support
      the initial crystallographic assignment of an axially bound hydroxide, but an
      axial water is also a possibility. This study also shows that the protonation
      state of the vanadate ion is most likely greater than previously proposed.

PMID- 15236525
TI  - Synthesis, structure, and magnetic properties of a Mn(21) single-molecule magnet.
AB  - The reaction of [Mn(3)O(O(2)CMe)(6)(py)(3)](ClO(4)) (1; 3Mn(III)) with
      [Mn(10)O(4)(OH)(2)(O(2)CMe)(8)(hmp)(8)](ClO(4))(4) (2; 10Mn(III)) in MeCN affords
      the new mixed-valent complex
      [Mn(21)O(14)(OH)(2)(O(2)CMe)(16)(hmp)(8)(pic)(2)(py)(H(2)O)](ClO(4))(4) (3;
      3Mn(II)-18Mn(III); hmp(-) is the anion of 2-(hydroxymethyl)pyridine), with an
      average Mn oxidation state of +2.85. Complex 3.7MeCN crystallizes in the
      triclinic space group P. The structure consists of a low symmetry
      [Mn(21)(micro(4)-O)(4)(micro(3)-O)(12)(micro-O)(16)] core, with peripheral
      ligation provided by 16 MeCO(2)(-), 8 hmp(-), and 2 pic(-) groups and one
      molecule each of water and pyridine. The magnetic properties of 3 were
      investigated by both dc and ac magnetic susceptibility measurements. Fitting of
      dc magnetization data collected in the 0.1-0.8 T and 1.8-4.0 K ranges gave S =
      (17)/(2), D approximately -0.086 cm(-)(1), and g approximately 1.8, where S is
      the molecular spin of the Mn(21) complex and D is the axial zero-field splitting
      parameter. ac susceptibility studies in the 10-997 Hz frequency range reveal the
      presence of a frequency-dependent out-of-phase ac magnetic susceptibility
      (chi(M)' ') signal consistent with slow magnetization relaxation rates. Fitting
      of dc magnetization decay versus time data to the Arrhenius equation gave a value
      of the effective barrier to relaxation (U(eff)) of 13.2 K. Magnetization versus
      applied dc field sweeps exhibited hysteresis. Thus, complex 3 is a new member of
      the small but growing family of single-molecule magnets.

PMID- 15236526
TI  - Modeling novel radiopharmaceuticals: mono-C6-substituted PnAO ligands (PnAO =
      3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime).
AB  - The solid-state behavior of six novel 6-substituted PnAO (propylene amine oxime)
      complexes (6-11) involving Tc(V), Co(III), and Cu(II) salts is reported. Each of
      the Tc complexes 6-8 has the C6-substituent located equatorially in a six
      membered chelate ring involving a Tc=O unit which has the expected boat geometry.
      The C6-substituent therefore has little effect on the conformational behavior of
      the PnAO complex and thus provides an attractive site for further modification.
      The Co(III) complex 9 has the expected octahedral geometry, while the Cu(II)
      complexes 10 and 11 form square-based pyramids capped by water molecules. One
      Cu(II) system (10) contains two unique complexes in the asymmetric unit which are
      associated via multiple hydrogen bonds to a BF(4) anion, the remaining BF(4)
      anion being loosely hydrogen bonded to a coordinating water molecule. The cobalt
      and copper complexes 9-11 each exhibit a chair conformation for the six-membered
      chelate ring.

PMID- 15236527
TI  - Supramolecular spin-crossover iron complexes based on imidazole-imidazolate
      hydrogen bonds.
AB  - The [Fe(II)(H(3)L)](BF(4))(2).3H(2)O (1) complex was synthesized, where H(3)L
      (tris[[2-[(imidazole-4-yl)methylidene]amino]ethyl]amine) is a tripodal ligand
      obtained by condensation of tris(2-aminoethyl)amine and 4-formylimidazole (fim)
      in a 1:3 molar ratio. Starting from 1, a series of complexes,
      [Fe(II)(H(1.5)L)](BF(4))(0.5) (2) (=[Fe(II)(H(3)L)][Fe(II)(L)]BF(4)),
      [Fe(H(1.5)L)]BF(4) (3) (=[Fe(II)(H(3)L)][Fe(III)(L)](BF(4))(2)),
      [Fe(III)(H(3)L)](BF(4))(3).fim.H(2)O (4), and [Fe(III)(L)].2.5H(2)O (5), has been
      synthesized and characterized. The single-crystal X-ray structure of each complex
      has been determined. The Fe(II) compound, 2, and a mixed valence Fe(II)-Fe(III)
      compound, 3, involve formally hemi-deprotonated ligands, H(1.5)L. The structure
      of 3 consists of a homochiral two-dimensional assembled sheet, arising from the
      intermolecular hydrogen bonds between [Fe(II)(H(3)L)](2+) and [Fe(III)(L)](0)
      (3). All but 5 exhibit spin crossover between low-spin (LS) and high-spin (HS)
      states. This is a rare case where both Fe(II) and Fe(III) complexes containing
      the same ligand exhibit spin-crossover behavior. Magnetic susceptibility and
      Mossbauer studies showed that 3 has three accessible electronic states: LS Fe(II)
      LS Fe(III), HS Fe(II)-LS Fe(III), and HS Fe(II)-HS Fe(III). Compounds 1-3 show
      the light-induced excited spin-state trapping effect at the Fe(II) sites upon
      irradiation with green light. The solution magnetic properties, electronic
      spectra, and electrochemical properties of 1, 4, and 5 were also studied.

PMID- 15236528
TI  - Stable, chloride-induced monohapto-bonding mode for an allyl ligand in a Pd(II)
      complex bearing a new bidentate phosphonite-oxazoline ligand.
AB  - Bidentate ligands can lead to stable eta(1)-allyl complexes of Pd(II). A novel
      chelating phosphonite-oxazoline P,N ligand, abbreviated NOPO(Me2), has been
      prepared by reaction of 6-chloro-6H-dibenz[c,e][1,2]oxaphosphorin with the
      lithium alcoholate derived from 4,4-dimethyl-2-(1-hydroxy-1-methylethyl)-4,5
      dihydrooxazole. Its reaction with [Pd(eta(3)-C(3)H(5))(micro-Cl)](2) afforded the
      new eta(1)-allyl Pd complex [PdCl(eta(1)-C(3)H(5))(NOPO(Me2))] 2 in 91% yield.
      This constitutes a still rare example of structurally characterized eta(1)-allyl
      Pd(II) complex. Chloride abstraction led to the corresponding cationic eta(3)
      allyl complex [Pd(eta(3)-C(3)H(5))(NOPO(Me2))]PF(6) 3, which has also been
      characterized by X-ray diffraction. CO insertion into the Pd-C sigma-bond of the
      eta(1)-allyl ligand of 2 afforded the corresponding 3-butenoyl palladium complex
      [PdCl[C(O)C(3)H(5)](NOPO(Me2))] 4 under mild conditions, which supports the view
      that CO insertion into eta(3)-allyl palladium cationic complexes occurs via first
      coordination of the counterion to form a more reactive eta(1)-allyl intermediate.

PMID- 15236529
TI  - Imidazole and imidazolate iron complexes: on the way for tuning 3D-structural
      characteristics and reactivity. Redox interconversions controlled by protonation
      state.
AB  - X-ray structures for six Fe(II) and Fe(III) complexes from two closely
      heptadentate N-tripodal ligands, L1H(3) = tris[(imidazol-4-yl)-3-aza-3
      butenyl]amine and L2H(3) = tris[(imidazol-2-yl)-3-aza-3-butenyl]amine, are
      described: three complexes in the L1 series (namely, [Fe(II)(L1H(3))](2+) and
      [Fe(III)(L1H(3))](3+) at low pH and [Fe(III)(L1)](0) at high pH) and three
      complexes in the L2 series (namely, [Fe(II)(L2H(3))](2+) at low pH and
      [Fe(II)(L2H)](0) and [Fe(III)(L2)](0) at high pH). Most of these complexes are
      stable in both Fe(II) and Fe(III) redox states and with the ligand in various
      protonation states. In the solid state, hydrogen bonds networks were obtained.
      Structural differences induced by 2- or 4-imidazole substitution are described
      and discussed. In solution, interconversions between different forms, with regard
      to oxidation and protonation states, were investigated by UV-visible
      spectroscopy, cyclic voltammetry, and potentiometry. The deprotonation pattern of
      these polyimidazole iron(II) and iron(III) complexes is described in detail.
      pK(a)s of the imidazolate/imidazole moieties in MeOH/H(2)O are reported. Two new
      species, namely, [Fe(II)(L1)](-) and [Fe(II)(L2)](-), were shown to be obtained
      in DMSO upon strong base addition and characterized by UV-vis spectroscopy and
      cyclic voltammetry. Half-wave potentials of Fe(III)/Fe(II) complexes with ligand
      moieties in several protonation states are reported, both in DMSO and in
      MeOH/H(2)O. Because of the presence of free imidazole groups coordinated to the
      iron, the potential of the iron(III)/iron(II) couples can be tuned by pH. A shift
      of DeltaE = E(deprot) - E(prot) ranging from -270 to -320 mV per exchanged proton
      in DMSO was measured. This study shows moreover that interconversions (with
      regard to both redox and protonation states) can be reversed several times. As
      the complexes have been isolated in order to be tested as superoxide dismutase
      mimics, preliminary reactions with dioxygen and with superoxide, considered as
      oxidant and reducer of biological importance, are reported. In these two series,
      O(2)(-) behaves either as a base or as a reducer and no adducts have been
      observed.

PMID- 15236530
TI  - Correlation of structure and function in oligonuclear zinc(II) model
      phosphatases.
AB  - A series of pyrazolate-based dizinc(II) complexes has been synthesized and
      investigated as functional models for phosphoesterases, focusing on correlations
      between hydrolytic activity and molecular parameters of the bimetallic core. The
      Zn...Zn distance, the (bridging or nonbridging) position of the Zn-bound
      hydroxide nucleophile, and individual metal ion coordination numbers are
      controlled by the topology of the compartmental ligand scaffold. Species
      distributions of the various dizinc complexes in solution have been determined
      potentiometrically, and structures in the solid state have been elucidated by X
      ray crystallography. The hydrolysis of bis(p-nitrophenyl)phosphate (BNPP)
      promoted by the dinuclear phosphoesterase model complexes has been investigated
      in DMSO/buffered water (1:1) at 50 degrees C as a function of complex
      concentration, substrate concentration, and pH. Coordination of the
      phosphodiester has been followed by ESI mass spectrometry, and bidentate binding
      could be verified crystallographically in two cases. Drastic differences in
      hydrolytic activity are observed and can be attributed to molecular properties. A
      significant decrease of the pK(a) of zinc-bound water is observed if the
      resulting hydroxide is involved in a strongly hydrogen-bonded intramolecular
      O(2)H(3) bridge, which can be even more pronounced than for a bridging hydroxide.
      Irrespective of the pK(a) of the Zn-bound water, a hydroxide in a bridging
      position evidently is a relatively poor nucleophile, while a nonbridging
      hydroxide position is more favorable for hydrolytic activity. Additionally, the
      metal array has to provide a sufficient number of coordination sites for
      activating both the substrate and the nucleophile, where phosphate diesters such
      as BNPP preferentially bind in a bidentate fashion, requiring a third site for
      water binding. Product inhibition of the active site by the liberated (p
      nitrophenyl)phosphate is observed, and the product-inhibited complex could be
      characterized crystallographically. In that complex, the phosphate monoester is
      found to cap a rectangular array of four zinc ions composed of two bimetallic
      entities.

PMID- 15236531
TI  - Synthesis, structure, and magnetic properties of a [Mn22] wheel-like single
      molecule magnet.
AB  - The synthesis and magnetic properties of the compound
      [Mn(22)O(6)(OMe)(14)(O(2)CMe)(16)(tmp)(8)(HIm)(2)] 1 are reported. Complex 1 was
      prepared by treatment of [Mn(3)O(MeCO(2))(6)(HIm)(3)](MeCO(2)) (HIm = imidazole)
      with 1,1,1-tris(hydroxymethyl)propane (H(3)tmp) in MeOH. Complex 1.2MeOH
      crystallizes in the orthorhombic space group Pbca. The molecule consists of a
      metallic core of 2 Mn(IV), 18 Mn(III), and 2 Mn(II) ions linked by a combination
      of 6 micro(3)-bridging O(2)(-) ions, 14 micro(3)- and micro(2)-bridging MeO(-)
      ions, 16 micro-MeCO(2)(-) ligands, and 8 tmp(3)(-) ligands, which use their
      alkoxide arms to bridge in a variety of ways. The metal-oxygen core is best
      described as a wheel made from [Mn(3)O(4)] partial cubes and [Mn(3)O] triangles.
      Variable-temperature direct current (dc) magnetic susceptibility data were
      collected for complex 1 in the 1.8-300 K temperature range in a 1 T applied
      field. The chi(M)T value steadily decreases from 56 cm(3) K mol(-)(1) at 300 K to
      48.3 cm(3) K mol(-)(1) at 30 K and then increases slightly to reach a maximum
      value of 48.6 cm(3) K mol(-)(1) at 15 K before dropping rapidly to 40.3 cm(3) K
      mol(-)(1) at 5 K. The ground-state spin of complex 1 was established by
      magnetization measurements in the 0.1-2.0 T and 1.80-4.00 K ranges. Fitting of
      the data by a matrix-diagonalization method to a model that assumes only the
      ground state is populated and incorporating only axial zero-field splitting
      (DS(z)()(2)), gave a best fit of S = 10, g = 1.96 and D = -0.10 cm(-)(1). The ac
      magnetization measurements performed on complex 1 in the 1.8-8 K range in a 3.5 G
      ac field oscillating at 50-1000 Hz showed frequency-dependent ac susceptibility
      signals below 3 K. Single-crystal hysteresis loop and relaxation measurements
      indicate loops whose coercivities are strongly temperature and time dependent,
      increasing with decreasing temperature and increasing field sweep rate, as
      expected for the superparamagnetic-like behavior of a single-molecule magnet,
      with a blocking temperature (T(B)) of approximately 1.3 K.

PMID- 15236532
TI  - Exchange interactions and theoretical analysis of (31)P NMR spectra in
      VO(HPO(4)).0.5H(2)O.
AB  - Based on combined DFT/broken symmetry approach, a theoretical analysis of the
      exchange interactions in the VO(HPO(4)).0.5H(2)O solid is performed. Depending on
      the crystallographic structures reported in the literature, two very different
      spin models are formulated. In addition, a complete fit of the temperature
      dependent (31)P NMR chemical shift is performed to determine exchange and
      hyperfine constants. The magnetic models used in the fit are those obtained by
      our theoretical calculations. The comparison between the calculated and fitted
      exchange constants confirms the adequacy of an isolated dimer model and rules out
      the alternating antiferromagnetic chain model for VO(HPO(4)).0.5H(2)O.

PMID- 15236533
TI  - Amphiphilic ruthenium sensitizers and their applications in dye-sensitized solar
      cells.
AB  - Amphiphilic ligands 4,4'-bis(1-adamantyl-aminocarbonyl)-2,2'-bipyridine (L(1)),
      4,4'-bis[5-[N-[2-(3beta-cholest-5-en-3-ylcarbamate-N-yl)ethyl]aminocarbonyl]]
      2,2'-bipyridine (L(2)), 4,4'-bis[5-[N-[2-(3beta-cholest-5-en-3-ylcarbamate-N
      yl)propyl]aminocarbonyl]]-2,2'-bipyridine (L(3)), and 4,4'-bis(dodecan-12-ol)
      2,2'-bipyridine (L(4)) and their heteroleptic ruthenium(II) complexes of the type
      [Ru(II)LL(1)(NCS)(2)] (5), [Ru(II)LL(2)(NCS)(2)] (6), [Ru(II)LL(3)(NCS)(2)] (7),
      and [Ru(II)LL(4)(NCS)(2)] (8) (where L = 4,4'-bis(carboxylic acid)-2,2'
      bipyridine) have been synthesized starting from dichloro(p-cymene)ruthenium(II)
      dimer. All the ligands and the complexes were characterized by analytical,
      spectroscopic, and electrochemical techniques. The performance of these complexes
      as charge-transfer photosensitizers in nanocrystalline TiO(2)-based solar cells
      was studied. When complexes 5-8 anchored onto a 12 + 4 microm thick
      nanocrystalline TiO(2) films, very efficient sensitization was achieved (85 +/-
      5% incident photon-to-current efficiencies in the visible region, using an
      electrolyte consisting of 0.6 M butylmethylimidazolium iodide, 0.05 M I(2), 0.1 M
      LiI, and 0.5 M tert-butyl pyridine in 1:1 acetonitrile + valeronitrile). Under
      standard AM 1.5 sunlight, the complex 8 yielded a short-circuit photocurrent
      density of 17 +/- 0.5 mA/cm(2), the open-circuit voltage was 720 +/- 50 mV, and
      the fill factor was 0.72 +/- 0.05, corresponding to an overall conversion
      efficiency of 8.8 +/- 0.5%.

PMID- 15236534
TI  - Electron delocalization in a ruthenium(II) Bis(2,2':6',2' '-terpyridyl) complex.
AB  - Photophysical properties have been recorded for a ruthenium(II) bis(2,2':6',2' '
      terpyridine) complex bearing a single ethynylene substituent. The target compound
      is weakly emissive in fluid solution at room temperature, but both the emission
      yield and lifetime increase dramatically as the temperature is lowered. As found
      for the unsubstituted parent complex, the full temperature dependence indicates
      that the lowest-energy triplet state couples to two higher-energy triplets and to
      the ground state. Luminescence occurs only from the lowest-energy triplet state,
      but the radiative and nonradiative decay rates indicate that electron
      delocalization occurs at the triplet level. Comparison of the target compound
      with the parent complex indicates that the ethynylene group reduces the size of
      the electron-vibrational coupling element for nonradiative decay of the lowest
      energy triplet state. Although other factors are affected by substitution, this
      is by far the most important feature with regard to stabilization of the triplet
      state.

PMID- 15236535
TI  - Dinuclear nickel complexes with bidentate N,O ligands: synthesis, structure, and
      catalytic oligomerization of ethylene.
AB  - The new dicationic dinuclear complexes [Ni(micro-Cl)(2)(N,OH)(2)]Cl(2) (11, N,OH
      = 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-propan-2-ol; 12, N,OH = 2-pyridin-2-yl
      propan-2-ol) were prepared in good yields and evaluated as precatalyts in the
      oligomerization of ethylene, using MAO or AlEtCl(2) as cocatalyst. These
      paramagnetic complexes were characterized by single-crystal X-ray diffraction in
      the solid state and in solution with the help of the Evans method, which revealed
      agreement between the octahedral coordination spheres found in solution and in
      the solid state. The N donor atoms of each chelating ligand are in mutual cis
      position, and the OH donors are mutually trans situated. Selectivities for 1
      butene within the C(4) fraction of 61% (11) and 58% (12) were observed in the
      presence of 200 equiv of MAO, but better turnover frequencies (28 300 (11) and 20
      400 (12) mol of C(2)H(4)/(mol of Ni.h)) were obtained when 800 equiv of MAO was
      used. In the presence of 6 equiv of AlEtCl(2), the activities were considerably
      increased, up to 174 300 (11) and 97 100 (12) mol of C(2)H(4)/(mol of Ni.h), and
      the selectivity for C(4) olefins was 70% and 64%, respectively.

PMID- 15236536
TI  - Cyclopentadienyl ruthenium, rhodium, and iridium vertices in metallaboranes:
      geometry and chemical bonding.
AB  - Most cyclopentadienylmetallaboranes containing the vertex units CpM (M = Co, Rh,
      Ir; Cp = eta(5)-cyclopentadienyl ring, mainly eta(5)-Me(5)C(5)) and CpRu donating
      two and one skeletal electrons, respectively, have structures closely related to
      binary boranes or borane anions. Smaller clusters of this type, such as
      metallaborane analogues of arachno-B(4)H(10) (e.g., (CpIr)(2)B(2)H(8)), nido
      B(5)H(9) (e.g., (CpRh)(2)B(3)H(7) and (CpRu)(2)B(3)H(9)), arachno-B(5)H(11)
      (e.g., CpIrB(4)H(10)), B(6)H(6)(2)(-) (e.g., (CpCo)(4)B(2)H(4)), nido-B(6)H(10)
      (e.g., CpIrB(5)H(9) and (CpRu)(2)B(4)H(10)), and arachno-B(6)H(12) (e.g.,
      (CpIr)(2)B(4)H(10)), have the same skeletal electron counts as those of the
      corresponding boranes. However, such clusters with eight or more vertices, such
      as metallaborane analogues of B(8)H(8)(2)(-) (e.g., (CpCo)(4)B(4)H(4)), arachno
      B(8)H(14) (e.g., (CpRu)(2)B(6)H(12)), and nido-B(10)H(14) (e.g.,
      (CpRu)(2)B(8)H(12)), have two skeletal electrons less than those of the
      corresponding metal-free boranes, analogous to the skeletal electron counts of
      isocloso boranes relative to those of metal-free deltahedral boranes. Some
      metallaboranes have structures not analogous to metal-free boranes but instead
      analogous to metal carbonyl clusters such as 3-capped square pyramidal
      (CpRu)(2)B(4)H(8) and (CpRu)(3)B(3)H(8) analogous to H(2)Os(6)(CO)(16) and capped
      octahedral (CpRh)(3)B(4)H(4) analogous to Os(7)(CO)(21). In the metallaborane
      structures closely related to metal-free boranes, the favored degrees of BH and
      CpM vertices appear to be 5 and 6, respectively.

PMID- 15236537
TI  - Asymmetric cationic coordination environments in new oxide materials: synthesis
      and characterization of Pb(4)Te(6)M(10)O(41) (M = Nb(5+) or Ta(5+)).
AB  - Two new isostructural tellurites, Pb(4)Te(6)M(10)O(41) (M = Nb(5+) or Ta(5+)),
      have been synthesized by standard solid-state techniques using PbO, Nb(2)O(5) (or
      Ta(2)O(5)), and TeO(2) as reagents. The structures of Pb(4)Te(6)Nb(10)O(41) and
      Pb(4)Te(6)Ta(10)O(41) were determined by single-crystal and powder X-ray
      diffraction. The materials exhibit a three-dimensional framework consisting of
      layers of corner-shared NbO(6) octahedra connected by TeO(3) and PbO(6)
      polyhedra. The Nb(5+), Te(4+), and Pb(2+) cations are in asymmetric coordination
      environments attributable to second-order Jahn-Teller effects. The Nb(5+) cations
      undergo an intraoctahedral distortion either toward a face or a corner, whereas
      the Te(4+) and Pb(2+) cations are in distorted environments attributable to their
      lone pair. In addition, the TeO(3) polyhedra strongly influence the direction of
      the Nb(5+) intraoctahedral distortion. Infrared and Raman spectroscopy,
      thermogravimetric analysis, and dielectric measurements are also presented.
      Crystal data: Pb(4)Te(6)Nb(10)O(41), monoclinic, space group C2/m (No. 12), with
      a = 23.412(3) A, b = 20.114(3) A, c = 7.5008(10) A, beta = 99.630(4) degrees, V =
      3482.4(8) A(3), and Z = 4; Pb(4)Te(6)Ta(10)O(41), monoclinic, space group C2/m
      (No. 12), with a = 23.340(8) A, b = 20.068(5) A, c = 7.472(2) A, beta = 99.27(3)
      degrees, V = 3453.8(2) A(3), and Z = 4.

PMID- 15236538
TI  - Crystal growth, observation, and characterization of the low-temperature
      structure of the fluorite-related ruthenates: Sm(3)RuO(7) and Eu(3)RuO(7).
AB  - The compounds Sm(3)RuO(7) and Eu(3)RuO(7) were grown as single crystals from
      molten hydroxide fluxes. They crystallize in the orthorhombic space group Cmcm
      and are part of a well-known family of fluorite-related oxides of stoichiometry
      Ln(3)MO(7). This structure contains rare earth cations in two different
      coordination environments, 8-fold pseudocubic and 7-fold pentagonal bipyramidal,
      and contains Ru(V) cations that are octahedrally coordinated. The RuO(6)
      octahedra are trans vertex-sharing to yield chains oriented along the c-axis.
      Upon cooling, single crystals of Sm(3)RuO(7) and Eu(3)RuO(7) undergo a structural
      transition at 190 and 280 K, respectively, from space group Cmcm to P2(1)nb. The
      structure transition results in a loss of lattice centering, a doubling of the b
      axis, a distortion of the vertex-shared Ru-O chains, and a reduction in the
      coordination of one of the rare earth cations from 8-fold to 7-fold. Accompanying
      this structural transition are anomalies in the magnetic susceptibility at about
      190 and 280 K for Sm(3)RuO(7) and Eu(3)RuO(7), respectively. The structures of
      these low-temperature phases of Ln(3)RuO(7) have been determined for the first
      time and are described.

PMID- 15236539
TI  - cis-[Ru(2,2':6',2' '-terpyridine)(DMSO)Cl(2)]: useful precursor for the synthesis
      of heteroleptic terpyridine complexes under mild conditions.
AB  - [Ru(II)(terpy)(DMSO)Cl(2)] complexes were synthesized as a 5/1 mixture of cis and
      trans isomers, and their reactivities with CO and with substituted 2,2':6',2' '
      terpyridine (terpy) moieties have been investigated. The structure of a trans
      isomer and its CO adduct have been unambiguously assigned by spectroscopy and X
      ray diffraction. The [Ru(terpy)(terpy-Br)](2+) complex prepared either from the
      cis-[Ru(II)(terpy)(DMSO)Cl(2)] or from the cis-[Ru(II)(terpy-Br)(DMSO)Cl(2)]
      precursor appeared to be reactive in cross-coupling reactions promoted by low
      valent palladium(0) and is an attractive target for the stepwise synthesis of
      polynuclear complexes bearing vacant coordination sites (terpy-Br for 4'-bromo
      2,2':6',2' '-terpyridine). Several bipyridine, phenanthroline, and bipyrimidine
      complexes were prepared this way and their optical and redox properties
      determined and discussed.

PMID- 15236540
TI  - Lead and thallium tetrakis(imidazolyl)borates: modifying structure by varying
      metal and anion.
AB  - We are using the coordinating anions tetrakis(imidazolyl)borate and tetrakis(4
      methylimidazolyl)borate to construct new metal-organic framework structures. In
      this report, we are exploring materials similar in composition to the previously
      reported layered network structure Pb[B(Im)(4)](NO(3))(nH(2)O). The metal in this
      compound can be replaced with isoelectronic Tl(I), affording Tl[B(Im)(4)], and
      the borate can be modified by using 4-methylimidazole, resulting in Pb[B(4
      MeIm)(4)](NO(3)) and Tl[B(4-MeIm)(4)]. Like the parent
      Pb[B(Im)(4)](NO(3))(nH(2)O), Tl[B(Im)(4)] and Tl[B(4-MeIm)(4)] are layered
      network structures but both lack anions or solvent molecules in the interlayer
      spacing. The material Pb[B(4-MeIm)(4)](NO(3)), however, exhibits a 3D network
      structure that lacks an open topology, resulting from the increased
      stereochemical activity (greater steric bulk toward other ligands) of the 4
      methylimidazole ring. Both of the Tl(I) solids display longer M-N bonds than
      observed in the analogous Pb(II) compounds; these lengths account for the
      decreased effect of the stereochemical activity of the 4-methylimidazole ring in
      Tl[B(4-MeIm)(4)].

PMID- 15236541
TI  - Copper(II) complexes of a series of alkoxy diazine ligands: mononuclear,
      dinuclear, and tetranuclear examples with structural, magnetic, and DFT studies.
AB  - Picolyl hydrazide ligands have two potentially bridging functional groups (micro
      O, micro-N-N) and consequently can exist in different coordination conformers,
      both of which form spin-coupled polynuclear coordination complexes, with quite
      different magnetic properties. The complex [Cu(2)(POAP-H)Br(3)(H(2)O)] (1)
      involves a micro-N-N bridge (Cu-N-N-Cu 150.6 degrees ) and exhibits quite strong
      antiferromagnetic coupling (-2J = 246(1) cm(-)(1)). [Cu(2)(PZOAPZ
      H)Br(3)(H(2)O)(2)] (2) has two Cu(II) centers bridged by an alkoxide group with a
      very large Cu-O-Cu angle of 141.7 degrees but unexpectedly exhibits quite weak
      antiferromagnetic exchange (-2J = 91.5 cm(-)(1)). This is much weaker than
      anticipated, despite direct overlap of the copper magnetic orbitals. Density
      functional calculations have been carried out on compound 2, yielding a similar
      singlet-triplet splitting energy. Structural details are reported for [Cu(2)(POAP
      H)Br(3)(H(2)O)] (1), [Cu(2)(PZOAPZ-H)Br(3)(H(2)O)(2)] (2), [Cu(2)(PAOPF
      2H)Br(2)(DMSO)(H(2)O)].H(2)O (3), [Cu(4)(POMP-H))(4)](NO(3))(4).2H(2)O (4), and
      PPOCCO (5) (a picolyl hydrazide ligand with a terminal oxime group) and its
      mononuclear complexes [Cu(PPOCCO-H)(NO(3))] (6) and [Cu(PPOCCO-H)Cl] (7).
      Compound 1 (C(12)H(13)Br(3)Cu(2)N(5)O(4)) crystallizes in the monoclinic system,
      space group P2(1)/c, with a = 15.1465(3) A, b = 18.1848(12) A, c = 6.8557(5) A,
      beta = 92.751(4) degrees, and Z = 4. Compound 2 (C(10)H(13)Br(3)Cu(2)N(7)O(4))
      crystallizes in the triclinic system, space group P, with a = 9.14130(1) A, b =
      10.4723(1) A, c = 10.9411(1) A, alpha = 100.769(1), beta = 106.271(1) degrees,
      gamma = 103.447(1) degrees, and Z = 2. Compound 3
      (C(23)H(22)Br(2)Cu(2)N(7)O(5.5)S) crystallizes in the monoclinic system, space
      group P2(1)/c, with a = 12.406(2) A, b = 22.157(3) A, c = 10.704(2) A, beta =
      106.21(1) degrees, and Z = 4. Compound 4(C(52)H(48)Cu(4)N(20)O(18)) crystallizes
      in the monoclinic system, space group P2(1)/n, with a = 14.4439(6) A, b =
      12.8079(5) A, c = 16.4240(7) A, beta = 105.199(1) degrees, and Z = 4. Compound 5
      (C(15)H(14)N(4)O(2)) crystallizes in the orthorhombic system, space group
      Pna2(1), with a = 7.834(3) A, b = 11.797(4) A, c = 15.281(3) A, and Z = 4.
      Compound 6(C(15)H(13)CuN(5)O(5)) crystallizes in the monoclinic system, space
      group P2(1)/c, with a = 8.2818(9) A, b = 17.886(2) A, c = 10.828(1) A, beta =
      92.734(2) degrees, and Z = 4. Compound 7 (C(15)H(13)CuClN(4)O(2)) crystallizes in
      the orthorhombic system, space group Pna2(1), with a = 7.9487(6) A, b =
      14.3336(10) A, c = 13.0014(9) A, and Z = 4. Density functional calculations on
      PPOCCO are examined in relation to the anti-eclipsed conformational change that
      occurs on coordination to copper(II).

PMID- 15236542
TI  - Molecular structure and vibrational spectra of spin-crossover complexes in
      solution and colloidal media: resonance Raman and time-resolved resonance Raman
      studies.
AB  - The spin-crossover system [Fe(btpa)](PF(6))(2) (btpa = N,N,N',N'-tetrakis(2
      pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'-bipyridine) and the predominantly low
      spin species [Fe(b(bdpa))](PF(6))(2) ((b(bdpa) = N,N'-bis(benzyl)-N,N'-bis(2
      pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'-bipyridine) have been characterized by
      means of X-ray diffraction. The unit cell of [Fe(btpa)](PF(6))(2) contains two
      crystallographically independent molecules revealing octahedral low-spin and
      quasi-seven-coordinated high-spin structures. The unit cell of
      [Fe(b(bdpa))](PF(6))(2) contains two crystallographically independent molecules
      one of which corresponds to a low-spin structure, while the other reveals a
      disordering. On the basis of magnetic susceptibility and Mossbauer measurements,
      it has been proposed that this disorder involves low-spin and high-spin six
      coordinated molecules. The structures of [Zn(btpa)](PF(6))(2) and
      [Ru(btpa)](PF(6))(2) have been determined also. Pulsed laser photoperturbation,
      coupled here with time-resolved resonance Raman spectroscopy (TR(3)), has been
      used to investigate, for the first time by this technique, the relaxation
      dynamics in solution on nanosecond and picosecond time scales of low-spin, LS
      ((1)A) --> high-spin, HS ((5)T) electronic spin-state crossover in these Fe(II)
      complexes. For the nanosecond experiments, use of a probe wavelength at 321 nm,
      falling within the pi-pi transition of the polypyridyl backbone of the ligands,
      enabled the investigation of vibrational modes of both LS and HS isomers, through
      coupling to spin-state-dependent angle changes of the backbone. Supplementary
      investigations of the spin-crossover (SCO) equilibrium in homogeneous solution
      and in colloidal media assisted the assignment of prominent features in the Raman
      spectra of the LS and HS isomers. The relaxation data from the nanosecond studies
      confirm and extend earlier spectrophotometric findings, (Schenker, S.; Stein, P.
      C.; Wolny, J. A.; Brady, C.; McGarvey, J. J.; Toftlund, H.; Hauser, A. Inorg.
      Chem. 2001, 40, 134), pointing to biphasic spin-state relaxation in the case of
      [Fe(btpa)](PF(6))(2) but monophasic in the case of [Fe(b(bdpa))](PF(6))(2). The
      picosecond results suggest an early process complete in 20 ps or less, which is
      common to both complexes and possibly includes vibrational relaxation in the
      initially formed (5)T(2) state.

PMID- 15236543
TI  - Influence of the [2.1.1]-(2,6)-pyridinophane macrocycle ring size constraint on
      the structure and reactivity of copper complexes.
AB  - The macrocycle [2.1.1]-(2,6)-pyridinophane (L) binds to CuCl to give a monomeric
      molecule with tridentate binding of the ligand but in a distorted tetrahedral "3
      + 1" geometry, where one nitrogen forms a longer (by 0.12 A) bond to Cu. In
      dichloromethane solvent this pyridine donor undergoes facile site exchange with a
      second pyridine in the macrocycle, to give time-averaged mirror symmetry. Both
      experimental and density functional theory studies of the product of chloride
      abstraction, using NaBAr(F)(4) in CH(2)Cl(2), show that the Cu(+) binds in a
      trigonal pyramidal, not planar, arrangement in LCu(+). This illustrates the
      ability of macrocyclic ligand constraint to impose an electronically unfavorable
      geometry on 3-coordinate Cu(I). LCuBAr(F)(4) and a triflate analogue LCu(I)(OTf)
      readily react with oxygen in dichloromethane to produce, in the latter case, a
      hydroxo-bridged dimer [LCu(II)(micro-OH)](2)(OTf)(2), of the intact (unoxidized)
      ligand L. Since the analogous LCuCl does not react as fast with O(2) in
      CH(2)Cl(2), outer-sphere electron transfer is concluded to be ineffective for
      oxidation of cuprous ion here.

PMID- 15236544
TI  - A nonacoordinated bridging selenide in a tricapped trigonal prismatic geometry
      identified in undecanuclear copper clusters: syntheses, structures, and DFT
      calculations.
AB  - Undecanuclear copper clusters, [Cu(11)(micro(9)-Se)(micro(3)
      Br)(3)[Se(2)P(OR)(2)](6)] (R = Et, Pr, (i)Pr) (1a-c), were isolated along with
      closed-shell ion-centered cubes, [Cu(8)(micro(8)-Br)[Se(2)P(OR)(2)](6)] (PF(6))
      (2a-c) and [Cu(8)(micro(8)-Se)[Se(2)P(OR)(2)](6)] (3a-c), from the reaction of
      [Cu(CH(3)CN)(4)](PF(6)), NH(4)[Se(2)P(OR)(2)], and Bu(4)NBr in a molar ratio of
      2:3:2 in CH(2)Br(2). The molecular formulations of these clusters were confirmed
      by elemental analysis, positive FAB mass spectrometry, and multinuclear NMR
      ((1)H, (31)P, and (77)Se). (77)Se NMR spectra of Cu(11) clusters (1a-c) are of
      special interest as two inequivalent selenium nuclei of the diselenophosphate
      (dsep) ligand exhibit different scalar coupling patterns with the adjacent
      phosphorus nuclei. X-ray analysis of 1c reveals a Cu(11)Se core stabilized by
      three bromide and six dsep ligands. The central core adopts the geometry of a
      3,3,4,4,4-pentacapped trigonal prism with a selenium atom in the center. The
      coordination geometry for the nonacoordinate selenium atom is tricapped trigonal
      prismatic. The X-ray structure 2a or 2c consists of a cationic cluster in which
      eight copper ions are linked by six diselenophosphate ligands with a central
      micro(8)-Br ion. The shape of the molecule is a bromide-centered distorted Cu(8)
      cube. Each diselenophosphate ligand occupies square faces of the cube and adopts
      a tetrametallic tetraconnective coordination pattern. Each copper atom of the
      cube is coordinated by three selenium atoms with a strong interaction with the
      central bromide ion. Molecular orbital calculations at the B3LYP level of the
      density functional theory have been carried out to study the Cu-micro(9)-Se
      interactions for clusters [Cu(11)(micro(9)-Se)(micro(3)-X)(3)[Se(2)P(OR)(2)](6)]
      (X = Br, I). Calculations show that the formal bond order of each Cu-micro(9)-Se
      bond is slightly smaller than half of those calculated for the terminal Cu
      micro(2)-Se bonds.

PMID- 15236545
TI  - (Salen)tin complexes: syntheses, characterization, crystal structures, and
      catalytic activity in the formation of propylene carbonate from CO(2) and
      propylene oxide.
AB  - A series of (salen)tin(II) and (salen)tin(IV) complexes was synthesized. The
      (salen)tin(IV) complexes, (salen)SnX(2) (X = Br and I), were prepared in good
      yields via the direct oxidation reaction of (salen)tin(II) complexes with Br(2)
      or I(2). (Salen)SnX(2) successfully underwent the anion-exchange reaction with
      AgOTf (OTf = trifluoromethanesulfonate) to form (salen)Sn(OTf)(2) and
      (salen)Sn(X)(OTf) (X = Br). The (salen)Sn(OTf)(2) complex was easily converted to
      any of the dihalide (salen)SnX(2) compounds using halide salts. All complexes
      were fully characterized by (1)H NMR spectroscopy, mass spectrometry, and
      elemental analysis, while some were characterized by (13)C, (19)F, and (119)Sn
      NMR spectroscopy. Several crystal structures of (salen)tin(II) and (salen)tin(IV)
      were also determined. Finally, both (salen)tin(II) and (salen)tin(IV) complexes
      were shown to efficiently catalyze the formation of propylene carbonate from
      propylene oxide and CO(2). Of the series, (3,3',5,5'-Br(4)-salen)SnBr(2), 3i, was
      found to be the most effective catalyst (TOF = 524 h(-)(1)).

PMID- 15236546
TI  - Modification of binuclear Pt-Tl bonded complexes by attaching bipyridine ligands
      to the thallium site.
AB  - Complex formation of monomeric thallium(III) species with 2,2'-bipyridine (bipy)
      in dimethyl sulfoxide (dmso) and acetonitrile solutions was studied by means of
      multinuclear ((1)H, (13)C, and (205)Tl) NMR spectroscopy. For the first time, NMR
      signals of the individual species [Tl(bipy)(m)(solv)](3+) (m = 1-3) were observed
      despite intensive ligand and solvent exchange processes. The tris(bipy) complex
      was crystallized as [Tl(bipy)(3)(dmso)](ClO(4))(3)(dmso)(2) (1), and its crystal
      structure determined. In this compound, thallium is seven-coordinated; it is
      bonded to six nitrogen atoms of the three bipy molecules and to an oxygen atom of
      dmso. Metal-metal bonded binuclear complexes [(NC)(5)Pt-Tl(CN)(n)(solv)](n)(-) (n
      = 0-3) have been modified by attaching bipy molecules to the thallium atom. A
      reaction between [(NC)(5)Pt-Tl(dmso)(4)](s) and 2,2'-bipyridine in dimethyl
      sulfoxide solution results in the formation of a new complex, [(NC)(5)Pt
      Tl(bipy)(solv)]. The presence of a direct Pt-Tl bond in the complex is
      convincingly confirmed by a very strong one-bond (195)Pt-(205)Tl spin-spin
      coupling ((1)J((195)Pt-(205)Tl) = 64.9 kHz) detected in both (195)Pt and (205)Tl
      NMR spectra. In solutions containing free cyanide, coordination of CN(-) to the
      thallium atom occurs, and the complex [(NC)(5)Pt-Tl(bipy)(CN)(solv)](-)
      ((1)J((195)Pt-(205)Tl) = 50.1 kHz) is formed as well. Two metal-metal bonded
      compounds containing bipy as a ligand were crystallized and their structures
      determined by X-ray diffractometry: [(NC)(5)Pt-Tl(bipy)(dmso)(3)] (2) and
      [(NC)(5)Pt-Tl(bipy)(2)] (3). The Pt-Tl bonding distances in the compounds,
      2.6187(7) and 2.6117(5) A, respectively, are among the shortest reported
      separations between these two metals. The corresponding force constants in the
      molecules, 1.38 and 1.68 N/cm, respectively, were calculated using Raman
      stretching frequencies of the Pt-Tl vibrations and are characteristic for a
      single metal-metal bond. Electronic absorption spectra were recorded for the
      [(NC)(5)Pt-Tl(bipy)(m)(solv)] compounds, and the optical transition was
      attributed to the metal-metal bond assigned.

PMID- 15236547
TI  - NMR and EPR spectroscopic and structural studies of low-spin,
      (d(xz),d(y)(z))(4)(d(x)(y))(1) ground state Fe(III) bis-tert-butylisocyanide
      complexes of dodecasubstituted porphyrins.
AB  - The bis-(1,1-dimethylethylisocyanide) (tert-butylisocyanide) complexes of three
      iron porphyrinates (2,3,7,8,12,13,17,18-octaethyl-5,10,15,20
      tetraphenylporphyrin, OETPP; 2,3,7,8,12,13,17,18-octamethyl-5,10,15,20
      tetraphenylporphyrin, OMTPP; and 2,3,7,8,12,13,17,18-tetra-beta,beta'
      tetramethylene-5,10,15,20-tetraphenylporphyrin, TC(6)TPP) have been prepared and
      studied by EPR and (1)H NMR spectroscopy. From EPR and NMR spectroscopic results
      it has been found that the ground states of the bis-(t-BuNC) complexes of OETPP,
      OMTPP, and TC(6)TPP are represented mainly (99.1-99.4%) as
      (d(xz,)d(yz))(4)(d(xy))(1) electron configurations, with an excited state lying
      700 cm(-)(1) to higher energy for the OMTPP complex, and probably at lower and
      higher energies, respectively, for the OETPP and TC(6)TPP complexes. In the (1)H
      NMR spectra the (d(xz,)d(yz))(4)(d(xy))(1) electron configurations of all three
      complexes are indicated by the large and positive meso-phenyl-H shift
      differences, delta(m)-delta(o) and delta(m)-delta(p), and close to the
      diamagnetic shifts of groups (CH(3) or CH(2)) directly attached to the beta
      carbons. However, in comparison to meso-only substituted porphyrinates such as
      [FeTPP(t-BuNC)(2)]ClO(4), the meso-phenyl shift differences are much smaller,
      especially for the OETPP complex. 2D NOESY spectra show that the flexibility of
      the porphyrin core decreases with increasing nonplanar distortion in the order
      TC(6)TPP > OMTPP > OETPP and in the same order the stability of the binding to t
      BuNC ligands decreases. In addition, the structures of two crystalline forms of
      [FeOMTPP(t-BuNC)(2)]ClO(4) have been determined by X-ray crystallography. Both
      structures showed purely saddled porphyrin cores and somewhat off-axis binding of
      the isocyanide ligands. To our knowledge, this is the first example of a
      porphyrin complex with a purely saddled conformation that adopts the
      (d(xz,)d(yz))(4)(d(xy))(1) ground state. All structurally-characterized complexes
      of this electron configuration reported previously are ruffled. Therefore, we
      conclude that a ruffled geometry stabilizes the (d(xz,)d(yz))(4)(d(xy))(1) ground
      state, but is not necessary for its existence.

PMID- 15236548
TI  - Synthesis and reactivity of tris(imido)rhenium complexes containing rhenium-main
      group element bonds. silicon-carbon bond activations of PhSiH(3) by silyl
      complexes.
AB  - The synthesis and reactivity of a series of complexes of the (DippN=)(3)Re (Dipp
      = 2,6-(i)Pr(2)C(6)H(3)) fragment are reported. The anionic, Re(V) complex
      (THF)(2)Li(micro,micro-NDipp)(2)Re(=NDipp) (1), prepared by the reaction of
      (DippN=)(3)ReCl with (THF)(3)LiSi(SiMe(3))(3) or (t)BuLi (2 equiv) in the
      presence of THF (4 equiv), served as an important starting material for the
      synthesis of rhenium-element-bonded complexes. For example, treatment of 1 with
      ClSiR(3) gave the corresponding silyl complexes (DippN=)(3)ReSiR(3) (SiR(3) =
      SiMe(3) (2a), SiHPh(2) (2b), SiH(2)Ph (2c)). Complexes 2a-c are thought to exist
      in equilibrium between the Re(VII) (DippN=)(3)ReSiR(3) and Re(V)
      (DippN=)(2)ReN(SiR(3))Dipp isomers. Complexes 2a,b reacted with PhSiH(3) to give
      reaction mixtures that included 2c, Ph(2)SiH(2), SiH(4), and C(6)H(6). The silane
      and organic products arise from Si-C bond formation and cleavage. Treatment of 2a
      with CO gave (DippN=)(2)Re[N(SiMe(3))Dipp](CO) (3), which appears to result from
      trapping of the reactive Re(V) isomer of 2a by CO. Complex 1 reacted with the
      main group halides MeI, Ph(3)GeCl, Me(3)SnCl, Ph(2)PCl, and PhSeCl to give the
      corresponding rhenium complexes (DippN=)(3)ReER(n) (ER(n)() = Me (4), GePh(3)
      (5), SnMe(3) (6), PPh(2) (7), SePh (8)) in high yields. X-ray diffraction data
      for 5 indicate that the germyl ligand is bonded to rhenium, but positional
      disorder of the phenyl and Dipp groups prevented refinement of accurate metric
      parameters.

PMID- 15236549
TI  - Spectroscopic and structural study of metal-metal bonded metalloporphyrinic
      derivatives: the case of rhodium-indium.
AB  - The synthesis and spectroscopic characterization of heterometallic porphyrinate
      derivatives containing rhodium-indium metal-metal bonds are reported. The
      investigated compounds are represented by the formula [(Porph)RhIn(Porph')],
      where Porph and Porph' are OEP, TPP, beta-Cl(4)TPP, beta-Cl(8)TPP, or TPyP. UV
      Visible spectroscopy of the title complexes confirms the presence of a strong pi
      pi interaction between the macrocycles in each derivative and denotes the effect
      of the nontransition metal in their optical features. For comparison purposes, a
      new bimetallic complex with a rhodium-thallium metal-metal bond is also
      presented. According to (1)H and (13)C NMR data, we were able to distinguish two
      major NMR regions: the endo- between the metal-metal bonded macrocycles and the
      exo-, which are characteristic features of porphyrinic complexes at very close
      proximity. X-ray absorption spectroscopy (XAS) structural characterization of Rh
      In bond was performed on the [(OEP)RhIn(OEP)] complex, in the fluorescence mode,
      and we essentially focused on the metal-metal distance determination. Finally,
      the distance of 2.543(3) A was deduced from the X-ray structure of a new
      [(TPP)RhIn(TPyP)] derivative.

PMID- 15236550
TI  - Six-membered metalla-coronands. synthesis and crystal packing: columns,
      compartments, and 3D-networks.
AB  - Reaction of various N-substituted diethanolamines H(2)L(3) (4) with calcium
      hydride and iron(III) chloride leads to the self-assembly of six-membered ferric
      wheels [Fe(6)X(6)(L(3))(6)] (5). Principally, all the iron coronands are
      isostructural; however, they differ fundamentally with respect to their crystal
      packing. Exemplarily, this is discussed for selected members of the space groups
      R, P, P2(1)/c, P2(1)/n, C2/c, and P. Depending on the nature of their sidearms,
      the ferric wheels create various substructures. For instance, the ferric wheels
      5a-i of space group R or P are piled in parallel in cylindrical columns, which
      are surrounded by six parallel columns alternately dislocated by (1)/(3)c and
      (2)/(3)c against the central one. Pronounced van der Waals interactions give rise
      to compartmentation and incarceration of guest molecules as seen for 5e,g.
      However, in 5h strong pi-pi interactions create a three-dimensional scaffold. The
      most significant difference of the ferric wheels 5j-p of space groups P2(1)/c,
      P2(1)/n, and C2/c is that these ferric wheels are arranged in parallel in two
      orientations. They differ mainly only by the included angle of the two groups of
      parallel wheels. In the case of 5l, molecular chains are formed in the crystal
      due to pi-pi interactions. The ferric wheels 5q-y of space group P are packed in
      the crystal most simply, with all the ferric wheels piled in parallel.

PMID- 15236551
TI  - Unusual enlargment of magnetic interactions in the lowest excited states of
      nitroxide radical chromium(III) complexes as revealed by magnetic circular
      dichroism and luminescence.
AB  - Magnetic circular dichroism and NIR luminescence of nitroxide radical complexes,
      [Cr(III)(beta-diketonato)(2)(NIT2py or IM2py)]PF(6), demonstrate that the energy
      gaps between the singlet ((1)L(D)) and triplet ((3)L(D)) spin coupled levels in
      the lowest excited (2)E(g),(2)T(1g) states are much larger than those in the
      ground state. This is the first observation of magnetic interactions in the
      excited states of radical complexes, which could be elucidated in terms of the
      exchange mechanism.

PMID- 15236552
TI  - Silver coordination chemistry of a new versatile "Janus"-type N(2),O(2)
      bichelating donor, formation of an unprecedented supramolecular network of
      binuclear silver building blocks containing a five-coordinate beta-diketonate,
      and isolation of unexpected silver-tin-silver heterotrimetallic complexes from
      silver metathesis reactions.
AB  - Synthetic, spectroscopic, and single-crystal X-ray studies are reported for
      several complexes of silver(I) with the N(2),O(2)-bichelating Q(py) ligand
      (HQ(py) = 1-(2-pyridyl)-3-methyl-4-trifluoroacetylpyrazol-5-one). Direct
      interaction between HQ(py) and AgNO(3) in methanol, in the presence of NaOCH(3),
      affords derivative Ag(Q(py)), showing a polynuclear structure composed of
      dinuclear building blocks with two different Ag environments and two Q(py) donors
      differently connected. By adding neutral ligands such as PR(3) (R = Ph, Cy,
      C(6)H(4)-o-CH(3), C(6)H(4)-p-F, Bu(i)) to Ag(Q(py)), dinuclear Ag(Q(py))(PR(3))
      derivatives have been isolated, containing bridging N(2),O-exotridentate Q(py)
      donors spanning a pair of AgPR(3) moieties. Reaction of Ag(Q(py))(PPh(3)) with
      excess PPh(3) produces the mononuclear Ag(Q(py))(PPh(3))(2) containing N(2)
      chelate Q(py). Ag(Q(py)) interacts with 1,2-bis(diphenylphosphino)ethane (dppe)
      yielding the derivative Ag(Q(py))(dppe), having a polynuclear structure in the
      solid state which is seemingly disrupted in solution, with the formation of two
      new species, a mononuclear neutral compound and a dinuclear ionic one. By the
      interaction of Ag(Q(py)) with nitrogen donors L (L = imidazole (imH), 1
      methylimidazole (Meim), 1-methyl-2-mercaptoimidazole (Hmimt), 1,10-phenanthroline
      (phen)), mononuclear species Ag(Q(py))(L) have been obtained, where Q(py) is
      coordinated to silver in N(2)-chelating mode. Ag(Q(py))(PPh(3))(2) reacts with
      SnRCl(3) (R = Ph, Bu(n)) affording heterotrimetallic
      [[(Ph(3)P)(2)AgCl](2)SnRCl(3)] derivatives.

PMID- 15236553
TI  - Zr(7)Sb(4): a new binary zirconium-rich antimonide.
AB  - Zr(7)Sb(4) has been prepared by arc-melting of the elemental components and
      annealing at 1000-1150 degrees C. Its crystal structure was determined by X-ray
      diffraction (Pearson symbol mP44, monoclinic, space group P2(1)/c, Z = 4, a =
      8.4905(6) A, b = 11.1557(8) A, c = 11.1217(8) A, beta = 111.443(2) degrees at 295
      K). Zr(7)Sb(4) is isotypic to Hf(6)TiSb(4), a compound stabilized by differential
      fractional site occupancy. It is the first binary group-4 antimonide with this
      metal-to-antimony ratio, but it differs from the corresponding phosphides and
      arsenides M(7)Pn(4) (M = Ti, Zr, Hf; Pn = P, As), which adopt the Nb(7)P(4)-type
      structure. Zr(7)Sb(4) is built up from layers excised from the tetragonal
      W(5)Si(3)-type structure; these layers are displaced relative to each other to
      maximize interlayer Zr-Zr and Zr-Sb bonding, as confirmed by band structure
      calculations.

PMID- 15236554
TI  - Sulfur-bridged Co(III)Pt(II)Co(III) trinuclear complexes with mixed aliphatic and
      aromatic thiolate ligands: effect of nonbridging ligands on the homochiral
      linkage of cobalt(III) octahedrons by platinum(II).
AB  - The reaction of [Ni[Co(aet)(2)(pyt)](2)](2+) (aet = 2-aminoethanethiolate, pyt =
      2-pyridinethiolate) with [PtCl(4)](2)(-) gave an S-bridged Co(III)Pt(II)Co(III)
      trinuclear complex composed of two [Co(aet)(2)(pyt)] units,
      [Pt[Co(aet)(2)(pyt)](2)](2+) ([1](2+)). When a 1:1 mixture of
      [Ni[Co(aet)(2)(pyt)](2)](2+) and [Ni[Co(aet)(2)(en)](2)](4+) was reacted with
      [PtCl(4)](2)(-), a mixed-type S-bridged Co(III)Pt(II)Co(III) complex composed of
      one [Co(aet)(2)(pyt)] and one [Co(aet)(2)(en)](+) units,
      [Pt[Co(aet)(2)(en)][Co(aet)(2)(pyt)]](3+) ([2](3+)), was produced, together with
      [1](2+) and [Pt[Co(aet)(2)(en)](2)](4+). The corresponding Co(III)Pt(II)Co(III)
      trinuclear complexes containing pymt (2-pyrimidinethiolate),
      [Pt[Co(aet)(2)(pymt)](2)](2+) ([3](2+)) and
      [Pt[Co(aet)(2)(en)][Co(aet)(2)(pymt)]](3+) ([4](3+)), were also obtained by
      similar reactions, using [Ni[Co(aet)(2)(pymt)](2)](2+) instead of
      [Ni[Co(aet)(2)(pyt)](2)](2+). While [Pt[Co(aet)(2)(en)](2)](4+) formed both the
      deltalambda (meso) and deltadelta/lambdalambda (racemic) forms in a ratio of ca.
      1:1, the preferential formation of the deltadelta/lambdalambda form was observed
      for [1](2+) (ca. deltalambda:deltadelta/lambdalambda = 1:3) and [2](3+) (ca.
      delta(en)lambda(pyt)/lambda(en)delta(pyt):deltadelta/lambdalambda = 1:2).
      Furthermore, [3](2+) and [4](3+) predominantly formed the deltadelta/lambdalambda
      form. These results indicate that the homochiral selectivity for the S-bridged
      Co(III)Pt(II)Co(III) trinuclear complexes composed of two octahedral
      [Co(aet)(2)(L)](0 or +) units is enhanced in the order L = en < pyt < pymt. The
      isomers produced were separated and optically resolved, and the crystal
      structures of the meso-type deltalambda-[1]Cl(2).4H(2)O and the spontaneously
      resolved deltadelta-[4](ClO(4))(3).H(2)O were determined by X-ray analyses. In
      deltalambda-[1](2+), the delta and Lambda configurational mer(S).trans(N(aet))
      [Co(aet)(2)(pyt)] units are linked by a square-planar Pt(II) ion through four aet
      S atoms to form a linear-type S-bridged trinuclear structure. In deltadelta
      [4](3+), a similar linear-type trinuclear structure is constructed from the delta
      mer(S).trans(N(aet))-[Co(aet)(2)(pymt)] and delta-C(2)-cis(S)-[Co(aet)(2)(en)](+)
      units that are bound by a Pt(II) ion with a slightly distorted square-planar
      geometry through four aet S atoms.

PMID- 15236555
TI  - Controlled redox conversion of new X-ray-Characterized Mono- and dinuclear
      heptacoordinated Mn(II) complexes into di-micro-oxo-dimanganese core complexes.
AB  - Two heptacoordinated Mn(II) complexes are isolated and X-ray characterized using
      the well-known tpen ligand (tpen = N,N,N',N'-tetrakis(2-pyridylmethyl)-1,2
      ethanediamine): [(tpen)Mn(OH(2))](ClO(4))(2) (1(ClO(4))(2)) and [(tpen)Mn(micro
      OAc)Mn(tpen)](ClO(4))(3).2H(2)O (2(ClO(4))(3).2H(2)O). Crystallographic data for
      1(ClO(4))(2) at 110(2) K (respectively at 293(2) K): monoclinic, space group
      C2/c, a = 15.049(3) A (15.096(3) A), b = 9.932(2) A (10.105(2) A), c = 19.246(4)
      A (19.443(4) A), beta = 94.21(3) degrees (94.50(3) degrees ), Z = 4.
      Crystallographic data for 2(ClO(4))(3).0.5(C(2)H(5))(2)O at 123(2) K: triclinic,
      space group P, a = 12.707(3) A, b = 12.824(3) A, c = 19.052(4) A, alpha =
      102.71(3) degrees, beta = 97.83(3) degrees, gamma = 98.15(3) degrees, Z = 2.
      Investigation of the variation upon temperature of the molar magnetic
      susceptibility of compound 2(ClO(4))(3).2H(2)O reveals a weak antiferromagnetic
      exchange interaction between the two high-spin Mn(II) ions (J = -0.65 +/- 0.05
      cm(-)(1), H = -JS(1).S(2)). EPR spectra are recorded on powder samples and on
      frozen acetonitrile solutions, demonstrating the maintenance upon dissolution of
      the heptacoordination of Mn in complex 1 while complex 2 partially dissociates.
      Electrochemical responses of complexes 1 and 2 are investigated in acetonitrile,
      and bulk electrolyses are performed at oxidative potential in the presence of
      various amounts of 2,6-lutidine (0-2.65 equiv per Mn ion). The formation from
      either 1 or 2 of the mixed-valent complex [(tpen)Mn(III)(micro
      O)(2)Mn(IV)(tpen)](3+) (3) is established from mass spectrometry and EPR and IR
      spectroscopy measurements. When reaction is started from 2, formation of
      [(tpen)Mn(IV)(micro-O)(2)(micro-OAc)Mn(IV)](3+) (4) is evidenced from cyclic
      voltammetry, EPR, and UV-vis data. The Mn vs tpen ratio in the electrogenerated
      complexes is accurately controlled by the quantity of additional 2,6-lutidine.
      The role of tpen as a base is discussed.

PMID- 15236556
TI  - Catalytic oxidative ring opening of THF promoted by a carboxylate-bridged diiron
      complex, triarylphosphines, and dioxygen.
AB  - The catalytic oxidation of triphenylphosphine in the presence of dioxygen by the
      diiron(II) complex [Fe(2)(micro-O(2)CAr(Tol))(2)(Me(3)TACN)(2)(MeCN)(2)](OTf)(2)
      (1), where (-)O(2)CAr(Tol) = 2,6-di(p-tolyl)benzoate and Me(3)TACN = 1,4,7
      trimethyl-1,4,7-triazacyclononane, has been investigated. The corresponding
      diiron(III) complex, [Fe(2)(micro-O)(micro
      O(2)CAr(Tol))(2)(Me(3)TACN)(2)](OTf)(2) (2), the only detectable iron-containing
      species during the course of the reaction, can itself promote the reaction.
      Phosphine oxidation is coupled to the catalytic oxidation of THF solvent to
      afford, selectively, the C-C bond-cleavage product 3-hydroxypropylformate, an
      unprecedented transformation. After consumption of the phosphine, solvent
      oxidation continues but results in the products 2-hydroperoxytetrahydrofuran,
      butyrolactone, and butyrolactol. The similarities of the reaction pathways
      observed in the presence and absence of catalyst, as well as (18)O labeling,
      solvent dependence, and radical probe experiments, provide evidence that the
      oxidation is initiated by a metal-centered H-atom abstraction from THF. A
      mechanism for catalysis is proposed that accounts for the coupled oxidation of
      the phosphine and the THF ring-opening reaction.

PMID- 15236557
TI  - A series of trinuclear Cu(II)Ln(III)Cu(II) complexes derived from 2,6
      Di(acetoacetyl)pyridine: synthesis, structure, and magnetism.
AB  - A series of trinuclear Cu(II)Ln(III)Cu(II) complexes with the bridging ligand 2,6
      di(acetoacetyl)pyridine have been prepared by one-pot reaction with
      Cu(NO(3))(2).3H(2)O and Ln(NO(3))(3).nH(2)O in methanol. X-ray crystallographic
      studies for all the complexes indicate that two L(2)(-) ligands selectively
      sandwich two Cu(II) ions with the 1,3-diketonate entities and one Ln(III) ion
      with the 2,6-acetylpyridine entity to form a trinuclear CuLnCu core bridged by
      the enolate oxygen atoms. Cryomagnetic properties of the complexes are studied
      with respect to the electronic structure of the Ln ion.

PMID- 15236558
TI  - Stabilization of calcium- and terbium-carboxylate bonds by NH...O hydrogen bonds
      in a mononuclear complex: a functional model of the active site of calcium
      binding proteins.
AB  - Novel benzoic acid ligands with bulky amide groups at the ortho position, 2,6
      (MeCONH)(2)C(6)H(3)CO(2)H (1) and 2,6-(t-BuCONH)(2)C(6)H(3)CO(2)H (2), and their
      tris- and tetrakis(carboxylate) complexes with Ca(II) and Tb(III) ions,
      (NEt(4))(2)[Ca(II)[O(2)C-2,6-(t-BuCONH)(2)C(6)H(3)](4)] (4), [Tb[O(2)C-2,6-(t
      BuNHCO)(2)C(6)H(3)](3)(H(2)O)(3)]] (5), and (NMe)(4)[Tb[O(2)C-2,6-(t
      BuNHCO)(2)C(6)H(3)](4)(thf)] (6), were synthesized. The formation of the NH...O
      hydrogen bonds between the amide NH and carboxylate for 2, (NEt(4))[2,6-(t
      BuCONH)(2)C(6)H(3)CO(2)] (3), and 4 was determined by (1)H NMR spectroscopy in
      solution and in the solid state (CRAMPS, IR). The ligand exchange reactions were
      attempted between 4 and a large excess of 2,4,6- Me(3)C(6)H(3)CO(2)H in
      chloroform-d solution; however, exchange reaction did not take place, indicating
      that the Ca(II) ions bound strongly to the carboxylate in 4. The Ca(II) ion
      binding properties with the benzoate derivatives were also examined using Tb(III)
      ion as a fluorescence probe. These results indicate that the NH...O hydrogen
      bonding between the amide NH and the oxygen atom of the carboxylate contributes
      to strong Ca(II) binding and prevents the dissociation of the calcium-carboxylate
      bond. The X-ray structural analyses of these complexes revealed that the NH.O
      hydrogen-bonded carboxylate ligands prefer the chelate-type coordination and
      create a mononuclear [Ca(O(2)CR)(4)](2)(-) or [Tb(O(2)CR)(4)](-) core with
      anionic charge, which is known only in the active site of calcium-binding
      proteins.

PMID- 15236559
TI  - Possible role of relativistic effects in the plasticity of the coordination
      geometry of cadmium(II). A voltammetric study of the stability of the complexes
      of cadmium(II) with 12-crown-4,15-crown-5 and 18-crown-6 in aqueous solution and
      the structures of [Cd(benzo-18-crown-6)(NCS)(2)] and [K(18-crown-6)][Cd(SCN)(3)].
AB  - A differential pulse voltammetric study of complexes of Cd(II) and Pb(II) with
      crown ethers is reported. Measured log K(1) values for Cd(II) with 18-crown-6
      (1,4,7,10,13,16-hexaoxacyclooctadecane), 15-crown-5 (1,4,7,10,13
      pentaoxacyclopentadecane), and 12-crown-4 (1,4,7,10-tetraoxacyclododecane) are
      respectively 2.53 (+/-0.06), 1.97 (+/-0.07), and 1.72 (+/-0.08) and for Pb(II)
      with 18-crown-6 is 4.17 (+/-0.03), all at 25 degrees C in 0.1 M LiNO(3). Cd(II)
      is smaller than is usually associated with strong bonding with crown ethers. The
      high log K(1) values for Cd(2+) with crown ethers found here are discussed in
      terms of distortion of Cd(II) by relativistic effects. The resulting plasticity
      of the coordination geometry of the Cd(II) ion allows it to meet the metal ion
      size requirements of all the crown ethers, allowing high log K(1) values to
      occur. Crystal structures for [Cd(bz-18-crown-6)(SCN)(2)] (1) (bz-18-crown-6 =
      benzo-1,4,7,10,13,16-hexaoxacyclooctadecane) and [K(18-crown-6)][Cd(SCN)(3)] (2)
      are reported. 1 was triclinic, space group P1, a = 8.5413(2), b = 10.0389(2), and
      c = 13.4644(2) A, alpha = 94.424(1), beta = 102.286(1), and gamma = 93.236(1)
      degrees, Z = 2, and final R = 0.023. 2 was orthorhombic, space group Cmc2(1), a =
      14.7309(3), b = 15.1647(3), and c = 10.6154(2) A, Z = 4, and final R = 0.020. In
      1, the Cd occupies the cavity of the bz-18-crown-6 with long average Cd-O bond
      lengths of 2.65 A and is N-bonded to the thiocyanates with short average Cd-N
      bonds of 2.12 A. In [Cd(bz-18-crown-6)(SCN)(2)], the linear coordination
      involving the Cd and the two N-bonded thiocyanate groups in 1 is discussed in
      terms of the role of relativistic effects in the tendency to linear coordination
      geometry in group 12 metal ions. In 2 Cd forms a polymeric structure involving
      thiocyanate bridges between Cd atoms and K(+) occupies the cavity of the crown
      ether. 2 highlights the fact that cadmium is almost never S-bonded to thiocyanate
      except in bridging thiocyanates.

PMID- 15236560
TI  - New halide-centered discrete Ag(I)(8) cubic clusters containing diselenophosphate
      ligands, [Ag(8)(X)[Se(2)P(OR)(2)](6)](PF(6)) (X = Cl, Br; R = Et, Pr, (i)Pr):
      syntheses, structures, and DFT calculations.
AB  - Six clusters Ag(8)(micro(8)-X)[Se(2)P(OR)(2)](6)(PF(6)) (R = Et, X = Cl, 1a, X =
      Br, 1b; R = Pr, X = Cl, 2a, X = Br, 2b; R = (i)Pr, X = Cl, 3a, X = Br, 3b) were
      isolated from the reaction of [Ag(CH(3)CN)(4)](PF(6)), NH(4)[Se(2)P(OR)(2)], and
      Bu(4)NX in a molar ratio of 4:3:1 in CH(2)X(2). Positive FAB mass spectra show
      m/z peaks at 2573.2 for 1a, 2617.3 for 1b, 2740.9 for 2a, 2786.9 for 2b, 2742.3
      for 3a, and 2787.0 for 3b due to respective molecular cation, (M - PF(6))(+).
      (31)P NMR spectra of 1a-3b display a singlet at delta 82.3, 81.5, 82.9, 81.7,
      76.3, and 75.8 ppm with a set of satellites (J(PSe) = 661, 664, 652, 652, 656,
      and 656 Hz, respectively). The X-ray structure (1a-2b) consists of a discrete
      cationic cluster in which eight silver ions are linked by six diselenophosphate
      ligands and a central micro(8)-Cl or micro(8)-Br ion with a noncoordinating
      PF(6)(-) anion. The shape of the molecule is a halide-centered distorted Ag(8)
      cubic cluster. The dsep ligand exhibits a tetrametallic tetraconnective
      (micro(2), micro(2)) coordination pattern, and each caps on a square face of the
      cube. Each silver atom of the cube is coordinated by three selenium atoms and the
      central chloride or bromide ion. Additionally, molecular orbital calculations at
      the B3LYP level of the density functional theory have been carried out to study
      the Ag-micro(8)-X (X = Cl, Br) interactions for cluster cations [Ag(8)(micro(8)
      X)[Se(2)P(OR)(2)](6)](+). Calculations show very weak bonding interactions exist
      between micro(8)-X and Ag atoms of the cube.

PMID- 15236561
TI  - Energy transfer pathways in dinuclear heteroleptic polypyridyl complexes: through
      space vs through-bond interaction mechanisms.
AB  - A series of homo- and heteronuclear ruthenium and osmium polypyridyl complexes
      with the bridging ligands 1,3-bis(5-(2-pyridyl)-1H-1,2,4-triazol-3-yl)benzene
      (H(2)mL) and 1,4-bis(5-(2-pyridyl)-1H-1,2,4-triazol-3-yl)benzene (H(2)pL) are
      reported. The photophysical properties of these compounds are investigated, and
      particular attention is paid to the heteronuclear (RuOs) compounds, which exhibit
      dual emission. This is in contrast to phenyl-bridged polypyridine Ru-Os complexes
      with a similar metal-metal distance, in which the Ru emission is strongly
      quenched because the nature of the bridging ligand allows for an efficient
      through-bond coupling. The results obtained for the compounds reported here
      suggest that energy transfer is predominantly taking place via a dipole-dipole,
      Forster type, mechanism, that may dominate when through-bond coupling is weak.
      This is in stark contrast to ground state interaction, which is found to be
      critically dependent on the nature of the bridging unit employed.

PMID- 15236562
TI  - Molecular structures of magnesium dichloride sheets and nanoballs.
AB  - The structures and relative stabilities of (MgCl(2))(n)() sheetlike clusters and
      nanoballs were studied by quantum chemical methods. The sheets as discrete
      molecules were studied up to Mg(100)Cl(200). Their stabilities increase
      systematically as a function of the size of the sheet. Periodic ab initio
      calculations were performed for (001) monolayer sheets of alpha- and beta
      MgCl(2), beta-sheet being slightly favored. Nanoballs were constructed from
      Archimedean polyhedra, producing tetrahedral, octahedral, and icosahedral
      symmetries, and were studied up to Mg(60)Cl(120). Nanoballs prefer to take the
      shape of truncated cuboctahedron (Mg(48)Cl(96)). Comparisons to sheetlike
      clusters and periodic calculations suggest that magnesium dichloride nanoballs
      are stable.

PMID- 15236563
TI  - Photolabile ruthenium nitrosyls with planar dicarboxamide tetradentate N(4)
      ligands: effects of in-plane and axial ligand strength on NO release.
AB  - Four ruthenium nitrosyls, namely [(bpb)Ru(NO)(Cl)] (1), [(Me(2)bpb)Ru(NO)(Cl)]
      (2), [(Me(2)bpb)Ru(NO)(py)](BF(4)) (3), and [(Me(2)bqb)Ru(NO)(Cl)] (4) (H(2)bpb =
      1,2-bis(pyridine-2-carboxamido)benzene, H(2)Me(2)bpb = 1,2-bis(pyridine-2
      carboxamido)-4,5-dimethylbenzene, H(2)Me(2)bqb = 1,2-bis(quinaldine-2
      carboxamido)-4,5-dimethylbenzene; H is the dissociable amide proton), have been
      synthesized and characterized by spectroscopy and X-ray diffraction analysis. All
      four complexes exhibit nu(NO) in the range 1830-1870 cm(-)(1) indicating the [Ru
      NO](6) configuration. Clean (1)H NMR spectra in CD(3)CN (or (CD(3))(2)SO) confirm
      the S = 0 ground state for all four complexes. Although the complexes are
      thermally stable, they release NO upon illumination. Rapid NO dissociation occurs
      when solutions of 1-3 in acetonitrile (MeCN) or DMF are exposed to low-intensity
      (7 mW) UV light (lambda(max) = 302 nm). Electron paramagnetic resonance (EPR)
      spectra of the photolyzed solutions display anisotropic signals at g
      approximately 2.00 that confirm the formation of solvated low-spin Ru(III)
      species upon NO release. The ligand trans to bound NO namely, anionic Cl(-) and
      neutral pyridine, has significant effect on the electronic and NO releasing
      properties of these complexes. Change in the in-plane ligand strength also has
      effects on the rate of NO release. The absorption maximum (lambda(max)) of 4 is
      significantly red shifted (455 nm in DMF) compared to the lambda(max) values of 1
      3 (380-395 nm in DMF) due to the extension of conjugation on the in-plane ligand
      frame. As a consequence, 4 is also sensitive to visible light and release NO
      (albeit at a slower rate) upon illumination to low-intensity visible light
      (lambda > 465 nm). Collectively, the photosensitivity of the present series of
      ruthenium nitrosyls demonstrates that the extent of NO release and their
      wavelength dependence can be modulated by changes of either the in-plane or the
      axial ligand (trans to bound NO) field strength.

PMID- 15236564
TI  - Electrochemistry of metal phthalocyanines in organic solvents at variable
      pressure.
AB  - High-pressure electrochemical investigations of representative
      metallophthalocyanines in solution are reported. The selected systems were ZnPc,
      CoPc, FePc, and CoTNPc (Pc = phthalocyanine, TNPc =
      tetraneopentoxyphthalocyanine) in several donor solvents and (for CoTNPc)
      dichlorobenzene, with [Bu(4)N][ClO(4)] as supporting electrolyte and a
      conventional Pt electrode referred to Ag(+)(CH(3)CN)/Ag. Electrode reaction
      volumes deltaV(cell) for CoTNPc and ZnPc show that consecutive ring reductions
      result in progressive increases in electrostriction of solvent in accordance with
      Drude-Nernst theory. Reductions of the metal center in CoTNPc and CoPc, however,
      result in much less negative values of deltaV(cell) than would be expected by
      analogy with ring reductions of the same charge type. This is attributable to
      loss of axial ligands following the insertion of antibonding 3d(z)2 electrons on
      going from Co(III) to low-spin Co(II) and then Co(I). In the same vein, rate
      constants for reduction of Co(III) centers to Co(II) were an order of magnitude
      slower than those for other metal center or phthalocyanine ring reductions
      because of Franck-Condon restrictions. The volumes of activation deltaV(el) were
      invariably positive for all the electrode reactions and in most cases were
      roughly equal to the volumes of activation for reactant diffusion deltaV(diff)(),
      indicating predominant rate control by solvent dynamics rather than by activation
      in the manner of transition-state theory for which negative deltaV(el) values are
      expected. For CoTNPc and CoPc in donor solvents, the deltaV(cell) and deltaV(el)
      data are consistent with the assignments of the successive reduction steps made
      for CoTNPc in DMF by Nevin et al. (Inorg. Chem. 1987, 26, 570).

PMID- 15236565
TI  - Reduction and oxidation of hydroperoxo rhodium(III) complexes by halides and
      hypobromous acid.
AB  - Oxygen atom transfer from trans-L(H(2)O)RhOOH(2+) [L = [14]aneN(4) (L(1)), meso
      Me(6)[14]aneN(4) (L(2)), and (NH(3))(4)] to iodide takes place according to the
      rate law -d[L(H(2)O)RhOOH(2+)]/dt = k(I)[L(H(2)O)RhOOH(2+)][I(-)][H(+)]. At 0.10
      M ionic strength and 25 degrees C, the rate constant k(I)/M(-)(2) s(-)(1) has
      values of 8.8 x 10(3) [L = (NH(3))(4)], 536 (L(1)), and 530 (L(2)). The final
      products are LRh(H(2)O)(2)(3+) and I(2)/I(3)(-). The
      (NH(3))(4)(H(2)O)RhOOH(2+)/Br(-) reaction also exhibits mixed third-order
      kinetics with k(Br) approximately 1.8 M(-)(2) s(-)(1) at high concentrations of
      acid (close to 1 M) and bromide (close to 0.1 M) and an ionic strength of 1.0 M.
      Under these conditions, Br(2)/Br(3)(-) is produced in stoichiometric amounts. As
      the concentrations of acid and bromide decrease, the reaction begins to generate
      O(2) at the expense of Br(2), until the limit at which [H(+)] <or= 0.10 M and
      [Br(-)] <or= 0.010 M, when Br(2)/Br(3)(-) is no longer observed and O(2) is
      produced quantitatively. At this limit, the loss of (NH(3))(4)(H(2)O)RhOOH(2+) is
      about twice as fast as it is at the high [H(+)] and [Br(-)] extreme, and the
      stoichiometry is 2(NH(3))(4)(H(2)O)RhOOH(2+) --> 2(NH(3))(4)(H(2)O)RhOH(2+) +
      O(2); i.e., the reaction has turned into the bromide-catalyzed disproportionation
      of coordinated hydroperoxide. In the proposed mechanism, the hydrolysis of the
      initially formed Br(2) produces HOBr, the active oxidant for the second
      equivalent of (NH(3))(4)(H(2)O)RhOOH(2+). The rate constant k(HOBr) for the
      HOBr/(NH(3))(4)(H(2)O)RhOOH(2+) reaction is 2.9 x 10(8) M(-)(1) s(-)(1).

PMID- 15236566
TI  - Ruthenium tris(pyrazolyl)borate diazo complexes: preparation of aryldiazenido,
      aryldiazene, and hydrazine derivatives.
AB  - Tris(pyrazolyl)borate aryldiazenido complexes [RuTpLL'(ArN(2))](BF(4))(2) (1-3)
      [Ar = C(6)H(5), 4-CH(3)C(6)H(4); Tp = hydridotris(pyrazolyl)borate; L = P(OEt)(3)
      or PPh(OEt)(2), L' = PPh(3); L = L' = P(OEt)(3)] were prepared by allowing
      dihydrogen [RuTp(eta(2)-H(2))LL'](+) derivatives to react with aryldiazonium
      cations. Spectroscopic characterization (IR, (15)N NMR) using the (15)N-labeled
      derivatives strongly supports the presence of a linear [Ru]-NN-Ar aryldiazenido
      group. Hydrazine complexes [RuTp(RNHNH(2))LL']BPh(4) (4-6) [R = H, CH(3),
      C(6)H(5), 4-NO(2)C(6)H(4); L = P(OEt)(3) or PPh(OEt)(2), L' = PPh(3); L = L' =
      P(OEt)(3)] were also prepared by reacting the [RuTp(eta(2)-H(2))LL'](+) cation
      with an excess of hydrazine. The complexes were characterized spectroscopically
      (IR and NMR) and by X-ray crystal structure determination of the
      [RuTp(CH(3)NHNH(2))[P(OEt)(3)](PPh(3))]BPh(4) (4d) derivative.
      Tris(pyrazolyl)borate aryldiazene complexes [RuTp(ArN=NH)LL']BPh(4) (7-9) (Ar =
      C(6)H(5), 4-CH(3)C(6)H(4)) were prepared following three different methods: (i).
      by allowing hydride species RuHTpLL' to react with aryldiazonium cations in
      CH(2)Cl(2); (ii). by treating aryldiazenido [RuTpLL'(ArN(2))](BF(4))(2) with
      LiBHEt(3) in CH(2)Cl(2); (iii). by oxidizing arylhydrazine
      [RuTp(ArNHNH(2))LL']BPh(4) complexes with Pb(OAc)(4) in CH(2)Cl(2) at -30 degrees
      C. Methyldiazene complexes [RuTp(CH(3)N=NH)LL']BPh(4) were also prepared by the
      oxidation of the corresponding methylhydrazine [RuTp(CH(3)NHNH(2))LL']BPh(4) with
      Pb(OAc)(4).

PMID- 15236567
TI  - Rhenium-to-benzoylpyridine and rhenium-to-bipyridine MLCT excited states of fac
      [Re(Cl)(4-benzoylpyridine)(2)(CO)(3)] and fac-[Re(4
      benzoylpyridine)(CO)(3)(bpy)](+): a time-resolved spectroscopic and
      spectroelectrochemical study.
AB  - The lowest allowed electronic transition of fac-[Re(Cl)(CO)(3)(bopy)(2)] (bopy =
      4-benzoylpyridine) has a Re --> bopy MLCT character, as revealed by UV-vis and
      stationary resonance Raman spectroscopy. Accordingly, the lowest-lying, long
      lived, excited state is Re --> bopy (3)MLCT. Electronic depopulation of the
      Re(CO)(3) unit and population of a bopy pi orbital upon excitation are evident by
      the upward shift of nu(CO) vibrations and a downward shift of the ketone nu(C=O)
      vibration, respectively, seen in picosecond time-resolved IR spectra. Moreover,
      reduction of a single bopy ligand in the (3)MLCT excited state is indicated by
      time-resolved visible and resonance Raman (TR(3)) spectra that show features
      typical of bopy(*)(-). In contrast, the lowest allowed electronic transition and
      lowest-lying excited state of a new complex fac-[Re(bopy)(CO)(3)(bpy)](+) (bpy =
      2,2'-bipyridine) have been identified as Re --> bpy MLCT with no involvement of
      the bopy ligand, despite the fact that the first reduction of this complex is
      bopy-localized, as was proven spectroelectrochemically. This is a rare case in
      which the localizations of the lowest MLCT excitation and the first reduction are
      different. (3)MLCT excited states of both fac-[Re(Cl)(CO)(3)(bopy)(2)] and fac
      [Re(bopy)(CO)(3)(bpy)](+) are initially formed vibrationally hot. Their
      relaxation is manifested by picosecond dynamic shifts of nu(C(triple bond)O) IR
      bands. The X-ray structure of fac-[Re(bopy)(CO)(3)(bpy)]PF(6).CH(3)CN has been
      determined.

PMID- 15236568
TI  - Redox functions of carotenoids in photosynthesis.
AB  - Carotenoids are well-known as light-harvesting pigments. They also play important
      roles in protecting the photosynthetic apparatus from damaging reactions of
      chlorophyll triplet states and singlet oxygen in both plant and bacterial
      photosynthesis. Recently, it has been found that beta-carotene functions as a
      redox intermediate in the secondary pathways of electron transfer within
      photosystem II and that carotenoid cation radicals are transiently formed after
      photoexcitation of bacterial light-harvesting complexes. The redox role of beta
      carotene in photosystem II is unique among photosynthetic reaction centers and
      stems from the very strongly oxidizing intermediates that form in the process of
      water oxidation. Because of the extended pi-electron-conjugated system of
      carotenoid molecules, the cation radical is delocalized. This enables beta
      carotene to function as a "molecular wire", whereby the centrally located
      oxidizing species is shuttled to peripheral redox centers of photosystem II where
      it can be dissipated without damaging the system. The physiological significance
      of carotenoid cation radical formation in bacterial light-harvesting complexes is
      not yet clear, but may provide a novel mechanism for excitation energy
      dissipation as a means of photoprotection. In this paper, the redox reactions of
      carotenoids in photosystem II and bacterial light-harvesting complexes are
      presented and the possible roles of carotenoid cation radicals in photoprotection
      are discussed.

PMID- 15236569
TI  - Heme A synthase does not incorporate molecular oxygen into the formyl group of
      heme A.
AB  - Heme A is an obligatory cofactor in all eukaryotic and many prokaryotic
      cytochrome c oxidases. The final step in heme A biosynthesis requires the
      oxidation of the C8 methyl substituent on pyrrole ring D to an aldehyde, a
      reaction catalyzed by heme A synthase. To effect this transformation, heme A
      synthase is proposed to utilize a heme B cofactor, oxidizing the substrate via
      successive monooxygenase reactions. Consistent with this hypothesis, the activity
      of heme A synthase is found to be strictly dependent on molecular oxygen.
      Surprisingly, when cells expressing heme A synthase were incubated with (18)O(2),
      no significant incorporation of label was observed in heme A, the C8 alcohol
      intermediate, or the C8 overoxidized byproduct. Conversely, when the cells were
      grown in H(2)(18)O, partial labeling was observed at every heme oxygen position.
      These results suggest that the oxygen on the heme A aldehyde is derived from
      water. Although our data do not allow us to exclude the possibility of exchange
      with water inside of the cell, the results seem to question a mechanism utilizing
      successive monooxygenase reactions and support instead a mechanism of heme O
      oxidation via electron transfer.

PMID- 15236571
TI  - Structure of the plasminogen kringle 4 binding calcium-free form of the C-type
      lectin-like domain of tetranectin.
AB  - Tetranectin is a homotrimeric protein containing a C-type lectin-like domain.
      This domain (TN3) can bind calcium, but in the absence of calcium, the domain
      binds a number of kringle-type protein ligands. Two of the calcium-coordinating
      residues are also critical for binding plasminogen kringle 4 (K4). The structure
      of the calcium free-form of TN3 (apoTN3) has been determined by NMR. Compared to
      the structure of the calcium-bound form of TN3 (holoTN3), the core region of
      secondary structural elements is conserved, while large displacements occur in
      the loops involved in calcium or K4 binding. A conserved proline, which was found
      to be in the cis conformation in holoTN3, is in apoTN3 predominantly in the trans
      conformation. Backbone dynamics indicate that, in apoTN3 especially, two of the
      three calcium-binding loops and two of the three K4-binding residues exhibit
      increased flexibility, whereas no such flexibility is observed in holoTN3. In the
      20 best nuclear magnetic resonance structures of apoTN3, the residues critical
      for K4 binding span a large conformational space. Together with the relaxation
      data, this indicates that the K4-ligand-binding site in apoTN3 is not preformed.

PMID- 15236570
TI  - KappaM-conotoxin RIIIK, structural and functional novelty in a K+ channel
      antagonist.
AB  - Venomous organisms have evolved a variety of structurally diverse peptide
      neurotoxins that target ion channels. Despite the lack of any obvious structural
      homology, unrelated toxins that interact with voltage-activated K(+) channels
      share a dyad motif composed of a lysine and a hydrophobic amino acid residue,
      usually a phenylalanine or a tyrosine. kappaM-Conotoxin RIIIK (kappaM-RIIIK),
      recently characterized from the cone snail Conus radiatus, blocks Shaker and
      TSha1 K(+) channels. The functional and structural study presented here reveals
      that kappaM-conotoxin RIIIK blocks voltage-activated K(+) channels with a novel
      pharmacophore that does not comprise a dyad motif. Despite the quite different
      amino acid sequence and no overlap in the pharmacological activity, we found that
      the NMR solution structure of kappaM-RIIIK in the C-terminal half is highly
      similar to that of mu-conotoxin GIIIA, a specific blocker of the skeletal muscle
      Na(+) channel Na(v)1.4. Alanine substitutions of all non-cysteine residues
      indicated that four amino acids of kappaM-RIIIK (Leu1, Arg10, Lys18, and Arg19)
      are key determinants for interaction with K(+) channels. Following the hypothesis
      that Leu1, the major hydrophobic amino acid determinant for binding, serves as
      the hydrophobic partner of a dyad motif, we investigated the effect of several
      mutations of Leu1 on the biological function of kappaM-RIIIK. Surprisingly, both
      the structural and mutational analysis suggested that, uniquely among well
      characterized K(+) channel-targeted toxins, kappaM-RIIIK blocks voltage-gated
      K(+) channels with a pharmacophore that is not organized around a lysine
      hydrophobic amino acid dyad motif.

PMID- 15236572
TI  - Crystal structure of the ascorbate peroxidase-salicylhydroxamic acid complex.
AB  - Ascorbate peroxidase is a bifunctional peroxidase that catalyzes the H(2)O(2)
      dependent oxidation of both ascorbate and various aromatic substrates. The
      ascorbate binding site was recently identified as being close to the gamma-heme
      edge [Sharp, K. H., Mewies, M., Moody, P. C. E., and Raven, E. L. (2003)Nat.
      Struct. Biol. 10, 303-307]. In this work, the X-ray crystal structure of
      recombinant soybean cytosolic ascorbate peroxidase (rsAPX) in complex with
      salicylhydroxamic acid (SHA) has been determined to 1.46 A. The SHA molecule is
      bound close to the delta-heme edge in a cavity that connects the distal side of
      the heme to the surface of the protein. There are hydrogen bonds between the
      phenolic hydroxide of the SHA and the main chain carbonyl of Pro132, between the
      carbonyl oxygen of SHA and the side chain guanadinium group of Arg38, and between
      the hydroxamic acid group and the indole nitrogen of Trp41. The structure
      provides the first information about the location of the aromatic binding site in
      ascorbate peroxidase and, together with our previous data [Sharp, K. H., et al.
      (2003) Nat. Struct. Biol. 10, 303-307], completes the structural description of
      the binding properties of ascorbate peroxidase. The mechanistic implications of
      the results are discussed in terms of our current understanding of how APX
      catalyzes oxidation of different types of substrates bound at different
      locations.

PMID- 15236573
TI  - Electron transfer in acetohydroxy acid synthase as a side reaction of catalysis.
      Implications for the reactivity and partitioning of the carbanion/enamine form of
      (alpha-hydroxyethyl)thiamin diphosphate in a "nonredox" flavoenzyme.
AB  - Acetohydroxy acid synthases (AHAS) are thiamin diphosphate- (ThDP-) and FAD
      dependent enzymes that catalyze the first common step of branched-chain amino
      acid biosynthesis in plants, bacteria, and fungi. Although the flavin cofactor is
      not chemically involved in the physiological reaction of AHAS, it has been shown
      to be essential for the structural integrity and activity of the enzyme. Here, we
      report that the enzyme-bound FAD in AHAS is reduced in the course of catalysis in
      a side reaction. The reduction of the enzyme-bound flavin during turnover of
      different substrates under aerobic and anaerobic conditions was characterized by
      stopped-flow kinetics using the intrinsic FAD absorbance. Reduction of enzyme
      bound FAD proceeds with a net rate constant of k' = 0.2 s(-1) in the presence of
      oxygen and approximately 1 s(-1) under anaerobic conditions. No transient flavin
      radicals are detectable during the reduction process while time-resolved
      absorbance spectra are recorded. Reconstitution of the binary enzyme-FAD complex
      with the chemically synthesized intermediate 2-(hydroxyethyl)-ThDP also results
      in a reduction of the flavin. These data provide evidence for the first time that
      the key catalytic intermediate 2-(hydroxyethyl)-ThDP in the carbanionic/enamine
      form is not only subject to covalent addition of 2-keto acids and an oxygenase
      side reaction but also transfers electrons to the adjacent FAD in an
      intramolecular redox reaction yielding 2-acetyl-ThDP and reduced FAD. The
      detection of the electron transfer supports the idea of a common ancestor of
      acetohydroxy acid synthase and pyruvate oxidase, a homologous ThDP- and FAD
      dependent enzyme that, in contrast to AHASs, catalyzes a reaction that relies on
      intercofactor electron transfer.

PMID- 15236574
TI  - Detailed kinetic studies of an aggregating inhibitor; inhibition of
      phosphomannomutase/phosphoglucomutase by disperse blue 56.
AB  - Phosphomannomutase/phosphoglucomutase occupies a central position in the pathways
      by which several virulence factors are synthesized in Pseudomonas aeruginosa.
      Virtual screening was used to identify potential inhibitors of
      phosphomannomutase/ phosphoglucomutase, and one compound, the anthraquinone-based
      dye Disperse Blue 56, showed potent inhibition in vitro. The kinetics of
      inhibition was complex; the time courses for reactions in the presence of the
      inhibitor were biphasic, suggestive of slow-binding inhibition. Quantitative
      analysis of the progress curves and preincubation experiments demonstrated that
      slow-binding inhibition was not occurring, however. Initial velocity kinetic
      studies indicated that Disperse Blue 56 was a parabolic, noncompetitve inhibitor.
      Progress curves for reactions in the presence of Disperse Blue 56 could be fitted
      very well by a model in which 2 equiv of the inhibitor bound to free enzyme or
      the enzyme-substrate complex. The inhibition was largely relieved by the
      inclusion of 0.01% Triton X-100 in the assay solutions, which has been suggested
      to be the hallmark for inhibition by compounds that exert their effect through
      aggregates [McGovern, S. L., Caselli, E., Grigorieff, N., and Shiochet, B. K.
      (2002) J. Med. Chem. 45, 1712-1722]. Our kinetic data appear to be consistent
      with either inhibition by a dimer of Disperse Blue 56 or inhibition by a Disperse
      Blue 56 aggregate, but the latter appears much more likely. We present a detailed
      analysis of the system to provide further information that may help in the
      recognition of inhibition through aggregation.

PMID- 15236575
TI  - Crystal structure of 4-chlorobenzoate:CoA ligase/synthetase in the unliganded and
      aryl substrate-bound states.
AB  - 4-Chlorobenzoate:CoA ligase (CBAL) is a member of a family of adenylate-forming
      enzymes that catalyze two-step adenylation and thioester-forming reactions. In
      previous studies, we have provided structural evidence that members of this
      enzyme family (exemplified by acetyl-CoA synthetase) use a large domain rotation
      to catalyze the respective partial reactions [A. M. Gulick, V. J. Starai, A. R.
      Horswill, K. M. Homick, and J. C. Escalante-Semerena, (2003) Biochemistry 42,
      2866-2873]. CBAL catalyzes the synthesis of 4-chlorobenzoyl-CoA, the first step
      in the 4-chlorobenzoate degredation pathway in PCB-degrading bacteria. We have
      solved the 2.0 A crystal structure of the CBAL enzyme from Alcaligenes sp. AL3007
      using multiwavelength anomalous dispersion. The results demonstrate that in the
      absence of any ligands, or bound to the aryl substrate 4-chlorobenzoate, the
      enzyme adopts the conformation poised for catalysis of the adenylate-forming half
      reaction. We hypothesize that coenzyme A binding is required for stabilization of
      the alternate conformation, which catalyzes the 4-CBA-CoA thioester-forming
      reaction. We have also determined the structure of the enzyme bound to the aryl
      substrate 4-chlorobenzoate. The aryl binding pocket is composed of Phe184,
      His207, Val208, Val209, Phe249, Ala280, Ile303, Gly305, Met310, and Asn311. The
      structure of the 4-chlorobenzoate binding site is discussed in the context of the
      binding sites of other family members to gain insight into substrate specificity
      and evolution of new function.

PMID- 15236576
TI  - The active site cysteine of arginine kinase: structural and functional analysis
      of partially active mutants.
AB  - Arginine kinase buffers cellular ATP levels by catalyzing reversible phosphoryl
      transfer between ATP and arginine. A conserved cysteine has long been thought
      important in catalysis. Here, cysteine 271 of horseshoe crab arginine kinase has
      been mutated to serine, alanine, asparagine, or aspartate. Catalytic turnover
      rates were 0.02-1.0% of wild type, but the activity of uncharged mutations could
      be partially rescued with chloride. Steady-state binding constants were slightly
      increased, more so for phospho-L-arginine than ADP. Substrate binding synergy
      observed in many phosphagen kinases was reduced or eliminated in mutant enzymes.
      The crystallographic structure of the alanine mutant at 2.3 A resolution,
      determined as a transition state analogue complex with arginine, nitrate, and
      MgADP, was nearly identical to wild type. Enzyme-substrate interactions are
      maintained as in wild type, and substrates remain at least roughly aligned for in
      line phosphoryl transfer. Homology models with serine, asparagine, or aspartate
      replacing the active site cysteine similarly show only minor structural changes.
      Most striking, however, is the presence in the C271A mutant crystallographic
      structure of a chloride ion within 3.5 A of the nonreactive N(eta) substrate
      nitrogen, approximating the position of the sulfur in the wild-type's cysteine.
      Together, the results contradict prevailing speculation that the cysteine
      mediates a substrate-induced conformational change, confirm that it is the
      thiolate form that is relevant to catalysis, and suggest that one of its roles is
      to help to enhance the catalytic rate through electrostatic stabilization of the
      transition state.

PMID- 15236577
TI  - Oligodeoxynucleotides having a loop consisting of 3'-deoxy-4'-C-(2
      hydroxyethyl)thymidines form stable hairpins.
AB  - Components that form stable hairpin loops are highly useful for the development
      of functional DNA and RNA molecules. We have designed and synthesized a sugar
      modified thymidine analogue, 3'-deoxy-4'-C-(2-hydroxyethyl)thymidine (X), as a
      nucleosidic loop component stabilizing the hairpin structure. The ODNs I-1-4, 5'
      d[CGAACG-X(n)-CGTTCG]-3' (I-1, n = 1; I-2, n = 2; I-3, n = 3; I-4, n = 4),
      forming the hairpin loop structures, of which the loop moiety consisted of the
      analogue X, and also the corresponding unmodified ODNs II-1-4, 5'-d[CGAACG-T(n)
      CGTTCG]-3' (II-1, n = 1; II-2, n = 2;II-3, n = 3; II-4, n = 4), having a
      thymidine loop, were synthesized by the phosphoramidite method. The melting
      temperatures (T(m)) of the ODNs I-1-4 containing X in the loop moiety at 5 microM
      were 67.1, 68.1, 73.0, and 69.3 degrees C, respectively, and those of the control
      natural ODNs II-1-4 were 65.3, 67.0, 69.2, and 68.8 degrees C, respectively.
      Thus, the ODNs I-1-4 formed a more thermally stable hairpin than the
      corresponding unmodified ODNs II-1-4 having an equal number of loop residues. The
      hairpin structures of the modified ODNs I-1-4 and the unmodified ODNs II-1-4 were
      investigated by CD spectroscopy and molecular mechanics calculations. These
      results showed that the 4'-branched nucleoside X can stabilize hairpin structures
      when it is present in the loop moiety, probably due to the flexibility of the one
      carbon-elongated 4'-branched structure.

PMID- 15236578
TI  - Refinement of a homology model of the mu-opioid receptor using distance
      constraints from intrinsic and engineered zinc-binding sites.
AB  - Publication of the rhodopsin X-ray structure has facilitated the development of
      homology models of other G protein-coupled receptors. However, possible shifts of
      transmembrane (TM) alpha helices, expected variations in helical distortions, and
      differences in loop size necessitate experimental verification of these
      comparative models. To refine a rhodopsin-based homology model of the mu-opioid
      receptor (MOR), we experimentally determined structural-distance constraints from
      intrinsic and engineered metal-binding sites in the rat MOR. Investigating the
      relatively high intrinsic affinity of MOR for Zn(2+) (IC(50) approximately
      30microM), we observed that mutation of His(319) (TM7) abolished Zn(2+)
      inhibition of ligand binding, while mutation of Asp(216) (extracellular loop 2)
      decreased the effect of Zn(2+), suggesting these residues participate in the
      intrinsic Zn(2+)-binding center of MOR. To verify the relative orientation of TM5
      and TM6 and to examine whether a rhodopsin-like alpha aneurism is present in TM5,
      we engineered Zn(2+)-binding centers by mutating residues of TM5 and TM6 to Cys
      or His, making use of the native His(297) in TM6 as an additional Zn(2+)
      coordination site. Inhibition of opioid ligand binding by Zn(2+) suggests that
      residues Ile(234) and Phe(237) in TM5 face the binding-site crevice and form a
      metal-binding center with His(297) and Val(300) in TM6. This observation is
      inconsistent with a rhodopsin-like structure, which would locate Ile(234) on the
      lipid-exposed side of TM5, too distant from other residues making up the Zn(2+)
      binding site. Subsequent distance geometry refinement of the MOR model indicates
      that the rhodopsin-like alpha aneurism is likely absent in TM2 but present in
      TM5.

PMID- 15236579
TI  - Crystal structures of unliganded and half-liganded human hemoglobin derivatives
      cross-linked between Lys 82beta1 and Lys 82beta2.
AB  - A number of ligand binding studies of human adult hemoglobin (HbA) cross-linked
      between Lys 82beta(1) and Lys 82beta(2) with bis(3,5-dibromosalicyl)fumarate have
      been reported. The oxygen binding properties of native HbA, including the
      cooperativity and Bohr effect, are not substantially changed by the modification,
      provided care is taken to remove electrophoretically silent impurities arising
      from side reactions. We have refined the high-resolution structure of this
      modified Hb and found it adopts the T state when crystallized in the absence of
      heme ligands, contrary to a previously published structure. These results suggest
      the slightly altered crystal form determined previously may be due to unremoved
      side products of the cross-linking reaction with high oxygen affinity. Two nickel
      substituted Hbs cross-linked in the same way have also been crystallized in the
      presence of carbon monoxide, which binds only to the ferrous heme. In the case of
      the nickel-substituted alpha subunit, the absence of a covalent link between the
      central metal of the heme and the proximal histidine leads to a new conformation
      of the histidine stabilized by a water molecule. This structure may mimic that of
      partially NO-liganded species of HbA; however, overall, the changes are highly
      localized, and both doubly ligated species are in the T conformation.

PMID- 15236580
TI  - Structural details on the binding of antihypertensive drugs captopril and
      enalaprilat to human testicular angiotensin I-converting enzyme.
AB  - Angiotensin converting enzyme (ACE) plays a critical role in the circulating or
      endocrine renin-angiotensin system (RAS) as well as the local regulation that
      exists in tissues such as the myocardium and skeletal muscle. Here we report the
      high-resolution crystal structures of testis ACE (tACE) in complex with the first
      successfully designed ACE inhibitor captopril and enalaprilat, the Phe-Ala-Pro
      analogue. We have compared these structures with the recently reported structure
      of a tACE-lisinopril complex [Natesh et al. (2003) Nature 421, 551-554]. The
      analyses reveal that all three inhibitors make direct interactions with the
      catalytic Zn(2+) ion at the active site of the enzyme: the thiol group of
      captopril and the carboxylate group of enalaprilat and lisinopril. Subtle
      differences are also observed at other regions of the binding pocket. These are
      compared with N-domain models and discussed with reference to published
      biochemical data. The chloride coordination geometries of the three structures
      are discussed and compared with other ACE analogues. It is anticipated that the
      molecular details provided by these structures will be used to improve the
      binding and/or the design of new, more potent domain-specific inhibitors of ACE
      that could serve as new generation antihypertensive drugs.

PMID- 15236581
TI  - The LEF-1 high-mobility group domain undergoes a disorder-to-order transition
      upon formation of a complex with cognate DNA.
AB  - Lymphoid enhancer-binding factor-1 (LEF-1), a member of the high-mobility group
      (HMG) family of proteins, functions as an architectural transcription factor. In
      complex with its cognate DNA, the LEF-1 domain is highly ordered, and its NMR
      spectra are characteristic of a folded globular protein. In contrast, the
      uncomplexed protein exhibits NMR evidence of substantial conformational
      heterogeneity, although circular dichroism spectra indicate that much of the
      alpha-helical secondary structure of the DNA-bound state is retained in the free
      protein. Heteronuclear NMR experiments performed on the free LEF-1 domain reveal
      that helix II and helix III of the HMG domain are folded, although helix III is
      truncated at its C-terminal end relative to the DNA-bound protein. The major
      hydrophobic core between helices II and III appears to be formed, but the minor
      core near the C-terminus of helix III is unstructured in the free protein.
      Backbone resonances of helix I are undetectable, probably as a result of exchange
      broadening due to fluctuations between two or more conformations on a microsecond
      to-millisecond time scale. On the basis of the circular dichroism spectrum, this
      region of the polypeptide appears to adopt helical structure but the helix is not
      fully stabilized in the absence of DNA. These findings argue that, prior to
      binding, bending, and distorting DNA, the HMG domain of LEF-1 exists in a
      segmentally disordered or partially folded state. Upon complex formation, the
      protein domain undergoes a cooperative folding transition with DNA to a highly
      ordered and well-folded state.

PMID- 15236582
TI  - HIV-1 integrase complexes with DNA dissociate in the presence of short
      oligonucleotides conjugated to acridine.
AB  - The human immunodeficiency virus type 1 (HIV-1) integrase is an essential enzyme
      in the life cycle of the virus and is therefore an attractive target for the
      development of new antiviral drugs. Among them, inhibitors which are capable of
      targeting the preassembled integrase/DNA complex are of particular interest,
      because they could suppress integrase activity in the context of the HIV-1
      preintegration complex. Here, we study the mechanism of action of 11-mer
      oligonucleotides, which are efficient inhibitors of the catalytic activity of
      integrase, provided that they are conjugated to a hydrophobic compound, acridine.
      To understand the mechanism of the conjugate inhibitory action, we used a steady
      state fluorescence anisotropy assay, which allowed us to study the stability of
      the integrase/DNA complex in various conditions. We found that oligonucleotide
      acridine conjugates induced the efficient dissociation of preassembled
      integrase/DNA complexes. The simultaneous presence of both acridine and an
      oligonucleotidic moiety is required for the inhibitory activity of conjugates.
      However, the dissociation effect is not dependent on the oligonucleotide
      sequence. Finally, our results suggest that the conjugates bind directly to
      integrase within its complex with DNA at a site different from the viral DNA
      binding site.

PMID- 15236583
TI  - Structural stability and dynamics of hydrogenated and perdeuterated cytochrome
      P450cam (CYP101).
AB  - Perdeuterated and hydrogenated cytochrome P450cam (P450cam), from Pseudomonas
      putida, has been characterized concerning thermal stability and structural
      dynamics. For the first time, Fourier transform infrared (FTIR) spectroscopy was
      used to characterize a perdeuterated protein. The secondary structure
      compositions were determined from the fitted amide I' spectral region, giving
      band populations at 10 degrees C for the perdeuterated protein of 22% between
      1605 and 1624 cm(-1) (beta-sheets), 47% between 1633 and 1650 cm(-1) (alpha-helix
      (29%) plus unordered/3(10)-helix (18%)), and 28% between 1657 and 1677 cm(-1)
      (turns) and for the hydrogenated protein of 22% between 1610 and 1635 cm(-1)
      (beta-sheets), 52% between 1640 and 1658 cm(-1) (alpha-helix (41%) plus
      unordered/3(10)-helix (11%)), and 24% between 1665 and 1680 cm(-1) (turns).
      Thermal unfolding experiments revealed that perdeuterated P450cam was less stable
      than the hydrogenated protein. The midpoint transition temperatures were 60.8 and
      64.4 degrees C for the perdeuterated and hydrogenated P450cam, respectively. Step
      scan time-resolved FTIR was applied to the P450cam-CO complex to study the ligand
      rebinding process after flash photolysis. Rebinding of the ligand occurred with
      the same kinetics and rate constants k(on), 8.9 x 10(4) and 8.3 x 10(4) M(-1) s(
      1) for the perdeuterated and hydrogenated P450cam, respectively.Perdeuterated
      P450cam was expressed for a neutron crystallographic study to determine the
      specific hydration states and hydrogen-bonding networks at the active site. The
      analyses presented here show that perdeuterated P450cam is structurally similar
      to its hydrogenated counterpart, despite its reduced thermal stability,
      suggesting that information obtained from the neutron structure will be
      representative of the normal hydrogenated P450cam.

PMID- 15236584
TI  - Direct detection of phospholamban and sarcoplasmic reticulum Ca-ATPase
      interaction in membranes using fluorescence resonance energy transfer.
AB  - We used fluorescence resonance energy transfer (FRET) to detect and quantitate
      the interaction of the sarcoplasmic reticulum Ca-ATPase (SERCA) with
      phospholamban (PLB) in membranes. PLB inhibits SERCA only at submicromolar Ca. It
      has been proposed that relief of inhibition at micromolar Ca is due to
      dissociation of the inhibitory complex. To test this hypothesis, we co
      reconstituted donor-labeled SERCA and acceptor-labeled I40A-PLB (superinhibitory,
      monomeric PLB mutant) in membranes of defined lipid and protein composition, with
      full retention of Ca-dependent ATPase activity and inhibitory regulation by PLB.
      FRET from SERCA to PLB was measured as a function of membrane concentrations of
      PLB and SERCA, and functional activity was measured on the same samples. The data
      revealed clearly that the stoichiometry of binding is one PLB per SERCA, and that
      binding is a strict function of the ratio of total PLB to SERCA in the membrane.
      We conclude that the dissociation constant of PLB binding to SERCA is far less
      than physiological PLB membrane concentrations. Binding at low Ca (pCa 6.5),
      where I40A-PLB inhibits SERCA, was virtually identical to that at high Ca (pCa
      5.0), where no inhibition was observed. However, the limiting energy transfer at
      saturating PLB was less at high Ca, indicating a greater donor-acceptor distance.
      We conclude that (a) the affinity of PLB for SERCA is so great that PLB is
      essentially a SERCA subunit under physiological conditions and (b) relief of
      inhibition at micromolar Ca is due to a structural rearrangement within the SERCA
      PLB complex, rather than dissociation.

PMID- 15236585
TI  - Phosphorylation and binding interactions of CheY studied by use of Badan-labeled
      protein.
AB  - In the chemotaxis signal transduction pathway of Escherichia coli, the response
      regulator protein CheY is phosphorylated by the receptor-coupled protein kinase
      CheA. Previous studies of CheY phosphorylation and CheY interactions with other
      proteins in the chemotaxis pathway have exploited the fluorescence properties of
      Trp(58), located immediately adjacent to the phosphorylation site of CheY
      (Asp(57)). Such studies can be complicated by the intrinsic fluorescence and
      absorbance properties of CheA and other proteins of interest. To circumvent these
      difficulties, we generated a derivative of CheY carrying a covalently attached
      fluorescent label that serves as a sensitive reporter of phosphorylation and
      binding events and that absorbs and emits light at wavelengths well removed from
      potential interference by other proteins. This labeled version of CheY has the
      (dimethylamino)naphthalene fluorophore from Badan [6-bromoacetyl-2
      (dimethylamino)naphthalene] attached to the thiol group of a cysteine introduced
      at position 17 of CheY by site-directed mutagenesis. Under phosphorylating
      conditions (or in the presence of beryllofluoride), the fluorescence emission of
      Badan-labeled CheY(M17C) exhibited an approximately 10 nm blue shift and an
      approximately 30% increase in signal intensity at 490 nm. The fluorescence of
      Badan-labeled CheY(M17C) also served as a sensitive reporter of CheY-CheA binding
      interactions, exhibiting an approximately 50% increase in emission intensity in
      the presence of saturating levels of CheA. Compared to wild-type CheY, Badan
      labeled CheY exhibited reduced ability to autodephosphorylate and could not
      interact productively with the phosphatase CheZ. However, with respect to
      autophosphorylation and interactions with CheA, Badan-CheY performed identically
      to wild-type CheY, allowing us to explore CheA-CheY phosphotransfer kinetics and
      binding kinetics without interference from the fluorescence/absorbance properties
      of CheA and ATP. These results provide insights into CheY interactions with CheA,
      CheZ, and other components of the chemotaxis signaling pathway.

PMID- 15236586
TI  - Stabilization of an intermediate activation state for transducin by a fluorescent
      GTP analogue.
AB  - The GTP-binding protein (G protein), transducin, serves as a key molecular switch
      in vertebrate vision through the tight regulation of its GTP-binding
      (activation)/GTP hydrolytic (deactivation) cycle by the photoreceptor rhodopsin.
      To better understand the structure-function characteristics of transducin
      activation, we have set out to identify spectroscopic probes that bind to the
      guanine nucleotide-binding site of this G protein and maintain its ability to
      interact with its specific cellular target/effector, the cyclic GMP
      phosphodiesterase (PDE). In this study, we describe the characterization of a
      fluorescently labeled GTP analogue, BODIPY-FL GTPgammaS (BOD-GTPgammaS), that
      binds to the alpha subunit of transducin (alpha(T)) in a rhodopsin- and
      Gbetagamma-dependent manner, similar to the binding of GTP or GTPgammaS, with an
      apparent dissociation constant of 100 nM. The rhodopsin-dependent binding of BOD
      GTPgammaS to alpha(T) is slow, relative to the rate of binding of GTPgammaS,
      particularly under conditions where rhodopsin must act catalytically to stimulate
      the exchange of BOD-GTPgammaS for GDP on multiple alpha(T) subunits. This
      reflects a slower rate of dissociation of rhodopsin and Gbetagamma from alpha(T)
      BOD-GTPgammaS complexes, relative to their rates of dissociation from alpha(T)
      GTPgammaS. The binding of BOD-GTPgammaS occurs without a change in the intrinsic
      tryptophan fluorescence of alpha(T), indicating that only a subtle movement of
      the Switch 2 domain on alpha(T) accompanies the binding of this GTPgammaS
      analogue. Nevertheless, the BOD-GTPgammaS-bound alpha(T) subunit is able to bind
      with high affinity to the recombinant, purified gamma subunit of PDE (gamma(PDE))
      labeled with 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid
      (IAEDANS (K(d) approximately 13 nM)), as well as bind to and stimulate the
      activity of PDE, albeit less efficiently compared to alpha(T)-GTPgammaS. Taken
      together, these findings suggest that the binding of BOD-GTPgammaS to transducin
      causes it to adopt a distinct conformation that appears to be intermediate
      between the inactive and fully active states of alpha(T), and this fluorescent
      nucleotide analogue can be used as a reporter group to characterize the
      interactions of alpha(T) in this conformational state with its biological
      target/effector.

PMID- 15236587
TI  - Transmembrane reorientation of the substrate-binding site in vesicular
      acetylcholine transporter.
AB  - Active transport of acetylcholine (ACh) by vesicular ACh transporter (VAChT) is
      driven by a proton-motive force established by V-ATPase. A published microscopic
      kinetics model predicts the ACh-binding site is primarily oriented toward the
      outside for nontransporting VAChT and toward the inside for transporting VAChT.
      The allosteric ligand [(3)H]vesamicol cannot bind when the ACh-binding site is
      outwardly oriented and occupied by ACh, but it can bind when the ACh site is
      inwardly oriented. The kinetics model was tested in the paper reported here using
      rat VAChT expressed in PC12(A1237) cells. Equilibrium titrations of
      [(3)H]vesamicol binding and ACh competition show that ATP blocks competition
      between vesamicol and ACh in over one-half of the VAChT. NaCl did not mimic ACh
      chloride, and bafilomycin A(1) and FCCP completely blocked the ATP effect, which
      shows that it is mediated by a proton-motive force. The data are consistent with
      reorientation of over one-half of the ACh-binding sites from the outside to the
      inside of vesicles upon activation of transport. The observations support the
      proposed microscopic kinetics model, and they should be useful in characterizing
      effects of mutations on the VAChT transport cycle.

PMID- 15236588
TI  - Position and ionization state of Asp in the core of membrane-inserted alpha
      helices control both the equilibrium between transmembrane and nontransmembrane
      helix topography and transmembrane helix positioning.
AB  - The behavior of model-membrane-inserted polyLeu-rich peptides containing Asp
      residues located at various positions in their hydrophobic core was investigated.
      The topography of the bilayer-inserted alpha helices formed by these peptides was
      evaluated by measuring the emission lambda(max) and quenching the fluorescence of
      a Trp at the center of the peptide sequence. When Asp residues were protonated
      (at low pH), peptides that were incorporated into vesicles composed of
      dioleoylphosphatidylcholine (DOPC) adopted a topography in which the polyLeu
      sequence predominantly formed a normal transmembrane (TM) helix. When Asp
      residues were ionized (at neutral or high pH), topography was altered in a manner
      that would allow the charged Asp residues to reside near the bilayer surface. In
      DOPC vesicles, most peptides repositioned so that the longest segment of
      consecutive hydrophobic residues (12 residue minimum) formed a truncated/shifted
      TM structure. However, peptides with one or two charged Asp residues close to the
      center of the hydrophobic sequence and thus lacking even a 12-residue continuous
      hydrophobic segment, formed a helical non-TM state locating near the bilayer
      surface. At low pH, incorporation of the peptides into thicker bilayers composed
      of dierucoylphosphatidylcholine (DEuPC) resulted in the formation of a mixture of
      the normal TM state and the non-TM helical state located near the bilayer
      surface. In DEuPC vesicles at high pH, the non-TM state tended to predominate.
      How Asp-ionization-dependent shifts in helix topography may regulate the function
      of membrane proteins exposed to environments with differing pH in vivo (e.g.,
      endosomes) is discussed.

PMID- 15236589
TI  - Probing the transition-state structure of dual-specificity protein phosphatases
      using a physiological substrate mimic.
AB  - Dual-specificity phosphatases (DSPs) belong to the large family of protein
      tyrosine phosphatases that contain the active-site motif (H/V)CxxGxxR(S/T), but
      unlike the tyrosine-specific enzymes, DSPs are able to catalyze the efficient
      hydrolysis of both phosphotyrosine and phosphoserine/threonine found on signaling
      proteins, as well as a variety of small-molecule aryl and alkyl phosphates. It is
      unclear how DSPs accomplish similar reaction rates for phosphoesters, whose
      reactivity (i.e., pK(a) of the leaving group) can vary by more than 10(8). Here,
      we utilize the alkyl phosphate m-nitrobenzyl phosphate (mNBP), leaving-group
      pK(a) = 14.9, as a physiological substrate mimic to probe the mechanism and
      transition state of the DSP, Vaccinia H1-related (VHR). Detailed pH and kinetic
      isotope effects of the V/K value for mNBP indicates that VHR reacts with the
      phosphate dianion of mNBP and that the nonbridge phosphate oxygen atoms are
      unprotonated in the transition state. (18)O and solvent isotope effects indicate
      differences in the respective timing of the proton transfer to the leaving group
      and P-O fission; with the alkyl ester substrate, protonation is ahead of P-O
      fission, while with the aryl substrate, the two processes are more synchronous.
      Kinetic analysis of the general-acid mutant D92N with mNBP was consistent with
      the requirement of Asp-92 in protonating the ester oxygen, either in a step prior
      to significant P-O bond cleavage or in a concerted but asynchronous mechanism in
      which protonation is ahead of P-O bond fission. Collectively, the data indicate
      that VHR and likely all DSPs can match leaving-group potential with the timing of
      the proton transfer to the ester oxygen, such that diverse aryl and alkyl
      phosphoesters are turned over with similar catalytic efficiency.

PMID- 15236590
TI  - Mossbauer characterization of an unusual high-spin side-on peroxo-Fe3+ species in
      the active site of superoxide reductase from Desulfoarculus Baarsii. Density
      functional calculations on related models.
AB  - Superoxide reductase (SOR) is an Fe protein that catalyzes the reduction of
      superoxide to give H(2)O(2). Recently, the mutation of the Glu47 residue into
      alanine (E47A) in the active site of SOR from Desulfoarculus baarsii has allowed
      the stabilization of an iron-peroxo species when quickly reacted with H(2)O(2)
      [Mathe et al. (2002) J. Am. Chem. Soc. 124, 4966-4967]. To further investigate
      this non-heme peroxo-iron species, we have carried out a Mossbauer study of the
      (57)Fe-enriched E47A SOR from D. baarsii reacted quickly with H(2)O(2).
      Considering the Mossbauer data, we conclude, in conjunction with the other
      spectroscopic data available and with the results of density functional
      calculations on related models, that this species corresponds to a high-spin side
      on peroxo-Fe(3+) complex. This is one of the first examples of such a species in
      a biological system for which Mossbauer parameters are now available: delta(/Fe)
      = 0.54 (1) mm/s, DeltaE(Q) = -0.80 (5) mm/s, and the asymmetry parameter eta =
      0.60 (5) mm/s. The Mossbauer and spin Hamiltonian parameters have been evaluated
      on a model from the side-on peroxo complex (model 2) issued from the oxidized
      iron center in SOR from Pyrococcus furiosus, for which structural data are
      available in the literature [Yeh et al. (2000) Biochemistry 39, 2499-2508]. For
      comparison, similar calculations have been carried out on a model derived from 2
      (model 3), where the [CH(3)-S](1)(-) group has been replaced by the neutral
      [NH(3)](0) group [Neese and Solomon (1998) J. Am. Chem. Soc. 120, 12829-12848].
      Both models 2 and 3 contain a formally high-spin Fe(3+) ion (i.e., with empty
      minority spin orbitals). We found, however, a significant fraction (
      approximately 0.6 for 2, approximately 0.8 for 3) of spin (equivalently charge)
      spread over two occupied (minority spin) orbitals. The quadrupole splitting value
      for 2 is found to be negative and matches quite well the experimental value. The
      computed quadrupole tensors are rhombic in the case of 2 and axial in the case of
      3. This difference originates directly from the presence of the thiolate ligand
      in 2. A correlation between experimental isomer shifts for Fe(3+) mononuclear
      complexes with computed electron densities at the iron nucleus has been built and
      used to evaluate the isomer shift values for 2 and 3 (0.56 and 0.63 mm/s,
      respectively). A significant increase of isomer shift value is found upon going
      from a methylthiolate to a nitrogen ligand for the Fe(3+) ion, consistent with
      covalency effects due to the presence of the axial thiolate ligand. Considering
      that the isomer shift value for 3 is likely to be in the 0.61-0.65 mm/s range
      [Horner et al. (2002) Eur. J. Inorg. Chem., 3278-3283], the isomer shift value
      for a high-spin eta(2)-O(2) Fe(3+) complex with an axial thiolate group can be
      estimated to be in the 0.54-0.58 mm/s range. The occurrence of a side-on peroxo
      intermediate in SOR is discussed in relation to the recent data published for a
      side-on peroxo-Fe(3+) species in another biological system [Karlsson et al.
      (2003) Science 299, 1039-1042].

PMID- 15236591
TI  - Electrostatic control of the tryptophan radical in cytochrome c peroxidase.
AB  - Previously a K(+)-binding site, analogous to that found in ascorbate peroxidase
      (APX), was engineered into cytochrome c peroxidase (CcP) to test the hypothesis
      that the bound K(+) influences the stability of the Trp191 cation radical formed
      during the CcP catalytic cycle (Bonagura et al., (1996) Biochemistry 35, 6107 and
      Bonagura et al., (1999) Biochemistry 38, 5528). Characterization of this mutant,
      designated CcPK2, showed that the stability of the Trp191 cation radical is
      dependent on the occupancy of the engineered K(+) site and that the Trp191
      radical was much less stable in this mutant than in wild-type CcP. The mutations
      Met230Leu, Met231Gln, and Met172Ser have now been constructed on the CcPK2 mutant
      template to test if the Met residues also contribute to the stabilization of the
      Trp191 cation radical. Crystal structures show that the mutations affect only the
      local structure near the sites of mutation. Removal of these electronegative
      residues located less than 8 A from the Trp radical results in a further
      destabilization of the Trp radical. The characteristic EPR signal associated with
      the Trp radical is significantly narrowed and is characteristic of a tyrosine
      radical signal. Double-mixing stopped-flow experiments, where the delay time
      between the formation of CcP compound I and its mixing with horse heart
      ferrocytochrome c is varied, show that the stability of the Trp radical decreases
      as the Met residues are removed from the proximal cavity. When taken together,
      these results demonstrate a strong correlation between the experimentally
      determined stability of the Trp191 radical, the enzyme activity, and the
      calculated electrostatic stabilization of the Trp191 radical.

PMID- 15236592
TI  - Adenosine nucleotides and the regulation of GRP94-client protein interactions.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) serves essential roles in
      the regulation of signaling protein function, trafficking, and turnover. Hsp90
      function is intimately linked to intrinsic ATP binding and hydrolysis activities,
      the latter of which is under the regulatory control of accessory factors. Glucose
      regulated protein of 94 kDa (GRP94), the endoplasmic reticulum Hsp90, is highly
      homologous to cytosolic Hsp90. However, neither accessory factors nor adenosine
      nucleotides have been clearly implicated in the regulation of GRP94-client
      protein interactions. In the current study, the structural and regulatory
      consequences of adenosine nucleotide binding to GRP94 were investigated. We
      report that apo-GRP94 undergoes a time- and temperature-dependent tertiary
      conformational change that exposes a site(s) of protein-protein interaction; ATP,
      ADP, and radicicol markedly suppress this conformational change. In concert with
      these findings, ATP and ADP act identically to suppress GRP94
      homooligomerization, as well as both local and global conformational activity. To
      identify a role(s) for ATP or ADP in the regulation of GRP94-client protein
      interactions, immunoglobulin (Ig) heavy chain folding intermediates containing
      bound GRP94 and immunoglobulin binding protein (BiP) were isolated from myeloma
      cells, and the effects of adenosine nucleotides on chaperone-Ig heavy chain
      interactions were examined. Whereas ATP elicited efficient release of BiP from
      both wild-type and mutant Ig heavy chain intermediates, GRP94 remained in stable
      association with Ig heavy chains in the presence of ATP or ADP. On the basis of
      these data, we propose that structural maturation of the client protein
      substrate, rather than ATP binding or hydrolysis, serves as the primary signal
      for dissociation of GRP94-client protein complexes.

PMID- 15236593
TI  - Kinetics of dye efflux and lipid flip-flop induced by delta-lysin in
      phosphatidylcholine vesicles and the mechanism of graded release by amphipathic,
      alpha-helical peptides.
AB  - Delta-lysin is a 26-residue, amphipathic, alpha-helical peptide of bacterial
      origin. Its specificity is to some extent complementary to that of antimicrobial
      peptides. Therefore, understanding its mechanism is important for the more
      general goal of understanding the interaction of amphipathic peptides with
      membranes. In this article, we show that delta-lysin induces graded efflux of the
      contents of phosphatidylcholine vesicles. In view of this finding,
      carboxyfluorescein efflux kinetics were re-examined. In addition, peptide-induced
      lipid flip-flop was directly measured using fluorescence energy transfer between
      two lipid fluorophores initially placed on opposite leaflets of the bilayer.
      Carboxyfluorescein efflux and lipid flip-flop occur with essentially identical
      rate constants. On the basis of a detailed, quantitative analysis of the kinetics
      of peptide-vesicle interactions, we conclude that the peptide translocates across
      the bilayer as a small, transient aggregate, most likely a trimer. Dye efflux and
      lipid flip-flop occur concomitantly with the transient peptide-induced
      perturbation of the membrane. The experimental data are interpreted by comparing
      the predictions of the available models for the mechanism of action of
      amphipathic alpha-helical peptides. We demonstrate how the combination of the
      quantitative kinetic analysis, graded efflux, and reversibility of the peptide
      vesicle interaction can be used to reject several models for this particular
      peptide. Two models are compatible with the data, the toroidal pore model and the
      sinking raft model. On the basis of the small aggregate size, a trimer, the
      latter appears to be more plausible. Some significant modifications are
      introduced in the sinking raft model to take into account the new finding of
      graded dye release. Furthermore, we present an explanation for the phenomenon of
      graded release in general, which, contrary to all-or-none efflux, has not been
      well-understood.

PMID- 15236594
TI  - ER-60 domains responsible for interaction with calnexin and calreticulin.
AB  - ER-60 is a thiol oxidoreductase family protein of the endoplasmic reticulum that
      facilitates the oxidative folding of glycoproteins via interaction with calnexin
      (CNX) and calreticulin (CRT). In this study, we tried to identify the site of
      interaction with CNX and CRT in the ER-60 molecule. ER-60 was shown to be
      composed of at least four domains, named a, b, b', and a', by limited
      proteolysis. Recombinant fragments of ER-60, a, b', and a'c, were each expressed
      in Escherichia coli as an individual soluble folded protein that underwent a
      cooperative unfolding transition along a urea gradient. These fragments each gave
      the circular dichroism (CD) spectrum of the folded protein. On the other hand,
      fragment b, which did not undergo the cooperative unfolding transition along a
      urea gradient gel, did not show any sign of the folded structure on the CD
      measurement. However, subtraction of the spectra showed that the b domain was
      folded in wild-type ER-60 or abb'. Both a and a'c, which have a catalytic center
      CGHC motif, showed activity almost equivalent to half of that of wild-type ER-60.
      Extension from a or a'c to ab and abb' or b'a'c had little effect on their
      isomerase activity, suggesting that the b and b' domains hardly contribute to the
      catalytic activity of ER-60. The contribution of both the b and b' domains to the
      binding with CNX and CRT was revealed by surface plasmon resonance analysis and
      oxidative-refolding experiments of monoglucosylated RNase B with addition of the
      luminal domain of CNX.

PMID- 15236595
TI  - Kinetic characterization of thiolate anion formation and chemical catalysis of
      activated microsomal glutathione transferase 1.
AB  - Microsomal glutathione transferase 1 (MGST1) displays the unique ability to be
      activated, up to 30-fold, by the reaction with sulfhydryl reagents, e.g., N
      ethylmaleimide. Analysis of glutathione (GSH) thiolate formation, which occurs
      upon mixing activated MGST1 with GSH, reveals biphasic kinetics, where the rapid
      phase dominated at higher GSH concentrations. The kinetic behavior suggests a two
      step mechanism consisting of a rapid GSH-binding step (K(D)(GSH) approximately 10
      mM), followed by slower formation of thiolate (k(2) approximately 10 s(-1)). The
      release rate (or protonation of the enzyme GSH thiolate complex) of GS(-) was
      slow (k(-2) = 0.016 s(-1)), consistent with overall tight binding of GSH.
      Electrophilic second substrates react rapidly with the E*GS(-) complex, and
      again, a two-step mechanism is suggested. In comparison to the unactivated enzyme
      [Morgenstern et al. (2001) Biochemistry 40, 3378-3384], the mechanisms of GSH
      thiolate formation and electrophile interaction are similar; however, thiolate
      anion formation is enhanced 30-fold in the activated enzyme, contributing to an
      increased k(cat) (3.6 s(-1)). Interestingly, in the activated enzyme, thiolate
      formation and proton release from the enzyme are not strictly coupled, because
      proton release (as well as k(cat)) was found to be approximately 4 times slower
      than GSH thiolate formation in an unbuffered system. Solvent kinetic isotope
      effect measurements demonstrated a 2-fold decrease in the rate constant (k(2))
      for thiolate formation and k(cat) (in the reaction with 1-chloro-2,4
      dinitrobenzene) for both unactivated and activated MGST1. This indicates that
      thiolate formation contributes to k(cat) for the activated enzyme, as suggested
      previously for unactivated MGST1. The stoichiometry of thiolate formation, proton
      release, and burst kinetics suggested utilization of one GSH molecule per enzyme
      trimer.

PMID- 15236596
TI  - Common chromatin architecture, common chromatin remodeling, and common
      transcription kinetics of Adr1-dependent genes in Saccharomyces cerevisiae.
AB  - The chromatin structure of several Saccharomyces cerevisiae ADR1-dependent genes
      was comparatively analyzed in vivo in order to evaluate the role of promoter
      architecture in transcriptional control. In repressing conditions (high glucose)
      a nucleosome particle always obstructs the TATA box, immediately adjacent to an
      upstream-located nucleosome-free region containing a cluster of Adr1 binding
      sites. Upon derepression the TATA box-containing nucleosome is destabilized
      according to a mechanism shared by all of the genes studied. The transcription
      factor Adr1 is always required for the observed chromatin remodeling. mRNA
      accumulation of all of the genes analyzed is strongly delayed in the absence of
      the acetyltransferase Gcn5 and is decreased in the presence of a temperature
      sensitive Esa1 mutant. The results suggest that a defined promoter chromatin
      structure, controlled by DNA conformational features, is relevant for the
      activation of coregulated genes.

PMID- 15236597
TI  - Human deoxyribonucleases.
AB  - Although mammalian deoxyribonucleases were discovered more than 60 years ago,
      interest in these enzymes is not weakening. During the last decade, intensive
      studies of human DNases culminated in discovery of several novel enzymes
      exhibiting DNase activity. These include an unusual DNase, lactoferrin. For some
      enzymes, their three-dimensional structure and molecular mechanisms underlying
      their functioning have been elucidated. In patients with some autoimmune and
      viral diseases, catalytic antibodies also contribute to alternative pathways of
      DNA hydrolysis. Some enzymes exhibiting DNase activity play an important role in
      pathogenesis of various diseases and also in programmed cell death (apoptosis).
      This review highlights recent achievement in human deoxyribonuclease research. It
      also considers mechanisms of DNA hydrolysis. The review also summarizes modern
      data on the biological role of these enzymes in functioning of the human
      organism, realization of its protective mechanisms, and possible applications of
      DNases in medicine.

PMID- 15236598
TI  - Disaggregation of platelet aggregates formed by the action of thrombin in the
      presence of hydrogen peroxide.
AB  - The aggregation and change in the intracellular Ca2+ concentration induced by
      thrombin (0.005-0.22 U/ml) in the presence of H2O2 (0.05-0.6 mM) was
      investigated. Under the chosen experimental conditions (incubation time of
      platelets with H2O2 not more than 15 sec), H2O2 neither accelerated nor inhibited
      the thrombin-induced platelet aggregation. However, platelet aggregates formed by
      the action of thrombin in the presence of H2O2 were unstable and disaggregated.
      Disaggregation was abolished by catalase added after thrombin. The disaggregation
      effect was dose-dependent; the process of disaggregation was confirmed by
      electron microscopy. Hydrogen peroxide did not influence thrombin-induced
      increase in the intracellular Ca2+ concentration, but dose-dependently
      accelerated Ca2+ extrusion from the platelet cytoplasm.

PMID- 15236599
TI  - General stress protein CTC from Bacillus subtilis specifically binds to ribosomal
      5S RNA.
AB  - Two recombinant proteins of the CTC family were prepared: the general stress
      protein CTC from Bacillus subtilis and its homolog from Aquifex aeolicus. The
      general stress protein CTC from B. subtilis forms a specific complex with 5S rRNA
      and its stable fragment of 60 nucleotides, which contains internal loop E. The
      ribosomal protein TL5 from Thermus thermophilus, which binds with high affinity
      to 5S rRNA in the loop E region, was also shown to replace the CTC protein from
      B. subtilis in its complexes with 5S rRNA and its fragment. The findings suggest
      that the protein CTC from B. subtilis binds to the same site on 5S rRNA as the
      protein TL5. The protein CTC from A. aeolicus, which is 50 amino acid residues
      shorter from the N-terminus than the proteins TL5 from T. thermophilus and CTC
      from B. subtilis, does not interact with 5S rRNA.

PMID- 15236600
TI  - Predominant protection of D2-protein against photodestruction in isolated
      D1/D2/cytochrome b559 by K15, a phenolic-type inhibitor of electron transfer in
      photosystem 2.
AB  - A protective action of K15 (4-[methoxy-bis(trifluoromethyl)methyl]-2,6
      dinitrophenylhydrazone methyl ketone), an inhibitor of electron transport in
      photosystem 2 (PS 2), against photoinactivation of the PS 2 reaction center (RC)
      D1/D2/cytochrome b(559) complex, isolated from pea chloroplasts, by red light
      (0.7 mmol photons/sec per m(2)) has been investigated under aerobic conditions.
      The inhibitor K15 causing cyclic electron transfer around PS 2 and thus
      prohibiting stabilization of separated charges has been shown to effectively
      protect RC both against the loss of photochemical activity (measured as
      reversible photoinduced absorbance changes related to photoreduction of
      pheophytin) and aggregation and degradation of the proteins D2 and D1 during
      photoinactivation. Comparison of the protective action of K15 and of another
      inhibitor of electron transfer in PS 2, diuron, against light-induced destruction
      of proteins D1 and D2 shows that diuron stabilizes protein D1 and K15 stabilizes
      protein D2. The preferential protection of D2 against photoinduced destruction
      revealed in our work is in accord with the concept of a specific binding of K15
      with this protein. It is proposed that this binding site may be that of the
      primary quinone electron acceptor Q(A) located on the D2 protein (in contrast to
      diuron, which is known to replace the secondary electron acceptor Q(B) from its
      binding site on D1).

PMID- 15236601
TI  - Interaction of polymer aggregates based on stearoyl-poly-N-vinylpyrrolidone with
      blood components.
AB  - Stearoyl-poly-N-vinylpyrrolidone (PVP-stear) of various molecular weights (M(n) =
      1500-5500) self-assemble in aqueous medium. Particles prepared from PVP-stear
      were characterized in terms of shape and size distribution, and the mechanical
      stability of the particles was studied. The interaction of PVP-stear and its
      aggregates with blood components was investigated. Aggregates formed by the
      polymers with M(n) = 1500-3500 in the presence of human serum are stable. The
      direct lytic action of PVP-stear preparations was studied using sheep and human
      erythrocytes. The influence of PVP-stear aggregates on the activation of
      complement system both on classical and alternative pathways was examined. The
      aggregates prepared from PVP-stear of various molecular weights had no effect on
      the activation of the complement system.

PMID- 15236602
TI  - Analysis of serotonin transporter in human platelets by immunoblotting using site
      specific antibodies.
AB  - We have produced a panel of site-specific antibodies recognizing different
      regions of the human serotonin transporter (SERT). This panel included: 1)
      monoclonal antibodies 23C5 (mAbs 23C5) to the C-terminal region (amino acid
      residues 597-630); 2) polyclonal antibodies (pAbs) to the N-terminal region
      (amino acid residues 69-83); 3) pAbs to the region (amino acid residues 86-100)
      in the beginning of the first transmembrane domain (TMD). The antibodies were
      produced using recombinant proteins and synthetic peptides (containing certain
      sequences of SERT) as antigens. These antibodies were purified by affinity
      chromatography, conjugated to horseradish peroxidase (HRP), and used for
      immunoblotting analysis of SERT in extracts of human platelets. Sodium dodecyl
      sulfate extracts were prepared under conditions preventing non-specific
      proteolytic degradation of the proteins. In platelet extracts, all antibodies
      were able to detect the 67 kD protein, apparently corresponding to full-length
      SERT molecule (its theoretical mass is about 70 kD). These antibodies also
      detected several polypeptides of smaller size (56, 37, 35, 32, 22, and 14 kD),
      apparently corresponding to N-terminal, C-terminal, and non-terminal SERT
      fragments. Specificity of immunostaining was confirmed by preincubation of HRP
      labeled anti-SERT antibodies with excess of corresponding antigen, which resulted
      in disappearance of protein band staining. It is suggested that SERT undergoes a
      programmed proteolytic cleavage (processing) resulting in formation of several
      SERT-derived polypeptides of smaller size. It is possible that one of the cleaved
      SERT species is required for serotonin transport activity. Possible sites for
      specific proteolysis may be located in the region near TMD1 and in the
      intracellular loop between TMD4 and TMD5.

PMID- 15236603
TI  - Cloning and expression of catalytic subunit of MLIII, the ribosome-inactivating
      protein from Viscum album.
AB  - We have cloned the gene encoding a precursor of mistletoe (Viscum album) toxin
      MLIII. Analyses of nucleotide and deduced amino acid sequences of this gene
      revealed significant differences between MLI and MLIII preprotoxin genes.
      Immunochemical properties of recombinant A-subunit expressed in Escherichia coli
      and renatured were investigated using a panel of monoclonal antibodies raised
      against three mistletoe toxins (MLI, MLII, and MLIII). Ribosome-inactivating
      activity of recombinant MLIII A-subunit was detected in cell-free lysate of
      rabbit reticulocytes.

PMID- 15236604
TI  - Assembly of pigment-protein complexes in carotenoid-deficient membranes of
      plastids from wheat seedlings treated with norflurazon.
AB  - The pyridazinone-type herbicide norflurazon SAN 9789 inhibiting the biosynthesis
      of long-chain carotenoids results in significant decrease in PS II core complexes
      and content of light-harvesting complex (LHC) polypeptides. At the same time,
      early light-induced proteins (ELIP) with molecular masses of 20.5-16.5 and 13.5
      kD disappear in norflurazon-treated seedlings grown under intermittent (pulsed)
      light, confirming the hypothesis that they are carotenoid-binding proteins. Full
      disappearance of Chl a forms at 668, 676, and 690 nm and a sharp decrease in Chl
      b form at 648 nm in treated seedlings grown under 30 or 100 lx light intensity
      shows close contact of these forms with carotenoids in the thylakoid membrane.
      The band shift from 740 to 720 nm in the low-temperature fluorescence spectrum
      (77 K) suggests a disturbance of energy transfer from LHC to the Chl a form at
      710-712 nm.

PMID- 15236605
TI  - Cell wall teichoic acids of two Brevibacterium strains.
AB  - Structurally identical teichoic acids were detected in cell walls of two soil
      isolates assigned to Brevibacterium linens based on phylogenetic data. Both cell
      walls contain unsubstituted 1,3-poly(glycerol phosphate) and
      poly(glycosylglycerol phosphate). Repeating units of the latter--alpha-D-GlcpNAc
      (1-->4)-beta-D-Galp-(1-->1)-Gro--are bound by phosphodiester bonds including OH-3
      of galactose and OH-3 of glycerol. Some of the N-acetylglucosamine residues have
      4,6-pyruvic acid acetal, amounts of the latter in the two strains being unequal.
      Species-specificity of the structures of teichoic acids in the genus
      Brevibacterium is discussed.

PMID- 15236606
TI  - Expression and role of integrins in invasive activity of oncotransformed
      fibroblasts differing in spontaneous metastasizing.
AB  - Four closely related lines of RSV-transformed Syrian hamster fibroblasts
      differing drastically in their spontaneous metastatic capacity were investigated
      for the surface expression of integrins, in vitro invasion, and production of MMP
      2 collagenase. The highly metastasizing HET-SR-2SC-LNM cells differ from the
      lowly metastasizing parental HET-SR cells in a high level of the surface
      expression of the collagen-specific alpha1beta1, alpha2beta1, and alphavbeta3
      integrins, a high invasive activity, and an increased production of MMP-2. The
      same properties are characteristic for the actively metastasizing cells of the
      independent HET-SR-1 line. The lowly metastasizing fibroblasts that are derived
      from HET-SR-2SC-LNM retain a high level of the expression of the alpha1beta1 and
      alpha2beta1 integrins, but, unlike the parental line, they exhibit a decreased
      expression of the alphavbeta3 integrin, invasion in Matrigel, and MMP-2
      production. Substrate stimulation of the signal function of the collagen-specific
      integrins increases the production of MMP-2 by the metastatically active
      fibroblasts. Inhibition of the signal activity of the integrins by RGD-containing
      pentapeptide or by genistein reduces markedly in vitro invasion in Matrigel and
      MMP-2 production. The role of specific properties of the extracellular matrix
      surrounding tumor cells and of specific surface integrins expressed in these
      cells in developing of the malignant phenotype is discussed.

PMID- 15236607
TI  - Cloning and sequencing of the gene of tryptophan-7-halogenase from Pseudomonas
      fluorescens strain CHA0.
AB  - The gene of tryptophan-7-halogenase from the Pseudomonas fluorescens strain CHA0,
      a producer of the halogenated antibiotic pyrrolnitrin, has been cloned and
      sequenced.

PMID- 15236608
TI  - Features of the uncoupling effect of fatty acids in liver mitochondria of mammals
      with different body weight.
AB  - In the presence of oligomycin, EGTA, and magnesium ions, the protonophore
      uncoupling activity of palmitate (V(Pal)) is determined as the ratio of the
      acceleration of respiration with palmitate to its concentration. Under these
      conditions, V(Pal) in liver mitochondria of one-month-old rats with the body
      weight of 50 g is 1.46-fold higher than in liver mitochondria of adult rats with
      the body weight of 250 g, whereas the uncoupling activity of FCCP does not depend
      on the age of the animals. The difference in V(Pal) is mainly due to its
      component insensitive to carboxyatractylate and glutamate (V(Ins)). This value is
      2.9-fold higher in mitochondria of one-month-old rats than in those of adult
      rats. The protonophore activity of palmitate is similar in liver mitochondria of
      four-day-old and adult rats. In liver mitochondria of adult mammals (mouse, rat,
      guinea pig, rabbit), V(Pal) decreases with increase in the body weight of the
      animals. In double logarithmic coordinates, the dependence of the V(Pal) value on
      the body weight is linear with slope angle tangent of -0.18. The V(Pal) value is
      mainly contributed by its component V(Ins). In the presence of calcium ions,
      palmitate induces the nonspecific permeability of the inner membrane of liver
      mitochondria (pore opening). This Ca2+-dependent uncoupling effect of palmitate
      is less pronounced in mitochondria of one-month-old rats than in those of adult
      rats. In mitochondria of adult animals (mice, rats, and guinea pigs), the Ca2+
      dependent uncoupling activity of palmitate is virtually the same. It is concluded
      that the protonophore uncoupling effect of palmitate in liver mitochondria of
      mammals, unlike its Ca2+-dependent effect, is associated with thermogenesis at
      rest and also with production of additional heat on cooling of the animals.

PMID- 15236609
TI  - Temperature dependent protease activity and structural properties of human HtrA2
      protease.
AB  - Human HtrA2 belongs to a new class of oligomeric serine protease, members of
      which are found in most organisms. Mature HtrA2 is released from mitochondria
      into the cytosol in response to apoptotic stimuli. In this report, the effect of
      temperature on proteolytic activity of HtrA2 and related structural properties
      were investigated. In the range from 25 to 55 degrees C, the proteolytic activity
      of HtrA2 rapidly increased with temperature, and it drastically decreased at and
      over 60 degrees C. Structural analysis using far-UV CD spectroscopy and gel
      filtration revealed no significant change in the secondary structure of HtrA2
      from 25 to 70 degrees C, or in the oligomeric size between 25 and 55 degrees C.
      However, a significant change at the tertiary level, as examined using near-UV
      CD, was observed for HtrA2 in the range from 25 to 60 degrees C. Differential
      scanning calorimetry indicated that HtrA2 exhibits a thermal transition beginning
      at around 61 degrees C. The fluorescence intensity of ANS interacting with HtrA2
      decreased with increasing temperature. HtrA2 was found to be able to complement
      DegP function at 44 degrees C, indicating that HtrA2 could have protective
      functions in mitochondria.

PMID- 15236610
TI  - Plasma trace elements, vitamin B12, folate, and homocysteine levels in cirrhotic
      patients compared to healthy controls.
AB  - Increased serum homocysteine (Hcy) can induce liver diseases and can play a
      remarkable role in hepatic disorders. The purpose of the present study therefore
      was to investigate the relationship between serum vitamin B(12), folate, zinc and
      copper, cysteine, and Hcy level differences between cirrhotic patients and
      healthy subjects. We studied 32 cirrhotic patients (12 females and 20 males) aged
      45 +/- 11 years and 32 control subjects (12 females and 20 males) aged 39 +/- 9
      years. There was an inverse correlation between Hcy and vitamin B(12) in controls
      (r = -0.442, p < 0.011) but not in cirrhotic patients (r = -0.147, not
      significant). Also, mean plasma folate was decreased in cirrhotic patients
      compared to controls (p < 0.001). Copper increased whereas zinc decreased
      significantly in cirrhotic patients. A positive correlation was seen between the
      Cu/Zn ratio and Cu in controls (r = 0.690, p < 0.01), but the correlation between
      the Cu/Zn ratio and Cu was not significant in the cirrhotic group. Negative
      correlations were seen between plasma concentration of zinc and the Cu/Zn ratio
      in controls and cirrhotic patients (r = -0.618, p < 0.01 and r = -0.670, p <
      0.01, respectively). Cirrhotic patients displayed multiple abnormalities,
      including changes in cysteine metabolism and in zinc and copper levels. Although
      hyperhomocysteinemia is known as an atherogenic and thrombogenic risk factor for
      cardiovascular disease, it might also be a risk factor for cirrhotic patients.
      Plasma Hcy, vitamin B(12), and folic acid measurement may be useful in the
      evaluation of cirrhotic patients.

PMID- 15236611
TI  - New aspartic proteinase of Ulysses retrotransposon from Drosophila virilis.
AB  - This work is focused on the investigation of a proteinase of Ulysses mobile
      genetic element from Drosophila virilis. The primary structure of this proteinase
      is suggested based on comparative analysis of amino acid sequences of aspartic
      proteinases from retroviruses and retrotransposons. The corresponding cDNA
      fragment has been cloned and expressed in E. coli. The protein accumulated in
      inclusion bodies. The recombinant protein (12 kD) was subjected to refolding and
      purified by affinity chromatography on pepstatin-agarose. Proteolytic activity of
      the protein was determined using oligopeptide substrates melittin and insulin B
      chain. It was found that the maximum of the proteolytic activity is displayed at
      pH 5.5 as for the majority of aspartic proteinases. We observed that hydrolysis
      of B-chain of insulin was totally inhibited by pepstatin A in the micromolar
      concentration range. The molecular weight of the monomer of the Ulysses
      proteinase was determined by MALDI-TOF mass-spectrometry.

PMID- 15236612
TI  - HIV remains a deadly disease.

PMID- 15236614
TI  - Fatherhood and HIV-positive heterosexual men.
AB  - OBJECTIVES: The study of HIV and issues of reproduction is women-focused. HIV
      positive men are overlooked and understudied. This study examined views on
      reproduction of heterosexual HIV-positive men. METHODS: Systematic questionnaire
      data were gathered from HIV-positive men (n=32) attending an HIV clinic in
      London. RESULTS: Heterosexual men were rarely given medical advice on
      reproduction (only 9.4%). Few felt fully informed (21.9%), while many felt
      uninformed (46.9%) or needed more information (28.1%). Over half would value
      fertility/fathering consultations, up-to-date information and quick referral to
      fertility clinics. Nearly half (43.8%) had considered having children and 37.5%
      had had a child prior to HIV diagnosis. HIV status affected views on fathering,
      and the advent of new treatments changed views in over half of the men. Almost
      half (41%) believed they would experience discrimination if they conceived a baby
      and a quarter would withhold their HIV status when attending antenatal clinics.
      The majority (81%) believed that a child gave meaning to life and something to
      live for - only 3.1% felt a child would be a burden. Most men overestimated
      potential vertical transmission and would value time to discuss fathering and
      fatherhood. CONCLUSIONS: There are gaps in provision. The majority of men felt
      that children gave meaning to life and a reason to live. Reproduction issues are
      not raised with HIV-positive men who are uninformed and unclear where to turn for
      information. Fatherhood should not be shunned as an issue for all HIV-positive
      men.

PMID- 15236613
TI  - Hepatic pathology in AIDS: a pathological study from Mumbai, India.
AB  - OBJECTIVES: To assess the spectrum of hepatic disorders in AIDS, liver specimens
      from 171 patients (155 autopsies and 16 biopsies) were reviewed. METHODS: A
      retrospective and prospective study of 171 autopsy and biopsy specimens was
      carried out at a tertiary level hospital in Mumbai, India. RESULTS: Of the
      patients included in the study, 127 (74%) were male and 44 (26%) were female. The
      heterosexual route was the predominant mode of HIV transmission, identified in
      163 (95%) patients. A total of 99 of 171 patients (58%) showed significant
      pathological lesions, and the most common pathological processes involving the
      liver appeared to be secondary to infections. None of our patients showed
      isolated infectious diseases of the liver. The spectrum of liver diseases
      identified was as follows: tuberculosis in 70 patients (41%), cryptococcosis in
      eight (5%), cytomegalovirus infection in six (3%), hepatitis B infection in five
      (3%), candidiasis in one (0.5%), malaria in one (0.5%), cirrhosis in six (3%),
      amyloidosis in one (0.5%) and primary hepatic lymphoma in one (0.5%).
      CONCLUSIONS: AIDS patients were found to have a high prevalence of underlying
      hepatic abnormalities. The spectrum of disease among patients with AIDS in India
      differs from that in developed countries. Our results suggest that hepatic
      tuberculosis is more common in AIDS than previously recognized, and that liver
      specimens should be examined routinely for the presence of acid-fast bacilli.

PMID- 15236615
TI  - Association of highly active antiretroviral therapy failure with chemokine
      receptor 5 wild type.
AB  - OBJECTIVES: Approximately 10% of HIV-infected patients fail to respond properly
      to highly active antiretroviral therapy (HAART). Among other factors, genetic
      variants of chemokine receptors have been shown to modify the course and outcome
      of HIV infection. Our objective was to investigate whether a failure of
      virological response is associated with polymorphisms of the chemokine receptors
      or cofactors. METHODS: A total of 256 HIV-infected patients receiving HAART and
      221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Delta32
      bp, stromal derived factor 1 (SDF1)-3'A and chemokine receptor 2 (CCR2)-64I
      polymorphisms. Treatment failure was defined as failure to lower the viral load
      below 50 HIV-1 RNA copies/mL within the first year of treatment despite good
      adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and
      amplified by polymerase chain reaction (PCR). RESULTS: Successful treatment was
      associated with heterozygosity for the CCR5-Delta32-bp variant found in 24 of 184
      responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184
      responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the
      SDF1-3'A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups:
      4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for
      successful treatment was 4.7 for individuals who tested positive for at least one
      variant allele of the three polymorphisms. Comparison of genotype frequencies
      between HIV-infected and healthy individuals showed highly significant
      differences (P<0.001). CONCLUSIONS: Chemokine receptor polymorphisms have a
      modifying effect on the virological response to HAART. Multivariate analysis
      demonstrated that heterozygosity for the CCR5-Delta32-bp variant is an
      independent prognostic factor for treatment outcome.

PMID- 15236617
TI  - A prospective multicentre study of discontinuing prophylaxis for opportunistic
      infections after effective antiretroviral therapy.
AB  - OBJECTIVE: To assess the medium-term safety of discontinuing prophylaxis (primary
      or secondary) for opportunistic infections following an effective response to
      antiretroviral therapy. METHODS: Participating clinical sites prospectively
      identified patients in whom the discontinuation of prophylaxis for any
      opportunistic infection was considered to be clinically indicated, although CD4
      levels were not predefined. A follow-up report was subsequently sent every 6
      months requesting information on changes in prophylaxis, antiretroviral drugs,
      new AIDS-defining events, and CD4 cell count results. RESULTS: Prophylaxis for
      Pneumocystis carinii pneumonia (PCP) was withdrawn in 524 patients (426 primary
      and 98 secondary prophylaxis), prophylaxis for Mycobacterium avium complex (MAC)
      was withdrawn in 28 patients (13 primary and 15 secondary), and prophylaxis for
      cytomegalovirus (CMV) retinitis was withdrawn in 10 patients. CD4 counts were
      generally maintained above accepted prophylaxis threshold levels during the
      period of follow up (95-98% of the time). Total follow up to last report or re
      continuation of prophylaxis was 680 and 144 person-years for patients
      discontinuing primary and secondary PCP prophylaxis, respectively. No cases of
      PCP were reported, giving incidence rates of 0.0 (upper 95% confidence limit 0.4)
      and 0.0 (2.1) per 100 person-years. No cases of MAC were reported, but one
      patient had a recurrence of CMV retinitis. PCP prophylaxis was restarted in 30
      patients; no patients restarted MAC or CMV prophylaxis. CONCLUSIONS: Previous
      studies have demonstrated a low risk of PCP in the short term following the
      withdrawal of prophylaxis in patients who have responded well to antiretroviral
      therapy. The present study suggests a continuing low level of risk with extended
      follow up, provided adequate CD4 count levels are maintained. The case of
      recurrent CMV retinitis in a patient with impressive immunological and
      virological response indicates the need for close monitoring of patients
      previously diagnosed with this condition.

PMID- 15236616
TI  - Characteristics of patients diagnosed with AIDS shortly after first detection of
      HIV antibodies in Lyon University hospitals from 1985 to 2001.
AB  - A diagnosis of AIDS shortly after the detection of HIV antibodies suggests a long
      lasting course of the disease without care. The factors associated with a short
      delay between the initial HIV-1-positive test and the first AIDS-defining event
      were identified in 1901 patients from 1985 to 2001 in Lyon University hospitals.
      A total of 576 individuals (30.3%) had an interval of </=3 months between the
      detection of HIV infection and AIDS. The factors independently associated with a
      delay of </=3 months were: age from 30 to 44 years [odds ratio (OR) 2.5; 95%
      confidence interval (CI) 1.9-3.2]; age from 45 to 59 years (OR 5.6; 95% CI 3.9
      7.8); age >/=60 years (OR 4.5; 95% CI 2.5-8.1), compared to those<30 years old;
      heterosexuality (OR 2.4; 95% CI 1.6-3.4); injection drug use (OR 2.1; 95% CI 1.5
      2.7); and other exposures (OR 2.4; 95% CI 1.6-3.4), compared to homosexual
      exposure; two opportunistic infections at AIDS (OR 1.8; 95% CI 1.4-2.4) compared
      to one; and Pneumocystis carinii pneumonia as initial AIDS event (OR 2.6; 95% CI
      1.8-3.7), compared to Kaposi's sarcoma. These results provide opportunities to
      refocus local public health interventions to reduce delayed access to care.

PMID- 15236619
TI  - Causes of death among patients with HIV in Singapore from 1985 to 2001: results
      from the Singapore HIV Observational Cohort Study (SHOCS).
AB  - OBJECTIVES: To investigate the major primary and contributory causes of death
      among HIV patients in Singapore. DESIGN: A retrospective observational cohort
      study of all adult patients seen at the national referral centre for HIV in
      Singapore between 1985 and 2001. METHODS: Data were extracted from the patients'
      records by 10 trained health care workers. AIDS-defining conditions were
      established using predefined criteria. For each case, a single principal cause of
      death and up to three contributory causes were identified. RESULTS: A total of
      1504 patients aged 17 years or over were seen before the end of 2001, of whom 504
      have died. The most frequent principal causes of death were Mycobacterium avium
      (17.5%), Mycobacterium tuberculosis (9.7%), pneumonia (cause unknown) (6.5%) and
      Cryptococcus neoformans (6.7%). Three hundred and eighteen patients (63.1%) died
      from an AIDS-defining condition. CONCLUSIONS: The causes of death were similar to
      those found in Western cohorts, except that disseminated M. avium was a more
      frequent cause of death.

PMID- 15236618
TI  - Efficacy, safety and predictive factors of virological success of a boosted
      amprenavir-based salvage regimen in heavily antiretroviral-experienced HIV-1
      infected patients.
AB  - BACKGROUND: Amprenavir (APV) has been shown to be effective in naive or treatment
      experienced HIV-1 infected patients. However, the safety and efficacy of the APV
      600 mg/ritonavir (RTV) 100 mg twice a day (bid) combination, the usually
      recommended dosage for boosted APV, have been less well studied. We assessed the
      predictive factors associated with virological success of APV/RTV-based regimens.
      METHODS: Patients in the PharmAdapt study receiving an APV/RTV-containing regimen
      were included in the study. The predictivity of covariates on virological
      response at 4 months was analysed according to the data analysis plan. We
      processed logistic regression using bootstrapping to allow several covariates in
      the models. RESULTS: Forty patients received an APV/RTV-containing regimen, 38 of
      whom were male (95%). Risk factors were heterosexual contacts (four patients;
      10%), homosexual contacts (31 patients; 78%), and intravenous drug use (four
      patients; 10%). Twenty-seven per cent of patients were Centers for Disease
      Control and Prevention Classification System (CDC) stage A, 38% were stage B and
      35% were stage C. The median baseline CD4 count was 313 cells/microL
      [interquartile range (IQR) 211, 414], and the median baseline viral load was 4.4
      log(10) HIV-1 RNA copies/mL (IQR 3.7, 4.9). Patients were exposed to a median
      number of 7.5 (IQR 6, 9) drugs for a median number of 3.8 (IQR 3.3, 4.3) years.
      The baseline number of resistance mutations was 4 [IQR 3, 5 for nucleoside
      reverse transcriptase inhibitors (NRTIs), 1 (IQR 0, 2)] for non-nucleoside
      reverse transcriptase inhibitors (NNRTIs) and 6 [IQR 5, 8 for protease inhibitors
      (PIs)]. At month 4, median viral load decreased to 1.2 log(10) copies/mL (IQR
      0.3, 1.6); 50% of patients had a viral load<200 copies/mL by intention-to-treat
      analysis. The number of APV resistance mutations was associated with viral load
      changes. Median APV concentration was 1750 ng/mL (IQR 1130, 2520). At month 4,
      using several cut-offs, neither APV concentration nor the genotypic inhibitory
      quotient was predictive of viral load changes. Baseline viral load and the number
      of protease mutations were associated with outcome. CONCLUSIONS: Efficacious APV
      concentrations need to be determined for antiretroviral-experienced patients.
      Baseline viral load and the number of mutations on the protease coding region
      (PRO) were associated with the virological outcome of APV/RTV-based regimens.

PMID- 15236620
TI  - A randomized study investigating the efficacy and safety of amprenavir in
      combination with low-dose ritonavir in protease inhibitor-experienced HIV
      infected adults.
AB  - OBJECTIVES: To compare the safety and efficacy of amprenavir [APV/j Agenerase
      trade mark; GlaxoSmithKline, [Ware, UK; 600 mg twice a day (bid)] boosted with
      low-dose ritonavir (RTV, 100 mg bid) with those of other protease inhibitors
      (PIs) in PI-experienced HIV-infected patients. STUDY DESIGN: Parallel-group,
      randomized, open-label, multicentre study. METHODS: One hundred and sixty-three
      patients with HIV predicted to be sensitive to APV, another PI and a nucleoside
      reverse transcriptase inhibitor (NRTI) were randomly assigned to receive either
      APV boosted with low-dose RTV (APV/r) or a standard of care (SOC) PI with or
      without low-dose RTV. The non-inferiority of APV/r to the SOC PIs was assessed by
      time-weighted average change from baseline (AAUCMB) in plasma viral load (vRNA)
      at week 16. RESULTS: The antiviral response for APV/r bid was non-inferior to
      that for the SOC PI group: the vRNA AAUCMB mean treatment difference was 0.043
      log(10) HIV-1 RNA copies/mL [95% confidence interval (CI)-0.250, 0.335]. APV/r
      bid was generally well tolerated. CONCLUSIONS: Results confirm the antiviral
      activity, short-term safety and tolerability of APV/r bid in PI-experienced
      patients.

PMID- 15236621
TI  - Acute hepatitis C in HIV-infected men who have sex with men.
AB  - BACKGROUND: Hepatitis C virus (HCV) is usually transmitted via the parenteral
      route, but there are widely discrepant findings on its possible sexual
      transmission. Thus there are no recommendations concerning protected sex for
      couples in which only one partner is HCV-infected. Whether HIV or other sexually
      transmitted diseases could favour HCV transmission remains unclear, but recent
      data suggesting an increasing incidence of acute HCV in HIV-infected men
      underline the major public health implications of this issue. CASE REPORTS:
      Between June 2002 and July 2003, five HIV-infected homosexually active men
      presented with primary (n=4) and secondary (n=1) syphilis and concomitant
      abnormal liver function tests revealing acute asymptomatic HCV seroconversion.
      Other causes of acute viral hepatitis were inquired into and excluded. Highly at
      risk sexual behaviour, including unprotected anal intercourse and unsafe oral
      sex, with concomitant syphilis, was found to be the only identifiable important
      risk factor for transmission of HCV. CONCLUSIONS: Sexual transmission may be
      fuelling a significant increase in HCV seroconversions among HIV-infected men who
      have highly risky sexual behaviours. Given the recent data suggesting the spread
      of sexually transmitted infections among HIV-infected gay men, specific
      recommendations concerning safe sex are urgently needed.

PMID- 15236622
TI  - Determination of indinavir and nelfinavir trough plasma concentration efficacy
      thresholds according to virological response in HIV-infected patients.
AB  - BACKGROUND: There is evidence to suggest a pharmacokinetic-pharmacodynamic
      relationship in HIV-infected patients receiving protease inhibitor (PI)
      containing highly active antiretroviral therapy (HAART); however, the effective
      trough PI plasma concentrations achieved have not been precisely determined.
      METHODS: The relationship between HIV viral load and concomitant PI trough plasma
      concentration (C(trough)) was evaluated in 101 patients receiving at least 4
      months of thrice daily indinavir (IDV)-containing (n=68) or nelfinavir (NFV)
      containing (n=33) HAART. The more discriminating C(trough) efficacy thresholds
      were determined statistically for each PI by using the raw C(trough) and the time
      corrected C(trough), using the precise delay since the last PI intake and the
      half-life of each PI. RESULTS: For IDV (P=0.002) and NFV (P=0.019) median
      C(trough) levels were higher in patients with undetectable viral load [0.23 mg/L
      (n=30) and 2.3 mg/L (n=16) respectively] than in patients with detectable viral
      load [0.11 mg/L (n=38) and 0.6 mg/L (n=17) respectively]. C(trough) levels of IDV
      (r=-0.45; P<0.0001) and NFV (r=-0.43; P=0.011) were correlated with the
      concomitant viral load. The more discriminating C(trough) efficacy thresholds
      were estimated statistically as 0.12 mg/L for IDV and 0.5 mg/L for NFV. When
      C(trough) values were time-corrected, the C(trough) efficacy thresholds, 8 h
      after the last intake, were 0.15 mg/L for IDV and 0.65 mg/L for NFV. CONCLUSIONS:
      These results support the importance of achieving minimal effective C(trough) to
      improve the virological efficacy of PI-containing HAART, and specify the target
      concentrations for IDV and NFV.

PMID- 15236624
TI  - Impact of oxidative stress on neuronal survival.
AB  - 1. Reactive oxygen species and oxidative state are slowly gaining acceptance in
      having a physiological relevance rather than just being the culprits in
      pathophysiological processes. The control of the redox environment of the cell
      provides for additional regulation in relation to signal transduction pathways.
      Conversely, aberrant regulation of oxidative state manifesting as oxidative
      stress can predispose a cell to adverse outcome. 2. The phosphatidylinositol 3
      kinase/akt pathway is one such pathway that is partially regulated via oxidative
      state and, in an oxidative stress paradigm such as ischaemic-reperfusion injury,
      may be inactivated, which can lead to exacerbation of cell death. 3. Activation
      of nuclear factor (NF)-kappaB has been associated with oxidative stress. The role
      of NF-kappaB in neuronal cell death is widely debated, with major studies
      highlighting both a pro- and anti-apoptotic role for NF-kappaB, with the outcome
      being region, stimulus, dose and duration specific. 4. Oxidative state plays a
      key role in the regulation and control of numerous signal transduction pathways
      in the cell. Elucidating the mechanisms behind oxidative stress-mediated neuronal
      cell death is important in identifying potential putative targets for the
      treatment of diseases such as stroke.

PMID- 15236625
TI  - Oxidized low-density lipoprotein induces endothelial progenitor cell senescence,
      leading to cellular dysfunction.
AB  - 1. Recent studies have revealed an association between coronary risk factors and
      both the number and function of bone marrow-derived endothelial progenitor cells
      (EPC). We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on
      the senescence of EPC, leading to cellular dysfunction. 2. Endothelial progenitor
      cells were isolated from human peripheral blood and characterized. The exposure
      of cultured EPC to ox-LDL (10 microg/mL) significantly accelerated the rate of
      senescence compared with control during 20 days in culture as determined by
      acidic beta-galactosidase staining. Oxidized LDL-induced EPC senescence was
      significantly inhibited by pretreatment with either lectin-like ox-LDL receptor-1
      (LOX-1) antibody (Ab) or atorvastatin (P < 0.01). 3. Because cellular senescence
      is critically influenced by telomerase, which elongates telomeres, we measured
      telomerase activity using a polymerase chain reaction-ELISA-based assay. Oxidized
      LDL significantly diminished telomerase activity to approximately 50%, an effect
      that was significantly abolished by pretreatment with either LOX-1 Ab or
      atorvastatin (P < 0.01). 4. We examined whether ox-LDL-induced EPC senescence
      translates into EPC dysfunction. An MTS assay disclosed an inhibitory effect of
      ox-LDL on EPC proliferation. In a Matrigel assay, EPC treated with ox-LDL were
      less likely to participate in network formation compared with controls. 5. In
      conclusions, ox-LDL accelerates the onset of EPC senescence, which may be related
      to telomerase inactivation. Oxidized LDL-induced EPC senescence leads to the
      impairment of proliferative capacity and network formation.

PMID- 15236626
TI  - Isoliquiritigenin inhibits the proliferation and induces the apoptosis of human
      non-small cell lung cancer a549 cells.
AB  - 1. Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone
      structure 4,2',4'-trihydroxychalcone. In the present study, we report, for the
      first time, ISL-induced inhibition of the proliferation of the human non-small
      cell lung cancer A549 cell line. 2. The results showed that ISL not only
      inhibited A549 cell proliferation, but also induced apoptosis and blocked cell
      cycle progression in the G1 phase. An ELISA assay demonstrated that ISL
      significantly increased the expression of p53 and p21/WAF1 protein, which caused
      cell cycle arrest. 3. An enhancement in Fas and its two ligands, namely membrane
      bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), may be responsible for
      the apoptotic effect induced by ISL. 4. Taken together, the results indicate that
      the p53 and Fas/FasL apoptotic system may participate in the antiproliferative
      activity of ISL in A549 cells.

PMID- 15236627
TI  - 5'-aminoimidazole-4-carboxyamide-ribonucleoside-activated glucose transport is
      not prevented by nitric oxide synthase inhibition in rat isolated skeletal
      muscle.
AB  - 1. The nucleoside intermediate 5'-aminoimidazole-4-carboxyamide-ribonucleoside
      (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and
      increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase
      (nNOS)mu in skeletal muscle fibres. There is evidence that both AMPK and nNOSmu
      may be involved in the regulation of contraction-stimulated glucose uptake. 2. We
      examined whether both AICAR- and contraction-stimulated glucose uptake were
      mediated by NOS in rat skeletal muscle. 3. Rat isolated epitrochlearis muscles
      were subjected in vitro to electrically stimulated contractions for 10 min and/or
      incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG
      monomethyl-L-arginine (L-NMMA; 100 micromol/L). 4. Muscle contraction
      significantly (P < 0.05) altered the metabolic profile of the muscle. In
      contrast, AICAR and L-NMMA had no effect on the metabolic profile of the muscle,
      except that AICAR increased muscle 5'-aminoimidazole-4-carboxyamide
      ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a
      small but significant (P < 0.05) reduction in basal 3-O-methylglucose transport,
      which was observed in all treatments. 5'-Aminoimidazole-4-carboxyamide
      ribonucleoside significantly increased (P < 0.05) glucose transport above basal,
      with NOS inhibition decreasing this slightly (increased by 209% above basal
      compared with 184% above basal with NOS inhibition). Contraction significantly
      increased glucose transport above basal, with NOS inhibition substantially
      reducing this (107% increase vs 31% increase). 5'-Aminoimidazole-4-carboxyamide
      ribonucleoside plus contraction in combination were not additive on glucose
      transport. 5. These results suggest that NO plays a role in basal glucose uptake
      and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide
      do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle
      glucose uptake.

PMID- 15236628
TI  - Regulation of ion transport by 5-hydroxytryptamine in rat colon.
AB  - 1. 5-Hydroxytryptamine (5-HT) modulates the motility and secretion of the
      gastrointestinal tract. To examine the direct effect of 5-HT on the secretions of
      colonic epithelial cells, a short-circuit current was used to measure electrolyte
      transport in the rat stripped distal colon. A neuronal Na+ channel blocker and a
      cyclo-oxygenase inhibitor were routinely added in experiments to abolish the
      effects of the enteric nervous system and endogenous prostaglandin, respectively.
      2. Basolateral application of 5-HT (10 micromol/L) induced an increase in the
      short circuit current (ISC). Removal of extracellular Cl-, HCO3- or both resulted
      in a 59.6, 76.4 and 90% reduction of 5-HT-elicited responses, respectively. The
      Ca(2+)-dependent Cl- channel blocker 4,4'-diisothiocyanatostilbene-2,2'
      disulphonic acid (DIDS) had no effect on the 5-HT-induced increase in ISC, but
      the selective cystic fibrosis transmembrane conductance regulator (CFTR) channel
      blocker glibenclamide (1 mmol/L) inhibited 5-HT-induced increases in ISC by
      approximately 92.9%. Removal of apical Na+ reduced the 5-HT-induced increase in
      ISC by 33.3%. 3. Basolateral pretreatment with 100 micromol/L bumetanide (an
      inhibitor of the Na(+)-K(+)-2Cl- cotransporter), 200 micromol/L DIDS (an
      inhibitor of the Na(+)-HCO3- transporter or the Cl-/HCO3- exchanger) or both
      decreased the DeltaISC induced by 5-HT by approximately 75.5, 59.0 and 86.3%,
      respectively. Removal of basolateral Na+ also reduced the current evoked by 5-HT.
      4. The selective 5-HT4 antagonist GR113808 (1 micromol/L) totally abolished the 5
      HT-induced increase in ISC, whereas 2-methyl-5-HT (100 micromol/L) induced a weak
      ISC response. 5. In conclusion, the present study has demonstrated that 5-HT can
      elicit Cl(-)- and HCO3- anion secretion and Na+ absorption by acting directly on
      colonic epithelial cells via 5-HT4 receptors.

PMID- 15236629
TI  - A randomized, double-blind, placebo-controlled trial of pseudoephedrine in
      coryza.
AB  - 1. The aim of the present study was to assess the efficacy of pseudoephedrine in
      coryza. 2. In a double-blind, randomized, placebo-controlled design, 48 adults
      with acute coryza received a single oral dose of 60 mg pseudoephedrine (Sudafed;
      Pfizer Consumer HealthCare Group, Caringbah, NSW, Australia) or matching placebo.
      Before and after dosing, nasal airway resistance (NAR), nasal volume, the minimum
      intranasal cross-sectional area (MCA) and the symptom of nasal congestion were
      measured. 3. Pseudoephedrine produced a significant decrease in NAR (P = 0.005;
      95% confidence interval (CI) 0.073, 0.383). Nasal volume increased, but this did
      not reach significance (P = 0.07; 95% CI -0.842, 0.034). There was no change in
      MCA and symptoms. 4. In conclusion, pseudoephedrine has a moderate effect in
      decreasing objective measures of nasal congestion in coryza.

PMID- 15236630
TI  - Comparative bioavailability of two cefadroxil products using serum and urine data
      in healthy human volunteers.
AB  - 1. The aim of the present study was to assess the bioequivalence of two
      cefadroxil products, namely Ultracef (a reference product) in the form of a 500
      mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA)
      and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk
      Pharmaceutical Manufacturing, Tabuk, Saudi Arabia). 2. The study was performed
      under US Food and Drug Administration (FDA) guidelines (http://www.fda.gov/cder)
      on 24 healthy male subjects. Both products were administered orally as a single
      dose (1 x 500 mg capsule) separated by a 1 week washout period. Following oral
      administration, blood and urine samples were obtained and analysed for cefadroxil
      concentrations using a sensitive and specific HPLC assay. 3. There were no
      statistically significant differences between the two products in either the mean
      concentration-time profiles or the cumulative urinary excretion of cefadroxil at
      various times. Similarly, no statistical significance was observed in the
      pharmacokinetic parameters reflecting rate and extent of drug absorption. The
      relative extent of drug absorption, assessed by calculating the area under the
      curve (AUC) ratio for Roxil/Ultracef for 10 h and for infinity was 0.94 with 90%
      confidence limits (CL) of 0.91-0.98. In agreement with serum data, the average
      ratio (Roxil/Ultracef) of the cumulative amount of cefadroxil excreted in urine
      10 h after the dose was found to be 0.97, with 90% CL of 0.88-1.05. The CL of the
      AUC and cumulative urinary excretion ratios are within the FDA accepted limits
      for bioequivalent products (0.80-1.25). 4. These findings show that serum and
      urine data of cefadroxil are in agreement and indicate that Roxil (the test
      product) and Ultracef (the reference product) are bioequivalent in terms of the
      rate and extent of drug absorption.

PMID- 15236632
TI  - Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in
      human prostate cancer cells.
AB  - 1. The effect of maprotiline, an antidepressant, on human prostate cells is
      unclear. In the present study, the effect of maprotiline on [Ca2+]i and growth in
      PC3 human prostate cancer cells was measured using the fluorescent dyes fura-2
      and tetrazolium, respectively. 2. Maprotiline caused a rapid, concentration
      dependent increase in [Ca2+]i (EC50 = 200 micromol/L). The maprotiline-induced
      [Ca2+]i increase was reduced by removal of extracellular Ca2+ or pretreatment
      with nicardipine. 3. The maprotiline-induced Mn2+ influx-associated fura-2
      fluorescence quench directly suggests that maprotiline caused Ca2+ influx. 4. In
      Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum
      Ca(2+)-ATPase, caused a monophasic [Ca2+]i increase, after which the effects of
      maprotiline of increasing [Ca2+]i were abolished. In addition, pretreatment with
      maprotiline reduced a major portion of the thapsigargin-induced increase in
      [Ca2+]i. 5. U73122, an inhibitor of phospholipase C, abolished the ATP (but not
      maprotiline)-induced increase in [Ca2+]i. 6. Overnight incubation with 1-10
      micromol/L maprotiline did not alter cell proliferation, although incubation with
      30-50 micromol/L maprotiline decreased cell proliferation. 7, These findings
      suggest that maprotiline rapidly increases [Ca2+]i in human prostate cancer cells
      by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release and
      that it may modulate cell proliferation in a concentration-dependent manner.

PMID- 15236631
TI  - Hypo-osmotic stress inhibits doxorubicin-induced apoptosis via a protein kinase A
      dependent mechanism in cardiomyocytes.
AB  - 1. The clinical use of doxorubicin is limited by the development of severe
      cardiomyopathies linked, at least in part, to an abnormal increase in the rate of
      apoptotic cell death. Because cell shrinkage is considered to be a crucial step
      at the onset of apoptosis, the aim of the present study was to investigate
      whether a brief hypo-osmotic stress, which leads to an increase in cell volume,
      could interfere with the induction of apoptosis by doxorubicin in adult
      cardiomyocytes. 2. Cell volume expansion results in intracellular accumulation of
      cAMP, so we secondarily tested whether the protective effect of hypo-osmotic
      stress could be related to the cAMP pathway. Accordingly, apoptosis was induced
      by doxorubicin (1 micromol/L) in cardiomyocytes freshly isolated from New Zealand
      adult rabbit hearts. 3. Exposure to doxorubicin in an iso-osmotic medium (290
      mOsmol/kg H2O) induced a rapid decrease in cell volume, as well as increases in
      annexin V labelling and caspase-3 activity, two biological markers of apoptosis.
      These effects of doxorubicin were abolished by 15 min pretreatment with hypo
      osmotic stress at 220 mOsmol/kgH2O (HS 220). 4. This cytoprotective effect of HS
      220 was still observed when doxorubicin was added to the medium 60 min later, but
      it was abolished when the pretreatment by HS 220 was associated with the protein
      kinase A inhibitor KT 5720 (200 nmol/L). 5. Conversely, 15 min pretreatment with
      either the cAMP analogue 8-bromo-cAMP (0.5 mmol/L) or the adenylate cyclase
      activator forskolin (10 micromol/L) inhibited apoptosis induced by doxorubicin.
      6. In conclusion, these results demonstrate that: (i) apoptosis induced by
      doxorubicin can be counteracted by a hypo-osmotic stress in adult cardiomyocytes;
      and (ii) activation of the protein kinase A-dependent pathway plays a major role
      in the mechanism leading to the cytoprotective effect induced by a hypo-osmotic
      stress.

PMID- 15236633
TI  - Greater hypertrophy in right than left ventricles is associated with pulmonary
      vasculopathy in sinoaortic-denervated Wistar-Kyoto rats.
AB  - 1. Biventricular hypertrophy has been described in a high blood pressure
      variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic
      hypertension. To explore the possible involvement of the lung in SAD-induced
      right ventricular hypertrophy (RVH), we examined lung morphology, in addition to
      systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks
      after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a
      substantial elevation in BPV, with no change in the average level of arterial
      pressure. Biventricular hypertrophy following SAD was characterized by a greater
      hypertrophy in right than left ventricles; both absolute and normalized right
      ventricular weights were significantly increased by 22 and 27%, respectively, and
      only normalized left ventricular weight was significantly increased by 12%. No
      infarcts were found in any ventricles examined. 3. In the lung, the most
      prominent change following SAD was pulmonary vasculopathy, including wall
      thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries
      with an internal diameter of 70-130 microm, the external diameter, wall thickness
      and wall thickness to internal diameter ratio were increased in SAD compared with
      control rats. 4. There was no correlation between right and left ventricular
      weights. In contrast with BPV-correlated left ventricular weight, right
      ventricular weight was correlated with the wall thickness of the pulmonary
      artery, but not with BPV. 5. These findings suggest that greater RVH following
      SAD is associated with pulmonary vasculopathy, but is not secondary to the left
      ventricular problems or high BPV.

PMID- 15236634
TI  - Effect of glycine on tissue fatty acid composition in an experimental model of
      alcohol-induced hepatotoxicity.
AB  - 1. The aim of the present study was to investigate the effect of the
      administration of glycine, a non-essential amino acid, on blood alcohol levels
      and tissue fatty acid composition in experimental rats. 2. Liver cell damage was
      induced by the administration of ethanol (7.9 g/kg bodyweight) for 30 days by
      intragastric intubation. Control rats were given isocaloric glucose solution.
      Glycine was subsequently administered at a dose of 0.6 g/kg bodyweight every day
      by intragastric intubation for the next 30 days. 3. Feeding alcohol significantly
      elevated the activities of serum aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatases (ALP) and gamma-glutamyl transpeptidase
      (GGT) and altered the liver and brain fatty acid composition compared with
      control rats. Subsequently, glycine supplementation to alcohol-fed rats
      significantly lowered the activities of serum AST, ALT, ALP, GGT and normalized
      the liver and brain fatty acid composition compared with untreated alcohol-fed
      rats. 4. Thus, the present study demonstrates that oral administration of glycine
      confers a significant protective effect against alcohol-induced hepatotoxicity by
      virtue of its ability to optimize the activities of serum AST, ALT, ALP and GGT,
      as well as the tissue fatty acid composition.

PMID- 15236635
TI  - Dose-response of ropivacaine administered caudally to children undergoing
      surgical procedures under sedation with midazolam.
AB  - 1. In a double-blind randomized controlled design, 50 children were allocated to
      receive bupivacaine 0.25% or ropivacaine 0.25%, 0.32%, 0.40% or 0.50% by caudal
      block. 2. Caudal block was performed after induction of anaesthesia with 2-5%
      sevoflurane, atropine 10 microg/kg and midazolam 100-300 microg/kg. During the
      surgical procedure, patients were maintained under spontaneous ventilation and no
      intravenous or inhalatory anaesthetic agent was administered. For transoperative
      sedation, midazolam 100-300 microg/kg was administered every 0.5-1.0 h.
      Transoperative cardiovascular response, postoperative analgesia and local and
      systemic complications were evaluated. 3. Groups were similar (P > 0.05) in sex,
      age, weight and in the time elapsed from caudal block to the beginning of the
      surgical procedure. The surgical time was significantly lower in the ropivacaine
      0.25% group. The duration of analgesia was 24 h with ropivacaine 0.25% and
      approximately 10 h in the other four groups (P < 0.001). Linear regression
      analysis revealed a significant relationship between the postoperative analgesic
      period produced by ropivacaine and the surgical time (r = -0.48, two-sided P =
      0.002). Systolic and diastolic blood pressures remained in the physiologically
      normal range for the duration of the transoperative period. Vomiting was present
      in only one patient receiving ropivacaine 0.50%. 4. In children, the duration of
      analgesia produced by caudal block with ropivacaine may be affected by surgical
      time. At surgical times of 0.5-1 h, ropivacaine 0.25% produced at least 24 h
      postoperative analgesia. At similar surgical times, ropivacaine 0.32%, 0.40% and
      0.50% produced similar analgesic times to bupivacaine 0.25%.

PMID- 15236636
TI  - Comparison of angiotensin II-induced blood pressure and structural changes in
      Fischer 344 and Wistar Kyoto rats.
AB  - 1. The purpose of the present study was to evaluate the blood pressure (BP)
      response, the BP and heart rate (HR) components of the startle reaction and the
      structure of the carotid artery and the aorta during chronic infusion of
      angiotensin (Ang) II in Fischer 344 (F344) compared with Wistar Kyoto (WKY) rats,
      two in-bred normotensive contrasted strains. 2. Osmotic mini-pumps filled with
      saline vehicle or AngII (120 ng/kg per min) were implanted subcutaneously in 8
      week-old normotensive rats and infused for 4 weeks in F344 rats (saline, n = 10;
      AngII, n = 10) and WKY rats (saline, n = 10; AngII, n = 9). Basal BP, HR and the
      responses to an acoustic startle stimulus (duration 0.7 s, 115 dB) were recorded
      in conscious rats. The structure of the carotid artery and aorta was determined
      in 4% formaldehyde-fixed arteries. 3. Compared with WKY rats, vehicle-treated
      F344 rats had lower bodyweight (BW; 266 +/- 7 vs 299 +/- 9 g; P < 0.05) and heart
      weight (0.80 +/- 0.02 vs 0.98 +/- 0.04 g; P < 0.05) and higher aortic systolic BP
      (SBP; 131 +/- 1 vs 123 +/- 5 mmHg; P < 0.001) and diastolic BP (98 +/- 3 vs 89 +/
      2 mmHg; P < 0.001). In F344 rats, compared with the WKY rats, the wall
      thickness/BW ratio was increased in the carotid artery (156 +/- 9 vs 131 +/- 6
      nm/g; P < 0.05) and abdominal aorta (264 +/- 13 vs 217 +/- 12 nm/g; P < 0.05) and
      decreased in the thoracic aorta (246 +/- 13 vs 275 +/- 8 nm/g; P < 0.05). There
      was no difference in elastin and collagen density. Angiotensin II differentially
      enhanced BP in both strains: (SBP: 163 +/- 5 and 132 +/- 4 mmHg in F344 and WKY
      rats, respectively; P(strain x treatment) < 0.05). Circumferential wall stress
      was increased in the aorta of F344 rats compared with WKY rats (1176 +/- 39 vs
      956 +/- 12 kPa (P < 0.001) and 1107 +/- 42 vs 813 +/- 12 kPa (P < 0.001) in
      thoracic and abdominal aortas, respectively). The startle response was amplified
      in F344 rats, with enhanced increases in SBP and pulse pressure (PP) and
      bradycardia compared with responses of WKY rats (+44 +/- 9 mmHg, +10 +/- 2 mmHg
      and -40 +/- 17 b.p.m., respectively, in F344 rats vs+28 +/- 4 mmHg, + 4 +/- 2
      mmHg and -19 +/- 10 b.p.m. in WKY rats, respectively; P(strain) < 0.05 for BP and
      PP). The startle response was not affected by AngII. 4. These results indicate a
      higher BP producing an increase in wall thickness in F344 rats compared with WKY
      rats. We propose that an increase in sympathetic nervous activity causes these
      haemodynamic differences, as suggested by the excessive increase in BP during an
      acoustic startle stimulus. Angiotensin II increased BP in F344 rats, but did not
      exaggerate the increase in BP during the startle reaction.

PMID- 15236637
TI  - Technical knockout: understanding poxvirus pathogenesis by selectively deleting
      viral immunomodulatory genes.
AB  - The study of viral pathogens with genomes as large and complex as poxviruses
      represents a constant experimental challenge. Advances in recombinant DNA
      technologies have provided sophisticated methods to produce mutants defective in
      one or more viral genes, termed knockout (KO) viruses, thereby facilitating
      research into the impact of specific gene products on viral pathogenesis. Such
      strategies have rapidly advanced the systematic mining of many poxvirus genomes
      and enabled researchers to identify and characterize poxvirus genes whose
      functions represent the culmination of host and pathogen coevolution. Of
      particular interest are the multiple classes of virus-encoded immunomodulatory
      proteins that have evolved specifically to allow poxviruses to evade, obstruct or
      subvert critical elements within the host innate and acquired immune responses.
      Functional characterization of these viral genes by generating KO viruses and
      investigating the phenotypic changes that result is an important tool for
      understanding the molecular mechanisms underlying poxvirus replication and
      pathogenesis. Moreover, the insights gained have led to new developments in basic
      and clinical virology, provided a basis for the design of new vaccines and
      antivirals, and increased the potential application of poxviruses as
      investigative tools and sources of biotherapeutics for the treatment of human
      diseases.

PMID- 15236638
TI  - Immune escape and exploitation strategies of cytomegaloviruses: impact on and
      imitation of the major histocompatibility system.
AB  - Cytomegalovirus (CMV) has yielded many insights into immune escape mechanisms.
      Both human and mouse CMV encode a diverse array of gene products, many of which
      appear to modulate the immune response in the host. Some deflect the host
      response to infection and contribute to lifelong viral persistence while others
      exploit immune cells that respond to infection. Here, the viral functions that
      modulate and mimic host major histocompatibility complex (MHC) function will be
      reviewed. Viral gene products related to both classical and non-classical
      components of the MHC system assure the virus will persist in immunocompetent
      individuals. Examples of host countermeasures that neutralize viral
      immunomodulatory functions have emerged in the characterization of viral
      functions that contribute to this stand-off in CMVs that infect humans, other
      primates and rodents. CMV-induced disease occurs when the immune system is not
      yet developed, such as in the developing fetus, or when it is compromised, such
      as in allograft transplant recipients, suggesting that the balance between virus
      escape and host control is central to pathogenesis. Although evidence supports
      the dominant role of immune escape in CMV pathogenesis and persistence, MHC
      related immunomodulatory functions have been ascribed only subtle impact on
      pathogenesis and the immune response during natural infection. Viral gene
      products that interface with the MHC system may impact natural killer cell
      function, antigen presentation, and T lymphocyte immune surveillance. Many also
      interact with other cells, particularly those in the myeloid lineage, with
      consequences that have not been explored. Overall, the virus-encoded modulatory
      functions that have been acquired by CMV likely ensure survival and adaptation to
      the wide range of mammalian host species in which they are found.

PMID- 15236639
TI  - A cyclic AMP protein kinase A-dependent mechanism by which rotavirus impairs the
      expression and enzyme activity of brush border-associated sucrase-isomaltase in
      differentiated intestinal Caco-2 cells.
AB  - We undertook a study of the mechanism by which rhesus monkey rotavirus (RRV)
      impairs the expression and enzyme activity of brush border-associated sucrase
      isomaltase (SI) in cultured, human, fully differentiated, intestinal Caco-2
      cells. We provide evidence that the RRV-induced defects in the expression and
      enzyme activity of SI are not related to the previously observed, RRV-induced,
      Ca2+ -dependent, disassembly of the F-actin cytoskeleton. This conclusion is
      based on the facts that: (i) the intracellular Ca2+ blocker, BAPTA/AM, which
      antagonizes the RRV-induced increase in [Ca2+](i), fails to inhibit the RRV
      induced decrease in SI expression and enzyme activity; and (ii) Jasplakinolide
      (JAS) treatment, known to stabilize actin filaments, had no effect on the RRV
      induced decrease in SI expression. Results reported here demonstrate that the RRV
      induced impairment in the expression and enzyme activity of brush border
      associated SI results from a hitherto unknown mechanism involving PKA signalling.
      This conclusion is based on the observations that (i) intracellular cAMP was
      increased in RRV-infected cells and (ii) treatment of RRV-infected cells with PKA
      blockers resulted in the reappearance of apical SI expression, accompanied by the
      restoration of the enzyme activity at the brush border. In addition, in RRV
      infected cells a twofold increase of phosphorylated form of cytokeratin 18 was
      observed after immunopurification and Western Blot analysis, which was
      antagonized by exposing the RRV-infected cells to the PKA blockers.

PMID- 15236640
TI  - L-proline is essential for the intracellular differentiation of Trypanosoma
      cruzi.
AB  - Using as the host cell, a proline-requiring mutant of Chinese hamster ovary cell
      (CHO-K1), it was possible to arrest the differentiation of amastigote forms of
      Trypanosoma cruzi at the intermediate intracellular epimastigote-like stage.
      Complete differentiation to the trypomastigote stage was obtained by addition of
      L-proline to the medium. This effect was more pronounced using the T. cruzi CL-14
      clone that differentiates fully at 33 degrees C (permissive temperature) and
      poorly at 37 degrees C (restrictive temperature). A synchronous differentiation
      of T. cruzi inside the host-cell is then possible by temperature switching in the
      presence of proline. It was found that differentiation of intracellular
      epimastigotes and trypomastigote bursting were proline concentration dependent.
      The intracellular concentration of proline was measured as well as the transport
      capacity of proline by each stage of the parasite. Amastigotes have the highest
      concentration of free proline (8.09 +/- 1.46 mM) when compared to trypomastigotes
      (3.81 +/- 1.55) or intracellular epimastigote-like forms (0.45 +/- 0.06 mM). In
      spite of having the lowest content of intracellular free proline, intracellular
      epimastigotes maintained the highest levels of L-proline transport compared to
      trypomastigotes and intracellular amastigotes, providing evidence for a high
      turnover for the L-proline pool in that parasite stage. This is the first report
      to establish a relationship between proline concentration and intracellular
      differentiation of Trypanosoma cruzi in the mammalian host.

PMID- 15236641
TI  - Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins.
AB  - Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular
      bacterium Anaplasma phagocytophilum. The bacterium infects, survives, propagates
      in, and alters neutrophil phenotype, indicating unique survival mechanisms. AnkA
      is the only known A. phagocytophilum component that gains access beyond
      neutrophil vacuoles and is transported to the infected host cell nucleus. The
      ability of native and recombinant AnkA to bind DNA and nuclear proteins from host
      HL-60 cells was assessed by the use of immunoprecipitation after cis
      diamminedichloroplatinum (cis-DDP) DNA-protein crosslinking, by probing
      uninfected HL-60 cell nuclear lysates for AnkA binding, and by recovery and
      sequence analysis of immunoprecipitated DNA. AnkA binds HL-60 cell DNA as well as
      nuclear proteins of approximately 86, 53 and 25 kDa, whereas recombinant A.
      phagocytophilum Msp2 or control proteins do not. DNA immunoprecipitation reveals
      AnkA binding to a variety of target genes in the human genome, including genes
      that encode proteins with ATPase, tyrosine phosphatase and NADH dehydrogenase
      like functions. These data indicate that AnkA could exert some effect on cells
      through binding to protein:DNA complexes in neutrophil nuclei. Whether AnkA
      binding leads to neutrophil functional alterations, and how such alterations
      might occur will depend upon definitive identification of binding partners and
      associated metabolic and biochemical pathways.

PMID- 15236642
TI  - Regulated expression of pathogen-associated molecular pattern molecules in
      Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity
      and production of phenol-soluble modulins.
AB  - Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial
      pathogen Staphylococcus epidermidis that has a strong capacity to activate the
      human innate immune response. We developed a novel method based on liquid
      chromatography-mass spectrometry (LC-MS) to quantify the production of the
      individual PSM components. Each PSM peptide was abundant in most of the 76 S
      epidermidis strains tested. Importantly, none of the PSM components were secreted
      by an agr mutant strain, indicating that PSM synthesis is regulated strictly by
      the agr quorum-sensing system. Furthermore, the agr mutant strain failed to
      elicit production of TNFalpha by human myeloid cells and induced significantly
      less neutrophil chemotaxis compared with the wild-type strain. Thus, quorum
      sensing in S. epidermidis dramatically influenced activation of human host
      defence. We propose that an agr quorum-sensing mechanism facilitates growth and
      survival in infected hosts by adapting production of the pro-inflammatory PSMs to
      the stage of infection.

PMID- 15236643
TI  - A Rickettsia WASP-like protein activates the Arp2/3 complex and mediates actin
      based motility.
AB  - Spotted fever group Rickettsia are obligate intracellular pathogens that exploit
      the host cell actin cytoskeleton to promote motility and cell-to-cell spread.
      Although other pathogens such as Listeria monocytogenes use an Arp2/3 complex
      dependent nucleation mechanism to generate comet tails consisting of Y-branched
      filament arrays, Rickettsia polymerize tails consisting of unbranched filaments
      by a previously unknown mechanism. We identified genes in several Rickettsia
      species encoding proteins (termed RickA) with similarity to the WASP family of
      Arp2/3-complex activators. Rickettsia rickettsii RickA activated both the
      nucleation and Y-branching activities of the Arp2/3 complex like other WASP
      family proteins, and was sufficient to direct the motility of microscopic beads
      in cell extracts. Actin tails generated by RickA-coated beads consisted of Y
      branched filament networks. These data suggest that Rickettsia use an Arp2/3
      complex-dependent actin-nucleation mechanism similar to that of other pathogens.
      We propose that additional Rickettsia or host factors reorganize the Y-branched
      networks into parallel arrays in a manner similar to a recently proposed model of
      filopodia formation.

PMID- 15236644
TI  - Trans-genera reconstitution and complementation of an adhesion complex in
      Toxoplasma gondii.
AB  - Eimeria tenella and Toxoplasma gondii are obligate intracellular parasites
      belonging to the phylum Apicomplexa. In T. gondii, the microneme protein TgMIC2
      contains two well-defined adhesive motifs and is thought to be a key participant
      in the attachment and invasion of host cells. However, several attempts by
      different laboratories to generate a knockout (KO) of TgMIC2 have failed,
      implying that TgMIC2 is an essential gene. As Eimeria and Toxoplasma utilize the
      same mechanisms of invasion and have highly conserved adhesive proteins, we
      hypothesized that the orthologous molecule in Eimeria, EtMIC1, could functionally
      substitute in Toxoplasma to allow a knockout of TgMIC2. TgMIC2 is partnered with
      a protein called TgM2AP, which corresponds to EtMIC2 in Eimeria. Because the
      activity of TgMIC2 is most likely tightly linked to its association with TgM2AP,
      it was thought that the activity of EtMIC1 might similarly require its partner
      EtMIC2. EtMIC1 and EtMIC2 were introduced into T. gondii, and the presence of
      EtMIC1 allowed the first knockout clone of TgMIC2 to be obtained. The TgMIC2 KO
      resulted in significantly decreased numbers of invaded parasites compared to the
      parental clone. In the absence of TgMIC2, TgM2AP was incorrectly processed and
      mistargeted to the parasitophorous vacuole instead of the micronemes. These
      findings indicate that the EtMIC1 can compensate for the essential requirement of
      TgMIC2, but it cannot fully functionally substitute for TgMIC2 in the invasion
      process or for supporting the correct maturation and targeting of TgM2AP.

PMID- 15236645
TI  - Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight
      junctions strands in the lateral membrane of intestinal epithelial cells.
AB  - Infection of intestinal epithelial cells with enteropathogenic Escherichia coli
      (EPEC) disrupts tight junction (TJ) architecture and barrier function. The aim of
      this study was to determine the impact of EPEC on TJ protein interactions and
      localization. Human intestinal epithelial cells (T84) were infected for 1, 3 or 6
      h with EPEC. To probe the TJ protein-protein interactions, co
      immunoprecipitations were performed. The associations between ZO-1, occludin and
      claudin-1 progressively decreased after infection. Corresponding morphological
      changes were analysed by immunofluorescence confocal microscopy. Tight junction
      proteins progressively lost their apically restricted localization. Freeze
      fracture electron microscopy revealed the appearance of aberrant strands
      throughout the lateral membrane that contained claudin-1 and occludin as
      determined by immunogold labelling. These structural alterations were accompanied
      by a loss of barrier function. Mutation of the gene encoding EspF, important in
      the disruption of TJs by EPEC, prevented the disruption of TJs. Tight junction
      structure normalized following eradication of EPEC with gentamicin and overnight
      recovery. This is the first demonstration that a microbial pathogen can cause
      aberrant TJ strands in the lateral membrane of host cells. We speculate that the
      disruption of integral and cytoplasmic TJ protein interactions following EPEC
      infection allows TJ strands to form or diffuse into the lateral plasma membrane.

PMID- 15236647
TI  - The ARIA/EAACI criteria for antihistamines: an assessment of the efficacy, safety
      and pharmacology of desloratadine.
AB  - BACKGROUND: The definition of allergic rhinitis and the classification of its
      severity and treatment have advanced in recent years following the publication of
      the Allergic Rhinitis and its Impact of Asthma (ARIA) document. The ARIA and the
      European Academy of Allergology and Clinical Immunology (ARIA/EAACI) have
      published a set of recommendations that outline the pharmacological and clinical
      criteria to be met by medications commonly used in the treatment of allergic
      rhinitis. METHODS: An international group of experts met to assess the profile of
      the antihistamine, desloratadine, under the ARIA/EAACI criteria. Data on
      desloratadine were collected from peer-reviewed clinical studies and review
      articles, which were corroborated and augmented by comprehensive public access
      documents from the European Medicines Evaluation Agency (EMEA). RESULTS AND
      CONCLUSION: Based on this systematic review, it was concluded that the efficacy,
      safety and pharmacology of desloratadine broadly meet the ARIA/EAACI criteria for
      antihistamines.

PMID- 15236648
TI  - galaxieEST: addressing EST identity through automated phylogenetic analysis.
AB  - BACKGROUND: Research involving expressed sequence tags (ESTs) is intricately
      coupled to the existence of large, well-annotated sequence repositories.
      Comparatively complete and satisfactory annotated public sequence libraries are,
      however, available only for a limited range of organisms, rendering the absence
      of sequences and gene structure information a tangible problem for those working
      with taxa lacking an EST or genome sequencing project. Paralogous genes belonging
      to the same gene family but distinguished by derived characteristics are
      particularly prone to misidentification and erroneous annotation; high but
      incomplete levels of sequence similarity are typically difficult to interpret and
      have formed the basis of many unsubstantiated assumptions of orthology. In these
      cases, a phylogenetic study of the query sequence together with the most similar
      sequences in the database may be of great value to the identification process. In
      order to facilitate this laborious procedure, a project to employ automated
      phylogenetic analysis in the identification of ESTs was initiated. RESULTS:
      galaxieEST is an open source Perl-CGI script package designed to complement
      traditional similarity-based identification of EST sequences through employment
      of automated phylogenetic analysis. It uses a series of BLAST runs as a sieve to
      retrieve nucleotide and protein sequences for inclusion in neighbour joining and
      parsimony analyses; the output includes the BLAST output, the results of the
      phylogenetic analyses, and the corresponding multiple alignments. galaxieEST is
      available as an on-line web service for identification of fungal ESTs and for
      download / local installation for use with any organism group at
      http://galaxie.cgb.ki.se/galaxieEST.html. CONCLUSIONS: By addressing sequence
      relatedness in addition to similarity, galaxieEST provides an integrative view on
      EST origin and identity, which may prove particularly useful in cases where
      similarity searches return one or more pertinent, but not full, matches and
      additional information on the query EST is needed.

PMID- 15236649
TI  - The placental problem: linking abnormal cytotrophoblast differentiation to the
      maternal symptoms of preeclampsia.
AB  - The placenta is a remarkable organ. In normal pregnancy its specialized cells
      (termed cytotrophoblasts) differentiate into various specialized subpopulations
      that play pivotal roles in governing fetal growth and development. One
      cytotrophoblast subset acquires tumor-like properties that allow the cells to
      invade the decidua and myometrium, a process that attaches the placenta to the
      uterus. The same subset also adopts a vascular phenotype that allows these fetal
      cells to breach and subsequently line uterine blood vessels, a process that
      channels maternal blood to the rest of the placenta. In the pregnancy
      complication preeclampsia, which is characterized by the sudden onset of maternal
      hypertension, proteinuria and edema, cytotrophoblast invasion is shallow and
      vascular transformation incomplete. These findings, together with very recent
      evidence from animal models, suggest that preeclampsia is associated with
      abnormal placental production of vasculogenic/angiogenic substances that reach
      the maternal circulation with the potential to produce at least a subset of the
      clinical signs of this syndrome. The current challenge is to build on this
      knowledge to design clinically useful tests for predicting, diagnosing and
      treating this dangerous disorder.

PMID- 15236650
TI  - Regulation of major histocompatibility complex class II gene expression in
      trophoblast cells.
AB  - Trophoblast cells are unique because they are one of the few mammalian cell types
      that do not express major histocompatibility complex (MHC) class II antigens,
      either constitutively or after exposure to IFN-gamma. The absence of MHC class II
      antigen expression on trophoblast cells has been postulated to be one of the
      essential mechanisms by which the semi-allogeneic fetus evades immune rejection
      reactions by the maternal immune system. Consistent with this hypothesis,
      trophoblast cells from the placentas of women suffering from chronic inflammation
      of unknown etiology and spontaneous recurrent miscarriages have been reported to
      aberrantly express MHC class II antigens. The lack of MHC class II antigen
      expression on trophoblast cells is due to silencing of expression of the class II
      transactivator (CIITA), a transacting factor that is essential for constitutive
      and IFN-gamma-inducible MHC class II gene transcription. Transfection of
      trophoblast cells with CIITA expression vectors activates both MHC class II and
      class Ia antigen expression, which confers on trophoblast cells both the ability
      to activate helper T cells, and sensitivity to lysis by cytotoxic T lymphocytes.
      Collectively, these studies strongly suggest that stringent silencing of CIITA
      (and therefore MHC class II) gene expression in trophoblast cells is critical for
      the prevention of immune rejection responses against the fetus by the maternal
      immune system. The focus of this review is to summarize studies examining the
      novel mechanisms by which CIITA is silenced in trophoblast cells. The elucidation
      of the silencing of CIITA in trophoblast cells may shed light on how the semi
      allogeneic fetus evades immune rejection by the maternal immune system during
      pregnancy.

PMID- 15236652
TI  - Chorionic gonadotropin and uterine dialogue in the primate.
AB  - Implantation is a complex spatio-temporal interaction between the growing embryo
      and the mother, where both players need to be highly synchronized to be able to
      establish an effective communication to ensure a successful pregnancy. Using our
      in vivo baboon model we have shown that Chorionic Gonadotropin (CG), as the major
      trophoblast derived signal, not only rescues the corpus luteum but also modulates
      the uterine environment in preparation for implantation. This response is
      characterized by an alteration in both the morphological and biochemical activity
      in the three major cell types: luminal and glandular epithelium and stromal
      fibroblasts. Furthermore, CG and factors from the ovary have a synergistic effect
      on the receptive endometrium. Novel local effects of CG which influence the
      immune system to permit the survival of the fetal allograft and prevent
      endometrial cell death are also discussed in this review. An alternate
      extracellular signal-regulated kinase (ERK) activation pathway observed in
      epithelial endometrial cells and the possibility of differential expression of
      the CG/LH-R isoforms during gestation, open many questions regarding the
      mechanism of action of CG and its signal transduction pathway within the primate
      endometrium.

PMID- 15236651
TI  - The prolactin and growth hormone families: pregnancy-specific hormones/cytokines
      at the maternal-fetal interface.
AB  - The prolactin (PRL) and growth hormone (GH) gene families represent species
      specific expansions of pregnancy-associated hormones/cytokines. In this review we
      examine the structure, expression patterns, and biological actions of the
      pregnancy-specific PRL and GH families.

PMID- 15236653
TI  - Conceptus signals for establishment and maintenance of pregnancy.
AB  - Establishment and maintenance of pregnancy results from signaling by the
      conceptus (embryo/fetus and associated extraembryonic membranes) and requires
      progesterone produced by the corpus luteum (CL). In most mammals, hormones
      produced by the trophoblast maintain progesterone production by acting directly
      or indirectly to maintain the CL. In domestic animals (ruminants and pigs),
      hormones from the trophoblast are antiluteolytic in that they act on the
      endometrium to prevent uterine release of luteolytic prostaglandin F2 alpha
      (PGF). In cyclic and pregnant sheep, progesterone negatively autoregulates
      expression of the progesterone receptor (PR) gene in the endometrial luminal (LE)
      and superficial glandular epithelium (GE). Available evidence in cyclic sheep
      indicates that loss of the PR is closely followed by increases in epithelial
      estrogen receptors (ER) and then oxytocin receptors (OTR), allowing oxytocin to
      induce uterine release of luteolytic PGF pulses. In pregnant sheep, the conceptus
      trophoblast produces interferon tau (IFN tau) that acts on the endometrium to
      inhibit transcription of the ER alpha gene directly and the OTR gene indirectly
      to abrogate development of the endometrial luteolytic mechanism. Subsequently,
      sequential, overlapping actions of progesterone, IFN tau, placental lactogen (PL)
      and growth hormone (GH) comprise a hormonal servomechanism that regulates
      endometrial gland morphogenesis and terminal differentiated function to maintain
      pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that
      alters the direction of PGF secretion from an endocrine to exocrine direction,
      thereby sequestering luteolytic PGF within the uterine lumen. Conceptus estrogen
      also increases expression of fibroblast growth factor 7 (FGF-7) in the
      endometrial LE that, in turn, stimulates proliferation and differentiated
      functions of the trophectoderm, which expresses the FGF-7 receptor. Strategic
      manipulation of these physiological mechanisms can offer therapeutic schemes to
      improve uterine capacity, conceptus survival and reproductive health.

PMID- 15236654
TI  - Trophoblast-uterine interactions at implantation.
AB  - Implantation of the embryo in the uterus is a critical and complex event and its
      failure is widely considered an impediment to improved success in assisted
      reproduction. Depending on whether placentation is invasive or superficial
      (epitheliochorial), the embryo may interact transiently or undergo a prolonged
      adhesive interaction with the uterine epithelium. Numerous candidate interactions
      have been identified, and there is good progress on identifying gene networks
      required for early placentation. However no molecular mechanisms for the
      epithelial phase are yet firmly established in any species. It is noteworthy that
      gene ablation in mice has so far failed to identify obligatory initial molecular
      events.

PMID- 15236656
TI  - Comparative aspects of trophoblast development and placentation.
AB  - Based on the number of tissues separating maternal from fetal blood, placentas
      are classified as epitheliochorial, endotheliochorial or hemochorial. We review
      the occurrence of these placental types in the various orders of eutherian
      mammals within the framework of the four superorders identified by the techniques
      of molecular phylogenetics. The superorder Afrotheria diversified in ancient
      Africa and its living representatives include elephants, sea cows, hyraxes,
      aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos,
      anteaters and sloths, diversified in South America. All placentas examined from
      members of these two oldest superorders are either endotheliochorial or
      hemochorial. The superorder Euarchontoglires includes two sister groups, Glires
      and Euarchonta. The former comprises rodents and lagomorphs, which typically have
      hemochorial placentas. The most primitive members of Euarchonta, the tree shrews,
      have endotheliochorial placentation. Flying lemurs and all higher primates have
      hemochorial placentas. However, the lemurs and lorises are exceptional among
      primates in having epitheliochorial placentation. Laurasiatheria, the last
      superorder to arise, includes several orders with epitheliochorial placentation.
      These comprise whales, camels, pigs, ruminants, horses and pangolins. In
      contrast, nearly all carnivores have endotheliochorial placentation, whilst bats
      have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria
      are a number of insectivores that have many conserved morphological characters;
      none of these has epitheliochorial placentation. Consideration of placental type
      in relation to the findings of molecular phylogenetics suggests that the likely
      path of evolution in Afrotheria was from endotheliochorial to hemochorial
      placentation. This is also a likely scenario for Xenarthra and the bats. We argue
      that a definitive epitheliochorial placenta is a secondary specialization and
      that it evolved twice, once in the Laurasiatheria and once in the lemurs and
      lorises.

PMID- 15236655
TI  - Trophoblast gene expression: transcription factors in the specification of early
      trophoblast.
AB  - Azone of trophoblast specification is established when the embryo is a morula,
      presumably reflecting a unique combination of transcription factors in that zone
      of cells and the influence of various environmental cues and growth factors on
      them. A key first step in this process of specification is the down-regulation of
      Oct4, a transcription factor that acts as a negative regulator of trophoblast
      specification and of genes normally up-regulated as the trophectoderm first
      forms. The transcription factors believed to have a positive association with
      trophectoderm specification have been inferred primarily in two ways: by their
      expression patterns in embryos, ES cells and TS cells and by the consequences of
      gene disruption on embryonic development. Many of these transcription factors
      also control the expression of genes characteristically expressed in trophoblast
      but not in the epiblast, primitive endoderm and their derivatives. ES and TS
      cells from the mouse and other species are beginning to provide insights into the
      changes in gene expression that accompany lineage specification and the
      subsequent post-specification events that lead to functional trophoblast
      derivatives.

PMID- 15236658
TI  - The human allergens of mesquite (Prosopis juliflora).
AB  - BACKGROUND: A computerized statistical analysis of allergy skin test results
      correlating patient reactivities initiated our interest in the cross-reactive
      allergens of mesquite tree pollen. In-vitro testing with mesquite-sensitized
      rabbits and a variety of deciduous tree pollens revealed so many cross
      reactivities that it became apparent there could be more allergens in mesquite
      than previously described in the world literature. Our purpose was to examine the
      allergens of mesquite tree pollen (Prosopis juliflora) which elicit an IgE
      response in allergic humans so that future research could determine if these
      human allergens cross-react with various tree pollens in the same manner as did
      the mesquite antiserum from sensitized rabbits. METHODS: Proteins from commercial
      mesquite tree pollen were separated by polyacrylamide gel electrophoresis in the
      presence of sodium-dodecyl-sulphate. These mesquite proteins were subjected to
      Western blotting using pooled sera from ten mesquite-sensitive patients and goat
      anti-human IgE. The allergens were detected using an Amplified Opti-4-CN kit,
      scanned, and then interpreted by Gel-Pro software. RESULTS: Thirteen human
      allergens of mesquite pollen were detected in this study. CONCLUSION: The number
      of allergens in this study of mesquite exceeded the number identified previously
      in the literature. With the increased exposure to mesquite through its use in
      "greening the desert", increased travel to desert areas and exposure to mesquite
      in cooking smoke, the possible clinical significance of these allergens and their
      suggested cross-reactivity with other tree pollens merit further study.

PMID- 15236659
TI  - Risk factors and in-hospital outcomes in stroke and myocardial infarction
      patients.
AB  - BACKGROUND: Acute stroke (AS) and acute myocardial infarction (AMI) share major
      risk factors such as age, gender, and high blood pressure. The main objective of
      this study was to compare vascular risk factor profiles with in-hospital outcomes
      in AS and AMI patients. METHODS: We evaluated 486 consecutive patients who were
      admitted to Bjelovar General Hospital with diagnoses of AS (ischaemic stroke or
      intracerebral haemorrhage; N = 380) or AMI (N = 106) during a one year period.
      The frequency of risk factors and in-patient mortality rates were assessed in
      both groups. For statistical analysis we used t-tests and chi2 tests. RESULTS: AS
      patients were significantly older than AMI patients: the mean age for AS patients
      was 68.9 +/- 9.1 years, and for AMI patients was 62.8 +/- 11.7 years (p < 0.001).
      AMI was significantly more common than AS in patients younger than 65 years; 51%
      of this group had AMI and 26% had AS (p < 0.001). Hypertension was a more common
      risk factor in AS patients (69% AS patients vs. 58% AMI patients; p = 0.042).
      Patients who died did not differ significantly in age between the groups. In
      patient mortality rates were significantly higher in AS than AMI cases (31% vs.
      12%, p < 0.001 for all patients; 37% vs.5%, p < 0.001 for men). Women
      hospitalized for AMI were more likely to die in hospital than men (28% vs. 5%; p
      = 0.002). CONCLUSIONS: We found that age at the time of presentation was a
      significant differentiating factor between patients with AS and AMI. The only
      exceptions were women, whose ages at the onset of AS and AMI were similar. In
      contrast, patients who died did not differ significantly in age. We observed
      significantly higher inpatient mortality for men (when adjusted for age) than for
      women with AS. The five-fold higher in-patient mortality rate in women than in
      men with AMI is most likely to have resulted from other factors related to
      treatment.

PMID- 15236660
TI  - The Bipolar Affective Disorder Dimension Scale (BADDS)--a dimensional scale for
      rating lifetime psychopathology in bipolar spectrum disorders.
AB  - BACKGROUND: Current operational diagnostic systems have substantial limitations
      for lifetime diagnostic classification of bipolar spectrum disorders. Issues
      include: (1) It is difficult to operationalize the integration of diverse
      episodes of psychopathology, (2) Hierarchies lead to loss of information, (3)
      Boundaries between diagnostic categories are often arbitrary, (4) Boundaries
      between categories usually require a major element of subjective interpretation,
      (5) Available diagnostic categories are relatively unhelpful in distinguishing
      severity, (6) "Not Otherwise Specified (NOS)" categories are highly
      heterogeneous, (7) Subclinical cases are not accommodated usefully within the
      current diagnostic categories. This latter limitation is particularly pertinent
      in the context of the increasing evidence for the existence of a broader bipolar
      spectrum than has been acknowledged within existing classifications. METHOD: We
      have developed a numerical rating system, the Bipolar Affective Disorder
      Dimension Scale, BADDS, that can be used as an adjunct to conventional best
      estimate lifetime diagnostic procedures. The scale definitions were informed by
      (a) the current concepts of mood syndrome recognized within DSMIV and ICD10, (b)
      the literature regarding severity of episodes, and (c) our own clinical
      experience. We undertook an iterative process in which we initially agreed scale
      definitions, piloted their use on sets of cases and made modifications to improve
      utility and reliability. RESULTS: BADDS has four dimensions, each rated as an
      integer on a 0 - 100 scale, that measure four key domains of lifetime
      psychopathology: Mania (M), Depression (D), Psychosis (P) and Incongruence (I).
      In our experience it is easy to learn, straightforward to use, has excellent
      inter-rater reliability and retains the key information required to make
      diagnoses according to DSMIV and ICD10. CONCLUSIONS: Use of BADDS as an adjunct
      to conventional categorical diagnosis provides a richer description of lifetime
      psychopathology that (a) can accommodate sub-clinical features, (b) discriminate
      between illness severity amongst individuals within a single conventional
      diagnostic category, and (c) demonstrate the similarity between the illness
      experience of individuals who have been classified into different disease
      categories but whose illnesses both fall near the boundaries between the two
      categories. BADDS may be useful for researchers and clinicians who are interested
      in description and classification of lifetime psychopathology of individuals with
      disorders lying on the bipolar spectrum.

PMID- 15236661
TI  - Polypharmacy in psychiatric practice in the Canary Islands.
AB  - BACKGROUND: Polypharmacy with psychoactive drugs is an increasingly common and
      debatable contemporary practice in clinical psychiatry based more upon experience
      than evidence. The objective of this study was to evaluate the prevalence and
      conditioners of polypharmacy in psychiatric patients. METHOD: A cross-sectional
      survey was carried out using the Canary Islands Health Service Clinical Records
      Database. A representative sample (n = 2,647) of patients with mental disorders
      receiving psychotropic medication was studied. RESULTS: The mean number of
      psychoactive drugs prescribed was 1.63 +/- 0.93 (range 1-7). The rate of
      polypharmacy was 41.9%, with 27.8% of patients receiving two drugs, 9.1%
      receiving three, 3.2% receiving four, and 1.8% of the patients receiving five or
      more psychotropic drugs. Multiple regression analysis shows that variables sex
      and diagnosis have a predictive value with regard to the number of psychotropic
      drug used, being men and schizophrenic patients the most predisposed.
      Benzodiazepines were the more prevalent drugs in monotherapy, while
      anticonvulsants and antipsychotics were the more used in combination with other
      treatment. A questionable very high degree of same-class polypharmacy was
      evidenced, while multi-class, adjunctive and augmentation polypharmacy seem to be
      more appropriate. CONCLUSIONS: Almost half of the psychiatric patients are
      treated with several psychotropics. Polypharmacy is common and seems to be
      problematic, especially when same class of drugs are prescribed together. Some
      diagnoses, such as schizophrenia, are associated with an increase risk of
      Polypharmacy but there is a lack of evidence based indicators that allows for
      quality evaluation on this practice.

PMID- 15236662
TI  - Chronological changes of incidence and prognosis of children with asymptomatic
      congenital cytomegalovirus infection in Sapporo, Japan.
AB  - BACKGROUND: Chronological changes of the incidence of congenital cytomegalovirus
      (CMV) infection and the longitudinal prognosis in children with asymptomatic
      congenital infection were investigated. METHODS: Congenital CMV infection, as
      demonstrated by isolation of the virus within the first week of life, was
      diagnosed in infants born in Sapporo, Japan, during the 26-year period between
      1977 and 2002. RESULTS: Congenital infection was diagnosed in 37 (0.31%) of
      11,938 infants. Thirty-two infants were (86.5%) asymptomatic and 5 (13.5%) were
      symptomatic at birth. CONCLUSIONS: Although a decrease in the total incidence of
      congenital CMV infection has been seen in recent years, screening of congenital
      infection at birth seems to be necessary to detect late-onset neurodevelopmental
      sequelae.

PMID- 15236663
TI  - Lack of chart reminder effectiveness on family medicine resident JNC-VI and NCEP
      III guideline knowledge and attitudes.
AB  - BACKGROUND: The literature demonstrates that medical residents and practicing
      physicians have an attitudinal-behavioral discordance concerning their positive
      attitudes towards clinical practice guidelines (CPG), and the implementation of
      these guidelines into clinical practice patterns. METHODS: A pilot study was
      performed to determine if change in a previously identified CPG compliance factor
      (accessibility) would produce a significant increase in family medicine resident
      knowledge and attitude toward the guidelines. The primary study intervention
      involved placing a summary of the Sixth Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI)
      and the National Cholesterol Education Program Expert Panel on Detection,
      Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP III) CPGs in
      all patient (>18 yr.) charts for a period of three months. The JNC VI and NCEP
      III CPGs were also distributed to each Wayne State family medicine resident, and
      a copy of each CPG was placed in the preceptor's area of the involved clinics.
      Identical pre- and post- intervention questionnaires were administered to all
      residents concerning CPG knowledge and attitude. RESULTS: Post-intervention
      analysis failed to demonstrate a significant difference in CPG knowledge. A
      statistically significant post-intervention difference was found in only on
      attitude question. The barriers to CPG compliance were identified as 1) lack of
      CPG instruction; 2) lack of critical appraisal ability; 3) insufficient time; 4)
      lack of CPG accessibility; and 5) lack of faculty modeling. CONCLUSION: This
      study demonstrated no significant post intervention changes in CPG knowledge, and
      only one question that reflected attitude change. Wider resident access to
      dedicated clinic time, increased faculty modeling, and the implementation of an
      electronic record/reminder system that uses a team-based approach are compliance
      factors that should be considered for further investigation. The interpretation
      of CPG non-compliance will benefit from a causal matrix focused on physician
      knowledge, attitudes, and behavior. Recent findings in resident knowledge
      behavior discordance may direct the future investigation of physician CPG non
      compliance away from generalized barrier research, and toward the development of
      information that maximizes the sense of individual practitioner urgency and
      certainty.

PMID- 15236664
TI  - WHO systematic review of maternal mortality and morbidity: methodological issues
      and challenges.
AB  - BACKGROUND: Reducing maternal mortality and morbidity are among the key
      international development goals. A prerequisite for monitoring the progress
      towards attainment of these goals is accurate assessment of the levels of
      mortality and morbidity. In order to contribute to mapping the global burden of
      reproductive ill-health, we are conducting a systematic review of incidence and
      prevalence of maternal mortality and morbidity. METHODS: We followed the standard
      methodology for systematic reviews. We prepared a protocol and a form for data
      extraction that identify key characteristics on study and reporting quality. An
      extensive search was conducted for the years 1997-2002 including electronic and
      hand searching. RESULTS: We screened the titles and abstracts of about 65,000
      citations identified through 11 electronic databases as well as various other
      sources. Four thousand six hundred and twenty-six full-text reports were
      critically appraised and 2443 are included in the review so far. Approximately
      one third of the studies were conducted in Asia and Africa. The reporting quality
      was generally low with definitions for conditions and the diagnostic methods
      often not reported. CONCLUSIONS: There are unique challenges and issues regarding
      the search, critical appraisal and summarizing epidemiological data in this
      systematic review of prevalence/incidence studies. More methodological studies
      and discussion to advance the field will be useful. Considerable efforts
      including leadership, consensus building and resources are required to improve
      the standards of monitoring burden of disease.

PMID- 15236665
TI  - Differential gene expression by integrin beta 7+ and beta 7- memory T helper
      cells.
AB  - BACKGROUND: The cell adhesion molecule integrin alpha 4 beta 7 helps direct the
      migration of blood lymphocytes to the intestine and associated lymphoid tissues.
      We hypothesized that beta 7+ and beta 7- blood memory T helper cells differ in
      their expression of genes that play a role in the adhesion or migration of T
      cells. RESULTS: RNA was prepared from beta 7+ and beta 7- CD4+ CD45RA- blood T
      cells from nine normal human subjects and analyzed using oligonucleotide
      microarrays. Of 21357 genes represented on the arrays, 16 were more highly
      expressed in beta 7+ cells and 18 were more highly expressed in beta 7- cells
      (>/=1.5 fold difference and adjusted P < 0.05). Several of the differentially
      expressed transcripts encode proteins with established or putative roles in
      lymphocyte adhesion and chemotaxis, including the chemokine receptors CCR9 and
      CCR10, the integrin alpha 4 subunit, L-selectin, KLRB1 (CD161), NT5E (CD73),
      LGALS1 and LGALS2 (galectin-1 and -2), and RGS1. Flow cytometry was used to
      determine whether differences in levels of transcripts encoding cell surface
      proteins were associated with differential expression of those proteins. Using
      this approach, we found that surface expression of KLRB1, LAIR1, and NT5E
      proteins was higher on beta 7+ memory/effector T cells than on beta 7- cells.
      CONCLUSIONS: Memory/effector T cells that express integrin beta 7 have a distinct
      pattern of expression of a set of gene transcripts. Several of these molecules
      can affect cell adhesion or chemotaxis and are therefore likely to modulate the
      complex multistep process that regulates trafficking of CD4+ memory T cell
      subsets with different homing behaviors.

PMID- 15236666
TI  - Genomic organization and the tissue distribution of alternatively spliced
      isoforms of the mouse Spatial gene.
AB  - BACKGROUND: The stromal component of the thymic microenvironment is critical for
      T lymphocyte generation. Thymocyte differentiation involves a cascade of
      coordinated stromal genes controlling thymocyte survival, lineage commitment and
      selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial)
      gene encodes a putative transcription factor which may be involved in T-cell
      development. In the testis, the Spatial gene is also expressed by round
      spermatids during spermatogenesis. RESULTS: The Spatial gene maps to the B3-B4
      region of murine chromosome 10 corresponding to the human syntenic region
      10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is
      alternatively spliced to generate two short isoforms (Spatial-alpha and -gamma)
      and two other long isoforms (Spatial-delta and -epsilon) comprising 5 additional
      exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial
      beta, which differs from other isoforms by an additional alternative exon of 69
      bases. This new exon encodes an interesting proline-rich signature that could
      confer to the 34 kDa Spatial-beta protein a particular function. By quantitative
      TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the
      thymus while the long isoforms are highly expressed in the testis. We further
      examined the inter-species conservation of Spatial between several mammals and
      identified that the protein which is rich in proline and positive amino acids, is
      highly conserved. CONCLUSIONS: The Spatial gene generates at least five
      alternative spliced variants: three short isoforms (Spatial-alpha, -beta and 
      gamma) highly expressed in the thymus and two long isoforms (Spatial-delta and 
      epsilon) highly expressed in the testis. These alternative spliced variants could
      have a tissue specific function.

PMID- 15236667
TI  - A chloroplast-localized vesicular transport system: a bio-informatics approach.
AB  - BACKGROUND: The thylakoid membrane of higher plant chloroplasts is made of
      membrane lipids synthesized in the chloroplast envelope. As the inner envelope
      membrane and the thylakoid are separated by the aqueous stroma, a system for
      transporting newly synthesized lipids from the inner envelope membrane to the
      thylakoid is required. Ultrastructural as well as biochemical studies have
      indicated that lipid transport inside the chloroplast could be mediated by a
      system similar in characteristics to vesicular trafficking in the cytosol. If
      indeed the chloroplast system is related to cytosolic vesicular trafficking
      systems, a certain degree of sequence conservation between components of the
      chloroplast and the cytosolic systems could be expected. We used the Arabidopsis
      thaliana genome and web-based subcellular localization prediction tools to search
      for chloroplast-localized homologues of cytosolic vesicular trafficking
      components. RESULTS: Out of the 28952 hypothetical proteins in the A. thaliana
      genome sequence, 1947 were predicted to be chloroplast-localized by two different
      subcellular localization predictors. In this chloroplast protein dataset, strong
      homologues for the main coat proteins of COPII coated cytosolic vesicles were
      found. Homologues of the small GTPases ARF1 and Sar1 were also found in the
      chloroplast protein dataset. CONCLUSION: Our database search approach gives
      further support to that a system similar to cytosolic vesicular trafficking is
      operational inside the chloroplast. However, solid biochemical data is needed to
      support the chloroplast localization of the identified proteins as well as their
      involvement in intra-chloroplast lipid trafficking.

PMID- 15236668
TI  - Conservation, diversification and expansion of C2H2 zinc finger proteins in the
      Arabidopsis thaliana genome.
AB  - BACKGROUND: The classical C2H2 zinc finger domain is involved in a wide range of
      functions and can bind to DNA, RNA and proteins. The comparison of zinc finger
      proteins in several eukaryotes has shown that there is a lot of lineage specific
      diversification and expansion. Although the number of characterized plant
      proteins that carry the classical C2H2 zinc finger motifs is growing, a
      systematic classification and analysis of a plant genome zinc finger gene set is
      lacking. RESULTS: We found through in silico analysis 176 zinc finger proteins in
      Arabidopsis thaliana that hence constitute the most abundant family of putative
      transcriptional regulators in this plant. Only a minority of 33 A. thaliana zinc
      finger proteins are conserved in other eukaryotes. In contrast, the majority of
      these proteins (81%) are plant specific. They are derived from extensive
      duplication events and form expanded families. We assigned the proteins to
      different subgroups and families and focused specifically on the two largest and
      evolutionarily youngest families (A1 and C1) that are suggested to be primarily
      involved in transcriptional regulation. The newly defined family A1 (24 members)
      comprises proteins with tandemly arranged zinc finger domains. Family C1 (64
      members), earlier described as the EPF-family in Petunia, comprises proteins with
      one isolated or two to five dispersed fingers and a mostly invariant QALGGH motif
      in the zinc finger helices. Based on the amino acid pattern in these helices we
      could describe five different signature sequences prevalent in C1 zinc finger
      domains. We also found a number of non-finger domains that are conserved in these
      families. CONCLUSIONS: Our analysis of the few evolutionarily conserved zinc
      finger proteins of A. thaliana suggests that most of them could be involved in
      ancient biological processes like RNA metabolism and chromatin-remodeling. In
      contrast, the majority of the unique A. thaliana zinc finger proteins are known
      or suggested to be involved in transcriptional regulation. They exhibit
      remarkable differences in the features of their zinc finger sequences and zinc
      finger arrangements compared to animal zinc finger proteins. The different zinc
      finger helix signatures we found in family C1 may have important implications for
      the sequence specific DNA recognition and allow inferences about the evolution of
      the members in this family.

PMID- 15236669
TI  - Gdt2 regulates the transition of Dictyostelium cells from growth to
      differentiation.
AB  - BACKGROUND: Dictyostelium life cycle consists of two distinct phases - growth and
      development. The control of growth-differentiation transition in Dictyostelium is
      not completely understood, and only few genes involved in this process are known.
      RESULTS: We have isolated a REMI (restriction enzyme-mediated integration)
      mutant, which prematurely initiates multicellular development. When grown on a
      bacterial lawn, these cells aggregate before the bacteria are completely cleared.
      In bacterial suspension, mutant cells express the developmental marker discoidin
      Igamma even at low cell densities and high concentrations of bacteria. In the
      absence of nutrients, mutant cells aggregate more rapidly than wild type, but the
      rest of development is unaffected and normal fruiting bodies are formed. The
      disrupted gene shows substantial homology to the recently described gdt1 gene,
      and therefore was named gdt2. While GDT1 and GDT2 are similar in many ways, there
      are intriguing differences. GDT2 contains a well conserved protein kinase domain,
      unlike GDT1, whose kinase domain is probably non-functional. The gdt2 and gdt1
      mRNAs are regulated differently, with gdt2 but not gdt1 expressed throughout
      development. The phenotypes of gdt2- and gdt1- mutants are related but not
      identical. While both initiate development early, gdt2- cells grow at a normal
      rate, unlike gdt1- mutants. Protein kinase A levels and activity are essentially
      normal in growing gdt2- mutants, implying that GDT2 regulates a pathway that acts
      separately from PKA. Gdt1 and gdt2 are the first identified members of a family
      containing at least eight closely related genes. CONCLUSIONS: We have isolated
      and characterised a new gene, gdt2, which acts to restrain development until
      conditions are appropriate. We also described a family of related genes in the
      Dictyostelium genome. We hypothesise that different family members might control
      similar cellular processes, but respond to different environmental cues.

PMID- 15236670
TI  - Gene therapy for severe combined immune deficiency.
AB  - Infants born with severe combined immune deficiencies are prone to life
      threatening infections and, without treatment, do not survive beyond the first
      year of life. Haematopoietic stem cell transplantation from a fully matched donor
      offers the possibility of cure. In the absence of a suitable matched donor,
      haploidentical transplants from a parental donor may be undertaken, but these are
      associated with more complications and lower success rates. Recently, an
      alternative therapeutic option based on retroviral gene delivery has been used to
      correct X-linked severe combined immune deficiency (SCID-X1) and adenosine
      deaminase deficiency. Clinical trials have established that in situations where
      ex vivo gene transfer into haematopoietic progenitor cells confers a strong
      selective advantage, the procedure is a feasible alternative to haploidentical
      transplantation, with favourable kinetics of immune reconstitution.

PMID- 15236671
TI  - Recent developments in research into the Cyathostominae and Anoplocephala
      perfoliata.
AB  - Intestinal helminths are an important cause of equine disease. Of these
      parasites, the Cyathostominae are the commonest group that infect horses. These
      nematodes consist of a complex tribe of 51 species, although individual horses
      tend to harbour 10 or so common species, in addition to a few rarer species. The
      Cyathostominae can be extremely pathogenic, and high levels of infection result
      in clinical symptoms ranging from chronic weight loss to colic, diarrhoea and
      death. As part of their life cycle, immature cyathostomins penetrate the large
      intestinal wall, where they can enter a state of inhibited larval development.
      These larvae can exist in this state for months to years, after which they
      subsequently re-emerge. If larvae re-emerge in large numbers (i.e. several
      million), severe pathological consequences ensue. The inhibited larvae are also
      relatively refractory to several of the currently available anthelmintics, so
      that horses treated previously with anthelmintics can still carry life
      threatening burdens of these parasitic stages. Little is known about the
      cyathostomin larvae during their mucosal phase, and current research efforts are
      focused on investigating the biology of these stages. Much of the research
      described here highlights this area of research and details studies aimed at
      investigating the host immune responses that the mucosal larvae invoke. As part
      of this research effort, molecular tools have been developed to facilitate the
      identification of larval and egg stages of cyathostomins. These molecular tools
      are now proving very useful in the investigation of the relative contributions
      that individual, common cyathostomin species make to the pathology and
      epidemiology of mixed helminth infections. At the more applied level, research is
      also in progress to develop an immunodiagnostic test that will allow numbers of
      mucosal larvae to be estimated. This test utilises antigen-specific IgG(T) serum
      antibody responses as markers of infection. As anthelmintic resistance will be
      the major constraint on the future control of the Cyathostominae, researchers are
      now actively investigating this area and studies aimed at elucidating the
      molecular mechanisms of drug resistance are described. Another parasite which has
      assumed a clinically important role in horses is the tapeworm, Anoplocephala
      perfoliata. This parasite is prevalent world-wide and has been shown to be a
      significant cause of equine colic. Because previous methods of estimating the
      infection intensity of tapeworm were inaccurate, recent research has been
      directed at developing an immunodiagnostic ELISA for these cestodes. Specific
      IgG(T) responses to antigens secreted by adult tapeworms have been shown to
      provide a reasonable indication of infection intensity. An ELISA based on these
      responses is now commercially available. The steps involved in the development of
      this ELISA are described here. In addition to these recent advances in research,
      this review also outlines the principle areas for future research into these
      important equine parasites.

PMID- 15236672
TI  - Rhodococcus equi.
AB  - Rhodococcus equi is an important cause of subacute or chronic abscessating
      bronchopneumonia of foals up to 3-5 months of age. It shares the lipid-rich cell
      wall envelope characteristic of the mycolata, including Mycobacterium
      tuberculosis, as well as the ability of pathogenic members of this group to
      survive within macrophages. The possession of a large virulence plasmid in
      isolates recovered from pneumonic foals is crucial for virulence. The plasmid
      contains an 27 kb pathogenicity island (PI) that encodes seven related virulence
      associated proteins (Vaps), including the immunodominant surface-expressed
      protein, VapA. Only PI genes are differentially expressed when the organism is
      grown in macrophages in vitro. Ten of the PI genes, including six Vap genes, have
      signal sequences, suggesting that they are exported from the cell to interact
      with the macrophage. Different PI genes are regulated by temperature, pH, iron,
      oxidative stress and probably also by magnesium, all environmental changes
      encountered after environmental R. equi are inhaled in dust and are ingested into
      macrophages in the lung. The basis of pathogenicity of R. equi is its ability to
      multiply in and eventually to destroy alveolar macrophages. Infectivity is
      largely or exclusively limited to cells of the monocyte-macrophage lineage.
      Current evidence suggests that infection of foals with virulent R. equi results
      in some foals in subversion of cell-mediated immunity and development of an
      ineffective and sometimes lethal Th2-based immune response. Significant progress
      has been made recently in the development of R. equi-E. coli shuttle vectors,
      transformation and random and site specific mutagenesis procedures, all of which
      will be important in molecular dissection of the mechanisms by which R. equi
      subverts normal macrophage killing mechanisms and cell-mediated immunity.

PMID- 15236673
TI  - The pathogenic equine streptococci.
AB  - Streptococci pathogenic for the horse include S. equi (S. equi subsp. equi), S.
      zooepidemicus (S. equi subsp. zooepidemicus), S. dysgalactiae subsp. equisimilis
      and S. pneumoniae capsule Type III. S. equi is a clonal descendent or biovar of
      an ancestral S. zooepidemicus strain with which it shares greater than 98% DNA
      homology and therefore expresses many of the same proteins and virulence factors.
      Rapid progress has been made in identification of virulence factors and proteins
      uniquely expressed by S. equi. Most of these are expressed either on the
      bacterial surface or are secreted. Notable examples include the antiphagocytic
      SeM and the secreted pyrogenic superantigens SePE-I and H. The genomic DNA
      sequence of S. equi will greatly accelerate identification and characterization
      of additional virulence factors and vaccine targets. Although it is the most
      frequently isolated opportunist pyogen of the horse, S. zooepidemicus has been
      the subject of few contemporary research studies. Variation in the protectively
      immunogenic SzP proteins has, however, been well characterized. Given its
      opportunist behavior, studies are urgently needed on regulation of virulence
      factors such as capsule and proteases. Likewise, information is also very limited
      on virulence factors and associated gene regulation of S. dysgalactiae subspecies
      equisimilis. It has recently been shown that equine isolates of Streptococcus
      pneumoniae are clonal, a feature shared with S. equi. All equine isolates express
      capsule Type III, are genetically similar, and have deletions in the genes for
      autolysin and pneumolysin. In summary, the evolving picture of the interaction of
      the equine pathogenic streptococci and their host is that of multiple virulence
      factors active at different stages of pathogenesis. The inherent complexity of
      this interaction suggests that discovery of effective combinations of immunogens
      from potential targets identified in genomic sequence will be laborious.

PMID- 15236674
TI  - Current perspectives on control of equine influenza.
AB  - Influenza A viruses of the H3N8 subtype are a major cause of respiratory disease
      in horses. Subclinical infection with virus shedding can occur in vaccinated
      horses, particularly where there is a mismatch between the vaccine strains and
      the virus strains circulating in the field. Such infections contribute to the
      spread of the disease. Rapid diagnostic techniques are available for detection of
      virus antigen and can be used as an aid in control programmes. Improvements have
      been made to methods of standardising inactivated virus vaccines, and a direct
      relationship between vaccine potency measured by single radial diffusion and
      vaccine-induced antibody measured by single radial haemolysis has been
      demonstrated. Improved adjuvants and antigenic presentation systems extend the
      duration of immunity induced by inactivated virus vaccines, but high levels of
      antibody are required for protection against field infection. In addition to
      circulating antibody, infection with influenza virus stimulates mucosal and
      cellular immunity; unlike immunity to inactivated virus vaccines, infection
      induced immunity is not dependent on the presence of circulating antibody to HA.
      Live attenuated or vectored equine influenza vaccines, which may better mimic the
      immunity generated by influenza infection than inactivated virus vaccines, are
      now available. Mathematical modelling based upon experimental and field data has
      been applied to examine issues relating to vaccine efficacy at the population
      level. A vaccine strain selection system has been implemented and a more global
      approach to the surveillance of equine influenza is being developed.

PMID- 15236675
TI  - Equine viral vaccines: the past, present and future.
AB  - The increasing international movement of horses combined with the relaxation of
      veterinary regulations has resulted in an increased incidence of equine
      infectious diseases. Vaccination, along with management measures, has become the
      primary method for the effective control of these diseases. Traditionally
      modified live and inactivated vaccines have been used and these vaccines have
      proven to be very successful in preventing disease. However, there are a number
      of equine infectious diseases for which conventional technology has shown its
      limitations. The advent of recombinant technology has stimulated the development
      of second generation vaccines, including gene deleted mutants, live vectored
      vaccines and DNA vaccines. These vaccines have in common that protective antigens
      are endogenously processed and presented along the molecules of the MHC I and MHC
      II complex, resulting in the stimulation of both humoral and cell-mediated immune
      responses similar to natural infection. The present paper provides a review of
      the vaccines being employed today against the most important equine viral
      diseases followed by a summary of new developments that are expected to bring
      improved vaccines to the market in the foreseeable future.

PMID- 15236676
TI  - African horse sickness.
AB  - African horse sickness virus (AHSV) causes a non-contagious, infectious insect
      borne disease of equids and is endemic in many areas of sub-Saharan Africa and
      possibly Yemen in the Arabian Peninsula. However, periodically the virus makes
      excursions beyond its endemic areas and has at times extended as far as India and
      Pakistan in the east and Spain and Portugal in the west. The vectors are certain
      species of Culicoides biting midge the most important of which is the Afro
      Asiatic species C. imicola. This paper describes the effects that AHSV has on its
      equid hosts, aspects of its epidemiology, and present and future prospects for
      control. The distribution of AHSV seems to be governed by a number of factors
      including the efficiency of control measures, the presence or absence of a long
      term vertebrate reservoir and, most importantly, the prevalence and seasonal
      incidence of the major vector which is controlled by climate. However, with the
      advent of climate-change the major vector, C. imicola, has now significantly
      extended its range northwards to include much of Portugal, Spain, Italy and
      Greece and has even been recorded from southern Switzerland. Furthermore, in many
      of these new locations the insect is present and active throughout the entire
      year. With the related bluetongue virus, which utilises the same vector species
      of Culicoides this has, since 1998, precipitated the worst outbreaks of
      bluetongue disease ever recorded with the virus extending further north in Europe
      than ever before and apparently becoming endemic in that continent. The prospects
      for similar changes in the epidemiology and distribution of AHSV are discussed.

PMID- 15236677
TI  - West Nile virus infection of horses.
AB  - West Nile virus (WNV) is a flavivirus closely related to Japanese encephalitis
      and St. Louis encephalitis viruses that is primarily maintained in nature by
      transmission cycles between mosquitoes and birds. Occasionally, WNV infects and
      causes disease in other vertebrates, including humans and horses. West Nile virus
      has re-emerged as an important pathogen as several recent outbreaks of
      encephalomyelitis have been reported from different parts of Europe in addition
      to the large epidemic that has swept across North America. This review summarises
      the main features of WNV infection in the horse, with reference to complementary
      information from other species, highlighting the most recent scientific findings
      and identifying areas that require further research.

PMID- 15236678
TI  - Equine Infectious Anemia Virus (EIAV): what has HIV's country cousin got to tell
      us?
AB  - Equine Infectious Anemia Virus (EIAV) is a lentivirus, of the Retrovirus family,
      with an almost worldwide distribution, infecting equids. It causes a persistent
      infection characterized by recurring febrile episodes associating viremia, fever,
      thrombocytopenia, and wasting symptoms. The disease is experimentally
      reproducible by inoculation of Shetland ponies or horses with EIAV pathogenic
      strains. Among lentiviruses, EIAV is unique in that, despite a rapid virus
      replication and antigenic variation, most animals progress from a chronic stage
      characterized by recurring peaks of viremia and fever to an asymptomatic stage of
      infection. The inapparent carriers remain infective for life, as demonstrated by
      experimental transfer of blood to naive animals. The understanding of the
      correlates of this immune control is of great interest in defining vaccine
      strategies. Research on EIAV, this "country cousin" of HIV (Human
      Immunodeficiency Virus), over the last five decades has produced some interesting
      results on natural immunological control of lentivirus replication and disease
      and on the nature and role of virus variation in persistence and pathogenesis.
      These studies are of interest in the context of HIV and efforts to develop a
      vaccine. This review will focus on some of the most recent results.

PMID- 15236680
TI  - Monoliths for microfluidic devices in proteomics.
AB  - We report here on the preparation of monolithic capillary columns in view to
      their integration in a microsystem for on-chip sample preparation before their on
      line analysis by electrospray and mass spectrometry (ESI-MS). These monolithic
      columns are based on polymer materials and consist of reverse phases for peptide
      separation and/or desalting. They were prepared using lauryl methacrylate (LMA),
      ethylene dimethacrylate (EDMA) as well as a suitable porogenic mixture composed
      of cyclohexanol and ethylene glycol. The resulting stationary phases present thus
      a C12-functionality. The LMA-based columns were first prepared in a capillary
      format using capillary tubing of 75 microm i.d. and tested in nanoLC-MS
      experiments for the separation of a commercial Cytochrome C digest composed of 12
      peptidic fragments whose isoelectric point values and hydrophobic character cover
      a wide range. The LMA-based columns were capable of separating the peptidic
      fragments and their performances were seen to be similar as those of standard
      commercial columns dedicated to proteomic purposes with calculated separation
      efficiencies up to 145 x 10(3) plates/m. Monolithic LMA-based phases were then
      successfully polymerized in microchannels fabricated using the negative
      photoresist SU-8. After the polymerization, the systems were seen to withstand
      the pressures applied during the nanoLC-MS separation tests that were carried out
      in the same conditions as for the monolithic capillary columns. The pressure drop
      during these tests of the in-microchannel monoliths was as high as 50 bar;
      however, the separation was not as good as for a capillary format which could be
      accounted for by the monolith dimensions.

PMID- 15236681
TI  - Utilization of newly developed immobilized enzyme reactors for preparation and
      study of immunoglobulin G fragments.
AB  - The newly developed immobilized enzyme reactors (IMERs) with proteolytic enzymes
      chymotrypsin, trypsin or papain were used for specific fragmentation of high
      molecular-mass and heterogeneous glycoproteins immunoglobulin G (IgG) and
      crystallizable fragment of IgG (Fc). The efficiency of splitting or digestion
      were controlled by RP-HPLC. The specificity of digestion by trypsin reactor was
      controlled by MS. IMERs (trypsin immobilized on magnetic microparticles focused
      in a channel of magnetically active microfluidic device) was used for digestion
      of the whole IgG molecule. The sufficient conditions for IgG digestion in
      microfluidic device (flow rate, ratio S:E, pH, temperature) were optimized. It
      was confirmed that the combination of IMERs with microfluidic device enables
      efficient digestion of highly heterogeneous glycoproteins such as IgG in
      extremely short time and minimal reaction volume.

PMID- 15236682
TI  - 2-Mercapto-5-benzimidazolesulfonic acid: an effective multimodal ligand for the
      separation of antibodies.
AB  - The report describes the use of 2-mercapto-5-benzimidazolesulfonic acid (MBISA)
      as a ligand for the separation of antibodies by chromatography. The ligand shows
      a relatively specific adsorption property for antibodies from very crude
      biologicals at pH 5.0-5.5. At this pH range most of other proteins do not
      interact with the resin especially when the ionic strength is similar to
      physiological conditions. Several characterization studies are described such as
      antibody adsorption in different conditions of ionic strength, pH and
      temperature. These properties are advantageously used to selectively capture
      antibodies from very crude feed stocks without dilution or addition of lyotropic
      salts. Demonstration was made that the adsorption mechanism is neither based on
      ion exchange nor on hydrophobic associations, but rather as an assembly of a
      variety of properties of the ligand itself. Binding capacity in the described
      conditions ranges between 25 and 30 mg/mL of resin. The sorbent does not co
      adsorb albumin (Alb) and seems compatible with a large variety of feedstocks.
      Quantitative antibody desorption occurs when the pH is raised above 8.5. The
      final purity of the antibody depends on the nature of the feedstock, and can
      reach levels of purity as high as 98%. Even with very crude biological liquids
      such as ascites fluids, cell culture supernatants and Chon fraction II + III from
      human plasma fractionation where the number of protein impurities is particularly
      large, immunoglobumins G (IgG) were separated at high purity level in a single
      step.

PMID- 15236683
TI  - Insulin adsorption on coated silica based supports grafted with N
      acetylglucosamine by liquid affinity chromatography.
AB  - Silica beads are coated with dextran carrying a calculated amount of positively
      charged diethylassminoethyl groups (DEAE) in order to neutralize negative charged
      silanol groups at the silica surface and in this way to minimize non specific
      interactions between silica surface and proteins in solution. Dextran-coated
      silica supports are potentially excellent stationary phases for high-performance
      liquid chromatography of proteins. These supports combine the advantages of
      polysaccharide phases with the excellent mechanical characteristics of silica.
      These supports (silica-dextran-DEAE = SID) are easily functionalized by grafting
      N-acetylglucosamine (GlcNAc) using conventional coupling methods. The
      performances of the support bearing GlcNAc are studied by high-performance liquid
      affinity chromatography (HPLAC) of insulin, the hypoglycemic peptide hormone of
      the human organism. The study shows that these supports exhibit a reversible and
      specific affinity towards insulin and allow separations with high purification
      yields. Moreover, the influence of different physico-chemical parameters (pH,
      NaCl and insulin concentration) on insulin retention on the support was analysed.
      This allowed us to optimize the conditions of adsorption and to better understand
      the interaction mechanisms between insulin and GlcNAc as biospecific ligand.

PMID- 15236684
TI  - Affinity parameters of amino acid derivative binding to molecularly imprinted
      nanospheres consisting of poly[(ethylene glycol dimethacrylate)-co-(methacrylic
      acid)].
AB  - The binding of L-Boc-phenylalanine anilide (BFA) and L-Boc-phenylalanine (phe) to
      molecularly imprinted and non-imprinted polymer nanoparticles consisting of
      poly[(ethylene glycol dimethacrylate)-co-(methacrylic acid)] has been
      investigated by adsorption experiments and mathematical modeling. The
      experimental isotherms have been mathematically adapted following the models of
      Freundlich, Langmuir, Langmuir-Freundlich, Bi-Langmuir, and extended Langmuir.
      The extended Langmuir model differentiated between specific and nonspecific
      binding of the ligand to the receptor nanoparticles and rendered excellent
      fitting of the experimental data. It delivered a thermodynamic and kinetic
      parameter set on the experimental association curves of L-BFA by L-BFA-imprinted
      nanospheres in suspension experiments with the equilibrium constant KD= 4.09 +/-
      0.69 micromol L(-1) and the kinetic association rate constant Ka= 5.60 mL
      micromol(-1) min(-1).

PMID- 15236685
TI  - Mercaptoheterocyclic ligands grafted on a poly(ethylene vinyl alcohol) membrane
      for the purification of immunoglobulin G in a salt independent thiophilic
      chromatography.
AB  - In this study, we attempted a limited combinatorial approach for designing
      affinity ligands based on mercaptoheterocyclic components. The template, divinyl
      sulfone structure (DVS), which was grafted on poly(ethylene vinyl alcohol) (PEVA)
      hollow fiber membrane, has served for the tethering of different heterocyclic
      compounds as pyridine, imidazole, purine and pyrimidine rings. Their ability to
      adsorb specifically IgG in a salt independent manner out of pure IgG solution,
      mixture of IgG/albumin and human plasma was demonstrated. Mercapto methyl
      imidazole (MMI) has shown the best adsorption of IgG in terms of binding
      capacity. No subclass discrimination was observed on all tested ligands except
      for mercapto methyl pyrimidine where the major IgG subclass adsorbed was IgG3.
      MMI gave an IgG binding capacity of 100 microg/cm2 of hollow fiber membrane
      surface area.

PMID- 15236686
TI  - Immobilized metal-ion affinity chromatography of human antibodies and their
      proteolytic fragments.
AB  - Immobilized metal-ion affinity chromatography (IMAC) performed with four
      different transition metal ions: copper(II), nickel(II), zinc(II) and cobalt(II),
      was used to study the adsorption properties of human polyclonal gamma-globulines
      (IgG), Cohn II-III fractions, and their pepsin cleaved fragments: Fab'2 and F'c.
      In each case, digested products showed lower affinity for metal ions, as well by
      decreasing pH elution as by competition with imidazole. An explanation was
      proposed by the presence of a histidine (His) cluster in the F'c domain of IgGs,
      identified by computer calculation (accessible surface area (ASA) determination)
      as the more probable His 433-x-His 435 sequence presented in the CH3 domain of
      human IgG heavy chain. As shown by IMAC and electrophoresis, F'c and undigested
      IgG have higher affinity for transition metal ions than Fab'2 fragments and could
      be then separated in one step by IMAC. When chelated Zn(II) or Co(II) are used as
      ligands, the Fab'2 fragment could be easily recovered under mild conditions (pH
      7) in the non-retained fraction. This approach could be used as a powerful
      alternative to conventional protein A/G methods for the commercial preparation of
      non immunogen active Fab'2 fragments.

PMID- 15236687
TI  - Immobilization of a (dextran-adamantane-COOH) polymer onto beta-cyclodextrin
      modified silica.
AB  - Adamantane-modified compounds are known to form stable complexes with beta
      cyclodextrins (beta-CD) by host-guest interactions. In this study, the inclusion
      complex formed between beta-CD cavities and the adamantane group was evaluated
      for the elaboration of a cation-exchange support. The synthesis of the
      chromatographic supports involved three steps: (i) a polymer of beta-CD was
      grafted to diol-modified silica, (ii) a dextran polymer was modified by both
      adamantane groups and ionizable COOH functions, (iii) the dextran derivative (Ad
      Dex-COOH) was bound to the chromatographic support by complexation between the
      adamantane groups of the dextran and beta-CD cavities of the support. The polymer
      immobilization on the beta-CD support was successful as the resulting support
      exhibited weak cation-exchange properties. The stationary phase was easy to
      prepare under mild conditions (aqueous media, room temperature) and was quite
      stable when using aqueous mobile phases. The chromatographic behaviour of model
      proteins was studied in isocratic elution by examining the effect of salt
      concentration in the buffer on retention. A mixed retention mode was found for
      lysozyme, revealing both electrostatic and hydrophobic interactions with the
      stationary phase.

PMID- 15236688
TI  - Fungal mycelium--the source of chitosan for chromatography.
AB  - Mycelium of the mold Aspergillus niger was used as a raw material for the
      preparation of microbial chitosan. Aspergillus niger, the mold used for the
      production of citric acid, contains approx. 15% of chitin, which can be
      separated, transformed into chitosan, and used as a sorbent for chromatography.
      The main advantage of this material in comparison with krill chitosan is the
      uniformity of particle size leading to the low back-pressure in the column. The
      other advantage is the fact, that original fibrous structure of mycelial pellets
      could be stabilized before chitosan preparation by cross-linking with
      glutaraldehyde. The product prepared by this way -- crosslinked chitosan of
      uniform particle size, is highly porous, with high water regain and, as a result,
      low sedimentation velocity. Low sedimentation velocity is not disadvantage in
      chromatographic application, but may form some problems in batchwise operation.
      Chitosan as a polymer of glucosamine is anion exchanger in nature and the
      chromatographic properties of this anion exchanger was demonstrated by the
      chromatography of bovine blood plasma, glucose oxidase, and chicken pepsinogen.
      In all cases, the course of chromatography on crosslinked chitosan was compared
      with the chromatography on MONO Q (bovine blood plasma) or DEAE-cellulose
      (glucose oxidase, chicken pepsinogen) under the same protocol.

PMID- 15236689
TI  - Analysis of synthetic derivatives of peptide hormones by capillary zone
      electrophoresis and micellar electrokinetic chromatography with ultraviolet
      absorption and laser-induced fluorescence detection.
AB  - Capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography
      (MEKC) were used for the analysis of new synthetic derivatives of hypophysis
      neurohormones--vasopressin and oxytocin, and pancreatic hormone--human insulin
      (HI) and its octapeptide fragment, derivatized by fluorescent probe, 4-chloro-7
      nitrobenzo[1,2,5]oxadiazol (NBD). The suitable composition of background
      electrolytes (BGEs) was selected on the basis of calculated pH dependence of
      effective charge of analyzed peptides. Basic ionogenic peptides were analyzed by
      CZE in the acidic BGE composed of 100 mM H3PO4, 50 mM Tris, pH 2.25. The
      ionogenic peptides with fluorescent label, NBD, were analyzed in 0.5 M acetic
      acid, pH 2.5. The best MEKC separation of non-ionogenic peptides was achieved in
      alkaline BGE, 20 mM Tris, 5 mM H3PO4, with micellar pseudophase formed by 50 mM
      sodium dodecylsulfate (SDS), pH 8.8. Selected characteristics (noise,
      detectability of substance, sensitivity of detector) of the UV-absorption
      detectors (single wavelength detector, multiple-wavelength photodiode array
      detector (PDA), both of them operating at constant wavelength 206 nm) and laser
      induced fluorescence (LIF) detector (excitation/emission wavelength 488/520 nm)
      were determined. The detectability of peptides in the single wavelength detector
      was 1.3-6.0 micromol dm(-3) and in the PDA detector 1.6-3.1 micromol dm(-3). The
      LIF detection was more sensitive, the applied concentration of NBD derivative of
      insulin fragment in CZE analysis with LIF detection was three orders lower than
      in CZE with UV-absorption detector, and the detectability of this peptide was
      improved to 15.8 nmol dm(-3).

PMID- 15236690
TI  - Chromatographic purification of an insoluble histidine tag recombinant Ykt6p
      SNARE from Arabidopsis thaliana over-expressed in E. coli.
AB  - In order to undertake in plant cell the study of the endoplasmic reticulum (ER)
      Golgi apparatus (GA) protein and/or lipid vesicular transport pathway, expressed
      sequence tag (EST) coding for a homologue to the yeast soluble N-ethylmaleimide
      sensitive factor attachment protein receptors (SNAREs) Ykt6p has been cloned in
      Arabidopsis thaliana by reverse transcription polymerase chain reaction (RT-PCR).
      The corresponding protein was over-expressed as a recombinant histidine-tag (his
      tag) protein in E. coli. Starting from one litter of culture, an ultrasonic
      homogenization was performed for cell disruption and after centrifugation the
      Arabidopsis Ykt6p SNARE present in inclusion bodies in the pellet was
      solubilized. After centrifugation, the clarified feedstock obtained was injected
      onto an immobilized metal affinity chromatography (IMAC) in presence of 6 M
      guanidine and on-column refolding was performed. Folded and subsequently purified
      (94% purity) recombinant protein was obtained with 82% of recovery.

PMID- 15236691
TI  - Evaluation of three expanded bed adsorption anion exchange matrices with the aid
      of recombinant enhanced green fluorescent protein overexpressed in Escherichia
      coli.
AB  - Three anion exchanger expanded bed adsorption (EBA) matrices: Streamline DEAE,
      Streamline Q XL and Q Hyper Z were evaluated with the aid of EFGP from an
      ultrasonic homogenate of Escherichia coli. Two pH of buffer were tested. Capture
      was done in an expanded mode whereas elution was done in a packed mode. The same
      conditions were chosen for evaluation of the three matrices. We observed a loss
      of EGFP (8-15%) in the through flow fraction especially with the Streamline Q XL
      matrix, probably due to an aggregation of beads during sample application. The
      beads of this matrix possess tentacles which probably retain a lot of cellular
      and molecular debris. The two other matrices gave a good purification of the EGFP
      (7-15-fold) but the Q Hyper Z matrix appeared to give the best results. It is
      composed of little size and density beads which lead to a higher exchange surface
      and then a better mass transfer.

PMID- 15236692
TI  - Separation of cobalt binding proteins by immobilized metal affinity
      chromatography.
AB  - Cobalt binding proteins from mouse liver, which were expressed in response to
      CoCl2 poisoning, were separated using gel permeation chromatography and then
      immobilised metal ion affinity chromatography (IMAC) with immobilized cobalt
      ions. Conditions used in IMAC-Co2+ were optimised. The fractions eluted with 60
      mM imidazole were analysed by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE). Differences between the samples were also evaluated
      by a two-dimensional electrophoresis. Samples from the Co2+-treated mice provided
      higher number of electrophoretic spots than those from the untreated mice.
      Relative molecular masses of these proteins are appropriately 37,000; 32,000 and
      26,000 and their isoelectric points (pI) are 6.5-7.5.

PMID- 15236693
TI  - Purification of human galectin-1 produced in high-cell density cultures of
      recombinant Escherichia coli: a comparison with classic shake flask cultivation.
AB  - The aim of the present work was to develop a highly productive and simplified
      process for active human galectin-1 (Gal1) production. Gal1 is a beta-galactoside
      binding lectin that differentially affects biological and cellular functions such
      as immune surveillance and apoptosis. These effects have attracted the attention
      of researchers in cell biology, biochemistry and immunology. However, the
      production of sufficient amounts of recombinant human Gal1 (rhGal1) is needed to
      study of the effects of Gal1 during cell treatments. To this end, an high-yield
      expression of rhGal1 was achieved by high-cell density fed-batch cultivation
      using an exponential glycerol feeding strategy and rhGal1 was purified by a one
      step purification scheme using affinity chromatography.

PMID- 15236694
TI  - Penicillin acylase purification with the aid of hydrophobic charge induction
      chromatography.
AB  - The aim of this work was to test a chromatographic support, 4-mercaptoethyl
      pyridine (4-MEP) Hypercel, for penicillin acylase purification by using pure
      penicillin acylase and crude extract. Two equilibration buffers with various salt
      concentrations and different flow rates were tested. The relationships between
      electrostatic and hydrophobic interactions and proteins are demonstrated.
      (NH4)2SO4 proved preferable because no salting-in occurred, contrary to NaCl. The
      recovery and purification fold were similar to those obtained in pseudo-affinity
      chromatography with a three-fold reduction of the (NH4)2SO4 concentration.

PMID- 15236695
TI  - Analysis of liquid extracts from tree and grass pollens by capillary
      electromigration methods.
AB  - Capillary electromigration methods, zone electrophoresis (CZE), micellar
      electrokinetic chromatography (CMEKC) and isotachophoresis (CITP), have been used
      for analysis of water and water-buffer extracts from tree-common birch (Betula
      verrucosa) and grass-orchardgrass (Dactylis glomerata) pollen samples. Water
      extracts were analyzed by CZE using acetic acid as background electrolyte (BGE),
      by CMEKC in tris-phosphate BGE with anionic detergent sodium dodecyl sulfate
      (SDS) micellar pseudophase (TP-SDS) and by CITP in cationic mode with
      leading/terminating cations K+/BALA+ (beta-alanine (BALA)) and in anionic mode
      with leading/terminating anions Cl-/MES- (2-(N-morpholino)ethanesulphonic acid
      (MES)). Moreover, acetic acid extracts were analyzed by CZE using acetic acid as
      BGE, and alkaline water-SDS-buffer extracts were analyzed by CMEKC using TP-SDS
      as BGE. Extracted amounts of pollen allergens and other UV-absorbing compounds
      and the number of resolved components were evaluated from CZE, CMEKC and CITP
      analyses of the liquid extracts. Larger amounts of UV-absorbing material were
      found in the water-buffer pollen extracts than in the water extracts. More UV
      absorbing material was found in all extracts from D. glomerata pollen than in
      relevant extracts from B. verrucosa pollen. It was found by CITP that the
      extracted amounts of anionic components and their number were much higher than
      those of cationic components. Concentrations of some inorganic ions (e.g. Cl-,
      K+, Na+, Ca2+) in pollen samples were also determined by CITP.

PMID- 15236696
TI  - Disasters happen: would you know what you can do?

PMID- 15236697
TI  - Disaster preparedness: what do we do now?
AB  - Disasters are events that exceed the capacity of the people affected to recover
      from the adverse affects. Understanding types of disasters and components of
      disaster responses provides a basis for developing disaster preparedness plans.
      Disaster preparedness is a process for assessing risks and capacities for
      responding when disasters occur. Planning can mitigate damages and facilitate
      rapid and effective disaster response services. Health care workers, including
      midwives and women's health care providers, can access resources to be prepared
      as competent responders in disaster contexts to meet the needs of women and their
      communities.

PMID- 15236698
TI  - Status of women and infants in complex humanitarian emergencies.
AB  - Women and children bear the greatest burden in the midst of war and long-term
      disasters. Complex humanitarian emergencies are characterized by social
      disruption, armed conflict, population displacement, collapse of public health
      infrastructure, and food shortages. Humanitarian assistance for refugees and
      internally displaced populations requires particular attention to the common
      issues affecting morbidity and mortality in women and infants. Gender-based
      violence and reproductive health concerns are discussed within the context of
      populations affected by conflict and forced migration. Recommendations for
      midwives and women's health care providers engaging in care for women and
      children in complex humanitarian emergencies are discussed.

PMID- 15236699
TI  - Pregnancy and childbirth care following conflict and displacement: care for
      refugee women in low-resource settings.
AB  - Women in developing countries experience the same problems during pregnancy and
      childbirth and die of the same complications, regardless of whether they live in
      stable situations or in situations of conflict and displacement. They need
      services and/or care during pregnancy and childbirth wherever they are and in
      whatever circumstances prevail. This article provides an overview of the Safe
      Motherhood Initiative, including the recent directions taken to prevent maternal
      and neonatal mortality and morbidity. In addition, pregnancy and childbirth care
      in complex humanitarian emergencies is examined, highlighting the experiences in
      refugee settings. In some of these settings, pregnancy outcomes have been better
      than in host or home countries. The challenge remains to ensure that good-quality
      pregnancy and childbirth care, in line with the global standards set for
      achieving safe motherhood, is consistently available and accessible to women
      affected by complex humanitarian emergencies.

PMID- 15236700
TI  - Continuous female companionship during childbirth: a crucial resource in times of
      stress or calm.
AB  - Continuous support by a lay woman during labor and delivery facilitates birth,
      enhances the mother's memory of the experience, strengthens mother-infant
      bonding, increases breastfeeding success, and significantly reduces many forms of
      medical intervention, including cesarean delivery and the use of analgesia,
      anesthesia, vacuum extraction, and forceps. The contribution of doula care has
      become increasingly available in industrial countries and is beginning to be
      adopted in hospitals in underdeveloped countries. Research continues to
      demonstrate the far-reaching value of supportive companionship as a corollary to
      professional health care during birth. Mothers who are at risk because of medical
      or social factors and those delivering in situations of stress, including
      disasters, can benefit greatly from labor support.

PMID- 15236701
TI  - Newborns in adverse conditions: issues, challenges, and interventions.
AB  - Neonatal mortality is intolerably high in developing countries and in situations
      of crisis or disaster as a result of inequity, poverty, and lack of health care
      services. A series of effective, low-cost interventions, based on appropriate
      technologies can be used to address the main causes of neonatal deaths. Among
      these interventions, promotion of exclusive breastfeeding and thermal control of
      the newborn infant are very effective ones. Although the effectiveness of
      interventions such as kangaroo mother care, newborn resuscitation, and infant
      massage is not widely recognized, they may have important complementary roles in
      providing heath care to newborn infants in adverse conditions.

PMID- 15236702
TI  - Providing a nurturing environment for infants in adverse situations: multisensory
      strategies for newborn care.
AB  - Giving birth in dangerous settings, such as natural disasters and war, can have
      long-lasting consequences on infant growth and development. It is during birth
      and the neonatal period that mother and baby are particularly vulnerable to
      environmental stressors. This article explores the neurohormonal aspects of
      stress and social bonding and offers strategies aimed at reducing maternal and
      infant stress and improving the mother-infant relationship. Low-tech
      interventions, such as massage, Kangaroo Mother Care, and multisensory
      intervention (maternal voice, massage, eye-to-eye contact, and rocking) are
      described for their use in adverse environments.

PMID- 15236703
TI  - Resources for providing care for women and infants in disasters and low-resource
      settings.

PMID- 15236704
TI  - Guidelines for parents and caregivers after traumatic events.

PMID- 15236705
TI  - Giving birth "in place": a guide to emergency preparedness for childbirth.

PMID- 15236706
TI  - Publication of science, terror, and the first amendment.

PMID- 15236707
TI  - Prevention and treatment of postpartum hemorrhage: new advances for low-resource
      settings.
AB  - Postpartum hemorrhage due to uterine atony is the primary direct cause of
      maternal mortality globally. Management strategies in developed countries involve
      crystalloid fluid replacement, blood transfusions, and surgery. These definitive
      therapies are often not accessible in developing countries. Long transports from
      home or primary health care facilities, a dearth of skilled providers, and lack
      of intravenous fluids and/or a safe blood supply often create long delays in
      instituting appropriate treatment. We review the evidence for active management
      of third-stage labor and for the use of specific uterotonics. New strategies to
      prevent and manage postpartum hemorrhage in developing countries, such as
      community-based use of misoprostol, oxytocin in the Uniject delivery system, the
      non-inflatable antishock garment to stabilize and resuscitate hypovolemic shock,
      and the balloon condom catheter to treat intractable uterine bleeding are
      reviewed. New directions for clinical and operations research are suggested.

PMID- 15236708
TI  - Perceptions matter: barriers to treatment of postpartum hemorrhage.
AB  - Postpartum hemorrhage is the leading cause of maternal deaths in developing
      countries. This report highlights the social and cultural factors that influence
      the decision to seek care in cases of postpartum bleeding. Survey data on
      awareness of danger signs in the postpartum period and findings from the
      anthropologic literature describing beliefs about bleeding in childbirth and the
      postpartum period are presented. Findings point to a mismatch between actual and
      perceived risks of danger in the postpartum period. This may reflect a viewpoint
      that there are few risks remaining after the baby is born. This may, in turn,
      shape the perception that the postpartum period is one in which less vigilance is
      required compared with labor and birth. Such beliefs are important to consider,
      as they may influence timely seeking of emergency obstetric care. Efforts to
      reduce the incidence of postpartum hemorrhage as a major cause of maternal death
      must progress on two fronts: on the supply side to ensure the provision of
      skilled care and on the demand side to ensure that women and their families
      accept the view that bleeding after birth is dangerous and that skilled care is
      preferable to traditional care.

PMID- 15236709
TI  - Does traditional birth attendant training increase use of antenatal care? A
      review of the evidence.
AB  - A combined narrative review and metanalytic review was conducted to summarize
      published and unpublished studies completed between 1970 and 2002 on the
      relationship between traditional birth attendant (TBA) training and increased use
      of professional antenatal care (ANC). Fifteen studies (n = 15) from 8 countries
      and 2 world regions were analyzed. There are, to varying degrees, positive
      associations between TBA training and TBA knowledge of the value and timing of
      ANC services, TBA behavior in offering advice or assistance to obtain ANC, and
      compliance and use of ANC services by women cared for by TBAs or living in areas
      served by TBAs. There is a serious lack of information about TBA training program
      characteristics. Although the findings cannot be causally attributed to TBA
      training, the results suggest that training may increase ANC attendance rates by
      about 38%. This magnitude of improvement could contribute to a reduction in
      maternal and perinatal mortality in areas where women have access to quality
      antenatal and emergency obstetric care. There is an urgent need to improve
      capacity for evaluation and research of the effect of TBA training programs and
      other factors that influence women's use of ANC services.

PMID- 15236710
TI  - Effect of shifting policies on traditional birth attendant training.
AB  - Traditional birth attendant (TBA) training commenced in many places in the non
      Western world in the 1970s, supported by the World Health Organization and other
      funding bodies. By 1997, senior policy makers decided to refocus priorities on
      the provision of "skilled attendants" to assist birthing women. The definition of
      skilled attendants excluded TBAs and resulted in the subsequent withdrawal of
      funding for TBA training globally. A review of the health and sociological
      literature and international policy documents that address TBA training revealed
      how international policy and professional orientation are reflected in education
      programs designed for the TBA. Policy makers risk ignoring the important cultural
      and social roles TBAs fulfill in their local communities and fail to recognize
      the barriers to the provision of skilled care. The provision of skilled
      attendants for all birthing women cannot occur in isolation from TBAs who in
      themselves are also highly skilled. This article argues a legitimacy of
      alternative worldviews and acknowledges the contribution TBAs make to
      childbearing women across the world.

PMID- 15236711
TI  - Pathways of decision making among Yucatan Mayan traditional birth attendants.
AB  - In rural, developing world communities, women are often isolated from biomedical
      services. Frequently, traditional birth attendants (TBAs) are the only caregivers
      during childbirth, both normal and complicated. Women trust their TBAs to manage
      their births. Globally, government and non-governmental organizations (NGOs) have
      sought to upgrade TBAs' skills and to encourage them to refer complications.
      However, most training programs have failed to change TBAs' practice
      substantially. Logistical barriers in reaching biomedical services in a timely
      manner are a key issue. Another is the difference between biomedical and
      traditional practitioners in the cognitive frameworks that shape decision making
      and management behaviors. The purpose of this study, conducted in Quintana Roo
      State, Mexico, was to listen to the voices of practicing Yucatec Maya TBAs
      (parteras) as they described decision making and management of complicated
      births. In-depth interviews with six practicing parteras in rural, isolated
      communities revealed that the parteras used traditional Maya ethnomedicine while
      valuing biomedical approaches. We isolated themes in decision making and mapped
      management of birth complications. Integrating TBAs' traditional knowledge into
      biomedical training programs is one way to honor their knowledge and make
      training relevant.

PMID- 15236712
TI  - The American College of Nurse-Midwives' home-based lifesaving skills program: a
      review of the Ethiopia field test.
AB  - The Home-Based Lifesaving Skills program (HBLSS) is a family- and community
      focused, competency-based program that aims to reduce maternal and newborn
      mortality by increasing access to basic lifesaving measures within the home and
      community and by decreasing delays in reaching referral facilities where
      obstetric complications, such as postpartum hemorrhage and newborn asphyxia, can
      be managed. HBLSS was field tested in rural southern Ethiopia where over 90% of
      births take place at home with unskilled attendants. The program review assessed
      1) the performance of HBLSS-trained guides; 2) management of postpartum
      hemorrhage and newborn infection by women, family, and birth attendants; 3)
      exposure of women and families to HBLSS training; and 4) community support. There
      was improved performance in management of postpartum hemorrhage, a leading cause
      of maternal death. Findings for management of newborn infection were less
      compelling. None of the communities had established reliable emergency
      transportation. Exposure to HBLSS training in the community was estimated at 38%,
      and there was strong community support. Organizations incorporating HBLSS into
      proposals focusing on maternal and newborn health during birth and the immediate
      postpartum period are encouraged to conduct research necessary to establish the
      evidence base for this promising new approach.

PMID- 15236713
TI  - Cervical cancer screening in low resource settings using visual inspection with
      acetic acid.
AB  - Cervical cancer is one of the leading causes of death for middle-aged women in
      the developing world, yet it is almost completely preventable, if precancerous
      lesions are identified and treated in a timely manner. Cervical cancer screening
      based on cytologic examination is largely unavailable in developing countries or
      made available to a small, select group of women in private facilities, maternal
      child health sites, or family-planning clinics, missing the age groups at highest
      risk for precancerous lesions. Visual inspection with acetic acid (VIA) can be
      used to screen women. It can be done by nurses or midwives with appropriate
      training. Although still under investigation, research results show that VIA is
      simple, accurate, cost-effective, and acceptable to most women. This article
      reviews the natural history of cervical cancer and important aspects to consider
      related to cervical cancer screening in low resource settings. The VIA technique
      is described in detail.

PMID- 15236714
TI  - Safe motherhood program evaluation: theory and practice.
AB  - Debate on the evaluation of safe motherhood programs has mainly focused on the
      outcome or process measure to be used. Less attention is paid to the application
      of different approaches to evaluation. This article reviews current theories of
      evaluation and provides examples of the extent to which these theories have been
      applied in the actual practice of evaluation. Most evaluations use multiple
      methods and approaches, but the rationale and intention behind these choices are
      often not made explicit. Factors are identified that need to be taken into
      consideration when planning and conducting safe motherhood program evaluations.
      Safe motherhood programs are complex interventions, requiring evaluation by
      different theoretical approaches and multiple methods. Awareness of these
      approaches will allow health professionals to plan for evaluation and to use
      evaluation findings more effectively. If cognizant of the different approaches to
      evaluation, evaluation frameworks can be developed to improve assessment of the
      effectiveness of these programs.

PMID- 15236715
TI  - Somali refugee women speak out about their needs for care during pregnancy and
      delivery.
AB  - More than half of all Somali refugees in the United States live in Minnesota. To
      obtain information to develop culturally sensitive health education materials, we
      conducted two focus groups with 14 Somali women who had each given birth to one
      child in Minnesota. Overall, women thought that their childbirth experience was
      positive. They also reported racial stereotyping, apprehension of cesarean
      births, and concern about the competence of medical interpreters. Women wanted
      more information about events in the delivery room, pain medications, prenatal
      visits, interpreters, and roles of hospital staff. The most desirable educational
      formats were a videotape, audiotapes, printed materials, and birth center tours.
      To increase their attendance at prenatal appointments, participants said they
      needed reminder telephone calls, transportation, and childcare.

PMID- 15236716
TI  - Determinants of women's decision making on whether to treat nausea and vomiting
      of pregnancy pharmacologically.
AB  - Nausea and vomiting of pregnancy (NVP) affects up to 80% of all women to some
      degree during their pregnancies. Diclectin (doxylamine and pyridoxine [vitamin
      B6]) has been on the Canadian market for many years and is indicated as the drug
      of choice for the treatment of NVP. However, some women choose not to treat NVP
      with pharmacologic measures, perhaps due to a persistent fear of teratogenic
      risk. The objective of this study was to determine the factors that influence a
      woman's decision not to treat NVP with pharmacologic measures. Fifty-nine women
      recruited from the Motherisk Nausea and Vomiting Helpline completed a
      questionnaire. All were informed that Diclectin was considered safe for use
      during pregnancy. At a follow-up telephone call, 34% were not using any
      pharmacologic treatment, and of those who were taking the drug, 26% were using
      less than the recommended dose. Reasons cited for not using the medication were
      insufficient safety data, preference for non-pharmacologic methods, and being
      made to feel uncomfortable by the physician. Of the women who did use Diclectin,
      the most convincing reassuring information that it was safe to use came from
      friends and family. Many other factors play a large role in a women's decision
      making.

PMID- 15236718
TI  - Mucolipidosis type IV a rare genetic disorder: new addition to the Ashkenazi
      Jewish panel.
AB  - Mucolipidosis type IV (MLIV) is a rare genetic disorder that primarily affects
      persons of Ashkenazi Jewish descent. Current information available about testing
      options and the Ashkenazi Jewish Screening panel, including the addition of
      screening for MLIV, is presented. The importance of genetic screening and
      counseling is emphasized.

PMID- 15236717
TI  - Polyethylene glycol electrolyte solution (Isocolan) for constipation during
      pregnancy: an observational open-label study.
AB  - To evaluate the efficacy of a polyethylene glycol electrolyte solution (PEG-4000)
      in pregnant women affected by constipation, 40 consecutive pregnant women from 6
      to 38 weeks' gestation were enrolled in this preliminary study. Constipation was
      defined as spontaneous evacuation less than four times a week or the presence of
      symptoms such as defecation pain, rectal urgency, tenesmus, anal injury, or
      abdominal pain. A PEG-4000 solution (Isocolan, also marketed in the United States
      as Golitely/Nulitely) was administered for 15 days at a dose of 250 mL by mouth
      once or twice a day. The number of bowel movements per week, the presence or
      absence of liquid stools, tenesmus, urgency, defecation pain, anal lesions, and
      abdominal pain were evaluated before and after 15 days of treatment. Treatment
      with PEG-4000 significantly increased the evacuation episodes per week (from 1.66
      +/- 0.48 to 3.16 +/- 1.05; P <.01), and constipation was resolved in 27 of 37
      women (73%). Defecation pain, anal injury, and abdominal pain significantly
      improved after PEG-4000 administration. Improvement occurred in both patients
      with new-onset constipation during pregnancy as well as patients with a history
      of constipation before pregnancy. These preliminary findings indicate that PEG
      4000 may be an effective choice for the treatment of constipation during
      pregnancy.

PMID- 15236719
TI  - Care of women with female circumcision.

PMID- 15236725
TI  - Palliative care: an essential aspect of quality cancer care.
AB  - The past 2 decades in the United States have witnessed major developments in
      palliative care. Despite major advances in the early detection and treatment of
      cancer, more than 550,000 people in the United States die each year from cancer.
      For most of these patients,treatment in the last months of life is focused on
      attempts to achieve comfort rather than on treatment aimed at cure of disease.
      This article discusses the goals of palliative care, the progress that has been
      made in meeting these goals, and the progress that still needs to be made.

PMID- 15236726
TI  - Methodology for scientific evaluation of palliative surgery.
AB  - Measuring the success of surgical palliation is not straightforward.To measure
      the benefits as well as limitations of surgical palliation,surgeons need outcome
      assessments other than the existing traditional measures of 30-day surgical
      morbidity and mortality and 5-year survival. This article delineates a scientific
      method of evaluating and measuring surgical palliation and shares techniques and
      pitfalls of assessment gained from prior experience.

PMID- 15236727
TI  - Surgical palliation of thoracic malignancies.
AB  - Primary and metastatic thoracic malignancies are often incurable. Surgeons caring
      for these patients must be familiar with the options,indications, techniques, and
      limitations of interventions for palliative treatments in these patients. This
      article is an overview of the current practices for palliation of a broad
      spectrum of complaints relating to patients with carcinomas of the lung,
      esophagus,and mesothelium. The information can be used for treatment of patients
      with complaints secondary to less common malignancies and metastatic disease of
      the thorax.

PMID- 15236728
TI  - Gastrectomy for gastric cancer: defining critical elements of patient selection
      and outcome assessment.
AB  - In advanced gastric cancer, palliation of symptoms, rather than cure, is often
      the most appropriate goal of patient management. There are important differences
      among patients undergoing non-curative operations for gastric cancer. The
      literature to date is limited, in part, by imprecise use of the term palliative.
      In clinical decision-making, the potential benefits of proposed procedure must be
      balanced against the duration of hospitalization, treatment of complications, and
      requirements for additional palliation. Studies designed to measure palliative
      interventions would benefit from precise designations of palliative intent
      inpatients receiving non-curative operations.

PMID- 15236729
TI  - Palliative care for colorectal cancer.
AB  - Most patients with stage IV colorectal cancer have a poor prognosis,but numerous
      palliative modalities are available today. When a cure is no longer possible,
      treatment is directed toward providing symptomatic relief. The data leave little
      doubt that surgical resection may provide good palliation. Although resection has
      been the mainstay of palliative care, an individualized multidisciplinary
      approach, which may involve both surgical and nonsurgical modalities, is probably
      the best current option.

PMID- 15236730
TI  - Surgical management of malignant bowel obstruction.
AB  - MBO is a common but difficult problem for surgeons caring for cancer patients.
      Nonsurgical interventions should be considered in all patients with MBO,
      especially inpatients with limited survival or for whom surgery will have little
      effect on disease control. Although there is no algorithm for all patients with
      MBO, decision-making is based on reasonable expectations of survival and
      treatment-related success. Surgical options can be helpful in the setting of MBO
      as long as reasonable goals and realistic outcomes are clear.

PMID- 15236731
TI  - Palliative therapy for pancreatic/biliary cancer.
AB  - Palliative treatment for unresectable pancreatic and biliary cancer is most
      typically directed at symptoms of local invasion, including obstructive jaundice,
      duodenal obstruction, and cancer-related pain. Surgical and nonsurgical
      therapeutic options should be considered depending on the individual situation.
      As with all treatment planning, palliative therapy should be planned using a
      multidisciplinary approach, including input from the surgeon,
      gastroenterologist,radiologist, and medical and radiation oncologist.

PMID- 15236732
TI  - Palliative techniques for hepatic cancer.
AB  - Primary and secondary hepatic malignancies are a leading cause of death. Only a
      minority of patients with liver cancer are candidates for curative surgical
      resection. Palliative treatments for unresectable hepatic malignancies should
      minimize tumor-related symptoms and extend overall survival. Systemic
      chemotherapy is only modestly effective at both ameliorating symptoms and
      improving survival. This review focuses on the liver-directed therapy options for
      patients with advanced unresectable liver malignancies.

PMID- 15236733
TI  - Palliative approaches to the patient with breast cancer.
AB  - Despite an increasing trend towards early diagnosis of breast cancer,patients
      still present with locally advanced disease. Also, in some patients chemotherapy
      will fail, and local and regional recurrence will occur. This article outlines
      options for palliative care for such patients.

PMID- 15236734
TI  - Palliative surgery of soft tissue sarcoma.
AB  - Despite an increasing trend towards early diagnosis of breast cancer,patients
      still present with locally advanced disease. Also, in some patients chemotherapy
      will fail, and local and regional recurrence will occur. This article outlines
      options for palliative care for such patients.

PMID- 15236735
TI  - Major palliative amputations.
AB  - The role of major amputations in the palliative care of cancer patients remains
      controversial. Major amputations result in loss of function, frequently require
      prolonged recovery, and are associated with major morbidity or mortality.
      Therefore, it may seem that major amputations should be rarely recommended for
      the palliation of cancer patients. Hence, we attempt to establish the
      indications,management, and outcomes of major amputations in the palliative
      management of cancer patients.

PMID- 15236738
TI  - Strong links are important, but weak links stabilize them.

PMID- 15236739
TI  - The PA14 domain, a conserved all-beta domain in bacterial toxins, enzymes,
      adhesins and signaling molecules.

PMID- 15236740
TI  - DCC proteins: a novel family of thiol-disulfide oxidoreductases.

PMID- 15236741
TI  - Evolutionary origins of the RNA-guided nucleotide-modification complexes: from
      the primitive translation apparatus?

PMID- 15236742
TI  - Microbial H2O2 sensors as archetypical redox signaling modules.

PMID- 15236743
TI  - The rocky roots of the acetyl-CoA pathway.

PMID- 15236744
TI  - Dealing with mechanics: mechanisms of force transduction in cells.

PMID- 15236745
TI  - Calcium-mediated cellular signals: a story of failures.

PMID- 15236746
TI  - Redox-driven membrane-bound proton pumps.

PMID- 15236747
TI  - Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T
      cells: analysis using depleting antibodies.
AB  - Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the
      C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte
      glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of
      one week and supplemented with Bordetella pertussis toxin given IV. Here, we
      studied the effect on the induction of EAE of depleting antibodies to CD4, CD8,
      or CD25 administered before either the first or the second dose of MOG p35-55. We
      found that anti-CD4 abolished EAE when given before the first immunization; anti
      CD4 did not affect the disease when it was given before the second immunization.
      Anti-CD8 enhanced EAE induction when given before either of the two
      immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given
      before the first immunization, but anti-CD25 was even more effective in enhancing
      EAE when given before the second immunization. The anti-CD25 treatment led to
      significantly enhanced IFNgamma production by T cells responding to MOG p35-55
      and persisting anti-MOG antibodies detectable 56 days after the first
      immunization. Administration of anti-CD8 or anti-CD25 abolished the need for
      pertussis toxin to induce EAE. These findings are compatible with the idea that
      CD4 T cells are required for the initial induction of EAE and that the disease is
      down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist
      prior to MOG immunization, but the CD25+ regulators appear to be further
      amplified by immunization.

PMID- 15236748
TI  - NOD macrophages produce high levels of inflammatory cytokines upon encounter of
      apoptotic or necrotic cells.
AB  - During the development of type 1 diabetes, pancreatic beta-cells are subject to
      an immune attack, leading to their apoptotic or necrotic cell death. Apoptotic
      beta-cells are also present during periods of tissue remodeling, such as in early
      life. Macrophages should clear apoptotic cells silently without production of pro
      inflammatory cytokines. The aim of the present study was to investigate the
      cytokine pattern of NOD macrophages exposed to apoptotic or necrotic cells in
      vitro. In contrast to the limited response of macrophages from C57BL/6 or NOR
      mice, NOD macrophages reacted aberrantly to both necrotic and apoptotic cells,
      with secretion of inappropriately high amounts of IL1beta and TNFalpha. Further
      exploration of the macrophage behavior showed an excessive response of NOD
      macrophages when exposed to LPS (high iNOS and IL12p40 levels), accompanied by
      hyper-activation of NF-kappaB(p65). In contrast, NOD macrophages failed to up
      regulate IL1beta and IL12p40 in response to IFNgamma. This failure correlated
      with low protein levels and a low phosphorylation state of STAT1alpha. We
      conclude that NOD macrophages have severely aberrant cytokine expression patterns
      that could contribute to the initiation or continuation of an immune attack
      towards the pancreatic beta-cells and thus onset and progression of type 1
      diabetes.

PMID- 15236749
TI  - Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal
      models of type 1 diabetes.
AB  - Mice have two insulin genes that differ in the insulin sequence by two amino
      acids, including the B9 position. Given prior studies of the B:9-23 insulin
      peptide in NOD mice, a fundamental question is whether the immune response to the
      B:9-23 peptide of the two insulins is identical. We investigate responses to the
      immunization with B:9-23 insulin 1 and 2 peptides in NOD and RIP-B7.1 Balb/c
      mice. NOD and F1 (Balb/c x C57/Bl6) B7.1 transgenic mice were given either B:9-23
      insulin 1, B:9-23 insulin 2 or tetanus toxoid (TT) control peptide. Insulin
      autoantibodies (IAA), and anti-B:9-23 antibodies (IgG1 and IgG2c) were measured.
      Subcutaneous injection of the insulin 2 but not the insulin 1 peptide
      significantly protected NOD mice from diabetes. Conceptually similar, insulin 1
      peptide immunization accelerated diabetes in the B7.1 mice compared with insulin
      2 peptide. Insulin 1 and 2 peptides induced similar levels of IAA in the NOD mice
      except at week 26, where insulin 2 induced higher levels of IAA. Anti-IgG1 B:9-23
      peptide antibodies were higher in the insulin 2 immunized group of NOD mice,
      while IgG2c anti-B:9-23 peptide antibodies were higher in the insulin 1 group.
      Adoptive transfer of splenocytes from insulin 1 immunized mice to NOD.scid mice
      demonstrated accelerated diabetogenicity. The protection afforded by insulin 2
      peptide but not insulin 1 peptide in the NOD mouse is reflected by its
      predominant Th2 humoral response. This may relate to the protection conferred by
      the insulin 1 knockout when bred onto NOD mice in contrast to acceleration of
      disease with an insulin 2 knockout.

PMID- 15236750
TI  - Early events in islets and pancreatic lymph nodes in autoimmune diabetes.
AB  - The specific contributions of islet cell microenvironment during the development
      of autoimmune type 1 diabetes remain unclear. The aims of this study were to
      identify early immune-driven abnormalities in islets and pancreatic lymph nodes
      of NOD mice by cDNA arrays. We compared gene expression profiles of purified
      islets and pancreatic lymph nodes of 4-week-old NOD mice to NOD-SCID and BALB/c
      mice. To further characterize the networks implicated in beta-cell destruction,
      we also performed a time-course analysis using islets and pancreatic lymph nodes
      of NOD mice from 2 to 25 weeks of age. We found consistent changes by cDNA arrays
      and RT-PCR analyses among islet genes before the detection of CD3+ T cells in the
      islet periphery associated with dendritic cell attraction, lymphocyte homing, and
      apoptosis. In contrast to IL-1, TYNFSF13B and osteopontin genes which were
      specifically activated, the immunoregulatory cytokine IL-11 was poorly detected
      in NOD islets and pancreatic lymph nodes. Genes involved in angiogenesis were
      also specifically activated in NOD islets of 2 and 4 weeks of age. The present
      time-course macroarray and RT-PCR analyses provides a detailed picture of the
      different genes involved in autoimmune diabetes and illustrates the importance of
      islet cell microenvironment that prepares the late beta-cell destruction.

PMID- 15236751
TI  - Efficacy of peripheral tolerance induced by dendritic cells is dependent on route
      of delivery.
AB  - Previous studies have demonstrated that the route of delivery of dendritic cells
      (DC) is an important variable in eliciting anti-tumor immunity. In contrast,
      little is known about different routes of DC administration to influence
      peripheral tolerance in autoimmune diseases. Here we compared therapeutic effect
      of splenic IFN-gamma-modified-DC (IFN-gamma-DC) in actively induced experimental
      allergic encephalomyelitis (EAE) by different routes of DC delivery. Following
      subcutaneous (s.c.) injection, IFN-gamma-DC effectively suppressed clinical signs
      of EAE, whereas intravenous (i.v.) injection did not inhibit clinical signs of
      EAE. Compared to s.c. injection, i.v. injection of IFN-gamma-DC failed to mediate
      T cell responses, but stimulated anti-MBP antibody production and upregulated pro
      inflammatory IL-1beta, IFN-gamma and TNF-alpha as well as RANTES expression which
      may contribute to the accumulation of inflammatory cells within the central
      nervous system. These results suggest that the administration route of DC should
      be considered as an important factor for DC-based immunotherapy in autoimmune
      diseases.

PMID- 15236753
TI  - Precursor frequencies of T-cells reactive to insulin in recent onset type 1
      diabetes mellitus.
AB  - T-cell mediated autoimmune beta-cell destruction is an important component of
      type 1 diabetes (T1D) and insulin is a critical antigen recognized by
      autoreactive T-cells. The aim of this study was to investigate the precursor
      frequency of insulin reactive T-cells in type 1 diabetes. We studied 19 T1D
      patients, 12 age-matching non-diabetic healthy siblings and 12 non-diabetic
      healthy parents. Limiting dilution analysis (LDA) was performed to insulin and
      tetanus toxoid (TT). A progressive decrease in the number of negative cultures at
      increasing cell concentrations that is represented by a low goodness-of-fit (GoF,
      low Chi-square), was seen with the TT response in all three groups; precursor
      frequencies and GoF were similar in patients, siblings, and parents. Reactivity
      to insulin, however, showed low precursor frequencies in patients and siblings
      and the LDA to insulin demonstrated dramatic decreases in the number of positive
      cultures at higher cell concentrations leading to a high GoF in patients and
      siblings compared to parents. This saw-toothed pattern of reactivity to insulin
      is indicative of multiple hit kinetics and implies that the response is
      regulated. Consequently the precursor frequency of insulin autoreactive cells in
      patients and their siblings is probably much higher than calculated.

PMID- 15236752
TI  - Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in
      type 1 diabetic subjects.
AB  - Active T cell recognition of islet antigens has been postulated as the pathogenic
      mechanism in human type 1 diabetes, but evidence is scarce. If T cells are
      engaged, they are expected to display increased clonal size and exhibit a T
      helper (Th)1/Th2 differentiation state. We used a peptide library that covers
      tyrosine phosphatase IA-2, a target antigen expressed in pancreatic beta cells,
      to probe 8 diabetic patients and 5 HLA-matched controls. When tested in a high
      resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number
      of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in
      controls and IL-4 producing cells were not present. An average of 9 peptides was
      recognized in the patients vs. one in the controls. Determinant recognition
      primarily involved CD4+ cells and showed high variability among the patients.
      Furthermore, anti-CD28 antibody signal enhances quantitative assessment of
      effector T cells in T1D patients. In vitro expansion with peptides and IL-2
      results in detection of responding cells in the controls and loss of disease
      specificity of the T cell response. Together these data provide strong evidence
      for the active targeting of IA-2 by Th1 memory effector cells in human type 1
      diabetes.

PMID- 15236754
TI  - Characterization of the immunoreactivity of anti-interferon alpha antibodies in
      myasthenia gravis patients. Epitope mapping.
AB  - Cytokines, such as interferons (IFN), underlie many immunological functions and
      are increasingly implicated in disease-related symptoms and pathology. In order
      to study the potential roles of IFN alpha and its antagonists in autoimmune
      phenomena, the sera from 89 patients (aged 15-95 years, 65 females) diagnosed as
      having myasthenia gravis (MG) (2 months to 34 years duration) were tested for the
      presence of natural anti-IFN alpha-2b auto-antibodies. Sera were screened for
      anti-IFN alpha-2b by a sandwich-type enzyme immunoassay system. Ten (11.2%) and 6
      (6.7%) sera were identified that contained positive-competing and non-competing
      anti-IFN alpha-2b auto-antibodies, respectively. The MG sera were further
      analyzed by immunobloting against reduced IFN alpha-2b and for neutralizing anti
      IFN alpha activity in an antiviral assay cells system. From tested EIA positive
      competing sera, 5 were shown to be positive by immunoblot and 6 sera were found
      to contain neutralizing anti-IFN alpha-2b. Four of the 6 neutralizing anti-IFN
      alpha-2b sera came from patients with thymoma-associated MG. The sera were
      studied for linear epitope recognition on the IFN alpha-2b molecule by a solid
      phase binding assay, in which overlapping peptides homologous with the entire IFN
      alpha-2b sequence were separately synthesized on a nitrocellulose sheet. Peptides
      number 2 (residues 8-21), 3 (15-28), 6 (33-46), 10 (63-76), 15 (98-112), and 21
      (141-154) were immunoreactive. Peptide 21 was apparently associated with
      antiviral activity, although peptide 21 has not been previously described as an
      immunogenic determinant on the IFN alpha-2b molecule. These results indicate that
      neutralizing anti-IFN alpha-2b is often present in MG, particularly in cases of
      thymoma-associated MG, and recognize a variety of epitopes on the IFN alpha-2b
      molecule, including those involved in its biological activity. Two groups of IFN
      epitopes were described associated with patient's age but not with diseases
      evolution.

PMID- 15236755
TI  - Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases:
      implication of TNF -308 gene polymorphism.
AB  - Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT),
      Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as
      multifactorial diseases. In this study, we have examined single and haplotypic
      genetic variation across the major histocompatibility complex (MHC) in a Tunisian
      isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and
      21 with PIM). Genotyping was performed for HLA class I and II alleles as well as
      polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and
      heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association
      of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using
      Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p
      = 0.03). The FBAT has given evidence for genetic association with TNF -308 and
      HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011),
      whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056,
      respectively) were rather implicated in HT pathogenesis. Results found by TDT
      STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD
      pathogenesis (p < 10(-9)).

PMID- 15236756
TI  - Cellular and molecular composition of fibrous capsules formed around silicone
      breast implants with special focus on local immune reactions.
AB  - During the past 30 years, much debate has centered around side effects of
      silicone breast implants. Meta-analyses rejected the presumed relationship
      between silicone breast implants and connective tissues diseases but, in seeming
      contradiction, case reports about connective tissue diseases and rheumatoid
      symptoms continue to be published. We analyzed the cellular and molecular
      composition of fibrous capsules removed from patients at various times after
      surgery for diagnostic purposes (breast cancer relapse) or to relieve painful
      constrictive fibrosis. Frozen sections of capsule tissue were
      immunohistochemically stained for subsets of lymphocytes, macrophages, dendritic
      cells, fibroblasts, smooth muscle cells, for collagenous and non-collagenous
      extracellular matrix proteins, for heat shock protein 60 (HSP60) and for adhesion
      molecules. Massive deposition of fibronectin and tenascin was observed adjacent
      to the implant surface. The capsule/silicone implant contact zone was
      consistently characterized by a palisade-like single or multilayered cell
      accumulation consisting of HSP60+ macrophages and HSP60+ fibroblasts. Mononuclear
      cell infiltrates consisting of activated CD4+ T-cells, expressing CD25 and
      CD45RO, as well as macrophages were detected beneath the contact zone as well as
      perivascularly. Importantly, many Langerhans-cell like dendritic cells (DCs) were
      found with a predilection at the frontier layer zone abutting the silicone
      implant. Also, at this site, massive expression of ICAM-1, but not VCAM-1 or ELAM
      1 emerged. Endothelial cells of the intracapsular neovasculature were P
      Selectin+. Our results show that silicone induces a strong local T-cell immune
      response and future studies will determine the specificity and function of these
      T-lymphocytes.

PMID- 15236757
TI  - The health of normally aging men: The Massachusetts Male Aging Study (1987-2004).

PMID- 15236758
TI  - RNAi: ancient mechanism with a promising future.
AB  - RNA interference (RNAi) is a gene silencing mechanism that has been conserved in
      evolution from yeast to man. Double stranded RNA, which is either expressed by
      cellular genes for small non-coding RNAs, by parasitic nucleic acids, such as
      viruses or transposons, or is expressed as an experimental tool, becomes
      processed into small RNAs, which induce gene silencing by a variety of different
      means. RNAi-induced gene silencing controls gene expression at all levels,
      including transcription, mRNA stability and translation. We are only beginning to
      understand the physiological roles of the RNAi pathway and the function of the
      many small non-coding RNA species, which are found in eukaryotic genomes. Here we
      review the known functions of genes in RNAi in various species, the experimental
      use and design of small RNAs as a genetic tool to dissect the function of
      mammalian genes and their potential as therapeutic agents to modulate gene
      expression in patients.

PMID- 15236759
TI  - Suppressor analysis points to the subtle role of the LAG1 ceramide synthase gene
      in determining yeast longevity.
AB  - Individual yeast cells display a finite replicative capacity. LAG1 was identified
      as a gene that is differentially expressed during the yeast replicative life span
      and was shown to play a role in determining yeast longevity. This gene is not
      essential, but simultaneous deletion of LAG1 and its close homologue LAC1 is
      lethal. Lag1p and Lac1p have been found to be an essential component of ceramide
      synthase. In this study, multicopy suppressors of the lethality of a lag1delta
      lac1delta double mutant were isolated to help clarify the role of LAG1 in yeast
      longevity. The two multicopy suppressors YBR183w (YPC1) and YPL087w (YDC1) encode
      ceramidases unrelated to Lag1p and Lac1p, which were previously found to support
      the reverse reaction of ceramide synthesis. Multiple copies of YPC1 were much
      more efficient than YDC1 in rescuing cell growth. They were also much more
      effective in rescuing the life span of a lag1delta lac1delta double mutant,
      sustaining a life span approaching that obtained by the restoration of LAG1
      expression. Neither deletion of LAC1 nor overexpression of YPC1 had a detectable
      effect on wild-type life span. However, the overexpression of LAG1 had a bimodal
      effect on longevity, with moderate expression resulting in increased longevity
      and with higher expression curtailing life span. These results suggest that
      subtle changes in ceramide/sphingolipid metabolism are important in determining
      yeast longevity. They also indicate that Lag1p plays a special role in this
      relationship. Homologues of Lag1p have been identified in higher eukaryotes,
      including human, raising the possibility that ceramide and other sphingolipid
      metabolites play a wider role in biological aging.

PMID- 15236760
TI  - Lifespan extension by dietary restriction in female Drosophila melanogaster is
      not caused by a reduction in vitellogenesis or ovarian activity.
AB  - Dietary restriction (DR) extends lifespan in a wide range of organisms. DR also
      reduces daily and lifetime fecundity. The latter may be an evolutionary
      adaptation to survive periods of food shortage. Reproductive rate is often
      negatively correlated with lifespan, and a reduced cost of reproduction could be
      the mechanism by which DR extends lifespan. We tested this hypothesis in
      Drosophila melanogaster females, by directly suppressing different aspects of
      reproduction and measuring the effect on the response of lifespan and age
      specific mortality to DR. DR resulted in lifespan extension in females kept with
      males, in females kept without males, in females with vitellogenesis blocked by
      the mutant ovoD1 and in females with no germline as a result of X-irradiation.
      Moreover, rapid (48 h) changes in age-specific mortality, previously seen in
      fertile females switched between full feeding and DR, were also seen in ovoD1
      females. Furthermore, these rapid changes in age-specific mortality in cohorts of
      fertile wild type females were not accompanied by concurrent changes in egg
      production. These results indicate either that reduced reproduction is not
      necessary for lifespan extension by DR in Drosophila females, or that the
      relevant aspects of reproduction act upstream of our interventions and were
      therefore not blocked in our experiments.

PMID- 15236761
TI  - Chronic exposure to morphine produces a marked cardioprotective phenotype in aged
      mouse hearts.
AB  - Aging is often associated with decreased myocardial ischemic tolerance. We
      recently reported that chronic preconditioning produced by continuous exposure to
      morphine affords a profound cardioprotective phenotype in young mice. In this
      study, we determined if chronic exposure to morphine retained its ability to
      precondition the myocardium in the young or aged heart. Young (10-14 weeks) or
      aged (24-26 months) C57/BL6 mice were untreated, administered morphine acutely
      (30 microM), or implanted with a morphine pellet (75 mg) for 5 days prior to
      heart isolation and perfusion. Following equilibration, perfused hearts were
      subjected to 25 min ischemia and 45 min reperfusion. Untreated hearts from both
      young and aged mice displayed marked contractile dysfunction and LDH release
      following reperfusion. Acute infusion of morphine improved recovery of end
      diastolic pressure and developed pressure in young (P < 0.05 vs. untreated) but
      not senescent hearts. Hearts from mice exposed to morphine for 5 days displayed a
      further improvement in post-ischemic contractile function (P < 0.05 vs. acute
      treatment), and a marked reduction in post-ischemic LDH efflux (P < 0.05 vs.
      untreated) in both young and senescent hearts. These data demonstrate that aged
      hearts maintain the ability to be preconditioned by chronic exposure to morphine
      in the absence of acute protection.

PMID- 15236762
TI  - Suppressive effect of green tea catechins on morphologic and functional
      regression of the brain in aged mice with accelerated senescence (SAMP10).
AB  - Green tea catechins (GT-catechins) have been reported to have an antioxidative
      effect. We investigated the effect of long-term GT-catechin intake on aging and
      oxidative damage using aged mice with accelerated senescence (SAMP10), a model of
      brain senescence with cerebral atrophy and cognitive dysfunction. Major atrophy
      was observed in the rhinencephalon, hippocampus and striatum of 12-month-old
      untreated SAMP10 mice. Similarly, levels of 8-oxodeoxyguanosine (8-oxodG), a
      marker of oxidative DNA damage, were higher in these parts of the cerebrum than
      in the cerebral cortex and liver. GT-catechin intake effectively suppressed such
      atrophy in 12-month-old SAMP10 mice. A preventive effect of GT-catechin intake on
      oxidative DNA damage was also observed in the rhinencephalon (an area
      particularly susceptible to atrophy) at 6 months of age, i.e. during the early
      stages of atrophy. A suppressive effect of GT-catechin intake on cognitive
      dysfunction, as determined by the learning time needed to acquire an avoidance
      response and assessments of working memory in a Y-maze, was also found in 12
      month-old mice. These results suggest that GT-catechin intake partially improves
      the morphologic and functional alterations that occur naturally in the brains of
      aged SAMP10 mice.

PMID- 15236763
TI  - Age-dependent differences in the efficacy of cancer immunotherapy in C57BL and
      AKR mouse strains.
AB  - While tumor incidence increases with age, tumor growth and metastasis often
      proceed at a slower rate in aged organisms. The mechanisms underlying this age
      related reduced tumor development may suggest therapeutic modalities appropriate
      for the aged. Decreased tumor aggressiveness in the old was shown to be related
      to altered immune response. Consequently, the aim of the present study was to
      assess whether cancer immunotherapy has an age-dependent effect. Only a few
      studies have compared cancer immunotherapy efficiency as a function of age, most
      showing lower inhibition in older animals. In the present study, we tested the
      effect of two immunomodulators, levamisole and BCG, on two tumors, B16 melanoma
      and AKR lymphoma, in mice of different ages. We demonstrated a higher efficiency
      of immunotherapy in aged as compared to young mice, particularly at low
      immunomodulator doses. While decreased T cell function during aging is apparently
      established, nonspecific immunity is more preserved or even enhanced in later
      life. We found an increased number of macrophages in tumors of old compared to
      young mice and an increase in MAC-1+ cells in old levamisole-treated compared to
      non-treated mice. The stronger therapeutic effect of this immunomodulator in old
      mice might thus be due to an increased macrophage-mediated anti-tumoral effect.

PMID- 15236764
TI  - Circulating adiponectin levels increase in rats on caloric restriction: the
      potential for insulin sensitization.
AB  - Caloric restriction (CR) has a well-known insulin sensitizing effect in vivo.
      Although this effect has been confirmed in rodents and primates for many years,
      its precise molecular mechanisms remain unknown. Here we show a significant
      increase in plasma adiponectin and a decrease in blood glucose, plasma
      triglyceride and insulin levels in rats maintained on CR diet for 2, 10, 15, and
      20 months. Long-term CR rats exhibited significantly higher insulin-stimulated
      insulin receptor tyrosine phosphorylation and lower PTP-1B activity both in liver
      and skeletal muscle than those observed in rats fed ad libitum (AL). In addition,
      the triglyceride levels in these tissues were significantly lower in long-term CR
      animals. Interestingly, concentrations of plasma adiponectin in long-term CR rats
      were associated with increased expression of the transcription factor mRNAs for
      the peroxisome proliferator-activated receptor (PPAR)alpha, gamma and delta, but
      decreased expression for SREBP-1c, resulting in a concerted modulation in the
      expression of key transcription target genes involved in fatty acid oxidation and
      energy combustion in liver. Taken together, our findings suggest an important
      role for adiponectin in the beneficial effects of long-term CR.

PMID- 15236765
TI  - Anti-aging effects of anti-lipolytic drugs.
AB  - Genetic disruption of insulin and insulin-like signaling pathways may extend
      lifespan. Hyperinsulinemia and insulin resistance may accelerate aging. The
      hypothesis was tested that a once-a-week life-long inhibition of insulin
      secretion by the administration of anti-lipolytic drugs might have anti-aging
      effects. Groups of 3-month-old male Sprague-Dawley rats were (a) given standard
      laboratory food ad libitum (AL); (b) fed AL 6 days and fasted 1 day every week
      (FW); (c) fed AL every other day (EOD), (d) fed like FW and given Acipimox (50
      mg/kg b.w.) on the day of fasting (FWA) by the gastric tube. The AL, FW and EOD
      groups received saline intragastrically. Treatment with ACIPIMOX transiently
      decreased plasma free fatty acids, glucose and insulin and increased valine
      plasma levels, and had no long-term effect on food consumption and body weight.
      By age 6, 12 and 24 months subgroups were taken and the age-related changes in
      liver dolichol and autophagic proteolysis--which are correlated with life
      expectancy--were measured. Liver dolichol levels increased and autophagic
      proteolysis decreased in mature and older AL rats; EOD and FWA fully counteracted
      these changes; FW rats had significant but smaller beneficial effects. It is
      concluded that life-long weekly-repeated transient inhibition of insulin
      secretion by antilipolytic drugs may have an anti-aging effect, additive to the
      anti-aging effect of a milder caloric restriction. Speculation is that
      transiently lower plasma insulin levels might stimulate the anti-aging cell
      repair mechanism autophagy, which has longer lasting effects on cell
      housekeeping.

PMID- 15236766
TI  - Functional and chromosomal clustering of genes responsive to 5-bromodeoxyuridine
      in human cells.
AB  - 5-Bromodeoxyuridine immediately and dramatically induces senescence-associated
      genes in human cells. We examined changes in gene expression in HeLa cells using
      cDNA microarrays containing ca. 39,000 human genes or ESTs. Addition of 5
      bromodeoxyuridine for 4 days changed expression of 2.6% of them twice more (1.5%)
      or less (1.1%) than control levels. We functionally categorized 191 genes that
      showed greater than four times increase or decrease, and found that they have a
      various function. These genes were assigned to various human chromosomes, and
      half of them seemed to cluster at a few regions on individual chromosomes. These
      results suggest that multiple genes collectively act to induce cellular
      senescence and chromatin structure has a role in expression of the genes.

PMID- 15236767
TI  - Alterations of senescence biomarkers in human cells by exposure to CrVI in vivo
      and in vitro.
AB  - Heavy metals like CrVI, CdII, PbII and SnII have many applications in industry.
      They also represent a group of labour pollutants, as they are involved in several
      physiological disorders, such as carcinogenesis and various tissue dysfunctions.
      However, limited knowledge exists regarding their effects on ageing. In the
      current work we provide evidence that workers chronically exposed to CrVI have
      considerably reduced serum levels of the biomarker of senescence and cell
      survival, Apolipoprotein J/Clusterin (ApoJ/CLU). Moreover, we have found that
      both the degree and the time of exposure to CrVI associate negatively with
      ApoJ/CLU serum levels. To further examine whether CrVI directly affects cellular
      senescence we treated for 10 weeks two adult skin fibroblasts cultures as well as
      embryonic fibroblasts with a range of CrVI concentrations that approximate the
      values recorded in the blood circulation of exposed workers. Cellular treatment
      with a CrVI concentration that approximates the highest concentration in the
      blood was extremely toxic and nearly all cells died immediately after the first
      treatment. Interestingly, continuous treatment with a 10-fold lower CrVI
      concentration resulted in the induction of premature senescence. More
      specifically, treated cells were growth arrested, acquired an irregular shape,
      were positive to beta-galactosidase staining, accumulated oxidized proteins and
      over-expressed the cyclin-dependent kinase inhibitor p21 and ApoJ/CLU. Similar
      treatments with three additional labour pollutants resulted in the induction of
      premature senescence by CdII, but not by SnII or PbII. In summary, our results
      indicate that exposure to CrVI induces alterations of senescence biomarkers both
      in vivo and in vitro. They also provide new valuable tools for monitoring CrVI
      cytotoxic effects in vivo as well as for re-evaluating the maximum permissive
      values of some labour pollutants, like CrVI and CdII.

PMID- 15236768
TI  - Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism,
      PON1 activity and HDL levels in healthy Sicilian octogenarians.
AB  - Age is associated with an enhanced low density lipoprotein (LDL) oxidation and
      atherosclerosis, thus, subjects over 80 years without cardiovascular disease
      provide a model to investigate the protective factors against atherosclerosis.
      Serum paraoxonase (PON1), an high density lipoprotein (HDL)-bound enzyme,
      prevents LDL oxidation. The aim of the present study was to evaluate the
      contribution of the PON1 promoter T(-107)C and coding region Gln192Arg (Q192R)
      and Leu55Met (L55M) polymorphisms to the resistance to develop cardiovascular
      events in Sicilian healthy octogenarians. Distribution of PON1 genotypes and
      activity, and biochemical parameters, were compared between 100 octogenarians and
      200 adults. Individuals in the elderly group displayed significant higher levels
      of HDL-C (P < 0.001) and PON1 activity (P < 0.001). The analysis of PON1
      genotypes distribution showed an higher percentage of (-107)CC among
      octogenarians compared with controls. A significant difference among T(-107)C
      genotypes respect to PON1 activity and HDL-C levels occurred in both groups. The
      CC genotype was associated with higher PON1 activity and HDL levels compared to
      the TT genotypes. In conclusion, our results provide a strong evidence that in
      healthy Sicilians ageing may be characterized by a low frequency of PON1 (-107)T
      'risk' allele and by an high frequency of favourable genotypes such as (-107)CC,
      influencing PON1 activity and HDL-C levels.

PMID- 15236769
TI  - Gender specific association of genetic variation in peroxisome proliferator
      activated receptor (PPAR)gamma-2 with longevity.
AB  - Long-lived subjects have been shown to have peculiar anthropometric features
      (i.e. lower body mass index (BMI)) and metabolic parameters (i.e. improved
      insulin sensitivity). Life style and a genetic background potentially protective
      against the age-related metabolic derangement might contribute to such a
      particular phenotype. Peroxisome proliferator-activated receptor (PPAR)gamma-2 is
      an important regulator of adipose tissue metabolism, insulin sensitivity and
      inflammatory response. Thus, the potential role of genetic variability at Pro/Ala
      loci of PPARG gene on longevity was studied in 222 long-lived subjects and 250
      aged subjects. We found a different Pro/Ala genotype frequency distribution
      between long-lived and aged men subjects, long-lived men having an increased
      frequency of Pro/Ala genotype (20 vs 8.5%); no differences was found when allele
      and genotype distribution of Pro/Ala gene polymorphism were analyzed in the two
      age group of women. Interestingly, subjects with Pro/Ala polymorphism had
      significantly lower BMI than Ala/Ala and Pro/Pro polymorphism. In conclusion, our
      study demonstrated that paraoxonase Pro/Ala gene polyporphism is associated with
      human longevity. Such an effect is probably due to the effect of Pro/Ala
      polymorphism on body composition and appears to be gender specific.

PMID- 15236770
TI  - A polymorphic marker in the first intron of the Werner gene associates with
      cognitive function in aged Danish twins.
AB  - Werner's syndrome is a premature aging syndrome with many features common to
      normal aging. The possible association between phenotypic markers for normal
      aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins
      age 70-90 years. All participants were scored every second year using a number of
      physical and cognitive tests. In addition their self-rated health was registered
      as well as self reported status with regards to nine diseases. Blood was drawn
      from all participants and purified DNA was typed for four SNP's in the WRN gene.
      The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an
      unpaired analysis of this material a significant association between the intron 1
      SNP and cognitive function was demonstrated. Our finding, which will need
      corroboration in independent samples, therefore may suggest that the t-allele of
      the intron 1 SNP is beneficial to cognitive function. However, since the t-allele
      of this SNP is very rare, we did not encounter any tt-homozygous individuals for
      this allele.

PMID- 15236771
TI  - Interleukin 6-174 G/C promoter gene polymorphism in centenarians: no evidence of
      association with human longevity or interaction with apolipoprotein E alleles.
AB  - The C allele at position -174 in the promoter of the interleukin 6 (IL-6) gene
      has been associated with reduced gene expression and reduced plasma levels of IL
      6. Given that IL-6 tracks with functional disability and age-related diseases,
      there may be attrition or reduction in the frequency of the homozygous subjects,
      who produce higher IL-6 serum levels, in older survivors in a population. In
      fact, a marked reduction of the IL-6*G/*G genotype was recently demonstrated in
      male though not female Italian centenarians compared with younger age groups.
      First aim of the present study was to investigate whether there was evidence of
      an association among IL-6 -174 G/C promoter polymorphism and extreme longevity in
      a population of 81 centenarians compared with a control group of 122 middle-aged
      healthy subjects (mean age: 51+/-18 SD; range: 19-73 years), from Apulia
      (Southern Italy). Secondly, we also tested possible interaction of apolipoprotein
      E (APOE) alleles with the IL-6 -174 G/C promoter polymorphism in view of our
      recent findings for reduced APOE epsilon4 allele in centenarians. No differences
      have been found in the IL-6 -174 G/C promoter allele and genotype frequencies
      between centenarians and controls nor was there any observed interaction with
      APOE alleles that are also reputed to be linked to longevity. Regional genetic
      differences in conjunction with differing environmental factors may explain in
      part previous results suggesting a role of this polymorphism in longevity.

PMID- 15236772
TI  - Conflicts of interest in medical science: peer usage, peer review and 'CoI
      consultancy'.
AB  - In recent years, the perception has grown that conflicts of interest are having a
      detrimental effect on medical science as it influences health policy and clinical
      practice, leading medical journals to enforce self-declaration of potential
      biases in the attempt to counteract or compensate for the problem. Conflict of
      interest (CoI) declarations have traditionally been considered inappropriate in
      pure science since its evaluation systems themselves constitute a mechanism for
      eliminating the effect of individual biases. Pure science is primarily evaluated
      by 'peer usage', in which scientific information is 'replicated' by being
      incorporated in the work of other scientists, and tested by further observation
      of the natural world. Over the long-term, the process works because significant
      biases impair the quality of science, and bad science tends to be neglected or
      refuted. However, scientific evaluation operates slowly over years and decades,
      and only a small proportion of published work is ever actually evaluated. But
      most of modern medical science no longer conforms to the model of pure science,
      and may instead be conceptualized as a system of 'applied' science having
      different aims and evaluation processes. The aim of applied medical science is to
      solve pre-specified problems, and to provide scientific information ready for
      implementation immediately following publication. The primary evaluation process
      of applied science is peer review, not peer usage. Peer review is much more rapid
      (with a timescale of weeks or months) and cheaper than peer usage and
      (consequently) has a much wider application: peer review is a prospective
      validation while peer usage is retrospective. Since applied science consists of
      incremental advances on existing knowledge achieved using established techniques,
      its results can usually be reliably evaluated by peer review. However, despite
      its considerable convenience, peer review has significant limitations related to
      its reliance on opinion. One major limitation of peer review has proved to be its
      inability to deal with conflicts of interest, especially in a 'big science'
      context when prestigious scientists may have similar biases, and conflicts of
      interest are widely shared among peer reviewers. When applied medical science has
      been later checked against the slower but more valid processes of peer usage, it
      seems that reliance on peer review may allow damaging distortions to become
      'locked-in' to clinical practice and health policy for considerable periods.
      Scientific progress is generally underpinned by increasing specialization.
      Medical journals should specialize in the communication of scientific
      information, and they have neither the resources nor the motivation to
      investigate and measure conflicts of interest. Effectively dealing with the
      problem of conflicts of interest in applied medical science firstly requires a
      more explicit demarcation between the communications media of pure medical
      science and applied medical science. Greater specialization of these activities
      would then allow distinctive aims and evaluation systems to evolve with the
      expectation of improved performance in both pure and applied systems. In future,
      applied medical science should operate with an assumption of bias, with the onus
      of proof on applied medical scientists to facilitate the 'data transparency'
      necessary to validate their research. Journals of applied medical science will
      probably require more rigorous processes of peer review than at present, since
      their publications are intended to be ready for implementation. But since peer
      review does not adequately filter-out conflicts of interest in applied medical
      science, there is a need for the evolution of specialist post-publication
      institutional mechanisms. The suggested solution is to encourage the
      establishment of independent 'CoI consultancy' services, whose role would be to
      evaluate conflicts of interest and other biases in published applied medical
      science prior to their implementation. Such services would be paid-for by the
      groups who intend to implement applied medical research.

PMID- 15236773
TI  - Are cannabinoid drugs neurotoxic or neuroprotective?
AB  - Chronic exposure to cannabinoids was shown to induce long lasting impairment of
      learning and memory, which was accompanied by morphological damage to the brain.
      On the other hand, several studies have shown that cannabinoids can protect from
      various brain traumas. This enigmatic dualism is explained herein by a
      comprehensive hypothesis, which is based on our recent in vitro studies and on
      pharmacokinetic in vivo considerations. The hypothesis predicts that low
      concentrations of cannabinoids will be neurotoxic while high concentrations of
      the drugs will protect from neuronal damage, and suggests that chronic
      administration of cannabinoids will induce neuronal death, while their acute
      administration will protect the brain. We further propose straight forward
      experiments, both in vivo (animal models for brain damage) and in vitro (cell
      death in neuronal cultures) to verify this hypothesis. The outcome of these
      experiments may have practical applications when considering the use of
      cannabinoids as therapeutic agents and in evaluating the consequences of their
      use as recreational drugs.

PMID- 15236774
TI  - Dust mites living in human lungs--the cause of asthma?
AB  - Asthma does not have a clear cause and may represent a cluster of diseases. We
      propose that asthma in house dust mite sensitive patients may be caused by
      recurrent inhalation of live dust mites which are able to live for some time in
      the bronchioles of the lung. To provide themselves with a food source, the mites
      may purposefully excrete proteolytic enzymes, including Der p1, which increase
      epithelial shedding by freeing cells from the basement membrane. The mites then
      feed on the shed respiratory epithelial cells. Consequent loss of an intact
      respiratory epithelium exposes underlying tissues to dust mite protein and other
      allergens triggering sensitisation to these proteins. Later, repeated infestation
      provokes an allergic response which manifests itself as asthma attacks. The
      evidence for this hypothesis was tested against the Bradford-Hill criteria for
      causation; consistency, strength, temporal association and dose response.
      Potential areas for further research were also identified. The association
      between asthmatic symptoms and pulmonary acariasis was consistent across a number
      of studies. Determining the strength of the association and any dose response
      requires more work which is dependent on the development of better tests for the
      detection of mites in sputum. There was tentative evidence of a temporal
      association in the published studies identified. Biological plausibility and
      experimental evidence was available for pulmonary acariasis in primates and
      arsenic treatment was effective in humans. Better tests for mites in sputum are
      needed, as is work to assess more modern anti-acaricidal drugs in dust mite
      sensitive asthmatics.

PMID- 15236775
TI  - A comparative study of age-related brain pathology--are neurodegenerative
      diseases present in nonhuman animals ?
AB  - Although some aged dogs definitely have dementia-like conditions, they have
      rather different brain histopathology from that seen in Alzheimer's disease
      including the shape of senile plaques, severity of neuron loss and absence of
      neurofibrillary tangles. Aged wild-type mice never show such brain lesions at
      all. In addition, no cases of Parkinson's disease have been reported in nonhuman
      animals yet. The reason for this might be non-parallel aging of the whole body
      and brain. If such nonhuman animals had a longer life span, like humans, typical
      Alzheimer's and Parkinson's lesions would be formed in the brain. As the rate of
      deposition of the misfolded proteins causing the lesions might be slow, nonhuman
      animals normally die before the lesions appear.

PMID- 15236776
TI  - Sleep protects excitatory cortical circuits against oxidative damage.
AB  - Activity in excitatory cortical pathways increases the oxidative metabolism of
      the brain and the risk of oxidative damage. Oxyradicals formed during periods of
      activity are mopped up by neural pools of nuclear factor kappa-B resulting in
      their activation and translocation to cell nuclei. During waking hours,
      glucocorticoids inhibit transactivation by nuclear factor kappa-B, increase
      central norepinephrine release, and elevate expression of prostaglandin D2. The
      build-up of nuclear factor kappa-B and prostaglandin D2 produces sleep pressures
      leading to sleep onset, normally gated by circadian melatonin release. During
      slow wave sleep nuclear factor kappa-B induces transcription of synaptogenic and
      antioxidant products and synaptic remodeling follows. Synaptically remodeled
      neural circuits have modified conductivity patterns and timescales and need to be
      resynchronized with existing unmodified neural circuits. The resynchronization
      process, mediated by theta rhythm, occurs during rapid eye movement sleep and is
      orchestrated from pontine centers. Resynchronization of remodeled neural circuits
      produces dreams. The waking state results upon successful resynchronization.
      Rapid eye movement sleep deprivation results in a lack of resynchronization and
      leads to cognitive inefficiencies. The model presented here proposes that the
      primary purpose of sleep is to protect cortical circuits against oxidative damage
      by reducing cortical activity and by remodeling and resynchronizing cortical
      circuits during this period of reduced activity to sustain new patterns of
      activation more effectively.

PMID- 15236777
TI  - High infectious burden, low cancer incidence, and early malignancy in developing
      countries: a molecular hypothesis in term of the role of nitric oxide.
AB  - Nitric oxide (NO) is a neurotransmitter which plays a powerful role in the immune
      system: it kills bacteria, and, it also destroys the tumor cells. Specifically,
      immune system stimuli gamma interferon and lipopolysaccharide transmit signals to
      a macrophage nucleus causing the production of nitric oxide synthase, the enzyme
      that converts arginine to NO. The NO thus produced not only destroys bacteria but
      also attacks the tumor cells by inhibiting the energy-producing Krebs cycle,
      electron transport activity and DNA synthesis. People in developing countries who
      survive repeated childhood infections must be inferred to have robust
      microphage/NO systems and thus, also, a strong immunity against cancer--thence
      the low incidence of cancers in these countries. However, those unfortunate few
      in these countries who do develop cancer, despite a robust microphage/NO system,
      must be presumed to have a markedly virulent tumor development micro-environment
      (e.g., activation of tumor promotion genes, inactivation of tumor suppression
      genes, multiple mutations, etc.) that escapes even the particularly alert immune
      surveillance--thence the earlier (by about a decade) death by cancer in those
      countries. Thus the NO hypothesis put forward here simultaneously provides a
      mechanistic causation for (i) low cancer incidence in countries subjected to
      heavy infectious burdens, and (ii) the earlier occurrence (by about a decade) of
      major cancers in those countries when the immune surveillance, despite its
      robustness, fails to destroy the incipient formation of cancer cells.

PMID- 15236778
TI  - Elevated silver, barium and strontium in antlers, vegetation and soils sourced
      from CWD cluster areas: do Ag/Ba/Sr piezoelectric crystals represent the
      transmissible pathogenic agent in TSEs?
AB  - High levels of Silver (Ag), Barium (Ba) and Strontium (Sr) and low levels of
      copper (Cu) have been measured in the antlers, soils and pastures of the deer
      that are thriving in the chronic wasting disease (CWD) cluster zones in North
      America in relation to the areas where CWD and other transmissible spongiform
      encephalopathies (TSEs) have not been reported. The elevations of Ag, Ba and Sr
      were thought to originate from both natural geochemical and artificial pollutant
      sources--stemming from the common practise of aerial spraying with 'cloud
      seeding' Ag or Ba crystal nuclei for rain making in these drought prone areas of
      North America, the atmospheric spraying with Ba based aerosols for
      enhancing/refracting radar and radio signal communications as well as the
      spreading of waste Ba drilling mud from the local oil/gas well industry across
      pastureland. These metals have subsequently bioconcentrated up the foodchain and
      into the mammals who are dependent upon the local Cu deficient ecosystems. A dual
      eco-prerequisite theory is proposed on the aetiology of TSEs which is based upon
      an Ag, Ba, Sr or Mn replacement binding at the vacant Cu/Zn domains on the
      cellular prion protein (PrP)/sulphated proteoglycan molecules which impairs the
      capacities of the brain to protect itself against incoming shockbursts of sound
      and light energy. Ag/Ba/Sr chelation of free sulphur within the biosystem
      inhibits the viable synthesis of the sulphur dependent proteoglycans, which
      results in the overall collapse of the Cu mediated conduction of electric signals
      along the PrP-proteoglycan signalling pathways; ultimately disrupting GABA type
      inhibitory currents at the synapses/end plates of the auditory/circadian
      regulated circuitry, as well as disrupting proteoglycan co-regulation of the
      growth factor signalling systems which maintain the structural integrity of the
      nervous system. The resulting Ag, Ba, Sr or Mn based compounds seed piezoelectric
      crystals which incorporate PrP and ferritin into their structure. These
      ferrimagnetically ordered crystals multireplicate and choke up the PrP
      proteoglycan conduits of electrical conduction throughout the CNS. The second
      stage of pathogenesis comes into play when the pressure energy from incoming
      shock bursts of low frequency acoustic waves from low fly jets, explosions,
      earthquakes, etc. (a key eco-characteristic of TSE cluster environments) are
      absorbed by the rogue 'piezoelectric' crystals, which duly convert the mechanical
      pressure energy into an electrical energy which accumulates in the crystal-PrP
      ferritin aggregates (the fibrils) until a point of 'saturation polarization' is
      reached. Magnetic fields are generated on the crystal surface, which initiate
      chain reactions of deleterious free radical mediated spongiform neurodegeneration
      in surrounding tissues. Since Ag, Ba, Sr or Mn based piezoelectric crystals are
      heat resistant and carry a magnetic field inducing pathogenic capacity, it is
      proposed that these ferroelectric crystal pollutants represent the transmissible,
      pathogenic agents that initiate TSE.

PMID- 15236779
TI  - Is there an association between multiple myeloma and prostate cancer?
AB  - In a series of 700 consecutive patients with prostate cancer, four patients were
      noted to have a history of multiple myeloma. An association between prostate
      cancer and multiple myeloma had not been previously described. An exploratory
      investigation of the biological basis of these two malignancies was undertaken to
      determine a possible mechanism for this association. A review of the genetic,
      molecular and chemical basis of prostate cancer and multiple myeloma development
      and progression is presented. A model suggesting the possible impact of
      immunosuppression from multiple myeloma and chemokines released by circulating
      myeloma cells including IGF-1, IL6, SDF1 and VEGF on the progression of prostate
      cancer to detectable stages is presented.

PMID- 15236780
TI  - Transcriptional homeostasis: a mechanism of protein quality control.
AB  - Sickle cell anaemia confirms that minor mutations in protein sequence can have
      catastrophic effects. However, RNA transcription depends on polymerases that have
      low fidelity and introduce errors at a rate of 10(-5) substitutions/base
      synthesised. For many large proteins translation of these errors could result in
      significant loss of function, while for others (for example, cell surface
      signalling proteins) variability of protein expression could be advantageous.
      This paper outlines a mechanism that enables proteins to modulate error
      incorporation (variability) into RNAs sysnthesised by RNA polymerase-
      transcriptional homeostasis--thereby modulating, and error correcting, their own
      sysnthesis. Transcriptional homeostasis is a fundamental regulatory mechanism
      relevant to control of gene expression.

PMID- 15236781
TI  - Are phospholipid-binding antibodies implicated in the pathogenesis of diabetic
      microangiopathy?
AB  - Diabetic retinopathy (DR) is a major cause of blindness in the working population
      of the Western world and there is no doubt that its prevalence is strongly
      related to the duration of diabetes and the glycemic control. However, although
      intensive diabetes management, with the goal of achieving near-normal glycemia,
      has been shown to prevent and/or delay the onset of DR, there is now ample of
      evidence that the development of this microangiopathy is a multifactorial process
      in which genetic, metabolic, haemostatic and growth factors play an important
      role. Moreover, given the suggestions that immunological mechanisms might have a
      role in the pathogenesis of diabetic microangiopathy via immune complex
      deposition, it has been hypothesized that antiphospholipid antibodies (A-Ab)
      directed against endothelial antigens could be responsible for initiating
      vascular injury. In particular, not only A-Ab production was found to be
      increased in patients with overt nephropathy or macroangiopathy but also Lupus
      Anticoagulant positivity, representing an intersection point between immune and
      haemostatic alterations, has been highlighted as a potential and additional risk
      factor in the pathogenesis of microangiopathy in type 1 diabetics. Moreover,
      given the high levels of activated protein C, endothelin-1 and thrombo-modulin
      that have been observed in normo-albuminuric and uncomplicated patients, it has
      been concluded that the vascular endothelium shifts pathologically from an
      antithrombotic to a prothrombotic state even in the early phases of the disease.
      This condition was found to be more pronounced in subjects with anticardiolipin
      positivity and/or high circulating immune complexes concentrations, since they
      possess the ability not only to induce platelet activation and aggregation but
      also to activate the complement system via the classical pathway. Therefore, a
      potential synergism between generation of autoantibodies, haemostatic alterations
      and endothelial stress has been suggested, a stimulating hypothesis that needs
      further studies to be clarified in its complexity.

PMID- 15236782
TI  - Hyperuricaemia and preeclampsia: is there a pathogenic link?
AB  - OBJECTIVE: A hypothesis, based on animal studies and human observational studies,
      was developed proposing a direct pathogenic link between hyperuricemia and
      preeclampsia. Epidemiological characteristics of preeclampsia such as its
      uniqueness to humans and an increased incidence of preeclampsia in multiple
      pregnancies, increased body mass index, renal and hypertensive disease all have
      uric acid as their common denominator. Animal studies have linked hyperuricaemia
      to hypertensive, cardiovascular and renal disease. The aim of the study was to
      determine whether lowering the serum uric acid levels in preeclampsia would
      affect biochemical parameters and hypertensive control. DESIGN: A randomized,
      double-blind, placebo controlled study. SETTING: A tertiary referral center.
      POPULATION: Forty women with preeclampsia between 26 and 32 weeks gestation.
      INTERVENTION: Probenecid 250 mg twice daily for seven days. MAIN OUTCOME
      MEASURES: Renal function and haematological parameters, hypertensive control.
      RESULTS: In the Probenecid group, there was a significant drop in the serum uric
      acid levels. Lower uric acid levels in the Probenecid group had no significant
      effect on blood pressure. Patients in the Probenecid group had a significantly
      lower serum creatinine value at the end of the study when compared to patients in
      the placebo group. Other renal function parameters (creatinine clearance, urea,
      24 h urinary protein excretion) did not show any significant difference between
      the two groups. Platelet count differed between the two groups with the platelet
      count being significantly higher in the Probenecid group at the end of the study.
      CONCLUSION: The significant improvement in the platelet count in the Probenecid
      group warrants further study.

PMID- 15236783
TI  - Ionotropic glutamate receptor activated by N-methyl-D-aspartate: a key molecule
      of conscious life.
AB  - We want to propose that basic stereotyped integrative functions are the result of
      sequentially built neuronal circuits in the primitive regions of the brain in
      whose build-up a particular subunit composition iGluR-NMDA would play a central
      role. iGluR-NMDA is a multiregulated heteromeric glutamate receptor-ion channel
      found in plasma membranes of neurons and other cells. iGluR-NMDA may be composed
      of up to five subunits, depending on the type of cell involved and its location.
      There are three major types of subunits and there are variations within each type
      allowing for up to 13 possible subunits, at least in the rat, which differ from
      each other in amino acid sequence and thus, in tertiary structure. The actual
      iGluR-NMDA heteropolymer involved in a given function may thus have a great
      number of subunit composition possibilities which would be the result of the
      particular genes expressed in a given type of cell. The iGluR-NMDA is an ion
      channel that opens in response to glutamate in a highly regulated fashion in
      which different molecules and ions present in the interstitial fluid determine
      whether or not the channel opens upon glutamate binding. The original function of
      iGluR-NMDA may have been that of allowing calcium influx to cells. As the brain
      receives external stimuli through the senses, new circuits will be formed
      stepwise in the neocortex in which a particular subunit composition iGluR-NMDA
      will be involved. Differentiation between external stimuli generated circuits and
      those governing internal functions will allow distinction between self and non
      self, thus generating conscious awareness. The role of the particular subunit
      composition iGluR-NMDA proposed would be that of providing a means of calcium
      influx to the synapses to be formed and, if the same stimulus is forthcoming,
      allowing permanent synapses formation through the membrane incorporation of
      calcium dependent adhesion molecules such as cadherins and cytoskeleton
      reorganization promoted by nectins.

PMID- 15236784
TI  - 1alpha,25-dihydroxy-vitamin-D3 as new immunotherapy in treatment of recurrent
      spontaneous abortion.
AB  - Recurrent spontaneous abortion (RSA) is serious health problem affecting 2-5% of
      reproducing couples worldwide. It has long been suspected that nearly 80% of the
      unexplained RSAs are due to immunologic causes. Although the major tissue
      confronting the mother's immune system is the placental villous trophoblast, the
      immunological risk to the developing embryo is not great until the time of
      implantation. In addition, trophoblast is not sensible to lysis by NK cells, TNF
      alpha or macrophages, but may be killed by lymphokine activated NK cells (LAK)
      and may undergo apoptosis in response to TNF-alpha and/or IFN-gamma in vitro. The
      two most commonly used treatments for RSA are intravenous immunoglobulin (IVIg)
      and alloimmunization with partner's leukocytes (LIT). We promote vitamin D3 as
      new immunomodulatory agent in treatment of RSA. Different mechanisms have been
      proposed to account for the immunosuppressive effect of 1alpha, 25-dihydroxy
      vitamin-D3 (VD3). Portion of the VD3 activity involves the downregulation of IL
      2, IFN-gamma and TNF-alpha genes transcription. Because immunomodulatory effects
      of VD3 are very similar to IL-10 effects, acting of VD3 in immunotherapy of RSA
      syndrome, preeclamptic and eclamptic pregnancy, as well as PIH syndrome, is very
      reasonable. We propose using of VD3 as immunotherapy or adjuvant therapy in
      combination with classic immunotherapies of endangered pregnancies.

PMID- 15236785
TI  - Limitations on the cloning of humans and other mammals.
AB  - The nature of clones is discussed along with the origin and principles of the
      concept that human and other mammalian clones can be produced. The physical and
      chemical properties of living cells are described and it is shown these
      properties place severe limitations on attempts to bring human and mammalian
      clones into being. The observed result of such attempts that a large number of
      distorted and aborted foetii have been produced is demonstrated to have been
      predictable. Offspring produced by such attempts cannot be classified under any
      of the normal classifications of human relationships e.g. son, daughter, brother,
      sister or twin and that such offspring are entirely unnatural and likely to be
      metabolically unstable. It is concluded that the cloning of humans and other
      mammals is difficult, certainly dangerous and perhaps impossible.

PMID- 15236786
TI  - Analysis of the threshold liability model provides new understanding of causation
      in autoimmune diseases.
AB  - Autoimmune diseases include a heterogeneous group of complex traits, the causes
      of which are essentially unknown. The threshold liability model is a hypothesis
      that has a significant influence on thinking about causation in these diseases.
      Here, I analyze this model and assess its utility in understanding causation in
      autoimmunity. According to the model, members of a population have a normal
      distribution of genetic liability for a particular autoimmune disease. Further, a
      threshold value exists for each autoimmune disease such that an individual
      develops disease when his/her liability exceeds the threshold value;
      environmental and stochastic factors and epistatic gene interactions may increase
      or decrease an individual's disease liability. There are, however, two main
      problems with the threshold liability model. First, for a particular autoimmune
      disease, the threshold value divides a population into two distinct groups that
      consist either of affected or of healthy individuals. I show that this
      dichotomous division is inaccurate and misleading. Second, the threshold value
      corresponds to the occurrence of a component-cause of disease, i.e. when an
      appropriate collection of causative factors for a particular autoimmune disease
      is present, the disease must inevitably occur. I argue, however, that the disease
      contribution of essentially unknown random or stochastic factors to causation is
      at least similar in importance to the contributions of genetic and environmental
      factors. These stochastic factors add a significant element of unpredictability
      to the effects of genetic and environmental factors. Consequently causes in
      autoimmunity do not act deterministically, which is implied by the component
      cause concept. Instead, the role of causative factors is to alter disease risk. I
      therefore reject the threshold liability model and conclude that a probabilistic
      approach provides the only reasonable way to understand causation in autoimmune
      diseases. This conclusion has important implications for other deterministic
      hypotheses in autoimmunity including other component-cause hypotheses.

PMID- 15236787
TI  - Phosphate depletion is the link between growth, stress and diet in the aetiology
      of MS.
AB  - Predisposition to multiple sclerosis (MS) can originate in adolescence, when
      nutrient requirement is high and not satisfied and because of too little food
      intake and/or a poor diet. Growth per se increases the need for phosphate, an
      often neglected mineral in clinical conditions. The combination of marginal
      nutrition (either under- or malnutrition) with a negative phosphate balance,
      physical exertion, infections or other types of stress during puberty can disturb
      metabolism and result in demyelinization. Phosphate depletion (PD) can lead to
      neurological complications, which have been characterized in experimental and
      clinical studies. Hypophosphataemia, whether acute or chronic, induced by stress
      from accident, surgery or burns, by infection and/or undernutrition, is therefore
      an important etiological factor. Low SP levels have been reported in MS patients
      and the hypothesis that PD causes MS is presented here.

PMID- 15236788
TI  - Do the emotional side-effects of hormonal contraceptives come from pharmacologic
      or psychological mechanisms?
AB  - Hormonal preparations have become one of the most popular methods used for
      controlling fertility. The literature over the last 40 years continues to reveal
      how their numerous side effects negatively impact many users and even society at
      large. Three large cohort trials were the first to demonstrate, on a grand scale,
      certain emotional and behavioral associations with contraceptive use. Current
      contraceptive use was associated with an increase rate in depression, divorce,
      tranquilizer use, sexual dysfunction, and suicide and other violent and
      accidental deaths. Despite the advent of more "user friendly" contraceptives, the
      discontinuation rate secondary to side effects has changed little through the
      years. While in rare cases hormonal preparations can be deadly to the user, there
      is substantial evidence that their negative effect issues more from their
      emotional and behavioral properties. This paper reviews the results of over seven
      studies which further characterize these prominent associations, particularly
      with hormonal contraception, in an attempt to demonstrate their association with
      the intrinsic pharmacologic properties of hormonal preparations. Hormonal
      contraceptive users, in contrast with non users, were found to have higher rates
      of depression, anxiety, fatigue, neurotic symptoms, sexual disturbances,
      compulsion, anger, and negative menstrual effects. The question of whether the
      association of these maladies is directly due to the effect of taking exogenous
      hormones versus the psychological impact of the contraceptive behavior itself had
      yet to be studied. Seven small randomized-controlled trials were found in a
      review of the literature which studied this hypothesis in a direct way. They do
      not support the origination of these side effects being from the pharmacological
      properties of hormones. No association was found between hormone levels and
      emotional functioning in females. Psychiatric evaluations among IUD and oral
      contraceptive pill (OCP) users reveal no significant differences. Women who were
      given an OCP placebo experienced a similar side effect profile of OCP users.
      Different hormonal concentrations and combinations made no significant difference
      in the side effect profile. A study of women who were given either "weak female
      hormones" or a placebo failed to duplicate the side effect profile found in all
      of the other studies where the hormones were labeled as contraceptives. The
      evidence suggests that most of the side effects of hormonal contraception are a
      result of a psychological response to the practice of contraception. More study
      is warranted to further understand this psychological phenomenon, especially now
      that an effective non-contraceptive method of fertility regulation and more
      reliable psychological instruments are available. Furthermore, it is reasonable
      to hypothesize, given the present data, that contraceptive activity itself is
      inherently damaging to women.

PMID- 15236789
TI  - Role of melatonin in carbon monoxide-induced hypoxemia.
AB  - Melatonin (MEL) works in tandem with serotonin (5HT), where an equilibrium exists
      in perfect health. Under stress or in crisis, it may be that the production of
      MEL predominates in conjunction with ever increasing production of reactive
      oxygen species (ROS), may lead to hypoxemia and consequently, to metabolic
      disruption. The Melatonin Hypothesis could offer an explanation towards certain
      clinical observation and may support the Catacholamine Hypothesis in the
      development of depression but it is the role played by carbon monoxide (CO) in
      inducing hypoxemia which may result in the Cascade Effect that could in turn
      explain the development of neurodegenerative, neurodevelopmental as well as
      immune dysfunctional type disorders, prevalent today. CO-induced hypoxemia is an
      important aspect in any discussion of cell integrity as CO is formed endogenously
      from the degradation of erythrocytic heme, any hemolytic disturbance or lipid
      peroxidation, may increase the level in blood. CO, in inducing hypoxemia, causes
      the generation of large quantities of hydroxyl (-OH) which could damage specific
      amino acid and disorder protein metabolism that may result in the creation of
      toxic metabolites. Hydroxyl damage is emerging as the precursor to low-grade
      inflammation in the presence of C Reactive Protein (CRP) that is currently
      speculated in the etiology of many known disorders. As disordered protein
      metabolism may play a crucial role in the formation of the cascade, the
      hypothesis aims to address the issues of cell viability and the process of cell
      replication in the event where cell integrity is severely compromised in the face
      of apoptotic and/or necrotic damage, as the intra-cellular and extra-cellular
      environments are becoming increasingly hostile. Where -OH damage to specific
      amino acid in protein may contribute to the Cascade Effect, the hypothesis goes
      further to explain the importance of the Circardian Cycle and the role of
      paradoxical sleep, by taking into consideration the need for repair and for
      regeneration in order to maintain morphology as any cellular event that depends
      on a redox state is likely to be compromised in an event of hypoxemia. As MEL
      enters a cell readily because of its high lipid solubility, the role of MEL
      becomes clear as in its diversity, MEL is a potent oxygen radical scavenger that
      operates throughout the cell.

PMID- 15236790
TI  - Adjuvant targeted therapy with trastuzumab may decrease metastatic capacity in
      specific group of oropharyngeal cancer patients: downregulation of E-cadherin
      catenin complex by cooperative effect of erbB-2 and human papillomavirus type 16
      E6/E7 protooncogenes.
AB  - Human papillomavirus (HPV) type 16 is causally associated with a subset of oral
      cancers, predominantly those cancers arising in the oropharynx (OP). Increased
      HPV16 E6 and E7 oncogene expressions are responsible for the malignant
      transmission in these cancers. ErbB-2 is the family member most closely
      implicated in human cancer, where it is overexpressed in about 30% of carcinomas
      including head and neck squamous cell carcinoma. Coexpressions of E6/E7 and ErbB
      2 downregulate E-cadherin and catenin expression, therefore induces metastatic
      process. Trastuzumab is a humanized monoclonal antibody that recognizes the ErbB
      2 protein receptor and breakthrough in the treatment of metastatic breast cancer
      in combination with chemotherapeutic agents. This antibody is also in clinical
      testing for adjuvant treatment of breast cancer. We propose that trastuzumab as
      an adjuvant treatment may decrease process of tumor metastasis in oropharyngeal
      cancer patients who completed primary treatment (surgery and/or radiotherapy) and
      show expression of both HPV16 E6/E7 and erbB-2 oncoproteins. In vitro and in vivo
      studies with trastuzumab in these subgroup of patients may support our
      hypothesis.

PMID- 15236791
TI  - Mitoses and cancer.
AB  - Mitoses are coupled to cell proliferation. In non-neoplastic cells they are
      usually symmetric and typical and lead to increase in cell number. Cancer cells
      are notorious for their asymmetric divisions, which are considered to reflect
      abnormalities due to disordered growth. The centrosome controls the mitotic
      activity and it has been proposed that centrosomal defects possibly contribute to
      carcinogenesis and aneuploidy of cancer cells. So far the atypical mitoses often
      seen in neoplastic cells are not considered unique. However careful observation
      of atypical mitoses in various neoplasms revealed that although they were indeed
      "atypical" they resembled each other within the same tumor and were different
      from those of other tumors. It is proposed that specific centrosomal alterations,
      which lead to a limited variety of atypical mitotic figures in each neoplasm, are
      not a random result but a distinct event that is possibly involved in
      carcinogenesis.

PMID- 15236792
TI  - The role of RBC destruction in vascular regions with high turbulence on
      atherosclerosis.
AB  - After intravascular red blood cell (RBC) destruction, released hemoglobin
      exceeding the binding capacities of haptoglobin and hemopexin would contribute,
      as free hemoglobin and/or hemin and/or methemalbumin, to the pathogenesis of
      atherosclerosis. Especially in some regions of vasculature with a high turbulence
      strong enough to destruct fragile or old RBCs, free hemoglobin concentrations can
      exceed locally the binding capacities of haptoglobin and hemopexin although their
      measured venous concentrations are normal. As a very simple model of this
      possible very local event we analysed free hemoglobin and methemalbumin levels
      after blood collection into evacuated tubes, and found that the increase of
      methemalbumin is more significant than free hemoglobin. The measurement of free
      hemoglobin and methemalbumin concentrations of arterial blood samples just from
      pre- and post-atherosclerotic lesions can likely shed new light on our
      understanding of the development of atherosclerosis.

PMID- 15236793
TI  - Brain cholinesterases: I. The clinico-histopathological and biochemical basis of
      Alzheimer's disease.
AB  - Substantial evidence is presented demonstrating that it is the cholinesterases
      (ChEs) that constitute the organizer, the connector and the safeguard for
      multiple neurochemical functions and mature anatomical architecture of the brain.
      In Alzheimer's disease (AD), the histopathological characteristics are initially
      and primarily associated with the degeneration of the acetylcholinesterase (AChE)
      system in various brain regions. Multiple classic and/or putative
      neurotransmitters and neuromodulators, virtually all the peptide hormones of the
      endocrine and neuroendocrine systems in the brain, their specific synthesizing
      and hydrolyzing marker enzymes and associated uptake processes (transporters),
      and receptors, do not actually participate in the formation of senile plaques and
      neurofibrillary tangles in the brains of patients suffering from AD. The massive
      perturbation in different neurochemicals seen in AD is essentially caused by the
      ChEs-associated pathology. The graded patterns of brain ChEs expression affect
      the preferential vulnerability and severity of the AD clinico-pathologic
      presentation. It seems that the common law in nature may also dominate the
      destiny of brain ChEs system, i.e., the weaker the cells express AChE, the more
      susceptible the cells are to AD degeneration, and vice versa.

PMID- 15236794
TI  - Brain cholinesterases: III. Future perspectives of AD research and clinical
      practice.
AB  - Alzheimer's disease (AD) is initially and primarily associated with the
      degeneration and alteration in the metabolism of cholinesterases (ChEs). The use
      of ChEs inhibitors to treat Alzheimer's condition, on the basis of the
      cholinergic hypothesis of the disease, is, therefore, without grounds. Most
      disturbing is the fact that the currently available anti-ChEs are designed to
      inhibit normal ChEs in the brain and throughout the body, but not the abnormal
      ones. Based on the acetylcholinesterase (AChE) deficiency theory, treatment
      should be designed to protect the cranial ChEs system from alteration and/or to
      help that system fight against degeneration through restoring its homeostatic
      action for brain structure and function instead. The overlap in the clinical,
      biochemical, molecular-cellular, and pathological alterations seen in patients
      with AD and individuals with many other brain disorders, which has bewildered
      many investigators, may now be explained by the shared underlying mismetabolism
      of brain ChEs. The abnormal metabolism of ChEs existing in asymptomatic subjects
      may indicate that the system is "at risk" and deserves serious attention. Future
      perspectives of ChEs research in vivo and in vitro in connection with AD and
      clinical diagnosis, prevention and treatment are proposed. Several potentially
      useful therapeutic and preventive means and pharmacological agents in this regard
      are identified and discussed, such as physical and intellectual stimulation, and
      a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline),
      acetyl L-carnitine, cytidine diphosphocholine (CDP-choline), centrophenoxine, L
      phenylalanine, naloxone, galactose, and lithium, that have been proven to be able
      to stimulate AChE activity. Their working mechanisms may be through directly
      changing the configuration of AChE molecules and/or correcting micro- and overall
      environmental biological conditions for ChEs.

PMID- 15236795
TI  - Brain cholinesterases: II. The molecular and cellular basis of Alzheimer's
      disease.
AB  - Currently available evidence demonstrates that cholinesterases (ChEs), owing to
      their powerful enzymatic and non-catalytic actions, unusually strong
      electrostatics, and exceptionally ubiquitous presence and redundancy in their
      capacity as the connector, the organizer and the safeguard of the brain, play
      fundamental role(s) in the well-being of cells, tissues, animal and human lives,
      while they present themselves adequately in quality and quantity. The widespread
      intracellular and extracellular membrane networks of ChEs in the brain are also
      subject to various insults, such as aging, gene anomalies, environmental hazards,
      head trauma, excessive oxidative stress, imbalances and/or deficits of organic
      constituents. The loss and the alteration of ChEs on the outer surface membranous
      network may initiate the formation of extracellular senile plaques and induce an
      outside-in cascade of Alzheimer's disease (AD). The alteration in ChEs on the
      intracellular compartments membranous network may give rise to the development of
      intracellular neurofibrillary tangles and induce an inside-out cascade of AD. The
      abnormal patterns of glycosylation and configuration changes in ChEs may be
      reflecting their impaired metabolism at the molecular and cellular level and
      causing the enzymatic and pharmacodynamical modifications and neurotoxicity
      detected in brain tissue and/or CSF of patients with AD and in specimens in
      laboratory experiments. The inflammatory reactions mainly arising from ChEs
      containing neuroglial cells may facilitate the pathophysiologic process of AD. It
      is proposed that brain ChEs may serve as a central point rallying various
      hypotheses regarding the etio-pathogenesis of AD.

PMID- 15236796
TI  - Leukocyte(s) degranulation: therapeutic targets in [NTP]O and [NDP]O mediated
      leukocyte(s) degranulation.
AB  - Extracellular nucleotide-induced stimulation and activation of peripheral blood
      leukocyte(s) and subsequent degranulation plays a critical role in immediate type
      hypersensitivity reaction and other inflammatory diseases. The extracellular
      nucleotides [NTP]O stimulate a P2Y receptor(s) on human PMN with the
      pharmacological profile similar to that of the P2Y2 receptor. Whereas, [NTP]O and
      [NDP]O, bind to P2Y2 and P2Y1 receptors on mononuclear leukocytes. Based on a
      recent proposal on the molecular mechanism of [NTP]O- and [NDP]O-induced
      leukocyte(s) degranulation, a scheme indicating the therapeutic targets with
      potential avenues for attenuating leukocyte(s) degranulation is suggested.

PMID- 15236797
TI  - Neutrophil degranulation: therapeutic targets in [NTP]O mediated neutrophil
      degranulation.
AB  - Extracellular nucleotide-induced stimulation and activation of peripheral blood
      neutrophil and subsequent degranulation plays a critical role in immediate type
      hypersensitivity reaction and other inflammatory diseases. The extracellular
      nucleotides stimulate a P2Y receptor(s) on human PMN with the pharmacological
      profile similar to that of the P2Y2 receptor. Based on a recent proposal on the
      molecular mechanism of [NTP]O-induced neutrophil degranulation, a scheme
      identifying the therapeutic targets, is suggested with potential avenues for
      attenuating PMN degranulation.

PMID- 15236798
TI  - AMPK activation may suppress hepatic production of C-reactive protein by
      stimulating nitric oxide synthase.
AB  - The utility of C-reactive protein (CRP) as an independent risk factor for
      vascular events may be attributable, at least in part, to a direct adverse impact
      of CRP on endothelial function. In particular, modestly elevated concentrations
      of CRP have been shown to decrease the expression of the endothelial isoform of
      nitric oxide synthase (eNOS) in endothelial cells; the implication of this for
      vascular health is evident. Strategies for decreasing elevated CRP include
      administration of statins, thiazolidinediones, and metformin; moderate alcohol
      consumption and appropriate weight loss are also helpful in this regard.
      Metformin's antidiabetic efficacy is now known to reflect activation of AMP
      activated kinase (AMPK); AMPK can stimulate eNOS, which is expressed in
      hepatocytes. A recent study shows that nitric oxide suppresses the activation of
      Stat3 by interleukin-6 in hepatocytes; Stat3 is crucial for the IL-6-mediated
      induction of CRP and various other acute phase reactants. Thus, it is proposed
      that metformin--or AMPK---inhibits hepatic CRP production by boosting hepatic
      nitric oxide synthesis, which in turn impedes Stat3 activation and CRP
      transcription. This hypothesis should be readily testable in cultured
      hepatocytes. Although the impact of metformin on plasma IL-6 levels has not been
      reported, the possibility that AMPK activation could influence adipocyte
      secretion of this cytokine also merits scrutiny.

PMID- 15236799
TI  - Chronic activation of AMP-activated kinase as a strategy for slowing aging.
AB  - Caloric restriction down-regulates insulin secretion and systemic IGF-I activity,
      and there is reason to suspect that these effects are key mediators of caloric
      restriction's favorable impact on longevity. Alternative strategies for down
      regulating these hormones are thus of great interest; chronic activation of AMP
      activated kinase (AMPK)--clinically achievable with the drug metformin--may have
      utility in this regard. In the liver, AMPK slows hepatic glucose output by down
      regulating expression of glucose-6-phosphatase and phosphoenolpyruvate
      carboxykinase; in skeletal muscle, it boosts the efficiency of insulin-stimulated
      glucose uptake by increasing expression of GLUT-4. These effects evidently
      mandate a down-regulation of insulin secretion. The resulting reduction of
      hepatic insulin activity can be expected to suppress hepatic production of IGF-I
      while boosting that of IGFBP-1, thereby decreasing plasma free IGF-I. AMPK can
      also directly stimulate IGFBP-1 synthesis in hepatocytes, and interfere with the
      ras/raf/erk pathway of IGF-I signaling. In non-diabetics, metformin therapy is
      indeed reported to reduce plasma levels of insulin and of free IGF-I; indeed,
      this is thought to be the mechanism whereby metformin suppresses excess androgen
      production in PCOS. A pro-longevity effect of the related biguanide phenformin
      has already been reported in tumor-prone mice, and mouse longevity studies with
      metformin are currently in progress. The development of AMPK activators which do
      not share metformin's modest risk of inducing lactic acidosis--apparently
      reflecting an inhibition of mitochondrial complex 1 that is not intrinsic to AMPK
      activity--might aid the practical applicability of this pro-longevity strategy.

PMID- 15236800
TI  - Does bitter melon contain an activator of AMP-activated kinase?
AB  - Extracts of the unripe fruit of Momordica charantia--bitter melon, which
      flourishes throughout the tropics--appear to have utility in the management of
      type 2 diabetes. Rodent studies suggest that the thus-far-uncharacterized active
      components of such extracts enhance the efficiency of postprandial glucose
      storage in muscle and liver, and likely diminish excessive hepatic glucose
      output, while often down-regulating serum insulin--effects comparable to those
      reported for metformin. Other parallels between the actions of metformin and
      bitter melon in rodents appear to include: analogous effects on the hepatic
      activity of certain enzymes of glucose metabolism; increased expression of GLUT4
      in the plasma membrane of skeletal muscle; a tendency to prevent weight gain;
      favorable effects on serum lipids; and an anti-promotional impact on cancer
      induction. Inasmuch as the clinical efficacy of metformin has recently been
      traced to its ability to activate AMP-activated kinase, it would be of interest
      to determine whether bitter melon extracts contain activators of this enzyme. The
      fact that bitter melon has the potential to down-regulate insulin suggests that,
      beyond its likely utility in the management of diabetes, it may have preventive
      value with respect to a wide range of disorders in which hyperinsulinemia plays a
      pathogenic role--and possibly could even favorably impact the aging process.

PMID- 15236801
TI  - Modulation of autonomic balance by tumors and viruses.
AB  - Autonomic balance, a function generally under host control, is subject to
      modulation by other signalers. In some cases, modulation of host autonomic
      function through behavioral and physical stressors exerted by another individual
      may have negative consequences for the stress recipient by inducing sympathetic
      bias. Modulation of autonomic function may sometimes benefit one party at the
      expense of another. Tumors and HIV are examples of illegitimate signalers who may
      induce host sympathetic bias to promote their own growth and evade host immune
      surveillance. Paraneoplastic and paraviral syndromes such as hypertrophic
      osteoarthopathy, QTc prolongation, insomnia, and cachexia could be viewed as
      epiphenomena related to the tumoral and viral manipulation of host autonomic
      balance. In a more general framework, other paraneoplastic and paraviral
      syndromes may represent epiphenomena related to modulation of endocrine,
      cytokine, and autonomic functions by tumors and viruses to promote their own
      survival. Spatial distribution of cancers and viruses within the host may reflect
      affinity for strategic locations that facilitate manipulation of a variety of
      host functions including autonomic, endocrine, and cytokine regulation. A more
      general for understanding spatial distribution of diseases based on gradients of
      autonomic balance in the body are explored. Darwinian perspectives are discussed.

PMID- 15236802
TI  - Tumors may modulate host immunity partly through hypoxia-induced sympathetic
      bias.
AB  - Hypoxia can occur in solid tumors when oxygen demand from rapid tumor growth
      outstrips the blood supply. Once thought to be merely a consequence of tumor
      physiology, more recent evidence suggests that hypoxia may also be a tumor
      adaptation to promote its own survival. For example, hypoxic conditions generate
      local transcriptional changes that enhance angiogenesis and glycolysis, processes
      that directly promote tumor growth. We hypothesize that maladaptive local
      chemoreceptor host response to hypoxia may contribute to a shift in immune
      balance that favors cancer survival. Specifically, we propose that hypoxia in the
      tumor microenvironment activates local adrenergic activity which in turn inhibits
      Th1 function while favoring Th2 function. Th1 function is vital to the host
      defense against cancer, and Th1 depletion is associated with increased cancer
      risk. In our view, the sympathetic bias induces Th2 bias independent of the
      direct immunomodulatory effects of tumor-derived cytokines. The hypoxia-induced
      local adrenergic response may be part of a broad tumor adaptation that enables
      its evasion of host immune surveillance. That the host response of Th2 bias is so
      reflexively linked to hypoxia may reflect the likelihood that trauma, rather than
      modern diseases such as cancer, were the most common causes of hypoxia during our
      teleologic past when natural selection shaped our biologic pathways. Validation
      of our hypothesis may shed more light on the biology of cancer and reveal novel
      diagnostic and therapeutic strategies.

PMID- 15236803
TI  - Hypertrophic osteoarthropathy may be a marker of underlying sympathetic bias.
AB  - Hypertrophic osteoarthropathy (HOA) is a condition that accompanies many
      seemingly unrelated diseases. It is commonly associated with various clinical
      conditions such as pregnancy, aging, pulmonary diseases, cancers, and other
      systemic illnesses. The condition has been attributed to various causes such as
      platelet abnormalities, hormonal disturbances, and cytokine dysfunction, but the
      exact underlying mechanism has been elusive. We propose a unifying hypothesis
      that activation of the adrenergic system is the common thread that links all of
      the disparate clinical associations of hypertrophic osteoarthropathy. In diseased
      states, autonomic stimulation may occur as a result of chemoreceptor activation
      in response to acidosis, hypoxia, or hypercapnia. Examples include sleep apnea,
      congestive heart failure, renal failure, and tumor-induced hypoxia. In this
      setting, clinical signs of HOA may be a marker of underlying autonomic
      dysfunction. Autonomic stimulation may also occur as a normal part of pregnancy
      or as an abnormal component of aging. The exact pathway linking adrenergic excess
      to HOA remains to be clarified, but a plausible scenario based on current
      molecular evidence is offered.

PMID- 15236804
TI  - Modulation of host immunity by HIV may be partly achieved through usurping host
      autonomic functions.
AB  - Modulation of host immunity has been observed in human immunodeficiency virus
      (HIV) infections. HIV is believed to influence host immunity through a variety of
      mechanisms including direct effects on host T cell survival, indirect effects on
      cytokine profile through modulation of immune cells, and modulation of endocrine
      functions that affect immunity such as steroids. We hypothesize that HIV
      infection may also alter host immunity through modulation of host sympatho-vagal
      balance. Specifically, we propose that HIV drives autonomic balance towards
      sympathetic bias, which can contribute to a T helper (Th)2 type immunity. A
      variety of paraviral syndromes associated with HIV infection such as QT
      prolongation, cachexia, cardiomyopathy, and lipodystrophy are consistent with
      evidence of autonomic dysfunction. Immunomodulatory effects of autonomic
      dysfunction toward Th2 bias are presented. A plausible mechanism by which HIV can
      influence autonomic balance through hypothalamic manipulation is offered. Shift
      to Th2 dominance is associated with HIV disease progression and can be viewed as
      a viral adaptation to promote its own survival. Autonomic remodeling by HIV may
      exemplify this phenomenon. Our hypothesis has implications for treatment of HIV
      and its associated syndromes.

PMID- 15236805
TI  - Do neural correlates of consciousness cause conscious states?
AB  - Neural correlates of consciousness (NCCs) have been defined as neural systems and
      states of those systems, which are correlated with certain states of
      consciousness and which are minimally sufficient for these states of
      consciousness to occur. Here, it is discussed whether based on the identification
      of a NCC one may claim that this neural correlate causes the corresponding state
      of consciousness. In a strict sense, neural states and corresponding states of
      consciousness should occur simultaneously according to the definition of NCCs.
      However, two causally related events should occur consecutively in time according
      to the general view. Thus, within the NCC framework the question of a causal
      psychoneural relationship is only valid under the premise of a small and
      practically unobservable time shift between neural states and corresponding
      states of consciousness. The term causality is usually applied either in the
      sense of efficient causation or in the sense of explanatory causation. Efficient
      causality addresses the physical relation of two events and the criterion of an
      energy exchange between both events. Explanatory causality, on the other hand,
      refers to the law-like character of the conjoined occurrence of two events. Under
      a dualistic point of view, the interpretation that neural states effectively
      cause consciousness would not be justified, since effective causation, as
      understood in physical sciences, should be associated with energy transfer. But
      such an energy transfer between the domain of consciousness and the neural domain
      would violate presently accepted physical laws. Therefore, it is argued that one
      may state that neural states cause states of consciousness only in the broad
      sense of explanatory causality with regard to the observation of a law-like
      psychoneural relation. Within the viewpoint of identity theory, however, one
      would rather claim that certain states of consciousness basically are neural
      states.

PMID- 15236806
TI  - An experiment on infertility illuminates prostaglandins in natural selection.

PMID- 15236807
TI  - Symptom severity and quality of life after benzodiazepine withdrawal treatment in
      participants with complicated dependence.
AB  - The aims of the present study were to assess changes in psychopathology and
      quality of life after withdrawal treatment in participants with benzodiazepine
      dependence that was in most cases complicated by harmful and hazardous alcohol
      use or high benzodiazepine doses. Seventy-six participants with benzodiazepine
      dependence (DSM-III-R) who participated in a randomized clinical trial of two
      different gradual withdrawal treatment approaches were initially assessed by
      Symptom Checklist-90 (SCL-90), visual analogue scales (VASs), and the Health
      Related Quality of Life battery (HRQOL). The assessments were repeated after
      treatment ended and again after a follow-up averaging 11 months. During the
      study, all measurements for the participants with clinically significant (over
      50%) benzodiazepine-dose decreases improved more than those for the participants
      with smaller decreases, and differences in the HRQOL energy/vitality, home
      management, and life satisfaction scores were significant. Our data indicate that
      in participants with complicated benzodiazepine dependence, clinically
      significant dose decreases are associated with improvements in their self-rated
      quality of life.

PMID- 15236808
TI  - Addressing tobacco among individuals with a mental illness or an addiction.
AB  - Tobacco dependence among individuals with a mental illness or an addiction is a
      tremendous problem that goes largely ignored. Studies of genetics, neuroimaging,
      and nicotinic receptors support a neurobiological link between tobacco use and
      alcohol dependence, drug dependence, schizophrenia, depression, attention-deficit
      hyperactivity disorder (ADHD), and anxiety disorders. This paper summarizes the
      recent literature on this topic and discusses how treatment for tobacco can no
      longer be ignored in mental-health and addiction-treatment settings. More
      research is needed as well as a national organized effort to address tobacco in
      this large segment of smokers.

PMID- 15236809
TI  - Changes in route of drug administration among continuing heroin users: outcomes 1
      year after intake to treatment.
AB  - This study investigates the type and extent of changes in route of drug
      administration among heroin users after treatment: whether injectors move to
      other routes of use; whether changes in route for one drug influence routes used
      for other drugs; and associations between changes in route of administration and
      other substance use outcomes. The sample comprised 641 heroin users recruited to
      54 UK treatment programmes. At intake, the main routes of heroin use were
      injecting (61%) and "chasing the dragon" (37%). After 1 year, 81% of those using
      heroin took it by the same route as at intake, while 19% reported a change, with
      14% switching from injecting to chasing. Changes from injecting to chasing were
      associated with improvements in other substance use behaviours. Changes in route
      represent an important aspect of drug-taking behaviours. Interventions to prevent
      the change to injecting should be developed and offered to noninjectors. "Reverse
      transitions" (from injecting to chasing) may represent a useful intermediate
      treatment goal for drug injectors who cannot achieve abstinence.

PMID- 15236810
TI  - Substance use, religiosity, and other protective factors among Hungarian
      adolescents.
AB  - A number of risk factors have emerged as important correlates of adolescent
      substance use. In addition, research continues to focus on which factors act as
      mediators protecting adolescents from negative outcomes. One of these protective
      factors is religiosity, and the focus of this paper is to examine its role in the
      life of adolescents in postsocialist Hungary, where active religious
      participation was highly discouraged until a decade ago. The sample of
      adolescents (N=1240) consists of middle and high school students living in
      Szeged, Hungary. The calculated odds ratios for the relationship between
      religiosity, and other protective factors, and substance use revealed that
      smoking, drinking, and marijuana use among boys and marijuana use only among
      girls were related to religiosity. Group membership, for example, participation
      in school clubs, sports clubs, or religious groups, seems to be more important
      for boys compared with girls. A more careful examination of the protective role
      of religion in postsocialist Hungary could be extremely important in a country
      where both adult and adolescent smoking and alcohol use is among the highest in
      Europe.

PMID- 15236811
TI  - Cognitive coping skills and depression vulnerability among cigarette smokers.
AB  - Cigarette smokers vulnerable to depression experience considerable difficulty in
      quitting smoking, possibly because they use smoking to manage negative affect and
      possess underdeveloped alternative coping skills for doing so. Efforts to adapt
      cognitive behavior therapy (CBT) of depression to the treatment of depression
      vulnerable smokers have achieved inconsistent results. This research tested one
      possible explanation for these mixed results, the possibility that depression
      vulnerable smokers are not actually deficient in the skills taught in CBT.
      Regular smokers with a history of major depression, but not currently in a
      depressive episode (n = 66), scored worse than did the never-depressed smokers (n
      = 68) on the Ways of Responding [WOR; Behav. Assess. 14 (1992) 93] test of skills
      for coping with negative moods and automatic thoughts. Results were similar in
      analyses using self-rated depression proneness, rather than interview-based
      diagnosis of past major depression, as the marker of depression vulnerability.
      Results were (nonsignificantly) stronger for Caucasian (n = 54) than for African
      American (n = 73) smokers. Implications for future research on cognitive coping,
      CBT, and smoking are discussed.

PMID- 15236813
TI  - College-student smoking: an initial test of an experiential dissonance-enhancing
      intervention.
AB  - This study was designed as an initial test of whether an experiential learning
      intervention, based on cognitive dissonance theory, would increase college
      student smokers' intentions to quit smoking. One hundred forty-four college
      smokers were asked to prepare educational videos about (1) the risks of smoking
      or (2) the feasibility of quitting (in a 2 x 2 factorial design). Main effects
      for the experimental manipulations were not found. However, an interaction
      suggested that intentions to quit smoking were increased by either manipulation,
      but that the effects were not additive. In addition, risk perceptions were
      increased by the health-risk manipulation alone, but not when quitting
      feasibility was also targeted. As predicted, smoking history and smoking-related
      expectancies were both correlated with magnitude of dissonance. Moreover,
      dissonance magnitude was associated with the reported use of dissonance-reducing
      strategies, including intending to quit smoking and believing that tobacco use
      was out of their control due to nicotine addiction. The findings from this
      initial analogue study suggest that attitudes and intentions to quit smoking can
      be influenced by a brief experiential intervention.

PMID- 15236812
TI  - Sex differences in cocaine-dependent individuals' response to disulfiram
      treatment.
AB  - The objective of this study is to evaluate differential response to disulfiram
      treatment of cocaine dependence by sex. Sex by treatment interactions from two
      pooled randomized clinical trials involving 191 cocaine-dependent subjects (36%
      female) were evaluated. Primary outcomes were days of abstinence and percentage
      of drug-free urine specimens. Significant sex by treatment interactions were
      found, where men treated with disulfiram had better outcomes than those who were
      not. Women had an intermediate outcome regardless of whether they received
      disulfiram. Sex differences in response to disulfiram treatment have important
      clinical and theoretical implications. Reasons for this apparent sex-based
      response are not clear, but possible mechanisms worthy of greater study include
      differences in alcohol use by sex as well as differences in dopamine-mediated
      responses to cocaine and disulfiram.

PMID- 15236814
TI  - Achieving abstinence by treating depression in the presence of substance-use
      disorders.
AB  - BACKGROUND: Antidepressants can have an effect on depressive symptoms in
      participants with comorbid drug or alcohol dependence and mood disorder, but
      their effect on drug use is not known. It has been suggested that adding
      psychosocial intervention to antidepressants would enhance the effect on drug
      use. METHOD: A meta-analysis was conducted on trials of antidepressants for this
      comorbidity with and without psychosocial treatment. RESULTS: Studies using
      cognitive-behavioural therapy (CBT) found no medication effect, whereas with no
      intervention, medication was superior to placebo, manualised counselling falling
      in between. CONCLUSION: There is no evidence that antidepressant medication is
      more efficacious in reducing drug use with conjunctive psychosocial treatment.
      Antidepressant medication and psychotherapy may both be useful in the treatment
      of substance-dependent depressed patients, but combining psychotherapy and
      medication may only be useful in patients failing to respond to one treatment.

PMID- 15236815
TI  - Predictors of smoking intentions and smoking status among nonsmoking and smoking
      adolescents.
AB  - PURPOSE: To examine predictors of smoking intentions among current adolescent
      nonsmokers and smokers as well as risk factors associated with smoking status.
      METHODS: Adolescents (N=237), ages 12 through 18 years, were asked to complete a
      questionnaire that assessed smoking behavior and variables thought to be related
      to smoking. Cognitive-motivational variables including perceived vulnerability
      and optimism, not previously examined in adolescent smoking studies, were also
      included. RESULTS: Parental smoking, higher perceived instrumental value, higher
      risk taking/rebelliousness, higher perceived vulnerability, and older age
      increased the odds of an adolescent being a smoker. Greater intentions to smoke
      among nonsmokers was best predicted by peer influences, less knowledge, and
      higher perceived instrumental value. Smokers with lower intentions to quit
      perceived greater instrumental value of smoking. CONCLUSIONS: There are important
      distinctions between the factors that prompt intentions to smoke and to quit
      smoking. Smoking prevention/cessation programs will need to address specific
      factors that distinguish adolescents at varying stages of risk.

PMID- 15236816
TI  - Defining a never-smoker: results from the nonsmokers survey.
AB  - The U.S. Centers for Disease Control defines a never-smoker as someone who has
      smoked < 100 cigarettes per lifetime. In an attempt to explore differences among
      nonsmokers and to validate this cutpoint, we surveyed 69 nonsmokers who had
      smoked between 1 and 200 cigarettes in their lifetime on their experiences during
      the time they smoked. Of the 7 who classified themselves as ex-smokers, 2 met DSM
      IV criteria for nicotine dependence, compared with none who classified themselves
      as never-smokers. No respondents provided data permitting the computation of a
      Fagerstrom Test for Nicotine Dependence (FTND) score. Withdrawal effects were
      minimal, but craving, tolerance, and subjective effects showed a pattern of
      significant differences that were most prominent between those who smoked only 1
      cigarette and those who smoked at least a pack. Our data indicate a graded effect
      but also suggest that 19 cigarettes per lifetime is a more conservative cutpoint
      than 99 for defining the never-smoker phenotype. Further investigation of the
      smoking trajectory and characteristics associated with development of signs of
      dependence in never- vs. ever-smokers may help refine this cutpoint and shed
      light on what protects some people who experiment with smoking from becoming
      chronic users.

PMID- 15236817
TI  - Smoking behavior and interest in quitting among homeless smokers.
AB  - OBJECTIVES: To examine smoking behavior in homeless persons, including the impact
      of self-reported tobacco-related health problems and drug and alcohol abuse on
      readiness to quit and interest in smoking cessation counseling. METHODS: Cross
      sectional survey of outpatients and inpatients on the homeless service at
      Massachusetts General Hospital. RESULTS: Among 98 homeless smokers with a mean
      age of 44 years, tobacco-related medical diagnoses and symptoms and psychiatric
      illnesses were common, as were drug and alcohol abuse. One third of the smokers
      in this sample intended to quit smoking within the next 6 months, including 19%
      who planned to quit in the next 1 month. Forty-four percent of the participants
      were somewhat or very interested in smoking cessation counseling. In multivariate
      analyses, significant (P < .05) predictors of readiness to quit smoking were
      greater confidence in one's ability to quit (self-efficacy) and more social
      support for quitting. Multivariate predictors of interest in smoking cessation
      counseling were smoking-related symptoms and higher self-efficacy for quitting.
      CONCLUSIONS: Homeless smokers recruited from the inpatient and outpatient
      services of a large, urban teaching hospital reported interest in both stopping
      tobacco use and receiving assistance to quit smoking. Having an illness that a
      smoker believes is tobacco-related, having greater confidence in the ability to
      quit, and having more social support for quitting were associated with greater
      readiness to quit and more interest in smoking cessation counseling. Alcohol and
      drug abuse were not associated with reduced interest in quitting smoking. These
      findings suggest that homeless smokers may benefit from smoking cessation
      programs that are colocated in medical or drug treatment settings.

PMID- 15236818
TI  - Measuring accuracy of self-reported vehicular offences and blood alcohol
      concentration levels among whites and Mexican Americans mandated to drinking
      driver programs.
AB  - BACKGROUND: Differences in self-reported rates of drinking and driving compared
      to official statistics have been found for Hispanics compared to whites, and is
      thought to be related to underreporting among Hispanics. METHODS: Self-reported
      and California Department of Motor Vehicles (DMV)-reported number of vehicular
      offences and blood alcohol concentration (BAC) levels were compared between a
      sample of 249 respondents of Mexican descent (half of whom were born in Mexico)
      and 250 white non-Hispanics convicted of driving under the influence of alcohol
      (DUI) in all five DUI treatment programs in one Northern California county.
      RESULTS: Of those Mexico-born respondents, 11% underreported compared to 7% for
      their America-born counterparts, while 3% of whites underreported. In addition,
      Mexico-born respondents underreported BAC levels more, on average, when comparing
      to DMV reports than their America-born counterparts and whites. Underreporting of
      BAC level was positively associated with individuals' negative attitudes towards
      drinking and negatively associated with frequency of heavy drinking, alcohol
      dependence, and the number of safety-related tickets or DUIs in the past year.
      CONCLUSIONS: Interview data combined with DMV data suggest that there are ethnic
      differences in accuracy of reporting vehicular offences and BAC levels,
      consistent with those found from other studies.

PMID- 15236819
TI  - Relationship between education and delay discounting in smokers.
AB  - Smokers are less educated and are more likely to discount future rewards than
      nonsmokers. We assessed the relationship between delay discounting and education
      level in 77 smokers entering smoking cessation treatment. There was an effect of
      education on computer task and the questionnaire measures of discounting, with
      participants having no college discounting delayed rewards significantly (P <
      .01) more than those attending college. Subjects discounted small rewards more
      than large rewards for both tasks (P < .001). Results show that education level
      is inversely associated with discounting in smokers.

PMID- 15236820
TI  - Adverse childhood events, substance abuse, and measures of affiliation.
AB  - Adverse childhood events may influence later behaviors, including adulthood
      substance use and social affiliation. Studies have noted high prevalence rates of
      adverse childhood experiences and adulthood substance abuse among homeless
      adults. Using an existing longitudinal, countywide probability sample of 397
      homeless adults, we examine the relationships among adverse childhood events on
      adulthood substance use, and the relationship of these variables to affiliation.
      Almost 75% of the sample had experienced an adverse childhood event. Path
      analysis indicated adulthood substance abuse mediated the inverse relationship
      between adverse childhood events and two measures of adulthood affiliation. Thus,
      although there is a relationship between adverse childhood events and adulthood
      substance use, it is adulthood substance use that determines most aspects of
      affiliation.

PMID- 15236821
TI  - Enlarged double-blind randomised trial of benzodiazepines against psychotropic
      analgesic nitrous oxide for alcohol withdrawal.
AB  - We report a randomised double-blind controlled study with an enlarged cohort of
      participants (N = 51) using psychotropic analgesic nitrous oxide (PAN) versus
      benzodiazepines (BZs) for treating acute alcoholic withdrawal states. An
      additional 28 participants having received a BZ the night previous to the study
      were pooled with the previously analysed 23 (with no additional BZ). These pooled
      results showed that PAN is superior to a BZ regimen at P = .05 level, despite
      additional BZs. Our work provides further support for previous findings that show
      that PAN is a safe, rapid, and effective therapy for acute mild to moderately
      severe withdrawal states.

PMID- 15236822
TI  - Drug injection cessation among HIV-infected injecting drug users.
AB  - This article reports findings from a cohort study that investigated drug
      injection cessation over an 18-month period among HIV-infected injecting drug
      users followed up in a clinical setting. At 18th month visit, individuals
      reporting persistent injection practices were compared with individuals who
      reported drug injection cessation for at least 12 months. Crude and adjusted odds
      ratios were used to assess the impact of change in addictive and sexual
      behaviors, contacts with the drug network, depression, negative life events,
      clinical status, HIV therapy, and drug maintenance treatment (DMT) on drug
      injection cessation. After multiple adjustment, a general decrease of addiction
      practices (alcohol and cannabis) and of unsafe sexual behaviors significantly
      accompanied injection cessation. Individuals with higher education level, still
      in contact with the drug network, and not yet treated for their HIV disease were
      significantly more likely to persist injecting behaviors. These results
      underscore the importance and the need of monitoring addiction practices and
      unsafe sexual behaviors among HIV-positive individuals to properly address
      primary and secondary prevention in the era of highly active antiretroviral
      treatments (HAART).

PMID- 15236823
TI  - Excessive drinking in college: behavioral outcome, not binge, as a basis for
      prevention.
AB  - The dichotomous variable "binge drinking" and its associated outcomes may be
      insufficient for understanding the drinking phenomenon on college campuses. The
      current study examined the behavioral outcomes associated with different drinking
      nights (light, typical, and heavy) in an effort to more closely examine
      collegiate drinking behavior. Data were collected from 236 university students,
      including hourly drinking rate, estimated blood alcohol concentration (BAC) was
      computed, and outcomes for each drinking night. Students reported drinking
      behavior that ranged from weekly "light night" drinking (average: 2.85 drinks,
      3.34 h, end of night BAC = 0.04%) to biweekly "heavy nights" (average: 9.91
      drinks, 4.93 h, end of night BAC = 0.25%). Students report encountering the
      greatest number of negative outcomes during heavy drinking nights, while light
      nights were found to have the fewest associated negative outcomes. Positive
      outcomes were highest on "typical" nights, although effect sizes were small.
      These data suggest that prevention efforts may be more successful if types of
      drinking night and positive outcomes become a stronger focus. Limitations and
      directions for future programming and research are discussed.

PMID- 15236824
TI  - A short form of the Fagerstrom Test for Nicotine Dependence and the Heaviness of
      Smoking Index in two adult population samples.
AB  - Few data exist about the Fagerstrom Test for Nicotine Dependence (FTND) and the
      Heaviness of Smoking Index (HSI) from population samples. The goal was to prove
      to what degree (1) a reduced item solution of the FTND and (2) the HSI represent
      the FTND. Two randomized adult population samples were used from northern
      Germany. Sample 1 included 1462 and sample 2 included 1042 current daily
      cigarette smokers aged 20-64 years with FTND data. The results show that four
      items of the FTND as well as the HSI represent the FTND. It is concluded that
      both are valid measures of the urge to smoke and the tobacco-smoke-seeking
      behavior.

PMID- 15236825
TI  - The effects of cannabis on information-processing speed.
AB  - Despite extensive research on the effects of cannabis on cognitive and motor
      performance, studies administering computerised cognitive batteries and pencil
      and-paper tests have not provided consistent results. Contributing factors are
      the broad range of tests used, together with a lack of sensitivity for assessing
      specific cognitive processes. This study for the first time assesses a very early
      cognitive process, information processing, that is sufficiently fundamental as to
      be immune from higher cognitive, motivational, and social processes. Information
      processes are thought to represent the basic building blocks of higher order
      cognitive processes. The inspection time (IT) task was used to investigate the
      effects of acute and subacute cannabis use on information processing in 22 heavy
      users, compared to 22 noncannabis-using controls. Findings indicate that users in
      the subacute state display significantly slowed information-processing speeds
      (longer ITs) compared to controls. Paradoxically, this deficit appears to be
      normalised whilst users are in the acute state. These results may be explained as
      a withdrawal effect, but may also be due to tolerance development as a result of
      long-term cannabis use. Furthermore, these results may assist in providing an
      explanation for the development of dependence with chronic cannabis users.

PMID- 15236826
TI  - The moderating effects of tension-reduction alcohol outcome expectancies on
      placebo responding in individuals with social phobia.
AB  - We conjectured that individual differences in tension-reduction alcohol outcome
      expectancies (TR-AOEs) could produce widely varying responses to manipulations in
      alcohol-placebo studies and tested this idea by having individuals with social
      phobia give speeches in front of a group. One speech occurred before and one
      after participants consumed either a placebo beverage or a control beverage
      (i.e., a nonalcoholic drink described as containing no alcohol). Study results
      indicate that the placebo manipulation reduced cognitive and affective symptoms
      of anxiety to a greater extent for males with high TR-AOEs than for males with
      low TR-AOEs. This pattern was not found for women in the placebo group or for
      individuals in the control group. These findings demonstrate a moderating effect
      of TR-AOEs on the association between the consumption of a placebo beverage and
      response to an anxiety challenge and highlight the importance of accounting for
      gender and outcome expectancies when evaluating psychoactive substances.

PMID- 15236827
TI  - Nonpharmacological harm-reduction interventions in British substance-misuse
      services.
AB  - The present study was designed to assess the acceptability and availability of
      harm-reduction interventions, including needle exchange, education regarding
      safer drug-ingestion methods, complementary/alternative therapies, and safe
      places where problem drinkers and drug takers may stay after consumption or may
      consume substances on the premises. We surveyed a nationwide sample of agencies
      listed in directories of substance-abuse services in England, Wales, and
      Scotland. Seventy percent (436 of 623 eligible agencies) returned questionnaires.
      Except for the provision of a safe place where clients could consume their own
      alcohol and drugs, large majorities of responding agencies rated these harm
      reduction options as somewhat or completely acceptable, but only harm-reduction
      education and alternative therapies were available from a majority of responding
      agencies.

PMID- 15236828
TI  - Pathological gambling, gender, and risk-taking behaviors.
AB  - Seventy-eight female and 78 male pathological gamblers admitted to an outpatient
      treatment program were compared regarding a profile of risk-taking behaviors
      (suicide attempts, illegal activities meant to finance gambling, sexual risky
      behavior, and alcohol abuse). The Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN), the Barratt Impulsiveness Scale version 11 (BIS-11), and
      an adaptation of the HIV Risk Behavior Scale were used. Females attempted more
      suicide than males. Men had more sexual risky behavior and alcohol abuse than
      women. Younger age and depression were risk factors for suicide attempts, younger
      age and impulsivity were risk factors for illegal activities. Younger age was a
      risk factor for sexual risky behavior, and no risk factor other than male gender
      was found for alcohol abuse. Future investigation of risk behaviors among
      gamblers must take into account the differences in gender and age. Both
      impulsivity and emotional distress are related to risk-taking in gamblers, and
      young gamblers who early in life display other potentially harmful behaviors
      require special attention.

PMID- 15236829
TI  - Five-year prospective prediction of marijuana use cessation of youth at
      continuation high schools.
AB  - This paper reports the prediction of marijuana use cessation among young adults
      who were regular users 5 years earlier. Social, attitude, intrapersonal, violence
      related, drug use, and demographic baseline measures served as predictors of
      whether or not 339 teenage marijuana users reported having quit use 5 years
      later. Young adult social role variables were included as additional predictors.
      Quitting was defined as having not used marijuana in the last 30 days (42% of the
      sample at follow-up). After controlling for covariation among predictors, in a
      three-step analysis, only baseline level of marijuana use, male gender, young
      adult marital status, and friends' marijuana use (marginal) remained
      statistically direct predictors. Implications of these results include the need
      to reduce psychological dependence on marijuana and increase social
      unacceptability of marijuana use across genders to help increase prevalence of
      quit attempts.

PMID- 15236830
TI  - Relationship between early experiences with tobacco and early experiences with
      alcohol.
AB  - Initial sensitivity to substances may affect patterns of future use and
      dependence. Because smoking and alcohol use are strongly linked, because animal
      studies indicate cross-sensitivity, and because genetic determinants of nicotine
      and alcohol dependence overlap, we studied the relationships between
      retrospectively reported responses to both substances in current smokers (n =
      111) and never-smokers (n = 86). Early smoking experiences were correlated with
      comparable responses to alcohol in smokers, and to a lesser extent, in never
      smokers. Both pleasurable early experiences with nicotine and pleasurable
      experiences with alcohol predicted current alcohol intake; pleasurable early
      experiences with alcohol also predicted alcohol dependence. Neither pleasurable
      nor displeasurable experiences with either substance predicted current amount
      smoked or degree of nicotine dependence. These preliminary findings may have
      implications for understanding the mechanisms underlying the smoking-alcohol
      link.

PMID- 15236831
TI  - Naltrexone and brief counseling to reduce heavy drinking in hazardous drinkers.
AB  - The present study examined the utility of daily naltrexone for decreasing alcohol
      drinking in hazardous drinkers. Forty-one participants participated in a 10-week
      trial and received 30 min of brief counseling on the first and second week of
      treatment, as well as a daily dose of 50 mg of naltrexone throughout the trial.
      Overall, naltrexone-treated participants did not show the same degree of
      improvement on drinking outcomes as placebo-treated participants. The placebo
      group drank fewer drinks per drinking day and achieved more abstinence days than
      the naltrexone group. Craving was also lower for the placebo group. The groups
      were not balanced on gender or family history of alcoholism and this may explain
      the lack of effect of naltrexone on the drinking outcomes.

PMID- 15236832
TI  - Gender, smoking expectancies, and readiness to quit among urban African American
      smokers.
AB  - The relationship between smoking expectancies and readiness to quit as well as
      gender differences in expectancies and readiness to quit was examined among 484
      urban African American smokers. Univariate analyses revealed that higher positive
      expectancies were generally associated with less readiness to quit and higher
      negative expectancies were associated with greater readiness to quit. A
      multivariable model indicated that stimulation/state enhancement,
      taste/sensorimotor manipulation, and weight control were most strongly related to
      intention to quit. Although men and women did not differ on readiness to quit,
      women reported higher scores on the negative affect reduction subscale than did
      men.

PMID- 15236833
TI  - Smoking stage of change is associated with retention in a smoke-free residential
      drug treatment program for women.
AB  - Prochaska and DiClemente's Transtheoretical Model predicts dropout from substance
      abuse treatment. However, it is not known whether readiness to quit smoking is
      associated with attrition from drug treatment programs with smoking restrictions.
      This study examined the relationship between smoking characteristics, smoking
      stage of change, and both length of stay (LOS) and discharge type among 75
      perinatal substance abusers attending a smoke-free residential treatment program.
      URICA scores predicted LOS (P=.0004) and discharge type (P=.01). Women in action
      and maintenance remained in treatment longer and were more likely to complete
      treatment compared to those in precontemplation. Findings were not accounted for
      by addiction severity. Women with little interest in quitting smoking may have
      difficulty adhering to smoking restrictions during treatment for other drug
      problems, resulting in increased attrition. Alternatively, smoking stage of
      change may be a "proxy" for overall readiness to change in this population.

PMID- 15236834
TI  - Genes, proteins, and neurotoxins involved in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder. The etiology of
      PD is likely due to combinations of environmental and genetic factors. In
      addition to the loss of neurons, including dopaminergic neurons in the substantia
      nigra pars compacta, a further morphologic hallmark of PD is the presence of Lewy
      bodies and Lewy neurites. The formation of these proteinaceous inclusions
      involves interaction of several proteins, including alpha-synuclein, synphilin-1,
      parkin and UCH-L1. Animal models allow to get insight into the mechanisms of
      several symptoms of PD, allow investigating new therapeutic strategies and, in
      addition, provide an indispensable tool for basic research. In animals PD does
      not arise spontaneously, thus, characteristic and specific functional changes
      have to be mimicked by application of neurotoxic agents or by genetic
      manipulations. In this review we will focus on genes and gene loci involved in
      PD, the functions of proteins involved in the formation of cytoplasmatic
      inclusions, their interactions, and their possible role in PD. In addition, we
      will review the current animal models of PD.

PMID- 15236835
TI  - Has dopamine a physiological role in the control of sexual behavior? A critical
      review of the evidence.
AB  - The role of dopaminergic systems in the control of sexual behavior has been a
      subject of study for at least 40 years. Not surprisingly, reviews of the area
      have been published at variable intervals. However, the earlier reviews have been
      summaries of published research rather than a critical analysis of it. They have
      focused upon the conclusions presented in the original research papers rather
      than on evaluating the reliability and functional significance of the data
      reported to support these conclusions. During the last few years, important new
      knowledge concerning dopaminergic systems and their behavioral functions as well
      as the possible role of these systems in sexual behavior has been obtained. For
      the first time, it is now possible to integrate the data obtained in studies of
      sexual behavior into the wider context of general dopaminergic functions. To make
      this possible, we first present an analysis of the nature and organization of
      sexual behavior followed by a summary of current knowledge about the brain
      structures of crucial importance for this behavior. We then proceed with a
      description of the dopaminergic systems within or projecting to these structures.
      Whenever possible, we also try to include data on the electrophysiological
      actions of dopamine. Thereafter, we proceed with analyses of pharmacological data
      and release studies, both in males and in females. Consistently throughout this
      discussion, we make an effort to distinguish pharmacological effects on sexual
      behavior from a possible physiological role of dopamine. By pharmacological
      effects, we mean here drug-induced alterations in behavior that are not the
      result of the normal actions of synaptically released dopamine in the untreated
      animal. The conclusion of this endeavor is that pharmacological effects of
      dopaminergic drugs are variable in both males and females, independently of
      whether the drugs are administered systemically or intracerebrally. We conclude
      that the pharmacological data basically reinforce the notion that dopamine is
      important for motor functions and general arousal. These actions could, in fact,
      explain most of the effects seen on sexual behavior. Studies of dopamine release,
      in both males and females, have focused on the nucleus accumbens, a structure
      with at most a marginal importance for sexual behavior. Since accumbens dopamine
      release is associated with all kinds of events, aversive as well as appetitive,
      it can have no specific effect on sexual behavior but promotes arousal and
      activation of non-specific motor patterns. Preoptic and paraventricular nucleus
      release of dopamine may have some relationship to mechanisms of ejaculation or to
      the neuroendocrine consequences of sexual activity or they can be related to
      other autonomic processes associated with copulation. There is no compelling
      indication in existing experimental data that dopamine is of any particular
      importance for sexual motivation. There is experimental evidence showing that it
      is of no importance for sexual reward.

PMID- 15236836
TI  - Orally active PDE4 inhibitor with therapeutic potential.
AB  - Based on the promising results obtained by the clinical trial of Ariflo, further
      optimization of the spatial arrangement of the three pharmacophores (the
      carboxylic acid moiety, nitrile moiety and 3-cyclopentyloxy-4-methoxyphenyl
      moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3 ?3 ?0]octane
      template with more stereochemical diversity than the cyclohexane template of
      Ariflo 1. Biological evaluation of the decyanated analogs and further
      optimization of the cyclopentyloxy moiety of 2a-b were also performed. Among the
      compounds tested, 2a, 7a-b and 12a were found to be orally active and were
      estimated to have therapeutic potential based on cross-species and same-species
      comparisons. The structure-activity relationships (SARs) of these compounds were
      investigated and pharmacokinetic data for 2a and 7b were also obtained by single
      dose studies in rats.

PMID- 15236837
TI  - Fluoro-substituted and 13C-labeled styrylbenzene derivatives for detecting brain
      amyloid plaques.
AB  - Two styrylbenzene derivatives, (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4
      hydroxy)styrylbenzene (FSB) and (E,E)-1-bromo-2,5-bis(3-hydroxycarbonyl-4
      hydroxy)styrylbenzene-alpha,alpha'-(13)C(2) ([(13)C]BSB), were synthesized for
      use as a histochemical stain to detect amyloid plaques of Alzheimer's disease
      (AD) brain sections. An analysis of fluorescence spectra demonstrated that FSB
      shows approximately twofold fluorescence intensity relative to the conventional
      styrylbenzene derivative, (E,E)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4
      hydroxy)styrylbenzene (BSB). Moreover, FSB was found to stain amyloid plaques and
      neurofibrillary tangles of AD brains with greater fluorescence intensity and a
      lower level of background signals compared to BSB. These finding indicate that
      FSB can be an excellent fluorescent compound to label human amyloid lesions with
      high sensitivity and specificity. Because of the possession of a nuclide with a
      quantized angular momentum, both FSB and [(13)C]BSB are also potential contrast
      agents for magnetic resonance imaging to locate AD pathologies in vivo.

PMID- 15236838
TI  - Synthesis of novel substituted tetrazoles having antifungal activity.
AB  - In an effort to find potent antifungal agents, a variety of triazole derivatives
      with a 5-substituted tetrazole structure 6, 7, 12 and 14 were prepared and
      evaluated for antifungal activity against Candida spp., Cryptococcus neoformans,
      and Aspergillus spp. in vitro. The location of the methyl group at the C-3 of
      compounds 12 and 14 has been demonstrated to be a key structural element of
      antifungal potency.

PMID- 15236839
TI  - QSAR study on carbonic anhydrase inhibitors: aromatic/heterocyclic sulfonamides
      containing 8-quinoline-sulfonyl moieties, with topical activity as antiglaucoma
      agents.
AB  - Quantitative structure-activity-relationship (QSAR) study on
      aromatic/heterocyclic sulfonamides containing 8-quinoline-sulfonyl carbonic
      anhydrase (CA) inhibitors has been carried out topologically using first-order
      valence connectivity index ((1)chi(v)). Excellent results are obtained against
      all the three isozymes; CA I, II and IV of the zinc enzyme CA by using indicator
      parameters along with (1)chi(v).

PMID- 15236840
TI  - Is it possible docking and scoring new ligands with few experimental data?
      Preliminary results on estrogen receptor as a case study.
AB  - Estrogens are steroid hormones playing critical roles in several physiological
      processes, which bind the estrogen receptors ERalpha and ERbeta. Aim of this work
      is to analyze, by different docking experiments, the behavior of a set of
      compounds, mimicking estrogens activity, in order to understand the relationship
      between ERalpha and such new ligands. Main goal is to verify, using a widely
      tested scoring software procedure applied on a set of 10 compounds, the
      possibility to produce new lead candidate molecules in lack of, or with few
      experimental data. Our preliminary results reveal the significance of HINT
      software as a scoring function in docking methodology and specifically, as a mean
      for assessing the consistency of docking solutions.

PMID- 15236841
TI  - Inhibitory effects of L-arginine derivatives on endothelium-dependent
      vasorelaxing response to acetylcholine of the rat aorta.
AB  - N(omega)-nitro-L-arginine alkyl esters (A-1-A-B) and L-arginine alkyl esters (E-1
      E-B) were synthesized, and the vasorelaxing effects of acetylcholine were studied
      in the absence or presence of these compounds in rat aortic rings with intact
      endothelium that was precontracted with phenylephrine. These compounds revealed
      that the nitro group is an essential inhibiting group of these inhibitors, and
      that hydrophobic functional groups can fine-tune the binding effects. Among them,
      A-3 is the most potent inhibitor.

PMID- 15236842
TI  - Cytotoxicity of enantiomers of gossypol Schiff's bases and optical stability of
      gossypolone.
AB  - Optical Schiff's bases of gossypol were prepared with chiral gossypol and
      ethylamine. As has been similarly observed among the gossypol enantiomers, the (
      )-gossypol ethylimine was more active than either the (+)-gossypol ethylimine or
      the racemic gossypol ethylimine against KB and MCF7 cells. Gossypolone was also
      observed to be more toxic than gossypol against both cell lines. All of the
      gossypol products tested showed comparable toxicity toward MCF7/ADR (adriblastine
      resistant) cells. Attempts at producing chiral gossypolone from chiral gossypol
      failed because of rapid racemization. In addition, the Schiff's base derivatives
      of gossypolone formed with R-(+)-2-amino-3-phenyl-1-propanol could only be
      separated at reduced temperature, indicating that gossypolone Schiff's bases are
      less optical stable than gossypol Schiff's bases.

PMID- 15236843
TI  - Site-directed mutagenesis of the rat beta1-adrenoceptor. Involvement of Tyr356
      (7.43) in (+/-)cyanopindolol but not (+/-)[125Iodo]cyanopindolol binding.
AB  - To determine the role played by Tyr(356 (7.43)) in the rat beta(1)-adrenoceptor
      in binding the antagonists (+/-)cyanopindolol (4-[3-(t-butylamino]-3-(2'-cyano
      indoloxy)-2-propanolol) and its iodinated analogue (+/-)[(125)Iodo]cyanopindolol
      (1-(t-butylamino]-3-(2'-cyano-3'-iodo-indoloxy)-2-propanolol), Tyr(356 (7.43))
      was mutated to either Phe or Ala and binding affinities determined for wild type
      and mutant rat beta(1)-adrenoceptors. Our results indicate that Tyr(356 (7.43))
      is important for (+/-)cyanopindolol, but not (+/-)[(125)Iodo]cyanopindolol,
      binding and that (+/-)cyanopindolol adopts a "reverse" binding orientation
      whereas (+/-)[(125)Iodo]cyanopindolol cannot be accommodated in this binding
      mode. We define a "reverse" antagonist binding mode as one where the aryloxy
      moiety interacts with residues on transmembrane helices 1, 2, 3 and 7. The
      beta(1)-adrenoceptor site-directed mutagenesis results are the first to support a
      "reverse" antagonist binding orientation and the involvement of Tyr(356 (7.43))
      in this binding mode.

PMID- 15236844
TI  - Syntheses and GABA uptake properties of 6-ether- and 6-enol ether-substituted
      nipecotic acids.
AB  - 6-aralkylether- and 6-arylenol-ether-substituted nipecotic acids were
      synthesized. These analogues are poor GABA uptake inhibitors. The electronegative
      region concept developed in the N-substituted nipecotic acid series cannot be
      transferred on the side chain of this series of 6-substituted analogues.

PMID- 15236845
TI  - Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3]naphtho[1,2
      d]imidazoles from beta-lapachone.
AB  - We synthesized new naphthoimidazoles from beta-lapachone with an aromatic moiety
      linked to the imidazole ring, using phenylic and heterocyclic aldehydes. The most
      active compound against Trypanosoma cruzi had a p-methyl group linked to the
      phenyl ring, presenting an EC(50) value of 15.5 +/- 2.9 microM. No reliable
      correlation could be established with the biological activity and the structure
      of in the phenylic series. For the heterocyclic series, activity was associated
      with a three bond-distance from nitrogen to the imidazole ring, in accordance
      with our previous work.

PMID- 15236846
TI  - A comparison of competing methods for the detection of surgical-site infections
      in patients undergoing total arthroplasty of the knee, partial and total
      arthroplasty of hip and femoral or similar vascular bypass.
AB  - Recent research suggests that the retrospective review of the International
      Classification of Disease (ICD-9-CM) codes assigned to a patient episode will
      identify a similar number of healthcare-acquired surgical-site infections as
      compared with prospective surveillance by infection control practitioners (ICP).
      We tested this finding by replicating the methods for 380 surgical procedures.
      The sensitivity and specificity of the ICP undertaking prospective surveillance
      was 80% and 100%, and the sensitivity and specificity of the review of ICD-10-AM
      codes was 60% and 98.9%. Based on these results we do not support retrospective
      review of ICD-10-AM codes in preference prospective surveillance for SSI.

PMID- 15236847
TI  - RSV outbreak in a paediatric intensive care unit.
AB  - The Royal Liverpool Children's Hospital-Alder Hey paediatric intensive care unit
      (PICU) usually has a low rate of nosocomial respiratory syncytial virus (RSV)
      infection. We report and analyse a major outbreak of nosocomial (acquired) RSV
      infection on the PICU during a RSV season. All children admitted to the PICU were
      studied during the six-month winter period 1 October 2002 to 31 March 2002.
      Nasopharyngeal aspirates were tested using an in vitro enzyme-linked immunoassay
      (ELISA) membrane test for RSV antigen. PICU-acquired RSV infection was considered
      to have occurred when a child admitted to the PICU was RSV negative, or from whom
      no samples were taken as they did not exhibit signs of bronchiolitis, but was RSV
      positive five or more days after the admission. Fifty-four patients tested RSV
      positive using the ELISA on the PICU. All the patients were ventilated. Thirty
      nine children were RSV positive using the ELISA on admission to the PICU
      ('imported' cases) and 15 became RSV positive whilst on the PICU ('acquired'
      cases). The source of the acquired RSV infection accounting for the first
      peak/outbreak in nosocomial cases were RSV-positive children in isolation
      cubicles. Acquired cases of RSV infection subsided with reinforcement of
      traditional methods of barrier precautions. The source of the second peak in
      nosocomial cases were persistent shedders of RSV. Seventy-three percent (11/15)
      of the acquired RSV cases had one or more of the following co-morbidities:
      congenital heart disease, chronic lung disease, airways abnormalities or
      immunosuppression. Droplet precautions (strict handwashing, use of gloves if
      handling body fluids, single-use aprons, education) rather than the physical
      barrier of the cubicle itself played a more important role in curtailing
      nosocomial spread. Persistent shedders of RSV are an important potential source
      of nosocomial RSV infection within a PICU. Patients with co-morbidities are at
      increased risk of nosocomial RSV infection.

PMID- 15236848
TI  - Molecular biology of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae responsible for digestive tract colonization.
AB  - Twenty-nine extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      strains (14 Klebsiella pneumoniae, 10 Escherichia coli and five Citrobacter
      diversus) isolated from April to July 1996 from faecal carriers in a surgical
      intensive care unit at the university hospital of Casablanca (Morocco) were
      studied. Plasmid content and DNA macrorestriction polymorphism determined by
      pulsed-field gel electrophoresis (PFGE) were used to compare the strains.
      Restriction profiles of total genomic DNAs cleaved by XbaI and compared by PFGE
      revealed nine, four and two clones in K. pneumoniae, E. coli and C. diversus,
      respectively. Plasmid profile analysis of ESBL-producing strains of K. pneumoniae
      showed that only seven of 14 isolates had a plasmid; four different plasmid
      profiles were observed. Three different plasmid profiles were observed in E. coli
      and two in C. diversus. Plasmids responsible for ESBL production could be
      transferred by conjugation to E. coli K(12) J53-2 from all E. coli isolates and
      from four of seven K. pneumoniae. No plasmid transfer could be obtained from C.
      diversus strains. Restriction enzyme digests of plasmids from transconjugants
      (four transconjugants of K. pneumoniae and five transconjugants of E. coli)
      showed different patterns. In the surgical intensive care unit where the survey
      was conducted, the dissemination of ESBLs was due to a mix of strain spread and
      strain diversity rather than to plasmid dissemination.

PMID- 15236849
TI  - Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection.
AB  - A case-control study was conducted in a university hospital to determine the risk
      factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa
      (MDR-PA) among all hospitalized patients and among those with a nosocomial
      infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected
      with a non-MDR phenotype and 240 random controls were included in the 12-month
      study. Among all hospitalized patients, age, severity index, having a bedridden
      condition, transfer from other units, nasogastric feeding, urinary
      catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones
      (OR=4.1) in the seven days before infection were linked to nosocomial infection
      due to MDR-PA. Among patients infected by P. aeruginosa, exposure to
      fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR
      PA. This study showed that, in addition to urinary catheterization, nasogastric
      feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in
      gut flora, modifications to the mucous membranes due to the use of nasogastric
      feeding and the selection pressures exerted by antibiotics were implicated in the
      occurrence of this infection.

PMID- 15236850
TI  - The influence of laboratory adaptation on test strains, such as Pseudomonas
      aeruginosa, in the evaluation of the antimicrobial efficacy of ortho
      phthalaldehyde.
AB  - The microbiocidal efficacy of 0.55% ortho-pthalaldehyde (OPA) was evaluated in a
      rough carrier test, using more than 200 strains of bacteria and yeasts from
      patients and reference ATCC strains. This test was then compared with the
      European carrier test (prEN14561) using Pseudomonas aeruginosa. We also sought to
      determine whether recently isolated P. aeruginosa had the same susceptibility to
      OPA, after laboratory adaptation. It was shown that P. aeruginosa was less
      susceptible to OPA (being reduced by a factor of 10(3.8)) than the other strains
      (reduced by a factor of 10(4)). The surface test used, produced a lesser
      reduction of P. aeruginosa than the European test. For recently isolated strains
      (N = 66), the rough model demonstrated that the number of survivors increased
      both quantitatively and qualitatively from day one to day seven. It was concluded
      that disinfectant efficacy should be confirmed with recently isolated organisms.

PMID- 15236851
TI  - Reducing ventilator-associated pneumonia rates through a staff education
      programme.
AB  - Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in
      patients on mechanical ventilation and results in increases in mortality,
      prolonged hospitalization and costs. Preventive measures for VAP are well
      documented and evidence-based, yet remain poorly implemented in most intensive
      care units. We undertook an observational pre and post-intervention study to
      assess whether an educational programme focusing on preventive practices for VAP
      could reduce the incidence. Six hundred and seventy-seven adult patients,
      mechanically ventilated for >48 h were included in the study population. An
      evidence-based guideline for preventive practices at the bedside was developed
      and disseminated to the intensive care unit staff. VAP incidence rates before and
      after implementation of the educational programme were compared. VAP infection
      rates reduced by 51%, from a mean of 13.2+/-1.2 in the pre-intervention period to
      6.5+/-1.5/1000 device days in the post-intervention period (mean difference 6.7;
      95% CI: 2.9-10.4, P =0.02). A multidisciplinary educational programme geared
      towards intensive care unit staff can successfully reduce the incidence rates of
      VAP. Further studies will be needed to assess the impact on broader outcome
      measures such as costs or mortality.

PMID- 15236852
TI  - Containment testing of isolation rooms.
AB  - Results from the tracer containment testing of four 'state-of-the-art' airborne
      infection isolation rooms, in a new hospital, are presented. A testing technician
      exited an isolation room several minutes after a small quantity of tracer gas was
      injected over the patient bed in that room. Easily measurable tracer gas
      concentrations were then found in the anterooms outside the patient rooms and
      corridor outside the isolation room suites. Containment factors for the isolation
      rooms and dilution factors in the anterooms and corridor were calculated, based
      on the measured tracer concentrations. These results indicate the desirability of
      evidence-based design standards and guidelines for assessing performance of
      airborne infection isolation rooms. The study also demonstrates that the tracer
      testing procedure yields comparable results for equivalent isolation room suites,
      suggesting good reproducibility of the testing method.

PMID- 15236853
TI  - The microbial content of non-sterile pharmaceuticals distributed in Norway.
AB  - Seventy-seven registered trademark pharmaceuticals and allied products, not
      required by the relevant monographs to comply with the test for sterility, were
      investigated for their microbial content. All the products examined complied with
      current regulations with respect to the numbers and types of microbes isolated,
      indicating the effectiveness of existing production practices in meeting existing
      standards. Gram-positive endospore-forming rods accounted for the majority of the
      bacteria isolated. Gram-negative rods were present for the most part in
      incidental numbers. However, some of these were of species that have been
      previously indicated as opportunistic pathogens and which should be considered as
      objectionable in pharmaceuticals. A number of the isolates showed antibiotic
      resistances unusual for the species in question.

PMID- 15236854
TI  - Incidence of bacteraemia after urodynamic study.
AB  - The aim of the present study was to determine the incidence of bacteraemia after
      urodynamic study (UDS) in patients with lower urinary tract symptoms, and to
      evaluate the role of bacteraemia as a morbidity factor related to UDS. A total of
      57 patients (mean age: 52.8 years, range: 8-76 years) were evaluated by UDS.
      Prophylactic antibiotics were not administered to any of the patients before the
      procedure. Before UDS, urine cultures were examined for the presence of infection
      of the urinary tract (UTI). Venous blood was taken before and just after
      performing UDS. There was no bacterial growth in blood cultures of any patients
      before the UDS. Of the 57 patients, two had bacteriuria before study. After UDS,
      bacteraemia was determined in four (7%) out of 55 patients. The two patients with
      a bacteriuria before the procedure also had positive blood cultures. Infectious
      complications are the most important morbidity factors related to the UDS.
      Despite the use of strict aseptic techniques, bacteraemia may occur in patients
      undergoing UDS. The results of the present study may help when counselling
      patients who are to undergo UDS.

PMID- 15236855
TI  - Risk factors for acquisition of methicillin-resistant Staphylococcus aureus
      (MRSA) by trauma patients in the intensive care unit.
AB  - In a previous study in the intensive care unit (ICU) of the Alfred Hospital,
      Melbourne, Australia, it was demonstrated that trauma patients were at particular
      risk of becoming colonized by methicillin-resistant Staphylococcus aureus (MRSA).
      We examined risk factors for MRSA acquisition in these patients using a cohort
      study comparing the 31 patients who acquired MRSA with 65 who did not. Data
      collected included ICU length of stay (LOS), mechanism of trauma, site of injury,
      type of surgery, trauma severity and antibiotic usage. Odds ratios (OR) were
      determined and adjusted for LOS. LOS in the ICU was a significant univariate
      predictor of MRSA acquisition (OR 13.7). When adjusted for LOS, mechanism of
      trauma (OR 10.4), laparotomy (OR 6.3) and administration of
      ticarcillin/clavulanic acid (OR 4.5) or glycopeptides (OR 5.9) remained
      significant. We confirmed our previous finding that LOS was associated with MRSA
      acquisition. Receipt of antibiotics correlated with reported literature. Novel
      associations were road trauma as a mechanism and laparotomy.

PMID- 15236856
TI  - Pulse-field gel electrophoresis typing of methicillin-resistant Staphylococcus
      aureus strains susceptible to aminoglycosides isolated from 1993 to 2002.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) susceptible strains to
      aminoglycosides (AS-MRSA) have been increasingly isolated in the Albert Cheneiver
      Hospital during the past 10 years. The aim of this study was first, to analyse
      the genotypes and the profiles of resistance to antibiotics and second to compare
      the AS-MRSA with the MRSA resistant to gentamicin (GR-MRSA) and with MRSA
      resistant to kanamycin and tobramycin, but susceptible to gentamicin (GS-MRSA),
      previously studied in our laboratory. All the AS-MRSA consecutively isolated from
      clinical samples (carriage isolates excluded) from 01/01/1993 to 31/12/2002 (33
      isolates) were typed by DNA macrorestriction. Their susceptibilities to other
      anti-staphylococcal drugs (erythromycin, lincomycin, tetracycline, rifampicin,
      fusidic acid and fosfomycin) were studied by the French standard disk method. The
      33 strains showed a heterogeneous resistance to oxacillin and fell into five
      phenotypes. The main phenotype (51.5% of the AS-MRSA strains) was susceptible to
      the six antibiotics studied. DNA macrorestriction defined 24 genotypes
      (percentage similarity <80%). Among them 16 genotypes contained only one strain
      each, and none contained more than three isolates. Conversely the comparison with
      GR-MRSA and GS-MRSA isolated during the same period showed that the strains were
      not closely linked. The diversity of our isolates showed that it was not an
      epidemic phenomenon, in contrast to the results of similar studies. Our findings
      may be explained by the patients coming mostly from different hospital units.
      This work indicates the need for further studies on the genome, to determine
      whether AS-MRSA have derived from strains that occurred before aminoglycosides
      came into clinical use.

PMID- 15236858
TI  - Arterial blood gas syringe safety device: does it present a greater hazard?

PMID- 15236857
TI  - The community prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in
      older people living in their own homes: implications for treatment, screening and
      surveillance in the UK.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) predominantly affects those
      over 65 years old. There may be a substantial pool of older people with MRSA in
      the community. We studied the prevalence in one London general practice,
      screening 258 older people living in their own home. MRSA (E-MRSA 15) was found
      in two participants (0.78%). Past history of MRSA was the only significant risk
      factor. The results of this and other studies suggest that national guidelines
      recommending early discharge for MRSA carriers have not resulted in widespread
      community acquisition amongst elderly people living in their own home. Community
      antibiotic policies for skin and soft-tissue infection do not require amendment.
      Patients with previous MRSA should be isolated and screened on admission
      especially to high-risk units.

PMID- 15236859
TI  - MRSA incidence as an indicator of infection control practices: do the results
      reflect the reality?

PMID- 15236860
TI  - Lithium suppressed Tyr-402 phosphorylation of proline-rich tyrosine kinase (Pyk2)
      and interactions of Pyk2 and PSD-95 with NR2A in rat hippocampus following
      cerebral ischemia.
AB  - It has been indicated that Pyk2/Src signaling pathway is involved in modulation
      of N-methyl-D-aspartate-type (NMDA) glutamate receptor activity. Lithium protects
      against glutamate-induced excitotoxicity in cultured neurons and in animal models
      of diseases. The neuroprotection against excitotoxicity afforded by lithium is
      time-dependent, requiring treatment for 6-7 days for maximal effect. In this
      study, we examined the time-course and the effect of lithium on Tyr-402
      phosphorylation of Pyk2 and Tyr-416 phosphorylation of Src as well as the
      association of Pyk2 and NMDA receptor subunit 2A (NR2A) mediated by postsynaptic
      density protein 95 kDa (PSD-95) in the condition of cerebral ischemia, which was
      induced by occlusion of the four vessels in Sprague-Dawley rats. At 6 h of
      reperfusion following 15 min of ischemia (I/R), the effects induced by chronic
      lithium were observed, including the decrease in enhanced Tyr-402 phosphorylation
      of Pyk2, the inhibition in increased Tyr-416 phosphorylation of Src and the
      attenuation in enhanced interactions of Pyk2 and PSD-95 with NR2A. Our results
      further suggest that the activated Pyk2 potentiates NMDA receptor function during
      transient brain ischemia followed by reperfusion and the above inhibition induced
      by lithium is likely to result in the inactivation of NMDA receptor and
      contributes to the neuroprotection against excitotoxicity.

PMID- 15236861
TI  - Overexpression of tau leads to the stimulation of neurite outgrowth, the
      activation of caspase 3 activity, and accumulation and phosphorylation of tau in
      neuroblastoma cells on cAMP treatment.
AB  - To explore changes to the tau molecule in Alzheimer's disease, we studied the
      effect of tau expression in stably transfected neuroblastoma x glioma hybrid
      NG108-15 cells (tau cells). Tau cells had a similar shape to, but more neurites
      than, wild type NG108-15 cells (wild type cells). When treated with cAMP, tau
      cells began to form neurites within 2h. After that, these neurites became longer
      and thicker than those of wild type cells. An accumulation and increased
      phosphorylation of tau were observed after 8 h and caspase 3 activity was
      increased after 4 h in tau cells, but not in wild type cells, upon treatment with
      cAMP. Caspase 3 activity was activated after the initiation of morphological
      change, and before the accumulation of tau in tau cells. Under these conditions,
      apoptotic cell death was not observed and tau was colocalized with tubulin.
      However, the accumulated tau molecules did not associate with tubulin and were
      dislocated around and in the nuclei of tau cells. These observations have
      implications for the cellular causes of Alzheimer's disease where the
      accumulation and mislocation of tau occur concomitant with neuronal degeneration.

PMID- 15236862
TI  - Neuronal gap junctions between intraglomerular mitral/tufted cell dendrites in
      the mouse main olfactory bulb.
AB  - In the mouse main olfactory bulb (MOB) gap junction-forming processes in
      glomeruli were analyzed by means of the serial electron microscopical
      reconstruction. Gap junctions were encountered between diverse types of dendritic
      processes and thus confirming our previous study on gap junctions in the rat MOB.
      Importantly, among more than 30 gap junctions examined in serial sections, we
      encountered 3 gap junctions made between mitral/tufted cell dendrites in the
      glomerulus. Then we must consider both direct coupling between mitral/tufted
      cells via gap junctions and indirect coupling between mitral/tufted cells via
      intervening interneuronal processes as suggested previously.

PMID- 15236863
TI  - Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of
      alcoholics.
AB  - Patients with alcoholism exhibit behavioral adaptations to ethanol such as
      tolerance, dependence, and addiction. Molecular mechanisms that underlie these
      altered behavioral responses to ethanol are largely unclear. We have performed
      oligonucleotide microarray analysis in postmortem prefrontal cortices of
      alcoholics. Among about 12,000 genes represented on microarray, a total of 79
      genes showed differential expression changes in alcoholics compared with control
      subjects, consisting of 54 up- and 25 down-regulated genes. Altered expressions
      in alcoholics were observed in genes having a wide range of biological functions.
      The remarkable findings were up-regulation of myelin-related genes and molecular
      chaperones in alcoholics. Among the genes identified, decreased expressions of
      NEFH and PCP4/PEP19 were further examined. NEFH encodes a component of
      neurofilament protein in neurons. PCP4/PEP19 encodes protein involved in calcium
      signaling and neuronal apoptosis. Observation of their down-regulations in
      alcoholics in microarray analysis was confirmed by real-time quantitative RT-PCR,
      and was also confirmed in the independent set of postmortem brains of alcoholics.
      The present results may provide some insights into understanding the mechanism of
      ethanol-induced altered behavioral responses at the molecular level.

PMID- 15236864
TI  - Time estimation during nocturnal sleep in human subjects.
AB  - It has been postulated that time estimation during nocturnal sleep in humans can
      be explained by an interval timing clock inside the brain. However, no systematic
      investigations have been carried out with respect to how the human brain
      perceives the passage of time during sleep. The brain mechanisms of over- or
      underestimation of time spent in sleep have not yet been clarified. Here, we
      carried out an experimental study in which 11 healthy volunteers participated in
      time estimation trials scheduled six times during 9 h nocturnal sleep periods,
      under carefully controlled conditions. The time estimation ratio (TER: a ratio of
      subjective passage of time to actual time interval) decreased significantly from
      the first to the sixth trial. Individual TER was positively correlated with slow
      wave sleep prior to the trial, while it was negatively correlated with REM sleep.
      Our results indicate that the human brain has an ability to estimate the passage
      of time during nocturnal sleep without referring to time cues, and that the
      accuracy of this function fluctuates from overestimation in the early hours of
      sleep to underestimation in the last hours of sleep.

PMID- 15236865
TI  - Birth-date dependent alignment of GABAergic neurons occurs in a different pattern
      from that of non-GABAergic neurons in the developing mouse visual cortex.
AB  - In the developing mouse cerebral cortex, gamma-aminobutyric acid (GABA)ergic
      neurons and non-GABAergic neurons arise in distinct places and migrate into the
      cortical plate (CP) via different pathways. Although the "inside-out" alignment
      of projection neurons in the cortex has been thoroughly analyzed, the pattern of
      interneuron alignment is not well understood. Herein, we show that in the
      postnatal day (P) 9.5 mouse visual cortex, GABAergic neurons born on embryonic
      day (E) 12.5 were distributed around two peak locations, mainly around layer V
      and also around layer II/III, while non-GABAergic neurons born on E12.5 were
      distributed around only one peak in layer VI. Both cell populations born on E15.5
      exhibited only one common peak distribution in layer II/III. The two peak
      locations of GABAergic neurons born on E12.5 still existed at P30. When the
      subtypes of GABAergic neurons were analyzed, calretinin-positive cells born on
      E12.5 were distributed in the cortex around one peak location near layer II/III,
      whereas somatostatin-positive E12.5 cells were distributed in the cortex around
      one peak location near layer V. These results suggest that the alignment of
      interneurons is regulated differently according to subtypes and from that of
      projection neurons having the same embryonic day of origin.

PMID- 15236866
TI  - Altered GABAB receptor immunoreactivity in the gerbil hippocampus induced by
      baclofen and phaclofen, not seizure activity.
AB  - The present study was performed to determine whether the effects induced by
      GABA(B) receptor-acting drugs would be related with the alteration in GABA(B)
      receptor expression in the hippocampus using Mongolian gerbil, a genetic epilepsy
      model. The distribution patterns of both GABA(B) receptor 1A/B and
      GABA(B)receptor 2 immunoreactivities were similarly detected in the hippocampi of
      normal and seizure-prone gerbils. Following baclofen (GABA(B) receptor agonist)
      or phaclofen (GABA(B) receptor antagonist) treatment, GABA(B) receptor
      immunoreactivities were decreased or increased by dose-dependent manners,
      respectively. Vigabatrin (GABA transaminase inhibitor) or 3-mercaptopropionic
      acid (GAD inhibitor) treatment did not affect GABA(B) receptor expressions. These
      findings suggest that GABA(B) receptor expression in the gerbil hippocampus may
      be altered by baclofen or phaclofen treatment.

PMID- 15236867
TI  - Extracellular histamine level in the frontal cortex is positively correlated with
      the amount of wakefulness in rats.
AB  - Histaminergic neurons have been strongly implicated in the regulation of
      wakefulness by activating cortical neurons. However, little is known about
      histamine release in the cortex during sleep-wake stages. In this study, we
      monitored the extracellular histamine level in the frontal cortex by in vivo
      microdialysis coupled with electroencephalogram and electromyogram recordings in
      freely moving rats. The histamine release was 3.8 times higher during wake
      episodes than during sleep episodes, being positively correlated (r = 0.845) with
      the time spent in wakefulness. These findings indicate that the histamine release
      in the cortex is strongly related to the sleep-wake cycle.

PMID- 15236868
TI  - Interactions of bradykinin and norepinephrine on rat cutaneous nociceptors in
      both normal and inflamed conditions in vitro.
AB  - Many inflammatory chemical mediators excite or sensitize nociceptors, which had
      led some researchers to believe that they may interact with each other to
      maintain a persistent painful state. We examined how the excitatory mediators
      norepinephrine (NE) and bradykinin (BK) interact, using single fiber recordings
      from cutaneous nociceptors. We observed that NE augmented the BK-induced response
      in both control and adjuvant-inflamed rats in a way different from NE-induced
      excitation in inflamed animals only. BK also tended to augment the NE-induced
      response (examined only in inflamed rats). Our results provide the first evidence
      that BK and NE synergistically interact on nociceptors.

PMID- 15236869
TI  - Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal
      tissues: a literature review.
AB  - Late complications are one of the major factors limiting radiotherapy treatment,
      and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in
      combination with radiotherapy for over half a century, either to maximise its
      effectiveness or in an attempt to treat late complications. In this latter case,
      retrospective trials and case reports are prevailing in literature. This prompted
      European Society for Therapeutic Radiotherapy and Oncology and European Committee
      for Hyperbaric Medicine to organise a consensus conference in October 2001,
      dealing with the HBO indications on radiotherapy for the treatment and prevention
      of late complications. This updated literature review is part of the documents
      the jury based its opinion on. A systematic search was done on literature from
      1960 to 2004, by only taking into account the articles that appeared in peer
      review journals. Hyperbaric oxygen treatment involving complications to the head
      and neck, pelvis and nervous system, and the prevention of complications after
      surgery in irradiated tissues have been studied. Despite the small number of
      controlled trials, it may be indicated for the treatment of mandibular
      osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant
      to conventional treatments and the prevention of osteoradionecrosis after dental
      extraction, whose level of evidence seems to be the most significant though
      randomised trials are still necessary. The other treatment methods are also
      outlined for each location.

PMID- 15236870
TI  - Sphincter preservation following preoperative radiotherapy for rectal cancer:
      report of a randomised trial comparing short-term radiotherapy vs. conventionally
      fractionated radiochemotherapy.
AB  - BACKGROUND AND PURPOSE: The aim was to verify whether preoperative conventionally
      fractionated chemoradiation offers an advantage in sphincter preservation in
      comparison with preoperative short-term irradiation. PATIENTS AND METHODS:
      Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration
      and with a lesion accessible to digital rectal examination were randomised into:
      preoperative 5x5Gy short-term irradiation with subsequent total mesorectal
      excision (TME) performed within 7 days or chemoradiation to a total dose of
      50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5
      fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were
      obliged to base the type of operation on the tumour status at the time of
      surgery. RESULTS: Between 1999 and 2002, 316 patients from 19 institutions were
      enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the
      radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P <
      0.001) among patients treated with chemoradiation compared with short-term
      schedule. For patients who underwent sphincter-preserving procedure, the surgeons
      generally followed the rule of tailoring the resection according to tumour
      downsizing; the median distal bowel margin was identical (2 cm) for both
      randomised groups. However, in the chemoradiation group, five patients underwent
      abdominoperineal resection despite clinical complete response. CONCLUSIONS:
      Despite significant downsizing, chemoradiation did not result in increased
      sphincter preservation rate in comparison with short-term preoperative
      radiotherapy. The surgeons' decisions were subjective and based on pre-treatment
      tumour volume at least in clinical complete responders.

PMID- 15236871
TI  - The influence of the boost technique on local control in breast conserving
      treatment in the EORTC 'boost versus no boost' randomised trial.
AB  - BACKGROUND AND PURPOSE: The EORTC Trial 22881/10882 investigating the role of a
      boost dose in breast conserving therapy demonstrated a significantly better local
      control rate with the higher radiotherapy dose, especially in women younger than
      50 years of age. This paper investigates the potential impact of the different
      boost techniques on local control and on fibrosis after breast conserving
      therapy. PATIENTS AND METHODS: From 1989 to 1996, 2661 patients were randomised
      to receive a boost dose of 16Gy to the primary tumour bed after microscopically
      complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost
      technique was left to the treating investigator. Treatment data were
      prospectively recorded as well as the clinical outcome in terms of local control
      and fibrosis. Sixty-three percent of the patients received a boost dose with fast
      electrons, 28% with photon beams and 9% with interstitial brachytherapy. RESULTS:
      At 5 years, local recurrences were seen in 74 of the 1635 patients who received
      an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a
      photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an
      interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast
      as well as at the primary tumour bed, as scored by the treating radiation
      oncologist, was similar in the three groups. CONCLUSIONS: Although the three
      groups are of a rather unequal size, the results of the interstitial boost seem
      similar in terms of fibrosis and at least as good in terms of local control,
      despite a lower treatment volume and a longer overall treatment time.

PMID- 15236872
TI  - Adjuvant radiotherapy for breast cancer: effects of longer follow-up.
AB  - BACKGROUND AND PURPOSE: Recent and large trials of adjuvant radiotherapy for
      breast cancer have shown an overall survival benefit in favour of radiotherapy.
      However, with longer follow-up the late lethal toxicity of radiotherapy might
      reduce the overall survival benefits. In this paper we investigate more deeply
      this hypothesis. PATIENTS AND METHODS: Overviews of the Early Breast Cancer
      Trialists' Collaborative Group provide uniform data on more than 50 unconfounded
      trials on adjuvant radiotherapy for early breast cancer. These data were
      published at regular intervals: 1987, 1990, 1995, and 2000. The odds ratios
      (death of any cause) were borrowed to compare the benefits of adjuvant
      radiotherapy between the early publications and the more mature data of the same
      trials. Statistical significance is calculated following logrank statistics. The
      comparison of odds ratios (radiotherapy versus surgery only) was done for the
      whole group of trials, for the older (patients accrual started in 1970 or
      earlier) and the more recent trials (patient accrual started after 1970), and for
      the large (>or=600 patients) and the small trials (<600 patients). RESULTS:
      Comparison of early with more mature data reveals that the odds ratios for
      overall survival remain stable as data become more mature. The analyses of
      trials' age and trials' size, as predictors of overall survival benefit, indicate
      that these factors become statistically more significant with increasing maturity
      of the trials. In the large recent trials an overall survival benefit due to
      radiotherapy (odds reduction) of 10, 10, 12 and 13%, respectively P<0.3, 0.2,
      0.005 and 0.00005 is found in the successive publications. The difference in
      survival benefit of radiotherapy between the group of large recent trials and
      group of old or small trials becomes more significant at the successive updates:
      10 via 9% and 12 to 13% (odds reductions), with respectively P=0.2, 0.2, 0.004
      and 0.00005. CONCLUSIONS: These results support the hypothesis that the survival
      benefit in the recent trials is an inherent characteristic of the recent and
      large trials, not influenced by follow-up duration. The effect of radiotherapy as
      performed in the large recent trials is clinically and statistically
      significantly different from the effect of radiotherapy in the old or small
      trials. As a consequence, predictions based on pooled data including old
      radiotherapy trials should not be extrapolated to modern radiotherapy.

PMID- 15236873
TI  - Patterns of care in radiotherapy of breast cancer in Austria 1985: data
      acquisition and comparison with data of US-PCS 1983.
AB  - PURPOSE: In Austria, a Patterns of Care Study (PCS) has been conducted to
      evaluate the standards of practice for breast cancer patients. The year 1985 was
      selected in order to establish a base data set. MATERIALS AND METHODS: At all
      nine radiation therapy facilities active in patient treatment in 1985, ten
      patients charts were randomly selected and reviewed. Evaluation of the
      radiotherapeutic standards was the principal purpose, however, surgical and
      histopathological parameters were also considered. RESULTS: Results of the
      Austrian PCS (including 90 patients) were compared with the "1983 Patterns of
      Care Process Survey for Definitive Breast Irradiation" performed in 1983 in the
      U.S. (including 191 patients). Documentation of pathologic tumour size (83% vs.
      73%), histologic tumour subtype (99% vs. 97%) and microscopic margin analysis
      (60% vs. 51%) showed comparable results. Technical equipment was obviously quite
      different in the two countries, cobalt therapy was used in 25% in the US-PCS
      compared to 71% in the Austrian PCS. A clear difference also was obtained
      concerning the use of wedges for tangential breast/thoracic wall fields (64% vs.
      21%) and the frequency of portal films (93% vs. 26%). CONCLUSIONS: Comparing both
      PCS studies, we found overall many similarities. Differences could be obtained in
      the quality level of radiation treatment, as for example use of wedges for
      tangential fields and the number of portal films. In a next step, a further
      Austrian PCS is planned to compare the Austrian base data from 1985 with quality
      standards from 1993 and 2001.

PMID- 15236874
TI  - Breathing adapted radiotherapy of breast cancer: reduction of cardiac and
      pulmonary doses using voluntary inspiration breath-hold.
AB  - BACKGROUND AND PURPOSE: Adjuvant radiotherapy of breast cancer using wide
      tangential photon fields implies a risk of late cardiac and pulmonary toxicity.
      This CT-study evaluates the detailed potential dosimetric consequences of
      applying breathing adapted radiotherapy (BART), and the feasibility of a
      monitored voluntary breath-hold technique for right-sided as well as for left
      sided tumours. PATIENTS AND METHODS: After breast-conserving surgery, 16 patients
      were CT-scanned in distinct respiratory phases using the varian real-time
      position management system for the monitoring of respiratory anterioposterior
      chest wall excursion. Each patient underwent three scans: during free breathing
      (FB), voluntary expiration breath-hold (EBH) and voluntary deep inspiration
      breath-hold (DIBH). For each scan, an optimised treatment plan was designed with
      conformal tangential fields encompassing the clinical target volume (CTV) of the
      breast and ipsilateral internal mammary nodes, and an anterior supraclavicular
      field. RESULTS: Breath-hold was well accepted by the patients, with a median
      duration of 24 s for both EBH and DIBH. The mean anterioposterior chest wall
      excursions were 2.5, 2.6 and 4.1 mm during FB, EBH and DIBH, respectively. During
      EBH, the mean front chest wall position was 2.7 mm posterior to its mid-FB
      position, and during DIBH 12.6 mm anterior to its mid-FB position. For right
      sided tumours, the median ipsilateral relative lung volume receiving >50% of the
      prescribed CTV dose was 39, 49 and 32% for FB, EBH and DIBH, respectively. For
      left-sided tumours, the corresponding percentages were 37, 46 and 31%. The median
      heart volume receiving >50% of the prescription dose was reduced from 8% for FB
      to 1% for DIBH, and the median left anterior descending coronary artery volume
      was reduced from 54 to 5%. CONCLUSIONS: Irradiated cardiac volumes can
      consistently be reduced for left-sided breast cancers using DIBH for wide
      tangential treatment fields. Additionally, substantial dose reductions in the
      lung are observed for both right- and left-sided tumours.

PMID- 15236875
TI  - Accuracy of ultrasound in localization of breast boost field.
AB  - BACKGROUND AND PURPOSE: To prospectively compare diagnostic ultrasound to the
      'gold standard' of surgical clips for localization of the lumpectomy site for
      electron boost irradiation. PATIENTS AND METHODS: Consecutive breast cancer
      patients referred following lumpectomy underwent diagnostic ultrasound in
      radiation treatment position 21-100 days post-surgery. All patients had 3-6
      surgical clips defining the excision cavity. The site was marked on the skin and
      depth was measured. Target depth was the deepest aspect of the cavity plus a 1 cm
      deep margin. Treatment fields were prescribed with a 2 cm margin on the cavity,
      and electron energy was chosen to cover the target depth. Surgical clip position
      was assessed on orthogonal simulator films. RESULTS: Localizations were performed
      in 54 breasts (52 women). The mean interval post-surgery was 53 (SD 17) days.
      Overall, 35/54 (65%) of localizations were adequate, 15/54 (28%) were marginal
      and 4/54 (7%) were inadequate. Regression showed that lower patient weight (r=
      0.37, P=0.006) predicted adequacy of localization, with better accuracy in
      lighter women. CONCLUSIONS: The accuracy rate for ultrasound exceeds the 20-50%
      reported for clinical localization. Diagnostic ultrasound may be used to improve
      the accuracy when surgical clips are not present.

PMID- 15236876
TI  - Post-irradiation dietary vitamin E does not affect the development of radiation
      induced lung damage in rats.
AB  - The purpose of this study was to investigate whether application of post
      irradiation vitamin E, an anti-oxidant, could prevent the development of
      radiation induced lung damage. Wistar rats were given vitamin E enriched or
      vitamin E deprived food starting from 4 weeks after 18Gy single dose irradiation
      of the right thorax. Neither breathing frequencies nor CT density measurements
      revealed differences between the groups. It is concluded that post-irradiation
      vitamin E does not influence radiation-induced fibrosis to the lung.

PMID- 15236877
TI  - Non-metastatic stage IV nasopharyngeal carcinoma patients: analysis of the
      pattern of relapse and survival.
AB  - BACKGROUND AND PURPOSE: The objective of this study is to analyze the mode of
      recurrence patterns and survival of our 96 non-metastatic stage IVA and IVB
      nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A total of 234
      previously untreated, histologically confirmed non-metastatic NPC patients were
      treated in our department between 1993 and 2001. Among them 96 patients (41%)
      were staged as IVA or B disease. All patients were uniformly staged using the
      fifth edition of AJCC/UICC staging system. There were 76 male and 20 female
      patients. Their ages ranged from 9 to 72 years (median age: 43.5).
      Histopathological diagnosis was WHO 2 and 3 in 89 (93%) patients. All patients
      were treated with external radiotherapy and 77 out of 96 patients (80%) with
      stage IV disease received either concomitant or neoadjuvant cisplatin based
      combined chemotherapy regimens. Median follow-up time was 30 months (range: 4-101
      months). RESULTS: At the time of this analysis, 60 (62%) patients were alive and
      48 of them were free of disease. Local recurrence rate was found to be
      significantly higher in stage IVA patients (28 vs. 11%, P=0.02) and distant
      metastasis rate was significantly higher in stage IVB patients (40 vs. %8,
      P=0.0001). The 3 year overall (OS), disease free (DFS), loco regional relapse
      free (LRRFS) and distant metastasis free survival (DMFS) rates were 71, 74, 77
      and 94% for stage IVA and 60, 46, 77 and 58% for stage IVB patients,
      respectively. Three year LRFS rates for stage IVA and IVB were 77 and 89%,
      respectively (P=0.1). Age older than 40 years was found to be statistically
      significant adverse prognostic factor both for OS (P=0.01) and LRRFS (P=0.005) in
      univariate analysis. Advanced N status was an unfavorable prognostic factor both
      for OS (P=0.03), DFS (P=0.0004) and DMFS (P=0.0003). DMFS was adversely affected
      by the presence of cranial nerve palsy at diagnosis (P=0.01), advanced T status
      (P=0.03) and advanced N status (P=0.0003). In univariate analysis treatment with
      chemotherapy was found to be an unfavorable prognostic factor for DMFS (P=0.02).
      According to the multivariate analysis, older age (>40 year of age) was a
      significant independent prognostic factor for OS (P=0.02), DFS (P=0.05) and LRRFS
      (P=0.01). Patients with advanced N status had worse OS (P=0.03), DFS (P<0.0001)
      and DMFS (P=0.07). Patients treated with chemotherapy as an adjuvant to
      radiotherapy had tended to have a better DFS (P=0.04). CONCLUSIONS: The local
      relapse was the major cause of failure in patients with stage IVA disease, and
      distant metastasis was the predominant treatment failure in stage IVB patients.
      While stage IVA patients may benefit more intensive local treatment strategies,
      stage IVB patients definitely need more systemic treatment.

PMID- 15236878
TI  - Sensory neural hearing loss after concurrent cisplatin and radiation therapy for
      nasopharyngeal carcinoma.
AB  - Sensory neural hearing loss (SNHL) was evaluated in the patients who were treated
      with concurrent chemoradiation therapy for nasopharyngeal carcinoma. Ten from 48
      ears showed persistent SNHL. Radiotherapy techniques, radiation dose to inner ear
      and post-treatment otitis media were significant predicting factors for SNHL.

PMID- 15236879
TI  - Undifferentiated sinonasal carcinoma may respond to single-fraction boron neutron
      capture therapy.
AB  - A large, rapidly progressing, unresectable undifferentiated sinonasal head and
      neck carcinoma regressed rapidly following single fraction boron neutron capture
      therapy (BNCT). The main toxicity consisted of mucositis lasting for a few days.
      The quality of life improved and was excellent until tumour recurrence 6 months
      after the date of BNCT.

PMID- 15236880
TI  - Cancer mortality after radiotherapy for a skin hemangioma during childhood.
AB  - BACKGROUND AND PURPOSE: A cohort study was performed as part of a European
      Radiation Protection Program to investigate the carcinogenic effect of treatment
      with ionizing radiation in early childhood. This paper presents mortality after
      radiotherapy in this cohort. PATIENTS AND METHODS: The cohort comprised 7037
      patients under 15 years of age treated for a skin hemangioma between 1940 and
      1973 at the Institut Gustave-Roussy, among whom 4940 received radiotherapy. The
      vital status and causes of death were obtained as well as the mortality rates in
      the general French population. External and internal analyses were performed.
      Standardized mortality ratio (SMR) and relative risk (RR) variations according to
      exposure to radiotherapy or not and the type of treatment were studied. RESULTS:
      During the 1969-1997 follow-up period, 16 cohort patients died of cancer, 14
      after radiotherapy. A non-significant excess of cancer-related mortality was
      observed for irradiated patients as compared to the general population (SMR=1.53;
      95% CI=0.86-2.48). Treatment with (226)Ra seemed to play a significant role
      (RR=2.53; 95% CI=0.84-7.07) compared to no radiotherapy. CONCLUSION: This study
      suggests an excess risk of cancer-related mortality in patients treated during
      early childhood with radiotherapy for skin hemangioma, and especially with
      (226)Ra. These patients need to be followed up in the future.

PMID- 15236881
TI  - Adjuvant inhibition of the epidermal growth factor receptor after fractionated
      irradiation of FaDu human squamous cell carcinoma.
AB  - BACKGROUND AND PURPOSE: Experiments performed by others have shown that
      inhibition of EGFR before and after single dose irradiation prolonged growth
      delay and improved local tumour control. This suggests that adjuvant EGFR
      inhibition can inactivate clonogens that survived irradiation. To test this
      hypothesis local tumour control was investigated after fractionated radiotherapy
      and adjuvant EGFR-TK inhibition. MATERIALS AND METHODS: FaDu hSCC xenografts were
      irradiated with 30 fractions in 6 weeks with total doses of 30-100Gy. After the
      end of fractionated irradiation, BIBX1382BS was administered daily orally over a
      time period of 75 days. Tumour volumes were determined two times per week, the
      volume doubling time during adjuvant treatment was calculated for progressing and
      recurrent tumours. Local tumour control was investigated 120 days after end of
      irradiation. RESULTS: Adjuvant BIBX1382BS significantly reduced the tumour growth
      rate but did not improve local tumour control. The TCD(50) values were 66.1Gy
      (95% C.I.: 59; 73Gy) after adjuvant BIBX1382BS treatment and 67.9Gy (61; 75Gy)
      for control tumours (P=0.9). CONCLUSIONS: These data indicate that, although
      growth of recurrent tumour cells after irradiation is dependent on the EGFR
      pathway, tumour cells retain their clonogenic potential despite of EGFR
      inhibition. The results imply also that a decreased tumour growth rate does not
      necessarily allow conclusions on enhanced inactivation of clonogenic cells when
      antiproliferative drugs are combined with radiation.

PMID- 15236882
TI  - Clonogenic survival and cytokinesis-blocked binucleation of skin fibroblasts and
      normal tissue complications in soft tissue sarcoma patients treated with
      preoperative radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate the clonogenic and cytokinesis-blocked assays
      in skin fibroblast cultures for their utility as tools for predicting normal
      tissue responses in soft tissue sarcoma (STS) patients treated with preoperative
      radiotherapy. PATIENTS AND METHODS: Dermal fibroblast strains were established
      from skin biopsies of 26 STS patients who received preoperative radiotherapy.
      Cultures were subjected to the colony forming and cytokinesis-blocked assays
      after low (approximately 0.02 Gy/min) dose-rate 60Co -irradiation. Fibroblast
      radiosensitivity was expressed as the dose for 1% clonogenic survival, D0.01,
      based on colonies/clusters with >or=10 cells. Fibroblast proliferative capability
      was represented by binucleation index (BNI) and genomic damage was expressed in
      terms of micronucleus frequency. Wound healing complications (WHC) and
      subcutaneous fibrosis were the clinical endpoints examined. The ability of each
      in vitro parameter to detect patients at high risk of a given normal tissue
      complication was assessed using receiver operating characteristic (ROC) analysis.
      RESULTS: While fibroblasts from patients without WHC were marginally more
      radiosensitive than fibroblasts from patients with WHC (P=0.08), the reduction in
      BNI following a dose of 2.4 Gy was significantly higher in strains from patients
      without WHC compared to those from patients with WHC (P=0.01). The area under the
      ROC curve (c-index) is indicative of the power of discrimination of D0.01 and BNI
      for WHC, and was found to be 0.68 and 0.79, respectively. Subcutaneous fibrosis
      was not associated with D0.01 (rs=0.09, P=0.66) and the percent reduction in BNI
      after 2.4 Gy (rs=-0.19, P=0.36). Micronucleus frequency did not reflect
      differences in normal tissue responses. CONCLUSION: These data suggest that it is
      the ability of fibroblasts to undergo one-three divisions in vitro following
      radiation treatment that may reflect the development of wound healing morbidity
      or subcutaneous fibrosis in this population of patients.

PMID- 15236883
TI  - The effect of fraction time in intensity modulated radiotherapy: theoretical and
      experimental evaluation of an optimization problem (the real conclusions): in
      regard to Mu et al. Radiotherapy on Oncology 2003; 68: 181-87.

PMID- 15236885
TI  - Connexin 26 mutations in nonsyndromic autosomal recessive hearing loss: speech
      and hearing rehabilitation.
AB  - OBJECTIVE: Hearing loss is the most common form of sensory impairment, with
      approximately one infant/1000 born with profound congenital deafness. A pre
      lingual bilateral sensorineural hearing impairment poses a substantial problem as
      it negatively impacts on the subject's ability to conduct a normal social life.
      The aim of the study was to observe, in a group of children affected by pre
      lingual non-syndromic autosomal recessive hearing impairment: (1) the role of the
      possible mutation of connexin 26 in the pathogenesis of the hearing loss; (2) the
      audiological and clinical aspects of the hearing impairment; (3) therapy to be
      adopted for the different patients. METHODS: The study was carried out on 39
      patients, 16 males and 23 females, aged between six and 17 years (mean 12 years),
      affected by non syndromic congenital deafness, presumably hereditary, referred to
      the out-patients audiology clinic for children of the Department of
      Otolaryngology of the Federico II University of Naples. RESULTS: Our study
      conducted on 39 children with pre-lingual bilateral sensorineural autosomal
      recessive deafness showed as follows: (I) from a molecular perspective: an
      incidence of 41% in the cases studied of mutations in the encoding of the
      connexin 26 gene; a prevalence in our case study of the 35delG mutation (69%).
      (II) The characteristics of the hearing impairments in the children studied were
      homogeneous, regardless of the presence or absence of a connexin 26 mutation: the
      hearing impairment was pre-lingual bilateral sensorineural, the impairment often
      involved mainly the high frequencies, but, especially in the severe forms an
      involvement of all the frequencies was not rare; the hearing impairments were
      symmetrical and non progressive in time. (III) The results of the application of
      prosthesis and thereafter rehabilitative language therapy are generally
      satisfactory but correlated of course to the severity of the hearing loss.
      CONCLUSION: In conclusion, we hope that further developments in the research on
      genetic hearing impairments will promptly result in advances in clinical
      practice.

PMID- 15236886
TI  - Effect of intranasal triamcinolone acetonide on bronchial hyper-responsiveness in
      children with seasonal allergic rhinitis and comparison of perceptional nasal
      obstruction with acoustic rhinometric assessment.
AB  - OBJECTIVE: Many patients with allergic rhinitis (AR) have bronchial hyper
      responsiveness (BHR), and seasonal variation of BHR has been demonstrated in
      these patients. We aimed to investigate how BHR in children with seasonal AR is
      modified by triamcinolone acetonide aqueous nasal spray (TANS) therapy during the
      pollen season. A secondary aim was to assess the efficacy of TANS on nasal
      congestion by acoustic rhinometry and symptom scores. METHODS: A total of 34
      children aged 7-18 years with grass pollen-induced AR and 18 age and sex-matched
      healthy controls were included in study. The patients were divided into the
      following two subgroups: 22 patients who had AR only; and 12 patients who had AR
      and asthma. All of them had a baseline BHR (PC20FEV1 methacholine < 8mg/ml). All
      patients received 220 microg TANS once daily for 4 weeks following a 1-week run
      in period. Nasal patency was measured by acoustic rhinometry and patients
      recorded their nasal obstruction scores in a diary. RESULTS: There was no
      significant difference at baseline pulmonary function test parameters between the
      patients and the healthy control children. None of the control subjects had BHR.
      Asthmatic children with AR had significantly reduced baseline PC20FEV1 when
      compared with the AR only group [mean +/- S.E.M., (1.60 +/- 0.57 mg/ml versus
      2.93 +/- 0.42 mg/ml, P = 0.021)]. The mean PC20FEV1 values increased slightly at
      the end of treatment in both group (from 1.60 +/- 0.57 mg/ml to 3.25 +/- 1.11 and
      from 2.93 +/- 0.42 mg/ml to 3.93 +/- 1.41 mg/ml), but the change was not
      statistically significant. TANS produced substantial symptomatic recovery in
      nasal obstruction according to patients' daily diary assessments, and
      significantly improved all objective acoustic rhinometry parameters. CONCLUSIONS:
      Once-daily intranasal TANS 220 microg effectively controlled nasal obstruction in
      children with seasonal AR according to subjective and objective assessments, and
      blocked the increase in BHR to methacholine after high-load natural pollen
      exposure. There was no correlation between patients' own subjective assessment of
      nasal obstruction and objective acoustic rhinometric assessment.

PMID- 15236887
TI  - Device fixation and small incision access for pediatric cochlear implants.
AB  - OBJECTIVE: Small incision cochlear implant surgery has been advocated to improve
      cosmesis and reduce post-operative morbidity. However, with standard small
      incision techniques, it is not possible to securely fix the device in place. This
      risks displacement of the device, particularly in active children. This paper
      describes the development of a technique which combines secure ligature tie-down
      of the device with a small incision. METHODS: A 25 mm skin incision is positioned
      close to the hair line behind the pinna. Specially modified instruments are used
      to drill a well for the receiver-stimulator pedestal down to dura. In younger
      children, ligature tie-down holes are drilled through the calvarium. Alternative
      methods for older children are described. Outcome data are reviewed. RESULTS: One
      hundred children have been implanted with the small incision technique. No
      complications have occurred related to the current technique (maximum follow up
      22 months). In five cases, during early development of the technique, the
      receiver-stimulator device was only secured by a tight periosteal pocket. In one
      of these cases, the device became dislodged from its well. CONCLUSIONS: Secure
      fixation of the receiver-stimulator unit of a cochlear implant is particularly
      important in children because of the risk of displacement with trauma. The
      conventional means of securing the device with a ligature has been combined with
      modified small incision techniques to meet this requirement successfully.

PMID- 15236888
TI  - The effect of fusafungine on post-operative pain and wound healing after
      pediatric tonsillectomy.
AB  - OBJECTIVE: To investigate the effect of fusafungine spray on pain and healing
      process after pediatric tonsillectomy. METHODS: Sixty children with ages between
      4 and 14 years underwent tonsillectomy or adenotonsillectomy. The patients were
      randomly divided into three groups and each group consisted of 20 patients. Group
      1 was treated with antibiotic (amoxicillin-clavulanic acid) plus analgesic
      (acetaminophen), group 2 was treated with fusafungine plus analgesic
      (acetaminophen) and group 3 was treated with only fusafungine. The average ages
      were 7.8 + 3.4, 6.6 + 2.9, and 8.2 + 3.7 for groups 1, 2, and 3, respectively.
      Clinical evaluations were made after the operation on the 1st (T1), 3rd (T3), 7th
      (T7), 10th (T10), and 14th days (T14). RESULTS: There was no significant
      difference in post-operative pain between study groups on the post-operative 1st,
      3rd, and 7th days (P > 0.05), a statistically significant difference was present
      between groups 1 and 3, and groups 1 and 2 on the post-operative 10th and 14th
      day (P = 0.018 and 0.037, respectively). Pain was less in groups 2 and 3 than in
      group 1 on the 10th and 14th day. Also there was a significant difference in
      healing time of the tonsillary beds between groups 1 and 2, and groups 1 and 3 on
      the 10th and 14th post-operative day (P = 0.031 and 0.001, respectively). Healing
      was better in groups 2 and 3 than in group 1 on the 10th and 14th day.
      CONCLUSION: Fusafungine administration after tonsillectomy was found to be
      beneficial on post-operative pain and wound healing of tonsillary beds in
      pediatric population.

PMID- 15236889
TI  - Parental decision-making in considering cochlear implant technology for a deaf
      child.
AB  - OBJECTIVES: Advances in cochlear implant (CI) technology have increased the
      complexity of treating childhood deafness. We compare parental decision-making,
      values, beliefs, and preferences between parents of eligible and ineligible
      children in considering cochlear implants. METHODS: Surveys were obtained from 83
      hearing parents of deaf children. A subset of 50 parents also underwent semi
      structured interviews. Nine hypothetical outcomes, ranging from mainstream
      success to poor mainstream outcome were created to measure parents' overall
      preferences and preference for specific outcomes for their child who is deaf.
      RESULTS: Among parents of eligible children (n = 50), approximately 2/3
      considered implantation (n = 33). The other 1/3 did not consider implantation.
      Parents who were eligible but did not consider implantation placed significantly
      lower priority on mainstream success over bilingual success (P < 0.03), and on
      the child's ability to speak versus sign (P < 0.02). They also showed
      significantly higher concerns on the cost of services in general and on the
      availability of resources offered at the local school district (both P > 0.05).
      Parents of ineligible children (n = 30) rarely considered implantation, even if
      they showed similar aspirations in mainstream outcomes (P = 0.003). Semi
      structured interview data supported these findings. CONCLUSIONS: The decision to
      consider cochlear implantation is strongly influenced by the eligibility and by
      professionals' recommendations. However, for some parents, the decision goes
      beyond eligibility and is determined by parental preferences, goals, values, and
      beliefs. This highlights the importance of careful audiologic evaluation and
      professionals' awareness of and sensitivity to parental goals, values, and
      beliefs in evaluating the child's candidacy.

PMID- 15236890
TI  - Objectivating nasality in healthy and velopharyngeal insufficient children with
      the Nasalance Acquisition System (NasalView). Defining minimal required speech
      tasks assessing normative values for Dutch language.
AB  - OBJECTIVES: (1) To define normative nasalance data for Dutch language with "the
      NasalView System", and obtain a reference for normality when nasality is
      evaluated in children. (2) To investigate the minimal number of required speech
      tasks for a reliable nasalance measurement. METHODS: 55 children (30 normal and
      25 velopharyngeal insufficient), aged between 4 and 11 were included. All
      children had to read or repeat two Dutch passages ((one with a normal amount of
      nasal consonants (normal passage) and one with none (nonnasal passage)). Further,
      one normal and one velopharyngeal insufficient subject read a passage in
      repetition to test the NasalViews reproducibility: (1) For both passages, group
      means (GM) and standard deviations (S.D.) were used to compute "pathological
      nasalance boundaries" [GM +/- (2 x S.D.)], in combination with the coefficient of
      variation (CV), sensitivity, specificity and positive predictive values. (2) With
      ANOVA all sentences within each passage were tested for significant differences
      in nasalance. RESULTS: (1) The pathological boundaries were 28.6-41.4% (GM: 35.0)
      and 21.4-34.7% (GM: 28.1), for the normal and nonnasal passage, respectively. For
      the normal passage a sensitivity of 96%, a specificity of 93% and a positive
      predictive value of 92% was computed. For the nonnasal passage these parameters
      were 96, 95 and 96%, respectively. Intra subject CVs of 3.6% (normal subject) and
      1.5% (VI subject) showed good reproducibility of measurements. (2) Within the
      normal passage only the third sentence was significantly different in nasalance,
      compared to the entire passage (31.2% versus 35.0%). Within the nonnasal passage
      the second and fifth sentences were significantly different (23.8 and 24.8%
      versus 28.1%). However, the individual nonsignificantly different sentences
      showed a higher variation in nasalance compared to the entire passages.
      CONCLUSIONS: The NasalView System seems to be reliable and quantifies valid
      nasalance values when nasality is evaluated. Within both passages high levels of
      sensitivity, specificity and positive predictive values were obtained. The
      nonnasal passage discriminates slightly better for hypernasal speech. For the
      most reliable nasalance measurements, the entire passage should be used.

PMID- 15236891
TI  - Can post-adenotonsillectomy morbidity be reduced by intravenous 24 h hydration in
      pediatric patients following adenotonsillectomy?
AB  - OBJECTIVE: To determine the benefit of 24 h intravenous hydration for pediatric
      postoperative adenotonsillectomy patients. STUDY DESIGN: A prospective,
      randomized controlled clinical study. METHODS: The study is consisting of two
      groups of pediatric patients following adenotonsillectomy performed in a
      university hospital. One group received 24 h IV hydration at hospital while the
      other did not have IV hydration. Chi-square and two-tailed unpaired Student's t
      tests were used to compare the two independent groups. P < 0.05 was accepted as
      statistically significant. RESULTS: Although the postoperative parameters such as
      nausea, fever, vomiting, odor, bleeding, otalgia and trismus were not
      statistically different between the two groups based on chi-square analysis (P >
      0.05), a significant pain-relieving effect was seen in hydration group after the
      second day (P < 0.05). There were no complications associated with intravenous
      hydration. CONCLUSION: Results of the current study suggest that 24 h IV
      hydration can reduce postoperative pain in late postoperative period following
      adenotonsillectomy in children but does not offer much advantage over without IV
      hydration therapy based on a number of other parameters. Furthermore, it seems to
      be cost effective, safe and easy and even these are encouraging for further
      studies in the future.

PMID- 15236893
TI  - The sizes of internal jugular veins in Turkish children aged between 7 and 12
      years.
AB  - OBJECTIVE: In this study, we aimed at searching for internal jugular vein (IJV)
      diameters in Turkish children in order to learn about anatomic details of IJV
      diameters and to supplement the diagnostic criteria in vascular pathologies such
      as phlebectasia. METHODS: A total of 92 children within the age range of 7-12
      years were included in this study. In order to provide a consistent anatomical
      landmark in all subjects, all of the children were imaged by ultrasonography
      (USG) at the level of the cricoid cartilage. The measurements consisted the
      maximal antero-posterior (AP) and transverse (T) cross-sectional internal
      diameters of the internal jugular veins during both regular breathing and
      Valsalva maneuver. For the statistical purposes, the following analyses were
      performed: the relationship between the IJV diameters obtained at rest and those
      obtained during Valsalva maneuver, with the paired t-test; the relationship
      between the age groups and the IJV diameters, with the unpaired test. The
      significance was set at P < 0.05. RESULTS: During regular breathing, the mean
      transvers diameters of the right and left IJVs were 11.26 and 10.01 mm,
      respectively, while they were 16.28 and 13.61 mm during straining phase of the
      Valsalva maneuver. The mean antero-posterior diameters of the right and left IJVs
      before and during Valsalva maneuver were 7.64 and 6.8 mm versus 11.53 and 9.84
      mm. The IJV diameters were larger on the right side than those on the left and
      also there were significant increases in the diameters by Valsalva maneuver.
      CONCLUSION: As a result, in this study performed among Turkish children aged
      between 7-12 years, it was shown that there was no correlation between the IJV
      diameters and the age groups (P > 0.05), while there was a significant increase
      in the IJV diameters on Valsalva maneuver (P < 0.05). We think that the results
      we obtained in this study may be useful and important for comparison in the
      patients with phlebectasia and also for the required knowledge of the anatomic
      details in medical interventions performed through IJV. However, since children
      aged between 0 and 6 years were not included in this study and the lack of
      relation found in our study may not be the same among 0-6 years, a further study
      is needed to show any interrelationship between former age group and size.

PMID- 15236892
TI  - The role of oxidants and antioxidants in chronic tonsillitis and adenoid
      hypertrophy in children.
AB  - OBJECTIVE: To determine the possible role of oxidants and antioxidants in the
      pathogenesis of chronic tonsillitis (CT) and adenoid hypertrophy (AH) in
      children. METHODS: Randomized, prospective, controlled. The study group was made
      up of children with chronic tonsillitis and adenoid hypertrophy who are to
      undergo tonsillectomy and adenoidectomy. The control group was constructed with
      otherwise healthy children with normal ENT examination. The blood levels of
      antioxidants (retinol, beta-carotene, alpha-tocopherol, laycopene, ascorbic acid,
      superoxide dismutase, glutathione peroxidase, GSH) and peroxidation products
      (malondialdehyde) were determined before and 1 month after the operation in the
      study group and once only in the control group. These antioxidants and
      peroxidation products were also measured in the tonsil and adenoid tissue that
      were obtained during operation. RESULTS: In the study group, the blood levels of
      antioxidants and oxidant before and after the operation were significantly
      different when compared to the control group (P < 0.05). In the study group, the
      blood antioxidant levels increased and oxidant level decreased significantly
      after the operation (P < 0.05). These levels after the operation never reached
      those of the control group. CONCLUSIONS: Oxidants and antioxidants played a
      significant role in the pathogenesis of chronic tonsillitis and adenoid
      hypertrophy in children. These children are under significant oxidative stress.
      Tonsillectomy and adenoidectomy significantly decreased the oxidative stress in
      these patients, but could not normalize it completely. Further studies are
      necessary to evaluate their possible therapeutic role in preventing recurrent
      tonsillitis and treating postoperative patients to help normalize their blood
      levels of antioxidants.

PMID- 15236894
TI  - Clinical and genetic linkage analysis of a large Venezuelan kindred with Usher
      syndrome.
AB  - OBJECTIVE: To undertake a comprehensive investigation into the very high
      incidence of congenital deafness on the Macano peninsula of Margarita Island,
      Venezuela. METHODS: Numerous visits were made to the isolated island community
      over a 4-year-period. During these visits, it became apparent that a significant
      number of individuals complained of problems with hearing and vision.
      Socioeconomic assessments, family pedigrees and clinical histories were recorded
      on standard questionnaires. All individuals underwent thorough otolaryngologic
      and ophthalmologic examinations. Twenty milliliters of peripheral venous blood
      was obtained from each participant. A genome-wide linkage analysis study was
      performed. Polymorphic microsatellite markers were amplified by polymerase chain
      reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to
      separate fragments and LOD scores were calculated by using published software.
      RESULTS: Twenty-four families were identified, comprising 329 individuals, age
      range 1-80 years, including 184 children. All families were categorized in the
      lower two (least affluent) socioeconomic categories. A high incidence of
      consanguinity was detected. Fifteen individuals (11 adults, 4 children) had
      profound congenital sensorineural hearing loss, vestibular areflexia and
      retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers
      D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin
      VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are
      consistent with a diagnosis of Usher syndrome 1B for those with hearing and
      vision problems. CONCLUSIONS: We report 15 Usher syndrome 1B individuals from a
      newly detected Latin American socio-demographic origin, with a very high
      prevalence of 76 per 100,000 population.

PMID- 15236895
TI  - Prevalence of otitis media with effusion in first and second grade primary school
      students and its correlation with BCG vaccination.
AB  - OBJECTIVE: The object of this study was to determine the prevalence of otitis
      media with effusion (OME) in first and second grade primary school students, to
      analyze the causes of the difference in the prevalence, to define the effect of
      OME on the academic performance of the children and to investigate a correlation
      between the prevalence of OME and Bacillus Calmette-Guerin (BCG) vaccination.
      STUDY PLAN AND METHODS: The study was conducted during the September-November,
      2002 period in Elazig. A total of 3675 clinically healthy primary school children
      attending primary schools in the central district of Elazig, living in the same
      region and of a similar socioeconomic status and age group were included in the
      study. Of the 3675 children, 2042 were in their first and 1633 in their second
      grade of primary school. The routine ear-nose and throat examinations of the
      children were carried out at their schools by the same medical team. The
      tympanometric test was performed in children diagnosed with OME following
      otoscopic examination. A scale measuring the academic performance of the children
      was developed. This scale was filled in by the student's teachers prior to
      physical examination. RESULTS: OME was diagnosed in 64 out of 2042 (3.1%) first
      grade and in 25 out of 1633 (1.5%) second grade students. The difference between
      the percentages of OME in first and second grade students was statistically
      significant (P < 0.05). The frequency of other ear-nose and throat pathologies
      accompanying OME was similar to those in children without OME. There was no
      statistically significant difference between the academic performances of
      children with and without OME (P > 0.05). CONCLUSION: The analysis of risk
      factors for OME revealed no difference between first and second grade students.
      The reason for the difference in the prevalence of OME between first and second
      grade students may be the positive effect on the immune system of the BCG vaccine
      which had been administered to the second grade students 4 months previously.

PMID- 15236896
TI  - Klippel-Trenaunay-Weber syndrome with labyrinthine bony overgrowth and mixed
      hearing loss, a case report.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by a
      triad of (1) capillary malformations, (2) venous malformations, and (3) soft
      tissue or bony hypertrophy. There exists one report of a patient with KTS and an
      associated sensorineural hearing loss. We describe an adolescent girl with KTS
      and AV fistulas who was found to have a bony overgrowth extending from the
      cochlea into the middle ear cavity and an ipsilateral mixed hearing loss. In both
      of these patients, there were obvious KTS deformities involving the face. We
      suggest conducting hearing screening in patients with KTS and obvious head
      involvement.

PMID- 15236897
TI  - Coexistence of choanal atresia and Tessier's facial cleft number 2.
AB  - Choanal atresia is one of the most commonly observed congenital abnormalities of
      the nose. This defect is frequently associated with other congenital anomalies.
      One of the anomalies, which is rarely encountered is a Tessier's facial cleft 2.
      In this report, we present a 6-year-old girl who was brought to our department
      with complaints of nasal obstruction and chronic nasal discharge. On examination,
      a scar was seen on the left ala of her nose due to the former repair of a
      congenital defect. We found hypoplastic nasal cavities and bilateral choanal
      atresia demonstrated by rigid and flexible endoscopy. A CT scan supported these
      findings. This coexistence of bilateral choanal atresia with a number 2 facial
      cleft is an addition to a formerly proposed classification of laterofacial
      clefts. We think that this classification is better for describing the extent and
      origin of these complex lesions.

PMID- 15236898
TI  - Transoral endoscopic resection of a nasopharyngeal hairy polyp.
AB  - Hairy polyps are rare congenital benign tumors that usually present a
      pedunculated mass in the oronasopharynx. A hairy polyp originating from the left
      eustachian tube orifice was found in a 7-month-old girl presenting sleep apnea
      and blood-tinged vomiting. This was successfully removed by transoral surgery
      under endoscopic visualization. The endoscope-guided surgery may help avoid
      undesirable complications as well as completely excise the lesions attached close
      to the eustachian tube openings.

PMID- 15236899
TI  - Recurrent acute otitis media associated meningitis in a patient with a
      contralateral cochlear implant and bilateral cochleovestibular dysplasia.
AB  - OBJECTIVE: To illustrate that a patient with a cochlear implant may be at
      increased risk of meningitis secondary to developmental anatomic abnormality
      associated with the underlying sensorineural hearing loss, as opposed to the
      implant itself. METHODS: Case report. RESULTS: Our 12-year-old patient has
      bilateral cochlear dysplasia, profound sensorineural hearing loss and no prior
      history of recurrent acute otitis media or meningitis. He underwent a left
      cochlear implant at 8 years of age and subsequently experienced three episodes of
      right acute otitis media and meningitis over the next 4 years. Middle ear
      exploration revealed a cerebrospinal fluid leak. A right radical mastoidectomy
      with closure of the external auditory canal, removal of the tympanic membrane,
      malleus, and incus, closure of the Eustachian tube, and obliteration of the
      mastoid and middle ear with abdominal fat has prevented further episodes.
      CONCLUSION: Meningitis in a patient with a cochlear implant is not necessarily
      related to the implant.

PMID- 15236900
TI  - Rosai-Dorfman disease associated with neurosensorial hearing loss in two
      siblings.
AB  - Rosai-Dorfman disease (RDD) is an uncommon pathologic condition of unknown
      ethiology with an idiopathic proliferation of the hystiocytes. It is generally
      presented with massive bilateral hypertrophy of the cervical lymph nodes. But
      other lymph nodes may also be involved. Approximately, 30% of these patients have
      extra nodal mass or lesion with different signs or symptoms depending on
      localization. We present two male siblings with Rosai-Dorfman disease who have
      classical cervical lymphadenopathy associated with progressive neurosensorial
      hearing loss and dural-based intracranial lesions.

PMID- 15236901
TI  - Pistachio nutshell foreign body of the oral cavity in two children.
AB  - Pistachio nutshell foreign bodies have been documented in the literature,
      occurring most commonly in the bronchi. The objective of this study is to report
      on two cases of oral cavity lesions, which were subsequently found to be
      pistachio nutshell foreign bodies. The first patient is a 9-month-old male who
      presented with a hard palate mass measuring 1.5 cm. The patient was evaluated in
      the operating room, and found to have a submucosal pistachio nutshell foreign
      body. The second patient is a 17-month-old female who presented with a firm,
      fixed midline hard palate mass. The lesion was subsequently noted to dislodge
      from the palate, and was identified as a pistachio nutshell.

PMID- 15236902
TI  - Adjusting the endotracheal tube tip in management of tracheomalacia in an infant.
AB  - Tracheomalacia (TM) is an occult central airway problem that may block the
      endotracheal tube (ETT) tip and cause ventilation risk. Traditional physical
      examination, chest radiograph, end-tidal CO2 monitoring and blood gas analysis do
      not easily make the correct diagnosis. Ultra-thin flexible bronchoscopy (FB) is
      convenient and useful to verify this rare type of ETT obstruction and can also
      guide the adjustment of the ETT tip to a correct location. We report two TM
      infants who were successfully diagnosed and managed by FB to correctly reposition
      the ETT tip.

PMID- 15236903
TI  - Complete fistula of the second branchial cleft: case report of catheter-aided
      total excision.
AB  - The authors report an extremely rare case of complete fistula of the second
      branchial cleft, with an external opening in the skin and an internal opening in
      the oropharyngeal mucosa. A 13-year-old girl presented with the complaint of
      intermittent drainage from the right side of her neck, a problem that had existed
      since birth. Fistulography revealed a complete fistula of the second branchial
      cleft. Before surgical excision, a 4-F catheter and a 0.018-in guide-wire were
      inserted into the external opening of the fistula and passed through to the
      tonsillar region under fluoroscopic guidance. The infrahyoid segment and
      parapharyngeal segment of the fistula were then excised through first- and second
      step neck incisions, respectively. In this case, tonsillectomy was not necessary.
      Pathological examination of the wall of the fistula revealed lymphoid tissue
      containing lymphoid follicles. This report describes a technique in which
      complete excision of a fistula of the second branchial arch is facilitated by
      placing a catheter in the tract.

PMID- 15236904
TI  - Hearing evaluation in two sisters with a T8993G point mutation of mitochondrial
      DNA.
AB  - We report on two sisters with a T8993G point mutation of mitochondrial DNA, and
      their hearing evaluation. Considering auditory function, hearing in the elder
      sister remains almost normal. However, in the younger sister, the auditory
      brainstem response (ABR) threshold has fluctuated remarkably during a 3-year
      follow-up. The threshold changes of ABR in the younger sister suggest that her
      hearing problems may well be caused by both cochlear nerves and retrocochlear
      lesions. Our experience is clinically important because there have been only a
      few reports on hearing evaluation in patients with a T8993G point mutation of
      mitochondrial DNA.

PMID- 15236905
TI  - A comparison between SNaPshot, pyrosequencing, and biplex invader SNP genotyping
      methods: accuracy, cost, and throughput.
AB  - Three methods of Single Nucleotide Polymorphism (SNP) detection: SNaPshot,
      Pyrosequencing and Biplex Invader, with two different chemistries were
      investigated to compare, (1) accuracy, (2) ease of use, (3) throughput
      capability, and (4) cost. We genotyped 192 human DNA samples across 24 SNPs
      (minor allele frequencies above 30%), of which seven SNPs were genotyped with all
      three methods. We show that the Biplex Invader genotyping method was found to be
      the most accurate and easiest to use with lowest cost, although Pyrosequencing
      provided similar results at a low cost. With little optimization, the accuracy of
      the SNaPshot method was also comparable to these two methods with a higher cost,
      if only singleplex reactions are used.

PMID- 15236906
TI  - Generation of a polyclonal antibody that simultaneously detects multiple Ser/Thr
      protein kinases.
AB  - In order to obtain a polyclonal antibody that recognizes various protein kinases,
      a peptide corresponding to an amino acid sequence of a highly conserved subdomain
      (subdomain VIB) of the protein kinase family was synthesized and used for
      immunization. When the synthetic peptide, CVVHRDLKPENLLLAS, was coupled to
      keyhole limpet hemocyanin (KLH) and used to immunize rabbits, polyclonal
      antibodies that detected multiple protein kinases on a Western blot were
      generated. One of the antibodies obtained, KI98, detected a variety of purified
      Ser/Thr protein kinases, such as calmodulin-dependent protein kinase II (CaM
      kinase II), calmodulin-dependent protein kinase IV (CaM-kinase IV), cAMP
      dependent protein kinase, protein kinase C, and Erk2. The antibody detected as
      low as 0.2 ng of protein kinases blotted onto a nitrocellulose membrane by dot
      immunobinding assay. When a rat brain extract was analyzed with this antibody,
      various protein kinases were simultaneously detected. The present anti-peptide
      antibody with a broad spectrum of cross-reactivity to multiple protein kinases
      may be a powerful tool for comprehensive analysis focused on protein kinases.

PMID- 15236907
TI  - A novel protocol for the subcellular fractionation of C3A hepatoma cells using
      sucrose density gradient centrifugation.
AB  - In this paper, we describe a method to obtain a relatively pure mitochondrial and
      microsomal fractions by subcellular fractionation of human hepatoma cell line C3A
      using sucrose as the hypoosmotic medium. The cells were subjected to osmotic
      stress with sucrose and homogenized. Osmolarity was then restored to the cells
      and the organelles were separated by density gradient centrifugation. The protein
      profiles were examined by SDS-PAGE and the purity was analysed by marker enzymes
      and Western blotting. Our results indicate a good separation of mitochondrial and
      microsomal fractions from human hepatoma C3A cells.

PMID- 15236908
TI  - Endochitinase activity determination using N-fluorescein-labeled chitin.
AB  - A fluorimetric method for the determination of endochitinolytic activity using N
      fluorescein-labeled chitin (FITC-Chitin) is proposed, and a procedure for FITC
      Chitin preparation with a degree of FITC content of 2.2 mol% (one FITC molecule
      per 45 glucosamine residues) is described. FITC-Chitin is capable to distinguish
      endochitinase and exochitinase (beta-N-acetylglucosaminidase) activities.

PMID- 15236909
TI  - Sample displacement chromatography of Atlantic Salmon (Salmo salar) thrombin.
AB  - A modified method of sample displacement chromatography (SDC) was used to purify
      active salmon thrombin on a heparin-coupled matrix to near homogeneity in
      milligram amounts from 117 ml plasma. This was achieved by combining a low
      pressure multi-column affinity chromatography system with non-homogenous sample
      application in the order of increasing affinity to Heparin Sepharose. The results
      suggest that this modified method could be useful in protein purification. Some
      characteristics of salmon thrombin are presented.

PMID- 15236910
TI  - A protein-protein binding assay using coated microtitre plates: increased
      throughput, reproducibility and speed compared to bead-based assays.
AB  - Protein-protein interactions, and the factors affecting them, are of fundamental
      importance to all biological systems. Surface plasmon resonance (SPR) and
      isothermal titration calorimetry (ITR) are powerful methods for assaying such
      interactions, but are expensive to implement. In contrast, bead-based pull-down
      assays using affinity tags such as glutathione-S-transferase (GST), require no
      specialist equipment. As a result, such assays are the most popular method for
      analysing protein-protein interactions, despite being time-consuming and prone to
      variability. In respect of these problems, we have modified this form of binding
      assay, using glutathione-coated 96-well plates rather than glutathione-Sepharose
      beads to bind the primary bait protein. Quantitation of bound protein utilises
      ELISA for purified proteins and scintillation counting for in vitro translated
      proteins, rather than the SDS-PAGE-based detection methods used in traditional
      bead-based assays. These modifications result in an approximately 10-fold
      increase in the number of samples that can be assayed daily, and allow results to
      be obtained within hours as opposed to days. We validate the modified assay by
      analysing the equilibrium binding of Munc18 and syntaxin, and also demonstrate
      that association and dissociation kinetics may be measured using this approach.
      The method we describe is generally applicable to any protein-protein interaction
      assay based on affinity tags and is amenable to automation, and so should benefit
      a wide range of biochemical research.

PMID- 15236911
TI  - A new method for detecting single nucleotide polymorphism using GFP-display.
AB  - The single nucleotide polymorphism (SNP) of aldehyde dehydrogenase-2 (ALDH2)
      codon 487, GAA (Glu) or AAA (Lys), was examined using green fluorescent protein
      (GFP)-display, an electrophoretic detection method for single amino acid changes.
      Although no shift in migration between the GFP-ALDH (Glu487) and GFP-ALDH
      (Lys487) fusion proteins was observed on SDS/urea gel, the two migrated to
      different positions when tagged with Asp. The SNP analysis was performed with GFP
      ALDH-Asp3, and GFP-ALDH-Asp3 constructed from donors having the codon GAA/GAA,
      GAA/AAA or AAA/AAA was detected as different patterns as expected. GFP-display is
      potentially a unique method in SNP analysis, which does not require any special
      equipment or chemicals.

PMID- 15236912
TI  - Development of a quantitative, high-throughput cell-based enzyme-linked
      immunosorbent assay for detection of colony-stimulating factor-1 receptor
      tyrosine kinase inhibitors.
AB  - Inhibitors of receptor tyrosine kinases are implicated as therapeutic agents for
      the treatment of many human diseases including cancer, inflammation and diabetes.
      Cell-based assays to examine inhibition of receptor tyrosine kinase mediated
      intracellular signaling are often laborious and not amenable to high-throughput
      cell-based screening of compound libraries. Here we describe the development of a
      nonradioactive, sandwich enzyme-linked immunosorbent assay (ELISA) to quantify
      the activation and inhibition of ligand-induced phosphorylation of the colony
      stimulating factor-1 receptor (CSF-1R) in 96-well microtiter plate format. The
      assay involves the capture of the Triton X-100 solubilized human CSF-1R, from
      HEK293E cells overexpressing histidine epitope-tagged CSF-1R (CSF-1R/HEK293E),
      with immobilized CSF-1R antibody and detection of phosphosphorylation of the
      activated receptor with a phosphotyrosine specific antibody. The assay exhibited
      a 5-fold increase in phosphorylated CSF-1R signal from CSF-1R/HEK293E cells
      treated with colony-stimulating factor (CSF-1) relative to treated vector control
      cells. Additionally, using a histidine epitope-specific capture antibody, this
      method can also be adapted to quantify the phosphorylation state of any
      recombinantly expressed, histidine-tagged receptor tyrosine kinase. This method
      is a substantial improvement in throughput and quantitation of CSF-1R
      phosphorylation over conventional immunoblotting techniques.

PMID- 15236913
TI  - The evolution of the concept of 'fever' in the history of medicine: from
      pathological picture per se to clinical epiphenomenon (and vice versa).
AB  - The medical concept of 'fever' has undergone profound changes throughout the
      centuries. Galen of Pergamon considered fever as a systemic disease in itself,
      and it was only between 17th and 18th century that Hermann Boerhaave provided a
      more careful evaluation of the clinical phenomena related to fever. Apart from
      incorrect theories, a major obstacle to the development of a rational study of
      fever has been the lack of appropriate instruments of measurement; in effect, the
      clinical thermometer was not diffusely used in everyday medical practice until
      the mid 19th century. During this same period Ignaz Semmelweiss postulated that
      the pathological-anatomical changes recorded in women who had died because of
      puerperal fever represented a pathological reality clinically suggested by a
      whole cohort of symptoms and signs, among them fever. Even if enormous progress
      has been made in the 20th century with regard to fever, which is currently
      considered a clinical sign of many different diseases, its etiologic assessment
      remains a challenge. In fact, in 1961 the clinical picture of 'Fever of Unknown
      Origin' was officially defined. Since such diagnostic labelling is in effect a
      cover for our inability to discover the real causes of fever, in this case,
      paradoxically, fever goes back to being the whole pathological picture, just as
      it was retained to be many centuries ago.

PMID- 15236914
TI  - The immunostimulating and antimicrobial properties of lithium and
      antidepressants.
AB  - Eicosanoids are products of arachidonic acid (AA), an essential fatty acid. They
      include prostaglandins (PGs), prostacyclin (PGI2), thromboxanes (TXs),
      leukotrienes (LTs) and hydroxy fatty acids. AA is derived enzymatically from
      membrane phospholipids and to a lesser extent the diet. Eicosanoids self-regulate
      every cell, including those synthesizing serotonin, norepinephrine and dopamine
      and those subserving immune function, such as T-cells, B-cells, natural killer
      cells, macrophages, monocytes and dendritic cells. There is objective evidence
      that prostaglandins regulate the physiology of the hypothalamic-pituitary-adrenal
      axis (HPA). Elucidation of the structure and metabolic pathways of eicosanoids
      galvanized researchers into illuminating their role in physiology, pathology and
      pharmacology. Striking contradictions arose: eicosanoids were shown to activate
      and suppress microorganisms, potentiate and suppress immunity and possess pro-
      and anticancer properties. As prostaglandins are the most heavily studied
      eicosanoids in the context of mood and immunity I will focus on them in this
      article. I will present evidence of the immunostimulating and antimicrobial
      properties of lithium and antidepressants and propose that these properties are
      linked to the antiprostaglandin actions of these compounds.

PMID- 15236915
TI  - Evaluation of tuberculosis transmission in Tehran: using RFLP and spoligotyping
      methods.
AB  - OBJECTIVES: To evaluate the DNA polymorphism among Mycobacterium tuberculosis
      (MTB) strains isolated from new smear positive tuberculosis (TB) patients
      residing in Tehran capital city of Iran, during the year 2001. METHODS: IS6110
      restriction fragment length polymorphism (RFLP) and spoligotyping analyses were
      performed on 129 M. tuberculosis strains. Additional patient's information was
      collected for further epidemiological analyses. Patients whose isolates had
      identical RFLP and spoligotyping patterns were considered a cluster. RESULTS: The
      results show that the IS6110 were polymorphic and the strains with 8 or 9 IS6110
      copy number were more frequently defected (42%). Out of 129 available isolates,
      56 (43%) belonged to clusters and 72 (57%) did not. The risk factors like age,
      sex, family history or close contact and intravenous drug abuse were associated
      with clustering. Whereas, unemployment (61%) and poor living conditions (83%)
      contributed to diseases development in both groups. Spoligotyping of M.
      tuberculosis strains resulted in 46 different patterns, out of which 38 patterns
      were unique and reported for the first time. We found one M. tuberculosis strains
      with a pattern characteristic of the Beijing family. CONCLUSION: In the studied
      time period both reactivation (57%) and recent transmission (43%) were
      contributing to annual new TB cases in Tehran.

PMID- 15236916
TI  - Evaluation of Brucellacapt for the diagnosis of human brucellosis.
AB  - OBJECTIVE: To evaluate the role of Brucellacapt in the diagnosis of human
      brucellosis, and the correlation with the evolution of the disease. METHODS:
      Twenty-six patients who were admitted to the General Hospital of Albacete (Spain)
      over a 2-year period and diagnosed with brucellosis were included in the study.
      One hundred and twenty-three serum samples collected at the time of diagnosis and
      at intervals during and after treatment were tested by the Coombs test, the
      standard seroagglutination test (SAT), and Brucellacapt (a new test based on an
      immunocapture-agglutination technique). To study the specificity of Brucellacapt,
      sera from 20 patients with other infectious diseases and 20 sera from healthy
      donors were included in this study. RESULTS: The sensitivity of the Brucellacapt
      at the moment of diagnosis was similar to the Coombs test (96 and 100%,
      respectively), somewhat higher than that of SAT (73%). And the specificity of the
      Brucellacapt (97.5%) was less than SAT and the Coombs test, that was 100%. The
      correlation between the classical serological tests and Brucellacapt, showed that
      titers in Brucellacapt and Coombs test of patients were both similar in a range
      of 1-2 dilutions. The correlation between Brucellacapt and Coombs (r=0.14) and
      between Brucellacapt and SAT (r=0.0) did not reach statistical significance.
      However, the correlation coefficient between Coombs and SAT was r=0.8.
      CONCLUSIONS: Brucellacapt and Coombs tests showed a similar sensitivity and
      specificity in the diagnosis of human brucellosis. In addition, as Coombs test,
      Brucellacapt could help to diagnose patients with long evolution of brucellosis
      that are not detected with SAT.

PMID- 15236917
TI  - Surveillance of the susceptibility of ocular bacterial pathogens to the
      fluoroquinolone gatifloxacin and other antimicrobials in Europe during 2001/2002.
AB  - OBJECTIVES: To determine the identity of European ocular bacterial pathogens and
      their susceptibility to topical antimicrobial agents. METHODS: Bacterial isolates
      derived from clinically significant ocular infections were collected from 10
      European centres. Bacteria were re-identified and susceptibility to gatifloxacin,
      ciprofloxacin, ofloxacin, fusidic acid, gentamicin and chloramphenicol was
      determined using the NCCLS agar incorporation method at a central testing
      laboratory. RESULTS: Five hundred and thirty-two isolates were submitted for
      analysis. The most common pathogen was methicillin-susceptible Staphylococcus
      aureus, followed by Haemophilus influenzae and Streptococcus pneumoniae.
      Gatifloxacin was the most potent antimicrobial agent tested for isolates from
      each European country as measured by pure MIC or percentage resistance (using 95%
      confidence intervals). Only methicillin-resistant S. aureus was in any way
      refractory to the action of gatifloxacin and other fluoroquinolones. CONCLUSIONS:
      Fluoroquinolones offer broad-spectrum coverage for the treatment of ocular
      pathogens. Gatifloxacin ophthalmic solution should be a significant improvement
      on currently available fluoroquinolones mainly due to enhanced activity against
      streptococci and coagulase-negative staphylococci (which accounted for almost one
      third of ocular pathogens).

PMID- 15236918
TI  - Activity of telithromycin against key pathogens associated with community
      acquired respiratory tract infections.
AB  - OBJECTIVES: To investigate the correlation between in vitro susceptibility of
      isolates and clinical outcomes with telithromycin in respiratory tract
      infections. METHODS: The activity of telithromycin was determined by in vitro
      susceptibility testing of key respiratory tract pathogens isolated from patients
      with community-acquired pneumonia, acute exacerbations of chronic bronchitis or
      acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating
      the clinical efficacy of telithromycin. RESULTS: In this pooled analysis,
      telithromycin mode minimum inhibitory concentration (MIC) and MIC90,
      respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626);
      0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l
      for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus
      influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for
      Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus
      (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and
      bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789),
      respectively. CONCLUSIONS: High levels of in vitro susceptibility to
      telithromycin are paralleled by high rates of clinical cure and bacteriologic
      eradication.

PMID- 15236919
TI  - Genomic analysis of penicillin-resistant Streptococcus pneumoniae in Southeastern
      Michigan.
AB  - OBJECTIVE: The emergence of multidrug resistance within Streptococcus pneumoniae
      population was analysed, correlating penicillin resistance Pen(R) with secondary
      antibiotic resistance, capsular serotype, and genetic diversity among isolates.
      METHODS: DNA fingerprinting, following macro-restriction enzyme digestion and
      pulse field gel electrophoresis (PFGE), and restriction fragment analysis of the
      PBP 2b gene, following PCR amplification, were performed on the Pen(R) S.
      pneumoniae, among 377 clinical isolates obtained from the clinical microbiology
      laboratory (University of Michigan Medical Center). RESULTS: Overall 35% of the
      isolates were Pen(R) of which 45% demonstrated high-level penicillin (Pen(R)-R,
      MIC>1). Respiratory isolates were more likely to be Pen(R) (p <0.001) than non
      respiratory isolates and the rate of Pen(R)-R was significantly increased in
      children <10 years of age (59.6%, p <0.02). Secondary antibiotic resistance was
      more frequently associated with Pen(R)-R. Genomic DNA fingerprinting analysis and
      restriction fragment analysis of the PBP 2b gene demonstrated genomic divergence
      with discrete conserved pattern in the PBP 2b gene among the resistant isolates.
      CONCLUSION: The emergence of multidrug resistance in the S. pneumoniae population
      in SE Michigan is not due to expansion of a single or limited number of resistant
      clones, is occurring most frequently in the paediatric population and is
      associated with a decreased susceptibility to penicillin.

PMID- 15236920
TI  - Invasive pulmonary aspergillosis with spontaneous resolution and the diagnostic
      utility of PCR from tissue specimens.
AB  - This case describes a 61-year-old apparently immunocompetent female with invasive
      pulmonary aspergillosis (IPA) and eosinophilia who demonstrated spontaneous
      clinical and radiological recovery. The patient had a history of asthma and had
      been corticosteroid dependent until 2 months prior to her presentation. This
      report explores the role of PCR in confirming the diagnosis of invasive
      aspergillosis in circumstances where only histological data are available and
      highlights the fact that invasive infections with Aspergillus spp. can occur
      without profound immunological deficiency. The case also documents the resolution
      of IPA without specific therapy.

PMID- 15236921
TI  - Could neonatal disseminated herpes simplex virus infections be treated earlier?
AB  - INTRODUCTION: Neonatal disseminated herpes simplex virus (HSV) infection can
      cause rapidly progressive multiple organ failure with an 85% mortality if
      untreated. Early recognition and treatment may improve outcome [N Engl J Med
      324(1991)450]. OBJECTIVES: (i) To determine the number and presentation of
      neonates with disseminated HSV admitted to an intensive care unit. (ii) To
      determine paediatric Specialist Registrar (SpR) awareness of the diagnosis and
      management of a typical potential case of neonatal disseminated HSV. METHODS: (i)
      A 10-year review of case notes of neonates admitted to the intensive care unit
      (ICU) at Great Ormond Street Hospital. (ii) A telephone questionnaire of 'on
      call' Paediatric SpR's in the London area. RESULTS: Eight cases of confirmed
      disseminated HSV infection were identified. All died. Each case followed a
      similar clinical course with presentation between days 5-9 of life (median day
      7). A short prodrome preceded the rapid development of disseminated intravascular
      coagulopathy (DIC), hepatitis and multiple organ failure. Only three cases
      received antiviral treatment in the first 24 h after hospital admission. None of
      the 30 registrars who were interviewed initially considered disseminated HSV in
      the differential diagnosis of a 7-day-old baby presenting with non-specific signs
      of sepsis. Only 4/30 referring unit protocols included disseminated HSV in the
      differential diagnosis of neonatal sepsis. CONCLUSIONS: HSV infection should be
      considered in the differential diagnosis of the acutely unwell neonate. This
      condition is rare but well documented in the literature. Effective antiviral
      therapies exist but are often not started early in the clinical course. Awareness
      of this condition needs to be increased.

PMID- 15236922
TI  - Enterovirus-related type 1 diabetes mellitus and antibodies to glutamic acid
      decarboxylase in Japan.
AB  - OBJECTIVES: In order to clarify the relationship between enteroviruses and type 1
      diabetes mellitus in Japan we investigated enteroviral RNA in serum from children
      with type 1 diabetes mellitus. METHODS: We investigated enteroviral RNA in serum
      from children with type 1 diabetes mellitus by using highly sensitive RT-PCR.
      Additionally the sequences and viral loads were determined and compared with anti
      coxsackie virus antibodies and anti-glutamic acid decarboxylase (GAD) antibodies.
      RESULTS: RT-PCR for enterovirus was positive in 23 (37.7%) from 61 samples. The
      positivity had no disparity of age, but decreased by aging after the occurrence
      of type 1 diabetes mellitus. The sequences of the positives were similar as those
      of coxsackie B4. The viral loads revealed that there was no positive patient with
      high titers of anti-GAD antibodies. CONCLUSION: In Japan there is some
      correlation with type 1 diabetes mellitus and enterovirus. The pathophysiology of
      type 1 diabetes mellitus seems to consist of a direct destruction by persistent
      coxsackie virus and the autoimmune mechanism through autoantibodies against beta
      cells.

PMID- 15236923
TI  - Characteristics and geographical profile of strongyloidiasis in healthcare area
      11 of the Valencian community (Spain).
AB  - INTRODUCTION: This study describes the epidemiological characteristics of all
      cases of strongyloidiasis diagnosed in the period 1995-1999 (both years included)
      in Area 11 of the Valencian Community (Spain) and their possible correlation to
      certain geographical and environmental conditions. MATERIAL AND METHODS: This is
      a retrospective, descriptive study. Information was collected using a telephone
      survey. RESULTS: A total of 473 cases of strongyloidiasis were diagnosed. Of the
      total patients, 282 (60%) answered to the survey. There were 342 males (72%) and
      131 females (28%). Ninety-four percent of the patients were in the 51-91 years
      age interval. Only three patients had been born abroad, while 15 had been on
      brief holidays to countries where the disease is endemic. The largest
      concentration of cases was found in zones 1 (0.49%) and 6 (0.9%), both having
      similar geomorphic characteristics. The professional activity of patients was
      recorded in 215 cases. The most frequent occupation was agriculture, with 124
      cases (58%). Risk activities were recorded in 184 cases, the growing of rice in
      145 patients (79%) being the most important. DISCUSSION: Strongyloides
      stercoralis infestation is endemic and possibly related to agricultural
      activities performed in previous years, and to the geographical characteristics
      of some parts of the area.

PMID- 15236924
TI  - Bronchiolitis obliterans organizing pneumonia as a manifestation of AIDS: case
      report and literature review.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a disease of the small
      airways characterized by intraluminal polyps of myxoid connective tissue.
      Although various infectious and non-infectious agents have been implicated as
      possible precipitants of BOOP, the concomitant occurrence of BOOP with human
      immunodeficiency virus (HIV) infection has rarely been described. We describe a
      unique case in which BOOP was a presenting feature in a patient with newly
      diagnosed AIDS, and we review the literature of BOOP occurring in the setting of
      HIV infection.

PMID- 15236925
TI  - The diagnosis of acute hepatitis C virus infection during seroconversion: an
      important therapeutic opportunity.

PMID- 15236926
TI  - Chalk and cheese: symptomatic hypocalcaemia during paediatric anti-tuberculous
      therapy.
AB  - Standard anti-tuberculosis therapy may disrupt normal vitamin D metabolism and
      consequently calcium homeostasis, but this is previously unreported in paediatric
      patients. We describe two children developed symptomatic hypocalcaemia secondary
      to hypovitaminosis D, which had been precipitated by rifampicin and isoniazid.
      The complex relationship between tuberculosis, anti-tuberculosis therapy, vitamin
      D metabolism and calcium, together with the clinical implications, are discussed.

PMID- 15236927
TI  - Macrophage migration inhibitory factor (MIF) in chinese amphioxus as a molecular
      marker of immune evolution during the transition of invertebrate/vertebrate.
AB  - Macrophage migration inhibitory factor (MIF) is an important cytokine related to
      host defenses and autoimmune diseases. Here, we reported two full-length cDNA
      clones isolated from Chinese amphioxus (Branchiostoma belcheri tsingtaunese).
      Amino acid sequences analysis and structure prediction of these two molecules,
      called Bbt-MIF-I and Bbt-MIF-II, respectively, indicated that several
      conservative domains existed in the two amphioxus MIFs and their sequences were
      highly homologous to their counterparts of other species. Intriguingly, the Bbt
      MIFs gene is present in multi-copy per haploid genome, which is very unusual
      compared with vertebrate's MIF gene given the known genome duplication theory.
      The genomic copy number, expression pattern of MIF gene and phylogenetic analysis
      of MIF proteins all suggested that a leap forward happened for MIF gene during
      the evolution from invertebrate to vertebrate. Considering the crucial role of
      MIF in innate immunity, MIF might serve as one of key molecular markers of
      evolution of immune system.

PMID- 15236928
TI  - A putative double role of a chitinase in a cnidarian: pattern formation and
      immunity.
AB  - Chitinases are enzymes that degrade chitin, the second most abundant polymer in
      nature. They are ubiquitous among living organisms where they play a role in
      development, food-digestion and innate immunity. We have cloned and characterized
      the first cnidarian chitinase cDNA from the hydroid Hydractinia. The Hydractinia
      chitinase exhibits a typical secreted family 18 hydrolases primary structure. In
      situ hybridization and RT-PCR experiments showed that it is exclusively expressed
      in ectodermal tissues of the animal, only following metamorphosis while
      undetectable in embryonic and larval stages. Most prominent expression was
      observed in the stolonal compartment of colonies, structures that are covered by
      a chitinous periderm. Chitinase mRNA was detected in new branching points along
      stolons and in hyperplastic stolons indicating a role of the enzyme in pattern
      formation and allorecognition. It was also expressed in polyps where it was
      mostly restricted to their basal portion. This expression pattern suggests that
      HyChit1 also fulfills a role in host defense, probably against fungal and
      nematode pathogens. Endodermal expression of HyChit1 has never been observed,
      suggesting that the enzyme does not participate in food-digestion.

PMID- 15236929
TI  - Protochordate concordant xenotransplantation settings reveal outbreaks of donor
      cells and divergent life span traits.
AB  - If fulminate rejection in allogeneic and xenogeneic engraftments is not an
      evolutionary relict feature, then any treatment that ablates the host
      surveillance's effector arms capabilities and eliminates graft vs. host
      reactivity should induce donor chimerism in transplant settings. We demonstrate
      here marked proliferative response of Botryllus (Urochordata) blood cells months
      following their infusions (2x10(4)-10(5) blood cells per host) into the
      concordant xenogeneic environment of irradiated Botrylloides soma. The state of
      infused cells was followed by Botryllus specific microsatellite alleles on DNA
      samples from host zooids and vascular system. Increased growth rates and life
      spans of engrafted hosts in some cases, and sudden chimerical death following the
      outbreak of donor cells in others, indicate a 'double-edged sword' expression of
      concurrent evolutionary selected mechanisms. This DES phenomenon in immunity
      underlies divergent stem cell competition phenomena in multicellular organisms,
      leading in mammals, to cases of autoimmune diseases vis-a-vis long-lasting
      microchimerism events following an iatrogenic transplantation.

PMID- 15236931
TI  - Anaphylatoxin-like molecules generated during complement activation induce a
      dramatic enhancement of particle uptake in rainbow trout phagocytes.
AB  - Here we have identified a serum fraction containing approximately 8-kDa molecules
      with an unexpected capacity to greatly enhance particle uptake in trout head
      kidney leukocytes (HKLs). This approximately 8-kDa particle-uptake enhancing
      fraction (PUEF-8) was purified from complement-activated serum by gel filtration
      chromatography. Mass spectrometric analysis and reactivity of anti-trout C3-1 and
      C4 antibodies, indicated the presence of C3a, C4a and C5a molecules in PUEF-8.
      Using a newly developed flow cytometric assay that measures the capacity of cells
      to ingest fluorescent beads, we showed that PUEF-8 induced a striking enhancement
      (344+/-50% higher than the PBS control value) in the number of HKLs ingesting
      three or more beads. In contrast, the effect of PUEF-8 on peripheral blood
      leukocytes (PBLs) was almost negligible. Interestingly, PUEF-8 acted as a strong
      chemoattractant for both HKLs and PBLs. These findings suggest a novel role for
      the anaphylatoxins generated during complement activation in teleost fish.

PMID- 15236932
TI  - Organization and expression of thirteen alternatively spliced exons in catfish
      CD45 homologs.
AB  - CD45, also known as LCA, is a transmembrane protein tyrosine phosphatase encoded
      by the PTPRC gene. In mammals, it plays an important role in T and B cell
      receptor and cytokine signaling by maintaining receptor associated kinases in an
      active state. A prominent CD45 feature is alternative splicing of exons encoding
      the N-terminus, resulting in the generation of several isoforms. The expression
      of isoforms is tightly regulated and dependent on the developmental/activation
      state of the lymphocyte. Nevertheless, the significance of these multiple
      isoforms in mammals is poorly understood. In this study, the channel catfish CD45
      homolog was sequenced and found to be similar to CD45 of other species. However,
      unlike mammalian CD45, it appears that up to 13 exons are used in producing
      multiple alternatively spliced CD45 variants in catfish cells. These 13
      alternatively spliced exons variably encode for O-linked glycosylation sites.
      Several of the exons are identical or very similar, suggesting gene duplication
      of a block of four exons. As demonstrated by RT-PCR, many of the alternatively
      spliced forms of catfish CD45 are differentially expressed in lymphoid cell lines
      with B cells expressing larger isoforms than do T cells. Furthermore,
      immunoprecipitation experiments utilizing anti-catfish CD45 mAbs substantiated
      that different size CD45 isoforms are expressed at the protein level on catfish T
      and B cells.

PMID- 15236933
TI  - Characterization of Atlantic halibut (Hippoglossus hippoglossus) Mx protein
      expression.
AB  - Mx proteins are antiviral GTPases that are induced by type I interferons in
      vertebrates. An Atlantic halibut Mx cDNA (HHMx) was recently cloned. In this
      work, a polyclonal antiserum against HHMx protein was generated that detected a
      71 kDa protein in the nuclei of Chinook salmon embryo cells transfected with the
      HHMx cDNA. Mx protein expression in organs of halibut was studied by immunoblot
      analysis after injection with the double-stranded RNA poly I:C or infectious
      pancreatic necrosis virus. Poly I:C stimulated increased Mx protein expression in
      liver, kidney, heart, spleen, gills and intestine. The Mx protein level in liver
      reached a maximum after 3 days and remained elevated for 14 days after treatment.
      IPNV infection resulted in increased Mx protein in liver from 4 to at least 35
      days. Immunocytochemical detection of Mx proteins in blood smears from poly I:C
      treated halibut indicated that a cytoplasmic Mx form might exist in this species.
      Detection of Mx proteins in blood leukocytes could thus work as an early non
      lethal test for viral infections.

PMID- 15236934
TI  - Potential involvement of rainbow trout thrombocytes in immune functions: a study
      using a panel of monoclonal antibodies and RT-PCR.
AB  - The functional relationship between fish and mammalian thrombocytes is relatively
      unknown. In this study, a panel of monoclonal antibodies (mAbs) was used to
      investigate the functional properties of rainbow trout thrombocytes. The mAbs
      recognize cell-surface molecules on thrombocytes with molecular weights ranging
      from 17 to 160 kDa. Flow cytometric and immuno-electron microscopic analyses
      demonstrate that these molecules are expressed at different levels and that
      surface expression increased upon activation with bovine collagen. Two of these
      cell-surface molecules (17 and 21 kDa) were directly involved in collagen-induced
      aggregation of thrombocytes since aggregation was blocked upon pre-treatment with
      mAbs that recognize the two surface markers. Interestingly, the percentage of
      thrombocytes in blood increased after stimulation using different antigens. The
      transcriptional profile of trout thrombocytes was then examined after immuno
      magnetic enrichment using the described mAbs to assess potential roles of trout
      thrombocytes in immune functions. Trout thrombocytes express components of the
      MHC class Ia pathway, IL1beta, TNFalpha, TGFbeta, the interleukin receptor common
      gamma chain as well as CXC and CC chemokines. MHC class IIB and TNFalpha were
      expressed at low levels in resting thrombocytes. No evidence was found for the
      expression of TCRalphabeta, Ig heavy chain, CD8alpha or CK1 mRNA. Taken together,
      these results suggest that rainbow trout thrombocytes express molecules involved
      in activation, aggregation and genes encoding proteins, that are involved in
      antigen presentation and immune regulation.

PMID- 15236935
TI  - The effect of a translucent post on resin composite depth of cure.
AB  - OBJECTIVE: To evaluate the effect of a light-transmitting post on the depth of
      cure of a resin composite. METHODS: Acetate resin molds were filled with resin
      composite in which a light-transmitting post was inserted into the center and
      photopolymerized to the manufacturer's recommendations. Identical molds without a
      light-transmitting post were photopolymerized in a similar matter and served as a
      control. Molds were sectioned on a water-cooled, diamond saw at prescribed
      distances and the depth of cure was determined using a Knoop Hardness bottom-to
      top ratio criterion. Data within each group were analyzed using 2-way (depth-by
      distance) repeated measure ANOVA. Between-group contrasts (post versus no post)
      were accessed by a 3-way (2 within-subjects and 1 between-subjects) ANOVA with
      critical p = 0.05. RESULTS: The presence of the post did increase (p < 0.001)
      Knoop Hardness values in simulated apical regions as compared to a control.
      However, there was no difference in the depth of cure between the groups (3-way
      analysis p = 0.2) and also when evaluated using an 80% bottom-to-top Knoop
      Hardness ratio. SIGNIFICANCE: The results suggest that these posts may have a
      limited utility when judged against a Knoop Hardness ratio criterion.

PMID- 15236936
TI  - Numerical analysis of tooth mobility: formulation of a non-linear constitutive
      law for the periodontal ligament.
AB  - OBJECTIVE: The aim of the present work is the analysis of mobility of human
      dentition under the action of physiological short-term loading by using a
      numerical approach. The mobility of tooth is mainly attributed to the deformation
      of the periodontal ligament, hence particular attention is focused on the
      definition of a suitable constitutive model for this soft tissue. METHODS: A
      numerical model of human upper incisor and periodontum is proposed by means of
      the finite element method. The mechanical response of the most deformable
      constituent, i.e. the periodontal ligament, is described by using a hyperelastic
      constitutive model. RESULTS: Numerical analyses show an effective correspondence
      with in vivo experimental tests, in literature, on tooth mobility caused by the
      application of intrusive loads. The model proves to offer valid results, leading
      to a general, reliable and efficient numerical approach. SIGNIFICANCE: The
      hyperelastic approach allows the description of the mechanical response of the
      periodontum under short lasting loads, according to the characteristic non-linear
      behavior of the PDL. This approach overcomes the approximation caused by the
      adoption of simplified models, widely reported in literature, and leads to a
      valid definition of tooth movement by means of an effective numerical procedure.

PMID- 15236937
TI  - Optimizing mechanical properties of laser-welded gold alloy through heat
      treatment.
AB  - OBJECTIVE: The goal of this work was to improve the mechanical strength of laser
      welded gold alloy with age-hardenability at intraoral temperature. METHODS: The
      gold alloy was cast conventionally in plate patterns (0.5 mm x 3.0 mm x 20 mm).
      After bench-cooling the mold to room temperature (as-cast state), transverse
      sections of the plate were made at mid-span. They were butted against one another
      and welded using Nd:YAG laser (current: 320 A; time: 10 ms; spot diameter: 1 mm).
      Three laser pulses were applied from both sides to cover the joint width (3.0 mm)
      of the specimens before or after solution heat treatment at 700 degrees C/5 min.
      Uncut control specimens (non-welded) were also prepared. After solution
      treatment, two different heat treatments were given the laser-welded specimens:
      high-temperature aging at 250 degrees C/15 min, or intraoral aging at 37 degrees
      C/3 days. Control specimens underwent all of the heat treatments after solution
      treatment. Tensile testing was conducted at a crosshead speed of 2 mm/min and a
      gauge length of 10 mm. RESULTS: Solution treatment of the gold alloy before laser
      welding did not improve the mechanical strength of laser-welded gold alloy after
      high-temperature aging or intraoral aging. The joint strengths of laser-welded
      gold alloy were improved only by solution heat treatments after laser-welding and
      subsequent aging treatment at high or intraoral temperatures. SIGNIFICANCE: The
      results of this study indicated that laser-welded cast gold alloy prostheses aged
      at high or intraoral temperatures produce high strength when they are solution
      treated after laser-welding.

PMID- 15236938
TI  - Storage effect of a pre-activated silane on the resin to ceramic bond.
AB  - OBJECTIVES: The purpose of this study was to investigate the process of
      hydrolysis and chemical stability of a pre-activated silane solution stored for
      different periods of time. The tensile bond strength of resin composite to
      ceramic was also evaluated in order to determine the functional effectiveness
      after storage of the pre-activated silane solutions. METHODS: Silane solutions
      using gamma-methacryloxypropyltrimethoxysilane (gamma-MPTS), acetic acid and
      ethanol were freshly prepared and kept for 15 min, 2 h, 24 h, 1 week, 1 month, 6
      months, and 1 year. The solutions were analyzed using a 2000 Perkin-Elmer Fourier
      transform infrared (FT-IR) spectrophotometer. For the tensile bond strength test,
      Ni/Cr rods were prepared with ceramic facings polished to 1 microm. Five groups
      of ceramic surfaces (n = 60) were treated with the pre-activated silane solutions
      and bonded using a luting resin. The process used to prepare the surfaces prior
      to bonding consisted of removing unreacted silane by boiling water and then heat
      treatment. Each group was then subdivided into two groups (n = 30) and stored
      under two different storage conditions before subjecting to the tensile bond
      strength test; either (1) dry at room temperature for 24 h or (2) boiling water
      for 24 h. RESULTS: FT-IR analysis showed that nearly complete hydrolysis of gamma
      MPTS has occurred 24 h after mixing, followed more slowly by the formation of
      siloxane (Si-O-Si) oligomers. The bond strength test results showed that there
      was no statistically significant difference in the mean tensile bond strength for
      any of the groups either in dry condition or in boiling water (P > 0.05). The
      mode of failure for all groups was predominantly cohesive failure within the
      resin. The silane bond was also capable of resisting hydrolytic attack in boiling
      water for all the groups. SIGNIFICANCE: From the results of this study it can be
      concluded that, when using an appropriate silane application technique, the
      adhesive effectiveness of a pre-activated silane solution based on gamma-MPTS,
      acetic acid and ethanol will not deteriorate when stored for up to 1 year at room
      temperature.

PMID- 15236939
TI  - Influence of substrate, shape, and thickness on microtensile specimens'
      structural integrity and their measured bond strengths.
AB  - OBJECTIVES: To verify whether substrate, shape, or thickness of microtensile
      specimens have a significant influence on their measured bond strength. METHODS:
      Sixty-four extracted molars provided microtensile specimens, which were prepared
      on enamel and dentin, in different shapes and thicknesses. The teeth were
      randomly divided into 16 groups (n = 4). Groups 1-8 included hourglass-shaped
      specimens. In Groups 1-4 specimens were prepared from enamel and in a thickness
      at the bonding interface of 0.5 mm x 0.5 mm, 1 mm x 1 mm, 1.5 mm x 1.5 mm, and 2
      mm x 2 mm, respectively. In these same thicknesses, hourglasses were trimmed in
      Groups 5-8, but the specimens were prepared from dentin. Groups 9-16 included
      specimens obtained following the non-trimming technique. Groups 9-12 provided
      enamel sticks in the four evaluated thicknesses. In these same thicknesses and
      shape but from dentin were cut the specimens of Groups 13-16. Two specimens from
      each group were viewed using a scanning electron microscope. On the other ones,
      microtensile bond strength was measured and the values were statistically
      analyzed. RESULTS: Substrate, shape, and thickness of the specimens had a
      significant effect on their recorded bond strength (p < 0.05). Higher bond
      strength values were recorded by dentin versus enamel specimens and by sticks
      versus hourglasses. Also, bond strength decreased as specimen thickness
      increased. SEM analysis revealed that the trimmed specimens, especially if from
      enamel, often exhibited lines of fracture in the area of action of the bur.
      SIGNIFICANCE: It seems advisable to avoid the trimming action particularly on
      enamel specimens. If the hourglass shape is preferred, the cross-sectional area
      should not exceed 1 mm x 1 mm.

PMID- 15236930
TI  - Transcriptome analysis of hagfish leukocytes: a framework for understanding the
      immune system of jawless fishes.
AB  - Jawless fishes occupy a critical phylogenetic position in understanding the
      origin of the adaptive immune system. Here, we performed large-scale expressed
      sequence tag analysis of leukocytes isolated from the inshore hagfish Eptatretus
      burgeri. Although we found many immunity-related genes such as those involved in
      lymphocyte or hematopoietic cell signaling and development as well as cytokine
      and cytokine receptor genes, MHC molecules or antigen receptors were not
      identified. We characterized two hagfish cDNAs that closely resembled mammalian
      proteins with essential roles in adaptive immunity, one encoding a GATA3-like
      molecule and another encoding a Bruton's tyrosine kinase (Btk)-like molecule. The
      GATA3-like gene of hagfish was equidistant from GATA3 and GATA2 in jawed
      vertebrates. Similarly, the hagfish Btk-like molecule was not Btk itself, but
      qualified as a pre-duplicated form of Btk and Bmx in jawed vertebrates. In total,
      our work provides circumstantial evidence that adaptive immunity is unique to
      jawed vertebrates.

PMID- 15236940
TI  - CAD/CAM-machining effects on Y-TZP zirconia.
AB  - OBJECTIVES: Computer-Aided-Design/Computer-Aided-Manufacturing (CAD/CAM)
      techniques are gaining importance in fabricating crowns and fixed partial
      dentures (FPDs) made of yttria stabilized tetragonal zirconia polycrystals (Y
      TZP). The specific aims of this study were (1) to test the hypothesis that
      surface flaws and microcracks are induced by the grinding of crowns (2) to
      analyze the material removal and the grinding-induced surface layer as well as to
      estimate the crack size caused by machining Y- TZP under conditions simulating
      the grinding of crowns. METHODS: Y-TZP disks and sectioned cylinders with
      polished separation planes were used for the analysis of the grinding procedure.
      While simulating the inner surface grinding of crowns, feed and cutting depth
      were varied (vw = 100, 75, 50 mm/min; ap = 0.1, 0.06, 0.02 mm). SEM was used for
      the quantitative assessment of the machined surface. RESULTS: While the crack
      length is not significantly influenced by the grinding parameters, the type of
      material removed varied with the cutting depth as well as with the feed. Grinding
      induced surface flaws and microcracks were detected at the internal top surface
      of the crowns. Half-cylinders machined under conditions simulating the inner
      surface grinding of crowns showed crack lengths between 2 and 15 microm.
      SIGNIFICANCE: Sectioned specimens with polished section planes are suitable for
      the analysis of the grinding process using the face and peripheral grinding
      procedure. The inner surface grinding of fixed restorations is the most
      challenging step of CAM of crowns and FPDs. Most important appeared to be the
      diamond tool, especially the number and shape of the active diamond grains.

PMID- 15236941
TI  - Physical and mechanical properties of an experimental dental composite based on a
      new monomer.
AB  - OBJECTIVE: The purpose of this study was to investigate the physical and
      mechanical properties of a dental composite based on BTDMA, a new dimethacrylate
      monomer based on BTDA (3,3',4,4'-benzophenone tetracarboxylic dianhydride), and
      to compare these with the properties of a composite based on commonly used Bis
      GMA monomer. METHODS: Experimental composites were prepared by mixing the silane
      treated filler with the monomers. The prepared pastes were inserted into the test
      molds and heat-cured. Light-cured composites were also prepared using
      camphorquinone and amine as photoinitiator system. Degree of conversion of the
      light-cured and heat-cured composites was measured using FTIR spectroscopy. The
      flexural strength, flexural modulus, diametral tensile strength (DTS), water
      sorption, water contact angle, microhardness and thermal expansion coefficient of
      the prepared composites were measured and compared. Water uptake of the monomers
      was also measured. RESULTS: The results showed that the mechanical properties of
      the new composite are comparable with the properties of the Bis-GMA-based
      composite but its water sorption is higher. BTDMA as a monomer containing
      aromatic rings and carboxylic acid groups in its structure gives a composite with
      good mechanical properties. There is a close relation between the contact angle,
      water sorption of the cured composite and water uptake of their monomers.
      SIGNIFICANCE: Finding new monomers as alternatives for Bis-GMA have been a
      challenge in the field of dental materials and any investigation into the
      properties of new composites would be beneficial in the development of dental
      materials.

PMID- 15236942
TI  - Durability of resin dentin interfaces: effects of surface moisture and adhesive
      solvent component.
AB  - OBJECTIVES: To analyze the effects of different surface moisture on bond strength
      (BS) durability of an ethanol/water based, Single Bond (SB); an acetone-based,
      One-Step (OS); and a water-based, Syntac Single Component (SC) adhesive system to
      dentin. METHODS: Forty-five human third molars had their superficial dentin
      surface exposed flat by abrasion. The adhesives were applied to a delimited area
      of 52 mm(2) on either air-dried (30 s) or rewetted surfaces (2.5 or 4.0 microl)
      followed by resin composite build-ups. After storage in water at 37 degrees C (24
      h), the teeth were sectioned to obtain bonded sticks with a cross-sectional area
      of 0.8 mm(2). The sticks, from each tooth, were divided, stored in water at 37
      degrees C and tested either immediately or after 6 months (6 M) at 0.5 mm/min. BS
      was expressed as an index that considers cohesive failures and estimated values
      of premature debonded specimens. RESULTS: Three-way ANOVA showed statistically
      significant effects for moisture degree, storage time and double interactions (p
      < 0.05). While SB and SC achieved higher BS at 0 and 2.5 microl of water, for OS
      the BS was higher at 4.0 microl of water. Regardless of the moisture degrees,
      reductions in BS were observed after 6 M storage for SB and OS (p < 0.05), but
      not for SC (p > 0.05). No difference in BS between the 24 h and 6 M storage was
      found when the moisture was set at the extreme conditions. Significant reduction
      in BS was observed when the moisture was set at 2.5 microl. SIGNIFICANCE: The
      bond strength of different solvent-based adhesive systems gradually decreases
      over time, regardless of the variable moisture pattern used for the bonding
      procedure.

PMID- 15236943
TI  - Interface effects on mechanical properties of particle-reinforced composites.
AB  - OBJECTIVES: Effective bonding between the filler and matrix components typically
      improves the mechanical properties of polymer composites containing inorganic
      fillers. The aim of this study was to test the hypothesis that composite flexural
      modulus, flexure strength, and toughness are directly proportional to filler
      matrix interfacial shear strength. METHODS: The resin matrix component of the
      experimental composite consisted of a 60:40 blend of BisGMA:TEGDMA. Two levels of
      photoinitiator components were used: 0.15, and 0.5%. Raman spectroscopy was used
      to determine degree of cure, and thermogravimetry (TGA) was used to quantify the
      degree of silane, rubber, or polymer attachment to silica and glass particles.
      Filler-matrix interfacial shear strengths were measured using a microbond test.
      Composites containing glass particles with various surface treatments were
      prepared and the modulus, flexure strength, and fracture toughness of these
      materials obtained using standard methods. Mechanical properties were measured on
      dry and soaked specimens. RESULTS: The interfacial strength was greatest for the
      5% MPS treated silica, and it increased for polymers prepared with 0.5% initiator
      compared with 0.15% initiator concentrations. For the mechanical properties
      measured, the authors found that: (1) the flexural modulus was independent of the
      type of filler surface treatment, though flexural strength and toughness were
      highest for the silanated glass; (2) rubber at the interface, whether bonded to
      the filler and matrix or not, did not improve toughness; (3) less grafting of
      resin to silanated filler particles was observed when the initiator concentration
      decreased. SIGNIFICANCE: These findings suggest that increasing the strength of
      the bond between filler and matrix will not result in improvements in the
      mechanical properties of particulate-reinforced composites in contrast to fiber
      reinforced composites. Also, contraction stresses in the 0.5 vs 0.15% initiator
      concentration composites may be responsible for increases in interfacial shear
      strengths, moduli, and flexural strengths.

PMID- 15236945
TI  - Titanium orthodontic brackets: structure, composition, hardness and ionic
      release.
AB  - OBJECTIVES: The aim of the present study was to investigate the composition,
      morphology, bulk structure and ionic release of two brands of titanium
      orthodontic brackets: Orthos2 (Ormco, USA) and Rematitan (Dentaurum, Germany).
      METHODS: Five specimens of each group were examined with computerized X-ray
      microtomography, to reveal the morphology and structure of brackets, whilst resin
      embedded and metallographically polished specimens were subjected to SEM/EDS
      analysis and Vickers microhardness measurements. Brackets were also maintained in
      0.9% saline for 2 months and the ionic release in the immersion medium was
      determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. The
      results of the hardness and ionic release measurements were statistically
      analyzed with two-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: Orthos2
      brackets consisted of two parts, the base (commercially pure Ti grade II) and the
      wing (Ti-6Al-4V alloy), joined together by laser welding, producing large gaps
      along the base-wing interface. The base was of lower hardness (Hv = 145), than
      the wing (Hv = 392) and incorporated a standard foil base-mesh pad. Rematitan
      brackets consisted of commercially pure Ti grade IV, with a single-piece
      manufacturing pattern of virtually identical hardness (p > 0.05) at the base and
      wings, featuring a laser-etched base-mesh pad. The hardness of the Rematitan
      brackets was significantly lower than the hardness of the Orthos2 wings, but
      double the hardness of the Orthos2 base. Released Ti levels were below the
      threshold level (1 ng/ml) of analysis for both materials, whilst traces of Al (3
      ppm) and V (2 ppm) were found in the immersion media for Ti-6Al-4V alloy.
      SIGNIFICANCE: The structural and hardness differences found may influence the
      torque transfer characteristics from activated archwires to the brackets and the
      crevice corrosion potential at the base-wing interface (Orthos2). The detection
      of Al and V in the immersion medium (Orthos2) may imply a different biological
      response from the two types of Ti brackets.

PMID- 15236944
TI  - Effect of aperture size on irradiance of LED curing units.
AB  - OBJECTIVE: The aim of this study was to evaluate the light output from LED-curing
      units measured according to the current ISO standards. The effect of aperture
      size on irradiance was also evaluated. METHOD: The irradiance of light-curing
      units and the depths of cure of composites exposed to these units were determined
      using the methods outlined in ISO standards, ISO/TS10650 and ISO 4049,
      respectively. The irradiance measured through two different sized apertures was
      also measured. RESULTS: The irradiance measured with an aperture was greater than
      that without an aperture. For each light-curing unit and material, there was a
      linear relationship between the depth of cure and the logarithm of the amount of
      exposure, which is defined as the product of the irradiance and irradiation time.
      The correlation coefficients of these linear relationships, using data obtained
      from the different units was only moderate when the irradiance was measured
      without an aperture. The correlations improved with decreasing aperture size.
      SIGNIFICANCE: Since the irradiance is affected by the angular aperture of the
      light guide and the size of the mold for measuring depth of cure of resin in ISO
      4049 is 4-mm diameter, the irradiance through a 4-mm aperture should be used in
      the determination of the relationship between depth of cure and light exposure.

PMID- 15236946
TI  - Gene-nutrient interactions: importance of folates and retinoids during early
      embryogenesis.
AB  - The role that nutritional factors play in mammalian development has received
      renewed attention over the past two decades, as the scientific literature
      exploded with reports of retinoid compounds disrupting craniofacial development,
      and with other reports that folic acid supplementation in the periconceptional
      period can protect embryos from highly significant malformations. As was often
      the case, the situation became far more complicated, as the interaction between
      nutritional factors with selected genes was recognized. In this review, we
      attempt to summarize a complex clinical and experimental literature of
      nutritional factors, their biological transport mechanisms, and the impact that
      they have during early embryogenesis. Although not exhaustive, our goal was to
      provide an overview of important gene-nutrient interactions and a framework for
      their investigation.

PMID- 15236948
TI  - Transplacental lung carcinogenesis: molecular mechanisms and pathogenesis.
AB  - A wide variety of studies in both animal models and human populations have
      demonstrated age-related differences in the susceptibility of the developing
      organism to environmentally prevalent toxicants. While this differential
      susceptibility has been clearly established, the mechanistic basis for these age
      related differences is still poorly understood. The developing fetus utilizes
      many of the same metabolic and signaling pathways as adult organisms in
      responding to environmental agents. However, it is becoming increasingly evident
      that the fetus is not a "little adult" and exhibits unique biochemical responses
      and gene expression profiles to chemical and physical agents. Because of the
      rapid growth and developmental changes that occur during gestation, the fetus
      represents a particularly challenging research subject as a result of the dynamic
      alterations that occur in gene expression pathways as gene systems are activated
      or repressed during specific stages of development. Thus, an understanding of the
      mechanism(s) that render the developing organism more or less susceptible to
      specific carcinogenic agents is crucial for both regulatory decisions regarding
      the determination of safe levels of toxic chemicals released into the environment
      and also for determining the effects of therapeutic compounds in younger age
      groups and pregnant women. Concentrating on studies from the author's laboratory,
      this review will highlight recent research on the molecular pathogenesis of
      transplacentally induced tumors. While focusing on the lung, other animal models
      and recent human epidemiological studies will also be discussed to contrast
      similarities and differences in the developing and adult organisms in terms of
      responses to toxic chemicals, including metabolism of environmentally prevalent
      toxicants and alterations in gene systems at the molecular level.

PMID- 15236947
TI  - Developmental immunotoxicology of lead.
AB  - The heavy metal, lead, is a known developmental immunotoxicant that has been
      shown to produce immune alterations in humans as well as other species. Unlike
      many compounds that exert adverse immune effects, lead exposure at low to
      moderate levels does not produce widespread loss of immune cells. In contrast,
      changes resulting from lead exposure are subtle at the immune cell population
      level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced
      immunotoxicity is a pronounced shift in the balance in T helper cell function
      toward T helper 2 responses at the expense of T helper 1 functions. This bias
      alters the nature and range of immune responses that can be produced thereby
      influencing host susceptibility to various diseases. Immunotoxic responses to
      lead appear to differ across life stages not only quantitatively with regard to
      dose response, but also qualitatively in terms of the spectrum of immune
      alterations. Experimental studies in several lab animal species suggest the
      latter stages of gestation are a period of considerable sensitivity for lead
      induced immunotoxicity. This review describes the basic characteristics of lead
      induced immunotoxicity emphasizing experimental animal results. It also provides
      a framework for the consideration of toxicant exposure effects across life
      stages. The existence of and probable basis for developmental windows of immune
      hyper-susceptibility are presented. Finally, the potential for lead to serve as a
      perinatal risk factor for childhood asthma as well as other diseases is
      considered.

PMID- 15236949
TI  - In utero effects of chemicals on reproductive tissues in females.
AB  - Chemicals found in the environment as industrial byproducts or pollutants as well
      as those that are prescribed or part of our daily lives can have multiple effects
      on the human body. The manner in which we are exposed, and the levels we are
      exposed to are significant contributing factors. Adults have the bodily defense
      mechanisms in place to combat exposures to adverse toxicants and general
      pollution at a variety of levels. However, developing organisms may not have
      adequate defense mechanisms, and toxicants can have a significant effect on their
      health and development. In this review, we take particular note of the toxicities
      of chemicals on the developing female reproductive system as a result of in utero
      exposure. Environmental and prescribed chemicals such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs), polycyclic
      aromatic hydrocarbons (PAHs), diethylstilbestrol, and genistein, as well as
      others, will be reviewed for their in utero toxicity in the neuroendocrine
      system, the ovary, oviduct, placenta, uterus, vagina, cervix, and mammary gland.

PMID- 15236950
TI  - Cholinergic systems in brain development and disruption by neurotoxicants:
      nicotine, environmental tobacco smoke, organophosphates.
AB  - Acetylcholine and other neurotransmitters play unique trophic roles in brain
      development. Accordingly, drugs and environmental toxicants that promote or
      interfere with neurotransmitter function evoke neurodevelopmental abnormalities
      by disrupting the timing or intensity of neurotrophic actions. The current review
      discusses three exposure scenarios involving acetylcholine systems: nicotine from
      maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS),
      and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three
      have long-term, adverse effects on specific processes involved in brain cell
      replication and differentiation, synaptic development and function, and
      ultimately behavioral performance. Many of these effects can be traced to the
      sequence of cellular events surrounding the trophic role of acetylcholine acting
      on its specific cellular receptors and associated signaling cascades. However,
      for chlorpyrifos, additional noncholinergic mechanisms appear to be critical in
      establishing the period of developmental vulnerability, the sites and type of
      neural damage, and the eventual outcome. New findings indicate that developmental
      neurotoxicity extends to late phases of brain maturation including adolescence.
      Novel in vitro and in vivo exposure models are being developed to uncover
      heretofore unsuspected mechanisms and targets for developmental neurotoxicants.

PMID- 15236951
TI  - Pesticides and children.
AB  - Prevention and control of damage to health, crops, and property by insects,
      fungi, and noxious weeds are the major goals of pesticide applications. As with
      use of any biologically active agent, pesticides have unwanted side-effects. In
      this review, we will examine the thesis that adverse pesticide effects are more
      likely to occur in children who are at special developmental and behavioral risk.
      Children's exposures to pesticides in the rural and urban settings and
      differences in their exposure patterns are discussed. The relative frequency of
      pesticide poisoning in children is examined. In this connection, most reported
      acute pesticide poisonings occur in children younger than age 5. The possible
      epidemiological relationships between parental pesticide use or exposure and the
      risk of adverse reproductive outcomes and childhood cancer are discussed. The
      level of consensus among these studies is examined. Current concerns regarding
      neurobehavioral toxicity and endocrine disruption in juxtaposition to the
      relative paucity of toxicant mechanism-based studies of children are explored.

PMID- 15236952
TI  - Incorporating pharmacokinetic differences between children and adults in
      assessing children's risks to environmental toxicants.
AB  - Children's risks from environmental toxicant exposure can be affected by
      pharmacokinetic factors that affect the internal dose of parent chemical or
      active metabolite. There are numerous physiologic differences between neonates
      and adults that affect pharmacokinetics including size of lipid, and tissue
      compartments, organ blood flows, protein binding capacity, and immature function
      of renal and hepatic systems. These factors combine to decrease the clearance of
      many therapeutic drugs, which can also be expected to occur with environmental
      toxicants in neonates. The net effect may be greater or lesser internal dose of
      active toxicant depending upon how the agent is distributed, metabolized, and
      eliminated. Child/adult pharmacokinetic differences decrease with increasing
      postnatal age, but these factors should still be considered in any children's age
      group, birth through adolescence, for which there is toxicant exposure.
      Physiologically based pharmacokinetic (PBPK) models can simulate the absorption,
      distribution, metabolism, and excretion of xenobiotics in both children and
      adults, allowing for a direct comparison of internal dose and risk across age
      groups. This review provides special focus on the development of hepatic
      cytochrome P-450 enzymes (CYPs) in early life and how this information, along
      with many factors unique to children, can be applied to PBPK models for this
      receptor population. This review describes a case study involving the development
      of neonatal PBPK models for the CYP1A2 substrates caffeine and theophylline.
      These models were calibrated with pharmacokinetic data in neonates and used to
      help understand key metabolic differences between neonates and adults across
      these two drugs.

PMID- 15236953
TI  - Environmental chemicals in human milk: a review of levels, infant exposures and
      health, and guidance for future research.
AB  - The aim of this review is to introduce the reader to various science and policy
      aspects of the topic of environmental chemicals in human milk. Although
      information on environmental chemicals in human milk has been available since the
      1950s, it is only relatively recently that public awareness of the issue has
      grown. This review on environmental chemicals in human milk provides a resource
      summarizing what is currently known about levels and trends of environmental
      chemicals in human milk, potential infant exposures, and benefits of breast
      feeding relative to the risks of exposures to environmental chemicals. The term
      "environmental chemicals," as it pertains to human milk, refers to many classes
      of exogenous chemicals that may be detected in human milk. For example,
      pharmaceutical agents and alcohol are environmental chemicals that have been
      found in human milk. Other chemicals, such as heavy metals and volatile organic
      compounds, have also been detected in human milk. Most research on environmental
      chemicals in human milk has concentrated on persistent, bioaccumulative, and
      toxic (PBT) chemicals. In this review, a description of human milk is provided,
      including a brief review of endogenous substances in human milk. Determinants of
      levels of PBTs are discussed, as are models that have been developed to predict
      levels of PBTs in human milk and associated body burdens in breast-feeding
      infants. Methodologies for human milk sampling and analysis, and concepts for
      consideration in interpretation and communication of study results, as developed
      by the Technical Workshop on Human Milk Surveillance and Research for
      Environmental Chemicals in the United States are described. Studies which have
      compared the health risks and benefits associated with breast-feeding and formula
      feeding are discussed.

PMID- 15236954
TI  - Mercury exposure in children: a review.
AB  - Exposure to toxic mercury (Hg) is a growing health hazard throughout the world
      today. Recent studies show that mercury exposure may occur in the environment,
      and increasingly in occupational and domestic settings. Children are particularly
      vulnerable to Hg intoxication, which may lead to impairment of the developing
      central nervous system, as well as pulmonary and nephrotic damage. Several
      sources of toxic Hg exposure in children have been reported in biomedical
      literature: (1) methylmercury, the most widespread source of Hg exposure, is most
      commonly the result of consumption of contaminated foods, primarily fish; (2)
      ethylmercury, which has been the subject of recent scientific inquiry in relation
      to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg
      vapor exposure through accidents and occupational and ritualistic practices; (4)
      inorganic Hg through the use of topical Hg-based skin creams and in infant
      teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors,
      and Hg2+ in tissues. This review examines recent epidemiological studies of
      methylmercury exposure in children. Reports of elemental Hg vapor exposure in
      children through accidents and occupational practices, and the more recent
      observations of the increasing use of elemental Hg for magico-religious purposes
      in urban communities are also discussed. Studies of inorganic Hg exposure from
      the widespread use of topical beauty creams and teething powders, and
      fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed.
      Considerable attention was given in this review to pediatric methylmercury
      exposure and neurodevelopment because it is the most thoroughly investigated Hg
      species. Each source of Hg exposure is reviewed in relation to specific pediatric
      health effects, particularly subtle neurodevelopmental disorders.

PMID- 15236955
TI  - The developmental toxicity of perfluoroalkyl acids and their derivatives.
AB  - Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA) have applications in numerous industrial and
      consumer products. Although the toxicology of some of these compounds has been
      investigated in the past, the widespread prevalence of PFOS and PFOA in humans,
      as demonstrated in recent bio-monitoring studies, has drawn considerable interest
      from the public and regulatory agencies as well as renewed efforts to better
      understand the hazards that may be inherent in these compounds. This review
      provides a brief overview of the perfluoroalkyl chemicals and a summary of the
      available information on the developmental toxicity of the eight-carbon
      compounds, PFOS and PFOA. Although the teratological potentials of some of these
      chemicals had been studied in the past and the findings were generally
      unremarkable, results from recent postnatal studies on developmental and
      reproductive indices have prompted consideration of their relevance to human
      health risk. Based on current understanding of the developmental effects of PFOS
      and PFOA in rodents, several avenues of research are suggested that would further
      support the risk assessment of these perfluorinated organic chemicals.

PMID- 15236956
TI  - GTP hydrolysis mechanism of Ras-like GTPases.
AB  - The Ras-like GTPases regulate diverse cellular functions via the chemical cycle
      of binding and hydrolyzing GTP molecules. They alternate between GTP- and GDP
      bound conformations. The GTP-bound conformation is biologically active and
      promotes a cellular function, such as signal transduction, cytoskeleton
      organization, protein synthesis/translocation, or a membrane budding/fusion
      event. GTP hydrolysis turns off the GTPase switch by converting it to the
      inactive GDP-bound conformation. The fundamental GTP hydrolysis mechanism by
      these GTPases has generated considerable interest over the last two decades but
      remained to be firmly established. This review provides an update on the
      catalytic mechanism with discussions on recent developments from kinetic,
      structural, and model studies in the context of the various GTP hydrolysis models
      proposed over the years.

PMID- 15236957
TI  - DNA disentangling by type-2 topoisomerases.
AB  - A type-2 topoisomerase cleaves a DNA strand, passes another through the break,
      and then rejoins the severed ends. Because it appears that this action is as
      likely to increase as to decrease entanglements, the question is: how are
      entanglements removed? We argue that type-2 topoisomerases have evolved to act at
      "hooked" juxtapositions of strands (where the strands are curved toward each
      other). This type of juxtaposition is a natural consequence of entangled long
      strands. Our model accounts for the observed preference for unlinking and
      unknotting of short DNA plasmids by type-2 topoisomerases and well explains
      experimental observations.

PMID- 15236958
TI  - Crystal structures of the ADP and ATP bound forms of the Bacillus anti-sigma
      factor SpoIIAB in complex with the anti-anti-sigma SpoIIAA.
AB  - Cell type-specific transcription during Bacillus sporulation is established by
      sigma(F), the activity of which is controlled by a regulatory circuit involving
      the anti-sigma factor and serine kinase SpoIIAB, and the anti-anti-sigma SpoIIAA.
      When ATP is present in the nucleotide-binding site of SpoIIAB, SpoIIAA is
      phosphorylated, followed by dissociation. The nucleotide-binding site of SpoIIAB
      is left bound to ADP. SpoIIAB(ADP) can bind an unphosphorylated molecule of
      SpoIIAA as a stable binding partner. Thus, in this circuit, SpoIIAA plays a dual
      role as a substrate of the SpoIIAB kinase activity, as well as a tight binding
      inhibitor. Crystal structures of both the pre-phosphorylation complex and the
      inhibitory complex, SpoIIAB(ATP) and SpoIIAB(ADP) bound to SpoIIAA, respectively,
      have been determined. The structural differences between the two forms are subtle
      and confined to interactions with the phosphoryl groups of the nucleotides. The
      structures reveal details of the SpoIIAA:SpoIIAB interactions and how
      phosphorylated SpoIIAA dissociates from SpoIIAB(ADP). Finally, the results
      confirm and expand upon the docking model for SpoIIAA function as an anti-anti
      sigma in releasing sigma(F) from SpoIIAB.

PMID- 15236959
TI  - Periodic transcriptional organization of the E.coli genome.
AB  - The organization of transcription within the prokaryotic nucleoid may be expected
      to both depend on and determine the structure of the chromosome. Indeed,
      immunofluorescence localization of transcriptional regulators has revealed foci
      in actively transcribing Escherichia coli cells. Furthermore, structural and
      biochemical approaches suggest that there are approximately 50 independent loop
      domains per genome. Here I show that in four E.coli strains, genes that are
      controlled by a sequence-specific transcriptional regulator tend to locate next
      to the gene encoding this regulator, or at regular distances that are multiples
      of 1/50th of the chromosome length. This periodicity is consistent with a
      solenoidal epi-organization of the chromosome, which would gather into foci the
      interacting partners; the regulator molecules and their DNA binding sites.
      Binding at genuine regulatory sites on DNA would thus be optimized by co
      transcriptionally translating regulators in their vicinity.

PMID- 15236960
TI  - Studies of the RNA degradosome-organizing domain of the Escherichia coli
      ribonuclease RNase E.
AB  - The hydrolytic endoribonuclease RNase E, which is widely distributed in bacteria
      and plants, plays key roles in mRNA degradation and RNA processing in Escherichia
      coli. The enzymatic activity of RNase E is contained within the conserved amino
      terminal half of the 118 kDa protein, and the carboxy-terminal half organizes the
      RNA degradosome, a multi-enzyme complex that degrades mRNA co-operatively and
      processes ribosomal and other RNA. The study described herein demonstrates that
      the carboxy-terminal domain of RNase E has little structure under native
      conditions and is unlikely to be extensively folded within the degradosome.
      However, three isolated segments of 10-40 residues, and a larger fourth segment
      of 80 residues, are predicted to be regions of increased structural propensity.
      The larger of these segments appears to be a protein-RNA interaction site while
      the other segments possibly correspond to sites of self-recognition and
      interaction with the other degradosome proteins. The carboxy-terminal domain of
      RNase E may thus act as a flexible tether of the degradosome components. The
      implications of these and other observations for the organization of the RNA
      degradosome are discussed.

PMID- 15236961
TI  - The Schizosaccharomyces pombe open promoter bubble: mammalian-like arrangement
      and properties.
AB  - The fission yeast Schizosaccharomyces pombe is often used as a genetic system to
      model processes that apply to higher cells. Here S.pombe was used to study
      promoter DNA opening and transcription initiation by RNA polymerase II. The
      melted region within the adh promoter is about 20 bp in size and has the start
      site near its center. This arrangement is similar to that at the AdML promoter
      but different from that in Saccharomyces cerevisiae. Although expression of human
      TFIIB shifts the start site to the nearby human position, it does not change the
      location of the bubble. The start site shift is directed by the C terminus of
      human TFIIB, in contrast to expectations from S.cerevisiae. The creation of the
      bubble requires the ATPase motifs of XPB. Overall, the data show that promoter
      melting and initiation in fission yeast is much more similar to humans than to
      budding yeast.

PMID- 15236962
TI  - Clustering of protein domains in the human genome.
AB  - We present a systematic study of the clustering of genes within the human genome
      based on homology inferred from both sequence and structural similarity. The 3D
      Genomics automated proteome annotation pipeline () was utilised to infer homology
      for each protein domain in the genome, for the 26 superfamilies most highly
      represented in the Structural Classification Of Proteins (SCOP) database. This
      approach enabled us to identify homologues that could not be detected by sequence
      based methods alone. For each superfamily, we investigated the distribution, both
      within and among chromosomes, of genes encoding at least one domain within the
      superfamily. The results indicate a diversity of clustering behaviours: some
      superfamilies showed no evidence of any clustering, and others displayed
      significant clustering either within or among chromosomes, or both. Removal of
      tandem repeats reduced the levels of clustering observed, but some superfamilies
      still displayed highly significant clustering. Thus, our study suggests that
      either the process of gene duplication, or the evolution of the resulting
      clusters, differs between structural superfamilies.

PMID- 15236963
TI  - Identification of the protein acetyltransferase (Pat) enzyme that acetylates
      acetyl-CoA synthetase in Salmonella enterica.
AB  - Post-translational modification of proteins is an efficient way cells use to
      control the activity of structural proteins, gene expression regulatory proteins,
      and enzymes. In eukaryotes, the Sir2-dependent system of protein
      acetylation/deacetylation controls a number of processes that affect cell
      longevity. Sir2 proteins have NAD(+)-dependent protein deacetylase activity and
      are found in all forms of life. Although the identity of the acetyltransferases
      that partner with Sir2 enzymes is known in eukaryotes, the identity of the
      prokaryotic acetyltransferases is not. We report the identification of the gene
      of Salmonella enterica serovar Typhimurium LT2 encoding the major protein
      acetyltransferase (Pat) enzyme that, in concert with the CobB sirtuin of this
      bacterium, regulates the activity of the central metabolic enzyme acetyl-coenzyme
      A synthetase (Acs). The Pat enzyme uses acetyl-CoA as substrate to modify residue
      Lys609 of Acs. The Pat/CobB system of S.enterica should serve as the paradigm to
      further investigate the contributions of this system to the physiology of
      prokaryotes.

PMID- 15236964
TI  - A HOXA10 estrogen response element (ERE) is differentially regulated by 17 beta
      estradiol and diethylstilbestrol (DES).
AB  - The molecular mechanisms by which estrogens regulate developmental gene
      expression are poorly understood. While 17 beta-estradiol is normally present at
      high concentrations in pregnancy, exposure to the estrogen diethylstilbestrol
      (DES) in utero induces developmental anomalies of the female reproductive tract.
      HOX gene expression is altered by DES, leading to abnormal Mullerian duct
      differentiation. The mechanism of ligand-specific regulation of HOX gene
      expression by estrogens has not been characterized. To elucidate the molecular
      mechanism underlying ligand-specific estrogen regulation of HOXA10 expression, we
      characterized regulatory regions of the human HOXA10 gene. We identified an
      estrogen response element (ERE) in the human HOXA10 gene that mediated
      differential ligand-specific estrogen-responsive transcriptional activation.
      Deletional analysis and reporter expression assays identified two EREs, ERE1 and
      ERE2, each of which drove estrogen-responsive reporter expression in the Ishikawa
      human uterine endometrial adenocarcinoma cell line. ERE1 drove reporter
      expression maximally. This ERE bound ERalpha and ERbeta, and formed a complex
      that included SRC-1, but not CBP, N-CoR or SMRT. HOXA10 ERE1 drove luciferase
      reporter activity to eightfold the level driven by the consensus ERE in response
      to estradiol in Ishikawa cells. While most EREs demonstrate similar
      transcriptional activity in response to DES or estradiol, here estradiol induced
      four- to sevenfold greater reporter activity than did DES from HOXA10 ERE1. DES
      did not alter ER or SRC-1 binding to HOXA10 ERE1. HOXA10 ERE1 therefore
      demonstrated ligand specificity distinct from the consensus ERE, and unrelated to
      changes in ER or coactivator/corepressor binding. The ligand specificity of the
      HOXA10 ERE may explain the molecular mechanism by which DES leads to reproductive
      anomalies; differential ligand-specific activation of HOX genes may be a
      molecular mechanism by which DES signaling leads to inappropriate HOX expression
      and to developmental patterning distinct from that induced by estradiol.

PMID- 15236965
TI  - Coenzyme site-directed mutants of photosynthetic A4-GAPDH show selectively
      reduced NADPH-dependent catalysis, similar to regulatory AB-GAPDH inhibited by
      oxidized thioredoxin.
AB  - Chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of higher plants
      uses both NADP(H) and NAD(H) as coenzyme and consists of one (GapA) or two types
      of subunits (GapA, GapB). AB-GAPDH is regulated in vivo through the action of
      thioredoxin and metabolites, showing higher kinetic preference for NADPH in the
      light than in darkness due to a specific effect on kcat(NADPH). Previous
      crystallographic studies on spinach chloroplast A4-GAPDH complexed with NADP or
      NAD showed that residues Thr33 and Ser188 are involved in NADP over NAD
      selectivity by interacting with the 2'-phosphate group of NADP. This suggested a
      possible involvement of these residues in the regulatory mechanism. Mutants of
      recombinant spinach GapA (A4-GAPDH) with Thr33 or Ser188 replaced by Ala (T33A,
      S188A and double mutant T33A/S188A) were produced, expressed in Escherichia coli,
      and compared to wild-type recombinant A4-GAPDH, in terms of crystal structures
      and kinetic properties. Affinity for NADPH was decreased significantly in all
      mutants, and kcat(NADPH) was lowered in mutants carrying the substitution of
      Ser188. NADH-dependent activity was unaffected. The decrease of kcat/Km of the
      NADPH-dependent reaction in Ser188 mutants resembles the behaviour of AB-GAPDH
      inhibited by oxidized thioredoxin, as confirmed by steady-state kinetic analysis
      of native enzyme. A significant expansion of size of the A4-tetramer was observed
      in the S188A mutant compared to wild-type A4. We conclude that in the absence of
      interactions between Ser188 and the 2'-phosphate group of NADP, the enzyme
      structure relaxes to a less compact conformation, which negatively affects the
      complex catalytic cycle of GADPH. A model based on this concept might be
      developed to explain the in vivo light-regulation of the GAPDH.

PMID- 15236966
TI  - A detailed thermodynamic analysis of ras/effector complex interfaces.
AB  - Many cellular functions are based on the interaction and crosstalk of various
      signaling proteins. Among these, members of the Ras family of small GTP-binding
      proteins are important for communicating signals into different pathways. In
      order to answer the question of how binding affinity and specificity is achieved,
      we analyzed binding energetics on the molecular level, with reference to the
      available structural data. The interaction of two members of the Ras subfamily
      with two different effector proteins, namely Raf and RalGDS, were investigated
      using isothermal titration calorimetry and a fluorescence-based method.
      Experiments with alanine mutants, located in the complex interfaces, yielded an
      energy map for the contact areas of the Ras/effector complexes, which could be
      differentiated into enthalpy and entropy contributions. In addition, by using
      double mutant cycle analysis, we probed the energetic contribution of selected
      pairs of amino acid residues. The resulting energy landscapes of the Ras/effector
      interface areas show a highly different topology when comparing the two
      effectors, Raf and RalGDS, demonstrating the specificity of the respective
      interactions. Particularly, we observe a high degree of compensating effects
      between enthalpy and entropy; differences between these components are much
      greater than the overall free energy differences. This is observed also when
      using the software FOLD-X to predict the effect of point mutations on the crystal
      structures of the different complexes. Prediction of the free energy changes
      shows a very good correlation with the experimentally observed energies.
      Furthermore, in line with experimental data, energy decomposition indicates that
      many different components of large magnitude counteract each other to produce a
      smaller change in overall free energy, illustrating the importance of long-range
      electrostatic forces in complex formation.

PMID- 15236967
TI  - 25 Angstrom resolution structure of a cytoplasmic dynein motor reveals a seven
      member planar ring.
AB  - Dyneins form one of the three major families of cytoskeleton-based motor proteins
      that together drive most of the visible forms of cell and organelle movement. We
      present here a 3D reconstruction of a cytoplasmic dynein motor domain obtained by
      electron microscopy, at 25 Angstrom resolution. This work demonstrates a basic
      motor architecture of a flat, slightly elliptical ring composed of seven
      densities arranged around a partially enclosed central cavity. We have used
      specific Fab tags to localize the microtubule-binding domain; the connecting
      stalk emerges at one end of the motor's long axis. Through proposed fitting of
      representative AAA domain structures, we show that the nucleotide catalytic P-1
      domain is likely located at the opposite end of the motor. Thus mechanisms that
      couple nucleotide hydrolysis with microtubule binding must be propagated around a
      ring structure, in a manner clearly distinct from kinesin or myosin-mediated
      movements. Analysis of the Fab tagged datasets reveals classes of particles with
      stalks protruding at distinct angles from the motor. There is a approximately 40
      degrees variation in microtubule-binding stalk angle that may reflect linkage to
      dynein's mechanochemical cycle. Overall, the work provides sufficient resolution
      to begin the mapping of landmark features onto a dynein motor, and provides a
      foundation for understanding the mechanics of dynein movement.

PMID- 15236968
TI  - High-affinity human antibodies from phage-displayed synthetic Fab libraries with
      a single framework scaffold.
AB  - Phage-displayed synthetic antibody libraries were built on a single human
      framework by introducing synthetic diversity at solvent-exposed positions within
      the heavy chain complementarity-determining regions (CDRs). The design strategy
      of mimicking natural diversity using tailored codons had been validated
      previously with scFv libraries, which produced antibodies that bound to antigen,
      murine vascular endothelial growth factor (mVEGF), with affinities in the 100nM
      range. To improve library performance, we constructed monovalent and bivalent
      antigen-binding fragment (Fab) libraries, and explored different CDR-H3
      diversities by varying the amino acid composition and CDR length. A Fab with sub
      nanomolar affinity for mVEGF was obtained from a library with CDR-H3 diversity
      designed to contain all 20 naturally occurring amino acids. We then expanded the
      library by increasing the variability of CDR-H3 length and using tailored codons
      that mimicked the amino acid composition of natural CDR-H3 sequences. The library
      was tested against a panel of 13 protein antigens and high-affinity Fabs were
      obtained for most antigens. Furthermore, the heavy chain of an anti-mVEGF clone
      was recombined with a library of light chain CDRs, and the affinity was improved
      from low nanomolar to low picomolar. The results demonstrated that high-affinity
      human antibodies can be generated from libraries with completely synthetic CDRs
      displayed on a single scaffold.

PMID- 15236969
TI  - Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis
      EthR implicated in ethionamide resistance.
AB  - Ethionamide has been used for more than 30 years as a second-line
      chemotherapeutic to treat tuberculosis patients who have developed resistance to
      first-line drugs, such as isoniazid (INH) and rifampicin. Activation of the pro
      drug ethionamide is regulated by the Baeyer-Villiger monooxygenase EthA and the
      TetR/CamR family repressor EthR, whose open reading frames are separated by 75 bp
      on the Mycobacterium tuberculosis genome. EthR has been shown to repress
      transcription of the activator gene ethA by binding to this intergenic region,
      thus contributing to ethionamide resistance. We have determined the crystal
      structure of EthR, to 1.7A resolution, revealing a dimeric two-domain molecule
      with an overall architecture typical for TetR/CamR repressor proteins. A 20A long
      hydrophobic tunnel-like cavity in the "drug-binding" domain of EthR is occupied
      by two 1,4-dioxane molecules, a component of the crystallisation buffer.
      Comparing the present structure to those of the homologues Staphylococcus aureus
      QacR and Escherichia coli TetR leads to the hypothesis that the hydrophobic
      cavity constitutes a binding site for an as yet unknown ligand that might
      regulate DNA-binding of EthR.

PMID- 15236970
TI  - Crystal structure of the motor domain of the human kinetochore protein CENP-E.
AB  - The human kinetochore is a highly complex macromolecular structure that connects
      chromosomes to spindle microtubules (MTs) in order to facilitate accurate
      chromosome segregation. Centromere-associated protein E (CENP-E), a member of the
      kinesin superfamily, is an essential component of the kinetochore, since it is
      required to stabilize the attachment of chromosomes to spindle MTs, to develop
      tension across aligned chromosomes, to stabilize spindle poles and to satisfy the
      mitotic checkpoint. Here we report the 2.5A resolution crystal structure of the
      motor domain and linker region of human CENP-E with MgADP bound in the active
      site. This structure displays subtle but important differences compared to the
      structures of human Eg5 and conventional kinesin. Our structure reveals that the
      CENP-E linker region is in a "docked" position identical to that in the human
      plus-end directed conventional kinesin. CENP-E has many advantages as a potential
      anti-mitotic drug target and this crystal structure of human CENP-E will provide
      a starting point for high throughput virtual screening of potential inhibitors.

PMID- 15236971
TI  - Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals
      a novel zinc-binding domain distinct from a RING.
AB  - The really interesting new gene (RING) family of proteins contains over 400
      members with diverse physiological functions. A subset of these domains is found
      in the context of the RING-IBR-RING/TRIAD motifs which function as E3 ubiquitin
      ligases. Our sequence analysis of the C-terminal RING (RING2) from this motif
      show that several metal ligating and hydrophobic residues critical for the
      formation of a classical RING cross-brace structure are not present. Thus, we
      determined the structure of the RING2 from the RING-IBR-RING motif of HHARI and
      showed that RING2 has a completely distinct topology from classical RINGs.
      Notably, RING2 binds only one zinc atom per monomer rather than two and uses a
      different hydrophobic network to that of classical RINGs. Additionally, this
      RING2 topology is novel, bearing slight resemblance to zinc-ribbon motifs around
      the zinc site and is different from the topologies of the zinc binding sites
      found in RING and PHDs. We demonstrate that RING2 acts as an E3 ligase in vitro
      and using mutational analysis deduce the structural features required for this
      activity. Further, mutations in the RING-IBR-RING of Parkin cause a rare form of
      Parkinsonism and these studies provide an explanation for those mutations that
      occur in its RING2. From a comparison of the RING2 structure with those reported
      for RINGs, we infer sequence determinants that allow discrimination between RING2
      and RING domains at the sequence analysis level.

PMID- 15236972
TI  - Structural characterization of unfolded states of apomyoglobin using residual
      dipolar couplings.
AB  - The conformational propensities of unfolded states of apomyoglobin have been
      investigated by measurement of residual dipolar couplings between (15)N and (1)H
      in backbone amide groups. Weak alignment of apomyoglobin in acid and urea
      unfolded states was induced with both stretched and compressed polyacrylamide
      gels. In 8 M urea solution at pH 2.3, conditions under which apomyoglobin
      contains no detectable secondary or tertiary structure, significant residual
      dipolar couplings of uniform sign were observed for all residues. At pH 2.3 in
      the absence of urea, a change in the magnitude and/or sign of the residual
      dipolar couplings occurs in local regions of the polypeptide where there is a
      high propensity for helical secondary structure. These results are interpreted on
      the basis of the statistical properties of the unfolded polypeptide chain, viewed
      as a polymer of statistical segments. For a folded protein, the magnitude and
      sign of the residual dipolar couplings depend on the orientation of each bond
      vector relative to the alignment tensor of the entire molecule, which reorients
      as a single entity. For unfolded proteins, there is no global alignment tensor;
      instead, residual dipolar couplings are attributed to alignment of the
      statistical segments or of transient elements of secondary structure. For
      apomyoglobin in 8 M urea, the backbone is highly extended, with phi and psi
      dihedral angles favoring the beta or P(II) regions. Each statistical segment has
      a highly anisotropic shape, with the N-H bond vectors approximately perpendicular
      to the long axis, and becomes weakly aligned in the anisotropic environment of
      the strained acrylamide gels. Local regions of enhanced flexibility or chain
      compaction are characterized by a decrease in the magnitude of the residual
      dipolar couplings. The formation of a small population of helical structure in
      the acid-denatured state of apomyoglobin leads to a change in sign of the
      residual dipolar couplings in local regions of the polypeptide; the population of
      helix estimated from the residual dipolar couplings is in excellent agreement
      with that determined from chemical shifts. The alignment model described here for
      apomyoglobin can also explain the pattern of residual dipolar couplings reported
      previously for denatured states of staphylococcal nuclease and other proteins. In
      conjunction with other NMR experiments, residual dipolar couplings can provide
      valuable insights into the dynamic conformational propensities of unfolded and
      partly folded states of proteins and thereby help to chart the upper reaches of
      the folding landscape.

PMID- 15236973
TI  - Controlled unfolding and refolding of a single sodium-proton antiporter using
      atomic force microscopy.
AB  - Single-molecule force-spectroscopy was employed to unfold and refold single
      sodium-proton antiporters (NhaA) of Escherichia coli from membrane patches.
      Although transmembrane alpha-helices and extracellular polypeptide loops
      exhibited sufficient stability to individually establish potential barriers
      against unfolding, two helices predominantly unfolded pairwise, thereby acting as
      one structural unit. Many of the potential barriers were detected unfolding NhaA
      either from the C-terminal or the N-terminal end. It was found that some
      molecular interactions stabilizing secondary structural elements were
      directional, while others were not. Additionally, some interactions appeared to
      occur between the secondary structural elements. After unfolding ten of the 12
      helices, the extracted polypeptide was allowed to refold back into the membrane.
      After five seconds, the refolded polypeptide established all secondary structure
      elements of the native protein. One helical pair showed a characteristic spring
      like "snap in" into its folded conformation, while the refolding process of other
      helices was not detected in particular. Additionally, individual helices required
      characteristic periods of time to fold. Correlating these results with the
      primary structure of NhaA allowed us to obtain the first insights into how
      potential barriers establish and determine the folding kinetics of the secondary
      structure elements.

PMID- 15236974
TI  - A highly amyloidogenic region of hen lysozyme.
AB  - Amyloid fibrils obtained after incubating hen egg-white lysozyme (HEWL) at pH 2.0
      and 65 degrees C for extended periods of time have been found to consist
      predominantly of fragments of the protein corresponding to residues 49-100, 49
      101, 53-100 and 53-101, derived largely from the partial acid hydrolysis of Asp-X
      peptide bonds. These internal fragments of HEWL encompass part of the beta-domain
      and all the residues forming the C-helix in the native protein, and contain two
      internal disulfide bridges Cys64-Cys80 and Cys76-Cys94. The complementary protein
      fragments, including helices A, B and D of the native protein, are not
      significantly incorporated into the network of fibrils, but remain largely
      soluble, in agreement with their predicted lower propensities to aggregate.
      Further analysis of the properties of different regions of HEWL to form amyloid
      fibrils was carried out by studying fragments produced by limited proteolysis of
      the protein by pepsin. Here, we show that only fragment 57-107, but not fragment
      1-38/108-129, is able to generate well-defined amyloid fibrils under the
      conditions used. This finding is of particular importance, as the beta-domain and
      C-helix of the highly homologous human lysozyme have been shown to unfold locally
      in the amyloidogenic variant D67H, which is associated with the familial cases of
      systemic amyloidosis linked to lysozyme deposition. The identification of the
      highly amyloidogenic character of this region of the polypeptide chain provides
      strong support for the involvement of partially unfolded species in the
      initiation of the aggregation events that lead to amyloid deposition in clinical
      disease.

PMID- 15236975
TI  - Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein:
      effects on amyloid fibril formation and chaperone activity.
AB  - alpha-Synuclein is a pre-synaptic protein, the function of which is not
      completely understood, but its pathological form is involved in neurodegenerative
      diseases. In vitro, alpha-synuclein spontaneously forms amyloid fibrils. Here, we
      report that alphaB-crystallin, a molecular chaperone found in Lewy bodies that
      are characteristic of Parkinson's disease (PD), is a potent in vitro inhibitor of
      alpha-synuclein fibrillization, both of wild-type and the two mutant forms (A30P
      and A53T) that cause familial, early onset PD. In doing so, large irregular
      aggregates of alpha-synuclein and alphaB-crystallin are formed implying that
      alphaB-crystallin redirects alpha-synuclein from a fibril-formation pathway
      towards an amorphous aggregation pathway, thus reducing the amount of
      physiologically stable amyloid deposits in favor of easily degradable amorphous
      aggregates. alpha-Synuclein acts as a molecular chaperone to prevent the stress
      induced, amorphous aggregation of target proteins. Compared to wild-type alpha
      synuclein, both mutant forms have decreased chaperone activity in vitro against
      the aggregation of reduced insulin at 37 degrees C and the thermally induced
      aggregation of betaL-crystallin at 60 degrees C. Wild-type alpha-synuclein
      abrogates the chaperone activity of alphaB-crystallin to prevent the
      precipitation of reduced insulin. Interaction between these two chaperones and
      formation of a complex are also indicated by NMR spectroscopy, size-exclusion
      chromatography and mass spectrometry. In summary, alpha-synuclein and alphaB
      crystallin interact readily with each other and affect each other's properties,
      in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone
      action.

PMID- 15236976
TI  - Mapping intersubunit interactions of the regulatory subunit (RIalpha) in the type
      I holoenzyme of protein kinase A by amide hydrogen/deuterium exchange mass
      spectrometry (DXMS).
AB  - Protein kinase A (PKA), a central locus for cAMP signaling in the cell, is
      composed of regulatory (R) and catalytic (C) subunits. The C-subunits are
      maintained in an inactive state by binding to the R-subunit dimer in a tetrameric
      holoenzyme complex (R(2)C(2)). PKA is activated by cAMP binding to the R-subunits
      which induces a conformational change leading to release of the active C-subunit.
      Enzymatic activity of the C-subunit is thus regulated by cAMP via the R-subunit,
      which toggles between cAMP and C-subunit bound states. The R-subunit is composed
      of a dimerization/docking (D/D) domain connected to two cAMP-binding domains
      (cAMP:A and cAMP:B). While crystal structures of the free C-subunit and cAMP
      bound states of a deletion mutant of the R-subunit are known, there is no
      structure of the holoenzyme complex or of the cAMP-free state of the R-subunit.
      An important step in understanding the cAMP-dependent activation of PKA is to map
      the R-C interface and characterize the mutually exclusive interactions of the R
      subunit with cAMP and C-subunit. Amide hydrogen/deuterium exchange mass
      spectrometry is a suitable method that has provided insights into the different
      states of the R-subunit in solution, thereby allowing mapping of the effects of
      cAMP and C-subunit on different regions of the R-subunit. Our study has localized
      interactions with the C-subunit to a small contiguous surface on the cAMP:A
      domain and the linker region. In addition, C-subunit binding causes increased
      amide hydrogen exchange within both cAMP-domains, suggesting that these regions
      become more flexible in the holoenzyme and are primed to bind cAMP. Furthermore,
      the difference in the protection patterns between RIalpha and the previously
      studied RIIbeta upon cAMP-binding suggests isoform-specific differences in cAMP
      dependent regulation of PKA activity.

PMID- 15236977
TI  - Pairwise interactions of the six human MCM protein subunits.
AB  - The eukaryotic minichromosome maintenance (MCM) proteins have six subunits, Mcm2
      to 7p. Together they play essential roles in the initiation and elongation of DNA
      replication, and the human MCM proteins present attractive targets for potential
      anticancer drugs. The six MCM subunits interact and form a ring-shaped
      heterohexameric complex containing one of each subunit in a variety of
      eukaryotes, and subcomplexes have also been observed. However, the architecture
      of the human MCM heterohexameric complex is still unknown. We systematically
      studied pairwise interactions of individual human MCM subunits by using the yeast
      two-hybrid system and in vivo protein-protein crosslinking with a non-cleavable
      crosslinker in human cells followed by co-immunoprecipitation. In the yeast two
      hybrid assays, we revealed multiple binary interactions among the six human MCM
      proteins, and a subset of these interactions was also detected as direct
      interactions in human cells. Based on our results, we propose a model for the
      architecture of the human MCM protein heterohexameric complex. We also propose
      models for the structures of subcomplexes. Thus, this study may serve as a
      foundation for understanding the overall architecture and function of eukaryotic
      MCM protein complexes and as clues for developing anticancer drugs targeted to
      the human MCM proteins.

PMID- 15236978
TI  - Why consider vaginal drug administration?
AB  - OBJECTIVE: To review the anatomy and physiology of the vagina, the merits of
      vaginal drug administration, and the currently available vaginal drug
      administration systems. DESIGN: Review of basic and clinical research. RESULT(S):
      Although clinicians commonly use topically administered drugs in the vagina, this
      route for systemic drug administration is somewhat novel. Experience with a
      variety of products demonstrates that the vagina is a highly effective site for
      drug delivery, particularly in women's health. The vagina is often an ideal route
      for drug administration because it allows for the administration of lower doses,
      steady drug levels, and less frequent administration than the oral route. With
      vaginal drug administration, absorption is unaffected by gastrointestinal
      disturbances, there is no first-pass effect, and use is discreet. Knowledge of
      anatomy, physiology, histology, and immunology of the vagina should allow
      clinicians to reassure their patients concerning this mode of delivery. Greater
      understanding and experience by clinicians should lead to increased use and
      acceptance of the vagina as a route for drug administration. CONCLUSION(S): The
      safety and efficacy of vaginal administration have been well established. The
      vaginal route of drug delivery is acceptable and may even be a preferable route
      of administration for many drugs, particularly hormones, whether for
      contraception or postmenopausal estrogen therapy.

PMID- 15236979
TI  - Timing intrauterine insemination either 33 or 39 hours after administration of
      human chorionic gonadotropin yields the same pregnancy rates as after
      superovulation therapy.
AB  - OBJECTIVE: To compare a short and long interval between hCG administration and
      IUI after superovulation for the treatment of infertility. DESIGN: Prospective,
      randomized clinical trial. SETTING: University hospital-based fertility clinic.
      PATIENT(S): Patients planning superovulation and IUI for the treatment of
      infertility. INTERVENTION(S): Patients with >or=2 years of infertility enrolled
      for superovulation and IUI treatment were randomized to IUI after a short (32-34
      hour) or long (38-40-hour) interval after hCG injection. Superovulation was
      accomplished with hMG or recombinant FSH, with dose adjustment until the
      maturation of two to five follicles, at which time hCG was given. Sperm was
      prepared with a gradient centrifugation technique, with IUI performed high up in
      the uterine fundus. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Of the
      348 patient cycles randomized, 270 treatment cycles were initiated. Eighty-one
      initiated cycles were canceled, leaving 189 completed randomized cycles from 75
      patients for analysis. Pregnancy rates were not significantly different between
      groups. There were pregnancies in 20 of the 96 short hCG-IUI interval cycles
      (21%) and in 14 of the 93 long hCG-IUI interval cycles (15%) (odds ratio = 0.673,
      95% confidence interval 0.297-1.518). CONCLUSION(S): Pregnancy rates are the same
      after superovulation therapy whether IUI is done after a short or a long interval
      after hCG injection.

PMID- 15236980
TI  - One versus two inseminations per cycle in intrauterine insemination with sperm
      from patients' husbands: a systematic review of the literature.
AB  - OBJECTIVE: To study the efficacy of performing two inseminations per cycle in IUI
      with husband's sperm compared with one insemination per cycle. DESIGN: Meta
      analysis. SETTING: Randomized and prospective trials comparing two inseminations
      vs. one insemination per cycle in IUI with husband's sperm, retrieved by MEDLINE
      and Cochrane Library searches (1966-2001) and a manual search of the abstracts of
      the European Society of Human Reproduction and Embryology and American Society
      for Reproductive Medicine annual meetings (1990-2001). PATIENT(S): A total of 865
      patients underwent 1156 cycles of IUI with husband's sperm. INTERVENTION(S):
      After different ovarian stimulation protocols, one or two inseminations were
      performed. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. Detected studies
      were tested for homogeneity. Because heterogeneity was observed, DerSimonian
      Laird relative risk with alleatory effects was used. RESULT(S): Six randomized
      and prospective trials involving 865 patients and 1156 cycles were identified.
      There was remarkable heterogeneity among the different studies concerning
      methodology, especially regarding ovarian cycle management and the timing of
      inseminations. Although the pregnancy rate per cycle was somewhat higher in the
      two-inseminations-per-cycle group (14.9% vs. 11.4%), there were no statistically
      significant differences (relative risk = 1.34; 95% confidence interval 0.90
      1.99). CONCLUSION(S): No significant differences were observed when two
      inseminations per cycle were performed, compared with one insemination. There was
      great heterogeneity concerning ovarian management and insemination timing. This
      heterogeneity hampered the analysis. We detected a better pregnancy rate with two
      inseminations vs. one insemination when clomiphene citrate with or without
      gonadotropins and 5000 IU of hCG were used. More studies are necessary to
      ascertain whether this is true or merely an artifact from the multiple subgroups
      analysis.

PMID- 15236981
TI  - Timing of intrauterine insemination: where are we?
AB  - Correct timing of insemination remains a controversial aspect of IUI cycles
      associated with ovarian hyperstimulation. Although it is currently believed that
      insemination at 32-38 hours after hCG administration provides the best results,
      clinical evidence supporting this conclusion is scarce. Double insemination might
      be an alternative, effective strategy, but studies on this topic are few,
      heterogeneous, and controversial.

PMID- 15236982
TI  - Randomized studies in intrauterine insemination.
AB  - Many factors in IUI might be critical to outcome. What realistically should be
      tested is another matter.

PMID- 15236983
TI  - For now, one well-timed intrauterine insemination is the way to go.
AB  - Two articles on pregnancy rates from superovulation and IUI in relation to the
      IUI protocol were reviewed. Results from a meta-analysis of IUI number (one vs.
      two) and from a randomized trial of IUI timing (33 hours vs. 39 hours after hCG
      administration) suggest that one well-timed insemination within several hours of
      ovulation represents a reasonable balance between efficacy and cost.

PMID- 15236986
TI  - Towards less confusing terminology in reproductive medicine: a proposal.
AB  - The use of the term 'infertility' and related terms in reproductive medicine is
      reviewed. Current terminology is found to be ambiguous, confusing, and
      misleading. We recommend that the fertility investigation report of a couple
      should consist of statements concerning description, diagnosis, and prognosis.
      The description concerns the duration of nonpregnancy before consulting the
      clinician. A system for prognostic grading is proposed. The fertility
      investigation report forms the basis for further action, including the
      possibility of waiting with treatment in case of almost normal or only slightly
      reduced fertility. The use of the terms 'infertility', 'subfertility', and
      'fecundity' is not necessary, and it is recommended to avoid them.

PMID- 15236987
TI  - How reliable are results from the semen analysis?
AB  - Based on the results of a number of studies that have evaluated the reliability
      of semen analysis testing, it would appear that there is a significant lack of
      standardization in the performance and reporting of semen analyses among
      laboratories. A large degree of variation and disagreement exists among different
      laboratories performing this test, and quality control procedures are not
      routinely performed in a majority of these laboratories. These observations
      significantly impact physicians who have to interpret and compare results among
      laboratories, who receive patients and test results referred from other clinics,
      or who have to rely on reference or other unknown laboratories for semen analysis
      testing.

PMID- 15236988
TI  - Prediction of an ongoing pregnancy after intrauterine insemination.
AB  - OBJECTIVE: To develop a prognostic model for the outcome of IUI. DESIGN:
      Retrospective cohort study. SETTING: Four fertility centers in The Netherlands.
      PATIENT(S): Couples of whom the female partners had a regular cycle and who had
      been treated with IUI. INTERVENTION(S): Intrauterine insemination with and
      without ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy.
      RESULT(S): Overall, 3371 couples were included who underwent 14968 cycles. There
      were 1229 (8.2%) pregnancies, of which 1000 (6.7%) pregnancies were ongoing.
      Logistic regression analysis demonstrated that increasing maternal age, longer
      duration of subfertility, presence of male factor subfertility, one-sided tubal
      pathology, endometriosis, uterine anomalies, and an increasing number of cycles
      were unfavorable predictors for an ongoing pregnancy. Cervical factor and the use
      of ovarian hyperstimulation were favorable predictors. The area under the
      receiver operating characteristic curve was 0.59. When couples were divided into
      four categories based on prognosis, the difference between the predicted and
      observed chance, that is, the calibration, was less than 0.5% in each of the four
      groups. CONCLUSION(S): Although our model had a relatively poor discriminative
      capacity, data on calibration showed that the selected prognostic factors allow
      distinction between couples with a poor prognosis and couples with a good
      prognosis. After external validation, this model could be of use in patient
      counseling and clinical decision making.

PMID- 15236989
TI  - Platelet-activating factor significantly enhances intrauterine insemination
      pregnancy rates in non-male factor infertility.
AB  - OBJECTIVE: To determine the efficacy of treating semen specimens with platelet
      activating factor (PAF) before IUI. DESIGN: Prospective randomized double-blinded
      study of PAF treatment of sperm for patients with a history of infertility
      undergoing IUI. SETTING: Private infertility center. INTERVENTION(S): Patients
      had ovulation induction therapy with clomiphene citrate (CC) or gonadotropin, two
      IUIs per month with PAF treatment. MAIN OUTCOME MEASURE(S): Clinical pregnancy
      rates. RESULT(S): There was a significant difference in IUI pregnancy rates per
      cycle between control (10/56; 17.9%) and PAF (14/47; 29.8%) treatment groups in
      the normal male study arm. There was a significant difference in cumulative IUI
      pregnancy rates between control (10/35; 28.6%) and PAF (14/26; 53.9%) patient
      groups in the normal male study arm. There was no significant difference in IUI
      pregnancy rates per cycle between control (12/124; 9.7%) and PAF (14/119; 11.8%)
      treatment groups in the male factor study arm. There was no significant
      difference in cumulative IUI pregnancy rates between control (12/46; 26.1%) and
      PAF (14/38; 36.8%) patient groups in the male factor study arm. There was a
      significant difference in overall cumulative IUI pregnancy rates between control
      (21/81; 25.9%) and PAF (27/64; 42.2%) patient groups. CONCLUSION(S): The
      inclusion of PAF into the IUI sperm wash procedure significantly improves
      pregnancy rates. However, the significant improvement can only be shown to affect
      men presenting with normal semen parameters.

PMID- 15236990
TI  - Influence of the abstinence period on human sperm quality.
AB  - OBJECTIVE: To determine the influence of ejaculatory abstinence on within-subject
      semen parameters and DNA fragmentation. DESIGN: Prospective study. SETTING:
      Private infertility institute and university-based research laboratory.
      PATIENT(S): Sixteen consenting male volunteers undergoing infertility
      investigation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Within-subject
      analysis of World Health Organization semen parameters and sperm DNA
      fragmentation and chromatin packaging after 1, 3, 5, and 8 days' abstinence.
      RESULT(S): Of 16 men recruited, data for 11 men were included for statistical
      analysis because 5 men did not strictly comply with abstinence criteria. Duration
      of abstinence had a statistically significant positive influence on sperm
      concentration and semen volume. Abstinence had no statistically significant
      influence on pH, viability, total and grade A motility, or morphology. The
      percentage of DNA fragmentation remained unchanged relative to abstinence. The
      percentage of sperm with immature chromatin was statistically significantly
      increased with 1 day of abstinence. CONCLUSION(S): This is the first study to
      report on within-subject semen parameter, DNA fragmentation, and chromatin
      packaging variations after specified target days of abstinence. Sperm numbers and
      semen volume increased with duration of abstinence. Abstinence did not influence
      pH, viability, morphology, total or grade A motility, or sperm DNA fragmentation.
      A short (24-hour) abstinence period negatively influenced chromatin quality.

PMID- 15236991
TI  - Sperm mitochondrial DNA depletion in men with asthenospermia.
AB  - OBJECTIVE: To determine the content of sperm mitochondrial DNA (mtDNA) in
      patients with asthenospermia or with poor sperm motility. DESIGN: Analysis of the
      content of mtDNA as the ratio between the amount of mtDNA and nuclear DNA by
      using a new concurrent polymerase chain reaction. SETTING: University hospital
      infertility center. PATIENT(S): Eighty-six men who sought infertility therapy.
      INTERVENTION(S): Moving characteristics of sperm were examined with a computer
      assisted semen analyzer. MAIN OUTCOME MEASURE(S): Sperm samples were classified
      into two groups, one with asthenospermia and the other with normal moving
      characteristics. The content of mtDNA in sperm was determined by polymerase chain
      reaction. We analyzed the mitochondrial mass by MitoTracker Green staining and
      analyzed DNA content with propidium iodide staining by flow cytometry. RESULT(S):
      A decrease in sperm mtDNA content was detected in patients with asthenospermia or
      with poor sperm motility (<20% motility). The relative mtDNA contents in the
      asthenospermia and normal groups were 7.2 +/- 1.3 (mean +/- SD, n = 23) and 74.1
      +/- 2.0 (n = 29), respectively. Lower intensities of propidium iodide staining
      were detected in patients with asthenospermia or poor motility, but there was no
      significant difference in MitoTracker Green staining between the sperm with
      different motility. CONCLUSION(S): We suggest that mtDNA content may serve as a
      useful indicator of sperm quality and that mtDNA depletion may play an important
      role in the pathophysiology of some male infertility.

PMID- 15236992
TI  - Use of the egg-share model to investigate the paternal influence on fertilization
      and embryo development after in vitro fertilization and intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To investigate whether sperm from different males can influence
      fertilization and embryo development. DESIGN: To use an egg-sharing model, in
      which the eggs from one woman are shared between herself and a recipient, and
      different spermatozoa are used to fertilize the eggs. SETTING: Assisted
      Conception Unit, Birmingham Women's Hospital, Edgbaston, United Kingdom.
      PATIENT(S): Infertile women undergoing egg sharing. INTERVENTION(S): In vitro
      fertilization (IVF). MAIN OUTCOME MEASURE(S): Fertilization rates and the mean
      day 2 or 3 embryo score (cell number X grade) were examined for egg-sharing
      pairs. A comparison was also made for pairs in which intracytoplasmic sperm
      injection (ICSI) and IVF was used as the insemination method. A paired samples t
      test was used to compare the sharer and recipient results. RESULT(S): Pregnancy
      rates did not differ between sharer and recipient couples. Interestingly, when
      comparing fertilization, there was a significant difference (P<.05) in favor of
      IVF over ICSI. When comparing embryo development between egg-sharing pairs, we
      found that approximately 30% of patients showed a difference in mean embryo score
      of >or= 5 in all embryo development and 14% in the quality of embryos available
      for transfer. CONCLUSION(S): We showed that the egg-sharing model is a successful
      alternative for the treatment of women who required donated eggs. More important,
      the egg-sharing model shows that, in a certain percentage of couples, differences
      in early embryo development are paternally influenced.

PMID- 15236993
TI  - Reduction of apoptosis and proliferation in endometriosis.
AB  - OBJECTIVE: To evaluate whether endometriosis could be related to an impaired
      balance between apoptosis and proliferation, two processes which could be
      modulated by hormonal status. DESIGN: Immunohistochemical study. SETTING:
      Academic research laboratory. INTERVENTION(S): Endometriotic samples obtained
      from peritoneum of women aged 26-40 years who were undergoing laparoscopy for
      pain or infertility. MAIN OUTCOME MEASURE(S): Apoptotic cells were detected with
      the use of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) assay. The production of p53 and bcl-2, estrogen and
      Progesterone (P) receptors, and cellular proliferation were assessed by
      immunohistochemistry in eutopic and ectopic endometria from 30 patients with
      endometriosis throughout the menstrual cycle. Results were compared with those
      from normal endometria from 15 fertile patients. RESULT(S): Endometriotic lesions
      were characterized by reduced TUNEL and p53 stainings and by enhanced bcl-2
      staining. No correlation between apoptosis and estrogen receptor or P receptor
      levels was found. A lower amount of steroid receptor was found in endometriotic
      tissues, without cyclic modulation, compared with the eutopic endometrium.
      CONCLUSION(S): Our results suggest that when endometrial tissue is located at
      ectopic locations, it differs from eutopic endometrium by its proliferation rate,
      steroid hormone levels, and markers of apoptosis. A reduced sensitivity of
      endometriotic cells to apoptosis could promote the dissemination and implantation
      of these cells to ectopic sites.

PMID- 15236994
TI  - CD10 immunohistochemical staining enhances the histological detection of
      endometriosis.
AB  - OBJECTIVE: To determine whether the use of CD10 immunohistochemistry in addition
      to hematoxylin and eosin (H&E) staining would increase the sensitivity of
      surgically suspected endometriosis lesions. DESIGN: Retrospective cohort study.
      SETTING: Tertiary care government research hospital. PATIENT(S): Thirty-one women
      with chronic pelvic pain. INTERVENTION(S): Immunohistochemical analysis for CD10
      was performed on 108 possible endometriotic lesions and in the corresponding
      endometrial biopsy samples obtained during laparoscopy. When CD10
      immunohistochemistry results were positive, the corresponding H&E section was
      reviewed to determine if the initial diagnosis should be revised. MAIN OUTCOME
      MEASURE(S): Histologic diagnosis of endometriosis by adjunctive use of CD10
      immunohistochemistry in conjunction with H&E-stained specimens. RESULT(S): In
      endometrial stroma, CD10 was consistently present. Of the 70 specimens judged
      negative initially by H&E staining, CD10 staining led to the diagnosis of
      endometriosis in 11. The addition of CD10 immunohistochemistry detected more
      positive endometriosis lesions than H&E staining alone (45% vs. 35%). In three
      women with minimal endometriosis at surgery but initially negative
      histopathology, CD10 immunohistochemistry changed the histologic diagnosis to
      endometriosis. CONCLUSION(S): The adjunctive use of CD10 immunohistochemistry
      improves diagnostic sensitivity for endometriosis, especially for women with
      minimal disease.

PMID- 15236995
TI  - Elevated angiogenin levels in the peritoneal fluid of women with endometriosis
      correlate with the extent of the disorder.
AB  - OBJECTIVE: To assess the release of angiogenin into peritoneal fluid in women
      with and without endometriosis by measuring its concentration with reference to
      disease stage, presence of red lesions, and phase of the menstrual cycle. DESIGN:
      Retrospective study. SETTING: Nagoya City University Hospital. PATIENT(S): Sixty
      four women with endometriosis (n = 38) and cystadenomas (n = 26) for whom surgery
      was scheduled in the proliferative or secretory phase of the menstrual cycle.
      INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or
      laparoscopy. MAIN OUTCOME MEASURE(S): Angiogenin concentrations in the peritoneal
      fluid, as measured by ELISA. RESULT(S): Angiogenin concentration in the
      peritoneal fluid was markedly elevated in the endometriosis patients (median 515
      ng/mL, interquartile range 151-1763 ng/mL) compared with the cystadenoma
      (control) patients (195 ng/mL, 98-324 ng/mL), with values correlating with the
      extent of the disease. No significant differences between the proliferative phase
      and the secretory phase were observed in either the controls or the endometriosis
      patients. CONCLUSION(S): The inflammation associated with endometriosis, through
      increasing levels of peritoneal fluid angiogenin, might promote angiogenesis for
      progression of the disease and correlate with the extent of the disorder.

PMID- 15236996
TI  - Elevations in peritoneal fluid macrophage migration inhibitory factor are
      independent of the depth of invasion or stage of endometriosis.
AB  - OBJECTIVE: To quantify levels of macrophage migration inhibitory factor (MIF) in
      the peritoneal fluid (PF) of women with endometriosis, and to correlate these
      levels with the extent of disease. DESIGN: Controlled clinical study. SETTING:
      Academic medical center. PATIENT(S): Peritoneal fluid samples were collected
      during laparoscopic surgery in 60 women with endometriosis and 16 controls
      undergoing tubal ligation; 52 of the women with endometriosis had received no
      hormonal treatment in the 6 months prior to surgery, while 8 were using
      gonadotropin-releasing hormone (GnRH) agonists. MAIN OUTCOME MEASURE(S):
      Peritoneal fluid migration inhibitory factor (PF MIF) levels. RESULT(S): Women
      with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL)
      than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF
      levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion
      (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF
      levels. Peritoneal fluid MIF levels did not vary significantly between the
      proliferative and secretory phases of the cycle, and did not distinguish women
      with endometriosis-associated infertility from women with endometriosis
      associated pain. CONCLUSION(S): Peritoneal fluid migration inhibitory factor
      levels are markedly elevated in women with endometriosis but are independent of
      the extent of disease.

PMID- 15236997
TI  - Prolongation of the follicular phase in in vitro fertilization results in a lower
      ongoing pregnancy rate in cycles stimulated with recombinant follicle-stimulating
      hormone and gonadotropin-releasing hormone antagonists.
AB  - OBJECTIVE: To assess the effect of altering the timing of hCG administration on
      ongoing pregnancy rates in patients stimulated with recombinant FSH (rec-FSH) and
      GnRH antagonists for IVF. DESIGN: Prospective, randomized, controlled trial.
      SETTING: Tertiary referral center. PATIENT(S): Four hundred thirteen patients
      undergoing IVF. INTERVENTION(S): Rec-FSH stimulation starting on day 2 of the
      cycle combined with daily GnRH antagonist starting on day 6 of stimulation.
      Patients were randomized to receive 10000 IU of hCG either as soon as at least
      three follicles were >or=17 mm on ultrasound (early-hCG group, 208 patients) or 2
      days later after this criterion was met (late-hCG group, 205 patients). MAIN
      OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): Fertilization rates and
      number and quality of embryos transferred did not differ between the two groups.
      However, a significantly lower ongoing pregnancy rate was present in the late-hCG
      as compared with the early-hCG group (25.0% vs. 35.6%, respectively).
      CONCLUSION(S): Prolongation of the follicular phase in patients stimulated with
      rec-FSH and GnRH antagonists for IVF does not affect oocyte or embryo quality but
      is associated with a significantly lower ongoing pregnancy rate.

PMID- 15236998
TI  - Cryopreservation of human embryos at the morula stage and outcomes after
      transfer.
AB  - OBJECTIVE: To evaluate the survival rate of human morula embryo freezing and the
      morphological alterations during freezing, during and after thawing, and their
      applications in embryo selection. DESIGN: Retrospective observational study.
      SETTING: Private infertility clinic. PATIENT(S): Consecutive patients under age
      39 undergoing frozen morula embryo transfers from December 1999 to May 2003.
      INTERVENTION(S): Embryo freezing was performed at the morula stage. Embryo thaw
      and post-thaw ETs were conducted on the same day, which is equivalent to a day 4
      ET. MAIN OUTCOME MEASURE(S): Morphological alterations during freezing and
      thawing and after thawing. Post-thaw embryo survival rates, transferable rates,
      pregnancy rates, and implantation rates. RESULT(S): Morula embryos showed
      reversed morphological alterations during the freezing process; these alterations
      were recovered during thawing or shortly after the thawing. Post-thaw survival
      rates showed no significant difference between any of the morula substages.
      However, embryos scored as grade 3, which represented good quality, had
      significantly higher post-thaw survival and transferable rates than grade 2 and 1
      embryos. Patients who received at least one grade 3 embryo had significantly
      higher pregnancy rates, implantation rates, and ongoing/live birth rates than
      other groups. CONCLUSION(S): An acceptable survival rate can be achieved after
      cryopreservation of human morula embryos, and morphological alterations that
      occur during and shortly after an embryo thaw can be a feasible index for
      determining viable embryos.

PMID- 15236999
TI  - Luteinizing hormone concentrations after gonadotropin-releasing hormone
      antagonist administration do not influence pregnancy rates in in vitro
      fertilization-embryo transfer.
AB  - OBJECTIVE: To determine the impact of circulating LH concentrations during
      controlled ovarian hyperstimulation on the outcome of IVF. DESIGN: Retrospective
      study. SETTING: University hospital. PATIENT(S): Two-hundred seventy women who
      had a short stimulation protocol with GnRH antagonist and ovarian stimulation
      with recombinant FSH (rFSH). INTERVENTION(S): GnRH antagonist and rFSH were
      administered SC; blood samples were collected on the day of GnRH antagonist
      administration, 1 day after, and on the day of hCG administration. MAIN OUTCOME
      MEASURE(S): A threshold of 0.5 IU/L on the day of hCG was chosen to discriminate
      between women with LH concentrations <or=0.5 IU/L (group A, n = 119) or >0.5 IU/L
      (group B, n = 151). RESULT(S): The two groups were comparable with regard to the
      clinical parameters. In group A, significantly lower LH concentrations were
      observed on day 9 of the cycle and on the day of hCG administration. The numbers
      of oocytes retrieved, embryos obtained, and embryos cryopreserved were
      significantly higher in group A compared with group B. The proportion of clinical
      pregnancies was similar in the two groups (21.1% vs. 22.7 % per ET).
      CONCLUSION(S): In GnRH antagonist and rFSH protocols, suppressed serum LH
      concentrations do not have any influence on the final stages of follicular
      maturation, pregnancy rates, or outcomes.

PMID- 15237000
TI  - Nitric oxide is associated with poor embryo quality and pregnancy outcome in in
      vitro fertilization cycles.
AB  - OBJECTIVE: To evaluate the association between follicular and serum nitric oxide
      (NO) levels and embryo development and outcome in IVF. DESIGN: Prospective, case
      control study. SETTING: University hospital, tertiary medical center. PATIENT(S):
      Eighteen patients with tubal or peritoneal factor infertility and 18 female
      partners from couples with male factor infertility underwent controlled ovarian
      stimulation and IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S):
      Controlled ovarian stimulation and oocyte retrieval followed by IVF/ICSI and
      embryo culture. MAIN OUTCOME MEASURE(S): Degree of fragmentation of embryos and
      pregnancy rate. RESULT(S): Higher follicular NO levels were associated with
      advanced fragmentation of embryos. Follicular soluble Fas could not prevent
      embryo fragmentation. Higher serum NO levels were found among nonpregnant
      patients with tubal or peritoneal factor infertility. No elevated serum NO levels
      were found in the female partners from couples with male factor infertility.
      CONCLUSION(S): Up-regulation of serum NO is associated with implantation failure
      in patients with tubal or peritoneal factor infertility.

PMID- 15237001
TI  - DNA microarray-based analysis of single nucleotide polymorphisms may be useful
      for assessing the risks and benefits of hormone therapy.
AB  - OBJECTIVE: To determine what percentage of women can be given individualized
      counseling based on genetic information, as single nucleotide polymorphisms
      (SNPs) are associated with risks and benefits of estrogen therapy and hormone
      therapy such as thrombosis, myocardial infarction, breast cancer, and bone
      protection. DESIGN: Cross-sectional study. SETTING: Academic research
      institution. PATIENT(S): A consecutive series of 2,507 perimenopausal and
      postmenopausal women. INTERVENTION(S): Peripheral venous puncture and multiplex
      polymerase chain reaction on a microarray system. MAIN OUTCOME MEASURE(S):
      Analysis of 22 SNPs of 17 genes: AGTMet235Thr, APOECys112Arg, APOEArg158Cys,
      COMTVal158Met, CYP17-34T>C, CYP191558C>T, CYP19Arg264Cys, CYP1A16235T>C,
      CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1Asn453Ser, HSD17B1-27A>C, ER-alphaIVS
      401T>C, prothrombin20210G>A, factor V Leiden, eNOS-786T>C, eNOSGlu298Asp,
      MRSer810Leu, MTHFR677C>T, PAI 15G>4G, SRD5A2Val89Leu, and VDRb>B. RESULT(S):
      Among the women in the study, 66% had at least two homozygous mutant SNPs of
      interest. A thrombophilic disposition was found in 9.9% of women, and 23% of
      women had at least two SNPs associated with an increased risk of breast cancer
      (COMT, CYP17, CYP19, CYP1A1, and CYP1B1). The SNPs predisposing women to
      cardiovascular pathologies (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3%
      of women. Carriage of SNPs predisposing to early postmenopausal bone loss and
      osteoporosis (ER-alpha and VDR) were found in 26.7% of women. CONCLUSION(S):
      These data suggest that the assessment of SNPs associated with risks and benefits
      of estrogen/hormone therapy may be a new means to individualize counseling about
      and prescription of estrogen/hormone therapy in up to 66% of women.

PMID- 15237002
TI  - Lack of sleep disturbance from menopausal hot flashes.
AB  - OBJECTIVE: To determine whether hot flashes produce disordered sleep in
      symptomatic postmenopausal women. DESIGN: Controlled laboratory study. SETTING:
      Healthy volunteers in a university medical center. PATIENT(S): Symptomatic and
      asymptomatic postmenopausal women and premenopausal women, all of similar ages
      (46-51 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sleep
      electroencephalogram recordings, sternal skin conductance to record hot flashes,
      multiple sleep latency test to assess sleepiness, simple and divided attention
      performance tests, sleep and fatigue questionnaires. RESULT(S): Nineteen women
      were not selected for the following reasons: seven failed the drug screen, two
      had sleep apnea and periodic limb movements, one had periodic limb movements
      alone, two had body mass index (BMI) >30, one had hypertension, and six
      asymptomatic women had hot flashes in the laboratory. There were no significant
      group differences on any sleep stage measure. For example, for cycling vs.
      symptomatic vs. asymptomatic women: total sleep time, 6.9 +/- 0.7, 7.0 +/- 0.4,
      7.0 +/- 0.4 hours; percentage stage 1 (light) sleep, 9.3% +/- 4.2%, 10.4% +/-
      2.5%, 10.5% +/- 3.9%; number of brief arousals, 89.6 +/- 30.1, 111.9 +/- 45.8,
      99.4 +/- 22.2; number of awakenings, 4.8 +/- 3.3, 6.7 +/- 2.1, 6.9 +/- 3.5. An
      average of 5.2 +/- 2.9 (+/-SD, range 1-18) hot flashes/night occurred in the
      symptomatic women. Of arousals occurring within 2 minutes of a hot flash, 46.7%
      occurred before, 46.7% occurred after, and 5.6% occurred simultaneously. Of
      awakenings occurring within 2 minutes of a hot flash, 55.2% occurred before,
      40.0% after, and 5% simultaneously. There were no significant group differences
      on the multiple sleep latency test or any performance test or questionnaire
      measure. CONCLUSION(S): These data provide no evidence that hot flashes produce
      sleep disturbance in symptomatic postmenopausal women. Previous reports of
      increased sleep disturbance at menopause may be due to disorders that were
      screened out, such as sleep apnea and drug use.

PMID- 15237003
TI  - Endometrial effects of long-term treatment with phytoestrogens: a randomized,
      double-blind, placebo-controlled study.
AB  - OBJECTIVE: To determine the effects of 5 years of treatment with soy
      phytoestrogens on histological characteristics of endometrium in postmenopausal
      women. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING:
      Centre of Perinatal and Reproductive Medicine, Department of Gynecological,
      Obstetrical, and Pediatric Sciences, University of Perugia, Italy. PATIENT(S):
      Three hundred seventy-six postmenopausal healthy women, all with intact uterus.
      INTERVENTION(S): Women were distributed in two different groups using randomized
      criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones
      per day) for 5 years; group B (n = 197) patients received identical appearing
      placebo tablets for 5 years. MAIN OUTCOME MEASURE(S): Results of endometrial
      histology from biopsies obtained at baseline, 30 months, and 5 years after the
      beginning of the treatment. RESULT(S): Two hundred ninety-eight women completed
      the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy
      percent of women undergoing treatment with soy phytoestrogens had an endometrium
      classified as atrophic or nonassessable versus 81% receiving placebo. The
      occurrence of endometrial hyperplasia was significantly higher in group A (3.37%
      vs. 0%). CONCLUSION(S): Long-term treatment (up to 5 years) with soy
      phytoestrogens was associated with an increased occurrence of endometrial
      hyperplasia. These findings call into question the long-term safety of
      phytoestrogens with regard to the endometrium.

PMID- 15237004
TI  - A prospective evaluation of the effects of salpingectomy on endometrial
      lymphocyte clusters in patients with hydrosalpinges.
AB  - OBJECTIVE: To investigate the effect of hydrosalpinges on embryo implantation.
      DESIGN: Prospective study. SETTING: Private fertility and university hospitals.
      PATIENT(S): Eighteen patients with unilateral or bilateral hydrosalpinges who
      underwent salpingectomy. INTERVENTION(S): Pre- and posttreatment endometrial
      biopsies for immunohistochemical evaluation. MAIN OUTCOME MEASURE(S): Pre- and
      posttreatment lymphocyte populations in endometrial samples, evaluated by
      immunohistochemical identification. RESULT(S): Endometrial samples from
      pretreatment exhibited small lymphocytic clusters of CD3+, CD8+, CD4+, granzyme B
      positive, and CD56+. After salpingectomy, the numbers of cluster lesions were
      significantly decreased. CONCLUSION(S): Because a characteristic distribution of
      lymphocytes in endometrium with hydrosalpinges was found, activation of T/NK
      (natural killer) lymphocytes in endometrium might be involved in the impairment
      of embryo implantation in cases of hydrosalpinges.

PMID- 15237005
TI  - Reproductive performance before and after abdominal myomectomy: a retrospective
      analysis.
AB  - OBJECTIVE: To evaluate the results of abdominal myomectomy for intramural and
      subserosal fibroids and to identify factors that influence the reproductive
      outcome after surgery. DESIGN: Retrospective analysis of a case series. SETTING:
      An academic department specializing in gynecologic surgery. PATIENT(S): A total
      of 72 women with intramural and subserosal fibroids submitted to abdominal
      myomectomy who wished to conceive after surgery. INTERVENTION(S): Data were
      collected on clinical characteristics, surgical features, and obstetric history
      before and after surgery. MAIN OUTCOME MEASURE(S): Conception rate, pregnancy
      loss, and live birth rate before and after surgery, as well as postoperative
      probability of conception according to selected clinical and fibroid
      characteristics. RESULT(S): Conception rate was 28% before myomectomy and 70%
      after surgery. The corresponding figures were 69% and 25% for pregnancy loss and
      30% and 75% for live birth rate, respectively. Age <30 years and number of
      fibroids removed were the only significant and independent predictors of
      obstetric outcome by multivariate analysis. CONCLUSION(S): Our results suggest
      that abdominal myomectomy might improve reproductive outcome in patients with
      intramural and subserosal fibroids. The reproductive performance was particularly
      good when the patients were younger than 30 years and had a single myoma to
      remove.

PMID- 15237006
TI  - Treatment of dysfunctional uterine bleeding: patient preferences for endometrial
      ablation, a levonorgestrel-releasing intrauterine device, or hysterectomy.
AB  - OBJECTIVE: To investigate patient preferences for endometrial ablation and a
      levonorgestrel-releasing intrauterine device (IUD) as alternatives to
      hysterectomy in the treatment of dysfunctional uterine bleeding. DESIGN:
      Comparative study based on structured interviews. SETTING: A large teaching
      hospital with 500 beds in the Netherlands. PATIENT(S): Ninety-six patients who
      were scheduled for endometrial ablation, 25 patients who were scheduled for
      hysterectomy, and 23 patients who were scheduled for a levonorgestrel-releasing
      IUD were interviewed. All of the women had dysfunctional uterine bleeding.
      INTERVENTION(S): Patients were asked to state their most significant complaints
      and their reasons for choosing a particular treatment. Subsequently, the
      preference for endometrial ablation and a levonorgestrel-releasing IUD as
      alternatives to hysterectomy was assessed during a structured interview. Women
      were informed about the advantages and disadvantages of all three treatment
      options. Patients rated their preferences according to different hypothetical
      success rates. The success rates after endometrial ablation and levonorgestrel
      releasing IUD were varied until patients found an acceptable treatment outcome.
      MAIN OUTCOME MEASURE(S): Patient preference of endometrial ablation and the
      levonorgestrel-releasing IUD over hysterectomy. RESULT(S): The main reason for
      the treatment of choice differed between the three groups. Most of the patients
      in the hysterectomy group wanted a definite solution to their problems, whereas
      patients in the levonorgestrel-releasing IUD group and in the ablation group put
      greater emphasis on a minimally invasive intervention with or without a short
      hospital stay. In women undergoing ablation, 70% of the patients preferred this
      treatment and the levonorgestrel-releasing IUD to hysterectomy in cases in which
      the success rate of noninvasive treatment was presumed to be 50%. In women having
      a levonorgestrel-releasing IUD inserted, 95% of the patients preferred this
      approach over hysterectomy in cases in which the success rate of this device was
      presumed to be 50%, whereas 35% of patients preferred ablation over hysterectomy
      in cases in which the success rate of ablation was presumed to be 50%. In women
      undergoing hysterectomy, 30% would have opted for ablation and 45% would have
      opted for a levonorgestrel-releasing IUD in cases in which success rates were
      50%. Of patients who opted for hysterectomy, however, 60% stated that they would
      have preferred a noninvasive treatment if the success rate of this type of
      treatment were >80%. CONCLUSION(S): A majority of the patients who had
      dysfunctional uterine bleeding and who were scheduled for an endometrial ablation
      or a levonorgestrel-releasing IUD were inclined to take a risk of 50% likelihood
      of treatment failure to avoid a hysterectomy. As a consequence, research of
      treatment for dysfunctional uterine bleeding should focus on this 50% success
      level.

PMID- 15237007
TI  - Accelerated endometrial maturation in the luteal phase of cycles utilizing
      controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone
      agonists versus antagonists.
AB  - OBJECTIVE: To evaluate the endometrium obtained during the luteal phase of
      controlled ovarian hyperstimulation (COH) cycles utilizing gonadotropin-releasing
      hormone (GnRH) antagonists, and to compare these findings with those obtained in
      cycles utilizing a GnRH agonist and with artificial cycles among recipients.
      DESIGN: Prospective evaluation of oocyte donors. SETTING: University-based in
      vitro fertilization (IVF) center. PATIENT(S): Fifteen oocyte donors undergoing
      standard COH were enrolled in 1 of 3 COH groups, and 40 recipients of oocyte
      donation were used as a control group. INTERVENTION(S): Controlled ovarian
      hyperstimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S): Histological
      dating of endometrial biopsies, serum estradiol (E(2)) and progesterone levels.
      RESULT(S): On the day of oocyte retrieval, endometrial maturation was advanced by
      an average of 5.8 +/- 0.4 days in the antagonist group and 5.9 +/- 0.7 days in
      the agonist group. This advancement persisted on day 7 postoocyte retrieval.
      Serum progesterone levels were elevated before human chorionic gonadotropin (hCG)
      administration, but remained similar in both groups. CONCLUSION(S): Controlled
      ovarian hyperstimulation is associated with elevated progesterone levels in the
      late follicular phase and accelerated endometrial maturation in the subsequent
      luteal phase. No significant differences exist between preretrieval serial serum
      progesterone levels and luteal phase endometrial histology between cycles
      utilizing GnRH agonists or antagonists.

PMID- 15237008
TI  - Offspring created as a result of donor insemination: a study of family
      relationships, child adjustment, and disclosure.
AB  - OBJECTIVE: To compare the quality of family relationships and children's
      socioemotional adjustment in families created by donor insemination where parents
      tended either toward disclosure or nondisclosure. DESIGN: A study of 46 families
      with a child aged 4-8 years who was conceived through donor insemination. The
      study used standardized interview data from mothers and fathers, teachers, and
      the children themselves. SETTING: An assisted conception unit endorsing openness.
      PATIENT(S): Parents and their 4- to 8-year-old child conceived through donor
      insemination. INTERVENTION(S): Parents were interviewed, and children were
      administered psychological tests. MAIN OUTCOME MEASURE(S): Interviews and
      questionnaires assessing the quality of the marital relationship, parent-child
      relationships, and child psychological adjustment. RESULT(S): Mothers from
      disclosing families reported significantly less frequent and less severe
      arguments with their children and considered their children to show a lower level
      of conduct problems and to be less of a strain. The disclosing parents viewed
      themselves as more competent at parenting. CONCLUSION(S): The differences that
      were identified indicated more positive parent-child relationships in the
      disclosing than in the nondisclosing families. However, this did not represent
      dysfunctional relationships in the nondisclosing families but instead reflected
      particularly positive ratings in the disclosing group.

PMID- 15237009
TI  - Comparison of basal follicle-stimulating hormone versus the clomiphene citrate
      challenge test for ovarian reserve screening.
AB  - OBJECTIVE: To compare the value of basal follicle-stimulating hormone (FSH)
      measurement vs. the clomiphene citrate challenge test (CCCT) in predicting the
      ability to achieve a pregnancy in women who are undergoing infertility treatment.
      DESIGN: Meta-analysis. SETTING: All studies that evaluated either basal FSH or
      the CCCT for determining the likelihood of pregnancy. PATIENT(S): Infertility
      population undergoing treatment, which was defined as patients undergoing
      ovulation induction, IUI, or in vitro fertilization (IVF). INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Diagnostic test characteristics were calculated and
      pooled using standard methods. Inability to achieve a pregnancy with treatment
      was considered as the "disease." RESULT(S): Twelve studies on basal FSH (with
      6296 patients, mean age 33.8) and seven studies on the CCCT (with 1352 patients,
      mean age 34.5) fit our criteria and were analyzed. For basal FSH and the CCCT,
      the sensitivities were 6.6% (95% confidence interval [CI] 5.9, 7.3%) and 25.9%
      (95% CI 23.0, 29.0%), respectively, and specificities were 99.6% (95% CI 99.1,
      99.9%) and 98.1% (95% CI 96.5, 99.1%), respectively. For "disease" prevalence
      ranging from 40%-100%, for basal FSH and the CCCT, the positive predictive values
      ranged from 91.7%-100% and 90.1%-100%, respectively, and negative predictive
      values ranged from 61.5%-0.0% and 66.5%-0.0%, respectively. CONCLUSION(S): Basal
      FSH and the CCCT are similar in predicting the ability to achieve a clinical
      pregnancy in women undergoing infertility treatment. With either test, a normal
      result is not useful, but an abnormal result virtually confirms that pregnancy
      will not occur with treatment.

PMID- 15237010
TI  - Hormonal factors and the risk of invasive ovarian cancer: a population-based case
      control study.
AB  - OBJECTIVE: To examine the influence of hormone-related factors on the risk of
      invasive epithelial ovarian cancer (ovarian cancer). DESIGN: Population-based
      case-control study using in-person interviews. SETTING: Academic department of
      preventive medicine. PATIENT(S): Four hundred seventy-seven ovarian cancer
      patients and 660 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Numbers of and ages at births, oral contraceptive use, and use of menopausal
      hormone therapy. RESULT(S): Compared with nulliparous women, women whose only
      (last) birth was after age 35 years had an estimated 51% (95% confidence
      interval: 21%-70%) reduction in risk. If this birth occurred earlier, the
      reduction in risk was progressively less. Additional (earlier) births reduced the
      risk further. Oral contraceptive use also reduced risk. Increased body mass index
      increased risk, but this effect was confined to localized disease and is likely
      to be a diagnostic bias, as a consequence of other problems associated with being
      overweight and in itself having no etiological significance. CONCLUSION(S): If
      the major protective effect of a late birth can be confirmed, our most
      challenging task will be to understand the mechanism to develop a chemoprevention
      approach to exploit this finding.

PMID- 15237011
TI  - Essure: a new device for hysteroscopic tubal sterilization in an outpatient
      setting.
AB  - OBJECTIVE: To evaluate the results of hysteroscopic placement of an intratubal
      device for permanent birth control in 85 women in an outpatient setting. DESIGN:
      Prospective, observational study. SETTING: Private university hospital.
      PATIENT(S): Eighty-five premenopausal women who asked for tubal sterilization by
      hysteroscopy between July 2002 and July 2003. INTERVENTION(S): Hysteroscopic
      placement of titanium-dacron intratubal devices in an outpatient setting. MAIN
      OUTCOME MEASURE(S): Procedure feasibility without anesthesia, success rate of
      device implantation, patient satisfaction, and confirmation of correct placement.
      RESULT(S): Successful placement was achieved in 81 patients (95%). Mean time
      elapsed between the start of hysteroscopy, placement of devices, and removal of
      optics was 9 minutes (range, 1-35 minutes). No intraoperative or postoperative
      complications were detected. Of 81 patients, 75 (93%) had abdominal x-ray
      performed at the third month; bilateral correct placement was confirmed in all of
      them. CONCLUSION(S): Essure is a safe, effective, and minimally aggressive
      procedure with satisfactory patient acceptance that does not require anesthesia
      or hospitalization. It seems to be a good alternative to laparoscopic tubal
      sterilization.

PMID- 15237012
TI  - Influence of multiple transrectal electroejaculations on semen parameters and
      intracytoplasmic sperm injection outcome.
AB  - OBJECTIVE: To compare semen parameters and intracytoplasmic sperm injection
      (ICSI) outcome in spinal cord-injured subjects who underwent single (group 1) or
      multiple (group 2) electroejaculations before ICSI. DESIGN: Prospective,
      randomized, controlled study. SETTING: Department of gynecology, obstetrics, and
      pediatric science in a reproductive medicine unit at a major Italian university.
      PATIENT(S): Thirty-four healthy women with a male partner with SCI who were
      seeking assisted reproduction services. INTERVENTION(S): Transrectal
      electroejaculation, controlled ovarian hyperstimulation, and ICSI. MAIN OUTCOME
      MEASURE(S): Sperm concentration, morphology, and motility and fertilization and
      pregnancy rates after ICSI. RESULT(S): Sperm was successfully retrieved in 94.1%
      of cases. In male subjects who underwent multiple electroejaculations,
      statistically significant improvements in sperm concentration and total sperm
      motility rate were observed. The overall fertilization rate was 63.6%. The number
      of oocytes retrieved and injected was comparable between the two groups. A total
      of nine clinical pregnancies were achieved. The pregnancy rate was statistically
      significantly higher in group 2 (n = 6/16; 37.5%) than in group 1 (n = 3/16;
      18.75%). CONCLUSION(S): These data suggest that multiple electroejaculation has a
      positive effect on semen parameters and ICSI outcome.

PMID- 15237013
TI  - Combining the uterine depletion procedure and myomectomy may be useful for
      treating symptomatic fibroids.
AB  - OBJECTIVE: To evaluate the therapeutic results of premyomectomy uterine depletion
      for the treatment of symptomatic fibroids, compared with myomectomy only. DESIGN:
      Controlled, clinical study without randomization. SETTING: University-affiliated
      tertiary referral center. PATIENT(S): Four hundred eighty-six women with
      symptomatic fibroids warranting surgical treatment and who wished to retain their
      uteri. INTERVENTION(S): Ligation of the uterine arteries was performed by either
      an abdominal or a laparoscopic approach before myomectomy. MAIN OUTCOME
      MEASURE(S): Operation time, intraoperative blood loss, postoperative improvement
      of symptoms, and recurrence rates of fibroids. RESULT(S): Of 342 women with
      pathology-confirmed fibroids who were included in the study, 108 received
      myomectomy only (group I), and 234 underwent the uterine depletion procedure
      followed by myomectomy (group II). Average blood loss was 250 +/- 132.5 mL for
      group I and 50 +/- 26.9 mL for group II. For patients with menorrhagia, 79 (84%)
      of 94 women in group I experienced complete resolution; all of the 194 women
      (100%) in group II had resolution within 2 months of surgery. The recurrence rate
      of ultrasound-confirmed fibroids was 19.4% (21 of 108) in group I and 0% in group
      II. Of the sexually active patients who were not using contraception, 50% (49 of
      98) in group I and 37.5% (15 of 40) in group II had a live birth. CONCLUSION(S):
      This study demonstrates the value of uterine depletion before myomectomy for the
      management of patients with symptomatic fibroids. The procedure reduced blood
      loss during the operation, resulted in complete resolution of fibroid-related
      menorrhagia, and has the potential to prevent fibroid recurrence. Fertility
      capacity was apparently not compromised by this new treatment approach.

PMID- 15237014
TI  - Pregnancy after cryopreservation of donor oocytes and preimplantation genetic
      diagnosis of embryos in a patient with ovarian failure.
AB  - OBJECTIVE: To describe the successful use of preimplantation genetic diagnosis to
      assess the prevalence of meiotic errors after oocyte cryopreservation in an
      oocyte donation cycle. DESIGN: Case report. SETTING: Private IVF center.
      PATIENT(S): A 42.6-year-old patient with ovarian failure. INTERVENTION(S): A
      donor oocyte IVF cycle with cryopreservation of oocytes followed by thaw,
      fertilization of oocytes, preimplantation genetic diagnosis for selective
      aneuploidy, and ET. MAIN OUTCOME MEASURE(S): Preimplantation genetic analysis of
      chromosomes 13,16,18, 21,22, X, and Y with fluorescence in-situ hybridization.
      RESULT(S): The recipient's initial serum beta-hCG level was 196 mIU/mL 15 days
      after oocyte retrieval. An initial ultrasound at the sixth week of gestation
      revealed two gestational sacs. A second ultrasound 1 week later showed a
      monochorionic twin in sac A and a singleton pregnancy in sac B. Fetal cardiac
      activity was visualized for all gestations. CONCLUSION(S): This case illustrates
      the feasibility of cryopreservation of donor oocytes combined with
      preimplantation genetic diagnosis for clinical use in those settings where there
      may be an increased risk of spindle-related abnormalities.

PMID- 15237015
TI  - Successful pregnancies in the setting of exaggerated endometrial thickness.
AB  - OBJECTIVE: To report successful pregnancies in the setting of exaggerated
      endometrial thickness. DESIGN: Case report. SETTING: Two infertility practices.
      PATIENT(S): Two IVF patients. INTERVENTION(S): IVF and ET. MAIN OUTCOME
      MEASURE(S): Endometrial thickness on the days of hCG injection, oocyte retrieval,
      and ET. RESULT(S): Two successful twin pregnancies, each after the transfer of
      two embryos, in the setting of an endometrial thickness of 16 mm in one case and
      20 mm in the other. CONCLUSION(S): This report illustrates the possibility for a
      successful outcome in the setting of an exaggerated endometrial thickness,
      including for the first time a value of 20 mm on the day of egg retrieval.

PMID- 15237016
TI  - Gonadotropin treatment of an azoospermic patient with a Y-chromosome
      microdeletion.
AB  - OBJECTIVE: To report on the treatment with recombinant FSH of an azoospermic
      normogonadotropic patient with a Y-chromosome microdeletion. DESIGN: Case report.
      SETTING: An assisted reproduction center. PATIENT(S): A 32-year-old patient with
      azoospermia. INTERVENTION(S): Histological testicular biopsy, Y-chromosome
      screening, FSH treatment, and intracytoplasmic sperm injection. MAIN OUTCOME
      MEASURE(S): Fertilization, embryo development, pregnancy, and delivery.
      RESULT(S): After 6 months of treatment with gonadotropins, a small number of
      spermatozoa were found in the patient's ejaculate and used for IVF, resulting in
      a successful twin pregnancy and the delivery of two healthy girls. CONCLUSION(S):
      In this study, treatment with gonadotropins promoted the spermatogenesis process
      and led to the production of spermatozoa in a normogonadotropic azoospermic
      patient.

PMID- 15237017
TI  - Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone,
      progesterone, and 17beta-estradiol on thrombospondin-1 mRNA in Ishikawa cells.
AB  - Abberant endometrial angiogenesis has been implicated in abnormal endometrial
      bleeding in users of progestin-only contraceptives. We believe that a possible
      cause is an underexpression of thrombospondin-1 (TSP-1). Progestins had less
      effects on TSP-1 mRNA compared to P, in Ishikawa cells, and this difference in
      TSP-1 expression by individual progestins may be associated with the irregular
      bleeding seen in women using progestin-only contraception.

PMID- 15237018
TI  - Administration of gonadotropin-releasing hormone antagonist from day 1 of
      stimulation in in vitro fertilization.
AB  - After administration of GnRH antagonist from day 1 of stimulation for IVF, 12.1
      cumulus oocyte complexes were retrieved (95% confidence interval [CI], 10.6
      13.6), 1.9 embryos were transferred (95% CI, 1.7-2.0), and 2.4 embryos were
      cryopreserved (95% CI, 1.7-3.1). Stimulation for 8.8 days (95% CI, 8.4-9.2) with
      recombinant FSH resulted in an ongoing implantation rate of 26.5% (95% CI, 17.1
      35.9) and an ongoing pregnancy rate of 39.7% per started cycle (95% CI, 30.1
      50.8) and of 42.4% per ET (95% CI, 32.3-53.1).

PMID- 15237019
TI  - Slow fetal heart rate may predict pregnancy outcome in first-trimester threatened
      abortion.
AB  - Two hundred forty pregnant women presented with first-trimester threatened
      abortion were examined by transvaginal ultrasound. Women with a slow fetal heart
      rate of less than 120 beats per minute may eventually be at increased risk for
      pregnancy loss.

PMID- 15237020
TI  - Nerve fibers in ovarian dermoid cysts and endometriomas.
AB  - No nerve fibers are found in endometriomas or in the endometrioma-containing
      ovaries. These findings are consistent with our previous report that no
      correlation exists between the presence of nerve fibers and endometriosis.

PMID- 15237021
TI  - Epidermal growth factor contamination and concentrations of intact human
      chorionic gonadotropin in commercial preparations.
AB  - It is well-known that many urinary-derived human chorionic gonadotropin (hCG)
      preparations contain a variety of contaminating agents that may influence the
      efficacy and possible safety of their application. Herein, we report the finding
      of epidermal growth factor (EGF) contamination and high hCG beta core levels in
      two leading brands of hCG - findings that will promote the use of recombinant hCG
      instead of the cruder, urinary-derived formulations.

PMID- 15237022
TI  - Controlled natural in vitro fertilization may be an alternative for patients with
      repeated unexplained implantation failure and a high uterine natural killer cell
      count.
AB  - Patients with a history of repeated and unexplained implantation failure after
      IVF-embryo transfer and a high uterine natural killer cell count during estrogen
      progestin treatment may benefit from controlled natural IVF-ET.

PMID- 15237023
TI  - Serum testosterone levels in patients with nonmosaic Klinefelter syndrome after
      testicular sperm extraction for intracytoplasmic sperm injection.
AB  - We measured testosterone levels in 24 patients with nonmosaic Klinefelter
      syndrome before and at 6 and 12 months after conventional or microdissection
      testicular sperm extraction. Testosterone levels decreased after surgery by
      either technique, and they did not recover to baseline concentrations, even when
      using less invasive microdissection techniques.

PMID- 15237024
TI  - A danazol-loaded intrauterine device decreases dysmenorrhea, pelvic pain, and
      dyspareunia associated with endometriosis.
AB  - A danazol-loaded intrauterine device (IUD) containing 300-400 mg of danazol was
      inserted for 6 months in a group of women (n = 18) (median age 36.6 years; age
      range: 30 to 46 years) with a histologic diagnosis of endometriosis, referred for
      recurrent pelvic pain. Dysmenorrhea, dyspareunia, and pelvic pain significantly
      decreased after the first month, with a persistent effect during the 6 months of
      IUD insertion. These results show that a danazol-loaded IUD is an effective
      conservative therapy for patients with endometriosis-related pelvic pain.

PMID- 15237025
TI  - Conventional in vitro fertilization versus intracytoplasmic sperm injection for
      sibling oocytes in couples with mild oligoteratoasthenozoospermia and couples
      with normal sperm.
AB  - Use of intracytoplasmic sperm injection (ICSI) in couples with mild
      oligoteratoasthenozoospermia decreases the complete fertilization failure rate
      and may also reduce the embryo cleavage rate. ICSI does not benefit couples with
      normal sperm.

PMID- 15237026
TI  - Insulin levels, insulin resistance, and leptin levels are not associated with the
      development of ovarian hyperstimulation syndrome.
AB  - Insulin levels, insulin resistance, and leptin levels were evaluated in 47 women
      who developed ovarian hyperstimulation syndrome (OHSS) after participation in
      assisted reproduction technologies programs and in 47 matched controls who did
      not develop such a complication. Analysis of the results in relation to
      underlying polycystic ovarian syndrome and hyperinsulinemia revealed no
      association of insulin levels, insulin resistance, and leptin levels with the
      development of OHSS.

PMID- 15237027
TI  - Timing of sperm capacitation appears to be programmed according to egg
      availability in the female genital tract.
AB  - The time course of the level of A23187-induced acrosome reaction between human
      and rabbit spermatozoa was compared. It was extended in the former (a periodic
      ovulator) and short in the latter (an induced ovulator). This finding suggests
      that the capacitated state is programmed to maximize the prospects that an
      ovulated egg will meet spermatozoa in the best functional state.

PMID- 15237028
TI  - Effect of gonadotropin-releasing hormone agonist treatment on growth hormone
      responses in women with polycystic ovary syndrome.
AB  - This study supports the importance of regulatory role of the E(2) in growth
      hormone secretion in women with polycystic ovary syndrome, showing for the first
      time a different weight-related sensitivity of the growth-hormone axis to
      hypoestrogenism induced by gonadotropin-releasing hormone agonist.

PMID- 15237030
TI  - Treatment of endometriosis without aromatase inhibitors.

PMID- 15237033
TI  - Conveying and discussing uncertainty- looking in both directions.

PMID- 15237034
TI  - Conveying and discussing uncertainty- looking in both directions.

PMID- 15237035
TI  - Prognostic value of pronuclear morphology.

PMID- 15237037
TI  - Open electronic debate--even your obituary fails to escape peer review!

PMID- 15237039
TI  - Open electronic debate-even your obituary fails to escape peer review!

PMID- 15237040
TI  - Current evaluation of amenorrhea.
AB  - Amenorrhea is the absence or abnormal cessation of the menses. Primary and
      secondary amenorrhea describe the occurrence of amenorrhea before and after
      menarche, respectively.

PMID- 15237042
TI  - Chronic suicidality and borderline personality.
AB  - Suicidal ideation is a complex clinical event. In this article, acute suicidal
      ideation is compared with chronic suicidal ideation, specifically their different
      meanings, relationships with Axis I and Axis II disorders, intrapsychic
      functions, approaches to assessment, and interventions. The potential risks of
      acute hospitalization of the chronically suicidal borderline personality disorder
      patient are discussed as well as a longitudinal, multidimensional treatment
      strategy for the chronically suicidal individual.

PMID- 15237044
TI  - Is hospitalization useful for suicidal patients with borderline personality
      disorder?
AB  - This article examines the value of hospitalization for chronically suicidal
      patients with borderline personality disorder (BPD). One in 10 of these patients
      will eventually complete suicide. However, this outcome is not readily
      predictable. Hospitalization is of unproven value for suicide prevention and can
      often produce negative effects. Day treatment is an evidence-based alternative to
      full admission. Chronic suicidality can best be managed in an outpatient setting.

PMID- 15237043
TI  - Suicidal behavior in borderline personality disorder: prevalence, risk factors,
      prediction, and prevention.
AB  - Suicidal behavior is frequent in patients with borderline personality disorder
      (BPD); at least three-quarters of these patients attempt suicide and
      approximately 10% eventually complete suicide. Borderline patients at greatest
      risk for suicidal behavior include those with prior attempts, comorbid major
      depressive disorder, or a substance use disorder. Comorbidity with major
      depression serves to increase both the number and seriousness of the suicide
      attempts. Hopelessness and impulsivity independently increase the risk of
      suicidal behavior, as does a turbulent early life and the presence of antisocial
      traits. In summary, because BPD is frequently complicated by suicidal behavior,
      clinicians must avoid the mistake of thinking that a pattern of repeated attempts
      indicates little desire to die. Clinicians have an important role in preventing
      suicide attempts and completed suicides by understanding the risk factors.

PMID- 15237045
TI  - Suicide, suicide litigation, and borderline personality disorder.
AB  - In the category of malpractice liability affecting mental health practitioners of
      all disciplines, malpractice based on suicide is the leading claim by a
      significant margin. Our discussion here will be organized in two sections. First,
      we consider the theory, practice, and psychology of malpractice litigation itself
      in relation to suicide. Second, we describe how those basic principles apply to
      patients with borderline personality disorder.

PMID- 15237046
TI  - An open clinical trial of cognitive therapy for borderline personality disorder.
AB  - Although borderline personality disorder (BPD) is a major public health concern,
      psychotherapeutic trials have been limited. The present uncontrolled clinical
      trial examines whether cognitive therapy for BPD is associated with significant
      improvement on measures of psychopathology. A total of 32 patients with BPD, who
      also reported suicide ideation or who engaged in self-injury behavior, received
      weekly cognitive therapy sessions over a 1-year period as described by Layden et
      al. (1993). The results revealed significant and clinically important decreases
      on measures of suicide ideation, hopelessness, depression, number of borderline
      symptoms and dysfunctional beliefs at termination and 18-month assessment
      interviews. Implications for further research with this difficult-to-treat
      patient population are discussed.

PMID- 15237047
TI  - Personality disorders, depression, and coping styles in Argentinean bulimic
      patients.
AB  - This study investigates the coping styles of bulimic patients with personality
      disorders (PDs) and the effects of the level of depression on the relations
      between PDs and coping. The sample consisted of 75 Argentinean bulimic
      outpatients engaged in treatment. Patients completed the SCID II (Structural
      Interview for DSM IV-Personality Disorders), COPE (Coping Inventory), and the SCL
      90-R (Symptom Checklist-90-Revised). No differences in the coping styles of
      bulimic patients with or without a PD were found. However, when three specific
      PDs were considered-Avoidant, Obsessive-Compulsive, or Borderline PDs-clear
      differences in the coping styles of the bulimics were found. However, the
      differences disappeared when depression was controlled. Regarding the severity of
      the three specific PDs, coping styles were only found to be associated with the
      Avoidant PD. Depression showed to affect the relations between coping styles and
      two specific PDs-Avoidant and Borderline PDs-in bulimic patients.

PMID- 15237049
TI  - The Many Aspects of Clinical Cellular Analysis.

PMID- 15237048
TI  - Clinicians' personality descriptions of prototypic personality disorders.
AB  - Many studies have indicated close convergence of the DSM-IV personality disorders
      and the five-factor model (FFM) of personality functioning. However, questions
      have been raised concerning the ability of clinicians to describe personality
      disorders in terms of the FFM. This study developed a FFM description by
      practicing clinicians of each DSM-IV personality disorder. Clinicians rated a
      prototypic case of each DSM-IV personality disorder in terms of the FFM. These
      ratings, which achieved excellent reliability, were then averaged to produce a
      consensus FFM profile for each personality disorder. The consensus ratings showed
      good agreement with previous research that examined both researchers' and
      clinicians' application of the FFM to prototypic cases of personality disorders.
      These results suggest that clinicians can conceptualize and apply the FFM to
      personality disorders in a consistent way. The results further suggest that the
      FFM may provide a richer and more comprehensive description of personality
      difficulties than the current DSM-IV personality disorder categories.

PMID- 15237050
TI  - HIV/AIDS prevention in "Indian country": current practice, indigenist etiology
      models, and postcolonial approaches to change.
AB  - Many tribal and urban American Indians and Alaska Native communities have
      initiated HIV/AIDS prevention and treatment services. The richness, depth, and
      scope of these efforts, however, are not well known and have not been
      sufficiently documented in the academic literature. In this article we assess the
      strengths and weakness of the published literature using the constructs of the
      socioecological framework. We discuss the need to apply an "indigenist" etiology
      paradigm to HIV/AIDS risk and protection. Finally, we define and discuss the
      varied postcolonial approaches to HIV/AIDS prevention, treatment, and healing.

PMID- 15237051
TI  - Components of successful HIV/AIDS case management in Alaska Native villages.
AB  - Case management is a valuable support service for HIV/AIDS patients, but little
      is known about the elements of case management that contribute to success for
      Alaska Natives living in remote rural villages. This study used qualitative data
      from 18 key informants (social services/health workers, family members, and
      tribal leaders) to identify the elements of successful case management. Two major
      categories dominated the analysis. First, the case management organization
      possessed attributes, such as location, coordination, and support for
      professionals, that contributed to a positive case management experience. Second,
      the case manager had both knowledge/professional skills and values with personal
      capabilities that contributed to positive experiences. These components of
      successful case management can be integrated into existing and future case
      management programs for Alaska Natives to improve client level outcomes.

PMID- 15237052
TI  - Surveillance systems monitoring HIV/AIDS and HIV risk behaviors among American
      Indians and Alaska Natives.
AB  - Few published reports describe patterns of occurrence of HIV/AIDS among American
      Indian/Alaska Native (AI/AN) people nationally. Data from national surveillance
      systems were examined to describe the spread of HIV/AIDS and the prevalence of
      HIV-related risk behaviors among AI/AN people. These data indicate that HIV/AIDS
      is a growing problem among AI/AN people and that AI/AN youth and women are
      particularly vulnerable to the continued spread of HIV infection.

PMID- 15237053
TI  - Health and support service utilization patterns of American Indians and Alaska
      Natives diagnosed with HIV/AIDS.
AB  - The purpose of this analysis is twofold: to examine the types of health and
      support services provided by CARE Act funded providers to American Indians/Alaska
      Natives and to compare the characteristics and service utilization patterns for
      this group with those of individuals from other racial/ethnic groups. We present
      an analysis of the demographic characteristics, service utilization, and health
      outcomes of all HIV-infected clients who received services in five geographic
      areas at agencies that were funded through the Ryan White Comprehensive AIDS
      Resources Emergency (CARE) Act. Standard chi-square tests were used to test for
      statistically significant differences (p <.05) between the demographic
      characteristics and service utilization patterns of matched pairs of HIV-positive
      American Indian/Native Alaskans with HIV-positive individuals of other racial and
      ethnic backgrounds. Individuals were matched on gender, age, insurance, AIDS
      diagnosis, and site. Other data examined include client characteristics (income,
      homelessness, HIV exposure category, and source of health care), health
      indicators (CDC-defined disease stage, CD4+ counts, substance abuse and
      psychiatric illness) and service utilization (medical care; mental health
      treatment/counseling; substance abuse treatment/counseling; case management;
      dental care; housing, food, emergency financial, and transportation assistance,
      and buddy/companion and client advocacy services). There were no statistically
      significant differences between the two groups for HIV exposure category, CD4
      count, substance abuse problem, and being homeless and in their likelihood to
      receive medical care, mental health or substance abuse treatment/counseling,
      dental care, food, emergency financial, and transportation assistance, as well as
      buddy/companion and client advocacy services. They were more likely (55% vs. 46%)
      to receive case management services than the matched individuals from other
      racial/ethnic groups. They were also more likely to receive housing assistance
      (35% vs. 25%). The analysis provides evidence that when individuals are matched
      on key demographic and health characteristics, few differences remain between HIV
      positive American Indians/Native Alaskans and other racial/ethnic groups. The two
      exceptions are case management and housing assistance. The significantly higher
      use of case management is not surprising, given the emphasis by American
      Indians/Alaska Natives on traditional Native American case management case
      management. In contrast, the significantly higher use of housing assistance by
      American Indians/Alaska Natives was unexpected. Exploring the potential need for
      housing assistance among all American Indians/Alaska Natives served by the Ryan
      White CARE Act needs to be considered.

PMID- 15237054
TI  - Urging others to be healthy: "intravention" by injection drug users as a
      community prevention goal.
AB  - "Intravention," prevention activities that are conducted by and sustained through
      ongoing actions of members of communities-at-risk, is an appropriate goal for HIV
      intervention activities. Data from 120 injection drug users in a Brooklyn, New
      York, neighborhood that has seen decreases in HIV prevalence among IDUs and
      little HIV diffusion to young adults indicate that most of them have recently (3
      months) urged other people to engage in one or more self-protective actions.
      These data suggest that the common image of IDUs as simply being sources of
      social and medical problems is inaccurate. Research is needed into how to create
      and diffuse "communities of intravention; " and we suggest that behavioral
      interventions be evaluated for their success or failure at creating outward
      focused health communication by participants as well as for their impact on
      individual risk behaviors.

PMID- 15237055
TI  - Long-term effects of syringe exchange on risk behavior and HIV prevention.
AB  - The purpose of this study was to assess stability of population-level injection
      risk behavior over time among participants in a syringe exchange program and
      compare factors affecting syringe sharing at two points in time. Participants of
      the Tacoma Syringe Exchange Program were interviewed in 1997 and 2001 using audio
      computer assisted self-interviewing technology. In each wave of data collection,
      a random cross section of participants was recruited and interviewed, with no
      attempt made to follow respondents over time. Rates of injection risk behavior
      remained stable across the 4-year period, despite increases in factors associated
      with syringe sharing. Homelessness, rates of depression symptoms, and injection
      of amphetamines all increased from 1997 to 2001. The central factors associated
      with syringe sharing in both 1997 and 2001 were depression symptoms and the
      interaction of younger age with amphetamine injection. The data indicate that the
      exchange has been able to stabilize risk among a high-risk population for a
      substantial period of time. This study confirms previous findings that SEPs can
      play a significant role in the prevention of HIV in marginal and impoverished
      communities in the United States.

PMID- 15237056
TI  - The urgent need for HIV and hepatitis prevention in drug treatment programs in
      Hungary.
AB  - We assess HIV and hepatitis testing and counseling in drug treatment programs in
      Hungary, a country with low rates of HIV but high rates of hepatitis C among
      injection drug users. The official context of drug treatment programs is
      described, and using key informants from representative drug treatment programs,
      the practice of HIV and hepatitis testing and counseling in such programs is
      assessed. Although HIV testing and counseling occurs, testing and counseling for
      hepatitis B and C are rare, especially in outpatient settings, and sexual risk in
      the drug use context is ineffectively addressed by treatment programs. Drug
      treatment centers are not adequately addressing the need to provide either HIV or
      hepatitis prevention services. There is an urgent need for preventing HIV and
      related infections among drug users by integrating HIV and hepatitis B and C
      prevention with drug treatment.

PMID- 15237058
TI  - Dying young: cues from the courts.

PMID- 15237059
TI  - Evaluation of a method to reduce over-the-counter medication dosing error.
AB  - OBJECTIVES: To introduce a simple method of dosing over-the-counter medication in
      a home setting using a color-coding concept and to compare dosing deviation from
      recommended dosage using the color-coded method with dosing deviation using
      conventional package labeling. DESIGN: Randomized controlled clinical trial.
      SETTING: Pediatric emergency center at a tertiary care medical center.
      PARTICIPANTS: A sample of 101 caregivers of children with nonemergent complaints
      separated into 2 groups. One group used a conventional dosing method and the
      other group used a color-coded method to determine and measure a dose of
      acetaminophen for their child. MAIN OUTCOME MEASURES: For both dose determination
      and dose measuring, percentage of deviation from recommended acetaminophen dosage
      was calculated and compared between the 2 groups. RESULTS: There was no
      significant difference in sociodemographic characteristics between the 2 groups.
      How-ever, for dose determination, the average deviation (25.8% vs 1.7%) and
      median deviation (1% vs 0%) from recommended dosage were both higher for the
      group using conventional methods compared with the group using the color-coded
      method. The Wilcoxon rank sum test indicated that the median deviation was
      significantly different between the 2 groups (P<.001). Similar results were
      obtained for dose measuring. The average deviation (29% vs 0.5%) and the median
      deviation (17.2% vs 0%) from recommended dosage were higher for the group using
      conventional methods compared with the group using the color-coded method. The
      median deviation was also significantly different between the 2 groups (P<.001).
      CONCLUSION: This study suggests a marked improvement in caregivers' ability to
      correctly determine and measure an over-the-counter medication for their child
      using a color-coded method compared with conventional methods.

PMID- 15237060
TI  - Does a color-coded method for measuring acetaminophen doses reduce the likelihood
      of dosing error?

PMID- 15237061
TI  - Sex differences in adolescent exposure to alcohol advertising in magazines.
AB  - OBJECTIVES: To measure girls' and boys' exposure to alcohol advertising in
      magazines and to compare this exposure with that of legal-age persons. DESIGN,
      SETTING, AND SUBJECTS: Alcohol advertisements (N = 6239) in 103 national
      magazines for which placement, audience, and cost data for 2001 and 2002 were
      available, categorized by year, beverage type, and brand. Placement and
      readership (age and sex) data generated estimates of media exposure for the age
      groups 12 to 20, 21 to 34, and 21 years and older. MAIN OUTCOME MEASURES: Gross
      rating points, an advertising industry standard measure of the level of media
      exposure of a given population, and gross rating point ratios comparing exposure
      of different demographic groups. RESULTS: Alcohol companies spent 590.4 million
      US dollars to place 471 beer and ale advertisements (8%), 4748 distilled spir-its
      advertisements (76%), 116 low-alcohol refresher advertisements (2%), and 904
      advertisements for wine (14%) in magazines in 2001 and 2002. In 2002, underage
      youth saw 45% more beer and ale advertising, 12% more distilled spirits
      advertising, 65% more low-alcohol refresher advertising, and 69% less advertising
      for wine than persons 21 years and older. Girls aged 12 to 20 years were more
      likely to be exposed to beer, ale, and low-alcohol refresher advertising than
      women in the group aged 21 to 34 or women in the group aged 21 years and older.
      Girls' exposure to low-alcohol refresher advertising increased by 216% from 2001
      to 2002, while boys' exposure increased 46%. CONCLUSION: Exposure of underage
      girls to alcohol advertising is substantial and increasing, pointing to the
      failure of industry self-regulation and the need for further action.

PMID- 15237062
TI  - Randomized trial of brief office-based interventions to reduce adolescent alcohol
      use.
AB  - OBJECTIVE: To determine whether office-based interventions change adolescents'
      alcohol beliefs and alcohol use. DESIGN: Randomized, controlled trial. SETTING:
      Five managed care group practices in Washington, DC. PARTICIPANTS: Consecutive 12
      to 17-year-olds (N = 409) seeing primary care providers (N = 26) for general
      check-ups. Most of the adolescents (79%) were African American, 44% were male,
      and 16% currently drank. INTERVENTIONS: Usual care (Group I), adolescent priming
      with alcohol self-assessment just prior to check-up (Group II), adolescent
      priming and provider prompting with adolescent self-assessment and brochure
      (Group III). MAIN OUTCOME MEASURES: Adolescent alcohol beliefs at exit interview
      and self-reported behaviors at 6- and 12-month follow-up. RESULTS: At exit
      interview, Groups II and III reported that less alcohol was needed for impaired
      thinking and a greater intent to drink alcohol in the next 3 months than Group I.
      At 6 months, Group III reported more resistance to peer pressure to drink, and
      Groups II and III reported more bingeing than Group I. At 1-year follow-up,
      controlling for baseline levels, Groups II (odds ratio [OR], 3.44; 95% confidence
      interval [CI], 1.44-6.24) and III (OR, 2.86; CI, 1.13-7.26) reported more
      bingeing in the last 3 months than Group I. Group II reported more drinking in
      the last 30 days (OR, 2.31; CI, 1.31-4.07) and in the last 3 months (OR, 1.76;
      CI, 1.12-2.77) than Group I. CONCLUSION: Brief office-based interventions were
      ineffective in reducing adolescent alcohol use but may increase adolescent
      reporting of alcohol use.

PMID- 15237063
TI  - Risk markers for poor developmental attainment in young children: results from a
      longitudinal national survey.
AB  - OBJECTIVE: To evaluate social and environmental determinants of poor
      developmental attainment among preschool children by means of longitudinal data
      from a population-based sample of Canadian children. DESIGN: Secondary analysis
      of data from cycles 1 (1994-1995) and 2 (1996-1997) of the National Longitudinal
      Survey of Children and Youth using a cohort design with 2-year follow-up.
      PARTICIPANTS: A total of 4987 children aged 1 to 5 years at baseline, whose
      biological mother completed risk factor information and who were included in both
      cycles. MAIN OUTCOME MEASURES: Poor developmental attainment (developing
      unusually slowly) was defined as scores more than 1 SD below the age-standardized
      mean for the Motor and Social Development Scale, revised Peabody Picture
      Vocabulary Test, or Canadian Achievement Tests in mathematics and
      reading/comprehension, depending on the child's age. RESULTS: The prevalence of
      sustained poor developmental attainment after 2 years of follow-up was 4.6%.
      Factors found to be associated with poor developmental attainment included male
      sex (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.10-1.70), maternal
      depression (OR, 1.64; 95% CI, 1.25-2.15), low maternal education (OR, 1.57; 95%
      CI, 1.19-2.08), maternal immigrant status (OR, 1.93; 95% CI, 1.38-2.71), and
      household low income adequacy (OR, 1.43; 95% CI, 1.11-1.83). CONCLUSIONS: Having
      a mother who has symptoms of depression, has low education, or is an immigrant,
      and living in a household with low income adequacy increase the risk of poor
      developmental attainment in children aged 1 to 5 years. The notable risks
      associated with these factors indicate them as possible targets for screening and
      interventions to prevent poor developmental attainment.

PMID- 15237064
TI  - Lactation among adolescent mothers and subsequent bone mineral density.
AB  - OBJECTIVE: To investigate the association of breastfeeding during adolescence
      with bone mineral density (BMD) during young adulthood. METHODS: Secondary
      analysis of data from the National Health and Nutrition Examination Survey III, a
      nationally representative cross-sectional survey conducted from 1988 through
      1994, was performed. The BMDs for 5 regions of the proximal femur as measured by
      dual energy x-ray absorptiometry were compared for 5 groups of women aged 20 to
      25 years (n = 819); the groups included those who had been: (1) adolescent
      mothers and had breastfed (n = 94), (2) adolescent mothers and had not breastfed
      (n = 151), (3) mothers who first gave birth as adults and breastfed (n = 67), (4)
      mothers who first gave birth as adults and had not breastfed (n = 89), and (5)
      nulliparous (n = 418). SUDAAN software was used to account for the complex
      sampling design of the National Health and Nutrition Examination Survey. Adjusted
      mean differences in BMD were estimated using least-squares linear regression.
      RESULTS: During young adulthood, women who breastfed during adolescence had
      higher adjusted BMDs, which was statistically significant in 4 of the 5 regions,
      than those who had not breastfed (total proximal femur area difference, 0.049
      gm/cm(2) [95% confidence interval, 0.002-0.095]) and BMDs equivalent to
      nulliparous women (total proximal femur area difference, 0.024 gm/cm(2) [95%
      confidence interval, -0.023 to 0.071]). Adjusting also for obstetric variables,
      women who breastfed during adolescence had higher BMDs in all 5 regions compared
      with their peers who had not breastfed (total proximal femur area difference,
      0.053 gm/cm(2) [95% confidence interval, 0.029-0.077]). CONCLUSIONS: In this
      nationally representative sample, breastfeeding by adolescent mothers was
      associated with greater BMD in the proximal femur during young adulthood.
      Lactation was not found to be detrimental and may be protective to the bone
      health of adolescent mothers.

PMID- 15237066
TI  - Does parental involvement predict new sexually transmitted diseases in female
      adolescents?
AB  - BACKGROUND: African American female adolescents living in low-income urban areas
      are at increased risk for sexually transmitted diseases. OBJECTIVE: To determine
      if high levels of perceived parental supervision and communication were
      associated with reduced gonorrhea (GC) and chlamydia (CT) incidence in low
      income, African American, sexually experienced female adolescents, aged 14 to 19
      years, attending urban health clinics. DESIGN: A prospective cohort study was
      used to determine the predictive value for high levels of parental supervision
      and communication on GC and CT infection in 158 adolescent females. Multiple
      logistic regression analysis explored the association between incident infection
      and perceived parental supervision and perceived parental communication while
      controlling for relevant demographic and behavioral factors (age, religious
      involvement, school enrollment, a 2-parent household, having a main sex partner,
      and having concurrent sex partners). RESULTS: When adjusted for age and baseline
      GC and CT infection, high levels of perceived parental supervision were
      associated with reduced GC and CT incidence (adjusted odds ratio, 0.06; 95%
      confidence interval, 0.01-0.31). High levels of perceived parental communication
      were not associated with reduced GC and CT incidence (adjusted odds ratio, 0.55;
      95% confidence interval, 0.21-1.42). CONCLUSIONS: The link between parental
      supervision and disease acquisition is particularly valuable because it provides
      evidence that parental supervision can result in lower sexually transmitted
      disease rates in urban high-prevalence populations. This is important for
      interventions designed to increase parental involvement as a strategy for
      promoting protective sexual behaviors in female adolescents because it indicates
      that increased parental involvement can also influence subsequent disease
      acquisition.

PMID- 15237065
TI  - Neighborhood predictors of concealed firearm carrying among children and
      adolescents: results from the project on human development in Chicago
      neighborhoods.
AB  - BACKGROUND: Previous studies of concealed firearm carrying among children and
      adolescents have focused on individual risk factors. OBJECTIVE: To identify
      features of neighborhoods associated with concealed firearm carrying among a
      representative sample of youth from Chicago, Ill. DESIGN: Cross-sectional
      analysis of individual- and neighborhood-level data collected by the Project on
      Human Development in Chicago Neighborhoods. SETTING: Families and neighborhoods
      in Chicago. PARTICIPANTS: Population-based sample of 1842 multiethnic youth aged
      9 to 19 years and the 218 neighborhoods in which they resided. Main Outcome
      Measure Whether youth had ever carried a concealed firearm. RESULTS: Lifetime
      estimates for concealed firearm carrying were 4.9% for males and 1.1% for
      females. We found that youth in safer and less disordered neighborhoods were less
      likely than youth in unsafe and more disordered neighborhoods to carry concealed
      firearms. Specifically, multilevel nonlinear regression models identified a
      positive association between concealed firearm carrying and (1) community
      members' ratings of neighborhoods as unsafe for children; (2) neighborhood social
      disorder; and (3) neighborhood physical disorder. Neighborhood collective
      efficacy was negatively associated with concealed firearm carrying. Models
      controlled for neighborhood economic indicators and individual and family factors
      associated with the carrying of concealed firearms by youth. CONCLUSIONS: Youth
      are less likely to carry concealed firearms in areas where there is less violence
      and increased safety. Interventions to improve neighborhood conditions such as
      increasing safety, improving collective efficacy, and reducing social and
      physical disorder may be efficacious in preventing firearm use and its associated
      injuries and death among youth.

PMID- 15237067
TI  - Incidence of occult bacteremia among highly febrile young children in the era of
      the pneumococcal conjugate vaccine: a study from a Children's Hospital Emergency
      Department and Urgent Care Center.
AB  - BACKGROUND: The optimal diagnostic approach to and management of well-appearing,
      highly febrile young children has been a matter of debate owing to the
      possibility of clinically inapparent, or occult, bacteremia (OB). The most common
      causative organism of OB is Streptococcus pneumoniae. Universal immunization with
      a heptavalent pneumococcal conjugate vaccine (PCV7) has recently been
      implemented, but there are limited data on the impact of this vaccine on the
      incidence of OB. OBJECTIVE: To evaluate the incidence of OB in the era of routine
      use of PCV7. METHODS: We conducted a retrospective cohort study of highly febrile
      (temperature, 39 degrees C) children between the ages of 2 months and 36 months
      who had blood cultures performed in the emergency department or urgent care
      center between December 11, 2001, and March 5, 2003, and were discharged to home
      at the time of the initial visit. RESULTS: Of 329 blood cultures obtained from
      children who met inclusion criteria and did not meet exclusion criteria, 3
      (0.91%; 95% confidence interval, 0%-1.9%) yielded a pathogenic bacterium; all
      were S pneumoniae. Neither an elevated total white blood cell count, an elevated
      absolute neutrophil count, nor an increased percentage of bands was highly
      predictive of OB. Blood cultures positive for organisms were more commonly due to
      contaminants (4; 95% confidence interval, 0%-2.4%) than pathogens. CONCLUSIONS:
      In the PCV7 era, OB is uncommon in highly febrile children 2 to 36 months of age.
      With continued use of PCV7, the routine practice of obtaining blood cultures and
      complete blood cell counts may no longer be indicated in previously healthy, well
      appearing, highly febrile children 2 to 36 months of age, particularly those who
      have received at least 1 dose of PCV7.

PMID- 15237068
TI  - Glycemic patterns detected by continuous subcutaneous glucose sensing in children
      and adolescents with type 1 diabetes mellitus treated by multiple daily
      injections vs continuous subcutaneous insulin infusion.
AB  - OBJECTIVE: To compare glycemic patterns by mode of therapy in children with type
      1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS).
      DESIGN: Open randomized crossover comparing 3(1/2) months of multiple daily
      injections (MDI) and continuous subcutaneous insulin infusion (CSII). SETTING:
      Tertiary care, university-affiliated medical center. Patients Twenty-three
      children and adolescents with type 1 diabetes mellitus. INTERVENTIONS: The CGMS
      was applied for 72 hours after 1 month and at the end of each study arm. MAIN
      OUTCOME MEASURES: Hemoglobin A(1c) levels and glucose level profiles were
      compared between the 2 study arms and the 2 sensor applications for each arm.
      RESULTS: The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0%
      [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were
      significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01
      and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03
      and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03),
      but 24-hour duration and area under the curve for hyperglycemia were similar.
      Compared with the first CGMS reading in each arm, the second had a longer mean
      duration of postprandial within-target glucose levels (P =.04), tendency for
      lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal
      hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia
      (P =.04). CONCLUSIONS: Intensive treatment with CSII seemed to be associated with
      slightly better prebreakfast, postprandial, and within-target glucose profiles
      than MDI, as well as a smaller area under the curve for hypoglycemia. Lower
      hypoglycemia-related variables in the second sensor reading in each arm indicate
      that the CGMS may serve as an educational tool to decrease the rate and magnitude
      of hypoglycemia.

PMID- 15237069
TI  - Secondhand smoke exposure, smoking hygiene, and hospitalization in the first 18
      months of life.
AB  - BACKGROUND: Recognizing the suboptimal public health effects of a complete
      cessation strategy for parents and child caregivers who smoke, some researchers
      have called for a harm reduction approach; however, the evidence remains scanty
      and controversial. OBJECTIVE: To examine the effects of secondhand smoke and
      smoking hygiene on infant health and related health care costs during the first
      18 months of life. METHODS: We conducted prospective follow-up on 8327 newborns
      during April and May of 1997 for 18 months in a population-based birth cohort of
      infants from Hong Kong, China. MAIN OUTCOME MEASURES: Number of hospital
      admissions, adjusted odds ratios for ever hospitalization for each secondhand
      smoke exposure variable, and corresponding population attributable risks.
      RESULTS: Most secondhand smoke exposure came from fathers and other household
      contacts, whereas only 2.8% of mothers smoked postpartum. The odds ratio of ever
      hospitalization due to all illnesses combined for infants living in a household
      with any (maternal, paternal, or other) smoker who was smoking at least 3 m away
      from the infant, as reported by a parent, was 1.00 (95% confidence interval, 0.88
      1.13) compared with those in a smoke-free household. The corresponding odds ratio
      for infants living with any smoker at home with poor smoking hygiene (<3 m away)
      was 1.28 (95% confidence interval, 1.07-1.52), which translated into 2.8% of all
      inpatient episodes in the first year of life, representing an additional 616
      admissions. CONCLUSIONS: Hospital admission was significantly more likely among
      infants exposed to secondhand smoke if it was accompanied by poor smoking
      hygiene. Harm reduction strategies should be rigorously adhered to when complete
      cessation is not possible.

PMID- 15237070
TI  - Pediatricians' self-reported clinical practices and adherence to national
      immunization guidelines after the introduction of pneumococcal conjugate vaccine.
AB  - BACKGROUND: Little is known about whether pneumococcal conjugate vaccine (PCV)
      has altered pediatricians' practices regarding well-child and acute care.
      OBJECTIVES: To (1) describe whether PCV caused pediatricians to move other
      routine infant vaccines and/or add routine visits; (2) characterize adherence to
      national immunization recommendations; and (3) determine whether PCV altered
      pediatricians' planned clinical approach to well-appearing febrile infants.
      DESIGN AND METHODS: One year after PCV was added to the pediatric immunization
      schedule, we mailed a 23-item survey to 691 randomly selected pediatricians in
      Massachusetts. The adjusted response rate was 77%. RESULTS: After PCV
      introduction, 39% of pediatricians moved other routine infant vaccines to
      different visits and 15% added routine visits to the infant schedule. The self
      reported immunization schedules of 36% were nonadherent to national immunization
      guidelines for at least 1 vaccine. Nonadherence rates were significantly higher
      among pediatricians who had been in practice longer, moved another vaccine
      because of PCV introduction, and/or offered to give shots later when multiple
      injections were due. For a hypothetical febrile 8-month-old girl who had received
      3 doses of PCV, pediatricians reported they were significantly less likely to (1)
      perform both blood and urine testing and (2) prescribe antibiotics than in the
      pre-PCV era. CONCLUSIONS: The introduction of PCV may have had unintended effects
      on pediatric primary care, including decreased adherence to national
      recommendations for the timing of immunizations and decreased urine testing for
      well-appearing febrile infants. Special efforts may be warranted to ensure that
      pediatricians remain current with changing recommendations.

PMID- 15237072
TI  - Sex differences in adolescent exposure to alcohol advertising in magazines.

PMID- 15237073
TI  - Youths' involvement with guns: motivation vs availability.

PMID- 15237074
TI  - Bronchiolitis.

PMID- 15237075
TI  - Immunization injections.

PMID- 15237076
TI  - Moses.

PMID- 15237077
TI  - Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that
      express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate
      cortex in schizophrenia and bipolar disorder.
AB  - BACKGROUND: Disturbances of gamma-aminobutyric acid interneurons in the cerebral
      cortex contribute to the pathophysiology of schizophrenia and bipolar disorder.
      The activity of these neurons is, in turn, modulated by glutamatergic inputs
      furnished by pyramidal neurons. OBJECTIVE: To test the hypothesis that
      glutamatergic inputs onto gamma-aminobutyric acid interneurons via the N-methyl-d
      aspartate (NMDA) receptor are altered in the anterior cingulate cortex in
      schizophrenia and bipolar disorder. DESIGN: A double in situ hybridization
      technique was used to simultaneously label the messenger RNA (mRNA) for the NMDA
      NR(2A) subunit with (35)sulfur and the mRNA for the 67-kDa isoform of the gamma
      aminobutyric acid synthesizing enzyme glutamic acid decarboxylase (GAD(67)) with
      digoxigenin. SETTING: Postmortem human brain studies. PARTICIPANTS: We studied 17
      subjects with schizophrenia, 17 subjects with bipolar disorder, and 17 normal
      control subjects. RESULTS: The density of all GAD(67) mRNA-containing neurons was
      decreased by 53% and 28%, in layers 2 and 5, respectively, in subjects with
      schizophrenia, whereas in subjects with bipolar disorder there was a 35%
      reduction in layer 2 only. For GAD(67) mRNA-containing neurons that co-expressed
      NR(2A)mRNA, their numerical density was decreased by 73% and 52%, in layers 2 and
      5, respectively, in subjects with schizophrenia and by 60% in layer 2 in those
      with bipolar disorder. In the schizophrenia group, the density of the GAD(67)mRNA
      containing neurons that did not co-express NR(2A)mRNA was also decreased by 42%
      in layer 2. In both disease groups, the expression level of NR(2A)mRNA in GAD(67)
      mRNA-containing cells was unaltered. CONCLUSIONS: The density of gamma
      aminobutyric acid interneurons that express the NMDA NR(2A)subunit appears to be
      decreased in schizophrenia and bipolar disorder. Future studies will address
      whether subpopulations of these neurons may be differentially affected in the 2
      conditions.

PMID- 15237078
TI  - Pathways that make voices: white matter changes in auditory hallucinations.
AB  - BACKGROUND: The origin of auditory hallucinations, which are one of the core
      symptoms of schizophrenia, is still a matter of debate. It has been hypothesized
      that alterations in connectivity between frontal and parietotemporal speech
      related areas might contribute to the pathogenesis of auditory hallucinations.
      These networks are assumed to become dysfunctional during the generation and
      monitoring of inner speech. Magnetic resonance diffusion tensor imaging is a
      relatively new in vivo method to investigate the directionality of cortical white
      matter tracts. OBJECTIVE: To investigate, using diffusion tensor imaging, whether
      previously described abnormal activation patterns observed during auditory
      hallucinations relate to changes in structural interconnections between the
      frontal and parietotemporal speech-related areas. METHODS: A 1.5 T magnetic
      resonance scanner was used to acquire twelve 5-mm slices covering the Sylvian
      fissure. Fractional anisotropy was assessed in 13 patients prone to auditory
      hallucinations, in 13 patients without auditory hallucinations, and in 13 healthy
      control subjects. Structural magnetic resonance imaging was conducted in the same
      session. Based on an analysis of variance, areas with significantly different
      fractional anisotropy values between groups were selected for a confirmatory
      region of interest analysis. Additionally, descriptive voxel-based t tests
      between the groups were computed. RESULTS: In patients with hallucinations, we
      found significantly higher white matter directionality in the lateral parts of
      the temporoparietal section of the arcuate fasciculus and in parts of the
      anterior corpus callosum compared with control subjects and patients without
      hallucinations. Comparing patients with hallucinations with patients without
      hallucinations, we found significant differences most pronounced in the left
      hemispheric fiber tracts, including the cingulate bundle. CONCLUSION: Our
      findings suggest that during inner speech, the alterations of white matter fiber
      tracts in patients with frequent hallucinations lead to abnormal coactivation in
      regions related to the acoustical processing of external stimuli. This abnormal
      activation may account for the patients' inability to distinguish self-generated
      thoughts from external stimulation.

PMID- 15237079
TI  - Clinical results for patients with major depressive disorder in the Texas
      Medication Algorithm Project.
AB  - CONTEXT: The Texas Medication Algorithm Project is an evaluation of an algorithm
      based disease management program for the treatment of the self-declared
      persistently and seriously mentally ill in the public mental health sector.
      OBJECTIVE: To present clinical outcomes for patients with major depressive
      disorder (MDD) during 12-month algorithm-guided treatment (ALGO) compared with
      treatment as usual (TAU). DESIGN: Effectiveness, intent-to-treat, prospective
      trial comparing patient outcomes in clinics offering ALGO with matched clinics
      offering TAU. SETTING: Four ALGO clinics, 6 TAU clinics, and 4 clinics that offer
      TAU to patients with MDD but provide ALGO for schizophrenia or bipolar disorder.
      Patients Male and female outpatients with a clinical diagnosis of MDD (psychotic
      or nonpsychotic) were divided into ALGO and TAU groups. The ALGO group included
      patients who required an antidepressant medication change or were starting
      antidepressant therapy. The TAU group initially met the same criteria, but
      because medication changes were made less frequently in the TAU group, patients
      were also recruited if their Brief Psychiatric Rating Scale total score was
      higher than the median for that clinic's routine quarterly evaluation of each
      patient. MAIN OUTCOME MEASURES: Primary outcomes included (1) symptoms measured
      by the 30-item Inventory of Depressive Symptomatology-Clinician-Rated scale (IDS
      C(30)) and (2) function measured by the Mental Health Summary score of the
      Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) obtained every 3
      months. A secondary outcome was the 30-item Inventory of Depressive
      Symptomatology-Self-Report scale (IDS-SR(30)). RESULTS: All patients improved
      during the study (P<.001), but ALGO patients had significantly greater symptom
      reduction on both the IDS-C(30) and IDS-SR(30) compared with TAU. ALGO was also
      associated with significantly greater improvement in the SF-12 mental health
      score (P =.046) than TAU. CONCLUSION: The ALGO intervention package during 1 year
      was superior to TAU for patients with MDD based on clinician-rated and self
      reported symptoms and overall mental functioning.

PMID- 15237080
TI  - Decreased catalytic activity and expression of protein kinase C isozymes in
      teenage suicide victims: a postmortem brain study.
AB  - BACKGROUND: Teenage suicide is a major public health concern. Although there is
      some understanding of the psychosocial factors associated with teenage suicide,
      little is known about the neurobiologic factors of teenage suicide. Protein
      kinase C (PKC) is a critical phosphorylating enzyme in the phosphoinositide
      signaling pathway (which is involved in many physiologic functions in the brain
      and has been implicated in the pathogenesis of mood disorders) and is also a
      target for the therapeutic action of mood-stabilizing drugs. OBJECTIVE: To
      examine whether the pathogenesis of teenage suicide is associated with changes in
      PKC. DESIGN: Postmortem brain study. PARTICIPANTS: Seventeen teenage suicide
      victims and 17 nonpsychiatric control subjects. MAIN OUTCOME MEASURES: Catalytic
      activity of PKC and protein and messenger RNA levels of various PKC isozymes,
      such as PKC alpha, beta, and gamma, were determined in the prefrontal cortex and
      hippocampus of both groups. RESULTS: Protein kinase C activity was statistically
      significantly decreased in membrane and cytosol fractions of the prefrontal
      cortex and hippocampus of teenage suicide victims compared with control subjects.
      Statistically significant decreases in protein levels of PKC alpha, beta I, beta
      II, and gamma isozymes were also observed in both of these fractions. These
      decreases were associated with decreases in levels of their respective messenger
      RNAs. CONCLUSION: Because many physiologic functions are mediated through
      phosphorylation by PKC and because PKC is a target for the therapeutic action of
      psychoactive drugs, our findings indicate that the pathogenesis of teenage
      suicide may be associated with abnormalities in PKC and that PKC may be a target
      for therapeutic intervention in patients with suicidal behavior.

PMID- 15237081
TI  - Increased activation of anterior paralimbic and executive cortex from waking to
      rapid eye movement sleep in depression.
AB  - BACKGROUND: Depression is associated with sleep disturbances, including
      alterations in rapid eye movement (REM) sleep, that may relate to the
      neurobiology of the disorder. Given that REM sleep activates limbic and anterior
      paralimbic cortex and that depressed patients demonstrate increases in
      electroencephalographic sleep measures of REM, we hypothesized greater activation
      of these structures during waking to REM sleep in depressed patients. DESIGN:
      Subjects completed electroencephalographic sleep and regional cerebral glucose
      metabolism assessments during both waking and REM sleep using [(18)F]fluoro-2
      deoxy-D-glucose positron emission tomography. SETTING: Patients and healthy
      subjects recruited from the general community to participate in a research study
      of depression at an academic medical center. Patients Twenty-four unmedicated
      patients who met the Structured Clinical Interview for DSM-IV criteria for
      current major depression and who had a score of 15 or higher on a 17-item
      Hamilton Rating Scale for Depression; 14 medically healthy subjects of comparable
      age and sex who were free of mental disorders. MAIN OUTCOME MEASURES:
      Electroencephalographic sleep, semiquantitative and relative regional cerebral
      metabolism during waking and REM sleep. RESULTS: Depressed patients showed
      greater REM sleep percentages. While both healthy and depressed patients
      activated anterior paralimbic structures from waking to REM sleep, the spatial
      extent of this activation was greater in the depressed patients. Additionally,
      depressed patients showed greater activation in bilateral dorsolateral
      prefrontal, left premotor, primary sensorimotor, and left parietal cortices, as
      well as in the midbrain reticular formation. CONCLUSIONS: Increased anterior
      paralimbic activation from waking to REM sleep may be related to affective
      dysregulation in depressed patients. Increased activation of executive cortex may
      be related to a cognitive dysregulation. These results suggest that altered
      function of limbic/anterior paralimbic and prefrontal circuits in depression is
      accentuated during the REM sleep state. The characteristic sleep disturbances of
      depression may reflect this dysregulation.

PMID- 15237082
TI  - Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients
      with major depression.
AB  - BACKGROUND: Measurement of cortical gamma-aminobutyric acid (GABA) and glutamate
      concentrations is possible using proton magnetic resonance spectroscopy. An
      initial report, using this technique, suggested that occipital cortex GABA
      concentrations are reduced in patients with major depressive disorder (MDD)
      relative to healthy comparison subjects. OBJECTIVES: To replicate the GABA
      findings in a larger sample of MDD patients, to examine the clinical correlates
      of the GABA reductions in these subjects, and to examine other critical
      metabolite levels. DESIGN: Study for association. SETTING: Academic clinical
      research program. PARTICIPANTS: The GABA measurements were made on 38 healthy
      control subjects and 33 depressed subjects. INTERVENTIONS: Occipital cortex
      metabolite levels were measured using proton magnetic resonance spectroscopy.
      MAIN OUTCOME MEASURES: The levels of occipital cortex GABA, glutamate, N
      acetylaspartate, aspartate, creatine, and choline-containing compounds, along
      with several measures of tissue composition, were compared between the 2 groups.
      RESULTS: Depressed subjects had significantly lower occipital cortex GABA
      concentrations compared with healthy controls (P =.01). In addition, mean
      glutamate levels were significantly increased in depressed subjects compared with
      healthy controls (P<.001). Significant reductions in the percentage of solid
      tissue (P =.009) and the percentage of white matter (P =.04) in the voxel were
      also observed. An examination of a combined database including subjects from the
      original study suggests that GABA and glutamate concentrations differ among MDD
      subtypes. CONCLUSIONS: The study replicates the findings of decreased GABA
      concentrations in the occipital cortex of subjects with MDD. It also demonstrates
      that there is a change in the ratio of excitatory-inhibitory neurotransmitter
      levels in the cortex of depressed subjects that may be related to altered brain
      function. Last, the combined data set suggests that magnetic resonance
      spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.

PMID- 15237083
TI  - Combined pharmacotherapy and psychological treatment for depression: a systematic
      review.
AB  - BACKGROUND: Adherence to antidepressant medication use is a problem in clinical
      practice. Some authors have posited that combined psychological treatment
      facilitates adherence to pharmacotherapy. OBJECTIVES: To study the relationship
      between adherence to use of and efficacy of antidepressant drugs plus
      psychological treatment vs drug treatment alone in depressive disorders. DATA
      SOURCES: MEDLINE, Current Contents, PsychInfo, Cochrane Library, and reference
      lists were searched, from January 1980 to November 2002. STUDY SELECTION:
      Randomized clinical trials comparing antidepressant treatment alone with
      antidepressant treatment in combination with a psychological intervention in
      depressive disorders were considered. The decision to include studies in the meta
      analysis was performed by 2 reviewers. DATA EXTRACTION: Three independent
      reviewers extracted the data, using a precoded form. Methodological quality of
      the studies was evaluated in terms of allocation concealment and independence of
      evaluators. DATA SYNTHESIS: Sixteen trials met the inclusion criteria, with 932
      patients randomized to pharmacotherapy alone and 910 to combined treatment.
      Overall, patients receiving combined treatment improved significantly compared
      with those receiving drug treatment alone (odds ratio [OR], 1.86; 95% confidence
      interval [CI], 1.38-2.52), but dropouts and nonresponders did not differ in
      distribution between the 2 treatment modalities (OR, 0.86; 95% CI, 0.60-1.24).
      Studies longer than 12 weeks showed a significant advantage of combined treatment
      over drug treatment alone (OR, 2.21; 95% CI, 1.22-4.03), with a significant
      reduction in dropouts compared with nonresponders (OR, 0.59; 95% CI, 0.39-0.88).
      These estimates were not affected by study quality. CONCLUSIONS: Psychological
      treatment combined with antidepressant therapy is associated with a higher
      improvement rate than drug treatment alone. In longer therapies, the addition of
      psychotherapy helps to keep patients in treatment. Further studies are needed to
      investigate whether the improvement in response attributable to the combination
      of drug treatment and psychotherapy can be achieved by a combination of
      pharmacotherapy and a compliance-enhancing intervention.

PMID- 15237084
TI  - Mapping structural brain alterations in obsessive-compulsive disorder.
AB  - BACKGROUND: Recent technical developments have made it feasible to
      comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To
      describe the structural brain alterations detected in the magnetic resonance
      images of a large series of patients with obsessive-compulsive disorder (OCD)
      using imaging procedures that allow the evaluation of volume changes throughout
      the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary
      hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72
      age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences
      were obtained in all participants. A statistical parametric mapping approach was
      used to delineate possible anatomical alterations in the entire brain. To
      preserve volumetric information, voxel values were modulated by the Jacobian
      determinants (volume change measurement) derived from spatial normalization. MAIN
      OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with
      OCD showed reduced gray matter volume in the medial frontal gyrus, the medial
      orbitofrontal cortex, and the left insulo-opercular region. A relative increase
      in gray matter volume was observed bilaterally in the ventral part of the putamen
      and in the anterior cerebellum. All these brain alterations were abnormally
      correlated in patients with OCD, and age statistically significantly contributed
      to the relative enlargement observed in the striatal areas. Disease severity, the
      nature of symptoms, and comorbidities were not related to the changes described.
      Nevertheless, patients with prominent aggressive obsessions and checking
      compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS:
      The pattern of anatomical features depicted by this voxelwise approach is
      consistent with data from functional studies. The reported anatomical maps
      identified the specific parts of the frontostriatal system that were altered in
      patients with OCD and detected changes in anatomically connected distant regions.
      These data further define the structural brain alterations in OCD and may
      contribute to constraining the prevailing biological models of this psychiatric
      process.

PMID- 15237085
TI  - ADHD as a risk factor for incident unprovoked seizures and epilepsy in children.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) occurs more
      frequently than expected in prevalent cohorts with epilepsy. The association has
      been attributed to the epilepsy or its treatment, although it is impossible to
      determine in previous studies which condition occurs first. OBJECTIVES: To
      conduct a population-based case-control study of all newly diagnosed unprovoked
      seizures among Icelandic children younger than 16 years to address the question
      of time order. DESIGN: Children with seizures were matched to the next 2 same-sex
      births from the population registry. The Diagnostic Interview Schedule for
      Children was used to make a DSM-IV diagnosis of ADHD in a standardized fashion
      among cases and controls aged 3 to 16 years. RESULTS: A history of ADHD was 2.5
      fold more common among children with newly diagnosed seizures than among control
      subjects (95% confidence interval [CI], 1.1-5.5). The association was restricted
      to ADHD predominantly inattentive type (odds ratio [OR], 3.7; 95% CI, 1.1-12.8),
      not ADHD predominantly hyperactive-impulsive type (OR, 1.8; 95% CI, 0.6-5.7) or
      ADHD combined type (OR, 2.5; 95% CI, 0.3-18.3). Seizure type, etiology, sex, or
      seizure frequency at diagnosis (1 or >1) did not affect findings. CONCLUSION:
      Attention-deficit/hyperactivity disorder occurs more often than expected before
      unprovoked seizures, suggesting a common antecedent for both conditions.

PMID- 15237086
TI  - Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder.
AB  - BACKGROUND: Very little is known about how different sets of risk factors
      interact to influence risk for psychiatric disorder. OBJECTIVE: To replicate a
      recent report of a genotype-environment interaction that predicts risk for
      antisocial behavior in boys. DESIGN: Characterizing risk for conduct disorder in
      boys in association with monoamine oxidase A genotype and exposure to familial
      adversity, defined by interparental violence, parental neglect, and inconsistent
      discipline. SETTING: A community-based sample of twin boys. PARTICIPANTS: Five
      hundred fourteen male twins aged 8 to 17 years. MAIN OUTCOME MEASURE: Conduct
      disorder. RESULTS: There was a main effect of adversity but not of monoamine
      oxidase A on risk for conduct disorder. Low monoamine oxidase A activity
      increased risk for conduct disorder only in the presence of an adverse childhood
      environment. Neither a passive nor an evocative genotype-environment correlation
      accounted for the interaction. CONCLUSION: This study replicates a recent report
      of a genotype-environment interaction that predicts individual variation in risk
      for antisocial behavior in boys.

PMID- 15237087
TI  - Results of the first round of a demonstration pilot of screening for colorectal
      cancer in the United Kingdom.
AB  - OBJECTIVE: To assess the feasibility of introducing into the UK's NHS a national
      screening programme for colorectal cancer based on faecal occult blood testing.
      DESIGN: Demonstration pilot. SETTING: Two English health authorities and three
      Scottish health boards. PARTICIPANTS: People aged 50-69 years. RESULTS: 478,250
      residents of the pilot areas were invited to take part in the screening
      programme. Uptake (the proportion in whom a final faecal occult blood test result
      was available) was 56.8% (n = 271,646). The overall rate of a positive test
      result was 1.9% and the rate for detecting cancer was 1.62 per 1000 people
      screened. Both these values were higher in Scotland than in England, higher in
      men than in women, and increased with age. The positive predictive value was
      10.9% for cancer and 35.0% for adenoma. 552 cancers were detected by screening;
      92 (16.6%) were polyp cancers. 48% of all screen detected cancers were Dukes's
      stage A, and 1% had metastasised at the time of diagnosis. CONCLUSIONS: Screening
      for colorectal cancer by testing for faecal occult blood is feasible within the
      context of the United Kingdom's NHS. Screening should lead to a reduction in
      deaths from colorectal cancer in the population offered screening.

PMID- 15237088
TI  - Does access to cardiac investigation and treatment contribute to social and
      ethnic differences in coronary heart disease? Whitehall II prospective cohort
      study.
AB  - OBJECTIVE: To determine whether access to cardiac procedures and drugs
      contributes to social and ethnic differences in coronary heart disease in a
      population setting. DESIGN: Prospective study with follow up over 15 years. Civil
      service employment grade was used as a measure of individual socioeconomic
      position. Need for cardiac care was determined by the presence of angina,
      myocardial infarction, and coronary risk factors. SETTING: 20 civil service
      departments originally located in London. PARTICIPANTS: 10,308 civil servants
      (3414 women; 560 South Asian) aged 35-55 years at baseline in 1985-8. MAIN
      OUTCOME MEASURES: Use of exercise electrocardiography, coronary angiography, and
      coronary revascularisation procedures and secondary prevention drugs. RESULTS:
      Inverse social gradients existed in incident coronary morbidity and mortality.
      South Asian participants also had higher rates than white participants. After
      adjustment for clinical need, social position showed no association with the use
      of cardiac procedures or secondary prevention drugs. For example, men in the low
      versus high employment grade had an age adjusted odds ratio for angiography of
      1.87 (95% confidence interval 1.32 to 2.64), which decreased to 1.27 (0.83 to
      1.94) on adjustment for clinical need. South Asians tended to be more likely to
      have cardiac procedures and to be taking more secondary prevention drugs than
      white participants, even after adjustment for clinical need. CONCLUSION: This
      population based study, which shows the widely observed social and ethnic
      patterning of coronary heart disease, found no evidence that low social position
      or South Asian ethnicity was associated with lower use of cardiac procedures or
      drugs, independently of clinical need. Differences in medical care are unlikely
      to contribute to social or ethnic differences in coronary heart disease in this
      cohort.

PMID- 15237089
TI  - Myeloperoxidase and plaque vulnerability.

PMID- 15237090
TI  - Origin of neointimal cells in autologous vein graft.

PMID- 15237091
TI  - Vitamin E is not deficient in human atherosclerotic plaques.

PMID- 15237093
TI  - Inhibition of Na+-H+ exchange by cariporide reduces inflammation and heart
      failure in rabbits with myocardial infarction.
AB  - The aim of this study was to assess the effects of the Na+-H+ exchange inhibitor
      cariporide on left ventricular (LV) morphology and function as well as
      inflammation in rabbits with heart failure. Rabbits with myocardial infarction
      (MI) and sham controls were randomized to receive either standard chow or chow
      supplemented with cariporide for 9 weeks. LV morphology was determined by
      echocardiography. LV systolic and diastolic function was assessed under load
      dependent and -independent conditions by analysis of LV pressure-volume loops
      using piezo-electric crystals. Plasma concentrations of C-reactive protein and
      aldosterone were measured. Rabbits with MI developed LV dilatation that was
      reduced by cariporide. Systolic and diastolic LV function was impaired in rabbits
      with MI when compared to sham, as indicated by a decreased dP/dtmax (MI: 3537 +/-
      718 mmHg s(-1), sham: 5839 +/- 247 mmHg s(-1), P < 0.05), the load-independent
      preload recruitable stroke work (PRSW)(MI: 22 +/-7 mmHg, sham: 81 +/- 23 mmHg, P
      < 0.05) and a reduction in the time constant of relaxation tau (tau) (MI: 27+/-1
      ms, sham: 17+/-1 ms, P < 0.05), and significantly improved by cariporide
      (dP/dtmax: 4586 +/- 374 mmHg s(-1), PRSW: 67 +/- 18 mmHg, tau: 20 +/- 2 ms; P <
      0.05 vs MI/control). Induction of MI was associated with an increase in
      aldosterone and CRP, indicating activation of the neurohormonal and the
      inflammatory system that were largely reduced by cariporide. Cariporide improves
      LV morphology and function post MI and suppresses inflammation and neurohormonal
      activation in congestive heart failure (CHF). Na+-H+ exchange inhibition may
      represent a new pharmaceutical approach for the treatment of CHF.

PMID- 15237094
TI  - KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea:
      the role of the epithelium, cyclic nucleotides and K+ channels.
AB  - 7-[2-[4-(2-chlorophenyl)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) produces
      tracheal relaxation, intracellular accumulation of cyclic nucleotides, inhibition
      of phosphodiesterases (PDEs) and activation of K+ channels. KMUP-1 (0.01-100
      microm) induced concentration-dependent relaxation responses in guinea-pig
      epithelium-intact trachea precontracted with carbachol. Relaxation responses were
      also elicited by the PDE inhibitors theophylline, 3-isobutyl-1-methylxanthine
      (IBMX), milrinone, rolipram and zaprinast (100 microm), and a KATP channel
      opener, levcromakalim. Tracheal relaxation induced by KMUP-1 was attenuated by
      epithelium removal and by pretreatment with inhibitors of soluble guanylate
      cyclase (sGC) (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 1 microm),
      nitric oxide synthase (Nomega-nitro-L-arginine methyl ester, 100 microm), K+
      channels (tetraethylammonium, 10 mm), KATP channels (glibenclamide, 1 microm),
      voltage-dependent K+ channels (4-aminopyridine, 100 microm) and Ca2+-dependent K+
      channels (charybdotoxin, 0.1 microm or apamin, 1 microm). Both KMUP-1 (10 microm)
      and theophylline nonselectively and slightly inhibited the enzyme activity of
      PDE3, 4 and 5, suggesting that they are able to inhibit the metabolism of
      adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic
      monophosphate (cyclic GMP). Likewise, the effects of IBMX were also measured and
      its IC50 values for PDE3, 4 and 5 were 6.5 +/- 1.2, 26.3 +/- 3.9 and 31.7 +/- 5.3
      microm, respectively. KMUP-1 (0.01-10 microm) augmented intracellular cyclic AMP
      and cyclic GMP levels in guinea-pig cultured tracheal smooth muscle cells. These
      increases in cyclic AMP and cyclic GMP were abolished in the presence of an
      adenylate cyclase inhibitor SQ 22536 (100 microm) and an sGC inhibitor ODQ (10
      microm), respectively. KMUP-1 (10 microm) increased the expression of protein
      kinase A (PKARI) and protein kinase G (PKG1alpha1beta) in a time-dependent
      manner, but this was only significant for PKG after 9 h. Intratracheal
      administration of tumour necrosis factor-alpha (TNF-alpha, 0.01 mg kg(-1))
      induced bronchoconstriction and exhibited a time-dependent increase in lung
      resistance (RL) and decrease in dynamic lung compliance (Cdyn). KMUP-1 (1.0 mg
      kg(-1)), injected intravenously for 10 min before the intratracheal TNF-alpha,
      reversed these changes in RL and Cdyn. These data indicate that KMUP-1 activates
      sGC, produces relaxation that was partly dependent on an intact epithelium,
      inhibits PDEs and increases intracellular cyclic AMP and cyclic GMP, which then
      increases PKA and PKG, leading to the opening of K+ channels and resulting
      tracheal relaxation.

PMID- 15237095
TI  - Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral
      arteries.
AB  - This study examines the importance of mitogen-activated protein kinases (MAPKs)
      in upregulation of endothelin type B (ETB) receptors. Rat middle cerebral
      arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel
      segments were mounted in myographs and the contractile responses to endothelin-1
      (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor
      agonist) were studied. We used real-time PCR to measure the receptor mRNA levels.
      An ELISA assay showed the activation of ERK1/2 kinases after 3 h.
      Immunohistochemistry revealed the presence of ETB receptors on the vessels. After
      organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK
      inhibitors U0126 and SB386023 diminished the contractile response to S6c. The p38
      MAPK inhibitor SB239063 did not affect the S6c-induced contraction. The ET-1
      induced vasoconstriction was increased after incubation with SB386023 or
      SB239063, while unaffected by U0126. The ETB receptor mRNA levels were diminished
      by SB386023 and U0126. The ETA receptor mRNA levels were unaffected. The levels
      of activated ERK1/2 kinases were significantly higher after 3 h of organ culture
      as compared to fresh vessels. The level of ETB receptor protein on the smooth
      muscle cells of the MCA, visualised by immunohistochemistry, was somewhat
      diminished by SB386023. Our results show that the ERK1/2 MAPK is important in the
      upregulation of contractile ETB receptors in MCA after organ culture. Since there
      is a similar upregulation in models of focal ischaemia and subarachnoid
      haemorrhage, this may be an important pathophysiological event.

PMID- 15237096
TI  - Calcitonin gene-related peptide (CGRP) antagonists: blockers of neuronal
      transmission in migraine.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator
      that is contained in and released from sensory nerves. CGRP has been implicated
      in migraine, and the nonpeptide CGRP antagonist BIBN4096BS has been shown to be
      effective in clinical trials in migraine. To date, it has been largely assumed
      that the CGRP antagonist is effective due to its ability to block vasodilator
      activity. Goadsby and co-workers present data that now suggest that CGRP
      antagonists may also block neuronal transmission in migraine.

PMID- 15237098
TI  - Requirement for flow in the blockade of endothelium-derived hyperpolarizing
      factor (EDHF) by ascorbate in the bovine ciliary artery.
AB  - We previously reported that ascorbate inhibits endothelium-derived
      hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine perfused
      ciliary circulation and rat perfused mesentery, but not in rings of bovine or
      porcine coronary artery. In this study, we have compared the ability of ascorbate
      to inhibit EDHF-mediated vasodilatation in a single vessel, the bovine long
      posterior ciliary artery, when perfused and when mounted as rings in a myograph.
      Both in segments perfused at a flow rate of 2.5 ml min(-1) and in rings mounted
      in a myograph, bradykinin and acetylcholine each induced vasodilator responses
      that were mediated jointly by EDHF and nitric oxide, as revealed by their
      respective blocking agents, apamin/charybdotoxin, and L-NAME. Ascorbate (50 and
      150 microm) induced a time (max at 2-3 h)-dependent inhibition of the EDHF
      mediated component of vasodilatation to bradykinin or acetylcholine in perfused
      segments, but not in rings. Ascorbate (50 microm) failed to inhibit bradykinin
      induced vasodilatation at a flow rate of 1.25 ml min(-1) or below, but produced
      graded blockade at the higher flow rates of 2.5 and 5 ml min(-1). Furthermore,
      using a pressure myograph where pressure and flow were independently controlled,
      it was confirmed that the inhibitory action of ascorbate (150 microm) was
      directly related to flow per se and not any associated changes in pressure. Thus,
      we have shown in the bovine ciliary artery that ascorbate inhibits EDHF-mediated
      vasodilatation under conditions of flow but not in a static myograph. The
      mechanism by which flow renders EDHF susceptible to inhibition by ascorbate
      remains to be determined.

PMID- 15237097
TI  - Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular
      transmission in the cat.
AB  - Calcitonin gene-related peptide (CGRP) is released into the cranial circulation
      of humans during acute migraine. To determine whether CGRP is involved in
      neurotransmission in craniovascular nociceptive pathways, we microiontophoresed
      onto neurons in the trigeminocervical complex and intravenously administered the
      CGRP receptor antagonists alpha-CGRP-(8-37) and BIBN4096BS. Cats were
      anaesthetised with alpha-chloralose, and using halothane during surgical
      preparation. A craniotomy and C1/C2 laminectomy allowed access to the superior
      sagittal sinus (SSS) and recording site. Recordings of activity in the
      trigeminocervical complex evoked by electrical stimulation of the SSS were made.
      Multibarrelled micropipettes incorporating a recording electrode were used for
      microiontophoresis of test substances. Cells recorded received wide dynamic range
      (WDR) or nociceptive specific (NS) input from cutaneous receptive fields on the
      face or forepaws. Cell firing was increased to 25-30 Hz by microiontophoresis of
      L-glutamate (n = 43 cells). Microiontophoresis of alpha-CGRP excited seven of 17
      tested neurons. BIBN4096BS inhibited the majority of units (26 of 38 cells)
      activated by l-glutamate, demonstrating a non-presynaptic site of action for
      CGRP. alpha-CGRP-(8-37) inhibited a similar proportion of units (five of nine
      cells). Intravenous BIBN4096BS resulted in a dose-dependent inhibition of
      trigeminocervical SSS-evoked activity (ED50 31 microg kg(-1)). The maximal effect
      observed within 30 min of administration. The data suggest that there are non
      presynaptic CGRP receptors in the trigeminocervical complex that can be inhibited
      by CGRP receptor blockade and that a CGRP receptor antagonist would be effective
      in the acute treatment of migraine and cluster headache.

PMID- 15237099
TI  - The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS blocks
      CGRP and adrenomedullin vasoactive responses in the microvasculature.
AB  - Calcitonin gene-related peptide (CGRP) is a potent microvascular dilator
      neuropeptide that is considered to play an essential role in neurogenic
      vasodilatation and in maintaining functional integrity in peripheral tissues. We
      have examined the effect of the nonpeptide CGRP antagonist BIBN4096BS on
      responses to CGRP and the structurally related peptide adrenomedullin, AM, in
      murine isolated aorta and mesentery preparations, and in the cutaneous
      microvasculature in vivo. We show for the first time that BIBN4096BS is an
      effective antagonist of CGRP and AM responses in the murine mesenteric and
      cutaneous microvasculature, and of CGRP in the murine aorta. After local
      administration, BIBN4096BS selectively inhibits the potentiation of microvascular
      permeability in the cutaneous microvasculature by CGRP and AM, with no effect on
      responses induced by other microvascular vasodilators. BIBN4096BS reversed both
      newly developed and established vasoactive responses induced by CGRP. The ability
      of CGRP to potentiate plasma extravasation was lost when coinjected with compound
      48/80 (where mast cells would be activated to release proteases), but regained
      when soybean trypsin inhibitor was coinjected with compound 48/80. These results
      demonstrate that BIBN4096BS is a selective antagonist of responses induced by
      CGRP and AM in the mouse microvasculature, and CGRP in the mouse aorta. The
      ability of BIBN4096BS to block an established CGRP microvascular vasodilatation
      indicates that the sustained vasodilator activity of CGRP is due to the retention
      of the active intact peptide and the continued involvement of the CGRP receptor.

PMID- 15237100
TI  - Pharmacological prevention of cardiovascular aging--targeting the Maillard
      reaction.
AB  - The development of myocardial and large vessel stiffness with aging underlies the
      development of diastolic heart failure and isolated systolic hypertension.
      Nonenzymatic reaction between glucose and proteins (Maillard reaction) leading to
      collagen crosslinking in the myocardium and arterial wall has been implicated in
      age-related increase in cardiovascular stiffness. In the present issue, Chang et
      al. show that aminoguanidine, an inhibitor of protein crosslinking, retards age
      related decline in the elastic properties of the left ventricle and arteries. The
      significance of these findings is discussed in this commentary.

PMID- 15237101
TI  - Expression and functional activity of PPARgamma in pancreatic beta cells.
AB  - Rosiglitazone is an agonist of peroxisome proliferator activated receptor-gamma
      (PPARgamma) and ameliorates insulin resistance in type II diabetes. In addition,
      it may also promote increased pancreatic beta-cell viability, although it is not
      known whether this effect is mediated by a direct action on the beta cell. We
      have investigated this possibility. Semiquantitative real-time reverse
      transcription-polymerase chain reaction analysis (Taqman) revealed that freshly
      isolated rat islets and the clonal beta-cell line, BRIN-BD11, express PPARgamma,
      as well as PPARalpha and PPARdelta. The levels of expression of PPARgamma were
      estimated by reference to adipose tissue and were found to represent
      approximately 60% (islets) and 30% (BRIN-BD11) of that found in freshly isolated
      visceral adipose tissue. Western blotting confirmed the presence of
      immunoreactive PPARgamma in rat (and human) islets and in BRIN-BD11 cells.
      Transfection of BRIN-BD11 cells with a PPARgamma-sensitive luciferase reporter
      construct was used to evaluate the functional competence of the endogenous
      PPARgamma. Luciferase activity was modestly increased by the putative endogenous
      ligand, 15-deoxy-Delta12,14 prostaglandin J2 (15dPGJ2). Rosiglitazone also caused
      activation of the luciferase reporter construct but this effect required
      concentrations of the drug (50-100 microm) that are beyond the expected
      therapeutic range. This suggests that PPARgamma is relatively insensitive to
      activation by rosiglitazone in BRIN-BD11 cells. Exposure of BRIN-BD11 cells to
      the lipotoxic effector, palmitate, caused a marked loss of viability. This was
      attenuated by treatment of the cells with either actinomycin D or cycloheximide
      suggesting that a pathway of programmed cell death was involved. Rosiglitazone
      failed to protect BRIN-BD11 cells from the toxic actions of palmitate at
      concentrations up to 50 microm. Similar results were obtained with a range of
      other PPARgamma agonists. Taken together, the present data suggest that, at least
      under in vitro conditions, thiazolidinediones do not exert direct protective
      effects against fatty acid-mediated cytotoxicity in pancreatic beta cells.

PMID- 15237102
TI  - Effects of dietary lectins on ion transport in epithelia.
AB  - Phytohemagglutinins are widely distributed in common food items. They constitute
      a heterogeneous group of proteins, which are often resistant to proteolysis in
      the gastrointestinal tract. Upon binding to the luminal membrane of intestinal
      cells, they can interfere with digestive, protective or secretory functions of
      the intestine. Phytohemagglutinins present in red kidney beans and jackbeans have
      been shown to induce diarrhea and hypersecretion in human airways, but the
      underlying mechanisms remain obscure. We examined how agglutinins from wheat germ
      (WGA), soy bean (SBA), red kidney beans (Pha-E, Pha-L), and jackbeans (Con-A)
      affect ion transport in mouse airways and large intestine using Ussing chamber
      techniques. We found that Pha-E, Pha-L, and Con-A but not WGA and SBA inhibit
      electrogenic Na(+) absorption dose dependently in both colon and trachea. The
      inhibitory effects of Con-A on Na(+) absorption were suppressed by the sugar
      mannose, by inhibition of phospholipase C (PLC) and protein kinase C (PKC). Thus,
      nutritional phytohemagglutinins block salt absorption in a PLC- and PKC-dependent
      manner, probably by inhibition of the epithelial Na(+) channel (ENaC). This
      effect may be therapeutically useful in patients suffering from cystic fibrosis.

PMID- 15237103
TI  - Two cysteines in plant R2R3 MYB domains participate in REDOX-dependent DNA
      binding.
AB  - Plant R2R3 MYB domain proteins comprise one of the largest known families of
      transcription factors. Discrete evolutionary steps have shaped the plant-specific
      R2R3 MYB family from the broadly distributed R1R2R3 MYB proteins. R1R2R3 MYB
      domains have a single Cys residue (Cys-130) that needs to be reduced for DNA
      binding and transcriptional activity. In contrast, most R2R3 MYB domains contain
      two cysteines, Cys-49 and Cys-53, with Cys-53 at the equivalent position as Cys
      130 in R1R2R3 MYB. Using the maize P1 regulator of flavonoid biosynthesis as a
      typical R2R3 MYB-domain protein, we investigated here the in vitro REDOX
      requirement for DNA binding by P1. We show that the C53S mutation requires
      reducing conditions for DNA-binding, whereas C53A binds DNA under oxidizing and
      reducing conditions. Neither mutation impairs the in vivo regulatory activity of
      P1. The C49S and C49A mutants bind DNA in vitro irrespective of the REDOX
      conditions. A C49I mutant, which simulates the MYB domain of c-MYB, binds DNA
      only under reducing conditions, and its binding is significantly affected by the
      C53S replacement. It is interesting that under non-reducing conditions, Cys-49
      and Cys-53 form a disulfide bond that prevents the R2R3 MYB domain from binding
      DNA. Together, our results suggest that the evolutionary origin of Cys-49 within
      the plants has provided R2R3 MYB domains with a regulatory feature not present in
      animal MYB domains, highlighting fundamental structural and functional
      differences between similar DNA-binding domains from plants and animals.

PMID- 15237104
TI  - Domains formed within the N-terminal region of the quorum-sensing activator TraR
      are required for transcriptional activation and direct interaction with RpoA from
      agrobacterium.
AB  - TraR, a quorum-sensing activator, induces transcription from its binding site,
      the tra-box, located upstream of Ti plasmid target promoters. TraR activated
      expression of a lacZ reporter in Escherichia coli only when RpoAAt from
      Agrobacterium tumefaciens was co-expressed. As assessed by gel retardation assays
      RpoAAt, but not RpoAEc, formed a ternary complex with TraR and a tra-box probe in
      vitro. TraR formed similar ternary complexes with alphaCTDAt but not with NTDAt,
      the C- and N-terminal segments of RpoAAt. As measured by surface plasmon
      resonance refractometry, TraR interacted directly with RpoAAt with an affinity
      about five times greater than that observed for its interaction with RpoAEc. The
      activator interacted with alphaCTDAt with kinetics and affinities similar to
      those of the full-sized -subunit. Positive control (PC) mutations at Asp-10 and
      Gly-123 of TraR did not affect DNA binding but greatly decreased the TraR-RpoAAt
      interaction. These two residues combine to form two patches on the activator, one
      of which may be involved in interaction with RpoA. When co-expressed, mutants of
      TraR with substitutions at Asp-10 complementing mutants with substitutions at Gly
      123 for gene activation in an allele-specific manner. Co-expression studies with
      TraR and its PC mutants, and also with complementary PC alleles of TraR, coupled
      with three-dimensional structure are consistent with a hypothesis that both Asp
      10/Gly-123 patches are required for activator function.

PMID- 15237105
TI  - Involvement of IL-17 in Fas ligand-induced inflammation.
AB  - Fas ligand (FasL) has been well characterized as a death factor. However, recent
      studies revealed that ectopic expression of FasL induces inflammation associated
      with massive neutrophil infiltration. We previously demonstrated that the
      neutrophil infiltration-inducing activity of FasL is partly dependent on, but
      partly independent of, IL-1beta. Here we investigated the cytokine profile of
      peritoneal lavage fluid obtained from mice that received i.p. injections of FFL,
      a FasL-expressing tumor cell line. We found that FFL injection caused a marked
      increase of not only IL-1beta but also IL-6, IL-17, IL-18, KC/chemokine CXC
      ligand 1 and macrophage inflammatory protein (MIP)-2, but not of IL-1alpha, IFN
      gamma, TGF-beta or TNF-alpha. The FFL-induced cytokine production was not
      observed in Fas-deficient lpr mice. Among cells transfected to express
      individually IL-1beta, IL-6, IL-17, or IL-18, only those expressing IL-1beta and
      IL-17 induced neutrophil infiltration. In these analyses, as little as 20 pg of
      peritoneal IL-17 induced neutrophil infiltration. The peritoneal IL-17 levels
      after FFL-injection were greatly diminished in IL-1-deficient mice. However, the
      IL-17 level was still above the threshold for neutrophil infiltration. Consistent
      with this, co-administration of the anti-IL-17 antibody with FFL diminished the
      peritoneal KC levels and neutrophil infiltration in IL-1-deficient mice. In
      addition, the expression of IL-17 by the tumor cells inhibited tumor growth in
      wild-type and nude mice. These results indicate that FasL is an upstream
      inflammatory factor that induces a variety of other inflammatory cytokines in
      vivo, and suggest that IL-17 is involved in FasL-induced inflammation in the
      absence of IL-1beta.

PMID- 15237106
TI  - A novel reticular stromal structure in lymph node cortex: an immuno-platform for
      interactions among dendritic cells, T cells and B cells.
AB  - For efficient adaptive immunity, the lymph nodes (LNs) are equipped with a
      strategically organized microarchitecture, which is largely supported by the
      reticular network (RN). The RN can be clearly visualized by fluorescence
      immunohistochemistry coupled with confocal imaging using a monoclonal antibody,
      ER-TR7, and can be subdivided into four structurally distinct regions, each of
      which correlates well with the location of distinct immune cell subsets. In
      addition, we noticed a characteristic reticular structure designated the
      'cortical ridge' at the boundary of the T and B zone, in which dendritic cells
      are preferentially accumulated. In vitro adhesion assays of frozen sections
      demonstrated a preference of dendritic cells for the cortical ridge rather than
      the deeper cortex. Adoptive transfer experiments also demonstrated that antigen
      bearing dendritic cells migrated to this region from peripheral tissues,
      especially in the vicinity of the high endothelial venules, and were anchored on
      the reticular fibers waiting to interact with the antigen-specific T cells. Taken
      together, the findings obtained in this study provide new insights into how the
      LN stromal reticulum works as a specialized 'immuno-platform' for tissue
      compartmentalization and the immune response.

PMID- 15237107
TI  - Antiarthritic effect of VIP in relation to the host resistance against Candida
      albicans infection.
AB  - Vasoactive intestinal peptide (VIP) is one of the prospective candidates for
      clinical application in rheumatoid arthritis (RA). Its antiarthritic effect is
      associated with the suppression of inflammatory and autoimmune responses. The
      ability of VIP to trigger a shift towards Th2 immunity suggests that anti
      infectious host resistance might be affected. In the present study VIP was
      applied at the initiation and at the established phase of collagen-induced
      arthritis (CIA). Mice developed Th2 dominant anti-collagen response. The
      susceptibility to primary and secondary Candida albicans infection was determined
      after VIP administration at the established CIA. The percentage of survivors,
      kidney colonization, cytokine secretion by splenocytes and specific antibody
      synthesis were assessed. Reduced TNF-alpha production but not IFN-gamma and IL-10
      was observed after the first challenge with the pathogen in CIA mice treated with
      VIP while the percentage of survivors was not significantly changed. The adaptive
      immune response was impaired in VIP-treated mice as they were more susceptible to
      reinfection, showed increased kidney colonization and suppressed anti-Candida IgG
      antibody production.

PMID- 15237108
TI  - BASH-deficient mice: limited primary repertoire and antibody formation, but
      sufficient affinity maturation and memory B cell generation, in anti-NP response.
AB  - Signaling through the B cell antigen receptor (BCR) induces activation and
      proliferation of B cells, a response that requires the adaptor protein BASH (also
      known as BLNK/SLP-65). Although BASH and other molecules, such as Btk, PLCgamma2
      and PKCbeta, are known to be essential for T cell-independent immune responses in
      vivo, their requirement during T cell-dependent immune responses, especially
      their role in antibody affinity-maturation and memory B cell generation remains
      unclear. In this study, we examined primary and memory immune responses to the T
      cell-dependent hapten antigen, (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to
      chicken gammaglobulin (CGG), in BASH-deficient mice on a C57BL/6 background. In
      the primary response, NP-specific IgM was barely produced and the typical anti-NP
      IgG1/lambda production was markedly attenuated, but kappa chain was unexpectedly
      over-represented in the anti-NP antibodies. In contrast, CGG-specific IgG1 was
      normally produced. In the memory response, IgG1/lambda antibody with high
      affinity to NP was produced at normal level in the mutant mice. The frequency and
      distribution of somatic mutations in the V(H)186.2 genes of the anti-NP
      IgG1/lambda antibody were also normal. These results indicate that BASH-mediated
      BCR signaling is dispensable for somatic hypermutation and affinity selection, as
      well as generation and response of memory B cells. Interestingly, mutated V(H)
      genes with the same clonal origin were prominent in the anti-NP antibodies of
      BASH-deficient mice, indicating that a limited number of original clones had been
      recruited into the memory compartment. Thus, the scarcity of specific clones in
      the primary repertoire and an impaired primary response is not detrimental to the
      quality and quantity of a memory response.

PMID- 15237109
TI  - Suppression of expression and function of negative immune regulator PD-1 by
      certain pattern recognition and cytokine receptor signals associated with immune
      system danger.
AB  - Stimulation of certain cytokine and pattern recognition receptors enhances
      adaptive immune responses, and in chronic situations, may play a role in the loss
      of self-tolerance. We hypothesized that in addition to upregulating positive
      immune receptors (i.e. co-stimulatory molecules), certain cytokine and pattern
      recognition signals might downregulate negative immune receptors, removing a
      potential barrier to lymphocyte responsiveness. The newly identified CD28 family
      member Programmed Death-1 (PD-1) is an inhibitory receptor involved in peripheral
      tolerance, as evidenced by the frank autoimmunity and autoantibody formation
      found in PD-1-deficient mice. Here we report that antigen-receptor induced PD-1
      expression on murine B cells is markedly reduced by certain signals associated
      with immune system danger, including LPS, CpG oligodeoxynucleotides and several
      pro-inflammatory cytokines, through distinct signaling pathways. We further
      report for the first time that engagement of PD-1 inhibits cell cycle progression
      in primary B cells and that modulation of PD-1 expression by CpG or IL-4
      significantly reverses such inhibition. Our data suggest a novel mechanism for
      enhancement of normal immune responses and disruption of normal tolerance
      mechanisms.

PMID- 15237111
TI  - Acquisition of anergic and suppressive activities in transforming growth factor
      beta-costimulated CD4+CD25- T cells.
AB  - Regulatory T (Tr) cells have been shown to arise in the periphery during
      induction of peripheral tolerance. However, the mechanism involved remains
      elusive. In the present study, we investigated the potential role of transforming
      growth factor (TGF)-beta in the peripheral induction of regulatory phenotypes in
      the conventional CD4(+)CD25(-) T cells. Upon priming in the presence of TGF-beta,
      there was greatly enhanced expression of CD25, cytotoxic T lymphocyte-associated
      antigen 4 (CTLA-4), and the natural Tr cell-specific transcription factor Foxp3
      in naive CD4(+)CD25(-) T cells. The CD25(+) cells that emerged later only in the
      TGF-beta-treated culture failed to express CD69, so distinguishing this
      population from activated CD25(+) effector cells. The TGF-beta-treated T cells
      entered an anergic state following restimulation, as judged by enhanced induction
      of programmed death (PD)-1, as well as impaired responses in terms of
      proliferation and IL-2 production. Importantly, the TGF-beta-costimulated
      CD4(+)CD25(-) T cells, prior to conversion to CD25(+) cells, were able to
      suppress the proliferation of responder T cells via contact-dependent and
      interleukin-10-independent mechanisms. Taken together, these results demonstrate
      that the existence of TGF-beta during early phase of priming is sufficient to
      induce CD4(+)CD25(-) Tr cells with anergic and immunoregulatory activities
      equivalent to thymus-derived CD4(+)CD25(+) Tr cells, and these cells are
      programmed to be CD25(+) cells under the prolonged resting conditions. Thus, our
      findings provide a novel mechanism by which TGF-beta mediates infectious
      tolerance in the periphery.

PMID- 15237110
TI  - Induction of antigen-specific immunologic tolerance by in vivo and in vitro
      antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T
      cells.
AB  - Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to
      establish immunologic tolerance to non-self antigens. In vivo exposure of
      CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient
      environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+)
      T(R) cells, which suppressed allograft rejection mediated by subsequently
      transferred naive T cells, leading to long-term graft tolerance. The expanded
      T(R) cells, which became CD25(low) in the absence of other T cells, stably
      sustained suppressive activity, maintained expression levels of other T(R) cell
      associated molecules, including Foxp3, CTLA-4 and GITR, and could adoptively
      transfer tolerance to normal mice. Furthermore, specific removal of the T(R)
      cells derived from originally transferred CD25(+)CD4(+) T(R) cells evoked graft
      rejection in the long-term tolerant mice, indicating that any T(R) cells deriving
      from CD25(-)CD4(+) naive T cells minimally contribute to graft tolerance and that
      natural T(R) cells are unable to infectiously confer significant suppressive
      activity to other T cells. Similar antigen-specific expansion of T(R) cells can
      also be achieved in vitro by stimulating naturally present CD25(+)CD4(+) T cells
      with alloantigen in the presence of IL-2. The expanded CD25(+)CD4(+) T cells
      potently suppressed even secondary MLR in vitro and, by in vivo transfer,
      established antigen-specific long-term graft tolerance. Thus, in vivo or in
      vitro, direct or indirect ways of antigen-specific expansion of naturally arising
      Foxp3(+)CD25(+)CD4(+) T(R) cells can establish antigen-specific dominant
      tolerance to non-self antigens, and would also be instrumental in re-establishing
      self-tolerance in autoimmune disease and antigen-specific negative control of
      pathological immune responses.

PMID- 15237112
TI  - Evidence for a dual pathway of activation in CD43-stimulated Th2 cells:
      differential requirement for the Lck tyrosine kinase.
AB  - CD43 is the most abundant cell surface-expressed sialoglycoprotein on T
      lymphocytes. Despite evidence demonstrating the activation of some signaling
      components by CD43, the exact function of CD43 in T cell biology remains
      controversial. In this study, we demonstrate that the sole ligation of CD43 in
      cloned Th2 cells resulted in cytokine production, cellular proliferation, and
      upregulation of CD25 and CD69 activation markers. Similarly, cross-linking of
      CD43 on naive splenic T cells led to a significant proliferative response and an
      enhancement of the expression of CD25 and CD69 markers. These responses required
      no additional signals from other T cell molecules, including TCR. In Lck
      deficient Th2 cells, however, CD43 ligation led to IL-4 production and an
      increase in the expression of CD25 and CD69 antigens but, surprisingly, no
      proliferation. Analysis of signaling pathway components revealed that CD43
      associates with the adaptor protein SLP-76 within 30 s of activation. This
      induces the tyrosine phosphorylation of SLP-76 and promotes the recruitment and
      phosphorylation of another adaptor, Shc. The formation of this multi-component
      complex was strictly dependent on Lck. In contrast, comparison of tyrosine
      phosphorylated proteins in whole extracts of normal and Lck-deficient cells
      revealed a strikingly similar pattern of phosphorylation involving two major
      protein bands at 26 and 78 kDa. This suggests that tyrosine kinases other than
      Lck are activated by CD43 ligation. Taken together, the data support the notion
      that CD43 ligation may induce a dual pathway leading to the activation of
      different effector functions in Th2 lymphocytes.

PMID- 15237113
TI  - Acetabular remodelling after reduction in developmental dysplasia of the hip.

PMID- 15237114
TI  - Operative treatment of bilateral hip dislocation in children with arthrogryposis
      multiplex congenita.
AB  - PURPOSE: Arthrogryposis multiplex congenita (AMC) is a rare syndrome with
      multiple joint contractures. It is commonly believed that bilaterally dislocated
      hips associated with joint contractures should not be reduced, because movement
      is satisfactory, while open reduction leads to poor results. This report presents
      our experience with surgical management of bilateral dislocation of hips in
      children with AMC. METHODS: During the period 1990 to 2000, we performed open
      reduction on 8 hips of 4 children with AMC. The mean age at surgery was 23 months
      (range, 5-48 months). Open reduction and capsular plication without any bony
      procedure were performed in 4 hips (2 patients). De-rotation and varus osteotomy
      of the femur was performed in 4 hips, and Salter osteotomy of the innominate bone
      in 2 hips. The average acetabular index was 44 degrees, and the mean centreedge
      angle was -41 degrees preoperatively. RESULTS: The average follow-up period was 4
      years (range, 2-9 years). The average acetabular index and centre-edge angle were
      19 and 18 degrees, respectively at the time of last follow-up. All children could
      walk without support. One child required re-opening for redislocation of hip
      joint. The clinical results were good in 6 hips and fair in 2 hips, according to
      Severin's and McKay's classifications. CONCLUSION: Our experience shows that open
      reduction for bilateral dislocation of hips in children with AMC is a suitable
      option with generally good results. Surgery performed at earlier age gives the
      best functional outcome.

PMID- 15237115
TI  - Changing epidemiology of neonatal septic arthritis.
AB  - PURPOSE: To study the changing epidemiological pattern of micro-organisms as an
      aetiology of septic arthritis, and to correlate the pattern with the outcome of
      neonatal septic arthritis, in terms of joint function and morphology. METHODS: 15
      consecutive cases of neonatal septic arthritis of hip admitted between 1999 and
      2002 were studied. Diagnosis of septic arthritis was made on the basis of
      Morrey's criteria. All patients were treated by arthrotomy after aspiration of
      purulent fluid from the joint. Patients were followed up for a mean period of 2.4
      years. Clinical and radiological examinations were performed at follow-up.
      RESULTS: The mean age of the 15 patients was 20.35 days. 13 (87%) patients had
      primary septic arthritis, while only 2 (13%) had associated osteomyelitis.
      Culture reports revealed that the spectrum consisted of 33% gram-negative
      organisms, 7% fungal, and only 20% gram-positive organisms-Staphylococcus aureus
      in 3 patients, Klebsiella in 2 patients, one each of Proteus, Candida,
      Escherichia coli, and Enterobactor. Six patients were pus-cell positive with
      negative culture. No organism was found in 6 (40%) cases. Investigations showed
      leukocytosis, raised C-reactive protein and erythrocyte sedimentation rate in all
      15 patients. 12 patients had normal clinical and radiological parameters at
      follow-up. Three patients had delayed surgical drainage of more than 72 hours due
      to late presentation, and showed various radiological sequelae with terminal
      restriction of joint movements. CONCLUSION: There are more cases of primary
      septic arthritis than secondary septic arthritis. Clinicians should be alert of
      the aetiology shift to gram-negative organisms, in addition to fungal and gram
      positive ones. Arthrotomy to drain pus from the joint should not be delayed.
      Better long-term results can be achieved by early surgical drainage and immediate
      antibiotic coverage.

PMID- 15237116
TI  - Cementless total hip arthroplasty using an autograft of the femoral head for
      marked acetabular dysplasia: case series.
AB  - PURPOSE: To assess the short-term outcome of cementless total hip arthroplasty
      involving an autograft of the femoral head in Japanese patients. METHODS:
      Cementless total hip arthroplasty with autogenous bone block grafting was
      performed on 18 hips in 15 patients with marked acetabular dysplasia. The
      resected femoral head was used as a graft for the superior-lateral region of the
      true acetabulum. Clinical outcome was correlated with the placement of the
      acetabular component, as revealed in radiographs. RESULTS: The 13 women and 2 men
      had a mean age of 60.2 years (range, 37.0-73.0 years) at primary surgery and a
      mean follow-up duration of 3.3 years (range, 2.0-5.3 years). According to the
      classification of Crowe, 4 hips were in group I, 3 were in group II, one in group
      III, and 10 in group IV. The mean Harris Hip Score preoperatively was 45.7
      (range, 19-69) and that at follow-up was 82.5 (range, 44-100). All 15 cases
      showed a good clinical outcome. There were no major intra-operative complications
      in this series. The grafted bones united in all patients. Two patients need
      surgical revision because the lateral insertion of the acetabular component
      resulted in loosening of it. CONCLUSION: Medial insertion of the acetabular
      component provides satisfactory short-term outcomes. Lateral insertion of the
      acetabular component during total hip arthroplasty should be avoided in patients
      with marked acetabular dysplasia.

PMID- 15237117
TI  - Mini-incision total hip replacement--surgical technique and early results.
AB  - PURPOSE: To compare the results of mini-incision total hip replacement (MITHR) to
      the standard posterior approach and evaluate the advantages and disadvantages of
      MITHR. METHODS: 60 patients with osteoarthritis of the hip underwent total hip
      replacement utilising a mini-incision technique. They were compared to a matched
      cohort of patients who received the standard posterior approach. The average
      follow-up period was 14 months. The patients were compared with respect to the
      length of the incision, surgical time, intra-operative blood loss, narcotic
      requirements, length of hospital stay, requirement for walking aids, Harris hip
      score, and complications. RESULTS: The length of the skin incision for MITHR, at
      an average of 9.2 cm, was half that of the standard approach. Statistically
      significant differences were found between the 2 groups in terms of intra
      operative blood loss, length of hospital stay, and use of walking aids, all in
      favour of MITHR. There were no differences between the two approaches with regard
      to operating time, narcotic requirements, or Harris hip score. There were no
      cases of component malpositioning or major complications in the MITHR group.
      CONCLUSION: Uncemented total hip replacement can be effectively performed through
      a smaller incision utilising MITHR without increased risk of complications.
      Significant benefits include less intra-operative blood loss, shorter
      hospitalisation, and cosmesis.

PMID- 15237118
TI  - Revision of total hip arthroplasty using an anterior cortical window, extensive
      strut allografts, and an impaction graft: follow-up study.
AB  - PURPOSE: To report the outcome of revised total hip arthroplasty procedures
      involving an anterior cortical window, extensive strut allografts, and an Exeter
      impaction graft. METHOD: Eight patients (9 hips) with a mean age of 58 years
      underwent revision of total hip arthroplasty using the Exeter hip impaction graft
      system and strut allografts between 1995 and 1998. An extensile anterior approach
      was used, and an anterior cortical window was created in the femur, to remove the
      old implant. External strut allografts were attached by wires to provide cortical
      support. The mean follow-up duration was 74 months. Indications for surgery were
      aseptic loosening of previous implants in 8 hips and infection of one hip that
      had previously undergone total arthroplasty. RESULTS: 19 Dall Miles cables, 4
      ordinary cerclage wires, and 8 cerclage wires tightened with the clincher knot
      technique were used to secure the allograft to the host bone. The strut grafts
      were found to be incorporated in all cases. No wires became loose. One patient
      developed 20 degrees of angulation at the allograft-host bone junction. Using the
      method of Fowler and Gie, we found that one femoral implant had subsided 2 mm
      within the cement mantle. Two other implants had 1 mm of subsidence at the cement
      bone interface, and one patient had a major subsidence of 15 mm that required
      revision. CONCLUSION: Using an anterior cortical window in the femur to remove
      the old implant does not predispose to failure of the allograft to incorporate
      into the host bone.

PMID- 15237119
TI  - Does routine blood bone biochemistry predict vitamin D insufficiency in elderly
      patients with low-velocity fractures?
AB  - PURPOSE: Vitamin D deficiency impairs bone mineralisation and can predispose
      individuals to fractures. This study aimed at testing whether measurement of
      plasma calcium, alkaline phosphatase, and phosphate levels could detect vitamin D
      insufficiency. METHODS: During a 10-week winter period from December 2000 to
      February 2001, all elderly patients presenting to a general hospital in Brighton-
      British seaside town--with a fracture of the proximal femur and without known
      bone mineralisation problems were invited to participate in the study. RESULTS:
      23 (63.9%) of the 36 eligible patients had insufficient levels of vitamin D, with
      a plasma concentration of less than 30 nmol/L. The mean parathyroid hormone level
      was 56 pg/mL (range, 12-193 pg/mL). 11 of the 36 patients had an elevated level
      of parathyroid hormone were insufficient in vitamin D. The mean plasma
      concentration of calcium was 2.30 mmol/L (range, 2.05-2.98 mmol/L). The mean
      phosphate level was 0.98 mmol/L (range, 0.40-1.79 mmol/L), and the mean alkaline
      phosphatase level was 91 IU/L (range, 46-127 IU/L). There was poor correlation
      between vitamin D insufficiency and plasma calcium, alkaline phosphatase, or
      phosphate levels. CONCLUSION: Plasma calcium, alkaline phosphatase, and phosphate
      testing cannot detect vitamin D insufficiency. We recommend that vitamin D and
      calcium supplementation be considered for patients with low-energy hip fractures.

PMID- 15237120
TI  - Sympathetic skin response in patients with spinal cord injury.
AB  - PURPOSE: To assess the effectiveness of sympathetic skin response in evaluating
      peripheral sympathetic nerve activity of patients with spinal cord injury, and to
      report on the basic properties of sympathetic skin response. METHODS: Sympathetic
      skin response evoked by electrical stimulation was recorded from the palms and
      soles of healthy volunteers and patients with spinal cord injury. RESULTS:
      Sympathetic skin response was recorded in 17 healthy volunteers and 14 patients
      with spinal cord injury. Of the 4 waveforms, the shortest latency was obtained
      from the palm; the sympathetic skin response was 1.2 to 1.4 ms at all stimulated
      sites, 1.9 to 2.0 ms at the sole, with a difference of about 0.6 ms between the
      palm and the sole. None of the patients with spinal cord injury responded at
      either the upper or lower limbs. In patients with a thoracic cord injury, some
      responded at the upper limbs but none at the lower limbs; some responded at
      neither upper nor the lower limbs; and some responded at both upper and lower
      limbs. The conducting pathway of sympathetic skin response in the spinal cord for
      the upper limbs descends to the upper thoracic cord (T4-6), and the conducting
      pathway for the lower limbs departs from the spinal cord at the lower thoracic
      cord (T9-10). CONCLUSION: It appears that sympathetic skin response should be
      used for the evaluation and morbid investigation of the functional abnormalities
      of the sympathetic nervous system in patients with spinal cord lesions such as
      spinal cord injuries, cervical spondylosis, and spinal canal stenosis.

PMID- 15237121
TI  - How often should computed tomographic scans following cross-table lateral
      cervical films be performed?
AB  - PURPOSE: In patients with blunt trauma, a cross-table lateral cervical (CTLC)
      film is followed by a focused computed tomographic (CT) scan of the cervical
      spine to assess an area inadequately delineated by common techniques and
      suspected injuries, based on recent guidelines in the United States. The purpose
      of this study was to calculate the frequency of such supplemental CT scans and to
      evaluate the efficacy of the recent guidelines describing the use of CTLC films
      as an indicator of supplemental focused CT scanning in Japan. METHODS: A review
      of CTLC films was performed. 100 initial CTLC films with injuries and another 100
      films without injuries were evaluated for the lowest vertebra visualised on the
      CTLC film. The frequency of abnormal signs on the CTLC films was then examined.
      RESULTS: Technically adequate CTLC films that showed the upper border of the T1
      vertebra were not obtained from 70 patients with injuries and 63 patients without
      injuries. 88 patients with injuries and 28 patients without injuries had abnormal
      findings on CTLC films. Overall, 97 patients with injuries and 74 patients
      without injuries should have received supplemental CT scans. CONCLUSION: CTLC
      films require frequent supplemental use of CT, even for patients without cervical
      spine injuries. Thus, the guidelines that consider CTLC film as an indicator of
      the necessity for CT scanning are not efficient and need revision.

PMID- 15237122
TI  - Effects of ethane-1-hydroxy-1,1-diphosphonate on ossification of the posterior
      longitudinal ligament in Zucker fatty rats.
AB  - PURPOSE: Using Zucker fatty rats as an animal model, we evaluate the
      effectiveness of ethane-1-hydroxy-1,1-diphosphonate on ossification of the
      posterior longitudinal ligament by histopathologically investigating the
      prodromal, early, and advanced stages of ossification of the spinal ligaments.
      METHODS: 73 Zucker fatty rats were allocated to the ethane-1-hydroxy-1,1
      diphosphonate group (n=33) and the control group (n=40). The former group was fed
      ethane-1-hydroxy-1,1-diphosphonate daily. The feed was given starting 2 months
      after birth and continued until the rats were killed at 3 to 18 months later.
      Chemical analysis of the blood, radiographic tests, and histopathological
      examination were then conducted for both groups. RESULTS: The results showed that
      ossification of the spinal ligaments involved excessive cartilage cell
      proliferation around areas affected by enthesitis; enlargement of the
      fibrocartilage tissue layer; ligament thickening; calcification of the matrix
      around the cartilage cells; and ossification of the spinal ligaments through
      enchondral ossification. Radiographic examinations showed that osteoproliferation
      in vertebral bodies in rats receiving ethane-1-hydroxy-1,1-diphosphonate was
      generally suppressed compared with controls, whereas histopathological
      examinations found no clear difference in cartilage cell proliferation in areas
      affected by enthesitis between the two groups, indicating the absence of
      calcification or osteo-proliferation in areas affected by enthesitis for the rats
      receiving ethane-1-hydroxy-1,1-diphosphonate. CONCLUSION: Ethane-1-hydroxy-1,1
      diphosphonate is effective in suppressing progressive ligament ossification.

PMID- 15237123
TI  - Clinical and immunohistochemical characteristics of benign giant cell tumour of
      bone with pulmonary metastases: case series.
AB  - PURPOSE: Giant cell tumour of bone with pulmonary metastases is rare. However,
      some patients die of pulmonary metastases, and histological examination cannot
      distinguish between benign tumour and malignant metastases. In this study, we
      present clinical and immunohistochemical findings associated with giant cell
      tumour of bone with pulmonary metastases. METHODS: Five patients with benign
      giant cell tumour of bone with pulmonary metastases (one man and 4 women) were
      studied. Patients' ages ranged between 20 and 23 years (mean age, 21.8 years).
      Tumours were in the distal femur in 2 cases, and in the proximal tibia, distal
      tibia, and lumbar spine in one case each. The tissue specimens from primary
      tumours, recurrent tumours, and pulmonary metastases were studied using
      immunohistochemical techniques. RESULTS: Three of the 5 primary tumours were of
      the spontaneous regression or growth cessation type, or the continuously slow
      growing type, showing 4.2% to 6.2% of positive cells for Ki-67 after
      immunohistochemical staining. However, 2 patients with the rapid-growing type of
      disease died of pulmonary metastases; their primary, recurrent, and metastatic
      tumour specimens contained 9.0% to 11.5% of positive cells for Ki-67. CONCLUSION:
      Three of the 5 primary tumours had a benign clinical pattern and
      immunohistochemistry. Two of the 5 patients died of pulmonary metastases, which
      had an aggressive clinical pattern and a high prevalence of positive cells in Ki
      67. Examination of Ki-67 should be carried out for aggressive type of giant cell
      tumour.

PMID- 15237125
TI  - Midshaft clavicular non-unions treated with the Herbert cannulated bone screw.
AB  - PURPOSE: To assess an alternative technique for the treatment of midshaft non
      unions of the clavicle. METHODS: Five patients with symptomatic non-unions of the
      clavicle were treated with open reduction and intramedullary fixation by using a
      Herbert cannulated bone screw. Autogenous bone grafting was applied in one case
      and decortication in the other 4 cases. RESULTS: Review of the clinical and
      radiological documentation at a mean time of 13 months (range, 9-26 months)
      postoperatively shows that union was achieved in all 5 cases. There were no
      complications related to the operation, and no patient needed removal of the
      implant for protrusion, loosening, or any other cause. CONCLUSION: Midshaft non
      unions of the clavicle can be treated successfully using the Herbert cannulated
      bone screw, which avoids the need for a second operation to remove the implant
      after bone union.

PMID- 15237124
TI  - Diagnostic utility of waveform analysis of compound muscle action potentials for
      carpal tunnel syndrome.
AB  - PURPOSE: To determine the diagnostic utility of waveform analysis of compound
      muscle action potentials (CMAP) for carpal tunnel syndrome (CTS). METHODS: A
      total of 131 hands in 71 patients diagnosed with CTS (grouped according to
      severity) and 80 hands in 44 normal subjects were evaluated using nerve
      conduction test through the carpal tunnel combined with waveform analysis of
      CMAP. RESULTS: Compared to normal subjects, the sensory nerve conduction velocity
      and mean frequency of the CMAP waveform were significantly reduced in patients
      with CTS. Compared with distal motor latency and sensory nerve conduction
      velocity, the mean frequency of the CMAP decreased significantly with increasing
      clinical severity. CONCLUSION: This study suggests that waveform analysis of CMAP
      is of diagnostic value in CTS, and is also of value in objective evaluation of
      postoperative recovery of carpal median nerve dysfunction.

PMID- 15237126
TI  - Comparison of two methods of percutaneous pin fixation in displaced supracondylar
      fractures of the humerus in children.
AB  - PURPOSE: To conduct a prospective randomised controlled study to compare the
      stability and risk of nerve injury between fractures treated by medial-lateral
      pin fixation and those treated by 2-lateral pin fixation. METHODS: Patients with
      displaced supracondylar fractures admitted between May 2000 and December 2001
      were recruited into the study. They were randomised to treatment either with
      medial-lateral pin fixation (n=34) or with 2-lateral pin fixation (n=32).
      RESULTS: 66 children with the mean age of 5.78 years were admitted during the
      study period. 11 of them were lost to follow-up. The mean follow-up period of the
      remaining 55 patients was 8.93 months. The difference in the carrying angle
      between injured and normal elbows was 3.57 degrees and 3.70 degrees in medial
      lateral pin fixation and 2-lateral pin fixation, respectively. The extension and
      flexion loss was 7.14 degrees and 8.68 degrees respectively in medial-lateral pin
      fixation, and 7.11 degrees and 11.26 degrees respectively in 2-lateral pin
      fixation. The Baumann angle difference was 5.96 degrees in medial-lateral pin
      fixation, and 5.30 degrees in 2-lateral pin fixation. The difference in the
      medial epicondylar epiphyseal angle was 6.07 degrees in medial-lateral pin
      fixation and 6.92 degrees in 2-lateral pin fixation. Statistical analyses show
      that these differences are not significant. Five iatrogenic ulnar nerve injuries
      developed in the group treated by medial-lateral pin fixation, while 2 ulnar
      nerve and one radial nerve injuries were seen after 2-lateral pin fixation. Again
      the differences were not statistically significant. CONCLUSION: Both methods of
      fixation were comparable in terms of stability, duration of bone healing, and
      risks of injury to the nerve.

PMID- 15237127
TI  - A new clinical test for radial tunnel syndrome--the Rule-of-Nine test: a
      cadaveric study.
AB  - PURPOSE: Radial tunnel syndrome refers to pain on the lateral aspect of the
      forearm as a result of compression of the posterior interosseous nerve within a
      tunnel with specific anatomical boundaries. Diagnosis of the condition is
      difficult because of its close association with lateral epicondylitis, which
      warrants different methods of treatment. Based on a cadaveric study, a new
      clinical test, the Rule-of-Nine test, is proposed to improve the diagnostic
      accuracy in radial tunnel syndrome. The test involves constructing 9 equal
      squares on the anterior aspect of the forearm and noting those squares where
      tenderness can be elicited. METHODS: 19 upper limbs were dissected to delineate
      the path of the posterior interosseous nerve through the radial tunnel, and the
      relationship of the path of the nerve with the 9 squares. RESULTS: A consistent
      mapping of the posterior interosseous nerve to the lateral column of 3 squares
      was observed. CONCLUSION: The Rule-of-Nine test is proposed as a reliable method
      of diagnosing radial tunnel syndrome.

PMID- 15237128
TI  - Single photon emission computed tomography scanning in the diagnosis of knee
      pathology.
AB  - PURPOSE: To evaluate the role of single photon emission computed tomography
      (SPECT) bone scan for the diagnosis of knee lesions in routine clinical practice.
      METHODS: 40 consecutive case records were examined in patients who underwent a
      SPECT scan prior to knee arthroscopy in routine clinical practice. The accuracy
      of clinical examination, SPECT scan results, and arthroscopic findings (as the
      gold standard) in diagnosing knee lesions were compared. RESULTS: The sensitivity
      of SPECT scans in detecting medial meniscal, lateral meniscal, anterior cruciate
      ligament lesions, osteochondral defects, and chondromalacia patellae was 77%,
      14%, 33%, 50%, and 74%, respectively. The specificities for the same structural
      lesions were high at 89%, 94%, 97%, 94%, and 69%, respectively. CONCLUSION: SPECT
      bone scan appears to be useful in the diagnosis of knee pathology in routine
      practice and in selecting patients for arthroscopy, especially most useful for
      the diagnosis of medial meniscal tears.

PMID- 15237129
TI  - Ilizarov ring fixation and fibular strut grafting for C3 distal femoral
      fractures.
AB  - PURPOSE: To evaluate treatment outcome following surgical repair of C3 distal
      femoral fractures using autogenous fibular strut, cortico-cancellous bone
      grafting, and Ilizarov ring fixation. METHODS: A total of 15 patients with type
      C3 fractures (supracondylar and intercondylar fractures, with multiplane
      articular injury) underwent surgical repair at St. John's Medical College
      Hospital between 1994 and 2001, using autogenous fibular strut, cortico
      cancellous bone grafting, and Ilizarov ring fixation. 13 were seen for ongoing
      follow-up and assessment. Definitive surgery was undertaken at a mean of 3 weeks
      after admission. Postoperatively, weight-bearing and mobilisation exercise were
      begun in 2 to 4 weeks. RESULTS: The mean follow-up period was 47 months. Union
      was achieved in all 13 cases by an average time of 19 weeks. At the last follow
      up, the mean range of knee motion was 77 degrees. Assessment of functional
      outcome (using Neer's scoring criteria) revealed 10 cases with good or
      satisfactory outcomes, and 3 cases with poor or unsatisfactory results.
      CONCLUSION: Surgical repair with a fibular strut, cortico-cancellous bone graft
      and Ilizarov ring fixation appears a suitable treatment option for C3 distal
      femoral fractures.

PMID- 15237130
TI  - Therapeutic results of acromioclavicular joint dislocation complicated by rotator
      cuff tear.
AB  - PURPOSE: To evaluate the operative findings and postoperative results of one
      stage repair on patients with acromioclavicular joint dislocation complicated by
      rotator cuff tear. METHODS: Between 1992 and 1999, one-stage repair was performed
      on 5 patients with acromioclavicular joint dislocation complicated by rotator
      cuff tears. Modified Cadenat procedure for acromioclavicular joint dislocation,
      and McLaughlin procedure for rotator cuff tear, were performed on these patients.
      Postoperative results at the final examination were assessed according to the
      criteria for therapeutic effects on shoulder joint disorders of the Japanese
      Orthopaedic Association. RESULTS: There was partial-thickness cuff tear in one
      patient, and full-thickness cuff tear in the remaining 4 patients. In all
      patients, tears were located only in the supraspinatus tendon, and were medium or
      small ones with maximal diameter of 3 cm or less. After a mean follow-up period
      of 56 months (range, 36-79 months), all patients were assessed to have excellent
      results. No patient showed a good reduction of the acromio-clavicular joint.
      CONCLUSION: For patients successfully treated by one-stage repair, satisfactory
      results were obtained without pain or disturbance in activities of daily living.

PMID- 15237131
TI  - Perioperative and rehabilitation outcome after lower-limb amputation in elderly
      Chinese patients in Hong Kong.
AB  - PURPOSE: Major amputation of the lower limb is considered the last resort when
      limb salvage is impossible. The aim of this study is to determine the morbidity,
      mortality, and rehabilitation outcome of patients that underwent a lower-limb
      amputation. METHODS: A retrospective cohort study was conducted among 100 elderly
      patients who underwent a total of 120 lower-limb amputations in a regional
      hospital in Hong Kong from 1996 to 2001. RESULTS: The mean age of the amputees
      was 77.9 years; 58 were female. 95% of the amputations were performed because of
      infection with or without vascular compromise; 55 transfemoral and 60 transtibial
      amputations contributed 96% of the case mix. Some 43% of patients experienced
      early complications and 12% required re-amputation. The early (30-day) mortality
      rate was 15%. Only 55% of the amputees survived after 4 years. A 44% return-home
      rate was achieved. However, only 11% of the amputees could walk without help from
      other people. Although prostheses were issued to 42% of the survivors, compliance
      was only 53%; 24% of the survivors lost their remaining leg within 2 years.
      CONCLUSION: The outcome of major lower-extremity amputation remains poor. Efforts
      should be made to retain these limbs. When it is proven impossible, one should
      strive to preserve the knee joint whenever feasible.

PMID- 15237132
TI  - Composite vascularised osteocutaneous fibula and sural nerve graft for severe
      open tibial fracture--functional outcome at one year: a case report.
AB  - Management of severe open tibial fracture with neurovascular injury is difficult
      and controversial. Primary amputation is an acceptable option as salvaging the
      injured, insensate, and ischaemic limb may result in chronic osteomyelitis and
      non-functional limb. We report a case of open tibial fracture associated with
      segmental bone and soft tissue loss, posterior tibial nerve and artery injuries,
      which was further complicated by chronic osteo-myelitis treated with composite
      vascularised osteocutaneous fibula and sural nerve graft. Functional outcome of
      the injured limb at one-year follow-up was satisfactory: the patient was capable
      of achieving full weightbearing and was able to appreciate crude touch, pain,
      proprioception, and temperature at the plantar aspect of the foot. There was no
      pressure sore or ulceration.

PMID- 15237133
TI  - Cross-linked polyethylene and bisphosphonate therapy for osteolysis in total hip
      arthroplasty: a case report.
AB  - A 39-year-old woman underwent bilateral total hip arthroplasty with conventional,
      ethylene oxide-sterilised liners when she was a subject in a radiostereometric
      analysis study. Within 2 years she had rapid polyethylene wear with aggressive,
      asymptomatic, and periprosthetic osteolysis on both sides. Oral alendronate
      therapy halted the progression of osteolysis over a year and revision to cross
      linked polyethylene liners was then undertaken while one stem was curettaged and
      the other revised. Radiostereometric analysis revealed a 96% reduction in wear
      rate over 2 years with the cross-linked liners. On stopping alendronate
      treatment, aggressive osteolysis recurred on the curretaged but not on the
      revised femur.

PMID- 15237134
TI  - Bony entrapment of ulnar nerve after closed forearm fracture: a case report.
AB  - We report a case of ulnar nerve palsy following forearm fracture in a 13-year-old
      girl. Significant anterior angulation and displacement of the ulna were noted.
      Operation was performed 3 months after the injury, when no recovery of numbness
      and claw hand deformity were demonstrated. Intra-operatively the ulnar nerve was
      found to be embedded between fragments of the fractured ulna, which showed lack
      of callus formation on the preoperative radiograph. The patient achieved complete
      recovery of sensory and motor functions 4 months after the surgery.

PMID- 15237135
TI  - Traumatic anterior dislocation of the hip associated with ipsilateral femoral
      shaft fracture in a child: a case report.
AB  - Traumatic anterior dislocation of the hip joint in children is rare, and only one
      case with ipsilateral femoral fracture has been reported in Japan. We report a
      case of such dislocation and a review of the literature. The patient was a 31
      month-old girl who was injured in a car accident while asleep on a tilted front
      passenger seat. Radiographic examination showed dislocation of the right
      obturator foramen and transverse fracture of the ipsilateral femoral shaft. The
      dislocation of the right hip was easily reduced without anaesthesia during
      radiography. We applied Bryant traction after reduction for 4 weeks, followed by
      cast application for 3 weeks. Walking with support and full weightbearing were
      permitted 14 weeks and 16 weeks after the injury, respectively. Radiography at
      4.5 years after the injury showed a mildly enlarged right femoral head and femur
      overgrowth of approximately 8 mm. Magnetic resonance imaging showed no evidence
      of suspected avascular necrosis of the femoral head. The patient has no
      subjective or objective symptoms, and is able to engage in all usual activities.
      The detailed mechanism of the injury is unknown. We assume that the lower leg was
      dislocated through abduction during flexion, or abducent, external flexion,
      considering that the child was sleeping at the time of the accident. Since she
      was hurled to the back seat, it was assumed that strong external force was
      vertically added to the femur, which caused the abducent force.

PMID- 15237136
TI  - An age- and sex-controlled matched pair analysis of T scores in ethnic Indians
      with hip fractures.

PMID- 15237137
TI  - Thiocyanates of nickel and caesium: Cs2NiAg2(SCN)6.2H2O and CsNi(SCN)3.
AB  - The crystal structures of dicaesium nickel disilver hexathiocyanate dihydrate,
      Cs2NiAg2(SCN)6.2H2O, (I), and caesium nickel trithiocyanate, CsNi(SCN)3, (II),
      have been determined by single-crystal X-ray diffraction at 273 K. Compounds (I)
      and (II) are monoclinic, with P21/c and P21/n symmetry, respectively. In (I), the
      Ni atom lies on an inversion centre; in (II), there are two independent Ni atoms,
      each of which lies on an inversion centre. The coordination polyhedra and the
      bonding schemes in the structures are discussed.

PMID- 15237138
TI  - Lithium vanadate Li(3+x)V6O13 at low temperature.
AB  - The structure of Li(3+x)V6O13 [x = 0.24 (3)] at 95 K has been solved and refined
      using single-crystal X-ray diffraction. The refined lithium content corresponds
      to two fully occupied Li sites and one partially occupied Li site. A doubling of
      the c axis is observed upon cooling from room temperature, and this change is
      associated with shifts of the V atoms. The resulting space group is C2/c. The Li
      disorder present in the Li3V6O13 phase at room temperature is also observed in
      the low-temperature phase reported here.

PMID- 15237139
TI  - Rubidium metaborate, Rb3B3O6.
AB  - Rubidium metaborate, Rb3B3O6, was obtained by the reaction of Rb2CO3 and BN using
      a radiofrequency furnace at a maximum reaction temperature of 1173 K. The crystal
      structure has been determined by single-crystal X-ray diffraction. The space
      group is R3c, with all atoms positioned on a twofold axis (Wyckoff site 18e). The
      ionic compound is isotypic with Na3B3O6, K3B3O6 and Cs3B3O6.

PMID- 15237140
TI  - Bis[benzidinium(1-)] pentamolybdate.
AB  - The title compound, [(C12H13N2)2[Mo5O16]]n, was synthesized under hydrothermal
      conditions. The structure contains a two-dimensional layer, constructed from
      [(Mo4O14)n]4n- chains linked through MoO6 octahedra, which lie across twofold
      axes. The [(Mo4O14)n]4n- chain consists of [Mo4O14]4- clusters connected to one
      another by sharing their MoO5 square-pyramidal and MoO6 octahedral vertices in an
      anti disposition. The layers are linked by the cation, to which they are
      connected via N-H...O hydrogen bonds.

PMID- 15237141
TI  - Bis[tris(ethylenediamine)cobalt(III)] dichlorobis[mu-(1
      hydroxyethylidene)diphosphonato(4-)]diruthenium(II,III)(Ru-Ru) chloride
      trihydrate.
AB  - In the title compound, [Co(C2H8N2)3]2[Ru2(C2H4O7P2)2Cl2]Cl.3H2O, the building
      unit contains two crystallographically independent dinuclear [Ru2(hedp)2Cl2]5-
      anions, where hedp [viz. (1-hydroxyethylidene)diphosphonate] serves as a bis
      chelating bridging ligand, two types of [Co(en)3]3+ cations, one uncoordinated Cl
      anion and five water molecules of crystallization. The [Ru2(hedp)2Cl2]5- anions
      are connected to one another, forming one-dimensional chains along the a axis.
      The [Co(en)3]3+ cations are located between these chains and lie across inversion
      centres. An extensive series of hydrogen bonds lead to the formation of a three
      dimensional supramolecular network structure, with channels generated along the
      [100] direction. The uncoordinated water molecules and Cl- anions reside in these
      channels.

PMID- 15237142
TI  - Bis[tris(pyridin-2-yl)methanol-kappa2N,N']palladium(II) dinitrate at 150 and 298
      K.
AB  - The title complex, [Pd[(py)3COH]2](NO3)2, where (py)3COH is tris(pyridin-2
      yl)methanol (C16H13N3O), studied at 150 and 298 K, has the potentially tridentate
      ligands present as bidentate ligands, with the Pd atom at a centre of symmetry.
      At 150 K, the Pd-N distances are 2.022 (3) and 2.026 (3) A. The mean planes of
      the coordinated pyridine groups form dihedral angles of 42.1 (1) and 45.3 (1)
      degrees (at 150 K) with the coordination plane; the uncoordinated rings situated
      either side of the coordination plane form dihedral angles of 42.2 (1) degrees
      with it. The nitrate ions are regular and interact weakly with the hydroxyl
      group.

PMID- 15237143
TI  - A novel Na-O-Ni-O-Ni bridging complex of Cl-HXTA, where Cl-HXTA is 2,6
      bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolate.
AB  - In the structure of the title compound, heptaaqua-1kappa3O,2kappa2O,3kappa2O-(mu3
      2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolato
      1kappaO;2kappa4O,O',N,O1;3kappa4O1N',O",O"')dinickel(II)sodium(I) pentahydrate,
      [NaNi2(C16H14ClN2O9)(H2O)7].5H2O or [Ni2(Cl-HXTA)(H2O)4[Na(H2O)3]].5H2O, the
      trinuclear complex unit consists of two distorted NiNO5 octahedra bridged by a
      phenolate O atom and an NaO4 tetrahedron bridged to one of the Ni octahedra by a
      carboxylate O atom. There are four intramolecular hydrogen bonds forming four six
      membered rings in the complex and the complex molecules are connected to each
      other by a very complicated hydrogen-bond network.

PMID- 15237144
TI  - Bis[tris(1-methyl-1H-imidazol-2-yl)phosphine-kappa3N3]iron(II)
      tetrachloroferrate(II) methanol tetrasolvate (ca 153 K) and bis[tris(1-methyl-1H
      imidazol-2-yl)methanol-kappa3N3]iron(III) bis[tetrachloroferrate(III)] chloride
      (redetermination, ca 153 K).
AB  - The first of the title compounds, [Fe(C12H15N6P)2][FeCl4].4CH4O, is the first
      homoleptic bis(ligand)iron(II) species reported for this phosphorus bridgehead
      ligand; interestingly, the complex is isomorphous with its tris(1-methyl-1H
      imidazol-2-yl)methanol counterpart, the second of the title compounds,
      [Fe(C13H16N6O)2][FeCl4]2Cl. In both compounds, the Fe atom of the cation lies on
      an inversion centre. The structure determinations presented here allow an
      interesting comparison of iron(II) and iron(III) species in similar coordination
      environments.

PMID- 15237145
TI  - Dichloro(methanol-kappaO)[(methoxy)tris(1-methyl-1H-imidazol-2-yl)methane
      kappa2N3]iron(II) (ca 153 K).
AB  - In the quasi-trigonal-bipyramidal environment of the five-coordinate Fe(II) atom
      in the title compound, [FeCl2(C14H18N6O)(CH4O)], the methanol and one of the N
      atom donors of the potentially tridentate ligand are disposed axially: Fe
      N(axial) is 2.149 (2) A, Fe-N(equatorial) is 2.108 (2) A and N-Fe-O is 174.14 (7)
      degrees.

PMID- 15237146
TI  - Tris[bis(1-methyl-1H-imidazol-2-yl)methanone-kappa2N3]iron(II) dichloride 5.5
      hydrate, cis-bis[bis(1-methyl-1H-imidazol-2-yl)methanone
      kappa2N3]dichloroiron(II) (ca 153 K) and di-mu-chloro-bis[[bis(1-methyl-1H
      imidazol-2-yl)methanone-kappa2N3]chloroiron(II)] methanol disolvate (ca 300 K).
AB  - The first of the title compounds, [Fe(C9H10N4O)3]Cl2.5.5H2O, is the first
      structurally characterized homoleptic tris[bis(imidazol-2-yl) ketone]-metal
      complex to be structurally defined. In the second of the title compounds,
      [FeCl2(C9H10N4O)2], a pair of monodentate donors supplants one of the bidentate
      ligands. In the third complex, [Fe2Cl4(C9H10N4O)2].2CH3OH, a centrosymmetric
      binuclear compound with a pair of bridging chloride ligands, the introduction of
      a third chloro ligand results in five-coordination about each of the metal atoms;
      the environments of the latter are square pyramidal, with a chloro ligand at the
      apex and the two bidentate arrays about the base of the pyramid.

PMID- 15237147
TI  - Diacetato-kappa2O-bis[(S)-1-(4-fluorophenyl)ethylamine-kappaN]palladium(II) and
      di-mu-acetato-kappa4O:O'-bis[[(S)-2-(1-aminoethyl)-5-fluorophenyl
      kappa2C1,N]palladium(II)] benzene hemisolvate.
AB  - Complexes of the composition trans-[Pd(L)2(OAc)2] have been postulated as
      intermediates during cyclopalladation. The first structural characterization of
      such a precursor has now been achieved and its role in the reaction sequence has
      been established. Diacetato-kappa2O-bis[(S)-1-(4-fluorophenyl)ethylamine
      kappaN]palladium(II), [Pd(O2CMe)2(4-FC6H3CHMeNH2)2] or [Pd(C2H3O2)2(C8H10FN)2],
      (I), was obtained from palladium(II) acetate and (S)-NH2CHMeC6H3F-4 in a 1:2
      molar ratio. The intermediate was then reacted with additional palladium(II)
      acetate to give the acetate-bridged dinuclear complex di-mu-acetato-kappa4O:O'
      bis[[(S)-2-(1-aminoethyl)-5-fluorophenyl-kappa2C1,N]palladium(II)] benzene
      hemisolvate, [Pd(4-FC6H3CHMeNH2)2(mu-O2CMe)]2.0.5C6H6 or
      [Pd2(C8H9FN)2(C2H3O2)2].0.5C6H6, (II).

PMID- 15237148
TI  - Carbonyl(5-nitrotropolonato-kappa2O1,O2)(triphenylphosphine-kappaP)rhodium(I).
AB  - The molecule of the title complex, [Rh(5-NO2trop)(C18H15P)(CO)] (5-NO2trop is 2
      hydroxy-5-nitrocyclohepta-2,4,6-trienone, C7H4NO4), has a distorted square-planar
      geometry. Strong intramolecular and weak intermolecular hydrogen bonding is
      observed, with H...O distances of the order of 2.25 and 2.55 A, respectively. The
      Rh-CO, Rh-O (trans to CO), Rh-O (trans to P) and Rh-P bond distances are 1.775
      (7), 2.072 (4), 2.068 (4) and 2.2397 (17) A, respectively, the O-Rh-O angle is
      77.09 (16) degrees and the bidentate O-C-C-O torsion angle is 1.5 (7) degrees.

PMID- 15237149
TI  - Potassium p-nitrophenyl sulfate.
AB  - The crystal structure of the title compound, K+.C6H4NO6S-, is built up from p
      nitrophenyl sulfate anions and potassium cations. Adjacent anions form dimers,
      which are linked together in a three-dimensional network via short C-H...O
      contacts. The coordination sphere of the K+ ions may be described as a distorted
      square antiprism. The crystal structure is further stabilized by pi-pi stacking
      interactions between the aryl rings.

PMID- 15237150
TI  - Iodo[phthalocyaninato(2-)]manganese(III) bridged by a neutral I2 molecule.
AB  - The title manganese(III) phthalocyaninate (Pc) complex, viz.
      iodo[phthalocyaninato(2-)]manganese(III) hemi(diiodine), [Mn(C32H16N8)I].0.5I2 or
      (MnPcI)2.I2, was obtained from the reaction of pure powdered manganese with
      phthalonitrile under oxidation conditions of iodine vapour. The
      phthalocyaninato(2-) residue is not strictly planar and the Mn atom is five
      coordinate, having distorted square-pyramidal geometry and residing 0.262 (2) A
      above the plane defined by the four isoindole N atoms of the phthalocyaninate
      macrocycle. The neutral I2 molecule bridges the iodo[phthalocyaninato(2
      )]manganese(III) molecules, forming a centrosymmetric dimeric structure.

PMID- 15237151
TI  - Bis(2-methylimidazolium) hydroxodiphosphatoaluminium.
AB  - The title compound, (C4H7N2)2[AlP2O7(OH)], is a one-dimensional extended-chain
      aluminophosphate prepared by a solvothermal synthesis from an alcohol system. The
      infinite [AlP2O7(OH)]2- chains composed of AlO4, PO2(=O)2 and PO2(=O)(OH)
      tetrahedra are linked via hydrogen bonds to the 2-methylimidazolium cations.

PMID- 15237152
TI  - Diaquabis(pyridine-2-carboxamide-kappa2N1,O2)nickel(II) disaccharinate
      tetrahydrate.
AB  - In the crystal structure of the title compound,
      [Ni(C6H6N2O)2(H2O)2](C7H4NO3S)2.4H2O or [Ni(pia)2(H2O)2](sac)2.4H2O (pia is
      picolinamide or pyridine-2-carboxamide, and sac is the saccharinate anion), the
      Ni2+ cation, located on a centre of symmetry, is coordinated by two symmetry
      related aqua ligands together with a pair of symmetry-related bidentate pia
      molecules and exhibits a distorted octahedral environment. The unique unligated
      sac anion in the asymmetric unit resides on a general position and has a single
      negative charge. The coordinated water molecules link the sac ions to the metal
      complex via O-H...O hydrogen bonds. In addition, the sac ions are linked to the
      metal complex via intermolecular pi-pi interactions between the benzene ring of
      the sac ion and the pyridine ring of a pia ligand. Each uncoordinated water
      molecule is hydrogen bonded to sac moieties through O-H...O and O-H...N hydrogen
      bonds.

PMID- 15237153
TI  - Bis(mu-6-hydroxypicolinato)-mu-oxo-bis[dipyridinemanganese(III)] monohydrate.
AB  - The title compound, [Mn2(mu-O)(C6H3NO3)2(C5H5N)4].H2O, was isolated from the
      reaction of 2,6-pyridinedicarboxylic acid with [Mn12O12(CH3COO)16(H2O)4] in
      pyridine. The dimanganese complex has twofold symmetry; the MnIII atoms are
      bridged by one oxo and two amidate ligands and show compressed octahedral Jahn
      Teller distortion. The molecular packing comprises a three-dimensional structure
      constructed by means of extensive intermolecular interactions, including three
      kinds of hydrogen bonds and pi-pi interactions.

PMID- 15237154
TI  - [Cu(C8H16N4O2)0.5[N(CN)2]]n, a novel ladder-like coordination polymer.
AB  - A new polymeric copper complex, viz. catena-poly[[[mu-N,N'-bis(3
      aminopropyl)oxamidato-kappa6N,N',O:N",N"',O']dicopper(II)]-di-mu-dicyanamido
      1:1'kappa2N1:N5;2:2'kappa2N1:N5], [Cu2(C8H16N4O2)(C2N3)2]n or
      [Cu(oxpn)0.5[N(CN)2]]n [where H2oxpn is N,N'-bis(3-aminopropyl)oxamide], has been
      synthesized by the reaction of Cu(oxpn), [Cu(ClO4)2].6H2O and NaN3. In the
      crystal structure, the Cu atom is five-coordinate and has a square-pyrimidal (SP)
      configuration. In the polymer, dicyanamide (dca-) groups link CuII cations in a
      mu-1,5-bridging mode, generating novel ladders in which each step is composed of
      dimeric [Cu2(oxpn)]2+ cations. Abundant hydrogen bonds connect the polymer
      ladders into a two-dimensional network structure.

PMID- 15237155
TI  - Bis[N,N'-bis(diphenylmethylene)ethylenediamine-kappa2N,N']copper(I)
      dichlorocuprate(I).
AB  - The 1:1 adduct of N,N'-bis(diphenylmethylene)ethylenediamine (bz2en) with
      copper(I) chloride, viz. [Cu(C28H24N2)2][CuCl2], has been synthesized. The
      structure contains cationic moieties of CuI ions (Cu on a twofold axis)
      coordinated to four N atoms of two bz2en molecules (in a distorted tetrahedron)
      and linear dichlorocuprate(I) anions (with Cu on an inversion centre). These
      cations and anions are packed in columns along b. The packing of the cation and
      anion columns involves a significant C-H...Cl interaction and four short
      intermolecular C-H...pi contacts, two of which are between cation columns.

PMID- 15237156
TI  - Cobalt(II), nickel(II) and copper(II) complexes of isoquinoline-3-carboxylate.
AB  - The crystal structures of the title complexes, namely trans-bis(isoquinoline-3
      carboxylato-kappa2N,O)bis(methanol-kappaO)cobalt(II), [Co(C10H6NO2)2(CH3OH)2],
      and the corresponding nickel(II) and copper(II) complexes,
      [Ni(C10H6NO2)2(CH3OH)2] and [Cu(C10H6NO2)2(CH3OH)2], are isomorphous and contain
      metal ions at centres of inversion. The three compounds have the same distorted
      octahedral coordination geometry, and each metal ion is bonded by two quinoline N
      atoms, two carboxylate O atoms and two methanol O atoms. Two isoquinoline-3
      carboxylate ligands lie in trans positions, forming the equatorial plane, and the
      two methanol ligands occupy the axial positions. The complex molecules are linked
      together by O-H...O hydrogen bonds between the methanol ligands and neighbouring
      carboxylate groups.

PMID- 15237157
TI  - A dinuclear CoII complex: bis(mu-dihydrogen phosphato-kappa2O:O')bis[(bipyridine
      kappa2N,N')(dihydrogen phosphato-kappaO)cobalt(II)].
AB  - The title compound, [Co2(H2PO4)4(C10H8N2)2], is dinuclear, centred on a symmetry
      centre of the P1 space group. Each Co atom has a distorted square-pyramidal
      coordination involving two N atoms from a bipyridine molecule and three O atoms
      from two bridging and one terminal dihydrogen orthophosphate anion. The molecular
      structure and packing are stabilized by intermolecular hydrogen-bond
      interactions.

PMID- 15237158
TI  - Poly[[[(1,10-phenanthroline-kappa2N,N')zinc(II)]-mu3-5-hydroxyisophthalato
      kappa4O,O':O":O"'] monohydrate].
AB  - In the title compound, [[Zn(C8H4O5)(C12H8N2)].H2O]n or [[Zn(OH-BDC)(phen)].H2O]n
      (where OH-H2BDC is 5-hydroxyisophthalic acid and phen is 1,10-phenanthroline),
      the Zn atoms are coordinated by two N atoms from the phen ligands and by four O
      atoms from hydroxyisophthalate ligands in a highly distorted octahedral geometry,
      with Zn-O distances in the range 2.042 (4)-2.085 (5) A and Zn-N distances of
      2.133 (5) and 2.137 (5) A. The [[Zn(OH-BDC)(phen)].H2O]n infinite zigzag polymer
      forms a helical chain of [Zn2(OH-BDC)2]n units. Face-to-face pi-pi interactions
      (3.60-3.75 A) occur between two phen rings belonging to the same helical chain.
      Consolidation of the packing structure is achieved by O-H...O hydrogen-bonding
      interactions between the carboxylate O atoms, the hydroxyl group and the water
      molecule, forming two-dimensional sheets.

PMID- 15237159
TI  - Dichloro(norbornadiene)platinum(II): a comparison with
      dichloro(cyclooctadiene)platinum(II).
AB  - The crystal structure of the title compound, (bicyclo[2.2.1]hepta-2,5
      diene)dichloroplatinum(II), [PtCl2(C7H8)], has been determined from single
      crystal X-ray analysis. The coordination sphere about the Pt atom is pseudo
      square planar, with shorter Pt-C distances than in the corresponding
      dichloro(cyclooctadiene)platinum(II) complex.

PMID- 15237160
TI  - [[Ba2(C2O4)(H2O)6](NCS)2]n: a layered mixed-anion barium oxalate.
AB  - We present the first example of a compound containing Ba2+, C2O42-, water and
      some additional halide or pseudo-halide anions, viz. hexa-mu2-aqua-mu6-oxalato
      dibarium(II) diisothiocyanate, [[Ba2(C2O4)(H2O)6](NCS)2]n. The structure consists
      of positively charged planar covalent layers of Ba2+ cations, oxalate anions and
      water molecules. The first coordination sphere of the Ba2+ cation contains six
      water molecules and four O atoms from two planar oxalate anions. The oxalate
      anion lies on an inversion centre and is coordinated to six Ba2+ cations, each
      donor O atom being bonded to two cations. Pairs of water molecules are
      coordinated by two Ba2+ cations. The layers are interspersed with non-coordinated
      NCS- anions.

PMID- 15237161
TI  - A fluorophenylboron-functionalized zirconium silsesquioxane complex.
AB  - Bis(eta5-cyclopentadienyl)[rel-(1R,5S,7R,14S)-(1,3,5,7,9,11,14-heptacyclopentyl
      7,14-dioxidotricyclo[7.3.3(1,9).1(5,11)]heptasiloxan-3
      yloxy)bis(pentafluorophenyl)borane2-]zirconium, [Zr(C5H5)2(C47H63BF10O12Si7)],
      consists of [ZrCp2] (Cp is cyclopentadienyl) and [(C6F5)2B] moieties bound to a
      silsesquioxane core. The silsesquioxane binds to the Zr atom through two of its O
      atoms to form a distorted tetrahedron. The [(C6F5)2B] moiety is bound to the
      silsesquioxane through an O atom, forming an Si-O-B bond angle of 168.4 (4)
      degrees. The steric and electronic effects of the Zr atom and the borate moieties
      force the silsesquioxane core to distort. These distortions can be seen by
      examination of the Si-O-Si bond angles.

PMID- 15237162
TI  - Hemi[hexaaquamagnesium(II)] (mu-2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4
      chlorophenolato)bis[diaquamagnesium(II)] decahydrate.
AB  - The crystal structure of the title compound,
      [Mg(H2O)6]0.5[Mg2(C16H14ClN2O9)(H2O)4].10H2O, shows that this binuclear complex
      consists of two Mg centres in distorted octahedral geometry, joined by an oxo
      bridge which is a derivative of the deprotoned hydroxy group of the phenolate in
      the ligand molecule. In the anion, the coordination sphere of each MgII ion is
      completed by two carboxylates, a tertiary N atom and two water molecules. The
      inner coordination spheres for the MgII ions are very similar, both in ligand
      sets and in geometry. Each unit of the binuclear complex has one negative charge
      neutralized by a neighbouring hydrated cation, [Mg(H2O)6]2+, in which the Mg atom
      lies on an inversion centre. In each cell, there are 34 water molecules and most
      of them participate in the formation of hydrogen bonds, which contribute greatly
      to the stability of the whole structure.

PMID- 15237163
TI  - 4,4,6,6-Tetrachloro-2,2-(ethylenedioxydi-o-phenylenediimino)
      2lambda5,4lambda5,6lambda5-cyclotriphosphazene.
AB  - The title ligand, C14H14Cl4N5O2P3, is a cyclophosphazene lariat (PNP pivot) ether
      with a spiro-cyclic 11-membered macrocyclic ring containing two ether O and two N
      atoms; the phosphazene ring is nearly planar. The macrocyclic ring contains a
      four-centred (trifurcate) N-H...O/N-H...N hydrogen bond, and the relative inner
      hole size of the macrocycle is approximately 1.14 A in radius. The molecules are
      linked about inversion centres by N-H...N hydrogen bonds into centrosymmetric
      dimers.

PMID- 15237164
TI  - 1-[(4-Chlorobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide sesquihydrate
      and 1-[(4-bromobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide
      sesquihydrate.
AB  - The title compounds, C15H16ClN2O+.Br-.1.5H2O and C15H16BrN2O+.Br-.1.5H2O, are
      isomorphous. The benzene ring is oriented nearly normal to the pyridine ring in
      both compounds. The molecular packing is mainly influenced by intermolecular O
      H...O and O-H...Br interactions, as well as weak intramolecular C-H...O
      interactions. The H2OBr- units form an extended water-bromide chain, with a
      bridging water molecule on a twofold axis.

PMID- 15237166
TI  - 2-Aminopyridinium-fumarate-fumaric acid (2/1/1).
AB  - The title complex, 2C5H7N2+.C4H2O42-.C4H4O4, contains cyclic eight-membered
      hydrogen-bonded rings involving 2-aminopyridinium and fumarate ions. The fumaric
      acid molecules and fumarate ions lie on inversion centers and are linked into
      zigzag chains by O-H...O hydrogen bonds. The dihedral angle between the
      pyridinium ring and the hydrogen-bonded fumarate ion is 7.60 (4) degrees. The
      fumarate anion is linked to the pyridinium cations by intermolecular N-H...O
      hydrogen bonds. The heterocycle is fully protonated, thus enabling amine-imine
      tautomerization.

PMID- 15237165
TI  - 3,6-Dihydroxy-2-(11-phenylundecanoyl)cyclohex-2-en-1-one from Virola venosa bark.
AB  - The structure of the title compound, C23H32O4, an arylalkanone isolated from the
      petroleum ether fraction of the ethanol extract of the bark of Virola venosa, has
      been established by NMR spectroscopy and, for the first time, by X-ray structure
      analysis. Two independent molecules of the same enantiomer are present in the
      unit cell. Both molecules exhibit an intramolecular hydrogen bond, which can be
      correlated with a rare signal observed at 18.28 p.p.m. in the 1H NMR spectrum.
      The packing, in space group P1, is determined by a pseudo-center of symmetry
      leading to a short intermolecular contact, which is present in one molecule but
      does not occur in the other. As a consequence, the O-C-C-O torsion angles [-16.9
      (3) and -12.7 (3) degrees ] through the ketone and its adjacent hydroxy group are
      significantly different in the two molecules.

PMID- 15237167
TI  - A new photochromic tetrahydroindolizine.
AB  - The title compound, dimethyl 10b'-(4-fluorostyryl)-8',9'-dimethoxy-4-nitro-5',6'
      dihydrospiro[9H-fluorene-9,1'(10b'H)-pyrrolo[2,1-a]isoquinoline]-2',3'
      dicarboxylate, C38H31FN2O8, is a new photochromic tetrahydroindolizine. One of
      the C-C bonds at the spiro C atom is very long [1.630 (2) A], thus explaining the
      photochromic behaviour.

PMID- 15237168
TI  - Partially oxidized [2-[(benzoylmethylene)diphenyl-lambda5
      phosphino]ethyl]diphenylphosphine as a monohydrate.
AB  - The title compound is a co-crystal of [2-[(benzoylmethylene)diphenyl-lambda5
      phosphino]ethyl]diphenylphosphine oxide, [2-[(benzoylmethylene)diphenyl-lambda5
      phosphino]ethyl]diphenylphosphine and water in an approximate 2:1:3 ratio, with
      an overall composition of C34H30O1.678P2.H2O. The ylidic portion shows the
      expected electronic polarization, and the organic components are linked by a
      combination of C-H...O and C-H...pi(arene) hydrogen bonds.

PMID- 15237169
TI  - 3-tert-Butyl-7,7-dimethyl-1-phenyl-5,6,7,8-tetrahydroimidazo[3,4-b]quinolin-5-one
      and 2,8,8-trimethyl-5-phenyl-6,7,8,9-tetrahydroimidazo[2,3-a]quinolin-6-one:
      chains generated by C-H...N hydrogen bonds.
AB  - In both 3-tert-butyl-7,7-dimethyl-1-phenyl-5,6,7,8-tetrahydroimidazo[3,4
      b]quinolin-5-one, C22H25N3O, (I), and 2,8,8-trimethyl-5-phenyl-6,7,8,9
      tetrahydroimidazo[2,3-a]quinolin-6-one, C19H19N3O, (II), the heterobicyclic
      portions of the molecules are planar, with naphthalene-type delocalization in
      (II), while the carbocyclic ring in each compound adopts an envelope
      conformation. In both (I) and (II), the molecules are linked weakly into chains
      by a single C-H...N hydrogen bond.

PMID- 15237170
TI  - S-ethyl N-benzoyldithiocarbamate: two independent hydrogen-bonded R(2)2(8) dimers
      of different symmetry linked into chains by a C-H...pi(arene) interaction.
AB  - The title compound, C10H11NOS2, crystallizes with Z' = 2 in space group C2/c. The
      molecules are linked by two N-H...S hydrogen bonds [H...S = 2.60 and 2.62 A,
      N...S = 3.350 (2) and 3.490 (2) A, and N-H...S = 143 and 172 degrees] into two
      distinct types of R(2)2(8) dimer, viz. one generated by inversion and the other
      by a twofold rotation axis. A single C-H...pi(arene) hydrogen bond links the two
      types of dimer into chains.

PMID- 15237171
TI  - rac-3-(5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylthiazolidin-4-one:
      sheets built from N-H...N and C-H...pi(arene) hydrogen bonds.
AB  - The title compound, C19H18N4OS, crystallizes in space group P1 with Z' = 2. The
      two molecules in the selected asymmetric unit are nearly enantiomorphous. The
      molecules are linked by two N-H...N hydrogen bonds [H...N both 2.20 A, N...N =
      3.064 (3) and 3.077 (3) A, and N-H...N = 165 and 172 degrees] into C(2)2(10)
      chains, and these chains are linked into sheets by two independent C
      H...pi(arene) hydrogen bonds.

PMID- 15237172
TI  - 7-Deaza-2'-deoxy-7-propynylguanosine.
AB  - The title compound, C14H16N4O4, adopts the anti conformation at the glycosylic
      bond [chi -117.1 (5) degrees]. The sugar pucker of the 2'-deoxyribofuranosyl
      moiety is C2'-endo-C3'-exo, 2T3 (S-type). The orientation of the exocyclic C4'
      C5' bond is +sc (gauche). The propynyl group is linear and coplanar with the
      nucleobase moiety. The structure of the compound is stabilized by several
      hydrogen bonds (N-H...O and O-H...O), leading to the formation of a multi-layered
      network. The nucleobases, as well as the propynyl groups, are stacked. This
      stacking might cause the extraordinary stability of DNA duplexes containing this
      compound.

PMID- 15237173
TI  - 2-Benzoyl-N-phenyl-2-(1,2,4-triazol-1-yl)thioacetamide and 2-(4-methoxybenzoyl)-N
      phenyl-2-(1,2,4-triazol-1-yl)thioacetamide.
AB  - In the two title compounds, C17H14N4OS, (I), and C18H16N4O2S, (II), the dihedral
      angles between the planes of the triazole and N-phenyl rings and the plane of
      five of the atoms that link these two rings are 63.5 (8) and 73.2 (6) degrees for
      (I), and 65.1 (1) and 72.1 (3) degrees for (II), respectively. There are some
      inter- and intramolecular interactions in the crystal structure.

PMID- 15237174
TI  - (R)-4-(4-fluorophenyl)-1-[2-hydroxy-2-(3-methyl-1-benzofuran-2
      yl)ethyl]piperazinium chloride propan-1-ol solvate.
AB  - The title compound, C21H24FN2O2+.Cl-.C3H8O, is a potential drug designed as a
      hybrid compound with antihypertensive, antioxidant and beta-adrenolytic activity.
      The cation contains nearly planar benzofuran and fluorophenyl ring systems, as
      well as a piperazine ring adopting an almost perfect chair conformation. The
      benzofuran and piperazine moieties are connected by an ethyl chain, the moieties
      forming a dihedral angle of 163.12 (13) degrees. In the crystal structure, ions
      and propanol solvent molecules are linked via N-H...Cl and O-H...Cl bonds into
      linear (010) chains.

PMID- 15237175
TI  - 5-Benzoylamino-3-bromo-4-(4-methoxyphenyl)-4,5-dihydroisoxazole-5-carboxylic
      acid.
AB  - The title compound, C18H15BrN2O5, a promising N-protected alpha-amino acid, was
      synthesized directly from an unusual bromo dipole and a 4
      (arylmethylene)oxazolone. The crystal packing of the title compound is a racemic
      mixture. Peculiar graph-set motifs driven by the most important hydrogen bonds
      are described.

PMID- 15237176
TI  - 2,6-Dimethyl-4-(phenyldiazenyl)phenol.
AB  - The crystal structure of the title compound, C14H14N2O, determined at 293 K,
      shows that the molecule is approximately planar in the solid state and that the
      aromatic rings have a trans configuration with respect to the azo double bond, as
      found for other diazene derivatives. The packing can be described as a polymeric
      arrangement of molecules linked through O-H...N and C-H...O hydrogen bonds and
      close contacts. These intermolecular interactions result in the formation of
      infinite chains parallel to the b axis.

PMID- 15237177
TI  - 2'-Amino-3-methoxypyrimidino[5',4':16,17]estra-1,3,5(10),16-tetraene.
AB  - In the title compound, C21H25N3O, the six-membered ring that is fused to two
      other six-membered rings in the estrane moiety adopts an envelope conformation.
      The compound shows intermolecular hydrogen bonding of the amine group to an N
      atom of the pyrimidine moiety, as well as weak intermolecular interactions
      involving H atoms in the hydrophobic residue of the molecule.

PMID- 15237178
TI  - rac-Eudesm-7(11)-en-4-ol.
AB  - The isolation and structural determination of rac-eudesm-7(11)-en-4-ol, C15H26O,
      from the steam distillate of the flowers of Dipterocarpus cornutus Dyer
      (Dipterocarpaceae) is described. The structure was determined from spectroscopic
      data and a single-crystal X-ray study. Two similar independent molecules comprise
      the asymmetric unit of the structure.

PMID- 15237179
TI  - 3-Bromomethyl-3-ethyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazine-1,4
      dione.
AB  - In the title compound, C10H14BrNO3, the six-membered lactone ring is in a boat
      conformation, with the two carbonyl groups cis to one another across the boat
      basal plane. C-H...O hydrogen bonds and weak C-H...Br interactions stabilize the
      crystal structure.

PMID- 15237180
TI  - N,N'-bis[1-(pyrazin-2-yl)ethylidene]hydrazine.
AB  - Molecules of the title compound, C12H12N6, contain both a diimine linkage and an
      N-N bond, and assume a planar structure. The compound lies about an inversion
      centre and there are three intramolecular C-H...N hydrogen bonds.

PMID- 15237181
TI  - (Benzofuran-2-yl)(3-methyl-3-phenylcyclobutyl)methanone.
AB  - The structure of the title compound, C20H18O2, consists of a dimeric arrangement
      of benzofuran molecules around an inversion centre, linked via C-H...O hydrogen
      bonds. There are also C-H...pi ring interactions. All these interactions result
      in the formation of infinite chains parallel to the [100] axis. The cyclobutane
      ring is puckered, with a dihedral angle of 29.03 (13) degrees between the two
      three-atom planes.

PMID- 15237182
TI  - N-(4-fluorophenyl)-4-nitrophthalimide: tripartite hydrogen-bonded sheets.
AB  - Molecules of the title compound, C14H7FN2O4, are linked by two C-H...O hydrogen
      bonds [H...O = 2.42 and 2.44 A, C...O = 3.173 (9) and 3.313 (10) A, and C-H...O =
      134 and 157 degrees] into deep tripartite sheets, where the central layer is
      built from hydrogen-bonded R(6)6(24) rings and where the F atoms all lie on the
      exterior surfaces of the sheets.

PMID- 15237183
TI  - 2,6-Dibenzyl-1,2,3,5,6,7-hexahydro-2,4,6,8-tetraaza-s-indacene and 2,6-bis(4
      methoxybenzyl)-1,2,3,5,6,7-hexahydro-2,4,6,8-tetraaza-s-indacene.
AB  - The title compounds, C22H22N4 and C24H26N4O2 [alternative names: 2,6-dibenzyl
      2,3,6,7-tetrahydro-1H,5H-dipyrrolo[3,4-b; 3',4'-e]pyrazine and 2,6-bis(4
      methoxybenzyl)-2,3,6,7-tetrahydro-1H,5H-dipyrolo[3,4-b;3',4'-e]pyrazine], two
      1,2,3,5,6,7-hexahydro-2,4,6,8-tetraaza-s-indacene derivatives, are both
      centrosymmetric and have similar S-shaped structures. In the former, there are
      two independent molecules (A and B), both of which possess Ci symmetry. These two
      molecules are arranged such that the benzene ring substituent of molecule B is
      directed towards the plane of the benzene ring substituent of molecule A, with a
      dihedral angle of 55.4 (2) degrees between their planes. The shortest C-H...C
      distance is, however, only 3.21 (1) A. In both compounds, the benzene ring
      substituents are almost perpendicular to the plane of the central pyrazine ring,
      and the pyrrolidine rings have perfect envelope conformations. In the crystal
      structures of both compounds, the molecules pack in a herring-bone arrangement.

PMID- 15237184
TI  - Ethyl (E)-3-(2-hydroxyphenyl)-2-(morpholinocarbonyl)propenoate.
AB  - The title compound, C16H19NO5, crystallizes as a centrosymmetric dimer through
      strong O-H...O hydrogen-bonding interactions between the hydroxyphenyl and
      morpholinocarbonyl groups. The morpholinocarbonyl group is almost perpendicular
      to the propenoate moiety. Electron delocalization in the N-C(=O) fragment leads
      to the formation of hydrogen-bonded S(5) ring motifs through C-H...O
      interactions.

PMID- 15237185
TI  - Difurazano[3,4-b:3',4'-f]-4,5-diaza-1,8-dioxacyclododecine and an acyclic
      analogue.
AB  - The novel title furazan-containing macrocycle (systematic name: 6,9,14,17
      tetraoxa-2,3,5,7,16,18-hexaazatricyclo[13.3.0.0(4,8)]octadeca-4,7,15,18
      tetraene), C8H10N6O4, (I), is the first macrocycle where the furazan rings are
      connected via a hydrazine group. In spite of the strain in the 12-membered
      macrocycle of (I), the geometry of the furazan fragment is the same in (I) and in
      its acyclic analogue 1,8-bis(5-aminofurazan-4-yloxy)-3,6-dioxaoctane, C10H16N6O6,
      (II). In both compounds, the participation of the furazan rings in intermolecular
      hydrogen bonding equalizes the N-O bonds within the furazan rings, in contrast
      with rings which do not participate in such interactions.

PMID- 15237186
TI  - 1,2-Bis(methylsulfanyl)-1,2-dicarba-closo-dodecaborane(12).
AB  - In the title compound, 1,2-(SCH3)2-1,2-closo-C2B10H10 or C4H16B10S2, the
      methylsulfanyl groups are bonded to the C atoms of the 1,2-dicarba-closo
      dodecaborane cage. The Ccage-Ccage distance is 1.8033 (18) A and the S-Ccage
      Ccage-S torsion angle is 1.07 (13) degrees. The Ccage-Ccage distance is compared
      with those in other 1,2-dicarba-closo-dodecaborane derivatives.

PMID- 15237187
TI  - Conformational switching caused by biphenyl substitution at the Calpha position:
      ethyl 2-benzyl-2-(formylamino)-3-phenylpropionate and ethyl 3-(1,1'-biphenyl-4
      yl)-2-(formylamino)-2-(4-phenylbenzyl)propionate.
AB  - The title compounds, C19H21NO3 and C31H29NO3, are derivatives of alpha
      aminoisobutyric acid, with benzyl and dibenzyl substitution. The pseudo-peptide
      formed by the N-formyl and ethyl ester substitution at the Calpha position
      switches from a trans-trans to a trans-cis configuration as a result of biphenyl
      substitution. The packing of the compounds is stabilized by N-H...O and C-H...O
      hydrogen bonds.

PMID- 15237188
TI  - Triphenylphosphine oxide-1-naphthoic acid (1/1).
AB  - In the title compound, C18H15OP.C11H8O2, co-crystallization of triphenylphosphine
      oxide with 1-naphthoic acid yields a supramolecular structure held together by
      one O-H...O and three C-H...O hydrogen bonds. The O-H...O hydrogen bond [O...O =
      2.592 (2) A] has little effect on the O=P bond distance.

PMID- 15237189
TI  - (5,11,17,23-Tetra-tert-butyl-26,28-dihydroxycalix[4]arene-25,27-dioxy)diacetic
      acid N,N-dimethylformamide trisolvate.
AB  - The title compound, C48H60O8.3C3H7NO, is a derivative of calix[4]arene in the
      cone conformation, modified with distal carboxylic acid functional groups at the
      lower rim. A clathrate dimethylformamide (DMF) molecule is located within the
      calix[4]arene cone, and two DMF solvate molecules participate in hydrogen bonding
      with the carboxylic acid groups. Intramolecular hydrogen bonds are also formed
      between the OH groups and the adjacent ether groups in the partially substituted
      calix[4]arene.

PMID- 15237190
TI  - 1-Chloro-3,6-dimethoxy-2,5-dimethylbenzene and 1-chloro-3,6-dimethoxy-2,4
      dimethylbenzene.
AB  - The title compounds, 1-chloro-3,6-dimethoxy-2,5-dimethylbenzene, (IIIa), and 1
      chloro-3,6-dimethoxy-2,4-dimethylbenzene, (IIIb), both C10H13ClO2, were obtained
      from 2,5- and 2,6-dimethyl-1,4-benzoquinone, respectively, and are intermediates
      in the synthesis of ammonium quinone derivatives. The isomers have different
      substituents around the methoxy groups and crystallize in different space groups.
      In both molecules, the methoxy groups each have different orientations with
      respect to the benzene ring. In both cases, one methoxy group lies in the plane
      of the ring and can participate in conjugation with the aromatic system, while
      the second is almost perpendicular to the plane of the aromatic ring. The C-O-C
      bond angles around these substituents are also different: 117.5 (4) and 118.2 (3)
      degrees in (IIIa) and (IIIb), respectively, when the methoxy groups lie in the
      plane of the ring, and 114.7 (3) and 113.6 (3) degrees in (IIIa) and (IIIb),
      respectively, when they are out of the plane of the ring.

PMID- 15237191
TI  - The primitive streak, the caudal eminence and related structures in staged human
      embryos.
AB  - The caudal region of the trunk was reassessed in 52 serially sectioned human
      embryos of stages 8-23, 42 of which were controlled by precise graphic
      reconstructions. The following observations, new for the human, are presented.
      (1) The neurenteric canal is an important landmark because rostral to it the
      neural plate of stages 8, 9, and the main part of the notochord develop, whereas
      caudal to it the neural plate of stages 10-12 and the caudal portion of the
      notochord are formed. All somites at stages 9-11 and probably also at stage 12
      arise rostral to the site of the neurenteric canal. (2) A 'chordoneural hinge'
      can be detected in stages 10 and 11, where the caudal part of the neural plate
      gives off cells that probably participate in the production of mesenchyme. (3)
      When apparent disappearance of the epiblast is used as a criterion, then the
      primitive streak seems to end during stage 9. (4) The caudal eminence, derived
      from the primitive streak and covered by ectoderm, forms at stage 10 caudal to
      the site of the former neurenteric canal and persists as a terminal cap to at
      least stage 14, although formation of mesenchyme continues in stages 15 to 17 or
      18. (5) As the region rostral to the site of the neurenteric canal grows because
      of the development of somites, the caudal eminence is shifted caudally. (6) The
      caudal eminence is most active developmentally during stage 13, when most of the
      required (ca 6 out of 9) pairs of somites appear. (7) The eminence produces the
      caudal part of the notochord and, after closure of the caudal neuropore, all
      caudal structures, but it does not produce even a temporary 'tail' in the human.
      (8) A temporal overlap results between primary and secondary development in the
      caudal part of the notochord. (9) Primary development begins very early with the
      formation of the inner cell mass at stage 3, and includes the development of the
      somites rostral to the neurenteric canal, whereas secondary development, with the
      exception of the notochord caudally, commences at stage 12. (10) Primary
      neurulation lasts from stage 8 to stage 12, secondary from stage 12 to stages 17
      or 18. (11) Secondary development and secondary neurulation are characterized
      morphologically by direct formation of structures (notochord, postcloacal gut,
      neural cord/neural tube) from mesenchyme.

PMID- 15237193
TI  - Collagen type I prevents glyoxal-induced apoptosis in osteoblastic cells cultured
      on titanium alloy.
AB  - Advanced glycation end products (AGEs) irreversibly cross-link proteins with
      sugars and accumulate at a higher age and in diabetes, processes which can
      interfere with the integration of implants into the tissue. Glyoxal is a highly
      reactive glycating agent involved in the formation of AGEs and is known to induce
      apoptosis, as revealed by the upregulation of caspase-3 and fractin (caspase-3
      being a key enzyme activated during the late stage of apoptosis and fractin being
      a caspase-cleaved actin fragment). In this study, we investigated the influence
      of collagen type I coating on the cytotoxic effect of glyoxal on rat calvarial
      osteoblastic cells and on human osteosarcoma cells (Saos-2) grown on titanium
      alloy, Ti6Al4V. Activation of caspase-3 and fractin was measured by counting
      immunohistochemically stained cells and by flow cytometry with propidium iodide
      (detection of the apoptosis indicating a sub-G1 peak). Our results showed an
      increased number of apoptotic osteoblasts after incubation with glyoxal on
      Ti6Al4V discs. However, the number of apoptotic cells on collagen-coated titanium
      was significantly smaller than on uncoated titanium after the same treatment. The
      present findings demonstrate that osteoblasts treated with glyoxal undergo
      apoptosis, whereas collagen type I coating of titanium alloys (used for implants)
      has an antiapoptotic function.

PMID- 15237192
TI  - Development of thyroid-stimulating hormone beta subunit-producing cells in the
      chicken embryonic pituitary gland.
AB  - In previous studies, the distribution of thyrotropes in the chicken pituitary
      gland has been analyzed by immunohistochemistry using heterologous antibodies. In
      this study, we examined the distribution of thyroid-stimulating hormone beta
      subunit-immunopositive (TSHbeta-ip) cells and the expression of TSHbeta mRNA in
      the pituitary glands of chicken embryos by immunohistochemistry using a specific
      antiserum to the chicken TSHbeta, in situ hybridization and RT-PCR.
      Immunohistochemical and morphometric analyses revealed that the TSHbeta-ip cells
      first appeared on embryonic day 10 (E10) in the pituitary gland and were mainly
      distributed in the cephalic lobe and that the cell density on E20 was almost 4
      times greater than that on E10. The chicken TSHbeta-ip cells could be classified
      into two types based on morphological characteristics: round-shaped cells and
      club-shaped cells, which have long cytoplasmic processes. In situ hybridization
      analysis revealed that TSHbeta mRNA-expressing cells were expressed from E9 in
      the cephalic lobe and that the extent of TSHbeta mRNA-expressing cells coincided
      with that of TSHbeta-ip cells. RT-PCR also showed that TSHbeta mRNA was expressed
      from E9 and that Pit-1 mRNA was expressed from E5. These results clearly
      demonstrated that the expression of chicken TSHbeta mRNA starts on E9, that
      TSHbeta-ip cells appear on E10, mainly in the cephalic lobe, and that TSHbeta-ip
      cells can be classified into two cell types (round- and club-shaped cells).

PMID- 15237194
TI  - Establishment and characterization of a human gastric carcinoma cell line TMC-1.
AB  - Established cancer cell lines are useful in the study of various cancers. We
      established a human gastric carcinoma cell line TMC-1 derived from the lymph node
      of a moderately differentiated adenocarcinoma of the stomach. TMC-1 cells grew in
      vitro as a mixture of attached and suspension cells, and exhibited spindle or
      ovoid morphology. They had a population doubling time of 15 h, a plating
      efficiency of 61%, formed colonies in semisolid agar, secreted the tumor marker
      CA 19-9, and were tumorigenic in athymic nude mice. The cells expressed E
      cadherin and beta-catenin. The karyotypic analysis demonstrated hyperdiploid
      features with a modal chromosome of 53. The cell had the deletion at chromosome
      18q and gains at chromosome 2p13-25, 5p15, 5q21-35, 7, 8q24, 9q, 11, 12p, 14q24
      32 and 20. Analysis by fluorescence in situ hybridization showed the deletion at
      7qtel and duplication at 7q11.2 at the rearranged chromosome 7. Growth of TMC-1
      cells was inhibited by 27-32% by interferon-alpha (2,000 U/ml) and by interferon
      gamma with an IC50 of 125 U/ml. The cell line is tumorigenic in vivo, and its
      growth is moderately inhibited by interferon-alpha and interferon-gamma. It can
      be used to develop new modalities of human gastric cancer treatment.

PMID- 15237195
TI  - General innervation pattern and sensory corpuscles in the scapholunate
      interosseous ligament.
AB  - The scapholunate interosseous ligament (SLIL) is biomechanically important in
      maintaining wrist motion and grip strength in the hand, but its possible sensory
      role in the dynamic muscular stability of the wrist joint has not been examined.
      The aim of this study was to use immunohistochemical methods to analyze the
      general innervation and the possible existence of sensory corpuscles in the SLIL.
      The ligament was excised in its entirety from 9 patients. Antibodies against the
      low-affinity p75 neurotrophic receptor (p75) were used to reveal sensory
      corpuscles as well as general innervation. Furthermore, antibodies against the
      general nerve marker protein gene product 9.5 (PGP 9.5) and the glial marker S
      100 were used to additionally depict innervation and corpuscular structures.
      Blood vessels occurred in areas interspersed throughout the homogeneous
      collagenous structure. In these vascularized areas, the SLIL was found to be
      supplied with nerve fascicles and sensory corpuscles of both the Ruffini and
      lamellated type. p75 immunoreactivity (IR) was detected in association with the
      nerve fascicles and the corpuscles, particularly in their capsule. S-100 IR was
      found in the Schwann cells in the central regions of the corpuscle, and PGP 9.5
      IR marked the axonal structures in the corpuscles. New information on
      neurotrophin receptor distribution in ligaments has been obtained here. The
      presence of nerve fascicles and particularly sensory corpuscles in the SLIL
      suggests that the ligament has a proprioceptive role in the stability of the
      wrist. The marked p75 IR further indicates that neurotrophins play a part in a
      proprioceptive system in the ligament, given the importance of neurotrophins in
      maintaining sensory function.

PMID- 15237196
TI  - Progress in understanding GJB2-linked deafness.
AB  - Mutations in the GJB2 gene (encoding for Connexin 26 protein) represent a leading
      cause of genetic hearing impairment. Extensive epidemiological and molecular
      studies have been reported, describing GJB2 mutations type, frequency and
      distribution. Moreover, several aspects of GJB2 mutations pathogenic effects have
      been elucidated taking advantage of in vitro and in vivo experimental approaches.
      Progress through reported studies is reviewed, highlighting recent major
      achievements in this field. Attention is focused on different unresolved
      questions regarding GJB2 deafness pathogenesis and genotype-phenotype
      relationships. Clarification of these important clues will significantly increase
      our understanding of the molecular basis of hearing loss and will improve the
      effectiveness of diagnosis and counselling of this frequent disease.

PMID- 15237197
TI  - Ethical aspects of genetic testing in the workplace.
AB  - The European Group on Ethics and New Technologies, which advises the European
      Commission, has published an opinion paper on ethical aspects of genetic testing
      in the workplace. The paper goes well beyond the usual ethical issues, presenting
      a summary of genetic testing in the workplace in the United States and Europe and
      criteria for appropriate testing. Unlike many other documents on ethics, it pays
      close attention to the problem of false-positive and false-negative test results.
      Although no genetic tests are currently appropriate for screening workers or
      applicants for jobs in which occupational hazards exist, inappropriate testing
      has occurred and regulations are needed to ensure that only appropriate testing
      is used in the future. Workers or their representatives should be involved in
      deciding when and how genetic testing in the workplace is done.

PMID- 15237198
TI  - Public attitudes to human gene therapy: a pilot study in Wales.
AB  - OBJECTIVE: This study aimed to explore some factors influencing perceptions of
      human gene therapy. METHOD: A small qualitative study using two semi-structured
      interviews per participant (n = 22). The groups comprised (1) people with cystic
      fibrosis and members of their family (n = 9), and (2) students from a science
      evening class as well as lay members of the public selected from the practice
      list of a local general practitioner (n = 13). RESULTS: This pilot study
      demonstrates support for somatic gene therapy and ambivalence about germline gene
      therapy. A clear distinction is drawn between therapy and enhancement, with the
      majority opposing gene enhancement. CONCLUSIONS: Attitudes towards the
      acceptability of gene therapy are not necessarily determined by experience of, or
      exposure to, a genetic condition. More research is needed with the general public
      to determine what is perceived to be acceptable public policy in this field.

PMID- 15237199
TI  - Awareness of genetic testing for increased cancer risk in the year 2000 National
      Health Interview Survey.
AB  - OBJECTIVES: This study explores factors associated with differential awareness of
      genetic tests for increased cancer risk in the US. METHODS: 27,405 respondents
      from the 2000 National Health Interview Survey, ages 25+, were asked if they had
      heard of these tests. RESULTS: 44.4% said 'yes', including 49.9% of whites, 32.9%
      of African-Americans, 32.3% of American Indians/Alaskan Natives, 28.0% of
      Asian/Pacific Islanders, and 20.6% of Hispanics. In multivariate analysis, test
      awareness was significantly associated with higher education, white race, age <60
      years, female gender, private health insurance, personal or parent's history of
      certain cancers, physical activity, and vitamin/supplement use, among other
      factors. CONCLUSIONS: The survey showed which population subgroups may lack
      access to cancer genetics information and may therefore benefit from targeted
      strategies to ensure risk-appropriate utilization of genetic counseling and
      testing.

PMID- 15237200
TI  - How should preconceptional cystic fibrosis carrier screening be provided?
      Opinions of potential providers and the target population.
AB  - BACKGROUND: Since the identification of the cystic fibrosis (CF) gene, large
      scale CF carrier screening has become possible. One possible target group is
      couples planning a pregnancy (preconceptional screening), providing a maximum
      number of reproductive options and a minimum of time constraints. OBJECTIVES: To
      identify obstacles in the implementation of a preconceptional CF carrier
      screening programme, to find out how potential providers and the target
      population think the screening should be implemented, and to determine whether
      potential providers think they are able to provide the screening programme.
      METHODS: A survey was conducted among 200 general practitioners (GPs), 134
      Municipal Health Service (MHS) workers and 303 recently married couples. RESULTS:
      52% (102/197) of the eligible GPs participated, 84% (113/134) of the MHS workers
      and 70% (380/544) of the individuals planning a pregnancy. In general, potential
      providers and the target population had a positive attitude towards CF screening.
      Preferred methods of informing the target population were: in leaflets, during a
      GP consultation for those people seeking advice before pregnancy, and sending a
      personal invitation to all people of reproductive age. Potential providers
      believed that they would be able to provide the screening programme. Important
      perceived obstacles were the absence of a preconceptional care setting, high
      workload, and lack of financial resources. CONCLUSION: Different intervention
      strategies will be necessary to overcome the obstacles in the implementation. The
      positive attitude towards CF carrier screening in combination with the
      willingness of the potential providers to participate in the screening programme
      will make it easier to overcome the obstacles.

PMID- 15237201
TI  - The Cancer Genetics Network: recruitment results and pilot studies.
AB  - OBJECTIVE: The National Cancer Institute established the Cancer Genetics Network
      (CGN) to support collaborative investigations into the genetic basis of cancer
      susceptibility, explore mechanisms to integrate this new knowledge into medical
      practice, and identify ways of addressing the associated psychosocial, ethical,
      legal, and public health issues. SUBJECTS AND METHODS: The CGN has developed the
      complex infrastructure required to support the projects, including the
      establishment of guidelines and policies, uniform methods, standard
      questionnaires to be used by all of the centers, and a standard format for
      submission of data to the Informatics Center. Cancer patients and their family
      members have been invited to enroll and be included in a pool of potential study
      participants. The Information Technology Group is responsible for support of the
      design, implementation, and maintenance of the multicenter Network-wide research
      protocols. RESULTS: As of January 2004, the CGN contained data on 23,995 probands
      (participants) and 425,798 family members. As a resource for cancer genetic
      studies, the CGN has a large number of probands and first-degree relatives with
      and without cancer and with multiple ethnicities. Different study designs can be
      used including case-control, case-case, and family studies. CONCLUSIONS: The
      unique resources of the CGN are available for studies on cancer genetic
      susceptibility, translational research, and behavioral research. The CGN is now
      at a point where approved collaborators may have access to enrolled patients and
      their families for special studies, as well as to the clinical, environmental and
      family cancer history data banked in the Informatics Center.

PMID- 15237202
TI  - Benefit sharing in smaller markets: the case of Newfoundland and Labrador.
AB  - This case report describes recent efforts in the Canadian province of
      Newfoundland and Labrador to establish an appropriate benefit-sharing model for
      human genetic research conducted there. The relatively homogeneous population of
      this island province has proven to be attractive to the drug development
      industry. However, unlike large-scale national projects that include broad
      benefit-sharing arrangements from the outset such as those proposed for places
      like Iceland and Estonia, there are no plans in Newfoundland and Labrador to
      establish a large gene bank. Hence a benefit-sharing protocol that will assess
      individual genetic studies on a case by case basis has been proposed. The
      province is moving toward legislation to establish a Provincial Health Research
      Ethics Board (PHREB) that will ensure that all human health research conducted in
      the province receives local ethics review. The proposed benefit-sharing protocol
      calls for the establishment of a Standing Committee on Human Genetic Research
      (SCHGR) that will operate in concert with the PHREB and will ensure that research
      sponsors enter into appropriate benefit-sharing arrangements with the province.

PMID- 15237203
TI  - Genetic counsellors: a registration system to assure competence in practice in
      the United kingdom.

PMID- 15237204
TI  - The mouse "tool box" for meiotic studies.
AB  - Besides availability, there are numerous advantages to using mice for meiotic
      studies: (1) techniques exist for enriching the population of spermatocytes at
      particular meiotic stages; (2) spermatogenesis in mice is highly synchronized and
      testis sections afford a highly accurate method of staging meiotic events; (3)
      knock-out mice provide a rich source of meiotic mutants. Coupled with antibody
      localization techniques these tools, singularly and in combination, provide
      multiple means of temporally and physically dissecting meiosis.

PMID- 15237205
TI  - The initiation of homologous chromosome synapsis in mouse fetal oocytes is not
      directly driven by centromere and telomere clustering in the bouquet.
AB  - We investigated the behaviour of centromeres and distal telomeres during the
      initial phases of female meiosis in mice. In particular, we wished to determine
      whether clustering of centromeres and telomeres (bouquet formation) played the
      same crucial role in homologous chromosome pairing in female meiosis as it does
      in the male. We found that synapsis (intimate homologous chromosome pairing) is
      most frequently initiated in the interstitial regions of homologous chromosomes,
      apparently ahead of the distal regions. The proximal ends of the chromosomes
      appear to be disfavoured for synaptic initiation. Moreover, initiation of
      synapsis occurred in oocytes that showed little or no evidence of bouquet
      formation. A bouquet was present in a substantial proportion of cells at mid to
      late zygotene, and was still present in some pachytene oocytes. This pattern of
      bouquet formation and pairing initiation is in stark contrast to that previously
      described in the male mouse. We propose that although dynamic movements of
      centromeres and telomeres to form clusters may facilitate alignment of homologues
      or homologous chromosome segments during zygotene, in the female mouse positional
      control of synaptic initiation is dependent on some other mechanism.

PMID- 15237206
TI  - Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and
      SYCP2 align by homology but fail to synapse and have possible impaired
      specificity of chromatin loop attachment.
AB  - The targeted deletion of the meiotic chromosome core component MmSYCP3 results in
      chromosome synaptic failure at male meiotic prophase, extended meiotic
      chromosomes, male sterility, oocyte aneuploidy and absence of the MmSYCP2
      chromosome core component. To test the functions of SYCP2 and SYCP3 proteins in
      the cores, we determined the effect of their deletion on homology recognition by
      whole chromosome painting and the effect on chromatin loop attachment to the
      cores with endogenous and exogenous sequences. Because we observed that the
      alignment of cores is between homologs, it suggested that alignment is not a
      function of the chromosome core components but might be mediated by chromatin
      chromatin interactions. The alignment function therefore appears to be separate
      from intimate synapsis function of homologous cores that is observed to be
      defective in the SYCP3-/- males. To examine the functions of the SYCP2 and 3 core
      proteins in chromatin loop attachment, we measured the loop sizes of the
      centromeric major satellite chromatin and the organization of an exogenous
      transgene in SYCP3+/+ and SYCP3-/- males. We observed that these satellite
      chromatin loops have a normal appearance in SYCP3-/- males, but the loop
      regulation of a 2-Mb exogenous lambda phage insert appears to be altered.
      Normally the insert fails to attach to the core except by flanking endogenous
      sequences, but in the absence of SYCP2 and SYCP3, there appears to be multiple
      attachments to the core. This suggests that the selective preference for the
      attachment of mouse sequences to the chromosome core in the wild-type male is
      impaired in the SYCP3-/- male. Apparently the SYCP2 and SYCP3 proteins function
      in the specificity of chromatin attachment to the chromosome core.

PMID- 15237208
TI  - Male germline-specific histones in mouse and man.
AB  - In mice and humans, the production of male gametes is a result of a complex
      multistep process of stem cell differentiation. The final product, the mature
      spermatozoon, is designed for the safe delivery of a haploid copy of the paternal
      genetic information to the oocyte in a structural state suitable for zygote
      formation and embryogenesis. A remarkable structural reorganization of
      chromosomes in germline cells during mammalian spermatogenesis has been
      characterized. The most important steps are connected with the recombination
      events during meiosis and the final packaging of the haploid genome in the
      genetically inert, compacted nucleus of the sperm. Underlying the changes in
      chromatin organization is the appearance of testis-specific histones. Although
      the existence of such histones has been known for decades, their exact functions
      still are not established. Deciphering of the mouse and human genomes has allowed
      a more detailed description of the organization and regulation of the testis
      specific histone genes. In addition, it has facilitated the discovery of
      previously unknown proteins. This review summarizes contemporary information on
      these germline-specific/enriched histones in both the mouse and human and
      outlines early achievements in the identification of their functions.

PMID- 15237209
TI  - Single-cell quantitative RT-PCR analysis of Cpt1b and Cpt2 gene expression in
      mouse antral oocytes and in preimplantation embryos.
AB  - Fatty acids represent an important energy source for preimplantation embryos.
      Fatty acids oxidation is correlated with the embryo oxygen consumption which
      remains relatively constant up to the 8-cell stage, but suddenly increases
      between the 8-cell and morula stages. The degradation of fatty acids occurs in
      mitochondria and is catalyzed by several carnitine acyl transferases, including
      two carnitine palmitoyl transferases, CPT-I and CPT-II. We have carried out a
      study to determine the relative number of transcripts of Cpt1b and Cpt2 genes
      encoding for m-CPT-I and CPT-II enzymes, during mouse preimplantation
      development. Here we show that Cpt1b transcripts are first and temporally
      detected at the 2-cell stage and reappear at the morula and blastocyst stage.
      Cpt2 transcripts decrease following fertilization to undetectable levels and are
      present again later at the morula stage. These results show that transcription of
      both Cpt1b and Cpt2 is triggered at the morula stage, concomitantly with known
      increasing profiles of oxygen uptake and fatty acids oxidation. Based on the
      number of Cpt2 transcripts detected, we could discriminate the presence of two
      groups of embryos with high and low number of transcripts, from the zygote
      throughout preimplantation development. To further investigate if the
      establishment of these two groups of embryos occurs prior to fertilization, we
      have analyzed the relative number of transcripts of both genes in antral and
      ovulated MII oocytes. As for preimplantation embryos, MII oocytes show two groups
      of Cpt2 expression. Antral oocytes, classified according to their chromatin
      configuration in SN (surrounded nucleolus, in which the nucleolus is surrounded
      by a rim of Hoechst-positive chromatin) and NSN (not surrounded nucleolus, in
      which this rim is absent), show three groups with different numbers of Cpt2
      transcripts. All NSN oocytes have a number of Cpt2 transcripts doubled compared
      to that of the group of MII oocytes with high expression. Instead, SN oocytes
      could be singled out into two groups with high and low numbers of Cpt2
      transcripts, similar to those found in MII oocytes. The results of this study
      point out a correlation between the timing of fatty acids oxidation during
      preimplantation development and the expression of two genes encoding two enzymes
      involved in the oxidative pathway. Furthermore, although the biological meaning
      for the presence of two groups of oocytes/embryos with different levels of Cpt2
      transcripts remains unclear, the data obtained suggest a possible correlation
      between the levels of Cpt2 expression and embryo developmental competence.

PMID- 15237210
TI  - New mouse genetic models for human contraceptive development.
AB  - Genetic strategies for the post-genomic sequence age will be designed to provide
      information about gene function in a myriad of physiological processes. Here an
      ENU mutagenesis program (http://reprogenomics.jax.org) is described that is
      generating a large resource of mutant mouse models of infertility; male and
      female mutants with defects in a wide range of reproductive processes are being
      recovered. Identification of the genes responsible for these defects, and the
      pathways in which these genes function, will advance the fields of reproduction
      research and medicine. Importantly, this program has potential to reveal novel
      human contraceptive targets.

PMID- 15237207
TI  - Role of retinoid signaling in the regulation of spermatogenesis.
AB  - While the need for vitamin A for the normal progression of male germ cell
      differentiation has been known for many years, the molecular mechanisms
      underlying this requirement are poorly understood. This review will explore the
      aspects of the effects on spermatogenesis of dietary deprivation of vitamin A, in
      particular as to how they compare to the male sterility that results from the
      genetic ablation of function of the retinoid receptor RARalpha. The effects of
      other genes involved with retinoid synthesis, transport, and degradation are also
      considered. The possible cellular mechanisms that may be affected by the lack of
      retinoid signaling are discussed, in particular, cell cycle regulation and cell
      cell interaction, both of which are critical for normal spermatogenesis.

PMID- 15237211
TI  - Mouse zona pellucida genes and glycoproteins.
AB  - The zona pellucida (ZP) is a thick extracellular coat that surrounds all
      mammalian eggs. The ZP plays important roles during oogenesis, fertilization, and
      preimplantation development. The mouse ZP consists of only three glycoproteins,
      called ZP1, ZP2, and ZP3. All three glycoproteins are essential structural
      components of the ZP. Additionally, ZP3 serves as a primary sperm receptor and
      acrosome reaction-inducer, and ZP2 serves as a secondary sperm receptor during
      fertilization. ZP1, ZP2, and ZP3 are encoded by single-copy genes present on
      three different chromosomes. The genes are expressed exclusively by mouse oocytes
      as they grow and the cellular specificity can be ascribed to cis-acting sequences
      close to the site of transcription initiation and to certain trans-acting
      factors. Concomitantly, ZP polypeptides are synthesized, modified with N- and O
      linked oligosaccharides, secreted, and assembled into crosslinked filaments that
      exhibit a structural repeat. Nascent ZP glycoproteins are incorporated into large
      secretory vesicles that fuse with the oocyte plasma membrane and deposit nascent
      ZP glycoproteins into the innermost layer of the thickening ZP. Each ZP
      polypeptide possesses several characteristic features, including an N-terminal
      signal sequence, a ZP domain, a consensus furin cleavage site, and a C-terminal
      transmembrane domain. The latter is required for assembly of nascent ZP
      polypeptides into a ZP, cleavage at the consensus furin cleavage site is required
      for secretion, and the ZP domain supports protein:protein interactions during ZP
      assembly. At ovulation, when meiotic maturation of oocytes occurs and chromosomes
      condense into bivalents, expression of the three ZP genes ceases. Using "knockout
      mice", in the absence of either ZP2 or ZP3 expression, a ZP fails to assemble
      around growing oocytes and females are infertile. There is no effect on males. In
      the absence of ZP1 expression, a disorganized ZP assembles around growing oocytes
      and females exhibit reduced fertility. These observations are consistent with the
      current model for ZP structure in which ZP2 and ZP3 form long Z filaments
      crosslinked by ZP1.

PMID- 15237212
TI  - Notch-1, c-kit and GFRalpha-1 are developmentally regulated markers for
      premeiotic germ cells.
AB  - Culture, transfection and immortalization of mouse germ line stem cells, germ
      cell transplantation and grafting of testicular tissue are milestones of recent
      biotechnological breakthroughs. Alone and in combination they offer new pathways
      to explore the cellular mechanisms responsible for pluripotency and the
      requirements of cells to enter the germ line. Efficient markers, isolation and
      culture systems as well as transfection approaches are developed to elucidate the
      molecular and cellular mechanisms leading to the development of male germ line
      cells. Here, we describe the localization pattern of c-kit, Notch-1 and GFRalpha
      1 in postnatal, immature and adult testes. All three proteins are potentially
      useful markers for spermatogonial characterization and enrichment. First attempts
      and various future perspectives to use spermatogonial stem cells as pathway for
      the introduction of transgenes are discussed.

PMID- 15237213
TI  - Systems biology of the 2-cell mouse embryo.
AB  - The transcriptome of the 2-cell mouse embryo was analyzed to provide insight into
      the molecular networks at play during nuclear reprogramming and embryonic genome
      activation. Analysis of ESTs from a 2-cell cDNA library identified nearly 4,000
      genes, over half of which have not been previously studied. Transcripts of mobile
      elements, especially those of LTR retrotransposons, are abundantly represented in
      2-cell embryos, suggesting their possible role in introducing genomic variation,
      and epigenetic restructuring of the embryonic genome. Analysis of Gene Ontology
      of the 2-cell-stage expressed genes outlines the major biological processes that
      guide the oocyte-to-embryo transition. These results provide a foundation for
      understanding molecular control at the onset of mammalian development.

PMID- 15237214
TI  - Expression of the proliferation marker Ki-67 during early mouse development.
AB  - In somatic tissues, the mouse Ki-67 protein (pKi-67) is expressed in
      proliferating cells only. Depending on the stage of the cell cycle, pKi-67 is
      associated with different nuclear domains: with euchromatin as part of the
      perichromosomal layer, with centromeric heterochromatin, and with the nucleolus.
      In gametes, sex-specific expression is evident. Mature MII oocytes contain pKi
      67, whereas pKi-67 is not detectable in mature sperm. We investigated the re
      establishment of the cell cycle-dependent distribution of pKi-67 during early
      mouse development. After fertilization, male and female pronuclei exhibited very
      little or no pKi-67, while polar bodies were pKi-67 positive. Towards the end of
      the first cell cycle, prophase chromosomes of male and female pronuclei
      simultaneously got decorated with pKi-67. In 2-cell embryos, the distribution
      pattern changed, presumably depending on the progress of development of the
      embryo, from a distribution all over the nucleus to a preferential location in
      the nucleolus precursor bodies (NPBs). From the 4-cell stage onwards, pKi-67
      showed the regular nuclear relocations known from somatic tissues: during mitosis
      the protein was found covering the chromosome arms as a constituent of the
      perichromosomal layer, in early G1 it was distributed in the whole nucleus, and
      for the rest of the cell cycle it was associated with NPBs or with the nucleolus.

PMID- 15237215
TI  - Genetic and genomic approaches to study placental development.
AB  - Recent technological advances in genetic manipulation and expression profiling
      offer excellent opportunities to elucidate the molecular mechanisms controlling
      developmental processes during embryogenesis. Thus, this revolution also strongly
      benefits studies of the molecular genetics of placental development. Here we
      review the findings of several expression profiling analyses in extraembryonic
      tissues and assess how this work can contribute to the identification of
      essential components governing placental development. We further discuss the
      relevance of these components in the context of genetic manipulation experiments.
      In conclusion, the intelligent combination of genetic and genomic approaches will
      substantially accelerate the progress in identifying the key molecular pathways
      of placental development.

PMID- 15237216
TI  - Maternal and environmental factors in early cloned embryo development.
AB  - Cloning by somatic cell nuclear transfer (SCNT) in mammals has revealed the
      remarkable ability of an oocyte to reprogram somatic cell nuclei and induce them
      to recapitulate the developmental program. Despite the success, cloning remains
      very inefficient. This review summarizes recent observations from cloning in mice
      that reveal some of the likely causes for the present inefficiency. One cause
      appears to be the slow pace of reprogramming combined with the early onset of
      genome transcription, which together cause cloned embryos to elaborate many
      somatic cell characteristics even before the first cleavage division. The altered
      phenotypes of cloned embryos render standard embryo culture conditions grossly
      sub-optimum. Another cause appears to be a hitherto unappreciated contribution of
      spindle-associated factors to early embryo development. As current procedures
      remove the spindle and associated factors, cloned embryos lack these factors.
      These observations are providing new insight into basic mammalian embryology.
      They also reveal possible changes to protocols that could improve the overall
      success of cloning.

PMID- 15237218
TI  - Spatial genome organization during T-cell differentiation.
AB  - The spatial organization of genomes within the mammalian cell nucleus is non
      random. The functional relevance of spatial genome organization might be in
      influencing gene expression programs as cells undergo changes during development
      and differentiation. To gain insight into the plasticity of genomes in space and
      time and to correlate the activity of specific genes with their nuclear position,
      we systematically analyzed the spatial genome organization in differentiating
      mouse T-cells. We find significant global reorganization of centromeres,
      chromosomes and gene loci during the differentiation process. Centromeres were
      repositioned from a preferentially internal distribution in undifferentiated
      cells to a preferentially peripheral position in differentiated CD4+ and CD8+
      cells. Chromosome 6, containing the differentially expressed T-cell markers CD4
      and CD8, underwent differential changes in position depending on whether cells
      differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4
      and CD8 showed distinct behavior in their position relative to the chromosome 6
      centromere at various stages of differentiation. Our results demonstrate that
      significant spatial genome reorganization occurs during differentiation and
      indicate that the relationship between dynamic genome topology and single gene
      regulation is highly complex.

PMID- 15237217
TI  - Nuclear reprogramming in mammalian somatic cell nuclear cloning.
AB  - Nuclear cloning is still a developing technique used to create genetically
      identical animals by somatic cell nuclear transfer into unfertilized eggs.
      Despite an intensive effort in a number of laboratories, the success rate of
      obtaining viable offspring from this technique remains less than 5%. In the past
      few years many investigators reported the reprogramming of specific nuclear
      activities in cloned animals, such as genome-wide gene expression patterns, DNA
      methylation, genetic imprinting, histone modifications and telomere length
      regulation. The results highlight the tremendous difficulty the clones face to
      reprogram the original differentiation status of the donor nuclei. Nevertheless,
      nuclei prepared from terminally differentiated lymphocytes can overcome this
      barrier and produce apparently normal mice. Study of this striking nuclear
      reprogramming activity should significantly contribute to our understanding of
      cell differentiation in more physiological settings.

PMID- 15237219
TI  - DNA methylation in mouse gametogenesis.
AB  - DNA methylation is involved in many biological processes and is particularly
      important for both development and germ cell differentiation. Several waves of
      demethylation and de novo methylation occur during both male and female germ line
      development. This has been found at both the gene and all genome levels, but
      there is no demonstrated correlation between them. During the postnatal germ line
      development of spermatogenesis, we found very complex and drastic DNA methylation
      changes that we could correlate with chromatin structure changes. Thus, detailed
      studies focused on localization and expression pattern of the chromatin proteins
      involved in both DNA methylation, histone tails modification, condensin and
      cohesin complex formation, should help to gain insights into the mechanisms at
      the origin of the deep changes occurring during this particular period.

PMID- 15237220
TI  - DNA methylation profiles of CpG islands for cellular differentiation and
      development in mammals.
AB  - DNA methylation has been implicated in mammalian development. Transcription units
      contain CpG islands, but expression of CpG island associated genes in normal
      tissues was not believed to be controlled by DNA methylation. There are, however,
      numerous CpG islands containing tissue-dependent and differentially methylated
      regions (T-DMR), which are potential methylation sites in normal cells and
      tissues. Genomic scanning which focused on T-DMRs in CpG islands revealed that
      the DNA methylation profile of each cell/tissue is more complicated than
      previously considered. Differentiation of cells is associated with both
      methylation and demethylation, which occur at multiple loci. The epigenetic
      system characterized by DNA methylation requires cells to memorize gene
      expression patterns, thus, standardizing cellular phenotypes.

PMID- 15237221
TI  - Identification and properties of imprinted genes and their control elements.
AB  - Imprinted genes have the unusual characteristic that the copy from one parent is
      destined to remain inactive. Though few in number they nonetheless constitute a
      functionally important part of the mammalian genome. With their memory of
      parental origin, imprinted genes represent an important model for the epigenetic
      regulation of gene function and will provide invaluable paradigms to test whether
      we can predict epigenetic state from DNA sequence. Since their first discovery,
      systematic screens and some good fortune have led to identification of over
      seventy imprinted genes in the mouse and human: recent microarray analysis may
      reveal many more. With a significant number of imprinted genes now identified and
      completion of key mammalian genome sequences, we are able systematically to
      examine the organization of imprinted loci, properties of their control elements
      and begin to recognize common themes in imprinted gene regulation.

PMID- 15237222
TI  - Endogenous reverse transcriptase: a mediator of cell proliferation and
      differentiation.
AB  - Endogenous, non-telomeric Reverse Transcriptase (RT) is encoded by two classes of
      repeated genomic elements, retrotransposons and endogenous retroviruses, and is
      an essential component of the retrotransposition machinery of both types of
      elements. Expression of RT-coding genes is generally repressed in non
      pathological, terminally differentiated cells, but is active in early embryos,
      germ cells, embryo and tumor tissues, all of which have a high proliferative
      potential. To clarify whether reverse transcription is functionally implicated in
      control of cell growth, differentiation and in embryogenesis, recent experiments
      have been undertaken to inactivate the endogenous RT activity. RT was inhibited
      in normal and transformed cell lines by exposure to nevirapine, a non-nucleosidic
      RT inhibitor. The endogenous RT was also blocked in murine embryos by
      microinjection of an anti-RT antibody. Both experimental approaches yielded a
      dramatic inhibition of proliferation. Murine embryos arrested at pre-implantation
      stages. Transformed cell lines underwent a significant reduction in the rate of
      cell growth, concomitant with the induction of differentiation. In addition, RT
      inhibition induced an extensive reprogramming of the gene expression profile both
      in cultured cell lines and in preimplantation embryos. From these studies,
      endogenous RT begins to emerge as a key function with a driving role in normal
      and pathological developmental processes.

PMID- 15237223
TI  - Factors regulating endogenous retroviral sequences in human and mouse.
AB  - Endogenous retroviruses (ERVs) are stably integrated in the genome of vertebrates
      and inherited as Mendelian genes. The several human ERV (HERV) families and
      related elements represent up to 5-8% of the DNA of our species. ERVs may be
      involved in the regulation of adjacent genomic loci, especially promoting the
      tissue-specific expression of genes; some HERVs may have functional roles, e.g.,
      coding for the placental fusogenic protein, syncytin. This paper reviews the
      growing evidence about factors that may modulate ERVs, including: cell and tissue
      types (with special attention to placenta and germ cells), processes related to
      differentiation and aging, cytokines, agents that disrupt cell functions (e.g.,
      DNA hypomethylating agents) and steroids. Special attention is given to HERVs,
      due to their possible involvement in autoimmunity and reproduction, as well as
      altered expression in some cancer types; moreover, different HERV families may
      deserve specific attention, due to remarkable differences concerning, e.g.,
      expression in tissues. A comparison with factors interacting with murine ERV
      related sequences indicates that the mouse may be a useful model for studying
      some patterns of HERV regulation. Overall, the available evidence identifies the
      diverse, potential interactions with endogenous or exogenous factors as a
      promising field for investigating the roles of ERVs in physiology and disease.

PMID- 15237224
TI  - An integrative genomics approach to the reconstruction of gene networks in
      segregating populations.
AB  - The reconstruction of genetic networks in mammalian systems is one of the primary
      goals in biological research, especially as such reconstructions relate to
      elucidating not only common, polygenic human diseases, but living systems more
      generally. Here we propose a novel gene network reconstruction algorithm, derived
      from classic Bayesian network methods, that utilizes naturally occurring genetic
      variations as a source of perturbations to elucidate the network. This algorithm
      incorporates relative transcript abundance and genotypic data from segregating
      populations by employing a generalized scoring function of maximum likelihood
      commonly used in Bayesian network reconstruction problems. The utility of this
      novel algorithm is demonstrated via application to liver gene expression data
      from a segregating mouse population. We demonstrate that the network derived from
      these data using our novel network reconstruction algorithm is able to capture
      causal associations between genes that result in increased predictive power,
      compared to more classically reconstructed networks derived from the same data.

PMID- 15237225
TI  - Chromosomes and speciation in Mus musculus domesticus.
AB  - Thirty years after its identification, the model of chromosomal speciation in Mus
      musculus domesticus is reevaluated using the methods of population biology,
      molecular cytogenetics and functional genomics. Three main points are considered:
      (1) the structural predisposition of M. m. domesticus chromosomes to Robertsonian
      fusion; (2) the impediment of structural heterozygosity to gene flow between
      populations of mice with karyotypes rearranged by Robertsonian fusion and between
      them and populations with the standard all-acrocentric 40-chromosome karyotype;
      (3) the selective advantage of chromosomal novelty, essential for the attainment
      of homozygosis and the rapid fixation of the new karyotype in the population.

PMID- 15237226
TI  - Mouse biodiversity in the genomic era.
AB  - Comparative genomics has developed by comparison of distantly related genomes,
      for which the link between the reported evolutionary changes and species
      development/physiology/ecology is not obvious. It is argued that the mouse (genus
      Mus) is an optimal model for microevolutionary genomics in vertebrates. This is
      because the mouse genome sequence, physical and genetic map have been completed,
      because mouse genetics, morpho-anatomy, pathology, behavior and ecology are well
      studied, and because the Mus genus is a diverse, well- documented taxon, allowing
      comparative studies at the level of individual, population, subspecies, and
      species. The potential of the interaction between mouse genome and mouse
      biodiversity is illustrated by recent studies of speciation in the house mouse
      Mus musculus, and studies about the evolution of isochores, the peculiar pattern
      of GC-content variation across mammalian genomes.

PMID- 15237227
TI  - The tobacco mouse and its relatives: a "tail" of coat colors, chromosomes,
      hybridization and speciation.
AB  - The article reviews over 30 years' study of the chromosomal variation of the
      western house mice (Mus musculus domesticus) from the neighboring valleys of
      Poschiavo and Valtellina on the Swiss-Italian border. This is done in the context
      of the social and political history of this area, on the grounds that mice, as
      commensals, are influenced by human history. The chromosomal study of mice in
      this area was initiated because their unusual black coat color led a 19th century
      naturalist to describe the "tobacco mice" from Val Poschiavo as a separate
      species (Mus poschiavinus). The special coloration of the Val Poschiavo mice is
      matched by their chromosomes: they have 26 chromosomes instead of the usual 40.
      The Val Poschiavo mice are not a separate species according to the Biological
      Species Concept; instead they constitute a chromosome race (the "Poschiavo", POS)
      that is related to other races with reduced chromosome numbers that occur in N
      Italy (of which only those races in Val Poschiavo and Upper Valtellina have black
      coats). A phylogenetic analysis of mitochondrial DNA sequences suggests that the
      lineage of chromosome races found in N Italy was not formed during an extreme
      population bottleneck, although such bottlenecks have apparently occurred during
      the origin of individual races and certainly have influenced single populations.
      In one small, isolated population in Valtellina (Migiondo), two chromosome races
      (the POS and the "Upper Valtellina", UV, 2n = 24) became reproductively isolated
      from each other. In another small population (Sernio) bottlenecking led to
      fixation of a hybrid form with the UV karyotype and coat color, but with allozyme
      and microsatellite alleles characteristic of mice with the standard 40-chromosome
      karyotype. Two of the chromosome races in Valtellina (the UV and the "Mid
      Valtellina", MV, 2n = 24) also appear to be the product of hybridization. The
      dynamic history and patchy distribution of the house mouse chromosome races in
      Val Poschiavo and Valtellina in part reflects extinction-recolonization events;
      the formation of the UV and MV races and the introduction of the pale brown
      Standard race mice are believed to reflect such events. Dynamism in the
      chromosomal constitution of single populations is also evident from 25 years of
      data on the population in Migiondo. Due to change in agricultural practices,
      house mice in Valtellina and Val Poschiavo are becoming rarer, which is likely to
      have further impacts on the distribution and characteristics of the chromosome
      races in this area.

PMID- 15237228
TI  - Chromosome painting in the long-tailed field mouse provides insights into the
      ancestral murid karyotype.
AB  - We report on the hybridization of mouse chromosomal paints to Apodemus
      sylvaticus, the long-tailed field mouse. The mouse paints detected 38 conserved
      segments in the Apodemus karyotype. Together with the species reported here there
      are now six species of rodents mapped with Mus musculus painting probes. A
      parsimony analysis indicated that the syntenies of nine M. musculus chromosomes
      were most likely already formed in the muroid ancestor: 3, 4, 7, 9, 14, 18, 19, X
      and Y. The widespread occurrence of syntenic segment associations of mouse
      chromosomes 1/17, 2/13, 7/19, 10/17, 11/16, 12/17 and 13/15 suggests that these
      associations were ancestral syntenies for muroid rodents. The muroid ancestral
      karyotype probably had a diploid number of about 2n = 54. It would be desirable
      to have a richer phylogenetic array of species before any final conclusions are
      drawn about the Muridae ancestral karyotype. The ancestral karyotype presented
      here should be considered as a working hypothesis.

PMID- 15237229
TI  - RNAi knock-down mice: an emerging technology for post-genomic functional
      genetics.
AB  - RNA interference (RNAi) has been extensively used for sequence-specific silencing
      of gene function in mammalian cells. The latest major breakthrough in the
      application of RNAi technology came from experiments demonstrating RNAi-mediated
      gene repression in mice and rats. After more than two decades of functional mouse
      research aimed at developing and continuously improving transgenic and knock-out
      technology, the advent of RNAi knock-down mice represents a valuable new
      alternative for studying gene function in vivo. In this review we provide some
      basic insight as to how RNAi can induce gene silencing to then focus on recent
      findings concerning the applicability of RNAi for regulating gene function in the
      mouse. Reviewed topics will include delivery methods for RNAi-mediating
      molecules, a comparison between traditional knock-out and innovative transgenic
      RNAi technology and the generation of graded RNAi knock-down phenotypes. Apart
      from the exciting possibilities RNAi provides for studying gene function in mice,
      we discuss several caveats and limitations to be considered. Finally, we present
      prospective strategies as to how RNAi technology might be applied for generating
      conditional and tissue-restricted knock-down mice.

PMID- 15237230
TI  - Long dsRNA and silent genes strike back:RNAi in mouse oocytes and early embryos.
AB  - RNA interference (RNAi) refers to the selective degradation of mRNA induced by
      double-stranded RNA (dsRNA), first discovered in Caenorhabditis elegans. Homology
      dependent silencing phenomena related to RNAi have been observed in many species
      from all eukaryotic kingdoms. RNAi and related mechanisms share several conserved
      components. The hallmark of these phenomena is the presence of short dsRNA
      molecules (21-25 bp long), termed short interfering RNA (siRNA), which are
      generated from dsRNA by the activity of Dicer, a specific type III RNAse. These
      molecules serve as a template for the recognition and cleavage of the cognate
      mRNA. As it is beyond the scope of a single review to cover all aspects of RNAi,
      this review will focus on certain steps of the pathway relevant to mammals and on
      the use of long dsRNA to specifically silence genes in mammalian cells permissive
      to this technique, such as oocytes and early embryos.

PMID- 15237231
TI  - Sequence-specific modification of mouse genomic DNA mediated by gene targeting
      techniques.
AB  - The major impact of the human genome sequence is the understanding of disease
      etiology with deduced therapy. The completion of this project has shifted the
      interest from the sequencing and identification of genes to the exploration of
      gene function, signalling the beginning of the post-genomic era. Contrasting with
      the spectacular progress in the identification of many morbid genes, today
      therapeutic progress is still lagging behind. The goal of all gene therapy
      protocols is to repair the precise genetic defect without additional modification
      of the genome. The main strategy has traditionally been focused on the
      introduction of an expression system designed to express a specific protein,
      defective in the transfected cell. But the numerous deficiencies associated with
      gene augmentation have resulted in the development of alternative approaches to
      treat inherited and acquired genetic disorders. Among these one is represented by
      gene repair based on homologous recombination (HR). Simply stated, the process
      involves targeting the mutation in situ for gene correction and for restoration
      of a normal gene function. Homologous recombination is an efficient means for
      genomic manipulation of prokaryotes, yeast and some lower eukaryotes. By
      contrast, in higher eukaryotes it is less efficient than in the prokaryotic
      system, with non-homologous recombination being 10-50 fold higher. However,
      recent advances in gene targeting and novel strategies have led to the suggestion
      that gene correction based on HR might be used as clinical therapy for genetic
      disease. This site-specific gene repair approach could represent an alternative
      gene therapy strategy in respect to those involving the use of retroviral or
      lentiviral vectors to introduce therapeutic genes and linked regulatory sequences
      into random sites within the target cell genome. In fact, gene therapy approaches
      involving addition of a gene by viral or nonviral vectors often give a short
      duration of gene expression and are difficult to target to specific populations
      of cells. The purpose of this paper is to review oligonucleotide-based gene
      targeting technologies and their applications on modifying the mouse genome.

PMID- 15237232
TI  - Sox genes and cancer.
AB  - Sox genes encode transcription factors belonging to the HMG (High Mobility Group)
      superfamily. They are conserved across species and involved in a number of
      developmental processes. In vitro studies have shown at least one Sox gene to be
      capable of inducing oncogenic transformation of fibroblast cells. In addition,
      overexpression and/or amplification of Sox genes are associated with a large
      number of tumour types in vivo. We review here the available evidence linking Sox
      gene expression and cancer, and show that this link is supported by extensive EST
      database analysis. This work provides a basis for further studies aimed at
      investigating the possible role of Sox genes in the oncogenic process.

PMID- 15237233
TI  - Genetic modifiers in mice: the example of the fragile X mouse model.
AB  - Modifiers play an important role in most, if not all human diseases, and mouse
      models. For some disease models, such as the cystic fibrosis knockout mouse
      model, the effect of genetic factors other than the causative mutation has been
      well established and a modifier gene has been mapped. For other mouse models,
      including those of the fragile X syndrome, a common form of inherited mental
      retardation, controversies between test results obtained in different
      laboratories have been well recognized. Yet, the possibility that modifiers could
      at least explain part of the discrepancies is only scarcely mentioned. In this
      review we compare the test results obtained in different laboratories and provide
      evidence that modifiers may affect disease severity in the fragile X knockout
      mouse.

PMID- 15237234
TI  - The role of replicative senescence in cancer and human ageing: utility (or
      otherwise) of murine models.
AB  - Replicative senescence has the potential both to act as an anti-tumour mechanism,
      and to contribute to age-related changes in tissue function. Studies on human
      cells have revealed much, both about the nature of cell division counters, some
      of which utilize the gradual erosion of chromosomal telomeres, and the downstream
      signalling pathways that initiate and maintain growth arrest in senescence. A
      powerful test of the hypothesis that senescence is linked to either ageing or
      tumour prevention now requires a suitable animal model system. Here we overview
      the current understanding of replicative senescence in human cells, and address
      to what extent the senescence of murine cells in culture mirrors this phenomenon.
      We also discuss whether examples of telomere-independent senescence, such as
      those seen in mouse embryonic fibroblasts (MEFs) and several human cells types,
      should be viewed not as a consequence of "inadequate growth conditions", but
      rather as a powerful potential model system to dissect the selective pressures
      that occur in the early stages of tumour development, ones that we speculate lead
      to the observed high frequency of abrogation of p16INK4a function in human
      cancer.

PMID- 15237235
TI  - Telomere length measurement in mouse chromosomes by a modified Q-FISH method.
AB  - Telomeres are physical ends of mammalian chromosomes that dynamically change
      during the lifetime of a cell or organism. In order to understand mechanisms
      responsible for telomere dynamics, it is necessary to develop methods for
      accurate telomere length measurement. The most sensitive method for measuring
      telomere length in mouse chromosomes is quantitative fluorescence in situ
      hybridization (Q-FISH). The usual protocol for Q-FISH requires plasmids with
      variable numbers of telomeric repeats and fluorescence beads as calibration
      standards. Here, we describe a Q-FISH protocol in which two mouse lymphoma cell
      lines with well-defined telomere lengths are used as calibration standards. Using
      this protocol we demonstrate that reproducible results can be obtained in a set
      of four different mouse cell lines. This method can be adapted so that any pair
      of mammalian cell lines can serve as an internal calibration standard.

PMID- 15237236
TI  - Manipulating mouse telomeres: models of tumorigenesis and aging.
AB  - Telomeres are capping structures at the ends of chromosomes, composed of a
      repetitive DNA sequence and associated proteins. Both a minimal length of
      telomeric repeats and telomere-associated binding proteins are necessary for
      proper telomere function. Functional telomeres are essential for maintaining the
      integrity and stability of eukaryotic genomes. The capping structure enables
      cells to distinguish chromosome ends from double strand breaks (DSBs) in the
      genome. Uncapped chromosome ends are at great risk for degradation,
      recombination, or chromosome fusion by cellular DNA repair systems. Dysfunctional
      telomeres have been proposed to contribute to tumorigenesis and some aging
      phenotypes. The analysis of mice deficient in telomerase activity and other
      telomere-associated proteins has allowed the roles of dysfunctional telomeres in
      tumorigenesis and aging to be directly tested. Here we will focus on the analysis
      of different mouse models disrupted for proteins that are important for telomere
      functions and discuss known and proposed consequences of telomere dysfunction in
      tumorigenesis and aging.

PMID- 15237237
TI  - Genetics of rare diseases of the kidney: learning from mouse models.

PMID- 15237238
TI  - Nitric oxide levels in preterm and term infants and in premature infants with
      bacteremia.
AB  - OBJECTIVE: To determine the serum nitric oxide levels in healthy neonates and in
      infants with bacteremia. METHODS: We performed a prospective study in a tertiary
      neonatal intensive care unit. The serum nitric oxide levels were measured in all
      infants at birth (basal) and in the infected neonates also on the first 2 days of
      bacteremia. RESULTS: Thirty-three neonates (10 term, 23 preterm) were included.
      Eleven preterm infants (mean gestational age 27 weeks) had bacteremia. The main
      blood culture isolates included coagulase-negative staphylococci (n=4),
      Klebsiella pneumoniae (n=3), and Escherichia coli (n=3). The serum nitric oxide
      levels increased during infection in 10 infants (p <0.008). The mean nitric oxide
      level before infection was 44 microM and during infection 96 microM (p=0.008). In
      the healthy babies, the mean nitric oxide level was 26 microM in those with a
      gestational age <27 weeks, 44 microM in those born between 28 and 36 weeks of
      gestation, and 63 microM in term infants. CONCLUSIONS: Bacteremic preterm infants
      produce significantly higher amounts of nitric oxide. The basal nitric oxide
      levels at birth may be correlated with gestational age.

PMID- 15237239
TI  - CoQ10 plasmatic levels in breast-fed infants compared to formula-fed infants.
AB  - BACKGROUND: Coenzyme Q10 has been recognized as an important antioxidant factor
      besides its main role in bioenergetic metabolism. CoQ10 tissue levels depend both
      on exogenous dietetic intake and on endogenous biosynthesis, as this compound can
      be partly synthesized in human cells. Q10 plasma levels reflect the tissue
      content of the coenzyme and can be used to evaluate the presence of this compound
      in the human organism. DESIGN/METHODS: Aim of the study was to measure CoQ10
      plasmatic levels in a newborn breast-fed population and to compare them to CoQ10
      levels in a newborn formula-fed population in order to verify whether changes in
      CoQ10 plasmatic contents could be related to a different dietetic intakes. We
      measured CoQ10 plasmatic levels in 25 healthy term neonates with different
      dietetic intakes: 15 breast-fed and 10 bottle-fed with a common infant formula.
      These infants were evaluated prospectively during the first month of life. The
      analyses were performed on the mothers' blood samples and cord blood samples at
      the time of delivery, then on infants at 4 and 28 days of age. RESULTS: Our
      results showed markedly reduced Q10 levels in cord blood samples compared to
      maternal Q10 plasmatic levels at the time of delivery, suggesting placental
      impermeability towards this molecule or increased fetal utilization during labor
      and delivery. At 4 days of age Q10 levels had increased in both groups of
      neonates, but significantly more in breast-fed infants compared to formula-fed
      babies (p <0.05). At 4 weeks of age no significant changes occurred in breast-fed
      infants, while values increased significantly in formula-fed infants (p <0.05).
      The content of Q10 in breast milk samples was lower than in infant formula.
      CONCLUSIONS: The results of this study show that CoQ10 plasmatic levels are at
      least partly influenced by the exogenous dietetic supply.

PMID- 15237240
TI  - Use of once-daily netilmicin to treat infants with suspected sepsis in a neonatal
      intensive care unit.
AB  - Once-daily administration of aminoglycoside antibiotics has become the most
      acceptable dosing schedule for the majority of patients. There are few published
      data on the impact of post-natal age on aminoglycoside concentrations in preterm
      infants receiving once-daily dosage regimens. Netilmicin was administered as a
      once-daily dose of 4 mg/kg. In 141 episodes of suspected sepsis in 123 babies,
      trough netilmicin concentrations ranged from undetectable to 4.0 mg/l. Netilmicin
      concentrations were above a level of 2 mg/l in 10.6% of episodes. Netilmicin
      concentrations decreased with increasing post-natal age and weight. Levels were
      higher in males compared to females. Increased creatinine concentrations were
      associated with higher netilmicin concentrations. This study emphasises the
      importance of post-natal age as a determinant of aminoglycoside concentrations
      with a once-daily dosing regimen in a neonatal intensive care population. Trough
      levels should be carefully monitored and consideration given to extending dosage
      intervals particularly when netilmicin is administered once daily to preterm
      infants in the first week of life.

PMID- 15237241
TI  - The Tei index permits evaluation of cardiopulmonary function during inhaled
      nitric oxide therapy in the hypoxic newborn piglet.
AB  - The purpose of this study was to test the effectiveness of a new Doppler index
      combining systolic and diastolic time intervals (the Tei index) in the
      prospective assessment of ventricular function and pulmonary circulation in a
      newborn piglet model with hypoxic pulmonary hypertension during inhaled nitric
      oxide (NO). Piglets were prepared for the experiments under normal air, hypoxia,
      and hypoxia-with-inhaled-NO conditions. Complete two-dimensional Doppler
      echocardiographic examinations were performed in each condition. The right
      ventricle (RV) Tei index increased with hypoxia and decreased following the
      inhalation of NO. Furthermore, there was a direct correlation between the
      individual changes in the RV Tei index and individual changes in mean pulmonary
      arterial pressure in each condition. We conclude that the Tei index is useful for
      assessing cardiac function and pulmonary circulation in hypoxic pulmonary
      hypertension during inhaled NO. These results suggest that the Tei index provides
      an objective assessment of persistent pulmonary hypertension of the newborn.

PMID- 15237242
TI  - Sketches of otohistory. Part 3: Alfonso Corti.

PMID- 15237243
TI  - Late calcineurin inhibitor withdrawal as a strategy to prevent graft loss in
      patients with suboptimal kidney transplant function.
AB  - Chronic allograft nephropathy is a major cause of progressive renal failure in
      renal transplant recipients. Its etiology is multifactorial and may include both
      immunologic and nonimmunologic causes. In this observational cohort study we set
      out to see if calcineurin inhibitor withdrawal would reduce the likelihood of
      graft loss. METHODS: One hundred and five renal transplant recipients with
      impaired kidney function (mean serum creatinine 3.0 +/- 0.1 mg/dl) and biopsy
      proven chronic allograft nephropathy had the dose of their calcineurin
      inhibitors, cyclosporine (CSA), or tacrolimus (FK), reduced or discontinued with
      either the addition of, or continuation of mycophenolate mofetil and low-dose
      corticosteroids. This intervention occurred at a mean of 29.0 +/- 2.7 months
      after transplantation. Follow-up after intervention was 54.3 +/- 4.1 months in
      the reduced CSA group (n = 64), 41.6 +/- 3.2 months in the reduced FK group (n =
      28), and 75.5 +/- 6.7 months in the calcineurin inhibitor withdrawal group (n =
      13). RESULTS: There were 24 graft failures in the reduced CSA group, 9 graft
      failures in the reduced FK group, and 1 graft lost in the calcineurin inhibitor
      withdrawal group. The unadjusted relative risk for graft failure in the CSA and
      FK groups combined (confidence interval 1.05-31.6), was 4.07 using the
      calcineurin inhibitor withdrawal group as the reference, p = 0.05. A Cox
      proportional hazards model adjusting for baseline covariates including age,
      gender, race, type of transplant, delayed graft function, baseline blood pressure
      and random serum glucose and cholesterol demonstrated that only calcineurin
      inhibitor dose reduction but not withdrawal, older age, delayed graft function,
      higher serum creatinine at the time of intervention, and higher diastolic blood
      pressure and serum glucose, correlated with graft loss. Only 6 of the 105
      patients developed Banff grade acute rejection. All responded to steroid therapy.
      We conclude that although this observational cohort study may have a selection
      bias, late calcineurin inhibitor withdrawal in patients with chronic allograft
      nephropathy and impaired kidney function appears safe and durable as a treatment
      strategy to reduce the likelihood of graft failure.

PMID- 15237244
TI  - Relevance of anger and irritability in outpatients with major depressive
      disorder.
AB  - INTRODUCTION: Current psychiatric classification systems underestimate the part
      played by anger and aggressiveness in unipolar depression. This study was
      designed to assess the relevance of anger, irritability, aggressiveness,
      hostility, and psychomotor activation in major depressive disorder. METHODS: A
      total of 222 newly admitted consecutive outpatients with major depressive
      disorder (mean age 48.9 years, 64.4% females) were enrolled in the study. They
      had no comorbid axis I or II DSM-IV disorder, and they received no treatment with
      antidepressants in the preceding 2 months. They were assessed with the SVARAD, a
      validated scale for the rapid assessment of the main psychopathological
      dimensions. Principal component analysis was performed on SVARAD items. RESULTS:
      We obtained a three-factor solution accounting for 47.4% of total variance. The
      factors were interpreted as 'anger/irritability', 'depression', and 'anxiety',
      respectively. The anger/irritability dimension was clinically relevant in 23% of
      patients. Anger/aggressiveness was especially frequent (21.6%), whereas
      psychomotor activation was infrequent (0.9%). DISCUSSION: In depressive
      disorders, there are psychopathological dimensions other than depressed mood and
      anxiety that deserve greater clinical recognition and research. Our study
      suggests that one of these symptom clusters includes anger, irritability,
      aggressiveness, and hostility. The relevance of this dimension was not related to
      concurrent pharmacological treatment. Misdiagnosis of bipolar II disorder is also
      unlikely to explain our findings. Possibly, personality factors might at least
      partly explain the occurrence of anger and aggressiveness in several depressed
      patients. Attachment theory suggests that anger might also be conceived as part
      of the protest-despair-detachment reaction to a loss, either actual or symbolic.

PMID- 15237245
TI  - Nonschizophrenic psychotic disorders: the case of cycloid psychoses.
AB  - BACKGROUND: Cycloid psychosis is a psychiatric disorder known for about 100
      years. This disorder is at present partly and simplified represented in the ICD
      10. SAMPLING AND METHODS: Over a period of 15 months, 139 consecutively acutely
      admitted psychotic patients were assessed, by means of different diagnostic
      instruments, in order to investigate the prevalence and the symptom profile of
      cycloid psychoses. In addition, the concordance between the diagnoses cycloid
      psychosis, brief psychotic disorder, and acute polymorphic psychotic disorder
      with or without symptoms of schizophrenia was calculated. RESULTS: Cycloid
      psychoses were present in 13% of the patients. There was a significant but small
      overlap with the DSM brief psychotic disorder and the ICD acute polymorphic
      psychotic disorder. CONCLUSIONS: This study demonstrates that cycloid psychoses
      can be identified with the proper diagnostic instruments in a proportion that is
      also found in other studies. Since this type of psychosis entails a distinct
      prognosis and may require a specific treatment, its identification is of clinical
      importance. Limitations are the nature of the psychiatric facility with an
      inherent bias in the selection of patients and the lack of a long-term
      evaluation.

PMID- 15237246
TI  - Clinical, psychopathological and personality correlates of interoceptive
      awareness in anorexia nervosa, bulimia nervosa and obesity.
AB  - OBJECTIVE: To determine the levels of interoceptive awareness (IA), which
      measures the ability of an individual to discriminate between sensations and
      feelings, and between the sensations of hunger and satiety, in eating disorder
      patients and to identify the clinical, psychopathological and personal variables
      correlated with IA. SAMPLING AND METHODS: Sixty-one restrictor anorectics, 61
      binge-purging anorectics, 104 purging bulimics, 49 obese subjects with binge
      eating disorder (BED) and 47 obese subjects without BED were compared. They were
      assessed with the Eating Disorder Inventory-2, the Temperament and Character
      Inventory, and the Beck Depression Inventory, and their clinical and
      sociodemographic features were recorded. RESULTS: In all patients, the levels of
      IA were higher than the 'normal' ones; in bulimia nervosa, they were higher than
      in anorexia nervosa and obesity. Similar personal features and eating attitudes
      are shared by patients with bulimia nervosa and BED. In the total sample, the
      following variables independently correlate with IA: the Beck Depression
      Inventory, self- directedness and persistence. CONCLUSIONS: The importance of an
      altered IA in eating disorders is supported. Both depression and a perfectionist
      and poorly self-directive personality can lead to greater difficulties in
      discriminating hunger and satiety.

PMID- 15237247
TI  - Correlates of coping styles in psychotic illness.
AB  - BACKGROUND: Both integration and sealing over have been identified as global,
      clinically distinct coping styles with the psychotic illness and integration was
      found to be associated with a better outcome. We studied a series of potential
      correlates of these coping styles. SAMPLING AND METHODS: A total of 75
      psychiatric patients in a recovery phase after a psychotic episode were studied.
      All patients filled out the Frankfurt Self-Concept Inventory and the Parental
      Bonding Instrument; the Integration/Sealing over Scale and the Positive and
      Negative Syndrome Scale were completed by an investigator for all patients during
      a semistructured interview. Besides, some sociodemographic and clinical data were
      collected. RESULTS: A relationship was found between the integrative coping style
      and absence of negative symptoms, housing with partner or alone indicating more
      social competence and a diagnosis of psychotic illness other than (paranoid)
      schizophrenia. CONCLUSIONS: As only 25% of the variance were explained, other-
      still unknown--factors are also of importance.

PMID- 15237248
TI  - Prevalence of congenital hypothyroidism in Isfahan, Iran: results of a survey on
      20,000 neonates.
AB  - AIMS: To evaluate the prevalence of congenital hypothyroidism (CH) in a screening
      program performed for the first time in Isfahan, Iran. METHODS: From May 2002 to
      December 2002, T4 and TSH serum concentrations of 20,000 3- to 7-day-old
      newborns, born in all 17 hospitals of the city, were measured by radioimmunoassay
      and immunoradiometric assay, respectively. The newborns with abnormal screening
      results (TSH >20 mIU/l, T4 <6.5 microg/dl and based on the weight) were re
      examined. RESULTS: Of 531 recalled subjects (recall rate 2.6%), 54 were confirmed
      to be hypothyroid, showing a prevalence of 1:370 for CH. CONCLUSION: Considering
      the high frequency of CH, the necessity of implementing a routine screening
      program in the healthcare system of Isfahan Province is emphasized.

PMID- 15237249
TI  - Urinary incontinence: its prevalence, risk factors and effects on the quality of
      life of women living in a region of Turkey.
AB  - BACKGROUND: The aim of this population-based cross-sectional study was to
      determine the prevalence and risk factors of urinary incontinence (UI) in women
      aged 20 years or older and to assess its influence on the quality of life (QOL).
      MATERIALS AND METHODS: The study group was comprised of 625 women determined
      using the stratified sampling technique according to age and residence. The data
      were collected through a questionnaire and the Urinary Incontinence Quality of
      Life Instrument. RESULTS: The prevalence of UI was 25.8%. UI was significantly
      associated with body mass index (OR 12.75, 95% CI 6.68-24.6), diabetes mellitus
      (OR 3.55, 95% CI 1.44-8.73), neurological disorders (OR 3.80, 95% CI 1.69-8.58),
      recurrent urinary tract infections (OR 4.73, 95% CI 2.52-8.88). Impairment of QOL
      was related with the type of UI, frequency of UI episodes, amount of leakage and
      UI during sexual intercourse. CONCLUSION: Our study results determined that UI is
      common in women. The QOL of women was either mildly and moderately affected by
      UI.

PMID- 15237250
TI  - Current clinical spectrum of neurosyphilis in immunocompetent patients.
AB  - BACKGROUND: Neurosyphilis (NS) is nowadays a less frequent disease. Its incidence
      and clinical spectrum have changed over time. OBJECTIVE: To estimate the
      incidence of NS and describe the clinical spectrum of NS in immunocompetent
      patients in the last decade. METHODS: Demographic and clinical features,
      cerebrospinal fluid (CSF) changes, neuroimaging findings and outcome were
      retrospectively analyzed. RESULTS: Forty-three patients met NS criteria. The
      yearly incidence was 0.2- 2.1 cases per 100,000 inhabitants. The mean age was
      48.1 years, males being more frequently involved. The most frequent clinical
      patterns were meningovascular (30.2%), meningeal (25.6%) and general paresis
      (25.6%). Compared to prepenicillin series, we observed a decrease in late forms,
      mainly tabes dorsalis. CSF titers studied by the Venereal Disease Research
      Laboratory were higher in early NS. Neuroimaging findings were nonspecific.
      Outcome was better for early forms. CONCLUSIONS: Compared to the preantibiotic
      era, a lower frequency of late NS was observed, similar to that reported in other
      modern series which include patients with HIV infection. Therefore, this trend
      seems to be due to the impact of antibiotics rather than to HIV infection.

PMID- 15237251
TI  - Focal monophasic demyelinating leukoencephalopathy in advanced HIV infection.
AB  - A multiple sclerosis (MS)-like illness has been reported in human
      immunodeficiency virus (HIV)-infected patients, usually in the early stages of
      HIV infection. We report 3 patients with advanced HIV infection (CD4 lymphocyte
      count under 200/mm(3)) presenting with monophasic focal leukoencephalopathy, in
      whom biopsy demonstrated demyelinating lesions compatible with acute MS lesions.
      In 1 patient, recently started on highly active antiretroviral therapy, MS-like
      disease could represent an immune reconstitution syndrome. The lesions were
      reversible in 2 patients, but rapidly fatal in the third patient. These cases
      show that an MS-like disease may present in advanced HIV infection as focal
      monophasic leukoencephalopathy with either a reversible or fulminating course,
      mimicking progressive multifocal leukoencephalopathy.

PMID- 15237252
TI  - Longitudinal cerebral perfusion decrease in mild alzheimer's disease revealed by
      SPECT with statistical parametric mapping method.
AB  - Fifteen patients with mild Alzheimer's disease received baseline and follow-up
      technetium-99m hexamethylpropylene amine oxime SPECT examinations paired with
      neuropsychological assessments, including the Cognitive Ability Screening
      Instruments (CASI). The differences between baseline and follow-up SPECT images
      were analyzed by the voxel-based paired t test of the statistical parametric
      mapping technique. A simple regression analysis was also conducted to analyze the
      correlation between CASI sub-scores and both sets of SPECT images. In comparison
      with baseline images, cerebral perfusion at follow-up was significantly reduced
      in the left superior and middle temporal gyri, right middle and inferior temporal
      gyri, and right fusiform gyrus. A significant correlation was demonstrated
      between the list-generating fluency CASI sub-score and perfusion of the left
      fusiform gyrus. The visual construction sub-score was significantly correlated
      with perfusion of the right superior and medial frontal gyri.

PMID- 15237253
TI  - Development of an early diagnostic system using fuzzy theory for postoperative
      infections in patients with gastric cancer.
AB  - BACKGROUND: Early prediction of infection following surgery for gastric cancer
      may permit earlier intervention. AIM: The aim was to develop an early diagnostic
      system for postoperative infection. METHODS: Clinical and laboratory data were
      analyzed in 180 patients who had surgery for gastric cancer at the Wakayama
      Medical University Hospital (January 1992 to December 1994). Of these, 60
      patients developed a postoperative infection. A predictive system was then
      devised using fuzzy theory and evaluated in a second set of 137 patients who
      underwent surgery for gastric cancer at Wakayama Medical University and 10 other
      associated hospitals (August 1995 to January 1997). RESULTS: The system
      identified seven parameters grouped into six rules and entered into a fuzzy logic
      system to predict either infection or non-infection. (1) Blood loss, and extent
      of resection; (2) the febrile pattern during days 2 to 4; (3) differential
      leukocyte count on day 4; (4) C-reactive protein level on day 4; (5) time
      sequential vectors during days 1-4 for the band cell neutrophil count, and (6)
      leukocyte count. The sensitivity was 86% (24/28), the specificity was 90%
      (98/109), the negative predictive value was 96% (98/102), the positive predictive
      value was 69% (24/35) and the overall accuracy was 80% (122/137). CONCLUSION:
      Fuzzy theory can provide early prediction of postoperative infection using
      standard clinical and biochemical parameters. The clinical utility of this system
      needs to be determined in future studies.

PMID- 15237254
TI  - Hand-assisted laparoscopic splenectomy for splenic tumors.
AB  - BACKGROUND: The feasibility of hand-assisted laparoscopic splenectomy (HALS) for
      splenic tumors including benign or malignant neoplasms and the associated
      clinical outcome of the patients remain unclear. METHODS: A total of 10 patients
      with splenic tumors undergoing HALS were retrospectively analyzed in this study.
      The intraoperative course, postoperative course, and postoperative recovery were
      evaluated. RESULTS: Ten patients with splenic tumors consisted of 5 with benign
      tumors and 5 with malignant tumors. HALS was not converted to an open splenectomy
      in any of the patients. Mean operative time was 170 min (range 100-310 min). Mean
      estimated blood loss was 105 g (range 10-900 g). Mean splenic size and splenic
      weight was 13 cm and 478 g, respectively. Splenomegaly based on size or weight
      occurred in 50% of the patients. There were no intra- or postoperative
      complications. Postoperative chemotherapy was given to 4 patients with malignant
      tumors including metastatic carcinomas and malignant lymphomas. All the patients
      were alive at a mean follow-up of 26 months, ranging from 15 to 43 months after
      surgery. There was no port-site recurrence after surgery in our study. Mean time
      to first flatus, mean time to first walking, mean time to resumption of oral
      intake, mean length of hospital stay, and mean duration of epidural analgesia
      were 1.8, 1, 1.5, 10.8 and 3.1 days, respectively. The results were equal in
      terms of intra- and postoperative course to those seen with a standard
      laparoscopic splenectomy for 13 patients with idiopathic thrombocytopenic
      purpura. CONCLUSION: HALS may be a good indication for malignant tumors as well
      as benign tumors of the spleen.

PMID- 15237255
TI  - Leakage testing at the time of surgical oesophageal myotomy.
AB  - BACKGROUND: Surgical myotomy is a well-established and validated method to treat
      severe gastro-oesophageal motor disorders such as achalasia. The benign character
      of these diseases further substantiates the importance of operating with greatest
      possible safety margins. We presently report our experiences with the use of
      perioperative leakage testing. MATERIALS AND METHODS: Thirty-seven consecutive
      patients are reported of whom 30 had a laparoscopic, 3 a thoracoscopic and 4 an
      open operation. The indications for an operation were in 3 patients oesophageal
      spasm, in 30 patients newly diagnosed achalasia and 4 patients had an open
      reoperation due to a previous incomplete myotomy plus epiphrenic diverticulum.
      Thirty patients had a perioperative endoscopy with gas insufflation and a leakage
      test, whereas the others did not. RESULTS: A previously unrecognised oesophageal
      mucosal tear was discovered during the test and repaired in 4 of the 30 tested
      cases whereafter everyone had an uneventful postoperative recovery. Among the
      remaining 7 untested patients, 3 developed clinical signs of leakage of whom 1
      had an immediate reoperation. The postoperative courses were in all those
      prolonged and complicated. CONCLUSION: Perioperative use of endoscopy at the time
      of completion of the surgical myotomy is a useful tool to document leakage.
      Thereby the safety profile of the operation can be further enhanced.

PMID- 15237256
TI  - Treatment of hydatid disease of the liver. Evaluation of a UK experience.
AB  - BACKGROUND: Hydatid disease of the liver though endemic in many countries, is
      rare in the UK. We evaluated a 16-year experience of treating hydatidosis using a
      management protocol combining surgery with anti-scolicidals. PATIENTS AND
      METHODS: There were 30 patients. 14 (47%) males, median age 41 (range 25-72)
      years, of whom 21 (70%) were symptomatic. Diagnosis was by serological tests and
      imaging. All had disease confined to the liver and received peri-operative anti
      scolicidal drug therapy. RESULTS: The initial 4 (13%) patients received
      praziquantel combined with albendazole for 2 weeks and the following 26 (87%)
      patients received two cycles of albendazole 400 mg twice daily for 28 days, with
      a 14-day break in between. However, 2 (7%) patients could not tolerate
      albendazole, one due to GI side effects and the other developed deranged liver
      functions. These 2 patients subsequently received praziquantel for 2 weeks. All
      patients underwent surgery. Subtotal cystectomy was carried out on 29 (96%)
      patients and 1 patient required a segmentectomy. Cystobiliary communications were
      identified in 15 (50%) of patients which were oversewn using fine absorbable
      sutures. Of these, 7 had the bile ducts decompressed using a T tube, with only 1
      developing a post-operative bile leak. In comparison, 8 were not drained of which
      6 leaked (p = 0.03). The median post-operative hospital stay was 8 days (range 5
      24). Patients who developed post-operative bile leaks, however, needed prolonged
      abdominal drainage for a median of 21 days (range 18-24). Two (7%) patients
      developed histologically proven recurrent disease. The median follow-up was 56
      months (range 3-87). CONCLUSION: Surgery combined with anti-scolicidal therapy
      proved effective. Cystobiliary communications are common and, when identified,
      should result in the biliary system being drained, to avoid post-operative bile
      leaks.

PMID- 15237257
TI  - Diagnostic evaluation of patients with faecal incontinence at a specialist
      institution.
AB  - BACKGROUND: Evaluation of the anorectal function, clinically, structurally, and
      functionally, in patients with faecal incontinence should ensure appropriate and
      individual treatment. METHODS: Two hundred and twenty-six patients with faecal
      incontinence were reviewed regarding disease history and results of anorectal
      physiological tests and anal ultrasonography. RESULTS: The mean age was 54 years,
      and 191 patients (85%) were female. Sixty-two patients had passive faecal
      incontinence only, 49 had urge faecal incontinence only, and 115 had both passive
      and urge faecal incontinence. Patients with passive faecal incontinence only had
      a significantly higher voluntary contraction pressure and less external sphincter
      abnormalities than patients with urge faecal incontinence or both passive and
      urge faecal incontinence. The structural abnormalities of the internal and
      external anal sphincters identified on anal ultrasonography were significantly
      associated with a low maximum resting pressure and with a low voluntary
      contraction pressure, respectively. The causes identified for this faecal
      incontinence were: in 90 patients idiopathic, in 76 obstetric injury, in 36
      internal anal sphincter degeneration, in 20 anal surgical injury, in 6 rectal
      prolapse, and in 9 patients miscellaneous. CONCLUSIONS: The anal sphincter
      structure as demonstrated by ultrasonography was closely related to the anorectal
      function, as determined by anorectal physiological tests, and the observations
      from these were reflected in the range of patient-reported symptoms. Anal
      ultrasonography and anorectal physiological tests are useful tools, enabling us
      to identify the mechanisms and causes of faecal incontinence in at least 60% of
      the patients.

PMID- 15237258
TI  - Outcome of duodenum-preserving resection of the head of the pancreas for
      intraductal papillary-mucinous neoplasm.
AB  - BACKGROUND: The standard surgical procedure for intraductal papillary-mucinous
      neoplasm of the pancreatic head is pylorus-preserving pancreatoduodenectomy. A
      less extensive resection may be justified because most intraductal papillary
      mucinous neoplasms are benign or of low-grade malignancy. AIMS AND METHODS: The
      outcome of duodenum-preserving pancreatic head resection with preservation of the
      main bile duct was evaluated retrospectively in 13 patients with a branch-type
      intraductal papillary-mucinous neoplasm in the head of the pancreas and with a
      median (range) follow-up of 60.0 (0.3-99.5) months. RESULTS: Post-operative
      complications included anastomotic leakage (n=3), bile duct perforation (n=1),
      intra-abdominal bleeding (n=3), delayed gastric emptying (n=2) and death (n=2).
      All the resection margins were clear of tumour on histological examination. Ten
      of 11 patients maintained over 90% of their pre-operative body weight. Glucose
      tolerance improved in 4 of 11 evaluable patients, was unchanged in 6 and worsened
      in 1 patient. Biliary scintigraphy showed that bile flow was delayed compared
      with that before surgery (8.8 +/- 1.1 vs. 19.6 +/- 4.6 min; p = 0.03). Neither
      recurrence nor metastasis was observed. CONCLUSION: The results of duodenum
      preserving pancreatic head resection for branch duct-type intraductal papillary
      mucinous neoplasm were satisfactory and provided a good quality of life.

PMID- 15237259
TI  - Esophageal perforation associated with cervical spine surgery: report of two
      cases and review of the literature.
AB  - BACKGROUND/AIMS: Esophageal perforation after anterior cervical spine surgery is
      a rare complication with various clinical presentations and treatments. METHODS:
      Two cases of esophageal perforation after anterior cervical spine surgery are
      described, one occurring in the immediate postoperative period and one several
      years after plate stabilization of the cervical spine. RESULTS: Primary suturing
      of the acute perforation and diversion of the salivary flow by means of T-tube
      placement after delayed presentation allowed successful healing of the esophageal
      defects. CONCLUSION: When encountering acute dysphagia after cervical spine
      surgery, one should think of an esophageal perforation and install immediate
      further diagnostics and therapy. Treatment depends on the time of detection and
      size of the perforation. In early stages, with vital tissues, primary suturing is
      the treatment of choice. If presentation is late, it seems advisable to limit the
      procedure to simple drainage after removal of foreign bodies.

PMID- 15237260
TI  - Ofuji papulo-erythroderma: a reappraisal of the deck-chair sign.

PMID- 15237261
TI  - Is sentinel lymph node biopsy of therapeutic relevance for melanoma?
AB  - INTRODUCTION: It is still unclear whether sentinel lymph node biopsy (SLNB) has
      an effect on the survival or recurrence-free survival of patients. It would be
      necessary to compare patients with SLNB (or with selective lymph node dissection
      in the case of positive SLNB) and patients without SLNB who received only a close
      clinical and sonographic follow-up. To date, no results from prospective,
      randomized studies of SLNB are available. MATERIAL AND METHODS: Patients with
      SLNB (n = 283) and patients in clinical stage I and II with close follow-up
      examinations only (n = 3,514) were studied retrospectively in this investigation
      with regard to prognostic factors established in the literature: sex, age, tumor
      thickness, histological tumor type, ulceration and localization. RESULTS:
      Multivariate analysis did not show an independent significant advantage with
      regard to survival when SLNB had been performed (p = 0.37). Compared with
      patients in clinical stage I and II with close follow-up only (n =
      2,617),patients in stage I and II with negative SLNB (n = 238) had no
      significantly lower melanoma-related mortality (p =0.36) but significantly fewer
      recurrences in the regional lymph node area (p = 0.0015). With regard to survival
      without distant metastases and disease-specific survival, patients with positive
      SLNB (n = 33) did not significantly benefit by comparison with patients who
      developed lymph node metastasis identified clinically or sonographically later
      during follow-up examinations (n = 246; p =0.89 and p = 0.38, respectively).
      CONCLUSION: In the relatively short follow-up period after SLNB, patients for
      whom SLNB had been performed did not have - on the whole - a prognostic advantage
      over patients who were subject only to close follow-up monitoring. Patients for
      whom subclinical lymph node metastases had been removed as the result of a
      positive SLNB did not have a better prognosis than patients without SLNB who had
      developed lymph node metastases within the follow-up period [corrected]

PMID- 15237262
TI  - German adaptation of the Skindex-29 questionnaire on quality of life in
      dermatology: validation and clinical results.
AB  - BACKGROUND: Health-related quality of life (HRQOL) has increasingly been
      recognized as an important aspect of a comprehensive clinical assessment in
      dermatology. OBJECTIVE: The aim of the present study was to translate and
      validate one of the most frequently used and established skin disease-specific
      HRQOL questionnaires originally developed in English for the German language
      area: the Skindex-29. METHODS: 295 in-patients with psoriasis and atopic
      dermatitis completed the German translation of the Skindex as well as a number of
      additional skin disease-specific questionnaires. Data from 2 subsamples were
      analysed separately to test for the robustness of results. RESULTS: Results from
      principal component analyses supported the scale structure of the original
      Skindex. Internal consistency coefficients were high for all scales. Further
      analyses supported the convergent validity of the German adaptation of the
      Skindex-29 as well as its sensitivity to change. CONCLUSION: The study provides
      evidence for the validity and reliability of the Skindex-29.

PMID- 15237263
TI  - In situ Expression of CD40 and CD40 ligand in psoriasis.
AB  - BACKGROUND: The interaction between CD40 and CD40 ligand (CD40L) provides a
      signal that contributes to the initiation of cellular immune responses. However,
      little information on the in vivo expression of CD40 and CD40L in cutaneous
      inflammation has been reported. OBJECTIVE: To investigate the potential role of
      CD40-mediated signals in the pathogenesis of psoriasis. MATERIALS AND METHODS: In
      situ CD40 and CD40L expression was examined immunohistochemically in different
      stages of psoriatic lesions: fully developed and initial pinpoint. RESULTS: In
      normal skin, faintly positive immunoreactivity for CD40 was seen in the basal
      keratinocytes and dermal endothelial cells. These showed almost the same
      intensity as that seen in psoriatic lesional skin. In the dermal infiltrates of
      psoriatic lesions, CD40 was intensely expressed and some of these positive cells
      appeared to be dendritic in shape. Whereas CD40 expression was observed almost in
      all specimens of psoriatic lesions, the expression of CD40L was predominantly
      detected in the initial pinpoint lesions of psoriasis. These seemed to be
      distributed close to CD40-positive cells. CONCLUSION: These results suggested
      that CD40L-triggered signals could be involved in the early stage of psoriatic
      lesion formation.

PMID- 15237264
TI  - Successful desensitization to fixed drug eruption: the presence of CD25+CD4+ T
      cells in the epidermis of fixed drug eruption lesions may be involved in the
      induction of desensitization.
AB  - BACKGROUND: Fixed drug eruption (FDE) is a distinct type of drug-induced
      eruption, in which intraepidermal CD8+ T cells in the lesional skin are the final
      effector cells in the epidermal injury of FDE. Desensitization is a unique
      approach for the management of drug eruption, which has been reported to be
      effective in treating FDE. However, the mechanisms underlying desensitization to
      FDE are quite unknown. OBJECTIVE AND METHODS: We reported a case of successful
      desensitization to allopurinol-induced FDE. To clarify the mechanisms underlying
      desensitization to FDE, we examined the phenotype of T cells in the epidermis of
      FDE lesions before and after desensitization using flow cytometry. RESULTS: The
      overwhelming majority of intraepidermal T cells in the FDE lesion before
      desensitization consisted of CD8+ T cells, whereas a significant number of
      CD25+CD4+ T cells were present in the epidermis of FDE lesions after
      desensitization. CONCLUSION: The presence of CD25+CD4+ T cells in the epidermis
      of FDE lesions may be involved in the induction of desensitization to FDE.

PMID- 15237265
TI  - Family history and risk of hair loss.
AB  - INTRODUCTION: The genetic basis of androgenetic alopecia (AGA) is well accepted
      in the medical community and among the general population. However, rigorous
      studies investigating the familial basis of AGA are lacking. The purpose of the
      current study was to explore the relationship between family history and
      expression of AGA in a sample of men from the general community. METHODS: Hair
      loss was assessed by an independent observer trained by an expert dermatologist
      using the Norwood/Hamilton classification scale and a 7-point global description
      of hair loss. Men were classified into two groups, one as having little or no
      hair loss and the other having hair loss. The family history of hair loss in
      parents and grandparents was assessed by subject self-report. RESULTS: Adjusting
      for age, men whose fathers had hair loss were 2.5 times as likely to have had
      some level of hair loss compared to men whose fathers had no hair loss (95% CI:
      1.3-4.9). Likewise, men whose fathers had hair loss were twice as likely to have
      hair loss than men whose fathers had no hair loss even after adjusting for age
      (OR = 2.1, 95% CI: 1.2-3.7 and OR = 2.5, 95% CI: 1.4-4.7 for Norwood/Hamilton and
      global description of hair loss assessments, respectively). CONCLUSION: Results
      suggest that the probability of male pattern hair loss is dependent on family
      history and age. Hair loss in a man's father also appears to play an important
      role in increasing a man's risk of hair loss, either in conjunction with a
      history of hair loss in the mother or hair loss in the maternal grandfather.

PMID- 15237266
TI  - Human papillomavirus and extragenital in situ carcinoma.
AB  - BACKGROUND: The relation between human papillomavirus (HPV) and extragenital
      Bowen's disease (BD) is controversial. METHODS: This study used in situ
      hybridisation to evaluate the rate of HPV in extragenital cutaneous BD and
      investigated possible relations with immune status and exposure of skin to light.
      RESULTS: HPV DNA was detected in 58% of 69 samples from 50 patients. The
      percentage of HPV detection was not significantly higher in exposed (55%) than
      unexposed areas (65%), and no difference in HPV rate was found between
      immunosuppressed and immunocompetent patients. CONCLUSION: Thus, this study
      confirms the high rate of HPV detection in extragenital cutaneous BD and suggests
      that there is no apparent relation concerning exposed areas and immune status.

PMID- 15237268
TI  - Nephrogenic fibrosing dermopathy in a renal transplant recipient with
      tubulointerstitial nephritis and uveitis.
AB  - We report a patient with nephrogenic fibrosing dermopathy. He had chronic renal
      failure with arthritis, uveitis and histologically severe tubulointerstitial
      nephritis for which he received a renal transplant from a family relative. After
      an episode of acute renal failure with the transplant he developed painful,
      erythematous, firm papules and plaques with geographic borders on the legs,
      anterior thorax and elbow. A skin biopsy revealed increased fibroblast and
      collagen fiber content of the dermis and subcutaneous septae. Mucin deposition,
      sparse smooth-muscle-actin-positive cells and an increased number of CD34
      positive cells in the deep dermis were found. After several weeks of
      hemodialysis, the lesions changed from an inflammatory to a purely sclerotic
      phase. The fibrocyte, a recently described circulating cell type, that is
      deposited in scar tissue may be involved in the pathogenesis of this novel
      pseudosclerodermatous skin disorder.

PMID- 15237267
TI  - Comparison of intralesionally injected zinc sulfate with meglumine antimoniate in
      the treatment of acute cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis is an endemic disease in developing
      countries. The first-line drugs for its treatment are the pentavalent antimony
      compounds such as meglumine antimoniate (MA). High cost, side effects, multiple
      injections and incomplete efficacy are limitations of this therapy. Zinc sulfate
      (ZS) has been reported to be effective in the treatment of cutaneous
      leishmaniasis. OBJECTIVE: To compare the efficacy of intralesional injections of
      ZS 2% with those of MA in the treatment of cutaneous leishmaniasis. METHODS: This
      was a prospective, double-blind, case-control clinical study. 104 patients with
      typical lesions of acute cutaneous leishmaniasis (ACL) were included. The
      duration of treatment was 6 weeks. Improvement was evaluated by clinical
      examination and direct smear. RESULTS: The study was completed in only 66
      patients: 35 patients received MA and 31 received ZS. The cure rates were 60% for
      MA and 83.8% for ZS. After the second and fourth weeks, the efficacy of treatment
      with ZS was higher than that with MA (p < 0.01), but after 6 weeks no significant
      differences were observed between the two groups (p > 0.05). CONCLUSION: On the
      basis of this trial and despite the high number of drop-outs, we consider that
      the intralesional injection of ZS 2% is an alternative treatment in ACL.

PMID- 15237269
TI  - Acute generalized exanthematic pustulosis: a case and an overview of side effects
      affecting the skin caused by celecoxib and other COX-2 inhibitors reported so
      far.
AB  - A 55-year-old woman who was treated for periarthritis humeroscapularis with
      celecoxib (Celebrex) developed a generalized pustular exanthema on the head and
      upper trunk, accompanied by fever, leukocytosis and increased erythrocyte
      sedimentation rate. The histological findings were subcorneal pustules, necrotic
      keratinocytes, edema in the upper dermis and polymorphic perivascular
      infiltrates. Four days after stopping celecoxib, the pustules disappeared without
      any treatment. Four weeks after disappearance of the skin lesions, celecoxib
      demonstrated a positive lymphocyte stimulation test. In this article, we present
      to our knowledge the first case of acute generalized exanthematic pustulosis
      caused by celecoxib, and we give an overview of the side effects affecting the
      skin caused by celecoxib and other cyclooxygenase type 2 inhibitors reported so
      far.

PMID- 15237272
TI  - Hypocalcemia: a sign of severity of necrotizing fasciitis.

PMID- 15237270
TI  - Langerhans cell histiocytosis and juvenile xanthogranuloma. Two case reports.
AB  - BACKGROUND: Histiocytoses represent a large, puzzling group of diseases which may
      involve the skin and other organs. At present, juvenile xanthogranuloma is the
      disorder most often confused with Langerhans cell histiocytosis. A complex
      overlap exists between juvenile xanthogranuloma and Langerhans cell
      histiocytosis, with lesions showing clinical and/or pathological features of both
      disorders. OBSERVATIONS: We report 2 patients affected by Langerhans cell
      histiocytosis who, during chemotherapy, presented cutaneous lesions with clinical
      and histological features of juvenile xanthogranuloma. During the therapy, in
      both cases, histological examination of new biopsies revealed the presence of
      Touton giant cells in the dermis with a few histiocytic cells;
      immunohistochemical staining was negative for CD1a, and no Birbeck granules were
      seen by ultrastructural examination. RESULTS AND CONCLUSION: A possible
      explanation for the link between Langerhans cell histiocytosis and juvenile
      xanthogranuloma regards the lineage development and the relationships of
      histiocytes. We suggest that chemotherapy can modify the production of cytokines
      by influencing the conversion or 'maturation' of pathological cells into
      macrophages or xanthomatous cells and fusing them to form multinucleated giant
      Touton cells. In our opinion, the modification of the cutaneous lesions during
      chemotherapy in Langerhans cell histiocytosis patients, as observed in our cases,
      could be a favorable prognostic factor.

PMID- 15237271
TI  - Panniculitis induced by specific venom immunotherapy.

PMID- 15237273
TI  - Isomorphic response in eruptive xanthomas.

PMID- 15237274
TI  - Mycophenolate mofetil in extensive Alopecia areata: no effect in seven patients.

PMID- 15237276
TI  - Combination of bexarotene and psoralen-UVA therapy in a patient with Mycosis
      fungoides.

PMID- 15237277
TI  - Erythema elevatum et diutinum, multiple sclerosis and interferon beta.

PMID- 15237275
TI  - Prevention and treatment of keloids with intralesional verapamil.

PMID- 15237281
TI  - Initial therapy of hypertension.

PMID- 15237280
TI  - Ginkgo biloba compared with cholinesterase inhibitors in the treatment of
      dementia: a review based on meta-analyses by the cochrane collaboration.
AB  - Data were derived from the Cochrane Collaboration meta-analyses of the efficacies
      of ginkgo, donepezil, rivastigmine and galantamine on changes in cognitive
      function in patients with dementia and, where necessary, were transformed to
      standardized mean differences. The proportion of patients discontinuing trials
      was used as a proxy measure of tolerability. Outcomes were assessed after 6
      months of treatment. Trial data for cholinesterase inhibitors were more
      consistent than those for ginkgo, particularly regarding patient populations and
      outcome measures. Significant benefits on cognition vs. placebo were seen with
      donepezil, 5 and 10 mg, rivastigmine, 6-12 mg, and galantamine, 16 and 24 mg.
      Significant benefit vs. placebo with ginkgo was seen only when all doses were
      pooled. Similar proportions of patients discontinued treatment with ginkgo and
      placebo. Cholinesterase inhibitors were also well tolerated, although a
      significantly greater proportion of patients receiving active treatment
      discontinued vs. placebo with some doses. An evidence-based medicine approach,
      taking into account the quality of clinical trials, is essential when assessing
      the safety and efficacy of medications.

PMID- 15237278
TI  - Temporomandibular arthritis in a patient with psoriasis vulgaris under systemic
      etretinate therapy.

PMID- 15237282
TI  - Amlodipine/atorvastatin (Caduet).

PMID- 15237283
TI  - Intramedullary spinal cord metastasis of ovarian tumor.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report a case of a thoracic
      intramedullary spinal cord metastasis of ovarian tumor in a 59-year-old woman.
      SETTING: Shiga, Japan. CASE REPORT: A case of a thoracic intramedullary spinal
      cord metastasis of ovarian tumor in a 59-year-old woman is reported. She received
      abdominal ovariectomy for the ovarian adenocarcinoma 4 years before she suffered
      from back pain and showed neurological symptoms. The thoracic intramedullary
      lesion was confirmed by preoperative magnetic resonance imaging. She showed
      complete paralysis before operation. The excision of the tumor was achieved
      through the posterior approach. Histologically, the diagnosis of metastasis of
      adenocarcinoma was made. CONCLUSION: Although she did not show any postoperative
      neurologic recovery, her general condition was good and there was no evidence of
      recurrence 24 months after surgery.

PMID- 15237284
TI  - Does early decompression improve neurological outcome of spinal cord injured
      patients? Appraisal of the literature using a meta-analytical approach.
AB  - STUDY DESIGN: Definitive and unequivocal evidence to support the practice of
      early or late surgery is still lacking in clinical studies. Accordingly, meta
      analysis is one of the few methods that offer a rational, statistical approach to
      management decision. A review of the clinical literature on spinal cord injury
      with emphasis on the role of early surgical decompression and a meta-analysis of
      results was performed. OBJECTIVES: To determine whether neurological outcome is
      improved in traumatic spinal cord-injured patients who had surgery within 24 h as
      compared with those who had late surgery or conservative treatment. METHODS: A
      Medline search covering the period 1966-2000, supplemented with manual search,
      was used to locate studies containing information on indication, rationale and
      timing of surgical decompression after spinal cord injuries. The analysis
      included a total of 1687 eligible patients. RESULTS: Statistically, early
      decompression resulted in better outcome compared with both conservative
      (P<0.001) and late management (P<0.001). Nevertheless, analysis of homogeneity
      showed that only data regarding patients with incomplete neurological deficits
      who had early surgery were reliable. CONCLUSIONS: Although statistically the
      percentage of patients with incomplete neurological deficits improving after
      early decompression appear 89.7% (95% confidence interval: 83.9, 95.5%), to be
      better than with the other modes of treatment when taking into consideration the
      material available for analysis and the various other factors including clinical
      limitations; early surgical decompression can only be considered as practice
      option for all groups of patients.

PMID- 15237285
TI  - Abductor hallucis for monitoring lower-limb recovery after spinal cord injury in
      man.
AB  - STUDY DESIGN: Electromyogram (EMG) study on patients with acute spinal cord
      injury (SCI). OBJECTIVES: We hypothesized that subjects with mild to moderate
      acute SCI would have a higher probability of recovering function in intrinsic
      muscles of the foot compared to more proximal lower-limb muscles, based on the
      relative density of corticospinal tract innervation to these different motoneuron
      pools. SETTING: Miami and Syracuse, USA. METHODS: We conducted repeated measures
      of EMG during voluntary contractions from lower-limb muscles in subjects with
      acute traumatic SCI. For this study, analysis was restricted to those subjects
      who had either no recruitment (ie 'motor-complete') or limited recruitment (ie
      'motor-incomplete') in any lower-limb muscle of either leg during the initial
      evaluation, and all of whom had converted to a motor-incomplete status in one or
      both legs at the time of final evaluation. Recruitment of the abductor hallucis
      (AbH) muscle during contraction attempts was judged as being either 'present' or
      'absent', based upon the presence or absence of EMG-based volitional motor unit
      recruitment. RESULTS: A total of 70 subjects were included in this study. Of
      these, 58 had motor-incomplete injury at or rostral to the T10 vertebral level,
      and another 12 had injury caudal to T10. In the former group, the AbH muscle
      showed a recovery probability that was considerably higher than that of other
      lower-limb muscles. Quite the opposite pattern was seen in persons with injury
      caudal to T10. In these subjects, recruitment was more common in proximal muscles
      of the thigh (psoas and quadriceps), and least common in the AbH muscle.
      DISCUSSION: For persons with SCI at or rostral to the T10 vertebral level, the
      AbH muscle proved to be an earlier and more sensitive indicator of lower-limb
      contraction recovery following acute SCI compared to other lower-limb muscles.
      Including this intrinsic muscle of the foot as part of a neurologic assessment of
      muscle function after SCI should increase the test's sensitivity to preserved (or
      restored) supraspinal motor influence over lower-limb motoneuron pools, and is
      recommended.

PMID- 15237287
TI  - Arsenic's not so bad! Research profile of Kevin A. Francesconi.

PMID- 15237288
TI  - Sediment quality in the Douro river estuary based on trace metal contents,
      macrobenthic community and elutriate sediment toxicity test (ESTT).
AB  - The aim of this study was to evaluate the sediment quality in the mesotidal Douro
      River estuarine environment, in order to identify areas where sediment
      contamination could cause ecosystem degradation. Samples were obtained in five
      locations and sediment characterised for grain size, total organic matter, total
      recoverable metals (Al, Fe, Cu, Pb, Cr, Ni, Cd, Zn and Mn), as well as acid
      volatile sulfide (AVS) and simultaneously extracted metals (SEM). In situ effects
      were evaluated by examining the macrobenthic community structure. An elutriate
      sediment toxicity test (ESTT) was used to estimate the amount of metals and
      nutrients that could be exchanged with the water column through resuspension, and
      its positive or negative effects on the growth of the micro-alga Emiliania
      huxleyi in a 10 day test. Anthropogenic metal contamination was identified at the
      north bank of the Douro estuary, with deleterious effects on the macrobenthic
      community, namely decrease in number of species and diversity. This contamination
      could possibly also be toxic for water column organisms, in case of resuspension,
      as shown by the ESTT. Sediments from the salt marsh at the south bank showed an
      impoverished macrobenthic community and elutriate toxicity, which appeared to be
      due to anaerobic conditions. This study clearly shows the usefulness of the ESST
      approach to assess the biological effect of resuspension of estuarine sediments.

PMID- 15237289
TI  - Bio-analytical and chemical characterisation of offshore produced water effluents
      for estrogen receptor (ER) agonists.
AB  - The in vitro estrogen receptor (ER) agonist potency and C1 to C9 alkyl
      substituted phenol content of offshore produced water effluents collected from
      the UK sector of the North Sea were determined using a combination of bio
      analytical and chemical analysis techniques. An in vitro reporter gene assay was
      used to determine ER agonist potency, whilst gas chromatography coupled to mass
      spectrometry (GC-MS) was used to quantify the concentration of alkylphenols. The
      in vitro ER agonist potency was highly variable and ranged from less than the
      limit of detection (theoretically 0.03 ng 17beta-estradiol (E2) l(-1)) to 91 ng
      E2 l(-1). C1 to C5 alkylphenol concentrations were also highly variable ranging
      from 5 to 1600 microg l(-1) with a median concentration of 206 microg l(-1).
      These data reflect the highly variable composition of produced water discharges
      from different fields. The observed poor correlation of the alkylphenol isomer
      content and ER agonist activity suggests that other compounds present in the
      produced water discharges may be responsible for the ER agonist activity
      observed. It is recommended that further work be performed to characterise the
      full range of ER agonists present in offshore produced water discharges.

PMID- 15237290
TI  - Organophosphate flame retardants and plasticisers in wastewater treatment plants.
AB  - Previous studies have revealed that chlorinated and non-chlorinated
      organophosphorous flame retardants and plasticisers are important contaminants in
      German surface waters and it has been demonstrated that wastewater treatment
      plants contribute to the emission of these substances. In this study temporal
      development as well as elimination efficiency were determined in two wastewater
      treatment plants (STP) in the Ruhr/Rhine area at different stages of the
      wastewater treatment process. The samples were analysed for the non-chlorinated
      organophosphate esters tri-n-butylphosphate (TnBP), tri-iso-butylphosphate
      (TiBP), tris-(butoxyethyl)-phosphate (TBEP) and triphenylphosphate (TPP) and the
      chlorinated organophosphate esters tris-(2-chloro, 1-methylethyl)-phosphate
      (TCPP), tris-(2-chloro-, 1-chloromethylethyl)-phosphate (TDCP) and tris-(2
      chloroethyl)-phosphate (TCEP). The study showed that there were significant
      differences in the elimination of chlorinated and non-chlorinated
      organophosphorous flame retardants. The elimination rates ranged from 57-86% for
      TiBP, TnBP and TBEP at both STP's. No elimination of the chlorinated flame
      retardants TCPP, TDCP and TCEP was observed in any of the sampled STPs. At both
      STPs the first treatment steps and the final filtration did not contribute to the
      elimination of the non-chlorinated organophosphorous flame retardants while the
      aeration step did. At both STPs the efficiency of the cleaning process concerning
      the flame retardants was comparable. Thus the type of construction of the STP was
      not relevant for the elimination of these substances. Additionally a strong day
      to-day variation was observed, while in one STP a temporal trend for TCPP during
      the week was found.

PMID- 15237291
TI  - Determination of technical grade isocyanates used in the production of
      polyurethane plastics.
AB  - A method for determination of technical grade isocyanates used in the production
      of polyurethane (PUR) is presented. The isocyanates in technical grade products
      were characterised as di-n-butylamine (DBA) derivatives using LC-MS and LC
      chemiluminescent nitrogen detection (CLND) and the total isocyanate content was
      compared to a titration assay. For collection of isocyanates in air, an impinger
      filter sampling technique with DBA as derivatisation reagent was used.
      Characterised DBA and nonadeuterium labelled DBA derivatives of isocyanates in
      technical products were used as calibration standards and internal standards,
      respectively, in the analysis of air samples. Three workplaces were studied where
      PUR products were produced either by spraying or by moulding. In both technical
      products and in air samples, a number of monomeric, oligomeric and prepolymeric
      isocyanates of e.g. methylenebisphenyl diisocyanate (MDI) and hexamethylene
      diisocyanate (HDI) were characterised. Several of these have not previously been
      described in workplace atmospheres. In the technical isocyanate products, between
      69 and 102% of the NCO content determined by titration was accounted for by LC
      CLND. Quantifications of a wide range of isocyanates in air samples were
      performed with correlation coefficients in the range 0.988-0.999 (n= 8) and the
      instrumental detection limits were 0.7-25 pg. At the two workplaces where MDI-
      and HDI isocyanurate-based products were sprayed, the isocyanate composition in
      the air reflected the composition in the technical product. At the workplace
      where a MDI-based product was used in a moulding process, only the monomeric
      isocyanates were found in the air. The advantage of using characterised technical
      grade isocyanates as analytical standards was clearly demonstrated and the
      possibility of using index compounds when monitoring isocyanate exposure is
      discussed.

PMID- 15237292
TI  - Quantitative PCR analysis of house dust can reveal abnormal mold conditions.
AB  - Indoor mold concentrations were measured in the dust of moldy homes (MH) and
      reference homes (RH) by quantitative PCR (QPCR) assays for 82 species or related
      groups of species (assay groups). About 70% of the species and groups were never
      or only rarely detected. The ratios (MH geometric mean : RH geometric mean) for 6
      commonly detected species (Aspergillus ochraceus, A. penicillioides, A. unguis,
      A. versicolor, Eurotium group, and Cladosporium sphaerospermum) were >1 (Group
      I). Logistic regression analysis of the sum of the logs of the concentrations of
      Group I species resulted in a 95% probability for separating MH from RH. These
      results suggest that it may be possible to evaluate whether a home has an
      abnormal mold condition by quantifying a limited number of mold species in a dust
      sample. Also, four common species of Aspergillus were quantified by standard
      culturing procedures and their concentrations compared to QPCR results. Culturing
      underestimated the concentrations of these four species by 2 to 3 orders of
      magnitude compared to QPCR.

PMID- 15237294
TI  - Determination of airborne anhydrides using LC-MS monitoring negative ions of di-n
      butylamine derivatives.
AB  - An air sampling method for simultaneous determination of organic acid anhydrides
      and isocyanates is presented. Air samples are collected in impinger flasks filled
      with 0.01 M di-n-butylamine (DBA) in a mixture of toluene-acetonitrile (7:3, v/v)
      with a 13 millimetre glass fibre filter in series. The amount of anhydrides and
      isocyanates are determined as their amide and urea derivatives using LC-MS. Four
      anhydrides, maleic anhydride (MA), phthalic anhydride (PA), tetrahydrophthalic
      anhydride (TA) and cis-hexahydrophthalic anhydride (HA) and 11 isocyanates could
      be separated in 9 minutes using gradient elution. Anhydride-DBA derivatives in
      standard solutions were quantified using LC with chemiluminescent nitrogen
      detection (CLND). Anhydride-DBA derivatives were found to be stable for at least
      two months when stored in acetonitrile or toluene in the freezer. The yield of
      DBA derivatives of anhydrides in the 0.01 M DBA in toluene-acetonitrile (7:3,
      v/v) was in the range of 70->95%. Using MS and negative electrospray ionisation
      (ES-) linear calibrations curves were obtained for the anhydrides with
      correlation coefficients ranging from 0.9970-0.9997. The instrumental detection
      limit for the anhydrides ranged from 10-30 fmol, based on a signal to noise root
      mean square (RMS) ratio of 3. Monitoring positive and negative ions
      simultaneously, both isocyanates and anhydrides could be determined as their DBA
      derivatives in the same chromatographic run. When air samples were collected
      during thermal degradation of different coated metal sheets both anhydrides and
      isocyanates were present in the same samples and all the studied anhydrides were
      found.

PMID- 15237293
TI  - Determination of CH4, CO2 and N2O in air samples and soil atmosphere by gas
      chromatography mass spectrometry, GC-MS.
AB  - A method for determination of the climate gases CH4, CO2 and N2O in air samples
      and soil atmosphere was developed using GC-MS. The method uses straightforward
      gas chromatography (separation of the gases) with a mass spectrometric detector
      in single ion mode (specific determination). The gases were determined with high
      sensitivity and high sample throughput (18 samples h(-1)). The LOD (3sigma) for
      the gases were 0.10 micro L L(-1) for CH4, 20 microL L(-1) for CO2 and 0.02
      microL L(-1) for N2O. The linear range (R2 = 0.999) was up to 500 microL L(-1)
      for CH4, 4000 microL L(-1) for CO2 and 80 microL L(-1) for N2O. The samples were
      collected in 10 mL vials and a 5 microL aliquot was injected on column. The
      method was tested against certified gas references, the analytical data gave an
      accuracy within +/-5% and a precision of +/-3%. The presence of < or = 10% by
      volume of C2H2 (often used experimentally to prevent N2 formation from N2O) did
      not interfere with detection for the targeted trace gases.

PMID- 15237295
TI  - Evaluation of a novel passive sampling technique for monitoring volcanogenic
      hydrogen sulfide.
AB  - A novel, low-cost passive sampling procedure for monitoring of volcanogenic
      hydrogen sulfide is reported. The technique is based on absorption of H2S onto
      treated sections of photographic paper, which are housed in plastic film
      canisters during exposure. The H2S reacts with silver halide in the photographic
      paper, causing a colour-change reaction from white, through brown, to black,
      depending on concentration of atmospheric H2S. The sampler is sensitive to << 30
      ppb to approximately 1000 ppb of H2S. Here we present results from a series of
      optimization and quantification experiments. An active sampling procedure for
      rapid H2S measurement is also reported, based on absorption of H2S onto Whatman
      No. 41 cellulose filters treated with silver nitrate, and was shown to be
      quantitative using a single filter at flow rates <1.0 L min(-1) for collection of
      <200 microg of sulfide (as H2S). Determination of sulfide collected on the
      substrates was performed using a rapid flow-injection technique based on the
      fluorescence quenching of fluorescein mercuric acetate (FMA) by sulfide. This was
      optimized at a FMA concentration of 8 mg L(-1), at which 100% quenching was
      obtained at a solution sulfide concentration of 3 mg L(-1).

PMID- 15237296
TI  - Plants as indicators of urban air pollution (ozone and trace elements) in Pisa,
      Italy.
AB  - A biennial integrated survey, based on the use of vascular plants for the
      bioindication of the effects of tropospheric ozone, was performed in the area of
      Pisa (Tuscany, Central Italy). It also investigated the distribution of selected
      trace elements in plants and the data were compared with those obtained from the
      use of passive samplers, automatic analysers of ozone and lichen biodiversity.
      Photochemically produced ozone proved to be present during the warm season, with
      maximum hourly means surpassing 100 ppb: the use of supersensitive tobacco Bel-W3
      confirmed the value of detailed, cost-effective, monitoring surveys. Trials with
      clover clones demonstrate that sensitive plants undergo severe biomass reduction
      in the current ozone regime. The mean NC-S (clover clone sensitive to ozone):NC-R
      (resistant) biomass ratio ranged from 0.7 (in 1999) to 0.5 (in 2000). The
      economic impact of these reductions deserves attention. The data obtained using
      passive ozone samplers exceeded those obtained using an automatic analyser. The
      mapping of epiphytic lichen biodiversity was not related to the geographical
      ozone distribution as can be seen from the tobacco's response. Lettuce plants
      grown under standardized conditions were used positively as bioaccumulators of
      trace elements: Pb was abundantly recovered, but a large portion of this element
      was removed by washing.

PMID- 15237297
TI  - Requirements for developing a regional monitoring capacity for aerosols in Europe
      within EMEP.
AB  - The European Monitoring and Evaluation Programme (EMEP) has been established to
      provide information to Parties to the Convention on Long Range Transboundary Air
      Pollution on deposition and concentration of air pollutants, as well as on the
      quantity and significance of long-range transmission of pollutants and
      transboundary fluxes. To achieve its objectives with the required scientific
      credibility and technical underpinning, a close integration of the programme's
      main elements is performed. These elements are emission inventories, chemical
      transport modelling, and the monitoring of atmospheric chemistry and deposition
      fluxes, which further are integrated towards abatement policy development. A
      critical element is the air pollution monitoring that is performed across Europe
      with a focus not only on health effect aspects and compliance monitoring, but
      also on process studies and source receptor relationships. Without a strong
      observational basis a predictive modelling capacity cannot be developed and
      validated. Thus the modelling success strongly depends on the quality and
      quantity of available observations. Particulate matter (PM) is a relatively
      recent addition to the EMEP monitoring programme, and the network for PM mass
      observations is still evolving. This article presents the current status of EMEP
      aerosol observations, followed by a critical evaluation in view of EMEP's main
      objectives and its model development requirements. Specific recommendations are
      given for improving the PM monitoring programme within EMEP.

PMID- 15237298
TI  - Effects of different speeds of induction with sevoflurane on the EEG in man.
AB  - The effects of two kinds of induction speed of sevoflurane anesthesia on the EEG
      pattern were compared in the same individual using medical student volunteers: a
      first exposure of 4% was given, followed after full recovery, by incremental
      doses of 1, 2 and 4% successively, each being administered for 10 min. The
      arterial blood level of the anesthetic was measured using gaschromatograph. The
      changes of EEG pattern during fast induction with 4% were not represented by the
      abbreviation of those observed during the slow induction with the incremental
      doses. The administration of 4% induced a sudden appearance of high voltage,
      rhythmic slow waves of 2-3 Hz at 1-3 min when the arterial blood anesthetic level
      increased maximally, which was then followed by a pattern of faster activities of
      10-14 Hz mixed with 5-8 Hz slow waves. In contrast, the administration of
      incremental doses induced an increase in frequency and amplitude of EEG
      activities in the light plane, followed by their decreases in deeper planes. The
      final EEG patterns were identical for both these methods of induction. These
      findings confirmed our previous hypothesis that not only the arterial blood level
      of anesthetics but the rate of its increase are important factors determining the
      EEG pattern of anesthesia

PMID- 15237299
TI  - The effect of Fluosol-DA on the reticuloendothelial system in surgical patients.
AB  - The effect of Fluosol-DA (Perfluorochemicals), an oxygen carrying blood
      substitute, on the function of the reticuloendothelial system (RES) was
      investigated by means of Ferrichondroitin sulfate in a series of patients
      undergoing gastrectomy for cancer of the stomach. In 20 patients, 500 ml of blood
      were replaced with the same amount of either Fluosol-DA or hydroxyethylstarch
      (HES) prior to surgery. Changes of perioperative cellular immunity were studied
      by PHA-stimulated T-lymphocyte transformation. It was found that the RES
      functions were significantly depressed postoperatively and fairly recovered by
      the sixth postoperative day in the Fluosol-DA group. A prolongation of the
      suppression of cellular immunity with sustained fever was noted in this
      gastrectomized series. In analyzing the decay of infused Perfluolochemicals in
      blood, the half life of Fluorodecalin (FDC) was 4.9 +/- 0.1 hr, for
      Perfluorotripropylamine (FTPA) it was 5.1 +/- 0.1 hr. The prolonged depression of
      the RES function might be caused by saturation of RES with particles of
      Perfluorochemicals.

PMID- 15237300
TI  - Combined effects of succinylcholine and calcium on membrane-bound
      acetylcholinesterase activity.
AB  - The effects of succinylcholine and calcium (Ca2+), alone and together, on
      membrane-bound acetylcholinesterase ("true-type" cholinesterase) were examined
      using human erythrocyte ghosts to elucidate the combined pharmacological activity
      of succinylcholine and calcium in in vivo system. Succinylcholine inhibited the
      acetylcholinesterase by a mixed style. Calcium alone exhibited an inhibitory
      effect on the enzyme, but a biphasic effect together with succinylcholine: marked
      restoration of the enzyme activity at calcium concentrations lower than 6 mM and
      depression at its higher concentrations. It is suggested that calcium induces a
      conformational change of the enzyme protein leading to the altered binding
      capacity of succinylcholine. In anesthetic practice, therefore, the use of
      calcium may not be indicated for the treatment of SCh phase II block.

PMID- 15237301
TI  - The bioelectronic factors of human body fluids and intravenous replacement
      solutions.
AB  - In this paper the analytical method of the pH, rH2 and specific resistance of
      body fluids with B.E.-VINCENT Unit was described. From the values of the pH, rH2
      and specific resistance, other three bioelectronic factors, the redox potential,
      milliampere and micro-watts, were calculated. With this technique the
      bioelectronic factors of arterial and venous blood and urine obtained from 20
      young healthy adults were examined. Those of arterial and venous blood showed
      almost identical values. The urinary values of the pH, milliampere and microwatts
      varied as compared to those of blood. The bioelectronic factors of the various
      intravenous replacement solutions and blood components were considerably
      different from those of blood. It is considered that the bioelectronic factors of
      patient's blood should be checked repeatedly and maintained in an appropriate
      state when massive fluid therapy is required.

PMID- 15237302
TI  - Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in mice.
AB  - The effects of prolonged exposure to nitrous oxide on the hemopoietic progenitor
      cells in bone marrow and spleen in mice were investigated. Fifty percent nitrous
      oxide caused a marked decrease in the number of pluripotent stem cells (CFU-S)
      and granulocyte-macro-phage progenitor cells (GM-CFC) in the spleen, whereas it
      caused only a slight decrease in these cells in the bone marrow. These results
      suggest that prolonged exposure to nitrous oxide induces damage in the splenic
      hemopoiesis in mice.

PMID- 15237303
TI  - Clinical significance of mean circulatory filling pressure and cardiac preload
      under anesthesia.
AB  - The circulatory effects of a rapid infusion of plasma substitute with intravenous
      administration of nitroglycerine (TNG) were investigated in low pressure systems
      of anesthetized patients by measuring various hemodynamic parameters.
      Measurements were made when the systolic blood pressure reached 70-80% of the
      control value after intravenous administration of TNG at 1-2 microg/kg/min and a
      3.5% modified gelatin solution (Haemaccel) at a rate of 0.5 ml/kg/min. After the
      TNG was administered, the mean circulatory filling pressure (Pms) decreased, and
      the venous to arterial capacitance ratio (CV/CA) increased; however, they
      returned to control values after a rapid Haemaccel infusion. Changes in the
      pressure gradient between the X and Y valley of the right atrial pressure wave
      decreased to 70 +/- 14% of the control value when TNG was given and recovered to
      106 +/- 22% by infusion. Pulmonary vascular resistance (PVR) decreased to 70 +/-
      24% of the control value when TNG was administered and was restored to 96 +/- 40%
      by a rapid infusion. In the left ventricle, the mean velocity of myocardial
      circumferential fiber shortening (VCF) decreased in all cases when TNG was given
      and it recovered by a rapid infusion. In the right ventricle, VGF did not always
      decrease, and in a few case increased, but all cases recovered by a Haemaccel
      rapid infusion. We conclude that the augmentation of the right ventricular
      preload reserve is achieved by administration of TNG and infusion of a plasma
      substitute.

PMID- 15237304
TI  - Spread of epidural analgesia following a constant pressure injection--an
      investigation of relationships between locus of injection, epidural pressure and
      spread of analgesia.
AB  - (1) The spread of epidural analgesia following injection of 15 ml of 2%
      mepivacaine was 17.3 +/- 0.6, 14.3 +/- 0.4, and 13.3 +/- 0.7 spinal segments in
      cervical, thoracic, and lumbar epidural analgesia, respectively. The patient's
      age showed significant correlation with the spread of epidural analgesia in
      cervical (r = 0.5776, p < 0.001), thoracic (r = 0.3758, p < 0.01), and lumbar
      area (r = 0.8195, p < 0.001). The spread of cervical epidural analgesia was more
      caudad than cephalad (p < 0.05), but in lumbar epidural analgesia it was more
      cephalad than caudad (p < 0.05). There was no difference between the cephalad and
      caudad spread in thoracic epidural analgesia. (2) The epidural pressure
      immediately after injection of 15 ml of 2% mepivacaine into the lumbar epidural
      space at a constant pressure (80 mmHg) correlated to the patient's age (r = 
      0.5714, p < 0.001) and the spread of analgesia (r = -0.3904, p < 0.05). The lower
      epidural pressure associated with higher age, the wider spread of analgesia.
      There was no significant correlation between the residual pressure at 60 seconds
      and the age or the spread of analgesia.

PMID- 15237305
TI  - Response of blood cells to hemorrahagic shock in the dog.
AB  - Response of canine blood cells to hemorrhagic shock was examined using
      ultrastructural and ultracytochemical techniques. Blood platelets responded to
      hemorrhagic shock with a decrease of alpha-granules and the simultaneous
      development of the platelet canalicular system which opened to the extracellular
      environment, and platelets having no or few granules appeared at the end of the
      experimental period. Neutrophil leukocytes also responded to shock, with the
      decrease of both specific and azurophil granules. Eosinophil leukocytes were
      morphologically unchanged before and after shock but basophils were not found in
      the present observations. The effects of dexamethasone and phenoxybenzamine on
      inhibition of blood cell degeneration during hemorrhagic shock were examined.
      These drugs were considerably effective to inhibit degeneration of blood cells.

PMID- 15237308
TI  - Effects of thiopental on cardiac energy metabolisms in postischemic reperfusion
      in rat.
AB  - In experiments on isolated rat heart lung preparation, the effects of thiopental
      on myocardial metabolisms in postischemic reperfusion were evaluated with
      intramyocardial high energy phosphates, lactate, pyruvate and glycogen. The
      release of CPK in the perfusate blood was also measured at the end of
      reperfusion. After 10 min perfusion, hearts were made globally ischemic for 8 min
      and reperfused for 12 min. Large dose of thiopental (100 microg/ml) reduced the
      energy charge and glycogen content. Reperfusion with an anesthetic dose of
      thiopental (10 microg/ml) resulted in an exacerbation of the CPK release.
      Protection by thiopental during ischemia was not observed and its high dose may
      be harmful.

PMID- 15237306
TI  - Comparison of the epinephrine-induced arrhythmogenic effect of sevoflurane with
      isoflurane and halothane.
AB  - The effect of sevoflurane on cardiac arrhythmias induced by the infusion of
      epinephrine into dogs was compared with those of isoflurane and halothane. The
      arrhythmogenic doses of epinephrine determined in this comparative study were
      expressed by both infusion rates of epinephrine and the corresponding plasma
      levels obtained by a series of three-minute epinephrine infusions during
      sevolurane, isoflurane, and halothane anesthesia at 1.25 MAC. The mean values of
      the arrythmogenic infusion rates of epinephrine and the corresponding plasma
      levels were 17.3 microg/kg/min and 275.7 ng/ml for sevoflurane, 6.7 microg/kg/min
      and 149.2 ng/ml for isoflurane and 1.9 microg/kg/min and 39.1 ng/ml for
      halothane, respectively. These results indicate that the arrythmogenic doses of
      epinephrine during sevoflurane and isoflurane anesthesia were significantly
      higher than those during halothane anesthesia.

PMID- 15237307
TI  - CO2 rebreathing of T-piece system in patients during recovery phase from acute
      respiratory failure.
AB  - Eight respiratory parameters which might affect the amount of carbon dioxide
      rebreathing were assessed in seven patients who were breathing spontaneously from
      large-bore T tube system during the recovery phase from acute respiratory
      failure. With multivariate regression analysis, the absolute amount of rebreathed
      CO2 at the connector of endotracheal tube (VINSPCO2) were approximately estimated
      by using relatively small number of parameters, including minute volume (VEXP),
      fresh gas inflow to T piece system (VFGI) and preferably by additional parameters
      concerning CO2 output of the patients.CO2 rebreathing ratio, VINSPCO2 divided by
      gross outward flux of CO2 at the connector (VEXPCO2), was predicted with simple
      regression equation by using (VEXP/VFGI) as follows,(VINSPCO2)/(VEXPCO2) = 0.405
      + 0.33 x ln (VEXP/VFGI)The maximum (VEXP/VFGI) ratio to prevent rebreathing of
      CO2 at the connector was 0.30, whereas the ratio to prevent CO2 accumulation due
      to rebreathing was 0.45.

PMID- 15237309
TI  - Clinical study of glucose metabolism during partial gastrectomy--comparison
      between epidural and general anesthesia.
AB  - Plasma glucose, insulin, glucagon, growth hormone (GH) and cyclic-AMP (C-AMP)
      were measured in 14 patients undergoing partial gastrectomy under 5 g/hr glucose
      loading. Seven patients received general anesthesia (GOF; Group G) and the other
      seven, GO + epidural anesthesia (analgesia Th4-L1; Group E). Blood glucose
      increased in both groups, although it remained consistently lower in Group E than
      in Group G. Serum IRI and IRI/glucose ratio appeared consistently higher in Group
      E than in Group G and a significant difference was found between the two groups
      at the early period of surgery. The changes in plasma glucagon and GH were found
      independent of those in glucose. Cyclic-AMP was also consistently higher in Group
      G than in Group E and a significant difference was observed at the end of
      anesthesia. These results suggest that epidural anesthesia with 5 g/hr glucose
      loading may facilitate insulin release from the islet and peripheral blood uptake
      particularly during the early period of surgery while many other factors such as
      GH, cortisol and vagal stimulation seemed to be involved in the later period of
      surgery.

PMID- 15237310
TI  - Increased membrane fluidity of erythrocytes in a case with malignant
      hyperthermia.
AB  - In a case with malignant hyperthermia (MH), membrane fluidity of erythrocytes was
      studied by electron spin resonance (ESR)-spin labeling technique. The measurement
      was made with samples obtained during and after pyrexic crisis until full
      recovery. The results indicated that membrane fluidity increased during pyrexic
      crisis and that these changes were serially restored. As the physicochemical
      characteristics of the erythrocyte membrane resemble those of cellular and cell
      organella membrane, it was concluded that membrane composition and configuration
      might have been altered pathophysiologically during the crisis of MH in our case.

PMID- 15237311
TI  - Clinical experience of epidural fentanyl for labor pain.

PMID- 15237312
TI  - Anesthetic management for a patient with restrictive cardiomyopathy.

PMID- 15237313
TI  - Anaphylactoid reactions due to pancuronium.

PMID- 15237314
TI  - Anesthetic management of a patient with Crow-Fukase syndrome.

PMID- 15237315
TI  - Malignant hyperthermia associated with atypical central core disease.

PMID- 15237316
TI  - Bilateral pneumothorax, subcutaneous emphysema and pneumomediastinum under
      anesthesia.

PMID- 15237318
TI  - Dependence of the dose-response curve on incision site for intrathecal morphine.

PMID- 15237317
TI  - Anesthesia for a patient with total lipodystrophy--a clinical report.

PMID- 15237319
TI  - [Clinical performance measurement in surgery and orthopedics -- new aspects in
      2004].
AB  - In 2004, principles and practice of clinical performance measurement (CPM) in
      German hospitals were changed according to new legislative and administrative
      regulations. In many respects, focus and methods of clinical performance
      measurement were improved in favour of hospitals. Starting from January 1, 2004,
      the new Gemeinsamer Bundesausschuss (Joint Federal Board) has competence for
      decisions on future focus and scope of CPM. Former agreements on implementation
      of CPM in 2004 will be effective as long as Gemeinsamer Bundesausschuss passes
      new resolutions. Methods to identify relevant cases for CPM particularly changed
      in 2004. Until end of 2003, obligations to report case data were based on special
      types of hospital reimbursement. In 2004, obligations for reporting no longer
      derive from financial criteria, but from medical criteria such as diagnoses and
      procedures. In 2003, reporting for CPM covered more than 30 subjects in medicine
      and nursing. For 2004, the scope of CPM has been reduced by 13 subjects which
      need to be reconsidered in order to secure unified quality goals for out-patients
      as well as in-patients and to allow long-term follow-up of outcome data. For
      their CPM expenditure, hospitals receive an additional fee of euro 0.58 per case
      reimbursed by DRG. Financial sanctions will be effective for hospitals with
      overall CPM reporting rates below 80 %. Starting from 2005, hospitals are obliged
      to publish CPM reporting rates for each CPM subject in annual hospital quality
      reports.

PMID- 15237320
TI  - [Benefits and effectiveness of recording somatosensory evoked potentials in
      surgery on the carotid artery].
AB  - BACKGROUND: Operative treatment of high-grade carotid stenosis is an established
      procedure. The question whether a temporary - either selective or routine - shunt
      is needed, is a matter of controversy, and the decision is based on a number of
      available monitoring procedures. Within the framework of quality assurance based
      on the regular collection of our own patient data, carotid thromboendarterectomy
      (TEA) with recording of somatosensory evoked potentials (SEP) was analysed for
      its effectiveness. PATIENTS AND METHODS: Two non-randomised groups of patients
      were analysed retrospectively: Group I: 99 carotid TEAs with no recording of SEP
      (1.1.99-31.12.99); Group II: 139 carotid TEAs with SEP recording (1.1.01
      31.12.01). These two groups were unselected in terms of procedure, as also with
      regard to age, sex, stage or degree of carotid stenosis or surgeon, and were
      homogeneously distributed. A comparison was made of anaesthesia and operating
      times, shunt rate and the outcome of the two groups. Additionally, the two
      subgroups surgery with no shunt, and surgery with shunt, and the subgroups
      thromboendarterectomy with patchplasty (TEA) and eversion endarterectomy (EEA),
      were analysed. RESULTS: A temporary shunt was employed in 41 (41.4 %) of the
      patients in Group I (no SEP recording) and in 16 (11.5 %) of those in Group II
      (SEP recording). The average operating time in Group II was 11.4 min shorter (p <
      0.001) than in Group I. The average carotid clamping time in Group II was
      significantly reduced (by 4.2 min; p < 0.001), while the duration of anaesthesia
      prior to skin incision was increased by an average of 18.3 min (p < 0.001), and
      the overall duration of anaesthesia by an average of 15.8 min (p < 0.001). A
      comparison of the subgroups surgery with no shunt and surgery with shunt revealed
      - both in Group I and Group II - a significant prolongation of the anaesthesia
      time and operating time (p < 0.001). In both Groups I and II, the subgroup TEA
      revealed a significant prolongation of both the anaesthesia and operating times
      vis-a-vis EEA. The major stroke rate was 2.0 % in Group I and 1.4 % in Group II,
      and the minor stroke rate 3.0 in Group I and 3.6 % in Group II; no deaths were
      observed. CONCLUSIONS: A reduction in the shunt rate to 11 % (by means of SEP)
      significantly decreased the average operating time (incision - suture) and the
      clamping time, with identical outcome in Groups I and II. Despite a reduction in
      the average incision-suture time in Group II (with SEP recording), the average
      overall operating time (anaesthesia time) was significantly increased due to the
      greater technical effort required. Carotid TEA with a selective shunt as
      determined by SEP is a high-cost procedure with no demonstrable benefit. At a
      stroke rate < 5 % and a need for stratification into several groups in accordance
      with the AHA classification, it is not possible to achieve adequate patient
      recruitment for a randomised analysis of outcome of the individual monitoring
      procedures. Alternative procedures are the routine use of a shunt and operation
      under regional anaesthesia.

PMID- 15237321
TI  - [Impaired cerebral autoregulation in asymptomatic patients with carotid artery
      stenosis: comparison of acetazolamide-SPECT and transcranial CO(2)
      dopplersonography].
AB  - PURPOSE: The indication for operation in patients with asymptomatic high-grade
      carotid artery stenosis is still under debate. Since impaired cerebrovascular
      autoregulation is associated with an increased risk for ischaemic events,
      assessment of cerebral vascular reactivity might be a valuable selection
      criterion for surgery. The aim of our study was therefore to evaluate the
      incidence of impaired autoregulation in asymptomatic patients with acetazolamide
      single photon emission computed tomography (ACZ-SPECT) and transcranial CO (2)
      dopplersonography (CO (2)-TCD). Furthermore, both methods were compared in regard
      to results and clinical practicability. METHODS: In 42 patients with high-grade
      (> 70 %) asymptomatic carotid artery stenosis, cerebral perfusion and vascular
      reactivity were assessed with resting and ACZ-enhanced SPECT scans. In 31 of
      these patients the CO (2) reactivity of cerebral perfusion was determined by TCD
      and expressed as normalized autoregulation reserve (NAR). RESULTS: Cerebral
      perfusion was decreased in 14.3 %. In ACZ-SPECT 26 % and in CO (2)-TCD 28 %
      revealed an impaired vascular reactivity. Conformity of both methods was high
      (kappa = 0.93). TCD was superior in practicability, but only applicable in 81 %
      due to a missing temporal bone window for insonation. CONCLUSION: In accordance
      ACZ-SPECT and CO (2)-TCD could detect impaired vascular reactivity in a quarter
      of asymptomatic patients. Both TCD and SPECT could be of value for preoperative
      selection in this group of patients, whereby sonography is recommended for daily
      diagnostic work-up.

PMID- 15237322
TI  - [Penetrating aortic ulcer with severe gastrointestinal bleeding].
AB  - Primary aortointestinal fistula is a rare reason for gastrointestinal bleeding
      and mainly caused by a communication between the digestive tract and an aortic
      aneurysm. The penetrating aortic ulcer has been recently recognized as an
      independent pathological entity. It may penetrate through the aortic wall,
      leading to fistula into adjacent organs. We report the case of a 78-year-old
      woman who was admitted to our department with massive gastrointestinal
      hemorrhage. Endoscopy did not reveal the cause of hemorrhage. The diagnosis was
      made by computed tomography showing a primary aortoduodenal fistula without
      aortic aneurysm. The patient was successfully operated on. During urgent
      operation we found the penetrating atherosclerotic ulcer as the cause of the
      aortoduodenal communication. Primary aortoenteric fistula has a fatal outcome
      unless it is diagnosed accurately and urgently treated by surgical intervention.
      Contrast-enhanced computed tomography is the primary imaging modality to specify
      the diagnosis.

PMID- 15237323
TI  - [Intraoperative laparoscopic cholangiography -- when is it useful?].
AB  - Since the introduction of laparoscopic cholecystectomy (LC), a decrease in the
      practice of intraoperative cholangiography (IOC) has been reported. Are there
      actually reasons for carrying on IOC during LC? Depending on the management of
      common bile duct (CBD) stones treatment a different IOC regime is recommended. If
      the single-stage laparoscopic extraction of ductal calculi during LC is
      preferred, routine IOC is generally necessary to detect all CBD stones for
      desobstruction via ductus cysticus or choledochotomy. When therapeutic splitting
      is favoured, including two-stage management with endoscopic desobstruction and
      later LC, routine IOC can be foregone. However, selective practice of IOC can
      help to reduce the rates of unnecessary preoperative investigations from 40-60 %
      to 20 % when postoperative endoscopic desobstruction demonstrates similar success
      rates of about 95 %. Regarding the preventive character of laparoscopic IOC to
      CBD injuries, a routine investigation should be adopted by institutions with
      injury rates > 0.4 % and in the learning phase of young surgeons. For all other
      institutions a selective practice should be recommended when difficult
      intraoperative conditions render recognition of the anatomical situation more
      difficult or for identification of dissected non-bleeding ducts near the triangle
      of Calot.

PMID- 15237324
TI  - [Prophylactic splenectomy for splenic vein thrombosis in patients undergoing
      resection for chronic pancreatitis].
AB  - AIM: Chronic pancreatitis (CP) is the leading cause of splenic vein thrombosis
      (SVT). SVT occurs in about 15 % of patients with CP. The risk of variceal
      bleeding in SVT is approximately 10 %. Splenectomy is indicated in symptomatic
      SVT but its role in asymptomatic SVT is discussed controversially. Aim of our
      study was to evaluate the outcome of splenectomy performed during pancreatic
      resection in patients with CP and asymptomatic SVT. METHODS: 33 of 198 patients
      undergoing resection for CP underwent concomitant prophylactic splenectomy for
      asymptomatic SVT. Perioperative data were compared in the groups of patients with
      or without splenectomy. Follow-up was complete in 84 % (average 31 months).
      RESULTS: Median operative time, postoperative morbidity, reoperation rate and
      mortality were not different in patients with or without splenectomy. The median
      number of blood units transfused was higher in patients with prophylactic
      splenectomy (6 vs 4 units; p < 0.01). One complication of splenectomy
      (postoperative bleeding) occurred (3 %). During follow-up no variceal bleeding,
      no episode of postsplenectomy sepsis or thrombosis due to temporary
      thrombocytosis occurred. CONCLUSIONS: Complications of prophylactic splenectomy
      are rare and less frequent than reported episodes of variceal bleeding. In the
      presence of asymptomatic SVT splenectomy should be considered during pancreatic
      resection to facilitate surgery and to avoid further variceal bleeding.

PMID- 15237326
TI  - [Early results of laparoscopic surgical procedures in Crohn's disease].
AB  - INTRODUCTION: During the last years laparoscopic surgical procedures are used
      more frequently in benign bowel diseases like Crohn's disease. We are reporting
      early results of laparoscopic procedures in Crohn's disease at our hospital.
      PATIENTS AND METHOD: From 1994 to 2003 54 patients (20 male and 34 female)
      underwent laparoscopic colonic and small bowel surgery in Crohn's disease. The
      mean age was 32 years (range: 16 to 55 years). RESULTS: Complications occurred in
      6 patients (11.1 %). 3 patients needed a laparotomy. One computed tomography
      puncture was performed due to a hematoma. The remaining patients are treated
      successfully non-operatively. No patient died during the perioperative period.
      The mean operating time was 152 minutes (range 35 to 360 minutes) and the mean
      postoperative stay in hospital was 10 days (range 6-35 days). 0.2 blood cell
      concentrates were needed per operation (range 0 to 6), on average. The patients
      needed no analgesics after the 5 (th) day (range 1 to 13 days), got liquid diet
      on the 2 (nd) (range 0 to 6 days) and solid diet on the 3 (rd) day after surgery
      (range 1 to 14 days). DISCUSSION: Laparoscopic surgery in Crohns disease is safe
      when performed by an experienced surgeon. The laparoscopic procedure results in a
      better cosmetic result, while the longer operating time is the mean disadvantage.
      There are low complication rates during the early postoperative period.

PMID- 15237327
TI  - [Transanal staplermucosectomy for symptomatic rectocele with outlet obstruction].
AB  - Between 1.1.2001 and 30.6.2002 n = 52 female patients with symptomatic isolated
      anterior rectocele underwent transanal staplermucosectomy. All of them were
      suffering from outlet obstruction. In addition 9 patients complained incontinence
      grade I and n = 1 incontinence grade III. Complete colonoscopy, defecography and
      combined anal manometry with needle EMG were carried out preoperativly for
      exclusion of synchronous pathological findings. Sphinctermanometry showed a
      significant lower preoperative resting pressure (p < 0.01, t-test ) of 77.0 +/-
      21.0 cm H (2)O in comparison to a normal collective. Surgical procedure consisted
      in a modified staplerresection of the rectocele area with tightening of the
      anterior rectal wall. No intraoperative complications occurred and outlet
      obstruction disappeared in all patients. Further investigations have to be
      performed to show long-term effects of this procedure.

PMID- 15237325
TI  - [Is the pneumoperitoneum minimally invasive during laparoscopic colonic
      surgery?].
AB  - The importance of laparoscopic colonic surgery has increased considerably in the
      past decade. However, a minimally invasive operation with induction of
      pneumoperitoneum does not imply a minimally invasive anaesthesia. The
      haemodynamic effects of intraperitoneal carbon dioxide insufflation depend an the
      extent of intraabdominal pressure elevation, severity of preexisting
      cardiopulmonary diseases, alterations of arterial PCO (2) and pH, volume state of
      the patient and co-medications. In addition, positioning of the patient for
      laparoscopic colonic surgery and endocrinological reactions during and after
      induction of pneumoperitoneum may significantly affect systemic and pulmonary
      haemodynamics. Intraabdominal operations may impair respiratory function
      independent from anaesthesia. Preoperative evaluation of the high risk patient is
      of utmost importance. Assessment of expiratory PCO (2), extended cardiopulmonary
      monitoring and maintenance of intraabdominal pressure in the range of 5 - 7 mmHg
      are recommended during laparoscopic colonic surgery.

PMID- 15237328
TI  - [Hemorrhoid Therapy with Doppler Guided Hemorrhoidal Artery Ligation via
      Proctoscope KM-25. A New Alternative to Hemorrhoidectomy and Rubber Band
      Ligation?].
AB  - The aim of treating patients suffering from hemorrhoids is to eliminate or to
      relieve their complaints. The method should be performed on an out-patient basis,
      and should be painless and low rated concerning complications. The Morinaga
      technique fulfills these conditions, its feasibility and the results in 281
      patients are presented.

PMID- 15237329
TI  - [Effect of biofeedback and electrostimulation on sphincter function in fecal
      incontinence].
AB  - The following study reports on the effect of biofeedback and transanal electric
      stimulation as a conservative method in the therapy of idiopathic fecal
      incontinence. 22 consecutive patients in whom the diagnosis "idiopathic
      incontinence" was established after endoscopy, endoanal ultrasound and
      measurement of pudendal nerve terminal motor latency underwent combined sphincter
      training for 3 months. The results were evaluated prospectively by clinical
      classification using a modified Kelly-Holschneider-score and anal manometry
      before and after treatment. Combined biofeedback led to a significant increase of
      the continence score in 18 of 22 patients (7.7 +/- 3.8 vs. 9.3 +/- 3.0, p =
      0.004). Both squeeze (77 +/- 28 mmHg vs. 92 +/- 32 mmHg, p = 0.047) and resting
      pressures (40 +/- 19 vs. 52 +/- 23 mmHg, p = 0.015) increased significantly
      during the training period. There were no significant differences in squeeze and
      resting asymmetry indexes, sensory and urge thresholds and maximal tolerable
      volumes. The prolongation of biofeedback training from 3 to 6 months in 9
      patients did not change clinical or manometric results significantly.
      CONCLUSIONS: The combination of biofeedback training with anal electrostimulation
      increases anal squeeze and resting pressures, thus leading to an improvement of
      clinical incontinence symptoms. Therefore it should be the first choice in the
      therapy of idiopathic fecal incontinence. A training period of 3 months seems to
      be sufficient.

PMID- 15237330
TI  - [Pilonidal Sinus -- Primary Closure also in Case of Abscess?].
AB  - After excision of pilonidal sinus treatment consists either in open procedure or
      primary closure. We present the results of 45 consecutive patients (male 29,
      female 16, age 32 +/- 13 years), who underwent surgery between September 2001 and
      December 2002. Fourteen patients had simple fistula without infection, 18 had
      fistulas with putride secretion and 13 had abscess. Primary closure with direct
      suture was performed in 34 patients (76 %: 13 x simple fistula, 13 x fistula with
      putride secretion, 8 x abscess). Eleven patients were treated by layopen
      procedure and secondary wound healing. Wound infection occurred in 13 patients (7
      x superficial, 6 x deep). Mean time of postoperative treatment was 15 +/- 3 days
      after closure and primary healing and 66 +/- 15 days after open proce dure or
      secondary healing. Mean time out of work was 19 +/- 10 respectively 52 +/- 19
      days. A recurrence of fistula occurred in eight patients after primary closure
      (18 %) and none after open procedure. Also in cases of pilonidal sinus with
      infection, primary wound closure can be carried out even though the rate of
      recurrences is higher than after open procedure. A successful primary closure
      significantly reduces time of illness and time out of work.

PMID- 15237332
TI  - [Surface characterisation of shot peened implants with glas beads in total hip
      arthroplasty].
AB  - Alumina-blasting is used to create a rougher surface of Titanium implants in
      cementless total hip arthroplasty to achieve a better bony ingrowth. An
      increasing number of publications in maxillofacial surgery and orthopaedic
      surgery show that there is a significant contamination in Alumina blasted
      surfaces. Latest research published an effect of contaminant particles on early
      loosening of endoprostheses associated with third body wear. Due to our knowledge
      no previous study analysed surface contamination of hip endoprostheses with glass
      beads. Aim of our work was to evaluate the percentage of contaminated surface of
      hip endoprostheses with glass beads. MATERIAL AND METHOD: The surface of 5 Ti-VPS
      sprayed Phoenix cups and 5 morse-taper-junctions of the MRP-Titan revision stem
      (Peter Brehm, Chirurgie Mechanik, Weisendorf) were analysed with respect to glass
      particles. Shot peening was performed with glass beads "BALLOTINI" MGL, Fa. Wurth
      Strahlmittel. A field emission scanning electron microscopy (LEO 1525) was used
      for the detection of the glass-particles on the implant surface with a
      backscattered electron detector. The particle covering position was calculated by
      means of an imaging analyze software (analySIS, Soft Imaging System GmbH).
      RESULTS: The surface of the Ti-VPS sprayed Phoenix cups showed a contaminated
      area at a mean of 9.2 +/- 1.3 %, morse-taper-junctions of the MRP-Titan stem at a
      mean of 9.6 +/- 2.1 % with glass particle contact. DISCUSSION: The results of
      this study clearly show that there is a contamination of shot pinned Titanium
      surfaces with glass particles in a significant percentage. With respect to third
      body wear in total hip arthroplasty further studies are necessary to minimize
      contamination.

PMID- 15237331
TI  - [Mitigated erysipelas after implantation of foreign material].
AB  - When an infection occurs in the incisional area following surgery where foreign
      materials (i. e. endoprostheses, metal plates or plastic meshes) are implanted, a
      revision may become necessary because an infection in the area of the implant and
      involvement of the implant itself cannot be ruled out. In the case of a mitigated
      erysipelas, cultures taken during the revision seldom show bacterial growth. The
      disease progresses because surgery does not solve the problem of a weakened
      immune system and lymph stasis; on the contrary, it usually deteriorates the
      situation. A high dose antibiotic regimen is recommended as therapy for the
      mitigated erysipelas instead of an operative revision orally given. levofloxacin
      has proven to be successful reducing the recurrence rate. The course of two
      patients with mitigated erysipelas is represented for example in form of case
      studies. The patients were underwent several surgical revisions. But we had not
      to explant the endoprostheses at all. Finally both patients were treated with
      levofloxacin without further relapses.

PMID- 15237333
TI  - [Legal risks of surgeons infected with hepatitis B, C or HIV virus].

PMID- 15237334
TI  - [Interventionel MRT: current inventory and preview].

PMID- 15237335
TI  - [Long-term central venous lines and their complications].
AB  - The implantation of permanent (> 14 days) central venous catheters is constantly
      increasing, accelerated by a trend toward outpatient therapies. Subcutaneous
      tunneled and non-tunneled catheters as well as port systems are available. The
      interventional radiologist plays an important role in the implantation of central
      venous catheters as well as in detection and treatment of any complications.
      Various access ways via peripheral and central veins are described and the
      implantation techniques for the different systems explained. The use of peel-away
      sheaths allows the radiologist to implant subcutaneous tunneled catheters via the
      Seldinger technique without surgical preparation. Procedure-related early and
      late complications may occur, and the radiologist plays an important role in the
      surveillance and management of catheter-associated complications. This review
      demonstrates the different catheter systems and implantation techniques.

PMID- 15237336
TI  - Diagnostic performance of a commercially available computer-aided diagnosis
      system for automatic detection of pulmonary nodules: comparison with single and
      double reading.
AB  - OBJECTIVE: To assess the diagnostic performance of a commercially available
      computer-aided diagnosis (CAD) system for automatic detection of pulmonary
      nodules with multi-row detector CT scans compared to single and double reading by
      radiologists. MATERIALS AND METHODS: A CAD system for automatic nodule detection
      (Siemens LungCare NEV VB10) was applied to four-detector row low-dose CT (LDCT)
      performed on nine patients with pulmonary metastases and compared to the findings
      of three radiologists. A standard-dose CT (SDCT) was acquired simultaneously and
      used for establishing the reference data base. The study design was approved by
      the Institutional Review Board and the appropriate German authorities. The
      reference data base consisted of 457 nodules (mean size 3.9 +/- 3.1 mm) and was
      established by fusion of the sets of nodules detected by three radiologists
      independently reading LDCT and SDCT and by CAD. An independent radiologist used
      thin slices to eliminate false positive findings from the reference base.
      RESULTS: An average sensitivity of 54 % (range 51 % to 55 %) was observed for
      single reading by one radiologist. CAD demonstrated a similar sensitivity of 55
      %. Double reading by two radiologists increased the sensitivity to an average of
      67 % (range 67 % to 68 %). The difference to single reading was significant (p <
      0.001). CAD as second opinion after single reading increased the sensitivity to
      79 % (range 77 % to 81 %), which proved to be significantly better than double
      reading (p < 0.001). CAD produced more false positive results (7.2 %) than human
      readers but it was acceptable in clinical routine. CONCLUSION: Double reading
      with CAD as second reader offered a significantly increased sensitivity compared
      to conventional double reading. Thus, CAD is a valuable tool for the detection of
      pulmonary nodules and should be used as second opinion.

PMID- 15237337
TI  - [Humeroradial plica: frequency and visualization on MRI].
AB  - PURPOSE: To determine frequency and size of a humeroradial plica and correlate it
      with degenerative changes, and to determine frequency of the visualization of a
      synovial fold on MR-Images (T1-weighted spin-echo and STIR sequences) and
      correlate it with degenerative changes. MATERIALS AND METHODS: Forty-two elbow
      specimens were dissected and studied for humeroradial synovial folds (small,
      medium, large) and degenerative changes (absent, medium, strong), and 88 elbow MR
      images were analyzed for a synovial fold (not visible, small, large) and
      degenerative changes (absent, medium, strong). Comparison was performed using the
      chi (2) test. RESULTS: Dissections revealed a synovial fold in all cases. The
      sizes were small in n = 13 (31 %), medium in n = 24 (57 %), and large in n = 5
      (12 %). Degenerative changes were absent in n = 9 (21.4 %), medium in n = 29 (69
      %), and strong in n = 4 (9.6 %). On MRI the synovial fold was not visible in n =
      67 (76 %), small in n = 12 (14 %), and large in n = 9 (10 %). Degenerative
      changes on MRI were absent in n = 65 (74 %), medium in n = 15 (17 %), and strong
      in n = 8 (9 %). The size of the fold correlated positively with degenerative
      changes in the specimen but not with degenerative changes on MRI. The T1-SE
      sequence was superior to the STIR sequence in revealing the synovial fold.
      DISCUSSION: A humeroradial plica is a regular finding, but visualized by MRI in
      only approximately 20 %, probably due to its variable size. Its visualization
      succeeds best with T1-spin-echo sequences.

PMID- 15237338
TI  - [Rhabdoid tumors of the kidney in childhood].
AB  - PURPOSE: The primary diagnosis of renal masses in children is made by imaging
      studies. This retrospective analysis describes the imaging features of rhabdoid
      tumors (RT) with US, CT and MRI, to point out characteristics and to evaluate the
      possibility of differentiation between RT and Wilms tumor. MATERIALS AND METHODS:
      We reviewed 10 MRI (6 STIR, 9 T1 w, 8 T2 w, 10 T1 post KM), 15 CT (9 Nativ-CT, 14
      KM-CT) and 14 US images of 22 patients (age 2 - 57 months) with
      histopathologically confirmed RT. The following characteristics were evaluated:
      subcapsular fluid collection, multiple tumor lobules, presence of calcification,
      primary tumor size, visibility of tumor margin, tumor necrosis and metastases.
      RESULTS: The mean total tumor volume was 238 ml. 19 RT were located in the
      perihilar/medullary region with invasion of the renal hilum, and 5/22 tumors
      showed multiple tumor lobules. Subcapsular fluid collection was found in 6/22
      cases. Calcifications were present in 6/19. Eleven tumors were well defined from
      the renal parenchyma, 9 poorly defined, 2 could not be assessed. In 19/22 cases
      tumor necrosis was found. Distant metastases were seen in 8 cases in the lung, in
      3 cases in the CNS. Metastases of regional lymph nodes were seen in 9 cases.
      CONCLUSION: The evaluated characteristics frequently found in RT are not
      indicative of these tumors. RT cannot clearly be differentiated from Wilms tumor
      by imaging studies. Because of frequent involvement of the CNS and lung, a MRI of
      the CNS and CT of the lung is indicated after histopathologic diagnosis of RT is
      made.

PMID- 15237339
TI  - [Imaging characteristics of childhood lipoblastoma].
AB  - PURPOSE: Lipoblastoma and lipoblastomatosis are very rare benign neoplasms, which
      almost exclusively occur in infants and young children. Despite their potential
      to local invasion and rapid growth, these tumors have an excellent prognosis,
      particularly if resected completely. Usually, the diagnosis is not taken into
      consideration preoperatively, and depends on histopathological evaluation. This
      study was done to determine imaging characteristics of lipoblastoma. MATERIALS
      AND METHODS: Eight cases of histopathologically proven lipoblastoma treated from
      1988 to 2003 were reviewed, comprising four girls and four boys ranging in age
      from 17 months to nine years. The localization was chest wall (four times),
      abdominal wall (once), gluteal region (once), lower leg (once) and forearm
      (once). Ultrasound, MRI and CT scans were evaluated and correlated to clinical
      data of the patients. RESULTS: Ultrasound showed lipomatous echogenicity and
      echotexture. The tumors appeared signal intensive on T1-weighted MR images and
      had a mean intensive signal on T2-weighted MR images with fat suppression. They
      were markedly hypodense on CT. The growth pattern was invasive in all imaging
      methods, with extension into preformed spaces, such as intercostal spaces and
      neural foramina, but without infiltration into surrounding structures or
      metastases. CONCLUSION: Ultrasound and MRI are the methods of choice to diagnose
      lipoblastoma by revealing structures and local growth pattern that appear
      specific of this rare tumor entity. The imaging characteristics of the
      lipoblastoma have to be correlated with the age of patients to exclude other
      conditions in the differential diagnosis.

PMID- 15237340
TI  - [Indirect MR venography: contrast medium protocols, postprocessing and
      combination in diagnosing pulmonary emboli with MRI].
AB  - PURPOSE: Integration of MR venography in a comprehensive MR imaging protocol in
      patients with suspected pulmonary embolism (PE) and evaluation of contrast media
      dosage, timing and postprocessing for diagnostic accuracy. MATERIALS AND METHODS:
      Forty-eight consecutive inpatients with suspected PE or deep vein thrombosis were
      examined by MR venography according to one of the following protocols: protocol
      I: MR venography only, 0.25 mmol/kg body weight (BW) Gadopentate dimeglumine (Gd
      DTPA) as single dose, bolus timing; protocol II: MR angiography of pulmonary
      arteries with a cumulative dosage of 0.25 mmol/kg contrast media, modification of
      coil setting for MR venography without further contrast media application;
      protocol III: as protocol II but with 0.125 mmol/kg BW, followed by MR
      venography. Signal-to-noise ratio, contrast-to-noise ratio, number of definable
      vascular segments and image quality were evaluated. The results were compared to
      conventional bilateral venography. RESULTS: All MR venography examinations were
      of diagnostic quality and the examination time was below 10 min. MR venography
      could be performed in all 48 patients compared to 43 of 48 patients for
      conventional venography. Significantly more superficial and deep veins of the leg
      could be visualized by MR venography (94 % compared to 83 % for conventional
      venography). Sensitivity and specificity were 100 % and 92 %, respectively.
      Quality differed significantly between 0.125 mmol/kg (protocol III) and 0.25
      mmol/kg Gd-DTPA (protocols I and II) while timing did not influence quality
      (protocol I vs. II). CONCLUSION: An integrated MR diagnostic evaluation of
      pulmonary arteries and veins of the leg is feasible in patients with suspected
      PE. MR venography with 0.25 mmol/kg Gd-DTPA reliably depicts the venous system of
      the leg more completely than conventional venography with at least equivalent
      diagnostic confidence.

PMID- 15237341
TI  - [Comparison of contrast-enhanced MR angiography of the aortoiliac vessels using a
      1.0 molar contrast agent at 1.0 T with intra-arterial digital subtraction
      angiography].
AB  - PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced MR angiography
      (CE-MRA) using a 1.0 molar contrast agent at 1.0 T for the diagnosis of abdominal
      aortic aneurysms and stenoses of renal or iliac arteries in comparison to
      intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: A
      total of 19 patients with the suspicion of abdominal aortic aneurysm or stenosis
      of renal or iliac arteries were examined with CE-MRA at 1.0 T. Intra-arterial DSA
      served as reference in all cases. After test bolus tracking, 10 or 8 ml of the
      1.0 molar contrast agent Gadobutrol corresponding to a dose of 0.1 - 0.15 mmol/kg
      bw were injected and imaging performed using a FLASH-3D sequence. To evaluate the
      interobserver-variability, the blinded images were analyzed by two radiologists.
      Besides the rating of overall image quality on a 4-point-scale, the images were
      evaluated for aneurysms and arteriosclerotic lesions with a stenosis of < 50 % or
      > 50 % or occlusion. RESULTS: A total of 144 segments were analyzed. The mean
      value of the CE-MRA image quality was 3.4 on a 4-point-scale. The sensitivity of
      CE-MRA in depicting relevant pathological findings was 96 % and the specificity
      99 %. The positive predictive value was 96 % and the negative predictive value 99
      %. Inter-observer variability was low with a kappa value of 0.82. CONCLUSION: CE
      MRA using a 1.0 molar contrast agent at 1.0 T enables an excellent diagnosis or
      exclusion of pathologies of the aortoiliac vessels.

PMID- 15237342
TI  - [Long-term hemodynamic compromise in internal carotid artery dissection:
      quantitative blood volume flow evaluation using 2D Cine phase-contrast MR
      imaging].
AB  - PURPOSE: To use the magnetic resonance (MR) phase-contrast technique as a non
      invasive method to determine blood volume flow in internal carotid artery (ICA)
      dissection, which has variable initial volume flow reduction and long term
      hemodynamic compromise. ICA dissection can lead to partial or complete
      recanalization or persistent occlusion, and strong clinical motivation exists for
      reliable assessment of the blood flow, in particular blood volume flow, in the
      carotid artery circulation after ICA dissection. MATERIALS AND METHODS: Blood
      volume flow in the carotid artery circulation was quantified in 28 patients with
      unilateral ICA dissection and 20 age-matched normal controls. Blood volume flow
      was measured in the ICAs and the common carotid arteries (CCAs) using 2D cine
      phase-contrast MR imaging. Final measurements were performed until after at least
      6 months the hemodynamic compromise showed no changes by ultrasound and MRA.
      RESULTS: In long term follow up, 11/28 patients demonstrated remaining vessel
      occlusion, 10/28 partial and 7/28 complete recanalizations. Patients with ICA
      occlusion showed a significant contralateral volume flow increase (mean 56 %, p <
      0.001) in comparison to normal controls. Patients with partial recanalization
      demonstrated volume flow rates between 24 ml/min and 188 ml/min in the dissected
      ICA and a less but significant (p < 0.001) increase in the contralateral volume
      flow. In patients with complete recanalization, normal volume flow conditions
      were found for both ICAs and CCAs. CONCLUSION: In ICA dissection, quantitative
      volume flow determination using 2D cine phase-contrast MR imaging is helpful in
      the initial assessment and long term follow-up of hemodynamic compromise. ICA
      dissection demonstrated a partial or complete recanalization in nearly (2/3) of
      the investigated patients and a persisting vessel occlusion in little more than
      (1/3). Compensatory contralateral increase in volume flow was found.

PMID- 15237344
TI  - [Evaluation of percutaneous vertebroplasty in osteoporotic vertebral fractures
      using a combination of CT fluoroscopy and conventional lateral fluoroscopy].
AB  - PURPOSE: Evaluation of vertebroplasty using a combination of CT-fluoroscopy and
      conventional lateral fluoroscopy in patients with osteoporotic vertebral
      fractures. MATERIALS AND METHODS: Fifty-eight patients (23male, 35 women, age
      69.7 +/- 10.2 years) with painful osteoporotic vertebral fractures were treated
      with vertebroplasty in conscious sedation and local anesthesia. Spiral-CT with
      sagittal reconstructions of the respective vertebral bodies was used for
      classification of the fracture. The cannula was placed under CT-guidance in the
      ventral third of the respective vertebral bodies and cement instilled under CT
      fluoroscopy and lateral fluoroscopy. When cement migrated towards the vertebral
      canal, the injection was immediately stopped for 30 - 60 seconds. After
      polymerization in this location, the injection was continued until sufficient
      filling of the vertebra. Results were documented by spiral CT with sagittal
      reconstructions. RESULTS: A total of 123 vertebral bodies were treated,
      comprising 39 thoracic and 84 lumbar vertebral bodies, with a mean of 2.1 +/- 1.3
      (range 1 to 6) vertebral bodies in each patient and a maximum of 3 vertebral
      bodies per session. All interventions were successfully completed in conscious
      sedation and local anesthesia. A mean volume of 5.9 +/- 0.6 ml (range 2 to 14 ml)
      cement was applied for each vertebra, with 79.7 % of procedures performed using a
      unilateral access. To achieve a sufficient cement deposit, a bilateral access was
      used in 20.3 %. The dorsal wall of the vertebra was included in 23.6 % of the
      fractures. In one case, cement migration into the spinal canal was detected,
      reducing the diameter of the canal by 30 %. In two other cases, cement leakage
      was seen at the puncture site of the vertebra (one intercostotransversally in the
      10 (th) thoracic vertebra and one dorsolaterally in the 1 (st) lumbar vertebra)
      with retrograde cement migration through the neuroforamen into the epidural
      space. In one of these cases, the cannulation of the vertebra had been changed
      before cement application resulting in a hole in the dorsolateral vertebral wall.
      However, all patients were discharged without evidence of neurologic
      complications. Multiplanar reconstructions of CT scans were used for the
      detection of extraosseous cement leaks: The incidence of extraosseous cement
      leaks was 4.1 % in epidural veins, 6.5 % in paravertebral vessels (6 veins, 2
      arteries), and 17.9 and 11.4 %, respectively, for upper or lower end plates. At
      discharge, 25 patients (43.1 %) were free of pain and 28 (48.3 %) significantly
      improved with a considerable reduction of analgetic drugs. Significant complaints
      persisted in 5 patients (8.6 %) with concomitant degenerative disease in four and
      vasculitis in one case. CONCLUSION: Percutaneous vertebroplasty is effective for
      stabilization and pain management of osteoporotic vertebral fractures. The
      procedure can be safely performed in conscious sedation and local anesthesia.
      Compared to conventional fluoroscopy alone, CT fluoroscopy provides an excellent
      additional monitoring of the procedure and probably contributes to the safety of
      the procedure.

PMID- 15237343
TI  - [Three-dimensional digital rotation angiography for embolization therapy of
      uterine leiomyomas: first results].
AB  - PURPOSE: To evaluate three-dimensional rotational digital subtraction angiography
      (3D-RDSA) in the embolization of the uterine artery in the treatment of
      symptomatic uterine leiomyomas (fibroids). MATERIALS AND METHODS: Eight women
      with complex pelvic vessel anatomy caused by large fibroids were embolized using
      3D-RDSA. The raw data were sent to an external workstation, and video files with
      a resolution of one image/3 degrees and a scan range of 180 degrees in a surface
      shaded display mode were produced. The primary goal was to assess an image
      intensifier angulation for the optimal visualization of the origin of the uterine
      artery. In addition, the intervention parameters were compared with those of 48
      patients with standard angiography. RESULTS: The analysis revealed no single
      angulation that can be recommended for standard angiography. No statistical
      differences were found between both groups concerning fluoroscopy time, dosage
      area product and amount of administered contrast medium (p > 0.05). CONCLUSION:
      It can be stated that 3D-RDSA is a feasible method that facilitates the
      catheterization of the uterine artery even in patients with complex pelvic vessel
      anatomy, with the potential to reduce the radiation exposure and the amount of
      administered contrast medium in future embolization therapy of symptomatic
      uterine fibroids.

PMID- 15237346
TI  - [Multislice spiral CT (MSCT) in pediatric radiology: dose reduction for chest and
      abdomen examinations].
AB  - The advent of multislice spiral CT (MSCT) technique has led to new aspects of
      dose reduction, especially for the dedicated use of MSCT in children. Optimizing
      pediatric MSCT protocols according to the clinical problem allows reduction of
      radiation exposure to a minimum without loss of diagnostic quality. The different
      parameters that influence the degree of dose reduction, like tube current-time
      product (mAs), tube voltage (kV), collimation and pitch, are discussed in context
      with previously published data and our own experience in nearly 200 pediatric CT
      examinations. In our department, the effective mAs is calculated for a pediatric
      chest MSCT by multiplication of the body weight in kilogram with a factor of 1 to
      1.5 and for a pediatric abdominal MSCT by multiplication with a factor of 2 to
      2.5. To calculate the equivalent effective dose for a contrast media-enhanced 80
      kV protocol, the effective mAs of the 120 kV protocol can be multiplied by 2.7. A
      factor less than 2.7 means further dose reduction. Compared to the radiation
      exposure with a standard adult protocol, the effective dose in a pediatric
      thoracic MSCT could be reduced by up to 92 % in neonates, 89 % in toddlers and 80
      % in school children. In abdominal MSCT, the effective dose could be reduced by
      up to 90 % in neonates, 89 % in toddlers and 83 % in school children. Using an
      adequate MSCT technique in children by adjusting the CT scanning parameters to
      the clinical question and body weight of the examined child enables a significant
      reduction of radiation exposure in comparison to standard MSCT protocols.

PMID- 15237347
TI  - [Evaluation of the display quality of different modalities in digital radiology].
AB  - PURPOSE: To evaluate the display quality of digital radiographies on different
      monitors in comparison to hard-copy films on view boxes. MATERIALS AND METHODS:
      Radiographs of different statistical phantoms simulating common pathologies of
      the chest, such as interstitial pneumonia, pneumothorax and pulmonary nodules,
      were acquired. Under same ambient light condition, the radiographs were rated as
      to the presence or absence of a simulated pathological finding using a confidence
      scale. The evaluation was performed on a grey-scale monitor, a color monitor, two
      LC displays and two different light boxes by four experienced radiologists.
      Sensitivity and specificity were determined in a ROC analysis for each viewing
      modality and phantom. The area under the curve (Az) was acquired cumulatively
      including the results of all investigators. A total of 4200 rating decisions were
      included. The chi (2)-test was performed for significance analysis using the a
      and b parameters of two ROC-curves (alpha = 0.05). RESULTS: The rating of the
      included LC displays (Az = 0.7009 - 0.9608) and color monitors (Az = 0.7993 -
      0.9591) showed a significant loss of diagnostic validity in comparison to the
      grey-scale monitor (Az = 0.8435 - 0.9762) and the view boxes (Az = 0.8228 -
      0.9891). CONCLUSION: LC displays and color monitor included in this study cannot
      be recommended for diagnostic viewing. The loss of diagnostic validity might be
      attributable to the viewing-angle-dependent contrast of LC displays. However, no
      loss in diagnostic validity could be assessed for the tested grey-scale monitor.

PMID- 15237345
TI  - [First clinical experience with extended planning and navigation in an
      interventional MRI unit].
AB  - PURPOSE: To present an advanced concept for patient-based navigation and to
      report on our first clinical experience with interventions in the cranium, of
      soft-tissue structures (breast, liver) and in the musculoskeletal system.
      MATERIALS AND METHODS: A PC-based navigation system was integrated into an
      existing interventional MRI environment. Intraoperatively acquired 3D data were
      used for interventional planning. The information content of these reference data
      was increased by integration of additional image modalities (e. g., fMRI, CT) and
      by color display of areas with early contrast media enhancement. Within 18
      months, the system was used in 123 patients undergoing interventions in different
      anatomic regions (brain: 64, paranasal sinus: 9, breast: 20, liver: 17, bone: 9,
      muscle: 4). The mean duration of 64 brain interventions was compared with that of
      36 procedures using the scanner's standard navigation. RESULTS: In contrast with
      the continuous scanning mode of the MR system (0.25 fps), the higher quality as
      well as the real time display (4 fps) of the MR images reconstructed from the 3D
      reference data allowed adequate hand-eye coordination. With our system, patient
      movement and tissue shifts could be immediately detected intraoperatively, and,
      in contrast to the standard procedure, navigation safely resumed after updating
      the reference data. The navigation system was characterized by good stability,
      efficient system integration and easy usability. Despite additional working steps
      still to be optimized, the duration of the image-guided brain tumor resections
      was not significantly longer. CONCLUSION: The presented system combines the
      advantage of intraoperative MRI with established visualization, planning, and
      real time capabilities of neuronavigation and can be efficiently applied in a
      broad range of non-neurosurgical interventions.

PMID- 15237348
TI  - [Diagnostic imaging in polytrauma: comparison of radiation exposure from whole
      body MSCT and conventional radiography with organ-specific CT].
AB  - PURPOSE: To compare the radiation dose of whole-body multislice CT (MSCT) and
      conventional radiography with organ-specific CT in polytrauma. MATERIALS AND
      METHODS: The whole-body MSCT encompassing brain, neck and midface, chest, abdomen
      and pelvis was performed on a Somatom Volume Zoom (Siemens). Conventional
      radiography consisted of chest and cervical, thoracic and lumbar spine in two
      views as well as pelvis (Polymat, Siemens). Three combinations of organ specific
      CT were chosen: CT examination of (1) head and cervical spine, (2) head, cervical
      spine and chest, (3) head, cervical spine and abdomen. The effective doses of
      whole-body MSCT and conventional radiography with organ-specific CT were
      calculated. RESULTS: Effective doses were 20 mSv for whole-body MSCT, 2 mSv for
      conventional x-ray, and 5 mSv for combination (1), 8 mSv for combination (2) and
      (3) 16 mSv for combination (3) of the organ-specific CT. The ratio of radiation
      dose between whole-body MSCT and radiography was 10 : 1. This ratio was reduced
      to 3 : 1, 2 : 1 and 1 : 1 when a combination of radiography and CT was performed.
      CONCLUSIONS: Whole-body MSCT in polytrauma compared to conventional radiography
      with organ-specific CT induces a threefold increased dose in unfavorable
      situations and no increased dose in favorable situations. Nevertheless, routine
      use of whole-body MSCT should be critically evaluated and should be adapted to
      the clinical benefit.

PMID- 15237349
TI  - [Pigmented neurofibroma of the basal skull].

PMID- 15237350
TI  - [Outcome of a cysto-ventriculostomy using 3D-constructive interference in steady
      state MRI].

PMID- 15237351
TI  - [Invasive actinomycosis in a patient with ten year intrauterine polyps].

PMID- 15237352
TI  - [Aortocaval fistula in an abdominal aortic aneurysm].

PMID- 15237354
TI  - Free fillet flap of the hand for elbow preservation in nonreplantable forearm
      amputation.
AB  - The use of non-replantable amputated parts for reconstruction of the stump is a
      well-established technique. The use of a free fillet flap of the hand and forearm
      for elbow preservation in massive trauma of the upper extremity is reported in
      two cases. These free flaps allowed for covering and preserving a functional
      elbow and a more useful stump.

PMID- 15237353
TI  - New one-stage nerve pedicle grafting technique using the great auricular nerve
      for reconstruction of facial nerve defects.
AB  - A new one-stage nerve pedicle grafting technique, employing a vascularized great
      auricular nerve graft, was used to repair a facial nerve defect. The facial nerve
      of a 39-year-old woman with facial schwannoma was resected, and an island
      vascularized great auricular nerve graft from the ipsilateral side was
      transferred to bridge a 4 cm long defect of the buccal branch. Postoperatively,
      rapid nerve sprouting through the vascularized nerve graft and excellent facial
      reanimation were obtained within 6 months after surgery. This method in one-stage
      using a vascularized nerve graft is technically easy, requires a short operating
      time, has minimal donor-site morbidity, and leads to successful nerve
      regeneration postoperatively.

PMID- 15237355
TI  - Free "kite" flap: a new flap for reconstruction of small hand defects.
AB  - Small, thin, and pliable flaps are frequently required in hand surgery to
      reconstruct defects in functionally important areas such as the pulp or the
      "contact zones" of the digits. The innervated first metacarpal artery flap
      ("kite" flap) is a reliable procedure to restore sensibility in the thumb and the
      digits. Four microsurgical (free) kite flaps to the hand were performed between
      February, 1993 and August, 1999 in male patients. Follow-up examinations were
      performed in three patients. The static two-point discrimination in the kite
      flaps ranged from 8 to 15 mm and did not show any difference compared to flaps
      from the foot described in the literature. Semmes-Weinstein testing results
      ranged from normal to protective sensation with a normal sharp vs. dull
      discrimination. A free kite flap provides a valuable, safe alternative to venous
      flaps or other free flaps for reconstruction of small defects in the hand

PMID- 15237356
TI  - Big-toe replantation in a three-month-old child: case report.
AB  - A 3-month-old child underwent successful replantation of her big toe at the level
      of the metatarsophalangeal joint after traumatic amputation caused by a falling
      heavy object. The length of the big toe from the metatarsophalangeal joint to the
      tip was equal to that of the contralateral big toe at a 6-month follow-up. Within
      4 months, pain sensation returned to the toe. Traumatic amputation of the big toe
      is uncommon and only a few articles have been published on its replantation. The
      case presented here is the youngest patient for big toe replantation in the
      literature. The big toe plays an important role functionally in walking and
      standing. In addition, the appearance of the foot without the big toe may be
      unacceptable from an aesthetic point of view for many people. Reconstructive
      microsurgeons should not hesitate to replant the big toe in suitable cases, even
      if patients are only a few months old.

PMID- 15237357
TI  - An ideal and versatile material for soft-tissue coverage: experiences with most
      modifications of the anterolateral thigh flap.
AB  - Free anterolateral thigh flaps are a popular flap used for the reconstruction of
      various soft-tissue defects. From April, 2002 to June, 2003, 32 free
      anterolateral thigh flaps were used to reconstruct soft-tissue defects. Twenty
      three of these flaps were used for lower extremity reconstruction, and nine were
      used for head and neck reconstruction. There were 24 male and eight female
      patients, with ages between nine and 82 years. The size of the flaps ranged from
      11 to 32 cm in length and 6 to 18 cm in width. Five flaps required reoperation
      for vascular compromise in four patients and for twisting of the pedicle in
      another patient. While four of these were salvaged, one flap was lost due to
      recipient vessel problems. Musculocutaneous perforators were found in 23 cases,
      and septocutaneous perforators were found in nine cases. In four cases, thinning
      of the flap was performed. The flap was used as a flow-through type for lower
      extremity reconstruction in three patients. In two patients, the flap was used as
      a neurosensory type for foot reconstruction. Eighteen cases underwent split
      thickness skin grafting of the donor site and, in the remaining cases, the donor
      sites were closed primarily. In three patients, the donor areas required a
      partial skin regrafting procedure. No infections or hematomas were observed.
      Despite some variations in its vascular anatomy, the anterolateral thigh flap
      offers the following advantages: 1) it has a long and large-caliber vascular
      pedicle; 2) it has a wide, reliable skin paddle; 3) it may be harvested as a
      neurosensory flap; 4) it can be harvested whether its pedicle is septocutaneous
      or musculocutaneous; 5) it can be designed as a flow-through flap; 6) it can be
      elevated as a thin or musculocutaneous flap; and 7) the procedure can be
      performed by two teams working simultaneously, and no positional changes are
      required.

PMID- 15237359
TI  - Irrigation pressure and vessel injury during microsurgery: a qualitative study.
AB  - Irrigation solution is routinely used in microsurgery. While the anticoagulation
      solution may aid in anastomotic patency, the direct effect of pressure irrigation
      can have a detrimental effect on the vessel. An experimental study was performed
      to determine the effect of irrigation pressure on the vessel wall. Histological
      evaluation with hematoxylin and eosin (H&E) stain and scanning electron
      microscopy (SEM) was performed on the arteries of New Zealand white rabbits
      irrigated with lactated Ringer's solution at pressures of 80 mmHg, 100 mmHg, and
      500 mmHg. H&E staining and SEM microscopy demonstrated injury to the endothelial
      cells and internal elastic lamina at pressures of 100 mmHg or greater.
      Controlling microsurgical irrigation pressure to less than 100 mmHg may help to
      avoid vessel injury.

PMID- 15237358
TI  - Impact of epineurial excision of the distal recipient nerve in terminolateral
      neurorrhaphy.
AB  - Different surgical modifications were studied to improve success in
      terminolateral neurorrhaphy. The authors evaluated the efficacy of distal
      epineurial excision of the recipient nerve stump. Forty male Wistar rats were
      evaluated in four groups. The right hind limbs of the animals were used as
      experimental limbs and the left hind limbs as control limbs. The peroneal nerve
      was transected at a level 1 cm above the bifurcation of the tibial nerve. The
      proximal stump of the peroneal nerve was covered with gluteus maximus muscle
      fibers in all groups. In Group 1, the distal peroneal nerve was not processed and
      was left in the operative field. In Group 2, the distal peroneal nerve stump was
      sutured to an epineurial window on the tibial nerve by epineurial neurorrhaphy.
      In Group 3, the distal stump of the peroneal nerve was buried in the tibial nerve
      without epineurial resection, and in Group 4 with a 1-mm epineurial excision.
      Walking track analyses, electromyographic studies, and histomorphometric analyses
      were performed after a 3-month follow-up period. Statistical analysis was done
      with ANOVA and Tukey tests. No important donor-nerve injury was detected. Axonal
      regeneration and functional results were better in Group 4 compared to Groups 2
      and 3. An increased donor and recipient nerve contact surface area with the
      excision of the epineurium from the distal peroneal nerve stump (Group 4) might
      provide superior results with longer follow-up periods.

PMID- 15237360
TI  - Evaluation by scintigraphy of hindlimb ischemia in a rat model.
AB  - The subject of ischemia-reperfusion has commonly been studied in rat hindlimb
      models. Unfortunately, in these experiments, the ischemia procedures lack
      standardization. For this reason, the authors evaluated the reliability of rat
      ischemia models described in the literature using scintigraphy. The study
      comprised six groups. Each consisted of ten male Wistar rats; five of them
      underwent methoxy-isobutyl-isonitrile (MIBI) scintigraphy, which is specific for
      muscle, and the others underwent methylene diphosphanate (MDP) scintigraphy,
      which is specific for bone. In Group 1, only the iliac artery was ligated; in
      Group 2, the iliac artery and its branches, except for the superficial epigastric
      artery, were ligated; in Group 3, the iliac artery and vein were ligated; in
      Group 4, the iliac artery and all branches, including the superficial epigastric
      artery, were ligated; in Group 5, in addition to ligation of the iliac artery and
      its branches, the skin was incised circumferentially around the pelvic girdle; in
      Group 6, a tourniquet was applied to the limb at the pelvic level. After 2-hr
      warm ischemia, a radioactive tracer was injected intravenously. In the MIBI
      group, images were taken at the twentieth minute and second hour after injection,
      and in the MDP group, at the fifth minute and third hour after injection. The
      radioactivity in both hind limbs of the animal was measured, and the ratio of the
      control to the ischemic limb was calculated. In the first five groups, there was
      no necrosis in the ischemic limb at the end of 2 weeks. The measured
      radioactivity in the ischemic limb was lower than that of the control limb in all
      groups. The ratio of activity obtained from the control limb to that of the
      ischemic limb in the tourniquet group was significantly higher, compared to other
      groups in both MIBI and MDP evaluations (p < 0.005). Significant ischemia was
      also seen in the skin incision group (Group 5). A low-flow state was observed in
      the ischemic limb in Groups 1-4 using both scintigraphic modalities. The
      tourniquet method (Group 6) provided almost complete limb ischemia, compared to
      other arterial ligation methods, and it is practical to use for complete ischemia
      when studying the physiology of replantation or free flaps.

PMID- 15237363
TI  - The role of selective digestive decontamination for reducing infection in
      patients undergoing liver transplantation: a systematic review and meta-analysis.
AB  - Selective digestive decontamination (SDD) refers to the use of antimicrobials to
      reduce the burden of aerobic gram-negative bacteria and/or yeast in the
      intestinal tract to prevent infections caused by these organisms. Liver
      transplant patients are highly vulnerable to bacterial infection particularly
      with gram-negative organisms within the first month after transplantation, and
      SDD has been proposed as a potential measure to prevent these infections.
      However, the benefit of this procedure remains controversial. We undertook a
      systematic review and meta-analysis to determine whether SDD is beneficial in
      reducing infections overall and those caused by gram-negative bacteria in
      patients following liver transplantation. All studies that evaluated the efficacy
      of SDD in liver transplant patients were included. Randomized trials that
      included liver transplant patients given SDD versus either placebo or no
      treatment or minimal treatment (e.g., oral nystatin alone), and that provided
      adequate data to calculate a relative risk ratio, were included in the meta
      analysis. Our review shows that most studies found SDD to be effective in
      reducing gram-negative infection. The nonrandomized and uncontrolled trials also
      showed benefit with SDD in reducing overall infection; however, the effect on
      overall infection was limited in the 4 randomized trials, in which the pooled
      relative risk was 0.88 (95% CI, 0.7-1.1), indicating no statistically significant
      reduction in infection with the use of SDD. The summary risk ratio for the
      association between SDD and gram-negative infection was 0.16 (95% CI, 0.07-0.37),
      indicating an 84% relative risk reduction in the incidence of infection caused by
      gram-negative bacteria in patients receiving SDD in randomized trials. In
      conclusion, the available literature supports a beneficial effect of SDD on gram
      negative infection following liver transplantation; however, the risk of
      antimicrobial resistance must be considered. Larger multicenter randomized trials
      in this patient population to assess the effect of SDD in reducing infection and
      mortality, while assessing the risk of antimicrobial resistance, are needed.

PMID- 15237364
TI  - Selective decontamination of the digestive tract: rationale behind evidence-based
      use in liver transplantation.

PMID- 15237365
TI  - Disparity in use of orthotopic liver transplantation among blacks and whites.
AB  - Orthotopic liver transplantation (OLT) is the best treatment for end-stage liver
      disease. Limited data exist on the access of minorities to OLT. The aim of this
      study was to determine whether disparities exist among black and white OLT
      patients. Data were collected from the United Network for Organ Sharing on black
      and white 18-70 year-old OLT waiting list registrants (n = 29,013) and OLT
      recipients (n = 15,805) between 1994 and 1998. Standardized transplant ratios
      were generated by comparing the racial distribution of OLT patients with the US
      population. Demographic and clinical characteristics of OLT registrants were
      compared by race. Multivariate analyses were performed to identify predictors of
      time to OLT and the likelihood of dying or receiving OLT within 4 years,
      controlling for severity of illness and other factors. The standardized
      transplant ratio for black OLT recipients (0.65) was significantly lower than the
      standardized transplant ratio for white OLT recipients (1.05). Blacks were
      younger and sicker than whites. After adjustment for severity and other factors,
      time to OLT among recipients did not differ by race (P >.05). Blacks were more
      likely to die or become too ill for OLT while waiting (P <.001). Blacks were less
      likely to receive OLT within 4 years (P <.001). In conclusion, adult blacks were
      underrepresented among OLT patients. Although waiting times were similar once
      listed, black race affected outcomes while awaiting OLT. The process of referral
      and evaluation for OLT should be investigated further.

PMID- 15237366
TI  - Racial disparities in liver transplantation.

PMID- 15237368
TI  - Effects of interferon treatment on liver histology and allograft rejection in
      patients with recurrent hepatitis C following liver transplantation.
AB  - Recurrent hepatitis C after liver transplantation remains a significant cause of
      graft loss and retransplantation. Although treatment of recurrent hepatitis C
      with interferon-based regimens has become widely accepted as safe and can lead to
      sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term
      histologic improvement and the risk of precipitating graft rejection remain
      controversial. The present study is a retrospective evaluation of the clinical
      and histological consequences of treating recurrent hepatitis C with interferon
      based therapy in a selected group of liver transplant recipients. Twenty-three
      liver transplant recipients with recurrent hepatitis C and histologic evidence of
      progressive fibrosis completed at least 6 months of interferon, 83% of whom
      received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11
      patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of
      these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy
      for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA
      undetectable 24 weeks after discontinuation of interferon. Overall
      necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA
      became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94
      units before and after treatment, respectively; P =.016). However, 5 of these 11
      patients had no histologic improvement in follow-up liver histology. Liver
      biopsies in the 12 nonresponders demonstrated disease progression. Of the 23
      patients treated with interferon, 8 (35%) had evidence of acute or chronic
      rejection on posttreatment liver biopsy, most of whom had no previous history of
      rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of
      histologic rejection), and 2 experienced graft loss from chronic rejection,
      requiring retransplantation. In conclusion, interferon treatment of recurrent
      hepatitis C does not consistently improve histologic disease after virologic
      response, and it may increase the risk of allograft rejection.

PMID- 15237367
TI  - Bacteremias in liver transplant recipients: shift toward gram-negative bacteria
      as predominant pathogens.
AB  - During the 1990s, gram-positive bacteria emerged as major pathogens after liver
      transplantation. We sought to determine whether the pathogens associated with
      bacteremias in liver transplant recipients have changed. Patients included 233
      liver transplant recipients transplanted between 1989 and 2003. The proportion of
      all infections due to bacteremias increased significantly over time (P <.0001).
      Of other major infections, a trend toward a decrease in fungal infections (P
      =.089) and a significant decrease in cytomegalovirus (CMV) disease (P =.0004)
      were documented. Whereas the proportion of bacteremias due to gram-negatives
      increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram
      positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the
      period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA),
      Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent
      pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and
      Pseudomonas aeruginosa has remained unchanged (P <.20); however, that due to
      enteric gram-negative bacteria, particularly Klebsiella pneumoniae has increased
      (P =.02). Klebsiella pneumoniae isolates in the current quartile were not
      clonally related. In conclusion, bacteremias as a proportion of all infections in
      liver transplant recipients have increased significantly over time, due in part
      to a decline in infections due to other major pathogens, e.g., fungi, primarily
      Candida species, and CMV. Gram-negative bacteria have emerged as predominant
      pathogens in bacteremic liver transplant recipients.

PMID- 15237369
TI  - Outcomes of acute rejection after interferon therapy in liver transplant
      recipients.
AB  - Interferon alfa has been increasingly used against recurrent hepatitis C (HCV)
      disease in post-liver transplant (LT) recipients. A serious potential adverse
      effect is acute rejection. We reviewed our experience using interferon-based
      therapy (interferon or pegylated interferon with or without ribavirin) for
      treating recurrent HCV in LT recipients. Forty-four LT recipients were treated
      with interferon for recurrent HCV. Five of the 44 patients developed acute
      rejection during interferon-based therapy. These 5 patients started treatment of
      42.4 +/- 33.89 months (mean +/- SD) after LT. Mean (+/- SD) histological activity
      index and fibrosis scores before initiating antiviral therapy were 8.8 (+/- 1.92)
      and 2.6 (+/- 0.55), respectively. Patients were treated for 3.3 +/- 2.28 months
      (mean +/- SD) prior to rejection. At the time of rejection, HCV load was not
      detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon
      therapy, and none had stopped therapy because of adverse effects. The rejection
      was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis
      eventually developed. In the 2 patients who did not respond to rejection
      treatment, immediate graft failure occurred, leading to re-LT in 1 patient and
      death from sepsis in the other. In conclusion, the results indicate that further
      studies are needed to assess the safety of interferon in LT recipients.
      Interferon-based therapy may lead to acute rejection and subsequent graft loss
      and should therefore be used with caution. Treated recipients may also develop
      progressive cirrhosis despite achieving a sustained virological response.

PMID- 15237370
TI  - Hepatitis C, interferon, and risk of rejection after liver transplantation.

PMID- 15237371
TI  - Cyclosporine A-induced reduction of bile salt synthesis associated with increased
      plasma lipids in children after liver transplantation.
AB  - Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ
      transplantation. CsA also markedly reduces the synthesis rate of bile salts in
      rats and can inhibit biliary bile salt secretion. It is not known, however,
      whether CsA inhibits the synthesis of bile salts in humans, and whether the
      hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective
      was to assess the effects of CsA on the synthesis rate of bile salts and on
      plasma triglycerides and cholesterol levels in pediatric liver transplant
      patients. Before and after discontinuation of CsA treatment after liver
      transplantation, synthesis rate and pool size of the primary bile salts cholate
      and chenodeoxycholate were determined using a stable isotope dilution technique
      and related to plasma lipids. In 6 children (age: 3-16 years) CsA treatment was
      discontinued at 2 years (median 2.3 years) after liver transplantation.
      Discontinuation of CsA increased synthesis rate of chenodeoxycholate (+38%, P
      <.001) and cholate (+21%, P <.05) and the pool size of chenodeoxycholate (+54%, P
      <.001). Discontinuation of CsA decreased plasma levels of cholesterol (-18%, P
      <.05) and triglycerides (-23%, P <.05). Bile salt synthesis rate appeared to be
      inversely correlated with plasma cholesterol (Spearman rank correlation
      coefficient [r(s)] = -0.82, P <.01) and plasma triglyceride levels (r(s) = -0.62,
      P <.05). In conclusion, CsA inhibits bile salt synthesis and increases plasma
      concentration of cholesterol and triglycerides in pediatric liver transplant
      patients. Suppression of bile salt synthesis by long-term CsA treatment may
      contribute to hyperlipidemia and thus to increased risk for cardiovascular
      disease.

PMID- 15237372
TI  - Consumption of dietary supplements in a liver transplant population.
AB  - The extensive use of alternative medicine products, herbal remedies, and vitamins
      in large doses has reached an all time high in the general public. Some agents
      are reported and advertised as immune stimulants and may interfere with patients
      suffering from immune modification, autoimmune diseases, or transplant
      recipients. In this report, we will present an investigation into the use of
      herbal remedies and vitamins in our liver transplant population. We performed an
      investigation using a questionnaire to determine the use of herbal products and
      vitamins in our liver transplant population. Medical records were reviewed for
      each liver transplant recipient that admitted to consuming herbal products or
      vitamins. Information collected included patient demographics, transplant related
      information, laboratory tests, outcomes, and herbs or vitamin products used. A
      total of 290 patients completed and returned the questionnaire. We found 156
      admitting to taking more than a standard multivitamin and/or an herbal remedy.
      All patients were treated with steroids for allograft rejection and experienced a
      recurrence of amino transaminases following the removal of steroids. Further
      investigation into dietary supplements using a patient questionnaire form
      revealed that nearly 50% of patients admitted to using vitamins following
      transplantation, while 19% used herbal remedies combined with vitamins, most
      admitting to silymarin. One recipient was ingesting colostrum and required
      admission for the management of allograft rejection, while 5 patients had
      consumed large amounts of echinacea or CoEnzyme Q-10 and experienced elevations
      in their transaminases that resolved with discontinuation of the herb. The review
      also identified 4 patients with primary biliary cirrhosis and with transaminase
      elevation (mean values of aspartate aminotransferase and alanine aminotransferase
      levels of 88 and 95, respectively). All recipients were consuming vitamins, in
      particular high doses of vitamin E (tocopherol), more than 1 gram per day. All of
      the transplant recipients were instructed to discontinue all vitamin E products
      and the amino transaminases resolved over the following 30 to 60 days. In
      conclusion, this information reveals that a significant proportion of our liver
      transplant recipients consume herbal remedies. The results of this report suggest
      that transplant teams need to question each recipient about the use of herbal and
      vitamin remedies and educate them regarding the potential hazards.

PMID- 15237373
TI  - Survival after liver transplantation in the United States: a disease-specific
      analysis of the UNOS database.
AB  - Our goal was to describe disease-specific survival and the clinical variables
      that predict survival in a large national cohort of adult liver transplant
      recipients. Data on 17,044 adult patients who received an initial orthotopic
      liver transplant between 1990 and 1996 with follow-up through 1999 was obtained
      from the United Network for Organ Sharing (UNOS). Disease-specific Kaplan-Meier
      survival plots and Cox Proportional Hazards models were estimated, and
      differences in the clinical characteristics of patients at the time of
      transplantation by disease were examined. Overall posttransplant survival
      currently exceeds 85% in the first year and is approaching 75% at 5 years.
      Unadjusted Kaplan-Meier survival is improved for recipients who are younger,
      female, and in better clinical condition. Survival is a function of disease and
      level of illness: cancer, fulminant liver failure, alcoholic liver disease, and
      the hepatitidies have the poorest prognosis, while primary billiary cirrohsis and
      sclerosing cholangitis have the best. Recipients who were outpatients before
      transplantation have longer survival than those transplanted from the hospital or
      intensive care unit. Although the model for end-stage liver disease (MELD) score
      was designed to predict pretransplant survival, patients with higher MELD scores
      have poorer posttransplant survival, but the MELD score is less predictive than
      the specific disease. Differences in disease-specific survival are partially
      explained by differences in disease severity at the time of transplantation. In
      conclusion, Disease-specific survival models indicate that there remains
      tremendous variability in survival as a function of underlying liver disease.
      However, a significant portion of the difference in survival between diseases
      arises from differences in clinical characteristics at the time of
      transplantation.

PMID- 15237374
TI  - A comparison of disease severity and survival rates after liver transplantation
      in the United Kingdom, Canada, and the United States.
AB  - The severity of preoperative liver disease influences the outcome of liver
      transplantation, is commonly used to determine priority on liver transplant
      waiting lists, and may differ between countries with different rates of liver
      disease and organ allocation systems. We compared the relative severity of liver
      disease in transplant recipients with chronic liver disease in the United States,
      Canada, and the United Kingdom and its relation to outcome. Data were obtained
      from national databases on patients who received transplants in the year 2000.
      The data included age, gender, diagnosis, the status at the time of
      transplantation, and indices of chronic liver disease [serum bilirubin and
      international normalized ratio (INR), and serum creatinine] from which a
      comparative score [model for end-stage liver disease (MELD) score] was
      calculated. The data revealed marked differences between the three countries. No
      patient in the United Kingdom was in intensive care before transplantation
      compared with 19.3% of recipients in the United States and 7.5% in Canada. The
      median model MELD score of recipients in the United Kingdom was 10.9 compared
      with 16.1 in the United States and 17 in Canada. The median MELD score of
      transplant recipients in North America did not vary according to diagnosis,
      whereas in the United Kingdom, patients with cholestatic liver disease had a
      lower median MELD score (8.5) than those with alcoholic liver disease (15.7) at
      the time of transplantation. In conclusion, the disease severity of UK liver
      transplant recipients varied by diagnosis and was lower than recipients in North
      America; the 1-year survival rate was, however, similar between the countries.

PMID- 15237375
TI  - Pretransplant MELD score and post liver transplantation survival in the UK and
      Ireland.
AB  - It has been shown that the model for end-stage liver disease (MELD) score is an
      accurate predictor of survival in patients with liver disease without
      transplantation. Four recent studies carried out in the United States have
      demonstrated that the MELD score obtained immediately prior to transplantation is
      also associated with post-transplant patient survival. Our aim was to evaluate
      how accurately the MELD score predicts 90-day post-transplant survival in adult
      patients with chronic liver disease in the UK and Ireland. The UK and Ireland
      Liver Transplant Audit has data on all liver transplants since 1994. We studied
      survival of 3838 adult patients after first elective liver transplantation
      according to United Network for Organ Sharing categories of their MELD scores (<
      or = 10, 11-18, 19-24, 25-35, > or =36). The overall survival at 90-days was
      90.2%. The 90-day survival varied according to the United Network for Organ
      Sharing MELD categories (92.6%, 91.9%, 89.7%, 89.7%, and 70.8%, respectively; P <
      0.01). Therefore, only those patients with a MELD score of 36 or higher (3% of
      the patients) had a survival that was markedly lower than the rest. As a
      consequence, the ability of the MELD score to discriminate between patients who
      were dead or alive was poor (c-statistic 0.58). Re-estimating the coefficients in
      the MELD regression model, even allowing for nonlinear relationships, did not
      improve its discriminatory ability. In conclusion, in the UK and Ireland the MELD
      score is significantly associated with post-transplant survival, but its
      predictive ability is poor. These results are in agreement with results found in
      the United States. Therefore, the most appropriate system to support patient
      selection for transplantation will be one that combines a pretransplant survival
      model (e.g., MELD score) with a properly developed post-transplant survival
      model.

PMID- 15237376
TI  - Allocation of donor livers--is MELD enough?

PMID- 15237378
TI  - Applying expanded criteria to liver transplantation for hepatocellular carcinoma:
      too much too soon, or is now the time?

PMID- 15237377
TI  - Liver transplantation for hepatocellular carcinoma validation of present
      selection criteria in predicting outcome.
AB  - Appropriate patient selection is crucial in ensuring acceptable outcomes from
      orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The
      United Network for Organ Sharing (UNOS) has elected to prioritize HCC patients
      for OLT based on criteria of tumor burden. However, it is unclear whether these
      criteria correlate with outcome, or with the pathobiological features associated
      with tumor recurrence. Therefore, we analyzed 109 consecutive patients undergoing
      OLT for HCC at our center, to determine the utility of present selection criteria
      in predicting outcome. Pathologic tumor staging of the explanted liver was based
      on the American Tumor Study Group modified tumor node metastases (pTNM)
      classification system. Multifocality was defined as >4 tumor nodules on explant.
      Survival analysis was performed using Kaplan-Meier and Cox proportional hazards
      regression methods. At a median follow-up of 18.9 months, the overall mortality
      was 19% with 15 patients (14%) dying of recurrent HCC. Kaplan-Meier 1, 3 and 5
      year survival rates were 89.5%, 68%, and 65%, respectively. Recurrence-free rates
      of 1, 3, and 5 years were 89%, 75%, and 65%, respectively. On univariate
      analysis, the factors found to be significantly associated with recurrence of HCC
      were explant features of macrovascular invasion, tumor size (per centimeter
      increase), pTNM stage (per 1-stage increase), and pre-transplant serum
      alphafetoprotein (AFP) >300 ng/mL. In defining a threshold level, we found that
      explant tumor diameter > or =3 cm, and those tumors classified as at least pT3 on
      pathological examination, were significantly associated with recurrence (P =.01
      and.03, respectively). Tumor size on explant was found to be strongly correlated
      with multifocality (P =.017) and vascular invasion (P =.02). Patients exceeding
      pathological UNOS criteria were 3.1 times more likely to have recurrence of HCC
      (P =.03). In conclusion, we found that tumor size appears to be a surrogate
      marker for negative pathobiological predictors of outcome, i.e., vascular
      invasion and multifocality. Present UNOS selection criteria for HCC based on
      tumor burden appear to provide adequate discriminatory power in predicting
      outcome of OLT.

PMID- 15237380
TI  - Bile duct strictures after adult liver transplantation: a role for biliary
      reconstructive surgery?
AB  - There is no accurate method to determine the functional significance of bile duct
      strictures after liver transplantation, and although biliary reconstructive
      surgery (Roux-en-Y hepaticojejunostomy, HJ) is the second-line treatment in
      patients with persistent allograft dysfunction following failed endoscopic
      therapy, there is no evidence to support this approach. Liver transplant
      recipients with allograft dysfunction and demonstrable bile duct strictures who
      had undergone hepaticojejunostomy were identified from a prospective database.
      Preoperative and follow-up clinical, biochemical, and radiological data were
      collected. Perioperative liver biopsies were evaluated prospectively by two
      histopathologists blinded to clinical information. The biopsies were scored
      according to presence and severity of biliary features, fibrosis, and coexisting
      diseases. The effects of preoperative factors on postoperative allograft function
      were analyzed using SPSS statistical software. After hepatico-jejunostomy, graft
      function returned to normal in 8/44 patients (18%), improved in 16/44 (36%), but
      remained abnormal in 20/44 (45%), including 4 patients who subsequently underwent
      retransplantation. Hepaticojejunostomy was more likely to yield a favorable
      outcome (improved or normal graft function) when performed within 2 years of
      transplantation. Prolonged duration of biliary obstruction was associated with
      development of advanced graft fibrosis at the time of surgery, but neither factor
      significantly influenced postoperative graft function. In conclusion, biliary
      reconstruction successfully restores graft function in the majority of patients
      who present with anastomotic strictures within the first 2 years after liver
      transplantation. In patients presenting with bile duct strictures late after
      transplantation, surgery should be reserved for selected patients without
      histological evidence of graft fibrosis (moderate-severe) or significant
      nonbiliary pathology.

PMID- 15237379
TI  - Tacrolimus ameliorates cerebral vasodilatation and intracranial hypertension in
      the rat with portacaval anastomosis and hyperammonemia.
AB  - Arterial hyperammonemia and cerebral vasodilatation correlate with cerebral
      herniation in patients with fulminant hepatic failure (FHF). Tacrolimus is a
      calcineurin inhibitor that passes the blood-brain barrier and may increase
      cerebrovascular tone and restrict cerebral ammonia influx. In this study, we
      determined if tacrolimus prevents cerebral vasodilatation and high intracranial
      pressure (ICP) in the rat with portacaval anastomosis (PCA) challenged to high
      arterial ammonia (NH4+) concentration. Seven groups of mechanically ventilated
      rats, with 6-9 rats in each group, were investigated within 48 hours after
      construction of a PCA (4 groups) or after sham operation (3 groups). Three groups
      of the rats received infusion of NH4+ and 4 groups received saline for
      approximately 180 minutes. Two groups of the PCA rats receiving either NH4+ or
      saline had an i.v. injection of tacrolimus (0.4 mg/kg) or vehicle before start of
      NH4+ or saline infusion. Cerebral blood flow (CBF) was monitored by a laser
      Doppler probe in brain cortex. ICP was monitored by placement of a catheter in
      the cerebrospinal fluid. CBF and ICP increased in PCA rats receiving NH4+
      infusion compared to PCA controls and to all groups of sham-operated animals (P
      <.05). In the group of PCA rats pre-treated with tacrolimus before receiving
      ammonia infusion, the increase in ICP was ameliorated compared to the ammonia
      infused group receiving vehicle (P <.03). Tacrolimus also prevented an increase
      in CBF in the PCA group receiving NH4+ (P <.05) compared to the control groups.
      In conclusion, Tacrolimus prevents cerebral vasodilatation and ameliorates
      intracranial hypertension in PCA rats receiving NH4+ infusion. These findings
      indicate that tacrolimus could be of clinical value in the prevention of cerebral
      hyperemia, high ICP, and serious brain damage in patients with FHF.

PMID- 15237381
TI  - Recovery from a variegate porphyria by a liver transplantation.
AB  - The porphyrias are a group of inherited or acquired enzymatic defects of heme
      biosynthesis. Each type of porphyria has a characteristic pattern of
      overproduction and accumulation of heme precursors based on the location of
      dysfunctional enzyme in the heme synthetic pathway. Variegate porphyria, one of
      the acute hepatic porphyrias, is characterized by a partial reduction in
      protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway.
      A case of liver transplantation is described with a recovery from a variegate
      porphyria. Acute porphyria is commonly worsened by a wide variety of medications.
      We describe a step-by-step perioperative management protocol.

PMID- 15237382
TI  - Management of drug-to-drug interactions between cyclosporine A and the protease
      inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients.
AB  - Highly active antiretroviral therapy (HAART) has improved the life expectancy of
      HIV-infected patients, allowing orthotopic liver transplantation as a reasonable
      treatment option for selected patients with terminal liver disease. Both non
      nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements
      of HAART, give rise to substantial drug-to-drug interactions with
      immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12
      hour pharmacokinetic profiles in 3 HIV-positive patients after liver
      transplantation, we describe how dosing of cyclosporine A can be adjusted to
      maintain effective immunosuppressive drug levels on a daily dosing schedule when
      ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given.
      To avoid toxic drug levels, we used an orally available cyclosporine A
      formulation prepared from the commercial available intravenous solution, which
      enabled dose adjustments in 1-mg increments. Under ritonavir-boosted HAART,
      cyclosporine A levels showed markedly altered absorption/elimination
      characteristics with more or less constant blood-levels throughout the dosing
      interval and prolonged elimination half-lives up to 38 hours. To obtain
      equivalent areas under the curve of cyclosporine A, daily doses were reduced to 5
      20% of the individual standard doses given before initiation of ritonavir-boosted
      HAART. Because of the flat absorption/elimination profiles under ritonavir
      boosted HAART cyclosporine A, dosing could be reliably monitored long term by
      measuring cyclosporine A trough-levels.

PMID- 15237384
TI  - Liver transplantation with reconstruction of infrarenal vena cava and iliac
      veins.

PMID- 15237383
TI  - Sildenafil for portopulmonary hypertension in a patient undergoing liver
      transplantation.
AB  - Liver transplantation (LT) may be indicated in cirrhotic patients with underlying
      pulmonary artery hypertension. However, severe pulmonary artery hypertension with
      mean pulmonary artery pressure (mPAP) above 50 mmHg has even been considered a
      contraindication to LT. We present a cirrhotic patient with an mPAP of 56 mmHg
      measured using right heart catheterization (RHC) and with severely compromised
      physical capacity. She was first treated with sildenafil (Viagra), a potent novel
      vasodilator, and successfully transplanted later. The mPAP decreased with
      sildenafil to the level of 28-31 mmHg and her general condition improved
      markedly. An LT using piggyback technique was performed 16 weeks later. Despite 2
      reoperations for bleeding, the outcome has been excellent. In conclusion,
      treatment of severe portopulmonary hypertension (PHT) with sildenafil is
      effective. If a decrease in mPAP is achieved with sildenafil, it may improve the
      result of LT, even though no evidence of reversibility of PPHTN exists.

PMID- 15237385
TI  - Analyzing liver transplantation for fulminant hepatic failure at UCLA: a
      retrospective look at 18 years' experience.

PMID- 15237386
TI  - New total synthesis of niphatesine C and norniphatesine C based on a Sonogashira
      reaction.
AB  - The pyridine alkaloid niphatesine C and its analogue norniphatesine C were
      prepared in a short and efficient way starting from commercially available 3
      iodopyridine and undec-10-yn-1-ol using a Sonogashira reaction as the key step.
      The resulting alkylpyridines were tested for antimicrobial activity against
      several bacteria and fungi. The cytotoxic activities were determined in the MTT
      assay against HL 60 cells.

PMID- 15237387
TI  - Electrostatic surface potential calculation on several new halogenated
      benzimidazole-like dopaminergic ligands.
AB  - We examined the effects of the electron density distribution (electrostatic
      surface potential; ESP) of several new benzimidazole-type ligands on their
      binding affinity for the D(1) and D(2) dopamine receptors (DAR). Receptors were
      prepared from synaptosomal membranes of bovine caudate nuclei. [(3)H]SCH 23390
      and [(3)H]spiperone were used as specific radiolabels for the D(1) and D(2)
      receptors, respectively. The ESP of these compounds was calculated using Gaussian
      98 W software. Calculations performed with known dopaminergic ligands showed that
      the electron density charge in the aromatic ring of these compounds favors a
      higher binding affinity for the D(2) DAR. This was confirmed by the synthesis of
      halogenated analogues of several known dopaminergic ligands. Halogenation
      resulted in an increase in the positive charge of the aromatic part of the
      molecule. None of the newly synthesized compounds was efficient in displacing
      [(3)H]SCH 23390 from the D1 DAR. The introduction of chlorine into the molecule
      led to a higher binding affinity for the D(2) DAR of the new ligands in
      comparison to both parent compounds and brominated ligands. This difference
      probably originates from the difference in the sizes of chlorine and bromine
      atoms, which could influence the interaction of a ligand with the receptor
      binding site. However, among the new ligands with bromine as a substituent, two
      compounds (8b and 10b) expressed a higher binding affinity and two of them (9b
      and 11b) a lower binding affinity for the D(2) DAR, when compared to
      unsubstituted parent compounds. These results indicate that the electrostatic
      surface potential of a ligand is an important factor in its interaction with the
      D(2) DAR and that this should be taken into account during design and synthesis
      of dopaminergic compounds.

PMID- 15237388
TI  - Phenylpiperazinylmethylheterocycle derivatives: synthesis and dopamine receptor
      binding profiles.
AB  - Four series of phenylpiperazinylmethylimidazo[1, 2-a]pyridine,
      phenylpiperazinylmethylpyrrole, phenylpiperazinylmethylbenzofuran, and
      phenylpiperazinylmethylbenzothiophene derivatives were synthesized and
      investigated for their in vitro binding profiles for the dopamine receptor
      subtypes D(1), D2long, D2short, D(3) and D(4). All tested compounds showed
      selectivity towards the D(4) receptor subtype. Affinity and selectivity for D(4)
      follows the order imidazo[1, 2-a]pyridine > benzofuran > benzothiophene > pyrrole
      derivatives. The D(4)-related affinity and selectivity pattern seems to be
      dependent on the presence of a region of negative molecular electrostatic
      potential below the heterocyclic moiety.

PMID- 15237389
TI  - Synthesis and antibacterial evaluation of 1beta-methyl-2-(5-substituted
      heterocyclic carbamoyl)pyrrolidin-3-ylthio)carbapenem derivatives.
AB  - The synthesis of a new series of 1beta-methylcarbapenems having a substituted
      heterocyclic carbamoyl pyrrolidine moiety is described. Their in vitro
      antibacterial activity against both gram-positive and gram-negative bacteria was
      tested, and the effect of heterocyclic substituents on the pyrrolidine was
      investigated. One particular compound (III(d)) having a substituted oxadiazole
      moiety showed the most potent antibacterial activity.

PMID- 15237390
TI  - Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel
      nonsteroidal aromatase inhibitor.
AB  - A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying
      out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium
      hydroxide. The structure of dimer 3 has been established using various spectral
      techniques and was screened for its ability to inhibit the cytochrome P(450)
      enzyme aromatase. The dimer showed strong inhibition of human placental aromatase
      and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to
      aminoglutethimide (RP = 1, IC(50) = 18.5 microM.

PMID- 15237391
TI  - Synthesis and antimicrobial activity of new 2-[p-substituted-benzyl]-5
      [substituted-carbonylamino]benzoxazoles.
AB  - A series of 23 new 2-[p-substituted-benzyl]-5-[p-substituted-phenyl/benzyl
      carbonylamino]benzoxazole derivatives has been synthesized by reacting 5-amino-2
      [p-substituted-benzyl]benzoxazoles with the appropriate carboxylic acid
      chlorides. The structures of the synthesized compounds were confirmed by IR and
      (1)H-NMR spectral data. Antimicrobial activities of the compounds were
      investigated using the twofold serial dilution technique against two gram
      positive and two gram-negative bacteria and three Candida species in comparison
      with standard drugs. Microbiological results indicated that the newly synthesized
      2-[p-substituted-benzyl]-5-[p-substituted-phenyl/benzyl-carbonylamino]benzoxazole
      derivatives (3-25) possessed a broad spectrum of activity, showing MIC values of
      6.25-200 microg/mL against the gram-positive and gram-negative microorganisms
      tested. Moreover, they showed significant antifungal activity with MIC values of
      3.12-100 microg/mL against the Candida species tested. Especially, with a MIC
      value of 3.12 microg/mL, 2-benzyl-5-[p-bromobenzyl-carbonylamino]benzoxazole 9
      displayed the same activity against C. glabrata as the standard drug myconazol.

PMID- 15237392
TI  - Synthesis of amidinohydrazones and evaluation of their inhibitory effect towards
      aldosterone synthase (CYP11B2) and the formation of selected steroids.
AB  - The synthesis and biological evaluation of a series of amidinohydrazones (3a-h,
      6a-c, 8 and 9) as potential nonsteroidal inhibitors of aldosterone synthase
      (CYP11B2) are described. The compounds were tested in vitro using CYP11B2
      expressing fission yeast; they showed only marginal inhibitory effect. Compound
      6c was evaluated for its effect on the formation of aldosterone, cortisol,
      androstenedione, and DHEA in the adrenocortical tumor cell line NCI-H295R. It
      exhibited no significant effect on the production of these products.

PMID- 15237393
TI  - State-of-the-art of the hyphenation of capillary electrochromatography with mass
      spectrometry.
AB  - The high separation efficiency and loading capacity of capillary
      electrochromatography (CEC) make it an attractive separation mode for coupling
      with mass spectrometry (MS), which has the ability to unambiguously identify
      analytes with high selectivity and sensitivity. We present an overview of recent
      advances on both instrumentation and separation columns employed in CEC-MS
      systems. In particular, the main characteristics of the stationary phases, as
      well as the configurations of the column outlet that are related with the
      coupling arrangements of the MS ionization sources, are reported. At present,
      packed columns and conventional electrospray ionization (ESI) sources are mainly
      employed in CEC-MS. Nevertheless, the use of monolithic capillary columns and
      nanoelectrospray sources has the potential for wide acceptance in the next
      future. Moreover, the main features of several mass analyzers including ion trap,
      quadrupole, time-of-flight, magnetic sector, and Fourier transform-ion cyclotron
      resonance are examined. Finally, current applications of this technology, mainly
      in the pharmaceutical field and proteomics, are reviewed.

PMID- 15237394
TI  - Capillary electrophoresis-mass spectrometry for glycoscreening in biomedical
      research.
AB  - Application of capillary electrophoresis (CE) in combination with mass
      spectrometry (MS) and tandem MS to glycoscreening in biomedical projects is
      highlighted. In the first part recent CE-MS experiments by sheath liquid CE and
      multiple stage MS are reported. Neutral and negatively charged N-glycan mixtures
      from ribonuclease B and fetuin, high-mannose type N-glycoforms, oligosaccharides
      from lipopolysaccharides (LPS) of Haemophilus influenzae, polysaccharides of
      Pseudomonas aeruginosa and Staphylococcus aureus were analyzed. A particular
      emphasis is devoted to the applicability of novel off- and on-line CE-MS and
      tandem MS methods for screening of proteoglycan-derived oligosaccharides,
      glycosaminoglycans (GAGs), such as hyaluronates from Streptococcus agalactiae,
      chondroitin/dermatan sulfates (CS/DS) from bovine aorta and human skin fibroblast
      decorin, and heparin/heparan sulfate (HS) from porcine and bovine mucosa. The
      performance of CE-MS/MS for identification of glycoforms in glycopeptides and
      glycoproteins is illustrated by experiments performed on complex mixtures from
      urine of patients suffering from a hereditary N-acetylhexosaminidase deficiency
      (Schindler's disease) and urine of patients suffering from cancer cachexia. For
      determination of glycosylation patterns in glycoproteins like enzymes and
      antibodies by CE/MS, both CE-matrix assisted laser desorption/ionization (MALDI)
      and CE-electrospray ionization (ESI)-MS were functional. Finally, the potential
      of CE-ESI-MS strategy in glycolipid analysis is demonstrated for gangliosides
      from bovine brain for which particular CE buffer conditions are required.

PMID- 15237395
TI  - Qualitative and quantitative analysis of amino acids by capillary electrophoresis
      electrospray ionization-tandem mass spectrometry.
AB  - We describe a method to identify and quantify amino acids using capillary
      electrophoresis-electrospray ionization-triple-quadrupole tandem mass
      spectrometry (CE-ESI-MS/MS). Amino acids, including physiological amino acids,
      were first separated by CE under acidic pH conditions and then detected by MS/MS.
      To efficiently introduce the whole sample into the capillary, no electrical
      potential was applied to the electrospray probe until running electrophoresis.
      The position of the electrosprayer with respect to the MS capillary entrance
      drastically affected sensitivity and generation of cluster ions. MS/MS with
      multiple reaction monitoring (MRM) detection was performed to obtain sufficient
      selectivity and sensitivity. Under optimized CE-MS/MS conditions, the minimum
      detectable levels for 32 free amino acids normally found in proteins and other
      physiological amino acids were between 0.1 and 14 micromol/L with pressure
      injection of 50 mbar for 3 s (3 nL) at a signal-to-noise ratio of 3. For most
      amino acids, this constitutes a severalfold increase in sensitivity compared to
      CE-MS. The relative standard deviations (% RSD) for all amino acids were better
      than 0.4% for migration times and between 1.4% and 8.6% for peak areas (n = 10).
      Since amino acids exhibited characteristic MS/MS spectra, this approach is useful
      for the simultaneous, selective, quantitative, and reproducible analysis of amino
      acids in physiological and biological samples that contain various kinds of
      matrices. The power of the method was demonstrated by analyzing amino acids in
      human urine.

PMID- 15237396
TI  - Two-dimensional liquid chromatography-capillary zone electrophoresis-sheathless
      electrospray ionization-mass spectrometry: evaluation for peptide analysis and
      protein identification.
AB  - A peptide separation strategy that combines two-dimensional (2-D) liquid
      chromatography (LC)-capillary zone electrophoresis (CZE) with tandem mass
      spectrometry (MS/MS) is described for the identification of proteins in complex
      mixtures. To test the effectiveness of this strategy, a serum sample was depleted
      of the high-abundance proteins by methanol precipitation, digested with trypsin
      to generate a complex peptide mixture, and separated into 96 fractions by
      reversed-phase (RP)-LC. Compared to ion-exchange LC separations, RPLC provides
      much higher resolution and peak capacity. Fractions were collected off-line from
      the RPLC separation, and subjected to short 20 min CZE separations. The separated
      zones were introduced to the mass spectrometer through a sheathless electrospray
      ionization interface that is integrated on the separation capillary. The ease of
      fabrication of the interface and its durability allowed for the analysis of all
      fractions on a single capillary in a relatively short analysis time. A stable
      electrospray was produced at nanoliter flowrates by augmenting analyte
      electrophoretic and electroosmotic mobilities with pressure-assisted flow. Unlike
      first-dimensional ion-exchange LC fractionation, where there is a large degree of
      overlap, the CZE-MS results show less than 15% overlap between neighboring RPLC
      fractions.

PMID- 15237397
TI  - Application of capillary electrophoresis/ electrospray ionization-mass
      spectrometry to subcellular proteomics of Escherichia coli ribosomal proteins.
AB  - We introduce capillary electrophoresis-mass spectrometry (CE-MS) as an efficient
      means for the on-line separation and identification of protein mixtures. It was
      found that while CE/electrospray ionization (ESI)-MS analysis of whole-cell
      lysate was too complicated for the one-dimensional CE-MS analysis, the technique
      was useful for the analysis of protein mixtures of moderate complexity
      (approximately 50 intact proteins). CE/ESI-MS was applied to the subcellular
      proteomics of ribosomal Escherichia coli. 55 out of the 56 ribosomal proteins
      were detected with ease by using only approximately 3.4 ng of ribosomal proteins.
      In addition, it was found that the mass accuracy of the conventional MS (such as
      quadrupole ion traps) was good enough to identify many post-translational
      modifications of the intact proteins by simply comparing their measured average
      molecular weight with the average molecular weight predicted from gene banks.

PMID- 15237399
TI  - Application of capillary electrophoresis-mass spectrometry to synthetic in vitro
      glycolysis studies.
AB  - We propose an approach designed to reconstitute a metabolic pathway composed of
      multistep biochemical reactions, rather than to dissect the individual reactions
      that make up the pathway. A synthetic in vitro glycolysis was reconstructed from
      ten purified Escherichia coli (E. coli) enzymes to obtain a better understanding
      of the regulation of sequential enzymatic reactions. The key to the success of
      this approach is the ability to perform direct and simultaneous determination of
      the diverse metabolic intermediates in the pathway by capillary electrophoresis
      mass spectrometry. We observed that the pathway is regulated by a delicate
      balance between the changing metabolite concentrations and behaves like a natural
      biological oscillating network that has hitherto not been reported for E. coli
      glycolysis. The end-product, pyruvate, was periodically synthesized from glucose
      at an overall efficiency of 30%, corresponding to an average of 90% conversion
      efficiency for each of the ten steps involved. This approach is likely useful for
      the synthesis of natural products requiring complex sequential biocatalytic
      reactions.

PMID- 15237398
TI  - Platinum metallodrug-protein binding studies by capillary electrophoresis
      inductively coupled plasma-mass spectrometry: characterization of interactions
      between Pt(II) complexes and human serum albumin.
AB  - Characterizing how platinum metallocomplexes bind to human serum albumin (HSA) is
      essential in evaluating anticancer drug candidates. Using cisplatin as a
      reference complex, the application of capillary electrophoresis (CE) to reliably
      assess drug/HSA interactions was validated. Since this complex is small compared
      to the size of the protein, the binding response could only be recognized when
      applying CE coupled to a (platinum) metal-specific mode of detection, namely
      inductively coupled plasma-mass spectrometry (ICP-MS). This coupling allowed for
      confirmation of a specific affinity of cisplatin and novel Pt complexes to HSA,
      measurement of the kinetics of binding reactions, and determination of the number
      of drug molecules attached to the protein. As the cisplatin/HSA molar ratio
      increased, the reaction rate became faster with a maximum on the kinetic curve
      appearing at about 50 h of incubation at 20 times excess of cisplatin. The
      reaction was characterized as a pseudo-first order reaction with the rate
      constant k = 0.003 min(-1) at 37 degrees C. When incubated with a 20-fold excess
      of cisplatin, HSA bound up to 10 mol of Pt per mol of the protein. This is
      indicative for a strong metal-protein coordination occurring at several HSA sites
      other than the only protein cysteine residue. Structural analogs of cisplatin,
      bearing aminoalcohol ligands, showed comparable protein binding reactivity and
      stoichiometry but a common equilibrium was not reached even after one week of
      incubation. Also apparent was a two-step mechanism of the binding reaction.
      Results demonstrated the suitability of CE-ICP-MS as a rapid assay for high
      throughput studying of drug/HSA interactions.

PMID- 15237400
TI  - Analysis of high-mannose-type oligosaccharides by microliquid chromatography-mass
      spectrometry and capillary electrophoresis.
AB  - We report on microbore liquid chromatography (microLC) and capillary
      electrophoresis (CE) separation of glycopeptides and high-mannose-type
      oligosaccharides, digested from recombinant phospholipase C, expressed in Pichia
      pastoris. The glycopeptides were subject to microLC/electrospray ionization/mass
      spectrometry (ESI-MS) and microLC/ESI-tandem MS (MS/MS) analysis that revealed
      high-mannose structure size variation between Man(7)GlcNAc(2) and
      Man(14)GlcNAc(2). Then, high-performance CE was applied to identify possible
      positional isomers of the high-mannose structures. For the CE experiments, the
      oligosaccharides were released from the glycoproteins by peptide-N-glycosidase F
      and labeled with 1-aminopyrene-3,6,8-trisulfonic acid (APTS). Excellent
      separation of the possible positional isomers was attained, suggesting one for
      Man(9)GlcNAc(2), two for Man(10)GlcNAc(2), three for Man(11)GlcNAc(2),
      Man(12)GlcNAc(2), and Man(13)GlcNAc(2), and two for Man(14)GlcNAc(2). The CE
      results provided complementary information to the microLC/ESI-MS and MS/MS data
      with respect to the possible number of positional isomers.

PMID- 15237401
TI  - On-line sheathless capillary electrophoresis/nanoelectrospray ionization-tandem
      mass spectrometry for the analysis of glycosaminoglycan oligosaccharides.
AB  - A novel approach in glycosaminoglycomics, based on sheathless on-line capillary
      electrophoresis/nanoelectrospray ionization-quadrupole time of flight-mass
      spectrometry (CE/nanoESI-QTOF-MS) and tandem MS of extended chondroitin
      sulfate/dermatan (CS/DS) oligosaccharide chains is described. The methodology
      required the construction of a new sheathless CE/nanoESI-QTOF-MS configuration,
      its implementation and optimization for the high sensitivity analysis of CS/DS
      oligosaccharide mixtures from conditioned culture medium of decorin transfected
      human embryonic kidney (HEK) 293 cells. Under newly established sheathless on
      line CE/(-)nanoESI conditions for glycosaminoglycan (GAG) ionization and MS
      detection, single CS/DS oligosaccharide components of extended chain length and
      increased sulfation degree were identified. Molecular ions corresponding to
      species carrying 5 and 6 negative charges could be generated for large GAG
      oligosaccharide species in the negative ion nanoESI-MS. The optimized on-line
      conditions enabled the detection of molecular ions assigned to oversulfated
      tetradeca-, octadeca-, and eicosasaccharide CS/DS molecules, which represent the
      category of largest sulfated GAG-derived oligosaccharides evidenced by CE/ESI-MS.
      By on-line CE/ESI tandem MS in data-dependent acquisition mode the oversulfated
      eicosasaccharide species could be sequenced and the localization of the
      additional sulfate group along the chain could be determined.

PMID- 15237402
TI  - Application of capillary electrophoresis- electrospray-mass spectrometry to the
      separation and characterization of isomeric lipopolysaccharides of Neisseria
      meningitidis.
AB  - A capillary electrophoresis-electrospray-mass spectrometry technique for the
      characterization of lipopolysaccharides (LPSs) was developed, permitting the
      separation of trace-level O-deacylated LPS isoforms for subsequent structural
      characterization using tandem mass spectrometry (MS/MS). The separation buffer
      and electrospray interface were optimized first using O-deacylated LPS samples
      from large-scale preparations. It was found that with microelectrospray or sheath
      solution interface, we could separate LPS in anionic forms and detect them using
      either negative or positive ion mode MS. For negative ion detection mode MS, 30
      mM morpholine with addition of 5% v/v methanol was employed as separation buffer.
      When positive ion detection mode MS was required, 10 mM ammonium acetate with
      addition of 5% methanol was used as separation buffer. The structural assignments
      obtained from MS/MS and capillary zone electrophoresis-electrospray-MS (CZE-ESMS)
      analyses enabled the identification of isomeric glycoforms. Application of this
      technique to the analysis of LPS from the galE mutants of Neisseria meningitidis
      strain BZ157 B5+ revealed the presence of isomeric glycoforms, in which the
      location of a functional group phosphoethanolamine was found to be in either
      inner core or lipid A-OH regions. The described technique was also applied to the
      analysis of LPS samples from the galE mutant of N. meningitidis strains F1576 A4+
      and A4-. The occurrence of isomeric LPS glycoforms differing by the location or
      presence of neutral sugar residues, such as hexoses, can also be characterized
      using MS/MS.

PMID- 15237404
TI  - Development of capillary zone electrophoresis-electrospray ionization-mass
      spectrometry for the determination of lamotrigine in human plasma.
AB  - A method of coupling capillary zone electrophoresis (CZE) with electrospray
      ionization-mass spectrometry (ESI-MS) detection has been developed for monitoring
      an antiepileptic drug, lamotrigine (LTG) in human plasma. The CZE-MS was
      developed in three stages: (i) CZE separation and ESI-MS detection of LTG and
      tyramine (TRM, internal standard) were simultaneously optimized by studying the
      influence of CZE background electrolyte (BGE) pH, BGE ionic strength, and
      nebulizer pressure of the MS sprayer; (ii) sheath liquid parameters, such as pH,
      ionic strength, organic modifier content, and flow rate of the sheath liquid,
      were systematically varied under optimum CZE-MS conditions developed in the first
      stage; (iii) MS sprayer chamber parameters (drying gas temperature and drying gas
      flow rate) were varied for the best MS detection of LTG. The developed assay was
      finally applied for the determination of LTG in plasma samples. The linear range
      of LTG in plasma sample assay was between 0.1-5.0 microg/mL with a limit of
      detection as low as 0.05 microg/mL and run time less than 6 min. Finally, the
      concentration-time profile of LTG in human plasma sample was found to correlate
      well when CZE-ESI-MS was compared to a more established method of high
      performance liquid chromatography with ultraviolet detection.

PMID- 15237403
TI  - Characterization of glyco isoforms in plasma-derived human antithrombin by on
      line capillary zone electrophoresis-electrospray ionization-quadrupole ion trap
      mass spectrometry of the intact glycoproteins.
AB  - The carbohydrate structures of five isoforms of alpha-AT and two isoforms of beta
      AT were determined by applying capillary zone electrophoresis (CZE) on-line
      coupled to electrospray ionization-mass spectrometry (ESI-MS) using an ion-trap
      analyzer. For the AT preparations gained from a plasma pool at least
      semiquantitative information on the isoform-distributions could be gained. Unlike
      to the commonly used approaches starting from enzymatically treated
      glycoproteins, this approach deals with intact proteins. The high accuracy of the
      molecular mass determination obtained by the ion-trap analyzer allows one to
      calculate and ascertain the carbohydrate composition assuming no variations in
      the protein moiety of AT and to exclude or confirm the presence of the potential
      post-translational or other modifications. Therefore, the direct coupling of CZE
      with ESI-MS does not only represent a fast alternative technique to two
      dimensional electrophoresis (2-DE) but serves as a method which provides
      structural information complementary to that gained from peptide mapping methods.

PMID- 15237405
TI  - Capillary electrophoresis coupled to mass spectrometer for automated and robust
      polypeptide determination in body fluids for clinical use.
AB  - We describe the application of capillary electrophoresis (CE) coupled on-line to
      an electrospray ionization-time of flight-mass spectrometer (ESI-TOF-MS) to the
      analysis of human urine and serum for the identification of biomarkers for
      clinical diagnostics. CE-MS led to display > 1000 polypeptides present in complex
      biological samples within 45-60 min in a single analysis run. To extract the
      information of the CE-MS spectra in a timely fashion, a software was designed to
      automatically deconvolute and normalize the spectra. Both urine and serum contain
      several hundred polypeptides in samples from healthy individuals. Hence, it is
      possible to establish typical "normal urine" or "normal serum" polypeptide
      patterns. Samples from patients with different diseases display polypeptide
      patterns that differ significantly from those obtained from healthy individuals.
      Examining series of patients with the same disease allowed the establishment of
      polypeptide patterns typical for specific diseases. This permits the search for
      marker peptides specific for diseases. The data indicate that a single
      polypeptide present in all patients with the same disease, but absent in all
      healthy control individuals does not exist. The combination of several
      polypeptides found in either urine or serum or both are forming a specific
      pattern, which is indicative not only for the particular disease, but also for
      the stage of disease. CE-MS detects many polypeptides in single samples and the
      application of the software to the search of identical polypeptides excreted in
      urine allows the unbiased diagnosis based on a pattern and does not rely on
      single disease markers.

PMID- 15237406
TI  - Capillary electrophoresis-mass spectrometry of basic proteins using a new
      physically adsorbed polymer coating. Some applications in food analysis.
AB  - A new physically adsorbed capillary coating for capillary electrophoresis-mass
      spectrometry (CE-MS) of basic proteins is presented, which is easily obtained by
      flushing the capillary with a polymer aqueous solution for two min. This coating
      significantly reduces the electrostatic adsorption of a group of basic proteins
      (i.e., cytochrome c, lysozyme, and ribonuclease A) onto the capillary wall
      allowing their analysis by CE-MS. The coating protocol is compatible with
      electrospray inonization (ESI)-MS via the reproducible separation of the standard
      basic proteins (%RSD values (n = 5) < 1% for analysis time reproducibility and <
      5% for peak heights, measured from the total ion electropherograms (TIEs) within
      the same day). The LODs determined using cytochrome c with total ion current and
      extracted ion current defection were 24.5 and 2.9 fmol, respectively. Using this
      new coating lysozymes from chicken and turkey egg white could be easily
      distinguished by CE-MS, demonstrating the usefulness of this method to
      differentiate animal species. Even after sterilization at 120 degrees C for 30
      min, lysozyme could be detected, as well as in wines at concentrations much lower
      than the limit marked by the EC Commission Regulation. Adulteration of minced
      meat with 5% of egg-white could also be analysed by our CE-MS protocol.

PMID- 15237407
TI  - Highly sensitive analysis of multiple pesticides in foods combining solid-phase
      microextraction, capillary electrophoresis-mass spectrometry, and chemometrics.
AB  - A highly sensitive procedure to detect multiple pesticides at trace levels in
      foods is presented. Initially a comparative study between capillary
      electrophoresis (CE)-UV and CE-mass spectrometry (MS) is carried out analyzing
      five pesticides not studied up to now (pyrimethanil, pyrifenox, cyprodinil,
      cyromazine, and pirimicarb). The comparison between CE-UV and CE-MS is
      established in terms of separation efficiency, speed of analysis,
      reproducibility, and sensitivity. A good separation of these compounds is
      achieved by both techniques using a volatile aqueous buffer containing 0.3 M
      ammonium acetate/acetic acid at pH 4. Time analysis reproducibility is studied
      for the same day (n = 5) and three different days (n = 15), showing no
      significant differences between CE-UV and CE-MS. The study on peak areas
      reproducibility shows a slightly worse reproducibility for CE-MS compared with CE
      UV. The best limit of detection (LOD) that can be achieved for these pesticides
      using CE-UV was 0.6 microg/mL. CE-MS provides LODs one order of magnitude better
      than CE-UV. Chemometrics are used to optimize the multiple parameters that play a
      role in solid-phase microextraction (SPME) and CE-MS analysis (e.g., extraction
      and desorption times, nebulizer pressure, dry gas flow, dry gas temperature,
      percentage of organic solvent and acid in the sheath liquid, etc.). The combined
      use of chemometrics and SPME-CE-MS clearly improves the LODs that can be achieved
      allowing the detection of pesticides at concentrations down to 15 ng/mL. The
      usefulness of this approach is demonstrated detecting multiple pesticides in
      different food samples as grapes and orange juice in a single run. The
      concentrations detected are below the maximum residue limits (MRLs) permitted for
      these pesticides in foods corroborating the value of our approach. This work
      demonstrates, to our knowledge for the first time, the good possibilities of the
      combined use of SPME-CE-MS and chemometrics.

PMID- 15237408
TI  - Detection of Amadori compounds by capillary electrophoresis coupled to tandem
      mass spectrometry.
AB  - Capillary electrophoresis coupled to mass spectrometry (CE-MS) is reported for
      the first time as an alternative and powerful analytical method for the
      characterization and monitoring of N-substituted 1-amino-1-deoxyketoses (Amadori
      compounds). It allows rapid separation and identification of Amadori compounds,
      while benefiting from the well-known advantages of MS, such as specificity and
      sensitivity. Amadori compounds of several amino acids, such as glycine, valine,
      isoleucine, methionine, proline, and phenylalanine, as well as a cysteine-derived
      compound, were separated and/or discriminated using CE-MS/MS under standard
      conditions. The technique may also be useful to study the stability and
      degradation kinetics of other labile charged Maillard intermediates that play an
      important role in food and medical science.

PMID- 15237409
TI  - A beveled tip sheath liquid interface for capillary electrophoresis-electrospray
      ionization-mass spectrometry.
AB  - A simple and durable sheath liquid interface for capillary zone electrophoresis
      electrospray ionization-mass spectrometry (CZE-ESI-MS) has been developed. This
      interface utilized a beveled tip emitter and was found to be more sensitive than
      the conventional sheath liquid interface. The use of a beveled tip reduces the
      optimal flow rate and therefore decreases sample dilution. The interface utilized
      a 380 microm inner diameter and 400 microm outer diameter beveled tapered tip.
      Because of the large inner diameter and outer diameter of the tip, the interface
      is robust and can be easily implemented. The performance of this interface for
      CZE-ESI-MS and micelle electrokinetic capillary electrophoresis-electrospray-mass
      spectrometry, as demonstrated by the analysis of synthetic drugs and triazine
      mixtures, was significantly better than results obtained using a conventional
      sheath liquid interface.

PMID- 15237410
TI  - A polyamine coating for enhanced capillary electrophoresis-electrospray
      ionization-mass spectrometry of proteins and peptides.
AB  - A procedure for enhanced capillary electrophoresis-electrospray ionization-mass
      spectrometry (CE-ESI-MS) of proteins is presented. The use of a newly presented
      capillary coating, PolyE-323, provided fast separations of typically a few
      minutes with high efficiency, good deactivation, and no bleeding into the mass
      spectrometer. Capillaries coated with PolyE-323 showed high stability over a
      range of pH 2-10, and tolerance towards methanol and acetonitrile, two modifiers
      commonly used in CE-ESI-MS. Due to the speed and simplicity of the coating
      procedure, the polymeric surface could, if necessary, easily be regenerated. This
      capability is especially valuable when working with samples of complex matrix,
      where a capillary surface cleaning step might be desired in order to eliminate
      possible memory effects. The potential of PolyE-323-coated capillaries in
      bioanalysis using CE-ESI-MS was demonstrated by analyzing peptides and proteins
      up to 66 kDa using time of flight (TOF)-MS. Due to the stable, anodal
      electroosmotic flow generated by the coating, the use of a sheathless ESI
      interface was enabled, demonstrated in peptide analysis with attomole
      sensitivity. The fast on-line CE-ESI-TOF system using PolyE-323-coated
      capillaries provided efficient separation and detection of a large number of
      peaks in a short time, exemplified by the analysis of a tryptic digest of bovine
      serum albumin (BSA). The capability of the developed capillary surface coating
      was demonstrated by the separation of human plasma and cerebrospinal fluid (CSF).

PMID- 15237417
TI  - Historiography taking issue: analyzing an experiment with heroin abusers.
AB  - This article discusses the predicament of historians becoming part of the history
      they are investigating and illustrates the issue in a particular case. The case
      is that of the randomized controlled trial (RCT)-more specifically, its use for
      testing the effects of providing heroin to severe heroin abusers. I counter the
      established view of the RCT as a matter of timeless logic and argue that this
      research design was developed in the context of administrative knowledge making
      under twentieth-century economic liberalism of which it epitomizes some central
      values. I also argue that the applicability of the RCT depends on the degree to
      which its advocates can define the issue to be studied according to its inherent
      values. Next, I demonstrate how advocates of an RCT with heroin provision in the
      Netherlands steered the political discussion on heroin provision and how the
      values of economic liberalism also shaped the results of the Dutch maintenance
      experiment. In addition, I relate how my analysis of this experiment became part
      of political debates in the Netherlands. Contrary to my intentions, adversaries
      of heroin maintenance used my critique on the heroin RCT as an argument against
      heroin maintenance. Such risks are inherent to historiography and sociology of
      science aiming at practical relevance while challenging treasured scientific
      beliefs. I conclude that it still seems better to expose arguments on unjustified
      certainties than to suppress them for strategic reasons.

PMID- 15237411
TI  - A chemometric study of active parameters and their interaction effects in a
      nebulized sheath-liquid electrospray interface for capillary electrophoresis-mass
      spectrometry.
AB  - A chemometrics approach has been used for evaluating the effect of four
      experimental parameters when coupling capillary electrophoresis (CE) to
      electrospray ionization-mass spectrometry (ESI-MS). Electrospray voltage, sheath
      liquid flow rate, nebulizing gas flow rate, and spray needle position in respect
      to the MS orifice were varied according to a full factorial design. In addition
      to main effects, two interaction effects could be identified as significant when
      measuring the peak intensity of the analytes, from a sample mixture containing
      peptides and pharmaceuticals. The first interaction effects, between the
      nebulizing gas flow rate and the sheath-liquid flow rate, and the second
      interaction effect, between the nebulizing gas flow rate and the spray position,
      could further explain the impact that these variables have on the spray
      performance. The number of theoretical plates and the baseline noise were also
      measured. The sheath-liquid flow was found to significantly affect the separation
      efficiency, while the noise level mainly was controlled by the nebulizing gas
      flow. The same factorial design was also used for a CE capillary with lower
      internal diameter (ID) and the effects of the same variables were compared on
      those capillaries using equal injection volume for both capillaries. Similar
      trends were obtained in both capillaries but capillary ID was shown to be a
      significant variable when evaluating both capillaries in a single model. It was
      found that a capillary with 25 microm ID provided improved CE-MS performance over
      than corresponding 50 microm ID capillary. Enhanced sensitivity was obtained
      using the narrow-bore capillary, and at lower sheath-liquid flow rate the 25
      microm ID capillary also gave rise to more efficient peaks.

PMID- 15237418
TI  - "La manie d'ecrire": psychology, auto-observation, and case history.
AB  - This essay examines the modern psychiatric case study as a scientific method and
      as a genre of writing about the self. As psychological discourse became a
      privileged language of selfhood at the fin de siecle, the penultimate signifier
      of the self came to be found in the realm of sexuality, in the particular
      contours of an individual's sexual desire. The investigative tool used to uncover
      these secrets of identity was the case history. This article concerns an
      influential project of sexual research based on "auto-observations"
      autobiographical patient narratives-conducted by Dr. Georges Saint-Paul, who
      published under the inverted pseudonym "Laupts." The article focuses on the
      central autobiography of his collection, the "roman d'un inverti," and related
      sexological literature to suggest how this emphasis on patient stories in
      psychiatric writing engendered new narrative possibilities for doctors and
      patients alike. Putting patient stories at the center of psychiatric
      investigation created a new relationship between patient and doctor, observation
      and diagnosis, subject and discourse. The tools of psychological observation
      simultaneously placed a subject's confession more firmly at the center of the
      investigation and made it more open to interpretation by nonspecialists. Rather
      than simply confirming the authority of the trained observer, the story of
      Laupts's enquete suggests that the method actually authorized inquiry by others.

PMID- 15237419
TI  - The establishment of the department of psychiatry in the Mount Sinai Hospital: a
      conflict between neurology and psychiatry.
AB  - A conflict between neurology and psychiatry and controversies about
      psychoanalysis played an important role in the establishment of psychiatry in the
      general hospital. This article reviews the impact of this conflict on the
      establishment of an independent Department of Psychiatry in the Mount Sinai
      Hospital in New York during the first half of the twentieth century. A unique
      opportunity is provided to consider the relationships and personalities of the
      individuals involved, as well as economic, social, and scientific factors,
      including the introduction of psychoanalysis as a major psychiatric treatment.

PMID- 15237420
TI  - A biographical note on Max Friedrich (1856-1887), Wundt's first PhD student in
      experimental psychology.
AB  - This article unveils some previously unknown facts about the short life of Max
      Friedrich (1856-1887), the author in 1881 of the first PhD dissertation on
      experimental psychology, written under the supervision of Wilhelm Wundt: "On the
      Duration of Apperception for Simple and Complex Visual Stimuli." The article
      describes Friedrich's family background and life, professional career as a
      teacher, and works in psychology and mathematics.

PMID- 15237424
TI  - Preparation of magnetic polybutylcyanoacrylate nanospheres encapsulated with
      aclacinomycin A and its effect on gastric tumor.
AB  - AIM: To evaluate the effect of aclacinomycin A-loaded magnetic
      polybutylcyanoacrylate nanoparticles on gastric tumor growth in vivo and in
      vitro. METHODS: Magnetic polybutylcyanoacrylate (PBCA) nanospheres encapsulated
      with aclacinomycin A (MPNS-ACM) were prepared by interfacial polymerization.
      Particle size, shape and drug content were examined. Female BABL/c nude mice were
      implanted with MKN-45 gastric carcinoma tissues subcutaneously to establish human
      gastric carcinoma model. The mice were randomly divided into 5 groups of 6 each:
      ACM group (8 mg/kg bm); group of high dosage of MPNS-ACM (8 mg/kg bm); group of
      low dosage of MPNS-ACM (1.6 mg/kg bm); group of magnetic PBCA nanosphere (MPNS)
      and control group (normal saline). Magnets (2.5 T) were implanted into the tumor
      masses in all of the mice one day before the therapy. Above-mentioned drugs were
      administered intravenously to the mice of every group on the first day and sixth
      day. When the mice were sacrificed, tumor weight was measured, and the assay of
      granulocyte- macrophage colony forming-unit (CFU-GM) was performed on semi-solid
      culture. White blood cell, alanine aminotransferase and creatine were examined. 3
      (4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to
      examine the viability of MKN-45 cells after incubation with different
      concentrations of ACM, MPNS and MPNS-ACM suspension respectively for 48 h.
      RESULTS: Content of ACM in MPNS-ACM was 12.0% and the average diameter of the
      particles was 210 nm. The inhibitory rates of ACM (8 mg/kg bm), high dosage of
      MPNS-ACM (8 mg/kg bm), low dosage of MPNS-ACM (1.6 mg/kg bm) and MPNS on human
      gastric carcinoma in nude mice were 22.63%, 52.55%, 30.66% and 10.22%,
      respectively. There was a significant decrease in the number of CFU-GM of bone
      marrow in ACM group compared with control group, whereas no obvious change was
      observed in that of the nanosphere groups. The values of 50% inhibition
      concentration (IC50) of ACM, MPNS and MPNS-ACM were 0.09, 97.78 and 1.07
      microg/mL, respectively. CONCLUSION: The tumor inhibitory rate of MPNS-ACM was
      much higher than that of ACM under magnetic field and the inhibition on bone
      marrow was alleviated significantly compared with ACM group.

PMID- 15237423
TI  - L-arginine-induced experimental pancreatitis.
AB  - Despite medical treatment, the lethality of severe acute pancreatitis is still
      high (20-30%). Therefore, it is very important to find good animal models to
      characterise the events of this severe disease. In 1984, Mizunuma et al.
      developed a new type of experimental necrotizing pancreatitis by intraperitoneal
      administration of a high dose of L-arginine in rats. This non-invasive model is
      highly reproducible and produces selective, dose-dependent acinar cell necrosis.
      Not only is this a good model to study the pathomechanisms of acute necrotizing
      pancreatitis, but it is also excellent to observe and influence the time course
      changes of the disease. By writing this review we illuminate some new aspects of
      cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately,
      the reviews about acute experimental pancreatitis usually did not discuss this
      model. Therefore, the aim of this manuscript was to summarise the observations
      and address some challenges for the future in L-arginine-induced pancreatitis.

PMID- 15237425
TI  - Clinical significance of serum vascular cell adhesion molecule-1 levels in
      patients with hepatocellular carcinoma.
AB  - AIM: To evaluate the correlation between serum vascular cellular adhesion
      molecule-1 (VCAM-1) levels and clinicopathological features in patients with
      hepatocellular carcinoma (HCC). METHODS: Ninety-six patients who underwent HCC
      resection were recruited in the study. Preoperative serum levels of soluble VCAM
      1 were measured by enzyme-linked immunosorbent assay. RESULTS: Serum VCAM-1 level
      in HCC patients was inversely correlated with platelet count (r=-0.431, P<0.001)
      and serum albumin level (r=-0.279, P<0.001), and positively correlated with serum
      bilirubin level (r=0.379, P<0.001). Serum VCAM-1 level was not associated with
      tumor characteristics such as tumor size, venous invasion, presence of
      microsatellite nodules, tumor grade and tumor stage. Serum VCAM-1 level was
      significantly higher in HCC patients with cirrhosis compared with those without
      cirrhosis (median 704 vs 546 ng/mL, P<0.001). Furthermore, a significantly better
      disease-free survival was observed in HCC patients with low VCAM-1 level
      (P=0.019). CONCLUSION: Serum VCAM-1 level appears to reflect the severity of
      underlying chronic liver disease rather than the tumor status in HCC patients,
      and low preoperative serum VCAM-1 level is predictive of better disease-free
      survival after surgery.

PMID- 15237426
TI  - Effects of KAI1 gene on growth and invasion of human hepatocellular carcinoma
      MHCC97-H cells.
AB  - AIM: To study the effects of sense and antisense KAI1 genes on the growth and
      invasion of human hepatocellular carcinoma (HCC) cell line MHCC97-H. METHODS:
      KAI1 sense and antisense eukaryotic expression plasmids were constructed using
      subclone technique and transfected into MHCC97-H cells respectively by DOTAP
      liposome. After successful transfection was confirmed, in vitro growth curve,
      cell cycles, plate clone formation efficiency, invasive ability in Boyden Chamber
      assay and ultrastructural morphology were studied. RESULTS: KAI1 sense and
      antisense genes had no significant effects on the cell growth curve and cell
      cycles. After transfection with sense KAI1 gene, decreased invasive ability in
      Boyden Chamber assay and decreased amount of mitochondria, but no significant
      changes of plate clone formation efficiency were observed in MHCC97-H-S cells.
      The plate clone formation efficiency and invasive ability in Boyden Chamber assay
      were significantly increased in MHCC97-H-AS cells, after transfection with
      antisense KAI1 gene. Furthermore, increased amount of mitochondria, rough
      endoplasmic reticulum, Golgi apparatus and expanded endoplasmic reticulum were
      also noted in MHCC97-H-AS cells. CONCLUSION: Changes of KAI1 expression in HCC
      cells may alter their invasive and metastasis ability of the tumor.

PMID- 15237427
TI  - Growth inhibition and apoptosis induction of tanshinone II-A on human
      hepatocellular carcinoma cells.
AB  - AIM: To evaluate the effects of tanshinone II-A on inducing growth inhibition and
      apoptosis of human hepatocellular carcinoma (HCC) cells. METHODS: The human
      hepatocellular carcinoma cell line SMMC-7721 was used for the study. The cells
      were treated with tanshinone II-A at different doses and different times. Cell
      growth and proliferation were measured by MTT assay, cell count and colony
      forming assay. Apoptosis induction was detected by microscopy, DNA ladder
      electrophoresis and flow cytometry. RESULTS: In MTT assay, the inhibitory effect
      became gradually stronger with the passage of time, 24, 48, 72 and 96 h after
      treatment with tanshinone II-A, and the most significant effect was observed at
      72 h. On the other hand, the increase of doses (0.125, 0.25, 0.5, 1.0 mg/L
      tanshinone II-A) resulted in enhanced inhibitory effect. The growth and
      proliferation of SMMC-7721 cells were obviously suppressed in a dose- and time
      dependent manner. The results of cell count were similar to that of MTT assay. In
      colony-forming assay, the colony-forming rates were obviously inhibited by
      tanshinone II-A. In tanshinone II-A group, the morphology of cellular growth
      inhibition and characteristics of apoptosis such as chromatin condensation,
      crescent formation, margination and apoptotic body were observed under light and
      transmission electron microscopes. DNA ladder of cells was presented in
      electrophoresis. The apoptosis index (AI) was 16.9% (the control group was 4.6%)
      in flow cytometry. The cells were arrested in G(0)/G(1) phase, and the
      expressions of apoptosis-related genes bcl-2 and c-myc were down-regulated and
      fas, bax, p53 up-regulated. CONCLUSION: Tanshinone II-A could inhibit the growth
      and proliferation of HCC cell effectively in vitro by apoptosis induction, which
      was associated with up-regulation of fas, p53, bax, expression and down
      regulation of bcl-2 and c-myc.

PMID- 15237428
TI  - Prokaryotic expression and renaturation of engineering chimeric Fab antibody
      against human hepatoma.
AB  - AIM: To express chimeric Fd (cFd) and chimeric light chain (cL) in E.coli
      respectively and refold them into chimeric Fab (cFab) antibody. METHODS: cFd and
      cL genes were respectively inserted into the prokaryotic expression vector pET32a
      to construct recombinant vectors pET32a/cFd and pET32a/cL. Then, the competent
      E.coli cells were transformed by the recombinant vectors and induced by IPTG.
      Moreover, a large quantity of cFd and cL expression products were prepared and
      mixed with equal molar to refold into cFab by gradient dialysis. The refolded
      products were identified and analyzed by sodium SDS-PAGE, Western blotting, ELISA
      and HPLC. RESULTS: High efficient prokaryotic expressions of both cFd and cL in
      the form of non-fusion protein were obtained with the expression levels of 28.3%
      and 32.3% of total bacteria proteins, respectively. Their relative molecular
      masses were all 24 ku or so, and both of them mainly existed in the form of
      inclusion bodies. In addition, cFd and cL were successfully refolded into cFab by
      gradient dialysis, with about 59.45% of recovery when the starting total protein
      concentration was 100 microg/mL. The renatured cFab could specifically bind to
      related antigen with high affinity. CONCLUSION: The cFab antibody against human
      hepatoma was highly and efficiently expressed and refolded, which laid a solid
      foundation for studying its application in the treatment of hepatoma.

PMID- 15237429
TI  - Expression of cancer-testis antigens in hepatocellular carcinoma.
AB  - AIM: To investigate the expression of cancer-testis (CT) antigens MAGE-1, SSX
      1,CTp11 and HCA587 genes in hepatocellular carcinoma (HCC) and the possibility of
      applying these antigens as targets for specific immunotherapy for HCC. METHODS:
      Expression levels of MAGE-1, SSX-1, CTp11 and HCA587 mRNA were detected with
      reverse transcription polymerase chain reaction (RT-PCR) in HCC tissues and
      corresponding adjacent non-cancerous tissues from 105 HCC patients, 40 samples of
      cirrhosis and normal liver tissues. Genes of five samples with positive PCR
      results were sequenced. RESULTS: Of 105 HCC tissues, MAGE1, SSX-1,CTp11 and
      HCA587 mRNA expressions were detectable in 75.2%(79/105), 72.4%(76/105),
      62.9%(66/105) and 56.2%(59/105) of HCC samples, respectively. About
      93.3%(98/105), 72.4%(76/105), 48.6%(51/105) and 37.1%(39/105) of HCC tissues
      positively expressed at least one, two, three, and four members of CT antigens,
      respectively. Conversely, only SSX-1 could be detectable in 2.9%(3/105) of the
      corresponding adjacent non-HCC tissues in which no metastatic lesion was found.
      Of the latter 3 patients, biopsy samples far from tumor were obtained in 2
      patients and RT-PCR indicated no expression of SSX-1 mRNA in these two samples.
      In addition, none of 40 samples of cirrhotic and normal liver tissues expressed
      CT antigen gene mRNA. DNA sequences confirmed that the RT-PCR products were true
      target cDNA. No relationship was found between expression of CT antigens and
      clinico pathological indicators such as age, gender, tumor size, degree of tumor
      differentiation, serum alpha-fetoprotein level and infection of hepatitis B virus
      or hepatitis C virus (P>0.05). CONCLUSION: CT antigens genes (MAGE-1, SSX-1,
      CTp11 and HCA587) are expressed with high percentage and specificity in HCC and
      their products are promising targets for antigen-specific immunotherapy of HCC.
      High frequent co-expression of multiple members of CT antigens in HCC provides
      possibility of polyvalent vaccinations for HCC.

PMID- 15237430
TI  - A DNA vaccine against extracellular domains 1-3 of flk-1 and its immune
      preventive and therapeutic effects against H22 tumor cell in vivo.
AB  - AIM: To construct a DNA vaccine against extracellular domains 1-3 of fetal liver
      kinase-1 (flk-1), and to investigate its preventive and therapeutic effect
      against H22 cell in vivo. METHODS: Flk-1 DNA vaccine was produced by cloning
      extracellular domains 1-3 of flk-1 and by inserting the cloned gene into pcDNA3.1
      (+). Fifteen mice were divided into 3 groups and inoculated by vaccine, plasmid
      and saline respectively to detect specific T lymphocyte response. Thirty Mice
      were equally divided into preventive group and therapeutic group. Preventive
      group was further divided into V, P, and S subgroups, namely immunized by
      vaccine, pcDNA3.1 (+) and saline, respectively, and attacked by H22 cell.
      Therapeutical group was divided into 3 subgroups of V, P and S, and attacked by
      H22, then treated with vaccine, pcDNA3.1 (+) and saline, respectively. The tumor
      size, tumor weight, mice survival time and tumor latency period were compared
      within these groups. Furthermore, intratumoral microvessel density (MVD) was
      assessed by immunohistochemistry. RESULTS: DNA vaccine pcDNA3.1 (+) flk-1-domains
      1-3 was successfully constructed and could raise specific CTL activity. In the
      preventive group and therapeutic group, tumor latency period and survival time
      were significantly longer in vaccine subgroup than that in P and S subgroups
      (P<0.05); the tumor size, weight and MVD were significantly less in vaccine
      subgroup than that in P and S subgroups (P<0.05). The survival time of
      therapeutic vaccine subgroup was significantly shorter than that of preventive
      vaccine subgroup (P<0.05); the tumor size, and MVD of therapeutic vaccine
      subgroup were significantly greater than that of preventive vaccine subgroup
      (P<0.05). CONCLUSION: DNA vaccine against flk-1 domains 1-3 can stimulate potent
      specific CTL activity; and has distinctive prophylactic effect on tumor H22; and
      also can inhibit the tumor growth in vivo. This vaccine may be used as an
      adjuvant therapy because it is less effective on detectable tumor.

PMID- 15237431
TI  - Identification of 5' capped structure and 3' terminal sequence of hepatitis E
      virus isolated from Morocco.
AB  - AIM: To examine 5' and 3' terminal sequences of hepatitis E virus (HEV) isolated
      from Morocco, to confirm 5' methylated cap structure of the genome, and to
      investigate whether the 3' UTR can be used to distinguish HEV genotypes instead
      of HEV complete genome sequence. METHODS: RNA ligase-mediated rapid amplification
      of cDNA ends (RLM-RACE) was employed to obtain the 5' and 3' terminal sequences
      of HEV Morocco strain. The 3' UTR sequence of the Morocco strain was compared
      with that of the other 29 HEV strains using the DNAStar software. RESULTS: The 5'
      PCR product was obtained only from the RLM-RACE based on the capped RNA template.
      The 5' UTR of the Morocco strain had 26 nucleotides, and the 3' UTR had 65
      nucleotides upstream to the polyA. The 5' UTR between HEV strains had only point
      mutations of nucleotides. The phylogenetic tree based on the sequences of 3' UTR
      was not the same as that based on the complete sequences. CONCLUSION: The genome
      of HEV Morocco strain was methylated cap structure. The 3' terminal sequence can
      not be used for distinguishing HEV genotype for all HEV strains in place of the
      whole HEV genome sequence.

PMID- 15237432
TI  - Inhibition of human La protein by RNA interference downregulates hepatitis B
      virus mRNA in 2.2.15 cells.
AB  - AIM: To investigate the role of human La protein in HBV mRNA expression. METHODS:
      Three human La protein (hLa) specific siRNA expression cassettes (SECs)
      containing U6+1 promoter were prepared via one-step overlapping extension PCR.
      After transfection with SECs into HepG2 cells, inhibition effects on hLa
      expression were analyzed by semi-quantitative RT-PCR and Western blotting. Then,
      effective SECs were screened out and transfected into 2.2.15 cells, a stable HBV
      producing cell line. HBV surface antigen (HBsAg) and e antigen (HBeAg) secretions
      into culture media were detected by microparticle enzyme immunoassay (MEIA) and
      HBs and HBe mRNA levels were analyzed by semi-quantitative RT-PCR. RESULTS: SEC
      products containing U6+1 snRNA promoter, and 3 sites of hLa mRNA specific siRNA
      were obtained successfully by one-step overlapping extension PCR and could be
      directly transfected into HepG2 cells, resulting in inhibition of La protein
      expression in both mRNA and protein levels, among which U6+1-hLa833 was the most
      efficient, which reduced 18.6-fold mRNA and 89% protein level respectively. In
      2.2.15 cells, U6+1-hLa833 was also efficient on inhibition of hLa expression.
      Furthermore, semi-quantitative RT-PCR showed that HBs and HBe mRNA levels were
      significantly decreased by 8- and 66-fold in U6+1-hLa833 transfected cells
      compared to control. Accordingly, HBsAg and HBeAg secretions were decreased
      partly posttransfection with SECs. CONCLUSION: PCR-based SECs can be used to
      mediate RNAi in mammalian cells and provide a novel approach to study the
      function of La protein. The inhibition of La protein expression can result in a
      significant decrease of HBV mRNA, which implies that the hLa protein is also
      involved HBV RNA metabolism as one of the HBV RNA-stabilizing factors in human
      cells.

PMID- 15237433
TI  - Helicobacter pylori lipopolysaccharide: biological activities in vitro and in
      vivo, pathological correlation to human chronic gastritis and peptic ulcer.
AB  - AIM: To determine the biological activity of Helicobacter pylori (H. pylori)
      lipopolysaccharide (H-LPS) and understand pathological correlation between H-LPS
      and human chronic gastritis and peptic ulcer. METHODS: H-LPS of a clinical H.
      pylori strain and LPS of Escherichia coli strain O55:B5 (E-LPS) were extracted by
      phenol-water method. Biological activities of H-LPS and E-LPS were detected by
      limulus lysate assay, pyrogen assay, blood pressure test and PBMC induction test
      in rabbits, cytotoxicity test in NIH 3T3 fibroblast cells and lethality test in
      NIH mice. By using self-prepared rabbit anti-H-LPS serum as the first antibody
      and commercial HRP-labeled sheep anti-rabbit sera as the second antibody, H-LPS
      in biopsy specimens from 126 patients with chronic gastritis (68 cases) or
      gastric ulcer (58 cases) were examined by immunohistochemistry. RESULTS:
      Fibroblast cytotoxicity and mouse lethality of H-LPS were weaker than those of E
      LPS. But the ability of coagulating limulus lysate of the two LPSs was similar
      (+/0.5 ng/mL). At 0.5 h after H-LPS injection, the blood pressures of the 3
      rabbits rapidly declined. At 1.0 h after H-LPS injection, the blood pressures in
      2 of the 3 rabbits fell to zero causing death of the 2 animals. For the other one
      rabbit in the same group, its blood pressure gradually elevated. At 0.5 h after E
      LPS injection, the blood pressures of the three rabbits also quickly declined and
      then maintained at low level for approximately 1.0 h. At 0.5 h after injection
      with H-LPS or E-LPS, PBMC numbers of the rabbits showed a remarkable increase.
      The total positivity rate of H-LPS from 126 biopsy specimens was 60.3%(76/126). H
      LPS positivity rate in the biopsy specimens from chronic gastritis (50/68, 73.5%)
      was significantly higher than that from gastric ulcer (26/58, 44.8%)
      (chi(2)=10.77, P<0.01). H-LPS positivity rates in biopsy specimens from chronic
      superficial gastritis (38/48, 79.2%) and chronic active gastritis (9/10, 90.0%)
      were significantly higher than that of the patients with atrophic gastritis
      (3/10, 30.0%) (chi(2)=7.50-9.66, P<0.01). CONCLUSION: The biological activities
      of H-LPS were weaker than those of E-LPS, the activities of H-LPS of lowering
      rabbit blood pressure and inducing rabbit PBMC were relatively stronger. H-LPS
      may play a critical role in inducing inflammatory reaction in human gastritis.

PMID- 15237434
TI  - Gene distribution of cagII in Helicobacter pylori-infected patients of Zhejiang
      Province.
AB  - AIM: To determine the prevalence of genotypes of cagII in Helicobacter pylori (H
      pylori)-infected patients in Zhejiang Province and investigate the relationship
      between these genotypes and the types of gastroduodenal diseases. METHODS: One
      hundred and seventy one clinical isolates were collected from 70 chronic
      superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21
      duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma
      patients. Polymerase chain reaction assays were performed for analysis of cagT,
      ORF13 and ORF10 genes in the cagII region. RESULTS: Of 171 H pylori isolates from
      Zhejiang patients, 159(93.0%) were positive for all the three loci. One isolate
      (0.6%) was negative for all the three loci, and 11(6.4%) were partially deleted
      in cagII. The positive rates of cagT, ORF13 and ORF10 genes were 97.1%, 94.7% and
      99.4%, respectively. In the strains isolated from the patients with diseases
      including chronic superficial gastritis, chronic atrophic gastritis, gastric
      ulcer and duodenal ulcer, the sitive rates of cagT were 95.7%, 100.0%, 95.1% and
      100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and
      100.0%, respectively. The sitive rates of ORF10 were 98.6%, 100.0%, 100.0% and
      100.0%, respectively. The three genes were all positive in the three H pylori
      strains isolated from the patients with both gastric and duodenal ulcer. In the
      five strains isolated from the patients with gastric adenocarcinoma, only one
      isolate was negative for ORF13. There were no significant differences of the
      cagT, ORF13 and ORF10 genes among the different gastroduodenal diseases including
      chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer,
      duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma
      (chi(2)=3.098, P>0.05 for cagT; chi(2)=3.935, P>0.05 for ORF13 and chi(2)=6.328,
      P>0.05 for ORF10). CONCLUSION: The cagII is not a uniform and conserved entity.
      Although the genes in cagII are highly associated with the gastroduodenal
      diseases, the clinical outcome of H pylori infection is not reliably predicted by
      the three genes in cagII in patients from Zhejiang Province.

PMID- 15237435
TI  - Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to
      Lewis b antigen.
AB  - AIM: To evaluate the effects of animal milk containing fucosylated antigens on
      Helicobacter pylori (H. pylori) binding to Lewis b antigen. METHODS: A mammary
      gland expression vector containing human alpha1-3/4-fucosyltransferase cDNA
      sequences was constructed. Transient expression of human alpha1-3/4
      fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice
      were performed. The adhesion inhibitory properties of milk samples were analyzed
      by using H. pylori. RESULTS: Goat milk samples were found to inhibit bacterial
      binding to Lewis b antigen. The highest inhibition was observed 42 h after
      injection of the plasmid. The binding activity of H. pylori to Lewis b antigen
      reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit
      H. pylori binding to Lewis b antigen. CONCLUSION: The use of "humanized" animal
      milk produced by the transgenic introduction of fucosylated antigen can perhaps
      provide an alternative therapy and preventive measure for H. pylori infection.

PMID- 15237436
TI  - Microencapsulated hepatocytes and islets as in vivo bioartificial liver support
      system.
AB  - AIM: To confirm the xenotransplantation of microencapsulated hepatocytes and
      islets as a temporary bioartificial liver support system for mice with acute
      liver failure (ALF). METHODS: Mice were rendered ALF by a single intra-peritoneal
      injection of D-galactosamine (D-gal) and their tail blood was sampled to examine
      differences in blood ALT, albumin (ALB), total bilirubin (TB) and glucose (GLU)
      between 4 experimental groups. Rat hepatocytes and islets were collected and
      microencapsulated referring to both Sun's and Fritschy's methods. Mice were
      grouped into control group (CG), free hepatocyte group (FHG), microencapsulated
      hepatocyte group (MHG) and microencapsulated hepatocyte plus islet group (HIG).
      Tissue samples were subjected to microscopic and electron microscopic (EM)
      examinations. RESULTS: The highest survival was observed in HIG, surprisingly at
      100%(16/16), while the lowest was in CG at 12.5%(2/16), with inter-group
      statistical difference P<0.05. ALT levels revealed no statistical difference
      between groups but the ALB level of HIG descended by the slightest margin
      (q=(0.54, 0.24, 1.33), P<0.05) at the time when it reached the lowest point in
      all groups. TB of HIG returned to normal reference range (NRR) statistically
      sooner than that of others after a fierce elevation. No statistical inter-group
      difference was observed in GLU levels. Fusion between hepatocytes and beta cells
      was demonstrated giving rise to theoretical assumptions. CONCLUSION: Hepatocytes
      to be microencapsulated together with islets should be a preferred in vivo
      hepatic functional supporting system, which can dramatically prolong survival and
      improve living status.

PMID- 15237437
TI  - Contribution of C3d-P28 repeats to enhancement of immune responses against HBV
      preS2/S induced by gene immunization.
AB  - AIM: To investigate whether P28 derived from C3d can enhance the immune response
      to HBV-preS2/S induced by directly injection of naked plasmids containing
      variable repeats of P28 and HBV-preS2/S in fusion form. METHODS: One to four
      copies of C3d-P28 coding gene, amplified by PCR and modified by restriction
      endonucleases digestion, were subcloned into a eukaryotic expression vector
      pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4
      (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the
      pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were
      primed by intramuscular gene immunization with 100 microg different recombinant
      plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein
      (1 microg) 12 wk post-priming. The levels and avidity of specific IgG in sera
      collected at the indicated times from each group were determined by ELISA and
      NaSCN-displacement ELISA, respectively. RESULTS: HBsAg specific antibody response
      was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4] and pVAON33
      S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S
      P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest
      level of the specific antibody response was observed in the groups primed with
      pVAON33-S2/S-P28.4 (P<0.01). After secondary immunization with specific antigen,
      the acceleration of antibody levels was significantly higher and faster in the
      mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing
      preS2/S only (P<0.05). Interestingly, mice primed with DNA expressing preS2/S
      P28.4 fusions maintained the highest levels of anti-HBs antibodies in all
      animals. The avidity assay showed that the avidity index (AI) collected at 18 wk
      from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were
      significantly higher than that from preS2/S-DNA vaccinated mice (P<0.01).
      CONCLUSION: Different repeats of C3d-P28 can enhance both humoral immune response
      and avidity maturation of specific antibodies induced by gene immunization, in
      which four copies of C3d-P28 may be necessary to achieve the most modest antibody
      response.

PMID- 15237438
TI  - Expression and in vitro cleavage activity of anti-caspase-7 hammerhead ribozymes.
AB  - AIM: To prepare hammerhead ribozymes against mouse caspase-7 and identify their
      cleavage activity in vitro, in order to select a ribozyme with specific cleavage
      activity against mouse caspase-7 as a potential gene therapy for apoptosis
      related diseases. METHODS: Anti-caspase-7 ribozymes targeting sites 333 and 394
      (named Rz333 and Rz394) were designed by computer software, and their DNA
      sequences encoding ribozymes were synthesized. Caspase-7 DNA sequence was
      acquired by RT-PCR. Ribozymes and caspase-7 DNA obtained by in vitro
      transcription were cloned into pBSKneo U6' and pGEM-T vectors, respectively. The
      cleavage activity of ribozymes against mouse caspase-7 was identified by cleavage
      experiments in vitro. RESULTS: Rz333 and Rz394 were designed and their DNA
      sequences were synthesized respectively. The expression vector of caspase-7 and
      plasmids containing Rz333 and Rz394 were reconstructed successfully. Ribozymes
      and caspase-7 mRNA were expressed by in vitro transcription. In vitro cleavage
      experiment showed that 243-nt and 744-nt segments were produced after caspase-7
      mRNA was mixed with Rz333 in equivalent, and the cleavage efficiency was 67.98%.
      No cleaved segment was observed when caspase-7 mRNA was mixed with Rz394.
      CONCLUSION: Rz333 can site-specific cleave mouse caspase-7 mRNA, and it shows a
      potential for gene therapy of apoptosis-related diseases by down-regulating gene
      expression of caspase-7.

PMID- 15237439
TI  - Effects of octreotide on acute necrotizing pancreatitis in rabbits.
AB  - AIM: To assess the role of oxygen-derived free radicals and cytokines in the
      pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the
      preventive effects of octreotide towards the development of acute pancreatitis.
      METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by
      retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in
      the pancreatic duct. Sham-operated animals served as control. Octreotide 1
      mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis.
      Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after
      pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and
      levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase
      (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic
      tissue were measured. RESULTS: Serum TNF-alpha and IL-6 levels increased
      significantly 3 h after the onset of pancreatitis, and then returned to control
      level. The tissue concentration of MDA was significantly elevated at 24 h, while
      the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all
      significantly decreased in animals with pancreatitis as compared to the control.
      Octreotide pretreatment significantly reversed the changes in cytokines and
      reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase
      activity and did not have any beneficial effects on the development of
      histopathological changes. CONCLUSION: Oxygen-derived free radicals and
      proinflammatory cytokines are generated at an early stage of NaTc-induced acute
      pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of
      cytokines and generation of reactive oxygen metabolites, but does not have any
      beneficial effects on the development of necrotizing pancreatitis.

PMID- 15237440
TI  - Changes of gut flora and endotoxin in rats with D-galactosamine-induced acute
      liver failure.
AB  - AIM: To investigate the changes of gut microflora and endotoxin levels in rats
      with acute liver failure (ALF) induced by D-galactosamine (GalN). METHODS: Flora
      and endotoxin levels in the jejunum, ileum and colon in normal rats (group A) and
      rats with GalN -induced ALF were determined at 24 h (group B) or 48 h (group C)
      after GalN injection, as well as the endotoxin level in portal venous blood (PVB)
      and right ventricle blood (RVB) were determined by chromogenic limulus amoebocyte
      assay. RESULTS: Intestinal (jejunum, ileum, colon) lactobacillus count was
      statistically reduced in group B compared with those in group A (3.4+/-0.3 vs
      4.9+/-0.3, 6.1+/-0.4 vs 8.0+/-0.3, 8.1+/-0.2 vs 9.3+/-0.2, P<0.001, P<0.001 and
      P<0.001 respectively) and recovered partially in the group C compared with those
      in the group B, whereas the count of Enterobacteriaceae in the jejunum, ileum and
      colon in group B was increased markedly compared with those in the group A (5.1+/
      0.3 vs 3.6+/-0.2, 6.9+/-0.5 vs 5.3+/-0.3, 8.7+/-0.2 vs 7.6+/-0.1, P<0.001, P<0.05
      and P<0.05 respectively) and restored partially in the group C compared with
      those in the group B. The endotoxin level in ileum was increased in the group B
      compared with those in the group A (111.3+/-22.8 vs 51.5+/-8.9, P<0.05). In
      addition, the endotoxin level in PVB was obviously increased in group B compared
      with that in the group A (76.8+/-9.1 vs 40.6+/-7.3, P<0.01) and reduced to the
      baseline at 48 h (group C). CONCLUSION: Severely disturbed gut flora in rats with
      GalN-induced acute liver failure plays an important role in the elevation of
      endotoxin level in PVB.

PMID- 15237441
TI  - Effect of extracts of trichosanthes root tubers on HepA-H cells and HeLa cells.
AB  - AIM: To investigate the cytotoxic activity of extracts of trichosanthes root
      tubers (EOT) on HepA-H cells and HeLa cells compared with trichosanthin (TCS),
      and to explore the possible mechanism of growth inhibitory effect of EOT on HeLa
      cells. METHODS: Tumor cells were cultured in vitro, and then microculture
      tetrzoalium assay (MTT) was used to investigate drugs' cytotoxic activity.
      Scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      were used to observe ultrastructural changes of cells, and electrophoresis was
      performed to detect changes of biochemical characteristics of intercellular DNA.
      RESULTS: TCS and EOT had no obvious effects on HepA-H cells (P>0.05), but had
      remarkable effects on HeLa cells in a time and dose dependent manner (r>0.864,
      P<0.05 or P<0.01). The inhibitory rate of EOT was much higher than that of TCS
      (P<0.01). Median inhibitory rates (IC50) of TCS and EOT on HeLa cells were 610.9
      mg/L and 115.6 mg/L for 36 h, and 130.7 mg/L and 33.4 mg/L for 48 h respectively.
      Marked morphologic changes were observed including microvillus disappearance or
      reduction, cell membrane bledding, cell shrinkage, condensation of chromosomes
      and apoptotic bodies with complete membranes. Meanwhile, apoptosis of HeLa cells
      was confirmed by DNA ladder formation on gel electrophoresis. CONCLUSION: TCS and
      EOT have no obvious effects on HepA-H cells, but have significant inhibitory
      effects on HeLa cells, indicating that EOT is superior to TCS in anti-tumor
      activity.

PMID- 15237442
TI  - Role of COX-2 in microcirculatory disturbance in experimental pancreatitis.
AB  - AIM: To elucidate the role of COX-2 in the development of capillary leakage in
      rats with acute interstitial pancreatitis. METHODS: Rats with acute interstitial
      pancreatitis were induced by caerulein subcutaneous injection. Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to determine the gene
      expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay
      the parameters of acute pancreatitis such as the serum amylase and plasma
      myeloperoxidase, and determination of capillary permeability in the pancreas by
      quantifying the permeability index (PI) assisted response of pancreatic
      microvascular via intravital fluorescence microscope video image analysis system.
      RESULTS: A significant increase of COX-2 expression, elevation of serum amylase,
      and plasma myeloperoxidase were detected in rats with acute edematous
      pancreatitis compared with control rats. The changes of pancreatic microvascular
      after caerulein injection were as following: (a) the decrease of pancreatic
      capillary blood flow (4th h, 0.56+/-0.09 nL/min, P<0.05; 8 th h, 0.34+/-0.10
      nL/min, P<0.001); (b) reduction of functional capillary density (4 th h, 381+/-9
      cm(-1), P>0.05; 8th h, 277+/-13 cm(-1), P<0.001); (c) irregular and intermittent
      capillary perfusion was observed at the 8th h and these vessels were also prone
      to permeation. CONCLUSION: COX-2 plays an important role in mediating capillary
      permeability in pancreatitis, thereby contributing to capillary leakage.

PMID- 15237443
TI  - Management of carbon tetrachloride-induced acute liver injury in rats by
      syngeneic hepatocyte transplantation in spleen and peritoneal cavity.
AB  - AIM: Acute hepatitis may seldom have a fulminant course. In the treatment of this
      medical emergency, potential liver support measure must provide immediate and
      sufficient assistance to the hepatic function. The goal of our study was to study
      the adequacy of hepatocyte transplantation (HCTx) in two different anatomical
      sites, splenic parenchyma and peritoneal cavity, in a rat model of reversible
      acute hepatitis induced by carbon tetrachloride (CCl(4)). METHODS: After CCl(4)
      intoxication, 84 male Wistar rats used as recipients were divided in to four
      experimental groups accordingly to their treatment: Group A (n=24): intrasplenic
      transplantation of 10x10(6) isolated hepatocytes, Group B (n=24): intraperitoneal
      transplantation of 20x10(6) isolated hepatocytes attached on plastic
      microcarriers, Group C (n=18): intrasplenic injection of 1 mL normal saline (sham
      operated controls), Group D (n=18): intraperitoneal injection of 2.5 mL normal
      saline (sham-operated controls). Survival, liver function tests (LFT) and
      histology were studied in all four groups, on d 2,5 and 10 post-HCTx. RESULTS:
      The ten-day survival (and mean survival) in the 4 groups was 72.2% (8.1+/-3.1),
      33.3% (5.4+/-3.4), 0% (3.1+/-1.3) and 33.3% (5.4+/-3.6) in groups A, B, C, D,
      respectively (P(AB)<0.05, P(AC)<0.05, PBD=NS). In the final survivors, LFT
      (except alkaline phosphatase) and hepatic histology returned to normal,
      independently of their previous therapy. Viable hepatocytes were identified
      within splenic parenchyma (in group A on d 2) and both in the native liver and
      the fatty tissue of abdominal wall (in group B on d 5). CONCLUSION: A
      significantly better survival of the intrasplenically transplanted animals has
      been demonstrated. Intraperitoneal hepatocytes failed to promptly engraft. A
      different timing between liver injury and intraperitoneal HCTx may give better
      results and merits further investigation.

PMID- 15237444
TI  - Bridging PCR and partially overlapping primers for novel allergen gene cloning
      and expression insert decoration.
AB  - AIM: To obtain the entire gene open reading frame (ORF) and to construct the
      expression vectors for recombinant allergen production. METHODS: Gene fragments
      corresponding to the gene specific region and the cDNA ends of pollen allergens
      of short ragweed (Rg, Ambrosia artemisiifolia L.) were obtained by pan-degenerate
      primer-based PCR and rapid amplification of the cDNA ends (RACE), and the
      products were mixed to serve as the bridging PCR (BPCR) template. The full-length
      gene was then obtained. Partially overlapping primer-based PCR (POP-PCR) method
      was developed to overcome the other problem, i.e., the non-specific amplification
      of the ORF with routine long primers for expression insert decoration. Northern
      blot was conducted to confirm pollen sources of the gene. The full-length coding
      region was evaluated for its gene function by homologue search in GenBank
      database and Western blotting of the recombinant protein Amb a 8(D106) expressed
      in Escherichia coli pET-44 system. RESULTS: The full-length cDNA sequence of Amb
      a 8(D106) was obtained by using the above procedure and deduced to encode a 131
      amino acid polypeptide. Multiple sequence alignment exhibited the gene D106
      sharing a homology as high as 54-89% and 79-89% to profilin from pollen and food
      sources, respectively. The expression vector of the allergen gene D106 was
      successfully constructed by employing the combined method of BPCR and POP-PCR.
      Recombinant allergen rAmb a 8(D106) was then successfully generated. The
      allergenicity was hallmarked by immunoblotting with the allergic serum samples
      and its RNA source was confirmed by Northern blot. CONCLUSION: The combined
      procedure of POP-PCR and BPCR is a powerful method for full-length allergen gene
      retrieval and expression insert decoration, which would be useful for recombinant
      allergen production and subsequent diagnosis and immunotherapy of pollen and food
      allergy.

PMID- 15237446
TI  - Helicobacter pylori infection in patients with autoimmune thrombocytopenic
      purpura.
AB  - AIM: To compare the prevalence of Helicobacter pylori (H pylori) infection in
      autoimmune thrombocytopenic purpura (AITP) patients with that of
      nonthrombocytopenic controls, and to evaluate the efficacy of the treatment in H
      pylori(+) and H pylori(-) AITP patients. METHODS: The prevalence of gastric H
      pylori infection in 38 adult AITP patients (29 female and 9 male; median age 27
      years; range 18-39 years) who consecutively admitted to our clinic was
      investigated. RESULTS: H pylori infection was found in 26 of 38 AITP patients
      (68.5%). H pylori infection was found in 15 of 23 control subjects (65.2%). The
      difference in H pylori infection between the 2 groups was not significant.
      Thrombocyte count of H pylori-positive AITP patients was significantly lower than
      that of H pylori-negative AITP patients (P<0.05). Thrombocyte recovery of H
      pylori-positive group was less than that of H pylori-negative group (P<0.05).
      CONCLUSION: H pylori infection should be considered in the treatment of AITP
      patients with H pylori infection.

PMID- 15237445
TI  - Cloning and expression of mouse peroxiredoxin I in IEC-6 Cells.
AB  - AIM: To clone and express mouse peroxiredoxin I in IEC-6 cells. METHODS: Total
      RNAs were isolated from cultured IEC-6 cells, and the coding region of
      peroxiredoxin I was amplified by RT-PCR. After it was cloned into T-vector and
      sequenced, pSG5 was used to transiently express peroxiredoxin I in IEC-6 by
      liposome-mediated transfection, and the expression of peroxiredoxin I was
      evaluated by RT-PCR and Western blot. RESULTS: A DNA fragment about 750 bp was
      amplified from total RNAs of IEC-6 cells using specific primers of peroxiredoxin
      I. The sequencing confirmed the coding region was successfully cloned into T
      vector, which was completely coincident with the sequence in GeneBank. After the
      EcoRI-BamHI fragment of T-vector containing peroxiredoxin I was inserted into
      pSG5, the recombinant plasmid was transferred to IEC-6 cells. RT-PCR assay showed
      that a DNA fragment of 930 bp could be amplified, which indicated the
      transcription of pSG5-Prx. Western blot confirmed the expression of peroxiredoxin
      I in IEC-6 cells. CONCLUSION: Mouse peroxiredoxin I can be successfully expressed
      in IEC-6 cells.

PMID- 15237447
TI  - Curative effects of interferon-alpha and HLA-DRB1 -DQA1 and -DQB1 alleles in
      chronic viral hepatitis B.
AB  - AIM: To investigate the association between curative effects of interferon-alpha
      and partial human leucocyte antigen (HLA) II alleles in chronic viral hepatitis
      B. METHODS: Sixty patients with chronic viral hepatitis B in Shanghai were
      treated with a standard course of treatment with interferon-alpha for 6 mo. HLA
      DRB1, -DQA1, and -DQB1 alleles were detected by polymerase chain reaction
      sequence specific primer (PCR-SSP) method. RESULTS: Frequencies of HLA-DRB1*04
      (P<0.025) and HLA-DQA1*0303 (P<0.01) in non-responders were significantly higher
      than those in partial and complete responders. Frequencies of HLA-DQA1*0505
      (P<0.025) and HLA-DQB1*0301 (P<0.005) in partial and complete responders were
      significantly higher than those in non-responders. CONCLUSION: Non-response to
      interferon-alpha therapy is positively correlated with HLA-DRB1*04 and HLA
      DQA1*0303, and negatively correlated with HLA-DQA1*0505 and -DQB1*0301 in patient
      with chronic viral hepatitis B. HLA II genes of the identification alleles
      provide a method for evaluating outcome of interferon-alpha treatment.

PMID- 15237448
TI  - Expansion and activation of natural killer cells from PBMC for immunotherapy of
      hepatocellular carcinoma.
AB  - AIM: To induce efficient expansion of natural killer (NK) cells from peripheral
      blood mononuclear cells (PBMCs) using a culture of anchorage-dependent Wilms
      tumor cell lines, and to provide a reliable supply for adoptive immunotherapy of
      hepatocellular carcinoma. METHODS: Culture expansion of NK cells was achieved
      using PBMCs cultured with Wilms tumor cells. Cytotoxicity was measured using a
      standard (51)Cr release assay and crystal violet staining technique. The
      proportions of CD3+, CD4+, CD8+, CD16+, and CD56+ cells were determined by flow
      cytometry. RESULTS: After PBMCs from healthy donors and hepatocellular carcinoma
      (HCC) were cultured with irradiated HFWT cells for 10-21 d, CD56+ CD16+ cells
      shared more than 50% of the cell population, and more than 80% of fresh HFWT
      cells were killed at an effector/target ratio of 2 over 24 h. NK-enriched
      lymphocyte population from HCC patients killed HCC-1 and 2 cells with
      sensitivities comparable to fresh TKB-17RGB cells. HCC cells proliferated 196
      fold with the irradiated HFWT cells at 18 d. Stimulation by HFWT cells required
      intimate cell-cell interaction with PBMC. However, neither the soluble factors
      released from HFWT cells nor the fixed HFWT cells were effective for NK
      expansion. The lymphocytes expanded with IL-2 killed fresh HFWT target cells more
      effectively than the lymphocytes expanded with the 4-cytokine cocktail (IL-lbeta,
      IL-2, IL-4 and IL-6). IL-2 was the sole cytokine required for NK expansion.
      CONCLUSION: Wilms tumor is sensitive to human NK cells and is highly efficient
      for selective expansion of NK cells from PBMCs.

PMID- 15237449
TI  - Intestinal colonization with Candida albicans and mucosal immunity.
AB  - AIM: To observe the relationship between intestinal lumen colonization with
      Candida albicans and mucosal secretory IgA (sIgA). METHODS: A total of 82
      specific-pathogen-free mice were divided randomly into control and colonization
      groups. After Candida albicans were inoculated into specific-pathogen-free mice,
      the number of Candida albicans adhering to cecum and mucosal membrane was
      counted. The lymphocyte proliferation in Peyer's patch and in lamina propria was
      shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch
      in Peyer's patch was investigated. IgA plasma cells in lamina propria were
      observed by immunohistochemical staining. Specific IgA antibodies to Candida
      albicans were measured with ELISA. RESULTS: From d 3 to d 14 after Candida
      albicans gavaging to mice, the number of Candida albicans colonizing in lumen and
      adhering to mucosal membrane was sharply reduced. Candida albicans translocation
      to mesenteric lymph nodes occurred at early time points following gavage
      administration and disappeared at later time points. Meanwhile, the content of
      specific IgA was increased obviously. Proliferation and differentiation of
      lymphocytes in lamina propria were also increased. CONCLUSION: Lymphocytes in
      lamina propria play an important role in intestinal mucosal immunity of specific
      pathogen-free mice when they are first inoculated with Candida albicans. The
      decreasing number of Candida albicans in intestine is related to the increased
      level of specific IgA antibodies in the intestinal mucus.

PMID- 15237450
TI  - Multidetector CT in evaluating blood supply of hepatocellular carcinoma after
      transcatheter arterial chemoembolization.
AB  - AIM: To assess the value of multidetector-row computed tomography (MDCT) in
      choosing retreatment methods of hepatocellular carcinoma (HCC) through evaluating
      the blood supply of low-density area of HCC after transcatheter arterial
      chemoembolization (TACE). METHODS: Thirty-two patients with HCC after TACE
      treatment were examined by plain scanning and hepatic multidetector-row CT. The
      location of low-density area on plain scanning and the enhancement patterns on
      dynamic contrast-enhanced scanning were observed. At the same time, three
      dimensional CT (3D CT) models of the volume rendering, curved multiplanar
      reformations, surface shaded display and maximum intensity projection
      reconstruction of the hepatic artery and portal vein were performed in 6 cases.
      RESULTS: In CT plain scanning data, low density areas of 32 cases of HCC after
      TACE treatment were divided into three types: peripheral, one-side-located and
      mixed types. In contrast-enhanced CT scans, the blood supply of low-density area
      was classified into four types: arterial blood supply (20 cases), portal blood
      supply (5 cases), arterial combined with portal blood supply (5 cases) and poor
      blood supply (2 cases). In 6 cases, the relationship between the low-density area
      and branches of hepatic artery as well as portal vein was shown by 3D CT.
      CONCLUSION: Hepatic MDCT is an effective method for evaluating the blood supply
      of low-density area and therapeutic effect of HCC after TACE treatment. Types of
      blood supply is helpful for the selection of retreatment.

PMID- 15237451
TI  - Multiple gene differential expression patterns in human ischemic liver: safe
      limit of warm ischemic time.
AB  - AIM: To investigate the multiple gene differential expression patterns in human
      ischemic liver and to produce the evidence about the hepatic ischemic safety
      time. METHODS: The responses of cells to hepatic ischemia and hypoxia at hepatic
      ischemia were analyzed by cDNA microarrary representing 4 000 different human
      genes containing 200 apoptotic correlative genes. RESULTS: There were lower or
      normal expression levels of apoptotic correlative genes during the periods of
      hepatic ischemia for 0-15 min, the maintenance homostatic genes were expressed
      significantly higher at the same time. But at the hepatic ischemia for 30 min,
      the expression levels of maintenance homeostatic genes were down-regulated, the
      expressions of many apoptotic correlative genes and nuclear transcription factors
      were activated and up-regulated. CONCLUSION: HIF-1, APAF-1, PCDC10, FBX5, DFF40,
      DFFA XIAP, survivin may be regarded as the signal genes to judge the degree of
      hepatic ischemic-hypoxic injure, and the apoptotic liver cell injury due to
      ischemia in different time limits. The safe limit of human hepatic warm ischemic
      time appears to be generally less then 30 min.

PMID- 15237452
TI  - A report of 28 cases of 3-year follow-up after liver transplantation for advanced
      hepatocellular carcinoma.
AB  - AIM: To investigate the therapeutic value of liver transplantation for advanced
      hepatocellular carcinoma (HCC). METHODS: Twenty-eight patients with advanced HCC
      were treated by liver transplantation from August 2000 to October 2003 at Peking
      University Third hospital. All the patients were followed up to evaluate the
      result. RESULTS: The longest follow-up duration was 3 years and 3 mo. Till the
      end of the follow-up period, 17 patients had already died and 11 were alive. Of
      those who died, 10 patients died of tumor recurrence, 4 died during the
      perioperative period, 2 died of variceal bleeding, and 1 died of biliary
      complication. According to life table method, the 1-, 2-, and 3-year survival
      rates were 87.5%, 52.5%,and 42.9%, respectively. CONCLUSION: Liver
      transplantation provides a new treatment under the circumstance of lacking of an
      effective treatment for advanced HCC at present. Some patients can survive for a
      relatively long time free of tumor. In our country, if the patients can afford
      liver transplantation, advanced HCC without extrahepatic metastasis is an
      indication for liver transplantation at present.

PMID- 15237454
TI  - Inhibition of growth and metastasis of human gastric cancer implanted in nude
      mice by d-limonene.
AB  - AIM: To investigate the effects and mechanism of d-limonene on the growth and
      metastasis of gastric cancer in vivo. METHODS: Metastatic model simulating human
      gastric cancer was established by orthotopic implantation of histologically
      intact human tumor tissue into gastric wall of nude mice. One percent d-limonene
      was orally administered at dose of 15 ml/kg every other day for seven weeks.
      Eight weeks after implantation, tumor weight, inhibition rate, apoptotic index
      (AI), microvessel density (MVD), vascular endothelial growth factor (VEGF),
      variation of ultrastructure, and the presence of metastasis were evaluated,
      respectively, after the mice were sacrificed. RESULTS: The tumor weight was
      significantly reduced in 5-FU group (2.55+/-0.28 g), d-limonene group (1.49+/
      0.09 g) and combined treatment group (1.48+/-0.21 g) compared with the control
      group(2.73+/-0.23 g, P<0.05). In 5-FU group, d-limonene group, combined treatment
      group, the inhibition rates were 2.60%,47.58% and 46.84% and 0, respectively; AI
      was (3.31+/-0.33)%, (8.26+/-1.21)%, (20.99+/-1.84)% and (19.34+/-2.19)%,
      respectively; MVD was (8.64+/-2.81), (16.77+/-1.39), (5.32+/-4.26) and (5.86+/
      2.27), respectively; VEGF expression was (45.77+/-4.79), (41.34+/-5.41), (29.71+/
      8.92) and (28.24+/-8.55), respectively. The incidences of peritoneal metastasis
      also decreased significantly in 5-FU group(77.8%), d-limonene group (20.0%) and
      combined group (22.2%) compared with control group (100%) versus 62.5%,30% and
      22.2%) (P<0.05). Liver metastasis was also inhibited and the incidences decreased
      significantly in 5-FU group, d-limonene group and combined group than that in
      control group (87.5% vs 55.5%, 20.0% and 22.2% respectively)(P<0.05). The
      incidence of ascites in control group, 5-FU group, d-limonene group and combined
      group was 25.0%, 22.2%, 0, 0, respectively and 12.5%, 11.1% 0, 0, with respect to
      the metastasis rate to other organs. CONCLUSION: d-limonene has antiangiogenic
      and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and
      metastasis. Combination of d-limonene with cytotoxic agents may be more
      effective.

PMID- 15237453
TI  - Clinical features, diagnosis, treatment and prognosis of multiple primary
      colorectal carcinoma.
AB  - AIM: To investigate the clinical features, diagnosis, treatment and prognosis of
      multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis
      of 37 patients with MPCC from 1974 to 1998 was carried out. RESULTS: The
      incidence of MPCC was 2.74%(37/1 348) in patients with primary colorectal
      carcinomas, 15 cases of them were patients with synchronous carcinomas (SC) and
      22 cases were diagnosed as metachronous carcinomas (MC). Most tumors were located
      in the right colon and rectum. Fifty-five percent (12/22) of MC were diagnosed
      within 3 years after tumor resection and 41%(9/22) of MC occurred after 8 years.
      Radical resections were performed in all patients except for 1 case. The 5-year
      survival rate of SC was 72.7%(8/11) and that of MC after the first cancer and
      second cancer was 71.4%(15/21) and 38.9%(7/18), respectively. CONCLUSION: The
      results indicate the importance of complete preoperative examination, careful
      intraoperative exploration and periodic postoperative surveillance. Early
      diagnosis and radical resection can increase survival rate of MPCC.

PMID- 15237455
TI  - Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic
      stent placement.
AB  - AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer
      after expandable metallic stent placement. METHODS: Ten cases of advanced
      esophageal cancer were evaluated, 7 having complete obstruction and 3 with
      digestive-respiratory fistula. Ten nitinol stents were placed at the site of
      stenosis. Patients were treated with a total dose of 1 200 cGy divided into 3
      fractions of 400 cGy 4-7 d after stents placement. RESULTS: All the 10 stents
      were placed successfully at one time. After radiotherapy for advanced esophageal
      cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean
      survival of 17 mo. No re-stenosis occurred among all the 10 cases. CONCLUSION:
      Stent placement combined with radiotherapy for esophageal cancer is helpful to
      prolong patients' survival and reduce occurrence of re-stenosis.

PMID- 15237456
TI  - Relationship between microvessel density and telomerase activity in
      hepatocellular carcinoma.
AB  - AIM: To study the relationship between microvessel density (MVD), telomerase
      activity and biological characteristics in hepatocellular carcinoma (HCC).
      METHODS: S-P immunohistochemical method and telomeric repeat amplification
      protocol (TRAP) were respectively used to analyze the MVD and telomerase activity
      in 58 HCC and adjacent normal tissues. RESULTS: The MVD in HCC with metastasis,
      lower differentiation or without intact capsule was significantly higher than
      that in HCC with intact capsule, higher differentiation, or without metastasis.
      While MVD had no relationship with tumor size, hepatic virus infection and other
      clinical factors. Telomerase activity was related to differentiation degree, but
      not to tumor size or histological grade. MVD in HCC with telomerase activity was
      higher than that in HCC without telomerase activity. CONCLUSION: MVD and
      telomerase activity may serve as diagnostic criteria of HCC in earlier stage.
      Meanwhile, there may be a cooperative effect between MVD and telomerase on the
      growth and metastasis of HCC.

PMID- 15237457
TI  - Treatment of severe Clonorchiasis sinensis by endoscopic nasobiliary drainage and
      oral praziquantel.
AB  - AIM: To assess the therapeutic value of endoscopic nasobiliary drainage (ENBD)
      and oral praziquantel for severe Clonorchiasis sinensis infection. METHODS: Of
      the 84 Clonorchiasis sinensis-infected patients enrolled, 58 were treated with
      ENBD (as observing group, ENBD group), 26 received operations (control group,
      operation group). Both of the two groups were comparable in terms of patient's
      age, body mass index. Before and one week after treatment, the average diameters
      of common bile ducts were measured by ultrasound, and serum bilirubin, ALP, gamma
      GT and ALT were detected by biochemical methods. After ENBD or operation, the
      patients took praziquantel for two days. RESULTS: Compared with the patients in
      operation group, ENBD patients in ENBD group had higher recovery rates of
      abdominal pain and fever as well as jaundice, quicker remission, smaller trauma,
      fewer complications and lower cost. CONCLUSION: ENBD combined with oral
      praziquantel is an effective and safe method for the treatment of severe
      Clonorchiasis sinensis.

PMID- 15237458
TI  - Benign nontraumatic inflammatory stricture of mid portion of common bile duct
      mimicking malignant tumor: Report of two cases.
AB  - Benign nontraumatic inflammatory stricture of the common bile duct (CBD) may
      result in obstructive jaundice, which can be misdiagnosed as a malignant tumor of
      the CBD preoperatively. Two cases with strictures of the mid portion of the
      common bile duct presenting with obstructive jaundice are reported herein.
      Preoperative radiological studies prompted us to confidently make the diagnosis
      of cholangiocarcinoma. However, the postoperative diagnosis on histological
      examination of the resected lesions was chronic inflammation and fibrosis. The
      complications of chronic duodenal ulcer are considered as the etiology of these
      two disorders.

PMID- 15237459
TI  - Intensive therapy for aggressive lymphoma.

PMID- 15237460
TI  - Intensive therapy for aggressive lymphoma.

PMID- 15237461
TI  - Intensive therapy for aggressive lymphoma.

PMID- 15237462
TI  - Adjuvant treatment of breast cancer with exemestane.

PMID- 15237463
TI  - Adjuvant treatment of breast cancer with exemestane.

PMID- 15237464
TI  - Acquired and inherited lipodystrophies.

PMID- 15237465
TI  - Biodiversity conservation: uncertainty in predictions of extinction risk.
AB  - Thomas et al. model species-distribution responses to a range of climate-warming
      scenarios and use a novel application of the species-area relationship to
      estimate that 15-37% of modelled species in various regions of the world will be
      committed to extinction by 2050. Although we acknowledge the efforts that they
      make to measure the uncertainties associated with different climate scenarios,
      species' dispersal abilities and z values (predictions ranged from 5.6% to 78.6%
      extinctions), we find that two additional sources of uncertainty may
      substantially increase the variability in predictions.

PMID- 15237467
TI  - The threat of iron overload. Too much of a good thing can cause serious heart
      problems.

PMID- 15237466
TI  - Biodiversity conservation: climate change and extinction risk.
AB  - Thomas et al. have carried out a useful analysis of the extinction risk from
      climate warming. Their overall conclusion, that a large fraction of extant
      species could be driven to extinction by expected climate trends over the next 50
      years, is compelling: it adds to the many other reasons why new energy policies
      are needed to reduce the pace of warming.

PMID- 15237468
TI  - Ask the doctors. After I had a heart attack, my cardiologist put me on aspirin. I
      need a procedure next month, and my surgeon told me stop my aspirin a week
      beforehand. Is there any risk to stopping?

PMID- 15237470
TI  - I need a heart catheterization. My cardiologist performs catheterizations, but
      doesn't do angioplasty or stents. Do you think I should find a cardiologist who
      does all these procedures?

PMID- 15237469
TI  - Ask the doctors. What's the difference between having a heart catheterization
      from the leg or from the arm? Which way is better?

PMID- 15237471
TI  - Speech therapy. Regaining your voice.

PMID- 15237472
TI  - Health tips. Preventing falls around the house.

PMID- 15237473
TI  - High-fiber diet may lower diabetes risk.

PMID- 15237474
TI  - Nerve block can decrease pancreatic cancer pain.

PMID- 15237475
TI  - Anal and rectal problems. Set aside embarrassment, seek medical care.

PMID- 15237477
TI  - Vascular dementia. More than memory loss.

PMID- 15237476
TI  - Aldosterone. An important factor in heart failure treatment.

PMID- 15237478
TI  - Second opinion. I have tried the new over-the-counter drug Prilosec for my
      heartburn, and it was very helpful. The package says I should take it for only
      two weeks and that if my heartburn comes back after that, I should see my doctor.
      If Prilosec helps, why can't I keep taking it?

PMID- 15237479
TI  - I read recently that foods high in vitamin E may be more beneficial than
      supplements containing vitamin E. Please explain.

PMID- 15237480
TI  - [Retroperitoneoscopic partial nephrectomy by using microwave tissue coagulation].
AB  - Partial nephrectomy is widely accepted as a treatment for small renal cell
      carcinoma. However, the laparoscopic approach has not yet been considered as a
      standard procedure. We reviewed our 13 retroperitoneoscopic partial nephrectomies
      and 11 conventional open partial nephrectomies. We have used microwave tissue
      coagulation for retroperitoneoscopic surgery without renal pedicle clamping
      between December 1999 and May 2003. The mean operating time for the
      retroperitoneoscopic group was not significantly longer than that for
      conventional open surgery group (183 minutes vs 194 minutes). However, the mean
      blood loss for the retroperitoneoscopic group was less than that for the open
      group (143 ml vs 512 ml). Histologic evaluation revealed renal cell carcinoma in
      10 patients, angiomyolipoma in 2 patients, and lymphoangiomyomatosis in one
      patient for retroperitoneoscopic group and renal cell carcinoma in 11 patients
      for the conventional open surgery group. In addition, when compared with the
      historical control that had undergone conventional partial nephrectomy,
      laparoscopic cases had significantly shorter postoperative times to oral intake,
      ambulance, and discharge from hospital. Bowel injury, massive bleeding, urine
      leakage, and atelectasis occurred in one case each in retroperitoneoscopic
      surgery. Retroperitoneoscopic surgery in the case of massive bleeding was
      converted to open surgery. On the other hand, urine leakage and postoperative
      hemorrhage occurred in one case each in conventional open surgery.
      Retroperitoneoscopic partial nephrectomy by using microwave tissue coagulation is
      a useful and less invasive method, whereas this procedure is more challenging
      than open partial nephrectomy in terms of complications.

PMID- 15237481
TI  - [Preputial development in Japanese boys].
AB  - The natural course of preputial development is still not clearly understood. The
      preputial retractability was evaluated in 242 Japanese boys. The incidence of
      having a retractable prepuce gradually increased with age from 0% at age 1 year
      to 77% by the age of 11 to 15 years. In 48 boys, preputial development was
      followed up for 2 to 10 years with the self-retract maneuver. Non-retractable
      prepuce was found in 9 boys, which then became retractable within 2-7 years. The
      prepuce became retractable in most of the boys with balanoposthitis. In
      conclusion, forced retraction or circumcision is unnecessary for phimosis in boys
      with or without balanoposthitis.

PMID- 15237482
TI  - [Etiology of nocturia and clinical efficacy of naftopidil on nocturia in patients
      with benign prostatic hyperplasia--analysis of frequency volume charts].
AB  - The etiology of nocturia in 70 patients with benign prostatic hyperplasia (BPH)
      who had nocturia of two or more times were examined based on frequency volume
      charts (FVC). Nocturia was classified into four groups: nocturnal polyuria, low
      capacity, combined nocturia, and no evidence of abnormality. Nearly half of the
      cases had nocturnal polyuria only. A little under 70% of patients had associated
      nocturnal polyuria (nocturnal polyuria+combined nocturia). Naftopidil was
      administered for three months to the patients with BPH who had nocturia with a
      urinary frequency of two or more times. Clinical efficacy was evaluated in 32
      patients based on FVC and naftopidil was shown to improve nocturia. The
      improvement in nocturia was determined by the increment in voided volume.

PMID- 15237483
TI  - [A case of emphysematous pyelonephritis successfully treated by transurethral
      retrograde drainage].
AB  - A 59-year-old female was referred to our institute for urinary tract infection
      with septicemia, thrombocytopenia, and hyperglycemia. Plain abdominal X-ray and
      computed tomography (CT) showed emphysema at the left renal parenchyma and
      urinary tract along with the perirenal inflammatory changes. These findings
      suggested emphysematous pyelonephritis in the early phase of occurrence in a
      diabetic patient. Transurethral catheterization of the left ureter was
      immediately performed, and occluded cloudy urine was drained. Ureteral stent was
      left indwelt transurethrally for easy accession in case of occlusion. E. coli was
      cultured in drained urine. Administration of antibiotics, insulin, and anti
      coagulant was performed, and drained urine became clear in several hours. General
      condition and laboratory findings were improved normally in a week, and CT did
      not reveal the emphysematous change of the left renal unit at the 11th hospital
      day.

PMID- 15237484
TI  - [A case of sarcomatoid carcinoma of the urinary bladder with brain metastasis: a
      case report].
AB  - A 69-year-old female visited our hospital with a chief complaint of macroscopic
      hematuria. A non-papillary broad-based tumor was found by cystoscopy. Excretory
      urography and computerized tomography revealed a large invasive tumor in the left
      wall of the urinary bladder. The histopathological diagnosis of bladder tumor
      obtained by transuretheral resection (TUR-Bt) was a sarcomatoid carcinoma
      composed of a urothelial cell carcinoma. One month after TUR-Bt, abdominal wall
      metastases were found. Thus total 50Gy of irradiation therapy was performed.
      However brain metastasis was also found and she died 3 months after TUR-Bt.

PMID- 15237485
TI  - [Spontaneous rupture of infected renal cyst presenting sudden onset of right
      flank distension: a case report].
AB  - A 21-year-old woman was referred to our hospital for sudden onset of right flank
      distension. Ultrasonography, abdominal CT scan and MRI revealed a giant cyst 20 x
      11 x 10 cm on the right kidney. Percutaneous puncture of the lesion was performed
      and fluid was drained. The fluid was yellowish and puriform. Gradually, the
      drainage fluid creatinine concentration increased. Cystography revealed
      communication between the lesion and the pyelocalyceal system. The patient
      underwent drainage for 25 days, causing the cyst to almost fully collapse. No
      recurrence has been detected in the follow-up for about 1 year. This case is the
      38th case of the rupture of a renal cyst reported in the Japanese literature. We
      reviewed 37 cases of rupture of renal cysts previously reported in Japan.

PMID- 15237486
TI  - [Testicular cancer with inferior vena caval embolus causing pulmonary embolism
      following chemotherapy: a case report].
AB  - A 21-year-old male presented with right scrotal discomfort. Right high
      orchiectomy revealed non-seminoma and he was diagnosed with stage I non-seminoma.
      Since acute myeloid leukemia (AML) was diagnosed incidentally, no adjuvant
      therapy was given and he received chemotherapy for AML. One year later, he
      complained of lumbago and general malaise. Complete remission of AML had been
      achieved and bone marrow puncture revealed no signs of recurrence. Computed
      tomography showed retroperitoneal lymph node swelling, inferior vena caval
      embolus distal to the hepatic vein, and multiple lung nodules. Metastasis of
      testicular neoplasm was suspected and chemotherapy with Bleomycin, Etoposide, and
      Cisplatin was started. On the fourth day of chemotherapy, the patient complained
      of sudden dyspnea and acutely went into shock. Pulmonary embolism was diagnosed
      and an inferior vena cava filter was placed. Chemotherapy was continued for four
      courses and the tumor showed complete remission. He has been free of disease for
      24 months. In rare cases of testicular cancer with inferior vena caval embolus,
      the physician should be aware of the possibility of causing pulmonary embolism
      after chemotherapy.

PMID- 15237487
TI  - [A case of idiopathic retroperitoneal fibrosis with a marked thickening of the
      urinary bladder wall].
AB  - The patient was a 49-year-old male with the chief complaint of right lower
      extremity edema. Ultrasonography showed a right hydronephrosis and a thickening
      of the right side of bladder wall. No bladder tumor was found by cystoscopy. The
      right renal pelvis and ureter were not visualized by drip infusion pyelography
      (DIP). Computed tomography (CT) demonstrated a soft tissue mass surrounding the
      bilateral common iliac artery and extending to thickened bladder wall. After the
      echo-guided needle biopsy, steroid therapy was performed under the diagnosis of
      the idiopathic retroperitoneal fibrosis. Prednisolone was administered for 10
      weeks, resulting in the complete disappearance of thickening of the bladder wall.

PMID- 15237489
TI  - [Fournier's gangrene: report of 4 cases].
AB  - Fournier's gangrene is an infective necrotizing fasciitis of the perineal,
      genital or perianal region. We treated four cases of Fournier's gangrene from
      July 2002 to April 2003. All patients were male, ranging in age from 73-92 years
      old (80.5 +/- 6.5). They were admitted to our hospital complaining of perineal
      pain, scrotal swelling and high fever. Immediately, we started systemic
      chemotherapy with broad-spectrum antibiotics, and performed surgical debridements
      for all patients. Three patients made a full recovery, but one patient died of
      sepsis. These cases are presented with some notes on the relevant literature.

PMID- 15237488
TI  - [Transitional cell carcinoma in prostate after intravesical instillation of
      Bacillus Calmette-Guerin].
AB  - We report 3 cases of prostatic involvement of transitional cell carcinomas
      (TCCs). All cases presented positive urinary cytology after intravesical
      instillation of Bacillus Calmette-Guerin (BCG) and then random biopsy of bladder
      and transurethral resection (TUR)-biopsy of prostatic urethra were performed. TUR
      biopsy demonstrated TCC in the prostate, although random biopsy failed to detect
      tumors in the bladder in all cases. Case 1 was treated with cystourethrectomy
      with ileal conduit, case 2 was treated with cystourethrectomy with bilateral
      ureterocutaneostomy and case 3 was treated with cystectomy with orthotopic ileal
      neobladder reconstruction. All cases are alive with no evidence of disease. TUR
      biopsy of prostatic urethra should be perfomed when patients present positive
      urinary cytology after BCG instillation therapy, because prostatic involvement of
      TCC associated with bladder carcinoma in situ is not rare.

PMID- 15237490
TI  - [A case of primary signet ring cell carcinoma of the urinary bladder presenting
      as nocturnal incontinence].
AB  - This is a report of our experience of a case of primary signet ring cell
      carcinoma of the urinary bladder. The patient was a 56-year-old man who was
      referred to our hospital presenting with incontinence and lumbago. A drip
      infusion pyelography study indicated bilateral hydronephrosis and a contracted
      bladder. Signet ring cell carcinoma was observed in the bladder submucosa after
      the second transurethral biopsy set. No other cancer lesions could be identified
      even after careful examination. Therefore, it was diagnosed as a primary signet
      ring cell carcinoma of the bladder. Total cystectomy with bilateral uretero
      cutaneostomy reconstruction was performed. The pathological stage was T4bN0M0 and
      the surgical margin was positive at the site of the pubic bone. Adjuvant therapy
      was not given. There was no evidence of disease 20 months after the operation. In
      Japan, this is the third case of primary signet ring cell carcinoma of the
      bladder presenting as incontinence.

PMID- 15237491
TI  - [A case of vesical paraganglioma with intrapelvic multiplicity].
AB  - A 35-year-old woman, who had a past history of hypertension due to paraganglioma
      of the urinary bladder and in the pelvis, was referred to us 12 years after the
      initial diagnosis of paraganglioma. Before coming to us and during the follow-up
      after enucleation of myoma uteri, she was again diagnosed as having a bladder
      tumor by a gynecologist. Cystoscopy revealed a non-papillary broad-based tumor,
      measuring 2 cm in diameter, on the trigone of the urinary bladder. Magnetic
      resonance imaging also showed two solid tumors, each measuring 2 cm in diameter,
      on the bilateral peri-vesical sides in the pelvis. Endocrinologic examination
      disclosed increased levels of serum and urinary catecholamines. Histopathologic
      examination revealed that the bladder tumor specimen obtained by transurethral
      resection was paraganglioma. She underwent partial cystectomy and resection of
      these intrapelvic tumors via a retroperitoneal approach. These tumors were
      histopathologically diagnosed as multiple paragangliomas. She has been followed
      up for 10 months after operation without any evidence of recurrence. Herein, we
      report this rare case of vesical paraganglioma and present a brief review of the
      relevant literature.

PMID- 15237492
TI  - [A case of ammonium urate urinary stone].
AB  - An 18-year-old female, who had undergone antireflux surgery for bilateral
      vesicoureteral reflux 5 years ago, was admitted to our department with complaints
      of fever and left-sided back pain. Bilateral renal stones and pyelonephritis were
      diagnosed after roentgenography, ultrasonography and urinalysis. Pyelonephritis
      was successfully treated with antibiotics and the left renal stone was completely
      disintegrated with extracorporeal shock wave lithotripsy. Spectrophotometric
      analysis revealed that the stone was composed of pure ammonium urate (AU). The
      patient had not experienced any episodes of urinary tract infection from the
      antireflux surgery until the present event, but had lost 20 kg in body weight
      during the last year due to a low-caloric diet and laxative abuse. AU urinary
      stones have been infrequently reported in Japan, and they are supposed to be
      associated with a low-caloric diet, laxative abuse, and anorexia nervosa.

PMID- 15237493
TI  - [A case of superior mesenteric artery syndrome after left nephrectomy].
AB  - Postoperative superior mesenteric artery syndrome is a rare complication of left
      nephrectomy. We treated a case of superior mesenteric artery syndrome that
      occurred 7 days after radical left nephrectomy for renal cell carcinoma. The
      patient was a 54-year-old Japanese man who presented with gross hematuria.
      Abdominal computed tomography showed a 3.8 x 3.8 x 5 cm heterogeneous cystic mass
      in the left kidney. Transperitoneal left radical nephrectomy was performed
      because renal cell carcinoma was suspected. The patient resumed oral intake 3
      days after surgery, but he began vomiting repeatedly from the 7th day after
      surgery. Gastroduodenography showed an abrupt vertical linear obstruction of the
      third portion of the duodenum. Superior mesenteric artery syndrome was diagnosed.
      Conservative therapy (indwelling nasogastric tube, intravenous hyperalimentation
      and postural changes) was effective.

PMID- 15237494
TI  - National bullying prevention campaign gains momentum.

PMID- 15237495
TI  - Living with the plagues.

PMID- 15237498
TI  - [Psychiatric inpatient care and sexuality].
AB  - BACKGROUND: Although sexuality has implications for psychiatric services, there
      is little research about ,,psychiatric in-patient care and sexuality". METHOD:
      Pertinent psychiatric literature published since 1970 was reviewed
      comprehensively. Recurring themes were identified, and were discussed in terms of
      historical trends and conceptual contradictions. RESULTS: Papers discussing
      sexuality and its relevance to psychiatric services can be summarised under three
      conceptual headings: (1) sexuality as taboo, (2) normalisation/empowerment, and
      (3) problematisation. The three clusters of papers focusing on these aspects were
      consecutive in time. DISCUSSION: During the 1970s and 1980s patients' equal
      rights to sexuality were weighed against moralistic concerns. Currently,
      patients' sexuality is discussed against the background of potentially negative
      consequences for the individual patient. A discussion is needed that encompasses
      this dilemma in order to find ways towards adequate practical handling of the
      issue of patients' sexuality in psychiatric services.

PMID- 15237499
TI  - [Long approach, short jump: "integrated care" according to GMG (health care
      modernization regulation)].

PMID- 15237500
TI  - [Public Health Administrators' Conference, July 2003].

PMID- 15237501
TI  - Abstracts of the 2nd Joint Scientific Meeting of the American Pain Society and
      the Canadian Pain Society. May 2004.

PMID- 15237502
TI  - Abstracts from the Chemotherapy Foundation Symposium XXI: Innovative Cancer
      Therapy for Tomorrow. November 12-15, 2003. New York, New York, USA.

PMID- 15237503
TI  - [Abstracts of the 20th Congress of the Hungarian Society of Endocrinology and
      Metabolism. 20-22 March 2004, Szolnok].

PMID- 15237505
TI  - Abstracts of the 56th Annual Meeting of the AACC. July 25-29, 2004, Los Angeles,
      California, USA.

PMID- 15237504
TI  - DNA ploidy analysis in histopathology. DNA ploidy studies in pathology-a critical
      appraisal.

PMID- 15237506
TI  - Abstracts of the Society of Obstetricians and Gynaecologists of Canada 60th
      Annual Clinical Meeting. June 25-29, 2004, Edmonton, Alberta, Canada.

PMID- 15237507
TI  - The illegality of abortion in Mexico.

PMID- 15237508
TI  - Fetal pain legislation: is it viable?

PMID- 15237509
TI  - Forgotten Supreme Court abortion cases: Drs. Hawker and Hurwitz in the deck and
      defrocked.

PMID- 15237511
TI  - Abstracts of the 51st Annual Meeting of the Society of Nuclear Medicine. June 19
      23, 2004, Philadelphia, Pennsylvania, USA.

PMID- 15237510
TI  - The naked clone.

PMID- 15237513
TI  - Abstracts from the World Congress on In Vitro Biology. May 22-26, 2004. San
      Francisco, California, USA.

PMID- 15237512
TI  - Telemedicine for multidisciplinary lung cancer meetings.
AB  - According to recent UK guidelines on the management of lung cancer, all cases
      should be reviewed prospectively by a lung cancer multidisciplinary team (MDT)
      and a thoracic surgeon should be readily available to liaise with the MDT.
      However, there is a shortage of thoracic surgeons in the UK. Over a one-year
      period, 28 MDT meetings were held at a district general hospital in Southend, at
      which 62 patients were presented to a tertiary cardiothoracic centre in London,
      80 km away, via ISDN videoconferencing at 384 kbit/s. The annual resection rate
      increased by 30% following the introduction of the telemedicine MDTmeetings, and
      the mean time from first being seen in the clinic to surgery was reduced from 69
      to 54 days.We estimate that the telemedicine meetings saved over three working
      weeks of thoracic surgical time during the year.

PMID- 15237514
TI  - A framework to assess the readiness for tele-ophthalmology of glaucoma patients
      living in isolated communities.

PMID- 15237515
TI  - Reliability of digital images when used to assess burn wounds.

PMID- 15237516
TI  - Abstracts from Scientific Sessions 2001. Anaheim, California, USA, November 11
      14, 2001.

PMID- 15237518
TI  - Abstracts of the IV Meeting of Brazilian Researchers on Alzheimer's Disease and
      Related Disorders, 2003.

PMID- 15237517
TI  - Dangerous patients: an exception to the federal psychotherapist-patient
      privilege.

PMID- 15237519
TI  - Excess embryos: is embryo adoption a new solution or a temporary fix?

PMID- 15237521
TI  - Abstracts of the 194th, 195th, 196th and 197th Meetings of the Dutch
      Ophthalmological Society, 2000-2003.

PMID- 15237522
TI  - Abstracts of the XX International Congress "The Fetus as a Patient" and the 6th
      Ian Donald Inter-University of Medical Ultrasound. Fukuoka, Japan, April 23-26,
      2004.

PMID- 15237520
TI  - Abstracts of the 2nd World Congress of Pediatric Gastroenterology, Hepatology and
      Nutrition. Paris, France, 2004.

PMID- 15237523
TI  - APICON 2004. Abstracts of the 59th Annual Conference of the Association of
      Physicians of India. January 18-21, 2004, Hyderabad.

PMID- 15237524
TI  - Francisco Jose de Goya y Lucientes (1746-1828). Self portrait with Doctor Arrieta
      (1820).

PMID- 15237525
TI  - Nature is complex: our orchestra seats at the most wonderful show on earth.

PMID- 15237526
TI  - [XXVI Congress of the Brazilian Society of Hemodynamics and Interventional
      Cardiology and the IX Meeting of Nursing. 9-11 June 2004, Joao Pessoa, Paraiba.
      Abstracts].

PMID- 15237528
TI  - Abstracts of the 8th Congress of the European Society of Contraception.
      Edinburgh, United Kingdom, June 2004.

PMID- 15237527
TI  - Abstracts from the American Society of Gene Therapy 7th Annual Meeting. June 2-6,
      2004, Minneapolis, Minnesota, USA.

PMID- 15237530
TI  - [Abstracts of the II Brazilian Congress on Cardiac Insufficiency. Sao Paulo,
      Brazil, 2003].

PMID- 15237531
TI  - Abstracts of the 2nd International Conference on Polyomaviruses and Human
      Diseases: Basic and Clinical Perspectives. 11-13 June 2004, Sapporo, Japan.

PMID- 15237529
TI  - Resolving the case of Terri Schiavo: a matter of being in a persistent vegetative
      state or of the patient's intent to forgo life-sustaining procedures?

PMID- 15237532
TI  - An opportunity lost.

PMID- 15237533
TI  - Wan Yanhai, Director of the Aizhixing Institute of Health Education.

PMID- 15237534
TI  - Abstracts of the 64th Scientific Sessions of the American Diabetes Association.
      June 4-8, 2004, Orlando, Florida, USA.

PMID- 15237535
TI  - Caribbean Health Research Council 49th Annual Council and Scientific Meetings.
      April 21-24, 2004, St George's, Grenada.

PMID- 15237537
TI  - Tourette's syndrome: a case example for mandatory genetic regulation of
      behavioral disorders.

PMID- 15237536
TI  - Patenting human life and the rebirth of the Thirteenth Amendment.

PMID- 15237538
TI  - Introduction: on the edges of informed consent.

PMID- 15237540
TI  - Scrutiny puts private healthcare data on a plate.

PMID- 15237539
TI  - The rhetoric of Kevorkian's battle.
AB  - Kenneth Burke's characterization of constitutions effectively describes the
      customs and values that are lived within a community, and he has well charted the
      dialectical process which such constitutions undergo when they actually submit to
      change. In this paper, the totality of thematically-relevant discursive events
      which arise during periods of constitutional amending are referred to, building
      from Bitzer, as a rhetorical situation. Using Bitzer alongside Burke, it will be
      shown that Jack Kevorkian's rhetorical intent, as expressed in his writings and
      public statements, is distinct from the rhetorical situation to which he has been
      assigned, illustrating the significant discrepancy between the would-be
      rhetorical utterances of a speaker and those utterances which have rhetorical
      impact. The argument will show how Kevorkian's intention to popularize obitiatry
      contrasts with his public image as a champion of physician-assisted dying.

PMID- 15237541
TI  - Implementation ideas. Oar inspiring.

PMID- 15237542
TI  - Cancer services: it's make or break for waiting-list targets.

PMID- 15237543
TI  - Cultural change ideas. From out of the ashes.

PMID- 15237544
TI  - Finger on the pulse. Interview by Nick Edwards.

PMID- 15237545
TI  - [Gastroesophageal reflux and chronic pharyngitis].

PMID- 15237547
TI  - Many hats. Execs on board gain insight, cash and criticism.

PMID- 15237546
TI  - Retirement community.
AB  - The daily stresses of managing a hospital or hospital system seem to be claiming
      more executives, with the recent exit of at least a half-dozen relatively young
      CEOs of prominent organizations--including Christopher Carney, left, of Bon
      Secours Health System. "I can think of no time when the demands on CEOs have been
      greater," says one association executive.

PMID- 15237548
TI  - Is the price right? Hospitals spend less on services but charge more.

PMID- 15237549
TI  - Summertime grilling. Lawmakers question WellPoint execs on bonuses.

PMID- 15237550
TI  - Second coming. New chain's success will depend on deals.

PMID- 15237551
TI  - For sale. Pa. hospital may buy itself back, block sale to rival.

PMID- 15237552
TI  - More work needed on workforce. Industry efforts are on target but they must be
      intensified as boomers retire.

PMID- 15237553
TI  - Workforce Report 2004. One answer: productivity. A worsening worker shortage
      forces providers to use IT, other efficiencies to meet demand.

PMID- 15237555
TI  - Workforce Report 2004. Minority hires still lagging.

PMID- 15237554
TI  - Workforce Report 2004. Ratio fight goes national. As Calif. adjusts, backers seek
      to replicate success.

PMID- 15237556
TI  - Workforce Report 2004. Taking initiative on training. Providers push expansion of
      nurse education.

PMID- 15237557
TI  - Workforce Report 2004. A threat to foreign workers. Changes to visa programs hit
      key staffing solution.

PMID- 15237558
TI  - Rewriting the rules. Transcriptionists, radiologists hear call for changes.

PMID- 15237559
TI  - Critics, supporters argue importation before HHS task force.

PMID- 15237560
TI  - Customization key to successful CPOE.

PMID- 15237561
TI  - Illinois affiliate uses grant to improve emergency-response network.

PMID- 15237562
TI  - Voluntary reporting system gauges Wisconsin hospital data.

PMID- 15237563
TI  - Bosentan therapy for pulmonary arterial hypertension.
AB  - PURPOSE: The etiology, epidemiology, pathophysiology, diagnosis, and
      manifestations of pulmonary arterial hypertension (PAH) are described, and the
      role of bosentan in the management of PAH is reviewed. SUMMARY: The incidence of
      primary pulmonary hypertension, a subcategory of PAH, is estimated to be one to
      two new cases per million people annually in the general population. PAH has
      definitively been linked with several appetite suppressants. Disease-induced
      causes of PAH include connective tissue diseases, portal hypertension or liver
      disease, and human immunodeficiency virus infection. The clinical diagnosis of
      early PAH is difficult because its symptoms are nonspecific. Exertional dyspnea,
      the most common symptom of PAH, occurs in 60% of patients and indicates a
      severely compromised cardiac output. Three dependent elements are integral to the
      development of elevated mean pulmonary arterial pressure and PAH: vascular wall
      remodeling, thrombosis in situ, and vasoconstriction. Bosentan undergoes
      extensive hepatic metabolism. Bosentan-induced hepatotoxicity is common and must
      be monitored carefully throughout therapy. Since PAH is common in women of
      childbearing age, the use of bosentan in these patients requires careful review.
      Limited data exist on the use of bosentan in children, but one small study found
      that treatment with the drug resulted in hemodynamic improvement for pediatric
      patients with PAH. CONCLUSION: Prostacyclin analogues are the most effective
      agents for managing PAH, but their use is hampered by the need for parenteral
      therapy. Oral bosentan is a novel treatment alternative for patients with PAH.
      Further trials are necessary to determine bosentan's onset of action,
      consistency, durability, and magnitude of effect in different populations with
      PAH and its impact on survival.

PMID- 15237564
TI  - Influence of time stress and other variables on counseling by pharmacists about
      antiretroviral medications.
AB  - PURPOSE: The medication counseling practices of pharmacists caring for patients
      with HIV infection and the factors influencing their counseling behaviors
      regarding antiretroviral medications were examined. METHODS: A questionnaire was
      mailed in February 2000 to pharmacist-managers of 573 ambulatory care pharmacies
      providing medications to beneficiaries of the North Carolina AIDS Drug Assistance
      Program. The frequency of and attitudes about adherence counseling for patients
      with HIV infection; the time allocated, spent, and needed to provide high-quality
      care to these patients; and pharmacists' time pressure and time stress were
      measured. RESULTS: Of the 573 questionnaires mailed, 440 (77%) were usable. Fifty
      nine percent of pharmacists reported that they did not have enough time to
      provide adherence counseling to patients receiving antiretroviral medications,
      and 45% reported that most of their patients did not receive such counseling.
      Time-stressed pharmacists were significantly less likely to perform 12 of 22
      counseling behaviors, including discussing adverse effects (13% versus 24%, p <
      0.0089), drug interactions (13% versus 31%, p < 0.0001), and what to do if a dose
      is missed (8% versus 23%, p < 0.0001). Multivariate analysis revealed that time
      stress, perceived skill and interest in adherence counseling, and job
      satisfaction were significantly associated with the counseling index. CONCLUSION:
      Time pressure and other barriers appeared to limit the care that some pharmacists
      offered to patients with HIV infection. Pharmacist age, job satisfaction, and
      perceived skill and interest in adherence counseling influenced the
      comprehensiveness of the counseling pharmacists provided for patients receiving
      antiretroviral medications.

PMID- 15237565
TI  - Investigation of correlation between house-staff work hours and prescribing
      errors.
AB  - PURPOSE: The possible correlation between the frequency and significance of
      prescribing errors and the number of hours worked during a 24-hour shift by
      hospital house staff was studied. METHODS: A prospective observational trial was
      conducted in two internal medicine units at an academic medical center. Orders
      written by medical house staff covering the study units between January 8 and
      March 10, 2001, were collected daily and evaluated for obvious prescribing
      errors, the type and significance of the errors, and the number of hours the
      resident had worked during a 24-hour shift at the time of the prescribing error.
      RESULTS: A total of 45,366 orders (including orders for medications, laboratory
      tests, diagnostic procedures, and nursing care) were entered on the study units
      during the study period. A total of 498 erroneous prescribing orders were
      identified. A majority of the erroneous orders (77%) could have resulted in
      significant morbidity or mortality had they reached the patient. The most common
      errors involved the wrong dose (18%), the wrong dosage frequency (15%), and
      duplicate orders (15%). There was no statistically significant correlation
      between the number of hours worked and the frequency or significance of the
      errors. CONCLUSION: The number of hours worked by medical house staff during a 24
      hour shift did not appear to affect the frequency or significance of their
      prescribing errors.

PMID- 15237566
TI  - Stability and compatibility of tegaserod from crushed tablets mixed in beverages
      and foods.
AB  - PURPOSE: The stability and compatibility of tegaserod from crushed tablets in
      selected beverages and foods were studied. METHODS: Suspensions of tegaserod
      maleate tablets containing 6 mg of the drug base were prepared by crushing the
      tablets and mixing the powder with tap water, apple juice, orange juice, milk,
      applesauce, yogurt, and chocolate-hazelnut spread. Drug stability, drug
      comparability, suspension homogeneity, and completeness of a dose were measured
      by high-performance liquid chromatography at intervals up to three days at 20-25
      degrees C and 5 degrees C. In vitro dissolution profiles were determined for
      crushed tegaserod tablets in water, apple juice, orange juice, and applesauce.
      RESULTS: Tegaserod from crushed tablets was stable in and compatible with water,
      apple juice, orange juice, and applesauce, and the suspensions were homogeneous.
      The complete dose was delivered with these media. The dissolution profiles of
      crushed tegaserod tablets in water and in apple juice were comparable to those of
      intact tablets; the dissolution profiles in orange juice and applesauce were not
      comparable with those of intact tablets. The results with milk, yogurt, and
      chocolate-hazelnut spread as vehicles were inconclusive. The suspension in milk
      was not homogeneous, and the dose was incomplete. CONCLUSION: Tegaserod from
      crushed tablets was stable in and compatible with water, apple juice, orange
      juice, and applesauce, but the dissolution profile in orange juice or applesauce
      was not acceptable. Apple juice may be the preferred vehicle because it masks the
      drug's taste.

PMID- 15237567
TI  - Increasing the safety of analgesia use in a community hospital.

PMID- 15237568
TI  - Development of an alcohol withdrawal delirium prophylaxis protocol in a community
      teaching hospital.

PMID- 15237569
TI  - Need for uniform national standards for the education and training of pharmacy
      technicians.

PMID- 15237570
TI  - Bioterrorism preparedness and response: emerging role for health-system
      pharmacists.

PMID- 15237571
TI  - New Zealand revisited.

PMID- 15237572
TI  - Hazardous medications.

PMID- 15237573
TI  - Counseling patients with myocardial infarction in India.

PMID- 15237574
TI  - Propofol as a drug of diversion.

PMID- 15237575
TI  - Interaction of warfarin with glucosamine--chondroitin.

PMID- 15237577
TI  - Smoking in Italy 2003, with a focus on the young.
AB  - AIMS AND BACKGROUND: To update trends in smoking prevalence in Italy to 2003,
      with specific focus on the young. METHODS: A population-based, face-to-face
      survey conducted in February-April 2003 on 3,535 individuals aged 15 or over,
      representative of the whole Italian adult population, plus an over sampling of
      426 subjects aged 15 to 24 years. RESULTS: Overall, 27.6% of Italians described
      themselves as current cigarette smokers (33.2% men, 22.5% women); 20.1% of men
      and 8.0% of women smoked 15 or more cigarettes per day. Ex-smokers were 16.6%
      (22.5% men, 11.2% women). No appreciable difference with reference to geographic
      area was observed. Less educated men, but more educated women, were more
      frequently smokers. As compared to previous years, no noticeable change was
      observed in overall smoking prevalence. However, an appreciable decline was
      observed in the young (15 to 24 years), from 37.6% in 2001 to 32.6% in 2003 for
      men, and from 30.4% to 20.7% for women. Among current smokers, 40.6% had tried at
      least once to stop. Of these, only 6.8% had used some pharmacological and 1.8%
      some psychological support. CONCLUSIONS: Overall self-reported smoking prevalence
      had not appreciably changed over the last few years. However, prevalence of
      smoking appears to have declined in the young. Compared to legal sale data,
      tobacco consumption is substantially under reported.

PMID- 15237576
TI  - HER-2/neu receptor in prostate cancer development and progression to androgen
      independence.
AB  - Development of prostate cancer and progression to androgen-independent disease is
      correlated with increased expression of growth factors and receptors capable of
      establishing autocrine and/or paracrine growth-stimulatory loops. A thorough
      review was made of the current literature and recent abstract presentations at
      scientific meetings focusing on the role of the HER-2/neu (c-erbB2) receptor in
      prostate cancer and the potential clinical usefulness of its specific inhibitors.
      In the past 10 years, conflicting results on HER-2/neu expression in prostate
      cancer have been reported. More recently, four studies have shown experimental
      evidence of HER-2/neu in the development of prostate cancer and, more
      specifically, in the progression to a hormone-refractory clinical behavior.
      Furthermore, it has been proposed that HER-2 family and androgen receptors
      function synergistically in the absence of androgen, which suggests a cross-talk
      between the HER-2/neu and androgen receptor pathways. Finally, clinical trials
      are in progress in prostate cancer patients to test novel agents that selectively
      interfere with HER-2/neu activity.

PMID- 15237578
TI  - Non-occupational risk factors for bladder cancer: a case-control study.
AB  - AIMS: The aim of this study was to determine non-occupational risk factors for
      bladder cancer in Serbia. METHODS AND DESIGN: A hospital-based, case-control
      study included 130 newly diagnosed bladder cancer patients and the same number of
      individually matched controls with respect to sex, age (+/- 2 years) and type of
      residence (rural or urban), from the Clinical Center of Serbia in Belgrade and
      from the Clinical Center in Kragujevac in central Serbia. The study took place
      from June 1997 to March 1999. RESULTS: According to multivariate logistic
      regression analysis, there was an association between: frequency of daily
      urination (OR = 0.18; 95% CI = 0.08-0.39); consumption of liver (OR = 13.81; 95%
      CI = 2.49-76.69), canned meat (OR = 8.38; 95% CI = 1.74-40.36), fruit juices (OR
      = 0.08; 95% CI = 0.01-0.56); the highest tertile of pork (OR = 4.55; 95% CI =
      1.30-15.93), cabbage (OR = 0.25; 95% CI = 0.06-1.01) and vinegar (OR = 4.41; 95%
      CI = 1.18-16.50) intake and risk for bladder cancer. CONCLUSIONS: Consumption of
      liver, canned meat, pork (h vs l tertile) and vinegar (m vs l tertile) was
      indicated as a risk factor for bladder cancer, whereas frequent daily urination,
      consumption of fruit juices and cabbage (h vs l tertile) were indicated as
      protective factors.

PMID- 15237579
TI  - Lung cancer mortality in a district of La Spezia (Italy) exposed to air pollution
      from industrial plants.
AB  - AIMS AND BACKGROUND: In the last decades, many epidemiological studies have
      implicated outdoor environmental carcinogens in the onset of lung cancer. The
      present investigation evaluated lung cancer mortality in two areas of the
      Province of La Spezia (Northern Italy) exposed to environmental pollution emitted
      by a coal-fired power station and other industrial sources, including a waste
      incinerator. METHODS: In the two exposed areas, lung cancer mortality risk for
      the 1988-1996 calendar period was evaluated using the whole Province population
      as referent. The corresponding relative risks (RR) were estimated after
      controlling for age structure, urban/rural gradient and deprivation factors
      (occupation, education, home ownership, housing conditions and family structure)
      by a Poisson regression modeling. The geographic pattern of risk for the whole
      province was evaluated via the Besag, York and Mollie (BYM) bayesian model.
      RESULTS: Persons living in urban areas showed the highest rates in both sexes. No
      statistically significant risk excess was found in the two exposed areas among
      males, after excluding rural and semi-rural zones from the analyses (RR = 1.03
      and RR = 0.77). In contrast, a risk excess was observed for females in both
      exposed areas, which remained elevated and statistically significant (P <0.05)
      after restriction to urban/semi-urban municipalities and after controlling for
      deprivation factors (RR = 1.54 and RR = 2.14, respectively). Bayesian mapping
      confirmed the rural/urban gradient and the risk excess observed in females near
      the industrial sites. CONCLUSIONS: The risk observed among females is consistent
      with pollution measurements and with other epidemiologic findings, whereas a
      strong confounding from occupational exposures and smoking habit could account
      for the lack of an excess risk in males. However, the ecologic nature of this
      investigation prevented drawing a causal inference. The pollution-related risk
      observed in the female gender is an important clue that deserves further
      epidemiologic attention.

PMID- 15237580
TI  - Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer.
AB  - AIMS AND BACKGROUND: As raltitrexed and oxaliplatin (L-OHP) are both effective in
      the treatment of colorectal cancer but have different mechanisms of action, we
      studied the antitumoral activity and safety of their combined use in patients
      with advanced colorectal cancer. METHODS: A 15-min intravenous infusion of
      raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were
      administered on day 1 every three weeks for a maximum of six cycles. RESULTS: The
      study involved 51 patients (27 males and 24 females) with a median age of 65
      years (range, 43-78); 28 were aged > or = 65 years. The primary tumor site was
      the colon in 35 patients and the rectum in 16. Thirty-four patients had received
      prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most
      frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8
      cases) and lymph nodes (3 cases). Twenty-four patients completed the entire
      treatment plan. The most common toxicities were transaminitis (16 patients, grade
      3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4),
      and asthenia (one patient, grade 3). The treatment was stopped in one patient
      because of prolonged grade 4 transaminitis. The adverse event profile was similar
      in the patients aged > 65 years and < 65 years. Complete responses were observed
      in 2 patients, partial responses in 12, stable disease in 23, and progression in
      8. CONCLUSIONS: The results of the study suggest that the raltitrexed plus
      oxaliplatin regimen is feasible and clinically active in advanced colorectal
      cancer.

PMID- 15237582
TI  - Serum interleukin-6 levels correlate with malnutrition and survival in patients
      with advanced non-small cell lung cancer.
AB  - AIM: To investigate the level of interleukin-6 in advanced non-small cell lung
      cancer and to analyze the relationship with malnutrition and survival. METHODS
      AND STUDY DESIGN: Seventy-one newly diagnosed advanced non-small cell lung cancer
      patients were enrolled in this prospective study. Malnutrition was defined by
      using subjective global assessment. Performance status was assessed by the
      Karnofsky scale. Serum levels of albumin, transferrin, C-reactive protein,
      lymphocytes/mm3, lactate dehydrogenase and growth hormone were determined before
      treatment. The patients were followed, and the factors affecting survival were
      analyzed. RESULTS: The mean follow-up after diagnosis was 180 days. IL-6 levels
      increased in 48 (68%) of 71 patients. According to the subjective global
      assessment, 28 (39%) patients were well nourished and 43 (61%) were malnourished.
      Of the 43 malnourished patients, 29 (41%) were moderately malnourished or
      suspected of being malnourished and 14 (20%) were severely malnourished. The IL-6
      level was related to impaired performance status (P = 0.0001), severe
      malnutrition (P = 0.004), increased C-reactive protein (P = 0.013), higher growth
      hormone (P = 0.025) and transferrin (P = 0.03) levels. On univariate analysis,
      impaired performance status, moderate and severe malnutrition, decreased serum
      albumin and transferrin, a raised IL-6 and lactate dehydrogenase levels were the
      significant prognostic factors for survival. Multivariate analysis indicated that
      a raised IL-6, severe malnutrition and a low serum level of albumin were
      independent prognostic factors for survival in patients with advanced non-small
      cell lung cancer. CONCLUSIONS: IL-6 secretion may play a role in the
      pathophysiology of malnutrition in advanced lung cancer. Results show a relation
      between elevated IL-6 serum levels and malnutrition, poor performance status,
      acute phase response and shorter survival in patients affected by advanced non
      small cell lung cancer.

PMID- 15237581
TI  - Treatment of metastatic pancreatic cancer with a combination of gemcitabine and 5
      fluorouracil: a single center phase II study.
AB  - AIM: To determine the activity and toxicity of a combination of weekly
      gemcitabine and 5-fluorouracil bolus intravenously in patients with metastatic
      pancreatic cancer. PATIENTS AND METHODS: Twenty-one patients with previously
      untreated metastatic pancreatic cancer were included in this phase II study. The
      schedule was gemcitabine (1000 mg/m2 i.v.) and 5-fluorouracil (500 mg/m2 bolus
      i.v.) weekly for 3 weeks every month. RESULTS: Four patients (19%) achieved a
      partial response and three stable disease. A clinical benefit was obtained in 7
      patients (33%). Median survival for all the patients was 6 months. The treatment
      was well tolerated and toxicity was mild. WHO grade 3 leukopenia occurred in 2
      (9.5%) patients, grade 3 anemia in 4 (19%) patients, grade 3-4 thrombocytopenia
      in 4 (19%) patients, grade 1 diarrhea in 1 (4.7%) patient and grade 1 mucositis
      in 3 (14.2%) patients. CONCLUSION: The weekly administration of gemcitabine
      combined with 5-fluorouracil bolus i.v. is an active and well-tolerated regimen
      in metastatic pancreatic cancer. However, its efficacy is relatively limited.

PMID- 15237584
TI  - Postoperative adjuvant radio(chemo)therapy for rectal cancer: an appraisal.
AB  - AIMS AND BACKGROUND: Rectal cancer can be considered a broad-spectrum disease,
      where the surgeon, radiation oncologist and medical oncologist have a peculiar
      and specific place in order to work harmoniously as a good orchestra. The reality
      in common general hospitals is far from that of comprehensive cancer centers,
      particularly for postoperative approaches. The adjuvant therapy of rectal cancer
      is not codified worldwide, and it is strongly dependent on preoperative staging
      procedures, surgeon's acts and pathologist's decisions. Starting from our 10-year
      experience, we analyzed the various steps of postoperative approaches, defining
      possible decision errors, the incongruity of some attitudes, and the lack of
      knowledge of recent achievements of science in this disease. METHODS: A total of
      194 patients with advanced surgically removed rectal cancer (pT3-4 pN0-any pT
      pN+) treated with postoperative radio(chemo)therapy was reviewed retrospectively.
      Anterior resection was performed in 126, abdominoperineal resection in 48, and
      other surgical procedures in 20 patients. Irradiation was conducted with a single
      daily fraction of 1.8 Gy until 45 Gy, and chemotherapy consisted of the
      combination of 5-fluorouracil and folinic acid (Machover schedule): 47% of
      patients with positive nodes did not receive chemotherapy. RESULTS: Five-year
      overall survival was 60.6% and relapse-free survival was 55.5%. The main
      prognostic factors were pathological T and N stages. The principal route of
      progression was distant metastases. Acute toxicity was severe in 1 case (drug
      toxic hepatitis) and very severe in 16 patients, and late severe sequelae
      appeared in 13 patients. CONCLUSIONS: The outcome of rectal cancer patients has
      not changed during the last decade, and this was confirmed in our study. The
      improvement of radiotherapy techniques has reduced the adverse acute and late
      toxicity. The best postsurgical approach for pT3pN0 cancer remains unsolved, as
      the good chemotherapy combination and the real solution could be the application
      of a new Consensus Conference.

PMID- 15237583
TI  - High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic
      carcinoma: is it useful?
AB  - AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the
      possible improvement in prognosis of patients with prostatic carcinoma undergoing
      radiation therapy with dose escalation or in combination with hormone therapy.
      However, in studies on hormone therapy, moderate doses of radiation therapy have
      been used, whereas in studies with high-dose radiotherapy, hormone therapy
      usually was not administered. Therefore, it is not clear whether the concomitant
      use of high doses and prolonged hormone therapy could determine an additional
      beneficial effect. The aim of the present study was therefore to evaluate the
      relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of
      external beam radiotherapy and of different hormone therapies (neoadjuvant only
      versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71
      yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to
      prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy
      (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months
      before radiotherapy and for its entire duration). Dose to the prostate was < 70
      Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients
      received adjuvant hormonal therapy. The distribution according to the clinical
      stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score
      was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution
      according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0%
      for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a
      median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed
      biochemical recurrence, 17 patients (4.0%) showed local disease progression, and
      12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed
      disease progression. Four patients (0.9%) died. At the time of this writing, no
      patient has died from prostatic carcinoma. At univariate analysis, the radiation
      dose delivered to the tumor and the administration of adjuvant hormone therapy
      were shown to be significantly correlated with biochemical disease-free survival.
      At multivariate analysis, the single parameter significantly correlated with
      biochemical disease-free survival was the radiation dose delivered to the tumor.
      In the subset of patients not treated with adjuvant hormone therapy, there was a
      significant correlation between radiation dose and biochemical disease-free
      survival at univariate and multivariate analysis. A similar correlation between
      adjuvant hormone therapy and biochemical disease-free survival was observed in
      the subset of stage cT3 patients at univariate and multivariate analysis. In
      patients undergoing combined treatment without adjuvant hormone therapy, a
      significant correlation was observed between clinical stage and biochemical
      disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS:
      The results of the study confirmed the positive impact of radiotherapy doses > 70
      Gy and of adjuvant hormone therapy in patients with locally advanced prostatic
      carcinoma. Owing to the lack of evidence of a correlation between radiation dose
      and biochemical outcome in patients undergoing prolonged hormone therapy, the
      role of further dose escalation in patients undergoing combined hormone and
      radiation therapy is still unclear.

PMID- 15237585
TI  - Postoperative radiochemotherapy in rectal cancer comparison of two combination
      schemes: alternating versus concomitant.
AB  - AIMS AND BACKGROUND: To compare the results on disease control and toxicity of
      two different schedules of adjuvant combined treatment in advanced rectal cancer.
      METHODS: From January 1995 to September 1998, 127 patients with stage B2-C rectal
      cancer were treated with postoperative chemotherapy and radiotherapy with two
      different schemes: three cycles of 5-fluorouracil and leucovorin followed by
      pelvic radiotherapy and three weeks after radiation therapy was completed,
      another three cycles of chemotherapy were administered (alternating arm), or two
      cycles of 5-fluorouracil and leucovorin followed by concurrent radiochemotherapy
      and three weeks after ending another two cycles of 5-fluorouracil and leucovorin
      were administered (concomitant arm). RESULTS: Grade 3 acute toxicity was more
      frequent in the concomitant schedule group (33% vs 13%, P = 0.014). In the
      alternating schedule group, the acute adverse effects were observed after an
      average radiation dose of 28.4 Gy and in the concomitant schedule group after an
      average dose of 22.7 Gy (P = 0.012). In the arm of concomitant treatment, 37.8%
      of patients had to interrupt the irradiation for severe toxicity compared to
      10.4% in the arm of alternating treatment (P = 0.001). There was no difference in
      the rate of late toxicity. The actuarial overall survival rates at 3 and 5 years
      were, respectively, 68.8% and 56.6% in the alternating arm and 75.5% and 61.8% in
      the concomitant arm (P = 0.4599). There were no differences between the two arms
      in the 5-year actuarial rates of overall recurrence (47% vs 51.3%, P = 0.722),
      local recurrence (34.6% vs 35.7%, P = 0.935) or distant recurrence (32.7% vs
      31.8%, P = 0.983). CONCLUSIONS: For patients with B2-C rectal cancer,
      postoperative treatment with an alternating scheme of chemoradiotherapy is as
      effective as a concomitant scheme in control of the disease. The concomitant
      scheme had a higher incidence, earlier appearance and higher severity of
      intestinal acute toxicity than the alternating scheme, with a lower completion
      rate of chemoradiotherapy but without any influence on late toxicity incidence.

PMID- 15237586
TI  - Persistent human papilloma virus infection as an indicator of risk of recurrence
      of high-grade cervical intraepithelial neoplasia treated by the loop
      electrosurgical excision procedure.
AB  - OBJECTIVE: To evaluate the recurrence rate of high-grade cervical intraepithelial
      neoplasia (CIN) treated by the loop electrosurgical excision procedure (LEEP)
      according to the persistence of human papilloma virus (HPV) infection. DESIGN:
      Prospective observational study. SETTING: The Florence District screening program
      for cervical cancer. SAMPLE: Eighty-four cases of CIN2/3 consecutively treated by
      LEEP and actively followed up. METHOD: Cases underwent HPV testing (polymerase
      chain reaction) prior to LEEP and after 6 months, and then cyto-colposcopic
      followup every 6 months. MAIN OUTCOMES MEASURES: Recurrence was defined as
      histological evidence of high-grade CIN. The association of recurrence to age and
      CIN grade at treatment and to cytologic and HPV test findings at recurrence was
      determined. RESULTS: The average recurrence rate was 11.9% (10/84 cases; 95% CI,
      5.9-20.8%). Recurrence probability was not significantly associated to age (chi2
      = 0.25, df = 2, P = 0.88) or CIN grade (CIN 3 = 8/57, CIN2 = 2/27, chi2 = 0.26,
      df = 1, P = 0.6), whereas a significant association was evident for the cytology
      report (< LSIL = 6/76, HSIL > or = 4/8, chi2 = 8.55, df = 1, P = 0.003) and HPV
      testing (absent = 1/48, present = 9/36, chi2 = 8.23, df = 1, P= 0.004).
      CONCLUSIONS: Most CIN2 > recurrences after LEEP occur in subjects with persistent
      HPV infection. Subjects with negative findings at cytology, colposcopy and HPV
      testing are at negligible risk of recurrence and might return safely to standard
      screening protocol.

PMID- 15237587
TI  - Outcome of laparoscopic splenectomy for malignant hematologic diseases.
AB  - AIM: The role of laparoscopic splenectomy in the treatment of hematological
      diseases is still controversial. The aim of this study was to assess whether the
      benign or malignant nature of hematological diseases may influence the outcome of
      laparoscopic splenectomy. PATIENTS AND METHODS: Between August 1997 and March
      2002, 63 unselected patients with hematologic diseases underwent a laparoscopic
      splenectomy. Patients were divided into two groups according to the benign (Group
      A, 38 patients) or malignant (Group B, 25 patients) nature of the hematological
      diseases. RESULTS: Patients in group B were significantly (a) older, (b) had
      larger spleens that more frequently needed accessory incisions for specimen
      retrieval, (c) had greater transfusion requirements, and (d) were fed later than
      patients in group A. There were no statistically significant differences among
      the two groups in terms of (a) body-mass index, (b) operative time, (c)
      conversion rate, (d) blood loss, (e) pain medication requirements, and (f)
      hospital stay. Two postoperative deaths occurred among patients in group B, but
      none of them was related to surgery. CONCLUSIONS: The results of the study showed
      that: a) the nature of the disease does not influence the outcome of laparoscopic
      splenectomy, b) the size of the spleen might increase the risk of conversion, but
      it is no longer a contraindication to laparoscopic splenectomy, and c)
      laparoscopic splenectomy can be effectively performed in the treatment of
      malignant hematologic diseases.

PMID- 15237588
TI  - Bcl2 expression and its correlation with neuroendocrine differentiation in colon
      carcinomas.
AB  - AIMS AND BACKGROUND: In this study we investigated the association between BCL2
      expression and neuroendocrine differentiation in tubular adenomas and colon
      carcinomas. We also evaluated the prognostic significance of BCL2 expression and
      neuroendocrine differentiation in the carcinoma group. METHODS: Forty-eight colon
      carcinomas and twelve tubular adenomas were stained immunohistochemically with
      BCL2 and chromogranin A (CgA). Staining patterns were scored semiquantitatively
      and correlated with tumor type, tumor grade, Dukes stage, and survival time.
      RESULTS: BCL2 expression was detected in 7 of 12 (58.3%) adenomas and 37 of 48
      (77.0%) carcinomas. In normal mucosa we observed positive staining only in the
      basal portions of the crypts. However, diffuse positivity was observed in the
      adenomas and carcinomas. Carcinomas had significantly higher BCL2 scores than the
      normal group, but we did not observe any significant differences either between
      the adenoma and carcinoma group or between the adenoma and normal group. BCL2
      scores were higher in stage B than in stage C tumors, and in adenocarcinomas than
      in mucinous carcinomas. CgA positivity was observed in 24 of 48 (50%) carcinomas.
      It was not detected in adenomas. We did not find a significant correlation
      between CgA expression and any of the clinicopathological parameters. CONCLUSION:
      On consecutive sections BCL2 and CgA positivity closely paralleled each other and
      a significant positive correlation was observed between CgA and BCL2 expression.
      These findings suggest a close association between BCL2 expression and
      neuroendocrine differentiation and indicate that BCL2 may be involved in
      neuroendocrine differentiation in addition to its role in protecting cells from
      apoptosis.

PMID- 15237590
TI  - Decrease in length of hospitalization before death of cancer patients in the
      Italian province of Imperia.
AB  - Although the overall cure rates for cancer in Italy are comparable to those of
      other developed countries, these results are the product of very heterogeneous
      facilities. In order to assess the possible impact of improved acute cancer care
      services on the last phase of life, a retrospective study was carried out which
      included 4238 patients registered at the Division of Medical Oncology of Imperia
      Province from January 1995 to December 2002. In 1998 the Province of Imperia,
      with a population of 217,000, had only two doctors and five day-hospital beds.
      During 1999 and 2000, resources increased to include five oncology specialists
      and 10 day-hospital beds. Compared to 1998, in 2002 the number of new patients
      registering at the Division of Medical Oncology and the number of day-hospital
      treatments increased by 76% and 67%, respectively. Since end-of-life care for
      advanced cancer patients is expensive, the length of hospitalization of cancer
      patients dying in acute hospital settings was analyzed for the years 1995-2002.
      Of the 4238 patients registered during the eight-year period, 1433 (33.8%) died
      before 31 December 2002. Among these 1433 patients, the records relative to
      hospitalization and death were available for 571 cancer patients, 324 males
      (56.7%) and 247 females (43.3%) with a median age of 70 years (range, 21-91). The
      average number of days of hospitalization declined from 14.6 (range, 1-76) in
      1998 to 8.2 (range, 1-29) in 2002, a decrease of approximately 44%. The length of
      hospitalization prior to death has declined considerably for cancer patients in
      the Imperia Province and the costs of acute hospital facilities for end-of-life
      care in cancer patients have decreased. In addition, fewer days in hospital
      before death may have had an important impact on the quality of life of these
      cancer patients.

PMID- 15237589
TI  - Low expression of p63 and p73 in osteosarcoma.
AB  - BACKGROUND: The recent discovery of two p53-related genes, p63 and p73, has
      revealed an additional level of complexity to the study of p53 function. Both
      genes encode multiple proteins arising from alternative promoter usage and
      splicing, with transactivation, DNA-binding, and tetramerization domains. Recent
      data support a role for p63 in squamous and transitional cell carcinomas, as well
      as in certain lymphomas and thymomas. METHODS: To characterize the involvement of
      p63 and p73 in the development of osteosarcoma, we analyzed the expression and
      mutation of TAp63 and TAp73 in six osteosarcoma cell lines and twelve
      osteosarcoma specimens. RESULTS: Semiquantitative DNA/PCR analysis revealed that
      eight (67%) and six (50%) out of twelve osteosarcoma specimens showed
      significantly reduced levels of p63 and p73 transcription, respectively. Direct
      sequencing of the entire coding region detected no mutations in cell lines or
      osteosarcoma specimens. CONCLUSIONS: Our data suggest that low expression of p63
      and p73 is relatively common in osteosarcomas and might contribute to their
      molecular pathogenesis.

PMID- 15237591
TI  - Successful pregnancy after vaginal cancer treated with interferon.
AB  - A 25-year-old white woman with a vaginal invasive epidermal carcinoma was treated
      with interferon-alpha 2b (3,000,000 U intralesional, every two days for a total
      of 18 applications). Follow-up with Papanicolaou and colposcopy showed complete
      regression of the vaginal lesion, After three years the patient got pregnant. The
      prenatal course was uneventful and a vaginal delivery was performed. She is
      currently in follow-up without any signs of recurrence.

PMID- 15237592
TI  - An unusual mesenteric paraganglioma producing human chorionic gonadotropin.
AB  - Adrenal and extra-adrenal paragangliomas are uncommon neoplasms arising from the
      parenchymal cells of paraganglia. The presenting symptoms are mostly due to
      excess catecholamine secretion. Extra-adrenal paragangliomas are mostly localized
      in the superior para-aortic region of the abdomen. Mesenteric paragangliomas are
      very rare. We report an unusual case of mesenteric paraganglioma producing human
      chorionic gonadotropin (hCG). To the best of our knowledge, this is the first
      case report describing hCG secretion in an extra-adrenal paraganglioma.

PMID- 15237593
TI  - Inflammatory metastatic carcinoma of the colon: a case report and review of the
      literature.
AB  - Cutaneous metastases from colon cancer are uncommon and usually present as
      nodular lesions. We describe a patient with colonic carcinoma who developed an
      inflammatory pattern of cutaneous metastases. A review of the literature is also
      presented. Recognition of this entity is important as it may be mistaken for
      erysipelas and radiation recall phenomenon. Early treatment with chemotherapy can
      result in meaningful palliation.

PMID- 15237594
TI  - Paclitaxel-carboplatin induced radiation recall colitis.
AB  - Some chemotherapeutic agents can "recall" the irradiated volumes by skin or
      pulmonary reactions in cancer patients who previously received radiation therapy.
      We report a recall colitis following the administration of paclitaxel-containing
      regimen in a patient who had been irradiated for a carcinoma of the uterine
      cervix. A 63-year-old woman underwent a Wertheim operation because of uterine
      cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and
      she received curative external radiotherapy (45 Gy) to the pelvis. No significant
      adverse events were observed during the radiotherapy. Approximately one year
      later, she was hospitalized because of metastatic disease with multiple pulmonary
      nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was
      administered. The day after the administration of chemotherapy the patient had
      diarrhea and rectal bleeding. Histological examination of the biopsy taken from
      rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared
      after the administration of each course of chemotherapy and continued until the
      death of the patient despite the interruption of the chemotherapy. In conclusion,
      the probability of recall phenomena should be kept in mind in patients who
      received previously with pelvic radiotherapy and treated later with cytotoxic
      chemotherapy.

PMID- 15237595
TI  - Pylethrombosis associated with gastric cancer in Moschcowitz's disease:
      successful management with anticoagulant. Report of a case.
AB  - Portal vein thrombosis secondary to gastric cancer has been rarely reported. The
      main difficulty is represented by the correct differential diagnosis between
      benign and malignant thrombus and therefore by its treatment. In this report we
      describe a 62-year-old woman with Moschcowitz's disease who developed
      pylethrombosis and gastric cancer. Preoperative examination confirmed the
      relationship between the portal vein thrombosis and Moschcowitz's disease. She
      underwent an aggressive surgical procedure for the gastric cancer and
      conservative treatment of the thrombosis with subcutaneus administration of 8000
      IU/day of low molecular weight heparin (LMWH) at the time of diagnosis,
      interrupted eight hours before surgery and resumed eight hours after with 4000
      IU/day. At discharge LMWH treatment was replaced with oral sodium warfarin home
      treatment to keep the international normalized ratio range between 2 and 3.
      Regression of the thrombosis with low molecular weight heparin was confirmed by
      computed tomography. The patient survived more than two years. We believe that
      patients with gastric cancer complicated by benign partial portal vein thrombosis
      could gain particular benefit from adjuvant anticoagulant treatment, so that the
      surgical approach can be limited to gastric cancer.

PMID- 15237596
TI  - Mesenteric vein thrombosis after surgery and radiotherapy for pancreatic
      carcinoma. A case report.
AB  - A case is reported of a 54-year-old female patient undergoing the resection of a
      pancreatic carcinoma with intraoperative radiation therapy (10 Gy) on the tumor
      bed and subsequent external beam radiotherapy (50 Gy). After surgery the patient
      presented chronic diarrhea resistant to oral pancreatic enzymes. Twenty-five
      months postoperatively, mesenteric vein thrombosis was diagnosed after an episode
      of melena and was treated with conservative therapy. At five-year follow-up the
      patient had no evidence of neoplastic disease and bowel movements had increased.
      On imaging examinations, the presence of venous collaterals and cavernous
      appearance of the portal trunk were documented.

PMID- 15237598
TI  - [The AIOM (Italian Association of Medical Oncology) practice guidelines for
      breast neoplasms].

PMID- 15237597
TI  - Recurrent intracranial hemangiopericytoma with extracranial and unusual multiple
      metastases: case report and review of the literature.
AB  - Hemangiopericytoma is a rare tumor with uncommon location in the central nervous
      system. It has only recently been included (WHO classification 1993) in a
      specific group of CNS tumors and subsequently (WHO classification 1997 and 2000)
      as a group by itself, while before it was confused with meningeal tumors. We
      report on a case of a 48-year-old woman affected by this tumor. The neoplasm was
      located in the posterior fossa. The patient underwent primary surgery in 1990,
      not followed by any adjuvant therapy because of the histopathological diagnosis
      of meningioma. After being free from disease for eight years she developed a
      local recurrence in 1998. Subtotal excision of the tumor, which was finally
      identified as a hemangiopericytoma, was carried out, followed by adjuvant
      radiotherapy (64 Gy). After six months multiple metastases were found in the
      liver and right kidney. A radical metastasectomy was performed, followed by
      systemic chemotherapy. One year later (2001) the tumor recurred again
      intracranially and a metastases was detected in the right breast, so the patient
      again underwent cranial irradiation (40 Gy) and second-line chemotherapy. She
      died in September 2002, 12 years after the diagnosis. We may conclude that,
      despite the tumor's natural tendency to recur several times and the ability of
      intracranial hemangiopericytoma to spread outside the CNS, it is possible to
      ensure a long survival time.

PMID- 15237599
TI  - [Ibandronate: keep life in motion].

PMID- 15237600
TI  - The physiology of taste and smell: how and why we sense flavors.
AB  - Taste and smell work together to identify the chemical composition of what we
      intend to ingest. In recent years, our understanding of the mammalian physiology
      of taste and smell has greatly increased. In addition to its intrinsic value,
      this increased understanding of the molecular and cellular basis of flavor
      recognition provides also a new view on our behavioral response to edible matter.

PMID- 15237601
TI  - The olfactory experience: constants and cultural variables.
AB  - Odor and olfaction anthropology explores four lines of research which, in many
      cases, may overlap: the variability of the olfactory perception, olfactory skills
      and know-how, odor use, and odor representations. My proposal here is to deal
      with the first one, trying to answer the following question: is olfactory
      perception a phenomenon resulting solely from the biological organization of the
      human being, in such a way that it does not know other variations than the ones
      due to nature? Or, on the contrary, can we show different kinds of olfaction
      culturally determined or, at least, environmental influences resulting in
      significant perceptual differences among groups, societies, cultures, etc.? In
      the first part of the text, I will deal with the invariants (or universals). In
      the second, I will insist on the cultural types of olfaction. In the third and
      last part, I will advance the following proposal: beyond the discussion on the
      roles that nature and culture play in human olfaction, we can sustain that
      naturally and culturally, there is a way of smelling characteristic of our
      species. Finally, I will conclude with two examples of the symbolic treatment
      characteristic of the olfactory human experience.

PMID- 15237602
TI  - A guide to geosmin- and MIB-producing cyanobacteria in the United States.
AB  - A guide to confirmed geosmin- and MIB-producing cyanobacteria isolated in the
      United States is being prepared. This document will include 41 different species
      or morphologically distinct types from eight states and diverse aquatic sources
      isolated over a 22-year period. The organisms comprised by this guide demonstrate
      the importance of attached cyanobacteria as off-flavor agents, the strain
      specificity of MIB production, the existence of unicellular MIB producers, the
      occurrence of multiple geosmin and MIB producers in reservoirs, and the
      relationship of certain planktonic odor producers to species in other countries.

PMID- 15237603
TI  - Nuisance odours produced by benthic cyanobacteria in a Mediterranean river.
AB  - Geosmin dynamics in the Llobregat waters were related to the waxing and waning of
      benthic cyanobacterial mats developing in the river. Geosmin concentration in the
      water during 2002 reached a maximum of 204 ng L(-1), and coincided with an
      abundance of cyanobacteria in the river. Cyanobacterial mats were favoured by the
      high nutrient content of the waters. The cyanobacterial mats experienced a
      process of growth in thickness (attached forms), until they became unattached and
      drifted downstream (free-floating forms), accumulating in shallow areas of the
      river. Geosmin in the biofilm ranged from 0.55 +/- 0.97 ng geosmin per mg DW(-1)
      in the attached biofilms and 5.25 +/- 4.96 ng geosmin per mg DW(-1) in the free
      floating biofilms. While the attached mats could be responsible for the local
      occurrence of geosmin at a given site, the free-floating mats became a relevant
      agent for the dispersion of the metabolite downstream. This impression was
      reinforced by the extremely high correlation between the geosmin content in the
      free-floating biofilm and in the water (r = 0.917, p = 0.00001). In order to
      reduce the geosmin concentration and accumulation of the cyanobacterial mats in
      shallow river waters, the nutrient content should be controlled and the natural
      flow conditions restored, to prevent the growth and accumulation of the geosmin
      producing cyanobacterial mats.

PMID- 15237604
TI  - Periphyton: a primary source of widespread and severe taste and odour.
AB  - In the last decade, a late summer-fall taste and odour problem has been a
      prolonged and annual event in the St Lawrence River (SLR). Earlier work
      identified the earthy/musty compounds geosmin and particularly, 2
      methylisoborneol (GM-MIB), and ruled out Lake Ontario as a major source, but did
      not identify the biological origins. In 2000, we investigated the source(s) and
      underlying causes. We sampled littoral sites in the SLR near Cornwall, ON, and
      found that macrophytes (or associated biofilms) may be primary GM sources. Zebra
      mussel homogenate yielded low GM-MIB levels, but several associated actinomycetes
      generated high in vitro amounts. Periphyton from rocks showed significant yields,
      with cell-bound GM-MIB up to one hundred times the levels in overlying water. In
      2001, we followed seasonal changes at some of these sites. Periphyton GM-MIB
      showed intriguing spatial and temporal patterns. Several cyanobacteria in these
      biofilms were identified as potential odour sources, notably Oscillatoriales. We
      conclude: i) periphyton is a major odour source in the SLR; ii) other biota such
      as macrophytes and mussels may also contribute; iii) seasonality in GM-MIB
      production and ratios indicate changes in cell production and/or taxa in response
      to environment. These results may account for the recent onset of the problematic
      odour events, which represent chemical signals of the increased water
      transparency and littoral surface area following the widespread dreissenid mussel
      invasion to the Great Lakes. Our data raise key questions about the processes
      that trigger the tremendous variability in biota and GM-MIB production in the
      SLR, the subject of our continued research.

PMID- 15237605
TI  - Species specificity of musty odor producing Phormidium tenue in Lake Kamafusa.
AB  - 16S ribosomal DNA sequences of various strains of Phormidium tenue (P. tenue) in
      Lake Kamafusa were determined. Such P. tenue could not be distinguished under
      microscopic examination. From the results of the analyses of base sequences, and
      using a phylogenetic tree, several P. tenue with different species specificity on
      the sequence were found in the lake. P. tenue were divided into three groups. The
      first produced 2-methylisoborneol (MIB) and was close to a species from the moat
      of Nagoya castle. The second produced MIB and was characteristic of Lake
      Kamafusa. The third had a brown color like a Lake Biwa strain and was MIB non
      producing. From the phylogenetic tree, it was revealed that species had not
      changed recently by mutation. Moreover, a detection method for P. tenue by PCR
      and dot hybridization was established.

PMID- 15237606
TI  - Volatile organic compound (VOC) analysis and sources of limonene, cyclohexanone
      and straight chain aldehydes in axenic cultures of Calothrix and Plectonema.
AB  - The volatile organic compounds (VOCs) in four standing cultures of axenic benthic
      cyanobacteria (Calothrix and Plectonema) were studied by GC/MS analysis. To
      verify the biogenic origin of the VOCs, 13C-labelling experiments were performed,
      and the differences in labelling were used to differentiate between biogenic and
      non-biogenic sources. Strongly labelled biogenic compounds were derived from the
      shikimate (cresol, skatole), isoprenoid (beta-cyclocitral, beta-ionone, geosmin)
      and fatty acid pathways (5Z-heptadecene, 3-octanone, 1-hexanol). New odour
      compounds derived from microorgansims were beta-cyclogeraniol, dihydro-beta
      ionone and 2-hydroxy-2,6,6-trimethylcyclohexanone. The latter compound had
      already been found in lake water, but could not be assigned to a particular
      organism. Straight chain aldehydes (octanal, nonanal, decanal), cyclohexanone,
      cyclohexanol and limonene were unlabelled beyond their natural isotope ratio.
      Therefore, the biogenic origin of these compounds is doubtful despite their
      occurrence in axenic cultures. The observation that limonene was a racemate
      supports this view. The precursors and reactions that lead to the formation of
      these non-biogenic compounds are unknown and it may be that they are formed by
      the analytical procedures rather than then being present in the culture medium.

PMID- 15237607
TI  - Rating method for evaluating distribution-system odors compared with a control.
AB  - A new sensory method was developed and tested at a full-scale water treatment
      plant. The method evaluates changes in aesthetic water quality during transit in
      the distribution system. A paired comparison format is used to determine if the
      odor of a distribution-system sample is different from that of a control sample.
      The control sample represents the "ideal" water, such as treated water leaving
      the plant. The method can rapidly determine whether or not a problem exists in
      the distribution system, and, if one does exist, it allows for characterization
      of the problem. Over a three-month period a 4-member odor panel evaluated 118
      distribution samples by this new procedure. Among the 118 samples tested, 39
      samples yielded a consensus among the analysts as to the odor characteristics of
      the sample; 35 were rated "not different from the control" (about 90%), and only
      4 were rated "different from control" (about 10%). The 79 samples for which no
      consensus was generated had only slight rating differences between analysts and
      for odor intensity. No taste-and-odor problems were reported by consumers during
      the time period for this study and the method indicated that no major odor
      problems existed in the distribution system.

PMID- 15237608
TI  - The attribute rating test for sensory analysis.
AB  - This new sensory method evaluates the intensity of an odorant by using a modified
      "paired-comparison" format. It can be applied to any situation for which the odor
      causing agent is known and a purified standard is available. The attribute rating
      test requires that a standard solution of the odorant be prepared at a
      concentration that is both readily recognized by most individuals and likely to
      evoke customer complaints. Within an hour individuals can be trained to compare
      the odor type and intensity of the standard to water samples, then rate the odor
      in the sample as "not detected," "less than the standard," "equal to standard,"
      or "greater than the standard." The attribute rating test was successfully used
      by a full-scale water treatment facility to monitor the intensity of geosmin in
      the source water and to determine the effectiveness of powdered activated carbon
      for controlling its earthy-odor in treated water.

PMID- 15237609
TI  - Taste and odour testing: how valuable is training?
AB  - Correct identification of specific tastes and odours in a water supply can be a
      powerful tool in identifying the cause of the problem and facilitating rapid
      remediation. While taste and odour identification can be achieved by laboratory
      testing, consumer involvement is not only worthwhile as a public education
      exercise but can also indicate tastes and odours to which the public do not
      object. Interpretation of taste and odour results is a complex process. The
      Australian Water Quality Centre (AWQC), based in Adelaide, South Australia, has
      established a flavour profile panel, trained in Flavour Profile Analysis (FPA).
      This group was chosen to carry out a survey of tastes and odours present in
      selected Australian water supplies and laboratory treated water and bottled
      water. The waters were also assessed by a group of untrained volunteers to
      simulate the responses of consumers. In two series of tests there were
      significant differences in responses between the groups with respect to the
      intensity of the tastes and odours detected. In both instances the responses by
      the trained group were more consistent, making interpretation of results more
      straightforward. In the second series of tests the panellists were also asked
      their personal preferences. The results showed in general the preferred waters
      were those with minimal taste and odour and this was generally irrespective of
      the type of taste and odour present.

PMID- 15237610
TI  - Utility quick test for analyzing materials for drinking water distribution
      systems for effect on taste-and-odor.
AB  - A workshop of international drinking water experts was convened in Sedona,
      Arizona, March 26-27, 2001 for the purpose of developing a method for testing
      drinking water system components for their potential to contribute to taste-and
      odor problems in drinking water. The workshop participants derived a method using
      provisions from European Standards as well as newly developed approaches. It is
      intended that this method can serve as a temporary procedure for water utilities,
      as well as a recommended template to derive an official standard. Materials to be
      tested may include pipes, fittings, ancillaries, joints, lubricants, tanks, and
      reservoirs. The recommended method includes a migration (leaching) test with
      chlorinated water, followed by sensory analysis of the samples from the migration
      test after dechlorination. Sensory analyses use both statistical (e.g., triangle
      test) and descriptive (e.g. Flavor Profile Analysis) techniques. A decision tree
      for the results is provided.

PMID- 15237611
TI  - Design and application of a GC-SNIff/MS system for solving taste and odour
      episodes in drinking water.
AB  - This paper describes the implementation of a GC-Sniff/MS system that allows the
      simultaneous determination of the odorous properties of compounds eluting from a
      GC column and their identification by MS. The technique was first tested with
      standard compounds then applied to real cases of taste and odour episodes. This
      approach allowed the identification of geosmin at low levels and suggested the
      possible implication of methylnaphthalene in the development of chemical odours.
      It provided the first clue of the presence of a halophenol with a very low odour
      threshold involved in a chlorophenolic odour episode. The chemical was finally
      identified as 2,6-dibromophenol. The method was also applied to the
      characterization of a complex mixture of additives leaching from a flexible
      rubber pipe. In the latter case, Time-of-Flight MS was also used to confirm the
      identity of the additives.

PMID- 15237612
TI  - Use of headspace solid-phase microextraction to characterize odour compounds in
      subsurface flow constructed wetland for wastewater treatment.
AB  - A headspace solid-phase microextraction (HS-SPME) preconcentration method was
      applied to the analysis of some of the major odorous compounds occurring in
      wastewater using GC/MS or GC/NPD detection. The detection limit for volatile
      amines, volatile fatty acids, and volatile alkylsulphides ranged from 3 to 100, 2
      to 150, and 0.0006 to 0.035 microg/L, respectively. The SPME method was used to
      examine the fate of odorous compounds in the subsurface flow constructed wetlands
      (SFCW) operated under different hydraulic loading rate (HLR), bed aspect ratio,
      and granular medium size. Among the experimental conditions evaluated in the SFCW
      beds, HLR was found to be the most important factor influencing the evolution of
      the studied compounds. There were also significant differences among bed types in
      the behaviour of ammonia (NH3), acetic acid (Ac), isovaleric acid (IsoA),
      propionic acid (PrA), and dimethylsulphide. Aspect ratio and medium granular size
      were minor factors influencing SFCW performance. The major odour compounds by
      mass in the effluent of SFCW with different operational conditions were NH3 and
      Ac. Further removal of these two compounds is considered as very important from
      the viewpoint of chemical composition. On the other hand, Relative Odour
      Intensity (ROI: ratio between the absolute concentration to the odour threshold
      concentration) suggested that PrA and IsoA were the two major compounds
      responsible for odour intensity. Thus, further removal of these two compounds is
      viewed as very important for the effluent deodorization, especially for PrA. From
      our results, this compound appears to be produced by processes occurring in the
      SFCW.

PMID- 15237613
TI  - Chlorophenols identification in water using an electronic nose and ANNs
      (artificial neural networks) classification.
AB  - Electronic artificial noses are being developed as systems for the automated
      detection and classification of odours, vapors and gases. In the food industry,
      such devices are used as aids for quality control or process-monitoring tools. An
      electronic nose (EN) is generally composed of a chemical sensing system and a
      pattern recognition system (e.g. artificial neural network). An EN based on a non
      specific conducting polymer array was used to monitor chlorophenols in water
      samples. Operational parameters for the EN were optimized by a Plackett-Burman
      factorial design. The experimental parameters studied were: sample volume, platen
      temperature, sample equilibration time, loop fill time, sample pressurization
      time and injection time. Optimal experimental conditions were applied to
      chlorophenols determination and differentiation in ultrapure water samples spiked
      with the EPA listed chlorophenols. Data analysis was carried out using principal
      component analysis (PCA) and artificial neural networks (ANNs) to predict the
      chlorophenols presence in water samples. The obtained results showed that it was
      possible to differentiate the five chlorophenol groups: monochlorophenol,
      dichlorophenol, trichlorophenol, tetrachlorophenol and pentachlorophenol.
      Differentiation of chlorophenol groups was based on Mahalanobis distance between
      the formed clusters. This Mahalanobis distance is designated by the Quality
      Factor, a value >2 for this quality factor means a good differentiation between
      the clusters.

PMID- 15237614
TI  - Statistical comparison of the triangle test and the two-of-five test for taste
      and odor evaluation.
AB  - The Triangle test and 2-of-5 test are compared for their ability to evaluate
      tastes and odors in water and wastewater utilities. Both tests have varying
      statistical sensitivities. The 2-of-5 test is more sensitive and more powerful
      than the Triangle test, and generally requires fewer panelists for the same level
      of statistical confidence. This paper presents a method for determining the
      number of panelists for either test, and compares the results.

PMID- 15237615
TI  - Synthesis and odour thresholds of mixed halogenated anisoles in water.
AB  - Earthy-musty off-flavour compounds in water samples are usually associated with
      the presence of geosmin and 2-methylisoborneol. However, the presence of 2,3,6-
      and 2,4,6-trichloroanisoles or other halogenated anisoles can impart
      objectionable tastes and odours to the water even at very low trace levels. This
      paper shows the synthesis of non-commercial 2,3,6- and 2,4,6- mixed
      chloro/bromoanisoles which can be present in bromide rich waters and could also
      be suspected of imparting earthy-musty off-flavours to the water. All the
      synthesized compounds were subjected to the flavour profile analysis (FPA) method
      and their odour threshold concentrations (OTC) in water were carried out giving
      values in the low ng/L range.

PMID- 15237616
TI  - An analytical method for shipboard extraction of the odour compounds, 2
      methylisoborneol and geosmin.
AB  - Extractions for the analysis of geosmin and 2-methylisoborneol (MIB) were carried
      out on board a research vessel by extracting water samples in the collection
      bottles with dichloromethane. The extracts are stable and can be stored for up to
      two months with no apparent loss of analytes. Workup and analysis could be done
      at the rate 15-20 samples per week. Approximately 150 samples from Lake Ontario
      were analyzed in 2000 and 120 samples in 2001. Concentrations as low as 1 ng/L
      could be detected, but reliable determination was only attained above 5 ng/L (>
      80% qualifier ion match within +/- 50%). Reproducibility between duplicates was
      generally better than 10%, and recovery of surrogate standards from reagent water
      averaged ca. 80% and from lake water ca. 60%. In early September, 2000, geosmin
      concentrations in Lake Ontario ranged from 1-13 ng/L and MIB from 1-31 ng/L. In
      2001, the ranges were 1-47 and 1-56 ng/L for geosmin and MIB, respectively.
      Lowest concentrations occurred in the western and central regions and highest
      concentrations in the eastern region and St Lawrence River.

PMID- 15237617
TI  - Taste and odor profiles (off-flavors) in the drinking waters of the Barcelona
      area (1996-2000).
AB  - The Aigues de Barcelona laboratory systematically monitors the organoleptic
      quality of the water it supplies. The water comes mainly from the Llobregat and
      Ter rivers, with the two sources having cleary differentiated chemical
      characteristics. Water is monitored by the tasting panel, which works according
      to FPA (Flavor Profile Analysis) principles. This paper reports the results from
      the period 1996-2000: characteristic organoleptic profiles, evolution of
      descriptors and the overall organoleptic evaluation of the water. The results
      show that in Llobregat water the descriptors chlorinous, medicinal, rubbery and
      salty are the most relevant, whereas in Ter water fresh nature/grassy and
      metallic are. The Aesthetic Quality Index drawn up by our laboratory confirms
      that Ter water has better organoleptic quality than Llobregat water. Monitoring
      also found that neither water lost quality significantly within the distribution
      network.

PMID- 15237618
TI  - Non-specific monitoring to resolve intermittent pollutant problems associated
      with wastewater treatment and potable supply.
AB  - An online monitoring system based on an array of non-specific sensors was used
      for the detection of chemical pollutants in wastewater and water. By
      superimposing sensor profiles for defined sampling window, the identification of
      data points outside these normal sensor response patterns was used to represent
      potential pollution episodes or other abnormalities within the process stream.
      Principle component analysis supported the detection of outliers or rapid changes
      in the sensor responses as an indicator of chemical pollutants. A model based on
      the comparison of sensor relative responses to a moving average for a defined
      sample window was tested for detecting and identifying sudden changes in the
      online data over a 6-month period. These results show the technical advantages of
      using a non-specific based monitoring system that can respond to a range of
      chemical species, due to broad selectivity of the sensor compositions. The
      findings demonstrate how this non-invasive technique could be further developed
      to provide early warning systems for application at the inlet of wastewater
      treatment plants.

PMID- 15237619
TI  - The panel of Aigues de Barcelona: 15 years of history.
AB  - The Aigues de Barcelona Laboratory has been working on odour and taste research
      in water for 15 years. During the entire period its basic tool has been the FPA
      (Flavour Profile Analysis) standard method, used by a group of trained tasters.
      This paper reports the main activities of the panel in recent years, such as the
      recruitment and training of panellists, the wheel of descriptors used, the
      Aesthetic Quality Index (AQI) developed for the quality control of water
      supplies, various research studies, and taste and odour episodes in which it has
      helped.

PMID- 15237620
TI  - Effects of chlorine and chloramines on earthy and musty odors in drinking water.
AB  - Water treatment plants in the US may operate under the assumption that chlorine
      masks earthy and musty odors from geosmin and 2-methylisoborneol (MIB) in
      drinking water. To test this hypothesis, we evaluated the effects of chlorine and
      chloramines on geosmin and MIB by two sensory analysis approaches--a statistical
      Pairwise Comparison Test, and Flavor Profile Analysis (FPA). All Pairwise Ranking
      test statistics were significant (p<0.05); we conclude that panelists can
      differentiate minor differences in geosmin and MIB concentrations in a Pairwise
      Comparison Test even in the presence of chlorine. FPA appeared to be more
      challenging in discerning subtle differences in concentrations of geosmin or MIB
      than did the Pairwise Comparison Test, and the presence of chlorine (0.5-20 mg/L)
      and chloramines (3-24 mg/L) confused the panelists (i.e showed a larger error in
      the intensity of response reported by the panel), but did not necessarily mask
      geosmin or MIB.

PMID- 15237621
TI  - Optimization of stir bar sorptive extraction applied to the determination of
      odorous compounds in drinking water.
AB  - The off-flavour compounds 2-methylisoborneol (MIB), geosmin, 2,4,6
      trichloroanisole, 2,3,6-trichloroanisole, 2,3,4-trichloroanisole and 2,4,6
      tribromoanisole were analyzed in water samples by Stir Bar Sorptive Extraction
      (SBSE) followed by on-line thermal desorption (TD)-capillary GC/MS.
      Quantification was performed using MS in the single ion monitoring mode (SIM)
      with 2,4,6-trichloroanisol-D5 as internal standard. Quantification limits are 0.1
      ng/l to 0.2 ng/l for the haloanisoles, 0.5 ng/l for geosmin and 1 ng/l for MIB.
      The relative standard deviations at the quantification limit are ranging from 7
      to 14.6%. SBSE-recovery was evaluated by spiking real water samples and varied
      from 87 to 117%. More than twenty samples per day can be analyzed by SBSE-TD
      capillary GC-MS. The same technique in combination with olfactometry was used to
      elucidate unknown odorous compounds in water samples.

PMID- 15237622
TI  - Compost odor control using high carbon wood ash.
AB  - A pilot study on the feasibility of using high carbon wood ash to control
      composting odor emissions was conducted at a green material composting facility.
      The study's treatments consisted of adding 0%, 12.5%, and 25% high carbon wood
      ash by volume to green-material compost feedstock in three separate windrows. The
      wood ash has properties similar to activated carbon with an active surface area
      of 105 square metres per gram on a dry weight basis. The odorant emission data
      suggest that the higher percentage wood ash treatment results in the most
      effective control of most compost odors and that wood ash provides effective
      treatment of volatile fatty acids and some aldehydes and ketones. The 25% wood
      ash treatment resulted in more effective treatment of odors for a longer time
      period than the 12.5% treatment. Acetaldehyde had the highest concentration in
      the control (14,000 times its odor threshold concentration), was reduced by high
      carbon ash by over 97% but remained 386 times its reported odor threshold
      concentration after 14 days. Ethyl mecaptan and ammonia were produced in the
      process and were also over their reported human detection limits.

PMID- 15237623
TI  - Inorganic polysulfides' quantitation by methyl iodide derivatization:
      dimethylpolysulfide formation potential.
AB  - Inorganic polysulfides are important intermediates in the formation of
      dimethylpolysulfides and possibly other volatile sulfur compounds of
      environmental significance. Currently, direct determination of these ions in the
      concentration range of natural systems is practically impossible, particularly
      under oxic conditions. Polysulfide quantification by derivatization with methyl
      iodide or d6-methyl iodide is emerging as a valuable alternative method for
      studies of polysulfide formation in natural systems. This manuscript presents
      detailed studies aimed at the evaluation of this method. We determined the
      conversion of the inorganic polysulfides to dimethylpolysulfides by methylation
      with methyl iodide. Close to 100 per cent of the molar concentration of
      polysulfide salts were converted to organic polysulfides for very low
      concentrations of dissolved polysulfide solutions, but only a small recovery was
      obtained for high concentrations of polysulfide precursors or when the solubility
      limit was exceeded. The recovery of polysulfides based on the calculated
      dissolved polysulfide concentration exceeds 1,000 per cent for very low dissolved
      concentrations of polysulfides. This unexpected dependence is attributed to
      continuous inorganic polysulfide formation from hydrogen sulfide and sulfur
      precipitate concurrent with, and in fact driven by, the methylation process.

PMID- 15237624
TI  - The odour of digested sewage sludge--determination and its abatement by air
      stripping.
AB  - This paper describes a project to investigate the odour of sewage sludge after
      anaerobic digestion. The impact of air stripping on the odour of liquid sludge
      and on the quality of the dewatered product was evaluated at a full-scale sludge
      treatment installation. A continuous and a batch air-stripping mode were tested.
      Odour samples were collected during air stripping from the liquid sludge and from
      the biosolids surface during long term storage. The biosolids were also analysed
      for hedonic tone and for their potential odour expressed as an odour unit per
      unit mass. The odour emission profiles for continuous and batch air stripping
      demonstrated a reduction in the overall (time weighted) emissions during a 24 hr
      period compared with emissions from the quiescent liquid storage tank. The
      averaged specific odour emission rate (Esp) of the biosolids derived from the
      continuous process was only 13% of the Esp of the biosolids derived from
      unaerated liquid sludge during the first month of storage. The results of the
      total potential odour and the hedonic tone of the biosolids underpin the
      beneficial effects of the air stripping. Odour dispersion modelling showed a
      noticeable reduction in overall odour impact from the sludge centre when air
      stripping was applied. The reduction was primarily associated with the reduced
      odour from stockpiled biosolids. The continuous air-stripping mode appeared to
      provide the greatest benefits in terms of odour impact from site operations.

PMID- 15237625
TI  - Understanding odorants associated with compost, biomass facilities, and the land
      application of biosolids.
AB  - Odorous water and air can result from compost, biomass facilities and land
      application of biosolids. Common odorous compounds from these biodegradation
      systems include alcohols, aldehydes, fatty acids, solvents and various sulfur and
      nitrogen compounds. Each odorant possesses a unique individual odor signature
      i.e. odor character or quality, odor threshold concentration and chemical
      concentration. This paper develops an initial understanding of how the volatile
      odorous chemicals and their relative concentrations produced are related to the
      total odor quality from the process by their odor threshold concentrations. The
      compost process is used as an example. It was estimated, that on day 1 and 7, the
      primary fatty acids controlling the fermented and rotten odors were butyric acid
      and valeric acids, individually, unpleasant and rancid odors, respectively,
      although acetic acid had the highest fatty acid concentration on both days. In
      the same way, aldehydes and ketones controlled the disappearance of the sweet
      odor from day 1 to 7.

PMID- 15237626
TI  - Development of an odor wheel classification scheme for wastewater.
AB  - Overall, in the air pollution control field, odor concentration and intensity as
      well as hedonic rating have been well studied to the point where some level of
      standardization is being developed or is already in place. However, there has
      been no standardization with respect to odor quality characterization. There is
      now sufficient understanding of the types of odorous compounds that can arise
      from wastewater treatment processes to develop an odor classification scheme.
      This article presents the first wastewater odor wheel or classification scheme
      that should form the foundation for the evolution of odor quality data reporting
      with links to chemical causes.

PMID- 15237627
TI  - Biofilm in water pipelines; a potential source for off-flavours in the drinking
      water.
AB  - Volatile organic compounds (VOC) are identified in natural biofilm established in
      plastic pipes used at the drinking water supply. Odour potent VOCs such as
      ectocarpene, dictyopterene A and C', geosmin, beta-ionone, 6-methyl-5-hepten-2
      one, menthol and menthone were prominent compounds in biofilm in the distribution
      network and at raw water test sites, and are associated with algae and
      cyanobacteria present in the raw water source.

PMID- 15237628
TI  - Materials used in drinking water distribution systems: contribution to taste-and
      odor.
AB  - In order to assist drinking water utilities with identifying the possible sources
      and causes of taste-and-odor conditions associated with materials used in
      distribution systems, we evaluated information from case studies and a database
      from the National Sanitation Foundation (NSF), International. This database
      identified chemicals that had leached from drinking water system components
      during testing of materials under ANSI/NSF Standard 61, which provides
      information to water utilities on potential taste-and-odor and health concerns
      from the use of new materials. The data were arranged to provide a process for
      locating the potential source of a taste-and-odor event. After a sensory analysis
      is conducted on the drinking water samples, the descriptor can be matched with
      categories on the "Drinking Water Taste and Odor Wheel 2000" in order to suggest
      the candidate material.

PMID- 15237629
TI  - Tastes associated with products in contact with drinking water.
AB  - Over the past 9 years the Australian Water Quality Centre (AWQC) has conducted
      testing in accordance with Australian and New Zealand Standard AS/NZS 4020-
      "Products for use in contact with drinking water" (1999). A test included as part
      of this standard is taste of water extracts. This test assesses the ability of
      products to impart discernible taste to drinking water using panellists trained
      in accordance with Standard Methods for the Examination of Water and Wastewater-
      Flavour Profile Analysis 2170 B (1999). Over 1000 products from companies
      worldwide, have been assessed at the AWQC in accordance with AS/NZS 4020
      including pipes, valves, tap fittings and numerous other products used in contact
      with water. The products must not impart any discernible taste to obtain
      compliance and be deemed suitable for use in contact with drinking water. This
      study compiles the products assessed and the types of tastes obtained from both
      chlorinated and non-chlorinated extracts. In particular the study focuses on
      taste associated with polyethylene pipes, coatings and valves, which in some
      instances have been problematic. Analysis revealed that most taste problems occur
      when chlorinated water has been used in extraction experiments and this is in
      line with consumer complaints regarding taste imparted by plumbing products. The
      collation of this data provides a valuable assessment for manufacturers, the
      water industry and consumers.

PMID- 15237630
TI  - The effect of applying a pipe-joint lubricant to connect ductile iron pipe on off
      flavors in drinking water distribution systems.
AB  - This study was used to help define the contribution to taste and odor problems
      caused by the application of a pipe-joint lubricant to connect ductile iron pipe
      in drinking water distribution systems. Tyton Joint Lubricant (TJL) was studied.
      The lubricant produced odors that are continually oxidized by chlorine or oxygen.
      The mechanism of oxidative rancidity, one of the major causes of food spoilage is
      the apparent mechanism of oxidation. The odors produced by the lubricant were
      characterized by a Flavor Profile Analysis (FPA) panel as well as GC/MS and
      Sensory GC analysis. The most common odors perceived in the TJL water samples for
      the first six days were waxy/oily and soapy odors with a rancid oil, odor note.
      The waxy/oily and soapy odors decreased with time in the chlorine medium as the
      rancid oily odor note increased. Numerous aldehydes, ketones, alcohols and
      borneol compounds, produced from the lubricants, were tentatively identified and
      linked to the odors perceived by the FPA panel.

PMID- 15237631
TI  - Sensory evaluation of the odors produced during bromophenol formation using a
      multi-level statistical model.
AB  - In response to reports of medicinal taste and odor problems in suburban Paris, a
      lab scale study was conducted to investigate the contribution of different water
      quality parameters--pH, phenol, bromide, chlorine, temperature and dissolved
      oxygen levels--on bromophenol medicinal odor formation using the Flavor Profile
      Analysis (FPA) method. A study of six parameters at 2 levels (64 experiments)
      analyzed by the FPA method suggests that chlorine at high concentration is more
      important as a controlling agent than phenol under similar conditions and the
      ratio of HOBr:Phenol and the time for reaction will control subsequent brominated
      products of reaction. Results from a three-level statistical model indicate that
      high pH was associated with lower odor intensities, whereas high levels of
      chlorine, phenol and temperature were associated with high odor intensities.
      Potential worst case scenarios of water quality conditions were determined for
      evaluation by chemical identification and kinetics.

PMID- 15237632
TI  - The effect of water quality and NOM character on the ozonation of MIB and
      geosmin.
AB  - The ozonation of MIB and geosmin was studied in synthetic waters containing two
      natural organic material (NOM) fractions and sodium bicarbonate. The ozonation of
      both compounds was found to be affected by the character of the NOM fractions,
      with higher apparent rate constants observed in the fraction containing higher
      UV/visible absorbing properties. As the concentration of bicarbonate was
      increased, the destruction of both compounds decreased. MIB was found to be more
      resistant to ozonation than geosmin.

PMID- 15237633
TI  - NOM and MIB, who wins in the competition for activated carbon adsorption sites?
AB  - The adsorption of an odour compound common in drinking water, 2-methylisoborneol
      (MIB), was studied on two activated carbons in the presence of 13 well
      characterised natural organic matter (NOM) solutions. It was found that, although
      the carbons and the NOM solutions had a wide range of characteristics, the major
      competitive mechanism was the same in all cases. The low molecular weight NOM
      compounds were the most competitive, participating in a direct competition with
      the MIB molecule for adsorption sites. Equivalent background concentration (EBC)
      calculations indicated a relatively low concentration of directly competing
      compounds in the NOM. Some evidence of pore restriction was also seen, with
      microporous carbons most affected by low molecular weight NOM, and mesoporous
      carbons impacted by the higher molecular weight compounds.

PMID- 15237634
TI  - Determination of odour threshold concentrations and dose-response relations in
      water of several minor disinfection by-products: aldehydes and alkyl nitriles.
AB  - The odour threshold concentrations (OTCs) levels of aldehydes and alkyl nitriles,
      two groups of disinfection by-products of water treatment, have been studied in
      order to know if some of these compounds can be associated with off-flavour
      events. For aldehydes, as a result of the values obtained, which are in the low
      microg/L range, it is possible that they are related to these events. This is not
      the case for the other group, alkyl nitriles, with very high OTC values.

PMID- 15237635
TI  - Removal of geosmin and 2-methylisoborneol by biological filtration.
AB  - The quality of drinking water is sometimes diminished by the presence of certain
      compounds that can impart particular tastes or odours. One of the most common and
      problematic types of taste and odour is the earthy/musty odour produced by
      geosmin (trans-1, 10-dimethyl-trans-9-decalol) and MIB (2-methylisoborneol).
      Taste and odour treatment processes including powdered activated carbon, and
      oxidation using chlorine, chloramines, potassium permanganate, and sometimes even
      ozone are largely ineffective for reducing these compounds to below their odour
      threshold concentration levels. Ozonation followed by biological filtration,
      however, has the potential to provide effective treatment. Ozone provides partial
      removal of geosmin and MIB but also creates other compounds more amenable to
      biodegradation and potentially undesirable biological instability. Subsequent
      biofiltration can remove residual geosmin and MIB in addition to removing these
      other biodegradable compounds. Bench scale experiments were conducted using two
      parallel filter columns containing fresh and exhausted granular activated carbon
      (GAC) media and sand. Source water consisted of dechlorinated tap water to which
      geosmin and MIB were added, as well as, a cocktail of easily biodegradable
      organic matter (i.e. typical ozonation by-products) in order to simulate water
      that had been subjected to ozonation prior to filtration. Using fresh GAC, total
      removals of geosmin ranged from 76 to 100% and total MIB removals ranged from 47%
      to 100%. The exhausted GAC initially removed less geosmin and MIB but removals
      increased over time. Overall the results of these experiments are encouraging for
      the use of biofiltration following ozonation as a means of geosmin and MIB
      removal. These results provide important information with respect to the role
      biofilters play during their startup phase in the reduction of these particular
      compounds. In addition, the results demonstrate the potential biofilters have in
      responding to transient geosmin and MIB episodes.

PMID- 15237637
TI  - Treatment of taste and odor material by oxidation and adsorption.
AB  - Massive blooms of blue-green algae in reservoirs produce the musty-earthy taste
      and odor, which are caused by compounds such as 2-MIB and geosmin. 2-MIB and
      geosmin are rarely removed by conventional water treatment. Their presence in the
      drinking water, even at low levels (ng/L), can be detected and it creates
      consumer complaints. So those concentrations have to be controlled as low as
      possible in the drinking water. The removals by oxidation (O3, Cl2, ClO2) and
      adsorption (PAC, filter/adsorber) were studied at laboratory and pilot plant (50
      m3/d) to select suitable 2-MIB and geosmin treatment processes. The following
      conclusions were derived from the study. Both of the threshold odor levels for 2
      MIB and geosmin appeared to be 30 ng/L as a consequence of a lab test. For any
      given PAC dosage in a jar-test, removal efficiencies of 2-MIB and geosmin were
      increased in proportion to PAC dosage and were independent of their initial
      concentration in raw water for the tested PAC dosages. In comparison of geosmin
      with 2-MIB, the adsorption efficiency of geosmin by PAC was superior to that of 2
      MIB. The required PAC dosages to control below the threshold odor level were 30
      mg/L for geosmin and 50 mg/L for 2-MIB at 100 ng/L of initial concentration.
      Removal efficiencies of odor materials by Cl2, ClO2, and O3 were very weak under
      the limited dosage (1.5 mg/L), however increased ozone dosage (3.8 mg O3/L)
      showed high removal efficiency (84.8% for 2-MIB) at contact time 6.4 minutes.
      According to the initial concentrations of 2-MIB and geosmin, their removal
      efficiencies by filter/adsorber differed from 25.7% to 88.4%. For all those,
      however, remaining concentrations of target materials in finished waters were
      maintained below 30 ng/L. The longer run-time given for the filter/adsorber, the
      higher the effluent concentration generated. So it is necessary that the run-time
      of the filter/adsorber be decreased, when 2-MIB or geosmin occurs in raw water.

PMID- 15237636
TI  - The effect of oxidants on 2-MIB concentration with the presence of cyanobacteria.
AB  - In this study, the effect of three oxidants, sodium hypochlorite, potassium
      permanganate, and ozone, were tested for the removal of 2-MIB with presence of
      cyanobacteria. Algae in water samples from the source water of Feng-Shen
      waterworks (FSW), Taiwan were cultivated at 30 degrees C with continuous light at
      an intensity between 2,500 and 3,400 lux. During the cultivating process, water
      samples were analyzed for nutrients, light absorbance at 665 nm (A665), and 2-MIB
      concentration. The 2-MIB concentrations within the incubated samples increased to
      as high as 1,000 ng/L to 2,000 ng/L, although no extra nutrients were added to
      the raw water. After 2 to 3 days incubation, the intracellular 2-MIB
      concentration was as high as 70% of the total 2-MIB in the samples. The algae
      that developed were mainly cyanobateria, and more than 90% belonged to the Genus
      Oscillatorias. An almost 100% removal of both 2-MIB and geosmin in the raw water
      was observed after ozonation for 10 minutes at a dosing rate of 0.91 mg/l-min.
      Chlorine and permanganate were much less effective, both removing only about 11%
      of the 2-MIB within 60 minutes at oxidant concentration of 10 mg/l. Oxidation of
      the cultivated samples showed that chlorine and permanganate may damage algae
      cells causing them to release intracellular 2-MIB. During the 60 minutes of
      reaction time, the total 2-MIB concentrations (intracellular plus dissolved)
      varied by no more than 10%, however, the ratios between dissolved and total 2-MIB
      concentrations increased. Two effects of ozonation on the 2-MIB concentration in
      the cultivated samples were observed when the algae were young, namely 2-MIB
      release from damaged cells and 2-MIB oxidization. The rates of 2-MIB release and
      2-MIB destruction were similar. However, old algae cells were more easily
      damaged. As a result, intracellular 2-MIB was released faster, and the soluble 2
      MIB was destroyed more quickly by ozonation.

PMID- 15237638
TI  - Role of oxidants and disinfectants on the removal, masking and generation of
      tastes and odours.
AB  - This paper summarises the positive and negative effects of the most commonly used
      oxidants and disinfectants: chlorine, chloramines, chlorine dioxide, potassium
      permanganate ozone, and advanced oxidation with ozone/hydrogen peroxide on tastes
      and odours present in natural and drinking waters. The case studies reported
      illustrate the generation of odorous by-products such as chlorophenols,
      iodoforms, aldehydes, the masking effect between earthy-musty and chlorinous
      odours, and the removal of odorous algal metabolites or anthropogenic pollutants
      by ozone alone or by ozone coupled with hydrogen peroxide.

PMID- 15237639
TI  - Geosmin occurrence in riverine cyanobacterial mats: is it causing a significant
      health hazard?
AB  - Toxicity endpoints (nonspecific cytotoxicity, hepatotoxicity, neurotoxicity,
      immunotoxicity, and mutagenicity) were studied in cyanobacterial mats obtained
      from a shallow river. Some of the cyanobacterial mats tested were known to be non
      geosmin producers, while others were geosmin-producers. No microcystin-like
      compounds were detected by HPLC in any of the biofilm samples. The mutagenicity
      and neurotoxicity of biofilm metabolites was negligible, and generally weak
      adverse effects of biofilm extracts detected in a battery of in-vitro assays
      indicated relatively low human health risks associated with biofilm toxicity.
      While the toxicity responses detected in the studied biofilms were weak, effects
      were not related to production of geosmin. It was therefore concluded that the
      production of this metabolite cannot be taken as an indication per se of the
      existence of a health hazard.

PMID- 15237640
TI  - Effect of blending two treated waters on the organoleptic profile of Barcelona's
      supply.
AB  - Barcelona's drinking water has two distinct origins: the Ter and Llobregat rivers
      supply the city in a ratio of 35/65. The organoleptic quality of the two waters
      is very different. Treated water from the Llobregat sometimes has organoleptic
      problems, whereas the quality of treated water from the Ter is much better. The
      aim of this paper is to study the effects of blending the two types of water and
      to determine the best blend of the Ter and Llobregat treated waters in terms of
      flavour and odour, using the A/not A test and the Flavour Profile Analysis. The
      optimum blend of Ter and Llobregat water is the blend that contains the highest
      percentage of Llobregat water without any appreciable loss of the characteristics
      of Ter water.

PMID- 15237641
TI  - Chlorinous flavor perception in drinking water.
AB  - Chlorinous flavors at the tap are the leading cause of customers' complaints and
      dissatisfaction with drinking water. To characterize consumer perception and
      acceptance to chlorinous tastes, extensive taste testing was performed with both
      trained panelists and average consumers. Taste testing with trained panelists
      showed that chlorine perception is underestimated by disinfectant flavor
      thresholds reported in the literature. However, trained panelists significantly
      overestimate the average consumer's ability to perceive chlorine. In addition,
      consumer perception seems to be influenced by the chlorination practices of the
      country they live in. Among water quality characteristics that may influence
      chlorine perception, temperature was not found to induce any significant change.
      The influence of total dissolved solids (TDS) on chlorine perception remains
      unclear and, as reported elsewhere, background tastes such as musty, may
      significantly impact chlorine threshold.

PMID- 15237642
TI  - Determination of nanogram level of VSCs using GC-SCD and an adsorption tube.
AB  - A quantitative analytical method was used for detection of low level of volatile
      sulfur compounds (VSCs) using GC with a sulfur chemiluminescence detector (SCD)
      in this study. A linear response over the range of 2-90 ngS injected was obtained
      with a good repeatability or reproducibility. Equimolar response for H2S, DMS,
      MeSH, and EtSH was obtained by use of SCD and the response of the SCD is nearly
      equimolar for different sulfur compounds. It was possible to quantify the total
      VSCs as well as individual VSC using one of the standard VSCs. VSC recovery was
      measured with respect to some storing methods. An adsorption tube packed with
      molecular sieve 5A showed almost perfect recovery for both H2S and dimethyl
      sulfide (DMS) during 6 days at a dark state below 2 degrees. Whereas, with a gas
      tight pyrex vial or tedlar bag, it was impossible to obtain the recovery of 50%
      after 6 days. It is strongly recommended to use the adsorption tube for
      determination of nanogram levels of volatile sulfur compounds and for storing and
      concentrating VSCs effectively with a minimum experimental error.

PMID- 15237644
TI  - It's a small world, after all.

PMID- 15237643
TI  - Public thresholds for chlorinous flavors in U.S. tap water.
AB  - Considering this rapid growth in the purchasing of bottled water and home
      filtration devices, utilities are increasingly concerned about consumer
      dissatisfaction with tap water quality. This project aimed to characterize public
      perceptions of chlorinous flavors in drinking water, and how these impact
      customers' choices with respect to consumption of tap water alternatives. On-site
      taste tests at seven water utilities with 30 to 40 panelists at each site, were
      conducted using a forced-choice triangle test method (ASTM method E679-91) to
      measure public sensitivity to chlorine and chloramine in drinking water. The
      chlor(am)ine concentration increased from set to set. The best-estimate
      sensitivity limit for each panelist was the geometric mean of that concentration
      at which the last miss occurred and the next (adjacent) higher concentration. The
      measured sensitivity limit of average American populations to free chlorine (159
      persons tested) and chloramine (93 persons tested) in tap water were 0.8 and 3.7
      mg/L Cl2, respectively. These thresholds are much higher than those previously
      reported in the literature using trained FPA panels. No significant differences
      were observed between tap water users and users of tap water alternatives or
      between the various markets tested with respect to average sensitivity, though
      individual sensitivity varied widely.

PMID- 15237645
TI  - Strengthening the profession through mentoring 2004.

PMID- 15237647
TI  - The paraoptometric professional.

PMID- 15237646
TI  - The globalization of optometry: challenges and opportunities in the new
      millennium--part I.

PMID- 15237648
TI  - State of the profession: 2004.

PMID- 15237649
TI  - Human resource management: a systems-based approach.

PMID- 15237650
TI  - Medicare to require proper ZIP codes, phone numbers, ICD-9s on all electronic
      claims.

PMID- 15237651
TI  - Why albumin may still work.

PMID- 15237652
TI  - Malaria and money.

PMID- 15237653
TI  - [Extravasation of cytotoxic agents].
AB  - A variety of antineoplastic agents is associated with toxicity to healthy tissue
      and therefore represents a hazard for patients in case of extravasation. The most
      common risk factors include patient associated and iatrogenic risk factors. Due
      to the possible complications after extravasation, the knowledge of these risk
      factors is the basis for prevention, which is of utmost importance. A
      classification of antineoplastic agents according to the type of tissue damage
      includes the categories vesicant, irritant, and non-vesicant. Dependent on the
      extravasated agent, a series of emergency measures should be considered,
      preferably adhering to a standard operation procedure. There is good evidence for
      the successful use of antidotes to some antineoplastic agents. These antidotes
      are dimethylsulfoxide or hyaluronidase, often combined with topical measures such
      as cooling or application of heat. The application of sodium bicarbonate, sodium
      thiosulfate, and heparin is not recommended, whereas the usefulness of
      corticosteroids is still a matter of controversial discussions. Ambiguity in the
      management of extravasation is often a consequence of limited clinical evidence.
      Due to our deficient knowledge about some of the administered cytotoxics, there
      is ongoing need for action even after decades of therapy with antineoplastic
      agents.

PMID- 15237654
TI  - [Treatment of achalasia].
AB  - Achalasia is a condition of unknown etiology. It represents a motor disorder of
      the esophagus characterized by absent or incomplete relaxation of the lower
      esophageal sphincter upon swallowing and by non-propulsive swallow-induced
      contraction waves or amotility of the esophageal body. Dysphagia and
      regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e.
      by calcium-channel blockers and nitric oxide donors, may be tried in patients
      with mild dysphagia or in elderly patients but rarely yields adequate symptom
      relief. Mechanical dilatation of the achalasic sphincter may be performed as an
      initial treatment option. Intrasphincteric injections of botulinum toxin seemed
      to be a promising alternative, but it has become obvious that, in most cases,
      repeated applications of the toxin are required to maintain patients symptom
      free. Myotomy of the achalasic sphincter with or without fundoplication to
      prevent gastroesophageal reflux, is employed mainly in patients in whom
      dilatations have failed, but since the introduction of minimally invasive
      surgery, myotomy has become the primary treatment at many centers. This article
      aims to provide an overview of the development of the conservative and surgical
      treatment of achalasia.

PMID- 15237655
TI  - Human albumin and starch administration in critically ill patients: a prospective
      randomized clinical trial.
AB  - OBJECTIVE: To determine whether intravenous infusion of either human albumin or
      hydroxyethyl-starch (HES) in hypo-albuminemic critically ill may lead to an
      increase in colloid osmotic pressure and to a better clinical outcome, i.e. lower
      mortality and fewer complications, compared to fluid replacement with normal
      saline. DESIGN: Prospective, randomized controlled clinical trial during 72 hours
      in 61 consecutively admitted severely ill patients. Randomisation took place by
      sealed envelope, kept outside of the hospital. SETTING: Intensive care unit of
      the Twenteborg Hospital, Almelo, The Netherlands. SUBJECTS: Sixty-three severely
      ill, hypo-albuminemic patients were selected; 27 patients had severe sepsis and
      36 were post-surgical patients with SIRS. Two patients died shortly after
      randomization, 15 patients received human albumin, 15 HES 500 and 15 HES 1000 ml,
      and 16 saline. INTERVENTIONS: The patients were randomized to receive 300 ml
      human albumin (20%) per day, or 1000 ml normal saline per day, or 500 ml or 1000
      ml HES per day, all for 72 hours. MAIN OUTCOME MEASURES: The primary outcome was
      plasma colloid osmotic pressure (COP). Secondary endpoints were fluid balance and
      the development of pulmonary edema. RESULTS: Administration of human albumin was
      effective in raising COP (P<0.001 on day 2 and day 3, compared to saline and
      HES). Neither fluid balances nor the development of peripheral or pulmonary edema
      were different between the groups. Mortality as well as length of stay at ICU
      were slightly higher in the group receiving human albumin, although not
      statistically significant. CONCLUSION: Raising colloid osmotic pressure with
      human albumin in hypoalbuminemic patients is not associated with improvement of
      the clinical outcome.

PMID- 15237656
TI  - High-dosage continuous amiodarone therapy to treat new-onset supraventricular
      tachyarrhythmias in surgical intensive care patients: an observational study.
AB  - BACKGROUND: New-onset supraventricular tachyarrhythmias (SVTA) are a complication
      contributing significantly to morbidity and mortality in surgical intensive care
      unit (SICU) patients. Although only few data on efficiency can be found in the
      literature, class III antiarrhythmics have become popular in the treatment of
      SVTA in critically ill patients. SETTING: 12-bed general and surgical ICU in a
      university teaching hospital. DESIGN: Observational, retrospective study.
      PATIENTS: 131 SICU patients with SVTA (narrow-complex non-sinus tachyarrhythmias
      with heart rates > or = 100 bpm). INTERVENTION: High-dosage amiodarone infusion
      according to an institutional protocol. MEASUREMENTS: Hemodynamic data, acid-base
      status, and single organ functions were obtained in all patients before
      amiodarone infusion and at 12, 24, and 48 hours afterwards. Patients were divided
      into responders and nonresponders. Amiodarone infusion (mean dosage 24 h: 1625+/
      528 mg; 48 h: 2708+/-895 mg) restored sinus rhythm in 54% of study patients
      within 12 h, in 64% within 24 h, and in 75% within 48 h. Heart rate, central
      venous pressure, and milrinone requirements significantly decreased in all
      patients; this was accompanied by a significant increase in stroke-volume index
      and mean arterial pressure. Serum concentrations of creatinine and bilirubin
      increased in all patients. CONCLUSION: High-dosage continuous amiodarone infusion
      during a period of 48 hours resulted in restoration of SR in 75% of SICU patients
      with new-onset SVTA and moderate to severe multiple-organ dysfunction syndrome. A
      significant improvement in cardiocirculatory function was more pronounced in
      responders but could be demonstrated irrespective of restoration of sinus rhythm
      in all patients. Apart from a possibly amiodarone-mediated increase in
      concentrations of creatinine and bilirubin, no major drug-related adverse effects
      occurred during the observation period.

PMID- 15237657
TI  - Cystic fibrosis and lung transplantation--determination of the survival benefit.
AB  - INTRODUCTION: Cystic fibrosis is a well acknowledged indication for lung
      transplantation; however, the optimal timing for transplantation remains
      debatable. Liou et al. described a score for calculating 5-year probability of
      survival for patients with cystic fibrosis and concluded that only patients with
      a probability of survival < 30% gained a survival benefit from transplantation;
      those between 30% and 50% had equivocal survival effects from transplantation and
      those > 50% suffered negative effects. The aim of the present study was to
      determine the validity and applicability of this model. METHODS: Data from
      patients with cystic fibrosis transplanted between January 1995 and July 2001
      were retrospectively reviewed. Survival score according to Liou was calculated
      from data collected before transplantation. Patients were classified according to
      5-year probability of survival (group 1: < 30%, group 2: 30%-50%, groups 3-5: >
      50%). Actuarial survival rates were calculated separately for each group and
      compared with the predicted probability of survival. RESULTS: During the
      observation period 27 patients were transplanted for cystic fibrosis. Three
      patients had to be excluded from further analysis because of incomplete
      pretransplant data. Fifteen patients were classified as group 1 and nine patients
      as group 2. No patients were eligible for groups 3 to 5. There were nine female
      patients and six males in group 1, mean age 22.1 +/- 4.9 years. Mean survival
      time was 918 +/- 787 days; 1-, 3- and 5-year survival rates were 66.6%. Three
      male patients and six females were classified as group 2, mean age 26.2 +/- 12.2
      years. Mean survival time for this group was 701 +/- 617 days, and 1-, 3- and 5
      year survival rates were 66.6%. CONCLUSION: We found that only patients with a 5
      year probability of survival < 50% had been transplanted. For patients in groups
      1 and 2 we report identical 5-year survival rates of 66.6%. According to our
      experience, cystic fibrosis patients with a 5-year probability of survival < 30%
      and also those between 30% and 50% gain a clear survival benefit from bilateral
      lung transplantation.

PMID- 15237658
TI  - An 8-year experience in airborne contact dermatitis.
AB  - OBJECTIVE: A large number of case reports concerning occupational airborne
      contact dermatitis have been published in the last few years. Our purpose was to
      establish the prevalence of airborne contact dermatitis in a routinely patch
      tested population and to obtain further epidemiologic data. METHODS: In a single
      center study, the data of 5,092 routinely patch-tested patients were collected
      using a standardized questionnaire and a documentation form. The study period
      extended from October 1994 to March 2002. RESULTS: The clinical diagnosis was
      airborne contact dermatitis in 15 cases (0.29%). Patch testing revealed positive
      and relevant results in nine patients (0.18%). Plant or wood extracts were the
      sensitizers in all cases but two, and perfume and epoxy resin were the
      sensitizers in one case each. The diagnosis of an irritant airborne contact
      dermatitis was established in six patients. A relationship with occupation was
      found in seven cases (0.14%) when 'housewife' was included as an occupational
      category and in five cases (0.1%) when this was excluded. CONCLUSION: Airborne
      contact dermatitis is a rare diagnosis in an unselected patch-test population. An
      occupational relationship was less common than has been implied in case reports
      in recent years.

PMID- 15237659
TI  - Monitoring mixed venous oxygen saturation in patients with obstructive shock
      after massive pulmonary embolism.
AB  - BACKGROUND: Patients with massive pulmonary embolism and obstructive shock
      usually require hemodynamic stabilization and thrombolysis. Little is known about
      the optimal and proper use of volume infusion and vasoactive drugs, or about the
      titration of thrombolytic agents in patients with relative contraindication for
      such treatment. The aim of the study was to find the most rapidly changing
      hemodynamic variable to monitor and optimize the treatment of patients with
      obstructive shock following massive pulmonary embolism. PATIENTS AND METHODS: Ten
      consecutive patients hospitalized in the medical intensive care unit in the
      community General Hospital with obstructive shock following massive pulmonary
      embolism were included in the prospective observational study. Heart rate,
      systolic arterial pressure, central venous pressure, mean pulmonary-artery
      pressure, cardiac index, total pulmonary vascular-resistance index, mixed venous
      oxygen saturation, and urine output were measured on admission and at 1, 2, 3, 4,
      8, 12, and 16 hours. Patients were treated with urokinase through the distal port
      of a pulmonary-artery catheter. RESULTS: At 1 hour, mixed venous oxygen
      saturation, systolic arterial pressure and cardiac index were higher than their
      admission values (31+/-10 vs. 49+/-12%, p<0.0001; 86+/-12 vs. 105+/-17 mmHg,
      p<0.01; 1.5+/-0.4 vs. 1.9+/-0.7 L/min/m2, p<0.05; respectively), whereas heart
      rate, central venous pressure, mean pulmonary-artery pressure and urine output
      remained unchanged. Total pulmonary vascular-resistance index was lower than at
      admission (29+/-10 vs. 21+/-12 mmHg/L/min/m2, p<0.05). The relative change of
      mixed venous oxygen saturation at hour 1 was higher than the relative changes of
      all other studied variables (p<0.05). Serum lactate on admission and at 12 hours
      correlated to mixed venous oxygen saturation (r=-0.855, p<0.001). CONCLUSION: In
      obstructive shock after massive pulmonary embolism, mixed venous oxygen
      saturation changes more rapidly than other standard hemodynamic variables.

PMID- 15237660
TI  - Impact of increasing consultation fees on malaria in Africa.
AB  - To evaluate the impact of the increase in consultation fees on malaria incidence
      in children presenting in the outpatient clinic of a privately funded hospital,
      we measured the impact of two fee increases on the number of pediatric
      outpatients. A 74% reduction in outpatients and a 78% reduction in malaria cases
      occurred in a course of four years. No differences were observed in an adjacent
      public hospital that does not charge consultation fees. This surprisingly strong
      effect may be the basis for increase in malaria morbidity and mortality, since in
      the time course of 4 years, an estimated 3000 children did not receive adequate
      malaria treatment in this region. Furthermore, it may drive parasite resistance,
      due to inadequate auto-medication.

PMID- 15237661
TI  - Refractory Wegener's granulomatosis responds to tumor necrosis factor blockade.
AB  - Wegener's granulomatosis is a systemic necrotising vasculitis of small vessels
      that leads to severe impairment of affected organ systems. Conventional treatment
      is based on immunosuppression with a combination of steroids, cyclophosphamide,
      azathioprine or methotrexate over a prolonged time course. Early recurrence or
      disease refractory to therapy often results in a fatal outcome. As in other
      inflammatory disorders, tumor necrosis factor (TNF) plays an early and crucial
      role in progression of disease activity. We report on a patient with severe
      orbital Wegener's granulomatosis who developed acute renal failure despite
      intense conventional immunosuppression with cyclophosphamide and steroids. To
      stop vasculitic activity, by disrupting the autoimmune inflammatory cascade, a
      TNF-blocking antibody (Infliximab) was administered six times in a six-month
      period at 3 mg/kg body weight. Conventional immunosuppressive therapy with
      steroids and cyclophosphamide was continued, the latter being changed to
      azathioprine after three months. The first infusion of TNF antibody induced
      improvement of renal function, which continued throughout the course of therapy.
      The modification of diet in renal disease-glomerular filtration rate (MDRD-GFR)
      increased from 15.3 ml/min/1.73 m2 before the start of TNF-blockade to 55.5
      ml/min/1.73 m2 after six months of therapy. Serum creatinine levels, proteinuria
      and cANCA titer decreased concomitantly. Clinical remission of Wegener's
      granulomatosis was induced without any major adverse events. A slight flare of
      orbital inflammation was successfully treated with an increased dose of
      azathioprine. Thus, in this case of refractory Wegener's granulomatosis TNF
      blockade by monoclonal chimeric TNF-antibody (Infliximab) served as an effective
      tool to rescue kidney function and induce clinical remission.

PMID- 15237662
TI  - [Austrian Society of Lung Diseases and Tuberculosis: consensus on diagnosis and
      therapy of bronchial asthma in adults].

PMID- 15237663
TI  - The pursuit of excellence.

PMID- 15237664
TI  - Long-term survival after repair of atrioventricular septal defect.

PMID- 15237665
TI  - The Edgar Mannheimer Lecture. Improving the care of patients with congenital
      heart disease: an adult focus.

PMID- 15237666
TI  - A ten year review of atrioventricular septal defects.
AB  - OBJECTIVES: To review all cases of atrioventricular septal defects in Northern
      Ireland from January 1990 to February 1999, examining clinical and morphological
      features, management, and outcome. METHODS: A retrospective case note analysis of
      106 subjects with comparisons between subgroups. RESULTS: An atrioventricular
      septal defect was part of a more complex abnormality in 50 of the patients (47%).
      Down's syndrome was present in 57 (54%). Cardiac surgery was performed in 81%.
      The defects were unrestrictive in 69 patients (65%), 45 of whom had Down's
      syndrome. Complex associated abnormalities existed in 36 patients, and 10 of
      these died without cardiac surgery. Operative mortality was 9.5% for those with
      co-existing Down's syndrome group, and 14.3% for the chromosomally normal
      patients. The ventricular components of the septal defect were restrictive in 23
      patients (22%), with 9 having Down's syndrome. Spontaneous closure occurred in
      more than half of these patients. Mortality was zero. The septal defect was
      exclusively at atrial level in 14 patients ("primum" defects--13%), and 3 of
      these had Down's syndrome. Operative mortality was again zero. Median duration of
      postoperative follow-up was 3 and a half years. Overall, moderate to severe left
      atrioventricular valvar regurgitation was observed postoperatively in 23% at
      follow-up. CONCLUSIONS: Mortality was highest in the atrioventricular septal
      defects with an unrestrictive ventricular component. Uncomplicated cases had good
      outcomes. Patients without Down's syndrome tended to have more associated cardiac
      abnormalities, and to have more postoperative arrhythmias. Approximately half of
      the defects with restrictive ventricular components closed spontaneously.
      Moderate postoperative left atrioventricular valvar regurgitation was commonest
      in patients with the defect exclusively at atrial level.

PMID- 15237667
TI  - Long-term survival in children with atrioventricular septal defect and common
      atrioventricular valvar orifice in Sweden.
AB  - BACKGROUND: The survival for patients with atrioventricular septal defect has
      improved markedly over the last decades and, during the same period, the survival
      of children with Down's syndrome has also increased. The aim of our study was to
      investigate long-term survival in patients having atrioventricular septal defect
      with common valvar orifice, but without associated significant congenital heart
      defects, in the setting of Down's syndrome, comparing the findings to those in
      chromosomally normal children with the same malformation. METHODS AND RESULTS: In
      a population-based retrospective study, we scrutinised the medical records from
      801 liveborn children with atrioventricular septal defect born in Sweden during
      the period 1973 through 1997. Data on gender, presence or absence of Down's
      syndrome, associated congenital heart defects, date of birth, operation and death
      were recorded and followed up until 2001. An isolated atrioventricular septal
      defect with common atrioventricular valvar orifice was present in 502 children,
      of whom 86% had Down's syndrome. We found a significant reduc tion over time in
      age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using
      a multiple logistic regression model, we found no significant differences in
      mortality between genders, nor between those with or without Down's syndrome.
      Early corrective surgery could not be identified as a significant independent
      factor for survival. The 5-year postoperative survival in patients with Down's
      syndrome increased from 65% over the period from 1973 through 1977, to about 90%
      in the period 1993 through 1997, and the same trend was observed in chromosomally
      normal patients. CONCLUSIONS: Survival in uncomplicated atrioventricular septal
      defect with common atrioventricular valvar orifice has greatly increased, and
      surgical correction is now equally successful in patients with Down's syndrome
      and chromosomally normal patients, and for both genders. Death in connection with
      surgery is no longer the major threat, and focus must now be on long-term follow
      up.

PMID- 15237668
TI  - Outcome following, and impact of, prenatal identification of the candidates for
      the Norwood procedure.
AB  - OBJECTIVES: Our study evaluates hospital survival following prenatal
      identification of candidates for the Norwood procedure, and the impact of
      prenatal diagnosis on survival, preoperative stability, and postoperative
      morbidity. METHODS: We reviewed records of all patients who were identified
      prenatally as candidates for the Norwood procedure, and compared them to all
      postnatally diagnosed patients who underwent the Norwood procedure between August
      1995 and May 2002. RESULTS: Of the 98 patients studied, 45 (46%) were diagnosed
      prenatally. Of these, 35 underwent the Norwood procedure, 29 (83%) of who
      survived. Thus, 29 of 45 (64%) patients survived from prenatal diagnosis to
      discharge following the Norwood procedure. Of the 53 postnatally diagnosed
      patients who underwent the Norwood procedure, 42 (79%) survived. Prenatal
      diagnosis was not associated with improvement in survival, preoperative
      stability, or postoperative morbidity. By multivariate analysis, ascending aortic
      diameter equal to or greater than 2 mm (p = 0.01), and gestational age 36 weeks
      or greater (p = 0.01) independently predicted survival. Based on this, patients
      were stratified into groups at low risk, consisting of 69 patients, and at high
      risk, consisting of 19 patients. Prenatal diagnosis was unassociated with
      improved survival in either group. Results were unchanged when the analysis was
      restricted to patients with hypoplasia of the left heart. CONCLUSION: From the
      time of prenatal diagnosis, 64% of patients survived to discharge following the
      Norwood procedure. Prenatal diagnosis did not affect preoperative stability,
      survival or postoperative morbidity. This remained the case after stratifying
      patients by risk, or restricting analysis to patients with hypoplasia of the left
      heart. Ascending aortic diameter and gestational age independently predicted
      survival.

PMID- 15237669
TI  - Repair of aortic coarctation using temporary ascending to descending aortic
      bypass in children with poor collateral circulation.
AB  - Aortic coarctation can now be repaired surgically with excellent results. Even
      though rare, injury to the spinal cord resulting in paraplegia remains a major
      concern. Preoperative evaluation showing the absence of collateral circulation is
      valuable in order to introduce protective actions. This report describes our
      experience using a temporary bypass from the ascending to the descending aorta
      bypass in children undergoing surgical correction of aortic coarctation in the
      setting of poorly developed collateral circulation. Between 1990 and 2002, we
      undertook direct surgical repair in 56 patients with isolated aortic coarctation,
      20 as neonates, 11 as infants, and 25 during childhood. From 1998 onwards, we
      introduced preoperative evaluation of the collateral circulation with magnetic
      resonance imaging. From that time, we placed a temporary bypass from the
      ascending to the descending aorta, using a polytetrafluoroethylene tube of 4 to 8
      mm diameter, whenever distal pressures were shown to be 25 mmHg or less after
      test clamping, or when magnetic resonance imaging revealed absence of collateral
      circulation. We found excellent correlations between the direct intra-operative
      measurements of distal pressure and the findings at magnetic resonance imaging.
      Following introduction of the temporary bypass, we observed no neurological
      complications, nor were there any complications related to bypass. Freedom from
      restenosis was 96%. Preoperative magnetic resonance imaging, therefore, can
      accurately visualize poor collateral circulation in children with aortic
      coarctation. The use of a temporary bypass can possibly eliminate the risk of
      neurological sequels following direct repair of coarctation in children with
      poorly developed collateral circulation. The temporary bypass is both easy to
      apply and safe.

PMID- 15237670
TI  - Positional cyanosis in infants: an unusual presentation of right-sided cardiac
      masses.
AB  - Positional cyanosis is an uncommon finding in young patients. We report three
      infants who presented with positional cyanosis due to a pedunculated tumour in
      the right heart. Arterial desaturation was the result of right-to-left shunting
      at the level of the oval foramen caused by obstruction and/or insufficiency of
      the tricuspid valve. The obstruction at the level of the tricuspid valve was
      variable because of the pedunculated nature of the tumours, which gave them
      considerable mobility. Hence, the degree of right-to-left shunting was dependent
      on the position of the patient. In all the patients, surgical resection of the
      tumours resolved the cyanosis.

PMID- 15237671
TI  - Use of covered Cheatham-Platinum stents in aortic coarctation and recoarctation.
AB  - We inserted covered Cheatham-Platinum stents in 4 patients, ranging in age from
      12 to 19 years, who weighed between 45 and 94 kg. All the patients had aortic
      coarctation, with surgical repair having been attempted previously in one, and
      with balloon dilation having been performed as the primary treatment in two,
      resulting in formation of aneurysms. The fourth patient had not received any
      treatment. The gradients were reduced from 10 to 40 mmHg before insertion of the
      stent to 0 to 5 mmHg after stenting. No complications were encountered. All the
      patients are well at an interval of 3 to 14 months after stenting.

PMID- 15237672
TI  - The clinical profile of Ebstein's malformation as seen from the fetus to the
      adult in 52 patients.
AB  - Ebstein's malformation of the tricuspid valve is a rare but complex congenital
      cardiac lesion characterised by a variable degree of dysplasia and displacement
      of the proximal attachments of its inferior and septal leaflets from the true
      atrioventricular junction. The aim of our retrospective study is to report the
      risk factors for mortality, and to determine the clinical profile as seen in 52
      cases diagnosed in our service between 1978 and 2002, concentrating in particular
      on the outcome for the neonatal patient. There were 26 females and 26 males, and
      the age at presentation ranged from 30 weeks gestational age to 46 years. We
      found 23 associated cardiac anomalies in 20 cases. Of the patients, 11 patients
      (21%) died. Actuarial survival at 30 years was 65%. Predictors of death included
      fetal or neonatal presentation, presence of associated defects, a grade within
      the Celermajer index of 3 or 4, and a cardiothoracic ratio equal to or greater
      than 65%. The diagnosis was made in the neonatal period in 24 patients, nine of
      whom died. Of the 15 survivors, only 4 are free of symptoms. Surgical treatment
      was undertaken in 9 patients, with a mortality rate of 33% without late deaths,
      with all the survivors being in good condition. The mean period of follow-up for
      the 41 living patients was 16.5 years. An arrhythmia of variable severity
      appeared during the evolution of 27 patients (66%). At present, only 7 cases are
      in the functional class III or IV of the grading system of the New York Heart
      Association, but 25 patients (61%) needed some medical treatment, meanly for
      arrhythmic events. Thus, fetal and neonatal presentation of Ebstein's
      malformation is associated with a poor outcome. Moreover, the echocardiographic
      appearance, marked cardiomegaly, and the presence of associated lesions are all
      risk factors for mortality. Arrhythmia and need of medical treatment are common
      in older children and adults. Survival after surgical treatment is associated
      with a good outcome.

PMID- 15237673
TI  - The Warden procedure for partially anomalous pulmonary venous connection to the
      superior caval vein.
AB  - PURPOSE: When there is partially anomalous pulmonary venous connection to the
      superior caval vein, intracardiac repair alone can result in obstruction.
      Although the Warden procedure involving translocation of the superior caval vein
      is commonly performed as an alternative to atriocavoplasty, follow-up of a larger
      number of patients in the modern era is lacking. We report and discuss the
      experience of a single institution with the Warden procedure for correction of
      partially anomalous pulmonary venous connection to the superior caval vein.
      METHODS: Since 1995, all 16 patients presenting with partially anomalous
      pulmonary venous connection to the superior caval vein underwent the Warden
      procedure at a mean age of 7.1 +/- 4.2 years, with a range from 0.2 to 14.3
      years, and a mean weight of 24.7 +/- 14.0 kg, with a range from 4.1 to 52.9 kg.
      There were 9 males and 7 females. In 8 patients, we performed 10 concomitant
      procedures, including closure of an atrial or ventricular septal defect in 7, and
      advancement of the aortic arch in the other. RESULTS: There were no deaths, and
      only one episode of postoperative sinus bradycardia with intermittent junctional
      rhythm, which resolved spontaneously during temporary atrial pacing. All patients
      were discharged home in normal sinus rhythm at an average of 4.1 +/- 2.2 days
      after the procedure, with a range from 2 to 10 days. All are currently in the
      first grade of the New York Heart Association up to 5.6 years postoperatively.
      There is currently no evidence of sinus nodal dysfunction, nor obstruction of the
      superior caval vein, in any patient. CONCLUSION: The Warden procedure for
      partially anomalous pulmonary venous connection to the superior caval vein
      produces excellent results, preserves the function of the sinus node, and should
      be routinely considered for the repair of this lesion.

PMID- 15237675
TI  - Alexander Sandor Nadas: November 12, 1913 - May 15, 2000.

PMID- 15237674
TI  - Prevalence of arrhythmias and conduction disturbances in large population-based
      samples of children.
AB  - The aim of our study is to provide data on the prevalence of disturbances of
      rhythm in the general population of children. Accurate estimates of true
      prevalence of such disturbances of rhythm from large samples are mandatory if we
      are to interpret properly electrocardiographic abnormalities. We analysed
      prevalence of disturbances of rhythm in a population of 152,322, comprised of
      71,855 elementary school students, 36,692 males and 35,163 females, aged from 5
      to 6 years, and 80,467 students of junior high school, 41,842 males and 38,625
      females, aged from 12 to 13 years. We analysed the prevalence of premature atrial
      and ventricular contractions, first, second and third degree atrioventricular
      block, incomplete and complete right bundle branch block, Wolff-Parkinson-White
      syndrome, and prolongation of the QT interval. The prevalence of disturbances of
      rhythm in total rose with age, being found in 1.25% of elementary school students
      and 2.32% of junior high school students, and was higher in males than females,
      at 2.00% as opposed to 1.38%, both values being statistically significant at a
      level of less than 0.0001. Prevalences of all types of rhythmic disturbances were
      higher in junior high school students than elementary school students (p <
      0.0001). Premature atrial and ventricular contractions and prolongation of the QT
      interval were higher in female than male students, at percentages of 0.089,
      0.497, and 0.02 for males, and 0.123, 0.534 and 0.027 in females (p < 0.0001). In
      contrast, incomplete and complete right bundle branch blocks were higher in males
      than females, at 0.983% and 0.083% in males versus 0.410% and 0.161% in females
      (p < 0.0001). Disturbances of rhythm increased with age, and conduction
      disturbances were higher in male students than female, although premature atrial
      and ventricular contractions and prolongation of the QT interval were more
      frequent in female. These data may be useful for future comparative studies of
      disturbance of rhythm in children.

PMID- 15237676
TI  - Cutaneo-mediastinal sinus following construction of the Fontan circulation with
      an adjustable fenestration.

PMID- 15237677
TI  - Acute chest pain in a young adult.

PMID- 15237678
TI  - Aortic-right atrial tunnel.
AB  - We describe an asymptomatic 1-year-old boy who presented a continuous murmur, and
      was found to have a tunnel between the right atrium and the aorta. The definitive
      diagnosis was established by both echocardiography and aortography, and surgical
      interruption of the tunnel was successful. We emphasise the rarity of this
      condition, and discuss its major features.

PMID- 15237679
TI  - Myotonic dystrophy presenting as atrial flutter in childhood.
AB  - A 12-year-old boy presented with tachycardia and cardiomegaly. An
      electrocardiogram showed atrial flutter with a ventricular rate of 170 beats/min.
      The echocardiogram showed left ventricular dilation, with decreased
      contractility. Electromyography confirmed the diagnosis of myotonic dystrophy.
      The atrial flutter was converted to sinus rhythm by electroversion, leading to
      restoration of normal cardiac function. Our case illustrates that atrial flutter
      can be an early sign of the cardiac complications of myotonic dystrophy in
      childhood.

PMID- 15237680
TI  - Intraoperative rescue by placement of a stent following a surgical coronary
      arterial injury in a child.
AB  - An acute injury to a coronary artery was recognized during the surgical
      construction of the Fontan circulation. Surgical manipulation of the site of
      injury was not successful in restoring normal myocardial blood flow. A stent was
      therefore placed intraoperatively under direct vision, with restoration of normal
      coronary arterial flow acutely and at short-term follow-up.

PMID- 15237681
TI  - Anomalous origin of the circumflex coronary artery in a patient with atrial and
      ventricular septal defects.
AB  - We report a patient in whom the circumflex coronary artery arose anomalously from
      the right aortic sinus. The patient also had atrial and ventricular septal
      defects in the setting of Eisenmenger physiology. We recommended transplantation
      of the heart and lungs.

PMID- 15237682
TI  - An obstructive bicuspid aortic valve in the setting of tetralogy of Fallot with
      pulmonary atresia: a rare combination.
AB  - As far as we are aware, a bicuspid aortic valve has not previously been reported
      in the setting of tetralogy of Fallot and pulmonary atresia. We describe this
      association in a newborn who presented with a murmur and cyanosis.
      Echocardiography showed tetralogy of Fallot with pulmonary atresia, and also a
      moderately stenotic bicuspid aortic valve. The patient underwent open-heart
      surgery guided by transesophageal echocardiography. Postoperatively, there was
      only mild obstruction across both outflow tracts. We have also reviewed the
      pertinent data from our Jesse E. Edwards Registry of Cardiovascular Disease to
      establish the incidence of bicuspid aortic valve in the setting of obstruction of
      the right ventricular outflow tract, finding the association in no patients with
      pulmonary atresia and tetralogy of Fallot, in 0.7% of those with tetralogy of
      Fallot and pulmonary stenosis, but in 6.6% of those with pulmonary atresia and
      intact ventricular septum.

PMID- 15237683
TI  - Echocardiographic characteristics of venous air embolism presenting as reversible
      pulmonary atresia in a premature neonate.
AB  - Air embolism secondary to mechanical ventilation is a rare but well-described
      complication in premature infants. We describe the echocardiographic appearance
      of venous air embolism manifesting as acute obstruction of the right ventricular
      outflow tract in such a premature infant, and review the pathophysiology of acute
      obstruction of the right ventricular outflow tract secondary to the "air lock"
      phenomenon. Awareness of the pathophysiology and echocardiographic appearance of
      venous air embolism may aid in prompt recognition and potential therapy for this
      lethal complication of mechanical ventilation.

PMID- 15237684
TI  - Resection of a cardiac aneurysm in an infant with anomalous origin of the left
      coronary artery from the pulmonary trunk.
AB  - We describe an infant with an anomalous left coronary artery arising from the
      pulmonary trunk leading to myocardial ischaemia and development of an apical
      aneurysm of the left ventricle. Clinical presentation in general is based on
      myocardial hypoperfusion resulting in ischaemia and infarction. When presenting
      in infancy, however, then the features, as in our patient, may be tachypnea,
      dyspnea, failure to thrive and irritability, especially during feeding. Then,
      again as in our patient, it is possible to miss the definitive diagnosis, which
      is made by echocardiography and cardiac catheterization. Reimplantation of the
      anomalous left coronary artery into the aorta usually results in improvement of
      left ventricular function over time. In our patient, the myocardial infarction
      was complicated by formation of an aneurysm, and reimplantation alone was not
      sufficient to restore cardiac function. Resection of the aneurysm greatly
      improved the hemodynamics.

PMID- 15237685
TI  - Recommendations for the practice of fetal cardiology in Europe.

PMID- 15237686
TI  - Re: Optimal timing of the Ross procedure.

PMID- 15237687
TI  - Thrombolytic therapy in morbidly obese patients.
AB  - Most of the concern about dosing thrombolytic agents as presented in the
      literature is related to the lower weight groups and the increased incidence of
      bleeding in this patient population. Not much is known or written about what dose
      of thrombolytic therapy should be used in the grossly obese patient with an AMI.
      Although it may be uncommon to have a morbidly obese patient with an AMI, it does
      occur. Perhaps body weight doesn't matter since we are really dosing the clot and
      not the body, but, as far as I can discern, there are no data regarding dosing of
      thrombolytic drugs to guide the clinician managing these patients.

PMID- 15237688
TI  - The decision to anticoagulate: assessing whether benefits outweigh the risks for
      patients with atrial fibrillation.
AB  - In a review of relevant articles from the Medline database on stroke risk in
      atrial fibrillation (AF) and adverse events related to anticoagulation treatment,
      we found that research to date shows a major potential benefit of warfarin
      therapy (International Normalized Ratio [INR] 2.0-3.0) for patients with AF (68%
      risk reduction in primary stroke prevention with warfarin vs. placebo). Despite
      this highly significant reduction in stroke risk, fewer than 50% of eligible
      patients are treated, in many cases because of fears of intracranial hemorrhage
      (ICH). The decision to implement anticoagulant therapy to improve outcome
      requires balancing the decreased risk for stroke against the increased risk for
      ICH. Various methods have been developed to define patient-specific stroke risk.
      In contrast, risk for ICH strongly correlates with the intensity of
      anticoagulation, which is an unpredictable but controllable variable requiring
      frequent dose adjustments. Recent studies have also identified subgroups of
      patients with neurologic pathologies who are at increased risk for ICH. However,
      when the INR is properly controlled, the benefit from anticoagulation therapy for
      patients with AF and other risk factors for stroke exceeds the risk for ICH.
      Careful monitoring of anticoagulation and warfarin dose titration to maintain the
      INR between 2.0 and 3.0 is critical for reducing the risk for ICH, as is
      excluding patients with neurologic conditions that increase the likelihood of
      ICH. Future developments, such as the introduction of oral direct thrombin
      inhibitors with more predictable pharmacokinetics than warfarin, may further
      improve the benefit-to-risk ratio of anticoagulation therapy for patients with
      AF.

PMID- 15237689
TI  - Panic disorders and agoraphobia: side effects of treatment with an implantable
      cardioverter/defibrillator.
AB  - BACKGROUND: Implantable cardioverter/defibrillator (ICD) treatment has reduced
      the mortality of patients with a high risk of sudden cardiac death. However, ICD
      discharges may cause anxiety with respect to new discharges and lead to
      preventive, for example, phobic, behavior. This study evaluated the frequency of
      panic disorders and agoraphobia in patients with ICD and assessed the risk
      factors in their development. HYPOTHESIS: Treatment with ICD represents a risk
      factor in the development of anxiety disorders. METHODS: Ninety patients with ICD
      were examined using a standardized lifetime Diagnostic Interview of Psychiatric
      Syndromes (DIPS). This interview makes it possible to estimate the incidence of
      panic disorders and agoraphobia. The impact of the severity of the underlying
      cardiac disease, the number of ICD discharges, and the subjective appraisal of
      the shock experience on the development of panic disorders and agoraphobia was
      assessed. RESULTS: Fifteen patients (16.7%) developed anxiety disorders after ICD
      implantation. The incidence was 21% in patients with and 6.9% in patients without
      ICD discharge. In patients with two or more ICD discharges annually, the
      incidence of panic disorders and agoraphobia was higher than that in patients
      with a single ICD discharge annually (62 vs. 10%, p<0.01). The intensity of self
      observation of their body was significantly related to the development of anxiety
      disorders (p<0.001). CONCLUSION: Panic disorders and agoraphobia are frequent
      side effects of ICD treatment. Risk factors in the development of these disorders
      are two or more ICD discharges annually and a negative cognitive appraisal of ICD
      discharges. Therapeutic efforts should aim at reducing the number of ICD
      discharges and provide early psychological treatment.

PMID- 15237690
TI  - Preventive therapy in patients with insignificantly narrowed coronary arteries:
      evaluation of physician attitude and practice.
AB  - BACKGROUND: Although the outcome of patients with angiographically
      insignificantly narrowed coronary arteries (INCA) is not clearly defined, such
      lesions can progress or rupture, thus causing cardiovascular morbidity.
      Preventive therapy with aspirin and lipid-lowering drugs therefore seems
      warranted in these patients. HYPOTHESIS: The study was undertaken to evaluate the
      attitude and practice of physicians toward the provision of preventive treatment
      to patients with INCA. METHODS: The attitude of physicians was evaluated using
      written case histories of three patients with identical clinical features but
      different angiographic diagnoses. We then examined randomly chosen files of 130
      patients with angiographically normal coronary arteries, 130 patients with INCA,
      and 130 patients with significant coronary artery disease, in relation to the use
      of lipid-lowering medications and achieved lipoprotein levels. RESULTS: For the
      hypothetical patients, more physicians prescribed statins (78 vs. 47%, p<0.0001)
      and aspirin (89 vs. 74%, p<0.003) for patients with significant disease than they
      did for those with INCA. A target low-density lipoprotein (LDL) cholesterol of <
      100 mg/dl was considered appropriate for significant disease by 85% of physicians
      compared with 40% for INCA (p<0.0001). In the real patients, more of those with
      significant disease received lipid-lowering drugs and achieved the LDL target
      level than did those with INCA. CONCLUSIONS: Many physicians regard the need to
      prescribe preventive treatment as less important for patients with INCA than for
      patients with significant coronary disease. Additional long-term studies are
      warranted to elucidate the prognostic significance of INCA and the efficacy of
      preventive therapy in these patients.

PMID- 15237691
TI  - Impact of left ventricular ejection fraction on endothelial function in patients
      with coronary artery disease.
AB  - BACKGROUND: Endothelial dysfunction is present in patients with coronary artery
      disease (CAD) or with congestive heart failure. HYPOTHESIS: This study was
      performed to evaluate the impact of systolic heart function on endothelial
      function in patients with CAD. METHODS: The study population consisted of 283
      consecutive patients (mean age 59 years, 176 men) undergoing coronary
      angiography. Endothelial function was assessed by measuring flow-mediated
      vasodilation (FMD) of the brachial artery. RESULTS: Patients (n = 236) with an
      ejection fraction (EF) > or = 55% on routine echocardiogram were younger (mean
      age 58 vs. 62 years), showed a lower prevalence of diabetes (15 vs. 38%) and
      myocardial infarction (13 vs. 66%), and showed a higher FMD (4.8 +/- 2.4 vs. 4.0
      +/- 2.0%, p < 0.05) than patients (n = 47) with an EF < 55%. The correlation
      coefficient between FMD/endothelial function and EF/systolic heart function was
      0.149 (p < 0.02) in the overall study population. Multivariate analysis showed
      that of age, gender, frequency of diabetes mellitus, myocardial infarction, and
      CAD extent, EF was the only significant independent parameter correlating with
      FMD in patients with CAD. CONCLUSIONS: Compared with the other tested risk
      factors, EF surprisingly was the only significant independent parameter
      correlating with endothelial function in patients with CAD. Our results support
      the view that endothelial function is an independent prognostic factor in
      patients with CAD.

PMID- 15237692
TI  - Coronary-pulmonary fistulae arising from multiple coronary arteries.

PMID- 15237693
TI  - High remnant lipoprotein levels in patients with variant angina.
AB  - BACKGROUND: Dyslipidemia with increased oxidative stress but without elevation of
      low-density lipoprotein cholesterol has been recently implicated in the
      pathogenesis of coronary vasospasm. HYPOTHESIS: Disordered triglyceride-rich
      lipoprotein metabolism may be linked to the genesis of coronary artery spasm.
      METHODS: Both serum remnant lipoprotein (RLP) and alpha-tocopherol levels were
      determined in 18 patients with the active stage of variant angina (VA), in 16
      patients with the inactive stage of variant angina (IVA), and in 19 control
      subjects (CONTROL). RESULTS: The RLP levels were significantly (p < 0.05) higher
      in VA (6.4 +/- 2.7 mg/dl) than in IVA (4.4 +/- 1.5 mg/dl). In contrast, alpha
      tocopherol levels were significantly lower in VA than that in CONTROL. Serum
      trigyceride levels were not significantly different among the study groups,
      although serum high-density lipoprotein cholesterol levels were significantly
      lower in VA than in CONTROL. Smoking was significantly (p < 0.05) more prevalent
      in VA (72%) than in IVA (25%) and CONTROL (37%). Serum RLP levels correlated
      positively with triglyceride levels (R = 0.73) and correlated inversely with
      alpha-tocopherol levels (R = -0.31) significantly in all study subjects.
      CONCLUSIONS: Patients with active stage of variant angina had higher RLP levels
      than inactive patients with variant angina and lower alpha-tocopherol levels than
      control subjects. Disordered triglyceride-rich lipoprotein metabolism with
      increased oxidative stress appears to be linked to the activity of coronary
      vasospasm, suggesting a possible role in its pathogenesis.

PMID- 15237694
TI  - Role of endogenous adenosine in atrial fibrillation after coronary artery bypass
      graft.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common complication following
      coronary artery bypass graft (CABG). The mechanism of AF after CABG is not well
      defined; however, it is suggested that endogenous adenosine, released in response
      to tissue hypoxia, may play a mechanistic role in these arrhythmias. HYPOTHESIS:
      The purpose of this study was to examine whether intravenous theophylline, via
      adenosine A1 receptor antagonism, would correct or modify new-onset early (<48 h
      post CABG) atrial fibrillation in patients post CABG, and thereby implicate
      endogenous adenosine as an inciting agent. METHODS: A prospective double-blind,
      placebo-controlled study design was applied to 385 consecutive patients with
      coronary artery disease who had undergone CABG. Any patient who developed AF
      within 48 h of the operative procedure was randomly assigned to receive 5 mg/kg
      of intravenous theophylline (Group A) or matched intravenous placebo (Group B).
      The patients who converted to sinus rhythm within 15 min of drug administration
      were accepted as showing positive responses. RESULTS: Thirty patients comprised
      the study group. In Group A, 8 of the 15 patients (53%) converted from AF to
      sinus rhythm within 15 min of theophylline administration. One patient who
      converted to sinus rhythm 20 min after theophylline administration was accepted
      as showing a negative response. In the placebo-treated group, no patient
      converted to sinus rhythm within 15 min (p<0.007 compared with Group A).
      CONCLUSIONS: The mechanism of AF after CABG is not well defined and is probably
      multifactorial. However, this study demonstrated that antagonism of the adenosine
      A1 receptor can promptly convert many of these patients back to sinus rhythm, and
      thereby implicates endogenously released adenosine in a mechanistic role for
      inciting early (<48 h) post-CABG AF.

PMID- 15237695
TI  - Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic
      receptor blockade in patients with essential hypertension.
AB  - BACKGROUND: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the
      beta1-adrenergic receptor might be of functional importance for the
      cardiovascular system. Both have been associated with altered receptor activity
      in vitro, and with hypertension and cardiac failure in vivo. HYPOTHESIS: The aim
      of this study was to test whether these polymorphisms were associated with the
      change in heart rate or blood pressure in patients with essential hypertension
      and left ventricular (LV) hypertrophy treated with the beta1-adrenergic receptor
      blocker atenolol. METHODS: Blood pressure and heart rate were measured in 101
      hypertensive patients with echocardiographically verified LV hypertrophy,
      randomized in a double-blind study to treatment with either the beta1-adrenergic
      receptor blocker atenolol or the angiotensin II type I receptor antagonist
      irbesartan. Changes in blood pressure and heart rate were evaluated after 12
      weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain
      reaction and restriction fragment length polymorphism. RESULTS: We found no
      significant associations between the changes in the measured variables and either
      of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency
      toward a greater reduction in heart rate compared with patients with the
      Ser/Ser49 genotype (p = 0.06). CONCLUSIONS: The Ser49Gly and Arg389Gly beta1
      adrenergic receptor polymorphisms do not seem to exert a major effect on the
      changes in heart rate and blood pressure during 12 weeks of treatment with
      atenolol in patients with essential hypertension and LV hypertrophy.

PMID- 15237696
TI  - Evaluation of myocardial performance index to predict mild rejection in cardiac
      transplantation.
AB  - BACKGROUND: Early diagnosis of heart transplant rejection is mandatory, since
      even mild rejection can rapidly progress to more severe rejection. Noninvasive
      diagnosis of heart transplant rejection still remains a challenge. HYPOTHESIS:
      The purpose of the study was to determine a possible association between
      myocardial performance index (MPI) and biopsy score of the heart transplant.
      METHODS: This is a retrospective cohort analysis of 99 complete Doppler
      echocardiographic studies from 24 consecutive patients (23 men) performed within
      24 h of endomyocardial biopsy. Mean age of the cohort was 50 +/- 9 years and mean
      time from transplantation was 19 +/- 21 months (1-81). All patients were in sinus
      rhythm. Myocardial performance index was calculated as the ratio of isovolumic
      contraction time plus isovolumic relaxation time divided by ejection time. Left
      ventricular dimensions, left ventricular mass, ejection fraction, and a number of
      Doppler indices (E-point velocity, A-point velocity, deceleration time, and
      deceleration slope) were also measured. The International Society for Heart and
      Lung Transplantation (ISHLT) grading system was used for the classification of
      endomyocardial biopsies. RESULTS: Myocardial performance index was significantly
      prolonged (0.60 +/- 0.13, 0.68 +/- 0.08, 0.75 +/- 0.20, in biopsy scores 0, IA,
      and IB, respectively; p<0.001). Isovolumic contraction time was significantly
      prolonged; isovolumic relaxation time was not significantly changed. Ejection
      time and deceleration time were significantly shortened. Multivariate stepwise
      regression analysis revealed that MPI and deceleration time were the only
      independent predictors of biopsy score (r=0.48, F=10.53, p<0.0001). CONCLUSION:
      Myocardial performance index seems to be a useful adjunct in the follow-up of
      cardiac transplant patients. These preliminary data suggest that a larger study
      may be indicated to clarify the relevance of myocardial performance index.

PMID- 15237697
TI  - Isolated pulmonary arterial pulsus alternans secondary to pulmonary hypertension.

PMID- 15237698
TI  - Ibutilide-induced alterations in electrocardiographic and spatial
      vectorcardiographic descriptors of ventricular repolarization.
AB  - BACKGROUND: Ibutilide is used for the pharmacologic cardioversion of atrial
      fibrillation (AF) or flutter (AFl). Ibutilide-induced QT interval prolongation
      has been demonstrated previously. However, its effects on vectorcardiographic
      (VCG) descriptors of ventricular repolarization (VR) have not been studied so
      far. HYPOTHESIS: To evaluate the effects of ibutilide on electrocardiographic
      (ECG) and VCG descriptors of VR, one or two repeated 10-min infusions of 1 mg of
      ibutilide were given in 50 consecutively recruited patients (36 women, mean age
      69.4 +/- 9.3 years) with AF or AFl of recent onset. METHODS: The maximum and the
      minimum QT intervals, QT dispersion, the rate-corrected QT maximum, and the
      spatial VCG descriptors, spatial T amplitude, and spatial QRS-T angle were
      calculated before (baseline ECG) and 30 min after the start of ibutilide infusion
      (postinfusion ECG). RESULTS: After ibutilide infusion, 40 (80%) patients were
      cardioverted to sinus rhythm (Group 1), while in the remaining 10 (Group 2) AF or
      AFl persisted. In both study groups, temporal measures of VR were significantly
      increased from baseline to the postinfusion ECG. In Group 1, spatial T amplitude
      and spatial QRS-T angle did not differ between those two ECGs, while in Group 2
      spatial T amplitude was significantly increased (p = 0.005) and spatial QRS-T
      angle was significantly decreased (p = 0.002) post infusion compared with
      baseline ECG. CONCLUSIONS: While temporal measures of VR are significantly
      affected in all patients who receive ibutilide infusion for AF or AFl
      cardioversion, spatial VCG descriptors of VR are significantly altered only in
      those patients who fail to respond to the drug. A dose-related effect of
      ibutilide on the different aspects of VR should be suspected.

PMID- 15237699
TI  - Primary extramedullary plasmacytoma of the heart.

PMID- 15237700
TI  - Percutaneous mitral commissurotomy using the metallic valvulotome technique in a
      critically ill adult.
AB  - A 25-year-old man presented with cardiogenic shock secondary to rheumatic mitral
      stenosis. Despite aggressive medical treatment he continued to deteriorate. This
      report describes the successful use of the metallic valvulotome technique for
      mitral commissurotomy in the context of a critically ill patient.

PMID- 15237701
TI  - Attilio Maseri.
AB  - Professor Attilio Maseri is a clinical investigator with a remarkable track
      record of innovative research who, by changing traditional paradigms, contributed
      to shape new diagnostic techniques in pathophysiologic thinking. His research has
      been characterized by challenging the generalizations of accepted "wisdom" which
      did not offer satisfactory explanations for the observations he made in his
      clinical practice. The results of his clinical investigations have contributed
      greatly to the opening of new avenues of research and patient management in the
      field of ischemic heart disease. His clinical and research experiences are
      catalogued in 740 pages of his single-authored textbook Ischemic Heart Disease. A
      Rational Basis for Clinical Practice and Clinical Research. This book chronicles
      Maseri's novel unifying vision of ischemic heart disease. In 2001, Professor
      Maseri left Catholic University in Rome to take on bigger challenges in Milan
      where he is now functioning as Professor of Cardiology at the University Vita
      Salute San Raffaele and Director of the Cardio-Thoracic and Vascular Department
      of the San Raffaele Scientific Institute. His research interests include
      application of molecular biology, differential gene expression profiling, and
      clinical cardiovascular research such as molecular mechanisms of coronary
      instability and molecular mechanisms of negative and positive ventricular
      remodeling. Professor Attilio Maseri will be remembered as a thoughtful
      clinician, a mentor for many whose academic careers have blossomed, and a careful
      clinical investigator whose innovative research in ischemic heart disease will
      set the highest standards for those who follow in his giant footsteps. On a
      personal note, I first met Attilio Maseri, his wife Francesca, and their son
      Filippo at the 1976 Pisa conference. What transpired at that conference
      influenced my own career and stimulated my continued interest in ischemic heart
      disease as well as my enthusiasm for the international aspects of cardiovascular
      medicine. I consider myself fortunate to be a friend of Attilio Maseri and to
      have benefited from my associations with him, both professionally and personally.

PMID- 15237702
TI  - Feminizing genitoplasty: a synopsis of issues relating to genital surgery in
      intersex individuals.
AB  - This review of the literature relevant to genitoplasty explores multiple factors
      that could impact and improve long-term outcomes. In 1998, surgeons began a
      dialogue that fostered interactive multidisciplinary exchanges regarding
      necessity, timing, and risks related to genitoplasty. Prior practice had embraced
      a simplistic approach--make an intersexed child resemble either a typical boy or
      girl. But surgery was never 'perfect' because function was often sacrificed for
      form, the goal being to create an aesthetic appearance. Compounding the
      difficulties of this type of surgery were the demands of the patients and parents
      for clarity, sure direction, and surgery that looked cosmetically authentic and
      provided good function. They demanded answers that medical experts could not
      readily provide regarding long-term outcomes. To increase patient satisfaction,
      we seek such outcomes and knowledge to better our understanding for optimal
      patient management and care. A review of current research is provided that might
      have important implications impacting surgical issues. Knowledge garnered from
      fields other than surgery is explored for potential applications that could
      improve surgical outcomes. Surgical technique modifications may be part of the
      solution to a complex problem, but they are not the sole solution. A
      multidisciplinary approach is required because to this date, surgical promise is
      limited at best. Better understanding of the anatomy and physiology, as well as
      the related hormonal environment and its impact on healing, may be the key toward
      improvement of outcomes and heightened patient satisfaction.

PMID- 15237703
TI  - Which treatment options should be used in adolescents with polycystic ovary
      syndrome?
AB  - Several studies have hypothesized a peripubertal onset of polycystic ovary
      syndrome (PCOS). This syndrome affects different pathogenetic pathways and
      includes endocrine-metabolic abnormalities such as hyperandrogenism,
      hyperinsulinism and insulin resistance. The therapeutic approaches must be
      addressed to individualization of therapy, considering the major clinical
      manifestations of the syndrome during adolescence. While the treatment of
      hyperandrogenism makes use of different drugs already studied, the debate about
      the use of insulin sensitizing drugs is still open. It will be more and more
      necessary to define the phenotypic and genotypic milieu in which all treatments
      will be as safe and effective as possible.

PMID- 15237704
TI  - Auxologic and biochemical characterization of the three phases of growth failure
      in pediatric patients with brain tumors.
AB  - Pediatric patients with brain tumors can loose 1 SD of height prior to beginning
      growth hormone (GH) therapy. The objectives of this study were to characterize
      the early growth failure, identify contributing factors and propose
      interventions. Five children were followed quarterly for 2 years to monitor
      auxological parameters, nutritional indices, and endocrine measuremnts. GH
      stimulation tests were done every 6 months to determine the timing of the onset
      of GH deficiency. The nadir for height velocity (HV) occurred 6 months after
      diagnosis. Poor gains in height correlated with decreased calorie count (p
      <0.001), poor weight gain (p <0.001), decreased BMI (p <0.001) and lowered leptin
      levels (p <0.001). All patients were able to secrete GH normally during this
      nadir of growth. Children treated for brain tumors demonstrate an early triphasic
      pattern of growth. Growth failure due to cachexia occurs first, then a second
      transient phase of normal growth is observed followed by a third phase of growth
      failure due to GH deficiency. Phase 1 is characterized by decreased HV, BMI,
      leptin levels and calorie counts. With recognition of this profile, the early
      growth failure might be preventable with aggressive nutritional rehabilitation.

PMID- 15237705
TI  - Growth patterns and final height of survivors of childhood leukemia.
AB  - Growth patterns of 85 survivors of childhood leukemia were analyzed
      retrospectively. All patients remained in first remission with no central nervous
      system involvement. The mean age at diagnosis was 5.8 +/- 3.6 years. The
      diagnoses were acute lymphoblastic leukemia (ALL) in 68 patients (80%) and acute
      non-lymphoblastic leukemia (ANLL) in 17 patients (20%). All except two patients
      received cranial irradiation: 51 patients with 1,800 cGy and 32 patients with
      2,400 cGy. Mean height SDS was -0.7 +/- 1.36 at the time of diagnosis, which
      decreased to -0.92 +/- 1.31 by the end of treatment, and further decreased to 
      1.14 +/- 1.38 at 6 years after cessation of treatment. Mean weight SDS was -0.55
      +/- 1.13 at the time of diagnosis, increasing slightly to -0.39 +/- 1.02 at the
      end of treatment, and decreasing to -0.46 +/- 1.65 at 6 years after cessation of
      treatment. Of these survivors, 51 patients (26 boys and 25 girls) reached a final
      height that was 1.04 SDS or 5.3 cm less than their target height. There was no
      difference of height and weight SDS between patients with ALL and ANLL. Girls and
      boys had different growth patterns. Girls had a slightly increased height SDS and
      gained more weight after cessation of treatment, resulting in less final height
      deficit and overweight for height, whereas boys had further height and weight
      reduction resulting in more deficit of final height.

PMID- 15237706
TI  - Insulin gene profile cycles with season of birth of future diabetic children and
      their relatives.
AB  - BACKGROUND: HLA class II gene pattern and IA-2A antibody positivity, revealing
      selected risks for prediction of type 1 diabetes mellitus (DM1), were previously
      shown to be cycling roughly in parallel with seasonally fluctuating frequencies
      of births of future diabetic children. Is this also true for insulin genotyping?
      Is this also true for births of the healthy close relatives of children with DM1?
      PATIENTS AND METHODS: In 98 Slovak children with DM1 and in 60 healthy parents
      and siblings, two single nucleotide polymorphisms of the insulin gene (-23 Hph I;
      +1127 Pst I) were typed. Results were expressed as score 0 (maximal risk) up to 2
      (minimal risk or protection), or 0-4 for the sum of both scores. Birth
      seasonality of these risk scores was tested by Halberg cosinor regression.
      RESULTS: Results were similar for the two alleles; therefore, the summed risk
      score was evaluated. The DM1 risk from the insulin gene pattern in births of
      future diabetics cycled significantly semi-annually, with maxima around the
      spring and autumn equinoxes. In the relatives, a significant annual and extremely
      pronounced quarterly peaking rhythm was found, with maximum risk in births around
      the autumn equinox and shortly after the winter solstice. Significant protection
      peaks are present in late winter, spring and summer. CONCLUSION: The highest
      frequency of Coxsackie infections in the Slovakian child population, and of
      'diabetic' births and manifestations, found earlier together with maximal risks
      from HLA II and IA-2A antibodies in late summer and early autumn, is now
      confirmed also for the insulin gene pattern in diabetic children and even also
      for their healthy close relatives.

PMID- 15237707
TI  - Analysis of cytotoxic T lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism in
      patients with type 1 diabetes mellitus in a Turkish population.
AB  - Recent studies have described linkage and association between cytotoxic T
      lymphocyte antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus
      (DM1) in some ethnic populations, but not others. This finding suggests that CTLA
      4 gene association with DM1 may be influenced by the racial composition of the
      population. Thus, it is important to study the polymorphism of the CTLA-4 gene in
      different ethnic groups. In this case-control association study, the CTLA-4 gene
      exon 1 A/G polymorphism was analyzed in 48 children with DM1 and 80 healthy
      controls using polymerase chain reaction-restriction fragment length polymorphism
      analysis. The possible interaction of the CTLA-4 gene polymorphism with the
      presence of established genetic markers (HLA-DR genotyping) was also evaluated in
      29 patients. The results of the present study do not suggest an association of
      the known polymorphism in exon 1 of the CTLA-4 gene with DM1 in this Turkish
      population, and G-allele containing CTLA-4 genotypes were not preferentially
      associated with age at clinical presentation or with presence of other genetic
      (HLA-DR3 or -DR4) markers of DM1.

PMID- 15237708
TI  - Relationship between cord blood levels of IGF-I and ferritin in healthy term
      neonates.
AB  - OBJECTIVE: We hypothesize that the balance of maternal and fetal insulin-like
      growth factor-I (IGF-I) concentrations contributes to the regulation of substrate
      distribution between mother and fetus, and may thus mediate the maintenance of
      blood ferritin concentration in the fetus. Therefore, the relationship between
      cord blood IGF-I to ferritin concentration was investigated. INFANTS AND METHODS:
      Twenty-six term neonates were recruited. Anthropometric measures were recorded
      and umbilical cord blood samples were collected at birth. We studied serum
      concentrations of IGF-I in relation to blood ferritin and anthropometric data in
      term neonates. To assess the importance of the correlation of ferritin with both
      IGF-I and all other parameters, multiple linear regression analysis was carried
      out, with ferritin as the dependent variable and IGF-I and anthropometric
      parameters as independent variables. RESULTS: The mean concentrations of cord
      blood IGF-I and ferritin levels were 45.2 +/- 36.8 ng/ml and 225.5 +/- 124.2
      ng/ml, respectively, at birth. A positive correlation was observed between IGF-I
      and ferritin concentrations of term neonates (r = 0.53, p = 0.005). IGF-I emerged
      as a significant predictor of ferritin concentration (beta = 1.79, p = 0.005)
      contributing to 28% of its variability. CONCLUSIONS: We showed a relationship
      between cord blood IGF-I and ferritin levels in term neonates, suggesting that
      even within an unremarkable population, fetal ferritin level may be influenced by
      IGF-I. Moreover, we speculated that IGF-I might also be important in the
      regulation of placental transport of ferritin.

PMID- 15237709
TI  - Dual growth hormone (GH) response to repeated GH releasing hormone stimulus in
      children and adults.
AB  - Several authors have demonstrated that plasma growth hormone (GH) levels as
      response to acute GH releasing hormone (GHRH) stimulation in adults are decreased
      by a previous GHRH injection whereas they are maintained in children. Probably
      the most accepted hypothesis for this finding is the increase in the
      somatostatinergic tone. The aim of the present study was to evaluate the dual GH
      response to repeated GHRH stimuli to clarify the possible influence of
      somatostatinergic activity in the type of response. Eighteen healthy prepubertal
      children, mean age 9.2 years (range: 6.0-12.9 years) and 19 healthy adult
      volunteers, mean age 25.5 years (range: 17-35 years) were studied with the GHRH
      test. An additional group of 10 normal adults with similar characteristics (mean
      age 31 years, range 25-35 years) were also recruited as a control group for
      somatostatinergic assessment. The GH response to the first GHRH bolus was similar
      in both children and adults. However, while children showed a preserved response
      to the second stimulus, it was diminished in adults. As expected, thyroid
      stimulating hormone (TSH) was within the normal range in all subjects. When the
      evolution of TSH was compared between the group of non-responders and the control
      group, no significant differences were found either at basal time or at 120 min,
      showing a similar decreasing trend for serum TSH level. The variation of TSH
      levels were also expressed as the proportion of TSH response after 2 hours
      compared to the basal level (TSH-120/TSH-0) but no significant differences were
      found (GHRH non-responders group mean: 73.6%, range: 51.3-93.7; control group
      mean: 70.7%, range: 62.9-92.5). In conclusion, the results confirm that in adults
      but not in children, the somatotrope responsiveness to GHRH is inhibited by a
      previous bolus of GHRH. The finding that the plasma TSH level diminishes in a
      similar manner in both non-responders and the control group is in agreement with
      the rejection of the hypothesis of the influence of somatostatin.

PMID- 15237710
TI  - Differential impact of simple childhood obesity on the components of the growth
      hormone-insulin-like growth factor (IGF)-IGF binding proteins axis.
AB  - Simple childhood obesity is characterized by normal or even accelerated growth in
      spite of reduced growth hormone (GH) secretion. There are conflicting reports on
      the effects of obesity upon components of the GH-insulin-like growth factor-I
      (IGF-I)-IGF binding proteins (IGFBPs) system. In the present study we aimed to
      determine GH, IGF-I, IGFBP-3 and IGFBP-2 as well as some of the less explored
      components of this axis (IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments,
      and total acid labile subunit [ALS]) in 22 obese and 17 age-matched control
      children. We also evaluated not only total GH binding protein (GHBP) serum levels
      but also GHBP bound to GH (complexed) in both groups. Obese and control groups
      strongly differed in BMI (obese: 4.7 +/- 0.36 vs control: 0.37 +/- 0.25 SDS, p
      <0.0001). In the obese group, we found lower GH serum levels, but normal serum
      levels of GH-GHBP complex, IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, IGFBP-3
      proteolytic activity, IGFBP-3 plasma fragments and total ALS. Obese children
      presented higher total circulating GHBP (6.0 +/- 0.44 vs 2.9 +/- 0.29 nmol/l, p
      <0.001) and insulin levels (10.5 +/- 1.5 vs 5.1 +/- 0.8 mU/l, p <0.001), while
      IGFBP-2 (4.6 +/- 0.5 vs 6.6 +/- 0.7%, p <0.05) and the ratio IGFBP-2/IGF-I (0.032
      +/- 0.019 vs 0.095 +/- 0.01, p = 0.013) were lower than in controls. BMI and
      insulin were directly, and IGFBP-2 serum levels inversely, correlated to total
      GHBP serum levels when multiple regression analysis was performed (r = 0.74, p
      <0.001). By stepwise regression analysis, insulin (r = -0.37, p <0.05) and BMI (r
      = -0.52, p <0.01) inversely determined IGFBP-2. In summary, obese children
      present normal growth in spite of reduced GH secretion, probably because the
      combination of increased total GHBP and normal GH-GHBP complex serum levels
      (suggesting increased GH receptor [GHR] number and a normal serum GH reservoir,
      respectively) allow for the achievement of normal levels of IGF-I, IGFBP-3, IGFBP
      3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Reduced IGFBP-2
      serum levels and a lower ratio of IGFBP-2/IGF-I in obese children may suggest an
      increase of tissue IGF-I bioavailability, thus promoting its action. Normal IGF-I
      and GH availability may be contributing to maintain normal growth in obese
      children.

PMID- 15237711
TI  - Accelerated versus slowly progressive forms of puberty in girls with precocious
      and early puberty. Gonadotropin suppressive effect and final height obtained with
      two different analogs.
AB  - OBJECTIVES: To distinguish which children with precocious puberty (PP) and early
      puberty (EP) should be treated and which followed without therapy. To determine
      the effect of GnRH analog treatment on the final height of treated patients and
      compare the effect of two different analogs on gonadotropin suppression and final
      height. STUDY DESIGN: Sixteen females with PP or EP with a mean chronological age
      (CA) of 8.8 +/- 1.4 years and a mean bone age (BA) of 10.8 +/- 1.3 years were
      treated for a mean of 2.7 +/- 1.0 years with a GnRH analog (triptorelin or
      leuprolide acetate; group A), while 21 girls with a mean CA of 8.5 +/- 1.0 years,
      a mean BA of 9.7 +/- 1.4 years and a predicted adult height of >155 cm were
      followed without therapy (group B). Criteria for treatment were one of: a.
      predicted adult height (PAH) of <155 cm initially or at any time during follow
      up; b. PAH over 155 cm with a dramatic decrease in PAH over a 6-month follow-up
      period; c. advanced and rapidly progressing breast development for age (Tanner 3
      before the age of 9 years). RESULTS: GnRHa therapy suppressed gonadotropins in
      group A, while gonadotropins increased gradually in group B. Height velocity (HV)
      decreased in group A, while it remained accelerated in group B; BA increased a
      mean of 1.7 +/- 0.5 years in group A and 3.2 +/- 0.3 years in group B. This
      resulted in a height increase in group A from a baseline PAH of 153.7 +/- 1.2 cm
      to a final height (FH) of 160.9 +/- 4.0 cm (p <0.001), clearly above their target
      height (TH) of 157.7 +/- 4.2 cm. The height of group B children did not change
      over time (164.1 +/- 4.1 cm before therapy and 166.0 +/- 6.0 cm at FH), both
      above their TH. The mean leuprolide acetate dose utilized in this study decreased
      during treatment, while both the initial and final triptorelin dose remained
      unchanged. Adequate gonadotropin suppression (peak level of LH and FSH of <2 IU/l
      after i.v. GnRH stimulation) was noted with both leuprolide acetate and
      triptorelin, although LH suppression was slightly more pronounced with
      triptorelin. BA advanced 1.8 +/- 0.4 years during leuprolide acetate treatment
      and 1.5 +/- 0.3 years with triptorelin, so that FH increased a mean of 5.5 +/-
      1.3 cm with leuprolide acetate and 8.7 +/- 2.2 cm with triptorelin. CONCLUSIONS:
      PAH of <155 cm before or during therapy, PAH of >155 cm with a dramatic decrease
      in predicted height over a 6-month follow-up period and/or advanced and rapidly
      progressing breast development in girls with PP or EP were useful parameters in
      deciding which patients to treat. GnRHa therapy suppressed gonadotropins, HV and
      bone maturation in children with an accelerated form of PP or EP, resulting in a
      significant height increase. Final height remained stable over time in untreated
      patients. Adequate gonadotropin suppression was noted with both analogs, although
      with the doses of analog used in our study, LH and BA suppression were more
      pronounced with triptorelin, resulting in a larger height gain.

PMID- 15237712
TI  - Anthropometric and endocrine features in girls with isolated premature pubarche
      or non-classical congenital adrenal hyperplasia.
AB  - Clinical and hormonal changes in girls with precocious pubarche, a multifactorial
      entity, have not been thoroughly investigated. OBJECTIVES: To describe
      anthropometric features and bone age in Brazilian girls with precocious pubarche,
      and to compare clinical and hormonal findings for patients with isolated
      precocious pubarche (IPP) or non-classical congenital adrenal hyperplasia (NC
      CAH). PATIENTS AND METHODS: Twenty-eight girls with precocious pubarche were
      consecutively seen at the Child and Pubertal Gynecologic Clinic and the
      Gynecological Endocrinology Unit of Hospital de Clinicas de Porto Alegre.
      Patients with central precocious puberty and pseudopuberty were excluded from the
      study. Diagnostic criteria: NC-CAH: 17-hydroxyprogesterone (17OHP) >12 ng/ml 60
      min after 0.25 mg i.m. ACTH; IPP: hormonal levels compatible with adrenarche and
      normal adrenal function confirmed by ACTH testing. Anthropometric and hormonal
      features and bone age were assessed. RESULTS: Six patients had NC-CAH, and 22
      IPP. NC-CAH frequency was 21.42%. Weight and BMI were above 50th percentile
      except for patients <4 years; 46% of the girls were either overweight or obese.
      Clinical and hormonal features, except for response to ACTH testing, were similar
      in both groups; all patients were in or above the 50th percentile for height.
      Bone age was advanced in 43% of the patients. There was no statistical difference
      between the groups. CONCLUSION: Slight acceleration of height and bone age, one
      of the clinical manifestations of precocious pubarche, is unlikely to be
      progressively severe.

PMID- 15237713
TI  - When should cranial magnetic resonance imaging be used in girls with early sexual
      development?
AB  - OBJECTIVE: To determine whether concise parameters can be established in girls
      who present with signs of early puberty before the age of 8 years, which would
      help to identify those in whom cranial magnetic resonance imaging (MRI) is
      indicated. METHODS: A retrospective chart review was undertaken over a 10-year
      period from 1992-2002. The two requirements for inclusion in this study were
      girls who manifested pubertal changes before the age of 8.0 years and who
      underwent MRI of the brain. The records of 130 female patients with the
      presumptive diagnosis of precocious puberty (PP) were evaluated. Patients'
      medical records were reviewed for histories of any reported focal neurological
      complaint suspicious for intracranial lesions, such as headaches, seizures, or
      visual disturbances, as well as menses and advanced bone age (>2 SD) compared to
      chronological age. Seventy-five patients met these criteria and were divided into
      two groups. Group I consisted of nine patients with abnormal cranial MRI; Group
      II consisted of 66 patients with normal MRI. RESULTS: The patients in each group
      who had one or more of the central nervous system (CNS) signs and symptoms of
      early sexual development that were evaluated were markedly different. In Group I,
      89% (CI 52-99.7%) had positive signs and symptoms that were suspicious for an
      intracranial lesion. In Group II, 94% (CI 85-98%), 63 of 66 girls, had no CNS
      signs or symptoms. CONCLUSION: The use of cranial MRI in the evaluation of girls
      with early sexual development is excessive. Girls with signs of pubertal
      development before age 8 years should be evaluated and followed. Those with
      specific CNS signs and symptoms, menses, and girls with a rapid advance in sexual
      development should undergo cranial MRI. Using this approach, far fewer patients
      in our study would have had cranial MRI.

PMID- 15237714
TI  - Rathke's cleft cyst in two girls with precocious puberty.
AB  - Rathke's cleft cysts arise from remnants of Rathke's pouch and are usually found
      incidentally on MRI or autopsy. In childhood, the most common presenting symptoms
      of Rathke's cleft cysts are endocrine abnormalities, such as reduced growth
      hormone secretion, hyperprolactinemia, or diabetes insipidus. Non-specific
      symptoms, such as headache and visual disturbance, may also occur. Although
      precocious puberty has occasionally been described in association with
      suprasellar lesions, such as hamartomas, arachnoid cysts, and craniopharyngiomas,
      to our knowledge there have been no documented cases secondary to Rathke's cleft
      cysts. We report here two patients, both of whom presented with precocious
      puberty, and were found to have Rathke's cleft cysts.

PMID- 15237715
TI  - Gonadal dysgenesis with a difference.
AB  - We report here an exceptional clinical finding of a 46,XY phenotypic female with
      complete gonadal dysgenesis, but who was found unexpectedly to have absence of
      the uterus and posterior vagina. Extensive review of current and past literature
      failed to confirm other reports of this variant form of complete gonadal
      dysgenesis.

PMID- 15237716
TI  - Phenotypic analysis and growth response to different growth hormone treatment
      schedules in two siblings with an inactivating mutation in the growth hormone
      releasing hormone receptor gene.
AB  - Mutations in the GHRH receptor (GHRHR) gene (GHRHR) are emerging as a common
      cause of familial isolated growth hormone deficiency (IGHD) type IB. The use of
      gonadotropin-releasing hormone (GnRH) analogues has been advocated as a tool to
      delay puberty in patients with isolated GH deficiency (IGHD), allowing longer
      time for the beneficial effect of exogenous human GH (hGH) treatment on growth.
      We describe two male siblings with IGHD due to a homozygous missense GHRHR
      mutation who, because they were started on hGH therapy at different ages,
      presented with different height SDS at the onset of puberty and therefore had
      different predicted target heights. The shorter brother was treated with GnRH
      analogue plus hGH for 3 years, whereas the other brother received only hGH.
      Despite different predicted heights at the onset of puberty, they attained
      similar final heights. We conclude that in patients with IGHD, GnRH analogue
      treatment should be considered to delay puberty and obtain a maximal growth
      response if hGH treatment is started in late childhood and the predicted height
      at puberty onset is below the genetic target.

PMID- 15237717
TI  - Pallister-Hall syndrome with hypoparathyroidism.
AB  - We report on a 5 2/12 year-old boy who presented with convulsions, precocious
      puberty due to a 1.9 x 1.9 x 1.6 hypothalamic hamartoma of the tuber cinereum,
      and some dysmorphic features including polysyndactyly of hands and feet,
      suggesting the diagnosis of Pallister-Hall syndrome. Hypocalcemia due to
      hypoparathyroidism was demonstrated, and this combination has not been reported
      previously. Therefore, we can add hypoparathyroidism as another feature of
      Pallister-Hall syndrome.

PMID- 15237718
TI  - Treatment of adolescents with type 1 diabetes mellitus.

PMID- 15237719
TI  - [AIDS and neurological diseases: epidemiology, etiology and classification].

PMID- 15237720
TI  - [Diagnostic imaging of intracranial lesions in AIDS].

PMID- 15237721
TI  - [HIV associated encephalopathy after highly active antiretroviral therapy
      (HAART)].

PMID- 15237722
TI  - [A new murine model of HIV-associated encephalopathy].

PMID- 15237723
TI  - [Neuromuscular diseases associated with HIV-1 infection].

PMID- 15237725
TI  - [Transient abnormalities associated with status epilepticus on diffusion-weighted
      MR imaging].
AB  - We report on two patients with transient abnormalities on MRI during status
      epilepticus(SE). Diffusion-weighted MR imaging(DWI) and T2-weighted and fluid
      attenuated inversion recovery (FLAIR) MR images showed cortical and thalamic
      hyperintensity with swelling of the cortex. The lesions did not respect vascular
      territories. We also observed an increased signal in the ipsilateral middle
      cerebral artery on magnetic resonance angiography(MRA), and leptomeningeal
      enhancement on postcontrast MRI. Follow-up imaging revealed that the abnormal
      findings resolved within a few weeks, although a residual area of increased T2
      signal intensity persisted. These findings suggest the presence of reversible
      cytotoxic and vasogenic edema induced by seizure. We conclude that this disorder
      should be taken into consideration in the differential diagnosis of other
      conditions, including ischemic stroke.

PMID- 15237724
TI  - [Surgical treatment for temporal lobe epilepsy in patients over age 50 years].
AB  - We retrospectively analyzed 4 patients over age 50 (52 - 57) years with
      intractable medial temporal lobe epilepsy(MTLE) who underwent the anterior
      temporal lobectomy with hippocampectomy. Case 1 had MTLE with old brain abscess
      in the left lateral temporal lobe and Cases 2 - 4 had MTLE with histologically
      verified hippocampal sclerosis. In Cases 2 - 4, although the onset of seizures
      occurred 26 to 37 years prior to the time of surgery, there was no mental problem
      (IQ = 87 - 100). In Cases 1, chronic invasive electrocorticography recording
      using subdural electrodes was obtained, while in Case 2 - 4, the epileptogenic
      region was defined by noninvasive preoperative evaluation. Postoperatively, all
      patients obtained a meaningful improvement, becoming either free from seizures or
      only experiencing a rare seizure, and returned to work or usual activities
      without surgical complications. Surgery for MTLE appears to be effective for
      older individuals and carries a small risk of postoperative complications.

PMID- 15237726
TI  - [Dramatic improvement of urinary retention and the left lower limb paresis with
      methylprednisolone in a case of regional encephalitis following varicella zoster
      infection].
AB  - We report a previously well 14-year-old male who developed left-sided
      hemiconvulsion, urinary retention and hemiplegia 1 months after varicella-zoster
      virus (VZV) infection. Brain T2-weighted MRI showed hyperintensity in medial
      fronto-parietal area including cyngulate gyrus, foot division of the motor
      cortex, para-central lobule and corpus callosum with right predominance, which
      corresponded to hyperperfusion area in SPECT study. MR angiography revealed no
      occlusion or narrowing of vessels. Cerebrospinal fluid (CSF) showed mononuclear
      pleocytosis. After methylprednisolone pulse tharapy under diagnosis of regional
      encephalitis, the patient recovered completely. Although polymerase chain
      reaction(PCR) could not detect VZV-DNA in CSF, antecedent VZV infection might be
      closely related to pathomechanism of the regional encephalitis. Dramatic response
      to steroid, rapid recovery on MRI and good prognosis supported that the
      underlying pathology was mainly vasogenic edema rather than cytotoxic edema.

PMID- 15237727
TI  - [A case with late-onset MELAS with hallucination and delusion].
AB  - We report a 53-year-old male patient with late onset mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes(MELAS) with
      hallucination and delusion. The patient manifested various neurological symptoms
      including perceptive deafness, muscle weakness of limbs with loss of
      consciousness, sensory abnormalities in hands, feet and a face, abnormal sense of
      taste, tremor, palsy of upward eye movement and weak deep tendon reflexes prior
      to the psychotic episode. He was diagnosed as MELAS, because of high serum lactic
      acid and pyruvic acid, and the point mutation in the mitochondrial DNA 3243.
      SPECT imaging showed decreased perfusion in occipital cortex and thalamus. These
      SPECT changes improved after disappearing visual hallucination. Hallucination
      might be caused by delirium due to stroke-like episode. Dysfunction in the
      occipital cortex and thalamus might be involved with this perfusion change.

PMID- 15237728
TI  - [Two cases of Parkinson's disease in which visual hallucinations disappeared
      after cataract surgery].
AB  - We report two cases of Parkinson's disease in which visual hallucinations
      disappeared after cataract surgery. Patient 1 was a 72-year-old woman with
      Parkinson's disease, visual hallucinations and musical hallucinations. Patient 2
      was a 77-year-old woman with Parkinson's disease and visual hallucinations. Both
      patients had severe bilateral cataracts. Though it was difficult to control their
      visual hallucinations with medication only, cataract surgery made them
      disappeared quickly. The visual hallucinations of Parkinson's disease are similar
      to those of Charles Bonnet syndrome. For example, both hallucinations often
      happen in dim light, at night and when patients are awake with eyes open. Though
      there have been many reports describing visual hallucinations in Parkinson's
      disease, there have been few reports discussing the relation between these
      hallucinations and impaired visual acuity. Similar to the hallucinations of
      Charles Bonnet syndrome, impaired visual acuity should be related to the visual
      hallucinations of Parkinson's disease. When Parkinson's disease, visual
      hallucinations and severe cataract coexist, visual hallucinations may disappear
      after cataract surgery.

PMID- 15237729
TI  - [A case of organized chronic subdural hematoma presented with transient
      neurologic deficits].
AB  - A 59-year-old diabetic male presented with transient motor aphasia and
      monoparesis of the right upper limb. Brain CT scan showed a low density area in
      the left subdural space with a mild midline shift. Magnetic resonance (MR) T2
      weighted and fluid-attenuated inversion recovery (FLAIR) imagings revealed
      homogenous hyperintensity with a hypointense web-like structure in the subdural
      hematoma. Cervical MR angiography showed no abnormal lesion at the bifurcation of
      the bilateral common carotid arteries. Conventional cerebral angiography showed
      an avascular, crescent, space-occupying mass over the left hemisphere without an
      etiologic lesion of cerebral ischemia. CT perfusion imagings indicated reduced
      cerebral blood flow (CBF) and prolonged mean transit time (MTT) in the left
      middle cerebral artery territory underneath the subdural hematoma. No epileptic
      discharge was found in electroencephalogram. Operative findings indicated that
      the hematoma was encapsulated with thickened outer and inner membranes including
      paste-like materials, and the brain surface was intact. Postoperative CT
      perfusion imagings revealed normal CBF and MTT. The pathophysiological mechanism
      which the chronic subdural hematoma produces the transient neurological deficit
      is still uncertain. The mechanical pressure of the hematoma on the neighboring
      cerebral vessels may cause impairment of blood flow leading to cerebral ischemia
      and paralysis of function. Our case indicated the transient neurological deficits
      attributed to a decreased CBF around the subdural hematoma and a change in
      pressure exerted by the hematoma during changes of head position and increased
      blood viscosity.

PMID- 15237731
TI  - [MRI findings of hypertensive brainstem encephalopathy].

PMID- 15237730
TI  - [Acute compensation of cerebral blood flow via left posterior cerebral artery in
      cerebral embolism].

PMID- 15237732
TI  - [Clinical features of Parkinson's disease in the elderly].

PMID- 15237733
TI  - [The biological significance of the ubiquitin signaling].

PMID- 15237734
TI  - [Global aging and the tasks of Japan].

PMID- 15237736
TI  - [The contribution of maintaining oral functions to the healthy longevity of the
      elderly].

PMID- 15237735
TI  - [Brain aging and the control of longevity].

PMID- 15237737
TI  - [Anti-dementia drugs--current trend].

PMID- 15237738
TI  - [The evaluation of the public long-term care insurance: from the perspective of
      the service users].

PMID- 15237740
TI  - [Long-term care insurance in Japan and dentistry].

PMID- 15237739
TI  - [The role of geriatrics for disability prevention].

PMID- 15237741
TI  - [The long-term care insurance system and geriatric psychiatry].
AB  - The long-term care insurance system targets people who require support because of
      mental or physical disturbances due to aging. This overlaps in many areas with
      the field of geriatric psychiatry, which is expected to play a significant role
      in diagnosis and hospitalization in the long-term care insurance system.
      Representative of the former is the forgetfulness clinic, and representative of
      the latter is the "senile dementia disorder center". When a person at home or in
      a nursing facility becomes seriously demented or suffers serious physical
      illness, he is generally hospitalized. However, there is an ongoing project which
      allows group homes to care for the seriously demented or physically damaged
      elderly. Under the long-term care insurance system, there are many problems that
      should be dealt with by geriatric psychiatry. One essential issue is the lack of
      basic research on judgment abilities and mental competency, even though users are
      expected to select services and make their own decisions under this system. Once
      there is a social support system for the care-requiring elderly, it is necessary
      to assess the decision-making ability of individual elderly. If this ability is
      sufficiently maintained it should be respected to the utmost. If it is impaired,
      we must have a viewpoint on how to provide care through a social system. A
      consensus has yet to be reached on informed consent for the demented elderly, and
      this issue should be considered with a focus on geriatric psychiatry.

PMID- 15237742
TI  - [Maturity of community through care management].

PMID- 15237743
TI  - [Care insurance and education, practice and research of geriatric medicine].

PMID- 15237744
TI  - [From the standpoint in department of geriatrics in university hospital].
AB  - Because Japanese society has increasing elderly persons and also has a low birth
      rate. Medical treatments and benefits will be severely limited in the future
      because of economic problems. I would like to look back on the history of
      Japanese Geriatrics Society and the many studies on geriatrics in Japan. The
      first annual meeting of Japanese Geriatric Society were held in 1959 and the
      Japanese Gerontology Society meeting was also held in the same year by Geriatric
      Society and Geriatric Sociology Association. It was held every two years, and now
      it consists of 6 associations, that is Geriatrics. Geriatric Sociology. Basic
      Gerontology, Geriatric Dentistry, Geriatric Psychiatry and Care Management
      Associations. I will introduce the activities of these associations, and also
      introduce the contribution of departments of geriatrics in Japanese universities.
      I will also show the system of medical examinations and treatment, the education
      curriculum for medical students and residency, and research composing of various
      theme such as basic gene therapy as well as the evaluation of terminal care for
      the elderly in our Department of Geriatrics, Nagoya University Graduate School of
      Medicine. Finally, I would like to propose future research plan between
      departments of geriatrics in Japanese Universities and the National Institute for
      Longevity Sciences, which will open next March.

PMID- 15237745
TI  - [Health care systems for the aged in Japan and the USA].

PMID- 15237746
TI  - [Present medical care for the elderly and its future prospects].

PMID- 15237747
TI  - [Incidence of adverse drug reactions in geriatric wards of university hospitals].
AB  - Adverse drug reactions (ADR) in elderly people, which have been shown to increase
      with age, are often attributed to functional decline and polypharmacy. A multi
      institutional retrospective survey was undertaken to investigate the current
      status of ADR in geriatric wards of university hospitals. The inpatient database
      from 2000 to 2002 in 5 university hospitals was studied, and a total of 1,289
      patients were analyzed. The incidence of ADR, as determined by attending
      physicians, was 9.2% on the whole but varied from 6.3% to 15.8% among the
      institutions. The factors significantly related to ADR were number of diagnoses,
      number of geriatric syndromes, number of prescribed drugs, increase of more than
      two drugs during admission, longer hospital stay, emergency admission, depression
      and apathy. These results are mostly consistent with previous reports and will
      provide important information on pharmacotherapy in elderly people.

PMID- 15237748
TI  - [Evidence-based medicine of the pharmacological treatment for the elderly:
      Hyperlipemia].

PMID- 15237750
TI  - [Tailor-made medicine and genetic polymorphism: Pneumonia and hypertension].

PMID- 15237749
TI  - [Current therapies in dementia].
AB  - Currently, cholinergic therapies for Alzheimer's disease (AD) have been developed
      and widely accepted based upon an observation that presynaptic cholinergic
      neurons in the basal nucleus of Meynert that widely project to the cerebral
      cortices are consistently damaged in AD brains. Since it is likely that the loss
      of central cholinergic activity may be associated with cognitive worsening in
      patients with AD, it is hypothesized that cholinergic augmentation could improve
      the cognitive ability of patients with AD. Cholinesterase inhibitors represent
      one way of implementing this strategy by inhibiting the breakdown of
      acetylcholine and increasing its availability in synapses. Indeed, several recent
      clinical trials of donepezil, galanthamine and rivastigmine have come to the
      conclusion that these cholinesterase inhibitors have overall beneficial effects
      in cognitive as well as global functions. American Academy of Neurology
      recommended a use of cholinesterase inhibitors as a first choice medicine in the
      treatment of AD. All 3 major studies of Donepezil from USA, Europe and Japan have
      reached the same conclusion favoring Donepezil in the treatment of mild to
      moderate AD. Donepezil can also be used as a safe and efficacious drug in the
      elderly aged 85 or older. Clinical trial of galantamine is in progress in Japan.
      Moreover, herbal medicines named kami-untan-to and hachimi-jiou-gan have been
      shown to be beneficial in some priority studies with a small sample size. It is
      critically needed to widen therapeutic windows in the treatment of AD.

PMID- 15237751
TI  - [Perspectives for tailor-made medicine for osteoporosis].

PMID- 15237752
TI  - [A randomized controlled trial of a treadmill training with the perturbation to
      improve the balance performance in the community dwelling elderly subjects].
AB  - We had developed a gait perturbation system based on a treadmill composed of two
      separate walking belts. The servomotors in this treadmill are controlled by a
      personal computer. A falling perturbation can be generated by the sudden and
      random deceleration of the walking belts. The purpose of this study was to
      determine, in a cohort of community dwelling elderly subjects, whether our
      treadmill training with the perturbation would improve balance performance. The
      29 participants aged over 65 years were randomly assigned to receive either
      perturbed treadmill training or ordinary treadmill training. The single leg
      standing time with the eyes opened and closed, the functional reach test (FR),
      the timed up and go test (TUG), the 10 m maximum gait speed and the latency of
      the bilateral tibialis anterior muscle (LTA) were measured at the pre training
      period and after the 4-week training period. These indexes were measured again
      one month after the training period. There were no significant differences
      between the perturbed training subjects and the ordinary training subjects in
      these indexes in the pre-training period. Following training period, the
      perturbed training subjects were improved in FR (mean +/- SD: pre 30.3 +/- 5.0
      cm, post 33.5 +/- 5.0 cm, p<.01). TUG (mean +/- SD; pre 5.13 +/- .68 sec, post
      4.86 +/- .53 sec, p<.05) and LTA (the perturbed side, mean +/- SD; pre 134 +/- 30
      msec, post 116 +/- 22 msec, p<.01, the non-perturbed side, mean SD:pre 132 +/- 35
      msec, post 114 +/- 27 msec, p <.05). On the other hand, the ordinary training
      subjects were improved only in TUG (mean +/- SD; pre 4.93 +/- . 52 sec, post 4.60
      +/- .39 sec. p<.01). Additionally, the improvements of the LTA on the perturbed
      training subjects were retained one month after the training period (the
      perturbed side, mean +/- SD: pre 134 +/- 30 msec, after 1-month 117 +/- 19 msec,
      p<.01, the non-perturbed side, mean +/- SD: pre 132 +/- 35 msec, after 1-month
      115 +/- 24 msec, p<.05). The improvements of LTA may represent the improvements
      of the ability of the stepping reaction which is one of the important factors to
      avoid the falling. Our treadmill training with perturbation improves the balance
      performance and may decrease the risk of falling in the community dwelling
      elderly subjects.

PMID- 15237753
TI  - [Adiponectin levels and coronary risk factors in the elderly].
AB  - AIM: To determine the relationship between adiponectin level and coronary risk
      factors in men. METHODS: The subjects were 395 elderly men in two rural
      communities (Tanno, Sobetsu) in Japan. Blood pressure in the sitting position
      (SBP/DBP), after overnight fasting, plasma glucose level (FPG), total cholesterol
      (TC), triglyceride (TG), HDL cholesterol (HDL) and serum adiponectin were
      measured. The subjects were divided into two adiponectin level groups, a high
      adiponectin level (> or = 7.94 microg/ml) group (H-Adipo group) and a normal
      adiponectin level (< 7.94 microg/ml) group (N-Adipo group), and into two age
      groups, 70 years of age or older (70 or older group) and less than 70 years of
      age (under 70 group). RESULTS: Adiponectin showed negative correlations with BMI,
      FPG, TC and TG and positive correlations with age, SBP and HDL. In multiple
      regression analysis using adiponectin as a dependent variable. BMI, SBP, FPG, TG
      and HDL were selected as independent variables. Age and HDL in the H-Adipo group
      were significantly higher than those in the N-Adipo group, and BMI, FPG, TC and
      TG in the H-Adipo group were significantly lower than those in the N-Adipo group.
      In the 70 or older group. SBP and adiponectin were significantly higher and BMI,
      DBP, FPG, TC and TG were significantly lower than those in the under 70 group.
      The mean number of total coronary risk factors in the 70 or older group (1.71)
      was significantly lower than that in the under 70 group (2.06). CONCLUSIONS:
      Coronary risk factors other than systolic blood pressure were significantly
      reduced in the older subjects.

PMID- 15237754
TI  - [An elderly case of acute myelocytic leukemia complicated with bleeding gastric
      angiodysplasia, successfully treated with topical endoscopic polidocanol
      injection].
AB  - A 72-year-old man with acute myelocytic leukemia (AML) suffered relapsing massive
      bleeding from gastric angiodysplasia. He was referred to our hospital in February
      2000 because of anemia and thrombocytopenia. He had hypercellular (nucleated cell
      count 42 x 10(4)/microl) bone marrow with 90% myeloblasts, and AML (FAB: M1) was
      diagnosed. Remission induction therapy by BHAC/DM regimen failed. While
      considering subsequent regimens, massive hematemesis from a solitary gastric
      angiodysplasia developed. In April, after re-remission induction by CAG regimen,
      hematemesis from the same lesion reccurred. Hemostasis was achieved by topical
      transendoscopic injection of polidocanol. After achievement of complete remission
      by CAG therapy, he was treated on an outpatient basis. In July, his AML relapsed
      and he was treated mainly by transfusion therapy. In September, hematemesis
      recurred resulting in hemostasis with the same procedure. In the course of
      endoscopic injections, his mucosal lesion became difficult to observe. Gastric
      angiodysplasia is occasionally observed in the elderly, but massive bleeding is a
      rare complication. In this case, topical injection of polidocanol was an
      effective procedure for the massive bleeding from it even in an elderly patient
      with the complication of thrombocytopenia due to AML.

PMID- 15237755
TI  - [A patient with von Recklinghausen's disease associated with polymyositis,
      asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma].
AB  - A 72-year-old woman with von Recklinghausen's disease was referred to our
      hospital because of pain and muscle weakness in her thighs. She had elevated
      serum values of creatine kinase, aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a
      diagnosis of polymyositis was made. Treatment with prednisolone improved muscle
      strength, and laboratory values returned to normal. Computed tomography, magnetic
      resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG
      scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left
      adrenal gland. Endocrinologic investigation disclosed elevation of serum and
      urine catecholamines. Since the blood pressure was normal, nonfunctioning
      pheochromocytoma was diagnosed clinically. The nonhypertensive course was
      attributed to reduced vascular response to noradrenaline. Serum lactate
      dehydrogenase. alkaline phosphatase. and asparate aminotransferase became
      elevated, and abdominal computed tomography showed a well-defined mass measuring
      13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right
      trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a
      typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of
      elongated spindle-shaped atypical cells arranged in intersecting bundles.
      Immunohistochemically, the cells of this tumor were reactive for alpha-smooth
      muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the
      liver. Eight months after onset of symptom, the patient developed hepatic coma
      and died. The mean age at presentation with pheochromocytoma in von
      Recklinghausen's disease patients age is 42 years. Our patient was considerably
      older. To the best of our knowledge this is the first report of a patient with
      von Recklinghausen's disease developing polymyositis. asymptomatic
      pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to
      remain aware of the possibility of cancer in von Recklinghausen's disease.

PMID- 15237756
TI  - Vespula.

PMID- 15237757
TI  - Ideals for the allergist: the importance of teaching in allergy.

PMID- 15237758
TI  - The skin prick test: "more than meets the eye".

PMID- 15237759
TI  - Clinical implications of airway inflammation in mild intermittent asthma.
AB  - OBJECTIVE: To determine whether inhaled corticosteroids should be prescribed to
      patients with milder forms of asthma and whether markers of airway inflammation
      should be considered when making therapy decisions. DATA SOURCES: A PubMed search
      was performed of the English-language literature published in the preceding 10
      years (January 1, 1993, through December 31, 2003) concerning epidemiology,
      pathophysiology, therapy, and prognosis of mild intermittent asthma, with asthma,
      mild, and intermittent as indexing terms. STUDY SELECTION: All relevant studies
      including author's expert opinions were selected. RESULTS: Several studies have
      addressed the question of a possible benefit of maintenance therapy (ie, inhaled
      steroids) in patients with mild intermittent asthma. Although a diminishing
      effect on airway inflammation has been widely demonstrated, even in patients with
      mild disease, the impact of inhaled steroids on the long-term prognosis is much
      less clear. For patients with mild disease who are long-term inhaled steroid
      users, alternative therapy strategies, including low-dose inhaled steroids and
      leukotriene receptor antagonists, have been advocated. CONCLUSIONS: Mild
      intermittent asthma is a disease characterized not only by infrequent symptoms
      and normal lung function but also by chronic airway inflammation, possibly
      resulting in irreversible airflow limitation if left unattended. Therefore,
      maintenance therapy, such as (low-dose) inhaled steroids or leukotriene receptor
      antagonists, should be considered in patients with mild disease. Future studies
      should give more insight into the impact of prolonged anti-inflammatory therapy
      on the long-term prognosis of mild intermittent asthma patients. Whether results
      from these studies will justify a more aggressive treatment for these patients
      remains to be answered.

PMID- 15237760
TI  - Eosinophilia in an Iranian woman.

PMID- 15237761
TI  - Optimal skin prick wheal size for diagnosis of cat allergy.
AB  - BACKGROUND: The skin prick test is the diagnostic procedure of choice for
      determination of immediate hypersensitivity. A wheal diameter of 3 mm or larger
      is generally accepted as the cutoff for a positive test result, although the
      validity of this assumption has not been rigorously demonstrated. OBJECTIVE: To
      determine the skin prick wheal size that best identifies clinical allergy to cat.
      METHODS: Forty-five patients referred for evaluation of rhinoconjunctivitis
      underwent determination of atopic status by skin testing using the Greer Dermapik
      device and a combination of other modalities, including history, in vitro
      determination of specific IgE level, and nasal challenge with standardized cat
      pelt extract. Parameters evaluated before and after nasal challenge included
      symptom score and nasal lavage tryptase and prostaglandin D (PGD2) levels.
      RESULTS: The widely accepted 3-mm wheal for a positive skin test result to cat is
      highly sensitive but only moderately specific for diagnosis of cat allergy as
      evaluated by history, specific IgE level, postchallenge symptom score, and
      tryptase and PGD2 levels. Optimal cutoffs for a positive skin test result to cat
      based on receiver operating characteristic analysis and 95% positive predictive
      value were 5.5 mm or greater for each of these parameters. When a true-positive
      result for cat allergy was defined as a combination of positive history, specific
      IgE level, postchallenge symptom score, and tryptase and PGD2 levels and a true
      negative result as all of these parameters being negative, a 6-mm cutoff was able
      to distinguish cat allergic from cat nonallergic individuals. CONCLUSION: In a
      potentially allergic population undergoing skin prick testing with the Greer
      Dermapik using standardized extracts, a 3-mm skin prick wheal will overestimate
      the presence of cat allergy. A 6-mm wheal appears to distinguish those
      individuals who are cat allergic from those who are not.

PMID- 15237763
TI  - Anaphylaxis during surgical and interventional procedures.
AB  - OBJECTIVE: To describe the current evidence-based knowledge of the causes,
      diagnostic evaluation, and treatment of patients with anaphylaxis associated with
      surgical and interventional procedures. DATA SOURCES: Articles published between
      1966 and 2003 were identified in MEDLINE using the keywords anaphylactoid,
      anaphylaxis, anesthetics, antibiotics, cephalosporins, contrast media, colloids,
      flow cytometry, hypersensitivity, latex, neuromuscular depolarizing agents,
      neuromuscular nondepolarizing agents, penicillins, radioallergosorbent test, skin
      test, and vancomycin. Additional studies were identified from article reference
      lists. STUDY SELECTION: Relevant, peer-reviewed original research articles and
      reviews. RESULTS: Neuromuscular blocking agents, natural rubber latex,
      antibiotics, and induction agents are the most common causes of anaphylaxis
      during surgical and interventional procedures. Colloids, opioids, and
      radiocontrast media probably account for less than 10% of all reactions. Newer
      agents implicated in anaphylaxis include isosulphan blue and chlorhexidine. Skin
      tests are useful for evaluating allergic reactions to anesthetic agents and
      penicillins and for selecting alternative agents. Skin testing and specific IgE
      measurements for latex vary in allergen standardization and sensitivity and
      specificity, respectively. Flow cytometric allergen stimulation tests show
      promise in differentiating allergic from idiosyncratic ("pseudoallergic")
      reactions. Drug desensitization has been shown to be useful for penicillin
      anaphylaxis. Premedication with histamine receptor antagonists and
      corticosteroids helps prevent or attenuate radiocontrast media reactions.
      CONCLUSIONS: Anaphylaxis during surgical and interventional procedures may be
      difficult to evaluate because of the rapid, successive use of multiple drugs or
      diagnostic agents. Careful analysis of anesthetic records and diagnostic tests
      for all the putative agents are necessary to ensure a complete evaluation.

PMID- 15237762
TI  - Effectiveness of a multicomponent self-management program in at-risk, school-aged
      children with asthma.
AB  - BACKGROUND: Improving asthma knowledge and self-management is a common focus of
      asthma educational programs, but most programs have had little influence on
      morbidity outcomes. We developed a novel multiple-component intervention that
      included the use of an asthma education video game intended to promote adoption
      of asthma self-management behaviors and appropriate asthma care. OBJECTIVE: To
      determine the effectiveness of an asthma education video game in reducing
      morbidity among high-risk, school-aged children with asthma. METHODS: We enrolled
      119 children aged 5 to 12 years from low-income, urban areas in and around San
      Francisco, CA, and San Jose, CA. Children with moderate-to-severe asthma and
      parental reports of significant asthma health care utilization were randomized to
      participate in the disease management intervention or to receive their usual care
      (control group). Patients were evaluated for clinical and quality-of-life
      outcomes at weeks 8, 32, and 52 of the study. RESULTS: Compared with controls,
      the intervention group had significant improvements in the physical domain (P =
      .04 and P = .01 at 32 and 52 weeks, respectively) and social activity domain (P =
      .02 and P = .05 at 32 and 52 weeks, respectively) of asthma quality of life on
      the Child Health Survey for Asthma and child (P = .02 at 8 weeks) and parent (P =
      .04 and .004 at 32 and 52 weeks, respectively) asthma self-management knowledge.
      There were no significant differences between groups on clinical outcome
      variables. CONCLUSIONS: A multicomponent educational, behavioral, and medical
      intervention targeted at high-risk, inner-city children with asthma can improve
      asthma knowledge and quality of life.

PMID- 15237764
TI  - Atmospheric pollution and the prevalence of asthma: study among schoolchildren of
      2 areas in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Air pollutants have been associated with the exacerbation of
      respiratory diseases. They may intensify the inflammatory allergic response and
      airways reactivity to inhaled allergens. However, it is still not clear if air
      pollution contributes to the increased prevalence of asthma. OBJECTIVE: To
      investigate if different levels of air pollution exposure can be related to
      differences in the prevalence of asthma. METHODS: The International Study of
      Asthma and Allergies in Childhood (ISAAC) protocol was used to determine and
      compare the prevalence of asthma among schoolchildren in 2 cities of the
      metropolitan region of Rio de Janeiro, Brazil, Duque de Caxias (DC) and
      Seropedica (SR), which have different levels of atmospheric pollution. The
      research involved 4,064 students aged 13 to 14 years from 49 schools in DC and
      1,129 from 17 schools in SR. Air pollution was evaluated by the concentration of
      inhalable particulate matter (PM10). RESULTS: ISAAC's written questionnaire was
      answered by 4,040 students aged 13 to 14 years in DC and 1,080 in SR. Between
      1998 and 2000, the PM10 annual arithmetic mean was 124 microg/m3 in DC and 35
      microg/m3 in SR (acceptable level is up to 50 microg/m3). The prevalence of
      wheezing ever was 35.1% in DC and 29.9% in SR (P = .001), and the prevalence of
      wheezing in the last 12 months was 19.0% in DC and 15.0% in SR (P = .002). In DC,
      14.5% of the adolescents presented 1 to 3 crises of wheezing in the last year,
      whereas in SR only 11.0% presented 1 to 3 crises (P = .003). CONCLUSIONS: In this
      study, the prevalence of asthma in adolescents was directly related to
      atmospheric pollution.

PMID- 15237765
TI  - Comparative activity of cetirizine and desloratadine on histamine-induced wheal
      and-flare responses during 24 hours.
AB  - BACKGROUND: Cetirizine and desloratadine are antihistamines active in the
      treatment of symptoms associated with seasonal allergic rhinitis and chronic
      urticaria. OBJECTIVE: To compare the antihistamine activity of desloratadine, the
      active metabolite of loratadine, with that of cetirizine in the skin wheal-and
      flare responses during 24 hours. METHODS: This was a double-blind, randomized,
      placebo-controlled, single oral dose, crossover study. Skin reaction to histamine
      (100 mg/mL), administered by prick tests, was measured by the wheal and flare
      surface areas for 24 hours (before treatment and at 0.5, 1, 2, 3, 4, 6, 8, 10,
      12, and 24 hours). Eighteen healthy volunteers (mean age, 33.9 years; 13 women)
      participated in this study. The areas under the curves of the wheal-and-flare
      responses as a function of time (primary efficacy variables) were compared using
      analysis of variance. RESULTS: A highly significant overall treatment effect (P <
      .001) was detected for wheal and flare inhibition, with the activity of
      cetirizine and desloratadine significantly superior to that of placebo (P <
      .001). In addition, the activity of cetirizine was significantly superior to that
      of desloratadine (P < .001). With desloratadine, only 3 of the 18 subjects
      achieved a wheal inhibition of at least 70%, occurring between 2 and 4 hours,
      whereas all subjects using cetirizine reached a wheal inhibition of at least 70%
      between 0.5 and 3 hours (median time, 1.7 hours). The difference between the 2
      active drugs was highly significant (P < .001). The median duration of wheal
      inhibition of at least 70% was zero with placebo and desloratadine and was 21.9
      hours with cetirizine (P < .001). No serious adverse events were reported, and no
      subject withdrew from the study due to an adverse event. CONCLUSION: Cetirizine
      was associated with significantly greater suppression of skin reactivity to
      histamine compared with desloratadine during 24 hours after a single dose, with a
      consistent duration of action for cetirizine, as previously reported.

PMID- 15237766
TI  - Addition of montelukast or salmeterol to fluticasone for protection against
      asthma attacks: a randomized, double-blind, multicenter study.
AB  - BACKGROUND: For patients whose asthma is uncontrolled with low-dose inhaled
      corticosteroids, addition of alternative therapy instead of increasing the
      steroid dose is recommended by current treatment guidelines. OBJECTIVE: To
      compare montelukast, a once-daily leukotriene receptor antagonist, and
      salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered
      with inhaled fluticasone, according to the percentage of patients without an
      asthma attack for 1 year. METHODS: A randomized, double-blind, double-dummy,
      multicenter study was conducted. Adult patients with moderate-to-severe
      persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 microg/d)
      who remained symptomatic during a 4-week run-in period were randomized to the
      addition of salmeterol (84 microg/d) or montelukast (10 mg/d) for 48 weeks.
      RESULTS: Of the 1,473 randomized patients, 743 were randomized to montelukast and
      730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients
      in the montelukast group and 83.3% of patients in the salmeterol group remained
      attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence
      interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts
      compared with salmeterol, whereas salmeterol significantly increased prealbuterol
      forced expiratory volume in 1 second, asthma-specific quality of life, morning
      peak expiratory flow rate, and decreased nocturnal awakenings compared with
      montelukast. Differences between treatments were small, and both treatments were
      generally well tolerated. CONCLUSIONS: Addition of montelukast or salmeterol to
      an inhaled corticosteroid similarly protected most patients from experiencing an
      asthma attack during a 1-year period, but, based on noninferiority limits, the
      study was inconclusive with regard to a difference between treatment groups.

PMID- 15237767
TI  - Effect of vitamin E supplementation on the regular treatment of seasonal allergic
      rhinitis.
AB  - BACKGROUND: Vitamin E supplementation is widely used in clinical practice for the
      prevention and treatment of different medical conditions. Evidence from basic
      science studies suggests that vitamin E may reduce immune allergic responses.
      However, only a few clinical studies of the effect of vitamin E on allergic
      conditions have been performed in patients with atopic dermatitis and asthma, and
      none have been performed in patients with allergic rhinitis. OBJECTIVE: To
      determine the effect of high-dose vitamin E supplementation in combination with
      the usual ("real-life") treatment on the symptoms of seasonal allergic rhinitis
      during the pollen season. METHODS: In a double-blind, placebo-controlled,
      randomized study, 112 patients with documented hay fever received either vitamin
      E (800 mg/d) or placebo in addition to their regular antiallergic treatment
      during the pollen season. Patients recorded their daily nasal and eye symptoms
      and their daily need for other medications to control allergic symptoms. RESULTS:
      Although no effect was observed on ocular symptoms, nasal symptom scores were
      lower in patients who received vitamin E supplementation during the hay fever
      season. However, there was no reduction in the percentage of days with serious
      symptoms or in the percentage of days that medications were used to control
      allergic symptoms during the pollen season. CONCLUSIONS: Vitamin E
      supplementation may be a valuable addition to the treatment of patients with
      seasonal allergic rhinitis. However, further clinical and basic science studies
      are needed to determine its real value.

PMID- 15237768
TI  - Discrepancy between cytokine production from peripheral blood mononuclear cells
      and nasal secretions among infants with acute bronchiolitis.
AB  - BACKGROUND: Many studies have measured cytokine production derived from
      peripheral blood mononuclear cells (PBMCs) to evaluate the immune response in
      acute bronchiolitis (AB), but no previous reports have examined the association
      between PBMC release of cytokines and concomitant airway immune response.
      OBJECTIVE: To determine whether interferon-gamma (IFN-gamma), interleukin 4 (IL
      4), and IL-10 levels from PBMCs are associated with concurrent cytokine release
      in the airways of infants with AB. METHODS: Infants with acute viral-associated
      first episode of wheezing who required hospitalization between May and September
      2002 were recruited. Nasopharyngeal aspirates (NPAs) and PBMC samples were
      collected simultaneously. The concentrations of IFN-gamma, IL-4, and IL-10 in NPA
      and PBMC supernatants were determined by enzyme-linked immunosorbent assay.
      RESULTS: Twenty infants with AB were enrolled in the study of whom 17 (85%) had
      positive NPA immunofluorescence results for viral detection and respiratory
      syncytial virus. Median total cell count and viability from NPA samples were 2.2
      x 10(6) cells/mL (SD, 1.7 cells/mL) and 92% (SD, 6.0%), respectively. There was a
      significant correlation between IL-4 levels from NPA and PBMC samples (r = 0.5, P
      = .02); however, we did not find an association between IFN-gamma and IL-10
      levels. CONCLUSIONS: Cytokines produced by in vitro PBMCs may not necessarily
      reflect the concurrent cytokine pattern production at the mucosal surface in the
      respiratory tract of infants with AB. Further studies are required to determine
      whether peripheral blood is a reliable sample for airway inflammation evaluation
      and to explain the discrepancies of cytokine productions found in this study.

PMID- 15237769
TI  - Allergic rhinitis in children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Both allergic rhinitis and attention-deficit/hyperactivity disorder
      (ADHD) are common pediatric conditions associated with learning difficulties and
      sleep disturbances. There are conflicting research data regarding the association
      between ADHD and atopic disorders. OBJECTIVE: To determine the prevalence of
      allergic rhinitis in patients with physician-diagnosed ADHD. METHODS: Patients 5
      to 18 years of age who presented with a Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition diagnosis of ADHD to an outpatient pediatric
      psychiatry clinic were screened for allergic rhinitis with focused history,
      physical examination, and skin prick testing to common aeroallergens. RESULTS:
      Thirty patients were interviewed, with 23 of these undergoing physical
      examination and skin prick testing. Eighty percent reported allergic rhinitis
      symptoms, whereas 61% had at least 1 positive prick skin test result. Forty-three
      percent showed typical physical signs of allergic rhinitis, 100% had a positive
      atopic family history, and 53% had other associated atopic disorders.
      CONCLUSIONS: Most children with ADHD displayed symptoms and skin prick test
      results consistent with allergic rhinitis. Nasal obstruction and other symptoms
      of allergic rhinitis could explain some of the cognitive patterns observed in
      ADHD, which might result from sleep disturbance known to occur with allergic
      rhinitis. Therefore, evaluation and treatment of allergic rhinitis could benefit
      patients with ADHD.

PMID- 15237770
TI  - Effectiveness of immunotherapy for recurring sinusitis associated with allergic
      rhinitis as assessed by the Sinusitis Outcomes Questionnaire.
AB  - BACKGROUND: Outcomes measurement is a proficient method for determining the
      effectiveness of medical therapy. Currently, there are no easy-to-use and
      inexpensive questionnaires available to evaluate the impact of immunotherapy in
      the treatment of sinusitis by allergists, given the research constraints of a
      private practice setting. OBJECTIVE: To measure the effectiveness of
      immunotherapy in the overall treatment of atopic patients with associated
      sinusitis in a private practice setting. METHODS: A total of 114 patients with a
      history of rhinitis and sinusitis and positive radiographic evidence of sinus
      disease were consecutively chosen from 3 private practices nationwide and
      surveyed for global symptoms and specific symptoms related to the nose, sinuses,
      eyes, and chest with the Sinusitis Outcomes Questionnaire (SOQ). Their medical
      history, including prior treatment, was evaluated. This questionnaire was
      administered twice in one sitting, with the first a recall of symptoms before
      starting immunotherapy and the second an evaluation of current symptoms. RESULTS:
      The data revealed that 99% believed immunotherapy worked, with 1% unsure.
      Patients experienced a 72% decrease in days lost from work or school and a 26%
      reduction in the use of medications per year. There was a mean reduction of 51%
      in the overall symptom score of the patients after receiving immunotherapy.
      CONCLUSIONS: This study demonstrates that the user-friendly SOQ can be
      effectively and inexpensively used in a private practice setting and suggests
      that immunotherapy is an effective treatment for patients with sinus disease and
      allergic rhinitis.

PMID- 15237771
TI  - Anaphylaxis to wheat beer.
AB  - BACKGROUND: Despite its worldwide and abundant consumption, beer has rarely been
      found to cause anaphylaxis. Barley malt contained in lager beers seems to be an
      important elicitor. OBJECTIVE: To report the unusual case of severe anaphylaxis
      following the ingestion of wheat beer. METHODS: A 59-year-old man experienced
      angioedema, generalized urticaria, and unconsciousness after ingestion of wheat
      beer. He tolerated lager beer well. For diagnostic evaluation, skin prick tests,
      oral challenge tests, and identification of specific IgE antibodies were
      performed. RESULTS: Skin prick test results with standard series of common
      aeroallergens and food allergens were negative with the exception of a 1 +
      reaction to wheat flour. The results of skin prick tests with native materials
      were positive for 2 brands of wheat beer and wheat malt shred but negative for
      baker's yeast, hops, and a brand of lager beer. Oral challenges with wheat beer
      or wheat flour elicited urticaria. By CAP-FEIA, specific IgE antibodies to wheat
      and barley flour but not to hops or baker's yeast were found in serum. Immunoblot
      analysis revealed that patient's IgE was bound to a protein of approximately 35
      kDa in wheat extract. CONCLUSIONS: This is the first report, to our knowledge, on
      anaphylaxis to beer attributable to wheat allergy.

PMID- 15237772
TI  - Can you top this? 37-year survival of patient with Churg-Strauss syndrome.

PMID- 15237773
TI  - Continuing professional development. Evidence-based radiology problems.
      Transrectal drainage of pelvic abscess: June 2004 - May 2005.

PMID- 15237774
TI  - Patient navigation: improving timeliness in the diagnosis of breast
      abnormalities.
AB  - OBJECTIVE: Patient navigation is a process that provides assistance to referring
      physicians in arranging further investigations and consultation for defined
      patient groups. This can facilitate timely investigations and potentially
      minimize delays. The purpose of this study was to determine the impact of patient
      navigation on timeliness in the diagnosis of breast abnormalities. METHODS: We
      retrospectively studied a cohort of 536 women who underwent breast core biopsy at
      our institution during comparable 6-month periods in 1999 and 2000 to determine
      the effects of patient navigation, age, and biopsy result on the wait for a
      biopsy after diagnostic imaging. Patient navigation was used for all women
      referred through the provincial breast cancer screening program. Navigation was
      unavailable to patients directly referred by physicians in 1999. In 2000, the
      program was expanded to encompass all patients. RESULTS: From 1999 to 2000, the
      median wait for a biopsy remained relatively stable for "navigated" screening
      patients at 12 days (n = 97) and 13 days (n = 133), respectively. The
      introduction of patient navigation for directly referred patients resulted in a
      statistically significant decrease in waiting times, from 20 days (n = 144) in
      1999 to 14 days (n = 162) in 2000. Age and biopsy results were statistically
      significant variables, but their effect on the group data was negligible relative
      to that of navigation. CONCLUSIONS: Patient navigation significantly improves
      timeliness in the diagnosis of breast abnormalities and can potentially improve
      quality of life with more timely reassurance for women with benign conditions and
      earlier treatment for those with malignancy.

PMID- 15237775
TI  - Ultrasonographic findings 6 months after 11-gauge vacuum-assisted large-core
      breast biopsy.
AB  - OBJECTIVE: To assess the ultrasonographic features of post-biopsy change 6 months
      after 11-gauge vacuum-assisted large-core breast biopsy of pathologically proven
      benign lesions. Using the literature as a reference, we hypothesized that large
      core breast biopsy would result in tissue changes that may mimic malignancy and
      may be more apparent on ultrasonography than on mammography. METHODS: Two
      radiologists whose subspecialty is breast imaging retrospectively reviewed the
      pre-biopsy and 6-month follow-up sonograms of 24 patients with pathologically
      proven benign lesions. The images were assessed for the number and type of
      ultrasonographic features. A Breast Imaging Reporting and Data System (BI-RADS)
      category was assigned to each lesion before biopsy and at 6-month follow-up. The
      composition of breast tissue surrounding the lesion was assessed as fatty, mixed
      fibroglandular or dense. RESULTS: The frequency of ultrasonographic changes at 6
      months after 11-gauge vacuum-assisted large-core breast biopsy was more frequent
      than the rate of post-biopsy change previously reported to occur
      mammographically. The nature of these changes may mimic malignancy in some cases.
      CONCLUSION: The ultrasonographic appearance of the breast after large-core breast
      biopsy may mimic malignancy and is, therefore, a potential pitfall when
      interpreting a post-biopsy sonogram.

PMID- 15237776
TI  - Trauma-induced omental herniation simulating pleural effusion: case report.

PMID- 15237777
TI  - Active extravasation of arterial contrast agent on post-traumatic abdominal
      computed tomography.
AB  - OBJECTIVE: To evaluate the use of emergent dynamic intravenous contrast-enhanced
      computed tomography (CT) in the diagnosis of active arterial extravasation in
      patients admitted to hospital after blunt abdominal trauma. METHODS: Four-hundred
      and ninety-eight consecutive emergent contrast-enhanced computed tomographic
      images of the abdomen and pelvis were retrospectively reviewed. The presence of
      and site(s) of active arterial extravasation were recorded. Two radiologists
      reviewed the images and compared the site(s) of extravasated arterial contrast
      agent with the site(s) of active hemorrhage established at angiography (n = 9) or
      surgery (n = 4). RESULTS: Twenty-eight patients' computed tomographic images were
      identified as showing signs of extravasation of contrast agent representing
      active arterial bleeding. A total of 49 sources of active arterial extravasation
      were identified, 37 in 19 patients. A pelvic source of active arterial hemorrhage
      was most frequent and was typically associated with unstable pelvic fractures (n
      = 18). Other sources of active arterial hemorrhage included the liver (n = 3),
      spleen (n = 2), retroperitoneum (n = 1), kidney (n = 1), mesentery (n = 1),
      abdominal wall (n = 3) and lumbar region (n = 1). Only 9 of 28 patients became
      sufficiently hemodynamically unstable to warrant angiography. All 9 patients had
      a pelvic source of arterial extravasation on contrast-enhanced CT, and 7
      demonstrated active bleeding requiring embolization. The contrast-enhanced
      computed tomographic images correctly indicated the anatomical source of bleeding
      in all 7 cases. CONCLUSION: In patients who have experienced blunt abdominal
      trauma, attention should be paid to the computed tomographic features of active
      arterial hemorrhage. In our series, the pelvis was the most common source of
      active arterial bleeding, which was typically associated with unstable pelvic
      fractures.

PMID- 15237778
TI  - The accuracy of references in manuscripts submitted for publication.
AB  - OBJECTIVE: To analyze the errors present in references cited in papers submitted
      for peer review for possible publication. METHODS: Nineteen consecutive
      manuscripts submitted for peer review were assessed. They contained a total of
      261 references. Manuscripts were submitted to 1 of 5 major radiology journals.
      Journal references were compared with either the original articles or abstracts
      obtained through MEDLINE. Book references were checked against the original book.
      In total, 259 of 261 references were obtained. The remaining 2 references were
      both out-of-print books that were not available. Each reference was checked and
      errors were identified as either major or minor, depending on the gravity of the
      error. Errors were analyzed to see whether they could be attributed to not
      adhering to journal guidelines or to other reasons. RESULTS: Of a total of 259
      references, 56% (n = 145) contained at least 1 error, 53% (n = 137) contained
      minor errors and 15% (n = 39) contained major errors. Five per cent (n = 13) of
      references had more than 3 errors, and 79% (n = 274) of all errors were the
      direct result of authors not following journal instructions. CONCLUSION: Over
      half of all references included in manuscripts submitted to radiology journals
      contain at least 1 error. The majority are avoidable, resulting from failure to
      follow the journal's instructions to authors.

PMID- 15237779
TI  - The use of cross-sectional diagnostic imaging in a major Canadian health care
      centre.
AB  - OBJECTIVE: To assess current patterns of use of cross-sectional imaging at 5
      large Canadian teaching hospitals and a cancer centre, in order to better predict
      future use. METHODS: We prospectively reviewed all requisitions for diagnostic
      imaging during a 2-week period in January 2002. Each requisition was assessed by
      means of a form on which the attending radiologist answered 6 questions about the
      appropriateness and usefulness of the requested examination. RESULTS: A total of
      2374 examinations were audited: 1167 ultrasonography, 925 computed tomography and
      282 magnetic resonance imaging examinations. Forms with scores of 3 out of 7 or
      more for the appropriateness and relevance of the imaging request (n = 2229) were
      not examined further. After review of the remaining complete forms, 59 (2.5%)
      were found to contain at least 1 score that was less than 3 out of 7, which was
      considered to be a failing grade. CONCLUSION: There is a low incidence of
      inappropriate use of diagnostic imaging. Practical ways to reduce unnecessary use
      would include close attention to the wasteful practice of test duplication and to
      the need for patient education to help minimize unnecessary testing.

PMID- 15237780
TI  - The clinical meaning of gastric-wall hyperactivity observed on sestamibi cardiac
      single-photon emission computed tomography.
AB  - OBJECTIVE: To evaluate prospectively the incidence and clinical meaning, if any,
      of gastric-wall hyperactivity observed on sestamibi cardiac single-photon
      emission computed tomography (SPECT). This phenomenon is completely different
      from the well-known intraluminal gastric reflux of sestamibi. METHODS: A group of
      819 patients who underwent sestamibi cardiac SPECT was studied from January 2000
      to October 2000. Gastric-wall activity was graded qualitatively. Only patients
      with gastric-wall activity near or equivalent to their heart activity were
      considered for subsequent analysis. The medical records of patient candidates
      were reviewed, and their family physicians were asked to respond to a
      questionnaire by telephone when further information was needed. RESULTS: We
      identified 13 patients with significant gastric-wall hyperactivity, which was
      more intense on rest images. Our review of the clinical data shows that all these
      patients were suffering from dyspepsia and were taking gastric medication. These
      13 cases were assigned to 3 groups: gastroesophageal reflux, chronic functional
      dyspepsia and nonspecific gastritis. Significant gastric-wall hyperactivity is an
      infrequent observation on sestamibi cardiac SPECT. Our results indicate that the
      presence of significant gastric-wall hyperactivity is associated with dyspepsia.
      CONCLUSION: It is important to realize that this gastric-wall hyperactivity by
      its proximity to the inferior myocardial wall could in some circumstances lead to
      either false-negative or false-positive findings, representing a diagnostic
      problem. Although infrequent, this situation could be avoided by proper quality
      control, including a systematic review of the raw cine data before reading the
      images.

PMID- 15237781
TI  - Gender differences: from discrimination to acceptance.

PMID- 15237782
TI  - Finding help after homicide.

PMID- 15237783
TI  - Praise for "Relationships between incarcerated women".

PMID- 15237784
TI  - "Fallen apples" rings true for many.

PMID- 15237785
TI  - "Fallen apples" rings true for many.

PMID- 15237786
TI  - "Fallen apples" rings true for many.

PMID- 15237787
TI  - Telephone intervention works to stop intimate partner violence.

PMID- 15237788
TI  - The brain's rewarding system & addiction.

PMID- 15237789
TI  - Educating women about the hidden dangers of alcohol.
AB  - 1. There is mounting research evidence that alcohol use and abuse affects women
      much differently than men. 2. Research indicates that women absorb and metabolize
      alcohol differently than men, partly due to body composition differences and the
      production of less gastric alcohol dehydrogenase by women. 3. Women of child
      bearing age who engage in binge drinking are at increased risk of bearing
      children with fetal alcohol syndrome or alcohol-related neurological deficits. 4.
      Psychiatric nurses are often in the position to provide education and counseling
      to women regarding the hidden dangers of alcohol use and abuse.

PMID- 15237790
TI  - Understanding those who self-mutilate.
AB  - Self-mutilating behavior is a symptom seen in both men and women with various
      psychiatric disorders, but the majority of those who self-mutilate are women with
      borderline personality disorder. This complex, maladaptive behavior is used by
      clients as a means of self-preservation and emotion regulation, and is often
      associated with childhood trauma. Clients who self-mutilate perceive they receive
      poor care in hospital emergency departments and are retraumatized by these
      experiences. Clinicians who understand the complexity and purposes of self
      mutilating behavior are better able to provide clients with supportive,
      empathetic care.

PMID- 15237791
TI  - Using scrapbooks & portfolios in group work with women who are chemically
      dependent.
AB  - This article provides a rationale and strategies for using scrapbooks and
      portfolios within the context of group work with minority women recovering from
      chemical dependence. An expanded model of recovery-based group work places the
      use of scrapbooks and portfolios within the context of a practice model that
      seeks to increase general and social self-efficacy in these women. Memory
      scrapbooks, lifecourse scrapbooks, and recovery portfolios are defined; their
      differential use in group work is described; and ways group members can use the
      tools to strengthen their sources of self-efficacy are explored.

PMID- 15237792
TI  - Living with postpartum depression.

PMID- 15237806
TI  - Localization of marine mammals near Hawaii using an acoustic propagation model.
AB  - Humpback whale songs were recorded on six widely spaced receivers of the Pacific
      Missile Range Facility (PMRF) hydrophone network near Hawaii during March of
      2001. These recordings were used to test a new approach to localizing the whales
      that exploits the time-difference of arrival (time lag) of their calls as
      measured between receiver pairs in the PMRF network. The usual technique for
      estimating source position uses the intersection of hyperbolic curves of constant
      time lag, but a drawback of this approach is its assumption of a constant wave
      speed and straight-line propagation to associate acoustic travel time with range.
      In contrast to hyperbolic fixing, the algorithm described here uses an acoustic
      propagation model to account for waveguide and multipath effects when estimating
      travel time from hypothesized source positions. A comparison between predicted
      and measured time lags forms an ambiguity surface, or visual representation of
      the most probable whale position in a horizontal plane around the array. This is
      an important benefit because it allows for automated peak extraction to provide a
      location estimate. Examples of whale localizations using real and simulated data
      in algorithms of increasing complexity are provided.

PMID- 15237800
TI  - Quantifying elasticity and viscosity from measurement of shear wave speed
      dispersion.
AB  - The propagation speed of shear waves is related to frequency and the complex
      stiffness (shear elasticity and viscosity) of the medium. A method is presented
      to solve for shear elasticity and viscosity of a homogeneous medium by measuring
      shear wave speed dispersion. Harmonic radiation force, introduced by modulating
      the energy density of incident ultrasound, is used to generate cylindrical shear
      waves of various frequencies in a homogeneous medium. The speed of shear waves is
      measured from phase shift detected over the distance propagated. Measurements of
      shear wave speed at multiple frequencies are fit with the theoretical model to
      solve for the complex stiffness of the medium. Experiments in gelatin phantoms
      show promising results validated by an independent method. Practical
      considerations and challenges in possible medical applications are discussed.

PMID- 15237809
TI  - Temperature dependence of ultrasonic propagation speed and attenuation in excised
      canine liver tissue measured using transmitted and reflected pulses.
AB  - Previous reported data from our laboratory demonstrated the temperature
      dependence of propagation speed and attenuation of canine tissue in vitro at
      discrete temperatures ranging from 25 to 95 degrees C. However, concerns were
      raised regarding heating the same tissue specimen over the entire temperature
      range, a process that may introduce irreversible and, presumably, cumulative
      tissue degradation. In this paper propagation speed and attenuation vs
      temperature are measured using multiple groups of samples, each group heated to a
      different temperature. Sample thicknesses are measured directly using a technique
      that uses both transmitted and reflected ultrasound pulses. Results obtained
      using 3 and 5 MHz center frequencies demonstrate a propagation speed elevation of
      around 20 m/s in the 22-60 degrees C range, and a decrease of 15 m/s in the 60-90
      degrees C range, in agreement with previous results where the same specimens were
      subjected to the entire temperature range. However, sound speed results reported
      here are slightly higher than those reported previously, probably due to more
      accurate measurements of sample thickness in the present experiments. Results
      also demonstrate that while the propagation speed varies with temperature, it is
      not a function of tissue coagulation. In contrast, the attenuation coefficient
      depends on both tissue coagulation effects and temperature elevation.

PMID- 15237812
TI  - Transient temperature rise due to ultrasound absorption at a bone/soft-tissue
      interface.
AB  - Thermal effects due to high ultrasound absorption in bone pose an ongoing safety
      issue. Of considerable concern is the heating of the soft tissue adjacent to the
      bone surface. Mathematical models can be useful in predicting the transient
      temperature near the interface during insonation. This paper develops a model
      that provides the temperature field in terms of simple expressions that convey
      the functional dependence of the material properties, and are easily incorporated
      into standards and ultrasound machine software, yet are able to incorporate the
      material properties of both bone and soft tissue. The model contains an
      asymptotic theory based upon a "high-attenuation" assumption: the distance
      diffused by heat over the time of interest is large compared to the ultrasound
      attenuation length. Model predictions of temperature rise and location of maximum
      temperature were in close agreement with finite-element calculations, using
      parameters appropriate for radiation-force imaging and focused-ultrasound
      surgery.

PMID- 15237815
TI  - 1-3 piezoelectric composite transducers for swept-frequency calibration of
      hydrophones from 100 kHz to 2 MHz.
AB  - Rapid calibration of hydrophones used in biomedical ultrasound is possible with
      swept frequency techniques such as time delay spectrometry. However, calibrations
      below 2 MHz largely have been neglected because of insufficient transmitting
      transducer bandwidth, even though important medical applications operate in this
      range. To address this deficiency, several transmitting transducer designs were
      developed and tested, and two 1-3 piezoelectric composite designs were found to
      have the requisite bandwidth and uniformity of response. In one the element has a
      plane front face and spherically concave back face (plano-concave), and in the
      second both faces are concave, but with different radii of curvature (biconcave).
      The nonuniform thickness disperses the thickness resonance, and the composite
      structure suppresses radial-mode resonances. Also, the composite's lower acoustic
      impedance provides a more efficient match to water. The piezoelectric composite
      transducers were found to have transmitting pressure sensitivities superior to
      ceramic single-element and segmented designs having similar dimensions, and their
      responses were significantly more uniform (< 25 dB variation from 0.1-2 MHz, with
      < 1 dB fine structure variation), likely due to decreased contributions from
      radial modes.

PMID- 15237820
TI  - Active control of radiation from a piston set in a rigid sphere.
AB  - Active control of the sound radiated from a piston set in a rigid sphere with a
      set of control point sources around is considered in this paper, where the
      scattering sound field of the control sound from the rigid sphere has been taken
      into account to minimize the total radiated sound power. Analytic results of the
      sound power are obtained and numerical simulations show that it is possible to
      reduce the radiation from a small piston set in a rigid sphere similar to the
      size of a human head up to a certain frequency. It is found that the introduction
      of the scattering object makes significant differences from the active control
      without scattering objects. This being the case, the scattering object makes the
      active noise control easier. To increase the global reduction of sound-power
      output, the optimal number and locations of the control sources and the optimal
      number and locations of error sensors are discussed. Finally, experiments with
      one control source and one error sensor around a head simulator have been carried
      out to verify the simulation results.

PMID- 15237821
TI  - Children's perceptions of their acoustic environment at school and at home.
AB  - This paper describes the results of a large-scale questionnaire survey that
      ascertained children's perceptions of their noise environment and the
      relationships of the children's perceptions to objective measures of noise.
      Precision, specificity, and consistency of responding was established through the
      use of convergent measures. Two thousand and thirty-six children completed a
      questionnaire designed to tap (a) their ability to discriminate different
      classroom listening conditions; (b) the noise sources heard at home and at
      school; and (c) their annoyance by these noise sources. Teachers completed a
      questionnaire about the classroom noise sources. Children were able to
      discriminate between situations with varying amounts and types of noise. A
      hierarchy of annoying sound sources for the children was established. External
      L(Amax) levels were a significant factor in reported annoyance, whereas external
      L(A90) and L(A99) levels were a significant factor in determining whether or not
      children hear sound sources. Objective noise measures (L(A90) and L(A99))
      accounted for 45% of the variance in children's reporting of sounds in their
      school environment. The current study demonstrates that children can be sensitive
      judges of their noise environments and that the impact of different aspects of
      noise needs to be considered. Future work will need to specify the factors
      underlying the developmental changes and the physical and location dimensions
      that determine the school effects.

PMID- 15237822
TI  - Soft-computing base analyses of the relationship between annoyance and coping
      with noise and odor.
AB  - The majority of research on annoyance as an important impact of noise, odor, and
      other stressors on man, has regarded the person as a passive receptor. It was
      however recognized that this person is an active participant trying to alter a
      troubled person-environment relationship or to sustain a desirable one. Coping
      has to be incorporated. This is of particular importance in changing exposure
      situations. For large populations a lot of insight can be gained by looking at
      average effects only. To investigate changes in annoyance and effects of coping,
      the individual or small group has to be studied. Then it becomes imperative to
      recognize the inherent vagueness in perception and human behavior. Fortunately,
      tools have been developed over the past decades that allow doing this in a
      mathematically precise way. These tools are sometimes referred to by the common
      label: soft-computing, hence the title of this paper. This work revealed
      different styles of coping both by blind clustering and by (fuzzy) logical
      aggregation of different actions reported in a survey. The relationship between
      annoyance and the intensity of coping it generates was quantified after it was
      recognized that the possibility for coping is created by the presence of the
      stressor rather than the actual fact of coping. It was further proven that
      refinement of this relationship is possible if a person can be identified as a
      coper. This personal factor can be extracted from a known reaction to one
      stressor and be used for predicting coping intensity and style in another
      situation. The effect of coping on a perceived change in annoyance is quantified
      by a set of fuzzy linguistic rules. This closes the loop that is responsible for
      at least some of the dynamics of the response to a stressor. This work thus
      provides all essential building blocks for designing models for annoyance in
      changing environments.

PMID- 15237824
TI  - Estimation of ultrasound wave aberration with signals from random scatterers.
AB  - A method for estimating waveform aberration from random scatterers in medical
      ultrasound imaging has been derived and its properties investigated using two
      dimensional simulations. The method uses a weighted and modified cross-spectrum
      in order to estimate arrival time and amplitude fluctuations from received
      signals. The arrival time and amplitude fluctuations were used in a time delay,
      and a time delay and amplitude aberration correction filter, for evaluation of
      the retransmitted aberration corrected signal. Different types of aberration have
      been used in this study. First, aberration was concentrated on the plane of the
      transmitting/receiving array. Second, aberration was generated with a distributed
      aberrator. Both conditions emulated aberration from the human abdominal wall.
      Results show that for the concentrated aberrator, arrival time and amplitude
      fluctuations were estimated in close agreement with reference values. The
      reference values were obtained from simulations with a point source in the focal
      point of the array. Correction of the transmitted signal with a time delay, and a
      time delay and amplitude filter produced approximately equal correction as with
      point source estimates. For the distributed aberrator, the estimator performance
      degraded significantly. Arrival time and amplitude fluctuations deviated from
      reference values, leading to a limited correction of the retransmitted signal.

PMID- 15237827
TI  - An efficient robust sound classification algorithm for hearing aids.
AB  - An efficient robust sound classification algorithm based on hidden Markov models
      is presented. The system would enable a hearing aid to automatically change its
      behavior for differing listening environments according to the user's
      preferences. This work attempts to distinguish between three listening
      environment categories: speech in traffic noise, speech in babble, and clean
      speech, regardless of the signal-to-noise ratio. The classifier uses only the
      modulation characteristics of the signal. The classifier ignores the absolute
      sound pressure level and the absolute spectrum shape, resulting in an algorithm
      that is robust against irrelevant acoustic variations. The measured
      classification hit rate was 96.7%-99.5% when the classifier was tested with
      sounds representing one of the three environment categories included in the
      classifier. False-alarm rates were 0.2%-1.7% in these tests. The algorithm is
      robust and efficient and consumes a small amount of instructions and memory. It
      is fully possible to implement the classifier in a DSP-based hearing instrument.

PMID- 15237831
TI  - Eigenfunction analysis of stochastic backscatter for characterization of acoustic
      aberration in medical ultrasound imaging.
AB  - Presented here is a characterization of aberration in medical ultrasound imaging.
      The characterization is optimal in the sense of maximizing the expected energy in
      a modified beamformer output of the received acoustic backscatter. Aberration
      correction based on this characterization takes the form of an aberration
      correction filter. The situation considered is frequently found in applications
      when imaging organs through a body wall: aberration is introduced in a layer
      close to the transducer, and acoustic backscatter from a scattering region behind
      the body wall is measured at the transducer surface. The scattering region
      consists of scatterers randomly distributed with very short correlation length
      compared to the acoustic wavelength of the transmit pulse. The scatterer
      distribution is therefore assumed to be delta correlated. This paper shows how
      maximizing the expected energy in a modified beamformer output signal naturally
      leads to eigenfunctions of a Fredholm integral operator, where the associated
      kernel function is a spatial correlation function of the received stochastic
      signal. Aberration characterization and aberration correction are presented for
      simulated data constructed to mimic aberration introduced by the abdominal wall.
      The results compare well with what is obtainable using data from a simulated
      point source.

PMID- 15237832
TI  - Siamang gibbons exceed the saccular threshold: intensity of the song of Hylobates
      syndactylus.
AB  - Measurements are reported of the intensity of the siamang gibbon loud call
      obtained from the vocal bouts of three family groups at Twycross Zoo, UK. Across
      25 samples the maximum intensity ranged from 95 to 113 dB SPL (linear frequency
      weighting and fast time-weighting) and exhibited three frequency modes of 250-315
      Hz, 630-800 Hz and 1.2-1.6 kHz. The lowest frequency mode, which may correspond
      to the "boom" sound produced by resonance of the siamang inflated vocal sac, had
      a mean maximum intensity of 99 dB SPL. These values, which are in excess of the
      saccular acoustic threshold of about 90 dB at 300 Hz for air conducted sound,
      suggest that primate loud calls recruit a primitive mode of acoustic sensitivity
      furnished by the sacculus. Thus reproductive vocal behavior of primates may be
      influenced by a primitive acoustical reward pathway inherited from a common
      ancestor with anamniotes. In humans such a pathway could explain the compulsion
      for exposure to loud music.

PMID- 15237833
TI  - Similarity in loudness and distortion product otoacoustic emission input/output
      functions: implications for an objective hearing aid adjustment.
AB  - The aim of the present study was to compare distortion product otoacoustic
      emissions (DPOAEs) to loudness with regard to the potentiality of DPOAEs to
      determine characteristic quantities of the cochlear-impaired ear and to derive
      objective hearing aid parameters. Recently, Neely et al. [J. Acoust. Soc. Am.
      114, 1499-1507 (2003)] compared DPOAE input/output functions to the Fletcher and
      Munson [J. Acoust. Soc. Am. 5, 82-108 (1933)] loudness function finding a close
      resemblance in the slope characteristics of both measures. The present study
      extended their work by performing both loudness and DPOAE measurements in the
      same subject sample, and by developing a method for the estimation of gain needed
      to compensate for loss of cochlear sensitivity and compression. DPOAEs and
      loudness exhibited similar behavior when plotted on a logarithmic scale and slope
      increased with increasing hearing loss, confirming the findings of Neely et al.
      To compensate for undesired nonpathological impacts on the magnitude of DPOAE
      level, normalization of DPOAE data was implemented. A close resemblance between
      gain functions based on loudness and normalized DPOAE data was achieved. These
      findings suggest that DPOAEs are able to quantify the loss of cochlear
      sensitivity and compression and thus might provide parameters for a
      noncooperative hearing aid adjustment.

PMID- 15237834
TI  - Development of auditory sensitivity in budgerigars (Melopsittacus undulatus).
AB  - Auditory feedback influences the development of vocalizations in songbirds and
      parrots; however, little is known about the development of hearing in these
      birds. The auditory brainstem response was used to track the development of
      auditory sensitivity in budgerigars from hatch to 6 weeks of age. Responses were
      first obtained from 1-week-old at high stimulation levels at frequencies at or
      below 2 kHz, showing that budgerigars do not hear well at hatch. Over the next
      week, thresholds improved markedly, and responses were obtained for almost all
      test frequencies throughout the range of hearing by 14 days. By 3 weeks
      posthatch, birds' best sensitivity shifted from 2 to 2.86 kHz, and the shape of
      the auditory brainstem response (ABR) audiogram became similar to that of adult
      budgerigars. About a week before leaving the nest, ABR audiograms of young
      budgerigars are very similar to those of adult birds. These data complement what
      is known about vocal development in budgerigars and show that hearing is fully
      developed by the time that vocal learning begins.

PMID- 15237835
TI  - Testing the concept of softness imperception: loudness near threshold for hearing
      impaired ears.
AB  - Buus and Florentine [J. Assoc. Res. Otolaryngol. 3, 120-139 (2002)] have proposed
      that loudness recruitment in cases of cochlear hearing loss is caused partly by
      an abnormally large loudness at absolute threshold. This has been called
      "softness imperception." To evaluate this idea, loudness-matching functions were
      obtained using tones at very low sensation levels. For subjects with asymmetrical
      hearing loss, matches were obtained for a single frequency across ears. For
      subjects with sloping hearing loss, matches were obtained between tones at two
      frequencies, one where the absolute threshold was nearly normal and one where
      there was a moderate hearing loss. Loudness matching was possible for sensation
      levels (SLs) as low as 2 dB. When the fixed tone was presented at a very low SL
      in an ear (or at a frequency) where there was hearing impairment, it was matched
      by a tone with approximately the same SL in an ear (or at a frequency) where
      hearing was normal (e.g., 2 dB SL matched 2 dB SL). This relationship held for
      SLs up to 4-10 dB, depending on the subject. These results are not consistent
      with the concept of softness imperception.

PMID- 15237836
TI  - The temporal growth and decay of the auditory motion aftereffect.
AB  - The present work investigated the temporal tuning of the auditory motion
      aftereffect (aMAE) by measuring the time course of adaptation and recovery to
      auditory motion exposure. On every trial, listeners were first exposed to a
      broadband, horizontally moving sound source for either 1 or 5 seconds, then
      presented moving test stimuli after delays of 0, 2/3, or 1 2/3 seconds. All
      stimuli were synthesized from head related transfer functions recorded for each
      participant. One second of motion exposure (i.e., a single pass of the moving
      source) produced clearly measurable aMAEs which generally decayed monotonically
      after adaptation ended, while five seconds exposure produced stronger
      aftereffects that remained largely unattenuated across test delays. These
      differences may imply two components to the aMAE: a short time-constant motion
      illusion and a longer time-constant response bias. Finally, aftereffects were
      produced only by adaptor movement toward but not away from listener midline. This
      aftereffect asymmetry may also be a consequence of brief adaptation times and
      reflect initial neural response to auditory motion in primate auditory cortex.

PMID- 15237837
TI  - Contrasting monaural and interaural spectral cues for human sound localization.
AB  - A human psychoacoustical experiment is described that investigates the role of
      the monaural and interaural spectral cues in human sound localization. In
      particular, it focuses on the relative contribution of the monaural versus the
      interaural spectral cues towards resolving directions within a cone of confusion
      (i.e., directions with similar interaural time and level difference cues) in the
      auditory localization process. Broadband stimuli were presented in virtual space
      from 76 roughly equidistant locations around the listener. In the experimental
      conditions, a "false" flat spectrum was presented at the left eardrum. The sound
      spectrum at the right eardrum was then adjusted so that either the true right
      monaural spectrum or the true interaural spectrum was preserved. In both cases,
      the overall interaural time difference and overall interaural level difference
      were maintained at their natural values. With these virtual sound stimuli, the
      sound localization performance of four human subjects was examined. The
      localization performance results indicate that neither the preserved interaural
      spectral difference cue nor the preserved right monaural spectral cue was
      sufficient to maintain accurate elevation judgments in the presence of a flat
      monaural spectrum at the left eardrum. An explanation for the localization
      results is given in terms of the relative spectral information available for
      resolving directions within a cone of confusion.

PMID- 15237838
TI  - Localization dominance in the median-sagittal plane: effect of stimulus duration.
AB  - Localization dominance is an aspect of the precedence effect (PE) in which the
      leading source dominates the perceived location of a simulated echo (lagging
      source). It is known to be robust in the horizontal/azimuthal dimension, where
      binaural cues dominate localization. However, little is known about localization
      dominance in conditions that minimize binaural cues, and most models of
      precedence treat the phenomena as "belonging" to the binaural system. Here,
      localization dominance in the median-sagittal plane was studied where binaural
      cues are greatly reduced, and monaural spectral/level cues are thought to be the
      primary cues used for localization. Lead-lag pairs of noise bursts were presented
      from locations spaced in 15 degrees increments in the frontal, median-sagittal
      plane, with a 2-ms delay in their onsets, for source durations of 1, 10, 25, and
      50-ms. Intermixed with these trials were single-speaker trials, in which lead and
      lag were summed and presented from one speaker. Listeners identified the speaker
      that was nearest to the perceived source location. With single-speaker stimuli,
      localization improves as signal duration is increased. Furthermore, evidence of
      elevation compression was found with a dependence on duration. With lead-lag
      pairs, localization dominance occurs in the median plane, and becomes more robust
      with increased signal duration. These results suggest that accurate localization
      of a co-located lead-lag pair is necessary for localization dominance to occur
      when the lag is spatially separated from the lead.

PMID- 15237839
TI  - Sensitivity to interaural intensitive disparities: listeners' use of potential
      cues.
AB  - Thresholds for interaural intensitive disparities (IIDs) for a 500-Hz tone were
      measured in several stimulus conditions including those in which the use of
      intracranial position as a cue was effectively eliminated by roving the
      interaural temporal disparity of the stimuli. Removing position as a cue resulted
      in substantial degradation of sensitivity to IID. The overall patterning of the
      data suggests that threshold-IIDs measured in standard binaural paradigms that
      yield fused intracranial images reflect the use of changes in intracranial
      position. That is, comparisons among the data suggest that listeners' judgments
      depend upon binaural spatial cues and not on comparisons of the concomitant
      monaural increments and decrements in level, per se, that inevitably result from
      the imposition of IIDs.

PMID- 15237840
TI  - Measurements of vocal fold tissue viscoelasticity: approaching the male phonatory
      frequency range.
AB  - Viscoelastic shear properties of human vocal fold tissues have been reported
      previously. However, data have only been obtained at very low frequencies (< or =
      15 Hz). This necessitates data extrapolation to the frequency range of phonation
      based on constitutive modeling and time-temperature superposition. This study
      attempted to obtain empirical measurements at higher frequencies with the use of
      a controlled strain torsional rheometer, with a design of directly controlling
      input strain that introduced significantly smaller system inertial errors
      compared to controlled stress rheometry. Linear viscoelastic shear properties of
      the vocal fold mucosa (cover) from 17 canine larynges were quantified at
      frequencies of up to 50 Hz. Consistent with previous data, results showed that
      the elastic shear modulus (G'), viscous shear modulus (G"), and damping ratio
      (zeta) of the vocal fold mucosa were relatively constant across 0.016-50 Hz,
      whereas the dynamic viscosity (eta') decreased monotonically with frequency.
      Constitutive characterization of the empirical data by a quasilinear viscoelastic
      model and a statistical network model demonstrated trends of viscoelastic
      behavior at higher frequencies generally following those observed at lower
      frequencies. These findings supported the use of controlled strain rheometry for
      future investigations of the viscoelasticity of vocal fold tissues and
      phonosurgical biomaterials at phonatory frequencies.

PMID- 15237841
TI  - Listener sensitivity to individual talker differences in voice-onset-time.
AB  - Recent findings in the domains of word and talker recognition reveal that
      listeners use previous experience with an individual talker's voice to facilitate
      subsequent perceptual processing of that talker's speech. These findings raise
      the possibility that listeners are sensitive to talker-specific acoustic-phonetic
      properties. The present study tested this possibility directly by examining
      listeners' sensitivity to talker differences in the voice-onset-time (VOT)
      associated with a word-initial voiceless stop consonant. Listeners were trained
      on the speech of two talkers. Speech synthesis was used to manipulate the VOTs of
      these talkers so that one had short VOTs and the other had long VOTs
      (counterbalanced across listeners). The results of two experiments using a paired
      comparison task revealed that, when presented with a short- versus long-VOT
      variant of a given talker's speech, listeners could select the variant consistent
      with their experience of that talker's speech during training. This was true when
      listeners were tested on the same word heard during training and when they were
      tested on a different word spoken by the same talker, indicating that listeners
      generalized talker-specific VOT information to a novel word. Such sensitivity to
      talker-specific acoustic-phonetic properties may subserve at least in part
      listeners' capacity to benefit from talker-specific experience.

PMID- 15237842
TI  - Adult-child differences in acoustic cue weighting are influenced by segmental
      context: children are not always perceptually biased toward transitions.
AB  - It has been proposed that young children may have a perceptual preference for
      transitional cues [Nittrouer, S. (2002). J. Acoust. Soc. Am. 112, 711-719].
      According to this proposal, this preference can manifest itself either as heavier
      weighting of transitional cues by children than by adults, or as heavier
      weighting of transitional cues than of other, more static, cues by children. This
      study tested this hypothesis by examining adults' and children's cue weighting
      for the contrasts /saI/-/integral of aI/, /de/-/be/, /ta/-/da/, and /ti/-/di/.
      Children were found to weight transitions more heavily than did adults for the
      fricative contrast /saI/-/integral aI/, and were found to weight transitional
      cues more heavily than nontransitional cues for the voice-onset-time contrast
      /ta/-/da/. However, these two patterns of cue weighting were not found to hold
      for the contrasts /de/-/be/ and /ti/-/di/. Consistent with several studies in the
      literature, results suggest that children do not always show a bias towards vowel
      formant transitions, but that cue weighting can differ according to segmental
      context, and possibly the physical distinctiveness of available acoustic cues.

PMID- 15237843
TI  - Rational approximations of viscous losses in vocal tract acoustic modeling.
AB  - The modeling of viscous losses in acoustic wave transmission through tubes by a
      boundary layer approximation is valid if the thickness of the boundary layer is
      small compared to the hydraulic radius. A method was found to describe the
      viscous losses that extends the frequency range of the model to very low
      frequencies and very thin tubes. For higher frequencies, this method includes
      asymptotically the spectral effects of the boundary layer approximation. The
      method provides a simplification for the rational approximation of the spectral
      effects of viscous losses.

PMID- 15237844
TI  - A continuous-wave ultrasound system for displacement amplitude and phase
      measurement.
AB  - A noninvasive, continuous-wave ultrasonic technique was developed to measure the
      displacement amplitude and phase of mechanical structures. The measurement system
      was based on a method developed by Rogers and Hastings ["Noninvasive vibration
      measurement system and method for measuring amplitude of vibration of tissue in
      an object being investigated," U.S. Patent No. 4,819,643 (1989)] and expanded to
      include phase measurement. A low-frequency sound source was used to generate
      harmonic vibrations in a target of interest. The target was simultaneously
      insonified by a low-power, continuous-wave ultrasonic source. Reflected
      ultrasound was phase modulated by the target motion and detected with a separate
      ultrasonic transducer. The target displacement amplitude was obtained directly
      from the received ultrasound frequency spectrum by comparing the carrier and
      sideband amplitudes. Phase information was obtained by demodulating the received
      signal using a double-balanced mixer and low-pass filter. A theoretical model for
      the ultrasonic receiver field is also presented. This model coupled existing
      models for focused piston radiators and for pulse-echo ultrasonic fields.
      Experimental measurements of the resulting receiver fields compared favorably
      with theoretical predictions.

PMID- 15237845
TI  - Feasibility of bone assessment with leaky Lamb waves in bone phantoms and a
      bovine tibia.
AB  - In this study, the effect of cortical thickness variation on the propagation of
      leaky Lamb waves is investigated by using an axial transmission technique
      commonly used to characterize long bones. Three Lucite plates with thicknesses of
      1, 3, and 5 mm as bone phantoms and one bovine tibia with a cortical thickness of
      2 mm were used at various low frequencies. Experimental measurements in bone
      phantoms show that the peak frequency and amplitude of excited Lamb modes
      strongly depend on the thickness of the Lucite plate. In the bovine tibia, the S0
      and A0 Lamb modes are consistently observed in the frequency-thickness region
      from 0.2 to 1.0 MHz mm, and can be effectively launched at a frequency of 200
      kHz, suggesting 200 kHz to be the optimal signal frequency for in vivo clinical
      applications. It can be also seen that both modes are affected by the frequency
      thickness product, but the effect is greater for the A0 mode. Hence, the A0 Lamb
      mode seems more sensitive to cortical thickness change due to aging and
      osteoporosis. This study suggests that the use of leaky Lamb waves is feasible
      for ultrasonic bone assessment.

PMID- 15237846
TI  - The interaction of outgoing echolocation pulses and echoes in the false killer
      whale's auditory system: evoked-potential study.
AB  - Brain auditory evoked potentials (AEP) associated with echolocation were recorded
      in a false killer whale Pseudorca crassidens trained to accept suction-cup EEG
      electrodes and to detect targets by echolocation. AEP collection was triggered by
      echolocation pulses transmitted by the animal. The target was a hollow aluminum
      cylinder of strength of -22 dB at a distance from 1 to 8 m. Each AEP record was
      obtained by averaging more than 1000 individual records. All the records
      contained two AEP sets: the first one of a constant latency and a second one with
      a delay proportional to the distance. The timing of these two AEP sets was
      interpreted as responses to the transmitted echolocation pulse and echo,
      respectively. The echo-related AEP, although slightly smaller, was comparable to
      the outgoing click-related AEP in amplitude, even though at a target distance as
      far as 8 m the echo intensity was as low as -64 dB relative to the transmitted
      pulse in front of the head. The amplitude of the echo-related AEP was almost
      independent of distance, even though variation of target distance from 1 to 8 m
      influenced the echo intensity by as much as 36 dB.

PMID- 15237847
TI  - Defining optimal axial and lateral resolution for estimating scatterer properties
      from volumes using ultrasound backscatter.
AB  - The rf signals used to construct conventional ultrasound B-mode images contain
      frequency-dependent information that can be examined through the backscattered
      power spectrum. Typically, the backscattered power spectrum is calculated from a
      region of interest (ROI) within some larger volume. The dimensions of the ROI are
      defined axially by the spatial length corresponding to the time gate and
      laterally by the number of scan lines included in the ROI. Averaging the
      backscattered power spectra from several independent scan lines can reduce the
      presence of noise caused by electronics and by the random scatterer spacings, but
      also decreases the lateral resolution of the interrogation region. Furthermore,
      larger axial gate lengths can be used to reduce the effects of noise and improve
      the precision and accuracy of scatterer property estimates but also decreases the
      axial resolution. A trade-off exists between the size of the ROI (the number of
      scan lines used, the separation distance between each scan line, the axial gate
      length) and the accuracy and precision of scatterer property estimates. A series
      of simulations and measurements from physical phantoms were employed to examine
      these trade-offs. The simulations and phantom measurements indicated the optimal
      lateral and axial sizes of the ROI, where estimate accuracy and precision were
      better than 10% and 5%, respectively, occurred at 4 to 5 beamwidths laterally and
      15 to 20 spatial pulse lengths axially.

PMID- 15237848
TI  - Forced linear oscillations of microbubbles in blood capillaries.
AB  - A theoretical investigation of the forced linear oscillations of a gas
      microbubble in a blood capillary, whose radius is comparable in size to the
      bubble radius is presented. The natural frequency of oscillation, the thermal and
      viscous damping coefficients, the amplitude resonance, the energy resonance, as
      well as the average energy absorbed by the system, bubble plus vessel, have been
      computed for different kinds of gas microbubbles, containing air,
      octafluropropane, and perflurobutane as a function of the bubble radius and
      applied frequency. It has been found that the bubble behavior is isothermal at
      low frequencies and for small bubbles and between isothermal and adiabatic for
      larger bubbles and higher frequencies, with the viscous damping dominating over
      the thermal damping. Furthermore, the width of the energy resonance is strongly
      dependent on the bubble size and the natural frequency of oscillation is affected
      by the presence of the vessel wall and position of the bubble in the vessel.
      Therefore, the presence of the blood vessel affects the way in which the bubble
      absorbs energy from the ultrasonic field. The motivation of this study lies in
      the possibility of using gas microbubbles as an aid to therapeutic focused
      ultrasound treatments.

PMID- 15237849
TI  - Errors in ultrasonic scatterer size estimates due to phase and amplitude
      aberration.
AB  - Current ultrasonic scatterer size estimation methods assume that acoustic
      propagation is free of distortion due to large-scale variations in medium
      attenuation and sound speed. However, it has been demonstrated that under certain
      conditions in medical applications, medium inhomogeneities can cause significant
      field aberrations that lead to B-mode image artifacts. These same aberrations may
      be responsible for errors in size estimates and parametric images of scatterer
      size. This work derives theoretical expressions for the error in backscatter
      coefficient and size estimates as a function of statistical parameters that
      quantify phase and amplitude aberration, assuming a Gaussian spatial
      autocorrelation function. Results exhibit agreement with simulations for the
      limited region of parameter space considered. For large values of aberration
      decorrelation lengths relative to aberration standard deviations, phase
      aberration errors appear to be minimal, while amplitude aberration errors remain
      significant. Implications of the results for accurate backscatter and size
      estimation are discussed. In particular, backscatter filters are suggested as a
      method for error correction. Limitations of the theory are also addressed. The
      approach, approximations, and assumptions used in the derivation are most
      appropriate when the aberrating structures are relatively large, and the region
      containing the inhomogeneities is offset from the insonifying transducer.

PMID- 15237850
TI  - Cytochrome P450: what have we learned and what are the future issues?
AB  - The cytochrome P450 (P450) field came out of interest in the metabolism of drugs,
      carcinogens, and steroids, which remain major focal points. Over the years we
      have come to understand the P450 system components, the multiplicity of P450s,
      and many aspects of the regulation of the genes and also the catalytic mechanism.
      Many crystal structures are now becoming available. The significance of P450 in
      in vivo metabolism is appreciated, particularly in the context of
      pharmacogenetics. Current scientific issues involve posttranslational
      modification, gene regulation, component interactions, structures of P450
      complexed with ligands, details of high-valent oxygen chemistry, the nature and
      influence of rate-limiting steps, greater details about some reaction steps,
      cooperativity, and the relevance of P450 variations to cancer risk. Some emerging
      research areas involve new methods of analysis of ligand interactions, roles of
      conformational changes linked to individual reaction steps, functions of orphan
      P450s, "molecular breeding" of new P450 functions and enhanced activity, and the
      utilization of P450s in chemical synthesis.

PMID- 15237852
TI  - "Allosterism" in the elementary steps of the cytochrome P450 reaction cycle.
AB  - Cytochrome P450-dependent drug metabolism in vitro frequently deviates from
      simple Michaelis-Menten kinetic models, and demonstrates both positive and
      negative homotropic and heterotropic effects. These complex "allsoteric" kinetics
      confound our ability to predict drug clearance, and they may provide a basis for
      drug-drug interactions. Although allosteric effects require that multiple
      substrates, or substrate and effector, are simultaneously bound to a cytochrome
      P450 (CYP), the mechanisms by which multiple ligand binding alters rates of
      individual steps in the CYP reaction cycle are incompletely characterized. In
      addition, it is unknown whether multiple ligands bind in discrete subsites within
      the large active site or whether they share a fluid dynamic site. These
      mechanistic aspects of multiple drug binding are addressed here via several
      spectroscopic probes including ultraviolet-vis difference spectroscopy, protein
      and ligand fluorescence, and 15N-edited HSQC nuclear magnetic resonance (NMR)
      with 15N-Phe-labeled CYPs. The results indicate a lack of correspondence between
      ligand binding per se and the ligand-dependent home spin state change when
      multiple ligands bind. Furthermore, the results provide proof of principle for
      NMR as a method for studying CYP allosterism, and demonstrate that the model
      ligand 9-aminophenanthrene binds in two discrete events to individual subsites
      within the active site of CYP(eryF).

PMID- 15237851
TI  - Genotoxic mechanism of tamoxifen in developing endometrial cancer.
AB  - Increased risk of developing endometrial cancers has been observed in women
      treated with tamoxifen (TAM), a widely used drug for breast cancer therapy and
      chemoprevention. The carcinogenic effect may be due to genotoxic DNA damage
      induced by TAM. In fact, TAM-DNA adducts were detected in the endometrium of
      women treated with this drug. TAM is alpha-hydroxylated by cytochrome P450 3A4
      followed by O-sulfonation by hydroxysteroid sulfotransferase, and reacts with
      guanine residues in DNA, resulting in the formation of alpha-(N2
      deoxyguanosinyl)tamoxifen adducts. During this metabolic process, short-lived
      carbocations are produced at the ethyl moiety of TAM as reactive intermediates.
      TAM-DNA adducts promote primarily G -->T transversions in mammalian cells. The
      same mutations have been frequently detected at codon 12 of the K-ras gene in the
      endometrial tissue of women treated with this drug. TAM-DNA adducts, if not
      readily repaired, may act as initiators, leading to development of endometrial
      cancers. The reactivity of TAM metabolites with DNA is inhibited in toremifene,
      where the hydrogen atom has been replaced by a chlorine atom at the ethyl moiety.
      Therefore, toremifene may be a safer alternative to TAM. This article describes
      an overview of the mechanism of TAM-DNA adduct formation, mutagenic events of
      this adduct, and detection of TAM-DNA adducts in the endometrium of women treated
      with TAM.

PMID- 15237853
TI  - Modeling kinetic data from in vitro drug metabolism enzyme experiments.
AB  - Modeling of in vitro enzyme kinetic data derived from drug metabolism experiments
      can greatly facilitate the drug development process because estimation of kinetic
      parameters can facilitate decision making regarding whether to continue
      development of a compound. From this information, predictions can be made
      regarding the "metabolic stability" of a compound and even the in vivo intrinsic
      clearance of the drug. Many drugs exhibit typical Michaelis-Menten-type kinetics
      in vitro that result in a hyperbolic kinetic profile from which Km and Vm can be
      readily estimated. However, it is increasingly being recognized that many drug
      compounds exhibit "atypical" enzyme kinetics in vitro, requiring use of more
      complex kinetic models for data fitting and parameter estimation. These atypical
      kinetic profiles may include sigmoidal kinetics (autoactivation), biphasic
      kinetics, substrate inhibition kinetics, and heterotropic cooperativity
      (activation). This article briefly summarizes the types of equations necessary to
      adequately model both typical and atypical kinetic profiles in order to
      facilitate correct estimation of the relevant kinetic parameters.

PMID- 15237854
TI  - Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates.
AB  - Cytochrome P450 2D6 (CYP2D6) is the first well-characterized polymorphic phase I
      drug-metabolizing enzyme, and more than 80 allelic variants have been identified
      for the CYP2D6 gene, located on human chromosome 22q13.1. Human debrisoquine and
      sparteine metabolism is subdivided into two principal phenotypes--extensive
      metabolizer and poor metabolizer--that arise from variant CYP2D6 genotypes. It
      has been estimated that CYP2D6 is involved in the metabolism and disposition of
      more than 20% of prescribed drugs, and most of them act in the central nervous
      system or on the heart. These drug substrates are characterized as organic bases
      containing one nitrogen atom with a distance about 5, 7, or 10 A from the
      oxidation site. Aspartic acid 301 and glutamic acid 216 were determined as the
      key acidic residues for substrate-enzyme binding through electrostatic
      interactions. CYP2D6 transgenic mice, generated using a lambda phage clone
      containing the complete wild-type CYP2D6 gene, exhibits enhanced metabolism and
      disposition of debrisoquine. This transgenic mouse line and its wild-type control
      are models for human extensive metabolizers and poor metabolizers, respectively,
      and would have broad application in the study of CYP2D6 polymorphism in drug
      discovery and development, and in clinical practice toward individualized drug
      therapy. Endogenous 5-methoxyindole- thylamines derived from 5-hydroxytryptamine
      were identified as high-affinity substrates of CYP2D6 that catalyzes their O
      demethylations with high enzymatic capacity and specificity. Thus, polymorphic
      CYP2D6 may play an important role in the interconversions of these psychoactive
      tryptamines, including a crucial step in a serotonin-melatonin cycle.

PMID- 15237855
TI  - Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism.
AB  - The human genome contains at least 17 genes that are members of the aldehyde
      dehydrogenase (ALDH) superfamily. These genes encode NAD(P)(+)-dependent enzymes
      that oxidize a wide range of aldehydes to their corresponding carboxylic acids.
      Aldehydes are highly reactive molecules that are intermediates or products
      involved in a broad spectrum of physiologic, biologic, and pharmacologic
      processes. Aldehydes are generated during retinoic acid biosynthesis and the
      metabolism of amino acids, lipids, carbohydrates, and drugs. Mutations in several
      ALDH genes are the molecular basis of inborn errors of metabolism and contribute
      to environmentally induced diseases.

PMID- 15237856
TI  - Clinical perspectives on xenobiotic-induced hepatotoxicity.
AB  - Drug-induced hepatotoxicity is an important cause of liver disease with
      significant medical, economic, legal, and regulatory implications. Clinically, it
      presents a diagnostic challenge to health care professionals since drug-induced
      liver disease can mimic the clinicopathologic features of all other acute and
      chronic liver diseases. However, individual drugs tend to have a characteristic
      clinical signature. Early identification of hepatotoxicity by either laboratory
      monitoring or patients' awareness as a result of education may avert serious
      liver injury in delayed idiosyncratic toxicity. Most adverse hepatic reactions
      require metabolism of the drug to reactive metabolites and free radicals, which
      then either lead to direct overwhelming lethal insult, nonlethal sensitization to
      the lethal effects of the innate immune system, or haptenization eliciting an
      immunoallergic response of the adaptive immune system. Besides licensed drugs,
      herbal and natural supplements are recognized as causing hepatotoxicity with
      increasing frequency as patients turn more and more to alternative medicine.

PMID- 15237857
TI  - The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs
      and genetics.
AB  - Cytochrome P450 (CYP) enzymes in the brain may have a role in the activation or
      inactivation of centrally acting drugs, in the metabolism of endogenous
      compounds, and in the generation of damaging toxic metabolites and/or oxygen
      stress. CYPs are distributed unevenly among brain regions, and are found in
      neurons, glial cells and at the blood-brain interface. They have been observed in
      mitochondrial membranes, in neuronal processes and in the plasma membrane, as
      well as in endoplastic reticulum. Brain CYPs are inducible by many common hepatic
      inducers, however many compounds affect liver and brain CYP expression
      differently, and some CYPs which are constitutively expressed in liver are
      inducible in brain. CYP induction is isozyme-, brain region-, cell type- and
      inducer-specific. While it is unlikely that brain CYPs contribute to overall
      clearance of xenobiotics, their punctate, region- and cell-specific expression
      suggests that CNS CYPs may create micro-environments in the brain with differing
      drug and metabolite levels (not detected or predicted by plasma drug monitoring).
      Coupled with the sensitivity of CNS CYPs to induction, this may in part account
      for inter-individual variation in response to centrally acting drugs and
      neurotoxins, and may have implications for individual variation in receptor
      adaptation and cross-tolerance to different drugs. In addition, genetic variation
      in brain CYPs, depending on the type of polymorphism (structural versus
      regulatory), will alter enzyme activity. These aspects of brain CYP expression
      regulation and genetic influences are illustrated in this review using mRNA,
      protein, and enzyme activity data for CYP2D1/6, CYP2E1 and CYP2B1/6 in rat and
      human brain. The role of CYP-mediated metabolism in the brain, a highly
      heterogeneous and complex organ, is a new and relatively unexplored field of
      scientific enquiry. It holds promise for furthering our undestanding of inter
      individual variability in response to centrally acting drugs as well as risk for
      neurological diseases and pathogies.

PMID- 15237858
TI  - Human carbonyl reduction pathways and a strategy for their study in vitro.
AB  - Carbonyl reduction plays a significant role in physiological processes throughout
      the body. Although much is known about endogenous carbonyl metabolism, much less
      is known about the roles of carbonyl-reducing enzymes in xenobiotic metabolism.
      Multiple pathways exist in humans for metabolizing carbonyl moieties of
      xenobiotics to their corresponding alcohols, readying these molecules for
      subsequent conjugation and/or excretion. When exploring carbonyl reduction
      clearance pathways for a drug development candidate, it is possible to assess the
      relative contributions of these enzymes due to their differences in subcellular
      locations, cofactor dependence, and inhibitor profiles. In addition, the
      contributions of these enzymes may be explored by varying incubation conditions,
      such as pH. Presently, individual isoforms of carbonyl-reducing enzymes are not
      widely available, either in recombinant or purified form. However, it is possible
      to study carbonyl reduction clearance pathways from simple experiments with
      commercially available reagents. This article provides an overview of carbonyl
      reducing enzymes, including some kinetic data for substrates and inhibitors. In
      addition, an experimental strategy for the study of these enzymes in vitro is
      presented.

PMID- 15237859
TI  - Physiological roles of xanthine oxidoreductase.
AB  - Xanthine oxidoreductase (XOR) is a major protein component of the milk fat
      globule membrane (MFGM) surrounding fat droplets in milk and its enzymology is
      well characterised. The enzyme is widely distributed in mammalian tissues and is
      generally accepted to be a key enzyme of purine catabolism. It catalyses the
      oxidation of a wide range of substrates and can pass electrons to molecular
      oxygen, generating reactive oxygen species (ROS); similar reduction of nitrite
      yields reactive nitrogen species (RNS). While XOR has been implicated in ischemia
      reperfusion injury, its involvement in normal physiological processes has been
      less studied. It is argued here that XOR-derived ROS and RNS play a role in
      innate immunity, specifically in the inflammatory response and in anti-microbial
      defense of the gastrointestinal tract. XOR-derived species could also be involved
      in signalling. Additionally, XOR is likely to play a part in metabolism of
      xenobiotics and has recently been shown to mediate the secretion of milk fat
      globules. The human enzyme has only relatively recently been characterized. The
      enzyme purified from breast milk shows very low enzymatic activity, and it is
      suggested that human XOR has evolved so as to be regulated by an exceptional
      range of pre- and posttranslational mechanisms.

PMID- 15237860
TI  - Practical aspects of transporter model systems: a case study involving SQV.
AB  - In this case study, in vitro and in vivo data were provided for saquinavir (SQV)
      showing that drug transporters play a significant role in the absorption and
      disposition of drugs. This article is focused on the more practical points with a
      technical emphasis. Currently many in vitro and in vivo experimental models have
      been developed to investigate drug transporter interactions for the prediction of
      how transporters may influence the pharmacokinetic behavior of drugs. In this
      review, the successful application, limitations and challenges of these models
      are emphasized.

PMID- 15237861
TI  - Stress- (and diet-) related regulation of hepatic nuclear receptors and its
      relevance for ABC-transporter functions.
AB  - Nuclear receptors (NRs) play an important role in maintaining cellular
      homeostasis. With clearly established roles in fatty acid metabolism and
      inflammation, peroxisome proliferator activated receptors (PPARs) and other
      nuclear receptors are essential in liver functioning. However, much less is known
      about the regulation of NRs themselves during inflammatory processes in the
      liver. Interestingly PPARs and other NRs are negative acute phase proteins
      because they become rapidly downregulated during the acute phase response.
      However, PPARs have important roles in modulating inflammatory responses. One of
      the mechanisms by which dietary or inflammatory stress is relieved involves the
      hepatic adenosine triphosphate-binding cassette (ABC) transporter proteins, which
      import and export a wide variety of substrates. These ABC transporters are under
      close control of several NRs. Because NRs play important roles in fatty acid
      metabolism and inflammation as well as in the regulation of bile production, they
      are reviewed here with respect to their role in dietary and stress-related
      responses of the liver and their impact on the regulation and function of hepatic
      ABC transporters.

PMID- 15237862
TI  - A look at an interactive classroom-based drug abuse prevention program:
      interactive contents and suggestions for research.
AB  - Interactivity has been shown to be a critical element of effective drug abuse
      prevention programs. This study examined the contents of Project Towards No Drug
      Abuse, a program that has revealed strong effects only when delivered in a highly
      interactive version. Types of teacher and student interactive messages were
      identified. It is speculated that explicit action on the part of the teacher to
      have students make statements and ask questions of one another may be the essence
      of effective drug education program delivery. Suggestions for future research on
      interactivity were made.

PMID- 15237863
TI  - Substance use, self-esteem, and depression among Asian American adolescents.
AB  - The relationship of self-esteem and depression with alcohol, tobacco, and other
      drug (ATOD) use was tested in a California statewide sample of more than 4,300
      Asian American high school students comprising five subgroups: Chinese, Japanese,
      Korean, Filipino, and Vietnamese. Estimated prevalence rates of alcohol, tobacco,
      and marijuana use among males and females from these Asian American subgroups are
      presented. Correlations revealed that cigarette, alcohol, and marijuana use were
      generally more related to high depression and low self-esteem in females than in
      males. Logistic regression analysis with only the female subjects investigated
      whether the relationship between the psychological variables and ATOD use was
      maintained even after controlling for traditionally important constructs in ATOD
      use (grade level in school, born in the United States, ethnicity, and ATOD use by
      friends). These results indicated that for females, depression was significantly
      related to alcohol and tobacco use, but self-esteem was not. Neither self-esteem
      nor depression was a significant contributor to marijuana use. Issues related to
      the application of these results are discussed.

PMID- 15237864
TI  - Low emotional intelligence as a predictor of substance-use problems.
AB  - This study explored the relationship between low emotional intelligence and
      substance-use problems in adults. One hundred and forty-one participants
      completed the Self-Administered Alcoholism Screening Test, the Drug Abuse
      Screening Test, an emotional intelligence scale, and a measure of psychosocial
      coping. Low emotional intelligence was a significant predictor of both alcohol
      related problems and drug-related problems. Poorer coping predicted drug-related
      problems, but not alcohol-related problems. Coping was not found to be a
      significant mediator between emotional intelligence and substance-use problems.
      Possible implications for intervention and treatment efforts are discussed.

PMID- 15237865
TI  - Adolescent and adult alcohol attitudes in a high alcohol consumption community.
AB  - The study examines alcohol-related attitudes among adolescents and adults in a
      high consumption community, exploring whether adolescents and adults hold similar
      or different views regarding adolescent drinking. Data were gathered from adults
      in a Midwestern city via random telephone survey of 487 adults (30% with children
      under the age of 21). Students in grades 6-12 (n = 558) also completed a youth
      version of the survey in classrooms. Results indicated that becoming a parent was
      associated with more restrictive attitudes about adolescent alcohol use,
      regardless of the age of their children. Adolescents aged 14 to 17 had the least
      restrictive attitudes. Adults aged 18 to 24 (who were not parents) reported
      values similar to older adolescents. Younger adolescents, while similar to older
      adolescents in perception of community alcohol problems, were more like parents
      and older adults in attitudes about adolescent drinking. Both adolescents and
      adults greatly overestimated actual amounts of community adolescent binge
      drinking.

PMID- 15237866
TI  - Beliefs and social norms about codeine and promethazine hydrochloride cough syrup
      (CPHCS) onset and perceived addiction among urban Houstonian adolescents: an
      addiction trend in the city of lean.
AB  - In the current study, we used a qualitative approach to investigate relevant
      beliefs and norms associated with codeine and promethazine hydrochloride cough
      syrup (CPHCS) consumption, initiation, and perceived addiction among 48
      alternative school students who identified themselves as current CPHCS users. In
      general, both boys and girls believed that CPHCS addiction started during an
      individual's initial consumption. A majority of both groups reported that their
      second CPHCS event was initiated during the same or next day after their first
      event. Our findings suggest that friends and an innovative form of hip-hop music
      called "screw" are strong reinforcers of CPHCS use.

PMID- 15237867
TI  - Young adolescents, tobacco advertising, and smoking.
AB  - BACKGROUND: In adolescents aged 12-14, we measured attitudes to tobacco
      advertising. Our purpose is to understand the relation of these attitudes to
      tobacco use and identify the groups most influenced by the advertising. METHODS:
      Survey of adolescents on Gran Canaria Island, Spain, about aspects of family,
      school, peers, tobacco consumption, and tobacco advertising. The subjects of the
      double-stratified cluster sample were 1910 students at the same grade level in 33
      schools; 86.6% were 13 or 14 years old, and 51.2% were boys. We generated
      measures for attitudes to tobacco advertising from replies to seven questions
      with ordinal scales by an analysis of categorical principal components. To relate
      attitude to tobacco advertising and the profiles of these adolescents, we used
      multiple regression and logistic regression models. RESULTS: Attitudes to tobacco
      advertising are related to some home and school factors, but most significantly
      to tobacco and alcohol consumption, to amount of time at home without adults, and
      to peer influence. CONCLUSIONS: It is possible to draw up profiles of the
      students most vulnerable to tobacco advertising, and to cluster them in two
      groups, the "vitalists" and the "credulous." The effect of cigarette ads is
      different between these groups. This study can help to orientate smoking
      prevention.

PMID- 15237868
TI  - Jocks, gender, race, and adolescent problem drinking.
AB  - Alcohol remains the drug of choice for many adolescents; however, the nature of
      the relationship between athletic involvement and alcohol misuse remains
      ambiguous. In this article, we used a longitudinal sample of over 600 Western New
      York adolescents and their families to explore the gender-specific and race
      specific relationships between identification with the "jock" label and
      adolescent alcohol consumption, specifically problem drinking. Operationalization
      of problem drinking included frequency measures of heavy drinking, binge
      drinking, and social problems related to alcohol (e.g., trouble with family,
      friends, school officials over drinking). Self-identified adolescent "jocks" were
      more likely to engage in problem drinking than their non-jock counterparts, even
      after controlling for gender, age, race, socioeconomic status, physical maturity,
      social maturity, and frequency of athletic activity. Jock identity was strongly
      associated with higher binge drinking frequency in Black adolescent girls. This
      study underscores the need to distinguish between objective and subjective
      meanings of athletic involvement when assessing the relationship between sport
      and adolescent health-risk behavior.

PMID- 15237869
TI  - Appropriatech: prosthodontics for the many, not just for the few.

PMID- 15237870
TI  - Misfit and functional loading of craniofacial implants.
AB  - PURPOSE: This study sought to develop an understanding of the magnitude and types
      of loads generated on craniofacial implants supporting an auricular prosthesis.
      MATERIALS AND METHODS: Strain gauges were used to measure the in vitro and in
      vivo misfit loads generated when connecting auricular-style superstructures to
      implants and the in vivo functional load generated during the removal and
      insertion of the auricular prostheses. In addition, the vertical misfit of the 11
      custom-built two-implant superstructures used in the in vitro study was measured.
      RESULTS: Superstructures used in the in vitro study that were considered
      clinically passive still had considerable preloads. In addition, the calibrated
      loads, which would result from the vertical misfit alone, did not account for the
      magnitude of the generated preloads. CONCLUSION: The clinical definition of
      misfit based on vertical distortion of the superstructure did not quantify the
      resulting misfit load. Measured in vivo functional loads were smaller than the
      misfit loads.

PMID- 15237871
TI  - Altered jaw posture and occlusal disruption patterns following mandibular
      advancement therapy for sleep apnea: a preliminary study of cephalometric
      predictors.
AB  - PURPOSE: Reports of irreversible alteration in jaw posture and destructive
      occlusal contact relationships in individuals using mandibular advancement
      devices for obstructive sleep apnea are beginning to appear. This study sought
      cephalometric means of identifying such individuals before commencing therapy.
      MATERIALS AND METHODS: Cephalograms of 34 obstructive sleep apnea sufferers who
      had worn mandibular advancement devices for 2 years were compared retrospectively
      with baseline films taken at commencement of therapy and analyzed for signs of
      morphologic changes in jaw position and occlusal relationship. In affected
      patients, two distinct morphologic species of mandibular reposturing became
      evident: (1) bilateral posterior open bite with destructive incisal attrition;
      and (2) less destructive intermediate open bite over the premolar and first molar
      regions. From the observed morphology patterns, gonial angle and maxillary
      mandibular plane angle were analyzed as possible vertical cephalometric risk
      predictors, with newly defined pterygoid advancement proportion (PtAP) as a
      horizontal predictor. RESULTS: Three patients displayed the posterior open bite
      pattern and had gonial angles < or = 119 degrees and maxillary-mandibular plane
      angles < or = 16 degrees, with PtAP values > or = 0.48. Prediction intervals for
      the five intermediate open bite cases were 118 degrees < or = gonial angle < or =
      128 degrees, and 23 degrees < or = maxillary-mandibular plane angle < or = 32
      degrees. PtAP values were > or = 0.52. CONCLUSION: Cephalometric analysis can
      help practitioners identify which apnea patients might be likely to develop
      irreversible mandibular postural changes from wearing a jaw-repositioning device.

PMID- 15237872
TI  - A literature review of two-unit cantilevered FPDs.
AB  - PURPOSE: This review article evaluated the clinical performance of two-unit
      cantilevered, single-abutment, single-pontic, resin-bonded fixed partial dentures
      (FPDs) by comparing them to noncantilevered resin-bonded FPDs with two abutments
      and a single pontic. MATERIALS AND METHODS: One publication on design principles
      and 11 clinical research studies were selected by searching two databases.
      RESULTS: Six of the studies dealt exclusively with two-unit cantilevered resin
      bonded FPDs, and five studies compared fixed-fixed design resin-bonded partial
      dentures with cantilevered resin-bonded FPDs. Two-unit cantilevered resin-bonded
      FPDs for single-tooth replacement appear to be reliable and predictable
      restorations, provided their preparations meet the right standards. CONCLUSION:
      According to the studies reviewed, two-unit cantilevered FPDs show better
      longevity than resin-bonded fixed-fixed partial dentures in similar situations.

PMID- 15237873
TI  - Experimental zirconia abutments for implant-supported single-tooth restorations
      in esthetically demanding regions: 4-year results of a prospective clinical
      study.
AB  - PURPOSE: This prospective clinical study evaluated an experimental implant
      abutment made of densely sintered zirconia with respect to peri-implant hard and
      soft tissue reaction as well as fracture resistance over time. MATERIALS AND
      METHODS: Twenty-seven consecutively treated patients with 54 single-tooth
      implants were included. Zirconia abutment ingots were individually shaped and set
      on the implants with gold screws. All-ceramic (Empress I) crowns were cemented
      using a composite cement. At the 1- and 4-year examinations, reconstructions were
      evaluated for technical problems (fracture of abutment or crown, loosening of
      abutment screw). Modified Plaque and simplified Gingival Indices were recorded at
      implants and neighboring teeth, and peri-implant bone levels were
      radiographically determined. RESULTS: All but 1 of the 27 patients with 53
      restorations could be evaluated at 1 year, and 36 restorations in 18 patients
      were evaluated 4 years after abutment and crown insertion. The median observation
      period for the reconstructions was 49.2 months. No abutment fractures occurred.
      Abutment screw loosening was reported for 2 restorations at 8 months and 27
      months, respectively. Mean Plaque Index was 0.4 (SD 0.6) at abutments and 0.5 (SD
      0.6) at teeth; mean Gingival Index was 0.7 (SD 0.5) at abutments and 0.9 (SD 0.5)
      at teeth. Mean marginal bone loss measured 1.2 mm (SD 0.5) after 4 years of
      functional loading. CONCLUSION: Zirconia abutments offered sufficient stability
      to support implant-supported single-tooth reconstructions in anterior and
      premolar regions. The soft and hard tissue reaction toward zirconia was
      favorable.

PMID- 15237874
TI  - Prosthetic restoration following removal of chondrosarcoma in the premaxillary
      region: a case presentation and follow-up for 16 years.
AB  - PURPOSE: The present report describes a relatively simple but effective
      prosthodontic treatment following removal of a moderately well differentiated
      osteogenic chondrosarcoma in the premaxillary region. MATERIALS AND METHODS:
      Following removal of a rare tumor, a young man was treated with gold crowns on
      three molars and a metal-ceramic crown on a first premolar, with attachments in
      the areas facing the defect for esthetic reasons. A removable partial denture was
      retained by the attachments and conventional cast retentive circumferential
      clasps, including a hollow obturator filling the defect. RESULTS: The restoration
      has served the patient for 16 years, seemingly without discomfort, and it has not
      required any maintenance. The patient has kept up with his oral hygiene, using
      conventional methods for the teeth and prosthesis, with periodic flushing with
      chlorhexidine solution. He has lived a normal family life and finished his
      university education. CONCLUSION: The problem-free use of the appliance can be at
      least partly explained by the patient taking oral hygiene measures seriously from
      the beginning. This report explains how relatively uncomplicated prosthodontic
      measures can enormously affect quality of life.

PMID- 15237875
TI  - Effect of surface treatment on the bonding of an autopolymerizing soft denture
      liner to a denture base resin.
AB  - PURPOSE: This in vitro study evaluated the effects of surface treatments and
      thermocycling on the bonding of autopolymerizing silicone soft denture liner
      (Sofreliner) to denture base resin. MATERIALS AND METHODS: The bonding surfaces
      of denture base cylinders were polished with 600-grit silicon carbide paper and
      pretreated with applications of Sofreliner Primer, Sofreliner Primer after air
      abrasion, Reline Primer, or Reline Primer after air abrasion. Failure loads and
      elongation at failure were measured after subjecting specimens to 0, 10,000,
      20,000, and 30,000 thermocycles. Failure modes were assessed for all specimens.
      Seven specimens were fabricated for each of 16 groups, including four
      pretreatments and four thermocycle groups. RESULTS: Failure loads of the
      Sofreliner Primer group were significantly higher than those of the air-abrasion
      group up to 20,000 thermocycles; both groups showed cohesive failures of the soft
      denture liner. Failure loads of the Reline Primer group were significantly higher
      than with Reline Primer after air abrasion up to 10,000 thermocycles. Failure
      mode after 10,000 thermocycles was cohesive for the Reline Primer group and mixed
      cohesive/adhesive for Reline Primer after air abrasion. Failure loads of the
      Sofreliner Primer group were significantly higher than those of the Reline Primer
      group at each thermocycling interval. Elongation values decreased after 10,000
      thermocycles for all groups. CONCLUSION: Air abrasion on the denture base resin
      surface was not effective in enhancing failure load. Cyclic thermal stress is one
      factor degrading the bond between soft denture liner and acrylic resin denture
      base.

PMID- 15237876
TI  - Five-year evaluation of two resin-retained ceramic systems: a retrospective study
      in a general practice setting.
AB  - PURPOSE: This study performed a clinical evaluation of two ceramic systems
      retained with resin-bonded cement, observed clinical outcomes over time, and
      compared the two systems used (IPS Empress and Vitadur Alpha) and differences
      between inlays and onlays. MATERIALS AND METHODS: Three general practitioners
      placed 317 restorations (215 IPS Empress and 102 Vitadur Alpha) in 153 patients.
      The first clinical registration was performed 6 to 36 months after placement of
      the restorations by calibrated investigators using the CDA criteria. A second
      follow-up was performed 36 months later. The mean time in function for all
      restorations at follow-up was 60 months. RESULTS: At the first examination, five
      restorations were not clinically acceptable because of fractures and caries. At
      follow-up, another 16 restorations were judged as failures. The most significant
      changes over time were an increase in rough surfaces, evidence of increasing
      marginal discrepancy, and slight mismatch in color between restored tooth and
      ceramic restoration. When comparing IPS Empress to Vitadur Alpha, there was no
      difference in clinical performance. When comparing inlay and onlay restorations,
      there was a tendency toward a higher number of failures in the inlay group. The
      overall success rate was 92%. CONCLUSION: Ceramic restorations performed well
      after 5 years in function and provide a good treatment alternative that can be
      successfully managed in general dental practice.

PMID- 15237877
TI  - Retention and failure morphology of prefabricated posts.
AB  - PURPOSE: This study evaluated the effect of cement, post material, surface
      treatment, and shape (1) on the retention of posts luted in the root canals of
      extracted human teeth and (2) on the failure morphology. MATERIALS AND METHODS:
      Posts of titanium alloy (ParaPost XH), glass fiber (ParaPost Fiber White), and
      zirconia (Cerapost) received one of several surface treatments-sandblasting,
      CoJet treatment, application of Metalprimer II, or sandblasting followed by
      silane application-and were then luted in the prepared root canal of human
      incisors and canines (n = 10). Following water storage at 37 degrees C for 7
      days, retention was determined by extraction of the posts. Failure morphology of
      extracted posts was analyzed and quantified stereomicroscopically. RESULTS: Type
      of luting cement, post material, and shape of post influenced the retention and
      failure morphology of the posts. Because of limited adherence of the cement to
      the root canal, surface treatments did not always have a positive effect on
      retention. CONCLUSION: Choice of luting cement was critical for all three types
      of posts. Parallel posts showed superior retention to tapered posts.

PMID- 15237878
TI  - Fatigue resistance of teeth restored with cuspal-coverage composite restorations.
AB  - PURPOSE: This study assessed the influence of palatal cuspal coverage on the in
      vitro fatigue resistance and failure mode of Class II resin composite
      restorations including replacement of the buccal cusp in premolars. MATERIALS AND
      METHODS: A master model was made of a maxillary premolar with an MOD amalgam
      cavity and a simulated fracture of the buccal cusp from the isthmus floor to the
      CEJ. Using a copy-milling machine, this preparation was copied to 20 extracted
      human maxillary premolars (group A). Subsequently, the palatal cusp was reduced
      by 1.5 mm; this modified preparation was copied to 20 additional maxillary
      premolars (group B). Direct resin composite restorations were made in all teeth.
      Cyclic load (5 Hz) was applied, starting with a load of 200 N (10,000 cycles),
      followed by stages of 400, 600, 800, and 1,000 N at a maximum of 50,000 cycles
      each. Samples were loaded until fracture or to a maximum of 210,000 cycles.
      RESULTS: Of the restored premolars of group A, 20% withstood all 210,000 loading
      cycles; in group B, this figure was 55%. In group A, 19% of the fractures ended
      below the CEJ; in group B, 78% did. CONCLUSION: Palatal cuspal coverage increased
      the fatigue resistance of Class II resin composite restorations with replacement
      of the buccal cusp in premolars. However, fractures of restorations with cuspal
      coverage led to more dramatic failures that made restoration virtually
      impossible. This suggests caution in lowering remaining cusps for these adhesive
      restorations in the clinical situation.

PMID- 15237879
TI  - Effect of glass-fiber reinforcement and water storage on fracture toughness (KIC)
      of polymer-based provisional crown and FPD materials.
AB  - PURPOSE: The effect of glass-fiber reinforcement and water storage on the
      fracture toughness (KIC) of polymer-based provisional crown and fixed partial
      denture (FPD) materials was investigated. MATERIALS AND METHODS: Five
      unreinforced single-edged, notched control specimens and five test specimens
      reinforced with unidirectional E-glass fibers (Stick) were fabricated from three
      dimethacrylate-based provisional materials and one monomethacrylate-based
      provisional material. The specimens were stored in water at 37 degrees C for 1,
      7, 30, or 60 days. Specimens were loaded in three-point bending at a cross-head
      speed of 0.1 mm/s. Mode I plane-strain KIC was calculated using the maximum load,
      and results of the two groups were compared. The water storage effect on KIC with
      time was also evaluated. RESULTS: The KIC of provisional materials reinforced
      with glass fibers (range 7.5 to 13.8 MNm(-1.5)) was significantly higher than
      that of unreinforced materials (range 1.3 to 3.1 MNm(-1.5)), by a factor of 4.4
      to 5.5. A small, gradual decrease of KIC in reinforced specimens occurred with
      aqueous storage, but it was not statistically significant. CONCLUSION: The KIC of
      polymer-based provisional crown and FPD materials was significantly increased
      when they were reinforced with unidirectional E-glass fibers. Water storage for
      up to 2 months still left the reinforced materials with KIC values in excess of 7
      MNm(-1.5). Hence, their performance was satisfactory.

PMID- 15237880
TI  - Long-term survival of porcelain laminate veneers using two preparation designs: a
      retrospective study.
AB  - PURPOSE: This study evaluated the long-term survival of anterior porcelain
      laminate veneers placed with and without incisal porcelain coverage. MATERIALS
      AND METHODS: Two prosthodontists in a private dental practice placed 110 labial
      feldspathic porcelain veneers in 50 patients; 46 veneers were provided with
      incisal porcelain coverage, and 64 were not. The veneers were evaluated
      retrospectively from case records for up to 7 years (mean 4 years). RESULTS: At
      5, 6, and 7 years, the cumulative survival estimates were 95.8% for veneers with
      incisal porcelain coverage and 85.5% for those without incisal coverage. The
      difference was not statistically significant. Six of the nine failures occurred
      from porcelain fracture in the veneers without incisal coverage. CONCLUSION:
      Although there was a trend for better long-term survival of the veneers with
      incisal porcelain coverage, this finding was not statistically significant.

PMID- 15237881
TI  - Color distribution and visual color assessment of human gingiva and mucosa: a
      systematic review of the literature.
AB  - PURPOSE: This study undertook a systematic overview of the literature on the
      description and visual measurement of gingival color. MATERIALS AND METHODS: Two
      research questions were formulated. The first addressed the description of
      gingival color, while the second aimed at visual color measurement techniques. An
      electronic search was performed in 22 literature databases. The electronic search
      was complemented by hand searching. The retrieved articles were independently
      reviewed by two members of the research team. The levels of evidence of the
      articles were classified following the guidelines of the Oxford Centre for
      Evidence-Based Medicine. RESULTS: Of the nine articles retrieved by the two
      searches, six applied to the first question, two applied to the second question,
      and one applied to both questions. Three articles were published in Japanese and
      dealt with the color of gingival and alveolar mucosa. The clinical studies showed
      that the intraoral tissues of younger persons are of a lighter color. Evidence
      levels were no higher than 4. CONCLUSION: Studies on the description of gingival
      color used a narrative approach. Studies on visual gingival color measurement had
      diverse aims, methods, and parameters. It is impossible to compare or even
      combine their outcomes in a scientifically meaningful manner. Since none of the
      investigations used a controlled or randomized design, they represent low levels
      of evidence.

PMID- 15237883
TI  - Cytotoxicity of denture base resins: effect of water bath and microwave
      postpolymerization heat treatments.
AB  - PURPOSE: This study compared the effect of two postpolymerization heat treatments
      on the cytotoxicity of three denture base resins on L929 cells using 3H-thymidine
      incorporation and MTT assays. MATERIALS AND METHODS: Sample disks of Lucitone
      550, QC 20, and Acron MC resins were fabricated under aseptic conditions and
      stored in distilled water at 37 degrees C for 48 hours. Specimens were then
      divided into three groups: (1) heat treated in microwave oven for 3 minutes at
      500 W; (2) heat treated in water bath at 55 degrees C for 60 minutes; and (3) no
      heat treatment. Eluates were prepared by placing three disks into a sterile glass
      vial with 9 mL of Eagle's medium and incubating at 37 degrees C for 24 hours. The
      cytotoxic effect from the eluates was evaluated using the 3H-thymidine
      incorporation and MTT assays, which reflect DNA synthesis levels and cell
      metabolism, respectively. RESULTS: The components leached from the resins were
      cytotoxic to L929 cells when 3H-thymidine incorporation assay was employed. In
      contrast, eluates from all resins revealed noncytotoxic effects as measured by
      MTT assay. For both MTT assay and 3H-thymidine incorporation, the heat treatments
      did not decrease the cytotoxicity of the materials tested. CONCLUSION: Resins
      were graded by 3H-thymidine incorporation assay as slightly cytotoxic and by MTT
      assay as noncytotoxic. Cytotoxicity of the denture base materials was not
      influenced by microwave or water bath heat treatment.

PMID- 15237882
TI  - Risk factors for high occlusal wear scores in a population-based sample: results
      of the Study of Health in Pomerania (SHIP).
AB  - PURPOSE: Using a population-based sample of the cross-sectional epidemiologic
      "Study of Health in Pomerania" (SHIP), this study evaluated whether certain
      occlusal and sociodemographic factors besides age and gender are risk factors for
      high dental wear. MATERIALS AND METHODS: Medical history and dental and
      sociodemographic parameters of 2,529 dentate subjects selected representatively
      and according to age distribution were checked for correlations with the
      occurrence of high occlusal wear symptoms using a multivariate logistic
      regression model. Occlusal wear was recorded using the attrition index by Ekfeldt
      et al and was age adjusted by determining high occlusal wear for every 10-year
      age group as index values > or = 90th percentile. RESULTS: The following
      independent variables were found to be correlated with high occlusal wear: male
      gender, odds ratio 2.2; frequent bruxism, odds ratio 2.5; loss of molar occlusal
      contact (Eichner classification), odds ratio from 1.5 to 3.1; edge-to-edge
      relation of incisors, odds ratio 1.7; unilateral buccolingual cusp-to-cusp
      relation, odds ratio 1.8; and unemployment, odds ratio 1.6. In contrast, anterior
      cross-bite, unilateral posterior cross-bite, and anterior crowding were
      protective for high occlusal wear levels, as shown by significantly reduced odds
      ratios. Gender-separated analysis showed that self-reported bruxism was a risk
      factor only for men. CONCLUSION: In addition to some occlusal factors, the main
      factors associated with occlusal wear were bruxism and gender.

PMID- 15237884
TI  - Innovative gas injection technique for closed-hollow obturator.
AB  - PURPOSE: The purpose of this study was to determine the proper prerequisite
      conditions for gas injection and the steps for applying gas injection for
      obturator fabrication. MATERIALS AND METHODS: Optimal prerequisite conditions
      were investigated by using thermocoupling to verify exothermic changes in the
      resin during polymerization. Three experimental groups were designated: in the
      control group (C), resin was packed into the mold without argon gas injection; in
      the gas injection group (GI), after resin packing, gas was injected into the
      resin bulb in the mold; and in the plunger/gas injection group (PGI), after resin
      packing, the syringe plunger was drawn out before gas injection. RESULTS: The 55
      degrees C mold temperature and addition of 0.3% DMPT to the monomer liquid caused
      differences in exothermic temperature increase in various parts of the resin.
      Without gas injection and plunger drawing, porosity was observed in the thick
      bulbs of groups C and PGI. In group PGI, a balloon-like elliptic hollow was
      observed. Compared to group C, the weight reduction in group PGI was
      approximately 10%. CONCLUSION: Proper mold temperature with secondary venting and
      the addition of DMPT were required before the injection of gas. The resulting
      prosthesis could be fabricated in one step and required no resin seal.

PMID- 15237886
TI  - A study of the physical and chemical properties of four resin composite luting
      cements.
AB  - PURPOSE: This study evaluated the surface microhardness and flexural and
      compressive strengths of five luting cements and compared the degree of
      conversion of dual and autopolymerized forms of four resin-based luting cements.
      MATERIALS AND METHODS: Four resin composite luting cements-Panavia F, Variolink
      2, RelyX Unicem Applicap, and RelyX ARC-and a polycarboxylate cement (Durelon,
      control group) were used in three-point bending, compression, and Vickers
      hardness tests following water storage for 1 week. Resin composite cements were
      additionally investigated with both dual and autopolymerization techniques under
      Fourier transformed infrared spectroscopy. Differences were analyzed using one
      way ANOVA. RESULTS: The highest flexural strengths were obtained with Variolink 2
      (90 MPa, SD 22), whereas the lowest were observed with Durelon (28 MPa, SD 4).
      RelyX Unicem showed the highest hardness values (44 HV, SD 5), whereas Variolink
      2 gave the lowest (32 HV, SD 6). The highest compressive strengths were obtained
      with RelyX Unicem (145 MPa, SD 32), whereas the lowest were observed with Durelon
      (41 MPa, SD 17). For both dual and autopolymerized groups, RelyX ARC showed the
      highest degrees of conversion (81% and 61%, respectively) and RelyX Unicem had
      the lowest (56% and 26%, respectively). CONCLUSION: Resin composite luting
      cements of similar chemical characterizations differed in their physical
      properties, and polymerization method influenced their degree of conversion.

PMID- 15237885
TI  - Differential wear of teeth and restorative materials: clinical implications.
AB  - PURPOSE: This study reviewed the wear of commonly used dental restorative
      materials and their effects on the opposing dentition. MATERIALS AND METHODS: Key
      words were used with PubMed to retrieve pertinent references to publications on
      tooth and restoration wear. RESULTS: The wear resistance of newer esthetic
      restorative materials has generally improved, and the damage caused by several
      materials to the opposing dentition has been reduced. However, the different
      structures and physical properties of tooth substance and restorative materials
      will eventually lead to varying degrees of differential wear. The extent and rate
      of wear are influenced by many intraoral factors. CONCLUSION: Selection of
      restorative materials must be based on knowledge of their wear behavior and the
      individual needs of each patient. The lowest wear rates for restorations and the
      opposing dentition occur with metal alloys, machined ceramics, and microfilled
      and microfine hybrid resin composites.

PMID- 15237887
TI  - Adhesive strength between fiber-reinforced composites and veneering composites
      and fracture load of combinations of these materials.
AB  - PURPOSE: This study examined the influence of the adhesive strength between fiber
      reinforced composites (FRC) and veneering composites on the fracture load of
      combinations of these materials. MATERIALS AND METHODS: Six materials were used.
      An experimental material called BR-100, Vectris, and FibreKor were the types of
      FRC. Estenia, Targis, and Sculpture were used as veneering composites. With the
      Estenia/BR-100 combination, the surface of the FRC was subjected to three
      different conditions before veneering. Ten specimens of each combination were
      fabricated and divided into two groups: One group was stored in 37 degrees C
      distilled water for 24 hours, and the other was thermocycled (4 degrees C/60
      degrees C, 10,000 cycles). Adhesive strength between FRCs and veneering
      composites was determined using the compressive shear strength test. In addition,
      fracture loads of laminate specimens were determined. RESULTS: Good adhesive
      strength was obtained by leaving an unpolymerized layer on the surface of the FRC
      or by performing silane and bonding treatment. In the Estenia/BR-100 combination,
      when the adhesive strength was low, the fracture load of the laminate specimens
      was also low. However, the difference in fracture load was not as large as that
      seen in adhesive strength. The fracture load of each laminate specimen was
      significantly lower after thermocycling. CONCLUSION: The adhesive strength
      between the FRCs and veneering composite had an effect on the fracture load of
      the combination.

PMID- 15237888
TI  - A literature review on the prosthetic treatment of structurally compromised
      teeth.
AB  - PURPOSE: This article presents a review of the literature on biomechanical
      factors affecting the treatment outcome of prosthetic treatment of structurally
      compromised dentitions, with the main emphasis on often-compromised
      endodontically treated teeth. MATERIALS AND METHODS: Articles cited in a
      MEDLINE/PubMed search were reviewed with a focus on factors influencing the risk
      for fatigue failures. RESULTS: Technical failures in connection with fixed
      prosthodontics are often caused by fatigue fractures. The abutments, cement, and
      reconstruction are all subjected to stress caused by occlusal forces, and fatigue
      fracture may occur at the weakest point or where the maximum stress occurs. The
      weakest point is frequently in connection with endodontically treated teeth
      restored with posts and cores. CONCLUSION: The literature points to nonaxial
      forces as a risk for fatigue fracture of teeth, cement, and restorative material.
      Favorable occlusal prosthesis design is probably more important for survival of
      structurally compromised endodontically treated teeth than is the type of post
      used.

PMID- 15237889
TI  - Arthur R. Frechette Research Award in Prosthodontics.

PMID- 15237890
TI  - Radiologic case study. Complete radiocarpal dislocation with an associated radial
      styloid fracture.

PMID- 15237891
TI  - Intramedullary nailing in elderly patients.

PMID- 15237892
TI  - Innovation in sports medicine.

PMID- 15237893
TI  - Posterior capsular repair following total hip arthroplasty: a modified technique.
AB  - Various techniques of posterior capsular repair following THA have been reported
      and studies have demonstrated the merits of posterior capsular repair with
      respect to decreasing the incidence of dislocation. Our modified technique using
      three sutures offers excellent fixation of the hip capsule on the greater
      trochanter. The small drill holes needed for the #2 Fiberwire minimize the risk
      of a greater trochanteric fracture through the drill holes and osteoporotic bone.
      To date, we have not experienced any complications or reaction to this material.
      The importance of a posterior capsule repair has been well documented in the
      literature. A rigid capsular repair can prevent excess internal rotation and
      therefore minimize the incidence of postoperative dislocation following THA.

PMID- 15237894
TI  - Articular reconstruction of osteochondral defects of the talus through autologous
      chondrocyte transplantation.

PMID- 15237895
TI  - Methicillin-resistant staphylococcal infections: an important consideration for
      orthopedic surgeons.
AB  - Postoperative infections in joint prostheses and fracture-fixation devices
      commonly involve both MRSA and methicillin resistant coagulase-negative
      staphylococcus. In addition, community-acquired MRSA has also become an important
      consideration when infected patients are admitted to the hospital from the
      community. Preoperative colonization with MRSA and methicillin resistant
      coagulase-negative staphylococcus increases the risk of postoperative surgical
      site infections in orthopedic patients. Up to 5.3% of orthopedic patients are
      colonized with these organisms on hospital admission. Screening and
      decolonization of methicillin resistant staphylococci decrease the incidence of
      postoperative surgical site infections in the orthopedic patient. This may be
      particularly important in orthopedic implants given the difficulty encountered in
      treating infected prosthesis. Current US guidelines advocate screening for
      methicillin resistant staphylococci only when risk factors are present. Growing
      evidence suggests that screening and decolinization of all patients having
      elective orthopedic procedures, especially those including prosthetic implants,
      will decrease the incidence of postoperative infections. The infected prosthesis
      may be potentially salvaged if the clinical manifestations of infection have been
      present for < or = 10 days, the implant is stable, and the etiologic organisms
      are susceptible to oral antibiotics.

PMID- 15237896
TI  - Arthroscopic rotator cuff repair.

PMID- 15237897
TI  - Management of acute Achilles tendon ruptures.

PMID- 15237898
TI  - Stress fractures in athletes: risk factors, diagnosis, and management.

PMID- 15237899
TI  - In-hospital outcome and resource use in hip arthroplasty: influence of body mass.
AB  - To determine the influence of body mass index (BMI) on perioperative morbidity,
      functional recovery, and hospital use, the records of 207 patients who underwent
      primary total hip arthroplasty were reviewed and patients were grouped according
      to BMI. Transfusion requirements, operative complications, functional recovery,
      and assistance needed for transfers from supine to sit, sit to stand, and bed to
      chair positions were analyzed at the first physical therapy. Compared with
      others, morbidly obese patients (BMI > or = 40 kg/m2) had significantly longer
      mean operative time and higher mean intraoperative blood loss (P<.05), a trend
      toward more complications, but no significant difference in functional recovery
      and hospital use.

PMID- 15237900
TI  - Functional assessment using the step-up-and-over test and forward lunge following
      ACL reconstruction.
AB  - This investigation compared lower extremity function of a control group and a
      group of patients who underwent anterior cruciate ligament (ACL) reconstruction
      using a repeated measures post-test only control group design. The ACL
      reconstruction group consisted of 18 patients at least 6 months postoperative
      (mean 58+/-19 weeks) and the control group consisted of 18 healthy,
      recreationally active individuals. Both groups performed a step-up-and-over test
      and a forward lunge on a long force plate. During the step-up-and-over test, the
      control group produced significantly more force during the initial step than the
      ACL reconstruction group. Also, when the ACL reconstruction patients led with the
      involved extremity, they were significantly slower. During the forward lunge
      test, the impact index and force impulse measurements were significantly greater
      for the uninvolved leg than the involved leg in the ACL reconstruction group. The
      implications are that force generation during functional tests may remain
      compromised for >1 year following reconstruction. The aforementioned tests are
      promising for evaluation of function following ACL reconstruction.

PMID- 15237901
TI  - Preoperative evaluation of adult isthmic spondylolisthesis with diskography.
AB  - Fourteen consecutive patients with a diagnosis of isthmic spondylolisthesis
      (grade I and II) underwent provocative lumbar diskography (L2-S1) to evaluate the
      disk adjacent to the spondylolisthesis. Seven (50%) of 14 patients had concordant
      pain at the disk above the slip and 2 patients had no pain at the slip level.
      Surgical treatment included anteroposterior fusion of the slip level and any
      adjacent concordant levels. Clinical results included 3 excellent, 7 good, 2
      fair, and 1 poor outcome. This data supports the hypothesis that the disk
      adjacent to an isthmic slip is predisposed to symptomatic degeneration in the
      adult patient with axial pain. It does not prove that a fusion is indicated or
      that clinical outcomes would be improved with this approach.

PMID- 15237902
TI  - Managing anterior shoulder instability with bracing: an expanded update.
AB  - This article provides an updated report on functional bracing for anterior
      shoulder instability. A classification of shoulder braces is reintroduced into
      three separate types. Type A braces limit shoulder motion to a "safe zone,"
      whereas types B and C apply indirect and direct stabilizing forces to the joint,
      respectively. Thirteen of the most widely available braces were surveyed and the
      parameters of comfort, convenience, construction, cost, potential sport use, and
      special features were analyzed. Problem areas included poor fit and range of
      motion restriction. The system of classifying sports based on shoulder demands is
      reintroduced.

PMID- 15237903
TI  - Syringomyelia in a college football player with motor weakness and paresthesias.

PMID- 15237904
TI  - Combined treatment of primary hydatid disease of the vastus lateralis muscle.

PMID- 15237905
TI  - Ossification of the posterior longitudinal ligament associated with rheumatoid
      arthritis.

PMID- 15237906
TI  - [In defense of education and post-graduate research in allergy and clinical
      immunology].

PMID- 15237907
TI  - [Use of alternative medicine in the treatment of allergic diseases].
AB  - BACKGROUND: The alternative medicine and the complementary medicine are forms of
      treatment very spread and frequently demanded by patients with allergic diseases.
      According to recent studies, homeopathy, acupuncture and herbal medicine are the
      most commonly used types of alternative medicine. OBJECTIVE: To know the
      frequency in the use of different types of alternative medicine for the treatment
      of allergic diseases in patients attended at the Centro Regional de Alergia e
      Immunologia Clinica of the Hospital Universitario de Monterrey, Nuevo Leon.
      MATERIAL AND METHODS: A transversal, descriptive and observational study was done
      by the use of questionnaires applied to patients and/or patients' relatives
      attended in this Center. This survey included questions to focus the
      investigation in the use of a Iternative medicine for the treatment of any
      allergic disease. The data analysis was done by descriptive statistics. RESULTS:
      Four hundred one questionnaires were applied. The average age of the patients was
      of 14 years (range from 1 to 73 years). Fourty-seven percent (189 patients) were
      female and 58.2% (212 patients) were male. The diagnoses included: allergic
      rhinitis in 215 patients (53.6), asthma in 97 (24.2%), rhinitis and asthma in 73
      (18.2) and atopic dermatitis in 16 (4%). Out of the patients 34.4% (138) had used
      at least one type of alternative medicine for the treatment of their allergic
      disease. Homeopathy was the most commonly used type of alternative medicine
      (78.2%), followed by the natural medicine (31.5%). CONCLUSIONS: Alternative
      medicine for the treatment of allergic diseases is frequent in patients who
      attend to this center. Homeopathy and the natural medicine are the most used.

PMID- 15237908
TI  - [Clinical characteristics of atopic dermatitis in a group of patients attending
      to the Regional Center of Allergy and Clinical Immunology of Monterrey, Mexico].
AB  - BACKGROUND: Atopic dermatitis is a chronic inflamatory disease of the skin which
      mainly affects children. It is characterized by itch and cutaneous hyperactivity
      with typical lesions that depend on the affected age group and the disease stage.
      It is frequently associated to rhinitis and asthma. OBJECTIVE: To identify the
      clinical characteristics of atopic dermatitis in patients treated at the Regional
      Center of Allergy and Clinical Immunology of Monterrey, NL, Mexico. MATERIAL AND
      METHODS: A retrospective and descriptive study was done by the review of clinical
      files of patients with atopic dermatitis diagnosis from January 1997 to May 2002.
      The statistical analysis was done by central tendency measures. RESULTS: We
      reviewed 119 clinical files, 53 (44.5%) were male and 66 (55.5%) female. The most
      frequent clinical manifestations were pruritus and eczematous lesions, both in
      117 patients (98.3%). Fifty-five percent of the patients initiated symptoms
      before 6 years of age. Eighty eight patients (74%) had family and/or personal
      history of atopia. Other associated manifestations were allergic rhinitis in 38
      patients (31.9%), asthma and rhinitis in 25 patients (21%) and only asthma in 2
      patients (1.7%). In 44 patients, food skin tests were done with a positive result
      in 25 patients, the most frequent was to egg (68%) and in 64 patients these were
      positive to aeroallergens being the most frequent Dermatophagoides p teronyssinus
      (85.1%). CONCLUSIONS: The pruritus and eczematous lesions were the most constant
      manifestations in this group of patients where family and/ or personal history of
      atopia was frequent.

PMID- 15237909
TI  - [Prevalence of allergic rhinitis in Durango, Mexico].
AB  - BACKGROUND: Allergic rhinitis has become the most frequent chronic disease of
      upper airways and its prevalence is increasing importantly in countries with
      systems of western life. OBJECTIVE: To determine the prevalence of allergic
      rhinitis and its subtypes in inhabitants of Durango, Mexico. MATERIAL AND
      METHODS: Through a descriptive, cross-sectional study, 1,320 inhabitants of
      Durango were studied. They were chosen randomly and accepted voluntarily to
      participate. A modification of the Middleton diary symptom questionnaire was used
      as a tool to determine the prevalence. RESULTS: The prevalence of allergic
      rhinitis in the general population was of 7.6% (95% CI 6.2-9.2). The prevalence
      of seasonal rhinitis was of 5.5% (95% CI 4.4-6.9), of perennial rhinitis, 2.1%
      (95% CI 1.4-3.0), for medical diagnosis, 4.3% (95% CI 3.4-5.8), and for survey,
      3.3% (95% CI 2.4-4.4). The highest frequency was found in persons of 5-9 years
      old (12.5%) and in women (5.1%). CONCLUSIONS: The prevalence of allergic rhinitis
      in Durango, Mexico, is similar to the national mean prevalence, but lower than
      that reported in developed countries.

PMID- 15237910
TI  - [HIV-infection and its implications on allergic diseases].
AB  - INTRODUCTION: In 1980 AIDS appeared in the USA in the homosexual community.
      CHARACTERISTICS OF THE VIRUS: A particle of HIV is formed by two identical RNA
      chains that are packed within a center of viral proteins, and surrounded by a
      double layer of fosfolipids derived from the cellular membrane of the host.
      CLINICAL SYMPTOMS: It starts with a severe infection, evolving in a progressive
      chronic infection reaching a final phase with a T CD4+ cellular count under 200
      cells per mm3, with incident infections, neoplasias, consumption syndrome, renal
      dysfunction, and degeneration of the central system. CONSEQUENCES IN ALLERGIC
      REACTION: Reactions to the use of drugs are the most frequent form of
      hypersensitivity caused by HIV compared to the general population. In this
      condition, a profile of TH2 cytocines are produced and they induce the synthesis
      of IgE against the drugs. IgE levels have been related to the progression of this
      condition. CONCLUSION: The increase of IgE is a risk factor to allergic reactions
      against these medications, as well as a severity index.

PMID- 15237911
TI  - [Hematopoietic steam cell transplantation in the management of systemic lupus
      erythematosus resistant to treatment].
AB  - Recently stem cell transplantation has been suggested like novel treatment in
      some severe auto-immune diseases, specifically in severe and refractory to
      conventional treatment in systemic lupus erythematosus patients. Autologus
      hematopoietic steam cell transplantation has been used in systemic lupus
      erythematosus, because it does not represent risk of development in graft versus
      host disease, which is the most common and severe complication in alogenic
      transplant. This type of transplant is poorly used because of the difficulty to
      get donors and laboratory background. Patients under this type of treatment
      received high dosage of chemotherapy, followed by alogenic hematopoietic steam
      cell transplantation with or without T cell depletion. Most of cases have
      successes in treatment and some patients get clinical and serological remission
      even for 34 months. However, a longer following is necessary to obtain concluding
      results. This paper reviews those treatments in clinical cases reported in the
      literature.

PMID- 15237913
TI  - [Occupational asthma].
AB  - Occupational bronchial asthma is a diagnostic, therapeutic and public health
      problem. The central clue for a proper diagnosis is to consider the problem when
      evaluating every patient with adult onset asthma. An objective confirmation is
      mandatory because clinical history often gives rise to many false positive cases.
      Avoidance of contact with the causative agent usually requires the change of work
      activity which results in an income decrease or unemployment. Despite many
      efforts in industrial hygiene, recent data shows asthma as the most prevalent
      cause in the Western world of occupational respiratory disease during working
      life. The challenge, from an occupational public health standpoint is to create
      the appropriate industrial hygiene conditions to reduce the burden of worker's
      exposure to allergens.

PMID- 15237914
TI  - [Exercise-induced bronchospasm. Diagnosis and management].
AB  - Exercise-induced bronchospam is a common entity in asthmatic children.
      Physiopathology involves airway cooling, airway dehydration and influx of
      inflammatory cells such as histamine or eicosanoids. Diagnosis is done by a
      suggestive clinical history, besides a VEF1 reversibility of 15% after the use of
      a beta agonist. Differential diagnosis should be done with similar presentation
      pathologies. Warming up routines and beta agonist should be used in regular bases
      as previous treatment in this kind of disease.

PMID- 15237912
TI  - [Reflections about allergic and crossed reactions to sulphonamides and drugs with
      radical-sulphonamide].
AB  - In the daily pharmacological therapy, some compounds may cause eventually
      allergic hypersensitivity reactions generating adverse effects. The objective of
      this study and its reflections has been to recommend caution, being prudent when
      expressing an opinion on risks and benefits of drugs themselves or some of their
      radicals that may contain because this attitude might produce a unsuitable
      concern. Drugs hypersensitivity (an unexpected pharmacological effect) may
      resemble a true allergic reaction but without the implication of IgE
      immunoglobulin. Such reactions are result of effector systems drug activation,
      leading to direct proallergic or proinflammatory chemical mediators release from
      mast cells, basophils and eosinophils. Sulphonamides are an illustrative example
      because they possess a chemical core resembling that from other kind of drugs 
      furosemide, some COXIB and others- besides its haptenic capability (even though
      they have different chemical structure). Selective COX 2 inhibitors are
      considered an accepted symptomatic therapy in rheumatic diseases as well as some
      other conditions where pain and inflammation are present; based on its
      generalized use in such conditions, authors decided to perform this investigation
      in the allergy clinics of Hospital General de Mexico and Hospital Espanol de
      Mexico, looking for cases of true allergic, crossed or hypersensitivity reactions
      related to one COXIB that includes a sulphamidic radical in its chemical
      structure. No clinical significance was found concerning the above mentioned
      reactions and the antiinflammatory-analgesic compound (celecoxib).

PMID- 15237915
TI  - Drastically downsized.

PMID- 15237916
TI  - Proteomics in pathology, research and practice.
AB  - Using more reliable and sophisticated protein biochemical techniques, it is
      possible to perform large scale, partly high-throughput characterization of the
      human proteome. Two-dimensional electrophoresis (2-DE) and mass spectrometry
      largely contribute to the identification of proteins and peptides. 2-DE has been
      used to study differential expression of peptides and proteins in various disease
      entities, searching for new diagnostic and therapeutic targets. However, 2-DE
      usually requires large amounts of starting material, is time-consuming, and
      reveals only a fraction of the proteins present in a given sample. More recently,
      the ProteinChip technology coupled with bioinformatics has gained considerable
      attention. This technique uses surface-enhanced laser desorption/ionization time
      of-flight mass spectrometry (SELDI TOF/MS) to screen any protein source for
      putative disease biomarkers in a spectrum from 2 to 20 kDa. Between 15,500 (low
      resolution SELDI TOF) and > 400,000 peptides and proteins (high-resolution SELDI
      TOF) can be resolved from a small sample volume (microl-range). Several studies
      have provided evidence that ProteinChip technology is capable of detecting early
      stage cancer by its unique cancer-specific proteomic finger prints, with
      sensitivities and specificities reaching far beyond well established serum-based
      tumor markers. In this review, we summarize the recent developments of proteomics
      in research and pathology, and critically discuss putative limitations and future
      applications of disease-specific biomarkers. Special emphasis is put on the
      former Human Protein Index project.

PMID- 15237917
TI  - Surface-enhanced laser desorption ionization time-of-flight mass spectrometry
      (SELDI TOF-MS) and ProteinChip technology in proteomics research.
AB  - In this review article, we describe some of the studies that have been performed
      using the surface-enhanced laser desorption ionization (SELDI) time-of-flight
      mass spectrometry and ProteinChip technology over the past few years, and
      highlight both their findings as well as limitations. Proteomic applications,
      such as target or marker identification and target validation or toxicology, will
      be addressed. We will also provide an examination of SELDI technology and go into
      the question of where possible future research may lead us.

PMID- 15237918
TI  - Array technology and proteomics in autoimmune diseases.
AB  - Two new technologies (tissue microarrays (TMAs) and proteomics) have generated a
      great amount of data in life science. High-density TMAs allow for the
      simultaneous analysis of proteins and RNA by various methods
      (immunohistochemistry, in situ hybridization, FISH) on a large scale and under
      highly standardized conditions. Proteomics includes a variety of techniques that
      are partly high throughput. These techniques aim at the innovation of proteins,
      the description of the domain structure, the determination of protein sequences
      and epitope characterization, and ultimately the definition of protein function
      and protein reactivities in immunologic processes. Proteins that have been
      characterized accordingly require validation mostly at the morphologic level of
      defined tissue, linking proteomics to TMAs. In autoimmune diseases, array-based
      antigenic fingerprinting of autoantibodies will drive the development and the
      selection of antigen-specific diagnostic tools and therapies. The powerful
      combination of genomics and proteomics formed in tissue arrays has the potential
      to change the way the biology of autoimmunity is studied. Novel targets of drug
      discovery, based on antigen-specific therapies to induce anergy, or regulatory T
      cells using the targeted autoantigens of individual patients could be developed
      in the coming decades.

PMID- 15237919
TI  - Proteomics in cancer cell research: an analysis of therapy resistance.
AB  - Proteomics, the global analysis of expressed cellular proteins, provides powerful
      tools for the detailed comparison of proteins from normal and neoplastic tissue.
      In particular, cancer cell culture models are suited for applying proteomics
      techniques, such as two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      and mass spectrometry, to identify specific protein expression profiles and/or
      proteins that may be associated with a defined phenotype of the cancer cells. As
      an instance of such an application of proteomics techniques, the detailed
      proteome analyses of different drug-resistant and thermoresistant cancer cell
      lines will be discussed. Finally, the potential roles of newly identified factors
      in a distinct biological mechanism have to be proven by functional studies. This
      experimental validation strategy will be discussed for two different factors
      identified by 2D-PAGE analyses of drug-resistant carcinoma cell lines, the
      "transporter associated with antigen presentation 1" (TAP1) and 14-3-3sigma.

PMID- 15237920
TI  - Expression and functional proteomics studies in colorectal cancer.
AB  - Cell dysfunction results from multiple rather than from single gene interactions
      in the majority of colorectal cancers (CRC). Proteins, not mRNA, are the
      functional molecules in the cell, and the relationship between gene expression
      measured at the mRNA level and the corresponding protein level is not linear.
      Current proteomics tools allow for the determination of post-translational
      modifications, and hence the presence of protein isoforms--some of them being
      disease-relevant. Thus, proteomics approaches are a welcome complement to
      traditional genetic approaches. In CRC, expression proteomics studies were
      carried out with colorectal cell lines, whole tissue biopsies, and purified
      epithelial cells. For CRC, two-dimensional electrophoresis reference maps,
      protein, and membrane protein databases are available on the internet. Functional
      proteomics studies have been performed to better understand signaling pathways,
      to characterize the molecular targets of novel drugs, and to identify tumor
      associated antigens in CRC. The increasing use of proteomics technologies, when
      addressing clinical problems, will accelerate the evolution towards personalized
      medicine in CRC.

PMID- 15237921
TI  - Proteomics and chronic inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are relatively frequent in developed countries.
      Physiopathological events involved in the etiology of IBDs include activation of
      immune, mesenchymal and epithelial cells. This review gives an overview of the
      currently applied proteomics technologies. It describes metabolic changes and
      goes into the approaches using this methodology to understand the molecular
      mechanisms implicated in the development of the disease.

PMID- 15237922
TI  - Proteomics in myocardial diseases.
AB  - Recently, proteome analysis has been introduced to analyze differential protein
      expression and cellular protein composition in cardiovascular medicine. Proteins
      expressed by diseased hearts (myocardial proteomics) were first investigated over
      a decade ago using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE).
      However, while 2D-PAGE is very successful for the abundant and moderately
      expressed proteins, it struggles to identify proteins expressed at low levels.
      However, the sensitivity of mass spectrometry has increased considerably during
      recent years, and technical progress widens the detection limits of mass
      spectrometric analysis. Proteomics now allows us to examine global alterations in
      protein expression in the diseased hearts, and will provide new insights into the
      cellular mechanisms involved in cardiac dysfunction. This review will summarize
      the present knowledge about the use of proteome analysis in myocardial diseases.

PMID- 15237923
TI  - Clinical proteomics in lung diseases.
AB  - Proteomics is a relatively new approach for understanding the pathology and
      pathogenesis of various diseases. It has also been used for characterizing the
      modifications in protein expression during the development of interstitial lung
      diseases, in lung tumors, or following exposure to exogenous stress signals. We
      compared the protein composition of primary human lung fibroblasts derived from
      patients with lung fibrosis and control fibroblasts of unaffected lung tissues.
      We found a predominant modulation in proteins related to the cytoskeleton,
      including decreased expression of vimentin and lamin A/C, and increased
      expression of moesin. Furthermore, we observed lower levels of components of the
      antioxidative system, such as omega class glutathione S-transferase and an up
      regulation of an intracellular chloride channel. In fibroblasts obtained from
      fibrotic lungs, the expression of a major histocompatibility complex class I C
      was decreased, and so was the expression of tripeptidyl-peptidase-I-precursor, a
      collagen-degrading exopeptidase. Our results and the studies reviewed in this
      paper represent just the beginning of detailed studies that should unravel the
      relevance and the functional consequences of differential protein expressions in
      the diseased lung.

PMID- 15237924
TI  - Epithelial cell preparation for proteomic and transcriptomic analysis in human
      pancreatic tissue.
AB  - Standardized sample preparation procedures constitute a prerequisite for
      obtaining reliable and reproducible results in gene expression research in
      humans. In particular, in diseases such as pancreatic cancer and pancreatitis,
      isolating epithelial cells is an important step preceding such research. In
      pancreatic tissue, the high amount of RNAases is a further problem when it comes
      to obtaining high-quality RNA, and the presence of secreted proteases accelerates
      protein degradation. We developed a successful method that addresses these
      different problems. This method, which uses epithelial cell surface antibody Ber
      Ep4, proteases, and RNAases inhibitors, leads to a significant enrichment (> 95%
      purity) of epithelial cells from fresh human tissue samples and allows for both
      proteomics (Western Blot, 2D PAGE) and transcriptomics studies (rtPCR, cDNA
      microarray). Compared with other cell purification procedures, this method is
      characterized by several advantages: a large quantity of cells available for
      downstream analysis, combined transcriptomics and proteomics studies using the
      same samples, better reproducibility of proteomics studies, and an acceptable
      yield (63%) for gene expression arrays studies. Moreover, a quality control
      protocol addressing the needs of the industry and the requirements of regulatory
      agencies is proposed.

PMID- 15237925
TI  - Proteome analysis reveals disease-associated marker proteins to differentiate RA
      patients from other inflammatory joint diseases with the potential to monitor
      anti-TNFalpha therapy.
AB  - New experimental approaches of molecular medicine such as transcriptome and
      proteome analysis have been implemented in rheumatology research. Two-dimensional
      gel electrophoresis in combination with mass spectrometry was used to visualize
      and to identify proteins in synovial fluid (SF) and plasma samples from patients
      with rheumatoid arthritis (RA) and osteoarthritis (OA). The small calcium binding
      protein S100A9 (MRP14) was identified as a discriminatory marker protein in SF by
      global proteomic analysis. To confirm these results and to examine the
      reproducibility and the applicability as a diagnostic marker, levels of the
      S100A8 (MRP8)/A9 (MRP14) heterocomplex in plasma and in synovial fluid were
      validated from patients with RA, OA, and other inflammatory joint diseases using
      enzyme immunoassay techniques. It was found that plasma levels of the S100A8/A9
      heterocomplex correlate well with levels in SF, and hence, determination of
      plasma levels can be used to distinguish RA patients from patients with other
      inflammatory joint diseases, as well as from OA patients and controls. Initial
      studies on RA patients also indicate that plasma levels of the S100A8/A9
      heterocomplex are a useful marker in monitoring anti TNFalpha therapy.

PMID- 15237926
TI  - Bioinformatics in proteomics: application, terminology, and pitfalls.
AB  - Bioinformatics applies data mining, i.e., modern computer-based statistics, to
      biomedical data. It leverages on machine learning approaches, such as artificial
      neural networks, decision trees and clustering algorithms, and is ideally suited
      for handling huge data amounts. In this article, we review the analysis of mass
      spectrometry data in proteomics, starting with common pre-processing steps and
      using single decision trees and decision tree ensembles for classification.
      Special emphasis is put on the pitfall of overfitting, i.e., of generating too
      complex single decision trees. Finally, we discuss the pros and cons of the two
      different decision tree usages.

PMID- 15237927
TI  - Proteomics in pathology, research and practice: ethical considerations.
AB  - A researcher should always seek advice from his responsible ethics committee.
      Usually, advisory discussions with physicians doing research are not problematic
      in ethical terms when they want to examine biological material obtained,
      especially, when the material is no longer needed, the material will be used
      anonymized, no individualizing genes will be examined, the aims of research are
      not disputed in ethical terms, research is not expected to yield results of
      individual relevance to the person affected, there is no indication that the
      person affected will object to research and the expenditure for obtaining the
      individual consent is excessively high.

PMID- 15237928
TI  - Basal and glucose-suppressed GH levels less than 1 microg/L in newly diagnosed
      acromegaly.
AB  - The development of highly sensitive and specific GH assays has necessitated a
      critical re-evaluation of the biochemical criteria needed for the diagnosis of
      acromegaly. Use of these assays has revealed that GH levels after oral glucose in
      healthy subjects and postoperative patients with active acromegaly can be
      significantly less than previously recognized with older GH assays. In order to
      assess GH criteria for newly diagnosed acromegaly with a modern assay we have
      evaluated GH levels in 25 patients referred to our Neuroendocrine Unit for
      evaluation of untreated acromegaly. All patients underwent measurement of basal
      GH and IGF-I levels and 15 of these patients also underwent oral glucose
      tolerance testing for GH suppression (OGTT). Basal GH levels were < 1.0 microg/L
      at diagnosis in 5 of these 25 patients. Nadir GH levels were less than 1 microg/L
      also in 5 of 15 patients, and as low as 0.42 microg/L. All patients had elevated
      IGF-I levels preoperatively and pathological confirmation of a GH secreting
      pituitary tumor at the time of transsphenoidal surgery. The clinical
      presentations of these patients was variable. Most patients presented with
      classical manifestations of acromegaly, but 3 of the 5 patients with low nadir GH
      values had only very subtle signs of acromegaly. Although most newly diagnosed
      patients have classically elevated GH levels and obvious clinical features of
      acromegaly, early recognition of disease may uncover patients with milder
      biochemical and clinical abnormalities. The diagnosis should not be discounted in
      patients who have elevated IGF-I levels, but have basal or nadir GH levels less
      than 1 microg/L. Conventional GH criteria for the diagnosis of acromegaly cannot
      be applied to the use of modern sensitive and specific GH assays.

PMID- 15237929
TI  - Sheehan's syndrome.
AB  - Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to
      severe postpartum hemorrhage. It may be rarely seen without massive bleeding or
      after normal delivery. Improvement in obstetric care and availability of rapid
      blood transfusion coincided with a remarkable reduction in the frequency of
      Sheehan's syndrome particularly in western society. But it has recently been
      reported more often from well-developed countries. It is one of the most common
      causes of hypopituitarism in underdeveloped or developing countries. Enlargement
      of pituitary gland, small sella size, disseminated intravascular coagulation and
      autoimmunity have been suggested to play a role in the pathogenesis of Sheehan's
      syndrome in women who suffer from severe postpartum hemorrhage. The patients may
      seek medical advice because of various presentations ranging from non-specific
      symptoms to coma and the clinical manifestation may change from one patient to
      another. Failure of postpartum lactation and failure to resume menses after
      delivery are the most common presenting symptoms. Although a small percentage of
      patients with Sheehan's syndrome may cause abrupt onset severe hypopituitarism
      immediately after delivery, most patients have a mild disease and go undiagnosed
      and untreated for a long time. It may result in partial or panhypopituitarism and
      GH is one of the hormones lost earliest. The great majority of the patients has
      empty sella on CT or MRI. Lymphocytic hypophysitis should be kept in mind in
      differential diagnosis. In this review, the old and recent data regarding
      Sheehan's syndrome are presented.

PMID- 15237931
TI  - Acromegalic cardiomyopathy: a review of the literature.
AB  - Acromegaly is characterized by a high prevalence of cardiovascular complications
      that account for increased morbidity and mortality. Several studies emphasized
      the role of GH and IGF-1 excess in cardiac dysfunction. Coexisting factors such
      as hypertension, glucose tolerance abnormalities and coronary artery disease have
      a potential role in the progression of the acromegalic cardiomyopathy. Herein, we
      review the most relevant pathophysiological, functional and morphological
      findings in this specific disease.

PMID- 15237930
TI  - Proteomics and transcriptomics analyses of secretagogin down-regulation in human
      non-functional pituitary adenomas.
AB  - In order to explore the presence of, and the potential role of, secretagogin in
      human pituitary adenomas, an analytical strategy that integrated comparative
      proteomics and comparative transcriptomics was used to detect the protein and the
      mRNA expression, respectively, of secretagogin in human non-functional pituitary
      adenomas compared to controls. Proteomics methods included two-dimensional gel
      electrophoresis, 2D gel image analysis, mass spectrometry [matrix-assisted laser
      desorption/ionization-time of flight-peptide mass fingerprinting (MALDI-TOF PMF)
      and liquid chromatography-electrospray ionization-quadrupole-ion trap tandem mass
      spectrometry (LC-ESI-Q-IT MS/MS)], and database analysis. Transcriptomics methods
      included the GeneChip microarray, image processing, and data analysis. The
      proteomics and transcriptomics data demonstrated that secretagogin was
      significantly down-regulated at the protein and mRNA levels, respectively, in the
      human non-functional (NF) pituitary adenomas (NF-, LH+, FSH+, and FSH+ + LH+).
      For the secretagogin protein, the expression level was NF- < FSH+ + LH+ < FSH+ <
      LH+ < Control, with a range of down-regulation of 2.2-6.9 fold in non-functional
      pituitary adenomas compared to controls, with a significant difference (p <
      0.001). For secretagogin mRNA, the expression level was NF- < LH+ < FSH+ + LH+ <
      FSH+ < Control, with a range of down-regulation of 1.8-18.6 fold in non
      functional pituitary adenomas compared to controls that was significant (p <
      0.05). The secretagogin protein expression correlated significantly with its mRNA
      expression. Those results suggest that secretagogin might play a role in human
      non-functional pituitary adenomas. This novel finding may provide clues to
      clarify the basic molecular mechanisms of pituitary adenoma formation, and to
      identify new tumor-related markers.

PMID- 15237932
TI  - Sustained improvement in vision in a recurrent growth hormone secreting
      macroadenoma during treatment with octreotide in the absence of marked tumour
      shrinkage.
AB  - Visual improvement following octreotide for growth hormone secreting pituitary
      macroadenomas is uncommon without tumour shrinkage. A 45-year old lady presented
      with blurred vision for 12 months. Visual assessment revealed a bitemporal
      hemianopia and CT scan demonstrated a large pituitary tumour with lateral and
      suprasellar extension. Acromegaly was confirmed by 75 g glucose tolerance
      testing. Primary transsphenoidal surgery was performed with normalisation of
      visual acuity and fields of vision. Post-operatively she had anterior pituitary
      hormone deficiency. As GH and IGF-1 levels remained elevated she underwent
      external pituitary irradiation. CT scanning demonstrated tumour shrinkage
      associated with a modest fall in GH levels. IGF-1 levels remained elevated
      falling to the age-related upper limit of normal after 5 years. At regular review
      she had stable visual acuity and fields of vision. She presented as an emergency
      7 years from presentation with reduced vision and recurrence of bitemporal
      hemianopia. An MRI demonstrated a large pituitary adenoma. We therefore undertook
      a carefully monitored trial of octreotide with great caution with daily
      reassessment of acuity and fields. A decision was made to proceed to surgery in
      the event of deterioration or lack of improvement after a short trial over 5-7
      days. We observed normalisation of visual acuity and perimetry within 3 days. She
      then commenced long-acting octreotide (Sandostatin LAR) 20 mg every 28 days. MRI
      after 1 week showed shrinkage of the tumour by a few millimetres. Five months
      later repeat MRI failed to show any further improvement in tumour size. However
      she remains well 29 months from treatment with normal vision and is being
      monitored carefully as her chosen form of therapy. Somatostatin analogues may be
      effective as therapy in a selected group of patients with acromegaly and visual
      loss who are not suitable for pituitary surgery. If used in this way the drug
      must be given cautiously with frequent detailed ongoing visual assessments. In
      this present case there has been a restoration of vision but the long-term
      outlook remains guarded without significant tumor shrinkage.

PMID- 15237933
TI  - Serial MR intensity changes of the posterior pituitary in patients with diabetes
      insipidus after transsphenoidal surgery for pituitary adenomas: report of two
      cases.
AB  - This is the first report describing magnetic resonance (MR) intensity changes of
      the posterior pituitary gland in the patients suffering from the classical
      "triphasic" diabetes insipidus (DI) after transsphenoidal surgery for pituitary
      adenomas. A 21-year-old female and a 54-year-old female were admitted to our
      hospital with the diagnosis of Cushing's disease and acromegaly due to pituitary
      microadenomas, respectively. No evidence of DI was found, and T1-weighted MR
      images exhibited "bright spot" corresponding to the posterior pituitary in both
      cases. Both experienced the classical "triphasic" pattern of water metabolism
      disturbance after successful transsphenoidal resection of pituitary adenomas,
      that is, polyuria-oliguria-polyuria. The MR signal hyperintensity in posterior
      pituitary was detected during the first polyuric phase, but the hyperintensity
      disappeared during the second polyuric phase. In addition, "bright spot" was
      restored along with the recovery from DI in the chronic phase. These findings of
      serial MR images supported that the first DI phase of the classical triphasic
      course of water metabolism disturbance was caused by secretional dysfunction of
      stored vasopressin from the posterior gland, whereas the second DI phase was due
      to impairment in the functional integrity producing vasopressin-containing
      granules after depletion of vasopressin in the oliguric phase.

PMID- 15237934
TI  - Coexistence of a pituitary macroadenoma and pheochromocytoma--a case report and
      review of the literature.
AB  - A 59-year old man, who had a hypertensive crisis during transsphenoidal surgery
      for a pituitary macroadenoma, was subsequently found to have an adrenal
      pheochromocytoma. A total of twenty-five cases describing the coexistence of a
      pituitary adenoma and pheochromocytoma have been reported in the literature over
      the past 40 years. Among pituitary tumors, acromegaly has been the most common.
      In an effort to identify the relationship between the two tumors, multiple
      theories have been suggested including fortuitous association, overlap or
      variants of MEN syndromes, and ectopic production of a trophic hormone by the
      pheochromocytoma. The high risk of mortality and morbidity associated with
      undiagnosed pheochromocytoma warrants careful attention to the possibility of
      such a coexistence.

PMID- 15237935
TI  - Enzyme-linked immunosorbent assay-based detection of free trenbolone in bovine
      bile.
AB  - A rapid antibody-based detection system has been developed for the presence of
      free trenbolone in bovine samples. Polyclonal antibodies were produced that
      showed specificity toward epitopes located around the steroidal A-ring of the
      trenbolone molecule. These antibodies were shown to have little or no recognition
      for many closely related compounds. The antibodies were utilized as the specific
      biorecognition molecules in competitive and inhibitive enzyme-linked
      immunosorbent assay systems. While both assays were able to detect low nanogram
      concentrations of trenbolone in bovine bile, the competitive format was more
      sensitive (2.41 vs 17.15 ng/mL for TRAb2 and 3.31 vs 30.73 ng/mL for TRAb1). This
      format was also more accurate and the data produced by this assay fitted more
      closely to the four parameter equation used to calculate the standard curve. This
      was a common finding with both of the polyclonal antibodies, suggesting that this
      was a characteristic of the format used.

PMID- 15237936
TI  - Nanocolloidal gold-based immunoassay for the detection of the N-methylcarbamate
      pesticide carbofuran.
AB  - Nanocolloidal gold particles were prepared and labeled to an anti-carbofuran
      monoclonal antibody (Mab). This conjugate was dispensed on the conjugated pad of
      a porous glass fiber. Ovalbumin (OVA)-carbofuran and goat anti-mouse IgG were
      dispensed on the nitrocellulose (NC) membrane and served as the test line and
      control line, respectively. The carbofuran-containing sample migrated to the NC
      membrane and reacted with the anti-carbofuran Mab labeled with the colloidal
      gold. The mixture diffused along the membrane and passed through the OVA
      carbofuran in the test line via capillary action. The more analyte present in the
      sample, the more effectively it will compete with the carbofuran immobilized on
      the test line for binding to the limited amount of antibody labeled with
      colloidal gold. An adequate amount of carbofuran could prevent attachment of the
      colored conjugate to the test line. The presence or absence of a colored band on
      the test line could indicate a negative or positive result, respectively. When
      measured to the water sample spiked with carbofuran, this was obtained at or
      above 0.25 mg/L of carbofuran. The major advantages of the one-step strip test
      are that the detection time needed was <10 min and all of the reagents are
      included in the test device.

PMID- 15237937
TI  - Polyphenol screening of pomace from red and white grape varieties (Vitis vinifera
      L.) by HPLC-DAD-MS/MS.
AB  - Phenolic compounds of 14 pomace samples originating from red and white winemaking
      were characterized by HPLC-MS. Up to 13 anthocyanins, 11 hydroxybenzoic and
      hydroxycinnamic acids, and 13 catechins and flavonols as well as 2 stilbenes were
      identified and quantified in the skins and seeds by HPLC-DAD. Large variabilities
      comprising all individual phenolic compounds were observed, depending on cultivar
      and vintage. Grape skins proved to be rich sources of anthocyanins,
      hydroxycinnamic acids, flavanols, and flavonol glycosides, whereas flavanols were
      mainly present in the seeds. However, besides the lack of anthocyanins in white
      grape pomace, no principal differences between red and white grape varieties were
      observed. This is the first study presenting comprehensive data on the contents
      of individual phenolic compounds comprising all polyphenolic subclasses of grapes
      including a comparison of several red and white pomaces from nine cultivars. The
      results obtained in the present study confirm that both skins and seeds of most
      grape cultivars constitute a promising source of polyphenolics.

PMID- 15237938
TI  - Synthesis of haptens and development of an immunoassay for the olive fruit fly
      pheromone.
AB  - An enzyme-linked immunosorbent assay (ELISA) for the olive fruit fly pheromone,
      Bactrocera oleae Gmelin, was developed. The assay uses polyclonal antibodies,
      raised in rabbits, against (+/-)-beta-[3-(1,7-dioxaspiro[5.5]undecane)]propionic
      acid, 2 (hapten I), conjugated to the KLH (keyhole limpet hemocyanin) by the
      carbodiimide method. A second hapten, (+/-)-delta-[3-(1,7
      dioxaspiro[5.5]undecane)]butylamine, 3 (hapten II), after conjugation to a biotin
      moiety, was used for indirect immobilization onto ELISA microwells precoated with
      the glycoprotein avidin. The developed ELISA method measures the synthetic olive
      fruit fly pheromone in concentrations ranging between 0.08 and 10 microg/mL and
      shows great promise for practical applications for pheromone detection in
      environmental and biological samples. The results obtained strongly indicate that
      this technique, to our knowledge the first insect pheromone enzyme-linked
      immunosorbent assay so far reported, is a fast, sensitive, inexpensive, and
      highly convenient method for the analysis of a volatile and low molecular weight
      compound such as 1,7-dioxaspiro[5.5]undecane, 1.

PMID- 15237939
TI  - Determination of sucralose in Splenda and a sugar-free beverage using high
      performance anion-exchange chromatography with pulsed amperometric detection.
AB  - Sucralose is a chlorinated carbohydrate nonnutritive sweetener of food and
      beverage products. The determination of sucralose in food and beverages is
      important to ensure consistency in product quality. Sucralose was determined in
      two commercial products without sample preparation using high-performance anion
      exchange (HPAE) chromatography coupled with pulsed amperometric detection (PAD).
      Sucralose was determined with a 10 min isocratic separation. To determine
      sucralose and other carbohydrates (e.g., dextrose) simultaneously, a gradient
      separation was developed. The linear range of electrochemical response extended
      over 3 orders of magnitude, from 0.01 (LOD) to 40 microM (16 microg/mL; 25 microL
      injection). High precision, high spike recovery, and method ruggedness were
      observed for both samples.

PMID- 15237940
TI  - Antioxidative and antimutagenic activities of 4-vinyl-2,6-dimethoxyphenol
      (canolol) isolated from canola oil.
AB  - A potent antioxidative compound in crude canola oil, canolol, was recently
      identified, and reported herein are studies of its scavenging capacity against
      the endogenous mutagen peroxynitrite (ONOO(-)). ONOO(-) is generated by the
      reaction between superoxide anion radical and nitric oxide, both of which are
      produced by inflammatory leukocytes. Among various antioxidative substances of
      natural or synthetic origin, canolol was one of the most potent antimutagenic
      compounds when Salmonella typhimurium TA102 was used in the modified Ames test.
      Its potency was higher than that of flavonoids (e.g., rutin) and alpha-tocopherol
      and was equivalent to that of ebselen. Canolol suppressed ONOO(-)-induced
      bactericidal action. It also reduced intracellular oxidative stress and apoptosis
      in human cancer SW480 cells when used at a concentration below 20 microM under
      H(2)O(2)-induced oxidative stress. In addition, canolol suppressed plasmid DNA
      (pUC19) strand breakage induced by ONOO(-), as revealed by agarose gel
      electrophoresis.

PMID- 15237941
TI  - Properties of 3-deoxyanthocyanins from sorghum.
AB  - There is increasing interest in natural food colorants with functional
      properties. Anthocyanins from black, brown (containing tannins), and red sorghums
      were characterized by spectrophotometric and HPLC techniques. The antioxidant
      activity and pH stability of the anthocyanins were also determined. Sorghum brans
      had 3-4 times higher anthocyanin contents than the whole grains. Black sorghum
      had the highest anthocyanin content (average = 10.1 mg/g in bran). The brown and
      red sorghum brans had anthocyanin contents of 2.8-4.3 mg/g. Only 3
      deoxyanthocyanidins were detected in sorghum. These compounds are more stable to
      pH-induced color change than the common anthocyanidins and their glycosides.
      Additionally, crude sorghum anthocyanin extracts were more stable than the pure 3
      deoxyanthocyanidins. The antioxidant properties of the 3-deoxyanthocyanidins were
      similar to those of the anthocyanins. Pigmented sorghum bran has high levels of
      unique 3-deoxyanthocyanidins, which are stable to change in pH and have a good
      potential as natural food pigments.

PMID- 15237942
TI  - Chemical composition and mosquito larvicidal activity of essential oils from
      leaves of different Cinnamomum osmophloeum provenances.
AB  - Chemical compositions of leaf essential oils from eight provenances of indigenous
      cinnamon (Cinnamomum osmophloeum Kaneh.) were compared. According to GC-MS and
      cluster analyses, the leaf essential oils of the eight provenances and their
      relative contents were classified into five chemotypes-cinnamaldehyde type,
      linalool type, camphor type, cinnamaldehyde/cinnamyl acetate type, and mixed
      type. The larvicidal activities of leaf essential oils and their constituents
      from the five chemotypes of indigenous cinnamon trees were evaluated by mosquito
      larvicidal assay. Results of larvicidal tests demonstrated that the leaf
      essential oils of cinnamaldehyde type and cinnamaldehyde/cinnamyl acetate type
      had an excellent inhibitory effect against the fourth-instar larvae of Aedes
      aegypti. The LC(50) values for cinnamaldehyde type and cinnamaldehyde/cinnamyl
      acetate type against A. aegypti larvae in 24 h were 36 ppm (LC(90) = 79 ppm) and
      44 ppm (LC(90) = 85 ppm), respectively. Results of the 24-h mosquito larvicidal
      assays also showed that the effective constituents in leaf essential oils were
      cinnamaldehyde, eugenol, anethole, and cinnamyl acetate and that the LC(50)
      values of these constituents against A. aegypti larvae were <50 ppm.
      Cinnamaldehyde had the best mosquito larvicidal activity, with an LC(50) of 29
      ppm (LC(90) = 48 ppm) against A. aegypti. Comparisons of mosquito larvicidal
      activity of cinnamaldehyde congeners revealed that cinnamaldehyde exhibited the
      strongest mosquito larvicidal activity.

PMID- 15237943
TI  - Insecticidal effect of phthalides and furanocoumarins from Angelica acutiloba
      against Drosophila melanogaster.
AB  - Insecticidal activity of Angelica acutiloba extract and its constituents was
      investigated and compared with that of rotenone. Bioassay-guided isolation of the
      chloroform extract of A. acutiloba against larvae of Drosophila melanogaster
      afforded two phthalides, (Z)-butylidenephthalide (1) and (Z)-ligustilide (2), and
      two furanocoumarins, xanthotoxin (3) and isopimpinellin (4). The structures of
      these compounds were established by spectroscopic analysis. The isolated
      compounds 1, 2, 3, and 4 exhibited LC(50) values of 0.94, 2.54, 3.35, and 0.82
      micromol/mL of diet concentration against larvae of D. melanogaster,
      respectively. Against both sexes (males/females, 1:1) of adults (5-7 days old),
      compound 1 showed the most potent activity with a LD(50) value of 0.84
      microg/adult. Compound 1 is a more active insecticide than rotenone (LD(50) =
      3.68 microg/adult) and has potential as a novel insect control agent. However,
      compound 2 was inactive against adults. The structure-activity relationship of
      phthalides isolated indicated that the aromaticity appeared to play an important
      role in the activity of both larvae and adults. To determine the insecticide mode
      of action for acute adulticidal activity, acetylcholinesterase (AChE) inhibitory
      activity was also investigated in vitro, and the result indicated that the acute
      adulticidal activity of compounds 3 and 4 was due to the inhibition of AChE.

PMID- 15237944
TI  - Benzothiadiazole enhances resveratrol and anthocyanin biosynthesis in grapevine,
      meanwhile improving resistance to Botrytis cinerea.
AB  - Pre-harvest multiple treatments of grapevine (cv. Merlot) with the plant
      activator benzothiadiazole (BTH, 0.3 mM) enhanced trans-resveratrol content in
      berries by about 40%. An even more striking effect was observed on anthocyanin
      synthesis, particularly on malvidine 3-glucoside, malvidine 3-(6-O
      acetyl)glucoside and malvidine 3-(6-O-p-coumaroyl)glucoside, whose amounts were
      more than doubled. These data were obtained with a novel and time-saving HPLC
      method, set up for the simultaneous detection of stilbenes and anthocyanins,
      using an RF-10Axl fluorimetric detector instrument, with excitation at 330 nm and
      emission at 374 nm, and a SPD-Avp UV detector with absorption at 520 nm.
      Furthermore, BTH treatments induced systemic acquired resistance in grapevine, as
      assessed by inoculating clusters from treated and untreated plants with Botrytis
      cinerea. Disease severity, estimated according to the percentage of infected
      berries per cluster, was significantly reduced in grapes from BTH-treated plants.
      These results indicate that BTH treatments, besides improving the content of two
      important classes of nutraceuticals, with their well-known antioxidant,
      antitumoral, and phytoestrogenic activities, could be exploited in vineyard to
      protect grape against gray mould infection, thereby limiting an excessive use of
      fungicides

PMID- 15237945
TI  - Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the
      flavonol quercetin, in human platelets.
AB  - The aim of this study was to systematically examine the inhibitory mechanisms of
      rutin, a well-known flavonoid in platelet aggregation. In this study, rutin
      concentration-dependently (250 and 290 microM) inhibited platelet aggregation in
      human platelets stimulated by agonists (i.e., collagen). Rutin (250 and 290
      microM) did not significantly interfere with the binding of FITC-triflavin to the
      glycoprotein IIb/IIIa complex in human platelets. Rutin (250 and 290 microM)
      markedly inhibited intracellular Ca(2+) mobilization and thromboxane A(2)
      formation in human platelets stimulated by collagen. Rapid phosphorylation of a
      platelet protein of M(r) 47000 (P47), a marker of protein kinase C activation,
      was triggered by collagen (1 microg/mL). This phosphorylation was markedly
      inhibited by rutin (250 and 290 microM). On the other hand, rutin (250 and 290
      microM) did not significantly increase the formations of cyclic AMP and nitric
      oxide/cyclic GMP in platelets. In conclusion, these results indicate that the
      antiplatelet activity of rutin may involve the following pathways: rutin
      inhibited the activation of phospholipase C, followed by inhibition of protein
      kinase C activity and thromboxane A(2) formation, thereby leading to inhibition
      of the phosphorylation of P47 and intracellular Ca(2+) mobilization, finally
      resulting in inhibition of platelet aggregation.

PMID- 15237946
TI  - PCR-ELISA for the semiquantitative detection of Nile perch (Lates niloticus) in
      sterilized fish muscle mixtures.
AB  - A PCR-ELISA technique was developed for the semiquantitative detection of Nile
      perch (Lates niloticus) in experimentally sterilized fish muscle mixtures.
      Specific oligonucleotides derived from the 5S rDNA gene of Nile perch were
      selected. A forward primer, together with a reverse digoxigenin-labeled primer,
      permitted the amplification of specific 185 bp DNA fragments showing DNA
      intensities proportional to the contents of Nile perch muscle tissue in the fish
      mixtures. A biotinylated probe immobilized onto streptavidin-coated microplates
      was used to capture the digoxigenin-labeled fragments that were detected with
      peroxidase antidigoxigenin conjugate. Subsequent enzymatic conversion of
      substrate gave distinct absorbance differences when assaying fish binary mixtures
      containing different percentages of Nile perch muscle.

PMID- 15237947
TI  - Effects of degree of enzymatic interesterification on the physical properties of
      margarine fats: solid fat content, crystallization behavior, crystal morphology,
      and crystal network.
AB  - In this study enzymatic-interesterified margarine fats with different conversion
      degrees were produced in a packed-bed reactor. The effects of conversion degree
      on the formation of free fatty acids and diacyglycerols, solid fat content,
      crystallization behavior, microstructure, and crystal network were investigated,
      and the enzymatically interesterified products were compared with a chemically
      interesterified product. Formation of free fatty acids and diacyglycerols
      increased slightly with increasing conversion degree. The solid fat content was
      higher at 10 and 20 degrees C and lower at 30, 35, and 40 degrees C with
      increasing conversion degree. Increased conversion degree from the blend to
      products, measured by X-ray with addition of 50% of rapeseed oil for dilution,
      caused the content of beta to decrease from 100% to 33%, and 30% and eventually
      to pure beta' crystal. However, double chain packing was observed for both the
      blend and products. Isothermal crystallization kinetics was characterized by the
      Fisher-Turnbull model. The highest free energy was observed for the blend. A
      small deformation with oscillation tests shows a significant difference between
      the blend and interesterified products. The differences of microstructure between
      the blend, different conversion degree, and chemical randomized product were
      observed.

PMID- 15237948
TI  - Fumonisin in tortillas produced in small-scale facilities and effect of
      traditional masa production methods on this mycotoxin.
AB  - Four small tortilla plants were visited in Cameron County, Texas, where
      observations were made on their production methods. Samples of liquids and solids
      were collected at each stage of the nixtamalization process, and the pH was
      recorded. Samples were analyzed for fumonisin B(1) (FB(1)) using an
      immunoaffinity column/HPLC method chosen for its sensitivity for FB(1). It was
      found that production methods were highly variable among the producers visited,
      with major differences particularly in the amount of lime added and boiling
      times. As reported by others working in Mexico and Central America, FB(1) was
      found in some tortillas. This led to studies of the effects of the various
      recipes and across a greater range of initial FB(1) concentration/damaged corn
      than has typically been reported. Five initial concentrations of FB(1) were
      tested using irradiated corn kernels inoculated with Fusarium verticillioides MRC
      826 as the source of FB(1). The amount of FB(1) detected in the masa and
      tortillas decreased as the concentration of Ca(OH)(2) increased, and boiling time
      had no apparent effect. Unexpectedly, as the initial concentrations were
      increased in the corn prior to nixtamalization, greater percentage reductions in
      FB(1) were observed.

PMID- 15237949
TI  - Formation and evolution of monoepoxy fatty acids in thermoxidized olive and
      sunflower oils and quantitation in used frying oils from restaurants and fried
      food outlets.
AB  - The formation and evolution of monoepoxy fatty acids, arising from oleic and
      linoleic acids, were investigated in olive oil and conventional sunflower oil,
      representatives of monounsaturated and polyunsaturated oils, respectively, during
      thermoxidation at 180 degrees C for 5, 10, and 15 h. Six monoepoxy fatty acids,
      cis-9,10- and trans-9,10-epoxystearate, arising from oleic acid, and cis-9,10-,
      trans-9,10-, cis-12,13-, and trans-12,13-epoxyoleate, arising from linoleic acid,
      were analyzed by gas chromatography after oil derivatization to fatty acid methyl
      esters. Considerable amounts, ranging from 4.29 to 14.24 mg/g of oil in olive oil
      and from 5.10 to 9.44 mg/g of oil in sunflower oil, were found after the heating
      periods assayed. Results showed that the monoepoxides quantitated constituted a
      major group among the oxidized fatty acid monomers formed at high temperature.
      For similar levels of degradation, higher contents of the monoepoxides were found
      in olive oil than in sunflower oil. Ten used frying oils from restaurants and
      fried-food outlets in Spain were analyzed to determine the contents of the
      monoepoxides in real frying oil samples. Levels ranged from 3.37 to 14.42 mg/g of
      oil. Results show that, for similar degradation levels, the monoepoxides were
      more abundant in the monounsaturated oils than in the polyunsaturated oils.

PMID- 15237950
TI  - Hemoglobin-mediated oxidation of washed minced cod muscle phospholipids: effect
      of pH and hemoglobin source.
AB  - Lipid pro-oxidative properties and deoxygenation/autoxidation patterns of
      hemoglobins from nonmigratory white-fleshed fish (winter flounder and Atlantic
      pollock) and migratory dark-fleshed fish (Atlantic mackerel and menhaden) were
      compared during ice storage at pH 7.2 and 6. A washed cod mince model system and
      a buffer model system were used for studying lipid changes and hemoglobin
      changes, respectively. TBARS and painty odor were followed as markers for lipid
      oxidation. At pH 6, all four hemoglobins were highly and equally active as pro
      oxidants. At pH 7.2, pro-oxidation by all hemoglobins except that from pollock
      was slowed down, and activity ranked as pollock > mackerel > menhaden > flounder.
      The higher catalytic activities of the hemoglobins at pH 6 than at pH 7.2
      corresponded with higher formation of deoxyhemoglobin and methemoglobin. Pollock
      had the most extensive formation of deoxy- and methemoglobin at both pH values,
      which could explain its high catalytic activity. The pro-oxidative differences
      among the other hemoglobins at pH 7.2 did not correlate with deoxygenation and
      autoxidation reactions. This indicates involvement of other structural
      differences between the hemoglobins such as differences in the heme-crevice
      volume. It is suggested that a biological reason for the species differences was
      their adaptations to different depths/water temperatures.

PMID- 15237951
TI  - Levels of benzo[a]pyrene (BaP) in "mozzarella di bufala campana" cheese smoked
      according to different procedures.
AB  - The content of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, was
      determined by HPLC-FL in "mozzarella di bufala campana" cheese, a stretched
      cooked cheese, either experimentally smoked according to traditional procedures,
      using straw, cardboard, and wood shavings or aromatized with smoke flavoring. The
      BaP residues, researched also in cheese samples sold at retail, were detected in
      the rind, in the core, and in the slice (outer and inner parts). In the cheeses
      experimentally smoked with straw and cardboard the BaP levels, ranging from 0.38
      to 2.12 microg kg(-1) and from 0.46 to 2.40 microg kg(-1), respectively, were
      statistically higher than those of the cheeses smoked with wood shavings and
      aromatized with liquid smoke (from 0.19 to 0.80 microg kg(-1) and from 0.18 to
      0.50 microg kg(-1), respectively). However the cheeses treated with liquid smoke
      flavor showed a BaP content exceeding the level allowed by the European Union. In
      the samples sold at retail, smoked with straw, values were lower than those
      obtained from samples smoked experimentally with the same combustible. This is
      probably due to different smoking technologies among the several provinces of the
      Protected Designation of Origin (PDO) area. PDO is a term used to characterize
      foodstuffs produced and prepared in a given geographical region by the means of a
      recognized process. A standardization of the traditional smoking procedures and
      an improvement of liquid smoke purification treatments are recommended for
      mozzarella cheese.

PMID- 15237952
TI  - Polymerization and gelation of whey protein isolates at low pH using
      transglutaminase enzyme.
AB  - Dynamic and steady shear rheology is used to examine the synthesis of low-pH
      (approximately 4) whey protein gels obtained through a two-step process. The
      first step involves cross-linking of whey proteins at pH 8 and 50 degrees C using
      transglutaminase enzyme, while the second step entails cold-set acidification of
      the resulting solution using glucono-delta-lactone (GDL) acid. During the first
      step, the sample undergoes enzyme-catalyzed epsilon-(gamma-glutamyl)lysine bond
      formation with a substantial increase in viscosity. Acidification in the second
      step using GDL acid leads to a rapid decrease in pH with a concomitant increase
      in the elastic (G') and viscous (G' ') moduli and formation of a gelled network.
      We examine the large strain behavior of the gel samples using a relatively new
      approach that entails plotting the product of elastic modulus and strain
      (G'gamma) as a function of increasing dynamic strain and looking for a maximum,
      which corresponds to the yield or fracture point. We find the enzyme-catalyzed
      gels to have significantly higher yield/fracture stress and strain compared to
      cold-set gels prepared without enzyme or conventional heat-set gels. In addition,
      the elastic modulus of the enzyme-catalyzed gel is also higher than its non
      enzyme-treated counterpart. These results are discussed in terms of the gel
      microstructure and the role played by the enzyme-induced cross-links.

PMID- 15237953
TI  - Heat-induced changes in the ultrasonic properties of whey proteins.
AB  - The physical aggregation of commercial whey protein isolate (WPI) and purified
      beta-lactoglobulin was studied by ultrasound spectroscopy. Protein samples were
      dialyzed to achieve constant ionic strength backgrounds of 0.01 and 0.1 NaCl, and
      gelation was induced in situ at constant temperatures (from 50 to 75 degrees C)
      or with a temperature ramp from 20 to 85 degrees C. Changes in the ultrasonic
      properties were shown in the early stages of heating, at temperatures below those
      reported for protein denaturation. During heating, the relative ultrasound
      velocity (defined as the difference between sample velocity and reference
      velocity) decreased continuously with temperature, indicating a rearrangement of
      the hydration layer of the protein and an increase in compressibility of the
      protein shell. At temperatures <50 degrees C the ultrasonic attenuation
      decreased, and <65 degrees C both velocity and attenuation differentials showed
      increasing values. A sharp decrease in the relative velocity and an increase in
      the attenuation at 70 degrees C were indications of "classical" protein
      denaturation and the formation of a gel network. Values of attenuation were
      significantly different between samples prepared with 0.01 and 0.1 M NaCl,
      although no difference was shown in the overall ultrasonic behavior. WPI and beta
      lactoglobulin showed similar ultrasonic properties during heating, but some
      differences were noted in the values of attenuation of WPI solutions, which may
      relate to a less homogeneous distribution of aggregates caused by the presence of
      alpha-lactalbumin and other minor proteins in WPI.

PMID- 15237954
TI  - Fluoride content in tea and its relationship with tea quality.
AB  - The tea plant is known as a fluorine accumulator. Fluoride (F) content in fresh
      leaves collected from 14 plantations in China was investigated. The F increased
      with maturity, and the F variation was remarkable in the tender shoots.
      Furthermore, significant negative relationships were observed between F content
      and the content of the quality parameters total polyphenols and amino acids.
      These substances are rich in young leaves and poor in mature ones. With regard to
      quality of tea products, the relationship with F content was studied using 12
      brands of tea products in four categories: green tea, oolong tea, black tea, and
      jasmine tea collected from six provinces. The F level increased with the decline
      in quality and showed good correlation with the quality grades. The results
      suggest that the F content could be used as a quality indicator for tea
      evaluation.

PMID- 15237955
TI  - Distribution and contents of phenolic compounds in eighteen Scandinavian berry
      species.
AB  - Berries contain a wide range of phenolic compounds in different conjugated forms,
      a fact that makes their simultaneous analysis a difficult task. In this work,
      soluble and insoluble phenolic compounds were identified and quantified in 18
      species of berries by reversed phase high-performance liquid chromatography
      combined with diode array detection. The analytical results and literature data
      were used for the identification of the predominant conjugated hydroxycinnamic
      acids, flavonol glycosides, and anthocyanins in berries from six families, viz.
      Grossulariaceae, Ericaceae, Rosaceae, Empetraceae, Elaeagnaceae, and
      Caprifoliaceae. The study showed distinctive similarities among berry species of
      the same family in the distribution of conjugated forms of phenolic compounds but
      differences in chromatographic profiles of conjugates and compositions of
      aglycones especially in the case of anthocyanins. The chromatographic profiles of
      chokeberry and the related sweet rowanberry (Rosaceae) were exceptionally
      similar. These data are informative to studies on the authenticity of berry raw
      materials as well as to those on the evaluation of berries as sources of phenolic
      compounds.

PMID- 15237956
TI  - Removal of monomeric phenols in dry mill olive residue by saprobic fungi.
AB  - The dry olive residue (DOR) obtained from the olive oil extraction process has
      toxic components against plants and microorganism growth, particularly monomeric
      phenols. In this investigation nine saprobic fungi were found to be capable of
      completely removing these phenols from the solid after 20 weeks of growth,
      although the rate depended on the type of fungi and phenol. Results showed that
      most of the fungi tested first eliminated o-diphenols and then non-o-diphenols.
      However, some fungi did not follow this trend. Phanerochaete chrysosporium first
      removed hydroxytyrosol and tyrosol and later their glucosides and, in contrast,
      Paecylomyces farinosus hydrolyzed hydroxytyrosol and tyrosol glucosides at the
      first stage, 2 weeks of growth, and then eliminated all monomeric phenols. The
      behavior of this fungus seems of great interest for recovering phenolic
      antioxidants from the DOR. Similarly, differences in DOR decolorization capacity
      among the fungi tested were also observed. Coriolopsis rigida showed the highest
      capacity, followed by Phebia radiata, Pycnoporus cinnabarinus, and Pha.
      chrysosporium. Therefore, both decolorization and monomeric phenol elimination
      pointed out that saprobic fungi could be used to detoxify the DOR obtained from
      the two-phase system of the olive oil extraction process.

PMID- 15237957
TI  - Effect of organic amendments on the retention and mobility of imazaquin in soils.
AB  - The influence of two organic amendments consisting of an urban waste compost
      (SUW) and a commercial amendment from olive mill wastes (OW) was assessed on the
      sorption properties and leaching of the ionizable herbicide imazaquin on four
      soils with different physicochemical characteristics. A loamy sand soil (CR), a
      loam soil (P44), a silt loam soil (AL), and a clay soil (TM), with low-medium
      organic matter contents, were chosen. Sorption-desorption experiments were
      performed on the original soils and on a mixture of these soils with the organic
      amendments at a rate of 6.25% (w/w). These mixtures were used just after
      preparation and after aging for 3 months. Imazaquin adsorption was higher on AL
      soil because of its high content of amorphous iron oxides, whereas it was related
      to the soils' organic matter (OM) contents on TM and CR soils and to acid pH on
      P44 soil. Addition of exogenous OM to soils caused a decrease in the adsorption
      of the herbicide with the only exception of CR soil, due to blocking of
      adsorptive surfaces and/or equilibrium pH rise. The extent of this decrease was
      dependent only on the nature of the added amendment on AL soil. The adsorbed
      amounts of imazaquin on aged organic fertilized soils were usually fairly close
      to that on original soils. Results of soil column experiments indicate that
      addition of exogenous organic matter cannot be considered as a regular practice
      for retarded movement of imazaquin.

PMID- 15237958
TI  - Treatment of cork process wastewater by a successive chemical-physical method.
AB  - In cork processing, the operation of boiling the raw cork generates large volumes
      of wastewater which are more often than not released directly into the
      environment untreated. Even when the wastewater is treated, this is usually by
      retention in evaporation ponds. This procedure, however, causes bad odors and may
      pollute surface water and groundwater. The present study evaluates a
      physicochemical method involving Fenton oxidation and coagulation/flocculation
      for the removal of chemical oxygen demand (COD), total polyphenols (TP), and
      aromatic compounds (A) from cork manufacturing process wastewater. The
      experimental variables studied were the dosages of iron salts (from 0.001 to 0.2
      mol/L) and hydrogen peroxide (between 0.06 and 1 mol/L). The integrated Fenton
      coagulation/flocculation process reduced the COD of the effluent by from 22% to
      85%. The removal of total polyphenols ranged from 4% to 98%, and of aromatic
      compounds from 2% to 97%. A further two experiments were performed modifying the
      manner in which the reagents were added, splitting the reagent dose (of hydrogen
      peroxide and ferrous salt) into two and three fractions. Finally, an economic
      study was made of the chemical costs deriving from the application of this
      purification system. The cost of a treatment with an [H2O2](o)/COD(o) ratio of
      1.8 g/g (splitting the reagent dose into three fractions) that yields a COD
      removal of 73% was estimated to be 11.5 euros/m(3) of wastewater.

PMID- 15237959
TI  - Quantitative studies and sensory analyses on the influence of cultivar, spatial
      tissue distribution, and industrial processing on the bitter off-taste of carrots
      (Daucus carota l.) and carrot products.
AB  - Although various reports pointed to 6-methoxymellein (1) as a key player
      imparting the bitter taste in carrots, activity-guided fractionation experiments
      recently gave evidence that not this isocoumarin but bisacetylenic oxylipins
      contribute mainly to the off-taste. Among these, (Z)-heptadeca-1,9-dien-4,6-diyn
      3-ol (2), (Z)-3-acetoxy-heptadeca-1,9-dien-4,6-diyn-8-ol (3), and (Z)-heptadeca
      1,9-dien-4,6-diyn-3,8-diol (falcarindiol, 4) have been successfully identified.
      In the present study, an analytical procedure was developed enabling an accurate
      quantitation of 1-4 in carrots and carrot products. To achieve this, (E)
      heptadeca-1,9-dien-4,6-diyn-3,8-diol was synthesized as a suitable internal
      standard for the quantitative analysis of the bisacetylenes. On the basis of
      taste activity values, calculated as the ratio of the concentration and the human
      sensory threshold of a compound, a close relationship between the concentration
      of 4 and the intensity of the bitter off-taste in carrots, carrot puree, and
      carrot juice was demonstrated, thus showing that compound 4 might offer a new
      analytical measure for an objective evaluation of the quality of carrot products.
      Quantitative analysis on the intermediate products in industrial carrot
      processing revealed that removing the peel as well as green parts successfully
      decreased the concentrations in the final carrot puree by more than 50%.

PMID- 15237960
TI  - Qualitative determination of volatile compounds and quantitative evaluation of
      safranal and 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde (HTCC) in
      Greek saffron.
AB  - Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde) is the main
      component of saffron's essential oil. It was obtained using microsimultaneous
      hydro distillation-extraction (MSDE) and by ultrasound-assisted extraction (USE),
      which is a mild method. 4-Hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde
      (HTCC) is a precursor of safranal and was obtained in considerable amounts only
      by USE. Five C(13)-norisoprenoids were found in saffron for the first time. Using
      a gas chromatography technique, safranal and HTCC were quantified from Greek
      saffron samples. The quantity of safranal isolated by MSDE ranged between 288.1
      and 687.9 mg/100 g of saffron, whereas in the case of USE safranal and HTCC
      ranged between 40.7 and 647.7 mg/100 g of saffron and between 41.7 and 397.7
      mg/100 g of saffron, respectively. Freeze-drying was also tested as an
      alternative drying method. Over years of storage at 4 degrees C the quantity of
      safranal remained mostly constant while the quantity of HTCC decreased over the
      same periods.

PMID- 15237961
TI  - Investigation of volatiles in Charentais cantaloupe melons (Cucumis melo Var.
      cantalupensis). Characterization of aroma constituents in some cultivars.
AB  - Volatile compounds of 15 Charentais melon cultivars, known to exhibit differences
      in their ripening behaviors and in their storage lives (wild, mid, and long shelf
      life), were investigated. Twenty-eight volatiles (11 esters, 8 sulfur compounds,
      6 alcohols, and 3 carbonyl compounds) were isolated by direct dichloromethane
      extraction and analyzed by means of GC-MS and GC-FID. A considerable reduction in
      the aroma profile was observed for the long shelf life cultivars, in which total
      volatiles were 49-87% lower than in the wild or mid shelf life melons. Most of
      the esters such as ethyl 2-methylbutyrate, ethyl butyrate, ethyl hexanoate, hexyl
      acetate, and butyl acetate and sulfur compounds such as ethyl 2
      (methylthio)acetate, 2-methylthioethanol, ethyl 3-(methylthio)propanoate, 3
      (methylthio)propyl acetate, and 3-(methylthio)propanol with low odor values were
      2-30-fold lower in long shelf life cultivars than in the others. Discrimination
      of long shelf life cultivars from wild and mid shelf life melons was achieved by
      statistical treatment of the data by principal component and variance analysis.

PMID- 15237962
TI  - Effect of Schizosaccharomyces pombe on aromatic compounds in dry sherry wines
      containing high levels of gluconic acid.
AB  - Volatile compounds have been determined in control dry sherry wines and those
      supplemented with gluconic acid, which were inoculated with the
      Schizosaccharomyces pombe 1379 (ATCC 26760) yeast strain. These compounds were
      grouped, according to volatiles exhibiting the identical odor quality, into nine
      groups of the same odor character (aromatic series) as a way of establishing the
      aroma profile for the studied wines. Control and supplemented wines showed
      changes in the balsamic, spicy, roasty, and fruity aromatic series, and tasters
      judged the aroma as typical of wines subjected to biological aging. This fission
      yeast may be used as a treatment to reduce gluconic acid contents in wines
      obtained from rotten grapes, making feasible the incorporation of these wines
      into the biological aging process. In addition, this procedure may also help to
      accelerate the traditional biological aging in sherry winemaking due to the
      contribution of some specific compounds by S. pombe to the wine.

PMID- 15237963
TI  - Detection of genetically modified soybean using peptide nucleic acids (PNAs) and
      microarray technology.
AB  - Peptide nucleic acid (PNA) microarrays for the detection of Roundup Ready
      soybeans in food have been prepared. PNA probes are known to be more efficient
      and selective in binding DNA sequences than the analogous oligonucleotides and
      are very suitable to be used for diagnostics in food. PNAs of different lengths
      were carefully designed and synthesized by solid-phase synthesis on an automatic
      synthesizer adopting the BOC strategy. PNAs were purified by HPLC and
      characterized by HPLC/MS. The probes were spotted on a functionalized surface to
      produce a microarray to be hybridized with PCR products. DNA extracted from
      reference material was amplified using Cy3- and Cy5-labeled primers, and the
      fluorescent PCR products obtained were hybridized on the microarray. Two
      protocols were adopted: the hybridization with dsDNA or with ssDNA obtained by
      digestion with the enzyme lambda exonuclease. The best results were obtained
      using a 15-mer PNA probe in combination with the ssPCR product derived from
      enzymatic digestion. The method was applied to the analysis of a sample of
      certified transgenic soybean flour.

PMID- 15237964
TI  - Allergenic properties of roasted peanut allergens may be reduced by peroxidase.
AB  - Peanut allergy is a public health issue. The culprits are the peanut allergens.
      Reducing the allergenic properties of these allergens or proteins will be
      beneficial to allergic individuals. In this study, the objective was to determine
      if peroxidase (POD), which catalyzes protein cross-linking, reduces the
      allergenic properties of peanut allergens. In the experiments, protein extracts
      from raw and roasted defatted peanut meals at pH 8 were incubated with and
      without POD in the presence of hydrogen peroxide at 37 degrees C for 60 min. The
      POD-treated and untreated samples were then analyzed by SDS-PAGE, western blots,
      and competitive inhibition ELISA. IgE binding or allergenicity was determined in
      blots and ELISA. Results showed that POD treatment had no effect on raw peanuts
      with respect to protein cross-linking. However, a significant decrease was seen
      in the levels of the major allergens, Ara h 1 and Ara h 2, in roasted peanuts
      after POD treatment. Also, polymers were formed. Despite this, a reduction in IgE
      binding was observed. It was concluded that POD induced the cross-linking of
      mainly Ara h 1 and Ara h 2 from roasted peanuts and that, due to POD treatment,
      IgE binding was reduced. The finding indicates that POD can help reduce the
      allergenic properties of roasted peanut allergens.

PMID- 15237965
TI  - Reduced immunogenicity of beta-lactoglobulin by conjugation with acidic
      oligosaccharides.
AB  - Bovine beta-lactoglobulin (beta-LG) was conjugated with the acidic
      oligosaccharides, alginic acid oligosaccharide (ALGO) and phosphoryl
      oligosaccharides (POs) by the Maillard reaction to reduce the immunogenicity of
      beta-LG. The molar ratios of beta-LG to ALGO and POs in the conjugates were 1:6
      and 1:8. The carbohydrate-binding sites in the beta-LG-ALGO conjugate were
      partially identified to be (60)Lys, (77)Lys, (100)Lys, (138)Lys, and (141)Lys.
      The isoelectric point of each conjugate was lower than that of beta-LG. CD
      spectra indicated that the secondary structure of beta-LG was almost maintained
      after conjugation. The results of fluorescence studies indicated that the
      conformation around Trp had not changed in each conjugate and that the surface of
      each conjugate was covered with a saccharide chain. Structural analyses with
      monoclonal antibodies indicated that the conformation around (8)Lys-(19)Trp (beta
      sheet, random coil, short helix) in the conjugates had changed, whereas the
      native structure was maintained around (15)Val-(29)Ile (beta-sheet) and (125)Thr
      (135)Lys (alpha-helix). The beta-LG-ALGO and beta-LG-POs conjugates maintained 77
      and 70% of the retinol binding activity of beta-LG. Conjugation with ALGO and POs
      substantially enhanced the thermal stability of beta-LG. The anti-beta-LG
      antibody response was markedly reduced after immunization with both conjugates in
      BALB/c, C57BL/6, and C3H/He mice. B cell epitopes of beta-LG and the conjugate
      recognized in these mice were determined with 15-mer multipin peptides, and the
      linear epitope profiles of the conjugates were found to be similar to those of
      beta-LG, whereas the antibody response to each epitope was dramatically reduced.
      In particular, effective reduction of the antibody response was observed in the
      vicinity of the carbohydrate-binding sites. Conjugation of beta-LG with these
      acidic oligosaccharides was effective in reducing the immunogenicity of beta-LG.
      The conjugates obtained in this study are edible, so they would be very useful
      for food application.

PMID- 15237966
TI  - Rapid softening of acidified peppers: effect of oxygen and sulfite.
AB  - Evidence was found for two previously unreported, nonenzymatic reactions that
      affected texture retention in acidified red bell peppers. First, oxygen was found
      to cause rapid softening of the pepper tissue such that it lost at least 40% of
      the initial tissue firmness within 2 weeks after acidification. Second, sulfite
      added to the acidified peppers prevented the softening caused by oxygen. Combined
      addition of sulfite and calcium chloride resulted in better retention of tissue
      firmness during extended storage than the addition of either component by itself.

PMID- 15237967
TI  - Role of continuous phase protein on the oxidative stability of fish oil-in-water
      emulsions.
AB  - Whey protein isolate (WPI), soy protein isolate (SPI), and sodium caseinate (CAS)
      can inhibit lipid oxidation when they produce a positive charge at the interface
      of emulsion droplets. However, when proteins are used to stabilize oil-in-water
      emulsions, only a fraction of them actually absorb to the emulsion droplets, with
      the rest remaining in the continuous phase. The impact of these continuous phase
      proteins on the oxidative stability of protein-stabilized emulsions is not well
      understood. WPI-stabilized menhaden oil-in-water emulsions were prepared by high
      pressure homogenization. In some experiments WPI was removed from the continuous
      phase of the emulsions through repeated centrifugation and resuspension of the
      emulsion droplets (washed emulsion). Unwashed emulsions were more oxidatively
      stable than washed emulsions at pH 7.0, suggesting that continuous phase proteins
      were antioxidative. The oxidative stability of emulsions containing different
      kinds of protein in the continuous phase decreased in the order SPI > CAS > WPI,
      as determined by both hydroperoxide and headspace propanal formation. Iron
      binding studies showed that the chelating ability of the proteins decreased in
      the order CAS > SPI > WPI. The free sulfhydryls of both WPI and SPI were involved
      in their antioxidant activity. This research shows that continuous phase proteins
      could be an effective means of protecting omega-3 fatty acids from oxidative
      deterioration.

PMID- 15237968
TI  - Expression and nucleotide sequence of an INS (3) P1 synthase gene associated with
      low-phytate kernels in maize (Zea mays L.).
AB  - Most of the phosphorus (P) in maize (Zea mays L.) kernels is in the form of
      phytic acid. A low phytic acid (lpa) maize mutant, lpa1-1, displays levels
      reduced by 66%. A goal of genetic breeding is development of low phytic acid
      feedstocks to improve P nutrition of nonruminant animals and reduce the adverse
      environmental impacts of excess P in manure. The genetic basis of the lpa1-1
      mutation is not known, but previous genetic mapping has shown both the mutant
      phenotype and the Ins (3) P(1) synthase (MIPS) gene, which encodes the first
      enzyme, myo-inositol phosphate synthase, in the phytic acid biosynthetic pathway,
      map to the same chromosomal region in maize. Research was conducted to determine
      the expression of the MIPS gene in lpa1-1 and wild-type kernels with similar
      genetic backgrounds and to ascertain if variation in the MIPS coding sequence
      could be inferred to be the basis of the mutation. MIPS enzyme activity
      determined by TLC was reduced 2-3-fold in mutant kernels. RT-PCR-based
      experiments using primers specific for the 1S-MIPS sequence indicated gene
      expression was reduced 50-60% in the mutant. Sequence analysis of the MIPS
      genomic sequence revealed 10 exons and 9 introns that are identical in both
      mutant and wild-type developing kernels. These findings support an association
      between reduced MIPS gene activity and low phytic acid content, but additional
      research should examine the promoter, the 5'UTR, or transcriptional controlling
      elements of the MIPS gene to ascertain the possible presence of a genetic lesion
      in those regions.

PMID- 15237970
TI  - Chemical moieties and interactions involved in the binding of zearalenone to the
      surface of Lactobacillus rhamnosus strains GG.
AB  - Viable, heat-and acid-killed Lactobacillus rhamnosus strain GG (LGG) has shown
      high binding properties with zearalenone (ZEN). To identify the type of chemical
      moieties and interactions involved in binding with the ZEN, LGG was subjected to
      different chemical and enzymatical treatments, prior to the binding experiments.
      Pretreating the viable, heat- and acid-killed bacteria with m-periodate
      significantly decreased ZEN binding, suggesting that ZEN binds predominantly to
      carbohydrate components. Pretreatment with Pronase E had no effect on the ability
      of viable cells to bind ZEN, however, a reduction in the binding of ZEN by heat-
      and acid-killed cells, suggesting that the new binding sites exposed by heat or
      acid are proteins in nature. Pretreatment with urea also decreased binding,
      suggesting that hydrophobic interactions play a role in ZEN binding. The binding
      of ZEN in concentrations ranging from 0.79 to 62.82 microM and its subsequent
      dissociation by repetitive aqueous washes was also studied. The binding sites of
      the bacteria were not saturated by the maximum ZEN concentration studied.

PMID- 15237972
TI  - Asymmetric 1,4-hydrosilylations of alpha,beta-unsaturated esters.
AB  - Complexing catalytic amounts of CuH with a nonracemic JOSIPHOS or SEGPHOS ligand,
      together with stoichiometric PMHS, leads to exceedingly efficient and highly
      enantioselective 1,4-reductions of beta,beta-disubstituted enoates and lactones.
      An unprecedented substrate-to-ligand ratio of 7700:1 for this type of reaction is
      documented.

PMID- 15237969
TI  - Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea,
      on neutrophil chemotaxis in vitro and in vivo.
AB  - The effect of (-)-epigallocatechin 3-gallate (EGCG), a major polyphenol of green
      tea, on neutrophil migration has been studied using multiwell-type Boyden
      chambers in vitro and a fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA)
      induced rat allergic inflammation model in vivo. EGCG inhibited rat neutrophil
      chemotaxis toward cytokine-induced neutrophil chemoattractant-1 (CINC-1) in a
      concentration-dependent manner. In addition, CINC-1-induced neutrophil chemotaxis
      was suppressed by the pretreatment of rat neutrophils with EGCG at the
      concentration over 15 microg/mL. EGCG caused concentration-dependent suppression
      of the transient increase in CINC-1-induced intracellular free calcium level in
      both rat neutrophils and rat CXC chemokine receptor 2 (CXCR2)-transfected HEK 293
      cells. EGCG inhibited CINC-1 production by IL-1beta-stimulated rat fibroblasts
      (NRK-49F cells) and lipopolysaccharide-stimulated rat macrophages at the
      concentration over 50 microg/mL, a comparatively high concentration. Oral
      administration of EGCG (1.0 mg or 1.5 mg/rat) at 1 h before the challenge with
      FITC-OVA suppressed neutrophil infiltration into the air pouch (inflammatory
      site) in the air-pouch type FITC-OVA-induced allergic inflammation in rats.
      Chemokine levels in the pouch fluids, however, were not influenced by EGCG
      administration. The results suggest that EGCG suppressed neutrophil infiltration
      by a direct action on neutrophils, but not by indirect actions, including the
      suppression of chemokine production at the inflammatory site.

PMID- 15237973
TI  - An unusual mechanism of glycoside hydrolysis involving redox and elimination
      steps by a family 4 beta-glycosidase from Thermotoga maritima.
AB  - Among the numerous well-characterized families of glycosidases, family 4 appears
      to be the anomaly, requiring both catalytic NAD+ and a divalent metal for
      activity. The unusual cofactor requirement prompted the proposal of a mechanism
      involving key NAD+-mediated redox steps as well as elimination of the glycosidic
      oxygen. Primary kinetic isotope effects for the 2- and 3-deutero substrate
      analogues, isotopic exchange with solvent, and structural analysis of a 6-phospho
      beta-glucosidase, BglT (E.C. 3.2.1.6), provided evidence in support of the
      proposed mechanism, which has striking resemblances to that of the sugar
      dehydratases. Furthermore, analysis of the stereochemical outcome indicated that
      family 4 enzymes are retaining glycosidases.

PMID- 15237974
TI  - A surprising dipolar cycloaddition provides ready access to aminoglycosides.
AB  - This contribution describes the results of a new research effort in our
      laboratory aimed at the synthesis of novel aminoglycosides and amino-C
      glycosides. Despite the importance of such compounds, and the previous
      development of some methodological solutions, this remains an important area of
      research. Notable features of our approach, which is distinct from and
      complementary to previous efforts, are the following: (1) Reliance on a
      surprising and unprecedented formation of glycal triazolines via an inverse
      electron demand dipolar cycloaddition of glucal. We believe this desirable
      transformation has not previously been discovered because of the unusual
      selection of substrates and solvent required. (2) Very mild reaction conditions.
      An initial thermal cycloaddition is carried out in an inert solvent, the
      triazoline generated is photochemically converted to a reactive aziridine, and
      the crude aziridine undergoes ring opening at room temperature in the presence of
      a nucleophile and a mild Lewis acid catalyst. (3) Formation of products lacking
      an N-acyl group, allowing ready synthesis of novel glucosamine derivatives.

PMID- 15237975
TI  - Strong blue photoluminescence and ECL from OH-terminated PAMAM dendrimers in the
      absence of gold nanoparticles.
AB  - A product showing strong blue photoluminescence was obtained by oxidation of OH
      terminated PAMAM dendrimers, such as G4-OH, G2-OH, and G0-OH, with HAuCl4 or
      (NH4)2S2O8. The fluorescence emission spectrum peaked at 450 nm, while the
      excitation maximum was at 380 nm, independent of the generation of dendrimer. The
      product also shows two weak electrogenerated chemiluminescence (ECL) signals upon
      cycling the potential between about 1.2 and -1.7 V.

PMID- 15237976
TI  - Time-resolved electrochemical detection of discrete adsorption events.
AB  - Individual binding events are observed using amperometric detection. Discrete
      steps in the microelectrode amperometric response correspond to the adsorption of
      single microspheres on the electrode surface.

PMID- 15237977
TI  - A predictive pattern of computed barriers for C-h hydroxylation by compound I of
      cytochrome p450.
AB  - The communication presents DFT calculations of 10 different C-H hydroxylation
      barriers by the active species of the enzyme cytochrome P450. The work
      demonstrates the existence of an excellent barrier-bond energy correlation. The
      so-obtained equation of the straight line is demonstrated to be useful for
      predicting barriers of related C-H activation processes, as well as for assessing
      barrier heights within the protein environment. This facility is demonstrated be
      estimating the barrier of camphor hydroxylation by P450cam.

PMID- 15237978
TI  - Pyrene-labeled oligodeoxynucleotide probe for detecting base insertion by excimer
      fluorescence emission.
AB  - Novel ODN probes for insertion polymorphism detection have been devised. The ODN
      probes labeled with two pyrene chromophores emit strong excimer fluorescence when
      hybridized with DNA containing one inserted base. This method is useful for the
      determination of the presence/absence of insertion polymorphisms located at a
      specific site on the target DNA.

PMID- 15237979
TI  - Bridging the gap between homogeneous and heterogeneous catalysis: ortho/para H(2)
      conversion, hydrogen isotope scrambling, and hydrogenation of olefins by
      Ir(CO)Cl(PPh(3))(2).
AB  - Some transition metal complexes are known to catalyze ortho/para hydrogen
      conversion, hydrogen isotope scrambling, and hydrogenation reactions in liquid
      solution. Using the example of Vaska's complex, we present here evidence by NMR
      that the solvent is not necessary for these reactions to occur. Thus, solid
      frozen solutions or polycrystalline powdered samples of homogeneous catalysts may
      become heterogeneous catalysts. Comparative liquid- and solid-state studies
      provide novel insight into the reaction mechanisms.

PMID- 15237980
TI  - A four-electron O(2)-electroreduction biocatalyst superior to platinum and a
      biofuel cell operating at 0.88 V.
AB  - O2 was electroreduced to water, at a true-surface-area-based current density of
      0.5 mA cm-2, at 37 degrees C and at pH 5 on a "wired" laccase bioelectrocatalyst
      coated carbon fiber cathode. The polarization (potential vs the reversible
      potential of the O2 /H2O half-cell in the same electrolyte) of the cathode was
      only -0.07 V, approximately one-fifth of the -0.37 V polarization of a smooth
      platinum fiber cathode, operating in its optimal electrolyte, 0.5 M H2SO4. The
      bioelectrocatalyst was formed by "wiring" laccase to carbon through an electron
      conducting redox hydrogel, its redox functions tethered through long and flexible
      spacers to its cross-linked and hydrated polymer. Incorporation of the tethers
      increased the apparent electron diffusion coefficient 100-fold to (7.6 +/- 0.3) x
      10-7 cm 2 s-1. A miniature single-compartment glucose-O2 biofuel cell made with
      the novel cathode operated optimally at 0.88 V, the highest operating voltage for
      a compartmentless miniature fuel cell.

PMID- 15237981
TI  - A small aptamer with strong and specific recognition of the triphosphate of ATP.
AB  - We report the in vitro selection of an RNA-based ATP aptamer with the ability to
      discriminate between adenosine ligands based on their 5' phosphorylation state.
      Previous selection of ATP aptamers yielded molecules that do not significantly
      discriminate between ligands at the 5' position. By applying a selective pressure
      that demands recognition of the 5' triphosphate, we obtained an aptamer that
      binds to ATP with a Kd of approximately 5 muM, and to AMP with a Kd of
      approximately 5.5 mM, a difference of 1100-fold. This aptamer demonstrates the
      ability of small RNAs to interact with negatively charged moieties.

PMID- 15237983
TI  - AFM-induced amine deprotection: triggering localized bond cleavage by application
      of tip/substrate voltage bias for the surface self-assembly of nanosized
      dendritic objects.
AB  - An alpha,alpha-dimethyl-3,5-dimethoxybenzyloxycarbonyl (DDZ)-protected amine
      monolayer can be selectively deprotected by the application of a voltage bias
      from a conducting AFM tip to afford localized nanoscale patterns that can be
      visualized by self-assembly of dendritic molecular objects with terminal
      carboxylic acid groups and different aspect ratios.

PMID- 15237982
TI  - A polysaccharide carrier for immunostimulatory CpG DNAs to enhance cytokine
      secretion.
AB  - A beta-(1 --> 3)-d-glucan schizophyllan (SPG) forms a stoichiometric complex with
      some polynucleotides. This communication describes our attempt to apply the SPG
      complex to deliver CpG DNA to endosomes to enhance cytokine secretion. To
      increase cellular uptake, we introduced spermine, arginine-glycine-aspartic acid
      tripeptide, octaarginine, or cholesterol to the SPG side chain. The chemically
      modified SPG showed essentially no cytotoxicity. When CpG DNA complex made
      therefrom was exposed to macrophages, dramatic enhancement in the cytokine
      secretion was observed. It increased 5-10 times from the naked dose and 100 times
      from the background. This performance promises that SPG can be an excellent
      carrier for CpG DNA.

PMID- 15237984
TI  - Direct measurement of the transbilayer movement of phospholipids by sum-frequency
      vibrational spectroscopy.
AB  - The direct measurement of the transbilayer movement of 1,2-distearoyl-sn-glycero
      3-phosphocholine (DSPC) in a planar supported lipid bilayer (PSLB) at the fused
      silica/D2O interface was obtained with sum-frequency generation (SFG) vibrational
      spectroscopy. The intrinsic sensitivity of SFG to the symmetry of an interface
      was used to measure the asymmetric distribution of DSPC and perdeuterated DSPC
      (DSPC-d83) lipids in asymmetrically prepared DSPC/DSPC-d83 PSLBs. Changes in the
      membrane lipid composition due to exchange between leaflets was monitored by
      measuring the decay in the CH3 symmetric stretch intensity at 2875 cm-1 with
      time. The activation energy for transverse motion was determined directly from
      spectral relaxation measurements at several temperatures and was determined to be
      206 +/- 18 kJ/mol. At room temperature (25 degrees C) the half-time of lipid flip
      flop was calculated to be approximately 25 days. At 51 degrees C, only 7 degrees
      C below the main phase-transition temperature of DSPC, the half-time decreases to
      25 min. These results have important implications for understanding the
      transbilayer movement of lipids in biological membranes.

PMID- 15237985
TI  - (57)Fe ENDOR spectroscopy on the iron-sulfur cluster involved in substrate
      reduction of heterodisulfide reductase.
AB  - Heterodisulfide reductase (Hdr) from methanogenic archea is an iron-sulfur
      protein that catalyzes the reversible two-electron reduction of the mixed
      disulfide CoM-S-S-CoB to the thiol coenzymes, coenzyme M (CoM-SH) and coenzyme B
      (CoB-SH). It is unusual that this enzyme uses an iron-sulfur cluster to mediate
      disulfide reduction in two one-electron steps via site-specific cluster
      chemistry. Upon half-reaction of the oxidized enzyme with CoM-SH in the absence
      of CoB-SH, an iron-based paramagnetic intermediate is formed, designated CoM-Hdr.
      In this Communication we report 57Fe pulsed ENDOR at two very different
      frequencies, 9 and 94 GHz, that identify the iron sites of CoM-Hdr. We find
      direct evidence for a [4Fe-4S]3+ cluster, and we determine the sign of the 57Fe
      hyperfine couplings. The 57Fe isotropic hfc values suggest a complex interaction
      between the cluster and the CoM-SH substrate.

PMID- 15237986
TI  - Hydrogen titanate nanofibers covered with anatase nanocrystals: a delicate
      structure achieved by the wet chemistry reaction of the titanate nanofibers.
AB  - Hydrogen titanate nanofibers synthesized by a hydrothermal reaction, are
      chemically reactive, readily reacting with dilute acid. This reaction is a
      topochemical process in which in situ phase transition from H-titanate to anatase
      takes place and the product retains the fibril morphology. The extent of this
      reaction can be precisely controlled, allowing us to achieve a delicate composite
      structure at nanoscale: long titanate fibers of 40-100 nm thick and up to 30 mum
      long covered with anatase nanocrystals of 10-30 nm. The structure has desired
      photocatalytic properties and can be separated readily after use. This study
      demonstrates new opportunities to create delicate inorganic nanostructures with
      advanced functions by wet chemical reactions.

PMID- 15237987
TI  - Iridium complex-catalyzed highly enantio- and diastereoselective [2+2+2]
      cycloaddition for the synthesis of axially chiral teraryl compounds.
AB  - An asymmetric [2+2+2] cycloaddition of an alpha,omega-diyne, possessing ortho
      substituted aryl groups on its terminus, and a monoalkyne with oxygen
      functionalities gave various axially chiral teraryl compounds. The coupling
      proceeded with extremely high enantio- (>99.5% ee) and diastereoselectivities
      (dl/meso = >95/5) when catalyzed by an iridium-chiral phosphine complex. As the
      products were readily transformed into diol compounds by deprotection without
      racemization, the present procedure provides access to a new chiral pool of diol
      compounds with C2 symmetry.

PMID- 15237988
TI  - First principles investigation of vancomycin and teicoplanin binding to bacterial
      cell wall termini.
AB  - The recent rise of vancomycin-resistant enterococci (VRE) has given new impetus
      to the study of the binding between glycopeptide antibiotics and bacterial cell
      wall termini. Here, we report on an extensive first principles investigation of
      the binding of vancomycin and teicoplanin with d-Ala-d-Lac (characteristic of
      VREs) and d-Ala-d-Ala (characteristic of non-VREs). Binding of both antibiotics
      to d-Ala-d-Ala was found to be stronger by about 3-5 kcal/mol and due primarily
      to the oxygen-oxygen lone-pair repulsion characteristic of the antibiotic/d-Ala-d
      Lac complex. These results are in good agreement with recent experimental
      findings.

PMID- 15237989
TI  - All-optical orientation of photoisomerizable octupolar zinc(II) complexes in
      polymer films.
AB  - A new type of 4,4'-bis(styryl)-2,2'-bipyridine functionalized by a dialkylamino
      azobenzene group has been prepared. This ligand has allowed the preparation of
      photoisomerizable octupolar tris(bipyridyl)zinc(II) complexes and the
      corresponding star-shaped polymer by atom transfer radical polymerization (ATRP)
      of methyl methacrylate (MMA). The photoisomerization properties of such new
      metallo-chromophores have been studied. The macroscopic molecular orientation of
      the corresponding doped and grafted NLO-polymer films is reported for the first
      time.

PMID- 15237990
TI  - New beginnings for matrix metalloproteinase inhibitors: identification of high
      affinity zinc-binding groups.
AB  - In an effort to identify promising non-hydroxamate inhibitors of matrix
      metalloproteinases (MMPs), several new zinc-binding groups (ZBGs) based on
      pyrone, pyrothione, hydroxypyridinone, and hydroxypyridinethione chelators have
      been examined. Structural studies with tris(pyrazolyl)borate model complexes show
      that these ligands bind to the MMP active site zinc(II) ion in a bidentate
      fashion, similar to that found with hydroxamate-based inhibitors. Fluorescence-
      and colorimetric-based enzyme assays have been used to determine the IC50 values
      for these ZBGs against MMP-3; mixed O,S-donor ligands were found to be remarkably
      potent, with IC50 values as much as 700-fold lower than that found for
      acetohydroxamic acid. Inhibitory activity was found to parallel metal binding
      affinity as determined in titrations with model complexes. These results
      demonstrate that MPIs based on new ZBGs are feasible and may indeed improve the
      overall performance of inhibitors designed against these important medicinal
      targets.

PMID- 15237991
TI  - A diversity-oriented strategy for the construction of tetrasubstituted pyrroles
      via coupled domino processes.
AB  - A new microwave-assisted rearrangement of 1,3-oxazolidines scaffolds is the basis
      for a new, metal-free, direct, and modular construction of tetrasubstituted
      pyrroles from terminal-conjugated alkynes, aldehydes, and primary amines. This
      new reaction manifold entails two linked domino processes in a one-pot manner
      with both atom- and bond-efficiency and under very simple and environment
      friendly experimental conditions.

PMID- 15237992
TI  - Isotopomeric polymorphism.
AB  - The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP)
      crystallizes in a triclinic space group. If the same complex is synthesized from
      deuterated pentachlorophenol (4MPPCP-d1), it crystallizes in an entirely
      different monoclinic polymorph. Solid-state NMR of samples synthesized with a
      full range of deuteration levels, crystallized from solution or the melt, and in
      the presence or absence of seeds confirms that the isotopomers indeed have
      different thermodynamically stable crystal structures. The phenomenon is
      apparently due to very different hydrogen bond strengths between the two
      polymorphs.

PMID- 15237993
TI  - One-step synthesis of FePt nanoparticles with tunable size.
AB  - A one-step synthesis of FePt nanoparticles is reported. The size, composition,
      and shape of the particles are controlled by varying the synthetic parameters
      such as molar ratio of stabilizers to metal precursor, addition sequence of the
      stabilizers and metal precursors, heating rate, heating temperature, and heating
      duration. An assembly of large (6 nm or greater) FePt nanoparticles, especially
      oxide-coated FePt nanoparticles, can sustain higher temperature (up to 650
      degrees C) annealing without noticeable particle sintering. Room temperature
      coercivity of an assembly containing discrete FePt dots can reach as high as 1.3
      T, a value that is suitable for hard magnetic applications.

PMID- 15237994
TI  - Total synthesis, structure revision, and absolute configuration of (+)
      yatakemycin.
AB  - The total synthesis of the reported structure 2 for yatakemycin, an exceptionally
      potent, naturally occurring antitumor agent disclosed in 2003, and its lack of
      correlation with the natural product are detailed. On the basis of spectroscopic
      distinctions between 2 and yatakemycin, the natural product structure was
      reformulated as 3, now bearing a thiomethyl ester versus thioacetate in the left
      hand subunit. Total synthesis of 3 provided a compound nearly identical to but
      still subtly distinct from the natural product. A second reformulation of the
      yatakemycin structure as 1, incorporating the alternatively substituted right
      hand subunit as well as the initial thiomethyl ester reformulation, was confirmed
      by total synthesis of both (+)- and ent-(-)-1 in studies that also unambiguously
      established the absolute configuration of the natural product.

PMID- 15237995
TI  - Evidence for a post-translational modification, aspartyl aldehyde, in a
      photosynthetic membrane protein.
AB  - In oxygenic photosynthesis, photosystem II (PSII) carries out the oxidation of
      water and reduction of plastoquinone. Three PSII subunits contain reactive groups
      that covalently bind amines and phenylhydrazine. It has been proposed that these
      reactive groups are carbonyl-containing, co- or post-translationally modified
      amino acids. To identify modified amino acid residues in one of the PSII subunits
      (CP47), tandem mass spectrometry was performed. Modified residues were affinity
      tagged with either biotin-LC-hydrazide or biocytin hydrazide, which are known to
      label carbonyl groups. The affinity-tagged subunit was isolated by denaturing gel
      electrophoresis, and tryptic peptides were then subjected to affinity
      purification and tandem mass spectrometry. This procedure identified a hydrazide
      labeled peptide, which has the sequence XKEGR. This result is supported by
      quantitative results acquired from peptide mapping and methylamine labeling. The
      gene sequence and these tandem data predict that the first amino acid, X, which
      is labeled with the hydrazide reagent, is a modified form of aspartic acid. On
      the basis of these data, we propose that D348 of the CP47 subunit is post- or co
      translationally modified to give a novel amino acid side chain, aspartyl
      aldehyde.

PMID- 15237996
TI  - Mononuclear nickel(III) and nickel(II) thiolate complexes with intramolecular S-H
      proton interacting with both sulfur and nickel: relevance to the [NiFe]/[NiFeSe]
      hydrogenases.
AB  - Mononuclear, distorted square planar [Ni(II)(ER)(P(o-C(6)H(4)S)(2)(o
      C(6)H(4)SH))](-) (ER = SePh (1), 2-S-C(4)H(3)S (2)) with a S-H proton directly
      interacting with both nickel and sulfur atoms were prepared by reaction of
      [Ni(CO)(SePh)(3)](-)/[Ni(CO)(2-S-C(4)H(3)S)(3)](-) and P(o-C(6)H(4)SH)(3),
      individually. The presence of combinations of intramolecular [Ni-S...H
      SR]/[Ni...H-SR] interactions was verified in the solid state by the observation
      of an IR nu(SH) stretching band (2273 and 2283 cm(-)(1) (KBr) for complexes 1 and
      2, individually) and (1)H NMR spectra (delta 8.079 (d) (CD(2)Cl(2)) and 8.39 (d)
      (C(4)D(8)O) ppm (-SH) for complexes 1 and 2, respectively) and subsequently
      confirmed by X-ray diffraction study. The exo-thiol proton (o-C(6)H(4)SH) in
      complexes 1 and 2 was identified as a D(2)O exchangeable proton from NMR and IR
      studies and was quantitatively removed by Lewis base Et(3)N to yield Ni(II) dimer
      [Ni(II)(P(o-C(6)H(4)S)(3))](2)(2)(-) (5). Instead of the ligand-based oxidation
      to form dinuclear Ni(II) complexes and dichalcogenide, oxidation of THF-CH(3)CN
      solution of complexes 1 and 2 by O(2) resulted in the formation of the
      mononuclear, distorted trigonal bipyramidal [Ni(III)(ER)(P(o-C(6)H(4)S)(3))](-)
      (ER = SePh (3), 2-S-C(4)H(3)S (4)) accompanied by byproduct H(2)O identified by
      (1)H NMR, respectively. The 4.2 K EPR spectra of complexes 3 and 4 exhibiting
      high rhombicities with three principal g values of 2.304, 2.091, and 2.0 are
      consonant with Ni(III) with the odd electron in the d(z)(2) orbital. Complex 3
      undergoes a reversible Ni(III/II) process at E(1/2) = -0.67 V vs Ag/AgCl in MeCN.

PMID- 15237997
TI  - Sequential oxidation of the cubane [4Fe--4S] cluster from [4Fe--4S](-) to [4Fe-
      4S](3+) in Fe(4)S(4)L(n)(-) complexes.
AB  - Gaseous Fe(4)S(n)(-) (n = 4-6) clusters and synthetic analogue complexes,
      Fe(4)S(4)L(n)(-) (L = Cl, Br, I; n = 1-4), were produced by laser vaporization of
      a solid Fe/S target and electrospray from solution samples, respectively, and
      their electronic structures were probed by photoelectron spectroscopy. Low
      binding energy features derived from minority-spin Fe 3d electrons were clearly
      distinguished from S-derived bands. We showed that the electronic structure of
      the simplest Fe(4)S(4)(-) cubane cluster can be described by the two-layer spin
      coupling model previously developed for the [4Fe] cubane analogues. The
      photoelectron data revealed that each extra S atom in Fe(4)S(5)(-) and Fe(4)S(6)(
      ) removes two minority-spin Fe 3d electrons from the [4Fe--4S] cubane core and
      each halogen ligand removes one Fe 3d electron from the cubane core in the
      Fe(4)S(4)L(n)(-) complexes, clearly revealing a behavior of sequential oxidation
      of the cubane over five formal oxidation states: [4Fe--4S](-) --> [4Fe--4S](0) -
      > [4Fe--4S](+) --> [4Fe-4S](2+) --> [4Fe-4S](3+). The current work shows the
      electron-storage capability of the [4Fe--4S] cubane, contributes to the
      understanding of its electronic structure, and further demonstrates the
      robustness of the cubane as a structural unit and electron-transfer center.

PMID- 15237998
TI  - Effects of glycosylation on peptide conformation: a synergistic experimental and
      computational study.
AB  - Asparagine-linked glycosylation, the co-translational covalent attachment of
      carbohydrates to asparagine side chains, has a major effect on the folding,
      stability, and function of many proteins. The carbohydrate composition in mature
      glycoproteins is heterogeneous due to modification of the initial oligosaccharide
      by glycosidases and glycosyltransferases during the glycoprotein passage through
      the endoplasmic reticulum and Golgi apparatus. Despite the diversity of
      carbohydrate structures, the core beta-D-(GlcNAc)(2) remains conserved in all N
      linked glycoproteins. Previously, results from our laboratory showed that the
      molecular composition of the core disaccharide has a critical and unique
      conformational effect on the peptide backbone. Herein, we employ a synergistic
      experimental and computational approach to study the effect of the
      stereochemistry of the carbohydrate--peptide linkage on glycopeptide structure. A
      glycopeptide derived from a hemagglutinin protein fragment was synthesized, with
      the carbohydrate attached to the peptide with an alpha-linked stereochemistry.
      Computational and biophysical analyses reveal that the conformations of the
      peptide and alpha- and beta-linked glycopeptides are uniquely influenced by the
      attached saccharide. The value of computational approaches for probing the
      influence of attached saccharides on polypeptide conformation is highlighted.

PMID- 15237999
TI  - Quantifying the roughness on the free energy landscape: entropic bottlenecks and
      protein folding rates.
AB  - The prediction of protein folding rates and mechanisms is currently of great
      interest in the protein folding community. A close comparison between theory and
      experiment in this area is promising to advance our understanding of the physical
      chemical principles governing the folding process. The delicate interplay of
      entropic and energetic/enthalpic factors in the protein free energy regulates the
      details of this complex reaction. In this article, we propose the use of
      topological descriptors to quantify the amount of heterogeneity in the
      configurational entropy contribution to the free energy. We apply the procedure
      to a set of 16 two-state folding proteins. The results offer a clean and simple
      theoretical explanation for the experimentally measured folding rates and
      mechanisms, in terms of the intrinsic entropic roughness along the populated
      folding routes on the protein free energy landscape.

PMID- 15238000
TI  - UV Raman demonstrates that alpha-helical polyalanine peptides melt to polyproline
      II conformations.
AB  - We examined the 204-nm UV Raman spectra of the peptide XAO, which was previously
      found by Shi et al.'s NMR study to occur in aqueous solution in a polyproline II
      (PPII) conformation. The UV Raman spectra of XAO are essentially identical to the
      spectra of small peptides such as ala(5) and to the large 21-residue
      predominantly Ala peptide, AP. We conclude that the non-alpha-helical
      conformations of these peptides are dominantly PPII. Thus, AP, which is highly
      alpha-helical at room temperature, melts to a PPII conformation. There is no
      indication of any population of intermediate disordered conformations. We
      continued our development of methods to relate the Ramachandran Psi-angle to the
      amide III band frequency. We describe a new method to estimate the Ramachandran
      Psi-angular distributions from amide III band line shapes measured in 204-nm UV
      Raman spectra. We used this method to compare the Psi-distributions in XAO,
      ala(5), the non-alpha-helical state of AP, and acid-denatured apomyoglobin. In
      addition, we estimated the Psi-angle distributions of peptide bonds which occur
      in non-alpha-helix and non-beta-sheet conformations in a small library of
      proteins.

PMID- 15238001
TI  - Critical role of magnesium ions in DNA polymerase beta's closing and active site
      assembly.
AB  - To dissect the effects of the nucleotide-binding and catalytic metal ions on DNA
      polymerase mechanisms for DNA repair and synthesis, aside from the chemical
      reaction, we investigate their roles in the conformational transitions between
      closed and open states and assembly/disassembly of the active site of polymerase
      beta/DNA complexes before and after the chemical reaction of nucleotide
      incorporation. Using dynamics simulations, we find that closing before chemical
      reaction requires both divalent metal ions in the active site while opening after
      the chemical reaction is triggered by release of the catalytic metal ion. The
      critical closing is stabilized by the interaction of the incoming nucleotide with
      conserved catalytic residues (Asp190, Asp192, Asp256) and the two functional
      magnesium ions; without the catalytic ion, other protein residues (Arg180,
      Arg183, Gly189) coordinate the incomer's triphosphate group through the
      nucleotide-binding ion. Because we also note microionic heterogeneity near the
      active site, Mg(2+) and Na(+) ions can diffuse into the active site relatively
      rapidly, we suggest that the binding of the catalytic ion itself is not a rate
      limiting conformational or overall step. However, geometric adjustments
      associated with functional ions and proper positioning in the active site,
      including subtle but systematic motions of protein side chains (e.g., Arg258),
      define slow or rate-limiting conformational steps that may guide fidelity
      mechanisms. These sequential rearrangements are likely sensitively affected when
      an incorrect nucleotide approaches the active site. Our suggestion that subtle
      and slow adjustments of the nucleotide-binding and catalytic magnesium ions help
      guide polymerase selection for the correct nucleotide extends descriptions of
      polymerase pathways and underscores the importance of the delicate conformational
      events both before and after the chemical reaction to polymerase efficiency and
      fidelity mechanisms.

PMID- 15238002
TI  - Water molecule adsorption on short alanine peptides: how short is the shortest
      gas-phase alanine-based helix?
AB  - Water adsorption measurements have been performed under equilibrium conditions
      for unsolvated Ac-A(n)K+H(+) and Ac-KA(n)+H(+) peptides with n = 4 - 10. Previous
      work on larger alanine peptides has shown that two dominant conformations
      (helices and globules) are present for these peptides and that water adsorbs much
      more strongly to the globules than to the helices. All the Ac-KA(n)+H(+) peptides
      studied here (which are expected to be globular) adsorb water strongly, and so do
      the Ac-A(n)K+H(+) peptides with n < 8. However, for Ac-A(n)K+H(+) with n = 8-10
      there is a substantial drop in the propensity to adsorb water. This result
      suggests that Ac-A(8)K+H(+) is the smallest Ac-A(n)K+H(+) peptide to have a
      significant helical content in the gas phase. Water adsorption measurements for
      Ac-V(n)K+H(+) and Ac-L(n)K+H(+) with n = 5-10 suggest that the helix emerges at n
      = 8 for these peptides as well.

PMID- 15238003
TI  - Functional self-assembling bolaamphiphilic polydiacetylenes as colorimetric
      sensor scaffolds.
AB  - Conjugated polymers capable of responding to external stimuli by changes in
      optical, electrical, or electrochemical properties can be used for the
      construction of direct sensing devices. Polydiacetylene-based systems are
      attractive for sensing applications due to their colorimetric response to changes
      in the local environment. Here we present the design, preparation, and
      characterization of self-assembling functional bolaamphiphilic polydiacetylenes
      (BPDAs) inspired by nature's strategy for membrane stabilization. We show that by
      placing polar headgroups on both ends of the diacetylene lipids in a
      transmembranic fashion and by altering the chemical nature of the polar surface
      residues, the conjugated polymers can be engineered to display a range of
      radiation-, thermal-, and pH-induced colorimetric responses. We observed dramatic
      nanoscopic morphological transformations accompanying charge-induced chromatic
      transitions, suggesting that both side-chain disordering and main-chain
      rearrangement play important roles in altering the effective conjugation lengths
      of the poly(ene-yne). These results establish the foundation for further
      development of BPDA-based colorimetric sensors.

PMID- 15238004
TI  - Rearrangements concerted with fragmentation of cyclopropylmethoxychlorocarbene
      and cyclobutoxychlorocarbene in hydrocarbon solvents and Ar matrices.
AB  - Fragmentations of cyclopropylmethoxychlorocarbene (6) and
      cyclobutoxychlorocarbene (10) lead to rearrangments that afford mixtures of
      cyclopropylmethyl chloride (7), cyclobutyl chloride (8), and 3-butenyl chloride
      (9). Isotopic substitution studies show that these rearrangments are accompanied
      by partial exchange of the methylene groups within 6 and 10. Surprisingly, these
      processes that are typical of carbocations persist in hydrocarbon solvents such
      as pentane and cyclohexane-d(12). Quantum chemical calculations reveal that the
      cis-conformers of the incipient oxychlorocarbenes C(4)H(7)OC(..)Cl decay to
      C(4)H(7)Cl + CO via transient hydrogen bonded C(4)H(7)(delta)(+)...Cl(delta-)
      complexes which possess significant ion pair character, even in the gas phase or
      in nonpolar solvents. In contrast to benzyloxychlorocarbene, no free radicals are
      formed upon generation or photolysis of 6 or 10 in Ar matrixes, although acid
      chlorides (the recombination products of these radical pairs) are observed. The
      IR spectra obtained in these experiments show the presence of several conformers
      of the two C(4)H(7)OC(..)Cl.

PMID- 15238005
TI  - Transparent conducting oxides: texture and microstructure effects on charge
      carrier mobility in MOCVD-derived CdO thin films grown with a thermally stable,
      low-melting precursor.
AB  - A series of low-melting, thermally stable cadmium metal-organic chemical vapor
      deposition (MOCVD) precursors have been synthesized, structurally and
      spectroscopically characterized, and implemented in growth of highly conductive
      and transparent CdO thin films. One member of the series, bis(1,1,1,5,5,5
      hexafluoro-2,4-pentanedionato)(N,N-diethyl-N',N'-dimethyl
      ethylenediamine)cadmium(II), Cd(hfa)(2)()(N,N-DE-N',N'-DMEDA), represents a
      particularly significant improvement over previously available Cd precursors,
      owing to the low melting point and robust thermal stability. High-quality CdO
      films were grown by MOCVD on glass and single-crystal MgO(100) between 300 and
      412 degrees C. Film growth parameters and substrate surface have large effects on
      microstructure and electron carrier transport properties. Enhanced mobilities
      observed for highly biaxially textured films grown on MgO(100) vs glass are
      attributed, on the basis of DC charge transport and microstructure analysis, to a
      reduction in neutral impurity scattering and/or to a more densely packed grain
      microstructure. Although single-grained films grown on MgO(100) exhibit greater
      mobilities than analogues with discrete approximately 100 nm grains and similar
      texture, this effect is attributed, on the basis of charge transport and Hall
      effect measurements as well as optical reflectivity analysis, to differences in
      carrier concentration rather than to reduced grain boundary scattering.
      Unprecedented conductivities and mobilities as high as 11,000 S/cm and 307
      cm(2)/V.s, respectively, are obtained for epitaxial single-grained films (X-ray
      diffraction parameters: fwhm(omega) = 0.30 degrees, fwhm(phi) = 0.27 degrees )
      grown in situ on MgO(100) at a relatively low temperature (400 degrees C).

PMID- 15238006
TI  - "Polysiloxane-Pd" nanocomposites as recyclable chemoselective hydrogenation
      catalysts.
AB  - Polysiloxane-encapsulated "Pd"-nanoclusters were generated by reduction of
      Pd(OAc)(2) with polymethylhydrosiloxane, which functions as a reducing agent as
      well as a capping material for production and stabilization of catalytically
      active "Pd"-nanoparticles. Chemoselective hydrogenation of functional conjugated
      alkenes was achieved by in-situ- or ex-situ-generated polysiloxane-stabilized
      "Pd"-nanoclusters under mild reaction conditions in high yields. Electron
      microscopy, UV-vis, and NMR studies of the reaction mixture during the catalytic
      transformation were performed and, in conjunction with catalyst poisoning
      experiments, demonstrated unequivocally the role of polysiloxane-encapsulated
      "Pd"-nanoclusters as the real catalytic species. The recyclability of the "Pd"
      nanoclusters was established by reusing the solid left after the reaction.

PMID- 15238007
TI  - Cytochrome P450CAM enzymatic catalysis cycle: a quantum mechanics/molecular
      mechanics study.
AB  - The catalytic pathway of cytochrome P450cam is studied by means of a hybrid
      quantum mechanics/molecular mechanics method. Our results reveal an active role
      of the enzyme in the different catalytic steps. The protein initially controls
      the energy gap between the high- and low-spin states in the substrate binding
      process, allowing thermodynamic reduction by putidaredoxin reductase and
      molecular oxygen addition. A second electron reduction activates the delivery of
      protons to the active site through a selective interaction of Thr252 and the
      distal oxygen causing the O--O cleavage. Finally, the protein environment
      catalyzes the substrate hydrogen atom abstraction step with a remarkably low free
      energy barrier ( approximately 8 kcal/mol). Our results are consistent with the
      effect of mutations on the enzymatic efficacy and provide a satisfactory
      explanation for the experimental failure to trap the proposed catalytically
      competent species, a ferryl Fe(IV) heme.

PMID- 15238008
TI  - Mechanism, selectivity promotion, and new ultraselective pathways in Ag-catalyzed
      heterogeneous epoxidation.
AB  - The selective oxidation of styrene on clean and modified Ag(100) surfaces has
      been studied by synchrotron fast XPS and temperature-programmed reaction
      spectroscopy. By following the time dependence of surface species, it is
      unequivocally demonstrated that the necessary and sufficient conditions for
      epoxide formation are oxygen adatoms and pi-adsorbed alkene molecules. Increased
      oxygen coverage and coadsorbed Cs have pronounced and opposite effects on
      epoxidation selectivity, consistent with the view that the valence charge density
      on O(a) is pivotal in determining this property. Submonolayer quantities of Cs
      nitrate generated in situ open a new, low-temperature ultraselective, epoxidation
      pathway thought to involve direct oxygen transfer from the oxyanion to the
      alkene.

PMID- 15238009
TI  - Structural mining: self-consistent design on flexible protein-peptide docking and
      transferable binding affinity potential.
AB  - A flexible protein-peptide docking method has been designed to consider not only
      ligand flexibility but also the flexibility of the protein. The method is based
      on a Monte Carlo annealing process. Simulations with a distance root-mean-square
      (dRMS) virtual energy function revealed that the flexibility of protein side
      chains was as important as ligand flexibility for successful protein-peptide
      docking. On the basis of mean field theory, a transferable potential was designed
      to evaluate distance-dependent protein-ligand interactions and atomic solvation
      energies. The potential parameters were developed using a self-consistent process
      based on only 10 known complex structures. The effectiveness of each intermediate
      potential was judged on the basis of a Z score, approximating the gap between the
      energy of the native complex and the average energy of a decoy set. The Z score
      was determined using experimentally determined native structures and decoys
      generated by docking with the intermediate potentials. Using 6600 generated
      decoys and the Z score optimization criterion proposed in this work, the
      developed potential yielded an acceptable correlation of R(2) = 0.77, with
      binding free energies determined for known MHC I complexes (Class I Major
      Histocompatibility protein HLA-A(*)0201) which were not present in the training
      set. Test docking on 25 complexes further revealed a significant correlation
      between energy and dRMS, important for identifying native-like conformations. The
      near-native structures always belonged to one of the conformational classes with
      lower predicted binding energy. The lowest energy docked conformations are
      generally associated with near-native conformations, less than 3.0 Angstrom dRMS
      (and in many cases less than 1.0 Angstrom) from the experimentally determined
      structures.

PMID- 15238011
TI  - Fast intramolecular charge transfer with a planar rigidized electron
      donor/acceptor molecule.
AB  - The planar rigidized molecule fluorazene (FPP) undergoes fast reversible
      intramolecular charge transfer (ICT) in the excited state, with a reaction time
      of 12 ps in the polar solvent ethyl cyanide at -45 degrees C. The ICT state of
      FPP has a dipole moment mu(e)(ICT) of 13 D, much larger than that of the locally
      excited state LE (1 D). The ICT behavior of FPP is similar to that of its
      flexible counterpart N-phenylpyrrole (PP), for which mu(e)(ICT) = 12 D. These
      results show that intramolecular charge transfer to a planar ICT state can occur
      efficiently. In designing ICT systems capable of rapid switching, it is therefore
      important to realize that large amplitude motions such as those necessary for the
      formation of a twisted intramolecular charge transfer (TICT) state are not
      required.

PMID- 15238010
TI  - Ab initio study of (13)C(alpha) chemical shift anisotropy tensors in peptides.
AB  - This study reports magnitudes and the orientation of the (13)C(alpha) chemical
      shift anisotropy (CSA) tensors of peptides obtained using quantum chemical
      calculations. The dependency of the CSA tensor parameters on the energy
      optimization of hydrogen atom positions and hydrogen bonding effects and the use
      of zwitterionic peptides in the calculations are examined. Our results indicate
      that the energy optimization of the hydrogen atom positions in crystal structures
      is necessary to obtain accurate CSA tensors. The inclusion of intermolecular
      effects such as hydrogen bonding in the calculations provided better agreement
      between the calculated and experimental values; however, the use of zwitterionic
      peptides in calculations, with or without the inclusion of hydrogen bonding, did
      not improve the results. In addition, our calculated values are in good agreement
      with tensor values obtained from solid-state NMR experiments on glycine
      containing tripeptides. In the case of peptides containing an aromatic residue,
      calculations on an isolated peptide yielded more accurate isotropic shift values
      than the calculations on extended structures of the peptide. The calculations
      also suggested that the presence of an aromatic ring in the extended crystal
      peptide structure influences the magnitude of the delta(22) which the present
      level of ab initio calculations are unable to reproduce.

PMID- 15238012
TI  - Two-dimensional supramolecular organization of copper octaethylporphyrin and
      cobalt phthalocyanine on Au(111): molecular assembly control at an
      electrochemical interface.
AB  - Mixed adlayers of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine copper(II)
      (CuOEP) and cobalt(II) phthalocyanine (CoPc) were prepared by immersing Au(111)
      substrate in a benzene solution containing CuOEP and CoPc molecules, and they
      were investigated in 0.1 M HClO(4) by cyclic voltammetry (CV) and in-situ
      scanning tunneling microscopy (STM). The composition of the mixed adlayer
      consisting of CuOEP and CoPc molecules was found to vary depending on the
      immersion time. CoPc molecules displaced CuOEP molecules during the modification
      process with increasing immersion time, and the CuOEP molecules were completely
      replaced with CoPc molecules in the mixed solution after a long modification
      time. The two-component adlayer consisting of CuOEP and CoPc, which has a
      structure with the constituent molecules arranged alternately, was found to form
      either a p(9 x 3(square root)7R - 40.9 degrees) or a p(9 x 3(square root)7R -
      19.1 degrees) structure, each involving two molecules on the Au(111) surface. The
      surface mobility and the molecular reorganization of CuOEP and CoPc were
      accelerated by modulation of the electrode potential. Different surface
      structures were produced at different electrode potentials, and hence potential
      modulation should allow a precisely controllable phase separation to take place
      in aqueous HClO(4).

PMID- 15238013
TI  - Correlation between crystal structure and mobility in organic field-effect
      transistors based on single crystals of tetrathiafulvalene derivatives.
AB  - Recently, it was reported that crystals of the organic material dithiophene
      tetrathiafulvalene (DT-TTF) have a high field-effect charge carrier mobility of
      1.4 cm(2)/(V x s). These crystals were formed by a simple drop-casting method,
      making this material interesting to investigate for possible applications in low
      cost electronics. Here, organic single-crystal field-effect transistors based on
      materials related to DT-TTF are presented and a clear correlation between the
      crystal structure and the electrical characteristics is observed. The observed
      relationship between the mobilities in the different crystal structures is
      strongly corroborated by calculations of both the molecular reorganization
      energies and the maximum intermolecular transfer integrals. The most suitable
      materials described here exhibit mobilities that are among the highest reported
      for organic field-effect transistors and that are the highest reported for
      solution-processed materials.

PMID- 15238014
TI  - A molecularly imprinted polymer-based synthetic transaminase.
AB  - The design, synthesis, and evaluation of a molecularly imprinted polymer
      transaminase mimic is described. Methacrylic acid-ethylene glycol dimethacrylate
      copolymers were synthesized using, as a template, a transition state analogue
      (TSA) for the reaction of phenylpyruvic acid and pyridoxamine to yield
      phenylalanine and pyridoxal. Polymer suitability was established on the basis of
      (1)H NMR studies of template-functional monomer interactions. Polymer recognition
      characteristics were examined in a series of HPLC studies using the polymers as
      chromatographic stationary phases. Selectivity for the TSA, relative to
      substrates and products, was observed in both aqueous and nonpolar media. In the
      latter case (chloroform/AcOH, 96:4), an enantioseparation factor (alpha) of 2.1
      was obtained, and frontal chromatographic studies revealed the presence of 11.9
      +/- 0.2 micromol g(-1) (dry weight) of enantioselective sites. Polymers imprinted
      with the l-form of the oxazine-based TSA induced a 15-fold enhancement of the
      apparent reaction rate (app. V(max) 2.5 x 10(-7) mol s(-1); app. K(m) 8.2 x 10(
      3) M) and enantioselective production of phenylalanine (32 +/- 4% ee) for
      reactions conducted in an aqueous buffer system. Substrate selectivity was
      evident, and a turnover number (k(cat)) of 0.1 s(-)(1) was determined. This is
      the first example of the catalysis of sigmatropic shifts in aqueous media by
      molecularly imprinted polymers.

PMID- 15238015
TI  - Incorporation of fullerene derivatives into smectite clays: a new family of
      organic-inorganic nanocomposites.
AB  - Three fulleropyrrolidine derivatives, characterized by the presence of positive
      charges, were introduced in the interlayer space of montmorillonite. The
      composites were characterized by powder X-ray diffraction and differential
      thermal and thermogravimetric (DTA-TGA) analysis, in conjunction with FTIR, UV
      Vis, Raman, and (57)Fe-Mossbauer spectroscopies. Organophilic derivatives were
      intercalated into organically modified clays, while water-soluble
      fulleropyrrolidines were introduced into the clay galleries through ion exchange.
      The experiments, complemented by computer simulations, show that not all the clay
      clay platelets are intercalated by the fullerene derivatives and that a sizable
      amount of charge transfer takes place between the host and the guests.

PMID- 15238016
TI  - Highly efficient transfer of chirality from macrocyclic conformation in the
      tandem oxy-Cope/Claisen/ene reaction.
AB  - We report three highly stereoselective pericyclic reactions occurring in cascade
      leading to the synthesis of Decalins skeletons possessing two contiguous
      quaternary centers. The tandem reaction is triggered by an oxy-Cope rearrangement
      to create in situ a 10-membered ring enol ether macrocyle 6, which immediately
      rearranges via a Claisen [3,3] shift to the corresponding E-cyclodec-6-en-1-one
      7. The latter spontaneously cyclizes via a transannular ene reaction to produce
      Decalin 5. Analysis of the mechanism with respect to the origin of the high
      diastereoselectivity of the tandem oxy-Cope/Claisen/ene reaction is presented.

PMID- 15238017
TI  - Structure and reactivity of Ru nanoparticles supported on modified graphite
      surfaces: a study of the model catalysts for ammonia synthesis.
AB  - Supported ruthenium metal catalysts have higher activity than traditional iron
      based catalysts used industrially for ammonia synthesis. A study of a model Ru/C
      catalyst was carried out to advance the understanding of structure and reactivity
      correlations in this structure-sensitive reaction where dinitrogen dissociation
      is the rate-limiting step. Ru particles were grown by chemical vapor deposition
      (CVD) via a Ru(3)(CO)(12) precursor on a highly oriented pyrolytic graphite
      (HOPG) surface modified with one-atomic-layer-deep holes mimicking activated
      carbon support. Scanning tunneling microscopy (STM) has been used to investigate
      the growth, structure, and morphology of the Ru particles. Thermal desorption of
      dissociatively adsorbed nitrogen has been used to evaluate the reactivity of the
      Ru/HOPG model catalysts. Two different Ru particle structures with different
      reactivities to N(2) dissociation have been identified. The initial sticking
      coefficient for N(2) dissociative adsorption on the Ru/HOPG model catalysts is
      approximately 10(-6), 4 orders larger compared to that of Ru single-crystal
      surfaces.

PMID- 15238018
TI  - Photoelectron spectroscopy of isolated multiply negatively charged
      oligonucleotides.
AB  - Ultraviolet photoelectron spectroscopy in an ion beam was used to investigate the
      electronic properties of isolated DNA oligonucleotides [dA(5)-4H](4-) and [dT(5)
      4H](4-), carrying four excess negative charges. We find the fourth adiabatic
      electron affinity to be slightly negative for [dA(5)-4H](4-), while it is
      positive for [dT(5)-4H](4-). This implies a significant influence of the base
      composition on energetics, which is in turn relevant for analytic applications
      and also for charge transport properties.

PMID- 15238020
TI  - Verbalizing facial memory: criterion effects in verbal overshadowing.
AB  - This article investigated the role of the recognition criterion in the verbal
      overshadowing effect (VOE). In 3 experiments, people witnessed an event, verbally
      described a perpetrator, and then attempted identification. The authors found in
      Experiment 1, which included a "not present" response option and both perpetrator
      present (PP) and perpetrator-absent (PA) lineups, an increased reluctance to
      identify a person from both lineup types after verbalization. Experiment 2
      incorporated a forced-choice procedure, and the authors found no effect of
      verbalization on identification performance. Experiment 3 replicated the
      essential aspects of these results. Consequently, the VOE may reflect a change in
      recognition criterion rather than a changed processing style or alteration of the
      underlying memory trace. This conclusion was confirmed by computational modeling
      of the data.

PMID- 15238021
TI  - A multinomial model of event-based prospective memory.
AB  - Prospective memory is remembering to perform an action in the future. The authors
      introduce the 1st formal model of event-based prospective memory, namely, a
      multinomial model that includes 2 separate parameters related to prospective
      memory processes. The 1st measures preparatory attentional processes, and the 2nd
      measures retrospective memory processes. The model was validated in 4
      experiments. Manipulations of instructions to place importance on either the
      prospective memory task or the background task (Experiments 1 and 2) and
      manipulations of distinctiveness of prospective memory targets (Experiment 2) had
      expected effects on model parameters, as did a manipulation of the difficulty of
      prospective memory target encoding (Experiments 3 and 4). An alternative model
      was also evaluated.

PMID- 15238022
TI  - Interactions between study task, study time, and the low-frequency hit rate
      advantage in recognition memory.
AB  - In studies of episodic recognition memory, low-frequency words (LF) have higher
      hit rates (HR) and lower false alarm rates (FAR) than do high-frequency words
      (HF), which is known as the mirror pattern. A few findings have suggested that
      requiring a task at study may reduce or eliminate the LF-HR advantage without
      altering the LF-FAR effect. Other studies have suggested that the size of the LF
      HR advantage interacts with study time. To explore such findings more thoroughly
      and relate them to theory, the authors conducted 5 experiments, varying study
      time and study task. The full mirror pattern was found only in 2 cases: the
      standard condition requiring study for a later memory test and a condition
      requiring a judgment about unusual letters. The authors explain their findings in
      terms of the encoding of distinctive features and discuss the implications for
      current theories of recognition memory and the word frequency effect.

PMID- 15238023
TI  - Why distinctive information reduces false memories: evidence for both
      impoverished relational-encoding and distinctiveness heuristic accounts.
AB  - Two accounts explain why studying pictures reduces false memories within the
      Deese-Roediger-McDermott paradigm (J. Deese, 1959; H. L. Roediger & K. B.
      McDermott, 1995). The impoverished relational-encoding account suggests that
      studying pictures interferes with the encoding of relational information, which
      is the primary basis for false memories in this paradigm. Alternatively, the
      distinctiveness heuristic assumes that critical lures are actively withheld by
      the use of a retrieval strategy. When participants were given inclusion recall
      instructions to report studied items as well as related items, they still
      reported critical lures less often after picture encoding than they did after
      word encoding. As the impoverished relational-encoding account suggests, critical
      lures appear less likely to come to mind after picture encoding than they do
      after word encoding. However, the results from a postrecall recognition test
      provide evidence in favor of the distinctiveness heuristic.

PMID- 15238024
TI  - Detrimental influence of contextual change on spacing effects in free recall.
AB  - Two experiments were conducted to determine the mechanism underlying the spacing
      effect in free-recall tasks. Participants were required to study a list
      containing once-presented words as well as massed and spaced repetitions. In both
      experiments, presentation background at repetition was manipulated. The results
      of Experiment 1 demonstrated that free recall was higher for massed items
      repeated in a different context than for massed items repeated in the same
      context, whereas free recall for spaced items was higher when repeated in the
      same context. Furthermore, a spacing effect was shown for words repeated in the
      same context, whereas an attenuated spacing effect was revealed for words
      repeated in a different context. These findings were replicated in Experiment 2
      under a different presentation background manipulation. Both experiments seem to
      be most consistent with a model that combines the contextual variability and the
      study-phase retrieval mechanism to account for the spacing effect in free-recall
      tasks.

PMID- 15238025
TI  - Functional equivalence of spatial representations derived from vision and
      language: evidence from allocentric judgments.
AB  - Past research (e.g., J. M. Loomis, Y. Lippa, R. L. Klatzky, & R. G. Golledge,
      2002) has indicated that spatial representations derived from spatial language
      can function equivalently to those derived from perception. The authors tested
      functional equivalence for reporting spatial relations that were not explicitly
      stated during learning. Participants learned a spatial layout by visual
      perception or spatial language and then made allocentric direction and distance
      judgments. Experiments 1 and 2 indicated allocentric relations could be
      accurately reported in all modalities, but visually perceived layouts, tested
      with or without vision, produced faster and less variable directional responses
      than language. In Experiment 3, when participants were forced to create a spatial
      image during learning (by spatially updating during a backward translation),
      functional equivalence of spatial language and visual perception was demonstrated
      by patterns of latency, systematic error, and variability.

PMID- 15238026
TI  - Effects of orthographic and phonological word length on memory for lists shown at
      RSVP and STM rates.
AB  - This article reports 3 experiments in which effects of orthographic and
      phonological word length on memory were examined for short lists shown at rapid
      serial visual presentation (RSVP) and short-term memory (STM) rates. Only visual
      orthographic length reduced RSVP serial recall, whereas both orthographic and
      phonological length lowered recall for STM lists in Experiment 1. Word-length
      effects may arise from output processes or from the temporal duration of output
      in recall. In 2 further experiments, output demands were reduced through the use
      of a recognition test. Recognition accuracy was impaired only by orthographic
      length for RSVP lists and by phonological length for STM lists in both
      experiments. The results demonstrate 2 item length effects not simply
      attributable to increased output time in recall, and implications for theories of
      STM are considered.

PMID- 15238027
TI  - Cognitive operations in the generation effect on a recall test: role of aging and
      divided attention.
AB  - Generation effect (generated words are better memorized than read words) of
      anagrams, rhymes, and associates of target words was examined in young, elderly,
      and very old subjects. Experiments 1 and 2 showed that only young subjects
      benefit from the generation effect in a free-recall test when the rule is of a
      phonological nature. Experiments 3, 4, and 5 showed that the generation effect of
      rhymes was due to a resources-dependent self-initiated process. Experiments 4 and
      5 showed that in a divided-attention situation, generation effect of rhymes is
      not significant in young subjects, but that the generation effect of semantic
      associates remains significant for both groups (Experiment 5). The results are
      discussed within the environmental support framework and the transfer-appropriate
      processing framework.

PMID- 15238028
TI  - Generation and memory for contextual detail.
AB  - Generation enhances item memory but may not enhance other aspects of memory. In
      12 experiments, the author investigated the effect of generation on context
      memory, motivated in part by the hypothesis that generation produces a trade-off
      in encoding item and contextual information. Participants generated some study
      words (e.g., hot-c__) and read others (e.g., hot-cold). Generation consistently
      enhanced item memory but did not enhance context memory. More specifically,
      generation disrupted context memory for the color of the target word but did not
      affect context memory for location, background color, and cue-word color. The
      specificity of the negative generation effect in context memory argues against a
      general item-context trade-off. A processing account of generation meets greater
      success. In addition, the results provide no evidence that generation enhances
      recollection of contextual details.

PMID- 15238029
TI  - The advantage of timely intervention.
AB  - Can people learn causal structure more effectively through intervention rather
      than observation? Four studies used a trial-based learning paradigm in which
      participants obtained probabilistic data about a causal chain through either
      observation or intervention and then selected the causal model most likely to
      have generated the data. Experiment 1 demonstrated that interveners made more
      correct model choices than did observers, and Experiments 2 and 3 ruled out
      explanations for this advantage in terms of informational differences between the
      2 conditions. Experiment 4 tested the hypothesis that the advantage was driven by
      a temporal signal; interveners may exploit the cue that their interventions are
      the most likely causes of any subsequent changes. Results supported this temporal
      cue hypothesis.

PMID- 15238030
TI  - Temporal references and temporal relations in sentence comprehension.
AB  - The author investigated the interpretation of temporal references during
      comprehension of sentences containing a main and subordinate clause. Experiments
      1 and 2 examined state and event subordinate clauses, respectively, and showed
      that subordinate temporal references overlapping with or close to the time of the
      main clause event were read faster than nonoverlapping distant references.
      Experiment 3 examined temporal references in nonsubordinate main clauses and
      confirmed that temporal relations between main and subordinate clauses were
      established on-line in the previous experiments. Experiment 4 independently
      manipulated temporal overlap and distance and suggested that event and state
      clauses are processed according to distinct temporal parameters. The results are
      explained by the contingency relations that events and states establish with
      other discourse events.

PMID- 15238031
TI  - The perception of integrality: remembering through the validation of expectation.
AB  - Five experiments investigated the role of sentence context in influencing
      recognition decisions. Sentence stems were presented only in the study phase,
      only in the test phase, or in both; in addition, the coherence of the sentences
      was varied, such that terminal words were highly constrained by, merely
      consistent with, or actually incongruous with their stems. These stimulus
      combinations produced 4 unique patterns of response. These patterns are difficult
      to explain through encoding and retrieval alone; they seem also to require an
      understanding of the principles by which people react subjectively to their own
      processing. The results are discussed in terms of the differential effects of
      definite expectations developed in past experiences versus indefinite
      expectations developed in the moment of remembering.

PMID- 15238032
TI  - Contributions of metaknowledge to retrieval of natural categories in semantic
      memory.
AB  - Retrieving the answer to a general knowledge question has been shown to involve
      two metacognitive processes--a feeling-of-knowing that initiates the search of
      long-term memory and a willingness to continue searching until an answer can be
      confidently stated. To extend this model, college students were asked to retrieve
      as many members of 2 natural categories as they could in 1 min. Examination of
      the points at which they switched categories revealed that they searched longer
      in categories of higher potency, and they switched earlier when the other
      category was of higher potency. They also searched the first category longer when
      they were allowed to switch only once during a trial rather than as often as they
      wished. It was concluded that feeling-of-knowing maintained search of a category
      and also contributed to the willingness to continue searching, and the constraint
      on switching impacted the willingness to continue.

PMID- 15238033
TI  - The role of familiarity in episodic memory and metamemory for music.
AB  - Participants heard music snippets of varying melodic and instrumental familiarity
      paired with animal-name titles. They then recalled the target when given either
      the melody or the title as a cue, or they gave name feeling-of-knowing (FOK)
      ratings. In general, recall for titles was better than it was for melodies, and
      recall was enhanced with increasing melodic familiarity of both the cues and the
      targets. Accuracy of FOK ratings, but not magnitude, also increased with
      increasing familiarity. Although similar ratings were given after melody and
      title cues, accuracy was better with title cues. Finally, knowledge of the real
      titles of the familiar music enhanced recall but had, by and large, no effect on
      the FOK ratings.

PMID- 15238034
TI  - On the role of recognition in decision making.
AB  - In 2 experiments, the authors sought to distinguish between the claim that
      recognition of an object is treated simply as a cue among others for the purposes
      of decision making in a cue-learning task from the claim that recognition is
      attributed a special status with fundamental, noncompensatory properties. Results
      of both experiments supported the former interpretation. When recognition had a
      high predictive validity, it was relied on (solely) by the majority of
      participants; however, when other cues in the environment had higher validity,
      recognition was ignored, and these other cues were used. The results provide
      insight into when, where, and why recognition is used in decision making and also
      question the elevated status assigned to recognition in some frameworks (e.g., D.
      G. Goldstein & G. Gigerenzer, 2002).

PMID- 15238035
TI  - Exemplars, prototypes, and the flexibility of classification models.
AB  - J. P. Minda and J. D. Smith (2001) showed that a prototype model outperforms an
      exemplar model, especially in larger categories or categories that contained more
      complex stimuli. R. M. Nosofsky and S. R. Zaki (2002) showed that an exemplar
      model with a response-scaling mechanism outperforms a prototype model. The
      authors of the current study investigated whether excessive model flexibility
      could explain these results. Using cross-validation, the authors demonstrated
      that both the prototype model and the exemplar model with a response-scaling
      mechanism suffered from overfilling in the linearly separable category structure.
      The results illustrate the need to make sure that the best-fitting model is not
      chasing error variance instead of variance attributed to the cognitive process it
      is supposed to model.

PMID- 15238036
TI  - Once in contact, always in contact: contagious essence and conceptions of
      purification in American and Hindu Indian children.
AB  - Cultural and age differences in responses to contamination and conceptions of
      purification were examined in Hindu Indian (N = 125) and American (N = 106) 4- to
      5-year-olds and 8-year-olds, who were provided with stories of juice contaminated
      by contact with a cockroach, a human hair, and a stranger (via sipping). Children
      who rejected the juice as being fit to drink were probed to determine whether
      their rejection was based on material essence (reduced by boiling), association
      (reduced by color change), or spiritual essence (reduced by sipping by the
      mother). A majority of 4- to 5-year-olds showed some form of contamination
      response, as did the great majority of 8-year-olds. Younger children's judgments
      were often based on spiritual essence or association, whereas material essence
      was more important for the older children, particularly Americans. However, for
      many children in both cultures, no purifiers were effective. In keeping with
      Hindu culture, the Indian children responded significantly more strongly to
      stranger or cockroach contamination and, with increasing age, viewed
      contamination as more impervious to any kind of purification.

PMID- 15238037
TI  - Maternal regulation of infant reactivity from 2 to 6 months.
AB  - Previous research has investigated the effect of maternal soothing behaviors on
      reducing infant reactivity but not the differential effects of specific maternal
      behaviors on infant stress responses. The present study investigated maternal
      regulation of 2- and 6-month-olds' responses to an inoculation and found a
      significant decline with age in both the intensity and duration of infants'
      crying. Maternal affection and touching decreased from 2 to 6 months, whereas
      maternal vocalizing and distraction behaviors increased. At both ages, the
      combination of maternal holding/rocking and vocalizing was associated with
      decreases in all levels of infant reactivity. Neither strategy alone, however,
      was found to be effective. Feeding/ pacifying behaviors were effective only when
      initial distress was at a low or moderate level, which suggests that the
      effectiveness of maternal regulatory behaviors may depend on the intensity of
      infants' crying.

PMID- 15238038
TI  - A randomized study of neighborhood effects on low-income children's educational
      outcomes.
AB  - Experimental data from the Moving to Opportunity for Fair Housing Demonstration
      were used to examine (a) if moving from high- to low-poverty neighborhoods (via
      randomization) was associated with low-income minority children's achievement,
      grade retention, and suspensions/expulsions; (b) if moving minimized gender
      differences in these outcomes; and (c) potential mediators of observed program
      effects. Data on school-age children (mean age = 11.79 years, SD = 3.26) were
      obtained from standardized assessments and parent and adolescent interviews
      during the New York City site's 3-year follow-up evaluation (N = 588). Moving to
      low-poverty neighborhoods had positive effects on 11-18-year-old boys'
      achievement scores compared with those of their peers in high-poverty
      neighborhoods. These male adolescents' scores were comparable to females' scores,
      whereas male adolescents in high-poverty neighborhoods scored 10 points lower
      than female peers. Homework time and school safety partially accounted for
      program effects. From a policy perspective, the program benefited disadvantaged
      male adolescents at high risk for dropping out of school.

PMID- 15238039
TI  - Through Colombian lenses: ethnographic and conventional analyses of maternal care
      and their associations with secure base behavior.
AB  - According to attachment theory, the quality of care plays a key role in the
      organization of infants' secure base behavior across contexts and cultures. Yet
      information about attachment relationships in a variety of cultures is scarce,
      and questions remain as to whether Ainsworth's conceptualization of early care
      quality (sensitivity; M. D. S. Ainsworth, M. C. Blehar, E. Waters, & S. Wall,
      1978) is appropriate for characterizing caregiving behavior in different groups
      and whether culturally specific descriptions of early care are related to
      conventional measures of maternal sensitivity and to infants' security. In this
      naturalistic study of mother-infant interactions in Colombia, scores on different
      domains of maternal care were obtained through ethnographic methodology, and
      conventional Q-sort scores for maternal and infant behavior were obtained.
      Findings are discussed in terms of the cross-cultural generality of the
      sensitivity construct and the sensitivity-security link and of the relevance of
      naturalistic open-ended studies in different contexts.

PMID- 15238040
TI  - Attachment at early school age and developmental risk: examining family contexts
      and behavior problems of controlling-caregiving, controlling-punitive, and
      behaviorally disorganized children.
AB  - Preschool to school-age trajectories of 242 children, including 37 with insecure
      disorganized and 66 with insecure-organized attachment patterns, were examined.
      Child attachment and stressful life events (the latter retrospectively) were
      measured at ages 5-7, and mother-child interactive quality, parenting stress,
      marital satisfaction, and teacher-reported behavior problems were evaluated
      concurrently and 2 years earlier. Results indicated that all three disorganized
      subgroups had poorer mother-child interactive patterns and more difficult family
      climates than secure or insecure-organized children. The controlling-punitive
      group showed significant increases in maternal reports of child-related stress
      between preschool and school age. The controlling-caregiving group showed greater
      likelihood of loss of a close family member, and mothers of the insecure-other
      group reported lower marital satisfaction and greater likelihood of their own or
      a spouse's hospitalization. Controlling-punitive children had higher
      externalizing scores, and controlling-caregiving children higher internalizing
      scores, than secure children.

PMID- 15238041
TI  - The effects of family, school, and classroom ecologies on changes in children's
      social competence and emotional and behavioral problems in first grade.
AB  - This study tested the independent and interactive influences of classroom
      (concentrations of peer prosocial behaviors and victimization), family (household
      moves, mothers' education), and school (proportion of students receiving income
      assistance) ecologies on changes in children's social competence (e.g.,
      interpersonal skills, leadership abilities), emotional problems (e.g., anxious,
      withdrawn behaviors), and behavioral problems (e.g., disruptiveness,
      aggressiveness) in first grade. Higher classroom concentrations of prosocial
      behaviors and victimization predicted increases in social competence, and greater
      school disadvantage predicted decreases. Multiple household moves and greater
      school disadvantage predicted increases in behavioral problems. Multiple
      household moves and low levels of mothers' education predicted increases in
      emotional problems for children in classrooms with few prosocial behaviors.
      Greater school disadvantage predicted increases in emotional problems for
      children in classrooms with low prosocial behaviors and high victimization.
      Policy implications of these findings are considered.

PMID- 15238042
TI  - Visual search across the life span.
AB  - Gains and losses in visual search were studied across the life span in a
      representative sample of 298 individuals from 6 to 89 years of age. Participants
      searched for single-feature and conjunction targets of high or low eccentricity.
      Search was substantially slowed early and late in life, age gradients were more
      pronounced in conjunction than in feature search, and all age groups were
      uniformly affected by eccentricity manipulations. However, developmental and
      aging trends were distinctly asymmetrical: Children's performance was
      particularly affected by the mere presence of distractors; whereas in late life,
      performance was particularly impaired on target-absent trials and with increasing
      numbers of distractors. The implications for life span theories of cognitive and
      attentional development and for cognitive-speed and inhibitory-control accounts
      are discussed.

PMID- 15238043
TI  - Theories of conditional reasoning: a developmental examination of competing
      hypotheses.
AB  - Children and adolescents were presented with problems that contained deontic
      (i.e., if action p is taken, then precondition q must be met) or causal (i.e., if
      event p occurs, then event q will transpire) conditionals and that varied in the
      ease with which alternative antecedents could be activated. Results showed that
      inferences were linked to the availability of alternative antecedents and the
      generation of "disabling" conditions (claims that the conditionals were false
      under specific circumstances). Age-related developments were found only on
      problems involving indeterminate inferences. Correlations among inferences
      differed for children and adolescents. The findings provide stronger support for
      domain-general theories than for domain-specific theories of reasoning and
      suggest, under some conditions, age-related changes in the roles of implicit and
      explicit processing.

PMID- 15238044
TI  - Does gender identity influence children's psychological well-being?
AB  - This study examined influences of gender identity on change in preadolescents'
      adjustment over time. In each of two successive years, three measures of gender
      identity (felt gender typicality, contentment with gender assignment, and felt
      pressure for gender conformity) and four measures of adjustment (self-esteem,
      internalizing symptoms, externalizing symptoms, and acceptance by peers) were
      collected. Low gender typicality, low gender contentedness, and high felt
      pressure all foreshadowed deterioration on one or more indexes of adjustment. The
      combination of low gender typicality with high felt pressure was especially
      conducive to internalizing problems, underscoring the importance of the cognitive
      organization of the gender identity variables. The advantages of a
      multidimensional perspective on gender identity are discussed.

PMID- 15238045
TI  - Context-specific freezing and associated physiological reactivity as a
      dysregulated fear response.
AB  - The putative association between fear-related behaviors and peripheral
      sympathetic and neuroendocrine reactivity has not been replicated consistently.
      This inconsistency was addressed in a reexamination of the characterization of
      children with extreme fearful reactions by focusing on the match between distress
      behaviors and the eliciting context. Eighty 24-month-old children were observed
      in 4 mildly threatening contexts, and the relations among different measures of
      fear-related behaviors, reactive and basal cortisol levels, and baseline cardiac
      measures of heart rate, respiratory sinus arrhythmia, and preejection period
      (PEP) were examined. The hypothesis that only behaviors under the less
      threatening context would be associated with higher cortisol and sympathetic
      cardiac activity was confirmed; only task-specific freezing behavior predicted
      higher reactive and basal cortisol levels and resting PEP measured 1 week later.
      Implications for the conceptualization of dysregulated fear behaviors in the
      classification of extremely fearful children are discussed.

PMID- 15238046
TI  - Learning as a task or a virtue: U.S. And Chinese preschoolers explain learning.
AB  - The purpose of this study was to examine cultural influences on conceptual
      orientations of learning in U.S. and Chinese preschoolers. A sample of 188
      preschoolers 4-6 years of age provided free-narrative responses to 2 story
      beginnings about the learning behavior of 2 protagonists, 1 who worked hard and 1
      who gave up. Results showed that despite some differences in the younger age
      groups, children from both cultures valued learning similarly at age 6. However,
      important cultural differences emerged in children's construals of the learning
      process. U.S. children showed a heightened awareness of the mind/task attributes
      of the learner, that is, ability, task attempting, and strategy use. By contrast,
      Chinese children perceived more the learner's dispositional qualities of
      diligence, persistence, and concentration. These trends increased as children's
      age increased. The U.S. findings are interpreted as reflecting the U.S. cultural
      emphasis on learning as a task, and the Chinese results, as reflecting the
      Chinese cultural focus on learning as a process of cultivating personal virtue.

PMID- 15238047
TI  - Object permanence after a 24-hr delay and leaving the locale of disappearance:
      the role of memory, space, and identity.
AB  - Fourteen-month-old infants saw an object hidden inside a container and were
      removed from the disappearance locale for 24 hr. Upon their return, they searched
      correctly for the hidden object, demonstrating object permanence and long-term
      memory. Control infants who saw no disappearance did not search. In Experiment 2,
      infants returned to see the container either in the same or a different room.
      Performance by room-change infants dropped to baseline levels, suggesting that
      infant search for hidden objects is guided by numerical identity. Infants seek
      the individual object that disappeared, which exists in its original location,
      not in a different room. A new behavior, identity-verifying search, was
      discovered and quantified. Implications are drawn for memory, spatial
      understanding, object permanence, and object identity.

PMID- 15238048
TI  - Reexamining the vocabulary spurt.
AB  - The authors asked whether there is evidence to support the existence of the
      vocabulary spurt, an increase in the rate of word learning that is thought to
      occur during the 2nd year of life. Using longitudinal data from 38 children, they
      modeled the rate of word learning with two functions, one with an inflection
      point (logistic), which would indicate a spurt, and one without an inflection
      point (quadratic). Comparing the fits of these two functions using likelihood
      ratios, they found that just 5 children had a better logistic fit, which
      indicated that these children underwent a spurt. The implications for theories of
      cognitive and language development are considered.

PMID- 15238049
TI  - Preschool competency in context: an investigation of the unique contribution of
      child competencies to early academic success.
AB  - The present concurrent study combined developmental and ecological considerations
      to examine the unique contribution of multiple preschool competencies to an
      indicator of early academic success. Participants included 195 Head Start
      children from 32 classrooms representative of a large, urban Head Start program.
      Dimensional (variable-centered) analyses revealed 3 distinct classroom competency
      dimensions (i.e., General Classroom Competencies, Specific Approaches to
      Learning, and Interpersonal Classroom Behavioral Problems). The first 2 of these
      dimensions were found to be uniquely associated with early academic success.
      Findings from typological (person-centered) analyses supported the dimensional
      findings. Typological analyses revealed 7 profiles of classroom competency
      distinguished by high scores on the dimensions of General Competencies and
      Approaches to Learning, and these profiles were found to relate differentially to
      the indicator of early academic success.

PMID- 15238050
TI  - Measuring college students' motives for playing drinking games.
AB  - Students may choose to play drinking games not only for reasons related to
      alcohol consumption but also because of incentives related to other aspects of
      play (competition, fun, interpersonal dominance, etc.). College students (120 men
      and 167 women) completed measures of motives for playing (based on T. J. Johnson,
      S. Hamilton, & V. L. Sheets, 1999) and consequences of playing drinking games.
      Exploratory principal-components analysis identified 8 reasons for playing. Men
      and women differed in their endorsement of the factors. Motives for play directly
      predicted consequences of play independently of alcohol consumption. Specific
      motives predicted specific types of consequences. In multiple regression
      analyses, Conformity motives were negatively related to consequences and may
      represent a form of protective motive.

PMID- 15238051
TI  - The gambling urge scale: development, confirmatory factor validation, and
      psychometric properties.
AB  - The urge to gamble is a physiological, psychological, or emotional motivational
      state, often associated with continued gambling. The authors developed and
      validated the 6-item Gambling Urge Questionnaire (GUS), which was based on the 8
      item Alcohol Urge Questionnaire (M. J. Bohn, D. D. Krahn, & B. A. Staehler,
      1995), using 968 community-based participants. Exploratory factor analysis using
      half of the sample indicated a 1-factor solution that accounted for 55.18% of the
      total variance. This was confirmed using confirmatory factor analysis with the
      other half of the sample. The GUS had a Cronbach's alpha coefficient of.81.
      Concurrent, predictive, and criterion-related validity of the GUS were good,
      suggesting that the GUS is a valid and reliable instrument for assessing gambling
      urges among nonclinical gamblers.

PMID- 15238052
TI  - The predictive validity of the university of rhode island change assessment
      questionnaire in a heroin-addicted polysubstance abuse sample.
AB  - The purpose of this investigation was to examine the predictive utility of the
      stages-of-change scales of the University of Rhode Island Change Assessment
      (URICA; E. A. McConnaughy, J. O. Prochaska, & W. F. Velicer, 1983) questionnaire
      in a heroin-addicted polysubstance-abusing treatment sample. Ninety-six
      participants completed the URICA at the beginning of a 29-week treatment period
      that required thrice-weekly urine drug screens. Multivariate multiple regression
      analysis indicated that after controlling for demographic variables, substance
      abuse severity, and treatment assignment, the stages-of- change scales added
      significant variance to the prediction of heroin- and cocaine-free urine samples.
      The Maintenance scale was positively related to cocaine-free urines and length in
      treatment. The implications of these findings for treatment and for measuring
      readiness among individuals using multiple substances while taking maintenance
      medications are discussed.

PMID- 15238053
TI  - To have but one true friend: implications for practice of research on alcohol use
      disorders and social network.
AB  - Although social networks play an integral role in the recognition and resolution
      of drinking problems, social network influences may be positive, negative, or
      mixed. The author reviewed empirical literature on positive and negative aspects
      of the structure of problem drinkers' social networks, the impact of the social
      network on problem recognition, social network predictors of treatment outcomes,
      treatments that involve the social network in treatment, and posttreatment
      changes in social network structure and functioning. Future directions for
      research and clinical implications of research findings are discussed.

PMID- 15238054
TI  - Role of parent support and peer support in adolescent substance use: a test of
      mediated effects.
AB  - This research tested comparative effects of parent and peer support on adolescent
      substance use (tobacco, alcohol, and marijuana) with data from 2 assessments of a
      multiethnic sample of 1,826 adolescents, mean age 12.3 years. Multiple regression
      analyses indicated that parental support was inversely related to substance use
      and that peer support was positively related to substance use, as a suppression
      effect. Structural modeling analyses indicated that effects of support were
      mediated through pathways involving good self-control, poor self-control, and
      risk-taking tendency; parent and peer support had different patterns of relations
      to these mediators. The mediators had pathways to substance use through positive
      and negative recent events and through peer affiliations. Effects for gender and
      ethnicity were also noted. Mechanisms of operation for parent and peer support
      are discussed.

PMID- 15238055
TI  - Binge drinking among Latino youth: role of acculturation-related variables.
AB  - This research examined the relationship between acculturation-related variables
      and binge drinking behavior among nationally representative samples of Mexican
      American, Cuban American, and Puerto Rican youth. It explored the relationship
      between length of residence in the United States, type of language spoken in the
      home (Spanish vs. English) and binge drinking in each of these subgroups. Results
      suggest that Latino youths with no prior history of alcohol consumption remain
      largely unaffected by these acculturation-related variables. Youth with a
      previous history of alcohol consumption experience greater likelihood of binge
      drinking as a function of the acculturation-related variables, but the
      relationships are complex.

PMID- 15238056
TI  - Sports betting: can gamblers beat randomness?
AB  - Although skills are not considered relevant in chance-governed activities, only a
      few studies have assessed the extent to which sport expert skills in wagering are
      a manifestation of the illusion of control. This study examined (a) whether
      expert hockey bettors could make better predictions than chance, (b) whether
      expert hockey bettors could achieve greater monetary gains than chance, and (c)
      what kind of strategies hockey gamblers rely on when betting. Accordingly, 30
      participants were asked to report their state lottery hockey bets on 6 occasions.
      We suggest that the information used by bettors, along with near-misses,
      reinforces their perception of expertise. The results of this experiment suggest
      that the so-called "skills" of the sports bettors are cognitive distortions.

PMID- 15238057
TI  - Assessment of substance cue reactivity: advances in reliability, specificity, and
      validity.
AB  - An arousal-control and cross-over design was used to evaluate the reliability,
      specificity, and validity of the Normative Appetitive Picture System (NAPS), a
      cue exposure protocol with sets of visual alcohol, cigarette, and control cues.
      The authors also examined the utility of conceptualizing cue reactivity as a
      multidimensional phenomenon involving independent approach and avoidance
      dimensions. University student participants (n=369) rated multiple cue images in
      terms of arousing properties and capacity to elicit separate approach and
      avoidance inclinations. They also completed a battery of substance-related
      individual-difference measures. Results indicated that NAPS protocol reactivity
      profiles had good reliability and high specificity across cue types and
      individuals with different substance use histories. Avoidance reactivity
      independently predicted self-reports of substance-related behaviors, after
      controlling for approach reactivity.

PMID- 15238058
TI  - Psychiatric comorbidity and substance use treatment outcomes of adolescents.
AB  - Treatment outcomes of 126 adolescents (13-18 years old) with comorbid substance
      use disorders (SUDs) and Axis I psychiatric disorders (mood, anxiety, conduct,
      and attention-deficit/hyperactivity disorders) were compared to 81 SUD
      adolescents with no additional Axis I disorder. Participants completed structured
      interviews and symptom measures while participating in an adolescent treatment
      program and at 6 months following treatment. Results indicated that comorbid
      youth received more treatment during the outcome period; despite this, more
      comorbid SUD-Axis I disordered adolescents used substances following treatment
      than SUD-only youth, even after controlling for socioeconomic status and
      ethnicity. Among comorbid youth, internalizing disordered adolescents were less
      likely to use substances during the follow-up period, and externalizing
      disordered youth returned to substance use most rapidly after discharge from
      treatment.

PMID- 15238059
TI  - Psychosocial variables associated with adolescent gambling.
AB  - The authors empirically examined the relations between several psychosocial
      variables associated with adolescent problem gambling. Participants were 2,336
      students in Grades 7-13, and all completed a questionnaire regarding gambling
      activities, gambling severity, perceived social support, drug and alcohol
      dependence, and various social, emotional, and behavioral problems. With respect
      to gambling severity, 4.9% of adolescents met the criteria for pathological
      gambling, and 8.0% were found to be at risk. Psychosocial difficulties associated
      with problem gambling include poor perceived familial and peer social support,
      substance use problems, conduct problems, family problems, and parental
      involvement in gambling and substance use. A set of predictor variables that may
      lead to problem gambling includes having family problems, having conduct
      problems, being addicted to drugs or alcohol, and being male.

PMID- 15238060
TI  - Physical and sexual intimate partner violence among women in methadone
      maintenance treatment.
AB  - Although several studies have examined the relationship between intimate partner
      violence (IPV) and drug use among women in drug treatment programs, more
      information is needed to delineate differences, as a function of the specific
      drug used. Data from a random sample of 416 women attending methadone programs
      were analyzed to elucidate the differential associations between IPV and use of
      the following: marijuana only, cocaine only, heroin only, or cocaine and heroin.
      Prevalence of IPV among this sample far exceeded estimates from the general
      population. After adjusting for sociodemographic variables, use of cocaine only
      was significantly associated with an increased likelihood of experiencing IPV
      compared with no drug use. Similar results were found for women using both
      cocaine and heroin.

PMID- 15238061
TI  - Psychometric evaluation of self- and collateral timeline follow-back reports of
      drug and alcohol use in a sample of drug-abusing and conduct-disordered
      adolescents and their parents.
AB  - One hundred eighty-eight drug-abusing and conduct-disordered adolescents and
      their parents provided retrospective reports of the youths' frequency of alcohol
      and illicit drug use for each of the 6 months preceding their initial session in
      an outpatient treatment program. Youths' and parent reports of youths' drug and
      alcohol use for each month were similar. For marijuana and alcohol, frequency
      reports were related for each month, whereas hard drug reports were related only
      for the 4 months preceding intake. Relationships among alcohol and hard drug
      reports were strong during Months 1, 2, and 4 preceding intake, whereas strength
      of relationship among marijuana reports was similar throughout the 6 months.

PMID- 15238062
TI  - Effects of alcohol on risk-seeking behavior: a group-level analysis.
AB  - Although much drinking occurs in social settings, there has been little testing
      of alcohol in groups. The authors examined the effects of alcohol on performance
      on a group decision-making task. Fifty-four unacquainted male social drinkers
      were randomly assigned to 3-person groups that consumed either alcohol (0.82
      g/kg) or a placebo. After drinking, participants decided whether to complete a 30
      min questionnaire battery or toss a coin and, pending the outcome of that toss,
      complete either no questionnaires or a 60-min battery. Alcohol groups were
      significantly more likely than placebo groups to choose the coin toss. Results
      highlight the potent effects of alcohol on group decision making and suggest that
      application of social psychological theory and methods to the study of alcohol is
      warranted.

PMID- 15238063
TI  - Depressed mood and smoking experimentation among preteens.
AB  - The authors examined children's depressed mood, parental depressed mood, and
      parental smoking in relation to children's smoking susceptibility and
      experimentation over 20 months in a cohort of 418 preteens (ages 10-12 at
      baseline) and their parents. Depressed mood in preteens was strongly related to
      experimentation but not to susceptibility. In cross-sectional analyses parental
      depressed mood was related to children's experimentation, but in longitudinal
      analyses parental depressed mood at baseline did not differentiate children who
      experimented from those who did not. Although parental smoking was strongly
      related to experimentation, it was not related to susceptibility either cross
      sectionally or longitudinally. Depressed mood among preteens and parents appeared
      to be more strongly related to children's smoking behaviors than to their
      intentions to smoke.

PMID- 15238064
TI  - If the "adaptive" immune system can recognize a significant portion of the
      pathogenic universe to which the "innate" immune system is blind, then...
AB  - The "adaptive" immune repertoire functionally recognizes pathogens (and their
      toxic products) that the "innate" defense system misses. This requires that the
      self-nonself discrimination and the regulation of effector output be dependent
      primarily on somatic learning mechanisms (i.e. on the somatically generated,
      large, random "adaptive" immune paratopes repertoire).

PMID- 15238065
TI  - Response to Cohn: The immune system rejects the harmful, protects the useful and
      neglects the rest of microorganisms.
AB  - The immune system is seen as a guardian of tissue integrity. It would analyse the
      extent and quality of damage and respond adequately. If no ill effects were
      found, the system would ignore disturbance, but if beneficial effects were found,
      it could protect certain microorganisms (establishing commensalism), perhaps via
      regulatory cells. The Integrity hypothesis proposes three basic groups of
      intercellular signals for cells of all tissues and assumes that they govern
      communication between dendritic cells, T cells and B cells. Signal-1 would be the
      main information source resulting with generation of intracellular mediators that
      are bound to travel into the nucleus to achieve reaction. Signal-2 represents the
      generation of additional signal transducers representing a modifier at the level
      of cytosol. And, signal-3 would be a modifier at nuclear level, perhaps guarding
      accessibility to chromosome or genetic locus.

PMID- 15238068
TI  - On immunity against infections and vaccines: credo 2004.
AB  - Resistance of vertebrate hosts against infections comprises important natural or
      innate resistance combined with adaptive immune responses of T and B cells.
      Viruses, bacteria or classical parasites all probe the limit of immune responses
      and of immunity. They, therefore, offer an excellent opportunity to assess the
      biology, physiology and molecular aspects of immune responses and help in
      characterizing the three basic parameters of immunology-- specificity, tolerance
      and memory. Various experiments are summarized that indicate that the rules of
      antiviral, antitumour, antiorgan graft and of autoimmune responses are basically
      the same. The practical specificity repertoire of T and B cells is probably in
      the order of 10(4)-10(5) specificities expressed by T cells or by neutralizing
      antibodies. Tolerance is best defined by rules of reactivity to eliminate
      infections while avoiding destruction of normal cells by complete elimination of
      T cells that are specific for antigens persisting within the blood and lymphatic
      (lymphohaemopoietic) system. Induction of a T-cell response is the result of
      antigens newly entering lymph nodes or spleen, initially in a local fashion and
      exhibiting an optimal distribution kinetics within the lymphohaemopoietic system.
      Antigen staying outside lymphatic tissues are immunologically ignored (e.g. are
      non-events). Thus immune reactivity is regulated by antigen dose, time and
      relative distribution kinetics. Memory is the fact that a host is resistant
      against disease caused by reinfection with the same agent. Memory correlates best
      with antigen-dependent maintenance of elevated antibody titres in serum and
      mucosal secretions, or with an antigen-driven activation of T cells, such that
      they are protective immediately against peripheral reinfections in solid tissues.
      While antibodies transferred from mother to offspring are a prerequisite for the
      survival of otherwise unprotected immuno-incompetent offsprings, activated memory
      T cells cannot be transmitted. Thus, attenuation of infections in newborns and
      babies by maternal antibodies is the physiological correlate of man-made
      vaccines. T cells not only play an essential role in maintaining T-help-dependent
      memory antibody titres, but also in controlling the many infections that persist
      in a host at rather low levels (such as tuberculosis, measles and HIV).

PMID- 15238069
TI  - Activation of natural killer cells: underlying molecular mechanisms revealed.
AB  - Natural killer (NK) cells, the third major lymphocyte population, are important
      effector cells against certain infections and tumours. They have also been
      implicated as a link between innate and adaptive immune responses. In recent
      years, much attention has been paid to the NK cell inhibitory receptors and their
      interaction with major histocompatibility complex class I molecules on target
      cells. This review summarizes recent findings on regulation of NK cell activity
      with an emphasis on NK cell stimulatory receptors. A particular emphasis is
      devoted to the receptor NKG2D that is expressed on all NK cells.

PMID- 15238070
TI  - The potential role of mannan-binding lectin in the clearance of self-components
      including immune complexes.
AB  - Mannan-binding lectin (MBL) is a pattern recognition receptor in the innate
      immune system. It recognizes certain sugar residues arranged in a pattern that
      enables MBL to bind with sufficient strength. Such sugar patterns are common on
      the surface of many microorganisms, and MBL has therefore been considered to be
      an agent that can discriminate between self and nonself. There is, however,
      increasing evidence supporting that MBL, like many membrane-bound C-type lectin
      like receptors, also helps to dispose of various outworn or abnormal body
      components. Most self-components are protected with sialic acid or galactose that
      disrupt the pattern of the sugars that MBL can bind, but MBL may be significantly
      involved in the elimination of self-components that have lost these protective
      terminal residues. The role of MBL in the clearance of invading pathogens has
      previously been thoroughly reviewed. Here, we review some findings that support
      the notion that MBL may contribute to noninflammatory removal of immune complexes
      and abnormal cells by the reticuloendothelial system. Defects in this clearance
      mechanism may cause an accumulation of potentially dangerous self-components,
      thereby increasing the likelihood of chronic inflammation and autoimmunity.

PMID- 15238071
TI  - Fibronectin receptor defects in NOD mouse leucocytes: possible consequences for
      type 1 diabetes.
AB  - Integrins of the very late antigen (VLA) family mediate leucocyte traffic to
      lymphoid organs under physiological conditions and in chronic inflammatory
      situations such as autoimmunity. Accordingly, the current thinking is of a
      positive correlation between VLA expression and capability of the generation of
      autoimmunity. Herein we discuss recent findings on the defective expression of
      integrin-type fibronectin receptors alpha4beta1 (VLA-4) and alpha5beta1 (VLA-5)
      in the non-obese diabetic (NOD) mouse, a murine model of autoimmune insulin
      dependent diabetes mellitus. As compared with normal animals, NOD thymocytes
      (including the CD4+CD25+ regulatory T cells) exhibit a decrease in the membrane
      expression of alpha5beta1, resulting in a functional impairment of fibronectin
      mediated interactions, including cell migration. Interestingly, thymocytes that
      are trapped within the giant perivascular spaces seen in NOD thymus are
      consistently alpha5beta1 negative, suggesting that the progressive arrest of
      mature cells can be related to the alpha5beta1 defect. Peripheral T cells also
      exhibit decreased alpha5beta1 membrane expression and impaired fibronectin-driven
      migration. Additionally, we observed a defect in alpha4beta1 fibronectin receptor
      expression in NOD macrophages. Peritoneal, bone marrow-derived-precursor, as well
      as thymic macrophages of NOD mice showed an impaired upregulation of alpha4
      integrin chain expression, dependent on the level of macrophage maturation.
      Overall these data lead to the notion that NOD leucocytes bear distinct
      fibronectin receptor-mediated cell migration defects, which may be involved in
      the pathogenesis and/or pathophysiology of the autoimmune events seen in NOD
      mice. Further studies will be helpful to define whether or not this concept can
      be applied for other autoimmune diseases.

PMID- 15238072
TI  - Current gene-mapping strategies in experimental models of multiple sclerosis.
AB  - Both family-based linkage analyses and population-based association studies have
      failed to identify disease-regulatory non-human leucocyte antigen genes of
      importance in multiple sclerosis (MS). Instead, investigators have employed
      experimental models, which offer major advantages in genetic studies. We
      summarize the current main methodologies used and the status of both the human
      and experimental approaches. Why is it important to find genes regulating MS?
      There is an immense number of cellular and molecular interactions defined in the
      immunological field and it is very difficult to unravel those that are critical
      to an inflammatory disease, such as MS, by classical hypothesis-driven research.
      Unbiased genetics defines evolutionary conserved gene polymorphisms and pathways
      regulated by these genes, which are central in the pathogenesis. These, in turn,
      are of interest as therapeutic targets and pharmacogenetic markers.

PMID- 15238073
TI  - Lupus glomerulonephritis revisited 2004: autoimmunity and end-organ damage.
AB  - Histopathology of the kidney and clinical presentation are critical factors in
      the diagnosis of immune-mediated glomerulonephritis (GN). The histological
      manifestations of glomerular injury are shared by multiple underlying mechanisms.
      Work from our laboratory and from other investigators shows that antinuclear,
      antihistone or anti-dsDNA antibodies are neither required nor sufficient for
      development of lupus GN. In addition, antibody to dsDNA can be generated by
      mechanisms other than loss of tolerance to chromatin. Genetic analyses
      demonstrate that although there is some interaction between autoantibody
      production and renal disease, the phenotypes are regulated by distinct genetic
      intervals. Furthermore, renal failure is not an essential outcome of the immune
      complex deposition and proliferative lupus GN. These data are also supported by
      published studies from systemic lupus erythematosus (SLE) patients. The immune
      regulation of lupus GN is distinct from other organ-specific diseases and not
      influenced by CD25(+) or NK1.1(+) regulatory T cells. Thus, fatal GN may depend
      upon a kidney-reactive T-cell response that, in turn, may be regulated by gender
      and intrinsic end-organ factors. The data discussed in this review call for a re
      evaluation of the current paradigms for pathogenesis of SLE. An interactive model
      separating autoimmunity from end-organ susceptibility for the pathogenesis of SLE
      is proposed.

PMID- 15238074
TI  - Interleukin-2, but not interleukin-15, is required to terminate experimentally
      induced clonal T-cell anergy.
AB  - It has been demonstrated that T cells stimulated with nucleosome-polyomavirus T
      antigen (self-nonself) complexes, but not nucleosomes, activate autoimmune
      nucleosome-specific T cells. As these cells may be naive, such observations do
      not show that anergic T cells are reactivated. To understand the regulation of
      autoimmunity, this is important to assess, and this is the focus of this study. T
      cell anergy was induced by antigen stimulation in the presence of antibodies to
      the costimulatory molecules CD80/CD86. Requirements for the reactivation of
      anergic T cells were analysed by the ability of antigen and interleukin-2 (IL-2)
      or IL-15 to increase T-cell proliferation and IL-2 transcription. Data
      demonstrate that stimulation of T cells with T-antigen and anti-CD80/86
      antibodies promotes long-lasting clonal T-cell anergy. While T-antigen did not
      reactivate anergic T cells, proliferation and upregulation of IL-2 gene
      transcription was initiated by stimulation with antigen, costimulation and IL-2
      added to the cultures. Proliferation per se was not sufficient to promote the
      reactivation of anergic T cells, as both IL-2 and IL-15 induced proliferation,
      while antigen and IL-2, but not IL-15, upregulated IL-2 mRNA levels. These data
      demonstrate that the innate immune system and IL-2 are central to the initiation
      and termination of T-cell anergy.

PMID- 15238075
TI  - Monocytes stimulated with group B streptococci or interferons release tumour
      necrosis factor-related apoptosis-inducing ligand.
AB  - Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a
      cytotoxic member of the TNF family. Some reports have shown that TRAIL is
      released from cells in a soluble form. In this work, we have investigated the
      mechanism of release of TRAIL from monocytes. First, we show that whole gram
      positive, gram-negative and mycoplasmal bacteria as well as lipopolysaccharide
      (LPS), interferon-alpha (IFN-alpha), -beta and -gamma all induced upregulation of
      TRAIL on the surface of human monocytes. Next, we show that IFN-alpha, -beta and 
      gamma all induced a dose-dependent release of TRAIL, giving significant amounts
      of soluble TRAIL after 2 days. Of the bacteria, only the Group B streptococcus
      COH-1 (GBS) induced release of TRAIL and concomittantly induced IFN-alpha.
      Monocytes stimulated with GBS or IFN-alpha also showed extensive cell death. When
      monocyte apoptosis was prevented by interleukin-1, GM-CSF, LPS or the caspase
      inhibitor zVADfmk, the IFN-alpha-induced release of TRAIL was reduced, whereas
      agents inducing necrosis caused increased release of TRAIL. LPS also prevented
      release of TRAIL from GBS-stimulated monocytes. The release of TRAIL from IFN
      alpha-stimulated monocytes was reduced by inhibitors of both cysteine and
      metalloproteases. We conclude that bacteria and IFN induce upregulation of
      membrane TRAIL and that release of TRAIL is associated with cell death.

PMID- 15238076
TI  - Antigen-specific in vitro suppression of murine Helicobacter pylori-reactive
      immunopathological T cells by CD4CD25 regulatory T cells.
AB  - A Helicobacter pylori-specific in vitro coculture system was established and used
      to study the role of CD4+CD25+ regulatory T cells (Treg) in gastritis development
      in mice with H. pylori infection. Effects of therapeutic immunization against H.
      pylori infection on the Treg function were also studied to better understand the
      mechanisms leading to postimmunization gastritis in these mice. Depletion of Treg
      led to extensive proliferation to H. pylori antigens of CD4+ T cells isolated
      from either naive, H. pylori-infected or H. pylori-immunized mice. Using the Treg
      depleted CD4+ T cells from immunized mice as effector cells, we compared the
      suppressive efficacy of Treg isolated from naive, infected or immunized mice and
      found that Treg from naive mice, and slightly less efficiently from infected
      mice, suppressed the CD25- effector T-cell response and in most cases were
      distinctly more efficacious than Treg isolated from immunized mice. The
      suppressive efficacy of Treg isolated from the differently treated mice
      correlated closely with production of interleukin-5 (IL-5) by the Treg and
      suppression of interferon-gamma and IL-2 production by the CD25- effector T
      cells. Our study is the first to demonstrate in H. pylori-induced chronic
      infection, antigen-specific Treg with differential efficacy in suppressing H.
      pylori proinflammatory T effector cells.

PMID- 15238077
TI  - Defective clearance of adenovirus in IRF-1 mice associated with defects in NK and
      T cells but not macrophages.
AB  - A replication-defective adenovirus-LacZ recombinant virus (AdLacZ) was injected
      intravenously into IRF-1(-/-) mice and wild-type mice to characterize the
      contribution of IRF-1 to the immune-mediated clearance of Ad vector. Compared
      with wild-type mice, IRF-1(-/-) mice expressed higher levels of the LacZ gene
      product in the liver. After infusion of the AdLacZ, the expression of IRF-1 mRNA
      was upregulated in the liver of wild-type mice, but not in IRF-1(-/-) mice. Both
      spleen and liver mononuclear cells from IRF-1(-/-) mice initially exhibited a
      markedly lower number of NK, NK-T and CD8 T cells. At day 7 after the
      administration of AdLacZ, there was a significantly increased population of NK,
      NK-T and CD8 T cells in both spleen and liver, and also CD11b(+) cells in liver
      of IRF-1(-/-) mice, compared with the increased in wild-type mice. As IRF-1 is an
      important signal for production of IFN-gamma by CD8 T and NK cells as well as
      production of IL-12 by CD11b(+) cells, we determined whether there were lower
      levels of these cytokines in IRF-1(-/-) mice after Ad challenge. Surprisingly,
      there were lower levels of IL-12, but higher levels of IFN-gamma and IL-18 in IRF
      1(-/-) compared with wild-type mice at day 7 after administration with AdLacZ.
      These results indicate that delayed clearance of Ad is associated with partial
      correction of defects of the NK, NK-T and CD8 T cells and increased production of
      IFN-gamma and IL-18 in IRF-1(-/-) mice.

PMID- 15238078
TI  - Avian Helios and evolution of the Ikaros family.
AB  - Abstract Helios (Znfn1a2) is an Ikaros-related lymphoid regulatory protein with
      possible involvement in T-cell development and function as well as in the early
      events of haematopoietic stem cell differentiation. To evaluate the role of
      Helios in avian haemato/lymphopoiesis, we have characterized the avian Helios
      gene. In contrast to studies in mouse and human, we have found that the highly
      conserved avian Helios encodes a novel exon and three isoforms. Furthermore, the
      avian Helios expression precedes Ikaros in the ontogeny, being present already on
      the first day of embryonic development. Additionally, expression in the bursa of
      Fabricius, germinal centres and B-cell lines suggests a role for Helios also in
      the B-cell lineage. Phylogenetic studies of the Ikaros family along with data on
      paralogous chromosome segments in the human genome connect the expansion of the
      Ikaros family and thus possibly the emergence of the adaptive immune system with
      the putative second round of genome duplications and indicate that the Ikaros
      gene family is linked with the Hox gene clusters.

PMID- 15238079
TI  - Immunoglobulin heavy-chain receptor editing is observed in the NOD/SCID model of
      human B-cell development.
AB  - Receptor editing and receptor revision are the two mechanisms of antibody
      diversity that result in either complete V-gene replacement or the formation of
      hybrid V genes. We do not yet understand how this process unfolds, because they
      are rare and difficult to study in vivo. In this study, we describe a family of
      VH4-34:VH4-61 hybrids isolated from a human B-cell chimeric non-obese
      diabetic/severe combined immunodeficient mouse. The observation of hybrid
      immunoglobulin sequences in human B cells that developed in this model system
      makes it useful for the study of this mechanism of diversification and tolerance.

PMID- 15238081
TI  - Antinucleosome autoantibodies bind directly to cell lines in vitro and via the
      FcgammaRIIB receptor to B lymphocytes in vivo: a role for immune complexes in
      interactions between antinucleosome IgG2a and B cells of BXSB lupus mice.
AB  - The initial novel observation of this study was that most B cells of male BXSB
      lupus mice bear surface IgG2a(b) of extrinsic origin. To define the surface
      antigen, we here examine three (NZBxBXSB)F1-derived IgG2a(b) monoclonal
      antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three
      mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and
      an early target of autoimmunity in systemic lupus erythematosus. Their tentative
      dissociation constant (K(d)) for soluble nuc particles was approximately 7 x 10(
      10) m. The mAbs bound more weakly to both H2A-H2B-DNA and H3-H4-DNA complexes,
      and in immunoblot they stained all four core histones. The mAbs detected a
      surface antigen on all cell lines examined, present on viable cells. When
      stripped of nuc, and in the presence of DNase I, their binding to cell lines
      improved. Heparin displaced the antigen from the cell surface. In vivo, the three
      mAbs stained B cells of several BALB/c mice clearly stronger than the isotype
      control; this differential staining was significantly reduced in FcgammaRIIB
      deficient mice. The results indicate that the three mAbs recognize (a) planted
      antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to
      immune complexes that bind to FcgammaRIIB. Further experiments demonstrated that
      antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence,
      at least part of the extrinsic IgG2a(b) found on BXSB B cells may represent
      FcgammaRIIB-bound nuc-IgG2a(b) complexes.

PMID- 15238080
TI  - Citrullination of self-proteins and autoimmunity.
AB  - Citrullination (deimination is an enzymatic, posttranslational conversion of
      arginine residues to citrulline residues) of joint-associated self-proteins may
      be a possible mechanism in the induction of autoimmune CD4 T-cell responses in
      rheumatoid arthritis. We have studied the immune response to normal or deiminated
      human fibrinogen (hFBG) in mouse strains expressing major histocompatibility
      complex (MHC) class II antigens similar to either RA-susceptible or non
      susceptible HLA-DR4 alleles. Upon immunization with deiminated hFBG, all mouse
      strains analysed produced high amounts of anti-FBG antibodies, while relatively
      low levels of anti-citrulline antibodies and little or no anti-FBG antibodies
      crossreactive with mouse FBG (mFBG) were obtained. Mice immunized with normal
      hFBG also produced high amounts of anti-hFBG antibodies. However, whereas mice
      with MHC class II molecules similar to RA-non-susceptible HLA-DR4 alleles
      produced low levels of anti-hFBG antibodies with crossreactivity to mFBG, mouse
      strains with RA-susceptible HLA-DR4-equivalent MHC class II molecules contained
      high levels of such crossreactive anti-mFBG antibodies. Similar results were
      obtained with HLA-DR4*0401, human CD4-double-transgenic mice. However, none of
      the more than 600 mice investigated developed arthritis. These data indicate that
      the quality and/or quantity of anti-FBG autoantibodies or of anti-citrulline
      antibodies, produced in the studied mouse strains, are insufficient to induce
      arthritis.

PMID- 15238082
TI  - Inhibition of the proteasome reduces transfer-induced diabetes in nonobese
      diabetic mice.
AB  - Inhibition of the 26S proteasome reduces the severity of several immune-mediated
      diseases. Here, we report that the proteasome also regulates transfer-induced
      diabetes in nonobese mice. Treatment of recipient mice with the proteasome
      inhibitor N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal (MG132)
      resulted in a 76% reduction in transfer-induced diabetes. The closely related
      inhibitor carbobenzoxy-l-leucyl-l-leucinal that inhibits calpains but not the
      proteasome had no protective effect, suggesting that MG132 acted via inhibition
      of the proteasome. MG132 decreased proliferation of transferred T cells in the
      pancreatic lymph nodes in vivo and prevented their expansion in a dose-dependent
      manner in vitro, consistent with a direct effect by MG132 on the T cells. MG132
      did not prevent migration of transferred T cells into the islets but reduced the
      number of mice with severe infiltration. We suggest that MG132 prevents transfer
      induced diabetes by directly targeting the autoreactive T cells and lowering
      their diabetogenic potential.

PMID- 15238083
TI  - Anti-class II antibodies, but not cytotoxic T-lymphocyte antigen 4-immunoglobulin
      hybrid molecules, prevent rejection of major histocompatibility complex class II
      negative myeloma in T-cell receptor-transgenic mice.
AB  - We have previously shown that tumour-specific CD4+ T cells protect against
      subcutaneous injections of major histocompatibility complex (MHC) class II
      negative MOPC315 myeloma cells. Here, we have interfered with the immunologic
      events that lead to successful rejection of MOPC315 challenges in T-cell receptor
      (TCR)-transgenic mice. The CD4+ T cells have a transgene-encoded TCR specific for
      a MOPC315 V-region idiotypic (Id) peptide presented on the MHC class II molecule
      E(d). A side-by-side comparison indicated that DNA-recombination-deficient TCR
      transgenic mice were better protected against MOPC315 tumour development than
      recombination-sufficient counterparts, suggesting that B cells or endogenous TCR
      chains might facilitate tumour progression in this model. Intraperitoneal
      injections of E(d)-specific antibodies over a period of initial 24 days,
      abrogated protection against tumours in both strains of mice. By contrast,
      injections of anticostimulatory molecules (cytotoxic T-lymphocyte antigen 4
      immunoglobulin hybrid molecules) had no effect. The findings demonstrate that
      tumour rejection depends on the presence of MHC class II molecules, despite the
      fact that MOPC315 tumour cells themselves do not express them. The results are
      consistent with the idea that secreted myeloma protein is processed and presented
      by class II+ antigen-presenting cells to Id-specific naive CD4+ T cells that
      become activated and kill the myeloma cells by a bystander mechanism. While Id
      presentation on class II molecules is absolutely required for tumour rejection,
      costimulatory CD80/CD86 molecules might be dispensible in this process.

PMID- 15238084
TI  - Phenotype and natural killer cell sensitivity of a radiation-induced acute T-cell
      leukaemia (Roser leukaemia) in PVG rats.
AB  - A radiation-induced T-cell leukaemia [Roser leukaemia (RL)] in the rat was
      conditioned for growth in vitro by repeated in vivo-in vitro passages. This in
      vitro cell line, termed RL-T, maintained its leukaemia-inducing property when
      transferred to syngeneic PVG rats. It expresses several T-cell markers and the T
      cell alpha/beta receptor-CD3 complex. RL-T, furthermore, expresses major
      histocompatibility complex (MHC) I antigens, both classical (RT1.A) and
      nonclassical (RT1.C), which makes it susceptible to killing by alloreactive
      natural killer cells in vitro.

PMID- 15238085
TI  - Release of DNA from dead and dying lymphocyte and monocyte cell lines in vitro.
AB  - DNA is a nuclear macromolecule that circulates in the blood where its levels can
      reflect the activity of inflammatory and malignant diseases. While dead and dying
      cells have usually been considered the source of blood DNA, the mechanisms for
      its release during apoptosis and necrosis are not well defined. To elucidate DNA
      release, an in vitro model system was used, assessing DNA in the media of living,
      apoptotic or necrotic Jurkat and U937 cells. Apoptosis was induced by etoposide,
      camptothecin or staurosporine, while necrosis was induced by heating at 56
      degrees C. DNA release was measured by fluorometry with the dye PicoGreen while
      the extent of death was measured by fluorescence-activated cell sorter analysis
      with propidium iodide and annexin. Apoptotic Jurkat cells released significantly
      more DNA in the media than untreated cells while necrotic cells did not show
      significant DNA release. U937 cells showed similar findings. Pretreatment of
      Jurkat cells with z-VAD-fmk, a caspase inhibitor, reduced both apoptosis and DNA
      release. By gel electrophoresis, extracellular DNA from apoptotic cells showed
      laddering with low molecular weight fragments. These studies suggest that
      extracellular release of DNA is a consequence of apoptosis and may account for
      some of the DNA in the blood.

PMID- 15238086
TI  - Cytolytic capabilities of lamina propria and intraepithelial lymphocytes in
      normal and chronically inflamed human intestine.
AB  - Cell-mediated lymphocyte cytotoxicity in ileum and colon of patients with
      ulcerative colitis (UC), Crohn's disease (CD) and controls was investigated.
      Frequencies of cells expressing perforin and Fas-ligand (FasL) were determined by
      immunomorphometry. mRNA expression of perforin, granzyme B and FasL in T cells
      and subsets was assayed by reverse transcriptase-polymerase chain reaction.
      Cytotoxicity of intraepithelial and lamina propria lymphocytes was analysed
      without ex vivo activation in three functional assays: (1) anti-CD3-dependent T
      cell receptor (TCR)-/CD3-mediated redirected cytotoxicity, (2) Fas-/FasL-mediated
      TCR-/CD3-independent cytotoxicity and (3) natural killer (NK) cell cytotoxicity.
      Inflammation in ileum of CD patients caused increased frequency of perforin
      expressing cells and enhanced perforin-dependent TCR-/CD3-mediated cytotoxicity.
      In contrast, lymphocytes in the inflamed colon of UC or Crohn's colitis patients
      did not display this cytotoxicity nor did lymphocytes of normal colon. Normal
      colon lymphocytes showed spontaneous Fas-/FasL-mediated cytotoxicity. This
      activity was retained but not enhanced in inflamed UC colon. In contrast, a
      significant increase of FasL-expressing cells was seen in situ. Inflammation did
      not induce NK cell activity in colonic lymphocytes. Intestinal lymphocytes
      comprise effectors active in two different cytolytic processes. 'Classical'
      cytotoxic T lymphocytes in small intestine and lymphocytes executing TCR-/CD3
      independent FasL-/Fas-mediated killing of unknown biological role present
      throughout the intestinal mucosa. Ongoing normal cytolytic processes seem to be
      enhanced by chronic inflammation.

PMID- 15238088
TI  - Mannan-binding lectin and RSV lower respiratory tract infection leading to
      hospitalization in children: a case-control study from Soweto, South Africa.
AB  - Respiratory syncytial virus (RSV) is the most important microbiological cause of
      lower respiratory tract infection (LRTI) in infants. Mannan-binding lectin (MBL)
      is believed to play a major protective role in the vulnerable period in infancy
      where the maternal antibodies have been catabolized, and the adaptive immune
      system has not yet matured. Mutations in the promoter region and in exon 1 of the
      gene-encoding MBL result in low serum levels of MBL. MBL deficiency is the most
      common immunodeficiency on the African Continent with frequencies of the variant
      alleles up to 0.29. We investigated whether MBL deficiency has an impact on the
      hospitalization for LRTI caused by RSV in infants from Soweto, South Africa. The
      cases were ethnic black Africans identified through surveillance for RSV-LRTI at
      Chris Hani Baragwanath Hospital, Soweto, and the controls were sampled from four
      immunization clinics in the area. Fifty-five cases and 113 age- and sex-matched
      controls were identified. Seventy-six per cent were under 6 months of age, and
      42% (n = 23) were under 3 months of age. No association was found between low
      levels of MBL or carriage of variant alleles and LRTI caused by RSV, odds ratio
      (OR) 1.00 (CI 0.99-1.03) and OR 1.24 (0.73-2.12). We did not find support for the
      hypothesis that MBL deficiency leads to the hospitalization for LRTI caused by
      RSV.

PMID- 15238087
TI  - Statin drugs do not affect serum complement activation in vitro.
AB  - Statin drugs prevent coronary heart disease through anti-inflammatory mechanisms
      in addition to the well-known reduction of low-density lipoproteins. The
      complement system plays an essential role in the inflammatory response and has
      been postulated to be modified by statins. A direct role for statins in
      complement activation, however, has not been previously investigated. We
      therefore studied the effect of statins on in vitro complement activation.
      Pravastatin, atorvastatin and the active metabolite of the latter, ortho-hydroxy
      atorvastatin, were added to normal human serum and incubated for 1 h in the
      absence or presence of aggregated immunoglobulin (classical pathway activation)
      or cobra venom factor (alternative pathway activation). The degree of complement
      activation, as detected by specific complement-activation products for the
      classical pathway (C1rs-C1-inhibitor complexes), the combined classical and
      lectin pathway (C4bc), the alternative pathway (C3bBbP) and the final common
      pathway (C3bc and TCC), was not affected by pre-incubation of the serum with any
      of the statins. Statins do not affect complement activation directly, but
      indirect effects in vivo may well be operative.

PMID- 15238089
TI  - Characterization of ribosomal P autoantibodies in relation to cell destruction
      and autoimmune disease.
AB  - Autoantibodies against the ribosomal P proteins are related to cell death and
      tissue destruction and are frequently exhibited in patients with systemic lupus
      erythematosus (SLE). In an attempt to explore the effect of tissue destruction on
      the induction of anti-P autoantibodies, we searched for anti-P autoantibodies by
      enzyme-linked immunosorbent assay in 201 antinuclear antibody (ANA)-positive
      individuals, in 10 patients with treated kidney SLE and in 45 acute leukaemia
      patients undergoing intensive chemotherapy. The autoantibody reactivity was
      further characterized using one- and two-dimensional immunoblot analysis and
      immunofluorescence. Anti-P were detected in 5.5% (11/201) of ANA-positive
      individuals, but not in kidney-affected SLE patients or in patients with
      leukaemia. Seven of 11 anti-P-positive patients had SLE (3/11), primary
      Sjogrens's syndrome (1/11) and other autoimmune diseases (3/11). A relation
      between disease activity and anti-P was suggested by follow-up examinations in
      one SLE patient, supported by the absence of anti-P autoantibodies in the 10
      treated kidney SLE patients. Anti-P autoantibodies were detected by immunoblot in
      one patient with SLE indicating anti-P2 predominance and in the patient with
      Sjogrens's syndrome indicating anti-P1 predominance. Diverging humoral responses
      in these ANA- and anti-P-positive patients were further illustrated by
      immunofluorescence, elucidating varying nuclear reactivity and anti-P pattern.
      The observation of anti-P in individuals with active autoimmune disease, but not
      in patients with chemotherapy-induced cell damage, suggests that anti-P
      antibodies are part of a specific disease process, and not elicited as a response
      to cell destruction per se.

PMID- 15238090
TI  - CD28nullCD4+ T cells--characterization of an effector memory T-cell population in
      patients with rheumatoid arthritis.
AB  - CD4+ T cells lacking the costimulatory molecule CD28 have been described both in
      elderly individuals and in chronic inflammatory disorders, one being rheumatoid
      arthritis (RA). We, in this study, provide a comprehensive characterization of
      cell surface markers on and function of such CD28nullCD4+ T cells, as well as
      correlations with clinical parameters. We conclude that of all surface markers
      associated with these cells, only CD57 and CD11b are expressed on the majority of
      them. This CD28null population occurred in one-third of patients with RA and was
      independent of clinical characteristics. The population was persistent and
      expanded in peripheral blood, but was excluded from the joint in most patients.
      Functionally, CD28nullCD4+ T cells were potent effector memory cells with regard
      to their proliferation and cytokine-secretion profiles. This capacity correlated
      with a hitherto unpublished surface phenotype, the cells being uniformly CCR7-
      and CD43high. Moreover, a new terminally differentiated CD45RA+CCR7- population
      of CD4+ T cells was identified. We would like to suggest that in the unbalanced
      immune system of patients with autoimmune disease and chronic infection an
      expanded CD28nullCD4+ T-cell population able to secrete high levels of cytokines
      is likely to contribute to disease manifestations.

PMID- 15238092
TI  - The ozone layer.
AB  - BACKGROUND/PURPOSE: The intention of this paper is to stimulate the interest for
      the ozone layer, especially among young colleagues in photobiology; the "layer"
      is not only important, but also fascinating. CONCLUSION: In spite of remarkably
      effective action, the recovery of the ozone layer will be a long-term process. It
      will need the attention, also of scientists, for decades to come.

PMID- 15238091
TI  - Apoptotic effect of rituximab on peripheral blood B cells in rheumatoid
      arthritis.
AB  - Rituximab (RTX) has proven efficacious in the treatment of rheumatoid arthritis
      (RA). Herein, we assessed the apoptosis-inducing capability of RTX in vitro on RA
      peripheral blood B-cell subsets and also compared the effects of RTX on B cells
      from rheumatoid factor-positive (RF+) and RF- patients. The likely relevance of B
      cells in disease was assessed by measuring B-cell-modulating serum cytokines.
      Peripheral blood B cells were isolated and cultured with the presence or absence
      of RTX. The levels of apoptosis within the naive, memory and IgD+CD27+ B-cell
      subpopulations were determined by cytofluorometric analysis and caspase 3/7
      assays. Levels of serum cytokines were measured with a multiplex cytokine array
      system. RTX induced significant apoptosis in all B-cell subsets in both RA and
      controls. In naive and memory B cells from RA patients, RTX induced significantly
      higher levels of apoptosis than in controls. RTX induced apoptosis of B cells in
      RF+ and RF- patients. Serum levels of interleukin-1beta (IL-1beta), IL-4, IL-10
      and IL-13 were profoundly increased in RF+ patients compared to RF- patients and
      controls. Although our cohort was small (10 RA patients), the data suggest that
      RTX induces apoptosis in all investigated subsets of B cells from RA patients.
      Interestingly, memory B cells from RA patients were more sensitive to RTX than
      memory cells from normal controls, suggesting that the delay in treatment
      response to RTX observed in clinical trials may be due in part to memory cell
      depletion. The apoptotic effects of RTX were similar in RF+ and RF- patients, but
      serum levels of B-cell-activating cytokine levels were only elevated in RF+ but
      not RF- patients. These data suggest that RTX is less effective in RF- RA because
      B cells play a less significant role in RA pathogenesis in RF- patients.

PMID- 15238093
TI  - Minimal erythema dose after multiple UV exposures depends on pre-exposure skin
      pigmentation.
AB  - BACKGROUND/PURPOSE: Phototherapy consists of multiple ultraviolet (UV) exposures.
      Most previous studies have focused on erythema following a single UV exposure in
      fair-skinned persons. Although it is well known that phototherapy lowers the
      daily UV-threshold dose for erythema in clinical practice, this is insufficiently
      documented under controlled experimental conditions. The purpose of this study
      was to quantify the change in the daily threshold for a dose specific erythema
      grade after 1-4 consecutive daily UV exposures. METHODS: Forty-nine healthy
      volunteers (skin type II-V) with varying pigmentation quantified by skin
      reflectance. Two UV sources were used: a narrowband UVB (Philips TL01) and a
      Solar Simulator (Solar Light Co.). Just perceptible erythema after 24 h was
      chosen as the minimal erythema dose (+); besides + and ++ were assessed. RESULTS:
      We found a positive and significant exponential relationship between skin
      pigmentation and UV dose to elicit a specific erythema grade on the back after 1
      4 UV exposures. After repetitive UV exposures the UV dose had to be lowered more
      in dark-skinned persons compared with fair-skinned persons to elicit a certain
      erythema grade. This applied to both UV sources and all erythema grades.
      CONCLUSION: In the dark-skinned persons the daily UV dose after the 4 days UV
      exposure should be lowered by 40-50% to avoid burns compared with the single UV
      exposure. For the most fair-skinned persons essentially no reduction in the daily
      UV dose was needed. Our results indicate that the pre-exposure pigmentation level
      can guide the UV dosage in phototherapy.

PMID- 15238094
TI  - In vivo measurement of 5-aminolaevulinic acid-induced protoporphyrin IX
      photobleaching: a comparison of red and blue light of various intensities.
AB  - BACKGROUND: In recent years, 5-aminolaevulinic acid (ALA) has become an
      increasingly popular photosensitizing drug for use in both photodynamic therapy
      (PDT) and photodetection (PD) of cancers. ALA metabolizes within tissue to form
      the photosensitizer protoporphyrin IX (PpIX). Like most photosensitizers, PpIX is
      fluorescent, and this fluorescence progressively decreases during PDT. This
      phenomenon is referred to as photobleaching. AIM: Our aim in carrying out this
      experiment was twofold: firstly, to compare the relative capacity of red and blue
      light to cause photobleaching; and secondly, to compare the capacity of a fixed
      light dose to cause photobleaching, when delivered at different intensities.
      METHOD: In this paper, we describe the implementation of a compact fluorescence
      spectrometer in monitoring the photobleaching of ALA-induced PpIX in vivo on the
      skin of healthy volunteers. RESULTS: We have been able to show that blue light
      causes more rapid photobleaching than red light, and that under illumination with
      red or blue light, delivery of a fixed light dose at a lower intensity results in
      more photobleaching. CONCLUSION: Comparison of the photobleaching rates suggests
      that a blue light intensity of 5 mW/cm(2) gives the same rate of photobleaching
      as the typical red light PDT intensity of 100 mW/cm(2). Further investigation of
      the correlation between PpIX photobleaching and PDT effect would be beneficial in
      interpreting the clinical significance of our findings.

PMID- 15238095
TI  - Clinical and epidemiologic characterization of photosensitivity in HIV-positive
      individuals.
AB  - BACKGROUND: An increased prevalence and severity of cutaneous photosensitivity
      has been recognized in association with human immunodeficiency virus (HIV)
      infection. However, this disorder remains poorly characterized in terms of its
      epidemiology, predisposing factors, clinical, and environmental associations.
      METHODS: To define the risk factors associated with the presence of
      photosensitivity among HIV-positive individuals, a cross-sectional study of 631
      primary patient visits to an urban HIV Dermatology clinic between January 1997
      and August 2001, inclusive, was conducted. A multivariate model was fit to
      estimate adjusted odds ratios for risk factors associated with photosensitivity
      diagnosis. Subsequently, a case-series of the patients with photosensitivity was
      reported. RESULTS: The overall prevalence of photosensitivity was 5.4%, while
      African-Americans (AA) exhibited a prevalence of 7.3%. In the multivariate model,
      using highly active anti-retroviral therapy (HAART) (OR=2.82, 95% CI: 1.13, 7.03)
      and being AA (OR=6.68, 95% CI: 1.56, 28.65) significantly increased the odds of
      photosensitivity. Patients with photosensitivity were more likely to present
      during periods of higher ultraviolet (UV) index (P=0.08). Two distinct clinical
      morphologies were noted: lichenoid and non-lichenoid, eczematous. Sub
      morphologies in the non-lichenoid group were suggestive of differences in
      immunologic profile and estimated UV exposure. CONCLUSION: Photosensitivity
      associated with HIV infection is an increasingly recognized dermatologic
      condition with a heterogeneous clinical presentation. AA ethnicity and HAART were
      independent indicators for the diagnosis of photosensitivity, whereas CD4+ and UV
      exposure had non-significant associations. The subtleties in these and other
      clinical variables may directly aid in the recognition and diagnosis of this
      poorly characterized disorder.

PMID- 15238096
TI  - Oral PUVA and topical steroids for treatment of oral manifestations of chronic
      graft-vs.-host disease.
AB  - BACKGROUND: Oral manifestations of chronic graft-vs.-host disease (cGVHD) can
      significantly affect the quality of life and severity often does not correlate
      with systemic manifestations. We evaluated the use of topical corticosteroids and
      the intraoral application of psoralen-UVA (PUVA) for treatment of oral
      manifestations of cGVHD. METHODS: Overall, 18 patients with oral manifestations
      of cGVHD were treated with either intraoral PUVA (n=7) or with topical
      corticosteroids (n=16). Four patients received intraoral PUVA after failure of
      topical steroids and one patient was treated with topical corticosteroids after
      failing treatment with intraoral PUVA. A glass fiber extension of an UVA source
      was used for manual intraoral application. Treatment with topical corticosteroids
      consisted of 0.1 mg/ml dexamethasone mouth wash four times a day in combination
      with antifungal prophylaxis. RESULTS: Four patients showed complete local
      response (CR) due to intraoral PUVA, two improved and one did not respond.
      Topical corticosteroids resulted in nine patients in CR, two improved and five
      did not respond. CONCLUSION: Intraoral PUVA as well as topical corticosteroids
      are effective in treatment of oral manifestations of oral GVHD with few side
      effects and improve quality of life in patients with cGVHD.

PMID- 15238097
TI  - Photochemotherapy inhibits angiogenesis and induces apoptosis of endothelial
      cells in vitro.
AB  - BACKGROUND: Photochemotherapy has long been used in the treatment of psoriasis;
      however, its mechanism has not been completely elucidated. Psoriasis is now
      regarded as an angiogenesis-related disease. Recent studies indicated that the
      inhibition of angiogenesis by photochemotherapy could be an underlying mechanism.
      It was found that photochemotherapy can downregulate the expression of angiogenic
      factors in keratinocytes. However, the direct effect of photochemotherapy on
      endothelial cells has not been studied. METHODS: In this study, we determined the
      effect of photochemotherapy on the proliferation of human microvascular
      endothelial cells through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay and cell cycle analysis. The migration assay
      and in vitro tube formation assay were used to investigate the migration
      properties and tube formation ability of human microvascular endothelial cells
      after psoralen plus UVA (PUVA) treatment. The apoptosis of endothelial cells
      elicited by photochemotherapy was also analyzed with fluorescence-activated cell
      sorting analysis (FACS). RESULTS: UVA (0.8-5.0 J/cm(2)) irradiation with the
      presence of 8-methoxypsoralen (8-MOP) (300 ng/ml) resulted in a dose-dependent
      reduction in the cell viabilities of endothelial cells. FACS data showed an
      accumulation of cells in G0/G1 phase of cell cycle and apoptotic features of cell
      death after UVA irradiation with psoralen. The migration properties and tube
      formation ability of endothelial cells were dramatically inhibited by
      photochemotherapy. CONCLUSION: Our results showed that photochemotherapy inhibits
      angiogenesis and induces apoptosis of human microvascular endothelial cells in
      vitro, which may be a possible mechanism of photochemotherapy in the treatment of
      psoriasis.

PMID- 15238098
TI  - Polymorphous light eruption (PLE) and a new potent antioxidant and UVA-protective
      formulation as prophylaxis.
AB  - BACKGROUND: Polymorphous light eruption (PLE) is the most common photodermatosis.
      While its etiology still remains elusive, pathogenesis seems to involve UVA
      induced oxidative stress and subsequent deregulation of antioxidative immune
      responses. Only few and often ineffective prophylactic and therapeutic measures
      exist to date. METHODS: In our randomized, double-blind, placebo-controlled
      clinical study, we compared the efficacy of a new topical formulation, consisting
      of 0.25%alpha-glucosylrutin (AGR) (a natural, modified flavonoid), 1% tocopheryl
      acetate (vitamin E) and a broad-spectrum, highly UVA-protective sunscreen (SPF
      15) in a hydrodispersion gel vehicle, to a sunscreen-only gel and vehicle. Thirty
      patients with a history of PLE were pretreated with either the above formulation,
      a similar preparation (with the same concentration for vitamin E and AGR, but a
      different UV filter system), placebo or a SPF 15 sunscreen-only gel, 30 min prior
      to daily photoprovocation with UVA irradiations of 60-100 J/cm(2) to 5 x 5 cm(2)
      areas on the upper arms. RESULTS: After 4 days, results revealed a statistically
      highly significant difference (P<0.001) between the antioxidant containing
      formulations and placebo, and sunscreen-only formulation, respectively, in
      experimentally eliciting PLE. While only one patient developed clinical signs of
      PLE with accompanying itch in the area treated with the new antioxidant UV
      protective gel formulation, 62.1% of the placebo-treated areas and 41.3% of the
      sunscreen-only treated areas showed mild to moderate signs of PLE. CONCLUSION:
      Combining a potent antioxidant with a broad-spectrum, highly UVA-protective
      sunscreen is far more effective in preventing PLE than sunscreen alone or placebo
      and should thus be employed as the prophylaxis of choice for PLE.

PMID- 15238099
TI  - No significant change of plasma beta-endorphin levels of psoriasis patients after
      synchronous balneophototherapy.
AB  - BACKGROUND/PURPOSE: Previous studies suggested that beta-endorphin has a
      pathogenic role in psoriasis: its increased plasma concentration may play a role
      in the neuroimmunological processes in the pathomechanism of the disease, and
      plasma beta-endorphin levels should reflect the changes in the patients' skin
      status. The purpose of this study was to investigate the changes of peripheral
      blood beta-endorphin levels in psoriatic patients in conjunction with changes in
      their skin symptoms after synchronous balneophototherapy. METHODS: With
      synchronous balneophototherapy, 12 patients with extended skin symptoms of
      psoriasis were treated. The therapy followed the Regensburg protocol, consisting
      of a basic course of 35 sessions. Patients' skin status was characterized by
      evaluating the Psoriasis Area and Severity Index score before and after the
      therapy course. Blood samples were taken before treatment, and 1 day after the
      last session, with symptom-free skin. Plasma beta-endorphin levels were measured
      by a specific radioimmunoassay developed by the authors. RESULTS: There was no
      significant change in plasma levels of beta-endorphin after clinical clearance of
      psoriatic skin symptoms. CONCLUSION: In this non-randomized, uncontrolled study
      no significant difference could be detected between plasma beta-endorphin levels
      before and after a basic course of synchronous balneophototherapy in patients
      with psoriasis. Although beta-endorphin has many neuroimmunological effects, the
      changes of its plasma level do not consistently reflect the skin status.
      Inflammation in psoriatic skin lesions is probably not mediated directly by
      circulating beta-endorphin.

PMID- 15238100
TI  - UVA-1 as a treatment for scleredema.
AB  - Scleredema is a rare disease that is difficult to treat. Many therapies have been
      tried with varied and somewhat inconsistent results. Here we report two cases of
      scleredema successfully treated with low-dose UVA-1.

PMID- 15238103
TI  - Determining the contribution of asphyxia to brain damage in the neonate.
AB  - Studies in the research laboratory have demonstrated the complex relationship
      between fetal and newborn asphyxia and brain damage, a balance between the
      degree, duration and nature of the asphyxia and the quality of the cardiovascular
      compensatory response. Clinical studies would support the contention that the
      human fetus and newborn behave in a similar manner. An accurate diagnosis of
      asphyxia requires a blood gas and acid base assessment. The clinical
      classification of fetal asphyxia is based on a measure of metabolic acidosis to
      confirm that fetal asphyxia has occurred and the expression of neonatal
      encephalopathy and other organ system complications to express the severity of
      the asphyxia. The prevalence of fetal asphyxia at delivery is at term, 25 per
      1000 live births of whom 15% are moderate or severe; and in the preterm, 73 per
      1000 live births of whom 50% are moderate or severe. It remains to be determined
      how often the asphyxia recognized at delivery may have been present before the
      onset of labor. There is a growing body of indirect and direct evidence to
      support the contention that antepartum fetal asphyxia is important in the
      occurrence of brain damage. Although much of the brain damage observed in the
      newborn reflects events that occurred before delivery, newborn asphyxia and
      hypotension, particularly in the preterm newborn, may contribute to the brain
      damage accounting for deficits in surviving children.

PMID- 15238105
TI  - Surgical repair of genital fistulae.
AB  - OBJECTIVE: Genital fistula is one of the serious childbirth injuries that can
      occur among women in the developing countries. Complex fistulae still represent a
      challenging management problem. We report our experience of managing genital
      fistulae at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. METHODS:
      Eighty-seven women with genital fistulae were managed between January 1988 and
      December 2002. Sixty-eight cases were urogenital and 19 were rectovaginal
      fistulae. Three women had concomitant urogenital and rectovaginal fistulae. The
      position of patients for surgery and the route of repair were individualized
      according to the appropriate access to the fistulae. RESULTS: Of the 68 cases of
      urogenital fistulae, 54 were successfully repaired at first attempt. Three
      patients were cured at second repair. A success rate of 83.8% was achieved. Four
      patient with ureterosigmoid anastomosis and seven patients who were lost to
      follow-up, were considered as failures. All of the 19 rectovaginal fistulae
      (100%) closed after single repair. CONCLUSION: With an experienced uro
      gynecologic team using conventional approach and meticulous repair, a high
      percentage of patients with genital fistulae can be rendered dry and continent.

PMID- 15238104
TI  - Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria
      for hereditary non-polyposis colorectal cancer (HNPCC), Amsterdam Criteria II.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome,
      is an autosomal dominantly inherited disorder of cancer susceptibility. Patients
      with HNPCC exhibit an increased risk for HNPCC-associated extracolonic tumors
      such as cancer of the endometrium. HNPCC is associated with germline mutations in
      DNA mismatch repair (MMR) genes: hMLH1, hMSH2 and hMSH6. Here, we describe two
      Japanese kindreds (0.5%) who met the new clinical criteria for HNPCC, Amsterdam
      criteria II, from among 375 endometrial cancer patients treated at Keio
      University Hospital from 1990 to 2002. From these results, it was found that
      female HNPCC patients comprised approximately 0.5% of all endometrial cancer
      patients. Decreased expression of two MMR gene protein products (hMLH1 and hMSH6)
      was confirmed immunohistochemically in these two endometrial tumors in HNPCC
      kindreds. This case report provides important information on Japanese HNPCC
      patients occurring endometrial cancer.

PMID- 15238106
TI  - Hormone replacement therapy and breast cancer risk in Kyushu University Hospital:
      supporting the Women's Health Initiative study.
AB  - AIM: The influence of hormone replacement therapy (HRT) on breast cancer has not
      been clarified in Japan, however the Women's Health Initiative (WHI) trial
      recently showed breast cancer risk according to use of estrogen plus progestin.
      We assessed retrospectively the incidence of breast cancer in postmenopausal
      women who received HRT at our outpatients clinic. METHODS: Among the patients
      registered at the postmenopausal clinic in Kyushu University Hospital from 1990
      to 2003, 917 women who received HRT (estrogen plus progestin, 507 patients;
      estrogen only, 410 patients) after informed consent were examined by mammography
      or breast ultrasound tomography. RESULTS: Breast cancer occurred in nine
      patients: five patients who received estrogen plus progestin and four who
      received estrogen only. Four of five the patients who used estrogen plus
      progestin received HRT for more than 5 years. CONCLUSION: Breast cancer risk in
      patients who used estrogen plus progestin for more than 5 years seemed to be
      higher than those who used it for less than 5 years. This tendency is similar to
      the results of the WHI. In addition, breast cancer incidence in patients treated
      with HRT in our clinic seemed to be higher than the incidence in average Japanese
      women. Therefore, patients need to be given sufficient information before
      undergoing HRT.

PMID- 15238107
TI  - Germ cell tumors of the ovary: a clinicopathologic study of 121 cases from Nepal.
AB  - BACKGROUND: Although many reports have been published about germ cell tumors of
      the ovary in developed countries, there has been no such documentation from
      Nepal. The retrospective study presented here reports the clinicopathologic
      profile of germ cell tumors of the ovary studied at B. P. Koirala Institute of
      Health Sciences, Dharan, Nepal. METHODS: A retrospective analysis of 121
      histopathologically proven cases of germ cell tumor of the ovary operated on at
      either our institute or somewhere else (but processed in our institute) from
      November 1995 to April 2001 (5.5 years) was done. Clinical data, histopathologic
      findings and complications were recorded. RESULTS: The prevalence of germ cell
      tumors was 43.36% (121/279) of all ovarian neoplasms. Patient age varied from 8
      to 65 years (median 31 years). Tumor occurrence was most frequent in patients
      aged 21-40 years. Only eight of 121 cases (6.61%) were malignant; the rest
      (93.39%) were mature teratomas. Of great interest was the unexpectedly high
      number of cases (47.93%) found in patients who were hill natives such as Rai and
      Gurung. Pain and abdominal fullness were common symptoms noted in 85.95% and
      79.31% of patients, respectively. Seventeen (14%) asymptomatic cases were found
      either on routine physical examination (12 cases) or during pregnancy (five
      cases). The left ovary was involved in 39.7% cases and the right in 35.5%.
      Bilateral involvement was seen in 24.8% of cases. Torsion was noted in 20.66% and
      was the most common complication. Of all the germ cell tumors 93.39% were cystic
      and only 6.61% were solid on gross appearance. There were three cases of
      monodermal benign teratoma, four cases of immature teratoma and one case of
      malignant transformation. CONCLUSION: Mature teratoma is the most common germ
      cell tumor and accounts for 40.50% of all ovarian neoplasms. The high prevalence
      of germ cell tumors of the ovary found among patients who were hill natives needs
      to be explored further.

PMID- 15238108
TI  - Study of psychosocial factors in Japanese patients suffering from menopausal
      disorders.
AB  - AIM: Psychosocial elements are often found in the background of patients with
      menopausal disorders, and counseling based on these elements is essential for
      effective treatment. In the study presented here an attempt was made to extract
      psychosocial factors from Japanese cases of menopausal disorders in which the
      patients exhibited the impact of psychiatric elements and required counseling.
      METHODS: A total of 97 cases in which the patients received counseling for the
      treatment of undefined complaints at our menopause clinic were analyzed. During
      counseling the patients were interviewed in regard to psychosocial factors and
      underwent psychological tests. RESULTS: About half of them were found to have
      experienced various interpersonal problems as well as health-related problems.
      The frequency of problems such as empty nest syndrome and loss of relatives or
      friends was relatively low. Work-related anxiety or hardships of life were
      frequent among the premenopausal patients, while concern about aging was often
      noted in their postmenopausal counterparts. The incidence of empty nest syndrome
      was high among the ovariectomized women, but worry about aging was frequently
      reported by those undergoing natural menopause. CONCLUSION: This preliminary
      study revealed that problems related to families and the patient's health account
      for a large part of the psychosocial factors affecting the development of
      menopausal disorders in Japan. Incorporating these findings into counseling will
      make outpatient clinics services more acceptable to such patients.

PMID- 15238109
TI  - Rapidly growing leiomyoma in a postmenopausal woman.
AB  - We present here a case of a rapidly growing leiomyoma occurring after menopause.
      The tumor weighed 4329 g, suggesting the rapid accumulation of 'hyaline
      fibrosis'. A small amount of proliferative activity was detected as evidenced by
      Ki-67 antigen immunoreactivity.

PMID- 15238110
TI  - Prospective study of glove perforation in obstetrical and gynecological
      operations: are we safe enough?
AB  - OBJECTIVES: To assess the glove perforation rate, efficacy of double gloving,
      effect of duration of surgery, expertise of surgeon and operative urgency on the
      glove perforation rate in obstetrical and gynecologic operations. METHODS: From
      February to September 2002, double glove protocol was made necessary for all
      major obstetrical and gynecologic procedures. The operating surgeon, first and
      second assistant were included in the study. Gloves damage was noted (overt by
      inspection, occult by hydroinsufflation technique). RESULTS: Of the 156
      procedures included in study, 32 procedures were performed (all emergency
      operations) single-gloved because surgeons found double gloving clumsy (56%),
      made it difficult to tie knots due to lack of dexterity (24%), or were too tight
      (20%). One thousand one hundred and twenty single gloves were examined after each
      procedure by hydroinsufflation. The overall perforation rate was 13.6% (single
      versus double outer gloves, 13.8% versus l3.2%, P > 0.05). Matching perforations
      were found in six cases (4.6%). Thus, the protection offered by double gloves was
      95.4% even if the outer gloves were perforated. Four inner gloves had preexisting
      perforations. Sixty unused gloves checked similarly revealed a perforation rate
      of 1.6%. Emergency cases had higher perforation rate compared to elective
      surgeries (16.6% versus 10.8%, P < 0.00 1). Surgeries lasting for more than 40
      min had a higher perforation rate compared to those finished in less than or
      equal to 40 min (18.6% versus 7.6%, P < 0.001). The middle finger of the left
      hand was the most commonly involved. The surgeon, first assistant and second
      assistant were involved in 73.6, 23.3 and 3.2% cases, respectively. CONCLUSION:
      Double gloving offers considerable protection against exposure to contaminants in
      the blood and body fluids of the patient and should be made routine, especially
      in developing countries where HIV, hepatitis B and C are widely prevalent. Double
      gloving should be made mandatory in emergency procedures, which have a higher
      perforation rate due to operative urgency, and gloves should be changed in
      operations lasting for more than 40 min to ensure integrity of barrier.

PMID- 15238111
TI  - Cervical varix accompanied by placenta previa in twin pregnancy.
AB  - BACKGROUND: Uterine cervical varix is a rare complication in pregnant women and
      can be the cause of obstetric hemorrhage in the vagina resulting in adverse
      events for both the mother and fetus. CASE: A 34-year-old Japanese woman was
      hospitalized at 18 weeks gestation because of cervical varix and placenta previa.
      Prophylactic tocolysis successfully controlled the obstetric hemorrhage. At 27
      weeks gestation, emergent cesarean section was performed because of intractable
      hemorrhage from the marginal placenta previa. Intraabdominal findings revealed no
      vascular malformation of the uterus, and the operation was performed
      uneventfully. A speculum examination of the vagina and cervix at 1 month
      postpartum were unremarkable. CONCLUSION: It is important to recognize the
      clinical features and available treatments for cervical varix.

PMID- 15238112
TI  - Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid
      to-late pregnancy loss.
AB  - AIM: Associations have been reported between antiphospholipid antibodies (aPL),
      mainly anticardiolipin antibodies (aCL) and/or the lupus anticoagulant, and
      recurrent pregnancy losses (RPL). However, relatively few studies describing
      antiphosphatidylethanolamine antibodies (aPE) have been reported. We describe the
      prevalence of aPL to both cardiolipin and phosphatidylethanolamine in patients
      with RPL. METHODS: Patients with recurrent early pregnancy losses (n = 145) and
      mid-to-late pregnancy loss(es) (n = 26) were screened for aPE and aCL. RESULTS:
      In patients with recurrent early pregnancy losses, prevalence of immunoglobulin G
      (IgG) aPE (17.9%, P = 0.001) and immunoglobulin M (IgM) aPE (12.4%, P = 0.01) was
      significantly higher than in the control group. In patients with mid-to-late
      pregnancy loss(es), prevalence of IgM aPE (19.2%, P = 0.008) and IgG aCL (23.1%,
      P = 0.02) was significantly higher than in the control group. CONCLUSION: Our
      data suggest that aPE may be a risk factor in patients with mid-to-late pregnancy
      loss(es) as well as recurrent early pregnancy losses.

PMID- 15238113
TI  - Fasting or two-hour postprandial plasma glucose levels in early months of
      pregnancy as screening tools for gestational diabetes mellitus developing in
      later months of pregnancy.
AB  - PURPOSE: The present study was done to find out whether the fasting or 2-hour
      postprandial plasma glucose (PPPG) levels in early months of pregnancy can be
      used as screening tools for gestational diabetes mellitus (GDM) developing in
      later months of pregnancy. BASIC PROCEDURE: Fasting and 2-hour PPPG levels were
      measured in the early months of pregnancy in 246 women attending the antenatal
      clinic of the author. All of the women underwent glucose challenge tests with 50
      grams of glucose at 24-28 weeks and if the value exceeded 140 mg%, a three-hour
      oral glucose tolerance test (OGTT) with 100 grams of glucose was performed to
      diagnose GDM. MAIN FINDINGS: The present study found that the incidence of GDM
      was 10.5% in the third trimester. Statistical analysis did not show any
      correlation between fasting and the PPPG values in the early months and GDM in
      later months of pregnancy. CONCLUSION: Fasting or PPPG values cannot be used as
      efficient screening tools for GDM developing in the later months of pregnancy.

PMID- 15238117
TI  - The relational core of nursing practice as partnership.
AB  - BACKGROUND: Consideration of the relational core of nursing has gained
      significance in today's health systems, where the work of nurses is dominated by
      technologically-driven, prescriptive, and outcome-oriented approaches. This has
      led to disregard for individual experiences of living life with diverse health
      conditions. AIM: The aim of this paper is to articulate the relational core of
      nursing practice as partnership. DISCUSSION: The relational core of nursing
      practice is explicated as a process of professional partnership, focusing on the
      evolving dialogue between nurse and patient. In partnership, the dialogue is
      open, caring, mutually responsive and non-directive. The nurse attends to that
      which is of concern to patients in relation to their health predicaments and the
      meaning in the health experience unfolds. Nurse and patient reach insight that
      represents more useful ways of comprehending and acting on their health
      predicaments. CONCLUSIONS: Partnership represents theoretically-driven practice
      that invites nurses to meet patients where they are in understanding their health
      predicaments and what can be done about them. As such, partnership strengthens
      the resolve of nurses to resist the pressures of contemporary health service
      delivery to provide a technical form of practice and it protects the relational
      core of a fully professional practice.

PMID- 15238120
TI  - Growth and development of children with congenital heart disease.
AB  - BACKGROUND: Children with congenital heart disease (CHD) commonly experience
      delayed growth. Because growth and development are closely related, both should
      be considered when a child's progress is examined. PURPOSE: This paper reports a
      study to evaluate and compare the growth and development of preschool children
      with CHD to those of normal preschool children. METHODS: The heights and weights
      of 42 preschool children with CHD and 116 normal preschool children were compared
      with standard growth curves. Differences in development of personal and social
      skills, fine motor skills and adaptability, language, and gross motor skills were
      evaluated. Developmental skills were assessed using the Denver Developmental
      Screening Test II. RESULTS: A significant difference was found in both body
      height (P < 0.05) and weight (P < 0.05) between the two groups. More preschoolers
      with congenital hear disease were below the 50th percentile in height (P < 0.05)
      and weight (P < 0.001). Preschoolers with CHD had more suspicious interpretations
      than non-CHD preschoolers, specifically in the language (P < 0.01) and gross
      motor sections (P < 0.001). Nevertheless, there were two items in the personal
      social section and one in the language section on which the children with heart
      disease passed in the range of 55.6-63.2%. Problems were encountered with the
      Denver II test because of differences in language, culture and childrearing
      methods between Taiwanese and Western societies. These cultural differences must
      be considered when the test is used to assess development. CONCLUSIONS: Learning
      about the growth and developmental differences between children with CHD and
      normal children may help parents of the former to detect problems associated with
      delayed growth and development earlier. These children and their families should
      have the opportunity to participate in a long-term, follow-up programme that
      provides information and encourages developmental progress. The results could
      serve as a reference for those in both clinical and community workers who provide
      nursing care to children with CHD.

PMID- 15238119
TI  - Patient safety and comfort during transfers in relation to nurses' work
      technique.
AB  - BACKGROUND: The work technique used by health care professionals in patient
      transfer tasks affects the musculoskeletal load on the professionals, but
      probably also the safety and well-being of patients being transferred; it is thus
      a matter of quality of care. AIMS: The aim of this paper is to report a study
      exploring the relations between the work technique of nurses in patient transfer
      tasks, and patients' perceptions of safety and comfort during the transfers.
      METHODS: The work technique used by 102 nurses at orthopaedic wards to perform
      two common patient transfers: one transfer higher up in bed and one from bed to
      wheelchair, were examined using video recordings and an observation instrument. A
      work technique score for each performed transfer was calculated, indicating the
      level of musculoskeletal safety for the nurse. Nurses assessed their own work
      technique and patients rated the perceived safety and comfort on bipolar scales
      directly after each transfer. RESULTS: Patients' perceptions of safety and
      comfort were positively correlated to the work technique score in both transfers.
      Patients felt safer and more comfortable during transfers performed with a safe
      technique, according to the work technique score, than during those performed
      with a poor technique. Patients' ratings of safety in the transfer from bed to
      wheelchair, and their ratings of comfort in both transfers, were positively
      correlated to nurses' assessments of their own work technique. However, the
      correlation coefficients were rather low. CONCLUSIONS: The results support the
      existence of a relationship between nurses' skills in patient transfers and
      quality of patient care.

PMID- 15238121
TI  - Decision-making models used by 'graduate nurses' managing patients' medications.
AB  - BACKGROUND: Nurses in a graduate programme in Australia are those who are in the
      first year of clinical practice following completion of a 3-year undergraduate
      nursing degree. When working in an acute care setting, they need to make complex
      and ever-changing decisions about patients' medications in a clinical environment
      affected by multifaceted, contextual issues. It is important that comprehensive
      information about graduate nurses' decision-making processes and the contextual
      influences affecting these processes are obtained in order to prepare them to
      meet patients' needs. AIM: The purpose of this paper is to report a study that
      sought to answer the following questions: What are the barriers that impede
      graduate nurses' clinical judgement in their medication management activities?
      How do contextual issues impact on graduate nurses' medication management
      activities? The decision-making models considered were: hypothetico-deductive
      reasoning, pattern recognition and intuition. METHODS: Twelve graduate nurses who
      were involved in direct patient care in medical and surgical wards of a
      metropolitan teaching hospital located in Melbourne, Australia participated in
      the study. Participant observations were conducted with the graduate nurses
      during a 2-hour period during the times when medications were being administered
      to patients. Graduate nurses were also interviewed to elicit further information
      about how they made decisions about patients' medications. RESULTS: The most
      common model used was hypothetico-deductive reasoning, followed by pattern
      recognition and then intuition. The study showed that graduate nurses had a good
      understanding of how physical assessment affected whether medications should be
      administered or not. When negotiating treatment options, graduate nurses readily
      consulted with more experienced nursing colleagues and doctors. STUDY
      LIMITATIONS: It is possible that graduate nurses demonstrated a raised awareness
      of managing patients' medications as a consequence of being observed.
      CONCLUSIONS: The complexity of the clinical practice setting means that graduate
      nurses need to adapt rapidly to make sound and appropriate decisions about
      patient care.

PMID- 15238122
TI  - Hope during the first months after acute spinal cord injury.
AB  - BACKGROUND: According to the general literature on hope, individuals who are
      hopeful live more positive lives than those who experience hopelessness. Hope has
      been defined as a positive orientation toward future improvements, and is
      associated with health and well-being. AIM: This paper reports a study that
      explored patients' experiences of hope following spinal cord injury. METHOD: Data
      were collected by personal interviews (n = 10) at a rehabilitation institution in
      Norway. A phenomenological-hermeneutic approach was used to extract the
      meaningful content of patients' experiences. The analysis was performed as a
      spiral process that included a reading to gain a sense of the whole, followed by
      identification of meaningful parts and a comprehensive and understandable
      interpretation of the whole. FINDINGS: Two themes emerged: 'images of the past
      and future', and 'balancing between inner emotional dichotomies' that were,
      mainly, related to experiences of courage/uncertainty and patience/restlessness.
      DISCUSSION: All participants experienced hope. The substance of hope--being able
      to walk again and hoping for recovery--was a universal experience among
      participants and was comprehended in terms of positive expectations. The process
      of hope involved continuous 'ups and downs'. Patients were in need of skilled
      nursing care to enable and foster hope during the first months following acute
      spinal cord injury. CONCLUSION: In conclusion, patients hoped for recovery and
      every improvement stimulated hope. The process of hope was future-oriented,
      characterized by dichotomies. Nurses need the skills to foster hope and enable
      recently injured patients to look beyond the immediate situation and direct their
      energies appropriately.

PMID- 15238123
TI  - Preventing sciatic nerve injury from intramuscular injections: literature review.
AB  - BACKGROUND: Injury to the sciatic nerve (SN) is a serious complication of
      intramuscular injection. AIM: The purpose of this paper was to identify factors
      associated with such iatrogenic injury in adults and measures that nurses may
      take to prevent it. METHOD: A review of the English language literature was
      undertaken to identify applicable research studies and determine the information
      that currently is being disseminated on relevant injection procedure. Legal
      databases were also searched for pertinent court decisions. DISCUSSION: The
      evidence is that injury to the SN is associated with use of the dorsogluteal (DG)
      site for injection. The choice of site for injection must be based on good
      clinical judgment, using the best evidence available and individualized
      assessment of the client. There is wide agreement in the literature that the
      ventrogluteal site is preferable. If the DG site is chosen, the nurse must have a
      full appreciation of the anatomy of the site and proximate anatomic structures,
      be able to accurately identify anatomic landmarks and site boundaries, and
      administer the injection with meticulous technique. Not only may SN injury
      resulting from erroneous injection cause client discomfort, morbidity and lasting
      disability, but it also provides the basis for nursing negligence suits.
      CONCLUSION: The research base for intramuscular injection is limited. Studies on
      various aspects of the procedure need to be carried out to provide support for
      clinical guidelines.

PMID- 15238124
TI  - How many do I need? Basic principles of sample size estimation.
AB  - BACKGROUND: In conducting randomized trials, formal estimations of sample size
      are required to ensure that the probability of missing an important difference is
      small, to reduce unnecessary cost and to reduce wastage. Nevertheless, this
      aspect of research design often causes confusion for the novice researcher. AIM:
      This paper attempts to demystify the process of sample size estimation by
      explaining some of the basic concepts and issues to consider in determining
      appropriate sample sizes. METHOD: Using a hypothetical two group, randomized
      trial as an example, we examine each of the basic issues that require
      consideration in estimating appropriate sample sizes. Issues discussed include:
      the ethics of randomized trials, the randomized trial, the null hypothesis,
      effect size, probability, significance level and type I error, and power and type
      II error. The paper concludes with examples of sample size estimations with
      varying effect size, power and alpha levels. CONCLUSION: Health care researchers
      should carefully consider each of the aspects inherent in sample size
      estimations. Such consideration is essential if care is to be based on sound
      evidence, which has been collected with due consideration of resource use,
      clinically important differences and the need to avoid, as far as possible, types
      I and II errors. If the techniques they employ are not appropriate, researchers
      run the risk of misinterpreting findings due to inappropriate, unrepresentative
      and biased samples.

PMID- 15238125
TI  - A theoretical model of job retention for home health care nurses.
AB  - BACKGROUND: Predicted severe nursing shortages and an increasing demand for home
      health care services have made the retention of experienced, qualified nursing
      staff a priority for health care organizations. AIMS: The purpose of this paper
      is to describe a theoretical model of job retention for home health care nurses.
      METHODS: The theoretical model is an integration of the findings of empirical
      research related to intent to stay and retention, components of Neal's theory of
      home health care nursing practice and findings from earlier work to develop an
      instrument to measure home health care nurses' job satisfaction. DISCUSSION: The
      theoretical model identifies antecedents to job satisfaction of home health care
      nurses. The antecedents are intrinsic and extrinsic job characteristics. The
      model also proposes that job satisfaction is directly related to retention and
      indirectly related to retention though intent to stay. Individual nurse
      characteristics are indirectly related to retention through intent to stay. The
      individual characteristic of tenure is indirectly related to retention through
      autonomy, as an intrinsic characteristic of job satisfaction, and intent to stay.
      CONCLUSIONS: The proposed model can be used to guide research that explores gaps
      in knowledge about intent to stay and retention among home health care nurses.

PMID- 15238126
TI  - Health promotion and health education: advancing the concepts.
AB  - BACKGROUND: Health education and health promotion activities are a fundamental
      requirement for all health professionals. These two paradigms are closely related
      but are not inter-dependent. Despite this, it is known that many nurses confuse
      the terms and use them interchangeably. With this in mind, it is necessary to re
      conceptualize the terms in an attempt to bring them to a current form of
      'maturity'. AIM: The aim of the paper is to provide an up-to-date analysis of
      health promotion and health education that serves as a conceptual and operational
      foundation for clinicians and researchers. METHOD: A concept analysis following
      the criterion-based methods described by Morse and her colleagues was applied to
      the terms health education and health promotion, using generic and nursing
      related literature. RESULTS: The conceptual literature on health education is
      consistent between generic and nursing-related sources. On the contrary, earlier
      nursing literature on health promotion is now at odds with more recent socio
      political and community action models of health promotion, in that it focuses on
      individualistic and behavioural forms of 'health promotion'. A significant
      proportion of later nursing-related literature, however, suggests a maturing of
      the concept that brings it further in line with a socio-political health
      promotion agenda. CONCLUSION: While the theoretical and conceptual literature
      surrounding health education has remained relatively constant and unchanged over
      the last decade or so, the same cannot be said for the health promotion
      literature. The evolving dominance of socio-political action in health promotion
      has overtaken individualistic and behaviourally-related forms. While the recent
      nursing literature addresses and acknowledges the place of socio-political
      activity as the mainstay of health promotion interventions, this is largely from
      a theoretical stance and is not applied in practice.

PMID- 15238127
TI  - Men nurses: a historical and feminist perspective.
AB  - BACKGROUND: The history of nursing is almost exclusively a history of women's
      accomplishments despite the fact that, as early as the fourth and fifth
      centuries, men have worked as nurses. This perpetuates the notion of men nurses
      as anomalies. It also provides insight into the gendered nature of nursing and
      nurses' work within patriarchal culture. AIM: This paper examines the history of
      men in nursing in Canada, Britain and the United States of America, and offer
      insights into the ways in which gender relations and the ideological designation
      of nursing as women's work have excluded, limited and, conversely, advanced the
      careers of men nurses. METHOD: A search of the literature was carried out using
      CINAHL, PubMed and Sociological Abstracts databases. Search words included: male
      nurses, history, nursing, Canada, Britain, United Kingdom and USA. DISCUSSION:
      Men's participation in nursing reveals that prevailing definitions of masculinity
      have acted as a powerful barrier to men crossing the gender divide and entering
      the profession. At extraordinary times such as war and acute nursing shortages,
      gender boundaries are negotiable. For those men who have crossed over into
      nursing, a gendered division of labour is evidenced by men nurses' long-standing
      association with mental health nursing and, more recently, with their
      disproportionate attainment of masculine-congruent leadership and specialty
      positions. CONCLUSION: Failure to recognize men's participation in nursing leaves
      men nurses with little information about their professional background and
      historical position. It also maintains the invisibility of gender relations that
      have shaped the experience of men and women nurses alike. Such relations,
      understood within their broader social context, remain poorly understood and
      hence uninterrupted, to the detriment of nurses and the profession of nursing.

PMID- 15238128
TI  - Using a Nursing Minimum Data Set with older patients with dementia in an acute
      care setting.
AB  - BACKGROUND: Many older people with dementia are admitted to acute care settings
      suffering from comorbidities. These and their treatments can lead to confusion in
      these patients, adding to their existing cognitive deficits, and this may not be
      recognized by care staff. The care of such patients is complex and requires
      multidisciplinary team input. The purposes of the Nursing Minimum Data Set are to
      describe the nursing care of patients in a variety of settings and to establish
      comparability of nursing data across clinical populations, settings and time.
      AIMS: This paper reports a study to describe the characteristics of hospitalized
      older patients with dementia and nursing diagnoses and nursing interventions for
      these patients, and to identify trends in the nursing care provided over a 3-year
      period using a Nursing Minimum Data Set from a community hospital in the United
      States of America. METHODS: Secondary data analysis was conducted in 2000 on a
      large clinical discharge data set containing Nursing Minimum Data Set elements.
      The sample included 597 elders with dementia among a total of 7772 older patients
      who were discharged between 1996 and 1998. RESULTS: The most common comorbidity
      was hypertension (n = 123, 21%), followed by cardiac dysrhythmias (n = 80, 13%).
      The most frequent nursing diagnoses were altered health maintenance (n = 419,
      84%), knowledge deficit (n = 357, 71%), potential for injury (n = 242, 48%),
      potential for infection (n = 230, 46%), pain (n = 184, 37%), impaired physical
      mobility (n = 169, 34%), and altered thought process (n = 144, 29%). The most
      frequent interventions were discharge planning (n = 340, 68%), surveillance
      safety (n = 195, 39%), fall prevention (n = 175, 35%), teaching: disease process
      (n = 166, 33%), learning facilitation (n = 148, 30%), and infection protection (n
      = 147, 29%). CONCLUSIONS: The results provide a description of nursing diagnoses
      and interventions for elders with dementia in an acute care setting using the
      Nursing Minimum Data Set framework. They identify the need to develop staff
      education programmes for individualized care of older patients with dementia. In
      addition, they support the need for continued work on linkage of the nursing care
      elements of the Nursing Minimum Data Set, including nursing diagnoses, nursing
      interventions, and nursing-sensitive outcomes.

PMID- 15238129
TI  - A response to: 'Infant feeding attitudes of expectant parents: breastfeeding and
      formula feeding' by I. Shaker, J. A. Scott and M. Reid (2004) Journal of Advanced
      Nursing 45 (3), 260-268, from Janel Pozo.

PMID- 15238131
TI  - Novel AIDS treatment programme for health care workers in Zambia.

PMID- 15238135
TI  - Iliac giant pseudotumour in a haemophiliac patient.

PMID- 15238136
TI  - Pulmonary calcinosis in adult T-cell leukaemia.

PMID- 15238137
TI  - Toward more effective antifungal therapy: the prospects of combination therapy.
AB  - The availability of new antifungal agents with unique mechanisms of action and
      improved tolerability has widened the possibilities for the use of combination
      antifungal therapy for difficult-to-treat opportunistic mycoses. However, the use
      of this therapy is largely governed by empiricism, especially in patients with
      invasive mould infections, for whom there is a tremendous need to improve
      outcomes. Because of the difficulties associated with the design and conduct of
      clinical trials of combination antifungal therapy for opportunistic mycoses, the
      majority of the studies evaluating antifungal combinations are still performed in
      the laboratory or using animal models of infection. However, the methods used to
      assess combined antifungal effects in vitro and in animals are poorly
      standardized, and there is little evidence that data generated from these studies
      can be translated in treating human mycotic infections. Despite the empiricism of
      combination antifungal therapy, certain principles help guide the use and study
      of these regimens.

PMID- 15238138
TI  - Fanconi anaemia and leukaemia - clinical and molecular aspects.
AB  - Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder,
      which is characterized by congenital abnormalities, defective haemopoiesis and a
      high risk of developing acute myeloid leukaemia and certain solid tumours. It can
      be caused by mutations in at least eight different genes. Molecular studies have
      established that a common pathway exists, both between the FA proteins and other
      proteins involved in DNA damage repair such as NBS1, ATM, BRCA1 and BRCA2. This
      review summarizes the general clinical and specific haematological features and
      the current management of FA. Recent molecular advances will also be discussed in
      the context of the cellular and clinical FA phenotype, with particular emphasis
      on the haematological aspects of the condition.

PMID- 15238139
TI  - Myeloma cells can directly contribute to the pool of RANKL in bone bypassing the
      classic stromal and osteoblast pathway of osteoclast stimulation.
AB  - Summary The ratio of osteoprotegerin [OPG, tumour necrosis factor receptor
      superfamily, member 11b (TNFRSF11B)] to receptor activator of nuclear factor
      kappaB ligand [RANKL, tumour necrosis factor (ligand) superfamily, member 11
      (TNFSF11)] in bone is critical for the regulation of bone remodelling. Myeloma
      cells can home to bone, triggering increased RANKL and decreased OPG expression
      by stromal cells, leading to osteolysis. Whether myeloma cells contribute
      directly to the pool of RANKL or OPG in bone has been contentious. Here we
      provide evidence of RANKL expression by reverse transcription polymerase chain
      reaction and in situ hybridization, demonstrating transcripts encoding both the
      membrane-bound and secreted forms of RANKL in five human multiple myeloma cell
      lines (LP-1, NCI-H929, OPM-2, RPMI8226, U266) and myeloma cells purified from
      bone marrow aspirates of myeloma patients. We demonstrated that RANKL encoding
      mRNAs are translated to protein by antibody detection of RANKL. In vitro assays
      showed that myeloma cells induced bone marrow derived mononuclear cells to
      differentiate into adherent tartrate-resistant acid phosphatase positive
      multinucleated cells, indicative of the formation of functional osteoclasts. This
      differentiation could also be achieved with passaged myeloma media alone,
      implicating secreted products. Finally, we provide evidence that the
      differentiation observed is at least in part the result of myeloma cell
      expression of RANKL. We therefore conclude that myeloma cells can directly
      contribute to the pool of RANKL in bone.

PMID- 15238140
TI  - Ocular presentation of primary central nervous system lymphoma: diagnosis and
      treatment.
AB  - Primary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of
      primary central nervous system lymphoma (PCNSL) that often progresses to the
      brain and meninges; frequently it is misdiagnosed until central nervous system
      (CNS) lymphoma develops. The optimal treatment has not yet been identified. We
      retrospectively reviewed the course and the treatment of POL in 31 patients.
      Seventeen patients were treated for isolated POL (group A) and 14 were treated
      only after CNS disease was diagnosed (group B). The treatment in both groups
      consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT
      alone. In group A, nine patients (53%) developed CNS progression and five (29%)
      had ocular recurrence. In group B, seven (50%) had CNS progression and three
      (21%) ocular relapse. To control for diagnostic lead time, median survival was
      calculated from initial ocular symptoms and was 60 months in group A and 35
      months in group B (P < 0.05). Ocular lymphoma responds to a variety of therapies
      but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to
      prevent CNS progression. Patients whose ocular disease was identified and treated
      before CNS progression had a significantly improved survival.

PMID- 15238141
TI  - Haematogones in the peripheral blood of adults: a four-colour flow cytometry
      study of 102 patients.
AB  - Haematogones have been extensively characterized in bone marrow, but not in the
      peripheral blood (PB). We studied 102 PB samples from adult patients with a
      sensitive flow cytometry method. Sixty-six of 102 samples (65%) contained
      detectable haematogones, ranging from 0.01% to 1.3% of white blood cells (median
      0.06%, mean 0.13%). Of 66 cases with complete blood count data, 51 had absolute
      haematogone counts of 0.00037-0.105 x 10(9)/l (median 0.0054 x 10(9)/l, mean
      0.012 x 10(9)/l). PB haematogones belonged exclusively to the most mature
      maturational stage. These findings have implications for PB analysis of minimal
      residual disease in acute lymphoblastic leukaemia and follicular lymphoma.

PMID- 15238142
TI  - Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving
      protease.
AB  - ADAMTS-13, the metalloprotease that disposes physiologically of the most
      thrombogenic multimers of von Willebrand factor (VWF), tends to be low in plasma
      when VWF is high. We evaluated the behaviour of these two proteins in naturally
      occurring, experimental and clinical situations associated with VWF levels
      spanning from undetectable to supranormal. ADAMTS-13 was approximately 10% higher
      (and VWF 35% lower) in 65 healthy individuals of blood group O than in 65
      individuals of groups A, B and AB. Thirty-three patients with type 3 von
      Willebrand disease (VWD) with undetectable plasma VWF had approximately 35%
      higher levels of ADAMTS-13 than a comparable group of healthy individuals with
      normal VWF. When VWF was raised to supranormal levels by desmopressin (DDAVP) in
      10 healthy volunteers, ADAMTS-13 decreased by approximately 20%, with no change
      of the protease in three patients with severe VWD who had no post-DDAVP VWF rise.
      When VWF was raised from very low to normal levels by the infusion of VWF
      containing plasma concentrates in four patients with type 3 VWD and one with type
      1 VWD plasma, ADAMTS-13 decreased in parallel. These data show that throughout a
      large spectrum of plasma VWF levels there is a negative association between this
      protein and the activity of its major cleaving protease.

PMID- 15238143
TI  - Identification of protein Salpha gene mutations including four novel mutations in
      eight unrelated patients with protein S deficiency.
AB  - Eight distinct and potentially causative mutations were identified in eight
      unrelated Japanese patients with protein S (PS) deficiency, by direct DNA
      sequencing of the protein Salpha (PSalpha) gene-specific polymerase chain
      reaction products of all 15 exons and exon/intron boundaries. There were five
      missense mutations, including two novel mutations (Cys80Tyr and Arg314His), and
      three showed a major impact on the expected gene products: novel mutations of a 5
      bp deletion (delCTCTG887:Cys206Stop) and a nonsense mutation (Glu208Stop), as
      well as a previously reported splice site (exon 10 +5 A-->G) mutation. One of the
      patients showed compound heterozygosity for delCTCTG887 and 732A-->G.
      Investigation for the cosegregation state of these two mutations with PS
      deficiency in the patient's family suggested that the delCTCTG887 mutation was
      responsible for the abnormal phenotype and that the 732A-->G (Lys155Glu) mutation
      did not appear to play a key role. However, we also identified the same 732A-->G
      (Lys155Glu) mutation in an unrelated patient with apparent PS deficiency with
      severe pulmonary embolism, and found that this mutation seemed to cosegregate
      with a PS-deficient state in her family members. These data implied that unknown
      factor(s) other than the 732A-->G mutation itself might influence phenotypic
      expression of PS status in different individuals.

PMID- 15238144
TI  - 6,7-Dihydroxy-3-phenylcoumarin inhibits thromboplastin induced disseminated
      intravascular coagulation.
AB  - 6,7-Dihydroxy-3-phenylcoumarin (DHPC) was tested to determine whether it had any
      effect on vitamin K inhibition, by investigating the prothrombin time (PT),
      activated partial thromboplastin time (APTT), fibrinogen level and platelet
      count. The anticoagulant and antithrombotic effects of DHPC were compared with
      those of warfarin by conducting a 4 h acute trial on thromboplastin-induced
      disseminated intravascular coagulation (DIC), investigating various haemostatic
      and antioxidant system parameters and performing a haemogram. Of most
      significance was that in the 5-d DHPC trial on healthy controls, PT, APTT,
      fibrinogen, platelet count remained within normal levels. In the 4-h DIC trial,
      both DHPC (0.025 mg/kg, i.v.) and warfarin (0.25 mg/kg, i.v.) significantly
      inhibited DIC, by reducing the PT, APTT, and fibrin degradation products and
      increasing fibrinogen levels and platelet count. In the DIC drug groups, lipid
      peroxidation significantly increased only in the warfarin group and glutathione
      significantly increased only in the DHPC group. However leucocyte count was
      significantly higher in the DHPC than the warfarin group. Further investigation
      is required for why DHPC is effective on the parameters investigated, at doses
      one-tenth of those of warfarin.

PMID- 15238145
TI  - Impact of pre-analytical handling on bone marrow mRNA gene expression.
AB  - Large clinical trials on leukaemia, require the transport of bone marrow (BM)
      from participating clinics to central diagnostic laboratories. We have
      investigated the impact of RNA extraction protocols and time delays between
      sample aspiration and RNA extraction on RNA quality and gene expression profiles.
      Intact RNA can be extracted from BM samples stored at room temperature for up to
      48 h. Gene expression analyses using Affymetrix U95Av2 GeneChips and a custom
      designed cDNA array in parallel showed that even short-term storage of BM has
      dramatic effects on mRNA expression of individual transcripts. Many probe
      sets/genes showed either reproducible deregulation (18.8%, analysis of variance
      <0.05), or inconsistent expression that differed from patient to patient (38.4%).
      Moderate alterations were observed in 42.8% genes, with a maximum fold change
      <2.0 in all experiments and at all time points. These profound effects complicate
      the use of unstabilized, shipped BM samples for gene expression analyses. The
      comparison of a variety of RNA stabilization reagents (e.g. PAXgene) resulted in
      partial conservation of the mRNA expression patterns. Immediate density
      centrifugation or erythrocyte lysis and freezing at -80 degrees C represent
      simple procedures that reliably preserved mRNA gene expression patterns in BM.

PMID- 15238146
TI  - Synthesis of osteoprotegerin and RANKL by megakaryocytes is modulated by
      oestrogen.
AB  - To investigate the mechanisms by which megakaryocytes (MKs) may influence bone
      remodelling, CD34(+) cells were cultured for 6, 9 and 12 d with or without 17beta
      oestradiol (E) and immunolocalized for osteoprotegerin (OPG), receptor activator
      of nuclear factor (NF)-kappaB ligand (RANKL) and CD61. Specific protein
      expression was measured quantitatively by image analysis. Fluorescence-based
      immunocytochemistry was used to co-localize OPG and RANKL with CD61. OPG and
      RANKL mRNA was assessed in CD61(+) cells with or without E at 24 and 48 h. At 6
      d, OPG and RANKL expression was unchanged by E treatment. At 9 d, the E-treated
      cultures with maturing MKs showed a 1.72-fold (P < 0.01) increase in OPG
      expression and a 1.8-fold (P < 0.01) reduction in RANKL. Maximal OPG expression
      was seen at 12 d with a threefold induction of expression (P < 0.001), whilst
      RANKL levels were further suppressed by 2.3-fold compared with controls (P <
      0.001). CD61 co-localized with OPG and RANKL. mRNA data were consistent with that
      of protein, with a 90-fold induction in OPG expression and a 34-fold suppression
      of RANKL expression by E (P < 0.001). Thus, E stimulates megakaryocytopoiesis and
      modulates OPG and RANKL expression, providing evidence that MKs may play a role
      in bone remodelling and, in particular, in E-induced changes in
      osteoclastogenesis and bone resorption.

PMID- 15238147
TI  - Neutrophil CD177 (NB1 gp, HNA-2a) expression is increased in severe bacterial
      infections and polycythaemia vera.
AB  - The NB1 glycoprotein (CD177, HNA-2a antigen) is exclusively expressed on human
      neutrophils. As the clinical significance of CD177 expression is unknown, we
      investigated its expression in healthy individuals before and after stimulation
      with granulocyte colony-stimulating factor (G-CSF), in patients with rheumatoid
      arthritis, viral hepatitis, severe bacterial infections and polycythaemia vera.
      Expression was quantitatively determined by flow cytometry and by real time
      polymerase chain reaction. Only G-CSF-stimulated individuals and patients with
      severe bacterial infections and polycythaemia showed a significantly (P < 0.001)
      increased CD177 expression compared with healthy individuals, indicating that
      neutrophil CD177 expression can increase significantly in certain clinical
      conditions.

PMID- 15238148
TI  - Direct interaction between the Lu/B-CAM adhesion glycoproteins and erythroid
      spectrin.
AB  - Lutheran (Lu) and Lu(v13), two glycoprotein (gp) isoforms belonging to the
      immunoglobulin superfamily, represent adhesion molecules that act as erythrocyte
      receptors for laminin 10/11. These two gps, which differ only by the length of
      their cytoplasmic tail, carry both Lu blood group and Basal Cell Adhesion
      Molecule (B-CAM) antigens. Here, analysis of the Triton extractability of
      recombinant Lu and Lu(v13) gps in K562 transfected cells showed that both gps
      were mainly associated with the detergent-insoluble material. Patching
      experiments using Cholera Toxin subunit B indicated that Lu gps were not
      localized in lipid rafts. Glutathione-S-transferase capture assays showed that
      the cytoplasmic domain of Lu and Lu(v13) bound to erythroid spectrin, present in
      a low ionic strength extract from red cell ghosts. Direct interaction with
      spectrin was confirmed by plasmon resonance assays. Site-directed mutagenesis
      mapped a major interaction site with spectrin to the RK573-574 motif, located on
      the cytoplasmic tail of Lu gp, in close vicinity to the inner leaflet of the
      membrane lipid bilayer. The two Lu adhesion gps represent the first example of a
      direct link between transmembrane proteins and spectrin in red blood cells. Since
      Lu gps are low abundant proteins, we speculate that their interaction with
      spectrin might be critical for signalling and receptor function rather than for
      participating in the linkage of the lipid bilayer to the red cell skeleton.

PMID- 15238149
TI  - Molecular basis of Japanese variants of pyrimidine 5'-nucleotidase deficiency.
AB  - The type-I isoform of pyrimidine 5'-nucleotidase (P5N-I) has an important role in
      the catabolism of pyrimidine mononucleotides during erythroid maturation. Two
      alternatively spliced forms of P5N-I mRNA have been identified, and we found
      another alternatively spliced form in reticulocytes, which included an additional
      87-bp sequence. The sequence is located 6.2-kb downstream of the exon 2 and 2.7
      kb upstream of the exon 3 sequence; consequently, the P5N-I gene encodes 11
      exons, which span approximately 48 kb. We identified five novel mutations in nine
      families with P5N-I deficiency: two missense mutations (425C, 721C), one splice
      mutation (339C), one 1-bp insertion (251-insA-252) and one 9-bp deletion (del 192
      200). All patients were homozygous for each mutation. The mutant P5N-I with 721C
      (G241R) had lower affinity for cytidine monophosphate, suggesting that Gly241 is
      important for substrate binding. Haplotype analysis showed that 721C, which had
      been identified in five unrelated families, was a founder mutation. The mutant
      P5N was then expressed in Cos-7. The degradation of P5N with 425C (L142P) was
      significantly faster than a wild-type control, and proteasome inhibitors restored
      the stability of L142P. These data suggest that L142P increases susceptibility to
      the degradation by the ubiquitin-proteasome pathway.

PMID- 15238150
TI  - Dehydrated hereditary stomatocytosis is associated with neonatal hepatitis.
AB  - Dehydrated hereditary stomatocytosis (DHSt) is an inherited haemolytic anaemia
      associated with increased red cell membrane permeability to Na(+) and K(+). It is
      increasingly recognized that a syndrome of self-limiting perinatal ascites can
      accompany the haemolysis. The cause of the perinatal ascites is unknown, and it
      has been argued that this could be due to cardiovascular, hepatic or lymphatic
      problems. We describe the case of a 16-year-old girl who presented neonatally
      with abnormal liver function tests and ascites. She was extensively investigated
      at that time. A liver biopsy showed hepatitis and fatty changes. Her ascites
      resolved within 6 months. At the age of 15 years, she developed an episode of
      acute haemolysis and was re-investigated. A diagnosis of DHSt was made.
      Pseudohyperkalaemia, due to ex vivo loss of K(+) from red cells, was present.
      This study confirms the previously noted association of DHSt, pseudohyperkalaemia
      and perinatal ascites, and suggests that the latter is of predominantly hepatic
      origin.

PMID- 15238151
TI  - Applications of murine and humanized chimaeric monoclonal antibodies for red cell
      phenotyping.
AB  - The limited supply of reagent human polyclonal antibodies to high prevalence
      antigens, like Js(b), is driving the search for alternative reagents. Murine
      immunoglobulin G (IgG) monoclonal antibodies (Mabs) and their humanized chimaeric
      IgM isoforms can now be used for typing patients and screening donors. Antigen
      typing of red blood cells (RBC) with a positive direct antiglobulin test (DAT) is
      also possible using these antibodies. Blood from patients with sickle cell
      disease and African donors were tested with reagent anti-Js(b), murine Mab IgG
      anti-Js(b) [murine immunochemistry monoclonal antibody-8 (MIMA-8)], and humanized
      chimaeric IgM anti-Js(b) [human immunochemistry monoclonal antibody-8 (HIMA-8)]
      by haemagglutination and gel cards. RBC samples that were DAT positive were used
      to evaluate the humanized chimaeric IgM monoclonal anti-Fy(a) (HIMA-19). RBC
      samples (n = 243) of known Js(b) type were tested in parallel with MIMA-8 and
      reagent anti-Js(b), and 132 samples were tested with MIMA-8 in gel cards and HIMA
      8 by direct tube testing. No discrepant results were obtained. DAT-positive RBC
      samples (n = 27) were correctly phenotyped using HIMA-19. We conclude that MIMA-8
      is suitable for screening donors and typing patient RBCs. Testing MIMA-8 with gel
      cards containing anti-mouse IgG enables the screening of donors by automated
      methods. Humanized chimaeric IgM anti-Js(b) and anti-Fy(a) are suitable as typing
      reagents by direct agglutination methods.

PMID- 15238152
TI  - Medical nemesis and childhood idiopathic thrombocytopenic purpura.

PMID- 15238155
TI  - International questionnaire postal response rate: an experiment comparing no
      return postage to provision of International Postage Vouchers--"Coupon-Reponse
      International".
AB  - BACKGROUND: Previous studies of methods to increase response rates on
      international postal surveys did not include providing return postage. We
      provided International Postage Vouchers--"Coupon-Reponse International" to cover
      this. The objective of this study was to see if these International Postage
      Vouchers had an effect on response rates. METHODS: Between-groups, randomized,
      after-only. RESULTS: There was no difference in response rates between the group
      that received International Postage Vouchers and the group that did not. (p =
      0.23). CONCLUSION: International Postage Vouchers--"Coupon-Reponse International"
      have no effect on response rates for international postal surveys.

PMID- 15238156
TI  - Protective effect of Arque-Ajeeb on acute experimental diarrhoea in rats.
AB  - BACKGROUND: Diarrhoea is a major health problem for children worldwide,
      accounting for 5-8 million deaths each year. Arque-Ajeeb (AA) is a compound
      formulation of Unani medicine. It is reputed for its beneficial effects in the
      treatment of diarrhoea and cholera, but the claim of its efficacy is yet to be
      tested. Therefore the present study has been planned to investigate the real
      efficacy of this drug in rats. METHODS: The effect of Arque-Ajeeb was
      investigated for antidiarrhoeal activity against charcoal-induced gut transit,
      serotonin-induced diarrhoea and PGE2-induced small intestine enteropooling in
      rats. The control, standard and test groups of experimental animals were
      administered with normal saline (p.o.), diphenoxylate hydrochloride (5 mg/kg,
      p.o.) and Arque-Ajeeb (0.07 ml and 0.14 ml/kg, p.o.) respectively except the
      control group of PGE2-induced small intestine enteropooling which received only
      5% ethanol in normal saline (i.p.). Charcoal (10 ml/kg, p.o.) and serotonin (600
      micrograms/kg, i.p.) were administered after 30 min, while PGE2 (100
      micrograms/kg, p.o.) was administered immediately afterwards. The distance
      traveled by charcoal in small intestine was measured after 15 and 30 min of
      charcoal administration, diarrhoea was observed every 30-min for six hour after
      serotonin administration and the volume of intestinal fluid was measured after 30
      min of PGE2 administration. RESULTS: Arque-Ajeeb (0.07 ml and 0.14 ml/kg)
      significantly inhibited the frequency of defaecation and decreased the propulsion
      of charcoal meal through the gastrointestinal tract, reduced the wetness of
      faecal droppings in serotonin-induced diarrhoea and also reduced the PGE2-induced
      small intestine enteropooling. CONCLUSION: Arque-Ajeeb may have potential to
      reduce the diarrhoea in rats. Thus the drug may prove to be an alternate remedy
      in diarrhoea.

PMID- 15238157
TI  - Synaptotagmin gene content of the sequenced genomes.
AB  - BACKGROUND: Synaptotagmins exist as a large gene family in mammals. There is much
      interest in the function of certain family members which act crucially in the
      regulated synaptic vesicle exocytosis required for efficient neurotransmission.
      Knowledge of the functions of other family members is relatively poor and the
      presence of Synaptotagmin genes in plants indicates a role for the family as a
      whole which is wider than neurotransmission. Identification of the Synaptotagmin
      genes within completely sequenced genomes can provide the entire Synaptotagmin
      gene complement of each sequenced organism. Defining the detailed structures of
      all the Synaptotagmin genes and their encoded products can provide a useful
      resource for functional studies and a deeper understanding of the evolution of
      the gene family. The current rapid increase in the number of sequenced genomes
      from different branches of the tree of life, together with the public deposition
      of evolutionarily diverse transcript sequences make such studies worthwhile.
      RESULTS: I have compiled a detailed list of the Synaptotagmin genes of
      Caenorhabditis, Anopheles, Drosophila, Ciona, Danio, Fugu, Mus, Homo, Arabidopsis
      and Oryza by examining genomic and transcript sequences from public sequence
      databases together with some transcript sequences obtained by cDNA library
      screening and RT-PCR. I have compared all of the genes and investigated the
      relationship between plant Synaptotagmins and their non-Synaptotagmin
      counterparts. CONCLUSIONS: I have identified and compared 98 Synaptotagmin genes
      from 10 sequenced genomes. Detailed comparison of transcript sequences reveals
      abundant and complex variation in Synaptotagmin gene expression and indicates the
      presence of Synaptotagmin genes in all animals and land plants. Amino acid
      sequence comparisons indicate patterns of conservation and diversity in function.
      Phylogenetic analysis shows the origin of Synaptotagmins in multicellular
      eukaryotes and their great diversification in animals. Synaptotagmins occur in
      land plants and animals in combinations of 4-16 in different species. The
      detailed delineation of the Synaptotagmin genes presented here, will allow easier
      identification of Synaptotagmins in future. Since the functional roles of many of
      these genes are unknown, this gene collection provides a useful resource for
      future studies.

PMID- 15238158
TI  - Biologically meaningful expression profiling across species using heterologous
      hybridization to a cDNA microarray.
AB  - BACKGROUND: Unravelling the path from genotype to phenotype, as it is influenced
      by an organism's environment, is one of the central goals in biology. Gene
      expression profiling by means of microarrays has become very prominent in this
      endeavour, although resources exist only for relatively few model systems. As
      genomics has matured into a comparative research program, expression profiling
      now also provides a powerful tool for non-traditional model systems to elucidate
      the molecular basis of complex traits. RESULTS: Here we present a microarray
      constructed with approximately 4500 features, derived from a brain-specific cDNA
      library for the African cichlid fish Astatotilapia burtoni (Perciformes).
      Heterologous hybridization, targeting RNA to an array constructed for a different
      species, is used for eight different fish species. We quantified the concordance
      in gene expression profiles across these species (number of genes and fold
      changes). Although most robust when target RNA is derived from closely related
      species (<10 MA divergence time), our results showed consistent profiles for
      other closely related taxa (approximately 65 MA divergence time) and, to a lesser
      extent, even very distantly related species (>200 MA divergence time).
      CONCLUSION: This strategy overcomes some of the restrictions imposed on model
      systems that are of importance for evolutionary and ecological studies, but for
      which only limited sequence information is available. Our work validates the use
      of expression profiling for functional genomics within a comparative framework
      and provides a foundation for the molecular and cellular analysis of complex
      traits in a wide range of organisms.

PMID- 15238159
TI  - Ordered subset linkage analysis supports a susceptibility locus for age-related
      macular degeneration on chromosome 16p12.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a complex disorder that is
      responsible for the majority of central vision loss in older adults living in
      developed countries. Phenotypic and genetic heterogeneity complicate the analysis
      of genome-wide scans for AMD susceptibility loci. The ordered subset analysis
      (OSA) method is an approach for reducing heterogeneity, increasing statistical
      power for detecting linkage, and helping to define the most informative data set
      for follow-up analysis. OSA assesses the linkage evidence in subsets of
      potentially more homogeneous families by rank-ordering family-specific lod scores
      with respect to trait-associated covariates or phenotypic features. Here, we
      present results of incorporating five continuous covariates into our genome-wide
      linkage analysis of 389 microsatellite markers in 62 multiplex families: Body
      mass index (BMI), systolic (SBP) and diastolic (DBP) blood pressure, intraocular
      pressure (IOP), and pack-years of cigarette smoking. Chromosome-wide significance
      of increases in nonparametric multipoint lod scores in covariate-defined subsets
      relative to the overall sample was assessed by permutation. RESULTS: Using a
      correction for testing multiple covariates, statistically significant lod score
      increases were observed for two chromosomal regions: 14q13 with a lod score of
      3.2 in 28 families with average IOP </= 15.5 (p = 0.002), and 6q14 with a lod
      score of 1.6 in eight families with average BMI >/= 30.1 (p = 0.0004). On
      chromosome 16p12, nominally significant lod score increases (p </= 0.05), up to a
      lod score of 2.9 in 32 families, were observed with several covariate orderings.
      While less significant, this was the only region where linkage evidence was
      associated with multiple clinically meaningful covariates and the only nominally
      significant finding when analysis was restricted to advanced forms of AMD.
      Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were
      primarily affected with neovascular AMD. For all three regions, linkage signals
      at or very near the peak marker have previously been reported. CONCLUSION: Our
      results suggest that a susceptibility gene on chromosome 16p12 may predispose to
      AMD, particularly to the neovascular form, and that further research into the
      previously suggested association of neovascular AMD and systemic hypertension is
      warranted.

PMID- 15238160
TI  - Duplicated genes evolve slower than singletons despite the initial rate increase.
AB  - BACKGROUND: Gene duplication is an important mechanism that can lead to the
      emergence of new functions during evolution. The impact of duplication on the
      mode of gene evolution has been the subject of several theoretical and empirical
      comparative-genomic studies. It has been shown that, shortly after the
      duplication, genes seem to experience a considerable relaxation of purifying
      selection. RESULTS: Here we demonstrate two opposite effects of gene duplication
      on evolutionary rates. Sequence comparisons between paralogs show that, in accord
      with previous observations, a substantial acceleration in the evolution of
      paralogs occurs after duplication, presumably due to relaxation of purifying
      selection. The effect of gene duplication on evolutionary rate was also assessed
      by sequence comparison between orthologs that have paralogs (duplicates) and
      those that do not (singletons). It is shown that, in eukaryotes, duplicates, on
      average, evolve significantly slower than singletons. Eukaryotic ortholog
      evolutionary rates for duplicates are also negatively correlated with the number
      of paralogs per gene and the strength of selection between paralogs. A tally of
      annotated gene functions shows that duplicates tend to be enriched for proteins
      with known functions, particularly those involved in signaling and related
      cellular processes; by contrast, singletons include an over-abundance of poorly
      characterized proteins. CONCLUSIONS: These results suggest that whether or not a
      gene duplicate is retained by selection depends critically on the pre-existing
      functional utility of the protein encoded by the ancestral singleton. Duplicates
      of genes of a higher biological import, which are subject to strong functional
      constraints on the sequence, are retained relatively more often. Thus, the
      evolutionary trajectory of duplicated genes appears to be determined by two
      opposing trends, namely, the post-duplication rate acceleration and the generally
      slow evolutionary rate owing to the high level of functional constraints.

PMID- 15238162
TI  - A double classification tree search algorithm for index SNP selection.
AB  - BACKGROUND: In population-based studies, it is generally recognized that single
      nucleotide polymorphism (SNP) markers are not independent. Rather, they are
      carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus
      possible to choose a much smaller number of SNPs to use as indices for
      identifying haplotypes or haplotype blocks in genetic association studies. We
      refer to these characteristic SNPs as index SNPs. In order to reduce costs and
      work, a minimum number of index SNPs that can distinguish all SNP and haplotype
      patterns should be chosen. Unfortunately, this is an NP-complete problem,
      requiring brute force algorithms that are not feasible for large data sets.
      RESULTS: We have developed a double classification tree search algorithm to
      generate index SNPs that can distinguish all SNP and haplotype patterns. This
      algorithm runs very rapidly and generates very good, though not necessarily
      minimum, sets of index SNPs, as is to be expected for such NP-complete problems.
      CONCLUSIONS: A new algorithm for index SNP selection has been developed. A
      webserver for index SNP selection is available at http://cognia.cu-genome.org/cgi
      bin/genome/snpIndex.cgi/

PMID- 15238163
TI  - RAG: RNA-As-Graphs web resource.
AB  - BACKGROUND: The proliferation of structural and functional studies of RNA has
      revealed an increasing range of RNA's structural repertoire. Toward the objective
      of systematic cataloguing of RNA's structural repertoire, we have recently
      described the basis of a graphical approach for organizing RNA secondary
      structures, including existing and hypothetical motifs. DESCRIPTION: We now
      present an RNA motif database based on graph theory, termed RAG for RNA-As
      Graphs, to catalogue and rank all theoretically possible, including existing,
      candidate and hypothetical, RNA secondary motifs. The candidate motifs are
      predicted using a clustering algorithm that classifies RNA graphs into RNA-like
      and non-RNA groups. All RNA motifs are filed according to their graph vertex
      number (RNA length) and ranked by topological complexity. CONCLUSIONS: RAG's
      quantitative cataloguing allows facile retrieval of all classes of RNA secondary
      motifs, assists identification of structural and functional properties of user
      supplied RNA sequences, and helps stimulate the search for novel RNAs based on
      predicted candidate motifs.

PMID- 15238161
TI  - Hedgehog can drive terminal differentiation of amniote slow skeletal muscle.
AB  - BACKGROUND: Secreted Hedgehog (Hh) signalling molecules have profound influences
      on many developing and regenerating tissues. Yet in most vertebrate tissues it is
      unclear which Hh-responses are the direct result of Hh action on a particular
      cell type because Hhs frequently elicit secondary signals. In developing skeletal
      muscle, Hhs promote slow myogenesis in zebrafish and are involved in
      specification of medial muscle cells in amniote somites. However, the extent to
      which non-myogenic cells, myoblasts or differentiating myocytes are direct or
      indirect targets of Hh signalling is not known. RESULTS: We show that Sonic
      hedgehog (Shh) can act directly on cultured C2 myoblasts, driving Gli1
      expression, myogenin up-regulation and terminal differentiation, even in the
      presence of growth factors that normally prevent differentiation. Distinct
      myoblasts respond differently to Shh: in some slow myosin expression is
      increased, whereas in others Shh simply enhances terminal differentiation.
      Exposure of chick wing bud cells to Shh in culture increases numbers of both
      muscle and non-muscle cells, yet simultaneously enhances differentiation of
      myoblasts. The small proportion of differentiated muscle cells expressing
      definitive slow myosin can be doubled by Shh. Shh over-expression in chick limb
      bud reduces muscle mass at early developmental stages while inducing ectopic slow
      muscle fibre formation. Abundant later-differentiating fibres, however, do not
      express extra slow myosin. Conversely, Hh loss of function in the limb bud,
      caused by implanting hybridoma cells expressing a functionally blocking anti-Hh
      antibody, reduces early slow muscle formation and differentiation, but does not
      prevent later slow myogenesis. Analysis of Hh knockout mice indicates that Shh
      promotes early somitic slow myogenesis. CONCLUSIONS: Taken together, the data
      show that Hh can have direct pro-differentiative effects on myoblasts and that
      early-developing muscle requires Hh for normal differentiation and slow myosin
      expression. We propose a simple model of how direct and indirect effects of Hh
      regulate early limb myogenesis.

PMID- 15238164
TI  - Pre-exposure chemoprophylaxis for HIV: it is time.
AB  - The HIV-1 plague continues unabatedly across sub-Saharan Africa. In Botswana and
      Swaziland, nearly 40% of the entire adult population is already infected. No
      current program is capable of slowing the advancing tide. An effective vaccine
      and widespread treatment are years, if not, decades away. In this most urgent
      situation, I propose that pre-exposure chemoprophylaxis be studied as a means to
      reduce the spread of HIV-1 among at-risk individuals.

PMID- 15238165
TI  - Assessing the determinants of stillbirths and early neonatal deaths using
      routinely collected data in an inner city area.
AB  - BACKGROUND: Within the UK there is considerable variation in the perinatal
      mortality rate. The objective of this study was to assess the factors associated
      with stillbirths and early neonatal deaths (ENND) and the suitability of the
      available databases in a health authority with one of the highest rates in the
      country. METHODS: Two case-control studies were carried out in three hospital
      trusts in the Lambeth, Southwark and Lewisham Health Authority, London, using
      routinely collected information. In one study, 342 stillbirths and 1,368 controls
      were included, and in the other study, 205 ENND and 820 controls were included.
      In the two studies cases and controls were matched for hospital trust. RESULTS: A
      birthweight below 1.5 kg was found in 54% and 48% of the stillbirths and ENND,
      respectively. More than 50% of the cases, stillbirths and ENND, had a length of
      gestation below 32 weeks. Length of gestation, birthweight, emergency caesarean
      section and age of the mother were associated with stillbirths. Birthweight and
      Apgar score at 1 minute as a categorical variable were associated with ENND.
      There was no direct evidence of an effect of social deprivation on the outcomes
      of interest. CONCLUSION: Birthweight and length of gestation are the most
      influential factors on an unfavourable outcome. Conception at an older age has a
      serious impact on stillbirth rates. In our health authority social disadvantage
      did not have a direct impact on stillbirth and ENND. Maternity information
      systems should collect routine data on fewer variables, but their quality in
      terms of value, standardization and completion rates must improve.

PMID- 15238166
TI  - An approach to classifying human resources constraints to attaining health
      related Millennium Development Goals.
AB  - BACKGROUND: For any wide-ranging effort to scale up health-related priority
      interventions, human resources for health (HRH) are likely to be a key to
      success. This study explores constraints related to human resources in the health
      sector for achieving the Millennium Development Goals (MDGs) in low-income
      countries. METHODS AND FRAMEWORK: The analysis drew on information from a variety
      of publicly-available sources and principally on data presented in published
      papers in peer-reviewed journals. For classifying HRH constraints an analytical
      framework was used that considers constraints at five levels: individual
      characteristics, the health service delivery level, the health sector level,
      training capacities and the sociopolitical and economic context of a country.
      RESULTS AND DISCUSSION: At individual level, the decision to enter, remain and
      serve in the health sector workforce is influenced by a series of social,
      economic, cultural and gender-related determinants. For example, to cover the
      health needs of the poorest it is necessary to employ personnel with specific
      social, ethnic and cultural characteristics. At health-service level, the
      commitment of health staff is determined by a number of organizational and
      management factors. The workplace environment has a great impact not only on
      health worker performance, but also on the comprehensiveness and efficiency of
      health service delivery. At health-sector level, the use of monetary and
      nonmonetary incentives is of crucial importance for having the accurate skill mix
      at the appropriate place. Scaling up of priority interventions is likely to
      require significant investments in initial and continuous training. Given the
      lead time required to produce new health workers, such investments must occur in
      the early phases of scaling up. At the same time coherent national HRH policies
      are required for giving direction on HRH development and linking HRH into health
      sector reform issues, the scaling-up of priority interventions, poverty reduction
      strategies, and training approaches. Multisectoral collaboration and the
      sociopolitical and economic context of a country determine health sector
      workforce development and potential emigration. CONCLUSIONS: Key determinants of
      success for achieving international development goals are closely related to
      human-resource development.

PMID- 15238167
TI  - Emergency surgery for recurrent intraabdominal cancer.
AB  - BACKGROUND: Recurrent abdominal cancer can manifest in many ways but there are
      certain situations that are a great challenge to clinicians. Emergency
      presentation is one such situation. Surgeons are faced with a therapeutic dilemma
      that on the one hand most of these patients have a limited life expectancy, and
      on the other surgical procedures are unavoidable. We reviewed our experience of
      recurrent abdominal cancers presenting with acute abdominal symptoms requiring
      emergency. PATIENTS AND METHODS: Over the last 10 years, 81 patients with
      recurrent abdominal cancer presented with an abdominal emergency. Case records,
      operative notes and histology were reviewed. Frequency distributions were
      prepared for clinical, hematological, biochemical parameters, treatment and
      complications. Surgical analysis was carried out by the Kaplan Meier method and
      groups were compared using a log-rank test. RESULTS: The mean age of the patients
      was 70.1 years with a female to male ratio of 1.25. An overall postoperative
      mortality of 11.1% and morbidity of 27.1% was observed. Postoperative infections
      and respiratory complications were the most common causes of morbidity and
      mortality. Emergency resections carried the same risk of mortality and morbidity
      as the other surgical procedures (p > 0.05). Patients who underwent radical or
      palliative resections had a better survival than patients undergoing other
      procedures (p < 0.05). Preoperative Apache II score was found to be single most
      important predictor of postoperative mortality and morbidity. CONCLUSIONS: We
      conclude that surgical resection offers the best chance for improvement in
      survival after emergency surgery for recurrent abdominal cancer. If resection is
      not feasible, the possibility of creating a bypass or enterostomies should be
      considered to improve the patients' quality of life.

PMID- 15238168
TI  - Malaria Panel Assay versus PCR: detection of naturally infected Anopheles melas
      in a coastal village of Equatorial Guinea.
AB  - BACKGROUND: A study was carried out in a village of the mainland region of
      Equatorial Guinea in order to ascertain a) which members of Anopheles gambiae
      complex could be involved in malaria transmission and b) the rate of infectivity
      for Anopheles melas comparing two different methods, a PCR able to detect
      sporozoite-DNA and an immunochromatographic assay MPR (Malaria Rapid Dipstick
      Panel Assay). METHODS: Mosquitoes were sampled at night by indoor captures in two
      houses of a coastal village in Equatorial Guinea (Ayantang). Collected mosquitoes
      were identified as An. gambiae s.l. These were individually dried into silica
      gel. The head-thorax of the An. gambiae s.l. mosquitoes were analysed by PCR to
      verify that the species was of the gambiae complex. Individual head-thorax and
      pools (5 pools) of homogenized mosquitoes employed in Malaria Rapid Panel assay
      (MRP assay) were lysed and DNA was extracted. PCR was designed from the 753 base
      pair insert of pBRKl-14 and DNA was amplified. The relationship between dipstick
      and PCR to detect Plasmodium falciparum sporozoites was measured in terms of
      sensitivity, specificity and test association (Cohen's kappa value). RESULTS: Two
      hundred and sixty-four An. gambiae s.l. females were studied (214 individually
      and five pools with 10 mosquitoes in each). PCR analysis showed that 207
      mosquitoes were An. melas, 3 An. gambiae s.s. and 4 could not be identified. By
      using PCR as the gold standard method when dipstick assay was compared, matching
      results were obtained for 6 mosquitoes and, in one case MRP was positive while
      PCR was not reactive. MRP assay showed a low sensitivity (3.3%) when compared
      with falciparum-DNA detection (17,7% and 14,3%, series A and B respectively).
      Agreement between the two test formats was low (kappa = 0,224). CONCLUSION: It
      was determined that An. melas is the main anopheline vector involved in malaria
      transmission in Ayantang, a coastal village in mainland Equatorial Guinea. A
      comparison of PCR and Vec-Test Assay, concluded that the PCR method proved to be
      a more sensitive and useful tool than the dipstick assay to determine the
      malarial infection rate in mosquitoes in an area of stable and high malaria
      transmission like Equatorial Guinea.

PMID- 15238169
TI  - An audit tool for assessing the appropriateness of carotid endarterectomy.
AB  - BACKGROUND: To update appropriateness ratings for carotid endarterectomy using
      the best clinical evidence and to develop a tool to audit the procedure's use.
      METHODS: A nine-member expert panel drawn from all the Canadian Specialist
      societies that are involved in the care of patients with carotid artery disease,
      used the RAND Appropriateness Methodology to rate scenarios where carotid
      endarterectomy may be performed. A 9-point rating scale was used that permits the
      categorization of the use of carotid endarterectomy as appropriate, uncertain, or
      inappropriate. A descriptive analysis was undertaken of the final results of the
      panel meeting. A database and code were then developed to rate all carotid
      endarterectomies performed in a Western Canadian Health region from 1997 to 2001.
      RESULTS: All scenarios for severe symptomatic stenosis (70-99%) were determined
      to be appropriate. The ratings for moderate symptomatic stenosis (50-69%) ranged
      from appropriate to inappropriate. It was never considered appropriate to perform
      endarterectomy for mild stenosis (0-49%) or for chronic occlusions.
      Endarterectomy for asymptomatic carotid disease was thought to be of uncertain
      benefit at best. The majority of indications for the combination of
      endarterectomy either prior to, or at time of coronary artery bypass grafting
      were inappropriate. The audit tool classified 98.0% of all cases. CONCLUSIONS:
      These expert panel ratings, based on the best evidence currently available,
      provide a comprehensive and updated guide to appropriate use of carotid
      endarterectomy. The resulting audit tool can be downloaded by readers from the
      Internet and immediately used for hospital audits of carotid endarterectomy
      appropriateness.

PMID- 15238170
TI  - [Strategy of mechanical ventilation in acute respiratory distress syndrome: from
      heterogeneous to homogeneous].

PMID- 15238171
TI  - [Diagnosis and treatment of thoracic hydrops in ICU patients].

PMID- 15238173
TI  - [Role of bcl-2 and bax expression in apoptosis of hypoxic pulmonary artery smooth
      muscle cells of rats induced by Na+/H+ exchanger isoform-1 inhibition in vitro].
AB  - OBJECTIVE: To investigate the role of bcl-2 and bax expression in apoptosis of
      hypoxic pulmonary artery smooth muscle cells (PASMCs) of rats induced by Na+/H+
      exchanger isoform-1 (NHE-1) inhibition in vitro. METHODS: Cultured rat PASMCs
      transfected with NHE-1 ribozyme gene (PRZ cell), cultured rat PASMCs transfected
      only with pLXSN vector (PX cell) and non-transfected rat PASMCs (PA cell) were
      obtained in our previous studies. The cells were cultured under low oxygen
      tension (<1% O2) for 0, 2, 6, 12, 24 and 48 hours respectively. Then cell
      apoptosis was examined with terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling (TUNEL). Intracellular Ca2+([Ca2+]i) of cells was measured
      using fluorescence dye Fura-2/AM. The changes in mRNA expression of bcl-2 and bax
      in cells were assessed by semi quantitative reverse transcription-polymerase
      chain reaction (sqRT-PCR). The expression of Bcl-2 protein and Bax protein of
      cells was detected immunohistochemically. RESULTS: In contrast to normal PASMCs
      and cells transfected with pLXSN, the apoptosis rates in recombinant vectors
      transfected cells increased significantly and continuously. [Ca2+]i values were
      also increased in these cells, but the increase extent was remarkably lower than
      in the normal PASMCs (all P<0.01). The expression of bax mRNA and protein of
      cells transfected with recombinant vectors was increased significantly compared
      with cells of other two groups. Meanwhile, the expression of bcl-2 mRNA and
      protein of these cells were decreased significantly. CONCLUSION: The NHE-1
      specific hammerhead ribozymes induce apoptosis of PASMCs under low oxygen tension
      by inhibiting the increase in intracellular Ca2+ concentration, increasing bax
      expression and decreasing bcl-2 expression.

PMID- 15238174
TI  - [Effects of positive end-expiratory pressure on lung recruited volume and
      oxygenation in patients with acute respiratory distress syndrome].
AB  - OBJECTIVE: To access alveolar recruitment with positive end-expiratory pressure
      (PEEP) and to correlate the recruited volume with arterial oxygenation in acute
      respiratory distress syndrome (ARDS). METHODS: Eleven ventilated patients
      satisfying criteria of ARDS were included in the study group. Recruited volume of
      three different PEEP levels [5 cm H2O, 10 cm H2O, 15 cm H2O (1 cm H2O=0.098 kPa)]
      were measured by pressure-volume curve method. Effects of different PEEP levels
      on lung mechanics and gas exchange were compared. RESULTS: Lung recruited volume
      elevated when PEEP increased from 5 cm H2O to 15 cm H2O[(40.2+/-15.3)ml vs.
      (123.8+/-43.1)ml vs. (178.9+/-43.5)ml, all P<0.05]. Arterial oxygenation index
      increased with PEEP and a positive correlation was found between recruited volume
      and changes in arterial oxygenation index (r=0.483, P<0.01). There was no
      significant difference during the static compliance at different PEEP levels at a
      fixed tidal volume (P>0.05). Recruited volume at PEEP 15 cm H2O in the patient
      group with lower inflection point (LIP) was larger than the group without LIP.
      CONCLUSION: Recruited volume increases with PEEP, and the PEEP-induced increase
      in arterial oxygenation is significantly correlated to recruited volume.

PMID- 15238175
TI  - [Relative functional changes in neutrophils in early period of acute lung injury
      in rabbit].
AB  - OBJECTIVE: To explore the relationship of interleukin-8 (IL-8), adherence
      function of neutrophil (PMN) and acute lung injury (ALI). METHODS: Eighteen male
      New Zealand rabbits were divided into two groups randomly: the control group
      (n=8) and the ALI group (n=10). The model of ALI was replicated by using
      intravenous lipopolysaccharide (LPS) in the rabbits of group ALI. Blood pressure,
      heart rate, blood gas analysis, hemogram, CD11b expression intensity on the
      surface of PMN, concentration of serum IL-8 and malondialdehyde (MDA) were
      measured at each time point. Specimens for pathology were obtained at the end of
      experiment. RESULTS: In group ALI, blood pressure, heart rate and pH declined
      obviously. PMN count was lowered obviously at 3 hours and increased at 6 hours to
      some extent. CD11b expression intensity on the surface of PMN, the concentration
      of serum IL-8 and MDA were increased progressively (all P<0.05). The main changes
      in the microscopic examination were inflammatory granulocyte infiltration,
      disseminated thickening of alveolar septa and focal hemorrhages. There were
      significant correlations between CD11b and IL-8 (r2=0.813, Y=26.729X), and
      between CD11b and the grades of pathological changes at 6 hours after intravenous
      LPS (r2=0.771, Y=0.011 02X+5.292). CONCLUSION: LPS could induce the release of
      large amount of IL-8, and it activates the expression of CD11b on the surface of
      PMN, which shows high degree of correlation with IL-8 and the degree of
      pathological changes in the lung. Therefore, both of them could serve as
      sensitive indexes for the diagnosis of ALI.

PMID- 15238178
TI  - [A comparison study on quantitative methods for the recruited volume in sheep
      with acute respiratory distress syndrome].
AB  - OBJECTIVE: To compare equal pressure method with pressure-volume curve method to
      quantify the recruited volume. METHODS: Acute respiratory distress syndrome sheep
      model was induced by intravenous infusion 3 microg/kg lipopolysaccharide (LPS).
      Recruited volume of three different levels of positive end-expiratory pressure
      (PEEP=5, 10, 15 cm H2O) were measured both by pressure-volume curve method and by
      equal pressure method. RESULTS: The time needed to measure recruited volume by
      pressure-volume curve method was 5-6 minutes, which was longer than that of equal
      pressure method. Recruited volume measured by the two methods increased with
      PEEP. No significant difference was found between the recruited volume measured
      by equal pressure method and by equal pressure method at PEEP of 5 cm H2O, they
      were (25.79+/-20.48) ml vs. (63.26+/-54.57) ml (P>0.05), while recruited volume
      at PEEP of 10 cm H2O and 15 cm H2O measured by equal pressure method were lower
      than those measured by the pressure-volume curve method, they were (48.64+/
      30.51)ml vs. (148.14+/-85.42)ml and (71.50+/-58.09)ml vs. (322.86+/-148.42)ml
      (all P<0.05) respectively. CONCLUSION: Though equal pressure method is simple, it
      could not take the place of pressure-volume curve method to quantify recruited
      volume.

PMID- 15238177
TI  - [Protective effect of specific antibody in serum of convalescent patient with
      SARS].
AB  - OBJECTIVE: To investigate inhibitory effect of serum severe acute respiratory
      syndrome (SARS) -specific antibodies from convalescent patients after half an
      year of onset on SARS-CoV-mediated cytopathic response. METHODS: SARS-CoV
      immunoglobulin G (IgG) antibody was determined by enzyme linked immunoadsorbent
      assay (ELISA). Twelve serum samples from convalescent patients, diluted by 1:8
      with maintenance medium, were mixed with the three dilution supernatants of SARS
      CoV. SARS-CoV were isolated, cultured and identified by the Guangzhou Institute
      of Respiratory Disease, and cultured with Vero E6 cell suspension. The extent of
      cytopathic response was observed. RESULTS: The absorbance (A) value of SARS-CoV
      IgG antibody ranged from 0.81 to 2.06 in patients after half an year of SARS
      onset, and form 0.79 to 2.01 in patients before half an year of SARS onset. The
      extent of cytopathic response was decreased by more than 25% in all 12
      convalescent patients, as compared with control serum. CONCLUSION: The A value of
      SARS-CoV IgG antibody in serum of convalescent patients tended to elevate in half
      an year after SARS onset. SARS-CoV IgG antibody could inhibit SARS-CoV-mediated
      cytopathic response, indicating it might be one of protective antibodies.

PMID- 15238180
TI  - [Influence of salbutamol inhalation during volume target pressure control
      ventilation on ventilation parameters in patients with respiratory failure].
AB  - OBJECTIVE: To compare the effects of volume target pressure control ventilation
      (VTPC) and volume control ventilation (VCV) on respiratory mechanics in patients
      with respiratory failure, and to investigate the effects of ventilated parameters
      after salbutamol inhalation. METHODS: Ten patients with mean age (68+/-5) years
      were intubated and mechanically ventilated for acute respiratory failure of
      diverse causes. After 30 minutes with VCV [tidal volume (VT) 8-10 ml/kg],
      measurements of respiratory mechanics were begun, and then the patients were
      ventilated with VTPC for 30 minutes. VCV and VTPC were repeated after salbutamol
      600 microg inhalation. RESULTS: The static compliance (Cst) was (38.4+/-2.7)
      ml/cm H2O (1 cm H2O=0.098 kPa) and airway resistance (Raw) was (20.1+/-2.0) cm
      H2O x L(-1) x s(-1) in 10 patients. With the same tidal volume, peak inspiratory
      pressure (PIP) and mean inspiratory flow [VT/inflation time (Tinflate)]during
      VTPC were lower, but peak inspiratory flow (PIF) was significantly higher than
      that during VCV (all P<0.05). The same plateau pressure (Pplat) was observed
      during VCV as during VTPC, they were (22.1+/-0.9) cm H2O vs. (23.0+/-1.2) cm H2O.
      After salbutamol inhalation, PIP and Raw were significantly decreased in all
      patients (both P<0.05), but no changes were found in Cst and Pplat. PIF and peak
      expiratory flow (PEF) were increased much more during two modes than before
      inhalation (both P<0.05), but Tinflate was decreased (P<0.05). CONCLUSION: VTPC
      is a new mechanical ventilation mode in which closed-loop control theory is used.
      The airway pressure during VTPC is associated with Cst and not influenced by Raw.

PMID- 15238182
TI  - [Adjustment methods of proportional pressure support on weaning during acute
      aggravation in chronic respiratory failure patients with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To study the effects of two adjustment methods of proportional
      pressure support (PPS) on patients with acute aggravation in chronic respiratory
      failure of chronic obstructive pulmonary disease. METHODS: Seventy-five patients
      were randomized to two groups, 30 in proportional adjustment group and 45 in
      target adjustment group, respectively. Suitable flow assist (FA) and volume
      assist (VA) were adjusted with proportional adjustment and target adjustment
      methods respectively according to the ventilation parameters until the weaning of
      ventilation. RESULTS: There were no significant differences in resistance,
      elastic, FA as well as VA on weaning point, duration of mechanical ventilation,
      and successful weaning rate between the two groups (all P>0.05). CONCLUSION: The
      same aim and successful weaning rate could be gained in the target adjustment
      group compared with the proportional adjustment group. More clinical experience
      and more intensive care would be needed in the target adjustment group.

PMID- 15238185
TI  - [A retrospective study on 87 cases with severe acute respiratory syndrome].

PMID- 15238183
TI  - [Treatment of acute respiratory distress syndrome using pressure and volume
      controlled ventilation with lung protective strategy].
AB  - OBJECTIVE: To investigate the significance and effect of pressure controlled
      ventilation (PCV) as well as volume controlled ventilation (VCV) by lung
      protective strategy on respiratory mechanics, blood gas analysis and hemodynamics
      in patients with acute respiratory distress syndrome (ARDS). METHODS: Fifty
      patients with ARDS were randomly divided into PCV and VCV groups with permissive
      hypercapnia and open lung strategy. Changes in respiratory mechanics, blood gas
      analysis and hemodynamics were compared between two groups. RESULTS: Peak
      inspiration pressure (PIP) in PCV group was significantly lower than that in VCV
      group, while mean pressure of airway (MPaw) was significantly higher than that in
      VCV after 24 hours mechanical ventilation. After 24 hours mechanical ventilation,
      there were higher central venous pressure (CVP) and slower heart rate (HR) in two
      groups, CVP was significantly higher in VCV compared with PCV, and PCV group had
      slower HR than VCV group, the two groups had no differences in mean blood
      pressure (MBP) at various intervals. All patients showed no ventilator-induced
      lung injury. Arterial blood oxygenations were obviously improved in two groups
      after 24 hours mechanical ventilation, PCV group had better partial pressure of
      oxygen in artery (PaO2) than VCV group. CONCLUSION: Both PCV and VCV can improve
      arterial blood oxygenations, prevent ventilator-induced lung injury, and have
      less disturbance in hemodynamic parameters. PCV with lung protective ventilatory
      strategy should be early use for patients with ARDS.

PMID- 15238186
TI  - [Correlations of circulating lipoproteins to cytokines and their effects on
      prognosis in patients with SIRS].

PMID- 15238188
TI  - [Dynamic changes and significance of serum TNF-alpha, IL-8 levels in patients
      with acute respiratory distress syndrome after severe trauma].

PMID- 15238190
TI  - [Antegrade-retrograde-warm cardioplegia of myocardial protection in the serious
      heart valve disease].

PMID- 15238199
TI  - Dysphagia.
AB  - Dysphagia is a common complaint that always warrants investigation. The patient's
      history and preliminary testing can help differentiate between the two types of
      dysphagia: oropharyngeal or esophageal. Specific treatments for either of these
      types of dysphagia depend on the underlying etiology. Oropharyngeal dysphagia is
      often associated with a neuromuscular disorder and is treated with swallowing
      rehabilitation. Esophageal dysphagia is usually due to an anatomic defect or a
      motility disorder. Anatomic defects can often be corrected with endoscopic or
      surgical procedures. Motility disorders often benefit from pharmacologic
      treatment. Achalasia may be corrected with an endoscopic procedure with pneumatic
      dilation or, more recently, with injection of botulinum toxin.

PMID- 15238200
TI  - Delayed Gastric Emptying in Functional Dyspepsia.
AB  - Functional dyspepsia is a complex syndrome with a poorly defined pathophysiology,
      resulting in uncertainties in its therapeutic approach. Abnormalities in
      gastrointestinal motility and sensitivity alone or combined seem to play a role
      in a substantial subgroup of patients. Drugs capable of prokinetic effects, such
      as antidopaminergics (eg, metoclopramide, domperidone, levosulpiride) and
      serotonin 5-HT4 receptor agonists (eg, tegaserod) can be potentially used in the
      treatment of dyspeptic patients. Furthermore, 5-HT4 receptor agonists do not
      appear to increase the gastric fundus tone which may also contribute to improved
      symptoms in subsets of patients. Alosetron, a 5-HT3 receptor antagonist, has been
      investigated mainly in irritable bowel syndrome, and the few studies performed in
      functional dyspepsia have provided conflicting results. Erythromycin and related
      derivatives, the motilides, represent another class of prokinetic compounds able
      to accelerate gastric emptying and potentially indicated in functional dyspepsia.
      The stimulatory effect on fundic tone and the occurrence of tachyphilaxis hamper
      the efficacy of these drugs in the long-term treatment. kappa-opioid receptor
      agonists might be useful for functional digestive syndromes because of their
      antinociceptive effects, but there are few available results and most are
      inconclusive. Results are also needed to prove efficacy of antidepressants
      (tricyclic agents and 5-HT reuptake inhibitors). Future clinical trials should be
      performed so that the formal structure required by good clinical practice can be
      adapted to detect significant effects in subgroups of patients with functional
      dyspepsia. Therapy should be ideally targeted to the different pathophysiologic
      abnormalities of these subgroups. The identification of the mechanisms leading to
      symptom generation should facilitate the development of newer and more effective
      therapeutic strategies in functional dyspepsia.

PMID- 15238201
TI  - Proximal Gastric Dysfunction in Functional Dyspepsia: Management Options.
AB  - Functional dyspepsia is a heterogeneous disorder where distinct
      pathophysiological abnormalities are present in subgroups of patients.
      Accommodation of the proximal stomach to a meal is impaired in up to half of the
      patients with functional dyspepsia. This is associated with symptoms of early
      satiety and weight loss. Drug interventions aimed at restoring impaired
      accommodation are currently being studied.

PMID- 15238202
TI  - Noncardiac Chest Pain.
AB  - Noncardiac chest pain (NCCP) is a common condition with significant morbidity and
      economic implications. Psychological factors, gastroesophageal reflux disease
      (GERD), alteration in pain perception, and esophageal dysmotility play an
      important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI)
      therapy is the most effective medical intervention for the treatment of GERD
      related NCCP, as well as the most cost-effective diagnostic strategy for this
      condition. Pain modulators such as tricyclic antidepressants, trazodone, and
      selective serotonin reuptake inhibitors infer a visceral analgesic effect and
      consequently are the treatment of choice for patients with non-GERD-related NCCP.
      Furthermore, cognitive behavioral therapy has also been shown to be useful in the
      management of subset of patients with non-GERD-related NCCP. Newer therapeutic
      modalities and interventions such as lower esophageal sphincter injection of
      botulinum toxin in NCCP patients with spastic esophageal motility disorders,
      theophylline, and 5-HT4 receptor agonists may supplement or replace current
      treatment for non-GERD-related NCCP. Future compounds may include new visceral
      analgesics or medications that interfere with the development of peripheral or
      central sensitization.

PMID- 15238203
TI  - Management of Functional Abdominal Pain.
AB  - The diagnosis of functional abdominal pain should be made based on the Rome II
      symptom criteria with only limited testing to exclude other disease. During
      physical examination the clinician may look for evidence of pain behavior which
      would be supportive of the diagnosis. Reassurance and proper education regarding
      the clinical entity of functional abdominal pain is critical for successful
      treatment and good patient satisfaction. Education should include validation that
      symptoms are real, and that other individuals experience similar symptoms. No
      further treatment may be required for those with mild symptoms. For patients with
      more severe symptoms, a long-term management plan of either pharmacological or
      psychological treatments is warranted. This will require a commitment by both the
      patient and the physician to engage in a partnership with active involvement and
      responsibility by both individuals. The goal of treatment--to decrease pain and
      increase function over time, not to cure the disorder-- should be explained.
      Strong consideration should be made for the use of an antidepressant to treat
      analgesic effects. Tricyclic antidepressants are the mainstay of therapy for
      functional pain disorders. The analgesic effect is generally quicker in onset and
      occurs at a lower dose than their effect on mood. To maximize patient compliance,
      patients should be told the rationale behind their use, warned of the potential
      side effects, and reassured that many of the side effects will disappear with
      time. Choice of an antidepressant should be based on the presence of concomitant
      symptoms (eg, depression), cost, and physician familiarity with specific agents.
      All patients with functional abdominal pain should be screened for underlying
      psychiatric disturbance as an untreated mood disorder will adversely affect
      response to treatment. If a concurrent mood disorder is found, it should be
      treated by either using a higher dose of the tricyclic antidepressant or by
      adding another antidepressant agent. Psychological interventions such as
      cognitive behavioral therapy may be important as adjuvant therapy or as an
      alternative to treatment with antidepressants for those patients who find
      antidepressants ineffective or are intolerant to them. Narcotics and
      benzodiazepines should not be used to treat chronic abdominal pain due to the
      high risk of physical and psychological dependence.

PMID- 15238204
TI  - Treatment of Severe and Intractable Constipation.
AB  - A careful clinical evaluation, exclusion of secondary causes (eg, colonic
      obstruction, metabolic conditions, and drug-induced constipation), and
      assessments of colonic transit and rectal evacuation are necessary to ascertain
      whether constipation is attributable to normal colonic transit, delayed colonic
      transit (ie, slow-transit constipation), or a rectal evacuation disorder (with or
      without delayed colonic transit). Idiopathic slow-transit constipation is a
      clinical syndrome predominantly affecting women and is characterized by
      intractable constipation and delayed colonic transit. This syndrome is attributed
      to disordered colonic motor function and spans a spectrum of variable severity
      ranging from patients who have relatively mild delays in transit, but are
      otherwise indistinguishable from irritable bowel syndrome, at one extreme to
      patients with colonic inertia or chronic megacolon at the other extreme. Most
      patients are treated with one or more pharmacological agent. A subtotal colectomy
      is effective and occasionally indicated for patients with medically refractory
      severe slow-transit constipation, provided that pelvic floor dysfunction has been
      excluded or treated. Pelvic floor dysfunction can be diagnosed by the clinical
      features and anorectal testing. Most patients with pelvic floor dysfunction will
      respond to pelvic floor retraining by biofeedback therapy.

PMID- 15238205
TI  - Treatment of Excessive Intestinal Gas.
AB  - Symptoms of excessive intestinal gas may be related to eructation, excessive or
      odoriferous gas evacuation, and/or abdominal symptom attributed to gas retention.
      Patients with aerophagia and excessive eructation can be usually retrained to
      control air swallowing, but if present, basal dyspeptic symptoms may remain.
      Patients with excessive or odoriferous gas evacuation may benefit from a low
      flatulogenic diet. In patients with gas retention due to impaired anal
      evacuation, anal incoordination can be resolved by biofeedback treatment, which
      also improves fecal retention, and thereby reduces the time for fermentation.
      Other patients complaining of abdominal symptoms that they attribute to
      intestinal gas, probably have irritable bowel syndrome or functional bloating,
      and their treatment options specifically targeting gas-related symptoms basically
      include prokinetics and spasmolytics. There is no consistent evidence to support
      the use of gas-reducing substances, such as charcoal or simethicone.

PMID- 15238206
TI  - Dietary Treatment of the Irritable Bowel Syndrome.
AB  - Most patients with functional gastrointestinal disorders report that food
      ingestion appears to exacerbate their symptoms and consequently conclude that
      they have some form of gastrointestinal food allergy or intolerance. Dietary
      management of functional gastrointestinal conditions is an attractive therapeutic
      option for the patient and physician alike because it is safe and economical and
      empowers the patient to help themselves. However, in practice, dietary
      manipulation frequently yields rather disappointing results. Exclusion diets can
      be helpful, but are labor intensive and occasionally can be very restrictive.
      Laboratory testing for immunoglobulin E food antibodies usually is not helpful,
      except in a small subgroup of patients with diarrhea, predominant irritable bowel
      syndrome (IBS), and atopy. There is some preliminary evidence to suggest that
      elimination diets based on immunoglobulin G food antibody testing may possibly
      have therapeutic potential in IBS, but this requires confirmation.

PMID- 15238207
TI  - Chronic Intestinal Pseudoobstruction.
AB  - Patients with chronic intestinal pseudoobstruction (CIP) experience a
      constellation of symptoms including abdominal pain, nausea, fullness, and malaise
      which fluctuates in severity and invariably result in a diminished quality of
      life. Though surgical resection or transplantation may be an option for some,
      there currently is no cure for CIP. Thus, management strategies utilize
      pharmacologic, intravenous, endoscopic, and surgical techniques to promote
      transit, minimize painful bloating, reduce complications of stasis, and improve
      quality of life. Prokinetic agents such as erythromycin, metoclopramide,
      cisapride, neostigmine, and tegaserod may be effective for acute exacerbations.
      Octreotide may reduce symptoms of bacterial overgrowth and bloating by
      stimulating migrating motor complexes. Enteral tubes for venting and nutritional
      support may reduce hospitalizations. Total parenteral nutrition (TPN), fraught
      with well-known complications, may be the only tolerated source for nutrients and
      fluid. Advanced disease may magnify nutritional problems, difficulties of long
      term intravenous and intestinal access, and poor symptom control. Because the
      initial process may manifest in other intestinal regions following surgery,
      resection of involved segments should be performed with caution. Small intestinal
      transplantation is a high-risk surgery performed in persons unable to tolerate
      intravenous (IV) nutrition. Optimal management for persons with CIP should not
      only provide nutritional and symptom focused care but should be part of a
      supportive network which links patients to their appropriate healthcare needs.

PMID- 15238209
TI  - Environmental stress inhibits the synthesis de novo of proteins involved in the
      photodamage-repair cycle of Photosystem II in Synechocystis sp. PCC 6803.
AB  - The Photosystem II complex (PSII) is susceptible to inactivation by strong light,
      and the inactivation caused by strong light is referred to as photoinactivation
      or photoinhibition. In photosynthetic organisms, photoinactivated PSII is rapidly
      repaired and the extent of photoinactivation reflects the balance between the
      light-induced damage (photodamage) to PSII and the repair of PSII. In this study,
      we examined these two processes separately and quantitatively under stress
      conditions in the cyanobacterium Synechocystis sp. PCC 6803. The rate of
      photodamage was proportional to light intensity over a range of light intensities
      from 0 to 2000 microE m(-2) s(-1), and this relationship was not affected by
      environmental factors, such as salt stress, oxidative stress due to H2O2, and low
      temperature. The rate of repair also depended on light intensity. It was high
      under weak light and reached a maximum of 0.1 min(-1) at 300 microE m(-2) s(-1).
      By contrast to the rate of photodamage, the rate of repair was significantly
      reduced by the above-mentioned environmental factors. Pulse-labeling experiments
      with radiolabeled methionine revealed that these environmental factors inhibited
      the synthesis de novo of proteins. Such proteins included the D1 protein which
      plays an important role in the photodamage-repair cycle. These observations
      suggest that the repair of PSII under environmental stress might be the critical
      step that determines the outcome of the photodamage-repair cycle.

PMID- 15238211
TI  - Correlation between lifetime heterogeneity and kinetics heterogeneity during
      chlorophyll fluorescence induction in leaves: 2. Multi-frequency phase and
      modulation analysis evidences a loosely connected PSII pigment-protein complex.
AB  - We report the first direct decomposition of the fluorescence lifetime
      heterogeneity during multiphasic fluorescence induction in dark-adapted leaves by
      multi-frequency phase and modulation fluorometry (PMF). A very fast component,
      assigned to photosystem I (PSI), was found to be constant in lifetime and yield,
      whereas the two slow components, which are strongly affected by the closure of
      the reaction centers by light, were assigned to PSII. Based on a modified
      "reversible radical pair" kinetic model with three compartments, we showed that a
      loosely connected pigment complex, which is assumed to be the CP47 complex, plays
      a specific role with respect to the structure and function of the PSII: (i) it
      explains the heterogeneity of PSII fluorescence lifetime as a compartmentation of
      excitation energy in the antenna, (ii) it is the site of a conformational change
      in the first second of illumination, and (iii) it is involved in the mechanisms
      of nonphotochemical quenching (NPQ). On the basis of the multi-frequency PMF
      analysis, we reconciled two apparently antagonistic aspects of chlorophyll a
      fluorescence in vivo: it is heterogeneous with respect to the kinetic structure
      (several lifetime components) and homogeneous with respect to average quantities
      (quasi-linear mean tau-Phi relationship).

PMID- 15238210
TI  - Correlation between lifetime heterogeneity and kinetics heterogeneity during
      chlorophyll fluorescence induction in leaves: 1. Mono-frequency phase and
      modulation analysis reveals a conformational change of a PSII pigment complex
      during the IP thermal phase.
AB  - The relationship between the fluorescence lifetime (tau) and yield (Phi) obtained
      in phase and modulation fluorometry at 54 MHz during the chlorophyll fluorescence
      induction in dark-adapted leaves under low actinic light has been investigated.
      Three typical phases have been identified: (i) linear during the OI photochemical
      rise, (ii) convex curvature during the subsequent IP thermal rise, and (iii)
      linear during the PS slow decay. A similar relationship has been obtained in the
      fluorescence induction for the fluorescence yield measured at 685 nm plotted
      versus the fluorescence yield measured at 735 nm. A spectrally resolved analysis
      shows that the curvature of the tau-Phi relationship is not due to chlorophyll
      fluorescence reabsorption effects. Several other hypotheses are discussed and we
      conclude that the curvature of the tau-Phi relationship is due to a variable and
      transitory nonphotochemical quenching. We tentatively propose that this quenching
      results from a conformational change of a pigment-protein complex of Photosystem
      II core antenna during the IP phase and could explain both spectral and temporal
      transitory changes of the fluorescence. A variable blue shift of the 685 nm peak
      of the fluorescence spectrum during the IP phase has been observed, supporting
      this hypothesis.

PMID- 15238212
TI  - A study of molecular interactions in light-harvesting complexes LHCIIb, CP29,
      CP26 and CP24 by Stark effect spectroscopy.
AB  - Electric field-induced absorption changes (electrochromism or Stark effect) of
      the light-harvesting PSII pigment-protein complexes LHCIIb, CP29, CP26 and CP24
      were investigated. The results indicate the lack of strong intermolecular
      interactions in the chlorophyll a (Chl a) pools of all complexes. Characteristic
      features occur in the electronic spectrum of Chl b, which reflect the increased
      values of dipole moment and polarizability differences between the ground and
      excited states of interacting pigment systems. The strong Stark signal recorded
      for LHCIIb at 650-655 nm is much weaker in CP29, where it is replaced by a unique
      Stark band at 639 nm. Electrochromism of Chl b in CP26 and CP24 is significantly
      weaker but increased electrochromic parameters were also noticed for the Chl b
      transition at 650 nm. The spectra in the blue region are dominated by
      xanthophylls. The differences in Stark spectra of Chl b are linked to differences
      in pigment content and organization in individual complexes and point to the
      possibility of electron exchange interactions between energetically similar and
      closely spaced Chl b molecules.

PMID- 15238213
TI  - Tyrosine nitration of carnitine palmitoyl transferase I during endotoxaemia in
      suckling rats.
AB  - Heart carnitine palmitoyl transferase I (CPTI) is inhibited in vivo during
      endotoxaemia and in vitro by peroxynitrite but the biochemical basis of this
      inhibition is not known. The aim of this study was to determine which isoform of
      CPT I is inhibited during endotoxaemia and whether the inhibition is due to
      increased tyrosine nitration. Cardiac mitochondria were isolated from
      endotoxaemic suckling rats. To determine whether M- or L-CPTI was inhibited, we
      carried out titrations with DNP-etomoxir-CoA. Slopes of the titration curves with
      DNP-etomoxir-CoA were no different between control and endotoxaemia, suggesting
      that M-CPTI was specifically inhibited. Immunoprecipitation was carried out using
      an anti-nitrotyrosine antibody. Immunoprecipitated proteins were identified by
      Western blotting with L- and M-CPTI specific antibodies. L-CPTI was nitrated both
      in control and in 2- and 6-h endotoxaemia mitochondria but there was no
      significant difference in the level of nitration. M-CPTI was also nitrated in
      control mitochondria but nitration was significantly increased at both 2- and 6-h
      endotoxaemia. Either 10 mM 3-nitrotyrosine plus 40 microg nitrated-albumin or 0.5
      M dithionite, during immunoprecipitation, greatly decreased immunopositivity for
      M- and L-CPTI on WB. M-CPTI appears to be a novel target for peroxynitrite during
      endotoxaemia, which would alter myocardial substrate selection.

PMID- 15238214
TI  - Expression and induction of CYP4F subfamily in human leukocytes and HL60 cells.
AB  - We investigated the expression of the CYP4F subfamily in human leukocytes and
      HL60 cells. Enzymatic activity assay, immunocytochemical staining, and reverse
      transcription-polymerase chain reaction (RT-PCR) analysis of human leukocytes
      showed that polymorphonuclear leukocytes (PMNs) expressed CYP4F3B and CYP4F12 in
      addition to CYP4F3. Transcription start site of CYP4F3B mRNA in the leukocytes
      was identical to that of CYP4F3 mRNA. The HL60 cells, which were differentiated
      into PMN-like shapes by treatment with all-trans-retinoic acid (RA), also
      expressed CYP4F3, CYP4F3B and CYP4F12. CYP4F3 was expressed in one third of the
      peripheral monocytes, which omega-hydroxylated leukotriene B(4) (LTB(4)) at a
      rate 11 times lower than that of PMN. The cells that were differentiated into a
      form similar to monocytes/macrophages in shape by treatment with 12-myristate 13
      acetate expressed mRNA for CYP4F3 and CYP4F3B. Promoter analysis of the CYP4F3
      gene demonstrated that a region (-174/-90) of this gene was important for its
      promoter activity in the HL60 cells. This is the first report on the distribution
      of different CYP4F isoforms in leukocytes and their induction in HL60 cells.

PMID- 15238208
TI  - The NADPH oxidase of professional phagocytes--prototype of the NOX electron
      transport chain systems.
AB  - The NADPH oxidase is an electron transport chain in "professional" phagocytic
      cells that transfers electrons from NADPH in the cytoplasm, across the wall of
      the phagocytic vacuole, to form superoxide. The electron transporting
      flavocytochrome b is activated by the integrated function of four cytoplasmic
      proteins. The antimicrobial function of this system involves pumping K+ into the
      vacuole through BKCa channels, the effect of which is to elevate the vacuolar pH
      and activate neutral proteases. A number of homologous systems have been
      discovered in plants and lower animals as well as in man. Their function remains
      to be established.

PMID- 15238215
TI  - The extraordinary antioxidant activity of vitamin E phosphate.
AB  - The antioxidant activities of RRR-vitamin E (VE), all-rac-vitamin E (all-rac-VE),
      trolox, RRR-vitamin E acetate (VEA), all-rac-vitamin E phosphate (VEP) and RRR
      vitamin E succinate (VES) were compared. In this study, the rank order in the
      inhibition of lipid peroxidation (LPO) of VE and its derivatives was trolox>VE
      approximately all-rac-VE>VEA>VES. VE and trolox inhibited LPO in non-heated and
      heated rat liver microsomes. It has generally been accepted that this is due to
      scavenging of free radicals by these antioxidants, and during this protection the
      antioxidants are oxidized. VEA and VES have to be converted into VE by esterases
      to obtain antioxidant activity against LPO. VEP, however, had a potent
      antioxidant effect of its own without conversion to VE. In contrast to VE, VEP is
      not consumed during this protection. Of the compounds tested, VEP is the most
      potent in induction of hemolysis of erythrocytes. EPR experiments using the spin
      label 16-doxylstearic acid showed that VEP reduces membrane fluidity, in contrast
      to VE. This indicates that VEP acts as a detergent and forms a barrier that might
      inhibit the transfer of radicals from one polyunsaturated fatty acid to another.
      This new mechanism may form the basis for a new class of antioxidants.

PMID- 15238216
TI  - Induction of antioxidant enzymes by FAK in a human leukemic cell line, HL-60.
AB  - We have established several focal adhesion kinase (FAK) cDNA-transfected HL-60
      (HL-60/FAK) cells which were highly resistant to oxidative stress-induced
      apoptosis. To identify target genes that are involved in HL-60/FAK cells, we
      performed cDNA microarray screening using apoptosis-chip. There, we identified
      the decrease of glutathione peroxidase (GPx). This result prompted us to
      investigate the changes of antioxidant enzymes. Here, we demonstrate that lipid
      peroxidation was suppressed after treatment with hydrogen peroxide in HL-60/FAK
      cells but not vector-transfected HL-60 (HL-60/Vect) cells. Furthermore, we
      demonstrate that HL-60/FAK cells have higher basal reactive oxygen species (ROS)
      levels than the parental HL-60 or HL-60/Vect cells, while ROS accumulation by
      hydrogen peroxide treatment was almost the same in these cells. Basal activity
      and mRNA expression of antioxidant enzymes, particularly of GSH reductase (GRe),
      phospholipid hydroperoxide glutathione peroxidase (PHGPx) were markedly elevated
      in HL-60/FAK cells. In contrast, GPx and catalase levels were decreased in HL
      60/FAK cells. Further, a Src family kinases inhibitor, PP2, suppressed GRe and
      PHGPx mRNA by inactivation of FAK and c-Src in HL-60/FAK cells. These results
      suggest that FAK upregulates antioxidant enzymes and suppresses lipid
      peroxidation, resulting in the anti-apoptotic state for oxidative stress.

PMID- 15238217
TI  - Transforming growth factor-beta down-regulates apolipoprotein M in HepG2 cells.
AB  - Apolipoprotein M (apoM) is a novel apolipoprotein presented mostly in high
      density lipoprotein (HDL) in human plasma, and is exclusively expressed in liver
      and in kidney. The pathophysiological function of apoM has not yet been
      elucidated. Apolipoprotein B (apoB), the characteristic apolipoprotein of low
      density lipoprotein (LDL), is like apoM, a very hydrophobic protein, and
      thereafter they both must co-circulate with lipoprotein particles in plasma. The
      cytokine, transforming growth factor-beta (TGF-beta), has been shown to decreased
      apoB secretion in HepG2 cells, and we hypothesized that TGF-beta may have the
      same effects on apoM expression in HepG2 cells. In the present study, we used
      real-time RT-PCR to analyze apoM and apoB mRNA levels during administration of
      TGF-beta, as well as TGF-alpha, epidermal growth factor (EGF) and hepatic growth
      factor (HGF). TGF-beta significantly inhibited both apoM and apoB mRNA expression
      in HepG2 cells. The inhibitory effects of TGF-beta were dose-dependent, i.e. 1
      ng/ml of TGF-beta decreased apoM mRNA levels by 30%, and 10 or 100 ng/ml of TGF
      beta decreased apoM mRNA levels more than 65%. The effect of TGF-beta on apoB
      mRNA expression was slightly weaker than that of apoM, with a maximum effect at
      10 or 100 ng/ml TGF-beta where apoB mRNA levels decreased about 55%. The
      inhibitory effects of TGF-beta on apoM and apoB mRNA levels also increased with
      increasing incubation time, where the maximum effect was obtained at 24 h.
      Moreover TGF-alpha, EGF and HGF all decreased both apoM and apoB mRNA levels, but
      to a less extent than TGF-beta. Further, all four cytokines had more pronounced
      effects on apoM mRNA expression than apoB mRNA expression. The present study
      suggested that apoM, like apoB, may be involved in the hepatic lipoprotein
      assembly in vivo.

PMID- 15238218
TI  - Essential role of c-Jun induction and coactivator p300 in epidermal growth factor
      induced gene expression of cyclooxygenase-2 in human epidermoid carcinoma A431
      cells.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for high-level
      prostaglandin production during inflammation and carcinogenesis. In this study,
      the transcriptional regulation of COX-2 expression induced by epidermal growth
      factor (EGF) in human epidermoid carcinoma A431 cells was studied. EGF treatment
      induced the expression of COX-2 mRNA, protein, promoter and enzyme activity in a
      time-dependent manner. EGF-induced COX-2 promoter activity was inhibited by
      overexpression of the dominant-negative forms of Ras and ERK2. Induction of COX-2
      and c-Jun by EGF was completely suppressed by MEK inhibitor combined with JNK
      inhibitor. Analysis of the COX-2 promoter binding proteins by gel mobility shift
      assay and DNA affinity precipitation assay revealed that c-Jun and p300 binding
      to CRE/E-box site were responsible for the EGF-induced COX-2 gene transcription.
      Overexpression of p300 significantly enhanced COX-2 promoter activity in cells
      overexpressed of c-Jun or treated with EGF. EGF- and c-Jun-induced transcription
      of COX-2 promoter was repressed by cotransfection of E1A in a dose-dependent
      manner. All together, these results indicated that the EGF-induced expression of
      COX-2 in A431 cells was mediated through the Ras-ERK/JNK signaling pathway, and
      subsequent induction of c-Jun following MAPK activation, in cooperation with
      coactivator p300, was required for the EGF response.

PMID- 15238219
TI  - Effects of peroxisome proliferator-activated receptor alpha activation on
      pathways contributing to cholesterol homeostasis in rat hepatocytes.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) activation by
      fibrates controls expression of several genes involved in hepatic cholesterol
      metabolism. Other genes could be indirectly controlled in response to changes in
      cellular cholesterol availability. To further understand how fibrates may affect
      cholesterol synthesis, we investigated in parallel the changes in the metabolic
      pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased
      HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with
      cholesterogenesis from [(14)C] acetate and [(3)H] mevalonate. The up-regulation
      observed in fenofibrate- and WY-14,643-treated mice was abolished in PPARalpha
      null mice, showing an essential role of PPARalpha. Among the three sterol
      regulatory element-binding protein (SREBP) mRNA species, only SREBP-1c level was
      significantly increased. In ciprofibrate-treated hepatocytes, cholesterol efflux
      was decreased, in parallel with cholesteryl ester storage and bile acids
      synthesis. As expected, AOX expression was strongly induced, supporting evidence
      of the peroxisome proliferation. Taken together, these results show that fibrates
      can cause cholesterol depletion in hepatocytes, possibly in part as a consequence
      of an important requirement of cholesterol for peroxisome proliferation, and
      increase cholesterogenesis by a compensatory phenomenon afterwards. Such
      cholesterogenesis regulation could occur in vivo, in species responsive to the
      peroxisome proliferative effect of PPARalpha ligands.

PMID- 15238220
TI  - Lysophosphatidic acid induces exocytic trafficking of Na(+)/H(+) exchanger 3 by
      E3KARP-dependent activation of phospholipase C.
AB  - Lysophosphatidic acid (LPA) stimulates Na(+)/H(+) exchanger 3 (NHE3) activity in
      opossum kidney proximal tubule (OK) cells by increasing the apical membrane
      amount of NHE3. This occurs by stimulation of exocytic trafficking of NHE3 to the
      apical plasma membrane by an E3KARP-dependent mechanism. However, it is still
      unclear how E3KARP leads to the LPA-induced exocytosis of NHE3. In the current
      study, we demonstrate that stable expression of exogenous E3KARP increases LPA
      induced phospholipase C (PLC) activation and subsequent elevation of
      intracellular Ca(2+) in opossum kidney proximal tubule (OK) cells. Pretreatment
      with U73122, a PLC inhibitor, prevented the LPA-induced NHE3 activation and the
      exocytic trafficking of NHE3. To understand how the elevation of intracellular
      Ca(2+) leads to the stimulation of NHE3, we pretreated OK cells with BAPTA-AM, an
      intracellular Ca(2+) chelator. BAPTA-AM completely blocked the LPA-induced
      increase of NHE3 activity and surface NHE3 amount by decreasing the LPA-induced
      exocytic trafficking of NHE3. Pretreatment with GF109203X, a PKC inhibitor, did
      not affect the percent of LPA-induced NHE3 activation and increase of surface
      NHE3 amount. From these results, we suggest that E3KARP plays a necessary role in
      LPA-induced PLC activation, and that PLC-dependent elevation of intracellular
      Ca(2+) but not PKC activation is necessary for the LPA-induced increase of NHE3
      exocytosis.

PMID- 15238222
TI  - Characterization of a lipid activated CTP:phosphocholine cytidylyltransferase
      from Drosophila melanogaster.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) is an enzyme critical for cellular
      phosphatidylcholine (PC) synthesis, converting phosphocholine and cytidine 5'
      triphosphate (CTP) to CDP-choline. We have isolated a cDNA encoding an isoform of
      CCT from Drosophila melanogaster and expressed the recombinant native and 6 x 
      His-tagged forms using a baculovirus expression system in Spodoptera frugiperda
      (Sf9) insect cells. Immunoblot using anti-phospho amino acid antibodies reveals
      the enzyme is phosphorylated on serine and threonine residues, but not tyrosine.
      The purified native enzyme exhibits a V(max) value of 1352+/-159 nmol CDP
      choline/min/mg, a K(m) value of 0.50+/-0.09 mM for phosphocholine, and a K' (Hill
      constant) value of 0.72+/-0.10 mM for CTP. The 6 x -His-tagged enzyme has similar
      properties with a V(max) value of 2254+/-253 nmol CDP-choline/min/mg, a K(m)
      value of 0.63+/-0.13 mM for phosphocholine and a K' for CTP equal to 0.81+/-0.20
      mM. Each form of the enzyme was activated to a similar extent by synthetic PC
      vesicles containing 50 mol% oleate. The efficiency of lipid activation was
      greatest using PC vesicles containing diphosphatidylglycerol (DPG), significantly
      less efficient activation was seen when phosphatidylserine (PS) and
      phosphatidylinositol (PI) were incorporated into vesicles, and PC alone or PC
      vesicles containing phosphatidylethanolamine were the least efficient enzyme
      activators.

PMID- 15238221
TI  - Human free apolipoprotein A-I and artificial pre-beta-high-density lipoprotein
      inhibit eNOS activity and NO release.
AB  - Little is known about the effects of human free apolipoprotein A-I (Free-Apo A-I)
      and pre-beta-high density lipoprotein (pre-beta-HDL) on the endothelium function.
      In this study, we have investigated the effects of Free-Apo A-I and artificial
      pre-beta-HDL on endothelial NO synthase (eNOS) activity and on NO production by
      endothelial cells. Free-Apo A-I drastically inhibited NO production in human
      umbilical cord vein endothelial cells (HUVECs) and eNOS activity in bovine aortic
      endothelial cells (BAECs). Pre-beta-HDL and serum from human apolipoprotein A-I
      transgenic rabbits inhibited eNOS activity in BAECs but HDL3 did not. Free-Apo A
      I displaced eNOS from BAEC plasma membrane towards intracellular pools without
      affecting eNOS activity and eNOS mass in BAEC crude homogenates. Free-Apo A-I and
      HDL3 did not decrease either caveolin bound to BAEC plasma membrane or caveola
      cholesterol content. As previously described, we showed that HDL3 directly
      induced endothelium-dependent relaxation of rings from rat aorta. We observed
      that pre-beta-HDL significantly decreased endothelium-dependent relaxation of rat
      aortic rings ex vivo.

PMID- 15238223
TI  - Human ATP-binding cassette transporter-2 (ABCA2) positively regulates low-density
      lipoprotein receptor expression and negatively regulates cholesterol
      esterification in Chinese hamster ovary cells.
AB  - We present evidence that the ATP binding-cassette transporter-2 (ABCA2) is a
      sterol-responsive gene that has a role in the trafficking of low-density
      lipoprotein-derived free cholesterol (LDL-FC). In HepG2 cells ABCA2 was
      coordinately expressed with other sterol-responsive genes. Stable constitutive
      expression of ABCA2 in Chinese hamster ovary cells (CHOA2) was accompanied by an
      increase the expression of the low-density lipoprotein receptor (LDLR) and other
      genes involved in the regulation of cholesterol homeostasis. LDLR mRNA was
      elevated greater than ninefold and 3-hydroxy-3-methylglutaryl CoA synthase
      (HMGCoA S) expression was elevated sevenfold in CHOA2 cells. The increase in LDLR
      expression was regulated at the level of transcription; however, culture of CHO
      and CHOA2 cells in medium containing lipoprotein-deficient serum (LPDS) results
      in similar levels of LDLR promoter expression. No differences were measured in
      the dose-dependent uptake of fluorescently labeled 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchorate-LDL (DiI-LDL) between CHO and CHOA2 cells
      cultured in medium containing LPDS. Ultraviolet microscopy revealed a similar
      distribution of the DiI-LDL label in cytoplasmic vesicles. We measured an LDL
      dose-dependent reduction in esterification of LDL-FC in intact CHOA2 cells
      cultured in medium containing LPDS, however, no significant difference was
      measured in acylcoenzyme A:cholesterol acyltransferase (ACAT) activity in cell
      free extracts of CHO and CHOA2 cells. CHO cells or CHOA2 cells treated with the
      hydrophobic amine, U18666A, showed similar filipin staining of unesterified
      cholesterol in cytoplasmic vesicles. Addition of progesterone or U18666A to CHO
      cells elevated ABCA2 expression. Finally, we found that ABCA2 expression was
      elevated in Niemann-Pick type C1 (NPC1) fibroblasts and in Familial
      Hypercholesterolemia (FHC) fibroblasts.

PMID- 15238224
TI  - Differences in mRNA expression of adipocyte-derived factors in response to
      fasting, refeeding and leptin.
AB  - The present study examines whether and to what extent the profiles of adipose
      derived factors are altered in epididymal and subcutaneous adipose tissues of
      long-term fasted/refed and of fasted rats treated by recombinant leptin. Fasting
      was characterized by three successive metabolic phases. Minor differences in the
      time-course and magnitude of response were detected between the two adipose
      sites. Leptin, adiponectin, resistin, adiponutrin, and insulin-like growth factor
      1 (IGF-1) gene expressions differentially decreased according to the fasting
      duration. mRNA levels reached a minimum in late fasting for these secreted
      factors, being decreased by 60-90% for adiponectin, resistin, and IGF-1, 95-98%
      for leptin and by 100% for adiponutrin. Refeeding partially or totally restored
      their mRNA expression in epididymal adipose. Expression levels of apolipoprotein
      E (ApoE), angiotensinogen (AGT), adipsin and macrophage migration inhibitory
      factor (MIF) were either unchanged or slightly affected. In leptin-treated rats,
      leptin mRNA concentrations were significantly decreased in phase 2 of fasting (by
      85%) from levels in control phosphate-buffered saline (PBS)-treated rats in both
      tissues. Leptin treatment also decreased resistin mRNA levels (by 78% in P2L and
      63% in P3L relative to control groups) in subcutaneous adipose. These data
      suggest that adiponectin, resistin, adiponutrin, and IGF-1 could be involved in
      overall energy homeostasis during prolonged fasting, as leptin is. The mechanisms
      that underlie the expressions of these adipose-secreted factors remain to be
      determined.

PMID- 15238225
TI  - Differential basal expression of genes associated with stress response, damage
      control, and DNA repair among mouse tissues.
AB  - Efficient recognition and repair of DNA damage is essential for maintaining
      genomic integrity. Tissues and cell types within tissues appear to vary in both
      DNA damage susceptibilities and cancer incidences, yet the molecular mechanisms
      underlying these differences are not well understood. The purpose of this study
      was to characterize the baseline transcription profiles of selected genes
      involved in DNA damage recognition and repair processes among several tissues of
      healthy adult B6C3F1 mice (testis, brain, liver, spleen and heart), which are
      routinely used by the National Toxicology Program (NTP) to conduct long-term
      chemical carcinogenicity studies. Stress response, damage control and DNA repair
      associated genes were differentially expressed among the tissues examined.
      Overall, stress response genes exhibited the greatest variation among tissues
      with the highest expression in liver and heart while DNA repair genes exhibited
      the least variation. Damage control genes associated with cell cycle regulation
      and DNA repair genes generally had the highest expression in testis. The
      expression levels of several genes were rank correlated with the spontaneous
      cancer incidences among these tissues. Variations in basal expression of DNA
      damage recognition and repair-associated genes among healthy tissues may
      contribute to their differential response to genotoxic agents and susceptibility
      to genetic disease.

PMID- 15238226
TI  - Application of the micronucleus test to exfoliated epithelial cells from the oral
      cavity of beedi smokers, a high-risk group for oral cancer.
AB  - The primary sites for occurrence of oral cancer include the buccal mucosa,
      tongue, alveolus, palate, lip and the floor of the mouth. In this study, an
      attempt was made to estimate the cytogenetic damage in different regions of the
      oral mucosa in people habituated to smoking beedi,which is one of the major forms
      of tobacco consumption in India and believed to be a major risk factor for oral
      cancer. By using the micronucleus assay on exfoliated cells from the buccal
      mucosa, palate and tongue of beedi smokers, we examined an early cellular
      response to the effect of beedi smoking. A total number of 50 randomly selected
      male subjects were included in the study. Case and control groups (smokers and
      non-smokers, respectively) comprised 25 subjects each. The difference in mean
      micronucleated cell count between cases and controls was significant (P <0.01)
      for buccal mucosa and palate, but not for tongue. The correlation between age and
      micronucleus cell count was weak for both cases (r=0.27) and controls (r=0.36).

PMID- 15238228
TI  - Mutagenicity of different textile dye products in Salmonella typhimurium and
      mouse lymphoma cells.
AB  - Textile dyes used within the European Union (EU) were examined for available
      published and unpublished mutagenicity data. Fifty-three dye products that had so
      far not been investigated for mutagenicity were tested in the bacterial reverse
      mutation assay with Salmonella typhimurium (Ames test) according to a
      modification of the OECD 471 guidelines (instead of five strains, only TA98
      and/or TA100 were used with and without metabolic activation (S9-mix)). About 28%
      (15 out of 53) of the dye samples were positive in the Ames test. Fifteen samples
      showed positive results with TA98, two were positive in TA100. The mutagenicity
      of nine Ames-positive textile dye products was further investigated in the mouse
      lymphoma assay (MLA) (OECD 476). Sixty-seven percent (6 out of 9) induced
      genotoxic effects in the MLA. The induction rates (IR) were between 2.1 and 132
      in the bacterial reverse mutation assay and between 2.1 and 15.2 in the MLA. The
      results confirm previous findings that dye products are marketed that are not
      sufficiently tested and that show mutagenic effects in in vitro tests.

PMID- 15238227
TI  - Anti-genotoxicity of coffee against N-methyl-N-nitro-N-nitrosoguanidine in mouse
      lymphoma cells.
AB  - The main aim of this work was to test the hypothesis that instant coffee, a
      commonly consumed polyphenolic beverage with antioxidant activity, can protect
      mammalian cells against genotoxic effects in vitro. For this purpose, the L5178Y
      mouse lymphoma cell line was selected to assess modulatory effects of coffee on
      the genotoxicity of N-methyl-N-nitro-N-nitrosoguanidine (MNNG). We initiated the
      work with a set of preliminary experiments in which the cytokinesis-block
      micronucleus test was performed. Results obtained from these experiments
      demonstrated a dose-related decrease in genotoxicity following co-treatment of
      mouse lymphoma cells with three doses of caffeinated instant coffee. Both pre
      treatment and co-treatment showed significant antigenotoxic effects against MNNG.
      Caffeinated and decaffeinated instant coffee samples inhibited genotoxicity.
      There was no significant change in the antigenotoxic effect of caffeinated
      instant coffee after filtration using a 0.2 microm filter. Similar in vitro
      experiments demonstrated antigenotoxic effects against MNNG when boiled coffee
      was used instead of instant coffee. On the basis of the findings from the above
      preliminary experiments, further work was carried out to evaluate the possible
      protective effects of caffeinated instant coffee against MNNG-induced DNA damage,
      mutation and chromosomal damage. Results from three or five independent
      experiments demonstrated significant protective effects of caffeinated instant
      coffee against MNNG-induced DNA damage in the comet assay, mutation at the Tk
      locus and chromosomal damage in the cytokinesis-block micronucleus test.

PMID- 15238229
TI  - Cytogenetic evaluation of extractable agents from airborne particulate matter
      generated in the city of Catania (Italy).
AB  - In order to document cytogenetic damage associated with air pollution and,
      possibly, with health effects in the city of Catania, Sicily (Italy), we analyzed
      the induction of chromosomal aberrations by extractable agents from airborne
      particulate matter in a Chinese hamster epithelial liver (CHEL) cells. These
      cells retain their metabolic competence to activate different classes of
      promutagens/procarcinogens into biologically active metabolites. Airborne
      particulate matter was obtained from two stationary samplers (stations I and II)
      in two areas endowed by an elevated car transit in the centre of Catania. The
      results obtained clearly indicated that airborne particulate matter from both
      stations I and II proved to be clastogens in CHEL cells but not in Chinese
      hamster ovary (CHO) cells without metabolic activation, indicating that airborne
      particulate mixtures need to be metabolically converted before exerting their
      genotoxic potential. On the basis of these results we can assert that the test
      system employed to identify the cytogenetic potential of airborne particulate
      matter is useful and profitable for environmental control, and helpful to plan
      specific actions aimed at reducing the hazards derived from exposure to polluted
      air.

PMID- 15238230
TI  - Effects of a static magnetic field on cell growth and gene expression in
      Escherichia coli.
AB  - Escherichia coli cultures exposed to a 300mT static magnetic field (SMF) were
      studied in order to analyse possible induced changes in cellular growth and gene
      expression. Biomass was evaluated by visible-light spectrometry and gene
      expression analyses were carried out by use of RNA arbitrarily primed PCR. The
      bacterial strain XL-1Blue, cultivated in traditional and modified Luria-Bertani
      medium, was exposed to SMF generated by permanent neodymium magnetic disks. The
      results show alterations induced by SMF in terms of increased cell proliferation
      and changes in gene expression compared with control groups. Three cDNAs were
      found to be expressed only in the exposed cells, whereas one cDNA was more
      expressed in the controls. One clone, expressed only in the exposed cells,
      corresponds to a putative transposase. This is of particular interest in that it
      suggests that exposure to a magnetic field may stimulate transposition activity.

PMID- 15238231
TI  - The use of mini-organ cultures of human upper aerodigestive tract epithelia in
      ecogenotoxicology.
AB  - The carcinogenic potential of xenobiotics and possible confounders are often
      difficult to differentiate in in vivo studies. In contrast, in vitro studies
      allow investigation of the impact of carcinogens on human target cells under
      standardized conditions. The aim of the present study is to demonstrate whether
      three-dimensional mini organ-cultures (MOCs) of human inferior nasal turbinate
      epithelia may represent a useful model to study genotoxic effects of xenobiotics
      in vitro. Culture of mini organs was performed by cutting 1mm3 pieces from fresh
      specimens of inferior nasal turbinates. After a period of 5-6 days the specimens
      were fully covered with epithelium. On days 7, 9, and 11 of culture, intact MOCs
      from 25 tissue donors were incubated with dimethyl sulfoxide (DMSO) as a negative
      control, or with mono(2-ethylhexyl) phthalate (MEHP), benzo[a]pyrene-7,8-diol
      9,10-epoxide (BPDE), or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). On days 7
      and 11, MOCs were analyzed by the alkaline Comet assay to detect DNA-single
      strand breaks, alkali-labile sites and incomplete excision-repair sites. DNA
      migration after single exposure of non-cultivated fresh specimens was also
      analyzed. In order to detect regimen-specific effects, DNA fragmentation after
      single exposure of intact MOCs was compared with that of cells after separation
      of MOCs on day 7 of culture and consecutive exposure of individual cells.
      Significant DNA migration as a measure of DNA single-strand breaks, alkali-labile
      sites and incomplete excision repair sites, was found after electrophoresis due
      to single and triple exposure of MOCs to MEHP, BPDE and MNNG. Triple exposure of
      MOCs compared to single exposure revealed no difference after exposure to DMSO or
      MEHP, and an increased migration after exposure to BPDE and MNNG. When single
      exposure of isolated cells from fresh specimens was compared with that of intact
      MOCs, DMSO and MNNG had no significantly different effect, whereas exposure to
      MEHP or BPDE caused a reduced migration in cells from MOCs. When exposure of
      isolated cells harvested from MOCs was compared with exposure of intact MOCs,
      MEHP and BPDE caused a significantly lower DNA migration in intact MOCs. MOCs
      provide an in vitro model suitable for the assessment of genotoxic effects of
      environmental pollutants both after single or repetitive exposure. Due to the
      intact structure of the exposed mucosa this model may be a helpful tool in
      mimicking the in vivo situation in ecogenotoxicology studies.

PMID- 15238232
TI  - Anti-clastogenic activity of two structurally related pterocarpans purified from
      Bituminaria bituminosa in cultured human lymphocytes.
AB  - Plant-derived isoflavones are currently receiving much attention because of their
      phyto-estrogenic, antioxidant, anti-mutagenic, and anti-tumor activities. In this
      study we have evaluated the clastogenic and anti-clastogenic activities in human
      lymphocytes of two structurally related pterocarpans, iso-flavonoid derivatives,
      termed erybraedin C and bitucarpin A, recently purified from Bituminaria
      bituminosa and chemically characterized. Mitomycin C (MMC) and the radio-mimetic
      bleomycin (BL) were used as reference clastogens. The end point studied was
      micronucleus formation. The results obtained in this study indicate that
      erybraedin C and bitucarpin A, when assayed alone, do not affect either the
      mitotic index or the cell-proliferation index of human lymphocytes.
      Interestingly, both compounds appear to be non-clastogenic in the range of
      concentrations used. In contrast, both substances seem to affect significantly
      the clastogenic effects induced by BL and MMC. A 1-h pre-exposition of the cell
      culture to erybraedin C was necessary to display its anti-clastogenic potential
      against BL, whereas bitucarpin A was inactive in this respect, with a structure
      activity relationship. In contrast, the clastogenic activity of MMC was
      significantly reduced by both erybraedin C and bitucarpin A, using either a pre
      incubation schedule or simultaneous treatment. These results suggest that the
      protective effects displayed by the two anti-clastogenic compounds against MMC
      could be due to the induction or inhibition of cellular reductive metabolic
      enzymes.

PMID- 15238233
TI  - Randomized controlled trial of dietary intervention: association between level of
      urinary phenolics and anti-mutagenicity.
AB  - We have undertaken a randomized trial to confirm the ability of a class of
      phenolics, flavonoids, to increase urinary anti-mutagenicity in smokers. Ninety
      heavy smokers were recruited and randomly assigned to three groups, who were
      given three different diets. One diet was rich in flavonoids, but not based on
      supplementation ('flavonoid'), one was a normal iso-caloric diet with an adequate
      administration of fruit and vegetables ('normal'), and one was based on
      supplementation of flavonoids in the form of green tea and soy products
      ('supplement'). The urinary anti-mutagenicity-as inhibiting effect of the urinary
      extracts on the mutations induced by MeIQx-was measured in Salmonella typhimurium
      YG1024 in the presence of liver S9 from male Sprague-Dawley rats treated with
      Aroclor 1254. The amount of total phenolics in the urinary extracts was measured
      by use of spectrometric analysis. We found that important dietary modifications
      can be achieved through special recipes and instructions given by a cook during
      an intensive course. The intervention was focused on increasing the flavonoid
      intake, and it was successful in that respect. In fact, differences in flavonoid
      intake were appreciated mainly between the first group (normal diet) and the
      other two (flavonoid-rich and supplemented diet), suggesting that dietary
      modification can be as effective as supplementation. However, both urinary anti
      mutagenicity and the amounts of urinary phenolics did not change as a consequence
      of the trial. These results suggest that only a small fraction of urinary
      phenolics is influenced by dietary changes in the intake of flavonoids, and that
      most urinary anti-mutagens and phenolics are metabolites of dietary flavonoids,
      whose formation is more affected by the activity and diversity of bacterial flora
      in the colon than by the quantity and type of intake. A strong correlation was
      found between urinary phenolics and anti-mutagenicity in all the groups involved
      in the trial. Such correlation was not explained by dietary variables.

PMID- 15238234
TI  - In vitro evaluation of the cytotoxic and mutagenic potential of the 5
      aminolevulinic acid hexylester-mediated photodynamic therapy.
AB  - Photodynamic therapy (PDT) of tumors with 5-aminolevulinic acid hexylester (h
      ALA) causes photo-oxidative reactions in treated tissues. In order to study
      cytotoxic and/or mutagenic effects, cells of the tumor cell line RPMI 2650 as
      well as fibroblasts of the cell line WS 1 were given photodynamic treatment in
      vitro. The cells were photosensitized with a 1mM h-ALA-medium solution for 5h and
      illuminated with different light doses (0.5, 1.0, 1.5 and 2.0 J/cm2) using red
      light (633+/-20 nm). PDT-induced cytotoxic effects were determined by measurement
      of the mitotic index (MI) and the nuclear division index (NDI). Chromosome
      aberrations (CA) and micronuclei (MN) were recorded to study mutagenicity. After
      treatment of the photosensitized RPMI 2650 cells with a light dose of 2.0 J/cm2,
      the MI was significantly decreased to 16.9 per thousand in comparison with that
      of the h-ALA control (33.8 per thousand ). In photosensitized WS 1 cells, light
      doses up to 2.0 J/cm2 showed no significant effect. The NDI of photosensitized
      RPMI 2650 cells was significantly decreased by light doses from 1.0 to 2.0 J/cm2,
      whereas no significant effect was seen in WS 1 cultures. Thus, h-ALA-PDT only
      induced desirable cytotoxic effects in tumor cells, but not in the fibroblasts.
      After application of light doses from 0.5 to 2.0 J/cm2, photosensitized RPMI 2650
      cultures showed CA in 7.0-7.5% of the metaphases, which was not a significant
      increase (h-ALA control: 5.5%). In WS 1 cultures metaphases containing CA varied
      non-significantly from 5.0 to 7.5%. The MN rates were approximately the same in
      illuminated RPMI 2650 cultures and in the corresponding h-ALA control (4.4-4.9
      per thousand ). The MN rates of the illuminated WS 1 cultures also varied non
      significantly from 4.5 to 5.0 per thousand in comparison with the h-ALA control
      (5.5 per thousand ). In the mutagenicity tests the h-ALA-PDT had no significant
      effect, neither on the tumor cells nor on the fibroblasts. In addition to the
      cytogenetic analysis, spectral karyotyping (SKY) was used to characterize the
      cell lines and gain more detailed information on possibly PDT-induced CA. The SKY
      evaluation also showed no significant increase of the CA rate, but confirmed the
      result of the CA test. Thus, within the scope of the experiments performed, a
      mutagenic potential of the h-ALA-PDT can be excluded.

PMID- 15238235
TI  - Mutagenicity of sediment and biomarkers of oxidative stress in fish from aquatic
      environments under the influence of tanneries.
AB  - The mutagenicity of interstitial water and organic extracts from the sediments in
      the Cadeia and Feitoria Rivers, RS, Brazil, were evaluated by Salmonella
      microsuspension bioassay using TA97a, TA98, TA100 and TA102 strains, in the
      absence and presence of S9 mix. At the contaminated site, the mutagenic responses
      for interstitial water, suggested the presence of frameshift and base pair
      substitution mutagens, including oxidative substances. Organic extracts presented
      direct or indicative mutagenesis to the TA97a, TA98 and TA100 strains. In
      general, an exogenous metabolic systems decreased the mutagenicity of the
      samples. High concentrations of total chromium found in the sediment and
      interstitial water as well as total mercury in the sediment of the contaminated
      site, when compared to the control area, may help explain the mutagenic results.
      The livers of Gymnogeophagus gymnogenys collected in this impacted area, compared
      to a non-polluted site, were analyzed for oxidative stress parameters. Compared
      to the controls, there was a significant increase in the activity of superoxide
      dismutase (SOD) at levels of substances reactive to thiobarbituric acid (TBARS),
      and in the chemiluminescence of hepatic cells in fish in the polluted area. The
      concentration of cytochromes P450 and b5 decreased drastically in the fish at the
      polluted site, while the catalase activity did not change. It was possible to
      correlate the biological changes in the fish with the presence of mutagenic
      compounds in sediment and interstitial water in this area.

PMID- 15238236
TI  - DNA single strand breaks in peripheral lymphocytes associated with urinary
      thiodiglycolic acid levels in polyvinyl chloride workers.
AB  - The association between vinyl chloride monomer (VCM) exposure and DNA damage has
      been established. However, the relationship between individual exposure and DNA
      single strand breaks was limited. Since environmental monitoring may not reflect
      the actual exposure, a useful marker of exposure is needed to assess the
      individual exposure. In our previous study, we have found a high correlation
      between air VCM level and urinary thiodiglycolic acid (TdGA) at the commencement
      of the next shift. Here, we further used comet assay to evaluate the relationship
      between urinary TdGA levels and DNA single strand breaks in polyvinyl chloride
      monomer (PVC) workers. Urinary TdGA levels (n=26) at the commencement of the
      following shift were analyzed. Ten of the 26 workers also had personal air
      sampling for air VCM exposure. Questionnaires were administered to obtain
      epidemiological information including detailed history of occupation and
      lifestyles. Workers experiencing air VCM level greater than 5 ppm had higher tail
      moment and tail intensity (%) than those experiencing VCM exposure between 1 and
      5, or <1 ppm, respectively (P < 0.05). The results also revealed that level of
      DNA single strand breaks, including tail moment and tail intensity, were
      increased with urinary TdGA level. The dose-response relationship of urinary TdGA
      level and DNA single strand breaks was particularly significant among the workers
      with 4 mg/g Cr of urinary TdGA level, which is equivalent to 5 ppm air VCM level.
      We concluded that air VCM exposure greater than 5 ppm could induce DNA damage.
      Further sensitive assay should be developed for the diction of DNA damage when
      air VCM exposure below 5 ppm.

PMID- 15238237
TI  - Genotoxicity of malachite green and leucomalachite green in female Big Blue
      B6C3F1 mice.
AB  - Malachite green, a triphenylmethane dye used in aquaculture as an antifungal
      agent, is rapidly reduced in vivo to leucomalachite green. Previous studies in
      which female B6C3F1 mice were fed malachite green produced relatively high levels
      of liver DNA adducts after 28 days, but no significant induction of liver tumors
      was detected in a 2-year feeding study. Comparable experiments conducted with
      leucomalachite green resulted in relatively low levels of liver DNA adducts but a
      dose-responsive induction of liver tumors. In the present study, we fed
      transgenic female Big Blue B6C3F1 mice with 450 ppm malachite green and 204 and
      408 ppm leucomalachite green (the high doses used in the tumor bioassays) and
      evaluated genotoxicity after 4 and 16 weeks of treatment. Neither malachite green
      nor leucomalachite green increased the peripheral blood micronucleus frequency or
      Hprt lymphocyte mutant frequency at either time point; however, the 16-week
      treatment with 408 ppm leucomalachite green did increase the liver cII mutant
      frequency. Similar increases in liver cII mutant frequency were not seen in the
      mice treated for 16 weeks with malachite green or in female Big Blue rats treated
      with a comparable dose of leucomalachite green for 16 weeks in a previous study
      [Mutat. Res. 547 (2004) 5]. These results indicate that leucomalachite green is
      an in vivo mutagen in transgenic female mouse liver and that the mutagenicities
      of malachite green and leucomalachite green correlate with their tumorigenicities
      in mice and rats. The lack of increased micronucleus frequencies and lymphocyte
      Hprt mutants in female mice treated with leucomalachite green suggests that its
      genotoxicity is targeted to the tissue at risk for tumor induction.

PMID- 15238238
TI  - Dominant lethal effect of 60Co gamma radiation in Biomphalaria glabrata (SAY,
      1818).
AB  - The dominant lethal effects of gamma radiation of 60Co in the snail Biomphalaria
      glabrata were studied. Three groups of 13 wild-type snails were irradiated with
      single doses of 2.5; 10 and 20 Gy. Crossings were carried out at intervals of 7,
      17, 23, 30 and 36 days after irradiation. The dominant lethal effect was observed
      only at the first crossing occurring 7 days after irradiation with 2.5 Gy. With
      10 and 20 Gy, the induction of lethal mutations was detected at 7, 17 and 23 days
      after irradiation; a dose-response effect was observed. The effect was stronger 7
      days after irradiation, decreasing in the succeeding crossings up to 30 days.
      Cell-killing effects on germ cells were detected in the crossings at 23 days and
      30 days after irradiation with 20 Gy. After 36 days, frequencies of malformations
      resumed background levels; crossing rates partially recovered. These results show
      that gamma radiation affected all the stages of spermatogenesis. Germ cells at
      later phases were more sensitive to the mutagenic effect of radiation and the
      cell killing effects were observed on the youngest cells. This response was
      similar to the highly homogeneous pattern observed in widely different species
      and allowed us to estimate some parameters of spermatogenesis in B. glabrata.

PMID- 15238239
TI  - The dioxin TCDD protects against aflatoxin-induced mutation in female rats, but
      not in male rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant and a
      potent carcinogen in laboratory rodents. When combined with other environmental
      toxins, it has been shown to increase the (geno)toxicity of some compounds. In
      this study, the effect of TCDD on the mutagenicity of aflatoxin-B1 (AFB1) was
      examined in the rat liver using a lacI transgenic rodent mutation assay. AFB1
      induces GC-->TA transversions. Since TCDD is known to have a differential effect
      in male and female rodents, both sexes were studied. The data showed that a 6
      week pre-exposure to TCDD had no significant effect on the frequency of aflatoxin
      induced mutation in the liver of male rats. However, the TCDD treatment
      completely prevented the aflatoxin-induced transversion mutations in female
      animals.

PMID- 15238240
TI  - Relative cytotoxicity values at the lowest effective concentration for 12
      positive chemicals in the in vitro micronucleus test utilizing Chinese hamster
      ovary cells.

PMID- 15238241
TI  - Gastrins, cholecystokinins and gastrointestinal cancer.
AB  - The gastrointestinal peptide hormones gastrin and cholecystokinin (CCK) are well
      known for their ability to stimulate gastric acid secretion and pancreatic enzyme
      secretion, respectively. The suggestion that gastrin and CCK might also promote
      the development of cancers of the gastrointestinal tract has been controversial,
      but an increasing body of evidence now supports the view that the amidated and
      non-amidated forms of gastrin act as growth factors via different receptors in
      different regions of the gut. For example, animal experiments indicate that
      amidated gastrins are involved in cellular differentiation and repair in the
      gastric mucosa, and synergize with Helicobacter pylori infection in the
      development of gastric carcinoma. In contrast, non-amidated gastrins stimulate
      colonic mucosal growth, accelerate the early steps in colorectal carcinoma
      formation, and are elevated in the tumour and circulation of patients with
      colorectal cancer. Although human pancreatic carcinomas express CCK-1 and CCK-2
      receptors, the role of gastrins and CCK in pancreatic carcinogenesis is yet to be
      established. Further investigation of the possible role of the CCK-2 receptor in
      gastric and pancreatic neoplasia, and of the hypothesis that gastrin precursors
      act as autocrine growth factors in colorectal carcinoma, is warranted. However,
      therapies aimed at the gastrins must be targeted to the relevant gastrin/gastrin
      receptor combination.

PMID- 15238242
TI  - Vaccine and antibody-directed T cell tumour immunotherapy.
AB  - Clearer evidence for immune surveillance in malignancy and the identification of
      many new tumour-associated antigens (TAAs) have driven novel vaccine and antibody
      targeted responses for therapy in cancer. The exploitation of active immunisation
      may be particularly favourable for TAA where tolerance is incomplete but passive
      immunisation may offer an additional strategy where the immune repertoire is
      affected by either tolerance or immune suppression. This review will consider how
      to utilise both active and passive types of therapy delivered by T cells in the
      context of the failure of tumour-specific immunity by presenting cancer patients.
      This article will outline the progress, problems and prospects of several
      different vaccine and antibody-targeted approaches for immunotherapy of cancer
      where proof of principle pre-clinical studies have been or will soon be
      translated into the clinic. Two examples of vaccination-based therapies where
      both T cell- and antibody-mediated anti-tumour responses are likely to be
      relevant and two examples of oncofoetal antigen-specific antibody-directed T cell
      therapies are described in the following sections: (1) therapeutic vaccination
      against human papillomavirus (HPV) antigens in cervical neoplasia; (2) B cell
      lymphoma vaccines including against immunoglobulin idiotype; (3) oncofoetal
      antigens as tumour targets for redirecting T cells with antibody strategies.

PMID- 15238243
TI  - Do human RNA helicases have a role in cancer?
AB  - Human RNA helicases (HRH) represent a large family of enzymes that play important
      roles in RNA processing. The biochemical characteristics and biological functions
      of the majority of HRH are still to be determined. However, there are examples of
      dysregulation of HRH expression in various types of cancer. In addition, some HRH
      have been shown to be involved in the regulation of, or the molecular interaction
      with, molecules implicated in cancer. Other helicases take part in fusion
      transcripts resulting from cancer-associated chromosomal translocation. These
      findings raise the question of whether HRH can contribute to cancer
      development/progression. In this review, I summarize the cancer-related features
      of HRH.

PMID- 15238245
TI  - Intracellular hyaluronan: a new frontier for inflammation?
AB  - A variety of obstacles have hindered the ultrastructural localization of
      hyaluronan (HA). These include a lack of adequate fixation techniques to prevent
      the loss of HA, the lack of highly sensitive and specific probes, and a lack of
      accessibility due to the masking of HA by HA-binding macromolecules such as
      proteoglycans and glycoproteins. Despite these problems, a number of studies,
      both biochemical and histochemical, have been published indicating that HA is not
      restricted to the extracellular milieu, but is also present intracellularly. This
      review focuses on the possible functions of intracellular HA, its potential
      relationships to extracellular HA structures, and implications for inflammatory
      processes.

PMID- 15238246
TI  - O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation
      in modulating cellular function in response to nutrition and stress.
AB  - Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr
      residues by the monosaccharide O-linked beta-N-acetylglucosamine (O-GlcNAc). The
      rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli,
      morphogens, the cell cycle and development suggests a key role for O-GlcNAc in
      signal transduction pathways. Modulation of O-GlcNAc levels has profound effects
      on the functioning of cells, in part mediated through a complex interplay between
      O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc
      modification and phosphorylation are reciprocal. That is, they occur on different
      subsets of the protein population, as the site of attachment occurs on the same
      or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the
      etiology of type II diabetes, the regulation of stress response pathways, and in
      the regulation of the proteasome.

PMID- 15238248
TI  - Glycogenin: the primer for mammalian and yeast glycogen synthesis.
AB  - Glycogen synthesis, whether in mammalian tissue, yeast, or Agrobacterium
      tumefaciens or other bacteria, is initiated by autoglucosylation of a protein.
      Initiation in muscle, by a self-glucosylating protein, glycogenin-1, is the most
      thoroughly studied system, as is described here. These relatively recent findings
      have prompted a rekindling of interest in the intermediates lying between the
      primer and mature mammalian glycogen.

PMID- 15238247
TI  - Cytoplasmic glycosylation of protein-hydroxyproline and its relationship to other
      glycosylation pathways.
AB  - The Skp1 protein, best known as a subunit of E3(SCF)-ubiquitin ligases, is
      subject to complex glycosylation in the cytoplasm of the cellular slime mold
      Dictyostelium. Pro143 of this protein is sequentially modified by a prolyl
      hydroxylase and five soluble glycosyltransferases (GT), to yield the structure
      Galalpha1,Galalpha1,3Fucalpha1,2Galbeta1,3GlcNAcalpha1-HyPro143. These enzymes
      are unusual in that they are expressed in the cytoplasmic compartment of the
      cell, rather than the secretory pathway where complex glycosylation of proteins
      usually occurs. The first enzyme in the pathway appears to be related to the
      soluble animal prolyl 4-hydroxylases (P4H), which modify the transcriptional
      factor subunit HIF-1alpha in the cytoplasm, and more distantly to the P4Hs that
      modify collagen and other proteins in the rER, based on biochemical and
      informatics analyses. The soluble alphaGlcNAc-transferase acting on Skp1 has been
      cloned and is distantly related to the mucin-type polypeptide N-acetyl-alpha
      galactosaminyltransferase in the Golgi of animals. Its characterization has led
      to the discovery of a family of related polypeptide N-acetyl-alpha
      glucosaminyltransferases in the Golgi of selected lower eukaryotes. The Skp1
      GlcNAc is extended by a bifunctional diglycosyltransferase that sequentially and
      apparently processively adds beta1,3Gal and alpha1,2Fuc. Though this structure is
      also formed in the animal secretory pathway, the GTs involved are dissimilar.
      Conceptual translation of available genomes suggests the existence of this kind
      of complex cytoplasmic glycosylation in other eukaryotic microorganisms,
      including diatoms, oomycetes, and possibly Chlamydomonas and Toxoplasma, and an
      evolutionary precursor of this pathway may also occur in prokaryotes.

PMID- 15238249
TI  - CMP-sialic acid synthetase of the nucleus.
AB  - Sialic acids of cell surface glycoconjugates play a pivotal role in the structure
      and function of animal cells and in some bacterial pathogens. The pattern of cell
      surface sialylation is species specific, and, in the animal, highly regulated
      during embryonic development. A prerequisite for the synthesis of sialylated
      glycoconjugates is the availability of the activated sugar-nucleotide cytidine 5'
      monophosphate N-acetylneuraminic acid (CMP-NeuAc), which provides the substrate
      for sialyltransferases. Trials to purify the enzymatic activity responsible for
      the synthesis of CMP-NeuAc from different animal sources demonstrated that the
      major localisation of the enzyme is the cell nucleus. These earlier findings were
      confirmed when the murine CMP-NeuAc synthetase was cloned and the subcellular
      transport of recombinant epitope tagged forms visualised by indirect
      immunofluorescence. Today, the primary sequence elements that direct murine CMP
      NeuAc synthetase into the cell nucleus are known, however, information regarding
      the physiological relevance of the nuclear destination is still not available.
      With this article, we provide a detailed review on earlier and recent findings
      that identified and confirmed the unusual subcellular localisation of the CMP
      NeuAc synthetase. In addition, we take the advantage to discuss most recent
      developments towards understanding structure--function relations of this enzyme.

PMID- 15238250
TI  - Large clostridial cytotoxins: cellular biology of Rho/Ras-glucosylating toxins.
AB  - Mono-O-glycosylation of eukaryotic target proteins is the molecular mechanism of
      bacterial protein toxins of the family of large clostridial cytotoxins. This
      toxin family encompasses several high molecular mass proteins (>250 kDa) of
      various Clostridia species that are implicated in severe human diseases. Toxin A
      and toxin B from Clostridium difficile are the causative agents of
      pseudomembranous colitis and antibiotic-associated diarrhea. Lethal toxin and
      hemorrhagic toxin from Clostridium sordellii as well as alpha-toxin from
      Clostridium novyi are involved in the gas gangrene syndrome. The common mode of
      action of large clostridial cytotoxins is elicited by specific glycosylation of
      small GTP-binding proteins in the cytosol of target cells using activated
      nucleotide sugars as cosubstrates. Specific modification at a single threonine
      residue in the small GTPases renders these important key players of various
      signaling pathways inactive. This minireview intends to give an overview on
      structure-function analysis and mode of action of the large clostridial
      cytotoxins, as well as on the resulting functional consequences of glycosylation
      of target proteins.

PMID- 15238251
TI  - Nucleocytoplasmic lectins.
AB  - This review summarizes studies on lectins that have been documented to be in the
      cytoplasm and nucleus of cells. Of these intracellular lectins, the most
      extensively studied are members of the galectin family. Galectin-1 and galectin-3
      have been identified as pre-mRNA splicing factors in the nucleus, in conjunction
      with their interacting ligand, Gemin4. Galectin-3, -7, and -12 regulate growth,
      cell cycle progression, and apoptosis. Bcl-2 and synexin have been identified as
      interacting ligands of galectin-3, involved in its anti-apoptotic activity in the
      cytoplasm. Although the annexins have been studied mostly as calcium-dependent
      phospholipid-binding proteins mediating membrane-membrane and membrane
      cytoskeleton interactions, annexins A4, A5 and A6 also bind to carbohydrate
      structures. Like the galectins, certain members of the annexin family can be
      found both inside and outside cells. In particular, annexins A1, A2, A4, A5, and
      A11 can be found in the nucleus. This localization is consistent with the
      findings that annexin A1 possesses unwinding and annealing activities of a
      helicase and that annexin A2 is associated with a primer recognition complex that
      enhances the activity of DNA polymerase alpha. Despite these efforts and
      accomplishments, however, there is little evidence or information on an
      endogenous carbohydrate ligand for these lectins that show nuclear and/or
      cytoplasmic localization. Thus, the significance of the carbohydrate-binding
      activity of any particular intracellular lectin remains as a challenge for future
      investigations.

PMID- 15238252
TI  - Glyco-dependent nuclear import of glycoproteins, glycoplexes and glycosylated
      plasmids.
AB  - This short review deals with some properties of nuclear sugar-binding proteins
      also called nuclear lectins, the sugar-dependent nuclear import of
      neoglycoproteins and the attempts of using this pathway to enhance the nuclear
      import of plasmids in order to hopefully increase the expression of transferred
      genes.

PMID- 15238254
TI  - The role of ADP-ribosylation factor and SAR1 in vesicular trafficking in plants.
AB  - Ras-like small GTP binding proteins regulate a wide variety of intracellular
      signalling and vesicular trafficking pathways in eukaryotic cells including plant
      cells. They share a common structure that operates as a molecular switch by
      cycling between active GTP-bound and inactive GDP-bound conformational states.
      The active GTP-bound state is regulated by guanine nucleotide exchange factors
      (GEF), which promote the exchange of GDP for GTP. The inactive GDP-bound state is
      promoted by GTPase-activating proteins (GAPs) which accelerate GTP hydrolysis by
      orders of magnitude. Two types of small GTP-binding proteins, ADP-ribosylation
      factor (Arf) and secretion-associated and Ras-related (Sar), are major regulators
      of vesicle biogenesis in intracellular traffic and are founding members of a
      growing family that also includes Arf-related proteins (Arp) and Arf-like (Arl)
      proteins. The most widely involved small GTPase in vesicular trafficking is
      probably Arf1, which not only controls assembly of COPI- and AP1, AP3, and
      AP4/clathrin-coated vesicles but also recruits other proteins to membranes,
      including some that may be components of further coats. Recent molecular,
      structural and biochemical studies have provided a wealth of detail of the
      interactions between Arf and the proteins that regulate its activity as well as
      providing clues for the types of effector molecules which are controlled by Arf.
      Sar1 functions as a molecular switch to control the assembly of protein coats
      (COPII) that direct vesicle budding from ER. The crystallographic analysis of
      Sar1 reveals a number of structurally unique features that dictate its function
      in COPII vesicle formation. In this review, I will summarize the current
      knowledge of Arf and Sar regulation in vesicular trafficking in mammalian and
      yeast cells and will highlight recent advances in identifying the elements
      involved in vesicle formation in plant cells. Additionally, I will briefly
      discuss the similarities and dissimilarities of vesicle traffic in plant,
      mammalian and yeast cells.

PMID- 15238253
TI  - Applied field nonequilibrium molecular dynamics simulations of ion exit from a
      beta-barrel model of the L-type calcium channel.
AB  - We present results of applied field nonequilibrium molecular dynamics simulations
      (AF NEMD) of a minimal beta-barrel model channel intended to represent an L-type
      calcium channel that suggests a possible relationship between glutamate side
      chain conformational changes and ion flux in calcium channels. The beta-barrel is
      used to provide a scaffolding for glutamate side chains and a confinement for
      electrolyte of dimensions similar to the expected channel structure. It was
      preloaded with ions to explore relative rates of ion exit for different occupancy
      configurations. Our simulations with an asymmetrical flexible selectivity filter
      represented by four glutamate side chains (EEEE), one of which differs in initial
      dihedrals from the other three, indicate a plausible mechanism for the observed
      anomalous mole fraction effect seen in calcium channels. Apparent rates of
      electric field-induced exit from channels preloaded with three Na+ ions are much
      higher than for channels with one Ca2+ followed by two Na+ ions, consistent with
      the common notion that Ca2+ block of Na+ current is due to competition between
      the Ca2+ and Na+ ions for the negatively charged (EEEE) locus. In our model, the
      Ca2+ ion ligates simultaneously to the four negatively charged glutamate side
      chains and sterically blocks the permeation pathway. Ca2+-relief of Ca2+-block is
      suggested by a much higher rate of exit for channels preloaded with three Ca2+
      ions than for channels with two Ca2+ ions.

PMID- 15238255
TI  - Surface behaviour and peptide-lipid interactions of the antibiotic peptides,
      Maculatin and Citropin.
AB  - Surface behaviour of Maculatin 1.1 and Citropin 1.1 antibiotic peptides have been
      studied using the Langmuir monolayer technique in order to understand the peptide
      membrane interaction proposed as critical for cellular lysis. Both peptides have
      a spontaneous adsorption at the air-water interface, reaching surface potentials
      similar to those obtained by direct spreading. Collapse pressures (Pi(c),
      stability to lateral compression), molecular areas at maximal packing and surface
      potentials (DeltaV) obtained from compression isotherms of both pure peptide
      monolayers are characteristic of peptides adopting mainly alpha-helical structure
      at the interface. The stability of Maculatin monolayers depended on the subphase
      and increased when pH was raised. In an alkaline environment, Maculatin exhibits
      a molecular reorganization showing a reproducible discontinuity in the Pi-A
      compression isotherm. Both peptides in lipid films with the zwitterionic
      palmitoyl-oleoyl-phosphatidylcholine (POPC) showed an immiscible behaviour at all
      lipid-peptide proportions studied. By contrast, in films with the anionic
      palmitoyl-oleoyl-phosphatidylglycerol (POPG), the peptides showed miscible
      behaviour when the peptides represented less than 50% of total surface area.
      Additional penetration experiments also demonstrated that both peptides better
      interact with POPG compared with POPC monolayers. This lipid preference is
      discussed as a possible explanation of their antibiotic properties.

PMID- 15238256
TI  - Effect of angiotensin-II on renal Na+/H+ exchanger-NHE3 and NHE2.
AB  - The purpose of the present study was to determine the effect of angiotensin II (A
      II) on membrane expression of Na+/H+ exchange isoforms NHE3 and NHE2 in the rat
      renal cortex. A-II (500 ng/kg per min) was chronically infused into the Sprague
      Dawley rats by miniosmotic pump for 7 days. Arterial pressure and circulating
      plasma A-II level were significantly increased in A-II rats as compared to
      control rats. pH-dependent uptake of 22Na+ study in the presence of 50 microM HOE
      694 revealed that Na+ uptake mediated by NHE3 was increased approximately 88% in
      the brush border membrane from renal cortex of A-II-treated rats. Western
      blotting showed that A-II increased NHE3 immunoreactive protein levels in the
      brush border membrane of the proximal tubules by 31%. Northern blotting revealed
      that A-II increased NHE3 mRNA abundance in the renal cortex by 42%. A-II
      treatment did not alter brush border NHE2 protein abundance in the renal proximal
      tubules. In conclusion, chronic A-II treatment increases NHE3-mediated Na+ uptake
      by stimulating NHE3 mRNA and protein content.

PMID- 15238257
TI  - The stimulation of arginine transport by TNFalpha in human endothelial cells
      depends on NF-kappaB activation.
AB  - In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-alpha
      (TNFalpha) and bacterial lipopolysaccharide (LPS), but neither interferon gamma
      (IFNgamma) nor interleukin 1beta (IL-1beta), stimulate arginine transport. The
      effects of TNFalpha and LPS are due solely to the enhancement of system y+
      activity, whereas system y+L is substantially unaffected. TNFalpha causes an
      increased expression of SLC7A2/CAT-2B gene while SLC7A1/CAT-1 expression is not
      altered by the cytokine. The suppression of PKC-dependent transduction pathways,
      obtained with the inhibitor chelerytrhine, the inhibitor peptide of PKCzeta
      isoform, or chronic exposure to phorbol esters, does not prevent TNFalpha effect
      on arginine transport. Likewise, ERK, JNK, and p38 MAP kinases are not involved
      in the cytokine effect, since arginine transport stimulation is unaffected by
      their specific inhibitors. On the contrary, inhibitors of NF-kappaB pathway
      hinder the increase in CAT2B mRNA and the stimulation of arginine uptake. These
      results indicate that in human endothelial cells the activation of NF-kappaB
      pathway mediates the TNFalpha effects on arginine transport.

PMID- 15238258
TI  - Association of sugar-based carboranes with cationic liposomes: an electron spin
      resonance and light scattering study.
AB  - The possibility of cationic (di-oleoyltrimethylammonium propane, DOTAP)/(L-alpha
      dioleoylphosphatidyl-ethanolamine, DOPE) liposomes to act as carriers of
      boronated compounds such as 1,2-dicarba-closo-dodecaboran(12)-1-ylmethyl](beta-D
      galactopyranosyl)-(1-->4)-beta-D-glucopyranoside and 1,2-di-(beta-D-gluco
      pyranosyl-ox)methyl-1,2-dicarba-closo-dodeca-borane(12) has been investigated by
      Electron Spin Resonance (ESR) of n-doxyl stearic acids (n-DSA) and Quasi-Elastic
      Light Scattering (QELS). Both these carboranes have potential use in Boron
      Neutron Capture Therapy (BNCT), which is a targeted therapy for the treatment of
      radiation resistant tumors. They were shown to give aggregation both in plain
      water and in saline solution. Carborane aggregates were, however, disrupted when
      DOTAP/DOPE liposome solutions were used as dispersing agents. The computer
      analysis of the ESR spectra from carborane-loaded liposomes allowed to establish
      an increase of the order degree in the liposome bilayer with increasing carborane
      concentration, together with a decreased mobility. The same discontinuities of
      both correlation time and order parameter with respect to temperature variations
      were observed in carborane-containing and carborane-free liposomes. This
      suggested that a homogeneous dispersion of nitroxides and carboranes occurred in
      the liposome bilayer. The ESR line shape analysis proved that no dramatic changes
      were induced in the liposome environment by carborane insertion. QELS data showed
      that the overall liposome structure was preserved, with a slight decrease in the
      mean hydrodynamic radius and increase in polydispersity caused by the guest
      molecules.

PMID- 15238259
TI  - Identification of phalloidin uptake systems of rat and human liver.
AB  - To determine whether the liver toxin phalloidin is transported into hepatocytes
      by one of the known bile salt transporters, we expressed the sodium-dependent
      Na+/taurocholate cotransporting polypeptide (Ntcp) and several sodium-independent
      bile salt transporters of the organic anion transporting polypeptide (OATP/SLCO)
      superfamily in Xenopus laevis oocytes and measured uptake of the radiolabeled
      phalloidin derivative [3H]demethylphalloin. We found that rat Oatp1b2 (previously
      called Oatp4 (Slc21a10)) as well as human OATP1B1 (previously called OATP-C
      (SLC21A6)) and OATP1B3 (previously called OATP8 (SLC21A8)) mediate uptake of
      [3H]demethylphalloin when expressed in X. laevis oocytes. Transport of increasing
      [3H]demethylphalloin concentrations was saturable with apparent Km values of 5.7
      microM (Oatp1b2), 17 microM (OATP1B1) and 7.5 microM (OATP1B3). All other tested
      Oatps/OATPs as well as the rat liver Ntcp did not transport [3H]demethylphalloin.
      Therefore, we conclude that rat Oatp1b2 as well as human OATP1B1 and OATP1B3 are
      responsible for phalloidin uptake into rat and human hepatocytes.

PMID- 15238260
TI  - DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery: zeta potential
      measurements and electron spin resonance spectra.
AB  - Non-viral vectors represent an important alternative in gene delivery. Among
      these vectors, cationic liposomes are widely studied, because of their ability to
      form stable complexes with DNA fragments (lipoplexes). In the present work, we
      report on the characterization by electron spin resonance (ESR) spectroscopy and
      zeta potential measurements of cationic liposomes and of their complexes with
      oligonucleotides. Liposomes were made with a zwitterionic lipid, DOPE, and a
      cationic lipid, either DOTAP or DC-Chol. Oligonucleotides were the 20-base single
      strand polyA, the 20-base single strand polyT, and the corresponding double
      strand dsAT. The zeta potential as a function of the oligonucleotide/lipid+ ratio
      gave an S-shaped titration curve. Well-defined surface potential changes took
      place upon charge compensation between the cationic lipid heads and the phosphate
      groups on the oligonucleotides. The inversion point depended on the specific
      system under study. The bilayer properties and the changes that occurred with the
      incorporation of DNA fragments were also monitored by ESR spectroscopy of
      appropriately tailored spin probes. For all the systems investigated, the ESR
      spectra showed that no major alteration took place after lipoplex formation and
      molecular packing remained substantially unchanged. Both zeta potential and ESR
      measurements were in favor of an external mode of packing of the lipoplexes.

PMID- 15238261
TI  - Molecular mapping of the conductance activity linked to tAE1 expressed in Xenopus
      oocyte.
AB  - It was previously shown that expressed in Xenopus oocyte the trout (tAE1) and the
      mouse (mAE1) anion exchangers behave differently: both elicit anion exchange
      activity but only tAE1 induces a transport of organic solutes correlated with an
      anion conductance. In order to identify the structural domains involved in the
      induction of tAE1 channel activity, chimeras have been prepared between mouse and
      trout AE1. As some constructs were not expressed at the plasma membrane, skate
      exchanger (skAE1) was used instead of mouse exchanger to complete the structure
      function analysis. The present paper shows that skAE1, highly similar to mAE1,
      does not induce a chloride conductance when expressed in Xenopus oocyte.
      Construct expression analysis showed that only tAE1 transmembrane domain is
      linked to the anion conductance. More precisely, we identified two regions
      composed of helices 6, 7 and 8 and putative helices 12 and 13 which are required
      for this function.

PMID- 15238262
TI  - Evidence for heterodimers of 2,4,5-trichlorophenol on planar lipid layers. A FTIR
      ATR investigation.
AB  - Trichlorophenols are weak acids of high hydrophobicity and are able to transport
      protons across the mitochondrial membrane. Thus the proton motive force is
      dissipated and the ATP production decreased. In situ Fourier Transform Infrared
      Attenuated Total Reflection (FTIR-ATR) experiments with 2,4,5-trichlorophenol
      (TCP) adsorbed to model membranes resulted in good evidence for the formation of
      the TCP-heterodimer. Two surfaces were examined: a dipalmitoyl phosphatidic acid
      (DPPA) monolayer and a planar DPPA/1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) bilayer. TCP was adsorbed from 1 to 3 mM solutions at pH
      6.0 to the lipid layers leading to surface layers at the water/lipid interface.
      Difference spectra showed an effect on DPPA acyl chains even when it was covered
      with POPC. Time-resolved measurements revealed two distinct adsorption processes,
      which were assigned to TCP and its deprotonated anion (phenoxide), respectively.
      For DPPA/POPC bilayers, the adsorption of TCP was faster than that of its
      phenoxide, whereas adsorption of both species to DPPA monolayers proceeded with
      similar velocity. In both cases, phenoxide formation at the membrane was found to
      be delayed with respect to phenol adsorption. Phenoxide and phenol were retained
      after replacing the TCP solution with buffer. For the retained species, we
      estimated a phenol/phenoxide molar ratio of 1 at pH 6.0 (pKa=6.94 for TCP),
      demonstrating strong evidence for heterodimer formation.

PMID- 15238263
TI  - Subconductance states in OmpF gating.
AB  - Discrepancies were noted in the published conductance of the Escherichia coli
      porin OmpF. Results from various papers are hard to compare because of the use of
      different channel preparations, salt types and concentrations, and
      electrophysiological techniques (black lipid membrane (BLM) vs. patch clamp). To
      reconcile these data, we present a side-by-side comparison of OmpF activity
      studied with the two techniques on the same preparation of pure protein, and in
      the same low salt concentrations (150 mM KCl). The novel aspect of OmpF porin
      behavior revealed by this comparison is the ubiquitous existence of states of
      smaller conductance than the monomeric conductance (subconductance states),
      regardless of the techniques or experimental conditions used, and the drastic
      enhancement of subconductance gating by polyamines. Transitions to subconductance
      states have received little attention in previous publications, in particular
      when BLM electrophysiology was used. Monomeric closures are rare in recordings at
      clamped potentials, at least at voltages lower than approximately 100-120 mV.
      Most closing activity is in the form of subconductance gating, which becomes more
      dominant in the presence of spermine, with a more frequent and prolonged
      occupation of these substates. A discussion of the molecular basis for this
      hallmark behavior of porin is presented.

PMID- 15238264
TI  - Membrane order conservation in raft and non-raft regions of hepatocyte plasma
      membranes from thermally acclimated rainbow trout.
AB  - Homeoviscous adaptation (HVA), the thermal conservation of membrane
      fluidity/order at different body temperatures, has been observed to varying
      degrees in different membranes. However, HVA has not been studied in raft and non
      raft regions of the plasma membrane (PM) separately. Rafts are ordered PM
      microdomains implicated in signal transduction, membrane traffic and cholesterol
      homeostasis. Using infrared spectroscopy, we measured order in raft-enriched PM
      (raft) and raft-depleted PM (RDPM) isolated from hepatocytes of rainbow trout
      (Oncorhynchus mykiss) acclimated to 5 and 20 degrees C. We found approximately
      130% and 90% order compensation in raft and RDPM, respectively, suggesting their
      independent regulation. Raft was more ordered than RDPM in the warm-acclimated
      trout, a difference fully explained by a 58% enrichment of cholesterol, compared
      to RPDM. Unexpectedly, raft and RDPM from cold-acclimated trout did not differ in
      cholesterol content or order. Freezing the membrane samples during preparation
      had no effect on order. Treatment with cyclodextrin depleted cholesterol by 36%,
      56%, and 55%, producing significant decreases in order in raft and RDPM from warm
      acclimated trout and RDPM from cold-acclimated trout, respectively. However, a
      69% depletion of cholesterol from raft from cold-acclimated trout had no
      significant effect on order. This result, and the lack of a difference in order
      between raft and RDPM, suggests that raft and non-raft PM in cold-acclimated
      trout are not spatially segregated by phase separation due to cholesterol.

PMID- 15238265
TI  - Allophycocyanin and energy transfer.
AB  - Allophycocyanin is a biliprotein located in the core of the phycobilisome. The
      biliprotein is isolated and purified as a trimer (alpha3beta3), where a monomer
      is an alphabeta structure. Each alpha and beta subunit has a single noncyclic
      tetrapyrrole chromophore, called phycocyanobilin. The trimer of allophycocyanin
      has an unusual absorption maximum at 650 nm with a shoulder at 620 nm, while the
      monomer has an absorption maximum at 615 nm. Two explanations have been proposed
      for the 650-nm maximum. In one, this maximum is produced by the interaction of a
      particular local protein environment for three of the chromophores, causing them
      to red shift, while the other three chromophores are at a higher energy. Energy
      is transferred from the high- to the low-energy chromophores by Forster resonance
      energy transfer, the donor-acceptor model. In the second proposal, there is
      strong exciton coupling between two chromophores of the trimer that closely
      approach across the monomer-monomer interface. The strong interaction causes
      exciton splitting and a red shift in the absorption. There are three of these
      strongly coupled chromophore pairs, and energy is transferred between the two
      exciton states of a pair by internal conversion. A variety of biophysical methods
      have been used to examine this question. Although evidence supporting both models
      has been produced, sophisticated ultra fast fluorescence results from a plethora
      of approaches now firmly point to the latter strong coupling hypothesis as being
      more likely. Between the different strongly coupled pairs, Forster resonance
      energy transfer should occur. For monomers of allophycocyanin, Forster resonance
      energy transfer occurs between the two chromophores.

PMID- 15238266
TI  - Global and target analysis of time-resolved spectra.
AB  - In biological/bioenergetics research the response of a complex system to an
      externally applied perturbation is often studied. Spectroscopic measurements at
      multiple wavelengths are used to monitor the kinetics. These time-resolved
      spectra are considered as an example of multiway data. In this paper, the
      methodology for global and target analysis of time-resolved spectra is reviewed.
      To fully extract the information from the overwhelming amount of data, a model
      based analysis is mandatory. This analysis is based upon assumptions regarding
      the measurement process and upon a physicochemical model for the complex system.
      This model is composed of building blocks representing scientific knowledge and
      assumptions. Building blocks are the instrument response function (IRF), the
      components of the system connected in a kinetic scheme, and anisotropy properties
      of the components. The combination of a model for the kinetics and for the
      spectra of the components results in a more powerful spectrotemporal model. The
      model parameters, like rate constants and spectra, can be estimated from the
      data, thus providing a concise description of the complex system dynamics. This
      spectrotemporal modeling approach is illustrated with an elaborate case study of
      the ultrafast dynamics of the photoactive yellow protein.

PMID- 15238267
TI  - Subcellular localization of VDAC in mitochondria and ER in the cerebellum.
AB  - The voltage-dependent anion channel (VDAC) provides passage for adenine
      nucleotides, Ca2+ and other metabolites into and from mitochondria. Here, the
      intracellular localization and oligomeric organization of VDAC in brain
      mitochondria and ER are demonstrated. Immunohistochemical staining of VDAC in rat
      cerebellum showed high labeling of the Purkinje neurons. Immunogold labeling and
      EM analysis of the cerebellar molecular layer showed specific VDAC immunostaining
      of the mitochondrial outer membrane, highly enhanced in contact sites between
      mitochondria or between mitochondria and associated ER. Purified ER membranes
      contain VDAC, but not other mitochondrial proteins. Chemical cross-linking of
      isolated mitochondria, ER or purified VDAC demonstrated the existence of VDAC in
      oligomeric form. Based on the enrichment of VDAC in the junctional face of
      closely associated mitochondrial and ER membranes and the existence of VDAC
      oligomers, we propose an involvement of VDAC in specialized intermembrane
      communication between mitochondria or between ER and mitochondria, serving to
      complement the tight structural and functional coupling observed between these
      organelles.

PMID- 15238268
TI  - Redox properties of Arabidopsis cytochrome c6 are independent of the loop
      extension specific to higher plants.
AB  - Cytochrome c6 (cytc6) from Arabidopsis differs from the cyanobacterial and algal
      homologues in several redox properties. It is possible that these differences
      might be due to the presence of a 12 amino acid residue loop extension common to
      higher plant cytc6 proteins. However, homology modelling suggests this is not the
      case. We report experiments to test if differences in biochemical properties
      could be due to this extension. Analysis of mutant forms of Arabidopsis cytc6 in
      which the entire extension was lacking, or a pair of cysteine residues in the
      extension had been exchanged for serine, revealed no significant effect of these
      changes on either the redox potential of the haem group or the reactivity towards
      Photosystem I (PSI). We conclude that the differences in properties are due to
      more subtle unidentified differences in structure, and that the sequence
      extension in the higher plant proteins has a function yet to be identified.

PMID- 15238269
TI  - Changes in polyphasic chlorophyll a fluorescence induction curve upon inhibition
      of donor or acceptor side of photosystem II in isolated thylakoids.
AB  - The action of various inhibitors affecting the donor and acceptor sides of
      photosystem II (PSII) on the polyphasic rise of chlorophyll (Chl) fluorescence
      was studied in thylakoids isolated from pea leaves. Low concentrations of diuron
      and stigmatellin increased the magnitude of J-level of the Chl fluorescence rise.
      These concentrations barely affected electron transfer from PSII to PSI as
      revealed by the unchanged magnitude of the fast component (t(1/2) = 24 ms) of
      P700+ dark reduction. Higher concentrations of diuron and stigmatellin suppressed
      electron transport from PSII to PSI, which corresponded to the loss of thermal
      phase, the Chl fluorescence rise from J-level to the maximal, P-level. The effect
      of various concentrations of carbonylcyanide m-chlorophenylhydrazone (CCCP),
      which abolishes S-state cycle and binds at the plastoquinone site on QB, the
      secondary quinone acceptor PSII, on the Chl fluorescence rise was very similar to
      that of diuron and stigmatellin. Low concentrations of diuron, stigmatellin, or
      CCCP given on the background of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD),
      which is shown to initiate the appearance of a distinct I-peak in the kinetics of
      Chl fluorescence rise measured in isolated thylakoids [BBA 1607 (2003) 91],
      increased J-step yield to I-step level and retarded Chl fluorescence rise from I
      step to P-step. The increased J-step fluorescence rise caused by these three
      types of inhibitors is attributed to the suppression of the non-photochemical
      quenching of Chl fluorescence by [S2+ S3] states of the oxygen-evolving complex
      and oxidized P680, the primary donor of PSII reaction centers. In the contrary,
      the decreased fluorescence yield at P step (J-P, passing through I) is related to
      the persistence of a "plastoquinone"-type quenching owing to the limited
      availability of photochemically generated electron equivalents to reduce PQ pool
      in PSII centers where the S-state cycle of the donor side is modified by the
      inhibitor treatments.

PMID- 15238270
TI  - Nonenzymatic chromophore attachment in biliproteins: conformational control by
      the detergent Triton X-100.
AB  - While chromophore attachment to alpha-subunits of cyanobacterial biliproteins has
      been studied in some detail, little is known about this process in beta-subunits.
      The ones of phycoerythrocyanin and C-phycocyanin each carry two phycocyanobilin
      (PCB) chromophores covalently attached to cysteins beta84 and beta155. The
      differential nonenzymatic reconstitution of PCB to the apoproteins, PecA, PecB,
      CpcA and CpcB, as well as to mutant proteins of the beta-subunits lacking either
      one of the two binding cysteins, was studied using overexpression of the
      respective genes. PCB adds selectively to Cys-84 of CpcA, CpcB, PecA, and PecB,
      but the bound chromophore has a nonnative configuration, and in the case of CpcA,
      is partly oxidized to mesobiliverdin (MBV). The oxidation is independent of
      thiols but can be suppressed by ascorbate. The addition to Cys-beta84 is
      suppressed in the presence of detergents like Triton X-100, in favor of an
      addition to Cys-beta155 yielding the correctly bound chromophore. Triton X-100
      also inhibits oxidation of the chromophore during addition to CpcA. The effect of
      Triton X-100 was studied on the isolated components of the reconstitution system.
      Absorption, fluorescence and circular dichroism spectra indicate a major
      conformational change of the chromophore upon addition of the detergent, which
      probably controls the site selectivity of the addition reaction, and inhibits the
      oxidation of PCB to MBV.

PMID- 15238271
TI  - Abnormal cardiac energetics in patients carrying the A3243G mtDNA mutation
      measured in vivo using phosphorus MR spectroscopy.
AB  - Cardiomyopathy is a frequent cause of morbidity and mortality in patients
      carrying the A3243G transition in the mitochondrial DNA (mtDNA) tRNALeu(UUR)
      gene, the most common heteroplasmic single mtDNA defect. We used phosphorus
      magnetic resonance spectroscopy (31P-MRS) to look for evidence of an in vivo
      bioenergetics defect in patients carrying the A3243G mtDNA mutation with and
      without echocardiographic signs of left ventricle hypertrophy (LVH). Eight
      patients, three with LVH, carrying the A3243G mtDNA mutation and 10 healthy
      subjects underwent one-dimensional chemical shift imaging 31P-MRS. In the
      patients, mean cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP)
      (1.55 +/- 0.58) was significantly reduced compared to the control group (2.34 +/-
      0.14; P < 0.001). Cardiac PCr/ATP was within the normal range only in one case
      that showed normal echocardiography. Our results point to a central role of
      bioenergetics deficit in the development of cardiac hypertrophy in patients with
      the A3243G mtDNA mutation. Impaired cardiac energy metabolism in patients with
      normal echocardiography suggests that the enhancement of mitochondrial function
      may be beneficial not only to patients with cardiac hypertrophy but also to those
      patients carrying the mutation in the absence of signs of cardiac hypertrophy
      and/or dysfunction but with cardiac bioenergetics deficit.

PMID- 15238272
TI  - Effects of N-acylethanolamines on mitochondrial energetics and permeability
      transition.
AB  - Effects of N-acylethanolamines (NAEs): N-arachidonoylethanolamine (anandamide), N
      oleoylethanolamine and N-palmitoylethanolamine, on energy coupling and
      permeability of rat heart mitochondria were investigated. In nominally Ca2+-free
      media, these compounds exerted a weak protonophoric effect manifested by
      dissipation of the transmembrane potential and stimulation of resting state
      respiration. The strongest action was exhibited by N-arachidonoylethanolamine,
      followed by N-oleoylethanolamine, whereas N-palmitoylethanolamine was almost
      inactive. These protonophoric effects were resistant to cyclosporin A (CsA) and
      were much weaker than those of corresponding nonesterified fatty acids. In
      uncoupled mitochondria N-arachidonoylethanolamine and N-oleoylethanolamine partly
      inhibited mitochondrial respiration with glutamate and succinate but not with
      tetramethyl-p-phenylenediamine (TMPD) plus ascorbate as respiratory substrates.
      In mitochondria preloaded with small amounts of Ca2+, NAEs produced a much
      stronger dissipation of the membrane potential and a release of accumulated
      calcium, both effects being inhibited by CsA, indicative for opening of the
      mitochondrial permeability transition pore (PTP). Again, the potency of this
      action was N-arachidonoylethanolamine>N-oleoylethanolamine>N
      palmitoylethanolamine. However, in spite of making the matrix space accessible to
      external [14C]sucrose, N-arachidonoylethanolamine and N-oleoylethanolamine
      resulted in only a limited swelling of mitochondria and diminished the rate of
      swelling produced by high Ca2+ load.

PMID- 15238273
TI  - Photosystem I is not solely responsible for oxygen reduction in isolated
      thylakoids.
AB  - It was found that the contribution of segments of photosynthetic electron
      transport chain (PETC) besides Photosystem I (PSI) to oxygen reduction increased
      with increase in light intensity, and at high intensities achieved 50% at pH 5.0,
      and was higher than 60% at pH 6.5 and pH 7.8. The data are explained as the
      result of O2 reduction in plastoquinone (PQ) pool as well as in PSI followed by
      reduction of superoxide radicals generated in both processes by
      plastohydroquinone.

PMID- 15238274
TI  - Effect measures in prevalence studies.
AB  - There is still considerable confusion and debate about the appropriate methods
      for analyzing prevalence studies, and a number of recent papers have argued that
      prevalence ratios are the preferred method and that prevalence odds ratios should
      not be used. These arguments assert that the prevalence ratio is obviously the
      better measure and the odds ratio is "unintelligible." They have often been
      accompanied by demonstrations that when a disease is common the prevalence ratio
      and the prevalence odds ratio may differ substantially. However, this does not
      tell us which measure is the more valid to use. In fact, the prevalence odds
      ratio a) estimates the incidence rate ratio with fewer assumptions than are
      required for the prevalence ratio; b) can be estimated using the same methods as
      for the odds ratio in case-control studies, namely, the Mantel-Haenszel method
      and logistic regression; and c) provides practical, analytical, and theoretical
      consistency between analyses of a prevalence study and prevalence case-control
      analyses based on the same study population. For these reasons, the prevalence
      odds ratio will continue to be one of the standard methods for analyzing
      prevalence studies and prevalence case-control studies.

PMID- 15238275
TI  - An unrecognized source of PCB contamination in schools and other buildings.
AB  - An investigation of 24 buildings in the Greater Boston Area revealed that one
      third (8 of 24) contained caulking materials with polychlorinated biphenyl (PCB)
      content exceeding 50 ppm by weight, which is the U.S. Environmental Protection
      Agency (U.S. EPA) specified limit above which this material is considered to be
      PCB bulk product waste. These buildings included schools and other public
      buildings. In a university building where similar levels of PCB were found in
      caulking material, PCB levels in indoor air ranged from 111 to 393 ng/m3; and in
      dust taken from the building ventilation system, < 1 ppm to 81 ppm. In this
      building, the U.S. EPA mandated requirements for the removal and disposal of the
      PCB bulk product waste as well as for confirmatory sampling to ensure that the
      interior and exterior of the building were decontaminated. Although U.S. EPA
      regulations under the Toxic Substances Control Act stipulate procedures by which
      PCB-contaminated materials must be handled and disposed, the regulations
      apparently do not require that materials such as caulking be tested to determine
      its PCB content. This limited investigation strongly suggests that were this
      testing done, many buildings would be found to contain high levels of PCBs in the
      building materials and potentially in the building environment. The presence of
      PCBs in schools is of particular concern given evidence suggesting that PCBs are
      developmental toxins.

PMID- 15238277
TI  - Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain
      of juvenile largemouth bass.
AB  - Although nanotechnology has vast potential in uses such as fuel cells,
      microreactors, drug delivery devices, and personal care products, it is prudent
      to determine possible toxicity of nanotechnology-derived products before
      widespread use. It is likely that nanomaterials can affect wildlife if they are
      accidentally released into the environment. The fullerenes are one type of
      manufactured nanoparticle that is being produced by tons each year, and initially
      uncoated fullerenes can be modified with biocompatible coatings. Fullerenes are
      lipophilic and localize into lipid-rich regions such as cell membranes in vitro,
      and they are redox active. Other nano-sized particles and soluble metals have
      been shown to selectively translocate into the brain via the olfactory bulb in
      mammals and fish. Fullerenes (C60) can form aqueous suspended colloids (nC60);
      the question arises of whether a redox-active, lipophilic molecule could cause
      oxidative damage in an aquatic species. The goal of this study was to investigate
      oxyradical-induced lipid and protein damage, as well as impacts on total
      glutathione (GSH) levels, in largemouth bass exposed to nC60. Significant lipid
      peroxidation was found in brains of largemouth bass after 48 hr of exposure to
      0.5 ppm uncoated nC60. GSH was also marginally depleted in gills of fish, and
      nC60 increased water clarity, possibly due to bactericidal activity. This is the
      first study showing that uncoated fullerenes can cause oxidative damage and
      depletion of GSH in vivo in an aquatic species. Further research needs to be done
      to evaluate the potential toxicity of manufactured nanomaterials, especially with
      respect to translocation into the brain.

PMID- 15238276
TI  - Survivorship patterns of larval amphibians exposed to low concentrations of
      atrazine.
AB  - Amphibians can be exposed to contaminants in nature by many routes, but perhaps
      the most likely route is agricultural runoff in amphibian breeding sites. This
      runoff results in high-level pulses of pesticides. For example, atrazine, the
      most widely used pesticide in the United States, can be present at several parts
      per million in agricultural runoff. However, pesticide levels are likely to
      remain in the environment at low levels for longer periods. Nevertheless, most
      studies designed to examine the impacts of contaminants are limited to short-term
      (approximately 4 days) tests conducted at relatively high concentrations. To
      investigate longer-term (approximately 30 days) exposure of amphibians to low
      pesticide levels, we exposed tadpoles of four species of frogs--spring peepers
      (Pseudacris crucifer), American toads (Bufo americanus, green frogs (Rana
      clamitans), and wood frogs (Rana sylvatica)--at early and late developmental
      stages to low concentrations of a commercial preparation of atrazine (3, 30, or
      100 ppb; the U.S. Environmental Protection Agency drinking water standard is 3
      ppb). We found counterintuitive patterns in rate of survivorship. Survival was
      significantly lower for all animals exposed to 3 ppb compared with either 30 or
      100 ppb, except the late stages of B. americanus and R. sylvatica. These survival
      patterns highlight the importance of investigating the impacts of contaminants
      with realistic exposures and at various developmental stages. This may be
      particularly important for compounds that produce greater mortality at lower
      doses than higher doses, a pattern characteristic of many endocrine disruptors.

PMID- 15238278
TI  - Personal exposure to submicrometer particles and heart rate variability in human
      subjects.
AB  - We conducted a study on two panels of human subjects--9 young adults and 10
      elderly patients with lung function impairments--to evaluate whether
      submicrometer particulate air pollution was associated with heart rate
      variability (HRV). We measured these subjects' electrocardiography and personal
      exposure to number concentrations of submicrometer particles with a size range of
      0.02-1 microm (NC0.02-1) continuously during daytime periods. We used linear
      mixed-effects models to estimate the relationship between NC0.02-1 and log10
      transformed HRV, including standard deviation of all normal-to-normal intervals
      (SDNN), square root of the mean of the sum of the squares of differences between
      adjacent NN intervals (r-MSSD), low frequency (LF, 0.04-0.15 Hz), and high
      frequency (HF, 0.15-0.40 Hz), adjusted for age, sex, body mass index, tobacco
      exposure, and temperature. For the young panel, a 10,000-particle/cm3) increase
      in NC0.02-1 with 1-4 hr moving average exposure was associated with 0.68-1.35%
      decreases in SDNN, 1.85-2.58% decreases in r-MSSD, 1.32-1.61% decreases in LF,
      and 1.57-2.60% decreases in HF. For the elderly panel, a 10,000-particle/cm3
      increase in NC0.02-1 with 1-3 hr moving average exposure was associated with 1.72
      3.00% decreases in SDNN, 2.72-4.65% decreases in r-MSSD, 3.34-5.04% decreases in
      LF, and 3.61-5.61% decreases in HF. In conclusion, exposure to NC0.02-1 was
      associated with decreases in both time-domain and frequency-domain HRV indices in
      human subjects.

PMID- 15238279
TI  - Community-based randomized double-blind study of gastrointestinal effects and
      copper exposure in drinking water.
AB  - We assessed gastrointestinal effects in 1,365 adults exposed to either < 0.01
      (controls), 2, 4, or 6 mg copper/L of drinking water for 2 months in a
      randomized, double-blind community-based study. The risk of symptoms increased
      with increasing Cu exposure and decreased with time. The best model by counting
      process analysis included Cu concentration and sex. The risk of symptoms remained
      significantly higher in women than in men during weeks 1-4 for all concentrations
      tested; at week 1 comparison with the < 0.01-mg/L group showed that differences
      became significant in women at 4 mg/L [relative risk (RR) = 1.53; 95% confidence
      interval (CI), 1.02-2.05), and in men at 6 mg/L (RR = 1.9; 95% CI, 1.02-2.79). At
      week 2 for men and week 4 in women, the Cu concentration required to obtain
      significant differences on symptom report was > 6 mg Cu/L. We conclude that
      exposure to Cu in drinking water results in gastrointestinal symptoms, which are
      modulated by Cu concentration, time, and sex.

PMID- 15238280
TI  - Associations between organochlorine contaminant concentrations and clinical
      health parameters in loggerhead sea turtles from North Carolina, USA.
AB  - Widespread and persistent organochlorine (OC) contaminants, such as
      polychlorinated biphenyls (PCBs) and pesticides, are known to have broad-ranging
      toxicities in wildlife. In this study we investigated, for the first time, their
      possible health effects on loggerhead sea turtles (Caretta caretta). Nonlethal
      fat biopsies and blood samples were collected from live turtles for OC
      contaminant analysis, and concentrations were compared with clinical health
      assessment data, including hematology, plasma chemistry, and body condition.
      Concentrations of total PCBs (Sigma PCBs), Sigma DDTs, Sigma chlordanes,
      dieldrin, and mirex were determined in 44 fat biopsies and 48 blood samples.
      Blood concentrations of Sigma chlordanes were negatively correlated with red
      blood cell counts, hemoglobin, and hematocrit, indicative of anemia. Positive
      correlations were observed between most classes of OC contaminants and white
      blood cell counts and between mirex and Sigma TCDD-like PCB concentrations and
      the heterophil:lymphocyte ratio, suggesting modulation of the immune system. All
      classes of OCs in the blood except dieldrin were correlated positively with
      aspartate aminotransferase (AST) activity, indicating possible hepatocellular
      damage. Mirex and Sigma TCDD-like PCB blood concentrations were negatively
      correlated with alkaline phosphatase (ALP) activity. Significant correlations to
      levels of certain OC contaminant classes also suggested possible alteration of
      protein (increasing blood urea nitrogen, decreasing albumin:globulin ratio),
      carbohydrate (decreasing glucose), and ion (increasing sodium, decreasing
      magnesium) regulation. These correlations suggest that OC contaminants may be
      affecting the health of loggerhead sea turtles even though sea turtles accumulate
      lower concentrations of OCs compared with other wildlife.

PMID- 15238281
TI  - Associations between plasma DDE levels and immunologic measures in African
      American farmers in North Carolina.
AB  - Experimental studies in rodents demonstrate evidence of immunosuppressive effects
      of dietary exposure to DDT [2,2-bis((italic)p(/italic)-chlorophenyl)-1,1,1
      trichloroethane], but human data pertaining to immunomodulating effects of DDT
      exposure are limited. In this study we examined the association between the
      persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p
      chlorophenyl)ethylene p,p'-DDE) and immunologic measures using blood samples in a
      relatively highly exposed population of farmers in the United States. Levels of
      serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies
      in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African
      American male farmers (30-88 years of age; median, 64 years). Participants were
      recruited through black churches in four rural counties in eastern North
      Carolina. Data collection included a telephone interview pertaining to farming
      practices and health history, and one blood sample was collected from each
      participant. Linear and logistic regression, adjusting for age, cholesterol,
      triglycerides, smoking status, and years of any kind of pesticide use, was used
      to assess the association between immunologic parameters and plasma levels of
      p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 microg/L (range, 0.6
      77.4 microg/L). There was no association between p,p'-DDE and IgA in any of the
      models. IgG levels decreased with increasing p,p'-DDE levels, with a
      statistically significant decrease of approximately 50% in the highest two
      categories of exposure (greater than or equal to 6.0 microg/L) compared with
      values of < 3.0 microg/L. Sixteen (12%) were positive for antinuclear antibodies.
      The prevalence of antinuclear antibodies was somewhat elevated in the highest
      category of p,p'-DDE exposure (odds ratio, 1.9; 95% confidence interval, 0.32
      11.3; for > or = 12.0 microg/L compared with < 3.0 microg/L p,p'-DDE), but this
      difference was not statistically significant. These analyses provide evidence
      that p,p'-DDE modulates immune responses in humans.

PMID- 15238282
TI  - Different levels of polybrominated diphenyl ethers (PBDEs) and chlorinated
      compounds in breast milk from two U.K. Regions.
AB  - Polybrominated diphenyl ether (PBDE) congeners are constituents of flame
      retardants, and there is growing concern regarding their persistence,
      bioaccumulation, and toxicity. We collected breast milk samples between late 2001
      and early 2003 from 54 U.K.-resident mothers. Of these, 27 originated from
      southeast England (London), and the other 27 originated from northwest England
      (Lancaster). Analysis of milk-fat extracts by gas chromatography-mass
      spectrometry was performed to determine the levels of 15 PBDE congeners, 15
      polychlorinated biphenyl (PCB) congeners, and other selected chlorinated
      compounds. PCB and organochlorine (OC) levels in southeast samples were
      consistently higher, and significant differences (p < 0.05) were observed. Sigma
      PBDE levels ranged from 0.3 to 69 ng/g lipid (geometric mean, 6.6 ng/g), and PBDE
      47 was the most abundant congener. Sigma PCB levels ranged from 26 to 530 ng/g
      lipid (geometric mean, 150 ng/g) and were composed mainly of PCB-153 (26%), PCB
      138 (20%), and PCB-180 (13%). OC levels for 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane (p,p'-DDT) and its metabolites (Sigma DDX) ranged from 24 to
      2,300 ng/g lipid (geometric mean, 160 ng/g);Sigma hexachlorocyclohexane levels
      ranged from 1.2 to 1,500 ng/g lipid (geometric mean, 16 ng/g). Using nuclear
      magnetic resonance-based metabonomics, samples (n = 7) containing the highest
      contaminant levels were compared with samples (n = 7) containing the lowest
      levels. Excellent separation along the first principal component implied that the
      chemical constituents of the two groups were significantly different. Although
      reasons for such differences remain obscure, lifestyle factors associated with a
      more heterogeneous London cohort could be responsible. Identifying primary routes
      of contaminant exposures and their biologic effects is of great importance. Key
      words: breast milk, flame retardants, gas chromatography-mass spectrometry, milk
      fat extracts, organochlorines, PBDE-47, persistent contaminants, polybrominated
      diphenyl ethers, polychlorinated biphenyls, United Kingdom.

PMID- 15238283
TI  - Unhealthy landscapes: Policy recommendations on land use change and infectious
      disease emergence.
AB  - Anthropogenic land use changes drive a range of infectious disease outbreaks and
      emergence events and modify the transmission of endemic infections. These drivers
      include agricultural encroachment, deforestation, road construction, dam
      building, irrigation, wetland modification, mining, the concentration or
      expansion of urban environments, coastal zone degradation, and other activities.
      These changes in turn cause a cascade of factors that exacerbate infectious
      disease emergence, such as forest fragmentation, disease introduction, pollution,
      poverty, and human migration. The Working Group on Land Use Change and Disease
      Emergence grew out of a special colloquium that convened international experts in
      infectious diseases, ecology, and environmental health to assess the current
      state of knowledge and to develop recommendations for addressing these
      environmental health challenges. The group established a systems model approach
      and priority lists of infectious diseases affected by ecologic degradation.
      Policy-relevant levels of the model include specific health risk factors,
      landscape or habitat change, and institutional (economic and behavioral) levels.
      The group recommended creating Centers of Excellence in Ecology and Health
      Research and Training, based at regional universities and/or research institutes
      with close links to the surrounding communities. The centers' objectives would be
      3-fold: a) to provide information to local communities about the links between
      environmental change and public health; b) to facilitate fully interdisciplinary
      research from a variety of natural, social, and health sciences and train
      professionals who can conduct interdisciplinary research; and c) to engage in
      science-based communication and assessment for policy making toward sustainable
      health and ecosystems.

PMID- 15238284
TI  - Adverse health effects of chronic exposure to low-level cadmium in foodstuffs and
      cigarette smoke.
AB  - Cadmium is a cumulative nephrotoxicant that is absorbed into the body from
      dietary sources and cigarette smoking. The levels of Cd in organs such as liver
      and kidney cortex increase with age because of the lack of an active biochemical
      process for its elimination coupled with renal reabsorption. Recent research has
      provided evidence linking Cd-related kidney dysfunction and decreases in bone
      mineral density in nonoccupationally exposed populations who showed no signs of
      nutritional deficiency. This challenges the previous view that the concurrent
      kidney and bone damage seen in Japanese itai-itai disease patients was the result
      of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and
      calcium. Further, such Cd-linked bone and kidney toxicities were observed in
      people whose dietary Cd intakes were well within the provisional tolerable weekly
      intake (PTWI) set by the Joint Food and Agriculture Organization/World Health
      Organization Expert Committee on Food Additives of 1 microg/kg body weight/day or
      70 microg/day. This evidence points to the much-needed revision of the current
      PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is
      accumulating and Cd effects on reproductive outcomes have begun to emerge.

PMID- 15238285
TI  - Nutritional factors and susceptibility to arsenic-caused skin lesions in West
      Bengal, India.
AB  - There has been widespread speculation about whether nutritional deficiencies
      increase the susceptibility to arsenic health effects. This is the first study to
      investigate whether dietary micronutrient and macronutrient intake modulates the
      well-established human risk of arsenic-induced skin lesions, including
      alterations in skin pigmentation and keratoses. The study was conducted in West
      Bengal, India, which along with Bangladesh constitutes the largest population in
      the world exposed to arsenic from drinking water. In this case-control study
      design, cases were patients with arsenic-induced skin lesions and had < 500
      microg/L arsenic in their drinking water. For each case, an age- and sex-matched
      control was selected from participants of a 1995-1996 cross-sectional survey,
      whose drinking water at that time also contained < 500 microg/L arsenic.
      Nutritional assessment was based on a 24-hr recall for major dietary constituents
      and a 1-week recall for less common constituents. Modest increases in risk were
      related to being in the lowest quintiles of intake of animal protein [odds ratio
      (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95%
      CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95%
      CI, 0.87-3.2). Conditional logistic regression suggested that the strongest
      associations were with low calcium, low animal protein, low folate, and low fiber
      intake. Nutrient intake was not related to arsenic exposure. We conclude that low
      intake of calcium, animal protein, folate, and fiber may increase susceptibility
      to arsenic-caused skin lesions. However, in light of the small magnitude of
      increased risks related to these dietary deficiencies, prevention should focus on
      reducing exposure to arsenic.

PMID- 15238286
TI  - Blood lead secular trend in a cohort of children in Mexico City (1987-2002).
AB  - We determined the secular trend in blood lead levels in a cohort of 321 children
      born in Mexico City between 1987 and 1992. Blood lead level was measured every 6
      months during a 10-year period. We modeled the effect of yearly air lead
      concentration nested within the calendar year in which the child was born, family
      use of lead-glazed pottery, socioeconomic status, year in which the child was
      born, age of the child at the time of blood lead measurement, place of residence,
      and an indicator variable for subjects with complete or incomplete blood lead
      values. The yearly mean of air lead of the Valley of Mexico decreased from its
      highest level of 2.80 microg/m3 in 1987 to 0.07 microg/m3 in 2002. The
      contribution of air lead to blood lead according to year of birth was strongest
      for subjects born in 1987 and fell to nearly zero for children born in 1992. The
      geometric mean of the entire cohort rose from 8.4 microg/dL in the first year of
      life to 10.1 microg/dL in the second and decreased thereafter until it reached
      6.4 microg/dL at 10 years of age. Children of families who used lead-glazed
      ceramics had blood lead levels 18.5% higher than did children of nonusing
      families. Children who belonged to the lowest socioeconomic levels had blood lead
      levels 32.2% higher than did those of highest socioeconomic levels. Children who
      lived in the northeast part of the city had blood lead levels 10.9% higher
      compared with those who lived in the southwest.

PMID- 15238287
TI  - Association of in utero organophosphate pesticide exposure and fetal growth and
      length of gestation in an agricultural population.
AB  - Although pesticide use is widespread, little is known about potential adverse
      health effects of in utero exposure. We investigated the effects of
      organophosphate pesticide exposure during pregnancy on fetal growth and
      gestational duration in a cohort of low-income, Latina women living in an
      agricultural community in the Salinas Valley, California. We measured nonspecific
      metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and
      metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos
      [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4
      nitrophenol) in maternal urine collected twice during pregnancy. We also measured
      levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in
      maternal and umbilical cord blood. We failed to demonstrate an adverse
      relationship between fetal growth and any measure of in utero organophosphate
      pesticide exposure. In fact, we found increases in body length and head
      circumference associated with some exposure measures. However, we did find
      decreases in gestational duration associated with two measures of in utero
      pesticide exposure: urinary dimethyl phosphate metabolites [beta(adjusted) = 
      0.41 weeks per log10 unit increase; 95% confidence interval (CI), -0.75 -- -0.02;
      p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as
      malathion, and umbilical cord cholinesterase (beta(adjusted) = 0.34 weeks per
      unit increase; 95% CI, 0.13-0.55; p = 0.001). Shortened gestational duration was
      most clearly related to increasing exposure levels in the latter part of
      pregnancy. These associations with gestational age may be biologically plausible
      given that organophosphate pesticides depress cholinesterase and acetylcholine
      stimulates contraction of the uterus. However, despite these observed
      associations, the rate of preterm delivery in this population (6.4%) was lower
      than in a U.S. reference population.

PMID- 15238288
TI  - Prenatal insecticide exposures and birth weight and length among an urban
      minority cohort.
AB  - We reported previously that insecticide exposures were widespread among minority
      women in New York City during pregnancy and that levels of the organophosphate
      chlorpyrifos in umbilical cord plasma were inversely associated with birth weight
      and length. Here we expand analyses to include additional insecticides (the
      organophosphate diazinon and the carbamate propoxur), a larger sample size (n =
      314 mother-newborn pairs), and insecticide measurements in maternal personal air
      during pregnancy as well as in umbilical cord plasma at delivery. Controlling for
      potential confounders, we found no association between maternal personal air
      insecticide levels and birth weight, length, or head circumference. For each log
      unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6
      g [95% confidence interval (CI), -81.8 to -3.8, p = 0.03] and birth length
      decreased by 0.24 cm (95% CI, -0.47 to -0.01, p = 0.04). Combined measures of
      (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were
      also inversely associated with birth weight and length (p < 0.05). Birth weight
      averaged 186.3 g less (95% CI, -375.2 to -45.5) among newborns with the highest
      compared with lowest 26% of exposure levels (p = 0.01). Further, the associations
      between birth weight and length and cord plasma chlorpyrifos and diazinon were
      highly significant (p < or = 0.007) among newborns born before the 2000-2001 U.S.
      Environmental Protection Agency's regulatory actions to phase out residential use
      of these insecticides. Among newborns born after January 2001, exposure levels
      were substantially lower, and no association with fetal growth was apparent (p >
      0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely
      associated with birth length, a finding of borderline significance (p = 0.05)
      after controlling for chlorpyrifos and diazinon. Results indicate that prenatal
      chlorpyrifos exposures have impaired fetal growth among this minority cohort and
      that diazinon exposures may have contributed to the effects. Findings support
      recent regulatory action to phase out residential uses of the insecticides.

PMID- 15238289
TI  - Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility
      to procarcinogenic DNA damage.
AB  - Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are
      widespread air contaminants released by transportation vehicles, power
      generation, and other combustion sources. Experimental evidence indicates that
      the developing fetus is more susceptible than the adult to carcinogenic effects
      of PAHs, although laboratory studies in rodents suggest that the dose to fetal
      tissues is an order of magnitude lower than that to maternal tissues. To assess
      fetal versus adult susceptibility to PAHs and environmental tobacco smoke (ETS),
      we compared carcinogen-DNA adducts (a biomarker associated with increased cancer
      risk) and cotinine (a biomarker of tobacco smoke exposure) in paired blood
      samples collected from mothers and newborns in New York City. We enrolled 265
      nonsmoker African-American and Latina mother-newborn pairs in New York City
      between 1997 and 2001 (estimated average ambient air BaP concentrations < 0.5
      ng/m3). Despite the estimated 10-fold lower fetal dose, mean levels of BaP-DNA
      adducts as determined by high-performance liquid chromatography-fluorescence were
      comparable in paired New York City newborn and maternal samples (0.24 adducts per
      10(8) nucleotides, 45% of newborns with detectable adducts vs. 0.22 per 10(8)
      nucleotides, 41% of mothers with detectable adducts). However, by the Wilcoxon
      signed-rank test, the levels in newborns were higher (p = 0.02). Mean cotinine
      was higher in newborns than in mothers (1.7 ng/mL, 47% detectable vs. 1.28 ng/mL,
      44% detectable). Consistent with our prior study in a Caucasian Polish
      population, these results indicate increased susceptibility of the fetus to DNA
      damage and reduced ability to clear ETS constituents. The findings have
      implications for risk assessment, given the need to protect children as a
      sensitive subset of the population.

PMID- 15238290
TI  - Fertilizers, water quality, and human health.

PMID- 15238291
TI  - Endosulfan's effects: omissions and flawed data.

PMID- 15238292
TI  - Endosulfan's effects: inaccurate data.

PMID- 15238294
TI  - Defining wetlands.

PMID- 15238298
TI  - Global nitrogen: cycling out of control.

PMID- 15238295
TI  - Phthalate exposure and early thelarche.

PMID- 15238299
TI  - Chicken electronics: a technology plucked from waste.

PMID- 15238301
TI  - Heart rate variability and particulate exposure in vehicle maintenance workers: a
      pilot study.
AB  - The association between occupational exposure to PM(2.5) and heart rate
      variability was investigated in a repeated measures, longitudinal study of
      vehicle maintenance workers occupationally exposed to automobile emissions. Five
      subjects were monitored for occupational exposure to fine particulate matter
      (PM(2.5)) on 6 workdays using an aerosol photometer, validated with side-by-side
      sampling with a gravimetric method. End-of-day heart rate variability statistics
      were derived using short-term electrocardiogram recordings for each participant.
      Workplace carbon monoxide and outdoor, ambient fine particulate matter were also
      monitored. Regression statistics were used to investigate associations between
      same-day PM(2.5) levels and heart rate variability statistics using mixed-effects
      multiple regression of pooled data. No statistically significant associations
      were observed between occupational PM(2.5) and measures of heart rate
      variability. A statistically significant increase in total spectral power was
      associated with ambient PM(2.5) (p < 0.05). The data suggest a threshold below
      which no degradation in cardiac autonomic control of healthy workers occurs when
      challenged by occupational PM(2.5) exposure. This study was limited in
      population, exposure level, and type of particulate exposures. Additional studies
      are recommended on broader occupational populations.

PMID- 15238302
TI  - Culturability and toxicity of sick building syndrome-related fungi over time.
AB  - Two experiments were conducted regarding the culturability and toxicity of fungi
      located on building materials over time and the efficacy of seven laboratory
      techniques in recovering culturable fungi from sample swabs. In the first
      experiment, eight sections of drywall were inoculated with Stachybotrys chartarum
      and stored at 25 +/- 5 degrees Celsius and 20-60% relative humidity (RH) for up
      to two years. Another eight sections of ceiling tile were stored at 100% RH for 1
      year. Six sections of ceiling tile and 15 swabs were also inoculated with
      Penicillium chrysogenum and S. chartarum respectively and stored under the same
      conditions for 8 months and 3.3 years. All materials were tested for
      culturability at the end of the storage period. S. chartarum-inoculated samples
      were also tested for toxicity. In the second experiment (replicated twice), S.
      chartarum and Chaetomium globosum were inoculated onto 84 swabs each. Storage was
      up to 266 days at 25 +/- 5 degrees Celsius and 20-60% RH. Seven techniques were
      compared regarding the recovery of culturable fungi from the swabs over different
      time points. Results for Experiment 1 showed that all samples were culturable
      after the storage period and that the S. chartarum-inoculated drywall samples
      were toxic. In Experiment 2, all techniques showed high rates of recovery. These
      data show that despite being without a water source, these organisms can be
      culturable and toxic after long periods of time under conditions similar to human
      occupied dwellings and that a number of preparation techniques are suitable for
      the recovery of these fungi from inoculated swabs.

PMID- 15238303
TI  - Personal exposures to inorganic and organic dust in manual harvest of California
      citrus and table grapes.
AB  - The aim of this study was to determine characteristics of personal exposure to
      inorganic and organic dust during manual harvest operations of California citrus
      and table grapes. Personal exposures to inhalable dust and respirable dust were
      measured five times over a 4-month period of harvesting season. We analyzed
      components of the dust samples for mineralogy, respirable quartz, endotoxin, and
      total and culturable microorganisms. Workers manually harvesting were exposed to
      a complex mixture of inorganic and organic dust. Exposures for citrus harvest had
      geometric means of 39.7 mg/m(3) for inhalable dust and 1.14 mg/m(3) for
      respirable dust. These exposures were significantly higher than those for table
      grape operations and exceeded the threshold limit value for inhalable dust and
      respirable quartz. Exposures for table grape operations were lower than the
      threshold limit value, except inhalable dust exposure during leaf pulling.
      Considered independently, exposures to inhalable dust and respirable quartz in
      citrus harvest may be high enough to cause respiratory health effects. The degree
      of vigorous contact with foliage appeared to be a significant determining factor
      of exposures in manual harvesting.

PMID- 15238304
TI  - A field method for near real-time analysis of perchloroethylene in end-exhaled
      breath.
AB  - The field method for near real-time analysis of perchloroethylene (Perc) in
      breath is simple, fast, and reproducible for Perc breath analysis in field
      settings and should prove useful in industrial hygiene practice. The method
      allows Perc monitoring with good specificity to the sub-part per million (ppm)
      level within minutes of exposure. A commercially available, portable gas
      chromatograph with a photoionization detector was used in these analyses. Gas
      chromatograph settings were optimized in the laboratory for measurement of Perc
      in Tedlar bags. Laboratory development of the method included evaluation of the
      sensitivity, specificity, precision, and speed of analysis for Perc. Replicate
      aliquots of Perc at concentrations ranging from 0.01 to 100 ppm were used to
      construct a calibration curve. The mean retention time for Perc was 238 sec. The
      impact of potential interference by acetone, toluene, isoprene, methanol,
      ethanol, acetaldehyde, carbon tetrachloride, benzene, or chloroform was evaluated
      by mixing Perc with each compound and performing analyses. Measurements of Perc
      in human breath samples collected in Tedlar bags in a workplace setting were made
      and compared to measurements of the same samples made by an established
      analytical method using charcoal tubes (National Institute of Occupational Safety
      and Health [NIOSH] Method 1003). The accuracy, precision, and speed of the gas
      chromatograph method were determined. Measurements made with the new method were
      within a margin of +/- 8.8% (95% CI, n = 6) of measurements made according to
      NIOSH Method 1003 for field samples in the range of 0.9 to 6 ppm. Method
      precision was determined by calculating the pooled coefficient of variation for
      all measurements (replicates = 3) made in the field and was found to be 5.8%.

PMID- 15238305
TI  - Active versus passive cooling during work in warm environments while wearing
      firefighting protective clothing.
AB  - This study examined whether active or passive cooling during intermittent work
      reduced the heat strain associated with wearing firefighting protective clothing
      (FPC) and self-contained breathing apparatus (SCBA) in the heat (35 degrees
      Celsius, 50% relative humidity). Fifteen male Toronto firefighters participated
      in the heat-stress trials. Subjects walked at 4.5 km.h(-1) with 0% elevation on
      an intermittent work (50 min) and rest (30 min) schedule. Work continued until
      rectal temperature (T(re)) reached 39.5 degrees Celsius, or heart rate (HR)
      reached 95% of maximum or exhaustion. One of three cooling strategies, forearm
      submersion (FS), mister (M), and passive cooling (PC) were employed during the
      rest phases. Tolerance time (TT) and total work time (WT) (min) were
      significantly increased during FS (178.7 +/- 13.0 and 124.7 +/- 7.94,
      respectively) and M (139.1 +/- 8.28 and 95.1 +/- 4.96, respectively), compared
      with PC (108.0 +/- 3.59 and 78.0 +/- 3.59). Furthermore, TT and WT were
      significantly greater in FS compared with M. Rates of T(re) increase, HR and T
      (sk) were significantly lower during active compared with passive cooling. In
      addition, HR and T(re) values in FS were significantly lower compared with M
      after the first rest phase. During the first rest phase, T(re) dropped
      significantly during FS (approximately 0.4 degree Celsius) compared with M
      (approximately 0.08 degree Celsius) while PC increased (approximately 0.2 degree
      Celsius). By the end of the second rest period T(re) was 0.9 degree Celsius lower
      in FS compared with M. The current findings suggest that there is a definite
      advantage when utilizing forearm submersion compared with other methods of active
      or passive cooling while wearing FPC and SCBA in the heat.

PMID- 15238306
TI  - Noise exposure and hearing loss among sand and gravel miners.
AB  - The objectives of this study were to describe workplace noise exposures, risk
      factors for hearing loss, and hearing levels among sand and gravel miners, and to
      determine whether full shift noise exposures resulted in changes in hearing
      thresholds from baseline values. Sand and gravel miners (n = 317) were
      interviewed regarding medical history, leisure-time and occupational noise
      exposure, other occupational exposures, and use of hearing protection.
      Audiometric tests were performed both before the work shift (following a 12-hour
      noise-free interval) and immediately following the work shift. Full shift noise
      dosimetry was conducted. Miners' noise exposures exceeded the Recommended
      Exposure Limit (REL) of the National Institute for Occupational Safety and Health
      (NIOSH) for 69% of workers, and exceeded the Mine Safety and Health
      Administration's action level for enrollment in a hearing conservation program
      for 41% of workers. Significantly higher noise exposures occurred among employees
      of small companies, among workers with a job classification of truck driver,
      among males, and among black workers. Hearing protection usage was low, with 48%
      of subjects reporting that they never used hearing protection. Hearing
      impairment, as defined by NIOSH, was present among 37% of 275 subjects with valid
      audiograms. Black male workers and white male workers had higher hearing
      thresholds than males from a comparison North Carolina population unexposed to
      industrial noise. Small but statistically significant changes in hearing
      thresholds occurred following full shift noise exposure among subjects who had
      good hearing sensitivity at baseline. In a logistic regression model, age and
      history of a past noisy job were significant predictors of hearing impairment.
      Overall, sand and gravel workers have excessive noise exposures and significant
      hearing loss, and demonstrate inadequate use of hearing protection. Well-designed
      hearing conservation programs, with reduction of noise exposure, are clearly
      needed.

PMID- 15238307
TI  - Predictors of work-related injuries and illnesses: national survey findings.
AB  - This study used national survey data of working adults (aged 33-41) to identify
      factors associated with the occurrence of occupational injuries and illnesses.
      Data from the National Longitudinal Survey of Youth were used to compare selected
      employment and personal characteristics for respondents who reported experiencing
      a work-related injury or illness with those who did not. Multivariate analyses
      were performed to calculate nationally representative odds ratios reflecting the
      likelihood for specific individual attributes and job characteristics to be
      associated with the reporting of a work-related injury or illness, while
      controlling for relevant covariates. In this study the incidence of occupational
      injuries was related to several demographic factors, including low family income
      and rural residence, and several job characteristics, including working in a high
      hazard occupation, job dissatisfaction, and exposure to six specific hazardous
      job activities: (1) performing lots of physical effort on the job, (2) lifting or
      carrying more than 10 lbs, (3) using stairs and inclines, (4) kneeling or
      crouching, (5) reaching, and (6) hearing special sounds. These results suggest
      targeted prevention strategies for decreasing the incidence of work-related
      injuries and illnesses, such as worker self-assessment of the total physical
      effort demanded by a job and periodic monitoring of workforce job satisfaction.

PMID- 15238308
TI  - Incidence of acute low-back injury among older workers in a cohort of material
      handlers.
AB  - Injuries to the low back are the most common cause for injury claims among
      material handlers. Previous studies have shown conflicting results about how age
      affects risk of low-back injury. This study describes the incidence of acute low
      back injury by age, gender, length of employment, and lifting intensity measured
      by job classification in a cohort of material handlers. The cohort included all
      material handlers employed at a large home improvement retail chain in California
      from 1989 through 1994. The cohort accrued approximately 50,000 full time
      equivalents over the study period. A total of 2152 low-back injuries were
      reported during the study period. Compared to workers aged younger than 45, the
      crude rate ratio for workers aged 45 to 54 was 0.78, and for workers aged 55 and
      above was 0.84. However, this age difference was not apparent among length of
      employment strata or among jobs with low or medium lifting intensity. A higher
      proportion of workers over the age of 55 missed work time because of their
      injury, and workers over 45 had a higher average number of lost workdays per
      injury. This research indicates that workers over age 55 had similar injury rates
      to workers younger than age 55, even when considering lifting intensity and
      length of employment. However, their injuries may cause a longer period of
      disability.

PMID- 15238311
TI  - Development of evaluation procedures for local exhaust ventilation for United
      States postal service mail-processing equipment.
AB  - Researchers from the National Institute for Occupational Safety and Health
      (NIOSH) have conducted several evaluations of local exhaust ventilation (LEV)
      systems for the United States Postal Service (USPS) since autumn 2001 when (a)
      terrorist(s) employed the mail system for acts of bioterrorism. As a part of the
      USPS 2002 Emergency Preparedness Plan, the development and installation of LEV
      onto USPS mail-processing equipment can reduce future exposures to operators from
      potentially hazardous contaminants, such as anthrax, which might be emitted
      during the processing of mail. This article describes how NIOSH field testing led
      to the development of recommended testing procedures for evaluations of LEV
      capture efficiency for mail-processing equipment, including tracer gas
      measurements, smoke release observations, air velocity measurements, and decay
      rate testing under access hoods.

PMID- 15238312
TI  - UV-induced inactivation rates for airborne Mycobacterium bovis BCG.
AB  - Engineering ultraviolet irradiation systems as a control against infectious
      airborne diseases requires a knowledge of intrinsic ultraviolet (UV) inactivation
      rates of airborne bacteria. Ultraviolet inactivation rates for airborne
      Mycobacterium bovis bacillus Calmette-Guerin (BCG) were determined at 50% and 95%
      relative humidity (RH) in a 0.8 m3 bioaerosol reactor. Ultraviolet inactivation
      response of waterborne M. bovis BCG pure cultures was also determined. At 50% RH
      the airborne UV inactivation rates observed were two times greater than those
      observed in saturated air (RH = 95%), and rates at 95% RH were similar to those
      observed in otherwise identical cultures suspended in water. Intrinsic UV
      inactivation rates for M. bovis BCG were statistically similar to rates observed
      for Mycobacterium parafortuitum at 50% and 95% RH, indicating that M.
      parafortuitum is a valid surrogate for studying airborne UV responses of M. bovis
      BCG and Mycobacterium tuberculosis. Results also confirm that UV inactivation
      responses for bacteria suspended in water cannot be used to estimate UV dose
      response in unsaturated air.

PMID- 15238313
TI  - Imputation of data values that are less than a detection limit.
AB  - Results of the analyses of occupational and environmental samples are frequently
      reported as "less than a specified value," a practice followed by many analytical
      laboratories. A left-censored distribution occurs when analytical laboratories do
      not report results that fall below their limits of detection or quantification.
      Approximately 37% of the household interior dust lead loadings collected in a
      large-scale, multisite, longitudinal study of lead-based paint hazard controls
      were reported to be below the "method detection limit." These unreported values
      are unusable in any statistical analysis of the data and must be replaced by a
      valid dust lead loading estimate, a process called data imputation. This
      investigation tested how well data imputed using a newly formulated procedure for
      estimating the data below the method detection limit were correlated with dust
      lead loadings reported by the participating laboratories after special request.
      These results were also compared with those obtained by imputing the minimum
      detectable level by the square root of 2. Imputation of the low lead loadings was
      accomplished by substituting the value associated with the median percentile
      below each laboratory's method detection limit. A correlation of r = 0.50 was
      calculated between the predicted and reported dust lead loadings, with only
      slight bias (2.9%) in the predicted values. An alternative imputation procedure
      that used the predicted value from structural equation models fit to the
      noncensored dust lead loadings performed about as well, although the predictions
      had to be "centered" to correspond to the censored data. An estimator that
      combined both of these imputation procedures only slightly improved the
      correlation between the predicted and laboratory values (r = 0.51). These results
      support the use of the new procedure rather than the commonly used imputed values
      of the method detection limit divided by 2 or by the square root of 2. Imputing
      values based on either of these common approaches may result in much more biased
      predictions for the censored data; in the case of these data, the dust lead
      loadings were overestimated by 348%. The results also suggest that analytical
      laboratories should provide a numerical result for all analyzed samples, with a
      "flag" of those values below their detection limit, since these results may be
      more accurate than any imputed value, particularly those provided by the commonly
      used method of dividing the minimum detection limit by the square root of 2.

PMID- 15238314
TI  - An investigation into techniques for cleaning mold-contaminated home contents.
AB  - This study examined the efficacy of the following treatments to reduce selected
      fungal spore and mycotoxin levels on materials commonly found in home contents:
      (1) gamma irradiation at a 10-13 kiloGray exposure, (2) a detergent/bleach wash,
      and (3) a steam cleaning technique. A minimum of six replicates were performed
      per treatment. Paper, cloth, wood, and carpet were inoculated with either fungal
      spores (Stachybotrys chartarum, Aspergillus niger, Penicillium chrysogenum, or
      Chaetomium globosum) at 240,000 spores/2.54 cm2 of material or with the
      mycotoxins roridin A, T-2, and verrucarin A at 10 microg per 2.54 cm2 of
      material. Treatments were evaluated with an agar plating technique for fungal
      spores and a yeast toxicity culture assay for mycotoxins. Results showed that
      gamma irradiation inactivated fungal spores, but the treatment was not successful
      in inactivating mycotoxins. The washing technique completely inactivated or
      removed spores on all materials except for C. globosum, which was reduced on all
      items except paper (p < 0.05). Washing inactivated all mycotoxins on paper and
      cloth but not on carpet or untreated wood (p < 0.001). The steam cleaning
      treatment did not completely eliminate any fungal spores; however, it reduced P.
      chrysogenum numbers on all materials, C. globosum was reduced on wood and carpet,
      and S. chartarum was reduced on wood (p < 0.05). Steam cleaning was unsuccessful
      in inactivating any of the tested mycotoxins. These results show that the
      bleach/detergent washing technique was more effective overall in reducing spore
      and mycotoxin levels than gamma irradiation or steam cleaning. However, the other
      examined techniques were successful in varying degrees.

PMID- 15238315
TI  - Preparing employers to implement the Washington state ergonomics rule: evaluation
      of the training workshops.
AB  - Training of managers and workers is a mainstay of health and safety practice but
      it is rarely evaluated. We assessed the change in knowledge and perceived
      competence of participants, regarding the Washington State Ergonomics Rule, with
      the implementation of a 4-hour training session. We used the before and after
      study design without a control group to evaluate training workshops conducted
      between April 2001 and August 2002. There were 511 participants involved in the
      evaluation. Overall, participants' knowledge of the ergonomics rule and hazard
      reduction methods increased significantly. Those with no previous ergonomics
      training had a greater increase in their knowledge than those who had some
      ergonomics training in the past.

PMID- 15238316
TI  - Limitations of using dosimeters in impulse noise environments.
AB  - The National Institute for Occupational Safety and Health (NIOSH) investigated
      the capabilities of noise dosimeters to measure personal exposure to impulse
      noise. The two leading types of commercially available dosimeters were evaluated
      in terms of their ability to measure and integrate impulses generated from
      gunfire during live-fire exercises at a law enforcement indoor firing range.
      Sound measurements were conducted throughout the firing range using dosimeters,
      sound level meters, and a measurement configuration that consisted of a quarter
      inch microphone and a digital audiotape recorder to capture the impulse
      waveforms. Personal dosimetry was conducted on eight shooters, an observer, and
      the range master. Peak levels from gunfire reached 163 decibels (dB), exceeding
      the nominal input limit of the dosimeters. The dosimeters "clipped" the impulses
      by acting as if the gunfire had a maximum level of 146 dB. In other cases,
      however, peak levels (e.g., 108 dB) were below the dosimeter input limits, but
      the dosimeters still showed a peak level of 146 dB. Although NIOSH recommends
      that sound levels from 80 to 140 dB (A-weighted) be integrated in the calculation
      of dose and the time-weighted average, our present data suggest this criterion
      may be inadequate. These results showed that some instruments are incapable of
      providing accurate measures of impulse sounds because of their electroacoustic
      limitations.

PMID- 15238317
TI  - The long-term performance of electrically charged filters in a ventilation
      system.
AB  - The efficiency and pressure drop of filters made from polyolefin fibers carrying
      electrical charges were compared with efficiency and pressure drop for filters
      made from uncharged glass fibers to determine if the efficiency of the charged
      filters changed with use. Thirty glass fiber filters and 30 polyolefin fiber
      filters were placed in different, but nearly identical, air-handling units that
      supplied outside air to a large building. Using two kinds of real-time aerosol
      counting and sizing instruments, the efficiency of both sets of filters was
      measured repeatedly for more than 19 weeks while the air-handling units operated
      almost continuously. Pressure drop was recorded by the ventilation system's
      computer control. Measurements showed that the efficiency of the glass fiber
      filters remained almost constant with time. However, the charged polyolefin fiber
      filters exhibited large efficiency reductions with time before the efficiency
      began to increase again toward the end of the test. For particles 0.6 microm in
      diameter, the efficiency of the polyolefin fiber filters declined from 85% to 45%
      after 11 weeks before recovering to 65% at the end of the test. The pressure
      drops of the glass fiber filters increased by about 0.40 in. H2O, whereas the
      pressure drop of the polyolefin fiber filters increased by only 0.28 in. H2O. The
      results indicate that dust loading reduces the effectiveness of electrical
      charges on filter fibers.

PMID- 15238318
TI  - Estimating service lives of organic vapor cartridges II: a single vapor at all
      humidities.
AB  - A widely used equation model for estimating service lives of organic vapor air
      purifying respirator cartridges has been updated with more recent research
      results. It has been expanded to account for effects of high relative humidities.
      Adsorption capacity competition between water vapor and organic vapor is largely
      explained by mutual exclusion of adsorption volume of the activated carbon. The
      Dubinin/Radushkevich equation is used to describe the adsorption isotherms of
      both water and organic vapors. Effects of relative humidity and adsorbed water on
      adsorption rates are described by an empirical correlation with breakthrough
      times. The dynamic natures of adsorption and competition are incorporated using
      an expanding zone model with displaced water rollup. The complete model has been
      tested and verified with published and unpublished data from many sources.

PMID- 15238319
TI  - OSHA compliance issues: overexposure to dust in an animal feed ingredient
      manufacturing facility.

PMID- 15238320
TI  - Analytical performance criteria: an improved gold amalgam method for measurement
      of mercury vapor in the workplace.

PMID- 15238324
TI  - Effect of differing facial characteristics on breathing resistance inside a
      respirator mask.
AB  - A group of subjects with a large range of facial characteristics was asked to
      breathe deeply while wearing a full facepiece respirator. The facial
      characteristics noted were head length, head depth, bizygomatic breadth, lip
      length, and Menton-Sellion length. External resistances to inhalation or
      exhalation were varied in each of the trials. The data collected were analyzed
      for possible correlation between facial characteristics and breathing resistance.
      Although respirator resistances were found to vary, no statistically significant
      correlation was found with anthropometric measurements.

PMID- 15238321
TI  - Ergonomics: the impact of an intervention for lifting hazards during installation
      of overhead electrical conduit.

PMID- 15238325
TI  - Growth of mold on fiberglass insulation building materials--a review of the
      literature.
AB  - An exhaustive search of the literature on the growth of mold on fiberglass
      insulation materials was conducted. Because of the paucity of published material,
      both peer-reviewed and non-peer-reviewed articles were included. The literature
      indicates that fiberglass can serve as a support matrix for the collection of
      debris which, when moist, have the capability of supporting the growth of mold.
      Further, binding and paper-based moisture barriers from fiberglass resins are
      also capable of supporting the growth of mold when moist.

PMID- 15238326
TI  - Effectiveness of personal protective equipment: relevance of dermal and
      inhalation exposure to chlorpyrifos among pest control operators.
AB  - This study assessed the effectiveness of a custom fit personal protective
      equipment (PPE) program aimed at reducing occupational exposure to pesticides.
      The intervention study was carried out on 15 pest control operators (PCOs) during
      mixing/loading and application of chlorpyrifos. Each worker was measured twice;
      first while the worker used PPE as normal (baseline measurement), and second
      after making some adjustments to the PPE (postintervention measurement). The
      applied intervention consisted of a tight-fitting, full-face respirator, fit
      testing, long gloves, chemical-proof boots, a Tyvek hood, and an instruction
      video that was shown prior to putting on the PPE. A comprehensive evaluation
      program was used for the within-subject comparisons, including assessment of
      potential dermal exposure, actual dermal exposure, inhalation exposure, and
      internal dose as measured by the urinary metabolite 3,5,6-trichloro-2-pyridinol
      (TCP). The PPE program resulted in a significant increase in fit factors from a
      mean of 670 to 132,000. Actual dermal exposure levels decreased on average by
      fourfold after implementation of the PPE program (baseline AM = 132.1 microg;
      postintervention AM = 32.6 microg). The TCP levels in urine collected 24-32 hours
      after spray activities were lower in the postintervention data set (AM = 21.2
      microg TCP/g creatinine vs. AM = 13.9 microg TCP/g creatinine). However, it is
      impossible to attribute these differences totally to the PPE program since
      workers had significant and varying urinary TCP levels before onset of spraying
      activities. Linear regression models showed that dermal exposure was only a
      predictive parameter for TCP levels in urine in the baseline data set. Although
      the results should be interpreted cautiously this study suggests a protective
      effect of the evaluated PPE program.

PMID- 15238327
TI  - Evaluation of a sampling method for the measurement of occupational exposures to
      ethylene.
AB  - In an effort to assess the scope of occupational exposures to ethylene, the
      Olefins Panel of the American Chemistry Council designed and conducted a research
      project to develop and apply a sampling and analytical method to measure
      workplace exposure. The method uses packed Carbosieve S-III thermal desorption
      tubes (Supelco, Bellefonte, Pa.) with a low sample collection flow rate. The
      tubes were analyzed by thermal desorption gas chromatography. The methodology was
      validated for both 15-min short-term exposure limit and 8-hr time-weighted
      average (TWA) samples in the laboratory prior to the field study. The effects of
      varying sampling flow rate (2, 5, 10, and 25 mL/min) and temperature (25 and 35
      degrees C) on sample breakthrough time were assessed at a constant relative
      humidity of 90%. Breakthrough times decreased linearly with sampling flow rate
      and temperature. The optimal sampling flow rate and temperature at 90% relative
      humidity were 2 mL/ min and 25 degrees C. A full-shift TWA sample can be
      collected using two tubes for up to 4 hours each at a flow rate of 2 mL/min,
      while a STEL sample can be collected at 25 mL/min flow rate. The evaluation
      indicated samples can be stored under ambient conditions for a period up to 14
      days without significant sample loss. Field measurements were performed at 14
      petrochemical facilities within North America. The mean 8-hour TWA ethylene
      concentration (71 sample pairs) was 2.6 ppm (range: <0.05 to 2100 ppm).
      Significant ethylene concentrations were observed for only two of the 73 TWA
      sample pairs. Each of these two samples was obtained from the same facility, and
      only one tube of the sample pairs showed a high ethylene concentration (3200 ppm
      and 4200 ppm, respectively) for the 1600 ppm and 2100 ppm TWA sample. The first
      tube of each of these two sample pairs showed no detectable levels. Further, 69
      of 71 sample pairs had TWA concentrations below 13 ppm. The mean of 26 short-term
      exposure limit samples was 16 ppm (range: <0.05 to 63 ppm), with only one sample
      above 50 ppm. The results of this study indicate that airborne concentrations of
      ethylene can be effectively measured using Carbosieve S-III packed thermal
      desorption tubes under typical workplace conditions.

PMID- 15238328
TI  - Historical estimation of exposure to 1,3-butadiene, styrene, and
      dimethyldithiocarbamate among synthetic rubber workers.
AB  - Quantitative estimates of exposure to 1,3-butadiene (BD), styrene (STY), and
      dimethyldithiocarbamate (DMDTC) were developed for a follow-up study of workers
      at six North American synthetic rubber plants. Procedures entailed identifying
      tasks and jobs involving exposure, identifying factors influencing historical
      changes in exposure potential, and using mathematical models to calculate job-
      and time-period-specific exposures. Exposure metrics included 8-hour time
      weighted average (TWA) intensity, the annual number of peak exposures (BD: >100
      ppm, STY: >50 ppm) and TWA intensity below and above the peak threshold. The 5th
      and 95th percentiles of the approximate probability distribution of each exposure
      estimate served as its 90% uncertainty interval. Job- and year-specific estimates
      were linked with subjects' work histories to obtain cumulative exposure indices.
      Exposure estimates varied among tasks, jobs, plants, and time periods. BD TWAs
      were approximately 10 ppm during the 1940s-1960s and declined during the 1970s
      and 1980s. STY TWAs were always <2 ppm. DMDTC exposure began in the 1950s, was
      high through the 1960s, and later declined. BD peak exposure accounted for a
      large proportion of cumulative BD exposure, whereas almost none of the STY
      exposure was experienced at levels >50 ppm. Exposure indices were correlated.
      Exposures were higher than previously estimated. Multiple correlations among
      DMDTC, BD, and STY exposure estimates make it difficult to estimate agent
      specific effects. Limitations of the methodology include the potential inaccuracy
      of the estimates, the lack of adequate industrial hygiene data to validate the
      estimates, the additional inaccuracy of linkage with poorly specified job groups,
      and the potential for differential exposure misclassification because the jobs
      and work areas where excess leukemia mortality occurred were well-known at the
      time of this study. Nevertheless, the new exposure estimates were highly
      correlated with the old, yielding equivalent exposure ranking of workers and were
      comparable to limited industrial hygiene data published by NIOSH.

PMID- 15238329
TI  - Determination of the attenuation properties of laboratory gloves exposed to an
      ultraviolet transilluminator.
AB  - The transmission of ultraviolet radiation (UVR) from an ultraviolet
      transilluminator through three types of laboratory gloves (latex, nitrile, vinyl)
      was determined using two independent methods. First, transmittance was measured
      with a radiometer equipped with UVA and actinic UV detectors. Second, a
      spectrophotometer was used to determine the UVR transmittance vs. wavelength (250
      440 nm); this data was then used to compute the effective attenuation of the
      glove material. The average UVA percent transmittance using the radiometer method
      with an unstretched glove was 73.4%, 0.18%, and 1.10% for vinyl, nitrile, and
      latex, respectively. The average actinic percent transmittance for an unstretched
      glove was 13.3%, 0.015%, and 0.024% for vinyl, nitrile, and latex, respectively.
      Slight increases in UVR transmittance resulted from stretching the gloves by 30%
      or wetting them with saline. Six hours of UVR exposure decreased transmittance of
      vinyl gloves and increased transmittance by latex gloves. Results from the
      spectrophotometer method and radiometer methods of determining UVR transmittance
      agreed that vinyl gloves had the highest transmittance; however, the
      spectrophotometer method greatly overestimated UV glove attenuation due to the
      effect of light scattering by the glove material. The study suggests that in some
      circumstances, vinyl gloves will provide inadequate protection against workplace
      ultraviolet radiation.

PMID- 15238330
TI  - Occupational exposures during routine activities in coal-fueled power plants.
AB  - Limited information is available on occupational exposures during routine,
      nonoutage work activities in coal-fueled power plants. This study evaluated
      occupational exposures to the principal contaminants in the facilities, including
      respirable dust (coal dust), arsenic, noise, asbestos, and heat stress. The data
      were collected over a 3-month period, during the summer of 2001, in 5 facilities
      that were chosen to be representative of the coal-fueled power plants of a large
      southeastern power-generating company. Each of the facilities was divided into 5
      similar exposure groups based on previous exposure assessments and job tasks
      performed. From 4 of the 5 facilities, 392 air samples and 302 noise samples were
      collected with approximately 50 respirable coal dust, 32 arsenic, 15 asbestos,
      and 70 noise samples from each of the 4 plants. One of the previously surveyed
      facilities was also evaluated for heat stress, and 1 additional coal-fueled power
      plant was surveyed for a total of 20 personal heat stress samples. Personal
      monitors and area WBGT monitors were used. Of the nearly 400 air samples
      collected, only 1 exceeded the allowable occupational exposure value. For the
      noise samples, 55 (approximately 18%) were equal to or greater than the
      Occupational Safety and Health Administration (OSHA) 8-hour hearing conservation
      program level of 85 dBA, and 12 (approximately 4%) were equal to or greater than
      the OSHA 8-hour permissible exposure level of 90 dBA. Heat stress monitoring at
      the facilities indicates that 26% of the 1-hour TWAs were exceeded for one or all
      of the recommended heat stress limits. The data also concluded that some work
      sites were above the heat stress ceiling values recommended by the National
      Institute for Occupational Safety and Health (NIOSH). Four of the 20 employees
      personally monitored exceeded the recommended limits for heart rate or body core
      temperature. This suggests there is a potential for heat strain if signs and
      symptoms are ignored. Recommendations are made to better control the heat stress
      exposure.

PMID- 15238331
TI  - Comparison of ergonomist, supervisor, and worker assessments of work-related
      musculoskeletal risk factors.
AB  - In primary prevention efforts to reduce the incidence of work-related
      musculoskeletal disease (MSD), many employers will use supervisor or worker
      assessments for initial evaluation of MSD risk factors. This cross-sectional
      study examined the ability of supervisors and workers to accurately assess the
      presence of MSD risk factors at four work sites in four different industries,
      examining five jobs that represented six primary categories of risk factors:
      posture, force, repetition, impact, lifting, and vibration. Thirty-seven
      supervisors and 55 workers assessed the jobs they oversee or perform through the
      use of a 14-item questionnaire. Their assessments were compared with detailed
      ergonomist job analyses to determine their accuracy in identifying the presence
      or absence of MSD risk factors. In assessing the absence or presence of all risk
      factors, agreement with the ergonomist was found 81% of the time for supervisors
      and 77% of the time for workers. Overall, supervisors and workers overestimated
      the presence of risk in assessing the jobs. Supervisors and worker assessments
      appear promising in recognizing risk in initial ergonomic assessments.

PMID- 15238332
TI  - Construction welding exposures to manganese likely to exceed proposed TLV.

PMID- 15238333
TI  - Safety checklist for public schools--a useful tool for administrators and
      classroom teachers.

PMID- 15238335
TI  - The influence of exterior dust and soil lead on interior dust lead levels in
      housing that had undergone lead-based paint hazard control.
AB  - To aid in understanding the contribution of exterior dust/soil lead to
      postintervention interior dust lead, a subset of housing from the HUD Lead-Based
      Paint Hazard Control Grant Program Evaluation was selected for study. Housing
      from 12 state and local governments was included. Exterior entry and street dust
      samples were obtained by a vacuum method, and soil samples were building
      perimeter core composites. Interior dust wipe lead data (microg/ft(2)) and paint
      lead data (mg/cm(2)) were also available for each of the dwelling units and
      included in the modeling. Results from 541 dwelling units revealed a wide range
      of exterior dust and soil lead levels, within and between grantees. Minimum and
      maximum geometric mean lead levels, by grantee, were 126 and 14400 microg/ft(2)
      for exterior entry dust; 325 and 4610 microg/ft(2) for street dust; and, for soil
      concentration, 383 and 2640 ppm. Geometric mean exterior entry dust lead
      concentration (1641 ppm) was almost four times as high as street dust lead
      concentration (431 ppm), suggesting that lead dust near housing was often a
      source of street dust lead. Geometric mean exterior entry dust lead loading was
      more than four times as high as window trough dust lead loading and more than an
      order of magnitude higher than interior entry dust lead loading. Statistical
      modeling revealed pathways from exterior entry dust lead loading to loadings on
      interior entryway floors, other interior floors, and windowsills. Paint lead was
      found to influence exterior entry dust lead. Results of this study show that
      housing where soil lead hazard control activities had been performed had lower
      postintervention exterior entry, interior entry floor, windowsills, and other
      floor dust loading levels. Soil was not present for almost half the buildings.
      Statistical analysis revealed that exterior strategy influenced soil lead
      concentration, and soil lead concentration influenced street dust lead loading.
      This study represents one of the few where an impact of soil treatments on dust
      lead levels within the housing has been documented and may represent the first
      where an impact on exterior entry dust lead has been found. The inclusion of
      measures to mitigate the role of exterior sources in lead hazard control programs
      needs consideration.

PMID- 15238336
TI  - Effects of flange size on dividing streamlines of exterior hoods in cross drafts.
AB  - Effects of flange size on the flow patterns of an exterior circular hood subject
      to the influence of various uniform cross drafts were studied in an apparatus
      consisting of hood-model/wind-tunnel assembly. The cross draft to suction
      velocity ratio covered the range from 0.056 to 0.792. The flange width to hood
      diameter ratio spanned from 1.2 to 3.0. The hood equipped without flange was also
      probed. A two-component laser Doppler anemometer was used to measure the velocity
      field on the symmetry plane. The streamline patterns were obtained from the
      measured velocity data. The cross draft caused a capture envelope. The boundary
      of the envelope was described by a dividing streamline. It was found that the
      flange width presented complex effects on the capture envelope and the dividing
      streamline. Corresponding to a cross draft to suction velocity ratio, a critical
      flange width existed. If the flange width was smaller than the critical value,
      the dividing streamline would terminate at the downstream tip of the flange. The
      behaviors of the capture envelope and the dividing streamline of the hood in
      cross draft under different flange widths are presented and discussed.

PMID- 15238337
TI  - Effect of using a cowl when measuring the fiber number concentration by the
      membrane filter method.
AB  - This article compares samples taken with three different sampling heads: (1).
      open-faced sampling head, (2). open-faced sampling head with stainless-steel
      extension cowl, and (3). open-faced sampling head with graphite-impregnated
      extension cowl. Sampling was performed in three factories producing man-made
      mineral fibers (alkaline silicate fibers, refractory ceramic fibers, glass
      fibers). Flow rate was varied (1 L/min or 2 L/min). The average densities
      measured on the sampling filter for fibers of <3 microm in diameter varied from
      19 to 91 fibers/mm(2). No significant difference in fiber density was observed in
      relation to the nature of the sampling head for fibers with a diameter of <3
      microm. The deposits noted on the internal walls of the cowl were small and much
      less than that documented in the literature for man-made mineral fibers until
      now. They were greater for fibers with a diameter of >3 microm than for those
      with a diameter of <3 microm. For large-diameter fibers, it would appear that
      cowl deposit can be reduced by increasing the sampling flow rate.

PMID- 15238338
TI  - A screening-level assessment of the health risks of chronic smoke exposure for
      wildland firefighters.
AB  - A screening health risk assessment was performed to assess the upper-bound risks
      of cancer and noncancer adverse health effects among wildland firefighters
      performing wildfire suppression and prescribed burn management. Of the hundreds
      of chemicals in wildland fire smoke, we identified 15 substances of potential
      concern from the standpoints of concentration and toxicology; these included
      aldehydes, polycyclic aromatic hydrocarbons, carbon monoxide, benzene, and
      respirable particulate matter. Data defining daily exposures to smoke at
      prescribed burns and wildfires, potential days of exposure in a year, and career
      lengths were used to estimate average and reasonable maximum career inhalation
      exposures to these substances. Of the 15 substances in smoke that were evaluated,
      only benzene and formaldehyde posed a cancer risk greater than 1 per million,
      while only acrolein and respirable particulate matter exposures resulted in
      hazard indices greater than 1.0. The estimated upper-bound cancer risks ranged
      from 1.4 to 220 excess cancers per million, and noncancer hazard indices ranged
      from 9 to 360, depending on the exposure group. These values only indicate the
      likelihood of adverse health effects, not whether they will or will not occur.
      The risk assessment process narrows the field of substances that deserve further
      assessment, and the hazards identified by risk assessment generally agree with
      those identified as a concern in occupational exposure assessments.

PMID- 15238339
TI  - Current man-made mineral fibers (MMMF) exposures among ontario construction
      workers.
AB  - Current occupational exposures to man-made mineral fibers (MMMF), including
      refractory ceramic fibers (RCF), were measured as part of an exposure assessment
      program for an epidemiological study pertaining to cancer and mortality patterns
      of Ontario construction workers. The assessments were carried out at commercial
      and residential sites. A total of 130 MMMF samples (104 personal and 26 area) was
      collected and included 21 RCF (16 personal and 5 area). The samples were analyzed
      by the World Health Organization method in which both respirable and
      nonrespirable airborne fibers are counted. The results show that Ontario
      construction workers' full-shift exposure to MMMF (excluding RCF) is generally
      lower than the American Conference of Governmental Industrial Hygienists' (ACGIH)
      recommended threshold limit value-time-weighted average (TLV-TWA) of 1 fibers/cc
      and thus should not present any significant hazard. However, approximately 40% of
      the occupational exposures to RCF are higher than ACGIH's TLV-TWA of 0.2
      fibers/cc and present a significant potential hazard. Workers generally wore
      adequate approved respiratory protection, especially while performing
      particularly dusty tasks such as blowing, spraying, and cutting, so the actual
      exposure received by workers was lower than the reported values. Adequate control
      measures such as ventilation and respiratory protection should always be used
      when work involves RCF.

PMID- 15238340
TI  - A field evaluation of the predictive value of a hand-held drum pressure detection
      device.
AB  - According to Environmental Protection Agency estimates, 20% of hazardous waste
      drums currently managed in the 6500 known, uncontrolled Superfund removal or
      remediation sites contain some degree of elevated internal pressurization. This
      estimate increases to 90% during the summer months, and, overall, up to 5% of the
      drums stored in active treatment, storage, and disposal facilities may be
      pressurized. The ability to identify pressurized drums in real-time would enhance
      worker health and safety, reduce the potential for environmental contamination,
      and minimize property damage. A prototype hand-held drum pressure detection
      device was field tested at an active Resource Conservation and Recovery Act mixed
      waste operation using acoustic resonance spectroscopy technology to identify
      pressurized drums. The waste operation used a drum venting system that measured
      the actual drum pressure of retrieved drums. Drum venting system data were
      analyzed to quantify the ability of the drum pressure detection device to
      correctly identify drums with elevated internal pressure. After 456 drums were
      measured, the dichotomous pressure data (pressurized vs. nonpressurized) were
      analyzed. The relationship between the drum venting system and drum pressure
      detection device pressure data was found to be statistically significant. With
      alpha and beta values of 0.05, the negative predictive value was 0.94, the
      positive predictive value was 0.47, the sensitivity was 0.82, and the specificity
      was 0.77. Although capable of identifying nonpressurized drums, this instrument
      may not be appropriate for general use. Study results and critical improvements
      necessary to improve the instrument's predictive value, specificity, and
      sensitivity are presented.

PMID- 15238341
TI  - Urinary cadmium levels in the U S working population, 1988-1994.
AB  - Few studies have estimated the prevalence and mean urinary cadmium levels in U.S.
      workers and the factors associated with high cadmium exposure. In this study,
      urinary cadmium measurements were obtained on 11228 U.S. workers aged 18 to 64
      years who participated in the Third National Health and Nutrition Examination
      Survey (NHANES III, 1988-1994). Urinary cadmium levels ranged from 0.01 to 15.57
      microg/L, with a geometric mean of 0.30 microg/L (0.28 microg/g creatinine) for
      all U.S. workers. The prevalence of urinary cadmium levels >or=5 microg/L was
      0.42% (551000) for U.S. workers aged 18 to 64 years. Among U.S. workers in the
      metal industry (two-digit Standard Industrial Classification or SIC codes 33 and
      34), the geometric mean urinary cadmium level was 0.48 microg/L (0.39 microg/g
      creatinine), and 0.45% of these workers had urinary cadmium levels >or=10
      microg/L. The prevalence of urinary cadmium levels >or=15 microg/L was 0.0028%
      (3907). The agriculture industry (two-digit SIC codes 01, 02, and 07-09) was
      associated with low urinary cadmium levels, compared with repair services
      industries (two-digit SIC codes 75 and 76). Results from ordinary least squares
      regression analyses indicated that smokers had significantly higher urinary
      cadmium levels than nonsmokers (p <or= 0.0001). The results also showed that
      there were high urinary cadmium levels among workers in selected occupations and
      industries.

PMID- 15238342
TI  - Laboratory evaluation of a potential diesel fuel interference in the
      determination of polycyclic aromatic compounds on dermal samplers.
AB  - Road pavers are exposed to asphalt fumes through dermal contact, inhalation, or
      ingestion. These fumes contain polycyclic aromatic compounds (PACs), a class of
      compounds including polycyclic aromatic hydrocarbons (PAHs). The PAHs include
      compounds such as pyrene and benzo(a)pyrene and a large number of other compounds
      of known or suspected carcinogenicity. To estimate dermal deposition of asphalt
      fume particulate matter, polypropylene sampling patches can be worn on a worker's
      inside wrist. Diesel fuel used for cleaning can splash onto the dermal sampler.
      Exposed dermal patches were solvent extracted and PACs estimated in the extract
      using a modification of NIOSH Method 5800. The final solution was analyzed by
      high pressure liquid chromatography (HPLC) with a fluorescence detector using an
      excitation wavelength of 270 nanometers and an emission wavelength of 415
      nanometers. The PACs were concentrated on a C-18 reverse phase guard column but
      not separated so that they could be measured expediently as a group. In this
      study we examined whether deposited diesel fuel interferes with the HPLC
      determination of PACs. We characterized the effect of diesel fuel contamination
      over broad ranges of both analyte and interferent. Two drops, or approximately
      100 microL, of diesel fuel on the dermal samplers caused an overestimation of the
      concentration of polycyclic aromatic compounds (PACs). In the range of PACs
      determined in our field study (0 to 54 microg per sample), these errors could
      have exceeded 100%. Because 100 microL of deposited diesel fuel produced a clear
      visual "wetness," this observation can serve as one of the criteria for sample
      rejection. Sampling media must be examined carefully for visible contamination to
      prevent bias in the measurement of PACs deposited from asphalt fume.

PMID- 15238343
TI  - An industrial hygiene survey of an office building in the vicinity of the World
      Trade Center: assessment of potential hazards following the collapse of the world
      trade center buildings.

PMID- 15238344
TI  - Exposure to carbon monoxide from material handling equipment.

PMID- 15238345
TI  - A summary of the workshop applying biomarkers to occupational health practice.

PMID- 15238348
TI  - Changes in leaf trichomes and epicuticular flavonoids during leaf development in
      three birch taxa.
AB  - BACKGROUND AND AIMS: Changes in number of trichomes and in composition and
      concentrations of their exudates throughout leaf development may have important
      consequences for plant adaptation to abiotic and biotic factors. In the present
      study, seasonal changes in leaf trichomes and epicuticular flavonoid aglycones in
      three Finnish birch taxa (Betula pendula, B. pubescens ssp. pubescens, and B.
      pubescens ssp. czerepanovii) were followed. METHODS: Trichome number and
      ultrastructure were studied by means of light, scanning and transmission electron
      microscopy, while flavonoid aglycones in ethanolic leaf surface extracts were
      analysed by high-pressure liquid chromatography. KEY RESULTS: Density of both
      glandular and non-glandular trichomes decreased drastically with leaf expansion
      while the total number of trichomes per leaf remained constant, indicating that
      the final number of trichomes is established early in leaf development. Cells of
      glandular trichomes differentiate before those of the epidermis and produce
      secreted material only during the relatively short period (around 1-2 weeks) of
      leaf unfolding and expansion. In fully expanded leaves, glandular trichomes
      appeared to be at the post-secretory phase and function mainly as storage organs;
      they contained lipid droplets and osmiophilic material (probably phenolics).
      Concentrations (mg g(-1) d. wt) of surface flavonoids decreased with leaf age in
      all taxa. However, the changes in total amount ( microg per leaf) of flavonoids
      during leaf development were taxon-specific: no changes in B. pubescens ssp.
      czerepanovii, increase in B. pendula and in B. pubescens ssp. pubescens followed
      by the decline in the latter taxon. Concentrations of most of the individual leaf
      surface flavonoids correlated positively with the density of glandular trichomes
      within species, suggesting the participation of glandular trichomes in production
      of surface flavonoids. CONCLUSIONS: Rapid decline in the density of leaf
      trichomes and in the concentrations of flavonoid aglycones with leaf age suggests
      that the functional role of trichomes is likely to be most important at the early
      stages of birch leaf development.

PMID- 15238349
TI  - Acid phosphatase role in chickpea/maize intercropping.
AB  - BACKGROUND AND AIMS: Organic P comprises 30-80 % of the total P in most
      agricultural soils. It has been proven that chickpea facilitates P uptake from an
      organic P source by intercropped wheat. In this study, acid phosphatase excreted
      from chickpea roots is quantified and the contribution of acid phosphatase to the
      facilitation of P uptake by intercropped maize receiving phytate is examined.
      METHODS: For the first experiment using hydroponics, maize (Zea mays 'Zhongdan
      No. 2') and chickpea (Cicer arietinum 'Sona') were grown in either the same or
      separate containers, and P was supplied as phytate, KH2PO4 at 0.25 mmol P L(-1),
      or not at all. The second experiment involved soil culture with three types of
      root separation between the two species: (1) plastic sheet, (2) nylon mesh, and
      (3) no barrier. Maize plants were grown in one compartment and chickpea in the
      other. Phosphorus was supplied as phytate, Ca(H2PO4)2 at 50 mg P kg(-1), or no P
      added. KEY RESULTS: In the hydroponics study, the total P uptake by intercropped
      maize supplied with phytate was 2.1-fold greater than when it was grown as a
      monoculture. In the soil experiment, when supplied with phytate, total P uptake
      by maize with mesh barrier and without root barrier was 2.2 and 1.5 times,
      respectively, as much as that with solid barrier. In both experiments, roots of
      both maize and chickpea supplied with phytate and no P secreted more acid
      phosphatase than those with KH2PO4 or Ca(H2PO4)2. However, average acid
      phosphatase activity of chickpea roots supplied with phytate was 2-3-fold as much
      as maize. Soil acid phosphatase activity in the rhizosphere of chickpea was also
      significantly higher than maize regardless of P sources. CONCLUSIONS: Chickpea
      can mobilize organic P in both hydroponic and soil cultures, leading to an
      interspecific facilitation in utilization of organic P in maize/chickpea
      intercropping.

PMID- 15238350
TI  - Effects of self-, chase and mixed self/cross-pollinations on pistil longevity and
      fruit set in Ceiba species (Bombacaceae) with late-acting self-incompatibility.
AB  - BACKGROUND AND AIMS: Late-acting self-incompatibility (LSI), in which selfed
      flowers fail to form fruits despite apparently successful growth of the pollen
      tubes to the ovules, is a contentious and still poorly understood phenomenon.
      Some studies have indicated pollen tube-pistil interactions, and major gene
      control. Others favour an early acting inbreeding depression explanation.
      METHODS: Experimental pollinations, including selfs (in a subsample of which the
      style was cut before pollen tubes reached the ovary), chase self/cross
      pollinations, crosses, and mixed self/cross-pollinations were used to study
      floral/pistil longevity and effect on fruit set and seed yield in two Ceiba
      species known to have LSI. RESULTS: Self-pollinations, including those with a cut
      style, had extended floral longevity compared with unpollinated flowers. Chase
      pollinations in which cross-pollen was applied up to 3 h after selfing set
      fruits, but with reduced seed set compared with crosses. Those with cross-pollen
      applied at 4 and 8 h after self-pollination all failed to set fruits. Flowers
      subjected to 1 : 1 and 2 : 1 self/cross-pollinations all produced fruits but
      again with a significantly lower seed set compared with crosses. CONCLUSIONS:
      Extended floral longevity initiated with self-pollen tubes growing in the style
      indicates some kind of pollen tube-pistil interaction. Fruit set only in chase
      pollinations up to 3 h implies that self-pollen tubes either grow more slowly in
      the style or penetrate ovules more slowly on arrival at the ovary compared with
      cross-tubes. This agrees with previous observations indicating that the incidence
      of penetrated ovules is initially lower in selfed compared with crossed pistils.
      However, the low seed yield from mixed pollinations indicates that self- and
      cross-pollen tubes arrive at the ovary and penetrate ovules more or less
      simultaneously. Possible explanations for these discordant results are discussed.

PMID- 15238351
TI  - Recovery of Na-glucose cotransport activity after renal ischemia is impaired in
      mice lacking vimentin.
AB  - Vimentin, an intermediate filament protein mainly expressed in mesenchyma-derived
      cells, is reexpressed in renal tubular epithelial cells under many pathological
      conditions, characterized by intense cell proliferation. Whether vimentin
      reexpression is only a marker of cell dedifferentiation or is instrumental in the
      maintenance of cell structure and/or function is still unknown. Here, we used
      vimentin knockout mice (Vim(-/-)) and an experimental model of acute renal injury
      (30-min bilateral renal ischemia) to explore the role of vimentin. Bilateral
      renal ischemia induced an initial phase of acute tubular necrosis that did not
      require vimentin and was similar, in terms of morphological and functional
      changes, in Vim(+/+) and Vim(-/-) mice. However, vimentin was essential to favor
      Na-glucose cotransporter 1 localization to brush-border membranes and to restore
      Na-glucose cotransport activity in regenerating tubular cells. We show that the
      effect of vimentin inactivation is specific and results in persistent glucosuria.
      We propose that vimentin is part of a structural network that favors carrier
      localization to plasma membranes to restore transport activity in injured
      kidneys.

PMID- 15238352
TI  - Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit
      renal proximal tubules.
AB  - We investigated the regulation of organic anion transport driven by the organic
      anion transporter 3 (OAT3), a multispecific OAT localized at the basolateral
      membrane of the renal proximal tubule. PMA, a PKC activator, inhibited uptake of
      estrone sulfate (ES), a prototypic substrate for OAT3, in a dose- and time
      dependent manner. This inhibition was reduced by 100 nM bisindoylmaleimide I
      (BIM), a specific PKC inhibitor. The alpha(1)-adrenergic receptor agonist
      phenylephrine also inhibited ES uptake, and this effect was reduced by BIM. These
      results suggest that PKC activation downregulates OAT3-mediated organic anion
      transport. In contrast, epidermal growth factor (EGF) increased ES uptake
      following activation of MAPK. Exposure to PGE(2) or dibutyryl (db)-cAMP also
      enhanced ES uptake. Stimulation produced by PGE(2) and db-cAMP was prevented by
      the PKA inhibitor H-89, indicating that this stimulation required PKA activation.
      In addition, inhibition of cyclooxygenase 1 (COX1) (but not COX2) inhibited ES
      uptake. Furthermore, the stimulatory effect of EGF was eliminated by inhibition
      of either COX1 or PKA. These data suggest that EGF stimulates ES uptake by a
      process in which MAPK activation results in increased PGE(2) production that, in
      turn, activates PKA and subsequently stimulates ES uptake. Interestingly, EGF did
      not induce upregulation immediately following phenylephrine-induced
      downregulation; and phenylephrine did not induce downregulation immediately after
      EGF-induced upregulation. These data are the first to show the regulatory
      response of organic anion transport driven by OAT3 in intact renal proximal
      tubules.

PMID- 15238353
TI  - Glucocorticoid exposure in late gestation in the rat permanently programs gender
      specific differences in adult cardiovascular and metabolic physiology.
AB  - Glucocorticoid overexposure in utero may underlie the association between low
      birth weight and subsequent development of common cardiovascular and metabolic
      pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure
      in rat reduces birth weight and programs the hypothalamic-pituitary axis and
      fasting and postprandial hyperglycemia in adult males and hypertension in adult
      males and females. This study aimed to determine 1) whether there were gender
      differences in prenatal DEX-programmed offspring, and 2) whether the renin
      angiotensin system (RAS) plays a role in the programming of hypertension. Rats
      exposed to DEX in utero (100 microg.kg(-1).day(-1) from embryonic days 14-21)
      were of lower birth weight (by 12%, P < 0.01) and displayed full catch-up growth
      within the first month of postnatal life. DEX-treated male offspring in adulthood
      selectively displayed elevated plasma adrenocorticotropic hormone (by 221%) and
      corticosterone (by 188%, P < 0.05), postprandial insulin-glucose ratios (by 100%,
      P < 0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate
      carboxykinase (by 38%, P < 0.05). Conversely, DEX-programmed females were
      hypertensive (by 11%, P < 0.05), with elevated hepatic angiotensinogen mRNA
      expression (by 9%, P < 0.05), plasma angiotensinogen (by 61%, P < 0.05), and
      renin activity (by 88%, P < 0.05). These findings demonstrate that prenatal
      glucocorticoids program adulthood cardiovascular and metabolic physiology in a
      gender-specific pattern, and that an activated RAS may in part underlie the
      hypertension associated with prenatal DEX programming.

PMID- 15238354
TI  - Dual-energy X-ray absorptiometry lean soft tissue hydration: independent
      contributions of intra- and extracellular water.
AB  - Dual-energy X-ray absorptiometry (DEXA) provides a measure of lean soft tissue
      (LST). LST hydration, often assumed to be constant, is relevant to several
      aspects of DEXA body composition estimates. The aims of this study were to
      develop a theoretical model of LST total body water (TBW) content and to examine
      hydration effects with empirically derived model coefficients and then to
      experimentally test the model's prediction that, in healthy adults, LST hydration
      is not constant but varies as a function of extra- and intracellular water
      distribution (E/I). The initial phase involved TBW/LST model development and
      application with empirically derived model coefficients. Model predictions were
      then tested in a cross-sectional study of 215 healthy adults. LST was measured by
      DEXA, extracellular water (ECW) by NaBr dilution, intracellular water (ICW) by
      whole body (40)K counting, and TBW by (2)H(2)O dilution. TBW estimates,
      calculated as ECW + ICW, were highly correlated with (r = 0.97, SEE = 2.1 kg, P <
      0.001) and showed no significant bias compared with TBW measured by (2)H(2)O.
      Model-predicted TBW/LST was almost identical to experimentally derived values
      (means +/- SD) in the total group (0.767 vs. 0.764 +/- 0.028). LST hydration was
      significantly correlated with E/I (total group, r = 0.30, SEE = 0.027, P <
      0.001). Although E/I increased with age (men, r = 0.48; women, r = 0.37; both P <
      0.001), the association between TBW/LST and age was nonsignificant. Hydration of
      the DEXA-derived LST compartment is thus not constant but varies predictably with
      ECW and ICW distribution. This observation has implications for the accuracy of
      body fat measurements by DEXA and the use of TBW as a means of checking DEXA
      system calibration.

PMID- 15238356
TI  - Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen
      species can act as second messengers.
AB  - Except for the role of NO in the activation of guanylate cyclase, which is well
      established, the involvement of reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) in signal transduction remains controversial, despite a
      large body of evidence suggestive of their participation in a variety of
      signaling pathways. Several problems have limited their acceptance as signaling
      molecules, with the major one being the difficulty in identifying the specific
      targets for each pathway and the chemical reactions supporting reversible
      oxidation of these signaling components, consistent with a second messenger role
      for ROS and RNS. Nevertheless, it has become clear that cysteine residues in the
      thiolate (i.e., ionized) form that are found in some proteins can be specific
      targets for reaction with H(2)O(2) and RNS. This review focuses on the chemistry
      of the reversible oxidation of those thiolates, with a particular emphasis on the
      critical thiolate found in protein tyrosine phosphatases as an example.

PMID- 15238357
TI  - Fluorescence imaging in living animals. Focus on "Uptake and trafficking of
      fluorescent conjugates of folic acid in intact kidney determined using intravital
      two-photon microscopy".

PMID- 15238358
TI  - Extracellular ATP: a central player in the regulation of vascular smooth muscle
      phenotype. Focus on "Dual role of PKA in phenotype modulation of vascular smooth
      muscle cells by extracellular ATP".

PMID- 15238359
TI  - L-Carnitine transport in human placental brush-border membranes is mediated by
      the sodium-dependent organic cation transporter OCTN2.
AB  - Maternofetal transport of l-carnitine, a molecule that shuttles long-chain fatty
      acids to the mitochondria for oxidation, is thought to be important in preparing
      the fetus for its lipid-rich postnatal milk diet. Using brush-border membrane
      (BBM) vesicles from human term placentas, we showed that l-carnitine uptake was
      sodium and temperature dependent, showed high affinity for carnitine (apparent
      K(m) = 11.09 +/- 1.32 microM; V(max) = 41.75 +/- 0.94 pmol.mg protein(-1).min(
      1)), and was unchanged over the pH range from 5.5 to 8.5. l-Carnitine uptake was
      inhibited in BBM vesicles by valproate, verapamil, tetraethylammonium, and
      pyrilamine and by structural analogs of l-carnitine, including d-carnitine,
      acetyl-d,l-carnitine, and propionyl-, butyryl-, octanoyl-, isovaleryl-, and
      palmitoyl-l-carnitine. Western blot analysis revealed that OCTN2, a high
      affinity, Na(+)-dependent carnitine transporter, was present in placental BBM but
      not in isolated basal plasma membrane vesicles. The reported properties of OCTN2
      resemble those observed for l-carnitine uptake in placental BBM vesicles,
      suggesting that OCTN2 may mediate most maternofetal carnitine transport in
      humans.

PMID- 15238360
TI  - Dual role of PKA in phenotypic modulation of vascular smooth muscle cells by
      extracellular ATP.
AB  - Extracellular ATP is released from activated platelets and endothelial cells and
      stimulates proliferation of vascular smooth muscle cells (VSMC). We found that
      ATP stimulates a profound but transient activation of protein kinase A (PKA) via
      purinergic P2Y receptors. The specific inhibition of PKA by adenovirus-mediated
      transduction of the PKA inhibitor (PKI) attenuates VSMC proliferation in response
      to ATP, suggesting a positive role for transient PKA activation in VSMC
      proliferation. By contrast, isoproterenol and forskolin, which stimulate a more
      sustained PKA activation, inhibit VSMC growth as expected. On the other hand, the
      activity of serum response factor (SRF) and the SRF-dependent expression of
      smooth muscle (SM) genes, such as SM-alpha-actin and SM22, are extremely
      sensitive to regulation by PKA, and even transient PKA activation by ATP is
      sufficient for their downregulation. Analysis of the dose responses of PKA
      activation, VSMC proliferation, SRF activity, and SM gene expression to ATP, with
      or without PKI overexpression, suggests the following model for the phenotypic
      modulation of VSMC by ATP, in which the transient PKA activation plays a critical
      role. At low micromolar doses, ATP elicits a negligible effect on DNA synthesis
      but induces profound SRF activity and SM gene expression, thus promoting the
      contractile VSMC phenotype. At high micromolar doses, ATP inhibits SRF activity
      and SM gene expression and promotes VSMC growth in a manner dependent on
      transient PKA activation. Transformation of VSMC by high doses of ATP can be
      prevented and even reversed by inhibition of PKA activity.

PMID- 15238361
TI  - Calcitonin gene-related peptide elevates calcium and polarizes membrane potential
      in MG-63 cells by both cAMP-independent and -dependent mechanisms.
AB  - Published data suggest that the neuropeptide calcitonin gene-related peptide
      (CGRP) can stimulate osteoblastic bone formation; however, interest has focused
      on activation of cAMP-dependent signaling pathways in osteogenic cells without
      full consideration of the importance of cAMP-independent signaling. We have now
      examined the effects of CGRP on intracellular Ca(2+) concentration
      ([Ca(2+)](int)) and membrane potential (E(m)) in preosteoblastic human MG-63
      cells by single-cell fluorescent confocal analysis using fluo 4-AM-fura red-AM
      and bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)] bis-oxonol assays.
      CGRP produced a two-stage change in [Ca(2+)](int): a rapid transient peak and a
      secondary sustained increase. Both responses were dose dependent with an EC(50)
      of approximately 0.30 nM, and the maximal effect (initially approximately 3-fold
      over basal levels) was observed at 20 nM. The initial phase was sensitive to
      inhibition of Ca(2+) mobilization with thapsigargin, whereas the secondary phase
      was eliminated only by blocking transmembrane Ca(2+) influx with verapamil or
      inhibiting cAMP-dependent signaling with the Rp isomer of adenosine 3',5'-cyclic
      monophosphorothioate (Rp-cAMPS). These data suggest that CGRP initially
      stimulates Ca(2+) discharge from intracellular stores by a cAMP-independent
      mechanism and subsequently stimulates Ca(2+) influx through L-type voltage
      dependent Ca(2+) channels by a cAMP-dependent mechanism. In addition, CGRP dose
      dependently polarized cellular E(m), with maximal effect at 20 nM and an EC(50)
      of 0.30 nM. This effect was attenuated with charybdotoxin (-20%) or glyburide
      (glibenclamide; -80%), suggesting that E(m) hyperpolarization is induced by both
      Ca(2+)-activated and ATP-sensitive K(+) channels. Thus CGRP signals strongly by
      both cAMP-dependent and cAMP-independent signaling pathways in preosteoblastic
      human MG-63 cells.

PMID- 15238362
TI  - LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells:
      stimulation of retinoic acid production and protection from ethanol toxicity.
AB  - Retinoic acid (RA) is required for the normal growth and maintenance of many cell
      types, including lens epithelial cells (LECs). Alcohol (ADH) and aldehyde (ALDH)
      dehydrogenases are implicated in cellular detoxification and conversion of
      vitamin A to RA. Lens epithelium-derived growth factor (LEDGF) provides cellular
      protection against stress by transactivating stress-associated genes. Here we
      show evidence that LEDGF binds and transactivates heat shock (nGAAn) and stress
      response (A/TGGGGA/T) elements in the promoters of ADH1, ADH4, and retinaldehyde
      2 (RALDH2) genes. Electrophoretic mobility and supershift assays disclosed
      specific binding of LEDGF to nGAAn and A/TGGGGA/T elements in these gene
      promoters. Transfection experiments in LECs with promoters linked to a
      chloramphenicol acetyltransferase (CAT) reporter gene along with LEDGF cDNA
      revealed higher CAT activity. RT-PCR results confirmed that LECs overexpressing
      LEDGF contained increased levels of ADH1, ADH4, and RALDH2 mRNA. Notably, LECs
      displayed higher LEDGF mRNA and protein expression during ethanol stress. Cells
      overexpressing LEDGF typically exhibited elevated RA levels and survived well
      during ethanol stress. The present findings indicate that LEDGF is one of the
      transcriptional activators of these genes that facilitates cellular protection
      against ethanol stress and plays a role in RA production.

PMID- 15238363
TI  - Comparative analysis of protein unfoldedness in human housekeeping and non
      housekeeping proteins.
AB  - Absence of any regular structure is increasingly being observed in structural
      studies of proteins. These disordered regions or random coils, which have been
      observed under physiological conditions, are indicators of protein plasticity.
      The wide variety of interactions possible due to the flexibility of these
      'natively disordered' regions confers functional advantage to the protein and the
      organism in general. This concept is underscored by the increasing proportion of
      intrinsically unstructured proteins seen with the ascension in the complexity of
      the organisms. The 'natively unfolded/disordered' state of the protein can be
      predicted utilizing Uversky's or Dunker's algorithm. We utilized Uversky's
      prediction scheme and based on the unique position of a protein in the charge
      hydrophobicity plot, a derived net score was used to predict the overall disorder
      of the human housekeeping and non-housekeeping proteins. Substantial numbers of
      proteins in both the classes were predicted to be unfolded. However, comparative
      genomic analysis of predicted unfolded Homo sapiens proteins with homologues in
      Caenorhabditis elegans, Drosophila melanogaster and Mus musculus revealed
      significant increase in unfoldedness in non-housekeeping proteins in comparison
      with housekeeping proteins. Our analysis in the evolutionary context suggests
      addition or substitution of amino acid residues which favour unfoldedness in non
      housekeeping proteins compared to housekeeping proteins.

PMID- 15238364
TI  - Hand hygiene among physicians: performance, beliefs, and perceptions.
AB  - BACKGROUND: Physician adherence to hand hygiene remains low in most hospitals.
      OBJECTIVES: To identify risk factors for nonadherence and assess beliefs and
      perceptions associated with hand hygiene among physicians. DESIGN: Cross
      sectional survey of physician practices, beliefs, and attitudes toward hand
      hygiene. SETTING: Large university hospital. PARTICIPANTS: 163 physicians.
      MEASUREMENTS: Individual observation of physician hand hygiene practices during
      routine patient care with documentation of relevant risk factors; self-report
      questionnaire to measure beliefs and perceptions. Logistic regression identified
      variables independently associated with adherence. RESULTS: Adherence averaged
      57% and varied markedly across medical specialties. In multivariate analysis,
      adherence was associated with the awareness of being observed, the belief of
      being a role model for other colleagues, a positive attitude toward hand hygiene
      after patient contact, and easy access to hand-rub solution. Conversely, high
      workload, activities associated with a high risk for cross-transmission, and
      certain technical medical specialties (surgery, anesthesiology, emergency
      medicine, and intensive care medicine) were risk factors for nonadherence.
      LIMITATIONS: Direct observation of physicians may have influenced both adherence
      to hand hygiene and responses to the self-report questionnaire. Generalizability
      of study results requires additional testing in other health care settings and
      physician populations. CONCLUSION: Physician adherence to hand hygiene is
      associated with work and system constraints, as well as knowledge and cognitive
      factors. At the individual level, strengthening a positive attitude toward hand
      hygiene and reinforcing the conviction that each individual can influence the
      group behavior may improve adherence among physicians. Physicians who work in
      technical specialties should also be targeted for improvement.

PMID- 15238365
TI  - Plasma level of a triggering receptor expressed on myeloid cells-1: its
      diagnostic accuracy in patients with suspected sepsis.
AB  - BACKGROUND: Previous experimental studies have suggested that the triggering
      receptor expressed on myeloid cells-1 (TREM-1) is specifically upregulated in the
      presence of microbial products. OBJECTIVE: To evaluate the diagnostic value of
      plasma levels of the soluble form of TREM-1 in patients admitted with clinical
      suspicion of infection. DESIGN: Prospective, noninterventional study conducted
      between July and September 2003. SETTING: Medical adult intensive care unit at a
      university hospital in France. PARTICIPANTS: 76 consecutive newly admitted
      patients who presented with clinically suspected infection and fulfilled at least
      2 criteria of the systemic inflammatory response syndrome. MEASUREMENTS:
      Sensitivity and specificity of plasma soluble TREM-1 levels at admission for the
      diagnosis of infection. Two independent intensivists blinded to the results of
      soluble TREM-1 assays retrospectively classified patients as having the systemic
      inflammatory response syndrome, sepsis, severe sepsis, or septic shock. RESULTS:
      The systemic inflammatory response syndrome was diagnosed in 29 patients (38%),
      and sepsis, severe sepsis, or septic shock was diagnosed in the remaining 47
      (62%). A plasma soluble TREM-1 level higher than 60 ng/mL was more accurate than
      any other clinical or laboratory finding for indicating infection (sensitivity,
      96% [95% CI, 92% to 100%]; specificity, 89% [CI, 82% to 95%]; positive likelihood
      ratio, 8.6 [CI, 3.8 to 21.5]; negative likelihood ratio, 0.04 [CI, 0.01 to 0.2]).
      LIMITATIONS: The study did not enroll patients with mild infections not requiring
      intensive care unit hospitalization, patients older than 80 years of age, or
      patients who were immunocompromised. CONCLUSION: In newly admitted critically ill
      patients, measurement of plasma levels of soluble TREM-1 could help to rapidly
      identify those with infection.

PMID- 15238366
TI  - Cross-reactivity and tolerability of cephalosporins in patients with immediate
      hypersensitivity to penicillins.
AB  - BACKGROUND: In patients with documented IgE-mediated hypersensitivity to
      penicillins, data on sensitization to cephalosporins vary. Administering
      cephalosporins to such patients is often deferred because of the risk for cross
      reactivity. OBJECTIVE: To assess the cross-reactivity with cephalosporins and its
      potential determinants in patients with documented penicillin allergy. DESIGN:
      Prospective study in patients without clinical indications for cephalosporin
      treatment. SETTING: Italy. PATIENTS: 128 consecutive patients who sustained
      anaphylactic shock (n = 81) or urticaria (n = 47) and had positive results on
      skin tests for at least 1 of the penicillin reagents tested. MEASUREMENTS: All
      patients were skin tested with cephalothin, cefamandole, cefuroxime, ceftazidime,
      ceftriaxone, and cefotaxime. Patients with negative results for the last 4
      cephalosporins were challenged with cefuroxime axetil and ceftriaxone. RESULTS:
      14 patients (10.9% [95% CI, 6.1% to 17.7%]) had positive results on skin tests
      for cephalosporins, mostly for cephalothin or cefamandole. Skin test results for
      the minor determinant mixture were positive in 10 of 14 patients (71.4%) with
      cross-reactivity and 44 of 114 patients (38.6%) without cross-reactivity (odds
      ratio, 3.90 [CI, 1.17 to 13.40]; P = 0.0189). All 101 patients with negative
      results on skin tests for cefuroxime, ceftazidime, ceftriaxone, and cefotaxime
      tolerated cefuroxime axetil and ceftriaxone (tolerability rate, 100% [CI, 96.4%
      to 100%]). LIMITATIONS: Challenges were not followed by full therapeutic courses.
      Twenty-two patients declined challenges; positive responses in those patients
      would have decreased the tolerability rate to 82.1% (CI, 74.2% to 88.4%).
      CONCLUSIONS: These data confirm the advisability of avoiding cephalosporin
      treatment in patients with positive results on skin tests for penicillin. In
      patients who especially require cephalosporin treatment, we recommend skin tests
      with cephalosporins before assessing the tolerability of the cephalosporin with a
      graded challenge.

PMID- 15238367
TI  - Brief communication: American ginseng reduces warfarin's effect in healthy
      patients: a randomized, controlled Trial.
AB  - BACKGROUND: People using prescription medication often concurrently take herbal
      supplements. In a case report, the anticoagulant effect of warfarin decreased
      after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between
      American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo
      controlled trial. SETTING: General Clinical Research Center, University of
      Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In
      this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4.
      Beginning in week 2, patients were assigned to receive either American ginseng or
      placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin
      level. RESULTS: The peak INR statistically significantly decreased after 2 weeks
      of ginseng administration compared with placebo (difference between ginseng and
      placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the
      curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically
      significantly reduced in the ginseng group as compared with the placebo group.
      Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS:
      The study sample consisted of young, healthy volunteers in a research setting
      rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American
      ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin,
      physicians should ask patients about ginseng use.

PMID- 15238368
TI  - Medical and surgical comanagement after elective hip and knee arthroplasty: a
      randomized, controlled trial.
AB  - BACKGROUND: Hospitalists are assuming an increasing role in the care of surgical
      patients, but the impact of this model of care on postoperative outcomes is
      unknown. OBJECTIVE: To determine the impact of providing a collaborative,
      hospitalist-led model of care on postoperative outcomes and costs among patients
      having hip or knee arthroplasty. DESIGN: Randomized, controlled trial. SETTING:
      Academic medical center. PARTICIPANTS: 526 patients having elective orthopedic
      surgery who are at elevated risk for postoperative morbidity. MEASUREMENTS:
      Length of stay, inpatient postoperative medical complications, health care
      provider satisfaction, and inpatient costs. INTERVENTIONS: A comanagement medical
      Hospitalist-Orthopedic Team compared with standard postoperative care by
      orthopedic surgeons with medical consultation. RESULTS: More patients in the
      hospitalist group were discharged from the hospital with no complications (61.6%
      vs. 49.8%; difference, 11.8 percentage points [95% CI, 2.8 to 20.7 percentage
      points]). Fewer minor complications were observed among hospitalist patients
      (30.2% vs. 44.3%; difference, -14.1 percentage points [CI, -22.7 to -5.3
      percentage points]). Observed length of stay was not statistically different
      between treatment groups. However, when adjusted for discharge delays, mean
      length of stay for patients in the hospitalist model of care was shorter (5.1
      days vs. 5.6 days; difference, -0.5 day [CI, -0.8 to -0.1 day]). Total costs did
      not differ between groups. Orthopedic surgeons and nurses preferred the
      hospitalist model. LIMITATIONS: Care providers and patients were aware of
      intervention assignments, and the study could not capture all costs associated
      with the hospitalist model. CONCLUSIONS: The comanagement medical Hospitalist
      Orthopedic Team model reduced minor postoperative complication rates with no
      statistically significant difference in length of stay or cost. The nurses and
      surgeons strongly preferred the comanagement hospitalist model. Additional
      research on the clinical and economic impact of the hospitalist model in other
      surgical populations is warranted.

PMID- 15238369
TI  - ALLHAT: setting the record straight.
AB  - The findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent
      Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and
      researchers, including a recent commentary in this journal. Such response was
      expected for a trial of ALLHAT's size and scope, especially since its results
      challenged some widely held beliefs. This paper reviews key aspects of the ALLHAT
      design, analyses, findings, and conclusions to provide a perspective on the
      commentary about the trial's results and implications for clinical practice.
      Several of the most frequent comments regarding the study's results are
      addressed, particularly with respect to heart failure and diabetes outcomes.
      Responses to these comments reinforce the investigators' original conclusion that
      thiazide-type diuretics should remain the preferred first-step drug class for
      treating hypertension and should generally be a part of any multidrug regimen.

PMID- 15238370
TI  - Meta-analysis: the effect of steroids on survival and shock during sepsis depends
      on the dose.
AB  - BACKGROUND: Previous meta-analyses demonstrated that high-dose glucocorticoids
      were not beneficial in sepsis. Recently, lower-dose glucocorticoids have been
      studied. PURPOSE: To compare recent trials of glucocorticoids for sepsis with
      previous glucocorticoid trials. DATA SOURCES: Systematic MEDLINE search for
      studies published between 1988 and 2003. STUDY SELECTION: Randomized, controlled
      trials of sepsis that examined the effects of glucocorticoids on survival or
      vasopressor requirements. DATA EXTRACTION: Two investigators independently
      collected data on patient and study characteristics, treatment interventions, and
      outcomes. DATA SYNTHESIS: The 5 included trials revealed a consistent and
      beneficial effect of glucocorticoids on survival (I2 = 0%; relative benefit,
      1.23, [95% CI, 1.01 to 1.50]; P = 0.036) and shock reversal (I2 = 0%; relative
      benefit, 1.71 [CI, 1.29 to 2.26]; P < 0.001). These effects were the same
      regardless of adrenal function. In contrast, 8 trials published before 1989
      demonstrated a survival disadvantage with steroid treatment (I2 = 14%; relative
      benefit, 0.89 [CI, 0.82 to 0.97]; P = 0.008). In comparison with the earlier
      trials, the more recent trials administered steroids later after patients met
      enrollment criteria (median, 23 hours vs. <2 hours; P = 0.02), for longer courses
      (6 days vs. 1 day; P = 0.01), and in lower total dosages (hydrocortisone
      equivalents, 1209 mg vs. 23 975 mg; P = 0.01) to patients with higher control
      group mortality rates (mean, 57% vs. 34%; P = 0.06) who were more likely to be
      vasopressor-dependent (100% vs. 65%; P = 0.03). The relationship between steroid
      dose and survival was linear, characterized by benefit at low doses and
      increasing harm at higher doses (P = 0.02). LIMITATIONS: We could not analyze
      time-related improvements in medical care and potential bias secondary to
      nonreporting of negative study results. CONCLUSIONS: Although short courses of
      high-dose glucocorticoids decreased survival during sepsis, a 5- to 7-day course
      of physiologic hydrocortisone doses with subsequent tapering increases survival
      rate and shock reversal in patients with vasopressor-dependent septic shock.

PMID- 15238371
TI  - Evaluation of primary care patients with chronic stable angina: guidelines from
      the American College of Physicians.
AB  - In 1999, the American College of Physicians (ACP), then the American College of
      Physicians-American Society of Internal Medicine, and the American College of
      Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the
      management of patients with chronic stable angina. The ACC/AHA then published an
      updated guideline in 2002, which the ACP recognized as a scientifically valid
      review of the evidence and background paper. This ACP guideline summarizes the
      recommendations of the 2002 ACC/AHA updated guideline and underscores the
      recommendations most likely to be important to physicians seeing patients in the
      primary care setting. This guideline is the first of 2 that will provide guidance
      on the management of patients with chronic stable angina. This document will
      cover diagnosis and risk stratification for symptomatic patients who have not had
      an acute myocardial infarction or revascularization procedure in the previous 6
      months. Sections addressing asymptomatic patients are also included. Asymptomatic
      refers to patients with known or suspected coronary disease based on history or
      on electrocardiographic evidence of previous myocardial infarction, coronary
      angiography, or abnormal results on noninvasive tests. A future guideline will
      cover pharmacologic therapy and follow-up.

PMID- 15238372
TI  - Hand hygiene--of reason and ritual.

PMID- 15238373
TI  - The hospitalist joins the surgical team.

PMID- 15238374
TI  - Physicians should administer low-dose corticosteroids selectively to septic
      patients until an ongoing trial is completed.

PMID- 15238375
TI  - Publishing commentary by authors with potential conflicts of interest: when, why,
      and how.

PMID- 15238376
TI  - Innocent.

PMID- 15238377
TI  - Off-service.

PMID- 15238378
TI  - Prevention of hepatocellular carcinoma.

PMID- 15238379
TI  - Atorvastatin-induced polyneuropathy.

PMID- 15238380
TI  - ALLHAT, or the soft science of the secondary end point.

PMID- 15238381
TI  - Managing patients with nonvariceal upper gastrointestinal bleeding.

PMID- 15238382
TI  - Managing patients with nonvariceal upper gastrointestinal bleeding.

PMID- 15238383
TI  - Managing patients with nonvariceal upper gastrointestinal bleeding.

PMID- 15238384
TI  - Screening for family and intimate partner violence.

PMID- 15238385
TI  - Screening for family and intimate partner violence.

PMID- 15238386
TI  - The crucial link between literacy and health.

PMID- 15238387
TI  - Screening for family violence: what's an evidence-based doctor to do?

PMID- 15238388
TI  - Screening for family and intimate partner violence.

PMID- 15238389
TI  - Successful management with intravenous immunoglobulins of acquired von Willebrand
      disease associated with monoclonal gammopathy of undetermined significance.

PMID- 15238390
TI  - Summaries for patients. Hand-washing practices and beliefs of physicians.

PMID- 15238391
TI  - Summaries for patients. A possible new test for diagnosing sepsis.

PMID- 15238392
TI  - Summaries for patients. Cephalosporin allergy in patients with penicillin
      allergy.

PMID- 15238393
TI  - Summaries for patients. Ginseng reduces the effect of warfarin in a study of
      healthy volunteers.

PMID- 15238394
TI  - Summaries for patients. Team care by hospitalists with surgeons after hip or knee
      surgery.

PMID- 15238395
TI  - Summaries for patients. Low doses of steroids improve survival in patients with
      septic shock.

PMID- 15238396
TI  - Summaries for patients. Diagnosis and evaluation of patients with chronic stable
      angina: recommendations from the American College of Physicians.

PMID- 15238397
TI  - Impact of ALLHAT on the role of angiotensin-converting enzyme inhibitors in the
      primary prevention of heart failure.

PMID- 15238398
TI  - Is there a benefit in promoting the concept of radiation risk?

PMID- 15238399
TI  - Non-pulsatile hepatic and portal vein waveforms in patients with liver cirrhosis:
      concordant and discordant relationships.
AB  - The relationship between hepatic vein waveform and portal vein waveform (HVW and
      PVW) was evaluated in 54 healthy subjects and 148 patients with liver cirrhosis
      and portal hypertension using spectral Doppler ultrasound recordings. In all
      healthy subjects, the HVW was triphasic and the PVW was slightly pulsatile. 51 of
      148 patients (34.5%) had flat non pulsatile HVW with a significantly higher
      incidence in Child C vs Child A patients (48.9% vs 20.7%, respectively; p<0.01)
      while 56 of 148 patients (37.8%) had flat PVW, also with significantly higher
      incidence in Child C vs Child A patients (46.7% vs 25.9%, respectively; p<0.05).
      Of the 86 patients having flat waves (HVW or PVW), only 21 (24.4%) had concordant
      flat waves (flat both HVW and PVW) while discordance was detected in the
      remaining 75.6% patients. Only 22 patients (14.9%) had a triphasic HVW but with
      broad spectrum and absent window in 20 (90.9%) and significantly lower pre
      systolic:systolic (PS) ratio (Vmax of the pre-systolic retrograde wave/Vmax of
      the systolic antegrade wave) compared with healthy subjects (0.23+/-0.1 vs 0.42+/
      0.18, respectively; p<0.001). In conclusion, spectral broadening with window
      absence and dampening of the retrograde pre-systolic wave mark are the earliest
      changes in HVW in cirrhotic patients even in the presence of a triphasic pattern.
      The transmission of hepatic vein pulsatility is not a major factor responsible
      for portal vein pulsatility.

PMID- 15238400
TI  - Re-circulation artefact at the carotid bulb can be differentiated from true
      stenosis.
AB  - Re-circulation artefact developing secondary to vortex flow at the bulb of the
      internal carotid artery is very difficult to distinguish from true stenotic
      defect on two-dimensional Fourier transformed time-of-flight magnetic resonance
      angiography (2D-FT TOF MRA). The purpose of our study is to identify appropriate
      distinguishing features of re-circulation artefact. We included 45 extracranial
      carotid arteries collected from 25 patients who underwent both 2D-FT TOF MRA and
      contrast medium based angiography. Review of the 45 vessels demonstrated re
      circulation artefact in 21 vessels, true stenotic defect in 8 vessels, and no
      filling defect in 16 vessels on 2D-FT TOF MRA. We compared the findings of re
      circulation artefact and true stenotic defect in 29 vessels excluding the 16
      vessels without filling defect. The following were evaluated: (1) preservation of
      posterior wall contour; (2) marginal character of filling defect; (3) darkness of
      filling defect; (4) involvement of common carotid artery by filling defect; (5)
      size of filling defect. In four out of the five evaluated items, statistically
      significant difference was present between re-circulation artefact group and true
      stenotic defect group (p<0.01 in all four items, chi(2) analysis). Re-circulation
      artefact demonstrated the preservation of the posterior wall contour (19/21), ill
      defined margin (19/21), less dark defect (18/21), and no involvement of the
      common carotid artery (19/21). On the contrary true stenotic defect demonstrated
      focal loss of posterior wall contour (8/8), sharp margin (8/8), dark defect
      (8/8), and involvement of common carotid artery (4/8). No significant difference
      was noted in the size of the defect between the two groups (p>0.05). The
      specificity of 2D-FT TOF MRA for carotid stenosis was markedly increased after
      application of above signs. These distinguishing signs are very helpful in
      differentiating re-circulation artefact from true stenotic defect.

PMID- 15238401
TI  - Assessment of effective dose from concomitant exposures required in verification
      of the target volume in radiotherapy.
AB  - The requirement of the Ionising Radiation (Medical Exposure) Regulation 2000
      [IR(ME)R] of justifying all exposures to ionizing radiation includes those from
      radiotherapy double exposure portal images resulting in exposure to normal
      tissues outside the treatment volume. Typical effective doses were calculated for
      a range of common sites using CT data to outline those parts of specific organs
      subject to concomitant radiation and generate dose-volume histograms. The product
      of the mean dose and the relative probability of inducing a fatal cancer in
      specific organs was used to determine a representative total effective dose in
      mSv per monitor unit for each site. A table of representative effective doses,
      ranging from 0.32 mSv to 2.56 mSv per monitor unit, was produced, which may be
      used to monitor cumulative effective doses of individual patients from double
      exposure portal images, in addition to those received from localization
      procedures.

PMID- 15238402
TI  - Comparison of a conventional and a flat-panel digital system in interventional
      cardiology procedures.
AB  - The purpose of the study was to analyse the technical characteristics of a newly
      installed flat-panel fluoroscopy (FPF) system in an interventional cardiology
      (IC) department and compare it with an older conventional system. A patient
      survey was performed to investigate the radiation doses delivered by the X-ray
      systems. Finally, methods of technique optimization regarding the new digital
      system were investigated. Dose rates in all fluoroscopic and cine modes were
      measured and image quality assessed using a dedicated test tool. 200 patients
      were investigated, half using the conventional and half using the digital FPF
      system. Patient data collected were: sex, age, weight, height, dose-area product
      (DAP), fluoroscopy time (T) and total number of frames (F). Our results are: (1)
      Digital FPF system: high contrast resolution (HCR) is not affected by
      fluoroscopic mode, whereas low contrast resolution (LCR) is slightly decreased in
      the low mode. (2) The digital FPF system has 2.5 times better HCR than the
      conventional system, with 5 times lower dose in the fluoroscopy mode. (3) Median
      values of DAP, T and F, respectively, in coronary angiography (CA) are: 27.7
      Gycm(2), 4.1 min and 876 for the digital and 39.3 Gycm(2), 5.3 min and 1600 for
      the conventional system. Median values for percutaneous transluminal coronary
      angioplasty (PTCA) are: 51.1 Gycm(2), 12.7 min and 1184 for the digital and 44.3
      Gycm(2), 7.4 min and 1936 for the conventional system. Digital DAP in CA is
      reduced by 30%, suggesting that a dose reduction in the FPF system is possible.
      The results of the study concerning the FPF system lead to the conclusion that
      the lowest fluoroscopic mode and the lowest frame rate should be used in routine
      practice.

PMID- 15238403
TI  - Inverse planning in three-dimensional conformal and intensity-modulated
      radiotherapy of mid-thoracic oesophageal cancer.
AB  - The aim of this study is to demonstrate the use of inverse planning in three
      dimensional conformal radiation therapy (3DCRT) of oesophageal cancer patients
      and to evaluate its dosimetric results by comparing them with forward planning of
      3DCRT and inverse planning of intensity-modulated radiotherapy (IMRT). For each
      of the 15 oesophageal cancer patients in this study, the forward 3DCRT, inverse
      3DCRT and inverse IMRT plans were produced using the FOCUS treatment planning
      system. The dosimetric results and the planner's time associated with each of the
      treatment plans were recorded for comparison. The inverse 3DCRT plans showed
      similar dosimetric results to the forward plans in the planning target volume
      (PTV) and organs at risk (OARs). However, they were inferior to that of the IMRT
      plans in terms of tumour control probability and target dose conformity.
      Furthermore, the inverse 3DCRT plans were less effective in reducing the
      percentage lung volume receiving a dose below 25 Gy when compared with the IMRT
      plans. The inverse 3DCRT plans delivered a similar heart dose as in the forward
      plans, but higher dose than the IMRT plans. The inverse 3DCRT plans significantly
      reduced the operator's time by 2.5 fold relative to the forward plans. In
      conclusion, inverse planning for 3DCRT is a reasonable alternative to the forward
      planning for oesophageal cancer patients with reduction of the operator's time.
      However, IMRT has the better potential to allow further dose escalation and
      improvement of tumour control.

PMID- 15238404
TI  - Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron
      capture therapy and its toxicity and biodistribution in tumour-bearing mice.
AB  - Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic
      carborane-containing porphyrin that has safely delivered high concentrations of
      boron for experimental boron neutron capture therapy (BNCT). Copper
      octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of
      CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied
      in our laboratory, which could possess comparable or better tumour-targeting
      properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics
      and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell)
      carcinomas were compared with those of CuTCPH. The administration of
      approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections
      over 2 days had no apparent effect, but administration of approximately 400 mg
      kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase
      activities in blood plasma, and depressed blood platelet counts for several days.
      Enzymes and platelets returned to normal within 5 days after those injections and
      body weights returned to normal within 2 weeks. High average concentrations of
      boron from either porphyrin were achieved in the two tumour models from a total
      dose of approximately 200 mg kg(-1). The high tumour boron concentration
      decreased slowly while concentrations in blood decreased rapidly. Boron
      concentrations in brain and skin were consistently lower than in tumour by a
      factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with
      (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be
      labelled by (76)Br, another PET-imageable nuclide.

PMID- 15238405
TI  - Adding concurrent low dose continuous infusion of cisplatin to radiotherapy in
      locally advanced cervical carcinoma: a prospective randomized pilot study.
AB  - The tolerability and efficacy of the continuous infusion of cisplatin during
      radiotherapy was studied by tumour response, survival and pelvic control, in
      carcinoma of the cervix. 44 patients with stage IIB-IIIB cervical carcinoma were
      prospectively randomized into two groups: radiation alone (control group) versus
      radiation plus cisplatin (study group). While there was no significant difference
      in diarrhoea and urinary complication scores, emesis and appetite changes were
      significantly greater in the study group. Tumour responses were no different at
      the end of the treatment and 3 months after completion of treatment. After 40
      months median follow-up, 40/44 patients were assessed (one had a second primary
      tumour and three were lost to follow-up). Persistent disease was found in 3
      patients: one in the study arm and two in the control arm. Recurrence was seen in
      10 patients in the first 2 years. 5-year pelvic control rates were; 69.4% and
      63.9% (p=0.7), survival rates were 52.0% and 48.9% (p=0.7) and disease-free
      survival rates were 67.5% and 58.7% (p=0.3) for the control and the study groups,
      respectively. Although the continuous infusion of cisplatin during radiotherapy
      was well tolerated, this additional treatment did not appear to show an
      improvement in pelvic control, survival, or disease-free survival.

PMID- 15238406
TI  - A feasibility study on the prediction of tumour location in the lung from skin
      motion.
AB  - The system for predicting tumour location from skin motion induced by respiration
      was designed to reduce the effects of target movement. Fluoroscopic studies on 34
      sites in the lungs and 14 sites in the diaphragm were performed so that the
      motions of skin markers and organs could be observed simultaneously. While
      patients were lying down in the simulator with radio-opaque markers on their
      skin, fluoroscopic images both in the anterior-posterior (AP) view and in the
      lateral view were sent to an analysing computer and recorded. The results that
      showed a strong correlation (0.77+/-0.12) between the patients' skin and tumour
      movement, especially for the sites located in the lower lung fields or in the
      diaphragm. With the prediction from skin motion, the uncertainties of the
      position of tumours due to respiratory movement could be reduced by up to 1.47 cm
      in the lower lung fields in the superior-inferior (SI) direction. This study
      revealed that it is possible to trace the exact location of tumours in the lungs
      by observing skin motion in most cases (up to 88%).

PMID- 15238407
TI  - Application of low dose rate pulsed fluoroscopy in cardiac pacing and
      electrophysiology: patient dose and image quality implications.
AB  - The performance of a low dose rate pulsed fluoroscopy option and its successful
      application to cardiac pacing and electrophysiology is reported. Low dose rate
      6.25 frames per second pulsed fluoroscopy was made available in two catheter
      laboratories at a specialist cardiac centre in February 2003, and was adopted as
      the standard imaging technique for cardiac pacing procedures. The image quality
      was found to be considerably poorer than conventional modern units, being very
      similar to that which would have been accepted as adequate performance 20 years
      ago, but at less than one-tenth of the dose rate. No problems with the clinical
      acceptance of this imaging mode for cardiac pacing and electrophysiology have
      been reported. The already low median patient dose-area product for pacing at
      this cardiac centre was further reduced by 50% with the introduction of this
      fluoroscopy option.

PMID- 15238408
TI  - Vascular lesions of parotid gland in adult patients: diagnosis with high
      resolution ultrasound and MRI.
AB  - Three adult patients with rare vascular lesions in the parotid gland including
      pseudoaneurysm, arteriovenous fistula and haemangioma are discussed. All patients
      presented with non-specific unilateral parotid mass. In all cases high-resolution
      ultrasound and MRI allowed accurate diagnosis and delineation of the extent of
      lesion. Conventional angiogram was utilized for planning definitive surgical or
      endovascular treatment.

PMID- 15238409
TI  - Use of colour duplex ultrasound to diagnose giant cell arteritis in a case of
      visual loss of uncertain aetiology.
AB  - Giant cell arteritis is a common condition that can result in permanent visual
      loss. It has traditionally been diagnosed by invasive temporal artery biopsy in
      cases of clinical suspicion. The findings of colour duplex ultrasound have
      recently been described. We report the use of duplex ultrasound to diagnose
      temporal arteritis, with clinicopathological correlation, and discuss the
      possible application of this non-invasive technique to the management of giant
      cell arteritis.

PMID- 15238410
TI  - Aneurysmal bone cyst of the sternum: a case report of successful treatment with
      radiotherapy.
AB  - An unusual case of a lytic, expanding lesion of the manubrium with histological
      diagnosis of aneurysmal bone cyst in a 13-year-old girl is presented. After a
      recurrence following primary surgery, the patient was treated successfully by
      external beam radiotherapy. A total dose of 25.2 Gy was delivered using
      conventional fractionation (1.8 Gy day(-1)) to the whole sternum. She remains
      recurrence- and symptom-free 46 months after the end of the treatment. This is
      the sixth patient with primary aneurysmal bone cyst in the sternal region, the
      first paediatric patient for this location, and the first case of its kind
      treated exclusively by radiotherapy ever reported in the literature. The
      histopathological, radiological and clinical findings of the patient are
      presented, relevant literature is reviewed, and radiotherapeutic management of
      such lesions is discussed.

PMID- 15238411
TI  - Endovascular management of multiple arterial aneurysms in Behcet's disease.
AB  - We report a case of Behcet's disease complicated by four arterial aneurysms
      successfully treated by coil embolisation and stent placement. Percutaneous
      endovascular repair offers a safe alternative to surgical management of this
      serious condition.

PMID- 15238412
TI  - Transpleural ultrasound diagnosis of a pulmonary arteriovenous malformation.
AB  - Pulmonary arteriovenous malformations (PAVMs) are rare. We discuss a case of an
      81-year-old female who attended hospital with a haemothorax. Ultrasound not only
      demonstrated an echogenic effusion in the right pleural space, but also
      identified an associated tubular structure. Doppler was applied to this
      structure, which exhibited pulsatile flow. This raised the possibility of a PAVM,
      which was subsequently confirmed on CT and angiography. Although, PAVM is a rare
      cause of haemothorax, the diagnosis should still be considered and transpleural
      ultrasound can detect these malformations non-invasively by the bedside.

PMID- 15238413
TI  - Pulmonary haemangiosarcoma with main pulmonary artery thrombosis imitating
      subacute pulmonary embolism with infarction.
AB  - We report a patient with subacute pulmonary hypertension caused by unilateral
      massive pulmonary artery thrombosis due to a pulmonary haemangiosarcoma of the
      lower lobe with pulmonary arterial and bronchial invasion. The patient was
      misdiagnosed as having subacute pulmonary embolism and underwent thrombolytic
      therapy complicated by severe pulmonary haemorrhage. The imaging features of
      pulmonary artery thrombosis with underlying malignancy and their differential
      diagnosis are discussed.

PMID- 15238414
TI  - A patient with prolonged fever after pharyngotonsillitis.

PMID- 15238415
TI  - Prognostic and biologic significance of chromosomal imbalances assessed by
      comparative genomic hybridization in multiple myeloma.
AB  - Cytogenetic abnormalities, evaluated either by karyotype or by fluorescence in
      situ hybridization (FISH), are considered the most important prognostic factor in
      multiple myeloma (MM). However, there is no information about the prognostic
      impact of genomic changes detected by comparative genomic hybridization (CGH). We
      have analyzed the frequency and prognostic impact of genetic changes as detected
      by CGH and evaluated the relationship between these chromosomal imbalances and
      IGH translocation, analyzed by FISH, in 74 patients with newly diagnosed MM.
      Genomic changes were identified in 51 (69%) of the 74 MM patients. The most
      recurrent abnormalities among the cases with genomic changes were gains on
      chromosome regions 1q (45%), 5q (24%), 9q (24%), 11q (22%), 15q (22%), 3q (16%),
      and 7q (14%), while losses mainly involved chromosomes 13 (39%), 16q (18%), 6q
      (10%), and 8p (10%). Remarkably, the 6 patients with gains on 11q had IGH
      translocations. Multivariate analysis selected chromosomal losses, 11q gains,
      age, and type of treatment (conventional chemotherapy vs autologous
      transplantation) as independent parameters for predicting survival. Genomic
      losses retained the prognostic value irrespective of treatment approach.
      According to these results, losses of chromosomal material evaluated by CGH
      represent a powerful prognostic factor in MM patients.

PMID- 15238416
TI  - Differential expression of granzymes A and B in human cytotoxic lymphocyte
      subsets and T regulatory cells.
AB  - Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the
      perforin/granzyme pathway as a major mechanism to kill pathogen-containing cells
      and tumor cells.(1,2) Dysregulation of this pathway results in several human
      diseases, such as hemophagocytic lymphohistiocytosis. Here we characterize the
      single-cell expression pattern of granzymes A and B in human lymphocytes using a
      flow cytometry-based assay. We demonstrate that most circulating CD56(+)8(-) NK
      cells, and approximately half of circulating CD8(+) T lymphocytes, coexpressed
      both granzymes A and B. In contrast, few circulating CD4(+) T lymphocytes
      expressed granzymes A or B. Activation of CD8(+) T lymphocytes with concanavalin
      A (ConA)/interleukin-2 (IL-2), and activation of CD4(+) T lymphocytes with
      antibodies to CD3/CD28 or CD3/CD46 (to generate T regulatory [Tr1] cells),
      induced substantial expression of granzyme B, but not granzyme A. Naive
      CD4(+)CD45RA(+) cells stimulated with antibodies to CD3/CD46 strongly expressed
      granzyme B, while CD3/CD28 stimulation was ineffective. Finally, we show that
      granzyme B-expressing CD4(+) Tr1 cells are capable of killing target cells in a
      perforin-dependent, but major histocompatibility complex (MHC)/T-cell receptor
      (TCR)-independent, manner. Our results demonstrate discordant expression of
      granzymes A and B in human lymphocyte subsets and T regulatory cells, which
      suggests that different granzymes may play unique roles in immune system
      responses and regulation.

PMID- 15238417
TI  - Eradication of B-CLL by autologous and allogeneic host nonreactive anti-third
      party CTLs.
AB  - Establishment of cell lines capable of killing leukemia cells, in the absence of
      alloreactivity against normal host cells, represents a most desirable goal in
      bone marrow transplantation (BMT) and cancer immunotherapy. By using a human -->
      mouse chimeric model, we demonstrate that allogeneic anti-third-party cytotoxic T
      lymphocytes (CTLs) depleted of alloreactivity are endowed with a potent anti-B
      cell chronic lymphocytic leukemia (B-CLL) reactivity. Likewise, CTL preparations
      generated from autologous T cells of the same patients with B-CLL exhibited
      comparable leukemia eradication, suggesting that the reactivity of allogeneic
      anti-third-party CTLs is not mediated by residual antihost clones. This
      specificity was also exhibited in vitro, and annexin staining revealed that B-CLL
      killing is mediated by apoptosis. While the CTLs killing of third-party cells
      could be blocked by anti-CD3 antibody, the lysis of the B-CLL cells was not
      inhibited by this antibody, suggesting a T-cell receptor (TCR)-independent
      cytotoxicity. The role of cell contact leading to apoptosis of B-CLL cells is
      shown in transwell plates and by anti-lymphocyte function-associated antigen-1
      (LFA-1)-blocking antibody. Up-regulation of CD54 and the subsequent apoptosis of
      B-CLL cells depend on the initial LFA-1/ICAM-1 (intercellular adhesion molecule
      1) interaction. Taken together, these results suggest that allogeneic or
      autologous host nonreactive anti-third-party CTLs may represent a new therapeutic
      approach for patients with B-CLL.

PMID- 15238418
TI  - Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell
      lymphoma (DLBCL) patients with poor outcome.
AB  - FOXP1 (Forkhead box-P1) is a winged-helix transcription factor that is
      differentially expressed in resting and activated B cells. FOXP1 expression has
      been demonstrated in a subset of diffuse large B-cell lymphomas (DLBCLs) and is
      more common in the nongerminal center (non-GC), activated B-cell type; however,
      its prognostic significance is uncertain. We analyzed presentation lymph nodes
      from 126 patients with nodal DLBCL, previously classified according to GC and
      BCL2 status, for FOXP1 protein expression using standard immunocytochemistry.
      Uniform high FOXP1 expression was demonstrated in 23 of 126 patients with DLBCL.
      This high level of expression was almost exclusively confined to patients who
      lacked the GC phenotype, who expressed MUM-1 and BCL2 in the absence of t(14;
      18), and who were identified as a subgroup of patients with particularly poor
      outcomes in a group with already poor prognoses. The data presented suggest that
      high FOXP1 expression is an independent prognostic factor in DLBCL.

PMID- 15238419
TI  - Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect.
AB  - The erythroid defect in Diamond Blackfan anemia (DBA) is known to be intrinsic to
      the stem cell, but its molecular pathophysiology remains obscure. Using a 2-phase
      liquid erythroid culture system, we have demonstrated a consistent defect in DBA,
      regardless of clinical severity, including 3 first-degree relatives with normal
      hemoglobin levels but increased erythrocyte adenosine deaminase activity. DBA
      cultures were indistinguishable from controls until the end of erythropoietin
      (Epo)-free phase 1, but failed to demonstrate the normal synchronized wave of
      erythroid expansion and terminal differentiation on exposure to Epo.
      Dexamethasone increased Epo sensitivity of erythroid progenitor cells, and
      enhanced erythroid expansion in phase 2 in both normal and DBA cultures. In DBA
      cultures treated with dexamethasone, Epo sensitivity was comparable to normal,
      but erythroid expansion remained subnormal. In clonogenic phase 2 cultures, the
      number of colonies did not significantly differ between normal cultures and DBA,
      in the presence or absence of dexamethasone, and at both low and high Epo
      concentrations. However, colonies were markedly smaller in DBA under all
      conditions. This suggests that the Epo-triggered onset of terminal maturation is
      intact in DBA, and the defect lies down-stream of the Epo receptor, influencing
      survival and/or proliferation of erythroid progenitors.

PMID- 15238420
TI  - Myeloablative radiochemotherapy followed by autologous stem cell transplantation
      in first remission prolongs progression-free survival in follicular lymphoma:
      results of a prospective, randomized trial of the German Low-Grade Lymphoma Study
      Group.
AB  - Conventional chemotherapy has failed to substantially prolong survival for
      patients with advanced follicular lymphoma. To improve outcomes, the German Low
      Grade Lymphoma Study Group (GLSG) initiated a randomized trial to compare the
      effect of potentially curative myeloablative radiochemotherapy followed by
      autologous stem cell transplantation (ASCT) with interferon-alpha (IFN-alpha)
      maintenance therapy in first remission. Three hundred seven patients (younger
      than 60 years) with follicular lymphoma were recruited into the trial from 130
      institutions. After 2 cycles of cyclophosphamide-doxorubicin-vincristine
      prednisone (CHOP) or mitoxantrone-chlorambucil-prednisone (MCP) induction
      chemotherapy, patients were randomly assigned to either the ASCT or the IFN-alpha
      group. The respective therapy was started when patients achieved complete or
      partial remission after induction chemotherapy. Two hundred forty patients with
      follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha. In
      patients who underwent ASCT, the 5-year progression-free survival (PFS) rate was
      64.7%, and in the IFN-alpha arm it was 33.3% (P < .0001). As expected, acute
      toxicity was higher in the ASCT group, but early mortality was below 2.5% in both
      study arms. In this randomized, multicenter trial, high-dose radiochemotherapy
      followed by ASCT significantly improved PFS compared with IFN-alpha in patients
      with follicular lymphoma when applied as consolidation in first remission. Longer
      follow-up is necessary to determine the effect of ASCT on overall survival.

PMID- 15238421
TI  - KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell
      cytotoxicity.
AB  - Natural killer (NK) cell inhibitory receptors play important roles in the
      regulation of target susceptibility to natural killing. Here, we report the
      molecular cloning and functional characterization of a novel NK cell receptor,
      KLRL1, from human and mouse dendritic cells. KLRL1 is a type II transmembrane
      protein with an immunoreceptor tyrosine-based inhibitory motif and a C-type
      lectinlike domain. The KLRL1 gene is located in the central region of the NK gene
      complex in both humans and mice, on human chromosome 12p13 and mouse chromosome
      6F3, adjacent to the other KLR genes. KLRL1 is preferentially expressed in
      lymphoid tissues and immune cells, including NK cells, T cells, dendritic cells,
      and monocytes or macrophages. Western blot and fluorescence confocal microscopy
      analyses indicated that KLRL1 is a membrane-associated glycoprotein, which forms
      a heterodimer with an as yet unidentified partner. Human and mouse KLRL1 are both
      predicted to contain putative immunoreceptor tyrosine-based inhibitory motifs
      (ITIMs), and immunoprecipitation experiments demonstrated that KLRL1 associates
      with the tyrosine phosphatases SHP-1 (SH2-domain-containing protein tyrosine
      phosphatase 1) and SHP-2. Consistent with its potential inhibitory function,
      pretreatment of target cells with human KLRL1-Fc fusion protein enhances NK
      mediated cytotoxicity. Taken together, our results demonstrate that KLRL1 belongs
      to the KLR family and is a novel inhibitory NK cell receptor.

PMID- 15238422
TI  - Susceptibility of human fetal mesenchymal stem cells to Kaposi sarcoma-associated
      herpesvirus.
AB  - Recent reports link Kaposi sarcoma-associated herpesvirus (KSHV) infection of
      bone marrow cells to bone marrow failure and lymphoproliferative syndromes. The
      identity of the infected marrow cells, however, remains unclear. Other work has
      demonstrated that circulating mononuclear cells can harbor KSHV where its
      detection predicts the onset and severity of Kaposi sarcoma. In either setting,
      bone marrow precursors may serve as viral reservoirs. Since mesenchymal stem
      cells (MSCs) in human bone marrow regulate the differentiation and proliferation
      of adjacent hematopoietic precursors, we investigated their potential role in
      KSHV infection. Our results indicate that primary MSCs are susceptible to both
      cell-free and cell-associated KSHV in culture. Moreover, infection persisted
      within nearly half of the cells for up to 6 weeks. Thus, MSCs possess a clear
      capacity to support KSHV infection and warrant further exploration into their
      potential role in KSHV-related human disease.

PMID- 15238423
TI  - GPI-anchor deficiency in myeloid cells causes impaired FcgammaR effector
      functions.
AB  - Signaling by transmembrane immunoglobulin G (IgG)-Fc receptors (FcgammaRs) in
      response to ligand involves association with membrane microdomains that contain
      glycosyl phosphatidylinositol (GPI)-anchored proteins. Recent in vitro studies
      showed enhancement of FcgammaR signaling by forced monoclonal antibody-mediated
      cocrosslinking with various GPI-anchored proteins. Here, the possibility that GPI
      anchored proteins are involved in normal physiologic FcgammaR effector functions
      in response to a model ligand was studied using myeloid-specific GPI-anchor
      deficient mice, generated by Cre-loxP conditional targeting. GPI-anchor-deficient
      primary myeloid cells exhibited normal FcgammaR expression and binding or
      endocytosis of IgG-immune complexes (IgG-ICs). Strikingly, after stimulation with
      IgG-ICs, tumor necrosis factor-alpha release, dendritic cell maturation, and
      antigen presentation were strongly reduced by GPI-anchor deficiency. Tyrosine
      phosphorylation of the FcR gamma-chain in response to IgG-IC was impaired in GPI
      anchor-deficient cells. Myeloid GPI-anchor deficiency resulted in attenuated in
      vivo inflammatory processes during IgG-IC-mediated alveolitis. This study
      provides the first genetic evidence for an essential role of GPI-anchored
      proteins in physiologic FcgammaR effector functions in vitro and in vivo.

PMID- 15238424
TI  - Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma
      xenografts in vivo.
AB  - The role of angiogenesis in lymphoproliferative diseases is not well established.
      We demonstrate here that human lymphoma cells secrete vascular endothelial growth
      factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of
      non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the
      addition of VEGF and was blocked by VEGFR-1- and VEGFR-2-specific antibodies. To
      differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma
      growth, NOD/SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL)
      were treated with species-specific antibodies against human VEGFR-1 (6.12), human
      VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment
      with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established
      DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor
      VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and
      DC101 treatment correlated with increased tumor apoptosis and reduced
      vascularization, respectively, supporting the presence of autocrine VEGFR-1- and
      paracrine VEGFR-2-mediated pathways in lymphomagenesis. Inhibition of paracrine
      VEGF interactions (DC101) in these models was equivalent to their inhibition with
      rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12,
      methotrexate) consistently improved tumor responses over those of single-agent
      therapy. These data support the further clinical development of VEGFR-targeted
      approaches for the therapy of aggressive DLBCL.

PMID- 15238425
TI  - Reactive oxygen species limit neutrophil life span by activating death receptor
      signaling.
AB  - Neutrophils are abundant, short-lived leukocytes, and their death by apoptosis is
      central to hemostasis and the resolution of inflammation, yet the trigger for
      their entry into apoptosis is unknown. We show here that death receptor
      signaling, including CD95 death-inducing signaling complex (DISC) formation and
      caspase 8 activation, occurred early in neutrophil apoptosis. However, death
      receptor ligation was not required for apoptosis, suggesting a novel mechanism
      for caspase 8 activation. We detected ceramide generation and clustering of CD95
      in lipid rafts early in neutrophil apoptosis, and neutrophil apoptosis and
      ceramide generation were both significantly inhibited in acid sphingomyelinase
      knockout (ASM(-/-)) mice compared to wild-type littermates. Further studies
      revealed that ceramide generation, CD95 clustering, and neutrophil apoptosis were
      dependent on reactive oxygen species (ROSs) and were preceded by a fall in
      reduced glutathione levels. We propose that accumulation of ROSs, as a
      consequence of altered redox status, initiates ligand-independent death receptor
      signaling via activation of ASM and clustering of preformed DISC components in
      lipid rafts and is therefore a primary factor limiting neutrophil life span.

PMID- 15238426
TI  - Multistep process through which adenoviral vector vaccine overcomes anergy to
      tumor-associated antigens.
AB  - Our goal in the present work was to characterize the multiple steps involved in
      overcoming the anergy that exists in tumor hosts to tumor-associated antigen
      (TAA). Our studies showed that the subcutaneous injection of the Ad-sig
      TAA/ecdCD40L vector resulted in secretion of the TAA/ecdCD40L protein for at
      least 10 days from infected cells. Binding of the TAA/ecdCD40L protein to
      dendritic cells (DCs) resulted in the induction of CCR-7 chemokine receptor
      expression and cytokine release. This was followed by migration of the DCs to
      regional lymph nodes. Tetramer staining, enzyme-linked immunospot (ELISPOT)
      assay, and cytotoxicity assay all showed that the Ad-sig-TAA/ecdCD40L vector
      increased the levels of splenic CD8(+) T cells specific for the 2 TAAs (human
      MUC1 [hMUC1] and HPV E7) tested. Vaccination with the Ad-sighMUC1/ecdCD40L vector
      suppressed the growth of hMUC1 antigen-positive tumor cells in 100% of the test
      mice that were previously anergic to the hMUC1 antigen. These data suggest that
      Ad-sig-TAA-ecd/ecdCD40L vector injections may be of value in treating the many
      epithelial malignancies in which TAA-like hMUC1 is overexpressed.

PMID- 15238427
TI  - Prevalence of anemia in persons 65 years and older in the United States: evidence
      for a high rate of unexplained anemia.
AB  - Clinicians frequently identify anemia in their older patients, but national data
      on the prevalence and causes of anemia in this population in the United States
      have been unavailable. Data presented here are from the noninstitutionalized US
      population assessed in the third National Health and Nutrition Examination Survey
      (1988-1994). Anemia was defined by World Health Organization criteria; causes of
      anemia included iron, folate, and B(12) deficiencies, renal insufficiency, anemia
      of chronic inflammation (ACI), formerly termed anemia of chronic disease, and
      unexplained anemia (UA). ACI by definition required normal iron stores with low
      circulating iron (less than 60 microg/dL). After age 50 years, anemia prevalence
      rates rose rapidly, to a rate greater than 20% at age 85 and older. Overall,
      11.0% of men and 10.2% of women 65 years and older were anemic. Of older persons
      with anemia, evidence of nutrient deficiency was present in one third, ACI or
      chronic renal disease or both was present in one third, and UA was present in one
      third. Most occurrences of anemia were mild; 2.8% of women and 1.6% of men had
      hemoglobin levels lower than 110 g/L (11 g/dL). Therefore, anemia is common,
      albeit not severe, in the older population, and a substantial proportion of
      anemia is of indeterminate cause. The impact of anemia on quality of life,
      recovery from illness, and functional abilities must be further investigated in
      older persons.

PMID- 15238428
TI  - Protease inhibitors potentiate chemotherapy-induced neutropenia.
AB  - Pharmacokinetic interactions between chemotherapy and highly active
      antiretroviral therapy (HAART) are described, but there are few data on their
      clinical relevance. Patients with systemic AIDS-related non-Hodgkin lymphoma
      (ARL) were treated with concomitant HAART and infusional cyclophosphamide
      doxorubicin-etoposide (CDE) chemotherapy. We compared neutropenia according to
      whether patients received protease inhibitor (PI)-based HAART or non-PI regimens.
      Differences in survival, response rates, immunologic parameters, and virologic
      parameters were also investigated. The day-10 (Mann-Whitney U test; P = .012) and
      day-14 (P = .025) neutrophil counts were significantly lower in patients
      receiving PIs, though there were no differences in the number of days of
      granulocyte colony-stimulating factor (G-CSF) administered between groups (P =
      .16). Grade 3 or 4 infections requiring hospitalization were recorded for a total
      of 58 (31%) of 190 cycles of CDE: 23 (48%) of 48 when prescribed PIs and 35 (25%)
      of 142 with concomitant PI-sparing HAART (chi(2) test; P = .0025). There were no
      statistically significant differences in the response rates, relapse-free
      survival, or disease-free survival between patients receiving PIs and those not
      receiving PIs. PI-based HAART appears to significantly potentiate the
      myelotoxicity of CDE chemotherapy. This potentiation may be a consequence of
      microsomal enzyme inhibition reducing the metabolism of cytotoxics in this
      regimen.

PMID- 15238429
TI  - Association of immune abnormalities with telomere shortening in autosomal
      dominant dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is an inherited bone marrow failure disorder
      characterized by abnormal skin pigmentation and nail dystrophy. We have recently
      described, in 10 members of a large 3-generation family, an autosomal-dominant
      form of DC (AD DC) that is due to a mutation in the gene-encoding human
      telomerase RNA (TERC), resulting in telomere shortening. In studying the
      immunologic consequences of TERC mutations, severe B lymphopenia and decreased
      immunoglobulin M (IgM) levels were noted. T cells were found to overexpress
      senescent markers, including CD57 and Fas receptor, and were moderately reduced
      in cell number. To determine whether these in vivo findings were related to
      cellular replicative defects, short-term cultures of AD DC lymphocytes were
      established to measure proliferation, mitoses, and apoptosis. AD DC lymphocytes
      displayed a markedly reduced proliferative capacity and increased basal apoptotic
      rate. Finally, telomere shortening was most prominent in third-generation
      subjects, and there appeared to be a correlation between telomere length and in
      vivo and in vitro immune findings. In summary, the observed lymphopenia and
      hypogammaglobulinemia in AD DC is likely a consequence of replicative failure and
      premature senescence of lymphocytes, supporting a role of telomerase activity in
      immune homeostasis.

PMID- 15238430
TI  - Suppressed responses to self-triggered sounds in the human auditory cortex.
AB  - Humans are assumed to predict the sensory consequences of their own actions by
      means of forward models that enable discrimination between self-produced and
      external sensory signals. Here we tested whether responses in the human auditory
      cortex would differ to self-triggered versus externally triggered tones. The
      responses were recorded with a whole-scalp neuromagnetometer from 12 healthy
      subjects who either themselves triggered a tone by pressing a button once every 5
      s or passively listened to externally triggered tones, presented in an identical
      sound sequence. Sources of the auditory N100m responses, peaking approximately 90
      ms after sound onset in the supratemporal auditory cortex, were significantly
      weaker to self-triggered than to externally triggered sounds (suppressions 24 +/-
      7% and 18 +/- 4% in the left and right hemispheres, respectively). These results
      support the existence of a forward model that predicts the auditory consequences
      of the subject's own motor acts on the environment--even with a tool--and thereby
      enables discrimination between self-produced and external sounds.

PMID- 15238431
TI  - BDNF locally potentiates GABAergic presynaptic machineries: target-selective
      circuit inhibition.
AB  - Inhibitory neurotransmission is critical for neuronal circuit formation. To
      examine whether inhibitory neurotransmission receives target-selective modulation
      in the long term, we expressed the cDNA of brain-derived neurotrophic factor
      (BDNF), which has been shown to induce the augmentation of GABAergic synapses in
      vivo and in vitro, in a small population of cultured hippocampal neurons. At 48 h
      after transfection, the expression level of glutamic acid decarboxylase 65
      (GAD65), a GABA synthetic enzyme that resides mainly in GABAergic terminals, was
      selectively enhanced around the BDNF-expressing neurons, in comparison with the
      neighboring control neurons interposed between the BDNF-expressing neurons and
      inhibitory neurons. Exogenous BDNF application for 48 h also increased the GAD
      level and enhanced the GABA release probability. These potentiating effects were
      attenuated in inhibitory synapses on neurons expressing a dominant negative form
      of the BDNF receptor (tTrkB). This suggests that postsynaptic BDNF-TrkB signaling
      contributes to the target-selective potentiation of inhibitory presynaptic
      machineries. Since BDNF is expressed in an activity-dependent manner in vivo,
      this selectivity may be one of the key mechanisms by which the independence of
      functional neuronal circuits is maintained.

PMID- 15238432
TI  - Increases in the density of parvalbumin-immunoreactive neurons in anterior
      cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin
      releasing factor in sustained elevation.
AB  - We previously reported synchronization of pyramidal neurons within prefrontal
      cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis
      that cortical synchronization may be related to changes in local GABA signaling,
      we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and
      calretinin (CR) as selective labels for three distinct GABA interneuron classes
      in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a
      selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR
      ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal.
      Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was
      reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus,
      the critical role of DA receptors during AMPH exposure is evident. However, DA
      receptor activation did not appear to account for the PV up-regulation in AMPH
      treated rats at 7 day withdrawal. Significantly higher numbers of pericellular
      basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were
      observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual
      immunofluorescence and confocal microscopy further revealed that CRF-ir puncta
      made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell
      bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals,
      that may be underdetected under normal conditions due to low activity levels, may
      be functionally activated during psychostimulant withdrawal, thereby altering
      local GABAergic signaling.

PMID- 15238433
TI  - Analogical reasoning and prefrontal cortex: evidence for separable retrieval and
      integration mechanisms.
AB  - The present study examined the contributions of prefrontal cortex (PFC)
      subregions to two component processes underlying verbal analogical reasoning:
      semantic retrieval and integration. Event-related functional magnetic resonance
      imaging data were acquired while subjects performed propositional analogy and
      semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1),
      followed by an instructional cue and a second word pair (pair 2). On analogy
      trials, subjects evaluated whether pair 2 was semantically analogous to pair 1.
      On semantic trials, subjects indicated whether the pair 2 words were semantically
      related to each other. Thus, analogy--but not semantic--trials required
      integration across multiple retrieved relations. To identify regions involved in
      semantic retrieval, we manipulated the associative strength of pair 1 words in
      both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative
      strength, consistent with a role in controlled semantic retrieval. Left
      frontopolar cortex was insensitive to associative strength, but was more
      sensitive to integration demands than was aLIPC, consistent with a role in
      integrating the products of semantic retrieval to evaluate whether distinct
      representations are analogous. Right dorsolateral PFC exhibited a profile
      consistent with a role in response selection rather than retrieval or
      integration. These findings indicate that verbal analogical reasoning depends on
      multiple, PFC-mediated computations.

PMID- 15238434
TI  - Dorsal anterior cingulate cortex resolves conflict from distracting stimuli by
      boosting attention toward relevant events.
AB  - In everyday life, we often focus greater attention on behaviorally relevant
      stimuli to limit the processing of distracting events. For example, when
      distracting voices intrude upon a conversation at a noisy social gathering, we
      concentrate more attention on the speaker of interest to better comprehend his or
      her speech. In the present study, we investigated whether dorsal/caudal regions
      of the anterior cingulate cortex (dACC), thought to make a major contribution to
      cognitive control, boost attentional resources toward behaviorally relevant
      stimuli as a means for limiting the processing of distracting events. Sixteen
      healthy participants performed a cued global/local selective attention task while
      brain activity was recorded with event-related functional magnetic resonance
      imaging. Consistent with our hypotheses, greater dACC activity during distracting
      events predicted reduced behavioral measures of interference from those same
      events. dACC activity also differed for cues to attend to global versus local
      features of upcoming visual objects, further indicating a role in directing
      attention toward task-relevant stimuli. Our findings indicate a role for dACC in
      focusing attention on behaviorally relevant stimuli, especially when the
      achievement of our behavioral goals is threatened by distracting events.

PMID- 15238435
TI  - Age- and stage-dependent accumulation of advanced glycation end products in
      intracellular deposits in normal and Alzheimer's disease brains.
AB  - In this immunohistochemical study, the age- and stage-dependent accumulation of
      advanced glycation end-products (AGEs) in Alzheimer's disease (AD) and their
      relation to the formation of neurofibrillary tangles and neuronal cell death was
      investigated. For this purpose, the distribution of AGEs in neurons and glia was
      analyzed in the auditory association area of superior temporal gyrus (Brodmann
      area 22) of young and old non-demented controls and compared with early- and late
      stage AD. A possible co-localization of AGEs with typical hallmarks of AD, such
      as hyperphosphorylated tau (as a marker for disturbed kinase/phosphatase
      activity), nNOS (as a marker for nitroxidative stress) and caspase-3 (as a marker
      of apoptotic cell death), was also investigated. Our results show that the
      percentage of AGE-positive neurons (and astroglia) increase both with age and, in
      AD patients, with the progression of the disease (Braak stages). Interestingly,
      nearly all if those neurons which show diffuse cytosolic AGE immunoreactivity
      also contain hyperphosphoryated tau, suggesting a link between AGE accumulation
      and the formation of early neurofibrillary tangles. Many, but not all, neurons
      show a co-localization of AGEs with other markers of neurodegeneration, such as
      nNOS and caspase-3.

PMID- 15238436
TI  - Male-specific volume expansion of the human hippocampus during adolescence.
AB  - To clarify the developmental brain changes during adolescence, brain morphology
      was compared between healthy younger adolescent and elder adolescent subjects
      using both voxel-based morphometry (VBM) and volumetric region-of-interest (ROI)
      analysis of magnetic resonance imaging (MRI). High-resolution three-dimensional
      MRI scans were acquired in 23 (10 males and 13 females) younger adolescent
      subjects (13-14 years) and 30 (15 males and 15 females) elder adolescent subjects
      (19-21 years). Whole-brain analysis by VBM revealed that the elder adolescent
      subjects had significantly more gray matter in the left medial temporal regions
      than the younger adolescent subjects and significantly less gray matter in the
      left medial frontal region (Brodmann area 6). In the volumetric analysis,
      significantly less cerebral gray matter volume and significantly greater cerebral
      white matter volume were found in elder adolescents compared with younger
      adolescents. The volume of the hippocampus was significantly larger in male elder
      adolescents than in male younger adolescents. The volume of the parahippocampal
      gyrus did not differ between younger and elder adolescent subjects. These results
      suggest a robust maturational process ongoing in the human hippocampus during
      adolescence, especially in males. The possible relevance of these findings to
      progress in myelination and implications in psychiatric disorders were discussed.

PMID- 15238437
TI  - Intracortical responses in human and monkey primary auditory cortex support a
      temporal processing mechanism for encoding of the voice onset time phonetic
      parameter.
AB  - This study tests the hypothesis that temporal response patterns in primary
      auditory cortex are potentially relevant for voice onset time (VOT) encoding in
      two related experiments. The first experiment investigates whether temporal
      responses reflecting VOT are modulated in a way that can account for boundary
      shifts that occur with changes in first formant (F1) frequency, and by extension,
      consonant place of articulation. Evoked potentials recorded from Heschl's gyrus
      in a patient undergoing epilepsy surgery evaluation are examined. Representation
      of VOT varies in a manner that reflects the spectral composition of the syllables
      and the underlying tonotopic organization. Activity patterns averaged across
      extended regions of Heschl's gyrus parallel changes in the subject's perceptual
      boundaries. The second experiment investigates whether the physiological boundary
      for detecting the sequence of two acoustic elements parallels the psychoacoustic
      result of approximately 20 ms. Population responses evoked by two-tone complexes
      with variable tone onset times (TOTs) in primary auditory cortex of the monkey
      are examined. Onset responses evoked by both the first and second tones are
      detected at a TOT separation as short as 20 ms. Overall, parallels between
      perceptual and physiological results support the relevance of a population-based
      temporal processing mechanism for VOT encoding.

PMID- 15238438
TI  - Right temporoparietal cortex activation during visuo-proprioceptive conflict.
AB  - The conflict between vision and proprioception has been proposed to explain why
      healthy subjects perform worse than proprioceptively deafferented patients in
      conditions with optical displacement, e.g. novel mirror drawing. It is not known
      which brain processes depend upon the successful integration of visual and
      proprioceptive information and are therefore impaired when these modalities
      disagree. With fMRI in healthy subjects we compared brain activity across two
      conditions with similar visual and proprioceptive stimulation and similar task
      demands that differed by the congruence of movement showed by the two modalities.
      Subjects felt the passive movement of the right index finger on a rectangular
      field and watched a cursor moving on a computer screen. Cursor and finger
      locations either mapped onto each other (congruent condition) or did not
      (incongruent condition). Monitoring incongruent compared with congruent movement
      activated the premotor area bilaterally and the right temporoparietal junction.
      These brain areas have previously been associated with shifts in the attended
      location in the visual space. These findings suggest an interaction between
      vision and proprioception in orienting to spatial locations.

PMID- 15238439
TI  - Axons in cat visual cortex are topologically self-similar.
AB  - The axonal arbors of the different types of neocortical and thalamic neurons
      appear highly dissimilar when viewed in conventional 2D reconstructions.
      Nevertheless, we have found that their one-dimensional metrics and topologies are
      surprisingly similar. To discover this, we analysed the axonal branching pattern
      of 39 neurons (23 spiny, 13 smooth and three thalamic axons) that were filled
      intracellularly with horseradish peroxidase (HRP) during in vivo experiments in
      cat area 17. The axons were completely reconstructed and translated into
      dendrograms. Topological, fractal and Horton-Strahler analyses indicated that
      axons of smooth and spiny neurons had similar complexity, length ratios (a
      measure of the relative increase in the length of collateral segments as the axon
      branches) and bifurcation ratios (a measure of the relative increase in the
      number of collateral segments as the axon branches). We show that a simple random
      branching model (Galton-Watson process) predicts with reasonable accuracy the
      bifurcation ratio, length ratio and collateral length distribution of the axonal
      arbors.

PMID- 15238440
TI  - What disconnection tells about motor imagery: evidence from paraplegic patients.
AB  - Brain activation during motor imagery has been the subject of a large number of
      studies in healthy subjects, leading to divergent interpretations with respect to
      the role of descending pathways and kinesthetic feedback on the mental rehearsal
      of movements. We investigated patients with complete spinal cord injury (SCI) to
      find out how the complete disruption of motor efferents and sensory afferents
      influences brain activation during motor imagery of the disconnected feet. Eight
      SCI patients underwent behavioral assessment and functional magnetic resonance
      imaging. When compared to a healthy population, stronger activity was detected in
      primary and all non-primary motor cortical areas and subcortical regions. In
      paraplegic patients the primary motor cortex was consistently activated, even to
      the same degree as during movement execution in the controls. Motor imagery in
      SCI patients activated in parallel both the motor execution and motor imagery
      networks of healthy subjects. In paraplegics the extent of activation in the
      primary motor cortex and in mesial non-primary motor areas was significantly
      correlated with the vividness of movement imagery, as assessed by an interview.
      The present findings provide new insights on the neuroanatomy of motor imagery
      and the possible role of kinesthetic feedback in the suppression of cortical
      motor output required during covert movements.

PMID- 15238441
TI  - Time modulated prefrontal and parietal activity during the maintenance of
      integrated information as revealed by magnetoencephalography.
AB  - Using magnetoencephalography, we investigated the spatiotemporal patterns of
      brain magnetic activity responsible for maintaining verbal and spatial
      information in either an integrated or an unintegrated fashion. Considering time
      dimension, we noted a greater activation of a fronto-parietal network in early
      latencies during the maintenance of integrated information, and a different
      pattern during the maintenance of unintegrated material, showing a greater
      activation in a fronto-posterior network in late latencies. The greater
      activation found in certain areas which are traditionally reported as being
      engaged in spatial working memory (i.e. superior frontal gyri, dorsolateral
      prefrontal cortex, superior and inferior parietal lobes) when subjects maintained
      integrated information could be explained by a greater weight of the spatial
      dimension. It is as if words somehow acquired a spatial attribute, thus exerting
      a greater load in a neural network specialized in spatial working memory.
      Alternatively, and not mutually exclusive, we also propose that during the
      maintenance of integrated information the allocation of cognitive resources is
      less interfering than during the maintenance of unintegrated information, making
      it easier.

PMID- 15238442
TI  - Oscillatory brain activity dissociates between associative stimulus content in a
      repetition priming task in the human EEG.
AB  - The retrieval and formation of cortical object representations seem to require
      the activation of neuronal cell assemblies, correlated by synchronized neuronal
      activity in the gamma band range (>20 Hz). In the present electroencephalogram
      (EEG) study we have analysed induced gamma band activity during the repetition of
      familiar (meaningful) and unfamiliar (meaningless) line drawings. Results showed
      a broad posterior distribution of induced gamma band responses (GBRs) after the
      initial presentation of a familiar stimulus. Repeated presentations of the same
      picture resulted in a decrease of GBRs, accompanied by a decrease in the number
      of electrode pairs exhibiting significant phase-locking values. These effects
      might be linked to a 'sharpening' mechanism within a cell assembly representing a
      familiar object. In contrast, the re-presentation of primed unfamiliar stimuli
      was associated with an augmentation of gamma power and an increase in
      significantly phase-locked pairs of electrodes. These findings might be a
      signature of the formation of a new cortical network representing an object.
      Event related potentials (ERPs) showed a decrease in amplitude independent of the
      stimuli's associative content, and, thus, seem to play a complementary role in
      repetition priming as compared to high-frequency brain dynamics.

PMID- 15238443
TI  - The prefrontal cortex shows context-specific changes in effective connectivity to
      motor or visual cortex during the selection of action or colour.
AB  - The role of the prefrontal cortex remains controversial. Neuroimaging studies
      support modality-specific and process-specific functions related to working
      memory and attention. Its role may also be defined by changes in its influence
      over other brain regions including sensory and motor cortex. We used functional
      magnetic imaging (fMRI) to study the free selection of actions and colours.
      Control conditions used externally specified actions and colours. The prefrontal
      cortex was activated during free selection, regardless of modality, in contrast
      to modality-specific activations outside prefrontal cortex. Structural equation
      modelling (SEM) of fMRI data was used to test the hypothesis that although the
      same regions of prefrontal cortex may be active in tasks within different
      domains, there is task-dependent effective connectivity between prefrontal cortex
      and non-prefrontal cortex. The SEM included high-order interactions between
      modality, selection and regional activity. There was greater coupling between
      prefrontal cortex and motor cortex during free selection and action tasks, and
      between prefrontal cortex and visual cortex during free selection of colours. The
      results suggest that the functions of the prefrontal cortex may be defined not
      only by selection-specific rather than modality-specific processes, but also by
      changing patterns of effective connectivity from prefrontal cortex to motor and
      sensory cortices.

PMID- 15238444
TI  - D1 dopamine receptor regulation of the levels of the cell-cycle-controlling
      proteins, cyclin D, P27 and Raf-1, in cerebral cortical precursor cells is
      mediated through cAMP-independent pathways.
AB  - Previously, we demonstrated that dopamine D1 receptor (D1R) agonists inhibit
      epidermal growth factor (EGF)-induced passage of mouse fetal cerebral cortical
      precursor cells from the G1 phase to the S phase of the cell cycle. Here, we
      report that this action of D1R agonists may involve regulation of cyclin D, and
      P27, which respectively promote and suppress the G1 to S transition. Furthermore,
      regulation of Raf-1, a component of the receptor tyrosine kinase mitogen
      activated protein kinase pathway engaged in the mitogenic activity of EGF, may
      also be involved. Specifically, levels of cyclin D and Raf-1 decrease, whereas
      those of P27 first increase and then decrease in a dose-dependent fashion in
      response to the D1R agonist, SKF38393. This agonist also promotes Raf-1
      phosphorylation on serine 338 residue, suggesting increased activation of this
      protein. Only the latter effect can be blocked by adenylyl cyclase (AC) and cAMP
      dependent protein kinase A (PKA) inhibitors, and mimicked by agonists of the cAMP
      signaling pathway. Another D1R agonist, SKF83959, which stimulates phospholipase
      Cbeta (PLCbeta) but not AC, reduces levels of Raf-1 and cyclin D similar to
      SKF38393. However, we detected only down-regulation of P27 by this agonist.
      Additionally, the concentration-dependent patterns of both SKF38393- and SKF83959
      induced alterations in the levels of P27 closely resemble the effects of these
      ligands on the levels of the D1R-PLCbeta-associated second-messenger cascades
      linker, calcyon. These findings suggest that D1R-induced suppression of the cell
      cycle progression in EGF-supported fetal cortical precursor cells represents a
      net effect of competing cell cycle promoting and inhibiting molecular changes,
      which involve cyclin D, P27 and Raf-1. The data also show that cAMP second
      messenger cascade is not engaged in the D1R-induced regulation of the levels of
      these three proteins. Such regulation probably involves PLCbeta-associated
      pathways.

PMID- 15238445
TI  - A study of pyramidal cell structure in the cingulate cortex of the macaque monkey
      with comparative notes on inferotemporal and primary visual cortex.
AB  - Recent studies have revealed a marked degree of variation in the pyramidal cell
      phenotype in visual, somatosensory, motor and prefrontal cortical areas in the
      brain of different primates, which are believed to subserve specialized cortical
      function. In the present study we carried out comparisons of dendritic structure
      of layer III pyramidal cells in the anterior and posterior cingulate cortex and
      compared their structure with those sampled from inferotemporal cortex (IT) and
      the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer
      Yellow in flat-mounted cortical slices, and processed for a light-stable DAB
      reaction product. Size, branching pattern, and spine density of basal dendritic
      arbors was determined, and somal areas measured. We found that pyramidal cells in
      anterior cingulate cortex were more branched and more spinous than those in
      posterior cingulate cortex, and cells in both anterior and posterior cingulate
      were considerably larger, more branched, and more spinous than those in area V1.
      These data show that pyramidal cell structure differs between posterior
      dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in
      cingulate cortex have different structure to those in many other cortical areas.
      These results provide further evidence for a parallel between structural and
      functional specialization in cortex.

PMID- 15238446
TI  - FMRI evidence for activation of multiple cortical regions in the primary auditory
      cortex of deaf subjects users of multichannel cochlear implants.
AB  - To investigate the activation of the auditory cortex by fMRI, three deaf subjects
      users of the Ineraid cochlear implant participated in our study. Possible
      interference between fMRI acquisition and the implanted electrodes was controlled
      and safe experimental conditions were obtained. For each subject, electrical
      stimuli were applied on different intracochlear electrodes, in monopolar mode.
      Stimulation of each electrode was actually producing auditory sensations of
      different pitches, as demonstrated by psychophysical pitch-ranking measurements
      in the same subjects. Because deaf subjects did not hear scanner noise, the data
      were collected in 'silent background' conditions, i.e. as a result of pure
      auditory sensations. Functional maps showed activation of the primary auditory
      cortex, predominantly in the left hemisphere. Stimulation of each different
      intracochlear electrode revealed different clusters of activation. After cluster
      grouping, at least three regions have been identified in the auditory cortex of
      each subject, and comparisons with previous architectonic and functional studies
      are proposed. However, a tonotopic organization could not be clearly identified
      within each region. These arguments, obtained without interference with unwanted
      scanner noise, plead in favor of a functional subdivision of the primary auditory
      cortex into multiple cortical regions in cochlear implant users.

PMID- 15238447
TI  - Functional-anatomical validation and individual variation of diffusion
      tractography-based segmentation of the human thalamus.
AB  - Parcellation of the human thalamus based on cortical connectivity information
      inferred from non-invasive diffusion-weighted images identifies sub-regions that
      we have proposed correspond to nuclei. Here we test the functional and anatomical
      validity of this proposal by comparing data from diffusion tractography,
      cytoarchitecture and functional imaging. We acquired diffusion imaging data in
      eleven healthy subjects and performed probabilistic tractography from voxels
      within the thalamus. Cortical connectivity information was used to divide the
      thalamus into sub-regions with highest probability of connectivity to distinct
      cortical areas. The relative volumes of these connectivity-defined sub-regions
      correlate well with volumetric predictions based on a histological atlas.
      Previously reported centres of functional activation within the thalamus during
      motor or executive tasks co-localize within atlas regions showing high
      probabilities of connection to motor or prefrontal cortices, respectively. This
      work provides a powerful validation of quantitative grey matter segmentation
      using diffusion tractography in humans. Co-registering thalamic sub-regions from
      11 healthy individuals characterizes inter-individual variation in segmentation
      and results in a population-based atlas of the human thalamus that can be used to
      assign likely anatomical labels to thalamic locations in standard brain space.
      This provides a tool for specific localization of functional activations or
      lesions to putative thalamic nuclei.

PMID- 15238448
TI  - Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe
      stimulation in vivo: involvement of serotonin and GABA.
AB  - Serotonin is involved in psychiatric disorders exhibiting abnormal prefrontal
      cortex (PFC) function (e.g. major depression, schizophrenia). We examined the
      effect of the stimulation of the dorsal and median raphe nuclei (DR and MnR,
      respectively) on the activity of PFC neurons. Electrical stimulation of DR/MnR
      inhibited 66% (115/173) of pyramidal neurons in the medial PFC (mPFC). The rest
      of the cases exhibited orthodromic excitations, either pure (13%) or preceded by
      short-latency inhibitions (20%). Excited neurons had a lower pre-stimulus firing
      rate than those inhibited. Excitations evoked by MnR stimulation had a shorter
      latency than those evoked by DR stimulation. WAY-100635 [a 5-hydroxytryptamine1A
      (5-HT1A) antagonist] and the selective gamma aminobutyric acidA (GABAA)
      antagonist picrotoxinin partially antagonized DR/MnR-evoked inhibitions,
      suggesting the involvement of 5-HT1A- and GABAA-mediated components. The presence
      of a direct DR/MnR-mPFC GABAergic component is suggested by the short latency of
      evoked inhibitions (9 +/- 1 ms), faster than those evoked in the secondary motor
      area (20 +/- 3 ms), and that of antidromic spikes evoked by DR/MnR stimulation in
      mPFC pyramidal neurons (15 +/- 1 ms). Stimulation of the DR/MnR with paired
      pulses enhanced the duration of inhibitions and turned some excitations into
      inhibitions. Thus, the DR/MnR control the activity of mPFC pyramidal neurons in
      vivo in a complex manner, involving 5-HT-mediated excitations and GABA- and 5-HT
      mediated inhibitions.

PMID- 15238449
TI  - Synaptic and spiking dynamics underlying reward reversal in the orbitofrontal
      cortex.
AB  - Cognitive and emotional flexibility involve a coordinated interaction between
      working memory, attention, reward expectations, and the evaluation of rewards and
      punishers so that behaviour can be changed if necessary. We describe a model at
      the integrate-and-fire neuronal level of the synaptic and spiking mechanisms
      which can hold an expectation of a reward rule in working memory, and can reverse
      the reward rule if expected rewards are not obtained. An example of a reward rule
      is that stimulus 1 is currently associated with reward, and stimulus 2 with
      punishment. The attractor-based reward rule working memory incorporates a spike
      frequency synaptic adaptation mechanism which supports the neural switching
      between rules by being shut down by a general inhibitory input produced by
      punishment, so that when the attractor starts up again is in the opposite state.
      The mechanism can implement one-trial reward reversal, which is a property of
      orbitofrontal cortex neurons. We show how this reward rule input can operate in a
      biased competition way to influence which one of two stimuli is currently
      associated with reward and which with punishment, and to map the stimuli
      correctly to the reward or punishment representations, providing a basis for
      action selection required to obtain the reinforcer.

PMID- 15238450
TI  - Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is
      fated to become upper cortical layer neurons.
AB  - Projection neurons destined for the cortical plate are generated sequentially
      from the proliferative ventricular and subventricular zones (VZ/SVZ) of the
      pallium. However, the respective contribution of both proliferative zones to the
      generation of cortical plate neurons is better established in humans and non
      human primates than in rodents. We identified Cux2 as a new marker for murine
      cortical subpopulations and used it to provide new insights to the development of
      the mouse cortex. Cux2 is an orthologue of the Drosophila cut gene, which encodes
      a homeodomain protein involved in neuronal specification. During cortical
      development Cux2 identifies two subpopulations with different spatial origins,
      migratory behaviours and phenotypic characteristics: (i) a population of
      interneurons, which invades the pallium from the subpallium; and (ii) a neuronal
      population produced in the pallium around embryonic day 11.5, which divides in
      the SVZ and accumulates in the intermediate zone (IZ). Subsequently, Cux2 is a
      marker of upper cortical layers. Using different molecular markers and Pax6
      deficient mice, we provide data that suggest a relationship between the early
      determined Cux2-positive neuronal precursors in the SVZ/IZ and upper layer
      neurons. This suggests that laminar determination of upper cortical layer neurons
      occurs during the earliest stages of corticogenesis.

PMID- 15238451
TI  - Moderate daily intake of red wine inhibits mural thrombosis and monocyte tissue
      factor expression in an experimental porcine model.
AB  - BACKGROUND: Moderate consumption of red wine has been epidemiologically
      associated with a reduction in cardiovascular disease, but its mechanism of
      action is not fully understood. The objective was to study whether the protective
      effects of a daily intake of red wine (Tempranillo, 12.8% alcohol vol/vol) could
      be related to inhibition of thrombosis in an experimental model of diet-induced
      hyperlipemia. METHODS AND RESULTS: For 100 days, animals were fed a western-type
      proatherogenic diet containing 2% cholesterol and 20% saturated fat. Three doses
      of red wine were studied (20, 30, and 40 g wine-ethanol/d) and compared with
      placebo-control animals not taking any wine. Thrombosis under flow conditions was
      evaluated by radioisotopic quantification of deposited platelets on damaged
      arteries. Changes in RhoA translocation in platelets and monocyte tissue factor
      expression were also analyzed. Mural platelet deposition was significantly
      reduced in animals ingesting red wine with their food. Expression of RhoA in the
      platelet cytoplasm (inactive form) was increased in wine-fed animals. Tissue
      factor mRNA expression in lipopolysaccharide-stimulated monocytes was reduced in
      wine-fed animals. Total cholesterol levels were not significantly different among
      groups. CONCLUSIONS: Moderate red wine intake significantly reduces platelet
      deposition triggered by damaged vessel wall, partially explained by inhibition of
      RhoA translocation to the platelet membrane. Hence, a daily moderate intake of
      wine seems to inhibit different pathways that converge in a reduced thrombotic
      risk on vessel wall injury.

PMID- 15238452
TI  - Aggregated low-density lipoprotein uptake induces membrane tissue factor
      procoagulant activity and microparticle release in human vascular smooth muscle
      cells.
AB  - BACKGROUND: Tissue factor (TF) is the main initiator of the arterial blood
      coagulation system, and aggregated LDL (agLDL) are found in the arterial intima.
      Our hypothesis is that agLDL internalization by vascular smooth muscle cells
      (VSMCs) may trigger TF-procoagulant activity. METHODS AND RESULTS: Cultured human
      VSMCs were obtained from human coronary arteries of explanted hearts during
      transplant operations. VSMCs were incubated with native LDL (nLDL) or agLDL. TF
      mRNA was analyzed by real-time polymerase chain reaction, and cellular and
      released TF protein antigen were analyzed by Western blot. TF microparticle (MP)
      content was analyzed by flow cytometry and TF activity by a factor Xa generation
      test. Both nLDL and agLDL strongly and equally increased TF mRNA and cell
      membrane protein expression, by approximately 5- and 9-fold, respectively. A
      sustained TF procoagulant activity was induced by agLDL but not by nLDL (agLDL
      2.46+/-0.22 versus nLDL 0.72+/-0.12 mU/mg protein at 12 hours). AgLDL increased
      TF antigen release (agLDL 5.64+/-0.4 versus nLDL 3.28+/-0.22 AU) and TF MP
      release (agLDL 89.85+/-8.51 versus nLDL 19.69+/-4.59 TF MP/10(3) cells). TF
      activation and release induced by agLDL is not related to apoptosis. Blockade of
      LDL receptor-related protein, a receptor for agLDL, prevented the agLDL-induced
      release of TF protein and TF MP. CONCLUSIONS: VSMC-TF expression is upregulated
      by both nLDL and agLDL. However, only agLDL engagement to LDL receptor-related
      protein induced cellular TF procoagulant activity and TF release by human VSMCs.

PMID- 15238453
TI  - Serum total and lipoprotein cholesterol levels and awareness, treatment, and
      control of hypercholesterolemia in China.
AB  - BACKGROUND: Cardiovascular disease has become the leading cause of death in
      China. We examined the levels of serum total and lipoprotein cholesterol and
      status of awareness, treatment, and control of hypercholesterolemia in China.
      METHODS AND RESULTS: A cross-sectional survey in a nationally representative
      sample of 15,540 Chinese adults 35 to 74 years of age was conducted during 2000
      to 2001. Serum cholesterol was measured by use of standard methods, and
      information on treatment of hyperlipidemia was obtained by use of a standard
      questionnaire. Age-standardized mean levels of total, HDL, and LDL cholesterol
      and triglycerides were 186.1, 51.7, 109.5, and 128.1 mg/dL, respectively. Of the
      Chinese population 35 to 74 years of age, 23.8% (112,500000 persons) had
      borderline high total cholesterol (200 to 239 mg/dL), and 9.0% (42,540000
      persons) had high total cholesterol (> or =240 mg/dL). The population estimates
      for borderline high (130 to 159 mg/dL), high (160 to 189 mg/dL), and very high (>
      or =190 mg/dL) LDL cholesterol were 17.0% (80,122000 persons), 5.1% (24,329000
      persons), and 2.7% (12,822000 persons), respectively. In addition, 19.2%, or 90
      803 000 persons, had a low HDL cholesterol (<40 mg/dL). Among those who had a
      total cholesterol > or =200 mg/dL or who were on cholesterol-lowering
      medications, the proportion of men and women who were aware, treated, and
      controlled was only 8.8% and 7.5%, 3.5% and 3.4%, and 1.9% and 1.5%,
      respectively. CONCLUSIONS: The prevalence of hypercholesterolemia was relatively
      high and the percentage of adults with controlled blood cholesterol was low in
      China. Prevention and treatment of hypercholesterolemia should be an important
      component of a national strategy to reduce the substantial and increasing burden
      of cardiovascular disease in China.

PMID- 15238454
TI  - Long-term comparison of the implantable cardioverter defibrillator versus
      amiodarone: eleven-year follow-up of a subset of patients in the Canadian
      Implantable Defibrillator Study (CIDS).
AB  - BACKGROUND: The implantable cardioverter defibrillator (ICD) is superior to
      amiodarone for secondary prophylaxis of sudden cardiac death. However, the
      magnitude of this benefit over long-term follow-up is not known. Thus, our
      objective was to evaluate the long-term consequences of using amiodarone versus
      an ICD as first-line monotherapy in patients with a prior history of sustained
      ventricular tachycardia/ventricular fibrillation or cardiac arrest. METHODS AND
      RESULTS: A total of 120 patients were enrolled at St Michael's Hospital in the
      Canadian Implantable Defibrillator Study (CIDS) and were randomly assigned to
      receive either amiodarone (n=60) or an ICD (n=60). The treatment strategy was not
      altered after the end of CIDS unless the initial assigned therapy was not
      effective or was associated with serious side effects. After a mean follow-up of
      5.6+/-2.6 years, there were 28 deaths (47%) in the amiodarone group, compared
      with 16 deaths (27%) in the ICD group (P=0.0213). Total mortality was 5.5% per
      year in the amiodarone group versus 2.8% per year in the ICD group (hazard ratio
      of amiodarone: ICD, 2.011; 95% confidence interval, 1.087 to 3.721; P=0.0261). In
      the amiodarone group, 49 patients (82% of all patients) had side effects related
      to amiodarone, of which 30 patients (50% of all patients) required
      discontinuation or dose reduction; 19 patients crossed over to ICD because of
      amiodarone failure (n=7) or side effects (n=12). CONCLUSIONS: In a subset of
      CIDS, the benefit of the ICD over amiodarone increases with time; most amiodarone
      treated patients eventually develop side effects, have arrhythmia recurrences, or
      die.

PMID- 15238455
TI  - Implantation of immature neonatal cardiac cells into the wall of the aorta in
      rats: a novel model for studying morphological and functional development of
      heart cells in an extracardiac environment.
AB  - BACKGROUND: Morphological and functional development of implanted neonatal
      cardiac cells in the wall of the abdominal aorta in rats was investigated.
      METHODS AND RESULTS: Cardiomyocytes from neonatal Fischer rats (both sexes) or
      medium were injected into the wall of the abdominal aorta in female Fischer rats
      (n=22 in each group). Two or 6 weeks later, the grafted site was exposed and
      fixed for histological and immunohistological examination. Polymerase chain
      reaction analysis of the SRY gene to identify male cells was performed in the
      treated aortas. Seven of 10 cell-treated aortas but none of 10 medium-treated
      aortas showed spontaneous rhythmic beating at the grafted site after excision of
      the heart at 2 weeks. Polymerase chain reaction of the SRY gene was positive in 3
      cell-treated aortas and none of 3 medium-treated aortas at 6 weeks. Hematoxylin
      and-eosin staining showed viable grafts in 9 of 10 aortas at 2 weeks and 9 of 9
      aortas at 6 weeks in the cell-treated group but in none of the aortas receiving
      medium. Neonatal cardiomyocytes in the graft formed compact, longitudinally
      oriented cardiac muscle bundles and had cross-striations and vascularization.
      Immunohistochemical staining for sarcomeric actin was positive in 4 of 10 aortas
      at 2 weeks and 9 of 9 aortas at 6 weeks in the cell group but in none of the
      aortas in the medium group. CONCLUSIONS: Grafted neonatal cardiomyocytes survive,
      differentiate, grow, develop a blood supply, and spontaneously contract within
      the wall of the aorta in rats.

PMID- 15238457
TI  - In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding
      molecular magnetic resonance contrast agent.
AB  - BACKGROUND: The advent of fibrin-binding molecular magnetic resonance (MR)
      contrast agents and advances in coronary MRI techniques offers the potential for
      direct imaging of coronary thrombosis. We tested the feasibility of this approach
      using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX
      Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis.
      METHODS AND RESULTS: Ex vivo and in vivo sensitivity of coronary MR thrombus
      imaging was tested by use of intracoronarily delivered Gd-DTPA-labeled fibrinogen
      thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was
      induced by x-ray-guided placement of thrombogenic-coated, MR-lucent stents (n=5).
      After stent placement, 60 micromol of EP-2104R was injected via the left main
      coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and
      thrombus imaging were performed (1) before and after stent placement and (2)
      before and after EP-2104R. Thrombi were confirmed by x-ray angiography and
      autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled
      fibrinogen clots (approximately 250 micromol/L Gd) were visible on MRI and
      subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent
      thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were
      confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to
      147 micromol/L Gd. CONCLUSIONS: We demonstrate the feasibility of MRI of coronary
      thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR
      contrast agent. Potential applications include detection of coronary in-stent
      thrombosis or thrombus burden in patients with acute coronary syndromes.

PMID- 15238456
TI  - Altered titin expression, myocardial stiffness, and left ventricular function in
      patients with dilated cardiomyopathy.
AB  - BACKGROUND: The role of the giant protein titin in patients with heart failure is
      not well established. We investigated titin expression in patients with end-stage
      heart failure resulting from nonischemic dilated cardiomyopathy, in particular as
      it relates to left ventricular (LV) myocardial stiffness and LV function. METHODS
      AND RESULTS: SDS-agarose gels revealed small N2B (stiff) and large N2BA
      (compliant) cardiac titin isoforms with a mean N2BA:N2B expression ratio that was
      significantly (P<0.003) increased in 20 heart failure patients versus 6 controls.
      However, total titin was unchanged. The coexpression ratio was highest in a
      subsample of patients with an impaired LV relaxation pattern (n=7), intermediate
      in those with pseudonormal filling (n=6), and lowest in the group with
      restrictive filling (n=7). Mechanical measurements on LV muscle strips dissected
      from these hearts (n=8) revealed that passive muscle stiffness was significantly
      reduced in patients with a high N2BA:N2B expression ratio. Clinical correlations
      support the relevance of these changes for LV function (assessed by invasive
      hemodynamics and Doppler echocardiography). A positive correlation between the
      N2BA:N2B titin isoform ratio and deceleration time of mitral E velocity, A wave
      transit time, and end diastolic volume/pressure ratio was found. These changes
      affect exercise tolerance, as indicated by the positive correlation between the
      N2BA:N2B isoform ratio and peak O2 consumption (n=10). Upregulated N2BA
      expression was accompanied by increased expression levels of titin-binding
      proteins (cardiac ankyrin repeat protein, ankrd2, and diabetes ankyrin repeat
      protein) that bind to the N2A element of N2BA titin (studied in 13 patients).
      CONCLUSIONS: Total titin content was unchanged in end-stage failing hearts and
      the more compliant N2BA isoform comprised a greater percentage of titin in these
      hearts. Changes in titin isoform expression in heart failure patients with
      dilated cardiomyopathy significantly impact diastolic filling by lowering
      myocardial stiffness. Upregulation of titin-binding proteins indicates that the
      importance of altered titin expression might extend to cell signaling and
      regulation of gene expression.

PMID- 15238458
TI  - Tissue plasminogen activator antigen and D-dimer as markers for atherothrombotic
      risk among healthy postmenopausal women.
AB  - BACKGROUND: Plasma markers of fibrinolytic function are associated with incident
      coronary events among several, but not all, prospective epidemiologic
      investigations of healthy individuals. Few studies have evaluated this
      relationship in women. In addition, although menopausal hormone therapy (HT) may
      alter markers of fibrinolytic function, the relevance of this effect for coronary
      risk assessment has not been studied. METHODS AND RESULTS: In a prospective,
      nested case-control study among 75 343 postmenopausal women without prior
      cardiovascular disease or cancer, we evaluated the relationships of elevated
      tissue plasminogen activator (tPA) antigen and D-dimer with subsequent first
      coronary heart disease events over a median period of 2.9 years. Baseline levels
      of both biomarkers were higher among 304 cases compared with 304 controls matched
      on age, smoking status, ethnicity, and length of follow-up; median values were
      9.0 versus 7.4 ng/mL (P<0.001) for tPA antigen and 27.6 versus 23.4 ng/mL
      (P=0.001) for D-dimer. In matched-pairs analyses, the odds ratio in the highest
      versus lowest quartile of tPA antigen was 3.5 (95% CI, 2.1 to 5.8; P trend
      <0.001) and for D-dimer was 2.0 (95% CI, 1.2 to 3.2; P trend=0.005). After
      adjustment for lipid and nonlipid risk factors, including C-reactive protein, tPA
      antigen remained a significant predictor. Multivariable-adjusted associations for
      D-dimer, although attenuated, largely remained statistically significant. When
      stratified by HT, the relationship between tPA antigen and incident coronary
      heart disease was similar among nonusers, estrogen-only users, and current users
      of any HT. CONCLUSIONS: Elevated tPA antigen and, to a lesser extent, D-dimer are
      independently associated with incident coronary events among postmenopausal
      women. In analyses stratified by HT, tPA antigen remained a consistent marker of
      increased coronary risk.

PMID- 15238459
TI  - Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a
      prospective, population-based cohort study.
AB  - BACKGROUND: Indicators of carotid atherosclerosis may confer additional
      prognostic value and guide clinicians in cardiovascular risk assessment. Carotid
      artery morphology (plaque burden) and function (stiffness indexes) as predictors
      of all-cause and cardiovascular mortality were prospectively evaluated in elderly
      men. METHODS AND RESULTS: Cardiovascular risk profile was measured in 367
      independently living men (mean+/- SD age, 78+/-4 years). The number of carotid
      plaques was assessed by B-mode ultrasound, and arterial stiffness was quantified
      with a wall tracker system. During 48 months of follow-up, 70 deaths (28
      cardiovascular) occurred. The total number of carotid plaques was the parameter
      most closely related to prognosis. In the age-adjusted multivariate Cox model,
      all-cause mortality was predicted by number of plaques (hazard ratio [HR] per 1
      unit increase, 1.35; 95% confidence interval [CI], 1.12 to 1.64). Predictors of
      cardiovascular mortality in the respective model were number of plaques (HR,
      1.18; 95% CI, 1.04 to 1.33) and Young's elastic modulus (HR, 1.68; 95% CI, 1.26
      to 2.26). Number of plaques improved the prognostic utility in any prognosis
      model when added to commonly available cardiovascular risk information. In
      contrast, stiffness indexes offered no consistent additive value. CONCLUSIONS: In
      elderly men, carotid artery plaque burden is a strong independent predictor of
      all-cause and cardiovascular mortality in the years to come. The additional value
      of carotid artery stiffness measurements as a pathophysiologically related entity
      appears to be limited in this age group and, if anything, confined to
      cardiovascular mortality risk.

PMID- 15238460
TI  - Regression of coronary atherosclerosis by simvastatin: a serial intravascular
      ultrasound study.
AB  - BACKGROUND: Angiography of the coronary arteries reflects only changes in luminal
      dimensions. With intravascular ultrasound, cross-sectional images can be obtained
      and area measurements can be added to calculate volumes of the external elastic
      membrane (EEM), plaque plus media (P+M), and lumen. The aim of this study was to
      investigate the effect of lipid lowering by simvastatin on coronary
      atherosclerotic P+M as changes in volumes of EEM, P+M, and lumen. METHODS AND
      RESULTS: In 40 male patients with hypercholesterolemia, ischemic heart disease,
      and a nonsignificant coronary artery lesion in a not previously revascularized
      coronary artery, serial intravascular ultrasound studies with an ECG-triggered
      pullback were performed at baseline, after 3 months on a lipid-lowering diet, and
      after another 12 months on simvastatin 40 mg/d. Mean length of the analyzed
      atherosclerotic segments was 5.9+/-3.3 mm. After 12 months on simvastatin, a
      significant reduction in P+M volume of 6.3% (P=0.002) was observed, whereas only
      a nonsignificant reduction in EEM volume of 1.8% was seen without any concomitant
      change in lumen volume. A significant reduction in total cholesterol of 31.0%
      (6.1+/-0.8 versus 4.2+/-0.7 mmol/L, P<0.001) and LDL cholesterol of 42.6% (4.0+/
      0.8 versus 2.2+/-0.6 mmol/L, P<0.001) was obtained. CONCLUSIONS: Lipid-lowering
      therapy with simvastatin for 12 months is associated with a significant P+M
      regression in coronary arteries measured as reduction in P+M and EEM volumes
      without any concomitant change in lumen volume.

PMID- 15238461
TI  - Improvement of postnatal neovascularization by human adipose tissue-derived stem
      cells.
AB  - BACKGROUND: Several studies have suggested that stem cells are present in the
      stroma-vascular fraction (SVF) of adipose tissue (AT). METHODS AND RESULTS: To
      characterize the cell populations that compose the SVF of human AT originating
      from subcutaneous and visceral depots, fluorescence-activated cell sorter
      analysis was performed by use of fluorescent antibodies directed against the
      endothelial and stem cell markers CD31, CD34, CD133, and ABCG2. The freshly
      harvested SVF contained large numbers of CD34+ cells as well as cells expressing
      CD133 and ABCG2. Further analysis of the CD34+ cells revealed 2 CD34+ cell
      populations with differential expression of the endothelial cell marker CD31.
      Selection of the CD34+/CD31- cells by use of magnetic microbeads, followed by
      cell culture, demonstrated that this cell population could differentiate under
      appropriate conditions into endothelial cells. Moreover, in mouse ischemic
      hindlimb, intravenous injection of CD34(+)/CD31(-) cells was associated with an
      increase in the blood flow and the capillary density and an incorporation of the
      cells in the leg vasculature. CONCLUSIONS: Our data indicate the presence of a
      cell population within the SVF of human AT characterized as CD34+/CD31-
      exhibiting characteristics of endothelial progenitor cells. Therefore, human AT
      might represent a source of stem/progenitor cells useful for cell therapy to
      improve vasculogenesis in adults.

PMID- 15238462
TI  - Celecoxib, a cyclooxygenase-2 inhibitor, reduces neointimal hyperplasia through
      inhibition of Akt signaling.
AB  - BACKGROUND: Celecoxib has been shown to have antitumor effects that may be
      mediated through the cyclooxygenase-independent inhibition of Akt signaling.
      Here, we examined the effects of celecoxib on neointimal formation after balloon
      injury and its mechanism of action. METHODS AND RESULTS: In vitro experiments
      were performed to evaluate the effects of celecoxib on the Akt/GSK signaling axis
      and the viability of rat vascular smooth muscle cells (VSMCs). In vivo
      experiments examined the effects of celecoxib, aspirin, and vehicle on neointimal
      growth after denudation injury to rat carotid arteries. In vitro, celecoxib
      suppressed the phosphorylation of Akt and GSK in cultured VSMCs, leading to a
      reduction in viable cell number, which was reversed by transduction of
      constitutively active Akt. Such a reduction in cell number was mediated by
      inhibition of proliferation and induction of apoptosis. In vivo, celecoxib
      reduced injury-induced phosphorylation of Akt and GSK, reduced VSMC
      proliferation, and increased caspase-3 activation and VSMC apoptosis at 3 days
      after injury, whereas aspirin had no effect. At 2 weeks after injury, celecoxib
      reduced intima-to-media ratio, whereas aspirin had no effect. Adenovirus-mediated
      delivery of dominant negative Akt was as effective as celecoxib at inhibiting
      neointimal formation. Conversely, gene delivery of constitutively active Akt
      significantly reversed the inhibition of intimal hyperplasia by celecoxib,
      providing causal evidence that the modulation of Akt signaling by celecoxib is a
      physiologically relevant mechanism. CONCLUSIONS: Celecoxib is a potential
      inhibitor of neointimal formation by blocking injury-induced Akt activation.
      These findings suggest a potential use for celecoxib in the prevention of
      restenosis after angioplasty.

PMID- 15238465
TI  - Widespread targets for friendly fire in acute coronary syndromes.

PMID- 15238466
TI  - Protein kinase Cbeta isoform inhibitors: a new treatment for diabetic
      cardiovascular diseases.

PMID- 15238467
TI  - Approach to "aspirin allergy" in cardiovascular patients.

PMID- 15238468
TI  - Images in cardiovascular medicine. Vascular healing 4 years after the
      implantation of sirolimus-eluting stent in humans: a histopathological
      examination.

PMID- 15238469
TI  - First, the bad news...

PMID- 15238470
TI  - Mesothelioma and venous thrombosis.

PMID- 15238471
TI  - Mesothelioma and venous thrombosis.

PMID- 15238473
TI  - Kickbacks and self-referral.

PMID- 15238474
TI  - Kickbacks and self-referral.

PMID- 15238475
TI  - Elective cesarean section.

PMID- 15238476
TI  - Elective cesarean section.

PMID- 15238477
TI  - Elective cesarean section.

PMID- 15238478
TI  - Elective cesarean section.

PMID- 15238480
TI  - Elective cesarean section.

PMID- 15238482
TI  - Global diet and exercise plan approved.

PMID- 15238481
TI  - Hospitals battling outbreaks of C. difficile.

PMID- 15238483
TI  - Need for national surveillance for hospital infections.

PMID- 15238484
TI  - UK bans, Health Canada warns about antidepressants.

PMID- 15238485
TI  - Legal action against GSK over SSRI data.

PMID- 15238486
TI  - Stockholders protest Pfizer's drug prices.

PMID- 15238487
TI  - Number of living organ donors doubled in 7 years.

PMID- 15238488
TI  - Manitoba refuses to fund abortions at clinic.

PMID- 15238489
TI  - UK MDs oppose selling statins without prescription.

PMID- 15238490
TI  - Clostridium difficile infection in hospitals: a brewing storm.

PMID- 15238491
TI  - Does tighter perioperative glycemic control improve outcomes for diabetic
      patients undergoing coronary artery bypass graft surgery?

PMID- 15238492
TI  - Erythematous groin plaque in a patient with multiple myeloma.

PMID- 15238493
TI  - Risk of Clostridium difficile diarrhea among hospital inpatients prescribed
      proton pump inhibitors: cohort and case-control studies.
AB  - BACKGROUND: Antibiotic disruption of the normal intestinal flora is a well-known
      risk factor for Clostridium difficile-associated diarrhea. Reduced gastric
      acidity has been suggested as a risk factor, and we hypothesized that proton pump
      inhibitors, because of their potency, may be an independent risk factor for this
      problem. METHODS: For the cohort study we identified from a pharmacy database
      1187 inpatients at a Montreal teaching hospital who received antibiotics over a 9
      month period beginning in August 2002. We compared patients in this group who had
      also received a proton pump inhibitor or an H(2) blocker with patients who had
      not received acid suppressive therapy. Hospital laboratory reports of positive
      assay results for C. difficile toxin were used to ascertain cases in the cohort.
      To assess the possibility that proton pump inhibitors were prescribed to patients
      who were sicker and had other risk factors for C. difficile infection, we did a
      case-control study at a second Montreal teaching hospital. Cases were defined as
      patients who were positive for C. difficile toxin and who had a history of
      diarrhea (n = 94). Control subjects were selected from among patients who had
      received an antibiotic and were matched to cases by ward, age within 5 years and
      class of antibiotics (n = 94). RESULTS: In the cohort study, C. difficile
      diarrhea developed in 81 (6.8%) of the 1187 patients who received antibiotics
      while in hospital. In a multivariate analysis, C. difficile diarrhea was
      significantly associated with use of proton pump inhibitors (adjusted odds ratio
      [OR] 2.1, 95% confidence interval [CI] 1.2- 3.5), receipt of 3 or more
      antibiotics (OR 2.1, 95% CI 1.3- 3.4) and admission to a medical ward (OR 4.1,
      95% CI 2.3- 7.3). In the case-control study C. difficile diarrhea was associated
      with female sex (adjusted OR 2.1, 95% CI 1.1-4.0), prior renal failure (adjusted
      OR 4.3, 95% CI 1.5-11.9), hospital admission in the 3 months before the index
      admission (adjusted OR 2.6, 95% CI 1.4-5.2) and use of proton pump inhibitors
      (adjusted OR 2.7, 95% CI 1.4-5.2). INTERPRETATION: Patients in hospital who
      received proton pump inhibitors were at increased risk of C. difficile diarrhea.

PMID- 15238494
TI  - Lack of insurance coverage for testing supplies is associated with poorer
      glycemic control in patients with type 2 diabetes.
AB  - BACKGROUND: Public insurance for testing supplies for self-monitoring of blood
      glucose is highly variable across Canada. We sought to determine if insured
      patients were more likely than uninsured patients to use self-monitoring and
      whether they had better glycemic control. METHODS: We used baseline survey and
      laboratory data from patients enrolled in a randomized controlled trial examining
      the effect of paying for testing supplies on glycemic control. We recruited
      patients through community pharmacies in Alberta and Saskatchewan from Nov. 2001
      to June 2003. To avoid concerns regarding differences in provincial coverage of
      self-monitoring and medications, we report the analysis of Alberta patients only.
      RESULTS: Among our sample of 405 patients, 41% had private or public insurance
      coverage for self-monitoring testing supplies. Patients with insurance had
      significantly lower hemoglobin A(1c) concentrations than those without insurance
      coverage (7.1% v. 7.4%, p = 0.03). Patients with insurance were younger, had a
      higher income, were less likely to have a high school education and were less
      likely to be married or living with a partner. In multivariate analyses that
      controlled for these and other potential confounders, lack of insurance coverage
      for self-monitoring testing supplies was still significantly associated with
      higher hemoglobin A(1c) concentrations (adjusted difference 0.5%, p = 0.006).
      INTERPRETATION: Patients without insurance for self-monitoring test strips had
      poorer glycemic control.

PMID- 15238495
TI  - Clostridium difficile infection in hospitals: risk factors and responses.

PMID- 15238496
TI  - Clostridium difficile: a formidable foe.

PMID- 15238497
TI  - Glycemic self-monitoring and insurance coverage.

PMID- 15238501
TI  - Re: baroreceptors and the long-term control of blood pressure.

PMID- 15238504
TI  - Strain-specific variants of the mouse Cftr promoter region reveal transcriptional
      regulatory elements.
AB  - Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA
      levels is not well understood. Mouse Cftr mRNA shows strain-dependent expression
      differences that cannot be fully explained by variation at non-Cftr loci.
      Differences in tracheal and colonic expression appear to be due predominantly to
      elements linked to Cftr. Fifteen single nucleotide sequence variations were found
      within 1.4 kb 5' to the translation start site between the inbred lines A/J,
      C57BL/6J and 129/SvJ. In addition, 129/SvJ carries a 100 bp deletion relative to
      the other two strains. These variants were investigated by sequentially deleting
      5' regions and measuring luciferase reporter activity from transfected, mouse
      epithelial cell lines derived from pancreatic duct, renal collecting duct,
      salivary gland and trachea. These assays identified a region between -524 and 
      834 in the C57BL/6J promoter, but not in A/J or 129/SvJ, capable of repressing
      expression. Sequence analysis and gel mobility shift assays suggest that the
      transcription factor MZF is involved in the strain-dependent effect. It was also
      apparent that several reporter constructs displayed expression differences
      between cell lines, possibly indicating the presence of tissue-specific elements.

PMID- 15238498
TI  - Clostridium difficile-associated diarrhea in adults.
AB  - Clostridium difficile is the most important cause of nosocomial diarrhea in
      adults. Illness may range from mild watery diarrhea to life-threatening colitis.
      An antecedent disruption of the normal colonic flora followed by exposure to a
      toxigenic strain of C. difficile are necessary first steps in the pathogenesis of
      disease. Diagnosis is based primarily on the detection of C. difficile toxin A or
      toxin B. First-line treatment is with oral metronidazole therapy. Treatment with
      oral vancomycin therapy should be reserved for patients who have
      contraindications or intolerance to metronidazole or who fail to respond to first
      line therapy.

PMID- 15238505
TI  - Affected sib-pair analysis of the contribution of HLA class I and class II loci
      to development of cervical cancer.
AB  - Cervical cancer is a multifactorial disease and infection by oncogenic human
      papilloma viruses represents the main environmental risk factor. Only a subset of
      infections becomes persistent and develops into cancer, implying that genetic
      susceptibility factors are needed for malignant progression. Here, we use a
      population-based cohort of affected sib-pairs (ASPs) to examine the role of the
      human leukocyte antigen (HLA) class I and class II loci in cervical cancer
      susceptibility. Analysis of 278 ASPs revealed significant excess genetic sharing
      for all three HLA class II loci studied, DPB1, DQB1 and DRB1, with the strongest
      evidence for DQB1 and DRB1. No evidence of excess sharing was observed for the
      HLA class I HLA-B and HLA-A loci. When the material was stratified on the basis
      of the DQB1*0602/DRB1*1501 susceptibility haplotype, carriers showed significant
      sharing for all loci, whereas non-carriers showed no evidence of excess genetic
      sharing at any of the loci. However, for the DPB1 locus there was no difference
      in allele frequency between carriers and non-carriers indicating that the effect
      seen in DPB1 is not simply due to linkage disequilibrium. Our results show that
      the HLA class II represents a major genetic susceptibility locus to cervical
      cancer in contrary to the class I that do not appear to have a significant impact
      on predisposition to the disease. The strongest class II effects are coming from
      the DQB1 and DRB1 loci, but the DPB1 locus also contributes to the susceptibility
      to cervical cancer.

PMID- 15238506
TI  - Enhancing linkage analysis of complex disorders: an evaluation of high-density
      genotyping.
AB  - To explore the potential value of recently developed high-density linkage mapping
      methods in the analysis of complex disease we have regenotyped five nuclear
      families first studied in the 1996 UK multiple sclerosis linkage genome screen,
      using Applied Biosystems high-density microsatellite linkage mapping set, the
      Illumina BeadArray linkage mapping panel (version 3) and the Affymetrix GeneChip
      Human Mapping 10K array. We found that genotyping success, information extraction
      and genotyping accuracy were improved with all systems. These improvements were
      particularly marked with the SNP-based methods (Illumina and Affymetrix), with
      little difference between these. The extent of additional information extracted
      is considerable, indicating that reanalysis of existing multiplex families using
      these newer systems would substantially increase power.

PMID- 15238507
TI  - Effects on fear reactivity in XO mice are due to haploinsufficiency of a non-PAR
      X gene: implications for emotional function in Turner's syndrome.
AB  - Recent work has indicated altered emotional functioning in Turner's syndrome (TS)
      subjects (45,XO). We examined the role of X-chromosome deficiency on fear
      reactivity in X-monosomic mice (39,XO), and found that they exhibited anxiogenic
      behaviour relative to normal females (40,XX). A molecular candidate for this
      effect is Steroid sulfatase (Sts) as this is located in the pseudoautosomal
      region (PAR) of the X-chromosome and consequently is normally biallelically
      expressed. In addition, the steroid sulfatase enzyme (STS) is putatively linked
      to fear reactivity by an effect on GABAA receptors via the action of
      neurosteroids. Real-time PCR demonstrated that levels of Sts mRNA were reduced by
      half in the brains of 39,XO mice compared with 40,XX, and that expression levels
      of a number of GABAA subunits previously shown to be important components of fear
      processing (Gabra3, Gabra1 and Gabrg2) were also altered. However, 40,XY*X mice,
      in which the Y*X is a small chromosome comprising of a complete PAR and a small
      non-PAR segment of the X-chromosome, exhibited the same pattern of fear
      reactivity behaviour as 39,XO animals, but equivalent expression levels of Sts,
      Gabra1, Gabra3 and Gabrg2 to 40,XX females. This showed that although Sts may
      cause alterations in GABAA subunit expression, these changes do not result in
      increased fear reactivity. This suggests an alternative X-chromosome gene, that
      escapes inactivation, is responsible for the differences in fear reactivity
      between 39,XO and 40,XX mice. These findings inform the TS data, and point to
      novel genetic mechanisms that may be of general significance to the neurobiology
      of fear.

PMID- 15238508
TI  - Defects in neuromuscular junction structure in dystrophic muscle are corrected by
      expression of a NOS transgene in dystrophin-deficient muscles, but not in muscles
      lacking alpha- and beta1-syntrophins.
AB  - Muscular dystrophies that arise from mutations of genes that encode proteins in
      the dystrophin-glycoprotein complex (DGC) frequently involve defects in the
      structure of neuromuscular junctions (NMJs). DGC mutations that cause NMJ defects
      typically cause a secondary loss of neuronal nitric oxide synthase (nNOS) from
      the post-synaptic membrane. We tested the hypothesis that reduction of muscle
      derived NO production causes NMJ defects in DGC mutants by analyzing the effect
      of modulating muscle NO production on NMJ structure in mutant and wild-type
      muscles. We found that nNOS null mutants, dystrophin-deficient mdx mice and alpha
      syntrophin null mutants showed reductions in the concentration of acetylcholine
      receptors (AChRs) at the post-synaptic membrane. Also, expression of a muscle
      specific NOS transgene increased AChR concentration, which reflected an increase
      in both AChR expression and clustering. NOS transgene expression also increased
      the size of NMJs, and partially corrected defects in normal NMJ architecture that
      were observed in mdx and alpha-syntrophin null muscles. In addition, stimulation
      of AChR clustering in vitro by application of laminin or VVA B4 lectin induced a
      3-4-fold increase in NOS activity and increased AChR clustering that could be
      prevented by NOS inhibition. However, the partial rescue of NMJ structure by
      expression of a NOS transgene required the expression of alpha- or beta1
      syntrophin at the NMJ; partial NMJ rescue was seen in the muscles of alpha
      syntrophin mutants that expressed beta1-syntrophin, but no rescue was observed in
      muscles of alpha-syntrophin mutants that also lacked beta1-syntrophin. These
      findings show that NO promotes AChR expression and clustering in vivo and
      contributes to normal NMJ architecture. The results suggest that defects in NMJ
      structure that occur in some DGC mutants can result from the secondary loss of
      NOS from muscle.

PMID- 15238509
TI  - Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope
      disease?
AB  - Facioscapulohumeral muscular dystrophy (FSHD) may be a new member of the class of
      neuromuscular diseases (NMD) due to defects in the nuclear envelope. Unlike other
      NMDs with primary defects in nuclear envelope proteins, however, FSHD may result
      from inappropriate chromatin interactions at the envelope. 3D Immuno-FISH and a
      novel method of 3D by 2D analysis using NucProfile were developed to examine
      nuclear organization of the FSHD genomic region. In contrast to most other
      telomeres, the FSHD region at 4q35.2 localizes to the nuclear periphery. This
      localization is consistent in normal myoblasts, myotubes, fibroblasts and
      lymphoblasts, does not vary significantly throughout the cell cycle, and is
      independent of chromosome territory effects. The nuclear lamina protein lamin A/C
      is required for FSHD region chromatin localization to the nuclear envelope, as
      the association is lost in lamin A/C null fibroblasts. As both normal and
      affected alleles (deleted for the subtelomeric repeat D4Z4) localize to the
      nuclear periphery, FSHD likely arises instead from improper interactions with
      transcription factors or chromatin modifiers at the nuclear envelope.
      Interestingly, it is not D4Z4 itself that mediates interaction with the envelope,
      as sequences proximal to D4Z4 (i.e. D4S139) localize closer to the nuclear
      periphery, perhaps accounting for the chromosome 4 specificity of the disease.

PMID- 15238510
TI  - Leo Szilard: a personal remembrance.

PMID- 15238511
TI  - Epistasis and its relationship to canalization in the RNA virus phi 6.
AB  - Although deleterious mutations are believed to play a critical role in evolution,
      assessing their realized effect has been difficult. A key parameter governing the
      effect of deleterious mutations is the nature of epistasis, the interaction
      between the mutations. RNA viruses should provide one of the best systems for
      investigating the nature of epistasis because the high mutation rate allows a
      thorough investigation of mutational effects and interactions. Nonetheless,
      previous investigations of RNA viruses by S. Crotty and co-workers and by S. F.
      Elena have been unable to detect a significant effect of epistasis. Here we
      provide evidence that positive epistasis is characteristic of deleterious
      mutations in the RNA bacteriophage phi 6. We estimated the effects of deleterious
      mutations by performing mutation-accumulation experiments on five viral genotypes
      of decreasing fitness. We inferred positive epistasis because viral genotypes
      with low fitness were found to be less sensitive to deleterious mutations. We
      further examined environmental sensitivity in these genotypes and found that low
      fitness genotypes were also less sensitive to environmental perturbations. Our
      results suggest that even random mutations impact the degree of canalization, the
      buffering of a phenotype against genetic and environmental perturbations. In
      addition, our results suggest that genetic and environmental canalization have
      the same developmental basis and finally that an understanding of the nature of
      epistasis may first require an understanding of the nature of canalization.

PMID- 15238512
TI  - A dnaT mutant with phenotypes similar to those of a priA2::kan mutant in
      Escherichia coli K-12.
AB  - The ability to repair damaged replication forks and restart them is important for
      cell survival. DnaT is essential for replication restart in vitro and yet no
      definite genetic analysis has been done in Escherichia coli K-12. To begin,
      dnaT822, an in-frame six-codon (87-92) deletion was constructed. DnaT822 mutants
      show colony size, cell morphology, inability to properly partition nucleoids, UV
      sensitivity, and basal SOS expression similar to priA2::kan mutants. DnaT822
      priA2::kan double mutants had phenotypes similar to those of the single mutants.
      DnaT822 and dnaT822 priA2::kan mutant phenotypes were fully suppressed by
      dnaC809. Previously, a dominant temperature-sensitive lethal mutation, dnaT1, had
      been isolated in E. coli 15T(-). DnaT1 was found to have a base-pair change
      relative to the E. coli 15T(-) and E. coli K-12 dnaT genes that led to a single
      amino acid change: R152C. A plasmid-encoded E. coli K-12 mutant dnaT gene with
      the R152C amino acid substitution did not display a dominant temperature
      sensitive lethal phenotype in a dnaT(+) strain of E. coli K-12. Instead, this
      mutant dnaT gene was found to complement the E. coli K-12 dnaT822 mutant
      phenotypes. The significance of these results is discussed in terms of models for
      replication restart.

PMID- 15238513
TI  - The origin recognition complex links replication, sister chromatid cohesion and
      transcriptional silencing in Saccharomyces cerevisiae.
AB  - Mutations in genes encoding the origin recognition complex (ORC) of Saccharomyces
      cerevisiae affect initiation of DNA replication and transcriptional repression at
      the silent mating-type loci. To explore the function of ORC in more detail, a
      screen for genetic interactions was undertaken using large-scale synthetic lethal
      analysis. Combination of orc2-1 and orc5-1 alleles with the complete set of
      haploid deletion mutants revealed synthetic lethal/sick phenotypes with genes
      involved in DNA replication, chromatin structure, checkpoints, DNA repair and
      recombination, and other genes that were unexpected on the basis of previous
      studies of ORC. Many of these genetic interactions are shared with other genes
      that are involved in initiation of DNA replication. Strong synthetic interactions
      were demonstrated with null mutations in genes that contribute to sister
      chromatid cohesion. A genetic interaction between orc5-1 and the cohesin mutant
      scc1-73 suggested that ORC function contributes to sister chromatid cohesion.
      Thus, comprehensive screening for genetic interactions with a replication gene
      revealed a connection between initiation of DNA replication and sister chromatid
      cohesion. Further experiments linked sister chromatid cohesion genes to silencing
      at mating-type loci and telomeres.

PMID- 15238514
TI  - Conserved and nonconserved proteins for meiotic DNA breakage and repair in
      yeasts.
AB  - During meiosis DNA double-strand breaks initiate recombination in the distantly
      related budding and fission yeasts and perhaps in most eukaryotes. Repair of
      broken meiotic DNA is essential for formation of viable gametes. We report here
      distinct but overlapping sets of proteins in these yeasts required for formation
      and repair of double-strand breaks. Meiotic DNA breakage in Schizosaccharomyces
      pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are
      required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA
      break repair in both yeasts. DNA breakage required the S. pombe midmeiosis
      transcription factor Mei4, but the structurally unrelated midmeiosis
      transcription factor Ndt80 is not required for breakage in S. cerevisiae. Rhp51,
      Swi5, and Rad22 + Rti1 were required for full levels of DNA repair in S. pombe,
      as are the related S. cerevisiae proteins Rad51, Sae3, and Rad52. Dmc1 was not
      required for repair in S. pombe, but its homolog Dmc1 is required in the well
      studied strain SK1 of S. cerevisiae. Additional proteins required in one yeast
      have no obvious homologs in the other yeast. The occurrence of conserved and
      nonconserved proteins indicates potential diversity in the mechanism of meiotic
      recombination and divergence of the machinery during the evolution of eukaryotes.

PMID- 15238515
TI  - Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular
      function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces
      cerevisiae.
AB  - Adenine nucleotide translocase (Ant) catalyzes ADP/ATP exchange between the
      cytosol and the mitochondrial matrix. It is also proposed to form or regulate the
      mitochondrial permeability transition pore, a megachannel of high conductancy on
      the mitochondrial membranes. Eukaryotic genomes generally contain multiple
      isoforms of Ant. In this study, it is shown that the Ant isoforms are
      functionally differentiated in Saccharomyces cerevisiae. Although the three yeast
      Ant proteins can equally support respiration (the R function), Aac2p and Aac3p,
      but not Aac1p, have an additional physiological function essential for cell
      viability (the V function). The loss of V function in aac2 mutants leads to a
      lethal phenotype under both aerobic and anaerobic conditions. The lethality is
      suppressed by a strain-polymorphic locus, named SAL1 (for Suppressor of aac2
      lethality). SAL1 was identified to encode an evolutionarily conserved protein of
      the mitochondrial carrier family. Notably, the Sal1 protein was shown to bind
      calcium through two EF-hand motifs located on its amino terminus. Calcium binding
      is essential for the suppressor activity. Finally, Sal1p is not required for
      oxidative phosphorylation and its overexpression does not complement the R(-)
      phenotype of aac2 mutants. On the basis of these observations, it is proposed
      that Aac2p and Sal1p may define two parallel pathways that transport a nucleotide
      substrate in an operational mode distinct from ADP/ATP exchange.

PMID- 15238516
TI  - A genetic linkage map of Cryptococcus neoformans variety neoformans serotype D
      (Filobasidiella neoformans).
AB  - To construct a genetic linkage map of the heterothallic yeast, Cryptococcus
      neoformans (Filobasidiella neoformans), we crossed two mating-compatible strains
      and analyzed 94 progeny for the segregation of 301 polymorphic markers,
      consisting of 228 restriction site polymorphisms, 63 microsatellites, two indels,
      and eight mating-type (MAT)-associated markers. All but six markers showed no
      significant (P < 0.05) segregation distortion. At a minimum LOD score of 6.0 and
      a maximum recombination frequency of 0.30, 20 linkage groups were resolved,
      resulting in a map length of approximately 1500 cM. Average marker density is 5.4
      cM (range 1-28.7 cM). Hybridization of selected markers to blots of
      electrophoretic karyotypes unambiguously assigned all linkage groups to
      chromosomes and led us to conclude that the C. neoformans genome is approximately
      20.2 Mb, comprising 14 chromosomes ranging in size from 0.8 to 2.3 Mb, with a
      ratio of approximately 13.2 kb/cM averaged across the genome. However, only 2 of
      12 ungrouped markers hybridized to chromosome 10. The hybridizations revealed at
      least one possible reciprocal translocation involving chromosomes 8, 9, and 12.
      This map has been critical to genome sequence assembly and will be essential for
      future studies of quantitative trait inheritance.

PMID- 15238517
TI  - The GAR-3 muscarinic receptor cooperates with calcium signals to regulate muscle
      contraction in the Caenorhabditis elegans pharynx.
AB  - Muscarinic acetylcholine receptors regulate the activity of neurons and muscle
      cells through G-protein-coupled cascades. Here, we identify a pathway through
      which the GAR-3 muscarinic receptor regulates both membrane potential and
      excitation-contraction coupling in the Caenorhabditis elegans pharyngeal muscle.
      GAR-3 signaling is enhanced in worms overexpressing gar-3 or lacking GPB-2, a G
      protein beta-subunit involved in RGS-mediated inhibition of G(o)alpha- and
      G(q)alpha-linked pathways. High levels of signaling through GAR-3 inhibit
      pharyngeal muscle relaxation and impair feeding--but do not block muscle
      repolarization--when worms are exposed to arecoline, a muscarinic agonist. Loss
      of gar-3 function results in shortened action potentials and brief muscle
      contractions in the pharyngeal terminal bulb. High levels of calcium entry
      through voltage-gated channels also impair terminal bulb relaxation and sensitize
      worms to the toxic effects of arecoline. Mutation of gar-3 reverses this
      sensitivity, suggesting that GAR-3 regulates calcium influx or calcium-dependent
      processes. Because the effects of GAR-3 signaling on membrane depolarization and
      muscle contraction can be separated, we conclude that GAR-3 regulates multiple
      calcium-dependent processes in the C. elegans pharyngeal muscle.

PMID- 15238518
TI  - The PGL family proteins associate with germ granules and function redundantly in
      Caenorhabditis elegans germline development.
AB  - PGL-1 is a constitutive protein component of C. elegans germ granules, also known
      as P granules. Maternally supplied PGL-1 is essential for germline development
      but only at elevated temperature, raising the possibility that redundant factors
      provide sufficient function at lower temperatures. We have identified two PGL-1
      related proteins, PGL-2 and PGL-3, by sequence analysis of the C. elegans genome
      and by a yeast two-hybrid screen for proteins that interact with PGL-1. PGL-3 is
      associated with P granules at all stages of development, while PGL-2 is
      associated with P granules only during postembryonic development. All three PGL
      proteins interact with each other in vitro. Furthermore, PGL-1 and PGL-3 are co
      immunoprecipitated from embryo extracts, indicating that they are indeed in the
      same protein complex in vivo. Nevertheless, each PGL protein localizes to P
      granules independently of the other two. pgl-2 or pgl-3 single-mutant worms do
      not show obvious defects in germline development. However, pgl-1; pgl-3 (but not
      pgl-2; pgl-1) double-mutant hermaphrodites and males show significantly enhanced
      sterility at all temperatures, compared to pgl-1 alone. Mutant hermaphrodites
      show defects in germline proliferation and in production of healthy gametes and
      viable embryos. Our findings demonstrate that both PGL-2 and PGL-3 are components
      of P granules, both interact with PGL-1, and at least PGL-3 functions redundantly
      with PGL-1 to ensure fertility in both sexes of C. elegans.

PMID- 15238519
TI  - Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva genes
      negatively regulate the anaphase-promoting complex gene mat-3/APC8.
AB  - Retinoblastoma (Rb)/E2F complexes repress expression of many genes important for
      G(1)-to-S transition, but also appear to regulate gene expression at other stages
      of the cell cycle. In C. elegans, lin-35/Rb and other synthetic Multivulva
      (SynMuv) group B genes function redundantly with other sets of genes to regulate
      G(1)/S progression, vulval and pharyngeal differentiation, and other unknown
      processes required for viability. Here we show that lin-35/Rb, efl-1/E2F, and
      other SynMuv B genes negatively regulate a component of the anaphase-promoting
      complex or cyclosome (APC/C). The APC/C is a multisubunit complex that promotes
      metaphase-to-anaphase progression and G(1) arrest by targeting different
      substrates for ubiquitination and proteasome-mediated destruction. The C. elegans
      APC/C gene mat-3/APC8 has been defined by temperature-sensitive embryonic lethal
      alleles that strongly affect germline meiosis and mitosis but only weakly affect
      somatic development. We describe severe nonconditional mat-3 alleles and a
      hypomorphic viable allele (ku233), all of which affect postembryonic cell
      divisions including those of the vulval lineage. The ku233 lesion is located
      outside of the mat-3 coding region and reduces mat-3 mRNA expression. Loss-of
      function alleles of lin-35/Rb and other SynMuv B genes suppress mat-3(ku233)
      defects by restoring mat-3 mRNA to wild-type levels. Therefore, Rb/E2F complexes
      appear to repress mat-3 expression.

PMID- 15238520
TI  - The Caenorhabditis elegans pvl-5 gene protects hypodermal cells from ced-3
      dependent, ced-4-independent cell death.
AB  - Programmed cell death (PCD) is regulated by multiple evolutionarily conserved
      mechanisms to ensure the survival of the cell. Here we describe pvl-5, a gene
      that likely regulates PCD in Caenorhabditis elegans. In wild-type hermaphrodites
      at the L2 stage there are 11 Pn.p hypodermal cells in the ventral midline arrayed
      along the anterior-posterior axis and 6 of these cells become the vulval
      precursor cells. In pvl-5(ga87) animals there are fewer Pn.p cells (average of
      7.0) present at this time. Lineage analysis reveals that the missing Pn.p cells
      die around the time of the L1 molt in a manner that often resembles the
      programmed cell deaths that occur normally in C. elegans development. This Pn.p
      cell death is suppressed by mutations in the caspase gene ced-3 and in the bcl-2
      homolog ced-9, suggesting that the Pn.p cells are dying by PCD in pvl-5 mutants.
      Surprisingly, the Pn.p cell death is not suppressed by loss of ced-4 function.
      ced-4 (Apaf-1) is required for all previously known apoptotic cell deaths in C.
      elegans. This suggests that loss of pvl-5 function leads to the activation of a
      ced-3-dependent, ced-4-independent form of PCD and that pvl-5 may normally
      function to protect cells from inappropriate activation of the apoptotic pathway.

PMID- 15238521
TI  - Regulation of the Drosophila epidermal growth factor-ligand vein is mediated by
      multiple domains.
AB  - Vein (Vn), a ligand for the Drosophila epidermal growth factor receptor (Egfr),
      has a complex structure including a PEST, Ig, and EGF domain. We analyzed the
      structure-function relationships of Vn by assaying deletion mutants. The results
      show that each conserved domain influences Vn activity. A PEST deletion increases
      Vn potency and genetic evidence suggests that Vn is regulated by proteasomal
      degradation. The Ig deletion causes toxic effects not seen following expression
      of native Vn, but the Ig domain is not required for Vn localization or for the
      activation of Egfr signaling in wing vein patterning. Remarkably, when the EGF
      domain is deleted, Vn functions as a dominant negative ligand, implying that Vn
      normally physically interacts with another factor to promote its activity. We
      identified additional highly conserved sequences and found several regions that
      affect Vn potency and one that may mediate the effect of dominant negative Vn
      molecules. Together the results show that the activity of Vn is controlled both
      positively and negatively, demonstrating the existence of additional levels at
      which Egfr signaling can be regulated.

PMID- 15238522
TI  - Evidence for multiple cycles of strand invasion during repair of double-strand
      gaps in Drosophila.
AB  - DNA double-strand breaks (DSBs), a major source of genome instability, are often
      repaired through homologous recombination pathways. Models for these pathways
      have been proposed, but the precise mechanisms and the rules governing their use
      remain unclear. In Drosophila, the synthesis-dependent strand annealing (SDSA)
      model can explain most DSB repair. To investigate SDSA, we induced DSBs by
      excision of a P element from the male X chromosome, which produces a 14-kb gap
      relative to the sister chromatid. In wild-type males, repair synthesis tracts are
      usually long, resulting in frequent restoration of the P element. However, repair
      synthesis is often incomplete, resulting in internally deleted P elements. We
      examined the effects of mutations in spn-A, which encodes the Drosophila Rad51
      ortholog. As expected, there is little or no repair synthesis in homozygous spn-A
      mutants after P excision. However, heterozygosity for spn-A mutations also
      resulted in dramatic reductions in the lengths of repair synthesis tracts. These
      findings support a model in which repair DNA synthesis is not highly processive.
      We discuss a model wherein repair of a double-strand gap requires multiple cycles
      of strand invasion, synthesis, and dissociation of the nascent strand. After
      dissociation, the nascent strand may anneal to a complementary single strand,
      reinvade a template to be extended by additional synthesis, or undergo end
      joining. This model can explain aborted SDSA repair events and the prevalence of
      internally deleted transposable elements in genomes.

PMID- 15238523
TI  - A misexpression screen reveals effects of bag-of-marbles and TGF beta class
      signaling on the Drosophila male germ-line stem cell lineage.
AB  - Male gametes are produced throughout reproductive life by a classic stem cell
      mechanism. However, little is known about the molecular mechanisms for lineage
      production that maintain male germ-line stem cell (GSC) populations, regulate
      mitotic amplification divisions, and ensure germ cell differentiation. Here we
      utilize the Drosophila system to identify genes that cause defects in the male
      GSC lineage when forcibly expressed. We conducted a gain-of-function screen using
      a collection of 2050 EP lines and found 55 EP lines that caused defects at early
      stages of spermatogenesis upon forced expression either in germ cells or in
      surrounding somatic support cells. Most strikingly, our analysis of forced
      expression indicated that repression of bag-of-marbles (bam) expression in male
      GSC is important for male GSC survival, while activity of the TGF beta signal
      transduction pathway may play a permissive role in maintenance of GSCs in
      Drosophila testes. In addition, forced activation of the TGF beta signal
      transduction pathway in germ cells inhibits the transition from the
      spermatogonial mitotic amplification program to spermatocyte differentiation.

PMID- 15238524
TI  - Molecular population genetics of male accessory gland proteins in the Drosophila
      simulans complex.
AB  - Accessory gland proteins are a major component of Drosophila seminal fluid. These
      proteins have a variety of functions and may be subject to sexual selection
      and/or antagonistic evolution between the sexes. Most population genetic data
      from these proteins are from D. melanogaster and D. simulans. Here, we extend the
      population genetic analysis of Acp genes to the other simulans complex species,
      D. mauritiana and D. sechellia. We sequenced population samples of seven Acp's
      from D. mauritiana, D. sechellia, and D. simulans. We investigated the population
      genetics of these genes on individual simulans complex lineages and compared Acp
      polymorphism and divergence to polymorphism and divergence from a set of non-Acp
      loci in the same species. Polymorphism and divergence data from the simulans
      complex revealed little evidence for adaptive protein evolution at individual
      loci. However, we observed a dramatically inflated index of dispersion for amino
      acid substitutions in the simulans complex at Acp genes, but not at non-Acp
      genes. This pattern of episodic bursts of protein evolution in Acp's provides the
      strongest evidence to date that the population genetic mechanisms driving Acp
      divergence are different from the mechanisms driving evolution at most Drosophila
      genes.

PMID- 15238525
TI  - Efficient transformation of the beetle Tribolium castaneum using the Minos
      transposable element: quantitative and qualitative analysis of genomic
      integration events.
AB  - Genetic transformation in insects holds great promise as a tool for genetic
      manipulation in species of particular scientific, economic, or medical interest.
      A number of transposable elements have been tested recently as potential vectors
      for transformation in a range of insects. Minos is one of the most promising
      elements because it appears to be active in diverse species and has the capacity
      to carry large inserts. We report here the use of the Minos element as a
      transformation vector in the red flour beetle Tribolium castaneum (Coleoptera),
      an important species for comparative developmental and pest management studies.
      Transgenic G(1) beetles were recovered from 32.4% of fertile G(0)'s injected with
      a plasmid carrying a 3xP3-EGFP-marked transposon and in vitro synthesized mRNA
      encoding the Minos transposase. This transformation efficiency is 2.8-fold higher
      than that observed when using a plasmid helper. Molecular and genetic analyses
      show that several independent insertions can be recovered from a single injected
      parent, but that the majority of transformed individuals carry single Minos
      insertions. These results establish Minos as one of the most efficient vectors
      for genetic transformation in insects. In combination with piggyBac-based
      transgenesis, our work allows the introduction of sophisticated multicomponent
      genetic tools in Tribolium.

PMID- 15238526
TI  - Multilocus methods for estimating population sizes, migration rates and
      divergence time, with applications to the divergence of Drosophila pseudoobscura
      and D. persimilis.
AB  - The genetic study of diverging, closely related populations is required for basic
      questions on demography and speciation, as well as for biodiversity and
      conservation research. However, it is often unclear whether divergence is due
      simply to separation or whether populations have also experienced gene flow.
      These questions can be addressed with a full model of population separation with
      gene flow, by applying a Markov chain Monte Carlo method for estimating the
      posterior probability distribution of model parameters. We have generalized this
      method and made it applicable to data from multiple unlinked loci. These loci can
      vary in their modes of inheritance, and inheritance scalars can be implemented
      either as constants or as parameters to be estimated. By treating inheritance
      scalars as parameters it is also possible to address variation among loci in the
      impact via linkage of recurrent selective sweeps or background selection. These
      methods are applied to a large multilocus data set from Drosophila pseudoobscura
      and D. persimilis. The species are estimated to have diverged approximately
      500,000 years ago. Several loci have nonzero estimates of gene flow since the
      initial separation of the species, with considerable variation in gene flow
      estimates among loci, in both directions between the species.

PMID- 15238527
TI  - The BDGP gene disruption project: single transposon insertions associated with
      40% of Drosophila genes.
AB  - The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila
      gene by the insertion of a single transposable element. As part of this effort,
      transposons in >30,000 fly strains were localized and analyzed relative to
      predicted Drosophila gene structures. Approximately 6300 lines that maximize
      genomic coverage were selected to be sent to the Bloomington Stock Center for
      public distribution, bringing the size of the BDGP gene disruption collection to
      7140 lines. It now includes individual lines predicted to disrupt 5362 of the
      13,666 currently annotated Drosophila genes (39%). Other lines contain an
      insertion at least 2 kb from others in the collection and likely mutate
      additional incompletely annotated or uncharacterized genes and chromosomal
      regulatory elements. The remaining strains contain insertions likely to disrupt
      alternative gene promoters or to allow gene misexpression. The expanded BDGP gene
      disruption collection provides a public resource that will facilitate the
      application of Drosophila genetics to diverse biological problems. Finally, the
      project reveals new insight into how transposons interact with a eukaryotic
      genome and helps define optimal strategies for using insertional mutagenesis as a
      genomic tool.

PMID- 15238528
TI  - Drosophila Costal1 mutations are alleles of protein kinase A that modulate
      hedgehog signaling.
AB  - Hedgehog (Hh) signaling is crucial for the development of many tissues, and
      altered Hh signal transduction can result in cancer. The Drosophila Costal1
      (Cos1) and costal2 (cos2) genes have been implicated in Hh signaling. cos2
      encodes a kinesin-related molecule, one component of a cytoplasmic complex of Hh
      signal transducers. Mutations in Cos1 enhance loss-of-function cos2 mutations,
      but the molecular nature of Cos1 has been unknown. We found that previously
      identified alleles of Cos1 actually map to two separate loci. Four alleles of
      Cos1 appear to be dominant-negative mutations of a catalytic subunit of protein
      kinase A (pka-C1) and the fifth allele, Cos1(A1), is a gain-of-function allele of
      the PKA regulatory subunit pka-RII. PKA-RII protein levels are higher in Cos1(A1)
      mutants than in wild type. Overexpression of wild-type pka-RII phenocopies Cos1
      mutants. PKA activity is aberrant in Cos1(A1) mutants. PKA-RII is uniformly
      overproduced in the wing imaginal disc in Cos1(A1) mutants, but only certain
      cells respond by activating the transcription factor Ci and Hh target gene
      transcription. This work shows that overexpression of a wild-type regulatory
      subunit of PKA is sufficient to activate Hh target gene transcription.

PMID- 15238529
TI  - The DrosDel collection: a set of P-element insertions for generating custom
      chromosomal aberrations in Drosophila melanogaster.
AB  - We describe a collection of P-element insertions that have considerable utility
      for generating custom chromosomal aberrations in Drosophila melanogaster. We have
      mobilized a pair of engineered P elements, p[RS3] and p[RS5], to collect 3243
      lines unambiguously mapped to the Drosophila genome sequence. The collection
      contains, on average, an element every 35 kb. We demonstrate the utility of the
      collection for generating custom chromosomal deletions that have their end points
      mapped, with base-pair resolution, to the genome sequence. The collection was
      generated in an isogenic strain, thus affording a uniform background for screens
      where sensitivity to genetic background is high. The entire collection, along
      with a computational and genetic toolbox for designing and generating custom
      deletions, is publicly available. Using the collection it is theoretically
      possible to generate >12,000 deletions between 1 bp and 1 Mb in size by simple
      eye color selection. In addition, a further 37,000 deletions, selectable by
      molecular screening, may be generated. We are now using the collection to
      generate a second-generation deficiency kit that is precisely mapped to the
      genome sequence.

PMID- 15238531
TI  - Natural Wolbachia infections in the Drosophila yakuba species complex do not
      induce cytoplasmic incompatibility but fully rescue the wRi modification.
AB  - In this study, we report data about the presence of Wolbachia in Drosophila
      yakuba, D. teissieri, and D. santomea. Wolbachia strains were characterized using
      their wsp gene sequence and cytoplasmic incompatibility assays. All three species
      were found infected with Wolbachia bacteria closely related to the wAu strain,
      found so far in D. simulans natural populations, and were unable to induce
      cytoplasmic incompatibility. We injected wRi, a CI-inducing strain naturally
      infecting D. simulans, into the three species and the established transinfected
      lines exhibited high levels of CI, suggesting that absence of CI expression is a
      property of the Wolbachia strain naturally present or that CI is specifically
      repressed by the host. We also tested the relationship between the natural
      infection and wRi and found that it fully rescues the wRi modification. This
      result was unexpected, considering the significant evolutionary divergence
      between the two Wolbachia strains.

PMID- 15238530
TI  - Estimates of the genomic mutation rate for detrimental alleles in Drosophila
      melanogaster.
AB  - The net rate of mutation to deleterious but nonlethal alleles and the sizes of
      effects of these mutations are of great significance for many evolutionary
      questions. Here we describe three replicate experiments in which mutations have
      been accumulated on chromosome 3 of Drosophila melanogaster by means of single
      male backcrosses of heterozygotes for a wild-type third chromosome. Egg-to-adult
      viability was assayed for nonlethal homozygous chromosomes. The rates of decline
      in mean and increase in variance (DM and DV, respectively) were estimated. Scaled
      up to the diploid whole genome, the mean DM for homozygous detrimental mutations
      over the three experiments was between 0.8 and 1.8%. The corresponding DV
      estimate was approximately 0.11%. Overall, the results suggest a lower bound
      estimate of at least 12% for the diploid per genome mutation rate for
      detrimentals. The upper bound estimates for the mean selection coefficient were
      between 2 and 10%, depending on the method used. Mutations with selection
      coefficients of at least a few percent must be the major contributors to the
      effects detected here and are likely to be caused mostly by transposable element
      insertions or indels.

PMID- 15238533
TI  - A multistage testing strategy for detection of quantitative trait Loci affecting
      disease resistance in Atlantic salmon.
AB  - A multistage testing strategy to detect QTL for resistance to infectious salmon
      anemia (ISA) in Atlantic salmon is proposed. First, genotyping of amplified
      fragment length polymorphisms (AFLP) and a transmission disequilibrium test (TDT)
      were carried out using dead offspring from a disease resistance challenge test.
      Second, AFLP genotyping among survivors followed by a Mendelian segregation test
      was performed. Third, within-family survival analyses using all offspring were
      developed and applied to significant TDT markers with Mendelian inheritance.
      Maximum-likelihood methodology was developed for TDT with dominant markers to
      exploit linkage disequilibrium within families. The strategy was tested with two
      full-sib families of Atlantic salmon sired by the same male and consisting of 79
      offspring in total. All dead offspring from the two families were typed for 64
      primer combinations, resulting in 340 scored markers. There were 26 significant
      results out of 401 TDTs using dead offspring. In the second stage, only 17 marker
      families showed Mendelian segregation and were tested in survival analysis. A
      permutation test was performed for all survival analyses to compute
      experimentwise P-values. Two markers, aaccac356 and agccta150, were significant
      at P < 0.05 when accounting for multiple testing in the survival analyses. The
      proposed strategy might be more powerful than current mapping strategies because
      it reduces the number of tests to be performed in the last testing stage.

PMID- 15238532
TI  - Evidence that the large noncoding sequence is the main control region of
      maternally and paternally transmitted mitochondrial genomes of the marine mussel
      (Mytilus spp.).
AB  - Both the maternal (F-type) and paternal (M-type) mitochondrial genomes of the
      Mytilus species complex M. edulis/galloprovincialis contain a noncoding sequence
      between the l-rRNA and the tRNA(Tyr) genes, here called the large unassigned
      region (LUR). The LUR, which is shorter in M genomes, is capable of forming
      secondary structures and contains motifs of significant sequence similarity with
      elements known to have specific functions in the sea urchin and the mammalian
      control region. Such features are not present in other noncoding regions of the F
      or M Mytilus mtDNA. The LUR can be divided on the basis of indels and nucleotide
      variation in three domains, which is reminiscent of the tripartite structure of
      the mammalian control region. These features suggest that the LUR is the main
      control region of the Mytilus mitochondrial genome. The middle domain has
      diverged by only 1.5% between F and M genomes, while the average divergence over
      the whole molecule is approximately 20%. In contrast, the first domain is among
      the most divergent parts of the genome. This suggests that different parts of the
      LUR are under different selection constraints that are also different from those
      acting on the coding parts of the molecule.

PMID- 15238534
TI  - A potent modifier of liver cancer risk on distal mouse chromosome 1: linkage
      analysis and characterization of congenic lines.
AB  - The C3H/HeJ (C3H) and CBA/J (CBA) mouse strains are classical mouse models of
      cancer susceptibility, exhibiting high risks for both spontaneous and chemically
      induced liver cancer. By analysis of backcrosses and intercrosses between C3H or
      CBA and resistant B6 mice, we have mapped a potent modifier of hepatocellular
      carcinoma development to distal chromosome 1, linked to the marker D1Mit33 with
      combined LOD(W) scores of approximately 5.9 (C3H) and 6.5 (CBA). We previously
      identified this region as one of two that modify susceptibility in the more
      distantly related C57BR/cdJ (BR) strain. Congenic B6.C3H(D1Mit5-D1Mit17) and
      B6.BR(D1Mit5-D1Mit17) mice developed significantly more liver tumors than B6 mice
      did (6- to 13-fold, P < 10(-11), in males; 3- to 4-fold, P < 10(-3), in females).
      Thus, distal chromosome 1 carries one or more genes that are sufficient to confer
      susceptibility to liver cancer.

PMID- 15238535
TI  - Population genetic and phylogenetic evidence for positive selection on regulatory
      mutations at the factor VII locus in humans.
AB  - The abundance of cis-regulatory polymorphisms in humans suggests that many may
      have been important in human evolution, but evidence for their role is relatively
      rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a
      coagulation factor, have been shown to affect its transcription and protein
      abundance both in vitro and in vivo. Three of these polymorphisms have low
      frequency alleles that decrease expression of F7 and may provide protection
      against myocardial infarction (heart attacks). The fourth polymorphism has a
      minor allele that increases the level of transcription. To look for evidence of
      natural selection on the cis-regulatory variants flanking F7, we genotyped three
      of the polymorphisms in six Old World populations for which we also have data
      from a group of putatively neutral SNPs. Our population genetic analysis shows
      evidence for selection within humans; surprisingly, the strongest evidence is due
      to a large increase in frequency of the high-expression variant in Singaporean
      Chinese. Further characterization of a Japanese population shows that at least
      part of the increase in frequency of the high-expression allele is found in other
      East Asian populations. In addition, to examine interspecific patterns of
      selection we sequenced the homologous 5' noncoding region in chimpanzees,
      bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an
      excess of fixed differences within transcription factor binding sites along the
      human lineage. Our results thus further support the hypothesis that regulatory
      mutations have been important in human evolution.

PMID- 15238537
TI  - Modification of an existing chromosomal inversion to engineer a balancer for
      mouse chromosome 15.
AB  - Chromosomal inversions are valuable genetic tools for mutagenesis screens, where
      appropriately marked inversions can be used as balancer chromosomes to recover
      and maintain mutations in the corresponding chromosomal region. For any inversion
      to be effective as a balancer, it should exhibit both dominant and recessive
      visible traits; ideally the recessive trait should be a fully penetrant lethality
      in which inversion homozygotes die before birth. Unfortunately, most inversions
      recovered by classical radiation or chemical mutagenesis techniques do not have
      an overt phenotype in either the heterozygous or the homozygous state. However,
      they can be modified by relatively simple procedures to make them suitable as an
      appropriately marked balancer. We have used homologous recombination to modify,
      in embryonic stem cells, the recessive-lethal In(15)21Rk inversion to endow it
      with a dominant-visible phenotype. Several ES cell lines were derived from
      inversion heterozygotes, and a keratin-14 (K14) promoter-driven agouti minigene
      was introduced onto the inverted chromosome 15 in the ES cells by gene targeting.
      Mice derived from the targeted ES cells carry the inverted chromosome 15 and, at
      the same time, exhibit lighter coat color on their ears and tails, making this
      modified In(15)21Rk useful as a balancer for proximal mouse chromosome 15.

PMID- 15238536
TI  - Rapid evolution of mammalian X-linked testis-expressed homeobox genes.
AB  - Homeobox genes encode transcription factors that function in various
      developmental processes and are usually evolutionarily conserved in their
      sequences. However, two X-chromosome-linked testis-expressed homeobox genes, one
      from rodents and the other from fruit flies, are known to evolve rapidly under
      positive Darwinian selection. Here we report yet another case, from primates.
      TGIFLX is an X-linked homeobox gene that originated by retroposition of the
      autosomal gene TGIF2, most likely in a common ancestor of rodents and primates.
      While TGIF2 is ubiquitously expressed, TGIFLX is exclusively expressed in adult
      testis. A comparison of the TGIFLX sequences among 16 anthropoid primates
      revealed a significantly higher rate of nonsynonymous nucleotide substitution
      (d(N)) than synonymous substitution (d(S)), strongly suggesting the action of
      positive selection. Although the high d(N)/d(S) ratio is most evident outside the
      homeobox, the homeobox has a d(N)/d(S) of approximately 0.89 and includes two
      codons that are likely under selection. Furthermore, the rate of radical amino
      acid substitutions that alter amino acid charge is significantly greater than
      that of conservative substitutions, suggesting that the selection promotes
      diversity of the protein charge profile. More interestingly, an analysis of 64
      orthologous homeobox genes from humans and mice shows substantially higher rates
      of amino acid substitution in X-linked testis-expressed genes than in other
      genes. These results suggest a general pattern of rapid evolution of mammalian X
      linked testis-expressed homeobox genes. Although the physiological function of
      and the exact selective agent on TGIFLX and other rapidly evolving homeobox genes
      are unclear, the common expression pattern of these transcription factor genes
      led us to conjecture that the selection is related to one or more aspects of male
      reproduction and may contribute to speciation.

PMID- 15238538
TI  - Paternal mitochondrial DNA transmission during nonhuman primate nuclear transfer.
AB  - Offspring produced by nuclear transfer (NT) have identical nuclear DNA (nDNA).
      However, mitochondrial DNA (mtDNA) inheritance could vary considerably. In sheep,
      homoplasmy is maintained since mtDNA is transmitted from the oocyte (recipient)
      only. In contrast, cattle are heteroplasmic, harboring a predominance of
      recipient mtDNA along with varying levels of donor mtDNA. We show that the two
      nonhuman primate Macaca mulatta offspring born by NT have mtDNA from three
      sources: (1) maternal mtDNA from the recipient egg, (2) maternal mtDNA from the
      egg contributing to the donor blastomere, and (3) paternal mtDNA from the sperm
      that fertilized the egg from which the donor blastomere was isolated. The
      introduction of foreign mtDNA into reconstructed recipient eggs has also been
      demonstrated in mice through pronuclear injection and in humans through
      cytoplasmic transfer. The mitochondrial triplasmy following M. mulatta NT
      reported here forces concerns regarding the parental origins of mtDNA in
      clinically reconstructed eggs. In addition, mtDNA heteroplasmy might result in
      the embryonic stem cell lines generated for experimental and therapeutic purposes
      ("therapeutic cloning").

PMID- 15238539
TI  - Light-response quantitative trait loci identified with composite interval and
      eXtreme array mapping in Arabidopsis thaliana.
AB  - Genetic analysis of natural variation in ecotypes of Arabidopsis thaliana can
      facilitate the discovery of new genes or of allelic variants of previously
      identified genes controlling physiological processes in plants. We mapped
      quantitative trait loci (QTL) for light response in recombinant inbred lines
      (RILs) derived from the Columbia and Kashmir accessions via two methods:
      composite interval mapping and eXtreme array mapping (XAM). After measuring
      seedling hypocotyl lengths in blue, red, far-red, and white light, and in
      darkness, eight QTL were identified by composite interval mapping and five
      localized near photoreceptor loci. Two QTL in blue light were associated with
      CRY1 and CRY2, two in red light were near PHYB and PHYC, and one in far-red light
      localized near PHYA. The RED2 and RED5 QTL were verified in segregating lines.
      XAM was tested for the identification of QTL in red light with pools of RILs
      selected for extreme phenotypes. Thousands of single feature polymorphisms
      detected by differential DNA hybridized to high-density oligo-nucleotide arrays
      were used to estimate allele frequency differences between the pools. The RED2
      QTL was identified clearly; differences exceeded a threshold of significance
      determined by simulations. The sensitivities of XAM to population type and size
      and genetic models were also determined by simulation analysis.

PMID- 15238540
TI  - Isolation and gene expression analysis of Arabidopsis thaliana mutants with
      constitutive expression of ATL2, an early elicitor-response RING-H2 zinc-finger
      gene.
AB  - Genes with unstable transcripts often encode proteins that play important
      regulatory roles. ATL2 is a member of a multigene family coding highly related
      RING-H2 zinc-finger proteins that may function as E3 ubiquitin ligases. ATL2 mRNA
      accumulation occurs rapidly and transiently after incubation with elicitors of
      pathogen response. We screened 50,000 M(2) families from a line that carries a
      fusion of pATL2 to the GUS reporter gene and isolated five mutants, which we
      named eca (expresion constitutiva de ATL2), that showed constitutive expression
      of the reporter gene. One mutant exhibits a drastic stunted phenotype while the
      other four grow similarly to wild type. Two early chitin-induced genes and known
      pathogenesis-related genes such as NPR1, PAL, and CHS are activated in all the
      mutants whereas members of the ATL family and PR-1 and PDF2.1, which are markers
      of the salicylic acid (SA) jasmonate (JA) defense-response pathways, display
      differential expression between the mutants. These observations indicate that the
      ECA gene products may function in the early steps of an elicitor-response
      pathway, although some of them may function at other stages on the SA or JA
      defense-response pathways. Likewise, the fact that ATL2 and other members of the
      ATL family are activated in eca mutants links the induction of this putative
      class of ubiquitin ligases to plant defense signaling pathways.

PMID- 15238541
TI  - Evidence for nucleolus organizer regions as the units of regulation in nucleolar
      dominance in Arabidopsis thaliana interecotype hybrids.
AB  - Nucleolar dominance describes the silencing of one parent's ribosomal RNA (rRNA)
      genes in a genetic hybrid. In Arabidopsis thaliana, rRNA genes are clustered in
      two nucleolus organizer regions, NOR2 and NOR4. In F(8) recombinant inbreds (RI)
      of the A. thaliana ecotypes Ler and Cvi, lines that display strong nucleolar
      dominance inherited a specific combination of NORs, Cvi NOR4 and Ler NOR2. These
      lines express almost all rRNA from Cvi NOR4. The reciprocal NOR genotype, Ler
      NOR4/Cvi NOR2, allowed for expression of rRNA genes from both NORs. Collectively,
      these data reveal that neither Cvi rRNA genes nor NOR4 are always dominant.
      Furthermore, strong nucleolar dominance does not occur in every RI line
      inheriting Cvi NOR4 and Ler NOR2, indicating stochastic effects or the
      involvement of other genes segregating in the RI mapping population. A partial
      explanation is provided by an unlinked locus, identified by QTL analysis, that
      displays an epistatic interaction with the NORs and affects the relative
      expression of NOR4 vs. NOR2. Collectively, the data indicate that nucleolar
      dominance is a complex trait in which NORs, rather than individual rRNA genes,
      are the likely units of regulation.

PMID- 15238542
TI  - Sequence polymorphism in polyploid wheat and their d-genome diploid ancestor.
AB  - Sequencing was used to investigate the origin of the D genome of the
      allopolyploid species Triticum aestivum and Aegilops cylindrica. A 247-bp region
      of the wheat D-genome Xwye838 locus, encoding ADP-glucopyrophosphorylase, and a
      326-bp region of the wheat D-genome Gss locus, encoding granule-bound starch
      synthase, were sequenced in a total 564 lines of hexaploid wheat (T. aestivum,
      genome AABBDD) involving all its subspecies and 203 lines of Aegilops tauschii,
      the diploid source of the wheat D genome. In Ae. tauschii, two SNP variants were
      detected at the Xwye838 locus and 11 haplotypes at the Gss locus. Two haplotypes
      with contrasting frequencies were found at each locus in wheat. Both wheat
      Xwye838 variants, but only one of the Gss haplotypes seen in wheat, were found
      among the Ae. tauschii lines. The other wheat Gss haplotype was not found in
      either Ae. tauschii or 70 lines of tetraploid Ae. cylindrica (genomes CCDD),
      which is known to hybridize with wheat. It is concluded that both T. aestivum and
      Ae. cylindrica originated recurrently, with at least two genetically distinct
      progenitors contributing to the formation of the D genome in both species.

PMID- 15238543
TI  - Detecting selection in noncoding regions of nucleotide sequences.
AB  - We present a maximum-likelihood method for examining the selection pressure and
      detecting positive selection in noncoding regions using multiple aligned DNA
      sequences. The rate of substitution in noncoding regions relative to the rate of
      synonymous substitution in coding regions is modeled by a parameter zeta. When a
      site in a noncoding region is evolving neutrally zeta = 1, while zeta > 1
      indicates the action of positive selection, and zeta < 1 suggests negative
      selection. Using a combined model for the evolution of noncoding and coding
      regions, we develop two likelihood-ratio tests for the detection of selection in
      noncoding regions. Data analysis of both simulated and real viral data is
      presented. Using the new method we show that positive selection in viruses is
      acting primarily in protein-coding regions and is rare or absent in noncoding
      regions.

PMID- 15238544
TI  - A quantitative trait locus mixture model that avoids spurious LOD score peaks.
AB  - In standard interval mapping of quantitative trait loci (QTL), the QTL effect is
      described by a normal mixture model. At any given location in the genome, the
      evidence of a putative QTL is measured by the likelihood ratio of the mixture
      model compared to a single normal distribution (the LOD score). This approach can
      occasionally produce spurious LOD score peaks in regions of low genotype
      information (e.g., widely spaced markers), especially if the phenotype
      distribution deviates markedly from a normal distribution. Such peaks are not
      indicative of a QTL effect; rather, they are caused by the fact that a mixture of
      normals always produces a better fit than a single normal distribution. In this
      study, a mixture model for QTL mapping that avoids the problems of such spurious
      LOD score peaks is presented.

PMID- 15238545
TI  - A unified Markov chain Monte Carlo framework for mapping multiple quantitative
      trait loci.
AB  - In this article, a unified Markov chain Monte Carlo (MCMC) framework is proposed
      to identify multiple quantitative trait loci (QTL) for complex traits in
      experimental designs, based on a composite space representation of the problem
      that has fixed dimension. The proposed unified approach includes the existing
      Bayesian QTL mapping methods using reversible jump MCMC algorithm as special
      cases. We also show that a variety of Bayesian variable selection methods using
      Gibbs sampling can be applied to the composite model space for mapping multiple
      QTL. The unified framework not only results in some new algorithms, but also
      gives useful insight into some of the important factors governing the performance
      of Gibbs sampling and reversible jump for mapping multiple QTL. Finally, we
      develop strategies to improve the performance of MCMC algorithms.

PMID- 15238546
TI  - Comparative evaluation of a new effective population size estimator based on
      approximate bayesian computation.
AB  - We describe and evaluate a new estimator of the effective population size (N(e)),
      a critical parameter in evolutionary and conservation biology. This new
      "SummStat" N(e) estimator is based upon the use of summary statistics in an
      approximate Bayesian computation framework to infer N(e). Simulations of a Wright
      Fisher population with known N(e) show that the SummStat estimator is useful
      across a realistic range of individuals and loci sampled, generations between
      samples, and N(e) values. We also address the paucity of information about the
      relative performance of N(e) estimators by comparing the SummStat estimator to
      two recently developed likelihood-based estimators and a traditional moment-based
      estimator. The SummStat estimator is the least biased of the four estimators
      compared. In 32 of 36 parameter combinations investigated using initial allele
      frequencies drawn from a Dirichlet distribution, it has the lowest bias. The
      relative mean square error (RMSE) of the SummStat estimator was generally
      intermediate to the others. All of the estimators had RMSE > 1 when small samples
      (n = 20, five loci) were collected a generation apart. In contrast, when samples
      were separated by three or more generations and N(e) < or = 50, the SummStat and
      likelihood-based estimators all had greatly reduced RMSE. Under the conditions
      simulated, SummStat confidence intervals were more conservative than the
      likelihood-based estimators and more likely to include true N(e). The greatest
      strength of the SummStat estimator is its flexible structure. This flexibility
      allows it to incorporate any potentially informative summary statistic from
      population genetic data.

PMID- 15238547
TI  - Modifying the Schwarz Bayesian information criterion to locate multiple
      interacting quantitative trait loci.
AB  - The problem of locating multiple interacting quantitative trait loci (QTL) can be
      addressed as a multiple regression problem, with marker genotypes being the
      regressor variables. An important and difficult part in fitting such a regression
      model is the estimation of the QTL number and respective interactions. Among the
      many model selection criteria that can be used to estimate the number of
      regressor variables, none are used to estimate the number of interactions. Our
      simulations demonstrate that epistatic terms appearing in a model without the
      related main effects cause the standard model selection criteria to have a strong
      tendency to overestimate the number of interactions, and so the QTL number. With
      this as our motivation we investigate the behavior of the Schwarz Bayesian
      information criterion (BIC) by explaining the phenomenon of the overestimation
      and proposing a novel modification of BIC that allows the detection of main
      effects and pairwise interactions in a backcross population. Results of an
      extensive simulation study demonstrate that our modified version of BIC performs
      very well in practice. Our methodology can be extended to general populations and
      higher-order interactions.

PMID- 15238548
TI  - Joint effects of self-fertilization and population structure on mutation load,
      inbreeding depression and heterosis.
AB  - Both the spatial distribution of organisms and their mode of reproduction have
      important effects on the change in allele frequencies within populations. In this
      article, we study the combined effect of population structure and the rate of
      partial selfing of organisms on the efficiency of selection against recurrent
      deleterious mutations. Assuming an island model of population structure and weak
      selection, we express the mutation load, the within- and between-deme inbreeding
      depression, and heterosis as functions of the frequency of deleterious mutants in
      the metapopulation; we then use a diffusion model to calculate an expression for
      the equilibrium probability distribution of this frequency of deleterious
      mutants. This allows us to derive approximations for the average mutant
      frequency, mutation load, inbreeding depression, and heterosis, the simplest ones
      being Equations 35-39 in the text. We find that population structure can help to
      purge recessive deleterious mutations and reduce the load for some parameter
      values (in particular when the dominance coefficient of these mutations is <0.2
      0.3), but that this effect is reversed when the selfing rate is above a given
      value. Conversely, within-deme inbreeding depression always decreases, while
      heterosis always increases, with the degree of population subdivision, for all
      selfing rates.

PMID- 15238549
TI  - Mapping quantitative trait Loci interactions from the maternal and offspring
      genomes.
AB  - The expression of most developmental or behavioral traits involves complex
      interactions between quantitative trait loci (QTL) from the maternal and
      offspring genomes. The maternal-offspring interactions play a pivotal role in
      shaping the direction and rate of evolution in terms of their substantial
      contribution to quantitative genetic (co)variation. To study the genetics and
      evolution of maternal-offspring interactions, a unifying statistical framework
      that embraces both the direct and indirect genetic effects of maternal and
      offspring QTL on any complex trait is developed. This model is derived for a
      simple backcross design within the maximum-likelihood context, implemented with
      the EM algorithm. Results from extensive simulations suggest that this model can
      provide reasonable estimation of additive and dominant effects of the QTL at
      different generations and their interaction effects derived from the maternal and
      offspring genomes. Although our model is framed to characterize the actions and
      interactions of maternal and offspring QTL affecting offspring traits, the idea
      can be readily extended to decipher the genetic machinery of maternal traits,
      such as maternal care. Our model provides a powerful means for studying the
      evolutionary significance of indirect genetic effects in any sexually
      reproductive organisms.

PMID- 15238551
TI  - How common are overdominant mutations?

PMID- 15238550
TI  - Assessing the relative rate of (mitochondrial) genomic change.
AB  - I report a framework for assessing whether one mitochondrial genome is
      significantly more rearranged than another. This relative rate of gene
      rearrangement test (RGR) behaves according to expectation, distinguishing between
      highly rearranged and mildly rearranged insect mitochondrial genomes. It may be
      more broadly applied to assess the relative rate of nuclear gene rearrangement.

PMID- 15238552
TI  - Reversible-jump Markov chain Monte Carlo for quantitative trait loci mapping.

PMID- 15238553
TI  - Comment on "On the Metropolis-Hastings acceptance probability to add or drop a
      quantitative trait locus in Markov chain Monte Carlo-based Bayesian analyses".

PMID- 15238554
TI  - Microalbuminuria in cats.

PMID- 15238555
TI  - Repetitive propofol administration in dogs and cats.
AB  - A bolus of propofol was administered to 10 dogs (6 mg/kg intravenously [IV]) and
      10 cats (10 mg/kg IV) on three consecutive days. The occurrence of apnea, heart
      and respiratory rates, blood pressure, time to movement, and changes in a
      complete blood count and biochemical profile were recorded. Apnea was not seen in
      the dogs but was seen in three cats. Slight increases in the number of Heinz
      bodies were seen in six cats, but the increases were not considered clinically
      significant. No apparent cumulative adverse effects were seen from a bolus of
      bisulfite-containing propofol, administered on three consecutive days.

PMID- 15238556
TI  - Placebo-controlled clomipramine trial for the treatment of feather picking
      disorder in cockatoos.
AB  - This double-blind, placebo-controlled trial was performed to evaluate the
      efficacy of clomipramine for the treatment of feather picking disorder in
      otherwise healthy cockatoos. Twenty cockatoos with chronic feather picking
      disorder were screened for medical conditions and then randomly assigned to
      either a clomipramine or placebo group. Based on caregiver assessments and
      physical examination findings, treatment with clomipramine significantly improved
      feather picking when compared to a placebo at 3 weeks (P=0.028) and at 6 weeks
      (P=0.021). Clomipramine had no significant effect, however, on videotaped
      preening behaviors.

PMID- 15238557
TI  - Correlations of fatty acid supplementation, aeroallergens, shampoo, and ear
      cleanser with multiple parameters in pruritic dogs.
AB  - Seventy-two pruritic dogs were fed one of four diets controlled for n-6:n-3 fatty
      acid ratios and total dietary intake of fatty acids. Multiple parameters were
      evaluated, including clinical and cytological findings, aeroallergen testing,
      microbial sampling techniques, and effects of an anti-fungal/antibacterial
      shampoo and ear cleanser. Significant correlations were observed between many
      clinical parameters, anatomical sampling sites, and microbial counts when data
      from the diet groups was combined. There were no statistically significant
      differences between individual diets for any of the clinical parameters. The
      importance of total clinical management in the control of pruritus was
      demonstrated.

PMID- 15238558
TI  - Zonisamide therapy for refractory idiopathic epilepsy in dogs.
AB  - Twelve dogs with poorly controlled idiopathic epilepsy were entered into a
      prospective, open-label, noncomparative study. Oral zonisamide was administered
      as an additional therapy at a dosage adequate to achieve serum drug
      concentrations of 10 to 40 microg/mL. Seizure frequency before and after
      initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours
      was sufficient to maintain serum zonisamide concentrations within the therapeutic
      range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven
      (58%) dogs responded favorably, experiencing a mean reduction in seizures of
      81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g.,
      transient sedation, ataxia, vomiting) occurred in six dogs.

PMID- 15238559
TI  - Carmustine, vincristine, and prednisone in the treatment of canine lymphosarcoma.
AB  - A chemotherapeutic protocol using carmustine in combination with vincristine and
      prednisone was tested in dogs with multicentric malignant lymphosarcoma. Of seven
      dogs treated, six (85.7%) achieved complete remission. A partial response
      occurred in one dog. Median survival time was 224 days (mean 386 days), and
      median duration of remission was 183 days (mean 323 days). Marked neutropenia was
      observed following carmustine administration. There were no significant
      alterations in platelets and red blood cell counts during treatment, and no
      abnormalities attributable to the chemotherapy were found in serum biochemical
      profiles. Results of this study showed that carmustine is an effective
      alternative option in the treatment of canine lymphosarcoma.

PMID- 15238560
TI  - Postoperative assessment of surgical clip position in 16 dogs with cancer: a
      pilot study.
AB  - Metallic hemoclips or surgical staples were inserted in 16 tumor-bearing dogs at
      the time of surgical resection of the tumor. Orthogonal radiographs were taken
      immediately postoperatively and after wound healing to visualize the location and
      number of hemoclips or metallic staples. A shift in hemoclip/staple position was
      identified in nine dogs, mainly from positioning during radiography. In three
      dogs, an absolute shift in marker position was identified. Based on this study,
      it appears that the placement of surgical clips is potentially useful in
      identifying the tumor bed, which may be of benefit in establishing radiation
      treatment fields.

PMID- 15238561
TI  - Iridium-192 interstitial brachytherapy as adjunctive treatment for canine
      cutaneous mast cell tumors.
AB  - Eleven dogs with cutaneous mast cell tumors (MCTs) were treated with surgery and
      iridium-192 ((192)Ir) interstitial brachytherapy. Minimum tumor doses ranged from
      47.2 to 63.3 Gy. Treated tumors were classified as grade II (n=7) or III (n=4).
      Five dogs had recurrences with a median progression-free interval of 1391 days,
      and six dogs had no recurrence at a median follow-up time of 942 days. Acute
      adverse effects were well tolerated, and late effects were mild. One dog
      developed a second tumor of a different cell type in the radiation treatment
      field.

PMID- 15238562
TI  - A retrospective comparison of cervical intervertebral disk disease in
      nonchondrodystrophic large dogs versus small dogs.
AB  - Medical records of 144 small-breed dogs (< or =15 kg) and 46 medium- to large
      breed dogs (>15 kg) with surgically confirmed, Hansen type I, cervical
      intervertebral disk extrusions were reviewed. The most common clinical
      presentation was cervical hyperesthesia. The most common sites affected were the
      second (C(2)) to third (C(3)) cervical intervertebral disk space in small-breed
      dogs and the sixth (C(6)) to seventh (C(7)) cervical intervertebral disk space in
      the larger dogs. Following surgery, 99% of the dogs had resolution of cervical
      hyperesthesia and were able to ambulate unassisted. Seven (4%) dogs required a
      second surgery; four of these were large-breed dogs.

PMID- 15238563
TI  - Arthroscopic release of the medial femoropatellar ligament for canine medial
      patellar luxation.
AB  - Five dogs of varying breeds and ages were presented for evaluation of medial
      patellar luxation that was unresponsive to conservative treatment. Arthroscopy of
      each affected stifle was performed, and adequacy of the femoral trochlea and
      patellar tracking in the trochlea were assessed. Medial femoropatellar ligament
      release was then performed using a bipolar radiofrequency electrosurgical system
      with or without a tibial tuberosity transposition. The procedure resulted in good
      to excellent outcomes for four dogs and a fair outcome for a fifth dog.

PMID- 15238564
TI  - Major glossectomy in dogs: a case series and proposed classification system.
AB  - Major resections of the tongue have not been commonly performed in animals
      because of concerns about the unfavorable postoperative effects of diminished
      lingual function. Five dogs were retrospectively reviewed to determine prehensile
      function and quality of life after glossectomies. Examinations were performed 1
      week to 8 years after glossectomy, and owner interviews were conducted 10 months
      to 8 years after the surgery. All five dogs had acceptable and functional
      outcomes. Based on these five cases, glossectomy was well tolerated by dogs and
      may be a viable treatment option for aggressive tongue tumors and other
      conditions that render the tongue unsalvageable.

PMID- 15238565
TI  - Asymmetrical, transitional, lumbosacral vertebral segments in six dogs: a
      characteristic spinal syndrome.
AB  - Clinical findings in six dogs with asymmetrical, transitional, lumbosacral
      vertebral segments are reported. All dogs exhibited low back pain and varying
      degrees of asymmetrical cauda equina dysfunction. Results of myelography,
      epidurography, and magnetic resonance imaging (MRI) indicated a unilateral disk
      protrusion in all dogs. In the dogs with MRIs, focal degenerative alterations in
      the vertebral end plates and adjacent body of the vertebra were detected. All
      dogs were treated with a dorsal laminectomy or hemilaminectomy. Results following
      surgery were good or excellent in all six dogs.

PMID- 15238566
TI  - Fatal intraoperative pulmonary fat embolism during cemented total hip
      arthroplasty in a dog.
AB  - A 3-year-old, German shepherd dog died suddenly during cemented total hip
      arthroplasty. Gross necropsy findings included severe pulmonary edema and
      congestion as well as congestion of the liver and kidneys. Acute pulmonary
      embolism was suspected as the cause of death. Microscopic examination of
      hematoxylin and eosin-stained, formalin-fixed, and oil red O-stained frozen
      tissue sections confirmed the presence of large numbers of fat globules in blood
      vessels in the lungs, liver, and kidneys. Fat embolism during total hip
      arthroplasty is a common surgical complication in humans, but it is uncommon in
      veterinary cases and is rarely a cause of death.

PMID- 15238567
TI  - Trial of preventing hypertension: design and 2-year progress report.
AB  - The TRial Of Preventing HYpertension (TROPHY) study is an investigator-initiated
      trial to examine whether early pharmacological treatment in subjects with "high
      normal" blood pressure (BP) might prevent or delay the development of clinical
      hypertension. This is a 4-year, multicenter, randomized, double-blind study in
      untreated subjects aged 30 to 65 years with entry BPs of 130 to 139/< or =89 or <
      or =139/85 to 89. The participants were randomized either to placebo or to a
      fixed (16 mg once daily) dose of candesartan cilexetil (candesartan). After 2
      years, the candesartan group was switched to placebo, and the placebo group
      continued taking placebo. The main outcome measure was the development of
      clinical (treatment-requiring) hypertension assessed by an automated (blinded) BP
      measurement device. We randomized 809 subjects (59% males, average age 49.0+/-SD
      8.1 years) in 71 study centers in the United States. The entry BP was 134+/
      4.3/84.8+/-3.9 mm Hg. During the first 2 years, 187 subjects (23%) developed
      clinical hypertension. All have been given antihypertensive treatment, and 170
      continue to be followed in study centers. The study dropout rate is 14.8% (120
      subjects). The hypertension rates are higher than anticipated, whereas the rates
      of dropout are within the sample size projections; thus, the study will have
      sufficient power to evaluate its hypotheses. In this article, we describe
      baseline characteristics of TROPHY subjects and discuss novel analytical issues
      and statistical approaches to evaluate the findings in this trial of primary
      prevention of hypertension.

PMID- 15238568
TI  - Genetic variation in CYP11B2 and AT1R influences heart rate variability
      conditional on sodium excretion.
AB  - Sympathetic tone increases with stimulation of the renin-angiotensin system and
      is under the influence of salt intake. In the European Project On Genes in
      Hypertension (EPOGH), we investigated whether polymorphisms in the genes encoding
      aldosterone synthase (CYP11B2 C-344T) and the type-1 angiotensin II receptor
      (AT1R A1166C) affect the autonomic modulation of heart rate at varying levels of
      salt intake. We measured the low frequency (LF) and high frequency (HF)
      components of heart rate variability and their ratio (LF:HF) in the supine and
      standing positions in 1797 participants (401 families and 320 unrelated subjects)
      randomly selected from 6 European populations, whose average urinary sodium
      excretion ranged from 163 to 245 mmol/d. In multivariate analyses with sodium
      excretion analyzed as a continuous variable, we explored the phenotype-genotype
      associations using generalized estimating equations and quantitative transmission
      disequilibrium tests. Across populations, there was no heterogeneity in the
      phenotype-genotype relations. The genotypic effects differed according to sodium
      excretion. In subjects with sodium excretion <190 mmol/d (median), supine heart
      rate, LF, and LF:HF increased and HF decreased with the number of CYP11B2 -344T
      alleles, and the orthostatic changes in LF, HF, and LF:HF were blunted in
      carriers of the AT1R 1166C allele. In subjects with sodium excretion >190 mmol/d,
      these associations with the CYP11B2 and AT1R polymorphisms were nonsignificant or
      in the opposite direction, respectively. Thus, CYP11B2 C-344T and AT1R A1166C
      polymorphisms affect the autonomic modulation of heart rate, but these genetic
      effects depend on sodium excretion.

PMID- 15238569
TI  - Safety evaluation of clinical gene therapy using hepatocyte growth factor to
      treat peripheral arterial disease.
AB  - Therapeutic angiogenesis using angiogenic growth factors is expected to be a new
      treatment for patients with critical limb ischemia (CLI). Because hepatocyte
      growth factor (HGF) has potent angiogenic activity, we investigated the safety
      and efficiency of HGF plasmid DNA in patients with CLI as a prospective open
      labeled clinical trial. Intramuscular injection of naked HGF plasmid DNA was
      performed in ischemic limbs of 6 CLI patients with arteriosclerosis obliterans
      (n=3) or Buerger disease (n=3) graded as Fontaine III or IV. The primary end
      points were safety and improvement of ischemic symptoms at 12 weeks after
      transfection. Severe complications and adverse effects caused by gene transfer
      were not detected in any patients. Of particular importance, no apparent edema
      was observed in any patient throughout the trial. In addition, serum HGF
      concentration was not changed throughout the therapy period in all patients. In
      contrast, a reduction of pain scale of more than 1 cm in visual analog pain scale
      was observed in 5 of 6 patients. Increase in ankle pressure index more than 0.1
      was observed in 5 of 5 patients. The long diameter of 8 of 11 ischemic ulcers in
      4 patients was reduced >25%. Intramuscular injection of naked HGF plasmid is
      safe, feasible, and can achieve successful improvement of ischemic limbs.
      Although the present data are conducted to demonstrate the safety as phase
      I/early phase IIa, the initial clinical outcome with HGF gene transfer seems to
      indicate usefulness as sole therapy for CLI.

PMID- 15238570
TI  - Atorvastatin prevents end-organ injury in salt-sensitive hypertension: role of
      eNOS and oxidant stress.
AB  - Statins, inhibitors of cholesterol biosynthesis, are endowed with pleiotropic
      effects that may contribute to their favorable clinical results. Hypertensive
      Dahl salt-sensitive (DS) rats have endothelial dysfunction and cardiorenal injury
      associated with decreased NO bioavailability and increased superoxide (O2-)
      production linked to a functional upregulation of angiotensin II. We investigated
      whether atorvastatin (30 mg/kg per day; by gavage) would prevent endothelial
      nitric oxide (eNOS) downregulation and the increase in O2- in DS rats, thereby
      reducing end-organ injury. DS rats given a high-salt diet (4% NaCl) for 10 weeks
      developed hypertension (systolic blood pressure [SBP] 200+/-8 versus 150+/-2 mm
      Hg in DS rats fed 0.5% NaCl diet [NS]; P<0.05), impaired endothelium-dependent
      relaxation, functional upregulation of endothelin-1, left ventricular hypertrophy
      (LVH; 30%), and proteinuria (167%), accompanied by downregulation of aortic eNOS
      activity (0.7+/-0.2 versus 1.8+/-0.3 nmol/min per gram protein in NS; P<0.05) and
      increased aortic O2- (2632+/-316 versus 1176+/-112 counts/min per milligram in
      NS; P<0.05) and plasma 8-F2alpha isoprostanes. Atorvastatin prevented the
      decrease in eNOS activity (1.5+/-0.3 nmol/min per gram protein) as well as the
      increase in O2- (1192+/-243 counts/min per milligram) and plasma 8-F2alpha
      isoprostanes, reduced LVH and proteinuria, and normalized endothelial function
      and vascular response to endothelin-1, although reduction in SBP was modest
      (174+/-8 mm Hg). Atorvastatin combined with removal of high salt normalized
      aortic eNOS activity, SBP, LVH, and proteinuria. These findings strongly suggest
      that concomitant prevention of vascular eNOS downregulation and inhibition of
      oxidative stress may contribute to the protection against end-organ injury
      afforded by this statin in salt-sensitive hypertension.

PMID- 15238571
TI  - A piece of my mind. Tomorrow.

PMID- 15238572
TI  - Impact of long working hours explored.

PMID- 15238573
TI  - WHO meeting targets AIDS, other issues.

PMID- 15238574
TI  - Chimpanzees and humans: not so close?

PMID- 15238575
TI  - Monoclonal antibodies target inflammatory bowel disease.

PMID- 15238576
TI  - Rapid anthrax test approved.

PMID- 15238580
TI  - Aggressive lipid-lowering therapy and regression of coronary atheroma.

PMID- 15238581
TI  - Aggressive lipid-lowering therapy and regression of coronary atheroma.

PMID- 15238582
TI  - Aggressive lipid-lowering therapy and regression of coronary atheroma.

PMID- 15238583
TI  - Aggressive lipid-lowering therapy and regression of coronary atheroma.

PMID- 15238584
TI  - Adiponectin and risk of coronary heart disease.

PMID- 15238585
TI  - Sex differences in mortality after coronary artery bypass graft surgery.

PMID- 15238586
TI  - Atrial fibrillation and risk of postoperative complications.

PMID- 15238587
TI  - Interventions for hypochondriasis in primary care.

PMID- 15238588
TI  - Inflammation and age-related macular degeneration.

PMID- 15238589
TI  - Meta-analysis of health outcomes of chlorthalidone-based vs nonchlorthalidone
      based low-dose diuretic therapies.

PMID- 15238590
TI  - Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment
      elevation acute coronary syndromes managed with an intended early invasive
      strategy: primary results of the SYNERGY randomized trial.
AB  - CONTEXT: Enoxaparin has demonstrated advantages over unfractionated heparin in
      low- to moderate-risk patients with non-ST-segment elevation acute coronary
      syndromes (ACS) treated with a conservative strategy. OBJECTIVES: To compare the
      outcomes of patients treated with enoxaparin vs unfractionated heparin and to
      define the role of enoxaparin in patients with non-ST-segment elevation ACS at
      high risk for ischemic cardiac complications managed with an early invasive
      approach. DESIGN, SETTING, AND PARTICIPANTS: The Superior Yield of the New
      Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors
      (SYNERGY) trial was a prospective, randomized, open-label, multicenter,
      international trial conducted between August 2001 and December 2003. A total of
      10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an
      intended early invasive strategy were recruited. INTERVENTIONS: Subcutaneous
      enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be
      administered immediately after enrollment and continued until the patient
      required no further anticoagulation, as judged by the treating physician. MAIN
      OUTCOME MEASURES: The primary efficacy outcome was the composite clinical end
      point of all-cause death or nonfatal myocardial infarction during the first 30
      days after randomization. The primary safety outcome was major bleeding or
      stroke. RESULTS: The primary end point occurred in 14.0% (696/4993) of patients
      assigned to enoxaparin and 14.5% (722/4985) of patients assigned to
      unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86
      1.06). No differences in ischemic events during percutaneous coronary
      intervention (PCI) were observed between enoxaparin and unfractionated heparin
      groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%]
      vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]),
      unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery
      bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed
      with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis
      in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but
      nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for
      Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0%
      vs 16.0%, P =.16). CONCLUSIONS: Enoxaparin was not superior to unfractionated
      heparin but was noninferior for the treatment of high-risk patients with non-ST
      segment elevation ACS. Enoxaparin is a safe and effective alternative to
      unfractionated heparin and the advantages of convenience should be balanced with
      the modest excess of major bleeding.

PMID- 15238591
TI  - Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non
      ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin:
      a randomized controlled trial.
AB  - CONTEXT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor
      tirofiban with unfractionated heparin independently have shown superior efficacy
      over unfractionated heparin alone in patients with non-ST-elevation acute
      coronary syndromes (ACS). It is not clear if combining enoxaparin with
      glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current
      standard combination of unfractionated heparin with glycoprotein IIb/IIIa
      inhibitors. OBJECTIVE: To assess efficacy and safety of the combination of
      enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in
      patients with non-ST-elevation ACS. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective, international, open-label, randomized, noninferiority trial of 1
      mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted
      intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation
      ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted
      between December 1999 and May 2002. MAIN OUTCOME MEASURES: Death, recurrent
      myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat
      population with boundaries set for superiority and noninferiority. Safety based
      on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI)
      classification system. RESULTS: A total of 169 (8.4%) of 2018 patients randomized
      to enoxaparin experienced death, myocardial infarction, or refractory ischemia at
      7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated
      heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This
      met the prespecified criterion for noninferiority. All components of the
      composite primary and secondary end points favored enoxaparin except death, which
      occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated
      heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and
      2.2% for unfractionated heparin; P =.13). Using a worst-case approach that
      combined 2 independent bleeding evaluations, use of enoxaparin was associated
      with 1 additional TIMI major bleeding episode for each 200 patients treated.
      CONCLUSIONS: In patients receiving tirofiban and aspirin, enoxaparin is a
      suitable alternative to unfractionated heparin for treatment of non-ST-elevation
      ACS. The 12% relative and 1% absolute reductions in the primary end point in
      favor of enoxaparin met criterion for noninferiority and are consistent with
      prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.

PMID- 15238592
TI  - Effect of soy protein containing isoflavones on cognitive function, bone mineral
      density, and plasma lipids in postmenopausal women: a randomized controlled
      trial.
AB  - CONTEXT: Postmenopausal estrogen therapy has been posited to have some beneficial
      effects on aging processes, but its use has risks. Isoflavones, estrogenlike
      compounds naturally occurring in plant foods, might confer positive effects with
      fewer adverse effects. OBJECTIVE: To investigate whether soy protein with
      isoflavones improves cognitive function, bone mineral density, and plasma lipids
      in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Double-blind,
      randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60
      to 75 years, recruited from a population-based sample in the Netherlands,
      conducted between April 2000 and September 2001. INTERVENTION: Participants were
      randomly assigned to receive 25.6 g of soy protein containing 99 mg of
      isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk
      protein as a powder on a daily basis for 12 months. MAIN OUTCOME MEASURES:
      Cognitive function was assessed using the following instruments: dementia, Mini
      Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate
      recall, delayed recall, and recognition, the Digit Span forward and reversed, and
      the Doors test; complex attention tasks, Digit Symbol Substitution and
      Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals
      and occupations, and the Boston Naming Task. Bone mineral density of the hip and
      lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid
      assessment included lipoprotein(a), total cholesterol, low-density lipoprotein,
      high-density lipoprotein, and triglycerides. RESULTS: A total of 175 women
      completed the baseline and at least 1 postintervention analysis and were included
      in the modified intent-to-treat analysis. Adherence was good (median plasma
      genistein levels, 17.2 and 615.1 nmol/L for placebo and soy group, respectively).
      Cognitive function, bone mineral density, or plasma lipids did not differ
      significantly between the groups after a year. CONCLUSION: This double-blind
      randomized trial does not support the hypothesis that the use of soy protein
      supplement containing isoflavones improves cognitive function, bone mineral
      density, or plasma lipids in healthy postmenopausal women when started at the age
      of 60 years or later.

PMID- 15238593
TI  - Transfer of fetal cells with multilineage potential to maternal tissue.
AB  - CONTEXT: During pregnancy, fetal CD34+ cells enter the maternal circulation,
      persist for decades, and create a state of physiologic microchimerism. Many
      studies have confirmed the residual presence of fetal cells in maternal blood and
      tissues following pregnancy. Fetal cells may respond to maternal injury by
      developing multilineage capacity in maternal organs. OBJECTIVE: To verify that
      fetal microchimeric cells express markers of epithelial, leukocyte, and
      hepatocyte differentiation within maternal organs. DESIGN, SETTING, AND PATIENTS:
      Archived paraffin-embedded tissue section specimens from 10 women who had male
      offspring and were previously found to have high numbers of microchimeric cells,
      and 11 control women who had no prior male pregnancies. Male cells were
      identified by fluorescence in situ hybridization, using X and Y chromosome
      specific probes, followed by histologic and immunochemical studies using
      anticytokeratin (AE1/AE3) as a marker of epithelial cells, anti-CD45 as a
      leukocyte marker, and heppar-1 as a hepatocyte marker. MAIN OUTCOME MEASURE:
      Percentage of microchimeric cells expressing nonhematopoietic markers. RESULTS: A
      total of 701 male (XY+) microchimeric cells were identified (mean [SD], 227 [128]
      XY+ cells per million maternal cells). In maternal epithelial tissues (thyroid,
      cervix, intestine, and gallbladder), 14% to 60% of XY+ cells expressed
      cytokeratin. Conversely, in hematopoietic tissues, such as lymph nodes and
      spleen, 90% of XY+ cells expressed CD45. In 1 liver sample, 4% of XY+ cells
      expressed heppar-1. Histologic and immunochemical evidence of differentiation, as
      assessed by independent observers, was highly concordant (kappa = 0.72).
      CONCLUSION: The detection of microchimeric male cells, bearing epithelial,
      leukocyte, or hepatocyte markers, in a variety of maternal tissue specimens
      suggests the presence of fetal cells that may have multilineage capacity.

PMID- 15238594
TI  - Endometrial cells derived from donor stem cells in bone marrow transplant
      recipients.
AB  - CONTEXT: Regeneration of the endometrium in each menstrual cycle is required for
      reproduction. Endogenous endometrial stem cells reside in the basalis layer and
      serve as a source of cells that differentiate to form the endometrium. Bone
      marrow-derived cells have been shown to take on functions outside the
      hematopoietic system. OBJECTIVE: To investigate the possibility that cells of
      extrauterine origin could repopulate the endometrium. DESIGN, SETTING, AND
      PATIENTS: Endometrium from 4 HLA-mismatched bone marrow transplant recipients
      (1998-2002) was evaluated for donor HLA expression. Each recipient had a bone
      marrow donor with an HLA type that enabled determination of the origin of any
      cell. Endometrial biopsies also were obtained from 4 healthy control women. MAIN
      OUTCOME MEASURE: HLA type was determined by immunohistochemistry and by reverse
      transcription-polymerase chain reaction. RESULTS: Donor-derived endometrial cells
      were detected in endometrial biopsy samples from all bone marrow recipients and
      accounted for 0.2% to 48% of epithelial cells and 0.3% to 52% of stromal cells.
      None of the controls demonstrated HLA mismatch in endometrial samples.
      CONCLUSION: These findings demonstrate that endometrial cells can originate from
      donor-derived bone marrow cells and suggest that nonuterine stem cells contribute
      to the regeneration of endometrial tissue.

PMID- 15238595
TI  - Authorship criteria and disclosure of contributions: comparison of 3 general
      medical journals with different author contribution forms.
AB  - CONTEXT: A number of general medical journals and the International Committee of
      Medical Journal Editors (ICMJE) request authors to disclose their contributions.
      Little is known about the effect of journal policies on authors' disclosure of
      their contributions. OBJECTIVE: To determine the number of named authors who do
      not meet ICMJE criteria for authorship, according to their published
      contributions, in 3 medical journals with different contribution disclosure
      practices. DESIGN: Observational study of authors' contributions in research
      articles published in 2002 in Annals of Internal Medicine (n = 72), BMJ (n =
      107), and JAMA (n = 81). BMJ asks authors to describe research contributions in
      their own words; Annals asks authors to choose from a list of coded
      contributions; and JAMA uses a structured checklist with instructions on
      contributions that qualify for ICMJE authorship criteria. Honorary authorship was
      defined as the lack of contribution from the first ICMJE criterion (study
      conception and design, or acquisition of data, or analysis and interpretation of
      data) and/or second (drafting the article or critical revision for important
      intellectual content) ICMJE criterion. RESULTS: According to authors' published
      contributions, the number of honorary authors was highest in Annals (121/562
      authors, 21.5%), followed by BMJ (46/482, 9.5%), and JAMA (3/641, 0.5%) (chi2(2)
      = 146.67, P<.001). The number of articles with honorary authors was 60% in
      Annals, 21% in BMJ, and 4% in JAMA. Honorary authors had fewer published
      contributions than authors who met ICMJE criteria and were positioned more toward
      the end of the byline. Honorary authors either lacked contributions for both
      ICMJE criteria (10% in Annals and 22% in BMJ) or contributions to the second
      ICMJE criterion (75% in Annals, 67% in BMJ, and 2 out of 3 in JAMA). CONCLUSIONS:
      General medical journals differed in prevalence of honorary authors according to
      published research contributions of named authors. Different
      authorship/contributorship policies and procedures should be explored as a
      possible explanation for the differences in contributions disclosed by authors
      among these journals.

PMID- 15238596
TI  - Efficacy and bleeding complications among patients randomized to enoxaparin or
      unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute
      coronary syndromes: a systematic overview.
AB  - CONTEXT: Antithrombin therapy has become a guidelines-recommended standard of
      care in the treatment of acute coronary syndromes (ACS), but recent trials
      comparing use of enoxaparin and unfractionated heparin in ACS have yielded less
      robust efficacy and safety results than have earlier trials of these antithrombin
      therapies. OBJECTIVE: To systematically evaluate the end points of all-cause
      death and nonfatal myocardial infarction (MI), transfusion, and major bleeding
      observed in the 6 randomized controlled trials comparing enoxaparin and
      unfractionated heparin in treatment of ACS. DATA SOURCES: The primary data sets
      for ESSENCE, A to Z, and SYNERGY were available at the Duke Clinical Research
      Institute. Baseline characteristics and event frequencies for TIMI 11B, ACUTE II,
      and INTERACT were provided by the principal investigator of each study. STUDY
      SELECTION: All 6 randomized controlled trials comparing enoxaparin and
      unfractionated heparin in non-ST-segment elevation ACS were selected for
      analysis. DATA EXTRACTION: Efficacy and safety end points were extracted from the
      overall trial populations and the subpopulation receiving no antithrombin therapy
      prior to randomization. DATA SYNTHESIS: Systematic evaluation of the outcomes for
      21 946 patients was performed using a random-effects empirical Bayes model. No
      significant difference was found in death at 30 days for enoxaparin vs
      unfractionated heparin (3.0% vs 3.0%; odds ratio [OR], 1.00; 95% confidence
      interval [CI], 0.85-1.17). A statistically significant reduction in the combined
      end point of death or nonfatal MI at 30 days was observed for enoxaparin vs
      unfractionated heparin in the overall trial populations (10.1% vs 11.0%; OR,
      0.91; 95% CI, 0.83-0.99; number needed to treat, 107). A statistically
      significant reduction in the combined end point of death or MI at 30 days was
      also observed for enoxaparin in the populations receiving no prerandomization
      antithrombin therapy (8.0% vs 9.4%; OR, 0.81; 95% CI, 0.70-0.94; number needed to
      treat, 72). No significant difference was found in blood transfusion (OR, 1.01;
      95% CI, 0.89-1.14) or major bleeding (OR, 1.04; 95% CI, 0.83-1.30) at 7 days
      after randomization in the overall safety population or in the population of
      patients receiving no prerandomization antithrombin therapy. CONCLUSION: In a
      systematic overview of approximately 22 000 patients across the spectrum of ACS,
      enoxaparin is more effective than unfractionated heparin in preventing the
      combined end point of death or MI.

PMID- 15238597
TI  - Renal cell carcinoma.

PMID- 15238598
TI  - Fractionating heparins and their clinical trial data--something for everyone.

PMID- 15238599
TI  - Stem cell transfer and the uterus: the egg teaches the chicken.

PMID- 15238600
TI  - JAMA patient page. Kidney cancer.

PMID- 15238601
TI  - An improved model for prediction of retention times of tryptic peptides in ion
      pair reversed-phase HPLC: its application to protein peptide mapping by off-line
      HPLC-MALDI MS.
AB  - The proposed model is based on the measurement of the retention times of 346
      tryptic peptides in the 560- to 4,000-Da mass range, derived from a mixture of 17
      protein digests. These peptides were measured in HPLC-MALDI MS runs, with peptide
      identities confirmed by MS/MS. The model relies on summation of the retention
      coefficients of the individual amino acids, as in previous approaches, but
      additional terms are introduced that depend on the retention coefficients for
      amino acids at the N-terminal of the peptide. In the 17-protein mixture,
      optimization of two sets of coefficients, along with additional compensation for
      peptide length and hydrophobicity, yielded a linear dependence of retention time
      on hydrophobicity, with an R2 value about 0.94. The predictive capability of the
      model was used to distinguish peptides with close m/z values and for detailed
      peptide mapping of selected proteins. Its applicability was tested on columns of
      different sizes, from nano- to narrow-bore, and for direct sample injection, or
      injection via a pre-column. It can be used for accurate prediction of retention
      times for tryptic peptides on reversed-phase (300-A pore size) columns of
      different sizes with a linear water-ACN gradient and with TFA as the ion-pairing
      modifier.

PMID- 15238602
TI  - Integrated genomic and proteomic analyses of gene expression in Mammalian cells.
AB  - Using DNA microarrays together with quantitative proteomic techniques (ICAT
      reagents, two-dimensional DIGE, and MS), we evaluated the correlation of mRNA and
      protein levels in two hematopoietic cell lines representing distinct stages of
      myeloid differentiation, as well as in the livers of mice treated for different
      periods of time with three different peroxisome proliferative activated receptor
      agonists. We observe that the differential expression of mRNA (up or down) can
      capture at most 40% of the variation of protein expression. Although the overall
      pattern of protein expression is similar to that of mRNA expression, the
      incongruent expression between mRNAs and proteins emphasize the importance of
      posttranscriptional regulatory mechanisms in cellular development or perturbation
      that can be unveiled only through integrated analyses of both proteins and mRNAs.

PMID- 15238603
TI  - Inactivation of c-Cbl reverses neonatal lethality and T cell developmental arrest
      of SLP-76-deficient mice.
AB  - c-Cbl is an adaptor protein that negatively regulates signal transduction events
      involved in thymic-positive selection. To further characterize the function of c
      Cbl in T cell development, we analyzed the effect of c-Cbl inactivation in mice
      deficient in the scaffolding molecule SLP-76. SLP-76-deficient mice show a high
      frequency of neonatal lethality; and in surviving mice, T cell development is
      blocked at the DN3 stage. Inactivation of c-cbl completely reversed the neonatal
      lethality seen in SLP-76-deficient mice and partially reversed the T cell
      development arrest in these mice. SLP-76(-/-) Cbl(-/-) mice exhibited marked
      expansion of polarized T helper type (Th)1 and Th2 cell peripheral CD4(+) T
      cells, lymphoid infiltrates of parenchymal organs, and premature death. This
      rescue of T cell development is T cell receptor dependent because it does not
      occur in recombination activating gene 2(-/-) SLP-76(-/-) Cbl(-/-) triple
      knockout mice. Analysis of the signal transduction properties of SLP-76(-/-) Cbl(
      /-) T cells reveals a novel SLP-76- and linker for activation of T cells
      independent pathway of extracellular signal-regulated kinase activation, which is
      normally down-regulated by c-Cbl.

PMID- 15238604
TI  - Examination of Msh6- and Msh3-deficient mice in class switching reveals
      overlapping and distinct roles of MutS homologues in antibody diversification.
AB  - Somatic hypermutation and class switch recombination (CSR) contribute to the
      somatic diversification of antibodies. It has been shown that MutS homologue
      (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base
      substitutions in somatic hypermutation. However, their roles in CSR have not yet
      been reported. Here we show that Msh6(-)(/)(-) mice have a decrease in CSR,
      whereas Msh3(-)(/)(-) mice do not. When switch regions were analyzed for
      mutations, deficiency in Msh6 was associated with an increase in transition
      mutations at G/C basepairs, mutations at RGYW/WRCY hotspots, and a small increase
      in the targeting of G/C bases. In addition, Msh6(-)(/)(-) mice exhibited an
      increase in the targeting of recombination sites to GAGCT/GGGGT consensus repeats
      and hotspots in Sgamma3 but not in Smicro. In contrast to Msh2(-)(/)(-) mice,
      deficiency in Msh6 surprisingly did not change the characteristics of Smicro
      Sgamma3 switch junctions. However, Msh6(-)(/)(-) mice exhibited a change in the
      positioning of Smicro and Sgamma3 junctions. Although none of these changes were
      seen in Msh3(-)(/)(-) mice, they had a higher percentage of large inserts in
      their switch junctions. Together, our data suggest that MutS homologues Msh2,
      Msh3, and Msh6 play overlapping and distinct roles during antibody
      diversification processes.

PMID- 15238605
TI  - A role for Msh6 but not Msh3 in somatic hypermutation and class switch
      recombination.
AB  - Somatic hypermutation is initiated by activation-induced cytidine deaminase
      (AID), and occurs in several kilobases of DNA around rearranged immunoglobulin
      variable (V) genes and switch (S) sites before constant genes. AID deaminates
      cytosine to uracil, which can produce mutations of C:G nucleotide pairs, and the
      mismatch repair protein Msh2 participates in generating substitutions of
      downstream A:T pairs. Msh2 is always found as a heterodimer with either Msh3 or
      Msh6, so it is important to know which one is involved. Therefore, we sequenced V
      and S regions from Msh3- and Msh6-deficient mice and compared mutations to those
      from wild-type mice. Msh6-deficient mice had fewer substitutions of A and T bases
      in both regions and reduced heavy chain class switching, whereas Msh3-deficient
      mice had normal antibody responses. This establishes a role for the Msh2-Msh6
      heterodimer in hypermutation and switch recombination. When the positions of
      mutation were mapped, several focused peaks were found in Msh6(-/-) clones,
      whereas mutations were dispersed in Msh3(-/-) and wild-type clones. The peaks
      occurred at either G or C in WGCW motifs (W = A or T), indicating that C was
      mutated on both DNA strands. This suggests that AID has limited entry points into
      V and S regions in vivo, and subsequent mutation requires Msh2-Msh6 and DNA
      polymerase.

PMID- 15238606
TI  - 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin
      inhibits acute inflammation.
AB  - The established model for the mechanism of action of aspirin is the inhibition of
      prostaglandin synthesis. However, this has never fully explained aspirin's
      repertoire of antiinflammatory properties. We found in acute pleuritis that
      aspirin, but not salicylate, indomethacin, or piroxicam, increased plasma nitric
      oxide (NO), which correlated with a reduction in inflammation. Inhibiting aspirin
      elicited NO pharmacologically in this model nullified the antiinflammatory
      effects of aspirin. Moreover, aspirin was not antiinflammatory in either
      constitutive (eNOS) or inducible NO synthase (iNOS) knockout mice with IL-1beta
      induced peritonitis. It transpires that aspirin generates NO through its unique
      ability to trigger the synthesis of 15-epi-lipoxin A(4). Aspirin and 15-epi
      lipoxin A(4) were shown to inhibit leukocyte trafficking in an NO-dependent
      manner using intravital microscopy on IL-1beta-stimulated mouse mesentery. Not
      only did aspirin inhibit leukocyte-endothelial interaction in a manner similar to
      NO in wild-type mice but both aspirin and 15-epi-lipoxin A(4) had markedly
      reduced effects on leukocyte-endothelial cell adherence in eNOS- and iNOS
      deficient mice compared with wild type. Collectively, these data suggest that
      aspirin triggers the synthesis of 15-epi-lipoxin A(4), which increases NO
      synthesis through eNOS and iNOS. This aspirin-elicited NO exerts antiinflammatory
      effects in the microcirculation by inhibiting leukocyte-endothelium interactions.

PMID- 15238608
TI  - Essential role of lung plasmacytoid dendritic cells in preventing asthmatic
      reactions to harmless inhaled antigen.
AB  - Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper
      (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells
      (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and
      plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an
      immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion
      of pDCs during inhalation of normally inert antigen led to immunoglobulin E
      sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell
      cytokine production, cardinal features of asthma. Furthermore, adoptive transfer
      of pDCs before sensitization prevented disease in a mouse asthma model. On a
      functional level, pDCs did not induce T cell division but suppressed the
      generation of effector T cells induced by mDCs. These studies show that pDCs
      provide intrinsic protection against inflammatory responses to harmless antigen.
      Therapies exploiting pDC function might be clinically effective in preventing the
      development of asthma.

PMID- 15238607
TI  - Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune
      encephalomyelitis.
AB  - The transcription factors signal transducer and activator of transcription
      (STAT)1 and T-bet control the differentiation of interferon (IFN)-gamma-producing
      T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the
      initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a
      disease initiated by Th1 cells. T-bet-deficient mice immunized with myelin
      oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This
      protection was also observed when T-bet(-/-) mice were crossed to the MOG
      specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is
      downstream of STAT1, STAT1(-/-) mice were highly susceptible to EAE and developed
      more severe and accelerated disease with atypical neuropathologic features. The
      function of T-bet was dominant as mice deficient in both T-bet and STAT1 were
      also protected from EAE. CD4(+) CD25(+) regulatory T cells from these two mice
      strains were fully competent and do not explain the difference in disease
      susceptibility. However, enhanced EAE in STAT1(-/-) mice was associated with
      continued generation of IFN-gamma-producing Th1 cells and up-regulation of
      selective chemokines responsible for the increased recruitment of macrophages and
      neutrophils in the central nervous system. Although the two transcription
      factors, STAT1 and T-bet, both induce IFN-gamma gene transcription, our results
      demonstrate marked differences in their function in regulating pathogenic Th1
      cell responses.

PMID- 15238609
TI  - Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the
      brain.
AB  - Streptococcus pneumoniae is the most common cause of bacterial meningitis of high
      mortality and morbidity. Neurological sequelae include paralysis, mental
      retardation, and learning disorders. In humans, neurons of the hippocampus
      undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an
      essential component of mammalian cell membranes and PtdCho deficiency, either due
      to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal
      neurons. We show that apoptosis of a variety of brain cells after pneumococcal
      infection arises from inhibition of PtdCho biosynthesis, the first such activity
      described for a bacterium. Apoptosis inhibitors did not prevent the bacterial
      dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso
      phosphatidylcholine prevents cell death and treatment of mice with cytidine
      diphosphocholine attenuates hippocampal damage during meningitis, even after the
      onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis
      activates an apoptotic cascade that is a causative event in pathogenesis and
      amenable to therapeutic intervention.

PMID- 15238617
TI  - Genetic kininogen deficiency contributes to aortic aneurysm formation but not to
      atherosclerosis.
AB  - Brown Norway (BN) and BN Katholiek (BN/Ka) rat strains are both susceptible to
      develop lesions in the internal elastic lamina (IEL) of the aorta. BN/Ka rats are
      characterized by a single point mutation in the kininogen gene leading to
      deficiency in high- and low-molecular-weight kininogen. Recently, a suggestive
      quantitative trait locus for lesions in the IEL of the abdominal aorta was
      identified in an F2 intercross between Dahl salt-sensitive (SS) and BN rats,
      implicating kininogen as a positional candidate gene. Therefore, BN and BN/Ka rat
      strains represent ideal model organisms with which to study the contribution of
      kininogen to the genetic predisposition to IEL lesion formation and to
      characterize the early events underlying vascular remodeling. Here we present
      data demonstrating that genetic kininogen deficiency promotes the formation of
      aneurysms in the abdominal aorta but not the development of atherosclerosis upon
      12-wk treatment with an atherogenic diet. Aneurysm formation was associated with
      an enhanced elastolysis, increased expression of MMP-2 and MMP-3, downregulation
      of TIMP-4, and with FasL- and caspase-3-mediated apoptosis. Kininogen-deficient
      animals also featured changes in plasma cytokines compatible with apoptotic
      vascular damage, i.e., upregulation of IFN-gamma and downregulation of GM-CSF and
      IL-1beta. Finally, in response to atherogenic diet, kininogen-deficient animals
      developed an increase in HDL/total cholesterol index, pronounced fatty liver and
      heart degeneration, and lipid depositions in aortic media without atherosclerotic
      plaque formation. These findings suggest that genetic kininogen deficiency
      renders vascular tissue prone to aneurysmatic but not to atherosclerotic lesions.

PMID- 15238618
TI  - Plasticity of mouse renal collecting duct in response to potassium depletion.
AB  - Plasticity of mouse renal collecting duct in response to potassium depletion.-
      Renal collecting ducts are the main sites for regulation of whole body potassium
      balance. Changes in dietary intake of potassium induce pleiotropic adaptations of
      collecting duct cells, which include alterations of ion and water transport
      properties along with an hypertrophic response. To study the pleiotropic
      adaptation of the outer medullary collecting duct (OMCD) to dietary potassium
      depletion, we combined functional studies of renal function (ion, water, and
      acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and
      hyperplasia (PCNA labeling), and large scale analysis of gene expression
      (transcriptome analysis). The transcriptome of OMCD was compared in mice fed
      either a normal or a potassium-depleted diet for 3 days using serial analysis of
      gene expression (SAGE) adapted for downsized extracts. SAGE is based on the
      generation of transcript-specific tag libraries. Approximately 20,000 tags
      corresponding to 10,000 different molecular species were sequenced in each
      library. Among the 186 tags differentially expressed (P < 0.05) between the two
      libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression
      profile obtained in the control library was representative of different
      functional classes of proteins and of the two cell types (principal and alpha
      intercalated cells) constituting the OMCD. Combined with gene expression
      analysis, results of functional and morphological studies allowed us to identify
      candidate genes for distinct physiological processes modified by potassium
      depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy.
      Finally, comparison of mouse and human OMCD transcriptomes allowed us to address
      the question of the relevance of the mouse as a model for human physiology and
      pathophysiology.

PMID- 15238619
TI  - Liver gene expression associated with diet and lesion development in
      atherosclerosis-prone mice: induction of components of alternative complement
      pathway.
AB  - Diet-induced changes in serum lipoproteins are a major risk factor for the
      development of atherosclerosis, the leading cause of mortality in Westernized
      countries. Atherosclerosis is now appreciated to be a systemic inflammatory
      disease where increased synthesis of inducible proteins by the liver, such as C
      reactive protein (CRP) and others, may play roles in accelerating the disease
      process. To systematically investigate the genetic response of the liver to diet
      induced atherosclerosis, we applied high-density microarray technology in a mouse
      model of atherosclerosis (LDLR-/- mouse). LDLR-/- mice and congenic (LDLR+/+)
      controls were placed on low-fat (LF) or high-fat (HF) Western-style diets. The
      Western diet produced sustained elevations in total cholesterol (2.5-fold for
      LDLR+/+, 5.0-fold LDLR-/-) relative to the respective LF groups. Tissues were
      harvested after 12 wk when significant atherosclerotic lesion development was
      first detectable by en face histomorphometry of oil red O-stained aortas. Diet,
      rather than genotype, was most highly associated with development of
      atherosclerotic lesions. Liver mRNA expression profiles of triplicate animals
      from each group were determined by high-density oligonucleotide microarrays; and
      genes with transcript levels influenced by genotype and diet were identified by
      two-way ANOVA. Approximately one-third of the 102 genes identified to be altered
      by diet [Pr(F) < 0.0005] were involved in lipid metabolism. In addition, we
      identified components of the alternative complement pathway, including C3,
      properdin, and factor D, for which mRNA levels were independently confirmed by
      quantitative real-time RT-PCR analysis, and C3 protein was demonstrated in aortic
      lesions by immunostaining. These findings suggest that induction of the
      alternative complement pathway may be an additional mechanism by which a high
      fat/Western diet accelerates atherosclerosis.

PMID- 15238620
TI  - Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and
      thrombin inhibitor management testing.
AB  - BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be
      acutely anticoagulated with direct thrombin inhibitors (DTIs). The
      anticoagulation is typically monitored using the activated partial thromboplastin
      time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for
      measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in
      samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to
      achieve low (0.1-1.2 microg/mL) and high (1.5-8.0 microg/mL) drug concentrations.
      Each low-concentration DTI sample was tested using all aPTT reagents, while each
      low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All
      aPTT reagents had a significant dose-dependent correlation with drug
      concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios
      obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to
      argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1
      to 1.2 microg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most
      sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5
      seconds, respectively, at 1.2 microg/mL of drug. Pathromtin was the most
      sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2
      microg/mL of drug. There was no statistically significant difference between the
      TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM
      clotting times were equivalent. CONCLUSIONS: There are unique differences between
      reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT
      monitoring of DTI anticoagulation include the ECT and TIM.

PMID- 15238621
TI  - Medication adherence and associated hemoglobin A1c in type 2 diabetes.
AB  - BACKGROUND: Tight blood glucose control has been correlated with a reduction in
      diabetes complications. Adherence to antidiabetic medications is crucial to
      achieving blood glucose control. OBJECTIVE: To assess the relationship between
      good glucose control [glycosylated hemoglobin (HbA1c) levels] and adherence to
      prescribed treatment in patients on a stable medication regimen for type 2
      diabetes. METHODS: The Morisky survey, a 4-item questionnaire that predicts
      patient medication-taking behavior, was used to assess adherence in 301 patients.
      The relationship of HbA1c to Morisky score was evaluated, controlling for other
      variables related to patient demographics and clinical characteristics. Data were
      analyzed using a general linear model on log (HbA1c). RESULTS: Unadjusted mean
      HbA1c values (capped at 14.0%) for patients with Morisky scores of 0 or 1, 2, 3,
      and 4 were 8.92%, 8.67%, 7.74%, and 7.60%, respectively. Of all patients, 13.0%,
      14.0%, 24.3%, and 48.8% had scores of 0 or 1, 2, 3, and 4, respectively. Good
      adherence (Morisky score > or = 3) was associated with a 10% lower total HbA1c (p
      = 0.0003) adjusted for all other factors in the model. Duration of diabetes (5-10
      y) and presence of diabetes complications were also significantly associated with
      HbA1c (p = 0.026 and 0.002, respectively). Adherence was poor in 27% of patients.
      CONCLUSIONS: This study found that patients with a higher score on the Morisky
      scale had a lower associated HbA1c measurement. The Morisky score may be an
      efficient tool for identifying patients with poor medication-taking behavior who
      can then be targeted for directed adherence counseling services.

PMID- 15238622
TI  - Self-reported Morisky score for identifying nonadherence with cardiovascular
      medications.
AB  - BACKGROUND: The Morisky medication adherence scale is a commonly used adherence
      screening tool. It is composed of 4 yes/no questions about past medication use
      patterns and is thus quick and simple to use during drug history interviews.
      OBJECTIVE: To evaluate the use of the self-reported Morisky score as a screening
      tool for identifying patients who have been nonadherent with chronic
      cardiovascular medications. METHODS: Patients who had taken an angiotensin
      converting enzyme inhibitor or lipid-lowering agent for at least 3 consecutive
      months were interviewed using a structured questionnaire including the Morisky
      scale. Nonadherence was defined as taking < 80% of chronic cardiovascular
      medications based on prescription refill data over the previous 14 months.
      RESULTS: Forty-nine of 377 (13%) patients were categorized as nonadherent;
      however, only 12 (3%) patients had Morisky scores suggesting a high likelihood of
      nonadherence (3 or 4). While the Morisky score was a significant independent
      predictor of nonadherence by multivariate analysis, there was no threshold score
      or individual question that yielded concurrent high sensitivity and positive
      predictive values (PPVs) for identifying nonadherent patients. The internal
      consistency of the questions was low (alpha 0.32), as were item-to-total score
      correlations, suggesting that the individual questions were not measuring the
      same attribute. CONCLUSIONS: Using the Morisky scale to identify patients who
      have been nonadherent with chronic cardiovascular medications may be reasonable
      in some settings; however, the threshold score would have to be chosen based on a
      trade-off between sensitivity and PPV. These results were likely influenced by
      the low rate of nonadherence in this cohort. Rewording the questions, increasing
      the number of questions, and the use of graded response options may improve
      consistency.

PMID- 15238623
TI  - Twin-twin transfusion--as good as it gets?

PMID- 15238624
TI  - Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin
      transfusion syndrome.
AB  - BACKGROUND: Monochorionic twin pregnancies complicated by severe twin-to-twin
      transfusion syndrome at midgestation can be treated by either serial
      amnioreduction (removal of large volumes of amniotic fluid) or selective
      fetoscopic laser coagulation of the communicating vessels on the chorionic plate.
      We conducted a randomized trial to compare the efficacy and safety of these two
      treatments. METHODS: Pregnant women with severe twin-to-twin transfusion syndrome
      before 26 weeks of gestation were randomly assigned to laser therapy or
      amnioreduction. We assessed perinatal survival of at least one twin (a
      prespecified primary outcome), survival of at least one twin at six months of
      age, and survival without neurologic complications at six months of age on the
      basis of the number of pregnancies or the number of fetuses or infants, as
      appropriate. RESULTS: The study was concluded early, after 72 women had been
      assigned to the laser group and 70 to the amnioreduction group, because a planned
      interim analysis demonstrated a significant benefit in the laser group. As
      compared with the amnioreduction group, the laser group had a higher likelihood
      of the survival of at least one twin to 28 days of age (76 percent vs. 56
      percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence
      interval, 0.25 to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the
      laser group also had a lower incidence of cystic periventricular leukomalacia (6
      percent vs. 14 percent, P=0.02) and were more likely to be free of neurologic
      complications at six months of age (52 percent vs. 31 percent, P=0.003).
      CONCLUSIONS: Endoscopic laser coagulation of anastomoses is a more effective
      first-line treatment than serial amnioreduction for severe twin-to-twin
      transfusion syndrome diagnosed before 26 weeks of gestation.

PMID- 15238625
TI  - Wasting, but not malnutrition, predicts cardiovascular mortality in end-stage
      renal disease.

PMID- 15238626
TI  - Prevention of glomerular crescent formation in glomerulonephritis by
      mycophenolate mofetil in rats.
AB  - BACKGROUND: Glomerular crescent formation is a prominent feature of aggressive
      forms of glomerulonephritis (GN) and is associated with a poor prognosis. We
      investigated whether the potent immunosuppressive agent mycophenolate mofetil
      (MMF) could prevent crescent formation in a model of anti-glomerular basement
      membrane (GBM) GN in the rat. METHODS: GN with glomerular crescents was induced
      by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The
      experimental rats were divided into two groups: rats received vehicle (0.5%
      carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and
      the urine and blood samples were evaluated. The rats were sacrificed at day 14,
      and histological analysis was performed. The mRNA expression of cytokines and
      adhesion molecules in the kidney was analysed by reverse transcription-polymerase
      chain reaction (RT-PCR). RESULTS: Marked proteinuria, glomerular crescent
      formation and glomerulosclerosis were observed in this model, and these were
      significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell
      infiltration was also observed, and MMF treatment significantly inhibited
      macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis
      revealed that mRNA and protein expression of osteopontin was decreased by the
      treatment with MMF. In addition, MMF treatment in the early stages of GN could
      inhibit proteinuria, glomerular crescent formation and glomerulosclerosis.
      CONCLUSIONS: These findings suggest therapeutic potential for MMF in the
      inhibition of glomerular crescent formation in GN and provide new insights into
      the mechanism underlying the amelioration of crescentic GN by MMF treatment.

PMID- 15238627
TI  - Nail fold videocapillaroscopy in mixed cryoglobulinaemia.
AB  - BACKGROUND: Nail fold videocapillaroscopy (NVC) has been extensively used to
      examine morphological and functional changes of microcirculation in connective
      tissue diseases. The nutritional circulation that depends on tissue capillaries,
      can be expected to be significantly impacted in mixed cryoglobulinaemia (MC).
      METHODS: Using NVC, we evaluated 29 patients with MC (19 women), mean age 66
      years (range 40-83). They included 28 hepatitis C virus (HCV) positive patients
      14 genotype 1b, 10 genotype 2a 2c, two genotype 4, two with undetermined
      genotype. Of them, 18 had type II (IgMk-IgG) MC and 11 had type III. All patients
      were symptomatic, presenting with weakness (24 of 29 patients), arthralgia (24),
      purpura (16), peripheral neuropathy (20), Raynaud's phenomenon (8), hypertension
      (19) and membranoproliferative glomerulonephritis (MPGN) (9). The nail fold
      capillaries of four fingers per hand were examined using a videomicroscope.
      RESULTS: Of the 29 patients, 27 had morphological abnormalities (including
      tortuosity and apical enlargement), 18 had capillaries with deeply altered
      orientations, 17 had shortened capillaries and 20 neoangiogenetic phenomena.
      These four types of capillary abnormalities were simultaneously present in 10,
      suggesting this combination to be a characteristic pattern in MC. Less common
      alterations included haemorrhages (10 cases), enlarged and giant capillaries (2)
      and avascular areas (2). The patients with MC-associated MPGN had a significantly
      greater number of capillary abnormalities (mean 4.5, range 4-6) than non
      nephritic patients (mean 3.5, range 1-6, P = 0.01). The number of capillary
      abnormalities was not related to the presence of Raynaud's phenomenon.
      Microcirculatory changes did not correlate with other clinical manifestations or
      serological indices, including cryocrit, cryoglobulin type, HCV genotype, viral
      load, haemoglobin, ALT, rheumatoid factor, IgM and C4 levels. CONCLUSIONS:
      Patients with MC show a variety of microcirculatory changes, often clustered in a
      characteristic pattern of abnormally oriented, short capillaries and
      neoangiogenetic phenomena. Capillary changes are more numerous in nephritic
      patients.

PMID- 15238628
TI  - Amelioration of myoglobinuric renal damage in rats by chronic exposure to
      flavonol-rich red wine.
AB  - BACKGROUND: Myoglobinuric acute renal failure causes increased oxidative stress.
      Since ethanol upregulates renal antioxidant enzymes and wine polyphenols behave
      as antioxidants, we tested the hypothesis that red wine components would
      ameliorate the renal damage caused by rhabdomyolysis. METHODS: Adult rats
      received water (control), alcohol-free red wine, ethanol 12.5% (v/v) or red wine
      for 10 weeks. Rhabdomyolysis was induced by glycerol injection (50%, 10 ml/kg,
      i.m.), and urine and blood samples were collected 6 h later to measure renal
      function parameters, creatine kinase (CK) activity, free F(2)-isoprostanes and
      total antioxidant capacity. Kidneys were then harvested for morphological studies
      and determinations of lipid peroxidation, protein carbonylation, (Na + K)-ATPase
      and antioxidant enzyme activities. RESULTS: In the control group, myoglobinuria
      was associated with a 68% decrease in creatinine clearance and increases in
      plasma creatinine and blood urea nitrogen of 3.2 and 1.8 times above baseline,
      respectively. Controls also showed increases in plasma free F(2)-isoprostanes
      levels and CK activity, together with enhanced renal expression of the
      antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase, as
      well as increased production of malondialdehyde and carbonyls. Rhabdomolysis
      reduced renal (Na + K)-ATPase activity and this reduction was associated with a 5
      fold increase in fractional sodium excretion as well as morphological damage to
      the kidney. These changes were significantly attenuated by pretreatment with
      chronic red wine exposure prior to glycerol injection. A less marked degree of
      functional and biochemical protection was also observed in response to the
      administration of alcohol-free red wine and ethanol. CONCLUSIONS: The present
      data suggest that red wine protects against functional, biochemical and
      morphological damage caused by rhabdomyolysis in the rat, and this protection may
      be due to the synergistic effects of ethanol and non-alcoholic red wine
      components.

PMID- 15238629
TI  - Angiotensin II activates the human renin promoter in an in vitro model: the role
      of c-Jun-N-terminal kinase.
AB  - BACKGROUND: Angiotensin II (Ang II) down-regulates renin expression in
      juxtaglomerular cells, however, recent experimental evidence obtained in
      transgenic mice suggested that Ang II may "paradoxically" increase
      transcriptional activity of the proximal renin promoter. METHODS: To dissect
      signalling mechanisms contributing to the up-regulation of the proximal renin
      promoter by Ang II, porcine proximal tubular cells stably expressing the rabbit
      AT(1) receptor (LLC-PK/AT(1)) were transiently transfected with a luciferase
      reporter construct containing the 582 bp long piece of the human renin promoter.
      Activation of mitogen-activated protein kinases (MAPK) was detected by western
      blotting using phospho-MAPK-specific antibodies. RESULTS: Ang II dose-dependently
      stimulated the transcriptional activity of the human renin promoter (10(-7) M Ang
      II: 3.50+/-1.25-fold stimulation). In these cells Ang II activated both
      extracellular signal-regulated kinase (ERK) and the c-Jun-N-terminal kinase
      (JNK). Inhibition of the ERK cascade did not reduce the stimulation of the renin
      promoter by Ang II, however, two expression vectors designed to inhibit the JNK
      pathway, the dominant negative JNK and the Jun-kinase interacting peptide
      inhibited the fold stimulation induced by Ang II (2.75+/-0.69 vs 1.6+/-0.23 and
      1.8+/-0.34, respectively; P<0.01). Furthermore, genistein, a tyrosine kinase
      inhibitor, blocked the effect of Ang II both on the JNK and the promoter
      activation. CONCLUSION: Ang II may have a stimulatory effect on the proximal
      renin promoter in proximal tubular cells and this effect is mediated by tyrosine
      kinases and the JNK cascade.

PMID- 15238630
TI  - Hypertension in HIV-1-infected patients and its impact on renal and
      cardiovascular integrity.
AB  - BACKGROUND: With increasing life spans of HIV-infected individuals under highly
      active antiretroviral therapy, long-term consequences of the chronic infection
      and antiretroviral treatment are becoming more prevalent. Data on prevalence and
      consequences of hypertension are limited, but recent studies suggest that HIV
      infected individuals are at a higher risk of developing hypertension. METHODS: In
      this prospective study, HIV-1-infected patients from the Frankfurt AIDS Cohort
      Study (FACS) were followed for 1 year to determine the frequency of systemic
      hypertension and to assess the associated clinical and demographic factors.
      RESULTS: A total 214 HIV-1-infected patients, predominantly Caucasian males,
      participated in the study. Prevalence of systemic hypertension was 29%. The
      groups of hypertensive and normotensive individuals were comparable in terms of
      ethnic background and duration of infection. As in the general population,
      hypertensive subjects were older (49.1+/-11.1 vs 39.0+/-8.1 years; P<0.0001) and
      waist-to-hip ratio was higher than in normotensive individuals (0.99+/-0.07 vs
      0.93+/-0.08; P<0.0001). Hypertension was associated with a much higher frequency
      of persistent proteinuria (41.1% vs 2.8%; P<0.001), coronary heart disease (16.1%
      vs 1.3%; P<0.0001) and myocardial infarction (8.1% vs 0.7%; P<0.005), whereas
      most cardiovascular risk factors were similar in both groups. CONCLUSIONS: Our
      data do not demonstrate any association between the presence of hypertension and
      antiretroviral therapy or immune status. However, hypertension seems to have a
      high impact on the existing risk for premature cardiovascular disease.
      Furthermore, overt proteinuria is frequent in HIV-1 infection with hypertension
      and might be due to hypertensive nephrosclerosis as well as yet undefined renal
      disease in these patients.

PMID- 15238631
TI  - Concomitant administration of cyclosporine and ketoconazole in idiopathic
      nephrotic syndrome.
AB  - BACKGROUND: The deliberate use of ketoconazole to reduce the need for
      cyclosporine (CsA) is not new, but it is particularly relevant because of the
      high cost of CsA. Many studies have documented this benefit in renal and cardiac
      transplants, but this co-administration has not been reported in patients with
      nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic
      patients who were steroid resistant, dependent or frequent relapsers and received
      CsA therapy. Among these patients 153 received daily ketoconazole therapy in a
      dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54
      patients received CsA alone. The majority of our cases were children (179 were
      below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority
      of the study population received the drugs for 1-2 years. Patients who received
      CsA and ketoconazole were comparable with those who received CsA alone regarding
      age, sex, duration of renal disease, renal pathology, severity of nephrotic
      syndrome, renal function, hepatic function and steroid response. Co
      administration of ketoconazole significantly reduced mean doses of CsA by 37%
      after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic
      functions remained within the normal range in both groups. Additionally, co
      administration of ketoconazole significantly improved the response to CsA
      therapy, successful steroid withdrawal and decreased the frequency of renal
      impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic
      nephrotic patients significantly reduces CsA costs and may improve its response.

PMID- 15238632
TI  - Evolutionary trace analysis of the alpha-D-phosphohexomutase superfamily.
AB  - The alpha-D-phosphohexomutase superfamily is composed of four related enzymes
      that catalyze a reversible, intramolecular phosphoryl transfer on their sugar
      substrates. The enzymes in this superfamily play important and diverse roles in
      carbohydrate metabolism in organisms from bacteria to humans. Recent structural
      and mechanistic studies of one member of this superfamily,
      phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa, have
      provided new insights into enzyme mechanism and substrate recognition. Here we
      use sequence-sequence and sequence-structure comparisons via evolutionary trace
      analysis to examine 71 members of the alpha-D-phosphohexomutase superfamily.
      These analyses show that key residues in the active site, including many of those
      involved in substrate contacts in the P. aeruginosa PMM/PGM complexes, are
      conserved throughout the enzyme family. Several important regions show class
      specific differences in sequence that appear to be correlated with differences in
      substrate specificity exhibited by subgroups of the family. In addition, we
      describe the translocation of a 20-residue segment containing the catalytic
      phosphoserine of phosphoacetylglucosamine mutase, which uniquely identifies
      members of this subgroup.

PMID- 15238633
TI  - Solution NMR structure of the C-terminal domain of the human protein DEK.
AB  - The chromatin-associated protein DEK was first identified as a fusion protein in
      patients with a subtype of acute myelogenous leukemia. It has since become
      associated with diverse human ailments ranging from cancers to autoimmune
      diseases. Despite much research effort, the biochemical basis for these clinical
      connections has yet to be explained. We have identified a structural domain in
      the C-terminal region of DEK [DEK(309-375)]. DEK(309-375) implies clinical
      importance because it can reverse the characteristic abnormal DNA-mutagen
      sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. We
      determined the solution structure of DEK(309-375) by nuclear magnetic resonance
      spectroscopy, and found it to be structurally homologous to the E2F/DP
      transcription factor family. On the basis of this homology, we tested whether
      DEK(309-375) could bind DNA and identified the DNA-interacting surface. DEK
      presents a hydrophobic surface on the side opposite the DNA-interacting surface.
      The structure of the C-terminal region of DEK provides insights into the protein
      function of DEK.

PMID- 15238634
TI  - A mobile loop order-disorder transition modulates the speed of chaperonin
      cycling.
AB  - Molecular machines order and disorder polypeptides as they form and dissolve
      large intermolecular interfaces, but the biological significance of coupled
      ordering and binding has been established in few, if any, macromolecular systems.
      The ordering and binding of GroES co-chaperonin mobile loops accompany an ATP
      dependent conformational change in the GroEL chaperonin that promotes client
      protein folding. Following ATP hydrolysis, disordering of the mobile loops
      accompanies co-chaperonin dissociation, reversal of the GroEL conformational
      change, and release of the client protein. "High-affinity" GroEL mutants were
      identified by their compatibility with "low-affinity" co-chaperonin mutants and
      incompatibility with high-affinity co-chaperonin mutants. Analysis of binding
      kinetics using the intrinsic fluorescence of tryptophan-containing co-chaperonin
      variants revealed that excessive affinity causes the chaperonin to stall in a
      conformation that forms in the presence of ATP. Destabilizing the beta-hairpins
      formed by the mobile loops restores the normal rate of dissociation. Thus, the
      free energy of mobile-loop ordering and disordering acts like the inertia of an
      engine's flywheel by modulating the speed of chaperonin conformational changes.

PMID- 15238635
TI  - H-bonding in protein hydration revisited.
AB  - H-bonding between protein surface polar/charged groups and water is one of the
      key factors of protein hydration. Here, we introduce an Accessible Surface Area
      (ASA) model for computationally efficient estimation of a free energy of water
      protein H-bonding at any given protein conformation. The free energy of water
      protein H-bonds is estimated using empirical formulas describing probabilities of
      hydrogen bond formation that were derived from molecular dynamics simulations of
      water molecules at the surface of a small protein, Crambin, from the Abyssinian
      cabbage (Crambe abyssinica) seed. The results suggest that atomic solvation
      parameters (ASP) widely used in continuum hydration models might be dependent on
      ASA for polar/charged atoms under consideration. The predictions of the model are
      found to be in qualitative agreement with the available experimental data on
      model compounds. This model combines the computational speed of ASA potential,
      with the high resolution of more sophisticated solvation methods.

PMID- 15238637
TI  - Biophysical characterization of Z(SPA-1)--a phage-display selected binder to
      protein A.
AB  - Affibodies are a novel class of binding proteins selected from phagemid libraries
      of the Z domain from staphylococcal protein A. The Z(SPA-1) affibody was selected
      as a binder to protein A, and it binds the parental Z domain with micromolar
      affinity. In earlier work we determined the structure of the Z:Z(SPA-1) complex
      and noted that Z(SPA-1) in the free state exhibits several properties
      characteristic of a molten globule. Here we present a more detailed biophysical
      investigation of Z(SPA-1) and four Z(SPA-1) mutants with the objective to
      understand these properties. The characterization includes thermal and chemical
      denaturation profiles, ANS binding assays, size exclusion chromatography,
      isothermal titration calorimetry, and an investigation of structure and dynamics
      by NMR. The NMR characterization of Z(SPA-1) was facilitated by the finding that
      trimethylamine N-oxide (TMAO) stabilizes the molten globule conformation in favor
      of the fully unfolded state. All data taken together lead us to conclude the
      following: (1) The topology of the molten globule conformation of free Z(SPA-1)
      is similar to that of the fully folded structure in the Z-bound state; (2) the
      extensive mutations in helices 1 and 2 destabilize these without affecting the
      intrinsic stability of helix 3; (3) stabilization and reduced aggregation can be
      achieved by replacing mutated residues in Z(SPA-1) with the corresponding wild
      type Z residues. This stabilization is better correlated to changes in helix
      propensity than to an expected increase in polar versus nonpolar surface area of
      the fully folded state.

PMID- 15238636
TI  - In vivo folding of recombinant metallo-beta-lactamase L1 requires the presence of
      Zn(II).
AB  - Metallo-beta-lactamase L1, secreted by pathogenic Stenotrophomonas maltophilia,
      is a dinuclear Zn(II)-containing enzyme that hydrolyzes almost all known
      penicillins, cephalosporins, and carbapenems. The presence of Zn(II) ions in both
      metal binding sites is essential for full enzymatic activity; however, the
      mechanism of physiological metal incorporation is unknown. To probe metal
      incorporation, L1 was over-expressed in minimal media with (mmL1+Zn) and without
      (mmL1-Zn) Zn(II) added to the media, and the resulting proteins were purified and
      characterized. The mmL1+Zn sample was bound by a Q-Sepharose column, exhibited
      steady-state kinetic properties, bound Zn(II), existed as a tetramer, and yielded
      fluorescence emission and CD spectra similar to L1 overexpressed in rich media.
      On the other hand, the mmL1-Zn sample did not bind to a Q-Sepharose column, and
      gel filtration studies demonstrated that this protein was monomeric. The mmL1-Zn
      sample exhibited a lower kcat value, bound less Zn(II), and yielded fluorescence
      emission and CD spectra consistent with this enzyme being folded improperly.
      Taken together, these data demonstrate that the proper folding of L1 requires the
      presence of Zn(II) and suggest that in vitro, thermodynamic metal binding studies
      do not accurately reflect physiological metal incorporation into L1.

PMID- 15238638
TI  - Modeling and simulation of the human delta opioid receptor.
AB  - A model for the human delta opioid receptor has been generated via sequence
      alignment, structure building using the crystal structure of bovine rhodopsin as
      a template, and refinement by molecular dynamics simulation. The model building
      suggested that, in addition to the previously postulated interaction between D128
      and Y308, an internal salt bridge also exists between residues D128 and R192,
      both of which are conserved in all the opioid receptors. The model and salt
      bridge were then shown to be stable during a 20-nsec simulation in a lipid
      bilayer. It is therefore proposed that both of these interactions play a role in
      stabilizing the inactive state of the receptor. The model is also used in an
      effort to rationalize many of the mutational studies performed on delta opioid
      receptors, and to suggest a plausible explanation for the differences between
      known delta opioid agonists and antagonists.

PMID- 15238639
TI  - Cation-pi interactions studied in a model coiled-coil peptide.
AB  - Cation-pi interactions between aromatic amino acids and the positively charged
      residues lysine and arginine have been proposed to play an important role in
      stabilizing protein structure. We have used a peptide that adopts a coiled coil
      structure as a model system to evaluate the energetic contribution of cation-pi
      interactions to protein folding. Peptides were designed in which phenylalanine,
      tyrosine, and tryptophan were placed at a solvent-exposed position of the helix,
      one turn removed from an arginine residue that could provide a favorable cation
      pi interaction. Only the arginine-phenylalanine pairing provided significant
      stabilization of the peptide structure and it appears that hydrophobic packing,
      rather than the cation-pi effect, is more likely to be responsible for the
      stability of this peptide. We conclude that any stabilizing effect of cation-pi
      interactions in these peptides is much smaller than that predicted from
      computational studies.

PMID- 15238640
TI  - Flexibility in the P2 domain of the HIV-1 Gag polyprotein.
AB  - The HIV-1 Gag polyprotein contains a segment called p2, located between the
      capsid (CA) and nucleocapsid (NC) domains, that is essential for ordered virus
      assembly and infectivity. We subcloned, overexpressed, and purified a 156-residue
      polypeptide that contains the C-terminal capsid subdomain (CA(CTD)) through the
      NC domain of Gag (CA(CTD)-p2-NC, Gag residues 276-431) for NMR relaxation and
      sedimentation equilibrium (SE) studies. The CA(CTD) and NC domains are folded as
      expected, but residues of the p2 segment, and the adjoining thirteen C-terminal
      residues of CA(CTD) and thirteen N-terminal residues of NC, are flexible.
      Backbone NMR chemical shifts of these 40 residues deviate slightly from random
      coil values and indicate a small propensity toward an alpha-helical conformation.
      The presence of a transient coil-to-helix equilibrium may explain the unusual and
      necessarily slow proteolysis rate of the CA-p2 junction. CA(CTD)-p2-NC forms
      dimers and self-associates with an equilibrium constant (Kd = 1.78 +/- 0.5
      microM) similar to that observed for the intact capsid protein (Kd = 2.94 +/- 0.8
      microM), suggesting that Gag self-association is not significantly influence by
      the P2 domain.

PMID- 15238641
TI  - Pamidronate in the treatment of childhood SAPHO syndrome.
AB  - BACKGROUND: SAPHO syndrome is increasingly recognized within the paediatric
      population. Conventional therapeutic approaches have often not been effective.
      Pamidronate is a second-generation bisphosphonate that affects bone turnover and
      demonstrates anti-inflammatory properties. In small case series it has given
      symptomatic relief to adults with this condition. OBJECTIVES: To report the
      clinical experience with pamidronate in childhood SAPHO syndrome. METHODS: A
      retrospective observational study of all children with SAPHO syndrome treated
      with pamidronate between 1996 and 2003 at a tertiary rheumatology centre. The
      standard dosing regime for pamidronate was 1 mg/kg to a maximum of 30 mg,
      administered daily for three consecutive days, repeated 3-monthly as required.
      Response to treatment was determined by clinical observation, patient subjective
      response and reduction in other treatments RESULTS: Seven girls were treated,
      with a median (range) age at diagnosis of 11 yr (9-15 yr). All patients
      demonstrated a beneficial clinical response, with relief of pain, increased
      activity and improved well-being. Subsequent courses of pamidronate were used in
      all patients. Other medications including corticosteroids and methotrexate could
      subsequently be stopped. Transient symptoms were associated with the initial
      course of pamidronate in some patients. No serious adverse events were reported.
      CONCLUSIONS: Pamidronate was associated with a marked improvement in function and
      well-being, and a reduction of pain and use of other medications in all patients,
      with no significant adverse effects. This study represents preliminary clinical
      data. A prospective multicentre study is necessary to assess the role and long
      term safety of pamidronate in the management of childhood SAPHO syndrome

PMID- 15238642
TI  - Effects of methotrexate on human bone cell responses to mechanical stimulation.
AB  - OBJECTIVES: Methotrexate (MTX), which is prescribed in the treatment of
      malignancy and autoimmune disease, has detrimental effects on a number of organ
      systems, including bone. At present, the exact mechanism of action of MTX on bone
      at the cellular level is unclear. Mechanical stimuli imparted by stretch,
      pressure, fluid flow and shear stress result in a variety of biochemical
      responses that are important in bone metabolism. Cyclical mechanical stimulation
      at 0.33 Hz induces rapid cell membrane hyperpolarization of human bone cells
      (HBC) via an integrin-mediated pathway which includes an IL-1beta
      autocrine/paracrine loop. This study was undertaken to investigate the effect of
      MTX on responses of HBC to 0.33 Hz mechanical stimulation. METHODS:
      Electrophysiological responses of HBC were measured before and after mechanical
      stimulation at 0.33 Hz in the presence or absence of MTX. Semiquantitative RT-PCR
      was used to investigate effects of MTX on relative levels of type-1 collagen and
      bone morphogenetic protein-4 (BMP-4) following 0.33 Hz mechanical stimulation.
      RESULTS: MTX dose-dependently inhibited HBC hyperpolarization in response to 0.33
      Hz mechanical stimulation. Production/release of IL-1beta was inhibited by MTX,
      whereas its effects on target cells were not. Mechanical stimulation of HBC at
      0.33 Hz caused a significant decrease in relative levels of BMP-4 mRNA, whereas
      relative levels of type-1 collagen mRNA were consistently increased, although
      these increases did not reach statistical significance. These trends were
      unaffected by MTX. CONCLUSIONS: These studies show that MTX affects HBC
      mechanotransduction by interfering with integrin-mediated signalling. The data
      also suggest that the mechanotransduction pathway responsible for the regulation
      of type-1 collagen and BMP-4 gene expression may be distinct from the IL-1beta
      mediated signalling pathway.

PMID- 15238643
TI  - Remission in rheumatoid arthritis: agreement of the disease activity score
      (DAS28) with the ARA preliminary remission criteria.
AB  - OBJECTIVE: To determine which cut-off point in the RA disease activity score
      (DAS28) corresponds to fulfilment of the ARA criteria for clinical remission.
      METHODS: The disease activity of patients included in the Nijmegen RA inception
      cohort was systematically assessed every 3 months. For all visits, a modification
      of the ARA preliminary criteria for clinical remission was applied and the DAS28
      was calculated. Receiver operating characteristic analysis was used to determine
      the cut-off point with maximum sensitivity and specificity in DAS28 corresponding
      with fulfilment of the modified ARA criteria. RESULTS: Three hundred and seventy
      eight patients contributed 4378 visits. In 6.5% of the visits four of the five
      items and in 1.5% all five items of the modified ARA criteria were fulfilled. The
      optimal cut-off point for the DAS28 that corresponds to fulfilment of the
      modified ARA criteria was determined to be 2.66. CONCLUSION: DAS28 <2.6
      corresponds to fulfilment of the preliminary ARA criteria for clinical remission
      in RA.

PMID- 15238644
TI  - Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm
      labelled nanocolloid scintigraphy. Study of early rheumatoid arthritis patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the roles of contrast-enhanced
      dynamic and static magnetic resonance imaging (MRI) and quantitative 99Tcm
      labelled nanocolloid (NC) scintigraphy in detecting wrist joint inflammation in
      early rheumatoid arthritis (RA) patients. METHODS: Twenty-eight early RA patients
      (median symptom duration 5 months, range 1-12 months) underwent MRI, NC
      scintigraphy, laboratory and clinical examinations. Static wrist MRI scans were
      retrospectively scored for synovitis, bone oedema and erosions by two independent
      readers using the recently published rheumatoid arthritis MRI scoring system
      (RAMRIS). Twenty NC scans were analysed quantitatively by measuring maximum 99Tcm
      NC uptake in three small areas of each wrist. From the same locations on the
      wrists, dynamic MRI gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA)
      enhancement rates (E-rate) were measured. The average 99Tcm-NC uptake of the
      whole wrist region was also measured and average E-rates were calculated.
      Correlations between MRI and NC scintigraphy measurements were calculated.
      Correlations between imaging methods of the wrist and the global measures of
      inflammation (laboratory and clinical examinations) were also assessed. RESULTS:
      Strong correlations emerged between maximal 99Tcm-NC uptake and MRI E-rates,
      reflecting similar performance of the methods in detecting local synovial
      inflammation. 99Tcm-NC uptake and MRI E-rate correlated with semiquantitative
      scoring of synovitis and bone oedema from static MRI scans. The erythrocyte
      sedimentation rate (ESR) correlated with MRI scores, E-rate and 99Tcm-NC uptake.
      No correlation between the clinical parameters and the imaging methods was
      detected. Inter-observer reliability for scoring synovial hypertrophy, bone
      oedema and bone erosions from static MR images were high (single-measure fixed
      effects intra-class correlations 0.87, 0.93 and 0.91 respectively). Intra
      observer reliability for E-rate and 99Tcm-NC measurements of 10 randomly picked
      scans was found to be high, with an intra-class correlation of 0.92; 95%
      confidence interval (CI) 0.84-0.96 and 0.99; 95% CI 0.98-1.00, respectively.
      CONCLUSIONS: Objective information about wrist joint inflammation can be obtained
      with contrast-enhanced dynamic MRI and quantitative 99Tcm-labelled NC
      scintigraphy. MRI also allows visualization and semiquantitative scoring of bone
      oedema and erosions of the wrist. Dynamic MRI and NC scintigraphy are safe and
      easy to perform, and they can be used in a long-term follow-up of rheumatoid
      patients.

PMID- 15238645
TI  - Differences in the relationship of specificity to titre and functional affinity
      between circulating Ga- and pan-reactive IgM rheumatoid factors in rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine if there are the differences in titre and functional
      affinity for immunoglobulin (Ig) G subclasses and glycoforms between the Ga- and
      pan-specific IgM rheumatoid factors (RFs) present in the sera of patients with
      rheumatoid arthritis (RA), and to determine whether these two broad specificities
      have different functional roles in RA. METHODS: We used direct ELISA and modified
      ELISA to study the binding of IgM RF in the sera of 32 patients with RA with a
      range of RF titres to a panel of 14 IgG paraproteins of all four subclasses, some
      allotypes and different glycosylation patterns. RESULTS: Pan-specific RFs were
      mostly found in RA sera with high RF titres, and these RFs generally had higher
      avidity. A trend towards higher avidity of RFs with higher titre was observed for
      pan-specific, but not for Ga-specific RFs. With increasing titre, pan-specific
      RFs tended to react strongly with fucosylated and bisected variants of
      hypogalactosylated IgG3 of G3m(b1) allotype and hypergalactosylated IgG4 of 4a
      allotype. CONCLUSION: Among high-titred pan-specific IgM RFs, there is a
      subpopulation responsible for strong anti-IgG activity in RA. The possible
      mechanisms of production of pan- and Ga-specific RFs are discussed.

PMID- 15238646
TI  - Influence of previous open synovectomy on the outcome of Souter-Strathclyde total
      elbow prosthesis.
AB  - OBJECTIVES: Open synovectomy of the elbow joint is often performed in early
      stages of rheumatoid arthritis. Because of poor long-term results after
      synovectomy, insertion of a total elbow prosthesis is commonly used as a
      secondary procedure. The aim of this study is to evaluate the influence of
      previous synovectomy on the outcome after placement of a total elbow prosthesis.
      METHODS: We inserted 204 primary Souter-Strathclyde total elbow prostheses for
      rheumatoid arthritis. Two groups could be distinguished: group A with previous
      synovectomy 3.9 yr (mean) before the elbow replacement (n = 33) and group B
      without previous synovectomy (n = 171). The mean follow-up was 5.8 yr for group A
      and 6.3 yr for group B. All patients were assessed clinically and radiologically
      before the operation, 1 and 2 years later and then at regular intervals. The
      effect of previous synovectomy was analysed via a Cox model and a generalized
      linear mixed model for binomial data with multivariate normal random effects.
      RESULTS: No statistically significant effect of previous synovectomy on pain,
      function or complaints of the ulnar nerve could be found post-operatively. The
      post-operative flexion was significantly higher in group B than in group A. The
      complication-rates were similar for both groups. The overall survival rate for
      respectively group A and B with revision as endpoint was 66.9% (s.e. 13.4) versus
      79.6 (s.e. 4.3) after 10 yr. CONCLUSIONS: Previous synovectomy does not diminish
      the outcome after total elbow prosthesis in this series and could therefore be
      considered in early, painful stages of rheumatoid destruction of the elbow joint.

PMID- 15238647
TI  - Introduction: off-site nuclear emergency management--capabilities and challenges.

PMID- 15238648
TI  - The long-term management of nuclear emergencies: the principles.
AB  - The long-term impact of the Chernobyl accident on the most affected populations
      in Belarus, Ukraine and the Russian Federation is still evident in terms of a
      continuing elevated level of thyroid cancer, prominent psychosocial effects, a
      depressed economy and a low level of well being. Some of these impacts are
      directly and primarily attributable to exposure to ionising radiation, while
      others have more complex origins and have evolved over the period since the
      accident. It is argued that although these latter impacts were largely
      unpredictable at the time of the accident, they could have been minimised had an
      appropriate management plan been in force. The principles underlying such a
      management plan for use in future accidents are enumerated. An essential
      component in further developing such a plan would be a thorough review of the
      experience of the Chernobyl accident in order to 'learn the lessons' that
      accident holds.

PMID- 15238649
TI  - Emergency management in the early phase.
AB  - An overview of response management in the early phase of an emergency at a
      nuclear installation is provided from a systems approach. This starts with the
      recognition of response goals, and using detailed analyses of threats, past
      experience, international law and principles, a response strategy is developed.
      The process is illustrated for the case of severe accidents at pressurized water
      reactors (PWRs) and identifies the need for and nature of: emergency
      classification based on plant conditions, notification, radiological monitoring
      and assessment strategies, operational criteria for implementing protective
      action decisions and management of public information. From the strategy
      detailed, functional and infrastructure requirements can be defined. The paper
      also presents some reflections on the key differences between response to
      emergencies arising from accidents and those arising from deliberate acts; on the
      preparedness and response capabilities of States, highlighting areas where
      generic improvements are needed and how best to achieve that.

PMID- 15238651
TI  - Assessment and evaluation of the radiological situation in the late phase of a
      nuclear accident.
AB  - An overview of existing approaches on assessing and evaluating the radiological
      situation in the late phase of a nuclear accident is given in this paper. Special
      attention is paid to the weak points of existing approaches and to problems to be
      solved in the future. Assessment of the radiological situation can be based on
      both monitoring data and model predictions. Approaches have been developed for
      many years in both categories and have meanwhile reached some kind of maturity
      and also operational applicability. Nevertheless, some areas exist where
      significant improvements could be achieved in the near future, e.g. by combining
      monitoring data and model predictions, by improving the modelling of urban areas
      or by improving existing radioecological models.

PMID- 15238650
TI  - Can the confidence in long range atmospheric transport models be increased? The
      pan-european experience of ensemble.
AB  - Is atmospheric dispersion forecasting an important asset of the early-phase
      nuclear emergency response management? Is there a 'perfect atmospheric dispersion
      model'? Is there a way to make the results of dispersion models more reliable and
      trustworthy? While seeking to answer these questions the multi-model ensemble
      dispersion forecast system ENSEMBLE will be presented.

PMID- 15238652
TI  - Using plant status data for off-site emergency management: technical and
      political aspects.
AB  - Subsequent to the TMI and Chernobyl accidents, emergency management is
      investigating the possibility of taking balanced decisions on interventions as
      early as possible. This process relies more and more on in-plant data to assess
      the term of releases. The paper discusses the regulatory aspects of the
      communication related to the source term between the utility and the national
      authorities, and the authorities of a host country and neighbouring countries
      that may be affected. The technical aspects of the assessment process are
      summarised, with the emphasis on the handling of uncertainties. Notwithstanding
      the technical progress, the main dilemma for the decision makers remains the
      same. Risk management and prevention measures become more familiar to
      authorities. Utilities and national authorities have to get rid of complexes with
      respect to accidents covered by the accepted residual risk. International
      emergency management has to look for an organisation type ensuring the continuity
      of countermeasures independent of the presence of administrative borders, and
      with respect to national autonomies.

PMID- 15238653
TI  - SPRINT: a tool for probabilistic source term prediction for use with decision
      support systems.
AB  - This paper describes a software tool, SPRINT, that has been developed within the
      FP5 STERPS project for rapid source term prediction. It is based entirely on a
      probabilistic approach to the diagnosis and prognosis of Nuclear Power Plant
      status, based on key instrument readings and other observations. In principle,
      the method can be applied to any accident sequence from the benign to the most
      severe. However, the main benefits are seen for the diagnosis of plant status
      during degraded core conditions where the accident phenomenology is either
      uncertain or essentially non-deterministic in nature. The output from SPRINT
      consists of a set of potential source terms with an estimate of the likelihood of
      each.

PMID- 15238654
TI  - Information and interaction with the public.
AB  - The general requirements of public information are stipulated in EU and IAEA
      documents. During the emergency exercises Slovenian authorities gained experience
      how to provide timely and accurate information to the population in the emergency
      planning zone and to other population in Slovenia. In the future a dialogue
      should be established between the authorities and the public during an emergency,
      and not only one-way information flow. The response of the public in relation to
      the information provided should be constantly monitored and the need for
      additional information should be addressed without undue delay.

PMID- 15238655
TI  - Protective actions in the late phase--intervention criteria and decision-making.
AB  - Major countermeasures in the late phase of a nuclear or radiological accident
      where long-lived radionuclides have been dispersed in the environment are
      relocation/resettlement, foodstuff restrictions, agricultural countermeasures and
      clean-up of contaminated areas. There has essentially been a broad acceptance
      internationally of the principles for their introduction, but it has not been
      possible to reach an agreement for the purpose of defining a net benefit based
      upon the exact weighting to be attached to each of the attributes influencing the
      decision on intervention, e.g. socio-psychological attributes. Optimisation of
      protection, i.e. maximising the net benefit, is not a question of developing
      radiation protection philosophy to fully include socio-psychological factors but
      rather to include these factors--in parallel with the radiological protection
      factors--in cooperation between radiation protection experts and e.g. experts in
      social and psychological sciences under the responsibility of the decision-maker,
      who will take the final decision on the introduction of long-term
      countermeasures.

PMID- 15238656
TI  - Methodology and tools for source term assessment in case of emergency.
AB  - By looking at the power plant state of fission product barriers and critical
      safety systems, the magnitude of a potential radioactive release could be
      predicted in a timely manner to allow emergency response to be executed even
      before the occurrence of a release. This is the perspective in which the
      development of ASTRID methodology and tool is performed. The methodology maps
      out, for several reactor types as well as reactor containments, relevant process
      parameters and indicators, what and how to calculate and a structured way to
      summarise and conclude on potential source term and likely time projections. A
      computer tool is proposed to support the methodology, to suite different user
      situations, both on-site and off-site as well as size of staff, priority and work
      order. The output from such an assessment is intended to, first, give bases for
      decisions on necessary urgent protective actions pre-release, and, second, an
      input for the sophisticated dispersion calculation codes.

PMID- 15238657
TI  - International data- and information exchange for off-site emergency management-
      where to go?
AB  - The communication and exchange of views and opinions between decision makers and
      their advisers is crucial for coherent crisis management. As a vision, the
      concept of a 'Virtual Round Table' is proposed. It stands for the dedication of
      all accountable authorities to cross border cooperation and should provide a
      comprehensive technical infrastructure enabling decision makers and experts to
      communicate with their colleagues in neighbouring countries as if they were
      sitting at the same table. Organisational arrangements must be in place for
      coordinating decisions. The technical infrastructure should comprise modern
      communication technologies such as video conferencing and a 'Common Information
      Board', which presents all relevant information and documents in a structured
      way, manages alerting, decision journaling, data distribution and access control.
      In order to achieve this goal in an evolutionary approach, existing procedures of
      good practice are analysed and helpful features are identified.

PMID- 15238658
TI  - A critical evaluation of the strategy project.
AB  - The STRATEGY project (sustainable restoration and long-term management of
      contaminated rural, urban and industrial ecosystems; www.strategy-ec.org.uk)
      addressed the need for a holistic decision framework for the selection of optimal
      remediation strategies for long-term sustainable management of contaminated areas
      in Western Europe. The project considered both technical and social aspects of
      implementing restoration strategies for urban and rural environments. The
      importance of considering socially relevant objectives in addition to the dose
      reduction was emphasised. A critical evaluation was carried out on 101 selected
      countermeasures, (including rural waste disposal options), a model was developed
      to aid optimising countermeasure strategies and a method of carrying out
      participatory decision-making suggested. The outputs of the project are described
      and critically evaluated.

PMID- 15238659
TI  - Regional long-term co-operation in the field of nuclear and radiation emergency
      preparedness.
AB  - Emergency preparedness is generally covered by methodical and coordinative
      activities of the International Atomic Energy Agency (IAEA) in Member States of
      the IAEA and by the European Commission (EC) in EU Member and EU Accession
      Countries. However, the regional harmonisation of emergency arrangements is an
      important trend of emergency preparedness. The present paper gives a couple of
      illustrative examples for a regional co-operation in the field of emergency
      preparedness in Central Europe and an overview on international exercises in this
      region. The penultimate section contains an outlook on future activities
      regarding regional co-operation in Central Europe. The following topics have been
      suggested inter alia: the harmonisation of intervention criteria and
      countermeasures, co-ordination in the field of information of the public,
      comprehensive bi lateral and multilateral exercises, exchange of experts between
      the national nuclear emergency centres and inter-comparison calculations of the
      computer codes.

PMID- 15238660
TI  - A United States perspective on long-term management of areas contaminated with
      radioactive materials.
AB  - The US has far-reaching and extensive experience in the long-term management of
      areas contaminated with radioactive materials. This experience base includes the
      Department of Energy's continued follow-up with Hiroshima and Nagasaki from the
      1940s at the Radiological Effects Research Foundation in Hiroshima, Japan, the
      long-term management of the Marshall Islands Programme, the clean-up of the US
      nuclear weapons complex and the ongoing management of accident sites such as in
      Palomares, Spain. This paper discusses the lessons learnt and best practices
      gained from this far-reaching and extensive experience in the long-term
      management of areas contaminated with radioactive materials.

PMID- 15238661
TI  - Radiation monitoring strategy: factors to be considered.
AB  - In a nuclear or radiological emergency radiation measurements provide
      indispensable data needed in the management of the situation at hand. In order to
      assess the possible consequences correctly and to carry out proper
      countermeasures on time, the authorities must have a pre-prepared monitoring
      strategy at their disposal. There are, however, many different factors that
      affect a strategy. Thus, drawing up a comprehensive yet realistic emergency
      monitoring strategy is far from being an easy task. Some of the key factors
      related to strategies are reviewed and a simple way of producing a strategy plan
      is presented.

PMID- 15238662
TI  - Off-site nuclear emergency management.
AB  - Urgent protective measures for the possibly affected population in the pre
      release and release phase of a nuclear accident are decided upon and implemented
      by civil protection authorities on regional and local level. The responsible
      officers of these authorities are experienced in emergency response, but not in
      radiological questions. Their radiological advisors, on the other hand, mostly
      coming from surveillance agencies, often lack knowledge about conditions framing
      practical response measures. Moreover, although the scientific basis of
      protective measures is unquestionable, implementation policies are widely
      different in different countries and render co-ordination of response in border
      areas difficult. Finally, decreasing availability of funds sharpens the already
      existing problems due to diminishing interest of young scientists in radiation
      protection. Measures to improve upon the situation and prerequisite conditions
      will be discussed.

PMID- 15238663
TI  - Response in the late phase to a radiological emergency.
AB  - This paper looks at the key issues that need to be addressed during the
      transition from the emergency phase to the late phase of a radioactive release,
      and the development of the initial late phase strategy. It discusses the extent
      to which current national plans and international advice address the needs of
      decision makers following contamination of inhabited areas and food production
      systems. Based on this the following recommendations are made: (1) the issues
      that will arise at the start of the late phase response to a radioactive release
      require preparation work in advance of any release; (2) this preparation should
      consider the adequacy of legislation, technical data and modelling, options for
      waste storage and disposal, resources for monitoring and implementing clean up;
      (3) late phase preparedness requires regular exercising and (4) the possibility
      of terrorist releases adds further emphasis to the need for preparedness for the
      late phase.

PMID- 15238664
TI  - Emergency management: does it have a sufficiently comprehensive understanding of
      decision-making, process and context?
AB  - It is widely recognised in the social and management sciences that the effective
      support of decision-making requires a multidisciplinary perspective. This trend
      is also clear in nuclear emergency management (EM). However, communication
      between disciplines is not easy to maintain in EM contexts when the decision
      makers (DMs) are likely to be highly stressed. Such circumstances can lead them
      to revert to the instinctive patterns of perception of their core disciplines,
      making communication between disciplines difficult and, perhaps, obscuring
      complex interactions that have not been rehearsed in practice exercises. This
      paper explores decision making in EM and the nature of the socio-technical issues
      that will arise, suggesting that despite the lessons of past accidents the
      research EM community is still not taking a broad enough view of what future
      incidents may entail.

PMID- 15238665
TI  - Overview of the wisdom stakeholder workshop on restoration management.
AB  - A Workshop to extend the Involvement of Stakeholders in Decisions On restoration
      Management (WISDOM) was held at New College, Oxford from 15 to 17 September 2003.
      The aim was to promote awareness and interest in the wider application of
      stakeholder involvement in the formulation of strategies for the management of
      contaminated agricultural land and produce following a nuclear accident. The
      workshop, through 25 plenary papers and a set of two facilitated discussion
      sessions, provided valuable feedback on a wide range of issues including
      technical and social factors affecting countermeasure selection, acceptability of
      intervention levels, the challenges of rural waste disposal and crisis
      management. The workshop achieved its aim and the findings will be disseminated
      widely. Stakeholder groups are already active in the UK, Finland, Belgium, France
      and Greece; there was commitment from participants to establish further, similar
      groups in other member states within the European Union.

PMID- 15238666
TI  - The Austria-Czech Republic co-operation in the field of radiation-emergency
      preparedness.
AB  - An overview on the long-term information exchange and co-operation between
      Austria and the Czech Republic in the field of radiation emergency preparedness
      and evaluation of radiological consequences of NPP accidents is provided.
      Initiated by the 'Melk Protocol' between the Czech and Austrian governments in
      December 2000 and its follow-up activities, the information exchange and co
      operation between the Czech Republic and Austria in the field of radiation
      emergency preparedness have been extended. Among others, a Working Group to
      compare radiological consequences of Beyond Design Basis Accident with a detailed
      inter-comparison program concerning atmospheric dispersion models, dose
      assessment methods and counter- measures was established. Based on this
      experience, an area for future co-operation in the field of emergency
      preparedness and information exchange between the Czech Republic and Austria is
      discussed.

PMID- 15238667
TI  - Is there a need for hydrological modelling in decision support systems for
      nuclear emergencies.
AB  - This paper discusses the role of hydrological modelling in decision support
      systems for nuclear emergencies. In particular, most recent developments such as,
      the radionuclide transport models integrated in to the decision support system
      RODOS will be explored. Recent progress in the implementation of physically-based
      distributed hydrological models for operational forecasting in national and
      supranational centres, may support a closer cooperation between national
      hydrological services and therefore, strengthen the use of hydrological and
      radiological models implemented in decision support systems.

PMID- 15238668
TI  - Better use of European (regional) resources.
AB  - In case of an accidental release of radioactivity and subsequent contamination of
      the food chain, many samples need to be collected and analysed, and this is far
      from being a simple issue. The determination of contamination levels requires
      accredited laboratories, approved and certified procedures and methods,
      transparency and above all prompt results, as stakeholders in general cannot
      afford waiting. Adequate decisions require fixed norms, stable in time, and
      accepted internationally. Moreover, an effective policy relies on traceability of
      products as well. There are huge requirements of harmonisation of procedures,
      traceability of data, database management, priority settings etc. Accredited
      laboratories tend to make use of reliable techniques but these have been
      optimised for low radiation levels and high accuracy for routine analyses, often
      in the framework of radiological surveillance of the territory, drinking waters
      or the food chain. It is obvious that such procedures, although very accurate and
      sensitive, are not suited for urgent decisions in crisis situations. Similarly,
      accredited analysis methodologies may start from large quantities of product in
      order to decrease limits of detection; however, this involves sometimes long
      times for drying or chemical treatment, introducing important delays.
      Furthermore, large quantities of samples would simply result in the saturation of
      the analytical capabilities of one country. Adequate actions and informed
      decisions during a nuclear accident will require an analytical infrastructure
      that individual countries do not have; hence there is a clear need to establish
      regional collaboration and co-operation. This paper includes an example of such
      collaborative work and mutual assistance, and also touches on how sharing tools
      for decision making, analytical resources, sample collection procedures and
      analysis would promote trust, reliablity in the results, a common approach toward
      minimizing the effects of a radiological disaster and above all unity. Last but
      not least, this paper also poses a challenge: Nuclear accident management implies
      that all responsible parties have to guarantee that decision support systems have
      access to data and information in the best available and consistent manner. This
      will not be achieved in an independent and isolated manner.

PMID- 15238669
TI  - Demonstrating the European capability for airborne gamma spectrometry: results
      from the eccomags exercise.
AB  - Airborne gamma spectrometry (AGS) is being increasingly recognised as an
      important means for mapping environmental radioactivity in emergency response.
      Progress has been made in recent years towards methodological convergence and
      cooperation between European teams. Recently, an international comparison was
      undertaken in SW Scotland in 2002 to evaluate AGS and ground-based methods. Teams
      from 18 institutions in 10 European countries attended, collecting some 140,000
      AGS spectra, with 750 laboratory gamma spectrometry analyses and 120 in situ
      observations from the ground sites. Comparisons between AGS and ground-based
      methods have confirmed the validity of AGS protocols. A composite mapping task,
      where AGS teams recorded data over adjacent parts of a 90 x 40 km2 area within a
      few days, confirmed the ability of teams to work together in an effective manner.
      This paper provides a summary of the results of the exercise. These demonstrate
      the operational capabilities of European AGS teams and confirm the quantitative
      nature of the method.

PMID- 15238670
TI  - Experiences in methods to involve key players in planning protective actions in
      the case of a nuclear accident.
AB  - A widely used method in the planning of protective actions is to establish a
      stakeholder network to generate a comprehensive set of generic protective
      actions. The aim is to increase competence and build links for communication and
      coordination. The approach of this work was to systematically evaluate protective
      action strategies in the case of a nuclear accident. This was done in a way that
      the concerns and issues of all key players could be transparently and equally
      included in the decision taken. An approach called Facilitated Decision Analysis
      Workshop has been developed and tested. The work builds on case studies in which
      it was assumed that a hypothetical accident had led to a release of considerable
      amounts of radionuclides and, therefore, various types of countermeasures had to
      be considered. Six workshops were organised in the Nordic countries where the key
      players were represented, i.e. authorities, expert organisations, industry and
      agricultural producers.

PMID- 15238671
TI  - International exchange of emergency phase information and assessments: an aid to
      national/international decision makers.
AB  - This paper discusses a collaborative project (1) to demonstrate the feasibility
      and benefit of a system seeking early review, in a 'quasi peer review' mode, of
      nuclear accident plume and dose assessment predictions by four major
      international nuclear accident emergency response systems before release of
      calculations to respective national authorities followed by (2) sharing these
      results with responsible national/international authorities, (3) development of
      an affordable/accessible system to distribute results to countries without
      prediction capabilities and (4) utilisation for exercises and collaboration
      studies. The project exploits Internet browser technology and low-cost PC
      hardware, incorporates an Internet node, with access control, for depositing a
      minimal set of XML-based graphics files for presentation in an identical map
      format. Side-by-side viewing and televideo conferencing will permit rapid
      evaluation, data elaboration and recalculation (if necessary) and should produce
      strong consensus among decision makers. Successful completion affords easy
      utilisation by national/international organisations and non-nuclear states at
      risk of trans-boundary incursion.

PMID- 15238672
TI  - Airborne gamma spectrometry--towards integration of European operational
      capability.
AB  - Airborne gamma spectrometry is an excellent tool for finding out in a timely
      manner the extent and magnitude of the dispersion of radioactive materials
      resulting from a nuclear disaster. To utilise existing European airborne
      monitoring capabilities for multilateral assistance in an accident is a complex
      administrative and technical matter. Several international exercises have been
      organised demonstrating the capability to cooperate. However, efficient mutual
      assistance between European countries requires conceptual work, standards and
      harmonisation of software. A unified radiological vocabulary and data exchange
      format in XML need to be developed. A comprehensive database is essential for
      data assimilation. An operations centre is needed for management and planning of
      surveys.

PMID- 15238673
TI  - Belarus: towards a new post-chernobyl rehabilitation strategy.
AB  - Today, Belarus still has to deal with many problems that resulted owing to the
      extensive contamination of its territory after the Chernobyl accident. These
      problems remain omnipresent in everyday life of the affected population and have
      a continuous impact on the economic well being of the country. This paper
      describes the major changes that have been carried out in the rehabilitation
      strategies in Belarus since the Chernobyl accident. The evolution of the legal
      and administrative framework for rehabilitation and actions taken in this context
      over the past two decades are summarized. The continuing challenges faced by the
      population in the affected areas are discussed and the key principles underlying
      rehabilitation strategies (that are both practicable and accepted) are
      identified. The latter include openness, voluntary participation, collective
      decision-making and empowerment of local population and professionals. These
      principles have underpinned the development of recent national and international
      initiatives that are described.

PMID- 15238674
TI  - Enhancing nuclear emergency response through international cooperation.
AB  - Nuclear and radiological emergencies may easily become severe international
      emergencies requiring substantial resources in several or many states for an
      adequate response, which in some cases may require resources exceeding national
      capabilities. Through the development of a consistent, coherent and sustainable
      joint programme for improved and more efficient international responses to
      nuclear and radiological emergencies, it is believed that we could achieve a
      better and more cost-effective response capability for nuclear and radiological
      emergencies. This requires, however, that we be willing and able to establish
      mechanisms of assistance where information and resources are globally shared and
      that standardised/harmonised procedures be developed and implemented. If we are
      willing to make this investment, we believe that, in the long term, there will be
      a significant benefit for all of us.

PMID- 15238675
TI  - Ongoing efforts to improve the international nuclear and radiological emergency
      response.
AB  - It is recognised that states, through the development of a consistent, coherent
      and sustainable joint programme for improved and more efficient international
      responses to nuclear and radiological emergencies, could achieve a better and
      more cost-effective response capability. Enhanced efforts by IAEA member states
      and the IAEA secretariat to improve the implementation of the Convention on Early
      Notification of a Nuclear Accident and the Convention on Assistance in Case of a
      Nuclear Accident or Radiological Emergency have been initiated, establishing a
      national competent authority coordination group (NCACG) and a long-term action
      plan for the work.

PMID- 15238676
TI  - Maintaining competence in radiological protection in emergency situations: a
      challenge for the 21st century.
AB  - State-of-the-art radiological protection in emergency situations requires
      specific technical resources, qualified personnel and competence in a variety of
      scientific and technical areas. In many developed countries a high technical
      standard is available currently in these areas. There are, however, strong
      indicators that future expertise is at risk. The indicators are declining
      university enrolment, dilution of university course content and high retirement
      expectations of staff members, with little or no replacement planned. This paper
      describes the underlying problem and makes recommendations for an action plan
      that includes both short-term actions and a long-term strategy to minimise the
      emerging risks. A strategic approach will be required to stop the decline and to
      avoid a drop in competence to an unacceptable level.

PMID- 15238677
TI  - Summary and conclusions: capabilities and challenges.

PMID- 15238678
TI  - Off-site nuclear emergency management-capabilities and challenges. Proceedings of
      an international symposium. September 29- October 3, 2003. Salzburg, Austria.

PMID- 15238680
TI  - B6 mice and Plasmodium yoelii.

PMID- 15238682
TI  - America in the world: 100 years of tropical medicine and hygiene.

PMID- 15238684
TI  - Relationship of anti-microbial activity of tetracyclines to their ability to
      block the L3 to L4 molt of the human filarial parasite Brugia malayi.
AB  - The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a
      human disease known as lymphatic filariasis, which afflicts approximately 120
      million people worldwide. These organisms are known to contain endosymbiotic
      bacteria (Wolbachia) that are related to rickettsiae. It has been previously
      reported that tetracycline blocks the L3 to L4 molt of the filarial parasite B.
      malayi, and suggested that this was related to their known anti-rickettsial
      activity. However, this interpretation was tempered by several observations.
      First, Wolbachia DNA could still be detected in nematodes from tetracycline
      treated cultures. In addition, chloramphenicol, which has anti-rickettsial and
      anti-chlamydial activity, failed to inhibit the molt. These observations could
      not rule out the possibility that the anti-molting activity of tetracycline is
      due to pharmacologic activities unrelated to its anti-rickettsial functions. This
      study shows that chemically modified tetracycline, which does not to have anti
      microbial activity, also blocks molting.

PMID- 15238683
TI  - Contrasting Wuchereria bancrofti microfilaria rates in two Mangyan-populated
      Philippine villages.
AB  - Lymphatic filariasis caused by infection with Wuchereria bancrofti and Brugia
      malayi is endemic in 45 of 77 provinces in The Philippines. To prepare the island
      of Mindoro for mass treatment using diethylcarbamazine and albendazole, complete
      census data were collected in rural villages. A sample of individuals selected
      from each of two adjacent villages was examined for microfilaremia. Microfilariae
      were detected from thin smears in 34 (13%) of 272 patients examined from the
      village of Bayanan and 10 (3.4%) of 292 in the village of Mangangan (P < 0.01, by
      chi-square test). In these villages, the majority of those infected were members
      of the ethnic group known as Mangyans: 33 (97%) of 24 in Bayanan and 7 (70%) of
      10 in Mangangan (risk ratio = 89, 95% confidence interval = 33-240, P < 0.001.)
      In children examined who were less than 10 years of age (n = 165), girls were
      more commonly infected than boys, even though the proportion of males in the
      general population was greater. Understanding sociocultural characteristics and
      related behaviors in future observations among the Mangyan may help to explain
      local differences in the distribution of filariasis. This information should also
      be helpful in designing more culturally appropriate strategies for the control of
      lymphatic filariasis among ethnic minorities in The Philippines.

PMID- 15238685
TI  - Analysis of circumsporozoite protein-specific immune responses following recent
      infection with Plasmodium vivax.
AB  - CD8(+) and CD4(+) T cells are involved in immunity to the pre-erythrocytic stage
      of malaria. This study has been undertaken to define T cell epitopes on the
      Plasmodium vivax circumsporozoite protein (CSP) and to analyze the early
      induction of immune response following infection. We identified CD4(+) and CD8(+)
      T epitopes recognized by different strains of mice as well as by humans. The
      CD4(+) T cell response in mice was found to be similar in all strains, but
      variation between strains was evident. Five H-2(d)-restricted CD8(+) cytotoxic T
      lymphocyte (CTL) epitopes, but no H-2(k)-or H-2(b)-restricted epitopes, could be
      defined. Non-H-2 genes were also able to regulate the response. In recently
      infected Thai adults, poor immunoresponsiveness was demonstrated. CTL activity
      and proliferative responses of T cells from malaria-exposed donors were very low.
      In contrast, exposed individuals had specific antibodies against the
      immunodominant repeats of both common strains of the P. vivax CSP; however,
      titers decreased following treatment.

PMID- 15238686
TI  - Short report: polymorphisms in the chloroquine resistance transporter gene in
      Plasmodium falciparum isolates from Lombok, Indonesia.
AB  - The polymorphisms in the Plasmodium falciparum multidrug resistance 1 (pfmdr1)
      and P. falciparum chloroquine resistance transporter (pfcrt) genes, which are
      associated with chloroquine resistance, were examined in 48 P. falciparum
      isolates from uncomplicated malaria patients from the West Lombok District in
      Indonesia. The point mutation N86Y in pfmdr1 was present in 35.4% of the isolates
      and mutation K76T in pfcrt was found in all but one of the samples studied.
      Identified pfcrt haplotypes were mainly identical to the Papua New Guinea type
      S(agt)VMNT (42 of 48, 87.5%), and a few isolates had the Southeast Asia type
      CVIET (5 of 48, 10.4%). Moreover, one P. falciparum isolate harbored the K76N
      mutation, giving rise to the haplotype CVMNN, which was not previously reported
      in field isolates. Our findings suggest that chloroquine resistance in this area
      might have the same origin as in Papua New Guinea.

PMID- 15238687
TI  - Carboxyhemoglobin levels in Kenyan children with Plasmodium falciparum malaria.
AB  - Heme oxygenase (HO) is thought to be induced in severe malaria, but the
      pathophysiologic consequences have not been examined. It is induced by hemolysis,
      oxidative stress, and inflammation. It degrades heme, producing carbon monoxide
      (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective
      study of 1,520 children admitted to a Kenyan district hospital, COHb levels were
      no higher in children with malaria than with other infections. The COHb levels in
      children with severe malarial anemia were higher than in other children with
      malaria, but significantly lower than in children with other causes of severe
      anemia such as sickle cell disease. Levels of COHb were not significantly higher
      in children with cerebral malaria or in those dying of malaria. These results do
      not support a systemic increase in HO activity in malaria compared with other
      infectious diseases, but the roles of HO and CO in malaria require further study.

PMID- 15238688
TI  - Risk factors for human anthrax among contacts of anthrax-infected livestock in
      Kazakhstan.
AB  - A retrospective cohort analysis was conducted in Kazakhstan to define modifiable
      risk factors during seven outbreaks of human anthrax. Fifty-three cases and 255
      non-ill persons with an epidemiologic link to an infected animal were enrolled.
      Cases were 58% male and had a median age of 35 years (range = 5-71). Nearly all
      cases had cutaneous disease (96%). Two patients (4%) were diagnosed with
      gastrointestinal disease. Although all cases had some contact with an infected
      animal other than consumption, in multivariable analysis the act of butchering an
      animal (relative risk [RR] = 3.6, 95% confidence interval [CI] = 1.5-9.6) and the
      presence of visible cuts on the hands were associated with anthrax (RR = 3.0, 95%
      CI = 0.9-9.6). Contact with infected livestock, in particular butchering, is
      associated with developing anthrax. The risk may be exacerbated by the presence
      of cuts on the hands at the time of contact with the animal or animal products.

PMID- 15238689
TI  - Report of an unusual case of persistent bacteremia by Bartonella bacilliformis in
      a splenectomized patient.
AB  - We report a case of a 56-year-old man with a history of splenectomy for
      idiopathic thrombocytopenic purpura who developed persistent bacteremia in the
      acute phase of human bartonellosis. This patient did not develop hemolytic
      anemia. Only after several courses of antibiotic treatment was the infection
      eradicated. This is an unusual case of overwhelming post-splenectomy infection by
      Bartonella bacilliformis, which provides clinical evidence that the spleen is a
      critical effector organ of clearance of this infection as well as the effector
      organ of bartonellosis-associated hemolytic anemia.

PMID- 15238690
TI  - Use of disability adjusted life years in the estimation of the disease burden of
      echinococcosis for a high endemic region of the Tibetan plateau.
AB  - Shiqu County, located on the Tibetan plateau of western China, has an extremely
      high prevalence of both human alveolar echinococcosis (AE), and cystic
      echinococcosis (CE). The short form 12 version 2 quality of life survey, which
      was used to evaluate the extent to which morbidity associated with echinococcosis
      should be accounted, verified that there was a significant reduction in the mean
      health scores in all categories for individuals diagnosed with abdominal
      echinococcosis compared with an age and sex cross-matched population. Results of
      a larger ultrasound survey, which screened 3135 subjects, demonstrated that the
      prevalence rates of AE and CE were both approximately 6% with a combined
      prevalence rate of 11.4%. Prevalence rates adjusted for the age and sex structure
      of Shiqu County were 4.6% for AE and 4.9% for CE with an estimated overall
      adjusted prevalence rate of 9.5%. The burden of disease associated with
      echinococcosis was calculated using disability adjusted life years (DALYs) based
      on these estimated prevalence rates. Monte-Carlo techniques were used to model
      the uncertainty in the prevalence estimates and the disability weights. Using
      these methods, we estimated that the total numbers of DALYs lost due
      echinococcosis was 50,933 (95% confidence interval [CI] = 41,995-61,026). The
      DALYs lost consisted of approximately 32,978 (95% CI = 25,019-42,422) due to AE
      and 17,955 (95% CI = 14,268-22,128) due to CE and suggests an average of
      approximately 0.81 DALY lost per person. This study has clearly shown that the
      impact of DALYs lost due to echinococcosis, in terms of medical treatment costs,
      lost income, and physical and social suffering, is likely to be substantial in
      this highly endemic region of China.

PMID- 15238691
TI  - Risk of Giardia intestinalis infection in children from an artificially recharged
      groundwater area in Mexico City.
AB  - The objective of this study was to assess the risk of infection with Giardia
      intestinalis in children living in an area with artificial groundwater recharge
      and potable water reuse in Mexico City. Eligible wells and surrounding homesteads
      were defined by using a geographic information system. Five wells were tested for
      G. intestinalis cysts per 400 liters of water. A total of 750 eligible households
      were visited during two cross-sectional surveys. Stool samples were provided by
      986 children in the rainy season study and 928 children during the dry season
      survey for parasitologic tests. Their guardians provided information on water,
      sanitation, hygiene, and socioeconomic variables. The prevalence rates of G.
      intestinalis infection were 9.4% in the rainy season and 4.4% in the dry season.
      Higher rates of infection were observed in older individuals (9.5% and 10.6%) and
      girls had a lower risk of infection than boys (odds ratio [OR] =0.55, 95%
      confidence interval [CI] = 0.34, 0.88 in the rainy season and OR = 0.47, 95% CI =
      0.25, 0.90 in the dry season). During the wet season survey, a health risk was
      detected among those storing water in unprotected receptacles (OR = 4.00, 4.69,
      and 5.34 for those using uncovered jars, cisterns or tanks, and buckets,
      respectively), and bathing outside the dwelling, i.e., using a tap (OR = 1.93,
      95% CI = 1.10, 3.39). A health risk was also detected among children from
      households with unsafe food hygiene practices (OR =2.41, 95% CI =1.10, 5.30) and
      those with no hand-washing habits (OR = 2.27, 95% CI = 1.00, 5.20). Groundwater
      reserves are at risk of fecal pollution, as indicated by the presence of G.
      intestinalis cysts. However, the endemic pattern of intestinal infection reflects
      low standards of personal hygiene and unsafe drinking water storage and food
      related practices at household level. Prevention activities must address health
      education and environmental protection policies.

PMID- 15238692
TI  - Short report: Treatment failure due to mixed infection by different strains of
      the parasite Leishmania infantum.
AB  - Therapeutic failure in a human immunodeficiency virus-negative patient with
      visceral leishmaniasis was due to mixed infection by two different Leishmania
      infantum zymodemes: L. infantum zymodeme MON-98, which is a rare zymodeme and is
      reported for the first time in Greece, and zymodeme MON-1, which is common in the
      Mediterranean region. The two strains were isolated from two samples of bone
      marrow from the patient obtained before the administration of treatment and 20
      days later, since there was no improvement in the clinical signs. The zymodemes
      MON-98 and MON-1 exhibited different behaviors in vitro and showed different
      sensitivities to meglumine antimoniate in vitro and in vivo, as shown by clinical
      findings. Mixed infections with different Leishmania strains may explain the
      differences in the clinical course of leishmaniasis in many patients and may be
      the reason for treatment failures.

PMID- 15238693
TI  - Influence of breeding sites features on genetic differentiation of Aedes aegypti
      populations analyzed on a local scale in Phnom Penh Municipality of Cambodia.
AB  - This study analyzed genetic differentiation of 20 Aedes aegypti populations
      collected along a street in Phnom Penh Municipality of Cambodia. Using allozyme
      and microsatellite variations, we demonstrated that populations were
      differentiated and the pattern of differentiation was dependent on the type of
      breeding sites. Moreover, insecticide treatments with temephos mostly affect the
      population functioning of discarded containers. Low gene flow detected could
      limit the natural diffusion of resistant populations that might instead take
      advantage of human displacements to spread.

PMID- 15238694
TI  - Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from
      the Brazilian Amazon using skin tests.
AB  - Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be
      present in similar environments, there have been many epidemiologic
      investigations regarding the prevalences of these two organisms. However, cross
      reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this
      usually results in the overestimation of the prevalence of P. brasiliensis. The
      prevalence of infection with P. brasiliensis was evaluated in a cross-sectional
      study of 298 asymptomatic school children in the Brazilian Amazon region (Mato
      Grosso State). In this investigation, the reactivity of children to two different
      P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD
      glycoprotein (gp43), was compared with or without the co-administration of
      histoplasmin. In the group of individuals receiving paracoccidioidin who had a
      positive histoplasmin skin test result, the prevalence of exposure to P.
      brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was
      significantly higher than that observed in other groups, which ranged from 4% to
      6% (P < 5 x 10(-4) for each). Overall prevalence was 4.6% (95% confidence
      interval = 2.5-7.7%). These data suggest that gp43 provides a better estimate of
      exposure to P. brasiliensis when the co-administration of histoplasmin is
      desired.

PMID- 15238695
TI  - Cloning and characterization of a new cysteine proteinase secreted by Paragonimus
      westermani adult worms.
AB  - The cysteine proteinases of Paragonimus westermani are known to play important
      roles in invasion and pathogenesis to hosts and in immune modulation and nutrient
      uptake. In this study, we have cloned a new cysteine proteinase of P. westermani,
      PwCP2, from adult worms and tested its diagnostic usefulness. The PwCP2 gene had
      an open reading frame of 816 base pairs and a conserved catalytic triad of
      cysteine, histidine, and asparagine residues. The mature form of recombinant
      PwCP2 (rPwCP2) lacking a proregion was overexpressed in Escherichia coli and used
      to produce antiserum. Western blot and immunohistochemical analyses using this
      antiserum showed that PwCP2 was expressed as a mature form, 24-kD product in a
      crude extract and in the excretory-secretory product of P. westermani, and was
      localized mainly in the intestinal epithelium of the adult worm. Western blot
      analysis using the rPwCP2 showed not only high sensitivity (90%) and specificity
      (100%) to sera from patients with paragonimiasis westermani, but also no cross
      reactivity with sera from patients with clonorchiasis, sparganosis, or
      cysticercosis. Furthermore, an enzyme-linked immunosorbent assay using rPwCP2
      exhibited a sensitivity of 93% and a specificity of 93% with sera of rats
      infected with P. westermani metacercariae. These results suggest that the
      excretory-secretory PwCP2 can be used for the diagnosis of paragonimiasis.

PMID- 15238696
TI  - Prevalence of antibodies to spotted fever group rickettsiae in humans and
      domestic animals in a Brazilian spotted fever-endemic area in the state of Sao
      Paulo, Brazil: serologic evidence for infection by Rickettsia rickettsii and
      another spotted fever group Rickettsia.
AB  - In serum samples obtained from all the healthy humans, horses, dogs, and donkeys
      present on three farms in the Pedreira Municipality, an endemic area for
      Brazilian spotted fever, an indirect immunofluorescence assay (IFA) detected
      antibodies against Rickettsia rickettsii in 17 (77.3%) horses, 5 (31.3%) dogs
      (titers ranging from 64 to 4,048), and none of 4 donkeys or 50 humans. Five
      canine and eight equine sera with high antibody titers to R. rickettsii were also
      tested by IFA against R. bellii, R. akari, and R. africae antigens. Sera from two
      horses and two dogs that showed similar high antibody titers against two
      rickettsial antigens were evaluated after cross-absorption. Sera from seven
      horses and two dogs contained antibodies specific for R. rickettsii, and one dog
      serum had antibodies against a Rickettsia species very closely related to R.
      africae. The latter may have been caused by infection with the recently
      identified COOPERI strain.

PMID- 15238697
TI  - Diagnosis of urinary schistosomiasis: a novel approach to compare bladder
      pathology measured by ultrasound and three methods for hematuria detection.
AB  - We aggregated published data from field studies documenting prevalence of
      Schistosoma haematobium infection and bladder pathology determined by
      ultrasonography or hematuria detected by reagent strip, questionnaire, or visual
      examination. A mathematical expression was used to describe the associations
      between prevalence of pathology/morbidity and infection. This allows for indirect
      comparison of these methods, which are rarely used simultaneously. All four
      methods showed a similar, marked association with infection. Surprisingly,
      ultrasound revealed higher prevalences of pathology in schools than in
      communities with the same prevalence of infection, implying a need for age
      related cut-off values. Reagent strip testing yielded a higher prevalence than
      questionnaire, which in turn was higher than by visual examination. After
      correction for morbidity due to other causes, a consistent ratio in prevalence of
      hematuria of 3:2:1 resulted for the three respective methods. The simple
      questionnaire approach is not markedly inferior to the other techniques, making
      it the best option for field use.

PMID- 15238698
TI  - Association of a sex-related difference of Strongyloides stercoralis-specific
      IgG4 antibody titer with the efficacy of treatment of strongyloidiasis.
AB  - It is difficult to completely eradicate strongyloidiasis, a human intestinal
      nematode infection with Strongyloides stercoralis with drugs, especially in
      males. To find host factors involved in the response to treatment, patients
      infected with S. stercoralis were examined for S. stercoralis-specific antibody
      titers and the effect of treatment with albendazole on these titers were
      determined. The cure rate was slightly but not significantly lower in males than
      in females (P = 0.108). However, a significantly higher titer of S. stercoralis
      specific IgG4 antibody was observed in males than in females (P = 0.0097), and
      the S. stercoralis-specific IgG4 antibody titer was significantly higher in the
      male non-cured group than in the cured group (P = 0.035). These results suggest
      that elevation of the S. stercoralis-specific IgG4 antibody titer is associated
      with resistance to treatment of S. stercoralis infection, especially in males.

PMID- 15238699
TI  - Prevalence of West Nile virus in tree canopy-inhabiting Culex pipiens and
      associated mosquitoes.
AB  - Culex pipiens was the dominant mosquito captured in a West Nile virus (WNV) focus
      in Stratford, Connecticut. More Cx. pipiens were captured in Centers for Disease
      Control miniature light traps baited with CO(2), quail/hamster traps, and
      mosquito magnet experimental (MMX) traps placed in the tree canopy than in
      similar traps placed near the ground. Significantly more Cx. pipiens were
      captured in MMX traps placed in the canopy than in the other traps tested. Ninety
      two percent and 85% of the 206 and 68 WNV isolations were from Cx. pipiens in
      2002 and 2003, respectively; 5% and 12% were from Cx. salinarius. Eighty-five
      percent and 87% of the isolates were from mosquitoes captured in the canopy in
      each of the two years. The significantly larger numbers of WNV isolates from Cx.
      pipiens captured in the canopy are attributed to the significantly larger numbers
      of Cx. pipiens captured in the canopy in comparison to those captured in traps
      near the ground.

PMID- 15238700
TI  - Real-time reverse transcriptase-polymerase chain reaction quantification of West
      Nile virus transmitted by Culex pipiens quinquefasciatus.
AB  - Transmission experiments are a critical component of vector competence studies.
      In this study, a real-time reverse transcriptase-polymerase chain reaction (RT
      PCR) was used to enumerate the amount of West Nile virus (WNV) secreted in
      mosquito saliva following oral infection. Culex pipiens quinquefasciatus were
      allowed to feed on WNV-infected blood, and saliva was collected on days 14 and 21
      post-infection (pi). The amount of virus at these two time points varied
      significantly, with mean equivalent plaque-forming units (pfu) of approximately
      30,500 on day 14 pi and 5,800 on day 21 pi. Individual mosquitoes secreted up to
      2 x 10(5) pfu of virus. Titer of whole mosquitoes and immunofluorescence assay of
      salivary glands from mosquitoes collected at these two time points were also used
      for supplemental comparison. This report describes the first use of a real-time
      RT-PCR to quantify the amount of WNV in mosquito saliva.

PMID- 15238701
TI  - Lectin histochemistry of normal human gastric mucosa.
AB  - Information about the saccharides expressed in gastric mucosa is mostly limited
      to the glycan content of gastric mucins and there are only a few studies of the
      glycoprofiling of the constituent cells and their components. Knowledge of the
      glycan expression of normal gastric mucosa is necessary for the interpretation of
      the significance of changes of expression in disease. lectin histochemical study
      of normal human gastric (body) mucosa was performed using 27 lectins chosen to
      probe for a wide range of oligosaccharide sequences within several categories of
      glycoprotein glycans. here were marked differences in staining reactions in the
      various microanatomical structures of the mucosa, particularly between pits and
      glands with the former more closely resembling the surface epithelium. A notable
      feature was the degree of difference in the staining between a substantial sub
      population of cells within the neck region and the epithelium of both the pits
      and glands. These neck cells resembled the pit cells with some lectins, glandular
      cells with some others and neither with some other lectins. Overall, the
      differences between the pit, gland and neck epithelia were diverse and numerous,
      and could not be explained by altered activity of a small set of
      glycosyltransferases. Widespread alterations of glycans must have occurred
      (affecting terminal and internal parts of their structures) and the very
      different glycotypes of the pit, neck and gland epithelia are, therefore,
      suggestive of the existence of three cell lineages within normal gastric
      epithelium.

PMID- 15238702
TI  - Localization of sialidase-positive cells expressing Mac-1 and immunoglobulin in
      the mouse thymus.
AB  - We have sought an endogenous membrane bound sialidase acting at neutral pH in
      immune system, because the removal of sialic acid from cell surfaces will affect
      the cell-cell interaction directly or indirectly. The levels of activity of
      unique membrane-bound sialidase at neutral pH and also soluble sialidase are high
      in the thymus but low in the spleen and lymph nodes. These are thought to be
      plasma membrane and cytosolic types based on the behavior of inhibition by Cu(2+)
      and 2-deoxy-2, 3-dehydro-N-acetylneuraminic acid. Newly synthesized 5-bromo-4
      chloro-3-indolyl-N-acetylnueraminic acid was used for histochemical staining of
      sialidase-positive thymic cells, and the results showed positive cells sparsely
      distributed in the corticomedullar region or medullary region of the thymus. They
      expressed immunoglobulin and Mac-1 antigen on their surfaces. These cells must
      therefore be of a B cell lineage, not a T cell lineage. We also found that some
      vessels in the thymus were sialidase-positive.

PMID- 15238703
TI  - Monitoring of the tissue distribution of fibroblast growth factor containing a
      high mannose-type sugar chain produced in mutant yeast.
AB  - Most therapeutic glycoproteins have been produced in mammalian cell lines.
      However, the mammalian cell culture system has various disadvantages, i.e., a
      high culture cost, difficulty in performing a large scale-up because of
      complicated handling requirements, and the risk of contamination by prion or
      other unknown pathogenic components through cultivation in the presence of bovine
      serum. There is thus a growing need for other host cells in which the recombinant
      glycoproteins can be produced. Recently, we successfully developed a mutant yeast
      strain engineered in a glycosylation system. The sugar chain produced in the
      mutant yeast is not immunogenic to the human immuno-surveillance system. In the
      present study, we selected fibroblast growth factor (FGF) as a model glycoprotein
      and assessed the bioactivity of FGF produced in yeast in terms of its
      proliferating activity and tissue distribution in mammalian cells and in the
      whole body. Structural changes in the sugar chains of FGFs derived from mutant
      yeast, as compared with those from mammalian cells, did not affect the
      proliferating activity remarkably. However, the tissue distribution in the mouse
      differed significantly; a high-mannose type sugar chain was the major determinant
      of the specific distribution of FGF to the kidney. The mechanism of this
      phenomenon is still unclear, but our observations suggest that recombinant
      glycoproteins derived from mutant yeasts producing high-mannose type sugar chains
      would be applicable for tissue-targeting therapy.

PMID- 15238704
TI  - Alteration in N -acetylglucosaminyltransferase activities and glycan structure in
      tissue and bile glycoproteins from extrahepatic bile duct carcinoma.
AB  - The activities of three N -acetylglucosaminyltransferases (GnT)-III, IV and V, as
      well as the structural alterations of N-glycans on the glycoproteins in cancer
      tissues and bile specimens from 28 cases of extrahepatic bile duct carcinoma
      (EBDC) were compared with those from 18 cases of benign biliary duct diseases
      (BBDD). GnT activities were determined with fluorescence-labeled substrate using
      a HPLC method. It was found that GnT-III and GnT-V activities in EBDC were
      increased to 3.14 and 15.96 times respectively of the mean BBDD values, but GnT
      IV remained unchanged. The activity of GnT-V was correlated with the grade of
      differentiation and TMN stage of EBDC. The up-regulation of GnT-III resulted in
      the increased bisecting-GlcNAc on the N-glycans of glycoproteins in cancer
      tissues and a 201 kDa bile glycoprotein when analyzed with HRP-labeled E(4)-PHA.
      The increased GnT-V activity led to the elevation of the beta1,6GlcNAc branch (or
      antennary number) on the N-glycans in cancer tissue glycoproteins and 201, 163,
      122 kDa proteins in the bile as probed with HRP-labeled DSA. These findings
      suggest that the alteration in GnT activities may be involved in the malignant
      transformation and development of EBDC, resulting in the aberrant glycosylation
      of some tissue and bile proteins. The latter was expected to be used in the
      clinical diagnosis and prognosis evaluation in EBDC patients.

PMID- 15238743
TI  - Could your workplace environment improve?

PMID- 15238705
TI  - Preparation and immunological studies of protein conjugates of N -acylneuraminic
      acids.
AB  - The overexpression of N -acetylneuraminic acid (Neu5Ac) is closely correlated
      with malignant transformations. Thus, Neu5Ac is an important target in the design
      of cancer vaccines. To study the influence of chemical modifications of Neu5Ac on
      its immunological properties, the alpha-allyl glycosides of five differently N 
      acylated neuraminic acid derivatives were prepared. Following selective
      ozonolysis of their allyl group to form an aldehyde functionality, they were
      coupled to keyhole limpet hemocyanin (KLH) via reductive amination. Resultant
      glycoconjugates were studied in C57BL/6 mice. The N -propionyl, N - iso- butanoyl
      and N -phenylacetyl derivatives of neuraminic acid provoked robust immune
      responses of various antibody isotypes, including IgM, IgG1, IgG2a and IgG3,
      whereas N -trifluoropropionylneuraminic acid and natural Neu5Ac were essentially
      nonimmunogenic. Moreover, the N -phenylacetyl and N - iso- butanoyl derivatives
      mainly induced IgG responses that are desirable for antitumor applications. These
      results raise the promise of formulating effective glycoconjugate cancer vaccines
      via derivatizing sialic acid residues of sialooligosaccharides.

PMID- 15238744
TI  - Should learning Spanish be strongly encouraged in the undergraduate nursing
      curriculum? Writing for the pro position.

PMID- 15238745
TI  - Should learning Spanish be strongly encouraged in the undergraduate nursing
      curriculum? Writing for the con position.

PMID- 15238746
TI  - Working women's breastfeeding experiences.
AB  - PURPOSE: To describe the breastfeeding experiences of women who returned to work
      after childbirth. DESIGN AND METHODS: Descriptive, using questionnaires with 50
      women. Content analysis of data obtained from women who responded to open-ended
      questionnaires at 16 weeks postpartum. Three procedures were used: coding data,
      categorizing text units, and refining the emerging themes. RESULTS: Four
      categories emerged from the data:support, attitude, strategic plan, and
      psychological distress. The women expressed a need for support such as an
      accepting environment, spatial issues, modeling, and time allowance. They needed
      to maintain a positive attitude so they could commit to and accomplish their
      breastfeeding goals. The women developed strategic plans to help prevent
      breastfeeding problems as well as continue breastfeeding successfully. Finally,
      they described psychological distress as a conflict between the demands of work
      and the breastfeeding process. Associated feelings included guilt, stress, or
      having to sacrifice. CLINICAL IMPLICATIONS: These findings can help nurses and
      other healthcare professionals in providing anticipatory guidance to women who
      plan to continue breastfeeding after returning to work. Further research should
      investigate the relationship between psychological distress, work productivity,
      family functioning, and breastfeeding activities of working women who breastfeed.

PMID- 15238748
TI  - From the field: a maternal-child health nursing competence validation model.
AB  - This group of Vermont community health nurses from different agencies
      collaborated to develop a competence validation framework for maternal and child
      health nursing in the practice areas of perinatal client teaching, breastfeeding,
      and prenatal, postpartum, and newborn nursing care. The framework is based on the
      work of Benner, using the "competent" level of nursing practice, and delineates
      three parameters of competence: technical skills, interpersonal skills, and
      critical thinking skills. Learning resource materials, including newborn and
      maternal assessment guidelines, were developed for each competence area. The four
      competence validation tools were successfully tested for validity and reliability
      as well as efficiency and effectiveness by nurses in all 13 home health agencies
      and 12 public health district offices in Vermont. This system of competence
      validation is now used to support a consistently high quality of care for all
      recipients of Vermont's Healthy Babies, Kids, and Families services, and is
      available for use in other care settings.

PMID- 15238750
TI  - Breast augmentation & lactation outcome: a case report.
AB  - This article contains two case reports that illustrate the difficulty two mothers
      experienced when they mechanically expressed their milk for their very preterm
      infants. Each of the mothers was enrolled in a separate research study and had
      previously undergone surgery for breast augmentation. Neither of the mothers was
      able to provide an adequate milk supply for her preterm infant. Preoperative
      counseling and informed consent for breast augmentation is vital if the mother
      desires to exclusively provide mother's milk for the infant.

PMID- 15238751
TI  - Caring for a laboring woman with amyotrophic lateral sclerosis: a case report.
AB  - A case presentation of a pregnant 32-year-old woman with advanced amyotrophic
      lateral sclerosis who presented in labor at 38+6 weeks gestation is described.
      Amyotrophic lateral sclerosis is a progressive neuromuscular disease that attacks
      nerve cells in the brain and spinal cord. It is usually diagnosed after the
      fourth decade of life, and is more commonly seen in men than women; thus, it is
      rarely found in the obstetric population. When the perinatal team is confronted
      with a pregnant woman with ALS,patient management can be a challenge.

PMID- 15238752
TI  - Breastfeeding in chronic illness: the voices of women with fibromyalgia.
AB  - PURPOSE: To describe what it is like for women with fibromyalgia (FM) to
      breastfeed their infants. STUDY DESIGN AND METHODS: Nine women with FM who chose
      to breastfeed their infants were the sample for this qualitative study. van
      Manen's phenomenological method of reflection, writing, and rewriting was used to
      analyze the data collected through in-depth tape-recorded interviews and written
      stories. RESULTS: All nine women felt that they were not successful in their
      attempts to breastfeed, and felt frustrated. Themes included (a) muscle soreness,
      pain, and stiffness made it difficult to breastfeed the baby; (b) fatigue
      interfered with the breastfeeding process; (c) the need for medication, perceived
      insufficient milk supply, and sore nipples led to forced unplanned weaning; and
      (d) being forced to wean the infant when not ready to do so created sadness and a
      feeling of depression. CLINICAL IMPLICATIONS: Nurses who work with women with FM
      who choose to breastfeed need to be proactive in providing informational,
      emotional, and physical support to facilitate a successful breastfeeding
      experience for these women. Knowing that the pain, muscle soreness, stiffness,
      and fatigue of FM may affect breastfeeding can direct nurses to help women with
      FM plan for support after childbirth and learn techniques to control/reduce the
      muscle pain and stiffness. Nurses are encouraged to refer breastfeeding women
      with FM to lactation consultants and support groups for encouragement and
      validation regarding their concerns about breastfeeding. It is important that
      nurses continue to serve as advocates for breastfeeding women with FM and keep
      other healthcare providers informed about the issues related to breastfeeding for
      women with FM.

PMID- 15238753
TI  - Management of UTIs during pregnancy.
AB  - This article summarizes the pathophysiology, patient presentation, diagnostic
      testing, and current treatment modalities for pregnant women presenting with
      urinary tract symptoms in pregnancy. Urinary tract infection is a common health
      problem, affecting millions of people each year. However, this seemingly benign
      condition may have serious consequences if it occurs during the course of a
      woman's pregnancy, and if untreated could lead to pyelonephritis, preterm labor,
      or Group B Streptococcal infection in the newborn. Thus, the prevention, early
      detection, and prompt treatment of urinary tract infections in pregnancy have
      become essential components of prenatal care.

PMID- 15238754
TI  - Solids--when and why.

PMID- 15238755
TI  - Centering pregnancy: a renaissance in prenatal care?

PMID- 15238756
TI  - Perinatal patient safety.

PMID- 15238757
TI  - Physiological responses to circumcision.

PMID- 15238759
TI  - Pain management for infants.

PMID- 15238760
TI  - Culture and risk taking.

PMID- 15238762
TI  - Needed continuing education.

PMID- 15238765
TI  - Time out: it's time well spent.

PMID- 15238766
TI  - Tracking the killers: how should we measure CD8 T cells in HIV infection?

PMID- 15238767
TI  - Alleles of the gene encoding IL-1alpha may predict control of plasma viraemia in
      HIV-1 patients on highly active antiretroviral therapy.
AB  - OBJECTIVE: Some HIV patients treated with highly active antiretroviral therapy
      (HAART) do not resolve their plasma viraemia or HIV RNA can reappear after a
      period of virological control. We investigate whether polymorphisms in cytokine
      genes affect the control of plasma HIV RNA over 5 years on HAART. DESIGN: The
      study utilized adult HIV-infected patients in Western Australia. Plasma HIV-RNA
      levels were assessed from commencement of HAART in patients who had a CD4 T-cell
      count less than 100 cells/microl before HAART and achieved immune reconstitution
      assessed by CD4 T-cell counts. RESULTS: Control of plasma viraemia could be
      predicted from carriage of allele 2 at position -889 in the IL1A gene (IL1A
      889*2). This was significant when assessed by the proportion of patients with a
      plasma HIV-RNA level of 400 copies/ml or less (P = 0.002). At 48 months post
      HAART, proportions were approximately 0.76, 0.51 and 0.32 for IL1A (1,1), (1,2)
      and (2,2) patients, respectively. The outcome was independent of the patients'
      CD4 T-cell counts before or on therapy, drug regimen or age. Polymorphisms in
      IL6, TNFA, IL1B or IL12B had less significant effects, which became marginal when
      IL1A was included in the statistical model. IL1A-889 was in linkage
      disequilibrium with a non-synonymous polymorphism at IL1A+4845. CONCLUSION:
      Alleles carried at IL1A-889 or IL1A+4845 may predict the control of HIV
      replication in previously immunodeficient patients responding to HAART.

PMID- 15238768
TI  - Evolution of resistance to drugs in HIV-1-infected patients failing
      antiretroviral therapy.
AB  - BACKGROUND AND OBJECTIVE: The optimal time for changing failing antiretroviral
      therapy (ART) is not known. It involves balancing the risk of exhausting future
      treatment options against the risk of developing increased drug resistance. The
      frequency with which new drug-resistance mutations (DRM) developed and their
      potential consequences in patients continuing unchanged treatment despite
      persistent viremia were assessed. DESIGN: A retrospective study of consecutive
      sequence samples from 106 patients at one institution with viral load (VL) of
      more than 400 copies/ml, with no change in ART for more than 2 months despite
      virologic failure. METHODS: Two consecutive pol sequences, CD4 cell counts and VL
      were analyzed to quantify the development of new DRM and to identify changes in
      immunologic and virologic parameters. Genotypic susceptibility scores (GSS) and
      viral drug susceptibilities were calculated by a computer program (HIVDB).
      Poisson log-linear regression models were used to predict the expected number of
      mutations at the second time point. RESULTS: : After a median of 14 months of
      continued ART, 75% (80 of 106) of patients acquired new DRM and were assigned a
      significantly lower GSS, potentially limiting the success of future ART. The
      development of new DRM was proportional to the time between the two sequences and
      inversely proportional to the number of DRM in the first sequence. However, the
      development of DRM was not associated with significant changes in CD4 or VL
      counts. CONCLUSIONS: Despite stable levels of CD4 and VL over time, maintaining a
      failing therapeutic regimen increases drug resistance and may limit future
      treatment options.

PMID- 15238769
TI  - HIV-1 superinfection and viral diversity.
AB  - OBJECTIVE: Sequential acquisition of viral variants, or HIV-1 superinfection, has
      been proposed to explain the high fractions of recombinant viruses observed in
      some geographical regions, but only a few cases of superinfection in humans have
      been reported. Animal models suggest that susceptibility to superinfection may be
      restricted to a short period of time after initial infection, possibly due to
      maturation of broad antiviral immune responses. METHODS: A mathematical model
      involving a system of differential equations was developed to identify
      transmission and superinfection patterns that would lead to the observed global
      patterns of viral diversity. RESULTS: Requirements for a high prevalence of
      infections involving recombinant viruses include high viral infectivity, the
      presence of highly sexually active core groups, and introduction of divergent
      viruses early in the epidemic spread of HIV-1. Restricted superinfection could
      explain the persistent predominance of single virus subtypes in regions with well
      established HIV-1 epidemics. The rate of recombination within individuals was not
      strongly related to recombinant fractions in populations. CONCLUSIONS: HIV-1
      superinfection restricted to early HIV-1 infection could account for the high
      fraction of recombinant virus infections observed in populations. The
      relationship between recombination in cellular infections and recombinant
      fractions in populations is complex and depends on epidemiological factors and
      biological factors that can be modeled.

PMID- 15238770
TI  - The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive
      patients: a case-control study.
AB  - OBJECTIVE: Pancreatic disorders in HIV-positive patients are frequent. CFTR and
      SPINK-1 mutations have been reported to increase the risk of pancreatitis, but no
      data are available in HIV-positive patients. This study will evaluate the
      frequency of CFTR mutations and SPINK-1 polymorphisms in HIV-positive patients
      with clinical pancreatitis or asymptomatic elevation of serum pancreatic enzymes.
      METHOD: Cases (patients with hyperamylasemia) were identified during a toxicity
      study conducted in August 1999 among 1152 participants of the Swiss HIV Cohort
      Study. We designed a case-control study in which each case was matched one to one
      to an HIV-infected control according to sex, age, CD4 cell count, viraemia and
      medication use. CFTR mutations and SPINK-1 polymorphisms were studied using
      polymerase chain reaction techniques. RESULTS: Fifty-one HIV-positive patients
      with hyperamylasemia were detected among 1152 participants in the toxicity study
      (4.4%). There were 13 carriers of CFTR and SPINK-1 mutations (12.7%). Amylase
      levels were 316 +/- 130 U/l for the group with mutations, and 135 +/- 18 U/l for
      non-carriers (P = 0.79). However, among patients with hyperamylasemia, those with
      CFTR or SPINK-1 mutations had 648 +/- 216 U/l amylase levels compared with 232 +/
      28 U/l for those without (P = 0.025). Ten patients had acute pancreatitis, four
      of whom had CFTR mutations or SPINK-1 polymorphisms (40%) compared with seven of
      the control patients (14%) (P = 0.01). CONCLUSION: CFTR mutations and SPINK-1
      polymorphisms are frequent among HIV-positive patients suffering from acute
      pancreatitis. These mutations may increase the susceptibility to pancreatitis
      when exposed to environmental risk factors.

PMID- 15238771
TI  - SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir
      /ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients.
AB  - OBJECTIVE: To compare the magnitude and durability of the antiviral response to
      fosamprenavir (FPV) plus ritonavir (RTV) once-daily (FPV/r QD) with nelfinavir
      twice-daily (NFV BID), each administered with abacavir and lamivudine twice
      daily. METHODS: An international, phase III, randomized, open-label study in
      antiretroviral therapy-naive, HIV-infected adults. RESULTS: Patients with
      advanced HIV disease received FPV/r QD (n = 322) or NFV BID (n = 327). At week
      48, 69% of patients in the FPV/r QD group and 68% in the NFV BID group had plasma
      HIV-1 RNA (vRNA) < 400 copies/ml, whereas 55% of patients in the FPV/r QD group
      and 53% in the NFV BID group had vRNA < 50 copies/ml (intent to treat,
      rebound/discontinuation = failure). More patients in the NFV BID group (17%)
      experienced virological failure than in the FPV/r QD group (7%). Efficacy of
      FPV/r QD was maintained in patients with CD4+ cell counts < 50 x 10 cells/l or
      vRNA >/= 100 000 copies/ml at entry. At week 48, median CD4+ cell counts were
      increased to 203 x 10 cells/l (FPV/r QD group) and 207 x 10 cells/l (NFV BID
      group). Both regimens were generally well tolerated. Diarrhea was more common on
      NFV BID than on FPV/r QD (16 versus 9%; P = 0.008). Fasting lipid profile results
      were generally favorable in both treatment arms. FPV/r QD maintained plasma
      amprenavir (APV) trough concentrations above the mean phenotypic drug
      susceptibility (IC50) for wild-type virus for APV. CONCLUSION: As a first choice
      protease inhibitor with a low daily pill burden, FPV/r QD was well tolerated and
      provided potent, durable antiviral suppression.

PMID- 15238772
TI  - Relationship between drug resistance and HIV-1 disease progression or death in
      patients undergoing resistance testing.
AB  - OBJECTIVE: To evaluate factors associated with drug resistance detected by
      genotypic antiretroviral resistance testing (GART), and to determine the
      association between the level of resistance and subsequent human immunodeficiency
      type 1 (HIV-1) disease progression or death. DESIGN: Observational cohort study.
      METHODS: We identified highly active antiretroviral therapy (HAART)-treated
      patients who had GART as part of clinical management. Factors associated with
      greater numbers of resistance mutations were assessed by ordinal logistic
      regression. Survival analysis was used to assess time to a new opportunistic
      condition or death following GART. RESULTS: A total of 572 patients were
      identified who had GART: of these, 50% had 0-2 resistance mutations, 33% had 3-6
      mutations, and 17% had >/= 7 mutations. In multivariate analysis, prolonged use
      of HAART in the setting of incomplete viral suppression was significantly
      associated with more drug resistance. Patients with fewer resistance mutations
      were significantly more likely to achieve viral suppression after GART than
      patients with more mutations. Compared to patients with two or less resistance
      mutations, those with three to six mutations, or seven or more mutations were not
      at higher risk of HIV-1 disease progression or death over a median follow-up of
      15 months. In contrast, continued HAART use following GART was strongly
      associated with slower disease progression, particularly at lower CD4 cell
      counts. CONCLUSION: These results support the hypothesis the drug-resistant HIV-1
      may be less pathogenic than wild-type virus, and that continued use of HAART
      might provide clinical benefit, despite persistent viremia and HIV-1 drug
      resistance.

PMID- 15238773
TI  - Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated
      antiretroviral toxic neuropathy.
AB  - BACKGROUND: Nucleoside analogue reverse transcriptase inhibitors (NRTI) disrupt
      neuronal mitochondrial DNA synthesis, impairing energy metabolism and resulting
      in a distal symmetrical polyneuropathy (DSP), an antiretroviral toxic neuropathy
      (ATN) that causes significant morbidity in HIV disease. Serum acetyl-l-carnitine
      (ALCAR) levels are decreased in neuropathy associated with NRTI therapy. ALCAR
      enhances neurotrophic support of sensory neurons and promotes energy metabolism,
      potentially causing nerve regeneration and symptom relief. OBJECTIVE: To assess
      the efficacy of oral ALCAR (1500 mg twice daily) for up to 33 months in an open
      cohort of 21 HIV-positive patients with established ATN. METHODS: Skin biopsies
      were excised from the leg before ALCAR treatment, at 6-12 month intervals
      thereafter and from HIV-negative non-neuropathic controls. Fibre types in
      epidermal, dermal and sweat gland innervation were quantified
      immunohistochemically. RESULTS: After 6 month's treatment, mean immunostaining
      area for small sensory fibres increased (epidermis 100%, P = 0.006; dermis 133%,
      P < 0.05) by more than that for all fibre types (epidermis 16%, P = 0.04; dermis
      49%, P < 0.05; sweat glands 60%, P < 0.001) or for sympathetic fibres (sweat
      glands 41%, P < 0.0003). Compared with controls, epidermal, dermal and sweat
      gland innervation reached 92%, 80% and 69%, respectively, after 6 month's
      treatment. Innervation improvements continued (epidermis and dermis) or
      stabilized (sweat glands) after 24 month's treatment. Neuropathic grade improved
      in 76% of patients and remained unchanged in 19%. HIV RNA load, CD4 and CD8 cell
      counts did not alter significantly throughout the study. CONCLUSIONS: ALCAR
      treatment improves symptoms, causes peripheral nerve regeneration and is proposed
      as a pathogenesis-based treatment for DSP.

PMID- 15238774
TI  - Anal carcinoma: incidence and effect of cumulative infections.
AB  - INTRODUCTION: Human papilloma virus (HPV) causes anal condyloma that is a risk
      factor for anal carcinoma. The incidence and mechanism of invasive anal carcinoma
      in patients with anal condyloma are prospectively determined. PATIENTS AND
      METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with anal
      canal condylomas were included in the study, after curing of their lesions. They
      were asked to attend follow-up visits at 3- or 6-month intervals. We checked for
      anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus,
      cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells
      (LC) in anal mucosa at baseline and during follow up. We cured and analysed
      relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads
      and CD4 T-lymphocyte counts were determined at each visit and the densities of LC
      in consecutive specimens from patients with cancers were compared with that for a
      matched control group (n = 23). RESULTS: Analysis of 199 patients showed high
      grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in
      HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV
      positive) patients developed invasive carcinoma after 13-108 months and 112 (56%)
      patients relapsed condylomas. HIV and anal co-infection were identified as
      independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence
      interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in
      anal mucosa were lower in patients with invasive carcinoma than in controls.
      CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased
      by HIV and anal co-infection. Decreases in LC numbers in anal mucosa may favour
      this outcome.

PMID- 15238775
TI  - Declining trend in transmission of drug-resistant HIV-1 in Amsterdam.
AB  - OBJECTIVE: Symptomatic primary HIV infections are over-represented in the mainly
      hospital-based studies on transmission of resistant HIV-1. We examined a more
      general population for the prevalence of resistant HIV-1 strains among primary
      infections. DESIGN: From 1994 to 2002 primary infections were identified within
      the Amsterdam Cohort Studies (ACS) among homosexual men and drug users, and at
      the Academic Medical Center (AMC). Whereas primary HIV-1-infected AMC patients,
      often presented with symptoms of acute retroviral syndrome, ACS participants
      largely seroconverted during follow-up and thus brought also asymptomatic primary
      infections to our study. METHODS: Reverse transcriptase (RT) and protease
      sequences were obtained by population-based nucleotide sequence analysis of the
      first HIV RNA-positive sample available. Subtypes were identified by phylogenetic
      analysis. Mutations were identified based on the IAS-USA resistance table.
      RESULTS: A total of 100 primary HIV-1 infections were identified (32 AMC and 68
      ACS). Transmission of drug-resistant strains decreased over calendar time, with
      20% [95% confidence interval (CI), 10-34%] of infections bearing drug-resistant
      mutations before 1998 versus only 6% (95% CI, 1-17%) after 1998. No multi-drug
      resistance pattern was observed. The median plasma HIV-1 RNA level of the first
      RNA positive sample was significantly lower for the individuals infected with a
      resistant strain versus those infected with wild-type, suggesting a fitness-cost
      to resistance. Four of seven non-B subtypes corresponded with the prevalent
      subtype in the presumed country of infection, and none showed resistance
      mutations. CONCLUSIONS: The transmission of drug-resistant HIV-1 strains in
      Amsterdam has decreased over time. Monitoring should be continued as this trend
      might change.

PMID- 15238776
TI  - Effect of discontinuing antiretroviral therapy on survival of women initiated on
      highly active antiretroviral therapy.
AB  - OBJECTIVE: To estimate the effect of discontinuing antiretroviral therapy (ART)
      on survival, among women who initiated highly active antiretroviral therapy
      (HAART). DESIGN: A multicenter cohort study. METHODS: A total of 951 HAART
      initiated women were followed for total mortality between 1995 and 2002. The
      relative hazard (RH) of death attributable to discontinuing all ART was estimated
      using an inverse probability of treatment-weighted marginal structural Cox
      proportional hazards model, as well as standard Cox models. RESULTS: Three
      hundred and forty-three out of 951 women discontinued all ART during the 3187
      person-years of follow-up, and 116 died. The RH of death attributable to
      discontinuation was 1.97 [95% confidence interval (CI) 1.17, 3.31] from the
      marginal structural Cox model. A RH of 1.49 (95% CI 0.94, 2.35) was observed
      using the same set of covariates in a standard Cox model. CONCLUSION: An
      increased risk of mortality for those HAART initiators who discontinued ART was
      observed using a marginal structural Cox model. This increased risk was
      independent of measured treatment failure, and was greatly attenuated in a
      standard Cox model with time-varying covariates.

PMID- 15238777
TI  - The impact of adult mortality on household dissolution and migration in rural
      South Africa.
AB  - OBJECTIVE: To investigate the effect of adult death on household dissolution and
      migration. DESIGN: Demographic surveillance of the population in a rural area of
      northern KwaZulu Natal, South Africa. METHODS: Data on households resident in the
      surveillance area on 1 January 2000 were used to examine the effect of adult
      mortality and household risk factors on household dissolution and mobility
      between January 2000 and October 2002. Cox regression models were used to assess
      the risk of household dissolution and migration, controlling for multiple risk
      factors including causes of death, household composition and household assets.
      RESULTS: By October 2002, 238 households (2%) had dissolved and 874 (8%) migrated
      out of the area; 21% (2179) of all households had at least one adult death (18
      years and older). Households where one or more adult members died during the
      follow-up period were four times more likely to dissolve, after controlling for
      household and community level risk factors [4.3; 95% confidence interval, (CI),
      3.3-5.7]. The risk of dissolution was significantly higher in households with
      multiple deaths (2.3; 95% CI, 1.3-4.3). There were no significant differential
      risks associated with cause of death, age or sex of the deceased. Adult mortality
      in the household was not associated with migration. CONCLUSIONS: Poorer
      households, as measured by asset ownership, and households trying to cope with
      adult deaths are vulnerable to dissolution. The dramatic increase in adult
      mortality attributable to AIDS will increase the number of households that do not
      survive as a functional and cohesive social group.

PMID- 15238778
TI  - The puzzle of genes and environmental risk factors for disease susceptibility:
      putting the pieces together.

PMID- 15238779
TI  - Screening for HIV-specific T-cell responses using overlapping 15-mer peptide
      pools or optimized epitopes.
AB  - The IFN-y enzyme-linked immunospot (ELI-Spot) assay is often used to map HIV
      specific CD8 T-cell responses. We compared overlapping 15-mer pools with
      optimized CD8 epitopes to screen ELISpot responses in HIV-infected individuals.
      The 15-mer pools detected responses to previously undefined epitopes, but often
      missed low-level responses to predefined epitopes, particularly when the epitope
      was central in the 15-mer, rather than at the N-terminus or C-terminus. These
      factors should be considered in the monitoring of HIV vaccine trials.

PMID- 15238780
TI  - A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated
      with HIV-1 infection in Italian children.
AB  - In this study we show a significant correlation between a single-nucleotide
      polymorphism in the 5'-untranslated region of the DEFB1 gene, which probably
      regulates the gene expression of human beta defensin 1 (hBD-1) and the risk of
      HIV-1 infection in an Italian paediatric population (97 HIV-1 perinatally
      infected children), pointing to the importance of innate immunity in HIV-1
      infection.

PMID- 15238781
TI  - The prostate as a reservoir for HIV-1.
AB  - As the prostate can harbor bacterial and fungal pathogens, it was investigated as
      a reservoir for HIV. Nine men chronically infected with HIV participated in a
      crossover trial in which weekly semen samples were collected with and without
      previous prostate massage (PM). Six of the nine participants had undetectable
      seminal plasma(SP) HIV RNA in all samples without previous PM, but had detectable
      SP HIV RNA (> 25 copies/ml) in one to three samples collected after PM.

PMID- 15238782
TI  - Liver fibrosis stage predicts early treatment outcomes with peginterferon plus
      ribavirin in HIV/hepatitis C virus co-infected patients.
AB  - Thirty-six HIV-infected patients with chronic hepatitis C treated with
      peginterferon alpha-2a or 2b plus ribavirin were analysed in a prospective
      observational study. The were 15 (42%) treatment discontinuations; bt intent-to
      treat virological responders were 19 (53%) at week 24. A higher fibrosis score
      predicted premature discontinuation of hepatitis C virus (HCV) therapy and a lack
      of early virological response. Female sex and HCV genotype predicted early
      virological responses. Results support the early treatment of HCV in co-infected
      individuals.

PMID- 15238783
TI  - The bisexual bridge revisited: sexual risk behavior among men who have sex with
      men and women, San Francisco, 1998-2003.
AB  - From 1998 to 2003 in San Francisco, unprotected anal intercourse (UAI) with one
      or more partner of unknown HIV serostatus (potentially serodiscordant UAI)
      increased among bisexual men who have sex with men (MSM) in parallel and in
      magnitude compared with other MSM. Potentially serodiscordant UAI and unprotected
      vaginal intercourse increased from 1998 to 2001 then decreased from 2001 to 2003.
      Although elements of a 'bisexual bridge' are present, we note an encouraging
      decrease in risk from 2001 to 2003.

PMID- 15238784
TI  - HIV-1 seroreversion in an HIV-1-seropositive patient treated during acute
      infection with highly active antiretroviral therapy and mycophenolate mofetil.

PMID- 15238785
TI  - Expansion of CD4+CD45RO+CD25- T cells in HIV-1 disease reflects an aspect of
      pathogenesis distinct from viral burden.

PMID- 15238787
TI  - Nail, hair and skin hyperpigmentation associated with indinavir therapy.

PMID- 15238786
TI  - Acute hepatic cytolysis in an HIV-infected patient taking atazanavir.

PMID- 15238788
TI  - Haemolytic anaemia after nucleotide antiretroviral treatment discontinuation in a
      chronic hepatitis B-virus co-infected AIDS patient.

PMID- 15238790
TI  - Immediate allergic reactions to betalactams: facts and controversies.
AB  - PURPOSE OF REVIEW: To analyse the available data in the field of immediate
      allergic reactions to beta-lactams, with particular emphasis on more recent
      studies, and to comment on the future role of this group of antibiotics. RECENT
      FINDINGS: The world of beta-lactams has become more complex than initially
      thought, due to the increased number of chemical structures available, the wide
      variety of indications for their use in treating different infectious diseases,
      and possibly also due to the interaction of other as yet undetermined factors.
      Benzyl penicillin, the original inducer of allergic reactions, has now largely
      been replaced by amoxicillin and, to a lesser extent, by cephalosporins in
      inducing IgE-mediated allergic reactions. These structures often share extensive
      cross-reactivity, eliciting clinical reactions to many compounds, especially
      amongst penicillins. In other circumstances selective responses are observed
      which are restricted to one group or one single compound, as occurs in the group
      of cephalosporins. The application of new determinants for skin testing and the
      use of adapted in-vitro studies have enabled these findings to be confirmed in
      detail. SUMMARY: Results indicate that evaluation of immediate reactions to beta
      lactams requires the use of several determinants for both in-vitro and in-vivo
      testing, and which must reflect the relevant drug involved in eliciting the
      response. This tendency will be strengthened in the future if use of benzyl
      penicillin continues to decrease as a drug to which populations are exposed.

PMID- 15238791
TI  - Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights
      into mechanisms and management.
AB  - PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors are widely prescribed
      for hypertension and heart failure. These drugs are commonly associated with
      cough, and are less commonly associated with angioedema, which may be potentially
      life threatening. This review describes data that extend our understanding of the
      mechanisms of these reactions, and provides guidance about clinical management.
      RECENT FINDINGS: For patients who develop angioedema from angiotensin-converting
      enzyme inhibitors, recent data are reassuring that the majority of such patients
      can tolerate angiotensin-II receptor blockers. These data support earlier
      conclusions that most patients with angiotensin-converting enzyme inhibitor
      induced cough can tolerate angiotensin-II receptor blockers. Limited case reports
      suggest that in acute angioedema induced by angiotensin-converting enzyme
      inhibitors, patients refractory to standard treatment may benefit from the
      infusion of fresh frozen plasma. SUMMARY: Although data are incomplete, it
      appears that angiotensin-converting enzyme inhibitors cause cough and angioedema
      through a cascade of effects that begins with the accumulation of kinins, and
      then involves arachidonic acid metabolism and nitric oxide generation. Most
      patients who develop either cough or angioedema from angiotensin-converting
      enzyme inhibitors can tolerate angiotensin-II receptor blocking agents.

PMID- 15238792
TI  - Smallpox, vaccination and adverse reactions to smallpox vaccine.
AB  - PURPOSE OF REVIEW: Public fear of the reintroduction of smallpox as a biological
      weapon or agent of bioterrorism has led to a renaissance of interest in smallpox,
      and a military and public health vaccination programme in the USA. Clinical
      experience from the last century together with novel immunobiological findings is
      the basis for current knowledge on smallpox as a disease. Pre-existing knowledge
      on smallpox vaccination, plus recent vaccination campaign-derived data, is the
      basis of current risk-benefit assessments. This article summarizes, from a
      dermatologist's point of view, current aspects of smallpox, smallpox vaccination
      and adverse reactions to vaccinia, the live virus smallpox vaccine. RECENT
      FINDINGS: The smallpox vaccination campaign in the USA has involved over 600,000
      vaccinees, and has largely confirmed incidence data on complications. An
      increased rate of myopericarditis is the new finding in the current vaccination
      campaign. Immunodeficiencies, manifest atopic dermatitis lesions and a history of
      atopic dermatitis remain contraindications to vaccination. Plasmacytoid dendritic
      cells are a key regulator of the human antiviral immune response and are
      recruited to inflamed skin in many skin diseases, but are depleted in atopic
      dermatitis lesions. The lack of plasmacytoid dendritic cell recruitment, together
      with the missing upregulation of antiviral peptides such as cathelicidin LL37 in
      atopic dermatitis lesions, is considered relevant for an atopic dermatitis
      patient's susceptibility to eczema vaccinatum. SUMMARY: Recent experience from
      the US smallpox vaccination campaign has largely confirmed what was known in the
      1960s. Current immunobiological research will enhance our understanding of the
      interaction between poxviruses and the skin's immune system.

PMID- 15238794
TI  - Anaphylaxis: can we tell who is at risk of a fatal reaction?
AB  - PURPOSE OF REVIEW: Anaphylaxis is frightening and patients commonly fear their
      next reaction will be fatal. This review looks at the characteristics of fatal
      reactions to find if a fatal recurrence is predictable. RECENT FINDINGS: Most
      publications on fatal anaphylaxis are case reports that do not help predict
      risks. Most epidemiological studies focus on non-fatal reactions. The UK fatal
      anaphylaxis register demonstrates that over two-thirds of those dying from sting
      reactions and over four-fifths dying from drug anaphylaxis had no previous
      indication of their allergy, whereas those dying from food allergy had usually
      had previous reactions but these were typically not severe. Recent reports of
      anaphylaxis epidemiology based on diagnostic coding or attendance for treatment
      may be biased by differences in health service resource utilization according to
      the cause and course of the reaction. SUMMARY: Most fatal anaphylactic reactions
      are unpredictable. The appropriate management after recovery from a severe
      reaction may be protective against a fatal recurrence. An accurate identification
      of the cause and effective avoidance is a crucial part of this management,
      together with effective treatment of asthma for those with food allergy,
      immunotherapy for sting allergy, the avoidance of drugs that potentiate
      anaphylaxis, and effective training in self-treatment.

PMID- 15238793
TI  - Adverse reactions to biological modifiers.
AB  - PURPOSE OF REVIEW: Newer biologic immunomodulators such as interferons, tumor
      necrosis factor alpha (TNFalpha) inhibitors, and monoclonal antibodies have been
      introduced into the management of various inflammatory conditions. This review
      addresses adverse responses to these agents. RECENT FINDINGS: Both interferon
      alpha and interferon-beta have been associated with autoimmune phenomena. The
      ability of TNFalpha antagonists to cause significant adverse reactions appears to
      be substantial. These are either related to interference with TNFalpha activity
      or as consequence of the agents, either immunoglobulin or fusion protein, being
      recognized as foreign proteins, becoming themselves targets of an immune
      response. SUMMARY: Although advancing the management of inflammatory conditions,
      biologic modifiers are attended by significant concerns. Identification of at
      risk groups and careful selection of appropriate patients will minimize
      occurrence of adverse events.

PMID- 15238795
TI  - Mastocytosis and Hymenoptera allergy.
AB  - PURPOSE OF REVIEW: Mastocytosis is a rare disease with associations with
      anaphylactic reactions to Hymenoptera stings. The purpose of this review is to
      examine these associations with regard to prevalence, diagnosis, treatment and
      prognosis in the insect-venom-allergic population. RECENT FINDINGS: Systemic
      mastocytosis is overrepresented in the Hymenoptera-allergic population and is
      associated with an increased risk of more-severe reactions following field stings
      or sting challenges, lack of sensitization to venoms by skin test or
      radioallergosorbent test, increased side effects to venom immunotherapy, reduced
      efficacy of venom immunotherapy and treatment failures. Serum tryptase
      determinations are a simple and reliable screening procedure for systemic
      mastocytosis. Patients with elevated values should be referred to specialized
      centers for confirmatory diagnosis including bone marrow histology. SUMMARY: The
      diagnosis of systemic mastocytosis should be considered in Hymenoptera-allergic
      patients showing any of the management problems associated with this disease.
      Patients with mastocytosis and Hymenoptera allergy require special attention,
      mainly because of reduced safety and efficacy of venom immunotherapy. Whether or
      not venom immunotherapy is given, such patients should continue to carry an
      Epipen indefinitely.

PMID- 15238796
TI  - Diagnostic methods for insect sting allergy.
AB  - PURPOSE OF REVIEW: This review overviews advances from mid-2002 to the present in
      the validation and performance methods used in the diagnosis of Hymenoptera venom
      induced immediate-type hypersensitivity. RECENT FINDINGS: The general diagnostic
      algorithm for insect sting allergy is initially discussed with an examination of
      the AAAAI's 2003 revised practice parameter guidelines. Changes as a result of a
      greater recognition of skin test negative systemic reactors include repeat
      analysis of all testing and acceptance of serology as a complementary diagnostic
      test to the skin test. Original data examining concordance of venom-specific IgE
      results produced by the second-generation Pharmacia CAP System with the Johns
      Hopkins University radioallergosorbent test are presented. Diagnostic performance
      of honeybee venom-specific IgE assays used in clinical laboratories in North
      America is discussed using data from the Diagnostic Allergy Proficiency Survey
      conducted by the College of American Pathologists. Validity of venom-specific IgE
      antibody in postmortem blood specimens is demonstrated. The utility of
      alternative in-vivo (provocation) and in-vitro (basophil-based) diagnostic
      testing methods is critiqued. SUMMARY: This overview supports the following
      conclusions. Improved practice parameter guidelines include serology and skin
      test as complementary in supporting a positive clinical history during the
      diagnostic process. Data are provided which support the analytical performance of
      commercially available venom-specific IgE antibody serology-based assays.
      Intentional sting challenge in-vivo provocation, in-vitro basophil flow cytometry
      (CD63, CD203c) based assays, and in-vitro basophil histamine and
      sulfidoleukotriene release assays have their utility in the study of difficult
      diagnostic cases, but their use will remain as supplementary, secondary
      diagnostic tests.

PMID- 15238797
TI  - Venom immunotherapy: adverse reactions and treatment failure.
AB  - PURPOSE OF REVIEW: Side effects of venom immunotherapy and lack of efficacy
      represent significant problems in the treatment of patients allergic to
      Hymenoptera venom. Among these side effects systemic anaphylactic reactions and
      large local reactions are the most important. This review aims to discuss new
      insights in frequency, pathogenesis and handling of these common side effects and
      of treatment failure during venom immunotherapy. RECENT FINDINGS: Several studies
      showed that severe side effects due to venom immunotherapy are rare. Recently
      published studies focus on ultrarush protocols and report good tolerance of an
      ultrarush venom immunotherapy in which the maintenance dose was reached within
      several hours or 2 days, respectively. Compared to the use of aqueous extracts
      (administered according to a rush protocol), frequency of local and also systemic
      side effects was lower when depot extracts and schedules with a slow conventional
      dose increase were applied. Concomitant treatment with H1-antihistamines was
      found to reduce local and mild systemic adverse reactions during venom
      immunotherapy. Up to 25% of patients are not protected when re-stung while on
      venom immunotherapy with the usual maintenance dose of 100 microg of venom every
      4-8 weeks. These patients can achieve full protection by increasing the
      maintenance dose. SUMMARY: Conventional dose increase using depot extracts is
      better tolerated than if aqueous extracts are being administered. Concomitant
      treatment with H1-antihistamines may be helpful. Increasing the venom dose to 200
      microg or even more may be therapeutically effective in patients not protected by
      a lower maintenance dose. To compare tolerance of different treatment protocols
      prospective comparative studies are required.

PMID- 15238798
TI  - Mechanisms of immunotherapy: IgG revisited.
AB  - PURPOSE OF REVIEW: This paper will review historical and recent evidence for the
      induction of 'blocking' IgG antibodies during successful specific immunotherapy.
      RECENT FINDINGS: Specific immunotherapy is frequently associated with a rise in
      allergen-specific IgG4 antibodies and a modest reduction in specific IgE titres,
      although this does not always correlate with clinical efficacy. There is
      accumulating evidence that specific immunotherapy also influences the blocking
      activity on IgE-mediated responses by IgG4, and cellular assays are commonly used
      to investigate these changes. Recently, a novel assay, which detects allergen-IgE
      binding using flow cytometry, has been used to detect 'functional' specific
      immunotherapy-induced changes in IgG antibody activity. Results suggest that
      successful specific immunotherapy is associated with an increase in IgG blocking
      activity that is not solely dependent on the quantity of IgG antibodies. SUMMARY:
      Successful immunotherapy is associated with quantitative and qualitative changes
      in the allergen-specific IgG antibody response. The induction of IgG antibodies
      with blocking activity may have a protective role not only through the inhibition
      of allergen-induced, IgE-mediated release of inflammatory mediators from mast
      cells and basophils, but also through the inhibition of IgE-facilitated antigen
      presentation to T cells. Qualitative changes in the allergen-specific IgG
      antibody response may possibly be an important mechanism underlying the clinical
      efficacy of specific immunotherapy. Monitoring changes in blocking activity using
      cellular assays may give an early indication of the potential success of
      treatment.

PMID- 15238799
TI  - Distribution of vespid species in Europe.
AB  - PURPOSE OF REVIEW: Knowledge of the different stinging vespids found in various
      parts of Europe and their venom cross-reactivity is important in order to improve
      the venoms available for diagnostic and therapeutic purposes. RECENT FINDINGS: In
      recent years the amino acid sequences of different vespid venom allergens have
      been determined. Comparison of these sequences has led to an improved taxonomical
      classification of vespids compared with that based on morphological differences.
      However, the distribution of vespids in Europe is still based on a very good but
      somewhat old study carried out in the 1970s. Most recent epidemiological studies
      focus on the type of reaction produced rather than the insect responsible.
      SUMMARY: The genera Vespula, Dolichovespula and Vespa are found all over Europe,
      but the genus Polistes, although present in central Europe, is not found in the
      UK and only represents a specific clinical problem in areas around the
      Mediterranean sea. Although there are significant differences in the distribution
      of stings, the genus Vespula predominates over Polistes and Vespa throughout
      Europe, except in Mediterranean areas. The different species of Polistes in
      Europe show a great similarity in the sequences of their venom allergens, but the
      similarity to their American counterparts is less marked. Vespula allergens show
      up to 95% sequence identity and almost complete cross-reactivity. There is also
      great cross-reactivity among the genera Vespula, Vespa and Dolichovespula. This
      identity of amino acid sequences confirms the latest morphological taxonomy of
      Hymenoptera and opens the way for the use of recombinant hybrids of different
      species in venom immunotherapy.

PMID- 15238800
TI  - Ant allergy in Asia and Australia.
AB  - PURPOSE OF REVIEW: Anaphylaxis due to ant sting is increasingly being recognized
      as a significant problem. Severe allergic reactions to ants are well described in
      the south-eastern United States, but have only been recognized in recent years as
      being important in other parts of the world. There are many different ant species
      and their distribution around the world varies. The purpose of this review is to
      familiarize the reader with the epidemiology and clinical characteristics of ant
      allergy in Asia and Australia. RECENT FINDINGS: In Korea, allergy to Pachycondyla
      chinensis (subfamily Ponerinae) has been well described. In an ant-endemic area,
      sensitization was 23%, with about 1% having anaphylactic reactions. There were at
      least eight IgE-binding proteins in P. chinensis venom, with 1 major allergen
      binding 85% of patient sera. P. chinensis venom was also found to be possibly
      crossreactive with bee venom, but not with imported-fire-ant venom. In Australia,
      anaphylactic reactions to ant stings are usually caused by the 'jack jumper' ant
      (Myrmecia pilosula) or the bull ant (Myrmecia pyriformis). A recent study showed
      promising results for immunotherapy with M. pilosula venom. There have been
      reports of stings by other ant species in Asia and Australia, but these reports
      are few and sporadic. SUMMARY: The study of ant allergy in Asia is in its
      infancy. Clinicians in Asia need to be aware of ant stings as a cause of severe
      allergic reactions. Certain species that cause allergic reactions are unique to
      Asia and Australia and deserve further research. The allergens in the venom of
      the different ant species need to be identified. We should aim for improved
      understanding of the epidemiology of ant-sting anaphylaxis, formulation of better
      diagnostic tests and possibly the introduction of immunotherapeutic strategies.

PMID- 15238801
TI  - Bibliography. Current world literature. Drug allergy.

PMID- 15238804
TI  - Maintaining normality and support are central issues when receiving chemotherapy
      for ovarian cancer.
AB  - The aim of this study was to enrich the understanding of patients' perspective of
      being diagnosed and treated for ovarian cancer. A qualitative approach was used
      to obtain knowledge and insight into patients' experiences and thoughts. Ten
      Swedish women, diagnosed with ovarian cancer, participated in a total of 23
      interviews on 3 occasions: at the time of diagnosis, during chemotherapy, and
      after completion of chemotherapy. The results of the interpretation of the
      interviews were formulated in the form of 3 themes: (1) feeling the same despite
      radical castrating surgery, (2) accepting chemotherapy, and (3) maintaining
      normality and support. Suggestions of caring implications from our interpretation
      of the interview data underscore the need to support these women in learning to
      cope with their feelings of weakness and anxiety. The findings further indicate
      the potential in narrative methods to identify important issues in comprehensive
      cancer care.

PMID- 15238806
TI  - Colorectal cancer knowledge, perceptions, and behaviors in African Americans.
AB  - Disparities in healthcare among racial and ethnic minorities are associated with
      poor outcomes. African Americans have the highest incidence of colorectal cancer
      (CRC) among all racial groups. Using a nonrandom sample of 100 African American
      men and women, 50 years of age and older, the authors explored CRC knowledge,
      perceptions, and screening behaviors of African American men and women who
      resided or worked in an urban low-income housing residence. The extent to which
      screening may be attributed to demographic, sociopsychological, and structural
      variables was also investigated. Respondents demonstrated inadequate knowledge of
      CRC, with a significant difference in mean scores between males and females. Self
      report of participation in CRC screening was above the national average, with
      almost half of the sample reporting fecal occult blood home kit use and more than
      half of the sample reporting completion of sigmoid and colonoscopy exams and
      double contrast barium enema exam. A majority perceived CRC as a threat. A very
      high percentage perceived numerous benefits to CRC screening in preventing CRC
      susceptibility. Perceived barriers of nearly half of the sample included
      screening may be painful and afraid to find out something is wrong if I have CRC
      screening, while more than half did not know how to schedule screening. Barriers
      and threat were correlated with grade school education. Barriers were negatively
      correlated with secondary education and post-secondary education and moderately
      correlated with threat. Predictor variables found in the Health Belief Model
      accounted for a significant amount of the variance in screening behavior,
      barriers, and threat. Older African American men and women need more information
      about CRC in order to increase their awareness of CRC and the importance of
      screening. There is a need to educate healthcare professionals about the causes,
      prevention, and detection of CRC and the importance of screening.

PMID- 15238805
TI  - Prevention and treatment of oropharyngeal mucositis following cancer therapy: are
      there new approaches?
AB  - Oropharyngeal mucositis is an acute and distressing toxic effect of chemotherapy
      and head and neck irradiation. This oral sequela significantly impairs the daily
      functioning and quality of life of patients. The biological basis of mucositis is
      quite complex, involving sequential interaction of chemotherapeutic drugs or
      irradiation on mitosis of proliferating epithelium, a number of cytokines, and
      elements of oral microbial environment. Various interventions based on biological
      attenuation have been tested for mucositis. Such interventions have been reviewed
      elsewhere; however, most reviews focus on biomedical outcomes. Little attention
      has been paid to mucositis outcomes with oral morbidity or psychosocial aspects.
      The purpose of this article is to review the current research studies on the
      prevention and treatment of oropharyngeal mucositis following chemotherapy,
      radiotherapy, and bone marrow transplantation with an emphasis on biomedical,
      oral symptomatic, and functional impairment outcomes. In addition, further
      avenues of mucositis management, including psychotherapeutic intervention and
      integrated and stage-based treatment approaches are discussed.

PMID- 15238809
TI  - Micturition problems in relation to quality of life in men with prostate cancer
      or benign prostatic hyperplasia: comparison with men from the general population.
AB  - The aim of the study was to investigate men with prostate cancer and benign
      prostatic hyperplasia (BPH) in comparison with men from the general population in
      aspects of presence and frequency of micturition problems in remembrance of prior
      to treatment and currently. Further, the aim was to investigate the impact of
      micturition problems on quality of life and the association with micturition
      problems, and quality of life and sense of coherence (SOC). The samples consisted
      of 155 men with prostate cancer, 131 with BPH, and 129 from the general
      population. Micturition problems were assessed with study-specific questions,
      modified International Prostate Symptom Score (IPSS), quality of life
      questionnare (QLQ C-30), and SOC questionnaires. Parametric and nonparametric
      statistics were applied. Most troublesome urinary problems were leakage, feelings
      of discomfort, and disrupted urinary function and frequency. Men with urological
      diagnosis had more micturition problems, fatigue, and sleeping difficulties than
      men from the general population, but the cancer diagnosis did not add to the
      problems. Role and social functioning (prostate cancer), emotional functioning
      (BPH), and grade of fatigue (general population) showed itself vital for overall
      quality of life. Thus, help in solving issues of micturition problems, fatigue,
      and sleeping disturbances may contribute to maintenance of role, social, and
      emotional aspects of life.

PMID- 15238811
TI  - Social support and coping in Chinese patients undergoing cancer surgery.
AB  - Patients undergoing cancer surgery experience the threats from both cancer and
      surgery. The unique sociocultural characteristics of Hong Kong Chinese may affect
      their perception of social support and how they face these threatening
      experiences. Sixty eligible patients were recruited from 2 regional hospitals in
      Hong Kong. They were asked to respond to a set of questionnaires, including
      Norbeck Social Support Questionnaire (NSSQ), Informational Support Questionnaire,
      and Jalowiec Coping Scale, following cancer surgery. The results showed that
      although family members and spouse/partner represented the largest source of
      social support network, the overall quantity of social support received by
      Chinese patients after cancer surgery was low. Positive correlations were found
      between coping effectiveness with tangible support (r = 0.31, P <.05) and coping
      effectiveness with informational support (r = 0.52, P <.01). The findings of this
      study support the link between social support and successful coping following
      cancer surgery. Tangible and informational supports appear more relevant to
      effective coping than emotional support during the postoperative period.
      Inclusion of family members in patient care during the postoperative period is
      crucial. Special attention should be paid to those patients who are older and
      poorly educated as they may be highly at risk for inadequate social support.
      Further studies with other cultural groups are suggested in order to better
      understand the sociocultural factors associated with cancer care.

PMID- 15238812
TI  - Meanings of the phenomenon of fatigue as narrated by 4 patients with cancer in
      palliative care.
AB  - The disabling experience of fatigue suffered in connection with incurable cancer
      is an area within nursing that has generated only limited research interest. The
      need for a change in focus is presented in the literature: from treating the
      symptom itself to facilitating living with the fatigue caused by a life
      threatening disease. This implies that helping to alleviate fatigue must start
      from the patients' own understanding and interpretation of this experience. Our
      study attempts to achieve this understanding through illuminating the meanings of
      fatigue as experienced by 4 patients with cancer in palliative care. The research
      interviews were analyzed using a phenomenological-hermeneutic approach inspired
      by the philosophy of Ricoeur. Our findings indicate a world in which one meaning
      of fatigue connected with incurable cancer is a lived bodily experience of
      approaching death. Comprehending fatigue in this way allows us to understand the
      paradoxes we found in the text, such as struggling in vain against fatigue, and
      hoping to overcome fatigue but expecting failure. The paradoxes represent a
      struggle between body and mind, between bodily experiences and intellectual
      understanding, and have important implications for how we communicate with
      patients about fatigue.

PMID- 15238813
TI  - Health problems encountered by dying patients receiving palliative home care
      until death.
AB  - Many of the studies reviewing the needs of the dying patient have used specified
      time points rather than following the patients through the last span of their
      lifetime, until death. This prospective study, using clinical records and nursing
      anecdotes, examined the health problems encountered by dying patients receiving
      home care from referral to home care until death. Thirty-two subjects were
      recruited in the study. The clinical records were content-analyzed using the
      Omaha system, and the anecdotes of the nurses were used to illuminate the
      numerical findings. This study reveals that patients who were discharged home
      were living in good environmental and social conditions. The physical symptoms
      were generally well controlled, except for dyspnea. The psychological aspects
      caused the most concern to patients, families, and healthcare professionals. The
      severity of the psychological signs and symptoms was moderate at the time of the
      initial visits, but improved toward the final visits. Understanding the needs of
      palliative home care patients can facilitate the healthcare team to plan care to
      support "good dying" of these patients.

PMID- 15238816
TI  - Emphasis on pleiotropic effects, a new paradigm shift?

PMID- 15238814
TI  - Reliability and validity of the Turkish version of Multidimensional Quality of
      Life Scale--Cancer Version 2 in patients with cancer.
AB  - This study examined the reliability and validity of the Turkish version of the
      Multidimensional Quality of Life Scale - Cancer Version 2 (MQOLS-CA2) in 72
      people with cancer. The results indicated that the MQOLS-CA2 has good construct
      validity. Factor analysis confirmed the presence of 5 factors in the MQOLS-CA2:
      psychological well-being, physical well-being, nutrition, symptom distress, and
      interpersonal well-being. The correlation between the global scores of the MQOLS
      CA2 and Medical Outcomes Study 36-Item Short Form Health Survey was significant
      (r = 0.78, P =.0001), supporting the criterion validity of the MQOLS-CA2. Results
      of the test-retest method showed that stability coefficients for the 5 subscales
      of the MQOLS-CA2 ranged from 0.56 (symptom distress) to 0.91 (general physical
      well-being). Cronbach alpha coefficients surpassed the 0.70 criterion for all
      subscales, indicating good internal consistency. The acceptability rate was
      excellent at 96% completed questionnaires. In conclusion, the findings suggest
      that the Turkish version of the MQOLS-CA2 is a valid and reliable instrument that
      can be used in cancer research.

PMID- 15238817
TI  - Effects of statin therapy on vascular dysfunction.
AB  - Dyslipidemia and vascular inflammation play critical roles in the onset of acute
      coronary syndromes including myocardial infarction. Recent advances in
      cardiovascular medicine demonstrate that lipid-lowering therapy by 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) prevents acute
      coronary complications, probably by limiting inflammation in atheroma. Although a
      number of studies have suggested various effects of statins on vascular
      dysfunction independent of lipid lowering, the clinical benefits of such effects
      are not established as yet.

PMID- 15238818
TI  - Effects of statins on endothelium and their contribution to neovascularization by
      mobilization of endothelial progenitor cells.
AB  - Statins are potent drugs with a variety of cardiovascular protective effects
      which appear to occur independent of cholesterol reduction. The vasculoprotective
      effects of statins might be due to their direct effect on endothelial cells
      leading to improved nitric oxide (NO) bioavailability. Mechanistically, statins
      induce endothelial nitric oxide synthesis (eNOS) mRNA stability in endothelial
      cells and promote eNOS activity through a PI3K/Akt dependent pathway. Novel
      targets of statins are pro-angiogenic actions including the mobilization and
      differentiation of bone marrow derived endothelial progenitor cells, which
      accelerate angiogenesis or re-endothelialization. The functional improvement and
      increased homing capacity of endothelial progenitor cells induced by statin
      treatment might reverse impaired functional regeneration capacities seen in
      patients with risk factors for coronary artery disease or documented active
      coronary artery disease.

PMID- 15238819
TI  - The cardioprotective effects of statins.
AB  - Many large randomized clinical trials have demonstrated that statins are
      effective in terms of prevention of cardiovascular events. It has been presumed
      that these beneficial effects could be due to not only improved plasma lipid
      profiles but also to the direct actions on the vascular wall. In addition to the
      direct vascular protective effects, several lines of experimental evidence have
      been accumulated that statins have also cardioprotective effects against
      ischaemia/reperfusion injury. This effect appears to be a class-effect and
      activation and up-regulation of eNOS by statins play an important role.

PMID- 15238821
TI  - The antioxidant effects of statins.
AB  - Oxidative stress contributes to the initiation and the development of
      atherosclerotic plaques and adversely influences myocardial integrity. Statins
      interfere with oxidation in several ways that may contribute to reducing the
      atherogenic process. In addition to direct antioxidant effects, statins reduce
      circulating oxidized low-density lipoproteins (oxLDL) and inhibit their uptake by
      macrophages. They also reduce circulating markers of oxidation such as F2
      isoprostane and nitrotyrosine. Statins inhibit oxidant enzymes activity such as
      that of reduced nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase and
      myeloperoxidase and up-regulate the activity of antioxidant enzymes such as
      catalase and paraoxonase. They reduce endothelial dysfunction mainly by their
      ability to enhance endothelial nitric oxide bioavailability, which is achieved by
      several mechanisms. The antioxidant properties of statins extend to organ
      protection especially the myocardium and the lungs.

PMID- 15238820
TI  - Statins and myocardial hypertrophy.
AB  - Cardiac hypertrophy is a physiological adaptive response by the heart to pressure
      overload. However, after prolonged periods, this initial adaptive response
      becomes maladaptive, leading to increased mortality and morbidity from heart
      failure. Recently, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, or statins, have been shown to inhibit cardiac hypertrophy by
      cholesterol-independent mechanisms. Statins block the isoprenylation and
      activation of members of the Rho guanosine triphosphatase (GTPase) family, such
      as RhoA and Rac1. Since Rac1 is a requisite component of reduced nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase, which is a major source of
      reactive oxygen species (ROS) in cardiovascular cells, the ability of statins to
      inhibit Rac1-mediated oxidative stress makes an important contribution to their
      inhibitory effects on cardiac hypertrophy.

PMID- 15238822
TI  - Microvascular dysfunction in angiographically normal or mildly diseased coronary
      arteries predicts adverse cardiovascular long-term outcome.
AB  - OBJECTIVE: To study the role of coronary flow reserve for the prediction of long
      term cardiovascular event rate. DESIGN: Observational, longitudinal. SETTING:
      Single-center, coronary vasomotor testing at university hospital. PARTICIPANTS:
      One hundred and twenty patients with angiographically normal or minimally
      diseased coronary vessel. METHODS: Coronary flow reserve was assessed by
      intracoronary Doppler and quantitative coronary angiography. Cardiovascular
      events during follow-up (6.5+/-3 years, range 14-125 months) were defined as
      sudden death, myocardial infarction, unstable angina, ischemic stroke or the need
      for revascularization by percutaneous transluminal coronary angioplasty or
      coronary as well as peripheral bypass surgery. RESULTS: Reduced coronary flow
      reserve was significantly associated with a poor long-term outcome:
      cardiovascular events occurred in seven (18%) patients in the lowest tertile of
      coronary flow reserve compared with four patients in the middle tertile (10%) and
      two patients in the upper tertile (5%) (P=0.019 by Kaplan-Meier analysis). The
      multivariate Cox proportional hazard model revealed coronary flow reserve as an
      independent predictor of prognosis (P=0.017) in addition to angiographic evidence
      of atherosclerosis (P=0.047) and arterial hypertension (P=0.013). CONCLUSIONS:
      Coronary flow reserve in normal to mildly diseased arteries is an independent
      predictor of long-term prognosis of atherosclerosis within the next decade.

PMID- 15238823
TI  - Activation of coagulation system in dilated cardiomyopathy: comparison of
      patients with and without left ventricular thrombus.
AB  - OBJECTIVES: We aimed to investigate plasma levels of molecular markers for
      platelet activity, thrombin activation and fibrinolytic status in patients with
      dilated cardiomyopathy (DCM) with and without left ventricular (LV) thrombus and
      to compare these markers between patients with DCM and control participants.
      MATERIALS AND METHODS: The study population comprised 60 patients with DCM who
      met the inclusion criteria. Patients were divided into two groups: 22 patients
      with LV thrombus and 38 patients without LV thrombus. The age-matched control
      group consisted of 23 healthy participants (18 men and five women with a mean age
      of 49). Patients with DCM and healthy participants were compared with respect to
      platelet activity, thrombin activation and fibrinolytic status. These comparisons
      were also performed in patients with DCM with and without LV thrombus. RESULTS:
      Platelet factor 4 (28.2+/-4.4 ng/ml compared with 20+/-3.1 ng/ml, P<0.01) and
      beta-thromboglobulin (40+/-2 ng/ml compared with 17+/-3 ng/ml) levels, reflecting
      platelet activity, were significantly higher in patients with DCM than in control
      participants. Fibrinopeptide A (6.94+/-0.69 ng/ml compared with 1.96+/-0.1 ng/ml,
      P<0.001) and thrombin-antithrombin III complex (5.26+/-2.60 ng/ml compared with
      3.17+/-1.23 ng/ml, P<0.001) levels, as markers of fibrin generation, were also
      higher in patients with DCM than in normal participants. Plasma levels of D-dimer
      (118+/-16 ng/ml compared with 85+/-3 ng/ml, P<0.001) and plasmin-alpha2-plasmin
      inhibitor complex (0.8+/-1.1 microg/ml compared with 0.6+/-1.7 microg/ml,
      P<0.001) in patients with DCM significantly exceeded those in the normal
      participants. There were no statistically significant differences between
      patients with and without LV thrombus in DCM with respect to platelet activity,
      thrombin activation and fibrinolytic status. CONCLUSION: We have shown that
      platelet activation, thrombin activation and fibrinolytic activity are increased
      in patients with DCM compared to control participants. However, these markers
      reflecting coagulation activation in patients with LV thrombus are comparable to
      those in patients without LV thrombus.

PMID- 15238824
TI  - Does resting two-dimensional echocardiography identify patients with ischemic
      cardiomyopathy and low likelihood of functional recovery after coronary
      revascularization?
AB  - OBJECTIVE: To evaluate the potential of a simple and widely available technique
      as two-dimensional (2D) echocardiography to identify patients with ischemic
      cardiomyopathy and low likelihood of functional recovery after coronary
      revascularization. METHODS: Two-dimensional echocardiography and radionuclide
      ventriculography (RNV) were performed before coronary revascularization in 94
      patients with ischemic cardiomyopathy. Left ventricular ejection fraction (LVEF)
      was measured by RNV. Regional wall motion abnormalities, wall motion score index,
      end-diastolic wall thickness (EDWT), left ventricular (LV) volumes and LV
      sphericity index were assessed in the echocardiographic images. RNV was repeated
      9-12 months after revascularization to assess LVEF change; an improvement >or=5%
      was considered clinically significant. RESULTS: Nine hundred and ninety-nine
      segments were severely dysfunctional; 149 out of 999 (15%) had an EDWT <or=6 mm.
      A severe enlargement of the end-diastolic volume index (EDVI) (>or=100 ml/ml) and
      of the end-systolic volume index (>or=80 ml) was present in 32 (34%) and 21 (22%)
      patients, respectively. A spherical shape of the LV was observed in 35 (37%)
      patients. LVEF after revascularization increased in 30 out of 94 patients (32%)
      from 30+/-8% to 39+/-9% (P<0.0001). On multivariate analysis, the EDVI was the
      only predictor of no recovery in LVEF [odds ratio, 1.06, confidence interval
      (CI), 1.04-1.1, P<0.0001]. The cut-off value of EDVI >or=90 ml/ml accurately
      identified patients that virtually never recover. Post-operatively, LVEF
      increased in three out of 42 (7%, 95% CI 0-15%) patients with EDVI >or=90 ml/ml
      as compared to 27 out of 52 (52%) patients with EDVI<90 ml/ml (P<0.0001).
      CONCLUSIONS: In patients with ischemic cardiomyopathy and severe LV enlargement,
      improvement of LVEF after revascularization is unlikely to occur. Conversely, in
      patients with relatively preserved LV size, a higher likelihood of functional
      recovery may be anticipated.

PMID- 15238825
TI  - The effects of lipid-lowering therapy on paraoxonase activities and their
      relationships with the oxidant-antioxidant system in patients with dyslipidemia.
AB  - BACKGROUND: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, which is used for lipid-lowering therapy, is an effective statin
      modulating process involved in atherosclerosis. Paraoxonase (PON) associated with
      high-density lipoprotein (HDL) has been postulated to have a role in protecting
      low-density lipoprotein (LDL) against oxidative modification. Oxidation of serum
      LDL is an important early step in the development of atherosclerosis and auto
      antibodies against oxidized LDL (AuAb-oxLDL) reflect in-vivo LDL oxidation.
      DESIGN AND METHODS: To examine the effect of atorvastatin (10 mg/day) therapy on
      PON activity in serum and HDL, the study group included 40 patients with
      dyslipidemia (19 women and 21 men), 25 of whom had hypercholesterolemia and of 15
      of whom had mixed-type hyperlipidemia. By taking blood samples from the patients,
      levels of serum lipids, lipid peroxidation product as malondialdehyde (MDA),
      total antioxidant status (TAS) and AuAb-oxLDL and the activities of PON in serum
      and isolated HDL were determined. RESULTS: The mean levels of total cholesterol,
      triglyceride, LDL-cholesterol, MDA and AuAb-oxLDL were decreased while HDL
      cholesterol and TAS were increased significantly after lipid-lowering therapy in
      patients with dyslipidemia. On the other hand, PON activities in serum and HDL
      were increased significantly. The percentage increase in serum PON activity was
      associated significantly with the percentage decrease in serum AuAb-oxLDL (r=
      0.32, P=0.047) and that of HDL PON activity was associated with the percentage
      increase in HDL-cholesterol level after atorvastatin therapy (r=0.52, P=0.001).
      The therapy was more effective in increasing PON activity in patients with HDL
      levels above 35 mg/dl. CONCLUSION: It was concluded that atorvastatin therapy in
      dyslipidemic patients decreases the level of oxidative stress and increases PON
      activity, especially in patients with HDL levels above 35mg/dl.

PMID- 15238826
TI  - Intracoronary brachytherapy with beta-radiation for the treatment of long diffuse
      in-stent restenosis.
AB  - OBJECTIVE: To assess the efficacy of intracoronary brachytherapy with beta
      radiation (Sr/Y) for the treatment of long diffuse in-stent restenosis (ISR).
      METHODS: As recurrent ISR depends on intimal injury after coronary angioplasty,
      long in-stent restenotic lesions were defined as lesions with a treatment length
      >26 mm (lesion length >20 mm plus a treatment margin of 3 mm at each end).
      Seventy-eight patients with long ISR were treated at our institution with beta
      brachytherapy after coronary angioplasty. Patients were irradiated with either an
      approximate dose of 12 Gy at 1 mm vessel wall depth or with 18 Gy at 1 mm vessel
      wall depth. Clinical follow-up was available for 69 patients and angiographic
      follow-up for 65 patients. Late lumen loss (LLL), binary restenosis (stenosis
      >50%), target lesion revascularization (TLR) and major adverse cardiac events
      (MACE) were assessed for a follow-up time of 6.6+/-2.2 months. RESULTS: Mean
      interventional treatment length was 46+/-18 mm. TLR was performed in all 23
      patients with binary restenosis (33%). Death of cardiac cause was reported for
      two patients, one of whom did not undergo TLR. Thus, overall MACE rate was 35%.
      Recurrent ISR was significantly more frequent in patients with geographic miss.
      Comparison of the different radiation dose regimens revealed significantly lower
      LLL in patients irradiated with the higher dose (0.20+/-0.68 mm compared with
      0.65+/-0.96 mm, P=0.03). CONCLUSION: Intracoronary brachytherapy with beta
      radiation (Sr/Y) is a safe and effective therapeutic option for the reduction of
      recurrent ISR in long diffuse lesions. We recommend a high-dose irradiation with
      18 Gy at 1 mm vessel wall depth.

PMID- 15238828
TI  - Bibliography current world literature.

PMID- 15238827
TI  - Progression of coronary artery disease in non-ischemic dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is traditionally divided into ischemic and non
      ischemic etiologies. We review data from clinical trials that suggest some
      patients in the latter subgroup develop ischemic complications including fatal
      myocardial infarction. However, the reasons for and magnitude of the effect are
      not known. Prospective screening studies and improved endpoint adjudication in
      clinical trials may be required to better delineate the degree to which the
      phenomenon occurs. Risk factor modification strategies should be applied to the
      non-ischemic DCM cohort, especially with continued improvements in survival rates
      in patients with heart failure.

PMID- 15238852
TI  - Prevent cardiovascular disease in women.

PMID- 15238853
TI  - Insight into a court's analysis.

PMID- 15238854
TI  - The APN's guide to pediatric constipation management.

PMID- 15238856
TI  - Early identification key to scleroderma treatment.

PMID- 15238858
TI  - Celiac sprue treatment in primary care.

PMID- 15238859
TI  - CHF in the elderly using ACEIs appropriately.

PMID- 15238860
TI  - Vaginal ring an HT alternative.

PMID- 15238861
TI  - Inspra improves survival for CHF patients.

PMID- 15238868
TI  - [Ultrasound imaging of focal liver lesions with contrast agents: which clinical
      applications?].
AB  - The contrast-enhanced ultrasonography is a promising technique for the diagnosis
      of focal liver lesion with an increased sensitivity for the tumour detection and
      a direct visualization of the tumour vascularity. The future applications of this
      technique will probably depend on the clinical context: in case of suspicion of
      benign tumour, contrast injection should be able to facilitate the
      characterization of hemangiomas and focal nodular hyperplasia, when hepatic
      metastases are researched, it may improve the detection of small lesions in
      cirrhotic patients, it may facilitate the detection of small hepatocellular
      carcinomas and find a place in the systematic screening for these tumours. The
      recently published data are encouraging, but a confirmation of the clinical
      interest of this technique, and its place within the imaging diagnostic
      strategies still have to be performed.

PMID- 15238869
TI  - [Contrast ultrasound imaging in focal liver lesions: diagnostic value and
      guidelines].
AB  - The recent introduction of high quality scanners and contrast agents for
      ultrasound deeply modifies diagnosis strategy in focal liver lesions by using
      validated criteria. Non-linear imaging methods using low mechanical index
      (MI<0.2) and second generation contrast agents allow real-time continuous imaging
      with concomitant limitation in background tIssue signal and also in agent
      collapse for a high quality contrast imaging giving dramatic improvement in
      detection and characterization of lesions. Interpretation is based on the
      presence of contrast agent within the lesion or not (hyper-, hypo- or isosignal)
      and the delay after injection (arterial, portal or parenchymal or late phase) as
      previously used by non-ultrasound methods. This allows an easy differentiation of
      benign from malignant lesions. Moreover, this allows complete characterization in
      85 to 95% of all focal liver lesions and 75% in hepatocellular carcinomas. Those
      results markedly improve ultrasound accuracy compared to conventional sonography
      and so put contrast-enhanced sonography among recommended non-invasive imaging
      methods for focal liver lesions with changes in diagnostic strategy according to
      the lesion type and actual place of US methods. It is recommended to use contrast
      ultrasound methods in cancer staging for an optimal detection of liver metastases
      as well as in characterization of lesions detected during conventional sonography
      with a consecutive decrease of cost-diagnosis ratio.

PMID- 15238870
TI  - [The role of contrast-enhanced ultrasonography for the detection of
      hepatocellular carcinoma].
AB  - The incidence of the hepatocellular carcinoma (HCC) is increasing in Occident, as
      well as in France. Primary prevention is the only solution for early detection.
      The combination of ultrasound (US) and alphaFP each 4 to 6 Months dosage has many
      limitations. The sensitivity of US examination is rather poor (less than 70% for
      lesions below 2 cm in diameter) and serum alphaFP values remain normal in almost
      50% of HCC. US contrast agents (USCAs) with perfluorocarbon gases increase the
      backscattered signals during all phases of the liver transit, including arterial,
      portal and delayed phases. Hepatocellular lesions exhibit a specific kinetics
      with strong enhancement during arterial phase, and rapid wash-out during portal
      and delayed phases. USCAs increase the detection of HCCs and allow
      characterization of additional focal lesions found in cirrhotic livers
      (regenerative and dysplastic nodules, haemangiomas.). Indeed, regenerative
      nodules contrast uptake is synchronous to the surrounding parenchyma, and usually
      disappear during portal and delayed phases. However, US in cirrhosis remains a
      difficult examination, with limitations due to limited access to sub
      diaphragmatic localization, attenuation of the ultrasound beam and shortness of
      the arterial phase.

PMID- 15238871
TI  - [Functional and early evaluation of treatments in oncology: interest of
      ultrasonographic contrast agents].
AB  - The early and functional evaluation of new treatments in oncology is a main goal.
      At present, technical advances in Doppler-ultrasonography allow the detection of
      neovascularization for superficial and deep malignant tumors in order to evaluate
      the efficiency of new treatments as Treatment response can be early predicted
      according to modifications of this vascularization before Volume modification.
      Contrast agents injection improves the efficiency of this technique and
      developments in perfusion softwares optimize this detection.

PMID- 15238872
TI  - The K65R mutation in HIV-1 reverse transcriptase.

PMID- 15238873
TI  - Essential benefits of nucleoside analogue regimens in failing therapy.
AB  - Since the introduction of highly active antiretroviral therapy, nucleoside and
      more recently nucleotide reverse transcriptase inhibitors (NRTIs) have provided a
      highly effective backbone to antiretroviral regimens based on non-nucleoside
      reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).
      Nonetheless, treatment failure can result from poor adherence, unfavourable
      pharmacokinetics, advanced disease or infection with a drug-resistant virus.
      Recent data have also indicated a high risk of virological failure with triple
      NRTI regimens, reflecting overall lower potency compared to combinations of NRTIs
      with either NNRTIs or PIs. Resistance mutations emerging upon failure can cause
      extensive cross-resistance among available NRTIs, and potentially affect
      susceptibility to newly developed antiretroviral drugs. However, despite the
      emergence of resistance, NRTIs can retain significant antiviral activity in
      treatment-experienced patients. This may reflect residual direct viral load
      suppression, as well as indirect effects related to impaired viral fitness of
      NRTI-resistant mutants and antagonist interactions between resistance mutations.

PMID- 15238874
TI  - The role of nucleoside reverse transcriptase inhibitors in the fat redistribution
      syndrome.
AB  - Fat redistribution associated with the use of antiretroviral therapy, which has
      been broadly termed 'lipodystrophy', incorporates distinct body composition
      changes including lipoatrophy (subcutaneous fat loss) as well as fat
      accumulation. This review examines the role of nucleoside reverse transcriptase
      inhibitor (NRTI) therapy in the overall context of lipodystrophy, providing
      converging evidence from observational cohort studies, clinical trials and
      pathological studies that lipoatrophy is strongly and specifically associated
      with the use of certain NRTI drugs (stavudine more than zidovudine), and that
      host factors also have a modulating effect on risk of NRTI-associated
      lipoatrophy. Implications for clinical assessment and management are also
      considered, within a broader contest that incorporates treatment efficacy as well
      as toxicity.

PMID- 15238875
TI  - Does atazanavir cause lipodystrophy?
AB  - Atazanavir is a once-a-day non-pepsidic inhibitor of HIV protease which is
      licensed for use in the UK and the USA. One of its major advantages is that it
      does not produce lipid abnormalities in patients who receive it. This feature has
      been widely interpreted as implying that in the future there will be no
      abnormalities associated with fat redistribution when the drug is administered.
      This article explores that view.

PMID- 15238876
TI  - Mitochondrial toxicity: myths and facts.
AB  - Nucleoside analogue reverse transcriptase inhibitors (NRTIs) represent key
      components of the antiretroviral combinations used to manage HIV infection. A
      range of nucleoside analogues are currently available which differ in their
      convenience of administration, frequency of dosing, resistance profile and
      frequency and severity of adverse effects. Many of the important and treatment
      limiting side-effects of nucleoside analogues have been suggested to be related
      to the impact of these agents on mitochondrial DNA polymerase gamma. Depletion of
      mitochondrial DNA or impacts of these agents on mitochondrial enzymes during
      chronic nucleoside analogue therapy may lead to cellular respiratory dysfunction
      and both generalised and tissue specific toxicities. In particular, fatal lactic
      acidosis represents a rare but clinically important manifestation of nucleoside
      analogue induced mitochondrial dysfunction. Other potentially severe toxicities
      which are well-characterised include peripheral neuropathy (PN) and myopathy.
      Management of potentially mitochondrial toxicity during nucleoside analogue
      therapy remains a challenge. A range of nutritional supplements, both as
      treatments and prophylaxes have been proposed and some investigated in vitro but
      not as yet in vivo. At present, therefore, interruption of nucleoside analogue
      therapy, or substitution of the probable causative agent with nucleoside
      analogues which appear better tolerated represent the mainstay of management.

PMID- 15238877
TI  - Circulating stem cells and tissue repair.
AB  - Stem cells are defined as cells that have clonogenic, self-renewing capacities
      and the capability to differentiate into multiple cell lineages. Whereas
      embryonic stem cells are derived from mammalian embryos in the blastocyst stage
      and can generate terminally differentiated cells of all 3 embryonic germ layers,
      adult human stem cells are capable of maintaining, generating, and replacing
      terminally differentiated cells within their own specific tissue as a consequence
      of physiologic cell turnover or tissue injury. The traditional idea of organ
      restricted stem-cell differentiation is now being challenged by the suggestion
      that adult stem cells retain developmental plasticity. Preclinical and clinical
      studies described in this review provide evidence that within the blood circulate
      not only progenitor cells that differentiate into hematopoietic cells, but also
      stem/progenitor cells which can participate in the homeostasis, repair and
      replacement of solid organ tissues. In addition to the occurrence of cell fusion,
      there are 4 suggested mechanisms of adult stem cell differentiation into solid
      organ cells. Preclinical data support these models particularly that of
      transdifferentiation as the most likely model, allowing stem/progenitor cells to
      differentiate across lineage, tissue, and germ layer boundaries. There is
      increasing evidence that we can manipulate in vivo circulating adult stem cells
      to repair or regenerate solid organ tissue, which offers potential clinical
      benefit in the treatment of many hereditary and acquired diseases.

PMID- 15238878
TI  - Cell therapy for ischemic heart disease.
AB  - Despite advances in pharmacological therapies, cardiovascular surgery, use of
      mechanical assist devices, and organ transplantation, more than 50% of the
      patients with clinically evident heart failure die within 5 years of the initial
      diagnosis. The use of cellular therapy offers a promising approach for both the
      prevention and treatment of heart failure. This review will discuss the current
      state of this emerging field and the prospects to introduce the method into
      clinical practice. Since functional restoration of the damaged heart presents a
      formidable challenge, developing strategies for the prevention of postinfarct
      heart failure remains of utmost priority. Recent research has provided evidence
      that several cell lines including adult or embryonic stem cells, skeletal
      myoblasts, fetal cardiomyocytes or fibroblasts may be useful in strategies that
      aim to both prevent and treat heart failure through establishment of new blood
      vessels supplying surviving heart muscle cells and replacement of damaged heart
      muscle cells themselves. It is therefore reasonable to anticipate that new
      strategies will be developed to optimize cell delivery, homing and survival in
      the failing myocardium improving myocardial recovery after acute or chronic
      deterioration.

PMID- 15238880
TI  - Prospects for cell-based therapies for liver disease.
AB  - Liver parenchymal maintenance and regeneration after injury are physiologically
      supported by 3 cell compartments: mature liver cells, intra-organ stem cells such
      as cells of the proximal biliary tree and periductal cells, and extra-organ stem
      cells from the circulation and the bone marrow. In the latter case, hepatocyte
      derivation from circulating cells (plasticity) can arise via direct
      transdifferentiation (site specific, receptor/ligand dependent) or by fusion of
      circulating cells with pre-existing hepatocytes. Other non-physiologic stem
      cells, such as mesenchymal stem cells from the bone marrow and embryonic stem
      cells, may be potentially used in treatment of inherited and acquired liver
      diseases. This review updates our current understanding of these various cell
      populations and of possible approaches to their future therapeutic uses in cell
      transplantation, bioartificial liver devices, cytokine/chemokines manipulation of
      physiological repair pathways, and gene therapy.

PMID- 15238879
TI  - Pancreatic islet and stem cell transplantation: new strategies in cell therapy of
      diabetes mellitus.
AB  - Long-term studies strongly suggest that tight control of blood glucose can
      prevent the development and retard the progression of chronic complications of
      type 1 diabetes mellitus. In contrast to conventional insulin treatment,
      replacement of a patient's islets of Langerhans either by pancreas organ
      transplantation of by isolated islet transplantation is the only treatment to
      achieve a constant normoglycemic state and avoiding hypoglycemic episodes, a
      typical adverse event of multiple daily insulin injections. However, the expense
      of this benefit is still the need for immunosuppressive treatment of the
      recipient with all its potential risks. Islet cell transplantation offers the
      advantage of being performed as a minimally invasive procedure, in which islets
      can be perfused percutaneously into the liver via the portal vein. As of June
      2003, 705 pancreatic islet transplants worldwide have been reported to the
      International Islet Transplant Registry (ITR) at our Third Medical Department,
      University of Giessen/Germany. Data analysis shows at 1 year after adult islet
      transplantation a patient survival rate of 97%, a functioning islet graft in 54%
      of the cases, whereas insulin independence was meanwhile achieved in 20% of the
      cases. However, using a novel protocol established by the Edmonton Center/Canada,
      the insulin independence rates have improved significantly reaching meanwhile a
      50-80% level. Finally, the concept of islet cell or stem cell transplantation is
      most attractive since it offers many perspectives: islet cell availability could
      become unlimited and islet or stem cells my be transplanted without life-long
      immunosuppressive treatment of the recipient, just to mention 2 of them.

PMID- 15238881
TI  - Stem cells in gynecology and obstetrics.
AB  - Over the past 10 years, we have become involved in a new research effort and an
      increasing scientific interest in the field of stem cell-based therapy. We are
      therefore able to describe different areas in which stem cell research can be
      applied and developed in gynecology and obstetrics. I) Hematopoietic stem cells
      have been used to set up therapeutic strategies for the treatment of
      gynecological solid tumors such as ovarian cancer. In this context different
      autologous or allogeneic transplantation approaches have been proposed and
      clinically investigated. II) Umbilical cord blood, which was often considered a
      waste material of the delivery, actually represents a precious source of stem
      cells that can be used for cell-based treatments of malignancies and inherited
      diseases. III) A feto-maternal cell traffic has recently been demonstrated
      through the placental barrier during pregnancy. This cellular exchange also
      includes stem cells from the fetus, which can generate microchimerisms in the
      mother and contribute to tissue repair mechanisms in different maternal organs.
      IV) Stem cells can be used for prenatal transplantation to treat different severe
      congenital diseases of the fetus. Nevertheless, several problems need to be
      solved to achieve an efficient in utero stem cell transplantation. Recent reports
      have pointed out the importance of timing in prenatal stem cell transplantation
      procedures and have shown the advantage of an early stem cell injection. An
      ultrasound-guided intracelomic approach could allow this possibility.

PMID- 15238882
TI  - Hematopoietic stem cell transplantation in hematologic malignancy.
AB  - Hematopoietic stem cell transplantation has become increasingly important in the
      treatment of hematologic malignancies over the past 20 years. While it is
      associated with significant morbidity, it offers the only chance of cure in many
      circumstances. Autologous and allogeneic transplantation have been used
      successfully to treat a variety of hematologic malignancies. These 2 approaches
      offer different risks and benefits which are discussed in this review. Timing of
      transplantation and selection of patients are also discussed. New innovations in
      stem cell transplantation including umbilical cord blood and non-myeloablative
      transplantation are reviewed.

PMID- 15238883
TI  - Stem cell therapy for neurological disease and injury.
AB  - Despite the anatomical protection provided to the central nervous system (CNS) by
      the skull and vertebral column, it is still vulnerable to a variety of injuries
      as well as a number of neurodegenerative diseases. There is little endogenous
      repair of the CNS, so functional recovery from injury is typically modest. Most
      neurodegenerative diseases are progressive in their course and few effective
      therapies exist to delay this disease progression or to promote any recovery.
      With the understanding that the adult brain can support the generation of new
      neurons in certain locations and with advances in understanding the biology of
      such stem or progenitor cells, there is now considerable hope that neural or non
      neural derived stem cells can be used for structural brain repair. This review
      provides an overview of our current understanding of the biology of neural stem
      cells and their ability to integrate into the mature CNS. The prospects for using
      grafted stem cells or recruiting endogenous stem cells to treat neurological
      injury or disease are evaluated.

PMID- 15238884
TI  - Myogenic cellular transplantation and regeneration: sorting through progenitor
      heterogeneity.
AB  - Growth and regeneration of skeletal muscle fibers in response to injury are made
      possible by the presence of resident myogenic progenitor cells. Researchers have
      attempted to isolate and transplant these cells to regenerate new muscle in cases
      involving injury, disease, or genetic deficiencies. Reports from such experiments
      underscore the functional diversity of progenitors obtained from skeletal muscle;
      however, currently there is no reliable means by which to positively identify and
      isolate the most desirable muscle progenitor populations. Taking a cue from the
      hematopoietic community, researchers in this area have begun to investigate cell
      surface protein expression in progenitor populations. Previous findings in
      cultured myogenic cells and our results in cells obtained directly from
      dissociated muscle suspensions indicate that cells sorted based on their
      expression of the commonly-studied myogenic cell surface proteins Sca-1 and CD34
      exhibit differing regenerative abilities. However, results obtained to date are
      insufficient to clearly delineate whether the expression of either of these
      proteins is an exclusive characteristic of efficient myogenic progenitors.
      Nonetheless, observations from these studies clearly suggest that progenitor
      heterogeneity should be an important consideration during the development and
      implementation of muscle regeneration strategies. Additional research is
      necessary to establish reliable selection criteria for the isolation of efficient
      progenitors, which will facilitate therapeutic discoveries and enhance our
      understanding of factors affecting regeneration outcomes.

PMID- 15238885
TI  - Epidemiology of pancreatic cancer.
AB  - Worldwide, over 200000 people die annually of pancreatic cancer. The highest
      incidence and mortality rates of pancreatic cancer are found in developed
      countries. In the United States, pancreatic cancer is the 4(th) leading cause of
      cancer death, and in Europe it is the 6th. Because of high fatality rates,
      pancreatic cancer incidence rates are almost equal to mortality rates. Pancreatic
      cancer is diagnosed late in the natural history of the disease, given the few
      early indicators of illness, and the lack of screening tests for this disease.
      Treatment has not improved substantially over the past few decades and has little
      effect on prolonging survival time. Therefore, prevention could play an important
      role in reducing pancreatic cancer mortality. International variations in rates
      and time trends suggest that environmental factors are likely to play a role in
      the etiology of pancreatic cancer. Variations in rates are substantial and occur
      even within industrialized nations. While rates have been stabilizing over the
      past 2 decades in many countries where they are already high, they continue to
      increase in countries where rates were relatively low 4 decades ago, such as
      Japan. In the US, the highest rates of pancreatic cancer incidence and mortality
      are observed among blacks, who have some of the highest rates in the world. A
      known cause of pancreatic cancer is tobacco smoking. This risk factor is likely
      to explain some of the international variations and gender differences. A number
      of studies observed a reduction in pancreatic cancer risk within a decade after
      smoking cessation, when compared to current smokers. With tobacco smoking as an
      exception, risk factors for pancreatic cancer are not well-established. Over the
      past 2 decades, epidemiological studies on pancreatic cancer have been plagued
      with methodological issues associated with studying a highly fatal disease, and
      inconsistent findings have hindered our understanding of the etiology of
      pancreatic cancer. Although familial pancreatic cancer is well-documented, the
      genes responsible for this condition have not been identified and are unlikely to
      explain more than 5-10% of all pancreatic cancer cases. Chronic pancreatitis and
      diabetes mellitus are medical conditions that have been consistently related to
      pancreatic cancer. Data from numerous studies suggest that these conditions are
      likely to be causally related to pancreatic cancer, rather than being
      consequences of the cancer. Recent cohort studies, which are less prone to biases
      than case-control studies, suggest that obesity increases the risk of pancreatic
      cancer. Other studies support the hypothesis that glucose intolerance and
      hyperinsulinemia are important in the development of pancreatic cancer. Other
      potential risk factors include physical inactivity, aspirin use, occupational
      exposure to certain pesticides, and dietary factors such as carbohydrate or sugar
      intake.

PMID- 15238886
TI  - Palliation of pancreatic neoplasms.
AB  - Pancreatic adenocarcinoma accounts for 80% of pancreatic tumours. The majority
      are unresectable at diagnosis and only 10% of patients survive to 1 year.
      Therefore, selection of appropriate palliative procedures for jaundice, gastric
      outlet obstruction or pain is a vitally important aspect of the management of
      these patients. Overall survival is equivalent following surgical or non-surgical
      palliation of biliary obstruction. Operative biliary bypass is a more major
      intervention but is associated with longer relief of symptoms and fewer
      readmissions compared to non-operative procedures. Prognostic factors such as
      histopathology, presence of metastatic disease and C reactive protein levels may
      allow better prediction of survival, therefore aiding selection of the most
      appropriate palliative techniques.

PMID- 15238887
TI  - Surgical and endoscopic palliation for pancreatic cancer.
AB  - Patients with pancreatic cancer often present with locally advanced or metastatic
      disease and are deemed not to be candidates for a curative resection. Palliation
      in these patients focuses on relief of biliary obstruction, gastroduodenal
      obstruction and pain. Palliative treatment modalities include both surgical and
      nonsurgical approaches. Biliary obstruction is often initially treated with
      endoscopic biliary stenting. Two major types of biliary stents are used, plastic
      and metallic stents. Both of these provide similar initial relief of biliary
      obstruction, however, plastic stents have a greater propensity for occlusion and
      should primarily be used in patients with anticipated short survival duration.
      Metallic stents have a greater initial cost, but provide an overall cost-saving
      in patients with expected survival duration of over 6 months. Surgical palliation
      for biliary obstruction should be primarily considered in patients who fail
      endoscopic biliary decompression or who develop clinical evidence of
      gastroduodenal obstruction. In these patients, surgical palliation should consist
      of biliary decompression with a choledochojejunostomy when ever feasible, a
      gastroduodenal bypass and a chemical splanchnicectomy for pain relief. An initial
      prophylactic gastroenterostomy at the time of endoscopic biliary decompression is
      rarely indicated. The role of palliative pancreaticoduodenectomy remains
      controversial and to date there are no prospective randomized data to support its
      role in palliation of locally advanced pancreatic cancer. This review examines
      the available data from prospective trials for surgical and nonsurgical
      palliation of locally advanced and metastatic pancreatic cancer.

PMID- 15238888
TI  - Surgical palliation in pancreatic cancer.
AB  - The prognosis of patients with pancreatic carcinoma is poor. At the time of
      diagnosis, approximately 80% of patients are found to have an unresectable
      tumour, because of local spread or metastatic disease. Therefore, most patients
      will undergo palliative treatment, which is aimed at the improvement of the
      quality of life and the prevention of symptoms. The most important symptoms which
      are associated with advanced pancreatic cancer are pain, obstructive jaundice and
      gastric outlet obstruction. Controversy remains on the question whether these
      symptoms should be treated surgically or non-surgically. This review describes
      the best evidence (if possible randomised controlled trials) in recent literature
      on the palliation of most important symptoms and focuses on surgical palliative
      treatment options.

PMID- 15238889
TI  - Surgical techniques for pancreatic cancer.
AB  - Surgical resection of pancreatic adenocarcinoma offers the only chance for long
      term cure. Over the past 2 decades significant advances have been made in both
      the surgical techniques and the perioperative care of patients with pancreatic
      cancer. The operative management of pancreatic cancer involving the head, neck,
      and uncinate process consists of 2 phases: first, assessing tumor resectability
      and then, if the tumor is resectable, completing a pancreaticoduodenectomy and
      restoring gastrointestinal continuity. In this article, we describe our current
      techniques for resection of pancreatic cancer, review operative palliation for
      unresectable cancer, and discuss several controversies in the operative
      management of pancreatic cancer including: 1) the role of extended
      lymphadenectomy, 2) pylorus preservation and 3) pancreaticojejunostomy versus
      pancreaticogastrostomy for pancreatic duct reconstruction.

PMID- 15238890
TI  - Laparoscopic surgery for pancreatic tumors, an uptake.
AB  - Laparoscopy is not universally accepted as the best approach for pancreatic tumor
      disease. It is considered an elite surgical approach especially because of the
      technical difficulties involved; and the highly trained surgeons that are
      required to perform these operations. In addition, long operation times and lack
      of reduction in length of hospital stay press for the use of the laparotomic
      approach instead of a laparoscopic one. Four major areas of interest have been
      focused on: pancreaticoduodenectomy, pancreas resection and enucleation, the
      increasingly important areas of diagnostic laparoscopy for staging of pancreatic
      cancer and laparoscopic palliation of unresectable pancreatic cancer. A review of
      the literature about laparoscopic management of pancreatic tumors disease has
      been examined: 14 laparoscopic pancreaticoduodenectomies, 93 pancreatic
      resections, 41 enucleations, 4 left pancreatectomies and 2 hand assisted
      enucleations have been described since 1994. The laparoscopic distal pancreas
      resection and enucleation appear to be the best treatment option for lesions
      located in the body and tail of the gland; conversely laparoscopy may not be
      indicated for lesions located in the head of the gland. The laparoscopic approach
      today, does not present advantages in terms of post-operative outcome and
      operation times than the laparotomic approach. The hand assisted approach may be
      helpful in difficult cases to facilitate the operation; it permits an easier and
      safer dissection still conserving a minimally invasive approach. Moreover,
      laparoscopy is also becoming the best approach for tumor staging and palliation,
      and many surgeons use the laparoscopy to obtain the most information with the
      minimal damage in a situation already compromised by a weakening disease.

PMID- 15238891
TI  - Postoperative complications of pancreatic cancer surgery.
AB  - The incidence of ductal adenocarcinoma of the pancreas has been increasing
      worldwide in recent years. About 5% to 25% of all pancreatic cancers are
      resectable and only curatively resected patients enjoy a favourable outcome. But
      even in experienced centers a postoperative morbidity of 30-50% and a mortality
      around or underneath 5% is reported. As long term-survival is rare and
      complications are frequent the quality of life for the remaining months or years
      is of paramount importance. The most severe complications lead to reoperations,
      prolonged hospital stay, fatigue, and nutritional disorders thereby markedly
      compromising quality of life. Therefore, prevention and management of
      complications after pancreatic resections are reviewed. Prevention of disastrous
      complications is possible using a decent surgical technique and handling the soft
      pancreatic remnant in cancer patients carefully. The end-to-side, duct-to-mucosa
      anastomosis is the most preferred technique. The therapy of pancreatic leakage
      should be individualized and completion pancreatectomy should only be an option
      for recurrent hemorrhage, and a necrotic pancreatic stump. The continuous
      postoperative observation of the patient is of paramount importance to diagnose
      other severe complications, such as hemorrhage and septic complications, in time.
      Only early diagnosis and management of these complications can improve outcome
      and save life. Pancreaticoduodenectomy can be a safe procedure in experienced
      institutions, where the whole medical team is able to diagnose and treat these
      complications at any time.

PMID- 15238892
TI  - Pancreatic cystic tumors.
AB  - Cystic tumors of the pancreas are less frequent than other tumors in neoplastic
      pancreatic pathology, but in recent years the literature has reported an
      increasing number. After the first report by Becourt in 1830, cystic tumors were
      classified into 2 different types by Compagno and Oertel in 1978: benign tumors
      with glycogen-rich cells and mucinous cystic neoplasms with overt and latent
      malignancy. The WHO classification of exocrine tumors of the pancreas, published
      in 1996, is based on the histopathological features of the epithelial wall, which
      are the main factor in differential diagnosis with cystic lesions of the
      pancreas. Thanks to the knowledge acquired up to now, a surgical procedure is not
      always required because the therapeutic choice is conditioned by the correct
      classification of this heterogeneous group of tumors. Clinical signs are not
      really useful in the clinical work up, most patients have no symptoms and when
      clinical signs are present, they may help us to pinpoint the organ of origin but
      never to identify the type of pathology. In the last few years, the great
      improvement in imaging has enabled us not only to discriminate cystic from solid
      lesions, but also to identify the features of the lesions and label them
      preoperatively. More invasive diagnostic procedures such as fine needle
      aspiration and intracystic fluid tumor marker level are not really useful because
      they are not sensitive and the cystic wall can show different degrees of
      dysplasia and de-epithelialization. These are the reasons for sending the entire
      specimen to pathology. Good cooperation between surgeons, pathologists,
      radiologists and gastroenterologists is mandatory to increase the chances of
      making a proper diagnosis. Therefore, we must analyze all the information we
      have, such as age, sex, clinical history, location of the tumor and radiological
      features, in order to avoid the mistake of treating a cystic neoplasm as a benign
      lesion or as a pseudocyst, as described in the literature. Except for inoperable
      cases due to the critical condition of the patient or non-resectable lesions,
      surgical treatment differs with the diagnosis. Cystic tumors of the pancreas,
      therefore, are a heterogeneous group of tumors, with a real problem regarding
      differential diagnosis between neoplastic and inflammatory lesions. Even with a
      proper work up, some perplexity may remain about the nature of the lesion and in
      these cases the surgical procedure has a therapeutic value as well as playing a
      diagnostic role. The role of surgery is central in the treatment of these tumors
      because it could be curative when complete resection is possible. In this way,
      the lack of good therapeutic results with chemotherapy and radiotherapy force the
      surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms
      represent a new and, from the epidemiological point of view, important chapter in
      the world of cystic tumors. The margin of resection is important and the surgeon
      has to be aware that in order to have a curative resection, total pancreatectomy
      is sometimes required. In the last few years the therapeutic approach has changed
      thanks to new knowledge of the biological behavior of these tumors. In fact, from
      a surgical approach in all cases, we are now discussing the possibility of a
      follow-up not only for asymptomatic serous cystadenomas but also for the little
      branch side intraductal papillary mucinous neoplasms (IPMNs) in critical
      patients. A follow-up could be planned even for solid pseudopapillary tumors but
      it seems risky to leave untreated big tumors in young patients without a certain
      diagnosis and with so few studies reported in the literature.

PMID- 15238893
TI  - Pediatric workforce projections and unintended consequences.

PMID- 15238894
TI  - The obesity epidemic: family matters.

PMID- 15238895
TI  - Another small step in the path to controlling micronutrient deficiencies...but we
      still have a long way to go.

PMID- 15238896
TI  - Cystic fibrosis lung disease: when does it start, and how can it be prevented?

PMID- 15238897
TI  - Health-related quality of life: developmental and psychometric issues.

PMID- 15238899
TI  - Time to get on the potty: Are constipation and stool toileting refusal causing
      delayed toilet training?

PMID- 15238898
TI  - The continuing conundrum of sedation for painful and nonpainful procedures.

PMID- 15238900
TI  - World Report on Violence and Health: what it means for children and
      pediatricians.

PMID- 15238901
TI  - Risk factors for childhood overweight: a prospective study from birth to 9.5
      years.
AB  - OBJECTIVES: To ascertain risk factors for the development of overweight in
      children at 9.5 years of age. STUDY DESIGN: This was a prospective study of 150
      children from birth to 9.5 years of age, with assessment of multiple hypothesized
      risk factors drawn from research reports. RESULTS: Five independent risk factors
      for childhood overweight were found. The strongest was parent overweight, which
      was mediated by child temperament. The remaining risk factors were low parent
      concerns about their child's thinness, persistent child tantrums over food, and
      less sleep time in childhood. Possible mechanisms by which each of these factors
      influence weight gain are outlined. Two different pathways to childhood
      overweight/obesity were found, depending on degree of parental overweight.
      CONCLUSIONS: There is evidence of considerable interaction between parent and
      child characteristics in the development of overweight. Several of the identified
      risk factors are amenable to intervention possibly leading to the development of
      early prevention programs.

PMID- 15238902
TI  - Bioavailability of iron and zinc from a multiple micronutrient-fortified
      beverage.
AB  - OBJECTIVE: To test the hypothesis that micronutrient beverages can provide the
      daily iron and zinc needs of small children. STUDY DESIGN: Forty children aged 6
      to 9 years were recruited (Lima, Peru). For 4 weeks, they received a daily
      serving of a beverage containing multiple micronutrients. Over 2 consecutive
      days, subjects received stable isotope-labeled servings of the beverage with and
      without a meal as well as an intravenous dose of zinc. Iron and zinc
      bioavailability were assessed using mass spectrometry. RESULTS: Iron absorption
      was significantly lower with a meal than without (9.8 +/- 6.7% versus 11.6 +/-
      6.9%, P=.04), but zinc absorption was not (24.5 +/- 10.7% versus 22.8 +/- 7.6%,
      P=.2). In either case, however, a single daily serving provided most of the iron
      and zinc requirements for the children. CONCLUSIONS: Single daily servings of
      multinutrient-fortified beverages can meet much of the mineral needs for small
      children. Food has a small inhibitory effect on iron, but not zinc, absorption;
      therefore, these beverages can be efficacious even when given with a meal.

PMID- 15238903
TI  - High-resolution computed tomography in young patients with cystic fibrosis:
      distribution of abnormalities and correlation with pulmonary function tests.
AB  - OBJECTIVE: To assess pulmonary abnormalities detected by high-resolution computed
      tomography (HRCT) in young children with cystic fibrosis (CF) and mild to
      moderate lung disease. STUDY DESIGN: High-resolution computed tomography was
      performed in 60 children, 6 to 10 years old, with mild to moderate lung disease
      (forced expiratory volume in 1 minute [FEV(1)], 52-137; mean, 102; SD, 15%
      predicted). HRCTs were scored by using a system that evaluates each lobe for
      severity and extent of CF lung disease. Findings of CF lung disease were
      tabulated in all subjects and in a subgroup with normal pulmonary function tests.
      HRCT scores were correlated with FEV(1), forced vital capacity (FVC), and forced
      expiratory flow between 25% and 75% of expired vital capacity (FEF(25-75)) in 57
      patients. RESULTS: Bronchiectasis was present in 35% of subjects, mucous plugging
      in 15%, and air trapping in 63%. No abnormality was detected in 25%. In 37
      subjects with FEV(1), FVC, and FEF(25-75) >85% predicted, bronchiectasis was
      present in 30%. In 17% of these subjects, bronchiectasis was seen in > or =4
      lobes. Correlations between HRCT scores and FEV(1) were significant and showed
      fair to moderate correlation (r=0.36-0.46). CONCLUSIONS: High-resolution computed
      tomography demonstrated a broad range of pulmonary abnormalities in young
      patients with CF with mild to moderate lung disease. In this study,
      abnormalities, including bronchiectasis, were common in young children with CF
      and normal pulmonary function tests.

PMID- 15238904
TI  - The Minneapolis-Manchester Quality of Life instrument: Reliability and validity
      of the Youth Form.
AB  - OBJECTIVE: Improvements in survival after childhood cancer have increased
      emphasis on health-related quality of life (HRQoL) of survivors. We developed the
      Minneapolis-Manchester Quality of Life-Youth Form (MMQL-YF) as a standardized
      patient self-report instrument designed to assess HRQoL in childhood cancer
      survivors between the ages of 8 and 12 years. STUDY DESIGN: To validate the
      instrument, the MMQL-YF was administered to 643 children (481 healthy, 162 with
      cancer). Factor analysis was conducted to refine the instrument, and Cronbach's
      alpha coefficient was used to measure its internal reliability. Known-groups
      validity was determined by comparing healthy children with those with cancer.
      Construct validity was studied by a comparison of similar domains in the MMQL-YF
      and the Child Health Questionnaire (CHQ). Stability was tested by re
      administration of the MMQL-YF 2 weeks later. RESULTS: Internal consistency
      reliability was in the acceptable range for this instrument. The MMQL-YF was able
      to distinguish between known groups, and its scales correlated highly with
      similar CHQ domains. Test-retest reliability showed that the instrument was
      extremely stable in all scales tested. CONCLUSION: Data provide evidence for the
      validity and reliability of the MMQL-YF as a comprehensive, multidimensional,
      self-report instrument for measuring HRQoL among childhood cancer survivors.

PMID- 15238906
TI  - A pediatric sedation/anesthesia program with dedicated care by anesthesiologists
      and nurses for procedures outside the operating room.
AB  - OBJECTIVE: To examine the performance of a pediatric sedation team working
      according to a specific protocol and to assess parental satisfaction with the
      service. STUDY DESIGN: A descriptive observational study of all procedures
      performed by the sedation team (comprising sedation-trained pediatric intensive
      care nurses and dedicated anesthesiologists) in a university hospital over 6
      years. Data collected included demographics, procedure and location, sedation
      staff present, sedation failure, drugs used, requirements for escalation of
      sedation, complications, and parental satisfaction. RESULTS: Sedation was
      provided for 8760 procedures in 5554 children. The sedation nurse started 1769
      (20%) procedures using triclofos sodium and required the assistance of the
      anesthesiologist in 115 (6.5%) cases. The remaining 6991 (80%) cases were
      performed by the anesthesiologist, predominantly using propofol (in 72.5% of
      cases). No cases were deferred as a result of insufficient sedation. Adverse
      events were recorded in 153 (1.7%) children. Of these, 132 (86%) were mild
      decreases in oxygen saturation. Three children were not discharged as a result of
      oversedation. Feedback indicated that 95% of parents were very satisfied with the
      sedation service. CONCLUSION: A dedicated sedation team using a written protocol
      provides a service with minimal case cancellation, zero sedation failure, very
      good safety, and excellent parental satisfaction.

PMID- 15238907
TI  - Optimal management of phenylketonuria: a centralized expert team is more
      successful than a decentralized model of care.
AB  - OBJECTIVE: To compare phenylketonuria (PKU) management by a centralized, expert
      team in the Province of Nova Scotia (NS) with the decentralized approach in New
      Brunswick (NB). STUDY DESIGN: Retrospective chart review documented frequency of
      outpatient visits, phenylalanine (Phe) concentration, and medical formula use.
      Structured telephone interviews with the 8 regional NB dietitians (NB-D)
      documented their knowledge and support in PKU management. Patients with PKU
      (n=108; age, birth to 42 years) reside in NB (n=69) and NS (n=39). More were lost
      to contact in NB than in NS (9/69 vs 1/39) and more were completely off diet in
      NB than in NS (24/60 vs 1/38, P=.05). All 15 children <2 years old followed by a
      PKU team in either NS or Saint John, NB had optimal Phe levels. Children 2 to 12
      years of age in NS had better Phe control and more medical visits than in NB (P
      <.01). Older patients had more episodes of elevated Phe levels (P=.01). Formula
      was dispensed in appropriate yearly amounts to 52% in NB and >95% in NS. Mental
      handicap or borderline intelligence was common in both NB (44%) and NS (42%). All
      NB-D wished additional specialized medical, nursing, or social work assistance.
      CONCLUSIONS: PKU management appears to be more effective with an expert,
      coordinated team approach.

PMID- 15238908
TI  - Safety of DTaP-based combined immunization in very-low-birth-weight premature
      infants: frequent but mostly benign cardiorespiratory events.
AB  - OBJECTIVE: To evaluate the safety of diphtheria-tetanus-acellular pertussis
      inactivated polio-Haemophilus influenzae type B (DTaP-IPV-HIB) immunization in
      premature infants. STUDY DESIGN: Observational study of 78 very low birth weight
      premature infants (mean gestational age, 28+/-2 weeks; mean birth weight, 1045+/
      357 g) given DTaP-IPV-HIB vaccine before hospital discharge. Apnea, bradycardia,
      oxygen requirements and saturation, feeding practice, and medical interventions
      were assessed before and after immunization. The results were analyzed by the
      severity of the clinical condition and the persistence of prematurity-associated
      symptoms. RESULTS: Administration of DTaP-IPV-HIB elicited resurgence or increase
      in cardiorespiratory events in 47% of infants (15% had apnea, 21% had
      bradycardia, 42% of desaturations). Most vaccine-triggered events resolved
      spontaneously or after brief stimulation. The relative risk was 5- to 8-fold
      higher in infants with a severe clinical course or persistence of
      cardiorespiratory symptoms at the time of immunization. Bag-mask respiratory
      support was given to 5 of 78 infants, and O(2) requirements increased transiently
      in 4 of 21 infants with chronic lung disease, none requiring reventilation.
      Reintroduction of O(2) supplementation, interruption of active oral feeding, or
      postponing of hospital discharge was not required. CONCLUSIONS: Cardiorespiratory
      events were frequently increased after DTaP-IPV-HIB immunization, requiring
      monitoring and appropriate intervention. However, these episodes did not have
      detrimental impact on the infants' clinical course. Timely immunization is
      warranted even in the most vulnerable preterm infants.

PMID- 15238909
TI  - Duration of intubation attempts during neonatal resuscitation.
AB  - OBJECTIVE: Since the American Academy of Pediatrics Neonatal Resuscitation
      Program recommends that intubation should be completed in approximately 20
      seconds, we measured the duration of neonatal intubation attempts by different
      operators, using video recordings of neonatal resuscitations. STUDY DESIGN: We
      used an ongoing quality improvement program to measure the duration of intubation
      attempts. RESULTS: The mean duration for the 50 successful intubations, including
      6 for meconium, was 27.3 seconds compared with 29.8 seconds for unsuccessful
      attempts (not significant). Fifteen infants were successfully intubated on each
      of the first and second attempts, 10 on the third attempt, and 10 required more
      than 3 attempts. The mean duration of successful intubation was 31.9 seconds for
      PL-1's, 27.5 seconds for PL-2/3's, and 23.6 seconds for fellows. Overall
      intubations were more successful for a duration of 30 seconds or less compared
      with 20 seconds or less (72% vs 38%; chi(2)=10.3, P=.001). No infant
      decompensated between 20 and 30 seconds. Ten successful and 12 failed attempts
      took longer than 40 seconds. CONCLUSIONS: We recommend that a duration of 30
      seconds is a reasonable guideline for neonatal intubation during resuscitation.

PMID- 15238910
TI  - Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal
      gynecomastia.
AB  - OBJECTIVES: To assess the efficacy of the anti-estrogens tamoxifen and raloxifen
      in the medical management of persistent pubertal gynecomastia. STUDY DESIGN:
      Retrospective chart review of 38 consecutive patients with persistent pubertal
      gynecomastia who presented to a pediatric endocrinology clinic. Patients received
      reassurance alone or a 3- to 9-month course of an estrogen receptor modifier
      (tamoxifen or raloxifene). RESULTS: Mean (SD) age of treated subjects was 14.6
      (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in
      breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment
      with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some
      improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving
      raloxifene, but a greater proportion had a significant decrease (>50%) with
      raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients.
      CONCLUSION: Inhibition of estrogen receptor action in the breast appears to be
      safe and effective in reducing persistent pubertal gynecomastia, with a better
      response to raloxifene than to tamoxifen. Further study is required to determine
      that this is truly a treatment effect.

PMID- 15238911
TI  - Lipid abnormalities in children with types A and B Niemann Pick disease.
AB  - OBJECTIVE: To characterize the lipid profiles in patients with types A and B
      Niemann Pick disease (NPD) and determine if lipid abnormalities are associated
      with evidence of early cardiovascular disease or correlate with genotype. STUDY
      DESIGN: The study was a cross-sectional analysis of 10 patients with NPD type A
      and 30 patients with NPD type B that was carried out in the General Clinical
      Research Center. For each patient, fasting lipid profile and glucose, T4, height
      or length, weight, resting blood pressure, and acid sphingomyelinase deficiency
      genotype were measured. In type B patients, electrocardiograhic-gated helical
      computed tomography of the heart also was obtained. RESULTS: Lipid abnormalities
      included low (<35 mg/dL) high-density lipoprotein cholesterol in 100% of patients
      and hypertriglyceridemia and increased low-density lipoprotein cholesterol in 62%
      (25/40) and 67% (27/40) of patients, respectively. Coronary artery calcium scores
      were positive (>1.0) in 10 of 18 type B patients studied. There was no
      correlation of the Delta R608 genotype with a milder phenotype for the lipid
      abnormalities, as has been observed for a number of other NPD manifestations.
      CONCLUSIONS: Lipid abnormalities are part of the phenotype in types A and B NPD
      and may be associated with early atherosclerotic heart disease.

PMID- 15238912
TI  - Pathophysiologic basis for growth failure in children with ichthyosis: an
      evaluation of cutaneous ultrastructure, epidermal permeability barrier function,
      and energy expenditure.
AB  - OBJECTIVE: Because an impaired epidermal permeability barrier is present in many
      of the ichthyoses, we examined the contribution of barrier failure to caloric
      requirements in children with ichthyosis and growth failure. STUDY DESIGN:
      Transepidermal water loss (TEWL) and ultrastructural parameters of the
      permeability barrier were evaluated in 10 hospitalized children with ichthyosis
      and growth failure. Nutritional intake, resting energy expenditure, and calories
      lost as heat of evaporation were determined. RESULTS: Mean basal TEWL rates were
      markedly elevated in all study patients in comparison to the expected upper limit
      of normal (39.6+/-20.6 vs 8.7 mL/m(2) per hour). The severity of abnormalities in
      the ultrastructure of permeability barrier-related structures, assessed
      semiquantitatively, correlated significantly to mean basal TEWL rates (P <.001).
      Total body daily TEWL was elevated (746 +/- 468 vs 209 mL/d), resulting in a
      caloric drain of 433 +/- 272 kcal/d (21 +/- 9.8 kcal/kg per day) through heat of
      evaporation. Nutrient intake exceeded requirements in all, but resting energy
      expenditure exceeded predicted in 5 of 6 patients and correlated significantly
      with mean basal TEWL rates (P <.005). CONCLUSIONS: A defective permeability
      barrier in children with ichthyosis can result in ample chronic losses of water
      and calories to impair growth.

PMID- 15238914
TI  - The renin angiotensin system in childhood hypertension: selective increase of
      angiotensin-(1-7) in essential hypertension.
AB  - OBJECTIVE: We examined the activity of the renin-angiotensin system (RAS) in
      normotensive and hypertensive children. STUDY DESIGN: Hypertensive patients (12
      with renovascular hypertension and 15 with essential hypertension) and 32
      normotensive subjects were evaluated at a Pediatric Nephrology Center. Blood
      samples for plasma renin activity (PRA) and angiotensin peptides measurements
      were obtained once from normotensive subjects and before and after treatment from
      hypertensive patients. Plasma samples were extracted using Bond-Elut cartridges
      (Analytichem International, Harbor City, Calif), and peptide concentrations were
      determined by radioimmunoassay (RIA). RESULTS: PRA, Angiotensin I (Ang I),
      Angiotensin II (Ang II), and Angiotensin-(1-7) [Ang-(1-7)] levels were
      significantly higher in renovascular hypertensive patients than in normotensive
      children (3.3 +/- 1.2 vs 0.40 +/- 0.22 ng Ang I/mL/hour, 81.4 +/- 24.8 vs 26.4 +/
      13.4 pg/mL, 59.3 +/- 17.0 vs 21.4 +/- 8.7 pg/mL, 41.0 +/- 10.5 vs 16.2 +/- 7.9
      pg/mL, respectively). The surgical treatment normalized blood pressure, PRA, and
      angiotensins levels. In contrast with renovascular disease, only Ang-(1-7) levels
      were significantly increased in essential hypertensive patients compared with
      normotensive (78.8 +/- 22.8 vs 16.2 +/- 7.9 pg/mL). Treatment with calcium
      channel blockers did not alter the RAS measurements. CONCLUSION: Our data show
      different RAS profiles in childhood hypertension and suggest a blood pressure
      independent change of Ang-(1-7) in essential hypertension.

PMID- 15238915
TI  - Vitamin A status, hospitalizations, and other outcomes in young children with
      sickle cell disease.
AB  - OBJECTIVE: To determine the relation of serum vitamin A status to growth,
      nutritional and hematologic status, and to the number of hospitalizations in
      children with sickle cell disease-SS (homozygous for the S allele, SCD-SS). STUDY
      DESIGN: Children (2-9.9 years of age) with SCD-SS were assessed for serum
      retinol, hemoglobin, hematocrit, reticulocyte count, height, weight, body mass
      index, and recalled dietary intake. Vitamin A status was defined on the basis of
      serum retinol concentration as suboptimal (<30 microg/dL) and normal (> or =30
      microg/dL). Hospitalizations were determined for 1 year after vitamin A
      assessment. RESULTS: Mean serum retinol was 26.7 +/- 6.8 microg/dL in 66 subjects
      (39 girls) and was suboptimal in 66% of children. Compared with those with normal
      status, children with suboptimal vitamin A had significantly lower body mass
      index z score (-0.7 +/- 1.0 vs -0.1 +/- 0.6) and hemoglobin (7.9 +/- 1.1 vs 8.5
      +/- 1.1), and hematocrit (23.3 +/- 3.0 vs 25.1 +/- 3.8) and significantly more
      hospitalizations (2.8 +/- 2.0 vs 0.7 +/- 0.8). After adjusting for age and sex,
      suboptimal vitamin A status was associated with a 10-fold increased risk for
      hospitalization (OR, 10.5; 95% CI, 2.3, 48.6) and with increased pain (OR,5.3;
      95% CI, 1.3, 21.6) and fever episodes (OR, 6.4; 95% CI, 1.7, 24.9) requiring
      hospitalization. CONCLUSIONS: Suboptimal vitamin A status was prevalent in US
      children with SCD-SS and was associated with increased hospitalizations and poor
      growth and hematologic status.

PMID- 15238916
TI  - Why is toilet training occurring at older ages? A study of factors associated
      with later training.
AB  - Recent studies suggest that children are completing toilet training much later
      than the preceding generation. Our objective was to identify factors associated
      with later toilet training. Children between 17 and 19 months of age (n=406) were
      enrolled in the study. At enrollment, parents completed the Parenting Stress
      Index and the Receptive-Expressive Emergent Language Scale. Follow-up parent
      interviews were conducted every 2 to 3 months until children completed daytime
      toilet training. Information obtained at follow-up interviews included steps
      parents were taking to toilet train their child, child toilet training behaviors,
      presence and frequency of constipation, birth of a sibling, and child care
      arrangements. In a stepwise linear regression model predicting age at completion
      of toilet training, 3 factors were consistently associated with later training:
      initiation of toilet training at an older age, presence of stool toileting
      refusal, and presence of frequent constipation. Models including these variables
      explained 25% to 39% of the variance in age at completion of toilet training. In
      conclusion, a later age at initiation of toilet training, stool toileting
      refusal, and constipation may explain some of the trend toward completion of
      toilet training at later ages.

PMID- 15238917
TI  - Validation of a novel real time 13C urea breath test for rapid evaluation of
      Helicobacter pylori in children and adolescents.
AB  - We prospectively evaluated a (13)C urea breath test (UBT) that involves passive
      continuous sampling for diagnosis of Helicobacter pylori in 72 children. Results
      were obtained within 10 minutes in 96% of patients. The test is rapid, user
      friendly, and has 100% concordance with conventional diagnostic methods.

PMID- 15238918
TI  - Airway eicosanoids in acute severe respiratory syncytial virus bronchiolitis.
AB  - We prospectively studied the levels of eicosanoids in intubated patients with
      severe bronchiolitis and compared them to electively intubated non-infected
      infants. LeukotrieneE(4) (LTE(4)), leukotrieneB(4) (LTB(4)), and
      prostaglandinE(2) (PGE(2)) levels were significantly increased (P <.01) from
      endotracheal (ET) aspirates of infants with bronchiolitis compared with controls,
      as were urinary LTE(4) levels (P <.001). We conclude that eicosanoids are
      increased in the tracheal aspirates and urine of children with bronchiolitis.

PMID- 15238919
TI  - Variable clinical expression of an identical mutation in the ATP7A gene for
      Menkes disease/occipital horn syndrome in three affected males in a single
      family.
AB  - Two maternal half-brothers presented with huge cephalic hematoma, fatal in one.
      Skin morphology disclosed lack of elastic fibres. Their maternal uncle is
      moderately mentally handicapped and has extensive connective tissue disorders. In
      all these patients, an identical missense mutation in the ATP7A gene was found
      and confirmed Menkes' disease.

PMID- 15238921
TI  - Fanconi anemia in a neonate with pancytopenia.
AB  - We report the case of a newborn infant with Fanconi anemia with congenital
      thrombocytopenia and development of pancytopenia during the neonatal period. The
      boy showed no malformations characteristic for Fanconi anemia.

PMID- 15238920
TI  - Pancreatic enzyme elevations in children with diabetic ketoacidosis.
AB  - The incidence of pancreatic enzyme elevations in children with diabetic
      ketoacidosis (DKA) compared with children with newly diagnosed diabetes without
      DKA was assessed in a prospective study. Pancreatic enzyme elevations,
      particularly hyperlipasemia, are common but not associated with significant
      symptomatology. Acute pancreatitis was diagnosed in 2% of children with DKA.

PMID- 15238923
TI  - Decreased final height of children with growth deceleration secondary to poor
      weight gain during late childhood.
AB  - Eighteen healthy, short children with normal growth during most of their
      childhood were evaluated after a sustained fall in weight and reduced linear
      growth. Growth was followed after nutritional counseling until final height. This
      report demonstrates the need for an appropriate-for-age weight gain in growing
      children as a relatively minor but prolonged caloric restriction, leading to a
      sustained fall in weight centiles, will affect growth velocities long term and
      may lead to reduced final heights.

PMID- 15238924
TI  - Syringocystadenoma papilliferum: an unusual cutaneous lesion in a pediatric
      patient.
AB  - We report a case of syringocystadenoma papilliferum, a rare cutaneous adnexal
      neoplasm, occurring synchronously in two distinct unusual locations in a 22-month
      old child with lesions on the lower leg and back.

PMID- 15238925
TI  - Congenital cutaneous mastocytosis.

PMID- 15238926
TI  - Efficacy and safety of echinacea in treating upper respiratory tract infections
      in children: a randomized controlled trial.

PMID- 15238927
TI  - Penicillin for acute sore throat in children: randomised, double blind trial.

PMID- 15238928
TI  - Oral prednisolone in the acute management of children age 6 to 35 months with
      viral respiratory infection-induced lower airway disease: a randomized, placebo
      controlled trial.

PMID- 15238929
TI  - Evidence assessment of the accuracy of methods of diagnosing middle ear effusion
      in children with otitis media with effusion.

PMID- 15238930
TI  - Randomized clinical trial of docusate, triethanolamine polypeptide, and
      irrigation in cerumen removal in children.

PMID- 15238944
TI  - Excisional surgery of periocular angiosarcoma.

PMID- 15238946
TI  - De-QUORUM.

PMID- 15238945
TI  - Limbal stem cell deficiency and xeroderma pigmentosum: a case report.

PMID- 15238947
TI  - Understanding the jigsaw of evidence-based dentistry. 2. Dissemination of
      research results.

PMID- 15238948
TI  - Benefits of topical fluorides firmly established.

PMID- 15238949
TI  - Topical fluorides provide additional benefit when used with fluoride toothpaste.

PMID- 15238950
TI  - Water fluoridation and Down's syndrome evidence inconclusive.

PMID- 15238951
TI  - Effectiveness of screening for oral cancer not proven.

PMID- 15238952
TI  - Legitimate to extrapolate efficacy from one pain context to another.

PMID- 15238954
TI  - No strong or consistent association between early childhood caries and pacifier
      use.

PMID- 15238953
TI  - Lack of reliable clinical evidence for or against direct and indirect veneers.

PMID- 15238955
TI  - Survival rates similar with full cast crowns and direct composite restorations.

PMID- 15238956
TI  - Is penicillin prophylaxis effective against bacterial endocarditis?

PMID- 15238961
TI  - A systematic review of retrograde filling materials.

PMID- 15238963
TI  - Evidence-based guidelines.

PMID- 15238964
TI  - Understanding the jigsaw of evidence-based dentistry: 1. Introduction, research
      and synthesis.

PMID- 15238965
TI  - Virtual centre for improving oral health--vC-IOH.

PMID- 15238966
TI  - Clinical practice guideline on emergency management of acute apical periodontitis
      (AAP) in adults.

PMID- 15238967
TI  - Studies suggest alternatives to amalgam as a retrograde filling material for
      apicectomy.
AB  - DATA SOURCES: Sources were Medline and the Cochrane Library. STUDY SELECTION:
      Studies included were in vivo with human subjects, had experimental and control
      groups, and gave quantitative results in English, German or French. DATA
      EXTRACTION AND SYNTHESIS: Success and failure rates were derived from randomised
      controlled trials (RCT), clinical controlled trials (CCT), cohort studies (CS)
      and case-controlled studies (CCS). Qualitative synthesis of results was
      performed. RESULTS: Two RCT, six CCT and 14 CCS were identified. The two RCT
      suggest that glass ionomer may be more effective than amalgam, conversely one CCT
      showed amalgam to be more effective. CCTs also suggest that EBA (reinforced zinc
      oxide eugenol) cement, composite with GLUMA (Bayer AG., Leverkusen, Germany) and
      gold leaf retrograde filling may be more effective than amalgam. A further CCT
      suggested that gutta-percha used as a retrograde filing is less effective than
      when used following an orthograde approach. CONCLUSIONS: Based on the outcome of
      two RCT, glass ionomer appears as effective as amalgam. EBA cement, composite
      with GLUMA and gold leaf and orthograde gutta-percha may also be as effective as
      amalgam. Evidence is limited, however, and further research is needed.

PMID- 15238968
TI  - Orthodontic outreach clinics--no marked advantages or disadvantages.
AB  - DESIGN: Single centre randomised controlled trial. INTERVENTION: Allocation of
      referred patients to outreach or main base consultation appointments. OUTCOME
      MEASURE: The outcome of consultation, the cost and duration of the visit and the
      carer/patient's perceptions of the visit. RESULTS: There were no differences in
      outcome of the consultation. While consumer travel costs and the duration of
      appointments were significantly higher for the main base clinics, these
      differences were not great. However, consumers preferred to attend an appointment
      in an outreach clinic. CONCLUSIONS: There do not appear to be marked advantages
      or disadvantages in providing consultation appointments for orthodontics in
      outreach clinics.

PMID- 15238969
TI  - Postal reminders can improve attendance at orthodontic clinics.
AB  - DESIGN: A randomised controlled trial in an NHS hospital orthodontic clinic.
      INTERVENTION: Participants either received an appointment or an appointment plus
      a reminder at least 2 weeks before their appointment. The reminder letter was
      sent with a stamped addressed postcard, which the patient was asked to return, to
      confirm the appointment. OUTCOME MEASURE: Patient attendance at the clinic.
      RESULTS: A total of 231 patients were entered into the study. Patients who
      received a reminder and returned the confirmation were significantly less likely
      to fail the appointment than those who did not receive a reminder. 27% of girls
      failed appointments compared with 15% of boys. Those from areas of high social
      deprivation were more likely to fail to attend appointment than people who were
      more affluent. CONCLUSIONS: The use of postal reminders for orthodontic
      consultation appointments appears to result in a useful increase of appointments
      that are kept or cancelled in advance but does not counteract the effect of
      social deprivation on attendance.

PMID- 15238970
TI  - Dental health educators in general practice have small impact.
AB  - DESIGN: A cluster randomised, controlled clinical trial of two years' duration.
      INTERVENTION: Test group were given visits to a dental health educator over a 2
      year period to counsel mothers of at-risk, pre-school children. OUTCOME MEASURE:
      Caries prevalence of the children and dental health knowledge, attitudes and
      toothbrushing skills of the parents. The full costs of the exercise were kept
      throughout. RESULTS: After 2 years, 271 (81%) children and 248 (92%) mothers
      remained in the study. There was an 18% difference in mean dmft between the
      groups in favour of the test group children but this was not statistically
      significant. CONCLUSIONS: The model tested of seconding a qualified dental health
      educator to general dental practices to counsel mothers of regularly attending,
      at-risk, young children failed to reveal a substantial improvement in dental
      health over a 2-year period. However, there were clear benefits in relation to
      dental health knowledge, attitudes and toothbrushing skills among these mothers.

PMID- 15238971
TI  - Hypotensive anaesthesia and blood loss in orthognathic surgery.
AB  - OBJECTIVE: This trial aimed to determine whether hypotensive anaesthesia reduces
      blood loss during orthognathic surgery. DESIGN: Randomised trial. INTERVENTION:
      Subjects were allocated to hypotensive (24 patients) or normotensive (29
      patients) groups, assigned by sealed envelope, before undergoing standard
      orthognathic procedure. OUTCOME MEASURE: Median blood loss was measured. RESULTS:
      A significant reduction in blood loss was seen with hypotensive anaesthesia.
      CONCLUSIONS: There was pronounced reduction in blood loss during orthognathic
      procedures carried out under hypotensive anaesthesia.

PMID- 15238972
TI  - The quality of systematic reviews in dentistry.
AB  - DATA SOURCES: Sources of reviews were the Database of Reviews of Effectiveness
      (DARE) and completed systematic reviews registered by the Cochrane Oral Health
      Group in the Cochrane Library. STUDY SELECTION: All systematic reviews that
      examined the effectiveness of interventions for oral, dental and craniofacial
      disorders and diseases were eligible for inclusion. DATA EXTRACTION AND
      SYNTHESIS: A quality assessment checklist was completed for each study. RESULTS:
      A total of 115 studies were identified, of which 65 were relevant to the review.
      The area most frequently evaluated within the reviews was pain relief or
      prevention (20 out of 65, ie, 31%) followed by caries, and oral medicine. The
      quality assessment of the systematic reviews identified highlighted key areas
      where improvements could be made. One major weakness was that the search
      strategies employed in reviews were not always adequate: only 12 reviews (19%)
      demonstrated an attempt to identify all relevant studies. Other areas of weakness
      include the screening and quality assessment of primary studies, the pooling of
      data and examination of heterogeneity, and the interpretation of findings.
      CONCLUSIONS: The quality of systematic reviews in dentistry could be improved. If
      future clinical decisions are to be based upon systematic reviews, it is
      imperative that reviews address clinically-relevant, focused questions, and
      follow a transparent, well-designed protocol.

PMID- 15238978
TI  - Targeting the epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) is a member of the erbB family of
      tyrosine kinase receptors (RTK). The EGFR is involved in cell proliferation,
      metastasis and angiogenesis, and is expressed in a large proportion of epithelial
      tumours. The two main classes of EGFR inhibitors in clinical trials are the RTK
      inhibitors and the monoclonal antibodies. The clinical development of EGFR
      inhibitors has introduced new challenges to the design of phase I, II, and III
      trials. Both classes of agents can be safely administered at doses sufficient to
      inhibit the EGFR system. Receptor tyrosine kinase inhibitors have been
      extensively evaluated in non-small-cell lung cancer. In this setting, gefitinib
      has demonstrated activity in patients who fail initial chemotherapy. Monoclonal
      antibodies have been developed in combination with cytotoxic chemotherapy in
      several tumour types, most notably colorectal and head and neck cancer. The
      preliminary results suggest an increase in response rate and time to progression
      with the combination of cetuximab and chemotherapy in both disease models. Future
      issues in the development of EGFR inhibitors include the identification of
      biologic predictors of response, combination with other targeted agents, and
      their utilisation in earlier stage malignancies.

PMID- 15238979
TI  - Psychological problems of cancer patients: a cancer distress screening with a
      cancer-specific questionnaire.
AB  - The purpose of this study was to assess the psychological distress of cancer
      patients in a disease-specific manner as well as the demographic and medical
      variables that have an impact on the distress. Psychological distress was
      assessed with the Questionnaire on Stress in Cancer Patients revised version,
      which has been developed and psychometrically evaluated in Germany. It consists
      of items about 23 cancer-specific stress situations, which have to be answered in
      terms of relevance and amount of distress. A heterogeneous sample of 1721 cancer
      in- and outpatients was assessed. For the total group, the most important
      distress is the fear of disease progression. We consider between 23.4% (ca. of
      the upper gastrointestinal tract) and 40.9% (breast cancer patients) as highly
      distressed. The most distressed diagnostic subgroups are patients with soft
      tissue tumours and breast cancer patients. There are no global (general) stress
      factors, as the relevant demographic and medical 'risk factors' varied between
      the diagnostic subgroups. Cancer-specific distress questionnaires give a more
      precise insight into patients' experience than general or psychiatric
      questionnaires. They are not only used in large screening studies but also in
      routine medicine, particularly when the objective is to identify patients to whom
      psycho-oncological support is to be given.

PMID- 15238980
TI  - Underexpression of peroxisome proliferator-activated receptor (PPAR)gamma in
      PAX8/PPARgamma-negative thyroid tumours.
AB  - The expression of peroxisome proliferator-activated receptor (PPAR)gamma in
      thyroid neoplasias and in normal thyroid (NT) tissues has not been fully
      investigated. The objectives of the present work were: to study and compare the
      relative expression of PPARgamma in normal, benign and malignant thyroid tissues
      and to correlate PPARgamma immunostaining with clinical/pathological features of
      patients with thyroid cancer. We analysed the expression of PPARgamma in several
      types of thyroid tissues by reverse transcription-polymerase chain reaction (RT
      PCR), interphase fluorescent in situ hybridisation, real-time RT-PCR and
      immunohistochemistry. We have demonstrated that NT tissues express PPARgamma both
      at mRNA and at protein level. PAX8-PPARgamma fusion gene expression was found in
      25% (six of 24) of follicular thyroid carcinomas (FTCs) and in 17% (six of 36) of
      follicular thyroid adenomas, but in none of the 10 normal tissues, 28 nodular
      hyperplasias, 38 papillary thyroid carcinomas (PTCs) and 11 poorly differentiated
      thyroid carcinomas (PDTCs). By real-time RT-PCR, we observed that tumours
      negative for the PAX8-PPARgamma rearrangement expressed lower levels of PPARgamma
      mRNA than the NT. Overexpression of PPARgamma transcripts was detected in 80%
      (four of five) of translocation-positive tumours. Diffuse nuclear staining was
      significantly (P<0.05) less prevalent in FTCs (53%; 18 of 34), PTCs (49%; 19 of
      39) and PDTCs (0%; zero of 13) than in normal tissue (77%; 36 of 47). Peroxisome
      proliferator-activated receptorgamma-negative FTCs were more likely to be locally
      invasive, to persist after surgery, to metastasise and to have poorly
      differentiated areas. Papillary thyroid carcinomas with a predominantly
      follicular pattern were more often PPARgamma negative than classic PTCs (80% vs
      28%; P=0.01). Our results demonstrated that PPARgamma is underexpressed in
      translocation-negative thyroid tumours of follicular origin and that a further
      reduction of PPARgamma expression is associated with dedifferentiation at later
      stages of tumour development and progression.

PMID- 15238981
TI  - Interstitial photodynamic therapy as salvage treatment for recurrent head and
      neck cancer.
AB  - Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic
      therapy (PDT) to internal tumours using light delivered via fibres inserted
      percutaneously. This phase I-II study assessed the safety and efficacy of IPDT
      for patients with persistent or recurrent head and neck cancer unsuitable for
      further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last
      hope' salvage treatment. Patients were sensitised with 0.15 mg kg(-1) mTHPC (meso
      tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted
      directly into the target tumour (20 J per site at 652 nm) under image guidance.
      In all, 45 patients were treated. Nine achieved a complete response. Five are
      alive and free of disease 10-60 months later. Symptomatic relief (mainly for
      bleeding, pain or tumour debulking) was achieved in a further 24. The median
      survival (Kaplan-Meier) was 16 months for the 33 responders, but only 2 months
      for the 12 nonresponders. The only serious complication was a carotid blow out 2
      weeks after PDT. No loss of function was detected in nerves encased by treated
      tumours. Interstitial photodynamic therapy provides worthwhile palliation with
      few complications and occasional long-term survivors for otherwise untreatable
      advanced head and neck cancers. It is a treatment option worth adding to those
      available to integrated head and neck oncology teams.

PMID- 15238982
TI  - Breast cancer with different prognostic characteristics developing in Danish
      women using hormone replacement therapy.
AB  - The aim of this study is to investigate the risk of developing prognostic
      different types of breast cancer in women using hormone replacement therapy
      (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993.
      Incident breast cancer cases and histopathological information were retrieved
      through the National Danish registries. The follow-up ended on 31 December 1999.
      Breast cancer developed in 244 women, of whom 172 were invasive ductal
      carcinomas. Compared to never users, current users of HRT had an increased risk
      of a hormone receptor-positive breast cancer, but a neutral risk of receptor
      negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI):
      2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for
      difference=0.013). The risk of being diagnosed with low histological malignancy
      grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and
      RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with
      other prognostic characteristics, the risk was increased equally for the
      favourable and non favourable types. Current users of HRT experience a two- to
      four-fold increased risk of breast cancer with various prognostic
      characteristics, both the favourable and non favourable types. For receptor
      status, the risk with HRT was statistically significantly higher for hormone
      receptor-positive breast cancer compared to receptor-negative breast cancer.

PMID- 15238983
TI  - Patient, carer and health service outcomes of nurse-led early discharge after
      breast cancer surgery: a randomised controlled trial.
AB  - Patients with breast cancer who require axillary clearance traditionally remain
      in hospital until their wound drains are removed. Early discharge has been shown
      to improve clinical outcomes, but there has been little assessment of the
      psychosocial and financial impact of early discharge on patients, carers and the
      health service. This study aimed to evaluate the effectiveness of a nurse-led
      model of early discharge from hospital. Main outcome measures were quality of
      life and carer burden. Secondary outcomes included patient satisfaction, arm
      morbidity, impact on community nurses, health service costs, surgical
      cancellations and in-patient nursing dependency. A total of 108 patients
      undergoing axillary clearance with mastectomy or wide local excision for breast
      cancer were randomised to nurse-led early discharge or conventional stay. Nurse
      led early discharge had no adverse effects on quality of life or patient
      satisfaction, had little effect on carer burden, improved communication between
      primary and secondary care, reduced cancellations and was safely implemented in a
      mixed rural/urban setting. In total, 40% of eligible patients agreed to take
      part. Nonparticipants were significantly older, more likely to live alone and had
      lower emotional well being before surgery. This study provides further evidence
      of the benefits of early discharge from hospital following axillary clearance for
      breast cancer. However, if given the choice, most patients prefer to stay in
      hospital until their wound drains are removed.

PMID- 15238984
TI  - A phase II feasibility study of carboplatin followed by sequential weekly
      paclitaxel and gemcitabine as first-line treatment for ovarian cancer.
AB  - A total of 53 women with chemotherapy-naive stage Ic-IV ovarian cancer were
      treated with four cycles of carboplatin area under the curve 7 every 3 weeks,
      followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and
      gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had
      stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%)
      completed all planned treatment; 27 of the 32 (84%) patients with radiologically
      evaluable disease had partial or complete responses; and 30 of the 39 patients
      (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this
      value. At a median follow-up of 28 months, 31 patients had relapsed with a median
      progression-free survival of 19.5 months. In total, 79% of patients were alive at
      2 years. Common Toxicity Criteria grade 3/4 haematological toxicity,
      predominantly neutropenia, was seen in 57% of the patients. A certain degree of
      pulmonary toxicity was observed; eight patients had symptomatic breathlessness,
      +/- decreased diffusing capacity of the lung for carbon monoxide, and
      interstitial chest X-ray changes during the weekly phase. In all cases, this
      toxicity was reversible. No significant neurotoxicity was seen. This regimen is
      generally well tolerated with encouraging efficacy. However, the observation of
      pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine
      regimen, was of some concern. Alternative schedules, including 3-weekly taxanes,
      are currently being evaluated.

PMID- 15238985
TI  - A novel polymorphism in the 1A promoter region of the vitamin D receptor is
      associated with altered susceptibilty and prognosis in malignant melanoma.
AB  - The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of
      the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as
      predicted by tumour (Breslow) thickness, has been reported previously. We now
      report a novel adenine-guanine substitution -1012 bp relative to the exon 1a
      transcription start site (A-1012G), found following screening by single-stranded
      conformational polymorphism of this promoter region. There was a total of 191 MM
      cases, which were stratified according to conventional Breslow thickness groups,
      cases being randomly selected from each group to form a distribution
      corresponding to the known distribution of Breslow thickness in our area, and
      this population (n=176) was compared to 80 controls. The A allele was over
      represented in MM patients and, with GG as reference, odds ratio (OR) for AG was
      2.5, 95% confidence interval (CI) 1.1-5.7, (P=0.03) and AA 3.3, CI 1.4-8.1,
      (P=0.007). The outcome was known in 171 of 191 patients and the A allele was
      related to the development of metastasis, the Kaplan-Meier estimates of the
      probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4-16%; AA 21%, CI 12
      36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on
      metastasis was independent of tumour thickness and A-1012G may have predictive
      potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants
      (f and t) were significantly related to the development of metastasis, although
      there was a strong relationship of fftt with the thickest Breslow thickness group
      (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms
      (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A
      1012G polymorphism on metastasis, the probability of metastasis for AAff at 5
      years follow-up being 57%, CI 24-92%.

PMID- 15238986
TI  - Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of
      patients with advanced non-small-cell lung cancer pretreated with docetaxel and
      cisplatin: a multicentre, randomised, phase II study.
AB  - To compare irinotecan (CPT-11)+gemcitabine vs CPT-11 alone as second-line
      treatment for patients with advanced non-small cell lung cancer (NSCLC)
      progressing after docetaxel-cisplatinum-based therapy. A total of 147 evaluable,
      pretreated patients, with NSCLC, received either gemcitabine (1000 mg m(-2), days
      1 and 8)+CPT-11 (300 mg m(-2), day 8) (Group A, n=76) or CPT-11 (300 mg m(-2),
      day 1) (Group B, n=71), every 3 weeks. All patients were evaluable for response
      and toxicity. The objective response rate was 18.4% (95% CI: 9.71-27.14%) and
      4.2% (95% CI: 0-8.90%) (P=0.009) for groups A and B, respectively. No significant
      differences between the two groups in terms of the median duration of response,
      time to tumour progression, overall survival and 1-year survival were observed.
      The CPT-11/gemcitabine regimen significantly improved the patients' quality of
      life ('general mood today' (P=0.014), 'coughing' (P=0.003) and 'intensity of
      symptoms' (P=0.034)) compared with CPT-11. More cycles had to be delayed
      (P=0.001) and required prophylactic growth factor support (P=0.001) in Group A
      than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed
      febrile neutropenia (P=0.09); one patient died of sepsis in each group. Three
      additional (Group A, n=1; Group B, n=2) treatment-related deaths were observed.
      Grade 3-4 haematologic toxicity was comparable in the two groups except anaemia
      (P=0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and
      similar in the two groups. CPT-11+gemcitabine resulted in a higher response rate
      and better control of disease-related symptoms than CPT-11 alone, but without any
      improvement in the overall survival.

PMID- 15238987
TI  - Fatigue and cancer: causes, prevalence and treatment approaches.
AB  - Fatigue is the most prevalent cancer-related symptom and has a significant
      adverse impact on patients' functional ability and quality of life. Hypotheses
      regarding the aetiology of cancer-related fatigue are discussed, and clinical
      practice guidelines for the evaluation and management of oncology patients with
      fatigue are reviewed. Both nonpharmacologic and pharmacologic strategies for the
      management of fatigue are summarised.

PMID- 15238988
TI  - UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in
      metastatic colorectal cancer.

PMID- 15238990
TI  - Capecitabine in combination with mitomycin C in patients with gastrointestinal
      cancer: results of an extended multicentre phase-I trial.
AB  - The aim of this study was to determine the dose-limiting toxicity (DLT) and
      establish the recommended dose for mitomycin C added every 3 weeks to the
      standard combination dose of capecitabine. Cohorts of at least three patients
      with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2)
      orally twice daily on days 1-14 plus i.v. bolus mitomycin C on day 1 at doses of
      4, 6, 8 or 10 mg m(-2) (corresponding to dose levels I-IV). Cycles were repeated
      every 3 weeks. Two treatment cycles were considered for the evaluation of DLTs.
      Of the 53 patients enrolled, the majority had colorectal (n=27) or gastric (n=14)
      cancers. Patients had received a median of two lines of prior chemotherapy (34%
      with >/=3 lines and 87% with prior 5-FU-based therapy). At the recommended dose
      level (IV, n=30), grade 3 adverse events during cycles 1 and 2 were: anaemia
      (10%); leukopenia (3%); thrombocytopenia (3%); stomatitis/mucositis (3%); hand
      foot syndrome (3%). Two patients experienced DLTs (mucositis, n=1; neutropenic
      fever, n=1), but there were no grade 4 events. The median dose intensity for
      capecitabine and mitomycin C was 100% during cycles 1 and 2 and only four
      patients required postponement of therapy. Of the 43 patients evaluable for
      efficacy, seven achieved partial and minor remissions (16%; 95% CI, 5-28%), and
      12 patients (28%) had stable disease. The favourable safety profile and promising
      activity of the capecitabine/mitomycin C combination, even in heavily pretreated
      patients, warrant further evaluation in patients with advanced colorectal and
      gastric cancers.

PMID- 15238991
TI  - Behavioral alterations in rats prenatally exposed to valproic acid: animal model
      of autism.
AB  - Autism is a severe behavioral disorder characterized by pervasive impairments in
      social interactions, deficits in verbal and nonverbal communication, and
      stereotyped, repetitive patterns of behaviors and interests. Recently, a new
      rodent model of autism was created by exposure of rat fetuses to valproic acid
      (VPA) on the 12.5th day of gestation (VPA rats). The model has striking
      anatomical, pathological, and etiological similarities to human data; however, it
      has not been characterized behaviorally. In order to determine if VPA rats
      present behavioral aberrations observed in autism, their behavior was extensively
      evaluated in a battery of tests. The results of the present experiments
      demonstrate that VPA rats exhibit: (1) lower sensitivity to pain and higher
      sensitivity to nonpainful stimuli, (2) diminished acoustic prepulse inhibition,
      (3) locomotor and repetitive/stereotypic-like hyperactivity combined with lower
      exploratory activity, and (4) decreased number of social behaviors and increased
      latency to social behaviors. In addition, VPA rats showed delayed maturation,
      lower body weight, delayed motor development, and attenuated integration of a
      coordinated series of reflexes, delayed nest-seeking response mediated by
      olfactory system, and normal negative geotaxis. Interestingly, all behavioral
      aberrations described in this paper appear before puberty, which could
      distinguish the VPA rat model of autism from other animal models of
      neurodevelopmental disorders, especially rodent models of schizophrenia. Our
      results bring further support to validity of the proposed VPA animal model of
      autism, suggesting similarities between the observed pattern of behavioral
      alterations in VPA rats and features of disturbed behavior in autistic patients.

PMID- 15238992
TI  - Dichotic listening tests of functional brain asymmetry predict response to
      fluoxetine in depressed women and men.
AB  - Patients having a depressive disorder vary widely in their therapeutic
      responsiveness to a selective serotonin reuptake inhibitor (SSRI), but there are
      no clinical predictors of treatment outcome. Studies using dichotic listening,
      electrophysiologic and neuroimaging measures suggest that pretreatment
      differences among depressed patients in functional brain asymmetry are related to
      responsiveness to antidepressants. Two new studies replicate differences in
      dichotic listening asymmetry between fluoxetine responders and nonresponders, and
      demonstrate the importance of gender in this context. Right-handed outpatients
      who met DSM-IV criteria for major depression, dysthymia, or depression not
      otherwise specified were tested on dichotic fused-words and complex tones tests
      before completing 12 weeks of fluoxetine treatment. Perceptual asymmetry (PA)
      scores were compared for 75 patients (38 women) who responded to treatment and 39
      patients (14 women) who were nonresponders. Normative data were also obtained for
      101 healthy adults (61 women). Patients who responded to fluoxetine differed from
      nonresponders and healthy adults in favoring left- over right-hemisphere
      processing of dichotic stimuli, and this difference was dependent on gender and
      test. Heightened left-hemisphere advantage for dichotic words in responders was
      present among women but not men, whereas reduced right-hemisphere advantage for
      dichotic tones in responders was present among men but not women. Pretreatment PA
      was also predictive of change in depression severity following treatment.
      Responder vs nonresponder differences for verbal dichotic listening in women and
      nonverbal dichotic listening in men are discussed in terms of differences in
      cognitive function, hemispheric organization, and neurotransmitter function.

PMID- 15238993
TI  - Transdermal absorption of (-)-linalool induces autonomic deactivation but has no
      impact on ratings of well-being in humans.
AB  - Essential lavender oil has a long tradition as a mild sedative in herbal
      medicine. Relaxing effects after inhalation have also been demonstrated for one
      of its main constituents, (-)-linalool. The aim of the present investigation was
      to determine the effects of this monoterpenoid alcohol on human physiological
      parameters (blood oxygen saturation, breathing rate, eye-blink rate, pulse rate,
      skin conductance, skin temperature, surface electromyogram as well as systolic
      and diastolic blood pressure) and assessments of subjective well-being. (-)
      Linalool was applied to 14 healthy subjects by percutaneous administration.
      Inhalation of the fragrance was prevented by means of breathing masks. (-)
      Linalool induced deactivation with respect to physiology, that is, a decrease of
      systolic blood pressure and a smaller decrease of skin temperature, compared to a
      corresponding control group receiving a placebo, but had no effects on subjective
      evaluation of well-being.

PMID- 15238994
TI  - Expression of the CS- and US-pre-exposure effects in the conditioned taste
      aversion paradigm and their abolition following systemic amphetamine treatment in
      C57BL6/J mice.
AB  - In classical conditioning, pre-exposures to either the to-be-conditioned stimulus
      (CS) or unconditioned stimulus (US) can retard subsequent conditioning between
      the CS and US. The present experiment evaluated the expression of these two pre
      exposure effects in mice of the C57BL6/J strain, one of the most common
      background strains for genetically altered mice. We tested whether their
      expression would be disrupted by amphetamine treatment (2.5 mg/kg, i.p.) in a
      conditioned taste aversion paradigm with sucrose as the CS and lithium chloride
      induced gastric malaise as the US. We found that one pre-exposure (PE) to either
      the CS or the US reduced aversion to sucrose solution in the controls following
      conditioning, but no such tendency was evident in the amphetamine-treated mice.
      The present study represents the first report of amphetamine-induced disruption
      of the CS-PE effect (ie latent inhibition) in mice, and the first attempt to
      compare it directly with the US-PE effect in any species. It extended previous
      reports in rats and humans, suggesting that the sensitivity of latent inhibition
      to amphetamine is largely comparable across species, thereby lending credence to
      the use of the latent inhibition effect as a behavioral assay for psychotic-like
      phenotype in transgenic mice. The parallel observation in the US-PE effect
      further indicates that its expression, at least in the present conditioned taste
      aversion paradigm, may also be under similar influence of the dopaminergic
      system.

PMID- 15238995
TI  - Age-dependent reductions in the level of glial fibrillary acidic protein in the
      prefrontal cortex in major depression.
AB  - The density of glial cells is reduced in certain layers of the dorsolateral
      prefrontal cortex in major depressive disorder (MDD). Moreover, there are
      reductions in the packing density of glial fibrillary acidic protein (GFAP)
      immunoreactive astrocytes in the same cortical layers in younger subjects with
      MDD. The objective of the present study was to test if the level of GFAP is
      preferentially decreased in younger subjects with MDD, and whether GFAP levels
      are correlated with the age of onset of depression. Post-mortem brain tissue
      punches from dorsolateral prefrontal cortex were collected from 15 subjects with
      MDD and 15 age-matched psychiatrically normal control subjects. Western blots
      were performed on gels containing duplicated samples from both subjects of each
      matched pair, and on gels containing samples at different ages from either the
      MDD or the control group. The GFAP level was calculated as the ratio of the
      optical density of GFAP bands to actin bands in subjects with MDD and
      nonpsychiatric controls. Levels of GFAP were significantly lower in subjects with
      MDD as compared to controls and this decrease was most prominent in subjects less
      than 60 years old at the time of death. In the MDD group, GFAP levels were
      positively correlated with age at the time of death and show a trend toward
      correlation with the age of onset of depression. These findings indicate that a
      decrease in levels of GFAP may contribute to the pathophysiology of MDD,
      particularly in subjects of relatively young age.

PMID- 15238996
TI  - Adenovirus-based vascular endothelial growth factor gene delivery to human
      pancreatic islets.
AB  - Islet transplantation is limited by islet graft failure due to poor
      revascularization, host immune rejection and nonspecific inflammatory response.
      Delivery of human vascular endothelial growth factor (hVEGF) gene to the islets
      is likely to promote islet revascularization and survival. We used a bicistronic
      adenoviral vector encoding hVEGF and CpG-free allele of green fluorescent protein
      (Adv-GFP-hVEGF) and introduced into human pancreatic islets by transfection. We
      found that transfection efficiency and apoptosis were dependent on the
      multiplicity of infection (MOI). Compared to Adv-GFP transfected and
      nontransfected islets, the levels of hVEGF secreted from Adv-GFP-hVEGF
      transfected islets were higher and exhibit a linear relationship between hVEGF
      expression and MOI (10-5000). Persistent, but low level expression of hVEGF from
      nontransfected islets was also observed. This may be due to expression of the
      endogenous hVEGF gene under hypoxic conditions. The levels of DNA fragmentation
      determined by ELISA of islet lysates were dependent on the MOI of Adv-GFP-hVEGF.
      On glucose challenge, insulin release from transfected islets was comparable to
      nontransfected islets. Immunohistochemical staining for hVEGF was very high in
      Adv-GFP-hVEGF transfected islets. Weak staining was also observed for hCD31 in
      both transfected and nontransfected islets. These findings suggest that Adv-GFP
      hVEGF is a potential candidate for promoting islet revascularization.

PMID- 15238997
TI  - An inhibit (INH) molecular logic gate based on 1,8-naphthalimide-sensitised
      europium luminescence.
AB  - A novel molecular logic gate with inhibit (INH) function has been developed,
      based on oxygen and a threshold europium concentration as input information and
      long-lived red europium luminescence as output signal.

PMID- 15238998
TI  - Variation of the enhanced biologically damaging solar UV due to clouds.
AB  - The variation of the biologically damaging solar UV (UVBE) enhanced by clouds
      above that of clear sky UVBE has been investigated. This was undertaken for
      summer through to winter for SZA of 5 to 60 degrees employing an integrated
      automatic cloud and spectral UV measurement system that recorded the solar UV
      spectra and the sky images at five minute intervals. The UVBE calculated with
      action spectra with higher relative effectiveness in the UVA produced the lower
      percentage of cloud enhanced cases. The DNA UVBE provided the highest percentage
      of cloud enhanced cases compared to the total number of UV scans with 2.2% cloud
      enhanced cases. As a comparison, the plant and fish melanoma UVBE provided the
      lowest percentage of cloud enhanced cases with 0.6 to 0.8% cloud enhanced cases.
      For the cases of cloud enhanced UVBE, the average ratio of the measured UVBE to
      calculated cloud free UVBE for the photokeratitis, cataracts, plant, generalized
      plant damage and fish melanoma action spectra was 1.21 to 1.25. In comparison,
      the highest value of 1.4 was for the DNA action spectrum.

PMID- 15239000
TI  - A comparative analysis of phenothiazinium salts for the photosensitisation of
      murine fibrosarcoma (RIF-1) cells in vitro.
AB  - Photodynamic therapy (PDT) is a treatment combining a photosensitiser, molecular
      oxygen and visible light of characteristic wavelength to produce cytotoxic
      reactive oxygen species (ROS). Within our centre, a series of phenothiazinium
      salts were synthesised and initial characterisation studies performed to
      determine any potential use for PDT. All photosensitisers within the series were
      shown to have useful spectral properties for PDT, with absorbance lambdamax above
      667 nm. The Log P values of the compounds were shown to range from -0.9 to >
      +2.0. Furthermore, Log P values were shown to be important in determining the
      site of subcellular localisation and as such the site of photooxidative damage.
      Derivatives with a Log P value of greater than +1.0 were shown to initially
      localise to the lysosomes then relocalise throughout the cytoplasm following
      illumination, whereas compounds with intermediate Log P values (-0.7 to +1.0) all
      remained lysosomal. Only methylene blue (Log P-0.9) was shown to redistribute to
      the nucleus upon illumination. Following treatment of RIF-1 cells with each
      phenothiazinium salt for 1 h and subsequent exposure to 665 nm laser light at a
      fluence rate of 10 mW cm(-2)(18 J cm(-2)), it was determined that the most potent
      photosensitiser was 260-fold more potent than methylene blue. Furthermore, the
      PDT efficacy of the photosensitisers was shown to be related to the level of
      mitochondrial damage induced directly following illumination.

PMID- 15238999
TI  - The effects of manganese doping on UVA absorption and free radical generation of
      micronised titanium dioxide and its consequences for the photostability of UVA
      absorbing organic sunscreen components.
AB  - The effect of manganese doping on the free radical generation rate, free radical
      scavenging and UVA absorption properties of micronised sunscreen grade titania
      has been studied with respect to enhancement of the UVA photostability of test
      sunscreen formulations containing the organic UVA absorber Parsol 1789. Manganese
      doping has been shown to increase the UVA:UVB absorption ratio of titania, reduce
      free radical generation rates by over 90%, and provide free radical scavenging
      behaviour. Adding manganese-doped titania to a test formulation incorporating
      Parsol 1789 shows that manganese doping increases UVA attenuation stability by up
      to 3 times the amount achieved by comparable commercial undoped titania
      materials. HPLC data shows this to be related to an improved stabilisation of the
      organic sunscreen components. Manganese doped titania shows improved efficacy
      over undoped titania in sunscreen formulations containing organic UV absorbers.

PMID- 15239001
TI  - Positional effects of the hydroxy substituent on the photochemical and
      photophysical behavior of 3- and 4-hydroxystilbene.
AB  - The photophysical and photochemical behavior of meta- and para-hydroxy- and
      methoxystilbene are reported and compared to the aminostilbenes. Absorption
      spectra of all four studied compounds in organic solution display a featureless,
      intense long-wavelength absorption band around 300 nm. In basic aqueous solution,
      meta-hydroxystilbene displays a less intense band with a long-wavelength
      shoulder, a consequence of configuration interaction from the O(-) substituent.
      Emission from the meta-substituted stilbenes is much stronger than from the para
      isomers, with an especially large effect for the hydroxystilbenes in solvents
      that are good hydrogen bond acceptors. Emission from the hydroxystilbenes is weak
      in aqueous solution, and even weaker in basic solution, a consequence of facile
      nonradiative decay. The excited state lifetimes of the meta isomers are longer
      than those with para substituents. Ground and excited state acidity constants are
      reported for the hydroxystilbenes. In the ground state, the para derivative is an
      order of magnitude more acidic than the meta isomer, however, its short excited
      state lifetime precludes excited state deprotonation. In contrast, 3
      hydroxystilbene does exhibit deprotonation in its excited state.

PMID- 15239002
TI  - Photophysics and photochemistry of water-soluble, sitting-atop bis-thallium(I)
      5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin.
AB  - In aqueous solutions, thallium(I) ions and 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrin form a kinetically labile metalloporphyrin of 2 : 1
      composition (Tl(2)P(4-)). The formation constant of this sitting-atop (SAT)
      complex is relatively low (beta2/[H+]2= 3.55 x 10(3) M(-2) at pH = 7), due to the
      large size and rather small charge of Tl+. As a consequence of the considerably
      weak metal-ligand interaction in this system, the 1 : 1 species does not appear
      in detectable concentration. Both the absorption and the emission properties of
      the Tl(2)P(4-) complex are characteristic for the typical SAT metalloporphyrins.
      Compared to the corresponding values of the free-base porphyrin, the diminished
      fluorescence quantum efficiency (Qfl= 0.0131 vs. 0.056) of Tl(2)P(4-) can be
      accounted for by the heavy-atom effect, while the larger Stokes shift (442 vs.
      282 cm(-1)) indicates a stronger distortion of the ligand plane. Both Soret- and
      Q-band irradiations of the Tl(2)P(4-) complex lead to the degradation of the
      porphyrin with quantum yields of magnitude 3 x 10(-4). The primary photochemical
      step in this process is ligand-to-metal charge transfer reaction, which is
      unusual for normal (coplanar) metalloporphyrins. In the case of SAT complexes,
      the kinetic lability facilitates the separation of the primary redox products,
      followed by an irreversible ring-opening of the oxidized porphyrin. Photoinduced
      electron ejection as a considerable step in the degradation mechanism could be
      ruled out.

PMID- 15239003
TI  - Rose Bengal adsorbed on microgranular cellulose: evidence on fluorescent dimers.
AB  - Rose Bengal adsorbed on microgranular cellulose was studied in the solid phase by
      total and diffuse reflectance and steady-state emission spectroscopy. A simple
      monomer-dimer equilibrium fitted reflectance data up to dye loadings of 4 x 10(
      7) mol (g cellulose)(-1) and allowed calculation of monomer and dimer spectra.
      Further increase of dye loading resulted in the formation of higher aggregates.
      Observed emission and excitation spectra and quantum yields were corrected for
      reabsorption and reemission of luminescence, using a previously developed model,
      within the assumption that only monomers are luminescent [M. G. Lagorio, L. E.
      Dicelio, M. I. Litter and E. San Roman, J. Chem. Soc., Faraday Trans., 1998, 94,
      419]. An apparent increase of fluorescence quantum yield with dye loading was
      found, which was attributed to the occurrence of dimer fluorescence. Extension of
      the model to two luminescent species (i.e. monomer and dimer) yielded constant
      fluorescence quantum yields for the monomer, phiM= 0.120 +/- 0.004, and for the
      dimer, phiD= 0.070 +/- 0.006. The monomer quantum yield is close to the value
      found for the same dye in basic ethanol. The presence of fluorescent dimers and
      calculated quantum yields are supported by analysis of the excitation spectra and
      other experimental evidence. The possible occurrence of non-radiative energy
      transfer and the effect of surface charge on the properties of the dimer are
      analyzed.

PMID- 15239004
TI  - Lactic acid production with lactate dehydrogenase using the visible light
      sensitization of zinc porphyrin.
AB  - Lactic acid production with L-lactate dehydrogenase from Pig heart (LDH) and
      reduced methyl viologen produced by the visible light photosensitization of zinc
      tetrakis(4-methylpyridyl)porphyrin (ZnTMPyP) was investigated. When the sample
      solution containing triethanolamine as an electron-donating reagent, ZnTMPyP,
      methyl viologen as an electron carrier, pyruvic acid and LDH in potassium
      phosphate buffer (pH 7) was irradiated, lactic acid production was observed.
      After 240 min irradiation, the amount of lactic acid production and the yield of
      pyruvic acid to lactic acid were estimated to be 0.17 mmol dm(-3) and 17.0%,
      respectively.

PMID- 15239005
TI  - Biradical to biradical rearrangement via 1,3-H atom transfer in
      photocycloisomerizations of 4-pent-4-enylcyclohex-2-enones.
AB  - An unprecedented 'carbonyl-O-assisted' 1,3-H atom transfer from a CH2 group to a
      primary alkyl radical center in 1,4-biradicals, formed in a crossed addition mode
      in the photocycloisomerization of 4-pent-4-enylcyclohex-2-enones, is discussed.

PMID- 15239006
TI  - Photocyclization of trans-1-(1'-naphthyl)-2-(3-hydroxyphenyl)ethene: evidence for
      adiabatic 1trans*-->1cis* photoisomerization.
AB  - The photochemistry of trans- and cis-1-(1'-naphthyl)-2-(3-hydroxyphenyl)ethene in
      cyclohexane and acetonitrile was examined. In cyclohexane fluorescence is the
      main deactivation channel for the 1trans* isomer while photocyclization is the
      main reaction of the 1cis* isomer. The weighty formation of hydroxychrysene
      following one photon absorption by the trans isomer furnished evidence of an
      adiabatic 1trans*-->1cis* isomerization. The photoreactivity data in acetonitrile
      indicated the influence of solvent polarity on the shape of the excited state
      surface.

PMID- 15239007
TI  - Conformer-specific and two-fold adiabatic photoisomerization of ZZ-1,4-di-(2
      quinolylethenyl)benzene.
AB  - Irradiation of the ZZ stereoisomer of 1,4-di-(2'-quinolylethenyl)-benzene was
      found to cause direct adiabatic (one photon-two bond) isomerization to a product
      having the same lifetime as the EE isomer but a rather different spectrum with
      respect to that obtained by direct excitation of the EE one. To clarify this
      unexpected behaviour, the conformational equilibria of the EE stereoisomer have
      been studied in non-polar solvent by fluorimetry. The most abundant conformers,
      formed by the hindered rotation of the condensed-ring groups around the quasi
      single bond with the ethenic carbons, have been characterized by the selective
      effect of the excitation energy on the fluorescence spectrum. The combined
      application of the principal component analysis allowed the separation of the
      spectral properties of three conformers to be achieved. Information on their
      structures was obtained by theoretical calculations. The results of the present
      conformational study clearly indicated that the fluorescence spectrum of the
      photoproduct of ZZ belongs to a specific component of the conformer mixture of
      the EE isomer.

PMID- 15239008
TI  - Photolysis of alpha-xylyl chlorides: an efficient deep-UV photoinitiating system
      for radical and cationic polymerization.
AB  - Photoacid generators (PAG) are chemical systems where light absorption renders
      strong acid formation, typically with quantum yields greater than one. Many
      compounds bearing halogen atoms are reported to produce hydrogen halides upon
      photolysis. Here, alpha-chloroxylene derivatives (ortho, meta and para) were
      subject of a photolysis study in order to: (i) determine the operative mechanism,
      (ii) identify the products formed and (iii) quantify the amount of HCl formed.
      Product structure and quantum yields of HCl formation where determined for the
      photolysis of alpha-chloro-o-xylene (1), alpha-chloro-m-xylene (2), alpha-chloro
      p-xylene (3), alpha, alpha'-dichloro-o-xylene (4), alpha, alpha'-dichloro-m
      xylene (5) and alpha, alpha'-dichloro-p-xylene (6) in apolar (benzene, cumene,
      ethylbenzene, toluene and isooctane) and polar (methanol, n-propanol, isopropyl
      alcohol) solvents. Some of these compounds were analysed by laser flash
      photolysis in argon-purged isooctane as solvent to examine the possible reaction
      intermediates involved. The observed products are derived from typical radical
      reactions like recombination, dimerization and hydrogen abstraction from the
      starting compound or from solvents. The formation of HCl is expected as the
      result of C-Cl homolysis followed by hydrogen abstraction by chlorine atom. The
      results showed yields ranging from 1.2 to 18, depending on the conditions used.
      These numbers indicate the potential use of these compounds as PAG systems for
      the deep UV region.

PMID- 15239009
TI  - Light- and singlet oxygen-mediated antifungal activity of phenylphenalenone
      phytoalexins.
AB  - The light-induced singlet oxygen production and antifungal activity of
      phenylphenalenone phytoalexins isolated from infected banana plants (Musa
      acuminata) are reported. Upon absorption of light energy all studied
      phenylphenalenones sensitise the production of singlet oxygen in polar and non
      polar media. Antifungal activity of these compounds towards Fusarium oxysporum is
      enhanced in the presence of light. These results, together with the correlation
      of IC50 values under illumination with the quantum yield of singlet oxygen
      production and the enhancing effect of D2O on the antifungal activity, suggest
      the intermediacy of singlet oxygen produced by electronic excitation of the
      phenylphenalenone phytoalexins.

PMID- 15239010
TI  - [Prognostic factors in severe head injury].
AB  - The knowledge of the so called prognostic factors or indicators involved in
      severe head injury (SHI) is an issue of great interest to make predictions about
      the future of patients with this pathology. Those indicators constitute the basic
      elements of the different prognostic formulas or models carried out in order to
      make predictions in SHI. The mentioned models, therefore, will be constructed by
      a group of variables (prognostic indicators or factors) and several scales
      (prognostic scales) that are useful for measuring the final outcome of these
      patients. In this paper we resume, after an exhaustive review of the literature,
      the knowledge about the prognostic factors related to SHI. These indicators have
      been classified as follows: clinical, radiological, physiological, and
      biochemical. Moreover, we have briefly described the prognostic scales more
      commonly used in SHI.

PMID- 15239011
TI  - [Endoscopic third ventriculostomy: risk factors for failure and evolution of
      ventricular size].
AB  - INTRODUCTION: Endoscopic third ventriculostomy is the treatment of choice for non
      communicating hydrocephalus at our institution. Several factors have been
      associated with failure of endoscopic third ventriculostomy. The goals of the
      study have been to evaluate the outcome, the influence of factors theoretically
      prone to failure of ventriculostomy and the evolution of ventricular size.
      MATERIAL AND METHODS: Fifty-six patients (mean age 48.5 yrs) treated with an
      endoscopic third ventriculostomy during the period 1997-2002 were analysed
      retrospectively. Hydrocephalus was classified as acute (68%) and chronic forms.
      Etiology was classified in space-occupying lesions (59%), primary aqueductal
      stenosis (34%) and Chiari malformation (7%). The presence of the following
      factors theoretically prone to failure was considered: age below one year,
      history of mielomeningocele, cerebrospinal fluid (CSF) infection, intracranial
      haemorrhage, radiotherapy, craniotomy and previous treatment of hydrocephalus
      with a shunt. Ventricular size was measured linearly with four ventricular index
      pre- and postoperatively. RESULTS: The global success rate was 71.4% (mean follow
      up 26 months). Endoscopic third ventriculostomy for hydrocephalus secondary to
      cerebral metastases obstructing CSF pathways was associated with a higher risk of
      failure (p=0.006). None of the risk factors considered was associated with a
      higher risk of failure. The evolution of the ventricular size measured with
      linear methods is associated with outcome. Evans ratio, third ventricle index,
      cella media index and ventricular score decreased in patients whose outcome is
      satisfactory and increased in those cases deemed clinical failures (p< 0.05).
      CONCLUSION: The risk of failure increases in patients with cerebral metastases
      close to CSF pathways, likely due to the concurrence of mechanisms other than
      obstruction. Changes in ventricular size are associated with outcome.

PMID- 15239012
TI  - [Clinical applications of in vivo proton magnetic resonance spectroscopy in the
      study of astrocytomas: state of the art].
AB  - We review the current state in literature of the use of magnetic resonance
      spectroscopy in the assessment and characterization of cerebral astrocytomas.
      Special attention will be paid to the presurgical grading of astrocytomas and to
      the role of spectroscopy in differentiating these tumors from other neoplastic
      and nonneoplastic brain lesions.

PMID- 15239013
TI  - [Anterior cervical interbody fusion with treathed cylindrical bone versus bak
      cace: a comparative study].
AB  - The authors conducted a prospective and randomized study in 44 consecutive
      patients requiring cervical interbody fusion following anterior cervical
      discectomy to compare the efficacy of heterologous threaded cylindrical bone
      (Unilab Surgibone) versus titanium implant (Bak-C; Spine-Tech, Minneapolis ). The
      patients were evaluated between two and five years postoperatively and the
      objectives of the study were to assess the potential differences in implant
      shifting, interespace collapse, angulation, maintenance of cervical alignment and
      lordosis, and clinical and radiographic fusion success rates between the two
      fusion substrates. Clinical results were satisfactory with both types of implant.
      However the threaded cylindrical titanium implant was found to be superior to the
      heterologous threaded cylindrical bone as an interbody substrate after single 
      and multiple- level anterior cervical decompression procedures with respect to
      maintenance of cervical interspace height, interspace angulation and radiographic
      fusion success rates.

PMID- 15239014
TI  - [Intraabdominal complications in the lumbar disc surgery].
AB  - INTRODUCTION: : Removal of a lumbar disc herniation is, at present, the most
      frequent surgical procedure, related to the spine in Neurosurgical Departments.
      It carries a very low rates of complications and a short postoperative hospital
      stay. However, in spite of their rarity, serious adverse intraoperative
      complications may occur, so we must be aware of its existence in order to make an
      early diagnosis and treatment to prevent a fatal outcome. It is important to
      ensure that the patient understand the possible complications and obtaining
      written consent to avoid later medico-legal problems. CLINICAL CASES: We report
      two cases with typical lumbociatic pain secondary to lumbar disc herniation
      operated at our Department, that resulted in intraoperative complications, due to
      perforation of intraabdominal structures. Initially, the patients underwent
      planned flavectomy, followed by simple disc removal. However, symptoms of
      abdominal pain and systemic hypotension in each case, began some hours later.
      Early diagnosis was achieved using abdominal-pelvic CT scan, showing an
      intestinal perforation in one patient and a tear of both iliac artery and vein in
      the other. In both, an urgent laparotomy was performed by colleagues from the
      Department of General and Vascular Surgery, with surgical repair. The final
      outcome was good and both are asymptomatic. CONCLUSION: Surgical removal of the
      lumbar disc herniation is a very effective procedure, but is not free from
      certain severe though rare complications. Intestinal perforation and vascular
      tears are two possible complications to suspect if abdominal pain or systemic
      arterial to suspect if abdominal pain or systemic arterial urgent surgical repair
      of such complications. It is of vital importance that the patient knows the
      existence of such complications and so obtain a written consent.

PMID- 15239015
TI  - [Medulloblastoma presenting as an extra-axial tumor in the cerebellopontine
      angle].
AB  - Differences in the imaging characteristic of adult medulloblastomas have been
      reported, including involvement of lateral cerebellar hemispheres with an extra
      axial appearance. We present a case report of this rare circumstance: a 40 year
      old man presented with a 3 weeks history of headache, morning vomiting and left
      hearing difficulties. Magnetic resonance imaging revealed a left cerebellopontine
      angle (CPA) tumor, like a well circumscribed homogeneously enhancing mass.
      Through a left suboccipital craniectomy the tumor was totally removed. It
      presented as a cerebellopontine angle tumor, like a meningioma, and not as an
      intra-axial tumor. Histological analysis revealed that the tumor was composed of
      densely packed with highly proliferative cells that produce a dense intercellular
      reticulin fiber network. Inmunohistochemical analysis showed positive expression
      to synaptophysin, specific neuronal enolase and cromogranin. Histological
      diagnosis was crucial to define it as a desmoplastic medulloblastoma the present
      case and to perform postoperative adjuvant therapy. Neurosurgeons should be aware
      of the possibility that a CPA tumor is of intraaxial origin, because this
      increase the variability on pathological diagnosis.

PMID- 15239016
TI  - Cystic mature teratoma of the filum terminale in an adult. Case report and review
      of the literature.
AB  - Intradural spinal teratoma is a very rare entity, more prevalent in childhood,
      that may associate with dysraphic defects. The authors report a 46 years old man
      with a cauda equina syndrome and an L1-2 tumor. An L1-2 laminectomy was performed
      and a mass was resected at the base of the filum terminale, which was in contact
      with the conus medullaris. Histopathological diagnosis was of cystic mature
      teratoma. Spinal teratomas may be found anywhere along the spine, but are more
      frequent in the cauda equina. We discuss the origin of these tumors and review
      the literature concerning these lesions.

PMID- 15239018
TI  - [A story: thirty years of gratitude].

PMID- 15239017
TI  - [Voluminous hypothalamic hamartoma in a 5-month-old boy: Epilepsy and surgery].
AB  - The authors report the case of 5-month-old boy with a hypothalamic hamartoma and
      persistent gelastic seizures in spite of a wide combination of different
      antiepileptic drugs. It was decided to carry out only partial removal of the
      tumor for decompression and to decreasing the activity of the epileptogenic
      focus. Surgical therapy revealed as a valid option in the treatment of the
      uncontrollable gelastic seizures.

PMID- 15239019
TI  - Congenital adrenal hyperplasia - how to improve the transition from adolescence
      to adult life.
AB  - Congenital adrenal hyperplasia (CAH) is caused by a defect in the biosynthesis of
      cortisol that results in maximal activity of the hypothalamic-pituitary adrenal
      axis with hyperplasia of the adrenals and hyperandrogenism due to the
      accumulation of androgen precursors. In the salt-wasting subtype of the disorder,
      which accounts for appr. 75 % of patients with classical CAH, patients are unable
      to synthesise sufficient amounts of aldosterone and are prone to life-threatening
      salt-losing crises, whereas the simple virilising form is predominantly
      characterized by clitoris hypertrophy and posterior labial fusion. In addition, a
      non-classical variant can be discerned which in most cases is diagnosed at the
      time of puberty or early adolescence when hirsutism and menstrual irregularities
      may occur. The vast majority of CAH patients have 21-hydroxylase deficiency (90 -
      95 %). Less common forms, such as 11beta-hydroxylase deficiency, will not be
      discussed in this review. Unfortunately, a considerable number of CAH patients is
      lost to regular and competent follow-up once they move out of paediatric care.
      This is most probably the result of insufficient co-operation between paediatric
      and adult endocrinologists at the time of transition from adolescence to
      adulthood. Furthermore, there is a lack of clinical guidance regarding
      psychosexual development in these patients. In this overview we will focus on
      special aspects of CAH treatment in adolescence and adulthood, and report on our
      10-year experience with a transfer system for endocrine patients from paediatric
      to internal medical care, known as the "Kieler Modell". For practical purposes,
      we here provide charts for follow-up of CAH patients that can be adapted for use
      in any endocrine outpatient clinic.

PMID- 15239020
TI  - Fluid shear of low magnitude increases growth and expression of TGFbeta1 and
      adhesion molecules in human bone cells in vitro.
AB  - Deformation of the bone matrix by mechanical strain causes fluid shifts within
      the osteocytic canaliculi which affect osteocytic cell metabolism. We applied low
      fluid shear (1 - 63 micro Pa for 10 - 48 h) to human osteoblastic cells (HOB) in
      vitro to study its impact on cell proliferation and differentiated functions.
      Proteins involved in translating the physical force into a cellular response were
      characterised. Low fluid shear stress stimulated proliferation of HOB 1.2-fold
      when stress was applied intermittently for 24 h. Shear stress also increased
      differentiated cellular properties such as alkaline phosphatase (ALP) activity
      (121 % of control), fibronectin (FN) and fibronectin receptor (FNR) expression
      (290 % and 200 %, respectively). Prostaglandin E (2) (PGE (2)) and TGFbeta1
      release into the medium were significantly stimulated when shear stress was
      applied for 6 - 12 h and 24 - 48 h, respectively. TGFbeta1 + 2 neutralising
      antibodies or the presence of indomethacine inhibited the mitogenic effect of
      fluid shear and reduced ALP activity to its control level. Furthermore, TGFbeta
      treatment induced a dose-dependent increase in FN and FNR expression. Therefore,
      fluid shear stress of low magnitude (a) suffices to affect HOB metabolism and (b)
      regulates anchorage of HOB via FN and FNR by stimulating osteoblastic PGE (2) and
      TGFbeta secretion.

PMID- 15239021
TI  - Functional parameters before and after parathyroidectomy: a prospective,
      randomized long-term trial on different rat strains.
AB  - For clinical controls before and after parathyroidectomy and for evaluation of
      the function of transplants of parathyroid tissue, it is necessary to establish
      standard values of relevant laboratory parameters for donor and recipient animals
      as well as for different types of nutrition. Since no such data are yet
      available, it was the purpose to define such standards. In a prospective
      randomized trial on 400 rats of the Dark Agouti (DA) and Lewis strain, different
      functional laboratory parameters such as total calcium, intact parathyroid
      hormone, phosphate, 1.25-dihydroxyvitamin D, and alkaline phosphatase were
      measured under a standard and low calcium diet over a period of 40 weeks. Two
      hundred of these animals underwent a parathyroidectomy four weeks after the
      beginning of the study and specimens were evaluated histologically. For all eight
      different study groups normal values could be defined within tight limits for
      parameters which describe the function of the parathyroid gland or elements of
      calcium metabolism under different conditions. The optimal conditions for a
      transplantation model of parathyroid glands were established. Lewis-rats were
      identified as the ideal donor and DA rats as the better recipient animals. These
      data can serve as reference values for future studies on transplantation of the
      parathyroid without immunosuppression.

PMID- 15239022
TI  - Thyroid hormone indices during illness in six hypothyroid subjects rendered
      euthyroid with levothyroxine therapy.
AB  - PURPOSE: We wanted to evaluate changes in the natural course of serum thyroxine
      (T4), tri-iodothyronine (T3), reverse tri-iodothyronine (rT3), and thyroid
      stimulating hormone (TSH) concentrations during hospitalization for an acute
      illness, in subjects rendered euthyroid with Levothyroxine (LT4) replacement
      therapy. METHODS: Six male subjects ranging in age 30 - 65 years with a history
      of primary hypothyroidism were included. They were euthyroid prior to
      hospitalization. LT4 continued to be administered orally in the same pre
      admission daily dose. Serum, T4, T3, rT3, and TSH concentrations were determined
      on day of admission to the intensive care unit (ICU) for an acute illness. These
      were repeated during the first week on alternate days and again during a follow
      up visit 1 week after discharge. Student's t-test, analysis of variance, and
      linear regression were used to analyze the data. RESULTS: Serum T4, T3 declined
      to a nadir and serum rT3 rose to its peak by day 3 of hospitalization before
      returning to pre admission euthyroid levels. Serum TSH declined initially but
      rose to supernormal levels on day 7 before normalization. Significant
      correlations were noted between TSH on one hand and T3/T4 (r = 0.76, p < 0.001)
      and rT3/T4 (r= - 0.64, p < 0.001) ratios. CONCLUSIONS: Alterations ensuing during
      a short stay in the hospital due to an acute illness in subjects with primary
      hypothyroidism rendered euthyroid with appropriate replacement therapy with
      Levothyroxine (LT4) are almost identical to those in normal subjects. These
      changes are probably secondary to altered thyroid hormone metabolism. The altered
      levels of thyroid hormones and TSH noted in these subjects are transient and
      therefore providers should refrain from initiating frequent changes in daily LT4
      replacement dose during the acute illness in these subjects.

PMID- 15239023
TI  - Low grade inflammation in juvenile obesity and type 1 diabetes associated with
      early signs of atherosclerosis.
AB  - BACKGROUND: Subclinical inflammation has been implicated in the initiation and/or
      progression of atherosclerosis. Diabetes mellitus and obesity are risk factors
      for atherosclerosis, and asymptomatic low grade inflammation occurs prior to
      overt vascular lesions in these patients. In contrast to adults, little
      information exists concerning low grade inflammation in young type 1 diabetes and
      juvenile obesity. AIM: To investigate low grade inflammation and immune
      activation in juvenile diabetes mellitus and obesity. METHODS: hs-CRP, soluble
      interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic
      acid, leptin, and homocysteine were determined in 148 patients with juvenile type
      1 diabetes, 86 obese children and 142 normal weighted age-matched healthy
      controls. Intima-media thickness (IMT) and lumen diameter of both common carotid
      arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls,
      10 diabetics, and 34 obese juveniles. RESULTS: Serum hs-CRP was significantly
      elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p <
      0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and
      the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs.
      Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid
      did not differ from the controls. The elevation of hs-CRP was more pronounced in
      obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values
      correlated significantly with body mass index standard deviation score (BMI-SDS)
      values. Furthermore, the IMT and the luminal diameter of CCAs showed significant
      correlations with BMI-SDS values. CONCLUSION: A low grade inflammation as
      determined by serum hs-CRP is significantly increased in children with type 1
      diabetes, and even more pronounced in apparently healthy juveniles with obesity.
      The increased IMT of CCAs strongly argues for an association between this low
      grade inflammation and early atherosclerotic vessel injury.

PMID- 15239024
TI  - Identification of influencing variables on adiponectin serum levels in diabetes
      mellitus type 1 and type 2.
AB  - BACKGROUND: Adiponectin represents an adipocyte-specific secretory protein that
      has been discussed recently as candidate gene and promising new drug target to
      restore insulin sensitivity in diabetes mellitus type 2. AIM: The aim of the
      present study was to define influencing variables on adiponectin serum levels in
      a large cohort of caucasian patients with type 1/type 2 diabetes and healthy
      controls. Additionally, adiponectin gene polymorphisms (Tyr111His and Gly15Gly)
      were investigated for possible associations with adiponectin serum levels.
      METHODS: Adiponectin serum concentrations were measured in a metabolically well
      characterized cohort of 892 caucasian patients (556 with type 2 diabetes, 118
      with type 1 diabetes, 218 controls) by ELISA. Gene polymorphisms were determined
      by PCR-based RFLP. RESULTS: 1) Adiponectin values are dependent on gender with
      higher levels in diabetic females than in diabetic males. This gender-specific
      effect was only restricted to patients with diabetes and cannot be observed in
      controls. 2) In contrast to previous studies, the presence of diabetes does not
      influence adiponectin serum levels after correction for BMI. In addition, age has
      no influence on adiponectin levels. 3) Adiponectin levels are dependent on renal
      function at a creatinine clearance < 45 ml/min. 4) Regression analysis showed a
      significant, but only weak correlation between BMI and adiponectin in patients
      with diabetes mellitus type 2 (r = 0.47) and type 1 (r = 0.57). 5) Adiponectin
      gene polymorphisms (Tyr111His and Gly15Gly) do not influence adiponectin levels.
      CONCLUSIONS: Adiponectin serum concentrations can only be interpreted after
      careful correction for gender and renal function, whereas the genetic variants
      Tyr11His and Gly15Gly do not seem to play a role. The correlation between BMI and
      adiponectin was weaker than expected in diabetic patients.

PMID- 15239025
TI  - A stable prostacyclin analogue reduces high serum TNF-alpha levels in diabetic
      patients.
AB  - AIMS: To confirm whether a prostacyclin (prostaglandin I (2)) affects the
      increased TNF-alpha concentration in sera of diabetic patients, we measured serum
      TNF-alpha concentration and treated these patients with oral administration of
      the stable prostacyclin analogue (Beraprost). Twelve of 20 type II diabetic
      patients were investigated for follow up-study and 6 of those patients were for
      therapy with Beraprost for diabetic neuropathy. SUBJECTS AND METHODS: Serum TNF
      alpha concentration was quantified by EASIA using monoclonal antibodies directed
      against distinct epitopes of TNF-alpha. RESULTS: In diabetic patients, serum TNF
      alpha concentration was significantly increased compared with that of healthy
      subjects. The augmented TNF-alpha concentration in these patients was not
      decreased by diabetic control using antihyperglycemic agents for 8 weeks but was
      reduced with oral administration of a stable prostacyclin (prostaglandin I (2))
      analogue for 5 weeks without any changes of blood glucose levels. CONCLUSIONS:
      Stable prostacyclin analogue administration for a short term period reduced
      increased TNF-alpha levels in diabetic patients, not through the improved
      hyperglycemic condition but another pathway, probably a cAMP system. These
      results imply that treatment with the prostacyclin analogue may contribute to the
      prevention of progression in diabetic complications.

PMID- 15239026
TI  - Enhancement of early- and late-phase insulin secretion and insulin sensitivity by
      the combination of repaglinide and metformin in type 2 diabetes mellitus.
AB  - The effects of a combination of repaglinide and metformin on the insulin
      secretion pattern and insulin sensitivity were studied in a fixed-dose, open
      label, placebo-controlled cross-over study. Eleven patients with T2 DM were
      allocated in random order to treatment with placebo or repaglinide (1 mg pre-meal
      3 x/day) in combination with metformin (2550 mg/day) for one-week periods of
      each. At the end of each period a hyperglycaemic (HC) and a euglycaemic clamp
      (EC) were performed. Both early (0 - 10 min) and late (25 - 180 min) phases of
      insulin secretion were significantly increased during HC with repaglinide
      compared to placebo (263.3 +/- 133.1 vs. 443.6 +/- 138.5 pmol/l/10 min, p = 0.008
      and 18 750.9 +/- 5936.4 vs. 34 508.65 +/- 9234.0 pmol/l/25 - 180 min; p = 0.008).
      The C-peptide concentrations under steady-state conditions were lower in EC with
      placebo than with repaglinide (p = 0.014). When euglycaemia was achieved in EC,
      the C-peptide concentrations decreased from hyperglycaemic to normoglycaemic
      values in the presence of repaglinide but remained higher than after placebo. The
      insulin sensitivity index (ISI) was increased by 35 % after 1 week of combination
      therapy with repaglinide plus metformin (1.11 +/- 0.03 x 10 (2) vs. 0.83 +/- 0.21
      x 10 (2) mg x kg (-1) body weight x min (-1) x pmol (-1) x l, respectively; p =
      0.033). Repaglinide increased early and late phases of insulin responses in HC,
      without markedly enhancing insulin secretion in euglycaemia. Repaglinide in
      combination with metformin produced a significant enhancement of ISI, suggesting
      a synergistic effect on insulin sensitivity.

PMID- 15239027
TI  - Postoperative complications of thyroidectomy for differentiated thyroid
      carcinoma.
AB  - OBJECTIVE: This study evaluates the incidence and risk factors of complications
      in patients submitted to thyroidectomy for differentiated thyroid carcinoma in a
      cancer hospital with residency training. STUDY DESIGN: A retrospective chart and
      complications review of 316 consecutive patients who underwent thyroidectomy for
      differentiated thyroid carcinoma. RESULTS: Of the 316 patients, the main
      postoperative complications were transient hypocalcemia in 87 (27.5%), permanent
      hypocalcemia in 16 (5.1%), transient vocal cord palsy in 4 (1.2%), and permanent
      vocal cord palsy in 2 (0.6%). Neck dissection and paratracheal lymph node
      dissection when associated with total thyroidectomy were significantly related to
      transitory and permanent hypocalcemia. CONCLUSION: Thyroid surgery can be
      performed safely in a hospital with medical residency training program under
      direct supervision of an experienced surgeon with acceptable morbidity.
      Hypocalcemia is the most significant complication. Neck and paratracheal lymph
      node dissections were the most significant predictors of hypocalcemia in patients
      submitted to total thyroidectomy.

PMID- 15239028
TI  - Prognostic significance of p53 and FHIT in advanced oropharyngeal carcinoma.
AB  - OBJECTIVE: To determine the prognostic significance of p53 and fragile histidine
      triad (FHIT) expression in advanced oropharyngeal squamous cell carcinoma. STUDY
      DESIGN: A retrospective collection of clinical data was correlated with the
      protein expression. METHOD: The expression of p53 and FHIT in specimens from
      patients with previously untreated advanced squamous cell carcinoma of the
      oropharynx was determined by immunohistochemistry. The expression of p53 and FHIT
      was statistically correlated with survival outcome. The primary endpoints were
      overall survival and disease-free survival. RESULTS: Thirty-four patients were
      analyzed in this study. Overexpression of p53 was observed in 41.2% (14/34) of
      tumors and was associated with a trend toward an improved overall survival using
      univariate (P =.1088, risk ratio [RR] = 0.503) and multivariate (P =.1533, RR =
      0.470) analyses. Marked reduction or complete absence of FHIT expression was
      observed in 57.6% (19/33) of tumors. Patients with tumors showing no reduction in
      FHIT expression had a lower overall survival using univariate (P =.04, RR = 2.27)
      and multivariate (P =.013, RR = 4.41) analyses. CONCLUSION: Overexpression of p53
      predicted a trend toward an improved prognosis, whereas no reduction in FHIT
      expression predicted a significantly poorer outcome in patients with advanced
      oropharyngeal cancer.

PMID- 15239029
TI  - Value of minimal residual disease in patients with early cancer of the tongue.
AB  - PURPOSE: The clinical course of patients with squamous cell carcinoma (SCC) of
      the tongue is often unpredictable. Some patients have a fair course with good
      response to treatment, whereas others have aggressive locoregional disease
      despite diagnosis at an early stage. The purpose of the present study was to
      determine if histochemical staining for cytokeratins of the negative neck nodes
      obtained in prophylactic neck dissection could predict treatment failure in
      patients with SCC of the tongue. MATERIALS AND METHODS: Between 1990 and 2000, 18
      patients with early squamous cell carcinoma of the tongue (T1,T2N0M0) underwent
      partial glossectomy with neck dissection at the Rabin Medical Center in Israel.
      All had clear resection margins and no evidence of neck metastasis and were
      expected to do well. Nevertheless, 6 patients had an aggressive course and died
      of disease shortly after presentation because of local or regional failure. In an
      attempt to predict failure of treatment and patients' outcome, paraffin-embedded
      blocks from the pathologically negative lymph nodes were subjected to
      immunohistochemical staining for cytokeratin using polyclonal antibodies. The
      antigen-antibody complex was identified by using the biotinylated secondary
      antibody and followed by the streptavidin-peroxidase detection method. RESULTS:
      None of the 142 sections from pathologically negative lymph nodes stained
      positive for keratin. On multivariate analysis, a statistically significant
      relationship was found between disease-free survival, early recurrence (P =.03),
      and metastasis to the neck (P =.008). CONCLUSIONS: Keratin staining failed to
      yield evidence of micrometastasis. Further studies with more samples are needed
      to confirm these findings.

PMID- 15239030
TI  - Clinical guidelines, defensive medicine, and the physician between the two.
AB  - PURPOSE: In this article, we study the use of the American Academy of
      Otolaryngology-Head and Neck Surgery recommendations regarding coagulation
      screening tests before tonsillectomy and adenoidectomy by ear, nose, and throat
      (ENT) physicians in Israel and offer insights into the reasons for
      accepting/declining this recommendation. MATERIALS AND METHODS: During April and
      May 2002, 309 self-administered questionnaires were sent to all ENT physician
      members of the Israeli Society of Otolaryngology-Head and Neck Surgery.
      Physicians answered questions regarding demographic data, their habits of
      preoperative laboratory and imaging tests before tonsillectomy and adenoidectomy,
      and the reasons for performing these tests. RESULTS: One hundred ninety-six
      (63.4% compliance rate) physicians responded to the survey. One hundred fifty
      four (78.6% of the responding physicians) do not follow guideline recommendations
      and ask their otherwise healthy patients to undergo prothrombin time/partial
      thromboplastin time (PT/PTT) tests before tonsillectomy and adenoidectomy. Common
      practice in their departments was the leading reasoning for preoperative PT/PTT
      testing for 101 (51.5%) physicians. Eighty-nine physicians (45.4%) specifically
      stated that the reason for this behavior is defensive medicine, thirty-two
      physicians (16.3%) stated that the reason for those tests is hospital
      requirements, and literature recommendation was the reason in 24 (12.2%),
      followed by personal experience for 11 physicians (5.6%). CONCLUSIONS: Most ENT
      physicians in Israel do not follow clinical guidelines and perform unnecessary
      coagulation tests before tonsillectomy and adenoidectomy. More studies are needed
      to find ways to change physicians' behavior regarding preoperative tests.

PMID- 15239031
TI  - A refractory case of erythromelalgia involving the ears.
AB  - Erythromelalgia is a rare syndrome that is characterized by episodic attacks of
      burning pain, erythema, and increased temperature usually affecting the
      extremities, which is aggravated by warmth or exercise. We describe a patient
      with a 3-year history of refractory burning pain and red ears. A review of
      clinical features, disease classification, associated diseases, and treatment of
      this disease is presented.

PMID- 15239032
TI  - Metastatic renal cell carcinoma to the nasal cavity.

PMID- 15239033
TI  - Cerebro-costo-mandibular syndrome presenting as Pierre Robin sequence.
AB  - Cerebro-costo-mandibular syndrome is a rare disorder characterized by psychomotor
      retardation, posterior rib-gap defects, and the orofacial defects of Pierre Robin
      sequence. Most cases are sporadic, but several familial cases have been reported,
      many of which support autosomal recessive inheritance. We present a case of
      autosomal dominant inheritance from father to son; the seventh known case of
      dominant transmission. We also review the findings, inheritance pattern, and
      outcomes of Pierre Robin sequence that are useful in managing affected patients.

PMID- 15239034
TI  - Coxiella burnetii: an unusual ENT pathogen.
AB  - Coxiella burnetii, the causative agent of Q fever, is a prevalent zoonotic
      disease manifestating usually as atypical pneumonia or hepatitis. We describe 2
      cases of serologically proven infection by Coxiella burnetii whose primary
      manifestations arose from the upper respiratory tract and were initially referred
      to the ear, nose, and throat (ENT) department. This is the first related report
      in medical literature. A 20-year-old woman with fever, bilateral tonsillitis,
      lymphadenopathy, and mild aminotransferase elevation, and a 30-year old man with
      spiking fever and laryngitis are presented. Diagnosis in both cases was achieved
      through evolving serological response to Coxiella burnetii. The importance of
      including the pathogen in the differential diagnosis of ENT patients, in assorted
      epidemiological settings, and the significance of the proper antibiotic selection
      are further discussed.

PMID- 15239035
TI  - Lipoblastoma of the neck: a case report and literature review.
AB  - Lipoblastoma is a rare benign tumor arising from embryonic white fat. We describe
      a case of huge lipoblastoma of the neck in a 1-year-old boy. Magnetic resonance
      imaging (MRI) revealed a 7 x 7 cm neck mass that extruded into the parapharyngeal
      and paratracheal spaces. At the operation, a well-circumscribed and extensively
      growing tumor was completely removed. Histopathologic examination showed that the
      tumor contained lobulated mature adipose tissue and myxoid tissue with lipoblasts
      and other immature fat cells. The postoperative course was uneventful, and no
      recurrence of tumor has been noted in more than 2 years follow-up.

PMID- 15239036
TI  - Malignant granular cell tumor in larynx mimicking laryngeal carcinoma.
AB  - A 72-year-old man presented to our clinic with progressed husky voice, dysphagia
      and globus pharyngeus. Fiberoptic laryngoscopy showed a large subglottic mass
      with an irregular surface. A chest roentgenogram revealed multiple nodules over
      the right upper and lower lobes. Under the impression of malignant laryngeal
      tumor with lung metastasis, he underwent direct laryngeal biopsy and excision.
      Pathologic findings showed malignant granular cell tumor. Postoperative
      palliative chemotherapy was done for his lung metastasis. The multiple pulmonary
      nodules were decreased in size and number but not complete remission. The
      laryngeal tumor has not recurred after a 14-month follow-up.

PMID- 15239037
TI  - Chondrosarcoma of the sphenoid sinus resected by an endoscopic approach.
AB  - Chondrosarcoma of the sinonasal tract is a rare neoplasm. Surgical excision is
      usually sufficient for low-grade lesions, whereas combined treatment is usually
      recommended for high-grade lesions. The oncologic outcome depends on a complete
      resection as well as the grade of the tumor. We present the case of a 35-year-old
      man presenting with an incidental finding of a chondrosarcoma of the posterior
      septum and rostrum of the sphenoid sinus. The tumor was completely resected using
      a transnasal endoscopic approach obtaining negative margins. Surgery is the
      mainstay treatment for low-grade chondrosarcomas. In selected patients, complete
      resection can be achieved using transnasal endoscopic approaches.

PMID- 15239038
TI  - High-pressure grease injury of the face.
AB  - We describe a rare case of high-pressure grease injury of the face in a 48-year
      old man with severe facial edema, soft palate swelling, and bleeding from the
      nose and mouth. Preoperative computed tomography (CT) revealed multiple low
      density areas in nasal cavity, subcutaneous tissue of the cheek, soft palate,
      right maxillary sinus, and right infratemporal fossa. The patient complained of a
      dyspnea feeling, and immediate tracheostomy was performed. The grease was removed
      by the Caldwell-Luc incision approach but was partially left in the infratemporal
      fossa. After the operation, the patient still complained cheek and temporal pain.
      CT and magnetic resonance imaging were useful to diagnose the remaining grease,
      and the remnant of the grease was completely removed by the Weber-Fergusson
      incision approach.

PMID- 15239039
TI  - Respiratory epithelial adenomatoid hamartoma associated with nasal polyposis.
AB  - Hamartoma is a rare, non-neoplastic tumor characterized by an abnormal mixture of
      tissues, which are indigenous to the region. They are rare in the nasal cavity.
      We report a 79-year-old woman with an adenomatoid hamartoma in the left nasal
      cavity associated with nasal polyposis. This association supports the hypothesis
      that inflammation is one of the factors that induce the development of a
      hamartoma. Functional endoscopic sinus surgery was performed to completely remove
      it, and this lesion was found to have arisen from the lateral nasal wall. It is
      an unusual localization because the most common site in the nasal cavity is the
      nasal septum, particularly the posterior aspect. Limited but complete surgical
      resection is the treatment of choice. Although adenomatoid hamartoma arising from
      the sinonasal tract is very rare, head and neck surgeons should be aware of this
      pathological entity as a differential diagnosis for inverted papilloma and
      adenocarcinoma. Misinterpretation of these lesions as a true neoplasm may result
      in unnecessarily aggressive surgery for this benign lesion.

PMID- 15239040
TI  - Occult contralateral congenital cholesteatoma: is the epidermoid formation theory
      enough?
AB  - Bilateral congenital cholesteatomas are rare entities. Nine cases have been
      previously described in the literature. Many different etiologies for the
      development of congenital cholesteatoma have been proposed. The case of a five
      year-old boy with bilateral congenital cholesteatoma is discussed. A lesion of
      the left ear was apparent clinically. However, the right-sided lesion was silent
      and was demonstrated only by radiologic exam. Theories of pathogenesis are
      reviewed.

PMID- 15239041
TI  - Spontaneous pneumomediastinum presenting with retropharyngeal emphysema.
AB  - Spontaneous pneumomediastinum is a rare condition that may follow increases in
      intrathoracic pressure. Patients may present with symptoms isolated to the head
      and neck. Although this condition is usually benign, there are other potentially
      fatal conditions, which often present similarly and clinically are difficult to
      differentiate from this entity. Despite this condition being described in the
      thoracic and medical literature, very little is found in the otolaryngological
      literature. This article reports 4 cases in which presenting symptoms were
      limited to the head and neck and otolaryngologists were the initial consultants.
      This highlights the need for otolaryngologists to be aware of this clinical
      entity.

PMID- 15239045
TI  - Strategies for facilitated forward chemical genetics.

PMID- 15239042
TI  - Secreting vagal paraganglioma.
AB  - Paragangliomas are rare tumors that derive from neural crest tissue. Vagal
      paragangliomas account for only 3% of all head and neck paragangliomas. Patients
      with vagal paragangliomas typically present with an asymptomatic neck mass and,
      less frequently, with cranial neuropathies. It is estimated that only 1% to 3% of
      all head and neck paragangliomas secrete catecholamines. The incidence of
      secreting vagal paragangliomas is even smaller. The diagnosis of a secreting
      paraganglioma involves the use of a screening test for serum catecholamines and a
      24-hour urinary test for catecholamine metabolites. The identification and
      staging of these tumors can be performed through the use of MRI and/or CT scans
      and an octreotide scintigraphy. The mainstay treatment is surgical extirpation;
      however, preoperative medical blockade is critical to avoid a hypertensive crisis
      intra-operatively. We present two illustrative cases of secreting vagal
      paragangliomas involving a complex diagnostic and therapeutic algorithm.

PMID- 15239046
TI  - Site-specific incorporation of unnatural amino acids into proteins.

PMID- 15239047
TI  - Evolutionary biology and chemical geology: a timely marriage.
AB  - For more than 150 years natural selection has been perceived to be the
      overwhelming force in evolution. Only in recent decades have we obtained new
      insights into environmental and physicochemical factors that participate with
      selection in a synergic way. Far from denying Darwin's theory, such neglected
      factors put order to the bewildering range of genotypes and morphologies found in
      living organisms and, more importantly, they place evolution in a planetary
      context where biology, geology, and chemistry can easily be integrated.

PMID- 15239048
TI  - A mass spectrometry plate reader: monitoring enzyme activity and inhibition with
      a Desorption/Ionization on Silicon (DIOS) platform.
AB  - A surface-based laser desorption/ionization mass spectrometry assay that makes
      use of Desorption/Ionization on Silicon Mass Spectrometry (DIOS-MS) has been
      developed to monitor enzyme activity and enzyme inhibition. DIOS-MS has been used
      to characterize inhibitors from a library and then to monitor their activity
      against selected enzyme targets, including proteases, glycotransferase, and
      acetylcholinesterase. An automated DIOS-MS system was also used as a high
      throughput screen for the activity of novel enzymes and enzyme inhibitors. On two
      different commercially available instruments, a sampling rate of up to 38
      inhibitors per minute was accomplished, with thousands of inhibitors being
      monitored. The ease of applying mass spectrometry toward developing enzyme assays
      and the speed of surface-based assays such as DIOS for monitoring inhibitor
      effectiveness and enzyme activity makes it attractive for a broad range of
      screening applications.

PMID- 15239049
TI  - Cotranslational incorporation of a structurally diverse series of proline
      analogues in an Escherichia coli expression system.
AB  - A set of Escherichia coli expression strains have been defined that are competent
      for the incorporation of a structurally diverse series of proline analogues under
      culture conditions that are compatible with high levels of analogue substitution
      within a proline-rich protein substrate. These bacterial strains have been
      employed to assay the efficacy of incorporation of noncanonical amino acids into
      a recombinant-protein test substrate and to create variant polypeptides in which
      native protein sequences have been globally substituted with imino acid analogues
      in response to proline codons. We envision that these methods may be used to
      interrogate the effect of imino acid substitution on protein structure and
      function and may be particularly informative in the context of structural
      comparison of a series of modified proteins with respect to the stereoelectronic
      differences between the incorporated proline analogues.

PMID- 15239050
TI  - Surface plasmon resonance evaluation of various aminoglycoside-RNA hairpin
      interactions reveals low degree of selectivity.
AB  - Aminoglycoside antibiotics, which are able to selectively bind to RNA, are
      considered to be an important lead in RNA-targeting drug discovery. In this
      study, surface plasmon resonance (SPR) was employed to explore the interaction of
      aminoglycosides with known tobramycin-binding RNA hairpins (aptamers) and an
      unrelated RNA hairpin. It was established that aminoglycosides have multiple
      interactions with RNA hairpins. Unexpectedly, the different hairpins showed
      comparable affinity for a set of related aminoglycosides. The observed absence of
      selectivity presents an extra hurdle in the discovery of novel aminoglycosides as
      specific drugs that target defined RNA hairpins.

PMID- 15239051
TI  - Amplified telomerase analysis by using rotating magnetic particles: the rapid and
      sensitive detection of cancer cells.
AB  - A highly sensitive telomerase detection method that involves amplified telomerase
      analysis and the use of rotating magnetic particles has been developed. Magnetic
      particles, functionalized with a primer (1) that is recognized by telomerase, are
      mixed with a nucleotide mixture that includes biotinylated-dUTP, and telomerase
      induced elongation of the primers proceeds with simultaneous biotin
      incorporation. Avidin-Horseradish peroxidase conjugate, coupled to biotin labels,
      yields the biocatalytic functional particles. Mixing the resulting particles with
      naphthoquinone-modified magnetic particles enables the optoelectronic detection
      of telomerase. Attraction of the magnetic particles to an electrode, followed by
      rotation of the particles, causes the electrocatalytic reduction of O(2) to
      H(2)O(2) and HRP-catalyzed oxidation of luminol (3); this results in
      chemilumunescence. The intensity of the emitted light depends on the telomerase
      content of the sample and the rotation speed of the particles. A minimum number
      of 10 cancer cells could be detected.

PMID- 15239053
TI  - Cytosine detection by a fluorescein-labeled probe containing base-discriminating
      fluorescent nucleobase.
AB  - We report on a new method for the detection of a base at a specific site in a DNA
      sequence by monitoring the fluorescence emission of fluorescein. To achieve this
      goal, we developed a new base-discriminating fluorescent (BDF) nucleobase,
      naphthodeazaadenine ((ND)A). The fluorescence spectrum of the duplex possessing a
      cytosine base as a complementary base of (ND)A showed a fluorescence peak at 383
      nm when using an excitation wavelength of 350 nm. When the complementary base of
      (ND)A was one of the other bases, the fluorescence intensity was very low. The
      fluorescence emission spectrum of (ND)A overlapped with the fluorescence
      excitation spectrum of fluorescein in the wavelength range of 400-500 nm. Thus,
      we designed FRET-BDF probes containing (ND)A as the FRET donor and fluorescein as
      the acceptor. The interaction of these two fluorophores, which are separated by
      defined base pairs, allowed an efficient energy transfer that resulted in a
      dominant fluorescence emission of fluorescein at 520 nm when using an excitation
      wavelength of 350 nm. Fluorescence emission from FRET-BDF probes was observed
      only when the complementary base of (ND)A is C, thus achieving a clear
      distinction of a C base on the complementary DNA strand. However, the general
      utility of our method is limited due to the quenching of the (ND)A fluorescence
      by a G/C base pair flanking (ND)A.

PMID- 15239052
TI  - Electronic transduction of HIV-1 drug resistance in AIDS patients.
AB  - A drug composition consisting of nucleoside reverse transcriptase inhibitors
      (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease
      inhibitors (PIs) is commonly used in AIDS therapy. A major difficulty encountered
      with the therapeutic composite involves the emergence of drug-resistant viruses,
      especially to the PIs, regarded as the most effective drugs in the composition.
      We present a novel bioelectronic means to detect the appearance of mutated HIV-1
      exhibiting drug resistance to the PI saquinavir. The method is based on the
      translation of viral RNA, the association of cleaved or uncleaved Gag
      polyproteins at an electrode surface functionalized with the respective
      antibodies, and the bioelectronic detection of the Gag polyproteins associated
      with the surface. The bioelectronic process includes the association of anti-MA
      or anti-CA antibodies, the secondary binding of an antibody-horseradish
      peroxidase (HRP) conjugate, and the biocatalyzed precipitation of an insoluble
      product on the electronic transducers. Faradaic impedance measurements and quartz
      crystal microbalance analyses are employed to follow the autoprocessing of the
      Gag polyproteins. The method was applied to determine drug resistance in infected
      cultured cells and also in blood samples of consenting AIDS patients. The method
      described here is also applicable to the determination of drug effectiveness in
      AIDS patients and to screening of the efficiency of newly developed drugs.

PMID- 15239054
TI  - Design and characterisation of an artificial DNA-binding cytochrome.
AB  - We aim to design novel proteins that link specific biochemical binding events,
      such as DNA recognition, with electron transfer functionality. We want these
      proteins to form the basis of new molecules that can be used for templated
      assembly of conducting cofactors or for thermodynamically linking DNA binding
      with cofactor chemistry for nanodevice applications. The first examples of our
      new proteins recruit the DNA-binding basic helix region of the leucine zipper
      protein GCN4. This basic helix region was attached to the N and C termini of
      cytochrome b(562) (cyt b(562)) to produce new, monomeric, multifunctional
      polypeptides. We have fully characterised the DNA and haem-binding properties of
      these proteins, which is a prerequisite for future application of the new
      molecules. Attachment of a single basic helix of GCN4 to either the N or C
      terminus of the cytochrome does not result in specific DNA binding but the
      presence of DNA-binding domains at both termini converts the cytochrome into a
      specific DNA-binding protein. Upon binding haem, this chimeric protein attains
      the spectral characteristics of wild-type cyt b(562). The three forms of the
      protein, apo, oxidised holo and reduced holo, all bind the designed (ATGAcgATGA)
      target DNA sequence with a dissociation constant, K(D), of approximately 90 nM.
      The protein has a lower affinity (K(D) ca. 370 nM) for the wild-type GCN4
      recognition sequence (ATGAcTCAT). The presence of only half the consensus DNA
      sequence (ATGAcgGGCC) shifts the K(D) value to more than 2500 nM and the chimera
      does not bind specifically to DNA sequences with no target recognition sites.
      Ultracentrifugation revealed that the holoprotein-DNA complex is formed with a
      1:1 stoichiometry, which indicates that a higher-order protein aggregate is not
      responsible for DNA binding. Mutagenesis of a loop linking helices 2 and 3 of the
      cytochrome results in a chimera with a haem-dependent DNA binding affinity. This
      is the first demonstration that binding of a haem group to a designed monomeric
      protein can allosterically modulate the DNA binding affinity.

PMID- 15239055
TI  - Enhanced fructose oxidase activity in a galactose oxidase variant.
AB  - Galactose oxidase (GO; EC 1.1.3.9) catalyses the oxidation of a wide range of
      primary alcohols including mono-, oligo- and polysaccharides. High-resolution
      structures have been determined for GO, but no structural information is
      available for the enzyme with bound substrate or inhibitor. Previously, computer
      aided docking experiments have been used to develop a plausible model for
      interactions between GO and the D-galactose substrate. Residues implicated in
      such interactions include Arg330, Gln406, Phe464, Phe194 and Trp290. In the
      present study we describe an improved expression system for recombinant GO in the
      methylotrophic yeast Pichia pastoris. We use this system to express variant
      proteins mutated at Arg330 and Phe464 to explore the substrate binding model. We
      also demonstrate that the Arg330 variants display greater fructose oxidase
      activity than does wild-type GO.

PMID- 15239056
TI  - Enantiocomplementary enzymatic resolution of the chiral auxiliary: cis,cis-6-(2,2
      dimethylpropanamido)spiro[4.4]nonan-1-ol and the molecular basis for the high
      enantioselectivity of subtilisin Carlsberg.
AB  - cis,cis-(+/-)-6-(2,2-Dimethylpropanamido)spiro[4.4]nonan-1-ol, 1, a chiral
      auxiliary for Diels-Alder additions, was resolved by enzyme-catalyzed hydrolysis
      of the corresponding butyrate and acrylate esters. Subtilisin Carlsberg protease
      and bovine cholesterol esterase both showed high enantioselectivity in this
      process, but favored opposite enantiomers. Subtilisin Carlsberg favored esters of
      (1S,5S,6S)-1, while bovine cholesterol esterase favored esters of (1R,5R,6R)-1,
      consistent with the approximately mirror-image arrangement of the active sites of
      subtilisins and lipases/esterases. A gram-scale resolution of 1-acrylate with
      subtilisin Carlsberg yielded (1S,5S,6S)-1 (1.1 g, 46 % yield, 99 % ee) and
      (1R,5R,6R)-1-acrylate (1.3 g, 44 % yield, 99 % ee) although the reaction was
      slow. The high enantioselectivity combined with the conformational rigidity of
      the substrate made this an ideal example to identify the molecular basis of the
      enantioselectivity of subtilisin Carlsberg toward secondary alcohols. When
      modeled, the favored (1S,5S,6S) enantiomer adopted a catalytically productive
      conformation with two longer-than-expected hydrogen bonds, consistent with the
      slow reaction rate. The unfavored (1R,5R,6R) enantiomer encountered severe steric
      interactions with catalytically essential residues in the model. It either
      distorted the catalytic histidine position or encountered severe steric strain
      with Asn155, an oxyanion-stabilizing residue.

PMID- 15239057
TI  - Mechanistic implications of Escherichia coli galactokinase structure-based
      engineering.

PMID- 15239058
TI  - Structure-based enhancement of the first anomeric glucokinase.

PMID- 15239060
TI  - Enzymatic cyclisation of peptidomimetics with incorporated (E)-alkene dipeptide
      isosteres.

PMID- 15239059
TI  - Structure-based design, synthesis, and in vitro evaluation of nonpeptidic
      neprilysin inhibitors.

PMID- 15239061
TI  - The molecular arrangement of membrane-bound annexin A2-S100A10 tetramer as
      revealed by scanning force microscopy.

PMID- 15239062
TI  - Branches on the alpha-C atom of cyclosporin A residue 3 result in direct
      calcineurin inhibition and rapid cyclophilin 18 binding.

PMID- 15239063
TI  - Synthesis and phenotypic screening of a Guanine-mimetic library.

PMID- 15239064
TI  - Proofreading activity of Pfu thermostable DNA polymerase on a 6-O-methylguanine
      containing template monitored by ESI-FTICR mass spectrometry.

PMID- 15239067
TI  - Theoretical reassessment of Whelk-O1 as an enantioselective receptor for 1-(4
      halogeno-phenyl)-1-ethylamine derivatives.
AB  - A combination of molecular mechanics and first principles calculations was used
      to explore the enantioselectivity of receptors, taking into account experimental
      data from the CHIRBASE database. Interactions between the Whelk-O1 HPLC chiral
      stationary phase with the complete series of 1-(4-halogeno-phenyl)-1-ethylamine
      derivative racemates were studied. The objective was to extract information from
      the interactions between the chiral Whelk-O1 stationary phase and the
      enantiomers, hence probing the origin of the enantioselective behavior.
      Calculations correctly reproduce the elution orders and reasonably describe the
      experimental enantioselectivities and retention factors. Different binding modes
      were observed for the first eluted enantiomer complexes, whereas the second
      eluted show only one prevalent diastereomeric binding fashion. Natural bond
      orbital (NBO) analysis was used on the global minima bound-complexes to quantify
      donor-acceptor interactions among chiral stationary phase and ligand moieties.
      Intermolecular hydrogen bonding was found to be the essential energetic
      interaction for all systems studied. CH-pi, aromatic stacking and various charge
      transfer interactions were found to be smaller in magnitude but still important
      for the global enantioselective behavior. The three-point interaction model is
      discussed, pointing out the difficulty of its application for the qualitative
      prediction of elution orders (absolute configurations).

PMID- 15239068
TI  - Chirality induction on achiral N-methyl aromatic amide oligomers bearing terminal
      carboxy groups with chiral amines.
AB  - Novel unsymmetrical N-methyl aromatic amide oligomers bearing two carboxy groups
      at both ends were synthesized and their complexation with various optically
      active amines in solution was investigated using circular dichroism (CD)
      spectroscopy. The complexes showed a characteristic induced CD in the absorption
      region due to the aromatic amide reflecting the absolute configuration of the
      chiral amines.

PMID- 15239069
TI  - Alcohol-O,O'-dibenzoyl-(2R,3R)-tartaric acid complexes.
AB  - Structures of chiral and achiral alcohol-O,O'-dibenzoyl-(2R,3R)-tartaric acid
      (DBTA) complexes were investigated by single-crystal X-ray diffraction (seven new
      crystal structures were determined). The complexes contain DBTA and chiral
      alcohol in 1:1, DBTA and achiral alcohol in 1:2 host-guest stoichiometry. The
      hydrogen bonding structures of chiral alcohol-DBTA and achiral alcohol-DBTA
      complexes are different, but within a subclass they are isostructural ones.

PMID- 15239070
TI  - Programmed assembly of rigid-rod beta-barrel pores: thermal inversion of
      chirality.
AB  - The programmed assembly of p-octiphenyl rods carrying six complementary
      tripeptide strands was studied in the presence of bilayer membranes using
      circular dichroism (CD) spectroscopy. Thermal CD experiments demonstrated
      programmed assembly of anionic and cationic rods into supramolecules at low
      temperature that irreversibly transform into more stable supramolecules at
      intermediate and high temperature. Higher activation energies for programmed
      assembly with rods containing multiple guanidinium rather than ammonium cations
      was consistent with stabilization by guanidinium-anion complexes. Qualitative
      thermal inversion of supramolecular chirality during programmed assembly was
      detected continuously. Inversion of supramolecular chirality occurred with
      decreasing solvent polarity as well.

PMID- 15239071
TI  - Chiral discrimination between thalidomide enantiomers using a solid surface with
      two-dimensional chirality.
AB  - Chiral discrimination between thalidomide enantiomers was achieved using the self
      assembled monolayer (SAM) of an atropisomeric compound, 1,1'-binaphthalene-2,2'
      dithiol (BNSH), which takes a two-dimensional chiral arrangement on gold(111)
      surface. Interestingly, an "all-or-none" type enantioselectivity appears; one
      enantiomeric form of BNSH SAM allows the adsorption of only one enantiomer of
      thalidomide. In addition, the response of a racemic SAM of BNSH was revealed to
      be one-half of that caused by pure enantiomeric SAM.

PMID- 15239072
TI  - Synthesis of new chiral phosphorous- and nitrogen-containing ligands from resin
      acids.
AB  - Starting from the phytogenic diterpenes, chiral phosphine, urea, and thiourea
      derivatives were synthesized. Using these new chiral ligands, Rh(I) and Ru(II)
      complexes were prepared and used as catalysts for the catalytic asymmetric
      hydrogenation of unsaturated carboxylic acids and asymmetric hydrogen-transfer
      reduction of carbonyl compounds. Although the enantiopurity of the products
      obtained was not high, it was demonstrated that chiral ligands derived from
      diterpenes could be used for asymmetric reduction.

PMID- 15239073
TI  - Enantioseparation of tiropramide by HPLC.
AB  - Tiropramide is an antispasmodic drug that has a chiral center. Resolution of
      tiropramide enantiomers on various kinds of chiral stationary phases was
      performed by HPLC. A good resolution on a leucine-derived chiral stationary phase
      was found. An improved chromatographic condition to resolve racemic tiropramide
      on the CSP was examined by changing the flow rate, composition, and kind of
      mobile phases.

PMID- 15239074
TI  - Dispersion of anomalous azimuthal rotation and circular extinction contrast in
      dyed K(2)SO(4) crystals.
AB  - We present measurements of the dispersion of anomalous azimuthal rotation signals
      from dyed crystals that are at variance with our predictions based on a model of
      these effects predicated on the predominance of Rayleigh scattering from isolated
      dye molecules (Kaminsky et al. J Phys Chem A 107:2800-2807, 2003). Here, we
      extend our scattering model to include the effects of the absorption and
      refraction of individual dyes that are inclined in a biased manner with respect
      to the eigenmodes of the medium. Our revised model describes the wavelength
      dependence of the rotations. It is likely that absorption, refraction, and
      Rayleigh scattering are all manifest, with absorption and refraction being the
      leading effects.

PMID- 15239075
TI  - Conflicting interests and publication in Hepatology.

PMID- 15239078
TI  - Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of
      hepatic failure.
AB  - Acetaminophen overdose is the leading cause for calls to Poison Control Centers
      (>100,000/year) and accounts for more than 56,000 emergency room visits, 2,600
      hospitalizations, and an estimated 458 deaths due to acute liver failure each
      year. Data from the U.S. Acute Liver Failure Study Group registry of more than
      700 patients with acute liver failure across the United States implicates
      acetaminophen poisoning in nearly 50% of all acute liver failure in this country.
      Available in many single or combination products, acetaminophen produces more
      than 1 billion US dollars in annual sales for Tylenol products alone. It is
      heavily marketed for its safety compared to nonsteroidal analgesics. By enabling
      self-diagnosis and treatment of minor aches and pains, its benefits are said by
      the Food and Drug Administration to outweigh its risks. It still must be asked:
      Is this amount of injury and death really acceptable for an over-the-counter pain
      reliever?

PMID- 15239079
TI  - Acetaminophen misconceptions.
AB  - Examination of the pharmacokinetics of acetaminophen can decrease misconceptions
      involved in clinical evaluation. Enzyme patterns and acetaminophen levels must be
      related to time and known metabolic phenomena. A careful look at ethanol and
      nutrition, especially fasting demonstrates that therapeutic doses of
      acetaminophen do not place patients at a greater risk in either of these
      instances. An overdose of acetaminophen in a chronic alcohol abuser may result in
      more severe hepatotoxicity than in the nonalcoholic. CYP2E1 and glutathione must
      be evaluated simultaneously rather than in isolation. Glucuronidation capacity in
      humans is not a factor except in massively overdosed patients.

PMID- 15239080
TI  - Management of hepatorenal syndrome: another piece of the puzzle.

PMID- 15239081
TI  - Liver injury in the setting of steatosis: crosstalk between adipokine and
      cytokine.

PMID- 15239082
TI  - Acetaminophen hepatoxicity: what do we know, what don't we know, and what do we
      do next?

PMID- 15239083
TI  - Characterization of mutations in ATP8B1 associated with hereditary cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent
      intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders.
      PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC
      patients experience intermittent attacks of cholestasis that resolve
      spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC.
      We report the genomic organization of ATP8B1 and mutation analyses of 180
      families with PFIC or BRIC that identified 54 distinct disease mutations,
      including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11
      small insertion or deletion mutations predicted to induce frameshifts, 1 large
      genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most
      mutations are rare, occurring in 1-3 families, or are limited to specific
      populations. Many patients are compound heterozygous for 2 mutations. Mutation
      type or location correlates overall with clinical severity: missense mutations
      are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and
      large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some
      mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even
      no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively,
      of the PFIC and BRIC patients screened.

PMID- 15239084
TI  - Cost-minimization analysis of MRC versus ERCP for the diagnosis of primary
      sclerosing cholangitis.
AB  - Investigations examining the use of magnetic resonance cholangiography (MRC) for
      the diagnosis of primary sclerosing cholangitis (PSC) have described comparable
      accuracy when compared to endoscopic retrograde cholangiopancreatography (ERCP).
      The effectiveness of MRC based on overall cost, however, remains unknown. Our aim
      was to determine the average cost per correct diagnosis using MRC or ERCP as the
      initial testing strategy for the diagnosis of PSC. A decision analysis model was
      constructed employing diagnostic test parameters prospectively determined among
      73 patients with clinically suspected biliary disease. ERCP was performed within
      24 hours after MRC. Cost data were derived from average Medicare reimbursement
      fee schedules. The prevalence of PSC in the study cohort was 32%. The sensitivity
      and specificity of MRC for the diagnosis of PSC were 82% and 98%, respectively.
      The average cost per correct diagnosis of PSC was 724.00 US dollars for initial
      MRC (including the cost of ERCP following a negative MRC examination) versus
      793.17 US dollars for initial ERCP. In the absence of biliary obstruction, the
      average cost per correct diagnosis of PSC was 549.64 US dollars with MRC versus
      623.25 US dollars or ERCP. The average cost of managing post-ERCP-related
      complications among patients with PSC was 2902.20 US dollars (range, 1915.40
      5031.54 US dollars). For ERCP to be the optimal initial test strategy, a
      prevalence rate of PSC greater than 45%, MRC specificity less than 85%, or
      reduction in the average cost per diagnosis to 538.30 US dollars would be
      required. In conclusion, MRC has comparable accuracy to ERCP and results in cost
      savings when used as the initial test strategy for diagnosing PSC.

PMID- 15239085
TI  - Beyond insulin resistance in NASH: TNF-alpha or adiponectin?
AB  - Adiponectin has antilipogenic and anti-inflammatory effects, while tumor necrosis
      factor alpha (TNF-alpha) reduces insulin sensitivity and has proinflammatory
      effects. We examined (1) the extent to which hypoadiponectinemia and TNF-alpha
      activation are features of nonalcoholic steatohepatitis (NASH) and (2) whether
      serum levels of these markers correlate with the severity of histological changes
      in 109 subjects with nonalcoholic fatty liver disease (NAFLD), including 80 with
      NASH and 29 with simple steatosis. By multivariate analysis, subjects with NASH
      had reduced adiponectin level and increased TNF-alpha and soluble TNF receptor 2
      (sTNFR2)-but not leptin levels, compared with controls matched by age, sex, and
      body mass index; these differences were independent of the increased insulin
      resistance (by homeostasis model [HOMA-IR]) in NASH. When compared with simple
      steatosis, NASH was associated with lower adiponectin levels and higher HOMA-IR,
      but there were no significant differences in the levels of TNF-alpha and sTNFR2.
      The majority of subjects with steatohepatitis (77%) had adiponectin levels less
      than 10 microg/mL and HOMA-IR greater than 3 units, but only 33% of those with
      pure steatosis had these findings. HOMA-IR and low serum adiponectin were also
      independently associated with increased grades of hepatic necroinflammation. In
      conclusion, hypoadiponectinemia is a feature of NASH independent of insulin
      resistance. Reduced adiponectin level is associated with more extensive
      necroinflammation and may contribute to the development of necroinflammatory
      forms of NAFLD.

PMID- 15239086
TI  - Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and
      type 1 hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is a functional renal disorder complicating
      decompensated cirrhosis. Treatments to date, except liver transplantation, have
      been able to improve but not normalize renal function. The aim of this study was
      to determine the efficacy of transjugular intrahepatic portosystemic stent shunt
      (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following
      improvement in systemic hemodynamics with a combination of midodrine, octreotide,
      and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1
      HRS received medical therapy until their serum creatinine reached below 135
      micromol/L for at least 3 days, followed by a TIPS if there were no
      contraindications. Patients were assessed before and after medical treatment, as
      well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of renal
      function, sodium handling, systemic hemodynamics, central blood volume, and
      hormonal markers. Medical therapy for 14 +/- 3 days improved renal function
      (serum creatinine: 233 +/- 29 micromol/L vs. 112 +/- 8 micromol/L, P =.001) and
      renal sodium excretion (5 +/- 2 mmol/d vs. 9 +/- 2 mmol/d, P =.002) in 10 of the
      14 patients. TIPS insertion in five of the responders further improved renal
      function and sodium excretion, so that by 12 months post-TIPS, glomerular
      filtration rate (96 +/- 20 mL/min, P <.01 vs. pre-TIPS) and urinary sodium
      excretion (119 +/- 15 mmol/d, P <.01 vs. pre-TIPS) were normal, associated with
      normalization of plasma renin and aldosterone levels and elimination of ascites.
      In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients
      with cirrhosis and ascites, following the improvement of renal function with
      combination therapy of midodrine, octreotide, and albumin.

PMID- 15239087
TI  - Ligation versus propranolol for the primary prophylaxis of variceal bleeding in
      cirrhosis.
AB  - In this randomized controlled multicenter trial, we compared endoscopic variceal
      banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal
      bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal
      varices (diameter >5 mm) without prior bleeding were randomized to VBL (n = 75)
      or PPL (n = 77). The groups were well matched with respect to baseline
      characteristics (age 56 +/- 10 years, alcoholic etiology 51%, Child-Pugh score
      7.2 +/- 1.8). The mean follow-up was 34 +/- 19 months. Data were analyzed on an
      intention-to-treat basis. Neither bleeding incidence nor mortality differed
      significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL
      group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years
      were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10%
      (PPL). It was associated with the ligation procedure in 2 patients (2.6%).
      Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks
      being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16%
      due to side effects. In conclusion, VBL and PPL were similarly effective for
      primary prophylaxis of variceal bleeding. VBL should be offered to patients who
      are not candidates for long-term PPL treatment.

PMID- 15239088
TI  - Regional differences in cerebral blood flow and cerebral ammonia metabolism in
      patients with cirrhosis.
AB  - Clinical and histopathological findings hint at regional differences in the
      brain's sensitivity to metabolic changes in cirrhosis. The aim of the present
      study was to examine regional differences in cerebral ammonia metabolism in
      patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). (13)N
      ammonia, (15)O-water positron emission tomography (PET) and magnetic resonance
      imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF)
      and the initial cerebral ammonia uptake rate (K1) were derived for several
      regions of interest from images of the desired parameters after interactive
      coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min),
      and the ammonia extraction fraction (K1/CBF) showed marked regional variance with
      the highest levels in the thalamus, the lenticular nucleus, and the cerebellum.
      In conclusion, the regional differences in cerebral ammonia uptake correspond to
      the distribution of histopathological changes in the brain of patients with
      cirrhosis as well as clinical features of HE, characterized by signs of basal
      ganglia and cerebellar dysfunction with corresponding signs of functional
      impairment, especially of the frontal cortex and cingulate gyrus.

PMID- 15239089
TI  - Hepatocellular telomere shortening correlates with chromosomal instability and
      the development of human hepatoma.
AB  - The telomere hypothesis of cancer initiation indicates that telomere shortening
      initiates cancer by induction of chromosomal instability. To test whether this
      hypothesis applies to human hepatocellular carcinoma (HCC), we analyzed the
      telomere length of hepatocytes in cytological smears of fine-needle biopsies of
      liver tumors from patients with cirrhosis (n = 39). The tumors consisted of 24
      HCC and 15 regenerative nodules as diagnosed by combined histological and
      cytological diagnostics. In addition, we analyzed the telomere length of
      hepatocytes in HCC and surrounding noncancerous liver tissue within individual
      patients in another cohort of 10 patients with cirrhosis. Telomere length
      analysis of hepatocytes was correlated with tumor pathology and ploidy grade of
      the tumors, which was analyzed by cytophotometry. Telomeres were significantly
      shortened in hepatocytes of HCC compared to hepatocytes in regenerative nodules
      or surrounding noncancerous liver tissue. Hepatocyte telomere shortening in HCC
      was independent of the patient's age. There was no overlap in mean telomere
      lengths of individual samples when comparing HCC with regenerative nodules or
      noncancerous surrounding liver. Within the HCC group, telomeres were
      significantly shorter in hepatocytes of aneuploid tumors compared to diploid
      tumors. In conclusion, our data suggest that the telomere hypothesis of cancer
      initiation applies to human HCC and that cell type-specific telomere length
      analysis might indicate the risk of HCC development.

PMID- 15239090
TI  - Effects of antiviral therapy on the cellular immune response in acute hepatitis
      C.
AB  - Spontaneous recovery occurs in a minority of patients with acute hepatitis C but
      is associated with vigorous and long-lasting cellular immune responses. Treatment
      induced recovery can be achieved in the majority of patients who are treated in
      the acute phase, but the kinetics and mechanisms of viral clearance and immune
      responsiveness are not known. Both direct antiviral effects and indirect immune
      mediated effects, such as immune modulation of Th2 to Th1 responses and
      prevention of exhaustion of cellular responses by rapid reduction of viral titer,
      have been proposed. To investigate how early antiviral therapy affects hepatitis
      C virus (HCV)-specific T cell responses, we performed detailed prospective
      clinical, virological, and immunological studies on 7 patients with acute
      hepatitis C who received antiviral therapy and were followed at 2 to 4 week
      intervals for 1 to 2 years. The total CD4(+) and CD8(+) cell response was
      analyzed with 600 overlapping HCV peptides and 6 proteins by ex vivo enzyme
      linked immunospot (ELISpot), intracellular cytokine staining, and proliferation
      assays. In contrast to earlier studies with selected HCV epitopes, this extended
      analysis detected multispecific interferon gamma(+) (IFN-gamma(+)) responses in
      each patient, even in the absence of T-cell proliferation. After initiation of
      antiviral therapy (at a mean of 20 weeks after infection), all sustained
      responders demonstrated gradually decreasing, then nearly absent HCV-specific T
      cell responses, whereas the sole patient who developed viral breakthrough after
      initial HCV control maintained cellular immune responses. In conclusion, a
      sustained response to antiviral therapy was not associated with a lasting
      enhancement of HCV-specific T-cell responsiveness in the blood.

PMID- 15239091
TI  - Long-term follow-up after successful interferon therapy of acute hepatitis C.
AB  - Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-alpha
      2b) prevents chronicity in almost all patients. So far, no data are available on
      the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The
      aim of this study was to assess the clinical, virological, and immunological long
      term outcome of 31 successfully treated patients with acute hepatitis C infection
      who were followed for a median of 135 weeks (52-224 weeks) after end of therapy.
      None of the individuals had clinical evidence of liver disease. Alanine
      aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C
      virus (HCV) RNA was negative throughout follow-up, even when investigated with
      the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5
      10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear
      cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as
      determined by the SF-36 questionnaire did not differ from the German reference
      control cohort. Ex vivo interferon gamma (IFN-gamma) ELISPOT analysis detected
      HCV-specific CD4(+) T-helper cell reactivity in only 35% of cases, whereas HCV
      specific CD8(+) T-cell responses were found in 4 of 5 HLA-A2-positive
      individuals. Anti-HCV antibody levels decreased significantly during and after
      therapy in all individuals. In conclusion, early treatment of symptomatic acute
      hepatitis C with IFN-alpha-2b leads to a long-term virological, biochemical, and
      clinical response. Waning of anti-HCV humoral immunity and presence of HCV
      specific CD8(+) (but not CD4(+)) T cells highlights the complexity of T-cell and
      B-cell memory to HCV, which might be significantly altered by IFN treatment.

PMID- 15239092
TI  - Distinct MHC class I and II alleles are associated with hepatitis C viral
      clearance, originating from a single source.
AB  - The role of cytotoxic T lymphocyte responses, restricted by human leukocyte
      antigen (HLA) class I alleles, is recognized as highly significant in the
      successful clearance of hepatitis C virus (HCV). The frequency of class I alleles
      in females inoculated with HCV genotype 1b from a single source was examined for
      an association with outcome. Class I typing was performed using polymerase chain
      reaction sequence-specific primers in 227 female subjects: 141 had chronic
      infection and 86 had viral clearance. Statistical analysis included chi(2)
      testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred
      more frequently in those with viral clearance (39.5%, 14%, and 9.3%,
      respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%,
      respectively; P < or = .005). B*08 occurred more often in those with chronic
      infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In
      combination with previously reported class II allele associations, over 75% that
      successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with
      only 37% of those with chronic infection (P <.0001). The haplotypes A*03-B*07
      DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501 are associated with
      viral clearance (P =.004 and.01, respectively). By multiple logistic regression
      analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with
      viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99).
      The haplotype A*01-B*08-Cw*07-DRB1*03011-DQB1*0201 is associated with chronic
      infection (P =.002), being independent for DQB1*0201 (OR 0.27). In conclusion,
      certain class I alleles are associated with outcome in this homogeneous cohort.
      More significantly, either HLA-A*03, -DRB1*0101, or -*0401 are carried by an
      overwhelming majority of those subjects who successfully clear HCV.

PMID- 15239093
TI  - Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV
      coinfection.
AB  - We examined the association of hepatitis C virus (HCV) infection with diabetes in
      veterans infected with human immunodeficiency virus (HIV) before and after the
      institution of highly active antiretroviral therapy (HAART). The role of age,
      race, liver disease, alcohol, and drug diagnoses upon the risk of diabetes was
      also determined. Male veterans with HIV who entered care between 1992 and 2001
      were identified from the Veterans Affairs (VA) administrative database.
      Demographic and disease data were extracted. Kaplan-Meier curves were plotted to
      determine the incidence of diabetes. Unadjusted and adjusted hazards ratios for
      diabetes were determined using Cox regression method. A total of 26,988 veterans
      were studied. In multivariate Cox regression analysis, factors associated with a
      diagnosis of diabetes included increasing age (HR, 1.44 per 10-year increase in
      age; 95% CI, 1.39-1.49), minority race (African American: HR, 1.35; 95% CI, 1.24
      1.48; Hispanic: HR, 1.63; 95% CI, 1.43-1.86), and care in the HAART era (HR,
      2.35; 95% CI, 2.01-2.75). There was a significant interaction between care in the
      HAART era and HCV infection, with HCV infection being associated with a
      significant risk of diabetes in the HAART era (HR, 1.39; 95% CI, 1.27-1.53) but
      not in the pre-HAART era (HR, 1.01; 95% CI, 0.75-1.36). In conclusion, HIV
      infected veterans in the HAART era are at a higher risk for diabetes compared
      with those in the pre-HAART era. HCV coinfection is associated with a
      significantly higher risk of diabetes in the HAART era, but not in the pre-HAART
      era. HCV-HIV coinfected patients should be aggressively screened for diabetes.

PMID- 15239094
TI  - A prospective controlled study of interferon-based therapy of chronic hepatitis C
      in patients on methadone maintenance.
AB  - We examined the feasibility of hepatitis C treatment in patients on opioid
      maintenance. One hundred patients with chronic hepatitis C, 50 on methadone
      maintenance, and 50 with no intravenous drug use or opioid maintenance for at
      least 5 years were prospectively matched for sex, age, hepatitis C virus (HCV)
      genotype and HCV RNA. The primary end point was undetectable HCV RNA at 24 weeks
      posttreatment. Treatment with peginterferon alfa-2b (1.5 microg/kg per week) and
      ribavirin (1000-1200 mg /day) was initiated for 24 weeks (HCV genotype 2, 3) or
      48 weeks (HCV genotype 1, 4). Within the first 8 weeks of therapy,
      discontinuation due to noncompliance or patient request was observed in 22%
      (11/50) in the methadone group versus 4% (2/50) in the control group (P =.02).
      After 8 weeks, there was no significant difference in discontinuation due to
      noncompliance or patient request (4/39 [10%] vs. 4/48 [8%]). There was no
      difference in discontinuation of therapy because of viral failure or adverse
      events (10/50 methadone vs. 6/50 control, P =.41). At the end of treatment, 50%
      (25/50) in the methadone group and 76% (38/50) in the control group had
      undetectable HCV RNA (P =.01). Sustained viral response was 42% (21/50) in the
      methadone group and 56% (28/50) in the control group (P =.16). No serious
      psychiatric event occurred in either group. In conclusion, peginterferon and
      ribavirin seem reasonably safe and sufficiently effective in patients on
      methadone maintenance. Patients discontinuing therapy due to noncompliance or
      request did so early, thereby limiting the cost of an unsuccessful approach to
      treatment.

PMID- 15239095
TI  - Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV.
AB  - Persons with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      coinfection are at increased risk for progression to cirrhosis compared with
      persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the
      mechanism of liver injury is presumed to be due to HCV-specific T cell
      destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have
      higher rates of fibrosis progression. We examined intrahepatic cellular immune
      responses to HCV antigens to determine whether there were qualitative or
      quantitative differences in subjects with and without HIV. Expanded, CD4
      enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12
      subjects with HIV/HCV were cultured in the presence of HCV core protein,
      nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and
      Candida. Secretion of interferon gamma (IFN-gamma), tumor necrosis factor alpha
      (TNF-alpha), and interleukin (IL) 10 was determined using enzyme-linked
      immunosorbent spot assay. There were no significant differences in liver biopsy
      grade or stage for HIV/HCV versus HCV groups. There were no significant
      differences between groups in the secretion of IFN-gamma or TNF-alpha in response
      to HCV or recall antigens. However, there was a significant increase in IL-10
      secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and
      HCV coinfection. In conclusion, subjects with coinfection have an alteration of
      intrahepatic HCV-specific IL-10 cytokine response that may have implications for
      HCV-related disease progression.

PMID- 15239096
TI  - Usefulness of dried blood samples for quantification and molecular
      characterization of HBV-DNA.
AB  - The purpose of this study was to assess the use of dried blood spot (DBS) samples
      for hepatitis B virus (HBV) DNA quantification, HBV genotyping, and detection of
      G1896A precore mutants and variants in the YMDD polymerase motif. We studied DBS
      and serum samples from 82 patients with chronic HBV infection (23 hepatitis B e
      antigen [HBeAg]-positive and 39 HBeAg-negative), 20 HBeAg-inactive carriers, and
      15 HBeAg-negative patients under lamivudine therapy (selected from chronic HBV
      patients). DBS samples consisted of approximately 20 microL of blood applied to 5
      mm paper disks. HBV DNA quantification and HBV precore mutant detection were done
      using real-time polymerase chain reaction, HBV genotyping using restriction
      fragment length polymorphism, and YMDD variant detection by Inno-lipa assay. DBS
      and serum results were compared. HBV DNA was detected in a range of 10(2)-10(8)
      copies/mL, with low intra-assay and inter-assay variation (<10%). Median DBS HBV
      DNA (copies/mL) was: 3.7 x 10(6) in HBeAg-positive, 6.2 x 10(5) in HBeAg
      negative, and 5.5 x 10(2) in inactive carriers (P <.05). HBV DNA was positive in
      serum (median 5 x 10(3) copies/mL) but negative in DBS for five inactive
      carriers. The correlation coefficient between HBV DNA concentration in DBS versus
      serum samples was r(2) = 0.96 (P <.001). The sensitivity of HBV DNA detection in
      DBS samples was 1 log(10) lower than in serum samples. Concordance between DBS
      and serum for HBV genotyping, and for precore mutant and YMDD variant detection
      was optimal. DBS storage for 7 days at room temperature and 21 days at -20
      degrees C revealed no decrease in HBV DNA levels or integrity. In conclusion, the
      DBS sample is useful for HBV DNA quantification, genotyping, and detection of
      precore mutant and YMDD variants. All four determinations can be completed with a
      single drop of dried blood.

PMID- 15239097
TI  - A phase II dose-escalating trial of clevudine in patients with chronic hepatitis
      B.
AB  - Current therapies available for the treatment of chronic hepatitis B are limited
      in their ability to result in a cure. Clevudine is a new pyrimidine analog with
      potent anti-hepatitis B virus (HBV) activity in vitro. A multicenter dose
      escalation study evaluated clevudine at 10, 50, 100, and 200 mg once daily for 28
      days. Eligible patients had HBV DNA levels of 3 x 10(6) copies/mL or more, had
      not undergone nucleoside treatment, and were without human immunodeficiency or
      hepatitis C virus coinfection. Thirty-two patients were enrolled (5, 10, 10, and
      7 patients in the 10-, 50-, 100-, and 200-mg dose groups, respectively), 81% were
      male, 81% Asian, and 88% were hepatitis Be antigen (HBeAg) positive at baseline.
      Median pretreatment serum HBV DNA levels ranged from 7.3 to 8.8 log(10)
      copies/mL. After 28 days, the median HBV DNA log(10) change from baseline was 
      2.5, -2.7, -3.0, and -2.6 log(10). Six months after dosing, median changes from
      baseline were -1.2, -1.4, -2.7 and -1.7 log(10) in the 10-, 50-, 100-, and 200-mg
      cohorts, respectively. Six of 27 patients lost HBeAg, and 3 of 27 patients
      seroconverted to HBe antibody. Clevudine was well tolerated, with no dose
      limiting toxicities. A transient increase in alanine aminotransferase of up to
      7.8 times the upper limit of normal (increase ranged from 20 to 186 IU/L) was
      observed in six patients in the 100-mg cohort, without signs of liver failure.
      These increases were associated with improved viral suppression. The
      pharmacokinetic profile of clevudine was proportional to the dose. In conclusion,
      these results demonstrate the tolerability and potent activity of clevudine in
      HBV-infected patients and support further clinical study.

PMID- 15239098
TI  - Bile acid-induced negative feedback regulation of the human ileal bile acid
      transporter.
AB  - Ileal expression of the apical sodium-dependent bile acid transporter (ASBT) in
      the rat is unaffected by bile salts, yet in the mouse it is under negative
      feedback regulation. The bile acid responsiveness of human ASBT is unknown. The
      human ASBT promoter linked to a luciferase reporter was studied in Caco-2 cells
      treated with chenodeoxycholic acid (CDCA) and transfected with expression
      plasmids for farnesoid X-receptor (FXR), short heterodimer partner (SHP), and
      retinoic acid receptor/retinoid X receptor (RAR/RXR). CDCA treatment of Caco-2
      cells led to a 75% reduction in steady-state ASBT messenger RNA levels and a 78%
      reduction in human ASBT promoter activity. A dominant negative FXR abrogated the
      response to CDCA. Site-directed mutagenesis of an RAR/RXR cis element in the
      human ASBT promoter reduced its activity by 50% and eliminated the bile acid
      response. Retinoic acid activated the human ASBT promoter fourfold. SHP repressed
      the activity of the ASBT promoter and reduced activation by retinoic acid.
      Antisense mediated knock-down of SHP in Caco-2 cells partially offset the bile
      acid mediated repression of ASBT promoter activity. In conclusion, the human ASBT
      is positively regulated by retinoic acid. Bile acids induce a negative feedback
      regulation of human ASBT via an FXR-mediated, SHP-dependent effect upon RAR/RXR
      activation of ASBT.

PMID- 15239099
TI  - Mitochondrial nitric oxide synthase drives redox signals for proliferation and
      quiescence in rat liver development.
AB  - Mitochondrial nitric oxide synthase (mtNOS) is a fine regulator of oxygen uptake
      and reactive oxygen species that eventually modulates the activity of regulatory
      proteins and cell cycle progression. From this perspective, we examined liver
      mtNOS modulation and mitochondrial redox changes in developing rats from
      embryonic days 17-19 and postnatal day 2 (proliferating hepatocyte phenotype)
      through postnatal days 15-90 (quiescent phenotype). mtNOS expression and activity
      were almost undetectable in fetal liver, and progressively increased after birth
      by tenfold up to adult stage. NO-dependent mitochondrial hydrogen peroxide
      (H(2)O(2)) production and Mn-superoxide dismutase followed the developmental
      modulation of mtNOS and contributed to parallel variations of cytosolic H(2)O(2)
      concentration ([H(2)O(2)](ss)) and cell fluorescence. mtNOS-dependent
      [H(2)O(2)](ss) was a good predictor of extracellular signal-regulated kinase
      (ERK)/p38 activity ratio, cyclin D1, and tissue proliferation. At low 10(-11)-10(
      12) M [H(2)O(2)](ss), proliferating phenotypes had high cyclin D1 and phospho
      ERK1/2 and low phospho-p38 mitogen-activated protein kinase, while at 10(-9) M
      [H(2)O(2)](ss), quiescent phenotypes had the opposite pattern. Accordingly,
      leading postnatal day 2-isolated hepatocytes to embryo or adult redox conditions
      with H(2)O(2) or NO-H(2)O(2) scavengers, or with ERK inhibitor U0126, p38
      inhibitor SB202190 or p38 activator anisomycin resulted in correlative changes of
      ERK/p38 activity ratio, cyclin D1 expression, and [(3)H] thymidine incorporation
      in the cells. Accordingly, p38 inhibitor SB202190 or N-acetyl-cysteine prevented
      H(2)O(2) inhibitory effects on proliferation. In conclusion, the results suggest
      that a synchronized increase of mtNOS and derived H(2)O(2) operate on hepatocyte
      signaling pathways to support the liver developmental transition from
      proliferation to quiescence.

PMID- 15239100
TI  - Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene
      of beta-catenin in the liver.
AB  - To clarify molecular mechanisms underlying liver carcinogenesis induced by
      aberrant activation of Wnt pathway, we isolated the target genes of beta-catenin
      from mice exhibiting constitutive activated beta-catenin in the liver. Adenovirus
      mediated expression of oncogenic beta-catenin was used to isolate early targets
      of beta-catenin in the liver. Suppression subtractive hybridization was used to
      identify the leukocyte cell-derived chemotaxin 2 (LECT2) gene as a direct target
      of beta-catenin. Northern blot and immunohistochemical analyses demonstrated that
      LECT2 expression is specifically induced in different mouse models that express
      activated beta-catenin in the liver. LECT2 expression was not activated in livers
      in which hepatocyte proliferation was induced by a beta-catenin-independent
      signal. We characterized by mutagenesis the LEF/TCF site, which is crucial for
      LECT2 activation by beta-catenin. We further characterized the chemotactic
      property of LECT2 for human neutrophils. Finally, we have shown an up-regulation
      of LECT2 in human liver tumors that expressed aberrant activation of beta-catenin
      signaling; these tumors constituted a subset of hepatocellular carcinomas (HCC)
      and most of the hepatoblastomas that were studied. In conclusion, our results
      show that LECT2, which encodes a protein with chemotactic properties for human
      neutrophils, is a direct target gene of Wnt/beta-catenin signaling in the liver.
      Since HCC develops mainly in patients with chronic hepatitis or cirrhosis induced
      by viral or inflammatory factors, understanding the role of LECT2 in liver
      carcinogenesis is of interest and may lead to new therapeutic perspectives.

PMID- 15239101
TI  - Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in
      KK-Ay obese mice.
AB  - Adiponectin, an adipocytokine, has been identified in adipose tissue, and its
      receptors are widely distributed in many tissues, including the liver. The
      present study was performed to clarify the role of adiponectin in
      lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed
      the effects of adiponectin pretreatment on liver injury induced by D
      galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced
      significant increases in aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in
      hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver
      injury was more pronounced in KK-Ay obese mice than in lean controls.
      Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum
      AST and ALT levels and the apoptotic and necrotic changes in hepatocytes,
      resulting in a reduction in lethality. In addition, pretreatment with adiponectin
      attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis
      factor alpha (TNF-alpha) levels and increased peroxisome proliferator-activated
      receptor (PPAR) alpha messenger RNA expression in the liver. Furthermore,
      abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro
      exhibited decreased LPS-induced TNF-alpha production compared with controls.
      Finally, adiponectin pretreatment also ameliorated TNF-alpha-induced liver
      injury. In conclusion, these findings suggest that adiponectin prevents LPS
      induced hepatic injury by inhibiting the synthesis and/or release of TNF-alpha of
      KK-Ay obese mice.

PMID- 15239102
TI  - Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression
      via a lysosomal pathway.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although
      NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly
      understood. The aim of this study was to examine the cellular mechanisms involved
      in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver
      cells resulted in Bax translocation to lysosomes and lysosomal destabilization
      with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the
      cytosol. This process was also partially dependent on ctsb. Lysosomal
      destabilization resulted in nuclear factor kappa B-dependent tumor necrosis
      factor alpha expression. Release of ctsb into the cytoplasm was also observed in
      humans with NAFLD and correlated with disease severity. In a dietary murine model
      of NAFLD, either genetic or pharmacological inactivation of ctsb protected
      against development of hepatic steatosis, liver injury, and insulin resistance
      with its associated "dysmetabolic syndrome." In conclusion, these data support a
      lipotoxic model of FFA-mediated lysosomal destabilization.

PMID- 15239103
TI  - Liposome-mediated extracellular superoxide dismutase gene delivery protects
      against acute liver injury in mice.
AB  - Our previous study demonstrated that polycationic liposomes are highly stable in
      the bloodstream and represent an effective agent for liver gene delivery. We
      report here that liposome-mediated extracellular superoxide dismutase (EC-SOD)
      gene delivery successfully prevented acute liver injury in mice. The therapeutic
      efficacy of EC-SOD gene delivery by polycationic liposomes was determined against
      the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in
      a mouse model of acute liver injury caused by D-galactosamine and
      lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD
      plasmid led to a striking increase in superoxide dismutase activity in the
      medium. The transfected cells had much less cell death after reactive oxygen
      species exposure compared with untransfected or control plasmid-transfected
      cells. In a model of acute liver injury, serum alanine aminotransferase levels in
      mice receiving portal vein injections of EC-SOD lipoplexes were much lower than
      in those receiving normal saline, liposomes alone, or control lipoplexes. Liver
      histology confirmed that there was less cell death in the EC-SOD lipoplex-treated
      group. Quantitative reverse transcriptase polymerase chain reaction showed a 55
      fold increase in human EC-SOD gene expression in the liver of mice injected with
      EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated
      mice was higher than in the control groups; this was associated with higher liver
      glutathione levels and reduced lipid peroxidation. In conclusion, polycationic
      liposome-mediated EC-SOD gene delivery protects against reactive oxygen species
      toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D
      galactosamine-sensitized mice.

PMID- 15239104
TI  - Connexin 32 dominant-negative mutant transgenic rats are resistant to hepatic
      damage by chemicals.
AB  - Connexins are subunits of gap junction channels, which allow direct transfer of
      ions, secondary messenger molecules, and other metabolites between contacting
      cells. Gap junctions are believed to be involved in tissue homeostasis, embryonic
      development, and control of cell proliferation. Several studies have shown that
      cell damage signals are transmitted through gap junctions when cells are
      irradiated or when cells bearing the herpes simplex virus-thymidine kinase (HSV
      TK) gene are treated with ganciclovir. We established 2 lines of transgenic rats
      with a dominant-negative mutant of connexin 32 gene under control of the albumin
      promoter. In the livers of transgenic rats, membrane localization of normal
      endogenous connexin 32 protein is disturbed, and gap junction capacity measured
      by scrape dye-transfer assay in vivo is markedly decreased when compared with
      wild-type rats. The present investigation concerned susceptibility to the liver
      toxic substances D-galactosamine and carbon tetrachloride. These toxicants
      induced massive liver cell death and elevated serum alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) levels in the wild-type rats; however,
      much fewer liver cells were damaged and serum enzyme elevation was much lower in
      the transgenic rats. In conclusion, gap junctional intercellular communication
      (GJIC) plays an important role in toxic effects of chemicals; damage or death
      signals may pass through gap junctions in the rat liver in vivo.

PMID- 15239105
TI  - Hypertonic preconditioning prevents hepatocellular injury following
      ischemia/reperfusion in mice: a role for interleukin 10.
AB  - Ischemia/reperfusion (I/R) of the liver occurs in many clinical scenarios
      including trauma, elective surgery, and transplantation. Events initiated by this
      process can lead to inflammation in the liver, culminating in local injury as
      well as distant organ dysfunction. Recent studies have suggested that hypertonic
      saline exerts anti-inflammatory effects, which may be beneficial in preventing
      organ injury. In the present study, we examine the effect of hypertonic saline on
      the development of liver inflammation following I/R in both rat and mouse models.
      Hypertonic pretreatment was shown to prevent liver enzyme release concomitant
      with a reduction in liver neutrophil sequestration. Hypertonic saline appeared to
      exert this effect by inhibiting liver tumor necrosis factor alpha (TNF-alpha)
      generation, an effect that culminated in reduced liver adhesion molecule
      expression. Hypertonic saline pretreatment was shown to augment liver interleukin
      10 (IL-10) expression following I/R, as a potential mechanism underlying its anti
      inflammatory effect. To examine the role of IL-10 in the protective effect of
      hypertonic saline on liver I/R injury, we used a murine model of I/R. In wild
      type mice, hypertonic pretreatment similarly prevented liver injury induced by
      I/R. However, in IL-10 knockout animals, hypertonic pretreatment was unable to
      prevent the liver enzyme release, TNF-alpha generation, or neutrophil
      sequestration induced by I/R. In conclusion, these findings define a novel
      mechanism responsible for the anti-inflammatory effects of hypertonic saline and
      also suggest a potential clinical role for hyperosmolar solutions in the
      prevention of liver injury associated with I/R.

PMID- 15239106
TI  - S-adenosylmethionine and its metabolite induce apoptosis in HepG2 cells: Role of
      protein phosphatase 1 and Bcl-x(S).
AB  - S-adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) are
      proapoptotic in HepG2 cells. In microarray studies, we found SAMe treatment
      induced Bcl-x expression. Bcl-x is alternatively spliced to produce two distinct
      mRNAs and proteins, Bcl-x(L) and Bcl-x(S). Bcl-x(L) is antiapoptotic, while Bcl
      x(S) is proapoptotic. In this study we showed that SAMe and MTA selectively
      induced Bcl-x(S) in a time- and dose-dependent manner in HepG2 cells. There are
      three transcription start sites in the human Bcl-x gene which yield only Bcl-x(L)
      in control HepG2 cells. SAMe and MTA treatment did not affect promoter usage, but
      while one promoter yielded only Bcl-x(L), the other two yielded both Bcl-x(L) and
      Bcl-x(S), with Bcl-x(S) as the predominant messenger RNA (mRNA) species.
      Trichostatin A, 3-deaza-adenosine, cycloleucine, and okadaic acid had no effect
      on Bcl-x(S) induction by SAMe or MTA. Calyculin A and tautomycin, on the other
      hand, blocked SAMe and MTA-mediated Bcl-x(S) induction and apoptosis in a dose
      dependent manner. SAMe and MTA increased protein phosphatase 1 (PP1) catalytic
      subunit mRNA and protein levels and dephosphorylation of serine-arginine
      proteins, with the latter blocked by calyculin A. The effects of SAMe and MTA on
      Bcl-x(S), PP1 expression, and apoptosis were also seen in 293 cells, but not in
      primary hepatocytes. Induction of Bcl-x(S) by ceramide in HepG2 cells also
      resulted in apoptosis. In conclusion, we have uncovered a highly novel action of
      SAMe and MTA, namely the ability to affect the cellular phosphorylation state and
      alternative splicing of genes, in this case resulting in the induction of Bcl
      x(S) leading to apoptosis.

PMID- 15239107
TI  - Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells.
AB  - Gliotoxin has been shown to promote a reversal of liver fibrosis in an animal
      model of the disease although its mechanism of action in the liver is poorly
      defined. The effects of gliotoxin on activated hepatic stellate cells (HSCs) and
      hepatocytes have therefore been examined. Addition of gliotoxin (1.5 microM) to
      culture-activated HSCs resulted in its rapid accumulation, resulting in increased
      levels of glutathione and apoptosis without any evidence of oxidative stress. In
      contrast, although hepatocytes also rapidly sequestered gliotoxin, cell death
      only occurred at high (50-microM) concentrations of gliotoxin and by necrosis. At
      high concentrations, gliotoxin was metabolized by hepatocytes to a reduced
      (dithiol) metabolite and glutathione was rapidly oxidized. Fluorescent dye
      loading experiments showed that gliotoxin caused oxidative stress in hepatocytes.
      Antioxidants--but not thiol redox active compounds--inhibited both oxidative
      stress and necrosis in hepatocytes. In contrast, HSC apoptosis was not affected
      by antioxidants but was potently abrogated by thiol redox active compounds. The
      adenine nucleotide transporter (ANT) is implicated in mitochondrial-dependent
      apoptosis. HSCs expressed predominantly nonliver ANT isoform 1, and gliotoxin
      treatment resulted in a thiol redox-dependent alteration in ANT mobility in HSC
      extracts, but not hepatocyte extracts. In conclusion, these data suggest that
      gliotoxin stimulates the apoptosis of HSCs through a specific thiol redox
      dependent interaction with the ANT. Further understanding of this mechanism of
      cell death will aid in finding therapeutics that specifically stimulate HSC
      apoptosis in the liver, a promising approach to antifibrotic therapy.

PMID- 15239108
TI  - Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells
      via protein kinase A activation.
AB  - Hepatocellular carcinoma (HCC) is a common human malignancy. Its high mortality
      rate is mainly a result of high intrahepatic recurrence and portal venous
      invasion (PVI). We previously reported that the development of PVI is related to
      levels of des-gamma-carboxy prothrombin (DCP), a serum protein that increases at
      a notably higher rate in patients with HCC. Because DCP is produced by a vitamin
      K shortage, we examined the biological effects of extrinsic supplementation of
      vitamin K(2) in HCC cells in vitro and in vivo. Consequently, vitamin K(2)
      inhibits the growth and invasion of HCC cells through the activation of protein
      kinase A, which modulates the activities of several transcriptional factors and
      inhibits the small GTPase Rho, independent of suppression of DCP. In addition,
      administration of vitamin K(2) to nude mice inoculated with liver tumor cells
      reduced both tumor growth and body weight loss. In conclusion, similar to an
      acyclic retinoid--which was previously reported to prevent the recurrence of HCC-
      vitamin K(2), another lipid-soluble vitamin, may be a promising therapeutic means
      for the management of HCC.

PMID- 15239110
TI  - The nuclear bile acid receptor FXR as a novel therapeutic target in cholestatic
      liver diseases: hype or hope?

PMID- 15239109
TI  - Antiangiogenic property of pigment epithelium-derived factor in hepatocellular
      carcinoma.
AB  - Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous
      antiangiogenic reagents discovered to date. Its antiangiogenic potential in
      neoplastic disease remains unclear. In this study, we investigated antiangiogenic
      property of PEDF in hepatocellular carcinoma (HCC), a typical hypervascular
      tumor. In HCC cell lines, constitutive messenger RNA and protein expression of
      PEDF varied. Genomic DNA encoding the PEDF gene was the same in the cell lines
      examined by Southern blotting. In chemically induced hypoxic conditions, secreted
      PEDF protein was suppressed in contrast to elevation of vascular endothelial
      growth factor protein. When PEDF was overexpressed by gene transfer,
      proliferation and migration of endothelial cells were inhibited in conditioned
      media derived from all HCC cell lines. However, the serum concentration of PEDF,
      as measured by enzyme-linked immunosorbent assay, was decreased in patients with
      cirrhosis or HCC complicated by cirrhosis compared to healthy volunteers and
      patients with chronic hepatitis. According to the endothelial cell proliferation
      assay, the serum PEDF of patients with HCC had antiangiogenic activity. Moreover,
      intratumoral injection of a PEDF-expressing plasmid in athymic mouse models
      caused significant inhibition of preestablished tumor growth. In conclusion, PEDF
      plays a role in the angiogenic properties of HCC. Reduction of serum PEDF
      concentration associated with the development of chronic liver diseases may
      contribute to the progression of HCC. In addition, gene therapy using PEDF may
      provide an efficient treatment for HCC.

PMID- 15239111
TI  - "HOPE" for the liver? Mechanistic insight into the role of the renin-angiotensin
      system in hepatic fibrosis.

PMID- 15239112
TI  - HCV carriers with persistently normal aminotransferase levels.

PMID- 15239113
TI  - A forgotten population with chronic hepatitis C infection: subjects coinfected
      with hepatitis B virus.

PMID- 15239115
TI  - Corrections to the AASLD Practice Guideline.

PMID- 15239122
TI  - Effect of exposure to light-at-night on life span and spontaneous carcinogenesis
      in female CBA mice.
AB  - The effect of constant illumination on the development of spontaneous tumors in
      female CBA mice was investigated. Fifty female CBA mice starting from the age of
      2 months were kept under standard light/dark regimen (12 hr light:12 hr dark; LD)
      and 50 CBA mice of similar age were kept under constant illumination (24 hr a
      day, 2,500 Lux, LL). Exposure to the LL regimen decreased food consumption but
      did not influence body weight, significantly accelerated age-related disturbances
      in estrous function, and was followed by a significant increase in spontaneous
      tumor incidence in female CBA mice. Tumor incidence as well as the number of
      total or malignant tumors was significantly increased in the LL group compared to
      the LD group (p < 0.001). The incidence of lung adenocarcinomas, leukemias and
      hepatocarcinomas was 7/50; 6/50 and 4/50 in the LL group and 1/50; 0/50 and 0/50
      in the LD group. Mice from the LL groups had shorter life spans then those from
      the LD group. The data demonstrate, for the first time, that exposure to constant
      illumination was followed by increases in the incidence of spontaneous lung
      carcinoma, leukemias and hepatocarcinoma in female CBA mice.

PMID- 15239123
TI  - Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde
      concentration in saliva.
AB  - Alcohol drinking and smoking are independent risk factors for upper digestive
      tract cancers. Furthermore, their combined use interacts in a multiplicative way
      on cancer risk. There is convincing evidence that acetaldehyde, the first
      metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen
      in humans. Therefore, we examined the combined effect of alcohol drinking and
      tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers
      and 6 nonsmokers participated in the study. First, to measure the effect of
      alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of
      ethanol and saliva samples were collected every 20 min for 160 min thereafter.
      After a 3-day washout period, smokers ingested again the same amount of ethanol
      and smoked one cigarette every 20 min and saliva samples were collected at 10 min
      intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by
      headspace gas chromatograph. Firstly, smokers without concomitant smoking during
      ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations
      than nonsmokers after ethanol ingestion (AUC 114.8 +/- 11.5 vs. 54.2 +/- 8.7
      microM x hr, respectively; p = 0.002). Secondly, smokers with active smoking
      during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels
      than nonsmokers (AUC 369.5 +/- 12.2 vs. 54.2 +/- 8.7 microM x hr, respectively; p
      < 0.001). We conclude that this markedly increased exposure of upper digestive
      tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking
      subjects may explain the synergistic and multiplicative risk effect of alcohol
      drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis.

PMID- 15239124
TI  - Enhanced in vitro invasiveness and drug resistance with altered gene expression
      patterns in a human lung carcinoma cell line after pulse selection with
      anticancer drugs.
AB  - The human lung carcinoma cell line DLKP was exposed to sequential pulses of 10
      commonly used chemotherapeutic drugs (VP-16, vincristine, taxotere, mitoxantrone,
      5-fluorouracil, methotrexate, CCNU, BCNU, cisplatin and chlorambucil); resulting
      cell lines exhibited resistance to the selecting agents (ranging approx. 1.5- to
      36-fold) and, in some cases, cross-resistance to methotrexate (approx. 1.4- to 22
      fold), vincristine (1.6- to 262-fold), doxorubicin (Adriamycin, approx. 1.1- to
      33-fold) and taxotere (approx. 1.1- to 36-fold). Several of the variants
      displayed collateral sensitivity to cisplatin. A marked increase in in vitro
      invasiveness and motility was observed with variants pulsed with mitoxantrone, 5
      fluorouracil, methotrexate, BCNU, cisplatin and chlorambucil. There was no
      significant change in invasiveness of cells pulsed with VP-16, vincristine,
      taxotere or CCNU. All of the pulse-selected variants showed elevated levels of
      MDR-1/P-gp protein by Western blot analysis, although mdr-1 mRNA levels were not
      increased (except for DLKP-taxotere). In DLKP-taxotere, MRP1 protein levels were
      also greatly elevated, but mrp1 mRNA levels remained unchanged. BCRP was
      upregulated in DLKP-mitoxantrone at both the mRNA and protein levels. Gelatin
      zymography, Western blot and RT-PCR showed that DLKP and its variants secreted
      MMPs 2, 9 and 13. MMP inhibition assays suggested that MMP-2 plays a more
      important role than MMPs 9 and 13 in cell invasion of these DLKP drug-resistant
      variants in vitro. These results indicate that drug exposure may induce not only
      resistance but also invasiveness in cancer cells.

PMID- 15239125
TI  - Decreased expression of cytochrome P450 2E1 is associated with poor prognosis of
      hepatocellular carcinoma.
AB  - Cytochrome P450-2E1 (CYP2E1) is one of the major hepatic enzymes involved in the
      metabolism of procarcinogen. Our study aimed to investigate the differential
      expression level of CYP2E1 and its clinicopathological significance in
      hepatocellular carcinoma (HCC). CYP2E1 revealed low level of expression in 70% of
      the tumor tissues, when compared to the adjacent nontumor tissues, at both mRNA
      and protein levels. The low expression of CYP2E1 was significantly correlated
      with the aggressive tumor phenotype, including poor differentiation status (by
      the Edmondson grading system) (p=0.038), absence of tumor capsule (p=0.030) and
      younger age of the patients (p=0.002). Multivariate analysis indicated that
      CYP2E1 expression level and pTNM stage were independent prognostic factors for
      disease-free survival. CYP2E1 was also shown to have a differential expression
      level in different liver tissues. The level of CYP2E1 was significantly higher in
      nontumor tissues from HCC patients compared to the intermediate level in
      cirrhosis livers from noncancer patients and normal livers from healthy persons.
      Tumor tissues were shown to have the lowest expression level. In conclusion, our
      results have shown that CYP2E1 is upregulated in the nontumor tissue and
      downregulated in tumor tissue, which is associated with aggressive tumor type and
      poor prognosis of the patients. It suggested that the differential expression of
      CYP2E1 may play an important role in HCC tumorigenesis.

PMID- 15239126
TI  - Aberrant intracellular localization of SET-CAN fusion protein, associated with a
      leukemia, disorganizes nuclear export.
AB  - The SET-CAN fusion gene is the product of a chromosomal rearrangement found on
      9q34 associated with an acute undifferentiated leukemia. SET-CAN encodes an
      almost complete SET protein fused to the C-terminal two-thirds of CAN. SET is
      also known as TAF-Ibeta, a histone chaperone and intracellular inhibitor of
      protein phosphatase 2A, whereas CAN is identical to Nup214, a nucleoporin
      protein. To obtain insight into the leukemogenic function of SET/TAF-Ibeta
      CAN/Nup214, we have examined its subcellular localization. Immunofluorescence
      analyses showed that SET/TAF-Ibeta and CAN/Nup214 are found in the nucleus and
      the nuclear envelope, respectively, whereas the majority of SET/TAF-Ibeta
      CAN/Nup214 is localized in the nucleus. SET/TAF-Ibeta-CAN/Nup214 interacted with
      hCRM1, one of the nuclear export factors, and caused aberrant intracellular
      localization of hCRM1. In cells expressing SET/TAF-Ibeta-CAN/Nup214, a protein
      containing a nuclear export signal accumulated in the nucleus. The export of this
      protein was partially restored by overexpression of hCRM1. These results suggest
      that aberrantly localized molecules associated with SET/TAF-Ibeta-CAN/Nup214 may
      be involved in oncogenesis.

PMID- 15239127
TI  - Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the
      process of neuroendocrine differentiation.
AB  - In vitro, the human prostate cancer (PCA) cell line LNCaP can be permanently
      transdifferentiated into a quiescent neuroendocrine (NE) phenotype by the
      cytokine interleukin-6 (IL-6). Recently, we have shown that the growth of
      prostate cancer cells is significantly suppressed when cocultured with NE cells.
      In order to explore the inhibitory activity of IL-6 on prostate tumor growth,
      nude mice bearing xenografts of the PCA cell lines LNCaP and DU-145 (a line that
      is incapable of NE transdifferentiation by IL-6 in vitro) were treated with IL-6
      for 3 weeks, either injected around the tumor or systematically released from
      implanted minipumps. Both administration forms of IL-6 inhibited the growth of
      LNCaP xenografts by more than 75% compared to the control group. In contrast,
      there was no difference in DU-145 tumor growth between IL-6-treated animals and
      controls. In comparison to control and DU-145 tumors, both IL-6 injected and pump
      infused LNCaP tumors exhibited a significant increase in the expression of the NE
      markers neuron-specific enolase (NSE) and betaIII tubulin. Serum NSE levels were
      also significantly elevated in both IL-6-treated LNCaP tumor groups when compared
      to controls. IL-6 treatment resulted in G(0) cell cycle accumulation as evidenced
      by a loss of Ki-67 expression in > 90% of LNCaP tumor cells. These combined
      results demonstrate that IL-6-induced NE transdifferentiation of PCA cells has a
      significant inhibitory effect on tumor growth in mice. Agents, like IL-6, capable
      of NE transdifferentiation of PCA cells, should be considered as a new
      therapeutic approach for the treatment of prostate cancer.

PMID- 15239128
TI  - Peroxiredoxins, a novel protein family in lung cancer.
AB  - Cigarette smoke, the major risk factor for lung cancer, induces an accumulation
      of reactive oxygen species. These have multiple effects on cell defense, cell
      proliferation and cell death. Thus, compounds involved in the regulators of redox
      balance can be hypothesized to play a fundamental role in both carcinogenesis and
      tumor progression. Here, we have evaluated the expressions of all 6
      peroxiredoxins (Prxs I-VI) in lung carcinomas. Prxs represent a protein family
      with the capability of breaking down hydrogen peroxide; thus, they can
      participate in cellular antioxidant defense, regulate cell proliferation and
      increase drug resistance of cultured cells. Altogether 92 cases were investigated
      by immunohistochemistry, including 32 adenocarcinomas, 45 squamous cell, 9 small
      cell and 6 other carcinomas. Additionally, 11 cases with adenocarcinoma or
      squamous cell carcinoma were studied by Western analysis and/or by RT-PCR. Prxs
      I, II, IV and VI were particularly elevated in lung carcinomas as assessed by
      immunohistochemistry and/or RT-PCR. Western analysis revealed that Prxs I and IV
      were significantly elevated in tumors compared to nonmalignant tissue (p = 0.04
      and 0.002, respectively). There were remarkable variations in Prx expression in
      various tumor subtypes, the most striking being Prx IV expression, which was
      mainly associated with adenocarcinoma. Elevated Prx VI expression was associated
      with high-grade squamous cell carcinoma (p = 0.03) and Prx II expression, with
      advanced tumor stage (p = 0.01). Our results suggest that Prxs may have effects
      on the progression of lung cancer.

PMID- 15239129
TI  - Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T
      breast adenocarcinoma cells.
AB  - Caveolin-1 is a major caveolae-coat protein involved in a variety of cell
      signaling processes. Some studies have suggested that the level of caveolin-1
      expression positively correlates with multi-drug resistance in cancer cells. We
      demonstrated for the first time that Hs578T doxorubicin resistant cells
      (Hs578T/Doxo), which contain low levels of endogenous caveolin-1 and high levels
      of P-glycoprotein, are rendered drug-sensitive by overexpression of exogenous
      caveolin-1. MTT assays showed that after overexpressing caveolin-1, the drug
      resistance of Hs578T/Doxo cells to doxorubicin and cisplatin was reduced from
      25.4 +/- 1.5 and 65.3 +/- 2.5 microg/ml to 0.8 +/- 0.15 and 23.2 +/- 2.1
      microg/ml, respectively (i.e. reduced by 97% and 64%, respectively). Furthermore,
      using rhodamine-123 efflux assays, we observed a significant decrease in P
      glycoprotein activity in caveolin-1 overexpressing cells, similar to that
      observed with 5 microM cyclosporine A or 10 microM verapamil, 2 inhibitors of P
      glycoprotein activity. Using confocal microscopy, subcellular fractionation and
      co-immunoprecipitation assays, a possible physical interaction between caveolin-1
      and P-glycoprotein in the caveolae membrane was observed in Hs578T/Doxo cells
      overexpressing caveolin-1. These results suggest that overexpression of caveolin
      1 changes the state of the cells from drug-resistant to drug-sensitive by
      inhibiting P-glycoprotein transport activity.

PMID- 15239130
TI  - Head and neck tumor sites differ in prevalence and spectrum of p53 alterations
      but these have limited prognostic value.
AB  - The tumor site is a strong clinical factor in head and neck squamous cell
      carcinoma (HNSCC). To clarify the biologic and clinical role of p53 alterations
      in HNSCC, we have examined the prevalence and the nature of p53 alterations in a
      large cohort of tumors from the different sites. For immunohistochemical analysis
      of p53 protein expression, we introduced tyramide signal amplification
      immunohistochemistry (TSA-IHC) on a tissue microarray. This allowed the
      discrimination between normal low-level expression and reduced or lost
      expression. Two hundred fifty-three tumors were subjected to mutational analysis
      by genomic DNA sequencing, employing also the p53 GeneChip from Affymetrix. The
      prevalence of all p53 alterations, i.e., mutations, overexpression and loss of
      expression, was significantly higher in hypopharyngeal tumors than in the other
      sites (p = 0.001). Laryngeal tumors showed the lowest rate of p53 alterations,
      but revealed a distinct mutation spectrum: most mutations affected exon 5 (p =
      0.013) and the S2' domain (p = 0.002), and most hot-spot 248 mutations occurred
      in the larynx (p < 0.001). Sequencing by p53GeneChip technology was shown to be
      only insignificantly more sensitive than dideoxy sequencing. In agreement with
      p53 mutations occurring prior to invasiveness, their prevalence did not increase
      with tumor stage, and all mutation classes lacked prognostic significance. The
      large patient cohort of this study showed that p53 is differentially affected in
      the different tumor sites of the head and neck, but its mode of inactivation does
      not play a major role in tumor progression.

PMID- 15239131
TI  - Expression in bladder transitional cell carcinoma by real-time quantitative
      reverse transcription polymerase chain reaction array of 65 genes at the tumor
      suppressor locus 9q34.1-2: identification of 5 candidates tumor suppressor genes.
AB  - Frequent deletions on 9q34.1-2 were reported in bladder transitional cell
      carcinoma. High deletion mapping studies delimited a critical interval between
      markers D9S61 and D9S66, which is highly susceptible to contain a tumor
      suppressor gene. Expression level of the 65 genes localized in this region was
      analyzed by real-time quantitative RT-PCR, comparing tumor to normal urothelium.
      Five genes exhibited a significantly reduced expression level: C9orf9, KIAA0625,
      ABL1, LAMC3 and KIAA1857-netrin-G2, which exhibited the most significant
      downregulation (p=0.0007). KIAA1857-netrin-G2 belongs to the netrins and might
      then be a tumor suppressor gene in bladder cancer, as netrin1 receptor DCC has
      been implicated in tumorigenesis.

PMID- 15239132
TI  - CHEK2 variant I157T may be associated with increased breast cancer risk.
AB  - Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to
      DNA damage. The CHEK2 1100delC has previously been shown to be a low-penetrance
      breast cancer susceptibility allele. We have evaluated the role of another CHEK2
      variant, I157T in the FHA domain of the gene, for association with breast cancer.
      I157T was found at a significantly higher frequency in the population-based
      series of breast cancer patients (77/1035, 7.4%, odds ratio [OR] = 1.43, 95%
      confidence interval [CI] = 1.06-1.95, p = 0.021) than among population controls
      (100/1885, 5.3%). The frequency in the familial breast cancer patients was not
      elevated (28/507, 5.5%, OR = 1.04, 95% CI = 0.68-1.61). The I157T protein, that
      undermines cellular responses to ionizing radiation and shows deficiency in
      substrate recognition in vivo, was expressed at normal level in tumor tissues as
      well as in cultured cells. The I157T protein was stable and it dimerized with the
      wild-type CHEK2 co-expressed in human cells. These functional properties of the
      I157T protein suggest that this variant may have negative effect on the pool of
      normal CHEK2 protein in heterozygous carrier cells by formation of heterodimers
      with wild-type CHEK2. The I157T variant may be associated with breast cancer
      risk, but the risk is lower than for 1100delC.

PMID- 15239133
TI  - Elevated expression of CCL5/RANTES in adult T-cell leukemia cells: possible
      transactivation of the CCL5 gene by human T-cell leukemia virus type I tax.
AB  - HTLV-I is the etiologic agent of ATL and of tropical spastic paraparesis/HTLV-I
      associated myelopathy. Infiltration of various tissues by circulating leukemic
      cells and HTLV-I-infected T cells is a characteristic of ATL and HTLV-I
      associated inflammatory diseases. Chemokines play important roles in migration
      and tissue localization of various lymphocyte subsets. Here, we report the highly
      frequent expression of CCL5 (RANTES) in ATL and HTLV-I-infected T-cell lines.
      Among various human T-cell lines, those infected with HTLV-I selectively
      expressed the CCL5 gene and secreted CCL5. Furthermore, CCL5 was expressed by
      leukemic cells in peripheral blood and lymph nodes from patients with ATL.
      Inducible expression of HTLV-I transcriptional activator Tax in a human T-cell
      line Jurkat, up-regulated CCL5 mRNA and induced CCL5 secretion. Analysis of the
      CCL5 promoter revealed that this gene is activated by Tax, via the activation of
      NF-kappaB, whose responsive element, R(A/B), is located at positions -71 to -43
      relative to the putative transcription start site. Aberrant expression of CCL5 by
      HTLV-I-infected T cells may impact on the pathophysiology of HTLV-I-associated
      diseases.

PMID- 15239134
TI  - Role of alpha4 integrin and its ligand VCAM-1 in the specific extravasation of a
      tumor-specific TH2 clone into tumor tissue that initiates its rejection.
AB  - The effectiveness of anticancer immunotherapeutic strategies involving the
      transfer of tumor-specific T cells depends on appropriate lymphocyte-endothelial
      cell interactions that facilitate the migration of lymphocytes into tumor. Here,
      we investigated the molecular mechanisms underlying the migration of the antigen
      specific Th2 CD4(+) T-cell clone YS1093 into S1509a tumor tissue. YS1093 is
      specific for the S1509a tumor but does not recognize the S713a tumor. Transfer of
      YS1093 cells into mice bearing both S1509a and S713a tumors caused only the
      S1509a tumor to regress. This regression was markedly inhibited by pretreating
      YS1093 cells with an anti-alpha4 integrin MAb and administering an anti-VCAM-1
      MAb at T-cell transfer. Since vascular endothelial cells in S1509a tumor tissues
      express VCAM-1 and the MHC class II (I-E(k)) molecule restricting YS1093
      activity, labeled YS1093 cells migrated specifically into the S1509a tumor, and
      this migration was also blocked by the anti-TCRbeta F(ab')(2) and anti-I-E(k)
      MAbs. Furthermore, in vitro assays revealed that anti-CD3 MAb-mediated TCR cross
      linkage initiated the binding of alpha4 integrin on YS1093 cells to VCAM-1. This
      adhesive activity was completely blocked by the anti-alpha4 integrin MAb. These
      results strongly suggest that i.v.-transferred YS1093 cells act in tumor
      regression by specifically recognizing their tumor antigen peptide in the context
      of I-E(k) on vascular endothelial cells in the S1509a tumor, which activates the
      binding of alpha4 integrin to VCAM-1 on the endothelial cells, facilitating
      YS1093 extravasation into the tumor. It is likely that this initial migration of
      specific CD4(+) T cells into tumor tissues promotes the subsequent infiltration
      into the tumor of other immunocytes that effect tumor destruction.

PMID- 15239135
TI  - Metalloproteinase inhibition augments antitumor efficacy of the anti-CD30
      immunotoxin Ki-3(scFv)-ETA' against human lymphomas in vivo.
AB  - There is increasing evidence that the shedding of extracellular antigen domains
      impedes selective immunotherapy. One example is CD30, which is overexpressed on
      the surface of malignant lymphoma cells and has been identified as a promising
      target for antibody-based immunotherapy. However, CD30 is cleaved from the
      surface of target cells and the resulting soluble ectodomain (sCD30) is
      protecting the cells from antibody binding. Shedding can be inhibited by
      hydroxamate inhibitors of metalloproteinases such as BB-3644. We thus evaluated
      the influence of BB-3644 on the efficacy of the anti-CD30 single-chain
      immunotoxin Ki-3(scFv)-ETA'. In vitro, the addition of BB-3644 augmented the
      antitumor effect of Ki-3(scFv)-ETA' against Hodgkin-derived L540Cy cells by a
      factor of 2.75. Severe combined immunodeficiency (SCID) mice challenged with CD30
      positive L540Cy cells were treated with the immunotoxin. One single nontoxic dose
      of BB-3644 increased the mean survival time of animals treated concomitantly with
      Ki-3(scFv)-ETA' to 93 days as compared with 35 days in the control (p = 0.0017).
      When BB-3644 was continuously delivered using subcutaneously implanted pumps,
      this effect was even more pronounced with no observed tumor growth in the animals
      within 200 days. Thus, concomitant application of metalloproteinase inhibitors
      might become clinically relevant in antibody-based immunotherapy against targets
      known to be shed from tumor cells.

PMID- 15239136
TI  - Increased expression of inducible HSP70 in apoptotic cells is correlated with
      their efficacy for antitumor vaccine therapy.
AB  - Apoptosis is a physiologic process in normal development, tissue remodeling and
      cell turnover. This cell death is noninflammatory and nonimmunogenic, but when
      associated with a danger signal, it can activate the immune system. However, the
      capacity of apoptotic cells to activate the immune system is not clearly
      established, although dead tumor cells have been largely exploited as a source of
      TAA in cellular therapy against cancer. From these cellular preparations,
      contradictory results have been reported on the effect of apoptotic cells as an
      effective source of TAA and their immunologic properties. These conflicting data
      strongly suggest that the optimal preparation of apoptotic cells derived from
      tumor cells remains to be determined. In this work, we studied and compared the
      efficacy of antitumor immune responses derived from repeated injections using
      different preparations of apoptotic cells. We investigated the importance of
      HSP70 and TGF-beta expression in apoptotic cells used in the treatment of an
      established and nonimmunogenic rat carcinoma. UVB-mediated apoptosis did not
      affect TGF-beta expression in tumor cells, whereas HS treatment sharply
      downregulated it. Thus, downregulation of TGF-beta permits normal DC activation
      and maturation and the induction of tumor immunity. We conclude that HS followed
      by UVB irradiation is a superior source of tumor antigen for the treatment of
      established tumors. Future work will determine whether HS independently
      upregulates HSP70, thereby suppressing expression of active TGF-beta, or whether
      the 2 are linked via a still undefined mechanism.

PMID- 15239137
TI  - Biomarkers of dietary fatty acid intake and the risk of breast cancer: a meta
      analysis.
AB  - The use of the fatty acid composition of adipose tissue, erythrocyte membranes,
      serum and plasma as biological markers of fatty acid intake was recently
      introduced in epidemiological studies. The biomarkers of fatty acid intake have
      the advantage of providing quantitative measurement independent of energy intake
      and of the subject's memory. We performed a meta-analysis of published results of
      epidemiological studies of the composition of fatty acids in biological samples
      and breast cancer risk. The analysis was based on 3 cohort and 7 case-control
      studies including 2,031 cases and 2,334 controls. The summary statistic used was
      the average of the relative risk estimated for each level of the fatty acid on
      study, weighted by the inverse of its variance. Random effect models were assumed
      when the test for heterogeneity was significant. Overall relative risks were
      estimated for studies including pre- and post-menopausal breast cancer and
      separately for post-menopausal women. In cohort studies, a significant protective
      effect was found for total n-3 polyunsaturated fatty acids, while total
      monounsaturated fatty acids, oleic acid (C18:1 n-9c) and palmitic acid (C16:0)
      were significantly associated with an increase of breast cancer risk. Total
      saturated fatty acids were significantly associated with breast cancer risk in
      cohort studies only in postmenopausal women. For case-control studies, the only
      finding was for alpha linolenic acid (C18:3, n-3), which showed an inverse
      association bordering on statistical significance. The findings of cohort studies
      fit well with hypotheses derived from experimental animal studies. More
      epidemiological cohort studies that integrate biological markers of dietary fatty
      acid intake are needed in order to determine the contribution of different types
      of fatty acids in the etiology of breast cancer.

PMID- 15239138
TI  - CNTO 328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in
      nude mice.
AB  - IL-6 is a multifunctional cytokine implicated in several cancers. IL-6 is a
      growth factor for certain tumors and contributes to drug resistance, cachexia and
      bone resorption. Cachexia is characterized by progressive weight loss and
      depletion of host reserves of adipose tissue and skeletal muscle. We have
      developed CNTO 328 (cCLB8), a human-mouse chimeric MAb to IL-6 (K(d) approx. 10(
      12) M) that inhibits IL-6 function. A phase I study with CNTO 328 in multiple
      myeloma patients demonstrated that the antibody was safe and had a circulating
      half-life of approximately 17 days. Since IL-6 is implicated in cachexia, we
      hypothesized that CNTO 328 could inhibit tumor-induced cachexia. We used 2 human
      tumor-induced cachexia models in nude mice. In the first model, human melanoma
      cells were inoculated in female nude mice. Control treated animals lost 19% (+/
      7.7%) body weight from day 0 to day 31, whereas CNTO 328 (10 mg/kg)-treated
      animals lost only 1.5% (+/-1.3%) body weight from day 0 to day 31 (p = 0.023). In
      the second cachexia model, human prostate tumor cells were injected into male
      nude mice. By day 29, control treated animals lost 6% (+/-3.5%) body weight,
      whereas CNTO 328 (10 mg/kg)-treated animals gained 7% (+/-4%) body weight (p =
      0.01). Since CNTO 328 blocks human IL-6 but not mouse IL-6, the data indicate
      that tumor cell-secreted IL-6 directly contributes to body weight loss,
      highlighting the potential role for CNTO 328 as an anticachectic agent.

PMID- 15239139
TI  - Antimetastatic activity of the photodynamic agent hypericin in the dark.
AB  - A unique property of the photodynamic signal transduction inhibitor hypericin
      (HY) is high functionality in the dark, which has been shown to result in
      portfolio of anticancer activities both in vitro and in vivo. Here we show that
      treatment with HY significantly reduces growth rate of metastases in 2 murine
      models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2). Focus on
      metastases was achieved by resection of primary tumors at stages in which
      micrometastases exist in lungs. Long-term animal survival in DA3 tumor-excised
      groups increased from 15.6% in controls to 34.5% following supplementary
      treatment with HY. In mice bearing SQ2 tumor metastases, therapy with HY
      increased animal survival from 17.7% in controls to 46.1%. Using Laser-induced
      fluorescence and multipixel spectral image analyses, we demonstrate that HY has a
      high tendency to accumulate in primary and metastatic tumors; HY content in lungs
      bearing metastases was approximately 2-fold higher than in the lungs of healthy
      animals. The tendency of HY to preferentially concentrate in lung metastases,
      combined with its potent antiproliferative activities, may render HY as a useful
      supplementary modality in the treatment of metastatic cancer irrespective of
      photoactivation.

PMID- 15239140
TI  - Combretastatin family member OXI4503 induces tumor vascular collapse through the
      induction of endothelial apoptosis.
AB  - The mechanism of tumor cell killing by OXI4503 was investigated by studying
      vascular functional and morphological changes post drug administration. SCID mice
      bearing MHEC5-T hemangioendothelioma were given a single dose of OXI4503 at 100
      mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50%
      at 1 hr, and reached a maximum level 6-24 hr post drug treatment. Tumor vascular
      permeability, measured by Evan's blue and hemoglobin, increased significantly
      from 3 hr and peaked at 18 hr. The elevated tumor vessel permeability was
      accompanied by an increase in vascular endothelial growth factor (VEGF) from 1 hr
      post drug treatment. Immunohistochemical staining for CD31 and laminin showed
      that tumor blood vessels were affected as early as 3 hr but more prominent from 6
      hr. From 12 hr, the vessel structure was completely destroyed. Histopathological
      and double immunohistochemical staining showed morphological change and induction
      of apoptosis in endothelial cells at 1-3 hr, followed by tumor cell necrosis from
      6-72 hr. There were no statistically significant changes of Evan's blue and
      hemoglobin contents in liver tissue over the time course. These results suggest
      that OXI4503 selectively targets tumor blood vessels, and induces blood flow
      shutdown while it enhances tumor blood vessel permeability. The early induction
      of endothelial cell apoptosis leads to functional changes of tumor blood vessels
      and finally to the collapse of tumor vasculature, resulting in massive tumor cell
      necrosis. The time course of the tumor vascular response observed with OXI4503
      treatment supports this drug for development as a stand alone therapy, and also
      lends support for the use of the drug in combination with other cancer therapies.

PMID- 15239141
TI  - Omega-3 fatty acids improve liver and pancreas function in postoperative cancer
      patients.
AB  - Epidemiologic studies have indicated that high intake of saturated fat and/or
      animal fat increases the risk of colon and breast cancer. Omega-3 PUFAs in fish
      oil (FO) can inhibit the growth of human cancer cells in vitro and in vivo. These
      effects are related to the uptake of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) into the cellular substrate pool and their competitive
      metabolism with arachidonic acid (AA) at the cyclooxygenase and 5-lipoxygenase
      levels. The metabolites of EPA and DHA have less inflammatory and
      immunosuppressant potency than the substances derived from AA. Based on previous
      experimental data, we hypothesized that FO supplementation after major abdominal
      cancer surgery would improve hepatic and pancreatic function. Ours was a
      prospective, randomized, double-blinded clinical trial on 44 patients undergoing
      elective major abdominal surgery, randomly assigned to receive total parenteral
      nutrition (TPN) supplemented with either soybean oil (SO 1.0 g/kg body weight
      daily, n = 20) for 5 days or a combination of FO and SO (FO 0.2 + SO 0.8 g/kg
      body weight daily, n = 24). Compared to pure SO supplementation in the
      postoperative period, FO significantly reduced ASAT [0.8 +/- 0.1 vs. 0.5 +/- 0.1
      mmol/(l. sec)], ALAT [0.9 +/- 0.1 vs. 0.6 +/- 0.1 mmol/(l. sec)], bilirubin (16.1
      +/- 5.3 vs. 6.9 +/- 0.6 mmol/l), LDH (7.7 +/- 0.4 vs. 6.7 +/- 0.4 mmol/(l. sec)
      and lipase (0.6 +/- 0.1 vs. 0.4 +/- 0.1 micromol/(l. sec) in the postoperative
      course. Moreover, patients with increased risk of sepsis (IL-6/IL-10 ratio >8)
      showed a tendency to shorter ICU stay (18 hr) under omega-3 PUFA treatment.
      Weight loss as encountered after the SO emulsion of 1.1 +/- 2.2 kg was absent in
      the FO group. After major abdominal tumor surgery, FO supplementation improved
      liver and pancreas function, which might have contributed to the faster recovery
      of patients.

PMID- 15239142
TI  - Concise prediction models of anticancer efficacy of 8 drugs using expression data
      from 12 selected genes.
AB  - We developed concise, accurate prediction models of the in vitro activity for 8
      anticancer drugs (5-FU, CDDP, MMC, DOX, CPT-11, SN-38, TXL and TXT), along with
      individual clinical responses to 5-FU using expression data of 12 genes. We first
      performed cDNA microarray analysis and MTT assay of 19 human cancer cell lines to
      sort out genes which were correlative in expression levels with cytotoxicities of
      the 8 drugs; we selected 13 genes with proven functional significance to drug
      sensitivity from a huge number of potent prediction marker genes. The correlation
      significance of each was confirmed using expression data quantified by real-time
      RT-PCR, and finally 12 genes (ABCB1, ABCG2, CYP2C8, CYP3A4, DPYD, GSTP1, MGMT,
      NQO1, POR, TOP2A, TUBB and TYMS) were selected as more reliable predictors of
      drug response. Using multiple regression analysis, we fixed 8 prediction formulae
      which embraced the variable expressions of the 12 genes and arranged them in
      order, to predict the efficacy of the drugs by referring to the value of Akaike's
      information criterion for each sample. These formulae appeared to accurately
      predict the in vitro efficacy of the drugs. For the first clinical application
      model, we fixed prediction formulae for individual clinical response to 5-FU in
      the same way using 41 clinical samples obtained from 30 gastric cancer patients
      and found to be of predictive value in terms of survival, time to treatment
      failure and tumor growth. None of the 12 selected genes alone could predict such
      clinical responses.

PMID- 15239143
TI  - Allelic loss but absence of mutations in the polyspecific transporter gene BWR1A
      on 11p15.5 in hepatoblastoma.
AB  - Chromosomal region 11p15.5 shows frequent maternal allelic loss in embryonal
      tumors, including rhabdomyosarcoma (RMS), Wilms' tumor (WT) and hepatoblastoma
      (HB), consistent with the presence of at least one tumor suppressor gene in this
      region, which should be paternally imprinted, i.e., expressed from the maternal
      allele only. The BWR1A gene encodes a polyspecific transmembrane transporter and
      is located on 11p15.5. It is highly expressed in liver, paternally imprinted and
      was found to be mutated in an RMS cell line, making it a plausible tumor
      suppressor gene for HB. We therefore screened 62 HBs, 3 HB cell lines and 1
      pediatric hepatocellular carcinoma for BWR1A mutations using single-strand
      conformation polymorphism analysis. Allelic loss on 11p15.5 was assessed by PCR
      based microsatellite analysis in 56 of the cases for which constitutional DNA was
      available. BWR1A mRNA expression was determined in 14 HBs by differential RT-PCR
      of matched cDNA samples from tumor and normal liver. Western blot analysis was
      performed on 4 tumors and matching normal liver tissue. Except for sequence
      polymorphisms (in exons 2, 3 and 10 as well as in introns 6 and 7), no mutations
      were found. Thirteen HBs (23%) had allelic loss on 11p15.5; this included BWR1A
      in 12 but it was telomeric to BWR1A in 1. Expression of BWR1A mRNA was reduced in
      11 out of 14 cases by 19-92%, independent from allelic loss of 11p15.5. By
      Western blot analysis, all 4 tumors and matching liver samples displayed a 48-51
      kd band corresponding to BWR1A. These results make it unlikely that BWR1A is the
      target of the allelic deletions in HB. However, similar to the putative 11p15.5
      tumor suppressor H19, BWR1A appears to be reduced in expression. Reduced
      expression in the absence of mutations may contribute to HB development; however,
      to understand the significance of this finding will require further studies on
      the function of BWR1A, specifically its role in liver development.

PMID- 15239144
TI  - National Polyp Study data: evidence for regression of adenomas.
AB  - The data of the National Polyp Study, a large longitudinal study on surveillance
      of adenoma patients, is used for testing assumptions on the adenoma-carcinoma
      sequence. The observed adenoma and colorectal cancer incidence in the National
      Polyp Study were compared with the simulated outcomes of the MISCAN-COLON model
      of epidemiology and control of colorectal cancer for the U.S. population based on
      expert opinion. Variants of this model were explored in order to identify
      assumptions on the adenoma-carcinoma sequence that are consistent with the study
      observations. The high observed adenoma detection rates at surveillance and low
      observed colorectal cancer incidence in the National Polyp Study could only be
      explained by assuming a high incidence rate of adenomas accompanied by regression
      of adenomas. The National Polyp Study data suggest that adenoma prevalence
      results from a dynamic process of both formation as well as regression of
      adenomas. This lowers the expectations for the effects of colorectal cancer
      screening strategies that focus on adenoma detection.

PMID- 15239145
TI  - KLF6 is not the major target of chromosome 10p losses in glioblastomas.

PMID- 15239146
TI  - Absence of KLF6 gene mutations in human astrocytic tumors and cell lines.

PMID- 15239149
TI  - Golf and back pain relief.

PMID- 15239147
TI  - Absence of mutations in the putative tumor suppressor gene KLF6 in glioblastomas
      and meningiomas.

PMID- 15239150
TI  - New drug helps Parkinson's "off" periods.

PMID- 15239151
TI  - Statins may slow MS progression.

PMID- 15239152
TI  - Colon cancer surgeries compared. In patients with certain characteristics,
      laparoscopically assisted colectomy works well.

PMID- 15239153
TI  - Biopsies for "normal" PSA? Certain relatively young, healthy men with PSA levels
      below 4 should consider having a biopsy.

PMID- 15239154
TI  - Guidelines for new epilepsy drugs. New epilepsy drugs are safer and cause fewer
      adverse effects than their predecessors. But they're not more effective.

PMID- 15239155
TI  - Exercise advice for stroke survivors.

PMID- 15239156
TI  - Clogged neck arteries, no symptoms--should you have surgery?

PMID- 15239157
TI  - Painkillers can trigger chronic headaches.

PMID- 15239158
TI  - Older women face higher risk of post-shingles pain.

PMID- 15239159
TI  - Modified therapy for heart failure extends life. For some people with heart
      failure, a combination of two existing treatments lessens symptoms and delays
      death.

PMID- 15239160
TI  - An "ACE" in the hole for fixing atrial fibrillation?

PMID- 15239161
TI  - Statins may fight heart failure.

PMID- 15239162
TI  - New treatment for fecal incontinence.

PMID- 15239164
TI  - More on low-carb diets.

PMID- 15239163
TI  - A new risk factor for fractures? Diets low in B vitamins may leave people more
      prone to broken bones.

PMID- 15239165
TI  - Diabetes linked to higher risk of Alzheimer's disease.

PMID- 15239166
TI  - For elderly, who decides who can stay home alone? Judges--not doctors--have the
      final say.

PMID- 15239167
TI  - Lyme disease on the rise.

PMID- 15239168
TI  - Here's the rub on painkilling creams.

PMID- 15239169
TI  - Mammograms more often misread in obese women.

PMID- 15239170
TI  - Questions & answers. I'm confused about the new carbohydrate claims on foods.
      What does "low carb" really mean, and what is a net carb?

PMID- 15239171
TI  - Questions & answers. Of all the treatments that promise to improve the appearance
      of aging skin, which ones have been medically proven to actually work?

PMID- 15239172
TI  - Evaluation of the prevalence of antiwheat-, anti-flour dust, and anti-alpha
      amylase specific IgE antibodies in US blood donors.
AB  - BACKGROUND: Asthma in bakery workers is one of the most frequently occurring
      forms of occupational asthma in the world. Experience from other countries has
      shown the prevalence of sensitization (IgE) to bakery-associated allergens (BAAs)
      (wheat [W], flour dust [FD], alpha-amylase [AA]) in bakery workers to be 5% to
      53%, whereas the prevalence in nonoccupationally exposed individuals was
      estimated to be 1.2% to 6.4%. OBJECTIVE: To estimate the prevalence of BAA
      sensitization by measuring BAA specific IgE in the residual serum tubes of
      volunteer blood donors. METHODS: Serum samples from 534 volunteer blood donors
      were measured for anti-W, anti-FD, and anti-AA specific IgE antibodies (in
      duplicate) using the AlaSTAT microplate assay. Samples with BAA IgE
      concentrations of 0.35 kU/L or greater were considered positive. RESULTS:
      Nineteen of 530 serum samples (3.6%; 95% confidence interval [CI], 3.3%-3.9%)
      were positive for W (range, 0.38-3.61 kU/L), whereas 31 of 534 (5.8%; 95% CI,
      5.3%-6.3%) were positive for FD (range, 0.35-2.34 kU/L) and 5 of 529 (1.0%; 95%
      CI, 0.9%-1.1%) were positive for AA (range, 0.38-1.59 kU/L). Thirteen serum
      samples were positive for both W and FD; 1 sample each was positive for W and AA
      and FD and AA. CONCLUSIONS: The prevalence of IgE sensitization in serum samples
      from a relatively large unselected population of volunteer blood donors is 1.0%
      for AA, 3.6% for W, and 5.8% for FD, which agrees well with data from other
      countries for sensitization prevalence rates for nonoccupationally exposed
      individuals.

PMID- 15239173
TI  - HIV and sexual health in the UK: politics and public health.

PMID- 15239174
TI  - No "access for all" to US Government HIV/AIDS research.

PMID- 15239175
TI  - Who receives inpatient charity care in California?

PMID- 15239176
TI  - [Pharmaceutical promotion, major role in new prescriptions].

PMID- 15239177
TI  - [The fight against obesity passed by prevention].

PMID- 15239178
TI  - The implementation of Medicare's outpatient prospective payment system and
      specific concerns for rural hospitals.
AB  - The transition to Medicare's new prospective payment system for hospital
      outpatient services has arguable been the most complex and difficult programmatic
      change in the history of Medicare (Federal Register, 2002). Concern about its
      adverse effects led to holding rural hospitals with 100 beds or fewer harmless
      from the financial consequences of the new payment system for the first three
      years. However, small rural hospitals were not held harmless from implementing
      the outpatient prospective payment system (OPPS). Many outside observers felt
      that small rural hospitals would be ill-equipped to handle the immensity of
      change required, and that claim denials or delays caused by inaccurate claims
      submissions might have a disproportionate effect on smaller hospitals. There were
      also reports about difficulties with the interim payment system that had been
      designed to ensure small hospitals did not lose money during the first three
      years. This policy brief describes issues that arose in implementing OPPS during
      the first years of the program, identifies specific implementation concerns for
      small rural hospitals, and raises issues that may warrant further research or
      policy action.

PMID- 15239179
TI  - [Puncture of the common iliac vein during cystostomy].

PMID- 15239180
TI  - A physician's duty to warn family members of genetic risks: limiting the
      importance of Tarasoff.
AB  - This paper addresses whether a physician should be held liable for failing to
      warn family members of potential risks of genetic disease. Resolution of this
      complex issue requires consideration of physician-patient responsibility, the
      psychological impact of the warning, the efficacy of genetic testing, and the
      need to protect the physical well being of family members. The paper concludes
      that application of the Tarasoff factors, which focus primarily on the
      foreseeable aspect of the threat and the identifiable nature of the third
      parties, is an insufficient means for determining whether this duty to disclose
      exists. Instead, in addition to the Tarasoff factors, a physician must consider a
      number of case-specific factors in deciding whether the benefits of disclosure
      outweigh the psychological effects of knowing of the disease and the public
      policy reasons behind physician-patient confidentiality. Likewise, a court should
      consider these same factors as applied to a hypothetical "reasonable physician"
      before concluding that a specific physician has a duty to warn family members
      potential of genetic threats.

PMID- 15239182
TI  - The secret to superior leadership.

PMID- 15239181
TI  - Informed consent in clinical research: policies and practices in Singapore.
AB  - The policies and practices for obtaining informed consent from research subjects
      in clinical research play a vital role in determining a nation's success as a
      center for clinical research. The difficulty lies in the fact that while on the
      one hand, informed consent is a necessary pre-condition for ethical clinical
      research, a scrupulous observance of the guidelines for informed consent could,
      on the other hand, cripple medical research. Crippling of ethical medical
      research can be adverse to public interest, and consequently, unethical. Hence, a
      fine balance must be struck in the application of the guidelines for obtaining
      informed consent. This, in turn, would depend on the constitution and skill of
      research ethics committees who are appointed to consider and approve clinical
      research proposals. The discussion below addresses the above difficulty with
      recommendations that could further enhance Singapore's image as a regional
      clinical trial hub.

PMID- 15239183
TI  - When employees become ambassadors.

PMID- 15239184
TI  - Common customer service mistakes and how to avoid them.

PMID- 15239185
TI  - Stem cell research.

PMID- 15239186
TI  - Cloning's slippery slope: how embryonic cloning leads to human cloning.

PMID- 15239187
TI  - Feedstock supply, logistics, processing, and composition.

PMID- 15239188
TI  - 'War surgery at sea': maritime trauma experience in the Gulf War 2003.
AB  - During the second Gulf War in 2003, the Primary Casualty Receiving facility
      onboard R.F.A. Argus treated thirty six patients with injuries sustained in the
      conflict, including thirty Iraqi enemy prisoners of war and displaced persons.
      Their injuries and operative management are reported. Eighteen casualties
      sustained fragmentation injuries, six casualties sustained gunshot wounds and
      seven casualties suffered a combination of both. In addition to penetrating
      missile injuries five casualties from road traffic accidents were treated. All
      wounds were managed following the established principles of war surgery. The
      extremities were involved in twenty eight patients (78%) including nine open,
      multifragmented long bone fractures which were managed with external skeletal
      fixators. Two laparotomies and one thoracotomy were performed. The average
      duration of surgery was one hundred and thirty two minutes with the longest
      procedure lasting for six hours and ten minutes. This was the first time that the
      Primary Casualty Receiving Facility had been used to surgically manage war
      casualties and it fulfilled this role to good effect.

PMID- 15239189
TI  - Immediate life support training in an operational environment.
AB  - The Immediate Life Support (ILS) course is a 1 day programme designed by the
      Resuscitation Council (UK) to bridge the gap between Basic Life Support (BLS) and
      Advanced Life Support (ALS). During the build up to Operation TELIC, the aim was
      to provide ILS training to all staff who may be involved in the acute care of
      patients within PCRF ARGUS, and also to members of staff from other units who may
      be involved in similar situations. In total, 101 staff received ILS training
      during Op TELIC, all of whom were successful in completing the course.

PMID- 15239190
TI  - Operative shortening of the elongated defunctioned tendoachillies following
      previous rupture.
AB  - Healing of the tendoachilles (TA) following rupture may result in lengthening
      over a long segment rather than discrete scar interposition. We describe our
      experience and results of a direct TA shortening technique of dysfunctionally
      long TAs. Five patients presented with impairment of their sporting level. Four
      patients had TA injuries that were managed by physiotherapy alone and 1 had been
      cast immobilised for 6 weeks. At open operation the TAs were found to be
      confluent but with evidence of scarring over a long segment. A 'Z' shortening was
      performed. The patients were reviewed up to a mean of 30 months post op. The
      overall scores were excellent in 1, good in 3 and fair in 1. All returned to
      their chosen level of sporting activity. The technique described is relatively
      straightforward and gives predictable improvement in function. It is therefore a
      useful technique in this often-unrecognised condition

PMID- 15239191
TI  - Establishment of cDNA microarray analysis at the Genomic Medicine Research Core
      Laboratory (GMRCL) of Chang Gung Memorial Hospital.
AB  - BACKGROUND: Advances in molecular and computational biology have led to the
      development of powerful, high-throughput methods for analysis of differential
      gene expression, which are opening up new opportunities in genomic medicine. DNA
      microarray technology has been enthusiastically integrated into basic biomedical
      research and will eventually become a molecular monitoring tool for various
      clinical courses. METHODS: As a core research facility of Chang Gung University
      (CGU) and Chang Gung Memorial Hospital (CGMH), the Genomic Medicine Research Core
      Laboratory (GMRCL) welcomes investigators from every discipline to employ DNA
      microarray technology in the quest for knowledge of genomic medicine. The first
      tasks for GMRCL are to optimize the standard operating procedures (SOP) for each
      instrument and to assure the quality of every procedure. RESULTS: During the
      first year after the establishment of the GMRCL at the CGMH, we tested and
      adopted procedures that were satisfactory for our purposes. These procedures
      included: replication of bacterial stocks, amplification of human DNA clones,
      annotation of each DNA clone, production of cDNA microarrays, validation of RNA
      quality and quantity, labeling of target specimens, competitive hybridization,
      scanning of slides, data analysis, and post-microarray validation of results. We
      present a summarization of the materials and procedures used at the GMRCL and
      discuss the reasons for using them. CONCLUSIONS: The information about the cDNA
      microarray analysis system at the GMRCL is compliant with the minimal information
      about a microarray experiment (MIAME) format. The information may be useful to
      both the investigators who are using this core facility and researchers at other
      institutes, who will establish their own in-house cDNA microarray systems.

PMID- 15239193
TI  - Nonunion of the femur treated with conventional osteosynthesis combined with
      autogenous and strut allogeneic bone grafts.
AB  - BACKGROUND: In this study, we reviewed the results of conventional osteosynthesis
      combined with strut onlay allografts and autogenous bone grafts as the treatment
      for nonunion of the femur. METHODS: We conducted a retrospective study of 18
      patients with nonunion of the femur treated with internal fixation (eight 95
      degree fixed-angled blade plates, 7 intramedullary nails, 2 dynamic hip
      compression plates and screws, and 1 condylar buttress plate) and autogenous bone
      grafts and cortical strut allografts. There were 1.8 operations on average before
      surgery. The average time from the initial treatment of the fracture or osteotomy
      to surgery was 32.5 months. The average follow-up was 32.2 months. RESULTS: All
      18 nonunions had healed by the time of follow-up. Positive intraoperative
      cultures (Staphylococcus epidermidis) in 2 patients were resolved by parenteral
      antibiotics with no additional treatment. Removal of implants was required in 5
      patients because of screw irritation or bony union. One concomitant
      quadricepsplasty as well as 2 excisions of a protruding graft were required
      because of restricted knee motion or impingement. CONCLUSIONS: For difficult
      nonunions of the femur in the current study, strict adherence to the principles
      of the treatment of nonunion and the addition of strut allografts to enhance
      stability and repair potential proved to be a good alternative.

PMID- 15239192
TI  - Minimally invasive treatment of osteoporotic vertebral compression fracture.
AB  - BACKGROUND: The use of percutaneous vertebroplasty (PV) to treat osteoporotic
      vertebral fractures is increasing. This investigation assesses the efficacy and
      safety of PV for refractory pain owing to osteoporotic vertebral compression
      fractures. METHODS: A retrospective investigation of PV was conducted with a
      minimal of 1 year follow up. PV with polymethylmethacrylate (PMMA) was performed
      on 75 patients with osteoporotic vertebral compression fractures that responded
      poorly to the conservative therapy. Patients were asked to quantify their degree
      of pain using Huskisson's visual analogue scale to assess the clinical results.
      RESULTS: Eighty-seven vertebrae treated using PV in 70 patients were evaluated
      with a minimal of 1 year follow up. Pain, as assessed on the VAS, decreased from
      80+/-16 mm before PV to 36+/-28 mm at 1 month after PV and 30+/-19 mm at the most
      recent follow up. The reduction in pain from the baseline to 1 month (p=0.031)
      and to final follow up (p=0.023) were both statistically significant. Sixty-two
      patients (85.5%) quickly returned to their pre-injury activity level and achieved
      better quality of life. CONCLUSIONS: PV is effective in pain reduction for
      painful vertebral compression fractures. It provided significant pain relief.
      Skillful techniques and careful safeguards can minimize the risks of PMMA
      migration.

PMID- 15239194
TI  - Breast reconstruction with a muscle-sparing free transverse rectus abdominis
      myocutaneous flap: comparison between immediate and delayed groups.
AB  - BACKGROUND: Breast reconstruction offers not only physical but also psychological
      rehabilitation. Autologous tissue transfer is a good option for breast
      reconstruction. The purpose of this study was to investigate the success rate,
      complications, and cosmetic outcomes following use of a muscle-sparing free
      transverse rectus abdominis myocutaneous (TRAM) flap for breast reconstruction.
      METHODS: Between August 1999 and February 2001, 15 consecutive patients underwent
      breast reconstruction using a muscle-sparing free TRAM flap after a mastectomy.
      Ten patients received mastectomies and immediately underwent breast
      reconstruction using muscle-sparing free TRAM flaps at Chang Gung Memorial
      Hospital. The remaining 5 patients first received a modified radical mastectomy
      and then underwent breast reconstruction. RESULTS: The mean age of patients was
      43.9 (range, 32 to 50) years. Ten patients (67%) underwent immediate
      reconstructions, and 5 (23%) underwent delayed reconstructions. The overall
      success rate was 93.3%. Postoperative complications included 1 abdominal seroma
      and 1 small area of breast fat necrosis. Six of 10 patients with immediate
      reconstruction underwent both adjuvant chemotherapy and hormone therapy, while 3
      patients received only chemotherapy. None of these adjuvant therapies were
      delayed by the reconstructive surgery. At a mean follow-up of 26.7 months, no
      local recurrence had been found, and 93% of patients were satisfied with the
      esthetic results. CONCLUSIONS: A muscle-sparing free TRAM flap is a good option
      for breast reconstruction. Both the success rate and patient satisfaction are
      high. The subsequent adjuvant therapy need not be delayed following immediate
      reconstruction.

PMID- 15239195
TI  - Computer-aided reconstruction of traumatic fronto-orbital osseous defects:
      aesthetic considerations.
AB  - BACKGROUND: In addition to functional goals, a satisfactory aesthetic outcome is
      important for reconstruction of fronto-orbital osseous defects. The purpose of
      this study is to report on a method for presurgical fabrication of custom
      implants using 3-dimensional (3-D) imaging data and computer-assisted
      manufacturing techniques. METHODS: Preoperative 3-D computed tomography data were
      processed and displayed for evaluation of defects. Implants were created by a
      computer-aided design/computer-aided manufacturing (CAD/CAM) program. A rapid
      prototyping system was applied for production of the physical models. Rehearsal
      of surgery was performed using the implants and skull models. Negative castings
      were created and were used during the operations to prepare the surgical implant
      utilizing methyl methacrylate. Traumatic fronto-orbital defects in 4 patients
      were reconstructed using this method. The follow-up period ranged from 29 to 55
      months. RESULTS: Results showed that the custom implants perfectly fit the
      defects during the operation. Symmetry and normal fronto-orbital contours were
      achieved. There were no peri- or postoperative complications. All patients were
      satisfied with the results. CONCLUSIONS: Computer-aided presurgical simulation
      and fabrication of implants is a reliable and effective method for the
      reconstruction of traumatic fronto-orbital defects, with reduced anesthesia time
      and improved aesthetic outcomes.

PMID- 15239196
TI  - The effects of ciprofloxacin on chest radiographic regression in patients with
      drug intolerance or resistant tuberculosis.
AB  - BACKGROUND: The aim of this study was to identify the clinical efficacy of
      ciprofloxacin as a second-line anti-tuberculosis agent in pulmonary tuberculosis
      patients with drug intolerance or resistance. METHODS: There were 20 patients
      with drug related adverse effects or drug resistance enrolled in the
      ciprofloxacin treatment group (CG). There were also 32 patients enrolled in the
      non-ciprofloxacin treatment group (NCG) that maintained conventional drug
      regimens or the addition of other drugs like streptomycin. The radiographic
      presentation was evaluated using score grading. The speed and outcome of
      regression in the chest radiographic presentations were also evaluated. RESULTS:
      Data showed the CG had significantly more rapid regression than the NCG in drug
      resistant patients (p < 0.01). For the adversely effected patients in the CG, the
      mean scores of pre- and post-treatment were 3.1+/-0.2 and 2.2+/-0.3 (p < 0.001),
      respectively. For the adversely effected patients in the NCG, the mean score of
      pre-treatment was 3.7+/-0.4 and post-treatment mean score was 3.0+/-0.4 (p <
      0.05). For the drug-resistant patients in the CG, the mean scores of pre- and
      post-treatment were 4.3+/-0.4 and 3.4+/-0.5 (p < 0.05), respectively. For the
      drug-resistant patients in the NCG, the mean score of pre-treatment was 3.7+/-0.3
      and post-treatment mean score was 3.2+/-0.3 (no significant difference).
      Obviously, the CG had the same effects compared with the NCG in adverse-effect
      group. On the other hand, the CG had the tendency of more rapid radiographic
      regression and better radiographic outcomes than the NCG in drug-resistant
      patients. CONCLUSIONS: Ciprofloxacin provides a better option for second-line
      drug treatment for pulmonary tuberculosis when patients cannot use conventional
      anti-tuberculosis agents.

PMID- 15239197
TI  - Charcot-Marie-Tooth disease type 1A: a clinical, electrophysiological,
      pathological, and genetic study.
AB  - Various clinical manifestations, electrophysiological findings, and sural nerve
      biopsies are reported in a Taiwanese family with type 1A Charcot-Marie-Tooth
      disease (CMT-1A). In addition, molecular genetic studies for duplication of the
      peripheral myelin protein 22 (PMP22) gene were also performed. There were 3
      patients (2 men and 1 woman) with ages at onset ranging from 37 to 44 years. The
      onset of symptoms was insidious, and the neurological manifestations included
      distal muscle weakness and wasting, mild sensory loss, and hyporeflexia or
      areflexia. The severity of clinical manifestations varied from mild to severe,
      although with very prominent demyelinating polyneuropathy in electrophysiological
      studies. The sural nerve biopsy study revealed demyelination and an onion-bulb
      appearance. The molecular genetic studies confirmed duplication of the PMP22 gene
      in chromosome 17p11.2-12. We conclude that the clinical presentations,
      electrophysiological studies, and pathological studies as well as the molecular
      genetic analysis remain important in the clinical diagnosis of CMT-1A.

PMID- 15239198
TI  - Variable expressivity in a family with Kabuki make-up (Niikawa-Kuroki) syndrome.
AB  - Kabuki make-up syndrome (KS), also called Niikawa-Kuroki syndrome, is a rare
      congenital disorder of unknown etiology. Most KS cases occur sporadically and
      familial KS had never been reported in Taiwan. I describe four individuals in one
      family with KS. Significant intrafamilial variability in the clinical expression
      of this syndrome is evident. In addition to the typical craniofacial dysmorphism
      and cleft palate and/or cleft lip that the three children inherited from their
      father, rare anomalies such as lower lip pits and growth hormone deficiency in
      one girl and right-sided acrotia in one boy were noted. High-resolution banding
      did not detect any chromosomal structural anomalies. These findings further
      suggested the autosomal inheritance (from the father to two sons and one
      daughter) in KS and highlighted the overlapping phenotype with van der Woude
      syndrome.

PMID- 15239199
TI  - Immediate toe transfer following index finger amputation for extensive giant cell
      tumor of the tendon sheath with intraosseous invasion.
AB  - Giant cell tumor of the tendon sheath (GCTTS) is the second most common benign
      tumor of the hand. Although bony indentation from external compression by the
      GCTTS is frequently seen on x-ray film, the intraosseous invasion is relatively
      rare and is a sign for high recurrence. We present a woman with extensive GCTTS
      located in the left index finger at the level of distal interphalangeal joint. X
      ray films revealed multiple osteolytic cystic cavities in the shaft of the middle
      phalanx. Amputation of the index finger at the base of the middle phalanx was
      performed because of extensive bony involvement and concern about possible
      recurrence from inadequate excision. Her left second toe was transferred to
      replace the amputated index finger in the same session. Follow-up examination at
      15 months postoperative revealed good function and appearance of the
      reconstructed index.

PMID- 15239200
TI  - Pessimistic mood in decompensated narcissistic patient.
AB  - We report the negative emotional state as pessimistic mood of a case with
      narcissistic personality disorder during the period of narcissistic
      decompensation. In addition, we identified the clinical differences between
      pessimistic mood and depressive disorder. An 28-year-old unmarried woman
      experienced herself, her life and the external object as futile and disappointing
      after repeated failure to satisfy her grandiose fantasies about the search for
      ideal love. The patient then gave up her formerly gratifying activities, and fell
      into a prolonged state of negative emotions and passivity dominated by
      pessimistic mood characterized by an overwhelming sense of futility. The patient
      did not respond to medical treatment with antidepressants firstly. However after
      a 2-year course of intensive psychotherapy, the patient was able to restore her
      zest to find a new boyfriend with a more rational and realistic attitude.
      Clinically, decompensated narcissistic patients do not exhibit the typical
      attitude of worthlessness or guilty feelings, and are devoid of certain specific
      depressive emotions (e.g., sadness, sorrow, etc.). In contrast, decompensated
      narcissistic patients with pessimistic mood exhibit a dominant sense of futility
      and other negative emotions presented as outrage and disappointment. The purpose
      of this case report was to emphasize the importance to recognize clinical
      features of pessimistic mood for the differential diagnosis and management of the
      decompensated narcissistic patient.

PMID- 15239201
TI  - Factors predicting severity of tinnitus: a population-based assessment.
AB  - The Blue Mountains Hearing Study (BMHS) has shown that tinnitus affects one in
      three older Australians with 16% of cases describing severe annoyance. Among
      persons describing severe symptoms, 52% have sought professional help. We aim to
      identify factors associated with the severity of tinnitus in 2,015 persons aged
      over 54 years. Comprehensive questionnaires about hearing were administered. Air-
      (250-8000 Hz) and bone-conduction (500-4000 Hz) audiometric thresholds of both
      ears, together with transient evoked and spontaneous otoacoustic emissions, were
      measured. Factors predicting severity of tinnitus were assessed in Cox
      proportional hazard models. After multivariate adjustment, factors significantly
      associated with severe tinnitus were hearing loss (relative risk [RR] 2.9),
      dizziness (RR 2.0), head injury (RR 2.0), sinus and middle ear infections (RR
      1.9), and mastoiditis (RR 3.9). Associations with mild tinnitus included age (RR
      0.8), hearing loss (RR 1.4) and history of dizziness (RR 1.5), meningitis (RR
      2.2), and migraine (RR 1.5). Knowledge of these factors could contribute to
      improved tinnitus management.

PMID- 15239202
TI  - Effect of frequency boundary assignment on vowel recognition with the Nucleus 24
      ACE speech coding strategy.
AB  - Two speech processor programs (MAPs) differing only in electrode frequency
      boundary assignments were created for each of eight Nucleus 24 Cochlear Implant
      recipients. The default MAPs used typical frequency boundaries, and the
      experimental MAPs reassigned one additional electrode to vowel formant regions.
      Four objective speech tests and a questionnaire were used to evaluate speech
      recognition with the two MAPs. Results for the closed-set vowel test and the
      formant discrimination test showed small but significant improvement in scores
      with the experimental MAP. Differences for the Consonant-Vowel Nucleus-Consonant
      word test and closed-set consonant test were nonsignificant. Feature analysis
      revealed no significant differences in information transmission. Seven of the
      eight subjects preferred the experimental MAP, reporting louder, crisper, and
      clearer sound. The results suggest that Nucleus 24 recipients should be given an
      opportunity to compare a MAP that assigns more electrodes in vowel formant
      regions with the default MAP to determine which provides the most benefit in
      everyday life.

PMID- 15239203
TI  - Simulated conductive hearing loss in children.
AB  - Otitis media with effusion (OME) often results in hearing loss for children with
      the condition. In order to provide appropriate and effective audiologic
      management, it is important to understand the impact of OME on speech recognition
      ability when hearing loss is present. This study examined the speech recognition
      abilities of normal-hearing six- and seven-year-old children (n = 12) and adults
      (n = 12) using monosyllabic words and nonsense syllables presented at two levels
      of simulated conductive hearing loss characteristic of OME. Average speech
      recognition scores decreased as the degree of simulated conductive hearing loss
      increased. Both age groups scored significantly poorer for nonsense syllables
      than for monosyllabic words. In general, the children performed more poorly than
      the adults with the exception of the easiest listening condition for word
      stimuli. Furthermore, children appeared less able than adults to use their
      knowledge of familiar words to improve performance. These findings suggest that
      rehabilitative strategies may best be focused on combining familiarization
      techniques and amplification options.

PMID- 15239204
TI  - Analysis of prefitting versus postfitting hearing aid orientation using the
      Glasgow Hearing Aid Benefit Profile (GHABP).
AB  - Results of this study demonstrate the advantages of both pre- and postfitting
      hearing aid orientation (HAO) sessions. This study demonstrated that HAO
      counseling is helpful in expediting hearing aid benefit and satisfaction through
      the education of our clients and that this benefit and satisfaction is age
      dependent as measured by the Glasgow Hearing Aid Benefit Profile (GHABP)
      (Gatehouse, 1997). Patients with greater initial disability, as identified by
      item 1 of the GHABP, receive significant benefit from prefitting and/or
      postfitting counseling as compared to patients receiving no counseling.
      Implications of these findings are discussed.

PMID- 15239205
TI  - Functional and anatomical correlates of impaired velocity storage.
AB  - Velocity storage (VS), a brainstem function, extends the low-frequency response
      of the vestibular system. To better understand VS mechanisms and characteristics
      in humans, we analyzed retrospectively functional measures of gait,
      electrophysiological measures of vestibular function, and imaging studies in an
      attempt to determine clinical, electrophysiological, and anatomical correlates of
      abnormalities in VS. Two cohorts of patients referred to our Risk of Falls
      Assessment Clinic participated in this investigation. Group 1 (control) patients
      demonstrated normal caloric and rotary chair tests. Group 2 patients with
      impaired velocity storage (experimentals) differed clinically from Group 1 only
      by demonstrating abnormal multifrequency vestibulocular reflex phase measures on
      rotational testing. Results showed that Group 2 patients had greater impairments
      in postural stability and gait than Group 1 patients. Additionally, 80% of
      patients in Group 2 and none in Group 1 showed pontine hyperintense lesions on
      MRI.

PMID- 15239206
TI  - The development of oxytocic drugs in the management of postpartum haemorrhage.

PMID- 15239207
TI  - Changing medical doctor productivity and its affecting factors in rural China.
AB  - Using the data collected from the health facility-based survey, part of the
      national health service survey conducted in 1993 and 1998, this paper tries to
      examine changes in labour productivity among the county-level hospitals and
      township health centres in rural China, and to analyse factors affecting the
      changes. The results presented in the paper show that the average number of
      outpatient visits per doctor per day and the average number of inpatient days per
      doctor per day declined significantly over the period from 1986 to 1997. The main
      factors resulting in the reduction of productivity are associated with the
      increase of inappropriate staff recruitment in these health facilities, the
      significant decline of rural population covered by health insurance, particularly
      rural cooperative medical schemes (CMS), and the rapid rise of health care costs.
      The latter two factors also have brought about a reduction in the use of these
      health facilities by the rural population. The paper suggests that the government
      should tighten up the entrance of health and non-health staff into the rural
      health sector and develop effective measures aimed to avoid providing pervasive
      financial incentives to the over-provision of services and over-use of drugs. In
      addition, other measures that help to increase the demand for health services,
      such as the establishment of rural health insurance, should be considered
      seriously.

PMID- 15239208
TI  - The role of Taiwan's National Health Insurance program in influencing adequate
      prenatal care.
AB  - This paper reviews achievements in the utilization of prenatal care by pregnant
      women in Taiwan by analysing the 1989 and 1996 National Maternal and Infant
      Health Survey data. More precisely, it identifies and examines the programmatic
      and non-programmatic factors that influence prenatal care utilization, thus
      determining the areas that require further attention from the programe. Logistic
      regression results show that the adequacy of prenatal care use was significantly
      associated with the implementation of the National Health Insurance (NHI). A
      higher likelihood of adequate care utilization was found among women who were
      married or employed, had a higher level of education, had more experience with
      regard to pregnancy and were at higher risk in terms of obstetrics. The effect of
      facility choice showed variations after the implementation of the NHI programme.
      Prior to NHI, no differences were noted between the use of clinics and hospitals.
      After the implementation of NHI, on the other hand, women who received most of
      their care from clinics had a higher likelihood of receiving more adequate
      prenatal care than those who received care from hospitals. Regional differences
      in seeking adequate prenatal care were also evident. Mothers who were living in
      southern areas were less likely to receive adequate prenatal care despite the
      implementation of NHI. The Bureau of NHI, therefore, still needs to work on
      mechanisms to ensure that more attention is given to the distribution of its
      medical resources and that additional health care accessibility is provided to
      pregnant women in these areas.

PMID- 15239209
TI  - Popular participation and the state: democratizing the health sector in rural
      Peru.
AB  - Popular participation has been an important component of most primary health care
      strategies since the Alma Ata Declaration, 1978. This article examines the use of
      state-sponsored participation in the health sector in Peru and some of the
      experiences that have accompanied its implementation. Taking the Local Health
      Administration Committees (CLAS) from the second Fujimori government (1995-2000)
      as an example, it is shown that for self-motivated rural communities to work in
      harmony with the state, there must be willingness to adapt to the varying levels
      of intra-community differences, social integration and social support.

PMID- 15239210
TI  - Informal payment for health care and the theory of 'INXIT'.
AB  - Informal payments are known to be widespread in the post-communist health care
      systems of Central and Eastern Europe. However, their role and nature remains
      contentious, with the debate characterized by much polemic. This paper steps back
      from this debate to examine the theoretical basis for understanding the
      persistence of informal payments. The authors develop a cognitive behavioural
      model of informal payment, which draws on the theory of government failure and
      extends Hirschman's theory of 'exit, voice, loyalty', the behavioural responses
      to 'decline in firms, organizations and states'. It is argued that informal
      payment represents another possible behavioural reaction: 'inxit', which becomes
      important when the channels of exit and voice are blocked. The theory is applied
      to explain informal payments in Hungary, but can be shown to be relevant to other
      countries facing similar issues. The paper examines the proposed policies to
      tackle informal payments, and on the basis of the theory of 'inxit' it advocates
      that solutions should contain an appropriate balance between exit and voice to
      optimize the chances of maintaining a good standard of public services.

PMID- 15239211
TI  - Group work in a Dutch home care organization: does it improve the quality of
      working life?
AB  - Home care in The Netherlands is facing a trend towards increasing workloads,
      giving it the image of an unattractive sector to work in. To deal with increasing
      workloads and their effects, many solutions have been developed, including the
      concept of team or group work. This paper will address the possibilities,
      conditions and effects involved in the implementation of group work in home care
      as a means of improving the quality of working life (QWL) in this sector. To this
      end I have studied QWL in three jobs in two organizations for home care, one of
      which implemented group work. This comparison concludes that jobs in the team
      based organization are more complete and challenging, bringing more job decision
      latitude, but also higher work pressure.

PMID- 15239212
TI  - Health service quality and users' perceptions in West Nile, Uganda.
AB  - Save the Children (UK) has been working in health in the West Nile region of
      Uganda since 1980. Between 2000 and 2002, a number of operational research
      studies have been conducted which shed light on patient perceptions of the
      quality of services, of barriers to access and utilization patterns. These are
      brought together in this paper. They show that despite considerable progress in
      rebuilding infrastructure, training staff and investing in health systems in
      these districts, there is still a long way to go to provide services of an
      acceptable quality to users.

PMID- 15239213
TI  - Prognostic significance of beta-catenin nuclear expression in hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: There have been a few clinical reports about beta-catenin
      nuclear expression for hepatocellular carcinoma patients. However, the clinical
      significance of the nuclear expression has not been fully elucidated and remains
      to be controversial. METHODOLOGY: We performed immunohistochemical examinations
      using an anti-beta-catenin monoclonal antibody for 101 hepatocellular carcinoma
      patients who underwent curative hepatic resection. Background factors and the
      disease-free survival were compared between hepatocellular carcinomas with and
      without beta-catenin nuclear expression. The prognostic factors influencing
      disease-free survival were examined by univariate and multivariate analyses.
      RESULTS: Beta-catenin nuclear expression was judged as positive in 24 (23.8%) and
      negative in 77 (76.2%). Representative 3 hepatocellular carcinomas with beta
      catenin nuclear expression showed the protein accumulation by Western blotting
      analysis. The clinicopathological analysis proved that vascular invasion was less
      prevalent in hepatocellular carcinomas with beta-catenin nuclear expression than
      in those without the expression (p=0.034). Hepatocellular carcinoma patients with
      beta-catenin nuclear expression had a longer disease-free survival than patients
      without the expression (p=0.035). Multivariate analysis proved that beta-catenin
      nuclear expression was selected as one of the independent factors related to
      disease-free survival (p=0.0054). CONCLUSIONS: Our study demonstrated that beta
      catenin nuclear expression is valuable as a prognostic factor for hepatocellular
      carcinoma patients who underwent hepatic resection.

PMID- 15239214
TI  - Retroperitoneoscopic laparoscopic distal pancreatectomy with spleen salvage.
AB  - BACKGROUND/AIMS: Laparoscopic pancreatic surgery has now developed as a clinical
      practice. In urological surgery, direct extraperitoneal surgery has become
      popular in laparoscopic adrenalectomy and nephrectomy. As the pancreas is also an
      organ located in the retroperitoneal cavity, we evaluate the efficacy of
      retroperitoneoscopic laparoscopic distal pancreatectomy. METHODOLOGY: Specific
      pathogen-free Large Yorkshire pigs were studied. No major bleeding episodes were
      encountered. After carbon dioxide insufflation, the abdominal viscera were
      inspected with a laparoscope. Below the left costal convexity, the balloon
      dissector was introduced and the second port was inserted in the retroperitoneal
      cavity. The scope was inserted using that port and additional two ports were
      inserted into the retroperitoneal cavity. RESULTS: The tail to body of the
      pancreas were easily mobilized from the retroperitoneum. The identified splenic
      artery and vein were carefully isolated from the pancreas. After lap-disk was
      applied to a 4-cm incision, the tail of the pancreas was pulled out to resect
      using various devices. The cut surface of the pancreas resected with ultrasonic
      dissector showed a less damaged area than that with monopolar electrocautery and
      bipolar electrocautery. CONCLUSIONS: Retroperitoneoscopic laparoscopic distal
      pancreatectomy is a rational procedure and is safe. As the pancreatic parenchyma
      has greater water content, the devices of ultrasonic dissector seem to be
      helpful.

PMID- 15239215
TI  - Expression of receptor for advanced glycation end products (RAGE) and MMP-9 in
      human pancreatic cancer cells.
AB  - BACKGROUND/AIMS: Amphoterin is considered as a regulator for the ability of
      invasion and migration in tumor cells and embryonic neurons through binding to
      receptor for advanced glycation end products (RAGE), a multiligand cell surface
      molecule of the immunoglobulin superfamily. As matrix metalloproteinase-9 (MMP-9,
      gelatinase B) has been reported to play a critical role in tumor progression and
      metastasis, we have examined the relation of RAGE and MMP in human pancreatic
      cancer. METHODOLOGY: Three representative human pancreatic carcinoma cells were
      rendered for the study which show different metastatic potential, PANC-1 and MIA
      PaCa-2 as the cells with high ability, BxPC-3 as with low. The expression of RAGE
      was examined by RT-PCR. The expression of MMP-9 protein was examined by Western
      blotting. RESULTS: RAGE was strongly expressed in MIA PaCa-2 and PANC-1 that have
      high metastatic ability. On the contrary, RAGE was expressed little in BxPC-3
      that has low ability. Similarly, expression of MMP-9 showed almost the same
      tendency. RAGE and MMP-9 are expressed concordant with the metastatic ability of
      the human pancreatic cancer cells. CONCLUSIONS: Control of these molecules could
      be a key to regulating the metastatic ability of pancreatic cancer and this may
      be exploited in targeted therapy of this cancer.

PMID- 15239216
TI  - Closure of the cystic duct during laparoscopic cholecystectomy with a new
      feedback-controlled bipolar sealing system in case of biliary obstruction--an
      experimental study in pigs.
AB  - BACKGROUND/AIMS: The excellent results of new devices like the new bipolar
      feedback-controlled sealing system (LigaSure) for closure of blood vessels
      encouraged surgeons to use these instruments for other structures like bile
      ducts. The aim of this study was to evaluate the feasibility of closure of cystic
      duct in case of biliary obstruction. METHODOLOGY: Ten domestic pigs underwent
      laparoscopic cholecystectomy sealing the cystic duct with LigaSure. The common
      bile duct was closed with an endoclip to create a biliary hypertension. On the
      12th postoperative day blood samples were taken for liver enzymes. At autopsy on
      day 15 the pigs were investigated for bile leaks or biliary peritonitis. The
      cystic duct was resected for histological examination. RESULTS: Seven pigs
      survived, one pig died during introduction of anesthesia, one on the 1st and one
      on the 2nd postoperative day without any findings at the autopsy. One pig out of
      7 had a bile leak; the other 6 were without any sign of leakage. Histologically 3
      pigs had a regular coagulation zone at the cystic duct, 3 had a total necrosis,
      one a partial necrosis of the mucosa only. CONCLUSIONS: Though there was only one
      insufficiency, the feedback-controlled bipolar vessel sealer cannot be
      recommended for biliary surgery with regard to the high rate of necrosis stated
      in our experiment.

PMID- 15239217
TI  - Personal experience of laparoscopic cholecystectomy.
AB  - BACKGROUND/AIMS: We performed laparoscopic cholecystectomy with a surgical team
      consisting of the same operator and the same first assistant to evaluate a
      personal learning curve of laparoscopic cholecystectomy. METHODOLOGY: In the 135
      patients who underwent the laparoscopic cholecystectomy, operative complications,
      postoperative complications and operative time were evaluated on the basis of
      using different camera assistants and the chronological advancement of the same
      operator and the same first assistant. RESULTS: The average operative time was
      120 +/- 54 minutes. The operative time was statistically longer in the first ten
      cases. The major complication during operation, which was ligation of the common
      bile duct, occurred in the 7th case. The other operative complications, such as
      minor bile duct injury or mild bleeding, occurred occasionally in spite of
      experience or inexperience; the operative complications, however, tended to occur
      under the same camera assistant. On the other hand, the operative time was not
      related to the use of different camera assistants. CONCLUSIONS: From the personal
      learning curve of laparoscopic cholecystectomy, operative time is relatively
      longer in the early 10 cases. Complications tend to occur under the same camera
      assistant.

PMID- 15239218
TI  - No prognostic significance of antimitochondrial antibody profile testing in
      primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: The rate of disease progression varies considerably between
      individuals with primary biliary cirrhosis (PBC). On the basis of serological
      subtyping 4 antimitochondrial antibody (AMA) profiles (A, B, C and D) can be
      defined. The finding of previous studies that profile C/D is associated with a
      progressive course, in contrast to profile A/B, is a question of debate. The aim
      of the study was to investigate whether AMA profiles predicted the course for a
      cohort of Dutch PBC patients. METHODOLOGY: Patients with an established diagnosis
      of AMA-positive PBC, AMA-negative PBC patients, non-PBC decompensated cirrhotics
      and healthy volunteers. Serum samples from 38 AMA-positive progressive patients,
      31 AMA-positive patients without evidence of progression for at least 6 years, 5
      AMA-negative PBC patients, 5 non-PBC decompensated cirrhotics and 5 healthy
      volunteers were assessed. AMA profiles were determined without knowledge of the
      clinical data. RESULTS: In the progressive AMA-positive group, 13% had profile
      A/B and 84% had profile C/D. In the non-progressive group, 13% had profile A/B,
      77% profile C/D; 10% had no profile. During follow-up, a change from profile A/B
      to profile C/D or vice versa was not observed. CONCLUSIONS: This study found that
      not only PBC patients with AMA profile C/D but also patients with profile A/B may
      run a progressive course and therefore does not support the suggestion that AMA
      profiles can be used as independent prognostic indicator. The divergent results
      of this and previous studies may be explained by the selection of different
      patient populations.

PMID- 15239220
TI  - Risk factor for extrahepatic bile duct cancer in patients with anomalous
      pancreaticobiliary ductal union.
AB  - BACKGROUND/AIMS: Anomalous connection between the choledochus and pancreatic duct
      is considered to be a factor in the development of biliary tract diseases such as
      choledochal cyst, pancreatitis, cholangitis, gallbladder cancer, and bile duct
      cancer. Our purpose was analysis of combined disease, especially biliary neoplasm
      and evaluated microscopic changes of extrahepatic bile ducts. METHODOLOGY: To
      study the clinical characteristics of anomalous pancreaticobiliary ductal union
      (APBDU), we reviewed 14 APBDU cases from June 1994 to June 1998. We studied the
      associated disease, surgical treatment, and the histological findings of the
      extrahepatic bile ducts. RESULTS: Gallbladder cancer was identified in 5 out of
      14 patients with APBDU. The incidences of metaplasia of gallbladder and bile duct
      with APBDU were higher than that of control gallbladder epithelium. The
      proliferating cell nuclear antigen-labeling index of the gallbladder in patients
      with APBDU was significantly higher than that in the control group. CONCLUSIONS:
      The patients with APBDU showed high incidence of gallbladder carcinoma and
      metaplasia in epithelium of gallbladder and bile duct. As this metaplasia in the
      gallbladder and bile duct is thought of as a precancerous condition, it is
      important to remove the place that causes bile stasis and to stop backflow of
      pancreatic juice into the bile duct in managing patients with this anomaly. In
      other words, prophylactic cholecystectomy and reconstruction of the biliary tract
      are both necessary.

PMID- 15239219
TI  - Ceftriaxone is twice as cost-effective as standard therapy in biliary tract
      infection.
AB  - BACKGROUND/AIMS: Various antibiotics, mainly cephalosporins and broad-spectrum
      penicillins, are indicated in biliary tract infection. The primary endpoint was
      to compare the cost-effectiveness of ceftriaxone (Rocephin) 1 g once daily vs.
      standard therapy two or three times daily. METHODOLOGY: A prospective multicenter
      observational study, matched-pair analysis of 902 patients receiving ceftriaxone
      or standard therapy (second-generation cephalosporin, broad-spectrum penicillin
      or a combination of aminopenicillin and beta-lactamase inhibitor) in 75 hospitals
      yielded 173 pairs matched for definite risk criteria. Both groups received
      comparable accompanying endoscopic antiobstructive treatment. Cost parameters
      included primary antibiotic purchase, total antibiotic purchase (including
      combination and second-line drugs), and infusion preparation and administration.
      RESULTS: 87.9% of patients in the ceftriaxone group vs. 73.4% in the standard
      group received antibacterial monotherapy, for 7.5 vs. 9.1 days respectively
      (p=0.001). Therapy was equally effective in both groups. Overall treatment costs,
      including antibiotic purchase and infusion preparation/administration, were
      170.84 vs. 320.46, respectively (p=0.0001). CONCLUSIONS: Ceftriaxone 1 g once
      daily is approximately twice as cost-effective as standard therapy in biliary
      tract infection: lower concomitant medication costs, a shorter treatment course,
      and lower antibiotic administration costs achieved an approximate 50% saving.

PMID- 15239221
TI  - Laparoscopic cholecystectomy in patients with porcelain gallbladder based on the
      preoperative ultrasound findings.
AB  - BACKGROUND/AIMS: Porcelain gallbladder is considered a relative contraindication
      to laparoscopic cholecystectomy, because of a high incidence of gallbladder
      cancer or gastrointestinal cancer. We examined the management of laparoscopic
      cholecystectomy in patients with porcelain gallbladder. METHODOLOGY: 1,608
      patients underwent cholecystectomy and 13 (0.81%) patients had porcelain
      gallbladder. All patients underwent preoperative spiral computed tomography after
      intravenous infusion cholangiography and intraoperative cholangiography. Patients
      with porcelain gallbladder were classified as Type I to III according to
      preoperative ultrasound findings. The Type I porcelain gallbladder was indicated
      for laparoscopic cholecystectomy and Type II porcelain gallbladder was selected
      for open cholecystectomy. RESULTS: The laparoscopic cholecystectomy was completed
      in 10 patients with Type I porcelain gallbladder and the microscopie diagnosis
      demonstrated no cancer in the calcified wall of the gallbladder. In one patient
      with a non-transected injury to the right hepatic duct, a T-drainage tube was
      inserted at the site of the injury using the laparoscopic technique. Three
      patients with Type II porcelain gallbladder underwent open cholecystectomy and
      one patient had gallbladder cancer, therefore additional hepatectomy and
      lymphadenectomy was performed. CONCLUSIONS: We conclude that patients with a Type
      I porcelain gallbladder should be considered for laparoscopic cholecystectomy
      using a preoperative selection based on the ultrasound findings.

PMID- 15239222
TI  - Relief of jaundice by external beam radiotherapy and intraluminal brachytherapy
      in patients with extrahepatic cholangiocarcinoma: results without stenting.
AB  - BACKGROUND/AIMS: To clarify whether external beam radiotherapy combined with
      intraluminal brachytherapy without stenting provides long-term relief of jaundice
      in extrahepatic cholangiocarcinoma patients. METHODOLOGY: Twenty-five patients
      with unresectable hilar or distal cholangiocarcinoma were treated by external
      beam radiotherapy (30 or 50 Gy) combined with intraluminal brachytherapy (24 to
      40 Gy). After radiotherapy, we removed the biliary drainage tubes from the
      patients who responded, and we did not perform stenting in these patients.
      RESULTS: In 19 (76%) patients, full patency was achieved at the treated lesion,
      and they were tube-free thereafter. The tube-free survival time in the 19
      patients ranged from 7 to 468 days (median: 76 days). Cholangitis and
      gastroduodenal ulcer developed in 10 (40%) and 2 (8%) patients, respectively, as
      adverse events after the combined radiotherapy. The median survival time of all
      patients was 9.3 months, and their 6- and 12-month survival rates were 75.3% and
      29.3%, respectively. The ratios of tube-free to overall survival in the 19
      patients ranged from 2.4% to 79.4% (median: 26.8%). Eight patients died tube
      free. CONCLUSIONS: Although there were limitations to the long-term relief of
      jaundice by this combined radiotherapy alone, tube-free status was achieved in
      some patients without stenting.

PMID- 15239223
TI  - Case report: laparoscopic cholecystectomy in situs viscerum inversus.
AB  - Situs viscerum inversus is a rare condition, in which the organs are transposed
      from their normal location in the opposite side of the body. The inversion of L-R
      asymmetry may be complete (SVI totalis) or partial (SVI partialis), whereby
      transposition is confined to either the abdominal or thoracic viscera. The
      authors report a case of videolaparocholecystectomy for cholelithiasis
      successfully performed on a 41-year-old Caucasian woman with situs viscerum
      inversus totalis. The patient was discharged on the 2nd postoperative day. The
      symptomatology disappeared right after the intervention, and still now, after a
      follow-up of six months, is absent. The procedure was safely performed on the
      patient with no particular difficulties, except for the reverse position of the
      angle between the operating and exposing trocars, which led to a difficult
      approach to the Calot triangle when using the right hand of the surgeon.

PMID- 15239224
TI  - A localized primary sclerosing cholangitis preoperatively diagnosed as hilar
      cholangiocarcinoma; report of a case.
AB  - The authors report herein a case of primary sclerosing cholangitis localized to
      the hepatic hilum which occurred in a 67-year-old male. The direct
      cholangiography revealed bile duct stenosis from the common hepatic duct to
      bilateral hepatic ducts. We could not confirm bile duct malignancy, however,
      hilar cholangiocarcinoma was most suspicious. We performed right trisegmentectomy
      of the liver with caudate lobectomy and lymph node dissection 3 weeks after right
      portal embolization. Pathological findings confirmed localized primary sclerosing
      cholangitis. Surgical resection of the affected bile duct is most effective in
      localized primary sclerosing cholangitis, because the prognosis of the disease is
      poor and secondary carcinogenesis in primary sclerosing cholangitis has high
      incidence.

PMID- 15239225
TI  - Prognostic value of micrometastases in esophageal and colorectal carcinoma (a
      clinical experience).
AB  - BACKGROUND/AIMS: The term "micrometastases" has been confused in many aspects.
      While the influence of lymph node metastases in esophageal and colorectal cancer
      is well known, the presence and importance of micrometastases is under debate. We
      investigated micro lymph node invasion in two different kinds of digestive tumors
      with very high mortality, and identified its possible repercussion on patient
      survival. METHODOLOGY: Lymph nodes of two groups of patients N0 on routine
      histopathology after radical resection (R0): 21 with esophageal carcinoma (Group
      I), and 21 with colorectal carcinoma (Group II), were studied by
      immunohistochemistry using monoclonal antibodies directed against cytokeratins of
      wide spectrum. The results were classified as positive or negative and compared
      with patient survival. RESULTS: Five of twenty-one (5/21) patients in group I and
      eight of twenty-one (8/21) in group II were positive for micrometastases. Median
      survival time in the positive esophageal group was 9.5 months vs. 68 in the
      negative one (p=0.16). Median survival time in the positive subset colorectal
      group was 54.5 months vs. 76.8 in the negative subgroup (p=0.5). Our results did
      not show statistical differences in survival time between patients positive or
      negative for micrometastases; however it is evident, especially in the esophageal
      cancer group, that there is a negative tendency of positive micrometastases on
      survival time. CONCLUSIONS: The presence of micrometastases in lymph nodes of
      patients N0 after conventional histopathology is frequent. Our preliminary
      results did not allow definitive conclusions but we may suppose its negative
      influence on patient survival.

PMID- 15239226
TI  - Short-term interferon therapy for chronic hepatitis C patients with low viral
      load.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of high-dose short-term interferon
      therapy prospectively in 32 chronic hepatitis C patients with a low viral load
      showing the rapid disappearance of hepatitis C virus RNA after the start of
      interferon therapy. METHODOLOGY: Each patient was confirmed with a low hepatitis
      C virus RNA level less than 1.0 Meq/mL before the start of interferon therapy
      regardless of hepatitis C virus genotypes. High-dose short-term interferon
      therapy was defined as administration of natural interferon alpha 10 MU/day for
      14 weeks (daily for 4 weeks then three times a week for 10 weeks). This course of
      treatment was carried out only in cases with the rapid disappearance of hepatitis
      C virus RNA at 2 weeks after the start of interferon. RESULTS: Sustained
      virological response was observed in 30 of 32 patients (93.8%) who received high
      dose short-term interferon therapy. One patient who received 24 weeks interferon
      administration relapsed and became a non-responder. One patient refused to
      continue this therapy. CONCLUSIONS: High-dose short-term interferon therapy might
      be useful when combining the selection of patients according to pretreatment
      hepatitis C virus RNA levels and testing virus presence at an early point after
      the start of interferon therapy.

PMID- 15239227
TI  - Surgical anatomy of arteries running transversely in the pancreas, with special
      reference to the superior transverse pancreatic artery.
AB  - BACKGROUND/AIMS: In pancreatic surgery, the pancreas is usually divided over the
      portal vein. Knowledge of transversely oriented arterial systems within the
      pancreas that would need to be ligated in most forms of pancreatic surgery is
      clinically important. We studied the anatomy of arteries running transversely in
      the pancreas. METHODOLOGY: Thirty-eight cadavers donated for education and
      research were examined. The parenchyma of the pancreas was removed gradually from
      both the ventral and dorsal sides to reveal these arteries. Arteries at least 0.5
      mm in diameter were sketched and counted. RESULTS: The mean number of divided
      arteries over the portal vein at least 0.5 mm in diameter per specimen was 2.5 +/
      1.1 (range 1 to 5). The divided arteries were mainly transverse pancreatic (TP),
      superior TP, and dorsal pancreatic (DP) arteries. The superior TP artery was
      observed in 24/38 specimens (63.2%) and ran along the superior ventral side of
      the head of the pancreas in 79.2% of specimens. The superior TP artery was formed
      between the gastroduodenal (GD) and DP arteries in 15/38 specimens (39.5%). In
      pancreatic surgery, surgeons need to be aware of the anatomy of the superior TP
      artery. The TP artery usually originated from the GD artery and its branches. The
      TP artery joined with the DP artery in 61.3% of specimens and ran along the
      inferior surface of the body and tail of the pancreas. The TP artery frequently
      anastomosed with the great pancreatic artery. Arterial catheters for continuous
      delivery of protease inhibitors in acute necrotizing pancreatitis should be
      placed into the GD artery, because this will achieve perfusion of the entire
      pancreatic parenchyma. CONCLUSIONS: We termed the artery originating from the GD
      or DP arteries, located at the cranial side of the head of the pancreas, the
      superior TP artery. Surgeons should pay close attention to the anatomy of the
      superior TP artery during pancreatic surgery.

PMID- 15239228
TI  - Refractory proctosigmoiditis probably caused by inferior mesenteric vein ligation
      at sigmoidectomy.
AB  - A case of refractory proctosigmoiditis is reported in a 65-year-old female post
      sigmoidectomy patient. She had bloody diarrhea and abdominal pain 2 years after
      sigmoidectomy, in which the inferior mesenteric vein was ligated close to the
      inferior mesenteric artery root during the lymph node dissection, while the
      inferior mesenteric artery trunk and the last branch of the sigmoid arteries was
      preserved. The biopsied specimen obtained by a fiber optic colonoscopy was
      diagnosed as proctitis. Antidiarrheals, 5-aminosalicylic acid and steroid enemas
      showed only limited therapeutic effects. An angiography revealed a mild degree of
      rectal artery dilatation and tiny venous angiogenesis detected on the delayed
      phase images. Because the inferior mesenteric vein had been ligated, collateral
      veins developed to drain the blood on the distal side of the anastomosis to
      bilateral internal iliac veins. The venous blood of the descending colon (oral
      side of anastomosis) drained to left colic vein. The cause of rectosigmoiditis
      was considered to be venous congestion due to the inferior mesenteric vein
      ligation. A rectosigmoidectomy with reanastomosis using a double-stapling
      technique was performed, and the patient was discharged without symptoms.

PMID- 15239229
TI  - A case of primary mesenteric embryonal carcinoma.
AB  - We describe a case of primary mesenteric embryonal carcinoma. The patient was a
      73-year-old man who presented with a huge mass palpable at the right upper side
      of the abdomen. Laboratory evaluations showed very high alpha-fetoprotein and
      PIVKA-II levels, and an abdominal computed tomographic scan demonstrated a mass
      contiguous with the liver. These findings suggested hepatic cell carcinoma
      extending beyond the liver. However, angiography showed the mass to be supplied
      mainly by the middle colic artery and greater omentum artery, suggesting a
      mesenteric tumor. Gastroscopy demonstrated a IIc lesion in the anterior wall of
      the antrum. This lesion was histologically diagnosed to be moderately
      differentiated adenocarcinoma. The large tumor adjacent to the liver was
      diagnosed to be a primary mesenteric tumor or a metastatic mesenteric tumor from
      arising gastric cancer. At laparotomy, a huge tumor was found in the gastrocolic
      ligament. The tumor adhered to the distal part of stomach, the transverse colon,
      and the gallbladder. En-bloc resection of the tumor was performed, including the
      distal part of stomach, Part of the transverse colon, and the gall-bladder. The
      tumor mass measured 26.0 x 21.0 x 9.0 cm, weighted 2750 g, and showed central
      necrosis and hemorrhage. The histopathological diagnosis was a primary embryonal
      carcinoma originating in the mesentery. Primary mesenteric embryonal carcinoma is
      extremely rare. To our knowledge, no other cases have been reported. We describe
      this case and briefly discuss the related literature.

PMID- 15239230
TI  - Intraoperative massive pulmonary tumor embolism from clear cell sarcoma in the
      retroperitoneum: successful treatment using cardiopulmonary bypass.
AB  - Malignant neoplasms rarely extend into the inferior vena cava and up to the right
      side of the heart. Although massive pulmonary tumor embolism occurs relatively
      rarely, it can be a catastrophic problem. Intraoperative pulmonary tumor embolism
      and cardiac arrest occurred in a 68-year-old woman while dissecting the inferior
      vena cava to resect a pararenal tumor extending into the retrohepatic inferior
      vena cava. Abrupt arterial hypotension, tachycardia, and increased central venous
      pressure lead to the diagnosis of massive pulmonary tumor embolism. Emergency
      cardiopulmonary bypass was commenced under profound hypothermia and cardiac
      arrest. The tumors in the main pulmonary artery were extracted, and fragments of
      remnant tumor were retrieved by a vascular endoscope, a Fogarty catheter, and
      milking of the lung. Following embolectomy, the tumor in the retrohepatic to
      infrarenal inferior vena cava was removed and the primary tumor together with the
      infrarenal inferior vena cava was resected under hepatic vascular exclusion and
      partial cardiopulmonary bypass. The inferior vena cava below the renal veins was
      not reconstructed. The patient recovered with slight retrograde amnesia. A
      postoperative pulmonary perfusion scintigram showed no defect in the pulmonary
      circulation. She is well now 8 months after surgery. Safe prevention measures
      should be accomplished as a part of the perioperative management of patients with
      inferior vena cava tumor thrombus that may be fragile, and cardiopulmonary bypass
      should always be stand-by on surgery.

PMID- 15239231
TI  - Usefulness of bipolar scissors for rectal cancer surgery with autonomic nerve
      preservation.
AB  - BACKGROUND/AIMS: Pelvic autonomic nerve preservation for rectal cancer has become
      more common in recent years. Therefore, we evaluated the usefulness of bipolar
      scissors for this procedure. METHODOLOGY: This study included 30 consecutive
      patients with lower rectal cancer who underwent pelvic autonomic nerve
      preservation at our hospital between April 1998 and August 2001. The bipolar
      scissors group comprised 10 patients who received the procedure using bipolar
      scissors, while the conventional group included 20 patients who received the
      procedure without the use of bipolar scissors. The two groups were compared in
      terms of operating time, blood loss, postoperative urinary and sexual function.
      RESULTS: Blood loss in the bipolar scissors group was 394.4 +/- 201.8mL, which
      was a significantly lower volume than that in the conventional group (881.8 +/-
      582.9ml) (p=0.0049). All the patients in the bipolar scissors group (10/10=100%)
      and 19 cases in the conventional group (19/20=95.0%) answered that they were
      satisfied with the results of their voiding function. In the bipolar scissors
      group, 100% were capable of erection (5/5) and 80.0% preserved ejaculation (4/5).
      In the conventional group, 100.0% (10/10) and 77.8% (7/9) preserved erection and
      ejaculation, respectively. CONCLUSIONS: The use of bipolar scissors is quite
      beneficial when patients with rectal cancer receive pelvic autonomic nerve
      preservation.

PMID- 15239232
TI  - Effect of leptin on healing of colonic anastomoses in rats.
AB  - BACKGROUND/AIMS: Anastomotic leaks are continuing to be the source of major
      morbidity in colorectal surgery. Previous studies have shown that leptin acts as
      a growth factor for several cell types. The aim of this study was to evaluate the
      effect of leptin on healing of colonic anastomoses in rats. METHODOLOGY: Forty
      eight rats were divided into 5 groups. Group I (n=8) sham; group II (n=10)
      control; right colonic anastomosis, group III (n=10); following right colonic
      anastomosis, treated with leptin twice-daily 1 mg/kg intraperitoneally, group IV
      (n=10); before right colonic anastomosis, 45 min of colonic ischemia has been
      created, group V (n=10); following 45 min of colonic ischemia and right colonic
      anastomosis, leptin was given twice-daily 1 mg/kg intraperitoneally. On the 7th
      postoperative day relaparotomy was performed. Bursting pressure (BP), tissue
      hydroxyproline concentrations (THPC), and histopathologic properties of
      anastomoses; vascular tissue proliferation (VTP), collagen tissue proliferation
      (CTP), polymorphonuclear leukocyte infiltration (PMNLI), mononuclear leukocyte
      infiltration (MNLI) were analyzed and results were compared statistically.
      RESULTS: BP and THPC were found to be significantly higher in group III and group
      V in comparison with group II and group IV respectively (P<0.05).
      Histopathologically, leptin significantly increased VTP, CTP, MNLI (P<0.001), and
      significantly decreased PMNLI (p<0.05) on non-ischemic and ischemic colonic
      anastomoses. CONCLUSIONS: Leptin can be used safely in colorectal surgery since
      it accelerates the healing of colonic anastomoses.

PMID- 15239233
TI  - The risk of lymph node metastasis in T1 colorectal carcinoma.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the risk of lymph node
      metastasis in patients with T1 colorectal carcinoma based on a uniform
      histopathology system, and to accomplish guidelines for additional surgery for
      endoscopically or locally removed T1 colorectal carcinoma. METHODOLOGY: A review
      was performed of 301 patients who underwent curative resection for T1 colorectal
      carcinoma between January 1970 and March 2001. The following clinicopathologic
      variables were evaluated using univariate and multivariate analysis: sex, age,
      location, size of tumor, macroscopic appearance, depth of submucosal invasion,
      lymphovascular invasion, and histologic grade. Lesions were subdivided according
      to the depth of submucosal invasion: sm1, submucosal invasion up to 500 microm
      from the muscularis mucosa; sm2, submucosal invasion between 500 and 1000 microm;
      sm3, submucosal invasion beyond 1000 microm. RESULTS: The overall lymph node
      metastasis rate was 6.3 per cent (19 of 301). Depth of submucosal invasion (sm3)
      and presence of lymphovascular invasion were significant risk factors for lymph
      node metastasis both univariately and multivariately. CONCLUSIONS: The findings
      of the current study demonstrated that significant risk factors for lymph node
      metastasis were level of submucosal invasion (sm3) and the presence of
      lymphovascular invasion. Surgery is indicated for patients with adverse factors.

PMID- 15239234
TI  - Immunoreactivity evaluation of mutant p53 gene product with DNA ploidy pattern in
      colorectal carcinoma.
AB  - BACKGROUND/AIMS: Studying p53 protein expression in tumor cells is one of the
      effective methods for detecting p53 gene mutations. This study attempted
      simultaneous monitoring of p53 overexpression in colon cancer using
      immunohistochemical and immunoblotting techniques and also to compare
      abnormalities of p53 with DNA ploidy and clinicopathological variables.
      METHODOLOGY: The occurrence of p53 protein expression was analyzed in forty-nine
      fresh colorectal cancer specimens by immunohistochemical and p53 protein
      expression also demonstrated by Western immunoblotting technique in 28 colorectal
      cancer specimens, using an anti-human p53 monoclonal antibody (Do-7), and 25
      normal colon mucosa as a negative control. DNA ploidy in 36 specimens of colon
      cancer tissues was determined by Flow cytometry. RESULTS: Overexpression of p53
      protein was detected immunohistochemically in 53.1% (26 of 49) of the tumor
      specimens. DNA ploidy was performed in 36 cases, 55.6% (20 of 36) of colon cancer
      specimens were DNA aneuploidy, p53 immunostaining was positive in 60% of cases
      with DNA aneuploidy compared to 31.3% in diploid tumors (p<0.001). There was no
      significant association between p53 immunostaining and clinicopathological
      variables. Overexpression of p53 protein was demonstrated in nuclear protein
      extract by immunoblotting in 75% (21 of 28) of colorectal carcinoma. Aneuploidy
      carcinomas were more frequently p53 positive by immunoblotting than DNA diploidy
      carcinomas; 76.5% (13 of 17) vs. 72.7% (8 of 11) (p<0.2). P53 expression by
      immunoblotting was more frequently found in good lymphocytic infiltration than
      moderate and poor lymphocytic infiltration (p<0.001). Also, p53 expression in
      right colon was significant with rectum (p<0.009). The incidence of p53
      expression in Duke's stage B was significant if compared with Duke's stage C
      (p<0.005). Immuno-reactivity of p53 expression was detected by immunostaining and
      immunoblotting in 89.3% (25 of 28) of colorectal cancer. P53 immunoreactivity by
      immunostaining and immunoblotting were closely related to the clinicopathological
      variables such as pathological type (p<0.01), lymphocytic infiltration
      (p<0.0001), tumor grade, and tumor site (p<0.001). DNA aneuploidy was more
      frequently p53 positive than DNA diploid tumor by immunostaining and
      immunoblotting (p<0.001). CONCLUSIONS: Immunohistochemistry confirmed by
      immunoblotting assay is a sensitive method for detecting the trace amount of p53
      protein and provides valuable information for the understanding of colorectal
      cancer biology.

PMID- 15239235
TI  - SOFA score predicts postoperative outcome of patients with colorectal
      perforation.
AB  - BACKGROUND/AIMS: Colorectal perforation remains a life-threatening condition
      associated with high mortality. Various factors and operative procedures have
      been discussed in regard to prediction of outcome, and several scoring systems
      have been proposed to predict the outcome of critically ill patients. The present
      study was undertaken to identify factors and determine predictive scoring systems
      for the postoperative outcome of patients with colorectal perforation.
      METHODOLOGY: Between January 1996 and December 2000, 45 consecutive patients
      underwent emergency operation for colorectal perforation. Twelve patients (26.7%)
      died in hospital. The correlation of outcome with various preoperative factors,
      APACHE II and SOFA scores were assessed retrospectively. RESULTS: Univariate
      analysis showed that outcome was significantly related to maximum SOFA score
      (p=0.0069). Multivariate logistic regression analysis demonstrated that the
      maximum SOFA score was an independent predictor (p=0.016). Serum creatinine level
      (p=0.013) and platelet count (p=0.036) were associated with patient outcome in
      the SOFA score. Patients with a SOFA score higher than 7 had a greater risk of
      hospital death (p=0.0085). CONCLUSIONS: The maximum postoperative SOFA score is a
      useful predictor of the outcome from surgery for colorectal perforation.

PMID- 15239236
TI  - Gasless laparoscopy-assisted colon surgery utilizing mini-laparotomy and a
      subcutaneous abdominal wall lift system.
AB  - BACKGROUND/AIMS: This study was performed to investigate the technical aspects
      and perioperative results of using a subcutaneous abdominal wall lift system for
      laparoscopy-assisted colectomy. METHODOLOGY: We attempted a laparoscopy-assisted
      colectomy for 19 patients and completed 16 cases using mini-laparotomy and a
      subcutaneous abdominal wall lift system, observing monitor images via laparoscopy
      or direct views through mini-laparotomy. All 5 surgeons had no experience of
      laparoscopy-assisted colectomy but considerable experience of laparoscopic
      cholecystectomy. RESULTS: The operating time ranged from 120 to 360 minutes with
      an average of 188. Intraoperative blood loss ranged from 20 to 300 mL with an
      average of 116 mL. No postoperative major complications occurred, but 5 cases
      suffered wound infection. CONCLUSIONS: Laparoscopy-assisted colon surgery
      utilizing a subcutaneous abdominal wall system and mini-laparotomy was feasible
      as minimally invasive surgery for colorectal diseases, even for surgeons with
      little previous experience.

PMID- 15239237
TI  - Three-field dissection or two-field dissection?--A proposal of new algorithm for
      lymphadenectomy.
AB  - BACKGROUND/AIMS: There are no systematic criteria for cervical lymphadenectomy in
      esophageal carcinoma. We provide a new algorithm for deciding whether to use
      three-field dissection or two-field dissection. METHODOLOGY: Ninety-eight
      patients underwent curative esophagectomies with three-field lymph node
      dissections for squamous cell carcinoma of the thoracic esophagus. We examined
      the outcomes and predictors for survival of these patients. Therefore, we devised
      a new decision tree for deciding whether to use three-field dissection or two
      field dissection. RESULTS: The overall 5-year survival rate for the 98 patients
      was 41.3%. The number of positive nodes was the only significant predictor for
      survival in the multivariate Cox proportional hazard model. The outcomes of
      patients with positive supraclavicular/internal jugular nodes were poor. On the
      other hand, positive cervical paraesophageal nodes do not worsen prognosis. We
      provided a new algorithm for selecting procedure of lymphadenectomy based on the
      presence of lymph node metastases. This algorithm is decided by the number of
      positive nodes, the presence of cervical node metastasis and recurrent nerve node
      metastasis. According to this decision tree, there were a few patients who needed
      absolutely three-field dissections. CONCLUSIONS: The new algorithm may be helpful
      for deciding three-field dissection or two-field dissection for thoracic
      esophageal carcinoma.

PMID- 15239238
TI  - Ultraflex stent--benefits and risks in ultimate palliation of advanced, malignant
      stenosis in the esophagus.
AB  - BACKGROUND/AIMS: Sophisticated endoscopical palliation in end-stage malignant
      stenosis of the esophagus and gastroesophageal-junction must be weighed against
      associated morbidity and mortality. In a prospective study we investigated
      benefits and risks of one type of coated, self-expandable stent in ultimate
      palliation of esophageal neoplasms focusing on factors that might predispose
      patients to develop complications. METHODOLOGY: 33 men (70.2%) and 14 women
      (29.8%), (mean age 68.3 years, range from 38 to 90 years), suffering from
      nonresectable malignant stenosis of the esophagus due to advanced tumor stage
      and/or functional inoperability were treated by using a covered, self-expandable
      stent (covered ULTRAFLEX esophageal stent system, Microinvasive, Boston
      Scientific Corporation, Boston, MA). Stenting was indicated because of severe
      dysphagia for liquids and saliva in 41 (87.2%) patients, tracheoesophageal
      fistula in 5 (10.6%) patients and in one case of tumor bleeding (2.1%). 32 out of
      47 patients had had one or other multiple treatment modalities before stenting.
      In 15 patients stenting was the first and only therapeutic option. RESULTS: All
      patients experienced an improvement of dysphagia immediately after stenting.
      Eight out of 47 patients (17.1%) developed major stent-associated complications:
      Early complications within 4 days after implantation evolved in two cases, with
      one patient dying from stent-induced perforation with consecutive mediastinitis
      and multi-organ failure. Late complications (20 to 180 days after stent
      implantation) occurred in 6 cases: Three esophagotracheal fistulae (two with
      tracheal compression) induced by stent expansion, one stent-induced bleeding and
      two stent dislocations. After appropriate complication management all but two
      patients were able to be discharged after a mean of 2.6 days. Multivariate
      analysis did not show any factors that might have predicted the development of
      major stent-associated complications. CONCLUSIONS: Implantation of the self
      expandable Ultraflex-stent will efficiently palliate dysphagia, bleeding and
      fistulae. The 17% risk of major complications seems acceptable regarding the
      inherent problems of alternative treatment options, like gastrostomy, PEG,
      nasogastric tube or long-term parenteral feeding.

PMID- 15239239
TI  - Effective treatment with chemotherapy and surgery for advanced small cell
      carcinoma of the esophagus.
AB  - A 78-year-old man reported a persistent midthoracic pain, mild dysphagia, and an
      abdominal distention. An abdominal computed tomography scan showed massive
      ascites, extensive paracardial mass, a large mass which invaded the pancreas, and
      a mass of multiple para-aortic lymphadenopathies which involved the superior
      mesenteric artery. An upper gastrointestinal endoscopic study revealed an
      infiltrative, ulcerating tumor of the lower esophagus. Histological study of the
      biopsy specimens from esophageal tumor showed small cell carcinoma. After
      combination chemotherapy, an abdominal computed tomography scan showed a
      disappearance of asites, a partial response reduction of paragastric mass,
      peripancreatic mass and para-aortic lymphadenopathies. Histological study of the
      biopsy specimens from esophageal tumor showed a viable small cell carcinoma. In
      June 2001, the patient underwent lower esophagectomy and proximal gastrectomy
      combined with splenectomy and distal pancreatectomy through an abdominal
      approach. Histological findings of the resected specimen showed that the
      esophageal tumor was a small cell carcinoma which invaded into the submucosal
      layer, and both paracardial and peripancreatic tumors, and all lymph nodes had no
      cancer cells. The patient's postoperative recovery was uneventful and discharged
      without aggressive chemotherapy postoperatively. However, he eventually died of
      progression of the metastasis 21 months after first detection of the carcinoma.
      Patients with esophageal small cell carcinoma treated with surgery following
      chemotherapy and/or radiotherapy have been reported to survive longer than those
      treated with chemotherapy and/or radiotherapy. Therefore, surgical resection may
      be recommended as the second therapy that occasionally produces long-term
      remission and possibly long-term survival for patients with small cell carcinoma
      of the esophagus.

PMID- 15239240
TI  - Intestinal wall damage in simple ileus in rabbits: immune-modulator role of
      somatostatin.
AB  - BACKGROUND/AIMS: We aim to determine in which way the local immune system would
      be responsible for the structural changes in intestinal obstruction, and how
      these are influenced by Somatostatin, an intestinal peptide with immunomodulatory
      properties. Simple ileus causes a series of functional and anatomical changes,
      which have been related to the peptidergic neural system, and inflammatory
      mediators. These changes are reversible with the use of Somatostatin.
      METHODOLOGY: 27 rabbits divided into three groups, were subjected to the same
      procedure, in which a simple closed loop obstruction is caused by means of
      jejunum ligatures. The three groups are perfused with physiologic saline during
      24 hours post-obstruction; one of them is perfused with Somatostatin from the
      time of intervention, and other after 8 hours. Samples of the intestinal wall are
      taken for histological analysis, and of the intraluminal liquid to determine the
      tumor necrosis factor alpha, interleukin 2, interleukin 6, and serotonin.
      RESULTS: Both group treated with Somatostatin show a wall which is in good
      condition, while the untreated group showed lesions. These lesions are related to
      higher levels of tumor necrosis factor alpha, and interleukin 2, while there were
      no changes in the levels of interleukin 6. CONCLUSIONS: The Somatostatin in
      perfusion shows a cytoprotective activity in the intestinal wall, and a blockage
      of the production of mediators of cellular immunity, while humoral immunity does
      not appear to be involved in these phenomena.

PMID- 15239241
TI  - 133Xe clearance estimates the effect of vasopressin on peritoneal blood flow in
      rats.
AB  - BACKGROUND/AIMS: When assessing the peritoneal microcirculation with invasive
      methods, interference with the mechanisms of vaso-regulation may occur. The 133Xe
      clearance technique renders the possibility, by minimal invasiveness, to estimate
      the influence of a vasoactive agent on the peritoneal microcirculation.
      METHODOLOGY: Ten to 15MBq of 133Xe were injected in the abdominal cavity in
      thirty-eight Wistar-FU (W-FU) rats and 35 Lister-Hooded (LH) rats. A NaI (Tl)
      scintillation detector registered activity before and during vasopressin
      infusion. Gamma camera imaging confirmed the washout from the abdominal cavity.
      The laser Doppler flowmetry technique was used as a comparison. RESULTS:
      Vasopressin at 0.07 IU/kg/min IV significantly reduced 133Xe-clearance by 37% (p
      = 0.029) and 52% (p=0.036) and laser Doppler flowmetry by 69% (p=0.0019) and 44%
      (p=0.0039) in W-FU and LH rats, respectively. A linear correlation between dose
      of vasopressin and relative decrease in 133Xe clearance was demonstrated in the W
      FU rat model (r2=0.98, p=0.023). The 133Xe clearance from the abdominal cavity in
      rat using a single-compartment model or the slow compartment in a double
      compartment model gave reproducible information. CONCLUSIONS: The usefulness of
      this mini-invasive technique for sequential measurements before and during
      intervention will render the 133Xe clearance suitable for assessment of blood
      flow changes in the abdominal cavity.

PMID- 15239242
TI  - Histological studies on Hirschsprung's disease and its allied disorders in
      childhood.
AB  - BACKGROUND/AIMS: To obtain accurate diagnosis for Hirschsprung's disease (HD) and
      its allied disorders such as hypoganglionosis (Hypo) and intestinal neuronal
      dysplasia (IND) in childhood patients with chronic constipation, we studied the
      histology of childhood patients with refractory constipation accompanied by
      abdominal distension and pain. METHODOLOGY: Based on clinical signs and symptoms
      noted on admission, all of 109 patients (60 males and 49 females, aged 2-15 years
      with a mean age of 9.8 years) were suspected to have chronic refractory
      constipation. To obtain accurate histological diagnosis in childhood patients
      with chronic refractory constipation, we performed rectal biopsies on these
      patients. Tissue samples were frozen and 12-microm sections were stained with
      acetylcholinesterase (AChE) by the method of Karnovsky and Roots, and with
      nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase by the modified
      Scherer-Singler's method. RESULTS: On the basis of histological studies using
      rectal biopsies, 20 cases were diagnosed with Hypo, 5 with HD, 2 with intestinal
      neuronal dysplasia (IND), and 82 with normal findings. The incidence of normal
      cases was significantly greater than that of allied disorders of HD including
      both Hypo and IND (P<0.0001). The incidence of Hypo was also significantly
      greater than that of Hypo and IND (P<0.01, P<0.0001, respectively). Both HD and
      IND could be diagnosed by rectal mucosal biopsies with AChE staining. However,
      accurate diagnosis of Hypo could be made only through examination of the
      submucosal and myenteric plexuses by NADPH-diaphorase staining in full-thickness
      rectal specimens. CONCLUSIONS: We were able to obtain accurate diagnosis of
      childhood patients with HD and IND by rectal mucosal biopsy with AChE staining.
      On the other hand, accurate histological diagnosis in patients with Hypo could
      also be obtained by NADPH-diaphorase staining in full-thickness rectal specimens.
      That is to say, it is easier for the investigator to detect the cholinergic fiber
      and ganglion cell in the gut wall using NADPH-diaphorase staining than by using
      AChE staining.

PMID- 15239243
TI  - Restoration of digestive continuity after Hartmann's procedure.
AB  - BACKGROUND/AIMS: Reestablishment of colonic continuity (RDC) following Hartmann's
      procedure is associated with high morbidity (anastomotic leak 4-16%) and
      mortality (0-4%) rates. The aim of this retrospective study is to evaluate the
      morbidity of RDC following Hartmann's procedure, and to analyze the various
      factors which may be able to influence the rate of complications. METHODOLOGY:
      From 1996 to 2002, 74 patients were treated by Hartmann's colectomy. Of these 74
      patients, 40 patients underwent a reestablishment of colonic continuity (54% of
      all the Hartmann's procedures). The common factor of indications is the presence
      of infection in the abdominal cavity, combined with a distended or prepared
      intestine, or both. The mean age was 60 years (33-90). RESULTS: The mean delay
      between Hartmann's operation and the RDC was 139 days (range: 25-450 days) and
      15.5 days (8-57 days) was the mean duration of the hospital stay. The mortality
      rate was 0% and incidence of anastomotic stricture was 2.5%. The morbidity was
      45%. The majority of patients presenting complications had an ASA score of III
      (44.4%), and the patients without complications were for the majority classified
      as ASA I (45.5%) CONCLUSIONS: The RDC is an intervention performed safely after a
      3 to 5-month delay with an acceptable morbidity and a negligible mortality. The
      ASA score is a determining factor for the risk for complications (p<0.05), unlike
      the age. However, patients younger than 50 years benefit from a protective factor
      against complications.

PMID- 15239244
TI  - Efficacy of nutritional therapy for perforating and non-perforating Crohn's
      disease.
AB  - BACKGROUND/AIMS: Enteral nutrition is the currently established primary therapy
      for Crohn's disease in Japan. We examined the effects of postoperative
      nutritional therapy in patients with perforating type and non-perforating type
      Crohn's disease. METHODOLOGY: We retrospectively reviewed the records for 218
      patients who underwent surgical interventions for Crohn's disease in our hospital
      between January 1, 1974 and September 30, 2001. They were divided into four
      groups: 92 patients in the non-perforating type (NP type) + Elemental Diet (ED)
      group had received ED therapy and nutritional education, 22 patients in the NP
      type + NoED group had not received ED therapy or nutritional education, 88
      patients in the perforating type (P type) + ED group and 16 patients in P type +
      NoED group. We evaluated the incidence of reoperation rate for each group.
      RESULTS: Patients with a postoperative ED therapy demonstrated a significant
      decrease in the incidence of second resection. The incidence of second resection
      in the NP type + ED group was significantly lower than that of the other groups.
      The NP type + NoED group and the P type + ED group followed similar courses.
      CONCLUSIONS: In patients with Crohn's disease postoperative ED therapy and
      nutritional education is effective in reducing the incidence of second resection.
      It appears that postoperative ED therapy and nutritional education is more
      important in patients with P type Crohn's disease.

PMID- 15239245
TI  - Role of stapled and hand-sewn anastomoses in recurrence of Crohn's disease.
AB  - BACKGROUND/AIMS: Anastomotic recurrence after bowel resection is a major problem
      in Crohn's disease surgery. The aim of this study is to compare recurrence rate
      after stapled side-to-side ileo-colonic anastomosis to those after stapled end-to
      side or hand-sewn side-to-side anastomosis to distinguish the role of suture
      technique and anastomotic configuration in the prevention of Crohn's disease
      recurrence. METHODOLOGY: Eighty-four consecutive patients who had undergone ileo
      colonic resection for Crohn's disease were enrolled: 12 of them had stapled side
      to-side anastomosis, 36 stapled end-to-side anastomosis and 36 hand-sewn side-to
      side anastomosis. We evaluated duration of operation, first bowel movement after
      operation, postoperative hospital staying, postoperative surgical complications,
      clinical recurrence and reoperation rate. The statistical analysis was performed
      using Student's t-test and Fisher exact test. Cumulative recurrence rates were
      compared using F Cox test and Kaplan-Meier method. RESULTS: No statistically
      significant difference between the three groups was observed in early
      postoperative follow up. The stapled side-to-side anastomosis group obtained a
      better symptom-free survival than the stapled end-to-side group (p=0.04). In the
      stapled and hand-sewn side-to-side groups reoperation rates were significantly
      lower than in the stapled end-to-side group (p=0.01 and p=0.05 respectively).
      CONCLUSIONS: All the three types of anastomosis were demonstrated to be equally
      safe in early postoperative outcome. A longer follow-up showed a significantly
      lower incidence of reoperation recurrence in the stapled and hand-sewn side-to
      side anastomosis compared to the stapled end-to-side anastomosis group. This
      result may suggest the configuration of the anastomosis as the key point in the
      recurrence of anastomotic Crohn's disease.

PMID- 15239246
TI  - Laparoscopic adhesiolysis for recurrent postoperative small bowel obstruction.
AB  - BACKGROUND/AIMS: Recurrent small bowel obstruction caused by postoperative
      adhesions has been treated by conventional laparotomy, however laparoscopic
      management of acute and recurrent small bowel obstruction has been demonstrated.
      This study assessed the clinical outcome and long-term efficacy of laparoscopic
      adhesiolysis for recurrent adhesive small bowel obstruction. METHODOLOGY:
      Elective laparoscopic treatment following conservative management was attempted
      in 25 patients hospitalized for recurrent small bowel obstruction after abdominal
      or pelvic surgery. RESULTS: The pathologic sites of postoperative adhesions and
      adhesive types were identified laparoscopically in all patients. Complete
      laparoscopic adhesiolysis was feasible in 18 patients (72%), while conversion to
      laparoscopic-assisted adhesiolysis (mini-laparotomy with an incision less than 4
      cm long) was required in 6 patients (24%) because of dense adhesion or the
      technical difficulties due to adhesion in the pelvic cavity. Conversion to
      laparotomy was required for one patient because of excessive adhesions and
      intestinal perforation (4%). Long-term follow-up was possible in all patients.
      There was no recurrence of small bowel obstruction over a mean follow-up period
      of 41 months. CONCLUSIONS: Laparoscopic adhesiolysis is a safe and effective
      treatment for recurrent small bowel obstruction in selected cases. Conversion to
      mini-laparotomy or laparotomy should be considered in patients with dense or
      pelvic adhesion.

PMID- 15239247
TI  - The safety and feasibility of percutaneous endoscopic gastrostomy placement.
AB  - BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy (PEG) is now becoming
      increasingly popular. However, an increasing number of complications has also
      been reported. Regarding such complications, iatrogenic perforation of the colon
      is considered to be the most dangerous. METHODOLOGY: We routinely check the
      course of the colon using preoperative abdominal computed tomography with air
      injected into the stomach (pre-PEG CT), and thereafter the patients are
      classified into two groups, consisting of a Low-risk group and High-risk group,
      according to the locations of the stomach and colon. The patients in the High
      risk group underwent PEG in combination with contrast radiography of the large
      intestine. We evaluated the safety and feasibility of PEG placement using a Pre
      PEG CT and contrast radiography of the large intestine. RESULTS: A Pre-PEG CT
      showed a Low-risk type in 84.4% and a High-risk type in 15.6%. High-risk type
      patients underwent contrast radiography on the large intestine in conjunction
      with PEG. As a result, we were able to perform PEG safely with no iatrogenic
      perforation in any patients. CONCLUSIONS: A pre-PEG CT and contrast radiography
      of the large intestine combination with PEG are thus considered to be an
      effective modality for reducing the incidence of serious complications of PEG.

PMID- 15239248
TI  - Arteriovenous malformation of the jejunum detected by arterial-phase enhanced
      helical CT, a case report.
AB  - This is a report on a case of arteriovenous malformation of the jejunum, which is
      a relatively rare occurrence that can be detected by helical computed tomography
      (helical CT). The patient was a 63-year-old man who was admitted to our hospital
      because of a tarry stool. He developed hypotension as a result of losing a large
      amount of bright-red blood through rectal bleeding and was given fluids and blood
      transfusions. Subsequently, a helical CT scan was performed at 10-mm slice
      thickness. A small high-density area in the jejunum was identified on the
      arterial phase, which was scanned 30 sec after an intravenous infusion of 100 mL
      of iopamidol at a rate 2.5 mL/sec. An emergency operation, based on the diagnosis
      of bleeding from the jejunum, was performed because the patient had developed
      hypotension once again. A small, elevated lesion, which coincided with the high
      density area detected by helical CT, was found in the jejunum. A segmental
      resection and end-to-end anastomosis were done. The pathological diagnosis
      revealed an arteriovenous malformation of the jejunum. In conclusion, helical CT
      may be an effective noninvasive method for detecting the cause and site of
      gastrointestinal bleeding.

PMID- 15239249
TI  - Recurrent hemorrhagic shock from solitary jejunal diverticulum.
AB  - We report the case of recurrent hemorrhagic shock manifested by massive melena
      and hematemesis in a 67-year-old patient, previously operated in another hospital
      for an abdominal aortic aneurysm two weeks before. During hospitalization the red
      blood cell scintigraphy was positive for bleeding in the jejunum. Intraoperative
      endoscopy was performed to identify a solitary diverticulum at the proximal
      jejunum. Approximately 70 cm of the involved segment was resected by an end-to
      end anastomosis. Postoperative one-year evolution has been favorable, without any
      evidence of rebleeding. A review of the literature concerning this disease
      indicates the rarity of a massive bleeding from solitary jejunal diverticulum and
      the need to consider this condition in patients with gastrointestinal hemorrhage.

PMID- 15239250
TI  - Chemotherapy and serum hyaluronic acid levels in malignant peritoneal
      mesothelioma.
AB  - We report a case of malignant peritoneal mesothelioma in a 63-year-old man. Right
      hemicolectomy, partial ileectomy, partial omentectomy, excision of the abdominal
      wall, and catheterization for intraperitoneal infusion chemotherapy were
      performed as surgery. Histopathologically, the tumor was composed of papillary
      and sheet-like proliferation of atypical cells for which an Alcian Blue digestive
      test with hyaluronidase was positive. By immunohistochemical staining, the tumor
      cells were stained against HBME-1 and thrombomodulin antibodies. The final
      diagnosis was a diffuse malignant mesothelioma of the epithelial type. Sequential
      adjuvant chemotherapies of cisplatin (ip) plus 5-fluorouracil (iv), cisplatin
      (iv) plus 5-fluorouracil (iv), and mitomycin C (iv) were administered. He is
      still alive 46 months after surgery. Moreover, the increase in serum hyaluronic
      acid levels has been related to tumor volume, and has been useful for clinical
      follow-up. Secondly, we reviewed major chemotherapy previously described for
      malignant mesothelioma. The total response rate was 469 of 2,493 cases (18.8%).
      The response rates with single agent chemotherapy, combination chemotherapy,
      intraperitoneal or intracavitary chemotherapy, continuous hyperthermic peritoneal
      perfusion chemotherapy, and immunochemotherapy were 150 of 1,146 cases (13.1%),
      209 of 1,019 cases (20.5%), 63 of 133 cases (47.4%), 11 of 13 cases (84.6%), and
      36 of 182 cases (19.8%), respectively. Direct exposure of antitumor agent to the
      peritoneal surface is considered to be most effective against malignant
      peritoneal mesothelioma.

PMID- 15239251
TI  - Limitation of portal vein embolization for extension of hepatectomy indication in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Although percutaneous trans-hepatic portal vein embolization
      (PTPE) expands the candidate pool for hepatectomy in patients with hepatobiliary
      malignancies, the role of PTPE in patients with active hepatitis or cirrhosis has
      yet to be determined. METHODOLOGY: Records of patients who underwent PTPE of the
      right portal vein between 1984 and April 2001 were reviewed retrospectively. To
      determine the indication for PTPE and subsequent hepatectomy, clinical variables,
      including serum concentrations of hyaluronic acid (HA), procollagen type III
      peptide (P-III-P), and the 7S domain of type IV collagen (7S-IV), were compared
      between patients who underwent right hepatectomy (group A; n=44) and the other
      patients (group B; n=17). RESULTS: The scores for prediction of postoperative
      liver failure (prediction score) and serum HA and P-III-P concentrations were
      different in the two groups. Thirteen of 30 patients (43%) whose prediction score
      was more than 50, the limit of the hepatectomy without PTPE, successfully
      underwent right hepatectomy following PTPE. The resectability ratios increased to
      75% and 100%, when the HA concentration was < or = 100mg/L and the P-III-P
      concentration < or = 0.7/mL. CONCLUSIONS: Serum HA and P-III-P concentrations are
      useful guidelines for identifying candidates for right hepatectomy following
      PTPE.

PMID- 15239252
TI  - Immunological response in chronic hepatitis C virus infection during interferon
      alpha therapy.
AB  - BACKGROUND/AIMS: Chronic hepatitis C infection is a serious therapeutic problem.
      Interferon therapy is one of the possible methods leading to HCV infection
      elimination in some patients. The aim of the study was the estimation of
      administration of interferon alpha 2a and its effect on the lymphocyte
      subpopulations in peripheral blood in patients with chronic hepatitis C.
      METHODOLOGY: A cytometric analysis was completed concerning the level of CD19+,
      CD3+, CD4+, CD8+, CD4+ + HLA DR+, CD16+ + 56+ in 21 patients in the 0, 4, 24, 48
      weeks of interferon alpha 2a treatment, with the dose of 18 MU/week/48 weeks.
      RESULTS: Virus elimination was obtained in 26% of patients (responders, R) and a
      higher CD8+ level and a decrease in CD4+ was observed during interferon
      administration in those patients. A slight increased NK cell level was noticed
      mainly in patients who did not eliminate HCV (non-responders, NR). In R patients,
      lower lymphocyte values of CD19+, NK, CD3+ + HLA DR+, and CD4+ were observed in
      comparison to NR, which could suggest that they play a role in the process of HCV
      elimination. Significant immunological changes in peripheral blood were observed
      mainly in the first 4 weeks of interferon alpha therapy. CONCLUSIONS: Our studies
      did not reveal whether any of examined lymphocyte subpopulations in peripheral
      blood could be considered as a predictive factor of a positive reaction to
      interferon alpha treatment. However, there are significant differences in the
      levels of lymphocytes in R and NR.

PMID- 15239253
TI  - 101 hepatectomies under continuous inflow occlusion following simple in-situ
      liver cooling in patients with chronic liver diseases.
AB  - BACKGROUND/AIMS: Hepatic inflow occlusion involves the serious disadvantage of
      ischemic injury to the remnant liver, particularly in patients with injured
      parenchyma. Liver hypothermia is one of the solutions for this problem. The
      purpose of this study was to evaluate simple in-situ liver cooling method of
      performing hepatic resection under continuous inflow occlusion in patients with
      chronic liver disease. METHODOLOGY: One hundred and one patients with chronic
      hepatitis (n = 26) and cirrhosis (n = 75) were included in this retrospective
      study. They underwent hepatectomy under conditions of continuous inflow occlusion
      immediately following simple in-situ liver cooling. Laboratory data and
      intraoperative and postoperative variables were analyzed for the three groups of
      patients stratified according to the lowest liver tissue temperature achieved:
      group 1 (> or = 30 degrees C, n = 16), group 2 (< 30 degrees C and > or = 25
      degrees C, n = 62) and group 3 (< 25 degrees C, n = 20). RESULTS: Our simple in
      situ liver cooling method enabled us to safely resect chronically diseased liver
      under continuous inflow occlusion (49.8 +/- 7.7 min, mean +/- SD; range, 30 to 70
      min) with acceptable operative blood loss (894 +/- 853mL), morbidity (22.7%,
      23/101) and mortality (1.0%, 1/101); one patient died of complications unrelated
      to ischemic injury. Analysis demonstrated that simple liver hypothermia was
      substantially hepatoprotective against ischemic injury in terms of serum
      transaminase levels and duration of inflow occlusion, particularly when the liver
      tissue temperature fell below 30 degrees C (groups 2 and 3). CONCLUSIONS: Hepatic
      inflow occlusion can be safely employed in a continuous manner for approximately
      1 hour, even during resection of chronically diseased liver, particularly when
      the liver is cooled below 30 degrees C prior to hepatic clamping by our simple in
      situ hypothermia technique.

PMID- 15239254
TI  - Treatment of HCC with pravastatin, octreotide, or gemcitabine--a critical
      evaluation.
AB  - BACKGROUND/AIMS: New perspectives in the treatment of advanced hepatocellular
      carcinomas have recently been inaugurated with the application of
      hydroxymethylglutaryl coenzyme A reductase inhibitors i.e. pravastatin, the
      somatostatin analogue octreotide, or the cytidine analogue gemcitabine. The
      present study aimed to evaluate these substances in patients with progressive
      tumor growth. METHODOLOGY: A total of 58 patients either received 3 x 200
      microg/day octreotide for 2 months followed by 20mg octreotide LAR every 4 weeks
      (n=30) or 40-80 mg pravastatin (n=20) or 80-90 mg/m2 gemcitabine over 24 hours
      weekly in cycles of 4 weeks (n=8). Kaplan-Meier survival curves and the log-rank
      test were used for univariate comparison of sur vival. RESULTS: The median
      overall survival of patients receiving octreotide was 5 months, of patients
      receiving pravastatin 7.2 months and of patients receiving gemcitabine 3.5
      months. The difference between the pravastatin and the gemcitabine groups was
      significant. No WHO grade 3 or 4 side effects were seen in either group of
      patients. CONCLUSIONS: These results do not confirm those of former studies.
      Neither pravastatin, nor octreotide, nor gemcitabine did prolong the patients'
      median overall survival as compared to control groups reported by other authors.
      New therapeutic strategies have to be found for patients with advanced
      hepatocellular carcinomas.

PMID- 15239255
TI  - Diagnostic and prognostic value of virologic tests in vertical transmission of
      hepatitis C virus infection: results of a large prospective study in pregnant
      women.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the value of virologic tests for
      the diagnosis and prognosis of hepatitis C virus (HCV) vertical transmission in a
      large cohort of human immunodeficiency virus (HIV)-seronegative pregnant women.
      METHODOLOGY: HCV RNA and viral load were tested at the first and third trimester
      of pregnancy as well as at time of delivery, and from their newborns at birth and
      after 6, 12, 24, and 36 months. Viral genotype was determined in both viremic
      mothers and newborns. RESULTS: Antibodies to HCV were detected in 119 mothers
      (0.57%), whereas serum HCV RNA tested positive in 67% of them. Interestingly,
      presence of serum HCV RNA was only observed in 2 babies born to 80 HCV RNA
      positive mothers (transmission rate: 2.4%), appearing immediately after birth and
      remaining positive during the entire follow-up (36 months). These two babies
      raised serum transaminase levels and had the same HCV genotype (1b) as their
      respective mothers who had intermediate or low viral load. CONCLUSIONS: Vertical
      HCV transmission is an infrequent event among HIV-negative HCV-infected mothers,
      and the presence of serum HCV RNA immediately after birth had a high diagnostic
      and prognostic value, as identified those newborns who developed chronic
      hepatitis C.

PMID- 15239256
TI  - Additive therapeutic effects of the liver extract preparation mixture adelavin-9
      on interferon-beta treatment for chronic hepatitis C.
AB  - BACKGROUND/AIMS: We previously reported that intravenous interferon-beta
      administration was effective in treating patients with chronic hepatitis C and
      that there was no significant correlation between the response to therapy and
      host in vitro immunoglobulin production. The aims of this study were to evaluate
      the additive effect of a liver extract preparation and flavin adenine
      dinucleotide mixture and to reevaluate the correlation. METHODOLOGY: 65 patients
      with chronic hepatitis C received intravenously 6 million units of interferon
      beta and 2 mL of a liver extract preparation and flavin adenine dinucleotide
      mixture. The results of this study were compared with those of our previous
      study, on interferon-beta monotherapy in 91 patients with chronic hepatitis C. In
      addition, peripheral blood mononuclear cells were obtained before interferon-beta
      administration and cultured. Immunoglobulin concentrations in their supernatants
      were measured and the correlation with the interferon response was evaluated.
      RESULTS: The virological end-of-treatment or sustained response occurred in 49 of
      58 cases (84.5%), and 16 of 58 cases (27.6%), respectively. Biochemical end-of
      treatment or sustained responses occurred in 22 of 58 cases (37.9%), and 30 of 58
      cases (51.7%), respectively. These response rates were higher than those reported
      in our previous study of interferon monotherapy. Monovariate analysis indicated
      that the use of the liver extract preparation and flavin adenine dinucleotide
      mixture was a significant predictor of the virological end-of-treatment response
      and the sustained biochemical response, but by multivariate analysis these
      relationships were not significant. Immunoglobulin production was not correlated
      with the virological and biochemical responses. CONCLUSIONS: This study indicated
      that combination therapy with intravenous interferon-beta and the liver extract
      preparation and flavin adenine dinucleotide mixture was more effective than
      intravenous interferon-beta monotherapy. However, no correlation between the
      interferon response and in vitro immunoglobulin production was observed.

PMID- 15239257
TI  - Survival after gamma interferon intratumoral injections in a model of
      hepatocarcinoma.
AB  - BACKGROUND/AIMS: Short-term efficacy of local gamma interferon delivered via a
      single injection of an adenovirus-gamma interferon vector has been reported in
      immunocompetent animals which develop spontaneous liver cancer. However the long
      term outcome was not examined. The aim of this randomized trial was to assess in
      an immunodeficient mouse ectopic model the benefit, if any, of the long-term
      efficacy of intratumoral injections of gamma interferon itself. METHODOLOGY: 77
      mice were randomly assigned to 4 groups. Gamma interferon treated groups received
      a dose of 5000, 10000 or 20000 IU per animal versus phosphate-buffered saline.
      The follow-up lasted 46 days. RESULTS: Significant differences were noted in mice
      receiving 20000 IU compared to controls: increase in survival (p=0.0485), slowing
      down of tumor growth in large tumors (p=0.009), increase in necrosis (p=0.004).
      The preferential staining in necrotic areas with anti-Class II antibody and the
      accumulation of nuclear debris indicated that neutrophils were involved.
      CONCLUSIONS: Gamma interferon could accentuate the migration of non-specific
      immune cells to necrotic areas which occur spontaneously in large tumors. These
      results in animals bearing large tumor suggest that it may be worthwhile to
      explore local gamma interferon delivery to patients with extensive
      hepatocarcinoma.

PMID- 15239258
TI  - CD44 and VEGF expression in extrahepatic metastasis of human hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: We investigated the correlation between vascular endothelial
      growth factor (VEGF) and CD44 expression in hepatocellular carcinoma (HCC) and
      the frequency of extrahepatic metastasis, in order to evaluate the influence of
      vascular growth and adhesion molecules in facilitation of distant metastasis.
      METHODOLOGY: We obtained materials from primary lesions of HCC with no
      extrahepatic metastasis (control group) and primary lesions and metastatic
      lesions with extrahepatic metastasis (metastasis group). Immunohistochemical
      staining was performed using anti-human CD44v3 monoclonal antibodies and anti
      human VEGF ab-3 monoclonal antibodies. Although pathological parameters such as
      tumor size, differentiation, capsule formation, and vascular invasion were
      analyzed, there was no marked difference among the groups. RESULTS: Percentages
      of nodules with VEGF-positive tumor and sinusoidal cells were low in primary
      lesions of the control and metastasis groups, while high in metastatic lesions in
      the metastasis group. On the other hand, percentages of nodules with CD44
      positive tumor and sinusoidal cells were low in primary lesions of the control
      group, while high in primary lesions and metastatic lesions of the metastasis
      group. CONCLUSIONS: The present study demonstrated that CD44 expression in
      primary lesions is related to a higher frequency of extrahepatic metastasis,
      suggesting that this is a clinicopathologically useful parameter in predicting
      the occurrence of distant metastasis.

PMID- 15239259
TI  - Reticulated platelets as a marker of megakaryopoiesis in liver cirrhosis;
      relation to thrombopoietin and hepatocyte growth factor serum concentration.
AB  - BACKGROUND/AIMS: Thrombocytopenia often accompanies chronic liver diseases. It
      can occur due to the decrease in blood platelet production by megakaryocytes, the
      increase in peripheral destruction, or splenic sequestration. METHODOLOGY: We
      estimate the reticulated platelets by use of flow cytometry in patients with
      liver cirrhosis with thrombocytopenia (n-24, platelets median (M)-77g/L), with
      normal platelet count (n-16, platelets M-193g/L) and in healthy (n-27, platelets
      M-242g/L). The level of reticulated platelets was determined in whole peripheral
      blood stained with thiazole orange and incubated with monoclonal antibodies anti
      CD41. RESULTS: Patients with liver cirrhosis and thrombocytopenia revealed
      significantly lower reticulated platelet levels than patients without
      thrombocytopenia and healthy subjects (M-1.0% vs. 1.5% vs. 2.0% respectively).
      The correlation between reticulated platelet level and platelet count, serum
      level of thrombopoietin and hepatocyte growth factor in liver cirrhosis was not
      established. An inverse correlation was noted between reticulated platelets and
      thrombopoietin (r - 0.6, p<0.01) and hepatocyte growth factor (r - 0.5, p<0.01)
      in the control group. A positive correlation between platelet count in liver
      cirrhosis and serum level of thrombopoietin (r - 0.35, p<0.05) and hepatocyte
      growth factor (r - 0.48, p<0.01) was observed. CONCLUSIONS: Our studies showed
      that decreased production of platelets by megakaryocytes due to low
      thrombopoietin concentration could be a possible cause of thrombocytopenia in
      liver cirrhosis.

PMID- 15239260
TI  - Ultrasound-guided percutaneous boiling carboplatin injection (PBCI) for the
      treatment of small hepatocellular carcinoma: a preliminary study.
AB  - BACKGROUND/AIMS: To evaluate the therapeutic efficacy of ultrasound-guided
      percutaneous injection of boiling carboplatin (PBCI) for small hepatocellular
      carcinoma (HCC). METHODOLOGY: PBCI was used to treat 34 HCC patients with 57
      tumor nodules less than 3cm in diameter. Thirty-two of them (94.1%) were
      recurrent cases, including postoperative recurrence in 28, recurrence after
      percutaneous microwave coagulation therapy in 2 and recurrence after
      transcatheter arterial chemoembolization in 2. The remaining 2 had an initially
      treated HCC. Two sessions of PBCI were administered within 1 week for each tumor
      nodule. Its influences on liver function and blood cell count were monitored.
      Local recurrence rate, incidence of distant recurrence and survival rate were
      calculated by Kaplan-Meier method and their influencing factors were analyzed.
      RESULTS: Patients had a mean follow-up time of 12.7 +/- 5.4 months (from 3 to 22
      months). Amount of boiling carboplatin solution (5mg/mL) injected per session
      ranged from 3mL to 35mL (10.9 +/- 6.9mL), and the total amount used in the two
      session course ranged from 6mL to 65mL (21.8 +/- 13.4mL). Of 57 tumor nodules
      treated with two-session PBCI, technical success was achieved in 53 (93.0%). The
      cumulative local recurrence rate at 3, 6, 12, 18 months was 3.5%, 7.3%, 16.2% and
      16.2%, respectively, with a mean local recurrence-free time of 19.4 +/- 0.8
      months. Eighteen out of 34 patients (52.9%) developed distant recurrence, with a
      mean interval time to distant recurrence of 11.6 +/- 1.4 months. Incidence of
      distant recurrence at 6, 12, 18 months was 34.1%, 53.2% and 64.5%, respectively.
      The 1-year and 1.5-year survival rates were 78.3% and 64.2%, respectively, with a
      mean survival time of 17.8 +/- 1.1 months. Of 28 postoperative recurrent
      patients, PBCI markedly prolonged the mean postoperative tumor-free survival time
      from 21.1 +/- 3.4 months to 36.2 +/- 4.7 months (p<0.01). Univariate analysis
      demonstrated that patients with Child-Pugh grade A liver function had a
      significantly longer survival time and greater survival rate than those with
      grade B and C (p<0.05). There were no remarkable changes in liver function and
      complete blood cell count after PBCI and no major complications were observed.
      CONCLUSIONS: PBCI represented as an effective and safe percutaneous injection
      therapy for small HCC. It needed only two sessions for the vast majority of HCC
      less than 3cm in diameter and thus had the advantage of being much less invasive.

PMID- 15239261
TI  - A comparative randomized trial of intermittent intrahepatic arterial carboplatin-
      versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage
      IV).
AB  - BACKGROUND/AIMS: The study was performed to investigate the anti-tumor effect,
      survival rate, and toxicity of intermittent intrahepatic infusion chemotherapy
      with carboplatin suspended in lipiodol. METHODOLOGY: We conducted a randomized
      controlled study containing either doxorubicin or carboplatin in 65 patients with
      advanced hepatocellular carcinoma. RESULTS: The results observed in the
      carboplatin- and doxorubicin-lipiodol groups included: response rates, 29.0 and
      20.6% respectively, 1-year survival rates of, 60.4% and 40.4%, respectively, and
      the difference achieved statistical significance (p=0.025). The median survival
      of 31 patients who received carboplatin emulsified with lipiodol was 16.9 months,
      34 patients who received doxorubicin was 12.1 months. The difference achieved
      statistical significance. CONCLUSIONS: Compared with doxorubicin, carboplatin
      caused neither cardiotoxicity nor nephrotoxicity, and side effects of nausea and
      vomiting were less severe. Therefore, carboplatin is effective and preferable for
      repeated intrahepatic arterial administration to treat advanced hepatocellular
      carcinoma over a relatively long period.

PMID- 15239262
TI  - A clinicopathological study of inflammatory pseudotumors of the liver with
      special reference to vessels.
AB  - BACKGROUND/AIMS: Inflammatory pseudotumor of the liver is rare, and patients with
      inflammatory pseudotumor frequently undergo unnecessary surgical resection as a
      result of misdiagnosis of malignancy. In this study, we therefore investigated
      inflammatory pseudotumor clinicopathologically to clarify its characteristics.
      METHODOLOGY: Twenty patients including 3 with inflammatory pseudotumor and 17
      with various malignant liver tumors were studied. We further investigated tumor
      vessels by means of immunohistochemistry using monoclonal antibodies against
      CD34, factor VIII-related antigen and alpha-smooth muscle actin. RESULTS:
      Although serum levels of alkaline phosphatase were significantly higher in
      inflammatory pseudotumor patients than in other patients, the laboratory data
      alone could not precisely distinguish inflammatory pseudotumor from other hepatic
      tumors. On imaging studies such as ultrasonography and computed tomography,
      significant changes in tumor size, especially size reduction, during relatively
      short follow-up periods were often observed in inflammatory pseudotumor but not
      in other liver tumors. An enhancement of the peripheral regions of inflammatory
      pseudotumor was frequently observed in the early phase of contrast-medium dynamic
      computed tomography. This might be due to abnormal vessels located in the
      peripheral regions of inflammatory pseudotumor which might result from
      obliteration of some pre-existing vessels in portal tracts within inflammatory
      pseudotumor. Immunohistochemical analysis further revealed that abnormal vessels
      in the peripheral regions of inflammatory pseudotumor were positively stained
      with CD34, factor VIII-related antigen and alpha-smooth muscle actin as were
      tumor sinusoids within hepatocellular carcinoma and tumor capillaries in other
      malignant liver tumors. CONCLUSIONS: Although inflammatory pseudotumor seems to
      have some features in imaging studies, a biopsy is needed for a correct diagnosis
      of inflammatory pseudotumor.

PMID- 15239263
TI  - A resected case of metachronous liver metastasis from lung cancer producing alpha
      fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II
      (PIVKA-II).
AB  - A resected case of huge liver metastasis of hepatoid adenocarcinoma of the lung
      is described. A 77-year-old man who presented a solitary huge liver tumor was
      admitted to our hospital. He had undergone right lower lobectomy of the lung for
      lung cancer one year before. The view of imaging studies was not a typical one of
      hepatocellular carcinoma. Serum levels of AFP and PIVKA-II were 334,500ng/mL and
      3,890mAU/mL, respectively, and the proportion of AFP L3 was 97.9%. It was thought
      that they were strongly diagnostic for hepatocellular carcinoma. Extended right
      lobectomy of the liver was performed. Microscopically, it was poorly
      differentiated adenocarcinoma and diagnosed as liver metastasis from the formerly
      resected lung cancer. The tumor was composed of cells with both sheet-like growth
      and tubule formation. The neoplastic cells, in the sheet-like growth resembled
      hepatocellular carcinoma cells. By immunohistochemical staining with anti-AFP and
      anti-PIVKA-II antibodies, cancer cells of both the primary and metastatic lesions
      were positive. The patient eventually died of multiple liver and bone metastasis
      6 months after the operation.

PMID- 15239264
TI  - Microwave coagulation therapy for a liver tumor involving the root of the left
      hepatic vein of the residual liver after extended right hepatectomy.
AB  - A 54-year-old man had received low anterior resection for rectal carcinoma and
      extended right hepatectomy for a metastatic liver tumor. One year later, imaging
      studies disclosed a metastatic liver tumor in segment 2 of the liver. The
      residual left hepatic vein was completely invaded by the tumor from the root of
      the hepatic vein to the confluence of several branches by intraoperative
      ultrasonography. To resect partial liver with the involved hepatic vein was
      deemed impossible. Microwave coagulation therapy was performed on the tumor and
      the involved hepatic vein, as we had established the safety of microwave
      irradiation to the main hepatic vein without interference of the hepatic venous
      flow in an experimental study. The patient remains well 40 months after the
      surgery without recurrent signs. The hepatic venous flow of the irradiated
      hepatic vein is maintained well according to serial examination of Doppler
      ultrasonography.

PMID- 15239265
TI  - Rapid growth of liver hemangioma following interferon treatment for hepatitis C
      in a young woman.
AB  - Liver hemangioma is the most common benign liver tumor. Giant hemangiomas can
      grow and give various clinical symptoms. We describe a case of rapid growth of
      liver hemangioma in a seventeen-year-old girl. She was treated with interferon
      alpha 2b for hepatitis C. About 12 months later she was admitted to the hospital
      with symptoms of large epigastric mass, anemia and thrombocytopenia. Ultrasound
      scan and computed tomography confirmed the clinical picture, suggesting giant
      liver hemangioma. During surgery large cavernous hemangioma deeply penetrating
      into normal liver parenchyma was found. In view of recent hepatitis C infection
      the resection procedure (left extended hemihepatectomy) was assessed as being
      dangerous for the patient's life. Ligation of the left branches of hepatic artery
      and portal vein reducing tumor blood supply was performed. The postoperative
      period was uneventful; the hemangioma in the left lobe had shrunk. Ultrasound and
      CT scans performed one and two years after surgery showed that the size of the
      hemangioma remained stable and the patient was asymptomatic. In this described
      case three potential factors stimulating the growth of hemangioma (puberty,
      hepatitis C infection and interferon treatment) are discussed. The potential role
      of vascular endothelial growth factor and fibroblast growth factor is raised.

PMID- 15239266
TI  - Surgical treatment for an extrahepatic portosystemic shunt: a case report.
AB  - An extrahepatic portosystemic shunt that has neither liver cirrhosis nor portal
      hypertension is rare. A 60-year-old Japanese woman who had been suffering chronic
      liver disease and anemia with mild disorientation was admitted to investigate
      general fatigue with dizziness and disorientation. The laboratory data revealed
      mild pancytopenia and liver dysfunction including hyperammoniemia, an increased
      Indocyanine Green 15-min retention rate, and a decreased Fischer's ratio. Color
      Doppler ultrasonography, computed tomography, and arterial portography revealed
      an extrahepatic portosystemic shunt that extended tortuously from the superior
      mesenteric vein into the inferior vena cava, and decreased blood flow in the main
      portal vein. Judging from intraoperative measurement of portal pressure and
      intraoperative portography, shunt ligations were performed at both the efferent
      portion of shunt from the superior mesenteric vein and the afferent portion of
      the shunt into the inferior vena cava, and resection of the spleen was also
      performed. On the postoperative laboratory data, pancytopenia disappeared, and
      liver function improved. Postoperative abdominal imaging showed increased blood
      flow in the main portal vein and disappearance of the shunt vessel. Moreover,
      symptoms present before surgery also disappeared. In conclusion, surgical
      treatment of extrahepatic portosystemic shunts may result in better postoperative
      quality of life if it is performed in carefully selected patients.

PMID- 15239268
TI  - Portal vein aneurysm: report of two cases.
AB  - Portal vein aneurysm is a rare entity. We present two cases of extrahepatic
      portal vein aneurysms, which were incidentally discovered in patients with no
      evidence of liver disease. Those were assumed to be congenital lesions. Diagnosis
      was made by Doppler ultrasound. Both patients were managed expectantly.

PMID- 15239267
TI  - Metastasis of hepatocellular carcinoma to the supramaxillary gingiva and right
      ventricle.
AB  - We describe a rare double metastasis of hepatocellular carcinoma to the
      supramaxillary gingiva and papillary muscle of the right ventricle. The patient
      was a 72-year-old woman who underwent three sessions of transcatheter arterial
      embolization for the primary lesions. Control of bleeding from the supramaxillary
      gingival metastasis was difficult by conservative treatment such as compression
      with gauze soaked in epinephrine. Therefore, radiotherapy was performed, but it
      failed to control the bleeding. The patient subsequently died due to hepatic
      failure. Autopsy revealed metastases of hepatocellular carcinoma to the papillary
      muscle of the right ventricle and paraaortic lymph node in the abdomen in
      addition to the supramaxillary gingival metastasis. Histopathological examination
      showed moderately differentiated hepatocellular carcinoma of both the primary
      site and metastatic sites to the gingiva and the heart and poorly differentiated
      in the paraaortic lymph node.

PMID- 15239269
TI  - Is fenestration a safe treatment for adult polycystic liver disease?: A report of
      refractory complications.
AB  - We report a 67-year-old man with highly symptomatic polycystic liver disease.
      Fenestration was selected to treat symptoms because the cysts were scattered
      diffusely and the normal liver volume was limited. Although this patient was
      relieved from symptoms of liver cysts consequently, several severe postoperative
      complications including disseminated intravascular coagulation, respiratory
      failure, liver failure, and biliary leakage occurred resulting in a 6-month
      postoperative hospital stay. Although various treatments for symptomatic adult
      polycystic liver disease have been advocated, a definitive treatment remains
      controversial, especially in diffuse adult polycystic liver disease. Fenestration
      is one of the alternative treatments for the patients whose cysts are difficult
      to resect. However high morbidity rate should be carefully assessed, if extensive
      fenestration is needed to treat diffuse adult polycystic liver disease. Further
      consideration of appropriate treatments for diffuse adult polycystic liver
      disease is needed.

PMID- 15239270
TI  - Transjugular intrahepatic portosystemic shunt in cavernomatous portal vein
      occlusion.
AB  - A 72-year-old patient with liver cirrhosis and cavernomatous portal vein
      occlusion presented with refractory ascites. We treated the patient with
      transjugular intrahepatic portosystemic shunt: transjugular transhepatic puncture
      of an intrahepatic hilar collateral vein was performed; transjugular intrahepatic
      portosystemic shunt was created between the right hepatic vein and the patent
      superior mesenteric vein using this hilar collateral vein as the connecting
      pathway. The ascites was resolved and the patient remains asymptomatic, while
      shunt patency is maintained 16 months after the intervention.

PMID- 15239271
TI  - Quality of life following acute necrotizing pancreatitis.
AB  - BACKGROUND/AIMS: The authors examine the quality of life of patients treated for
      acute necrotizing pancreatitis an average of 37.8 months following their illness.
      METHODOLOGY: The questionnaire used in the examinations was a version of the
      Short Form-36 (SF-36) which was adapted to a Hungarian environment and included
      additional questions regarding the patient's illness. During the treatment of the
      pancreatic necrosis, prophylactic antibiotic treatment, early nasojejunal
      feeding, percutaneous peripancreatic drainage, and late surgical necrectomy was
      used. Postoperatively the lavage of the closed omental bursa was performed.
      RESULTS: It was determined that 77.3% of patients considered their quality of
      life to be good or fair. Quality of life was considered worse in older patients,
      patients with complaints of abdominal distension and bowel problems, patients who
      had lost significant amounts of weight since their illness, patients with poor
      appetite, and patients who were female. CONCLUSIONS: The long-term result, and
      the quality of life after acute necrotizing pancreatitis is good.

PMID- 15239272
TI  - Hepatic arterial infusion of 5-fluorouracil and extrabeam radiotherapy for liver
      metastases from pancreatic carcinoma.
AB  - BACKGROUND/AIMS: To examine the efficacy and safety of a combined modality
      therapy consisting of hepatic arterial infusion of 5-fluorouracil and external
      beam radiotherapy in patients with advanced pancreatic carcinoma. METHODOLOGY:
      Hepatic arterial infusion chemotherapy consisted of 5-FU 1000mg/m2 administrated
      as a 5-hr continuous infusion once weekly. External-beam radiotherapy (total
      dose, 50Gy; 2Gy/day) was delivered to the pancreas tumor concurrently for 5-6
      weeks. Seventeen patients with no distant metastases except to the liver were
      enrolled in this study. RESULTS: Patients received a median of 13 cycles of
      chemotherapy. Sixteen of 17 patients received a total radiotherapy dose of 50Gy.
      In one patient, treatment was discontinued after 24Gy of radiotherapy and 2
      cycles of chemotherapy because of progressive disease. Nausea and vomiting were
      the most common types of toxicity. Grade 3 or worse toxicity was observed in 2
      patients. Four patients developed gastroduodenal ulcers. Of the 16 patients, 7
      (41%) showed a partial response, and 9 (53%) showed no change. The median overall
      survival was 4.5 months and 1-yr overall survival of 11.8% was observed.
      CONCLUSIONS: The combined therapy is active and well tolerated, but results in a
      poorer prognosis, in spite of its high initial response rate.

PMID- 15239273
TI  - Long-term follow-up results of surgery for chronic pancreatitis.
AB  - BACKGROUND/AIMS: Based on a mean follow-up period of 86 months, the long-term
      results of 87 drainage and resection operations performed for chronic
      pancreatitis between 1990-94 were evaluated. METHODOLOGY: To evaluate the
      results, two questionnaires were filled out by the patients. The first was
      related to the pancreatitis and the long-term complications, the second was a
      Gastrointestinal Quality of Life Index questionnaire. Data of deceased patients
      were collected with the help of general practitioners. RESULTS: Based on the
      analysis of disease-related and quality of life questionnaire forms only 34% of
      the investigated patients could be classified as a group showing good results.
      There was a high incidence of long-term mortality (25%). Eighty-three percent of
      the deceased patients (18 patients) died after the seventh postoperative year.
      The most threatened group seems to be the alcoholic and insulin-dependent
      diabetic one. The combination of the two pathologies was the cause of death in a
      third of the cases. Insulin-dependent diabetes mellitus developed in 13 patients
      after an average of 3.9 years following surgery, mainly as a consequence of the
      irreversible and progressive nature of disease. The rate of disability was 51%.
      No significant difference could be demonstrated between the resected and the
      decompressed group according to either disability or late mortality rate.
      CONCLUSIONS: Based on these results, the authors wish to emphasize that in
      chronic pancreatitis the short-term follow-up results may be deceptive, and that
      the real outcome of the surgical treatment can only be expected five years
      following surgery.

PMID- 15239274
TI  - Safety of portal vein resection using centrifugal pump-assisted venous bypass
      between the superior mesenteric vein and the umbilical vein.
AB  - BACKGROUND/AIMS: To achieve complete resection of pancreatic cancer, portal vein
      resection has been performed with increasing frequency at the time of
      pancreaticoduodenal resection (pancreaticoduodenectomy or total pancreatectomy).
      In the meantime, visceral congestion and liver ischemia are of great concern
      during the procedure. We investigated safety of portal vein resection using a
      centrifugal pump-assisted bypass between the superior mesenteric vein and the
      umbilical vein. METHODOLOGY: A retrospective comparison was performed in 49
      consecutive patients who underwent pancreatoduodenal resection with or without
      portal vein resection using the bypass for pancreatic cancer. Twenty-two patients
      underwent portal vein resection using the bypass (group 1). The other 27 patients
      undergoing pancreatoduodenal resection without portal vein resection comprise the
      control group (group 2). RESULTS: Total operative time was 756 +/- 159 min and
      526 +/- 109 min (p<0.001) and median blood loss was 2090 mL and 1200 mL in groups
      1 and 2, respectively. However, the centrifugal pump-assisted bypass allowed
      stable bypass flow, and neither intestinal edema nor ischemic change of the liver
      was observed during portal vein resection and the subsequent reconstruction.
      Postoperatively, the peak postoperative AST, ALT and total bilirubin levels
      showed no significant difference and postoperative day of starting a liquid diet
      was similar between the groups (9.0 +/- 5.4 vs. 9.8 +/- 3.8 days, p=0.48). In
      addition, the rates of morbidity (55% vs. 48%) including biliary and pancreatic
      leak as well as mortality (9% vs. 4%) did not significantly differ between the 2
      groups. CONCLUSIONS: The centrifugal pump-assisted bypass may be useful to
      prevent hepatic ischemia and visceral congestion during portal vein resection
      procedures, resulting in similar postoperative outcomes to the control after
      pancreaticoduodenal resection for pancreatic cancer.

PMID- 15239275
TI  - Risk factors for pancreatitis in patients with anomalous union of
      pancreatobiliary duct.
AB  - BACKGROUND/AIMS: The clinical features of pancreatitis in patients with an
      anomalous union of the pancreatobiliary duct (AUPBD) are unclear. This study
      analyzed the clinical features, pathogenic mechanisms, risk factors, and clinical
      courses after treatment in AUPBD patients. METHODOLOGY: The medical records and
      cholangiopancreatograms of 58 patients with AUPBD and a choledochal cyst
      diagnosed between 1982 and 2001 were retrospectively reviewed. RESULTS: Sixteen
      (27.6%) out of the 58 AUPBD patients experienced pancreatitis. The incidence of
      pancreatitis was significantly higher in those patients with a long (>21mm) and
      wide (>5mm) common channel, a wide diameter of the proximal pancreatic duct
      (>2.5mm), the presence of a filling defect in the common channel, and the
      presence of a pancreatic duct anomaly (p<0.05). A bile duct diversion from the
      pancreatic duct by a choledochal cyst excision prevented the recurrence of
      pancreatitis in most cases. A duodenopancreatectomy was required in some cases.
      CONCLUSIONS: The morphological characteristics of the common channel and
      pancreatic duct contribute to the development pancreatitis in AUPBD patients and
      bile reflux into the pancreatic duct might be the main mechanism of pancreatitis
      in these patients.

PMID- 15239276
TI  - Clinical features of patients with chronic pancreatitis complicated by bile duct
      strictures.
AB  - BACKGROUND/AIMS: Distal bile duct stenosis is relatively rare in patients with
      non-alcoholic chronic pancreatitis. METHODOLOGY: The clinical features of eight
      patients who had chronic pancreatitis complicated by bile duct strictures who
      underwent surgical treatments were reviewed. RESULTS: Ages ranged from 38 to 80
      years, with a mean of 53.4 years. All but one patient were male. Six patients had
      moderate or slight epigastric pain. Five patients had obstructive jaundice and
      underwent biliary drainage. All patients had liver dysfunction due to biliary
      obstruction. Although four of the eight patients were heavy or moderate drinkers,
      none of the patients had a history of chronic pancreatitis. Stricture shapes of
      the common bile ducts were smooth and tapering in five patients, funnel-shaped in
      two, and rat-tail in one. Four patients underwent a pancreatoduodenectomy and one
      patient underwent a pylorus-preserving pancreatoduodenectomy for clinically
      suspected pancreatic malignancy that was later proven histopathologically to be
      chronic pancreatitis. The other three patients underwent a
      choledochoduodenostomy. There were no postoperative complications or deaths.
      During the follow-up period, all patients were asymptomatic. CONCLUSIONS: In
      conclusion, bile duct stricture potentially occurs not only in patients with
      alcoholic chronic pancreatitis but also in patients with nonalcoholic chronic
      pancreatitis. Furthermore, in some cases, it is impossible to differentiate
      chronic pancreatitis from pancreatic or periampullary malignancy.

PMID- 15239277
TI  - Double duct-to-mucosa pancreaticojejunostomy for bifid pancreatic duct.
AB  - We report a pancreaticojejunostomy with double duct-to-mucosa anastomotic
      technique after pyloruspreserving pancreaticoduodenectomy for chronic
      pancreatitis with bifid pancreatic duct. A 49-year-old Japanese man was diagnosed
      preoperatively as having chronic pancreatitis with common bile duct stricture and
      pseudocyst of the pancreatic head. In a pancreaticoduodenectomy, the main
      pancreatic duct (7mm in diameter) and a secondary pancreatic duct (4mm in
      diameter) were identified intraoperatively at the transected surface.
      Pancreatography showed the main pancreatic duct as well as thesecondary
      pancreatic duct that drained the remaining dorsal pancreas, allowing us to
      diagnose bifid pancreatic duct. The pancreaticojejunostomy was performed in an
      end-to-side manner to create double duct-to-mucosa anastomoses and to approximate
      the pancreatic parenchyma and jejunal seromuscular layers. Although bifid
      pancreatic duct is a rare anatomical anomaly, it behooves every surgeon who
      performs pancreatic resections to be aware of this entity and the techniques for
      dealing with it.

PMID- 15239278
TI  - Preaortic paraganglioma mimicking a hypervascular tumor of the pancreas.
AB  - Paragangliomas are rare tumors that arise from neuroepithelial cells. They are
      most frequently located in the para-aortic region and they may be confused with
      other retroperitoneal tumors, especially pancreatic tumors. We present a case of
      a secreting preaortic paraganglioma in a young patient which was mimicking a
      hypervascular tumor of the pancreas, and that was completely resected 5 years
      after the failure of a first attempt to remove the tumor.

PMID- 15239279
TI  - Preoperative assessment of the depth of early gastric cancer invasion by
      transabdominal ultrasound sonography (TUS): a comparison with endoscopic
      ultrasound sonography (EUS).
AB  - BACKGROUND/AIMS: Transabdominal ultrasound sonography (TUS) is considered a
      useful diagnostic tool ascertaining depth of cancer invasion, but there are few
      detailed studies on its accuracy in preoperative estimations of depth of invasion
      in early gastric cancer (mucosal and submucosal cancer). We retrospectively
      analyzed the clinical efficacy of preoperative evaluation by TUS in early gastric
      cancer in comparison with endoscopic ultrasound sonography (EUS). METHODOLOGY: A
      total of 101 patients preoperatively diagnosed as early gastric cancer were
      enrolled in the current study. Patients were given 300cc of water subsequent to
      administration of an anti-peristaltic agent to facilitate filling the gastric
      lesion with water and TUS was performed. All patients were preoperatively
      examined by both EUS and TUS. RESULTS: The depth accuracy in mucosal cancer was
      59% with EUS and 66% with TUS. When submucosal cancers were subdivided into
      shallow and deep submucosal cancers, the depth of mucosal and shallow-submucosal
      (SM1) cancers were correctly assessed 80% and 78% by EUS and TUS, respectively.
      Accuracy increased by 12% in mucosal cancer by combining EUS and TUS diagnoses.
      CONCLUSIONS: The diagnostic value of TUS is comparable to that of EUS in
      assessing depth of invasion of early gastric cancer, however, TUS had a
      possibility of misdiagnosing the depth of tumors located at the anterior wall. To
      ensure an accurate estimation of the depth of tumor invasion, it is recommended
      that TUS and EUS be done simultaneously.

PMID- 15239280
TI  - Endoscopic Doppler ultrasound after injection therapy for peptic ulcer
      hemorrhage.
AB  - BACKGROUND/AIMS: A positive Doppler signal in endoscopic Doppler ultrasound at
      index endoscopy predicts a high risk for rebleeding from peptic ulcer. The aim of
      this study was to evaluate if a negative Doppler status immediately after
      injection therapy may exclude a rebleeding from peptic ulcer in a high-risk
      cohort. METHODOLOGY: Twenty consecutive patients (pts) (age: 68 (33-91) yrs; 11
      female) with peptic ulcer bleeding were enrolled. All patients with an actively
      bleeding ulcer and those with a non-actively bleeding, but Doppler-positive ulcer
      were treated by injection of adrenaline (1:10,000 dilution). Treatment was
      performed during index endoscopy until the Doppler status was negative. Patients
      were followed-up clinically and endoscopically (including Doppler ultrasound) for
      bleeding recurrence. RESULTS: Patients were treated by injection of 12 (6 to 20)
      mL of adrenaline solution until Doppler scan was negative. During follow-up four
      pts (20%) had a clinically overt rebleeding episode. At control endoscopy three
      ulcers were actively bleeding and another two were Doppler positive without
      rebleeding (total: five of eighteen (27.7%) Doppler-positive ulcers). Two of the
      twenty pts required surgical therapy due to rebleeding (10%). CONCLUSIONS: A
      negative endoscopic Doppler status immediately after injection therapy is not
      helpful to identify patients with no risk for rebleeding from peptic ulcer.

PMID- 15239281
TI  - Choice of the surgical treatment in early gastric cancer.
AB  - BACKGROUND/AIMS: The authors report their experience in choosing the surgical
      treatment for early gastric cancer. METHODOLOGY: A retrospective study was
      conducted to examine the long-term outcome of 18 patients with early gastric
      cancer (10%) on a series of 180 patients treated for gastric carcinoma by the
      same surgical equipe from January 1986 to June 1997. Radical surgery with
      gastrectomy and extended lymphadenectomy ("regional" from 1986 to 1991; D2 from
      1992 to 1997) was chosen as standard treatment for early gastric cancer except in
      elderly or high-risk patients and in cases of mucosal tumors diagnosed at
      definitive histology after surgery for benign diseases in which limited surgery
      was performed. RESULTS: All patients received curative (R0) surgery. One patient
      with mucosal-N1 tumor and another one with submucosal-N0 tumor died because of
      gastric cancer at 51 and 42 postoperative months respectively. The mean follow-up
      time was 99.8 (11-193) months. The overall 5-year and 10-year survival rates are
      86.7% and 86.7% respectively. The 5- and 10-year survival rates for intramucosal
      tumors are 91% and 91% respectively and for submucosal cancer are 75% and 75%
      (P=0.39). CONCLUSIONS: According to the prognostic value of nodal involvement and
      the difficulty in achieving a preoperative accurate diagnosis of depth of
      invasion and of nodal involvement in early gastric cancer, a radical gastric
      resection with D2-lymphadenectomy should be performed.

PMID- 15239282
TI  - Reconstructive procedure after distal gastrectomy to prevent remnant gastritis.
AB  - BACKGROUND/AIMS: Gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth
      II) after distal gastrectomy is associated with duodenogastric reflux and remnant
      gastritis. This study sought to determine which reconstructive procedure is least
      likely to cause remnant gastritis and to determine the correlation between
      duodenogastric reflux and remnant gastritis. METHODOLOGY: Sixty patients who
      underwent curative distal gastrectomy for gastric cancer were classified into
      three groups by reconstructive procedure: group A, Roux-Y (n=18); group B,
      Billroth I (n=25); group C, Billroth II (n=17). Intragastric bile reflux was
      monitored using the Bilitec 2000 14 days after surgery, and endoscopy was
      performed and a patient questionnaire was completed 12 weeks after surgery.
      RESULTS: Bile reflux occurred in 23.9%, 40.4%, and 73.4% of the time (p<0.001),
      and remnant gastritis developed in 33%, 76%, and 100% of patients (p<0.001), in
      groups A, B, and C, respectively. Helicobacter pylori infection did not correlate
      with remnant gastritis (p=0.57). Symptoms following Roux-Y reconstruction were
      comparable to those following Billroth I and II reconstructions. CONCLUSIONS:
      Roux-Y reconstruction following distal gastrectomy is superior to Billroth I and
      II reconstruction in preventing remnant gastritis because it reduces
      duodenogastric reflux.

PMID- 15239283
TI  - Undisturbed water gastric emptying in patients of stomach cancer.
AB  - BACKGROUND/AIMS: Gastric cancer is an infiltrative disease involving deep layers
      of the stomach. It is of interest whether the stomach motility in gastric cancer
      patients may be altered. We employed a homemade applied potential tomographic
      system to study the features of water gastric emptying in gastric cancer
      patients. METHODOLOGY: Twelve electrodes were placed in a circular array around
      the upper abdomen of studied subjects. After drinking 500 mL of test water,
      paired electrodes injected an electrical current and another 9 paired electrodes
      recorded signals. This procedure was processed in a rotated order for 50 min
      while the serial changes in altered resistivity were constructed to display water
      gastric emptying curve. Before surgery, 27 histologically confirmed gastric
      cancer patients were enrolled to measure their gastric emptying parameters
      including half emptying time (T1/2) and area under the curve (AUC). Consequently,
      tumor parameters were obtained from their resected specimens. In addition, 28
      healthy controls were recruited to compare water gastric emptying. RESULTS: The
      half emptying times of gastric cancer patients and controls were 15.51 +/- 2.21
      (SE) and 16.82 +/- 2.13 min, respectively (NS). While their measured areas under
      the curve were also comparable (1719.5 +/- 169.4 vs. 1896.0 +/- 143.6 arbitrary
      unit, NS). Regarding with various patient factors to influence water gastric
      emptying among gastric cancer patients, those patients presenting nausea (T1/2:
      8.3 +/- 1.44 vs. 18.5 +/- 2.8 min, P<0.05) or free of regional lymph node
      metastasis (9.98 +/- 2.53 vs. 22.7 +/- 3.84 min, P<0.05) had a rapid water
      gastric emptying. Other demographic and tumor characteristics including gender,
      age, smoking, body size, serum levels of tumor markers, cancer location/size,
      invasion layer, Helicobacter pylori colonization and histological subtype did not
      influence water gastric emptying. CONCLUSIONS: Water gastric emptying in non
      obstructive gastric cancer patients is mainly undisturbed. However, some obvious
      dyspeptic symptom or tumor nature appears leading to a rapid water gastric
      emptying.

PMID- 15239284
TI  - Obesity and outcome of distal gastrectomy with D2 lymphadenectomy for carcinoma.
AB  - BACKGROUND/AIMS: Obesity has correlated with surgical outcome in patients
      undergoing elective surgery for various cancers. This relationship has not been
      examined for gastric cancer surgery performed at a specialized high-volume
      center. METHODOLOGY: Data from 562 consecutive patients treated with potentially
      curative distal gastrectomy between 1993 and 1999 were used. Patients were
      assigned to 2 groups according to a combination of Japanese and Western criteria
      for obesity (group A, body mass index < 25 for men and < 22 for women; or group
      B, body mass index > or = 27). Relationships between obesity and clinical
      variables were analyzed. RESULTS: Two hundred and five patients (29.4%) were
      obese by Japanese cutoff values; only 50 (7.2%) were obese by Western standards.
      A significant difference in blood loss and operative time was noted between
      groups. Intra-abdominal infection was more frequent for group B, leading to
      significantly longer hospitalization. Lymph node yield was significantly smaller
      in group B, but no influence of obesity on long-term survival was observed.
      CONCLUSIONS: Obesity can increase duration of surgery, volume of blood loss, and
      incidence of surgical complications, but does not affect long-term survival.

PMID- 15239285
TI  - A comparative study of pancreatectomy and pancreas-preserving gastrectomy in
      advanced gastric carcinomas.
AB  - BACKGROUND/AIMS: In patients with advanced gastric carcinoma (tumor infiltrating
      beyond submucosal layer), distal pancreatectomy has been frequently performed
      simultaneously with gastrectomy for complete removal of the lymph nodes along the
      splenic artery. However, the possibility of a negative impact has also been
      reported. To evaluate the effects of distal pancreatectomy with gastrectomy for
      patients with advanced gastric cancer, we retrospectively analyzed 84 patients
      who had proximal- or middle-third advanced gastric cancer resected in an
      institution in Taiwan. METHODOLOGY: From 1988 to 1998, 46 patients who underwent
      gastrectomy with distal pancreatectomy (DP group) and 38 patients who had
      pancreas-preserving gastrectomy (PS group) for advanced gastric cancer were
      reviewed. The clinicopathological details and survival rates were compared
      between the two groups. RESULTS: In terms of clinicopathological factors and
      operative mortality, there were no significantly statistical differences between
      the patients who did and did not undergo distal pancreatectomy. The cumulative 5
      year survival rate for the DP group was 35.6%, whereas the 5-year survival rate
      for the PS group was 42.4% (P=0.6224). In contrast, the operative morbidity was
      significantly higher in patients who had distal pancreatectomy (P=0.008).
      CONCLUSIONS: Since distal pancreatectomy does not benefit patients with advanced
      gastric cancer, this procedure should not be regarded as routine in a radical
      resection.

PMID- 15239286
TI  - Total gastrectomy reconstructed by interposition of a jejunal J pouch with
      preservation of hepatic vagus branch and lower esophageal sphincter for T2
      gastric cancer without lymph node metastasis.
AB  - BACKGROUND/AIMS: In order to improve postgastrectomy disorders of patients with
      T2 (MP or SS) gastric cancer without lymph node metastasis, which mainly locates
      in the middle third of stomach, we have performed a total gastrectomy preserving
      both hepatic vagus branches and the lower esophageal sphincter as a function
      preserving surgical procedure. METHODOLOGY: In the present study, the application
      criteria and points of the technique are outlined, and postoperative quality of
      life is clinically investigated. Twenty-four subjects who underwent this surgical
      operation (group A; 16 men and 8 women subjects aged 46 to 73 years, mean age
      62.2 years) were interviewed regarding appetite, weight loss, reflux esophagitis,
      dumping syndrome, and microgastria. Cholelithiasis following total gastrectomy
      was also checked by abdominal ultrasonography. Group A was compared with 26 cases
      of conventional total gastrectomy with D2 lymphadenectomy, excision of lower
      esophageal sphincter, total vagotomy, and single jejunal interposition (B group;
      19 men and 7 women subjects aged 42 to 75 years, mean age 64.8 years).
      Application criteria of the technique: Included were cases with T2 cancer of N0
      mainly localizing at the middle-third of the stomach which was 4 cm or further in
      distance from the oral-side margin of the cancer to the esophagogastric mucosa
      junction. Points of the technique: In lymphadenectomy, hepatic branches of the
      vagal nerve only preserved. To preserve lower esophageal sphincter, the abdominal
      esophagus was severed at the level of His angle to the longitudinal axis of the
      esophagus. Substitute stomach was created as a 15-cm jejunal pouch with a 5-cm
      long jejunal conduit for isoperistaltic movement. RESULTS: In group A the food
      ingestion rate was significantly greater than that of group B (P<0.001) at 6
      months and 2.0 years after operation, with no reflux esophagitis or dumping
      syndrome being noticed at 2.0 years after operation. In group B, loss of appetite
      2.0 years after operation was significantly higher than that in group A (P<0.01).
      In addition, symptomatic reflux esophagitis (heartburn, dyspepsia, regurgitation)
      developed more significantly in group B than in group A (P<0.05). For food
      ingestion per time, group B was significantly delayed compared with group A
      (P<0.05). Body weight loss in group B was significantly higher than that in group
      A (P<0.01). Postgastrectomy cholelithiasis was detected significantly more in
      group B than in group A (P<0.05). CONCLUSIONS: These results suggested that the
      surgical technique proposed is safe and leads to a satisfactory symptomatic and
      nutritional result, and that this procedure is a function-preserving gastric
      surgery appropriate to prevent postgastrectomy disorders of subjects for T2
      gastric cancer without lymph node metastasis, mainly located in the middle-third
      of stomach.

PMID- 15239287
TI  - Correlation between duodenogastric reflux and remnant gastritis after distal
      gastrectomy.
AB  - BACKGROUND/AIMS: Many patients who undergo distal gastrectomy develop remnant
      gastritis. This report describes the correlation between remnant gastritis and
      the amount of duodenogastric reflux and looks at the relationship between
      Helicobacter pylori infection and duodenogastric reflux in remnant gastritis.
      METHODOLOGY: Sixty-two patients who underwent curative distal gastrectomy for
      gastric cancer with radical lymphadenectomy were studied. The period of bile
      reflux (percent time) into the gastric remnant was measured with the Bilitec 2000
      under standardized conditions. Remnant gastritis was semi-quantified using the
      neutrophil infiltration score based on the updated Sydney System, and the
      presence of H. pylori infection was determined 12 weeks after the surgery.
      RESULTS: Overall, the correlation was not significant between the neutrophil
      infiltration score and the percent time (p=0.08). Similarly, the correlation was
      not significant in patients with H. pylori infection (p=0.30), but it was
      significant in patients without H. pylori infection (p=0.03). CONCLUSIONS:
      Duodenogastric reflux after distal gastrectomy can cause remnant gastritis in
      patients without H. pylori infection. Reconstruction with biliary diversion is
      protective against the development of remnant gastritis.

PMID- 15239288
TI  - Adjuvant chemotherapy in a unique population of patients with gastric cancer
      undergoing surgery.
AB  - BACKGROUND/AIMS: Total gastrectomy with D2 dissection theoretically removes the
      gross primary tumor with its potential route of dissemination, that is
      locoregional lymph nodes. Complementary therapy for the control of systemic
      microscopic disease should be taken into consideration in patients whom surgery
      with curative intent was performed. METHODOLOGY: Twenty-eight patients with
      moderately differentiated, locally advanced gastric carcinoma underwent total
      gastrectomy with D2 lymph node dissection. The operative mortality rate was 0% in
      this series. Fifteen patients received six courses of adjuvant 5-FU + leucovorin
      in doses of 425 mg/m2/d and 20 mg/m2/d respectively in five-day cycles month ly.
      The remaining 13 patients constituted the control (surgery only) group. RESULTS:
      The mean disease-free and overall survival rates were 41 and 48 months (p: 0.78)
      and 42 and 53 months (p: 0.43) in the control and chemotherapy groups,
      respectively. The odds ratio for crude mortality was 0.7. CONCLUSIONS: Although
      statistical significance has not been achieved in this study, a trend toward
      adjuvant chemotherapy has emerged in that unique group of patients with
      moderately differentiated (intestinal type) adenocarcinoma of the stomach
      undergoing curative surgery.

PMID- 15239289
TI  - Benefits of a dedicated cystic fibrosis pharmacist.

PMID- 15239292
TI  - The nature and prevalence of eating disorders and eating disturbance in
      adolescents with cystic fibrosis.

PMID- 15239290
TI  - Physiotherapy in infants and young children with cystic fibrosis: current
      practice and future developments.

PMID- 15239293
TI  - Changing behaviour: using motivational interviewing techniques.

PMID- 15239291
TI  - Understanding cystic-fibrosis-related diabetes: best thought of as insulin
      deficiency?
AB  - The limited available evidence supports the use of insulin treatment in CFRD.
      This fits with the dominant problem in CFRD being insulin deficiency and
      progressive beta cell dysfunction, making tablets that stimulate the beta cell
      unlikely to be a successful strategy. It is possible that patients with IGT or
      CFRD with moderate hyperglycaemia (e.g. relative preservation of fasting glucose)
      may initially respond to beta cell secretagogues. A large randomized prospective
      trial in the USA should answer this point in the next few years.

PMID- 15239294
TI  - Vitamin K in cystic fibrosis.

PMID- 15239295
TI  - The potential for stem cell therapy in cystic fibrosis.

PMID- 15239296
TI  - Newborn screening for cystic fibrosis: the practical implications.

PMID- 15239297
TI  - Potential benefits of the UK Cystic Fibrosis Database.

PMID- 15239298
TI  - An institutional outbreak of leptospirosis in Chennai, South India.
AB  - The emergence of an outbreak of leptospirosis in a nurses' hostel in Chennai
      presented a challenge to identify and control the source of the outbreak. Sixty
      nine residents and staff members were interviewed to assess exposure factors.
      Blood samples from the acute and convalescent patients were tested with the
      Microscopic Agglutination Test using the serovars prevalent in Chennai.
      Polymerase Chain Reaction (PCR) was conducted on serum and water samples. Based
      on preliminary investigation, control measures with standard hygienic measures
      were instituted. The attack rate was 35%. The epidemic curve suggested continuous
      or intermittent exposure to infection over a five-week period. Twenty residents
      (three asymptomatic) developed laboratory confirmed Leptospira
      icterohemorrhagiae. Residents collected water from an underground storage tank
      that was filled twice weekly from a mobile water tanker with a bucket on a rope,
      and the tank was usually left open. PCR tests confirmed the presence of
      leptospires from this water. Other control measures included cleaning the large
      backyard with its many stray dogs and rats, chlorinating water supplies, boiling
      drinking water and health education. No further cases occurred twelve days after
      implementing control measures. Access to clean water, not only for drinking but
      also for bathing, brushing and washing is essential to prevent water-borne
      outbreaks.

PMID- 15239299
TI  - A qualitative study on the feasibility and benefits of foot hygiene measures
      practiced by patients with brugian filariasis.
AB  - Disability alleviation is an important component of 'Global Programme for
      Elimination of Lymphatic Filariasis'. In Brugia malayi infection the disability
      is largely due to acute attacks of adenolymphangitis (ADL), which frequently
      prevent patients from attending their normal activities, causing much suffering
      and economic loss. The foot care programme has been shown to reduce the frequency
      and severity of these episodes. In the present study we used semi-structured
      interviews to evaluate the impact of the foot care in 127 patients with brugian
      filariasis. They were previously trained in this procedure and were advised to
      practice it regularly, unsupervised. All except one could recollect the various
      components of foot hygiene and were practicing it regularly. They were aware of
      the factors causing ADL attacks and were able to avoid them. Majority (95.2%)
      expressed their happiness with the relief provided by foot care, which prevented
      or reduced the ADL episodes. The motivation was such that they transmitted this
      knowledge to others suffering in the community and even physically helped them to
      carry out foot care. This study fully endorses the advocacy of foot care
      programme as an easy to carry out, effective, sustainable and economically
      feasible procedure to prevent acute ADL attacks.

PMID- 15239300
TI  - Bacteriophage typing and antibiotic sensitivity pattern of Staphylococcus aureus
      from clinical specimen in and around Solapur (South Maharashtra).
AB  - Two hundred and eighty nine strains of Staphylococcus aureus isolated from pus
      and wound swabs (149), blood (36), urine (28), sputum (14), stool (12), throat
      swab (9) and CSF (4) were subjected for bacteriophage typing and antibiotic
      susceptibility pattern. 113 (39.11%) strains were typable. Among the typable
      strains, 16 (5.53%) belonged to phage group I, 33 (11.41%) strains belonged to
      phages group II, 38 (13.14%) belonged to phage group III, 26 (8.99%) strains
      belonged to the phages which have not been allocated to any group (Miscellaneous
      group) 176 (60.89%) strains were untypable. Only one (0.34%) strain was sensitive
      to all the drugs tested. Almost all the isolates were resistant to Ampicillin and
      Tobramycin (99.3% each). 286 (98.96%) strains were found to be resistant to
      Penicillin and Erythromycin followed by Kanamycin 272 (94.11%) and Gentamicin 263
      (91.3%). 113 (39.1%) strains were Methicillin resistant Staphylococcus aureus
      (MRSA). All MRSA strains were resistant to all drugs tested except vancomycin.
      Resistance to most of the commonly used antimicrobial agents indicates a need to
      replace these drugs with other agents and maintenance of surveillance to detect
      changing patterns of resistance.

PMID- 15239301
TI  - A passive haemagglutination test for rabies antibodies using rabies glycoprotein
      coupled erythrocytes.
AB  - The presently recommended tests for assaying rabies antibodies like mouse
      neutralization test (MINT) and rapid fluorescent focus inhibition test (RFFIT)
      are either time consuming or expensive and are generally performed in reference
      laboratories. There is a need to develop a specific and rapid method for
      detection of rabies antibodies that can be used to monitor sero-conversion after
      pre-or post-exposure vaccination. In this study, we have developed a passive
      haemagglutination (PHA) using purified rabies virus glycoprotein coupled to sheep
      erythrocytes using chromium chloride (0.04%) as a coupling agent. Two hundred and
      fifty five serum samples from people vaccinated with different rabies vaccines,
      16 paired serum and CSF samples from autopsy confirmed cases of paralytic rabies,
      and serum samples from 65 normal healthy controls were tested and evaluated in
      comparison to standard MNT. Among the vaccinees, 250 samples were positive both
      by MNT and PHA but 5 samples were negative by PHA and positive by MNT. The titres
      obtained by PHA were lower compared to MNT, but there was significant correlation
      between the two (r=0.885). The specificity of the test was 99.7% and sensitivity
      was 100% as compared to MNT. Thus this PHA test promises to be a rapid and
      specific test for assaying rabies antibodies and may be useful in screening large
      number of serum samples for sero conversion after vaccination. It may also assist
      in rapid laboratory confirmation of paralytic rabies cases, based on detection of
      antibodies in CSF and serum.

PMID- 15239302
TI  - Comparison of direct immunofluorescence and ELISA for the detection of Chlamydia
      trachomatis antigen in the patients of pelvic inflammatory disease.
AB  - Fifty female patients clinically diagnosed as pelvic inflammatory disease (PID)
      attending Gynaecology OPD of Smt. Sucheta Kriplani Hospital were studied for the
      presence of Chlamydial antigen by direct immunofluorescence (DFA) and Enzyme
      linked immunosorbant assay (ELISA) test. Out of fifty PID patients Chlamydia
      tracchomatis lipopolysaccharide antigen could be detected in 28% of cases by
      ELISA and Chlamydial outer membrane protein antigen could be detected in 32% of
      cases by DFA. Although in the present study DFA and ELISA compare well with each
      other, but DFA has been found to be more specific test as it detects outer
      membrane protein antigen of Chlamydia trachomatis.

PMID- 15239303
TI  - Treatment of microfilaraemics with DEC and its effect on vector infection and
      infectivity in tribal and non-tribal areas of Bankura district, West Bengal,
      India.
AB  - Single course DEC treatment (6 mg/kg body weight/day for 12 days) was
      administered to 66 tribal and 442 non-tribal microfilaria (mf) carriers detected
      through a Filariasis survey in Bankura district, West Bengal, India. All the mf
      carriers remained amicrofilaraemic on 22nd, 180th and 365th post-treatment day.
      As a result of DEC treatment to the mf carriers, vector (Culex quinquefasciatus)
      infection rate in tribal study areas reduced from 2.06% to 1.07%. Infectivity
      rate was "nil" both before and after treatment. In non-tribal study areas, vector
      infection rate reduced from 4.33% to 2.22% and infectivity rate from 0.51% to
      0.29%.

PMID- 15239304
TI  - A focal outbreak of Japanese Encephalitis among horses in Pune district, India.

PMID- 15239305
TI  - Mosquito larvicidal properties of the leaf extract of a herbaceous plant, Ocimum
      canum (Family: Labiatae).

PMID- 15239306
TI  - Prevalence of fluorosis in the villages of district Nawada, Bihar and Palamu,
      Jharkhand.

PMID- 15239307
TI  - Fluorosis in rural areas of Alwar district.

PMID- 15239308
TI  - Susceptibility status of Phlebotomus argentipes to insecticides in districts
      Vaishaii and Patna (Bihar).

PMID- 15239309
TI  - A study on the breeding habitats of Aedes species around Visakhapatnam sea port.

PMID- 15239310
TI  - Japanese Encephalitis situation in Gorakhpur division, U.P.

PMID- 15239312
TI  - ACEN update: Canadian nursing leadership study.

PMID- 15239313
TI  - ACEN position statement: Nursing workload--a priority for healthcare.

PMID- 15239314
TI  - New strategies for developing leadership.

PMID- 15239315
TI  - Collaborative practice in health systems change: the Nova Scotia experience with
      the Strengthening Primary Care Initiative.
AB  - Recently attention has been focussed on the significance of primary care to the
      Canadian healthcare system. Nova Scotia. Like other provinces, is seeking ways to
      improve the healthcare that it provides within a financially constrained publicly
      funded system. The Strengthening Primary Care Initiative in Nova Scotia (SPCI)
      was a primary care demonstration project to evaluate specific goals related to
      primary care. Although the provincial government conceived the SPCI, the approach
      to its planning and implementation was participatory and consultative. Funded
      through the federal Health Transition Fund (HTF) (Health Canada 2002) and the
      government of Nova Scotia, the SPCI involved changes in four communities over a
      three-year period (2000-2002). These changes included the introduction of a
      primary healthcare nurse practitioner in collaborative practice with one or more
      family physicians; remuneration of the family physician(s) with methods other
      than a solely fee-for-service (FFS) arrangement; and the introduction and
      utilization of a computerized patient medical record. The SPCI was committed to a
      consultative process with stakeholders, and this gave rise to several challenges.
      Initially there was disagreement on the requirement for nurse practitioners at
      each of the demonstration sites. The Minister of Health confirmed that a nurse
      practitioner was a required component at each demonstration site. Differences in
      perspectives on the role of allied health professionals in the SPCI were
      encountered, and the significance of the role pharmacists have in primary care
      was not fully appreciated until after the SPCI had started. At the time the SPCI
      began there was no legislation for nurse practitioners in Nova Scotia; therefore,
      an approval mechanism for nurse practitioner practice was authorized through the
      provincial regulatory bodies for nursing and medicine. Malpractice and liability
      issues, particularly on the part of providers who had never worked with nurse
      practitioners before, were an initial concern. Recruitment of nurse practitioners
      into the three rural sites mirrored the difficulties with recruitment of
      healthcare providers encountered in other parts of rural Canada. The authors
      discuss their perspectives on the challenges related to interdisciplinary
      collaboration in health systems change that were encountered during the planning
      and implementation of the SPCI. Although nurse practitioner Legislation has
      existed in Ontario and Newfoundland and Labrador for several years, many
      provinces are grappling with the challenges associated with the introduction of
      nurse practitioners and collaborative practice. This paper conveys the experience
      of one province and will be of interest to administrators, educators and
      practitioners elsewhere in Canada who are engaged in primary healthcare renewal.

PMID- 15239316
TI  - Commentary: Nurses lead the way....

PMID- 15239317
TI  - Dancing to our own tune: understandings of advanced nursing practice in British
      Columbia.
AB  - There has been ongoing confusion about the meaning of advanced nursing practice
      (ANP) and the nature of ANP roles in Canada and elsewhere. A broad range of roles
      and titles have been adopted throughout Canada in an attempt to delineate
      specialized and/or advanced roles within nursing. One key objective in a recent
      three-phase study of ANP in British Columbia was to clarify the role and
      understanding of advanced nursing practice and related roles within the larger
      healthcare system. Our intent in this paper is to describe the understandings of
      ANP that emerged in Phase I of this recent study and to compare registered
      nurses' understandings of ANP to the characteristics and competencies identified
      by the Canadian Nurses Association (2002) framework. (Note: The term "nurse," as
      used in this paper, refers to "registered nurse.") We conclude by identifying
      future directions for development of advanced practice roles.

PMID- 15239318
TI  - Commentary: A nurse by any other name is still a nurse.

PMID- 15239319
TI  - Retaining and transferring nursing knowledge through a hospital internship
      program.
AB  - In healthcare, organizations recognize that human capital is their most valuable
      asset. The importance of investing in knowledge workers is imperative given the
      current and future shortage of health professionals. Knowledge acquisition occurs
      through continuous learning and the transfer of information from those who are
      highly experienced to those who are less qualified. At St. Michael's Hospital,
      two innovative and unique programs were created for the transfer of knowledge.
      The first was a nurse fellowship program that enabled experienced nurses to spend
      two to three months learning new skills to advance clinical practice. The second
      was a nurse internship program in which new graduates spend three to four months
      in their area of hire to enhance clinical practice through skill development and
      prioritization of patient care needs. This paper describes both programs and
      presents an evaluation of the new-graduate internship program as an opportunity
      for professional development and career enhancement For nurse interns, the
      program promotes self-esteem and professional confidence, improves job
      satisfaction and rewards nurses for their contribution. For nurse preceptors, the
      program provides job enrichment, experience in teaching and recognition by the
      organization and peers that they are knowledge experts. In healthcare,
      organizations have come to acknowledge that their most valuable asset is human
      capital, in particular, knowledge workers (Horibe 1999). Knowledge workers
      contribute a composite of information, intellectual property and experience
      (Horibe 1999), acquired by study, investigation, observation or practice
      (Webster's Dictionary 1989). Investing in knowledge workers is investing in the
      future. In this regard, organizations have implemented recruitment and retention
      strategies to attract, retain and advance the highest calibre of health
      professional. Knowledge workers contribute to an organization through their
      ideas, analyses of complex situations and sound judgment in decision-making
      (Horibe 1999). They further develop these skills over the course of their career
      through continuous learning. This paper will focus on the importance of investing
      in nurses as knowledge workers. In particular, given the shortage of nurses and
      the reality that 25% of today's nurses can retire over the next 10 years (CNA
      2001), it is imperative that knowledge transfer occur from highly experienced to
      less experienced nurses.

PMID- 15239320
TI  - Leading towards the future: implementing nursing leadership principles at the
      front line.
AB  - Federal and provincial professional bodies of nursing and healthcare are
      examining the role of nursing leadership and its relation in creating and
      sustaining quality work environments for nursing. Using the findings and
      recommendations of the Canadian Nursing Advisory Report Committee (2002) as a
      catalyst, nurse leaders from Children's and Women's Health Centre of British
      Columbia (C&W) have collaborated to develop principles of nursing leadership to
      be used as a resource in determining roles and functions of front-line nurse
      leaders throughout the organization. In this paper, the process of creating those
      nursing leadership principles is described with a focus on the unit-based
      operational leader. Suggestions are made on how to evaluate the effectiveness of
      principle-based nursing leadership as implemented at C&W and its utility to the
      unit-based operational leader.

PMID- 15239321
TI  - The impact of hospital restructuring on home care nursing.
AB  - BACKGROUND: Health reform in many industrialized countries has prompted the shift
      from institutional to community care. In Ontario, this approach was instigated
      through the Health Services Restructuring Commission. OBJECTIVES: The purpose of
      this study was to determine whether changes in the hospital sector between 1996
      and 2000 resulted in changes in the provision of home-care services by nurses and
      practical nurses. METHODS: This study was a retrospective trend analysis of
      linked hospitalization and home-care utilization data for Kingston for 1996 to
      2000. The measures include the rate of home care and the volume and intensity of
      home-care services. RESULTS: Between 1996 and 2000 there was a net 4% increase in
      the age-gender standardized rate of admission to home-care nursing services, with
      a 10% rate rise between 1996 and 1997. The total volume of home-care services
      increased during the study, as did the average intensity of home-care service
      delivery over the first month post-hospitalization during the first four years.
      This article will give readers their first look at the changes in home-care
      nursing following hospital restructuring in Kingston.

PMID- 15239322
TI  - The value of our practice.

PMID- 15239323
TI  - Do you smell that?

PMID- 15239324
TI  - Verbal abuse.

PMID- 15239325
TI  - Latex precautions for tissue.

PMID- 15239326
TI  - Minimally invasive total hip arthroplasty.
AB  - Total hip arthroplasty procedures relieve patients' arthritic hip pain. Since the
      first procedure was performed in the 1960s, surgeons and implant companies have
      worked to improve prosthesis design, composition of implants, and the mechanisms
      for holding the implants in place. Recently, surgeons have focused on minimizing
      the surgical incision. Smaller incisions have resulted in smaller scars and
      faster recoveries. This article presents a brief historical overview of, as well
      as current trends in, minimally invasive total hip arthroplasty. All aspects of
      care for a patient undergoing total hip arthroplasty are discussed.

PMID- 15239327
TI  - Nurses' advocacy in an Australian operating department.
AB  - Acting as a patient advocate in the OR is challenging for many nurses. Personal,
      professional, and organizational barriers to effective advocacy exist, and the
      term advocacy is not clearly defined in the context of nursing practice. Findings
      from an ethnographic study conducted in an Australian operating department shed
      light on the way in which nurses experience the role of patient advocate in the
      OR. This article explores nurses' perceptions of the barriers they face as
      patient advocates and the strategies used to address these barriers.

PMID- 15239328
TI  - Emergency preparedness--is your OR ready?
AB  - Emergency situations only recently have come to include terrorist threats, such
      as radiation, biological and chemical attacks, and bombings. The importance of
      emergency preparedness in health care facilities has increased as a result of
      recent terrorist threats. Perioperative leaders must meet the challenge of
      preparing their departments for a wide range of potential disasters. This article
      describes how a facility can prepare for both natural and man-made disasters and
      reviews modifications to the Joint Commission on Accreditation of Healthcare
      Organizations' disaster preparedness standards.

PMID- 15239329
TI  - The emergence of a business imperative in surgical services.
AB  - In past years, scant attention was paid to the demand and rigors of the business
      of surgical services, and the primary role of nurse managers was as professional
      staff managers. Challenges from the past few years demand the development of a
      more focused approach to the business of surgery. The University of Washington
      Medical Center, Seattle, met this demand by hiring a business manager for the
      surgical services department.

PMID- 15239330
TI  - A critical partnership--safety for nurses and patients.

PMID- 15239331
TI  - Providers of first assisting services.

PMID- 15239332
TI  - [Cyclo-oxygenase 2 inhibitors and cancer].

PMID- 15239333
TI  - [Cyclooxygenase 2 and carcinogenesis].
AB  - The membrane glycoprotein Cox2 is regulated at transcriptional and post
      transcriptional levels by pro-inflammatory agents, cytokines, growth factors,
      oncogenes, and tumor-promoters. Cox2 is expressed during early stages of
      colorectal carcinogenesis from the premalignant adenoma stage, and
      adenocarcinomas of stomach, colon, breast, lung and prostate. Its expression is
      detected in neoplastic, inflammatory, endothelial and stromal cells. Cox2 is
      involved in the conversion of arachidonic acid into prostaglandins and
      thromboxanes, as well as the synthesis of malonaldehyde (MDA, a mutagen) and the
      production of hydrogen peroxide, which promotes carcinogenesis. The Cox2 products
      act in turn on serpentine receptors coupled to heterotrimeric G-proteins (R-TXA2,
      R-PG) that are connected to signaling elements implicated in oncogenesis. Thus,
      Cox2 plays a key role in early stages of carcinogenesis by promoting the
      proliferation of tumoral cells and their resistance to apoptosis, as well as
      angiogenesis. tumor cell invasion and setting up of the metastatic process. These
      mechanisms establish the rationale behind the therapeutic targeting of Cox2 in
      human solid tumors.

PMID- 15239334
TI  - [Cyclooxygenase 2 inhibitors and cancer chemoprevention].
AB  - Chemoprevention is the use of natural or synthetic compounds in order to reverse.
      suppress or prevent the carcinogenic process. Among the many pathways
      dysregulated during the carcinogenic process, cyclooxygenase-2 (Cox2) seems to be
      one of the most promising pathways to target in order to achieve chemopreventive
      and anticancer effects. Indeed, Cox2 overexpression contributes to the
      carcinogenic by at least 5 different mechanisms including transformation of
      procarcinogens on carcinogens, pro-inflammatory and immunomodulatory effect,
      resistance to apoptosis, angiogenesis and invasion progression... This review
      will focus on the rationale and the ongoing research areas related to
      chemopreventive approaches targeting Cox2.

PMID- 15239335
TI  - [Cyclooxygenase 2 inhibitors and adenomatous polyposis coli].
AB  - Prolonged use of aspirin and/or non-steroidal anti-inflammatory drugs induces a
      partial regression of either sporadic adenomas or adenomas in adenomatous
      polyposis coli (APC), but also their emergence and colonic cancer development in
      sporadic adenomas. Specific inhibitors of cyclooxygenase of type 2 (Cox2) induce
      less upper and lower digestive tract adverse events that non-specific anti
      inflammatory drugs. This better tolerance might allow a long-lasting use in
      patients with APC. At time, we don't know if such treatments are able to prevent
      the development of cancer in the rectum or duodenum of these patients. In this
      paper we will discuss the scientific proofs and potential interest of Cox2
      inhibitors in the treatment of PAF.

PMID- 15239336
TI  - [Cyclooxygenase 2 inhibitors and colorectal cancer].
AB  - Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable
      in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in
      vitro and in vivo showed that Cox2 plays a key role in the multistep process of
      colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and
      angiogenesis induction. So that Cox2 represent a potential molecular target in
      colorectal management and specific Cox2 inhibitors may be useful as
      chemopreventive as well as therapeutic agent in humans. In animals study Cox2
      inhibitors was shown to be effective and in humans Cox2 inhibitors are approved
      by the Food and Drug Administration as an adjunct to endoscopic surveillance and
      surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of
      this article is to review the relationship between Cox2/Cox2 inhibitors and
      differents signaling pathways of colorectal carcinogenesis and to precise their
      possible molecular mechanisms of action. This work although review clinicals data
      of their efficacy as chemopreventive agent as well as therapeutic in the
      differents group at risk for colorectal cancer.

PMID- 15239337
TI  - [Cyclooxygenase 2 and breast cancer. From biological concepts to therapeutic
      trials].
AB  - Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role
      in mammary carcinogenesis. Several connections were demonstrated between Cox and
      a few oncogenes (v-src, v-Ha-ras, HER-2/neu, Wnt, p53 mutated), alimentary
      products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins
      [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB
      receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase,
      alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor
      (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No
      correlation of Cox2 expression with hormonal receptors was shown. In
      epidemiologic studies there is evidence of breast cancer risk reduction for women
      who take AINS for a long time. Alimentary factors like resveratrol or insaturated
      fat acid reduce Cox2 expression in animal and could be investigated in human
      studies. Clinical trials are planed with the anti Cox2 celecoxib for breast
      cancer prevention, in adjuvant setting, in metastatic situation combined with
      exemestane or antitubulin drugs or in neoadjuvant therapy.

PMID- 15239338
TI  - [Cyclooxygenase 2 inhibitors and lung carcinoma].
AB  - Cyclooxygenase-2 (Cox2) may play a crucial role in lung carcinogenesis. In fact,
      overexpression of Cox2 is common in non-small cell lung cancer (NSCLC) and seems
      to be associated with tumor progression, invasion and metastasis. In experimental
      animal models Cox2 has been shown to be involved in tumor angiogenesis,
      suggesting that Cox2 is a potential target for NSCLC therapy. Several in vivo
      studies have already shown that Cox2 specific inhibitors (celecoxib, rofecoxib)
      have anti-tumor activity and clinical trials using Cox2 inhibitors are currently
      ongoing in patients with NSCLC.

PMID- 15239339
TI  - [Cyclooxygenase 2 inhibitors and urologic and gynaecologic cancers].
AB  - PGE2 is one of the most important prostaglandin involved in the oncogenesis. PGE2
      is found at high concentration level in the most of epithelial cancer. Urologic
      and gynaecologic cancer express the enzyme which are at the origin of PGE2:
      cyclooxygenase 2. Cox2 inhibitors present anticancer properties demonstrated in
      wide varieties of cellular and animal models. Human applications are currently
      tested in many clinical trials for bladder, prostate and uterine carcinomas.

PMID- 15239340
TI  - [Safety of selective inhibitors of inducible cyclooxygenase-2 taken for a long
      period].
AB  - The serious digestive side effects of the selective inhibitors the inducible
      cyclooxygenase-2 are reduced by 60% as compared to the nonselective non-steroidal
      anti-inflammatory drugs. The main risk factors associated with gastro-intestinal
      ulcers caused by the latter were found also with the selective inhibitors taken
      for long period (age > 60 years, antecedents of gastro-duodenal ulcers,
      concomitant aspirin treatment). In contrast, H. pylori infection was not found as
      risk factor apart from past history of gastro-duodenal ulcers. The complications
      in the lower digestive tract are twice less frequent with the selective
      inhibitors than with nonselective anti-inflammatory drugs. Nevertheless, it seems
      that the risk of exacerbation of inflammatory colitis is not reduced. The
      cardiovascular complications are discussed. Rofecoxib taken at supra-therapeutic
      dosage was recognised to increase the incidence of myocardial infarction. A such
      increase was not found with usual dosage or with celecoxib. The selective
      inhibitors may reduce the renal sodium excretion and increase the blood pressure,
      particularly in hypertensive patients whose the blood pressure has to be
      regularly checked.

PMID- 15239341
TI  - [Analgesic effects of cyclooxygenase 2 inhibitors].
AB  - Traditional pain management strategies for cancer pain have relied on the use of
      opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant
      analgesics. However, the substantial adverse effects associated with their use
      has left many patients without dependable options for effective treatment. Recent
      advances in the understanding of pain and its pathophysiologic mechanisms have
      led to the development of novel therapeutics. Cyclooxygenase(Cox)-2-specific
      inhibitors (coxib) have an established efficacy in the treatment of chronic and
      acute pain comparable to that of traditional NSAIDs without the degree of
      gastrointestinal complication or the platelets inhibitor effect of traditional
      NSAIDs. Numerous studies have shown that coxibs are efficacious in the management
      of chronic and acute pain in various clinical settings including postoperative
      pain. The superior safety profile of coxibs in conjunction with a comparable
      efficacy to nonselective NSAIDs supports the use of coxibs in balanced analgesic
      regimens and provides the potential to incorporate coxibs into the pain
      management algorithm used to treat cancer pain.

PMID- 15239342
TI  - [A method for studying spinal reflex arcs among muscles in the human upper limb:
      a post-stimulus time-histogram technique].
AB  - A post-stimulus time-histogram (PSTH) technique has been used for studying spinal
      reflex arcs in humans. In the PSTH technique, effects of the reflex arcs on the
      motoneuron excitability are examined by analyzing changes in firing probabilities
      of a motor unit after conditioning stimuli to afferent fibers. Recent studies
      with the PSTH technique have demonstrated reflex arcs mediated by low threshold
      muscle afferent fibers (group I afferents) among muscles in the human upper limb.
      The results have shown several differences of the reflex arcs between the human
      upper limb and animal forelimb. This paper has described the PSTH technique.
      Comparisons of the reflex arcs between humans and animals have been also
      described.

PMID- 15239343
TI  - [Comparison of anatomical terms from Basle nomina anatomica to Terminologia
      anatomica--terms of general anatomy].
AB  - This paper compared and considered terms of general anatomy from the Basle Nomina
      Anatomica (1895) to the Terminologia Anatomica (1998), together with the Jena
      Nomina Anatomica (1935). Some differences are found in ideas of the BNA-NA3, NA4
      6 and TA. It was noticed after the NA4, that the "coronalis" was used for the
      site and the "frontalis" for the direction in head, that the term of line and
      plane was reasonably rearranged, and that some terms were omitted from the part
      of human body and moved to the systemic anatomy in head and trunk and to the
      region in limbs.

PMID- 15239344
TI  - Robert Hall More, M.D., M.Sc.: a pioneer of modern pathology in Canada (1912
      2003).

PMID- 15239345
TI  - Relationship between MUC5AC and altered expression of MLH1 protein in mucinous
      and non-mucinous colorectal carcinomas.
AB  - The main purpose of this study was to examine the expression of mucins and
      mismatch repair proteins in colorectal carcinomas. The immunohistochemical
      distribution of apomucins MUC2, MUC5AC, and the expression of MLH1 and MSH2
      proteins were examined in 76 mucinous and 60 non-mucinous colorectal carcinomas.
      MUC2 was noted in all mucinous carcinomas, whereas MUC5AC was present in 41 cases
      only (54%). In non-mucinous carcinomas, MUC2 was expressed in 61.7% of the
      tumors; by contrast, MUC5AC was present in 20% of the cases. The expression level
      of apomucins was significantly different in mucinous and non-mucinous lesions
      (p<0.001). Twenty-seven (35.5%) of the mucinous carcinomas showed no MLH1
      expression, whereas 11 (18.3%) of the non-mucinous tumors did. This difference
      was statistically significant (p<0.005). Altered expression of MSH2 protein was
      never observed. The lack of MLH1 expression was considerably more frequent in
      carcinomas with secretion of MUC5AC (p<0.005). Our study has demonstrated this
      close relationship by immunohistochemical methods. In summary, our data show: (1)
      differences in the expression of mucins between mucinous and non-mucinous tumors;
      (2) a high frequency of altered MLH1 protein expression (35.5%) in mucinous
      carcinomas; (3) a significant relationship between the presence of MUC5AC and the
      altered expression of MLH1 protein in colorectal carcinomas.

PMID- 15239346
TI  - Prognostic significance of matrix metalloproteinase-2, cathepsin D, and tenascin
      C expression in colorectal carcinoma.
AB  - Matrix metalloproteinase-2 (MMP-2) and cathepsin D (CD) play a significant role
      in degrading the components of basement membrane and extracellular matrix (ECM),
      whereas tenascin-C (TN-C) is a glycoprotein of the ECM related to cell adhesion
      and detachment. These proteins have been implicated in tumor invasion and
      metastasis. Therefore, we aimed at investigating the prognostic significance of
      MMP-2, CD, and TN-C expressions in primary colorectal cancer. Overall, 112
      colorectal adenocarcinomas were included in the present study. MMP-2, CD, and TN
      C expressions were evaluated by immunohistochemistry and correlated with
      clinicopathologic prognostic parameters and survival. Diffuse stromal TN-C
      immunostaining was found to be significantly correlated with advanced stage and
      shorter survival time (p = 0.002 and 0.02, respectively). MMP-2 expression was
      found to correlate with lymph vessel invasion (p = 0.006) and stage (p = 0.03).
      CD expression was related to depth of invasion (p = 0.005). No significant
      relationship was found between survival and MMP-2 and CD expression (p > 0.05).
      In multivariate analysis, stage and vascular invasion were independent prognostic
      factors, whereas TN-C did not retain a clear independent relationship to survival
      (p > 0.05). Our findings suggest that TN-C expression may be a potential
      prognostic marker in colorectal carcinoma. However, MMP-2 and CD do not appear to
      be significant indicators of survival.

PMID- 15239347
TI  - The importance of cyclin D1 and Ki67 expression on the biological behavior of
      pancreatic adenocarcinomas.
AB  - The aim of this study was to evaluate the role of cyclin D1 and Ki67 proteins
      involved in cell-cycle control as a prognostic factor in pancreatic carcinomas.
      We examined formalin-fixed, paraffin-embedded material from 59 pancreatic
      adenocarcinomas, for which appropriate clinical and prognostic data were
      available. The standard streptavidin biotin immunoperoxidase method was used for
      immunostaining with cyclin D1 and Ki67. The extent of positive nuclear and
      cytoplasmic cyclin D1 staining was graded semiquantitatively. Ki67 reactivity was
      quantified and expressed as the percentage of stained nuclei. Staining with
      cyclin D1 and Ki67 was compared with histopathological prognostic features, and
      their relation with survival was also tested statistically. Patients whose tumors
      were cyclin D1-positive showed perineural invasion significantly more frequently
      than did patients with cyclin D1-negative tumors at the immunohistochemical
      level. In addition, tumors with lymphatic vessel invasion and without showed a
      significant difference in terms of cytoplasmic cyclin D1 staining. Ki67 indices
      were statistically different in stage groups. There was a significant and direct
      correlation between Ki67 index and nuclear cyclin D1 staining scores. No relation
      with survival was found. Our results suggest that cell-cycle proteins do not
      directly affect the prognosis of patients with pancreatic adenocarcinoma.
      Conversely, cyclin D1-positive tumors tend to have perineural invasion more
      frequently. In addition, lymph vessel invasion is another factor related to
      cyclin D1 reactivity of the cells. Ki67 indices differ statistically in stage
      groups.

PMID- 15239348
TI  - Coexpression of hepatocyte growth factor and its receptor c-Met correlates with
      high MIB-1 proliferative index in malignant fibrous histiocytoma.
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine that variably
      affects cell motility, proliferation, and morphogenesis. Little information is
      currently available on the HGF and its receptor c-Met expression in malignant
      fibrous histiocytoma (MFH). We immunohistochemically investigated the HGF and c
      Met expression in 43 MFH tissue specimens. Furthermore, the correlation of the
      HGF and c-Met expression with tumor proliferative activity assessed by MIB-1
      indices was analyzed. Our results showed that positive cytoplasmic
      immunoreactivity for HGF and c-Met was identified in tumor cells in 36 (84%) and
      20 (47%) of the 43 MFH cases analyzed, respectively. Coexpression of HGF and c
      Met was observed in 20 (47%) of the 43 MFHs, and was correlated with high MIB-1
      proliferative indices (p = 0.0446). These findings strongly indicate that the
      HGF/c-Met signaling system plays an important role in promoting cell
      proliferation of human MFHs via an autocrine loop.

PMID- 15239349
TI  - Pathogenesis of early atherosclerotic lesions in infants.
AB  - High serologic lipid levels, infections, and genetic susceptibility have been
      proposed as possible etiologic factors of initial atherosclerotic lesions of the
      coronary arteries in infancy. At a recent WHO annual meeting, it was stated that
      breast milk substitutes cause irreparable damage in infants. This prompted us to
      verify whether formula feeding and parental cigarette smoking might play a role
      in the pathogenesis of early atherosclerotic alterations in infancy. The major
      epicardial coronary arteries from 36 infants dying suddenly and unexpectedly
      (sudden infant death syndrome) were embedded in paraffin and serially cut for
      histologic examination. In 67% of the cases, multifocal coronary early
      atherosclerotic lesions of varying entities were detected. The alterations ranged
      from focal plaques with mild myointimal thickening to juvenile soft plaques
      reducing the arterial lumen. A significant correlation was observed between the
      early atherosclerotic lesions and the risk factors considered. In particular, we
      noted different morphologic patterns related to formula feeding and cigarette
      smoking. Baby formula feeding and parental cigarette smoking might have an
      atherogenic effect on the coronary walls as from the first months of life. The
      lesions appear to be larger and more diffuse when both these atherogenic factors
      are present.

PMID- 15239350
TI  - Evolution of dilated cardiomyopathy (DCM) from idiopathic hypertrophic
      cardiomyopathy (IHCM) vs. inflammatory dilated cardiomyopathy (DCMi): a rare case
      of sudden death in an 8-year-old boy.
AB  - In rare cases, the diagnosis of hypertrophic and dilated cardiomyopathy (DCM) in
      children was established postmortem. Our case report deals with the sudden and
      unexpected death of an 8-year-old boy. The postmortem examination revealed non
      obstructive hypertrophy with irregular arrangement of muscular fibers, dilatation
      of the ventricles, endocardial fibrosis, microfocal vacuolization with enlarged
      hyperchromatic nuclei, and signs of inflammation with interstitial fibrosis. We
      present an evolution from idiopathic cardiomyopathy to DCM. To some extent, there
      were morphologic signs of an inflammatory process that first led us to suspect a
      specific inflammatory DCM.

PMID- 15239351
TI  - Extranodal Rosai-Dorfman disease. Clinical and pathological characteristics in a
      patient with a pseudotumor of bone.
AB  - We report the clinical and pathological findings of a 19-year-old Venezuelan
      patient with a proximal tibial lesion showing the histological and
      immunohistochemical characteristics of Rosai-Dorfman disease. The radiological
      studies showed a lithic bone lesion that was interpreted as a giant cell tumor.

PMID- 15239352
TI  - Another perspective.

PMID- 15239353
TI  - Arthroscopically assisted intra-articular corrective osteotomy of a malunion of
      the distal radius.

PMID- 15239354
TI  - Surgical evaluation and management of symptomatic lumbosacral meningeal cysts.
AB  - Sacral meningeal cysts are a fairly common finding in the workup of sciatica. In
      most instances, a cyst causes no symptoms. Occasionally, a symptomatic sacral
      cyst may present with chronic low back pain (radiculopathy), sensory loss in
      sacral dermatomes, perineal pain, or bowel or bladder dysfunction. Compared with
      computed tomography, magnetic resonance imaging shows meningeal cysts more often
      and allows better localization of sacral cysts. In this article, we present
      clinical guidelines that may be used to distinguish symptomatic cysts from
      asymptomatic cysts. We conclude that surgical treatment of a symptomatic cyst may
      include laminectomy with fenestration and imbrication of the cyst--or
      percutaneous treatment methods. Surgery for sacral meningeal cysts can lead to
      successful improvement of pain and function in activities of daily living in more
      than 80% of cases.

PMID- 15239355
TI  - Arthrodesis of the first metatarsophalangeal joint.
AB  - Arthrodesis has emerged as the primary salvage procedure for severe
      osteoarthritis of the first metatarsophalangeal (MTP) joint. Forty-three patients
      underwent arthrodesis of the first MTP joint with stabilization provided by
      either 2 crossed lag-screws or a dorsal plate and screws. First MTP joint
      arthrodesis was the primary procedure for 46 of the 54 treated feet. Joint
      surfaces were shaped into a ball-and-socket configuration to augment joint
      surface contact and facilitate alignment for arthrodesis. Postoperative care
      involved using a compressive bandage, a surgical shoe, and a cane, crutches, or a
      walker. Partial weight-bearing was allowed immediately after surgery. Few casts
      were used postoperatively. At a mean of 21.7 months (median, 13.5 months), 34 of
      the 43 patients completed a brief telephone survey about surgical outcomes.
      Radiographic measurements of intermetatarsal, hallux valgus, inclination, and
      dorsiflexion angles were made preoperatively and postoperatively. Mean time to
      fusion was 7.3 weeks; arthrodesis was successful for 50 of 52 feet (radiographs
      were missing for 2 of the 54 feet treated). Internal fixation devices were
      removed from 5 feet. Thirty (88.2%) of the 34 patients rated their result as
      excellent or good; the other 4 (11.8%) rated their result as poor.

PMID- 15239356
TI  - Functional outcome following anterior submuscular transposition of the ulnar
      nerve with V-Y lengthening of the flexor-pronator origin.
AB  - Functional outcome after V-Y musculofascial lengthening of the flexor-pronator
      musculotendinous origin was assessed in conjunction with submuscular
      transposition of the ulnar nerve for cubital tunnel syndrome. We retrospectively
      evaluated 38 submuscular transpositions with V-Y lengthening in 35 patients. A
      functional score was calculated on a 100-point scale both preoperatively and at
      latest follow-up, and pain and numbness scores were assessed using visual analog
      scales. Mean length of follow-up was 4.9 years (range, 2.5-7.9 years). Mean
      functional score improved from 33.5 preoperatively to 62.7 at latest follow-up
      (P<.001), pain improved from 7.4 to 3.5 (P<.001), and numbness improved from 7.0
      to 4.1 (P<.001). V-Y lengthening of the flexor-pronator origin is an effective
      alternative to musculofascial lengthening in combination with submuscular
      transposition for treatment of cubital tunnel syndrome.

PMID- 15239357
TI  - Stress fracture of the distal tibial physis following subtalar arthrodesis: a
      case report.

PMID- 15239358
TI  - Trapeziometacarpal instability and thenar muscle atrophy.

PMID- 15239359
TI  - Foot and ankle injuries in dance.
AB  - This review focuses on many of the foot and ankle injuries commonly seen among
      dancers. These unique athletes place extreme demands on their musculoskeletal
      system and thereby face a variety of acute and overuse injuries. Conservative
      treatment is successful in the majority of cases, but these patients often
      continue to dance while healing--commonly prolonging and at times complicating
      treatment. When surgery is being contemplated, the dancer's performance level and
      expectations about returning to dance after surgery should be thoroughly
      explored. Foot and ankle surgeries that routinely yield good to excellent results
      in the general population can prematurely end a dancer's otherwise promising
      career. The physician must consider all these factors when designing an
      appropriate treatment plan for a dancer.

PMID- 15239360
TI  - Cervical spine ankylosing spondylitis.

PMID- 15239361
TI  - Deaths associated with abortion compared to childbirth--a review of new and old
      data and the medical and legal implications.

PMID- 15239362
TI  - The reawakening of complementary and alternative medicine at the turn of the
      twenty-first century: filling the void in conventional biomedicine.

PMID- 15239363
TI  - Intellectual property reform for genetically modified crops: a legal imperative.

PMID- 15239364
TI  - The Health Insurance Portability and Accountability Act (HIPAA) implementation
      via case law.

PMID- 15239365
TI  - Discovery rule in medical malpractice under the Federal Tort Claims Act: the
      Supreme Court's decision in United States v. Kubrick was not meant to be
      secondary authority.

PMID- 15239366
TI  - Please, Sir, I want some more: Congress' carrot-and-stick approach to pediatric
      testing leaves therapeutic orphans needing more protection.

PMID- 15239367
TI  - The medical malpractice crisis--who will deliver the babies of today, the leaders
      of tomorrow?

PMID- 15239368
TI  - Internet drug sales: is it time to welcome "big brother" into your medicine
      cabinet?

PMID- 15239369
TI  - Factors affecting quality and postharvest properties of vegetables: integration
      of water relations and metabolism.
AB  - Growing of vegetables in the field, harvesting, handling in the packing house and
      storage are events in the lifetime of vegetables that are analysed from the point
      of view of the complex series of physiological transitions taking place in each
      of these events. Water is the major factor limiting plant metabolism and plants
      have developed fascinating mechanisms to cope with this limiting factor.
      Therefore, water relations (water, pressure and osmotic potential) are used as
      criteria for discussing plant stress physiology aspects such as osmotic, elastic
      adjustment and cold acclimation, as well as mechanical stress when the vegetable
      is harvested and during handling in the packing house. Consequences for the
      storage potential and quality of the vegetable are discussed. After harvesting,
      the postharvest cell has the ability to complete a complex series of
      physiological transitions that will influence vegetable quality andfurther
      processing operations. Metabolic changes in the cytosol, cell membrane and cell
      wall are described.

PMID- 15239370
TI  - Crocetin from saffron: an active component of an ancient spice.
AB  - The known properties of saffron (Crocus sativus, L.) and its components have been
      examined. Recently, hormone like effects in green algae and the anti-cancerogenic
      and anti-toxic effects, have been observed. In particular, the effects of
      crocetin, a carotenoids (8,8'-diapo-8,8'-carotenoic acid) present in saffron and
      characterized by a diterpenic and symmetrical structure with seven double bonds
      and four methyl groups, have been taken into consideration. It has been found
      that this compound enhances the oxygen diffusivity through liquids, such as
      plasma. As a consequence of this property, it has been observed that crocetin
      increases alveolar oxygen transport and enhances pulmonary oxygenation. It
      improves cerebral oxygenation in hemorrhaged rats and positively acts in the
      atherosclerosis and arthritis treatment. It inhibits skin tumor promotion in mice
      (i.e., with benzo(a)pyrene); it has an inhibitory effect on intracellular nucleic
      acid and protein synthesis in malignant cells, as well as on protein-kinase-C and
      prorooncogene in INNIH/3T3 cells. This is most likely due to its anti-oxidant
      activity. Furthermore, crocetin protects against oxidative damage in rat primary
      hepatocytes. It also suppresses aflatoxin B1-induced hepatotoxic lesions and has
      a modulatory effect on aflatoxin, B1 cytotoxicity, and DNA adduct formation on
      C3H10/T1/2 fibroblast cells. It also has a protective effect on the bladder
      toxicity, induced by cyclophosphamide. The experiments reported in the scientific
      literature and the interesting results obtained have been carried out in vitro or
      on laboratory animals, but not yet on man.

PMID- 15239372
TI  - Active food packaging technologies.
AB  - Active packaging technologies offer new opportunities for the food industry, in
      the preservation of foods. Important active packaging systems currently known to
      date, including oxygen scavengers, carbon dioxide emitters/absorbers, moisture
      absorbers, ethylene absorbers, ethanol emitters, flavor releasing/absorbing
      systems, time-temperature indicators, and antimicrobial containing films, are
      reviewed. The principle of operation of each active system is briefly explained.
      Recent technological advances in active packaging are discussed, and food related
      applications are presented. The effects of active packaging systems on food
      quality and safety are cited.

PMID- 15239371
TI  - Determination of aminoglycosides and quinolones in food using tandem mass
      spectrometry: a review.
AB  - The widespread use of antibiotics in dairy cattle management may result in the
      presence of antibiotic residues in food. While rapid screening tests are commonly
      used to detect the presence of antibiotics in food, more accurate chromatographic
      mass spectrometric methods combined with tandem mass spectrometry (MS/MS) are
      required to determine the identity and quantity of the antibiotic present. These
      methods (HPLC/MS/MS) may have the greatest potential for accomplishing direct
      multi-residue identifications in complex biological matrices, such as food. This
      study reviews recent applications of tandem mass spectrometry in the
      determination of antibiotic residues, such as aminoglycosides and quinolones in
      food.

PMID- 15239373
TI  - Review: HPLC determination of fumonisin mycotoxins.
AB  - An overview of liquid chromatographic methods, mainly employing fluorescence
      detection together with sample pre-treatment methods, is presented for the
      determination of the toxic group of fumonisin mycotoxins in various matrices.

PMID- 15239374
TI  - A medical legend: James L. Cunningham, M.D.

PMID- 15239375
TI  - West Virginia Coalition for Quality Health Care presents results of "GAP in the
      Mountains" project.

PMID- 15239376
TI  - Internal carotid artery flow arrest/reversal cerebral protection techniques.
AB  - We report on the progress of an ongoing prospective non-randomized trial
      evaluating carotid artery stenting (CAS) with adjuvant cerebral protection in
      patients who are considered high risk for surgery. The 62 patients (34M/28F) in
      this study underwent CAS with interruption or reversal of flow in the internal
      carotid artery to protect the brain from embolization of particulate debris that
      may otherwise egress to the brain resulting in a stroke. Twenty-seven patients
      (44%) had restenotic lesions after remote carotid endarterectomy and 11 (18%) had
      previous radical neck surgery with external beam radiation therapy for cancer.
      The average length of hospital stay was 1.3 +/- 0.7 days. There were no strokes
      or transient ischemic attacks during the procedure or follow-up. Intolerance to
      ICA flow arrest or reversal was noted in five patients, but the procedures were
      completed in stages without sequella. No significant change in NIH scale was
      reported based on independent neurology evaluation when baseline average scores
      (0.72 +/- 1.1) were compared to follow-up at 30 days (0.50 +/- .05) P > 0.05. The
      positive outcome in this small study suggests that CAS may be a safe alternative
      to CEA in high-risk patients.

PMID- 15239377
TI  - Thrombotic thrombocytopenic purpura following cardiovascular surgery: a case
      report.
AB  - Thrombotic thrombocytopenic purpura, a rare clinical syndrome characterized by
      thrombocytopenia and microangiopathic hemolytic anemia, was almost uniformly
      fatal until the introduction of plasma exchange in 1970. The thrombotic
      thrombocytopenic purpura following cardiovascular surgeries is relatively a new
      entity with high mortality if untreated. Plasma exchange is the most important
      therapy in this disease with good clinical outcomes. With the addition of this
      report, there are now 13 cases of thrombotic thrombocytopenic purpura in
      association with coronary artery bypass graft reported in the literature.

PMID- 15239378
TI  - The prevalence of obesity and elevated liver enzymes in children at a university
      gastroenterology clinic.
AB  - Obesity has been recognized as a risk factor for liver disease. We evaluated the
      prevalence of obesity and elevated liver transaminases in children referred to
      the Pediatric Gastroenterology Clinic at the Marshall University Joan C. Edwards
      School of Medicine in Huntington. In a retrospective chart analysis the following
      data were collected: demographic, anthropometric, Body Mass Index, liver enzymes,
      medications, and final diagnosis. Of the 2550 charts reviewed, 540 children (21%)
      were obese, 399 (16%) were overweight, and 1,611 (63%) had normal weight. Liver
      enzymes were recorded in 902 children (35%). Elevated enzymes were found in 79 of
      the children (8.7%), but only 31 were appropriate for final calculation. Elevated
      liver enzymes were significantly higher in obese children compared to overweight
      or normal weight children. Over 30% of our children were obese or overweight.
      Obesity is a risk factor for elevated liver enzymes and early assessment is
      recommended.

PMID- 15239379
TI  - Fibroepithelial polyp of the ureter presenting incidentally in a patient with a
      diverticular abscess.
AB  - We report on a patient with a fibroepithelial polyp of the distal ureter in whom
      the diagnosis was made incidentally while being examined for a diverticular
      abscess draining into the vagina. This patient's lack of symptoms and a possible
      relationship with the diverticular abscess is also explored.

PMID- 15239380
TI  - Alicyclobacillus spp. in the fruit juice industry: history, characteristics, and
      current isolation/detection procedures.
AB  - The first Alicyclobacillus spp. was isolated in 1982, and was originally thought
      to be strictly limited to thermophilic and acidic environments. Two years later,
      another Alicyclobacillus sp., A. acidoterrestris, was identified as the causative
      agent in spoilage of commercially pasteurized apple juice. Subsequent studies
      soon found that Alicyclobacillus spp. are soilborne bacteria, and do not strictly
      require thermophilic and acidic environments. Alicyclobacillus spp. posess
      several distinct characteristics; the major one is their ability to survive
      commercial pasteurization processes and produce off-flavors in fruit juices. The
      fruit juice industry has acknowledged Alicyclobacillus spp. as a major quality
      control target microorganism. Guaiacol and halophenols were identified as the
      offensive smelling agent in many Alicyclobacillus spp. related spoilage. Though
      the exact formation pathway of these off-flavors by Alicyclobacillus spp. are not
      yet identified, studies report that the presence of Alicyclobacillus spp. in the
      medium may be a major contributor to the formation of these off-flavors. Many
      identification methods and isolation media were developed in the last two
      decades. However, most of these methods were developed specifically for A.
      acidoterrestris, which was the first identified off-flavor producing
      Alicyclobacillus. However, recent studies indicate that other species of
      Alicyclobacillus may also produce guaiacol or the halophenols. In this respect,
      all Alicyclobacillus spp. should be monitored as potential spoilage bacteria in
      fruit juices. This article includes an overall review of the history of
      Alicyclobacillus spp., characteristics, suggested off-flavor production pathways,
      and commonly used identification methods for the currently identified
      Alicyclobacillus spp.

PMID- 15239382
TI  - Pullulan degrading enzymes of bacterial origin.
AB  - Pullulan degrading enzymes belong to a group of glycosylhydrolases that are
      widely distributed in nature and are produced by an extremely wide variety of
      species. Among them the thermophilic and mesophilic bacteria are a rich source of
      these enzymes. There are many biotechnological applications for these enzymes and
      a rapidly growing amount of information about their diversity, genetic as well as
      biochemical and biophysical characteristics. The properties of these enzymes vary
      and are somewhat linked to the natural environment inhabited by the producing
      organisms. Genes for these enzymes have been cloned from several strains and
      their amino acid sequences show highly conserved regions common to the enzymes of
      the amylase family. Molecular studies have greatly extended our knowledge on
      pullulan degrading enzymes and their biosynthesis. However, enzyme production
      levels have usually not been as high as had been assumed possible, and the
      properties of some enzymes are less than optimal for their industrial
      applications. Some of these problems can be overcome with the use of good
      producer organisms, optimized expression/secretion vectors, and site-directed
      mutagenesis. The molecular biology of pullulan degrading enzymes has been and
      continues to be a valuable system for studying basic questions of cell biology,
      such as mechanisms of gene regulation and secretion, and the structure-function
      relationships of proteins.

PMID- 15239381
TI  - Emerging chlamydial infections.
AB  - Chlamydiae are important intracellular bacterial pathogens of vertebrates. In the
      last years, novel members of this group have been discovered: Parachlamydia
      acanthamoebae and Simkania negevensis seems to be emerging respiratory human
      pathogens, while Waddlia chondrophila might be a new agent of bovine abortion.
      Various species have been showed to infect also the herpetofauna and fishes, and
      some novel chlamydiae are endosymbionts of arthropods. In addition, molecular
      studies evidenced a huge diversity of chlamydiae from both environmental and
      clinical samples, most of such a diversity could be formed by novel lineages of
      chlamydiae. Experimental studies showed that free-living amoebae may support
      multiplication of various chlamydiae, then could play an important role as
      reservoir/vector of chlamydial infections. Here we reviewed literature data
      concerning chlamydial infections, with a particular emphasis on the novely
      described chlamydial organisms.

PMID- 15239383
TI  - The phylogeny and signature sequences characteristics of Fibrobacteres, Chlorobi,
      and Bacteroidetes.
AB  - Fibrobacteres, Chlorobi, and Bacteroidetes (FCB group) comprise three main
      bacterial phyla recognized on the basis of 16S rRNA trees. Presently, there are
      no distinctive biochemical or molecular characteristics known that can
      distinguish these bacteria from other bacterial phyla. The relationship of these
      bacteria to other phyla is also not known. This review describes many signatures,
      consisting of defined and conserved inserts in widely distributed proteins, that
      provide distinctive molecular markers for these groups of bacteria. These
      signatures serve to clarify the evolutionary relationship between members of the
      FCB group, and to other bacterial phyla. A 4 aa insert in DNA Gyrase B (GyrB) and
      a 45 aa insert in the SecA proteins are uniquely shared by various Bacteroidetes
      species. The insert in GyrB is present in all Bacteroidetes species (>100)
      covering different orders and families, indicating that it is a distinctive
      characteristic of the group. Three signatures consisting of an 18 aa insert in
      ATPase alpha-subunit, an 8-9 aa insert in the FtsK protein and a 1 aa insert in
      the UvrB protein are commonly shared only by the Bacteroidetes and Chlorobi
      homologs providing evidence that these two groups are specifically related to
      each other. Two additional inserts in the RNA polymerase beta'-subunit (5-7 aa)
      and Serine hydroxymethyl-transferase (14-16 aa), which are commonly present in
      various Bacteroidetes, Chlorobi, and Fibrobacteres homologs, but not any other
      bacteria, provide evidence that these groups shared a common ancestor exclusive
      of all other bacteria. The FCB groups of bacteria are indicated to have diverged
      from this common ancestor in the following order: Fibrobacteres --> Chlorobi -->
      Bacteriodetes. The inferences from signature sequences are strongly supported by
      phylogenetic analyses. These observations suggest that the FCB groups of bacteria
      should be placed in a single phylum rather than three distinct phyla. Signature
      sequences in a number of other proteins provide evidence that the FCB group of
      bacteria diverged at a similar time as the Chlamydiae group, and that the
      Spirochetes and Aquificales groups are its closest relatives.

PMID- 15239384
TI  - Prolonged daycare-associated outbreak caused by Shigella sonnei--Delaware, July
      2002-April 2003.

PMID- 15239385
TI  - The social impact of medicine--chapter 20.
AB  - This paper, an overview of medical history, is based on a course I taught at the
      University of Delaware's Academy of Life Long Learning, "Medicine, the Old and
      the New." It will not be a chronology of medical events and discoveries, but a
      discussion of the social aspects of medicine, how medicine affected the everyday
      lives of people, from the religion-based medicine of antiquity to the super
      scientific medicine of today. This paper is a compilation of other historical
      papers including, but not limited to, those listed in the accompanying
      bibliography. It is not an original paper. This paper will consist of 25
      chapters. Dr. Peter V. Rocca, Editor-in-Chief of the Delaware Medical Journal
      (DMJ), is planning to publish one chapter in each successive issue of the DMJ.

PMID- 15239386
TI  - How many stars do you have?

PMID- 15239387
TI  - Time to gear up for HSAs.

PMID- 15239388
TI  - Chemically induced renal tubule tumors in the laboratory rat and mouse: review of
      the NCI/NTP database and categorization of renal carcinogens based on mechanistic
      information.
AB  - The incidence of renal tubule carcinogenesis in male and female rats or mice with
      69 chemicals from the 513 bioassays conducted to date by the NCI/NTP has been
      collated, the chemicals categorized, and the relationship between carcinogenesis
      and renal tubule hyperplasia and exacerbation of the spontaneous, age-related
      rodent disease chronic progressive nephropathy (CPN) examined. Where information
      on mechanism or mode of action exists, the chemicals have been categorized based
      on their ability to directly or indirectly interact with renal DNA, or on their
      activity via epigenetic pathways involving either direct or indirect cytotoxicity
      with regenerative hyperplasia, or exacerbation of CPN. Nine chemicals were
      identified as directly interacting with DNA, with six of these producing renal
      tubule tumors at high incidence in rats of both sexes, and in some cases also in
      mice. Ochratoxin A was the most potent compound in this group, producing a high
      tumor incidence at very low doses, often with metastasis. Three chemicals were
      discussed in the context of indirect DNA damage mediated by an oxidative free
      radical mechanism, one of these being from the NTP database. A third category
      included four chemicals that had the potential to cause DNA damage following
      conjugation with glutathione and subsequent enzymatic activation to a reactive
      species, usually a thiol-containing entity. Two chemicals were allocated into the
      category involving a direct cytotoxic action on the renal tubule followed by
      sustained compensatory cell proliferation, while nine were included in a group
      where the cell loss and sustained increase in renal tubule cell turnover were
      dependent on lysosomal accumulation of the male rat-specific protein, alpha2mu
      globulin. In a sixth category, morphologic evidence on two chemicals indicated
      that the renal tumors were a consequence of exacerbated CPN. For the remaining
      chemicals, there were no pertinent data enabling assignment to a mechanistic
      category. Accordingly, these chemicals, acting through an as yet unknown
      mechanism, were grouped as either being associated with an enhancement of CPN
      (category 7, 16 chemicals), or not associated with enhanced CPN (category 8, 4
      chemicals). A ninth category dealt with 11 chemicals that were regarded as
      producing increases in renal tubule tumors that did not reach statistical
      significance. A 10th category discussed 6 chemicals that induced renal tumors in
      mice but not in rats, plus 8 chemicals that produced a low incidence of renal
      tubule tumors in mice that did not reach statistical significance. As more
      mechanistic data are generated, some chemicals will inevitably be placed in
      different groups, particularly those from categories 7 and 8. A large number of
      chemicals in the series exacerbated CPN, but those in category 7 especially may
      be candidates for inclusion in category 6 when further information is gleaned
      from the relevant NTP studies. Also, new data on specific chemicals will probably
      expand category 5 as cytotoxicity and cell regeneration are identified as
      obligatory steps in renal carcinogenesis in more cases. Additional confirmatory
      outcomes arising from this review are that metastases from renal tubule tumors,
      while encountered with chemicals causing DNA damage, are rare with those acting
      through an epigenetic pathway, with the exception being fumonisin B1; that male
      rats and mice are generally more susceptible than female rats and mice to
      chemical induction of renal tubule tumors; and that a background of atypical
      tubule hyperplasia is a useful indicator reflecting a chemically associated renal
      tubule tumor response. With respect to renal tubule tumors and human risk
      assessment, chemicals in categories 1 and 2, and possibly 3, would currently be
      judged by linear default methods; chemicals in category 4 (and probably some in
      category 3) as exhibiting a threshold of activity warranting the benchmark
      approach; and those in categories 5 and 6 as representing mechanisms that have no
      relevance for extrapolation to humans.

PMID- 15239389
TI  - Environmental distribution, analysis, and toxicity of organometal(loid)
      compounds.
AB  - The biochemical modification of the metals and metalloids mercury, tin, arsenic,
      antimony, bismuth, selenium, and tellurium via formation of volatile metal
      hydrides and alkylated species (volatile and involatile) performs a fundamental
      role in determining the environmental processing of these elements. In most
      instances, the formation of such species increases the environmental mobility of
      the element, and can result in bioaccumulation in lipophilic environments. While
      inorganic forms of most of these compounds are well characterized (e.g., arsenic,
      mercury) and some of them exhibit low toxicity (e.g., tin, bismuth), the more
      lipid-soluble organometals can be highly toxic. Methylmercury poisoning (e.g.,
      Minamata disease) and tumor development in rats after exposure to dimethylarsinic
      acid or tributyltin oxide are just some examples. Data on the genotoxicity (and
      the neurotoxicity) as well as the mechanisms of cellular action of
      organometal(loid) compounds are, however, scarce. Many studies have shown that
      the production of such organometal(loid) species is possible and likely whenever
      anaerobic conditions (at least on a microscale) are combined with available
      metal(loid)s and methyl donors in the presence of suitable organisms. Such
      anaerobic conditions can exist within natural environments (e.g., wetlands, pond
      sediments) as well as within anthropogenic environmental systems (e.g., waste
      disposal sites and sewage treatments plants). Some methylation can also take
      place under aerobic conditions. This article gives an overview about the
      environmental distribution of organometal(loid) compounds and the potential
      hazardous effects on animal and human health. Genotoxic effects in vivo and in
      vitro in particular are discussed.

PMID- 15239390
TI  - Imatinib mesylate in the treatment of chronic myelogenous leukemia.
AB  - Imatinib mesylate binds to the inactive conformation of BCR-ABL tyrosine kinase,
      suppressing the Philadelphia chromosome-positive clone in chronic myelogenous
      leukemia (CML). Clinical studies of imatinib have yielded impressive results in
      the treatment of all phases of CML. With the higher rates of complete cytogenetic
      response with imatinib, molecular monitoring of disease has become mandatory in
      assessing response and determining prognosis. The practical aspects of the
      treatment of CML with imatinib are discussed. The emergence of imatinib
      resistance, albeit in a small percentage of patients, has prompted an evaluation
      of innovative treatment strategies.

PMID- 15239392
TI  - Imatinib mesylate in combination with other chemotherapeutic agents for chronic
      myelogenous leukemia.
AB  - Imatinib therapy is an important contribution to the management of patients with
      chronic myelogenous leukemia (CML). Despite high rates of hematologic and
      cytogenetic responses to imatinib therapy, the emergence of resistance to
      imatinib has been recognized as a major problem in the treatment of CML.
      Experimental and clinical studies suggest that imatinib as a single drug may not
      be sufficient to eradicate BCR-ABL-positive stem cells. Therefore, whether
      combinations of imatinib with other agents can increase the length of molecular
      remission and whether such combinations can prolong survival should be determined
      by large-scale clinical studies. In this review, we discuss efficacious
      combinations for future clinical trials. These regimens combine imatinib with
      conventional chemotherapeutic agents or with inhibitors of other signal
      transduction molecules that may be preferentially activated in CML cells.

PMID- 15239391
TI  - Biology of chronic myeloid leukemia and possible therapeutic approaches to
      imatinib-resistant disease.
AB  - Chronic myeloid leukemia (CML) is a stem cell disorder caused by a constitutively
      activated tyrosine kinase, the Bcr-Abl oncoprotein. An inhibitor of this tyrosine
      kinase, imatinib mesylate, is rapidly becoming the first-line therapy for CML.
      However, the development of resistance to this drug is a frequent setback,
      particularly in patients in advanced phases of the disease. Several mechanisms of
      resistance have been described, the most frequent of which are amplification
      and/or mutations of the BCR-ABL gene. To overcome resistance, several approaches
      have been studied in vitro and in vivo. They include dose escalation of imatinib,
      combination of imatinib with chemotherapeutic drugs, alternative Bcr-Abl
      inhibitors, inhibitors of kinases downstream of Bcr-Abl, farnesyl and
      geranylgeranyl transferase inhibitors, histone deacetylase, proteasome and cyclin
      dependent kinase inhibitors, arsenic trioxide, hypomethylating agents,
      troxacitabine, targeting Bcr-Abl messenger RNA, and immunomodulatory strategies.
      It is important to understand that these approaches differ in efficiency, which
      is often dependent on the mechanisms of resistance. Further investigations into
      the molecular mechanisms of disease and how to specifically target the abnormal
      processes will guide the design of new treatment modalities in future clinical
      trials.

PMID- 15239394
TI  - Porphyrias in Japan: compilation of all cases reported through 2002.
AB  - The first case of porphyria on record in Japan was a patient with congenital
      erythropoietic porphyria (CEP) reported by Sato and Takahashi in 1920. Since then
      until the end of December 2002, 827 cases of porphyrias have been diagnosed from
      characteristic clinical and/or laboratory findings (463 males, 358 females, and 6
      of unknown sex). Essentially all inherited porphyrias have been found in Japan,
      with the incidences and clinical symptoms generally being similar to those
      reported for other countries. The male-female ratio was approximately 1:1 for
      CEP, whereas it was higher for erythropoietic protoporphyria. In contrast,
      preponderances of female patients exist with acute hepatic porphyrias, such as
      acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary
      coproporphyria (HCP), and with undefined acute porphyria. Although porphyria
      cutanea tarda (PCT) is believed to be increasing recently in women in other
      countries because of smoking and the use of contraceptives, it is still by far
      more prominent in males in Japan than in females. The recent increasing
      contribution of hepatitis C virus infection to PCT in Japan has also been
      recognized. but there have been no PCT cases in Japan with HFE gene mutations.
      Familial occurrence and consanguinity were high for CEP, as expected; however,
      significant consanguinity was also noted in families where CEP, AIP, HCP, VP, or
      PCT occurred as a single isolated case without a family history of disease. This
      survey also revealed that as many as 71% of acute hepatic porphyria cases were
      initially diagnosed as nonporphyria and later revised or corrected to porphyria,
      indicating the difficulty of diagnosing porphyria in the absence of specific
      laboratory testing for porphyrins and their precursors in urine, stool, plasma,
      and erythrocyte samples.

PMID- 15239393
TI  - Imatinib therapy in clonal eosinophilic disorders, including systemic
      mastocytosis.
AB  - Primary (nonreactive) eosinophilia is operationally classified as either a
      "clonal" or an "idiopathic" process. Clonal eosinophilia stipulates the presence
      of cytogenetic, molecular, or bone marrow histologic evidence of acute leukemia
      or a chronic myeloid disorder. Idiopathic eosinophilia is a diagnosis of
      exclusion that is made after ruling out both "secondary" (reactive) and clonal
      eosinophilia. Hypereosinophilic syndrome is a subclass of idiopathic eosinophilia
      that requires the documentation of both sustained eosinophilia (> or =
      1500/microL for at least 6 months) and target-organ damage. A series of novel
      observations in the last 5 years have warranted a refined approach to the
      diagnosis as well as the treatment of clonal eosinophilic disorders, including
      systemic mastocytosis. At the center of these new developments are mutations
      involving the platelet-derived growth factor receptor genes (PDGFRA and PDGFRB),
      which have been pathogenetically linked to clonal eosinophilia, and their
      presence predicts complete as well as durable treatment responses to imatinib
      mesylate. The bone marrow histologic phenotype of these imatinib-sensitive
      eosinophilic disorders includes systemic mastocytosis, chronic eosinophilic
      leukemia, chronic myelomonocytic leukemia, and atypical chronic
      myeloproliferative disorder.

PMID- 15239395
TI  - Diverse clinical applications using advantages of allogeneic peripheral blood
      stem cell transplantation.
AB  - The diverse clinical applications of allogeneic peripheral blood stem cells based
      on use of their advantages are summarized. It is apparent that more stem cells
      and T-lymphocytes can be harvested by mobilization treatment with cytokines from
      healthy donors in allogeneic peripheral blood stem cell transplantation (PBSCT)
      than in bone marrow transplantation. It is also clear that a stronger graft
      versus-tumor effect can be induced with allogeneic PBSCT than with bone marrow
      transplantation. One merit of allogeneic PBSCT is that it allows clinicians to
      design diverse clinical applications. It would appear that allogeneic PBSCT may
      be preferable in special clinical settings, such as advanced hematological
      malignancies, situations requiring a strong graft-versus-tumor effect,
      nonmyeloablative stem cell transplantation, and situations requiring a megadose
      of stem cells. Cytokine-primed peripheral blood stem cells can also be used for
      adoptive immunotherapy, such as a nonprimed donor lymphocyte infusion.

PMID- 15239396
TI  - Extramedullary relapse confirmed by fluorescence in situ hybridization study of
      an ear mass in acute promyelocytic leukemia.
AB  - A 40-year-old man with acute promyelocytic leukemia (APL) achieved complete
      remission after induction chemotherapy combined with all-trans-retinoic acid. A
      mass developed in the left ear 24 months later. Relapse of APL was suspected at
      morphologic examination of the biopsy specimen of the ear mass, but t(15;17) and
      PML/RAR alpha rearrangement were not detected by chromosomal, fluorescence in
      situ hybridization (FISH), or reverse transcription polymerase chain reaction
      analysis of bone marrow samples. FISH performed on the ear mass revealed
      t(15;17). To our knowledge, this case is the first reported case of
      extramedullary relapse of APL confirmed by FISH study of a biopsy specimen of
      extramedullary tissue.

PMID- 15239397
TI  - Primary mediastinal large B-cell lymphoma: a single-institution clinical study in
      Japan.
AB  - Several clinicopathologic studies of primary mediastinal large B-cell lymphoma
      (Med-DLBCL) have been reported from Western countries; however, only a few series
      of at most 10 cases are available in Japan. To further clarify the Med-DLBCL
      occurring in Japan, we analyzed the clinical features of 28 patients with Med
      DLBCL diagnoses who were treated at the National Cancer Center Hospital between
      1982 and 2002. The median age was 37 years (range, 18-80 years). The ages of 16
      male patients ranged widely from 18 to 80 years, whereas the 12 female patients
      appeared to show a single age peak at 20 to 40 years. Only 13 patients (46%)
      achieved a complete response with initial treatments, mostly by CHOP-like
      regimens (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisolone)
      followed by radiotherapy. The estimated 3-year overall and failure-free survival
      rates were 32% and 33%, respectively, indicating the relatively unfavorable
      prognosis of the patients in our series. The following factors were found to be
      significantly associated with shortened survival prospects: age >60 years, serum
      lactate dehydrogenase level greater than normal, performance status >1, and
      presence of bulky mediastinal mass. In conclusion, the clinical features of
      Japanese patients with Med-DLBCL may be different from those with the disease in
      Western countries. Because this investigation was a single-institution study with
      a limited number of patients, however, multicenter confirmatory studies are
      needed.

PMID- 15239398
TI  - Sustained remissions with long-term weekly chlorambucil maintenance therapy in
      patients with mucosa-associated lymphoid tissue lymphoma.
AB  - Five patients with mucosa-associated lymphoid tissue (MALT) lymphoma
      (Helicobacter pylori negative) were initially treated with daily chlorambucil
      (Chl, 0.06-0.08 mg/kg per day) and achieved complete remission (n = 4) or partial
      remission (n = 1). They were then given long-term weekly Chl as maintenance
      therapy with good results. One patient came off treatment and has remained in
      continued remission for 44 months. This simple, low-cost, and convenient approach
      deserves further evaluation in patients with MALT lymphoma and other indolent and
      incurable lymphoproliferative disorders.

PMID- 15239399
TI  - Case of B-cell lymphoma with rearrangement of the BCL1, BCL2, BCL6, and c-MYC
      genes.
AB  - We managed a peculiar case of lymphoma showing immunohistochemical overexpression
      of cyclin D1. At initial examination the patient had meningeal lymphomatosis and
      general lymphadenopathy. Histologic examination of biopsy specimens of inguinal
      lymph nodes showed tumor cells and vague nodular growth resembling lymphoblasts.
      The results of flow cytometric analysis were positive for CD10, CD20, CD103, and
      immunoglobulin G (IgG) and Ig kappa and were negative for CD5, CD23, and terminal
      deoxynucleotidyl transferase activity. Results of immunohistochemical analysis of
      paraffin-embedded specimens were positive for cyclin D1 and Bcl2 in the tumor
      cells. Sixty percent of tumor cells had positive results for MIB1/Ki67.
      Cytogenetic and molecular studies revealed tumor cells simultaneously had
      t(14;18)(q32;q21), t(11;22)(q13;q11), t(8;14)(q24;q32), and t(3;14)(q27;q32) with
      the rearrangement of BCL1, BCL2, BCL6, and c-MYC genes. Lymphadenopathy showed a
      quick and complete response to doxorubicin-containing systemic chemotherapy with
      rituximab, but the central nervous system disease progressed and killed the
      patient.

PMID- 15239400
TI  - NK/T-cell lymphoma associated with Epstein-Barr virus in a patient infected with
      human immunodeficiency virus: an autopsy case.
AB  - Natural killer (NK)/T-cell lymphoma associated with Epstein-Barr virus (EBV) in a
      patient infected with human immunodeficiency virus (HIV) is very rare. The
      authors encountered a case of NK/T-cell lymphoma in a 36-year-old man who
      presented with an ulcerative mass on both tonsils. During assessment, HIV
      positivity was noted. The EBV was detected by EBV-encoded RNA 1 messenger RNA in
      situ hybridization and polymerase chain reaction for EBV-encoded nuclear antigen
      1. On immunohistochemical staining, the infiltrated lymphoid cells of the tonsils
      demonstrated positvity for CD3, CD56, UCHL1, and granzyme, a finding compatible
      with NK/T-cell lymphoma. The patient received radiation therapy and chemotherapy,
      but died as a result of opportunistic infection of invasive aspergillosis after
      tumor recurrence. An autopsy was done with the consent of the patient's family.
      To our knowledge, this is the first case in an HIV patient of NK/T-cell lymphoma
      of the tonsils associated with EBV, confirmed by autopsy. NK/T-cell lymphoma
      should be considered in the HIV-positive patients with an ulcerating tonsillar
      mass.

PMID- 15239401
TI  - Fulminant hemophagocytic syndrome with a high interferon gamma level diagnosed as
      macrophage activation syndrome.
AB  - A 26-year-old woman presented with general fatigue, persistent fever, nuchal
      lymphadenitis, thrombocytopenia, and liver damage. From the bone marrow finding,
      we diagnosed her condition as hemophagocytic syndrome. Steroid pulse therapy,
      cyclosporin A treatment, and combined chemotherapy generated no response. The
      patient showed severe mucosal bleeding, rapidly experienced multiple organ
      failure, and finally died of a brain hemorrhage on the 13th hospital day. Epstein
      Barr virus, cytomegalovirus, human herpes virus type 6, human parvovirus B19, and
      herpes simplex virus were not detected. Autopsied samples of the spleen, bone
      marrow, and liver showed extreme proliferation of activated macrophages, so
      called histiocytes, without lymphoid malignancy. The interferon gamma level at
      presentation was prominently high. The continuously elevated levels of ferritin
      and soluble interleukin 2 receptor were correlated with the catastrophic outcome.
      The disease in our case mimicked infantile hemophagocytic lymphohistiocytosis.
      However, there was neither a family history of the disease nor a mutation in the
      perforin gene. So, it is reasonable to categorize our case as macrophage
      activation syndrome. Although our patient lacked arthritis or eruption, we cannot
      deny the possibility that an oligoarthritis type of systemic-onset juvenile
      rheumatoid arthritis or, considering the patient's age, adult-onset Still disease
      lies at the base of our case.

PMID- 15239402
TI  - Hematopoietic progenitor cells residing in muscle engraft into bone marrow
      following transplantation.
AB  - Hematopoietic and mesenchymal stem cells can potentially be the same cell type or
      adhere simultaneously in both bone marrow (BM) and muscle. In this study, we
      asked whether murine BM-derived cells could be tracked in muscle tissue after BM
      transplantation and whether muscle-derived cells have hematopoietic potential. To
      answer the first question, we transplanted BM from male BALB/c mice into
      irradiated female recipients and analyzed for engraftment. We used quantitative
      polymerase chain reaction (PCR) and fluorescent in situ hybridization techniques
      for Y chromosome-specific gene probes. A high number of BM-derived cells were
      located in both the intravascular and extravascular spaces in muscle tissue after
      BM transplantation. To answer the second question, we analyzed colony-forming
      potential in vitro with soft-agar assays and the competitive engraftment
      potential in vivo of muscle-derived cells. Engraftment levels of male cell
      populations were tested by quantitative PCR. The long-term engraftment potential
      of muscle-derived cells was low compared with that of BM. We conclude that there
      is intensive cellular trafficking between BM and muscle tissue. The engraftment
      potential of muscle-derived stem cells into BM is low and corresponds to the low
      amounts of hematopoietic colony-forming cells found in muscle tissue.

PMID- 15239403
TI  - Impact of cytogenetics on outcome of stem cell transplantation for acute myeloid
      leukemia in first remission: a large-scale retrospective analysis of data from
      the Japan Society for Hematopoietic Cell Transplantation.
AB  - On the basis of transplantation data from the Japan Society for Hematopoietic
      Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at
      diagnosis on the outcome of transplantation in 628 patients with acute myeloid
      leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or
      allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete
      remission. For autologous SCT, patients at good cytogenetic risk had a
      significantly lower relapse rate (P = .017) and a significantly higher event-free
      survival (EFS) (P = .013) compared with those at intermediate risk. For
      allogeneic SCT, patients at good cytogenetic risk had a significantly lower
      relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at
      poor risk. For unrelated SCT, there was no significant difference in relapse rate
      or EFS between patients at good risk and those at intermediate risk. Comparison
      of the 3 transplantation modalities revealed that autologous SCT patients had a
      significantly higher incidence of relapse compared with related or unrelated SCT
      patients in the intermediate-risk group but not in the good-risk group. However,
      there were no significant differences in EFS among the 3 transplant modalities in
      either of these 2 risk groups. In multivariate analysis, cytogenetics was found
      to be an independent predictor of relapse as well as of treatment failure.

PMID- 15239404
TI  - Chronic graft-versus-host disease of the liver presenting as an acute hepatitis
      following nonmyeloablative hematopoietic stem cell transplantation.
AB  - Chronic graft-versus-host disease (GVHD) of the liver usually presents as an
      indolent cholestatic disease. We observed 3 patients in whom chronic GVHD of the
      liver after allogeneic nonmyeloablative hematopoietic stem cell transplantation
      (HSCT) presented with marked elevations of serum aminotransferases, clinically
      resembling acute viral hepatitis. The liver biopsies revealed predominant diffuse
      lobular injury and degenerative small bile ducts. Prompt administration of high
      dose immunosuppressive therapy achieved a rapid improvement of liver enzymes and
      bilirubin levels. We conclude that a distinct syndrome of chronic hepatic GVHD
      presenting as an acute hepatitis should be considered as one possible explanation
      for hepatic dysfunction in patients who receive nonmyeloablative allogeneic HSCT.

PMID- 15239405
TI  - May-Hegglin anomaly developing myelodysplasia and acute myeloid leukemia.

PMID- 15239406
TI  - A Medicare drug law has Rorschach Test features.

PMID- 15239407
TI  - Empirically mapping the subspecialties of cardiovascular-interventional
      technology.
AB  - As the practice of cardiovascular interventional technology (CVIT) has evolved
      over the last 50 years, so has the role of radiographers employed in this
      specialty. In 1991, the American Registry of Radiologic Technologists (ARRT)
      initiated a certification program to recognize radiologic technologists
      practicing in CVIT. The certification program consisted of a single examination
      that covered all aspects of CVIT (e.g., neurologic, cardiac, genitourinary). In
      2000, the ARRT conducted a study to investigate further the nature of
      subspecialization occurring within CVIT. A comprehensive job analysis
      questionnaire was developed that consisted of 137 clinical activities organized
      into 19 general domains of practice. The questionnaire was completed by a
      national sample of 848 radiologic technologists working in CVIT, who indicated
      the frequency with which they performed each of the 137 activities. Responses
      were subjected to cluster analysis to classify technologists into homogeneous
      groups corresponding to different CVIT subspecialties. Results indicated that
      CVIT consists of two major subspecialties: one corresponding to cardiac
      procedures and one corresponding to procedures involving organ systems other than
      the heart. Other smaller subspecialties also emerged from the cluster analysis. A
      multidimensional scaling of the profiles suggested that CVIT subspecialization
      can be explained by two dimensions: (1) whether the procedures are diagnostic or
      interventional and (2) the type of organ system involved. The findings are
      discussed in terms of their implications for education, certification, and
      performance evaluation.

PMID- 15239408
TI  - The process of outcome assessment in a school of allied health sciences.
AB  - This article describes a process of outcome assessment for a school of allied
      health sciences to assist others who may be involved in a similar endeavor. In
      the mid-1990s, the Indiana University Purdue University Indianapolis (IUPUI)
      Office of Planning and Institutional Improvement charged each of the schools on
      its campus with developing a process to determine how and to what degree students
      were meeting the IUPUI Principles of Undergraduate Education; the focus was on
      student learning. The administration and faculty of the School of Allied Health
      Sciences decided to expand the assessment from student learning to include
      assessment of the school's five goal statements, which were part of its mission.
      After several years of work, faculty in the school developed a plan of assessment
      including competencies, strategies, measurements, and desired outcomes. In 2001,
      the outcomes themselves were assessed, and actions were taken; reassessment
      occurred in 2002.

PMID- 15239409
TI  - Approaches to leadership development used by deans of allied health.
AB  - Deans and directors of allied health units in member institutions of the
      Association of Schools of Allied Health Professions (ASAHP) were surveyed to
      determine their approaches to leadership development. Of 99 deans and directors
      surveyed, 75 (76%) responded. All respondents had held at least one academic
      administrative position before their current position; assistant or associate
      dean were the most common positions. The respondents' leadership development
      included participation in service to the ASAHP or another health or allied health
      association. More female respondents (67%) than male respondents (47%) reported
      being mentored. Most frequently listed programs, workshops, and activities for
      leadership development were Harvard University's Management Development Program,
      regional allied health deans groups, and institutional leadership programs. Of
      respondents, 60% viewed professional experience as being more beneficial in
      leadership development than formal programs, workshops, and activities. The most
      important skills directly developed from such activities were strategic planning
      and forecasting, having a vision, and team or collaboration building.

PMID- 15239410
TI  - Effects of interprofessional rural training on students' perceptions of
      interprofessional health care services.
AB  - Interprofessional training has been advocated in the education of students in
      health care professions to facilitate collaboration and cooperation among health
      care providers. This study reported on one facet of the outcomes of a larger
      grant project funded by the Department of Health and Human Services HRSA grant #1
      D36 AH 10082-03, which aimed to develop a new and innovative model for
      interprofessional student training. Over the 3-year period of the project, a
      total of 111 students from allied health professions including occupational
      therapy, physical therapy, and pharmacy participated in the project training.
      Participants' perceptions on interprofessional service were assessed before and
      after they participated in the project by the Interprofessional Education
      Perception Scale. Results of a univariate repeated measures two-way analysis of
      variance revealed a significant increase in participants' positive perceptions
      regarding interprofessional practice after they participated in the project (p <
      0.05), and the significant increases were independent of the duration of the
      training (p < 0.01 for short-term and long-term training). A significant
      interaction between the duration of the training and pretest and posttest scores
      of the participants was found (p < 0.05) and students who participated in long
      term training reported more positive attitudes on the posttest. These encouraging
      findings are supported and strengthened further by the qualitative data of the
      study, suggesting the training project has a significant impact on allied health
      students' perceptual attitudes toward interprofessional service delivery.
      Findings of the study are discussed related to the improvement of quality care
      and to the recruitment and retentions of health care providers in rural and
      underserved areas.

PMID- 15239411
TI  - Integrating research into the culture of allied health professions: the
      background and a review of issues in the United Kingdom.
AB  - This article reviews the challenges and barriers to change associated with
      development of a research culture in allied health professions within the higher
      education sector. We address the cultural upheaval and alterations in ways of
      working experienced by higher education and the health professions in recent
      times as a result of government policy as it applies to education and the
      National Health Service in the United Kingdom. Cooperation between higher
      education and the National Health Service in developing a culture of research in
      the health professions is fundamental to achieving evidence-based practice in
      health care. Improving research capability is hampered, however, by lack of
      funding and institutional barriers to change and barriers within individuals.
      Engendering a sense of identity and ownership in relation to change and a
      strategic approach to the next Research Assessment Exercise are essential if
      allied health professional programs are to survive within higher education.

PMID- 15239412
TI  - European health policy: working within a paradox.
AB  - This article gives an overview of the position of European health policy within
      the European Union. A general introduction as to what the European Union is, its
      structure, and its purposes is followed by an explanation of the status of an
      overriding European health policy. What is revealed through the debate is the
      situation in which potential conflict between member states and the European
      Commission has suppressed the establishment of an integrated health policy. The
      debate also reveals a paradox, however, because other drivers and policy
      decisions are creating health policy in a partly unofficial and nonintegrated
      way.

PMID- 15239413
TI  - Genetics internet resources for allied health professionals.
AB  - As the field of genetics continues to grow at a rapid rate, so does the
      application to patient care delivered by allied health professionals. At the same
      time, it has been shown that allied health professionals often lack confidence in
      their knowledge of genetics as a result of limited education about genetics. The
      current study was an interdisciplinary effort devised to explore Internet
      resources for learning about human genetics as they apply to the allied health
      professions. A rating scale was developed to assess the format and the content of
      the websites and to assess other websites that may be identified in the future.
      Four of the seven websites that received the highest mean ratings are discussed
      in more detail. Two of the websites address basic concepts in genetics, and the
      other two provide resources for current topics and research in genetics as it
      pertains to patient care.

PMID- 15239414
TI  - Health literacy: universal precautions needed.
AB  - Inadequate health literacy adversely affects health care outcomes and the quality
      of life of 90 million Americans and costs the health care system dollars 73
      billion annually. Current strategies addressing inadequate health literacy
      primarily target physicians, nurses, and pharmacists but omit the allied health
      practitioners responsible for providing most patient services. The 2003 Coalition
      for Allied Health Leadership Health Literacy Project team undertook a survey of
      allied health professionals and educators to assess their awareness and needs
      concerning inadequate health literacy. Less than one third of all respondents
      were aware of the issues surrounding health literacy or that health literacy
      resources are available or had institutional policy or goals to address health
      literacy. Brochures and videos were identified most frequently as new resources
      needed to establish or increase the effectiveness of health literacy awareness
      programs. The results of this project indicated that there is substantial
      opportunity to increase awareness of the impact of health literacy, to develop
      and assess institutional policies toward health literacy, and to create new
      resources to promote health literacy within the allied health professions. Any
      approach to improving health literacy must be universal by involving all health
      care professionals and all patients in the intervention.

PMID- 15239415
TI  - Pairing of opposite learning styles among allied health students: effects on
      collaborative performance.
AB  - To understand better determinants of effective collaboration in allied health
      education, students were paired by similar and opposite learning styles to work
      on a simulated clinical case exercise. Fifty-six sophomore and junior students
      enrolled in an anatomy, physiology, and pathophysiology course from a variety of
      allied health programs were assigned randomly in pairs to one of three subsets
      based on their Kolb Learning Style Inventory scores (concrete versus abstract
      learners). The students read the history and physical examination findings of an
      immunocompromised patient with an abscess in an undisclosed spinal cord location,
      then answered a series of case questions. Analysis of variance revealed that
      mismatched pairs (concrete/abstract) performed significantly better than matched
      concrete pairs (F2,21 = 3.83, p < 0.05) and slightly better than matched abstract
      pairs. This higher performance of the mismatched group was not attributed to
      differences in either general or specific level of academic preparation among the
      groups, as measured by cumulative grade point average and prior course
      examination scores, respectively (F2,21 = 2.15, p > 0.05 and F2,21 = 3.04, p >
      0.05). Collapsing of all three subset groups into one cohort revealed that case
      exercise performance was correlated moderately, however, to cumulative grade
      point average (r = 0.49, p < 0.01) and correlated strongly to prior course exam
      scores (r = 0.76, p < 0.001). These findings suggest that clinical collaboration
      skills are enhanced not only by individual level of academic preparation but also
      by intentional pairing of concrete with abstract learners.

PMID- 15239416
TI  - To believe or not to believe: looking into the unbelievable.

PMID- 15239417
TI  - Therapeutic impact of abdominopelvic computed tomography in patients with acute
      abdominal symptoms.
AB  - PURPOSE: To determine the diagnostic and therapeutic impact of abdominopelvic
      computed tomography (CT) in patients with acute abdominopelvic pain. MATERIAL AND
      METHODS: Referring clinicians completed pre-CT and post-CT questionnaires for 50
      patients in whom CT had been requested because of acute abdominopelvic pain.
      Clinicians recorded their leading diagnosis, confidence in this, and intended
      management. Following CT, clinicians again recorded these responses in the light
      of CT findings. Responses pre-CT and post-CT were compared in order to determine
      diagnostic and therapeutic impact. RESULTS: Diagnostic confidence rose
      significantly following CT (mean score 6.8 pre-CT versus 8.3 post-CT; P<0.0001).
      Intended management changed because of CT findings in 29 (58%) patients: 14 (28%)
      subjects whose intended management was surgical were treated medically and an
      additional 2 were transferred to gynecological care; 4 patients whose intended
      management was medical were treated surgically; 2 patients whose intended
      management was medical were treated by percutaneous drainage; a patient whose
      intended management was percutaneous drainage was treated by surgery. Of 6
      patients with uncertain management pre-CT, 2 were treated surgically and 4
      medically. The leading diagnosis also changed as a consequence of CT in 7 (33%)
      of 21 patients in whom intended management did not alter. CONCLUSION: CT in
      patients with acute abdominopelvic pain has considerable diagnostic and
      therapeutic impact, altering management in 58% of patients studied. The major
      effect is to avert intended laparotomy.

PMID- 15239418
TI  - Unusual migration in abdomen of a wire for surgical localization of breast
      lesions.
AB  - We report a case of migration of a surgical localization wire from the breast to
      the abdomen. A 41-year-old female underwent presurgical needle localization of a
      deep-sited left-sided breast lesion. Migration of the localization wire in the
      chest wall occurred during the procedure documented by imaging. Computed
      tomography (CT) examination showed no evidence of the wire in the left lower lung
      field, no peritoneal free fluid, active bleeding, or abnormalities of abdominal
      organ, but a metallic-density representing the localization wire was seen for a
      length of 13 cm from the right diaphragmatic crus to the right psoas muscle,
      close to the inferior vena cava. A following CT examination showed the wire
      partially outside the inferior vena cava and partially inside the right iliac
      vein. The wire was successfully taken out by an angiographic interventional
      procedure.

PMID- 15239419
TI  - Cerebral CT and MRI findings in cervicocephalic artery dissection.
AB  - PURPOSE: To explore the frequency and patterns of brain infarction and other
      brain manifestations in cervicocephalic artery dissection (CCAD) and to evaluate
      the correlation between vessel wall findings and infarctions. MATERIAL AND
      METHODS: The medical records and films of 136 consecutive CCAD patients diagnosed
      in Oulu University Hospital during the 20-year period since 1982 were reviewed.
      Five patients with no brain imaging were excluded. RESULTS: One-hundred-and
      twenty-seven patients underwent cerebral CT and four patients MRI. Brain
      infarction was detected in 73 patients (56%), 43 of whom had cerebral infarction
      associated with anterior circulation dissection and 30 cerebellar infarction
      associated with posterior circulation dissection. Occlusion of the dissected
      vessel was accompanied by infarction in 76%, irregular stenosis in 40%, and other
      findings in 12%. Of the anterior circulation infarctions, territorial and
      subcortical infarctions and territorial infarctions with fragmentation, which are
      considered embolic, accounted for 95%, while only 5% were in the watershed area
      and considered hemodynamic. Intracranial posterior circulation dissection rarely
      caused infarction (in 1/11 of the dissected vessels), whereas intracranial
      anterior circulation dissection resulted in infarction more commonly (9/12).
      Altogether 23% of patients with intracranial CCAD had subarachnoid hemorrhage.
      Hemorrhagic transformation was present in five patients. CONCLUSIONS: More than
      half of CCAD patients have cerebral or cerebellar infarction at CT or
      conventional MR imaging. Occlusion of the dissected vessel is accompanied by
      infarction more often than other vessel wall abnormalities. Most cerebral
      infarctions caused by arterial dissections are of embolic origin. Intracranial
      dissections cause subarachnoid hemorrhage in more than 20% of patients.

PMID- 15239420
TI  - An unusual cause of mediastinal widening: bilateral innominate vein aneurysms.
AB  - We present a case of aneurysm of bilateral innominate veins and vena cava
      superior. Chest X-ray, computed tomography, and 3D contrast enhanced magnetic
      resonance angiography findings are described. The etiology of venous aneurysms is
      reviewed and clinical management options are discussed.

PMID- 15239421
TI  - Systemic-to-pulmonary venous shunt in superior vena cava obstruction: depiction
      on computed tomography venography.
AB  - PURPOSE: To describe computed tomography (CT) venographic appearances of systemic
      to-pulmonary venous shunts with CT venography and three-dimensional
      reconstruction images from patients with superior vena cava obstruction. MATERIAL
      AND METHODS: From January 1994 to April 2002, CT venography was performed in 45
      patients with superior vena cava obstruction using a single-detector helical CT
      scanner (n=38) and four-detector row CT scanner (n=7). Analysis of CT scan data
      included the cause and degree of venous obstruction, the presence of pleural
      thickening and enhancement, and the attenuation of pulmonary veins. The causative
      factor for systemic-to-pulmonary venous shunt was evaluated using the Fisher
      exact test. RESULTS: Systemic-to-pulmonary venous shunts were observed in four
      patients (9%) who had high-attenuated pulmonary veins and pleural enhancement on
      CT venography. Pleural thickening (P=0.01) and a history of pulmonary
      tuberculosis (P=0.034) are statistically significant risk factors. CONCLUSION: CT
      venography showed strong pleural enhancement and high-attenuated pulmonary veins
      indicating systemic-to-pulmonary venous shunts. Radiologists should study the
      earlier enhancement of pulmonary veins in patients with superior vena cava
      obstruction.

PMID- 15239422
TI  - Long-term results after endovascular repair of abdominal aortic aneurysms with
      the Stentor and Vanguard stent-graft.
AB  - PURPOSE: To present a single institution experience of long-term results after
      endovascular repair of abdominal aortic aneurysms (AAA) with the Stentor and
      Vanguard stent-grafts. MATERIAL AND METHODS: Twenty-three patients (20 men, 3
      women; mean age 68 years, range 53-81 years) were included in this prospective
      study. A first generation nitinol stent-graft (Stentor) was used in 12 patients
      and a second generation (Vanguard) in 11 patients. Follow-up was performed with
      magnetic resonance imaging (MRI) with contrast-enhanced MR angiography (CE MRA)
      at 1, 6, and 12 months, and thereafter annually (median follow-up 3 years; range
      8 months to 8 years). A conventional radiograph of the abdomen was also
      performed. Before secondary intervention the findings on MRI with CE MRA were
      confirmed with spiral computed tomography (CT) and/or angiography (DSA). RESULTS:
      Only one patient (4%) had no complication. Endoleak was found in 15 patients
      (65%), graft migration in 8 (35%), and graft deformation in 18 (78%). Secondary
      endovascular repair was required in 7 patients (30%) and 7 (30%) were converted
      to open repair. CONCLUSION: Complications with the Stentor and Vanguard stent
      grafts were common. Long-term follow-up of endovascularly repaired AAA is
      mandatory.

PMID- 15239423
TI  - Computed tomography-guided pulmonary nodule localization before thoracoscopic
      resection.
AB  - PURPOSE: To assess the success rate and complication rate of a CT-guided
      pulmonary nodule-marker system before thoracoscopic resection. MATERIAL AND
      METHODS: In 24 patients (15 M, 9 F; age range, 18-71 years) a total of 25
      pulmonary nodules (in 1 patient 2 lesions simultaneously) were marked with a
      special wire under CT-guidance and then thoracoscopically resected. We evaluated
      lesion size, lesion distance to the pleura, the time of intervention,
      complications, and thoracoscopic success rate. RESULTS: Mean lesion size was 7 mm
      (range 4-15 mm) and mean lesional distance to the pleura was 13 mm (range 2-31
      mm). The pulmonary nodule-marker system was positioned successfully in all 25
      pulmonary nodules within 5-11 min (mean 7.5 min). Minimal pneumothoraces were
      observed in five patients with no requirements of chest drains. In addition, no
      bleeding complications or hematothorax were observed. All 25 pulmonary nodules
      could be resected thoracoscopically. However, in one patient (4%), the guide-wire
      dislocated during thoracoscopy, but the lesion could be successfully resected
      during thoracoscopy. CONCLUSION: The CT-guided placement of the pulmonary nodule
      marker system used here offers a safe and accurate guide for the localization of
      small pulmonary nodules during thoracoscopic resection.

PMID- 15239424
TI  - Pleuropulmonary blastoma in the area of a previously diagnosed congenital lung
      cyst: report of two cases.
AB  - Pleuropulmonary blastoma (PPB) is a rare primary malignant pulmonary tumor in
      pediatric patients. We report the development of PPB in the area of a previous
      pulmonary cyst in two children, one boy and one girl 5 and 12 years old,
      respectively. We present the clinical and radiological findings. A short review
      of the literature is included.

PMID- 15239425
TI  - Role of radiology in occupational medicine.
AB  - This review discusses the contribution of radiology to occupational medicine as
      well as work-related problems in radiology departments. Research issues are
      emphasized. Radiology has been used especially when diagnosing occupational
      respiratory and locomotive system problems and solvent-induced encephalo- and
      hepatopathy. The aim of research in these areas is usually to characterize
      occupational diseases and to identify physico-chemical hazards in the work place
      by comparing between groups of workers and non-exposed controls. Radiological
      imaging allows an objective characterization of the disease, and it may clarify
      the pathogenesis of the process and provide a useful epidemiological tool.
      Advanced statistical methods are often needed to adjust analyses for confounding
      variables. As the diagnostic requirements are increasing, more sensitive and
      sophisticated radiological methods, such as high-resolution computed tomography,
      magnetic resonance imaging and magnetic resonance spectroscopy, may be required
      for the early recognition of occupational health risks. This necessitates good
      cooperation between occupational health units and well-equipped imaging
      departments. Considering occupational problems in radiology departments, the
      increasing use of digital radiology requires ergonomic measures to control and
      prevent locomotive problems caused by work with computers. Radiation protection
      measures are still worth concern, especially in interventional radiology.

PMID- 15239426
TI  - Dose reduction in computed tomography by individualized scan protocols.
AB  - PURPOSE: To find a method of adjusting the mAs-value in relation to the size of
      the patient undergoing computed tomography (CT) examination as a means of
      minimizing the radiation dose to the patient. MATERIAL AND METHODS: A correction
      factor to be applied on the tube charge for each patient was calculated using two
      mathematical methods. This approach was tested on 4 Perspex phantoms of different
      sizes and geometries. Noise was measured in the images with and without use of
      the correction factors. Retrospectively, correction factors were calculated for
      12 CT examinations of the abdomen and the dose reduction was estimated for these
      patient studies. RESULTS: The variations in noise measured in the images of the
      different phantoms were dramatically reduced by both methods. The retrospectively
      performed patient study showed that the largest correction factor was 7 times
      greater than the smallest, which means that a dose reduction factor of 7 is
      possible in the extreme case. CONCLUSION: Our proposed methods of adjusting the
      applied tube charge (mAs-value) in relation to the size of the patient can be
      used on the vast majority of CT systems. The potential for dose reduction is
      great, especially for small patients.

PMID- 15239427
TI  - Multicenter evaluation of a new laser guidance system for computed tomography
      intervention.
AB  - PURPOSE: To measure the accuracy of laser-guided punctures and to evaluate the
      usefulness of the developed laser-guided system. MATERIAL AND METHODS: The study
      included 67 patients referred for computed-tomography-guided puncture. The
      majority of the punctured lesions were located in the chest (28 patients) or
      abdomen (19 patients). The mean diameter of the lesion was 3.1 cm, and the mean
      path length was 6.8 cm. The laser guide was movable along a horizontal or
      vertical rail and not physically connected to the CT unit. The angle of insertion
      was entered manually into the display of the unit by the interventional
      radiologist. A prospective multicenter trial was carried out. RESULTS: A mean of
      1.1 needle passes were necessary to reach the target, and in 55 (84.6%) of the
      patients the target was reached on the first needle pass. The mean deviation of
      the needle from the preselected angle was 1.8 degrees. The mean targeting time
      (from the initial localizing scan until the needle was in the target) was 15.6
      min. In every case, both the usefulness and the ease of use of the laser guidance
      system were subjectively evaluated on a 5-point scale; the mean usefulness score
      was 4.5, while the mean ease of use score was 4.7. CONCLUSION: Different users at
      four different centers found the laser guidance system useful and easy to use. A
      high level of accuracy of the puncture angle was obtained in most cases.

PMID- 15239428
TI  - Role of skeletal scintigraphy in advanced retinoblastomas.
AB  - PURPOSE: To document the incidence of skeletal metastases exclusively in advanced
      cases of retinoblastoma and to rationalize the use of preoperative skeletal
      scintigraphy in such patients. MATERIAL AND METHODS: Preoperative bone scans of
      36 consecutive patients with advanced retinoblastoma who underwent skeletal
      scintigraphy during 1998 to 2003 were analyzed retrospectively. Bone scans were
      classified as: Grade 1 (high probability scan for skeletal metastases), Grade 2
      (equivocal malignant or benign abnormalities), or Grade 3 (normal or certainly
      benign lesions). RESULTS: Grade 1 scan was found in 3 (8.33%) patients; bone
      metastases were confirmed by additional investigations. Grade 2 scan was found in
      5 (13.88%) patients; bone metastases were excluded in all by additional
      investigations. Grade 3 scan was found in the remaining 28 (77.77%) patients.
      Extraorbital extension of disease was demonstrated by fine needle aspiration of
      lymph nodes in five patients, which included all three patients with Grade 1
      scan. In addition to lymph node metastases, two patients had intracranial
      extension of the disease; demonstrated by contrast-enhanced magnetic resonance
      imaging of the head. One patient had liver metastases detected on abdominal
      ultrasound. None of the patients had skeletal metastases only. CONCLUSION:
      Routine preoperative bone scan is not justified in patients with locally advanced
      retinoblastoma. Bone scan should only be performed in patients with documented
      extraocular metastatic disease.

PMID- 15239429
TI  - Bone stress injuries.
AB  - Bone stress injuries are due to cyclical overuse of the bone. They are relatively
      common in athletes and military recruits but also among otherwise healthy people
      who have recently started new or intensive physical activity. Diagnosis of bone
      stress injuries is based on the patient's history of increased physical activity
      and on imaging findings. The general symptom of a bone stress injury is stress
      related pain. Bone stress injuries are difficult to diagnose based only on a
      clinical examination because the clinical symptoms may vary depending on the
      phase of the pathophysiological spectrum in the bone stress injury. Imaging
      studies are needed to ensure an early and exact diagnosis, because if the
      diagnosis is not delayed most bone stress injuries heal well without
      complications.

PMID- 15239430
TI  - Comparison of intracranial 3D-ToF-MRA with and without parallel acquisition
      techniques at 1.5T and 3.0T: preliminary results.
AB  - PURPOSE: To evaluate the performance of four 3D-ToF magnetic resonance
      angiography (MRA) sequences with and without integrated parallel acquisition
      techniques (iPAT) at 1.5T and 3.0T in imaging intracranial vessels. MATERIAL AND
      METHODS: Seven volunteers and 5 patients (4 aneurysms, 1 AVM) underwent 3D-ToF
      MRA at 1.5T (Magnetom Sonata) and 3.0T (Magnetom Trio) with and without parallel
      acquisition techniques (iPAT) using similarly designed 8-channel phased-array
      head coils. Imaging time of the pulse sequences was set to 7.15 and 7.35 min,
      respectively. Images were analyzed quantitatively by calculating signal-to-noise
      (SNR) and contrast-to-noise (CNR) ratios of proximal M2 segments and
      qualitatively by using a 5-point scale. RESULTS: SNR and CNR were significantly
      higher for both 3D-ToF sequences at 3.0T compared with both pulse sequences at
      1.5T. The highest SNR and CNR were obtained at 3.0T without iPAT. However,
      because of a higher spatial resolution (matrix 512 x 640) visualization of small
      vessel details was best at 3.0T with iPAT. CONCLUSION: Intracranial 3D-ToF-MRA at
      3.0T offers superior image quality compared with 1.5T, particular in the
      delineation of smaller vessels. In contrast to 1.5T, implementation of iPAT at
      3.0T is of additional benefit since the high SNR available at 3.0T allows for
      higher spatial resolution without prolongation of measurement time.

PMID- 15239431
TI  - Factors related to acute hydrocephalus after subarachnoid hemorrhage.
AB  - PURPOSE: To evaluate the influence of the amount and distribution of blood on
      acute ventricular enlargement in subarachnoid hemorrhage (SAH). MATERIAL AND
      METHODS: In a retrospective study, non-contrast computed tomography (CT) images
      of 180 patients with aneurysmal SAH were analysed by two neuroradiologists. The
      amount and distribution of the hemorrhage were scored, and prospective
      hydrocephalus was identified on the basis of acute CT images by calculating the
      cella media index, by measuring the width of the third ventricle, and by visual
      impression. Statistical analysis was done using the logistic regression model,
      analysis of variance, and chi-square test. RESULTS: The incidence of acute
      hydrocephalus was higher among the patients with blood distributed in the
      anterior, lateral, and basal regions (70.8%) than among the patients who did not
      have blood distributed in all three areas (P=0.010). The proportion of acute
      hydrocephalus differed depending on the type of hemorrhage (P<0.001).
      Intraventricular hemorrhage was the most consistent predictive factor in the
      logistic regression model, while the other predictive factors included the total
      blood amount score and the volume of intracerebral hemorrhage. CONCLUSIONS: A
      positive correlation was found between acute hydrocephalus and the amount of
      subarachnoid and, more importantly, intraventricular blood. This is consistent
      with the literature and confirms the current pathophysiologic concepts that the
      acute hydrocephalus following SAH is an obstructive form of hydrocephalus.

PMID- 15239432
TI  - A retained neurointerventional microcatheter fragment in the anterior
      communicating artery aneurysm in multi-slice computed tomography angiography.
AB  - We present a case of multi-slice computed tomography angiography of a 60-year-old
      patient with a retained fragment of microcatheter within an anterior
      communicating artery (AcomA) aneurysm. This is a rare complication of Guglielmi
      detachable coil embolization. After an unsuccessful embolization procedure, the
      patient underwent surgery. During clipping of an AcomA aneurysm, the
      microcatheter traveled up the pericallosal branch of the right anterior cerebral
      artery. Subsequently, the microcatheter fragment did not prevent normal blood
      flow through the artery, and the patient has been doing well without neurological
      sequelae.

PMID- 15239433
TI  - Primary intracranial myxopapillary ependymomas: report of two cases and review of
      the literature.
AB  - Myxopapillary ependymoma is a variant of ependymoma occurring almost exclusively
      in the conus medullaris or filum terminale. Myxopapillary ependymoma found
      primarily in the brain is extremely rare. Two such cases appearing at the 4th
      ventricle and cerebral falx are reported. The imaging features of such tumors are
      a primary cystic mass with strong enhancement at its solid part. Myxopapillary
      ependymoma should be a possible differential diagnosis when an intracranial
      cystic tumor is found.

PMID- 15239434
TI  - Imaging findings of urachal mucinous cystadenocarcinoma associated with
      pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei is an uncommon neoplastic condition in which gelatinous
      fluid-like materials are observed in the peritoneal cavity caused by the
      dissemination of mucinous adenocarcinoma. Although ruptured appendiceal mucocele
      is the most common cause, tumors arising from other organs may also cause
      pseudomyxoma peritonei. We report the imaging findings of an extremely rare case
      of urachal mucinous adenocarcinoma associated with pseudomyxoma peritonei on
      computed tomography and magnetic resonance imaging with histopathologic
      correlation.

PMID- 15239435
TI  - Usefulness of reversed display of soft-copy abdominal radiographs for urinary
      calculi detection.
AB  - PURPOSE: To determine the usefulness of reversed display of soft-copy abdominal
      radiographs for urinary calculi detection. MATERIAL AND METHODS: Sixty
      radiographs with a single urinary calculus less than 5 mm in the long diameter
      (15 in the kidney; 15 in the proximal ureter; 15 in the mid-ureter, 15 in the
      distal ureter) and 15 radiographs without calculi were evaluated. Four readers
      blinded to the presence or absence of urinary calculi on each radiograph reviewed
      the radiographs in the conventional display, reversed display, and combination of
      conventional and reversed displays at 1-week intervals. All images were evaluated
      in random order and the presence or absence of urinary calculi was interpreted
      using the confidence score from 1 to 5. RESULTS: Multireader analysis for calculi
      in all locations showed a greater area under the receiver operating curve for
      combination of the two displays (0.764) than for the conventional display alone
      (0.655) (P=0.031). In the single-reader analysis for calculi in all locations,
      the third reader showed a greater area under the receiver operating curve for the
      reversed display (0.784) than for the conventional display (0.622) (P=0.027).
      Multireader analysis of the calculi in the kidney showed a greater area under the
      receiver operating curve for combination of the two displays (0.824) than for the
      conventional display alone (0.703) (P=0.043). CONCLUSION: The reversed display of
      soft-copy abdominal radiographs may be useful for urinary calculi detection.

PMID- 15239436
TI  - From radiology to imagiatry: keeping pace literally with the progress of our
      discipline.

PMID- 15239437
TI  - Doppler examination of the allografted kidney: a further response.

PMID- 15239438
TI  - [Psychiatry--all the goals have not yet been achieved].

PMID- 15239439
TI  - [Psychiatry--patient infringement designed treatment].

PMID- 15239440
TI  - [Geriatric psychiatry--individuality of nurses' visits].

PMID- 15239441
TI  - [Indicators of quality nursing].

PMID- 15239442
TI  - [Hospitals in the beautiful waves].

PMID- 15239443
TI  - [Chamomile tea in (oral) nursing].

PMID- 15239444
TI  - [On determining the end of life itself].

PMID- 15239445
TI  - [In health as in sickness--nursing questions].

PMID- 15239446
TI  - [Nursing--more than a domestic matter].

PMID- 15239447
TI  - [25 years of stoma care in Germany].

PMID- 15239448
TI  - [Challenges of aging].

PMID- 15239449
TI  - [Insurance against career incompetence].

PMID- 15239450
TI  - [New workplace being sought....].

PMID- 15239451
TI  - [Concerns of new recruits].

PMID- 15239452
TI  - Pet's death rekindles electronic ID debate.

PMID- 15239453
TI  - Emerging zoonoses on the rise.

PMID- 15239454
TI  - Veterinary research needs study begins.

PMID- 15239455
TI  - Pesticide repackaging. What veterinarians need to know.

PMID- 15239456
TI  - Labor Department issues new overtime pay rules.

PMID- 15239457
TI  - Initiative moves one-health model AHEAD. Wildlife Conservation Society fosters
      ecosystem approach.

PMID- 15239458
TI  - The AVMA GHLIT--why wellness remains a top priority. Screenings at convention
      having an effect on veterinarians' health.

PMID- 15239459
TI  - Finds malpractice article slanted.

PMID- 15239460
TI  - Comments on ocular blastomycosis study.

PMID- 15239461
TI  - Suggested treatment for polyarthritis in dogs.

PMID- 15239462
TI  - Shared thoughts on animal rights struggle.

PMID- 15239463
TI  - Shared thoughts on animal rights struggle.

PMID- 15239464
TI  - Shared thoughts on animal rights struggle.

PMID- 15239465
TI  - Shared thoughts on animal rights struggle.

PMID- 15239466
TI  - Shared thoughts on animal rights struggle.

PMID- 15239467
TI  - Shared thoughts on animal rights struggle.

PMID- 15239468
TI  - More on animal friendly curriculums.

PMID- 15239469
TI  - Questions terminology in feline sporotrichosis article.

PMID- 15239470
TI  - A reflection on the ways veterinarians cope with the death, euthanasia, and
      slaughter of animals.

PMID- 15239471
TI  - Serving society first: a time for change in veterinary medicine.

PMID- 15239472
TI  - What is your diagnosis? Fracture of the caudal third of the sacrum with caudal
      distraction and displacement of the caudal portion of the vertebral column and
      dorsal herniation of the rectum.

PMID- 15239473
TI  - Ultrasonography of the urinary tract in small animals.

PMID- 15239474
TI  - Comparison of the standard predictive equation for calculation of resting energy
      expenditure with indirect calorimetry in hospitalized and healthy dogs.
AB  - OBJECTIVE: To determine the level of clinical agreement between 2 methods for the
      measurement of resting energy expenditure (REE). DESIGN: Prospective case series.
      ANIMALS: 77 dogs. PROCEDURE: Oxygen consumption (Vo2) and CO2 production (Vco2)
      were measured with an open-flow indirect calorimeter in healthy (n = 10) and ill
      (67) dogs. Measurements were collected at 3 time periods on 2 days. The Vo2 and
      the Vco2 measurements were then used to calculate the REE values. RESULTS: Mean
      values of measured (MREE) and predicted (PREE) REEs in healthy dogs and a dog
      with medical illnesses or trauma were not significantly different. There was a
      significant difference on day 2 between the MREE and PREE in the group of dogs
      recovering from major surgery. More importantly, there was significant variation
      between the PREE and MREE on an individual-dog basis. The PREE only agreed to
      within +/- 20% of the MREE in 51% to 57% of the dogs. CONCLUSIONS AND CLINICAL
      RELEVANCE: The level of agreement between these two methods for determining the
      24-hour REE was poor in individual dogs. The level of disagreement between the 2
      methods indicates that these methods may not be used interchangeably in a
      clinical setting. Measurement of REE by use of indirect calorimetry may be the
      only reliable method of determining REE in an individual ill or healthy dog.

PMID- 15239475
TI  - Evaluation of laparoscopic-assisted placement of jejunostomy feeding tubes in
      dogs.
AB  - OBJECTIVE: To evaluate feasibility of performing laparoscopic-assisted placement
      of a jejunostomy feeding tube (J-tube) and compare complications associated with
      placement, short-term feedings, and medium-term healing with surgically placed
      tubes in dogs. DESIGN: Prospective study. ANIMALS: 15 healthy mixed-breed dogs.
      PROCEDURES: Dogs were randomly allocated to undergo open surgical or laparoscopic
      assisted J-tube placement. Required nutrients were administered by a combination
      of enteric and oral feeding while monitoring for complications. Radiographic
      contrast studies documented tube direction and location, altered motility, or
      evidence of stricture. RESULTS: Jejunostomy tubes were successfully placed in the
      correct location and direction in all dogs. In the laparoscopic group, the ileum
      was initially selected in 2 dogs, 2 dogs developed moderate hemorrhage at a
      portal site, and 2 J-tubes kinked during placement but were successfully
      readjusted postoperatively. All dogs tolerated postoperative feedings. All dogs
      developed minor ostomy site inflammation, and 1 dog developed bile-induced
      dermatitis at the ostomy site. Despite mild, transient neutrophilia, no
      significant difference was noted in WBC counts between groups. No dog had altered
      gastric motility or evidence of stricture, although the jejunopexy site remained
      identifiable in several dogs at 30 days. CONCLUSIONS AND CLINICAL RELEVANCE:
      Requirements for successful J-tube placement were met by use of a laparoscopic
      assisted technique, and postoperative complications were mild and comparable to
      those seen with surgical placement. Laparoscopic-assisted J-tube placement
      compares favorably to surgical placement in healthy dogs and should be considered
      as an option for dogs requiring enterostomy feeding but not requiring a celiotomy
      for other reasons.

PMID- 15239476
TI  - Evaluation of environmental risk factors for leptospirosis in dogs: 36 cases
      (1997-2002).
AB  - OBJECTIVE: To identify environmental risk factors for leptospirosis. DESIGN:
      Retrospective study. ANIMALS: 36 dogs with leptospirosis and 138 dogs
      seronegative for leptospirosis as determined by microscopic agglutination test
      for antibodies against Leptospira spp. PROCEDURES: Medical records of dogs
      evaluated for leptospirosis from 1997 though 2002 were identified. Owner address
      was used to geocode locations of dogs, and location-specific environmental risk
      factor data were obtained by use of a geographic information system. Risk of
      leptospirosis was estimated by odds ratios, controlling for potential confounding
      by dog age, sex, and breed. RESULTS: Leptospirosis in 19 of the 30 dogs in which
      an infecting Leptospira serovar could be identified was associated with
      Leptospira kirschneri serovar grippotyphosa infection. Dogs in which a diagnosis
      of leptospirosis was made, and dogs with leptospirosis caused by L kirschneri
      serovar grippotyphosa, were more likely to have addresses located in areas
      classified as rural in 1990 but urban in 2000. By use of information on recent
      urbanization and a logistic regression model, the status of 81.6% and 89.8% of
      dogs with leptospirosis and leptospirosis caused by serovar grippotyphosa,
      respectively, were correctly classified. Other environmental variables (proximity
      to streams, recreational areas, farmland, wetlands, areas subject to flooding,
      and areas with poor drainage; annual rainfall; and county cattle or pig
      population) did not significantly improve accuracy of classification. CONCLUSIONS
      AND CLINICAL RELEVANCE: Dogs in periurban areas are at greater risk of
      leptospirosis. Vaccination of dogs in these areas to protect against
      leptospirosis should be considered.

PMID- 15239477
TI  - Tension band stabilization of fractures and luxations of the thoracolumbar
      vertebrae in dogs and cats: 38 cases (1993-2002).
AB  - OBJECTIVE: To determine the outcome of dogs and cats in which a tension band
      technique was used to stabilize traumatic fractures and luxations of the
      thoracolumbar vertebrae. DESIGN: Retrospective study. ANIMALS: 38 client-owned
      animals (22 dogs and 16 cats) weighing between 1.4 and 45 kg (3 and 99 lb).
      PROCEDURE: Medical records of cats and dogs that underwent tension band
      stabilization of thoracolumbar fractures and luxations at the University of
      Zurich between 1993 and 2002 were reviewed. The stabilization technique was a
      modification of a spinal stapling technique with a figure 8 hemicerclage wire
      placed in a tension band fashion across the lesion. Neurologic status, lesion
      location and type, and concomitant traumatic injuries were assessed from the
      medical records and preoperative radiographs. Clinical outcome and complications
      were determined through follow-up examinations or telephone conversations with
      the owners. RESULTS: Complete or satisfactory neurologic recovery was achieved in
      30 (79%) patients. Seven patients were euthanatized (6 owing to poor neurologic
      recovery and 1 owing to implant failure), and 1 dog was managed at home despite
      paraplegia. Clinically, only 4 patients (11%) had evidence of implant or fixation
      failure; all were dogs weighing > 16 kg (35 lb). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that the tension band technique may be appropriate for
      stabilization of fractures and luxations of the thoracolumbar vertebrae in cats
      and small- or medium-sized dogs. In larger dogs, fixation strength may be
      insufficient to stabilize certain fracture types and ancillary external or
      internal fixation methods may be needed.

PMID- 15239478
TI  - Investigation of an outbreak of encephalomyelitis caused by West Nile virus in
      136 horses.
AB  - OBJECTIVE: To describe an outbreak of encephalomyelitis caused by West Nile virus
      (WNV) in horses in northern Indiana. DESIGN: Case series. ANIMALS: 170 horses.
      PROCEDURES: Horses with clinical signs suggestive of encephalomyelitis caused by
      WNV were examined. Date, age, sex, breed, and survival status were recorded.
      Serum samples were tested for anti-WNV antibodies, and virus isolation was
      attempted from samples of brain tissue. Climate data from local weather recording
      stations were collected. An epidemic curve was constructed, and case fatality
      rate was calculated. RESULTS: The most common clinical signs were ataxia, hind
      limb paresis, and muscle tremors and fasciculations. Eight horses had been
      vaccinated against WNV from 2 to 21 days prior to the appearance of clinical
      signs. West Nile virus was isolated from brain tissue of 2 nonvaccinated horses,
      and anti-WNV IgM antibodies were detected in 132 nonvaccinated horses; in 2 other
      nonvaccinated horses, anti-WNV antibodies were detected and WNV was also isolated
      from brain tissue. Thirty-one (22.8%) horses died or were euthanatized. The peak
      of the outbreak occurred on September 6, 2002. Ambient temperatures were
      significantly lower after the peak of the outbreak, compared with prior to the
      peak. CONCLUSIONS AND CLINICAL RELEVANCE: The peak risk period for
      encephalomyelitis caused by WNV in northern Indiana was mid-August to mid
      September. Reduction in cases coincided with decreasing ambient temperatures.
      Because of a substantial case fatality rate, owners of horses in northern Indiana
      should have their horses fully protected by vaccination against WNV before June.
      In other regions of the United States with a defined mosquito breeding season,
      vaccination of previously nonvaccinated horses should commence at least 4 months
      before the anticipated peak in seasonal mosquito numbers, and for previously
      vaccinated horses, vaccine should be administered no later than 2 months before
      this time.

PMID- 15239479
TI  - Association between race history and risk of superficial digital flexor tendon
      injury in Thoroughbred racehorses.
AB  - OBJECTIVE: To determine whether race history, including the number of races and
      total race distance, was associated with risk of superficial digital flexor
      tendon (SDFT) injury in Thoroughbred racehorses in Japan. DESIGN: Matched case
      control study. ANIMALS: 515 Thoroughbred racehorses (case horses) that sustained
      an SDFT injury during training or racing in Japan during 2002 and 951 horses
      (control horses) without SDFT injury that were matched with case horses on the
      basis of age and month of the latest race. PROCEDURE: Variables related to race
      history were compared between case and control horses by means of conditional
      logistic regression. RESULTS: The odds of SDFT injury increased as mean race
      distance and mean body weight at race time increased. Compared with females that
      had never competed in steeplechase races, males regardless of steeplechase race
      history and females that had competed in steeplechase races had higher odds of
      SDFT injury. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that longer mean
      distance per race, heavier mean body weight at race time, steeplechase
      experience, and sex (male) increased the risk of SDFT injury in Thoroughbred
      racehorses.

PMID- 15239480
TI  - Excision as treatment of dermal melanomatosis in horses: 11 cases (1994-2000).
AB  - OBJECTIVE: To determine whether excision was an acceptable treatment for dermal
      melanomatosis in horses. DESIGN: Retrospective study. ANIMALS: 11 horses with
      dermal melanomatosis involving the perineal, perianal, or perirectal region or
      ventral surface of the tail in which treatment consisted of tumor excision.
      PROCEDURE: Medical records were reviewed. Follow-up information was obtained from
      owners through telephone interviews. RESULTS: 9 of the 11 horses were alive at
      the time of follow-up interviews. None of the horses had regrowth at the surgery
      site where the primary tumor was removed. There were no confirmed clinical signs
      of internal metastasis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      excision of dermal melanomatosis in horses may be a reasonable treatment option.

PMID- 15239481
TI  - Seroprevalence of Mycobacterium avium subsp paratuberculosis infection among
      dairy cows in Colorado and herd-level risk factors for seropositivity.
AB  - OBJECTIVE: To estimate seroprevalence of Mycobacterium avium subsp
      paratuberculosis (MAP) infection among adult dairy cows in Colorado and determine
      herd-level factors associated with the risk that individual cows would be
      seropositive. DESIGN: Cross-sectional observational study. ANIMALS: 10,280 adult
      (> or = 2 years old) dairy cows in 15 herds in Colorado. PROCEDURE: Serum samples
      were tested with a commercial ELISA. A herd was considered to be infected with
      MAP if results of mycobacterial culture of > or = 1 individual cow fecal sample
      were positive or if > or = 1 culled cow had histologic evidence of MAP infection.
      RESULTS: 424 of the 10,280 (4.12%) cows were seropositive. Within-herd prevalence
      of seropositive cows ranged from 0% to 7.82% (mean, 2.6%). Infection was
      confirmed in 11 dairies. Cows in herds that had imported > or = 8% of their
      current herd size annually during the preceding 5 years were 3.28 times as likely
      to be seropositive as were cows in herds that imported < 8%. Cows in herds with >
      or = 600 lactating cows were 3.12 times as likely to be seropositive as were cows
      in herds with < 600 lactating cows. Cows in herds with a history of clinical
      signs of MAP infection were 2.27 times as likely to be seropositive as were cows
      in herds without clinical signs. CONCLUSIONS AND CLINICAL RELEVANCE: Annual
      importation rate, herd size, and whether cows in the herd had clinical signs
      typical of MAP infection were associated with the risk that individual cows would
      be seropositive for MAP infection.

PMID- 15239482
TI  - Effectiveness of inactivated trivalent influenza vaccine in long-term care
      institutions, Toronto, 2003-2004.

PMID- 15239483
TI  - An Advisory Committee Statement (ACS). National Advisory Committee on
      Immunization (NACI). Statement on influenza vaccination for the 2004-2005 season.

PMID- 15239484
TI  - Epidemiology and burden of cardiovascular disease.
AB  - Coronary heart disease (CHD) is the leading cause of death in the United States.
      The rate of CHD and CHD death varies across racial groups, with higher rates
      among black men and women than among white men and women. The development of CHD
      is promoted by major CHD risk factors--dyslipidemia, hypertension, and smoking.
      These risk factors are independently associated with CHD risk and are common
      among adults in the United States. Diabetes mellitus is also a significant
      contributor to CHD risk and is associated with risk of a CHD event equivalent to
      that conferred by the presence of prior CHD. Metabolic syndrome, a related
      condition, also confers a high risk for CHD as well as for the development of
      type 2 diabetes. Diabetes and metabolic syndrome are characterized by the
      presence of central obesity and insulin resistance, which result in dyslipidemia,
      hypertension, and cardiovascular derangements that promote CHD. Diabetes and
      metabolic syndrome illustrate the significance of risk factor clustering, which
      contributes to CHD risk through the additive effect of each risk factor.
      Diabetes, metabolic syndrome, and risk factor clustering in general are becoming
      more prevalent, which illustrates the need for better CHD prevention strategies
      aimed at risk factor control. The pathologic process associated with risk factor
      clustering also contributes to the higher CHD burden among black men and women,
      who have a higher prevalence of risk factor clustering and type 2 diabetes.
      Furthermore, despite having a higher CHD risk, black men and women are less
      likely to receive adequate treatment or control of risk factors, including
      dyslipidemia or hypertension. Eliminating disparities among population groups
      will thus require aggressive efforts focused on risk assessment, guideline
      adherence, and risk factor control in populations in need.

PMID- 15239485
TI  - Assessing coronary heart disease risk with traditional and novel risk factors.
AB  - Cardiovascular disease is the leading cause of death in the industrialized world,
      and a number of well-characterized factors, including advanced age, hypertension,
      dyslipidemia, diabetes, and smoking, contribute to cardiovascular risk.
      Integration of these factors using the Framingham calculation estimates the
      absolute 10-year risk for coronary heart disease (CHD), which can be used to
      guide therapy. Recent studies have demonstrated that additional markers,
      including elevated lipoprotein(a), homocysteine, sitosterol, and particularly C
      reactive protein (CRP), are also associated with increased risk for CHD. In
      particular, high-sensitivity CRP has been shown to identify patients with high
      CHD risk who may not have elevated low-density lipoprotein cholesterol (LDL-C)
      and may add to the predictive value of the Framingham functions for CHD risk
      assessment. Assessment of global risk is particularly important in lipid
      management, as the LDL-C target goals are determined by risk category.

PMID- 15239486
TI  - The importance of aggressive lipid management in patients at risk: evidence from
      recent clinical trials.
AB  - Clinical trials that evaluate more aggressive cholesterol reduction in a broader
      range of patients at high risk for coronary heart disease (CHD) are needed to
      fill gaps in our understanding of the impact of lipid-lowering therapy on risks
      for clinical events and mortality. This paper briefly reviews results from recent
      landmark studies that have evaluated the benefits of aggressive lipid-lowering
      therapy in patients with, or at risk for, CHD. The Reversing Atherosclerosis with
      Aggressive Lipid Lowering (REVERSAL) study demonstrated that aggressive treatment
      with atorvastatin was significantly more effective than less aggressive therapy
      with pravastatin in slowing the progression of atherosclerosis in patients with
      symptomatic CHD. Results from two large-scale clinical end-point trials, the
      Heart Protection Study (HPS) and the Anglo-Scandinavian Cardiac Outcomes Trial
      Lipid Lowering Arm (ASCOT-LLA), have shown that aggressive lipid-lowering
      treatment in patients with relatively low baseline levels of low-density
      lipoprotein cholesterol (LDL-C) significantly reduces CHD risk. Taken together,
      the results of these landmark trials not only support aggressive lipid lowering
      in patients at risk for CHD, but also suggest that greater LDL-C reductions may
      improve outcomes across a wide range of patients.

PMID- 15239487
TI  - Cholesterol metabolism and therapeutic targets: rationale for targeting multiple
      metabolic pathways.
AB  - The liver is the major regulator of the plasma low density lipoprotein
      cholesterol (LDL-C) concentration because it is not only the site of formation of
      very low density lipoproteins (VLDL), the precursors of most LDL in the
      circulation, but it is also the organ where the bulk of receptor-mediated
      clearance of LDL takes place. The liver also initially clears all the cholesterol
      that is absorbed from the small intestine. The absorption of excess cholesterol
      can potentially increase the amount of cholesterol stored in the liver. This, in
      turn, can result in increased VLDL secretion, and hence LDL formation, and also
      downregulation of hepatic LDL receptor activity. Such events will potentially
      increase plasma LDL-C levels. The converse situation occurs when cholesterol
      absorption is inhibited. Cholesterol enters the lumen of the small intestine
      principally from bile and diet. The major steps involved in the absorption
      process have been characterized. On average, about half of all cholesterol
      entering the intestine is absorbed, but the fractional absorption rate varies
      greatly among individuals. While the basis for this variability is not
      understood, it may partly explain why some patients respond poorly or not at all
      to statins and other classes of lipid-lowering drugs. There are few data relating
      to racial differences in cholesterol absorption. One study reported a
      significantly higher rate in African Americans compared with non-African
      Americans. Multiple lipid-lowering drugs that target pathways involving the
      absorption, synthesis, transport, storage, catabolism, and excretion of
      cholesterol are available. Ezetimibe selectively blocks cholesterol absorption
      and lowers plasma LDL-C levels by an average of 18%. When ezetimibe is
      coadministered with lower doses of statins, there is an additive reduction in LDL
      C level, which equals the reduction achieved with maximal doses of statins alone.
      Dual inhibition of cholesterol synthesis and absorption is an effective new
      strategy for treating hypercholesterolemia.

PMID- 15239488
TI  - Optimizing lipid lowering in patients at risk.
AB  - The efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C)
      and reducing coronary heart disease risk is well established; however, recent
      evidence suggests that more aggressive lipid management, even beyond achievement
      of currently recommended LDL-C goals, may provide additional clinical benefits. A
      novel approach to the aggressive lowering of LDL-C is the combination of statins
      with agents that affect different aspects of cholesterol metabolism. Because
      absorption of cholesterol is an important contributor to cholesterol balance, the
      simultaneous inhibition of cholesterol absorption and cholesterol synthesis is an
      attractive approach to achieving greater LDL-C reductions. In clinical trials,
      the combination of the cholesterol absorption inhibitor ezetimibe with a statin
      resulted in greater improvements in lipids than statin monotherapy and allowed a
      greater percentage of patients to achieve treatment goals. In addition, this
      combination may offer benefits through reduction of phytosterols, chylomicron
      remnants, and C-reactive protein. Several ongoing trials are evaluating whether
      the benefit of simultaneously blocking cholesterol synthesis and intestinal
      cholesterol absorption translates into better clinical outcomes.

PMID- 15239489
TI  - Time and rate measures in choice transitions.
AB  - Three experiments with pigeons studied the relation between time and rate
      measures of behavior under conditions of changing preference. Experiment 1
      studied a concurrent chain schedule with random-interval initial links and fixed
      interval terminal links; Experiment 2 studied a multiple chained random-interval
      fixed-interval schedule; and Experiment 3 studied simple concurrent random
      interval random-interval schedules. In Experiment 1, and to a lesser extent in
      the other two experiments, session-average initial-link wait-time differences
      were linearly related to session-average response-rate differences. In Experiment
      1, and to a lesser extent in Experiment 3, ratios of session-average initial-link
      wait times and response rates were related by a power function. The weaker
      relations between wait and response measures in Experiment 2 appear to be due to
      the absence of competition between responses. In Experiments 1 and 2, initial
      link changes lagged behind terminal-link changes. These findings may have
      implications for the relations between fixed- and variable-interval procedures
      and suggest that more attention should be paid to temporal measures in studies of
      free-operant choice.

PMID- 15239490
TI  - Bouts of responding on variable-interval schedules: effects of deprivation level.
AB  - Rats obtained food pellets on a variable-interval schedule of reinforcement by
      nose poking a lighted key. After training to establish baseline performance (with
      the mean variable interval set at either 60, 120, or 240 s), the rats were given
      free access to food during the hour just before their daily session. This
      satiation operation reduced the rate of key poking. Analysis of the interresponse
      time distributions (log survivor plots) indicated that key poking occurred in
      bouts. Prefeeding lengthened the pauses between bouts, shortened the length of
      bouts (less reliably), and had a relatively small decremental effect on the
      response rate within bouts. That deprivation level affects mainly between-bout
      pauses has been reported previously with fixed-ratio schedules. Thus, when the
      focus is on bouts, the performances maintained by variable-interval schedules and
      fixed-ratio schedules are similarly affected by deprivation.

PMID- 15239491
TI  - Repeated post- or presession cocaine administration: roles of dose and fixed
      ratio schedule.
AB  - Effects of repeated administration of cocaine to animals behaving under operant
      contingencies have depended on when the drug is given. Moderate doses given
      presession have generally led to a decrease in the drug's effect, an outcome
      usually referred to as tolerance. When these same doses have been given after
      sessions, the usual result has been no change or an increase in the drug's
      effects, with the latter usually referred to as sensitization. In the present
      study, repeated postsession administration of a relatively small dose of cocaine
      (3.0 or 5.6 mg/kg) to pigeons responding under a multiple fixed-ratio 5, fixed
      ratio 100 schedule of food presentation generally resulted in tolerance to the
      rate-decreasing effects of the drug. When the same dose was given before
      sessions, little additional tolerance was observed, although some subjects showed
      further tolerance in the small-ratio component. A regimen of repeated postsession
      injection of larger (10.0-23.0 mg/kg) doses suppressed key pecking during the
      session; responding resumed following discontinuation of postsession
      administrations. Effects of postsession administration of cocaine, therefore,
      depended on the dose, with smaller doses leading to tolerance and larger ones to
      suppression of behavior during the session. Effects of postsession drug
      administration of either small or large doses were not related to whether effects
      of postsession drug were experienced mainly in the operant test chamber or in the
      pigeon's home cage. The results with large postsession doses are compatible with
      a view that the drug acted as a Pavlovian unconditional stimulus, with the
      session-related stimuli acting as a long-duration Pavlovian conditional stimulus.
      Tolerance following postsession administration of the smaller doses challenges
      the view that it depended on experiencing the drug's effects while the arranged
      reinforcement contingencies were in effect.

PMID- 15239492
TI  - Psychology in the year 2000.

PMID- 15239493
TI  - [Surgery for children and adolescents. Post-operative phase].
AB  - The authors explain the third and last phase in the surgical process, the post
      operative phase. The authors propose a standardized model of nursing care for
      children and adolescents. The third and last phase in the surgical process
      commences at the moment the child arrives in the recovery room and lasts until
      he/she is released from the hospital. This phase includes the treatment applied
      in the recovery room and later in a hospital ward or in the child's home. The
      authors use the Gordon Functional Health Patterns. Special emphasis is given to
      the perception-management health pattern, the nutritional-metabolic pattern, the
      elimination pattern, the exercise-activity pattern, and the cognitive-perception
      pattern. Of special importance is the vigilance during the first post-operative
      hours, as well as the child's parenteral nutrition or total parenteral nutrition,
      TPN, and the evaluation of pain according to the age of the child. The authors
      select the NANDA (North American Nursing Diagnosis Association) Nursing Diagnoses
      which appear most frequently in this post-operative phase.

PMID- 15239494
TI  - [Collagen powder: hydrocolloidal dressings. Their effectiveness in
      radiodermatitis].
AB  - The authors analyze the effectiveness of a collagen cicatrizant powder for use in
      treating radiodermatitis compared with extra fine hydrocolloidal dressings by
      evaluating skin lesions according to the Radiation Therapy Oncology Group (RTOG)
      intensity scale. As the same time, the authors evaluate the patient's opinion
      regarding the treatment he/she receives. This study was carried out in the
      Valladolid University Clinical Hospital's Department of Radiotherapy. This study
      showed that the Catrix brand dressing is more effective than hydrocolloidal
      dressings as a treatment of lesions caused by radiodermatitis. Both the nursing
      personnel and patients involved in this study rated this Catrix product higher
      than those hydrocolloidal dressings products tested.

PMID- 15239495
TI  - [The intra bone passage and nursing].
AB  - The authors confirm the utility of the intra bone passage as a means of emergency
      vascular access when the installation of a peripheral and/or central venous
      passage is difficult or impossible when attending critically ill patients as
      another additional technique available to Nursing when caring for a critically
      ill patient. From the reference articles reviewed, the authors deduce that intra
      bone vascular access provides a passage to the vascular system which permits
      rapid, easy and efficient access, especially when attending children under the
      age of six. The use of the intra bone passage is justified whenever medical
      personnel take more than 90 seconds or have three failed tries to insert a
      peripheral venous tube in patients who are critically ill or unstable. The
      anatomical zones which are the most appropriate to puncture in children are the
      proximal and distal part of the tibia and the distal section of the femur. This
      intra bone passage permits the administering of liquids and drugs, just as a
      peripheral venous passage does. Both the complications and the countermeasures
      are minimal.

PMID- 15239496
TI  - [Constipation opposes well-being].
AB  - Constipation has an effect in traumatology and orthopedic surgery as a real and
      potential problem capable of increasing disease-caused mortality related to the
      slowness of feces in the intestinal tract; furthermore, constipation contributes
      manifestly to an alteration in a patient's well-being. In spite of this, there
      are very few studies in this area of knowledge in nursing and the majority of
      cases, constipation is considered to be a secondary problem among general
      treatment plans for trauma patients' linked to a syndrome of disuse due to being
      bedridden. In this study, the authors have tried to point out the magnitude and
      the clinical importance constipation has in trauma ward patients as well as
      create a treatment protocol which has some specific treatments which permit a
      standardization of nursing care provided to at risk patients. To develop this,
      the authors have carried out a comparative study following the directions
      established by the Process of Nursing Treatment as the paradigm for the
      application of the scientific method in professional practice. The evaluation of
      the results obtained in this study let the authors conclude that the adoption of
      this standardized protocol which we present for treatment of constipation
      suffered by trauma ward patients improves the pattern of bowel movements by
      patients hospitalized with fractures in their inferior extremities without having
      backbone complications.

PMID- 15239497
TI  - [Nursing and Europe].
AB  - A European environment is a reality; therefore, nurses should adjust their
      working patterns to conform with this context. The variables which shall
      determine the future of nursing are: globalization, governmental sanitary
      policies, demographic changes, and new treatment necessities. Indispensable
      elements to confront the future as one should include having a clear idea what
      one's own treatment role is and knowing what are the treatment necessities which
      our continually more complex population demands.

PMID- 15239498
TI  - [The nursing field in education].
AB  - "Campus Extens" is a new correspondence course/open university educational
      project which makes use of new technologies in communication such as the Internet
      or videoconferences for the diffusion of its course content. This program
      commenced in 1997 as a provisional experimental program at the University of the
      Balearic Islands; at present, after six years up and running, this program is an
      established program. Classes in nursing were introduced as part of this program,
      due to a request by the Nursing Department, in an experimental provisional format
      since the academic year 2001-02 hoping to integrate new educational technologies
      and bring these closer to students in the Balearic Isles who find it difficult to
      attend traditional classes which are taught on the Palma campus and at the same
      time to make future correspondence courses possible. Taking the pedagogical
      materials which correspond to the Nursing Fundamentals course as an example, the
      authors describe the characteristics of this system, the educational model
      implemented, the didactic strategies which are used in this virtual classroom
      environment, as well as the methodological arrangement and the didactic materials
      which have been developed for this program. Finally, the authors want to point
      out that the participation of Nursing in this program has enabled the Nursing
      Department to respond to the educational and professional demands of the
      University of the Balearic Islands, to reflect critically about teaching
      methodology, to bring the School of Nursing and Physiotherapy closer to our
      university community and to design new projects for future correspondence/open
      university courses.

PMID- 15239499
TI  - [Producing intravenous medications in a pharmacy].
AB  - The authors explain the different intravenous mixtures and the types of preloaded
      syringes elaborated in a centralized unit, analysing their profitability and
      evaluating their repercussion on the daily work nurses have to perform. This
      study was carried out in the Hospital de Poniente in Almeria, a county hospital
      which has 165 beds. The hospital authorities defined those medications which were
      chosen to be prepared in a centralized unit in the Pharmacy Service of the
      hospital and they drew up a list/guide of their corresponding conservation
      conditions. The authorities determined the time which nursing personnel in the
      various hospital units would employ in the elaboration of these medications and
      compared that with the time employed in the Pharmacy Service.

PMID- 15239500
TI  - [Human pediculosis, or how to treat lice infestations?].
AB  - The author reports on relevant aspects of pediculosis humanus, citing the lice
      species implicated, their location in the zones affected by lice infestations on
      human bodies and in their clothing; furthermore, he describes the most frequent
      lesions produced by lice, the adequate handling of lice infestations and their
      treatment. Lice are not a recent phenomenon; probably the lice which we encounter
      today acting as a parasite on humans is very similar to lice which infested
      humans centuries ago.

PMID- 15239501
TI  - [Medications, globalization, and developing countries].
AB  - The author reviews pending problems related to medication from the perspective of
      underdeveloped nations and which options exist to deal with them.

PMID- 15239502
TI  - [Accident prevention in childhood].

PMID- 15239503
TI  - North Carolina Institute of Medicine Task Force on the North Carolina Nursing
      Workforce (2004).
AB  - North Carolina is indeed fortunate to have avoided many of the extreme shortages
      of nurses reported in other states. Yet, there are important developments on the
      horizon that have the potential to cause such shortages. Taking action today to
      expand the production of new nurses, enhance their education, augment school-to
      work transitions, and improve the nursing workplace environment can help reduce
      the likelihood of a future nursing workforce crisis. Some steps will require new
      financial commitments either from public or private sources. Others will require
      a renewed commitment on the part of employers, educators, regulators and the
      nursing community. However, these steps are necessary if we are to recruit and
      retain well-prepared and motivated nurses who are needed to meet our healthcare
      needs now and in the future. Nursing, especially nursing at the bedside in
      hospitals and in long-term care, requires increasingly sophisticated technical
      skills and continues to demand intellectual, physical and emotional energy beyond
      what would be required in many other professions and occupations. It is hoped
      that the recommendations offered here will help focus the efforts of legislators,
      educators, employers, the nursing community, trade associations, foundations and
      the public at large to ensure an adequate supply of well-trained nursing
      personnel for the future.

PMID- 15239504
TI  - Why is nursing important?

PMID- 15239505
TI  - Employers and the nursing workforce: seeking local solutions to a national
      problem.

PMID- 15239506
TI  - The long-term care nursing workforce: who will take care of our rapidly growing
      aging population?

PMID- 15239507
TI  - Our future nursing workforce: a regulatory perspective.

PMID- 15239508
TI  - North Carolina's community college commitment to nursing education.

PMID- 15239509
TI  - The University of North Carolina System and nursing in North Carolina.

PMID- 15239510
TI  - Private colleges and university nursing programs in North Carolina.

PMID- 15239511
TI  - Are hospital-related nursing programs the answer?

PMID- 15239512
TI  - How LPNs can be part of the solution.

PMID- 15239513
TI  - A critical need for a more diverse nursing workforce.

PMID- 15239514
TI  - Developing an adequate and high quality nurse aide workforce in North Carolina.

PMID- 15239515
TI  - The North Carolina Area Health Education Centers' role in addressing nursing
      workforce issues.

PMID- 15239516
TI  - Transitioning from school-to-work: one successful model.

PMID- 15239517
TI  - Advanced practice registered nurses: current problems and new solutions.

PMID- 15239518
TI  - North Carolina Center for Nursing and the nursing workforce.

PMID- 15239519
TI  - Mental health reform.

PMID- 15239520
TI  - 2002 North Carolina live births attended by certified nurse midwives.

PMID- 15239521
TI  - Well-kept secret. Despite a lack of clearly defined standards, hospitals are
      under increasing pressure to publicly report charity-care figures.
AB  - Because hospitals have wildly divergent policies on reporting how much charity
      care they deliver, some fear the standards are so lax that they won't be able to
      defend their tax exemptions in court. Charity-care data are "all over the map,"
      says Susan Sherry, left, deputy director of Community Catalyst.

PMID- 15239522
TI  - Attacking abuse. Lawsuits plague not-for-profits, AHA.

PMID- 15239523
TI  - Sounding an alarm. Healthcare groups protest possible spending caps.

PMID- 15239524
TI  - Really special treatment. AHA seeks update on federal antitrust statements.

PMID- 15239525
TI  - Taking a closer look. AMA studying impact of specialty hospitals.

PMID- 15239526
TI  - Formidable foe. CalPERS fights to block WellPoint-Anthem merger.

PMID- 15239527
TI  - A study best forgotten. Moderating costs aren't good news for an industry in need
      of reform.

PMID- 15239528
TI  - Restring the safety net. Incremental changes aren't enough; a new system of care
      is needed.

PMID- 15239529
TI  - A new public face. Changes in governance help public hospitals gain a stronger
      financial footing, but it doesn't mean an end to their struggles.

PMID- 15239530
TI  - By the numbers. 25 busiest community hospital emergency departments. Ranked by
      number of emergency room visits in 2002.

PMID- 15239531
TI  - [Clinical significance of persistent or recurrent fever during the treatment of
      infective endocarditis].
AB  - Patients with infective endocarditis (IE) were studied to assess incidence,
      clinical features and mortality in a population with either persistent (PF) or
      recurrent fever (RF) during treatment. A sample of 81 patients was evaluated. Of
      these, 46 patients (56.8%) had fever during treatment: 35 had PF and 16 had RF
      (Group 1). This group was compared with 35 patients with IE without fever (Group
      2). Age, sex, in-hospital days, nosocomial acquisition, delay in diagnosis, and
      co-morbidities were similar among each group. The aortic and tricuspid valve
      compromise, and Staphylococcus aureus as etiologic agent were more frequent in
      Group 1 (although not significantly). However, the development of complications
      (95.6 vs. 65.7%), renal dysfunction (58.6 vs. 31.4%), major vessel embolization
      (60.8 vs. 34%), microvascular phenomena (43.4 vs. 17.1%), infections with MRSA
      (22.2 vs. 4%) and valvular surgery (34.7 vs. 11.4%) were significantly higher in
      Group 1 (p<0.05). The most common causes of PF were microvascular phenomena
      (14/32 patients), systemic and pulmonary embolization (10), valvular abscesses
      (5), persistent bacteremia (4) and mycotic aneurysm (2). On the other hand,
      phlebitis (6/16), drug hypersensitivity (3) and nosocomial infections (3) were
      related with RF. The overall mortality was 39.5%, distributed as follows: 52.2%
      of Group 1 and in 22.9% of Group 2 (p=0.007). The presence of comorbidities,
      major vessel embolization, heart failure, MRSA infection and inappropriate
      initial antibiotic therapy were significantly associated with the increased
      mortality in Group 1 (p<0.05). We propose an evaluation method during the
      treatment of patients affected by this type of fever.

PMID- 15239532
TI  - [Indications of conventional chest physiotherapy in acute bronchiolitis].
AB  - To evaluate the benefits of conventional chest physiotherapy in acute
      bronchiolitis, 32 patients were allocated in a randomized controlled trial, 16
      were given twice daily chest physiotherapy compared with 16 controls who were not
      given chest physiotherapy. The treatment group showed a mean clinical score for
      respiratory disability at admission of 5.56 (+/- 1.96), and 3.25 (+/- 1.27) when
      discharged. The control group presented a score of 5.75 (+/- 1.61) and 3.12 (+/-
      1.30), p=0.77 and p=0.76 respectively. The mean length of illness in hospital in
      the treatment group was 4.00 (+/- 2.00) vs 3.87 (+/- 1.30) in the control group,
      p=0.84. Chest physiotherapy does not produce clinically important benefits in the
      treatment of acute bronchiolitis.

PMID- 15239533
TI  - [Survey on changes in asthma treatment and management].
AB  - A total of 518 chest physicians selected at random from a national list
      participated in a survey on asthma management. This paper dealt with queries
      about diagnostic procedures, methods for recognizing life-threatening asthma
      attacks, patient education and treatment for acute asthma in adults and in
      children older than 6 years. A total of 198 replies were received (38.2% of
      questionnaires mailed). A mean score of frequency of use (from 0 = never to 3 =
      always) was used for assessing the responses. Results were compared with a
      similar survey performed in 1994, disclosing a satisfactory trend in diagnostic
      tests with the bronchodilator test and in oral steroid courses (2.74 +/- 2.3 vs
      2.30 +/- 1.05 and 1.26 +/- 0.96 vs 0.98 +/- 0.84, respectively). Skin tests were
      less used (0.50 +/- 0.83 vs 0.88 +/- 1.08). Results reporting how to assess the
      severity of asthma attacks, such as taking into account symptoms or drop in PEFR,
      were more frequent in the present study (2.65 +/- 0.66 vs 2.29 +/- 0.90 and 1.93
      +/- 1.05 vs 1.51 +/- 1.20, respectively). PEFR or spirometry used by the
      physician for assessing severity of asthma attacks was not always performed and
      its comparison was no better than in 1994 (2.14 +/- 1.04 vs 2.13 +/- 0.70). Data
      regarding patient information and education ranked equal or better than in the
      1994 survey. For the treatment of acute severe episodes, almost all responders in
      the present study chose inhaled 12 agonists (IBA) for adults and children, thus
      improving with respect to the previous study (first option 85.3 vs 57.5% and 81.0
      vs 63.4%, respectively). For maintenance therapy, a good trend was also observed
      with more responders who now chose inhaled steroid (IS) as a first choice
      formulation, specially in children (2.09 +/- 1.01 vs 1.61 +/- 1.00). The average
      normal and maximal daily doses of IS for adults and children were higher than in
      1994 and were now in agreement with recommended doses. The recommendation of
      short acting IBA for treating and preventing symptoms was noticeably less
      frequent in the present study either for adults or for children (0.40 +/- 0.78 vs
      1.23 +/- 1.10 and 0.21 +/- 0.58 vs 1.23 +/- 1.00, respectively).
      Hyposensitization was less recommended than in 1994. Despite a tendency to
      improve treatment and management, considerable differences with asthma guidelines
      still remain.

PMID- 15239534
TI  - Mutations in CFTR gene and clinical correlation in Argentine patients with
      congenital bilateral absence of the vas deferens.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) is a form of male
      infertility in which mutations in the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene have been identified. Here we identify different mutations
      of CFTR and the poly-T variant of intron 8 (IVS8) in Argentine patients and
      analyze sweat test values and clinical characteristic related to Cystic Fibrosis
      (CF). For counseling purposes the two most frequent mutations in Argentine CF
      population: deltaF508 and G542X were screened in wives. In all cases, it was
      possible to reduce the risk of CF/CBAVD descendants in these couples because none
      of the mutation were found in the 36 samples. Eight patients (23%) showed
      abnormal chloride values (> 60 mmol/l). A second group of 6 patients (18%) had
      borderline values of sweat chloride (40-59 mmol/l). We defined another group with
      6 patients (18%), with normal sweat chloride levels (30-39 mmo/l) and a fourth
      group of 14 (41%) patients with sweat chloride below 30 mmol/l. deltaF508, the
      most frequent CF mutation in the Argentine population, was found on 15 of the 72
      chromosomes (21%), R117H mutation was detected on 2 of 62 chromosomes (3%). Only
      one R347P allele was found on 28 chromosomes analyzed (2%). On a sample of 27
      patients, IVS8 analysis showed a frequency of 6/56 chromosomes (11%) of 5T
      allele. Even though these findings present an improvement in the detection of
      mutations related to clinical correlations in Argentine CBAVD population, the
      search for other common and uncommon mutations should be continued.

PMID- 15239535
TI  - General physicians and the management of heart failure in an Argentine
      population.
AB  - The aim of this study was to assess how general physicians (GP) think that heart
      failure (HF) should be managed and how they implement their knowledge. It was
      conducted in Buenos Aires City and suburban area, with the collaboration of 5
      cardiologists, and 29 GP who were selected randomly, and were asked to keep a log
      of all patients they saw with HF. The methodology was similar to that employed in
      an international initiative named "Improvement" already performed in Europe. Data
      were obtained of 220 note patients. GP knowledge and perceptions about the
      management of HF were assessed initially with a "perception survey", and later on
      how a representative sample of patients was managed, with an "actual practice
      survey". The electrocardiogram and the chest radiograph were recorded in most
      patients (approximately equal to 90%), but the echocardiogram only in 67% of
      cases. Forty percent of the patients had history of myocardial infarction and
      ischaemic heart disease, but exercise test was not considered as a potential
      diagnostic test and was recorded only in 16% of the patient records. Likewise
      coronary angiogram was performed in 7% of patients. Only 23% of the patients had
      a left ventricular ejection fraction test result documented in their charts. In
      practice, 43% of GP patients were receiving an ACE inhibitor and one third
      betablockers. Only 9% received these drugs in combination. At the last interview,
      50% had hypertension (blood pressure > or = 140/90) and 15% had not recorded this
      data in patients notes. This study identified, in a random sample of GP of Buenos
      Aires City and suburbs, that management of HF was less than optimal.

PMID- 15239536
TI  - Thyroid autoantibodies in autoimmune diseases.
AB  - Abnormalities in the thyroid function and thyroid autoantibodies have been
      frequently described in patients with autoimmune diseases but seldom in
      antiphospholipid syndrome patients. In order to determine the prevalence of
      thyroid function and autoimmune abnormalities, we compared serum thyrotropin
      (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and
      antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25
      patients with rheumatoid arthritis and 13 patients with antiphospholipid syndrome
      to a control group of 113 healthy individuals. Evaluation included a thorough
      clinical examination with particular attention to thyroid disease and a serologic
      immune profile including rheumatoid factor, antinuclear and anticardiolipin
      antibody measurements. Subclinical hypothyroidism (4.2<TSH<10 mU/L) was diagnosed
      in five patients (8%), and subclinical hyperthyroidism (undetectable<TSH<0.34
      mU/L) in four patients (6%). Anti-thyroglobulin (TgAb) and/or anti
      thyroperoxidase (tPOAb) antibodies were present in 21/63 (33%) of our patients:
      13/25 (52%) of the systemic sclerosis cases, 8/25 (32%) of the rheumatoid
      arthritis patients, but 0 (0/13) of the antiphospholipid syndrome patients. In
      conclusion, our data confirm a high prevalence of silent autoimmune thyroid
      diseases in association with systemic sclerosis and rheumatoid arthritis
      (p<0.02), but not with antiphospholipid syndrome. Elevated antibody titres may
      reflect an epiphenomenon of the underlying autoimmune disorders and play an
      additive role in the development of the euthyroid sick syndrome in these
      patients, but our data suggest that the antiphospholipid syndrome presents a
      different pattern of response. Subclinical thyroid diseases should be considered
      when evaluating patients with autoimmune diseases.

PMID- 15239537
TI  - [Spatio-temporal variability in the transmission of dengue in Buenos Aires City].
AB  - Cases of dengue detected in Buenos Aires City between 1999 and 2000 confirmed the
      possibility of epidemic outbreaks. The activity of its vector Aedes aegypi was
      monitored to study the spatial and temporal risk of dengue transmission. Adult
      oviposition activity of Aedes aegypti showed an heterogeneous spatio-temporal
      distribution pattern. It was detected between October and May. The vector was
      detected from spring to fall in the Northern, Western and Southern areas of the
      city (periphery) and only in summer in the Eastern part (downtown-river). The
      proportion of infested sites differed between the three periods but the infested
      areas coincided spatially. Although a spatial and temporal heterogeneity exists,
      the pattern repeated itself during the three periods suggesting stable dynamics.
      The not infested areas presented the highest population and employees densities
      while the areas infested during the three periods the lowest. This might
      represent an attenuation of the risk, because higher densities do not coincide
      with higher infestation. From the point of view of the vector the risk of
      transmission would concentrate between January and March and occupy 50% of the
      city surface in the periphery.

PMID- 15239538
TI  - Hypothesis: an alternative pathway for the regulation of inflammation.
AB  - Regulation of inflammation is a crucial event since its alteration, such as in
      sepsis and chronic autoimmune (i.e. rheumatoid arthritis, lupus erythematosus) or
      infectious diseases (i.e. tuberculosis, leprosy), determines severe tissue
      damage. Although there is a general consensus that regulation of inflammation
      results from a balance between proinflammatory and antiinflammatory pathways, we
      arrived at the conclusion that well known chemoattractants/proinflammatory
      molecules such as bacterial formyl peptides or immune complexes (IC), could
      induce, paradoxically, strong antiinflammatory effects. Thus, we demonstrated
      that N-formyl-methionyl-leucyl-phenylalanine (FMLP) exerted a drastic
      antiinflammatory effect, inhibiting the secretion of tumor necrosis alpha (TNF
      alpha) induced by lipopolysaccharides, a potent TNF-alpha inducer. We also
      determined that in human neutrophils FMLP and IC induced the downregulation of
      receptors for the Fc portion of IgG (FcgammaRII and FcgammaRIIIB). Moreover, FMLP
      inhibited interferon gamma (IFN-gamma)-induced FcgammaRI expression and IC
      downregulate class II molecules of the major histocompatibility complex on
      monocytes. Part of these effects were mediated by the release of aspartic-, serin
      , or metalloproteases. All these results favor the postulation of a new concept
      on the regulation of inflammation carried out through an alternative and non
      conventional pathway, in which a chemoattractant/proinflammatory agent could,
      under certain circumstances, act as an antiinflammatory molecule.

PMID- 15239539
TI  - [Double conventional doses of streptokinase in a massive pulmonary
      thromboembolism with a free-floating thrombus in the right atrium].
AB  - We present a case of severe thromboembolism, with right ventricular dysfunction,
      high vasoactive drug requirements, sustained shock and a free-floating thrombus
      in right atrium. Hemodynamic and clinical picture as well as the
      echocardiographic image were solved after intravenous infusions of two complete
      doses of streptokinase, separated by an interval of 72 hours.

PMID- 15239540
TI  - [Low grade oligodendroglioma in a patient with AIDS].

PMID- 15239541
TI  - [Periorbitary purpura in amiloidosis].

PMID- 15239542
TI  - [Community-acquired pneumonia and multiorganic failure; systemic lupus
      erythematosus?].

PMID- 15239543
TI  - [Acute respiratory distress syndrome. Role of steroids].
AB  - The acute respiratory distress syndrome (ARDS) represents 7.7% of the intensive
      care population, and is associated with great morbidity and mortality (58%).
      Frequently, the mortality can be attributed to more than one cause. Refractory
      hypoxemia is uncommon (15%) and most of the patients also have multiple organic
      dysfunction, sepsis or septic shock. Although there are many publications
      concerning series of cases and clinical trials using steroids as a part of the
      treatment of ARDS, this issue remains controversial. In this article the role of
      steroids in the ARDS is evaluated by analysis of the available literature. We
      conclude that steroids are useful in a subgroup of patients with unresolving
      ARDS, after ruling out an active infection or after treatment with antibiotics.

PMID- 15239544
TI  - [Neuroendocrine aspects of obesity].
AB  - Genetic, social, metabolic, endocrine and neural events participate in the
      physiopathological development of obesity. Because of the multifactorial
      background of obesity, up to now, it has been very difficult to fully understand
      the whole disease. In fact, the relationship between several signals, through
      very complex mechanisms, is only partially known. Obesity, from a neuroendocrine
      point of view, implies taking into account abnormalities in both hypothalamic and
      endocrine functions. Among altered functions in obesity, namely those involving
      the hypothalamo-pituitary-adrenal and adipo-insular axes activities and the
      neural circuitry controlling food intake and energy expenditure have been
      subjects of major research. This review attempts to update information about this
      disorder by, firstly, analyzing each of the already mentioned systems and,
      secondly, focusing on the normal function of integrated processes. Finally, the
      discussion of some altered mechanisms and the role played by each of them in the
      development/maintenance of the obesity phenotype are also revisited.

PMID- 15239545
TI  - [From Fabiola to Fliedner and the first school of nurses].

PMID- 15239546
TI  - [Explained quotations. On fame: Morgagni, Linneo, and others].

PMID- 15239547
TI  - [Squid's giant axon].

PMID- 15239548
TI  - [Bivalent role of the immune system in tumor growth].

PMID- 15239549
TI  - [The heterozygote advantage].

PMID- 15239551
TI  - Current concepts and issues in blood management.
AB  - Blood management in orthopedic surgery is no longer an option; it is a
      requirement. The combination of patient desire to avoid transfusion, increasing
      evidence of multiple risks, decreasing blood supplies, and increasing costs
      mandate attention. This article addresses the balance of risk versus benefit in
      blood transfusion and presents a perioperative plan of blood management for
      patients undergoing orthopedic surgery.

PMID- 15239552
TI  - Aprotinin: a pharmacologic overview.
AB  - Aprotinin is a polypeptide with serine protease inhibitory activity of key
      enzymes associated with inflammatory, fibrinolytic, and hemostatic pathways. The
      drug binds directly to the fibrinolytic plasmin at the lower plasmin-inhibiting
      dose (plasma concentration, 137 KIU/mL), and the inflammatory mediator,
      kallikrein, using the higher kallikrein-inhibiting dose (plasma concentration,
      >250 KIU/mL). Aprotinin inhibits platelet glycoprotein loss (GpIb and GpIIb/IIIa
      receptors) associated with cardiopulmonary bypass and has been described as
      platelet sparing. Current literature supports direct anti-inflammatory effects
      through modulation of neutrophil activation, attachment, and transmigration, with
      resultant blunting in the rise of proinflammatory cytokine levels and deleterious
      tissue damaging enzymes. The pharmacologic properties of aprotinin may lead
      clinicians to consider this therapy for use as a hemostatic and anti-inflammatory
      agent in surgeries beyond its established use in coronary artery bypass graft
      surgery.

PMID- 15239553
TI  - Efficacy and safety of aprotinin in cardiac surgery.
AB  - Cardiac surgery and cardiopulmonary bypass produces bleeding and the need for
      allogenic blood product transfusions in many patients. Blood conservation is
      important in the perioperative management of patients. Aprotinin, a serine
      protease inhibitor isolated from bovine lung, is a complex protease inhibitor
      that is an antifibrinolytic, inhibits contact activation, and decreases the
      inflammatory response to cardiopulmonary bypass. Aprotinin reduces blood loss and
      transfusion requirements in adult and pediatric patients undergoing cardiac
      surgery with cardiopulmonary bypass. Full-dose aprotinin significantly reduces
      postoperative blood loss and has been demonstrated in multiple prospective
      blinded studies to be safe and effective. One of the major adverse effects is
      anaphylaxis that occurs on re-exposure to aprotinin.

PMID- 15239554
TI  - Intraoperative blood management in joint replacement surgery.
AB  - Interest is growing in blood conservation and avoidance of transfusion in
      patients undergoing orthopedic surgery, especially in the field of joint
      replacement. Several methods have proven successful in reducing intraoperative
      blood loss, which can translate into lessened allogeneic and autologous
      transfusion requirements. Available techniques include acute normovolemic
      hemodilution, hypotensive anesthesia, intraoperative blood salvage, specialized
      cautery, topical hemostatic agents, and pharmacologic agents given in the
      perioperative period. The greatest potential benefit arises in operations with
      greater expected blood loss or in special situations such as in patients with
      religious issues, bilateral joint replacement, coagulation disorders, or
      significant preoperative anemia.

PMID- 15239555
TI  - Blood management in patients with deep prosthetic hip and knee infections.
AB  - Patients undergoing treatment for infected hip and knee replacements often have
      significant blood loss and require allogeneic blood transfusions. In the setting
      of sepsis, traditional methods of blood management such as preoperative blood
      donations, cell savers, and reinfusion drains are contraindicated. Pharmacologic
      agents can minimize transfusion requirements by increasing erythropoiesis, or
      minimize perioperative blood loss. This article reviews the use of these agents
      in the management of patients with deep prosthetic hip and knee infections.

PMID- 15239556
TI  - A direct antifibrinolytic agent in major orthopedic surgery.
AB  - Aprotinin is a potent pharmacological agent that reduces bleeding. In current
      surgical practices, the rate of blood transfusions has decreased with the use of
      aprotinin. Recently, studies using aprotinin have been conducted in orthopedic
      surgery. Several trials have been performed in patients undergoing total hip
      replacement and total knee replacement. Aprotinin moderately decreased blood loss
      in these patients. When aprotinin was used in patients with a high-risk of
      bleeding (ie, patients with cancer, sepsis, or undergoing reoperation), potent
      hemostatic activity occurred and the rate of blood transfusions significantly
      decreased. No increase in deep vein thrombosis and pulmonary embolism was
      observed. One adverse effect was the potential occurrence of an anaphylactoid
      reaction. Prophylactic administration of aprotinin should be considered in
      extensive spine surgery and in high-risk orthopedic operations. The decision to
      use aprotinin can be guided by a risk/benefit analysis.

PMID- 15239557
TI  - Aprotinin in spine surgery: review of the literature.
AB  - Based on a literature review, this article evaluates the efficacy of aprotinin to
      limit blood transfusion during spine surgery. Most prospective studies confirm
      this effect. However, broader studies are required to evaluate adverse effects.
      Severe complications are rarely, if ever, reported. Given the small size of most
      samples, complications are expected because of the widespread use of the drug.
      The cost of the medication has to be balanced with the cost of blood transfusion.
      A careful use of aprotinin allows a surgeon dealing with high-risk patients to
      avoid or limit the use of transfusions. For patients who are not high-risk,
      aprotinin should be avoided until other questions are answered.

PMID- 15239558
TI  - [The impact of prolactinoma in human reproduction].
AB  - AIMS: Prolactinomas represent a 60% of pituitary tumors with various symptoms,
      hormonal and reproductive abnormalities. OBJECTIVE: Assessment of epidemiology of
      prolactinomas in our hospital. PATIENTS AND METHOD: We reviewed the clinical
      charts of 32 patients seen throughout 1991-2001. RESULTS: Twenty seven patients
      (84%) were females and 5 (16%) males. Average age was 30.3 +/- SD 11.3 years with
      a range of 6 to 58 years. Menstrual irregularities was the most frequent finding
      in patients with micro and macroadenoma; infertility was seen in 4 (33%) patients
      with pituitary microadenoma and 2 (10%) with macroadenoma. A patient with
      macroadenoma had delayed puberty and another with microadenoma isosexual
      precocious puberty. All cases showed hyperprolactinemia (microadenomas x 94.5 +/-
      SD 96.4 ng/mL; macroadenomas x 108.8 +/- SD 79.4 ng/mL). Hypothyroidism and
      hypogonadal hypogonadotropism were the most common associated diagnoses before an
      after treatment for both groups. Radiologic presence of microadenoma was observed
      in 12 (38%) patients and in 20 (26%) with macroadenoma. Bitemporal hemianopsia
      was the most common finding during visual field evaluation (28% microadenoma, 44%
      macroadenoma). Pharmacologic treatment with bromocriptine (2.5 - 7.5 mg)
      prevailed and showed a major impact upon symptoms improvement and significant
      decrease of serum prolactin levels (p < 0.05). Only five patients out of 20 who
      underwent surgery developed transient diabetes insipidus. Tumor relapse was
      observed in 10 (63%) of 16 patients with macroadenomas that required surgery.
      CONCLUSIONS: In our study prolactinomas prevailed among females in reproductive
      age with a higher incidence of macroadenomas. The most common alterations related
      to reproductive tract were menstrual irregularities, galactorrhea, infertility,
      hyperprolactinemia, hypogonadism and hypothyroidism. Abnormalities of puberty
      were also seen. Treatment with dopaminergic agonists (bromocriptine) was highly
      effective to decrease prolactin circulating levels.

PMID- 15239559
TI  - [Hormonal replacement therapy and breast cancer. A case-control study].
AB  - AIMS: Breast cancer is the second more frequently neoplasia in the woman and the
      first cause of mortality after 35 years old. It is considered a multifactorial
      illness, since is influenced for genetic, dietary and endocrine factors. Among
      these, hormonal replacement therapy (HRT) have been assigned benefits effect, as
      well as risks to increase the breast cancer incidence, because presence of
      estrogens receptor in the neoplasia cells makes think that the estrogens and
      other sexual hormones constitute a factor promoter of this cancer. OBJECTIVE: The
      objective of this study was to determine the association of HRT as risk factor in
      the incidence of breast cancer, in women from oncology-gynecological service.
      PATIENTS AND METHOD: Was carried out this descriptive study in patients that used
      HRT, considering as cases patients with breast cancer confirmed by
      hystophatological study and controls the patients without breast cancer. To
      statistical analysis took mean occurrence using the momios reason (MM), with
      confidence interval of 95% (CI), and chi2 test of Mantel-Haenszel, for a
      significant value of p < 0.05. RESULTS: Were included successively 250 patients,
      in 100 of these were confirmed diagnosis of breast cancer, 60 patients (37.5%)
      used HRT with mean of 3 years and 40 patients (44.4%) did not use HRT (Cases),
      the other 150 patients did not have breast cancer, 100 of these used HRT and 50
      patients did not use HRT (Control). The statistical analysis showed that the HRT
      had a MM 0.75 (IC 95% 0.62-1.15) p=0.28, the maternal nursing with MM 0.68 (IC
      95% 0.59-1.08) p=0.05, the multiparity with MM 0.42 (IC 95% 0.16-1.87) p=0.26,
      obesity MM 1.67 (IC 95% 0.99-1.54) p=0.05, familial history with MM 1.23 (IC 95%
      0.83-1.54) p=0.05. CONCLUSIONS: These results show that does not exist a direct
      association between HRT and breast cancer. Therefore, whenever takes the decision
      to use the HRT should be considered the possible risks and benefits
      individualizing the patient, also the mammography should be present in mind, same
      that frequent physical examination, autoexploration and the use of HRT smaller to
      5 years.

PMID- 15239561
TI  - [Urinary calcium and bone turnover markers].
AB  - OBJECTIVE: To know the relationship between bone turnover markers and urinary
      calcium excretion with and without oral calcium load in postmenopausal and young
      women. PATIENTS AND METHOD: A cross-sectional study in 100 women (50 with normal
      menstrual cycle and 50 postmenopausal). After 5 days with a specific diet, urine
      of 24 hours, 2 hours in fasting, and 4 hours after oral calcium load was
      collected (the last urine collection was only done in 20 patients in each group.
      In these patients, an x-ray absorptiometry of distal forearm and vitamin D levels
      were evaluated too). Calcium, alkaline phosphatase, calcitonin, parathormone, N
      telopeptides of type I collagen, and osteocalcin serum levels were measured in
      fasting. Creatinine and calcium were measured in urine to obtain the Ca/cr index.
      RESULTS: Postmenopausal women had lower calcitonin levels while the Ca/cr index
      of 2 hours in fasting was higher than the eumenoreic women. We found significant
      correlation between Ca/cr index of 2 hours with age (R = .21; p = .04),
      parathormone (R = .21; p = .04), and calcitonin levels (R = -.29; p = .005).
      There was not correlation with the urinary calcium excretion including the 4 hour
      postload collection with the biochemical markers of bone turnover or mineral bone
      density of distal forearm. CONCLUSIONS: The urinary Ca/Cr index of 2 hours in
      fasting is related to parathormone levels and has a negative relationship with
      calcitonin levels in postmenopausal women. However, the urinary calcium excretion
      after oral calcium load was not related with the bone turnover grade.

PMID- 15239560
TI  - [Effects of the hormone replacement therapy on cardiovascular system, bone mass
      and memory in climacteric patients].
AB  - OBJECTIVE: To evaluate the effect of the hormone replacement therapy type
      estradiol-medroxyprogesterone and tibolona on cardiovascular system, bone mass
      and memory in the climacteric patients. PATIENTS AND METHOD: From January through
      December 2001 at the Specialties Hospital No. 1, we included 77 consecutive
      climacteric patients. They were divided in 2 groups: premenopause in treatment
      with estradiol-medroxyprogesterone and postmenopause with tibolona. We studied
      cardiovascular system, the bone mass and memory. The statistical analysis was by
      means of t Student for difference between the groups. RESULTS: With the estradiol
      medroxyprogesterone use, the blood pressure diminished significaticantly just for
      systolic pressure (-10.22/-6.38 mmHg). Cholesterol and triglyceride, both
      diminished significantly (-43.92 mg and -58.79 mg). There is not significance for
      the bone mass of lumbar-spine and femoral neck (+0.68% and +0.69%) as neither in
      the memory test (20-22). With the tibolona use, the blood pressure was not
      reduced significantly (-6.93/-1.94 mmHg), with single significant reduction for
      cholesterol (-25.83 mg and -18.15 mg), presenting bone mass significant
      improvement just for femoral neck (+0.13% and +0.84%) and without improving in
      the memory test (17-18). CONCLUSIONS: A diminution of lipids with the estradiol
      medroxyprogesterone use, as well as reduction of the cholesterol and improvement
      of the bone mass with the tibolona use but without benefits in the memory test
      with both treatments.

PMID- 15239562
TI  - [Current perspectives in cervical cancer].
AB  - Cervical cancer is a Public Health problem among women worldwide, especially in
      the developing world. The understanding of the HPV association with the high
      grade squamous intraepithelial lesions and cervical cancer and the knowledge of
      the pre-invasive lesions natural history have strengthened the justification of
      different means of cancer prevention and screening programs, the application of
      different pre-invasive lesion treatments and particularly advances in
      conventional treatments of cervical cancer. In the last thirty years, cervical
      cancer's incidence and mortality rates have decreased in more than 75% in
      developed nations due to efficient application of secondary prevention based on
      cytology and colposcopy screening programs plus to in-office implementation of
      precursor lesions treatment methods. In the developing nations, these
      achievements can be obtained using specific steps of primary prevention, massive
      participation of risk patients in screening programs and improving ambulatory
      application of pre-invasive cervical lesion treatments. In Mexico several
      indicators suggest that this condition has began. New knowledge paradigms of the
      local immune response to HPV-cervical cancer pre-invasive and invasive lesions
      are being added to the construction of new preventive and therapeutic anti-cancer
      strategies. The preventive vaccines anti-high risk oncogenic-HPVs offer a good
      perspective in short term, also the use of different cellular immunotherapy
      strategies anti-cervical cancer as adyuvant of conventional treatments offer an
      encouraging panorama in not long term. In the next years, the improving of
      specific genes determination and their correlation with biologic features of the
      specific tumor which are involved on pre-invasive and invasive stages of cervical
      cancer will raise the understanding and the treatment of these patients.

PMID- 15239563
TI  - [Ureteral obstruction: an unfrequent complication of Burch colposuspension.
      Report of two cases].
AB  - The injury of the urinary tract in a pelvic surgery is inherent, its real
      frequency in which it presents, is difficult to establish, due that not all the
      lesions are published. In this article, two cases of ureteral obstruction
      posterior to a Burch-procedure, and the way they were resolved is reported. The
      ureteral obstruction is a very rare complication, but one that has the worst and
      severe medico-legal consequences, if they are not resolved opportunely. Its
      frequency in our service was of 0.41%, in 240 Burch-procedures that were realized
      during April of 1997 and June of 2000.

PMID- 15239564
TI  - [Tubal pregnancy treated with oral methotrexate. Report of one case].
AB  - Report of a case of ectopic pregnancy, treated with oral methotrexate qd. as
      medical management of tubal pregnancy. We report a succesfully case.

PMID- 15239565
TI  - A flexible digit with tactile feedback for invasive clinical applications.
AB  - This paper describes research on measurement of tactile sense using a flexible
      digit appropriate to endoscopy and minimal access surgery. It is envisaged that
      the sensing method will facilitate the navigation of flexible invasive devices,
      such as endoscopes, and also aid diagnosis using tactile perception as well as
      visual observation. The proposed master-slave digit system incorporates the
      application of the distributive sensing method applied to tactile sensing in
      order to discriminate different contact conditions of the flexible digit. The
      paper concentrates on the description of the application of this method and
      places this in the context of the user and the integrated system. The approach to
      sensing is able to discriminate the position, magnitude, distributed profile and
      width of the applied contacting load by using only four sensing points. Values to
      describe these parameters are evaluated to an accuracy greater than 93 per cent.

PMID- 15239566
TI  - Modelling the bioelectric behaviour of halo pin-patient structures during
      magnetic resonance imaging.
AB  - Bioelectric compatibility of electrically conductive halo fixation devices and
      magnetic resonance (MR) imaging has been largely based on resulting image
      quality. Previous studies have focused primarily on improving image quality and,
      although the electrical characteristics of the system during imaging may have
      been noted, they have not been studied in depth. Utilizing both a theoretical and
      experimental approximation, this study focuses on the bioelectric characteristics
      of the pin-patient structures typically enountered in clinical halo fixation
      systems. Results indicate that the halo pin-patient system can be modelled using
      a resistor-inductor-capacitor circuit and that simple attempts at improving
      compatibility through increasing interface resistance by the use of insulated
      pins may not be an effective approach to improving halo instrumentation
      compatibility with new, stronger magnetic and higher-frequency resonance imaging
      systems.

PMID- 15239567
TI  - Propagation of fatigue cracks in acrylic bone cements containing different
      radiopaque agents.
AB  - In this work three iodine-containing monomers were proposed as new radiopaque
      agents for acrylic bone cements. In previous studies the addition of iodine
      containing methacrylate monomers provided a statistically significant increase in
      tensile stress, fracture toughness and ductility, with respect to the barium
      sulphate (BaSO4)-containing cement. However, since fatigue resistance is one of
      the main properties required to ensure a good long-term performance of permanent
      prostheses, it is important to compare the fatigue properties of these new bone
      cement formulations with the radiolucent and BaSO4-containing bone cements.
      Because the acrylic cements have initial cracks, fatigue crack propagation
      studies were performed. It can be observed that these acrylic cements followed
      the Paris-Erdogan model. The results showed that the addition of some organic
      radiopacifiers (DISMA, TIBMA) increased the fatigue crack propagation resistance
      as compared to the radiolucent cement, being similar to the BaSO4-containing
      cement. The radiolucent cement showed a low crack propagation resistance.

PMID- 15239568
TI  - Modelling the effect of prosthetic feet and shoes on the heel-ground contact
      force in amputee gait.
AB  - Gait laboratory measurements have been widely used to explore footwear and
      prosthetic effects on intact and amputee gait in spite of the confounding effects
      of adaptation, acclimation and inherent variability of human subjects. To
      facilitate understanding of the variables that affect impact forces that arise
      from heel-ground contact during amputee walking, a lumped parameter model is
      proposed to simulate the movement of the human body, prosthetic components and
      footwear during the period immediately following initial contact. Non-linear
      viscoelastic properties of prosthetic feet have a proportional relationship to
      both the magnitude of the impact peak and the rate of increase in the ground
      reaction force (GRF) immediately following initial contact. Footwear, in spite of
      a larger capacity to dissipate impact energy than a prosthetic foot alone, can
      actually amplify the magnitude of the impact peak. These results suggest
      limitations in the ability of conventional prosthetic feet and footwear to
      attenuate transmission of potential tissue-damaging forces.

PMID- 15239569
TI  - Prediction of inter-segment stability and osteophyte formation on the multi
      segment C2-C7 after unilateral and bilateral facetectomy.
AB  - The objective of this study was to determine the intersegment stability, disc
      degeneration, and osteophytes formation on the multisegment cervical spine (C2
      C7) after unilateral and bilateral facetectomy. A geometrically accurate non
      linear three-dimensional model of the intact human cervical spine was created
      from the digitized coordinates of the dry vertebrae. The intact model was
      validated against the published results under physiological loading conditions.
      Eight surgically altered models were created from the intact model. The intact
      and surgical altered models were subjected to physiological loading. The
      inclusion of five levels in the present model allowed accurate determination of
      the intersegment responses and internal cortical bone and disc annulus stress in
      the adjacent spinal components. Results indicated that facetectomy performed on
      C5-C6 significantly affects the corresponding stress and intersegment motions at
      the corresponding C5-C6 levels. The maximum increases were 18 per cent for
      bilateral facetectomy and 7 per cent for unilateral facetectomy under lateral
      bending. Combined flexion-extension and axial rotation caused an approximately
      similar amount of increases after total facetectomy. In addition, adjacent
      segments (C4-C5 and C6-7) also experience a slight increase in the intersegment
      responses and internal stress after facetectomy. It has been shown that
      facetectomy of greater than 50 per cent resulted in segment hypermobility and
      substantial increase in the disc annulus and cortical bone stress. Increase in
      the stress may lead to osteophytes formation. This study revealed important
      information that will help clinicians identify the critical intersegment
      stability and to decide on the amount of facets resection.

PMID- 15239570
TI  - Frictional resistance characteristics of a capsule inside the intestine for
      microendoscope design.
AB  - The design of the capsule body for a self-propelled endoscope is important from
      the frictional resistance point of view. The motivation of this work was to gain
      a better understanding of the effect of capsule shape on the frictional
      resistance of the capsule inside a small intestine. Special experimental set-ups
      were built to investigate the frictional resistance of the capsule and the
      viscoelastic deformation characteristics of the small intestine specimen of a
      pig. Tests were performed with capsules of various shapes and dimensions.
      Experimental data showed that a smooth cylindrical capsule geometry resulted in
      the least frictional resistance due to the shape and relatively small surface
      area. Also, it was found that the variation of frictional resistance of the
      capsule was closely related to the local change in the viscoelastic property of
      the intestine due to the heterogeneity of the internal structure of the
      intestine.

PMID- 15239571
TI  - Strain rate effect on the failure properties of tendons.
AB  - The purpose of this study is to evaluate the effect of strain rate on the failure
      properties of tendons. Seventy-five chicken flexor digitorum profundus (FDP)
      tendons were tensile tested at 15 strain rates, ranging from 0.05 to 150 per
      cent/s. Results showed that strain rate had little effect on the shape of the
      stress-strain curve. No significant change was observed in the toe region, while
      the slope of the linear region increased with the increase in strain rate.
      Generally, the ultimate tensile strength (UTS) and elastic modulus increased
      significantly as strain rate increased (p < 0.01), while no significant change in
      strain at UTS (p > 0.01) was observed. It was found the change in failure
      properties of tendons was not significant, with small change in strain rate.

PMID- 15239572
TI  - How should we amend the Human Tissue Act 1961?

PMID- 15239573
TI  - Human tissue retention.

PMID- 15239574
TI  - Geographical profiling of criminals.

PMID- 15239575
TI  - The use and abuse of human tissue: an analysis of the ethical issues raised by
      the proposed Human Tissue Act.

PMID- 15239576
TI  - Inadequate proof reading.

PMID- 15239577
TI  - Make health and safety a priority.

PMID- 15239578
TI  - Current and future employment trends within the dental profession.

PMID- 15239579
TI  - Update on waste management for the practice of dentistry.

PMID- 15239580
TI  - Legal aspects of oral radiology.

PMID- 15239581
TI  - Coping with the unexpected.

PMID- 15239582
TI  - Health and safety aspects of dental restorative materials.

PMID- 15239583
TI  - Sterilisation and disinfection in dental practice.

PMID- 15239584
TI  - Dental practice safety--an inspector's viewpoint.

PMID- 15239585
TI  - Old bugs and new: classical and emerging pathogens--relevance to dental practice.

PMID- 15239586
TI  - Update on steam sterilisation and bench-top sterilisers (autoclaves).

PMID- 15239587
TI  - Licensing of dental X-ray equipment.

PMID- 15239588
TI  - Participation of caudal ventrolateral medulla in the regulation of gallbladder
      motility in rabbits.
AB  - To investigate whether the caudal ventrolateral medulla (CVLM) participates in
      the regulation of gallbladder motility, we studied the effects of microinjection
      of L-glutamate and other agents into the CVLM on gallbladder pressure (GP) in
      anesthetized rabbits. A frog bladder connected with a force transducer was
      inserted into the gallbladder to record the change of GP. Microinjection of L
      glutamate into the CVLM decreased GP, While micnoinjection of gamma-amino-butyric
      acid (GABA) increased GP. Microinjection of ketamine, a noncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist, into CVLM increased GP, while
      microinjection of 6-cyano-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX), a
      competitive (+/-)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA)/kainate receptor antagonist, had no significant effect on GP. The effects
      of L-glutamate was abolished by ketamine, but not by CNQX. Intravenous injection
      of phentolamine or transection of the spinal cord eliminated the effects of L
      glutamate on GP. These results indicate that [1] CVLM participated in the
      regulation of gallbladder motility; [2] endogenous L-glutamate in CVLM is
      involved in the regulation mediated by NMDA receptors, the output of which is
      sent through sympathetic nerve and alpha-adrenergic receptors.

PMID- 15239589
TI  - Effects of age on plasma levels of calcium-regulating hormones and bone status in
      male SAMP8 mice.
AB  - This study was undertaken to examine whether the plasma levels of calcium
      regulating hormones and bone status alter with age in male senescence accelerated
      mice (SAM), SAMP8. Age-matched senescence-resistant mice, SAMR1, were used as
      controls. The blood and femur samples were collected at 2.5 months of age (M) and
      then monthly from 3 to 12 M for physicochemical analyses, biochemical analyses,
      and the determination of hormones by radioimmunoassay. With advancing age, the
      plasma calcitonin (CT) levels decreased progressively, and the plasma parathyroid
      hormone (PTH) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3) levels increased in
      both SAMR1 and SAMP8. The plasma calcium concentrations were maintained within a
      narrow range throughout the experimental period, while the plasma phosphorus (P)
      concentrations decreased with age in both strains. In contrast to SAMR1, the
      curves of age-related changes in the plasma CT levels and P concentrations were
      lower, and those in the plasma PTH levels were higher in SAMP8. The femoral bone
      densities and calcium contents increased gradually with age from the beginning of
      the experiment and peaked at 6 M in both strains, then declined. Those peaks were
      lower in SAMP8 than in SAMR1. These results indicate that the male SAMP8 develops
      osteoporotic signs earlier than SAMR1, and is proved to be a satisfactory animal
      model for longitudinal studies related to osteoporosis for men.

PMID- 15239590
TI  - Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics
      with the use of Microsoft Excel spreadsheets.
AB  - The purpose of this study was to develop a method to simulate the cardiac action
      potential using a Microsoft Excel spreadsheet. The mathematical model contained
      voltage-gated ionic currents that were modeled using either Beeler-Reuter (B-R)
      or Luo-Rudy (L-R) phase 1 kinetics. The simulation protocol involves the use of
      in-cell formulas directly typed into a spreadsheet. The capability of spreadsheet
      iteration was used in these simulations. It does not require any prior knowledge
      of computer programming, although the use of the macro language can speed up the
      calculation. The normal configuration of the cardiac ventricular action potential
      can be well simulated in the B-R model that is defined by four individual ionic
      currents, each representing the diffusion of ions through channels in the
      membrane. The contribution of Na+ inward current to the rate of depolarization is
      reproduced in this model. After removal of Na+ current from the model, a constant
      current stimulus elicits an oscillatory change in membrane potential. In the L-R
      phase 1 model where six types of ionic currents were defined, the effect of
      extracellular K+ concentration on changes both in the time course of
      repolarization and in the time-independent K+ current can be demonstrated, when
      the solutions are implemented in Excel. Using the simulation protocols described
      here, the users can readily study and graphically display the underlying
      properties of ionic currents to see how changes in these properties determine the
      behavior of the heart cell. The method employed in these simulation protocols may
      also be extended or modified to other biological simulation programs.

PMID- 15239591
TI  - Cycloheximide enhances maintenance of methamphetamine-induced conditioned place
      preference.
AB  - Accrued evidence demonstrated the necessity of protein synthesis at acquisition,
      consolidation and expression stages in conditioning/learning tasks, while the
      underlying mechanisms of the maintenance of memory remained less explored. This
      study was designed to characterize the maintenance of methamphetamine-induced
      conditioned place preference, a drug-induced learning and memory. In addition,
      cycloheximide, a protein synthesis inhibitor, was used to examine the involvement
      of protein synthesis in the maintenance of such place preference memory. We found
      that the maintenance of the rapidly-established methamphetamine (2 mg/kg, i.p.) 
      induced conditioned place preference could be long-lasting and even over fifty
      days under the present protocol of extinction. Moreover, it was of interest to
      note the undulating expression of this conditioned place preference throughout
      the extinction protocol. Most importantly, as the methamphetamine-induced
      conditioned place preference was acquired and expressed by mice, the saline
      pretreated control mice underwent numbers of intermittent extinction across a
      long-term retention test period, while cycloheximide-pretreated mice exhibited
      unaltered methamphetamine-induced conditioned place preference throughout the
      same retention test period. Taken together, we conclude that [1] methamphetamine
      induced conditioned place preference could last for a long period of time, and
      such place preference memory is reluctant to extinguish even animals' repeated
      exposure to the previous conditioned environment at a drug-free status, and [2]
      blockade of protein synthesis may enhance the maintenance of the methamphetamine
      induced conditioned place preference.

PMID- 15239592
TI  - Cardiopulmonary response to vasopressin-induced activation on V1A receptors in
      the lateral ventrolateral medulla in the rat.
AB  - The aim of the study was to examine whether or not arginine vasopressin (AVP)
      might modulate cardiopulmonary functions by acting on the lateral area of the
      ventrolateral medulla (VLM) in the rat. The rat was anesthetized, bilaterally
      vagotomized, paralyzed, ventilated, and then placed on a stereotaxic instrument
      in a prone position. Activity of the phrenic nerve (PNA) was monitored at
      normocapnia and hypercapnia in hyperoxia. Microinjection of AVP into the lateral
      region of the VLM resulted in a brief apnea followed by a significant decrease in
      PNA amplitude and a concomitant significant increase in blood pressure. The
      inhibition of PNA with AVP treatment could be partly attenuated by hypercapnia
      but not by phentolamine. Both inhibition of PNA and pressor response with AVP
      microinjection into the lateral VLM were totally abolished after pretreatment
      with AVP V1A receptor antagonist. These results suggest that a vasopressinergic
      pathway projects to the lateral VLM and modulates cardiopulmonary functions via
      AVP V1A receptors on neurons within the lateral VLM.

PMID- 15239593
TI  - Evaluation of mouse blastocyst implantation rate by morphology grading.
AB  - The aim of our study is to observe the relationship between the blastocyst
      morphology and the implantation rate for mice. Mouse embryos obtained from the
      superovulated-ICR mice were cultured in vitro from 1-cell zygotes to blastocysts.
      Mouse blastocysts were then classified into 3 grades: grade I, small blastocysts;
      grade II, large blastocysts; grade III, hatching blastocysts. They were
      independently transferred into the uterus of recipient females mated with
      vasectomized male mice on 96 hours after the zygotes were cultured in vitro. The
      successful implantation was checked by injection of Chicago Sky Blue 6B on the
      second day after embryo transfer. Although there was no significant difference in
      the implantation rates between the grade III and grade II, grade I was
      significantly decreased, as compared with grade III. Grade I and grade II was
      also significantly decreased in both the diameter of blastocysts and cell number
      of inner cell mass (ICM) and trophectoderm (TE), as compared with grade III.
      These findings indicate that the expanded and hatching blastocyst selections for
      embryo transfer in in vitro fertilization were evaluated with the high
      implantation rate.

PMID- 15239594
TI  - Pre- and post-training infusion of prazosin into the bed nucleus of the stria
      terminalis impaired acquisition and retention in a Morris water maze task.
AB  - The bed nucleus of the stria terminalis (BNST) is interconnected with the
      amygdala that is implicated in memory modulation. In view of the innervation of
      this structure by the hippocampus and brain stem noradrenergic nuclei, this study
      examined the role of BNST noradrenergic activity in acquisition, formation and
      expression of spatial memory. Male Wistar rats with indwelling cannulae in the
      BNST were trained on a spatial navigation task in the Morris water maze. Groups
      of rats received intra-BNST infusion of vehicle, norepinephrine, prazosin or both
      drugs shortly before or after each daily training session, or shortly before
      retention tests. Results showed that pre- or posttraining infusion of 1.0 microg
      prazosin impaired acquisition and retention, but the treatment had no effect on a
      cued response task. Posttraining infusion of 1.0 microg norepinephrine enhanced
      acquisition and retention, and this enhancing effect was blocked by simultaneous
      infusion of 0.3 microg prazosin. Pretest intra-BNST of prazosin or norepinephrine
      at a dose of 1.0 microg did not impair expression of the spatial navigation
      memory. These findings suggest that the BNST noradrengergic function is involved
      in modulating acquisition and formation of spatial memory that engage the
      hippocampus.

PMID- 15239595
TI  - [Yellow fever and its control].

PMID- 15239596
TI  - [The 'bull's eye' pattern in hepatic tomography].
AB  - Invasive fungal infections are more commonly found in patients who develop
      neutropenia after chemotherapy. A 4-year-old girl with diagnosis of acute
      lymphoid leukemia developed febrile neutropenia after chemotherapy. Broad
      spectrum antibiotics and antimycotic therapy were initiated. Candida albicans was
      isolated and Entamoeba histolytica was observed in stool examination. Chronic
      disseminated candidiasis had developed and was treated with amphotericin B,
      initially, and fluconazol. Computed tomography images were obtained that
      demonstrated a classic 'bull's eye' pattern; a concurrent histological study
      confirmed the diagnosis. Candida spp. is the major cause of opportunistic mycosis
      in immunosuppresed patients receiving chemotherapy for haematologic malignancies.
      An initial infection results in disseminated candidiasis, which persists and
      becomes chronic. In the 4-year-old patient, the identified risk factors consisted
      of a previous therapy with broad spectrum antibiotics, the gastrointestinal tract
      colonization with Candida albicans and prolonged neutropenia. Imaging diagnoses
      are made by ultrasonography, computed tomography and magnetic resonance. With
      ultrasound and tomography, 4 distinct patterns have been described. Pattern 1
      ('wheels within wheels') and 2 ('bull's eye') are important, since they are
      characteristic of chronic disseminated candidiasis. The third pattern (hypoechoic
      image) is the most common finding with both techniques. In the current patient,
      patterns 2 and 3 were seen and the diagnosis was confirmed by histological study.

PMID- 15239597
TI  - [Absence of asymptomatic malaria in schoolchildren of Quibdo, Choco].
AB  - Asymptomatic malaria is characteristic of high intensity transmission areas in
      Africa but unusual in low transmission areas in Latin America. Nevertheless,
      asymptomatic malaria has been reported to be frequent in areas in Latin America
      with high and moderate intensity of transmission. Asymptomatic malaria can affect
      both individuals who carry parasites and are cryptic carrier reservoirs for the
      community. Individuals chronically infected with malaria parasites are usually
      unidentifiable by most malaria control programmes. In order to identify whether
      asymptomatic individuals harboring malaria parasites are an important reservoir
      of infection in Quibdo, Choco, the prevalence of asymptomatic malaria was
      assessed in schoolchildren. This study was part of a major study of the
      epidemiology of malaria in Quibdo. A total of 255 children from 5 schools were
      examined, of which 223 were included in the analysis. Children reported headache
      (34%), cough (32%), and diarrhoea (9%). None of the children presented a positive
      thick smear. In addition, IFA tests in a subsample of 25 children were negative.
      By these criteria, the prevalence of asymptomatic malaria in Quibdo
      schoolchildren is 0% (95%C.I.: 0.0-1.4). Although asymptomatic malaria in adults
      possibly occurs, a very low prevalence is predicted.

PMID- 15239598
TI  - [Molecular evolution and geographic origins of type 1 human lymphotrophic virus
      in Colombia detected by RFLP polymorphism].
AB  - The human T-lymphotropic virus type I (HTLV-I) infection is a public health
      problem in many endemic areas of Colombia. The subtyping of HTLV-I was based on
      the analysis of restriction fragment length polymorphisms (RFLP) in 3'LTR
      proviral DNA. From 31 HTLV-I isolates collected throughout Colombia, a RFLP
      analysis in a 737 bp 3'LTR fragment was performed. Fifty-eight percent (18/31)
      were identified as the Cosmopolitan subtype a, 19.4% (6/31) in the West African
      subtype b, 12.9% (4/31) in the Cosmopolitan subtype b and 9.6% (3/31) in the West
      African subtype c. The phylogenetic analysis of 3'LTR nucleotide sequences
      indicated that all the isolates in the current study were in the subgroup B or
      Japanese, in contrast with the highly divergent isolates from native Amerindians
      grouped in subgroup a or Transcontinental. The supported hypothesis was that of a
      post-Columbus introduction of virus represented in the African-American
      communities of the Colombian South Pacific. Some viral isolates from Colombian
      native Amerindians exhibited a nucleotide variation compatible with a Paleolithic
      introduction of the virus. The genetic diversity of HTLV-I in Colombia is complex
      and probably represents several independent introductions of lymphotropic virus.

PMID- 15239599
TI  - [Efficacy of ivermectin in the treatment of children parasitized by Strongyloides
      stercoralis].
AB  - In a small village of Amazonian Colombia, the efficacy of ivermectin (200
      microg/kg/day) was determined in a two-day treatment of children with
      uncomplicated strongyloidiasis. Criteria for inclusion in the study were as
      follows: absence of acute disease, no pretreatment with antiparasitic drugs
      within the last month, absence of severe liver or neurological disorders, and at
      least 2 of 4 stool samples positive for Strongyloides stercoralis. The Baermann
      technique was used to detect larvae; it had the advantage of reducing the
      frequency of false negative results in the subsequent examinations. Of 60
      potential subjects, 49 fulfilled the above criteria. The cure rate for the S.
      stercoralis infection was 94% (46/49), with slight and temporary side effects.
      The effects of ivermectin on other intestinal parasites were characterized as
      well. In conclusion, a 200 microg/kg/d ivermectin dose was an adequate
      therapeutic regimen in the treatment of uncomplicated strongyloidiasis in
      children.

PMID- 15239600
TI  - [Toxicological and immunological aspects of scorpion venom (Tytius pachyurus):
      neutralizing capacity of antivenoms produced in Latin America].
AB  - The toxicity and immunochemical properties of Tityus pachyurus Pocock scorpion
      venom was characterized, as well as the neutralization capacity against it by
      three anti-scorpion antivenoms (Alacramyn, Instituto Bioclon, Mexico; Suero
      antiescorpionico, Instituto Butantan, Sao Paulo, Brasil; and Suero
      antiescorpionico, Centro de Biotecnologia, Universidad Central de Venezuela,
      Caracas, Venezuela). The venom yield, obtained by manual milking, 680+/-20 microg
      venom, a 50% lethal dose in mice was 4.8 microg/kg (90 microg for an 18-20 g
      mouse). The most common symptoms of venom poisoning in mice were sialorrhea,
      respiratory distress, profuse sweating, ataxia, behavior alterations
      (restlessness, somnolence) and hyperglycemia at 3 and 24 hours after subcutaneous
      venom injection (0.5 LD50). The neutralizing capacity of Bioclon (Mexico City)
      and Butantan (Sao Paulo) antivenoms (for a 50% effective dose) was 330 and 292
      microg venom/ml antivenom, respectively. The Biotecnologia (Caracas) antivenom
      did not neutralize the lethal effect of venom. By electrophoresis (SDS-PAGE) was
      demonstrated that the venom contains proteins from less than 14 kd to 97 kd. The
      Western blots indicated immunological reactivity of the three antivenoms with
      most of venom components, including proteins of low molecular mass (<14 kd). The
      results allow to conclude that T. pachyurus venom is neutralized efficiently by
      anti-scorpion antivenoms produced in Mexico and Brasil.

PMID- 15239601
TI  - [Polymorphisms of APO-E in Colombian women with osteoporosis: correlation with
      clinical and social risk variables].
AB  - Several studies have reported an association between apolipoprotein E
      polymorphisms and osteoporosis, specially the genotype APO-E4. In order to
      analyze the APO-E polymorphisms and to identify their association with clinical
      and social variables, a descriptive study was undertaken that included 32 women
      with osteoporosis, from different regions of Colombia. The polymorphisms were
      detected by PCR and RFLP methods. In osteopenia and osteoporosis combined with
      osteopenia were observed the genotype epsilon3/epsilon3 in the 84% (n=27), and
      16% (epsilon3/epsilon4=12.5%, n=4; epsilon4/epsilon4=3.1%, n=1) for the genotypes
      bearing the epsilon4 allele. The same tendency was observed by age of the
      menopause, epsilon3/epsilon3 in the 83% (n=25), and the genotypes bearing the
      epsilon4 allele in the 17% (n=5) (epsilon3/epsilon4=13.3%, n=4;
      epsilon4/epsilon4=3.3%, n=1). No association of APO-E4 was detected with
      socioeconomic stratum, fracture, illness, surgeries, and milk consumption. No
      significant differences were observed in the bone mineral density (BMD) of the
      lumbar column between the genotypes with or without the epsilon4 allele
      epsilon4+/- (epsilon3/epsilon4 0.96+/-0.14 g/cm2); epsilon4+/+ (epsilon4/epsilon4
      0.87+/-0.0 g/cm2); epsilon4-/- (epsilon3/epsilon3 0.86+/-0.16 g/cm2); p=0.49, and
      femoral bone mineral density epsilon4+/- (epsilon3/epsilon4 0.84+/-0.03 g/cm2);
      epsilon4+/+ (epsilon4/epsilon4 0.84+/-0.0 g/cm2); epsilon4-/- (epsilon3/epsilon3
      0.74+/-0.01 g/cm2); p=0.014. However, when exploring the differences of BMD in
      the femoral neck, a significant difference was observed (t=4.17, p=0.05). These
      results confirm epsilon4 allele frequencies similar to those reported for
      caucasian and Japanese, subjects. Larger studies are necessary to elucidate the
      effect of APO-E in bone marrow and the dose-effect relation.

PMID- 15239602
TI  - [Validation of the Diagnostic Interview for Genetic Studies (DIGS) in Colombia].
AB  - An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was
      translated into Spanish for application in studies of psychiatric disorders in
      Colombia. Two Spanish translations of the original English version of DIGS were
      prepared and back-translated into English. A review committee verified the
      linguistic and cultural equivalence of the translations. The evaluator and test
      retest reliability were assessed calculating Cohen's kappa for samples of 65 and
      91 patients respectively. DIGS proved valid in both appearance and content. The
      confidence interval (C.I.) was excellent for schizophrenia (kappa = 0.81, C.I.
      95% = 0.68-0.93), bipolar disorder (kappa = 0.87, C.I. 95% = 0.75-0.99), major
      depressive disorder (kappa = 0.86, C.I. 95% = 0.70-1.00), and for a normal
      diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric
      diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective
      disorder (kappa = 0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was
      excellent for all diagnoses (kappa > 0.8), except for "other psychiatric
      diagnoses" (kappa = 0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the
      DIGS was comprehensible, with face and content validity, and good test-retest and
      evaluator reliability. This translation will be a useful tool for genetic studies
      of psychiatric disorders in Latin America, particularly where schizophrenia and
      affective disorders are involved.

PMID- 15239603
TI  - [Effect of rabies virus infection on the expression of parvalbumin, calbindin and
      calretinin in mouse cerebral cortex].
AB  - Some clinical features of rabies and experimental evidence from cell culture and
      laboratory animals suggest impairment of gabaergic neurotransmission. Several
      types of gabaergic neurons occur in the cerebral cortex. They can be identified
      by three neuronal markers: the calcium binding proteins (CaBPs) parvalbumin (PV),
      calbindin (CB) and calretinin (CR). Rabies virus spreads throughout the cerebral
      cortex; however, rabies cytopathic effects on gabaergic neurons are unknown. The
      expression of calcium-binding proteins (CaBPs) parvalbumin (PV), calbindin (CB)
      and calretinin (CR) was studied in the frontal cortex of mice. The effect of
      gabaergic neurons was evaluated immunohistochemically. The distribution patterns
      of CaBPs in normal mice and in mice infected with 'fixed' or 'street' rabies
      virus were compared. PV was found in multipolar neurons located in all cortical
      layers except layer I, and in pericellular clusters of terminal knobs surrounding
      the soma of pyramidal neurons. CB-immunoreactivity was distributed in two
      cortical bands. One was composed of round neurons enclosed by a heavily labeled
      neuropil; this band corresponds to supragranular layers II and III. The other was
      a weakly stained band of neuropil which contained scattered multipolar CB-ir
      neurons; this corresponds to infragranular layers V and VI. The CR-ir neurons
      were bipolar fusiform cells located in all layers of cortex, but concentrated in
      layers II and III. A feature common to samples infected with both types of
      viruses was a more intense immunoreactivity to PV in contrast to normal samples.
      The infection with 'street' virus did not cause additional changes in the
      expression of CaBPs. However, the infection with 'fixed' virus produced a
      remarkable reduction of CB-immunoreactivity demonstrated by the loss of CB-ir
      neurons and low neuropil stain in the frontal cortex. In addition, the size of CR
      ir neurons in the cingulate cortex was decreased.

PMID- 15239604
TI  - [Gametocyte levels in response to differing malaria treatments in two
      municipalities of Colombia].
AB  - Plasmodium falciparum gametocyte levels are influenced by level of regional
      endemicity, the antimalarial treatment, and the therapeutic response of patients.
      Few previous studies have related these factors in Colombia. Here, gametocytaemia
      was evaluated with respect to two treatment schemes (sulfadoxine/pyrimethamine
      and sulfadoxine/pyrimethamine plus chloroquine), the patient response (adequate
      or failure), and the locality (two areas of varying case frequency). One hundred
      forty-eight residents of Turbo and Zaragoza (Antioquia), all with uncomplicated
      malaria, were evaluated. The gametocytaemia and the rates of clinical malaria at
      the beginning of treatment were greater in Turbo than in Zaragoza. No
      statistically significant differences in the gametocytaemia by treatment schemes
      or therapeutic responses were noted, although the patients who received SP had
      more gametocytes than those treated with SP+CQ. Gametocytaemia was not correlated
      with asexual parasitemia or sex and age of patient. The difference in the level
      of gametocytaemia between Turbo and Zaragoza appears to be influenced by the time
      elapsed between the appearance of symptoms and the beginning of treatment.

PMID- 15239605
TI  - [Presence of Salmonella as a risk to public health in the Caribbean zone of
      Colombia].
AB  - Salmonella is frequently involved in diarrhoeal disease throughout the world and
      is disseminated mainly by food, polluted waters or infected food-handlers. In
      Colombia, the serotypes of Salmonella and their distribution in food have not
      been characterized. Therefore, the objective was to establish the epidemiology of
      Salmonella in the Caribbean zone. Six hundred thirty-six samples were obtained in
      fast food outlets located in city squares or markets of Barranquilla (n=245),
      Monteria (n=222), Sincelejo (n=87) and Cartagena (n=82). Salmonella was isolated
      by the conventional methods recommended by the United States Food and Drug
      Administration. Briefly, 25 g of each sample was inoculated in 225 ml of broth.
      Twenty-four hours later, a 1 ml aliquot was inoculated onto selective media for
      Salmonella. Suspicious colonies were identified by conventional biochemical tests
      and confirmed by conventional serology for Salmonella detection. Forty-seven
      Salmonella serotypes were isolated from meat (40%), sausage (25%), cheese (13%),
      pig (13%), chicken (4.2%) and egg 'arepas' (4.2%). The serologic characterization
      indicated the following serotypes: S. Anatum (26%), S. Newport (13%), S.
      Typhimurium (9%), S. Gaminara (9%) and S. Uganda (9%). No statistically
      significant Salmonella isolations among 4 socioeconomic categories were observed
      (p=0.05). However, differences were observed when rates were compared for
      Salmonella by food type for socioeconomic categories 1, 2 and 3 (p<0.05),
      categories 2 and 3 did not show differences between them (p>0.05).

PMID- 15239606
TI  - Differentiation of an adult neuron cell line increases susceptibility to rabies
      infection.
AB  - A wide variety of in vitro models have been used for studying rabies infection,
      however, currently, no central nervous system (CNS) adult neuron cultures are
      available. The current study determined the susceptibility to rabies infection in
      an adult CNS neuron cell line (CAD-R1). Cultures of CAD-R1 cells were held for 5
      days in medium containing serum (undifferentiated CAD-R1 cells) or in serum-free
      medium (differentiated CAD-R1 cells). They were then infected with highly
      neurotropic rabies virus (RV) strain (CVS), obtained from fibroblastic cells (CVS
      BHK) or from adult mouse brain (CVS-MB). Undifferentiated and differentiated
      cells were infected with the two RV strains, but the percentage of infected cells
      in differentiated cultures was significantly greater (83% and 79%, respectively)
      than in undifferentiated cells (51% and 60%) (Student's t test<0.05).
      Susceptibility to infection apparently depended on cellular differentiation
      state, possibly due to acquisition of additional morphological and biochemical
      characteristics during the differentiation process that made them more
      susceptible to RV infection. Therefore, CAD R1 cells may represent a good model
      for RV infection, making them a useful tool for studying RV neurotropism,
      infection pathogeny, isolation of street virus or producing safer and most potent
      vaccines.

PMID- 15239608
TI  - Hepatocyte transplantation.
AB  - Isolated hepatocyte transplantation has long been recognized as a potential
      treatment for life-threatening liver disease. The basis for proceeding with
      clinical trials has been established by the extensive laboratory work in animal
      models. Human hepatocyte transplantation has been applied in individual cases and
      very small, uncontrolled series. Data, although sparse, demonstrate the safety
      and feasibility of this approach and are supportive, if less than conclusive, of
      effectiveness. The experience of hepatocyte transplantation in the laboratory and
      clinical arenas is reviewed and discussion will examine what is believed to be
      the primary cause for the slow growth of this technology in the clinical setting,
      namely a severe shortage of usable primary human hepatocytes. The potential of
      isolated hepatocyte transplantation remains largely untapped and awaits alternate
      sources of cells for transplantation other than those from discarded human
      cadaveric livers.

PMID- 15239607
TI  - [Comparison of the indirect immunofluorescent (IFAT), ELISA test and the
      comercial Chagatek test for anti-Trypanosoma cruzi antibodies detection].
AB  - Chagas disease is a public health problem in Colombia, particularly in the
      eastern region. Because of human migration from rural areas to urban centers, the
      possibility of transfusional transmission becomes increasingly important. However
      the risk can be minimized by a careful screening of blood donors by means of
      serological tests. Colombian blood banks use comercial, foreign serological tests
      for screening for T. cruzi infection. The purpose of the current study was to
      compare the IFAT and ELISA tests (both use antigen obtained from Colombian
      strains) with the comercially available Chagatek tests. Sera of blood donors were
      classified in two groups on the basis of the IFAT: group I, 15 positive patients
      and group II, 14 negative patients. Sera from each group were tested by the ELISA
      and Chagatek tests. The ELISA test detected 100% of the patients as positive in
      group I and 7% (1/14) of patients as positive in group II. The Chagatek test
      detected 93% (14/15) of the patients as positive in group I and 50% (7/14) in
      group II. The kappa index for concordance between the ELISA and IFAT tests was
      0.93 (95% C.I.: 0.80-1.00); between IFAT and Chagatek 0.43 (95% C.I.: 0.26-0.62),
      and between ELISA and Chagatek 0.49 (95% C.I.: 0.31-0.67). These results
      highlighted the importance of using autochtonous Colombian strains as antigens in
      screening tests for blood donors.

PMID- 15239609
TI  - Effects of anti-inflammatory cytokine agent (FR167653) and serine protease
      inhibitor on warm ischemia-reperfusion injury of the liver graft.
AB  - BACKGROUND: The shortage of donors has become a serious problem. Some institutes
      have tried to use grafts retrieved from non-heart-beating donors (NHBDs), but the
      results have not been satisfactory. This study clarifies the effects of
      nafamostat mesilate (NM), a strong serine protease inhibitor, and FR167653, a
      suppressant of both tumor necrosis factor-alpha and interleukin-1beta release, on
      warm ischemia-reperfusion injury and establishes the procurement of the grafts
      for a successful liver transplant using uncontrolled NHBDs. METHODS: Male Wistar
      rats were divided into five groups as follows (n = 5): (1) heart-beating (HB)
      group, in which livers were retrieved from heart-beating donors; (2) non-heart
      beating (NHB) group, in which livers were retrieved from NHBDs; (3) NM group, in
      which livers were retrieved from NHBDs pretreated with NM (0.2 mg/kg/hr, for 30
      min); (4) FR group, in which livers were retrieved from NHBDs pretreated with
      FR167653 (2 mg/kg); and (5) FR+NM group, in which livers were retrieved from
      NHBDs pretreated with FR167653 and NM. The livers were perfused for 60 min with
      Krebs-Henseleit bicarbonate buffer after cold preservation 6 hr. RESULTS: In the
      NHB group, the values of interleukin-1beta, tumor necrosis factor-alpha,
      thromboxane B2, and leukotriene B4, and the expressions of nuclear factor-kappaB,
      activating protein 1, and cyclooxygenase-2 were significantly higher than those
      in the HB group. In the FR+NM group, those values were low, the structure of the
      sinusoids was preserved, and the sinusoidal lumen was maintained (the same as
      observed in the HB group). CONCLUSIONS: FR167653 and NM inhibited the induction
      of inflammatory cytokines and arachidonic acid cascade mediators. This combined
      therapy was effective in preserving sinusoidal microcirculation in the liver
      grafts from NHBDs.

PMID- 15239610
TI  - Effects of AGI-1096, a novel antioxidant compound with anti-inflammatory and
      antiproliferative properties, on rodent allograft arteriosclerosis.
AB  - BACKGROUND: AGI-1096 is a novel phenolic intracellular antioxidant with anti
      inflammatory and antiproliferative properties. In vitro, AGI-1096 inhibited the
      inducible expression of vascular cell adhesion molecule (VCAM)-1, E-selectin, and
      monocyte chemoattractant protein (MCP)-1 in endothelial cells and tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta secretion from lipopolysaccharide
      (LPS)-stimulated peripheral blood mononuclear cells. It also inhibited serum
      stimulated proliferation of aortic smooth-muscle cells. In vivo, AGI-1096
      demonstrated anti-inflammatory properties in a murine delayed-type
      hypersensitivity model. Given these antioxidant, anti-inflammatory and
      antiproliferative properties, we reasoned that AGI-1096 may be able to prevent
      chronic allograft arteriosclerosis. This hypothesis was tested in a rodent aortic
      transplantation model. METHODS: Donor descending aortas from August-Copenhagen
      Irish rats were heterotopically transplanted into Lewis rat abdomens in end-to
      end fashion. Animals were assigned to six groups as follows: AGI-1096 0 mg/kg per
      day (vehicle, n = 10), 10 mg/kg per day (n = 10), 20 mg/kg per day (n = 10), 40
      mg/kg per day (n = 10), positive control (cyclosporine A 10 mg/kg per day by oral
      gavage, n = 10), and isograft negative control (Lewis-to-Lewis, n = 5). AGI-1096
      was administrated subcutaneously to recipient animals three days before the
      surgery and for 90 days thereafter. On day 90, the paraffin-embedded allograft
      sections were stained with Elastin-van Gieson's stain, and the intima/media (I/M)
      ratio and luminal narrowing (1%LN) was assessed by digital morphometry. RESULTS:
      AGI-1096 demonstrated dose-dependent lowering of the I/M ratio and %LN when
      compared with vehicle controls. CONCLUSION: This is the first study to show that
      treatment of allograft recipients with AGI-1096 decreases the incidence of
      transplant arteriosclerosis. These data suggest that AGI-1096 may be a promising
      new therapeutic agent for use in clinical transplantation.

PMID- 15239611
TI  - Portal donor-specific blood transfusion and mycophenolate mofetil allow steroid
      avoidance and tacrolimus dose reduction with sustained levels of chimerism in a
      pig model of intestinal transplantation.
AB  - BACKGROUND: In a pig model of intestinal transplantation, we previously showed
      that hepatic conditioning through portal donor-specific blood transfusion
      (pDSBT), high-dose tacrolimus (TAC), and steroids prevented rejection and
      increased survival Our current study tests a protocol of pDSBT, short-term
      mycophenolate mofetil (MMF), and low-dose TAC to eliminate the use of steroids,
      reduce TAC dosage, and increase the level of chimerism in the peripheral blood.
      MATERIALS AND METHODS: Four groups of outbred, mixed lymphocyte culture (MLC)
      reactive pigs underwent bowel transplants and pDSBT. Immunosuppression (group 1,
      high-dose TAC and steroids; group 2, low-dose TAC and MMF; group 3, low-dose TAC,
      MMF, and aminoguanidine; group 4, low-dose TAC, MMF, and arginine) was
      discontinued after 28 days. RNA was extracted from intestinal graft and native
      liver biopsies for cytokine measurements. Chimerism levels were determined using
      a Q-PCR analysis. RESULTS: Pig survival and death rates due to rejection did not
      significantly differ between the four groups. Chimerism levels determined by Q
      PCR analysis were not different until day 28. After discontinuation of
      immunosuppression, we noted a trend (P = 0.15) toward higher mean chimerism
      levels on day 60 for groups 2, 3, and 4 (9%) vs. group 1 (0.5%). Tissue cytokine
      and serum nitrate levels did not significantly differ between the four groups.
      Attempts to modify nitric oxide synthase activity offered no added benefit.
      CONCLUSIONS: The combination of pDSBT, MMF, and low-dose TAC (vs. high-dose TAC
      and steroids) allowed sustained levels of mixed chimerism to develop after
      discontinuation of immunosuppression.

PMID- 15239612
TI  - Metabolic interaction between cyclosporine and sirolimus.
AB  - BACKGROUND: When the immunosuppressants cyclosporine (CsA) and sirolimus (SRL)
      are co-administered to transplant patients, lower doses are used than when either
      drug is given alone. Since both drugs share similar transport and metabolic
      pathways, there is the potential for an interaction leading to unpredictable
      effects. Furthermore, both drugs affect the activity of cytochrome P450 3A1/2
      (CYP3A1/2), the rat parallel to human CYP3A4, and the multidrug transporter P
      glycoprotein (Pgp). METHODS: To clarify the role of metabolic enzymes and
      membrane transporters involved in the disposition of both drugs, we examined
      hepatic CYP3A1/2, Pgp, and multidrug resistance gene (mdr) mRNA during chronic
      therapy with CsA and SRL in salt-depleted rats. Specifically, rats were given
      intravenous doses of CsA 2.5 mg/kg and SRL 1 mg/kg, alone or in combination, for
      two weeks via constant rate intravenous infusion. RESULTS: CsA treatment
      inhibited hepatic CYP3A1/2 protein expression, catalytic activity, and mRNA
      levels. SRL dosing suppressed CYP3A1/2 protein expression and catalytic activity,
      without affecting mRNA. With combined dosing, however, there was a much greater
      reduction. Hepatic Pgp protein levels were elevated after treatment with either
      drug alone, as well as with combined dosing. Compared to controls, there were
      significant increases in mdr1a and mdr1b mRNA levels in all treatment groups,
      with the combined drugs causing the greatest increase. CONCLUSIONS: Both CYP3A1/2
      and Pgp participate in the disposition of CsA and SRL in rats. Changes in the
      individual activities of CYP3A1/2 and Pgp may contribute to an interaction
      between CsA and SRL resulting in unanticipated effects during chronic therapy.

PMID- 15239613
TI  - Hepatic allograft arterialization by means of the gastroduodenal bifurcation
      (branch patch) as a prognostic factor.
AB  - INTRODUCTION: Because of the current shortage of cadaveric organs, it is
      important to determine preoperatively those variables that are readily available,
      inexpensive, and noninvasive that can predict a higher incidence of hepatic
      artery thrombosis (HAT). MATERIAL AND METHODS: From April 1986 to October 2001,
      717 patients underwent 804 liver transplants. All the arterial reconstructions
      were performed with fine (7-0) monofilament sutures in an interrupted fashion.
      Two methods were used: group I, end-to-end arterial anastomosis, and group II,
      the gastroduodenal branch patch. RESULTS: After a mean follow-up of 72 (range 3
      174) months, HAT was observed in 19 patients (overall incidence 2.4%). End-to-end
      anastomosis (group I) was performed in 39.50% (316) of cases, and HAT developed
      in 14 (4.4%) cases. Branch-patch anastomoses (group II) were carried out in 60.5%
      (488) of the patients; the presence of HAT was detected in five cases (1.03%) (P
      = 0.03, P < 0.05). A total of 21 variables were selected in the univariate
      analysis; however, after the multivariate analysis, all but two of the factors
      lost statistical significance, and these corresponded to the type of arterial
      reconstruction (gastroduodenal branch patch vs. end-to-end) and the ABO
      compatibility. CONCLUSIONS: Liver transplantation with compatible grafts using
      branch-patch anastomosis for the arterialization (both manipulative by the
      transplant team) reduces HAT-derived loss of grafts, with the consequent increase
      in graft availability and reduced mortality rate on the waiting list.

PMID- 15239614
TI  - Serologic evidence of Chlamydia pneumoniae infection as a long-term predictor of
      cardiovascular death in renal transplant recipients.
AB  - BACKGROUND: Cardiovascular disease is the main cause of death with a functioning
      graft in renal transplant recipients. Elevated levels of C-reactive protein (CRP)
      and evidence of chronic Chlamydia pneumoniae infection have been linked to
      cardiovascular disease and survival in patients with normal renal function and
      patients with end-stage renal disease on dialysis. So far, no such data have been
      available in renal transplant recipients. METHODS: CRP, immunoglobulin (Ig)G and
      IgA antibodies to C. pneumoniae, and classic risk factors were compiled in 143
      patients who underwent renal transplantation between January 1989 and April 1991.
      Samples were collected at transplantation, 1 year later, and at study end.
      Cardiovascular disease, death, and graft loss were documented during follow-up.
      RESULTS: A total of 44 patients died during a mean follow-up of 10 years. Cardiac
      events were responsible for 37% of deaths. Age, gender, number of
      antihypertensive drugs, and seropositivity for IgG and IgA antibodies to C.
      pneumoniae, but not CRP levels, were significantly associated with cardiac death.
      C. pneumoniae serology and CRP levels, however, did not influence graft survival.
      Age, presence of diabetes, calcium phosphorus ion product, number of
      antihypertensive drugs, serum creatinine at 1 year, and presence of chronic
      rejection were all negatively correlated with graft survival. CONCLUSIONS:
      Serologic evidence of chronic C. pneumoniae infection is associated with
      mortality as the result of cardiovascular disease in renal transplant recipients.
      CRP serum levels do not predict cardiac death in renal transplant recipients, in
      contrast with patients with normal renal function and patients on dialysis.

PMID- 15239615
TI  - Detection of Chlamydia pneumoniae in liver transplant patients with chronic
      allograft rejection.
AB  - BACKGROUND: Chlamydia pneumoniae is one of the possible pathogenetic factors of
      atherosclerotic processes. Foam cell arteriopathy is a generally accepted
      pathologic feature of chronic liver allograft rejection and has several
      similarities to the early lesions of atherosclerosis. The aim of the authors'
      study was to show any existing correlation between the occurrence of Chlamydia
      pneumoniae and the presence of foam cell arteriopathy in transplanted livers with
      chronic rejection. METHODS: Ten liver samples from patients with chronic liver
      rejection including foam cell arteriopathy and 10 liver samples from healthy
      individuals were analyzed for the presence of Chlamydia pneumoniae by specific
      immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two
      transplant patients with chronic liver rejection without any evidence of foam
      cell arteriopathy and nine patients with acute liver allograft rejection were
      also investigated by PCR. RESULTS: In all 10 rejected liver samples, Chlamydia
      pneumoniae was detected by PCR, whereas only one of the healthy control samples
      and one of the samples with acute rejection were found to be positive.
      Immunohistochemistry showed similar results. The positive signals of Chlamydia
      pneumoniae were localized mainly in the hepatocytes, sinusoidal and
      perisinusoidal cells, and the cells of portal tracts, whereas most of the altered
      hepatic arteries showed no or very weak positivity. CONCLUSIONS: The results
      strongly suggest an association between the occurrence of Chlamydia pneumoniae
      and the presence of foam cell arteriopathy in transplanted livers.

PMID- 15239616
TI  - Attrition of potential bone marrow donors at two key decision points leading to
      donation.
AB  - BACKGROUND: The National Marrow Donor Program (NMDP) has had remarkable success
      at recruiting potential bone marrow donors and recently has become increasingly
      focused on the retention of registered volunteers. This study extends the
      authors' work examining factors associated with attrition from the registry. Its
      goal was to determine which characteristics from six psychosocial domains were
      associated with attrition at two key stages leading to donation. METHODS:
      Questionnaires were mailed to potential donors after they were contacted as a
      potential match and had decided whether or not to continue toward donation. Our
      final sample included 1,727 volunteers who decided to continue with typing at the
      DR stage and 195 volunteers who decided to continue at the confirmatory typing
      (CT) stage as well as 179 and 169 individuals, respectively, who declined further
      participation in the registry at DR and CT stages. RESULTS: Bivariate analyses
      indicated that multiple factors in all six domains (demographics, volunteer
      related, general psychosocial, recruitment-related, donation-related, and contact
      with center staff) were associated with discontinued registry participation.
      Logistic regression indicated that unique associations were concentrated in
      volunteer-related, donation-related, and contact with center domains.
      CONCLUSIONS: Findings suggested that intrinsic commitment to donation, more
      realistic expectations, fewer medical concerns, and greater contact with the
      donor center were all associated with lower attrition. Possible interventions to
      reduce attrition are discussed.

PMID- 15239617
TI  - Multispiral computed tomographic angiography of renal arteries of live potential
      renal donors: a review of 118 cases.
AB  - OBJECTIVES: Review of the angiographic data of 118 live kidney donors was
      performed to assess the renal vessel anatomy; compare the findings with the
      perioperative findings using multislice spiral (MS) computed tomographic
      angiography (CTA) with the use of 50 mL of intravenous contrast; determine the
      sensitivity of this technique in the workup of live potential renal donors; and
      finally to discuss and compare the results of the present study with the reported
      results using single-slice spiral (SS) CTA, magnetic resonance angiography (MRA),
      and conventional angiography (CA). METHODS: Retrospective analysis of the
      angiographic data of 118 of prospective live kidney donors was performed. All
      donors underwent renal angiography on MSCTA scanning using 50 mL of intravenous
      contrast with 1.25-mm slice thickness followed by maximum intensity projection
      and virtual rendering techniques postprocessing algorithms. Analysis was made on
      imaging and intraoperatively for the number of renal arteries as well as their
      bifurcation pattern, location, vessel caliber, length, and venous anatomy, and
      these were then compared with each other. RESULTS: MSCTA showed clear delineation
      of the main renal arteries in all the donors with detailed vessel morphology. The
      study also revealed a 100% sensitivity in the detection of accessory renal
      vessels, which had an overall incidence of 26.67%, with the most common
      distribution in the perihilar region. CONCLUSIONS: The present study showed a
      100% sensitivity and specificity in the visualization and detection of main and
      accessory renal vessels with the use of only 50 mL of intravenous contrast with
      similar results seen with CA which has so far been considered the "gold
      standard." The results on MSCTA were also better than those with the use of SSCTA
      and MRA in the workup of liver renal donors, with the above technique also
      proving to be more cost effective. The overall incidence of supernumerary vessels
      was the same as reported in the literature; however, a higher incidence of single
      aberrant vessels was seen on the right side, contrary to what has been suggested
      so far and was attributable to improved detection of accessory vessels less then
      2 mm in diameter.

PMID- 15239618
TI  - A comparative prospective study of two available solutions for kidney and liver
      preservation.
AB  - BACKGROUND: Viaspan (University of Wisconsin [UW]) solution is the gold standard
      for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low
      potassium, low-viscosity solution, initially used for heart and lung
      preservation. We have performed a prospective multicenter study to compare the
      role of these cold-storage solutions on kidney and liver recovery after
      transplantation. PATIENTS AND METHODS: From March 15, 2000 to December 31, 2001,
      441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver
      transplants (LT) were included in the study. RESULTS: Perfusate volume used was
      significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL
      in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were
      significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and
      92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L,
      respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups
      were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival
      being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT,
      delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively;
      PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient
      survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS).
      CONCLUSIONS: CEL solution was shown to be as effective as UW in both liver and
      kidney preservation. In LT patients, biliary function recovery is significantly
      better in the CEL group. CEL solution represents an efficacious option in
      multiorgan harvesting.

PMID- 15239619
TI  - Resource use and treatment costs after kidney transplantation: impact of
      demographic factors, comorbidities, and complications.
AB  - BACKGROUND: Our goal was to quantify outcomes, resource use, and treatment costs
      for the first 2 years after renal transplantation in a "real-life" European
      setting and to assess the impact of preoperative risk factors and postoperative
      complications on treatment costs. METHODS: Inpatient and outpatient records of
      all patients who received a renal transplant at Medizinische Hochschule Hannover,
      Germany, between January 1998 and July 2000, were evaluated. Key clinical events
      were recorded. Direct costs were calculated for primary hospitalization, the
      remainder of year 1, and year 2 after transplantation. Cost of organ procurement,
      pretransplant care, and transplant surgery were excluded. Cost consequences for
      key clinical events were determined. RESULTS: Of 204 patients undergoing
      transplantation, 195 and 149 completed 1 year and 2 years of follow-up,
      respectively. The outcomes of years 1 and 2, respectively, were as follows: graft
      failure, 5.4%, 0.7%; acute rejection, 35.9%, 5.4%; cytomegalovirus (CMV)
      infection, 29.2%, 2.0%; and delayed graft function, 30.9%. Costs for primary
      hospitalization, the remainder of year 1, and year 2 averaged Euro 15,380, Euro
      18,636, and Euro 14,484, respectively. Cost-driving events included graft failure
      Euro 36,228), acute rejection (Euro 9,638), delayed graft function (Euro7,359),
      and CMV infection (Euro 4,149). Graft failure and acute rejection for year 1 also
      added significantly to the costs for year 2. CONCLUSIONS: These results show that
      posttransplant clinical outcomes result in a significant increase in treatment
      costs. Because the economic impact of primary causes of chronic rejection (acute
      rejection and CMV) and delayed graft function is substantial, careful selection
      of the most appropriate immunosuppressive regimen is essential.

PMID- 15239620
TI  - Infection with human herpesvirus 8 and transplant-associated gammopathy.
AB  - BACKGROUND: The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple
      myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is
      transmitted by organ transplantation, representing a unique model with which to
      investigate primary HHV-8 infection. METHODS: The authors studied the incidence
      of clonal gammopathy in renal transplant recipients and correlated it with
      previous and recent HHV-8 infection. RESULTS: Clonal gammopathy was observed in
      31 of 162 (19%) HHV-8-seronegative patients, in 5 of 17 (29%) HHV-8-seropositive
      patients, and in 9 of 24 (38%) HHV-8 seroconverters within 5 years after
      transplantation. Gammopathy was often transient, and no progression to myeloma
      was observed. Two patients with persistent gammopathy developed B-cell lymphoma.
      In a logistic regression model, HHV-8 serostatus of the graft recipient was
      significantly associated with subsequent development of gammopathy, with a
      relative risk (RR) of 1.9 and a 95% confidence interval (CI) of 0.5 to 6.4 for an
      HHV-8-seropositive recipient and an RR of 2.9 and a 95% CI of 1.01 to 8.0 for
      seroconverters as compared with baseline (HHV-8 seronegative). Other significant
      variables were cytomegalovirus (CMV) serostatus and the intensity of
      immunosuppression (RR of 10.4 and 95% CI of 2.6-41.7 for a CMV-negative recipient
      with a CMV-positive donor vs. a CMV-negative recipient with a CMV-negative donor
      and RR of 17.6 and 95% CI of 2.0-150.8 if OKT3 was used vs. no use of
      antilymphocytic substances). CONCLUSIONS: Transplant recipients with HHV-8
      infection are more likely to develop clonal gammopathy. However, this risk is
      much lower than the risk conferred by CMV infection and antilymphocytic therapy,
      arguing against a major role of HHV-8 infection in the pathogenesis of clonal
      plasma cell proliferation.

PMID- 15239622
TI  - Glucose metabolism after pancreas transplantation: cyclosporine versus
      tacrolimus.
AB  - BACKGROUND: The results of the new immunosuppressants in simultaneous pancreas
      kidney transplantation (SPK) concerning organ survival and rejection rates are
      excellent. Tacrolimus as well as cyclosporine are assumed to be diabetogenic;
      however, there are no comparative studies investigating their effects on glucose
      metabolism. METHODS: One hundred thirty-six type 1 diabetic patients who had
      undergone successful SPK were investigated. Glucose and insulin levels during an
      oral glucose tolerance test as well as hemoglobin (Hb) A1c were analyzed.
      Investigations were performed early (3 months, n = 136) and late (3 years, n =
      83) after transplantation. Graft recipients were grouped according to the first
      line immunosuppression: group 1, cyclosporine; group 2, tacrolimus. There were no
      differences concerning age, gender, body mass index, and renal function between
      the groups. RESULTS: Early after transplantation, there was no difference between
      the groups concerning fasting glucose, HbA1c levels, basal and stimulated insulin
      secretion, and incidence of normal glucose tolerance. Late after transplantation,
      the incidence of a normal glucose tolerance tended to be lower (70% vs. 78%),
      whereas HbA1c (5.3% vs. 5.0%) and fasting glucose (81 vs. 78 mg/dL) levels tended
      to be higher in tacrolimus-treated patients. However, these differences were not
      significant. Insulin secretion was not reduced in the tacrolimus group.
      CONCLUSIONS: Concerning glucose metabolism and secretory capacity of the pancreas
      graft, no significant differences were found comparing tacrolimus- versus
      cyclosporine-treated graft recipients.

PMID- 15239624
TI  - A simple and accurate formula to estimate left hepatic graft volume in living
      donor adult liver transplantation.
AB  - BACKGROUND: In the field of living-donor adult liver transplantation, a small-for
      size graft often occurs, particularly when using left-lobe grafts. This is
      because of the limited volumes associated with left-lobe grafts. The accurate
      preoperative evaluation of graft volumes is crucial to avoid this complication.
      The aim of this study is to clarify the usefulness of a new formula to estimate
      the left-lobe graft volume. METHOD: In 61 left-lobe grafts, a new formula was
      created with stepwise regression analysis using the following variables: height,
      weight, the thoracic and abdominal distance from anterior to posterior side (A
      P), and distance from left to right side (L-R) of the initial 20 donors. With
      another 41 donors, the difference between the actual and estimated graft volume
      using the formula and two- and three-dimensional computed tomography was
      prospectively evaluated. RESULTS: On the basis of the results of the stepwise
      regression analysis, a new formula was created as follows: graft volume (ml) =
      313.4 + 7.7 x weight (kg)-12.6 x thoracic L-R (cm). The difference between the
      actual and estimated graft volumes using the formula was significantly better
      (10.8 +/- 9.5%) than that of the volumetry using two-dimensional computed
      tomography (16.3 +/- 10.1%) (P < 0.05). CONCLUSIONS: In conclusion, the new
      formula can estimate the actual graft volume more accurately than conventional
      volumetry with two-dimensional computed tomography. The formula is useful to
      estimate the volume of left-lobe graft in living-donor adult liver
      transplantation.

PMID- 15239623
TI  - Early rapid loss followed by long-term consolidation characterizes the
      development of lumbar bone mineral density after kidney transplantation.
AB  - BACKGROUND: Bone mineral density (BMD) decreases significantly early after renal
      transplantation. This prospective study was designed to evaluate the long-term
      lumbar BMD development. METHODS: Sixty-three renal-transplant recipients (mean
      age 44 +/- 12 years, 37 [59%] male) underwent serial yearly posttransplant
      laboratory parameter and BMD measurements of the lumbar spine (dual energy x-ray
      absorptiometry). Combined maintenance immunosuppression included prednisolone in
      95% of patients. The minimum number of consecutive scans was three; the maximum
      number seven (n = 15). Examinations were performed between 3 +/- 2 and 68 +/- 4
      months posttransplant. RESULTS: BMD was significantly lower compared with healthy
      controls at all times after transplantation. t scores were below -1. BMD
      development revealed a biphasic pattern: between 3 +/- 2 and 10 +/- 2 months, a
      significant BMD decrease of -0.016 +/- 0.055 g/cm2 (-1.6%, P = 0.024) occurred.
      Later, a moderate increase resulting in BMD stability until the sixth year
      posttransplant was detected. Within the first year, posttransplant osteocalcin
      (from 19 +/- 15 to 32 +/- 23 microg/L) and calcitriol (from 24 +/- 15 to 43 +/-
      24 ng/L) displayed a significant increase. Compared with patients with a
      pronounced decrease, patients with a substantial increase in early posttransplant
      BMD had a lower baseline BMD (0.989 +/- 0.131 vs. 1.149 +/- 0.202 g/cm2 [P =
      0.0122]) and lower creatinine levels (105 +/- 23 vs. 141 +/- 53 mmol/L [P =
      0.0227]). CONCLUSION: Our study confirms a significant decrease of lumbar BMD
      early after renal transplantation. Bone loss was less pronounced than previously
      described. The longitudinal follow-up verifies a previously assumed biphasic
      lumbar BMD development: after the first year, no further significant bone loss
      occurred, and bone density remained relatively stable at significantly lower
      levels compared with healthy controls.

PMID- 15239621
TI  - Wound-healing complications after kidney transplantation: a prospective,
      randomized comparison of sirolimus and tacrolimus.
AB  - BACKGROUND: Sirolimus has been associated with an increased risk of wound-healing
      complications in several retrospective analyses. The authors compared the rates
      of wound-healing complications in renal allograft recipients in a prospective,
      randomized trial of sirolimus-mycophenolate mofetil-prednisone versus tacrolimus
      mycophenolate mofetil-prednisone. METHODS: All patients received antithymocyte
      globulin induction. In the first phase of the study, patients (n = 77) were
      included regardless of body mass index (BMI). In the second phase (n = 46
      patients), the authors excluded patients with a BMI greater than 32 kg/m2, and
      the target trough sirolimus level was lowered to 10 to 15 ng/mL (previously 15-20
      ng/mL). Multivariate logistic regression analyses were performed to identify
      predictors of wound complications. RESULTS: Fifty-nine patients received
      tacrolimus and 64 received sirolimus and were included in subsequent analyses.
      The incidence of complications was 8% (5 of 59) in the tacrolimus group and 47%
      (30 of 64) in the sirolimus group (P < 0.0001). Rates of perigraft fluid
      collections, superficial wound infections, and incisional herniae were
      significantly higher in the sirolimus group. Multivariate logistic regression
      showed only sirolimus (P = 0.0001) and BMI (P = 0.0021) to independently
      correlate with complications. In the first phase of the study, the wound
      complication rate in the sirolimus group was 55% (21 of 38 patients). After
      excluding obese recipients and decreasing the target sirolimus level, the wound
      complication rate in the sirolimus group was 35% (9 of 26 patients; P = 0.1040).
      CONCLUSIONS: The use of sirolimus-based immunosuppressive regimens leads to a
      higher incidence of wound-healing complications and will require new approaches
      to patient selection and management to decrease their incidence.

PMID- 15239625
TI  - Reduced incidence of hyperuricemia, gout, and renal failure following liver
      transplantation in comparison to heart transplantation: a long-term follow-up
      study.
AB  - BACKGROUND: Hyperuricemia and gout are common complications of heart
      transplantation, reaching a prevalence of 84% and 30%, respectively, in heart
      transplant recipients. In contrast, they are seldom reported following orthotopic
      liver transplantation (OLT). METHODS: We retrospectively evaluated 75 consecutive
      liver transplant recipients and 47 consecutive heart transplant recipients,
      followed for at least 3 years after transplantation in a single transplantation
      center in Jerusalem, Israel. Data was collected on demographic and clinical
      variables, levels of uric acid, the occurrence of gout, renal function, and
      variables effecting hyperuricemia, such as weight and medications. RESULTS:
      Clinical gout was significantly more prevalent in heart recipients than in liver
      recipients (25.5% and 2.6%, respectively). Hyperuricemia was present in 100% of
      heart recipients, with an average uric acid level of 451 micromol/l, as compared
      with 85.7% and 403 micromol/l for liver recipients (P < 0.001 for both
      variables). Univariate analysis identified several parameters which significantly
      influenced the difference in hyperuricemia and gout among the two groups
      including age, gender, rejection episodes, hypertension, diabetes mellitus, the
      level of uric acid prior to transplantation, and the use of cyclosporine A,
      diuretics, steroids, and aspirin. Use of tacrolimus and azathioprine were
      associated with decreased incidence of hyperuricemia and gout. Multivariate
      analysis identified the type of transplantation as the only independent risk
      factor predicting the development of hyperuricemia and gout. CONCLUSION: Clinical
      gout and hyperuricemia were significantly more prevalent in heart recipients than
      in liver recipients. The disparity can be explained by differences in age, gender
      and renal function among the groups, as well as by the use of different
      medication regimens.

PMID- 15239626
TI  - Human immune responses to porcine endogenous retrovirus-derived peptides
      presented naturally in the context of porcine and human major histocompatibility
      complex class I molecules: implications in xenotransplantation of porcine organs.
AB  - BACKGROUND: Porcine endogenous retroviruses (PERV) have been shown to infect
      human cells, raising concerns regarding safety of xenotransplantation. In
      patients exposed to porcine tissues, no PERV infection has been observed. This
      study was designed to develop human CD8+ cytotoxic T lymphocytes (CTL) against
      PERV-derived peptides presented in the context of human leukocyte antigen (HLA)
      or swine leukocyte antigen (SLA) class I molecules and to define dominant
      epitopes contributed by PERV. METHODS: Human CD8+ CTL were generated against
      porcine aortic endothelial cells (PAEC). Peptides presented on SLA class I
      molecules were acid eluted and fractionated by reverse-phase high-performance
      liquid chromatography. Peptide fractions that restored lysis of acid-stripped
      PAEC were sequenced by tandem mass spectrometry. Human CD8+ CTL were generated
      against PERV envelope-derived peptides and PERV-infected human cells to identify
      immunodominant PERV-derived epitopes. RESULTS: We identified two peptides derived
      from retroviral transactivating regulatory protein (AHQDPLPEQP) and retroviral
      transcription factor (PQKPFVT) recognized by human CD8+ CTL in the context of SLA
      class I. Computer-assisted analysis identified nine PERV-envelope-derived 9-mer
      peptides with high affinity for the HLA-A2 molecule (Env-1-9). PERV-specific CD8+
      CTL generated in vitro identified the immunodominant Env-5 peptide (303-311,
      KLFSLIQGA) and demonstrated HLA-A2-restricted cytotoxicity against PERV-infected
      human cells. CONCLUSIONS: Our results indicate that PERV-derived peptides are
      presented naturally on porcine and human major histocompatibility complex class I
      molecules. CD8+ CTL responses elicited against dominant SLA and HLA class I
      restricted PERV-derived epitopes may play an important role in xenograft
      rejection and in containment of PERV infection of human cells after
      xenotransplantation.

PMID- 15239627
TI  - Serial peripheral blood interleukin-18 and perforin gene expression measurements
      for prediction of acute kidney graft rejection.
AB  - BACKGROUND: We and others have shown that expression of the cytotoxic T
      lymphocyte effector gene perforin in the peripheral blood is a strong predictor
      of acute rejection in the early posttransplant period. In the present study we
      investigated whether interleukin (IL)-18, an immunostimulatory gene that up
      regulates perforin-dependent cytotoxicity and promotes tissue damage through
      other noncytotoxic T-lymphocyte mechanisms alone or in combination with perforin
      gene expression, may serve as a better predictor of renal allograft rejection in
      the first weeks after transplantation. METHODS: Peripheral blood was collected
      twice weekly, and gene expression was measured using real-time polymerase chain
      reaction. RESULTS: Recipients with acute rejection (n = 17) showed higher levels
      of perforin and IL-18 transcript on days 5 to 7, 8 to 10, and 11 to 13, compared
      with patients without rejection (n = 37, P < 0.01 in all cases). Rejection
      diagnosis using gene expression criteria was possible 1 to 32 days before
      traditional diagnosis (median 11 days). High specificity was associated with IL
      18 expression (72%-93%), and high sensitivity was associated with perforin
      expression (63%-90%). Positive predictive value was optimized (78%-100%) by using
      combined up-regulation in both genes as a diagnostic criterion (double-positive).
      Using high expression in "either or both" genes as a diagnostic criterion yielded
      high sensitivity (82%-91%) and negative predictive value (91%-96%). CONCLUSIONS:
      Our data indicate that combined perforin and IL-18 gene expression measurements
      are useful tools for the recognition of graft rejection in its earliest stages.
      Serial measurements could be implemented as a monitoring system to identify
      patients at higher risk of rejection, making them candidates for biopsy or
      prophylactic increases in immunosuppression.

PMID- 15239628
TI  - Liver transplantation-induced antihistone H1 autoantibodies suppress mixed
      lymphocyte reaction.
AB  - BACKGROUND: In a rat model of orthotopic liver transplantation (OLT), recipient
      serum after OLT (post-OLT serum) has been reported to prevent allograft
      rejection. However, the molecular identities of immunosuppressive factors, which
      are in the early stage of post-OLT, remain elusive. This study was aimed to
      identify immunodominant suppressive factors present in early post-OLT serum.
      METHODS: The immunosuppressive activities of post-OLT serum, immunoglobulin (Ig)
      G-depleted serum, and purified IgG were evaluated in vitro by inhibition of the
      mixed lymphocyte reaction (MLR). Autoantigens recognized by the MLR-inhibitory
      IgG in early post-OLT serum were identified by the internal protein sequencing.
      RESULTS: Recipient post-OLT serum inhibited MLR, and its immunosuppressive
      activity vanished by means of the elimination of OLT-inducible IgG. IgG from post
      OLT sera (2-3 weeks) specifically reacted to 31-, 34-, and 73-kDa autoantigens on
      splenic cells. The internal sequences of the doublet 31- and 34-kDa antigens
      coincided completely with those of histone H1 molecules. The levels of histone H1
      specific antibodies were transiently increased to a plateau around 2 to 3 weeks
      after OLT but decreased in the later tolerogenic phase. Immunodepletion of
      antihistone H1 autoantibodies from early post-OLT serum abolished the MLR
      inhibitory activity. Furthermore, rabbit polyclonal antibody-directed histone H1
      not only suppressed MLR but also prolonged allograft survival. CONCLUSIONS: In
      this article, the authors provide evidence that autoreactive antibodies against
      histone H1, which are transiently induced at the early stage by liver
      transplantation, are a major OLT-induced graft survival factor.

PMID- 15239629
TI  - Detection of vimentin-specific autoreactive CD8+ T cells in cardiac transplant
      patients.
AB  - BACKGROUND: Evidence is emerging that autoimmunity can play a role in allograft
      rejection. Reports have described the presence of autoantibodies in transplant
      patients and CD4+ autoreactive T cells in rodent models of allograft rejection.
      The objective of this study was to seek evidence of CD8+ T-cell-mediated
      autoimmunity in the transplant setting. The author have previously observed
      autoimmunity to the non-polymorphic cytoskeletal protein vimentin in cardia
      transplant patients. In this study, vimentin antibody positive patients were
      screened for the presence of vimentin-specific self-major histocompatibility
      complex class I-restricted CD8+ T cells. METHODS: Two peptide sequences from
      vimentin that bound HLA-A*0201 were identified and fluorochrome-labeled A*0201
      tetramers with each peptide were constructed to screen for vimentin-specific T
      cells. RESULTS: Tetramer-binding CD8+ T cells were detected in peripheral blood
      lymphocytes from two of six patients after expansion by in vitro stimulation with
      peptide. Tetramer-binding T cells produced interferon-gamma in an antigen
      specific fashion. No autoreactive T cells specific for vimentin were detected
      after peptide stimulation of T cells from eight healthy A*0201-positive
      volunteers. CONCLUSIONS: This finding is the first evidence of CD8+ T-cell
      mediated autoimmunity in human transplant patients.

PMID- 15239631
TI  - One liver, three recipients: segment IV from split-liver procedures as a source
      of hepatocytes for cell transplantation.
AB  - Hepatocyte transplantation is emerging as a possible treatment for patients with
      acute liver failure and liver-based metabolic disorders. With the limited
      availability of donor tissue, it is important to find new sources of liver tissue
      for isolation of high-quality hepatocytes. Segment IV with or without the caudate
      lobe was removed during three split-liver procedures. Hepatocytes were isolated
      from the tissues using a collagenase perfusion technique under strict sterile
      conditions. The mean number of hepatocytes that were isolated was 5.14 x 10(8)
      cells with a mean cell viability of 89%. Two of the hepatocyte preparations were
      used for cell transplantation in a 1-day-old boy with an antenatal diagnosis of a
      severe urea cycle defect caused by ornithine transcarbamylase deficiency. The six
      recipients of split-liver grafts demonstrated no complications related to the
      removal of segment IV. Segment IV with or without the caudate lobe obtained from
      split-liver procedures is potentially a good source of high-quality hepatocytes
      for cell transplantation.

PMID- 15239630
TI  - Bcl-2 protection of islet allografts is unmasked by costimulation blockade.
AB  - One major limitation in pancreatic islet transplantation is availability of donor
      tissue. Donor shortage is exacerbated by islet apoptosis from the stresses of
      islet isolation and transplantation. Furthermore, the side effects of
      immunosuppressive drugs preclude transplants into patients whose diabetes is
      controlled by parenteral insulin. We hypothesised that over-expressing anti
      apoptotic Bcl-2 or secretion of immunomodulatory CTLA4Ig molecules in islet beta
      cells would enhance survival of transplanted islets while minimizing systemic
      side effects. Over-expression of Bcl-2 neither significantly increased
      preservation of islet cell mass after transplantation into immunocompromised
      recipients nor decreased cytokine-mediated apoptosis in vitro. Although Bcl-2
      over-expression alone was insufficient in protecting islet allografts from
      rejection, its beneficence was shown by the enhancement of protection when the
      adaptive immune response was inhibited by locally produced CTLA4Ig. Thus, the
      combination of anti-apoptotic and immunosuppressive intervention has additive or
      synergistic efficacy and may reduce the level of systemic immunosuppression or
      quantity of donor tissue required.

PMID- 15239632
TI  - Is severe intestinal chronic graft-versus-host disease an indication for surgery?
      A report of two cases.
AB  - Chronic graft-versus-host disease (cGVHD) frequently complicates allogeneic
      hematopoietic stem cell transplantation (HSCT), but small bowel involvement with
      obstruction is rarely observed. We report two patients who underwent allogeneic
      sibling HSCT and developed severe cGVHD involving the small bowel, causing
      unremitting obstructive symptoms and malnutrition despite maximal
      immunosuppression. Both patients underwent ileal resection and stricturoplasties.
      The first patient promptly improved, and remains asymptomatic 32 months after
      transplant. Three weeks after the resection of 90 cm of small bowel, the second
      patient developed leaking stricturoplasty and peritonitis, with a relapse of
      chronic myelogenous leukemia in accelerated phase. Later, an enterocutaneous
      fistula required additional small bowel resection and ileostomy. The patient
      subsequently died from pulmonary infection a few weeks after the last surgical
      procedure. Similar to inflammatory bowel disease, these two cases highlight that
      surgery may be a valuable option in patients who present with obstructive severe
      cGVHD refractory to aggressive immunosuppression.

PMID- 15239634
TI  - Mycoplasma hominis infection after liver transplantation in a child.

PMID- 15239633
TI  - C34T AMP deaminase 1 gene mutation protects cardiac function in donors.
AB  - Dysfunction of the donor heart is an important clinical problem that could be
      affected by genetic factors. We tested the hypothesis that possession of the C34T
      nonsense mutation in AMPD1 gene, which is known to improve survival in chronic
      heart failure, protects against cardiac dysfunction in donors. Genetic analysis
      for C34T mutation was performed by single-stranded conformational polymorphism
      (SSCP) in 22 donor hearts used for transplantation, 10 unused donor hearts with
      acute heart failure (HF), 37 patients with chronic HF, and 207 healthy controls.
      We found a significantly higher frequency of the mutation among donors with
      healthy hearts used for transplantation (31.8%) as compared to control population
      (13.5%, P < 0.001) and a lower frequency in dysfunctional donor hearts (5.0% P =
      0.025); the frequency of the C34T mutation in patients with chronic heart failure
      (14.8%) was not different from that of a control population. The presence of the
      C34T mutation in AMPD1 gene appears to be protective against acute heart failure
      in cardiac donors.

PMID- 15239635
TI  - 10-year tumor-free survival after intraoperative radiation therapy and secondary
      liver transplantation for hilar cholangiocarcinoma.

PMID- 15239636
TI  - Burn treatment.

PMID- 15239637
TI  - Why not lease your computers?

PMID- 15239638
TI  - Painless practice Rx: an extra patient, B.I.D.

PMID- 15239639
TI  - Not getting paid? Blame HIPAA.

PMID- 15239640
TI  - I knew she was trouble.

PMID- 15239641
TI  - My close call, your wake-up call.

PMID- 15239642
TI  - Coding for NP care.

PMID- 15239643
TI  - "He doesn't have age!".

PMID- 15239644
TI  - 9 things you should never say to a patient.

PMID- 15239645
TI  - Thank you, Dad.

PMID- 15239646
TI  - Malpractice. Can no-fault work?

PMID- 15239647
TI  - What to watch for in health plan contracts.

PMID- 15239648
TI  - Your liability for an NP's care.

PMID- 15239649
TI  - New, non-adenosine, high-potency agonists for the human adenosine A2B receptor
      with an improved selectivity profile compared to the reference agonist N
      ethylcarboxamidoadenosine.
AB  - The adenosine A(2B) receptor is the least well characterized of the four known
      adenosine receptor subtypes because of the absence of potent, selective agonists.
      Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4
      hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5-dicarbonitrile, 17,
      LUF5834, is a high-efficacy partial agonist with EC(50) = 12 nM and 45-fold
      selectivity over the adenosine A(3) receptor but lacking selectivity versus the
      A(1) and A(2A) subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a
      full agonist with EC(50) = 10 nM.

PMID- 15239650
TI  - N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of
      cyclin-dependent kinases 1 and 2.
AB  - The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor
      O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a
      structure-based drug discovery program resulting in the discovery of the potent
      CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and
      CDK2/cyclinA3, respectively). The SAR for this series have been explored further
      by the synthesis and evaluation of 45 N(2)-substituted analogues of NU2058. These
      studies have confirmed the requirement for the hydrogen bonding N(2)-NH group and
      the requirement for an aromatic N(2)-substituent to confer potency in the series.
      Additional potency is conferred by the presence of a group capable of donating a
      hydrogen bond at the 4'-position, for example, the 4'-hydroxy derivative (25,
      IC(50) = 94 nM and 69 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), 4'
      monomethylsulfonamide derivative (28, IC(50) = 9 nM and 7.0 nM vs CDK1/cyclinB
      and CDK2/cyclinA3, respectively), and 4'-carboxamide derivative (34, IC(50) = 67
      nM and 64 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). X-ray crystal
      structures have been obtained for key compounds and have been used to explain the
      observed trends in activity.

PMID- 15239651
TI  - A common pharmacophoric footprint for AIDS vaccine design.
AB  - The most promising target antigen for an HIV vaccine designed using the classic
      antibody strategy has been the viral coat protein gp120. Unfortunately, its high
      variability has prevented this approach. We examine here a 15-residue peptide
      derived from the CD4-binding domain of gp120. By use of molecular dynamics
      computer simulation, it is shown that despite considerable sequence variation,
      the three-dimensional structure of the peptide is preserved over the full range
      of clade-specific sequences. Furthermore, sequences threaded onto the structure
      exhibit common three-dimensional electrostatic and hydrophobic properties. These
      common physicochemical characteristics constitute a pharmacophoric footprint that
      promises to be useful in the design of a synthetic antigen for vaccine
      development.

PMID- 15239652
TI  - Structure-based design, synthesis, and structure-activity relationship studies of
      novel non-nucleoside adenosine deaminase inhibitors.
AB  - We disclose herein optimization efforts around the novel, highly potent non
      nucleoside adenosine deaminase (ADA) inhibitor, 1-[(R)-1-hydroxy-4-(6-(3-(1
      methylbenzimidazol-2-yl)propionylamino)indol-1-yl)-2-butyl]imidazole-4
      carboxamide 1 (K(i)= 7.7 nM), which we recently reported. Structure-based drug
      design (SBDD) utilizing the crystal structure of the 1/ADA complex was performed
      in order to obtain structure-activity relationships (SAR) for this type of
      compound rationally and effectively. To utilize the newly formed hydrophobic
      space (F2), replacement of the benzimidazole ring of 1 with a n-propyl chain (4b)
      or a simple phenyl ring (4c) was tolerated in terms of binding activity, and the
      length of the methylene-spacer was shown to be optimal at two or three.
      Replacement of an amide with an ether as a linker was also well tolerated in
      terms of binding activity and moreover improved the oral absorption (6a and 6b).
      Finally, transformation of indol-1-yl to indol-3-yl resulted in discovery of a
      novel highly potent and orally bioavailable ADA inhibitor, 1-[(R)-4-(5-(3-(4
      chlorophenyl)propoxy)-1-methylindol-3-yl)-1-hydroxy-2-butyl]imidazole-4
      carboxamide 8c.

PMID- 15239653
TI  - Pyridinium cationic lipids in gene delivery: a structure-activity correlation
      study.
AB  - Three series of pyridinium cationic lipids useful as nonviral gene delivery
      agents were prepared by reaction of pyrylium salts with aminodiols, followed by
      acylation with fatty acyl chlorides. On the basis of this set of compounds, we
      undertook a comprehensive structure-activity relationship study at the level of
      the linker, hydrophobic anchor, and counterion in order to identify the
      structural elements that generate the highest transfection efficiency for this
      new type of cationic lipid. The results revealed that when formulated with
      cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6
      trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride
      (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies
      surpassing classic DOTAP-based formulations and with lower cytotoxicity.
      Subsequent tests on other malignancies yielded similarly promising results.

PMID- 15239654
TI  - Rational design of new antituberculosis agents: receptor-independent four
      dimensional quantitative structure-activity relationship analysis of a set of
      isoniazid derivatives.
AB  - A 4D-QSAR analysis was carried out for a set of 37 hydrazides whose minimum
      inhibitory concentrations against M. tuberculosis var. bovis were evaluated.
      These ligands are thought to act like isoniazid in mycolic acid biosynthesis.
      Results indicate that nonpolar groups in the acyl moiety of ligands markedly
      decrease biological activity. Molecular modifications of the ligand NAD moiety,
      including nonpolar groups and hydrogen bond donor and acceptor groups, seemingly
      improve ligand interactions with amino acid residues of the InhA active site.

PMID- 15239655
TI  - A ligand-based approach to identify quantitative structure-activity relationships
      for the androgen receptor.
AB  - We examined the three-dimensional quantitative structure-activity relationship
      (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor
      (AR) using comparative molecular field analysis (CoMFA). The goal of these
      studies was to identify structural features necessary for high binding affinity
      and optimization of selective androgen receptor modulators (SARMs). A homology
      model of the AR was used as a scaffold to align six lead compounds that served as
      templates for alignment of the remaining 116 structures prior to CoMFA modeling.
      The conventional r(2) and cross-validated q(2) relating observed and predicted
      relative binding affinity (RBA) were 0.949 and 0.593, respectively. Comparison of
      predicted and observed RBA for a test set of 10 compounds resulted in an r(2) of
      0.954, demonstrating the excellent predictive ability of the model. These
      integrated homology modeling and CoMFA studies identified critical amino acids
      for SARM interactions and provided QSAR data as the basis for mechanistic studies
      of AR structure, function, and design of optimized SARMs.

PMID- 15239656
TI  - Pruned receptor surface models and pharmacophores for three-dimensional database
      searching.
AB  - A pharmacophore represents the 3D arrangement of chemical features that are
      shared by molecules exhibiting activity at a protein receptor. Pharmacophores are
      routinely used in 3D database searching for identifying potential lead compounds.
      The lack of shape constraints causes the query to identify compounds that could
      not fit into the active site. In the absence of structural information, a
      receptor surface model (RSM) can be used to represent the active site. The RSM
      consists of a surface that envelops a set of known actives after these have been
      aligned using their common features. When used for database searching, a RSM is
      overconstraining as it restricts access to regions that could be occupied by
      ligands, such as the solvent-protein interface or unexplored pockets. We describe
      a protocol for developing pruned RSMs using information gleaned from 3D
      quantitative structure-activity relationship (QSAR) models. We examined the
      performance of queries that consist of pharmacophores used alone or with pruned
      or unpruned RSMs by performing searches on six databases containing known actives
      distributed among inactives. The pruned RSMs yield an average selectivity 1.8
      times greater than that for pharmacophore queries, compared to 1.6 times for
      unpruned RSMs. However, the pruned RSMs retrieve on average 73% of the actives
      identified using the pharmacophores, compared to 40% for the unpruned RSMs. As
      such, pruned RSMs represent a useful compromise between the high sensitivity of
      pharmacophores and the high selectivity of unpruned RSMs.

PMID- 15239657
TI  - Novel azapeptide inhibitors of hepatitis C virus serine protease.
AB  - Azapeptides are known inhibitors of several serine and cysteine proteases. In
      seeking different classes of inhibitors for the HCV serine protease, a series of
      novel azapeptide-based inhibitors were investigated which incorporated
      noncleavable P1/P1' aza-amino acyl residues. Extensive SAR studies around the
      P1/P1' aza-amino acyl fragment resulted in the identification of potent and
      selective inhibitors. Using NMR studies, we have shown that this series of
      inhibitors bind in a noncovalent competitive fashion to the NS3 protease active
      site. The bound conformation of one of these new azapeptide-based inhibitors was
      determined using the transfer NOE technique. Incorporation of these new aza-amino
      acyl functionalities in the P1 position provided a handle to probe for new
      interactions in the S' region of the enzyme.

PMID- 15239659
TI  - PDBLIG: classification of small molecular protein binding in the Protein Data
      Bank.
AB  - It is known that proteins can adopt different folds while sharing similar
      features for recognition of similar substrates or ligands, for example, in the
      binding sites of enzyme cofactors such as ATP. On the other hand, proteins that
      have highly flexible binding sites or belong to large and diverse protein
      families can bind structurally dissimilar ligands, as, for example, in the case
      of the matrix metalloprotease family. We have developed a database, PDBLIG, that
      classifies protein domains and ligands. The information stored includes each
      protein's function, domain class(es), which ligand(s) it binds, and so on. The
      database can provide valuable knowledge for drug discovery, supporting the
      answering of questions such as whether the same drug molecule can bind different
      target protein families and whether these families are related functionally or
      structurally, which ligand classes (such as metabolites or organic molecules)
      bind to a particular protein family and whether the ligands are druglike, and
      which target families bind a wide variety of ligands and whether different
      ligands are associated with different subfamilies.

PMID- 15239658
TI  - Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.
AB  - Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3),
      and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6.
      In the 1960s, the oxidized product 4 had been assigned a para-quinone structure,
      which was later modified to an ortho-quinone. To distinguish between the two
      possible quinone structures, a detailed NMR investigation was undertaken. The
      original para-quinone structure was confirmed. X-ray crystallography elucidated
      the structures of the crystalline 2 and 6. All three compounds displayed
      antiproliferative activity in several human cancer cell lines in vitro, and
      quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.

PMID- 15239660
TI  - Novel S-substituted aminoalkylamino ethanethiols as potential antidotes against
      sulfur mustard toxicity.
AB  - Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory
      treatment regimen is not yet available for this toxicant. In a search for an
      effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl
      alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky,
      alicyclic, aryl, and heterocyclic substituents, have been designed and
      synthesized as candidate antidotes against SM toxicity. These compounds were
      screened for their protective efficacy through the oral route against dermally
      applied sulfur mustard in female mice measured on the basis of percent survival
      following percutaneous administration of SM. A number of compounds demonstrated
      significant protection.

PMID- 15239661
TI  - Studies toward the discovery of the next generation of antidepressants. 3. Dual 5
      HT1A and serotonin transporter affinity within a class of N
      aryloxyethylindolylalkylamines.
AB  - N-aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT(1A)
      affinity are described. These compounds represent truncated analogues of our
      previously reported piperidinyl derivatives (3). Compounds in this investigation
      were found to have more similar affinities and functional activities for the 5
      HT(1A) receptor and 5-HT transporter. Though 5-HT(1A) antagonism is not
      consistently observed throughout series 5, several molecular features were found
      to be essential to obtain high and balanced activities. The proper placement of a
      heteroatom in the aryl ring and the length of the linkage used to tether the
      indole moiety had significant influence on 5-HT(1A) and 5-HT transporter
      affinities. Introduction of a halogen into the aryl ring usually lowered
      intrinsic activity and in some cases led to full 5-HT(1A) antagonists. Compounds
      33 and 34 were observed to be full 5-HT(1A) antagonists with K(i) values of
      approximately 30 nM for the 5-HT(1A) receptor and K(i) values of 5 and 0.5 nM for
      the 5-HT transporter, respectively. Unfortunately, similar to our previous series
      (3), compounds in this report also had high affinity for the alpha(1) receptor.

PMID- 15239662
TI  - Sulfonyl-containing aldophosphamide analogues as novel anticancer prodrugs
      targeted against cyclophosphamide-resistant tumor cell lines.
AB  - A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were
      synthesized as potential anticancer prodrugs that liberate the cytotoxic
      phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a
      nonenzymatic activation mechanism. Kinetic studies demonstrated that all these
      compounds spontaneously liberate phosphoramide mustards with half-lives in the
      range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate
      buffer at pH 7.4 and 37 degrees C. Analogous to Aldo, the rates of beta
      elimination in all compounds was enhanced in reconstituted human plasma under
      same conditions. The compounds were more potent than the corresponding
      phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro
      (IC(50) = 1.8-69.1 microM). Several compounds showed excellent in vivo antitumor
      activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant)
      tumor cell lines.

PMID- 15239663
TI  - Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a
      dopaminergic agent with a novel mode of action for the potential treatment of
      erectile dysfunction.
AB  - A new class of agents with potential utility for the treatment of erectile
      dysfunction has been discovered, guided by the hypothesis that selective D4
      agonists are erectogenic but devoid of the side effects typically associated with
      dopaminergic agents. The lead agent 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H
      benzimidazole (1, ABT-724) was discovered by optimization of a series of
      benzimidazole arylpiperazines. This highly selective D4 agonist was found to be
      very potent and efficacious in vivo, eliciting penile erections in rats at a dose
      of 0.03 micromol/kg, with a positive response rate of 77% erectile incidence.
      Even at high doses, it was devoid of side effects in animal models of central
      nervous system behaviors, emesis, or nausea. The structure-activity relationship
      of the parent benzimidazole series leading to 1 is described, with the detailed
      in vitro and in vivo profiles described. Distinctive structural features were
      discovered that are associated with D4 selective agonism in this series of
      analogues.

PMID- 15239665
TI  - Synthesis and biological evaluation of 2-phenylpyran-4-ones: a new class of
      orally active cyclooxygenase-2 inhibitors.
AB  - A series of 2-phenylpyran-4-ones were prepared and evaluated for their ability to
      inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work
      was carried out within this series, and a number of potent and selective COX-2
      inhibitors were identified. Compounds having a p-methylsulfone group at the 2
      phenyl ring showed the best COX-2 inhibitory activity. The introduction of a
      substituted phenoxy ring at position 3 enhanced both the in vitro and in vivo
      activity within the series. A selected group of 3-phenoxypyran-4-ones exhibited
      excellent activity in an experimental model of pyresis. The in vivo
      antiinflammatory activity of these compounds was confirmed with the evaluation of
      their antiarthritic and analgesic effectiveness. Moreover, their pharmacokinetic
      profile in rats is compatible with a once a day administration by oral route in
      humans. Within this novel series, compounds 21, 31, 34, and 35 have been selected
      for further preclinical and clinical evaluation.

PMID- 15239664
TI  - Synthesis and biological evaluation of a new class of geldanamycin derivatives as
      potent inhibitors of Hsp90.
AB  - The heat shock protein Hsp90 has increasingly become an important therapeutic
      target especially for treatment of cancers. Inhibition of the ATPase activity of
      Hsp90 by natural products (e.g., 17-allylaminogeldanamycin or radicicol) leads to
      the ubiquitination of oncogenic client proteins such as Her-2, Raf-1, and p-Akt
      followed by their proteasomal degradation. Hsp90 inhibitors simultaneously target
      multiple oncogenic proteins and provide an advantage for cancer therapy due to
      the potential for increased efficacy and overcoming drug resistance. In an effort
      to convert geldanamycin into a druglike compound with better pharmacokinetic
      properties and efficacy in human tumor xenograft models, geldanamycin was
      derivatized on the 17-position to prepare new analogues such as 17-geldanamycin
      amides, carbamates, and ureas and 17-arylgeldanamycins. All the compounds were
      first evaluated ex vivo using a cell-based Her-2 degradation assay and in vitro
      using biochemical assays that measure recombinant Hsp90 (rHsp90) competitive
      binding and changes in rHsp90 conformation. In addition, we confirmed the
      selectivity of geldanamycin analogues for Hsp90 derived from tumor cells using a
      novel cell lysate binding assay.

PMID- 15239666
TI  - 2-amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine
      DNA alkyltransferase.
AB  - 2-amino-O4-benzylpteridine (1), 2-amino-O4-benzyl-6,7-dimethylpteridine (2), 2
      amino-O4-benzyl-6-hydroxymethylpteridine (4), 2-amino-O4-benzylpteridine-6
      carboxylic acid (5), 2-amino-O4-benzyl-6-formylpteridine (6), and O4-benzylfolic
      acid (7) are shown to be as potent or more potent inactivators of the human DNA
      repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) in vitro
      than O6-benzylguanine, the prototype alkyltransferase inactivator currently in
      clinical trials. Additionally, the negatively charged (at physiological pH)
      inactivators 2-amino-O4-benzylpteridine-6-carboxylic acid (5) and O4-benzylfolate
      (7) are far more water soluble than O6-benzylguanine. The activity of O4
      benzylfolic acid (7) is particularly noteworthy because it is roughly 30 times
      more active than O6-benzylguanine against the wild-type alkyltransferase and is
      even capable of inactivating the P140K mutant alkyltransferase that is resistant
      to inactivation by O6-benzylguanine. All the pteridine derivatives except 2-amino
      O4-benzylpteridine-6-carboxylic acid are effective in enhancing cell killing by
      1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the effectiveness of O4
      benzylfolate as an adjuvant for cell killing by BCNU appears to be a function of
      a cell's alpha-folate receptor expression. Thus, O4-benzylfolate is least
      effective as an adjuvant in A549 cells (which express little if any receptor), is
      moderately effective in HT29 cells (which express low levels of the receptor),
      but is very effective in KB cells (which are known to express high levels of the
      alpha-folate receptor). Therefore, O4-benzylfolic acid shows promise as an agent
      for possible tumor-selective alkyltransferase inactivation, which suggests it may
      prove to be superior to O6-benzylguanine as a chemotherapy adjuvant.

PMID- 15239667
TI  - Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126)
      active in vitro against HIV-1 wild type and variants carrying non-nucleoside
      reverse transcriptase inhibitor resistance mutations.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) active against NNRTI
      resistant mutants were obtained by introducing two methyl groups at positions 3
      and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three
      glycinamide/alaninamide units to its carboxyamide function. In cell-based assays,
      the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant
      mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly
      resistant to efavirenz] superior to that of the parent indole derivative 1.

PMID- 15239668
TI  - RLP, a novel Ras-like protein, is an immediate-early transforming growth factor
      beta (TGF-beta) target gene that negatively regulates transcriptional activity
      induced by TGF-beta.
AB  - We have described previously the use of microarray technology to identify novel
      target genes of TGF-beta (transforming growth factor-beta) signalling in mouse
      embryo fibroblasts deficient in Smad2 or Smad3 [Yang, Piek, Zavadil, Liang, Xie,
      Heyer, Pavlidis, Kucherlapati, Roberts and Bottinger (2003) Proc. Natl. Acad.
      Sci. U.S.A. 100, 10269-10274]. Among the TGF-beta target genes identified, a
      novel gene with sequence homology to members of the Ras superfamily was
      identified, which we have designated as RLP (Ras-like protein). RLP is a Smad3
      dependent immediate-early TGF-beta target gene, its expression being induced
      within 45 min. Bone morphogenetic proteins also induce expression of RLP, whereas
      epidermal growth factor and phorbol ester PMA suppress TGF-beta-induced
      expression of RLP. Northern-blot analysis revealed that RLP was strongly
      expressed in heart, brain and kidney, and below the detection level in spleen and
      skeletal muscles. At the protein level, RLP is approx. 30% homologous with
      members of the Ras superfamily, particularly in domains characteristic for small
      GTPases. However, compared with prototypic Ras, RLP contains a modified P-loop,
      lacks the consensus G2 loop and the C-terminal prenylation site and harbours
      amino acid substitutions at positions that render prototypic Ras oncogenic.
      However, RLP does not have transforming activity, does not affect phosphorylation
      of mitogen-activated protein kinase and is unable to bind GTP or GDP. RLP was
      found to associate with certain subtypes of the TGF-beta receptor family, raising
      the possibility that RLP plays a role in TGF-beta signal transduction. Although
      RLP did not interact with Smads and did not affect TGF-beta receptor-induced
      Smad2 phosphorylation, it inhibited TGF-beta-induced transcriptional reporter
      activation, suggesting that it is a novel negative regulator of TGF-beta
      signalling.

PMID- 15239669
TI  - Copper homoeostasis in Drosophila melanogaster S2 cells.
AB  - Copper homoeostasis was investigated in the Drosophila melanogaster S2 cell line
      to develop an insect model for the study of copper regulation. Real-time PCR
      studies have demonstrated expression in S2 cells of putative orthologues of human
      Cu regulatory genes involved in the uptake, transport, sequestration and efflux
      of Cu. Drosophila orthologues of the mammalian Cu chaperones, ATOX1 (a human
      orthologue of yeast ATX1), CCS (copper chaperone for superoxide dismutase), COX17
      (a human orthologue of yeast COX17), and SCO1 and SCO2, did not significantly
      respond transcriptionally to increased Cu levels, whereas MtnA, MtnB and MtnD
      (Drosophila orthologues of human metallothioneins) were up-regulated by Cu in a
      time- and dose-dependent manner. To examine the effect on Cu homoeostasis,
      expression of several key copper homoeostasis genes was suppressed using double
      stranded RNA interference. Suppression of the MTF-1 (metal-regulatory
      transcription factor 1), reduced both basal and Cu-induced gene expressions of
      MtnA, MtnB and MtnD, significantly reducing the tolerance of these cells to
      increased Cu. Suppression of either Ctr1A (a Drosophila orthologue of yeast CTR1)
      or Ctr1B significantly reduced Cu uptake from media, demonstrating that both
      these proteins function to transport Cu into S2 cells. Significantly, Cu induced
      Ctr1B gene expression, and this could be prevented by suppressing MTF-1,
      suggesting that Ctr1B might be involved in Cu detoxification. Suppression of
      DmATP7, the putative homologue of human Cu transporter genes ATP7A and ATP7B,
      significantly increased Cu accumulation, demonstrating that DmATP7 is essential
      for efflux of excess Cu. This work is consistent with previous studies in
      mammalian cells, validating S2 cells as a model system for studying Cu transport
      and identifying novel Cu regulatory mechanisms.

PMID- 15239670
TI  - Disruption of dimerization and substrate phosphorylation inhibit factor
      inhibiting hypoxia-inducible factor (FIH) activity.
AB  - HIF (hypoxia-inducible factor) is an alphabeta transcription factor that
      modulates the hypoxic response in many animals. The cellular abundance and
      activity of HIF-alpha are regulated by its post-translational hydroxylation. The
      hydroxylation of HIF is catalysed by PHD (prolyl hydroxylase domain) enzymes and
      FIH (factorinhibiting HIF), all of which are 2-oxoglutarate- and Fe(II)-dependent
      dioxygenases. FIH hydroxylates a conserved asparagine residue in HIF-alpha (Asn
      803), which blocks the binding of HIF to the transcriptional co-activator p300,
      preventing transcription of hypoxia-regulated genes under normoxic conditions. In
      the present paper, we report studies on possible mechanisms for the regulation of
      FIH activity. Recently solved crystal structures of FIH indicate that it is
      homodimeric. Site-directed mutants of FIH at residues Leu-340 and Ile-344,
      designed to disrupt dimerization, were generated in order to examine the
      importance of the dimeric state in determining FIH activity. A single point
      mutant, L340R (Leu-340-->Arg), was shown to be predominantly monomeric and to
      have lost catalytic activity as measured by assays monitoring 2-oxoglutarate
      turnover and asparagine hydroxylation. In contrast, the I344R (Ile-344-->Arg)
      mutant was predominantly dimeric and catalytically active. The results imply that
      the homodimeric form of FIH is required for productive substrate binding. The
      structural data also revealed a hydrophobic interaction formed between FIH and a
      conserved leucine residue (Leu-795) on the HIF substrate, which is close to the
      dimer interface. A recent report has revealed that phosphorylation of Thr-796,
      which is adjacent to Leu-795, enhances the transcriptional response in hypoxia.
      Consistent with this, we show that phosphorylation of Thr-796 prevents the
      hydroxylation of Asn-803 by FIH.

PMID- 15239671
TI  - Phosphorylation of androgen receptor isoforms.
AB  - Phosphorylation of the human AR (androgen receptor) is directly correlated with
      the appearance of at least three AR isoforms on an SDS/polyacrylamide gel.
      However, it is still not clear to what extent phosphorylation is involved in the
      occurrence of isoforms, which sites are phosphorylated and what are the functions
      of these phosphosites. The human AR was expressed in COS-1 cells and AR
      phosphorylation was studied further by mutational analyses and by using reversed
      phase HPLC and MS. The reversed-phase HPLC elution pattern of the three isoforms
      revealed that Ser-650 was phosphorylated constitutively. After de novo synthesis,
      only Ser-650 was phosphorylated in the smallest isoform of 110 kDa and both Ser
      650 and Ser-94 were phosphorylated in the second isoform of 112 kDa. The hormone
      induced 114 kDa isoform shows an overall increase in phosphorylation of all the
      isolated peptides. The activities of the Ser-Ala substitution mutant S650A (Ser
      650-->Ala) was found to be identical with wild-type AR activation in four
      different cell lines and three different functional analyses, e.g.
      transactivation, N- and C-terminal-domain interaction and co-activation by
      transcriptional intermediary factor 2. This was also found for mutants S94A and
      S515A with respect to transactivation. However, the S515A mutation, which should
      eliminate phosphorylation of the potential mitogen-activated protein kinase site,
      Ser-515, resulted in an unphosphorylated form of the peptide containing Ser-650.
      This suggests that Ser-515 can modulate phosphorylation at another site. The
      present study shows that the AR isoform pattern from AR de novo synthesis is
      directly linked to differential phosphorylation of a distinct set of sites. After
      mutagenesis of these sites, no major change in functional activity of the AR was
      observed.

PMID- 15239672
TI  - Transient kinetics of the reaction catalysed by magnesium protoporphyrin IX
      methyltransferase.
AB  - Magnesium protoporphyrin IX methyltransferase (ChlM), an enzyme in the
      chlorophyll biosynthetic pathway, catalyses the transfer of a methyl group to
      magnesium protoporphyrin IX (MgP) to form magnesium protoporphyrin IX monomethyl
      ester (MgPME). S-Adenosyl-L-methionine is the other substrate, from which a
      methyl group is transferred to the propionate group on ring C of the porphyrin
      macrocycle. Stopped-flow techniques were used to characterize the binding of
      porphyrin substrate to ChlM from Synechocystis PCC6803 by monitoring tryptophan
      fluorescence quenching on a millisecond timescale. We concluded that a rapid
      binding step is preceded by a slower isomerization of the enzyme. Quenched-flow
      techniques have been employed to characterize subsequent partial reactions in the
      catalytic mechanism. A lag phase has been identified that has been attributed to
      the formation of an intermediate. Our results provide a greater understanding of
      this catalytic process which controls the relative concentrations of MgP and
      MgPME, both of which are implicated in signalling between the plastid and nucleus
      in plants.

PMID- 15239674
TI  - Optimization of penicillin G acylase multipoint immobilization on to
      glutaraldehyde-chitosan beads.
AB  - The objective of this work was to study the immobilization of penicillin G
      acylase from Escherichia coli on to chitosan-glutaraldehyde beads by multipoint
      covalent binding. This process was optimized using a 2(3) experimental design.
      The parameters selected for the present study were the concentrations of
      glutaraldehyde, phenylacetic acid and sodium borohydride. Three responses were
      chosen, namely immobilization yield and stabilization factors of enzyme
      derivatives at high temperature and at alkaline pH. All the runs at the maximum
      (+1) and minimum (-1) levels were performed at random. Three experiments were
      performed at the centre point, coded as zero, for experimental-error estimation.
      With respect to immobilization yield, the main effectors were the concentrations
      of glutaraldehyde and phenylacetic acid. For stabilization factors at 50 degrees
      C and at alkaline pH, the main effectors were the concentrations of
      glutaraldehyde and sodium borohydride and the interaction between them.

PMID- 15239675
TI  - Laser-capture microdissection: applications in routine molecular
      dermatopathology.
AB  - Advances in molecular pathology with the introduction of the Southern blot
      technique and the polymerase chain reaction (PCR) have emerged as important
      tools, which are frequently used in routine dermato-histopathology. Applications
      for PCR-based diagnostics are particularly helpful for the determination of
      clonality in cutaneous lymphocytic infiltrates and for detection of infectious
      agents, such as herpes simplex virus (HSV), varicella zoster virus (VZV),
      Borrelia burgdorferi, Mycobacteria, Leishmania, and Treponema pallidum. As
      biopsies are always composed of different cells, the cells of interest are often
      only a minor population. As a consequence, their specific DNA is diluted by the
      majority of contaminating cells. Another problem is the time- and labor-intensive
      DNA extraction, because usually only formalin-fixed, paraffin-embedded tissue is
      available, which makes molecular diagnostics a time and labor consuming, and
      consequently a cost-intensive procedure. To overcome these shortcomings and to
      eventually shorten the time to generate a result, we introduce a laser-capture
      microdissection (LCM)-based method for the detection of infectious agents and
      clonality. Only the cells of interest for the particular indication are
      microdissected (e.g. epidermal cells for HSV and VZV and lymphocytes for
      clonality analysis) and subjected to PCR amplification. Due to an accelerated DNA
      extraction procedure which generates DNA in 5 h (compared to 3-4 days using
      conventional DNA extraction), we are able to generate a result within one working
      day.

PMID- 15239673
TI  - Myristoylated alanine-rich C kinase substrate (MARCKS) is involved in myoblast
      fusion through its regulation by protein kinase Calpha and calpain proteolytic
      cleavage.
AB  - MARCKS (myristoylated alanine-rich C kinase substrate) is a major cytoskeletal
      protein substrate of PKC (protein kinase C) whose cellular functions are still
      unclear. However numerous studies have implicated MARCKS in the stabilization of
      cytoskeletal structures during cell differentiation. The present study was
      performed to investigate the potential role of Ca(2+)-dependent proteinases
      (calpains) during myogenesis via proteolysis of MARCKS. It was first demonstrated
      that MARCKS is a calpain substrate in vitro. Then, the subcellular expression of
      MARCKS was examined during the myogenesis process. Under such conditions, there
      was a significant decrease in MARCKS expression associated with the appearance of
      a 55 kDa proteolytic fragment at the time of intense fusion. The addition of
      calpastatin peptide, a specific calpain inhibitor, induced a significant decrease
      in the appearance of this fragment. Interestingly, MARCKS proteolysis was
      dependent of its phosphorylation by the conventional PKCalpha. Finally, ectopic
      expression of MARCKS significantly decreased the myoblast fusion process, while
      reduced expression of the protein with antisense oligonucleotides increased the
      fusion. Altogether, these data demonstrate that MARCKS proteolysis is necessary
      for the fusion of myoblasts and that cleavage of the protein by calpains is
      involved in this regulation.

PMID- 15239676
TI  - K16 expression in uninvolved psoriatic skin: a possible marker of pre-clinical
      psoriasis.
AB  - BACKGROUND: K16, a type I keratin, is upregulated in hyperproliferative states
      including psoriasis. It has been used as a marker of psoriasis and its expression
      is upregulated in relapsing psoriasis and downregulating in resolving. We
      evaluated non-lesional psoriatic skin for K16 expression. METHODS: Sixty-seven
      non-lesional and lesional skin samples from patients with psoriasis and normal
      skin from 19 non-psoriatic patients were studied by immunohistochemistry on
      frozen sections with K16. RESULTS: Seventeen of 19 normal skin samples showed
      staining of basal cells in the deeper part of the rete ridges. Sixty-two non
      lesional psoriatic skin samples showed intense basal staining of K16. Of the
      remaining five non-lesional samples, diffuse intense suprabasal staining in one,
      pan-epidermal staining in two, and no staining was seen in two samples.
      Suprabasal (37), diffuse (14), sandwich (12), and basal (3) pattern staining were
      seen in psoriatic skin. One psoriatic skin sample did not show any expression.
      CONCLUSION: Our results demonstrate that K16 expression is also observed in non
      lesional psoriatic skin and may serve as a marker of preclinical psoriasis.

PMID- 15239677
TI  - Hypoxia regulation of the cell cycle in malignant melanoma: putative role for the
      cyclin-dependent kinase inhibitor p27.
AB  - BACKGROUND: Intratumor hypoxia has been shown to promote more aggressive and
      metastatic cancer phenotypes that are associated with treatment resistance and
      poor prognosis. Cellular proliferation and its control are known to be important
      components of tumor progression. Hypoxia induces cell-cycle arrest in cultured
      cell lines, possibly via up-regulation of the cyclin-dependent kinase inhibitor
      p27. The effect of hypoxia on cell-cycle regulation in excised human tumors has
      not been investigated. METHODS: We performed immunohistochemistry for p27 and Ki
      67 on 10 formalin-fixed paraffin-embedded metastatic melanomas, selected on the
      basis of histological evidence of zonal/geographic necrosis, adjacent to areas
      with viable perivascular tumor cells. RESULTS: In the majority of cases, there
      was a significant increase in p27 staining in cells adjacent to necrotic areas
      compared to perivascular zones. An inverse staining pattern between Ki-67 and p27
      was identified in these tumors. Tumors with no zonal increase in p27 staining
      demonstrated a diffuse pattern of staining for Ki-67 within tumor nests.
      CONCLUSIONS: While increased cellular proliferation is a characteristic of
      cancer, subsets of human melanomas may retain the ability to regulate their rate
      of proliferation in response to changes in the tumor microenvironment. The
      hypoxia-mediated cell-cycle arrest (decreased Ki-67) in these tumors may be
      mediated by p27 up-regulation.

PMID- 15239678
TI  - Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary
      Paget's disease.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of
      apocrine gland bearing skin characterized by intraepidermal proliferation of
      adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to
      migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP)
      enzymes have been implicated in both of these processes in other types of skin
      cancer. METHODS: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and
      MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27
      EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5)
      and tenascin-C, two extracellular matrix proteins associated with tumor invasion,
      was studied by immunohistochemistry. RESULTS: MMP-7 (matrilysin-1) and MMP-19
      were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP
      2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5
      and tenascin-C positivity did not correlate with the level of invasion. MMP-7,
      MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent.
      CONCLUSIONS: MMP expression did not generally associate with the level of
      invasion of EMPD. In three samples positive for MMP-7 and four samples positive
      for MMP-19, an underlying carcinoma was detected, suggesting the importance of
      these two MMPs as predictors of secondary EMPD or the putative origin of Paget's
      cells from the dermal adenocarcinoma cells of apocrine duct origin.

PMID- 15239679
TI  - Neurofibromatous changes in dermatofibrosarcoma protuberans: a potential pitfall
      in the diagnosis of a serious cutaneous soft tissue neoplasm.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant
      neoplasm that has the potential for aggressive local growth and destruction if
      not treated appropriately. Although the storiform arrangement of spindle cells in
      DFSP is relatively characteristic, histologic patterns simulating other benign as
      well as malignant neoplasms such as dermatofibroma, neurofibroma, malignant
      fibrous histiocytoma, and atypical fibroxanthoma have been described. METHODS: We
      collected and analyzed six cases of probable DFSP in which a specific diagnosis
      could not be rendered due to the predominant neurofibromatous changes in the
      histologic sections. In an attempt to reach a definitive diagnosis, the clinical
      history and physical characteristics of the lesions were taken into account, and
      all cases were further evaluated using immunostaining for CD34 and S-100 protein.
      RESULTS: The average age of the patient was 56 years (range 21-80), and the male
      to female ratio was 1 : 1. The location of lesions included the scalp, neck,
      back, and abdomen. All cases displayed two distinct histological patterns: (i) a
      proliferation of spindle cells with wavy nuclei in a loose mucinous stroma
      suggesting neural differentiation and (ii) a proliferation of spindle cells which
      interweaved and filled the reticular dermis extending into the subcutis. The wide
      variety of clinical impressions and descriptions indicated that the diagnoses
      were not always straightforward, and clinical information did not always assist
      in the clinicopathologic correlation. All lesions stained positively for CD34;
      however, three of six cases also stained positively for S-100. The three cases
      which were CD34 positive and S-100 negative were likely DFSP, and this was the
      final diagnosis given. The three cases that were CD34 and S-100 positive did not
      allow for a straightforward diagnosis. CONCLUSIONS: DFSP may demonstrate areas
      with features more characteristic of a benign neural lesion, such as a
      neurofibroma, which can lead to underdiagnosis and subsequent failure to treat.
      Clinicians and pathologists should recognize this potential diagnostic pitfall
      and understand that equivocal clinical information, combined with non-specific
      immunohistochemical staining patterns, can further complicate the dilemma. In
      these situations, where DFSP is the likely diagnosis but definitive evidence
      cannot be obtained, full excision of the lesion should be recommended to avoid
      mistreatment of a potentially malignant lesion.

PMID- 15239680
TI  - Pleural mesothelioma with cutaneous extension to chest wall scars.
AB  - BACKGROUND: Cutaneous mesothelioma is rare but may occur following local surgical
      procedures for visceral mesothelioma or as a metastasis. METHODS: A patient with
      pleural mesothelioma, who developed papules within chest wall scars, 14 and 15
      months after pleural biopsy and thoracentesis, respectively, is reported.
      RESULTS: Histopathology showed an epithelioid tumor forming tubulopapillary and
      glandular structures. The diagnosis of mesothelioma was confirmed with
      immunohistochemistry. Tumor cells stained characteristically for low-molecular
      weight cytokeratins 5/6, calretinin, and vimentin and were negative for
      mucicarmine, carcinoembryonic antigen, thyroid transcription factor 1, prostate
      specific antigen, gross cystic disease fluid protein, S-100, factor VIII, and
      CD31. CONCLUSIONS: Histologically, mesothelioma may resemble a primary adnexal
      neoplasm, metastatic adenocarcinoma, or angiosarcoma. Immunohistochemistry can
      clarify the diagnosis. Clinicians should be aware of the varied presentations of
      mesothelioma, as cutaneous presentations are becoming increasingly common.

PMID- 15239681
TI  - Linear nevus comedonicus with epidermolytic hyperkeratosis.
AB  - BACKGROUND: Nevus comedonicus (NC) is rarely associated with the histopathologic
      pattern of follicular epidermolytic hyperkeratosis (EHK). We found eight cases
      reported. In one case, the condition was transmitted to the offspring in the form
      of generalized EHK. METHODS: We describe a case of linear NC with EHK in a 46
      year-old woman. RESULTS: Histopathologic examination revealed the typical
      features of NC. Additionally, the follicular epithelial walls showed EHK with
      characteristic perinuclear vacuolization in the stratum spinosum and stratum
      granulosum and large, irregular keratohyalin granules in the granular cell layer.
      CONCLUSIONS: The clinical and histopathologic features of this case are
      consistent with a diagnosis of linear NC with EHK. Lesions of NC suspected by
      clinical exam should be examined microscopically to look for features of EHK. If
      present, patients should be educated about the risk, albeit rare, of passing on a
      more severe form of the disorder to subsequent generations.

PMID- 15239682
TI  - Phakomatous choristoma of the eyelid: a report of a case.
AB  - Phakomatous choristoma is a rare congenital hamartoma of lens tissue. It presents
      in newborns or young infants as a subcutaneous mass in the medial lower eyelid.
      We present a case of phakomatous choristoma recently identified among old
      consultation files at Children's Hospital in Boston. Our case illustrates unique
      histological features of this entity which has to be included in differential
      diagnosis of skin lesions of the inferonasal eyelid.

PMID- 15239683
TI  - Metastatic papillary carcinoma of the thyroid.
AB  - BACKGROUND: Cutaneous metastases from thyroid carcinomas, although uncommon, have
      been previously reported and are usually found in association with evidence of
      disseminated disease. METHODS: We report a 75-year-old male who presented with a
      4-cm reddish violaceous nodule on the left temple and a clinical history
      significant for papillary carcinoma of the thyroid. RESULTS: Microscopic
      examination of a 4-mm punch biopsy revealed a poorly circumscribed neoplasm with
      focal epidermal connection and multiple cystic cavities and papillary
      projections. CONCLUSIONS: This case report describes a solitary cutaneous lesion
      as the first evidence of disseminated neoplastic disease in a patient with no
      other clinical evidence of concurrent metastases. The histology of the lesion was
      unusual in that it mimicked a primary cutaneous neoplasm.

PMID- 15239685
TI  - Foreign bodies in cutaneous sarcoidosis.

PMID- 15239684
TI  - Early histopathologic changes in purple glove syndrome.
AB  - An 86-year-old African-American man presented with tonic-clonic seizures.
      Intravenous phenytoin was urgently administered into the dorsum of the right
      hand. The patient developed a raised purple area of discoloration around the
      intravenous insertion site within 2 h and edema and vesiculobullous lesions of
      the distal forearm, hands, and fingers within 8 h. Microscopic sections from a
      biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild
      superficial and deep perivascular lymphoid infiltrate, associated with numerous
      thrombi of small vessels throughout the dermis. The findings were judged to be
      consistent with soft-tissue injury associated with intravenous administration of
      phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for
      its distinctive purple discoloration and swelling of the hands in the
      distribution of a glove, is an uncommon complication of intravenous phenytoin
      administration through small dorsal veins of the hands. It is comprised by pain,
      discoloration, and edema in the vicinity of intravenous infusion of phenytoin
      through dorsal veins of the hand. The histopathologic features of fully developed
      lesions have been reported; however, early-stage findings have not been
      previously described, and the histogenesis of this lesion is controversial. The
      presence of thrombi in this early-stage lesion suggests that thrombosis plays a
      role in the initial pathogenesis of this condition.

PMID- 15239689
TI  - Colonization of the chicken reproductive tract and egg contamination by
      Salmonella.

PMID- 15239690
TI  - Physiological characterization of Mycobacterium sp. strain 1B isolated from a
      bacterial culture able to degrade high-molecular-weight polycyclic aromatic
      hydrocarbons.
AB  - AIM: The aim of this study was to further characterize a bacterial culture (VUN
      10,010) capable of benzo[a]pyrene cometabolism. METHODS AND RESULTS: The
      bacterial culture, previously characterized as a pure culture of Stenotrophomonas
      maltophilia (VUN 10,010), was found to also contain another bacterial species
      (Mycobacterium sp. strain 1B), capable of degrading a similar range of PAH
      substrates. Analysis of its 16S rRNA gene sequence and growth characteristics
      revealed the strain to be a fast-growing Mycobacterium sp., closely related to
      other previously isolated PAH and xenobiotic-degrading mycobacterial strains.
      Comparison of the PAH-degrading characteristics of Mycobacterium sp. strain 1B
      with those of S. maltophilia indicated some similarities (ability to degrade
      phenanthrene and pyrene), but some differences were also noted (S. maltophilia
      able to degrade fluorene, but not fluoranthene, whereas Mycobacterium sp. strain
      1B can degrade fluoranthene, but not fluorene). Unlike the S. maltophilia
      culture, there was no evidence of benzo[a]pyrene degradation by Mycobacterium sp.
      strain 1B, even in the presence of other PAHs (ie pyrene) as co-metabolic
      substrates. Growth of Mycobacterium sp. strain 1B on other organic carbon sources
      was also limited compared with the S. maltophilia culture. CONCLUSIONS: This
      study isolated a Mycobacterium strain from a bacterial culture capable of
      benzo[a]pyrene cometabolism. The Mycobacterium strain displays different PAH
      degrading characteristics to those described previously for the PAH-degrading
      bacterial culture. It is unclear what role the two bacterial strains play in
      benzo[a]pyrene cometabolism, as the Mycobacterium strain does not appear to have
      endogenous benzo[a]pyrene degrading ability. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study describes the isolation and characterization of a novel PAH
      degrading Mycobacterium strain from a PAH-degrading culture. Further studies
      utilizing this strain alone, and in combination with other members of the
      consortium, will provide insight into the diverse roles different bacteria may
      play in PAH degradation in mixed cultures and in the environment.

PMID- 15239691
TI  - Degradation of trehalose by rhizobia and characteristics of a trehalose-degrading
      enzyme isolated from Rhizobium species NGR234.
AB  - AIMS: This study was designed to examine the breakdown of trehalose by rhizobia
      and to characterize the trehalose-degrading enzyme isolated from Rhizobium sp.
      NGR234. METHODS AND RESULTS: Rhizobium sp. NGR234, Rhizobium fredii USDA257, R.
      phaseoli RCR3622, R. tropici CIAT899 and R. etli CE3 showed good growth in the
      presence of carbohydrate. Validamycin A did not prevent the growth of NGR234 on
      trehalose. The expression of a trehalose-degrading enzyme by NGR234 was
      intracellular and inducible by trehalose. The isolated enzyme digested other
      disaccharides, p-nitrophenyl-alpha-d-glucopyranoside and the substrate. The
      enzyme showed optimum activities at pH 7.0 and 30 degrees C. Its pI was 4.75 and
      the V(max) of the enzyme occurred at 35.7 micromol s(-1) mg(-1) protein with the
      K(m) of 23 mmol when trehalose was hydrolysed. CONCLUSIONS: An enzyme capable of
      breaking down trehalose was produced. Some of the properties of the trehalose
      degrading enzyme are similar to those isolated from other organisms but, this
      enzyme was validamycin resistant. These rhizobia like other trehalose-degrading
      microbes use trehalose by enzymatic catabolic action. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Trehalose which accumulates during legume-rhizobia symbiosis is toxic
      to plants. Detoxification by trehalose-degrading enzymes is important for the
      progress of symbiosis.

PMID- 15239692
TI  - Impact of cleaning and disinfection agents on biofilm structure and on microbial
      transfer to a solid model food.
AB  - AIM: To determine how single cells and microcolonies transfer to food from open
      surfaces in the meat industry. METHODS AND RESULTS: Biofilms of four bacterial
      strains isolated from food processing surfaces were established on stainless
      steel substrates conditioned with meat exudate in the presence or absence of
      CaCl(2). Image analysis of the biofilms showed that the addition of calcium
      resulted in an increase of the number and size of microcolonies with two strains:
      Staphylococcus sciuri and Pseudomonas fluorescens. Image analysis of the biofilms
      of those two strains grown in the presence of calcium was performed before and
      after contacts with tryptone soya agar as a solid model food. For the biofilms
      treated or not with a chlorinated alkaline agent, where a decrease in surface
      coverage occurred, it was accompanied by a decrease in the percentage of the
      coverage accounted for by microcolonies (P(m)). Attachment strength was greater
      for P. fluorescens than for S. sciuri. When the P. fluorescens biofilms were
      treated with a solution containing glutaraldehyde, the contacts did not modify
      their structure. By contrast, their treatment with chlorinated alkaline resulted,
      after contacts, in the smallest coverage and P(m). With S. sciuri, a decrease in
      coverage after contacts always occurred and was the greatest for the untreated
      biofilms. CONCLUSIONS: After contacts between biofilms and a solid model food,
      microcolonies were preferentially detached compared with single cells. A
      chlorinated alkaline product either decreased biofilm attachment strength (P.
      fluorescens) or unexpectedly increased it (S. sciuri), whereas a glutaraldehyde
      based disinfectant increased both attachment strength and microcolony cohesion.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The contaminating potential of a surface
      depends not only on the level of contamination but also on the nature, structure
      and history of the contamination.

PMID- 15239693
TI  - Diversity and dynamics of communities of coagulase-negative staphylococci in
      traditional fermented sausages.
AB  - AIMS: Evaluation of composition and evolution of the coagulase-negative
      staphylococci (CNS) communities in two traditionally fermented sausages
      (salsiccia and soppressata lucana) produced in Basilicata, southern Italy.
      METHODS AND RESULTS: A culture-dependent approach based on isolation on selective
      media and identification with phenotypic and molecular methods was used.
      Phenotypic data of 471 strains were analysed by multivariate statistical methods
      by using 28 strains from culture collections and 48 strains identified by
      molecular methods (such as 16S rDNA sequencing, species-specific PCR assays,
      intergenic spacer region-PCR and PCR-denaturing gradient gel electrophoresis) as
      a reference. The CNS microflora of the sausages was found to be dominated by
      different biotypes of Staphylococcus xylosus (51.2%), followed by S.
      pulvereri/vitulus, S. equorum and S. saprophyticus (13.4, 10.2 and 10%,
      respectively). Other species (S. succinus, S. pasteuri, S. epidermidis, S.
      warneri and Macrococcus caseolyticus) were also present at lower levels.
      Identification of 25% of the isolates was impossible. CONCLUSIONS: The
      composition of CNS communities varied significantly with sausage type, plant and
      ripening time and clear differences were found among communities of salsiccia and
      soppressata at the end of ripening. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Phenotypic characterization, supported by molecular and statistical analyses, can
      be considered a useful approach for typing a large number of isolates and for
      monitoring the evolution of staphylococcal communities during sausage
      fermentation but does not always provide a satisfactory identification of the
      isolates.

PMID- 15239694
TI  - Detection of free and plankton-associated Helicobacter pylori in seawater.
AB  - AIMS: To detect both free and plankton-associated Helicobacter pylori in seawater
      samples collected on the Italian coast of the Adriatic Sea using a nested-PCR.
      METHODS AND RESULTS: Dissolved oxygen, pH, salinity and chlorophyll 'a' were the
      parameters recorded together with the characterization of zooplanktonic
      organisms. Plankton-associated H. pylori DNA was searched for in water samples
      filtered through 200 and 64 microm nylon nets whereas free bacteria were retained
      with the subsequent filtration through 0.22 microm pore-size membranes. Nested
      PCR using primers for the glmM (ureC) gene was performed to reveal the presence
      of H. pylori. The DNA sequencing of amplified products confirmed the specificity
      of the assay. The sensitivity of the nested-PCR assay for H. pylori detection was
      62 CFU per 100 ml in spiked water samples. Helicobacter pylori either free or
      bound to planktonic organisms was found in seven of 12 monthly samples. In
      particular, free bacteria were detected during the summer sampling and in
      November, December and March associated to planktonic cells. CONCLUSIONS: The
      presence of free and plankton-associated H. pylori in seawater suggests that it
      can be a significant reservoir and a potential route of transmission for the
      microorganism. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study seems to provide a
      promising background to define new and effective strategies for surveillance of
      this human pathogen.

PMID- 15239695
TI  - Comparison of application methods to prolong the survival of potential biocontrol
      bacteria on stored sugar-beet seed.
AB  - AIMS: To develop bacterial inoculation treatments on sugar-beet seed that will
      maintain a commercially acceptable degree of viability for a minimum of 4 months
      storage at ambient temperature. METHODS AND RESULTS: Single rifampicin-resistant
      (Rif(+)) strains of both Gram-positive and negative bacterial isolates (mostly
      pseudomonads) were applied in turn to sugar-beet seed in a comparative study by
      seed soaking, encapsulation in alginate, pelleting using an inoculated peat
      carrier or seed priming. The treated seed was assessed for bacterial survival
      over a time course by plating out homogenized samples onto a selective medium.
      Priming inoculation offered a significant improvement over all the other
      application strategies tested. After pelleting with fungicides and drying at 40
      degrees C, Pseudomonas marginalis/putida P1W1 maintained populations of >6.6
      log(10) CFU g(-1) seed during 4 months storage at 15 degrees C. Subsequent
      experiments verified a stabilized population under these storage conditions with
      commercial pellets at <7% moisture content. CONCLUSION: An inoculation method was
      established which allowed the survival on seed of a Gram-negative bacterium at
      ambient temperature with little loss in viability. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This has promising implications for the delivery of beneficial bacteria,
      especially Gram-negative strains, on sugar beet.

PMID- 15239696
TI  - Development of a high throughput screening method to test flavour-forming
      capabilities of anaerobic micro-organisms.
AB  - AIM: Development of a fast, automated and reliable screening method for screening
      of large collections of bacterial strains with minimal handling time. METHODS AND
      RESULTS: The method is based on the injection of a small headspace sample (100
      microl) from culture vials (2 ml) in 96-well format directly into the mass
      spectrometry (MS). A special sample tray has been developed for liquid media, and
      anaerobically grown cultures. In principle, all volatile components can be
      measured, but a representative mass fragment has to be obtained in the MS.
      Representative masses for 3-methylbutanal, 2-methylpropanal and benzaldehyde are
      58, 72 and 105, respectively. In 1 day over 1500 samples could be analysed and
      the coefficient of variation for the response was <5%. CONCLUSION: Screening of
      72 strains belonging to the genus Lactococcus in quadruple on the production of
      the key-flavour compound 3-methylbutanal illustrated the effectiveness of the
      method. Furthermore, knowledge of the biochemistry and physiology of 3
      methylbutanal formation was used to optimize the composition of the growth medium
      to enhance 3-methylbutanal production, and thereby improve the screening.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A commonly used method to control flavour
      formation in fermented food products is the selection of bacterial strains, which
      are able to produce the desired flavour compounds. As large collections of
      strains are available for such screenings, studying biodiversity of micro
      organisms on the level of metabolic routes is strongly facilitated by highly
      automated high throughput screening methods for measuring enzyme activities or
      production of metabolites. Therefore, this method will be a useful tool for
      selecting flavour-producing strains and for enhancing starter culture
      development.

PMID- 15239697
TI  - Development of polythene films for food packaging activated with an antilisterial
      bacteriocin from Lactobacillus curvatus 32Y.
AB  - AIMS: The aims of this work were to (i) use a bacteriocin produced by
      Lactobacillus curvatus 32Y active against Listeria monocytogenes to activate
      polythene films by different methods, (ii) implement a large-scale process for
      antilisterial polythene films production and (iii) verify the efficacy of the
      developed films in inhibiting the growth of L. monocytogenes during the storage
      of meat products. METHODS AND RESULTS: The film was made active by using the
      antilisterial bacteriocin 32Y by Lact. curvatus with three different procedures:
      soaking, spraying and coating. The antimicrobial activity of the activated films
      was tested in plate assays against the indicator strain L. monocytogenes V7. All
      the used procedures yielded active polythene films although the quality of the
      inhibition was different. The coating was therefore employed to develop active
      polythene films in an industrial plant. The antimicrobial activity of the
      industrially produced films was tested in experiments of food packaging involving
      pork steak and ground beef contaminated by L. monocytogenes V7 at roughly 10(3)
      CFU cm(-2) and gram respectively. The results of the challenge tests showed the
      highest antimicrobial activity after 24 h at 4 degrees C, with a decrease of
      about 1 log of the L. monocytogenes population. CONCLUSIONS: Antimicrobial
      packaging can play an important role in reducing the risk of pathogen
      development, as well as extending the shelf life of foods. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Studies of new food-grade bacteriocins as preservatives and
      development of suitable systems of bacteriocin treatment of plastic films for
      food packaging are important issues in applied microbiology and biotechnology,
      both for implementing and improving effective hurdle technologies for a better
      preservation of food products.

PMID- 15239698
TI  - Relationship between thermotolerance and hydrophobin-like proteins in aerial
      conidia of Beauveria bassiana and Paecilomyces fumosoroseus as fungal biocontrol
      agents.
AB  - AIMS: This study was to illustrate the relationship between the thermotolerance
      and the contents of hydrophobin-like or formic-acid-extractable (FAE) proteins in
      aerial conidia of Beauveria bassiana and Paecilomyces fumosoroseus produced on
      rice-based substrate. METHODS AND RESULTS: Survival indices of 11 isolates were
      separately assessed as a ratio of the viability of conidia after 3-150 min
      thermal stress at 48 degrees C over that of unstressed conidia and fitted well to
      a survival model (r(2) >/= 0.97). For a given isolate, the fitted model generated
      an LT(50), the time for 50% viability loss under the stress. The LT(50)s of six
      B. bassiana isolates (10.1-61.9 min) and five P. fumosoroseus isolates (2.8-6.2
      min) were correlated (r(2) = 0.81) with FAE protein contents (6.9-23.4 microg mg(
      1)). The survival indices of a fixed B. bassiana isolate after 45-min thermal
      stress at 48 degrees C were also correlated to the FAE protein contents from
      conidia produced on glucose-, sucrose-, or starch-based substrate (0.79 </= r(2)
      </= 0.86). Three bands of 12.0, 15.0 and 17.5 kDa were recognized from SDS-PAGE
      profiles of protein extracts from different isolates or from the fixed isolate
      grown on the three carbon sources, but the 12 kDa was less likely related to the
      thermotolerance. CONCLUSIONS: Approximately 80% of variability in conidial
      thermotolerance was attributed to either 15.0- or 17.5-kDa FAE protein or both.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The relationship between conidial
      thermotolerance and FAE protein contents implicates a new way to search for
      fungal biocontrol agents with more thermotolerance and environmental persistence.

PMID- 15239699
TI  - pH control of the production of recombinant glucose oxidase in Aspergillus
      nidulans.
AB  - AIMS: Recombinant Aspergillus nidulans sVAL040, capable of synthesizing and
      secreting glucose oxidase derived from Aspergillus niger was used to study the
      influence of pH and carbon source on enzyme production. METHODS AND RESULTS:
      Glucose oxidase gene (goxC) was expressed under transcriptional regulation by
      using the promoter of A. nidulans xlnB gene (encoding an acidic xylanase). A
      maximum specific glucose oxidase activity of approx. 10 U mg(-1) protein and a
      maximum volumetric productivity of 29.9 U l(-1) h(-1) were obtained at pH 5.5,
      after 80 h of growth by using xylose as inducer. Enzyme volumetric productivity
      increased when xylans were used instead of xylose; however, specific glucose
      oxidase activity did not differ significantly. CONCLUSIONS: Specific GOX activity
      obtained at pH 5.5 are two to three times more than those previously described
      for goxC multicopy transformants of A. nidulans. Xylans were a more powerful
      inducer than xylose although fungal growth was lower when the polymers were used.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The obtained results by using xlnB promoter
      in A. nidulans could be useful in improving heterologous enzyme production by
      using genetic- and process-engineering strategies.

PMID- 15239700
TI  - Improvement of bioinsecticides production through mutagenesis of Bacillus
      thuringiensis by u.v. and nitrous acid affecting metabolic pathways and/or delta
      endotoxin synthesis.
AB  - AIMS: The present work aimed to obtain bioinsecticide over-producing mutants
      through classical mutagenesis of vegetative cells of Bacillus thuringiensis (Bt)
      by using u.v. and nitrous acid, and to evidence the involvement of cell
      metabolism in delta-endotoxin synthesis. METHODS AND RESULTS: Vegetative cells of
      Bt were treated by nitrous acid (0.17 mg ml(-1)) or exposed to u.v. rays (emitted
      at a wave length of 240 nm). The isolated survivors were screened on the basis of
      the production of delta-endotoxins and biomass in glucose and/or in gruel-based
      media at two aeration conditions. Bioinsecticide over-producing mutants were
      obtained with high frequencies because random mutations were shown to affect cell
      metabolism at different pathways related to the regulation of delta-endotoxin
      synthesis. CONCLUSIONS: Classical mutagenesis of Bt cells lead to the isolation
      of a large variety of delta-endotoxin over-producing mutants that could be
      classified into six groups based on the location of the mutations, particularly
      in metabolism pathways and delta-endotoxin synthesis. SIGNIFICANCE AND IMPACT OF
      THE STUDY: High frequencies of delta-endotoxin over-producing mutants of Bt could
      be obtained through classical mutagenesis of vegetative cells. This should
      contribute to a significant reduction of production and utilization costs of Bt
      bioinsecticides.

PMID- 15239701
TI  - Determination of toxicity of Campylobacter jejuni isolated from humans and from
      poultry carcasses acquired at various stages of production.
AB  - AIM: The research focused on the determination of the toxicity variation
      associated with Campylobacter jejuni isolated from humans and chickens. METHODS
      AND RESULTS: Campylobacter jejuni isolates were obtained from chicken carcasses
      and from humans exhibiting symptoms of campylobacteriosis. Using HeLa cells as
      the in vitro model, toxicity was determined for each isolate. The mean toxicity
      level of the chicken isolates was significantly lower than that of the human
      isolates (P < 0.001). There was a wide range of toxicity in C. jejuni isolated
      from chickens and the percentage of isolates exhibiting low toxicity remaining
      relatively constant. All C. jejuni isolates from humans possessed either medium
      or high levels of toxicity. CONCLUSIONS: All wildtype C. jejuni isolates obtained
      from poultry carcasses may not be equally important as a human foodborne
      pathogen. SIGNIFICANCE AND IMPACT OF STUDY: Campylobacter jejuni remains a
      primary foodborne pathogen and increased efforts are needed to determine the
      impact of wildtype isolates in causing human illness. The present research
      indicates that all isolates may not be equally important in regards to disease
      potential. The information found should be included in efforts to develop C.
      jejuni detection, control and infection modelling.

PMID- 15239702
TI  - Distribution of potentially pathogenic bacteria as free living and plankton
      associated in a marine coastal zone.
AB  - AIMS: To determine the abundance of faecal and nonfaecal bacteria related to
      human and animal health, as free living or associated with small (>64 microm) and
      large (>200 microm) plankton, samples were collected monthly from the coastal
      zone at Messina (Italy). METHODS AND RESULTS: Different enrichment and selective
      cultural methods were used to determine the abundance of bacteria in sea water
      and plankton. The bacteria were more frequently isolated from water and large
      plankton than from small plankton. Vibrio and Aeromonas spp. showed different
      distribution patterns in water and plankton. Faecal indicators were always
      present in water and the large size class plankton samples. Enterococci
      associated with large plankton were more abundant than E. coli in the winter.
      Vibrio species distributions were different in water and plankton samples. Among
      arcobacters only A. butzleri was isolated from water and plankton samples.
      Campylobacter spp. was always absent in small plankton and more frequent in large
      plankton than in water. CONCLUSIONS: The colonization of zooplankton by
      potentially pathogenic bacteria is a widespread phenomenon. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The presence of potentially pathogenic bacteria in sea water
      and associated with plankton can have ecological and epidemiological
      implications.

PMID- 15239703
TI  - The prevalence and concentration of Escherichia coli O157 in faeces of cattle
      from different production systems at slaughter.
AB  - AIMS: To determine the prevalence and concentration of Escherichia coli O157 shed
      in faeces at slaughter, by beef cattle from different production systems. METHODS
      AND RESULTS: Faecal samples were collected from grass-fed (pasture) and lot-fed
      (feedlot) cattle at slaughter and tested for the presence of E. coli O157 using
      automated immunomagnetic separation (AIMS). Escherichia coli O157 was enumerated
      in positive samples using the most probable number (MPN) technique and AIMS and
      total E. coli were enumerated using Petrifilm. A total of 310 faecal samples were
      tested (155 from each group). The geometric mean count of total E. coli was 5 x
      10(5) and 2.5 x 10(5) CFU g(-1) for lot- and grass-fed cattle, respectively.
      Escherichia coli O157 was isolated from 13% of faeces with no significant
      difference between grass-fed (10%) and lot-fed cattle (15%). The numbers of E.
      coli O157 in cattle faeces varied from undetectable (<3 MPN g(-1)) to 1.1 x 10(5)
      MPN g(-1). Twenty-six (67%) of 39 O157 positive faeces had <10 MPN g(-1) and
      three (8%) had counts between 10(3)-10(5) MPN g(-1). There was no significant
      difference between concentrations of E. coli O157 in the faeces of grass-fed or
      lot-fed cattle. CONCLUSION: The prevalence and numbers of E. coli O157 in the
      faeces of cattle at slaughter were not affected by the production systems
      evaluated in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on the
      prevalence and numbers of E. coli O157 can be used for formulating intervention
      strategies and in quantitative risk assessments.

PMID- 15239704
TI  - Effects of antimicrobial treatment on fiberglass-acrylic filters.
AB  - AIMS: The aims of the present study were to: (i) analyse a group of antimicrobial
      agents and to select the most active against test microbial strains; (ii) test
      the effect of the antimicrobial treatment on air filters in order to reduce
      microbial colonization. METHODS AND RESULTS: Different kinds of antimicrobial
      agents were analysed to assess their compatibility with the production process of
      air filter media. The minimal inhibitory concentration for each antimicrobial
      agent was determined against a defined list of microbial strains, and an
      antimicrobial activity assay of filter prototypes was developed to determine the
      most active agent among the compatible antimicrobials. Then, the most active was
      chosen and added directly to the filter during the production process. The
      microbial colonization of treated and untreated filter media was assessed at
      different working times for different incubation times by stereomicroscope and
      scanning electron microscope analysis. Some of the antimicrobial agents analysed
      were more active against microbial test strains and compatible with the
      production process of the filter media. Filter sections analysis of treated
      filter media showed a significantly lower microbial colonization than those
      untreated, a reduction of species both in density and varieties and of the
      presence of bacteria and fungal hyphae with reproductive structures. CONCLUSIONS:
      This study demonstrated the ability of antimicrobial treatments to inhibit the
      growth of micro-organisms in filter media and subsequently to increase indoor air
      quality (IAQ), highlighting the value of adding antimicrobials to filter media.
      SIGNIFICANCE AND IMPACT OF THE STUDY: To make a contribution to solving the
      problem of microbial contamination of air filters, by demonstrating the efficacy
      of incorporating antimicrobial agents in the filter media to improve IAQ and
      health.

PMID- 15239706
TI  - Simultaneous detection of Carnobacterium and Leuconostoc in meat products by
      multiplex PCR.
AB  - AIMS: To develop a multiplex PCR approach for simultaneous detection of
      Leuconostoc and Carnobacterium and its validation in meat products. METHODS AND
      RESULTS: Two multiplex PCR assays were developed using newly designed 16S rDNA
      directed primers adapted to the current taxonomic situation of genera Leuconostoc
      and Carnobacterium that allow: (i) simultaneous detection of both genera, and
      members of the nonmotile species of genus Carnobacterium and (ii) identification
      in a single assay of the nonmotile species C. divergens, C. maltaromicum and C.
      gallinarum. Sensitivity values of 10(3) and 10(4) CFU g(-1) were determined for
      multiplex PCR detection of Carnobacterium and Leuconostoc, respectively,
      following artificially inoculated meat trials. In addition, both multiplex PCR
      assays were validated in 14 naturally contaminated samples covering nine types of
      meat products. Results obtained by colony identification were confirmed by PCR
      detection. CONCLUSIONS: The methods described in this study provide a rapid and
      reliable tool for PCR detection of Carnobacterium and Leuconostoc, in meat
      products, and for colony identification. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This multiplex PCR approach will help in the analysis of the spoilage microbiota
      of refrigerated vacuum-packaged meat product in order to determine the
      appropriate preservation method.

PMID- 15239705
TI  - Phylogenetic analysis of protozoa in the rumen contents of cow based on the 18S
      rDNA sequences.
AB  - AIMS: To examine the diversity of protozoa in the rumen contents of cow. METHODS
      AND RESULTS: Protozoa that inhabit the rumen were detected by PCR using protozoan
      specific primers. Libraries of protozoan rDNA sequences were constructed from
      rumen fluid, solid tissues and epithelium. Twenty-three clones isolated from
      rumen fluid fell into two genera identified as Entodinium (69.6% of clones) and
      Epidinium (31.4% of clones). Of the clones isolated from rumen fluid, a moderate
      number were unidentifiable (30.4%). CONCLUSIONS: The predominant protozoan genus
      identified in the whole rumen belonged to the Entodinium group (81.1%). Protozoa
      were not detected in the rumen epithelium. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These findings suggest that rumen fluid and solid tissues contain different
      protozoan populations that may play specific roles in rumen function.
      Quantitative PCR techniques and a more specific set of phylogenetic probes that
      distinguish between protozoan species are needed to determine the significance of
      newly identified groups and to determine the distribution of identified protozoan
      clusters in rumen microbial communities.

PMID- 15239707
TI  - Efficiency of Calamintha officinalis essential oil as preservative in two topical
      product types.
AB  - AIMS: To verify the efficiency of Calamintha officinalis essential oil as natural
      preservative in two current formulations. METHODS AND RESULTS: The 1.0 and 2.0%
      (v/v) C. officinalis essential oil was assayed for its preservative activity in
      two product types (cream and shampoo). The microbial challenge test was performed
      following the standards proposed by the European Pharmacopoeia Commission (E.P.)
      concerning topical preparations using standard micro-organisms and in addition
      wild strains, either in single or mixed cultures were used. The results clearly
      demonstrated that the C. officinalis essential oil at 2.0% concentration reduced
      the microbial inoculum satisfying the criterion A of the E.P. in the cream
      formulation and the criterion B in the shampoo formulation. Standard and wild
      strains showed a behaviour similar, both in cream and in shampoo formulation,
      with no significant difference (gerarchic variance, P > 0.05). CONCLUSION: C.
      officinalis essential oil confirmed its preservative properties but at higher
      concentration than that shown in previous studies on cetomacrogol cream.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The nature of the formulation in which an
      essential oil is incorporated as preservative could have considerable effect on
      its efficacy.

PMID- 15239708
TI  - An effective iodide formulation for killing Bacillus and Geobacillus spores over
      a wide temperature range.
AB  - AIMS: To develop a sporicidal reagent which shows potent activity against
      bacterial spores not only at ambient temperatures but also at low temperatures.
      METHODS AND RESULTS: Suspension tests on spores of Bacillus and Geobacillus were
      conducted with the reagent based on a previously reported agent (N. Kida, Y.
      Mochizuki and F. Taguchi, Microbiology and Immunology 2003; 47: 279-283). The
      modified reagent (tentatively designated as the KMT reagent) was composed of 50
      mmol l(-1) EDTA-2Na, 50 mmol l(-1) ferric chloride hexahydrate (FeCl(3).6H(2)O),
      50 mmol l(-1) potassium iodide (KI) and 50% ethanol in 0.85% NaCl solution at pH
      0.3. The KMT reagent showed significant sporicidal activity against three species
      of Bacillus and Geobacillus spores over a wide range of temperature. The KMT
      reagent had many practical advantages, i.e. activity was much less affected by
      organic substances than was sodium hypochlorite, it did not generate any harmful
      gas and it was stable for a long period at ambient temperatures. The mechanism(s)
      of sporicidal activity of the KMT reagent was considered to be based on active
      iodine species penetrating the spores with enhanced permeability of the spore
      cortex by a synergistic effect of acid, ethanol and generated active oxygen.
      CONCLUSIONS: The data suggest that the KMT reagent shows potent sporicidal
      activity over a wide range temperatures and possesses many advantages for
      practical applications. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      indicate development of a highly applicable sporicidal reagent against Bacillus
      and Geobacillus spores.

PMID- 15239710
TI  - Genetic fingerprinting of Flavobacterium columnare isolates from cultured fish.
AB  - AIMS: To evaluate the intraspecific diversity of the fish pathogen Flavobacterium
      columnare. METHODS AND RESULTS: Genetic variability among Fl. columnare isolates
      was characterized using restriction fragment length polymorphism analysis of the
      16S rDNA gene, intergenic spacer region (ISR) sequencing, and amplified fragment
      length polymorphism (AFLP) fingerprinting. Thirty Fl. columnare cultures isolated
      from different fish species and geographical origins as well as reference strains
      were included in the study. Fifteen isolates belonged to genomovar I while eleven
      were ascribed to genomovar II. Analysis of the ISR sequence confirmed the genetic
      differences between both genomovars but revealed a higher diversity among
      genomovar I isolates. The maximum resolution was provided by AFLP fingerprinting,
      as up to 22 AFLP profiles could be defined within the species. CONCLUSIONS: We
      confirmed the division of Fl. columnare isolates from cultured fish into
      different genogroups. We showed that both genomovars I and II are present in
      channel catfish from the US. We described a unique genetic group represented by
      four Fl. columnare isolates from tilapia in Brazil which appears to be related to
      both genomovars. We were able to further subdivide the species by analysing the
      ISR. Finally, the use of AFLP allowed us to fingerprint the species at clone
      level without losing the higher genetic hierarchy of genomovar division.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This paper reports on an extensive
      assessment of the use of molecular tools for the study of the epidemiology of the
      fish pathogen Fl. columnare.

PMID- 15239711
TI  - Modelling the effect of temperature and water activity on growth of Aspergillus
      niger strains and applications for food spoilage moulds.
AB  - AIMS: To develop a model for the combined effect of water activity (a(w)) and
      temperature on growth of strains of Aspergillus niger, and comparison with data
      on food spoilage moulds in the literature. METHODS AND RESULTS: An extended
      combined model describing the growth of two strains of A. niger, as a function of
      temperature (25-30 degrees C) and a(w) (0.90-0.99) was developed. The growth rate
      (micro) was expressed as the increase in colony radial growth per unit of time.
      This extends the previous square root model showing the relationship between
      temperature and bacterial growth rate developed by Ratkowsky et al. (1983) and
      the parabolic relationship between the logarithm of the growth rate and a(w)
      developed by Gibson et al. (1994). A good correlation between the experimental
      data and the model predictions was obtained, with regression coefficients (r(2))
      > 0.99. In addition, the use of this model allowed predictions of the cardinal
      a(w) levels: a(w(min)), and a(w(opt)). The estimation of the minimum a(w) levels
      (a(w(min))) was in accordance with data in the literature for similar and a range
      of other Aspergillus and related species, regardless of the solutes used for a(w)
      modification. The estimation of the optimal a(w) (a(w(opt))) and the optimal
      growth rate (micro(opt)) were in good agreement with the experimental results and
      data from the literature. CONCLUSIONS: This approach enables accurate prediction
      of the combined effects of environmental factors on growth of spoilage fungi for
      rapid prediction of cardinal limits using surface response curves. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This approach is a rapid method for predicting optimal
      and marginal conditions for growth of a wide range of spoilage micro-organisms in
      relation to interacting environmental conditions and will have applications for
      improving shelf-life of intermediate moisture foods.

PMID- 15239709
TI  - Chronic shedding of Campylobacter species in beef cattle.
AB  - AIMS: To determine the prevalence of chronic shedding of Campylobacter species by
      beef cattle, a longitudinal study of shedding patterns was conducted in a cohort
      of 60 beef steers over a 4-month period. METHODS AND RESULTS: Steers were
      maintained in a simulated feedlot setting but individually in pens to minimize
      transmission among animals. At each collection time, campylobacters in faeces
      were detected using conventional PCR. In addition, quantities of Campylobacter
      jejuni and C. lanienae in faeces were measured using real-time quantitative (RTQ)
      PCR. All of the steers tested shed Campylobacter species during the course of the
      study, and overall, 90% of the 299 samples tested were positive for Campylobacter
      DNA. The majority of the animals (86%) shed campylobacters at >/=4 sample times.
      The most prevalent taxon detected in bovine faeces was C. lanienae (56% of
      samples) followed by C. jejuni (13%), C. hyointestinalis (8%), and C. fetus (2%).
      No C. coli was detected, and 13% of the faecal samples contained two or more of
      the above species. Seven (12%) and 34 (57%) animals shed C. jejuni and C.
      lanienae at >/=3 sample times, respectively. For both C. lanienae and C. jejuni,
      a substantial number of cells were detected in faeces using RTQ-PCR; 27% of the
      samples positive for C. jejuni contained populations >10(4) cells g(-1) (maximum
      of 5 x 10(5) cells g(-1)), and 44% of samples positive for C. lanienae possessed
      populations >10(6) cells g(-1) (maximum of 4 x 10(8) cells g(-1)). A significant
      correlation was observed between shedding of C. lanienae and the severity of
      liver abscesses. In 27% of the samples, an amplicon was obtained for genus
      specific but not for the species-specific primers. Sequencing of the partial 16S
      rRNA gene suggested the presence of at least two undescribed Campylobacter
      species but this has yet to be confirmed. CONCLUSIONS: A high percentage of
      feedlot cattle shed large quantities of Campylobacter species in their faeces
      over a protracted period of time (ca 112 days). SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first study of longitudinal shedding patterns of
      campylobacters in beef cattle using PCR-detection methods. In addition, this is
      the first use of RTQ-PCR to directly quantify C. jejuni or C. lanienae in faeces.
      The results of the study show that a large number of cattle (>85%) chronically
      shed campylobacters in feedlots.

PMID- 15239712
TI  - Water and temperature relations of growth and ochratoxin A production by
      Aspergillus carbonarius strains from grapes in Europe and Israel.
AB  - AIMS: This study investigated the in vitro effects of water activity (a(w); 0.85
      0.987) and temperature (10-40 degrees C) on growth and ochratoxin A (OTA)
      production by two strains of Aspergillus carbonarius isolated from wine grapes
      from three different European countries and Israel on a synthetic grape juice
      medium representative of mid-veraison (total of eight strains). METHODS AND
      RESULTS: The synthetic grape juice medium was modified with glycerol or glucose
      and experiments carried out for up to 56 days for growth and 25 days for OTA
      production. The lag phase prior to growth, growth rates and ochratoxin production
      were quantified. Statistical comparisons were made of all factors and multiple
      regression analysis used to obtain surface response curves of a(w) x temperature
      for the eight strains and optimum growth and OTA production by A. carbonarius.
      The lag phase increased from <1 day at 25-35 degrees C and 0.98 a(w) to >20 days
      at marginal temperatures and water availabilities. Generally, most A. carbonarius
      strains grew optimally at 30-35 degrees C, regardless of solute used to modify
      a(w), with no growth at <15 degrees C. The optimum a(w) for growth varied from
      0.93 to 0.987 depending on the strain, with the widest a(w) tolerance at 25-30
      degrees C. There was no direct relationship among growth, environmental factors
      and country of origin of individual strains. Optimum conditions for OTA
      production varied with strain. Some strains produced optimal OTA at 15-20 degrees
      C and 0.95-98 a(w). The maximum OTA produced after 10 days was about 0.6-0.7
      microg g(-1), with a mean production over all eight strains of 0.2 microg g(-1)
      at optimum environmental conditions. CONCLUSIONS: This work demonstrates that
      optimum conditions for OTA production are very different from those for growth.
      While growth rates differed significantly between strains, integration of the OTA
      production data suggests possible benefits for use of the information on a
      regional basis. SIGNIFICANCE AND IMPACT OF THE STUDY: Very little detailed
      information has previously been available on the ecology of A. carbonarius. This
      knowledge is critical in the development and prediction of the risk models of
      contamination of grapes and grape products by this species under fluctuating and
      interacting environmental parameters.

PMID- 15239713
TI  - Polyphasic study of the genetic diversity of lactobacilli associated with
      'Almagro' eggplants spontaneous fermentation, based on combined numerical
      analysis of randomly amplified polymorphic DNA and pulsed-field gel
      electrophoresis patterns.
AB  - AIMS: The goal of this study was to assess the genetic diversity of lactic acid
      bacteria (LAB) from the complex natural ecosystem present in the spontaneous
      fermentation of 'Almagro' eggplants by a polyphasic approach based on molecular
      techniques. METHODS AND RESULTS: Randomly amplified polymorphic DNA (RAPD) and
      pulsed-field gel electrophoresis (PFGE) were applied to 149 Lactobacillus
      isolates obtained from that fermentation process. Two random primers, OPL-05 and
      ArgDei-For, and two rare-cutting enzymes, SfiI and SmaI, chosen after preliminary
      testing on the basis of band intensity and distribution, were used. RAPD and PFGE
      generated electrophoretic patterns suitable for strain discrimination, but
      further discrimination was achieved when combined numerical analysis of the
      results from both methods and the results previously obtained by SDS-PAGE whole
      cell protein analysis, was carried out. The findings indicated a considerable
      degree of genomic diversity in the LAB microbiota studied and especially in the
      Lactobacillus plantarum isolates. In terms of species assignment, the polyphasic
      study allowed a definite and well-founded identification of 98.7% of the
      isolates. CONCLUSIONS: The combined numerical analysis of RAPD and PFGE patterns
      represented a useful tool to discriminate the diversity of the Lactobacillus
      strains responsible for the spontaneous fermentation of this pickle. The species
      identification and strain typing results from the polyphasic study were regarded
      as the most exact compromise yielding the fewest contradictions based on the
      available data. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined numerical analysis
      of RAPD-PCR and PFGE patterns has not yet been employed to study the genetic
      diversity of LAB from an ecosystem like that found in fermenting vegetables.

PMID- 15239716
TI  - British HIV Association (BHIVA)/British Association for Sexual Health and HIV
      (BASHH) guidelines on provision of adherence support to individuals receiving
      antiretroviral therapy (2003).
AB  - The widespread use of highly active antiretroviral therapy (HAART) has
      dramatically reduced HIV-associated morbidity and mortality where treatment has
      been made available. Very high levels of adherence to HAART are a prerequisite
      for a successful virological and immunological response. Low adherence increases
      the risk of treatment failure and disease progression. It is also likely to lead
      to further transmission of resistant viruses, and to have a negative impact on
      the cost effectiveness of HAART. Low adherence is difficult to predict, and this
      has two key implications for service provision. Firstly, HAART should not be
      withheld on the basis of assumptions about adherence. Secondly, support with
      adherence should be provided to all patients prescribed HAART. Our understanding
      of barriers to and enablers of high adherence, and the evidence base regarding
      effective interventions, is limited. Meta-analysis of randomized controlled
      trials available from the general literature suggests multiple interventions are
      required to maintain high adherence to chronic therapy. This document recommends
      a series of measures for adoption within HIV clinical care settings, based on
      evaluation of existing data. High adherence is a process, not a single event, and
      therefore adherence support must be integrated into clinical follow up. Every
      prescribing unit should have a written policy on provision of adherence support,
      and ensure that staff are appropriately trained to make delivery of such services
      possible.

PMID- 15239721
TI  - 10th International Conference on Emergency Medicine, 7-10 June 2004. Abstracts.

PMID- 15239717
TI  - PENTA guidelines for the use of antiretroviral therapy, 2004.
AB  - There have been few major advances in paediatric HIV management over the last 2
      years. Decisions about starting antiretroviral therapy can now be based on a
      recent large meta-analysis of the predictive value of CD4 and HIV RNA viral load
      (VL) in nearly 4000 untreated children, which is discussed in these updated
      guidelines. Risk estimates for progression to AIDS and death using surrogate
      markers can now be broken down by age, allowing more accurate discussion with
      families. In addition, there is increasing recognition of the problems of long
      term adherence, drug resistance and cumulative toxicity in adults and children.
      The controversy over whether to treat asymptomatic infants continues. For older
      children more data on the efficacy of ritonavir boosted protease inhibitor (PI)
      regimens suggests that these may be the PI option of first choice. There is still
      no adult or paediatric trial evidence on which to base decisions about whether to
      start with PI- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based
      regimens, but the PENPACT 1 trial, which is addressing this question, is ongoing.
      There are increasing moves to provide simpler antiretroviral therapy (ART)
      regimens, including once daily dosing, but these lag behind adult regimens
      because of the paucity of pharmacokinetic data. Resistance assays should now be
      performed in all HIV-infected infants exposed to ART in pregnancy. Therapeutic
      drug monitoring may be very important in children because of high between- and
      within-child variability in drug absorption and metabolism. A trial to evaluate
      this should start shortly in Europe (PENTA 14 trial). The value of resistance
      tests for choice of second-line and subsequent choices of ART regimens remain
      unproven (the PERA trial will report late in 2004), but resistance assays are
      increasingly being used. The issue of when to switch therapy also remains
      unanswered and is being addressed within the PENPACT 1 trial. Regular formal
      assessment of adherence is now the standard of care, and routine monitoring in
      the clinic for lipodystrophy syndrome (LDS) and other ART toxicities is
      increasingly important. These guidelines will be updated again in 2006.

PMID- 15239722
TI  - The dilemma of managing carbon monoxide poisoning.

PMID- 15239723
TI  - A pilot trial of BIS monitoring for procedural sedation in the emergency
      department.
AB  - OBJECTIVE: Procedural sedation is common in the ED. However, there is no
      objective physiologic parameter available to monitor a patient's conscious state.
      The Bispectral Index (BIS) monitor has been validated as an objective measure of
      depth of anaesthesia. We studied the BIS monitor for this role in procedural
      sedation. METHODS: A prospective, observational study with convenience sampling
      of adult patients in ED who underwent procedural sedation. Patients were treated
      according to standard practice and sedated as determined by the treating
      physician. Treating physicians were blinded to the BIS value. BIS values were
      recorded and compared to the Observer's Assessment of Alertness/Sedation Scale
      (OAAS). Upon recovery, patients were asked about recall of events while they were
      sedated. RESULTS: Twelve patients were enrolled and 110 paired readings from 11
      patients (7 male) were obtained. It was not possible to obtain readings from one
      patient. The mean age was 58 years (range 20-94). The Spearman correlation
      between BIS and OAAS was 0.027 (95% CI -0.582-0.617). For the three patients who
      received propofol, the correlation was 1.0. There were no episodes of explicit
      recall of events during the period of sedation. CONCLUSIONS: BIS monitoring is
      feasible in the ED. Our small study suggests that there is a poor correlation
      between BIS values and the OAAS scale. Larger studies are required to further
      explore this relationship. Further developments in brain monitoring technology
      are also needed before this form of monitoring becomes clinically useful for
      procedural sedation.

PMID- 15239724
TI  - Practicality of performing medical procedures in chemical protective ensembles.
AB  - OBJECTIVE: To determine whether certain life saving medical procedures can be
      successfully performed while wearing different levels of personal protective
      equipment (PPE), and whether these procedures can be performed in a clinically
      useful time frame. METHODS: We assessed the capability of eight medical personnel
      to perform airway maintenance and antidote administration procedures on manikins,
      in all four described levels of PPE. The levels are: Level A--a fully
      encapsulated chemically resistant suit; Level B--a chemically resistant suit,
      gloves and boots with a full-faced positive pressure supplied air respirator;
      Level C--a chemically resistant splash suit, boots and gloves with an air
      purifying positive or negative pressure respirator; Level D--a work uniform. Time
      in seconds to inflate the lungs of the manikin with bag-valve-mask, laryngeal
      mask airway (LMA) and endotracheal tube (ETT) were determined, as was the time to
      secure LMAs and ETTs with either tape or linen ties. Time to insert a cannula in
      a manikin was also determined. RESULTS: There was a significant difference in
      time taken to perform procedures in differing levels of personal protective
      equipment (F21,72 = 1.75, P = 0.04). Significant differences were found in: time
      to lung inflation using an endotracheal tube (A vs. C mean difference and
      standard error 75.6 +/- 23.9 s, P = 0.03; A vs. D mean difference and standard
      error 78.6 +/- 23.9 s, P = 0.03); time to insert a cannula (A vs. D mean
      difference and standard error 63.6 +/- 11.1 s, P < 0.001; C vs. D mean difference
      and standard error 40.0 +/- 11.1 s, P = 0.01). CONCLUSIONS: A significantly
      greater time to complete procedures was documented in Level A PPE (fully
      encapsulated suits) compared with Levels C and D. There was however, no
      significant difference in times between Level B and Level C. The common practice
      of equipping hospital and medical staff with only Level C protection should be re
      evaluated.

PMID- 15239725
TI  - The potential role of procalcitonin in the emergency department management of
      febrile young adults during a sustained meningococcal epidemic.
AB  - OBJECTIVE: To prospectively investigate the diagnostic characteristics of
      procalcitonin as an aid in the diagnosis of meningococcal disease in febrile
      young adults presenting to the Waikato Hospital emergency department during a
      sustained meningococcal epidemic. METHODS: The study population were emergency
      department patients aged 14-40 years presenting with either a temperature > or =
      38.0 degrees C without an obvious focus of infection, or symptoms consistent with
      meningococcal disease. All had procalcitonin levels, N. meningitidis PCR, blood
      +/- CSF cultures. RESULTS: One hundred and eighty-three patients presented with
      undifferentiated febrile illness over a 9 month study period. Nine were
      subsequently shown to have meningococcal disease. A positive procalcitonin (> or
      = 0.5 ng/mL) had a sensitivity of 100% (CI 66.4-100), specificity 89% (CI 83.1
      93.1), negative predictive value 100% (CI 97.6-100) and positive predictive value
      32% (CI 15.9-52.4) for meningococcal disease. CONCLUSIONS: The finding of a
      procalcitonin level > or = 0.5 ng/mL in young adults with undifferentiated fever
      indicates an increased chance that the presenting illness may be meningococcal
      disease. In New Zealand's continuing meningococcal epidemic empirical antibiotics
      should be strongly considered in those with elevated procalcitonin levels in the
      hope of reducing meningococcal disease deaths due to delays in antibiotic
      administration.

PMID- 15239726
TI  - Can serum mast cell tryptase help diagnose anaphylaxis?
AB  - OBJECTIVE: We aimed to determine the utility of serum mast cell tryptase to
      diagnose anaphylaxis. METHODS: As part of a venom immunotherapy trial, we
      performed 64 sting challenges. Blood samples were taken before the sting
      (baseline), and 15 min and 60 min after the sting. Tryptase was measured in
      baseline, 15 minute and 60 minute serum samples. Histamine was measured in
      baseline and 15 minute plasma samples. Eleven people had undisputed severe
      anaphylactic reactions; tryptase and histamine levels were assessed against this
      clinical gold standard diagnosis. RESULTS: Excluding mild reactions from the
      analysis, peak tryptase readings had sensitivity of 0.36 and specificity of 0.93
      using the recommended cut-off range (< 12.0 microg/L). Receiver-operator curve
      analysis found a cut-off of 9.0 microg/L would improve diagnostic performance
      (sensitivity 0.55, specificity 0.93). Serial tryptase measurement was
      significantly more discriminatory; an increase in tryptase of 2.0 microg/L or
      greater had a sensitivity of 0.73 and specificity of 0.98. The addition of
      histamine measurements, defining a positive result by either a rise in tryptase
      or a rise in histamine, appeared to further increase sensitivity (0.90).
      CONCLUSIONS: Clinicians should use caution when using serum tryptase to refute or
      support a diagnosis of anaphylaxis. Serial tryptase measurement increases
      sensitivity and specificity. Further studies using serial tryptase determinations
      in general emergency department practice, perhaps supplemented by histamine
      determinations, are warranted.

PMID- 15239727
TI  - Management of septic shock in childhood.
AB  - OBJECTIVE: The object of this review is to discuss the recognition and treatment
      of septic shock in children based on principles of resuscitation, antibiotic use
      and recent therapeutic advances. METHODS: A comprehensive literature search
      combining these METHODS: on-line searches of Ovid, PubMed, and Medline; hand
      searches of 25 international journals; a trawl of 26 textbooks; searches of
      reference lists of pertinent articles; and scans of abstracts of recent
      international meetings. Various national and international units were contacted
      with regard to current research therapeutic strategies, both published and
      unpublished. CONCLUSIONS: Septic shock remains a leading cause of morbidity and
      mortality in children. Early administration of empirical antibiotic therapy
      reduces mortality. The keystone of resuscitation is aggressive volume
      replacement. Adjunctive therapies to modulate the inflammatory response may
      further enhance outcome, but do not replace principles of resuscitation.

PMID- 15239728
TI  - How long does stridor at rest persist in croup after the administration of oral
      prednisolone?
AB  - OBJECTIVES: To determine the duration of stridor at rest (SAR) after the
      administration of oral prednisolone (1 mg/kg) to children admitted to hospital
      with croup from the ED. The secondary objective was to determine whether children
      with mild croup had a more rapid resolution of SAR. METHODS: This was a
      retrospective explicit chart review of all children admitted to the paediatric
      ward of a community, paediatric teaching hospital with a diagnosis of croup over
      one year. Data collected included patient demographics, Westley and Geelhoed
      croup scores on presentation to the ED and the duration of SAR after
      administration of steroids. RESULTS: For the 188 cases analyzed, median duration
      of SAR was 6.5 h (95% CI 6-7 h, range 0.5-82 h). Children with a Westley score of
      < or = 2 or a Geelhoed score of < or = 3 had a shorter duration of SAR than those
      with higher scores (6 h vs. 7 h, P < 0.05), which although statistically
      significant is unlikely to be of clinical significance. CONCLUSIONS: Stridor at
      rest resolves promptly after the administration of oral steroids in the vast
      majority of cases. This suggests that a subset of patients previously admitted to
      hospital with croup may be able to be treated and discharged from the ED.

PMID- 15239729
TI  - A paediatric trauma study of scooter injuries.
AB  - OBJECTIVE: To investigate the incidence and describe the nature of non-motorized
      scooter related injuries in children presenting to the ED. SETTING: Paediatric ED
      of a metropolitan tertiary referral hospital. METHODS: A prospective
      observational study of patients aged under 19 years presenting with injuries
      sustained while using a non-motorized scooter. Clinicians recorded the data in
      the patient record. MAIN OUTCOME MEASURES: type of injury sustained; period of
      experience on the scooter; the use of protective gear; the presence of adult
      supervision; the place of accident; and the patient outcome. RESULTS: Sixty-two
      eligible patients were recruited over an 18 month period. The incidence of
      scooter- related injuries was 1.3% of all paediatric trauma presentations. There
      was a fall in scooter injury presentations over the study period; however, this
      was not statistically significant. The most common injury sustained using a
      scooter was an upper limb fracture (41.9%). Closed head injury comprised 8.1% of
      all scooter related injuries. The majority of patients were not wearing
      protective gear and were unsupervised at the time of their accident. Most
      patients (79%) were managed in the ED and discharged. CONCLUSIONS: There has been
      no significant change in scooter injury presentations over the two summer periods
      of 2000 and 2001. Children presenting to the ED with a scooter related injury
      tend to be primary school aged, which may have implications on scooter design,
      age recommendations and safety guidelines.

PMID- 15239730
TI  - Prolonged pre-procedure fasting time is unnecessary when using titrated
      intravenous ketamine for paediatric procedural sedation.
AB  - BACKGROUND: Paediatric procedural sedation (PPS) is a common procedure in most
      general EDs. Many departmental guidelines suggest mandatory fasting times for
      children undergoing PPS, in an attempt to decrease the incidence of postoperative
      vomiting and (theoretically) aspiration pneumonitis, despite there being little
      or no evidence in the literature to support these mandatory fasting times.
      OBJECTIVES: To prospectively address the relationship between preprocedure
      fasting time and intraprocedure or postprocedure vomiting in children aged 1-12
      years undergoing procedural sedation with intravenous ketamine in the ED.
      METHODS: From January 1999 to May 2000 all children presenting to the Royal
      Darwin Hospital Emergency Department with a condition requiring ketamine PPS were
      enrolled for data collection after parental consent was obtained. Titrated
      intravenous ketamine was administered via protocol. Prospective ED procedural
      sedation data collection forms of 272 consecutive cases of titrated intravenous
      ketamine sedation were reviewed. RESULTS: Fasting time was accurately recorded on
      257 (95%) data collection forms. There was no intraprocedure vomiting. Overall
      rate of postprocedure vomiting was 13.9%. No statistically significant
      association between decreased fasting time and increased incidence of vomiting
      was found. In fact, there was a trend towards increased incidence of vomiting
      with increased fasting time (P = 0.08). The rate of vomiting of those children
      fasted 3 h or greater preprocedure (20/127 or 15.8%) was over twice the rate of
      those fasted less than 1 hour (2/30 or 6.6%). Incidence of vomiting was
      significantly associated with increasing age (P = 0.0007). No clinically evident
      aspiration pneumonitis occurred. CONCLUSION: Prolonged preprocedure fasting time
      did not reduce the incidence of postprocedure vomiting in this case series; to
      the contrary there was a increased incidence of vomiting with longer fasting
      times (P = 0.08). There was an increase in postprocedure vomiting with increasing
      age of the patients.

PMID- 15239732
TI  - Mental health and alcohol and other drug training for emergency department
      workers: one solution to help manage increasing demand.
AB  - OBJECTIVE: To evaluate a training course for ED staff aiming to improve knowledge
      and skills in working with mental health and drug/alcohol patients attending EDs.
      METHODS: Pre- and postcourse questionnaires assessed attitudes and self-ratings
      of confidence, knowledge and skills in working with these patients. Follow-up
      interviews assessed if new skills or approaches to patient management had been
      integrated into daily ED practice. RESULTS: Little change was observed in the
      course participants' attitudes, although reported attitudes were generally
      appropriate. Self-ratings of confidence in skills and knowledge showed a
      significant improvement on all questions following the course. Responses to the
      follow-up interviews suggest course information has been retained and integrated
      into practice, especially in conducting triage and other assessments and taking
      more time to talk to patients. CONCLUSION: The course has led to staff feeling
      more confident and competent to help mental health or drug/alcohol patients who
      attend the ED.

PMID- 15239731
TI  - Where to now with carbon monoxide poisoning?
AB  - The controversy regarding the role of hyperbaric oxygen (HBO) in the treatment of
      carbon monoxide (CO) poisoning has been re-ignited following the publication of a
      further randomized controlled trial by Weaver et al., the results of which appear
      to conflict with our findings. Comparative analysis suggests that the apparent
      outcome differences may be secondary to the design, analysis and interpretation
      of the results of the two studies. Following careful analysis of these two papers
      and further results from a study by Raphael et al on 385 CO-poisoned patients, we
      can still find no convincing evidence favouring HBO therapy. Pending further
      research to determine optimal oxygen therapy for CO-poisoning, current therapy
      should involve stratifying patients for risk of a poor outcome. This
      stratification may be aided by the evolving availability of biochemical markers
      of brain injury and the finding that patients with transient loss of
      consciousness and poor performance on neuropsychological tests of the supervisory
      attention system are at higher risk of neuropsychological sequelae. We propose
      that those patients most at risk be admitted and receive more prolonged
      normobaric oxygen therapy whilst those with more minor CO-poisoning should be
      provided with normobaric oxygen of no less than 6 h duration and certainly until
      sign and symptom free.

PMID- 15239733
TI  - Developing a decision tree algorithm for the diagnosis of suspected spider bites.
AB  - OBJECTIVE: To develop a diagnostic algorithm (decision tree) to improve the
      ability to identify or predict medically important spider bites (funnel-web and
      redback spiders) from information about the circumstances and initial clinical
      effects of spider bites. METHODS: A dataset of definite spider bites with expert
      identification of all spiders was used from a previous Australia-wide prospective
      study. Spider bites were categorized as: big black spider (BBS), redback spider
      (RED) and other spider (OTH). Big black spider included funnel-web spiders (most
      medically significant), but also other spiders of similar appearance. Fifteen
      predictor variables were based on univariate analysis from previous studies and
      clinical experience. They included information about the circumstances and early
      clinical effects of bites. The data were analyzed using CART (Classification and
      Regression Trees), a 'decision tree' algorithm used to create a tree-like
      structure to describe a data set. RESULTS: Of 789 spider bites there were 49
      (6.2%) bites by BBS, 68 (8.6%) bites by RED and 672 (85.2%) bites by OTH. A
      decision tree was developed that included six predictor variables (fang
      marks/bleeding; state/territory; local diaphoresis; month; time of day; and
      proximal or distal bite region). The decision tree accurately classified 47 out
      of the 49 (96%) BBS, and no funnel-web spiders were incorrectly classified (100%
      sensitivity). Two hundred and forty-four of 789 were classified as OTH and
      included no BBS. CONCLUSIONS: A decision tree based on a small amount of
      information about the circumstances and early clinical effects of spider bites
      safely predicted all funnel-web spider bites. Application of this algorithm would
      allow the early institution of appropriate treatment for funnel-web spider bites
      and the immediate discharge of 31% as other spider bites (reassurance only).

PMID- 15239734
TI  - Congenital diaphragmatic hernia masquerading as pneumonia.
AB  - Patients with congenital diaphragmatic hernia usually present in the immediate
      neonatal period with respiratory distress. However, presentation beyond the
      neonatal period has sporadically been reported. We report a case of a 4-year-old
      girl who presented with a 1 month history of chronic cough and low-grade fever,
      with no response to multiple antibiotics. Initially, both clinical and
      radiological findings suggested inflammatory chest disease. Fortunately, after
      performing ultrasound, suspicion was raised and she was later diagnosed to have
      left congenital diaphragmatic hernia of Bochdalek type. Although rare, this
      entity should form one of the differential diagnoses of unresolving pneumonia in
      children.

PMID- 15239735
TI  - Postcoital haemoperitoneum: a cause for shock.
AB  - Postcoital haemoperitoneum rarely occurs without evident vaginal injury. A 21
      year-old second gravida woman presented to the ED in shock with a history of 8
      weeks amenorrhoea and abdominal pain of 20 h duration. The ultrasound examination
      revealed a live intrauterine pregnancy and fluid in peritoneal cavity. There was
      a history of coitus 2 hours prior to the onset of pain. At laparotomy, more than
      2 L of free blood was found in the peritoneal cavity. A small bleeding peritoneal
      vessel in pouch of Douglas was identified and ligated.

PMID- 15239736
TI  - An unusual knee injury: Isolated tibiofibular dislocation.
AB  - Isolated proximal tibiofibular dislocation is an extremely rare condition with
      potentially serious complications if missed. The mechanism of injury, clinical
      presentation and treatment options are discussed. This injury was more common in
      previous centuries, when horse riding was the preferred method of transport. The
      young man we present was involved in a pastime that is rising in popularity and
      it is therefore likely that this injury will be a more common presentation to
      EDs.

PMID- 15239741
TI  - Emergency department hazardous material response plan: Staff participation.

PMID- 15239745
TI  - Why buy a medical journal?

PMID- 15239747
TI  - Stress: a badge of honour in the emergency department?

PMID- 15239748
TI  - Emergency department management of maxillofacial trauma.
AB  - This paper highlights critical aspects of examination, diagnosis and early
      management of the maxillofacial trauma patient.

PMID- 15239749
TI  - Vertigo: a practical approach.
AB  - Dizziness is a common symptom and a systematic method is required to make a
      diagnosis from its many possible causes. This article describes an approach to
      the problem with emphasis on true vertigo and in particular its otological
      aetiology. Important points in the history as well as relevant physical signs are
      described together with some readily identifiable conditions and their
      management.

PMID- 15239750
TI  - Management of foreign bodies in the ear, nose and throat.
AB  - This article presents a summary of the common foreign bodies (FB) and a practical
      approach to diagnosis and management. Removal of FB requires good lighting, a
      cooperative or fully restrained patient and a gentle approach by the clinician.
      An accurate diagnosis of the FB should be made prior to attempts to remove it and
      most, if not all FB could be safely removed the following day under better
      lighting conditions, sedation or anaesthesia in a fasted patient by a more senior
      clinician.

PMID- 15239751
TI  - The psychological health of emergency physicians in Australasia.
AB  - OBJECTIVE: To evaluate the psychological health of ACEM Fellows and the important
      factors that impact on this health. METHODS: A cross-sectional, mail survey
      utilizing validated psychological instruments. RESULTS: Three hundred and twenty
      three (63.5%) of 510 physicians responded. Most were recently graduated males.
      Compared to a general population sample, their psychological health was good with
      greater optimism and mastery (P < 0.001), less anxiety, depression and physical
      symptoms (P < 0.001), better life satisfaction (P = 0.04) and similar perceived
      stress (P = 0.20). The mean work stress score (1 = low, 10 = high) was 5.6 +/-
      2.1 (moderate stress) although 63 (19.5%) had very high scores (8-10). The mean
      work satisfaction score was 6.3 +/- 2.1 (moderate satisfaction) although 43
      (13.3%) had very low scores (1-3). Perceptions of control over hours worked and
      mix of professional activities were positively associated with work and life
      satisfaction (P < 0.001) and negatively associated with work stress and measures
      of wellbeing (P < 0.001). Most employed adaptive coping strategies. However,
      maladaptive strategies (alcohol/drugs, denial, disengagement) were positively
      associated with anxiety, depression and stress (P < 0.001). CONCLUSIONS: Most
      physicians are psychologically healthy. However, there appears to be a subgroup
      that is not thriving. Workplace stress should be addressed promptly and greater
      flexibility provided over hours worked and mix of professional activities.

PMID- 15239752
TI  - Workplace factors leading to planned reduction of clinical work among emergency
      physicians.
AB  - OBJECTIVE: There is anecdotal evidence that ACEM Fellows are reducing or planning
      to reduce their clinical workload. We investigated the extent of, and reasons
      for, these reductions. METHODS: An anonymous, cross-sectional postal survey
      utilizing a study-specific questionnaire. RESULTS: Three hundred and twenty-three
      Fellows (63.5%) responded. Most were recently graduated males. In the last 5
      years, the mean number of clinical hours worked per week has reduced
      significantly (P < 0.001) for both junior (40.6-28.9 h) and senior Fellows (30.4
      23.1 h). Further significant (P < 0.001) reductions are planned. The most
      frequently reported reasons for reducing clinical workload were excessive
      workload, family life and emotional health effects, shift work and work stress.
      The most stressful aspects of work reported were access block, dealing with
      management, insufficient staffing, workload pressures and staff supervision.
      Clinical work reportedly impacts most upon family life, social life and emotional
      health. CONCLUSIONS: Fellows are significantly reducing their clinical workload
      largely in response to excessive workload and lack of resources. These findings
      have important implications for professional longevity and work force planning.
      Re-evaluation of workplace practice, especially identified stressors, is
      indicated.

PMID- 15239753
TI  - Compliance with advice and appropriateness of emergency presentation following
      contact with the HealthDirect telephone triage service.
AB  - OBJECTIVE: Evaluation of compliance with advice and appropriateness of emergency
      presentation following contact with a telephone triage service (HealthDirect).
      METHODS: Compliance rates, triage distributions and admission rates were
      determined using linked HealthDirect and ED records for patients living within 2
      km of an ED that presented during 2000. RESULTS: Of 13 019 presentations, 842
      (6.5%) were HealthDirect contacts. In the HealthDirect group there were a greater
      proportion of patients under the age of 15 (290, 34% vs 1598, 13.1%) and women
      (481, 57% vs 5610, 46%). The triage distributions and admission rates for
      HealthDirect contacts and other patients were similar (HealthDirect 37.6%
      admitted, 95% CI 34-41, others 38.4% admitted, 95% CI 38-39, Pchi2 = 0.67). Of
      3996 callers to HealthDirect, 3167 (79%) complied with advice with 963 (61%)
      complying with advice to present and 212 (9%, 95% CI 8-10%) presenting despite
      advice to defer presentation. Triage distributions and admission rates for
      compliers and non-compliers were similar (compliers 38% admitted, 95% CI 34-41,
      non-compliers, 37% admitted, 95% CI 30-44, Pchi2 = 0.89). CONCLUSIONS:
      HealthDirect contacts were of similar appropriateness to non-HealthDirect
      presenters and appear to attend the ED independent of HealthDirect advice.
      HealthDirect has a limited capacity to influence ED utilization or workload.

PMID- 15239754
TI  - Multidisciplinary assessment at triage: a new way forward.
AB  - OBJECTIVE: To evaluate a dual doctor and nurse triage system at a tertiary
      referral hospital. METHODS: Data were compared between periods of
      multidisciplinary triage and periods of standard triage. Data comparison was also
      made between rostered multidisciplinary triage shifts and non-multidisciplinary
      triage shifts. Staff satisfaction with the process was assessed. RESULTS: The
      percentage of patients seen within Australasian Triage Scale performance
      indicator thresholds increased from 75% to 81% in Category 2 patients (P = 0.12)
      and 56% to 78% in Category 3 patients (P < 0.0001). There was a reduction of 50%
      in the number of patients who left prior to being seen by a doctor (P = 0.024).
      Surveys showed high staff satisfaction with the process. CONCLUSIONS: We feel
      that multidisciplinary triage performs a useful function in our department
      enabling us to reduce waiting times. The process is widely accepted amongst the
      staff and it ensures a senior doctor assesses most patients. It reduces the
      number of patients leaving prior to being seen by a doctor and it provides one
      way of getting around access block and a physically small department.

PMID- 15239755
TI  - Pharmacological therapy of acute cardiogenic pulmonary oedema in the emergency
      department.
AB  - This paper critically reviews the major drug types that are currently used in the
      management of acute cardiogenic pulmonary oedema. As decompensated heart failure
      becomes an increasingly common problem in emergency departments in the developed
      world, optimization of emergency drug therapy for these critically ill patients
      is essential. The evidence base for 'routine therapy' in the ED is considered.
      The review also briefly considers emerging pharmacological therapies that may
      have an impact on future management of cardiogenic pulmonary oedema.

PMID- 15239756
TI  - Does the presence of an emergency physician improve access based quality
      indicators in a rural emergency department?
AB  - OBJECTIVE: To assess the effect that the presence of an emergency physician in
      the ED has on the access indicators of the Australian Council on Healthcare
      Standards. METHODS: A retrospective study was carried out in a 265 bed regional
      referral hospital in Victoria. The performance of the ED over a 6 month period,
      during which time there was incomplete emergency physician coverage, was
      monitored using The Australian Council on Healthcare Standards (ACHS) access
      indicators as the benchmark. These indicators are waiting time by triage
      category, and access block. RESULTS: A total of 11 999 patient presentations were
      eligible for inclusion in the study. Emergency physicians were present for 76.5%
      of these presentations. All the indicators show a trend towards improvement when
      an emergency physician was present. However, the only indicator that shows a
      significant improvement is waiting time by triage category, and this is due
      mainly to an improvement within triage category 4. CONCLUSIONS: There is some
      evidence that the presence of an emergency physician improves performance within
      this group of access based indicators within a rural ED, however, the effect seen
      here is small. More studies are needed on this topic and also on the development
      of quality indicators for rural ED.

PMID- 15239757
TI  - Pilot study of metropolitan emergency department workload complexity.
AB  - OBJECTIVE: Assessment of emergency department (ED) patient complexity using the
      number of procedures, investigations or consultations (PICsum). METHODS:
      Retrospective analysis of 12 months of data from an adult metropolitan teaching
      hospital ED. RESULTS: A bimodal distribution of PICsum (modal peaks, PICsum 1 and
      7) was observed in all Australasian Triage Scale, disposition, mode of arrival,
      age and referral source groups. Patients requiring a minimum of two procedures or
      a minimum of two investigations or a minimum of two consultations (Min2 patients)
      comprised 59% (95% CI 58.5-59.5) of total patients 93% (95% CI 92.5-93.8) of
      total PICsum. Age is highly correlated with Mean PICsum (Pearson r = 0.98, P <
      0.001) and the proportion of Min2 patients (Pearson r = 0.98, P < 0.001).
      CONCLUSIONS: An intuitive partition in the complexity distribution is identified
      at up to one procedure, one investigation and one consultation. Patient age is
      correlated with complexity and ED age distribution may be a useful proxy for
      complexity, particularly if used in conjunction with validated age versus
      complexity tables.

PMID- 15239758
TI  - Cyclooxygenase-2 inhibitors: do they have a role in emergency department
      prescribing?
AB  - Cyclooxygenase-2 selective inhibitors (COXIB or CSI) have been released with a
      fanfare as efficacious and safer alternatives to traditional non-steroidal anti
      inflammatory drugs. They purport to offer equivalent degrees of analgesia and an
      improved safety profile. COXIB currently available in Australasia are celecoxib
      (Celebrex), rofecoxib (Vioxx) and etoricoxib (Arcoxia). This review discusses the
      pharmacology of these agents and reviews recent literature regarding their
      effectiveness and safety. It endeavours to answer the question 'Should we be
      using COXIB in emergency departments in Australasia'?

PMID- 15239759
TI  - Clinical effects of exposure to the White-stemmed gum moth (Chelepteryx collesi).
AB  - BACKGROUND: The White-stemmed gum moth (Chelepteryx collesi) can be found in
      eastern Australia. The clinical effects of injuries caused by its many spine-like
      hairs are poorly defined and concern about the numerous hairs that remain
      embedded following contact with the cocoon have led to heroic means of removal.
      OBJECTIVE: To examine the clinical effects of injuries by the caterpillar or
      cocoon of the White-stemmed gum moth. METHODS: Prospective observational study of
      caterpillar injuries from calls to the New South Wales Poisons Information
      Centre. Cases resulting from C. collesi exposure were included for analysis.
      Caterpillars and cocoons were expertly identified where available and a follow-up
      consultation of all patients was conducted. Information was collected on the
      circumstances of exposure, local and systemic effects and treatment. RESULTS:
      From the 26 included cases, seven had confirmed caterpillar contact (all children
      aged 1-11), six had confirmed cocoon contact and 13 had exposures consistent with
      C. collesi, but no caterpillar was caught. All cases occurred in summer. Of 13
      confirmed exposures there was no difference between caterpillars and cocoons, and
      these were considered together. Affected areas were hands, feet, or both,
      following C. collesi being handled or trodden on. Pain was reported in all 13
      cases, one with severe pain. In 10 cases pain duration was < 60 min. Six subjects
      had more than 100 hairs embedded (small black dots). In three cases, the hairs
      were surrounded by swelling and yellow discolouration. Despite the attempted
      removal of multiple hairs, they remained embedded for prolonged periods but
      caused no sequelae. CONCLUSION: The clinical effects of the White-stemmed gum
      moth were minor with local pain. Although hairs remained in all cases, they
      caused no problems. Complete removal of hairs is neither possible nor necessary,
      and painful and invasive methods should be avoided.

PMID- 15239761
TI  - Field Guide to Wilderness Medicine, 2nd edition.

PMID- 15239760
TI  - Anaphylaxis to trimethoprim: an under-appreciated risk in acute medical care.
AB  - Anaphylaxis is a severe, systemic allergic reaction, which is frequently
      unexpected and carries a high mortality risk as a medical emergency. Anaphylaxis
      to trimethoprim is not a well recognized event. Since trimethoprim represents the
      leading antibiotic for the treatment of urinary tract infections, its potential
      to cause anaphylaxis needs to be recognized, whether alone or as the 'active'
      ingredient in cotrimoxazole (trimethoprim-sulphamethoxazole combination), by
      those prescribing it and those providing acute care. A case of probable
      anaphylaxis following trimethoprim ingestion is presented with discussion
      supporting its potency including evidence at an immunological level highlighting
      its under-appreciated risk in acute medical care.

PMID- 15239762
TI  - Emergent Field Medicine.

PMID- 15239763
TI  - Goldfrank's Toxicologic Emergencies, 7th edition.

PMID- 15239764
TI  - Emergency Pediatrics: A Guide to Ambulatory Care, 6th edition.

PMID- 15239765
TI  - Emergency Medicine Clinics of North America -'Bioterrorism'

PMID- 15239766
TI  - Occupational, Industrial, and Environmental Toxicology, 2nd edition.

PMID- 15239767
TI  - Emergency Medicine Secrets, 3rd edition.

PMID- 15239768
TI  - Unethical authorship practices.

PMID- 15239769
TI  - Do differences exist in treatment and outcome for women with STEMI in Australia?

PMID- 15239771
TI  - Reply.

PMID- 15239770
TI  - Don't forget the A in eclampsia.

PMID- 15239772
TI  - Acute urinary retention secondary to kava ingestion.

PMID- 15239773
TI  - Peer Review: February 2004.

PMID- 15239774
TI  - Peer Review.

PMID- 15239775
TI  - Periodontal epidemiology: towards social science or molecular biology?
AB  - Terms such as 'molecular epidemiology' and 'genetic epidemiology' have been
      coined to depict the change from 'traditional epidemiology', concerned with
      disease determinants at the community or society level, over to 'modern
      epidemiology', which is concerned with determinants operating at the individual
      level or even below, i.e. at the organ, tissue, cell, or molecular level. In this
      commentary, we point out to the limitations of this development and suggest that
      more emphasis is placed on making the presumed causal disease models explicit,
      when investigating the relationship between putative determinants and disease.
      Understanding the disease processes at the micro-level is insufficient for
      understanding disease at the individual level; and disease patterns at the
      population level cannot be understood unless it is realized that individuals
      exist in a variety of contexts that cannot be reduced to individual attributes.

PMID- 15239776
TI  - Dental fear in adults: a meta-analysis of behavioral interventions.
AB  - OBJECTIVES: The aim of this meta-analytic and systematic quantitative approach is
      to examine the effects of behavioral interventions for dental anxiety and dental
      phobia. METHODS: Eighty studies were identified where dental fear treatment with
      behavioral methods was evaluated. Thirty-eight of 80 met entry criteria and were
      included in a meta-analysis. RESULTS: The calculated effect sizes (ESs) for self
      reported anxiety after intervention indicate positive changes in 36 of the 38
      studies and no changes in two. The overall ES = 1.8 (95% CI: 1.6, 1.8). The
      percent of subjects with post-treatment dental visits in the first 6 months post
      treatment varied between 50 and 100%. The overall ES for attendance at dental
      visits, weighted by sample size, is 1.4 (95% CI: 1.3, 1.6). The homogeneity
      analysis indicates that the studies cannot be adequately described in one ES. The
      reported percentage of subjects with a dental visit between 6 months and 4 years
      post-treatment varied from 48 to 100%. The overall weighted ES for visiting the
      dentist, adjusted for drop-outs in the studies, is 1.2 (95% CI: 0.99, 1.4).
      CONCLUSIONS: Despite extensive heterogeneity, changes in self-reported anxiety
      represent medium to large ESs. Patients signing up for a behavioral intervention
      for dental fear can be expected to report a significant reduction in their fear,
      and this effect generally seems to be lasting. Mean long-term attendance ( >4
      years after treatment) is 77%.

PMID- 15239777
TI  - An ecological study of caries experience, school performance and material
      deprivation in 5-year-old state primary school children.
AB  - AIM: To investigate whether measures of school performance and socioeconomic
      circumstances could be used as indicators of caries experience in 5-year-old
      Wandsworth state primary schoolchildren. DESIGN: An ecological study using
      aggregated caries data collected in the British Association for the Study of
      Community Dentistry (BASCD) Oral Health Survey of 5-year-old children (2001),
      Jarman scores generated from national census data and matched by school postcodes
      (1991), school performance results in English, mathematics and Linguistic
      Awareness of Reading Readiness test (LARR; literacy) and free school meals
      recipient data from the Local Education Authority, Research and Evaluation Unit
      (2001). SETTING: State primary schools in the London borough of Wandsworth, UK.
      SUBJECTS: All 55 Wandsworth state primary schools including 1968 5-year-old
      pupils. OUTCOME MEASURE: The school mean dmft score. RESULTS: Simple linear
      regression analysis demonstrated that school mean dmft was statistically
      significantly associated with all five explanatory variables: English (P =
      0.001), mathematics (P = 0.002), LARR (P < 0.001), the percentage of children
      receiving free school meals (P < 0.001) and the school address Jarman score (P =
      0.02). Stepwise multiple linear regression identified the LARR score and the
      percentage of children receiving free school meals as the strongest indicators of
      school mean dmft score explaining 41% of the variation in school mean dmft score.
      CONCLUSION: Early school performance results in English, mathematics and LARR,
      the percentage of children receiving free school meals and school address Jarman
      scores were good indicators of school mean dmft scores in 5-year-old children in
      the Wandsworth state primary schools.

PMID- 15239778
TI  - Can nonstandardized bitewing radiographs be used to assess the presence of
      alveolar bone loss in epidemiologic studies?
AB  - OBJECTIVE: To compare periodontitis-associated alveolar bone loss assessment by
      standardized and nonstandardized radiographs in clinical and epidemiologic
      studies. METHODS: Participants included 37 patients aged 21-66 years with prior
      nonstandardized bitewing radiographs scheduled to receive bitewing radiographs as
      part of their next routine dental care visit. Standardized bitewing radiographs
      were taken with a Rinn film holder to position the film in the mouth and align
      the X-rays so that they were at 90 degrees to the film. Before taking the
      radiograph the bite was registered in centric relation using a polyether
      impression material. One registered dental hygienist took and processed all the
      standardized radiographs. One dentist read all radiographs using a viewing box,
      magnifying lens, and periodontal probe with William's markings. Radiographic bone
      loss was measured to the closest millimeter at mesial and distal sites of the
      posterior teeth excluding third molars. The examining dentist was blinded to the
      participant's name, age, gender, or if the radiograph was standardized or
      nonstandardized. RESULTS: Mean bone loss (+/- SD) was similar in the standardized
      and nonstandardized groups (1.60 +/- 0.72 mm versus 1.64 +/- 0.85 mm), and the
      correlation was high (r = 0.95). Periodontitis was defined as present if the
      participant had at least one site with 3, 4 and 5 mm bone loss. The Kappa
      statistics for concordance using these three cutoffs were good and ranged from
      0.60 to 0.65. The sensitivity ranged from 72.7 to 80.8% and specificity from 88.5
      to 90.9%. CONCLUSIONS: Periodontitis assessed as mean alveolar bone loss or the
      prevalence of disease based on alveolar bone loss can be accurately and reliably
      evaluated from nonstandardized radiographs.

PMID- 15239779
TI  - Caries decline in the primary dentition of Belgian children over 15 years.
AB  - OBJECTIVES: (1) To investigate changes in caries prevalence in the primary
      dentition of children resident in Brussels, Belgium between 1983 and 1998, (2) to
      analyse associations between changes in caries and children's socioeconomic and
      ethnic aspects. METHODS: In the Brussels region, children in the first grade at
      the same schools were sampled in cohort 1983 (n = 396) and cohort 1998 (n = 473).
      Caries experience of Belgian and non-Belgian nationals was summarized in dmf
      scores. The socioeconomic status of the children was established based on their
      parents' education and profession. The children were categorized in eight
      subgroups in relation to their socioeconomic status, ethnic origin and cohort
      (SESEC subgroups). RESULTS: The percentage of caries-free children increased
      significantly from 31.5% to 47.5%. A reduction was observed in the dmft scores
      from 3.9 to 2.3 (P < 0.001) and in the dmfs scores from 6.9 to 5.0 (P < 0.001).
      The odds ratio of being caries-free was 2.5 times higher for privileged children
      and 2.3 times higher for children belonging to cohort 1998. The ANCOVA analyses
      revealed that most of the SESEC subgroups showed significant reduction in dmft
      scores from 1983 to 1998 (P < 0.003). CONCLUSIONS: Children resident in Brussels
      showed caries decline in their primary dentition over 15 years. Diversity in
      caries decline was associated with children's socioeconomic status and ethnic
      origin.

PMID- 15239780
TI  - Consumption of nonpublic water: implications for children's caries experience.
AB  - There are concerns that the consumption of unfluoridated bottled and tank water
      may put children at increased risk of developing caries. OBJECTIVES: The aim of
      this study was to investigate the relationship between nonpublic water
      consumption (either from bottles or rainwater tanks) and socioeconomic status
      (SES) and both deciduous and permanent caries experience. METHODS: A random
      sample of children enrolled in the School Dental Service of South Australia
      participated in the study (response rate = 71.8%, n = 9988). RESULTS: Forty-five
      per cent of children had greater than 50% lifetime consumption of nonpublic water
      while 36% of children had 0% lifetime consumption. Increased use of nonpublic
      water occurred for children from lower socioeconomic groups, two-parent families
      and children from nonmetropolitan areas, with these results most likely a result
      of the residential location of the children. Multivariate modelling revealed a
      significant positive relationship between deciduous caries experience and
      consumption of nonpublic water, even after controlling for the age and sex of the
      child, SES and residential location. This relationship was significant only for
      those children with 100% lifetime availability of fluoridated water. The effect
      of consumption of nonpublic water on permanent caries experience was not
      significant. It is postulated that these findings may result from the lower
      caries activity in the permanent dentition of children aged 10-15 and possible
      dietary confounders. CONCLUSION: Recommendations are made for the addition of
      fluoride to bottled water, especially with regard to the oral health of younger
      children.

PMID- 15239781
TI  - Complete dentures and oral health-related quality of life -- do coping styles
      matter?
AB  - Oral health-related quality of life (OHRQOL) in edentulous patients with complete
      dentures is often impaired. This paper investigates the effect of different
      coping styles on OHRQOL. PURPOSE: (a) To assess OHRQOL of edentulous patients
      with conventional complete dentures, and (b) to investigate if individual
      differences in these patients' styles of coping with stress affect their OHRQOL.
      MATERIALS AND METHODS: Data were collected from 249 fully edentulous patients
      with complete dentures (mean age: 66.0 years) who responded to a mailed survey
      (adjusted response rate: 48.8%). OHRQOL was measured with the 14-item short form
      of the oral health impact profile (OHIP). Ratings of coping strategies were
      obtained using the 28-item Brief COPE, an instrument measuring various styles of
      coping with stress. Linear regression analyses were used to explore the
      relationships between coping styles, background variables such as age, gender,
      income, and age of prosthesis, and the patients' OHRQOL. RESULTS: About 35% of
      the respondents reported impacts from their oral conditions on their overall
      OHRQOL (OHIP-14 total score) occasionally, fairly often, or often. Physical pain
      was even more prevalent, with 53.3% of the respondents reporting pain impacts.
      The linear regression model (P < 0.0001) explained 31.1% of the variation in the
      OHIP-14 total score. The coping variables instrumental support, behavioral
      disengagement, substance abuse, denial, and religion were significant negative
      predictors of OHRQOL. Only emotional support was a significant positive predictor
      of OHRQOL. CONCLUSION: Wearing conventional complete dentures has a significant
      impact on OHRQOL. This impact is moderated by the styles a patient uses to cope
      with stress. Using emotional support has a positive effect on OHRQOL, while other
      coping styles, namely instrumental support, behavioral disengagement, substance
      abuse, denial, and religion are significant negative predictors of OHRQOL.

PMID- 15239782
TI  - Reported bruxism and biopsychosocial symptoms: a longitudinal study.
AB  - OBJECTIVES AND METHODS: In this follow-up study of 30-50-year-old employees (n =
      211) of the Finnish Broadcasting Company (YLE), respondents completed
      questionnaires in both 1999 and 2000 containing items on demographic data,
      tobacco use, levels of perceived bruxism, affective disturbance, sleep
      disturbance, somatic symptoms, pain symptoms and temporomandibular disorder (TMD)
      symptoms. RESULTS: Bruxism was significantly more prevalent among smokers (P =
      0.005). Age, marital status, and gender were not associated with bruxism.
      Subjects in the frequent bruxism group (n = 74) reported the TMD-related painless
      symptoms, affective disturbance and early insomnia significantly more often than
      average. In the multivariate analyses, clustered pain symptoms (P = 0.001), TMD
      related painless symptoms (P = 0.004) and smoking (P = 0.012) were significantly
      positively associated with frequent bruxism, when the independent effects of age
      and gender were controlled for. CONCLUSIONS: It was concluded that successful
      management of TMD necessitates smoking cessation, as tobacco use may both amplify
      the patient's pain response and provoke bruxism. Psychosocial factors and
      perceived stress should not be ignored, however.

PMID- 15239783
TI  - A follow-up study of the use of DIAGNOdent for monitoring fissure caries in
      children.
AB  - OBJECTIVES: The aim of this study was to evaluate the utility of the laser
      fluorescence device DIAGNOdent for monitoring occlusal caries longitudinally as
      part of a routine dental check-up in a public dental clinic. METHODS: Children
      aged 7-8 and 13-14 years at baseline participated in the study. As part of two
      consecutive dental check-ups with a mean interval of 1,19, years, 423 permanent
      molars and 315 primary molars in 81 children were examined visually and using
      DIAGNOdent by one dentist. In teeth where, as judged by visual examination,
      caries had emerged or progressed during the follow-up, the DIAGNOdent values had
      increased significantly from the baseline. RESULTS: In permanent teeth with a
      change in visual score from sound to enamel or dentin caries, the mean DIAGNOdent
      value increased from 24 to 37 and in primary teeth from 8 to 40. The increase in
      DIANGOdent values correlated positively with the increase in visual score. The
      mean DIAGNOdent value at baseline was significantly higher in teeth that became
      carious than in those that remained sound during the follow-up. For permanent
      teeth with a visual reversal from inactive or active enamel caries to a sound
      surface, the mean DIAGNOdent value decreased from 36 to 24. CONCLUSIONS: These
      results suggest that DIAGNOdent is useful in monitoring occlusal caries in both
      permanent and primary molars.

PMID- 15239784
TI  - Ductoscopy: defining its role in the management of breast cancer.

PMID- 15239786
TI  - A review of mammary ductoscopy in breast cancer.
AB  - Breast carcinoma and hyperplasia are thought to start in the lining of the breast
      duct. Mammary ductoscopy is an emerging technique allowing direct visual access
      of the ductal system of the breast through the nipple. This article reviews and
      discusses the utility of mammary ductoscopy. Abnormalities can be identified
      successfully by mammary ductoscopy, and intraductal biopsy can be used when the
      tumor is a polypoid type. Ductal lavage using microcatheters is effective in
      identifying malignant cells in high-risk women and this has stimulated interest
      in exploring the role of mammary ductoscopy in breast cancer screening. Mammary
      ductoscopy combined with ductal lavage may have a role in the management of
      patients with nipple discharge, the guiding of breast-conserving surgery for
      cancer, and in screening for high-risk women. The addition of molecular and
      genetic analysis of cells obtained by mammary ductoscopy are likely to enhance
      the use of this technique. Mammary ductoscopy techniques are safe and appear
      useful for detecting abnormalities in the breast. The additional molecular
      biologic study or ductal lavage may enhance the ability to direct and limit
      subsequent surgery when removing the offending lesions.

PMID- 15239787
TI  - Mammographic screening and disease presentation of breast cancer patients who die
      of disease.
AB  - This retrospective study assesses the presentation of breast cancer patients who
      died of disease. The goal was to estimate the proportion of patients whose cancer
      was detected by a screening mammogram, yet still proved fatal, and to
      characterize contemporary fatal breast cancers. Patients who died of breast
      cancer between 1995 and 2001 and were treated at three hospitals with complete,
      accessible information were identified using the Rhode Island Department of
      Health database and State Cancer Registry. Patients were classified as routinely
      screened, true interval, off-program, or unscreened. The median maximum diameter
      of fatal cancers was 2.5 cm. Sixty-nine percent of patients had lymph node
      metastases and 19% had stage IV disease. Fifty-seven percent were unscreened and
      12% were routinely screened, with 2.5 cm and 1.5 cm median tumor diameters,
      respectively. Fifty-two percent of unscreened patients and no routinely screened
      patients had stage III or IV disease. Fifteen percent of fatal cancers were
      interval cancers. Only 27% of patients who died of breast cancer were
      participants in routine screening programs in Rhode Island, where 84% of women
      receive regular mammograms. This study complements randomized, population-based
      trials demonstrating a significant mortality reduction with an invitation to
      participate in screening.

PMID- 15239788
TI  - Contralateral breast cancer: factors associated with stage and size at
      presentation.
AB  - Few reports have evaluated factors associated with the stage at presentation of
      contralateral breast cancer and whether contralateral cancer presentation has
      changed in recent years, during which increased screening and enhanced adjuvant
      therapy of the initial tumor has been introduced. Patients with initial cancers
      staged 0-IIIB diagnosed between 1980 and 1999 who subsequently developed
      contralateral breast cancer were evaluated for stage, primary tumor size and
      histologic features, patient age and year of diagnosis, synchronous or
      metachronous presentation, and time from initial tumor to diagnosis of
      contralateral breast cancer. Tumor presentation was compared with
      contemporaneously diagnosed unilateral breast cancer patients. A total of 171
      patients were diagnosed with contralateral breast cancer; 161 cases if lobular
      carcinoma in situ for either the initial or the contralateral tumor were
      excluded. Contralateral tumors were of significantly smaller size and of earlier
      stage than initial tumors. Contralateral cancers demonstrated earlier stage
      distributions with more recent year of diagnosis; initial tumors in contralateral
      patients did not. Earlier stage at presentation of contralateral tumors was
      associated in a multivariate model with more recent year of contralateral tumor
      diagnosis and earlier stage at presentation of the initial tumor; contralateral
      tumor size was associated with the size of the initial tumor. More recently
      diagnosed contralateral breast cancers are presenting with earlier stages of
      disease. The stages of initial tumors in these patients have not undergone such
      an improvement. Initial tumor size and stage is strongly associated with
      contralateral breast cancer size and stage; this association is independent of
      the year of diagnosis. Increased compliance with screening might be expected to
      improve both initial tumor stage and tumor size presentations in contralateral
      tumor patients, as well as the presentation of contralateral cancers.

PMID- 15239790
TI  - Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies.
AB  - Idiopathic granulomatous mastitis is a rare disease of the breast. Clinically and
      radiologically it may mimic breast carcinoma. Awareness of surgeons,
      pathologists, and radiologists is essential to avoid unnecessary mastectomies.
      Data regarding 24 patients with histologically confirmed idiopathic granulomatous
      mastitis treated at our center over 8 years were analyzed. The mean age of
      patients was 34.3 years. Breast lump was the most common presentation. The right
      breast was affected in 16 cases. Four patients were pregnant at the time of
      presentation. Lactation within 6 months of presentation was documented in four
      patients. Two patients used contraceptives pills. A clinical suspicion of
      malignancy was present in 17 cases. Mammography was performed in 16 patients and
      showed focal asymmetrical dense lesions in 9, well-circumscribed opacity in 4,
      spiculated lesion in 1, and was normal in 2. Fine-needle aspiration was performed
      in 17 patients, of which 2 were reported as malignant. Wide local excision was
      the mainstay of treatment. One patient underwent mastectomy upon clinical,
      mammographic, and repeated cytologic findings consistent with malignancy, and the
      final histology confirmed idiopathic granulomatous mastitis with no evidence of
      malignancy. Four patients developed recurrence after a mean follow-up of 31.2
      months. A greater awareness of the rare entity of idiopathic granulomatous
      mastitis is mandatory to avoid unnecessary mastectomies. Clinical, radiologic,
      and even cytologic findings are sometimes confused with malignancy. To the best
      of our knowledge, our patient who developed the disease at the age of 11 years is
      the youngest reported case.

PMID- 15239789
TI  - Relationship between mammographic breast density and tamoxifen in women with
      breast cancer.
AB  - Previous studies have reported that tamoxifen use is associated with a decrease
      in mammographic breast density. This is a potentially valuable finding since
      mammographic sensitivity is limited by breast density. Anything that reduces
      breast density would theoretically enhance the sensitivity of mammography for the
      detection of breast cancer in women at an earlier stage when it is more curable.
      We performed a retrospective study investigating the potential effect of
      tamoxifen on breast density. The data for this retrospective study were collected
      from the records of 52 charts from a single medical oncologist. Patients with
      breast cancer were selected regardless of stage or age at the time of diagnosis
      or treatment, as long as their charts had records of bilateral mammograms. For
      each breast on each woman, both mediolateral oblique and craniocaudal views were
      reviewed independently by two radiologists on two separate occasions to obtain
      inter- and intraobserver variability. Two methods of classifying breast density
      were used: the Breast Imaging Reporting and Data System (BI-RADS), and
      measurements of percent density. Only age and menopausal status were found to be
      associated with breast density. There was no correlation between breast density
      and tamoxifen use (past or present). Our study shows no association between
      tamoxifen use and breast density. We confirm previous observations that breast
      density is inversely correlated with age and postmenopausal status.

PMID- 15239792
TI  - The effect of supraphysiologic levels of iodine on patients with cyclic
      mastalgia.
AB  - A randomized, double-blind, placebo-controlled, multicenter clinical trial was
      conducted with 111 otherwise healthy euthyroid women with a history of breast
      pain. Patients had to document moderate or severe breast pain by recording a
      score > or =5 on a visual analog scale (VAS) of pain for > or =6 days per cycle
      and had to present with fibrosis involving at least 25% of both breast surfaces.
      Subjects could not be effectively treated with more conservative measures such as
      local heat or nonprescription analgesics. There was not a statistically
      significant difference in the dropout rate for patients on placebo (11.8%), 1.5
      mg/day (31.3%), 3.0 mg/day (18.4%), or 6.0 mg/day (25%) of molecular iodine for 6
      months. Physicians assessed breast pain, tenderness, and nodularity each cycle;
      patients assessed breast pain and tenderness with the Lewin breast pain scale at
      3-month intervals and with a VAS at each cycle. A statistically significant
      improvement (p < 0.01) associated with dose was observed in the Lewin overall
      pain scale for all treated groups compared to placebo. Reductions in all three
      physician assessments were observed in patients after 5 months of therapy in the
      3.0 mg/day (7/28; 25%) and 6.0 mg/day (15/27; 18.5%) treatment groups, but not
      the 1.5 mg/day or placebo group. Patients recorded statistically significant
      decreases in pain by month 3 in the 3.0 and 6.0 mg/day treatment groups, but not
      the 1.5 mg/day or placebo group; more than 50% of the 6.0 mg/day treatment group
      recorded a clinically significant reduction in overall pain. All doses were
      associated with an acceptable safety profile. No dose-related increase in any
      adverse event was observed.

PMID- 15239791
TI  - Expression of c-kit proto-oncogene product in breast tissue.
AB  - The proto-oncogene c-kit encodes a transmembrane tyrosine kinase growth factor
      receptor. Stem cell factor, the receptor ligand, plays an important role in the
      development of certain neoplasms. c-kit is selectively and competitively bound by
      STI-571, a newly developed tyrosine kinase inhibitor. Several investigators
      report conflicting results concerning its expression, especially in malignant
      breast lesions. The objective of this study was to better characterize the
      expression of c-kit within the spectrum of breast epithelium (normal breast
      epithelium, nonneoplastic lesions, and breast carcinoma). Seventy-seven randomly
      selected breast tissue samples, each containing normal breast epithelium (21),
      invasive breast carcinoma (41), in situ breast carcinoma (29), papilloma (8),
      fibroadenoma (5), fibrocystic change (11), and/or metastatic breast carcinoma
      (4), were immunostained with polyclonal rabbit antihuman c-kit (Dako,
      Carpenteria, CA) at a dilution of 1:200. The staining was interpreted as negative
      if no cells were immunoreactive, weak positive if 5% of the cells were
      immunoreactive, and positive if more than 5% of the cells were immunoreactive.
      Appropriate positive and negative controls were used. The observed staining was
      cytoplasmic, with highlighting of the nuclear membrane. Normal breast epithelium
      was positive in all cases. More than half of the cases of hyperplastic changes
      and benign neoplasms (fibroadenoma and papilloma) were positive. Only 10% of
      invasive and in situ carcinomas showed positivity for c-kit. c-kit is
      consistently expressed in normal breast epithelium, variably expressed in benign
      breast lesions, and poorly expressed in breast carcinoma. These data suggest that
      c-kit may play a role in breast tumor progression and may therefore have
      diagnostic, prognostic, and therapeutic implications.

PMID- 15239793
TI  - Sentinel lymph node biopsy for breast cancer: improvement in results over time.
AB  - Many modifications in the technique of sentinel lymph node (SLN) biopsy for
      breast cancer have taken place since it was first introduced. This analysis was
      undertaken to determine, in a large multi-institutional study, whether SLN biopsy
      results have improved over time. Patients with clinical stage T1-2, N0 breast
      cancer were enrolled in this prospective study between August 1997 and February
      2002. SLN biopsy was performed using blue dye and/or radioactive colloid along
      with completion level I/II axillary dissection in all patients. The majority of
      subjects included in this study represent the surgeons' initial experience with
      SLN biopsy for breast cancer. Statistical comparison of the SLN identification
      (ID) rate and false-negative (FN) rate were performed by chi-squared analysis. A
      total of 3370 subjects from 300 surgeons were enrolled in the study. Collectively
      the SLN ID rate, as well as the mean number of SLNs removed per patient has
      improved, while the FN rate has remained fairly constant over time. The improved
      ID rate may be related to improved technical details, while the FN rate has not
      changed significantly. This highlights the ongoing need for surgeons to perform
      backup axillary dissection during their initial learning phase.

PMID- 15239794
TI  - Reduction of discomfort during mammography utilizing a radiolucent cushioning
      pad.
AB  - The purpose of this study was to evaluate the use of a radiolucent cushioning pad
      during routine screening mammography to determine the degree of reduction in
      discomfort, any correlation of that reduction with various clinical factors, and
      the pad's impact on image quality, compression force, and radiation dose. A total
      of 512 patients presenting for routine screening mammography were evaluated. The
      radiolucent cushioning pads (MammoPad, Biolucent Inc., Aliso Viejo, CA) were
      placed on the bucky and compression paddle of the mammographic equipment (M-IV,
      Lorad Corp., Danbury, CT). For each patient, the radiolucent pads were used for
      imaging one breast while the opposite breast, which served as a control, was
      imaged without the pads. In all patients, the breast was positioned and
      compressed in standard fashion, using routine craniocaudal (CC) and mediolateral
      oblique (MLO) views. Patients completed a questionnaire before and after the
      mammogram. A visual analog scale (VAS) was used to record anticipated discomfort
      as well as the discomfort experienced during compression with and without the
      pads. Age, hormone replacement status, prior experience with mammography,
      compression force, and breast composition were recorded, as were dose parameters
      (mAs and kVp), from which midglandular dose values were calculated. On the side
      where the pads were used to cushion the breast, 73.5% (371/505) of women
      experienced a significant decrease in discomfort. Of those who benefited, there
      was a 47% decrease in discomfort. On the pad side, compression force was
      increased an average of 14%, and there was a 4% decrease in dose for the CC view
      and no increase in dose for the MLO view. When comparing benefit versus
      nonbenefit groups, a significant reduction in discomfort did not correlate with
      any of the clinical factors evaluated, with the exception of experienced
      discomfort reported after the mammogram. Use of the MammoPad radiolucent cushion
      on the bucky and compression paddle was an effective means of reducing discomfort
      during compression for a majority (73.5%) of our patients undergoing screening
      mammography. Image quality and the ability to detect all pertinent anatomy were
      maintained.

PMID- 15239796
TI  - Idiopathic benign breast calcification.
AB  - A 56-year-old woman who came in for screening mammography was found to have
      extensive unilateral calcification of her left breast which had developed since
      her previous screening mammogram. The calcification had a ductal and lobular
      appearance. Possible known etiologies are discussed, but these do not explain the
      appearance in this case, implying that the cause is idiopathic.

PMID- 15239795
TI  - Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic
      ACTH secretion.
AB  - Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH)
      secretion is rarely observed in breast carcinoma and only four cases have been
      previously published. We report here the case of a 50-year-old woman who
      presented with a history of diffuse bone pain associated with multiple hepatic,
      pulmonary, and bone metastases. A core needle biopsy specimen revealed an
      invasive ductal carcinoma in the right breast. The patient subsequently developed
      an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia
      and heart failure, despite treatment. At autopsy, immunohistochemical staining
      showed chromogranin A and ACTH positivity in the breast tumor and a lung
      metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was
      detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT
      PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH
      secretion where the presence of ACTH by immunohistochemistry and the expression
      of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with
      metastases. The clinical history and the pathologic findings are presented with
      the methods and results of the molecular analysis. This case illustrates an
      example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE)
      differentiation. This NE phenotype is directly related to the synthesis of ACTH
      by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may
      be produced not only by small cell carcinoma or endocrine tumors but also by
      breast cancer. No relationship has been established between NE features and
      prognostic factors or patient outcome for this peculiar type of breast carcinoma.
      The demonstration of mRNA POMC in breast carcinoma with NE features suggests a
      depression and/or an activation of the POMC gene linked to the NE
      differentiation.

PMID- 15239797
TI  - Diabetic fibrous mastopathy: dynamic contrast-enhanced magnetic resonance imaging
      findings.
AB  - Diabetic fibrous mastopathy (DFM) is an uncommon lesion that may clinically mimic
      breast carcinoma. Routine mammographic and ultrasonographic features of this
      disease also mimic the those of malignant disease, making an accurate
      preoperative diagnosis difficult. Dynamic contrast-enhanced magnetic resonance
      imaging (MRI), however, reveals a homogeneous low-enhancement with a gradual and
      progressive course without a washout. A corresponding time intensity curve is
      related to benign lesions of low vascularity, and by being a potential criterion
      for making a differentiation between DFM and malignant processes, spares patients
      from excisional biopsy.

PMID- 15239798
TI  - Mycobacterium fortuitum breast infection following nipple-piercing, mimicking
      carcinoma.
AB  - We reviewed a rare breast infection occurring 4 months after nipple piercing.
      Clinical examination suggested carcinoma. Mycobacterium fortuitum was eventually
      isolated after surgical biopsy and debridement. Antibiotic therapy was initiated
      intravenously using two drugs and oral therapy was continued for 6 months. A
      contralateral mycobacterial lesion emerged and was excised along with a residual
      fibrotic nodule at the original biopsy site. When adequate sampling of a complex
      and suspicious breast mass is benign and initial bacterial cultures are sterile,
      mycobacterial infection should be considered, particularly when there is a
      history of previous nipple piercing procedures.

PMID- 15239799
TI  - Osseous metaplasia of breast neuroma: diagnosis with stereotactic core biopsy.

PMID- 15239800
TI  - Gross pathologic and ultrasound appearances of a new breast biopsy marker.

PMID- 15239801
TI  - Myofibroblastoma of the breast.

PMID- 15239802
TI  - Sonographic and pathologic features of metastatic synovial sarcoma of the lung
      presenting as a breast neoplasm.

PMID- 15239803
TI  - Detection of minute breast cancers: a therapeutic challenge with a potential
      danger of overtreatment.

PMID- 15239804
TI  - False elevation of serum CA 15-3 levels in patients under follow-up for breast
      cancer.

PMID- 15239805
TI  - Malignant melanoma metastatic to the breast: an interdisciplinary challenge.

PMID- 15239807
TI  - The chordae tendineae of the heart in chicken.
AB  - In this study, the chordae tendineae of 10 adult chickens have been investigated
      by means of scanning electron microscopy (SEM). It has been observed that the
      diameter of the collagen fibrils on the left side of the heart was greater than
      those on the right side. The present study has determined that only perichordal
      and interchordal ligaments are present in the chicken. It was also observed that
      axial tendons were surrounded by perichordal membrane. Although no difference was
      evident among the apex of the chordae, differences were observed between the base
      and apex of the same chordae.

PMID- 15239808
TI  - Afferent and efferent connections of the nucleus geniculatus lateralis ventralis
      demonstrated by WGA-HRP in the chick.
AB  - Fibre connections of the chick nucleus geniculatus lateralis ventralis (GLv) were
      investigated using the axonal tracing method with wheat germ agglutinin
      conjugated to horseradish peroxidase (WGA-HRP). After an injection of WGA-HRP
      into the GLv, many labelled neurons were observed in layer i of the stratum
      griseum et fibrosum superficiale (SGFS) in the ipsilateral tectum opticum (TO)
      and in the nucleus lentiformis mesencephali (LM). In the TO-GLv projection, cells
      of origin were located in the deeper part of layer i of the TO and were
      topographically distributed along the direction from the rostrodorsal part to the
      caudoventral part of the TO relating to a rostrocaudal axis of the GLv. In the LM
      GLv connection, the dorsal and ventral parts of the LM connected reciprocally
      with the rostral and caudal halves of the GLv, respectively. In contrast, in the
      GLv efferent connection, labelled axon terminals spread widely in the ipsilateral
      area pretectalis without any clear topographical arrangement.

PMID- 15239809
TI  - Light and transmission electron microscopy of immature camelus dromedarius
      oocyte.
AB  - In order to provide a consistent system for laboratory production of embryos, the
      characteristics of immature camel oocyte must first be described. The objective
      of this study was to define ultrastructural features of immature camel oocyte.
      Ovaries were obtained from camels at a local abattoir, and then transported to
      the laboratory within 2 h. Camelus cumulus oocyte complexes (COCs) were aspirated
      from 2-6 mm follicles using a 22-gauge needle. Excellent and good quality COCs
      were selected and prepared for transmission electron microscopy study using a
      cavity slide. The fine structure of camel oocyte is morphologically similar to
      that of other mammalian oocytes. However, some minor differences exist between
      COC of camel and other mammalian species. Different size and shape of membrane
      bound vesicles, lipid droplet, mitochondria and cortical granules were
      distributed throughout the ooplasm. Discrete or in association with endoplasmic
      reticulum, Golgi complexes were observed in the periphery of the oocytes. The
      majority of the oocytes were in the germinal vesicle stage.

PMID- 15239810
TI  - [The blood vessels of the mesonephros of domestic cattle (Bos taurus), a
      corrosion cast study].
AB  - The blood vessels of the bovine mesonephros - a corrosion cast study Using
      scanning electron microscopy plastoid corrosion cast specimens of the mesonephros
      of 30-45-day-old bovine foetuses were investigated. The studies showed that the
      blood vessels of the mesonephros are organized in two separate networks similar
      to these of the teleosts and amphibians. The glomerula mesonephrica originate
      from the aorta implying that they belong to the high pressure system. The tubuli
      mesonephrici are surrounded by a filamentous independent capillary network which
      is shown for the first time in these studies. This capillary network originates
      from the caudal cardinal veins and represents a mesonephric portal system with a
      relatively low blood pressure. The blood from the two capillary networks diverts
      into terminal veins and into the subcardinal veins. The questions of
      haemodynamics in the mesonephros are discussed.

PMID- 15239811
TI  - Histochemical study on neurodegeneration in the olfactory bulb after transient
      forebrain ischaemia in the Mongolian gerbil.
AB  - In the present study, we investigated the ischaemia-related neurodegeneration in
      the main and accessory olfactory bulb (AOB) after 5 min transient forebrain
      ischaemia in the Mongolian gerbil using the acid fuchsin staining method. Between
      5 and 15 days after ischaemia, acid fuchsin positive cells markedly increased in
      the external plexiform layer (EPL), mitral cell layer (ML) and glomerular layer
      (GL) of the main olfactory bulb (MOB), and in the mixed cell layer (MCL) and GL
      of the AOB. By 30 days after ischaemia reperfusion, acid fuchsin positive neurons
      were shrunken and showed low acidophilia in somata. Many necrotic vacuoles were
      found in the EPL and GL of the MOB 30 days after ischaemia. At this time,
      necrotic vacuoles were very few in the AOB. Therefore, our results suggest that
      the GL and EPL of the MOB are vulnerable to ischaemic damage at a later time
      after ischaemic insult, and that the AOB is more resistant to ischaemic damage as
      compared with the MOB.

PMID- 15239812
TI  - Immunohistochemical study on the endocrine cells in gut of the stomachless
      teleost, Zacco platypus (Cyprinidae).
AB  - The regional distribution and relative frequency of neurohormonal peptides
      producing cells were demonstrated in the gut of the stomachless teleost, Zacco
      platypus (Temminck et Schegel), using 10 types of specific antisera raised
      against mammalian regulatory peptides. The gut of Z. platypus was divided into
      five portions from proximal to distal (segment I-V). Most of immunoreactive cells
      in the epithelial lining portion, between epithelial cells, were generally
      spherical or spindle shape having long cytoplasmic process that was reached via
      the lumen while cells round in shape were found in the basal portions of
      epithelial lining occasionally. Serotonin-, somatostatin-, glucagon-,
      cholecystokinin (CCK)-8 and pancreatic polypeptide (PP)-immunoreactive cells were
      observed in this study. However, no chromogranin A-, secretin-, vasoactive
      intestinal peptide (VIP)-, substance P- and bombesin-immunoreactive cells were
      found. Serotonin-immunoreactive cells were demonstrated throughout the entire gut
      tract and occurred more frequently than other cells. Somatostatin-immunoreactive
      cells were restricted to proximal segments of the gut (segment I-III) with rare
      frequencies, and glucagon-immunoreactive cells were demonstrated in the proximal
      segments of the gut (segment I, II) with moderate to few occurrences. CCK-8
      immunoreactive cells were found throughout the whole intestinal tract except for
      most proximal segment (segment I) with moderate to few frequencies and PP
      immunoreactive cells were demonstrated in the proximal to middle segments,
      segment I-III, with a few, rare and rare frequencies, respectively.

PMID- 15239814
TI  - Endocrine-paracrine cells of the male urogenital apparatus: a comparative
      histochemical and immunohistochemical study in some domestic ungulates.
AB  - Specimens of testis, excurrent duct including the male accessory glands and
      urethra, were studied in boars, bulls, horses and donkeys, in order to localize
      endocrine/paracrine cells. Silver impregnation methods were used to test the
      argentaffinity and/or argyrophilia of cells. Immunoreactivities to chromogranin
      A, 5-hydroxytryptamine, somatostatin, [met]- and [leu]- enkephalins, gastrin
      releasing peptide, calcitonin gene-related peptide, neuropeptide Y, substance P,
      vasoactive intestinal peptide, beta-endorphin antisera were tested by a
      streptavidin-biotin method. In the testis, epididymis, ductus deferens and
      vesicular gland no endocrine cells were found in any of the animals studied.
      Chromogranin-A, serotonin, somatostatin and enkephalins were present in
      endocrine/paracrine cells in the surface or glandular epithelia, whereas all
      other antisera gave negative results. In the prostatic complex and the urethral
      epithelium, the most consistent number of endocrine cells was serotonin
      immunoreactive. Few cells were also argentaffin and a very limited number of them
      showed argyrophily and chromogranin-A immunoreactivity. Somatostatin-and
      enkephalin-immunoreactive cells were rare in the bull and boar, absent in
      stallions. This comparative study carried out on different species of domestic
      ungulates has shown deeply different immunophenotypes, even comparing species
      that are in a very close zoological relationship with one another, such as the
      horse and the donkey.

PMID- 15239813
TI  - Chronological alterations of P2X3 receptor expression in the trigeminal ganglion
      after ischaemic insult in the Mongolian gerbil.
AB  - P2X receptors play a role in the transduction of sensory signals like pain. Few
      studies have been undertaken on altered P2X(3) receptor (P2X3) expression in
      sensory neurones after peripheral nerve injury. In the present study, we
      investigated chronological alterations in P2X3 immunoreactivity and its protein
      content in the trigeminal ganglion after ischaemic insult in the Mongolian
      gerbil. In the sham-operated group, P2X3-immunoreactive neurones were found
      abundantly in small- and medium-sized neurones. From 1 day after ischaemic
      insult, the number of P2X3-immunoreactive neurones decreased significantly. At 5
      days after ischaemic insult, P2X3 immunoreactivity was observed in few neurones,
      but its immunoreactivity was weak. However, the number of cresyl violet-positive
      neurones was unchanged throughout this period in all groups. These results
      suggest that transient trigeminal ganglion ischaemia may provoke a decrease of
      P2X3 expression and its protein content, and that this down-regulation of P2X3
      may be related to the altered pain and thermal sensation without being associated
      with a transient ischaemic insult.

PMID- 15239815
TI  - The venous drainage of the heart in porcupines (Hystrix cristata).
AB  - The venous drainage of the heart in porcupines (Hystrix cristata) was
      investigated. Each of the five adult porcupines (three males, two females) was
      injected with a coloured latex mixture via the V. cava caudalis for the
      demonstration of the cardiac veins. The dissection of the specimens revealed that
      the venous drainage of the heart in porcupines was made by the V. cordis magna,
      V. distalis ventriculi sinistri, V. proximalis ventriculi sinistri, V. cordis
      caudalis (the left marginal vein), V. cordis media and Vv. cordis dextrae. The
      cardiac veins were observed in a subepicardial course on the heart except for the
      R. interventricularis paraconalis. The R. interventricularis paraconalis showed
      an intramyocardial course until the middle of the sulcus interventricularis
      paraconalis, and a subepicardial course after this point. The V. cordis magna and
      V. distalis ventriculi sinistri opened to the sinus coronarius. The V. cordis
      caudalis and the V. cordis media drained into the V. cava caudalis. The venous
      drainage of the conus arteriosus was made by the left V. coni arteriosi opening
      to the R. interventricularis paraconalis, and by the right V. coni arteriosi
      which continued to the Vv. cordis dextrae.

PMID- 15239816
TI  - Histochemical skeletal muscle fibre types in the sheep.
AB  - In this study, the differentiation of adult and postnatal muscle fibres in sheep
      longissimus thoracis muscle has been characterized. By using a variety of
      histochemical methods, we have investigated the m-ATPase and metabolic activities
      of skeletal muscle fibres in adult sheep and lambs aged between 1 day and 3
      months. Types I, IIA, IIB and IIC fibres were identified. The results showed that
      the interpretation of the fibre type composition depends on the methods used. The
      findings also revealed that the fibre types IIA and IIB can be separated
      histochemically in sheep by using the correct m-ATPase technique, even at early
      stages of postnatal development, and that the origin of the four different fibres
      of the adult can be traced back to early postnatal stages.

PMID- 15239817
TI  - A morphometric investigation on breed-specific features affecting sagittal
      rotational and lateral bending mobility in the canine cervical spine (c3-c7).
AB  - Vertebral and inter-vertebral parameters obtained in large breeds (n = 74), small
      breeds (n = 35), and Dachshunds (n = 30) were compared to reveal potential
      differences in the range of motion of the cervical spine between these three
      groups of breeds. Body size normalized dimensions of vertebral and inter
      vertebral parameters and correlations between these indicate large canine breeds
      to have a tendency towards higher range of motion in sagittal rotation and
      lateral bending compared with Dachshunds and small breeds. Higher mobility in
      large breeds is based on significantly (P < 0.05) lower vertebral endplate
      heights and widths, shorter vertebral bodies and longer inter-vertebral discs,
      wider but shorter cranial and caudal articular surfaces, larger differences in
      width between caudal and cranial joining facets (compared with Dachshunds from
      C3/4 to C6/7, compared with small breeds from C4/5 to C5/6), and larger
      differences in length between caudal and cranial joining facets. Large
      differences in width between caudal and cranial joining facets were associated
      with small distances between the most medial (C3/4 to C6/7) and lateral (C3/4 to
      C5/6) aspects of the articular surfaces as well as with small differences in
      length between caudal and cranial joining facets (C3/4 to C5/6). This suggests
      that from C3/4 to C5/6 a higher range of motion in lateral bending is coupled to
      a lower range of motion in sagittal rotation. The present findings contribute
      also to explain the higher incidence of degenerative lesions of the cervical
      spine in large dogs.

PMID- 15239819
TI  - After 'completion': the changing face of human chromosomes 21 and 22.
AB  - In the four years since the publication of the first two 'complete' human
      chromosome sequences the type of research being done on each has shifted subtly,
      reflecting the impact of genomic data on biological science in general. There is
      now considerably more gene-expression evidence to support predicted genes, and
      the annotation of functions for previously unknown genes, including those
      implicated in disease, is gradually improving.

PMID- 15239820
TI  - The uses of genome-wide yeast mutant collections.
AB  - We assess five years of usage of the major genome-wide collections of mutants
      from Saccharomyces cerevisiae: single deletion mutants, double mutants conferring
      'synthetic' lethality and the 'TRIPLES' collection of mutants obtained by random
      transposon insertion. Over 100 experimental conditions have been tested and more
      than 5,000 novel phenotypic traits have been assigned to yeast genes using these
      collections.

PMID- 15239821
TI  - Candida albicans genome sequence: a platform for genomics in the absence of
      genetics.
AB  - Publication of the complete diploid genome sequence of the yeast Candida albicans
      will accelerate research into the pathogenesis of Candida infections. Comparative
      genomic analysis highlights genes that may contribute to C. albicans survival and
      its fitness as a human commensal and pathogen.

PMID- 15239822
TI  - Analysis of alternative splicing with microarrays: successes and challenges.
AB  - Recently, DNA microarrays have emerged as potentially powerful tools for
      analyzing alternative splicing. We briefly review the latest results in this
      field and highlight the current challenges that they have revealed.

PMID- 15239823
TI  - Cross-species comparison of genome-wide expression patterns.
AB  - The rapid accumulation of microarray data from multiple species provides
      unprecedented opportunities to study the evolution of biological systems. Recent
      studies have used cross-species comparisons of expression profiles to annotate
      gene functions, to draw evolutionary inferences concerning specific biological
      processes and to study the global properties of expression networks.

PMID- 15239824
TI  - Unfashionable crop species flourish in the 21st century.
AB  - Genome-level studies are contributing to a major renaissance in crop science. In
      wheat, there are now more than 500,000 expressed sequence tags, and these are
      being used in conjunction with specially designed deletion stocks to unravel
      patterns of genome evolution, recombination and polyploid genome behavior.

PMID- 15239825
TI  - The Frizzled family: receptors for multiple signal transduction pathways.
AB  - Frizzled genes encode integral membrane proteins that function in multiple signal
      transduction pathways. They have been identified in diverse animals, from sponges
      to humans. The family is defined by conserved structural features, including
      seven hydrophobic domains and a cysteine-rich ligand-binding domain. Frizzled
      proteins are receptors for secreted Wnt proteins, as well as other ligands, and
      also play a critical role in the regulation of cell polarity. Frizzled genes are
      essential for embryonic development, tissue and cell polarity, formation of
      neural synapses, and the regulation of proliferation, and many other processes in
      developing and adult organisms; mutations in human frizzled-4 have been linked to
      familial exudative vitreoretinopathy. It is not yet clear how Frizzleds couple to
      downstream effectors, and this is a focus of intense study.

PMID- 15239826
TI  - Integrative functional genomics.

PMID- 15239827
TI  - Cancer, oncogenes and signal transduction.

PMID- 15239828
TI  - Developmental biology reaches new lineages.

PMID- 15239829
TI  - Tissue-specific spatial organization of genomes.
AB  - BACKGROUND: Genomes are organized in vivo in the form of chromosomes. Each
      chromosome occupies a distinct nuclear subvolume in the form of a chromosome
      territory. The spatial positioning of chromosomes within the interphase nucleus
      is often nonrandom. It is unclear whether the nonrandom spatial arrangement of
      chromosomes is conserved among tissues or whether spatial genome organization is
      tissue-specific. RESULTS: Using two-dimensional and three-dimensional
      fluorescence in situ hybridization we have carried out a systematic analysis of
      the spatial positioning of a subset of mouse chromosomes in several tissues. We
      show that chromosomes exhibit tissue-specific organization. Chromosomes are
      distributed tissue-specifically with respect to their position relative to the
      center of the nucleus and also relative to each other. Subsets of chromosomes
      form distinct types of spatial clusters in different tissues and the relative
      distance between chromosome pairs varies among tissues. Consistent with the
      notion that nonrandom spatial proximity is functionally relevant in determining
      the outcome of chromosome translocation events, we find a correlation between
      tissue-specific spatial proximity and tissue-specific translocation prevalence.
      CONCLUSIONS: Our results demonstrate that the spatial organization of genomes is
      tissue-specific and point to a role for tissue-specific spatial genome
      organization in the formation of recurrent chromosome arrangements among tissues.

PMID- 15239830
TI  - Recombination and base composition: the case of the highly self-fertilizing plant
      Arabidopsis thaliana.
AB  - BACKGROUND: Rates of recombination can vary among genomic regions in eukaryotes,
      and this is believed to have major effects on their genome organization in terms
      of base composition, DNA repeat density, intron size, evolutionary rates and gene
      order. In highly self-fertilizing species such as Arabidopsis thaliana, however,
      heterozygosity is expected to be strongly reduced and recombination will be much
      less effective, so that its influence on genome organization should be greatly
      reduced. RESULTS: Here we investigated theoretically the joint effects of
      recombination and self-fertilization on base composition, and tested the
      predictions with genomic data from the complete A. thaliana genome. We show that,
      in this species, both codon-usage bias and GC content do not correlate with the
      local rates of crossing over, in agreement with our theoretical results.
      CONCLUSIONS: We conclude that levels of inbreeding modulate the effect of
      recombination on base composition, and possibly other genomic features (for
      example, transposable element dynamics). We argue that inbreeding should be
      considered when interpreting patterns of molecular evolution.

PMID- 15239831
TI  - Identification of conserved gene structures and carboxy-terminal motifs in the
      Myb gene family of Arabidopsis and Oryza sativa L. ssp. indica.
AB  - BACKGROUND: Myb proteins contain a conserved DNA-binding domain composed of one
      to four repeat motifs (referred to as R0R1R2R3); each repeat is approximately 50
      amino acids in length, with regularly spaced tryptophan residues. Although the
      Myb proteins comprise one of the largest families of transcription factors in
      plants, little is known about the functions of most Myb genes. Here we use
      computational techniques to classify Myb genes on the basis of sequence
      similarity and gene structure, and to identify possible functional relationships
      among subgroups of Myb genes from Arabidopsis and rice (Oryza sativa L. ssp.
      indica). RESULTS: This study analyzed 130 Myb genes from Arabidopsis and 85 from
      rice. The collected Myb proteins were clustered into subgroups based on sequence
      similarity and phylogeny. Interestingly, the exon-intron structure differed
      between subgroups, but was conserved in the same subgroup. Moreover, the Myb
      domains contained a significant excess of phase 1 and 2 introns, as well as an
      excess of nonsymmetric exons. Conserved motifs were detected in carboxy-terminal
      coding regions of Myb genes within subgroups. In contrast, no common regulatory
      motifs were identified in the noncoding regions. Additionally, some Myb genes
      with similar functions were clustered in the same subgroups. CONCLUSIONS: The
      distribution of introns in the phylogenetic tree suggests that Myb domains
      originally were compact in size; introns were inserted and the splicing sites
      conserved during evolution. Conserved motifs identified in the carboxy-terminal
      regions are specific for Myb genes, and the identified Myb gene subgroups may
      reflect functional conservation.

PMID- 15239832
TI  - Evolutionary conservation and selection of human disease gene orthologs in the
      rat and mouse genomes.
AB  - BACKGROUND: Model organisms have contributed substantially to our understanding
      of the etiology of human disease as well as having assisted with the development
      of new treatment modalities. The availability of the human, mouse and, most
      recently, the rat genome sequences now permit the comprehensive investigation of
      the rodent orthologs of genes associated with human disease. Here, we investigate
      whether human disease genes differ significantly from their rodent orthologs with
      respect to their overall levels of conservation and their rates of evolutionary
      change. RESULTS: Human disease genes are unevenly distributed among human
      chromosomes and are highly represented (99.5%) among human-rodent ortholog sets.
      Differences are revealed in evolutionary conservation and selection between
      different categories of human disease genes. Although selection appears not to
      have greatly discriminated between disease and non-disease genes, synonymous
      substitution rates are significantly higher for disease genes. In neurological
      and malformation syndrome disease systems, associated genes have evolved slowly
      whereas genes of the immune, hematological and pulmonary disease systems have
      changed more rapidly. Amino-acid substitutions associated with human inherited
      disease occur at sites that are more highly conserved than the average;
      nevertheless, 15 substituting amino acids associated with human disease were
      identified as wild-type amino acids in the rat. Rodent orthologs of human
      trinucleotide repeat-expansion disease genes were found to contain substantially
      fewer of such repeats. Six human genes that share the same characteristics as
      triplet repeat-expansion disease-associated genes were identified; although four
      of these genes are expressed in the brain, none is currently known to be
      associated with disease. CONCLUSIONS: Most human disease genes have been retained
      in rodent genomes. Synonymous nucleotide substitutions occur at a higher rate in
      disease genes, a finding that may reflect increased mutation rates in the
      chromosomal regions in which disease genes are found. Rodent orthologs associated
      with neurological function exhibit the greatest evolutionary conservation; this
      suggests that rodent models of human neurological disease are likely to most
      faithfully represent human disease processes. However, with regard to
      neurological triplet repeat expansion-associated human disease genes, the
      contraction, relative to human, of rodent trinucleotide repeats suggests that
      rodent loci may not achieve a 'critical repeat threshold' necessary to undergo
      spontaneous pathological repeat expansions. The identification of six genes in
      this study that have multiple characteristics associated with repeat expansion
      disease genes raises the possibility that not all human loci capable of
      facilitating neurological disease by repeat expansion have as yet been
      identified.

PMID- 15239833
TI  - From co-expression to co-regulation: how many microarray experiments do we need?
AB  - BACKGROUND: Cluster analysis is often used to infer regulatory modules or
      biological function by associating unknown genes with other genes that have
      similar expression patterns and known regulatory elements or functions. However,
      clustering results may not have any biological relevance. RESULTS: We applied
      various clustering algorithms to microarray datasets with different sizes, and we
      evaluated the clustering results by determining the fraction of gene pairs from
      the same clusters that share at least one known common transcription factor. We
      used both yeast transcription factor databases (SCPD, YPD) and chromatin
      immunoprecipitation (ChIP) data to evaluate our clustering results. We showed
      that the ability to identify co-regulated genes from clustering results is
      strongly dependent on the number of microarray experiments used in cluster
      analysis and the accuracy of these associations plateaus at between 50 and 100
      experiments on yeast data. Moreover, the model-based clustering algorithm MCLUST
      consistently outperforms more traditional methods in accurately assigning co
      regulated genes to the same clusters on standardized data. CONCLUSIONS: Our
      results are consistent with respect to independent evaluation criteria that
      strengthen our confidence in our results. However, when one compares ChIP data to
      YPD, the false-negative rate is approximately 80% using the recommended p-value
      of 0.001. In addition, we showed that even with large numbers of experiments, the
      false-positive rate may exceed the true-positive rate. In particular, even when
      all experiments are included, the best results produce clusters with only a 28%
      true-positive rate using known gene transcription factor interactions.

PMID- 15239834
TI  - Systematic quantification of gene interactions by phenotypic array analysis.
AB  - A phenotypic array method, developed for quantifying cell growth, was applied to
      the haploid and homozygous diploid yeast deletion strain sets. A growth index was
      developed to screen for non-additive interacting effects between gene deletion
      and induced perturbations. From a genome screen for hydroxyurea (HU) chemical
      genetic interactions, 298 haploid deletion strains were selected for further
      analysis. The strength of interactions was quantified using a wide range of HU
      concentrations affecting reference strain growth. The selectivity of interaction
      was determined by comparison with drugs targeting other cellular processes. Bio
      modules were defined as gene clusters with shared strength and selectivity of
      interaction profiles. The functions and connectivity of modules involved in
      processes such as DNA repair, protein secretion and metabolic control were
      inferred from their respective gene composition. The work provides an example of,
      and a general experimental framework for, quantitative analysis of gene
      interaction networks that buffer cell growth.

PMID- 15239835
TI  - Detecting DNA regulatory motifs by incorporating positional trends in information
      content.
AB  - On the basis of the observation that conserved positions in transcription factor
      binding sites are often clustered together, we propose a simple extension to the
      model-based motif discovery methods. We assign position-specific prior
      distributions to the frequency parameters of the model, penalizing deviations
      from a specified conservation profile. Examples with both simulated and real data
      show that this extension helps discover motifs as the data become noisier or when
      there is a competing false motif.

PMID- 15239836
TI  - Clustering analysis of SAGE data using a Poisson approach.
AB  - Serial analysis of gene expression (SAGE) data have been poorly exploited by
      clustering analysis owing to the lack of appropriate statistical methods that
      consider their specific properties. We modeled SAGE data by Poisson statistics
      and developed two Poisson-based distances. Their application to simulated and
      experimental mouse retina data show that the Poisson-based distances are more
      appropriate and reliable for analyzing SAGE data compared to other commonly used
      distances or similarity measures such as Pearson correlation or Euclidean
      distance.

PMID- 15239837
TI  - Human chorionic gonadotropin administration is associated with high pregnancy
      rates during ovarian stimulation and timed intercourse or intrauterine
      insemination.
AB  - BACKGROUND: There are different factors that influence treatment outcome after
      ovarian stimulation and timed-intercourse or intrauterine insemination (IUI).
      After patient age, it has been suggested that timing of insemination in relation
      to ovulation is probably the most important variable affecting the success of
      treatment. The objective of this study is to study the value of human chorionic
      gonadotropin (hCG) administration and occurrence of luteinizing hormone (LH)
      surge in timing insemination on the treatment outcome after follicular monitoring
      with timed-intercourse or intrauterine insemination, with or without ovarian
      stimulation. METHODS: Retrospective analysis of 2000 consecutive completed
      treatment cycles (637 timed-intercourse and 1363 intrauterine insemination
      cycles). Stimulation protocols included clomiphene alone or with FSH injection,
      letrozole (an aromatase inhibitor) alone or with FSH, and FSH alone. LH-surge was
      defined as an increase in LH level > or =200% over mean of preceding two days.
      When given, hCG was administered at a dose of 10,000 IU. The main outcome was
      clinical pregnancy rate per cycle. RESULTS: Higher pregnancy rates occurred in
      cycles in which hCG was given. Occurrence of an LH-surge was associated with a
      higher pregnancy rate with clomiphene treatment, but a lower pregnancy rate with
      FSH treatment. CONCLUSIONS: hCG administration is associated with a favorable
      outcome during ovarian stimulation. Awaiting occurrence of LH-surge is associated
      with a better outcome with CC but not with FSH treatment.

PMID- 15239839
TI  - The use of a spatial information system in the management of HIV/AIDS in South
      Africa.
AB  - BACKGROUND: South Africa is experiencing an HIV/AIDS pandemic of shattering
      dimensions. The availability and provision of antiretroviral (ARV) drugs could
      bring relief to the situation, but the treatment is unfortunately complex with
      each patient being assigned a different antiretroviral therapy varying in diet
      medication regiment. The context of South Africa, its variety of urban and rural
      settings adds to the challenge of administering and monitoring the HIV+ person
      throughout the treatment, which will last for the rest of their lives. The lack
      of physical infrastructure, reliable statistics and adequate resources hinder the
      efficient management of HIV/AIDS. RESULTS: The collection of reliable data will
      be a first step to assess the status of HIV/AIDS in communities. A number of
      hospitals have started this process using the conventional approach to collect
      information about their patients using a paper-based system. Since time is of
      essence in the fight against the pandemic, data exchange between various
      hospitals, municipalities and decision-making bodies is becoming more and more
      important. The logical response to such a need is a computerised system, which
      will collect and administer HIV/AIDS related information within the local context
      and allow a monitored access to the data from a number of stakeholders.
      CONCLUSIONS: The purpose of this study was to design and develop an HIV/AIDS
      database, which is embedded in a Spatial Information Management System. The pilot
      study area is the Gugulethu township in Cape Town where more than 27% of the 325
      000 residents are HIV+. It is shown that the implementation of the HIV/AIDS
      database and the Spatial Information Management System can play a critical role
      in determining where and when to intervene, improving the quality of care for
      HIV+ patients, increasing accessibility of service and delivering a cost
      effective mode of information.

PMID- 15239838
TI  - Microarray profiling of progesterone-regulated endometrial genes during the
      rhesus monkey secretory phase.
AB  - BACKGROUND: In the endometrium the steroid hormone progesterone (P), acting
      through its nuclear receptors, regulates the expression of specific target genes
      and gene networks required for endometrial maturation. Proper endometrial
      maturation is considered a requirement for embryo implantation. Endometrial
      receptivity is a complex process that is spatially and temporally restricted and
      the identity of genes that regulate receptivity has been pursued by a number of
      investigators. METHODS: In this study we have used high density oligonucleotide
      microarrays to screen for changes in mRNA transcript levels between normal
      proliferative and adequate secretory phases in Rhesus monkey artificial menstrual
      cycles. Biotinylated cRNA was prepared from day 13 and days 21-23 of the
      reproductive cycle and transcript levels were compared by hybridization to
      Affymetrix HG-U95A arrays. RESULTS: Of approximately 12,000 genes profiled, we
      identified 108 genes that were significantly regulated during the shift from a
      proliferative to an adequate secretory endometrium. Of these genes, 39 were up
      regulated at days 21-23 versus day 13, and 69 were down-regulated. Genes up
      regulated in P-dominant tissue included: secretoglobin (uteroglobin), histone 2A,
      polo-like kinase (PLK), spermidine/spermine acetyltransferase 2 (SAT2), secretory
      leukocyte protease inhibitor (SLPI) and metallothionein 1G (MT1G), all of which
      have been previously documented as elevated in the Rhesus monkey or human
      endometrium during the secretory phase. Genes down-regulated included:
      transforming growth factor beta-induced (TGFBI or BIGH3), matrix
      metalloproteinase 11 (stromelysin 3), proenkephalin (PENK), cysteine/glycine-rich
      protein 2 (CSRP2), collagen type VII alpha 1 (COL7A1), secreted frizzled-related
      protein 4 (SFRP4), progesterone receptor membrane component 1 (PGRMC1), chemokine
      (C-X-C) ligand 12 (CXCL12) and biglycan (BGN). In addition, many novel/unknown
      genes were also identified. Validation of array data was performed by semi
      quantitative RT-PCR of two selected up-regulated genes using temporal (cycle day
      specific) endometrial cDNA populations. This approach confirmed up-regulation of
      WAP four-disulfide core domain 2 (WFDC2) and SLPI during the expected window of
      receptivity. CONCLUSION: The identification of P-regulated genes and gene
      pathways in the primate endometrium is expected to be an important first step in
      elucidating the cellular processes necessary for the development of a receptive
      environment for implantation.

PMID- 15239841
TI  - Assessment of the role of transcript for GATA-4 as a marker of unfavorable
      outcome in human adrenocortical neoplasms.
AB  - BACKGROUND: Malignant neoplasia of the adrenal cortex is usually associated with
      very poor prognosis. When adrenocortical neoplasms are diagnosed in the early
      stages, distinction between carcinoma and adenoma can be very difficult to
      accomplish, since there is yet no reliable marker to predict tumor recurrence or
      dissemination. GATA transcription factors play an essential role in the
      developmental control of cell fate, cell proliferation and differentiation, organ
      morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex
      expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal
      of the present study was to assess whether this reciprocal change in the
      expression of GATA factors might be relevant for predicting the prognosis of
      human adrenocortical neoplasms. Since human adrenal cortices express luteinizing
      hormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4
      in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor.
      METHODS: We conducted a study on 13 non-metastasizing (NM) and 10
      metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and
      pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR)
      in normal and tumoral human adrenal cortices was analysed using reverse
      transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot
      hybridization. RESULTS: Messenger RNA for GATA-6 was detected in normal adrenal
      tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was
      detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10
      MR tumors, with larger amounts of mRNA found among those presenting aggressive
      clinical behavior. Transcripts for LH receptor were observed both in normal
      tissue and neoplasms. A more intense LHR transcript accumulation was observed on
      those tumors with better clinical outcome. CONCLUSION: Our data suggest that the
      expression of GATA-6 in human adrenal cortex is not affected by tumorigenesis.
      GATA-4 expression is more abundant in MR tumors, while NM tumors express more
      intensely LHR. Further studies with larger cohorts are needed to test whether
      relative expression levels of LHR or GATA-4 might be used as prognosis
      predictors.

PMID- 15239842
TI  - Quantitative promoter analysis in Physcomitrella patens: a set of plant vectors
      activating gene expression within three orders of magnitude.
AB  - BACKGROUND: In addition to studies of plant gene function and developmental
      analyses, plant biotechnological use is largely dependent upon transgenic
      technologies. The moss Physcomitrella patens has become an exciting model system
      for studying plant molecular processes due to an exceptionally high rate of
      nuclear gene targeting by homologous recombination compared with other plants.
      However, its use in transgenic approaches requires expression vectors that
      incorporate sufficiently strong promoters. To satisfy this requirement, a set of
      plant expression vectors was constructed and equipped with either heterologous or
      endogenous promoters. RESULTS: Promoter activity was quantified using the dual
      luciferase reporter assay system. The eight different heterologous promoter
      constructs tested exhibited expression levels spanning three orders of magnitude.
      Of these, the complete rice actin1 gene promoter showed the highest activity in
      Physcomitrella, followed by a truncated version of this promoter and three
      different versions of the cauliflower mosaic virus 35S promoter. In contrast, the
      Agrobacterium tumefaciens nopaline synthase promoter induced transcription rather
      weakly. Constructs including promoters commonly used in mammalian expression
      systems also proved to be functional in Physcomitrella. In addition, the 5' 
      regions of two Physcomitrella glycosyltransferases (i.e. alpha1,3
      fucosyltransferase and beta1,2-xylosyltransferase) were identified and
      functionally characterised in comparison to the heterologous promoters.
      Furthermore, motifs responsible for enhancement of translation efficiency - such
      as the TMV omega element and a modified sequence directly prior the start codon -
      were tested in this model. CONCLUSION: We developed a vector set that enables
      gene expression studies, both in lower and higher land plants, thus providing
      valuable tools applicable in both basic and applied molecular research.

PMID- 15239843
TI  - Magnetic resonance imaging of anterior cruciate ligament rupture.
AB  - BACKGROUND: Magnetic resonance (MR) imaging is a useful diagnostic tool for the
      assessment of knee joint injury. Anterior cruciate ligament repair is a commonly
      performed orthopaedic procedure. This paper examines the concordance between MR
      imaging and arthroscopic findings. METHODS: Between February, 1996 and February,
      1998, 48 patients who underwent magnetic resonance (MR) imaging of the knee were
      reported to have complete tears of the anterior cruciate ligament (ACL). Of the
      48 patients, 36 were male, and 12 female. The average age was 27 years (range: 15
      to 45). Operative reconstruction using a patellar bone-tendon-bone autograft was
      arranged for each patient, and an arthroscopic examination was performed to
      confirm the diagnosis immediately prior to reconstructive surgery. RESULTS: In 16
      of the 48 patients, reconstructive surgery was cancelled when incomplete lesions
      were noted during arthroscopy, making reconstructive surgery unnecessary. The
      remaining 32 patients were found to have complete tears of the ACL, and therefore
      underwent reconstructive surgery. Using arthroscopy as an independent, reliable
      reference standard for ACL tear diagnosis, the reliability of MR imaging was
      evaluated. The true positive rate for complete ACL tear diagnosis with MR imaging
      was 67%, making the possibility of a false-positive report of "complete ACL tear"
      inevitable with MR imaging. CONCLUSIONS: Since conservative treatment is
      sufficient for incomplete ACL tears, the decision to undertake ACL reconstruction
      should not be based on MR findings alone.

PMID- 15239844
TI  - SPOC: a widely distributed domain associated with cancer, apoptosis and
      transcription.
AB  - BACKGROUND: The Split ends (Spen) family are large proteins characterised by N
      terminal RNA recognition motifs (RRMs) and a conserved SPOC (Spen paralog and
      ortholog C-terminal) domain. The aim of this study is to characterize the family
      at the sequence level. RESULTS: We describe undetected members of the Spen family
      in other lineages (Plasmodium and Plants) and localise SPOC in a new domain
      context, in a family that is common to all eukaryotes using profile-based
      sequence searches and structural prediction methods. CONCLUSIONS: The widely
      distributed DIO (Death inducer-obliterator) family is related to cancer and
      apoptosis and offers new clues about SPOC domain functionality.

PMID- 15239845
TI  - Global features of sequences of bacterial chromosomes, plasmids and phages
      revealed by analysis of oligonucleotide usage patterns.
AB  - BACKGROUND: Oligonucleotide frequencies were shown to be conserved signatures for
      bacterial genomes, however, the underlying constraints have yet not been resolved
      in detail. In this paper we analyzed oligonucleotide usage (OU) biases in a
      comprehensive collection of 155 completely sequenced bacterial chromosomes, 316
      plasmids and 104 phages. RESULTS: Two global features were analyzed: pattern skew
      (PS) and variance of OU deviations normalized by mononucleotide content of the
      sequence (OUV). OUV reflects the strength of OU biases and taxonomic signals. PS
      denotes asymmetry of OU in direct and reverse DNA strands. A trend towards
      minimal PS was observed for almost all complete sequences of bacterial
      chromosomes and plasmids, however, PS was substantially higher in separate
      genomic loci and several types of plasmids and phages characterized by long
      stretches of non-coding DNA and/or asymmetric gene distribution on the two DNA
      strands. Five of the 155 bacterial chromosomes have anomalously high PS, of which
      the chromosomes of Xylella fastidiosa 9a5c and Prochlorococcus marinus MIT9313
      exhibit extreme PS values suggesting an intermediate unstable state of these two
      genomes. CONCLUSIONS: Strand symmetry as indicated by minimal PS is a universally
      conserved feature of complete bacterial genomes that results from the matching
      mutual compensation of local OU biases on both replichors while OUV is more a
      taxon specific feature. Local events such as inversions or the incorporation of
      genome islands are balanced by global changes in genome organization to minimize
      PS that may represent one of the leading evolutionary forces driving bacterial
      genome diversification.

PMID- 15239846
TI  - Balancing commercial and public interests.
AB  - Alarge number of randomized clinical trials with important health outcomes are
      completed each year. Those with favorable findings are typically reported and
      published rapidly, while the publication of those with unfavorable results is
      often delayed or given a positive "spin." This observation applies primarily to
      industry-sponsored trials. Our objectives are to discuss the responsibility of
      pharmaceutical firms to the public with respect to timely, complete, and unbiased
      information from all randomized clinical trials and to propose solutions for
      improvements. We believe that in addition to financial obligations to their
      shareholders, pharmaceutical companies have social responsibilities to the public
      and to health care providers. However, private markets do not reward or compel
      optimal disclosure of drug safety or inferiority information on a voluntary
      basis.A problem which has not previously been identified relates to non
      comparability of drugs. A case report from the Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public
      interests may be violated due to failure to inform about drug inferiority. The
      current system for dissemination of relevant medical information could be
      improved if all involved parties collaborated fully. However, full disclosure of
      trial results is unlikely when research results are unfavorable to the firm. We
      conclude that expanded government regulations will be required for a satisfactory
      solution to the problem.

PMID- 15239847
TI  - Monitoring sulfur mustard exposure by gas chromatography-mass spectrometry
      analysis of thiodiglycol cleaved from blood proteins.
AB  - A gas chromatography-mass spectrometry method for determining exposure to the
      chemical warfare agent 2,2'-dichlorodiethyl sulfide (sulfur mustard; HD) has been
      developed. The technique is based upon quantitating thiodiglycol (TDG) released
      from blood protein adducts that are formed upon exposure to HD. Protein was
      precipitated from plasma, whole blood, or packed red blood cells (RBCs) and then
      treated with sodium hydroxide to liberate protein-bound TDG. The TDG was
      derivatized with pentafluorobenzoyl chloride that enabled sensitive detection by
      negative-ion chemical ionization. Octadeuterothiodiglycol was used as an internal
      standard. Exposure of human plasma to HD (25 nM to 400 nM) resulted in a linear
      relationship (r2 = 0.9995) between HD concentration and released TDG levels with
      means ranging from 2.0 to 38 pg/mg protein. The coefficients of variation
      expressed as a percentage for the data points ranged from 2 to 11.5%. The
      application of this procedure was demonstrated in two HD animal exposure models.
      African green monkeys (Chlorocebus aethiops) were exposed intravenously to 1
      mg/kg HD, and TDG levels in blood samples were analyzed out to 45 days post
      exposure. Mean TDG levels were determined to be 220 pg/mg protein on day 1 and
      declined to 10 pg/mg protein on day 45. Yorkshire cross pigs (Sus scrofa) were
      cutaneously exposed to neat liquid HD, and TDG levels in plasma were determined
      out to 21 days following exposure. Mean TDG levels were found to be 60 pg/mg
      protein on day one and decreased to an average of 4 pg/mg protein on day 21. The
      data from this study indicate that the assay is sensitive and provide a
      relatively simple approach to assay TDG cleaved from blood proteins at relatively
      long time frames (21-45 days) after HD exposure. The utility of the method has
      been demonstrated in vivo in a non-human primate and pig HD exposure model.

PMID- 15239849
TI  - Standard operating procedure for immunuslotblot assay for analysis of DNA/sulfur
      mustard adducts in human blood and skin.
AB  - A standard operating procedure has been developed for an immunoslotblot assay of
      sulfur mustard adducts to DNA in human blood and skin for use in a field
      laboratory. A minimum detectable level of exposure of human blood in vitro (> or
      = 50 nM) sulfur mustard is feasible with the assay. In the case of human skin, a
      1 s exposure to saturated sulfur mustard vapor (830 mg/m(-3)) could still be
      detected.

PMID- 15239848
TI  - Procedure for monitoring exposure to sulfur mustard based on modified edman
      degradation of globin.
AB  - A procedure for the modified Edman degradation of globin for determination of
      sulfur mustard adducts to the N-terminal valine residue in human hemoglobin has
      been developed for use under field laboratory conditions. The minimum detectable
      exposure level of human blood (in vitro) to sulfur mustard using this procedure
      is 100 nM. The interindividual and intraindividual variabilities of the procedure
      were acceptable (standard deviation < 10% and < 20%, respectively). The procedure
      could be properly set up and carried out in another laboratory within one working
      day, demonstrating its robustness.

PMID- 15239850
TI  - Quantitation of biomarkers of exposure to nitrogen mustards in urine from rats
      dosed with nitrogen mustards and from an unexposed human population.
AB  - The nitrogen mustards bis(2-chloroethyl)ethylamine (HN1), bis(2
      chloroethyl)methylamine (HN2), and tris(2-chloroethyl)amine (HN3) have the
      potential to be used as chemical terrorism agents because of their extreme
      vesicant properties. We modified a previously reported method to incorporate
      automated solid-phase extraction, improve chromatography, and include the urinary
      metabolite for HN3. The improved method was used to measure levels of the urinary
      metabolites N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA), and
      triethanolamine (TEA) in rats dosed with HN1, HN2, and HN3, respectively, and to
      establish background levels of EDEA, MDEA, and TEA in human urine samples from a
      population with no known exposure to nitrogen mustards. Rat dosing experiments
      confirmed that EDEA, MDEA, and TEA could be detected in urine for at least 48 h
      after exposure to HN1, HN2, and HN3, respectively. Substantial amounts of EDEA
      (89 ng/mL), MDEA (170 ng/mL), and TEA (1105 ng/mL) were measured in the urine of
      rats exposed to 10 mg HN1, HN2, and HN3, respectively, 48 h after exposure. The
      background concentrations for TEA in the human population ranged from below the
      limit of detection (LOD 3 ng/mL) to approximately 6500 ng/mL. Neither EDEA (LOD
      0.4 ng/mL) nor MDEA (LOD 0.8 ng/mL) was detected above the LOD in the human
      samples.

PMID- 15239851
TI  - Quantitation of the sulfur mustard metabolites 1,1'-sulfonylbis[2
      (methylthio)ethane] and thiodiglycol in urine using isotope-dilution Gas
      chromatography-tandem mass spectrometry.
AB  - Sulfur mustard (HD), or bis(2-chloroethyl)sulfide, has several urinary
      metabolites that can be measured to assess human exposure. These metabolites
      include the simple hydrolysis product thiodiglycol (TDG) and its oxidative
      analogue, TDG-sulfoxide, as well as metabolites of the glutathione/b-lyase
      pathway 1,1'-sulfonylbis[2-(methyl-sulfinyl)ethane] (SBMSE) and 1-methyl-sulfinyl
      2-[(methylthio)ethyl-sulfonyl]ethane (MSMTESE). Current methods focus on either
      the TDG or the b-lyase metabolites. We have developed a single method that
      measures products of both metabolic branches, with the reduced compound of SBMSE
      and MSMTESE, 1,1'-sulfonylbis [2(methylthio)ethane] (SBMTE), as the definitive
      analyte and TDG as a confirmation analyte. Sample preparation included b
      glucuronidase hydrolysis for TDG-glucuronide conjugates, titanium trichloride
      reduction of sulfoxides to SBMTE and TDG, solid-phase extraction, and a chemical
      derivatization. We analyzed samples using gas chromatography-tandem mass
      spectrometry with quantitation using isotope-dilution calibration. The method
      limits of detection for TDG and SBMTE were 0.5 ng/mL and 0.25 ng/mL,
      respectively, with relative standard deviations of less than 10%. Urine samples
      from individuals with no known exposure to mustard agent HD had measurable
      concentrations of TDG, but no SBMTE was detected. The geometric mean
      concentration of TDG was 3.43 ng/mL, with concentrations ranging from < 0.5 ng/mL
      to 20 ng/mL.

PMID- 15239852
TI  - Retrospective detection of exposure to sulfur mustard: improvements on an assay
      for liquid chromatography-tandem mass spectrometry analysis of albumin-sulfur
      mustard adducts.
AB  - We here report on the further development of the method comprising the pronase
      digestion of albumin alkylated by sulfur mustard and the subsequent mass
      spectrometric analysis of an adducted tripeptide. This includes significant
      improvements in both the albumin isolation procedure and the automation of the
      microliquid chromatography-electrospray-tandem mass spectrometric analysis. We
      also report on the results of a small reference range study, in which we have
      established that there are no detectable interferences in sera from unexposed
      individuals.

PMID- 15239853
TI  - A rapid, sensitive method for the quantitation of specific metabolites of sulfur
      mustard in human urine using isotope-dilution gas chromatography-tandem mass
      spectrometry.
AB  - Sulfur mustard agent (HD) (2,2'-dichloroethyl sulfide), a Schedule I compound on
      the Chemical Weapons Convention Schedule of Chemicals, remains a public health
      concern because it is simple to synthesize and it is in the chemical weapon
      stockpiles of several countries. A sensitive, rapid, accurate, and precise method
      was developed to quantitate trace levels of 1,1'-sulfonylbis [2-(methylthio)
      ethane] (SBMTE) in human urine as a means of assessing exposure to HD. The method
      used immobilized liquid-liquid extraction with diatomaceous earth, followed by
      the analysis of the urine extract using isotope-dilution gas chromatography
      tandem mass spectrometry. Relative standard deviations were less than 8.6% at 1
      ng/mL and 3.6% at 20 ng/mL. The limit of detection for SBMTE was 0.038 ng/mL in
      0.5 mL of urine.

PMID- 15239854
TI  - Analysis of beta-lyase metabolites of sulfur mustard in urine by electrospray
      liquid chromatography-tandem mass spectrometry.
AB  - A method is described for the analysis of b-lyase metabolites of sulfur mustard,
      1-methylsulfinyl-2- [2-(methylthio)ethylsulfonyl]ethane and 1,1'-sulfonylbis [2
      (methylsulfinyl)ethane], in human urine. The analytes were concentrated from
      urine on an ENV+ solid-phase extraction cartridge and analyzed by liquid
      chromatography-positive ion electrospray-tandem mass spectrometry in the selected
      reaction monitoring mode. Quantitation was performed against deuterated internal
      standards. Limits of detection were 0.1-0.5 ng/mL. The metabolites were detected
      in samples of urine from human casualties of sulfur mustard poisoning. The method
      provides a simpler alternative to gas chromatography-tandem mass spectrometry
      analysis, avoiding the need for reduction to less polar analytes.

PMID- 15239855
TI  - Analysis of the sulfur mustard metabolite 1,1'-sulfonylbis[2-S-(N
      acetylcysteinyl)ethane] in urine by negative ion electrospray liquid
      chromatography- tandem mass spectrometry.
AB  - A method is described for the analysis of the sulfur mustard metabolite 1,1'
      sulfonylbis[2-S-(N-acetylcysteinyl)ethane] in human urine. The analyte was
      concentrated from urine on a polymeric SPE cartridge and analyzed by liquid
      chromatography-negative ion electrospray tandem mass spectrometry in the selected
      reaction monitoring mode. The limit of detection was 0.5-1 ng/mL. The metabolite
      was detected at concentrations close to the detection limit in samples of urine
      from two casualties accidentally exposed to sulfur mustard from a First World War
      munition.

PMID- 15239856
TI  - Quantitation of fluoride ion released sarin in red blood cell samples by gas
      chromatography-chemical ionization mass spectrometry using isotope dilution and
      large-volume injection.
AB  - A new method for measuring fluoride ion released isopropyl
      methylphosphonofluoridate (sarin, GB) in the red blood cell fraction was
      developed that utilizes an autoinjector, a large-volume injector port (LVI),
      positive ion ammonia chemical ionization detection in the SIM mode, and a
      deuterated stable isotope internal standard. This method was applied to red blood
      cell (RBC) and plasma ethyl acetate extracts from spiked human and animal whole
      blood samples and from whole blood of minipigs, guinea pigs, and rats exposed by
      whole-body sarin inhalation. Evidence of nerve agent exposure was detected in
      plasma and red blood cells at low levels of exposure. The linear method range of
      quantitation was 10-1000 pg on-column with a detection limit of approximately 2
      pg on-column. In the course of method development, several conditions were
      optimized for the LVI, including type of injector insert, injection volume,
      initial temperature, pressure, and flow rate. RBC fractions had advantages over
      the plasma with respect to assessing nerve agent exposure using the fluoride ion
      method especially in samples with low serum butyrylcholinesterase activity.

PMID- 15239857
TI  - Improvements of the fluoride reactivation method for the verification of nerve
      agent exposure.
AB  - One of the most appropriate biomarkers for the verification of organophosphorus
      nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase
      (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE
      enzyme by incubation with fluoride ions, after which the resulting
      organophosphonofluoridate can be analyzed with gas chromatography-mass
      spectrometry (GC-MS). This paper describes recent improvements of the fluoride
      induced reactivation in human plasma or serum samples by enhancing the sample
      preparation with new solid-phase extraction cartridges and the MS analysis with
      large volume injections. Analysis is performed with thermal desorption GC with
      either mass selective detection with ammonia chemical ionization or high
      resolution MS with electron impact ionization. The organophosphorus chemical
      warfare agents analyzed in this study are O-ethyl S-2-diisopropylaminoethyl
      methylphosphonothiolate, ethyl methylphosphonofluoridate, isopropyl
      methylphosphonofluoridate (sarin, GB), O-ethyl N,N
      dimethylphosphoramidocyanidate, ethyl N,N-dimethylphosphoramidofluoridate, and
      cyclohexyl methylphosphonfluoridate. Detection limits of approximately 10 pg/mL
      plasma were achieved for all analytes, which corresponds to 0.09% inhibition with
      GB on a sample with normal BuChE levels.

PMID- 15239858
TI  - Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin,
      VX, and Russian VX in human urine using isotope-dilution gas chromatography
      tandem mass spectrometry.
AB  - Organophosphorus nerve agents are among the most toxic organic compounds known
      and continue to be a threat for both military and terrorist use. We have
      developed an isotope-dilution gas chromatography-tandem mass spectrometric (GC-MS
      MS) method for quantitating the urinary metabolites of the organophosphorus nerve
      agents sarin (GB), soman (GD), VX, Russian VX (RVX), and cyclohexylsarin (GF).
      Urine samples were acidified, extracted into ether-acetonitrile, derivatized by
      methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection
      were less than 1 micro g/L for all analytes.

PMID- 15239859
TI  - Identification and characterization of the major huperzine a metabolite in rat
      blood.
AB  - Huperzine A (Hup A) is under investigation as a treatment of Alzheimer's disease
      because of its properties of reversible and specific AChE inhibition. It has
      additional interesting pharmacological effects such as the protection of primary
      neuronal cells isolated from embryonic rat brains from glutamate-induced
      toxicity. We have isolated a new compound which has similar absorbance
      characteristics as Hup A from blood of rats administered Hup A. Monitoring the
      effluent from reversed-phase high-performance liquid chromatography (RP-HPLC) of
      blood collected 60 min after Hup A treatment at an absorbance of 308 nm
      (lambdamax for Hup A), yielded a peak height and area for this compound that was
      approximately 1.4-fold the initial Hup A peak. The compound was isolated from RP
      HPLC fractions from blood and liver for analysis by mass spectrometry and nuclear
      magnetic resonance (NMR). The compound gave an (M+H)+ ion with m/z 259 in
      positive ion mode, yielding a molecular weight (MW) of 258. If derived from Hup A
      (MW 242), the change in MW indicates a mass gain of 16. This would be consistent
      with the addition of a single oxygen or a hydroxylation. To determine the
      location of the modification, it was examined by 1H NMR, and it was found that
      the added mass was due to a single epoxidation yielding 13,14-epoxy Hup-A.

PMID- 15239860
TI  - Gas chromatographic-mass spectrometric determination of british anti-lewisite in
      plasma.
AB  - British anti-Lewisite (BAL) (2,3-dimercapto-1-propanol) is a potential
      therapeutic compound when used against the effects of cutaneous sulfur mustard,
      and a method for its determination in plasma has been developed. BAL and the
      internal standard (IS) ethane dithiol were isolated from plasma samples through
      solid-phase extraction and then reacted with 1-pentafluoropropionylimidazole,
      forming stable pentafluoropropionyl derivates that are sensitive to gas
      chromatographic-mass spectrometric analysis. Examination of concentration versus
      peak-area ratios of the BAL and IS derivatives demonstrated the method to be
      linear over a concentration range of 0.48 to 124 ng/mL in plasma when fit to a
      weighted (1/y2) least-squares regression. Correlation coefficients were 0.9943 to
      0.9995 for six runs, and coefficients of variation (CV) were 2.5 to 8.7% over the
      eight concentrations tested. The intra- and interday accuracy and precision of
      this method was measured by examining six groups of eight unknown test samples (n
      = 6). Intraday accuracy, as expressed by percent error, was found to range from 
      15.4 to 0.21%, whereas the precision, expressed as %CV, was less than 9.8% over
      all sample concentrations. Interday test unknown sample results were similar in
      that the accuracy was shown to be -7.1 to 0.4%, and precision was 4.7 to 9.5%.
      BAL levels in frozen plasma (-70 degrees C) remained constant for more than 14
      days with a CV of less than 10% for the eight concentrations tested. The data
      indicate that the method will provide accurate and precise determination of BAL
      at concentrations down to approximately 1 ng/mL in plasma. This procedure has
      been applied to determine preliminary time-concentration profile studies of BAL
      in the hairless guinea pig.

PMID- 15239861
TI  - Analysis of the enantiomers of VX using normal-phase chiral liquid chromatography
      with atmospheric pressure chemical ionization-mass spectrometry.
AB  - The chemical warfare nerve agent O-ethyl S-(2-diisopropylaminoethyl)
      methylphosphonothioate (VX) is a mixture of two enantiomers resulting from the
      chiral center at the phosphorus atom. Significant differences exist in the
      reported toxicity and acetylcholinesterase inhibition rates of the two
      enantiomers. This makes the ability to distinguish between them desirable for
      either toxicological studies or the development of antidotal therapies. Using a
      Chiralcel OD-H column with normal-phase liquid chromatography, the enantiomers
      were baseline resolved in less than 7 min. Atmospheric pressure chemical
      ionization was utilized as the interface between a liquid chromatograph and mass
      spectrometer. The mass spectra of the two enantiomers were virtually identical.
      The protonated molecule was readily observed at m/z 268. VX was incubated with
      human plasma for 13 min, followed by hexane extraction. The areas of the first
      and second eluting VX enantiomers decreased by approximately 40% and 6%,
      respectively, when compared with VX-spiked plasma samples that were not allowed
      an incubation phase. Currently, research by others has been directed towards the
      identification, isolation, and possible modification of enzymes capable of
      hydrolyzing VX. The method presented here provides an analytical tool capable of
      monitoring the stereospecificity of enzymes that react with VX.

PMID- 15239862
TI  - Telemedicine in acute plastic surgical trauma and burns.
AB  - BACKGROUND: Telemedicine is a relatively new development within the UK, but is
      increasingly useful in many areas of medicine including plastic surgery. Plastic
      surgery centres often work on a hub-and-spoke basis with many district hospitals
      referring to one tertiary centre. The Queen Victoria Hospital is one such centre
      receiving calls from more than 28 hospitals in the Southeast of England resulting
      in approximately 20 referrals a day. OBJECTIVE: A telemedicine system was
      developed to improve trauma management. This study was designed to establish
      whether digital images were sufficiently accurate enough to aid decision-making.
      A store-and-forward telemedicine system was devised and the images of 150 trauma
      referrals evaluated in terms of injury severity and operative priority by each
      member of the plastic surgical team. RESULTS: Correlation scores for assessed
      images were high. Accuracy of "transmitted image" in comparison to injury on
      examination scored > 97%. Operative priority scores tended to be higher than
      injury severity. CONCLUSIONS: Telemedicine is an accurate method by which to
      transfer information on plastic surgical trauma including burns.

PMID- 15239863
TI  - A cost-effectiveness analysis of conventional and nurse-led telephone follow-up
      after nasal septal surgery.
AB  - BACKGROUND: The need to bring down costs while maintaining a high standard of
      care has led to the expansion in the role of nurses in recent years. METHODS: We
      present results of cost-effectiveness analysis of conventional and nurse-led
      telephone follow-up after nasal septal surgery. RESULTS AND CONCLUSIONS: Our
      results indicate that the substitution of nurse-led telephone follow-up for
      conventional out-patient follow-up has the potential for substantial cost
      reduction and decreased out-patient access times in the NHS.

PMID- 15239864
TI  - Current management in pharyngeal pouch surgery by UK otorhinolaryngologists.
AB  - INTRODUCTION: Many surgical techniques have been described for the treatment of
      pharyngeal pouches but there is no single treatment of choice. The aim of this
      study was to determine current practice in pharyngeal pouch surgery by UK
      otolaryngologists. METHODS: A postal questionnaire was sent to all UK-based
      consultant members of the British Association of Otolaryngologists - Head and
      Neck Surgeons (BAO-HNS). RESULTS: Endoscopic stapling diverticulotomy is the most
      commonly performed procedure, performed by 89% of surgeons, followed by excision.
      Of those consultants that considered there to be a treatment of choice, 83%
      stated endoscopic stapling as their preference. Practices differ regarding the
      insertion of nasogastric tubes after endoscopic procedures and the need for
      postoperative barium studies. The length of in-patient stay tends to be short
      with 80% of surgeons discharging patients by day 2. CONCLUSIONS: Endoscopic
      stapling diverticulotomy is now the most commonly performed procedure for the
      management of pharyngeal pouches by UK otolaryngologists and is now considered by
      many to be the treatment of choice.

PMID- 15239865
TI  - Life-threatening necrotizing fasciitis of the neck: an unusual consequence of a
      sore throat.
AB  - BACKGROUND: Necrotizing fasciitis is life-threatening bacterial infection which
      spreads with frightening speed along the fascial planes resulting in extensive
      tissue necrosis and often death. The infection is caused by either Group A
      streptococci or a combination of aerobic and anaerobic bacteria. Necrotizing
      fasciitis of the neck is rare and commonly has a dental origin. CASE REPORT: Here
      we present a unique case of the condition that was preceded by a sore throat in a
      young immunocompetent woman. We also describe, for the first time, a successful
      outcome involving primary skin closure and daily irrigation of the wound with
      hydrogen peroxide.

PMID- 15239866
TI  - An unusual case of haemorrhagic median neuropathy.
AB  - The authors describe a rare case of carpal tunnel syndrome secondary to
      intraneural haemorrhage of the median nerve.

PMID- 15239867
TI  - A safe, simple and cost-effective protocol for blood transfusion in primary total
      knee replacement.
AB  - BACKGROUND: Patients undergoing total knee replacement (TKR) in the UK usually
      have either blood cross-matched or have an auto-transfusion of drained blood
      postoperatively. A previous retrospective audit of blood requirements in patients
      who had undergone primary TKR showed that a large amount of cross-matched blood
      was wasted as the CT ratio (ratio of number of units of blood cross-matched to
      number of units transfused) of 4.9:1 was obtained. The range recommended by the
      Blood Transfusion Society is 2:1 to 3:1. METHODS: A protocol was introduced to
      group and save plus antibody screen for all patients and to cross-match 2 units
      of blood pre-operatively in patients with either a haemoglobin of less than 12.5
      g/dl or with multiple red cell antibodies in their blood. The trigger point for
      blood transfusion postoperatively was also reduced from 9.0 g/dl to 8.0 g/dl,
      unless the patient was clinically symptomatic. RESULTS: A further prospective
      study involving 50 patients was carried out using the new protocol. Five patients
      required cross-matching pre-operatively, three with haemoglobin less than 12.5
      g/dl and two with multiple red cell antibodies. Postoperatively, the patients
      with haemoglobin of less than 12.5 g/dl required blood transfusion of 2 units
      each, reducing the CT ratio to 1.7:1. The patients with red cell antibodies did
      not require a blood transfusion. CONCLUSIONS: The benefits from above protocol
      are 2-fold: patient safety, as risks of transfusion are avoided; and cost saving,
      in regards to haematology technician time and auto-transfusion sets which cost
      around pound 70 each.

PMID- 15239869
TI  - Infection after total hip arthroplasty.
AB  - Total hip joint replacement offers dramatic improvement in the quality of life
      but deep infection is the most feared complication of this procedure. The
      infection threatens the function of the joint, the preservation of the limb, and
      occasionally even the life of the patient. For the surgeon it is a disastrous
      anticlimax, which follows a procedure that may have given the patient freedom
      from pain and increased mobility.

PMID- 15239868
TI  - Timing of antibiotic prophylaxis in surgery for adult hip fracture.
AB  - BACKGROUND: Antibiotic prophylaxis is widely used in surgery for hip fractures.
      METHODS AND RESULTS: In a retrospective study of case notes of 100 patients,
      frequent inaccuracies in dose administration were observed. This was applicable
      to both the pre-operative and the postoperative doses. Longer time intervals
      between the doses, failure to administer the prescribed doses, and failure of
      proper documentation were observed. CONCLUSIONS: Improvement in the awareness of
      staff and timely administration of prophylactic antibiotic has resulted from this
      study.

PMID- 15239870
TI  - Septic arthritis of the knee by Salmonella montevideo.
AB  - We describe a case of salmonella septic arthritis of the knee in a middle-aged
      woman with the following predisposing conditions: long-term corticosteroids and
      microscopic collagenous colitis. The patient presented with enteritis caused by
      the same strain 3 months before the arthritis. The first series of cultures were
      negative and the possibility of a chronic carriage of the disease was not
      suspected initially. The patient was treated with antibiotics and arthroscopic
      washouts; the corticosteroid treatment was maintained. There was a progressive
      clinical and microbiological improvement and the patient was discharged 3 weeks
      later. Salmonella montevideo is a rare form of salmonella and is known to be
      associated with tropical fishes, reptiles and imported species.

PMID- 15239871
TI  - The impact of training on outcomes in primary vascular access surgery.
AB  - BACKGROUND: There is evidence that the outcome of arteriovenous fistula surgery
      is dependent on the surgeon performing the operation. Vascular access surgery
      provides excellent technical training for surgical trainees. The effect of
      surgical trainees on the outcome of fistulas was evaluated. METHODS: The grade of
      the main operator for all first attempted (primary) upper limb arteriovenous
      fistulas, between February 1998 and August 2001, was identified. Median follow-up
      was 18.0 months (IQR, 6.5-30.1 months). Successful use of fistula for dialysis,
      fistula patency and survival were assessed. RESULTS: 441 primary fistulas were
      formed in the study period. Median age was 67.5 years (IQR, 54.0-75.2 years). 71%
      of all fistulas were formed at the wrist. Trainees performed 31.1% of all
      operations. The two groups (trainees and consultants) were well matched for age,
      sex, diabetes, and fistula type. Only 70.5% of patients proceeded to long-term
      haemodialysis. There were no significant differences in the successful use of AVF
      for dialysis or patency rates between the two groups. One and two year fistula
      survival in this group was 87.7% and 78.3% for trainees and 80.8% and 71.1% for
      consultants (P = 0.288 log rank). CONCLUSIONS: Surgical trainees can perform
      primary AVF surgery without significantly reducing fistula outcomes. Vascular
      access surgery can be utilised as a training operation.

PMID- 15239872
TI  - Randomised clinical trial of elective re-siting of intravenous cannulae.
AB  - INTRODUCTION: Peripheral venous thrombophlebitis (PVT) represents a considerable
      source of iatrogenic morbidity, occurring in about 20% of hospital in-patients.
      The aim of this prospective randomised study was to investigate the effect of
      elective change of intravenous cannulae on the incidence of PVT in hospital in
      patients. PATIENTS AND METHODS: General medical and surgical inpatients requiring
      intravenous therapy were randomised into control (n = 26) or study (n = 21)
      groups. Cannulae in the control group were only removed if the site became
      painful, the cannula dislodged, or there were signs of PVT. Cannulae in the study
      group were changed electively every 48 h. All patients were examined daily for
      signs of PVT. RESULTS: Peripheral venous thrombophlebitis developed in 11/26
      patients in the control group and 1/21 patients in the study group (P = 0.003).
      Elective change of cannulae did not significantly increase the total number of
      cannulae sited (41 cannulae in the control group versus 43 in the study group).
      CONCLUSIONS: Elective change of cannulae resulted in a significant reduction in
      the incidence of infusion phlebitis. The authors recommend that elective re
      siting of intravenous cannulae becomes standard practice for all patients
      requiring intravenous therapy.

PMID- 15239873
TI  - Testicular pain as the initial presentation of testicular neoplasms.
AB  - OBJECTIVES: Testicular neoplasms are reported to present with testicular pain in
      0.01-10% of patients. The diagnosis of tumour may, therefore, not be considered
      immediately with this mode of presentation, leading potentially to delays in
      diagnosis and poorer prognosis or scrotal exploration for suspected torsion. The
      objective of this study was to assess the incidence of pain as the presentation
      of testicular neoplasms. PATIENTS AND METHODS: A retrospective case note analysis
      of all patients undergoing radical orchidectomy over an 11-year period in Hull,
      UK was performed. Data on presenting symptoms, histology and clinical stage were
      collected. RESULTS: It was found that 23.5% of all patients analysed (27 of 115)
      presented with testicular pain, but that this did not appear to correlate with
      any particular histological sub-type of neoplasm or stage of disease. However,
      those presenting with germ cell tumours and testicular pain were more likely to
      suffer disease relapse than those presenting with painless testicular enlargement
      (1 6% compared to 2.6%). CONCLUSIONS: Testicular neoplasms should be considered
      earlier in patients presenting with testicular pain, as this may be more common
      than previously reported.

PMID- 15239874
TI  - Is high cord radical orchidectomy always necessary for testicular cancer?
AB  - BACKGROUND: Radical high cord inguinal orchidectomy remains the standard for
      diagnosis, staging and treatment of testicular neoplasms. Low cord orchidectomy
      is an alternative to the high cord orchidectomy. OBJECTIVE: To test the
      hypothesis that there is no difference in relapse rate or mortality between high
      and low cord orchidectomy for the treatment of testicular cancer. METHODS: A
      retrospective study was undertaken of all orchidectomies performed for testicular
      cancer at our hospital between 1981 and 2002. RESULTS: Overall, 120 high cord
      orchidectomies and 102 low cord orchidectomies were performed for testicular
      cancer between 1981 and 2002 at our hospital. Analysis showed that there was no
      significant difference in the mean age of the patients, the rate of relapse, mean
      time to relapse or survival between surgical approach for stage 1 tumours. For
      stage 2-4 tumours, there were not sufficient numbers to comment on the
      statistical significance of relapse or survival differences. CONCLUSIONS: The
      trend suggests that there is no statistically significant difference in the rate
      of relapse and mortality between high and low cord orchidectomy for clinically
      stage 1 tumours. We would, therefore, advocate either a high or low cord
      orchidectomy for clinically stage 1 tumours.

PMID- 15239875
TI  - Significance of routine digital rectal examination in adults presenting with
      abdominal pain.
AB  - AIM: Routine digital rectal examination (DRE) in children with abdominal pain has
      slowly gone out of practice but is still performed routinely in adults. This
      study was undertaken to assess the significance of routine DRE in adults with
      acute abdominal pain. PATIENTS AND METHODS: A total of 100 consecutive adults
      admitted to the emergency surgical unit with acute abdominal pain were studied
      prospectively. Following DRE, patients who were willing to participate in the
      study were requested to complete an anonymous questionnaire. The house officer
      conducted the rectal examination at admission and also completed an evaluation
      sheet. RESULTS: A working diagnosis of acute appendicitis in 38 patients and
      gastroduodenal, pancreatobiliary pathology in 24 patients was made. DRE did not
      alter clinical diagnosis or initial management in any of the 100 patients.
      Routine DRE did not detect any unrelated pathology. Of the patients, 93 wanted to
      know why rectal examination was required. Overall, 78 patients rated the DRE as
      uncomfortable. Although 43 were willing for DRE as a routine, 54 patients
      preferred to have the DRE at the time of other bowel tests rather than at the
      time of the emergency admission. CONCLUSIONS: Various routine medical procedures
      have given way to evidence-based practice. This study has demonstrated the
      limited role of routine DRE in adults with no anorectal or GI symptoms during
      their initial evaluation for acute abdominal pain.

PMID- 15239876
TI  - NICE news in the Annals.

PMID- 15239877
TI  - Laparoscopic surgery for colorectal cancer.

PMID- 15239878
TI  - A first curriculum framework for surgical SHOs designed by the Royal College of
      Surgeons of England.

PMID- 15239879
TI  - Integrating refugee doctors into the NHS.

PMID- 15239880
TI  - Data handling and dissemination in proteomics and genomics.

PMID- 15239881
TI  - Transcriptomics and proteomics of human skin.
AB  - The epidermis protects the organism against physical, chemical and biological
      challenges, and it acts as a signalling interface between the environment and the
      body. In order to perform these functions, the epidermal keratinocytes express a
      wide range of genes, several of which have been characterised previously.
      Recently, significant progress has been made in the large-scale analysis of
      keratinocyte gene expression, enabling a more profound insight into keratinocyte
      biology and human skin diseases. Transcriptome analysis--serial analysis of gene
      expression (SAGE) and microarrays--and proteome analysis have been performed on
      intact human epidermis and on keratinocytes cultured in model systems that mimic
      normal and diseased human epidermis. Here, we review the current state of large
      scale gene expression analysis of human skin, with an emphasis on SAGE and
      complementary DNA microarrays. The merits and limitations of various approaches
      (transcriptomics versus proteomics) are discussed and the practical issues such
      as sample preparation from skin biopsies, and the use of in vitro models are
      briefly addressed.

PMID- 15239882
TI  - Recent developments in the engineering of zinc finger proteins.
AB  - Within the last 20 years, the understanding of the biology of the 'classical' or
      Cys(2)His(2) zinc finger domain has progressed rapidly from the initial
      identification of the zinc finger as a repetitive zinc-binding motif in
      transcription factors to its use in biotechnology. The domain is the most
      abundant DNA-binding motif in the human genome and is a component of many key
      eukaryotic transcription factors involved in growth and development. Numerous
      structures now exist for this domain and its mode of action is known in a variety
      of zinc finger-DNA complexes. Application of this knowledge has led to the
      development of 'designer' transcription factors where zinc fingers have been
      engineered to bind desired DNA sequences. Recently, advances have been made in
      this field that potentially allow the targeting of any DNA site. Consideration of
      chromatin structure and the use of effector domains in these 'designer'
      transcription factors have made possible the regulation of a number of endogenous
      genes. These advances in the customised regulation of genes will be discussed in
      detail, as well as the potential to use these proteins in functional genomics and
      gene therapy applications.

PMID- 15239883
TI  - Genome analysis technologies: towards species identification by genotype.
AB  - Traditional identification of species has been based on phenotypic traits,
      although it is clear that, theoretically, genotype-based classification is more
      accurate. This is especially the case for microorganisms which possess less
      identifiable traits and are more easily influenced by environment. Therefore,
      technology that allows identification of species based on genotype is highly
      desirable. Whole genome sequencing can provide a sufficient amount of information
      and can be determinative for this purpose but is very impractical for routine
      use. Thus, a competent technology is needed that allows a reproducible reduction
      in the amount of information required about a whole genome, while still providing
      sufficiently accurate identification. It is almost imperative for such a
      technology to be of a high cost-performance and of easy handling. Universality
      and portability are also strongly desired. Based on these criteria, the current
      state of genome analysis technologies are reviewed. Among various methodologies
      discussed here, amplified fragment length polymorphism (AFLP), genome profiling
      (GP) and microarrays are the subject of particular attention. As species
      identification is a base for most fields of biology including microbiology,
      ecology, epidemiology and for various biotechnologies, it is of paramount
      importance to establish a more efficient, easily handled and more objective
      methodology, in parallel with conventional phenotype-based methodologies. GP is
      currently considered to have the most optimal nature for identification of
      species since it can reproducibly reduce a huge amount of genome information to a
      manageable size by way of random polymerase chain reaction and can extract a
      sufficient amount of information for species identification from the DNA
      fragments thus profiled by temperature gradient gel electrophoresis. The
      potential ability of DNA microarrays for this purpose is also discussed and
      promises much for the future.

PMID- 15239884
TI  - Shedding light on health and disease using molecular beacons.
AB  - The detection and identification of pathogens is often painstaking due to the low
      abundance of diseased cells in clinical samples. The genomic sequences of the
      pathogen can be amplified through methods such as the polymerase chain reaction
      and nucleic acid sequence-based amplification, but the nucleic acid targets are
      often lost among other unintended products of amplification. Novel nucleic acid
      probes known as molecular beacons have been developed allowing for the rapid and
      specific detection of genetic markers of a disease. Molecular beacons are hairpin
      forming oligonucleotides labelled at one end with a quencher and at the other end
      with a fluorescent reporter dye. In the absence of target, the fluorescence is
      quenched. In the presence of target, the hairpin structure opens upon
      beacon/target hybridisation, resulting in the restoration of fluorescence. The
      ability to transduce target recognition into a fluorescence signal with high
      signal-to-background ratio, coupled with an improved specificity, has allowed
      molecular beacons to enjoy a wide range of biological and biomedical
      applications. Here, we describe the basic features of molecular beacons, review
      their applications in disease detection and diagnosis and discuss some of the
      issues and challenges of in vivo studies. The aim of this paper is to foster the
      development of new molecular beacon-based assays and to stimulate the application
      of this technology in laboratory and clinical studies of health and disease.

PMID- 15239885
TI  - Single DNA molecule analysis: applications of molecular combing.
AB  - Dynamic changes to the genomic structure and to the DNA replication programme are
      important determinants of normal and abnormal cell development. To understand
      these changes and how they vary from cell to cell, single DNA molecules from both
      normal and abnormal cell populations must be examined and compared. Physical
      characterisation of single genomes at the kilobase level of resolution over large
      genomic regions is possible with molecular combing technology. An array of combed
      single DNA molecules is prepared by stretching molecules attached by their
      extremities to a silanised glass surface with a receding air-water meniscus. By
      performing fluorescent hybridisation on combed DNA, genomic probe position can be
      directly visualised, providing a means to construct physical maps and detect
      micro-rearrangements. Single-molecule DNA replication can also be monitored
      through fluorescent detection of incorporated nucleotide analogues on combed DNA
      molecules. These and other single-molecule applications of molecular combing are
      discussed in this paper and future developments of the technology are considered.

PMID- 15239886
TI  - One by one: Single molecule tools for genomics.
AB  - Much of the effort in any genomics programme arises from the need to generate and
      purify large numbers of identical molecules, since most analytical tools rely on
      the analysis of bulk DNA. Biological steps such as bacterial cloning--commonly
      used to prepare bulk samples of defined DNA fragments--are capricious and
      introduce their own restrictions and distortions. The analysis of single
      molecules, either directly or by in vitro enzymatic amplification, makes possible
      the examination of native genomic DNA without the complications and restrictions
      of biological propagation. Techniques already exist for the in vitro propagation
      of genomic fragments and for genome mapping, and offer the advantages of speed,
      flexibility and predictable behaviour. Single molecule sequencing, for which many
      approaches are being developed, is more challenging, but offers even greater
      rewards in terms of throughput and read length.

PMID- 15239889
TI  - Just click on the mouse!
AB  - The mouse genome is being sequenced in an efficient, coordinated manner. The map
      is complete and an assembly of whole genome shotgun data is available at a click
      of the mouse. In the final finished sequence phase, it seems a targeted approach
      would be more useful than random coverage. There are currently rich pickings
      available for mouse geneticists--that is to say, as long as their particular
      region of interest has been covered. Hard lessons learnt from the Human Genome
      Project have been put into practice, resulting in the elucidation of the mouse
      genome taking place with greater efficiency. The various genome centres have
      worked with coordination and a common strategy to generate a draft of the mouse
      genome in under a year, an achievement that would not have been deemed plausible
      a few years ago.

PMID- 15239890
TI  - Analysis of protein-protein proximities using the split-ubiquitin system.
AB  - The split-ubiquitin system is a fragment complementation assay that is based on a
      conditional proteolysis design. The system has been used to study protein-protein
      interactions between membrane proteins and to screen for new interaction partners
      for transcription factors. This paper outlines the recent progress in the split
      ubiquitin technology that has been made possible through the development of new
      reporter proteins.

PMID- 15239892
TI  - Adapting chromophore-assisted laser inactivation for high throughput functional
      proteomics.
AB  - Recent advances in genomics and proteomics have generated a change in emphasis
      from hypothesis-based to discovery-based investigations. Genomic and proteomic
      studies based on differential expression microarrays or comparative proteomics
      often provide many potential candidates for functionally important roles in
      normal and diseased cells. High throughput technologies to address protein and
      gene function in situ are still necessary to exploit these emerging advances in
      gene and protein discovery in order to validate these identified targets. The
      pharmaceutical industry is particularly interested in target validation, and has
      identified it as the critical early step in drug discovery. An especially
      powerful approach to target validation is a direct protein knockdown strategy
      called chromophore-assisted laser inactivation (CALI) which is a means of testing
      the role of specific proteins in particular cellular processes. Recent
      developments in CALI allow for its high throughput application to address many
      proteins in tandem. Thus, CALI may have applications for high throughput
      hypothesis testing, target validation or proteome-wide screening.

PMID- 15239891
TI  - Morpholino phosphorodiamidate oligonucleotides in zebrafish: a recipe for
      functional genomics?
AB  - Morpholino phosphorodiamidate anti-sense oligonucleotides (MPOs) have recently
      emerged as a tool for gene-specific knockdown. MPOs have a great potential for
      both therapeutic applications and functional genomics. In particular, zebrafish
      are well suited for gene function studies using MPOs owing to their rapid
      external development, transparent embryos and the ease of delivery of the
      intervening MPOs. This paper describes principles of MPO action and the
      application of MPOs for gene function studies and therapeutics. In the field of
      functional genomics, the MPO strategy has been most successfully used to study
      gene function in zebrafish. Over 35 mutations have been successfully phenocopied
      and over 30 novel gene functions have been analysed in zebrafish using MPOs
      during the last two years. The essential controls that are required to avoid
      misinterpretation of experimental data when using MPOs for gene function analysis
      will also be described.

PMID- 15239893
TI  - Regulation of alternative pre-mRNA splicing.
AB  - The first wave of bioinformatic studies that followed genome and complementary
      DNA sequencing projects revealed that alternative splicing of messenger RNA
      precursors (pre-mRNAs) contributes substantially to transcriptome complexity in
      higher eukaryotes. Together with the realisation of the impact of the process on
      cell differentiation, development and disease, these studies portray alternative
      splicing as a fundamental component of gene regulation. Both detailed mechanistic
      studies and genome-wide analyses will be necessary to unravel the molecular basis
      for cell type-specific splice site selection. This paper will highlight some
      recent progress and future challenges for functional genomics and bioinformatics
      in this rapidly developing area.

PMID- 15239894
TI  - ENU mutagenesis in the mouse: application to human genetic disease.
AB  - Genetic approaches in model organisms provide a powerful means by which to
      examine the biological basis of human diseases as well as the physiological
      processes that are affected by them. Although not without its drawbacks, the
      mouse has become the mammalian species of choice in studying the molecular basis
      of disease. Targeted mutagenesis approaches in the mouse have led to dramatic
      increases in our understanding of human disease processes. As a complement to
      these gene-driven studies, three developments have led to the reassessment of a
      phenotype-driven approach in the mouse--the accumulation of information that has
      emerged from human and mouse genome sequencing projects, the use of high
      efficiency point mutagens such as N-ethyl-N-nitrosourea (ENU) and the application
      of systematic hierarchical screening protocols for the mouse. In this paper,
      progress with existing phenotypic screening programmes is discussed and
      opportunities for the development of new mouse disease models are presented.

PMID- 15239895
TI  - Past, present and future strategies to study the genetics of body weight
      regulation.
AB  - Genetic advances have made remarkable progress towards our understanding of body
      weight regulation. Much of our current knowledge has come from the cloning and
      characterisation of the genes responsible for obesity syndromes in the mouse, and
      the identification of homologous mutations causing rare forms of obesity in
      humans. Gene targeting experiments in mice have been instrumental in confirming
      the importance of many genes in the aetiology of obesity, and the existence of a
      fundamental physiological pathway that controls energy balance is becoming clear.
      The genetic determinants that underlie common forms of human obesity are largely
      polygenic, with most genes producing small effects. Thus, elucidating the many
      genetic determinants of obesity is a current challenge for modern geneticists.
      Despite the inherent difficulties, progress has been made through
      linkage/association studies and a genetic map of quantitative trait loci for
      human obesity is beginning to emerge. Obesity research is now very much in a
      transition period. Not so long ago, access to high throughput screening, as well
      as microarray and proteomic techniques, was prohibitively expensive and available
      only to the few. In recent years, these technologies have become more accessible
      to the larger scientific community and, in this paper, we will discuss how such
      technological advances are likely to drive the next wave of progress in obesity
      research. For example, large-scale mutagenesis screens in rodents coupled with
      high throughput screening are likely to emerge as important technologies for
      identifying genes previously unexpected to be involved in body weight regulation.
      Furthermore, applications of microarray and proteomic techniques will further
      refine our understanding of currently known peptides as well as identify novel
      pathways and molecules which are involved in energy homeostasis.

PMID- 15239896
TI  - Utility of reverse phase protein arrays: applications to signalling pathways and
      human body arrays.
AB  - Protein microarrays offer a new means by which to conduct quantitative profiling
      of disease-associated proteins. The knowledge gained may provide novel strategies
      for early detection, diagnosis and therapeutic intervention. A variety of
      sophisticated approaches, including gene arrays, sequencing consortiums and large
      scale two-dimensional gel electrophoresis, continue to generate lists of proteins
      potentially linked to disease aetiology and progression. The challenge is to
      evaluate quantitatively promising lead protein candidates using matched normal
      and diseased cell populations. In contrast to the antibody array, the reverse
      phase protein microarrays (RPPA) do not require labelling of cellular protein
      lysates, and constitute a sensitive high throughput platform for marker
      screening, pathophysiology investigation and therapeutic monitoring. In this
      paper, examples will be provided using RPPAs in the study of the apoptotic
      signalling cascade and in the evaluation of the expression of organ-specific
      protein makers using microdissected human organ cell lysates configured as 'human
      body arrays'.

PMID- 15239897
TI  - There's no place like 'ome.

PMID- 15239898
TI  - The use of transgenic systems in pharmaceutical research.
AB  - Those pharmaceutical companies whose goal is to generate novel innovative drugs
      are faced with the challenge that only a fraction of the compounds tested in
      clinical trials eventually become a registered drug. This problem of attrition is
      compounded by the fact that the clinical trial or development stage is by far the
      most costly phase of bringing a new drug to market, consuming around 80 per cent
      of the total spend. Transgenic technology represents an attractive approach to
      reducing the attrition rate of compounds entering clinical trials by increasing
      the quality of the target and compound combinations making the transition from
      discovery into development. Transgenic technology can impact at many points in
      the discovery process, including target identification and target validation, and
      provides models designed to alert researchers early to potential problems with
      drug metabolism and toxicity, as well as providing better models for human
      diseases. In target identification, transgenic animals harbouring large DNA
      fragments can be used to narrow down genetic regions. Genetic studies often
      result in the identification of large genomic regions and one way to decrease the
      region size is to do complementation studies in transgenic animals using, for
      example, inserts from bacterial artificial chromosome (BAC) clones. In target
      validation, transgenic animals can be used for in vivo validation of a specific
      target. Considerable efforts are being made to establish new, rapid and robust
      tools with general utility for in vivo validation, but, so far, only transgenic
      animals work reliably on a wide range of targets. Transgenic animals can also be
      used to generate better disease models. Predictive animal models to test new
      compounds and targets will significantly speed up the drug discovery process and,
      more importantly, increase the quality of the compounds taken further in the
      research and development process. Humanised transgenic animals harbouring the
      human target molecule can be used to understand the effect of a compound acting
      on the human target in vivo. Also, models mimicking human drug metabolism will
      provide a means of assessing the effect of human-specific metabolites and of
      understanding the pharmacokinetic properties of potential drugs. In toxicology
      studies, transgenic animals are providing more predictive models. A good example
      of this are those models routinely used to look for carcinogenicity associated
      with new compounds.

PMID- 15239899
TI  - Progress towards cell-mediated gene transfer in zebrafish.
AB  - Although the zebrafish possesses several favourable characteristics that make it
      an ideal model for genetic studies of vertebrate development, one disadvantage of
      this model system is the absence of methods for the production of gene knockouts.
      The authors' laboratory, and others, are working to develop zebrafish pluripotent
      embryonic stem (ES) and primordial germ cell (PGC) cultures that can be used for
      cell-mediated gene transfer and the production of knockout mutant lines of fish.
      Progress has been made in developing short-term cell cultures that possess the
      ability to contribute to multiple tissues, including the germ line of a host
      embryo, and transgenic lines of zebrafish have been established using the embryo
      cell cultures. Work is in progress to extend the length of time that the embryo
      cells can be maintained in culture without losing their ability to generate germ
      line chimeras.

PMID- 15239900
TI  - High throughput genotyping technologies.
AB  - A comprehensive genetic map containing several hundred microsatellite markers
      resulted from a large microsatellite mapping project. This was the first real
      study that introduced high throughput methods to the genetic community. This map
      and the concurrent technological advances, which will briefly be reviewed, led to
      further numerous mapping investigations of simple and complex diseases. The
      annotated draft sequence of approximately three billion base pairs (bp) of the
      human genome has been completed much sooner than many imagined, due to
      considerable technological advancements and the international enterprise that
      resulted. This was a major development for the genetics community, but is only
      the precursor to the next phase of studying and understanding the variation
      within the human genome. The awareness of the differences may help us understand
      the effects on the genetics of the variation between individuals and disease. It
      is these variations at the nucleotide level that determine the physiological
      differences, or phenotypes of each individual, including all biological functions
      at the cellular and body level. Single nucleotide polymorphisms (SNPs) will
      provide the next high density map, and be the genetic tool to study these genetic
      variations. There are many sources of SNPs and exhaustive numbers of methods of
      SNP detection to be considered. The focus in this paper will be on the merits of
      selected, varied SNP typing methodologies that are emerging to genotype many
      individuals with the required huge number of SNPs to make the study of complex
      diseases and pharmacogenomics a practical and economically viable option.

PMID- 15239901
TI  - Activity-based probes for functional proteomics.
AB  - Achieving an understanding of the functional role of all proteins expressed by a
      complex organism will require the development of methods that enable the rapid
      monitoring of protein function on a global scale. Current genomics and proteomics
      technologies fall short of this goal since they measure only the relative
      abundance of transcripts and proteins, respectively. Recent efforts in several
      laboratories have led to the development of tagged chemical probes that
      selectively react with families of active enzymes based on shared mechanistic
      features. These activity-based probes (ABPs) permit the quantitation and
      comparison of multiple protein activities simultaneously in complex proteomes. In
      this paper, the general properties and design features of ABPs will be discussed
      with an emphasis on the use of ABPs for activity-based proteome analysis.

PMID- 15239902
TI  - Comparative mapping in farm animals.
AB  - This paper summarises the current status of comparative mapping in farm animals.
      For most of the major farm animal species, a wide range of genomic tools are now
      available to create high-resolution genetic and physical maps of the genome. For
      many farm animals, the use of radiation hybrid panels and sequence data from
      expressed sequence tag (EST) projects has accelerated the development of high
      resolution comparative maps, with human--the model species for farm animals.
      These tools and comparative maps are being used to map and identify the genes at
      the loci for simple and complex traits. The development of detailed physical maps
      in farm animals based on radiation hybrid panels and bacterial artificial
      chromosome (BAC) contigs provides a direct link between the 'information-poor'
      maps of farm animals and the 'information-rich' genomes of human and other model
      organisms.

PMID- 15239903
TI  - Expressing RNA aptamers inside cells to reveal proteome and ribonome function.
AB  - Small RNA molecules can participate in complex regulatory networks not merely
      through Watson-Crick interactions with other RNAs (as in anti-sense RNA), but
      also by forming discrete structures that bind protein or low-molecular weight
      targets. RNA aptamers derived from in vitro selections (SELEX) are being used
      inside cells for at least four purposes: (1) to antagonise normal cellular
      proteins as a means of elucidating their biological roles; (2) as decoys to
      natural RNA-binding proteins to reveal their functions or those of structural
      elements within naturally occurring transcripts; (3) as regulatory modules to
      govern the expression of exogenous genes; and (4) to antagonise disease-related
      targets for potential biomedical applications. This paper summarises recent
      advances in each of these areas, the parameters that influence successful
      application and the potential for future developments. The use of aptamers in
      vivo may serve as a paradigm for understanding how some non-coding RNAs and other
      elements of the ribonome exert their influence on the intracellular proteome, and
      is thus becoming an important tool for modern cell and molecular biology.

PMID- 15239904
TI  - Concepts in antibody phage display.
AB  - This paper introduces the reader to antibody phage display and its use in
      combinatorial biochemistry. The focus is on overviewing phage display formats,
      library design and selection technology, which are the prerequisites for the
      successful isolation of specific antibody fragments against a diverse set of
      target antigens.

PMID- 15239905
TI  - Ribosome display: cell-free protein display technology.
AB  - Ribosome display is a cell-free system for the in vitro selection of proteins and
      peptides from large libraries. It uses the principle of coupling individual
      nascent proteins (phenotypes) to their corresponding mRNA (genotypes), through
      the formation of stable protein-ribosome-mRNA (PRM) complexes. This permits the
      simultaneous isolation of a functional nascent protein, through affinity for a
      ligand, together with the encoding mRNA, which is then converted and amplified as
      DNA for further manipulation, including repeated cycles or protein expression.
      Ribosome display has a number of advantages over cell-based systems such as phage
      display; in particular, it can display very large libraries without the
      restriction of bacterial transformation. It is also suitable for generating
      toxic, proteolytically sensitive and unstable proteins, and allows the
      incorporation of modified amino acids at defined positions. In combination with
      polymerase chain reaction (PCR)-based methods, mutations can be introduced
      efficiently into the selected DNA pool in subsequent cycles, leading to
      continuous DNA diversification and protein selection (in vitro protein
      evolution). Both prokaryotic and eukaryotic ribosome display systems have been
      developed and each has its own distinctive features. In this paper, ribosome
      display systems and their application in selection and evolution of proteins are
      reviewed.

PMID- 15239907
TI  - Irritable bowel syndrome: management of expectations and disease.

PMID- 15239908
TI  - Chlamydia screening in primary care.

PMID- 15239909
TI  - Engaging with the public?

PMID- 15239910
TI  - Prevalence of irritable bowel syndrome: a community survey.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common health problem affecting a
      substantial proportion of the population. Many individuals with symptoms of IBS
      do not seek medical attention or have stopped consulting because of
      disillusionment with current treatment options. Such patients may choose to re
      consult with the advent of new therapies with a resulting impact on health
      services. AIM: To generate reliable estimates of the prevalence of IBS by age,
      sex and symptom group. DESIGN OF STUDY: Postal survey. SETTING: Patients selected
      from registers of eight general practices in north and west Birmingham. METHOD:
      Eight thousand six hundred and forty-six patients aged >or=18 years were randomly
      selected from practice lists. Selected patients received a questionnaire, which
      included diagnostic criteria for IBS. A second questionnaire, seeking more
      detailed information, was sent to those whose responses indicated the presence of
      IBS symptoms. RESULTS: Of the 8386 patients surveyed 4807 (57.3%) useable replies
      were received. The community-based prevalence of IBS was 10.5% (6.6% of men and
      14.0% of women). Overall the symptom profiles were characterised by diarrhoea
      (25.4%), constipation (24.1%) and alternating symptoms (46.7%). Over half (56%)
      of all patients had consulted their general practitioner within the past 6 months
      and 16% had seen a hospital specialist. A quarter of patients consulted more than
      twice and 16% were referred to secondary care; almost half were on prescribed
      medication. However, the majority of patients were self-treated. Less than half
      of those currently reporting symptoms of IBS according to the Rome II criteria
      had received a diagnosis of IBS. Reduced quality of life and a previous diagnosis
      of a stomach ulcer were identified as predictors of consultation. CONCLUSION:
      Quality of life was significantly reduced in patients with IBS. There is a
      substantial burden on primary healthcare services despite over half of those with
      symptoms also self- medicating. The Rome II diagnostic criteria identified those
      most affected by their symptoms and are a valid clinical tool. Population-based
      health surveys will need to supplement the Rome criteria with questions aiming to
      identify patients formally diagnosed but whose symptoms are currently under
      control if prevalence is to be reliably estimated.

PMID- 15239911
TI  - A comparison of irritable bowel syndrome patients managed in primary and
      secondary care: the Episode IBS study.
AB  - BACKGROUND: It is thought that people with irritable bowel syndrome (IBS) who
      consult secondary care have more severe symptomatology than those treated mainly
      in primary care. AIMS: To describe the physical and psychological symptoms of
      IBS, and the health-related quality of life of patients managed in primary and
      secondary care. DESIGN OF STUDY: Cross-sectional observational survey. SETTING:
      The general population of the United Kingdom (UK). METHODS: A cohort of people
      with IBS symptoms was recruited via a UK-wide newspaper advertisement. Frequency,
      duration and severity of symptoms, and health-related quality of life data were
      collected by semi-structured telephone interviews. Descriptive analysis allowed
      the comparison of those managed in primary care with those consulting secondary
      care. Logistic regression was used to identify factors associated with patients
      consulting secondary care. RESULTS: Data on 486 participants with confirmed IBS
      (Rome II criteria) were examined. Similar patterns in symptom severity were found
      in primary and secondary care groups. Factors associated with IBS patients
      consulting secondary care were: male sex, a longer length of time since
      diagnosis, having frequent bowel motions, not having dyspepsia in the past 3
      months, and having used medication and alternative therapies. Although patients
      managed in secondary care have greater impairment to their usual activities, both
      groups had similar health-related quality-of-life profiles. CONCLUSION: High
      levels of physical and psychological morbidity were present in population-based
      volunteers managed in both primary and secondary care. This study suggests that
      patients with IBS managed solely in primary care are affected as much as those
      attending secondary care.

PMID- 15239912
TI  - Barriers to opportunistic chlamydia testing in primary care.
AB  - BACKGROUND: Opportunistic testing and screening for genital chlamydia infection
      in sexually active women under the age of 25 years can lead to a reduction in
      chlamydia infection and its related morbidity. AIMS: To explore the barriers to
      testing for genital chlamydial infection in primary care. DESIGN OF STUDY:
      Qualitative study with focus groups. SETTING: Rural and urban general practice in
      Southwest England. METHODS: Focus groups were held with randomly selected high-
      and lowtesting general practices in Herefordshire, Gloucestershire and Avon. The
      high- and low-testing practices did not differ in their age/sex make-up, or by
      deprivation indices. Open questions were asked about the management of
      genitourinary symptoms and opportunistic testing for chlamydia. Data were
      collected and analysed concurrently until saturation occurred. RESULTS: Although
      staff from high test rate practices were much more aware of the evidence for
      opportunistic chlamydia testing and screening, none of the practices were happy
      to discuss chlamydia in a consultation unrelated to sexual health. The greatest
      barriers to opportunistic chlamydia testing and screening were lack of knowledge
      of the benefits of testing, when and how to take specimens, lack of time, worries
      about discussing sexual health, and lack of guidance. Healthcare staff stated
      that any increased testing should be accompanied by clear, concise primary care
      trust guidance on when and how to test, including how to obtain informed consent
      and perform contact tracing. Staff felt that testing could be undertaken at
      family planning clinics or with cervical smears if patients received information
      before the consultation. Alternatively, in larger practices specific chlamydia
      clinics could be held. CONCLUSION: The Department of Health needs to be aware of
      the extreme pressures that primary care staff are under, and the potential
      barriers to any screening implementation. Efforts to increase chlamydia screening
      in this setting should be accompanied by clear guidance and education. Any
      chlamydia clinics or increased testing must have appropriate financial and staff
      resources. Genitourinary medicine (GUM) clinics, or level three practices with
      GUM expertise, will need to be increased in parallel with testing in primary care
      to provide appropriate contact tracing and follow-up.

PMID- 15239913
TI  - Self-reported experiences of health services among female street-based
      prostitutes: a cross-sectional survey.
AB  - BACKGROUND: Previous studies show that women working in prostitution do not use
      routine health services appropriately. Little is known about the nature and
      frequency of service contacts or barriers to access. This information is needed
      if use of current services by this group is to improve. AIM: To identify barriers
      reducing access to health services by street prostitutes, and to identify current
      patterns of use. DESIGN OF STUDY: Cross-sectional survey. SETTING: Inner-city
      Bristol. METHOD: Seventy-one female street-based prostitutes were interviewed
      about their experiences of health services. RESULTS: The women had frequent
      contacts with healthcare providers. The general practitioner (GP) was the main
      source of all types of care. Although 83% (59/71) were registered with a GP, 62%
      (36/59) had not disclosed their work. Only 46% (33/71) had been screened for
      sexually transmitted infection in the previous year and 24% (17/71) were
      vaccinated against hepatitis B, a national recommendation for sex workers. Only
      38% (25/65) had had cervical smears according to screening guidelines.
      Opportunistic screening and care was important. While pregnant with their last
      child, only 30% (14/47) booked in the first trimester and attended all antenatal
      appointments, with 13% (6/47) receiving no antenatal care until admitted in
      labour. Appointments, waiting times, and fear of judgement and other patients
      staring, were considered significant barriers to service use. The model suggested
      by the women was an integrated service providing basic living needs alongside
      health care. CONCLUSION: Non-disclosure and poor attendance for follow-up make
      appropriate care difficult, and may contribute to poor health. Despite frequent
      service contacts, opportunities for care are being missed.

PMID- 15239914
TI  - Managing controversy through consultation: a qualitative study of communication
      and trust around MMR vaccination decisions.
AB  - BACKGROUND: Controversy over the measles, mumps, and rubella (MMR) vaccine has
      reduced uptake, raising concerns of a future disease epidemic. AIMS: To explore
      parents' accounts of decision making relating to the MMR vaccine controversy,
      identifying uptake determinants and education needs. DESIGN OF STUDY: Qualitative
      interviews analysed using the 'framework' approach. SETTING: Five general
      practices in the Leeds area, 2002-2003. METHOD: Sixty-nine interviews conducted
      with parents of children aged between 4 and 5 years, and 12 interviews with
      primary care practitioners, managers and immunisation coordinators serving
      participating sites. Participants were interviewed one-to-one in a place of their
      choice. RESULTS: The vaccination decision is primarily a function of parental
      assessments of the relative acceptability and likelihood of possible outcomes.
      For most parents the evidence of science and medicine plays little role in the
      decision. Although local general practitioners and health visitors are trusted
      information sources, the influence of primary care providers on the vaccination
      decision is limited by concerns over consultation legitimacy, discussion
      opportunity, and perceptions of financial and political partiality. Parents and
      practitioners identify a need for new approaches to support decisions and
      learning when faced with this and similar healthcare controversies. These include
      new collaborative approaches to information exchange designed to transform rather
      than supplant existing parent knowledge as part of an ongoing learning process.
      CONCLUSION: The study identified new ways in which parents and practitioners need
      to be supported in order to increase understanding of medical science and secure
      more informed decisions in the face of health controversy.

PMID- 15239915
TI  - Predicting uptake of MMR vaccination: a prospective questionnaire study.
AB  - BACKGROUND: Recent years have seen a decline in the uptake of the measles, mumps,
      and rubella (MMR) vaccination. AIM: To describe parents' beliefs about the MMR
      vaccination and to explore the best predictors of uptake by the age of 2 years.
      DESIGN OF STUDY: Prospective questionnaire study. SETTING: Brighton and Hove area
      of East Sussex. METHOD: Five hundred and eleven parents (response rate = 56.9%)
      completed a baseline questionnaire regarding their profile characteristics,
      beliefs about MMR and previous vaccination history prior to receiving a letter to
      attend for their child's vaccination. Attendance data was collected at follow-up
      by the age of 2 years. RESULTS: The majority of parents believed that measles,
      mumps and rubella were serious illnesses and stated that they would feel guilty
      about any adverse consequences of their decision about vaccination. Many
      responders were ambivalent about the benefit of vaccinations and were unsure
      whether to trust either the medical profession or the media. Uptake of MMR
      vaccination at follow-up was related to previous uptake for vaccination,
      increased faith in the medical profession, increased faith in the media, and a
      lower belief that vaccination is unhealthy and can harm the immune system.
      CONCLUSION: Many parents hold mixed beliefs about the MMR vaccination and the
      doctors who administer it. Uptake relates to past vaccination and more positive
      beliefs.

PMID- 15239917
TI  - Communicating about expected course and re-consultation for respiratory tract
      infections in children: an exploratory study.
AB  - Acute respiratory tract infection is the commonest reason for children
      consulting, and about one-fifth re-consult for the same illness episode. Fifty
      nine audiotape recordings from nine general practitioners (GPs) consulting with
      children with acute respiratory tract infections were examined. Prognosis was
      mentioned in only 22 consultations, with GPs predicting a brief course in 11, a
      possibly longer than expected course in six, and with predicted duration not made
      explicit in five. Carers were invited to re-consult if they were 'unhappy' with
      the child's condition in 11 consultations, and specific triggers to re-consult
      were provided in 15. A patient information leaflet was given out only once.
      Providing carers with an evidence-based account of the likely clinical course and
      communicating specific triggers to re-consult may help them manage more of these
      illness episodes without re-consulting.

PMID- 15239916
TI  - The prevention of type 2 diabetes: general practitioner and practice nurse
      opinions.
AB  - BACKGROUND: Primary prevention of type 2 diabetes is now possible with lifestyle
      or pharmacological interventions in people who are at risk. Primary care would
      seem to be the legitimate setting for this to take place. AIM: To explore the
      views of general practitioners and practice nurses about the detection and
      management of people at risk of developing type 2 diabetes. DESIGN OF STUDY:
      Qualitative study. SETTING: One local health board area in Wales. METHOD: General
      practitioners and practice nurses participated in multi-professional focus
      groups, and opinions of participants were analysed into themes and sub-themes
      according to focus group content analysis methodology to search for 'markers of
      text'. RESULTS: Participants from 21 practices were involved. Participants'
      opinions on the detection and management of individuals at risk of developing
      type 2 diabetes were polarised into those who considered these activities
      inappropriate for primary care and those who were already engaged in the
      detection, management and follow-up of these individuals. For the former,
      existing workload, the questionable role of primary care as a 'screening
      service', lack of resources, and conflict and concern about increasing
      specialisation were given as justification. Those already engaged in these
      activities emphasised their importance but were also concerned with the lack of
      available resources. Other concerns were the perceived low motivation of patients
      to modify their lifestyle and the unnecessary medicalisation of the precursor
      conditions of impaired glucose tolerance and impaired fasting glycaemia. The
      prevention of type 2 diabetes was seen as largely the responsibility of other
      agencies such as health promotion and education. CONCLUSION: The often strongly
      held views about this topic are at least partly influenced by current pressures
      on primary care. To make the primary prevention of type 2 diabetes a reality,
      either practitioners need to be motivated and resourced to carry out preventive
      strategies or alternative methods must be identified.

PMID- 15239921
TI  - Functional genomics and proteomics as a foundation for systems biology.
AB  - Developments in high-throughput measurement technologies for biological molecules
      have created a paradigm shift in modern life science research. The field of
      systems biology attempts to provide a systems-level understanding by
      systematically organising the genomic, functional genomic and proteomic data
      obtained from genetic and environmental perturbations of interest and using the
      data to build a descriptive and mechanistic model of the biological phenomena.
      The goal is to build a mathematical framework with some predictive abilities.
      This review highlights the need for system-level understanding, lists some of the
      high-throughput measurement tools of importance in systems biology, reviews
      various types of experimental and computational approaches being used in systems
      biology research and attempts to address some of the challenges facing this
      research community.

PMID- 15239922
TI  - Application of proteomics for discovery of protein biomarkers.
AB  - Biomarkers of drug efficacy and toxicity are becoming a key need in the drug
      development process. Mass spectral-based proteomic technologies are ideally
      suited for the discovery of protein biomarkers in the absence of any prior
      knowledge of quantitative changes in protein levels. The success of any biomarker
      discovery effort will depend upon the quality of samples analysed, the ability to
      generate quantitative information on relative protein levels and the ability to
      readily interpret the data generated. This review will focus on the strengths and
      weaknesses of technologies currently utilised to address these issues.

PMID- 15239918
TI  - Respiratory medicine.
AB  - The General Medical Services (GMS) contract has focused the attention of United
      Kingdom (UK) general practitioners (GPs) on the provision of high quality routine
      care for patients with chronic disease. The quality markers defined by the
      contract endorse the need for objective diagnosis and structured care recommended
      by the British Thoracic Society/Scottish Intercollegiate Guideline Network (BTS
      SIGN) guideline for the management of asthma and the National Institute for
      Clinical Excellence (NICE) guideline on the management of chronic obstructive
      pulmonary disease (COPD). In this paper the key recommendations of these
      guidelines and their implementation in the pragmatic world of general practice
      are discussed, with specific focus on diagnosis, monitoring, management, self
      management and delivery of care.

PMID- 15239923
TI  - Detection of renal cell carcinoma-associated markers via proteome- and other
      'ome'-based analyses.
AB  - Proteome analysis has rapidly developed in the post-genome era and is now widely
      accepted as the complementary technology for genetic profiling. It has been shown
      to be a powerful tool for studying human diseases and for identifying novel
      prognostic, diagnostic and therapeutic markers. This review focuses on the
      identification of new biomarkers and therapeutic targets for renal cell carcinoma
      using different 'ome'-based technologies.

PMID- 15239924
TI  - Genomic analysis of facioscapulohumeral muscular dystrophy.
AB  - The genomic basis of facioscapulohumeral muscular dystrophy (FSHD) is of
      considerable interest because of the unique nature of the molecular mutation,
      which is a deletion within a large, complex DNA tandem array (D4Z4). This repeat
      maps within 30 kb of the 4q telomere. Although D4Z4 repeat units each contain an
      open reading frame that could encode a homeodomain protein, there is no evidence
      that the repeat is transcribed, and the underlying disease mechanism probably
      involves a position effect. A recent study has identified a protein complex bound
      to D4Z4 that contains YY1 and HMGB2, implicating a role for D4Z4 as a repressor.
      The 4q telomere has two variants, 4qA and 4qB. Although these alleles are present
      at almost equal frequencies in the general population, FSHD is associated only
      with the 4qA allele and never with 4qB. This suggests a functional difference
      between the telomere variants, either in predisposition to deletions within D4Z4
      or in the pathological consequence of the deletion. Comparative mapping studies
      of the FSHD region in primates, mouse and Fugu rubripes have given insights into
      the evolutionary history of the D4Z4 repeat and of 4qter, although as yet they
      have not provided any solutions to the FSHD puzzle.

PMID- 15239925
TI  - The comparative genomics of T-box genes.
AB  - T-box genes are defined by the presence of a conserved sequence, the so-called T
      box; this codes for the T-domain, which is involved in DNA-binding and protein
      dimerisation. Members of this gene family have been found in all metazoans, from
      diploblasts to humans, and mutations in T-box gene family members in humans have
      been linked to several congenital disorders. Sequencing of the complete genomes
      of a range of invertebrate and vertebrate species has allowed the classification
      of individual T-box genes into five subfamilies: Brachyury, T-brain1, Tbx1, Tbx2
      and Tbx6. This review will largely focus on T-box genes identified in organisms
      whose genomes have been fully sequenced, emphasising how comparative studies of
      the T-box gene family will help to reveal the roles of these genes during
      development and in the adult.

PMID- 15239926
TI  - Global effects of histone modifications.
AB  - The relationship between chromatin structure and transcriptional regulation has
      been the focus of many research publications over the past few years. A lot of
      progress has been made in understanding the role of histone modifications. The
      interdependence of histone methylation and DNA methylation has been revealed.
      Methylation, acetylation, phosphorylation and ubiquitination of specific histone
      residues are all able to affect the DNA binding of transcription factors and to
      change the structure of chromatin on a genome-wide scale. This review aims to
      summarise some of the experiments that demonstrated the global effects of the
      modifications of the five histone proteins, H1, H2A, H2B, H3 and H4.

PMID- 15239927
TI  - Baculovirus display strategies: Emerging tools for eukaryotic libraries and gene
      delivery.
AB  - Recombinant baculoviruses have been extensively used as vectors for abundant
      expression of a large variety of foreign proteins in insect cell cultures. The
      appeal of the system lies essentially in easy cloning techniques and virus
      propagation combined with the eukaryotic post-translational modification
      machinery of the insect cell. Recently, a novel molecular biology tool was
      established by the development of baculovirus surface display, using different
      strategies for presentation of foreign peptides and proteins on the surface of
      budded virions. This eukaryotic display system enables presentation of large
      complex proteins on the surface of baculovirus particles and has thereby become a
      versatile system in molecular biology. Surface display strategies play an
      important role, as they may be used to enhance the efficiency and specificity of
      viral binding and entry to mammalian cells. In addition, baculovirus surface
      display vectors have been engineered to contain mammalian promoter elements
      designed for gene delivery both in vitro and in vivo. Moreover, baculovirus
      capsid display has recently been developed; this holds promise for intracellular
      targeting of the viral capsid and subsequent cytosolic delivery of desired
      protein moieties. Finally, the viruses can accommodate large insertions of
      foreign DNA and replicate only in insect cells. Together, these are attributes
      that are very likely to make them important tools in functional genomics and
      proteomics.

PMID- 15239928
TI  - PROCEED: A proteomic method for analysing plasma membrane proteins in living
      mammalian cells.
AB  - Elucidating the profile of extracellular integral membrane proteins on live cells
      is vital for uncovering diagnostic disease biomarkers, therapeutic agents and
      drug receptor candidates. Exploring the realm of these proteins has proved to be
      an intricate task, mainly due to their hydrophobic nature and low abundance.
      Furthermore, the level of purity achieved by classical methods of purification
      and cell fractionation is insufficient. These restrictions pose major limitations
      for gel electrophoresis or chromatography-based separation techniques as the
      preferred methodologies for high-throughput analysis. Mass spectrometry has
      alleviated most of the difficulties in the identification of proteins in general;
      however, the Achilles' heel is still the isolation and separation of membrane
      proteins. In order to circumvent these limitations, a high-throughput platform
      has been devised, whereby proteases are applied to whole intact living cells. The
      resulting peptide fragments are then analysed by liquid chromatology followed by
      tandem MS (LC-MS/MS) technology to provide a detailed profile of proteins exposed
      on the surface of the plasma membrane. This kind of protein trimming offers the
      advantages that no prior manipulation or fractionation of the cell is required,
      contaminating proteins are remarkably reduced and the procedure is adequate for
      high-throughput purposes. This method, referred to as PROCEED (PROteome of Cell
      Exposed Extracellular Domains) is compatible with isotope labelling techniques
      which facilitate comparative protein expression studies. The methodology is
      extendable to all cell types including yeast and bacteria. Finally, the
      advantages and the limitations of PROCEED are discussed in view of other current
      technologies.

PMID- 15239929
TI  - The Drosophila genome: the way forward.

PMID- 15239930
TI  - Drosophila microarray platforms.
AB  - The advent of high throughput microarrays and the complete sequencing of the
      Drosophila melanogaster genome have enabled global gene expression analysis in
      this powerful genetic model organism. Currently, researchers are using three main
      Drosophila array platform types, with elements composed of cDNA amplicons,
      oligonucleotides (short and long) or genomic amplicons. This paper provides a
      broad overview of these platforms.

PMID- 15239931
TI  - Proteomics in Drosophila melanogaster.
AB  - To be able to understand cellular mechanisms, we require fully integrated data
      sets combining information about gene expression, protein expression, post
      translational modification states, sub-cellular location and complex formation.
      Proteomics is a very powerful technique that can be applied to interrogate
      changes at the protein level. Studying this effectively requires specialised
      facilities within research institutes. Here, we describe the setting up and
      operation of such a facility, providing a resource for the Arabidopsis and
      Drosophila research communities.

PMID- 15239932
TI  - Peptidomics in Drosophila melanogaster.
AB  - In analogy with proteomics technology, where all proteins expressed in a cell or
      tissue are analysed, the peptidomic approach aims at the simultaneous
      visualisation and identification of the whole peptidome of a cell or tissue, ie
      all expressed peptides with their post-translational modifications. With
      nanoscale liquid chromatography (nanoLC), combined with mass spectrometry and
      subsequent database searching, the peptidome of the Drosophila larval brain has
      been identified at the amino acid sequence level. In a single experiment
      involving only 50 Drosophila larval brains, one can obtain a display of the
      expressed peptides. In this paper, current peptidomics technology will be
      explained, using Drosophila as an example. Compared with the 400,000 Drosophila
      whole bodies that were required as a starting material for traditional
      biochemical peptide purification rounds, the authors are convinced that
      peptidomics technology, which in the future will certainly be applied to the
      analysis of different physiological states, has the inherent potential to bring
      about a true revolution in the study of the molecular physiology of Drosophila.

PMID- 15239933
TI  - The Drosophila phenotype gap - and how to close it.
AB  - Functional genomics (the elucidation of gene function in the context of a
      sequenced genome) depends critically on functional biology. Genetic model
      organisms have hitherto not attracted much physiological input, however. This
      skills mismatch, termed the phenotype gap, can be quantified by analysis of the
      annotations of sequenced genomes. This is illustrated in the context of
      Drosophila. In this case, it seems as if a shift from developmental biology to
      transport physiology and metabolism will be required to provide a more balanced
      skills base for post-genomics.

PMID- 15239934
TI  - The Drosophila melanogaster genome sequencing and annotation projects: a status
      report.
AB  - The sequence and genome annotations of Drosophila melanogaster were initially
      published in late 1999 and early 2000. Since then, the Berkeley Drosophila Genome
      Project (BDGP) and FlyBase have improved the quality of the sequence and reviewed
      the annotations by hand, respectively, to produce an account of the fruit fly
      genome that is of the highest quality. This review discusses the main features of
      this process, both from the point of view of the biology revealed in the end
      result and in the development of software that has been central to this genome
      sequencing and annotation project.

PMID- 15239935
TI  - In vivo protein trapping in Drosophila.
AB  - The deciphering of complete genome sequences has opened a post-genomic proteomics
      era. While the sequence of many proteins is now known, attention will
      increasingly focus on the complex interaction networks that regulate their
      activity, and the analysis of protein distribution in the cell will be crucial to
      elucidating their function. A new generation of gene trapping devices, protein
      trap transposons, offers a way of analysing In vivo the dynamics of sub-cellular
      distribution of a large number of proteins. Many transgenic lines have already
      been established and are available. Screens focusing on particular cell
      compartments can be devised.

PMID- 15239936
TI  - Genome manipulation by homologous recombination in Drosophila.
AB  - By utilising a cell's recombinational machinery, researchers in many different
      model organisms have been able to perform gene targeting experiments in which
      specific sequence alterations are introduced into virtually any endogenous gene.
      Not only can functional knock-outs be generated by gene targeting, interesting
      alleles with mutations encoding specific amino acid replacements can also be
      made. A practical gene targeting method has only recently become available for
      Drosophila. This article reviews the Drosophila gene targeting method, with
      emphases placed on different approaches that are being used to generate different
      mutations.

PMID- 15239937
TI  - Proteomic profiling of cancer biomarkers.
AB  - Early detection and correct diagnosis are essential for effective treatment of
      cancer and patient survival. Complete sequencing of the human genome, and the
      genomes of other species, provides valuable tools for discerning the genetic
      abnormalities in cancer. However, differences between cancerous and normal cells
      reflect more than variations in genetic sequences and abundance of transcribed
      RNA. Many cancer biomarkers are manifestation of differences in post
      transcriptional splicing and/or post-translational modifications. Thus, proteomic
      tools are being increasingly utilised in the post-genomic era for discovery of
      new cancer biomarkers. In this paper we will provide an overview of the biomarker
      discovery process from the proteomic profiling point of view, with emphasis given
      to the principles that are involved in the process, including the protein
      identification strategies, and how surface enhanced laser desorption ionisation
      mass spectrometry fits into the picture. The aim is to provide a resource for the
      experimental practitioner seeking awareness of the analytical tools that are now
      available in contemporary cancer research.

PMID- 15239938
TI  - Platform technologies for microarray analysis.

PMID- 15239939
TI  - Resource and hardware options for microarray-based experimentation.
AB  - DNA microarray technology permits the study of biological systems and processes
      on a genome-wide scale. Arrays based on cDNA clones, oligonucleotides and genomic
      clones have been developed for investigations of gene expression, genetic
      analysis and genomic changes associated with disease. Over the past 3-4 years,
      microarrays have become more widely available to the research community. This has
      occurred through increased commercial availability of custom and generic arrays
      and the development of robotic equipment that has enabled array printing and
      analysis facilities to be established in academic research institutions. This
      brief review examines the public and commercial resources, the microarray
      fabrication and data capture and analysis equipment currently available to the
      user.

PMID- 15239940
TI  - Advances in spotted microarray resources for expression profiling.
AB  - The new millennium has ushered in a new era in human biology. The elucidation of
      the human genome sequence, together with those of model organisms, provides us
      with an unprecedented insight into the makeup of our genetic blueprint. The
      challenge now is to figure out how all the constituent pieces fit together to
      form the whole picture, and the consequences of what happens when the process
      goes awry. One experimental tool that has the potential to provide enormous
      insights into this complex process is expression profiling using microarrays. The
      past few years have seen a considerable growth in the availability and use of
      microarrays. Fuelled in part by the many genome projects currently underway,
      there has been a large increase in the number of organisms for which microarray
      reagents are available from both commercial and academic sources. In addition to
      the increasing number of genome-wide probe sets that are available, a significant
      amount of attention has been focussed on generating more targeted probe sets that
      focus in on specific pathways or biological processes. Finally, the microarray
      field is starting to see a shift away from the use of cDNAs or polymerase chain
      reaction (PCR) products as probes towards the use of 50-70mer oligonucleotide
      probes with all of the potential advantages that they offer. The aim of this
      review is to provide an overview of what is currently available in terms of
      spotted microarray reagents both with respect to pre-made arrays and to probe
      sets available for arraying.

PMID- 15239941
TI  - Strategies for microarray analysis of limiting amounts of RNA.
AB  - One of the critical limitations of current microarray technologies for use in
      expression analyses is the relatively large amount of input RNA required to
      generate labelled cDNA populations for array analysis. In situations where RNA is
      limiting, the options for expression profiling are to increase cDNA labelling and
      hybridisation efficiency, or to use an amplification strategy to generate enough
      RNA/cDNA for use with a standard labelling method. Sample amplification
      approaches must preserve the representation of the relative abundances of the
      different RNAs within the starting population and must also be highly
      reproducible. This review evaluates current signal and sample amplification
      technologies, including those that can be used to generate labelled cDNA
      populations for array analysis from as little as a single cell.

PMID- 15239942
TI  - Current status and future prospects of array-based comparative genomic
      hybridisation.
AB  - The majority of human cancers as well as many developmental abnormalities harbour
      chromosomal imbalances, many of which result in the gain and/or loss of genomic
      material. Conventional comparative genomic hybridisation (CGH) has been used
      extensively to map DNA copy number changes to chromosomal positions. The
      introduction of microarray CGH provided a powerful tool to precisely detect and
      quantify genomic aberrations and map these directly onto the sequence of the
      human genome. In the past several years, a number of different approaches towards
      array-based CGH have been undertaken. This paper reviews these approaches and
      presents some of the recently-developed applications of this new technology in
      both research and clinical settings.

PMID- 15239943
TI  - Beyond expression profiling: next generation uses of high density oligonucleotide
      arrays.
AB  - In the past decade, microarray technology has become a major tool for high
      throughput comprehensive analysis of gene expression, genotyping and resequencing
      applications. Currently, the most widely employed application of high-density
      oligonucleotide arrays (HDOAs) involves monitoring changes in gene expression.
      This application has been carried out in a variety of organisms ranging from
      Escherichia coli to humans. The recent near completion of the human and mouse
      genome sequences, however, as well as the genomes of other model experimental
      species, has allowed for novel applications of HDOAs, such as: the discovery of
      novel transcripts, mapping functionally important genomic regions and identifying
      functional domains in RNA molecules. Integrating all this information will
      provide novel global views of the locations of RNA transcription, DNA replication
      and the protein nucleic acid interactions that regulate these processes.

PMID- 15239944
TI  - Transposable elements as tools for genomics and genetics in Drosophila.
AB  - The P-element has been the workhorse of Drosophila genetics since it was
      developed as a tool for transgenesis in 1982; the subsequent development of a
      variety of systems based on the transposon have provided a range of powerful and
      flexible tools for genetics and genomics applications. P-element insertions are
      frequently used as starting-points for generating chromosomal deletions to remove
      flanking genes, either by screening for imprecise excision events or by selecting
      for male recombination events. Elements that utilise the yeast FLP/FLP
      recombination target (FRT) site-specific recombination system have been widely
      used to generate molecularly marked mitotic clones for mosaic analysis, extending
      the reach of this powerful genetic tool to virtually all areas of developmental
      biology. P-elements are still widely used as traditional mutagenesis reagents and
      form the backbone of projects aimed at generating insertions in every predicted
      gene in the fly genome. In addition, vectors based on the FLP/FRT system are
      being used for genome-wide applications, including the development of molecularly
      mapped deletion and duplication kits. In addition to these 'traditional' genetic
      approaches, a variety of engineered elements have been developed for a wide range
      of transgenic applications, including enhancer trapping, gene-tagging, targeted
      misexpression, RNA interference (RNAi) delivery and homologous recombination/gene
      replacement. To complement the use of P-elements, alternative transposon vectors
      have been developed. The most widely used of these are the lepidopteran element
      piggyBac and a Drosophila hydei transposon, Minos. In total, a range of
      transposon vectors offers the Drosophila biologist considerable flexibility and
      sophistication in manipulating the genome of the fly and has allowed rapid
      advances in all areas of developmental biology and genome science.

PMID- 15239945
TI  - Semaphorins guide PerPlexeD endothelial cells.
AB  - Abrogation of the endothelial cell-specific semaphorin receptor PlexinD1 in
      zebrafish and mouse reveals semaphorin functions selectively affecting the
      cardiovascular system. Neuropilins team up with PlexinD1 to form a novel
      endothelial receptor complex for class 3 semaphorins.

PMID- 15239946
TI  - More than cell death: caspases and caspase inhibitors on the move.
AB  - It is becoming clear that "apoptotic" caspases can effect cellular processes
      other than cell death. A recent paper in Cell points to a novel role of the
      Drosophila caspase inhibitor DIAP1 as a determinant of cell migration.

PMID- 15239947
TI  - Making tubes: step by step.
AB  - Branched hollow tubes form the architectural basis of many mammalian organs. The
      growth factor HGF/SF and its receptor, the Met receptor tyrosine kinase,
      stimulate epithelial cells to undergo tubulogenesis in vitro. In this issue of
      Developmental Cell, O'Brien et al. (2004) look at temporal regulation and the
      role of two HGF/SF effectors, the ERK 1/2 MAP kinases and matrix
      metalloproteases, in this process.

PMID- 15239948
TI  - Thirteen is the lucky number for doublecortin.
AB  - Doublecortin is a microtubule-associated protein that is essential for normal
      brain development. A recent report published in Molecular Cell shows that
      doublecortin associates preferentially with microtubules made of 13
      protofilaments, by recognizing a novel site between the protofilaments. These
      findings explain how doublecortin stabilizes microtubules and provide clues about
      its function during neuronal migration.

PMID- 15239949
TI  - h-ERES-y in ER-Golgi transport.
AB  - A debate continues over whether the Golgi is a stable organelle or a transient
      manifestation of continuous membrane flow from specialized ER exit domains
      (ERES). A new study from daSilva and colleagues shows that in plant cells,
      individual Golgi always form adjacent to an existing ERES, and that an ERES and
      its associated Golgi stack move as a single secretory unit. Their results support
      a model in which Golgi biogenesis correlates with ERES function.

PMID- 15239950
TI  - Muscle building; mechanisms of myotube guidance and attachment site selection.
AB  - The complex muscle patterns of higher organisms arise as migrating myoblasts are
      guided toward and connect with specific attachment sites. We review here the
      current understanding of myotube migration, focusing on its dynamic nature and
      the few molecular cues that have been identified to date. Much of this knowledge
      comes from studies in Drosophila, where powerful methods for in vivo imaging and
      genetic manipulation can be used to tackle this important but largely unsolved
      problem in developmental biology.

PMID- 15239951
TI  - ERK and MMPs sequentially regulate distinct stages of epithelial tubule
      development.
AB  - Epithelial cells undergo tubulogenesis in response to morphogens such as
      hepatocyte growth factor (HGF). To organize into tubules, cells must execute a
      complex series of morphogenetic events; however, the mechanisms that underlie the
      timing and sequence of these events are poorly understood. Here, we show that
      downstream effectors of HGF coordinately regulate successive stages of
      tubulogenesis. Activation of extracellular-regulated kinase (ERK) is necessary
      and sufficient for the initial stage, during which cells depolarize and migrate.
      ERK becomes dispensable for the latter stage, during which cells repolarize and
      differentiate. Conversely, the activity of matrix metalloproteases (MMPs) is
      essential for the late stage but not the initial stage. Thus, ERK and MMPs define
      two regulatory subprograms that act in sequence. By inducing these reciprocal
      signals, HGF directs the morphogenetic progression of tubule development.

PMID- 15239952
TI  - Sef is a spatial regulator for Ras/MAP kinase signaling.
AB  - Spatiotemporal control of the Ras/ERK MAP kinase signaling pathway is among the
      key mechanisms for regulating a wide variety of cellular processes. In this
      study, we report that human Sef (hSef), a recently identified inhibitor whose
      action mechanism has not been fully defined, acts as a molecular switch for ERK
      signaling by specifically blocking ERK nuclear translocation without inhibiting
      its activity in the cytoplasm. Thus, hSef binds to activated forms of MEK,
      inhibits the dissociation of the MEK-ERK complex, and blocks nuclear
      translocation of activated ERK. Consequently, hSef inhibits phosphorylation and
      activation of the nuclear ERK substrate Elk-1, while it does not affect
      phosphorylation of the cytoplasmic ERK substrate RSK2. Downregulation of
      endogenous hSef by hSef siRNA enhances the stimulus-induced ERK nuclear
      translocation and the activity of Elk-1. These results thus demonstrate that hSef
      acts as a spatial regulator for ERK signaling by targeting ERK to the cytoplasm.

PMID- 15239953
TI  - Timing and checkpoints in the regulation of mitotic progression.
AB  - Accurate chromosome segregation relies on the precise regulation of mitotic
      progression. Regulation involves control over the timing of mitosis and a spindle
      assembly checkpoint that links anaphase onset to the completion of chromosome
      microtubule attachment. In this paper, we combine live-cell imaging of HeLa cells
      and protein depletion by RNA interference to examine the functions of the Mad,
      Bub, and kinetochore proteins in mitotic timing and checkpoint control. We show
      that the depletion of any one of these proteins abolishes the mitotic arrest
      provoked by depolymerizing microtubules or blocking chromosome-microtubule
      attachment with RNAi. However, the normal progress of mitosis is accelerated only
      when Mad2 or BubR1, but not other Mad and Bub proteins, are inactivated.
      Moreover, whereas checkpoint control requires kinetochores, the regulation of
      mitotic timing by Mad2 and BubR1 is kinetochore-independent in fashion. We
      propose that cytosolic Mad2-BubR1 is essential to restrain anaphase onset early
      in mitosis when kinetochores are still assembling.

PMID- 15239954
TI  - The mitochondrial morphology protein Mdm10 functions in assembly of the
      preprotein translocase of the outer membrane.
AB  - The biogenesis of mitochondrial outer membrane proteins involves the general
      translocase of the outer membrane (TOM complex) and the sorting and assembly
      machinery (SAM complex). The two known subunits of the SAM complex, Mas37 and
      Sam50, are required for assembly of the abundant outer membrane proteins porin
      and Tom40. We have identified an unexpected subunit of the SAM complex, Mdm10,
      which is involved in maintenance of mitochondrial morphology. Mitochondria
      lacking Mdm10 are selectively impaired in the final steps of the assembly pathway
      of Tom40, including the association of Tom40 with the receptor Tom22 and small
      Tom proteins, while the biogenesis of porin is not affected. Yeast mutants of
      TOM40, MAS37, and SAM50 also show aberrant mitochondrial morphology. We conclude
      that Mdm10 plays a specific role in the biogenesis of the TOM complex, indicating
      a connection between the mitochondrial protein assembly apparatus and the
      machinery for maintenance of mitochondrial morphology.

PMID- 15239955
TI  - The PDGF/VEGF receptor controls blood cell survival in Drosophila.
AB  - The Drosophila PDGF/VEGF receptor (PVR) has known functions in the guidance of
      cell migration. We now demonstrate that during embryonic hematopoiesis, PVR has a
      role in the control of antiapoptotic cell survival. In Pvr mutants, a large
      fraction of the embryonic hemocyte population undergoes apoptosis, and the
      remaining blood cells cannibalistically phagocytose their dying peers.
      Consequently, total hemocyte numbers drop dramatically during embryogenesis, and
      large aggregates of engorged macrophages carrying multiple apoptotic corpses
      form. Hemocyte-specific expression of the pan-caspase inhibitor p35 in Pvr
      mutants eliminates hemocyte aggregates and restores blood cell counts and
      morphology. Additional rescue experiments suggest involvement of the Ras pathway
      in PVR-mediated blood cell survival. In cell culture, we demonstrate that PVR
      directly controls survival of a hemocyte cell line. This function of PVR shows
      striking conservation with mammalian hematopoiesis and establishes Drosophila as
      a model to study hematopoietic cell survival in development and disease.

PMID- 15239956
TI  - Evidence for tension-based regulation of Drosophila MAL and SRF during invasive
      cell migration.
AB  - Cells migrating through a tissue exert force via their cytoskeleton and are
      themselves subject to tension, but the effects of physical forces on cell
      behavior in vivo are poorly understood. Border cell migration during Drosophila
      oogenesis is a useful model for invasive cell movement. We report that this
      migration requires the activity of the transcriptional factor serum response
      factor (SRF) and its cofactor MAL-D and present evidence that nuclear
      accumulation of MAL-D is induced by cell stretching. Border cells that cannot
      migrate lack nuclear MAL-D but can accumulate it if they are pulled by other
      migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous,
      which affects actin dynamics. MAL-D/SRF activity is required to build a robust
      actin cytoskeleton in the migrating cells; mutant cells break apart when
      initiating migration. Thus, tension-induced MAL-D activity may provide a feedback
      mechanism for enhancing cytoskeletal strength during invasive migration.

PMID- 15239957
TI  - Xenopus XsalF: anterior neuroectodermal specification by attenuating cellular
      responsiveness to Wnt signaling.
AB  - Here we show that XsalF, a frog homolog of the Drosophila homeotic selector
      spalt, plays an essential role for the forebrain/midbrain determination in
      Xenopus. XsalF overexpression expands the domain of forebrain/midbrain genes and
      suppresses midbrain/hindbrain boundary (MHB) markers and anterior hindbrain
      genes. Loss-of-function studies show that XsalF is essential for the expression
      of the forebrain/midbrain genes and for the repression of the caudal genes.
      Interestingly, XsalF functions by antagonizing canonical Wnt signaling, which
      promotes caudalization of neural tissues. XsalF is required for anterior-specific
      expressions of GSK3beta and Tcf3, genes encoding antagonistic effectors of Wnt
      signaling. Loss-of-function phenotypes of GSK3beta and Tcf3 mimic those of XsalF
      while injections of GSK3beta and Tcf3 rescue loss-of-function phenotypes of
      XsalF. These findings suggest that the forebrain/midbrain-specific gene XsalF
      negatively controls cellular responsiveness to posteriorizing Wnt signals by
      regulating region-specific GSK3beta and Tcf3 expression.

PMID- 15239958
TI  - PlexinD1 and semaphorin signaling are required in endothelial cells for
      cardiovascular development.
AB  - The identification of new signaling pathways critical for cardiac morphogenesis
      will contribute to our understanding of congenital heart disease (CHD), which
      remains a leading cause of mortality in newborn children worldwide. Signals
      mediated by semaphorin ligands and plexin receptors contribute to the intricate
      patterning of axons in the central nervous system. Here, we describe a related
      signaling pathway involving secreted class 3 semaphorins, neuropilins, and a
      plexin receptor, PlexinD1, expressed by endothelial cells. Interruption of this
      pathway in mice results in CHD and vascular patterning defects. The type of CHD
      caused by inactivation of PlexinD1 has previously been attributed to
      abnormalities of neural crest. Here, we show that this form of CHD can be caused
      by cell-autonomous endothelial defects. Thus, molecular programs that mediate
      axon guidance in the central nervous system also function in endothelial cells to
      orchestrate critical aspects of cardiac morphogenesis.

PMID- 15239959
TI  - Semaphorin-plexin signaling guides patterning of the developing vasculature.
AB  - Major vessels of the vertebrate circulatory system display evolutionarily
      conserved and reproducible anatomy, but the cues guiding this stereotypic
      patterning remain obscure. In the nervous system, axonal pathways are shaped by
      repulsive cues provided by ligands of the semaphorin family that are sensed by
      migrating neuronal growth cones through plexin receptors. We show that proper
      blood vessel pathfinding requires the endothelial receptor PlexinD1 and
      semaphorin signals, and we identify mutations in plexinD1 in the zebrafish
      vascular patterning mutant out of bounds. These results reveal the fundamental
      conservation of repulsive patterning mechanisms between axonal migration in the
      central nervous system and vascular endothelium during angiogenesis.

PMID- 15239960
TI  - Localization-dependent oskar protein accumulation; control after the initiation
      of translation.
AB  - The appearance of Oskar protein occurs coincident with localization of oskar mRNA
      to the posterior pole of the Drosophila oocyte, and earlier accumulation of the
      protein is prevented by translational repression. We find that the nascent
      polypeptide-associated complex (NAC) is required for correct localization of
      oskar mRNA. The timing of the defects suggests that, if NAC acts directly via an
      interaction with nascent Oskar protein, oskar mRNA should be undergoing
      translation prior to its localization. Polysome analysis confirms that oskar mRNA
      is associated with polysomes even in the absence of localization of the mRNA or
      accumulation of Oskar protein. Thus, the mechanisms that prevent accumulation of
      Oskar protein until it can be secured at the posterior pole of the oocyte include
      regulated degradation or inhibition of translational elongation.

PMID- 15239962
TI  - Effects of iron-chelators on ion-channels and HIF-1alpha in the carotid body.
AB  - Acute hypoxia instantaneously increases the chemosensory discharge from the
      carotid body, increasing ventilation mostly by inhibiting the oxygen sensitive
      ion channels and exciting the mitochondrial functions in the glomus cells. On the
      other hand, Fe2+-chelation mimics hypoxia by inhibiting the prolyl hydroxylases
      and the degradation of HIF-1alpha in non-excitable cells. Whether Fe2+-chelation
      can inhibit the ion channels giving rise to the sensory responses in excitable
      cells was the question. We characterized the responses to Fe2+-chelators on
      excitable glomus cells of the rat, and found that they instantaneously blocked
      the ion-channels, exciting the chemosensory discharge, and later causing a
      gradual accumulation of HIF-1alpha. Although initiated by the same stimuli, the
      two effects (on ion channels and cytosolic HIF-1alpha) possibly occurred by two
      different mechanisms.

PMID- 15239961
TI  - A transposon-mediated gene trap approach identifies developmentally regulated
      genes in zebrafish.
AB  - We report here development of a novel gene trap method in zebrafish using the
      Tol2 transposon system. First, we established a highly efficient transgenesis
      method in which a plasmid DNA containing the Tol2 transposon vector and the
      transposase mRNA synthesized in vitro were coinjected into one-cell stage
      embryos. The transposon vector inserted in the genome could be transmitted to the
      F1 progeny at high frequencies, and regulated gene expression by a specific
      promoter could be recapitulated in transgenic fish. Then we constructed a
      transposon-based gene trap vector containing a splice acceptor and the GFP gene,
      performed a pilot screen for gene trapping, and obtained fish expressing GFP in
      temporally and spatially restricted patterns. We confirmed the endogenous
      transcripts were indeed trapped by the insertions, and the insertion could
      interfere with expression of the trapped gene. We propose our gene trap approach
      should facilitate studies of vertebrate development and organogenesis.

PMID- 15239964
TI  - Arterial chemoreceptors in the superior laryngeal nerve of the rat.
AB  - Paraganglia resembling the carotid body have been described in the superior
      laryngeal nerve (SLN) of the rat and the aim of the present study was to
      determine if this tissue is chemosensitive. We developed a novel isolated SLN
      preparation superfused with HEPES-buffered Tyrode solution at 35 degrees C in
      vitro. A glass suction microelectrode was used to record the electrical activity
      of single SLN units and a micropipette was used to pressure-eject small volumes
      of sodium cyanide (NaCN; 250-500 ng in 5 microl) near glomus tissue located at
      the main bifurcation of the SLN. The duration of the NaCN response and the number
      of spikes evoked after application of NaCN were compared in normoxia and
      hyperoxia (PO2 > 300 mmHg). Hyperoxia significantly reduced the duration and
      spike number of the NaCN response and a negative linear correlation existed
      between PO2 and response duration. In addition, hypoxia (PO2 < 60 mmHg) triggered
      SLN firing. Therefore, we can conclude that the paraganglia of the SLN are not
      only morphologically similar to the carotid body but are also excited by similar
      stimuli.

PMID- 15239963
TI  - Effects of gadolinium chloride on slowly adapting and rapidly adapting receptors
      of the rabbit lung.
AB  - Effects of gadolinium chloride, an inhibitor of stretch-activated channels, on
      the responses of slowly adapting receptors (SARs) and rapidly adapting receptors
      (RARs) to hyperinflation were investigated. The increase in activity of RARs
      resulting from sustained elevations of left atrial pressure (LAP) was also
      assessed with gadolinium chloride application. Action potentials (AP) of SARs and
      RARs during hyperinflation were recorded from the vagus nerve of anesthetized New
      Zealand White rabbits before and after application of gadolinium chloride (20mM)
      directly on the receptor area of the nerve endings. There was a significant
      reduction of activity in SARs (n = 9) and RARs (n = 7) after application of
      gadolinium chloride. Activity of RARs (n = 6) increased when the LAP was elevated
      by 5 and 10 mmHg. This effect was abolished after gadolinium chloride was applied
      to receptor endings and the activity was restored when gadolinium chloride was
      removed. This suggests that stretch-activated channels play a role in SARs and
      RARs activity.

PMID- 15239966
TI  - Acidosis abolishes the effect of repeated applications of ATP on pulmonary artery
      force and [Ca2+]i.
AB  - The purine nucleotide, ATP, can cause receptor-mediated desensitizing
      contractions of smooth muscle that may be modulated by pH. We investigated in the
      rat the effect of acidosis upon the contractile and Ca2+ responses induced by ATP
      upon intrapulmonary artery (PA) smooth muscle. Four successive applications of
      ATP (300 microM) at pH 7.4 induced desensitising contractile responses that
      showed progressively decreasing peak amplitudes that correlated with decreases of
      [Ca2+]i. Acidosis significantly reduced the peak contractile response to the
      first application of ATP without modifying the rate or degree of desensitisation
      in response to ATP and without decreasing the [Ca2+]i. Successive applications of
      ATP did not further reduce contractile force nor [Ca2+]i. These results
      demonstrated that acidosis abolishes the effect of repeat applications of ATP on
      pulmonary artery force and [Ca2+]i via alteration in the desensitization
      resensitisation characteristics of ATP receptor. This suggest a potentially
      important physiological role for changes in external pH in the regulation of ATP
      mediated control of the pulmonary circulation.

PMID- 15239965
TI  - Sustained muscle sympathetic activity after hypercapnic but not hypocapnic
      hypoxia in normal humans.
AB  - Exposure to hypercapnic hypoxia (asphyxia), but not hyperoxic hypercapnia,
      results in increased sympathetic activity that persists after exposure. To
      determine the contribution of CO2 to the post-hypoxia sympathoexcitation, we
      exposed 12 normal volunteers to hypocapnic and hypercapnic hypoxia (SaO2
      approximately 85%) for 20 min each on different days. We measured
      plethysmographic forearm blood flow, muscle sympathetic nerve activity (MSNA),
      mean arterial pressure (MAP), and heart rate. MSNA increased during both
      exposures but remained elevated for 15 min only after asphyxia. Following
      asphyxia, MAP returned to pre-exposure values, but after hypocapnic hypoxia MAP
      decreased below baseline for 15 min. There were sustained decreases in heart rate
      after hypocapnic, but not hypercapnic hypoxia. Forearm vascular resistance (FVR)
      decreased below baseline during both exposures, reached its highest value above
      baseline after asphyxia and then declined. After hypocapnic hypoxia FVR rose to
      baseline after exposure. Hemodynamics are differently altered by hypercapnic
      relative to hypocapnic 20 min hypoxia, while only hypercapnic hypoxia produces
      sustained elevation of MSNA during recovery.

PMID- 15239967
TI  - Prevention of bronchoconstriction in sensitized guinea pigs: efficacy of common
      prophylactic drugs.
AB  - Efficacy of beta2-agonists (B2), anticholinergics, corticosteroids, anti
      inflammatory drugs or antihistamines against methacholine, histamine, or allergen
      induced lung constriction was tested in ovalbumin sensitized guinea pigs. Airway
      resistance (Raw) and parenchymal damping (G) and elastance (H) were determined
      from low-frequency forced oscillatory input impedance (ZL). ZL was measured under
      control conditions, during iv infusions of methacholine, and following iv boluses
      of histamine or ovalbumin. In decreasing potency, ipratropium, salmeterol,
      fluticasone or cromoglycate reduced the methacholine-induced increases in Raw and
      G. Only antihistamines had any effects on the histamine-induced increased in Raw,
      G, and H. The ovalbumin-induced increases in Raw, G and H in the control animals
      (120 +/- 90%, 201 +/- 126%, 86 +/- 71%) were markedly reduced by pretreatments
      with antihistamines (18 +/- 11%, 13 +/- 9%, 3+/- 3%) and cromoglycate (29 +/-
      13%, 35 +/- 22%, 18 +/- 10%). Bronchoconstriction induced by muscarinic receptor
      stimulation is inhibited by anticholinergic, anti-inflammatory or beta2-agonist
      pretreatment; antihistaminic or anti-inflammatory premedication is beneficial if
      the release of histamine via an exposure to allergen is responsible for the fall
      in lung function.

PMID- 15239968
TI  - Depressed fatigue-induced oxidative stress in chronic hypoxemic humans and rats.
AB  - It was already documented that acute hypoxemia reduces the oxidative stress
      following static as well as dynamic handgrip bouts in humans. Then, we examined
      if chronic hypoxemia could produce the same effect in patients suffering from
      chronic respiratory insufficiency. In rats, we studied the respective consequence
      of a one-month exposure to normobaric hypoxia on two muscles (soleus, SOL, and
      extensor digitorum longus, EDL) which have high and low aerobic metabolism,
      respectively. Compared to healthy humans, the resting level of erythrocyte
      reduced glutathione (GSH) was significantly lower in chronic hypoxemic patients,
      and after a handgrip contraction sustained at 50% of maximal until exhaustion the
      GSH level and plasma thiobarbituric acid reactive substances (TBARS) did not
      vary. A 20-min period of oxygen supplementation partly restored the post-handgrip
      oxidative stress. Compared to control rats, SOL muscle of hypoxemic animals had
      lower intra-muscular resting level of GSH; after a 3-min muscle stimulation (MS)
      leading to fatigue, TBARS did not vary in SOL and EDL and the GSH decrease was
      absent in SOL whereas it persisted in EDL. We concluded that chronic hypoxemia
      depressed the fatigue-induced oxidative stress, the effects prevailing in muscles
      having a high oxygen demand.

PMID- 15239969
TI  - Protocol to measure acute cerebrovascular and ventilatory responses to isocapnic
      hypoxia in humans.
AB  - This study describes a protocol to determine acute cerebrovascular and
      ventilatory (AHVR) responses to hypoxia. Thirteen subjects undertook a protocol
      twice, 5 days apart. The protocol started with 8 min of eucapnic euoxia (end
      tidal P(CO2) (PET(CO2)= 1.5 Torr) above rest; end-tidal P(O2) (PET(O2)) = 88
      Torr) followed by six descending 90 s hypoxic steps (PET(O2) = 75.2, 64.0, 57.0,
      52.0, 48.2, 45.0 Torr). Then, PET(O2) was elevated to 300 Torr for 10 min while
      PET(O2) remained at eucapnia (5 min) then raised by 7.5 Torr (5 min). Peak blood
      flow velocity in the middle cerebral artery (MCA) and regional cerebral oxygen
      saturation (Sr(O2)) were measured with transcranial Doppler ultrasound and near
      infrared spectroscopy, respectively, and indices of acute hypoxic sensitivity
      were calculated (AHR(CBF) and AHRSr(O2)). Values for AHR(CBF), AHRSr(O2) and AHVR
      were 0.43 cm s(-1) % desaturation(-1), 0.80% % desaturation(-1) and 1.24l min(-1)
      % desaturation(-1), respectively. Coefficients of variation for AHR(CBF),
      AHRSr(O2) and AHVR were small (range = 8.0-15.2%). This protocol appears suitable
      to quantify cerebrovascular and ventilatory responses to acute isocapnic hypoxia.

PMID- 15239971
TI  - The story of gefitinib, an EGFR kinase that works in lung cancer.

PMID- 15239970
TI  - Adenosine A2A receptors interact with GABAergic pathways to modulate respiration
      in neonatal piglets.
AB  - GABA and adenosine contribute to respiratory inhibition in early postnatal life.
      In this study the adenosine A2A receptor agonist CGS21680 was used to evaluate
      adenosine receptor specificity and the interrelation of adenosine and GABA in the
      inhibition of inspiratory drive. In neonatal piglets (n = 10), CGS21680 was
      injected into the fourth ventricle resulting in apnea and/or decreased burst area
      and frequency of phrenic discharge. Phrenic burst area decreased to 58.9 +/- 8.6%
      (S.E.M.) after CGS21680 injection (control = 91.8 +/- 1.0%). Expiratory time
      increased 261.0 +/- 59.9% after CGS21680 from control (87.7 +/- 2.7%). When
      bicuculline was injected locally within the rostral ventrolateral medulla (n =
      5), or into the fourth ventricle (n = 5), the CGS21680 induced inhibition of
      phrenic was abolished. To define expression of A2A receptor at the message level
      (mRNA), we employed in situ hybridization with a digoxigenin-coupled
      oligonucleotide. Adenosine A2A receptor mRNA was expressed in regions of the
      medulla oblongata known to contain GABAergic neurons. We conclude that GABAergic
      inputs affecting respiratory timing and inspiratory drive are modulated by
      activation of A2A receptors. These findings offer new insight into the mechanism
      whereby xanthine therapy diminishes apnea of prematurity.

PMID- 15239972
TI  - Glia emerge as pain therapy targets.

PMID- 15239973
TI  - Up close and personal: anti-herpes drug development.

PMID- 15239974
TI  - Publish or perish.

PMID- 15239976
TI  - The new generation of patch-clamp equipment.

PMID- 15239975
TI  - Metabolic menages a trois: what does it mean for drug design?

PMID- 15239977
TI  - Imaging in oncology.

PMID- 15239978
TI  - Reliable high-throughput functional screening with 3-FABS.
AB  - An NMR method called 3-FABS has extended the capabilities of NMR, enabling rapid,
      efficient and reliable high-throughput functional screening for the
      identification of inhibitors and for measuring their 50% mean inhibition
      concentration (IC(50)) with accuracy. The substrate is tagged with a CF(3) moiety
      and (19)F NMR spectroscopy is used for the detection of the substrate and product
      components. We provide comprehensive insight into 3-FABS, a discussion of its
      strength and weakness when compared with other HTS techniques and a presentation
      of some of its applications to the screening of different enzymes and to multiple
      screening.

PMID- 15239979
TI  - Application of drug delivery technologies in lead candidate selection and
      optimization.
AB  - Formulation development during early drug discovery and lead optimization,
      involves several challenges including limited drug supply, the need for rapid
      turnaround, and limited development time. It is also desirable to develop initial
      formulations that will be representative of final commercial formulations.
      Nanoparticles offer a unique platform for the formulation of poorly soluble drugs
      - such formulations can be injected (intravenous, subcutaneous, intramuscular),
      as well as administered through other routes, such as oral, ocular and
      inhalation. Thus, a single formulation can be used to test and eventually develop
      multiple dosage forms. Furthermore, nanoparticles offer the opportunity for high
      drug loading, for low potency compounds, and thus support toxicological
      evaluation of such compounds.

PMID- 15239980
TI  - Using germ-line genetic variation to investigate and treat cancer.
AB  - For many years, there has been spirited debate as to the relative importance of
      environmental and genetic factors in the pathogenesis of cancer. Current efforts
      to annotate the human genome for germ-line genetic variants should establish the
      foundation for dissecting the contribution of genetics to the risk for cancer
      susceptibility. Population-based studies should be conducted to determine the
      influence of germline genetic variation on cancer outcomes, including the
      efficacy of anti-cancer drugs and the risk for life-threatening toxicities.
      Although we are early in the investigation of the influence of germline genetics
      on cancer outcomes, it is likely that, in the future, it will be possible to
      individualize therapeutic interventions. In turn, knowledge of genetic risk
      factors could afford opportunities for prevention, early intervention and
      minimization of deleterious toxicities associated with cancer therapy.

PMID- 15239985
TI  - Right hepatic artery injury associated with laparoscopic bile duct injury:
      incidence, mechanism, and consequences.
AB  - Because most bile duct injuries involve the common hepatic duct, the right
      hepatic artery, which is nearby, can also be injured. Reports on the frequency
      and significance of right hepatic artery injury (RHAI) associated with bile duct
      injury are sparse but suggest that RHAI increases mortality and decreases the
      success of the biliary repair. We studied the incidence, mechanism, and
      consequences of RHAI accompanying major bile duct injury. A total of 261
      laparoscopic bile duct injuries were analyzed. Distribution was as follows: class
      I, 6%; class II, 22%; class III, 61%; and class IV, 11%. RHAI was present in 84
      cases (32%): class I, 6%; class II, 17%; class III, 35% (P < 0.04 vs. class
      I/II); and class IV, 64% (P < 0.007 vs. class I/II/III). RHAI was more commonly
      associated with abscess, bleeding, hemobilia, right hepatic lobe ischemia, and
      subsequent hepatectomy (54% with RHAI vs. 11% without RHAI; P < 0.0001). RHAI had
      no influence on the success of the bile duct injury repair or on the mortality
      rate. Complications occurred more often with RHAI among cases repaired by the
      primary surgeon (41% RHAI vs. 2% no RHAI; P < 0.0001) but not among repairs by a
      biliary surgeon (3% RHAI vs. 2% no RHAI, P=NS; P < 0.0001 primary vs. biliary
      surgeon). RHAI increased morbidity, and occurred more often with class III and IV
      injuries reflecting the mechanisms of these injuries. RHAI did not increase the
      mortality rate or alter the success of biliary repair. Among biliary injuries
      repaired by the primary surgeon, RHAI was associated with a higher incidence of
      postoperative abscess, bleeding, hemobilia, hepatic ischemia, and the need for
      hepatic resection. A similar increase in the complication rate was not seen in
      patients treated by a biliary specialist.

PMID- 15239986
TI  - Central pancreatectomy with pancreaticogastrostomy for benign pancreatic
      pathology.
AB  - Benign lesions of the neck and proximal body of the pancreas pose an interesting
      surgical challenge. If the lesions are not amenable to simple enucleation,
      surgeons may be faced with the choice of performing a right-sided resection
      (pancreaticoduodenectomy) or a left-sided resection (distal pancreatectomy) to
      include the lesion, resulting in resection of a substantial amount of normal
      pancreatic parenchyma. Central pancreatic resection has been reported with Roux
      en-Y pancreaticojejunostomy reconstruction; however, this interrupts small bowel
      continuity and obligates an additional anastomosis. We have reviewed our
      experience with central pancreatectomy with pancreaticogastrostomy (PG) for
      benign central pancreatic pathology. Between January 1999 and December 2002, 14
      central pancreatectomies were performed with PG reconstruction. There were 7
      women and 7 men with a mean age of 60.9 years. Five resections were performed for
      islet cell tumors, three were performed for noninvasive intraductal papillary
      mucinous neoplasms, two were performed for serous cystadenoma, and one each was
      performed for a simple cyst, pseudocyst, mucinous metaplasia, and focal chronic
      pancreatitis. Seven out of 14 patients experienced a total of 10 complications.
      Pancreatic fistulae manifested by drainage of amylase-rich fluid from the
      operatively placed drains developed in 5 patients (36%). Reoperation or
      interventional radiologic procedures were not required in any patient with a
      fistula. Postoperative follow-up demonstrated 13 out of 14 patients to be alive
      and well without evidence of pancreatic insufficiency. One patient died at home
      on postoperative day 57 of cardiac pathology. Central pancreatectomy with PG is a
      safe and effective procedure that allows for preservation of pancreatic endocrine
      and exocrine function without disruption of enteric continuity. The complication
      of pancreatic fistula was managed conservatively via maintenance of operatively
      placed drains.

PMID- 15239987
TI  - Alimentary tract surgery in the nonagenarian: elective vs. emergent operations.
AB  - The objective of this study was to compare elective with emergent surgery in
      patients over the age of 90 years. We retrospectively reviewed the records of
      patients over 90 years of age who underwent alimentary tract surgery between 1994
      and 2002 at a community teaching hospital. Of 100 patients (mean age 92 years;
      range 90 to 98 years), 82 were women and 18 were men. Seventy-three percent were
      admitted from private homes or assisted-living facilities, and 27% came from a
      skilled-nursing facility (SNF). Major comorbid conditions existed in 93%.
      Procedures included right hemicolectomy (22%), adhesiolysis and/or small bowel
      resection (19%), cholecystectomy (14%), left-sided or sigmoid colectomy (11%),
      and perineal proctectomy (8%). Overall morbidity and mortality were 36% and 15%,
      respectively. Postoperative complications included respiratory failure and
      pneumonia (11%), arrhythmias (9%), delirium (7%), congestive heart failure and
      myocardial infarction (6%), and urinary complications (4%). Twenty-eight percent
      of the operations were elective, and 72% were emergent. Morbidity and mortality
      were higher in the emergent group (41% and 19%, respectively) than in the
      elective group (26% and 4%, respectively; P=0.04), especially for patients with
      an emergent surgical problem who came from a nursing home (22%). Average length
      of stay was 12 +/- 10 days (range 2 to 69 days) with little difference between
      elective and emergent cases. Sixty-four percent of patients were discharged to
      skilled-nursing facilities. Alimentary tract surgery can be performed safely in
      nonagenarians, and they should not be denied surgical care solely because of age.

PMID- 15239988
TI  - Safety and reliability of tattooing colorectal neoplasms prior to laparoscopic
      resection.
AB  - Accurate tumor localization is critical to performing minimally invasive
      colorectal resection. This study reviews the safety and reliability of tattooing
      colorectal neoplasms prior to laparoscopic resection. We retrospectively reviewed
      50 consecutive patients with colorectal neoplasms who underwent endoscopic
      tattooing prior to laparoscopic resection. Data were obtained from medical
      charts, endoscopy records, and pathology reports. No complications related to
      endoscopy or tattooing were incurred. Five neoplasms (10%) were in the ascending
      colon, five (10%) were in the transverse colon, eight (16%) were in the
      descending colon, 23 (46%) were in the sigmoid colon, and nine (18%) were in the
      rectum. Tattoos were visualized intraoperatively and accurately localized the
      neoplasm in 44 patients (88%). Six patients (12%) did not have tattoos visualized
      laparoscopically and required intraoperative localization. On average, the
      pathology specimens in this series had a 15 cm proximal margin, a 12 cm distal
      margin, and 15 lymph nodes. In the context of laparoscopic colorectal resection,
      preoperative endoscopic tattooing is a safe and reliable method of tumor
      localization in most cases. Localizing colon and proximal rectal lesions with
      tattoos may be preferable to other localization techniques including
      intraoperative endoscopy.

PMID- 15239989
TI  - Effect of high-dose steroids on anastomotic complications after proctocolectomy
      with ileal pouch-anal anastomosis.
AB  - This review was designed to determine whether "high-dose" steroid therapy (> or
      =20 mg prednisone/day) increases the likelihood of anastomotic complications
      after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The
      hospital records of 100 patients undergoing proctocolectomy with IPAA were
      reviewed. Patient characteristics were analyzed to determine what factors were
      associated with higher rates of anastomosis-related complications. Seventy-one of
      our patients were given diverting ileostomies, whereas the remaining 29 underwent
      a single-stage procedure. Fifty-four percent of the patients in our review were
      taking steroids preoperatively, 39 of whom were on high-dose therapy. The overall
      anastomosis-related complication rate was 14%. There was no significant
      difference in complication rates with respect to age, steroid use, steroid dose,
      use of a diverting ileostomy, type of anastomosis, duration of disease, or
      presence of backwash ileitis. A trend toward higher leakage rates was found in
      patients undergoing single-stage procedures (10.3% vs. 2.8%, P=0.14) as well as
      in patients undergoing single-stage procedures on high-dose steroids (22% vs.
      5.0, P=0.22). Nevertheless, neither of these trends was found to be statistically
      significant, which was likely influenced by the small sample size. Our data
      suggest that there may be an increase in anastomotic leakage rates in patients on
      high-dose steroids undergoing a single-stage proctocolectomy with IPAA.
      Nevertheless, our rate was not as high as the rates seen by other investigators
      and did not reach statistical significance. During preoperative counseling,
      patients on high-dose steroids should be informed of this uncertain but real risk
      of anastomotic leakage.

PMID- 15239990
TI  - Cost and effectiveness of follow-up examinations in patients with colorectal
      cancer resected for cure in a French population-based study.
AB  - The cost of follow-up examinations for patients having undergone potentially
      curative surgery for colorectal cancer is considerable. The aim of this study was
      to provide a thorough assessment of the cost and effectiveness of the follow-up
      tests used during the 5 years after surgical resection for colorectal cancer and
      its recurrences. We studied medical and economic data from the records of 256
      patients registered in the Herault Tumor Registry who underwent potentially
      curative surgical resection in 1992. Recurrence, curative recurrence, survival,
      and the cost of follow-up tests were assessed respectively for at least 5 years.
      We analyzed the cost and effectiveness of follow-up tests in patients who
      received either follow-up with carcinoembryonic antigen (CEA) monitoring as
      advocated by the 1998 French consensus conference recommendations (standard
      follow-up) or a more minimal follow-up schedule. Nine patients died in the
      postoperative period. The 5-year survival rates in the standard and minimal
      follow-up groups were 85% and 79%, respectively (p=0.25). Cost-effectiveness
      ratios were 2123 in Dukes' stage A patients, 4306 in Dukes' stage B patients, and
      9600 in Dukes' stage C patients. Cost-effectiveness ratios for CEA monitoring and
      abdominal ultrasonography per patient alive in the standard follow-up group were
      1238 and 2261.5, respectively. Cost-effectiveness ratios for CEA monitoring and
      abdominal ultrasonography per patient alive in the minimal follow-up group were
      1478 and 573, respectively. There were no survivors 5 years after a recurrence
      when the recurrence was detected by physical examination, chest X-ray, and
      colonoscopy in either follow-up group. Dukes' classification is a poor indicator
      of patient selection. The follow-up tests should only include CEA monitoring and
      abdominal ultrasonography for the diagnosis of recurrence.

PMID- 15239991
TI  - Clinical characteristics of familial adenomatous polyposis and management of
      duodenal adenomas.
AB  - The aim of this study was to evaluate the clinical characteristics of patients
      with familial adenomatous polyposis (FAP) undergoing surgical treatment over a 10
      year period and specifically to evaluate the incidence and clinical outcome of
      patients treated for duodenal adenomas. Patients with FAP who underwent surgical
      treatment for colonic polyposis at the University of Louisville from January 1992
      to July 2002 were investigated. Surgical treatment included colectomy and ileal J
      pouch-anal anastomosis (IPAA) or completion proctectomy with or without IPAA in
      those who had previously undergone subtotal colectomy elsewhere. All patients
      underwent screening gastroduodenoscopy at 3-year intervals beginning at the time
      of diagnosis or referral. Postoperative morbidity, mortality, and functional
      outcome were evaluated, as well as the occurrence of extracolonic manifestations
      and results of treatment for duodenal adenomas when required. Fifty-four patients
      were included in the study (mean age 28 +/- 2 years). Twenty-seven of them (50%)
      underwent colectomy and IPAA as the initial operation. Twenty-seven patients had
      previously undergone subtotal colectomy. Eight of these 27 patients had cancer in
      the rectum, of which three were T4 and one was T2N1 cancer. Twenty-two patients
      underwent a completion proctectomy and three required abdominoperineal resection.
      Twenty of the 54 patients developed duodenal adenomas. The mean age of diagnosis
      of duodenal disease was not significantly different from that of patients who
      were still free of duodenal polyps (40 +/- 11 vs. 34 +/- 12 years). Seven of
      these 20 patients underwent local excision of duodenal polyps (either
      endocopically or transduodenally); four of these patients developed recurrent
      disease. Six patients underwent pancreaticoduodenectomy for duodenal adenomas
      with severe dyplasia. These patients experienced an increased number of bowel
      movements, from five per day (range 4 to 8) to 10 per day (range 6 to 15). One
      patient required pouch excision and end ileostomy to control diarrhea. Our data
      demonstrate the following: (1) patients with FAP who have undergone prior
      subtotal colectomy and ileorectal anastomosis have a high risk of developing
      advanced cancer in the rectal stump; (2) duodenal adenomas are common in patients
      with FAP and may occur at an early age; (3) screening duodenoscopy should be
      initiated at the time of diagnosis of FAP; (4) local excision of duodenal
      adenomas is associated with a high risk of local recurrence; and (5) even though
      pancreaticoduodenectomy is the treatment of choice for advanced duodenal
      adenomas, this procedure may adversely affect pouch function in some patients.

PMID- 15239992
TI  - Diffuse pancreatic adenocarcinoma identified in an adult with annular pancreas.
AB  - Annular pancreas is a congenital anomaly resulting from malrotation of the
      pancreatic ventral bud. Although annular pancreas in the adult is rare, it may be
      recognized with increased frequency as a result of more liberal use of pancreatic
      imaging studies in patients with chronic abdominal pain and suspected chronic
      pancreatitis. Malignancy in the setting of annular pancreas is an uncommon event
      that has been reported previously but has almost always been related to the
      annular (ventral) segment. We report an interesting case in which pancreatic
      adenocarcinoma diffusely involving the dorsal (nonannular) segment presented in a
      middle-aged female patient. This unusual presentation points out the importance
      of considering neoplasia as part of the differential diagnosis and the
      possibility of pancreatic pathology in the dorsal, nonannular segment when there
      is no obvious duodenal or biliary obstruction involving the annular ventral
      segment.

PMID- 15239994
TI  - Effects of preceding gastrectomy on the outcome of pancreatoduodenectomy.
AB  - It is a complicated task to perform pancreatoduodenectomy for patients who
      previously had undergone gastrectomy. This paper reviewed our experience of eight
      pancreatoduodenectomies in gastrectomized patients. The indications for
      gastrectomy included gastric cancer in 3 patients, duodenal ulcer in 1 patient,
      and gastric ulcer in 4 patients. The interval between the two operations ranged
      from 15-254 months (average: 103 months). All patients underwent
      pancreatoduodenectomy, and the reconstruction after pancreatoduodenectomy was
      performed by the Whipple method, the Child method, or other complex Roux-en-Y
      type methods. All the patients recovered and were discharged without
      gastrointestinal disorder. The results suggest that the secondary
      pancreatoduodenectomy does not increase the mortality rate, although we should
      use the jejunal limb with less tissue damage at the anastomotic site of which
      circulation is well maintained for choledochojejunostomy and
      pancreaticojejunostomy. Furthermore, the jejunal limb should be lined carefully
      to avoid intestinal kinking and excess tension to the anastomosis.

PMID- 15239993
TI  - Cyst fluid tumor-associated trypsin inhibitor may be helpful in the
      differentiation of cystic pancreatic lesions.
AB  - In clinical practice it is important to differentiate pseudocysts from cystic
      pancreatic tumors, especially potentially malignant mucinous cystic tumors. We
      investigated three new markers-tumor-associated trypsin inhibitor (TATI) and the
      free alpha and beta subunits of human choriogonadotropin (hCGalpha and hCGbeta,
      respectively)-in the cyst fluid of patients with cystic pancreatic lesions and
      compared the concentrations of these markers to those of carcinoembryonic antigen
      (CEA), CA 19-9, CA 242, CA 125, CA 15-3, alpha-fetoprotein, and tissue
      polypeptide antigen in order to distinguish benign cysts from malignant cysts.
      Between 1995 and 2001, a total of 34 patients operated on for cystic pancreatic
      lesions at Tampere University Hospital were included. Cyst fluid was aspirated at
      operation and stored at -70 C. The histologic diagnosis was pseudocyst in 23
      patients, serous cystadenoma (SCA) in four patients, benign mucinous cystadenoma
      (MCA) in four patients, cystic papillary neoplasm (CPN) in one patient,
      glucagonoma in one patient, and malignant endocrine islet cell carcinoma (EC) in
      one patient. Significantly higher concentrations of TATI were found in patients
      with MCA and EC (2239 +/- 149 microg/L [mean +/- SEM]) than in patients with
      pseudocyst (55 +/- 29 microg/L; P=0.001) and in patients with SCA (36 +/- 23
      microg/L; P=0.01). The patient with CPN and the patient with glucagonoma had
      relatively low levels of TATI (30.7 and 46.5 microg/L). Mean CEA was higher in
      patients with MCA compared to those with pseudocysts (19,993 +/- 9418 vs. 53 +/-
      20 microg/L, P=0.002) and SCA (0.4 +/- 0.1 microg/L; P=0.02), but in the patient
      with malignant EC, the patient with CPN, and the patient with glucagonoma, CEA
      was normal. HCGalpha, hCGbeta, CA 19-9, CA 242, CA 125, CA 15-3, alpha
      fetoprotein, and tissue polypeptide antigen could not distinguish between MCA vs.
      pseudocyst or SCA, because both normal and elevated values were seen in all
      groups. To our knowledge, this is the first time that TATI has been quantitated
      in the cyst fluid of patients with cystic pancreatic lesions. It appears to be a
      potential marker in the differential diagnosis of benign from malignant cystic
      pancreatic lesions.

PMID- 15239995
TI  - Outcome of radical surgery for carcinoma of the gallbladder according to the
      tumor node metastasis and Japanese Society of Biliary Surgery stages.
AB  - Primary carcinoma of the gallbladder is a progressive, lethal disease. Survival
      of patients with this neoplasm depends strictly on lymph node involvement and
      depth of tumor invasion. The aim of the study was to evaluate the results of our
      surgical series according to the tumor node metastasis and Japanese Society of
      Biliary Surgery classification systems. A retrospective analysis of our 15-year
      experience was performed. Of the 79 patients with gallbladder carcinoma observed
      at our institution between 1984 and 2001, a radical resection was carried out in
      20 patients. Patients with stage I-II disease represent a minority of the cases
      of gallbladder carcinoma; the disease is localized in these patients, and
      surgical treatment provides the opportunity for good survival. Survival rates for
      patients with stage III-IV disease demonstrates that radical extended surgery
      offers the only chance for a relatively prolonged survival.

PMID- 15239996
TI  - Multiple focal nodular hyperplasia of the liver in a 21-year-old woman.
AB  - Focal nodular hyperplasia (FNH) is a relatively common condition, the diagnosis
      of which is now regularly made with diagnostic imaging. Cases of multiple FNH
      (more than four lesions) are rare, however, and the presence of numerous lesions
      may complicate the workup and diagnosis. We recently treated a young woman with
      multiple FNH. We report this case to highlight the clinical issues presented by
      this rare variant of a common benign hepatic disease.

PMID- 15239997
TI  - Hepatic resections using a water-cooled, high-density, monopolar device: a new
      technology for safer surgery.
AB  - Several techniques and devices have recently been developed in an effort to allow
      safer liver resections and avoid intraoperative blood loss. The aim of this study
      was to analyze our initial experience with hepatic resections using a new water
      cooled, high-density, monopolar device--the Tissuelink Monopolar Floating Ball
      (Tissuelink Medical, Inc., Dover, NH)--in order to avoid bleeding during hepatic
      surgery. We analyzed patients who underwent hepatic surgery between January and
      June 2003. Sex, age, type of disease, and type of surgical procedure, in
      association with the duration of the surgical procedure, blood loss, use of
      vascular clamping of the liver, length of hospital stay, morbidity, and mortality
      were analyzed. Seven minor liver resections, two major liver resections, and one
      total cystopericystectomy were performed with the use of this new device. Average
      blood loss was 150 ml (range 50 to 300 ml). No vascular clamping was used with
      the exception of one patient. No deaths were recorded. Morbidity included ascites
      in one case and pleural effusion in another. In conclusion, the Tissuelink
      Monopolar Floating Ball permitted excellent coagulation of the cut liver surface,
      thus avoiding bleeding and vascular clamping. As a result, postoperative
      morbidity and mortality were low.

PMID- 15239998
TI  - Ciliated hepatic foregut cyst of the left hepatic vein.
AB  - Ciliated hepatic foregut cyst is an extremely rare condition observed most
      frequently in the left hepatic lobe of young men. This report describes an
      unusual case of ciliated hepatic foregut cyst with involvement of the left
      hepatic vein in a 68-year-old woman. Preoperative imaging studies demonstrated
      characteristics of a solid tumor that were suggestive of a leiomyosarcoma of the
      inferior vena cava. Magnetic resonance venography confirmed a mass in the
      anterolateral wall of the inferior vena cava or in the left hepatic vein. This
      report confirms the unusual occurrence of this tumor and the confusing factors
      related to the diagnostic workup.

PMID- 15239999
TI  - A new free radical scavenger, edaravone, ameliorates oxidative liver damage due
      to ischemia-reperfusion in vitro and in vivo.
AB  - Ischemia-reperfusion injury causes oxidative stress producing reactive oxygen
      species, which is a serious problem linked to morbidity and mortality in liver
      surgery. We investigated the effects of edaravone, a new free radical scavenger,
      on liver oxidative stress in vitro and in vivo. We employed a hypoxia
      reoxygenation model of primary cultured hepatocytes using an AnaeroPack
      (Mitsubishi Gas Chemical Co., Tokyo, Japan). Hepatocytes were exposed to 3 or 4
      hours of hypoxia and then returned to oxygenation. We analyzed the time course
      changes of aspartate aminotransferase (AST), phosphatidylcholine hydroperoxide
      (PCOOH), and adenosine triphosphate (ATP) content in hepatocytes of edaravone
      treated groups or nontreated groups after reoxygenation. Edaravone significantly
      attenuated the elevation of the AST level of the medium and hepatocellular PCOOH
      and preserved the hepatocellular ATP level. In vivo, male Sprague-Dawley rats
      were subjected to 45 minutes of hepatic ischemia and 120 minutes of reperfusion.
      The rats were intravenously injected with vehicle or edaravone (3 mg/kg or 10
      mg/kg) before reperfusion and 1 hour after reperfusion. Serum AST levels and
      hepatic PCOOH and energy charge were significantly improved in both edaravone
      groups compared with control. In conclusion, edaravone has the ability to
      eliminate intra-hepatocellular superoxide species and attenuate oxidative liver
      damage in liver surgery.

PMID- 15240000
TI  - Surgery for ileal mesenteric lymphangioma during pregnancy: case report and
      review of the literature.
AB  - Mesenteric lymphangioma is one of the least frequently encountered types of
      benign tumor. This case report concerns a 31-year-old pregnant woman with a
      mesenteric cystic lymphangioma in the ileum. The multiloculated cystic mass was
      noted near the uterus by CT before the patient became pregnant. After becoming
      pregnant, she was followed without treatment for the asymptomatic mass. At 25
      weeks' gestation, however, she underwent emergency surgical treatment for small
      bowel obstruction. Concomitant small bowel resection was performed to remove the
      cyst. Herein we review seven reported cases of mesenteric benign tumor in
      pregnancy and explore the clinical features.

PMID- 15240001
TI  - A surgical rat model of human Roux-en-Y gastric bypass.
AB  - Obesity affects 30% of the United States population and its detrimental effects
      are obesity-related metabolic diseases. For patients refractory to conventional
      weight loss therapy, gastric bypass surgery is one of the proven methods for
      inducing a sustained weight loss and reversing the metabolic sequelae of obesity.
      To understand the mechanisms of weight loss and the amelioration of related
      metabolic comorbid conditions, a reproducible animal model is needed. We report
      our developmental experience with rat models of sequential Roux-en-Y gastric
      bypass after reproducing the diet-induced obesity that characterizes the
      hallmarks of human obesity. Four experiments were performed to induce weight
      reduction through successive modifications: In Experiment 1 a 20% stapled gastric
      pouch with a 16 cm biliary-pancreatic limb and a 10 cm alimentary limb
      accomplished sufficient weight loss within 10 days to ameliorate metabolic
      changes associated with obesity, but the occurrence of gastrogastric fistulas
      prevented sustained weight loss; in Experiment 2 the model was improved by
      dividing the stomach to avoid gastrogastric fistula, but again sustained weight
      loss was not achieved; in Experiment 3 the biliary-pancreatic limb was lengthened
      from 16 to 30 cm, reducing the common channel to approximately 18 cm. Sustained
      weight loss was achieved for 28 days. In Experiment 4 the model in Experiment 3
      was modified by dividing the stomach between two rows of staples. Sustained
      weight loss was observed for 67 days. We developed a reproducible rat model of
      Roux-en-Y gastric bypass. The existence of this model opens a new field of
      research in which to study the metabolic sequelae of obesity and the mechanisms
      of weight loss.

PMID- 15240002
TI  - Prognostic factors in patients with submucosal esophageal cancer.
AB  - The detection rate of early-stage esophageal cancer has increased recently.
      Various types of treatment including endoscopic mucosal resection, blunt
      dissection, and esophagectomy with extended lymphadenectomy are employed in
      patients with submucosal esophageal cancer. The purpose of the present study was
      to analyze prognostic factors in patients with submucosal esophageal cancer.
      Univariate analysis showed that lymph node metastasis, subdivision of tumor
      depth, and lymphatic invasion were correlated with prognosis, whereas sex, age,
      tumor location, surgical procedure, adjuvant therapy, histologic findings, and
      venous invasion did not affect prognosis. Multivariate analysis demonstrated
      lymph node metastasis to be the only significant prognostic factor in submucosal
      esophageal cancer. Although subdivisions of tumor depth did not reach
      significance as prognostic factors, lymph node metastasis was strongly related to
      tumor depth. To select the individualized treatment in patients with submucosal
      esophageal cancer, accurate diagnosis of lymph node metastasis necessitates a
      combination of imaging methods such as endoscopic ultrasound-guided fine-needle
      aspiration, computed tomography, and positron emission tomography.

PMID- 15240003
TI  - Laparoscopic colectomy for cancer.
AB  - Laparoscopic segmental colectomy has been widely accepted as a surgical procedure
      for benign colonic disease. With improving technology and surgeon experience,
      more complex procedures have been performed. However, a minimal invasive approach
      may not be justified for all colonic diseases. The use of laparoscopic surgery
      for colonic cancer, for example, has been controversial and the results of our
      national and international trials are yet unknown. We anticipate, given the
      positive findings of multiple small randomized and nonrandomized trials, that
      laparoscopic colectomy for cancer may soon prove to be appropriate in this
      setting. Our aim in this paper is to explore the indications, contraindications,
      and techniques regarding laparoscopic surgery that we have used in the treatment
      of colon cancer for patients enrolled in the national trial.

PMID- 15240004
TI  - Nuclear bodies and compartments: functional roles and cellular signalling in
      health and disease.
AB  - There is much interest in recent years in the possible role of different nuclear
      compartments and subnuclear domains in the regulation of gene expression,
      signalling, and cellular functions. The nucleus contains inositol phosphates,
      actin and actin-binding proteins and myosin isoforms, multiple protein kinases
      and phosphatases targeting Cdk-1 and Cdk-2, MAPK/SAPK, and Src-related kinases
      and their substrates, suggesting the implication of several signalling pathways
      in the intranuclear organization and function of nuclear bodies (NBs). NBs
      include the well-characterized Cajal bodies (CBs; or coiled bodies), the
      nucleolus, perinucleolar and perichromatin regions, additional NBs best
      illustrated by the promyelocytic leukemia nuclear bodies [PML-NBs, also named PML
      oncogenic dots (PODs), ND10, Kr-bodies] and similar intranuclear foci containing
      multi-molecular complexes with major role in DNA replication, surveillance, and
      repair, as well as messenger RNA and ribosomal RNA synthesis and assembly.
      Chromatin modifying proteins, such as the CBP acetyltransferase and type I
      histone deacetylase, accumulate at PML-NBs. PML-NBs and Cajal bodies are very
      dynamic and mobile within the nuclear space and are regulated by cellular stress
      (heat shock, apoptosis, senescence, heavy metal exposure, viral infection, and
      DNA damage responses). NBs strongly interact, using signalling mechanisms for the
      directional and ordered traffic of essential molecular components. NBs organize
      the delivery and storage of essential RNAs and proteins that play a role in
      transcription, pre-mRNA biosynthesis and splicing, and the sequestration and/or
      degradation of regulatory proteins, such as heterogenous nuclear ribonuclear
      proteins (hnRNPs), p53, Rb1, CBP, STAT3, and others. The objective of this review
      is to summarize some aspects of these nuclear structures/bodies/domains,
      including their proposed roles in cellular signalling and in human diseases,
      mainly neurodegenerative disorders and cancer.

PMID- 15240005
TI  - The Rheb family of GTP-binding proteins.
AB  - Rheb proteins represent a novel and unique family of the Ras superfamily GTP
      binding proteins that is conserved from yeast to human. Biochemical studies
      establish that they bind and hydrolyze GTP. Molecular modeling studies reveal a
      few structural differences between Rheb and Ras, which may suggest that residues
      involved in biochemical activities differ between the two G-proteins. The
      function of Rheb has been studied in a number of organisms that point to the
      involvement of Rheb in cell growth and cell cycle progression. In addition,
      studies in fungi suggest that Rheb is involved in arginine uptake. Further
      studies in Drosophila and mammalian cells have shown that the effects of Rheb on
      growth and cell cycle progression are mediated by the effect on the
      insulin/TOR/S6K signaling pathway. These studies have also shown that a complex
      consisting of the tuberous sclerosis gene products, Tsc1/Tsc2, serves as a GTPase
      activating protein (GAP) for Rheb, implying Rheb's role in this genetic disorder.
      Finally, Rheb proteins have been shown to be farnesylated and small molecule
      inhibitors of protein farnesyltransferase can block the ability of Rheb to
      activate the TOR/S6K signaling.

PMID- 15240006
TI  - The involvement of AU-rich element-binding proteins in p38 mitogen-activated
      protein kinase pathway-mediated mRNA stabilisation.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role
      in the post-transcriptional regulation of inflammatory genes. p38 has been found
      to regulate both the translation and the stability of inflammatory mRNAs. The
      mRNAs regulated by p38 share common AU-rich elements (ARE) present in their 3'
      untranslated regions. AREs act as mRNA instability determinants but also confer
      stabilisation of the mRNA by the p38 pathway. In recent years, AREs have shown to
      be binding sites for numerous proteins including HuR, TTP, AUF1, AUF2, FBP1, FBP2
      (KSRP), TIA-1, and TIAR. However, it is unclear which protein is responsible for
      mRNA stabilisation by p38. This review gives an overview of the major ARE-binding
      proteins and discusses reasons for and against their involvement in p38-mediated
      mRNA stabilisation.

PMID- 15240007
TI  - Mitogen-activated protein kinases Erk1/2 and p38 are required for maximal
      regulation of TIMP-1 by oncostatin M in murine fibroblasts.
AB  - Oncostatin M (OSM) regulates expression of various genes in connective tissue
      (CT) cells, including tissue inhibitor of metalloproteinases-1 (TIMP-1). In mouse
      fibroblast cell lines MLg, NIH 3T3 and primary mouse lung fibroblasts (MLF),
      murine OSM (muOSM) stimulated high TIMP-1 mRNA expression in comparison to
      leukemia inhibitory factor (LIF), epidermal growth factor (EGF), interleukin (IL)
      1beta and transforming growth factor (TGF)beta. In cell signaling, muOSM induced
      strong phosphorylation of extracellular-signal regulated protein kinase (Erk)
      1/2, p38 and Akt in addition to phosphorylation of signal transducer and
      activator of transcription (STAT) 1, STAT3 and STAT5 within 15 min. LIF and
      TGFbeta had no such effects. EGF stimulated comparable or lower Erk1/2, p38 and
      Akt phosphorylation while IL-1beta induced p38 phosphorylation in the fibroblast
      cell lines. The Erk1/2 inhibitor PD98059 and the p38 inhibitor SB203580 inhibited
      TIMP-1 mRNA response to muOSM, whereas the phosphoinositide 3-kinase (PI3K)
      inhibitor LY294002 enhanced the TIMP-1 mRNA response in NIH 3T3 and MLg cells.
      PD98059 and SB203580, but not LY294002, also inhibited fold induction of a
      chloramphenicol acetyltransferase (CAT) reporter gene driven by a minimal TIMP-1
      promoter that contained a proximal activator protein-1 (AP-1) site. Co
      transfection with JunB or c-Jun expression vector in NIH 3T3 cells caused marked
      transactivation of the TIMP-1 promoter/CAT reporter gene. muOSM caused a rapid
      increase of JunB and c-Jun protein in NIH 3T3 cells. PD98059 partially inhibited
      the increase of JunB, but not c-Jun, whereas SB203580 did not induce detectable
      changes in expression of either AP-1 factor in response to muOSM. These results
      demonstrate that Erk1/2 and p38 contribute to the elevation of muOSM induced TIMP
      1 expression, but PI3K does not, and suggest that Erk1/2 does so by enhancing
      JunB expression.

PMID- 15240008
TI  - Signaling "cross-talk" between TGF-beta1 and ECM signals in chondrocytic cells.
AB  - The objective of this investigation was to clarify how the integrin pathway
      modulates downstream effectors of the TGF-beta1 pathway in chondrocytic cell
      signaling. The levels of Smad2 and Smad3 phosphorylation upon TGF-beta1 or
      alpha2beta1 integrin (Type II collagen) stimulation were analyzed by Western
      blotting techniques. Cellular response was determined by quantitation of
      procollagen gene expression. Stimulation of cells with TGF-beta1 and Type II
      collagen led to rapid phosphorylation of Smad2 and 3 with phosphorylation peaking
      between 15 min and 1 h. Combined stimulation led to a synergistic increase in the
      phosphorylation of Smad2 and Smad3. Type II collagen gene expression paralleled
      Smad phosphorylation. Type II collagen modulates the TGF signaling cascade
      involving Smad2 and Smad3 leading to an increase in Type II collagen
      transcription. Therefore, we conclude that TGF-beta1 and integrin stimuli
      interact prior to Smad2 and 3 phosphorylation in the cytoplasm of chondrocytic
      cells and regulates the expression of ECM components in chondrocytes.

PMID- 15240009
TI  - Protein kinase A inhibits lysophosphatidic acid induction of serum response
      factor via alterations in the actin cytoskeleton.
AB  - Lysophosphatidic acid (LPA; 1-acyl-2-hydroxy-sn-glycero-3-phosphate) is a lipid
      growth factor that stimulates the proliferation of ovarian cancer cells. Recent
      studies indicate that elevation of cellular cAMP levels inhibits ovarian
      epithelial cancer cell growth. In this study, we investigated the effects of
      elevating cellular cAMP levels on LPA stimulation of OVCAR-3 ovarian cancer cell
      growth and on LPA stimulation of the serum response factor (SRF) transcription
      factor. Treatment of OVCAR-3 cells with forskolin and isobutylmethylxanthine
      (IBMX; 3-Isobutyl-1-methylxanthine) inhibited LPA stimulation of growth. LPA
      stimulation of SRF-mediated transcription was also inhibited in OVCAR-3 cells
      that were incubated with forskolin, dibutyryl cyclic AMP (db-cAMP), or paired
      cAMP analogues (N(6)-mono-tert-butylcarbamoyladenosine-3', 5'-cyclic
      monophosphate [6-MBC-cAMP] and Sp-5,6-DCl-BIMPS), which selectively activate type
      II protein kinase A. In contrast, incubation with a cAMP analogue (8-(4-chloro
      phenylthio)-2'-O-methyadenosine-3',5'-cyclic monophosphate [8CPT-2Me-cAMP]) that
      specifically activates the cAMP inducible Rap1 exchange factor, Epac, did not
      inhibit SRF. Similar results were obtained when HepG2 hepatoma cells, which do
      not express endogenous LPA receptors, were transfected with a single LPA receptor
      (LPA(1)). We observed that treatment of OVCAR-3 cells with forskolin greatly
      reduced both F-actin staining and focal adhesion labeling with anti-paxillin
      antibodies. Treatment of OVCAR-3 cells with the F-actin stabilizing compound,
      jasplakinolide, prevented the protein kinase A (PKA)-mediated inhibition of SRF.
      These results suggest that PKA inhibits LPA stimulation of SRF by promoting the
      dissolution of F-actin and that this is likely to contribute to the cAMP-mediated
      inhibition of ovarian cancer cell growth.

PMID- 15240010
TI  - Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein-Barr
      virus encoded latent membrane protein 1.
AB  - Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is essential
      for the immortalization of human B cells and is linked etiologically to several
      human tumors. LMP1 is an integral membrane protein which acts like a
      constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor
      associated factors (TRAFs), activates NFkappaB and triggers the transcription
      factor activating protein-1 (AP-1) via the c-Jun N-terminal kinase (JNK) cascade,
      but its specific contribution to AP-1 has not been elucidated fully. Members of
      AP-1 family, the Jun and fos related protein, have been shown to directly
      interact and form heterodimeric complexes. In this report, using a Tet-on LMP1
      HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma
      (NPC) cell line and the expression of LMP1 in which could be regulated by Tet-on
      system, we show that Jun B can efficiently form a new heterodimeric complex with
      the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser63,
      ser73) and Jun B involved in the process of the new heterodimeric form. We also
      find that this heterodimeric form can bind to the AP-1 consensus sequence.
      Transfection studies suggest that JNK interaction protein (JIP) could inhibit the
      heterodimer form of c-Jun and Jun B through blocking the AP-1 signaling pathway
      triggered by LMP1. The interaction and function between c-Jun protein and Jun B
      protein increase the repertoire of possible regulatory complexes by LMP1 that
      could play an important role in the regulation of transcription of specific
      cellular genes in the process of genesis of nasopharyngeal carcinoma.

PMID- 15240011
TI  - Intracellular signalings underlying bradykinin-induced matrix metalloproteinase-9
      expression in rat brain astrocyte-1.
AB  - Bradykinin (BK), an inflammatory mediator, has been shown to increase the
      expression of proteins such as matrix metalloproteinases (MMPs) on brain cells
      and contributes to the pathophysiology of inflammatory responses. However, the
      mechanisms regulating MMP-9 expression by BK in rat brain astrocytes-1 (RBA-1)
      remain unclear. Here we report that the mitogen-activated protein kinase (MAPK)
      and NF-kappaB pathways participate in the induction of MMP-9 expression induced
      by BK in RBA cells. Zymographic, Western blotting, and RT-PCR analyses showed
      that BK increased expression of MMP-9 mRNA and protein in a time- and
      concentration-dependent manner. BK-induced MMP-9 mRNA and protein expression was
      inhibited by MEK1/2 inhibitor PD98059, PI3-K inhibitor LY294002, and NF-kappaB
      inhibitor helenalin. In accordance with these findings, BK-induced
      phosphorylation of p42/p44 MAPK and Akt and activation of NF-kappaB was
      attenuated by prior treatment with PD98059, LY294002, and helenalin,
      respectively. The effects of BK on MMP-9 expression and p42/p44 MAPK and Akt
      phosphorylation were inhibited by B(2) receptor antagonist Hoe 140, indicating
      the involvement of B(2) receptors revealed by [(3)H]-BK binding assay.
      Furthermore, BK-stimulated translocation of NF-kappaB into the nucleus was
      revealed by Western blotting and immnofluorescence staining and blocked by
      Hoe140, PD98059, LY294002, and helenalin. Taken together, these results suggest
      that in RBA cells, activation of p42/p44 MAPK and Akt cascades mediated through
      NF-kappaB pathway are essential for BK-induced MMP-9 gene expression. This study
      may provide insights into the regulation of MMP-9 production in CNS, which may
      occur in vivo in pathological situations such as CNS inflammation and brain
      astrocytoma.

PMID- 15240012
TI  - Zinc inhibition of adenylyl cyclase correlates with conformational changes in the
      enzyme.
AB  - We have previously demonstrated that Zn(2+) inhibits hormone and forskolin
      stimulation of cAMP synthesis in intact N18TG2 cells, corresponding plasma
      membranes, and of recombinant adenylyl cyclase isoforms. If, however, the enzyme
      is pre-activated by hormone or forskolin, Zn(2+) inhibition is attenuated [J.
      Biol. Chem. 277 (2002) 11859]. We have extended our analyses of this inhibition
      to investigations of soluble adenylyl cyclase, composed of the CI and CII domains
      of the full-length protein. The properties of Zn(2+) inhibition of the soluble
      enzyme parallel that of the full-length protein, including the fact that
      inhibition is not competitive with Mg(2+). By monitoring intrinsic and extrinsic
      fluorescence, we demonstrate changes in enzyme conformers in response to the
      addition of varied effectors. The data suggest a possible mechanism by which
      Zn(2+) inhibits adenylyl cyclase activity.

PMID- 15240013
TI  - Synergistic activation of CREB-mediated transcription by forskolin and phorbol
      ester requires PKC and depends on the glutamine-rich Q2 transactivation domain.
AB  - Recruitment of a RNA polymerase II complex by the glutamine-rich Q2 domain of
      cAMP response element-binding protein (CREB) allows basal transcriptional
      activity, while recruitment of CBP/p300 through signal-induced phosphorylation of
      the kinase-inducible domain at serine-133 enhances CREB-dependent transcription.
      Here we demonstrate that co-administration of forskolin and phorbol ester TPA to
      NIH3T3 cells provoked a dose-dependent increase in phosphoserine-133. CREB- and
      Q2-dependent transcription, as well as transcription by other glutamine-rich
      transcription factors, but not by transcription factors lacking glutamine-rich
      regions, augmented synergistically in the presence of both stimuli. Synergistic
      activation was abograted by specific inhibition of protein kinase C (PKC), but
      not of PKA. Co-stimulation increased the basal activity of a minimal, CREB
      independent promoter. Therefore, Q2, which directly interacts with the RNA
      polymerase II initiation complex, may transmit the increased basal promoter
      activity provoked by these stimuli to CREB, thereby contributing to synergistic
      activation of CREB-mediated transcription. This synergism may have important
      implications on glutamine-rich transcription factor-target genes.

PMID- 15240014
TI  - Identification of human brain from a tissue fragment by detection of
      neurofilament proteins.
AB  - We developed a method for identifying human brain from a tissue-like fragment by
      detection of neurofilament protein (NF) using enzyme-linked immunosorbent assay
      (ELISA). NF was extracted from 0.1 g of organ/tissue homogenized with Tris-HCl
      buffer (pH 7.2) containing urea, phenylmethylsulfonyl fluoride (PMSF), EDTA and,
      EGTA. It was necessary to dilute the extract at more than 2(3)-fold to avoid
      immunosuppression by urea. Positive reaction was always obtained for NF-H in 2(3)
      fold diluted extract of brain tissue, however, NF-L and NF-M were not always
      detected when a brain fragment contained gray matter. Human cerebral white matter
      could be easily distinguished from other organs/tissues by detecting any of the
      NF-subunits. Brains of human and some animals could be discriminated by detecting
      NF-L or NF-M, although the species specificity of NF-H was not good. Our findings
      suggested that detection of NF-H was more useful than NF-L and NF-M for
      identifying a brain from a tissue-like fragment. The present ELISA method for NF
      H could identify human brain specimens under the following conditions: putrefied
      at 4 degrees C for up to 3 weeks, dried at 37 degrees C for at least 4 months,
      heated at 50 degrees C for at least 4 weeks. Our results showed that our method
      is useful for identification of brain tissue in forensic stain analysis. Two
      practical cases are described.

PMID- 15240015
TI  - Value of fetal autopsy after medical termination of pregnancy.
AB  - We carried out a retrospective study of 352 medical terminations of pregnancy
      (MTP) carried out in a large French administrative region over two consecutive
      years. We analysed the indications for MTP and then compared the prenatal
      ultrasound diagnosis with fetal autopsy findings in order to demonstrate the
      value of pathological examination of the fetus in prenatal diagnosis and genetic
      counselling as well as the need to check by autopsy the quality of ultrasound
      screening. Preliminary analysis of the indication for these MTP showed that in
      69.9% ultrasound screening had been carried out, revealing mainly brain
      abnormalities (22.2%) and heart defects generally associated with chromosomal
      abnormalities (32.1%). Prenatal findings were in agreement with autopsy results,
      showing no false-positive prenatal diagnoses. However, in 7.9% of cases in which
      brain abnormalities were detected, confirmation was not possible at autopsy
      because of tissue autolysis, showing the need for optimal conditions of
      expulsion. In 35.8% of cases, confirmation of the diagnosis by autopsy was not
      useful for management but still added to medical knowledge and demonstrated to
      the mother the reality of the defects. In 50.9%, the autopsy findings were
      decisive for genetic counselling.

PMID- 15240016
TI  - Indian homemade firearm--a technical review.
AB  - A wide variety of homemade (country made) firearms are involved in crime cases in
      India. These firearms are made up of very cheap material and are not safe for
      firing. Moreover, the country made firearms are different in their design,
      loading and locking mechanism, cocking and firing arrangements. In this paper we
      have studied the characteristic features of 300 country made firearms received
      for examination in the Central Forensic Science Laboratory (CFSL), Chandigarh
      during last two decades. The characteristic features of these firearms are so
      unique that the fired crime bullets or cartridges can easily be matched with the
      test. It is hoped that such information will be useful for firearm experts in
      case of interpretation.

PMID- 15240017
TI  - Particle size analysis of sediments, soils and related particulate materials for
      forensic purposes using laser granulometry.
AB  - Particle size is a fundamental property of any sediment, soil or dust deposit
      which can provide important clues to nature and provenance. For forensic work,
      the particle size distribution of sometimes very small samples requires precise
      determination using a rapid and reliable method with a high resolution. The
      Coulter trade mark LS230 laser granulometer offers rapid and accurate sizing of
      particles in the range 0.04-2000 microm for a variety of sample types, including
      soils, unconsolidated sediments, dusts, powders and other particulate materials.
      Reliable results are possible for sample weights of just 50 mg. Discrimination
      between samples is performed on the basis of the shape of the particle size
      curves and statistical measures of the size distributions. In routine forensic
      work laser granulometry data can rarely be used in isolation and should be
      considered in combination with results from other techniques to reach an overall
      conclusion.

PMID- 15240018
TI  - Impurity profiling of methamphetamine hydrochloride drugs seized in the
      Philippines.
AB  - Methamphetamine hydrochloride is one of the most widely used illicit drugs in the
      Philippines. In this study, we describe the application of cluster analysis of
      trace impurities in the profiling of the seized methamphetamine drug samples.
      Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5
      buffer solution and extracted with ethyl acetate containing three internal
      standards. The trace impurities were identified using gas chromatography-mass
      spectrometry (GC-MS) and quantified by gas chromatography with a flame ionization
      detector (GC-FID). Following previously reported methodologies, 30 impurity peaks
      were selected from the GC-FID chromatograms. The peak areas and retention times
      were referenced to the internal standards. The peak areas of the selected peaks
      were then grouped for cluster analysis. In order to check for consistency of
      clustering, two further cluster analyses were performed using 40 and 50 impurity
      peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks,
      while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the
      seized drug samples used in this study, cluster analysis using at least 40
      impurity peaks showed better consistency of clustering as compared to analysis
      using 30 peaks only. Ten of the impurity peaks were identified, of which four
      were identified for the first time in methamphetamine drug samples. These are p
      bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl
      methamphetamine. The presence of phenyl-2-propanone (P2P), N,N-dimethyl
      amphetamine, and N-formyl amphetamine is indicative that these casework samples
      were synthesized using the Leuckart method.

PMID- 15240019
TI  - Baboon taphonomy and its relevance to the investigation of large felid
      involvement in human forensic cases.
AB  - Eight complete baboon carcasses were fed individually to two captive leopards.
      These experimental feedings generated two separate bone assemblages, one composed
      of those bone specimens not ingested by the leopards (i.e., the refuse
      assemblage), and one composed of those bone specimens ingested and subsequently
      voided by the leopards (i.e., the scat assemblage). The two assemblages are
      separable using measurements of skeletal part representation. Distinguishing
      characteristics of the assemblages are summarized and explained in relation to
      observations of leopard feeding behavior and intrinsic qualities of baboon
      postcranial bones (i.e., bulk bone mineral density, maximum length, volume and
      cross-sectional area). Because baboons and humans share the fundamental primate
      body plan, these baboon carcasses approximate human cadavers ravaged by large
      felids. Thus, our results can inform death scene investigators about the expected
      human body part representation in large felid feeding residues versus those
      expected in regurgitations and feces. Since different body parts have different
      body-identification potentials, knowing these expected differences in body part
      representation is particularly valuable in forensic settings.

PMID- 15240020
TI  - A new 39-plex analysis method for SNPs including 15 blood group loci.
AB  - A novel 39-plex typing system for single nucleotide polymorphisms (SNPs) has been
      developed. This multiplex approach has the advantage of being able to type 38
      autosomal SNPs and one sex-discriminating base exchange site on the X and Y
      chromosomes rapidly and simultaneously. The SNP loci on the autosomes, which we
      examined, contain 15 loci distributed on blood type genes: three on RhCE, two
      each on Km and Gc, and one each on Duffy, AcP1, Tf, MN, GPT, EsD, PI, and Kidd
      genes. Thirty-seven genomic DNA fragments containing a total of 38 SNPs and one
      sex-discriminating site were amplified in one multiplex PCR reaction. Following
      the reaction, single nucleotide primer extension reaction was performed by
      dividing these SNP loci into five groups. The SNP type of each of the 39 loci was
      determined at one time by capillary electrophoresis using the newly designed
      multi-injection method. The combined PD (power of discrimination) of this typing
      system was (1-1.1) x 10(-14), and the MEC (mean exclusion chance) was 0.9990. We
      applied this system to forensic cases, including 16 paternity testing cases (13
      non-exclusion and three exclusion cases) and one personal identification case.
      For the paternity testing cases, the highest Essen-Moller's W-value was
      0.9999995. The pM (matching probability) of the personal identification case was
      2.22 x 10(-17). These data showed that this system was an excellent tool for use
      in forensic cases of paternity testing and personal identification.

PMID- 15240021
TI  - Y-STR haplotypes in Central Anatolia region of Turkey.
AB  - Allele frequencies and haplotypes of the 11 Y-chromosome STRs loci, namely DYS19,
      DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS438, and DYS439 were
      determined in a sample of 113 unrelated males from the Central Anatolia region of
      Turkey. In the 113 samples 106 different haplotypes were encountered, of which
      100 were observed only once. The overall haplotype diversity was 0.9987. In the
      study, a duplication at locus DYS19 and locus DYS393 was observed. The results
      demonstrate that these loci will be very useful for human identification in
      forensic cases and paternity tests in the Central Anatolia region.

PMID- 15240022
TI  - Allele distribution of 15 STR loci in a population sample of the Lithuanian
      minority residing in the Northeastern Poland.
AB  - Allele frequencies for the 15 STRs included in the AmpFlSTR Identifiler kit were
      determined in a population sample of 140 unrelated individuals of the Lithuanian
      minority residing in the Northeastern Poland. Departure from the Hardy-Weinberg
      equilibrium for loci VWA, TPOX and D7S820 did not sustain after applying
      Bonferroni correction for multiple testing. Exact tests disequilibrium analysis
      revealed five departures from independence out of 105 pair-wise comparisons. The
      combined MP and PE for all 15 loci are 5.00 x 10(-17) and 0.9999, respectively.

PMID- 15240023
TI  - Northern Polish population data and forensic usefulness of 15 autosomal STR loci.
AB  - Allele frequencies for the 15 STR loci in the AmpF/STR Identifiler kit (Applied
      Biosystems): D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S539, D2S1338,
      D19S433, VWA, TPOX, D18S51, D5S818, and FGA were determined in a sample of 145
      unrelated individuals living in the northern part of Poland. The values of
      heterozygosity, polymorphic information content (PIC), power of discrimination
      (PD), power of exclusion (PE), paternity index (PI) and matching probability
      (pM)were calculated.

PMID- 15240024
TI  - Nine-locus Y-chromosome STR profiling of Caucasian and Xhosa populations from
      Cape Town, South Africa.
AB  - Y-chromosome STR markers are not widely used in forensic case work in South
      Africa. To begin assessing the forensic value of these markers in South Africa,
      samples were collected from 100 English-speaking Caucasian males and 99 Xhosa
      males, living in the Cape Town metropolitan area. Allele and haplotype
      frequencies were determined for nine Y-chromosome STR loci (DYS19, DYS389-I,
      DYS389-II, DYS390, DYS391, DYS392, DYS393, and the duplicated locus DYS385).
      Unique haplotypes were obtained for 47 Xhosa males and 66 Caucasians.

PMID- 15240025
TI  - Population genetics of Y-chromosome STRs in a population of Podlasie,
      Northeastern Poland.
AB  - Haplotype and allele frequencies for the 12 Y-STRs were determined in a
      population sample of 186 Polish males. Five of the haplotypes were encountered in
      duplicate, while 176 haplotypes were unique. The overall gene diversity was
      0.9973. This database study provides an essential precondition for applying Y
      chromosomal STRs estimates in forensic identification of male DNA and tracing of
      paternal lineages.

PMID- 15240026
TI  - TIAFT2003. Proceedings of the 41st annual meeting of the International
      Association of Forensic Toxicologists. November 16-20, 2003. Melbourne,
      Australia.

PMID- 15240027
TI  - Wipe-test and patch-test for alcohol misuse based on the concentration ratio of
      fatty acid ethyl esters and squalene CFAEE/CSQ in skin surface lipids.
AB  - Fatty acid ethyl esters (FAEE) are known to be formed in blood and almost all
      human tissues after alcohol consumption and to be incorporated from sebum into
      hair where they can be used as long-term markers for excessive alcohol
      consumption. In order to examine whether skin surface lipids which consist mainly
      of sebum are an equally useful matrix for measurement of FAEE as alcohol abuse
      markers, samples were collected by a wipe-test from the forehead of 13
      teetotallers, 16 social drinkers, 10 death cases with known recent alcohol misuse
      and five death cases without indications of alcohol misuse. The samples were
      analysed by headspace solid-phase microextraction and gas chromatography-mass
      spectrometry for ethyl myristate, ethyl palmitate, ethyl oleate and ethyl
      stearate and by high performance liquid chromatography with photodiode array
      detector for squalene, (SQ), as a natural reference substance which the FAEE
      concentrations were related to. The ratio mFAEE/mSQ ranged between 0.16 and 1.12
      ng/microg (mean 0.34 ng/microg) for the teetotallers and between 0.08 and 0.94
      ng/microg (mean 0.37 ng/microg) for the social drinkers with no significant
      difference between both groups. For the alcoholics 2.4-24.2 ng/microg (mean 13.1
      ng/microg) were found. For two volunteers the course of mFAEE/mSQ 2 weeks before
      and 3 weeks after a single high alcohol dose was pursued by daily wipe tests. A
      strong increase of mFAEE/mSQ occurred between 7 and 12 days after the drinking
      event. This delay can be explained by the transition time of about 8 days between
      sebum production and its appearance on the skin surface known from literature.
      For seven social drinkers skin surface lipid samples were also collected using
      drug of abuse patches of the firm PharmCheck. The ratios mFAEE/mSQ in these
      samples were in the same range as from the wipe-test. The comparison with the
      self-reported ethanol amounts consumed the week before and during the test gave
      no good correlation (R2 = 0.42). It can be concluded from the results that FAEE
      in skin surface lipids can be used for medium-term retrospective detection of
      heavy drinking.

PMID- 15240028
TI  - Comprehensive two-dimensional gas chromatography with time-of-flight mass
      spectrometry (GC x GC-TOFMS) for drug screening and confirmation.
AB  - Comprehensive two-dimensional gas chromatography (GC x GC) is applied to analysis
      of drug standard mixtures containing 78 drugs of interest in forensic samples.
      For this study, underivatised drugs were employed. While several of the drugs
      were not detected at the low concentrations employed in the samples, most could
      be satisfactorily assigned their first and second dimension retentions in the GC
      x GC retention plane. For this study, time-of-flight mass spectrometry (TOFMS)
      detection was used. The enhanced separation possible in GC x GC is demonstrated,
      and typical linearity and apparatus precision are shown for tramadol, diazepam,
      olanzapine and desipramine using selected qualifier ions. Mass spectral library
      search quality for the detection of drugs in a selection of authentic forensic
      cases, along with retention position in the 2D retention plane, is used to
      support positive identification of the presence of the drugs. The analysis of
      'difficult' drugs paracetamol and phenytoin is shown to produce anomalous
      chromatographic peak shape in the 2D plane, whereas most drugs gave acceptable
      peak shapes. The GC x GC technique was applied to screening drugs in forensic
      samples, with either flame ionisation (FID) or TOFMS detection, and compared
      favourably with conventional single column GC-MS analysis when tested for
      diazepam in an authentic forensic study.

PMID- 15240029
TI  - Searching for new markers of endogenous steroid administration in athletes:
      "looking outside the metabolic box".
AB  - A simple means of detecting the abuse of steroids that also occur naturally is a
      problem facing doping control laboratories. Specific markers are required to
      allow the detection of the administration of these steroids. These markers are
      commonly measured using a set of data obtained from the screening of samples by
      gas chromatography-mass spectrometry (GC-MS). Doping control laboratories further
      need to confirm identified abuse using techniques such as gas chromatography
      combustion-isotope ratio mass spectrometry (GC-C-IRMS). An interesting urinary
      species was found while following the pharmacokinetics and changes to the steroid
      profile from single and multiple oral doses of the International Olympic
      Committee/World Anti Doping Agency (IOC/WADA) prohibited substance,
      dehydroepiandrosterone (DHEA). The urine samples collected from the
      administration studies were subject to GC-MS and GC-C-IRMS steroid analysis
      following cleanup by solid phase extraction techniques. A useful urinary product
      of DHEA administration was detected in the urine samples from each of the
      administration studies and was identified by GC-MS experiments to be 3alpha,5
      cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo). This compound occurs
      naturally but the concentrations of 3alpha,5-cyclo were elevated following both
      the single DHEA administration (up to 385 ng/mL) and multiple DHEA
      administrations (up to 1240 ng/mL), in relation to those observed prior to these
      administrations (70 and 80 ng/mL, respectively). A reference distribution of
      urine samples collected from elite athletes (n = 632) enabled the natural
      concentration range of 3alpha,5-cyclo to be established (0-280 ng/mL), with a
      mean concentration of 22 ng/mL. Based on this an upper 3alpha,5-cyclo
      concentration limit of 140 ng/mL is proposed as a GC-MS screening marker of DHEA
      abuse in athletes. GC-C-IRMS analysis revealed significant 13C depletion of
      3alpha,5-cyclo following DHEA administration. In the single administration study,
      the delta13C value of 3alpha,5-cyclo changed from -24.3 per thousand to a minimum
      value of -31.1 per thousand at 9 h post-administration, before returning to its
      original value after 48 h. The multiple administration study had a minimum
      delta13C 3alpha,5-cyclo of -33.9 per thousand during the administration phase in
      contrast to the initial value of -24.2 per thousand. Preliminary studies have
      shown 3alpha,5-cyclo to most likely be produced from DHEA sulfate found at high
      levels in urine. The complementary use of GC-MS and GC-C-IRMS to identify new
      markers of steroid abuse and the application of screening criteria incorporating
      such markers could also be adapted by doping control laboratories to detect
      metabolites of androstenedione, testosterone and dihydrotestosterone abuse.

PMID- 15240031
TI  - The development and application of a rapid gas chromatography-mass spectrometry
      method to monitor buprenorphine withdrawal protocols.
AB  - There are several drug therapies that can be used to treat opiate abuse. One such
      treatment that is currently gaining wide acceptance is the use of the combined
      agonist/antagonist drug buprenorphine. As with all long-term treatments, there is
      a potential for compliance issues to arise, which establishes the need for a
      technique to facilitate the monitoring of individuals prescribed buprenorphine.
      One such method has been developed and applied to the routine monitoring of
      buprenorphine and its primary metabolite in urine. The method was found to be
      sensitive (limits of detection of 1.0 ng/mL for both buprenorphine and
      norbuprenorphine), reproducible and linear up to 2000 ng/mL. This article
      describes the application of this method to the analysis of specimens collected
      from subjects prescribed a reducing low-dose buprenorphine regimen (10.0-0.4 mg
      per day) for acute opiate detoxification. A significant relationship between the
      daily dose and the mean creatinine-corrected concentration of buprenorphine in
      the urine was observed, together with a relatively stable relationship between
      the ratio of the urinary concentrations of norbuprenorphine to buprenorphine
      across the dose range studied.

PMID- 15240030
TI  - Comparative regression analysis of concurrent elimination-phase blood and breath
      alcohol concentration measurements to determine hourly degradation rates.
AB  - Following the introduction of limit values for blood alcohol and breath alcohol
      concentrations of 0.5 g/kg and 0.25 mg/L, respectively, as provided under s. 24 a
      of the German Road Traffic Act the question is whether also breath alcohol
      concentrations can be back calculated to the time of the traffic offence in cases
      where it is definite that the person to be examined is in the period of alcohol
      elimination. To this end, a study was performed in which 56 healthy volunteers
      consumed 0.5, 0.8 and 1.0 g of ethanol mixed with fruit juice per kilogram of
      body weight over a period of 10-20 min. Calculations included all 391 pairs of
      concurrent blood alcohol and breath alcohol concentration values obtained after 2
      h following the end of drinking. All volunteers exceeded the peak value of the
      alcohol curve. The measured values included were above 0.1 g/kg and 0.05 mg/L.
      For an average intake of alcohol of 0.88 g/kg the following regression lines were
      calculated for the period starting 2 h after the end of drinking: blood alcohol
      concentration [g/kg] = 1.318 - 0.172 h and breath alcohol concentration [mg/L] =
      0.589 - 0.079 h. Subtracting the simple standard deviation from the mean value
      yielded hourly degradation rates above 0.1 g/kg and above 0.05 mg/L,
      respectively. Subtracting two standard deviations, the values fell below this
      level in both cases. In fact, back calculation of breath alcohol concentrations
      based on 0.05 mg/h seems to be possible for traffic offences if certain
      conditions are complied with, such as the use of Evidential 7110, a calibrated
      breath alcohol analyser approved by the Federal Physical-Technical Laboratory for
      measuring the breath alcohol concentration.

PMID- 15240032
TI  - Headspace solid phase microextraction for the gas chromatographic analysis of
      methyl-parathion in post-mortem human samples. Application in a suicide case by
      intravenous injection.
AB  - A simple and rapid procedure for the determination of methyl-parathion (m-p) in
      post-mortem biological samples was developed using headspace solid phase
      microextraction (SPME) and gas chromatography (GC) with nitrogen-phosphorous
      detection (NPD). Methyl-parathion was extracted on 85 microm polyacrylate SPME
      fiber. Salt addition, extraction temperature, and extraction time were optimized
      to enhance the sensitivity of the method. The linearity (y = 0.0473x - 0.0113, R2
      = 0.9992) and the dynamic range (0.1-40 microg/ml) were found very satisfactory.
      The recoveries of methyl-parathion were found to be 46% in spiked human whole
      blood, 53% in spiked homogenized liver tissue, and 54% in spiked homogenized
      kidney tissue compared with samples prepared in water. The coefficients of
      variations for 2, 4, and 20 microg/ml of methyl-parathion in blood ranged from
      0.9 to 5.1%, whereas the detection limit of the method was satisfactory (1 ng/ml
      in aqueous samples, 50 ng/ml in whole blood). The developed procedure was applied
      to post-mortem biological samples from a 21-year-old woman fatally poisoned
      (suicide) by intravenous injection of methyl-parathion. The intact insecticide
      was found in the post-mortem blood at a concentration of 24 microg/ml. No methyl
      parathion was detected in the liver, kidneys, and gastric contents.

PMID- 15240033
TI  - A neolignan-type impurity arising from the peracid oxidation reaction of anethole
      in the surreptitious synthesis of 4-methoxyamphetamine (PMA).
AB  - The neolignan-type substance 2,4-dimethyl-3,5-bis(4'-methoxyphenyl)
      tetrahydrofuran is presented as a new forensic marker compound for the peracid
      oxidation of anethole. It is hypothesized that the formation of a stable
      intermediary carbocation in the hydrolysis reaction of anethole epoxide is not
      only responsible for the presence of 1,2-diols (and its esters) and 4
      methoxyphenyl-2-propanone (PMP2P) but can also be the cause for the creation of
      this neolignan impurity due to interaction with anethole itself. Moreover, the
      applicability of this new forensic marker is demonstrated by its retrieval in
      clandestinely manufactured 4-methoxyamphetamine (PMA) preparations.

PMID- 15240034
TI  - Determination of glyphosate in biological fluids by 1H and 31P NMR spectroscopy.
AB  - Identification of glyphosate in four cases of poisoning, using nuclear magnetic
      resonance spectroscopy of biological fluids is reported. It has been performed by
      using a combination of 1H and 31P NMR analyses. Characterization of the N
      (phosphonomethyl) glycine herbicide was achieved by chemical shift considerations
      and coupling constant patterns: CH2-(P) presents specific resonance at 3.12 ppm
      and appears as a doublet with a H-P characteristic coupling constant of 12.3 Hz.
      Moreover, resonances due to isopropylamine were present, confirming the ingestion
      of the considered trade formulation. After a calibration step, quantitation was
      performed by 1H and 31P NMR spectroscopy. The benefit and reliability of NMR
      investigations of biological fluids are discussed, particularly when the clinical
      picture is quite confusing.

PMID- 15240035
TI  - Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and 11
      hydroxy-delta9-THC: cannabinoid metabolites to creatinine ratio study IV.
AB  - The objective of this study was to compare urinary excretion patterns of two
      cannabinoid metabolites in subjects with a history of chronic marijuana use. The
      first metabolite analyzed was nor-9-carboxy-delta9-tetrahydrocannabinol (delta9
      THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically
      inactive. The second metabolite 11-OH-delta9-THC is an active cannabinoid
      metabolite and is not routinely measured. Urine specimens were collected from
      four subjects on 12-20 occasions > or = 96 h apart in an uncontrolled clinical
      setting. Creatinine was analyzed in each urine specimen by the colorimetric
      modified Jaffe reaction on a SYVA 30R biochemical analyzer. All urine specimens
      analyzed for 11-OH-delta9-THC had screened positive for cannabinoids with the
      EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and
      submitted for delta9-THC-COOH confirmation by GC-MS (cut-off concentration 15
      ng/mL). Eleven-OH-delta9-THC was measured by GC-MS with a cut-off concentration
      of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated
      internal standards for quantitative analysis. The mean (range) of urinary delta9
      THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The
      mean (range) of delta9-THC-COOH/creatinine ratios (ng/mL delta9-THC-COOH/mmol/L
      creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-delta9-THC
      concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean
      (range) of 11-OH-delta9-THC/creatinine ratio (ng/mL 11-OH-delta9-THC/mmol/L
      creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for delta9
      THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for
      delta9 -THC-COOH and 51/63 (81%) were positive for 11-OH-delta9-THC. Overall, the
      concentrations of 11-OH-delta9-THC in urine specimens collected > or = 96 h apart
      were lower than delta9-THC-COOH concentrations in 50/51 of the urine specimens in
      this population. Further urinary cannabinoid excretion studies are needed to
      assess whether 11-OH-delta9-THC analyses have a role when assessing previous
      marijuana or hashish use in chronic users whose urine specimens remain positive
      for delta9-THC-COOH for an extended period of time after last drug use.

PMID- 15240036
TI  - Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine,
      blood, and hair specimens.
AB  - A solid-phase enzyme immunoassay involving microtiter plates was recently
      proposed by International Diagnostic Systems corporation (IDS) to screen for
      buprenorphine in human serum. The performance of the kit led us to investigate
      its applicability in other biological matrices such as urine or blood, and also
      hair specimens. Low concentrations of buprenorphine were detected with the ELISA
      test and confirmed by HPLC/MS (buprenorphine concentrations measured by HPLC/MS:
      0.3 ng/mL in urine, 0.2 ng/mL in blood, and 40 pg/mg in hair). The intra-assay
      precision values were 8.7% at 1 ng/mL of urine (n = 8), 11.5% at 2 ng/mL in serum
      (n = 8), and 11.5% at 250 pg/mg of hair (n = 8), respectively. The immunoassay
      had no cross-reactivity with dihydrocodeine, ethylmorphine, 6-monoacetylmorphine,
      pholcodine, propoxyphene, dextromoramide, dextrometorphan at 1 and 10 mg/L, or
      codeine, morphine, methadone, and its metabolite EDDP. A 1% cross-reactivity was
      measured for a norbuprenorphine concentration of 50 ng/mL. Finally, the
      immunoassay was validated by comparing authentic specimens results with those of
      a validated HPLC/MS method. From the 136 urine samples tested, 93 were positive
      (68.4%) after the ELISA screening test (cutoff: 0.5 ng/mL) and confirmed by
      HPLC/MS (buprenorphine concentrations: 0.3-2036 ng/mL). From the 108 blood or
      serum samples screened, 27 were positive (25%) after the ELISA test with a cutoff
      value of 0.5 ng/mL (buprenorphine concentrations: 0.2-13.3 ng/mL). Eighteen hair
      specimens were positive (72%) after the screening (cutoff: 10 pg/mg) and
      confirmed by LC/MS (buprenorphine concentrations: 40-360 pg/mg). The ELISA method
      produced false positive results in less than 21% of the cases, but no false
      negative results were observed with the immunological test. Four potential
      adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L,
      and sodium chloride 50 g/L) that were added to 10 positive urine specimens
      (buprenorphine concentrations in the range 5.3-15.6 ng/mL), did not cause a false
      negative response by the immunoassay.

PMID- 15240037
TI  - Windows of detection of zolpidem in urine and hair: application to two drug
      facilitated sexual assaults.
AB  - A LC-MS/MS method for the detection of zolpidem in hair was developed to detect
      this drug after a single dose in possible drug facilitated sexual assaults. To
      determine the window of detection of zolpidem in both urine and hair, three
      volunteers received a 10 mg dose. Urine specimens were collected each 12 h for
      144 h. Hair was sampled 3-5 weeks after exposure. Hair and urine extracts were
      separated on a Xterra MS C18 column using a gradient of acetonitrile and formate
      buffer. For each compound, detection was related to two daughter ions. Zolpidem
      was detected for up to 60 h in urine with peak concentrations obtained at 12 h. A
      single exposure to zolpidem was detected in hair at concentrations ranging from
      1.8 to 9.8 pg/mg. Hair analysis was applied to two possible criminal cases. In
      the first case, zolpidem tested positive in the corresponding hair segment at 4.4
      pg/mg. In the other case, zolpidem was detected in all the segments analyzed,
      demonstrating likely previous drug use in addition to recent exposure associated
      with a positive blood result.

PMID- 15240038
TI  - Miniaturized sample preparation method for determination of amphetamines in
      urine.
AB  - A simple and miniaturized sample preparation method for determination of
      amphetamines in urine was developed using on-column derivatization and gas
      chromatography-mass spectrometry (GC-MS). Urine was directly applied to the
      extraction column that was pre-packed with Extrelut and sodium carbonate.
      Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface
      of Extrelut. AP and MA were then converted to a free base and derivatized to N
      propoxycarbonyl derivatives using propylchloroformate on the column.
      Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA
      from urine were 100 and 102%, respectively. The calibration curves showed
      linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine
      samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP
      and MA were determined, the intra-day and inter-day coefficients of variation
      were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA
      intoxication. The results were compared and a good agreement was obtained with a
      HPLC method.

PMID- 15240039
TI  - Analytical investigations in a death case by suffocation in an argon atmosphere.
AB  - A 31-year-old engineer was found dead in a reaction vessel (diameter 0.8 m,
      height 1.8 m) of a bulb factory some minutes after he had entered it for repair
      work. Resuscitation attempts with artificial respiration were unsuccessful.
      Despite autopsy and usual toxicological analyses, no cause of death could be
      found. Since in the normal production process, argon was used as a protecting
      gas, the possibility of suffocation in an argon atmosphere was investigated. This
      was rendered more difficult because of the natural content of 0.93 vol.% argon in
      air and since the excessive argon could have been removed by the resuscitation
      attempts. Gas samples from larynx, esophagus, bronchi, and stomach, separated
      blood samples from both ventricles of the heart and from the vena iliaca externa
      as well as tissue samples from lung and liver were collected during autopsy into
      headspace vials in such a way that the loss of gas and a dilution by surrounding
      air was avoided as far as possible. The samples were analyzed by headspace GC-MS.
      The abundance of Ar+ (m/z = 40) was used for quantification with N2(2+) (m/z =
      14) as internal standard. The following argon concentrations were measured (mean
      values, case under investigation/comparison cases): gas from larynx 1.79/0.96
      vol.%, stomach gas 1.58/0.89 vol.%, heart blood (left ventricle) 7.2/2.7
      microg/mL, heart blood (right ventricle) 5.8/2.7 microg/mL, blood from vena
      iliaca externa 3.6/2.7 microg/mL. A clearly increased concentration was also
      found in lung tissue, whereas in liver tissue no significant difference in
      comparison to other cases was measured. From the results, it follows that the
      deceased inhaled an increased amount of argon a short time before death. The
      concentrations are consistent with asphyxia and subsequent resuscitation
      attempts. They cannot be explained by a long-term inhalation of an atmosphere
      enriched with argon before the incident as it is likely to have occurred in this
      factory hall.

PMID- 15240040
TI  - GHB in postmortem toxicology. Discrimination between endogenous production from
      exposure using multiple specimens.
AB  - Since gamma-hydroxybutyrate (GHB) is present in both blood and urine of the
      general population as an endogenous compound, toxicologists must be able to
      discriminate between these endogenous levels and a concentration resulting from
      exogenous exposure. The implementation of a cut-off concentration must be done
      cautiously, due to the wide distribution of endogenous concentrations. To verify
      the accuracy of a proposed 50 mg/l postmortem blood cut-off, we tested 71 autopsy
      cases of subjects where the cause of death could exclude GHB exposure. The delay
      between death and autopsy ranged from 12 to 72 h. GHB was tested by gas
      chromatography-mass spectrometry (GC-MS) after precipitation. Briefly, 20 microl
      of blood, bile, or vitreous humor was pipetted in a glass tube, followed by 20
      microl of GHB-d6 and 45 microl of acetonitrile. After vortexing and
      centrifugation, the supernatant was collected and evaporated to dryness. The
      residue was derivatized with bis(trimethylsilyl)trifluoroacetamide (BSTFA) with
      1% trimethylchlorosilane (TMCS) for 20 min at 70 degrees C. After injection on a
      30 m HP5 MS capillary column, GHB (m/z 233, 204, and 147) and GHB-d6 (m/z 239)
      were identified by MS. GHB tested positive in all the 71 whole blood (cardiac)
      specimens, with concentrations in the range 0.4-409 mg/l, with a major
      distribution in the range 10-40 mg/l. A concentration >50 mg/l was observed in 14
      cases. As there was no data to support GHB exposure, this was considered as
      postmortem formation. In order to discriminate this contamination, when
      available, femoral blood, bile or/and, vitreous humor were tested. The following
      results were obtained: cardiac blood (55-409 mg/l) versus bile (6.1-238 mg/l) in
      seven cases; cardiac blood (51-409 mg/l) versus femoral blood (17-44 mg/l) in
      five cases, and cardiac blood (51-409 mg/l) versus vitreous humor (3.9-2 mg/l) in
      six cases. It is obvious that bile does not fit the requirements for
      discrimination and that femoral blood and mostly vitreous humor can be of
      particular interest. These results demonstrate that a positive (>50 mg/l)
      postmortem blood GHB concentration cannot support alone drug exposure and that it
      is essential to document the case with other specimens, including peripheral
      blood and vitreous humor.

PMID- 15240041
TI  - Poppy seed consumption and toxicological analysis of blood and urine samples.
AB  - Poppy seeds contain morphine in different amounts. Reported concentrations are up
      to 294 mg morphine/kg poppy seeds. Since penalties based on Street Traffic Law
      (parapgraph 24a StVG) in Germany (administrative offence) require definitive
      proof of morphine in blood samples, and the "Grenzwertkommission" in consultation
      with the Ministry of Transportation recommended a threshold of free morphine of
      10 ng/mL, the question arose whether the consumption of poppy seeds can lead to a
      blood concentrations equal or higher than 10 ng/mL of free morphine. Therefore,
      five volunteers ate poppy seed products (50 mg morphine/kg poppy seeds). In
      urine, all on-site tests were enzyme immunologically positive for opiates and
      were positive to morphine by GC/MS. All the blood samples were negative to
      morphine by EIA and to free morphine by GC/MS. However, after hydrolysis,
      morphine was detected by GC/MS in all cases. Accordingly, in Germany, penalties
      based on parapgraph 24a StVG are not likely to cause road users any concerns
      should they have consumed poppy seeds. Driver Licensing Authorities, however,
      should be advised of this problem to avoid unjustified legal measures.

PMID- 15240042
TI  - Has the cocaine epidemic arrived in the UK?
AB  - National surveys of the UK drug situation in 2000 found that cocaine was the most
      frequently seized Class A drug, with 25-40 tonnes of cocaine being smuggled into
      the UK each year. In the light of these findings, an audit of the analytical
      monitoring for cocaine abuse has been performed covering the period from 1996 to
      2002. It was found that there has been a consistent upward trend in the
      percentage of requests found to be positive for cocaine over this 7-year study
      period, rising from 9.7% in 1996 to 22% in 2002. This data would suggest that the
      use of cocaine has increased dramatically over the past few years, indicating
      that the arrival of the "cocaine epidemic" has now started to become a reality in
      the UK.

PMID- 15240043
TI  - Instability of pancuronium in postmortem blood and liver taken after a fatal
      intramuscular Pavulon injection.
AB  - The present study was designed to determine the stability of pancuronium in
      postmortem blood and liver during storage. Results were obtained using the method
      by Kerskes et al. [C.H.M. Kerskes, K.J. Lusthof, P.G.M. Zweipfenning, J.P.
      Franke, The detection and identification of quaternary nitrogen muscle relaxants
      in biological fluids and tissues by ion-trap LC-ESI-MS, J. Anal. Toxicol. 26
      (2002) 29-34.], modified and validated in our laboratory. Target analytes were
      isolated after enzymatic hydrolysis followed by solid phase extraction (BondElut
      C18 column). Internal standardisation was carried out using laudanosine and the
      target ions were monitored by LC-ESI-MS (monitoring ions m/z 358 for IS and 286
      for pancuronium). Materials were taken from a 46-year-old woman, who had been
      found dead. A syringe (2 ml) and an empty ampoule of Pavulon (4 mg/2 mL) were
      found in her hand. The residual volume of fluid in the syringe was 0.7 ml. An
      autopsy was performed six days after death. It revealed a needle mark on the left
      thigh. Postmortem materials (muscle from the injection site, blood and liver) and
      the syringe with fluid were stored for four months in a freezer at -20 degrees C.
      The initial pancuronium concentrations were 81 ng/mL in blood and 532 ng/g in
      liver. The analyte was stable when stored at -20 degrees C in blood even up to
      seven months. In liver samples its concentrations were variable. Pancuronium in
      blood stored at 20 degrees C underwent degradation very rapidly. After three
      months of storage these blood samples had concentrations not greater about 10% of
      the initial value. The degradation patterns of pancuronium depended on
      temperature and the biological matrix.

PMID- 15240044
TI  - Pesticide intoxications in the Centre of Portugal: three years analysis.
AB  - Pesticides are used in most countries around the world to protect agricultural
      and horticultural crops against damage. Poisoning by these toxicant agents occurs
      as a result of misuse or accidental exposure, and also by oral ingestion
      (voluntary or not). In Portugal, pesticide intoxications are still a cause of
      death, found in a considerable number of cases. The authors retrospectively
      examined the cases of pesticide poisoning in the Centre of Portugal, from
      autopsies performed in the Forensic Pathology Service of Coimbra's Delegation of
      the National Institute of Legal Medicine (NILM) and from other autopsies carried
      out in the Centre of Portugal, as well as some samples taken in hospitals in
      cases of suspected intoxication. In this study, the positive cases have been
      especially studied, in order to identify the pesticide used, as well as the
      etiology. The frequency of intoxications and its distribution by sex and age were
      also analyzed. Between January 2000 and December 2002, the Forensic Toxicology
      Laboratory received 639 pesticide analysis requests. In 2000, in a total of 149
      analysis requests, 30 cases were positive, 63.3% from male individuals and 36.7%
      from female. In 2001, the analysis requests increased to 240 as well as the
      positive cases (43), 74.4% from male individuals and 25.6% from female and in
      2002, the total cases analyzed also increased to 250, with 38 positive (73.6%
      from male individuals and 26.4% from female). Among the pesticides,
      organophosphorus insecticides still constitute the most important class detected
      in forensic intoxications, representing 63% of the total positive cases, followed
      by herbicides, with 33% of the positive results. Quinalphos is the most important
      organophosphorus insecticide, present in 32 of the 111 positive cases, followed
      by the herbicide paraquat, detected in 31 cases. The study emphasizes the
      increasing number of pesticide analyses, particularly relevant for the
      organophosphorus compounds and herbicides. Intoxication suspicion, accidental or
      voluntary, seems to be the most common cause of the incidents, for which analyses
      are requested, but it is also evident that the putative cause is unknown in a
      large number of cases. Therefore, more stringent legislation and enforcement
      regarding the sale and distribution of these toxic substances are needed.

PMID- 15240045
TI  - Forensic intoxication with clobazam: HPLC/DAD/MSD analysis.
AB  - Clobazam (Castillium, Urbanil), a benzodiazepine often used as an anxiolytic and
      in the treatment of epilepsy, is considered a relatively safe drug. The authors
      present a fatal case with a 49-year-old female, found dead at home. She had been
      undergoing psychiatric treatment and was a chronic alcoholic. The autopsy
      findings were unremarkable, except for multivisceral congestion, steatosis and a
      small piece of a plastic blister pack in the stomach. Bronchopneumonia,
      bronchitis and bronchiolitis were also diagnosed. Anhigh-performance liquid
      chromatography (HPLC)/diode array detector (DAD)/mass spectrometry detection
      (MSD) with electrospray method was developed in order to detect, confirm and
      quantify clobazam in the post-mortem samples. In the chromatographic separation,
      a reversed-phase column C18 (2.1 x 150 mm, 3.5 microm) was used with a mobile
      phase of methanol and water, at a 0.25 ml/min flow rate. Carbonate buffer (pH
      10.5) and 20 microl of prazepam (100 microg/ml) as internal standard were added
      to the samples. A simple and reliable liquid-liquid extraction method for the
      determination of clobazam in post-mortem samples was described. Calibration
      curves for clobazam were performed in blood, achieving linearity between 0.01 and
      10 microg/ml and a detection limit of 1.0 ng/ml. The clobazam concentration found
      in post-mortem blood was 3.9 microg/ml, higher than the reported therapeutic
      concentration (0.1-0.4 microg/ml). The simultaneous acquisition by photodiode
      array detection and mass spectrometry detection results allowed benzodiazepines
      to be identified with sufficient certainty. An examination of all the available
      information suggested that death resulted from respiratory depression due to
      clobazam toxicity.

PMID- 15240046
TI  - Three cases of sudden death due to butane or propane gas inhalation: analysis of
      tissues for gas components.
AB  - We report three cases of sudden death due to inhalation of portable cooking stove
      fuel (case 1), cigarette lighter fuel (case 2), and liquefied petroleum gas (LPG)
      (case 3). Specimens of blood, urine, stomach contents, brain, heart, lung, liver,
      kidney, and fat were collected and analyzed for propylene, propane, isobutane,
      and n-butane by headspace gas chromatography. n-Butane was the major substance
      among the volatiles found in the tissues of cases 1 and 2, and propane was the
      major substance in case 3. A combination of the autopsy findings and the gas
      analysis results revealed that the cause of death was ventricular fibrillation
      induced by hard muscle exercise after gas inhalation in cases 1 and 2, and that
      the cause of death in case 3 might be hypoxia. It is possible that the victim in
      case 3 was under anesthetic toxicity of accumulated isobutane which is a minor
      component of liquefied petroleum gas.

PMID- 15240047
TI  - A fatal case of mercuric cyanide poisoning.
AB  - A 57-year-old pharmacist was found dead 11 days after his disappearance. At the
      autopsy, samples of blood, urine, gastric content were obtained. Presence of
      ethanol, cyanide and mercury were detected in some samples. Cyanide and mercury
      were identified and quantified using high-performance liquid chromatography with
      diode array detector (HPLC) in fluorescence mode and ICP with mass selective
      detector (ICP-MS) respectively. Whole blood concentrations of ethanol was 1.72
      g/L. Cyanide and mercury concentrations in whole blood were respectively 0.16 and
      3.8 mg/L. Concentrations of cyanide (27 mg/L) and mercury (150 mg/L) in gastric
      contents prove a massive oral ingestion of mercuric cyanide or mercuric
      oxycyanide occurred. In this case report, the death was attributed to the
      combined toxicity of cyanide and mercury.

PMID- 15240048
TI  - Colchicine poisoning: case report of two suicides.
AB  - Colchicine overdose is uncommon but potentially life threatening because of the
      high toxicity of the drug. Poisoning by colchicine may occur following ingestion
      of medication used in acute attacks of gout and inflammatory diseases. We
      describe two cases involving suicide by the ingestion of medications marketed in
      France. In case 1, only heart blood was taken after body external examination. In
      case 2 an autopsy was performed and heart blood, urine, gastric contents and bile
      were taken for toxicological analysis. Colchicine was assayed in biological
      specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8,
      adding prazepam as internal standard (IS). Analyses were performed on a Symetry C
      8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer.
      Colchicine is eluted at 13.1 min and the method is linear for blood, urine and
      bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of
      colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66
      ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings
      are in the range of lethal concentrations previously described, but there is no
      correlation with the amount of ingested drug. Even after massive overdose, it
      could be impossible to detect colchicine in blood, and as there is a widespread
      enterohepatic recirculation before excretion in bile and feces, bile is the
      target sample to analyse. We conclude in both cases that the cause of death was
      suicide with colchicine. It appears very important to perform an autopsy in order
      to obtain bile, urine, heart blood and femoral blood.

PMID- 15240049
TI  - Segmentation and the pairing hypothesis.
AB  - The effect of stimulus contiguity and response contingency on responding in chain
      schedules was examined in two experiments. In Experiment 1, four pigeons were
      trained on two simple three-link chain schedules that alternated within sessions.
      Initial links were correlated with a variable-interval 30s schedule, and middle
      and terminal links were correlated with interdependent variable-interval 30s
      variable-interval 30s schedules. The combined duration of the interdependent
      schedules summed to 60s. The two chains differed with respect to signaling of the
      schedule components: a two-stimulus chain had one stimulus paired with the
      initial link and one stimulus paired with both the middle and the terminal link,
      while a three-stimulus chain had a different stimulus paired with the each of the
      three links. The results showed that the two-stimulus chain maintained lower
      initial-link responding than the three-stimulus chain. In Experiment 2, four
      pigeons were exposed to three separate conditions, the two- and three-stimulus
      chains of Experiment 1 and a three-stimulus chain that had a 3s delay to terminal
      link entry from the middle-link response that produced it. The two-stimulus chain
      maintained lower initial-link responding than the three-stimulus chain, as in
      Experiment 1, and a similar initial-link responding was maintained by the two
      stimulus chain and the three-stimulus chain with the delay contingency. The
      results demonstrate that a stimulus noncontiguous with food can maintain
      responding that is sometimes greater than a stimulus contiguous with food,
      depending on the response contingency for terminal-link entry. The results are
      contrary to the pairing hypothesis of conditioned reinforcement.

PMID- 15240050
TI  - Motivation and ability to walk for a food reward in fast- and slow-growing
      broilers to 12 weeks of age.
AB  - Poor physical abilities of broilers may prevent them from performing behaviours
      for which they are motivated. The aim of this study was to measure the influence
      of physical ability and motivation on the performance of broilers in short
      physical tasks. We tested birds from a fast- and a slow-growing broiler strain in
      a runway to 12 weeks of age. To manipulate motivation, half of the birds of each
      strain was feed deprived for 3h and the other half for 24h before testing. Each
      bird was tested in a control and a slalom runway test once a week. With a similar
      motivation, slow growers had a shorter latency to start walking and walked faster
      through the runway than fast growers in both tests. In fast growers walking speed
      decreased faster with age than in slow growers. Slow growers vocalised more in
      both tests. In the slalom test, 24h deprived birds vocalised more than 3h
      deprived birds. Although the fast and slow growers have a different genetic
      background, the results indicated that motivation is the dominant determinative
      factor for walking in birds with a low body weight, while physical ability is the
      dominant determinative factor for walking in birds with a high body weight.

PMID- 15240051
TI  - Locomotion induced by non-contingent intracranial electrical stimulation:
      Dopamine dependence and general characteristics.
AB  - Intracranial self-stimulation (ICSS) is induced by delivery of electrical
      stimulation contingent upon a response such as bar pressing. This procedure has
      been widely used to investigate the brain reward system. Recent investigations,
      however, have noted that non-contingent electrical stimulation, also called
      experimenter applied stimulation (EAS), produces a unique set of locomotion
      behaviors that appear to be related to ICSS, and that these behaviors resemble
      locomotion similar to those elicited by dopamine enhancing drugs. However, little
      is known about the general characteristics of EAS-induced locomotion. While ICSS
      appears to be robust, long lasting, and highly rewarding in that the rat will
      invest vast amounts of time or energy to obtain the electrical stimulation, these
      parameters have not been explored for EAS. Moreover, the dopamine dependence of
      EAS-evoked locomotion is also not firmly established. Thus, the present study
      investigated dopamine dependence and general characteristics of the EAS-induced
      locomotion to determine its similarity to ICSS. Results suggested that motor and
      limbic systems were strongly activated by non-contingent EAS, and that the
      resulting locomotion was dopamine dependent, robust, continued across long time
      horizons, and was greater than that evoked by contingent electrical stimulation.

PMID- 15240052
TI  - Energy budget versus temporal discounting as determinants of preference in risky
      choice.
AB  - Four pigeons and three ringneck doves responded on an operant simulation of
      natural foraging. After satisfying a schedule of reinforcement associated with
      search time, subjects could "accept" or "reject" another schedule of
      reinforcement associated with handling time. Two schedules of reinforcement were
      available, a variable interval, and a fixed interval with the same mean value.
      Food available in the session (a variable related to the energy budget) was
      manipulated in the different conditions either by increases of the value of the
      search state schedule of reinforcement, or by increases in the mean value of the
      handling state schedules. The results indicate that the amount of food available
      in the session did not affect the preference for variable schedules of
      reinforcement, as would be predicted by an influential theory of risk sensitive
      foraging. Instead, the preference for variability depended on the relationship
      between the time spent in the search and the handling states, as is predicted by
      a family of models of choice that are based on the temporal proximity to the
      reinforcer.

PMID- 15240053
TI  - Transitive inference and awareness in humans.
AB  - Thirty-nine participants performed a transitive inference task. During training,
      they were shown six pairs of imaginary sports teams and learnt which team was
      better in each pair. The pairs of teams were adjacent members of a seven-term
      series of team rankings (A-G). The participants were not explicitly informed of
      this underlying stimulus hierarchy. Once a participant reached the training
      criterion, they were tested on the six training pairs and three novel pairs (BD,
      CE, and DF) that required the participant to make a transitive inference. The
      participants completed a post-experimental questionnaire that measured their
      awareness of the stimulus hierarchy. A more-aware group and a less-aware group
      were created from answers to the questionnaire. The less-aware group were
      significantly less accurate than the more-aware group on some training pairs and
      all three novel pairs, and the less-aware group's pattern of performance bore
      similarities to non-human animal performance.

PMID- 15240055
TI  - Room novelty, sex, scopolamine and their interactions as determinants of general
      activity and rearing, and light-dark preferences in rats.
AB  - Male and female rats were assessed for effects of scopolamine on general
      activity, rearing and light-dark preferences when tested in either a familiar or
      a novel room. Males but not females reared more often when tested in the familiar
      rather than novel room, and the response was increased by scopolamine for all
      rats combined. Whereas scopolamine increased general activity for females (but
      not males) in the familiar room, it decreased the response for males (but not
      females) in the novel room. Females crossed more often between the dark and light
      sides of a light-dark box and, when treated with saline but not drug, spent more
      time in the light side than males. Scopolamine reduced the amount of time spent
      in the light side for females only. While the results were discussed mainly in
      terms of sex differences in fearfulness, their principal value was in
      demonstrating the effectiveness of room novelty and sex in determining levels of
      the behaviors recorded, and drug responsiveness.

PMID- 15240054
TI  - Influence of the estrous cycle on the behavior of rats in the elevated T-maze.
AB  - The elevated T-maze is an animal anxiety model which can discriminate between
      anxiety-like and fear-like behaviors. The estrous cycle is an important variable
      of the response in animal anxiety tests and is known to affect other models. The
      aim of the present study was to investigate the influence of the estrous cycle on
      behavior displayed in the elevated T-maze test. Seventeen male and 60 female rats
      were submitted to one session in this test, with the females being screened for
      the estrous cycle and divided into groups according to the various phases. The
      elevated T-maze had three arms of equal dimensions ( 50 cm x 10 cm), one enclosed
      by 40-cm high walls and perpendicular to the others, the apparatus being elevated
      50 cm above the floor. Each rat was placed in the end of the enclosed arm and the
      latency for it to leave this arm was recorded. These measurements were repeated
      three times separated by 30-s intervals (passive avoidance). After trial 3, each
      rat was placed at the distal end of the right open arm and the latency to exit
      this arm was recorded. Whenever latencies were greater than 300 s the trial was
      finished. The results demonstrated females in diestrus exhibited anxiety-like
      behaviors while females in metaestrus behaved in a similar way as the males.
      There were no differences between groups in fear-like behaviors. The results also
      indicate the elevated T-maze to be a sensitive test to measure anxiety.

PMID- 15240056
TI  - Evidence for time-place learning in the Morris water maze without food
      restriction but with increased response cost.
AB  - Time-place learning is the ability to distinguish between resources that vary in
      location at different times of day. Only one previous report has demonstrated
      successful time-place learning without using food as reward. In this experiment,
      satiated rats failed to form time-place discriminations in a Morris water maze
      while food deprived rats did, leading to the conclusion that food system
      activation is necessary for time-place learning. However, in addition to food
      system activation, response cost was also increased, which previously has been
      demonstrated to be effective in allowing the formation of time-place
      discriminations. The purpose of these two experiments is to test whether food
      system activation or heightened response cost allowed for time-place learning in
      the Morris water maze. In the first experiment, we replicate the failure to find
      time-place discriminations in the Morris water maze without food restriction and
      without increased response cost. In the second experiment, we found that
      increased response cost without food restriction was effective in allowing the
      formation of a time-place discrimination. The implications of this result are
      discussed in light of the timing mechanism used for time-place discriminations,
      the nature of the response cost, and the event-time-place tripartite association.

PMID- 15240057
TI  - Ethological validation and the assessment of anxiety-like behaviours:
      methodological comparison of classical analyses and structural approaches.
AB  - The research on emotional reactivity usually implies the use of standardised
      behavioural tests that provide a quick idea of the effect of a treatment on the
      reactivity of subjects to potentially dangerous situations. Many validity
      criteria have been considered to evaluate these tests. This validity concept
      supports the idea that animals' behaviour in these tests model human anxiety.
      Generally, those criteria repeatedly labelled as "ethological validation" refer
      to the analogy between animals and human in the meaning of the test situation.
      Although the content of the ethological validation concept is heterogeneous, it
      is steadily related to a fixed interpretation of the behavioural items produced
      in a given experimental setting. The basic assumption of such reasoning is that
      the behavioural items would always be expressed in the same behavioural context
      whatever the subject, its gender, strain or species, thoroughly asserting a
      predefined subjective state. Using multivariate and textual analysis, we found
      evidence that the "ethological validation" recourse to an a priori interpretation
      for a given behavioural variable may be deceptive. We defend the idea that the
      meaning of a behavioural variable should be restricted to the general context
      where it arose. Theoretical propositions and methodological options are
      discussed.

PMID- 15240058
TI  - A portrait of locomotor behaviour in Drosophila determined by a video-tracking
      paradigm.
AB  - This paper presents a detailed characterisation of locomotor behaviour of a
      single Drosophila fly freely walking in a small square arena. Locomotor activity
      is monitored by a video-tracking paradigm. Multiple parameters are extracted to
      construct the portrait of locomotor activity: the total distance moved, the
      number of episodes of activity and inactivity, the duration of activity, and the
      mean walking speed. To initiate a quantification of the fly's spatial walking
      movements, the number of passages in a virtual centre zone has also been
      determined. Moreover, to reveal the trajectory, as an index of fly's navigation
      ability, the turning angle, the angular velocity and the meander have been
      measured. Finally, we show that the number of episodes of inactivity as function
      of their duration follows a power law, while its counterpart, the episodes of
      activity does not, suggesting that the overall pattern of locomotor activity
      adheres to a fractal-like structure. Remarkably, the majority of these parameters
      are sexually dimorphic. This fine description of locomotor activity represents a
      new tool which will facilitate the study of the role of the different brain
      structures in the organisation of locomotor activity and the localisation of the
      fly's central pattern generator for locomotion and its motivational control.

PMID- 15240059
TI  - Serial order learning in associative formation.
AB  - Serial order learning was investigated in rats by delivering food to two
      spatially distinct feeders. All rats received three food pellets in feeder A
      delivered 10 min into the session. Three additional pellets were then delivered
      in feeder B after 20s, in Group Short (S), or 150 s, in Group Long (L). The rats
      in Group S learned the A-B association better than the rats in Group L. Of more
      interest, however, was that the rats in Group S showed more anticipatory
      responding to feeder A, suggesting subjects had better learned that feeder A
      delivered food "first". Implications for classical conditioning and serial order
      learning are considered.

PMID- 15240060
TI  - Corrosion resistance of iron-platinum magnets.
AB  - OBJECTIVES: The objective of this study was to investigate the corrosion
      resistance of the prototype iron-platinum (FePt) magnets and non-encapsulated
      neodymium-iron-boron (NdFeB) magnets in three different pH environments. METHODS:
      The corrosion resistance of the magnets was studied using a corrosion indicator,
      the breakaway force. The breakaway forces of the magnets after immersion in three
      media, namely 1% lactic acid solution (pH=2.7), 0.1% sodium sulphide solution
      (pH=12) and adjusted artificial saliva (pH=6.8) were compared after 28 and 60-day
      periods. RESULTS: By day 7, all NdFeB magnets dissolved completely in the acid
      medium, and they showed significantly lower breakaway forces at day 28 and day 60
      in artificial saliva (90%, 69%) and in alkaline medium (67%, 42%). In contrast,
      the FePt magnets did not show a drop in the breakaway forces after immersion in
      acid or artificial saliva, although approximately half of the original breakaway
      forces were recorded at day 28 and day 60 after immersion in strong alkali.
      CONCLUSIONS: The new iron-platinum magnets, which require no yoke assembly or
      protective casing, has good corrosion resistance for the oral environment. If its
      retentive force can be improved without increasing its thickness (0.3 mm), then
      it will have distinct advantages for clinical use.

PMID- 15240061
TI  - Importance of mini-dumbbell specimen to access tensile strength of restored
      dentine: historical background and the future perspective in dentistry.
AB  - OBJECTIVES: The development of adhesive resins to dentine enables resin
      restorations to be more durable. Several bond strength measurement techniques for
      measuring adhesion have been proposed. A standardised method is needed which
      produced higher and more consistent bond strength values which allow bond
      stability and the bonding mechanism to be studied. Our aim was to investigate
      mainly the adhesives and not the substrate. DATA SOURCES: This review is based on
      the literature on an adhesive, 4-META/MMA-TBB resin and conditioners to modify
      dentine substrates. The latter is a very important topic for developing our
      understanding of the bonding to dentine. The objective of the review is to
      explain the efficacy of the mini-dumbbell specimen in measuring the tensile
      strength of resin to dentine and to analyze the resin to dentine interface. Both
      the adhesive and the substrate control the quality of hybridized dentine.
      CONCLUSIONS: By creating an impermeable acid resistant barrier to both biological
      and chemical stimuli between the exposed dentine and the restored tooth surface
      we are able to protect exposed dentine from caries (infection) at the same time
      as protecting the pulp and preventing toothache. This barrier also helps maintain
      tooth vitality and for the purposes of this article is termed 'artificial
      enamel'. Microleakage free restorations are possible through the introduction of
      this 'impermeable artificial enamel' barrier.

PMID- 15240062
TI  - Microtensile bond strength of a dual-cure resin core material to glass and quartz
      fibre posts.
AB  - OBJECTIVES: To evaluate the microtensile bond strength (microTBS) of a dual-cure
      resin core material to different regions of fibre posts using different surface
      treatments. MATERIALS AND METHODS: Twenty-five silica zirconium glass fibre posts
      (Snowpost) and 25 quartz fibre posts (Aestheti-Plus) were used and randomly
      divided into five groups according to the surface treatments: (1) no surface
      treatment (Control) (2) dual-cure bonding agent, Clearfil Liner Bond 2V (LB) (3)
      LB followed by light curing for 20 s (LB and C) (4) silane coupling bonding agent
      agent, Clearfil Photobond with Porcelain Bond Activator (PB+PBA) (5) PB+PBA
      followed by light curing for 20 s (PB+PBA and LC). Treated posts were cemented
      into artificial post cavities using a dual-cure composite core material (Clearfil
      DC Core) and cured for 60 s from the top of the cavity. After 24 h storage in
      water, each specimen was serially sliced into 8, 0.6 x 0.6 mm2-thick beams for
      the microTBS test. The data were divided into three regions (upper/middle/bottom)
      and analyzed using three-way ANOVA and Dunnet's T3 multiple comparisons
      (alpha=0.05). RESULTS: There were no significant differences in bond strength
      between the three regions (p>0.05). The bond strengths were enhanced by the
      application of a silane coupling agent. For Snowpost, photoirradiation of the
      dual-cure bonding agent applied to the post surface significantly improved the
      bond strength (p<0.05) whereas it did not affect the bond strength of Aestheti
      Plus post (p>0.05). CONCLUSION: The bond strength between fibre post and dual
      cure resin core material depends upon the type of post and surface treatment.
      There were no regional differences in microTBS of the bonded post.

PMID- 15240063
TI  - Maximal bite forces in healthy young adults as predicted by surface
      electromyography.
AB  - OBJECTIVES: To assess the repeatability of maximal bite force estimates as
      obtained by submaximal electromyographic-force relationships performed
      simultaneously and symmetrically in both sides of the mouth. The protocol could
      be used in a clinical context to obtain indicative values for the occlusal loads
      to be resisted by the prosthetic reconstructions. METHODS: Ten young healthy
      subjects performed; (1) a maximum voluntary clench (MVC) directly on their
      occlusal surfaces; (2) four simultaneous recording of submaximal bite forces (98,
      196, 304 and 392 N on two transducers positioned on the left and right first
      mandibular molars) and surface EMG potentials of the masseter and temporalis
      anterior muscles. The actual force peak value was recorded. For each subject, a
      linear regression was run between the simultaneous bite force and EMG submaximal
      values recorded in the four tests. Using the EMG potentials obtained during the
      MVC tests, the best fitting line was used to estimate a maximum bite force. Two
      independent recordings were made by each subject (2 week interval) and analyzed
      by correlation analysis, paired Student's t-test, and Dahlberg statistic.
      RESULTS: Significant linear relationships were found between bite force and EMG
      potentials (p<0.01). The two series of indirect estimates of maximal bite force
      were correlated (r=0.626) without systematic differences (Student's t, p>0.01).
      Dahlberg statistic was 115.37 N (approximately 36% of the total variance of the
      group). CONCLUSIONS: Simultaneously recorded submaximal bite forces and surface
      EMG potentials of mandibular elevator muscles had a linear relationship. The
      estimates of maximum bite force were repeatable on a short-term basis (2 weeks).
      The method limited the disadvantages of bite force recordings, and it could be
      used to obtain indicative values for the occlusal loads to be resisted by the
      prosthetic reconstructions.

PMID- 15240064
TI  - Polymerization shrinkage: effects of boundary conditions and filling technique of
      resin composite restorations.
AB  - OBJECTIVE: To evaluate the linear polymerization shrinkage (LPS) and the effect
      of polymerization shrinkage of a resin composite and resin-dentin bond strength
      under different boundary conditions and filling techniques. METHODS: Two cavities
      (4 x 4 x 2 mm3) were prepared in bovine incisors (n=30). The teeth were divided
      into three groups, according to boundary conditions: In group TE, the total-etch
      technique was used. In group EE, only enamel was conditioned, and in group NE,
      none of the walls of the cavities were conditioned. A two-step adhesive system
      was applied to all cavities. The resin composite was inserted in one (B) or three
      increments (I) and light-cured with 600 mW/cm2 (80 s). The LPS (%) was measured
      in the top-bottom direction, by placing a probe in contact with resin composite
      during curing. Enamel and total mean gap widths were measured (400 x) in three
      slices obtained after sectioning the restorations. Then, the slices were
      sectioned again, either to obtain sticks from the adhesive interface from the
      bottom of the cavity or to obtain resin composite sticks (0.8 mm2) to be tested
      for tensile strength (Kratos machine, 0.5 mm/min). The data was subjected to a
      two-way repeated measures ANOVA and Tukey's test for comparison of the means
      (alpha=0.05). RESULTS: The highest percentage of LPS was found for the TE when
      bulk filled, and the lowest percentage of LPS was found in the EE and NE when
      incrementally filled. The resin-dentin bond strength was higher and the total
      mean gap width was lower for TE group; no significant effect was detected for the
      main factor filling techniques. No difference was detected for the tensile
      strength of resin composite among the experimental groups. CONCLUSIONS: The
      filling technique is not able to minimize effects of the polymerization
      shrinkage, and bonding to the cavity walls is necessary to assure reduced mean
      gap width and high bond strength values.

PMID- 15240065
TI  - The efficacy of a fluoride chewing gum on salivary fluoride concentration and
      plaque pH in children.
AB  - OBJECTIVES: The purpose of this study was therefore to study the influence of
      different chewing times on the salivary F concentration and on the recovery of
      plaque pH directly after a sucrose rinse on both the chewing and the non-chewing
      side. METHODS: For this purpose, one piece of sugar free chewing gum was chewed
      to 10 healthy subjects (aged 8-10 years, 5 male and 5 female children). Subjects
      refrained from toothbrushing for 3 days. On the fourth day, they rinsed for 1 min
      with 10 microl of a 10% sucrose solutions. After 8 min, chewing gum was given and
      started to chew for either 5, 10, 20, 30, 45 min or control (sucrose rinse).
      Thus, altogether six test sessions were repeated at one week intervals.
      Measurements of F concentration in saliva and pH of approximal plaque were
      carried out at two contralateral sites for up to 60 min. RESULTS: Higher salivary
      F concentrations were found on the chewing side than on the non-chewing side
      (expressed as) (p<0.05). But, the difference between the chewing and the non
      chewing side was not obvious for the plaque pH (expressed as AUC) (p>0.05).
      Therefore, this study showed that: (1) the F concentrations in saliva after
      chewing a F containing chewing gum had only small numerical differences among the
      various chewing times, with the exception for 5 min. All chewing time periods
      showed statistically significant differences between chewing and non-chewing
      side. (2) The prolonged chewing time increased the plaque pH recovery after a
      sucrose rinse (p<0.05) but there was no statistically significant difference on
      both of the chewing and non-chewing side (p>0.05). CONCLUSION: The results of
      this study indicated that a prolonged chewing time was favorable to the plaque pH
      recovery after a sucrose rinse and, to a certain extent, to the salivary fluoride
      concentration. Also it was shown that the F concentration in saliva was strongly
      dependent on which side the subject chewed on.

PMID- 15240067
TI  - Dental erosion, gastro-oesophageal reflux disease and saliva: how are they
      related?
AB  - AIMS: The purpose of this study was to assess the prevalence of tooth wear,
      symptoms of reflux and salivary parameters in a group of patients referred for
      investigation of gastro-oesophageal reflux disease (GORD) compared with a group
      of control subjects. MATERIALS AND METHODS: Tooth wear, stimulated salivary flow
      rate and buffering capacity and symptoms of GORD were assessed in patients
      attending an Oesophageal Laboratory. Patients had manometry and 24-h pH tests,
      which are the gold standard for the diagnosis of GORD. Tooth wear was assessed
      using a modification of the Smith and Knight tooth wear index. The results were
      compared to those obtained from a group of controls with no symptoms of GORD.
      RESULTS: Patients with symptoms of GORD and those subsequently diagnosed with
      GORD had higher total and palatal tooth wear (p<0.05). The buffering capacity of
      the stimulated saliva from the control subjects was greater than patients with
      symptoms of GORD (p<0.001). Patients with hoarseness had a lower salivary flow
      rate compared with those with no hoarseness. CONCLUSIONS: Tooth wear involving
      dentine was more prevalent in patients complaining of symptoms of GORD and those
      diagnosed as having GORD following 24-h pH monitoring than controls. Patients had
      poorer salivary buffering capacity than control subjects. Patients complaining of
      hoarseness had lower salivary flow rate than controls.

PMID- 15240066
TI  - Polymerisation characteristics of resin composites polymerised with different
      curing units.
AB  - OBJECTIVES: The aim of this study was to compare the plasma arc light source
      Apollo 95E and the conventional halogen lamp Elipar Visio regarding a number of
      polymerisation characteristics of different resin composites. METHODS: Four
      different resin composites (Arabesk Top, Herculite XRV, Pertac II, Tetric) were
      irradiated using the Apollo 95E unit for one, two or three cycles of 3 s and
      using the Elipar Visio unit for 40 s. The investigated polymerisation
      characteristics were: flexural strength and modulus of elasticity, bond strength
      to dentine, depth of polymerisation, and quantity of remaining double bonds. The
      data were treated statistically by analysis of variance and by Scheffe test.
      RESULTS: The modulus of elasticity and the flexural strength resulting from
      curing with Apollo 95E for 1 x 3 s were equal to or less than those resulting
      from curing with Elipar Visio. The bond strength to dentine and the depth of
      polymerisation with Apollo 95E used for 1 x 3 s were equal to or less than that
      obtained with the conventional lamp, depending on the resin composite.
      Irradiation of Herculite XRV resulted in a higher quantity of remaining double
      bonds than did Elipar Visio. In general, two or three curing cycles of 3 s with
      Apollo 95E were necessary to produce mechanical properties not significantly
      worse than with 40 s of conventional curing. CONCLUSIONS: The efficiency of
      plasma arc curing with Apollo 95E strongly depends on the resin composite. For
      most resin composites tested, plasma arc curing for 3 s resulted in inferior
      mechanical properties as compared to conventional curing.

PMID- 15240068
TI  - Effect of remaining demineralised dentine on dental microleakage accessed by a
      dye penetration: how to inhibit microleakage?
AB  - OBJECTIVES: To demonstrate that microleakage has taken place at the defect, which
      was analysed previously by a tensile test using dumbbell shaped specimens trimmed
      from bonded resin/dentine restorations, and to suggest how microleakage can be
      inhibited reliably in dental treatment. METHODS: A total of 60 Class V box
      cavities were prepared at the cemento-enamel junction on fresh bovine incisors
      and randomly divided into four groups of 15 specimens each. Exposure times of
      etching for 10:3 conditioner were set at 10, 30 or 60 s, and for 10% phosphoric
      acid (positive control) at 10 s. The cavity walls were rinsed with water for 10
      s, air-dried for 10 s and hybridised with 4-META/MMA-TBB resin. All the cavities
      were filled with a light cured resin composite and stored in 37 degrees C water
      for 24 h and then immersed in 15% methylene blue for 2 h. The length of dye
      penetration along the interface was graded by defined criteria and analysed using
      Kruskal-Wallis and Mann-Whitney tests. The dye penetration patterns were examined
      by light microscopy and the remaining demineralised dentine was analysed by
      Transmission Electron Microscopy (TEM). RESULTS: The least leakage score was
      obtained in 10s-10:3 etched group with 12 out of 15 specimens demonstrating no
      leakage. Leakage was significantly lower at the cementum margin than for the
      other three groups. No significant difference in the extent of greatest dye
      penetration was found between the 60s-10:3 and 10s-phosphoric etched groups. Dye
      penetration along the cementum margins was significantly higher than that of the
      enamel margins in all groups, except the 10s-10:3 etched group. TEM examination
      confirmed that there were exposed collagen fibrils in the remaining demineralised
      dentine, where microleakage had taken place. SIGNIFICANCE: It could be concluded
      from this study that microleakage has taken place at the defect in the bonded
      specimens which has correlations with zones of incompletely infiltrated
      demineralised dentine that was observed using TEM. A reliable method of
      inhibiting microleakage is the presence of well prepared hybridised dentine.

PMID- 15240069
TI  - New chromogenic plating media for detection and enumeration of pathogenic
      Listeria spp.--an overview.
AB  - In recent years a number of selective chromogenic plating media for pathogenic
      Listeria spp. have been developed and marketed. Their advantages are direct
      detection and enumeration of pathogenic Listeria spp. utilizing cleavage of
      substrates by the virulence factor phosphatidylinositol-phospholipase C (PI-PLC)
      and, to a lesser extent, by phosphatidylcholin-phospholipase C (PC-PLC). There
      are two groups of such media: the first utilizes cleavage by PI-PLC of L-alpha
      phosphatidyl-inositol, forming a white precipitation zone around the colony,
      combined with the chromogenic substrate 5-bromo-4-chloro-3-indoxyl-beta-D
      glucopyranoside for detection of beta-d-glucosidase, which occurs in all Listeria
      spp. All Listeria spp. produce turquoise colonies on these media which include
      ALOA , CHROMagar Listeria, BBL CHROMagar Listeria, and OCLA. The second group of
      media utilizes 5-bromo-4-chloro-3-indoxyl-myoinositol-1-phosphate, forming blue
      turquoise colonies of pathogenic Listeria spp. and white colonies of non
      pathogenic Listeria spp. BCM trade mark Listeria monocytogenes plating medium,
      Rapid'L.mono and LIMONO-Ident-Agar belong to this group. Selective chromogenic L.
      monocytogenes plating media offer the attraction of rapid economic detection and
      enumeration of pathogenic Listeria spp. within 24 or 48 h of incubation at 36+/-1
      degrees C. This overview summarises the characteristics of these chromogenic
      plating media, reviews important evaluations, and focuses on replacement of
      conventional by these chromogenic plating media, particularly for applications in
      the food industry.

PMID- 15240070
TI  - Spectrum of bacteriocin activity of Lactobacillus plantarum BS and fingerprinting
      by RAPD-PCR.
AB  - The spectrum of antimicrobial activity of Lactobacillus plantarum BS against
      representative bacterial species was established through deferred assay and 'spot
      on-lawn' assay using actively growing cells and partially purified bacteriocin
      extract, respectively. Only lactobacilli, pediococci, enterococci, bacilli and
      Listeria were inhibited from the test microorganisms. Slight bacteriocinogenic
      activity through 'spot-on-lawn' assay was detected against Staphylococcus aureus
      and Escherichia coli O157:H7. Random amplified polymorphic DNA-polymerase chain
      reaction (RAPD-PCR) analysis was used to compare the fingerprint of L. plantarum
      BS with other strains of L. plantarum. Using the 16S rRNA-based primer, P32, the
      bacteriocinogenic isolate exhibited identical RAPD-PCR fingerprints to L.
      plantarum ATCC 14917. Dendrograms derived from the Unweighted Pair Group Method
      with Arithmetic Mean (UPGMA) were constructed to show the similarity
      relationships among the investigated strains based on RAPD-PCR analysis. Bands
      differentiating L. plantarum BS from L. plantarum ATCC 14917 were also identified
      by varying the annealing temperature.

PMID- 15240071
TI  - Serotypes and virulence genes of ovine non-O157 Shiga toxin-producing Escherichia
      coli in Switzerland.
AB  - Sixty ovine STEC strains were examined with the aim (i) to serotype the strains,
      (ii) to characterize virulence factors, and (iii) to discuss possible
      associations between these factors and to assess the potential pathogenicity of
      these strains for humans. The 60 sorbitol-positive, non-O157 STEC strains
      belonged to 19 O:H serotypes, whereas 68% were of five serotypes (O87:H16, O91:H
      , O103:H2, O128:H2, O176:H4). 52% belonged to serotypes reported in association
      with HUS. Five serotypes were not previously reported in sheep strains. Of the 47
      strains encoding for stx1 variants, 57% were stx1c- and of the 45 encoding for
      stx2 variants, 80% were stx2d-positive. Eighty-two percent of the strains showed
      further putative virulence factors: 13% were eae-, 60% ehxA- and 67% saa
      positive. The associations between harboring (i) eae and stx1, stx2, ehxA or no
      saa and (ii) saa and stx1c or stx2d were significant (P<0.05). The strains
      belonged to 27 seropathotypes (association between serotypes and virulence
      factors), but 57% belonged to only six and O91:H-stx1 stx2d saa and O128:H2 stx1c
      stx2d ehxA saa were the most common. Seven of the eight intimin-positive strains
      harbored eae. Four strains of serotype O103:H2 and O121:H10 harboring stx2, eae
      and ehxA showed virulence factors typical for strains associated with severe
      human disease. However, according to the virulence factors, the majority of the
      ovine non-O157 STEC strains are assumed low-virulence variants. Nevertheless, as
      long as the contribution and interaction of these factors in milder disease
      remains unclear P, a certain risk for humans cannot be excluded.

PMID- 15240072
TI  - Prevalence of microbial biofilms on selected fresh produce and household
      surfaces.
AB  - Investigations of biofilms in domestic environments are sparsely represented in
      the literature. In this study, samples of various household surfaces, including
      food, laundry and kitchen items, were analyzed for evidence of biofilm presence.
      Visualization of the surfaces was carried out using cryostage scanning electron
      microscopy (CSEM) and light microscopy. Qualitative evidence of the presence of
      biofilm formation was obtained from all of the sample groups analyzed, suggesting
      the widespread existence of microorganisms in biofilms on domestic surfaces. This
      suggests that biofilms may be important in household hygiene, and highlights the
      need for standardized, approved biofilm methods suitable for consumer products
      testing.

PMID- 15240073
TI  - Prevalence and characteristics of Escherichia coli O157 from major food animals
      in Korea.
AB  - Escherichia coli O157:H7/NM (E. coli O157) is now recognized as an important
      cause of diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome worldwide.
      There have been several cases of human E. coli O157 infection in Korea since it
      was first isolated from a patient with hemolytic-uremic syndrome in 1998. Meat,
      other foods, and recreational and drinking water contaminated with animal feces
      are probably the major sources of the E. coli O157 infection. In this study, we
      investigated the prevalence of E. coli O157 in fecal and meat samples of cattle,
      pigs and chicken in Korea from April 2000 to July 2002. Eighty-six (3.03%) of
      2843 samples were positive for E. coli O157. Most of the E. coli O157 strains
      were isolated from fecal samples of beef and dairy cattle from May to October of
      each year. Of 86 E. coli O157 isolates, 73 were serotype O157:H7 and 13 were
      serotype O157:NM. Polymerase chain reaction (PCR) analysis of E. coli O157
      virulence markers revealed that all O157:H7/NM isolates were positive for EhlyA,
      eaeA and rfb(O157), and 77 isolates were positive for stx1 and/or stx2.
      Cytotoxicity analysis revealed that many of the E. coli O157 isolates showed high
      cytotoxicity on Vero cells. Our data suggest that the majority of Korean E. coli
      O157 isolates from food animals can cause serious diseases in humans.

PMID- 15240074
TI  - Occurrence and characterization of yeasts isolated from artisanal Fiore Sardo
      cheese.
AB  - The occurrence of yeast microflora in artisanal Fiore Sardo cheese during
      ripening was studied. Mean yeast counts ranged from 2.64+/-1 log(10) cfu ml(-1)
      in milk to 0.65+/-1 log(10) cfu g(-1) in 9 months cheese, with the higher counts
      observed in 48-h-old cheese. Strains belonging to the prevalent species
      Debaryomyces hansenii, Kluyveromyces lactis, Geotrichum candidum, Candida
      zeylanoides and Candida lambica were selected for technological and genotypic
      characterization. All D. hansenii strains fermented glucose and assimilated
      lactate, a high percentage assimilated citrate and only a few showed proteolytic
      and lipolytic activity. All K. lactis strains were able to both assimilate and
      ferment lactose, to assimilate lactate and to exhibit proteolytic activity on
      casein. G. candidum assimilated lactate and some strains showed proteolytic and
      lipolytic activity. C. zeylanoides showed lipolytic activity on tweens and the
      majority of strains assimilated citrate. C. lambica fermented glucose and
      assimilated lactate. Considering their diffusion and technological
      characteristics, an important role for K. lactis and G. candidum in the early
      stages of the ripening process and for D. hansenii after the first month of
      ripening can be suggested. RAPD-PCR analysis with M13 primer grouped the isolates
      in well-separated clusters with their type strains and confirmed the previous
      phenotypic identification. The high intraspecific homogeneity observed in tested
      strains could be explained by their isolation from a common substrate and from
      neighbouring geographical areas. This preliminary study allowed us to isolate
      autochthon yeast strains showing particular properties which can contribute to
      the production of typical cheese taste and flavour.

PMID- 15240075
TI  - Inactivation of Colletotrichum gloeosporioides spores by high hydrostatic
      pressure combined with citral or lemongrass essential oil.
AB  - Anthracnose, caused by the fungus Colletotrichum gloeosporioides, is the main
      post-harvest disease of the papaya. Inactivation of the spores of C.
      gloeosporioides in saline solution by the use of high hydrostatic pressure,
      citral oil and lemongrass oil, alone and in combination, was studied. C.
      gloeosporioides spores were efficiently inhibited after a pressure treatment of
      350 MPa for 30 min. When C. gloeosporioides was treated with 0.75 mg ml(-1) of
      citral or lemongrass oil, the pressure needed to achieve the same spore
      inhibition was 150 MPa. This work suggests the use of high hydrostatic pressure
      and plant essential oils as an alternative control for fruit diseases.

PMID- 15240076
TI  - Effect of weak acid preservatives on growth of bakery product spoilage fungi at
      different water activities and pH values.
AB  - Inhibition of spoilage organisms from bakery products by weak acid preservatives
      in concentrations of 0%, 0.003%, 0.03% and 0.3% (w/v) was investigated
      experimentally on a substrate media with water activity (a(w)) and pH ranging
      from sourdough-fermented acidic rye bread to alkaline intermediate moisture
      sponge cake types (a(w) 0.80-0.95, pH 4.7-7.4). Initially, rye bread conditions
      (a(w) 0.94-0.97 and pH 4.4-4.8) in combination with calcium propionate were
      investigated. Results showed that the highest concentration of propionate (0.3%)
      at all conditions apart from high a(w) (0.97) and high pH (4.8) totally inhibited
      fungal growth for a 2-week period, with the exception of Penicillium roqueforti,
      Penicillium commune and Eurotium rubrum. Characteristically for the major spoiler
      of rye bread, P. roqueforti, all three isolates tested were stimulated by
      propionate and the stimulation was significantly enhanced at high water activity
      levels. The effect of propionate on production of secondary metabolites
      (mycophenolic acid, rugulovasine, echinulin, flavoglaucin) was also studied, and
      variable or isolate dependent results were found. Subsequently, a screening
      experiment representing a wider range of bakery products was conducted using
      calcium propionate, potassium sorbate and sodium benzoate. The obtained data was
      modelled using survival analysis to determine 'spoilage-free time' for the fungi.
      At the low a(w) level (0.80) only Eurotium species grew within the test period of
      30 days. Higher water activity levels as well as higher pH values decreased
      spoilage-free times of the fungi. The preservative calcium propionate was less
      effective than potassium sorbate and sodium benzoate.

PMID- 15240077
TI  - Prediction of fungal growth and ochratoxin A production by Aspergillus ochraceus
      on irradiated barley grain as influenced by temperature and water activity.
AB  - Ochratoxin A (OTA) is a secondary metabolite of Aspergillus and Penicillium
      species, including Aspergillus ochraceus, a species that can be found in stored
      cereal grains such as barley. The objective of this study was to determine the
      effects of water activity (a(w), 0.80-0.99), temperature (10, 20, 30 degrees C),
      and A. ochraceus isolate differences on radial growth and OTA production in
      irradiated barley grains. The three isolates showed optimal conditions for growth
      and ochratoxin A production at 0.99 a(w) and 30 degrees C, with a marked decrease
      of growth rates and OTA production at the lowest levels of a(w) and temperature
      assayed. The minimum a(w) level for growth, observed in this study, was 0.85 and
      0.90 a(w) for OTA production. Significant differences among the isolates were
      found. Lag phases prior to fungal growth and OTA production values were modelled
      by multiple linear regression and response surface models. These models could
      provide an approximate prediction of growth and OTA production.

PMID- 15240078
TI  - Different genotypes of Yersinia enterocolitica 4/O:3 strains widely distributed
      in butcher shops in the Munich area.
AB  - The distribution of Yersinia spp. in butcher shops in the Munich area was
      studied. The isolates recovered were then characterised with pulsed-field gel
      electrophoresis (PFGE) to identify possible contamination routes. A total of 298
      samples were collected from eight small butcher shops between June and August in
      2001. Of these, 113 were surface samples from carcasses, offal and raw pork
      products, and 185 were environmental surface samples from tools, equipment and
      processing areas. The samples were studied with direct plating, overnight
      enrichment in nonselective broth and selective enrichment in two different
      enrichment broths. The Yersinia isolates recovered were characterised with PFGE
      using NotI, ApaI and XhoI DNA restriction enzymes. Yersinia was recovered from
      all eight butcher shops, and pathogenic Yersinia enterocolitica 4/O:3 was present
      in six shops. The occurrence of this pathogen on raw pork products varied from 8%
      to 25%. Pathogenic Y. enterocolitica 4/O:3 was isolated from two environmental
      samples: a worktable and a chain glove. Most (18/24) of the Yersinia-positive
      samples were found already after direct plating. Forty-nine Yersinia isolates
      from 24 samples were studied with PFGE. Twelve genotypes (I-XII) were obtained
      among Y. enterocolitica 4/O:3 when 33 isolates from 16 samples were characterised
      with NotI, ApaI and XhoI enzymes. The genotypes of Y. enterocolitica 4/O:3
      strains differed among butcher shops. In most (5/6) shops, more than one genotype
      was found, indicating different contamination sources. In conclusion, raw pork
      products from butcher shops are frequently contaminated with different genotypes
      of pathogenic Y. enterocolitica 4/O:3, thus serving as an important transmission
      vehicle from butcher shops to humans.

PMID- 15240079
TI  - Microbiological conditions of mechanically tenderized beef cuts prepared at four
      retail stores.
AB  - A group of 25 retail cuts of mechanically tenderized beef prepared during usual
      commercial operations at store facilities were obtained from each of four retail
      stores. Aerobes, coliforms, Escherichia coli and organisms that formed black or
      grey colonies on Harlequin agar (HA), a medium formulated for the recovery of
      Listeria, were enumerated in samples from the surfaces and the deep tissues of
      cuts. For the four groups of cuts, the mean numbers of aerobes on the surfaces of
      cuts differed by <1 log unit, but the numbers of aerobes recovered from the deep
      tissues differed by up to 2 log units. Few coliforms, E. coli or organisms that
      formed black or grey colonies on HA, which were mostly staphylococci, were
      recovered from surfaces and very few or none were recovered from deep tissues.
      Meat from the stores which provided product with the least or most bacteria in
      the deep tissues were cooked to maximum central temperatures that ranged from >63
      to <68 degrees C. Cooking reduced the numbers of aerobes in the deep tissues of
      most portions to <1 log cfu/10 g. Cooking to a medium rare condition may be
      adequate for assuring the microbiological safety of mechanically tenderized beef
      that is prepared without excessive contamination of deep tissues.

PMID- 15240080
TI  - Use of a probiotic Bifidobacterium in a dry food matrix, an in vivo study.
AB  - Probiotics are commonly included in dairy products. These products require cold
      storage and transportation, which limits their use. Here, we describe the
      inclusion of the probiotic strain Bifidobacterium lactis Bb-12 in a dry food
      matrix, an oat-based cereal bar, and its detection in faeces after consumption of
      this product. One week after cessation of B. lactis Bb-12 feeding, it could be
      identified in the faeces of five of the nine subjects.

PMID- 15240081
TI  - Korean women's attitudes toward breast cancer screening tests.
AB  - The purpose of the study was to explore Korean women's attitudes toward breast
      cancer screening tests from a feminist perspective. Twenty Korean women working
      in Dong-Dae-Moon Market in Seoul, South Korea were recruited using a convenience
      sampling method. Semi-structured in-depth interviews were conducted using an
      interview guideline that was developed for the study. The data were analyzed
      using a thematic analysis. The themes emerged from the analysis process included:
      "importance of breasts to women", "fearful, but not related to me", "bad previous
      experience", and "no need for a breast exam." Based on the findings, implications
      for nursing practice are proposed.

PMID- 15240082
TI  - The level of knowledge and views of the street children/youth about AIDS in
      Turkey.
AB  - The purpose of this study was to discover the level of knowledge and views of the
      street children and youth in Turkey about AIDS. Five focus group discussions were
      held with 44 children. On the data collection form there were questions about
      their age, status of working and living status on the streets, gender, source of
      information about AIDS, high-risk groups, and knowledge on the ways of
      transmission and getting protected from AIDS. According to the study results,
      more than half of the participants (56.8%) did not have any knowledge about AIDS.
      63.6% stated that they received their information about AIDS from public media.
      In addition, the participants of this study listed the main causes of
      transmission of AIDS as having sexual relationship with prostitutes (22.3%) and
      sharing razors, toothbrushes, footwear, food (27.6%). When asked the ways to
      protect oneself from AIDS, 28.9% stated that individual hygiene was very
      important while 21.0% stated not sleeping with prostitutes, single marriages, and
      condom use were very important ways to protect oneself from AIDS. 37 children of
      the total participants stated they were also at risk for AIDS. The main reasons
      of defining themselves at risk were being substance addicts (24.3%) and
      unhygienic practices (21.6%). The main conclusion of this study is that street
      children/youth have insufficient and incorrect knowledge about transmission and
      protection from AIDS and risk groups.

PMID- 15240083
TI  - Value congruence and job satisfaction among nurses: a human relations
      perspective.
AB  - The relationship between job satisfaction and value congruence within four
      organizational value areas was studied among nurses at surgery wards. Congruence
      between perceived and desired human relations values and social climate
      independently determined attitudes toward the nurse's ward. Social climate was
      operationalized as the habit of chatting with colleagues, and was inversely
      related to time pressure. Ward attitudes predicted job satisfaction, although
      structural equation modeling suggested that human relations value congruence also
      predicted job satisfaction directly, in addition to its effect through ward
      attitudes. Human relations value congruence thus appeared as an important
      ingredient of person-organization fit in nursing.

PMID- 15240084
TI  - A comparison of pressure ulcer prevalence: concerted data collection in the
      Netherlands and Germany.
AB  - OBJECTIVES: Because of a lack of epidemiological data of pressure ulcer (PU)
      among care dependent patients yearly prevalence measurements are held in the
      Netherlands and in Germany with identical methods. A comparison shows remarkable
      differences in the PU prevalence so that further analysis is needed to enlighten
      the reasons. DESIGN: With a standardized questionnaire all patients were examined
      by trained nurses of the participating facilities. SETTING: In-patients in 42
      Dutch and 10 German acute care Hospitals. PARTICIPANTS: All patients who handed
      in their informed consent were included. In the Netherlands n = 8734, and in
      Germany n = 2832. MAIN OUTCOME MEASURES: For calculating the PU prevalence the
      sample was divided inpatients at risk and not at risk for PU in accordance to the
      Bradenscale. Comparisons between the Netherlands and Germany refer to population
      details, quota of patients at risk for PU and PU prevalence. Finally the impact
      of eight controlled variables on the PU occurrence was calculated in a logistic
      regression. RESULTS: Both samples showed the same sex distribution, the same mean
      age and the same distribution among the medical specialties. The share of
      patients at risk for PU is higher in the Netherlands (55%) than in Germany (38%).
      The frequency of PU is higher in the Dutch population (22%) than in the German
      one (12%). Regarding only the risk-patients the differences reduce. The
      prevalence in the Netherlands was 33%, in Germany it was 28%. The highest impact
      on PU occurrence had the age and the length of stay in hospital. The Country
      ranges on third position. CONCLUSIONS: The Dutch sample had a higher share of
      risk-patients and a higher PU frequency. A standardization appropriate to a risk
      assessment reduce the differences. For enlightening the remaining differences
      further research is needed.

PMID- 15240085
TI  - Barriers to research utilisation among forensic mental health nurses.
AB  - This study used a cross-sectional, descriptive design to identify barriers to
      research utilisation among forensic mental health nurses. A postal questionnaire
      was sent to the total population of 88 registered nurses working in a forensic
      mental health hospital in the UK. Forty-seven responded representing a response
      rate of 53%. Results showed that the greatest barriers to research utilisation
      were those related to the characteristics of the setting in which nurses work or
      the personal characteristics of nurses themselves, which seems to be consistent
      with previous studies undertaken in the area. However, the nurses reported it
      especially difficult to trust what research shows because they feel that it is
      not always possible to apply those findings to their particular work environment.
      The main implications for policy are a need for an increase in support from
      management, programmes of advanced education to provide nurses with research
      skills, an improvement in accessibility and availability of research reports and
      an increase in time available to read and implement research. The main
      suggestions for future research are that qualitative studies should be carried
      out to attain a better understanding of mental health nurses' attitudes towards
      research utilisation.

PMID- 15240086
TI  - Being in the light or in the shade: persons with Parkinson's disease and their
      partners' experience of support.
AB  - Interviews with six couples, persons with Parkinson's disease and their partners,
      were tape-recorded, transcribed and analysed using manifest and latent content
      analysis. The couples' experiences could be interpreted as Being in the light and
      Being in the shade of support, with internal variations for the patients and
      their partners. The narratives also revealed that the disease meant a transition
      of roles in their relation seen in different patterns: From unity towards unity,
      From unity towards distance and From distance towards unity. The results indicate
      that there is a need for more specialised and individually adjusted support.

PMID- 15240087
TI  - Nurses' clinical decision-making regarding the management of pain.
AB  - Effective pain management remains an elusive goal within the profession of
      nursing. While considerable improvement has occurred, patients continue to
      experience inappropriate levels of pain. To date, research has focused on
      objective factors that influence pain management. Few studies have examined
      attitudinal factors that may influence nurses' decision-making. This quasi
      experiment was based on preliminary data showing that nurses' preconceived
      notions regarding certain patient groups influenced their management of pain. An
      intervention was tested for its' effect on nurses' preconceived notions regarding
      specific patient groups. A significant difference in a positive direction was
      found. Nurses were more willing to spend time and energy managing pain across all
      patient groups following the intervention.

PMID- 15240088
TI  - A randomized controlled trial of a mutual support group for family caregivers of
      patients with schizophrenia.
AB  - This randomized controlled trial examined the effectiveness of a 12-session
      mutual support group conducted over 3-months for Chinese family caregivers of a
      relative with schizophrenia compared with routine family support services in Hong
      Kong. Forty-eight family caregivers from two psychiatric outpatient clinics were
      allocated randomly to an experimental (mutual support and usual outpatient care)
      group (n = 24) or a control (usual outpatient care only) group (n = 24). Data
      were collected prior to, 1 week and 3 months after the intervention. Families
      allocated to the mutual support group experienced decreased levels of family
      burden and increased family functioning and these changes were significantly
      greater than those of the controls at both post-intervention time points. The
      experimental group also showed a significant decrease in the duration of patient
      re-hospitalization (the total number of days of psychiatric hospitalization) at 3
      months compared with the control group. This suggests that the mutual support
      group provided a more responsive service for patients than standard care.
      However, there was no significant difference in family service utilization
      between the two groups. The findings indicate that a mutual support group can
      provide benefits for family caregivers of people with schizophrenia that go
      beyond those provided by routine family support.

PMID- 15240089
TI  - Living in a group dwelling: how do residents spend their time in a psychiatric
      group dwelling?
AB  - The aim of the study was to investigate how residents at psychiatric group
      dwellings spend their time. The study consisted of two parts: questionnaires and
      an observation survey. It included all the staff at two municipal psychiatric
      group dwellings where the residents were primarily diagnosed as having long-term
      schizophrenia. This study indicated that, even if the dwellings had a creative
      climate, there was a negative process in terms of nurses' well-being with a high
      level of depersonalisation. The residents who displayed a predominant picture of
      negative symptoms were left alone for 84% of the day, and 29.5% of this could be
      explained by their illness. The remainder of the residents' time alone remains
      unexplained.

PMID- 15240090
TI  - The symptom experience of hospitalised Chinese children and adolescents and
      relationship to pre-hospital factors and behaviour problems.
AB  - PURPOSE: To describe the symptom experience of hospitalised Chinese children and
      adolescents and examine the relationship of symptoms to pre-hospital factors and
      child behaviour. METHODS: Data were collected at two hospital sites in Hong Kong
      (HK) and at five hospitals in the Chinese Mainland (CM). A total of 307
      hospitalised children and adolescents (ages 2-18) and their primary caregiver
      (e.g., mother, father or grandparent) participated in the study. Children and
      adolescents completed an age-appropriate symptom diary on one evening and
      subsequent morning early in their hospital stay. Parents completed the diary for
      the children less than 6 years of age. Parents also completed an age-appropriate
      Chinese version of the Child Behaviour Checklist. RESULTS: Over 50% of the
      children and adolescents reported some degree of pain, 75% of them reported
      evening tiredness, and 21% reported gastrointestinal symptoms. The intensity of
      symptoms varied by age and region and symptoms often co-occurred. Greater symptom
      burden was predicted by previous surgery, higher level of worst pain prior to
      hospitalisation, parent report of child behaviour problems, and co-occurrence of
      other symptoms. CONCLUSIONS: Hospitalised Chinese children manifest symptoms of
      pain, tiredness, and gastrointestinal distress that vary based on pre-hospital
      factors and are associated with child behaviour problems. Further research is
      needed to identify causes and treatments for children's symptoms.

PMID- 15240091
TI  - Cross-cultural comparison of workplace stressors, ways of coping and demographic
      characteristics as predictors of physical and mental health among hospital nurses
      in Japan, Thailand, South Korea and the USA (Hawaii).
AB  - In an attempt to cross-culturally compare factors that may contribute to the
      nursing shortage within countries that have produced a limited number of research
      findings on role stress in nurses, this research examined work stressors, ways of
      coping and demographic characteristics as predictors of physical and mental
      health among hospital nurses from Japan, South Korea, Thailand and the USA
      (Hawaii). Subjects (n = 1554 hospital-based nurses) were administered four self
      report questionnaires: Demographic Questionnaire, "Nursing Stress Scale", "Ways
      of Coping Questionnaire" and "SF-36 Health Survey". Findings suggested that
      nurses indicated similar workplace stressors, ways of coping, and levels of
      physical and mental health. While subjects, across countries, demonstrated a
      variety of predictors of physical and mental health, several predictors were
      found to be the same. Cross-culturally the role of nurses may vary; however,
      certain factors are predictive of the status of hospital nurses' physical health
      and mental health.

PMID- 15240092
TI  - The theories underpinning rational emotive behaviour therapy: where's the
      supportive evidence?
AB  - This paper examines the underlying theoretical philosophy of one of the most
      widely used cognitive behaviour therapies, rational emotive behaviour therapy. It
      examines whether two central theoretical principles are supported by research
      evidence: firstly, that irrational beliefs lead to dysfunctional emotions and
      inferences and that rational beliefs lead to functional emotions and inferences
      and, secondly, that demand beliefs are the primary core irrational belief. The
      established criteria for evaluating the efficacy of the theories are detailed and
      used to evaluate the strength of evidence supporting these two assumptions. The
      findings indicate there is limited evidence to support these theories.

PMID- 15240093
TI  - Community health service needs assessment in Korea using OMAHA Classification
      System.
AB  - This study examined the appropriateness of OMAHA Classification System in
      identifying health service needs and relevant strategies for intervention by
      public health nurses working in community health centers in Seoul. The face-to
      face interview using a questionnaire was used to assess individual and family
      health needs in the targeted district. Respondents were 4024 persons from 1449
      households in one municipal district in Seoul, Korea. Based on OCS, 16 problems
      were identified including insufficient income and inadequate living space,
      ineffective communication with community resources, pain, and substance use.
      Health teaching, guidance and counseling, case management, treatment, and
      surveillance were identified as interventions for these problems. These results
      suggest that OCS is appropriate to implement in Korea to plan and organize better
      nursing interventions for community residents by public health nurses working in
      health centers.

PMID- 15240094
TI  - Hormonal regulation of lactate dehydrogenase-A through activation of protein
      kinase C pathways in MCF-7 breast cancer cells.
AB  - Lactate dehydrogenase A (LDH-A) is hormonally regulated in rodents, and increased
      expression of LDH-A is observed during mammary gland tumorigenesis. The
      mechanisms of hormonal regulation of LDH-A were investigated using a series of
      deletion and mutant constructs derived from the rat LDH-A gene promoter. Results
      of these studies show that constructs containing the -92 to -37 region of the LDH
      A promoter are important for basal and E2-induced transactivation, and mutation
      of the consensus CRE motif within this region results in significant loss of
      basal activity and hormone-responsiveness. Gel mobility shift assays using
      nuclear extracts from MCF-7 cells show that both CREB and ATF-1 interact with the
      CRE. Studies with kinase inhibitors show that E2-induced activation of this CRE
      is dependent on protein kinase C, and these data indicate that LDH-A is induced
      through a non-genomic pathway of estrogen action.

PMID- 15240095
TI  - A rapid method of sequencing long synthetic peptide sequences by laser power
      variation in MALDI-ToF, using polyglutamine model peptides.
AB  - Matrix assisted laser desorption ionization-time of flight (MALDI-ToF) has
      evolved into a powerful method for structural analysis of biomolecules. The paper
      reports a very simple and efficient method of sequencing of long peptides using
      long polyglutamine stretches with and without interruptions as model peptides,
      using MALDI-ToF in a linear mode. The method does not require any enzymatic or
      proteolytic digestions and very long synthetic polyglutamine sequences can be
      sequenced efficiently just by incremental variation of laser power. The data also
      reveal whenever there is any interruption within a stretch of glutamines it
      undergoes a very prompt cleavage at that site. Thus, this method provides an
      alternative tool for validating long polyglutamine stretches which are very often
      used as models for studying the structure and conformation of proteins associated
      with a number of neurodegenerative disorders.

PMID- 15240097
TI  - Initiation sites for human DNA replication at a putative ribulose-5-phosphate 3
      epimerase gene.
AB  - Replication of the human genome requires the activation of thousands of replicons
      distributed along each one of the chromosomes. Each replicon contains an
      initiation, or origin, site, at which DNA synthesis begins. However, very little
      information is known about the nature and positioning of these initiation sites
      along human chromosomes. We have recently focused our attention to a 1.1 kb
      region of human chromosome 2 which functioned as an episomal origin in the yeast
      Saccharomyces cerevisiae. This region corresponded to the largest exon of a
      putative ribulose-5-phosphate-3-epimerase gene (RPE). In the present study we
      have used a real-time PCR-based nascent strand DNA abundance assay to map
      initiation sites for DNA replication in in vivo human chromosomes around a 13.4
      kb region encompassing the putative RPE gene. By applying this analysis to a 1
      1.4 kb nascent strand DNA fraction isolated from both normal skin fibroblasts,
      and the breast cell line MCF10; we have identified five initiation sites within
      the 13.4 kb region of chromosome 2. The initiation sites appear to map to similar
      positions in both cell lines and occur outside the coding regions of the putative
      RPE gene.

PMID- 15240096
TI  - Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent
      with tyrosine nitration of insulin receptor substrate-1.
AB  - Inducible nitric oxide synthetase plays an essential role in insulin resistance
      induced by a high-fat diet. The reaction of nitric oxide with superoxide leads to
      the formation of peroxynitrite (ONOO-), which can modify several proteins. In
      this study, we investigated whether peroxynitrite impairs insulin-signalling
      pathway. Our experiments showed that 3-(4-morpholinyl)sydnonimine hydrochloride
      (SIN-1), a constitutive producer of peroxynitrite, dose-dependently inhibited
      insulin-stimulated glucose uptake. While SIN-1 did not affect the insulin
      receptor protein level and tyrosine phosphorylation, it reduced the insulin
      receptor substrate-1 (IRS-1) protein level, and IRS-1 associated
      phosphatidylinositol-3 kinase (PI-3 kinase) activity. Although SIN-1 did not
      induce Ser307 phosphorylation of IRS-1, tyrosine nitration of IRS-1 was detected
      in SIN-1-treated-Rat1 fibroblasts expressing human insulin receptors. Mass
      spectrometry showed that peroxynitrite induced at least four nitrated tyrosine
      residues in rat IRS-1, including Tyr939, which is critical for association of IRS
      1 with the p85 subunit of PI-3 kinase. Our results suggest that peroxynitrite
      reduces the IRS-1 protein level and decreases phosphorylation of IRS-1 concurrent
      with nitration of its tyrosine residues.

PMID- 15240098
TI  - Interaction of ligand-receptor system between stromal-cell-derived factor-1 and
      CXC chemokine receptor 4 in human prostate cancer: a possible predictor of
      metastasis.
AB  - Interaction of ligand-receptor systems between stromal-cell-derived factor-1 (SDF
      1) and CXC chemokine receptor 4 (CXCR4) is closely involved in the organ
      specificity of cancer metastasis. We hypothesized that SDF-1-CXCR4 ligand
      receptor system plays an important role in prostate cancer metastasis. To test
      this hypothesis, expression level of SDF-1 and CXCR4 was analyzed in prostate
      cancer (PC) cell lines (LNCaP, PC3, and DU145) and normal prostate epithelial
      cell line (PrEC). We also performed migration assay and MTT assay to investigate
      the chemotactic effect and growth-promoting effect of SDF-1 on DU145 and PC3
      cells, respectively. Furthermore, we performed immunohistochemical analysis of
      CXCR4 expression in tissues from 35 cases of human prostate cancer. CXCR4
      expression was detected in all three prostate cancer cell lines, but not in
      PrECs. SDF-1 significantly enhanced the migration of PC3 and DU145 cells in a
      dose-dependent manner, and anti-CXCR4 antibody inhibited this chemotactic effect.
      However, SDF-1 itself did not significantly stimulate the cell growth rate of
      prostate cancer cell lines. Positive CXCR4 protein was found in 20 out of 35
      clinical PC samples (57.1%). Three patients with lung metastasis showed
      definitely positive CXCR4 immunostaining. Logistic regression analysis revealed
      that positive expression of CXCR4 protein was an independent and superior
      predictor for bone metastasis to Gleason sum (P < 0.05). Furthermore, among PC
      patients with PSA greater than 20 ng/mL, the positive rate of CXCR4 protein was
      significantly higher in patients with bone metastasis than in those with no bone
      metastasis (P = 0.017). These findings suggest that the interaction between SDF-1
      and CXCR4 ligand-receptor system is involved in the process of PC metastasis by
      the activation of cancer cell migration. This is the first report to investigate
      the role of interaction of ligand-receptor systems between SDF-1 and CXCR4 in
      prostate cancer metastasis.

PMID- 15240100
TI  - Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and
      SAR.
AB  - During screening for the flavonoid chemosensitizers, it was found that
      5,7,3',4',5'-pentamethoxyflavone (PMF) was equipotent to verapamil in vitro with
      respect to the chemosensitizing effect. PMF appears to have a chemosensitizing
      effect not only by increasing the intracellular accumulation of the drugs without
      competition in a binding site of azidopine but also by interfering with the
      substrate-stimulated ATPase activity. Structure-activity relationship suggests
      that methoxylated substitution and its numbers or sites of the rings are more
      important than its hydroxylated counterparts in chemosensitization. Overall, PMF
      is anticipated to be a novel and highly potent second-generation flavonoid
      chemosensitizer because PMF has significant advantages of having a high
      therapeutic index, of being a non-transportable inhibitor, and of having a low
      possibility of drug interactions at the azidopine-binding site of Pgp.

PMID- 15240099
TI  - Isolation and functional characterization of a dynamin-like gene from Plasmodium
      falciparum.
AB  - A novel dynamin-like GTPase gene, Pfdyn1, was cloned from an asexual stage cDNA
      library of Plasmodium falciparum Dd2 strain. Pfdyn1 contains a highly conserved N
      terminal tripartite GTPase domain, a coiled-coil region, and a C-terminal 129 aa
      unknown function domain. Like yeast Vps1p, it lacks pleckstrin homology domain
      and proline-rich region. Western blot analysis showed that Pfdyn1 is a Triton X
      100 insoluble protein expressed only in the mature sub-stage. Morphological
      studies indicated that Pfdyn1 is partly co-localized with PfGRP, a known ER
      resident protein, and localizes diffusely with several membrane structures and a
      60-100 nm vesicle both inside and on surface of the parasites and also in the
      cytoplasm of infected erythrocytes. The dsRNA originated by C-terminus fragment
      of Pfdyn1 inhibits markedly the growth of P. falciparum parasite at the
      erythrocyte stage. Those data showed that Pfdyn1 is a conservative, membrane
      related protein and plays an essential role for the survival of Plasmodium
      parasite.

PMID- 15240101
TI  - Transcriptional regulation of the TGF-beta pseudoreceptor BAMBI by TGF-beta
      signaling.
AB  - BAMBI is a transmembrane glycoprotein related to the transforming growth factor
      beta (TGF-beta)-family type I receptors and functions as a negative regulator of
      TGF-beta signaling during development. BAMBI is induced by BMP signaling through
      the evolutionary conserved BMP-responsive elements in its promoter. Furthermore,
      we have recently shown that Wnt/beta-catenin signaling activates transcription of
      BAMBI and that BAMBI expression is aberrantly elevated in most colorectal
      carcinomas. Here, we show that BAMBI is also directly induced by TGF-beta
      signaling, through the three tandem repeats of 13 bp sequences containing the
      SMAD-binding elements, which are distinct from the BMP-responsive element. Our
      findings suggest that BAMBI transcription is regulated by TGF-beta signaling
      through direct binding of SMAD3 and SMAD4 to the BAMBI promoter.

PMID- 15240102
TI  - Novel inter- and intrasubunit contacts between transport-relevant residues of the
      homodimeric mitochondrial phosphate transport protein.
AB  - Ser158 is located near the middle of the matrix loop connecting transmembrane
      helices C and D of the mitochondrial phosphate transport protein (PTP). The
      mutant Ser158Thr PTP is transport-inactive. His32 is located near the middle of
      transmembrane helix A and Thr79 is located 5 residues away from transmembrane
      helix B and its N-terminal (matrix end). Single site mutant PTPs that have either
      residue replaced with Ala are transport-inactive. Based on the high resolution
      structure of a subunit of the bovine ADP/ATP translocase, on sequence
      similarities between members of the mitochondrial transport protein family, and
      on the PTP subunit/subunit contact site between transmembrane A helices, it is
      now suggested that the Ser158 site is at the PTP subunit/subunit contact site.
      This contact site is essential for keeping the transport cycles catalyzed by the
      two PTP subunits 180 degrees out of phase. The data also suggest that His32 and
      Thr79 of the same subunit interact and couple the phosphate and the proton
      transport paths.

PMID- 15240104
TI  - Rapid preparation of human urine and plasma samples for analysis of F2
      isoprostanes by gas chromatography-mass spectrometry.
AB  - Reliable MS-based methods have been developed for the measurement of free and
      esterified F2-isoprostanes. However, prior to sample analysis several steps of
      purification, including solid-phase extraction followed by TLC or HPLC, are
      usually required, making it tedious to analyze large sample numbers, e.g., for
      population studies. We report a quick sample purification method using anion
      exchange solid phase extraction (SPE), which is highly selective for acidic
      compounds. Urine and hydrolyzed plasma of healthy individuals were acidified
      before SPE extraction, washed with 4 different solvent mixtures and finally
      eluted with ethyl acetate. The eluted samples were first derivatized with
      pentafluorobenzyl bromide followed by a second derivatization with bis
      (trimethylsilyl)trifluoroacetamide. F2-isoprostanes were analyzed by GC-MS-NCI.
      The method was highly sensitive; the limit of detection at 5:1 signal-to-noise
      ratio was 0.037 ng/ml and 0.007 ng/mg creatinine for plasma and urine,
      respectively. Anion exchange SPE extraction for F2-isoprostane showed recovery of
      55-65% and high linearity for concentration 0-1.0 ng/ml for urine (CV=4.08%,
      r2=0.990) and 0-0.5 ng/ml for plasma (CV=4.07%, r2=0.998). Fasting for 6h
      significantly increased plasma F2-isoprostanes levels, which has implications for
      the design of intervention studies using this biomarker.

PMID- 15240103
TI  - Methylglyoxal induces apoptosis through activation of p38 MAPK in rat Schwann
      cells.
AB  - The formation of glucose-derived methylglyoxal (MG), a highly reactive dicarbonyl
      compound, is accelerated under diabetic conditions. We examined whether MG was
      capable of inducing apoptosis in Schwann cells (SCs), since recent studies have
      suggested a potential involvement of apoptotic cell death in the development of
      diabetic neuropathy. MG induced apoptosis in SCs in a dose-dependent manner,
      accompanied by a reduction of intracellular glutathione content and activation of
      the p38 MAPK. Inhibiting the p38 MAPK activation by SB203580 successfully
      suppressed the MG-induced apoptosis in SCs. Aminoguanidine and N-acetyl-L
      cysteine also inhibited the MG-induced p38 MAPK activation and apoptosis along
      with restoration of the intracellular glutathione content. These results suggest
      a potential role for MG in SC injury through oxidative stress-mediated p38 MAPK
      activation under diabetic conditions, and it may serve as a novel insight into
      therapeutic strategies for diabetic neuropathy.

PMID- 15240105
TI  - Fusion of Aequorea victoria GFP and aequorin provides their Ca(2+)-induced
      interaction that results in red shift of GFP absorption and efficient
      bioluminescence energy transfer.
AB  - The bioluminescence emitted by Aequorea victoria jellyfish is greenish while its
      single bioluminescent photoprotein aequorin emits blue light. This phenomenon may
      be explained by a bioluminescence resonance energy transfer (BRET) from aequorin
      chromophore to green fluorescent protein (GFP) co-localized with it. However, a
      slight overlapping of the aequorin bioluminescence spectrum with the GFP
      absorption spectrum and the absence of marked interaction between these proteins
      in vitro pose a question on the mechanism providing the efficient BRET in A.
      victoria. Here we report the in vitro study of BRET between homologous Ca(2+)
      activated photoproteins, aequorin or obelin (Obelia longissima), as
      bioluminescence energy donors, and GFP, as an acceptor. The fusions containing
      donor and acceptor proteins linked by a 19 aa peptide were purified after
      expressing their genes in Escherichia coli cells. It was shown that the GFP
      aequorin fusion has a significantly greater BRET efficiency, compared to the GFP
      obelin fusion. Two main factors responsible for the difference in BRET efficiency
      of these fusions were revealed. First, it is the presence of Ca(2+)-induced
      interaction between the donor and acceptor in the aequorin-containing fusion and
      the absence of the interaction in the obelin-containing fusion. Second, it is a
      red shift of GFP absorption toward better overlapping with aequorin
      bioluminescence induced by the interaction of aequorin with GFP. Since the
      connection of the two proteins in vitro mimics their proximity in vivo, Ca(2+)
      induced interaction between aequorin and GFP may occur in A. victoria jellyfish
      providing efficient BRET in this organism.

PMID- 15240106
TI  - Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF
      induction.
AB  - Bone marrow comprises heterogeneous cell populations, of which certain
      progenitors have demonstrated the ability to differentiate into multiple
      mesenchymal cell lineages. This study demonstrates the bone marrow stromal cells
      (BMSCs) with intrinsic plasticity to differentiate into hepatocyte-like
      phenotypes under in vitro induction of hepatocyte growth factor (HGF). BMSCs
      isolated from rat femurs and tibias were cultured and passaged 3-4 times in the
      presence of HGF. Cells were harvested on days 0, 10, and 20 and subjected to
      examination of any hepatocyte characteristics by flow cytometry, RT-PCR, Western
      blot, and immunocytochemistry. Expression of albumin and alpha-fetoprotein at
      both mRNA and protein levels was detectable on day 10. By contrast, c-Met mRNA
      was significantly decreased in BMSC in the course of HGF induction. Here BMSC was
      shown to differentiate into hepatocyte-like phenotypes given the HGF induction,
      as an alternative source for adult stem cell transplantation in liver repair.

PMID- 15240107
TI  - Mint1, a Munc-18-interacting protein, is expressed in insulin-secreting beta
      cells.
AB  - Munc-18-interacting (Mint) proteins are adaptors involved in regulation of
      synaptic vesicle exocytosis. We have investigated expression and cellular
      localization of Mint1 in pancreatic islets with special reference to insulin
      secreting beta-cells. Western blotting showed that Mint1 was expressed in hamster
      (HIT-T15) and rat (RINm5F) beta-cell lines. Mint1 immunoreactivity was
      preferentially localized to the periphery of individual islet cells. RT-PCR
      analysis revealed that apart from Mint1, RINm5F cells and rat islets also
      transcribed the mRNAs for Mint2 and Mint3. Expression of Mint proteins in
      pancreatic beta-cells suggests a functional role for these proteins in insulin
      granule exocytosis.

PMID- 15240108
TI  - Low- and high-level expressions of heme oxygenase-1 in cultured cells under
      uninduced conditions.
AB  - Heme oxygenase-1 (HO-1) degrades heme into biliverdin, iron, and CO. The enzyme
      participates in adaptive and protective responses to oxidative stress and various
      inflammatory stimuli. We examined the regulation of HO-1 expression in culture
      cells under uninduced conditions. Observations by in situ hybridization and
      immunostaining showed that in cultured mouse fibroblast Balb/3T3 cells not
      subjected to treatment, 10-15% of cells highly expressed HO-1. The similar
      pattern of the expression of HO-1 was observed with mouse embryo liver BNL-CL2
      cells and Chinese hamster ovary cells. The marked expression of HO-1 was related
      to the activation of stress-activated protein kinase and to the expression of
      cyclooxygenase (Cox)-2. When the cells were treated with arachidonic acid, a
      precursor of prostaglandin, induction of HO-1 in the HO-1-expressing cells but
      not in the low-expressing cells occurred. This increase was abrogated by the
      treatment with the Cox inhibitors, indomethacin, and dexamethasone. Neither
      prostaglandin H2, E2 nor F2a induced HO-1 expression. These results suggest that
      some cells respond to the cellular stress and intermediates of prostaglandin
      biosynthesis may act as endogenous stressors to induce HO-1.

PMID- 15240109
TI  - Functional expression of the human breast cancer resistance protein in Pichia
      pastoris.
AB  - We report functional expression of BCRP in Pichia pastoris in which BCRP was
      produced as a 62 kDa underglycosylated protein. BCRP expression level in P.
      pastoris was comparable to that in HEK cells. The basal BCRP ATPase activity in
      the yeast membranes was approximately 40-80 nmol Pi/min/mg protein, which can be
      modulated by known BCRP substrates and inhibitors. Photolabeling of BCRP with 8
      azido[alpha-32P]ATP was dependent preferentially on the presence of Co2+ than
      Mg2+ and could be inhibited by a molar excess of ATP. Vanadate-induced trapping
      of 8-azido[alpha-32P]ADP by BCRP was much more significant in the presence of
      Co2+ than that with Mg2+. The Km and Vmax values of BCRP for [3H]E1S transport
      were 3.6+/-0.3 microM and 55.2+/-1.6 pmol/min/mg protein, respectively. This
      efficient and cost-effective expression system should facilitate large scale
      production and purification of BCRP for further structural and functional
      analyses.

PMID- 15240110
TI  - Cox-2 inhibition abrogates Chlamydia pneumoniae-induced PGE2 and MMP-1
      expression.
AB  - Peripheral blood monocytes (PBMC) promote vascular inflammation and
      atherosclerosis. Chlamydia pneumoniae (Cp) infection of PBMC is found in
      atherosclerotic patients, appears refractory to antibiotics, and may predispose
      to vascular damage. In Cp-infected human PBMC we analyzed the role of
      cyclooxygenase-2 (Cox-2) for the proatherosclerotic key mediators prostaglandin
      E2 (PGE2) and interstitial collagenase (MMP-1). Cp infection resulted in rapid
      and sustained Cox-2 mRNA and protein stimulation depending on p38 and p44/42
      MAPkinases. Subsequent upregulation of PGE synthase and MMP-1 was completely
      abrogated by the selective Cox-2 inhibitor NS398. Enhanced synthesis of PGE2 and
      MMP-1 in Cp infected PBMC is mediated through initiation of the p38 and p44/42
      MAPK pathways and requires sustained Cox-2 activation. Selective Cox-2
      inhibitors, currently under investigation for cardiovascular risk reduction, may
      represent a novel therapeutic option for patients with endovascular Cp infection
      as they target the actuated pathological signal transduction cascade in
      persistently infected PBMC.

PMID- 15240111
TI  - Response of rainbow trout transcriptome to model chemical contaminants.
AB  - We used high-density cDNA microarray in studies of responses of rainbow trout fry
      at sublethal ranges of beta-naphthoflavone, cadmium, carbon tetrachloride, and
      pyrene. The differentially expressed genes were grouped by the functional
      categories of Gene Ontology. Significantly different response to the studied
      compounds was shown by a number of classes, such as cell cycle, apoptosis, signal
      transduction, oxidative stress, subcellular and extracellular structures, protein
      biosynthesis, and modification. Cluster analysis separated responses to the
      contaminants at low and medium doses, whereas at high levels the adaptive
      reactions were masked with general unspecific response to toxicity. We found
      enhanced expression of many mitochondrial proteins as well as genes involved in
      metabolism of metal ions and protein biosynthesis. In parallel, genes related to
      stress and immune response, signal transduction, and nucleotide metabolism were
      down-regulated. We performed computer-assisted analyses of Medline abstracts
      retrieved for each compound, which helped us to indicate the expected and novel
      findings.

PMID- 15240112
TI  - Sphingosine 1-phosphate enhances portal pressure in isolated perfused liver via
      S1P2 with Rho activation.
AB  - Although structural changes are most important to determine vascular resistance
      in portal hypertension, vasoactive mediators also contribute to its regulation.
      Hepatic stellate cells (HSCs) are assumed to play a role in modulating
      intrahepatic vascular resistance based on their residence in the space of Disse
      and capacity to contract. Because sphingosine 1-phosphate (S1P) has been shown to
      stimulate HSC contractility, we wondered if S1P could regulate portal pressure.
      S1P at 0.5-5 microM increased portal pressure in isolated rat perfused liver.
      This effect was abrogated in the presence of a binding antagonist for S1P2, JTE
      013. Perfusion of isolated rat liver with 5 microM S1P increased Rho activity in
      the liver, and co-perfusion with JTE-013 cancelled S1P-induced Rho activation.
      Because S1P is present in human plasma at approximately 0.2 microM, S1P might
      readily regulate portal vascular tone in physiological and pathological status.
      The antagonist for S1P2 merits consideration for treatment of portal
      hypertension.

PMID- 15240113
TI  - Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP.
AB  - Daxx-mediated transcriptional repression was modulated by a speckled POZ domain
      protein SPOP which was first identified as an autoantigen from the serum of a
      scleroderma patient. This is the first report on the biochemical and functional
      interactions between Daxx and SPOP. The COOH-terminal region of Daxx interacts
      with the NH2-terminal region of SPOP. SPOP reversed the transcriptional
      repression mediated by Daxx which binds with ETS1 transcription factor to repress
      ETS1-responsive gene expression. Mutagenesis study suggests that the ability of
      SPOP to self-associate as well as its ability to bind with Daxx was important for
      the modulation of Daxx-mediated transcriptional repression.

PMID- 15240114
TI  - Reduction of SNAP25 in acid secretion defect of Foxl1-/- gastric parietal cells.
AB  - Foxl1 is a winged helix transcription factor expressed in the mesenchyme of the
      gastrointestinal tract. In the absence of Foxl1, parietal cells fail to secrete
      gastric acid in response to various secretagogue stimuli including cAMP. A marked
      decrease in H+,K(+)-ATPase expression was observed even though a substantial
      number of parietal cells still existed in Foxl1-deficient mice. Ultrastructural
      analysis suggested that the gastric acid secretion defect in Foxl1-deficient mice
      is mainly due to impairment in the fusion of cytoplasmic tubulovesicular
      structures to the apical canalicular plasma membrane. Among the molecules
      involved in the membrane fusion event, only SNAP25 showed a significant decrease
      in mRNA expression, which likely caused the impairment in acid secretion from
      parietal cells in Foxl1-deficient mice, with the reduction in H+,K(+)-ATPase
      expression contributing to additional effect.

PMID- 15240115
TI  - Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type
      I diabetes mellitus through activation of JNK.
AB  - 14-3-3 family members are dimeric, phosphoserine binding proteins that regulate
      signal transduction, apoptotic, and checkpoint control pathways. Recently,
      cardiomyocyte apoptosis has been characterized in type I diabetes mellitus. In
      order to study the molecular mechanism underlying diabetes-induced cardiomyocyte
      apoptosis, we examined the role of 14-3-3 protein and MAPK pathways in transgenic
      mice with cardiac specific expression of dominant negative 14-3-3eta (DN-14-3-3).
      p38 MAPK was highly activated 1, 28, and 56 days after diabetes induction by
      streptozotocin, whereas peak JNK activation was found on day 3 and decreased
      afterwards. In contrast, ERK1/2 were not activated in diabetic myocardium.
      Cardiomyocyte apoptosis was peaked on day 3 and decreased on 7, 28, and 56 days.
      p38 MAPK and JNK activation as well as cardiomyocyte apoptosis were greatly
      increased in DN-14-3-3 mice relative to non-transgenic mice. Moreover, we found a
      significant correlation between JNK activation and apoptosis in diabetic
      myocardium. These results indicate for the first time that 14-3-3 protein plays a
      critical anti-apoptotic role in diabetic myocardium by inhibiting the JNK
      pathway.

PMID- 15240116
TI  - In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins.
AB  - We report the first characterization of the in vivo porphyrin scavenging
      abilities of two components of a newly discovered heme scavenging system
      involving iron-regulated surface determinant (Isd) proteins. These proteins are
      present within the cell envelope of the Gram-positive human pathogen
      Staphylococcus aureus. IsdC and IsdE, when expressed heterologously in
      Escherichia coli, efficiently scavenged intracellular heme and resulted in de
      novo heme synthesis in excess of 100-fold above background. Magnetic circular
      dichroism analyses showed that the heme-binding properties of the two proteins
      differ significantly from one another. IsdC bound almost exclusively free-base
      protoporphyrin IX, whereas the IsdE protein was associated with low spin Fe(III)
      and Fe(II) heme. These properties provide important insight into the possible
      mechanisms of iron scavenging from bound heme by Isd proteins.

PMID- 15240117
TI  - Role for PKC-epsilon in neuronal death induced by oxidative stress.
AB  - We investigated which isoforms of PKCs can be modulated and what their roles are
      during l-buthionine-S,R-sulfoximine (BSO)-induced neuronal death. We observed the
      isoform specific translocation of PKC-epsilon from the soluble fraction to the
      particulate in cortical neurons treated with 10 mM BSO. The translocation of PKC
      epsilon by BSO was blocked by antioxidant trolox, suggesting the PKC-epsilon as a
      downstream of reactive oxygen species (ROS) elevated by BSO. Trolox inhibited the
      ROS elevation and the neuronal death in BSO-treated cortical cells. The BSO
      induced neuronal death was remarkably inhibited by both the pharmacological
      inhibition of PKC-epsilon with epsilonV1-2 and the functional blockade for PKC
      epsilon through overexpression of PKC-epsilon V1 region, suggesting the
      detrimental role of PKC-epsilon. These results suggest that PKC-epsilon is the
      major PKC isoform involved in the pathways triggered by ROS, leading to neuronal
      death in BSO-treated cortical neurons.

PMID- 15240118
TI  - Key residues contributing to dominant conformational autoantigenic epitopes on
      thyroid peroxidase identified by mutagenesis.
AB  - Thyroid peroxidase (TPO) is a major autoantigen in thyroid autoimmune disease
      where pathogenic autoantibodies recognise conformational epitopes restricted to
      two overlapping immunodominant regions (IDR) termed IDR-A and -B. Based upon our
      structural model of TPO, we report on the localisation of the IDRs to specific
      amino acids important for autoantibody binding. Using a panel of recombinant
      human Fabs (rhFabs) from autoimmune patients, specific for the IDR-A or -B
      epitopes, in combination with eukaryotic expression of 14 single amino acid
      mutants of TPO, we identify R225 and K627 as key components of IDR-A and -B,
      respectively. Moreover, each mutant specifically led to the loss of binding of
      three different IDR-A- or -B-specific rhFabs, without affecting the binding of
      autoantibodies to the other determinant. Further supportive evidence for the role
      of amino acids R225 and K627 was obtained with murine monoclonal antibodies that
      first defined the IDRs. The identification of amino acids R225 and K627 as key
      residues for the IDR epitopes on TPO will advance our understanding of the
      molecular basis of autoreactivity and facilitate the design of novel therapeutic
      agents.

PMID- 15240119
TI  - Autoantibodies against IA-2, GAD, and topoisomerase II in type 1 diabetic
      patients.
AB  - Prevalence of autoantibodies against IA-2 (IA-2A), glutamic acid decarboxylase
      (GADA), and type II DNA topoisomerase (TopIIA) of Taiwanese type 1 diabetes
      mellitus (T1DM) patients was investigated. Correlations of these autoantibodies
      with patients' clinical manifestations were also analyzed. Prevalence of IA-2A,
      GADA, and TopIIA in our patients was 23.6%, 47.1%, and 55.2%, respectively.
      Eighty percent of the IA-2A recognized the carboxyl terminus of the IA-2 protein
      tyrosine phosphatase-like domain. Average disease duration of IA-2A+ patients was
      significantly shorter than that of IA-2A- patients [3.76+/-0.42 vs. 4.98+/-0.34
      years, p = 0.028]. Presence of GADA was correlated with the mean age of onset
      [10.82+/-0.76 vs. 8.38+/-0.77 years for GADA+ and GADA- patients, p = 0.026].
      Patients with adolescent onset have higher GADA prevalence and better residual
      beta-cell functions. TopIIA and GADA are suggested to be better markers for
      Taiwanese T1DM patients because of their higher prevalence and persistence.

PMID- 15240120
TI  - D-galactosyl-beta1-1'-sphingosine and D-glucosyl-beta1-1'-sphingosine induce
      human natural killer cell apoptosis.
AB  - Natural killer (NK) cells perform multiple biological functions including tumor
      cell lysis and eradicating virally infected cells. Here, we report for the first
      time that D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1- 1' sphingosine
      damage human NK cells. We show that these cells express T-cell-associated gene-8,
      the receptor for glycosphingolipids. D-galactosyl-beta1-1' sphingosine and D
      glucosyl-beta1-1' sphingosine induce the in vitro chemotaxis of human NK cells.
      Both D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1-1' sphingosine
      inhibit the cytotoxicity and IFN-gamma secretion by these cells. Further analysis
      shows that the glycosphingolipids D-galactosyl-beta1-1' sphingosine and D
      glucosyl-beta1-1' sphingosine but not any other lipid examined, which include D
      lactosyl-beta1-1' sphingosine, sphingosine 1-phosphate, sphingosine,
      lysophosphatidic acid, and phosphatidic acid, induce the apoptosis, globoid-like
      formation, and multinucleation in human NK cells. These results may have
      important implications on diseases where glycosphingolipids accumulate.

PMID- 15240121
TI  - Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through
      the inactivation of transcriptional factors of AP-1 and NF-kappaB.
AB  - Helicobacter pylori infection leads to significant inflammations in the gastric
      mucosa, which is closely associated with development of gastric cancer. Heat
      shock protein 90 (HSP 90) has been revealed to be critical for intracellular
      signaling that participates in inflammatory response as well as carcinogenesis.
      In this study, we investigated a regulatory role of HSP 90 in H. pylori-induced
      IL-8 production. Our results showed that H. pylori stimulated significant
      phosphorylation of HSP 90 and the phosphorylation was diminished by
      administration of HSP 90 inhibitor, geldanamycin (GA). Treatment of GA completely
      inhibited H. pylori-induced IL-8 production due to deactivation of ERK1/2 and NF
      kappaB. These results subsequently lead to inactivation of AP-1 and NF-kappaB,
      which are known to be major transcriptional factors of IL-8. Our data provide
      important insights that HSP 90 is involved as a crucial regulator in H. pylori
      induced IL-8 production and its inhibitor could be potentially used for the
      inhibition of H. pylori-provoked inflammation.

PMID- 15240122
TI  - Mechanisms of cross-resistance between nucleoside analogues and vincristine or
      daunorubicin in leukemic cells.
AB  - The aim of this study was to clarify the biochemical and molecular mechanisms
      behind the cross-resistance to nucleoside analogues (NAs) in four erythroleukemic
      cell lines with acquired resistance to the anthracycline daunorubicin and to the
      vinca alkaloid vincristine, expressing high levels of p-glycoprotein (P-gp,
      MDR1). All resistant strains exhibited cross-resistance to NA (cladribine and
      cytosine arabinoside)-induced apoptosis, assessed by caspase-3-like activation
      and were less sensitive to NA cytotoxicity in MTT assay. Real-time PCR and enzyme
      activity analysis showed reduced amounts of deoxycytidine kinase (35-80%) and
      elevated levels of 5'-nucleotidases (50-100%). The ratio 5'-nucleotidase to
      deoxycytidine kinase increased between 2.5- and 7.5-folds in resistant cells.
      This is in agreement with the observation that 5'-nucleotidase/deoxycytidine
      kinase ratio might be an important factor in predicting resistance to NAs.
      Implications of this finding for combining anthracyclines or vinca alkaloids with
      NAs toward leukemic cells are discussed.

PMID- 15240123
TI  - Properties of catalase-peroxidase lacking its C-terminal domain.
AB  - Catalase-peroxidases have a two-domain structure. The N-terminal domain contains
      the bifunctional active site, but the function of the C-terminal domain is
      unknown. We produced catalase-peroxidase containing only its N-terminal domain
      (KatG(Nterm)). Removal of the C-terminal domain did not result in unexpected
      changes in secondary structure as evaluated by CD, but KatG(Nterm) had neither
      catalase nor peroxidase activity. Partial recovery of both activities was
      achieved by incubating KatG(Nterm) with the separately expressed and isolated
      KatG C-terminal domain. Spectroscopic measurements revealed a shift in heme
      environment from a mixture of high-spin species (wtKatG) to exclusively
      hexacoordinate, low-spin (KatG(Nterm)). Moreover, a > 1000-fold lower kon for CN-
      binding was observed for KatG(Nterm). EPR spectra for KatG(Nterm) and the results
      of site-specific substitution of active site histidines suggested that the distal
      histidine was the sixth ligand. Thus, one important role for the C-terminal
      domain may be to support the architecture of the active site, preventing heme
      ligation by this catalytically essential residue.

PMID- 15240124
TI  - Definitive evidence for Ufd2-catalyzed elongation of the ubiquitin chain through
      Lys48 linkage.
AB  - Saccharomyces cerevisiae Ufd2 is a ubiquitin chain elongation factor in the
      ubiquitin fusion degradation (UFD) pathway and functions in stress tolerance. A
      recent study has suggested that the mammalian Ufd2 homologue UFD2a catalyzes
      formation of Lys27- and Lys33-linked polyubiquitin chains rather than the Lys48
      linked chain, but the linkage type of the polyubiquitin chain formed by yeast
      Ufd2 remains unclear. To determine the property of Ufd2, we reconstituted the UFD
      pathway using purified enzymes from yeast. Direct determination of the ubiquitin
      chain linkage type in polyubiquitinated UFD substrates by MALDI-TOF mass
      spectrometry revealed that Ufd2 catalyzes elongation of the ubiquitin chain
      through Lys48 linkage.

PMID- 15240125
TI  - Low pKa lysine residues at the active site of sarcosine oxidase from
      Corynebacterium sp. U-96.
AB  - Sarcosine oxidase from Corynebacterium sp. U-96 is inactivated by iodoacetamide
      with the modification of two specific residues. Comparing the amino acid sequence
      and mass spectra of the peptide fragments containing the modified residues with
      those from the native enzyme, the modified residues were identified to be lysine.
      The pKa of these residues were estimated to be 8.5 and 6.7 from the pH dependence
      of inactivation in the presence and absence of the competitive inhibitor,
      acetate. These estimated pKa values are much lower than that of the epsilon-amino
      group of lysine residue. There may be unique microenvironments around these
      residues that activate their -amino groups to be susceptible to iodoacetamide. A
      possible role of the lysine residue with pKa 6.7 is discussed.

PMID- 15240126
TI  - Proteome analysis by bio-active ceramic water in rat liver: contribution to
      antioxidant enzyme expression, SOD I.
AB  - The purpose of this study was to investigate the protective effect of bio-active
      ceramic water on rat liver. Male Wistar rats were divided into 4 groups of 15
      animals each. Groups 1 and 2 were fed bio-active ceramic water and tap water for
      4 months, respectively. Groups 3 and 4 were treated with the same condition for
      12 months. The changes of protein expression of these four groups were
      investigated using two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. Eleven proteins were
      significantly up-regulated in bio-active ceramic water treated rat liver
      including aldehyde dehydrogenase I and II, albumin, fructose-1,6-bisphosphatase,
      and superoxide dismutase I (SOD I). The most highly expressed protein, SOD I with
      up-regulated enzyme activity, was confirmed by immunoblots as a major antioxidant
      capable of detoxifying normally generated reactive oxygen species. These data
      suggest that modified protein expression of the liver contributes to enhance
      liver function.

PMID- 15240127
TI  - Functional expression and characterization of the human ABCG1 and ABCG4 proteins:
      indications for heterodimerization.
AB  - The closely related human ABC half-transporters, ABCG1 and ABCG4, have been
      suggested to play an important role in cellular lipid/sterol regulation but no
      experimental data for their expression or function are available. We expressed
      ABCG1 and ABCG4 and their catalytic site mutant variants in insect cells,
      generated specific antibodies, and analyzed their function in isolated membrane
      preparations. ABCG1 had a high basal ATPase activity, further stimulated by
      lipophilic cations and significantly inhibited by cyclosporin A, thyroxine or
      benzamil. ABCG4 had a lower basal ATPase activity which was not modulated by any
      of the tested compounds. The catalytic site (K-M) mutants had no ATPase activity.
      Since dimerization is a requirement for half-transporters, we suggest that both
      ABCG1 and ABCG4 function as homodimers. Importantly, we also found that co
      expression of the ABCG4-KM mutant selectively abolished the ATPase activity of
      the ABCG1 and therefore they most probably also heterodimerize. The heterologous
      expression, specific recognition, and functional characterization of these
      transporters should help to delineate their physiological role and mechanism of
      action.

PMID- 15240128
TI  - Overexpression of caveolin-1 increases plasma membrane fluidity and reduces P
      glycoprotein function in Hs578T/Dox.
AB  - Cholesterol is a key lipid in mediating the enzyme activity or signaling pathway
      of many proteins on the plasma membrane in mammalian cells. In this report, we
      demonstrate for the first time that after overexpressing caveolin-1, the plasma
      membrane cholesterol level was decreased by about 12% and 30% for doxorubicin
      sensitive and doxorubicin-resistant Hs578T breast cancer cells, respectively.
      However, the total cholesterol level in both cell lines was increased by about
      10%. By measuring fluorescence and flow cytometry using the fluorescence dyes 1,6
      diphenyl-1,3,5-hexatriene and Merocyanine 540, we found that overexpressing
      caveolin-1 resulted in a similar increase in membrane fluidity and loosening of
      lipid packing density as cholesterol depletion by 1 mM methyl-beta-cyclodextrin
      (MbetaCD) or 2-hydroxypropyl-beta-cyclodextrin (HbetaCD). Moreover, we found that
      the transport activity of P-gp was significantly inhibited by 1 mM MbetaCD or
      HbetaCD, which is also similar to the inhibitory effect of caveolin-1
      overexpression. Our data demonstrate for the first time that the reduction of the
      plasma membrane cholesterol level induced by overexpressing caveolin-1 may
      indirectly inhibit P-gp transport activity by increasing plasma membrane
      fluidity.

PMID- 15240129
TI  - NSAIDs activate PTEN and other phosphatases in human colon cancer cells: novel
      mechanism for chemopreventive action of NSAIDs.
AB  - Studies on chemoprevention of colorectal cancer have generated increasing
      interest. The mechanisms involved in NSAIDs chemopreventive action are not fully
      elucidated. In this study, we examined in human colon cancer cells the effect of
      indomethacin and NS-398 (a pre-clinical selective COX-2 inhibitor) on expression
      of 96 genes of the EGF/PDGF signaling pathways essential for cell proliferation,
      migration, and survival. We found that indomethacin and NS-398 treatment
      significantly upregulated expression of the tumor suppressor gene, PTEN, the MAP
      kinase phosphatase-3, MKP-3, and the protein tyrosine phosphatase, SHP2.
      Additionally, NS-398 treatment increased expression of apoptotic genes such as
      BAD, STAT1, and CASP3. These results suggest that as a consequence of increased
      expression of phosphatases such as PTEN and the resulting dephosphorylation of
      kinases, NSAIDs can negatively regulate the EGF/PDGF pathways in colon cancer
      cells-a novel mechanism for NSAIDs' chemopreventive actions.

PMID- 15240130
TI  - Bcl-2 protects against Abeta(25-35)-induced oxidative PC12 cell death by
      potentiation of antioxidant capacity.
AB  - A substantial body of data indicates that reactive oxygen intermediates (ROIs)
      are implicated in pathogenesis of diverse human diseases. Oxidative stress
      induced by ROIs often causes cell death via apoptosis that is regulated by a
      plenty of functional genes and their protein products. Bcl-2 is one such protein
      that blocks apoptosis induced by various death stimuli. In spite of extensive
      research, the molecular mechanisms underlying antiapoptotic function of Bcl-2 are
      not fully clarified. In the present work, we have investigated the role of bcl-2
      in protecting against beta-amyloid (Abeta)-induced oxidative death in rat
      pheochromocytoma (PC12) cells. Transfection with the antiapoptotic bcl-2 gene
      rescued PC12 cells from apoptotic death induced by Abeta. Addition of an NF
      kappaB inhibitor, such as pyrrolidine dithiocarbamate or N-tosyl-l-phenylalanine
      chloromethyl ketone, to the media aggravated Abeta-induced PC12 cell death. PC12
      cells overexpressing bcl-2 exhibited higher levels of constitutively activated NF
      kappaB compared with vector-transfected controls, which appear to be mediated by
      the elevated activation of Akt/protein kinase B. The ectopic expression of bcl-2
      enhanced both the expression and the activity of catalase, which were attenuated
      by NF-kappaB blockers. These results suggest that NF-kappaB plays a role in bcl-2
      mediated protection against Abeta-induced apoptosis in PC12 cells through
      augmentation of cellular antioxidant capacity.

PMID- 15240131
TI  - Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in
      cerebrovascular endothelial cells.
AB  - Cadmium (Cd), a ubiquitous heavy metal, has been shown to accumulate in the
      central nervous system, especially outside of the blood-brain barrier (BBB),
      suggesting a potential toxicity to nervous tissue. Thus, we investigated the
      effect of Cd on intercellular adhesion molecule-1 (ICAM-1) expression, as an
      indicator of BBB injury, in mouse brain microvessel endothelial cells (bEnd.3
      cells). The treatment with Cd increased the expression of ICAM-1 at the levels of
      protein and mRNA, and these increases were almost completely inhibited by a
      specific NF-kappaB inhibitor SN50. The treatment with Cd induced the
      translocation of NF-kappaB from cytosolic to membrane fraction and increased DNA
      binding activity of NF-kappaB, and this NF-kappaB activation was inhibited by
      SN50. Interestingly, Cd did not trigger the degradation of IkappaBalpha,
      suggesting that Cd-induced ICAM-1 expression is mediated through IkappaBalpha
      degradation-independent pathway. Instead, tyrosine phosphorylation of
      IkappaBalpha was significantly elevated by Cd treatment, and this elevation was
      blocked by genistein, a protein tyrosine kinase inhibitor. In summary, the
      present results suggest that Cd stimulates the expression of ICAM-1 in bEnd.3
      cells, via NF-kappaB activation that is mediated by the tyrosine phosphorylation
      of IkappaBalpha.

PMID- 15240132
TI  - Use of sequence microdivergence in mycobacterial ortholog to analyze
      contributions of the water-activating loop histidine of Escherichia coli uracil
      DNA glycosylase in reactant binding and catalysis.
AB  - Uracil-DNA glycosylase (Ung), a DNA repair enzyme, pioneers uracil excision
      repair pathway. Structural determinations and mutational analyses of the Ung
      class of proteins have greatly facilitated our understanding of the mechanism of
      uracil excision from DNA. More recently, a hybrid quantum-mechanical/molecular
      mechanical analysis revealed that while the histidine (H67 in EcoUng) of the
      GQDPYH motif (omega loop) in the active site pocket is important in positioning
      the reactants, it makes an unfavorable energetic contribution (penalty) in
      achieving the transition state intermediate. Mutational analysis of this
      histidine is unavailable from any of the Ung class of proteins. A complication in
      demonstrating negative role of a residue, especially when located within the
      active site pocket, is that the mutants with enhanced activity are rarely
      obtained. Interestingly, unlike the most Ung proteins, the H67 equivalent in the
      omega loop in mycobacterial Ung is represented by P67. Exploiting this natural
      diversity to maintain structural integrity of the active site, we transplanted an
      H67P mutation in EcoUng. Uracil inhibition assays and binding of a proteinaceous
      inhibitor, Ugi (a transition state substrate mimic), with the mutant (H67P)
      revealed that its active site pocket was not perturbed. The catalytic efficiency
      (Vmax/Km) of the mutant was similar to that of the wild type Ung. However, the
      mutant showed increased Km and Vmax. Together with the data from a double
      mutation H67P/G68T, these observations provide the first biochemical evidence for
      the proposed diverse roles of H67 in catalysis by Ung.

PMID- 15240133
TI  - Substitution of aspartic acid with glutamic acid increases the unfolding
      transition temperature of a protein.
AB  - Proteins from thermophiles are more stable than those from mesophiles. Several
      factors have been suggested as causes for this greater stability, but no general
      rule has been found. The amino acid composition of thermophile proteins indicates
      that the content of polar amino acids such as Asn, Gln, Ser, and Thr is lower,
      and that of charged amino acids such as Arg, Glu, and Lys is higher than in
      mesophile proteins. Among charged amino acids, however, the content of Asp is
      even lower in thermophile proteins than in mesophile proteins. To investigate the
      reasons for the lower occurrence of Asp compared to Glu in thermophile proteins,
      Glu was substituted with Asp in a hyperthermophile protein, MjTRX, and Asp was
      substituted with Glu in a mesophile protein, ETRX. Each substitution of Glu with
      Asp decreased the Tm of MjTRX by about 2 degrees C, while each substitution of
      Asp with Glu increased the Tm of ETRX by about 1.5 degrees C. The change of Tm
      destabilizes the MjTRX by 0.55 kcal/mol and stabilizes the ETRX by 0.45 kcal/mol
      in free energy.

PMID- 15240134
TI  - Molecular and cellular events at the site of myocardial infarction: from the
      perspective of rebuilding myocardial tissue.
AB  - The potential for bone marrow-derived progenitor cells (BMDPC) to regenerate
      myocardial tissue following infarction depends on homing, migration, nourishment,
      and spatially appropriate growth of BMDPC. Requisite to these objectives is the
      expression of adhesion molecules (ICAM-1) and chemoattractant cytokines (MCP-1),
      matrix metalloproteinase (MMP) activity, a neovasculature, and fibrillar collagen
      scaffolding. We found that enhanced ICAM-l and MCP-1, as well as MMP activity on
      day 3 and 7 postMI, are present to facilitate the homing, chemotaxis, and
      migration of circulating cells into the infarct site. The vascular network formed
      at the infarct site contains a ratio of conduit to exchange vessels that is
      greater than that for control tissue and therefore its ability to nourish BMDPC
      for their growth appears to be tenuous. These findings, together with the dense
      formation of a fibrillar collagen scar beyond week 2, suggest the optimal time to
      rebuild myocardium from BMDPC resides within 2 week postMI.

PMID- 15240135
TI  - Growth factor combination for chondrogenic induction from human mesenchymal stem
      cell.
AB  - During the last decade, many strategies for cartilage engineering have been
      emerging. Stem cell induction is one of the possible approaches for cartilage
      engineering. The mesenchymal stem cells (MSCs) with their pluripotency and
      availability have been demonstrated to be an attractive cell source. It needs the
      stimulation with cell growth factors to make the multipluripotent MSCs
      differentiate into chondrogenic lineage. We have shown particular patterns of in
      vitro chondrogenesis induction on human bone marrow MSCs (hBMSCs) by cycling the
      growth factors. The pellet cultures of hBMSCs were prepared for chondrogenic
      induction. Growth factors: TGF-beta3, BMP-6, and IGF-1 were used in combination
      for cell induction. Gene expression, histology, immunohistology, and real-time
      PCR methods were measured on days 21 after cell induction. As shown by histology
      and immunohistology, the induced cells have shown the feature of chondrocytes in
      their morphology and extracellular matrix in both inducing patterns of
      combination and cycling induction. Moreover, the real-time PCR assay has shown
      the expression of gene markers of chondrogenesis, collagen type II and aggrecan.
      This study has demonstrated that cartilage tissue can be created from bone marrow
      mesenchymal stem cells. Interestingly, the combined growth factors TGF-beta3 and
      BMP-6 or TGF-beta3 and IGF-1 were more effective for chondrogenesis induction as
      shown by the real-time PCR assay. The combination of these growth factors may be
      the important key for in vitro chondrogenesis induction.

PMID- 15240136
TI  - Expression cloning of oligomerization-activated genes with cell-proliferating
      potency by pseudotype retrovirus vector.
AB  - We developed a method of clone proliferation promoting fusion genes whose
      proteins were activated by protein oligomerization through the helix-loop-helix
      region (PNT domain) of TEL. We inserted a cDNA library downstream of the PNT
      domain with a retrovirus vector. The resulting retrovirus infected cytokine
      dependent 32D cells and cells with cytokine-independent growth were analyzed for
      the inserted cDNA. We cloned 25 independent fusion genes including seven kinds of
      partner genes. Six of the seven were a fusion of TEL with protein tyrosine
      kinase, LYN, HCK, FGR, SYK, FLT3, and TYK2. A serine/threonine kinase, ARAF1, was
      also found to fuse with TEL. These kinase fusion proteins included kinase domains
      with proper reading frames. These fusions may be a useful model for clarifying
      the downstream signal transduction of constitutive active kinase and this
      expression cloning method may provide a new tool with which to study cell
      proliferation signalling.

PMID- 15240137
TI  - Functional redundancy of the human CCL4 and CCL4L1 chemokine genes.
AB  - CCL4 and CCL4L1 are two CC chemokine genes located at chromosome 17q21 whose
      mature proteins differ at only a single amino acid. Abundant functional
      information exists for CCL4, however, CCL4L1 has only recently been recognized as
      a distinct gene, thus information describing it is wanting. The CCL4L1 protein
      was synthesized in Escherichia coli and compared with the CCL4 protein.
      Competitive binding studies using HEK-293/CCR5 cells produced comparable EC50
      values for the two proteins. Similarly, chemotaxis assays with cells expressing
      CCR1, CCR3, or CCR5 revealed no substantial differences. CCL4L1 was somewhat more
      effective at inhibiting HIV-1 replication in PBMCs than was CCL4, however the
      difference was not statistically significant. These data combined with the
      observation of individual variation in CCL4L1 gene copy number [Eur. J. Immunol.
      32 (2002) 3016, Genomics 83 (2004) 735] support the contention that the CCL4 and
      CCL4L1 proteins have redundant functions.

PMID- 15240138
TI  - Inhibition of phosphatidylinositol 3'-kinase induces preferentially killing of
      PTEN-null T leukemias through AKT pathway.
AB  - We examined the functional role of the phosphatidylinositol 3'-kinase pathway in
      the growth and survival of cell lines of T-cell origin. Pharmacological
      inhibition of PI3'-kinase using LY294002 resulted in apoptosis of acute
      lymphoblastic T-cell leukemia (T-ALL) cell lines including CEM, Jurkat, and MOLT
      4. On the other hand, the cutaneous T-cell lymphoma cell line HUT-78 was found to
      be refractory to LY294002- inducible apoptosis. Sensitivity or resistance to
      pharmacological inhibitors of PI3'-kinase correlated with tumor suppressor PTEN
      gene expression, as sensitive T-ALL cells do not express PTEN and have high level
      of activated AKT, in contrast to HUT-78 cells. Our data demonstrate that
      inhibition of PI3'-kinase results in dephosphorylation of AKT and partial
      inhibition of Bcl-xL expression in T-ALL cells, but not in HUT-78 cells.
      Interestingly, HUT-78 cells were also found to express higher levels of Bcl-xL
      protein as compared to T-ALL cells. Inhibition of PI3'-kinase also induces
      release of cytochrome c from mitochondria and activation of caspase-3 and PARP in
      all T-ALL cell lines tested, but not in HUT-78 cells. Taken altogether, our data
      demonstrate that the PI3'-kinase/AKT pathway plays a major role in the growth and
      survival of PTEN-null T-ALL cells, and identify this cascade as promising target
      for therapeutic intervention in acute T-cell leukemias.

PMID- 15240139
TI  - Recovery of the oxidative activity of caged bovine haemoglobin after UV
      photolysis.
AB  - Caging of bovine haemoglobin with increasing amounts of 1-(2-nitrophenyl)ethyl
      (NPE) and uncaging after a 366 nm irradiation was examined. Caged and photolysed
      conjugates were characterised by enzymatic assay of the ABTS oxidation, UV/Vis
      absorbance, and electrospray mass ionisation. Modification of haemoglobin with
      50, 75, and 100 equivalents of 1-(2-nitrophenyl)diazoethane led to a progressive
      decrease of enzymatic activity. Photolysis at 366 nm during 5, 15, and 30 min
      induced the recovery of a part of the enzymatic activity. ESI analyses showed
      that a reversible binding of up to 6 NPE groups per alpha-chain and that the
      removal of most of the photolabile groups occurred rapidly after 5 min of
      illumination at 366 nm and reached near completion after 15 min. A variable
      alteration of haemoglobin after labelling could explain that the complete removal
      of NPE groups did not restore its full oxidative activity.

PMID- 15240140
TI  - Ectopic expression of von Hippel-Lindau tumor suppressor induces apoptosis in 786
      O renal cell carcinoma cells and regresses tumor growth of 786-O cells in nude
      mouse.
AB  - The von Hippel-Lindau (VHL) is a known tumor suppressor that binds to alpha
      subunits of hypoxia-inducible factors and induces ubiquitin-mediated degradation
      of the protein in an oxygen-dependent manner. VHL is also involved in the
      regulation of tumor angiogenesis, glycolysis, cell cycle regulation, and
      apoptosis. In the present study, we showed that ectopic expression of VHL induces
      apoptosis in renal cell carcinoma 786-O cells which contain only the mutant VHL,
      evidenced by TUNEL assay and DAPI staining. Furthermore, biochemical studies
      indicated that expression of VHL in 786-O cells results in both PARP and CPP32
      cleavage, suggesting that VHL-induced apoptosis in 786-O cells is caspase
      dependent. Moreover, we also observed that apoptosis induced by ectopic VHL
      expression was associated with up-regulation of p27 as well as Bax, implicating
      the roles of these two proteins in VHL-induced apoptosis. The up-regulation of
      p27 and Bax by VHL was specific since we did not detect any changes in the level
      of other apoptotic factors including Fas and Bcl2 by the expression of VHL. We
      next examined the effect of VHL expression on the tumor growth of 786-O renal
      cell carcinoma cells in nude mouse. The results showed that injection of Ad.VHL
      adenovirus regresses the tumor growth of 786-O cells in nude mouse. The analysis
      by TUNEL assay as well as DAPI staining of 786-O tumors injected with Ad.VHL
      showed clear evidence of apoptosis. These results suggest that ectopic VHL
      expression induces apoptotic response in 786-O VHL mutant cells both in vitro and
      in vivo.

PMID- 15240141
TI  - SIRF--a novel regulator element controlling transcription from the p55Cdc/Fizzy
      promoter during the cell cycle.
AB  - p55Cdc proteins participate in activation and timing of ubiquitin ligation by
      APC/C. Labeling of the substrates with ubiquitin leads to degradation of the cell
      cycle proteins through the proteasome in mitosis. Consistent with the phase in
      which the protein functions p55Cdc mRNA is expressed during the cell cycle
      starting in S phase with a maximum in G2/M. We analyzed the human p55Cdc promoter
      responsible for this expression pattern and found with SIRF (Cell-Cycle Site
      Regulating p55Cdc/Fizzy-Transcription) a novel element which downregulates
      transcription in a cell cycle-dependent manner. Activation of gene transcription
      is independent of the SIRF element and NF-Y. The nucleotide sequence of SIRF is
      essentially identical in human, rat, and mouse p55Cdc whereas other parts of the
      promoter are not conserved. SIRF requires its natural promoter context for its
      regulatory function. With a length of 44 nucleotides this element is unusually
      long and may require a large protein complex for its regulation.

PMID- 15240142
TI  - Amphidinolide H, a novel type of actin-stabilizing agent isolated from
      dinoflagellate.
AB  - The effect of novel cytotoxic marine macrolide, amphidinolide H (Amp-H), on actin
      dynamics was investigated in vitro. Amp-H attenuated actin depolymerization
      induced by diluting F-actin. This effect remained after washing out of unbound
      Amp-H by filtration. In the presence of either Amp-H or phalloidin, lag phase,
      which is the rate-limiting step of actin polymerization, was shortened.
      Phalloidin decreased the polymerization-rate whereas Amp-H did not. Meanwhile,
      the effects of both compounds were the same when barbed end of actin was capped
      by cytochalasin D. Quartz crystal microbalance system revealed interaction of Amp
      H with G-actin and F-actin. Amp-H also enhanced the binding of phalloidin to F
      actin. We concluded that Amp-H stabilizes actin in a different manner from that
      of phalloidin and serves as a novel pharmacological tool for analyzing actin
      mediated cell function.

PMID- 15240143
TI  - Interaction of a Mycobacterium tuberculosis repetitive DNA sequence with
      eukaryotic proteins.
AB  - Mycobacterium tuberculosis infects one-third of the world's population and causes
      two million deaths annually. Its intracellular residence raises the possibility
      that bacterial nucleic acids might interact with key host proteins and contribute
      to the pathophysiology of infection. To test this hypothesis, we searched for
      motifs closely resembling eukaryotic transcription factor binding sites in the M.
      tuberculosis H37Rv genome and found activator protein-2 and zinc finger protein-5
      binding motifs in a 36-nucleotide repetitive mycobacterial DNA sequence (RPT1).
      RPT1 bound specifically to nuclear extract proteins from U937, A549, and HeLa
      cells in electrophoretic mobility shift assays but not to activator protein-2.
      Several nuclear and cytosolic proteins showing at least partial binding
      specificity for RPT1 were isolated from U937 and A549 cells by pull-down assays,
      including Ku70 (DNA-dependent protein kinase subunit) and poly(ADP-ribose)
      polymerase-1. RPT1 also specifically activated DNA-dependent protein
      phosphorylation. These results suggest that mycobacterial nucleic acid fragments
      may interact specifically with eukaryotic regulatory proteins which might
      contribute to bacterial life-cycle maintenance.

PMID- 15240144
TI  - Detection and characterization of an acid-induced folding intermediate of
      endostatin.
AB  - Endostatin, an important angiogenesis inhibitor, is very acid resistant. We are
      particularly interested in knowing that whether or not endostatin can form a
      folding intermediate during acid titration. 1H-NMR, CD spectrum, and ANS binding
      assay show that endostatin at pH 2.0 contains little tertiary structure, but
      retains substantial secondary structure with strong ANS binding, and Na2SO4 or
      TFE is found to strongly stabilize endostatin at pH 2.0. All these observations
      are consistent with the formation of a folding intermediate at pH 2.0. Kinetics
      studies show that sulfate anions significantly slow down the process for
      endostatin to reach its equilibrium state at pH 2.0. A regular increase in the
      amount of alpha-helix content of the intermediate of endostatin at pH 2.0 is
      found when the concentration of TFE is increased in the range of 0-40%,
      suggesting that endostatin has an intrinsic alpha-helical propensity.

PMID- 15240145
TI  - Molecular models for shikimate pathway enzymes of Xylella fastidiosa.
AB  - The Xylella fastidiosa is a bacterium that is the cause of citrus variegated
      chlorosis (CVC). The shikimate pathway is of pivotal importance for production of
      a plethora of aromatic compounds in plants, bacteria, and fungi. Putative
      structural differences in the enzymes from the shikimate pathway, between the
      proteins of bacterial origin and those of plants, could be used for the
      development of a drug for the control of CVC. However, inhibitors for shikimate
      pathway enzymes should have high specificity for X. fastidiosa enzymes, since
      they are also present in plants. In order to pave the way for structural and
      functional efforts towards antimicrobial agent development, here we describe the
      molecular modeling of seven enzymes of the shikimate pathway of X. fastidiosa.
      The structural models of shikimate pathway enzymes, complexed with inhibitors,
      strongly indicate that the previously identified inhibitors may also inhibit the
      X. fastidiosa enzymes.

PMID- 15240146
TI  - Aspirin inhibits serine phosphorylation of IRS-1 in muscle and adipose tissue of
      septic rats.
AB  - Whole body insulin resistance has been demonstrated in septic patients and in
      infected animals. In this study, we demonstrate that sepsis induces insulin
      resistance and that pretreatment with aspirin inhibits sepsis-induced insulin
      resistance. Sepsis was observed to lead to serine phosphorylation of IRS-1, a
      phenomenon which was reversed by aspirin in muscle and WAT, in parallel with a
      reduction in JNK activity. In addition, our data show an impairment of insulin
      activation of IR and IRS-1 tyrosine phosphorylation in septic rats and,
      consistent with the reduction of IRS-1 serine phosphorylation observed in septic
      animals pretreated with aspirin, there was an increase in IRS-1 protein levels
      and tyrosine phosphorylation in muscle and WAT. Overall, these results provide
      important new insights into the mechanism of sepsis-induced insulin resistance.

PMID- 15240147
TI  - Prolonged liver-specific transgene expression by a non-primate lentiviral vector.
AB  - Liver-directed gene therapy has the potential for treatment of numerous inherited
      diseases affecting metabolic functions. The aim of this study was to evaluate
      gene expression in hepatocytes using feline immunodeficiency virus-based
      lentiviral vectors, which may be potentially safer than those based on human
      immunodeficiency virus. In vitro studies revealed that gene expression was stable
      for up to 24 days post-transduction and integration into the host cell genome was
      suggested by Alu PCR and Southern blot analyses. Systemic in vivo administration
      of viral particles by the hydrodynamics method resulted in high levels of gene
      expression exclusively in the liver for over 7 months whereas injection of
      plasmid DNA by the same method led to transient expression levels. Our studies
      suggest that feline immunodeficiency-based lentiviral vectors specifically
      transduce liver cells and may be used as a novel vehicle of gene delivery for
      treatment of metabolic disease.

PMID- 15240148
TI  - SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins
      2,5-OAS and MxA.
AB  - Although the use of IFN-alpha in combination with ribavirin has improved the
      treatment efficacy of chronic hepatitis C virus (HCV) infection, 20-50% of
      patients still fail to eradicate the virus depending on the HCV genotype.
      Recently, overexpression of HCV core protein has been shown to inhibit IFN
      signaling and induce SOCS-3 expression. Aim of this study was to examine the
      putative role of SOCS proteins in IFN resistance. By Western blot analysis, a 4
      fold induction of STAT-1/3 phosphorylation by IFN-alpha was observed in mock
      transfected HepG2 clones. In contrast, IFN-induced STAT-1/3 phosphorylation was
      considerably downregulated by SOCS-1/3 overexpression. In mock-transfected cells,
      IFN-alpha induced 2',5'-OAS and myxovirus resistance A (MxA) promoter activity 40
      to 80-fold and 10- to 35-fold, respectively, and this effect was abrogated in
      SOCS-1/3 overexpressing cells. As detected by Northern blot technique, IFN-alpha
      potently induced 2',5'-OAS and MxA mRNA expression in the control clones.
      Overexpression of SOCS-1 completely abolished both 2',5'-OAS and MxA mRNA
      expression, whereas SOCS-3 mainly inhibited 2',5'-OAS mRNA expression. Our
      results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced
      activation of the Jak-STAT pathway and expression of the antiviral proteins 2',5'
      OAS and MxA. These data suggest a potential role of SOCS proteins in IFN
      resistance during antiviral treatment.

PMID- 15240149
TI  - Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy.
AB  - Cardiac hypertrophy is characterized by increased cardiomyocyte size, mRNA levels
      for atrial natriuretic factor (ANF), and protein synthesis. Although activation
      of the phosphoinositide-specific phospholipase C (PLC) leads to the generation of
      diacylglycerol (DAG) and inositol 1,4,5-trisphosphate, the involvement of PLC in
      hypertrophic response remains to be fully understood. The present study was
      therefore undertaken to examine if the inhibition of PLC activity is associated
      with a decrease in ANF expression and protein synthesis in cardiomyocytes, due to
      norepinephrine (NE), a known hypertrophic agent. NE resulted in an increase in
      ANF gene expression and protein synthesis in adult rat cardiomyocytes, these
      effects of NE were attenuated by a PLC inhibitor, U73122. The NE-induced increase
      in ANF gene expression and protein synthesis was also inhibited by an alpha
      adrenoceptor blocker, prazosin. Both U73122 and prazosin depressed the NE-induced
      increase in DAG production in cardiomyocytes. These results indicate that the
      alpha-adrenoceptor mediated PLC activation may be involved in the process of NE
      induced cardiac hypertrophy.

PMID- 15240150
TI  - Phototoxicity and photoinactivation of blebbistatin in UV and visible light.
AB  - Blebbistatin was recently identified as a selective, cell-permeant inhibitor of
      myosin II. Because blebbistatin is likely to be used extensively with
      fluorescence imaging in studies of cytoskeletal dynamics, its compatibility with
      common excitation wavelengths was examined. Illumination of blebbistatin-treated
      bovine aortic endothelial cells at 365 and 450-490 nm, but not 510-560 or 590-650
      nm, caused dose-dependent cell death. Illumination of blebbistatin alone at 365
      and 450-490 nm changed its absorption and emission spectra, but the resultant
      compounds were not toxic. In addition, photoreacted blebbistatin no longer
      disrupted myosin distribution in cells, indicating loss of pharmacological
      activity. Fluorescence microscopy showed that upon illumination, blebbistatin
      became bound to cells and to protein-coated glass, suggesting that toxicity may
      arise from light-induced reaction of blebbistatin with cell proteins.
      Blebbistatin should be used only with careful consideration of these
      photochemical effects.

PMID- 15240151
TI  - Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells:
      involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB.
AB  - Induction of human beta-defensin 2 (HBD-2) by interleukin-1beta (IL-1beta) in
      epithelial cells has been reported. However, the mechanism by which IL-1beta up
      regulates HBD-2 remains poorly understood. In this study, we investigated the
      effect of IL-1beta on induction of HBD-2 in A549 cells. IL-1beta markedly
      increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD
      2 mRNA expression in response to IL-1beta was attenuated by pretreatment of
      GF109203X, Go6976, and staurosporine [inhibitors of protein kinase C (PKC)],
      SB203580 [an inhibitor of p38 mitogen-activated protein kinase (MAPK)], SP600125
      [an inhibitor of c-Jun N-terminal kinase (JNK)], and LY294002 [an inhibitor of
      phosphatidylinositol-3-kinase (PI3K)], but not PD98059 [an inhibitor of
      extracellular signal-regulated kinase (ERK)], suggesting involvement of PKC, p38
      MAPK, JNK, and PI3K in this response. Interestingly, IL-1beta induced nuclear
      factor-kappaB (NF-kappaB) activation in A549 cells, which was shown by increased
      nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha.
      Importantly, IL-1beta-induced HBD-2 mRNA expression was inhibited by blockage of
      NF-kappaB activation using NF-kappaB inhibitors, including pyrrolidine
      dithiocarbamate and MG132. Specifically, IL-1beta-induced nuclear translocation
      of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580,
      and SP600125, suggesting PI3K-dependent nuclear translocation of NF-kappaB in
      response to IL-1beta. Together, these results suggest that IL-1beta induces HBD-2
      mRNA expression in A549 cells, and the induction seems to be at least in part
      mediated through activation of NF-kappaB transcription factor as well as
      activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK.

PMID- 15240152
TI  - RICH-1 has a BIN/Amphiphysin/Rvsp domain responsible for binding to membrane
      lipids and tubulation of liposomes.
AB  - RhoGAP interacting with CIP4 homologs-1 (RICH-1) was previously found in a yeast
      two-hybrid screen for proteins interacting with the SH3 domain of the Cdc42
      interacting protein 4 (CIP4). RICH-1 was shown to be a RhoGAP for Cdc42 and Rac.
      In this study, we show that the BIN/Amphiphysin/Rvsp (BAR) domain in RICH-1
      confers binding to membrane lipids, and has the potential to deform spherical
      liposomes into tubes. In accordance with previous findings for the BAR domains in
      endophilin and amphiphysin, RICH-1-induced tubes appeared striated. We propose
      that these striated structures are formed by oligomerization of RICH-1 through a
      putative coiled-coil region within the BAR domain. In support of this notion, we
      show that RICH-1 forms oligomers in the presence of the chemical cross-linker
      BS3. These results point to an involvement of RICH-1 in membrane deformation
      events.

PMID- 15240153
TI  - Single muscle fiber gene expression in human skeletal muscle: validation of
      internal control with exercise.
AB  - Reverse transcription and real-time PCR have become the method of choice for the
      detection of low-abundance mRNA transcripts obtained from small human muscle
      biopsy samples. GAPDH, beta-actin, beta-2M, and 18S rRNA are widely employed as
      endogenous control genes, with the assumption that their expression is
      unregulated and constant for given experimental conditions. The aim of this study
      was to determine if mRNA transcripts could be performed on isolated human single
      muscle fibers and to determine reliable housekeeping genes (HKGs) using
      quantitative gene expression protocols at rest and in response to an acute
      exercise bout. Muscle biopsies were obtained from the gastrocnemius of three
      adult males before, immediately after, and 4 h following 30 min of treadmill
      running at 70% of VO2max. A total of 40 single fibers (MHC I and IIa) were
      examined for GAPDH, beta-actin, beta-2M, and 18S rRNA using quantitative RT-PCR
      and SYBR Green detection. All analyzed single fiber segments showed ribosomal RNA
      (28S/18S). No degradation or additional bands below ribosomal were detected (rRNA
      ratio 1.5-1.8). Also, no high or low-molecular weight genomic DNA contamination
      was observed. For each housekeeping gene the duplicate average SD was +/-0.13
      with a CV of 0.58%. Stable expression of GAPDH was observed at all time points
      for each fiber type (MHC I and IIa). Inconsistent expression of beta-actin, beta
      2M, and 18S rRNA was observed during the post-exercise time points for each fiber
      type. These data indicate that successful extraction of high quality RNA from
      human single muscle fibers along with quantification of mRNA of selected genes
      can be performed. Furthermore, exercise does influence the expression of certain
      HKGs with GAPDH being the most stable.

PMID- 15240154
TI  - Antiphospholipid antibodies: immunological aspects.

PMID- 15240155
TI  - Detection and characterization of B cell epitopes on beta2-glycoprotein I.
AB  - Autoantibodies in antiphospholipid syndrome react predominantly with the plasma
      protein beta2-glycoprotein I (beta2GPI). Work by a large number of investigators
      has led to considerable progress in detecting and understanding beta2GPI
      reactivity with autoantibodies. Characterization of B cell epitopes on beta2GPI
      has benefited from an appreciation of its interactions with anionic phospholipids
      and a variety of microplate surfaces. In particular, autoantibodies to beta2GPI
      are of sufficiently low affinity to require high concentrations of antigen for
      detectable reactivity. Moreover, some microplate surfaces do not support the
      proper orientation of beta2GPI to allow display of epitopes in a manner
      accessible to autoantibodies. These concepts have helped to explain previous
      notions that exposure of cryptic beta2GPI epitopes may require interactions with
      anionic surfaces. Finally, we review evidence identifying a dominant B cell
      epitope that is partially defined by residues Gly40 and Arg43 on the amino
      terminal domain of beta2GPI.

PMID- 15240156
TI  - Beta-2 glycoprotein I and its role in antiphospholipid syndrome-lessons from
      knockout mice.
AB  - The antiphospholipid syndrome is characterized by the presence in serum of
      autoantibodies against beta2GPI. Although the role of beta2GPI in the
      pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its
      exact physiological functions still remain undisclosed. Several interactions of
      beta2GPI with components of the coagulation cascade have been proposed, resulting
      in both procoagulant and anticoagulant effects. Additionally, beta2GPI has been
      implicated in the mechanism of recurrent fetal loss entailed in APS. Recently,
      using a homologous recombination approach, reproduction of mice homozygous for
      deletion of the beta2GPI gene has been feasible. beta2GPI knockout mice offer a
      valuable tool for revealing the physiological role of the protein. These mice
      show decreased in vitro ability for thrombin generation. Furthermore, although
      mice lacking beta2GPI are fertile, the success of early pregnancy is moderately
      compromised and functional beta2GPI is believed necessary for optimal
      implantation and placental morphogenesis.

PMID- 15240157
TI  - Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome.
AB  - The preliminary classification criteria for definite antiphospholipid syndrome
      (APS) include the presence of anticardiolipin antibodies (aCL) and/or lupus
      anticoagulant (LA) as laboratory criteria. However, antiphospholipid antibodies
      (aPL) are a heterogeneous group of antibodies comprising also antibodies against
      phospholipid-binding proteins or their complexes with phospholipids. Prothrombin
      is one of the antigen recognized by aPL. In the last decade, there has been
      increasing interest in antibodies against prothrombin alone and those against
      phosphatidylserine-prothrombin complex. The latter, phosphatidylserine-dependent
      antiprothrombin antibodies (aPT), have been closely associated with APS and LA.
      In this paper, we review the properties of antiprothrombin antibodies.

PMID- 15240158
TI  - The effect of phospholipids on the formation of immune complexes between
      autoantibodies and beta2-glycoprotein I or prothrombin.
AB  - In the last decennium, it became clear that antiphospholipid antibodies found in
      patients with antiphospholipid syndrome (APS) are in fact antibodies against
      lipid-bound plasma proteins. The most frequently occurring antigens are beta2
      glycoprotein I and prothrombin, although several other lipid-bound plasma
      proteins have been reported as antigen for antiphospholipid antibodies. Both
      proteins bind to anionic phospholipids, mainly phosphatidylserine, which becomes
      exposed at the surface of activated platelets, apoptotic cells, or cell-derived
      microparticles. The binding of beta2-glycoprotein I and prothrombin to these cell
      surfaces or to artificial lipid vesicles with comparable amounts of anionic
      phospholipids is rather weak. Antiphospholipid antibodies from patients are
      predominantly of low affinity regarding their interaction with beta2-glycoprotein
      I or prothrombin in solution. In the presence of a suitable phospholipid surface,
      however, this interaction is strongly enhanced. There is now strong evidence that
      formation of bivalent, trimolecular immune complexes at the lipid membrane
      essentially contributes to the binding of these intrinsically low affinity
      patient antibodies. Depending on the affinity, the epitope specificity, and the
      polyclonality of a particular IgG preparation, multimeric structures of lipid
      bound immune complexes may form a lattice with multiple interactions on the lipid
      (cell) surface. It is hypothesized that the functional activity, that is, the
      ability of antibodies to interfere with lipid-dependent reactions, not only
      depends on their affinity for the antigen, but also on their ability to form
      multiple interconnected bivalent trimolecular complexes at the lipid (or cell)
      surface. It is further proposed that the rate of desorption of immune complexes
      may present a better indicator for the functional properties of the antibodies
      than the amount of adsorbed immune complexes.

PMID- 15240159
TI  - beta2-glycoprotein I, the playmaker of the antiphospholipid syndrome.
AB  - From its discovery in the early 60s till the beginning of the 90s, there was not
      much interest in plasma protein beta2-glycoprotein I (beta2-GPI). The finding
      that beta2-GPI acts as an essential cofactor for the detection of
      antiphospholipid antibodies (aPL) tremendously increased the interest in beta2
      GPI [Lancet 335 (1990) 1544; Lancet 336 (1990) 177; Proc. Natl. Acad. Sci. U. S.
      A. 87 (1990) 4120]. It is now generally accepted that autoantibodies directed
      towards beta2-GPI are not only a serological marker but that they are involved in
      the pathology of the antiphospholipid syndrome (APS). In this review, we will
      first discuss the biochemistry of the protein beta2-GPI and the influence that
      the antibodies have on the function of beta2-GPI. Next, we will discuss the
      problems that are faced when assays to detect the presence of the autoantibodies
      are performed, emphasizing the urgent need for standardization of the anti-beta2
      GPI-ELISA. Finally, we will discuss our latest insights into beta2-GPI and its
      role in the pathology of APS. Thereby, we will focus on the role of dimerized
      beta2-GPI on platelet and endothelial cell function.

PMID- 15240160
TI  - Endothelial cell activation by antiphospholipid antibodies.
AB  - Antiphospholipid antibodies are mainly directed against beta 2 glycoprotein I, a
      phospholipid-binding protein expressed on endothelial cell membranes of different
      anatomical localizations and recognized by the specific autoantibodies. Antibody
      binding induces an endothelial activation both in in vitro and in vivo
      experimental models that might contribute to the prothrombotic state. Endothelial
      beta 2 glycoprotein I adhesion is mediated by the electrostatic interaction
      between its cationic phospholipid binding site and anionic structures on the cell
      membrane; however, binding to annexin II--the endothelial cell receptor for
      tissue plasminogen activator--plays also a role. Anti-beta-2 glycoprotein I
      antibodies up-regulate mRNA expression of pro-inflammatory mediators through NF
      kappaB translocation and the signaling cascade triggered by Toll-like receptors.
      Because of the molecular mimicry between beta 2 glycoprotein I and
      viral/bacterial structures-the natural ligands for Toll-like receptors (TLR)
      antibodies might cross-link the molecule associated to the receptors eventually
      triggering their signaling.

PMID- 15240161
TI  - Apoptosis, subcellular particles, and autoimmunity.
AB  - Firm evidence links the process of apoptosis to the induction of autoimmune
      disease. However, questions remain regarding the precise interactions of dying
      cells with the immune system. Genetic analyses indicate that deficiencies in
      serum proteins or receptors that mediate clearance of apoptotic cells increase
      the risk of autoimmunity. Moreover, administration of apoptotic cells to naive
      animals elicits transient autoimmune responses. Because known autoantigens are
      covalently modified and redistributed to cell surface blebs during the execution
      stage of apoptosis, increasing attention is being directed at this stage of
      programmed cell death, and researchers have identified a variety of autoantigens
      that are sequestered within blebs. However, blebs are merely a transition stage
      toward the complete cellular fragmentation, as blebs quickly convert into
      apoptotic bodies, subcellular particles (SCPs) of heterogeneous size, surface
      composition, and cargo. Because certain types of subcellular particles represent
      packets of highly enriched autoantigens, we propose that they are relevant to our
      understanding of autoimmunity.

PMID- 15240162
TI  - Antiphospholipid antibodies and atherosclerosis.
AB  - Antiphospholipid antibodies (APA) are present in a variety of autoimmune
      disorders, including systemic lupus erythematosus (SLE) and the antiphospholipid
      syndrome (APS). Increasing evidence suggests that a subset of APA can also be
      detected in patients with atherosclerosis. In this review, we discuss the
      specificities of the autoantibodies that are present during both APS and
      atherosclerosis. A critical and unresolved question is whether these APA are
      specific for epitopes that result from lipid oxidation. Despite the fact that APA
      are present in patients with systemic autoimmunity and that they may participate
      in the pathogenesis of APS, recent studies have paradoxically proposed a
      beneficial role for some APA in atherosclerosis. We review the evidence that some
      APA specificities may be protective against plaque formation, and we discuss the
      putative mechanisms by which some APA could be useful in the prevention of
      atherosclerosis.

PMID- 15240163
TI  - Beta-2-glycoprotein-I, infections, antiphospholipid syndrome and therapeutic
      considerations.
AB  - Evidence supports the association between infectious agents, antiphospholipid
      syndrome (APS), and the presence of antiphospholipid antibodies and anti-beta2
      glycoprotein-I (beta2GPI) antibodies. Several mechanisms have been proposed to
      explain the role of bacteria/viruses in induction of an autoimmune condition,
      such as molecular mimicry between structures of a pathogen and self antigen and
      bystander activation or bacterial/viral superantigens. Protein databases reveal
      high homologies between the beta2GPI-related synthetic peptides and infectious
      agents. Studies employing experimental APS models proved molecular mimicry
      between beta2GPI-related synthetic peptides, which serve as target epitopes for
      anti-beta2GPI Abs, and structures within bacteria, viruses (e.g., CMV), and
      tetanus toxoid. Any explanation of how microbial infections might induce APS must
      take into account the genetic predisposition. In this paper, we discuss the
      association of antiphospholipid antibodies, infectious states, and molecular
      mimicry as a proposed mechanism for development of APS.

PMID- 15240164
TI  - Interaction of phenanthrene and its primary metabolite (1-hydroxy-2-naphthoic
      acid) with estuarine sediments and humic fractions.
AB  - Experiments were conducted to compare the sorption and desorption of phenanthrene
      and its primary degradation product, 1-hydroxy-2-naphthoic acid (HNA), in
      estuarine sediment, humic acid (HA) and humin. Ionic composition, ionic strength
      (0.4 M) and pH (7.6) were employed to mimic native estuarine pore water at the
      sediment-water interface. Sorption to whole sediment and organic matter (OM)
      fractions was significantly lower for HNA than for phenanthrene. Whereas HNA did
      not sorb to HA, uptake to sediment and humin was observed, suggesting that HNA
      does not bind directly to OM. Phenanthrene uptake was characterized by hysteretic
      behavior and exhibited slow desorption. In contrast, HNA initially was more
      readily desorbed from sediment and humic fractions, but a significant fraction
      was not recovered in repeated desorption runs. The lower sorption of HNA reflects
      its greater polarity and water solubility, but the consistent retention of a non
      desorbing fraction suggests strong binding and/or chemical transformation
      reactions may be important. It was postulated that abiotic transformation of HNA
      may occur in estuarine sediments, in part due to the presence of redox active
      minerals (Fe(III) and Mn(IV) oxides). The presence of Fe and Mn solids in the
      estuarine sediment was verified by sequential extraction and studies were then
      conducted to investigate the transformation of HNA in the presence of synthetic
      goethite (alpha-FeOOH) and birnessite (delta-MnO2) as model solids. Reaction with
      birnessite led to transformation of all HNA in solution within 24 h and resulted
      in the formation of partial oxidation products (POPs). Following reaction with
      goethite, HNA was present in solution and POPs were observed in the weakly bound
      fraction. This study indicates that degradation products of polycyclic aromatic
      hydrocarbons (PAHs) may have distinctly different sorption affinities and
      reactivities toward environmental surfaces than their parent compounds.

PMID- 15240166
TI  - Interaction of reactive fronts during transport in a homogeneous porous medium
      with initial small non-uniformity.
AB  - A reactive fluid circulating within a porous medium can dissolve minerals with
      which it is out of equilibrium and modify the porosity and permeability. The
      positive feedback between fluid transport and mineral dissolution causes complex
      reaction front morphologies such as fingers or wormholes. This study presents a
      numerical model to investigate reaction front instability, temporal aquifer
      porosity, and species concentration evolution during reactive transport in a
      homogeneous porous medium with two small, initially local non-uniformities.
      Simulation results indicate that a stable planar front develops for a small
      upstream pressure gradient while the growth of two non-uniformities becomes
      unstable for a large upstream pressure gradient. Moreover, the unstable reaction
      front may be either double- or single-finger in shape. Reaction front shape
      selection depends on the spacing of the two local non-uniformities and the
      upstream pressure gradients. A behavior diagram is constructed to identify a
      planar, single- or double-front morphology. The critical non-uniformities spacing
      at which a reaction front begins to merge into a single-finger decreases with
      increasing upstream pressure gradient.

PMID- 15240165
TI  - Anomalous transport of colloids and solutes in a shear zone.
AB  - Transport experiments with colloids and radionuclides in a shear zone were
      conducted during the Colloid and Radionuclide Retardation experiment (CRR) at
      Nagra's Grimsel Test Site. Breakthrough curves of bentonite colloids and uranine,
      a non-sorbing solute, were measured in an asymmetric dipole flow field. The
      colloid breakthrough is earlier than that of uranine. Both breakthrough curves
      show anomalously long late time tails and the slope of the late time tails for
      the colloids is slightly higher. Anomalous late time tails are commonly
      associated with matrix diffusion processes; the diffusive interaction of solutes
      transported in open channels with the adjacent porous rock matrix or zones of
      stagnant water. The breakthrough curves for different colloid size classes are
      very similar and show no signs of fractionation due to their (size-dependent)
      diffusivity. It is proposed that tailing of the colloids is mainly caused by the
      structure of the flow field and that for the colloid transport, matrix diffusion
      is of minor importance. This has consequences for the interpretation of the
      uranine breakthrough. Comparisons of experimental results with numerical studies
      and with the evaluation of the colloid breakthrough with continuous time random
      theory imply that the tailing in the conservative solute breakthrough in this
      shear zone is not only caused by matrix diffusion. Part of the tailing can be
      attributed to advective transport in fracture networks and advection in low
      velocity regions. Models based on the advection-dispersion equation and matrix
      diffusion do not properly describe the temporal and spatial evolution of colloid
      and solute transport in such systems with a consistent set of parameters.

PMID- 15240167
TI  - Influence of residual surfactants on DNAPL characterization using partitioning
      tracers.
AB  - The partitioning tracer technique is among the DNAPL source-zone characterization
      methods being evaluated, while surfactant in-situ flushing is receiving attention
      as an innovative technology for enhanced source-zone cleanup. Here, we examine in
      batch and column experiments the magnitude of artifacts introduced in estimating
      DNAPL content when residual surfactants are present. The batch equilibrium tests,
      using residual surfactants ranging from 0.05 to 0.5 wt.%, showed that as the
      surfactant concentrations increased, the tracer partition coefficients decreased
      linearly for sodium hexadecyl diphenyl oxide disulfonate (DowFax 8390), increased
      linearly for polyoxyethylene (10) oleyl ether (Brij 97), and decreased slightly
      or exhibited no observable trend for sodium dihexyl sulfosuccinate (AMA 80).
      Results from column tests using clean sand with residual DowFax 8390 and
      Tetrachloroethylene (PCE) were consistent with those of batch tests. In the
      presence of DowFax 8390 (less than 0.5 wt.%), the PCE saturations were
      underestimated by up to 20%. Adsorbed surfactants on a loamy sand with positively
      charged oxides showed false indications of PCE saturation based on partitioning
      tracers in the absence of PCE. Using no surfactant (background soil) gave a false
      PCE saturation of 0.0004, while soil contacted by AMA 80, Brij 97, and DowFax
      8390 gave false PCE saturations of 0.0024, 0.043, and 0.23, respectively.

PMID- 15240168
TI  - Analytical model of solute transport by unsteady unsaturated gravitational
      infiltration.
AB  - Penetration of reactive solute into a soil during a cycle of water infiltration
      and redistribution is investigated by deriving analytical closed form solutions
      for fluid flux, moisture content and contaminant concentration. The solution is
      developed for gravitational flow and advective transport and is applied to two
      scenarios of solute applications encountered in the applications: a finite pulse
      of solute dissolved in irrigation water and an instantaneous pulse broadcasted
      onto the soil surface. Through comparison to simulations of Richards' flow,
      capillary suction is shown to have contrasting effects on the upper and lower
      boundaries of the fluid pulse, speeding penetration of the wetting front and
      reducing the rate of drying. This leads to agreement between the analytical and
      numerical solutions for typical field and experimental conditions. The analytical
      solution is further incorporated into a stochastic column model of flow and
      transport to compute mean solute concentration in a heterogeneous field. An
      unusual phenomenon of plume contraction is observed at long times of solute
      propagation during the drying stage. The mean concentration profiles match those
      of the Monte-Carlo simulations for capillary length scales typical of sandy
      soils.

PMID- 15240169
TI  - Migration of saline solutions in variably saturated porous media.
AB  - Migration of concentrated NaNO3 solutions in homogeneous packs of pre-wetted
      silica sands was investigated using a light transmission system. Solutions of 5
      molal NaNO3 were found to migrate downward 24-62% faster than pure water, in an
      unstable, fingered manner. This behavior was attributed primarily to a surface
      tension induced, non-zero apparent contact angle between the imbibing and the
      resident fluids. For saline solutions of similar surface tension to that of pure
      water (achieved by the addition of 2% methanol), the migration rates and plume
      shapes were comparable to that of water, demonstrating that density was not the
      primary source of the observed differences in migration patterns. At depths where
      resident saturation increased above residual, the migration process appeared to
      occur via film flow with slight changes in saturation (<4%), rather than in a
      series of abrupt jumps, as observed at shallower depths. A method for contact
      angle scaling was used to illustrate the effects of non-zero contact angles on
      capillary pressure-saturation curves.

PMID- 15240170
TI  - Migration of contaminants through the unsaturated zone overlying the Hesbaye
      chalky aquifer in Belgium: a field investigation.
AB  - This paper presents the results of a detailed field investigation that was
      performed for studying groundwater recharge processes and solute downward
      migration mechanisms prevailing in the unsaturated zone overlying a chalk aquifer
      in Belgium. Various laboratory measurements were performed on core samples
      collected during the drilling of boreholes in the experimental site. In the
      field, experiments consisted of well logging, infiltration tests in the
      unsaturated zone, pumping tests in the saturated zone and tracer tests in both
      the saturated and unsaturated zones. Results show that gravitational flows govern
      groundwater recharge and solute migration mechanisms in the unsaturated zone. In
      the variably saturated chalk, the migration and retardation of solutes is
      strongly influenced by recharge conditions. Under intense injection conditions,
      solutes migrate at high speed along the partially saturated fissures, downward to
      the saturated zone. At the same time, they are temporarily retarded in the almost
      immobile water located in the chalk matrix. Under normal recharge conditions,
      fissures are inactive and solutes migrate slowly through the chalk matrix.
      Results also show that concentration dynamics in the saturated zone are related
      to fluctuations of groundwater levels in the aquifer. A conceptual model is
      proposed to explain the hydrodispersive behaviour of the variably saturated
      chalk. Finally, the vulnerability of the chalk to contamination issues occurring
      at the land surface is discussed.

PMID- 15240171
TI  - Nitrate in groundwater: an isotopic multi-tracer approach.
AB  - In spite of increasing efforts to reduce nitrogen inputs into groundwater from
      intensive agriculture, nitrate (NO3) remains one of the major pollutants of
      drinking-water resources worldwide. Determining the source(s) of NO3
      contamination in groundwater is an important first step for improving groundwater
      quality by emission control, and it is with this aim that we investigated the
      viability of an isotopic multi-tracer approach (delta15N, delta11B, 87Sr/86Sr),
      in addition to conventional hydrogeologic analysis, in two small catchments of
      the Arguenon watershed (Brittany, France). The main anthropogenic sources
      (fertilizer, sewage effluent, and hog, cattle and poultry manure) were first
      characterized by their specific B, N and Sr isotope signatures, and compared to
      those observed in the ground- and surface waters. Chemical and isotopic evidence
      shows that both denitrification and mixing within the watershed have the effect
      of buffering NO3 contamination in the groundwater. Coupled delta11B, delta15N and
      87Sr/86Sr results indicate that a large part of the NO3 contamination in the
      Arguenon watershed originates from the spreading of animal manure, with hog
      manure being a major contributor. Point sources, such as sewage effluents,
      contribute to the NO3 budget of the two watersheds.

PMID- 15240172
TI  - Spatial distribution of pollution in an urban stormwater infiltration basin.
AB  - Infiltration basins are frequently used for stormwater drainage. Because
      stormwater is polluted in highly toxic compounds, assessment of pollution
      retention by infiltration basins is necessary. Indeed, if basins are not
      effective in trapping pollution, deep soil and groundwater may be contaminated.
      This study's objective is to investigate soil pollution in infiltration basins:
      spatial distribution of soil pollution, optimisation of the number of soil
      samples and a contamination indicator are presented. It is part of a global
      project on long-term impact of stormwater infiltration on groundwater. Soil
      sampling was done on a basin in suburban Lyon (France). Samples were collected at
      different depths and analysed for nutrients, heavy metals, hydrocarbons and grain
      size. Pollutant concentrations decrease rapidly with depth while pH,
      mineralisation and grain size increase. Sustainable metal concentrations are
      reached at a 30-cm depth, even after 14 years of operation; hydrocarbon pollution
      is deeper. Principal component analysis shows how pollutants affect each level.
      The topsoil is different from other levels. Three specifically located points are
      enough to estimate the mass of pollution trapped by the basin with a 26% error.
      The proposed contamination indicator is calculated using either average level
      concentrations or maximum level concentrations. In both cases, the topsoil layer
      appears polluted but evaluation of lower levels is dependent on the choice of
      input concentrations.

PMID- 15240173
TI  - Remediation of NAPL below the water table by steam-induced heat conduction.
AB  - Previous experimental studies have shown that NAPL will be removed when it is
      contacted by steam. However, in full-scale operations, steam may not contact the
      NAPL directly and this is the situation addressed in this study. A two
      dimensional intermediate scale sand box experiment was performed where an organic
      contaminant was emplaced below the water table at the interface between a coarse
      and a fine sand layer. Steam was injected above the water table and after an
      initial heating period the contaminant was recovered at the outlet. The
      experiment was successfully modeled using the numerical code T2VOC and the
      dominant removal mechanism was identified to be heat conduction induced boiling
      of the separate phase contaminant. Subsequent numerical modeling showed that this
      mechanism was insensitive to the porous medium properties and that it could be
      evaluated by considering only one-dimensional heat conduction.

PMID- 15240174
TI  - Kinetics of soil ozonation: an experimental and numerical investigation.
AB  - This study investigates the use of ozone for soil remediation. Batch experiments,
      in which ozone-containing gas was continuously recycled through a soil bed, were
      conducted to quantify the rate of ozone self-decomposition and the rates of ozone
      interaction with soil organic and inorganic matter. Column experiments were
      conducted to measure ozone breakthrough from a soil column. Parameters such as
      ozone flow rate, soil mass, and ozonation time were varied in these experiments.
      After ozone concentration had reached steady state, the total organic carbon
      concentration was measured for all soil samples. The ozonation efficiency,
      represented by the ratio of soil organic matter consumed to the total ozone
      input, was quantified for each experiment. Numerical simulations were conducted
      to simulate experimentally obtained column breakthrough curves. Experimentally
      obtained kinetic rate constants were used in these simulations, and the results
      were in good agreement with experimental data. In contrast to previous studies in
      which soil inorganic matter was completely ignored, our experiments indicate that
      soil inorganic matter may also promote depletion of ozone, thus reducing the
      overall ozonation efficiency. Three-dimensional numerical simulations were
      conducted to predict the efficacy of ozonation for soil remediation in the field.
      These simulations indicate that such ozonation can be very effective, provided
      that effective circulation of ozone is achieved through appropriately placed
      wells.

PMID- 15240175
TI  - Simple screening models of NAPL dissolution in the subsurface.
AB  - Three simple screening models of nonaqueous phase liquid (NAPL) dissolution in
      the subsurface are proposed based on the NAPL mass conservation and the
      assumption of proportionality between the residual NAPL source zone concentration
      and the remaining residual NAPL mass. The purpose of the proposed models is to
      predict the solute concentration in the zone of the residual NAPL as a result of
      dissolution. The predicted source zone concentration decrease is used to simulate
      and account for the decrease of dissolution rate with time. The proposed simple
      NAPL dissolution models enable the pseudo-equilibrium formulation to be used and
      therefore the numerical simulations for field application problems can be
      simplified compared to the non-equilibrium counterpart. With proper choice of
      empirical parameters, the proposed simple screening models can work as well as
      more complex dissolution rate correlation models, such as that of Imhoff et al.
      [Water Resour. Res. 30 (1994) 307-320]. It is found that the proposed models are
      very good for quantifying non-equilibrium dissolution, which is characterized by
      tailing of breakthrough curves. The models are especially useful for situations
      of small residual NAPL saturation, which are typical for many field applications.

PMID- 15240176
TI  - Explicit and implicit coupling during solute transport through clay membrane
      barriers.
AB  - Simulations of salt (KCl) flux through a 1-m-thick clay membrane barrier (CMB)
      based on coupled solute transport theory are compared to simulated fluxes based
      on traditional advective-dispersive transport theory. The simulations are based
      on measured values for the effective salt-diffusion coefficient (Ds*) and chemico
      osmotic efficiency coefficient (omega) for a bentonite-based barrier material
      subjected to KCl solutions. The results indicate that the exit salt flux is
      reduced due to both explicit coupling (hyperfiltration and chemico-osmotic
      counter-advection) and an implicit coupling effect resulting from the decrease in
      Ds* due to a decrease in the apparent tortuosity factor, tau a, with an increase
      in omega. Implicit coupling is shown to be more significant than explicit
      coupling for reducing and retarding salt flux through a CMB under diffusion
      dominated conditions. Failure to account for the implicit coupling effect may
      result in unrealistic results, such as the existence of salt flux through a
      perfect (ideal) clay membrane (i.e., omega=1).

PMID- 15240177
TI  - Characterization of the non-competitive antagonist binding site of the NMDA
      receptor in dark Agouti rats.
AB  - The ability of non-competitive NMDA antagonists and other selected compounds to
      inhibit [3H]MK-801 binding to the NMDA receptor in brain membranes was evaluated
      in female, dark Agouti rats. In homologous competition binding studies the
      average apparent affinity (KD) of [3H]MK-801 for its binding site was 5.5 nM and
      the binding site density (Bmax) was 1.83 pmol/mg protein. Inhibition of [3H]MK
      801 binding by non-competitive NMDA antagonists was best described with a one
      site competition model and the average Hill coefficients were -1. A series of
      eight non-competitive NMDA antagonists inhibited [3H]MK-801 binding with the
      following rank order of affinity (K(i), nM): MK-801 (5.5) > dexoxadrol (21.5) >
      or = TCP (24.2) > phencyclidine (100.8) > (+)-SKF 10,047 (357.7) > dextrorphan
      (405.2) > ketamine (922.2) > dextromethorphan (2913). These inhibition binding
      constants determined in dark Agouti rat brain membranes were significantly
      correlated (P = 0.0002; r2 = 0.95) with previously reported values determined in
      Sprague-Dawley rats [Wong et al., 1988, J. Neurochem. 50, 274-281]. Despite
      significant differences in metabolic capability between these strains, the
      central nervous system NMDA receptor ion channel shares similar characteristics.

PMID- 15240178
TI  - Methylguanidine reduces the development of non septic shock induced by zymosan in
      mice.
AB  - In the present study we evaluate the effect of methylguanidine (MG), a product of
      protein catabolism, in a model of acute inflammation (zymosan induced
      inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role.
      Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits
      the inflammatory response reducing significantly (P < 0.05) peritoneal exudates
      formation, mononuclear cell infiltration and histological injury in mice.
      Furthermore, our data suggests that there is a significant (P < 0.05) reduction
      in kidney, liver and pancreas injury as demonstrated by the reduction in amylase,
      lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is
      also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme
      poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the
      inflamed intestinal and lung tissues. The histological examination revealed a
      significant reduction in zymosan-induced intestinal and lung damage in MG-treated
      mice. Taken together, the present results demonstrate that MG exerts potent anti
      inflammatory effects on zymosan-induced shock.

PMID- 15240179
TI  - Leptin deficiency enhances myocardial necrosis and lethality in a murine model of
      viral myocarditis.
AB  - To investigate the role of leptin in the development of viral myocarditis and
      cardiac necrosis, we used a murine model of viral myocarditis. We
      intraperitoneally injected encephalomyocarditis virus (500 plaque-forming
      units/mouse) for wild type C57 BL/6 mice (WT) and leptin-deficient ob/ob mice
      (OB) (n = 20 for each). Ten-day survival rate was 25% in OB, whereas it was 95%
      in WT. Heart weights on day 10 were significantly elevated in OB compared with
      those in WT (107.2 +/- 9.4 vs. 96.6 +/- 7.9 mg, n = 4 for each). Thymus weights
      were significantly diminished in OB compared with those in WT on days 6 and 10.
      Histological score (grade 1 to 4 according to the size of involved area) for
      myocardial necrosis were significantly higher in OB than in WT (1.5 +/- 0.5 vs.
      0.8 +/- 0.5, n = 4 for each). On day 4, viral titer in hearts was significantly
      elevated in OB compared with that in WT (3.3 +/- 0.5 vs. 1.9 +/- 0.2 TCID50/mg, n
      = 3 for each). Comparative expression of TNF-alpha mRNA in hearts from OB were
      significantly increased compared with those in WT on day 7 (n = 3 for each).
      Natural killer cell activities in spleens from OB were significantly lower than
      from WT on day 4 (27 +/- 5 vs. 42 +/- 8%, n = 4 for each). Thus, leptin
      deficiency could enhance severity of myocardial necrosis and mortality due to
      viral myocarditis.

PMID- 15240180
TI  - Effects of androgen manipulation on alpha1-adrenoceptor subtypes in the rat
      seminal vesicle.
AB  - This study analyses possible changes during surgical and chemical castration in
      the expression and pharmacological characteristics of alpha1-adrenoceptor in
      adult rat seminal vesicle. Ribonuclease protection assays indicated that alpha1a-
      was the predominant mRNA, while alpha1b-and alpha1d-adrenoceptor transcripts were
      detected in lower abundance in this tissue. alpha1a-adrenoceptor mRNA expression
      presented a complex dependency on androgens, while alpha1b- and alpha1d
      adrenoceptor transcripts were both upregulated with surgical and chemical
      castration, suggesting a negative modulation by androgens. Testosterone treatment
      reversed the effects caused by surgical castration. Functional studies confirmed
      the involvement of alpha1A- and alpha1B-adrenoceptor in the seminal vesicle
      contractile responses, and suggested that alpha1B-induced contractile response
      was upregulated after castration. Taken together, the results suggest that alpha1
      adrenoceptor expression in seminal vesicle is differentially regulated by the
      androgen status of the rat.

PMID- 15240181
TI  - Convergence of nociceptive information from temporomandibular joint and tooth
      pulp afferents on C1 spinal neurons in the rat.
AB  - The aim of the present study was to test the hypothesis that there is a
      convergence of afferent inputs from the temporomandibular joint (TMJ) on C1
      spinal neurons responding to electrical stimulation of the tooth pulp (TP). In 14
      pentobarbital anesthetized rats, the extracellular single unit activity of 31 C1
      spinal neurons and the amplitude in a digastric muscle electromyogram (n = 31)
      increased proportionally during 1.0-3.5 times the threshold for the jaw-opening
      reflex (JOR). Of 31 C1 spinal neurons responsive to TP afferents, 28
      (approximately 90%) were also excited by electrical stimulation of the
      ipsilateral TMJ capsule. All neurons tested were divided into three categories of
      nociceptive specific, wide dynamic range and non-responsive as to their
      responsiveness to mechanical stimuli (pin prick and touch) of the somatic
      receptive field (skin of the face, neck, jaw and upper forearm) and TMJ capsule.
      Nineteen (68%) of 28 C1 spinal neurons received nociceptive information from C
      fibers of the TMJ capsule. These results suggest that there is a convergence of
      noxious information from the TMJ and TP afferents on the same C1 spinal neurons,
      which importantly contribute to pain perception from the TMJ region.

PMID- 15240182
TI  - Synergistic effect on insulin secretion from INS-1 cells of a sulfonylurea and a
      phosphodiesterase 3 inhibitor.
AB  - The effects on insulin secretion from INS-1 cells of varying concentrations of
      the sulfonylurea glyburide and the PDE3 inhibitor milrinone, separately and in
      combination were measured. Over a range of concentrations the effects of the two
      drugs in combination were more than additive. A response surface model was fit to
      the data and was found to describe the data well. From this model, it was
      apparent that a significant synergistic effect upon insulin secretion existed
      over a wide range of combinations of the two drugs.

PMID- 15240183
TI  - Inhibition of inducible nitric oxide synthase expression by yuccaol C from Yucca
      schidigera roezl.
AB  - Yucca schidigera extract finds wide commercial application in foods, cosmetics
      and pharmaceuticals. In a previous paper we have found as the main constituents
      of yucca bark, yuccaol A, B and C, new and very unusual spiro-derivatives made up
      of a C15 unit and a stilbenic portion closely related to resveratrol. This study
      was performed to examine whether yuccaol A, B or C (0.01-100 microM) could affect
      cytosolic inducible nitric oxide synthase (iNOS) protein expression and nitric
      oxide (NO) generation in vitro in Escherichia coli lipopolysaccharide (LPS)
      activated J774.A1 macrophage cell line. NO production, detected as NO2-,
      increased significantly in LPS treated J774.A1 cells from 0.05 +/- 0.03 microM to
      16.64 +/- 0.58 microM (P < 0.001). Yuccaol C (0.01-100 microM), added to the
      culture medium 1 h before LPS-stimulation, significantly (P < 0.001) and in a
      concentration related manner reduced NO release (P < 0.001) and iNOS protein
      expression (P < 0.05). In contrast, no inhibitory effect either on iNOS protein
      expression or on NO release was observed when yuccaol C was added after LPS
      stimulation. In contrast yuccaol A inhibited significantly (P < 0.001) only NO
      release at the highest concentration tested (100 microM) while yuccaol B did not
      reduce either NO release or iNOS expression. Yuccaol C was demonstrated to reduce
      iNOS protein expression via the transcription factor NF-kappaB. These results
      indicated that the empirical use of Y. schidigera as anti-inflammatory remedy
      could be addressed not only to the resveratrol content but also to the presence
      of yuccaol C.

PMID- 15240184
TI  - Possible anxiolytic effects of taurine in the mouse elevated plus-maze.
AB  - The effects of taurine, an inhibitory amino acid, on the behavior of male mice
      were examined in the elevated plus-maze test of anxiety. Acute taurine treatment
      (60 mg/kg, PO) significantly increased the percentage of time spent in the open
      arms. Moreover, when taurine was administered daily for seven days and the plus
      maze test was conducted 40 minutes after the last administration, a significant
      increase of the percentage of time in the open arms was observed even at dose of
      2.5 mg/kg, however the open arm entries and the total entries were unaffected at
      any dose tested. In order to get a comprehensive profile of drug action, detailed
      behavioral analyses were further exerted. Single administration of 60 mg/kg
      taurine can significantly reduce the total rears. The results suggest that
      taurine have some anxiolytic-like properties, although its effects seem more
      limited and are not consistent with those presented by classic anxiolytics, such
      as diazepam.

PMID- 15240185
TI  - Ajulemic acid: A novel cannabinoid produces analgesia without a "high".
AB  - A long-standing goal in cannabinoid research has been the discovery of potent
      synthetic analogs of the natural substances that might be developed as clinically
      useful drugs. This requires, among other things, that they be free of the
      psychotropic effects that characterize the recreational use of Cannabis. An
      important driving force for this goal is the long history of the use of Cannabis
      as a medicinal agent especially in the treatment of pain and inflammation. While
      few compounds appear to have these properties, ajulemic acid (AJA), also known as
      CT-3 and IP-751, is a potential candidate that could achieve this goal. Its
      chemical structure was derived from that of the major metabolite of Delta9-THC,
      the principal psychotropic constituent of Cannabis. In preclinical studies it
      displayed many of the properties of non-steroidal anti-inflammatory drugs
      (NSAIDs); however, it seems to be free of undesirable side effects. The initial
      short-term trials in healthy human subjects, as well as in patients with chronic
      neuropathic pain, demonstrated a complete absence of psychotropic actions.
      Moreover, it proved to be more effective than placebo in reducing this type of
      pain as measured by the visual analog scale. Unlike the narcotic analgesics,
      signs of dependency were not observed after withdrawal of the drug at the end of
      the one-week treatment period. Data on its mechanism of action are not yet
      complete; however, the activation of PPAR-gamma, and regulation of eicosanoid and
      cytokine production, appear to be important for its potential therapeutic
      effects.

PMID- 15240186
TI  - Prophylactic effects of magnesium and vitamin E in rat spinal cord radiation
      damage: evaluation based on lipid peroxidation levels.
AB  - This study investigated the neuroprotective effects of magnesium sulfate
      prophylaxis and vitamin E prophylaxis in a rat model of spinal cord radiation
      injury. Groups were subjected to different treatment conditions for 5 days prior
      to irradiation, and outcomes were evaluated on the basis of lipid peroxidation
      levels in cord tissue. Four groups of rats were investigated: no
      radiation/treatment (n = 4), intraperitoneal (i.p.) saline 1 ml/day (n = 6), i.p.
      vitamin E 100 mg/kg/day (n = 6), and i.p. magnesium sulfate 600 mg/kg/day (n =
      6). The thoracic cord of each non-control rat was exposed to 20 Gy radiation in a
      LINAC system using 6 MV x-rays, and malondialdehyde (MDA) levels (reflecting
      lipid peroxidation level) were determined 24 hours post-irradiation. The MDA
      levels in thoracic cord segments from the control rats were used to determine
      baseline lipid peroxidation. The mean levels in the control, saline-only, vitamin
      E, and magnesium sulfate groups were 12.12 +/- 0.63, 27.0 +/- 2.81, 17.71 +/-
      0.44, and 14.40 +/- 0.47 nmol/mg tissue, respectively. The MDA levels in the
      saline-only group were significantly higher than baseline, and the levels in the
      vitamin E group were significantly lower than those in the saline group (P < 0.05
      for both). The levels in the magnesium sulfate group were dramatically lower than
      those in the saline group (P < 0.001). The results indicate that i.p. magnesium
      sulfate has a marked neuroprotective effect against radiation-induced oxidative
      stress in the rat spinal cord.

PMID- 15240187
TI  - Interferon-beta therapy for MS: the dilemma of having choices.

PMID- 15240188
TI  - A plea for "omics" research in complex diseases such as multiple sclerosis--a
      change of mind is needed.

PMID- 15240189
TI  - Increased ability of peripheral blood lymphocytes to degrade laminin in multiple
      sclerosis.
AB  - T lymphocytes and macrophages probably play a role in the pathogenesis of
      multiple sclerosis (MS), and migration of these cells into the central nervous
      system is facilitated by disruption of the capillary basement membrane. Laminin
      is a major extracellular matrix of the basement membrane. To investigate whether
      ability of lymphocytes to degrade laminin correlates with disease activity in MS,
      we conducted a prospective study in consecutive 24 MS patients. A novel
      quantitative assay was developed to estimate the ability of peripheral blood
      mononuclear cells (PBMCs) to degrade laminin. The assay was performed every four
      weeks over a period of 12 months. During the study period, a total of 41 relapses
      were observed. The ability to degrade laminin was significantly higher in MS
      patients, even during clinical remission, than in normal and neurological
      controls, and was transiently increased further within 4 weeks before relapse
      (p=0.076). In MS, the ability of peripheral blood lymphocytes to degrade laminin
      increases, and may correlate with disease activity.

PMID- 15240190
TI  - High-dose, frequently administered interferon beta therapy for relapsing
      remitting multiple sclerosis must be maintained over the long term: the
      interferon beta dose-reduction study.
AB  - Long-term trials have demonstrated the continued efficacy of interferon (IFN)
      beta treatment in patients with relapsing-remitting (RR) multiple sclerosis (MS)
      during prolonged administration. The objective of the work was to evaluate the
      effects of reducing IFN beta administration frequency and total weekly dose in
      patients with RR MS who have achieved clinical and MRI disease activity
      stabilization during long-term IFN beta-1b treatment. Prospective 1-year follow
      up of 27 RR MS patients on long-term 250 microg every other day (standard dose)
      IFN beta-1b treatment were randomized either to gradually reduce dose to 30
      microg once-a-week IFN beta-1a (13 patients), or to continue on IFN beta-1b
      standard dose (14 patients). We found significant differences in the two group of
      patients. In the group of patients continuously treated with IFN beta-1b standard
      dose, 79% remained relapse free compared to 23% in the group receiving once
      weekly IFN beta-1a (p=0.006). The number of patients without new PD/T2 lesions
      was higher in the group of patients continuously treated with IFN beta-1b
      standard dose (77%) compared to the once-weekly IFN beta-1a group (23%) (p=0.04).
      IFN beta is a long-term treatment for MS. The reduction of IFN beta-1b
      administration frequency and dose is not advisable even in patients free from
      clinical and MRI disease activity for many years.

PMID- 15240191
TI  - Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in
      women with multiple sclerosis.
AB  - Pregnancy in multiple sclerosis (MS) patients is associated with a lower risk of
      progression and lower rate of exacerbation. These beneficial effects are reversed
      postpartum. Considering that the pathogenesis of MS appears to involve cell
      mediated immune reactivity, and that pregnancy is accompanied by a depressed cell
      mediated immunity, it has been proposed that the lower relapse rate and risk of
      progression of MS during pregnancy may be due to a pregnancy-associated down
      regulation of cell-mediated immunity. In addition, pregnancy results in a shift
      towards a T helper (Th) 2 cytokine profile, which is presumably protective for
      MS. This study was aimed at investigating the relationship between clinical
      status of MS and cytokine levels in eight patients with MS who were followed
      through pregnancy and after delivery. Peripheral blood lymphocytes from these
      women were stimulated with a mitogen at different time points during and after
      gestation and the levels of Th1 cytokines (IFNgamma, TNFalpha) and Th2 cytokines
      (IL-4, IL-10) were estimated by ELISA. It was established that six of the eight
      MS patients studied showed a distinct shift from a Th2 cytokine bias during
      pregnancy towards a Th1 cytokine bias after delivery. These results suggest a
      possible association between decreased incidence of exacerbation of MS in
      pregnancy and a pregnancy-induced shift towards Th2 cytokine bias.

PMID- 15240192
TI  - Evidence of axonal damage in human acute demyelinating diseases.
AB  - Substantial axon damage, detected by immunostaining for beta amyloid precursor
      protein (betaAPP) has been demonstrated in acute demyelinating lesions in
      multiple sclerosis. AIMS: The present study aimed to determine if this was also
      the case in the other human acute demyelinating diseases, acute hemorrhagic
      leucoencephalitis (AHLE), acute disseminated encephalomyelitis (ADEM) and central
      pontine myelinolysis (CPM). METHODS: BetaAPP immunostaining was used as a marker
      of axonal damage in autopsy material from these conditions. RESULTS: Axonal
      damage was detected in all these conditions. Its extent varied within and between
      them. Axonal damage was largely confined to tissue adjacent to veins and venules
      in AHLE and ADEM but was unrelated to proximity to these vessels in CPM.
      CONCLUSION: Substantial axon damage occurs in fatal cases of AHLE, ADEM and CPM.

PMID- 15240193
TI  - HTLV-I associated myelopathy/tropical spastic paraparesis in a 7-year-old boy
      associated with infective dermatitis.
AB  - HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic
      myelopathy characterized by a slowly progressive spastic paraparesis and
      sphincter disturbances beginning in adulthood. Only eight well-documented cases
      occurring in childhood and adolescence have been described. Infective dermatitis
      associated to the HTLV-I (IDH) is a chronic eczema of childhood occurring in
      vertically infected carriers. Here we describe a 7-year-old boy with HAM/TSP and
      IDH. The neurological manifestations were spastic gait, hyperreflexia of lower
      limbs, clonus and bilateral Babinski's sign. High levels of HTLV-I antibodies in
      the serum and in the cerebrospinal fluid were observed. The association of these
      two diseases and the early onset of HAM/TSP are probably related to a strong
      humoral anti-HTLV-I response.

PMID- 15240194
TI  - Comfort care in severely disabled multiple sclerosis patients.
AB  - Comfort may be considered as the material aspect of well-being, and its
      limitation, defined as discomfort, exacerbates both the patient's and caregivers'
      difficulties. Discomfort results from the interaction of a patient's environment,
      treatment, and from the nature and severity of elementary deficits, such as
      spasticity, ranges of motion, pain, postural disorders, motor deficit and
      fatigue, bladder problems, insufficient ventilatory control, and also
      psychological difficulties. Although discomfort reduction may represent a major
      challenge in disabled persons, discomfort is usually underestimated in the
      assessment of deficiencies, disabilities, handicap, and even in quality of life
      (QOL) estimations. In this paper, we explain why discomfort may be a crucial
      problem in severe multiple sclerosis (MS) and argue for a systematic assessment
      of discomfort in the follow-up of the disease, especially in the following
      domains: dressing, washing, maintaining posture in a wheelchair and bed, food
      intake, mastication and swallowing, bowel control, urinary and feces emission,
      and also sexual life. The way to enhance comfort in MS patients is then analyzed.

PMID- 15240195
TI  - Maintained regulation of polyamines in spinal cord from patients with amyotrophic
      lateral sclerosis.
AB  - Levels of the polyamines putrescine, spermidine, and spermine were investigated
      in postmortem spinal cord from seven patients with amyotrophic lateral sclerosis
      (ALS) and seven control subjects. The method consisted of precolumn
      derivatization of the polyamines, followed by high-performance liquid
      chromatography (HPLC) analysis and fluorescence detection. The stability of the
      polyamines was examined in rat spinal cord during the interval of 0-36 h
      postmortem. The levels of putrescine, spermidine, and spermine increased by 32%,
      15%, and 2%, respectively. Polyamine levels did not differ significantly between
      the ALS group and the control group, suggesting a maintained regulation of
      polyamines in the end stage of the disease. However, an effect of gender on the
      levels of spermidine and spermine was observed. Levels of spermidine and spermine
      in the ventral horn region of female ALS patients were significantly higher in
      comparison with the same region of the male ALS group (p<0.05). The female ALS
      group also presented significantly higher levels of spermidine in comparison with
      female controls (p<0.05).

PMID- 15240196
TI  - Effect of a 0.5-T static magnetic field on conduction in guinea pig spinal cord.
AB  - Compound-evoked potentials were recorded from excised adult guinea pig spinal
      cords before, during, and following exposure to a 0.5-T static magnetic field
      (SMF). There was no change in response latency during exposure but there was a
      small, statistically significant, decrease in amplitude. Maximum effect was
      evident 1 to 2 min after the field was turned on with return to baseline within 1
      min after the field was turned off. These results may be explained by a
      conduction block in the small axon subpopulation due to the effect of static
      magnetic fields on voltage-activated sodium channels. The relative selectivity of
      the field is believed to occur because of the relatively greater number of sodium
      channels present in smaller axons.

PMID- 15240197
TI  - Clinico-radiologic correlation in unilateral and bilateral hemifacial spasm.
AB  - INTRODUCTION: Bilateral hemifacial spasm (HFS) is rare. Clinico-radiologic
      correlates utilizing advanced imaging techniques have not been systematically
      examined in bilateral HFS. The prevalence of bilateral HFS in an Asian population
      has not been clarified. OBJECTIVES: We examined the prevalence and clinico
      radiologic correlates of bilateral HFS in a clinic-based cohort and compared the
      clinical characteristics of unilateral HFS patients with and without
      contralateral neurovascular contact (NVC) in HFS. METHODS: Patients clinically
      diagnosed with HFS were examined for bilateral symptoms. Imaging analysis
      involved the utilization of reformatted, multi-planar three-dimensional time-of
      flight magnetic resonance angiography (3D-TOF MRA), and constructive interference
      at steady state (CISS-MR) sequences. The clinical and imaging data was compared
      between HFS with and without NVC. RESULTS: Amongst 162 consecutive HFS patients,
      2 (1.6%) had bilateral symptoms. Both patients had unilateral onset followed by
      bilateral and asynchronous facial contractions. The contralateral side of the
      face began to twitch at a mean of 1.5 years later. MRI/A revealed significant NVC
      of the root exit zone (REZ) of the facial nerve on the ipsilateral side with mild
      NVC contralaterally. The degree of NVC correlated with the clinical severity of
      the patients' symptoms. MRI/A analysis of 40 HFS patients with unilateral
      symptoms demonstrated NVC on the contralateral side in six patients (15%). The
      mean age and duration of symptoms were not different between HFS patients with
      and without contralateral NVC. CONCLUSIONS: We demonstrated clinico-radiologic
      correlation between the clinical severity and the degree of NVC at the REZ of the
      facial nerve in bilateral HFS. Amongst unilateral HFS, there was no significant
      difference clinically between those with and without contralateral NVC. The low
      1.6% prevalence of bilateral HFS in our Asian cohort was compatible with the rare
      prevalence in other ethnic populations.

PMID- 15240198
TI  - Time-dependent cytokine deviation toward the Th2 side in Japanese multiple
      sclerosis patients with interferon beta-1b.
AB  - To address the immune mechanism sustaining interferon beta (IFNbeta) efficacy in
      multiple sclerosis (MS), we longitudinally analyzed expressions of IFN-gamma, IL
      4, IL-5 and IL-13 in CD4+ T cells and CD8+ T cells in 22 Japanese MS patients (16
      patients with conventional MS and 6 with opticospinal MS) undergoing IFNbeta
      using flow cytometry. During the 48-week observation period, five opticospinal MS
      patients (83%) relapsed compared to only four conventional MS patients (25%); the
      frequency of relapsed patients was significantly higher in the former (p=0.046).
      The effects of IFNbeta on individual cytokines were time-dependent and altered
      cytokine productions were particularly evident in CD4+ rather than CD8+ T cells.
      A decreased intracellular IFN-gamma/IL-4 ratio in CD4+ T cells was thus evident
      soon after the initiation of therapy, and persisted for the entire 1 year follow
      up period, regardless of whether or not the patient relapsed (p<0.01). IFNbeta
      treatment resulted in a rapid increase in the percentage of IFN-gamma- IL-4+ and
      IL-13+ CD4+ T cells 1 week after the initiation of therapy and high values were
      sustained for 6 months but declined to the baseline over 1 year. Later, the
      percentage of IFN-gamma+ IL-4- CD4+ T cells decreased significantly from weeks 24
      through 48 of therapy (p<0.01). When comparisons with the pretreatment values
      were made for each subtype of MS, a significant reduction of IFN-gamma+ IL-4-
      CD4+ T cell percentages was shown in conventional MS (p<0.0001), but not in
      opticospinal MS. Moreover, when such a comparison was made by the presence or
      absence of relapse during therapy, a significant reduction of IFN-gamma+ IL-4-
      CD4+ T cell percentages was observed in MS patients without relapse (p<0.01).
      Thus, a reduction of IFN-gamma+ IL-4- CD4+ T cell percentages in the late phase
      of therapy is considered important for reducing relapse in conventional MS. When
      the expression patterns of IFN-gamma, IL-4, IL-5 and IL-13 in CD4+ T cells and
      CD8+ T cells were compared between patients with and without relapse during
      therapy, the only significant difference was an increase in the IL-13+ CD4+ T
      cell percentages in patients with relapse compared to those without (p<0.05). The
      results indicate that in CD4+ T cells IL-4 was preferentially up-regulated in the
      early course and IFN-gamma was down-regulated in the late phase of IFNbeta
      therapy. The net effect of IFNbeta on the immune balance was entirely toward type
      2 immune deviation, possibly contributing to its beneficial effects on MS.

PMID- 15240199
TI  - Pupillography refines the diagnosis of diabetic autonomic neuropathy.
AB  - Although diabetic autonomic neuropathy involves most organs, diagnosis is largely
      based on cardiovascular tests. Light reflex pupillography (LRP) non-invasively
      evaluates pupillary autonomic function. We tested whether LRP demonstrates
      autonomic pupillary dysfunction in diabetics independently from cardiac autonomic
      neuropathy (CAN) or peripheral neuropathy (PN). In 36 type-II diabetics (39-84
      years) and 36 controls (35-78 years), we performed LRP. We determined diameter
      (PD), early and late re-dilation velocities (DV) as sympathetic parameters and
      reflex amplitude (RA) and constriction velocity (CV) as parasympathetic pupillary
      indices. We assessed the frequency of CAN using heart rate variability tests and
      evaluated the frequency of PN using neurological examination, nerve conduction
      studies, thermal and vibratory threshold determination. Twenty-eight (77.8%)
      patients had abnormal pupillography results, but only 20 patients (56%) had signs
      of PN or CAN. In nine patients with PN, only pupillography identified autonomic
      neuropathy. Four patients had pupillary dysfunction but no CAN or PN. In
      comparison to controls, patients had reduced PD, late DV, RA and CV indicating
      sympathetic and parasympathetic dysfunction. The incidence and severity of
      pupillary abnormalities did not differ between patients with and without CAN or
      PN. LRP demonstrates sympathetic and parasympathetic pupillary dysfunction
      independently from PN or CAN and thus refines the diagnosis of autonomic
      neuropathy in type-II diabetics.

PMID- 15240200
TI  - Is cerebral angiography redundant in undetermined cause of stroke in patients
      below 50 years when the stroke is lacunar?
AB  - BACKGROUND: In the diagnostic work-up of young stroke patients angiography is
      still considered as mandatory to identify otherwise undetected causes of stroke.
      We hypothesized that stroke cause is more heterogeneous among patients with a
      territorial infarct, whereas in lacunar stroke it is generally small vessel
      disease. Therefore, angiography yields more often a specific stroke cause in
      territorial than in lacunar infarct patients. METHODS: Angiograms of 39 lacunar
      and 41 territorial brain infarct patients, aged between 14 and 51 years, and who
      had unexplained stroke cause, were evaluated. RESULTS: 1 of the 39 lacunar (3%),
      and 18 of the 41 territorial stroke patients (44%) had abnormal angiogram: odds
      ratio 0.03, 95% confidence interval: 0.01-0.017. The predictive value of lacunar
      stroke for a normal angiogram was 97%. CONCLUSION: When undetermined cause of
      stroke in young patients is lacunar, it is highly predictive for a normal
      angiogram. Our data may be of value in deciding on performing angiography in
      individual young stroke patients, depending on whether the stroke is territorial
      or lacunar.

PMID- 15240201
TI  - Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced
      salivation and tremor.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of 12 subunits
      (alpha2-alpha10 and beta2-beta4). alpha5 Subunits, expressed throughout the
      central nervous system (CNS) and the autonomic nervous system (ANS), possess
      unique pharmacological properties. The effects of oxotremorine (OXO) on autonomic
      functions and tremor were examined in mice lacking alpha5 nAChR subunits (alpha5
      /-) and compared with those in wild-type (WT) control mice. The alpha5-/- mice
      showed significantly increased salivation and tremor responses to OXO. The
      hypothermia, bradycardia and defecation induced by OXO were of similar magnitudes
      in the two mouse strains. The enhanced OXO effects in alpha5-/- mice indicate
      inhibitory effects of alpha5 subunits in autonomic ganglia, and support the
      participation of these subunits in cholinergic transmission in autonomic ganglia.

PMID- 15240202
TI  - Muscle MRI findings of X-linked spinal and bulbar muscular atrophy.
AB  - We report here muscle MRI findings of the lower limb in X-linked spinal and
      bulbar muscular atrophy (SBMA). T1-weighted imaging of muscle MRI disclosed that
      the thigh muscles, including the semimembranosus, biceps femoris longus and the
      vastus lateralis muscles, showed high intensity signals with atrophy. Contrarily,
      the sartorius, gracilis and rectus femoris muscles were comparably preserved. Not
      only the thigh muscles, but also the calf muscles including the gastrocnemius
      medialis and lateralis, and soleus muscles showed high intensity signals. In
      amyotrophic lateral sclerosis (ALS), the leg muscles are generally atrophic, but
      the selective pattern of fatty degeneration, seen in SBMA was not observed.
      Muscle MRI is a useful method of estimating the distribution and severity of SBMA
      in affected muscles.

PMID- 15240203
TI  - Computer-aided retraining of memory and attention in people with multiple
      sclerosis: a randomized, double-blind controlled trial.
AB  - CONTEXT: Cognitive compromise is one of the main contributing factors to activity
      and participation restrictions in people with multiple sclerosis (MS). Computer
      aided programs are used for retraining memory and attention, but data on the
      efficacy of these interventions are scarce. OBJECTIVE: To assess the efficacy of
      computer-aided retraining of memory and attention in people with MS impaired in
      these abilities. DESIGN AND SETTING: Randomized, double-blind, controlled trial.
      PARTICIPANTS: Outpatients (n=82) with subjective complaints of poor attention or
      memory, confirmed by a score <80th percentile in at least two tests of the Brief
      Repeatable Battery of Neuropsychological Tests (BRBNT). INTERVENTIONS:
      Participants were randomized to two computer-assisted retraining interventions:
      memory and attention (study arm), and visuo-constructional and visuo-motor
      coordination (control arm). Both groups received 16 training sessions over 8
      weeks. OUTCOME MEASURES: Improvement of 20% or more in at least two BRBNT test
      scores at 8 weeks compared to baseline (primary end point). Changes in depression
      and health-related quality of life. RESULTS: An improvement occurred in 45% of
      study patients vs. 43% of control patients (odds ratio 1.07, 95% confidence
      interval 0.44-2.64). The study treatment was better than the control treatment
      only on the word list generation test (p=0.016). CONCLUSIONS: This trial does not
      support the efficacy of specific memory and attention retraining in MS.

PMID- 15240204
TI  - Sudden deafness with vertigo as a sole manifestation of anterior inferior
      cerebellar artery infarction.
AB  - Sudden deafness without associated neurological symptoms and signs is typically
      attributed to a viral inflammation of the labyrinth. Although sudden deafness
      occurs with anterior inferior cerebellar artery (AICA) infarction, the deafness
      is usually associated with other brainstem or cerebellum signs such as crossed
      sensory loss, lateral gaze palsy, facial palsy, Horner syndrome or cerebellar
      dysmetria. An 84-year-old woman suddenly developed right-sided tinnitus, hearing
      loss, vertigo and vomiting. Audiometry and electronystagmography documented
      absent auditory and vestibular function on the right side. T2-weighted and
      diffusion-weighted MRI showed a tiny infarct in the right lateral inferior
      pontine tegmentum. AICA occlusion can cause sudden deafness and vertigo without
      brainstem or cerebellar signs.

PMID- 15240205
TI  - Renal cholesterol embolism in patients with carotid stenosis: a severe and
      underdiagnosed complication following cerebrovascular procedures.
AB  - Here, we report two cases with rapidly progressive renal failure, caused by
      cholesterol crystal embolism (CCE), after an angiography for carotid artery
      stenosis. The diagnosis was determined by histological examination and from
      clinical symptoms, including livedo reticularis and eosinophilia. Neurologists
      and neuroradiologists tend to underdiagnose CCE, which results from the same
      atherosclerotic risk factors as cerebrovascular disease. We need to understand
      more about CCE and identify its unique clinical symptoms to enable an early
      diagnosis and treatment.

PMID- 15240206
TI  - University of alabama school of medicine.

PMID- 15240207
TI  - Albert Einstein College of Medicine of Yeshiva University.

PMID- 15240208
TI  - University of Arizona College of Medicine.

PMID- 15240209
TI  - University of California, Irvine, College of Medicine.

PMID- 15240210
TI  - University of California, Los Angeles, David Geffen School of Medicine at UCLA.

PMID- 15240211
TI  - University of California, San Francisco, School of Medicine.

PMID- 15240212
TI  - University of Cincinnati College of Medicine.

PMID- 15240213
TI  - Columbia University College of Physicians and Surgeons.

PMID- 15240214
TI  - University of Connecticut School of Medicine.

PMID- 15240215
TI  - Duke University School of Medicine.

PMID- 15240216
TI  - Georgetown University School of Medicine.

PMID- 15240217
TI  - Southern Illinois University School of Medicine.

PMID- 15240218
TI  - Indiana University School of Medicine.

PMID- 15240219
TI  - Jefferson Medical College of Thomas Jefferson University.

PMID- 15240220
TI  - Johns Hopkins University School of Medicine.

PMID- 15240221
TI  - University of Kansas School of Medicine.

PMID- 15240222
TI  - Louisiana State University Health Sciences Center in Shreveport.

PMID- 15240223
TI  - University of Louisville School of Medicine.

PMID- 15240224
TI  - University of Massachusetts Medical School.

PMID- 15240225
TI  - Meharry Medical College School of Medicine.

PMID- 15240226
TI  - University of Miami School of Medicine.

PMID- 15240227
TI  - University of Minnesota Medical School-Twin Cities.

PMID- 15240228
TI  - University of Missouri-Columbia School of Medicine.

PMID- 15240229
TI  - University of Missouri-Kansas City School of Medicine.

PMID- 15240230
TI  - Mount Sinai School of Medicine.

PMID- 15240231
TI  - University of Nebraska College of Medicine.

PMID- 15240232
TI  - University of New Mexico School of Medicine.

PMID- 15240233
TI  - State University of New York Upstate Medical University College of Medicine.

PMID- 15240234
TI  - University of North Carolina at Chapel Hill School of Medicine.

PMID- 15240235
TI  - Ohio State University College of Medicine and Public Health.

PMID- 15240236
TI  - University of Pittsburgh School of Medicine.

PMID- 15240237
TI  - University of South Carolina School of Medicine.

PMID- 15240238
TI  - Saint Louis University School of Medicine.

PMID- 15240239
TI  - East Tennessee State University James H Quillen College of Medicine.

PMID- 15240240
TI  - University of Texas Medical Branch at Galveston.

PMID- 15240241
TI  - University of Texas Health Science Center at San Antonio.

PMID- 15240242
TI  - Texas Tech University Health Sciences Center School of Medicine.

PMID- 15240243
TI  - Wayne State University School of Medicine.

PMID- 15240244
TI  - Medical College of Wisconsin.

PMID- 15240245
TI  - University of Wisconsin Medical School.

PMID- 15240246
TI  - A thematic summary of the geriatrics curricula at 40 U S Medical schools.

PMID- 15240247
TI  - Characteristics of geriatrics curricula at 40 U.S. Medical schools.

PMID- 15240249
TI  - Thioesterase II of Escherichia coli plays an important role in 3-hydroxydecanoic
      acid production.
AB  - 3-Hydroxydecanoic acid (3HD) was produced in Escherichia coli by mobilizing (R)-3
      hydroxydecanoyl-acyl carrier protein-coenzyme A transacylase (PhaG, encoded by
      the phaG gene). By employing an isogenic tesB (encoding thioesterase II)-negative
      knockout E. coli strain, CH01, it was found that the expressions of tesB and phaG
      can up-regulate each other. In addition, 3HD was synthesized from glucose or
      fructose by recombinant E. coli harboring phaG and tesB. This study supports the
      hypothesis that the physiological role of thioesterase II in E. coli is to
      prevent the abnormal accumulation of intracellular acyl-coenzyme A.

PMID- 15240248
TI  - Detection and quantification of gene expression in environmental bacteriology.

PMID- 15240250
TI  - Oxidation of benzene to phenol, catechol, and 1,2,3-trihydroxybenzene by toluene
      4-monooxygenase of Pseudomonas mendocina KR1 and toluene 3-monooxygenase of
      Ralstonia pickettii PKO1.
AB  - Aromatic hydroxylations are important bacterial metabolic processes but are
      difficult to perform using traditional chemical synthesis, so to use a biological
      catalyst to convert the priority pollutant benzene into industrially relevant
      intermediates, benzene oxidation was investigated. It was discovered that toluene
      4-monooxygenase (T4MO) of Pseudomonas mendocina KR1, toluene 3-monooxygenase
      (T3MO) of Ralstonia pickettii PKO1, and toluene ortho-monooxygenase (TOM) of
      Burkholderia cepacia G4 convert benzene to phenol, catechol, and 1,2,3
      trihydroxybenzene by successive hydroxylations. At a concentration of 165 microM
      and under the control of a constitutive lac promoter, Escherichia coli
      TG1/pBS(Kan)T4MO expressing T4MO formed phenol from benzene at 19 +/- 1.6
      nmol/min/mg of protein, catechol from phenol at 13.6 +/- 0.3 nmol/min/mg of
      protein, and 1,2,3-trihydroxybenzene from catechol at 2.5 +/- 0.5nmol/min/mg of
      protein. The catechol and 1,2,3-trihydroxybenzene products were identified by
      both high-pressure liquid chromatography and mass spectrometry. When analogous
      plasmid constructs were used, E. coli TG1/pBS(Kan)T3MO expressing T3MO formed
      phenol, catechol, and 1,2,3-trihydroxybenzene at rates of 3 +/- 1, 3.1 +/- 0.3,
      and 0.26 +/- 0.09 nmol/min/mg of protein, respectively, and E. coli
      TG1/pBS(Kan)TOM expressing TOM formed 1,2,3-trihydroxybenzene at a rate of 1.7 +/
      0.3 nmol/min/mg of protein (phenol and catechol formation rates were 0.89 +/-
      0.07 and 1.5 +/- 0.3 nmol/min/mg of protein, respectively). Hence, the rates of
      synthesis of catechol by both T3MO and T4MO and the 1,2,3-trihydroxybenzene
      formation rate by TOM were found to be comparable to the rates of oxidation of
      the natural substrate toluene for these enzymes (10.0 +/- 0.8, 4.0 +/- 0.6, and
      2.4 +/- 0.3 nmol/min/mg of protein for T4MO, T3MO, and TOM, respectively, at a
      toluene concentration of 165 microM).

PMID- 15240251
TI  - Specific response of a novel and abundant Lactobacillus amylovorus-like phylotype
      to dietary prebiotics in the guts of weaning piglets.
AB  - Using 16S rRNA gene-based approaches, we analyzed the responses of ileal and
      colonic bacterial communities of weaning piglets to dietary addition of four
      fermentable carbohydrates (inulin, lactulose, wheat starch, and sugar beet pulp).
      An enriched diet and a control diet lacking these fermentable carbohydrates were
      fed to piglets for 4 days (n = 48), and 10 days (n = 48), and the lumen
      associated microbiota were compared using denaturing gradient gel electrophoresis
      (DGGE) analysis of amplified 16S rRNA genes. Bacterial diversities in the ileal
      and colonic samples were measured by assessing the number of DGGE bands and the
      Shannon index of diversity. A higher number of DGGE bands in the colon (24.2 +/-
      5.5) than in the ileum (9.7 +/- 4.2) was observed in all samples. In addition,
      significantly higher diversity, as measured by DGGE fingerprint analysis, was
      detected in the colonic microbial community of weaning piglets fed the
      fermentable-carbohydrate-enriched diet for 10 days than in the control. Selected
      samples from the ileal and colonic lumens were also investigated using
      fluorescent in situ hybridization (FISH) and cloning and sequencing of the 16S
      rRNA gene. This revealed a prevalence of Lactobacillus reuteri in the ileum and
      Lactobacillus amylovorus-like populations in the ileum and the colon in the
      piglets fed with fermentable carbohydrates. Newly developed oligonucleotide
      probes targeting these phylotypes allowed their rapid detection and
      quantification in the ileum and colon by FISH. The results indicate that addition
      of fermentable carbohydrates supports the growth of specific lactobacilli in the
      ilea and colons of weaning piglets.

PMID- 15240252
TI  - Purification and characterization of two distinct metalloproteases secreted by
      the entomopathogenic bacterium Photorhabdus sp. strain Az29.
AB  - Photorhabdus sp. strain Az29 is symbiotic with an Azorean nematode of the genus
      Heterorhabditis in a complex that is highly virulent to insects even at low
      temperatures. The virulence of the bacteria is mainly attributed to toxins and
      bacterial enzymes secreted during parasitism. The bacteria secrete proteases
      during growth, with a peak at the end of the exponential growth phase. Protease
      secretion was higher in cultures growing at lower temperatures. At 10 degrees C
      the activity was highest and remained constant for over 7 days, whereas at 23 and
      28 degrees C it showed a steady decrease. Two proteases, PrtA and PrtS, that are
      produced in the growth medium were purified by liquid chromatography. PrtA was
      inhibited by 1,10-phenantroline and by EDTA and had a molecular mass of 56 kDa
      and an optimal activity at pH 9 and 50 degrees C. Sequences of three peptides of
      PrtA showed strong homologies with alkaline metalloproteases from Photorhabdus
      temperata K122 and Photorhabdus luminescens W14. Peptide PrtA-36 contained the
      residues characteristic of metzincins, known to be involved in bacterial
      virulence. In vitro, PrtA inhibited antibacterial factors of inoculated
      Lepidoptera and of cecropins A and B. PrtS had a molecular mass of 38 kDa and was
      inhibited by 1,10-phenanthroline but not by EDTA. Its activity ranged between 10
      and 80 degrees C and was optimal at pH 7 and 50 degrees C. PrtS also destroyed
      insect antibacterial factors. Three fragments of PrtS showed homology with a
      putative metalloprotease of P. luminescens TTO1. Polyclonal antibody raised
      against PrtA did not recognize PrtS, showing they are distinct molecules.

PMID- 15240253
TI  - Thermus thermophilus as a cell factory for the production of a thermophilic Mn
      dependent catalase which fails to be synthesized in an active form in Escherichia
      coli.
AB  - Thermostable Mn-dependent catalases are promising enzymes in biotechnological
      applications as H(2)O(2)-detoxifying systems. We cloned the genes encoding Mn
      dependent catalases from Thermus thermophilus HB27 and HB8 and a less
      thermostable mutant carrying two amino acid replacements (M129V and E293G). When
      the wild-type and mutant genes were overexpressed in Escherichia coli, unmodified
      or six-His-tagged proteins of the expected size were overproduced as inactive
      proteins. Several attempts to obtain active forms or to activate the overproduced
      proteins were unsuccessful, even when soluble and thermostable proteins were
      used. Therefore, a requirement for a Thermus-specific activation factor was
      suggested. To overcome this problem, the Mn-dependent catalase genes were
      overexpressed directly in T. thermophilus under the control of the Pnar promoter.
      This promoter belongs to a respiratory nitrate reductase from of T. thermophilus
      HB8, whose transcription is activated by the combined action of nitrate and
      anoxia. Upon induction in T. thermophilus HB8, a 20- to 30-fold increase in
      catalase specific activity was observed, whereas a 90- to 110-fold increase was
      detected when the laboratory strain T. thermophilus HB27::nar was used as the
      host. The thermostability of the overproduced wild-type catalase was identical to
      that previously reported for the native enzyme, whereas decreased stability was
      detected for the mutant derivative. Therefore, our results validate the use of T.
      thermophilus as an alternative cell factory for the overproduction of
      thermophilic proteins that fail to be expressed in well-known mesophilic hosts.

PMID- 15240254
TI  - Impact of heterologous expression of Escherichia coli UDP-glucose
      pyrophosphorylase on trehalose and glycogen synthesis in Corynebacterium
      glutamicum.
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
      improved strains of the gram-positive bacterium Corynebacterium glutamicum. This
      microorganism synthesizes trehalose through two major pathways, OtsBA and TreYZ,
      by using UDP-glucose and ADP-glucose, respectively, as the glucosyl donors. In
      this paper we describe improvement of the UDP-glucose supply through heterologous
      expression in C. glutamicum of the UDP-glucose pyrophosphorylase gene from
      Escherichia coli, either expressed alone or coexpressed with the E. coli ots
      genes (galU otsBA synthetic operon). The impact of such expression on trehalose
      accumulation and excretion, glycogen accumulation, and the growth pattern of new
      recombinant strains is described. Expression of the galU otsBA synthetic operon
      resulted in a sixfold increase in the accumulated and excreted trehalose relative
      to that in a wild-type strain. Surprisingly, single expression of galU also
      resulted in an increase in the accumulated trehalose. This increase in trehalose
      synthesis was abolished upon deletion of the TreYZ pathway. These results proved
      that UDP-glucose has an important role not only in the OtsBA pathway but also in
      the TreYZ pathway.

PMID- 15240255
TI  - Ability of thermophilic lactic acid bacteria to produce aroma compounds from
      amino acids.
AB  - Although a large number of key odorants of Swiss-type cheese result from amino
      acid catabolism, the amino acid catabolic pathways in the bacteria present in
      these cheeses are not well known. In this study, we compared the in vitro
      abilities of Lactobacillus delbrueckii subsp. lactis, Lactobacillus helveticus,
      and Streptococcus thermophilus to produce aroma compounds from three amino acids,
      leucine, phenylalanine, and methionine, under mid-pH conditions of cheese
      ripening (pH 5.5), and we investigated the catabolic pathways used by these
      bacteria. In the three lactic acid bacterial species, amino acid catabolism was
      initiated by a transamination step, which requires the presence of an alpha-keto
      acid such as alpha-ketoglutarate (alpha-KG) as the amino group acceptor, and
      produced alpha-keto acids. Only S. thermophilus exhibited glutamate dehydrogenase
      activity, which produces alpha-KG from glutamate, and consequently only S.
      thermophilus was capable of catabolizing amino acids in the reaction medium
      without alpha-KG addition. In the presence of alpha-KG, lactobacilli produced
      much more varied aroma compounds such as acids, aldehydes, and alcohols than S.
      thermophilus, which mainly produced alpha-keto acids and a small amount of
      hydroxy acids and acids. L. helveticus mainly produced acids from phenylalanine
      and leucine, while L. delbrueckii subsp. lactis produced larger amounts of
      alcohols and/or aldehydes. Formation of aldehydes, alcohols, and acids from alpha
      keto acids by L. delbrueckii subsp. lactis mainly results from the action of an
      alpha-keto acid decarboxylase, which produces aldehydes that are then oxidized or
      reduced to acids or alcohols. In contrast, the enzyme involved in the alpha-keto
      acid conversion to acids in L. helveticus and S. thermophilus is an alpha-keto
      acid dehydrogenase that produces acyl coenzymes A.

PMID- 15240256
TI  - Accurate estimation of viral abundance by epifluorescence microscopy.
AB  - Virus enumeration by epifluorescence microscopy (EFM) is routinely done on
      preserved, refrigerated samples. Concerns about obtaining accurate and
      reproducible estimates led us to examine procedures for counting viruses by EFM.
      Our results indicate that aldehyde fixation results in rapid decreases in viral
      abundance. By 1 h postfixation, the abundance dropped by 16.4% +/- 5.2% (n = 6),
      and by 4 h, the abundance was 20 to 35% lower. The average loss rates for
      glutaraldehyde- and formaldehyde-fixed samples over the first 2 h were 0.12 and
      0.13 h(-1), respectively. By 16 days, viral abundance had decreased by 72%
      (standard deviation, 6%; n = 6). Aldehyde fixation of samples followed by storage
      at 4 degrees C, for even a few hours, resulted in large underestimates of viral
      abundance. The viral loss rates were not constant, and in glutaraldehyde- and
      formaldehyde-fixed samples they decreased from 0.13 and 0.17 h(-1) during the
      first hour to 0.01 h(-1) between 24 and 48 h. Although decay rates changed over
      time, the abundance was predicted by using separate models to describe decay over
      the first 8 h and decay beyond 8 h. Accurate estimates of abundance were easily
      made with unfixed samples stained with Yo-Pro-1, SYBR Green I, or SYBR Gold, and
      slides could be stored at -20 degrees C for at least 2 weeks or, for Yo-Pro-1, at
      least 1 year. If essential, samples can be fixed and flash frozen in liquid
      nitrogen upon collection and stored at -86 degrees C. Determinations performed
      with fixed samples result in large underestimates of abundance unless slides are
      made immediately or samples are flash frozen. If protocols outlined in this paper
      are followed, EFM yields accurate estimates of viral abundance.

PMID- 15240257
TI  - The P450 monooxygenase BcABA1 is essential for abscisic acid biosynthesis in
      Botrytis cinerea.
AB  - The phytopathogenic ascomycete Botrytis cinerea is known to produce abscisic acid
      (ABA), which is thought to be involved in host-pathogen interaction. Biochemical
      analyses had previously shown that, in contrast to higher plants, the fungal ABA
      biosynthesis probably does not proceed via carotenoids but involves direct
      cyclization of farnesyl diphosphate and subsequent oxidation steps. We present
      here evidence that this "direct" pathway is indeed the only one used by an ABA
      overproducing strain of B. cinerea. Targeted inactivation of the gene bccpr1
      encoding a cytochrome P450 oxidoreductase reduced the ABA production
      significantly, proving the involvement of P450 monooxygenases in the pathway.
      Expression analysis of 28 different putative P450 monooxygenase genes revealed
      two that were induced under ABA biosynthesis conditions. Targeted inactivation
      showed that one of these, bcaba1, is essential for ABA biosynthesis: DeltaBcaba1
      mutants contained no residual ABA. Thus, bcaba1 represents the first identified
      fungal ABA biosynthetic gene.

PMID- 15240258
TI  - Longitudinal study of Campylobacter jejuni bacteriophages and their hosts from
      broiler chickens.
AB  - A longitudinal study of bacteriophages and their hosts was carried out at a
      broiler house that had been identified as having a population of Campylobacter
      specific bacteriophages. Cloacal and excreta samples were collected from three
      successive broiler flocks reared in the same barn. Campylobacter jejuni was
      isolated from each flock, whereas bacteriophages could be isolated from flocks 1
      and 2 but were not isolated from flock 3. The bacteriophages isolated from flocks
      1 and 2 were closely related to each other in terms of host range, morphology,
      genome size, and genetic content. All Campylobacter isolates from flock 1 were
      genotypically indistinguishable by pulsed-field gel electrophoresis (PFGE). PFGE
      and multilocus sequence typing indicated that this C. jejuni type was maintained
      from flock 1 to flock 2 but was largely superseded by three genetically distinct
      C. jejuni types insensitive to the resident bacteriophages. All isolates from the
      third batch of birds were insensitive to bacteriophages and genotypically
      distinct. These results are significant because this is the first study of an
      environmental population of C. jejuni bacteriophages and their influence on the
      Campylobacter populations of broiler house chickens. The role of developing
      bacteriophage resistance was investigated as this is a possible obstacle to the
      use of bacteriophage therapy to reduce the numbers of campylobacters in chickens.
      In this broiler house succession was largely due to incursion of new genotypes
      rather than to de novo development of resistance.

PMID- 15240260
TI  - Isolation and characterization of Micromonospora phage PhiHAU8 and development
      into a phasmid.
AB  - PhiHAU8, a temperate Micromonospora phage, which is capable of infecting
      Micromonospora sp. strains 40027 and A-M-01, was isolated. The PhiHAU8 virion has
      a polyhedral head and a flexible tail and has a small genome (ca. 42.5 kb) with
      double-stranded DNA and cohesive ends. PhiHAU8 was most stable at 4 degrees C in
      Difco nutrient broth within a pH range of 6 to 12. PhiHAU8 plaque formation on
      Micromonospora sp. strain 40027 was optimal with 32 mM Ca(2+) and 30 mM Mg(2+). A
      lysogen, LXH8, was isolated from turbid plaques, and a phasmid derivative that
      functions as a lambda cosmid vector in Escherichia coli and as a phage in
      Micromonospora sp. strain 40027 was constructed. Pulsed-field gel electrophoresis
      of AseI-digested total DNA showed that PhiHAU8 DNA integrates into the 500-kb
      AseI fragment of Micromonospora sp. strain 40027.

PMID- 15240259
TI  - Comparison of Euryarchaea strains in the guts and food-soil of the soil-feeding
      termite Cubitermes fungifaber across different soil types.
AB  - Termites are an important component of tropical soil communities and have a
      significant effect on the structure and nutrient content of soil. Digestion in
      termites is related to gut structure, gut physicochemical conditions, and gut
      symbiotic microbiota. Here we describe the use of 16S rRNA gene sequencing and
      terminal-restriction fragment length polymorphism (T-RFLP) analysis to examine
      methanogenic archaea (MA) in the guts and food-soil of the soil-feeder Cubitermes
      fungifaber Sjostedt across a range of soil types. If these MA are strictly
      vertically inherited, then the MA in guts should be the same in all individuals
      even if the soils differ across sites. In contrast, gut MA should reflect what is
      present in soil if populations are merely a reflection of what is ingested as the
      insects forage. We show clear differences between the euryarchaeal communities in
      termite guts and in food-soils from five different sites. Analysis of 16S rRNA
      gene clones indicated little overlap between the gut and soil communities. Gut
      clones were related to a termite-derived Methanomicrobiales cluster, to
      Methanobrevibacter and, surprisingly, to the haloalkaliphile Natronococcus. Soil
      clones clustered with Methanosarcina, Methanomicrococcus, or rice cluster I. T
      RFLP analysis indicated that the archaeal communities in the soil samples
      differed from site to site, whereas those in termite guts were similar between
      sites. There was some overlap between the gut and soil communities, but these may
      represent transient populations in either guts or soil. Our data do not support
      the hypothesis that termite gut MA are derived from their food-soil but also do
      not support a purely vertical transmission of gut microflora.

PMID- 15240261
TI  - Disruption of the subtilase gene, albin1, in Ophiostoma piliferum.
AB  - Wood sapstaining fungi produce multiple proteases that break down wood protein.
      Three groups of subtilases have been identified in sapstaining fungi; however, it
      is not known if these groups have distinct physiological roles (B. Hoffman and C.
      Breuil, Curr. Genet. 41:168-175, 2002). In this work we examined the role of the
      subtilase Albin1 from Ophiostoma piliferum. Reamplification of cDNA ends PCR was
      used to obtain the albin1 gene sequence. The encoded subtilase is probably
      extracellular and involved in nutrient acquisition. This gene was disrupted with
      an Agrobacterium tumefaciens-mediated transformation system. Two of the
      disruptants obtained had significantly lower levels of proteolytic activity,
      slower growth in bovine serum albumin, and significantly reduced growth on wood.
      Thus, albin1 plays an important role in O. piliferum's ability to acquire
      nitrogen from wood proteins.

PMID- 15240262
TI  - Rotavirus virus-like particles as surrogates in environmental persistence and
      inactivation studies.
AB  - Virus-like particles (VLPs) with the full-length VP2 and VP6 rotavirus capsid
      proteins, produced in the baculovirus expression system, have been evaluated as
      surrogates of human rotavirus in different environmental scenarios. Green
      fluorescent protein-labeled VLPs (GFP-VLPs) and particles enclosing a
      heterologous RNA (pseudoviruses), whose stability may be monitored by flow
      cytometry and antigen capture reverse transcription-PCR, respectively, were used.
      After 1 month in seawater at 20 degrees C, no significant differences were
      observed between the behaviors of GFP-VLPs and of infectious rotavirus, whereas
      pseudovirus particles showed a higher decay rate. In the presence of 1 mg of free
      chlorine (FC)/liter both tracers persisted longer in freshwater at 20 degrees C
      than infectious viruses, whereas in the presence of 0.2 mg of FC/liter no
      differences were observed between tracers and infectious rotavirus at short
      contact times. However, from 30 min of contact with FC onward, the decay of
      infectious rotavirus was higher than that of recombinant particles. The predicted
      Ct value for a 90% reduction of GFP-VLPs or pseudoviruses induces a 99.99%
      inactivation of infectious rotavirus. Both tracers were more resistant to UV
      light irradiation than infectious rotavirus in fresh and marine water. The effect
      of UV exposure was more pronounced on pseudovirus than in GFP-VLPs. In all types
      of water, the UV dose to induce a 90% reduction of pseudovirus ensures a 99.99%
      inactivation of infectious rotavirus. Recombinant virus surrogates open new
      possibilities for the systematic validation of virus removal practices in actual
      field situations where pathogenic agents cannot be introduced.

PMID- 15240264
TI  - Lipid accumulation, lipid body formation, and acyl coenzyme A oxidases of the
      yeast Yarrowia lipolytica.
AB  - Yarrowia lipolytica contains five acyl-coenzyme A oxidases (Aox), encoded by the
      POX1 to POX5 genes, that catalyze the limiting step of peroxisomal beta
      oxidation. In this study, we analyzed morphological changes of Y. lipolytica
      growing in an oleic acid medium and the effect of POX deletions on lipid
      accumulation. Protrusions involved in the uptake of lipid droplets (LDs) from the
      medium were seen in electron micrographs of the surfaces of wild-type cells grown
      on oleic acid. The number of protrusions and surface-bound LDs increased during
      growth, but the sizes of the LDs decreased. The sizes of intracellular lipid
      bodies (LBs) and their composition depended on the POX genotype. Only a few,
      small, intracellular LBs were observed in the mutant expressing only Aox4p
      (Deltapox2 Deltapox3 Deltapox5), but strains expressing either Aox3p or both
      Aox3p and Aox4p had the same number of LBs as did the wild type. In contrast,
      strains expressing either Aox2p or both Aox2p and Aox4p formed fewer, but larger,
      LBs than did the wild type. The size of the LBs increased proportionately with
      the amount of triacylglycerols in the LBs of the mutants. In summary, Aox2p
      expression regulates the size of cellular triacylglycerol pools and the size and
      number of LBs in which these fatty acids accumulate.

PMID- 15240263
TI  - Serotypes and virulence gene profiles of shiga toxin-producing Escherichia coli
      strains isolated from feces of pasture-fed and lot-fed sheep.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains possessing genes for
      enterohemolysin (ehxA) and/or intimin (eae), referred to here as complex STEC
      (cSTEC), are more commonly recovered from the feces of humans with hemolytic
      uremic syndrome and hemorrhagic colitis than STEC strains that do not possess
      these accessory virulence genes. Ruminants, particularly cattle and sheep, are
      recognized reservoirs of STEC populations that may contaminate foods destined for
      human consumption. We isolated cSTEC strains from the feces of longitudinally
      sampled pasture-fed sheep, lot-fed sheep maintained on diets comprising various
      combinations of silage and grain, and sheep simultaneously grazing pastures with
      cattle to explore the diversity of cSTEC serotypes capable of colonizing healthy
      sheep. A total of 67 cSTEC serotypes were isolated, of which 21 (31.3%), mainly
      isolated from lambs, have not been reported. Of the total isolations, 58 (86.6%)
      were different from cSTEC serotypes isolated from a recent study of
      longitudinally sampled healthy Australian cattle (M. Hornitzky, B. A. Vanselow,
      K. Walker, K. A. Bettelheim, B. Corney, P. Gill, G. Bailey, and S. P. Djordjevic,
      Appl. Environ. Microbiol. 68:6439-6445, 2002). Our data suggest that cSTEC
      serotypes O5:H(-), O75:H8, O91:H(-), O123:H(-), and O128:H2 are well adapted to
      colonizing the ovine gastrointestinal tract, since they were the most prevalent
      serotypes isolated from both pasture-fed and lot-fed sheep. Collectively, our
      data show that Australian sheep are colonized by diverse cSTEC serotypes that are
      rarely isolated from healthy Australian cattle.

PMID- 15240265
TI  - Analysis and validation of a predictive model for growth and death of Aeromonas
      hydrophila under modified atmospheres at refrigeration temperatures.
AB  - Specific growth and death rates of Aeromonas hydrophila were measured in
      laboratory media under various combinations of temperature, pH, and percent CO(2)
      and O(2) in the atmosphere. Predictive models were developed from the data and
      validated by means of observations obtained from (i) seafood experiments set up
      for this purpose and (ii) the ComBase database (http://www.combase.cc;
      http://wyndmoor.arserrc.gov/combase/). Two main reasons were identified for the
      differences between the predicted and observed growth in food: they were the
      variability of the growth rates in food and the bias of the model predictions
      when applied to food environments. A statistical method is presented to
      quantitatively analyze these differences. The method was also used to extend the
      interpolation region of the model. In this extension, the concept of generalized
      Z values (C. Pin, G. Garcia de Fernando, J. A. Ordonez, and J. Baranyi, Food
      Microbiol. 18:539-545, 2001) played an important role. The extension depended
      partly on the density of the model-generating observations and partly on the
      accuracy of extrapolated predictions close to the boundary of the interpolation
      region. The boundary of the growth region of the organism was also estimated by
      means of experimental results for growth and death rates.

PMID- 15240266
TI  - Properties of a novel thermostable glucoamylase from the hyperthermophilic
      archaeon Sulfolobus solfataricus in relation to starch processing.
AB  - A gene (ssg) encoding a putative glucoamylase in a hyperthermophilic archaeon,
      Sulfolobus solfataricus, was cloned and expressed in Escherichia coli, and the
      properties of the recombinant protein were examined in relation to the glucose
      production process. The recombinant glucoamylase was extremely thermostable, with
      an optimal temperature at 90 degrees C. The enzyme was most active in the pH
      range from 5.5 to 6.0. The enzyme liberated beta-d-glucose from the substrate
      maltotriose, and the substrate preference for maltotriose distinguished this
      enzyme from fungal glucoamylases. Gel permeation chromatography and sedimentation
      equilibrium analytical ultracentrifugation analysis revealed that the enzyme
      exists as a tetramer. The reverse reaction of the glucoamylase from S.
      solfataricus produced significantly less isomaltose than did that of industrial
      fungal glucoamylase. The glucoamylase from S. solfataricus has excellent
      potential for improving industrial starch processing by eliminating the need to
      adjust both pH and temperature.

PMID- 15240267
TI  - Biodegradation of all stereoisomers of the EDTA substitute iminodisuccinate by
      Agrobacterium tumefaciens BY6 requires an epimerase and a stereoselective C-N
      lyase.
AB  - Biodegradation tests according to Organization for Economic Cooperation and
      Development standard 301F (manometric respirometry test) with technical
      iminodisuccinate (IDS) revealed ready biodegradability for all stereoisomers of
      IDS. The IDS-degrading strain Agrobacterium tumefaciens BY6 was isolated from
      activated sludge. The strain was able to grow on each IDS isomer as well as on
      Fe(2+)-, Mg(2+)-, and Ca(2+)-IDS complexes as the sole carbon, nitrogen, and
      energy source. In contrast, biodegradation of and growth on Mn(2+)-IDS were
      rather scant and very slow on Cu(2+)-IDS. Growth and turnover experiments with A.
      tumefaciens BY6 indicated that the isomer R,S-IDS is the preferred substrate. The
      IDS-degrading enzyme system isolated from this organism consists of an IDS
      epimerase and a C-N lyase. The C-N lyase is stereospecific for the cleavage of
      R,S-IDS, generating d-aspartic acid and fumaric acid. The decisive enzyme for S,S
      IDS and R,R-IDS degradation is the epimerase. It transforms S,S-IDS and R,R-IDS
      into R,S-IDS. Both enzymes do not require any cofactors. The two enzymes were
      purified and characterized, and the N-termini were sequenced. The purified lyase
      and also the epimerase catalyzed the transformation of alkaline earth metal-IDS
      complexes, while heavy metal-IDS complexes were transformed rather slowly or not
      at all. The observed mechanism for the complete mineralization of all IDS isomers
      involving an epimerase offers an interesting possibility of funneling all
      stereoisomers into a catabolic pathway initiated by a stereoselective lyase.

PMID- 15240268
TI  - Temporal and spatial profiles of chitinase expression by norway spruce in
      response to bark colonization by Heterobasidion annosum.
AB  - Pathogen colonization and transcript levels of three host chitinases, putatively
      representing classes I, II, and IV, were monitored with real-time PCR after
      wounding and bark infection by Heterobasidion annosum in 32-year-old trees of
      Norway spruce (Picea abies) with low (clone 409) or high (clone 589) resistance
      to this pathogen. Three days after inoculation, comparable colonization levels
      were observed in both clones in the area immediately adjacent to inoculation. At
      14 days after infection, pathogen colonization was restricted to the area
      immediately adjacent to the site of inoculation for clone 589 but had progressed
      further into the host tissue in clone 409. Transcript levels of the class II and
      IV chitinases increased after wounding or inoculation, but the transcript level
      of the class I chitinase declined after these treatments. Transcript levels of
      the class II and class IV chitinases were higher in areas immediately adjacent to
      the inoculation site in clone 589 than in similar sites in clone 409 3 days after
      inoculation. This difference was even more pronounced 2 to 6 mm away from the
      inoculation point, where no infection was yet established, and suggests that the
      clones differ in the rate of chitinase-related signal perception or transduction.
      At 14 days after inoculation, these transcript levels were higher in clone 409
      than in clone 589, suggesting that the massive upregulation of class II and IV
      chitinases after the establishment of infection comes too late to reduce or
      prevent pathogen colonization.

PMID- 15240269
TI  - A new black Aspergillus species, A. vadensis, is a promising host for homologous
      and heterologous protein production.
AB  - A new species of the group of black aspergilli, Aspergillus vadensis, was
      analyzed for its potential as a host for homologous and heterologous protein
      production. Unlike the other black aspergilli, this strain does not acidify the
      culture medium when nitrate is the nitrogen source and only produces very low
      levels of extracellular proteases, mainly serine metalloproteases. The stability
      of A. tubingensis feruloyl esterase A (FaeA) was compared upon production in wild
      type A. vadensis, A. tubingensis, and an A. niger strain in which the three main
      protease-encoding genes were disrupted. The production of FaeA in A. vadensis
      resulted in larger amounts of intact protein than production in A. tubingensis
      and was similar to production in an A. niger protease disruptant, confirming in
      vivo the low proteolytic activity of A. vadensis. The protoplast formation and
      transformation efficiencies of A. vadensis were much higher than those of A.
      niger. These characteristics make A. vadensis a very promising candidate for
      homologous, and possibly heterologous, protein production.

PMID- 15240270
TI  - Disruption of a gene predicted to encode a solute binding protein of an ABC
      transporter reduces transmission of Spiroplasma citri by the leafhopper
      Circulifer haematoceps.
AB  - Spiroplasma citri is transmitted from plant to plant by phloem-feeding
      leafhoppers. In an attempt to identify mechanisms involved in transmission,
      mutants of S. citri affected in their transmission must be available. For this
      purpose, transposon (Tn4001) mutagenesis was used to produce mutants which have
      been screened for their ability to be transmitted by the leafhopper vector
      Circulifer haematoceps to periwinkle plants. With one mutant (G76) which
      multiplied in leafhoppers as efficiently as S. citri wild-type (wt) strain GII-3,
      the plants showed symptoms 4 to 5 weeks later than those infected with wt GII-3.
      Thirty to fifty percent of plants exposed to leafhoppers injected with G76
      remained symptomless, whereas for wt GII-3, all plants exposed to the
      transmission showed severe symptoms. This suggests that the mutant G76 was
      injected into plants by the leafhoppers less efficiently than wt GII-3. To check
      this possibility, the number of spiroplasma cells injected by a leafhopper
      through a Parafilm membrane into SP4 medium was determined. Thirty times less
      mutant G76 than wt GII-3 was transmitted through the membrane. These results
      suggest that mutant G76 was affected either in its capacity to penetrate the
      salivary glands and/or to multiply within them. In mutant G76, transposon Tn4001
      was shown to be inserted into a gene encoding a putative lipoprotein (Sc76) In
      the ABCdb database Sc76 protein was noted as a solute binding protein of an ABC
      transporter of the family S1_b. Functional complementation of the G76 mutant with
      the Sc76 gene restored the wild phenotype, showing that Sc76 protein is involved
      in S. citri transmission by the leafhopper vector C. haematoceps.

PMID- 15240271
TI  - Relationship between gyrA mutations and quinolone resistance in Flavobacterium
      psychrophilum isolates.
AB  - Flavobacterium psychrophilum is the causative agent of the fish diseases called
      bacterial cold-water disease and rainbow trout fry syndrome. It has been reported
      that some isolates of F. psychrophilum are resistant to quinolones; however, the
      mechanism of this quinolone resistance has been unexplained. In this study, we
      examined the quinolone susceptibility patterns of 27 F. psychrophilum strains
      isolated in Japan and the United States. Out of 27 isolates, 14 were resistant to
      both nalidixic acid (NA) and oxolinic acid (OXA), and the others were susceptible
      to NA and OXA. When amino acid sequences deduced from gyrA nucleotide sequences
      of all isolates tested were analyzed, two amino acid substitutions (a threonine
      residue replaced by an alanine or isoleucine residue in position 83 of GyrA
      [Escherichia coli numbering] and an aspartic acid residue replaced by a tyrosine
      residue in position 87) were observed in the 14 quinolone-resistant isolates.
      These results strongly suggest that, as in other gram-negative bacteria, DNA
      gyrase is an important target for quinolones in F. psychrophilum.

PMID- 15240272
TI  - Genetic characterization and transmission cycles of Cryptosporidium species
      isolated from humans in New Zealand.
AB  - Little is known about the genetic characteristics, distribution, and transmission
      cycles of Cryptosporidium species that cause human disease in New Zealand. To
      address these questions, 423 fecal specimens containing Cryptosporidium oocysts
      and obtained from different regions were examined by the PCR-restriction fragment
      length polymorphism technique. Indeterminant results were resolved by DNA
      sequence analysis. Two regions supplied the majority of isolates: one rural and
      one urban. Overall, Cryptosporidium hominis accounted for 47% of the isolates,
      with the remaining 53% being the C. parvum bovine genotype. A difference,
      however, was observed between the Cryptosporidium species from rural and urban
      isolates, with C. hominis dominant in the urban region, whereas the C. parvum
      bovine genotype was prevalent in rural New Zealand. A shift in transmission
      cycles was detected between seasons, with an anthroponotic cycle in autumn and a
      zoonotic cycle in spring. A novel Cryptosporidium sp., which on DNA sequence
      analysis showed a close relationship with C. canis, was detected in two unrelated
      children from different regions, illustrating the genetic diversity within this
      genus.

PMID- 15240273
TI  - Toxic and nontoxic microcystis colonies in natural populations can be
      differentiated on the basis of rRNA gene internal transcribed spacer diversity.
AB  - Assessing and predicting bloom dynamics and toxin production by Microcystis
      requires analysis of toxic and nontoxic Microcystis genotypes in natural
      communities. We show that genetic differentiation of Microcystis colonies based
      on rRNA internal transcribed spacer (ITS) sequences provides an adequate basis
      for recognition of microcystin producers. Consequently, ecological studies of
      toxic and nontoxic cyanobacteria are now possible through studies of rRNA ITS
      genotypic diversity in isolated cultures or colonies and in natural communities.
      A total of 107 Microcystis colonies were isolated from 15 lakes in Europe and
      Morocco, the presence of microcystins in each colony was examined by matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS), and they were grouped by rRNA ITS denaturing gradient gel electrophoresis
      (DGGE) typing. Based on DGGE analysis of amplified ITSa and ITSc fragments,
      yielding supplementary resolution (I. Janse et al., Appl. Environ. Microbiol.
      69:6634-6643, 2003), the colonies could be differentiated into 59 classes.
      Microcystin-producing and non-microcystin-producing colonies ended up in
      different classes. Sequences from the rRNA ITS of representative strains were
      congruent with the classification based on DGGE and confirmed the recognition of
      microcystin producers on the basis of rRNA ITS. The rRNA ITS sequences also
      confirmed inconsistencies reported for Microcystis identification based on
      morphology. There was no indication for geographical restriction of strains,
      since identical sequences originated from geographically distant lakes. About 28%
      of the analyzed colonies gave rise to multiple bands in DGGE profiles, indicating
      either aggregation of different colonies, or the occurrence of sequence
      differences between multiple operons. Cyanobacterial community profiles from two
      Dutch lakes from which colonies had been isolated showed different relative
      abundances of genotypes between bloom stages and between the water column and
      surface scum. Although not all bands in the community profiles could be matched
      with isolated colonies, the profiles suggest a dominance of nontoxic colonies,
      mainly later in the season and in scums.

PMID- 15240274
TI  - Abundance of dioxygenase genes similar to Ralstonia sp. strain U2 nagAc is
      correlated with naphthalene concentrations in coal tar-contaminated freshwater
      sediments.
AB  - We designed a real-time PCR assay able to recognize dioxygenase large-subunit
      gene sequences with more than 90% similarity to the Ralstonia sp. strain U2 nagAc
      gene (nagAc-like gene sequences) in order to study the importance of organisms
      carrying these genes in the biodegradation of naphthalene. Sequencing of PCR
      products indicated that this real-time PCR assay was specific and able to detect
      a variety of nagAc-like gene sequences. One to 100 ng of contaminated-sediment
      total DNA in 25-microl reaction mixtures produced an amplification efficiency of
      0.97 without evident PCR inhibition. The assay was applied to surficial
      freshwater sediment samples obtained in or in close proximity to a coal tar
      contaminated Superfund site. Naphthalene concentrations in the analyzed samples
      varied between 0.18 and 106 mg/kg of dry weight sediment. The assay for nagAc
      like sequences indicated the presence of (4.1 +/- 0.7) x 10(3) to (2.9 +/- 0.3) x
      10(5) copies of nagAc-like dioxygenase genes per microg of DNA extracted from
      sediment samples. These values corresponded to (1.2 +/- 0.6) x 10(5) to (5.4 +/-
      0.4) x 10(7) copies of this target per g of dry weight sediment when losses of
      DNA during extraction were taken into account. There was a positive correlation
      between naphthalene concentrations and nagAc-like gene copies per microgram of
      DNA (r = 0.89) and per gram of dry weight sediment (r = 0.77). These results
      provide evidence of the ecological significance of organisms carrying nagAc-like
      genes in the biodegradation of naphthalene.

PMID- 15240275
TI  - Control of Listeria monocytogenes in a biofilm by competitive-exclusion
      microorganisms.
AB  - Biofilms from drains in food processing facilities with a recent history of no
      detectable Listeria monocytogenes in floor drains were cultured for
      microorganisms producing antilisterial metabolites. A total of 413 microbial
      isolates were obtained from 12 drain biofilm samples and were assayed at 15 and
      37 degrees C for activities that were bactericidal or inhibitory to L.
      monocytogenes, by two agar plate assays. Twenty-one of 257 bacterial isolates and
      3 of 156 yeast isolates had antilisterial activity. All 24 isolates which
      produced metabolites inhibitory to L. monocytogenes were assayed for
      antilisterial activity in coinoculated broth cultures containing tryptic soy
      broth with yeast extract (TSB-YE). A five-strain mixture of 10(3) CFU of L.
      monocytogenes/ml and 10(5) CFU of the candidate competitive-exclusion
      microorganism/ml was combined in TSB-YE and incubated at 37 degrees C for 24 h,
      15 degrees C for 14 days, 8 degrees C for 21 days, and 4 degrees C for 28 days.
      Substantial inhibition of L. monocytogenes growth (4 to 5 log CFU/ml) was
      observed for nine bacterial isolates at 37 degrees C, two at 15 and 8 degrees C,
      and three at 4 degrees C. The inhibitory isolates were identified as Enterococcus
      durans (six isolates), Lactococcus lactis subsp. lactis (two isolates), and
      Lactobacillus plantarum (one isolate). The anti-L. monocytogenes activity of
      these isolates was evaluated in biofilms of L. monocytogenes on stainless steel
      coupons at 37, 15, 8, and 4 degrees C. Results revealed that two isolates (E.
      durans strain 152 and L. lactis subsp. lactis strain C-1-92) were highly
      inhibitory to L. monocytogenes (growth inhibition of >5 log(10) CFU of L.
      monocytogenes/cm(2)). These two bacterial isolates appear to be excellent
      competitive-exclusion candidates to control L. monocytogenes in biofilms at
      environmental temperatures of 4 to 37 degrees C.

PMID- 15240276
TI  - Effect of pyocyanin on a crude-oil-degrading microbial community.
AB  - Pseudomonas aeruginosa is an n-alkane degrader that is frequently isolated from
      petroleum-contaminated sites and produces factors that enhance its
      competitiveness and survival in many environments. In this study, one such
      factor, pyocyanin, has been detected in an oil-degrading culture containing P.
      aeruginosa and is a redox-active compound capable of inhibiting microbial growth.
      To examine the effects of pyocyanin further, an oil-degrading culture was grown
      with and without 9.5 microM pyocyanin and microbial community structure and oil
      degradation were monitored for 50 days. Denaturing gradient gel electrophoresis
      (DGGE) analysis of cultures revealed a decrease in the microbial community
      diversity in the pyocyanin-amended cultures compared to that of the unamended
      cultures. Two members of the microbial community in pure culture exhibited
      intermediate and high sensitivities to pyocyanin corresponding to intermediate
      and low levels of activity for the antioxidant enzymes catalase and superoxide
      dismutase, respectively. Another member of the community that remained constant
      in the DGGE gels over the 50-day culture incubation period exhibited no
      sensitivity to pyocyanin, corresponding to a high level of catalase and
      superoxide dismutase when examined in pure culture. Pyocyanin also affected the
      overall degradation of the crude oil. At 50 days, the culture without pyocyanin
      had decreased polycyclic aromatic hydrocarbons compared to the pyocyanin-amended
      culture, with a specific reduction in the degradation of dibenzothiophenes,
      naphthalenes, and C(29) and C(30) hopanes. This study demonstrated that pyocyanin
      influenced the diversity of the microbial community and suggests the importance
      of understanding how interspecies interactions influence the degradation
      capability of a microbial community.

PMID- 15240277
TI  - Multivariate analyses of Burkholderia species in soil: effect of crop and land
      use history.
AB  - The assessment of Burkholderia diversity in agricultural areas is important
      considering the potential use of this genus for agronomic and environmental
      applications. Therefore, the aim of this work was to ascertain how plant species
      and land use management drive the diversity of the genus Burkholderia. In a
      greenhouse experiment, different crops, i.e., maize, oat, barley, and grass, were
      planted in pots containing soils with different land use histories, i.e., maize
      monoculture, crop rotation, and permanent grassland, for three consecutive growth
      cycles. The diversity of Burkholderia spp. in the rhizosphere soil was assessed
      by genus-specific PCR-denaturing gradient gel electrophoresis (DGGE) and analyzed
      by canonical correspondence analysis (CCA). CCA ordination plots showed that
      previous land use was the main factor affecting the composition of the
      Burkholderia community. Although most variation in the Burkholderia community
      structure was observed between the permanent grassland and agricultural areas,
      differences between the crop rotation and maize monoculture groups were also
      observed. Plant species affected Burkholderia community structure to a lesser
      extent than did land use history. Similarities were observed between Burkholderia
      populations associated with maize and grass, on the one hand, and between those
      associated with barley and oat, on the other hand. Additionally, CCA ordination
      plots demonstrated that these two groups (maize/grass versus barley/oat) had a
      negative correlation. The identification of bands from the DGGE patterns
      demonstrated that the species correlated with the environmental variables were
      mainly affiliated with Burkholderia species that are commonly isolated from soil,
      in particular Burkholderia glathei, B. caledonica, B. hospita, and B.
      caribiensis.

PMID- 15240278
TI  - Effect of high-pressure-induced ice I-to-ice III phase transitions on
      inactivation of Listeria innocua in frozen suspension.
AB  - The inactivation of Listeria innocua BGA 3532 at subzero temperatures and
      pressures up to 400 MPa in buffer solution was studied to examine the impact of
      high-pressure treatments on bacteria in frozen matrices. The state of aggregation
      of water was taken into account. The inactivation was progressing rapidly during
      pressure holding under liquid conditions, whereas in the ice phases, extended
      pressure holding times had comparatively little effect. The transient phase
      change of ice I to other ice polymorphs (ice II or ice III) during pressure
      cycles above 200 MPa resulted in an inactivation of about 3 log cycles, probably
      due to the mechanical stress associated with the phase transition. This effect
      was independent of the applied pressure holding time. Flow cytometric analyses
      supported the assumption of different mechanisms of inactivation of L. innocua in
      the liquid phase and ice I (large fraction of sublethally damaged cells due to
      pressure inactivation) in contrast to cells subjected to ice I-to-ice III phase
      transitions (complete inactivation due to cell rupture). Possible applications of
      high-pressure-induced phase transitions include cell disintegration for the
      recovery of intracellular components and inactivation of microorganisms in frozen
      food.

PMID- 15240279
TI  - Characterization of Salmonella enterica serovar typhimurium from marine
      environments in coastal waters of Galicia (Spain).
AB  - Twenty-three Salmonella enterica serovar Typhimurium isolates from marine
      environments were characterized by phage typing, pulsed-field gel electrophoresis
      (PFGE) analysis, plasmid analysis, and antibiotic resistance, and the
      distribution of the different types in the coastal waters were subsequently
      analyzed. Five phage types were identified among the isolates (PT41, PT135, PT99,
      DT104, and DT193). PT135 isolates were exclusively detected during the winter
      months from 1998 to 2000, whereas DT104 and PT41 isolates were detected
      exclusively in the summer months from 2000 to 2002. XbaI PFGE analysis revealed 9
      PFGE types, and plasmid profiling identified 8 plasmid types (with 1 to 6
      plasmids) among the isolates. Only three isolates presented multidrug resistance
      to antibiotics. Two DT104 isolates were resistant to 8 and 7 antibiotics
      (profiles ACCeFNaSSuT and ACeFNeSSuT), whereas a PT193 isolate presented
      resistance to 6 antibiotics (profile ACFSSu). In addition, four PT41 isolates
      were resistant to a single antibiotic. The detection of multidrug-resistant phage
      types DT104 and DT193 in shellfish emphasizes the importance of monitoring the
      presence of Salmonella in routine surveillance of live bivalve molluscs.

PMID- 15240280
TI  - Evaluation of a strategy for Toxoplasma gondii oocyst detection in water.
AB  - Several recent outbreaks of toxoplasmosis were related to drinking water. We
      propose a strategy for Toxoplasma oocyst detection as part of an approach to
      detecting multiple waterborne parasites, including Giardia and Cryptosporidium
      spp., by the U.S. Environmental Protection Agency method with the same sample.
      Water samples are filtered to recover Toxoplasma oocysts and purified on a
      sucrose density gradient. Detection is based on PCR and mouse inoculation
      (bioassay) to determine the presence and infectivity of recovered oocysts. In an
      experimental seeding assay with 100 liters of deionized water, a parasite density
      of 1 oocyst/liter was successfully detected by PCR in 60% of cases and a density
      of 10 oocysts/liter was detected in 100% of cases. The sensitivity of the PCR
      assay varied from less than 10 to more than 1000 oocysts/liter, depending on the
      sample source. PCR was always more sensitive than mouse inoculation. This
      detection strategy was then applied to 139 environmental water samples collected
      over a 20-month period. Fifty-three samples contained PCR inhibitors, which were
      overcome in 39 cases by bovine serum albumin addition. Among 125 interpretable
      samples, we detected Toxoplasma DNA in 10 cases (8%). None of the samples were
      positive by mouse inoculation. This strategy efficiently detects Toxoplasma
      oocysts in water and may be suitable as a public health sentinel method.

PMID- 15240281
TI  - Initial reaction(s) in biotransformation of CL-20 is catalyzed by salicylate 1
      monooxygenase from Pseudomonas sp. strain ATCC 29352.
AB  - CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)
      (C(6)H(6)N(12)O(12)), a future-generation high-energy explosive, is biodegradable
      by Pseudomonas sp. strain FA1 and Agrobacterium sp. strain JS71; however, the
      nature of the enzyme(s) involved in the process was not understood. In the
      present study, salicylate 1-monooxygenase, a flavin adenine dinucleotide (FAD)
      containing purified enzyme from Pseudomonas sp. strain ATCC 29352, biotransformed
      CL-20 at rates of 0.256 +/- 0.011 and 0.043 +/- 0.003 nmol min(-1) mg of protein(
      1) under anaerobic and aerobic conditions, respectively. The disappearance of CL
      20 was accompanied by the release of nitrite ions. Using liquid
      chromatography/mass spectrometry in the negative electrospray ionization mode, we
      detected a metabolite with a deprotonated mass ion [M - H](-) at 345 Da,
      corresponding to an empirical formula of C(6)H(6)N(10)O(8), produced as a result
      of two sequential N denitration steps on the CL- 20 molecule. We also detected
      two isomeric metabolites with [M - H](-) at 381 Da corresponding to an empirical
      formula of C(6)H(10)N(10)O(10). The latter was a hydrated product of the
      metabolite C(6)H(6)N(10)O(8) with addition of two H(2)O molecules, as confirmed
      by tests using (18)O-labeled water. The product stoichiometry showed that each
      reacted CL-20 molecule produced about 1.7 nitrite ions, 3.2 molecules of nitrous
      oxide, 1.5 molecules of formic acid, and 0.6 ammonium ion. Diphenyliodonium
      mediated inhibition of salicylate 1-monooxygenase and a comparative study between
      native, deflavo, and reconstituted enzyme(s) showed that FAD site of the enzyme
      was involved in the biotransformation of CL-20 catalyzed by salicylate 1
      monooxygenase. The data suggested that salicylate 1-monooxygenase catalyzed two
      oxygen-sensitive single-electron transfer steps necessary to release two nitrite
      ions from CL-20 and that this was followed by the secondary decomposition of this
      energetic chemical.

PMID- 15240282
TI  - Effect of dilution rate on metabolic pathway shift between aceticlastic and
      nonaceticlastic methanogenesis in chemostat cultivation.
AB  - Acetate conversion pathways of methanogenic consortia in acetate-fed chemostats
      at dilution rates of 0.025 and 0.6 day(-1) were investigated by using (13)C
      labeled acetates, followed by gas chromatography-mass spectrometry (GC-MS)
      analysis of the CH(4) and CO(2) produced. Nonaceticlastic syntrophic oxidation by
      acetate-oxidizing syntrophs and hydrogenotrophic methanogens was suggested to
      occupy a primary pathway (approximately 62 to 90%) in total methanogenesis at the
      low dilution rate. In contrast, aceticlastic cleavage of acetate by aceticlastic
      methanogens was suggested to occupy a primary pathway (approximately 95 to 99%)
      in total methanogenesis at the high dilution rate. Phylogenetic analyses of
      transcripts of the methyl coenzyme M reductase gene (mcrA) confirmed that a
      significant number of transcripts of the genera Methanoculleus (hydrogenotrophic
      methanogens) and Methanosarcina (aceticlastic methanogens) were present in the
      chemostats at the low and high dilution rates, respectively. The mcrA transcripts
      of the genus Methanosaeta (aceticlastic methanogens), which dominated the
      population in a previous study (T. Shigematsu, Y. Tang, H. Kawaguchi, K.
      Ninomiya, J. Kijima, T. Kobayashi, S. Morimura, and K. Kida, J. Biosci. Bioeng.
      96:547-558, 2003), were poorly detected at both dilution rates due to the limited
      coverage of the primers used. These results demonstrated that the dilution rate
      could cause a shift in the primary pathway of acetate conversion to methane in
      acetate-fed chemostats.

PMID- 15240283
TI  - Mineralization of individual congeners of linear alkylbenzenesulfonate by defined
      pairs of heterotrophic bacteria.
AB  - Parvibaculum lavamentivorans DS-1(T) utilized the commercial surfactant linear
      alkylbenzenesulfonate (LAS) (20 congeners with C(10) to C(13) side chains) as a
      carbon and energy source by shortening the side chain, and
      sulfophenylcarboxylates (SPCs) and similar compounds (e.g., alpha,beta
      unsaturated SPCs [SPC-2Hs]) were excreted with quantitative recovery of the
      sulfophenyl moiety. 2-(4-Sulfophenyl)decane (2-C10-LAS) was converted largely to
      3-(4-sulfophenyl)butyrate (3-C4-SPC), as were 2-C12-LAS and 2-C14-LAS; the other
      products were 5-C6-SPC (SPC+2C) and 3-C4-SPC-2H. 2-C11-LAS was converted largely
      to 4-C5-SPC with the corresponding SPC+2C and SPC-2H; similarly, 3-C12-LAS
      yielded 4-C6-SPC with the corresponding SPC+2C and SPC-2H. This pattern of
      products confirmed that LAS is degraded by omega-oxygenation and chain shortening
      through beta-oxidation. At least nine major SPCs were formed from commercial LAS.
      The novel isolates Comamonas testosteroni SPB-2 and KF-1 utilized 3-C4-SPC;
      Delftia acidovorans SPH-1 utilized 4-C6-SPC enantioselectively. The substrate
      dependent oxygen uptake of whole cells of strain SPB-2 indicated that there was
      inducible oxygenation of 3-C4-SPC and of 4-sulfophenol in whole cells of the
      strains of C. testosteroni during growth with 3-C4-SPC or 4-sulfophenol. The
      degradative pathways apparently involved 4-sulfocatechol and 4-sulfocatechol 1,2
      dioxygenase. Strain SPB-2 and strain DS-1(T) grew together in LAS-salts medium,
      and only seven of the nine major SPCs were recovered. Strain SPB-2 utilized 3-C4
      SPC, 3-C5-SPC, and 3-C4-SPC-2H. Strain SPH-1 grew together with strain DS-1(T) in
      LAS-salts medium, and a different set of seven major SPCs was recovered. Strain
      SPH-1 utilized 4-C6-SPC, 4-C5-SPC, 4-C6-SPC-2H, and 4-C5-SPC-2H. A three-member
      community consisting of strains DS-1(T), SPB-2, and SPH-1 utilized four major
      SPCs. We inferred that this community mineralized the major SPCs derived from 8
      of the 20 LAS congeners.

PMID- 15240284
TI  - A single species, Micromonas pusilla (Prasinophyceae), dominates the eukaryotic
      picoplankton in the Western English Channel.
AB  - The class Prasinophyceae (Chlorophyta) contains several photosynthetic
      picoeukaryotic species described from cultured isolates. The ecology of these
      organisms and their contributions to the picoeukaryotic community in aquatic
      ecosystems have received little consideration. We have designed and tested eight
      new 18S ribosomal DNA oligonucleotide probes specific for different
      Prasinophyceae clades, genera, and species. Using fluorescent in situ
      hybridization associated with tyramide signal amplification, these probes, along
      with more general probes, have been applied to samples from a marine coastal site
      off Roscoff (France) collected every 2 weeks between July 2000 and September
      2001. The abundance of eukaryotic picoplankton remained high (>10(3) cells ml(
      1)) during the sampling period, with maxima in summer (up to 2 x 10(4) cells ml(
      1)), and a single green algal species, Micromonas pusilla (Prasinophyceae),
      dominated the community all year round. Members of the order Prasinococcales and
      the species Bathycoccus prasinos (Mamiellales) displayed sporadic occurrences,
      while the abundances of all other Prasinophyceae groups targeted remained
      negligible.

PMID- 15240285
TI  - Structural characterization of lignin during Pinus taeda wood treatment with
      Ceriporiopsis subvermispora.
AB  - Pinus taeda wood chips were biotreated with Ceriporiopsis subvermispora under
      solid-state fermentation for periods varying from 15 to 90 days. Milled wood
      lignins extracted from sound and biotreated wood samples were characterized by
      wet-chemical and spectroscopic techniques. Treatment of the lignins by
      derivatization followed by reductive cleavage (DFRC) made it possible to detect
      DFRC monomers and dimers that are diagnostic of the occurrence of arylglycerol
      beta-O-aryl and beta-beta, beta-5, beta-1, and 4-O-5 units in the lignin
      structure. Quantification of these DFRC products indicated that beta-O-aryl
      cleavage was a significant route for lignin biodegradation but that beta-beta,
      beta-5, beta-1, and 4-O-5 linkages were more resistant to the biological attack.
      The amount of aromatic hydroxyls did not increase with the split of beta-O-4
      linkages, suggesting that the beta-O-4 cleavage products remain as quinone-type
      structures as detected by UV and visible spectroscopy. Nuclear magnetic resonance
      techniques also indicated the formation of new substructures containing
      nonoxygenated, saturated aliphatic carbons (CH(2) and CH(3)) in the side chains
      of lignins extracted from biotreated wood samples.

PMID- 15240286
TI  - Light dependence of [3H]leucine incorporation in the oligotrophic North Pacific
      ocean.
AB  - The influence of irradiance on bacterial incorporation of [(3)H]leucine was
      evaluated at Station ALOHA in the oligotrophic North Pacific subtropical gyre.
      Six experiments were conducted on three cruises to Station ALOHA to examine how
      [(3)H]leucine incorporation varied as a function of irradiance. Two experiments
      were also conducted to assess the photoautotrophic response to irradiance (based
      on photosynthetic uptake of [(14)C]bicarbonate) in both the upper and lower
      photic zones. Rates of [(3)H]leucine incorporation responded to irradiance in a
      photosynthesis-like manner, increasing sharply at low light and then saturating
      and sometimes declining with increasing light intensity. The influence of
      irradiance on bacterial growth was evaluated in both the well-lit (5 to 25 m) and
      dimly lit regions of the upper ocean (75 to 100 m) to determine whether the
      bacterial response to irradiance differed along the depth-dependent light
      gradient of the photic zone. [(3)H]leucine incorporation rates were analyzed with
      a photosynthesis-irradiance model for a quantitative description of the
      relationships between [(3)H]leucine incorporation and irradiance. Maximum rates
      of [(3)H]leucine incorporation in the upper photic zone increased 48 to 92%
      relative to those of dark-incubated samples, with [(3)H]leucine incorporation
      saturating at light intensities between 58 and 363 micromol of quanta m(-2) s(
      1). Rates of [(3)H]leucine incorporation in the deep photic zone were
      photostimulated 53 to 114% and were susceptible to photoinhibition, with rates
      declining at light intensities of >100 micromol of quanta m(-2) s(-1). The
      results of these experiments revealed that sunlight directly influences bacterial
      growth in this open-ocean ecosystem.

PMID- 15240287
TI  - Populations implicated in anaerobic reductive dechlorination of 1,2
      dichloropropane in highly enriched bacterial communities.
AB  - 1,2-Dichloropropane (1,2-D), a widespread groundwater contaminant, can be
      reductively dechlorinated to propene by anaerobic bacteria. To shed light on the
      populations involved in the detoxification process, a comprehensive 16S rRNA gene
      based bacterial community analysis of two enrichment cultures derived from
      geographically distinct locations was performed. Analysis of terminal restriction
      fragments, amplicons obtained with dechlorinator-specific PCR primers, and
      enumeration with quantitative real-time PCR as well as screening clone libraries
      all implied that Dehalococcoides populations were involved in 1,2-D
      dechlorination in both enrichment cultures. Physiological traits (e.g.,
      dechlorination in the presence of ampicillin and a requirement for hydrogen as
      the electron donor) supported the involvement of Dehalococcoides populations in
      the dechlorination process. These findings expand the spectrum of chloroorganic
      compounds used by Dehalococcoides species as growth-supporting electron
      acceptors. The combined molecular approach allowed a comparison between different
      16S rRNA gene-based approaches for the detection of Dehalococcoides populations.

PMID- 15240288
TI  - Replication of the endosymbiotic bacterium Blochmannia floridanus is correlated
      with the developmental and reproductive stages of its ant host.
AB  - The dynamics of replication of the intracellular endosymbiotic bacterium
      Blochmannia floridanus was determined during the larval development of its host
      ant Camponotus floridanus by real-time quantitative PCR. The bacteria were found
      to proliferate during pupation and immediately after the eclosion of the imagines
      (adult ants). In older workers the number of bacteria present in the midgut
      bacteriocytes decreased significantly. In contrast, the bacterial population in
      the ovaries was dependent on the reproductive state of the animal. An age
      dependent degeneration of the midgut bacteriocytes was also investigated by
      microscopic techniques in males and female castes of the closely related ant
      species C. herculeanus and C. sericeiventris, respectively, with similar results
      and supports the concept of age-dependent degeneration of the midgut
      bacteriocytes in all castes.

PMID- 15240290
TI  - CO2- and anaerobiosis-induced changes in physiology and gene expression of
      different Listeria monocytogenes strains.
AB  - Although carbon dioxide (CO(2)) is known to inhibit growth of most bacteria, very
      little is known about the cellular response. The food-borne pathogen Listeria
      monocytogenes is characterized by its ability to grow in high CO(2)
      concentrations at refrigeration temperatures. We examined the listerial responses
      of different strains to growth in air, 100% N(2), and 100% CO(2). The CO(2)
      induced changes in membrane lipid fatty acid composition and expression of
      selected genes were strain dependent. The acid-tolerant L. monocytogenes LO28
      responded in the same manner to CO(2) as to other anaerobic, slightly acidic
      environments (100% N(2), pH 5.7). An increase in the expression of the genes
      encoding glutamate decarboxylase (essential for survival in strong acid) as well
      as an increased amount of branched-chain fatty acids in the membrane was observed
      in both atmospheres. In contrast, the acid-sensitive L. monocytogenes strain EGD
      responded differently to CO(2) and N(2) at the same pH. In a separate experiment
      with L. monocytogenes 412, an increased isocitrate dehydrogenase activity level
      was observed for cells grown in CO(2)-containing atmospheres. Together, our
      findings demonstrate that the CO(2)-response is a partly strain-dependent complex
      mechanism. The possible links between the CO(2)-dependent changes in isocitrate
      dehydrogenase activity, glutamate metabolism and branched fatty acid biosynthesis
      are discussed.

PMID- 15240289
TI  - Diversity and dynamics of a north atlantic coastal Vibrio community.
AB  - Vibrios are ubiquitous marine bacteria that have long served as models for
      heterotrophic processes and have received renewed attention because of the
      discovery of increasing numbers of facultatively pathogenic strains. Because the
      occurrence of specific vibrios has frequently been linked to the temperature,
      salinity, and nutrient status of water, we hypothesized that seasonal changes in
      coastal water bodies lead to distinct vibrio communities and sought to
      characterize their level of differentiation. A novel technique was used to
      quantify shifts in 16S rRNA gene abundance in samples from Barnegat Bay, N.J.,
      collected over a 15-month period. Quantitative PCR (QPCR) with primers specific
      for the genus Vibrio was combined with separation and quantification of amplicons
      by constant denaturant capillary electrophoresis (CDCE). Vibrio populations
      identified by QPCR-CDCE varied between summer and winter samples, suggesting
      distinct warm-water and year-round populations. Identification of the CDCE
      populations by cloning and sequencing of 16S rRNA genes from two summer and two
      winter samples confirmed this distinction. It further showed that CDCE
      populations corresponded in most cases to approximately 98% rRNA similarity
      groups and suggested that the abundance of these follows temperature trends.
      Phylogenetic comparison yielded closely related cultured and often pathogenic
      representatives for most sequences, and the temperature ranges of these isolates
      confirmed the trends seen in the environmental samples. Overall, this suggests
      that temperature is a good predictor of the occurrence of closely related vibrios
      but that considerable microdiversity of unknown significance coexists within this
      trend.

PMID- 15240291
TI  - Effects of seeding procedures and water quality on recovery of Cryptosporidium
      oocysts from stream water by using U.S. Environmental Protection Agency Method
      1623.
AB  - U.S. Environmental Protection Agency method 1623 is widely used to monitor source
      waters and drinking water supplies for Cryptosporidium oocysts. Matrix spikes,
      used to determine the effect of the environmental matrix on the method's recovery
      efficiency for the target organism, require the collection and analysis of two
      environmental samples, one for analysis of endemic oocysts and the other for
      analysis of recovery efficiency. A new product, ColorSeed, enables the analyst to
      determine recovery efficiency by using modified seeded oocysts that can be
      differentiated from endemic organisms in a single sample. Twenty-nine stream
      water samples and one untreated effluent sample from a cattle feedlot were
      collected in triplicate to compare modified seeding procedures to conventional
      seeding procedures that use viable, unmodified oocysts. Significant negative
      correlations were found between the average oocyst recovery and turbidity or
      suspended sediment; this was especially apparent in samples with turbidities
      greater than 100 nephelometric turbidity units and suspended sediment
      concentrations greater than 100 mg/liter. Cryptosporidium oocysts were found in
      16.7% of the unseeded environmental samples, and concentrations, adjusted for
      recoveries, ranged from 4 to 80 oocysts per 10 liters. Determining recovery
      efficiency also provided data to calculate detection limits; these ranged from <2
      to <215 oocysts per 10 liters. Recoveries of oocysts ranged from 2.0 to 61% for
      viable oocysts and from 3.0 to 59% for modified oocysts. The recoveries between
      the two seeding procedures were highly correlated (r = 0.802) and were not
      significantly different. Recoveries by using modified oocysts, therefore, were
      comparable to recoveries by using conventional seeding procedures.

PMID- 15240292
TI  - Contribution of SAR11 bacteria to dissolved dimethylsulfoniopropionate and amino
      acid uptake in the North Atlantic ocean.
AB  - SAR11 bacteria are abundant in marine environments, often accounting for 35% of
      total prokaryotes in the surface ocean, but little is known about their
      involvement in marine biogeochemical cycles. Previous studies reported that SAR11
      bacteria are very small and potentially have few ribosomes, indicating that SAR11
      bacteria could have low metabolic activities and could play a smaller role in the
      flux of dissolved organic matter than suggested by their abundance. To determine
      the ecological activity of SAR11 bacteria, we used a combination of
      microautoradiography and fluorescence in situ hybridization (Micro-FISH) to
      measure assimilation of (3)H-amino acids and [(35)S]dimethylsulfoniopropionate
      (DMSP) by SAR11 bacteria in the coastal North Atlantic Ocean and the Sargasso
      Sea. We found that SAR11 bacteria were often abundant in surface waters,
      accounting for 25% of all prokaryotes on average. SAR11 bacteria were typically
      as large as, if not larger than, other prokaryotes. Additionally, more than half
      of SAR11 bacteria assimilated dissolved amino acids and DMSP, whereas about 40%
      of other prokaryotes assimilated these compounds. Due to their high abundance and
      activity, SAR11 bacteria were responsible for about 50% of amino acid
      assimilation and 30% of DMSP assimilation in surface waters. The contribution of
      SAR11 bacteria to amino acid assimilation was greater than would be expected
      based on their overall abundance, implying that SAR11 bacteria outcompete other
      prokaryotes for these labile compounds. These data suggest that SAR11 bacteria
      are highly active and play a significant role in C, N, and S cycling in the
      ocean.

PMID- 15240293
TI  - Use of the riboflavin synthase gene (ribC) as a model for development of an
      essential gene disruption and complementation system for Haemophilus influenzae.
AB  - We have developed a system for rapid and reliable assessment of gene essentiality
      in Haemophilus influenzae Rd strain KW20. We constructed two "suicide"
      complementation vectors (pASK5 and pASK6) containing 5' and 3' regions of the
      nonessential ompP1 gene flanking a multiple cloning site and a selectable marker
      (a chloramphenicol resistance gene or a tetracycline resistance cassette).
      Transformation of H. influenzae with the complementation constructs directs
      chromosomal integration of a gene of interest into the ompP1 locus, where the
      strong, constitutive ompP1 promoter drives its expression. This single-copy,
      chromosome-based complementation system is useful for confirming the essentiality
      of disrupted genes of interest. It allows genetic analysis in a background free
      of interference from any upstream or downstream genetic elements and enables
      conclusive assignment of essentiality. We validated this system by using the
      riboflavin synthase gene (ribC), a component of the riboflavin biosynthetic
      pathway. Our results confirmed the essentiality of ribC for survival of H.
      influenzae Rd strain KW20 and demonstrated that a complementing copy of ribC
      placed under control of the ompP1 promoter reverses the lethal phenotype of a
      strain with ribC deleted.

PMID- 15240294
TI  - Respiration strategies utilized by the gill endosymbiont from the host lucinid
      Codakia orbicularis (Bivalvia: Lucinidae).
AB  - The large tropical lucinid clam Codakia orbicularis has a symbiotic relationship
      with intracellular, sulfide-oxidizing chemoautotrophic bacteria. The respiration
      strategies utilized by the symbiont were explored using integrative techniques on
      mechanically purified symbionts and intact clam-symbiont associations along with
      habitat analysis. Previous work on a related symbiont species found in the host
      lucinid Lucinoma aequizonata showed that the symbionts obligately used nitrate as
      an electron acceptor, even under oxygenated conditions. In contrast, the
      symbionts of C. orbicularis use oxygen as the primary electron acceptor while
      evidence for nitrate respiration was lacking. Direct measurements obtained by
      using microelectrodes in purified symbiont suspensions showed that the symbionts
      consumed oxygen; this intracellular respiration was confirmed by using the redox
      dye CTC (5-cyano-2,3-ditolyl tetrazolium chloride). In the few intact
      chemosymbioses tested in previous studies, hydrogen sulfide production was shown
      to occur when the animal-symbiont association was exposed to anoxia and elemental
      sulfur stored in the thioautotrophic symbionts was proposed to serve as an
      electron sink in the absence of oxygen and nitrate. However, this is the first
      study to show by direct measurements using sulfide microelectrodes in enriched
      symbiont suspensions that the symbionts are the actual source of sulfide under
      anoxic conditions.

PMID- 15240295
TI  - Effect of substratum surface chemistry and surface energy on attachment of marine
      bacteria and algal spores.
AB  - Two series of self-assembled monolayers (SAMs) of omega-substituted
      alkanethiolates on gold were used to systematically examine the effects of
      varying substratum surface chemistry and energy on the attachment of two model
      organisms of interest to the study of marine biofouling, the bacterium Cobetia
      marina (formerly Halomonas marina) and zoospores of the alga Ulva linza (formerly
      Enteromorpha linza). SAMs were formed on gold-coated glass slides from solutions
      containing mixtures of methyl- and carboxylic acid-terminated alkanethiols and
      mixtures of methyl- and hydroxyl-terminated alkanethiols. C. marina attached in
      increasing numbers to SAMs with decreasing advancing water contact angles
      (theta(AW)), in accordance with equation-of-state models of colloidal attachment.
      Previous studies of Ulva zoospore attachment to a series of mixed methyl- and
      hydroxyl-terminated SAMs showed a similar correlation between substratum
      theta(AW) and zoospore attachment. When the hydrophilic component of the SAMs was
      changed to carboxylate, however, the profile of attachment of Ulva was
      significantly different, suggesting that a more complex model of interfacial
      energetics is required.

PMID- 15240296
TI  - Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes
      serotype 4b from foods.
AB  - Listeria monocytogenes contamination of ready-to-eat foods has been implicated in
      numerous outbreaks of food-borne listeriosis. However, the health hazards posed
      by L. monocytogenes detected in foods may vary, and speculations exist that
      strains actually implicated in illness may constitute only a fraction of those
      that contaminate foods. In this study, examination of 34 serogroup 4 (putative or
      confirmed serotype 4b) isolates of L. monocytogenes obtained from various foods
      and food-processing environments, without known implication in illness, revealed
      that many of these strains had methylation of cytosines at GATC sites in the
      genome, rendering their DNA resistant to digestion by the restriction
      endonuclease Sau3AI. These strains also harbored a gene cassette with putative
      restriction-modification system genes as well as other, genomically unlinked
      genetic markers characteristic of the major epidemic-associated lineage of L.
      monocytogenes (epidemic clone I), implicated in numerous outbreaks in Europe and
      North America. This may reflect a relatively high fitness of strains with these
      genetic markers in foods and food-related environments relative to other serotype
      4b strains and may partially account for the repeated involvement of such strains
      in human food-borne listeriosis.

PMID- 15240297
TI  - New real-time quantitative PCR procedure for quantification of bifidobacteria in
      human fecal samples.
AB  - The application of a real-time quantitative PCR method (5' nuclease assay), based
      on the use of a probe labeled at its 5' end with a stable, fluorescent lanthanide
      chelate, for the quantification of human fecal bifidobacteria was evaluated. The
      specificities of the primers and the primer-probe combination were evaluated by
      conventional PCR and real-time PCR, respectively. The results obtained by real
      time PCR were compared with those obtained by fluorescent in situ hybridization,
      the current gold standard for intestinal microbiota quantification. In general, a
      good correlation between the two methods was observed. In order to determine the
      detection limit and the accuracy of the real-time PCR procedure, germfree rat
      feces were spiked with known amounts of bifidobacteria and analyzed by both
      methods. The detection limit of the method used in this study was found to be
      about 5 x 10(4) cells per g of feces. Both methods, real-time PCR and fluorescent
      in situ hybridization, led to an accurate quantification of the spiked samples
      with high levels of bifidobacteria, but real-time PCR was more accurate for
      samples with low levels. We conclude that the real-time PCR procedure described
      here is a specific, accurate, rapid, and easy method for the quantification of
      bifidobacteria in feces.

PMID- 15240298
TI  - Identification of type A, B, E, and F botulinum neurotoxin genes and of botulinum
      neurotoxigenic clostridia by denaturing high-performance liquid chromatography.
AB  - Denaturing high-performance liquid chromatography (DHPLC) is a recently developed
      technique for rapid screening of nucleotide polymorphisms in PCR products. We
      used this technique for the identification of type A, B, E, and F botulinum
      neurotoxin genes. PCR products amplified from a conserved region of the type A,
      B, E, and F botulinum toxin genes from Clostridium botulinum, neurotoxigenic C.
      butyricum type E, and C. baratii type F strains were subjected to both DHPLC
      analysis and sequencing. Unique DHPLC peak profiles were obtained with each
      different type of botulinum toxin gene fragment, consistent with nucleotide
      differences observed in the related sequences. We then evaluated the ability of
      this technique to identify botulinal neurotoxigenic organisms at the genus and
      species level. A specific short region of the 16S rRNA gene which contains genus
      specific and in some cases species-specific heterogeneity was amplified from
      botulinum neurotoxigenic clostridia and from different food-borne pathogens and
      subjected to DHPLC analysis. Different peak profiles were obtained for each genus
      and species, demonstrating that the technique could be a reliable alternative to
      sequencing for the rapid identification of food-borne pathogens, specifically of
      botulinal neurotoxigenic clostridia most frequently implicated in human botulism.

PMID- 15240299
TI  - Chloromethane-dependent expression of the cmu gene cluster of Hyphomicrobium
      chloromethanicum.
AB  - The methylotrophic bacterium Hyphomicrobium chloromethanicum CM2 can utilize
      chloromethane (CH(3)Cl) as the sole carbon and energy source. Previously genes
      cmuB, cmuC, cmuA, and folD were shown to be essential for the growth of
      Methylobacterium chloromethanicum on CH(3)Cl. These CH(3)Cl-specific genes were
      subsequently detected in H. chloromethanicum. Transposon and marker exchange
      mutagenesis studies were carried out to identify the genes essential for CH(3)Cl
      metabolism in H. chloromethanicum. New developments in genetic manipulation of
      Hyphomicrobium are presented in this study. An electroporation protocol has been
      optimized and successfully applied for transformation of mutagenesis plasmids
      into H. chloromethanicum to generate stable CH(3)Cl-negative mutants. Both
      transposon and marker exchange mutageneses were highly applicable for genetic
      analysis of Hyphomicrobium. A reliable and reproducible selection procedure for
      screening of CH(3)Cl utilization-negative mutants has also been developed.
      Mutational inactivation of cmuB, cmuC, or hutI resulted in strains that were
      unable to utilize CH(3)Cl or to express the CH(3)Cl-dependent polypeptide CmuA.
      Reverse transcription-PCR analysis indicated that cmuB, cmuC, cmuA, fmdB, paaE,
      hutI, and metF formed a single cmuBCA-metF operon and were coregulated and
      coexpressed in H. chloromethanicum. This finding led to the conclusion that, in
      cmuB and cmuC mutants, impaired expression of cmuA was likely to be due to a
      polar effect of the defective gene (cmuB or cmuC) located upstream (5') of cmuA.
      The detrimental effect of mutation in hutI on the upstream (5')-located cmuA is
      not clear but indicated that all the genes located within the cmuBCA-metF operon
      are coordinately expressed. Expression of the cmuBCA-metF transcript was also
      shown to be strictly CH(3)Cl inducible and was not repressed by the alternative
      C(1) substrate methanol. Sequence analysis of a transposon mutant (D20) led to
      the discovery of the previously undetected hutI and metF genes located 3' of the
      paaE gene in H. chloromethanicum. MetF, a putative methylene-tetrahydrofolate
      reductase, had 27% identity to MetF from M. chloromethanicum. Mutational and
      transcriptional analysis data indicated that, in H. chloromethanicum, CH(3)Cl is
      metabolized via a corrinoid-specific (cmuA) and tetrahydrofolate-dependent (metF,
      purU, folD) methyltransfer system.

PMID- 15240300
TI  - Molecular analysis of shower curtain biofilm microbes.
AB  - Households provide environments that encourage the formation of microbial
      communities, often as biofilms. Such biofilms constitute potential reservoirs for
      pathogens, particularly for immune-compromised individuals. One household
      environment that potentially accumulates microbial biofilms is that provided by
      vinyl shower curtains. Over time, vinyl shower curtains accumulate films,
      commonly referred to as "soap scum," which microscopy reveals are constituted of
      lush microbial biofilms. To determine the kinds of microbes that constitute
      shower curtain biofilms and thereby to identify potential opportunistic
      pathogens, we conducted an analysis of rRNA genes obtained by PCR from four vinyl
      shower curtains from different households. Each of the shower curtain communities
      was highly complex. No sequence was identical to one in the databases, and no
      identical sequences were encountered in the different communities. However, the
      sequences generally represented similar phylogenetic kinds of organisms.
      Particularly abundant sequences represented members of the alpha-group of
      proteobacteria, mainly Sphingomonas spp. and Methylobacterium spp. Both of these
      genera are known to include opportunistic pathogens, and several of the sequences
      obtained from the environmental DNA samples were closely related to known
      pathogens. Such organisms have also been linked to biofilm formation associated
      with water reservoirs and conduits. In addition, the study detected many other
      kinds of organisms at lower abundances. These results show that shower curtains
      are a potential source of opportunistic pathogens associated with biofilms.
      Frequent cleaning or disposal of shower curtains is indicated, particularly in
      households with immune-compromised individuals.

PMID- 15240301
TI  - Regulation of Vibrio anguillarum empA metalloprotease expression and its role in
      virulence.
AB  - Atlantic salmon (Salmo salar) were challenged with Vibrio anguillarum strains
      M93Sm and NB10 and empA null mutants M99 and NB12. Both wild types were virulent
      when administered by intraperitoneal (i.p.) injection or anal intubation. NB12
      was avirulent via either route of infection. M99 virulence was attenuated when
      delivered by intubation, but fully virulent by i.p. injection. Northern blot
      analysis revealed empA expression in M93Sm and NB10 cells incubated in mucus,
      while incubation in Luria-Bertani broth plus 2% NaCl (LB20) induced empA
      expression only in NB10. Nucleotide differences between M93Sm and NB10 empA
      sequences were found in regions located 207 and 229 bp upstream of the empA
      translational start. Reverse transcription-PCR and 5' rapid amplification of cDNA
      ends revealed the empA transcriptional start site 85 bp upstream of the
      translational start for both strains. A putative sigma(S)-dependent promoter was
      identified upstream of the transcriptional start in both strains. Site-directed
      mutagenesis was used to create rpoS mutants of M93Sm and NB10. Neither rpoS
      mutant exhibited protease activity. Since empA is expressed during stationary
      phase, the effects of conditioned medium on protease activity were examined. M99
      conditioned LB20 supernatants stimulated protease activity in NB10 while allowing
      M93Sm to produce protease in LB20. Neither acyl homoserine lactones nor AI-2
      induced protease activity. Conditioned LB20 supernatant from a V. anguillarum
      luxS mutant caused a more rapid induction of protease activity in wild-type
      cells. Our data show that expression of empA is differentially regulated in V.
      anguillarum strains NB10 and M93Sm and requires sigma(S), quorum-sensing
      molecules, and gastrointestinal mucus.

PMID- 15240302
TI  - Effects of tylosin use on erythromycin resistance in enterococci isolated from
      swine.
AB  - The effect of tylosin on erythromycin-resistant enterococci was examined on three
      farms; farm A used tylosin for growth promotion, farm B used tylosin for
      treatment of disease, and farm C did not use tylosin for either growth promotion
      or disease treatment. A total of 1,187 enterococci were isolated from gestation,
      farrowing, suckling, nursery, and finishing swine from the farms. From a subset
      of those isolates (n = 662), 59% (124 out of 208), 28% (80 out of 281), and 2% (4
      out of 170) were resistant to erythromycin (MIC >/= 8 microg/ml) from farms A, B,
      and C, respectively. PCR analysis and Southern blotting revealed that 95% (65 out
      of 68) of isolates chosen from all three farms for further study were positive
      for ermB, but all were negative for ermA and ermC. By using Southern blotting,
      ermB was localized to the chromosome in 56 of the isolates while 9 isolates from
      farms A and B contained ermB on two similar-sized plasmid bands (12 to 16 kb).
      Pulsed-field gel electrophoresis revealed that the isolates were genetically
      diverse and represented a heterogeneous population of enterococci. This study
      suggests that although there was resistance to a greater number of enterococcal
      isolates on a farm where tylosin was used as a growth promotant, resistant
      enterococci also existed on a farm where no antimicrobial agents were used.

PMID- 15240303
TI  - Host-adapted Cryptosporidium spp. in Canada geese (Branta canadensis).
AB  - The prevalence and distribution of Cryptosporidium spp. in the fecal droppings of
      the free-living waterfowl Canada geese were examined at 13 sites in Ohio and
      Illinois. On the basis of the analysis of the small-subunit rRNA gene by PCR,
      followed by restriction fragment length polymorphism analysis and DNA sequencing,
      49 (23.4%) of 209 fecal specimens collected from 10 sites (76.9%) were positive
      for Cryptosporidium spp. The following five Cryptosporidium species and genotypes
      were identified: Cryptosporidium goose genotype I (in 36 specimens),
      Cryptosporidium goose genotype II (in 9 specimens), Cryptosporidium duck genotype
      (in 1 specimen), Cryptosporidium parvum (in 4 specimens), and C. hominis (in 2
      specimens). Cryptosporidium goose genotype I was the most prevalent parasite and
      was found at all five Cryptosporidium-positive sites in Ohio and at four of five
      positive sites in Illinois, followed by Cryptosporidium goose genotype II, which
      was found at two of five positive sites in Ohio and at four of five positive
      sites in Illinois. Cryptosporidium goose genotype II was detected for the first
      time, and it is phylogenetically related to goose genotype I and the duck
      genotype. All three genotypes have not so far been reported in humans, and their
      pathogenicity in geese has not been determined. Only 10.2% of the Cryptosporidium
      positive specimens had C. parvum and C. hominis. The results of this study
      indicate that Canada geese might only serve as accidental carriers of
      cryptosporidia infectious to humans and probably play a minor role in the animal
      to-human transmission cycle of the pathogen.

PMID- 15240304
TI  - Simultaneous discrimination between 15 fish pathogens by using 16S ribosomal DNA
      PCR and DNA microarrays.
AB  - We developed a DNA microarray suitable for simultaneous detection and
      discrimination between multiple bacterial species based on 16S ribosomal DNA
      (rDNA) polymorphisms using glass slides. Microarray probes (22- to 31-mer
      oligonucleotides) were spotted onto Teflon-masked, epoxy-silane-derivatized glass
      slides using a robotic arrayer. PCR products (ca. 199 bp) were generated using
      biotinylated, universal primer sequences, and these products were hybridized
      overnight (55 degrees C) to the microarray. Targets that annealed to microarray
      probes were detected using a combination of Tyramide Signal Amplification and
      Alexa Fluor 546. This methodology permitted 100% specificity for detection of 18
      microbes, 15 of which were fish pathogens. With universal 16S rDNA PCR (limited
      to 28 cycles), detection sensitivity for purified control DNA was equivalent to
      <150 genomes (675 fg), and this sensitivity was not adversely impacted either by
      the presence of competing bacterial DNA (1.1 x 10(6) genomes; 5 ng) or by the
      addition of up to 500 ng of fish DNA. Consequently, coupling 16S rDNA PCR with a
      microarray detector appears suitable for diagnostic detection and surveillance
      for commercially important fish pathogens.

PMID- 15240305
TI  - Osmotic stress response: quantification of cell maintenance and metabolic fluxes
      in a lysine-overproducing strain of Corynebacterium glutamicum.
AB  - Osmotic stress diminishes cell productivity and may cause cell inactivation in
      industrial fermentations. The quantification of metabolic changes under such
      conditions is fundamental for understanding and describing microbial behavior
      during bioprocesses. We quantified the gradual changes that take place when a
      lysine-overproducing strain of Corynebacterium glutamicum is grown in continuous
      culture with saline gradients at different dilution rates. The use of compatible
      solutes depended on environmental conditions; certain osmolites predominated at
      different dilution rates and extracellular osmolalities. A metabolic flux
      analysis showed that at high dilution rates C. glutamicum redistributed its
      metabolic fluxes, favoring energy formation over growth. At low dilution rates,
      cell metabolism accelerated as the osmolality was steadily increased. Flexibility
      in the oxaloacetate node proved to be key for the energetic redistribution that
      occurred when cells were grown at high dilution rates. Substrate and ATP
      maintenance coefficients increased 30- and 5-fold, respectively, when the
      osmolality increased, which demonstrates that energy pool management is
      fundamental for sustaining viability.

PMID- 15240306
TI  - Geomicrobiology of high-level nuclear waste-contaminated vadose sediments at the
      hanford site, washington state.
AB  - Sediments from a high-level nuclear waste plume were collected as part of
      investigations to evaluate the potential fate and migration of contaminants in
      the subsurface. The plume originated from a leak that occurred in 1962 from a
      waste tank consisting of high concentrations of alkali, nitrate, aluminate,
      Cr(VI), (137)Cs, and (99)Tc. Investigations were initiated to determine the
      distribution of viable microorganisms in the vadose sediment samples, probe the
      phylogeny of cultivated and uncultivated members, and evaluate the ability of the
      cultivated organisms to survive acute doses of ionizing radiation. The
      populations of viable aerobic heterotrophic bacteria were generally low, from
      below detection to approximately 10(4) CFU g(-1), but viable microorganisms were
      recovered from 11 of 16 samples, including several of the most radioactive ones
      (e.g., >10 microCi of (137)Cs/g). The isolates from the contaminated sediments
      and clone libraries from sediment DNA extracts were dominated by members related
      to known gram-positive bacteria. Gram-positive bacteria most closely related to
      Arthrobacter species were the most common isolates among all samples, but other
      phyla high in G+C content were also represented, including Rhodococcus and
      Nocardia. Two isolates from the second-most radioactive sample (>20 microCi of
      (137)Cs g(-1)) were closely related to Deinococcus radiodurans and were able to
      survive acute doses of ionizing radiation approaching 20 kGy. Many of the gram
      positive isolates were resistant to lower levels of gamma radiation. These
      results demonstrate that gram-positive bacteria, predominantly from phyla high in
      G+C content, are indigenous to Hanford vadose sediments and that some are
      effective at surviving the extreme physical and chemical stress associated with
      radioactive waste.

PMID- 15240307
TI  - Molecular analysis of carbon monoxide-oxidizing bacteria associated with recent
      Hawaiian volcanic deposits.
AB  - Genomic DNA extracts from four sites at Kilauea Volcano were used as templates
      for PCR amplification of the large subunit (coxL) of aerobic carbon monoxide
      dehydrogenase. The sites included a 42-year-old tephra deposit, a 108-year-old
      lava flow, a 212-year-old partially vegetated ash-and-tephra deposit, and an
      approximately 300-year-old forest. PCR primers amplified coxL sequences from the
      OMP clade of CO oxidizers, which includes isolates such as Oligotropha
      carboxidovorans, Mycobacterium tuberculosis, and Pseudomonas
      thermocarboxydovorans. PCR products were used to create clone libraries that
      provide the first insights into the diversity and phylogenetic affiliations of CO
      oxidizers in situ. On the basis of phylogenetic and statistical analyses, clone
      libraries for each site were distinct. Although some clone sequences were similar
      to coxL sequences from known organisms, many sequences appeared to represent
      phylogenetic lineages not previously known to harbor CO oxidizers. On the basis
      of average nucleotide diversity and average pairwise difference, a forested site
      supported the most diverse CO-oxidizing populations, while an 1894 lava flow
      supported the least diverse populations. Neither parameter correlated with
      previous estimates of atmospheric CO uptake rates, but both parameters correlated
      positively with estimates of microbial biomass and respiration. Collectively, the
      results indicate that the CO oxidizer functional group associated with recent
      volcanic deposits of the remote Hawaiian Islands contains substantial and
      previously unsuspected diversity.

PMID- 15240308
TI  - Enzymatic synthesis of high-molecular-mass poly-gamma-glutamate and regulation of
      its stereochemistry.
AB  - For the first time, we succeeded in synthesizing in vitro poly-gamma-glutamate
      (PGA) with high molecular masses (>1,000 kDa) by the use of enzyme-associated
      cell membranes from Bacillus subtilis subsp. chungkookjang. The activity for PGA
      synthesis, however, was readily lost in the presence of critical concentrations
      of detergents tested in micelles. The optimum pH for the reaction was found to be
      approximately 7.0. We examined the effects of some divalent cations on PGA
      synthesis and found that Mg(2+) was essential in catalysis and that Zn(2+)
      additionally boosted the activity. In contrast, Fe(2+) and Ca(2+) acted as
      inhibitors. Mn(2+) did not apparently influence the in vitro formation of PGA. DL
      Glutamate (D isomer content, 60 to 80%) apparently served as the best substrate;
      d-Glutamate was preferable to the L isomer as a substrate. When D- and L
      glutamate were used for the reaction, the elongated chains of PGAs were composed
      of the D- and L-isomers, respectively. Our results suggest that the
      stereochemical properties of enzymatically synthesized PGAs substantially depend
      on the stereochemistry (DL ratio) of glutamate as the substrate. Furthermore,
      genetic analysis indicated that all the pgsB, -C, and -A gene products, which are
      responsible for PGA production by B. subtilis cells, were also indispensable for
      enzymatic PGA synthesis.

PMID- 15240309
TI  - Natural atypical Listeria innocua strains with Listeria monocytogenes
      pathogenicity island 1 genes.
AB  - Identification of bona fide Listeria isolates into the six species of the genus
      normally requires only a few tests. Aberrant isolates do occur, but even then
      only one or two extra confirmatory tests are generally needed for identification
      to species level. We have discovered a hemolytic-positive, rhamnose and xylose
      fermentation-negative Listeria strain with surprising recalcitrance to
      identification to the species level due to contradictory results in standard
      confirmatory tests. The issue had to be resolved by using total DNA-DNA
      hybridization testing and then confirmed by further specific PCR-based tests
      including a Listeria microarray assay. The results show that this isolate is
      indeed a novel one. Its discovery provides the first fully documented instance of
      a hemolytic Listeria innocua strain. This species, by definition, is typically
      nonhemolytic. The L. innocua isolate contains all the members of the PrfA
      regulated virulence gene cluster (Listeria pathogenicity island 1) of L.
      monocytogenes. It is avirulent in the mouse pathogenicity test. Avirulence is
      likely at least partly due to the absence of the L. monocytogenes-specific allele
      of iap, as well as the absence of inlA, inlB, inlC, and daaA. At least two of the
      virulence cluster genes, hly and plcA, which encode the L. monocytogenes
      hemolysin (listeriolysin O) and inositol-specific phospholipase C, respectively,
      are phenotypically expressed in this L. innocua strain. The detection by PCR
      assays of specific L. innocua genes (lin0198, lin0372, lin0419, lin0558, lin1068,
      lin1073, lin1074, lin2454, and lin2693) and noncoding intergenic regions (lin0454
      lin0455 and nadA-lin2134) in the strain is consistent with its L. innocua DNA-DNA
      hybridization identity. Additional distinctly different hemolytic L. innocua
      strains were also studied.

PMID- 15240311
TI  - Solar and temporal effects on Escherichia coli concentration at a Lake Michigan
      swimming beach.
AB  - Studies on solar inactivation of Escherichia coli in freshwater and in situ have
      been limited. At 63rd St. Beach, Chicago, Ill., factors influencing the daily
      periodicity of culturable E. coli, particularly insolation, were examined. Water
      samples for E. coli analysis were collected twice daily between April and
      September 2000 three times a week along five transects in two depths of water.
      Hydrometeorological conditions were continuously logged: UV radiation, total
      insolation, wind speed and direction, wave height, and relative lake level. On 10
      days, transects were sampled hourly from 0700 to 1500 h. The effect of sunlight
      on E. coli inactivation was evaluated with dark and transparent in situ mesocosms
      and ambient lake water. For the study, the number of E. coli samples collected
      (n) was 2,676. During sunny days, E. coli counts decreased exponentially with day
      length and exposure to insolation, but on cloudy days, E. coli inactivation was
      diminished; the E. coli decay rate was strongly influenced by initial
      concentration. In situ experiments confirmed that insolation primarily
      inactivated E. coli; UV radiation only marginally affected E. coli concentration.
      The relationship between insolation and E. coli density is complicated by
      relative lake level, wave height, and turbidity, all of which are often products
      of wind vector. Continuous importation and nighttime replenishment of E. coli
      were evident. These findings (i) suggest that solar inactivation is an important
      mechanism for natural reduction of indicator bacteria in large freshwater bodies
      and (ii) have implications for management strategies of nontidal waters and the
      use of E. coli as an indicator organism.

PMID- 15240312
TI  - Metabolic engineering of mannitol production in Lactococcus lactis: influence of
      overexpression of mannitol 1-phosphate dehydrogenase in different genetic
      backgrounds.
AB  - To obtain a mannitol-producing Lactococcus lactis strain, the mannitol 1
      phosphate dehydrogenase gene (mtlD) from Lactobacillus plantarum was
      overexpressed in a wild-type strain, a lactate dehydrogenase(LDH)-deficient
      strain, and a strain with reduced phosphofructokinase activity. High-performance
      liquid chromatography and (13)C nuclear magnetic resonance analysis revealed that
      small amounts (<1%) of mannitol were formed by growing cells of mtlD
      overexpressing LDH-deficient and phosphofructokinase-reduced strains, whereas
      resting cells of the LDH-deficient transformant converted 25% of glucose into
      mannitol. Moreover, the formed mannitol was not reutilized upon glucose
      depletion. Of the metabolic-engineering strategies investigated in this work,
      mtlD-overexpressing LDH-deficient L. lactis seemed to be the most promising
      strain for mannitol production.

PMID- 15240310
TI  - Identification of bacterial populations in dairy wastewaters by use of 16S rRNA
      gene sequences and other genetic markers.
AB  - Hydraulic flush waste removal systems coupled to solid/liquid separators and
      circulated treatment lagoons are commonly utilized to manage the large amounts of
      animal waste produced on high-intensity dairy farms. Although these systems are
      common, little is known about the microbial populations that inhabit them or how
      they change as they traverse the system. Using culture-based and non-culture
      based methods, we characterized the microbial community structure of manure,
      water from the separator pit, and water from the circulated treatment lagoon from
      a large dairy in the San Joaquin Valley of California. Our results show that both
      total bacterial numbers and bacterial diversity are highest in manure, followed
      by the separator pit water and the lagoon water. The most prevalent phylum in all
      locations was the Firmicutes (low-G+C, gram-positive bacteria). The most commonly
      occurring operational taxonomic unit (OTU) had a 16S rRNA gene (rDNA) sequence 96
      to 99% similar to that of Clostridium lituseburense and represented approximately
      6% of the manure derived sequences, 14% of the separator pit-derived sequences
      and 20% of the lagoon-derived sequences. Also highly prevalent was an OTU with a
      16S rDNA sequence 97 to 100% similar to that of Eubacterium tenue, comprising
      approximately 3% of the manure-derived sequences, 6% of the separator pit-derived
      sequences and 9% of the lagoon-derived sequences. Taken together, these sequences
      represent approximately one-third of the total organisms in the lagoon waters,
      suggesting that they are well adapted to this environment.

PMID- 15240313
TI  - Presence of acylated homoserine lactones (AHLs) and AHL-producing bacteria in
      meat and potential role of AHL in spoilage of meat.
AB  - Quorum-sensing (QS) signals (N-acyl homoserine lactones [AHLs]) were extracted
      and detected from five commercially produced vacuum-packed meat samples. Ninety
      six AHL-producing bacteria were isolated, and 92 were identified as
      Enterobacteriaceae. Hafnia alvei was the most commonly identified AHL-producing
      bacterium. Thin-layer chromatographic profiles of supernatants from six H. alvei
      isolates and of extracts from spoiling meat revealed that the major AHL species
      had an R(f) value and shape similar to N-3-oxo-hexanoyl homoserine lactone
      (OHHL). Liquid chromatography-mass spectrometry (MS) (high-resolution MS)
      analysis confirmed the presence of OHHL in pure cultures of H. alvei. Vacuum
      packed meat spoiled at the same rate when inoculated with the H. alvei wild type
      compared to a corresponding AHL-lacking mutant. Addition of specific QS
      inhibitors to the AHL-producing H. alvei inoculated in meat or to naturally
      contaminated meat did not influence the spoilage of vacuum-packed meat. An
      extracellular protein of approximately 20 kDa produced by the H. alvei wild-type
      was not produced by the AHL-negative mutant but was restored in the mutant when
      complemented by OHHL, thus indicating that AHLs do have a regulatory role in H.
      alvei. Coinoculation of H. alvei wild-type with an AHL-deficient Serratia
      proteamaculans B5a, in which protease secretion is QS regulated, caused spoilage
      of liquid milk. By contrast, coinoculation of AHL-negative strains of H. alvei
      and S. proteamaculans B5a did not cause spoilage. In conclusion, AHL and AHL
      producing bacteria are present in vacuum-packed meat during storage and spoilage,
      but AHL does not appear to influence the spoilage of this particular type of
      conserved meat. Our data indicate that AHL-producing H. alvei may induce food
      quality-relevant phenotypes in other bacterial species in the same environment.
      H. alvei may thus influence spoilage of food products in which Enterobacteriaceae
      participate in the spoilage process.

PMID- 15240315
TI  - Restoration of a defective Lactococcus lactis xylose isomerase.
AB  - The genes (xylA) encoding xylose isomerase (XI) from two Lactococcus lactis
      subsp. lactis strains, 210 (Xyl(-)) and IO-1 (Xyl(+)), were cloned, and the
      activities of their expressed proteins in recombinant strains of Escherichia coli
      were investigated. The nucleotide and amino acid sequence homologies between the
      xylA genes were 98.4 and 98.6%, respectively, and only six amino acid residues
      differed between the two XIs. The purified IO-1 XI was soluble with K(m) and
      k(cat) being 2.25 mM and 184/s, respectively, while the 210 XI was insoluble and
      inactive. Site-directed mutagenesis on 210 xylA showed that a triple mutant
      possessing R202M/Y218D/V275A mutations regained XI activity and was soluble. The
      K(m) and k(cat) of this mutant were 4.15 mM and 141/s, respectively. One of the
      IO-1 XI mutants, S388T, was insoluble and showed negligible activity similar to
      that of 210 XI. The introduction of a K407E mutation to the IO-1 S388T XI mutant
      restored its activity and solubility. The dissolution of XI activity in L. lactis
      subsp. lactis involves a series of mutations that collectively eliminate enzyme
      activity by reducing the solubility of the enzyme.

PMID- 15240314
TI  - Detection of genes involved in biodegradation and biotransformation in microbial
      communities by using 50-mer oligonucleotide microarrays.
AB  - To effectively monitor biodegrading populations, a comprehensive 50-mer-based
      oligonucleotide microarray was developed based on most of the 2,402 known genes
      and pathways involved in biodegradation and metal resistance. This array
      contained 1,662 unique and group-specific probes with <85% similarity to their
      nontarget sequences. Based on artificial probes, our results showed that under
      hybridization conditions of 50 degrees C and 50% formamide, the 50-mer microarray
      hybridization can differentiate sequences having <88% similarity. Specificity
      tests with representative pure cultures indicated that the designed probes on the
      arrays appeared to be specific to their corresponding target genes. The detection
      limit was approximately 5 to 10 ng of genomic DNA in the absence of background
      DNA and 50 to 100 ng of pure-culture genomic DNA in the presence of background
      DNA or 1.3 x 10(7) cells in the presence of background RNA. Strong linear
      relationships between the signal intensity and the target DNA and RNA were
      observed (r(2) = 0.95 to 0.99). Application of this type of microarray to analyze
      naphthalene-amended enrichment and soil microcosms demonstrated that microflora
      changed differently depending on the incubation conditions. While the naphthalene
      degrading genes from Rhodococcus-type microorganisms were dominant in naphthalene
      degrading enrichments, the genes involved in naphthalene (and polyaromatic
      hydrocarbon and nitrotoluene) degradation from gram-negative microorganisms, such
      as Ralstonia, Comamonas, and Burkholderia, were most abundant in the soil
      microcosms. In contrast to general conceptions, naphthalene-degrading genes from
      Pseudomonas were not detected, although Pseudomonas is widely known as a model
      microorganism for studying naphthalene degradation. The real-time PCR analysis
      with four representative genes showed that the microarray-based quantification
      was very consistent with real-time PCR (r(2) = 0.74). In addition, application of
      the arrays to both polyaromatic-hydrocarbon- and benzene-toluene-ethylbenzene
      xylene-contaminated and uncontaminated soils indicated that the developed
      microarrays appeared to be useful for profiling differences in microbial
      community structures. Our results indicate that this technology has potential as
      a specific, sensitive, and quantitative tool in revealing a comprehensive picture
      of the compositions of biodegradation genes and the microbial community in
      contaminated environments, although more work is needed to improve detection
      sensitivity.

PMID- 15240316
TI  - Microscale and molecular assessment of impacts of nickel, nutrients, and oxygen
      level on structure and function of river biofilm communities.
AB  - Studies were carried out to assess the influence of nutrients, dissolved oxygen
      (DO) concentration, and nickel (Ni) on river biofilm development, structure,
      function, and community composition. Biofilms were cultivated in rotating annular
      reactors with river water at a DO concentration of 0.5 or 7.5 mg liter(-1), with
      or without a combination of carbon, nitrogen, and phosphorus (CNP) and with or
      without Ni at 0.5 mg liter(-1). The effects of Ni were apparent in the
      elimination of cyanobacterial populations and reduced photosynthetic biomass in
      the biofilm. Application of lectin-binding analyses indicated changes in
      exopolymer abundance and a shift in the glycoconjugate makeup of the biofilms, as
      well as in the response to all treatments. Application of the fluorescent live
      dead staining (BacLight Live-Dead staining kit; Molecular Probes, Eugene, Oreg.)
      indicated an increase in the ratio of live to dead cells under low-oxygen
      conditions. Nickel treatments had 50 to 75% fewer 'live' cells than their
      corresponding controls. Nickel at 0.5 mg liter(-1) corresponding to the
      industrial release rate concentration for nickel resulted in reductions in carbon
      utilization spectra relative to control and CNP treatments without nickel. In
      these cases, the presence of nickel eliminated the positive influence of
      nutrients on the biofilm. Other culture-dependent analyses (plate counts and most
      probable number) revealed no significant treatment effect on the biofilm
      communities. In the presence of CNP and at both DO levels, Ni negatively affected
      denitrification but had no effect on hexadecane mineralization or sulfate
      reduction. Analysis of total community DNA indicated abundant eubacterial 16S
      ribosomal DNA (rDNA), whereas Archaea were not detected. Amplification of the
      alkB gene indicated a positive effect of CNP and a negative effect of Ni. The
      nirS gene was not detected in samples treated with Ni at 0.5 mg liter(-1),
      indicating a negative effect on specific populations of bacteria, such as
      denitrifiers, resulting in a reduction in diversity. Denaturing gradient gel
      electrophoresis revealed that CNP had a beneficial impact on biofilm bacterial
      diversity at high DO concentrations, but none at low DO concentrations, and that
      the negative effect of Ni on diversity was similar at both DO concentrations.
      Notably, Ni resulted in the appearance of unique bands in 16S rDNA from Ni, DO,
      and CNP treatments. Sequencing results confirmed that the bands belonged to
      bacteria originating from freshwater and marine environments or from agricultural
      soils and industrial effluents. The observations indicate that significant
      interactions occur between Ni, oxygen, and nutrients and that Ni at 0.5 mg liter(
      1) may have significant impacts on river microbial community diversity and
      function.

PMID- 15240317
TI  - Development of a multispecies oral bacterial community in a saliva-conditioned
      flow cell.
AB  - Microbial communities within the human oral cavity are dynamic associations of
      more than 500 bacterial species that form biofilms on the soft and hard tissues
      of the mouth. Understanding the development and spatial organization of oral
      biofilms has been facilitated by the use of in vitro models. We used a saliva
      conditioned flow cell, with saliva as the sole nutritional source, as a model to
      examine the development of multispecies biofilm communities from an inoculum
      containing the coaggregation partners Streptococcus gordonii, Actinomyces
      naeslundii, Veillonella atypica, and Fusobacterium nucleatum. Biofilms inoculated
      with individual species in a sequential order were compared with biofilms
      inoculated with coaggregates of the four species. Our results indicated that flow
      cells inoculated sequentially produced biofilms with larger biovolumes compared
      to those biofilms inoculated with coaggregates. Individual-species biovolumes
      within the four-species communities also differed between the two modes of
      inoculation. Fluorescence in situ hybridization with genus- and species-specific
      probes revealed that the majority of cells in both sequentially and coaggregate
      inoculated biofilms were S. gordonii, regardless of the inoculation order.
      However, the representation of A. naeslundii and V. atypica was significantly
      higher in biofilms inoculated with coaggregates compared to sequentially
      inoculated biofilms. Thus, these results indicate that the development of
      multispecies biofilm communities is influenced by coaggregations preformed in
      planktonic phase. Coaggregating bacteria such as certain streptococci are
      especially adapted to primary colonization of saliva-conditioned surfaces
      independent of the mode of inoculation and order of addition in the multispecies
      inoculum. Preformed coaggregations favor other bacterial strains and may
      facilitate symbiotic relationships.

PMID- 15240319
TI  - Use of fluorescent lectin probes for analysis of footprints from Pseudomonas
      aeruginosa MDC on hydrophilic and hydrophobic glass substrata.
AB  - Microbial footprints of Pseudomonas aeruginosa MDC attached for 1 h to clean or
      silanized glass were analyzed with fluorescently labeled lectin probes. Footprint
      composition varied, depending on cell physiology and substratum surface
      chemistry. This suggests that substratum physicochemistry affected the structure
      of cell surfaces of adsorbed organisms.

PMID- 15240318
TI  - Fur is involved in manganese-dependent regulation of mntA (sitA) expression in
      Sinorhizobium meliloti.
AB  - Fur is a transcriptional regulator involved in iron-dependent control of gene
      expression in many bacteria. In this work we analyzed the phenotype of a fur
      mutant in Sinorhizobium meliloti, an alpha-proteobacterium that fixes N(2) in
      association with host plants. We demonstrated that some functions involved in
      high-affinity iron transport, siderophore production, and iron-regulated outer
      membrane protein expression respond to iron in a Fur-independent manner. However,
      manganese-dependent expression of the MntABCD manganese transport system was lost
      in a fur strain as discerned by constitutive expression of a mntA::gfp fusion
      reporter gene in the mutant. Thus, Fur directly or indirectly regulates a
      manganese-dependent function. The data indicate a novel function for a bacterial
      Fur protein in mediating manganese-dependent regulation of gene expression.

PMID- 15240320
TI  - Liquid serial dilution is inferior to solid media for isolation of cultures
      representative of the phylum-level diversity of soil bacteria.
AB  - Representatives of only four well-characterized bacterial phyla were isolated
      from a pasture soil by using liquid serial dilution culture. In contrast, members
      of Acidobacteria, Verrucomicrobia, and Gemmatimonadetes and of other poorly
      represented bacterial lineages were isolated in earlier experiments with
      solidified versions of the same media. We conclude that, contrary to expectation,
      liquid serial dilution culture is inferior to culturing on solid media for
      isolating representatives of many bacterial phyla from soil.

PMID- 15240321
TI  - Genotyping of Cryptosporidium isolates from Chamelea gallina clams in Italy.
AB  - Chamelea gallina clams collected from the mouths of rivers along the Adriatic Sea
      (central Italy) were found to harbor Cryptosporidium parvum (genotype 2), which
      is the lineage involved in zoonotic transmission. The clams were collected from
      the mouths of rivers near whose banks ruminants are brought to graze. This paper
      reports the environmental spread of C. parvum in Italy and highlights the fact
      that genotyping of seaborne Cryptosporidium isolates is a powerful tool with
      which to investigate the transmission patterns and epidemiology of this
      microorganism.

PMID- 15240322
TI  - Combined immunomagnetic separation-molecular beacon-reverse transcription-PCR
      assay for detection of hepatitis A virus from environmental samples.
AB  - In this study, a molecular-beacon-based real-time reverse transcription (RT)-PCR
      assay was developed to detect the presence of hepatitis A virus (HAV) in
      environmental samples. A 125-bp, highly conserved 5' noncoding region of HAV was
      targeted. The sensitivity of the real-time RT-PCR assay was tested with 10-fold
      dilutions of viral RNA, and a detection limit of 1 PFU was obtained. The
      specificity of the assay was demonstrated by testing with other environmental
      pathogens and indicator microorganisms, and only HAV was positively identified.
      When combined with immunomagnetic separation, the real-time RT-PCR assay
      successfully detected as few as 20 PFU in seeded groundwater samples. Because of
      its simplicity and specificity, this assay has broad applications for the rapid
      detection of HAV in contaminated foods or water.

PMID- 15240323
TI  - Comparison of shiga-toxigenic Escherichia coli prevalences among dairy, feedlot,
      and cow-calf herds in Washington State.
AB  - Shiga-toxigenic Escherichia coli (STEC) strains were isolated from 7.4% of 1,440
      fecal and farm environmental samples. Shiga toxin gene and STEC prevalences were
      significantly associated with animal production type and season. A range of
      serogroups were identified. Nine percent of isolates possessed all three
      principal virulence markers: stx(2), eae, and ehx.

PMID- 15240324
TI  - Validation of a PCR-based method for detection of food-borne thermotolerant
      campylobacters in a multicenter collaborative trial.
AB  - A PCR-based method for rapid detection of food-borne thermotolerant
      campylobacters was evaluated through a collaborative trial with 12 laboratories
      testing spiked carcass rinse samples. The method showed an interlaboratory
      diagnostic sensitivity of 96.7% and a diagnostic specificity of 100% for chicken
      samples, while these values were 94.2 and 83.3%, respectively, for pig samples.

PMID- 15240325
TI  - Degradation and turnover of extracellular DNA in marine sediments: ecological and
      methodological considerations.
AB  - Degradation rates of extracellular DNA determined in marine sediments were much
      higher than those in the water column. However, due to the high sediment DNA
      content, turnover times were much shorter in seawater. Results reported here
      provide new insights into the role of extracellular DNA in P cycling in marine
      ecosystems.

PMID- 15240326
TI  - Evidence for acyl homoserine lactone signal production in bacteria associated
      with marine sponges.
AB  - We report for the first time the production of acyl homoserine lactones (AHLs) by
      bacteria associated with marine sponges. Given the involvement of AHLs in
      bacterial colonization of many higher organisms, we speculate that such quorum
      sensing signals could play a part in interactions between sponges and the dense
      bacterial communities living within them.

PMID- 15240327
TI  - Online tool for analysis of denaturing gradient gel electrophoresis profiles.
AB  - We present an online tool (EquiBands,
      http://www.univie.ac.at/IECB/limno/equibands/EquiBands.html) that quantifies the
      matching of two bands considered to be the same in different samples, even when
      samples are applied to different denaturing gradient gel electrophoresis gels.
      With an environmental example we demonstrate the procedure for the classification
      of two bands of different samples with the help of EquiBands.

PMID- 15240328
TI  - Isolates of Piscirickettsia salmonis from Scotland and Ireland show evidence of
      clonal diversity.
AB  - Salmonid rickettsial septicemia, caused by Piscirickettsia salmonis, causes major
      mortalities in Chilean salmonid aquaculture and is an increasing problem in
      Atlantic salmon in Ireland and Scotland. Analysis of 16S-to-23S internal
      transcribed sequences and 16S ribosomal DNA (rDNA) shows that Irish isolates of
      P. salmonis form two new groups of the organism while Scottish isolates cluster
      together with Norwegian and Canadian isolates from Atlantic salmon.

PMID- 15240329
TI  - Degradation of alkyl ethers, aralkyl ethers, and dibenzyl ether by Rhodococcus
      sp. strain DEE5151, isolated from diethyl ether-containing enrichment cultures.
AB  - Twenty strains isolated from sewage sludge were found to degrade various ethers,
      including alkyl ethers, aralkyl ethers, and dibenzyl ether. In Rhodococcus strain
      DEE5151, induction of ether degradation needed substrates exhibiting at least one
      unsubstituted Calpha-methylene moiety as the main structural prerequisite. The
      cleavage reaction observed with anisole, phenetole, and dibenzyl ether indicates
      that the initial oxidation occurs at such respective Calpha positions. Diethyl
      ether-induced strain DEE5151 degraded dibenzyl ether via intermediately
      accumulated benzoic acid. Phenetole seems to be subject also to another ether
      cleaving enzyme. Other strains of this group showed different enzymatic
      activities towards the substrate classes investigated.

PMID- 15240330
TI  - Arthrobacter aurescens TC1 atrazine catabolism genes trzN, atzB, and atzC are
      linked on a 160-kilobase region and are functional in Escherichia coli.
AB  - Arthrobacter aurescens strain TC1 metabolizes atrazine to cyanuric acid via TrzN,
      AtzB, and AtzC. The complete sequence of a 160-kb bacterial artificial chromosome
      clone indicated that trzN, atzB, and atzC are linked on the A. aurescens genome.
      TrzN, AtzB, and AtzC were shown to be functional in Escherichia coli.
      Hybridization studies localized trzN, atzB, and atzC to a 380-kb plasmid in A.
      aurescens strain TC1.

PMID- 15240331
TI  - Influence of biosurfactants from probiotic bacteria on formation of biofilms on
      voice prostheses.
AB  - Biofilms were grown on preconditioned voice prostheses with biosurfactants
      obtained from probiotic bacteria Lactococcus lactis 53 and Streptococcus
      thermophilus A in an artificial throat model. Both biosurfactants greatly reduced
      microbial numbers on prostheses and also induced a decrease in the airflow
      resistance that occurs on voice prostheses after biofilm formation. This study
      presents a promising strategy for prolonging the lifespan of voice prostheses.

PMID- 15240332
TI  - Combining catalyzed reporter deposition-fluorescence in situ hybridization and
      microautoradiography to detect substrate utilization by bacteria and Archaea in
      the deep ocean.
AB  - The recently developed CARD-FISH protocol was refined for the detection of marine
      Archaea by replacing the lysozyme permeabilization treatment with proteinase K.
      This modification resulted in about twofold-higher detection rates for Archaea in
      deep waters. Using this method in combination with microautoradiography, we found
      that Archaea are more abundant than Bacteria (42% versus 32% of 4',6'-diamidino-2
      phenylindole counts) in the deep waters of the North Atlantic and that a larger
      fraction of Archaea than of Bacteria takes up l-aspartic acid (19% versus 10%).

PMID- 15240333
TI  - The interaction of asbestos and smoking in lung cancer: a modified measure of
      effect.
AB  - OBJECTIVES: The ratio of the relative risk of lung cancer due to asbestos
      exposure in non-smokers to that in smokers has been termed the relative asbestos
      effect (RAE). In a review, Liddell [Liddell FDK (2001) Ann Occup Hyg; 45: 341-56]
      estimated that the RAE was approximately 2. This measure is satisfactory when
      there is an appreciable relative risk due to asbestos but does not generalize to
      lower levels of exposure. A modified measure is proposed to overcome this
      difficulty. The modified measure, RAEm, is defined as the ratio of the excess
      relative risk (RR - 1) in non-smokers to that in smokers. METHODS: The cohort
      studies combined in Liddell's 2001 analysis have been used to give a combined
      estimate of the modified measure. RESULTS: The combined value of RAEm is 3.19
      with 95% confidence interval 1.67-6.13. CONCLUSION: The excess relative risk of
      lung cancer from asbestos exposure is about three times higher in non-smokers
      than in smokers. The modified measure has been placed within a more versatile
      model of interaction. If interaction is present the relative risk from asbestos
      exposure changes only slightly between light and heavy smokers, but is higher in
      very light smokers and non-smokers. The relative risk estimated from
      epidemiological studies of a mixed population of non-smokers and smokers applies
      to smokers.

PMID- 15240334
TI  - Noise exposure during alpine helicopter rescue operations.
AB  - OBJECTIVES: We estimated the noise exposure of crews working in alpine helicopter
      rescue systems. METHODS: Noise levels of the the helicopters used (Alouette III,
      Alouette II 'Lama', Ecureuil and BK 117) were measured with a device according to
      class 2 DIN IEC 651. These data were combined with the flight data of the
      personnel to evaluate the equivalent noise level according to DIN 45645-2.
      RESULTS AND CONCLUSIONS: While the risk to patients should be limited to
      temporary threshold shifts the crew members are regularly exposed to equivalent
      noise levels of >85 dB(A) and, therefore, are at risk of permanent threshold
      shifts. Consequences for crew fitness to fly and for noise prevention (crew and
      patients) are discussed.

PMID- 15240335
TI  - Particle deposition in industrial duct bends.
AB  - A study of particle deposition in industrial duct bends is presented. Particle
      deposition by size was measured by comparing particle size distributions upstream
      and downstream of bends that had geometries and flow conditions similar to those
      used in industrial ventilation. As the interior surface of the duct bend was
      greased to prevent particle bounce, the results are applicable to liquid drops
      and solid particles where duct walls are sticky. Factors investigated were: (i)
      flow Reynolds number (Re = 203 000, 36 000); (ii) particle Reynolds number (10 <
      Repinfinity < 200); (iii) particle Stokes number (0.08 < Stk < 16); (iv) bend
      angle (theta = 45 degrees, 90 degrees, 180 degrees ); (v) bend curvature ratio
      (1.7 < R0 < 12); (vi) orientation (horizontal-to-horizontal and horizontal-to
      vertical); and (vii) construction technique (smooth, gored, segmented). Measured
      deposition was compared with models developed for bends in small diameter
      sampling lines (Re < 20 000; Repinfinity < 13). Whereas deposition measured in
      this work generally agreed with that estimated with models for particles <30
      microm (Stk < 0.7), it was significantly lower than that estimated for larger
      particles. As the flow around larger particles became increasingly turbulent, the
      models progressively under-represented drag forces and over-estimated deposition.
      For particles >20 microm, deposition was slightly greater in the horizontal-to
      horizontal orientation than in the horizontal-to-vertical orientation due to
      gravitational settling. Penetration was not a multiplicative function of bend
      angle as theory predicts, due to the developing nature of turbulent flow in
      bends. Deposition in a smooth bend was similar to that in a gored bend; however,
      a tight radius segmented bend (R0 = 1.7) exhibited much lower deposition. For
      more gradual bends (3 < R0 < 12), curvature ratio had negligible effect on
      deposition.

PMID- 15240336
TI  - A stochastic differential equation for exposure yields a beta distribution.
AB  - This paper presents a stochastic differential equation for exposure based on a
      modified version of the standard dilution ventilation equation. An equilibrium
      solution is obtained with the assumption that variability in the rate of change
      of concentration is proportional to the product of concentration and one minus
      concentration. Appropriate definitions for concentration are used to ensure a
      physically consistent model. The probability distribution for exposure that
      results is the standard beta distribution. This model is supported by several
      exposure data sets, which fit the beta distribution well. Issues regarding
      parameter estimation for the beta distribution, and application of the model are
      presented. Recommendations are made for simultaneously collecting contaminant
      generation rate information, ventilation rates, and time-dependent breathing-zone
      tracer concentrations, in addition to the exposure data.

PMID- 15240337
TI  - A survey of airborne isocyanate exposure in 13 Swedish polyurethane industries.
AB  - Exposure to isocyanates can be harmful to workers by causing different disorders
      of the airways. The main objectives of this study were to survey the personal 8 h
      time-weighted average exposure to isocyanates at 13 Swedish plants that handled
      either polyurethane, diisocyanates or both, including four types of manufacturing
      processes: moulding, continuous foaming, flame lamination and low or no heating
      processes. A total of 223 air samples were collected for 111 workers with
      personal air monitoring using a dry filter method with 1-(2
      methoxyphenyl)piperazine (2MP) as derivatization reagent. A further 272
      stationary samples were collected, using the 2MP method, a modified 2MP method
      and an impinger method using dibutylamine in toluene. With the applied strategy,
      a large number of workers were monitored and four industrial environments were
      compared regarding the isocyanate exposure. All workers were found to be exposed
      to isocyanates in the range 0.004-5.2 p.p.b. On average, the personal exposure
      levels in the different types of manufacturing processes were, in decreasing
      order: continuous foaming > flame lamination > moulding >> low or no heating
      processes. However, there were variations in exposure levels in plants with
      similar processes and also between different shifts performing the same tasks.
      Isocyanic acid, which could not be sampled by the 2MP method used for personal
      monitoring, was found by short-term stationary monitoring in levels up to 38
      p.p.b. in the flame lamination plants.

PMID- 15240338
TI  - Determination of isocyanates in air using 1-(2-methoxyphenyl)piperazine
      impregnated filters: long-term sampling performance and field comparison with
      impingers with dibutylamine.
AB  - Isocyanates may be harmful to workers and methods for monitoring air exposure in
      the field are necessary. The main aim of this study was to study the field
      performance of a method using 1-(2-methoxyphenyl)piperazine (2MP)-impregnated
      filters, by side-by-side comparison of long-term sampling with consecutive short
      term samplings and also by short-term comparisons with other methods. Apart from
      using 2MP-impregnated filters, air monitoring was also performed by a modified
      2MP method (FINMP) and by an impinger method using dibutylamine (DBA), which was
      the reference method. For short-term sampling the compared methods performed
      equally well for 2,6-toluenediisocyanate (2,6-TDI) and for isocyanic acid. For
      2,4-toluenediisocyanate (2,4-TDI), the DBA method gave approximately 10% higher
      results according to linear regression than the 2MP method and for phenyl
      isocyanate, the DBA method gave significantly higher results than both the 2MP
      and FINMP methods. During long-term sampling (2-4 h) of TDI with the 2MP method,
      significantly lower levels were found compared with parallel sampling with
      consecutive short-term samplings. A time-dependent correction factor for long
      term sampling was calculated to be 1.7 for 2,4-TDI and 1.5 for 2,6-TDI for 4 h
      sampling. The long-term sampling performance for other isocyanates was not
      studied. In conclusion, short-term monitoring shows that the 2MP method slightly
      underestimates the true air concentration for some of the isocyanates studied,
      but the error is relatively small considering the variation in exposure. For long
      term monitoring the 2MP method can be applied for TDI but, since the method
      underestimates the concentrations, a correction factor is needed which needs to
      be corroborated further.

PMID- 15240339
TI  - Longitudinal study of sensitization to natural rubber latex among dental school
      students using powder-free gloves.
AB  - BACKGROUND: A high rate of sensitization and clinical allergy to latex proteins
      has been reported in health care personnel. This is thought to be due to
      increased occupational exposure especially to natural rubber latex (NRL) gloves
      with an estimated prevalence varying widely (2.8-18%). OBJECTIVE: This was a
      longitudinal study to monitor a cohort of first-year dental students throughout 4
      study years during exposure to powder-free gloves. Their atopic status was
      determined by skin prick testing using a panel of common allergens, and any
      sensitivity to latex proteins and the cross-reacting food allergens assessed.
      METHODS: Skin prick testing was carried out on the volunteers using latex,
      avocado, kiwi, banana, grass pollens, tree pollen, house dust mite and cat
      dander. Each volunteer completed a questionnaire detailing allergic history and
      any previous latex exposure. RESULTS: Skin prick testing showed a 65% incidence
      of atopy in the longitudinal study group. Initial latex skin testing was positive
      in 3 of the 63 students followed throughout their period of study. Subsequent
      testing gave a negative result in one student and one declined retesting. The
      third continued to give a positive response on each testing; she wore only
      nitrile gloves and remained free of clinical NRL allergy symptoms. No student
      developed latex sensitivity during the 5 yr of this study. CONCLUSION: Exposure
      to powder-free latex gloves was not associated with subsequent sensitization over
      5 yr in a population with a high atopic incidence.

PMID- 15240340
TI  - Personal exposure to ultrafine particles in the workplace: exploring sampling
      techniques and strategies.
AB  - Recently, toxicological and epidemiological studies on health effects related to
      particle exposure suggest that 'ultrafine particles' (particles with an
      aerodynamic diameter of <100 nm) may cause severe health effects after
      inhalation. Although the toxicological mechanisms for these effects have not yet
      been explained, it is apparent that measuring exposures against mass alone is not
      sufficient. It is also necessary to consider exposures against surface area and
      number concentration. From earlier research it was hypothesized that results on
      number concentration and particle distributions may vary with distance to the
      source, limiting the reliability of estimates of personal exposure from results
      which were obtained using static measurement equipment. Therefore, a workplace
      study was conducted to explore the performance of measurement methods in a multi
      source emission scenario as part of a sampling strategy to estimate personal
      exposure. In addition, a laboratory study was conducted to determine possible
      influences of both distance to source and time course on particle number
      concentration and particle size distribution. In both studies different
      measurement equipment and techniques were used to characterize (total) particle
      number concentration. These included a condensation particle counter (CPC), a
      scanning mobility particle sizer (SMPS) and an electrical low pressure impactor
      (ELPI). For the present studies CPC devices seemed to perform well for the
      identification of particle emission sources. The range of ultrafine particle
      number concentration can be detected by both SMPS and ELPI. An important
      advantage of the ELPI is that aerosols with ultrafine sizes can be collected for
      further analysis. Specific surface area of the aerosols can be estimated using
      gas adsorption analysis; however, with this technique ultrafine particles cannot
      be distinguished from particles with non-ultrafine sizes. Consequently, estimates
      based on samples collected from the breathing zone and scanning electron
      microscopic analysis may give a more reliable estimate of the specific surface
      area of the ultrafine particles responsible for personal exposure. The results of
      both the experimental and the workplace study suggest both spatial and temporal
      variation in total number concentration and aerosol size distribution. Therefore,
      the results obtained from static measurements and grab sampling should be
      interpreted with care as estimates of personal exposure. For evaluation of
      workplace exposure to ultrafine particles it is recommended that all relevant
      characteristics of such exposure are measured as part of a well-designed sampling
      strategy.

PMID- 15240341
TI  - Determinants of exposure to metalworking fluid aerosol in small machine shops.
AB  - The purpose of this study was to evaluate personal exposure to metalworking fluid
      (MWF) aerosols in very small machine shops (1-8 machinists per shop) and to
      investigate workplace factors associated with exposures. A total of 20 willing
      machine shops in Vancouver, Canada (from 46 eligible shops, 43%) and 88
      machinists participated (participation rate for machinists 92%). Most machinists
      wore two personal sampling trains (an open-faced 37 mm cassette and a PM10
      impactor) on each of two full work shifts. Observational data were collected
      regarding potential determinants of exposure at 15 min intervals throughout each
      shift. A total of 322 personal samples were taken over 54 days. Mean aerosol
      exposure was 0.32 mg/m3 (range 0.06-2.19) for the 37 mm cassette samples and 0.27
      mg/m3 (range 0.026-3.67) for PM10. Exposures from the two sampler types were
      highly correlated (R = 0.86). The mean shop-specific ratio comparing exposure
      from the 37 mm cassette with that from the PM10 sampler was 1.43 and varied
      significantly across shops, ranging from 0.97 to 2.19. Machine, task and shop
      characteristics associated with significantly increased aerosol exposure included
      the proportion of time spent grinding, operating an enclosed computer controlled
      machine, the presence of welding in the shop for both sampler types and the
      number of machines using MWF for PM10 samples only. Factors associated with
      reduced aerosol exposure included machining aluminum, milling, the height (and
      shape) of the shop roof (for both sample types) and the presence of mechanical
      shop ventilation (for the 37 mm cassette samples).

PMID- 15240342
TI  - Shear stress modulates the interaction of platelet-secreted matrix proteins with
      tumor cells through the integrin alphavbeta3.
AB  - Interaction of tumor cells with the vascular wall is required for metastasis from
      the bloodstream. The precise interaction among metastatic cells, circulating
      platelets, the vessel wall, and physiological flow conditions remains to be
      determined. In this study, we investigated the interaction of shear on metastatic
      cell lines adherent to lipopolysaccharide (LPS)-treated endothelium. Tumor cells
      were perfused over LPS-treated human umbilical vein endothelial cells (HUVECs) at
      incremental venous shear rates from 50 to 800 s(-1). At a venous shear rate of
      400 s(-1), 3% of adherent tumor cells formed pseudopodia under shear, a process
      we termed shear-induced activation. Because platelets promote tumor
      dissemination, we then investigated the effect of pretreating tumor cells with
      platelet releasate collected from activated platelet concentrate. We found that
      in the presence of platelet releasate, the number of tumor cells adhering to
      HUVECs increased and tumor "activation" occurred at a significantly lower shear
      rate of 50 s(-1). This was inhibited with acetylsalicylic acid. Depletion of
      fibronectin or vitronectin from the platelet releasate resulted in significantly
      less adhesion at higher venous shear rates of 600 and 800 s(-1). The integrin
      alphavbeta3 has been shown to mediate cell adhesion primarily through vitronectin
      and fibronectin proteins. Inhibition of alphavbeta3, followed by the addition of
      platelet releasate to the tumor cells, resulted in significantly less adhesion at
      higher venous shear rates of 600 and 800 s(-1). Collectively, our data suggest
      that alphavbeta3 promotes the metastatic phenotype of tumor cells through
      interactions with the secreted platelet proteins vitronectin and fibronectin
      under venous shear conditions.

PMID- 15240343
TI  - Inhibition of CFTR channels by a peptide toxin of scorpion venom.
AB  - Peptide toxins have been valuable probes in efforts to identify amino acid
      residues that line the permeation pathway of cation-selective channels. However,
      no peptide toxins have been identified that interact with known anion-selective
      channels such as the cystic fibrosis transmembrane conductance regulator (CFTR).
      CFTR channels are expressed in epithelial cells and are associated with several
      genetic disorders, including cystic fibrosis and polycystic kidney disease.
      Several organic inhibitors have been used to investigate the structure of the Cl-
      permeation pathway in CFTR. However, investigations of the wider cytoplasmic
      vestibule have been hindered by the lack of a high-affinity blocker that
      interacts with residues in this area. In this study we show that venom of the
      scorpion Leiurus quinquestriatus hebraeus reversibly inhibits CFTR, in a voltage
      independent manner, by decreasing single-channel mean burst duration and open
      probability only when applied to the cytoplasmic surface of phosphorylated
      channels. Venom was able to decrease burst duration and open probability even
      when CFTR channels were locked open by treatment with either vanadate or
      adenosine 5'-(beta,gamma-imido)triphosphate, and block was strengthened on
      reduction of extracellular Cl- concentration, suggesting inhibition by a pore
      block mechanism. Venom had no effect on ATP-dependent macroscopic opening rate in
      channels studied by inside-out macropatches. Interestingly, the inhibitory
      activity was abolished by proteinase treatment. We conclude that a peptide toxin
      contained in the scorpion venom inhibits CFTR channels by a pore-block mechanism;
      these experiments provide the first step toward isolation of the active
      component, which would be highly valuable as a probe for CFTR structure and
      function.

PMID- 15240344
TI  - Inhibition of cell cycle progression and migration of vascular smooth muscle
      cells by prostaglandin D2 synthase: resistance in diabetic Goto-Kakizaki rats.
AB  - The regulation of vascular smooth muscle cell (VSMC) proliferation, migration,
      and apoptosis plays a clear role in the atherosclerotic process. Recently, we
      reported on the inhibition of the exaggerated growth phenotype of VSMCs isolated
      from hypertensive rats by lipocalin-type prostaglandin D2 synthase (L-PGDS). In
      the present study, we report the differential effects of L-PGDS on VSMC cell
      cycle progression, migration, and apoptosis in wild-type VSMCs vs. those from a
      type 2 diabetic model. In wild-type VSMCs, exogenously added L-PGDS delayed serum
      induced cell cycle progression from the G1 to S phase, as determined by gene
      array analysis and the decreased protein expressions of cyclin-dependent kinase
      2, p21(Cip1), and cyclin D1. Cyclin D3 protein expression was unaffected by L
      PGDS, although its gene expression was stimulated by L-PGDS in wild-type cells.
      In addition, platelet-derived growth factor-induced VSMC migration was inhibited
      by L-PGDS in wild-type cells. Type 2 diabetic VSMCs, however, were resistant to
      the L-PGDS effects on cell cycle progression and migration. L-PGDS did suppress
      the hyperproliferation of diabetic cells, albeit through a different mechanism,
      presumably involving the 2.5-fold increase in apoptosis and the concomitant 10
      fold increase of L-PGDS uptake we observed in these cells. We propose that in
      wild-type VSMCs, L-PGDS retards cell cycle progression and migration, precluding
      hyperplasia of the tunica media, and that diabetic cells appear resistant to the
      inhibitory effects of L-PGDS, which consequently may help explain the increased
      atherosclerosis observed in diabetes.

PMID- 15240345
TI  - Glycolate and glyoxylate metabolism in HepG2 cells.
AB  - Oxalate synthesis in human hepatocytes is not well defined despite the clinical
      significance of its overproduction in diseases such as the primary
      hyperoxalurias. To further define these steps, the metabolism to oxalate of the
      oxalate precursors glycolate and glyoxylate and the possible pathways involved
      were examined in HepG2 cells. These cells were found to contain oxalate,
      glyoxylate, and glycolate as intracellular metabolites and to excrete oxalate and
      glycolate into the medium. Glycolate was taken up more effectively by cells than
      glyoxylate, but glyoxylate was more efficiently converted to oxalate. Oxalate was
      formed from exogenous glycolate only when cells were exposed to high
      concentrations. Peroxisomes in HepG2 cells, in contrast to those in human
      hepatocytes, were not involved in glycolate metabolism. Incubations with purified
      lactate dehydrogenase suggested that this enzyme was responsible for the
      metabolism of glycolate to oxalate in HepG2 cells. The formation of 14C-labeled
      glycine from 14C-labeled glycolate was observed only when cell membranes were
      permeabilized with Triton X-100. These results imply that peroxisome permeability
      to glycolate is restricted in these cells. Mitochondria, which produce glyoxylate
      from hydroxyproline metabolism, contained both alanine:glyoxylate
      aminotransferase (AGT)2 and glyoxylate reductase activities, which can convert
      glyoxylate to glycine and glycolate, respectively. Expression of AGT2 mRNA in
      HepG2 cells was confirmed by RT-PCR. These results indicate that HepG2 cells will
      be useful in clarifying the nonperoxisomal metabolism associated with oxalate
      synthesis in human hepatocytes.

PMID- 15240346
TI  - Munc-18-2 regulates exocytosis of H(+)-ATPase in rat inner medullary collecting
      duct cells.
AB  - Exocytic insertion of H(+)-ATPase into the apical membrane of inner medullary
      collecting duct (IMCD) cells is dependent on a soluble N-ethylmaleimide-sensitive
      factor (NSF) attachment protein target receptor (SNARE) complex. In this study we
      determined the role of Munc-18 in regulation of IMCD cell exocytosis of H(+)
      ATPase. We compared the effect of acute cell acidification (the stimulus for IMCD
      exocytosis) on the interaction of syntaxin 1A with Munc-18-2 and the 31-kDa
      subunit of H(+)-ATPase. Immunoprecipitation revealed that cell acidification
      decreased green fluorescent protein (GFP)-syntaxin 1A and Munc-18-2 interaction
      by 49 +/- 7% and increased the interaction between GFP-syntaxin 1A and H(+)
      ATPase by 170 +/- 23%. Apical membrane Munc-18-2 decreased by 27.5 +/- 4.6% and
      H(+)-ATPase increased by 246 +/- 22%, whereas GP-135, an apical membrane marker,
      did not increase. Pretreatment of IMCD cells with a PKC inhibitor (GO-6983)
      diminished the previously described changes in Munc-18-2-syntaxin 1A interaction
      and redistribution of H(+)-ATPase. In a pull-down assay of H(+)-ATPase by
      glutathione S-transferase (GST)-syntaxin 1A bound to beads, preincubation of
      beads with an approximately twofold excess of His-Munc-18-2 decreased H(+)-ATPase
      pulled down by 64 +/- 16%. IMCD cells that overexpress Munc-18-2 had a reduced
      rate of proton transport compared with control cells. We conclude that Munc-18-2
      must dissociate from the syntaxin 1A protein for the exocytosis of H(+)-ATPase to
      occur. This dissociation leads to a conformational change in syntaxin 1A,
      allowing it to interact with H(+)-ATPase, synaptosome-associated protein (SNAP)
      23, and vesicle-associated membrane protein (VAMP), forming the SNARE complex
      that leads to the docking and fusion of H(+)-ATPase vesicles.

PMID- 15240347
TI  - Hormones and the stressed brain.
AB  - The stress system orchestrates brain and body responses to the environment.
      Cortisol (in humans) or corticosterone (in rodents) are important mediators of
      the stress system. Their action-in concert-is crucial for individual differences
      in coping with other individuals, which in turn depend on genetic- and experience
      related factors. The actions exerted by cortisol and corticosterone have an
      enormous diversity. They include the regulation of rapid molecular aggregations,
      membrane processes, and gene transcription. In the latter transcriptional
      regulation, the corticosteroid hormones have two modes of operation. One mode is
      mediated by high-affinity mineralocorticoid receptors (MRs), which control gene
      networks underlying stabilization of neuronal activity as determinant for the
      sensitivity to trigger immediate responses to stress organized by corticotrophin
      releasing hormone (CRH)-1 receptor. Whereas disturbance of homeostasis is
      prevented by MR-mediated processes, its recovery is facilitated via the low
      affinity glucocorticoid receptors (GRs) that require stress levels of cortisol.
      GRs promote in coordination with CRH-2 receptors and the parasympathetic system
      behavioral adaptation and enhances storage of energy and information in
      preparation for future events. The balance in the two stress system modes is
      thought to be essential for cell homeostasis, mental performance, and health.
      Imbalance induced by genetic modification or stressors changes specific neural
      signaling pathways underlying cognition and emotion. This yin-yang concept in
      stress regulation is fundamental for genomic strategies to understand the
      mechanistic underpinning of corticosteroid-induced stress-related disorders such
      as severe forms of depression.

PMID- 15240348
TI  - Localization and chemical characterization of the audiogenic stress pathway.
AB  - Neuronal pathways involved in stress responses to extreme somatosensory stimuli
      were investigated by immunostaining, viral tract tracing, and experimental brain
      surgery in rats. Acute audiogenic stress, which elicits an immediate marked
      elevation in plasma ACTH and corticosterone concentrations, was used as a model.
      Loud noise (105 dB, 30 min) elicited c-fos activation within neurons in all of
      the components of the auditory system and stress-sensitive brain nuclei,
      including corticotropin-releasing hormone-synthesizing parvicellular neurons in
      the hypothalamic paraventricular nucleus (PVN). c-Fos activation was also seen in
      the medial paralemniscal nucleus in the pons (MPL) and in the subparafascicular
      nucleus (SPF) in the midbrain. After injection of neurotropic virus
      (pseudorabies, Bartha strain) into the PVN, neurons in the MPL and the
      parvicellular portion of the SPF were retrogradely infected. It has been shown by
      immunostaining that MPL and SPF neurons express a newly discovered neuropeptide,
      tuberoinfundibular peptide of 39 residues (TIP39). TIP39 is present in a fine
      neuronal network in the PVN. Audiogenic stress-elicited c-fos activation in TIP39
      containing neurons of the MPL and SPF. TIP39 immunoreactivity disappeared from
      the PVN after transection of MPL and SPF projections to the nucleus. These
      observations suggest that TIP39-containing MPL and SPF neurons may participate in
      mediating audiogenic stress responses.

PMID- 15240349
TI  - Brain circuits involved in corticotropin-releasing factor-norepinephrine
      interactions during stress.
AB  - Corticotropin-releasing factor (CRF)- and norepinephrine (NE)-containing neurons
      in the brain are activated during stress, and both have been implicated in the
      behavioral responses. NE neurons in the brain stem can stimulate CRF neurons in
      the hypothalamic paraventricular nucleus (PVN) to activate the hypothalamic
      pituitary-adrenocortical axis and may affect other CRF neurons. CRF-containing
      neurons in the PVN, the amygdala, and other brain areas project to the area of
      the locus coeruleus (LC), and CRF injected into the LC alters the
      electrophysiologic activity of LC-NE neurons. Neurochemical studies have
      indicated that CRF applied intracerebroventricularly or locally activates the LC
      NE system, and microdialysis and chronoamperometric measurements indicate
      increased NE release in LC-NE terminal fields. However, chronoamperometric
      studies indicated a significant delay in the increase in NE release, suggesting
      that the CRF input to LC-NE neurons is indirect. The reciprocal interactions
      between cerebral NE and CRF systems have been proposed to create a "feed-forward"
      loop. It has been postulated that a sensitization of such a feed-forward loop may
      underlie clinical depression. However, in the majority of studies, repeated or
      chronic stress has been shown to decrease the behavioral and the neurochemical
      responsivity to acute stressors. Repeated stress also seems to decrease the
      responsivity of LC neurons to CRF. These results do not provide support for a
      feed-forward hypothesis. However, a few studies using certain tasks have
      indicated sensitization, and some other studies have suggested that the effect of
      CRF may be dose dependent. Further investigations are necessary to establish the
      validity or otherwise of the feed-forward hypothesis.

PMID- 15240350
TI  - Role of GABA and glutamate circuitry in hypothalamo-pituitary-adrenocortical
      stress integration.
AB  - GABA and glutamate play a major role in central integration of hypothalamo
      pituitary-adrenocortical (HPA) stress responses. Recent work in our group has
      focused on mechanisms whereby GABAergic and glutamatergic circuits interact with
      parvocellular paraventricular nucleus (PVN) neurons controlling the HPA axis.
      GABAergic neurons in the bed nucleus of the stria terminalis, preoptic area, and
      hypothalamus can directly inhibit PVN outflow and thereby reduce ACTH secretion.
      In contrast, glutamate activates the HPA axis, presumably by way of hypothalamic
      and brainstem projections to the PVN. These inhibitory and excitatory PVN
      projecting neurons are controlled by descending information from limbic forebrain
      structures, including glutamatergic neurons of the ventral subiculum, prefrontal
      cortex, and GABAergic cells from the amygdala and perhaps septum. Lesion studies
      indicate that the ventral subiculum and prefrontal cortex are involved in
      inhibition of HPA axis responses to psychogenic stimuli, whereas the amygdala is
      positioned to enhance hormone secretion by way of GABA-GABA disinhibitory
      connections. Thus, it seems the psychogenic responses to stress are gated by
      discrete sets of GABAergic neurons in the basal forebrain and hypothalamus. As
      such, these neurons are positioned to summate limbic inputs into net inhibitory
      tone on the PVN and may thus play a major role in HPA dysfunction seen in
      affective disease states and aging.

PMID- 15240351
TI  - Anatomic and functional topography of the dorsal raphe nucleus.
AB  - Serotonergic systems play an important and generalized role in regulation of
      sleep-wake states and behavioral arousal. Recent in vivo electrophysiologic
      recording studies in animals suggest that several different subtypes of
      serotonergic neurons with unique behavioral correlates exist within the brainstem
      raphe nuclei, raising the possibility that topographically organized
      subpopulations of serotonergic neurons may have unique behavioral or physiologic
      correlates and unique functional properties. We have shown that the stress
      related and anxiogenic neuropeptide corticotropin-releasing factor can stimulate
      the in vitro neuronal firing rates of topographically organized subpopulations of
      serotonergic neurons within the dorsal raphe nucleus (DR). These findings are
      consistent with a wealth of behavioral studies suggesting that serotonergic
      systems within the DR are involved in the modulation of ongoing anxiety-related
      behavior and in behavioral sensitization, a process whereby anxiety- and fear
      related behavioral responses are sensitized for a period of up to 24 to 48 h. The
      dorsomedial subdivision of the DR, particularly its middle and caudal aspects,
      has attracted considerable attention as a region that may play a critical role in
      the regulation of acute and chronic anxiety states. Future studies aimed at
      characterization of the molecular and cellular properties of topographically
      organized subpopulations of serotonergic neurons are likely to lead to major
      advances in our understanding of the role of serotonergic systems in stress
      related physiology and behavior.

PMID- 15240352
TI  - A functional subset of serotonergic neurons in the rat ventrolateral
      periaqueductal gray implicated in the inhibition of sympathoexcitation and panic.
AB  - The ability of serotonin (5-HT) to facilitate or attenuate autonomic, endocrine,
      and behavioral responses to stressful stimuli has received much attention. The
      effects of 5-HT on physiologic and behavioral responses to stressful stimuli seem
      to depend on the brain region where it is released and the effector system it
      acts upon. This and the distinct morphology and topographic organization of
      subpopulations of serotonergic neurons have led to the hypothesis that
      subpopulations of serotonergic neurons are functionally distinct. Serotonin's
      role as a modulator of the "fight-or-flight" response is mediated in part by 5-HT
      release in the dorsolateral periaqueductal gray (DLPAG) and in the rostral
      ventrolateral medulla (RVLM), an area that contains sympathoexcitatory C1
      adrenergic (A) neurons. The release of 5-HT in either region inhibits stress
      induced sympathetic activity in part via actions on 5-HT(1A) receptors. In
      addition, 5-HT release in the DLPAG inhibits fight-or-flight or "Go" behaviors.
      The origin of endogenous 5-HT in the DLPAG and RVLM seems to be a subpopulation
      of serotonergic neurons within the ventrolateral PAG, a region implicated in
      "freezing" or "No Go" behaviors. These serotonergic neurons are located in the
      lateral "wings" of the dorsal raphe nucleus (DRN) a region also referred to as
      the ventrolateral DRN. The existence of a functional subpopulation of
      serotonergic neurons capable of inhibiting sympathoexcitation and fight-or-flight
      behavioral responses may be clinically relevant for explaining in part the
      efficacy of serotonergic drugs in the treatment of hypertension and panic attacks
      in panic disorder patients.

PMID- 15240353
TI  - Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis:
      interaction between 5-HT1A and 5-HT2A receptors.
AB  - Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective
      serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT
      receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma
      corticosterone levels, and it is likely that these receptor subtypes are central
      to mediating the effects of SSRIs. To study the interaction of these receptors,
      rats were administered with the 5-HT(1A/7) agonist 8-OH-DPAT (0.05 to 1.25
      mg/kg), the 5-HT(2A/C) agonist DOI (0.25 to 5 mg/kg), or a mixture of both
      compounds, and trunk blood was taken 60 min later. The two compounds given in
      combination produced a lower increase in corticosterone than DOI does alone. DOI
      and 8-OH-DPAT also produced a marked induction of c-Fos in the paraventricular
      nucleus (PVN), but the induction was not different if the two compounds were
      given together. These data show that the two serotonin receptor subtypes affect
      the HPA axis via a central target. In conclusion, 5-HT(1A) and 5-HT(2A) receptors
      regulate corticotrophin-releasing hormone (CRH) neurons via distinct but strongly
      interacting pathways, probably converging on the same neurons in the
      hypothalamus.

PMID- 15240354
TI  - Integration of systemic and visceral sensory information by medullary
      catecholaminergic systems during peripheral inflammation.
AB  - The nucleus of the solitary tract (nTS) is topographically organized with respect
      to the distribution of afferent sensory innervation and efferent projection
      patterns. Evidence suggests that the cells within the nTS, including medullary
      catecholaminergic (CA) neurons, are functionally diverse and that during
      peripheral inflammation they are recruited in a topographically organized manner
      that reflects their associations with afferent sensory systems. It is therefore
      feasible that topographically organized subdivisions of the nTS and the medullary
      CA neurons contained within them are differentially involved in signaling
      systemic (e.g., derived from blood-borne signals) versus visceral sensory
      information (e.g., derived from afferent sensory signals within the vagus nerve)
      during peripheral inflammation. The purpose of this review is to summarize (1)
      the topographic organization of afferent sensory input from vagal and systemic
      signaling pathways to the nTS in relation to medullary CA neurons and (2) the
      functional evidence to support the differential involvement of topographically
      organized subpopulations of CA and non-CA neurons in relaying signals of visceral
      versus systemic sensory information.

PMID- 15240355
TI  - Brain angiotensin II, an important stress hormone: regulatory sites and
      therapeutic opportunities.
AB  - The presence of a brain Angiotensin II (Ang II) system, separated from and
      physiologically integrated with the peripheral, circulating renin-angiotensin
      system, is firmly established. Ang II is made in the brain and activates specific
      brain AT(1) receptors to regulate thirst and fluid metabolism. Some AT(1)
      receptors are located outside the blood-brain barrier and are sensitive to brain
      and circulating Ang II. Other AT(1) receptors, located inside the blood-brain
      barrier, respond to stimulation by Ang II of brain origin. AT(1) receptors in the
      subfornical organ, the hypothalamic paraventricular nucleus (PVN), and the median
      eminence are involved in the regulation of the stress response. In particular,
      AT(1) receptors in the PVN are under glucocorticoid control and regulate
      corticotrophin-releasing hormone (CRH) formation and release. In the PVN,
      restraint elicits a fast increase in AT(1) receptor mRNA expression. The
      expression of paraventricular AT(1) receptors is increased during repeated
      restraint and after 24 h of isolation stress, and their stimulation is essential
      for the hypothalamic-pituitary-adrenal axis activation, the hallmark of the
      stress response. Peripheral administration of an AT(1) receptor antagonist blocks
      peripheral and brain AT(1) receptors, prevents the sympathoadrenal and hormonal
      response to isolation stress, and prevents the gastric stress ulcers that are a
      characteristic consequence of cold-restraint stress. This evidence indicates that
      pharmacologic inhibition of the peripheral and brain Ang II system by AT(1)
      receptor blockade has a place in the prevention and treatment of stress-related
      disorders.

PMID- 15240356
TI  - From brain to blood: alternative splicing evidence for the cholinergic basis of
      Mammalian stress responses.
AB  - Three principal features of mammalian stress responses are that they span
      peripheral and CNS changes, modify blood cell composition and activities, and
      cover inter-related alterations in a large number of gene products. The finely
      tuned spatiotemporal regulation of these multiple events suggests the hierarchic
      involvement of modulatory neurotransmitters and modified process(es) in the
      pathway of gene expression that together would enable widely diverse stress
      responses. We report evidence supporting the notion that acetylcholine (ACh) acts
      as a stress-response-regulating transmitter and that altered ACh levels are
      variously associated with changes in the alternative splicing of pre-mRNA
      transcripts in brain neurons and peripheral blood cells. We used
      acetylcholinesterase (AChE) gene expression as a case study and developed
      distinct probes for its alternative splice variants at the mRNA and protein
      levels. In laboratory animals and human-derived cells, we found stress-induced
      changes in the alternative splicing patterns of AChE pre-mRNA, which attributes
      to this gene and its different protein products diverse stress responsive
      functions that are associated with the enzymatic and noncatalytic properties of
      AChE. Together, these approaches provide a conceptually unified view of the
      studied pathways for controlling stress responses in brain and blood.

PMID- 15240357
TI  - Life-long serotonin reuptake deficiency results in complex alterations in
      adrenomedullary responses to stress.
AB  - This study examined whether serotonin transporter (SERT) deficiency influences
      adrenal serotonin (5-HT), catecholamine and Angiotensin II (Ang II) systems, and
      the hormonal response to acute restraint stress. Control SERT mice (+/+)
      expressed high numbers of SERT binding sites in adrenal medulla. Fifteen minutes
      of restraint stress increased adrenal 5-HT, adrenomedullary tyrosine hydroxylase
      (TH) mRNA expression and plasma epinephrine (EPI), and norepinephrine levels
      without alterations in adrenal catecholamine content. In SERT+/+, these responses
      coincided with a significant increase in adrenomedullary Ang II AT(2) receptor
      expression. SERT-deficient mice did not express SERT binding sites; their adrenal
      5-HT was significantly depleted and further reduced after stress. They had
      exaggerated stress-induced EPI release into plasma, the increase in TH
      transcription did not occur, adrenal catecholamine content was decreased compared
      with SERT+/+, and stress induced a reduction rather than increase in the number
      of adrenomedullary AT(2) receptors. SERT-/- mice also possessed decreased
      pituitary 5-HT. Their pituitary ACTH was reduced after stress, but stress-induced
      increases in plasma ACTH and corticosterone were not different from those of
      SERT+/+ mice. Our results indicate that SERT function not only restrains stress
      induced EPI release but also is required for the increase in adrenal
      catecholamine synthesis and AT(2) receptor expression.

PMID- 15240358
TI  - Inhibitory effect of formalin administration on immobilization-induced
      epinephrine release.
AB  - Injection of formalin is used as a classical painful stressor that produces a
      biphasic nociceptive response consisting of a 1- to 10-min early phase and a
      later phase 30 to 240 min after injection. The period between these two phases,
      called "interphase," is characterized by attenuated nociception. We evaluated the
      response of catecholamine plasma levels to formalin-induced pain stress with
      special attention to these three time periods. Subcutaneous injection of 4%
      formalin (0.2 mL/100 g bw) into the hind limb produced a slight reduction of
      plasma epinephrine levels in the first 15 min, which was followed by a
      significant increase that remained high up to 120 min after injection.
      Norepinephrine levels increased immediately after injections and remained high
      from 30 until 120 min. To test the effect of formalin injection in a stressful
      condition, we exposed animals to 2 h immobilization stress. In the first
      experiment, formalin was injected before the start of immobilization. A
      significant decrease of plasma epinephrine levels was measured up to 25 min post
      injection, whereas plasma norepinephrine levels remained high. A second formalin
      injection during immobilization was as effective as the first one: It depleted
      plasma epinephrine levels from 5 to 15 min post-injection without significant
      changes in norepinephrine levels. In the second experiment, formalin given after
      the beginning of immobilization produced a significant decrease of epinephrine
      levels 15 min after the injection and produced a significant increase 60 min
      after injection. The plasma norepinephrine levels were significantly increased by
      40 min post-injection. The data show that the inhibitory process during the
      interphase of formalin test is able to significantly decrease epinephrine release
      not only during basal conditions but also during exposure to a severe stressor,
      such as immobilization without suppression of plasma norepinephrine levels.

PMID- 15240359
TI  - Different effects of novel stressors on sympathoadrenal system activation in rats
      exposed to long-term immobilization.
AB  - Activation of the sympathoadrenal system, evaluated by plasma levels of
      epinephrine (E) and norepinephrine (NE) after exposure of rats to various
      stressors, is well documented. However, response of rats exposed long-term to a
      homotypic stressor and then exposed once to a heterotypic novel stressor is
      poorly understood. In the present study, we examined changes in plasma levels of
      catecholamines (CA) and corticosterone (COR) of rats after a single (2-h) or long
      term repeated immobilization (41 times, 2 h daily) and in rats adapted to long
      term immobilization exposed once to the novel stress of cold exposure or insulin
      or 2-deoxy-D-glucose (2DG) administration. Long-term immobilization produced a
      significant elevation of basal plasma COR but not NE and E levels. Long-term
      immobilized rats exposed to insulin or 2DG showed significant elevation of plasma
      CA and COR levels in comparison to the administration to control rats. Exposure
      of long-term immobilized and control rats to cold stress increased plasma NE and
      COR, whereas plasma E was not significantly changed. The exposure of long-term
      immobilized rats to a further single immobilization (2 h) increased plasma CA
      levels, but, in naive control rats, the single immobilization produced more
      pronounced increases. These data suggest that rats exposed to homotypic long-term
      immobilization are able to respond to heterotypic stressors by higher activation
      of the sympathoadrenal system as compared with the control, previously unstressed
      rats. Reduced plasma CA levels in long-term immobilized rats exposed to homotypic
      stressor are most probably due to an adaptation at the level of brain regulatory
      centers.

PMID- 15240360
TI  - Immobilization stress-induced increase in plasma catecholamine levels is
      inhibited by a prolactoliberin (salsolinol) administration.
AB  - Catecholamines (CAs) are significantly involved in the regulation of homeostasis
      of the organism at rest and especially during stressful situations. Stress
      induces increases in plasma CA (epinephrine and norepinephrine) levels and
      prolactin (PRL) release from the adenopituitary. We have recently observed that
      salsolinol, which is produced by the neuro-intermediate lobe of the pituitary
      gland and by the hypothalamus, can selectively release PRL. Salsolinol is
      therefore considered to be a putative endogenous PRL-releasing factor. Based on
      the similarity of CA and PRL responses to stressors, we investigated whether
      salsolinol plays a role in the regulation of plasma CA levels at rest and of CA
      release induced by immobilization stress (IMO). Salsolinol did not affect CA
      baseline levels; however, it did inhibit IMO-induced CA release. Thus, the
      present study shows for the first time that salsolinol is not only a PRL
      releasing factor but is also a potent inhibitor of stress-induced release of
      epinephrine and norepinephrine.

PMID- 15240361
TI  - Angiotensin II AT1 receptor blockade prolongs the lifespan of spontaneously
      hypertensive rats and reduces stress-induced release of catecholamines,
      glucocorticoids, and vasopressin.
AB  - A 2-week pretreatment with an Angiotensin II AT(1) antagonist prevented the
      adrenomedullary and hormonal response to isolation stress. We studied the effect
      of life-long treatment with the AT(1) receptor antagonist candesartan, 10
      mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of
      age on the response to stress of stress-sensitive spontaneously hypertensive rats
      (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were
      submitted to 24-h isolation stress at different times during the treatment.
      Treatment with candesartan extended the lifespan of SHRs. AT(1) receptor blockade
      retained its capacity to blunt the response to isolation stress over a long
      period of treatment. The AT(1) antagonist inhibited epinephrine release in SHR
      but not in WKY rats during the first 3 months, corticosterone release in SHR and
      WKY rats during 10 months, and vasopressin release in SHR rats during 18 months
      of treatment when rats were submitted to isolation stress. There were no changes
      in vasopressin release in WKY rats during stress or after AT(1) receptor
      blockade. We conclude that the blockade of the stress response by the AT(1)
      receptor antagonist is long lasting and differs between stress-prone SHR and WKY
      rats and that the specific components of the stress response (sympathoadrenal
      activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin
      release) react differently to AT(1) receptor blockade. The long-term protective
      effects of AT(1) receptor blockade can be important in animals vulnerable to
      stress and, in conjunction with the normalization of blood pressure, can prolong
      lifespan through end-organ protection.

PMID- 15240362
TI  - Fight or flight, forbearance and fortitude: the spectrum of actions of the
      catecholamines and their cousins.
AB  - Catecholamines are recognized to play an important part in the fight-or-flight
      response to impending stress. Catecholamine and other phase-reactant levels are
      raised in the first 24 h following acute stress, but the bigger picture of their
      action on the organism is unavailable. In this article, we examine their actions
      in light of the theory of phase transitions borrowed from the numerate sciences.
      Phase transitions involve changes in the state of matter or an organism with a
      common example of what is termed a first-order phase transition (sudden change)
      being provided by the popular expression "the straw that broke the camel's back."
      We propose that the response to catecholamines follows a triphasic response: a
      Phase I response is the fight-or-flight response to impending stress that
      protects the animal. With mild to intermediate stress, the Phase II or
      forbearance response allows it to tolerate the physiological upset. With severe
      stress, however, severe vital organ vasoconstriction leads to a quick death. The
      present theory has value in understanding the clinical picture in acute stress.
      Phase II or Forbearance Phase corresponds to Classes I, II, and III of
      hemorrhagic shock, and Phase III or Fortitude Phase to Class IV. Thus, a Phase
      III or fortitude response is to the animal what apoptosis is to the individual
      cell and has social implications. The present framework provides a fresh
      perspective on the action of the catecholamines and their cousins.

PMID- 15240363
TI  - Chronic stress-induced effects of corticosterone on brain: direct and indirect.
AB  - Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing
      factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their
      actions in brain and anterior pituitary (canonical feedback). With chronic
      stress, glucocorticoid feedback inhibition of ACTH secretion changes markedly.
      Chronically stressed rats characteristically exhibit facilitated ACTH responses
      to acute, novel stressors. Moreover, in adrenalectomized rats in which
      corticosterone was replaced, steroid concentrations in the higher range are
      required for facilitation of ACTH responses to occur after chronic stress or
      diabetes. Infusion of corticosterone intracerebroventricularly into
      adrenalectomized rats increases basal ACTH, tends to increase CRF, and allows
      facilitation of ACTH responses to repeated restraint. Therefore, with chronic
      stressors, corticosterone seems to act in brain in an excitatory rather than an
      inhibitory fashion. We believe, under conditions of chronic stress, that there is
      an indirect glucocorticoid feedback that is mediated through the effects of the
      steroid +/- insulin on metabolism. Increased energy stores feedback on brain to
      inhibit hypothalamic CRF and decrease the expression of dopamine-beta-hydroxylase
      in the locus coeruleus. These changes would be expected to decrease the level of
      discomfort and anxiety induced by chronic stress. Moreover, central neural
      actions of glucocorticoids abet the peripheral effects of the steroids by
      increasing the salience and ingestion of pleasurable foods.

PMID- 15240364
TI  - The role of vasopressin in hypothalamo-pituitary-adrenal axis activation during
      stress: an assessment of the evidence.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is a key component of the stress
      reaction. Most contemporary reviews mention the corticotropin-releasing hormone
      and arginine vasopressin (AVP)-containing parvocellular neurons of the
      hypothalamic paraventricular nucleus as the endocrinomotor component of the
      system. Although there are many studies about the role of AVP in the stress
      activation, there is evidence consistent and inconsistent with the general view
      on the importance of AVP. We propose a list of experiments that may provide
      critical evidence for or against the widely held opinion. The naturally AVP
      deficient Brattleboro rat seems to be a good tool for studying the role of AVP.
      Our experiments on Brattleboro rats with restraint and ip hypertonic saline
      injection did not support the prominent role of AVP in acute stress, although in
      forced swim the lack of AVP influenced the HPA axis activation. Among different
      chronic stress situations (14 days' restraint, chronic morphine or ip hypertonic
      saline treatment, streptozotocin-induced diabetes mellitus), the role of AVP was
      not confirmed by changes in somatic parameter (i.e., body, thymus, and adrenal
      weight changes).

PMID- 15240365
TI  - Long-term effects of a single exposure to immobilization on the hypothalamic
      pituitary-adrenal axis: neurobiologic mechanisms.
AB  - In apparent contrast to previous results from other labs, we have found that a
      single exposure to a severe stressor such as immobilization (IMO) caused a long
      term desensitization of the hypothalamic-pituitary-adrenal (HPA) response to the
      homotypic stressor. Because such HPA desensitization was not found in response to
      heterotypic stressors, it seemed at first that we were describing a habituation
      process already observed after a single experience with the stressor. However, a
      more detailed analysis revealed two main properties incompatible with the
      interpretation of the results in terms of habituation: (1) The intensity of
      desensitization increases over the course of days to weeks with no additional
      exposures to the stressor, and (2) the degree of desensitization was greater with
      more severe stressors. The long-term effects were also observed after a single
      exposure to a high dose of a systemic stressor such as endotoxin but not after
      insulin-induced hypoglycemia, suggesting that not all severe systemic stressors
      can induce such long-term desensitization. Because systemic stressors are known
      to be processed in specific brain areas and because we have found changes in c
      fos mRNA response to the homotypic stressor in some brain areas as a consequence
      of previous experience with IMO, we hypothesize that some severe stressors do not
      induce long-term desensitization because they are not processed in brain areas
      sensitive to previous experience with the stressor. The neurochemical mechanisms
      involved in the induction of long-term effects on the HPA axis are in process,
      but our results suggest only a partial role of glucocorticoids and NMDA
      receptors.

PMID- 15240366
TI  - Alcohol alters rat adrenomedullary function and stress response.
AB  - Most alcohol researchers do not address the effects of intoxication on the
      sympatho-adrenomedullary system response to stressful situations. We previously
      determined that rats consuming nearly 9 g ethanol (EtOH) per kg body weight per
      day in liquid diet form for 1 week increased adrenal gene expression of enzymes
      for catecholamine synthesis that was further elevated by acute IMMO. We
      hypothesized that the response to chronic mild stressors would also be altered
      after consumption of lower concentrations of EtOH in drinking water. Two
      experiments were conducted: 10% w/v for 4 weeks or 6% w/v for 7 weeks +/- wire
      mesh restraint (WMR). These were compared with ad libitum (adlib) and pair-fed
      control rats. Adrenal gene expression of catecholamine synthesizing enzymes was
      assayed. Tyrosine hydroxylase gene expression was elevated 80% to 90% by alcohol
      consumption in both experiments (P < 0.001) compared with adlib control rats.
      Dopamine betab-hydroxylase and phenylethanolamine-N-methyl transferase gene
      expressions were unaffected by 10% alcohol (P > 0.05) but were increased by 6%
      alcohol (P < 0.01). WMR decreased already elevated gene expression of all three
      enzymes. Pair feeding to 6% EtOH drinkers also increased gene expression for the
      three enzymes but was decreased by WMR, although not to levels of adlib rats.
      Increased gene expression for adrenal synthesis of catecholamines in response to
      repeated alcohol consumption increases the likelihood that the subject can
      respond physiologically to acute or chronic stress. This may have life-saving
      consequences in humans and in animals known to consume fermented materials and
      may contribute to increased aggressive behavior.

PMID- 15240367
TI  - Pivotal role of an endogenous tetrahydroisoquinoline, salsolinol, in stress- and
      suckling-induced release of prolactin.
AB  - In mammals, the role of a prolactin-releasing factor (PRF) in the acute changes
      of prolactin (PRL) secretion that usually occur after challenges (e.g., suckling
      stimulus or stress) of homeostasis has been suspected for a long time. We have
      recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,
      salsolinol (SAL), produced by the hypothalamus and the neuro-intermediate lobe
      (NIL) of the pituitary gland, can selectively release PRL from the anterior lobe
      (AL). Moreover, binding sites for SAL have been detected in areas like median
      eminence, NIL, and AL. It has been proposed that SAL is a putative endogenous
      PRF. We have also found that a structural analogue of SAL, 1-methyl-3,4
      dihydroisoquinoline (1MeDIQ), is able to block dose-dependently SAL-, suckling-,
      and immobilization (IMO) stress-induced release of PRL without having any
      influence on alpha-methyl-p-tyrosine (alphaMpT)-induced PRL responses. Neither
      SAL nor 1MeDIQ has any effect on alpha-melanocyte-stimulating hormone (alphaMSH),
      adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END) and arginine
      vasopressin (AVP) secretion. Moreover, SAL-induced PRL response was attenuated in
      male rats pretreated with dexamethasone (DEX). These results strongly suggest
      that SAL has an important role in the regulation of PRL release induced by
      physiologic and environmental stimuli; therefore, it can be considered as the
      strongest candidate for being the PRF in the hypothalamo-hypophysial system. Our
      findings also indicate that the adrenal steroids may play an inhibitory feedback
      role in SAL-mediated PRL response.

PMID- 15240368
TI  - Glucocorticoids and vulnerability to psychostimulant drugs: toward substrate and
      mechanism.
AB  - Glucocorticoid hormones can modulate the propensity of individuals to develop
      addictive behavior and, by doing so, contribute to the existence of individual
      differences in vulnerability to drugs. This article summarizes recent findings
      that increase our knowledge about drug-induced neuronal adaptations in the brain
      reward system and the role glucocorticoids may play in this process. Evidence
      exists that drugs and stress can induce similar changes in excitatory synaptic
      strength within the mesolimbic dopamine system, suggesting a coordinate mechanism
      for drugs of abuse and glucocorticoids. The glucocorticoid receptor (GR) plays an
      essential role in the stress-induced synaptic alterations, and studies using
      transgenic mice suggest that the GR is a key modulator of the motivation to take
      drugs and of the behavioral effects of repeated drug intake. The current state of
      research into the interplay between glucocorticoid hormones and addiction has
      reached a new phase in which detailed cellular and molecular analyses of the
      actual mechanisms will become possible. An important role is assigned to the GR,
      although many issues remain to be addressed, such as the actual site of
      glucocorticoid action in the brain, the molecular mechanisms and targets of GR
      mediated glucocorticoid effects, and their interaction with genetic background.

PMID- 15240369
TI  - Effect of chronic emotional stress on habituation processes in open field in
      adult rats.
AB  - In our previous study, repeated stress in the neonatal period was found to slow
      habituation in the open field in adult rats. The objective of the present study
      was to investigate how chronic stress can affect habituation processes in the
      open field when occurring in adulthood. Animals were exposed to 1 week of
      immobilization on metal boards followed by 1 week of hypokinesis. After the
      stress procedure, rats were tested in the open field (once daily in 6-min
      sessions for four consecutive days). Immediately after the last open-field test,
      animals were decapitated. The rapidity of between- and within-session habituation
      was lower than in control rats. However, this lowering failed to be statistically
      significant compared with control rats. On the other hand, time latency to step
      down from an elevated platform was significantly increased in stress-exposed
      animals. Four days after the last stressful event, corticotropin-releasing
      hormone mRNA levels in the paraventricular nucleus were significantly increased,
      indicating a long-term activation of the hypothalamic-pituitary-adrenocortical
      axis. The results suggest that, in contrast to neonatal stress exposure, chronic
      emotional stress in adult rats does not represent a risk factor for the
      alteration of habituation processes.

PMID- 15240370
TI  - Effect of immobilization on in vitro thyrotropin-releasing hormone release from
      brain septum in wild-type and corticotropin-releasing hormone knock-out mice.
AB  - There is considerable evidence linking alcohol consumption, sedation, and
      thyrotropin-releasing hormone (TRH) in the brain septum. We have shown that
      ethanol in clinically relevant concentrations can in vitro induce TRH release
      from the septum by a mechanism involving neuronal swelling. Corticotropin
      releasing hormone-deficient (CRH-KO) mice serve as an interesting model to help
      us understand the role of CRH in the regulation of different neuroendocrine
      systems. The aim of this study was to compare TRH release activity in the brain
      septum at basal and stress conditions in CRH-KO mice and their wild-type (WT)
      littermates. Experimental mice were decapitated immediately or 3 h after single
      (2 h) or repeated (seven times for 2 h daily) immobilization stress. The brain
      septum was immediately cut out and incubated to measure basal-, ethanol-, and
      hyposmosis-stimulated TRH release in vitro. Ethanol in isosmotic medium or
      hyposmotic medium stimulated TRH release from mice septal explants from WT and
      CRH-KO mice. The response was disturbed immediately after immobilization and
      recovered 3 h later. Our results show that immobilization stress transiently
      affects the TRH system in brain septum. Inborn absence of CRH does not affect
      septal TRH and its response to ethanol before and 3 h after immobilization.

PMID- 15240371
TI  - Effect of cold exposure on serum DBH and interscapular brown adipose tissue MAO
      activity in hypothyroid T3- and T4-treated rats.
AB  - As the indicators of sympathetic nervous system (SNS) function, the activity of
      serum dopamine-beta-hydroxylase (DBH) and interscapular brown adipose tissue
      (IBAT) monoamine oxidase (MAO) were examined in rats that were chemically
      thyroidectomized (TX), treated with thyroid hormones, and exposed to cold (4
      degrees C). In TX animals, body temperature (bt) significantly decreased, and
      relative IBAT mass increased as compared with control, euthyroid animals,
      independent of the ambient temperature. The bt fall in TX cold-exposed animals
      was more severe, provoking hypothermia after 4 h. Under the same experimental
      conditions, the SNS function was enhanced as judged by the increased serum DBH
      and IBAT MAO activities. The treatment of TX animals with T(4) and T(3) re
      established the temperature (bt was at the level of controls) and sympathetic
      homeostasis (DBH activity was at the level of controls) in animals maintained at
      room temperature but not in those kept under cold conditions. T(4) and T(3) did
      not affect IBAT MAO activity of TX rats: It remained significantly above the
      control values whether the animals were maintained at room temperature or exposed
      to cold. In conclusion, the IBAT of TX cold-exposed rats is incapable of
      responding to the enhanced thermogenic needs despite the increased SNS activity
      and thyroid hormone substitution.

PMID- 15240372
TI  - Stress is associated with inhibition of type I iodothyronine 5'-deiodinase
      activity in rat liver.
AB  - Type I iodothyronine deiodinase (5'-DI) generates the thyromimetically active
      hormone 3,5,3'-triiodothyronine (T(3)) by reductive monodeiodination of the
      phenolic ring of L-thyroxine (T(4)). The present study was undertaken to compare
      the effects of cold stress (4 degrees C) alone or in combination with
      immobilization stress (IMO), insulin treatment (5 IU/kg, i.p.) or 2-deoxy-D
      glucose (2DG)-induced intracellular glucopenia on the activity of 5'-DI in rat
      liver. Cold stress either for 24 h or 28 days when compared to that in the
      nonstressed group of rats significantly reduced (P < 0.001) the activity of 5'-DI
      in liver. In comparison with cold stressed rats for 28 days, an additional
      decrease in 5'-DI activity was observed when those rats underwent 1 x IMO in cold
      for 2 h (P < 0.001) or insulin treatment (P < 0.05). A significant decrease in 5'
      DI activity was found also in rats maintained at room temperature that underwent
      a single 1 x IMO for 2 h (P < 0.001) or insulin treatment (P < 0.01) when
      compared to nonstressed animals. In comparison with nonstressed rats, no
      significant change of the 5'-DI activity was observed after 2DG application (500
      mg/kg, i.p.) at room temperature. In conclusion, cold stress and/or 1 x IMO,
      insulin treatment, or 1 x IMO at room temperature markedly affects reductive
      monodeiodination of T(4), and thus reduces the concentration of biologically
      active T(3) in liver.

PMID- 15240373
TI  - Leaky catecholamine stores: undue waste or a stress response coping mechanism?
AB  - Turnover of catecholamines, representing the constant loss and replenishment of
      neurotransmitter by synthesis, is usually considered to be driven exclusively by
      catecholamine release. This is incorrect. An important contribution of
      intraneuronal metabolism of norepinephrine to turnover, and dependence of this on
      leakage of norepinephrine from vesicular stores, was originally proposed by Kopin
      in 1964. Several years later, Maas and colleagues concluded that at least 75% of
      norepinephrine turnover is due to intraneuronal metabolism without prior release
      at sympathetic nerve endings. More recently it was shown in the resting human
      heart that about 12% of norepinephrine turnover is due to extraneuronal uptake
      and metabolism or loss of the transmitter to the circulation, 15% is due to
      intraneuronal metabolism after reuptake, and 73% is due to intraneuronal
      metabolism of norepinephrine leaking from storage vesicles. Thus, contrary to
      usual depictions, vesicular stores of catecholamines do not exist in a static
      state simply waiting for exocytotic release. Rather, these stores exist in a
      highly dynamic equilibrium with the surrounding cytoplasm, with passive outward
      leakage of amines counterbalanced by inward active transport under the control of
      vesicular monoamine transporters. The large contribution of leakage to
      catecholamine turnover may seem inconsistent with cellular economy. In fact, this
      contribution provides an important mechanism for "gearing down" the requirement
      for increases in catecholamine synthesis to match increases in catecholamine
      release, and thereby provides sympathetic nerves with a capacity for a more
      extended range of sustainable release rates in response to stress than would
      otherwise be possible.

PMID- 15240374
TI  - Functional neuroimaging of sympathetic innervation of the heart.
AB  - Many concepts about acute and chronic effects of stress depend on alterations in
      sympathetic nerves supplying the heart. Physiologic, pharmacologic, and
      neurochemical approaches have been used to evaluate cardiac sympathetic function.
      This article describes a fourth approach that is based on nuclear scanning to
      visualize cardiac sympathetic innervation and function and relationships between
      the neuroimaging findings and those from other approaches. Multiple-system
      atrophy with orthostatic hypotension (formerly the Shy-Drager syndrome) features
      normal cardiac sympathetic innervation and normal entry of norepinephrine into
      the coronary sinus (cardiac norepinephrine spillover), in contrast to Parkinson
      disease with orthostatic hypotension, which features neuroimaging and
      neurochemical evidence for loss of cardiac sympathetic nerves. This difference
      may have important implications not only for diagnosis but also for understanding
      the etiology of Parkinson disease. By analysis of curves relating myocardial
      radioactivity with time (time-activity curves) after injection of a
      sympathoneural imaging agent, it is possible to obtain information about cardiac
      sympathetic function. Abnormal time-activity curves are seen in common disorders
      such as heart failure and diabetic neuropathy and provide an independent, adverse
      prognostic index. Analogous abnormalities might help explain increased
      cardiovascular risk in psychiatric disorders such as melancholic depression.

PMID- 15240375
TI  - Subcellular compartmentation of neuronal protein synthesis: new insights into the
      biology of the neuron.
AB  - During the past few years, it has become well established that the distal
      structural/functional domains of the neuron contain numerous mRNAs. However,
      there is a paucity of information on the composition and function of these unique
      mRNA populations. In this article, we review recent evidence to support the
      hypothesis that protein synthesis occurs in multiple subcellular compartments in
      the neuron, to include the axon and presynaptic nerve terminal. The studies we
      describe use the squid giant axon and photoreceptor neuron as model invertebrate
      motor and sensory systems, respectively. Initial cell-free translation studies
      and molecular hybridization analysis established that the giant axon contained a
      heterogeneous population of polyadenylated mRNAs. The application of differential
      mRNA display methodology greatly facilitated the isolation and identification of
      29 of these mRNAs, which encode cytoskeletal proteins, molecular motors,
      translation factors, various nuclear-encoded mitochondrial mRNAs, and several
      novel mRNA species. RT-PCR analysis of RNA from squid brain synaptosomes
      confirmed the presence of these mRNAs in the presynaptic nerve terminal. The
      presence of these mRNAs in polysomes purified from the synaptosomal fraction
      establish that these messengers are actively translated in the terminal. Results
      of in vitro labeling studies demonstrate that a significant fraction of the
      nuclear-encoded mitochondrial protein derives from the local synthesis in the
      terminal. This finding calls attention to the intimacy of the relationship that
      has evolved between the nerve terminal and its energy-generating system. The role
      that local protein synthesis might play in the mammalian nervous system and in
      the neuronal response to stress is discussed.

PMID- 15240376
TI  - Basal and stress-induced differences in HPA axis, 5-HT responsiveness, and
      hippocampal cell proliferation in two mouse lines.
AB  - To characterize individual differences in neuroendocrine and neurochemical
      correlates of stress coping, two lines of wild house mice were studied. These
      mice are genetically selected for high and low aggression and show distinctly
      different behavioral strategies toward environmental stimuli. Long attack latency
      (LAL), low aggressive mice display a passive coping style, whereas short attack
      latency (SAL), high aggressive mice show an active coping style. It was
      hypothesized that this difference in behavioral coping style is associated with
      differences in stress system reactivity. This was tested by investigating the
      regulation of the hypothalamus-pituitary-adrenal (HPA) axis and the serotonin (5
      HT) system and hippocampal cell proliferation rate in these mice under baseline
      and stress conditions. Baseline corticosterone output in LAL mice was found to be
      more sensitive to adrenocorticotropic hormone, but showed less day/night
      variation than in SAL mice. Furthermore, LAL mice showed lower hippocampal 5
      HT(1A) receptor gene expression and function. Basal hippocampal cell
      proliferation rate was slightly lower in LAL than in SAL mice. Exposure to acute
      stress (forced swimming for 5 min) resulted in a hyper-reactive HPA response, a
      reduced increase in brain 5-HT metabolism, and an almost 50% reduction in
      hippocampal cell proliferation rate in LAL compared with SAL mice. Chronic
      psychosocial stress (sensory contact stress) induced long-lasting changes in the
      HPA axis in LAL, but not in SAL mice. In conclusion, these studies show that a
      genetic trait in behavioral coping style in wild house mice is associated with
      differences in HPA regulation, 5-HT neurotransmission, and hippocampal cell
      proliferation rate. The results further indicate that LAL mice have a higher
      stress responsivity than SAL mice. These results may have implications for a
      differential susceptibility for stress-related mood disorders.

PMID- 15240377
TI  - Repeated stress-induced stimulation of catecholamine response is not followed by
      altered immune cell redistribution.
AB  - Stress response is considered an important factor in the modulation of immune
      function. Neuroendocrine hormones, including catecholamines, affect the process
      of immune cell redistribution, important for cell-mediated immunity. This
      longitudinal investigation was aimed at evaluating the effect of repeated stress
      induced elevation of catecholamines on immune cell redistribution and expression
      of adhesive molecules. We assessed the responses of epinephrine (EPI),
      norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and
      percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill
      exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise
      was performed before and after 6 weeks of endurance training consisting of a 1-h
      run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males.
      We did not observe any significant changes in the basal levels of EPI, NE, and
      cortisol in the plasma, nor in the immune parameters after ET and HDBR. The
      exercise test led to a significant (P <.001) elevation of EPI and NE levels after
      both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an
      increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+,
      CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+
      lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We
      found comparable changes in all measured immune parameters after ET and HDBR. In
      conclusion, repeated stress-induced elevation of EPI and NE was not associated
      with an alteration in immune cell redistribution found in response to the single
      bout of exercise.

PMID- 15240378
TI  - Enriched environment influences adrenocortical response to immune challenge and
      glutamate receptor gene expression in rat hippocampus.
AB  - Housing of animals in an enriched environment (EE) has many positive effects on
      brain structure and function and can facilitate recovery from various brain
      injuries. The purpose of this study was to evaluate whether enriched rearing
      could alter the stress response induced by repeated immune challenge and to
      investigate the influence of EE and immune challenge on glutamate receptor gene
      expression in the hippocampus. Male 2-mo-old Wistar rats were kept under standard
      conditions (SC) or in an EE for 5 weeks. Immune challenge was performed by
      Escherichia coli lipopolysaccharide (LPS) injected repeatedly (ip) in increasing
      doses (10, 20, and 40 microg/kg/mL) once daily for five consecutive days. The
      animals were decapitated 2 h after the last injection. Blood samples, adrenals,
      and hippocampi were collected. LPS induced an increase in plasma and adrenal
      levels of corticosterone and a transient decrease in body weight of animals kept
      under SC, but not in an EE. Enriched housing resulted in an increase in adrenal
      weights and enhanced gene expression of hippocampal AMPA GluR1 receptor subunit.
      Concerning the LPS treatment, no effects on adrenal and thymus weights and
      glutamate receptor mRNA levels in the hippocampus were noticed. Thus,
      vulnerability to some negative effects of repeated immune challenge may be
      modified by environmental conditions associated with changes in brain plasticity.
      The fact that differences in housing conditions change stress response has to be
      considered in biomedical research.

PMID- 15240379
TI  - Prenatal immune challenge affects growth, behavior, and brain dopamine in
      offspring.
AB  - It is known that the development and plasticity of the neuroendocrine system can
      be affected by many factors, and that adverse events during the prenatal period
      can result in long-lasting changes in adulthood. This study was aimed at
      evaluating the possible consequences for offspring from chronic inflammation
      during pregnancy. Chronic inflammation was simulated by treatment with increasing
      doses of lipopolysaccharide (LPS) to dams on days 15 through 19 of pregnancy.
      Attempts were made to prevent possible negative alterations by keeping animals in
      an enriched environment (EE). Maternal exposure to LPS resulted in a significant
      reduction of body weight of male offspring during the weaning period. This
      difference remained until the age of 63 days in controls (C), but not in animals
      reared in EE. The content of dopamine in the nucleus accumbens was found to be
      lower in prenatally stressed (PS) adult males. Furthermore, prenatal exposure to
      maternal immune challenge was associated with lower locomotor activity in
      elevated plus maze and increased number of skips in the beam-walking test, as
      observed in female offspring. No differences in ACTH and corticosterone
      concentrations with regard to prenatal treatment were found; however, both groups
      kept in EE showed increased levels of corticosterone as well as enlarged adrenal
      glands. Thus, immune activation during pregnancy may induce long-term changes in
      brain catecholamines and behavior, but it is not harmful to basal hormone
      secretion in the offspring.

PMID- 15240380
TI  - Mechanisms underlying the gastroprotective action of glucocorticoids released in
      response to ulcerogenic stress factors.
AB  - Our previous results demonstrate the gastroprotective but not ulcerogenic action
      of glucocorticoids released in response to ulcerogenic stress factors. The
      present study was undertaken to investigate the possible mechanisms underlying
      the gastroprotective action of glucocorticoids in rat stomachs. The effects of
      deficiency of glucocorticoid production, with or without corticosterone
      supplementation, on blood flow velocity in gastric microvessels, microvascular
      permeability, mucus production, motility as well as gastric lesions were studied
      3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or
      indomethacin administration. The contribution of glucocorticoids in the healing
      process of gastric injury was also evaluated. The deficiency in glucocorticoid
      production significantly potentiated the functional disorders induced by
      ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus
      production and an increase in gastric motility and in microvascular permeability,
      which resulted in aggravation of the formation of gastric lesions as well as
      impairment of their healing. The changes observed were prevented by
      supplementation of corticosterone at a dose mimicking a stress-induced
      corticosterone rise. We conclude that a gastroprotective action of
      glucocorticoids may be provided by multiple actions, including maintenance of the
      gastric mucosal blood flow and mucus production, attenuation of the enhanced
      gastric motility and microvascular permeability as well as beneficial influences
      on healing processes.

PMID- 15240381
TI  - Regulation of vasopressin V1b receptors and stress adaptation.
AB  - Vasopressin (VP) regulates pituitary corticotroph function by acting upon plasma
      membrane G-protein receptors of the V1b subtype (V1bR), coupled to calcium
      phospholipid signaling. The number of these receptors in the anterior pituitary
      varies during stress in direct correlation with corticotroph responsiveness,
      suggesting that the V1bR plays an important role during adaptation of the
      hypothalamic-pituitary-adrenal (HPA) axis to stress. The molecular regulation of
      pituitary V1bR involves transcriptional and translational mechanisms. V1bR gene
      transcription, which is necessary to maintain V1bR mRNA levels, depends on a
      number of responsive elements in the promoter region, of which the stretch of GA
      repeats near the transcription start point (GAGA box) is essential. Although
      transcriptional activation is necessary to maintain V1bR mRNA levels, the lack of
      correlation between VP binding and V1bR mRNA suggests that V1bR content is mainly
      regulated at the translational level. Two potential mechanisms by which the 5'
      untranslated region (5'UTR) of the V1bR mediates negative and positive regulation
      of V1bR translation were identified. This includes the repressor effect of small
      open reading frames (ORF) present upstream of the main V1bR ORF, and an internal
      ribosome entry site (IRES), which activates V1bR translation. The existence of
      multiple loci of regulation for the V1bR at transcriptional and translational
      levels provides a mechanism to facilitate plasticity of regulation of the number
      of pituitary vasopressin receptors according to physiological demand.

PMID- 15240382
TI  - Angiotensin II AT1 and AT2 receptor types regulate basal and stress-induced
      adrenomedullary catecholamine production through transcriptional regulation of
      tyrosine hydroxylase.
AB  - The sympathoadrenal response to stress includes a profound increase in
      adrenomedullary catecholamine synthesis driven by stimulation of tyrosine
      hydroxylase (TH) transcription. We studied the role of Angiotensin II type 1 and
      2 (AT(1) and AT(2)) receptors during isolation stress, and under basal
      conditions. Pretreatment of rats with the AT(1) receptor antagonist candesartan
      for 14 days prior to isolation completely prevented the stress-induced
      stimulation of catecholamine synthesis, decreasing tyrosine hydroxylase
      transcription by preventing the expression of the transcriptional factor, Fos
      related antigen 2 (Fra-2). In addition, AT(1) receptor antagonism prevented the
      stress-induced increase in adrenomedullary AT(2) receptor binding and protein.
      Treatment of non-stressed, grouped animals under basal conditions with the AT(1)
      receptor or with PD 123319, an AT(2) receptor antagonist, decreased the
      adrenomedullary norepinephrine (NE) content and TH transcription. While AT(1)
      receptor antagonism decreased the levels of Fra-2 and the phosphorylated forms of
      cAMP responsive element binding protein (pCREB) and EKR2 (p-ERK2, phosphor-p42
      MAP kinase), the AT(2) antagonist decreased Fra-2 with no change in the
      phosphorylation of CREB or EKR2. Our results demonstrate that both
      adrenomedullary AT(1) and AT(2) receptor types maintain and promote the
      adrenomedullary catecholamine synthesis and the transcriptional regulation of TH.
      Instead of opposing effects, however, our results indicate a complex synergistic
      regulation between the AT(1) and AT(2) receptor types.

PMID- 15240383
TI  - Inositol 1,4,5-trisphosphate receptors in the heart compared to other tissues are
      differently modulated by stress.
AB  - IP(3) receptors are intracellular calcium channels, releasing calcium from the
      sarcoplasmic reticulum. In the heart, IP(3) receptors of type 1 and 2 were found.
      These receptors predominate in atria, although they occur also in ventricles, as
      determined by real-time PCR and Western blot analysis. Single-immobilization
      stress was found to increase mRNA and/or protein levels of types 1 and 2 IP(3)
      receptors in cardiac atria. However, in stellate ganglia, which innervate the
      heart, no changes in the mRNA of the type 1 IP(3) receptors were observed after
      single-immobilization stress. In adrenal medulla, a moderate decrease in both
      mRNA and protein levels of IP(3) receptors was observed after single
      immobilization exposure. After repeated immobilization, mRNA and protein levels
      of types 1 and 2 IP(3) receptors decreased significantly in all tested tissues.
      Our results point to different processing of the single stress in different
      tissues, while repeated stress results in rapid and significant decrease of the
      IP(3) receptors.

PMID- 15240384
TI  - The effects of short-term immobilization stress on muscarinic receptors, beta
      adrenoceptors, and adenylyl cyclase in different heart regions.
AB  - Heart muscarinic receptors (MR) and beta-adrenoceptors (BAR) belong to a large
      family of G-protein-coupled receptors. Although the role of catecholamines in the
      stress has been under keen investigation for many years, the effects of
      immobilization on this pair of receptors, considering their almost completely
      opposite actions in the heart, are not yet known. We have studied the effects of
      short-term immobilization (for 120 min) with different times of decapitation
      after the end of the immobilization period (0, 3, and 24 h) on MR, BAR (beta(1)
      AR and beta(2)-AR using radioligand binding studies), and adenylyl cyclase (AC;
      using high-pressure liquid chromatography detection of cAMP) in different heart
      regions (left and right atria with or without cardiac ganglion cells [auriculae],
      septum, and left and right ventricles). The effects of one immobilization period
      were first apparent after 24 h. Stress brought about a downregulation of MR and
      BAR with decrease in AC activity. These effects were regionally specific and were
      predominantly expressed in the right atria, which is rich in ganglia cells, and
      in the right ventricles. Our results indicate that stressful stimuli can
      influence not only BAR, but MR, and that AC activity can also be affected. This
      finding is in good agreement with our previous hypothesis that parallel changes
      are possible in the number of this pair of receptors on cell membranes.

PMID- 15240385
TI  - Spatial performance and corticosteroid receptor status in the 21-day restraint
      stress paradigm.
AB  - Twenty-one days of restraint stress has been shown to affect hippocampal
      plasticity, neurogenesis, and spatial memory. Hippocampal glucocorticoid
      receptors (GR) and mineralocorticoid receptors (MR) are the main mediators of
      stress response and learning/memory processes. We studied the performance of male
      and female rats on a hippocampal-dependent spatial task after 21 days of
      restraint in relation to the stress-induced changes of GR and MR status in their
      hippocampi. Reduced GR immunostaining was detected in the dentate gyrus and CA1
      area of stressed male rats. Stressed male rats performed worse than the male
      control rats on the Morris water maze. In contrast, unaltered (in the dentate
      gyrus) or increased (in CA1) GR immunoreactivity was seen in the hippocampus of
      stressed female rats. Stressed female rats had an improved memory score in the
      task compared with the female control rats. In addition, stressed female rats
      showed increased MR immunostaining in the CA3 area, which is known to be severely
      affected by stress. The observed sexually dimorphic effects of 21-day restraint
      in spatial learning and memory may be associated with the sex-dependent changes
      in hippocampal corticosteroid receptor status after stress.

PMID- 15240386
TI  - Glucocorticoid receptor and Beta-adrenoceptor expression in epididymal adipose
      tissue from stressed rats.
AB  - Adipocytes isolated from epididymal adipose tissue of foot-shock stressed rats
      are supersensitive to isoprenaline and subsensitive to norepinephrine. These
      alterations are probably mediated by a stress-induced increase in plasma
      corticosterone levels. We investigated whether foot-shock stress modifies the
      expression of glucocorticoid receptors (GRs) and beta-adrenergic protein
      receptors (beta-ARs) in epididymal adipose tissue from rats submitted to one
      daily foot-shock session on three consecutive days. This stress protocol caused
      decreases in GR, beta(1)-AR, and beta(3)-AR protein levels, but caused an
      increase in beta(2)-AR. These results confirm and support previous functional
      studies. The alterations in protein expression may be modulated by the high
      corticosterone levels that downregulate the glucocorticoid receptor.

PMID- 15240387
TI  - 5-HT1A receptor activation before acute stress counteracted the induced long-term
      behavioral effects.
AB  - The long-term behavioral consequences of acute immobilization (IMMO) in rats and
      the effects of 5-HT(1A) receptor activation (8-OH-DPAT: 0.3 mg/kg, sc) were
      studied. Corticosterone levels after IMMO with previous 8-OH-DPAT treatment were
      also studied. Twenty-four hours after IMMO (3 h), rats performed conditioned
      (passive avoidance) and unconditioned (escape behavior) anxiety tests in the
      elevated T maze. Pre-exposure to IMMO induces long-term behavioral changes in
      contrast with control rats. These behavioral alterations include an increase of
      anxiogenic responses, such as exploratory behavior and passive avoidance
      response. This effect was counteracted by 8-OH-DPAT pretreatment and reversed by
      WAY-100635 when administered before 8-OH-DPAT. Serum corticosterone levels
      increased during the first hour of stress and after 8-OH-DPAT administration. Our
      results support the hypothesis that involvement of acute stress is crucial in the
      anxiety-like behaviors and in the potentiation of fear. The activation of 5
      HT(1A) receptors counteracted the long-term effects induced by IMMO.

PMID- 15240388
TI  - Repeated immobilization stress decreases mRNA and protein levels of the type 1
      IP3 receptor in rat heart.
AB  - Stress is one of the major contributors to the development of cardiovascular
      disorders and psychiatric illnesses. Immobilization stress belongs to severe
      stressors and is known to activate several calcium transport systems. The aim of
      this work was to determine whether repeated immobilization stress changes mRNA
      and protein levels of the type 1 and 2 inositol-1,4,5-trisphosphate (IP(3))
      receptors in cardiac tissue. Rats were immobilized for 7 days, 2 h daily. After
      repeated immobilization, increased numbers of collagen fibers were accumulated in
      the heart atria compared to hearts of the control group of rats. Gene expression
      was determined after reverse transcription and subsequent real-time polymerase
      chain reaction, using SYBR Green fluorescent dye. Protein levels were determined
      by Western blot and hybridization with the primary antibody against IP(3)
      receptors. Contrary to single immobilization, repeated immobilization decreased a
      gene expression of the type 1 and 2 IP(3) receptors, and also protein levels of
      the IP(3) receptors. Although the physiologic relevance of our observations
      remains to be elucidated, we propose that the decrease in IP(3) receptors may
      have an impact on the development of the pathophysiologic changes in the heart.

PMID- 15240389
TI  - Angiotensin II AT1 receptor blockade decreases brain artery inflammation in a
      stress-prone rat strain.
AB  - The spontaneously hypertensive rats (SHR) are a genetically hypertensive strain
      with vulnerability to brain ischemia and stress. In SHR, the brain Angiotensin II
      (Ang II) system is chronically stimulated, resulting in brain artery remodeling
      and inflammation. Pretreatment with Ang II AT(1) receptor antagonists protects
      from brain ischemia and prevents the hormonal and sympathoadrenal response to
      stress. In addition, the anti-inflammatory effects of AT(1) receptor antagonists
      are partially responsible for preventing the development of stress-induced
      gastric ulcers. We asked whether AT(1) receptor antagonists could exert anti
      inflammatory effects in the brain vasculature as a mechanism for their protective
      effects against ischemia. As determined by immunohistochemistry, long-term
      inhibition of brain AT(1) receptors by peripheral administration of the AT(1)
      receptor antagonist candesartan (0.3 mg/kg/day for 28 days) normalized the
      pathologic remodeling, decreased expression of the intercellular adhesion
      molecule-1 and the number of associated macrophages, and normalized the
      endothelial nitric oxide synthase expression in cerebral vessels of SHR. The anti
      inflammatory effects of AT(1) receptor antagonists may be an important mechanism
      for protection against ischemia and could participate in the anti-stress
      properties of this class of compounds.

PMID- 15240390
TI  - Angiotensin II AT1 receptor blockade prevents gastric ulcers during cold
      restraint stress.
AB  - Cold-restraint stress reduces gastric blood flow and produces acute gastric
      ulcers. We studied the role of Angiotensin II (Ang II) on gastric blood flow and
      gastric ulceration during stress. Spontaneously hypertensive rats, a stress
      sensitive strain, were pretreated for 14 days with the AT(1) receptor antagonist
      candesartan before cold-restraint stress. AT(1) blockade increased gastric blood
      flow 40% to 50%; prevented gastric ulcer formation by 70% to 80%; reduced the
      increase in adrenomedullary epinephrine and TH mRNA without preventing the stress
      induced increase in adrenal corticosterone; decreased the stress-induced
      expression of tumor necrosis factor alpha (TNF-alpha) and adhesion protein ICAM-1
      in arterial endothelium, and neutrophil infiltration in the gastric mucosa; and
      decreased PGE(2) content. AT(1) receptor blockers prevent stress-induced
      ulcerations by a combination of gastric blood flow protection, decreased
      sympathoadrenal activation, anti-inflammatory effects with reduction in TNF
      alpha, and ICAM-1 expression, leading to reduced neutrophil infiltration while
      maintaining the protective glucocorticoid effects and PGE(2) release. Ang II has
      a crucial role, through stimulation of AT(1) receptors, in the production and
      progression of stress-induced gastric injury, and AT(1) receptor antagonists
      could be of therapeutic benefit.

PMID- 15240391
TI  - Quantitative evaluation of catecholamine enzymes gene expression in adrenal
      medulla and sympathetic Ganglia of stressed rats.
AB  - Stress-induced changes in mRNA levels of tyrosine hydroxylase (TH), dopamine-beta
      hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) have been
      expressed as relative arbitrary units compared with a control group. The aim of
      this study was to quantify basal and stress-induced levels of TH, DBH, and PNMT
      mRNAs in rat adrenal medulla (AM) and stellate ganglia (SG) by the RT-competitive
      PCR method using corresponding competitors of known concentration. In rats
      stressed by immobilization (IMO) once for 2 h, the concentration of mRNAs was
      determined in various intervals after the end of stress stimulus. In SG, the
      basal concentration of TH mRNA was 0.017 amol/ng of total RNA, which is
      approximately 30 times lower than in the AM (0.460 amol/ng RNA). The basal
      concentration of DBH mRNA in SG was 2.60 amol/ng of total RNA, which is about 150
      times more than TH mRNA in SG but only two times less than DBH mRNA in the AM in
      which PNMT mRNA is present in the highest concentration. After a single 2-h IMO,
      the peak elevation of TH and DBH mRNA concentration in SG occurred 24 h after the
      termination of stress stimulus, when their AM mRNA concentrations were already at
      control values. Presence of PNMT mRNA levels in the SG, of control and stressed
      rats has been demonstrated for the first time. Repeated IMO (7 days, 2 h daily)
      did not produce further increase in the mRNA concentrations compared with the
      elevated values found in adapted control groups. Levels of TH protein were
      significantly increased only after repeated IMO in SG and AM. Thus, our data show
      for the first time the exact concentrations of TH, DBH, and PNMT mRNA in SG and
      AM of rats under control and stress conditions. The lowest concentration of TH
      mRNA in the AM and SG supports the hypothesis that tyrosine hydroxylation is the
      rate-limiting step in catecholamine biosynthesis.

PMID- 15240393
TI  - Changes in the concentrations of tetrahydrobiopterin, the cofactor of tyrosine
      hydroxylase, in blood under physical stress and in depression.
AB  - This paper studies changes in the concentrations of tetrahydrobiopterin (BH4),
      the cofactor of tyrosine hydroxylase, in blood under physical stress and in
      depression. BH4 was found to be transiently released from the sympathetic nerves
      under severe physical stress but continuously released in depression with an
      increased oxidation rate of BH4 to B.

PMID- 15240392
TI  - Molecular regulation of gene expression of catecholamine biosynthetic enzymes by
      stress: sympathetic ganglia versus adrenal medulla.
AB  - Stress induces tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene
      expression in sympathetic ganglia and adrenal medulla (AM). However, distinct
      molecular mechanisms appear to regulate these genes in these locations. The
      elevation of TH mRNA in response to single immobilization stress (IMO) in AM is
      robust, but transient, while the induction of TH and DBH mRNAs in sympathetic
      ganglia is slower and more long lasting. Injections of adrenocorticotropic
      hormone (ACTH) elicited induction of TH and DBH gene expression in rat
      sympathetic ganglia, but not in AM. The superior cervical (SCG) and stellate
      (StG) ganglia, but not AM, were found to express mRNA for the MC-2 receptor, the
      major ACTH responsive receptor in adrenal cortex. IMO led to increase in MC-2
      receptor mRNA levels in SCG. Thus, ACTH, via the MC-2 receptor, may be directly
      involved in the stress-elicited regulation of norepinephrine biosynthesis in
      sympathetic ganglia. The signaling pathways triggered by IMO differed in these
      locations. In AM, IMO triggered activation of the MAP kinase, JNK, and induction
      of AP1 factors, Egr1 and phosphorylation of CREB. In contrast in the SCG, with
      IMO we did not observe changes in JNK and little binding to the AP1 motif of the
      TH promoter. However, there was an increase in CREB binding to the CRE site of
      the TH promoter. The results reveal differential mechanisms of regulation of
      catecholamine biosynthetic enzymes by stress in two components of the
      sympathoadrenal system and should provide basis for possible selective
      pharmacologic interventions.

PMID- 15240394
TI  - Genetic mechanisms for adrenergic control during stress.
AB  - Cortisol and epinephrine released in response to stress are replenished via
      activation of the hypothalamic-pituitary-adrenal (HPA or stress) axis.
      Immobilization (IMMO) stress in rats stimulates epinephrine production in part
      via the gene encoding the epinephrine-synthesizing enzyme phenylethanolamine N
      methyltransferase (PNMT). PNMT mRNA rose up to 7.0-fold with acute or chronic
      stress. Two transcription factors mediating stress induction of the PNMT gene are
      the glucocorticoid receptor (GR) and Egr-1, which interact with -533, -759, and 
      773 bp, and -165 bp binding sites in the rat PNMT promoter, respectively. To
      identify molecular mechanisms involved, effects of hypoxic stress on PNMT
      promoter activity were examined in PC12 cells transfected with the PNMT promoter
      luciferase reporter gene construct pGL3RP893. Oxygen reduction to 5% increased
      PNMT promoter-driven luciferase expression, with maximum activity at 6 h.
      Pretreatment of the cells with protein kinase A (PKA) and protein kinase C (PKC)
      inhibitors, H-89 and GF109203X, respectively, attenuated the rise in luciferase.
      Similarly, PKA-deficient PC12 cells transfected with pGL3RP893 and exposed to
      hypoxia also showed attenuated PNMT promoter-driven luciferase expression.
      Mutation of the Egr-1 binding site completely prevented PNMT promoter activation,
      indicating that Egr-1 is essential to the stress response. Consistent with this
      result, hypoxia increased Egr-1 protein. Hypoxia also increased endogenous PNMT
      mRNA. However, a shift to intron-retaining mRNA from which truncated,
      nonfunctional protein is produced, occurred, suggesting that posttranscriptional
      regulation may be an important genetic mechanism controlling adrenergic
      expression and hence, epinephrine, during stress.

PMID- 15240395
TI  - Hypertonic saline and immobilization induce Fos expression in mouse brain
      catecholaminergic cell groups: colocalization with tyrosine hydroxylase and
      neuropeptide Y.
AB  - The aim of the present study was to reveal stress-type dependent differences in
      hindbrain catecholaminergic (CA) cells and parabrachial nuclei (PBN) in the wild
      type mouse. Neuronal activities were evaluated based on the incidence of Fos
      labeling analyzed 60 min after injection of hypertonic saline (HS; 400 microL,
      1.5 M, i.p.) or 120 min of immobilization (IMO) stress. The phenotypic nature of
      neurons was identified by costaining of Fos with either tyrosine hydroxylase (TH)
      or the neuropeptide Y (NPY) antibody. Generally, HS elicited broader Fos-staining
      than IMO. In comparison with IMO, HS induced more extensive Fos activation in the
      nucleus tractus solitarii-area postrema complex, and in TH- and NPY-positive
      cells in the A1 and C1 areas. Locus coeruleus (LC) cells displayed similar Fos
      activation after HS and IMO, and both stimuli also evoked evident TH-Fos
      colocalizations. Both stimuli also induced TH-Fos costainings in the A5 area. In
      contrast, IMO failed to activate PBN cells. The data indicate that the activity
      of TH and NPY hindbrain neurons responds differently to HS and IMO stress,
      supporting the notion that different stressors have different effects on the
      activity of autonomic centers.

PMID- 15240397
TI  - Generating mouse models for studying the function and fate of intrinsic cardiac
      adrenergic cells.
AB  - Embryos lacking the ability to synthesize epinephrine and norepinephrine die
      (probably due to cardiac failure) without exogenous supplementation while mutant
      neonates can grow into fertile adults without supplementation. These experiments
      define a critical period during embryogenesis, when norepinephrine and/or
      epinephrine are essential for mouse development. The critical period is prior to
      sympathetic innervation of the heart and prior to synthesis of catecholamines by
      the adrenal medullae. Recent work indicates that the developing heart is likely
      to be a major source of catecholamines in the developing mammalian embryo. The
      spatial pattern of biosynthetic enzymes suggests an association of the intrinsic
      cardiac adrenergic cells with the developing pacemaker and cardiac conduction
      cells. To address the functional characteristics and the fate of these cardiac
      adrenergic cells, we have developed two mouse models that allow us to identify
      and to characterize the adrenergic cells and their descendants.

PMID- 15240396
TI  - Localization and regulation of phenylethanolamine N-methyltransferase gene
      expression in the heart of rats and mice during stress.
AB  - Recently we have described the existence of phenylethanolamine N
      methyltransferase (PNMT) mRNA in the heart of adult rats. In this study, we
      report the first data on distribution of the PNMT protein in rat hearts, which
      follows the distribution of PNMT mRNA (high levels in the atria and low levels in
      ventricles). The main aim of this study was to determine the localization of the
      PNMT mRNA in the heart and to examine whether gene expression of this enzyme is
      affected by immobilization (IMO) stress in a time-dependent manner. PNMT mRNA
      levels were detected in all seven studied parts of the heart (atria without and
      with intramural ganglion cells, ventricles, and septum), with the highest levels
      in the left atrium and its ganglionic part. Both Southern blot and sequencing
      verified the specificity of PNMT detected by RT-PCR. Single IMO for 2-h increased
      gene expression of PNMT, as determined by both RT-PCR and Real-Time PCR in the
      right and left atria. Surprisingly, the ganglionic parts of the atria did not
      respond to stress stimulation. Peak levels of PNMT mRNA were found in the 3-h
      interval after the IMO terminated, and also 24 h after the first or sixth IMO.
      Expression of aromatic L-amino acids decarboxylase and dopamine-beta-hydroxylase
      has also been detected in the heart of control and stressed rats. In the atria,
      the effect of stress is clearly modulated by glucocorticoids, since in mice with
      corticotrophin-releasing hormone knocked out gene the immobilization-induced
      increase in the PNMT mRNA levels seen in wild-type animals was abolished. Thus,
      our data have shown that gene expression of the PNMT is localized, not
      predominantly in cardiac ganglion cells, but in a wide range in atrial
      cardiomyocytes. Mechanism responsible for the regulation of stress-induced
      increase of PNMT gene expression in cardiac atria is clearly dependent on the
      presence of glucocorticoids.

PMID- 15240399
TI  - Changes in gene expression of phenylethanolamine N-methyltransferase in the
      transplanted human heart.
AB  - Heart transplantation (HTx) is an accepted treatment for precisely defined
      patients with chronic congestive heart failure; however, as a result of the
      procedure, the graft is completely denervated. Our study focused on the
      catecholamine biosynthetic pathway, that is, the production of epinephrine, which
      is known to have positive chronotropic and inotropic effects on the heart. mRNA
      levels of the phenylethanolamine N-methyltransferase (PNMT), the enzyme
      catalyzing epinephrine synthesis in myocardial tissue, were determined in 18
      patients (0 to 10 yr after HTx). Samples of myocardium were obtained from the
      right ventricle at the time of a routine endomyocardial biopsy performed for the
      diagnosis of graft rejection. Results were correlated with the following clinical
      parameters: heart rate, heart rate variability, blood pressure, graft systolic
      function, and the presence of the rejection. We observed that heart PNMT mRNA
      levels were significantly higher during the first 3 yr as compared to longer
      periods after HTx. Also, a decrease in the average heart rate and an increase in
      the heart rate variability were documented. Levels of the PNMT mRNA do not
      correlate with blood pressure, left ventricular systolic function at rest, and
      rejection. Thus, a gradual decrease of the heart rate and an increase in the
      heart rate variability after HTx is considered to be a sign of cardiac graft
      reinervation. We speculate that the increased PNMT transcription in human
      myocardium in early intervals after HTx reflects "autonomous sympathicotrophy." A
      decrease in the PNMT gene expression with the number of years after HTx could be
      a consequence of the reinnervation process.

PMID- 15240398
TI  - Modulation of catecholamine-synthesizing enzymes in the rat heart by repeated
      immobilization stress.
AB  - Stress is one of the major risk factors responsible for the increased incidence
      of a number of common life-threatening disorders, predominantly of cardiovascular
      origin. The aim of the present study was to establish the effect of repeated
      immobilization stress on gene expression and protein levels of aromatic L-amino
      acid decarboxylase (AADC) and phenylethanolamine N-methyltransferase (PNMT) in
      cardiac left and right atria. In the process of repeated immobilization, rats
      were immobilized 2 h daily for 7 days and killed 3 h after the last
      immobilization. Gene expression was determined by regular and real-time reverse
      transcription with subsequent polymerase chain reaction, and protein levels were
      determined by Western blot analysis. In cardiac atria, we identified mRNA for
      AADC and PNMT. Repeated immobilization stress did not affect AADC mRNA levels.
      However, repeated immobilization significantly increased PNMT mRNA levels
      compared with unstressed control animals. No further increase was observed
      compared with adapted control rats (rats immobilized six times for 2 h daily and
      decapitated 24 h after the sixth immobilization). AADC protein levels
      corresponded with mRNA levels of this enzyme. However, we were not able to detect
      PNMT immunoreactive protein. The observed elevation in the gene expression of
      PNMT mRNA levels in the heart may be involved in the increased risk of
      cardiovascular diseases with stress.

PMID- 15240400
TI  - Emotional stress-induced Tako-tsubo cardiomyopathy: animal model and molecular
      mechanism.
AB  - Emotional or physical stress triggers Tako-tsubo cardiomyopathy in postmenopausal
      females, which is characterized by an elevation of the ST segment in the
      electrocardiogram (ECG) and left ventricular apical ballooning in the left
      ventriculogram (LVG). Immobilization stress (IMO) of rats can reproduce these ECG
      and LVG changes, both of which are normalized by combined blockade of alpha- and
      beta-adrenoceptors. An increase of serum estrogen partially attenuated these
      cardiac changes. IMO induced a rapid activation of p44/p42 mitogen-activated
      protein kinase, followed by a transient upregulation of immediate early genes
      (IEG) in the coronary artery and myocardium. Blocking of both alpha- and beta
      adrenoceptors eliminated the upregulation of IEG induced by stress, while alpha-
      or beta-agonists upregulated IEG in the perfused heart. Heat shock protein 70 was
      induced in the aorta, coronary artery, and the myocardium. Natriuretic peptide
      genes (ANP and BNP) were also upregulated in the myocardium. Sequential gene
      expression can be considered as an adaptive response to stress. Activation of
      alpha- or beta-adrenoceptors is the primary trigger of emotional stress-induced
      cardiac changes.

PMID- 15240401
TI  - Mouse mutants for the study of corticotropin-releasing hormone receptor function:
      development of novel treatment strategies for mood disorders.
AB  - In today's psychiatry there is a great deal of interest in the development of
      compounds with a novel mechanism of action that diverge from the classical
      catecholaminergic neurotransmitter system targets. Within the last few years, it
      has become increasingly evident that the neuroendocrine and behavioral phenotypes
      of mood and anxiety disorders are at least in part mediated by modulation of
      corticotropin-releasing hormone (CRH) neurocircuitries and that normalization of
      an altered neurotransmission after treatment may lead to restoration of disease
      related changes. Although this concept was originally derived from peripheral
      hypothalamic-pituitary-adrenocortical (HPA) assessments in depressed patients,
      central CRH neuropeptidergic circuits other than those driving the peripherally
      accessible HPA system may be overactive and could be therapeutic targets of
      antagonist actions. Genetically engineered mice provide a novel and useful tool
      to study the endogenous mechanisms underlying aberrant behavior and CRH
      neurocircuitry regulation. The results obtained from conventional and conditional
      mutant mice indicate that CRH type 1 receptors may be the primary target to which
      to direct selective nonpeptide compounds. Moreover, beyond the encouraging
      preclinical studies, the first clinical open trial supports the notion that CRH
      type 1 receptors can be safely and effectively antagonized.

PMID- 15240402
TI  - Catecholamine synthesizing enzymes and their modulation by immobilization stress
      in knockout mice.
AB  - The c-fos knockout mice (c-fos KO) and corticotropin-releasing hormone knockout
      mice (CRH KO) can serve as interesting models for studying mechanisms involved in
      response of the organism to stress, focused mainly on the hypothalamic-pituitary
      adrenal (HPA) axis and sympathoadrenal system (SAS). The present study focused on
      the investigation of changes in gene expression of catecholamine biosynthesizing
      enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and
      phenylethanolamine N-methyltransferase (PNMT) in adrenal medulla of c-fos KO and
      CRH KO mice stressed by immobilization. Levels of TH, DBH, and PNMT mRNA were
      determined by reverse transcription-polymerase chain reaction (RT-PCR). Single
      immobilization for 2 h significantly increased adrenomedullary TH, DBH, and PNMT
      mRNA levels in both c-fos KO and wild-type (WT) mice compared to unstressed
      controls. In CRH KO mice, PNMT gene expression was not increased to the same
      extent after single, but especially after repeated immobilization as in WT mice,
      in contrast to TH and DBH mRNA levels. Thus, our data indicate that CRH
      deficiency can influence the PNMT mRNA level in adrenal medulla during stress,
      confirming the idea that the HPA axis plays the crucial role in PNMT gene
      regulation in mice. On the other hand, c-Fos protein probably does not play a
      crucial role in TH, DBH, and PNMT gene expression in adrenal medulla under stress
      conditions.

PMID- 15240403
TI  - GABAergic mechanisms constraining the activity of the hypothalamo-pituitary
      adrenocortical axis.
AB  - There are two major inhibitory mechanisms that constrain the activity of the
      hypothalamo-pituitary-adrenocortical axis: the hormonal negative feedback and the
      neural inhibition including that posed by the GABAergic neurons. This chapter
      summarizes our recent morphologic and functional findings on the role of gamma
      aminobutyric acid (GABA) in the transcriptional regulation of hypophyseotropic
      neuropeptide genes in the parvocellular neurosecretory cells of the hypothalamic
      paraventricular nucleus (PVH). We used organotypic hypothalamic slice cultures
      and in vivo microinjection protocols in combination with in situ histologic and
      ultrastructural procedures to address the role of local interneurons in the
      regulation of hypothalamic effector neurons. Under basal conditions, an intrinsic
      GABAergic mechanism in the PVH microenvironment was revealed that by itself,
      without limbic contribution, impinged a tonic inhibitory influence on the
      parvocellular corticotropin-releasing hormone (CRH) neurons in vitro. In vivo,
      remote inputs were superimposed on the local circuit, allowing differential
      transcriptional regulation of CRH and arginine vasopressin (AVP) genes in the
      hypophyseotropic neurons. During stress, GABAergic cells that are known to
      project to the PVH become activated and are involved in restraining the cellular,
      transcriptional, and hormonal responses to stress.

PMID- 15240404
TI  - Maternal genotype can influence the outcome of a study on mutant animals.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis plays a crucial role in stress. One
      of its central regulatory components is arginine-vasopressin (AVP). We studied
      the role of AVP in acute restraint in AVP-deficient mutant Brattleboro rats (AVP
      ), but our results were variable. The early life period is important in the later
      stress reactivity of the animals. We realized that our AVP- pups could be born
      from AVP+ (heterozygous) or from AVP- mothers. Therefore, we asked whether the
      genotype of the mother could explain the variability. Adult rats from AVP+ and
      AVP- mothers were stressed with 60 min of restraint. Trunk blood was collected
      for measuring hormone content by radioimmunoassay. All offspring of AVP+ mothers
      had similar adrenocorticotropic hormone (ACTH) responses to restraint, whereas
      the AVP- rats born to AVP- mothers showed reduced ACTH reactivity. Our results
      show that the AVP- genotype of the mother can decrease the stress reactivity of
      AVP- Brattleboro rats. In mutant/knockout animals, family background should be
      taken into account as well as the genotype of the studied animals.

PMID- 15240405
TI  - Angiotensin II AT1 receptor antagonism downregulates stress-related gene
      expression in brain microvessels from spontaneously hypertensive and normotensive
      rats.
AB  - We studied the effect of treatment with the Angiotensin II AT(1) receptor
      antagonist candesartan (0.3 mg/kg/day via osmotic minipumps for 4 weeks compared
      with administration of vehicle) in brain microvessels in adult spontaneously
      hypertensive rats (SHR) that were vulnerable to stroke and normotensive control
      rats (WKY). At the dose administered, candesartan normalized blood pressure in
      SHR without significantly affecting blood pressure in WKY rats. We performed the
      gene expression analysis in rat brain microvessels using the Affymetrix Gene Chip
      Expression Analysis Technique. From a total of 8,799 probe array sets analyzed,
      we found abundant abnormalities in gene expression in SHR. Because stress has
      been suggested as a precipitant factor in brain ischemia and treatment with AT(1)
      receptor antagonist candesartan prevents the hormonal and sympathoadrenal
      reaction to isolation stress and protects from stress-induced gastric ulcers, we
      focused on the expression of stress-related genes. We found a higher number of
      probe array sets modified by candesartan treatment in normotensive WKY rats than
      in hypertensive SHR. AT(1) receptor blockade decreased the transcription levels
      of the stress-related tyrosine kinase receptor, stathmin, and fibroblast growth
      receptor genes in WKY and SHR rats. Our results indicate that Angiotensin II and
      its AT(1) receptors can influence gene expression independently of the effects on
      blood pressure. In addition, AT(1) receptor regulation of stress-related genes in
      brain microvessels may explain the proposed association between stress and
      ischemic disorders of the brain.

PMID- 15240406
TI  - New tools to monitor stress using non-invasive PET imaging.
AB  - Noninvasive imaging using positron emission tomography (PET) is playing an
      increasing role in monitoring biochemical changes in vivo in various diseases.
      For example, many of the neurochemical systems activated by stress can be
      monitored using this technique. Examples of neurotransmitter interactions with
      CRH, serotonin, dopamine, and muscarinic cholinergic receptors demonstrate this
      approach.

PMID- 15240407
TI  - Anatomical and functional imaging of metastatic pheochromocytoma.
AB  - Although in the majority of patients with pheochromocytoma the tumor is localized
      in the adrenal, up to 26% of patients have malignant/metastatic disease.
      Metastatic disease should be ruled out before initial surgery is attempted.
      Anatomical imaging modalities (computed tomography or magnetic resonance imaging)
      should be done first over the adrenals, and if negative over the abdomen and if
      no tumor is found, then the chest and neck should be covered. Regardless of the
      anatomical imaging results functional imaging with [123-I]- or [131-I]
      metaiodobenzylguanidine (MIBG) scintigraphy should be done to corroborate the
      diagnosis. Negative MIBG scans should be followed by positron emission tomography
      (PET) studies with specific ligands like [18-F]-dopamine. Persistently negative
      evaluations should be followed by PET studies with non-specific ligands such as
      [18-F]-deoxyglucose or somatostatin receptor scintigraphy.

PMID- 15240408
TI  - Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder.
AB  - Panic disorder serves as a clinical model for testing whether mental stress can
      cause heart disease. Our own cardiologic management of panic disorder provides
      case material of recurrent emergency room attendances with angina and
      electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation,
      ventricular fibrillation), and documented coronary artery spasm, in some cases
      with coronary spasm being complicated by coronary thrombosis. Application of
      radiotracer catecholamine kinetics and clinical microneurography methodology
      suggests there is a genetic predisposition to panic disorder that involves faulty
      neuronal norepinephrine uptake, possibly sensitizing the heart to symptom
      generation. During panic attacks there are large sympathetic bursts, recorded by
      clinical microneurography in the muscle sympathetic nerve neurogram, and large
      increases in cardiac norepinephrine spillover, accompanied by surges of adrenal
      medullary epinephrine secretion. In other conditions such as heart failure and
      presumably here also, a high level of sympathetic nervous activation can mediate
      increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y
      (NPY), is released from the cardiac sympathetics during panic attacks, an
      intriguing finding given that NPY can cause coronary artery spasm. There is
      ongoing, continuous release of epinephrine from the heart in panic sufferers,
      perhaps attributable to epinephrine loading of cardiac sympathetic nerves by
      uptake from plasma during panic attacks, or possibly to in situ synthesis of
      epinephrine through the action of intracardiac phenylethanolamine-N
      methytransferase (PNMT) activated by repeated cortisol responses. We have used
      internal jugular venous sampling and measurement of overflowing lipophilic brain
      monoamine metabolites to quantify brain norepinephrine and serotonin turnover in
      untreated patients with panic disorder. We find normal norepinephrine turnover
      but a marked increase in brain serotonin turnover in patients with panic
      disorder, in the absence of a panic attack, which presumably represents an
      underlying neurotransmitter substrate for the condition.

PMID- 15240409
TI  - Cardiovascular responses to stress after carotid baroreceptor denervation in
      humans.
AB  - Iatrogenic bilateral denervation of carotid sinus baroreceptors may occur as a
      complication of carotid body tumor resection and radiation therapy of the neck.
      The acute phase of the resulting syndrome of baroreflex failure is characterized
      by a limited blood pressure buffering capacity against excessive rise or fall in
      response to emotional and physical stimuli like sexual arousal and cold.
      Paroxysms of severe hypertension and tachycardia, accompanied by excessive
      increments in sympathetic tone and catecholamine plasma levels, were ascribed to
      loss of tonic inhibitory influence of baroreceptors on sympathetic tone.
      Bilateral anesthetic blockade of baroreceptor afferent nerves was shown to result
      in a strong increase in muscle sympathetic nerve activity and disruption of its
      normal patterning. This chapter reviews our findings on the long-term effects of
      iatrogenic baroreflex trauma on the hemodynamic responses to pharmacological,
      physical, and emotional stress in the autonomic function laboratory as well as
      under daily life conditions. Chronic attenuation of baroreflex sensitivity after
      carotid body tumor resection and neck irradiation results in an increased blood
      pressure variability. However, unopposed sympathetic activation in response to
      physical and emotional stress appears to be limited to the acute phase of
      baroreflex failure.

PMID- 15240410
TI  - Congenital dopamine-beta-hydroxylase deficiency in humans.
AB  - Dopamine-beta-hydroxylase (DbetaH) deficiency is a rare autosomal dominant
      disorder. Due to the absence of DbetaH, there is a blocked conversion of dopamine
      into norepinephrine. The biochemical hallmark of this syndrome consists of a
      complete absence of plasma norepinephrine and epinephrine levels in conjunction
      with an increased plasma dopamine level. Several mutations in the gene that
      encodes for DbetaH have been described. Up to now, worldwide, 12 patients have
      been reported. The most important clinical feature is a severe orthostatic
      hypotension. In addition, several other clinical features like blepharoptosis,
      hyperflexible joints, high palate, sluggish deep tendon reflexes, and a mild
      normocytic anemia have been described. The only effective treatment of DbetaH
      deficiency is L-threo-3,4-dihydroxyphenylserine (DOPS). DOPS is converted
      directly into norepinephrine. Treatment with DOPS results in a sustained relief
      of orthostatic symptoms.

PMID- 15240411
TI  - Behavioral and neuroendocrine changes during mental stress and repeated treatment
      with antidepressants in healthy men.
AB  - Excessive stress loadings in daily life are believed to play a role in the
      development of affective disorders. Our recent finding of enhanced neuroendocrine
      activation during stress of hypoglycemia after repeated antidepressant treatment
      in healthy men supports the hypothesis that the clinical effects of
      antidepressant treatment may be partly due to the adjustment of the stress
      response, which was reported to be blunted in depressive patients. The present
      double-blind placebo-controlled study investigated the effects of 6 days of
      treatment with the antidepressants citalopram or tianeptine on neuroendocrine
      activation during mental stress. Blood pressure, heart rate, and salivary
      cortisol values were measured. The stress procedure, lasting 17 min, consisted of
      a short intelligence test followed by the Stroop word-color interference test.
      Citalopram treatment was associated with a significant enhancement of stress
      related increase in systolic and diastolic blood pressure. No differences were
      observed in the heart rates and salivary cortisol. Comparisons based on cluster
      analysis revealed that subjects with poor performance in the Stroop test
      displayed a significantly lower rise of systolic and diastolic blood pressure
      values after the stress procedure and lower prestress cortisol levels in saliva
      when compared to the good performing subjects. Our findings show that
      antidepressant treatment can enhance the neuroendocrine response also during
      mental stress, and suggest that mental performance during stress is related to
      the pattern of cardiovascular and adrenocortical activation.

PMID- 15240412
TI  - Oxidative stress to dopaminergic neurons as models of Parkinson's disease.
AB  - The effects of exogenous toxins (MPP(+), rotenone) and potentially neurotoxic
      properties of levodopa (L-DOPA) on the survival rate of dopaminergic neurons in
      dissociated primary culture are presented. Dopamine agonists show a capacity to
      counteract MPP(+)-toxicity. Moreover, a preserving potential of the antioxidant
      and bioenergetic coenzyme Q(10) (CoQ(10)) on the activities of tyrosine
      hydroxylase (TH), complexes I and II of the respiratory chain, and hexokinase
      activity in striatal slice cultures against MPP(+) is demonstrated.

PMID- 15240413
TI  - Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal
      adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis
      study.
AB  - Thyroid function plays an important role in the regulation of overall metabolic
      rate and lipid metabolism. However, it is uncertain whether thyroid hormones
      directly affect lipolysis in adipose tissue and to what extent those changes
      contribute to overall metabolic phenotype. Our study was designed, using the
      microdialysis technique, to determine basal and isoprenaline-stimulated local
      lipolysis and to determine local concentrations of lipolysis-regulating
      catecholamines in abdominal subcutaneous adipose tissue in 12 patients with
      hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects.
      Plasma norepinephrine (NE) concentrations in hypothyroid subjects were
      significantly higher than in the control and hyperthyroid groups. In contrast,
      systemic, adipose NE levels in hypothyroid patients were decreased relative to
      controls. Hyperthyroidism, on the other hand, resulted in four-fold higher
      adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose
      tissue was significantly attenuated in hypothyroid patients and markedly
      increased in hyperthyroid patients in comparison with the control group. In
      addition to differences in basal lipolysis, hypothyroidism resulted in
      attenuated, and hyperthyroidism in enhanced, lipolytic response to local
      stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results
      demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly
      modulated by thyroid function. We suggest that thyroid hormones regulate
      lipolysis primarily by affecting local NE concentration and/or adrenergic
      postreceptor signaling.

PMID- 15240414
TI  - Effects of real and simulated microgravity on response of sympathoadrenal system
      to various stress stimuli.
AB  - Changes in plasma levels of epinephrine (EPI) and norepinephrine (NE) were
      investigated in humans exposed to physical exercise (WL), to psychic stressor
      (mental arithmetic test, MAT), and to oral glucose administration (oGTT) before
      and during a stay in microgravity (real space flight, SF) or in simulated
      microgravity (head-down bed rest, HDBR). A permanent cannula inserted into the
      cubital vein and a special appliance, Plasma-03, were used for blood collection,
      plasma separation, and freezing of samples during SF. Plasma EPI, NE,
      dihydroxyphenylglycol (DHPG), and dihydroxyphenylalanine (DOPA) levels were
      measured by the high-pressure liquid chromatography (HPLC) method. Basal plasma
      EPI, NE, DHPG, and DOPA levels were found within the range of control values
      during SF. Preflight WL produced high increase in plasma NE and moderate
      elevation of plasma EPI, DHPG, and DOPA levels. Exaggerated exercise induced
      increases in plasma NE, DHPG, EPI, and DOPA levels were demonstrated in real
      microgravity. A return to preflight responses of sympathoadrenal system was seen
      after the landing. Plasma EPI, NE, and DHPG responses to MAT were relatively
      small, but increased during SF. During the oGTT the plasma EPI levels were
      slightly reduced in microgravity. Similarly as in SF, WL in HDBR was followed by
      significantly exaggerated responses of plasma catecholamines. These results show
      that both somatic and psychological stressors are able to induce an increased
      activation of sympathoadrenal system during SF or simulated microgravity in HDBR.

PMID- 15240415
TI  - Effects of space flight and -6 degrees bed rest on the neuroendocrine response to
      metabolic stress in physically fit subjects.
AB  - The aim of this study was to evaluate the association of plasma epinephrine (EPI)
      and norepinephrine (NE) responses to insulin-induced hypoglycemia (ITT) 3 weeks
      before the space flight (SF), on the fifth day of SF, on days 2 and 16 after
      landing in the first Slovak astronaut, and before and on the fifth day of
      prolonged bed rest (BR) in 15 military aircraft pilots, aged 33.5 +/- 1.4 years,
      body mass index (BMI) 26.5 +/- 0.7 kg/m(2), maximal oxygen uptake (VO(2max)) 55.2
      +/- 2.4 mL/kg/min, who volunteered for the study. ITT was induced by i.v.
      administrations of 0.1 IU/kg body weight insulin (Actrapid HM) in a bolus.
      Insulin administration led to a comparable hypoglycemia in preflight, actual
      flight conditions, and before and after bed rest. ITT led to a pronounced
      increase in EPI levels and moderate increase in NE in preflight studies. However,
      an evidently reduced plasma elevation of EPI was found after insulin
      administration during SF and during BR. Thus, during the real microgravity in SF
      and simulated microgravity in BR, ITT activates the adrenomedullary system to
      less extent that at conditions of the Earth's gravitation. Post-flight changes in
      EPI and NE did not differ from those of preflight values, since SF was relatively
      short (8 days) and the readaptation to Earth's gravitation was fast. It seems
      that an increased blood flow in brain might be responsible for the reduced EPI
      response to insulin. Responses to ITT in physically fit subjects indicate the
      stimulus specificity of the deconditioning effect of 5 days of bed rest on the
      stress response.

PMID- 15240416
TI  - Effects of endurance training on endocrine response to physical exercise after 5
      days of bed rest in healthy male subjects.
AB  - The study was designed to evaluate how a bout of endurance training (ET)
      influences the endocrine response after head-down bed rest (HDBR). Eleven healthy
      males completed the study, which consisted of a 6-wk ET followed by 5 days of -6
      degrees head-down HDBR. Treadmill exercise at 80% of pretraining maximal aerobic
      capacity (VO(2max)) was performed before and after ET as well as after HDBR. ET
      increased VO(2max) by 13%. The response of norepinephrine was attenuated after ET
      and exaggerated after HDBR (P < 0.001). The differences in epinephrine responses
      were not statistically significant. The responses of cortisol and plasma renin
      activity (PRA) were unchanged after ET and were enhanced after HDBR (P < 0.001).
      The response of growth hormone after HDBR was reduced (P < 0.05). Only the change
      in cortisol response was associated with the increment of VO(2max) after ET (r =
      0.68, P < 0.01). Endurance training failed to completely prevent changes in
      endocrine responses seen after HDBR. Improvement of physical fitness was
      associated with an enhancement of the cortisol response to exercise following the
      period of bed rest.

PMID- 15240417
TI  - Does orthostatic stress influence the neuroendocrine response to subsequent
      hypoglycemia in humans?
AB  - Neuroendocrine response to stress stimuli is influenced by previous stimuli of
      different nature. The aim of the study was to test whether antecedent orthostatic
      stress may affect the neuroendocrine response to subsequent hypoglycemia. A group
      of 12 (6 men, 6 women) nonobese, healthy volunteers aged 19 to 27 y (mean 24 +/-
      0.8) participated in the study in two sessions: controlled insulin-induced
      hypoglycemia to 2.7 mmol/L for 15 min either with or without antecedent
      orthostatic stress (30 min of 60 degrees head-up tilt before insulin
      administration). Orthostatic stress caused a significant decrease in plasma
      volume (-9.6%; P < 0.001) and a significant increase in plasma renin activity,
      aldosterone, norepinephrine (P < 0.01), and adrenocorticotropic hormone (ACTH)
      concentrations (P < 0.05) in all subjects. Growth hormone response to
      hypoglycemia was diminished in women (P < 0.01). The epinephrine response to
      hypoglycemia was diminished in women in comparison to men (P < 0.001), but was
      unaffected by antecedent orthostatic stress. Hypoglycemia failed to induce the
      ACTH release after its elevation during orthostatic stress. ACTH response to
      moderate hypoglycemia without previous orthostatic stress was evident only in men
      in comparison to women (P < 0.05). We conclude that the epinephrine, growth
      hormone, and ACTH responses to hypoglycemia were diminished in women. Except
      ACTH, the neuroendocrine response to mild hypoglycemia was not affected by
      previous orthostatic stress in healthy subjects. In the case of ACTH, the first
      stress stimulus is consequential for the subsequent response of this hormone,
      probably due to short-loop negative feedback effects.

PMID- 15240418
TI  - Development of enantioselective immunoassays for free plasma metanephrines.
AB  - The development of an enantioselective radioimmunoassay (RIA) and enzyme
      immunoassay (EIA) for L-normetanephrine (NM) and L-metanephrine (M) were studied.
      Prior to the immunoassay, the protein matrix of the ethylenediaminetetraacetic
      acid (EDTA) plasma samples was removed by acid precipitation, followed by
      derivatization of the L-metanephrines to N-acyl-L-metanephrines. For the EIA, N
      acyl-L-NM and N-acyl-L-M were bound to the surface of microtiter plates. Acylated
      L-metanephrines from the sample and solid-phase-bound N-acyl-L-NM or N-acyl-L-M
      competed for a fixed number of rabbit anti-N-acyl-NM or anti-N-acyl-M antibody
      binding sites. When the system was in equilibrium, free antigens and free antigen
      antibody complexes were removed by washing. The antibodies bound to the
      respective solid-phase N-acyl-L-NM or N-acyl-L-M were detected by a goat anti
      rabbit IgG-peroxidase conjugate using tetramethyl benzidine (TMB) as a substrate.
      The RIAs were conventional double antibody tests using the above rabbit antisera
      and specific (125)I-N-acyl-L-metanephrine tracers. Chiral recognition of the L
      enantiomers was observed not only for the native molecules but for all N-acyl
      derivatives tested. The cross-reactivity to the corresponding D-enantiomers was
      always <1%. The detection limits were found to be approximately 0.04 nmol/L (7.5
      pg/mL) for M and 0.08 nmol/L (15 pg/mL) for NM in RIA and EIA.

PMID- 15240419
TI  - Indirect Sertoli cell-mediated ablation of germ cells in mice expressing the
      inhibin-alpha promoter/herpes simplex virus thymidine kinase transgene.
AB  - In the present study, we describe a novel mouse model for inducible germ cell
      ablation. The mice express herpes simplex virus thymidine kinase (HSV-TK) under
      the inhibin-alpha subunit promoter (Inhalpha). When adult transgenic (TG) mice
      were treated with famciclovir (FCV) for 4 wk, their spermatogenesis was totally
      abolished, with only Sertoli cells and few spermatids remaining in the
      seminiferous tubules. However, testicular steroidogenesis was not affected.
      Shorter treatment periods allowed us to follow up the progression of germ cell
      death: After 3 days, spermatogonia and preleptotene spermatocytes were no longer
      present. After a 1-wk treatment, spermatogonia, preleptotene, and zygotene
      spermatocytes were missing and the amount of pachytene spermatocytes was
      decreased. After a 2-wk treatment, round and elongating spermatids were present.
      During the third week, round spermatids were lost and, finally, after a 4-wk
      treatment, only Sertoli cells and few spermatids were present. Interestingly, the
      transgene is detected in Leydig and Sertoli cells but not in spermatogonia. This
      suggests that FCV is phosphorylated in Sertoli cells, and thereafter, leaks to
      neighboring spermatogonia, apparently through cell-cell junctions present,
      enabling trafficking of phosphorylated FCV. Because of the many mitotic divisions
      they pass through, the spermatogonia are very sensitive to toxins interfering
      with DNA replication, while nondividing Sertoli cells are protected. Using
      transillumination-assisted microdissection of the seminiferous tubules, the gene
      expression patterns analyzed corresponded closely to the histologically observed
      progression of cell death. Thus, the model offers a new tool for studies on germ
      cell-Sertoli cell interactions by accurate alteration of the germ cell
      composition in seminiferous tubules.

PMID- 15240420
TI  - A reproducible two-step culture system for isolated primary mouse ovarian
      follicles as single functional units.
AB  - A reproducible two-step culture system for isolated mouse ovarian follicles
      smaller than 100 microm (type 3a follicles) was designed. First, isolated
      follicles were grown in single droplets of alpha-minimal essential medium (MEM)
      without (deoxy)ribonucleosides at a lower concentration of fetal bovine serum
      (FBS; 1%) for 6 days with mechanical prohibition of thecal cell attachment.
      Growing follicles reaching at least 100 microm were transferred to alpha-MEM
      medium enriched with a higher concentration (5%) of FBS to allow attachment and
      were cultured subsequently for an additional 12 days. Overall, more than 85% of
      the follicles survived the first culture step, and oocyte growth and granulosa
      cell proliferation had increased by 25% (P < 0.05). Follicle survival at Day 18
      was related to initial follicle diameters at isolation. Average meiotic
      maturation rates and estrogen secretion were lower compared to those of cultures
      starting with early preantral follicles of 100-130 microm. Although reverse
      transcription-polymerase chain reaction analysis revealed the presence of LH
      receptor mRNA in thecal cells, an exogenous androstenedione replacement resulted
      in an increase of estrogen production, suggesting substrate insufficiency. The
      time needed to grow from early preantral stages to in vitro ovulation is strongly
      dependent on the initial follicle diameter at isolation. Morphological
      characteristics of cultured follicles were suggestive for combined transforming
      growth factor beta deficiencies during in vitro culture.

PMID- 15240421
TI  - Androgen-dependent expression, gene structure, and molecular evolution of guinea
      pig caltrin II, a WAP-motif protein.
AB  - We determined the cDNA and gene structures of guinea pig caltrin II, a unique
      member of the calcium transporter inhibitors containing a whey acidic protein
      (WAP) motif, and we established that it is a secretory protein with a potential
      21-amino acid signal peptide in its N-terminus. Northern blot analysis and in
      situ hybridization histochemistry indicated that the expression of caltrin II is
      restricted to luminal epithelial cells in the seminal vesicles. Its message
      levels markedly decreased either after castration (and were restored by
      simultaneous administration of testosterone) or after treatment of the animals
      with estradiol, suggesting that the expression of caltrin II is androgen
      dependent. Recombinant caltrin II had an elastase-inhibitor activity. Comparison
      of sequence between the caltrin II and related genes and their molecular
      evolutionary analyses revealed that caltrin II and seminal vesicle secretory
      proteins (SVPs) appear to be evolved from a common ancestor gene that is made by
      the fusion of semenogelin and trappin genes. Caltrin II and SVPs lost the
      transglutaminase substrate domain and the WAP motif, respectively, within a
      single exon, resulting in the exertion of different functions.

PMID- 15240422
TI  - Effect of candidate vaginally-applied microbicide compounds on recognition of
      antigen by CD4+ and CD8+ T lymphocytes.
AB  - Vaginally applied antimicrobial compounds (microbicides) are being developed as
      an alternative method for preventing the spread of sexually transmitted diseases.
      In addition to identifying compounds effective against a spectrum of sexually
      transmitted pathogens, it will be important to ensure that these compounds are
      safe. Avoiding toxicity, inflammatory responses, or alteration of the function of
      resident immune cells are important considerations for the development of
      vaginally applied microbicides. Studies were performed with two classes of
      candidate microbicide compounds to determine if they would interfere with the
      recognition of antigen by CD4(+) and CD8(+) T lymphocytes. The presence of
      nontoxic concentrations of the anionic detergent cholic acid or the sulfated
      polymer lambda carrageenan did not inhibit recognition of immune peptide by
      antigen-specific T cells. However, antigen recognition by both CD4(+) and CD8(+)
      T lymphocytes was inhibited in the presence of the naphthalene sulfonate polymer
      PRO 2000. Brief (4-h) exposure of antigen-presenting cells or T cells to PRO 2000
      did not result in inhibition of antigen uptake and processing by antigen
      presenting cells or the ability of specific T cells to respond to antigen
      stimulation, suggesting that the inhibition was temporary. Binding of antibodies
      specific for CD18, CD8, and CD3 was impaired in the presence of PRO 2000,
      suggesting that the mechanism by which this microbicide inhibits T cell
      recognition of antigenic peptide may involve masking or internalization of
      surface proteins involved in T cell signaling or stabilizing T cell-antigen
      presenting cell interactions. The assays described in this study represent a
      useful means to screen candidate topical microbicide compounds for inappropriate
      interactions with immune cells and may be useful for prioritization of candidate
      microbicide compounds.

PMID- 15240423
TI  - Aberrant gene expression in organs of bovine clones that die within two days
      after birth.
AB  - Cloning by somatic nuclear transfer is an inefficient process in which some of
      the cloned animals die shortly after birth and display organ abnormalities. In an
      effort to determine the possible genetic causes of neonatal death and organ
      abnormalities, we used real-time quantitative reverse transcription-polymerase
      chain reaction to examine expression patterns of eight developmentally important
      genes (PCAF, Xist, FGFR2, PDGFRa, FGF10, BMP4, Hsp70.1, and VEGF) in six organs
      (heart, liver, spleen, lung, kidney, and brain) of both cloned bovines that died
      soon after birth (n=9) and normal control calves produced by artificial
      insemination. In somatic cloning of cattle, fibroblasts have often been used for
      doner nuclei, and the effect of the age of the fibroblast donor cells on gene
      expression profiles was investigated. Aberrant expressions of seven genes were
      found in these clones. The majority of aberrantly expressed genes were common in
      clones derived from adult fibroblast (AF) and in clones derived from fetal
      fibroblast (FF) compared to controls, whereas some genes were dysregulated either
      in AF cell-derived or in FF cell-derived clones. For the studied genes, kidney
      was the organ least affected by gene dysregulation, and heart was the organ most
      affected, in which five genes were aberrant. Most dysregulations (12 of 19) were
      up-regulation, but PDGFRa only showed down-regulation. VEGF, BMP-4, PCAF, and
      Hsp70.1 were extremely dysregulated, whereas the other four genes had a low level
      of gene dysregulation. Our results suggest that the aberrant gene expression
      occurred in most tissues of cloned bovines that died soon after birth. For each
      specific gene, aberrant expression resulting from nuclear transfer was tissue
      specific. Because these genes play important roles in embryo development and
      organogenesis, the aberrant transcription patterns detected in these clones may
      contribute to the defects of organs reported in neonatal death of clones.

PMID- 15240424
TI  - BARD1 expression during spermatogenesis is associated with apoptosis and
      hormonally regulated.
AB  - The BRCA1-binding RING-finger domain protein BARD1 may act conjointly with BRCA1
      in DNA repair and in ubiquitination, but it may also induce apoptosis in a BRCA1
      independent manner. In this study, we have investigated BARD1 expression during
      spermatogenesis. In contrast with BRCA1, which is expressed only in meiotic
      spermatocytes and early round spermatids, BARD1 is expressed during all stages of
      spermatogenesis. However, while spermatogonia expressed full-length BARD1 mRNA,
      later stages of spermatocyte precursors express predominantly a novel, shorter
      splice form BARD1beta. BARD1beta lacks the BRCA1-interacting RING finger but
      maintains its proapoptotic activity. Consistently, BRCA1 can counteract the
      proapoptotic activity of full-length BARD1 but not of BARD1beta. Several lines of
      evidence suggest that BARD1 is involved in proapoptotic signaling in testis: i)
      both BARD1 isoforms are mostly found in cells that stain positive for TUNEL, Bax,
      and activated caspase 3; ii) BARD1beta, capable of inducing apoptosis even in the
      presence of BRCA1, is specifically expressed in BRCA1-positive later stages of
      spermatogenesis; iii) antiapoptotic hormonal stimulation leads to BARD1
      downregulation; and iv) BARD1 expression is associated with human pathologies
      causing sterility due to increased germ cell death. Our data suggest that full
      length BARD1 might be involved in apoptotic control in spermatogonia and primary
      spermatocytes, while a switch to the BRCA1-independent BARD1beta might be
      necessary to induce apoptosis in BRCA1-expressing meiotic spermatocytes and early
      round spermatids.

PMID- 15240425
TI  - Implantation and pregnancy following in vitro fertilization and the effect of
      recombinant human relaxin administration in Macaca fascicularis.
AB  - Implantation and early pregnancy, and the potential effects of the reproductive
      hormone relaxin, were examined in the cynomolgus macaque (Macaca fascicularis)
      following in vitro fertilization and embryo transfer. Mature oocytes were
      collected from regularly cycling, female cynomolgus monkeys subjected to ovarian
      superovulation using recombinant human FSH and hCG. Oocytes fertilized in vitro
      were cultured to the 4- to 8-cell stage, slow-cooled, and stored in liquid
      nitrogen before thawing and embryo transfer. Regularly cycling recipients were
      administered recombinant human relaxin or vehicle for 21 days through the peri
      implantation period (Day 0 = pump implantation), during which time the thawed
      embryos were transferred (Day 7). Endometrial thickness and the number of
      gestational sacs were monitored by ultrasound at three time points (Days 7, 21,
      and 28). The number of days of placental sign (implantation bleeding) in pregnant
      females and menses in nonpregnant females were also recorded. Implantation
      (gestational sacs/embryo transferred) and multiple pregnancy (multiple
      gestations/ pregnant recipient) rates were slightly higher in relaxin-treated
      recipients compared to vehicle-treated recipients. Administration of relaxin was
      associated with increased implantation bleeding in pregnant females. Endometrial
      thickness was increased in relaxin-treated recipients at Days 7 and 28 compared
      to Day 0, but these differences were not observed at the same time points in
      vehicle-treated females. Systemic administration of recombinant human relaxin in
      an in vitro fertilization/embryo transfer setting was associated with effects
      consistent with a role for this hormone in endometrial physiology in primates.

PMID- 15240426
TI  - Gene transfer of inducible nitric oxide synthase complementary DNA regresses the
      fibrotic plaque in an animal model of Peyronie's disease.
AB  - The goal of the present study was to investigate the antifibrotic role of
      inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining
      whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can
      induce regression of the plaque. A PD-like plaque was induced with fibrin in the
      penile tunica albuginea of mice and then injected with a luciferase-expressing
      plasmid (pLuc), either alone or with piNOS, following luciferase expression in
      vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty
      control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in
      the absence of fibrin. Tissue sections were stained for collagen, transforming
      growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as
      profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of
      reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction
      with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido
      reductase (XOR; oxidative stress) were estimated by Western blot analysis.
      Luciferase reporter expression was restricted to the penis, peaked at 3 days
      after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS
      expression also peaked at 3 days, but expression decreased at the end of
      treatment, when a considerable reduction of plaque size occurred. Protein
      nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The
      piNOS gene transfer regressed the PD plaque and expression of profibrotic
      factors, supporting the view that endogenous iNOS induction in PD is defense
      mechanism by the tissue against fibrosis.

PMID- 15240427
TI  - Peroxiredoxin 6 is upregulated in bovine oocytes and cumulus cells during in
      vitro maturation: role of intercellular communication.
AB  - Peroxiredoxins are peroxidases involved in antioxidant defense and intracellular
      signaling. Expression of transcripts coding for peroxiredoxin 6 (PRDX6) has been
      previously described to be upregulated in oocytes after in vitro maturation, a
      period during which general transcription decreases dramatically in oocytes. The
      aim of the present work was to evaluate PRDX6 regulation in bovine cumulus-oocyte
      complexes in relation to maturation and intercellular communication. PRDX6
      expression was analyzed by reverse transcription-PCR and Western blotting in
      oocytes and cumulus cells before and after in vitro maturation. PRDX6 was found
      to be upregulated at the mRNA and protein levels in both cell types after
      maturation. The effect of paracrine and gap junctional communication on PRDX6
      expression was then assessed by culturing cumulus clusters in the presence or
      absence of denuded oocytes. While PRDX6 upregulation in oocytes required intact
      cumulus-oocyte junctions, the presence of denuded oocytes was necessary but
      sufficient for the upregulation to occur in cumulus cells. Finally, the influence
      of recombinant mouse growth differentiation factor-9 (GDF-9) on PRDX6 expression
      in cumulus cells was studied. GDF-9 induced cumulus expansion and PRDX6
      upregulation in bovine cumulus clusters. Altogether, our data suggest that PRDX6
      upregulation in cumulus-oocyte complexes during in vitro maturation is mutually
      regulated by both cell types: PRDX6 upregulation in oocytes would require gap
      junctions with cumulus cells, while upregulation in cumulus would depend on
      secretion of oocyte paracrine factor(s) with GDF-9 being a likely candidate.

PMID- 15240428
TI  - Matrix metalloproteinases and their tissue inhibitors in the developing neonatal
      mouse uterus.
AB  - Postnatal development of the mouse uterus involves differentiation and
      development of the endometrial glands as well as the myometrium. Matrix
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in
      extracellular matrix breakdown and morphogenesis of many epitheliomesenchymal
      organs. As a first step to understanding their roles in postnatal mouse uterine
      development, MMPs and TIMPs found to be expressed in the neonatal mouse uterus by
      microarray analysis were localized by in situ hybridization. The MMP-2 mRNA was
      detected only in the uterine stroma, whereas the MMP-10 mRNA was present only in
      the uterine epithelium from Postnatal Day (PND) 3 to PND 9. All other MMPs (MMP
      11, MMP-14, and MMP-23) as well as TIMP-1, TIMP-2, and TIMP-3 were detected in
      both epithelial and stromal cells of the endometrium, but not in the myometrium.
      Uterine extracts were then analyzed by gelatin and casein gel zymography to
      detect active gelatinases and stromelysins, respectively. Five major gelatinase
      bands of activity were detected and inhibited by the MMP inhibitors, EDTA or 1,10
      phenanthroline, but not by PMSF, a serine protease inhibitor. Western blot
      analysis confirmed the presence of MMP-2 and MMP-9 proteins in the uterus.
      Immunoreactive MMP-9 protein was detected only in the endometrial stroma, whereas
      immunoreactive MMP-2 protein was detected in both the stroma and epithelium of
      the uterus. Casein zymography detected three major bands of activity (
      approximately 54, 63, and 80 kDa) that were inhibited by the serine protease
      inhibitor, PMSF, but not by the MMP inhibitors, EDTA or 1,10-phenanthroline,
      suggesting that they were serine proteases. These results support the hypothesis
      that MMPs and TIMPs regulate postnatal development of the mouse uterus.

PMID- 15240429
TI  - Genomic imprinting of H19 in naturally reproduced and cloned cattle.
AB  - Animals produced from assisted reproductive technologies suffer from
      developmental abnormalities and early fetal death at a higher frequency than that
      observed in those produced by natural breeding. These symptoms are reminiscent of
      imprinting disruptions in the human and mouse, suggesting the possibility of
      perturbations in the expression of imprinted genes such as biallelic expression
      or silencing. H19 is one of the imprinted genes first identified in mice and
      humans, but its sequence and imprinting status have not been determined in
      cattle. In the present study, we obtained the majority of the bovine H19 gene
      sequence (approximately 2311 base pairs), identified a single nucleotide
      polymorphism (SNP) in exon 5 and determined the frequencies of different alleles
      containing the SNP. Our analysis demonstrated that, in cattle produced by natural
      breeding, H19 was indeed imprinted as shown by either predominant or exclusive
      expression of the maternal allele. We also analyzed the imprinting pattern of H19
      in organs of four animals produced by somatic cell nuclear transfer that died
      shortly after birth or had developed abnormalities that necessitated immediate
      killing at birth. Three out of four cloned animals showed biallelic expression of
      H19, supporting our hypothesis that imprinting disruption is present in cloned
      animals that suffered from developmental abnormalities at birth. Examination of
      the expression of H19 in the offspring of a cloned animal produced by artificial
      insemination showed that the imprinting pattern in this animal was
      indistinguishable from those of control animals, suggesting that either
      imprinting disruptions in cloned animals are corrected through natural
      reproduction or that they are not present in healthy cloned animals capable of
      undergoing natural reproduction.

PMID- 15240430
TI  - CLN3L, a novel protein related to the Batten disease protein, is overexpressed in
      Cln3-/- mice and in Batten disease.
AB  - Batten disease is a severe autosomal recessive neurodegenerative disease which
      results from mutations in CLN3. Although the gene was cloned in 1995, the tissue
      distribution and subcellular localization of the CLN3 protein (CLN3P) remains
      inconclusive. We have demonstrated the presence of a novel 33 kDa protein in both
      normal human and wild-type mouse brain. This 33 kDa protein, which is
      overexpressed in brains of patients with Batten disease and in Cln3-/- mouse
      brain, binds to the antibody raised against the peptide sequence of CLN3P and
      results in aberrant CLN3P localization studies. We expressed a novel 33 kDa
      protein that is highly similar to CLN3P. We showed that the 33 kDa protein is
      identical to that recognized in Batten disease and Cln3-/- brain. These studies
      strongly suggest the presence of an alternative CLN3-like (CLN3L) product in
      Batten disease. Previous studies of CLN3P tissue distribution and intracellular
      localization will require extensive reanalysis in order to determine the true
      expression of CLN3P.

PMID- 15240431
TI  - Brainstem neurodegeneration correlates with clinical dysfunction in SCA1 but not
      in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study.
AB  - Magnetic resonance (MR) techniques enable in vivo measurement of the atrophy of
      the brainstem and cerebellum in spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2)
      patients, which is accompanied by a decrease in the concentration of N-acetyl
      aspartate (NAA) or of the NAA/creatine ratio in the pons and cerebellum. Mean
      diffusivity (D) is emerging as an additional sensitive and quantitative MR
      parameter to investigate brain diseases. In order to explore differences between
      the MR features of SCA1 and SCA2 and correlate the MR and clinical findings in
      the two conditions, we examined 16 SCA1 patients, 12 SCA2 patients and 20 healthy
      control subjects. The MR protocol included T1-weighted 3D gradient echo
      sequences, single-voxel proton spectroscopy of the right cerebellar hemisphere
      (dentate and peridentate region) and of the pons with a PRESS sequence and an
      external reference quantitation method, and (in nine patients with SCA1 and nine
      patients with SCA2) diffusion-weighted echo-planar images with reconstruction of
      the D maps. The patients were evaluated with the Inherited Ataxia Clinical Rating
      Scale (IACRS). Compared with control subjects, the SCA1 and SCA2 patients showed
      a decrease (P < 0.01) in the volume of the brainstem and cerebellum and in the
      concentration of NAA in the pons and cerebellar hemisphere, whereas D of the
      brainstem and cerebellum was increased. No significant difference was observed
      between the SCA1 and SCA2 patient groups. No correlation between cerebellar
      volume and dentate and peridentate NAA concentration was found in SCA1 or SCA2
      patients. The volume of the brainstem, D of the brainstem and cerebellum and the
      concentration of NAA in the pons were correlated (P < 0.05) with the IACRS score
      in SCA1 but not in SCA2. This discrepancy is in line with the clinical
      observation that the clinical deficit has a later onset and faster progression in
      SCA1 and an earlier onset and slower progression in SCA2, and suggests that
      neurodegeneration of the brainstem is a comparatively more rapid process in SCA1.
      In conclusion, our study indicates that SCA1 and SCA2 substantially exhibit the
      same MR features. The correlation in SCA1 between clinical severity and
      quantitative volumetric, diffusion MRI and proton MR spectroscopy findings in the
      brainstem indicates that these measurements might be employed for longitudinal
      studies and hopefully as surrogate markers in future pharmacological trials of
      this condition.

PMID- 15240433
TI  - Do women really have more bilateral language representation than men? A meta
      analysis of functional imaging studies.
AB  - Sex differences in cognition are consistently reported, men excelling in most
      visuospatial tasks and women in certain verbal tasks. It has been hypothesized
      that these sex differences in cognition results from a more bilateral pattern of
      language representation in women than in men. This bilateral pattern of language
      representation in women is thought to interfere with visuospatial functions in
      the right hemisphere. To test whether language representation is indeed more
      bilateral in the female than in the male brain, a meta-analysis was performed on
      studies that assessed language activity with functional imaging in healthy men
      and women. Effect sizes were weighted for sample size and the meta-analytic
      method was applied to obtain a combined effect size. Fourteen studies were
      included, providing data on 377 men and 442 women. Meta-analysis yielded a mean
      weighted effect d of 0.21 with a 95% confidence interval of -0.05 to 0.48,
      indicating no significant difference in language lateralization between men and
      women. This implies that the putative sex difference in language lateralization
      may be absent at the population level, or may be observed only with some, as yet
      not defined, language tasks. It is therefore not likely that differences in
      language lateralization underlie the general sex differences in cognitive
      performance, and the neuronal basis for these cognitive sex differences remains
      elusive.

PMID- 15240432
TI  - Intra-operative mapping of cortical areas involved in reading in mono- and
      bilingual patients.
AB  - In order to identify the cortical areas involved in the reading process and to
      spare them during surgery, we systematically studied cortical areas by direct
      cortical stimulation in patients operated on for brain tumours. Seventy-six
      cortical stimulation mapping studies for language were performed in 35
      monolingual and 19 bi- or multilingual patients over a 5-year period. We
      systematically searched for reading interference areas in addition to standard
      naming areas using an 'awake surgery' technique for brain mapping. A 'reading
      aloud' task (translated into different languages in multilingual patients) was
      used. Brain mapping was performed in left (44 patients) and right (10 patients)
      hemispheres. Cortical areas involved in reading were identified according to the
      type of interference, location and distinctness from naming areas. Stimulation of
      several major hemispheric regions resulted in significant interference with
      reading aloud: (i) the lower part of the pre- and postcentral gyri (P < 0.00001);
      (ii) the dominant supramarginal, angular and the posterior part of the superior
      temporal gyri (P < 0.00001); (iii) in the dominant inferior and middle frontal
      gyri (P < 0.001); and (iv) in the posterior part of the dominant middle temporal
      gyrus (P < 0.05). Interferences in reading were generally found in small cortical
      areas, with intervening areas evoking no reading interferences. Only partial
      overlap between reading and naming sites was found. Reading-specific sites were
      preferentially found when stimulating dominant inferior parietal or posterior
      temporal areas. Different types of reading interferences were noted. While
      'articulatory' interferences were found in pre- and postcentral gyri bilaterally,
      and ocular-induced movements in bilateral middle frontal gyri, paraphasias were
      found mainly in the dominant supramarginal and posterior superior temporal gyri.
      Reading arrest sites were found in many regions. Reading interference sites were
      also occasionally found in the non-dominant hemisphere. In bilingual patients, if
      common cortical areas could be found, language- and reading-specific areas were
      sometimes detected, lending support to the concept that bilinguals can have
      relatively distinct cortical representation of their language skills. Finally, in
      this series, the location of reading interference sites and their relative
      specialization showed considerable individual variability.

PMID- 15240434
TI  - Functional consequences of hemispherectomy.
AB  - Using the International Classification of Functioning Disability and Health (ICF)
      (WHO, 2001), impairments, activities and social participation are reported in 12
      children (mean age at surgery 5.9 years) who were investigated before and three
      times over a 2-year period after hemispherectomy. Impairments were assessed (i)
      in terms of seizure frequency (Engel classification) and seizure severity (HASS)
      and (ii) with respect to muscle strength (MRC), range of motion (JAM score) and
      muscle tone (modified Ashworth scale). Activities were assessed in terms of gross
      motor functioning (GMFM) and self-care, mobility and social function (PEDI).
      Participation was assessed in terms of epilepsy-related restrictions and
      quantified by means of the Hague Restrictions in Childhood Epilepsy Scale
      (HARCES). Nine out of 12 children could be classified as free of seizures (Engel
      class I), and in the remaining three seizure frequency was Engel class III. HASS
      scores showed maximum improvement in 10 out of 12 children and near-maximum
      improvement in the two remaining children. Muscle strength and muscle tone on the
      side of the body contralateral to the hemispherectomy, which were already
      decreased preoperatively, decreased even further in the first 6 months after
      surgery, but returned to the presurgical baseline thereafter, except for the
      distal part of the arm. Range of motion was abnormal prior to operation and
      remained so after operation. Mean GMFM increase was 20% after 2 years (95%
      confidence interval 10-33); all five dimensions improved statistically
      significantly (P < 0.05). Mean PEDI increase was more than 20 scale points (95%
      confidence interval 10-35); again, all domains improved significantly (P < 0.05).
      In nearly all children, HARCES scores had normalized 2 years after surgery. In
      conclusion, decrease of seizure frequency and severity widens the scope of motor
      and social functioning, which overrides the effects of remaining motor
      impairments.

PMID- 15240435
TI  - Neural correlates of the chronic fatigue syndrome--an fMRI study.
AB  - Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of
      unknown aetiology. Patients who suffer from CFS report a variety of physical
      complaints as well as neuropsychological complaints. Therefore, it is conceivable
      that the CNS plays a role in the pathophysiology of CFS. The purpose of this
      study was to investigate neural correlates of CFS, and specifically whether there
      exists a linkage between disturbances in the motor system and CFS. We measured
      behavioural performance and cerebral activity using rapid event-related
      functional MRI in 16 CFS patients and 16 matched healthy controls while they were
      engaged in a motor imagery task and a control visual imagery task. CFS patients
      were considerably slower on performance of both tasks, but the increase in
      reaction time with increasing task load was similar between the groups. Both
      groups used largely overlapping neural resources. However, during the motor
      imagery task, CFS patients evoked stronger responses in visually related
      structures. Furthermore, there was a marked between-groups difference during
      erroneous performance. In both groups, dorsal anterior cingulate cortex was
      specifically activated during error trials. Conversely, ventral anterior
      cingulate cortex was active when healthy controls made an error, but remained
      inactive when CFS patients made an error. Our results support the notion that CFS
      may be associated with dysfunctional motor planning. Furthermore, the between
      groups differences observed during erroneous performance point to motivational
      disturbances as a crucial component of CFS.

PMID- 15240436
TI  - Assessing function and pathology in familial dysautonomia: assessment of
      temperature perception, sweating and cutaneous innervation.
AB  - This study was performed to assess cutaneous nerve fibre loss in conjunction with
      temperature and sweating dysfunction in familial dysautonomia (FD). In ten FD
      patients, we determined warm and cold thresholds at the calf and shoulder, and
      sweating in response to acetylcholine iontophoresis over the calf and forearm.
      Punch skin biopsies from calf and back were immunostained and imaged to assess
      nerve fibre density and neuropeptide content. Mean temperature thresholds and
      baseline sweat rate were elevated in the patients, while total sweat volume and
      response time did not differ from controls. The average density of epidermal
      nerve fibres was greatly diminished in the calf and back. There was also severe
      nerve loss from the subepidermal neural plexus (SNP) and deep dermis. The few
      sweat glands present within the biopsies had had reduced innervation density.
      Substance P immunoreactive (-ir) and calcitonin gene related peptide-ir (CGRP-ir)
      were virtually absent, but vasoactive intestinal peptide-ir (VIP-ir) nerves were
      present in the SNP. Empty Schwann cell sheaths were observed. Temperature
      perception was more impaired than sweating. Epidermal nerve fibre density was
      found to be profoundly reduced in FD. Decreased SP and CGRP-ir nerves suggest
      that the FD gene mutation causes secondary neurotransmitter depletions. Empty
      Schwann cell sheaths and VIP-ir nerves suggest active denervation and
      regeneration.

PMID- 15240437
TI  - Effects of subthalamic nucleus stimulation and medication on resting and postural
      tremor in Parkinson's disease.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and
      antiparkinsonian medication have proved to be effective treatments for tremor in
      Parkinson's disease. To date it is not known how and to what extent STN DBS alone
      and in combination with antiparkinsonian medication alters the pathophysiology of
      resting and postural tremor in idiopathic Parkinson's disease. The purpose of
      this study was to examine the effects of STN DBS and antiparkinsonian medication
      on the neurophysiological characteristics of resting and postural hand tremor in
      Parkinson's disease. Resting and postural hand tremor were recorded using
      accelerometry and surface electromyography (EMG) from 10 Parkinson's disease
      patients and 10 matched control subjects. The Parkinson's disease subjects were
      examined under four treatment conditions: (i) off treatment; (ii) STN DBS; (iii)
      medication; and (iv) medication plus STN DBS. The amplitude, EMG frequency,
      regularity, and 1-8 Hz tremor-EMG coherence were analysed. Both STN DBS and
      medication reduced the amplitude, regularity and tremor-EMG coherence, and
      increased the EMG frequency of resting and postural tremor in Parkinson's
      disease. STN DBS was more effective than medication in reducing the amplitude and
      increasing the frequency of resting and postural tremor to healthy physiological
      levels. These findings provide strong evidence that effective STN DBS normalizes
      the amplitude and frequency of tremor. The findings suggest that neural activity
      in the STN is an important modulator of the neural network(s) responsible for
      both resting and postural tremor genesis in Parkinson's disease.

PMID- 15240438
TI  - Effect of joint crisis plans on use of compulsory treatment in psychiatry: single
      blind randomised controlled trial.
AB  - OBJECTIVE: To investigate whether a form of advance agreement for people with
      severe mental illness can reduce the use of inpatient services and compulsory
      admission or treatment. DESIGN: Single blind randomised controlled trial, with
      randomisation of individual patients. The investigator was blind to allocation.
      SETTING: Eight community mental health teams in southern England. PARTICIPANTS:
      160 people with an operational diagnosis of psychotic illness or non-psychotic
      bipolar disorder who had experienced a hospital admission within the previous two
      years. INTERVENTION: The joint crisis plan was formulated by the patient, care
      coordinator, psychiatrist, and project worker and contained contact information,
      details of mental and physical illnesses, treatments, indicators for relapse, and
      advance statements of preferences for care in the event of future relapse. MAIN
      OUTCOME MEASURES: Admission to hospital, bed days, and use of the Mental Health
      Act over 15 month follow up. RESULTS: Use of the Mental Health Act was
      significantly reduced for the intervention group, 13% (10/80) of whom experienced
      compulsory admission or treatment compared with 27% (21/80) of the control group
      (risk ratio 0.48, 95% confidence interval 0.24 to 0.95, P = 0.028). As a
      consequence, the mean number of days of detention (days spent as an inpatient
      while under a section of the Mental Health Act) for the whole intervention group
      was 14 compared with 31 for the control group (difference 16, 0 to 36, P = 0.04).
      For those admitted under a section of the Mental Health Act, the number of days
      of detention was similar in the two groups (means 114 and 117, difference 3, -61
      to 67, P = 0.98). The intervention group had fewer admissions (risk ratio 0.69,
      0.45 to 1.04, P = 0.07). There was no evidence for differences in bed days (total
      number of days spent as an inpatient) (means 32 and 36, difference 4, -18 to 26,
      P = 0.15 for the whole sample; means 107 and 83, difference -24, -72 to 24, P =
      0.39 for those admitted). CONCLUSIONS: Use of joint crisis plans reduced
      compulsory admissions and treatment in patients with severe mental illness. The
      reduction in overall admission was less. This is the first structured clinical
      intervention that seems to reduce compulsory admission and treatment in mental
      health services.

PMID- 15240439
TI  - Computer simulation of small molecule permeation across a lipid bilayer:
      dependence on bilayer properties and solute volume, size, and cross-sectional
      area.
AB  - Cell membrane permeation is required for most drugs to reach their biological
      target, and understanding this process is therefore crucial for rational drug
      design. Recent molecular dynamics simulations have studied the permeation of
      eight small molecules through a phospholipid bilayer. Unlike experiments,
      atomistic simulations allow the direct calculation of diffusion and partition
      coefficients of solutes at different depths inside a lipid membrane. Further
      analyses of the simulations suggest that solute diffusion is less size-dependent
      and solute partitioning more size-dependent than was commonly thought.

PMID- 15240440
TI  - Bilayer conformation of fusion peptide of influenza virus hemagglutinin: a
      molecular dynamics simulation study.
AB  - Unraveling the conformation of membrane-bound viral fusion peptides is essential
      for understanding how those peptides destabilize the bilayer topology of lipids
      that is important for virus-cell membrane fusion. Here, molecular dynamics (MD)
      simulations were performed to investigate the conformation of the 20 amino acids
      long fusion peptide of influenza hemagglutinin of strain X31 bound to a
      dimyristoyl phosphatidylcholine (DMPC) bilayer. The simulations revealed that the
      peptide adopts a kinked conformation, in agreement with the NMR structures of a
      related peptide in detergent micelles. The peptide is located at the amphipathic
      interface between the headgroups and hydrocarbon chains of the lipid by an
      energetically favorable arrangement: The hydrophobic side chains of the peptides
      are embedded into the hydrophobic region and the hydrophilic side chains are in
      the headgroup region. The N-terminus of the peptide is localized close to the
      amphipathic interface. The molecular dynamics simulations also revealed that the
      peptide affects the surrounding bilayer structure. The average hydrophobic
      thickness of the lipid phase close to the N-terminus is reduced in comparison
      with the average hydrophobic thickness of a pure dimyristoyl phosphatidylcholine
      bilayer.

PMID- 15240441
TI  - On the theory of noncovalent binding.
AB  - It is widely accepted that the binding constant of a receptor and ligand can be
      written as a two-body integral involving the interaction energy of the receptor
      and the ligand. Interestingly, however, three different theories of binding in
      the literature dictate three distinct integrals. The present study uses theory,
      as well as simulations of binding experiments, to test the validity of the three
      integrals. When binding is measured by a signal that detects the ligand in the
      binding site, the most accurate results are obtained by an integral of the
      Boltzmann factor, where the bound complex is defined in terms of an exclusive
      binding region. A novel prediction of this approach, that expanding a ligand can
      increase its binding constant, is borne out by the simulations. The simulations
      also show that abnormal binding isotherms can be obtained when the region over
      which the signal is detected deviates markedly from the exclusion zone.
      Interestingly, the binding constant measured by equilibrium dialysis, rather than
      by monitoring a localized signal, can yield a binding constant that differs from
      that obtained from a signal measurement, and that is matched best by the integral
      of the Mayer factor.

PMID- 15240442
TI  - The JAK-STAT signaling network in the human B-cell: an extreme signaling pathway
      analysis.
AB  - Large-scale models of signaling networks are beginning to be reconstructed and
      corresponding analysis frameworks are being developed. Herein, a reconstruction
      of the JAK-STAT signaling system in the human B-cell is described and a scalable
      framework for its network analysis is presented. This approach is called extreme
      signaling pathway analysis and involves the description of network properties
      with systemically independent basis vectors called extreme pathways. From the
      extreme signaling pathways, emergent systems properties of the JAK-STAT signaling
      network have been characterized, including 1), a mathematical definition of
      network crosstalk; 2), an analysis of redundancy in signaling inputs and outputs;
      3), a study of reaction participation in the network; and 4), a delineation of 85
      correlated reaction sets, or systemic signaling modules. This study is the first
      such analysis of an actual biological signaling system. Extreme signaling pathway
      analysis is a topologically based approach and assumes a balanced use of the
      signaling network. As large-scale reconstructions of signaling networks emerge,
      such scalable analyses will lead to a description of the fundamental systems
      properties of signal transduction networks.

PMID- 15240443
TI  - Determination of a unique solution to parallel proton transfer reactions using
      the genetic algorithm.
AB  - Kinetic analysis of the dynamics as measured in multiequilibria systems is
      readily attained by curve-fitting methodologies, a treatment that can accurately
      retrace the shape of the measured signal. Still, these reconstructions are not
      related to the detailed mechanism of the process. In this study we subjected
      multiple proton transfer reactions to rigorous kinetic analysis, which consists
      of solving a set of coupled-nonlinear differential rate equations. The manual
      analysis of such systems can be biased by the operator; thus the analysis calls
      for impartial corroboration. What is more, there is no assurance that such a
      complex system has a unique solution. In this study, we used the Genetic
      Algorithm to investigate whether the solution of the system will converge into a
      single global minimum in the multidimensional parameter space. The experimental
      system consisted of proton transfer between four proton-binding sites with seven
      independent adjustable parameters. The results of the search indicate that the
      solution is unique and all adjustable parameters converge into a single minimum
      in the multidimensional parameter space, thus corroborating the accuracy of the
      manual analysis.

PMID- 15240444
TI  - Microscopic Mechanism of Antibiotics Translocation through a Porin.
AB  - OmpF from the outer membrane of Escherichia coli is a general porin considered to
      be the main pathway for beta-lactam antibiotics. The availability of a high
      resolution crystal structure of OmpF and new experimental techniques at the
      single-molecule level have opened the way to the investigation of the microscopic
      mechanisms that allow the passage of antibiotics through bacterial pores. We
      applied molecular dynamics simulations to investigate the translocation process
      of ampicillin (Amp) through OmpF. Using a recent algorithm capable of
      accelerating molecular dynamics simulations we have been able to obtain a
      reaction path for the translocation of Amp through OmpF. The mechanism of passage
      depends both on the internal degrees of freedom of Amp and on interactions of Amp
      with OmpF. Understanding this mechanism would help us design more efficient
      antibiotics and shed light on nature's way of devising channels able to enhance
      the transport of molecules through membranes.

PMID- 15240445
TI  - A Brownian dynamics study: the effect of a membrane environment on an electron
      transfer system.
AB  - During the past few years, three-dimensional crystal structures of many of the
      important integral membrane proteins responsible for the bioenergetic processes
      of photosynthesis and respiration have been determined. Moreover, a few crystal
      structures of protein-protein complexes have become available that characterize
      the interaction between those membrane proteins and the electron carrier protein
      cytochrome c. Here, we address the association kinetics for binding of cytochrome
      c to cytochrome c oxidase (COX) from Paracoccus denitrificans by Brownian
      dynamics simulations. The effects of ionic strength and protein mutations were
      studied for two different cytochrome c species: the positively charged, dipolar
      horse heart cytochrome c and the negatively charged physiological electron
      transfer partner cytochrome c(552). We studied association toward "naked" COX and
      toward membrane-embedded COX where the membrane is represented as an uncharged
      DPPC bilayer modeled in atomistic detail. For the nonnatural association toward
      "naked" COX, the association rates are >100 times larger for horse heart
      cytochrome c than for cytochrome c(552). Interestingly, the presence of the lipid
      bilayer leads to a dramatic decrease of the association rate of horse heart
      cytochrome c, but slightly enhances association of cytochrome c(552), leading to
      very similar association rates of both proteins to membrane-embedded COX. This
      finding from computational modeling studies may reflect the optimization of
      surface patches and of the total net charge on electron transfer pairs in nature.

PMID- 15240446
TI  - Localization and extinction of bacterial populations under inhomogeneous growth
      conditions.
AB  - The transition from localized to systemic spreading of bacteria, viruses, and
      other agents is a fundamental problem that spans medicine, ecology, biology, and
      agriculture science. We have conducted experiments and simulations in a simple
      one-dimensional system to determine the spreading of bacterial populations that
      occurs for an inhomogeneous environment under the influence of external
      convection. Our system consists of a long channel with growth inhibited by
      uniform ultraviolet (UV) illumination except in a small "oasis", which is
      shielded from the UV light. To mimic blood flow or other flow past a localized
      infection, the oasis is moved with a constant velocity through the UV-illuminated
      "desert". The experiments are modeled with a convective reaction-diffusion
      equation. In both the experiment and model, localized or extinct populations are
      found to develop, depending on conditions, from an initially localized
      population. The model also yields states where the population grows everywhere.
      Further, the model reveals that the transitions between localized, extended, and
      extinct states are continuous and nonhysteretic. However, it does not capture the
      oscillations of the localized population that are observed in the experiment.

PMID- 15240447
TI  - Calcium dynamics in dendritic spines and spine motility.
AB  - A dendritic spine is an intracellular compartment in synapses of central neurons.
      The role of the fast twitching of spines, brought about by a transient rise of
      internal calcium concentration above that of the parent dendrite, has been
      hitherto unclear. We propose an explanation of the cause and effect of the
      twitching and its role in the functioning of the spine as a fast calcium
      compartment. Our molecular model postulates that rapid spine motility is due to
      the concerted contraction of calcium-binding proteins. The contraction induces a
      stream of cytoplasmic fluid in the direction of the dendritic shaft, thus
      speeding up the time course of spine calcium dynamics, relative to pure
      diffusion. Simulations indicate that chemical reaction rate theory at the
      molecular level can explain spine motility. They reveal two time periods in
      calcium dynamics, as measured recently by other researchers. It appears that
      rapid motility in dendritic spines increases the efficiency of calcium conduction
      to the dendrite and speeds up the emptying of the spine. This could play a major
      role in the induction of synaptic plasticity. A prediction of the model is that
      alteration of spine motility will modify the time course of calcium in the
      dendritic spine and could be tested experimentally.

PMID- 15240448
TI  - Ca2+ dynamics in a population of smooth muscle cells: modeling the recruitment
      and synchronization.
AB  - Many experimental studies have shown that arterial smooth muscle cells respond
      with cytosolic calcium rises to vasoconstrictor stimulation. A low
      vasoconstrictor concentration gives rise to asynchronous spikes in the calcium
      concentration in a few cells (asynchronous flashing). With a greater
      vasoconstrictor concentration, the number of smooth muscle cells responding in
      this way increases (recruitment) and calcium oscillations may appear. These
      oscillations may eventually synchronize and generate arterial contraction and
      vasomotion. We show that these phenomena of recruitment and synchronization
      naturally emerge from a model of a population of smooth muscle cells coupled
      through their gap junctions. The effects of electrical, calcium, and inositol
      1,4,5-trisphosphate coupling are studied. A weak calcium coupling is crucial to
      obtain a synchronization of calcium oscillations and the minimal required calcium
      permeability is deduced. Moreover, we note that an electrical coupling can
      generate oscillations, but also has a desynchronizing effect. Inositol 1,4,5
      trisphosphate diffusion does not play an important role to achieve
      synchronization. Our model is validated by published in vitro experiments
      obtained on rat mesenteric arterial segments.

PMID- 15240449
TI  - Simulation of the interaction between ScyTx and small conductance calcium
      activated potassium channel by docking and MM-PBSA.
AB  - Computational methods are employed to simulate interaction of scorpion toxin
      ScyTx in complex with the small conductance calcium-activated potassium channel
      rsk2. All of available 25 structures of ScyTx in the Protein Data Bank determined
      by NMR were considered for improving performance of rigid protein docking of
      ZDOCK. Four main binding modes were found among a large number of predicted
      complexes by using clustering analysis, screening with expert knowledge, energy
      minimization, and molecular dynamics simulations. The quality and validity of the
      resulting complexes were further evaluated by molecular dynamics simulations with
      the generalized Born solvation model and by calculation of relative binding free
      energies with the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) in
      the AMBER 7 suit of programs. The complex formed by the 22nd structure of the
      ScyTx and rsk2 channel was identified as the most favorable complex by using a
      combination of computational methods, which contain further introduction of
      flexibility without restraining residue side chain. From the resulted spatial
      structure of the ScyTx and rsk2 channel, ScyTx associates the mouth of the rsk2
      channel with alpha-helix rather than beta-sheet. Structural analysis first
      revealed that Arg(13) played a novel and vital role of blocking the pore of the
      rsk2 channel, whose role is remarkably different from that of highly homologous
      scorpion toxin P05. Between the interfaces in the ScyTx-rsk2 complex, strong
      electrostatic interaction and hydrogen bonds exist between Arg(13) of ScyTx and
      Gly-Tyr-Gly-Asp sequential residues located in the four symmetrical chains of the
      pore region. Simultaneously, five hydrogen bonds between Arg(6) of ScyTx and
      Asp(341)(C), Val(366)(C), and Pro(367)(C), and electrostatic interaction between
      Arg(6) of ScyTx and Asp(364)(B) and Asp(341)(C) are also found by structural
      analysis. In addition, His(31) located at the C-terminal of ScyTx is surrounded
      by Val(342)(A), Asp(364)(A), Met(365)(A), Pro(367)(B), and Asn(366)(B) within a
      contact distance of 4.0 A. These simulation results are in good agreement with
      experimental data and can effectively explain the binding phenomena between ScyTx
      and the potassium channel at the level of molecular spatial structure. The
      consistency between results of molecular modeling and experimental data strongly
      suggests that our spatial structure model of the ScyTx-rsk2 complex is
      reasonable. Therefore, molecular docking combined with molecular dynamics
      simulations followed by molecular mechanics Poisson-Boltzmann surface area
      analysis is an attractive approach for modeling scorpion toxin-potassium channel
      complexes a priori for further biological studies.

PMID- 15240451
TI  - Water movement during ligand unbinding from receptor site.
AB  - An 1-ns unbinding trajectory of retinol from the bovine serum retinol-binding
      protein has been obtained from molecular dynamics simulations. The behavior of
      water during ligand unbinding has never been studied in detail. I described a new
      method for defining a binding site, located the water molecules involved in the
      binding site, and examined their movements during unbinding. I found that there
      were only small changes in the binding site. During unbinding, the number of
      water molecules inside the binding site decreased, with some water molecules
      exhibiting movements similar in magnitude to bulk water, and there were
      rearrangements of the hydrogen bonds. This work represents the first detailed
      study of the behavior of water during an unbinding process.

PMID- 15240450
TI  - Distributions in protein conformation space: implications for structure
      prediction and entropy.
AB  - By considering how polymer structures are distributed in conformation space, we
      show that it is possible to quantify the difficulty of structural prediction and
      to provide a measure of progress for prediction calculations. The critical issue
      is the probability that a conformation is found within a specified distance of
      another conformer. We address this question by constructing a cumulative
      distribution function (CDF) for the average probability from observations about
      its limiting behavior at small displacements and numerical simulations of
      polyalanine chains. We can use the CDF to estimate the likelihood that a
      structure prediction is better than random chance. For example, the chance of
      randomly predicting the native backbone structure of a 150-amino-acid protein to
      low resolution, say within 6 A, is 10(-14). A high-resolution structural
      prediction, say to 2 A, is immensely more difficult (10(-57)). With additional
      assumptions, the CDF yields the conformational entropy of protein folding from
      native-state coordinate variance. Or, using values of the conformational entropy
      change on folding, we can estimate the native state's conformational span. For
      example, for a 150-mer protein, equilibrium alpha-carbon displacements in the
      native ensemble would be 0.3-0.5 A based on T Delta S of 1.42 kcal/(mol residue).

PMID- 15240452
TI  - How environment supports a state: molecular dynamics simulations of two states in
      bacteriorhodopsin suggest lipid and water compensation.
AB  - The light-driven proton pump bacteriorhodopsin (bR) is a transmembrane protein
      that uses large conformational changes for proton transfer from the cytoplasmic
      to the extracellular regions. Crystal structures, due to their solvent
      conditions, do not resolve the effect of lipid molecules on these protein
      conformational changes. To begin to understand the molecular details behind such
      large conformational changes, we simulated two conformations of wild-type
      bacteriorhodopsin, one of the dark-adapted state and the second of an
      intermediate (M(O)) state, each within an explicit dimyristoyl
      phosphatidylcholine (DMPC) lipid bilayer. The simulations included all-hydrogen
      and all-atom representations of protein, lipid, and water and were performed for
      20 ns. We investigate the equilibrium properties and the dynamic motions of the
      two conformations in the lipid setting. We note that the conformational state of
      the M(O) intermediate bR remains markedly different from the dark-adapted bR
      state in that the M(O) intermediate shows rearrangement of the cytoplasmic
      portions of helices C, F, and G, and nearby loops. This difference in the states
      remained throughout the simulations, and the results are stable on the molecular
      dynamics timescale and provide an illustration of the changes in both lipid and
      water that help to stabilize a particular state. Our analysis focuses on how the
      environment adjusts to these two states and on how the dynamics of the helices,
      loops, and water molecules can be related to the pump mechanism of
      bacteriorhodopsin. For example, water generally behaves in the same manner on the
      extracellular sides of both simulations but is decreased in the cytoplasmic
      region of the M(O) intermediate. We suspect that the different water behavior is
      closely related to the fluctuations of microcavities volume in the protein
      interior, which is strongly coupled to the collective motion of the protein. Our
      simulation result suggests that experimental observation can be useful to verify
      a decreased number of waters in the cytoplasmic regions of the late-intermediate
      stages by measuring the rate of water exchange with the interior of the protein.

PMID- 15240453
TI  - The stability and dynamics of the human calcitonin amyloid peptide DFNKF.
AB  - The stability and dynamics of the human calcitonin-derived peptide DFNKF (hCT(15
      19)) are studied using molecular dynamics (MD) simulations. Experimentally, this
      peptide is highly amyloidogenic and forms fibrils similar to the full length
      calcitonin. Previous comparative MD studies have found that the parallel beta
      stranded sheet is a stable organization of the DFNKF protofibril. Here, we probe
      the stability and dynamics of the small parallel DFNKF oligomers. The results
      show that even small DFNKF oligomers, such as trimers and tetramers, are stable
      for a sufficient time in the MD simulations, indicating that the crucial nucleus
      seed size for amyloid formation can be quite small. The simulations also show
      that the stability of DFNKF oligomers increases with their sizes. The small but
      stable seed may reflect the experimental rapid formation of the DFNKF fibrils.
      Further, a noncooperative process of parallel beta-sheet formation from the out
      of-register trimer is observed in the simulations. In general, the residues of
      DFNKF peptides near the N-/C-termini are more flexible, whereas the interior
      residues are more stable. Simulations of mutants and capped peptides show that
      both interstrand hydrophobic and electrostatic interactions play important roles
      in stabilizing the DFNKF parallel oligomers. This study provides insights into
      amyloid formation.

PMID- 15240454
TI  - Modeling noncompetitive antagonism of a nicotinic acetylcholine receptor.
AB  - Models of closed and open channel pores of a muscle-type nicotinic acetylcholine
      receptor (nAChR) channel comprising M1 and M2 segments are presented. A model of
      the closed channel is proposed in which hydrophobic residues of the Equatorial
      Leucine ring screen the oxygen domain formed by the Serine ring, thereby
      preventing ion flux without completely occluding the pore. This model
      demonstrates a high similarity with the structure derived from a recent electron
      microscopy study. We propose that hydrophobic residues of the Equatorial Leucine
      ring are retracted when the pore is open. Our models provide a possible
      resolution of the nAChR gate controversy. We have also obtained explanations for
      the complex mechanisms underlying inhibition of nAChR by philanthotoxins (PhTXs).
      PhTX-343, containing a spermine moiety with a charge of +3, binds deep in the
      pore near the Serine ring where classical open channel blockers of nAChR bind. In
      contrast, PhTX-(12), which has a single charged amino group is unable to reach
      deeply located rings because of steric restrictions. Both philanthotoxins may
      bind to a hydrophobic site located close to the external entrance of the pore in
      a region that includes residues associated with the regulation of
      desensitization.

PMID- 15240455
TI  - Database-derived potentials dependent on protein size for in silico folding and
      design.
AB  - Knowledge-based potentials are widely used in simulations of protein folding,
      structure prediction, and protein design. Their advantages include limited
      computational requirements and the ability to deal with low-resolution protein
      models compatible with long-scale simulations. Their drawbacks comprehend their
      dependence on specific features of the dataset from which they are derived, such
      as the size of the proteins it contains, and their physical meaning is still a
      subject of debate. We address these issues by probing the theoretical validity of
      these potentials as mean-force potentials that take the solvent implicitly into
      account and involve entropic contributions due to atomic degrees of freedom and
      solvation. The dependence on the size of the system is checked on distance
      dependent amino acid pair potentials, derived from six protein structure sets
      containing proteins of increasing length N. For large inter-residue distances,
      they are found to display the theoretically predicted 1/N behavior weighted by a
      factor depending on the boundaries and the compressibility of the system. For
      short distances, different trends are observed according to the nature of the
      residue pairs and their ability to form, for example, electrostatic, cation-pi or
      pi-pi interactions, or hydrophobic packing. The results of this analysis are used
      to devise a novel protein size-dependent distance potential, which displays an
      improved performance in discriminating native sequence-structure matches among
      decoy models.

PMID- 15240456
TI  - Molecular dynamics simulations of the lipid bilayer edge.
AB  - Phospholipid bilayers have been intensively studied by molecular dynamics (MD)
      simulation in recent years. The properties of bilayer edges are important in
      determining the structure and stability of pores formed in vesicles and
      biomembranes. In this work, we use molecular dynamics simulation to investigate
      the structure, dynamics, and line tension of the edges of bilayer ribbons
      composed of pure dimyristoylphosphatidylcholine (DMPC) or palmitoyl
      oleoylphosphatidylethanolamine (POPE). As expected, we observe a significant
      reorganization of lipids at and near the edges. The treatment of electrostatic
      effects is shown to have a qualitative impact on the structure and stability of
      the edge, and significant differences are observed in the dynamics and structure
      of edges formed by DMPC and palmitoyl-oleoylphosphatidylethanolamine. From the
      pressure anisotropy in the simulation box, we calculate a line tension of
      approximately 10-30 pN for the DMPC edge, in qualitative agreement with
      experimental estimates for similar lipids.

PMID- 15240458
TI  - Variations in the fast folding rates of the lambda-repressor: a hybrid molecular
      dynamics study.
AB  - The ability to predict the effects of mutations on protein folding rates and
      mechanisms would greatly facilitate folding studies. Using a realistic full atom
      potential coupled with a Go-like potential biased to the native state structure,
      we have investigated the effects of point mutations on the folding rates of a
      small single domain protein. The hybrid potential provides a detailed level of
      description of the folding mechanism that we correlate to features of the folding
      energy landscapes of fast and slow mutants of an 80-residue-long fragment of the
      lambda-repressor. Our computational reconstruction of the folding events is
      compared to the recent experimental results of W. Y. Yang and M. Gruebele (see
      companion article) and T. G. Oas and co-workers on the lambda-repressor, and
      helps to clarify the differences observed in the folding mechanisms of the
      various mutants.

PMID- 15240457
TI  - Three roads to islet bursting: emergent oscillations in coupled phantom bursters.
AB  - Glucose-induced membrane potential and Ca(2+) oscillations in isolated pancreatic
      beta-cells occur over a wide range of frequencies, from >6/min (fast) to <1/min
      (slow). However, cells within intact islets generally oscillate with periods of
      10-60 s (medium). The phantom bursting concept addresses how beta-cells can
      generate such a wide range of frequencies. Here, we explore an updated phantom
      bursting model to determine how heterogeneity in a single parameter can explain
      both the broad frequency range observed in single cells and the rarity of medium
      oscillations. We then incorporate the single-cell model into an islet model with
      parameter heterogeneity. We show that strongly coupled islets must be composed of
      predominantly medium oscillating single cells or a mixture of fast and slow cells
      to robustly produce medium oscillations. Surprisingly, we find that this
      constraint does not hold for moderate coupling, and that robustly medium
      oscillating islets can arise from populations of single cells that are
      essentially all slow or all fast. Thus, with coupled phantom bursters, medium
      oscillating islets can be constructed out of cells that are either all fast, all
      slow, or a combination of the two.

PMID- 15240459
TI  - Prediction of hybridization and melting for double-stranded nucleic acids.
AB  - This article presents a general statistical mechanical approach to describe self
      folding together with the hybridization between a pair of finite length DNA or
      RNA molecules. The model takes into account the entire ensemble of single- and
      double-stranded species in solution and their mole fractions at different
      temperatures. The folding and hybridization models deal with matched pairs,
      mismatches, symmetric and asymmetric interior loops, bulges, and single-base
      stacking that might exist at duplex ends or at the ends of helices. All possible
      conformations of the single- and double-stranded species are explored. Only
      intermolecular basepairs are considered in duplexes at this stage.In particular
      we focus on the role of stacking between neighboring nucleotide residues of
      single unfolded strands as an important source of enthalpy change on helix
      formation which has not been modeled computationally thus far. Changes in the
      states of the single strands with temperature are shown to lead to a larger heat
      effect at higher temperature. An important consequence of this is that
      predictions of enthalpies, which are based on databases of nearest-neighbor
      energy parameters determined for molecules or duplexes with lower melting
      temperatures compared with the melting temperatures of the oligos for which they
      are used as a predictive tool, will be underestimated.

PMID- 15240460
TI  - Molecular dynamics simulations of Guanine quadruplex loops: advances and force
      field limitations.
AB  - A computational analysis of d(GGGGTTTTGGGG)(2) guanine quadruplexes containing
      either lateral or diagonal four-thymidine loops was carried out using molecular
      dynamics (MD) simulations in explicit solvent, locally enhanced sampling (LES)
      simulations, systematic conformational search, and free energy molecular
      mechanics, Poisson Boltzmann, surface area (MM-PBSA) calculations with explicit
      inclusion of structural monovalent cations. The study provides, within the
      approximations of the applied all-atom additive force field, a qualitatively
      complete analysis of the available loop conformational space. The results are
      independent of the starting structures. Major conformational transitions not seen
      in conventional MD simulations are observed when LES is applied. The favored LES
      structures consistently provide lower free energies (as estimated by molecular
      mechanics, Poisson Boltzmann, surface area) than other structures. Unfortunately,
      the predicted optimal structure for the diagonal loop arrangement differs
      substantially from the atomic resolution experiments. This result is attributed
      to force field deficiencies, such as the potential misbalance between solute
      cation and solvent-cation terms. The MD simulations are unable to maintain the
      stable coordination of the monovalent cations inside the diagonal loops as
      reported in a recent x-ray study. The optimal diagonal and lateral loop
      arrangements appear to be close in energy although a proper inclusion of the loop
      monovalent cations could stabilize the diagonal architecture.

PMID- 15240461
TI  - Effects of ryanoids on spontaneous and depolarization-evoked calcium release
      events in frog muscle.
AB  - The effects of ryanoids on calcium sparks and transients were studied in voltage
      clamped cut frog muscle fibers with a laser scanning confocal microscope. For
      each ryanoid employed, several sequential effects were observed, including: a),
      transient increases in spontaneous spark frequency; b), conversions of sparks to
      long-lasting steady glows; and c), occasional interruptions of the glows. The
      ratio of the amplitude of the glow induced by a ryanoid to that of the precursory
      spark followed the order: ryanodol > ryanodine > C(10)-O(eq)-glycyl-ryanodine >
      C(10)-O(eq)-beta-alanyl-ryanodol. This sequence of glow amplitudes parallels that
      of the subconductances induced by these ryanoids in single-channel studies,
      suggesting that the glows reflect Ca(2+) fluxes through semiopen calcium release
      channels. Ryanoids also abolished depolarization-evoked sparks elicited with
      small pulses, and transformed the calcium release during depolarization to a
      uniform nonsparking fluorescence signal. The ratio of this signal, averaged
      spatially, to that of the control followed the order: ryanodol < ryanodine <
      C(10)-O(eq)-glycyl-ryanodine < C(10)-O(eq)-beta-alanyl-ryanodol, implying an
      inverse relationship with the amplitudes of ryanoid-induced glows. The
      observation that depolarization-evoked calcium release can occur after ryanoid
      suppression of calcium sparks suggests the possibility of a new strategic
      approach for treating skeletal muscle diseases resulting from leaky calcium
      release channels.

PMID- 15240462
TI  - Filter flexibility and distortion in a bacterial inward rectifier K+ channel:
      simulation studies of KirBac1.1.
AB  - The bacterial channel KirBac1.1 provides a structural homolog of mammalian inward
      rectifier potassium (Kir) channels. The conformational dynamics of the
      selectivity filter of Kir channels are of some interest in the context of
      possible permeation and gating mechanisms for this channel. Molecular dynamics
      simulations of KirBac have been performed on a 10-ns timescale, i.e., comparable
      to that of ion permeation. The results of five simulations (total simulation time
      50 ns) based on three different initial ion configurations and two different
      model membranes are reported. These simulation data provide evidence for limited
      (<0.1 nm) filter flexibility during the concerted motion of ions and water
      molecules within the filter, such local changes in conformation occurring on an
      approximately 1-ns timescale. In the absence of K(+) ions, the KirBac selectivity
      filter undergoes more substantial distortions. These resemble those seen in
      comparable simulations of other channels (e.g., KcsA and KcsA-based homology
      models) and are likely to lead to functional closure of the channel. This
      suggests filter distortions may provide a mechanism of K-channel gating in
      addition to changes in the hydrophobic gate formed at the intracellular crossing
      point of the M2 helices. The simulation data also provide evidence for
      interactions of the "slide" (pre-M1) helix of KirBac with phospholipid
      headgroups.

PMID- 15240463
TI  - Calcium-dependent facilitation and graded deactivation of store-operated calcium
      entry in fetal skeletal muscle.
AB  - Activation of store-operated Ca(2+) entry (SOCE) into the cytoplasm requires
      retrograde signaling from the intracellular Ca(2+) release machinery, a process
      that involves an intimate interaction between protein components on the
      intracellular and cell surface membranes. The cellular machinery that governs the
      Ca(2+) movement in muscle cells is developmentally regulated, reflecting
      maturation of the junctional membrane structure as well as coordinated expression
      of related Ca(2+) signaling molecules. Here we demonstrate the existence of SOCE
      in freshly isolated skeletal muscle cells obtained from embryonic days 15 and 16
      of the mouse embryo, a critical stage of muscle development. SOCE in the fetal
      muscle deactivates incrementally with the uptake of Ca(2+) into the sarcoplasmic
      reticulum (SR). A novel Ca(2+)-dependent facilitation of SOCE is observed in
      cells transiently exposed to high cytosolic Ca(2+). Our data suggest that
      cytosolic Ca(2+) can facilitate SOCE whereas SR luminal Ca(2+) can deactivate
      SOCE in the fetal skeletal muscle. This cooperative mechanism of SOCE regulation
      by Ca(2+) ions not only enables tight control of SOCE by the SR membrane, but
      also provides an efficient mechanism of extracellular Ca(2+) entry in response to
      physiological demand. Such Ca(2+) signaling mechanism would likely contribute to
      contraction and development of the fetal skeletal muscle.

PMID- 15240464
TI  - Use of the covariance matrix in directly fitting kinetic parameters: application
      to GABAA receptors.
AB  - A new method of analysis is described that begins to explore the relationship
      between the phases of ion channel desensitization and the underlying states of
      the channel. The method, referred to as covariance fitting (CVF), couples Q
      matrix calculations with a maximum likelihood algorithm to fit macroscopic
      desensitization data directly to kinetic models. Unlike conventional sum-of
      squares minimization, CVF fits both the magnitude of the recorded current and the
      strength of the correlations between different time points. When applied to
      simulated data generated using various kinetic models with up to 11 free
      parameters, CVF leads to reasonable parameter estimates. Coupled with the
      likelihood ratio test, it accurately discriminates between models with different
      numbers of states, discriminates between most models with the same number but a
      different arrangement of states, and extracts meaningful information on the
      relationship between the desensitized states and the phases of macroscopic
      desensitization. When applied to GABA(A) receptor traces (outside out patches,
      alpha 1 beta 2 gamma 2S, 1 mM GABA, >2.5 s), a model with two open states and
      three desensitized states is favored. When applied to simulated data generated
      using a consensus model, CVF leads to reasonable parameter estimates and
      accurately discriminates between this and other models.

PMID- 15240465
TI  - Position 170 of Rabbit Na+/glucose cotransporter (rSGLT1) lies in the Na+
      pathway; modulation of polarity/charge at this site regulates charge transfer and
      carrier turnover.
AB  - Positions 163, 166, and 173, within the putative external loop joining
      transmembrane segments IV and V of rabbit Na(+)/glucose cotransporter, form part
      of its Na(+) interaction and voltage-sensing domain. Since a Q170C mutation
      within this region exhibits anomalous behavior, its function was further
      investigated. We used Xenopus oocytes coinjected with mouse T-antigen to enhance
      Q170C expression, and the two-microelectrode voltage-clamp technique. For Q170C,
      alpha-methyl D-glucopyranoside, phloridzin, and Na(+) affinity values are
      equivalent to those of wild-type; but turnover is reduced approximately 50%.
      Decreased [Na(+)] reduces Q170C, but not wild-type, charge transfer. Q170C
      presteady-state currents exhibit three time constants, tau, identical to wild
      type. MTSES decreases maximal alpha-methyl D-glucopyranoside-induced currents by
      approximately 64% and Na(+) leak by approximately 55%; phloridzin and Na(+)
      affinity are unchanged. MTSES also reduces charge transfer (dithiothreitol
      reversible) and Q170C turnover by approximately 60-70%. MTSEA and MTSET protect
      against MTSES, but neither affect Q170C function. MTSES has no obvious effect on
      the tau-values. Q170A behaves the same as Q170C. The mutation Q170E affects
      voltage sensitivity and reduces turnover, but also appears to influence Na(+)
      interaction. We conclude that 1), glutamine 170 lies in the Na(+) pathway in
      rabbit Na(+)/glucose cotransporter and 2), altered polarity and charge at
      position 170 affect a cotransporter conformational state and transition, which is
      rate-limiting, but probably not associated with empty carrier reorientation.

PMID- 15240466
TI  - AFM visualization of mobile influenza A M2 molecules in planar bilayers.
AB  - We report the observation of influenza A M2 (M2) incorporated in a
      dipalmitoylphosphatidylcholine (DPPC) supported planar bilayer on mica, formed by
      use of a modified vesicle fusion method from proteoliposomes and visualized with
      contact mode atomic force microscopy. Incubation of proteoliposomes in a
      hyperosmotic solution and increased DPPC/M2 weight ratios improved supported
      planar bilayer formation by M2/DPPC proteoliposomes. M2's extra-bilayer domains
      were observed as particles estimated to protrude 1-1.5 nm above the bilayer
      surface and <4 nm in diameter. Particle density was 5-18% of the nominal tetramer
      density. Movement of observable M2 particles was independent of the probe tip.
      The mean lateral diffusion coefficient (D) of M2 was 4.4 +/- 1.0 x 10(-14)
      cm(2)/s. Eighty-two percent of observable particles were mobile on the observable
      timescale (D > 6 x 10(-15) cm(2)/s). Protein-protein interactions were also
      observed directly.

PMID- 15240467
TI  - Properties of a self-assembled phospholipid membrane supported on lipobeads.
AB  - The overall objective of our work was to make a hydrogel-supported phospholipid
      bilayer that models a cytoskeleton-supported cell membrane and provides a
      platform for studying membrane biology. Previously, we demonstrated that a pre
      Lipobead, consisting of phospholipids covalently attached to the surface of a
      hydrogel, could give rise to a Lipobead when incubated with liposomes because the
      attached phospholipids promote self-assembly of a phospholipid membrane on the
      pre-Lipobead. We now report the properties of that Lipobead membrane. The lateral
      diffusion coefficient of fluorescently labeled phosphatidylcholine analogs in the
      membrane was measured by fluorescence recovery after photobleaching and was found
      to decrease as the surface anchor density and hydrogel crosslinking density
      increased. Results from the quenching of phosphatidylcholine analogs suggest that
      the phospholipid membrane of the Lipobead was composed mostly of a semipermeable
      lipid bilayer. However, the diffusional barrier properties of the Lipobead
      membrane were demonstrated by the entrapment of 1.5-3.0 K dextran molecules in
      the hydrogel core after liposome fusion. This hydrogel-supported bilayer membrane
      preparation shows promise as a new platform for studying membrane biology and for
      high throughput drug screening.

PMID- 15240468
TI  - A molecular view on the interaction of the trojan peptide penetratin with the
      polar interface of lipid bilayers.
AB  - Penetratin belongs to the family of Trojan peptides that effectively enter cells
      and therefore can be used as cargoes for agents that are unable to penetrate the
      cell membrane. We applied polarized infrared spectroscopy in combination with the
      attenuated total reflection technique to extract information before penetratin
      binding to lipid membranes with molecular resolution. The amide I band of
      penetratin in the presence of zwitterionic dimyristoylphosphatidylcholine and of
      anionic lipid membranes composed of dioleoylphosphatidylcholine and
      dioleoylphosphatidylglycerol shows the characteristics of an antiparallel beta
      sheet with a small fraction of turns. Both signatures have been interpreted in
      terms of a hairpin conformation. The infrared linear dichroism of the amide I
      band indicates that the peptide chain orients in an oblique fashion whereas the
      plane of the sheet aligns virtually parallel with respect to the membrane
      surface. The weak effect of the peptide on dimyristoylphosphatidylcholine gives
      indication of its superficial binding where the charged lysine and arginine side
      chains form H-bonds to the phosphate oxygens of the surrounding lipids. The
      determinants for internalization of penetratin appear to be a peptide sequence
      with a distribution of positively charged residues along a beta-sheet
      conformation, which enables the anchoring of the peptide in the polar part of the
      membranes and the effective compensation of anionic lipid charges.

PMID- 15240469
TI  - Quantification of Protein-Lipid Selectivity using FRET: Application to the M13
      Major Coat Protein.
AB  - Quantification of lipid selectivity by membrane proteins has been previously
      addressed mainly from electron spin resonance studies. We present here a new
      methodology for quantification of protein-lipid selectivity based on fluorescence
      resonance energy transfer. A mutant of M13 major coat protein was labeled with 7
      diethylamino-3((4'iodoacetyl)amino)phenyl-4-methylcoumarin to be used as the
      donor in energy transfer studies. Phospholipids labeled with N-(7-nitro-2-1,3
      benzoxadiazol-4-yl) were selected as the acceptors. The dependence of protein
      lipid selectivity on both hydrophobic mismatch and headgroup family was
      determined. M13 major coat protein exhibited larger selectivity toward
      phospholipids which allow for a better hydrophobic matching. Increased
      selectivity was also observed for anionic phospholipids and the relative
      association constants agreed with the ones already presented in the literature
      and obtained through electron spin resonance studies. This result led us to
      conclude that fluorescence resonance energy transfer is a promising methodology
      in protein-lipid selectivity studies.

PMID- 15240470
TI  - Kinetics and thermodynamics of association of a phospholipid derivative with
      lipid bilayers in liquid-disordered and liquid-ordered phases.
AB  - We have measured the rates of insertion into, desorption from, and spontaneous
      interlayer translocation (flip-flop) in liquid-disordered and liquid-ordered
      phase lipid bilayer membranes, of the fluorescent phospholipid derivative NBD
      dimyristoylphosphatidyl ethanolamine. This study made use of a recently described
      method that exploits a detailed knowledge of the binding kinetics of an
      amphiphile to bovine serum albumin, to recover the insertion and desorption rate
      constants when the albumin-bound amphiphile is transferred through the aqueous
      phase to the membrane and vice versa. The lipid bilayers, studied as large
      unilamellar vesicles, were prepared from pure 1-palmitoyl-2
      oleoylphosphatidylcholine in the liquid-disordered phase; and from two
      cholesterol-containing binary lipid mixtures, 1-palmitoyl-2
      oleoylphosphatidylcholine and cholesterol (molar ratio of 1:1), and egg
      sphingomyelin and cholesterol (molar ratio of 6:4), both in the liquid-ordered
      phase. Insertion, desorption, and translocation rate constants and equilibrium
      constants for association of the amphiphile monomer with the lipid bilayers were
      directly measured between 15 degrees and 35 degrees C, and the standard free
      energies, enthalpies, and entropies, as well as the activation energies for these
      processes, were derived from this data. The equilibrium partition coefficients
      for partitioning of the amphiphile between the aqueous phase and the different
      membrane phases were also derived, and permitted the estimation of hypothetical
      partition coefficients and the respective energetic parameters for partitioning
      between the different lipid phases if these were to coexist in the same membrane.

PMID- 15240471
TI  - The gaussian curvature elastic modulus of N-monomethylated
      dioleoylphosphatidylethanolamine: relevance to membrane fusion and lipid phase
      behavior.
AB  - The energy of intermediates in fusion of phospholipid bilayers is sensitive to
      kappa(m), the saddle splay (Gaussian curvature) elastic modulus of the lipid
      monolayers. The value kappa(m) is also important in understanding the stability
      of inverted cubic (Q(II)) and rhombohedral (R) phases relative to the lamellar
      (L(alpha)) and inverted hexagonal (H(II)) phases in phospholipids. However,
      kappa(m) cannot be measured directly. It was previously measured by observing
      changes in Q(II) phase lattice dimensions as a function of water content. Here we
      use observations of the phase behavior of N-mono-methylated
      dioleoylphosphatidylethanolamine (DOPE-Me) to determine kappa(m). At the
      temperature of the L(alpha)/Q(II) phase transition, T(Q), the partial energies of
      the two phases are equal, and we can express kappa(m) in terms of known lipid
      monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending
      modulus kappa(m), and the distance of the monolayer neutral surface from the
      bilayer midplane, delta. The calculated ratio kappa(m)/kappa(m) is -0.83 +/- 0.08
      at T(Q) approximately 55 degrees C. The uncertainty is due primarily to
      uncertainty in the value of delta for the L(alpha) phase. This value of
      kappa(m)/kappa(m) is in accord with theoretical expectations, including recent
      estimates of the value required to rationalize observations of rhombohedral (R)
      phase stability in phospholipids. The value kappa(m) substantially affects the
      free energy of formation of fusion intermediates: more energy (tens of k(B)T) is
      required to form stalks and fusion pores (ILAs) than estimated solely on the
      basis of the bending elastic energy. In particular, ILAs are much higher in
      energy than previously estimated. This rationalizes the action of fusion
      catalyzing proteins in stabilizing nascent fusion pores in biomembranes; a
      function inferred from recent experiments in viral systems. These results change
      predictions of earlier work on ILA and Q(II) phase stability and L(alpha)/Q(II)
      phase transition mechanisms. To our knowledge, this is the first determination of
      the saddle splay (Gaussian) modulus in a lipid system consisting only of
      phospholipids.

PMID- 15240472
TI  - NMR study on the binding of neuropeptide achatin-I to phospholipid bilayer: the
      equilibrium, location, and peptide conformation.
AB  - Molecular mechanism of the binding of neuropeptide achatin-I (Gly-D-Phe-Ala-Asp)
      to large unilamellar vesicles of zwitterionic egg-yolk phosphatidylcholine (EPC)
      was investigated by means of natural-abundance (13)C and high-resolution (of 0.01
      Hz order) (1)H NMR spectroscopy. The binding equilibrium was found to be
      sensitive to the ionization state of the N-terminal NH(3)(+) group in achatin-I;
      the de-ionization of NH(3)(+) decreases the bound fraction of the peptide from
      approximately 15% to nearly none. The electrostatic attraction between the N
      terminal positive NH(3)(+) group and the negative PO(4)(-) group in the EPC
      headgroup plays an important role in controlling the equilibrium. Analysis of the
      (13)C chemical shifts (delta) of EPC showed that the binding location of the
      peptide within the bilayer is the polar region between the glycerol and ester
      groups. The binding caused upfield changes Delta delta of the (13)C resonance for
      almost all the carbon sites in achatin-I. The changes Delta delta for the ionic
      Asp at the C-terminus are more than five times as large as those for the other
      residues. The drastic changes for Asp result from the dehydration of the ionic
      CO(2)(-) groups, which are strongly hydrated by electrostatic interactions in
      bulk water. The side-chain conformational equilibria of the aromatic d-Phe and
      ionic Asp residues were both affected by the binding, and the induced changes in
      the equilibria appear to reflect the peptide-lipid hydrophobic interactions.

PMID- 15240473
TI  - Interactions of the human calcitonin fragment 9-32 with phospholipids: a
      monolayer study.
AB  - Human calcitonin and its C-terminal fragment 9-32 (hCT(9-32)) administered in a
      spray translocate into respiratory nasal epithelium with an effect similar to
      intravenous injection. hCT(9-32) is an efficient carrier to transfer the green
      fluorescent protein into excised bovine nasal mucosa. To understand the
      translocation of hCT(9-32) across plasma membranes, we investigated its
      interactions with phospholipids and its interfacial structure using model lipid
      monolayers. A combination of physicochemical methods was applied including
      surface tension measurements on adsorbed and spread monolayers at the air-water
      interface, Fourier transform infrared, circular dichroism, and atomic force
      microscopy on Langmuir-Blodgett monolayers. The results disclose that hCT(9-32)
      preferentially interacts with negatively charged phospholipids and does not
      insert spontaneously into lipid monolayers. This supports a nonreceptor-mediated
      endocytic internalization pathway as previously suggested. Structural studies
      revealed a random coil conformation of hCT(9-32) in solution, transforming to
      alpha-helices when the peptide is localized at lipid-free or lipid-containing air
      water interfaces. Atomic force microscopy studies of monolayers of the peptide
      alone or mixed with dioleoylphosphatidylcholine revealed that hCT(9-32) forms
      filaments rolled into spirals. In contrast, when interacting with
      dioleoylphosphatidylglycerol, hCT(9-32) does not adopt filamentous structures. A
      molecular model and packing is proposed for the spiral-forming hCT(9-32).

PMID- 15240474
TI  - Conformation of peptides in lipid membranes studied by x-ray grazing incidence
      scattering.
AB  - Although the antimicrobial, fungal peptide alamethicin has been extensively
      studied, the conformation of the peptide and the interaction with lipid bilayers
      as well as the mechanism of channel gating are still not completely clear. As
      opposed to studies of the crystalline state, the polypeptide structures in the
      environment of fluid bilayers are difficult to probe. We have investigated the
      conformation of alamethicin in highly aligned stacks of model lipid membranes by
      synchrotron-based x-ray scattering. The (wide-angle) scattering distribution has
      been measured by reciprocal space mappings. A pronounced scattering signal is
      observed in samples of high molar peptide/lipid ratio which is distinctly
      different from the scattering distribution of an ideal helix in the transmembrane
      state. Beyond simple models of ideal helices, the data is analyzed in terms of
      models based on atomic coordinates from the Brookhaven Protein Data Bank, as well
      as from published molecular dynamics simulations. The results can be explained by
      assuming a wide distribution of helix tilt angles with respect to the membrane
      normal and a partial insertion of the N-terminus into the membrane.

PMID- 15240475
TI  - Evolution of a rippled membrane during phospholipase A2 hydrolysis studied by
      time-resolved AFM.
AB  - The sensitivity of phospholipase A(2) (PLA(2)) for lipid membrane curvature is
      explored by monitoring, through time-resolved atomic force microscopy, the
      hydrolysis of supported double bilayers in the ripple phase. The ripple phase
      presents a corrugated morphology. PLA(2) is shown to have higher activity toward
      the ripple phase compared to the gel phase in 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) membranes, indicating its preference for this highly curved
      membrane morphology. Hydrolysis of the stable and metastable ripple structures is
      monitored for equimolar DMPC/1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
      supported double bilayers. As shown by high-performance liquid chromatography
      results, DSPC is resistant to hydrolysis at this temperature, resulting in a more
      gradual hydrolysis of the surface that leads to a change in membrane morphology
      without loss of membrane integrity. This is reflected in an increase in ripple
      spacing, followed by a sudden flattening of the lipid membrane during hydrolysis.
      Hydrolysis of the ripple phase results in anisotropic holes running parallel to
      the ripples, suggesting that the ripple phase has strip regions of higher
      sensitivity to enzymatic attack. Bulk high-performance liquid chromatography
      measurements indicate that PLA(2) preferentially hydrolyzes DMPC in the DMPC/DSPC
      ripples. We suggest that this leads to the formation of a flat gel-phase lipid
      membrane due to enrichment in DSPC. The results point to the ability of PLA(2)
      for inducing a compositional phase transition in multicomponent membranes through
      preferential hydrolysis while preserving membrane integrity.

PMID- 15240476
TI  - A new method for the reconstitution of membrane proteins into giant unilamellar
      vesicles.
AB  - In this work, we have investigated a new and general method for the
      reconstitution of membrane proteins into giant unilamellar vesicles (GUVs). We
      have analyzed systematically the reconstitution of two radically different
      membrane proteins, the sarcoplasmic reticulum Ca(2+)-ATPase and the H(+) pump
      bacteriorhodopsin. In a first step, our method involved a detergent-mediated
      reconstitution of solubilized membrane proteins into proteoliposomes of 0.1-0.2
      microm in size. In a second step, these preformed proteoliposomes were partially
      dried under controlled humidity followed, in a third step, by electroswelling of
      the partially dried film to give GUVs. The physical characteristics of GUVs were
      analyzed in terms of morphology, size, and lamellarity using phase-contrast and
      differential interference contrast microscopy. The reconstitution process was
      further characterized by analyzing protein incorporation and biological activity.
      Both membrane proteins could be homogeneously incorporated into GUVs at
      lipid/protein ratios ranging from 5 to 40 (w/w). After reconstitution, both
      proteins retained their biological activity as demonstrated by H(+) or Ca(2+)
      pumping driven by bacteriorhodopsin or Ca(2+)-ATPase, respectively. This
      constitutes an efficient new method of reconstitution, leading to the production
      of large unilamellar membrane protein-containing vesicles of more than 20 microm
      in diameter, which should prove useful for functional and structural studies
      through the use of optical microscopy, optical tweezers, microelectrodes, or
      atomic force microscopy.

PMID- 15240477
TI  - Structural transients of contractile proteins upon sudden ATP liberation in
      skeletal muscle fibers.
AB  - Structural changes of contractile proteins were examined by millisecond time
      resolved two-dimensional x-ray diffraction recordings during relaxation of
      skinned skeletal muscle fibers from rigor after caged ATP photolysis. It is known
      that the initial dissociation of the rigor actomyosin complex is followed by a
      period of transient active contraction, which is markedly prolonged in the
      presence of ADP by a mechanism yet to be clarified. Both single-headed
      (overstretched muscle fibers with exogenous myosin subfragment-1) and two-headed
      (fibers with full filament overlap) preparations were used. Analyses of various
      actin-based layer line reflections from both specimens showed the following: 1),
      The dissociation of the rigor actomyosin complex was fast and only modestly
      decelerated by ADP and occurred in a single exponential manner without passing
      through any detectable transitory state. Its ADP sensitivity was greater in the
      two-headed preparation but fell short of explaining the large ADP effect on the
      transient active contraction. 2), The decay of the activated state of the thin
      filament followed the time course of tension more closely in an ADP-dependent
      manner. These results suggest that the interplay between the reattached active
      myosin heads and the thin filament is responsible for the prolonged active
      contraction in the presence of ADP.

PMID- 15240478
TI  - Mechanokinetics of rapid tension recovery in muscle: the Myosin working stroke is
      followed by a slower release of phosphate.
AB  - Crystallographic and biochemical evidence suggests that the myosin working stroke
      that generates force in muscle is accompanied by the release of inorganic
      phosphate (Pi), but the order and relative speed of these transitions is not
      firmly established. To address this problem, the theory of A. F. Huxley and R. M.
      Simmons for the length-step response is averaged over elastic strains imposed by
      filament structure and extended to include a Pi-release transition. Models of
      this kind are applied to existing tension-recovery data from length steps at
      different phosphate concentrations, and from phosphate jumps upon release of
      caged phosphate. This body of data is simulated by the model in which the force
      generating event is followed by Pi release. A version in which the Pi-release
      transition is slow provides a better fit than a version with rapid Pi release and
      a slow transition preceding force generation. If Pi is released before force
      generation, the predicted rate of slow recovery increases with the size of the
      step, which is not observed. Some implications for theories of muscle contraction
      are discussed.

PMID- 15240479
TI  - Freely diffusing single hairpin ribozymes provide insights into the role of
      secondary structure and partially folded states in RNA folding.
AB  - Single-molecule fluorescence resonance energy transfer studies of freely
      diffusing hairpin ribozymes with different combinations of helical junction and
      loop elements reveal striking differences in their folding behavior. We examined
      a series of six different ribozymes consisting of two-, three- and four-way
      junction variants, as well as corresponding constructs with one of the two loops
      removed. Our results highlight the varying contributions of preformed secondary
      structure elements to tertiary folding of the hairpin ribozyme. Of the three
      helical junction variants studied, the four-way junction strongly favored folding
      to a docked conformation of the two loops, required for catalytic activity.
      Moreover, the four-way junction was uniquely able to fold to a similar compact
      structure even in the absence of specific loop-loop docking interactions. A key
      feature of the data is the observation of broadening/tailing in the fluorescence
      resonance energy transfer histogram peak for a single-loop mutant of the four-way
      junction at higher Mg(2+) concentrations, not observed for any of the other
      single-loop variants. This feature is consistent with interconversion between
      compact and extended structures, which we estimate takes place on the 100-micros
      timescale using a simple model for the peak shape. This unique ability of the
      four-way junction ribozyme to populate an undocked conformation with native-like
      structure (a quasi-docked state) likely contributes to its greater tertiary
      structure stability, with the quasi-docked state acting as an intermediate and
      facilitating the subsequent formation of the specific hydrogen bonding network
      during docking of the two loops. The inability of two- and three-way junction
      ribozymes to fully populate a docked conformation reveals the importance of
      correct helical junction geometry as well as loop elements for effective ribozyme
      folding.

PMID- 15240480
TI  - The hydrodynamics of DNA electrophoretic stretch and relaxation in a polymer
      solution.
AB  - Theories of DNA electrophoretic separations generally treat the DNA as a free
      draining polymer moving in an electric field at a rate that depends on the
      effective charge density of the molecule. Separations can occur in sieving media
      ranging from ultradilute polymer solutions to tightly cross-linked gels. It has
      recently been shown that DNA is not free-draining when both electric and
      nonelectric forces simultaneously act on the molecule, as occurs when DNA
      collides with a polymer during electrophoretic separations. Here we show that a
      semidilute polymer solution screens the hydrodynamic interaction that results
      from the application of these forces. Fluorescently labeled DNA tethered at one
      end in a semidilute solution of hydroxyl-ethyl cellulose stretch more in an
      electric field than they stretch in free solution, and approach free-draining
      behavior. The steady stretching behavior is predicted without adjustable
      parameters by a theory developed by Stigter using a hydrodynamic screening length
      found from effective medium theory. Data on the relaxation of stretched molecules
      after the electric field is removed agree with the Rouse model prediction, which
      neglects hydrodynamic interactions. The slowest relaxation time constant, tau(R),
      scales with chain length as tau(R) approximately L(1.9+/-0.17) when analyzed by
      the data collapse method, and as tau(R) approximately L(2.17+/-0.17) when
      analyzed by multiexponential fit.

PMID- 15240481
TI  - Crystal structures of two cyanobacterial response regulators in apo- and
      phosphorylated form reveal a novel dimerization motif of phytochrome-associated
      response regulators.
AB  - The structures of two response regulators (RRs) from the cyanobacterium Calothrix
      PCC7601, RcpA and RcpB, were solved to 1.9- and 1.75-A resolution, respectively.
      RcpA was found in phosphorylated and RcpB in nonphosphorylated form. Both RRs are
      members of phytochrome-associated, light-sensing two-component signal
      transduction pathways, based on histidine kinase-mediated receptor
      autophosphorylation and phosphorelay to a RR. Despite the overall folding
      similarity to CheY-type RRs ((beta/alpha)(5)-motif), RcpA and RcpB form
      homodimers, irrespective of their phosphorylation state, giving insight into a
      signal transduction putatively different from that of other known RRs.
      Dimerization is accomplished by a C-terminal extension of the RR polypeptide
      chain, and the surface formed by H4, beta 5, and H5, which constitute a
      hydrophobic contact area with distinct interactions between residues of either
      subunit. Sequence alignments reveal that the identified dimerization motif is
      archetypal for phytochrome-associated RRs, making them a novel subgroup of CheY
      type RRs. The protein structures of RcpA and RcpB are compared to the recently
      presented protein structure of Rcp1 from Synechocystis.

PMID- 15240482
TI  - The long-wavelength chlorophyll states of plant LHCI at room temperature: a
      comparison with PSI-LHCI.
AB  - The red antenna states of the external antenna complexes of higher plant
      photosystem I, known as LHCI, have been analyzed by measurement of their
      preequilibrium fluorescence upon direct excitation at 280 K. In addition to the
      previously detected F735 state, a hitherto undetected low-energy state with
      emission maximum around 713 nm was observed. The 280 K bandwidths (FWHM) are 55
      nm for the F735 state and approximately 27 nm for the F713-nm state, much greater
      than for non-red-shifted antenna chlorophylls. The origin absorption band for the
      F735-nm state was directly detected by determination of its excitation (action)
      spectrum and lies at 709-710 nm. The absorption spectrum for F735, calculated
      using the Stepanov expression, closely overlaps the excitation spectrum,
      indicating that the very large Stokes shift (25 nm) is due to vibrational
      relaxation within the excited-state manifold and solvent effects can be excluded.
      Fluorescence anisotropy measurements, with direct excitation of F735, indicate
      that the transition dipoles of the two red states are parallel. Similar
      experiments performed in the long-wavelength absorbing tail of PSI-LHCI indicate
      the presence of emission state(s) that are red-shifted with respect to F735 of
      isolated LHCI. It is suggested that these are brought about by interactions
      between the complexes in PSI-LHCI, which occur in some yet undefined way, and
      which are broken upon solubilization of the component parts.

PMID- 15240483
TI  - Modeling the backbone dynamics of reduced and oxidized solvated rat microsomal
      cytochrome b5.
AB  - In this article, a description of the statistics and dynamics of cytochrome b(5)
      in both reduced and oxidized forms is given. Results of molecular dynamics
      computer simulations in the explicit solvent have been combined with mode
      coupling diffusion models including and neglecting the molecule-solvent
      correlations. R(1) and R(1 rho) nuclear magnetic relaxation parameters of (15)N
      in the protein backbone have been calculated and compared with experiments.
      Slight changes in charge density in the heme upon oxidation produces a cascade of
      changes in charge distributions from heme propionates up to charged residues
      approximately 1.5 nm from Fe. These changes in charge distributions modify the
      molecular surface and the water shell surrounding the protein. The statistical
      changes upon oxidation can be included in diffusive models that physically
      explain the upper and lower limits of R(1 rho) relaxation parameters at high off
      resonance fields.

PMID- 15240484
TI  - A quantitative XANES analysis of the calcium high-affinity binding site of the
      purple membrane.
AB  - In this article we report x-ray absorption measurements of Ca(2+)-substituted
      bacteriorhodopsin. We present a detailed study of the absorption spectrum close
      to the absorption edge that is very sensitive to the site geometry. We combined
      ab initio calculations of the x-ray absorption cross section based on a full
      multiple scattering approach, with a best fit of the experimental data performed
      by changing the cluster geometry. The Ca(2+)-bacteriorhodopsin environment is
      composed of six oxygen atoms showing a distorted orthorhombic symmetry, whereas
      the Ca(2+) in water solution has a regular octahydrated first sphere of
      coordination. Our results are in good agreement with previous molecular models
      suggesting that the high-affinity cationic site could be in the proximity of the
      retinal pocket. Our results provide strong direct evidence of the specific
      binding site of the metal cation in bacteriorhodopsin.

PMID- 15240485
TI  - Multiple folding pathways of the SH3 domain.
AB  - Experimental observations suggest that proteins follow different folding pathways
      under different environmental conditions. We perform molecular dynamics
      simulations of a model of the c-Crk SH3 domain over a broad range of
      temperatures, and identify distinct pathways in the folding transition. We
      determine the kinetic partition temperature-the temperature for which the c-Crk
      SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-and
      observe that below this temperature the model protein may undergo a folding
      transition by multiple folding pathways via only one or two intermediates. Our
      findings suggest the hypothesis that the SH3 domain, a protein fold for which
      only two-state folding kinetics was observed in previous experiments, may exhibit
      intermediate states under conditions that strongly stabilize the native state.

PMID- 15240486
TI  - Toxin binding of tolevamer, a polyanionic drug that protects against antibiotic
      associated diarrhea.
AB  - Tolevamer, (GT160-246), is a sodium salt of styrene sulfonate polymer that is
      under development for the treatment of diarrhea caused by infection with
      Clostridium difficile. Pulsed ultrafiltration binding experiments in phosphate
      buffer containing 0.15 M Na(+) provide per polymer chain dissociation constants
      of 133 nM and 8.7 microM for the binding of tolevamer to C. difficile toxins A
      and B, respectively. At 0.05 M Na(+), the binding of toxin A to tolevamer is
      irreversible, whereas the dissociation constant to toxin B under these conditions
      is 120 nM. Binding constants obtained from fluorescence polarization data for
      toxin A binding to tolevamer at 0.15 M Na(+) agree substantially with those
      obtained by pulsed ultrafiltration. The binding activity of tolevamer reported
      here correlates well with previously reported results for the inhibition of the
      biological activity of C. difficile toxins A and B. From the fluorescence
      polarization data, it is estimated that one toxin A molecule interacts with
      between 600 to 1000 monomer units on tolevamer at 0.15 M Na(+). Thus, the data
      suggest a very large interaction surface between polymer and toxin A.

PMID- 15240487
TI  - The solution structure and oligomerization behavior of two bacterial toxins:
      pneumolysin and perfringolysin O.
AB  - Pneumolysin (PLY), an important protein virulence factor of the human bacterial
      pathogen Streptococcus pneumoniae, could be a candidate for inclusion in a new
      anti-streptococcal vaccine. PLY solution species from monomer via multimeric
      intermediates to ring-shaped oligomers were studied with time-dependent
      sedimentation velocity in the analytical ultracentrifuge (AUC). Hydrodynamic bead
      modeling was used to interpret the data obtained. PLY remained mostly monomeric
      in solution; intermediate PLY multimers were detected in small quantities.
      Current understanding of PLY molecular mechanism is guided by a model built on
      the basis of its homology with perfringolysin O (PFO) for which there is an
      atomic structure. PFO, a virulence factor of the organism Clostridium
      perfringens, has almost the same molecular mass as PLY and shares 48% sequence
      identity and 60% sequence similarity with PLY. We report a comparative low
      resolution structural study of PLY and PFO using AUC and small-angle x-ray
      scattering (SAXS). AUC data demonstrate that both proteins in solution are mostly
      monodisperse but PLY is a monomer whereas PFO is mostly dimeric. Ab initio dummy
      atom and dummy residue models for PFO and PLY were restored from the distance
      distribution function derived from experimental small-angle x-ray scattering
      curves. In solution, PLY is elongated, consistent with the shape predicted by its
      high-resolution homology model. The PFO dimer is also an elongated particle whose
      shape and volume are consistent with a staggered antiparallel dimer.

PMID- 15240488
TI  - The density and refractive index of adsorbing protein layers.
AB  - The structure of the adsorbing layers of native and denatured proteins
      (fibrinogen, gamma-immunoglobulin, albumin, and lysozyme) was studied on
      hydrophilic TiO(2) and hydrophobic Teflon-AF surfaces using the quartz crystal
      microbalance with dissipation and optical waveguide lightmode spectroscopy
      techniques. The density and the refractive index of the adsorbing protein layers
      could be determined from the complementary information provided by the two in
      situ instruments. The observed density and refractive index changes during the
      protein-adsorption process indicated the presence of conformational changes
      (e.g., partial unfolding) in general, especially upon contact with the
      hydrophobic surface. The structure of the formed layers was found to depend on
      the size of the proteins and on the experimental conditions. On the TiO(2)
      surface smaller proteins formed a denser layer than larger ones and the layer of
      unfolded proteins was less dense than that adsorbed from the native conformation.
      The hydrophobic surface induced denaturation and resulted in the formation of
      thin compact protein films of albumin and lysozyme. A linear correlation was
      found between the quartz crystal microbalance measured dissipation factor and the
      total water content of the layer, suggesting the existence of a dissipative
      process that is related to the solvent molecules present inside the adsorbed
      protein layer. Our measurements indicated that water and solvent molecules not
      only influence the 3D structure of proteins in solution but also play a crucial
      role in their adsorption onto surfaces.

PMID- 15240489
TI  - The unfolding action of GroEL on a protein substrate.
AB  - A molecular dynamics simulation of the active unfolding of denatured rhodanese by
      the chaperone GroEL is presented. The compact denatured protein is bound
      initially to the cis cavity and forms stable contacts with several of the
      subunits. As the cis ring apical domains of GroEL undergo the transition from the
      closed to the more open (ATP-bound) state, they exert a force on rhodanese that
      leads to the increased unfolding of certain loops. The contacts between GroEL and
      rhodanese are analyzed and their variation during the GroEL transition is shown.
      The major contacts, which give rise to the stretching force, are found to be
      similar to those observed in crystal structures of peptides bound to the apical
      domains. The results of the simulation show that multidomain interactions play an
      essential role, in accord with experiments. Implications of the results for
      mutation experiments and for the action of GroEL are discussed.

PMID- 15240490
TI  - pH-dependent dimerization of the carboxyl terminal domain of Cx43.
AB  - Previous studies have demonstrated that the carboxyl terminus of the gap junction
      protein Cx43 (Cx43CT) can act as an independent, regulatory domain that modulates
      intercellular communication in response to appropriate chemical stimuli. Here, we
      have used NMR, chemical cross-linking, and analytical ultracentrifugation to
      further characterize the biochemical and biophysical properties of the Connexin43
      carboxyl terminal domain (S255-I382). NMR-diffusion experiments at pH 5.8
      suggested that the Connexin43 carboxyl terminus (CX43CT) may have a molecular
      weight greater than that of a monomer. Sedimentation equilibrium and cross
      linking data demonstrated a predominantly dimeric state for the Cx43CT at pH 5.8
      and 6.5, with limited dimer formation at a more neutral pH. NMR-filtered nuclear
      Overhauser effect studies confirmed these observations and identified specific
      areas of parallel orientation within Cx43CT, likely corresponding to dimerization
      domains. These regions included a portion of the SH3 binding domain, as well as
      two fragments previously found to organize in alpha-helical structures. Together,
      these data show that acidification causes Cx43CT dimer formation in vitro.
      Whether dimer formation is an important structural component of the regulation of
      Connexin43 channels remains to be determined. Dimerization may alter the affinity
      of Cx43CT regions for specific molecular partners, thus modifying the regulation
      of gap junction channels.

PMID- 15240491
TI  - A new method of identifying the site of tyrosyl radicals in proteins.
AB  - Protein-bound tyrosyl radicals catalyze many important enzymatic reactions. They
      can also initiate oxidative damage to cells. Here we report a new method of
      computer simulation of tyrosyl radical electron paramagnetic resonance spectra.
      The method enables the determination of the rotational conformation of the
      phenoxyl ring in a radical with unprecedented accuracy (approximately 2 degrees
      ). When coupled with a new online database, all tyrosine residues in a protein
      can be screened for that particular conformation. For the first time we show
      relationships between the spin density on atom C1 (rho(C1)) and the principal g
      factors measured by electron paramagnetic resonance spectroscopy (rho(C1) on g(x)
      is shown to be linear). The new method enables the accurate determination of
      rho(C1) in all known tyrosyl radicals, evaluates the likelihood of a hydrogen
      bond, and determines the possibility of a rho(C1) distribution in the radicals.
      This information, together with the accurately determined rotational
      conformation, is frequently sufficient to allow for an unambiguous identification
      of the site of radical formation. The possibility of a similar relationship
      between rho(C) and g(x) in other radicals, e.g., tryptophanyl, is discussed.

PMID- 15240492
TI  - Folding lambda-repressor at its speed limit.
AB  - We show that the five-helix bundle lambda(6-85) can be engineered and solvent
      tuned to make the transition from activated two-state folding to downhill
      folding. The transition manifests itself as the appearance of additional dynamics
      faster than the activated kinetics, followed by the disappearance of the
      activated kinetics when the bias toward the native state is increased. Our
      fastest value of 1 micros for the "speed" limit of lambda(6-85) is measured at
      low concentrations of a denaturant that smooths the free-energy surface. Complete
      disappearance of the activated phase is obtained in stabilizing glucose buffer.
      Langevin dynamics on a rough free-energy surface with variable bias toward the
      native state provides a robust and quantitative description of the transition
      from activated to downhill folding. Based on our simulation, we estimate the
      residual energetic frustration of lambda(6-85) to be delta(2) G approximately
      0.64 k(2)T(2). We show that lambda(6-86), as well as very fast folding proteins
      or folding intermediates estimated to lie near the speed limit, provide a better
      rate-topology correlation than proteins with larger energetic frustration. A
      limit of beta > or = 0.7 on any stretching of lambda(6-85) barrier-free dynamics
      suggests that a low-dimensional free-energy surface is sufficient to describe
      folding.

PMID- 15240493
TI  - Nanostructure of cationic lipid-oligonucleotide complexes.
AB  - Complexes (lipoplexes) between cationic liposomes and single-strand
      oligodeoxynucleotides (ODN) are potential delivery systems for antisense therapy.
      The nanometer-scale morphology of these assemblies is relevant to their
      transfection efficiency. In this work the monocationic lipid
      dioleoyloxytrimethylammoniumpropane, the neutral "helper" lipid cholesterol, and
      an 18-mer anti-bcl2 ODN were combined at different ratios. The lipoplexes formed
      were characterized for the quantity of ODN bound, for the degree of lipid mixing,
      and for their size. The nanostructure of the system was examined by cryogenic
      temperature transmission electron microscopy, augmented by small-angle x-ray
      scattering. Addition of ODN to cationic liposomes induced both liposome
      aggregation and the formation of a novel condensed lamellar phase. This phase is
      proposed to be stabilized by anionic single-strand ODN molecules intercalated
      between cationic bilayers. The proportion of cholesterol present apparently did
      not affect the nature of lipoplex microstructure, but changed the interlamellar
      spacing.

PMID- 15240494
TI  - A nanosensor for transmembrane capture and identification of single nucleic Acid
      molecules.
AB  - We have engineered a nanosensor for sequence-specific detection of single nucleic
      acid molecules across a lipid bilayer. The sensor is composed of a protein
      channel nanopore (alpha-hemolysin) housing a DNA probe with an avidin anchor at
      the 5' end and a nucleotide sequence designed to noncovalently bind a specific
      single-stranded oligonucleotide at the 3' end. The 3' end of the DNA probe is
      driven to the opposite side of the pore by an applied electric potential, where
      it can specifically bind to oligonucleotides. Reversal of the applied potential
      withdraws the probe from the pore, dissociating it from a bound oligonucleotide.
      The time required for dissociation of the probe-oligonucleotide duplex under this
      force yields identifying characteristics of the oligonucleotide. We demonstrate
      transmembrane detection of individual oligonucleotides, discriminate between
      molecules differing by a single nucleotide, and investigate the relationship
      between dissociation time and hybridization energy of the probe and analyte
      molecules. The detection method presented in this article is a candidate for in
      vivo single-molecule detection and, through parallelization in a synthetic
      device, for genotyping and global transcription profiling from small samples.

PMID- 15240496
TI  - High sensitivity of Stark-shift voltage-sensing dyes by one- or two-photon
      excitation near the red spectral edge.
AB  - Sensitivity spectra of Stark-shift voltage sensitive dyes, such as ANNINE-6,
      suggest the use of the extreme red edges of the excitation spectrum to achieve
      large fractional fluorescence changes with membrane voltage. This was tested in
      cultured HEK293 cells. Cells were illuminated with light at the very red edge of
      the dye's excitation spectrum, where the absorption cross section is as much as
      100 times smaller than at its peak. The small-signal fractional fluorescence
      changes were -0.17%/mV, -0.28%/mV, and -0.35%/mV for one-photon excitation at 458
      nm, 488 nm, and 514 nm, respectively, and -0.29%/mV, -0.43%/mV, and -0.52%/mV for
      two-photon excitation at 960 nm, 1000 nm, and 1040 nm, respectively. For large
      voltage swings the fluorescence changes became nonlinear, reaching 50% and -28%
      for 100 mV hyper- and depolarization, respectively, at 514 nm and 70% and -40% at
      1040 nm. Such fractional sensitivities are approximately 5 times larger than what
      is commonly found with other voltage-sensing dyes and approach the theoretical
      limit given by the spectral Boltzmann tail.

PMID- 15240495
TI  - Structure of A beta(25-35) peptide in different environments.
AB  - The fragment A beta(25-35) of the Alzheimer's amyloid beta-peptide, like its full
      length peptide A beta(1-42), has shown neurotoxic activities in cultured cells.
      The conformational preference of this important peptide is examined here in
      solution, gel, and film states (obtained with organic and aqueous solvents) by
      vibrational circular dichroism spectroscopy for the first time. For comparative
      studies, vibrational absorption and electronic circular dichroism measurements
      were also carried out under identical conditions. The peptide was found to adopt
      beta-sheet and beta-turn structures, with their relative proportions changing in
      different environments.

PMID- 15240497
TI  - New aspects of the alpha-helix to beta-sheet transition in stretched hard alpha
      keratin fibers.
AB  - The putative transformation of alpha-helices into beta-sheets has been studied
      for more than 50 years in the case of hard alpha-keratin. In a previous study of
      stretched keratin fibers, we specified the conditions for beta-sheet appearance
      within horsehair: the formation of beta-sheets requires at least 30% relative
      humidity. However, this phenomenon was observed in the whole tissue. Then there
      was no clear chemical identification of the beta-sheets (keratin or matrix
      proteins) and the exact location of the beta-sheets across the fiber could not be
      specified. In this study, using wide-angle x-ray scattering and high spatial
      resolution infrared microspectroscopy, we could determine and characterize the
      structural elements across hair sections stretched in water, which provides new
      information about the aforementioned transition. Our results show that the
      process can be split into three steps: 1), unraveling of the alpha-helical coiled
      coil domains, which starts at roughly 5% macroscopic strain; 2), further
      transformation of the unraveled coiled-coils into beta-sheet structures, which
      occurs above roughly 20% macroscopic strain; and 3), spatial expanding of the
      beta-structured zones from the sample center to its periphery.

PMID- 15240498
TI  - Novel spectroscopic technique for in situ monitoring of collagen fibril alignment
      in gels.
AB  - Development of collagen fibril alignment in contracting fibroblast-populated and
      externally tensioned acellular collagen gels was studied using elastic scattering
      spectroscopy. Spectra of the backscattered light (320-860 nm) were acquired with
      a 2.75-mm source-detector separation probe placed perpendicular to the gel
      surface and rotated to achieve different angles to the collagen fibril alignment.
      Backscatter was isotropic for noncontracted/unloaded gels (disorganized matrix).
      As gels were contracted/externally loaded (collagen alignment developed),
      anisotropy of backscatter increased: more backscatter was detected perpendicular
      than parallel to the direction of the fibril alignment. An "anisotropy factor"
      (AF) was calculated to characterize this effect as the ratio of backscatter
      intensities at orthogonal positions. Before contraction (or zero strain) the AF
      was close to unity at all wavelengths. In contrast, at 72 h, backscatter
      anisotropy varied from AF(400 nm) = 2.14 +/- 0.29 to AF(700 nm) = 3.04 +/- 0.48.
      It also increased over threefold up to a strain of 20%. The AF strongly
      correlated with the contraction time/strain. Different directions of the
      backscatter were detected in gel zones with known differences in the matrix
      alignment. Thus, backscatter anisotropy allows in situ nondestructive
      determination of collagen fibril alignment and quantitative monitoring of its
      development.

PMID- 15240499
TI  - Placing single-molecule T4 lysozyme enzymes on a bacterial cell surface: toward
      probing single-molecule enzymatic reaction in living cells.
AB  - The T4 lysozyme enzymatic hydrolyzation reaction of bacterial cell walls is an
      important biological process, and single-molecule enzymatic reaction dynamics
      have been studied under physiological condition using purified Escherichia coli
      cell walls as substrates. Here, we report progress toward characterizing the T4
      lysozyme enzymatic reaction on a living bacterial cell wall using a combined
      single-molecule placement and spectroscopy. Placing a dye-labeled single T4
      lysozyme molecule on a targeted bacterial cell wall by using a hydrodynamic
      microinjection approach, we monitored single-molecule rotational motions during
      binding, attachment to, and dissociation from the cell wall by tracing single
      molecule fluorescence intensity time trajectories and polarization. The single
      molecule attachment duration of the T4 lysozyme to the cell wall during enzymatic
      reactions was typically shorter than the photobleaching time under physiological
      conditions. Applying single-molecule fluorescence polarization measurements to
      characterize the binding and motions of the T4 lysozyme molecules, we observed
      that the motions of wild-type and mutant T4 lysozyme proteins are essentially the
      same whether under an enzymatic reaction or not. The changing of the fluorescence
      polarization suggests that the motions of the T4 lysozyme are associated with
      orientational rotations. This observation also suggests that the T4 lysozyme
      binding-unbinding motions on cell walls involve a complex mechanism beyond a
      single-step first-order rate process.

PMID- 15240500
TI  - Secondary structure and lipid contact of a peptide antibiotic in phospholipid
      bilayers by REDOR.
AB  - The chemical shifts of specific (13)C and (15)N labels distributed throughout
      KIAGKIA-KIAGKIA-KIAGKIA (K3), an amphiphilic 21-residue antimicrobial peptide,
      prove that the peptide is in an all alpha-helical conformation in the bilayers of
      multilamellar vesicles (MLVs) containing dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylglycerol (1:1). Rotational-echo double-resonance (REDOR)
      (13)C[(31)P] and (15)N[(31)P] experiments on the same labeled MLVs show that on
      partitioning into the bilayer, the peptide chains remain in contact with lipid
      headgroups. The amphipathic lysine side chains of K3 in particular appear to play
      a key role in the electrostatic interactions with the acidic lipid headgroups. In
      addition to the extensive peptide-headgroup contact, (13)C[(19)F] REDOR
      experiments on MLVs containing specifically (19)F-labeled lipid tails suggest
      that a portion of the peptide is surrounded by a large number of lipid acyl
      chains. Complementary (31)P[(19)F] REDOR experiments on these MLVs show an
      enhanced headgroup-lipid tail contact resulting from the presence of K3. Despite
      these distortions, static (31)P NMR lineshapes indicate that the lamellar
      structure of the membrane is preserved.

PMID- 15240501
TI  - Structure of (KIAGKIA)3 aggregates in phospholipid bilayers by solid-state NMR.
AB  - The interchain (13)C-(19)F dipolar coupling measured in a rotational-echo double
      resonance (REDOR) experiment performed on mixtures of differently labeled KIAGKIA
      KIAGKIA-KIAGKIA (K3) peptides (one specifically (13)C labeled, and the other
      specifically (19)F labeled) in multilamellar vesicles of
      dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol (1:1) shows
      that K3 forms close-packed clusters, primarily dimers, in bilayers at a
      lipid/peptide molar ratio (L/P) of 20. Dipolar coupling to additional peptides is
      weaker than that within the dimers, consistent with aggregates of monomers and
      dimers. Analysis of the sideband dephasing rates indicates a preferred
      orientation between the peptide chains of the dimers. The combination of the
      distance and orientation information from REDOR is consistent with a parallel (N
      N) dimer structure in which two K3 helices intersect at a cross-angle of
      approximately 20 degrees. Static (19)F NMR experiments performed on K3 in
      oriented lipid bilayers show that between L/P = 200 and L/P = 20, K3 chains
      change their absolute orientation with respect to the membrane normal. This
      result suggests that the K3 dimers detected by REDOR at L/P = 20 are not on the
      surface of the bilayer but are in a membrane pore.

PMID- 15240502
TI  - Controlled pseudopod extension of human neutrophils stimulated with different
      chemoattractants.
AB  - The formation of pseudopods and lamellae after ligation of chemoattractant
      sensitive G-protein coupled receptors (GPCRs) is essential for chemotaxis. Here,
      pseudopod extension was stimulated with chemoattractant delivered from a
      micropipet. The chemoattractant diffusion and convection mass transport were
      considered, and it is shown that when the delivery of chemoattractant was limited
      by diffusion there was a strong chemoattractant gradient along the cell surface.
      The diffusion-limited delivery of chemoattractant from a micropipet allowed for
      maintaining an almost constant chemoattractant concentration at the leading edge
      of single pseudopods during their growth. In these conditions, the rate of
      pseudopod extension was dependent on the concentration of chemoattractant in the
      pipet delivering chemoattractant. The pseudopod extension induced using
      micropipets was oscillatory even in the presence of a constant delivery of
      chemoattractant. This oscillatory pseudopod extension was controlled by activated
      RhoA and its downstream effector kinase ROCK and was abolished after the
      inhibition of RhoA activation with Clostridium botulinium C3 exoenzyme (C3) or
      the blocking of ROCK activation with Y-27632. The ability of the micropipet assay
      to establish a well-defined chemoattractant distribution around the activated
      cell over a wide range of molecular weights of the used chemoattractants allowed
      for comparison of the effect of chemoattractant stimulation on the dynamics of
      pseudopod growth. Pseudopod growth was stimulated using N-formylated peptide (N
      formyl-methionyl-leucyl-phenylalanine (fMLP)), platelet activating factor (PAF),
      leukotriene B4 (LTB(4)), C5a anaphylotoxin (C5a), and interleukin-8 (IL-8), which
      represent the typical ligands for G-protein coupled chemotactic receptors. The
      dependence of the rate of pseudopod extension on the concentration of these
      chemoattractants and their equimolar mixture was measured and shown to be similar
      for all chemoattractants. The inhibition of the activity of phosphoinositide-3
      kinase (PI3K) with wortmannin showed that 72%-80% of the rate of pseudopod
      extension induced with N-formyl-methionyl-leucyl-phenylalanine, platelet
      activating factor, and leukotriene B4 was phosphoinositide-3 kinase-dependent, in
      contrast to 55% of the rate of pseudopod extension induced with interleukin-8.
      The dependence of the rate of pseudopod extension on the concentration of
      individual chemoattractants and their equimolar mixture suggests that there is a
      common rate-limiting mechanism for the polymerization of cytoskeletal F-actin in
      the pseudopod region induced by G-protein coupled chemoattractant receptors.

PMID- 15240503
TI  - Analysis of functional coupling: mitochondrial creatine kinase and adenine
      nucleotide translocase.
AB  - The mechanism of functional coupling between mitochondrial creatine kinase (MiCK)
      and adenine nucleotide translocase (ANT) in isolated heart mitochondria is
      analyzed. Two alternative mechanisms are studied: 1), dynamic compartmentation of
      ATP and ADP, which assumes the differences in concentrations of the substrates
      between intermembrane space and surrounding solution due to some diffusion
      restriction and 2), direct transfer of the substrates between MiCK and ANT. The
      mathematical models based on these possible mechanisms were composed and
      simulation results were compared with the available experimental data. The first
      model, based on a dynamic compartmentation mechanism, was not sufficient to
      reproduce the measured values of apparent dissociation constants of MiCK reaction
      coupled to oxidative phosphorylation. The second model, which assumes the direct
      transfer of substrates between MiCK and ANT, is shown to be in good agreement
      with experiments--i.e., the second model reproduced the measured constants and
      the estimated ADP flux, entering mitochondria after the MiCK reaction. This model
      is thermodynamically consistent, utilizing the free energy profiles of reactions.
      The analysis revealed the minimal changes in the free energy profile of the MiCK
      ANT interaction required to reproduce the experimental data. A possible free
      energy profile of the coupled MiCK-ANT system is presented.

PMID- 15240504
TI  - Determination of cell capacitance using the exact empirical solution of partial
      differential Y/partial differential Cm and its phase angle.
AB  - Measures of membrane capacitance offer insight into a variety of cellular
      processes. Unfortunately, popular methodologies rely on model simplifications
      that sensitize them to interference from inevitable changes in resistive
      components of the traditional cell-clamp model. Here I report on a novel method
      to measure membrane capacitance that disposes of the usual simplifications and
      assumptions, yet is immune to such interference and works on the millisecond
      timescale. It is based on the exact empirical determination of the elusive
      partial derivative, partial differential Y/partial differential C(m), which
      heretofore had been approximated. Furthermore, I illustrate how this method
      extends to the vesicle fusion problem by permitting the determination of partial
      differential Y(v)/partial differential C(v), thereby providing estimates of
      fusion pore conductance and vesicle capacitance. Finally, I provide simulation
      examples and physiological examples of how the method can be used to study
      processes that are routinely interrogated by measures of membrane capacitance.

PMID- 15240505
TI  - Prion kinetics.

PMID- 15240507
TI  - Histone H4 histidine kinase displays the expression pattern of a liver
      oncodevelopmental marker.
AB  - Protein phosphorylation is a vital process in the regulation of mammalian cell
      division and the protein kinases that catalyze the phosphorylation of proteins on
      serine, threonine and tyrosine residues have been well characterized. In
      contrast, little is known about the kinases involved in protein histidine
      phosphorylation, which have been described in various mammalian cells that are
      highly proliferative. Histone H4 histidine kinase (HHK) activity is highly active
      in regenerating rat liver. Using a novel and specific assay, we demonstrate that
      it is active in human fetal liver, essentially absent in adult liver and highly
      expressed in liver tumours. 'Normal' liver surrounding the HCC contains low to
      undetectable levels of HHK. In a rodent model of chronic liver injury that leads
      to HCC, its activity is induced. Two lines of evidence suggest that liver
      progenitor (oval) cells, which populate the liver at early stages following
      induction of liver damage are responsible for the increased activity. Purified
      oval cells, as well as cell lines established from primary cultures of oval cells
      express high levels of HHK. We propose that the pattern of expression of histone
      H4 histidine kinase activity justifies its classification as an oncodevelopmental
      marker and suggest it may be useful as a diagnostic marker for hepatocellular
      carcinoma as well for identifying preneoplastic lesions.

PMID- 15240508
TI  - Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats
      initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, with induction of cytochrome
      P450s in the liver and consequent modulation of estrogen metabolism.
AB  - Indole-3-carbinol (I3C), found in cruciferous vegetables, has been shown to
      suppress or promote carcinogenesis depending on various animal models. Regarding
      its preventive effects, I3C acts as an anti-estrogen and can induce apoptosis,
      but precise mechanisms remain to be determined. Since I3C induces cytochrome P450
      enzymes in the liver, it affects hydroxylation of estrogens and might therefore
      be expected to influence endometrial adenocarcinoma development. The present
      study was performed to clarify the effects of I3C using a rat two-stage
      endometrial carcinogenesis model, focusing on induction of cytochrome P450s and
      other estrogen-metabolic enzymes in the liver. First, to determine the estrogenic
      or anti-estrogenic activity, an uterotropic assay was conducted using
      ovariectomized Donryu rats (experiment 1). Second, to elucidate the effects on
      endometrial carcinogenicity, female Donryu rats initiated with a single dose of N
      ethyl-N'-nitro-N-nitrosoguanidine into a uterine horn were fed 0 or 500 p.p.m.
      I3C in diets for 12 months (experiment 2). In experiment 3, similarly initiated
      animals received 0 or 2000 p.p.m. I3C in their diet, or 1 microg/kg 17beta
      estradiol (E2) or 5 microg/kg 4-hydroxyestradiol (4HE) subcutaneously twice a
      week for 12 months. In the uterotrophic assay, neither 500 nor 2000 p.p.m. of I3C
      showed any estrogenic or anti-estrogenic activity. In the two uterine
      carcinogenicity studies, I3C and 4HE increased incidences of uterine
      adenocarcinomas and/or multiplicities of uterine proliferative lesions, E2
      treatment being associated with a tendency for promotion. In the liver, I3C
      treatment consistently elevated estradiol 2- and 4-hydroxylase activities, in
      particular the latter, but without effects on estradiol 16alpha-hydoxylase
      activity. mRNAs for CYP 1A1, 1A2 and 1B1 were increased by I3C treatment, with
      translation confirmed immunohistochemically. These results suggest that induction
      of the CYP 1 family in the liver and sequential modulation of estrogen metabolism
      to increase 4HE might play a crucial role in promoting the effects of dietary I3C
      on endometrial adenocarcinoma development.

PMID- 15240509
TI  - Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic
      bronchial lesions.
AB  - AKT is frequently activated in various cancers, but its involvement in lung tumor
      development and progression is not well established. We examined AKT activity by
      immunohistochemistry in 110 non-small cell lung carcinomas (NSCLCs) using tissue
      microarrays. AKT activation was observed in 56 (51%) tumors. To further validate
      activation of the AKT pathway in this series, we examined the phosphorylation
      status of the mammalian target of rapamycin (mTOR) and forkhead (FKHR), two
      downstream targets of AKT. Positive staining for phospho-mTOR and phospho-FKHR
      were detected in 74% and 68% of tumors, respectively, and was significantly
      associated with activation of AKT. Tumors positive for phosphorylated (active)
      AKT were present with a similar frequency in low stage (I/II) and high stage
      (III/IV) tumors, raising the possibility that AKT activation occurs early in
      tumor progression. We therefore examined AKT activity in 25 bronchial epithelial
      lesions from 12 patients at high risk of lung cancer. Metaplastic/dysplastic
      areas showed AKT activity, whereas normal and hyperplastic bronchial epithelia
      exhibited little or no activity. Since some bronchial epithelial lesions may
      develop into invasive cancers, we examined the effect of AKT on invasiveness of
      lung cancer cells, using an in vitro cell invasion assay. Transfection of NSCLC
      cells with wild-type AKT increased invasiveness in response to hepatocyte growth
      factor, whereas transfection with dominant negative AKT abrogated this effect.
      Collectively, these data suggest that AKT activation is a frequent and early
      event in lung tumorigenesis, which may enhance risk of progression to malignancy.
      Thus, AKT represents a potentially important target for chemoprevention in
      individuals at high risk of NSCLC.

PMID- 15240510
TI  - Hepatocyte growth factor-activated NF-kappaB regulates HIF-1 activity and ODC
      expression, implicated in survival, differently in different carcinoma cell
      lines.
AB  - Hepatocyte growth factor (HGF)-stimulated Met signaling influences tumor
      survival, growth and progression, all processes involving the transcription
      factor NF-kappaB. NF-kappaB plays a complex role in the control of survival due
      to the influence of cellular factors acting downstream. We undertook a
      comparative investigation of two human breast carcinoma cells with different
      grades of malignancy and HepG2 hepatoma cells, which present a biphasic response
      to HGF (proliferation followed by apoptosis). We found evidence that HGF induced
      gene patterns characteristic of survival rather than apoptosis depending on the
      cell type. The ability of NF-kappaB to regulate expression of hypoxia-inducible
      factor-1alpha (HIF-1alpha), a survival/anti-apoptotic gene in cancer, seemed to
      be critical. In the HepG2 and MCF-7 (low invasive breast carcinoma) cell lines
      increased transcription and translation were responsible for HIF-1alpha induction
      after HGF. The regulation by NF-kappaB was mainly at the level of the 5'-UTR of
      the HIF-1alpha message. HIF-1 (alpha/beta heterodimer) was likely to
      transactivate Mcl-1, another anti-apoptotic gene. Opposite results were observed
      in MDA-MB-231 cells (highly invasive breast carcinoma), which have high NF-kappaB
      activity, further inducible by HGF, because HIF-1alpha mRNA expression and HIF-1
      transactivating capacity were HGF-insensitive while the alpha subunit seemed to
      be degraded after HGF. However, ornithine decarboxylase (ODC) and heme oxygenase
      mRNA expression persistently increased. By transiently transfecting two ODC gene
      reporters we demonstrated that ODC is a target gene of NF-kappaB in HGF-treated
      tumor cells. By regulating HIF-1 activity and specific gene expression
      downstream, NF-kappaB may influence the survival threshold, with an impact on the
      fate of carcinoma cells after prolonged HGF treatment.

PMID- 15240511
TI  - BC200 RNA in invasive and preinvasive breast cancer.
AB  - BC200 RNA, a small functional RNA that operates as a translational modulator, has
      been implicated in the regulation of local synaptodendritic protein synthesis in
      neurons. Cell type-specific expression of BC200 RNA is tightly controlled such
      that the RNA is not normally detected in somatic cells other than neurons.
      However, the neuron-specific control of BC200 expression is deregulated in a
      number of tumors. We here report that BC200 RNA is expressed at high levels in
      invasive carcinomas of the breast. In normal breast tissue or in benign tumors
      such as fibroadenomas, in contrast, we found that the RNA is not detectable at
      significant levels. The difference in expression levels between invasive
      carcinomas and normal/benign tissue was statistically highly significant.
      Receiver Operating Characteristics analysis of sensitivity and specificity
      confirmed the diagnostic power of BC200 RNA as a molecular marker of invasive
      breast cancer. In ductal carcinomas in situ, furthermore, significant BC200
      expression was associated with high nuclear grade, suggesting that the presence
      of BC200 RNA in such tumors may be used as a prognostic indicator of tumor
      progression. The combined results demonstrate the potential of BC200 expression
      to serve as a molecular tool in the diagnosis and/or prognosis of breast cancer.

PMID- 15240512
TI  - p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and
      the precancerous lesions.
AB  - The development of intestinal gastric carcinoma involves several precancerous
      stages. The environmental factor plays an important role in gastric
      carcinogenesis, while the host's genetic makeup may influence the susceptibility
      to cancer. In this study we investigated correlations of the p53 variations at
      codon 72 and p21(WAF1/CIP1) haplotype with the risk of intestinal gastric
      carcinoma. Forty-eight intestinal gastric carcinoma cases (GC), 96 chronic
      atrophic gastritis (CAG), 96 intestinal metaplasia (IM) and 96 dysplasia (DYS)
      controls were enrolled in this study. The p53 codon 72 proline allele carriers
      were found to be more susceptible to progress to GC than to IM (OR = 2.22, 95%CI
      = 1.05-4.70, P = 0.038). Patients carrying homozygous p21(WAF1/CIP1) haplotype A,
      which contains the serine at codon 31, the cytidine at the 16th base of the
      second intron, and the cytidine at the 70th base of the exon 3 were more prone to
      develop GC than to reach the IM or DYS stage (IM versus GC, OR = 3.35, 95%CI =
      1.11-10.15; DYS versus GC, OR = 3.27, 95%CI = 1.09-9.80, P = 0.035). The
      combination of p53 codon 72 variation with the p21(WAF1/CIP1) haplotype further
      distinguished the risk of GC from IM precancerous lesion (OR = 9.31, 95% CI =
      1.77-48.85, P = 0.08). These results suggest that p53 and/or p21(WAF1/CIP1)
      genotype may influence the progression during gastric tumorigenesis.

PMID- 15240513
TI  - Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer.
AB  - PURPOSE: The purpose of this research was to evaluate toxicity, response, and
      changes in oxygenation (pO(2)) in patients with locally advanced breast cancer
      (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy
      (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC
      were enrolled from October 1995 through February 1999. Treatment consisted of
      taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy
      included the breast and regional nodes with a dose of 50 Gy, followed by a boost
      to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for
      patients deemed resectable after this neoadjuvant program. HT was administered
      twice per week. Oxygenation was measured before the first HT treatment and 24 h
      after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a
      clinical complete response, 9 with a partial clinical response, and 3
      nonresponders. Thirteen underwent mastectomy with 3 pathological complete
      responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2
      mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg).
      Patients with well-oxygenated tumors before treatment as well as those with
      significant reoxygenation had a favorable clinical response. Tumor reoxygenation
      appeared to be temperature dependent and associated with the lower thermal doses.
      CONCLUSIONS: This novel therapeutic program resulted in a high response rate in
      patients with LABC. Hyperthermia may offer a strategy for improving tumor
      reoxygenation with consequent treatment response. However, the effect of
      hyperthermia on tumor reoxygenation appears to depend on thermal dose and
      requires additional investigation.

PMID- 15240514
TI  - The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can
      be selectively down-regulated in the thyroid.
AB  - PURPOSE: The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that
      mediates active iodide (I(-)) transport in the thyroid, lactating breast, and
      other tissues. Functional NIS expression in thyroid cancer accounts for the
      longstanding success of radioactive iodide ((131)I) ablation of metastases after
      thyroidectomy. Breast cancer is the only other cancer demonstrating endogenous
      functional NIS expression. Until now, NIS activity in breast cancer metastases
      (BCM) was unproven. EXPERIMENTAL DESIGN: Twenty-seven women were scanned with
      (99m)TcO(4)(-) or (123)I(-) to assess NIS activity in their metastases. An (131)I
      dosimetry study was offered to patients with I(-)-accumulating tumors. Selective
      down-regulation of thyroid NIS was tested in 13 patients with T(3) and in one
      case with T(3) + methimazole (MMI; blocks I(-) organification). NIS expression
      was evaluated in index and/or metastatic tumor samples by immunohistochemistry.
      RESULTS: I(-) uptake was noted in 25% of NIS-expressing tumors (two of eight).
      The remaining cases did not show NIS expression or activity. Thyroid I(-) uptakes
      were decreased to </=2.8% at 24 h in T(3)-treated patients and 1/100 normal with
      T(3)/MMI. Uptake (2.9%) was calculated in a peribronchial metastasis on (131)I
      dosimetry scans at 4 h with disappearance of the signal by 24 h. We estimated a
      therapeutic dose of 3000 cGy could be achieved in this metastasis with 100 mCi of
      (131)I if the tumor exhibited the same dynamics as the T(3)/MMI-suppressed
      thyroid. CONCLUSIONS: This is the first article of in vivo, scintigraphically
      detected, NIS-mediated I(-) accumulation in human BCM. T(3)/MMI down-regulation
      of thyroid NIS makes (131)I-radioablation of BCM possible with negligible thyroid
      uptake and radiation damage.

PMID- 15240515
TI  - Imaging correlates of molecular signatures in oligodendrogliomas.
AB  - Molecular subsets of oligodendroglioma behave in biologically distinct ways.
      Their locations in the brain, rates of growth, and responses to therapy differ
      with their genotypes. Retrospectively, we inquired whether allelic loss of
      chromosomal arms 1p and 19q, an early molecular event and favorable prognostic
      marker in oligodendrogliomas, were reflected in their appearance on magnetic
      resonance imaging. Loss of 1p and 19q was associated with an indistinct border on
      T(1) images and mixed intensity signal on T(1) and T(2). Loss of 1p and 19q was
      also associated with paramagnetic susceptibility effect and with calcification, a
      common histopathological finding in oligodendrogliomas. These data encourage
      prospective evaluation of molecular alterations and magnetic resonance imaging
      characteristics of glial neoplasms.

PMID- 15240516
TI  - The tumor-associated antigen PRAME is universally expressed in high-stage
      neuroblastoma and associated with poor outcome.
AB  - PURPOSE: The tumor-associated antigen PRAME, a potential candidate for
      immunotherapeutic targeting, is frequently expressed in a variety of cancers.
      However, no information about its presence in neuroblastoma is available to date.
      We therefore evaluated and quantified PRAME expression in a considerable number
      of neuroblastoma tumors and assessed its impact on the outcome of patients.
      EXPERIMENTAL DESIGN: Qualitative analysis of PRAME expression was assessed by
      reverse transcription (RT)-PCR screening of 94 patients with primary
      neuroblastoma. The same cohort was used for semiquantitative determination of
      transcript levels by Northern blotting, comparing the signal intensities of
      patients with those of testis total RNA. For more precise quantification of PRAME
      expression, real-time RT-PCR was performed in 88 patients of the above cohort and
      7 additional patients, thus leaving a total of 101 patients that were analyzed
      with either method. Furthermore, association with tumor stage, age of patients at
      diagnosis, and MYCN amplification was determined as well as the prognostic impact
      of PRAME expression. RESULTS: RT-PCR screening detected PRAME expression in 93%
      of primary neuroblastoma and 100% of patients with advanced disease. Furthermore,
      RT-PCR and Northern blot analysis showed a highly significant association of
      PRAME expression with both higher tumor stage (P < 0.01) and the age of patients
      at diagnosis (P < 0.01). Finally, precise quantification of PRAME expression by
      quantitative real-time reverse transcription-PCR displayed significant impact on
      the outcome of patients. CONCLUSIONS: PRAME expression in neuroblastoma is
      extraordinarily common and was universally seen in patients with advanced-stage
      disease in our study. Furthermore, significant impact of PRAME expression on the
      outcome of patients was shown. Thus, PRAME may present a particularly attractive
      target for immunotherapeutic strategies in neuroblastoma.

PMID- 15240517
TI  - Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in
      non-small cell lung cancer.
AB  - We immunohistochemically examined 12 core proteins involved in the chromatin
      remodeling machinery using a tissue microarray composed of 150 lung
      adenocarcinoma (AD) and 150 squamous cell carcinoma (SCC) cases. Most of the
      proteins showed nuclear staining, whereas some also showed cytoplasmic or
      membranous staining. When the expression patterns of all tested antigens were
      considered, proteins with nuclear staining clustered into two major groups.
      Nuclear signals of BRM, Ini-1, retinoblastoma, mSin3A, HDAC1, and HAT1 clustered
      together, whereas nuclear signals of BRG1, BAF155, HDAC2, BAF170, and RbAP48
      formed a second cluster. Additionally, two thirds of the cases on the lung tissue
      array had follow-up information, and survival analysis was performed for each of
      the tested proteins. Positive nuclear BRM (N-BRM) staining correlated with a
      favorable prognosis in SCC and AD patients with a 5 year-survival of 53.5%
      compared with 32.3% for those whose tumors were negative for N-BRM (P = 0.015).
      Furthermore, patients whose tumors stained positive for both N-BRM and nuclear
      BRG1 had a 5 year-survival of 72% compared with 33.6% (P = 0.013) for those whose
      tumors were positive for either or negative for both markers. In contrast,
      membranous BRM (M-BRM) staining correlated with a poorer prognosis in AD patients
      with a 5 year-survival of 16.7% compared with those without M-BRM staining
      (38.1%; P = 0.016). These results support the notion that BRM and BRG1
      participate in two distinct chromosome remodeling complexes that are functionally
      complementary and that the nuclear presence of BRM, its coexpression with nuclear
      BRG1, and the altered cellular localization of BRM (M-BRM) are useful markers for
      non-small cell lung cancer prognosis.

PMID- 15240518
TI  - Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer.
AB  - PURPOSE: To evaluate leptin and leptin receptor (OB-R) expression in human breast
      cancer and determine whether it could be effective for the prevention and
      treatment of breast cancer. EXPERIMENTAL DESIGN: Immunohistochemical staining
      using specific antibodies was used to evaluate the protein expression of leptin
      and OB-R in 76 invasive ductal carcinomas and 32 samples of corresponding normal
      mammary gland, and the relationship between the expression of OB-R and leptin and
      clinicopathological features was analyzed. RESULTS: Normal mammary epithelial
      cells did not express a significant level of Ob-R, whereas carcinoma cells showed
      positive staining for OB-R in 63 (83%) cases. Both normal epithelial cells and
      carcinoma cells expressed a significant level of leptin. However, overexpression
      of leptin, as determined by staining intensity, was observed in 70 cancers (92%)
      but in no normal epithelium. The expression of OB-R showed a significant
      correlation with the level of leptin expression. Interestingly, distant
      metastasis was detected in 21 (34%) of 61 OB-R-positive tumors with leptin
      overexpression, but in none of the 15 tumors that lacked OB-R expression or
      leptin overexpression (P < 0.05). Consequently, patients with the former tumors
      showed significantly lower survival than those with the latter. CONCLUSIONS:
      Leptin may have a promoting effect on the carcinogenesis and metastasis of breast
      cancer, possibly in an autocrine manner. Functional inhibition of leptin may be
      effective for the prevention and treatment of breast cancer.

PMID- 15240519
TI  - Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in
      hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is the fifth most common cancer around
      the world. Although several therapeutic approaches for treatment of HCC are
      available, survival rates for HCC patients are still very poor because of
      inefficient treatment options. For HCC, as well as other tumors, antigen-specific
      immunotherapy remains a viable approach that is dependent on the definition of
      tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen
      family, is one possible candidate for a tumor-specific antigen in HCC. The aim of
      this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma.
      EXPERIMENTAL DESIGN: Sera samples from 189 HCC patients were analyzed for NY-ESO
      1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA
      expression in HCC tissue. Selected patients were followed for up to 3 years to
      correlate their immune response with their clinical course of events. NY-ESO-1
      specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were
      analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated. RESULTS:
      Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189
      patients showed NY-ESO-1-specific antibody responses. These humoral immune
      responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell
      responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of
      NY-ESO-1-expressing tumors. CONCLUSIONS: This is the first report of a
      spontaneous immune response in HCC patients to a known tumor-specific antigen, NY
      ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for
      the treatment of HCC.

PMID- 15240520
TI  - A cox-2 promoter-based replication-selective adenoviral vector to target the cox
      2-expressing human bladder cancer cells.
AB  - PURPOSE: Cyclooxygenase-2 (Cox-2), an enzyme that catalyzes the synthesis of
      prostaglandins, is overexpressed in a variety of premalignant and malignant
      conditions, including urinary bladder cancer. In the present study, we examined
      the feasibility of using Cox-2 promoter-based replication-selective adenovirus
      for targeting bladder cancer cells that express Cox-2 transcriptional activity.
      EXPERIMENTAL DESIGN: A series of human cancer cell lines, including three bladder
      cancer cell lines (KK47, T24, and 5637), were evaluated for their Cox-2 and CAR
      (the Coxsackievirus and adenovirus receptor) mRNA expression levels by
      quantitative real-time PCR. AdE3-cox2-327, a replication-selective adenovirus in
      which the expression of E1a is controlled by the Cox-2 promoter, was generated,
      and its tissue-specific activity was tested in vitro and in vivo. RESULTS: Three
      bladder cancer cell lines express higher levels of Cox-2 mRNA than does the human
      prostate cancer cell line PC3, the primary cultured human benign prostatic
      fibroblast, PF cells, and the human colon cancer cell line Colo320. Relatively
      higher expression of CAR mRNA was detected in the KK47, 5637, respectively, and
      Colo320 than in the T24, PC-3, and PF cells. In vitro assays revealed significant
      growth suppression of both Cox-2- and CAR-expressing bladder cancer cells KK47
      and 5637 in comparison with the other cells that lack Cox-2 expression and/or CAR
      expression. CONCLUSIONS: The present study demonstrated both specificity and
      efficacy of AdE3-cox2-327, a selectively replicated adenovirus, toward the Cox-2
      expressing bladder cancer cells in vitro and in vivo. We also found that CAR
      expression in the target cancer cells is an important factor for the efficacy of
      selectively replicated adenovirus-based gene therapy.

PMID- 15240521
TI  - Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of
      gastric cancer by inhibiting angiogenesis.
AB  - PURPOSE: It has been recently shown that the catecholamine neurotransmitter
      dopamine (DA) strongly and selectively inhibits vascular permeability
      factor/vascular endothelial growth factor (VPF/VEGF)-induced angiogenesis.
      Gastric cancer is highly angiogenic and is dependent on VEGF for its growth and
      progression. Because substantial amounts of DA present in normal stomach tissues
      has been implicated in several gastric functions, we therefore investigated the
      role, if any, of this neurotransmitter in the growth and progression of gastric
      cancer. EXPERIMENTAL DESIGN: Initially, the status of DA and tyrosine
      hydroxylase, the rate-limiting enzyme required for DA synthesis, were determined
      in human gastric cancer tissues and in N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG)-induced gastric cancer tissues of rats. On the basis of our observation of
      inverse correlation between stomach DA and gastric cancer growth, we determined
      the effect of pharmacological dose of DA on the angiogenesis and growth of MNNG
      induced gastric cancer in rats and Hs746T human gastric cancer in nude mice.
      RESULTS: DA and tyrosine hydroxylase were absent in both human and rat gastric
      cancer tissues. On the contrary, a low nontoxic pharmacological dose of DA
      significantly retarded tumor angiogenesis by inhibiting VEGFR-2 phosphorylation
      in tumor endothelial cells, which expressed DA D(2) receptors. This action of DA
      was associated with the growth inhibition of both MNNG-induced rat malignant
      gastric tumors and xenotransplanted human gastric cancer in nude mice.
      CONCLUSIONS: Our study demonstrates that there is an inverse correlation between
      endogenous stomach DA and gastric cancer and indicates that DA already in
      clinical use for other purposes might have a role as an antiangiogenic agent in
      the treatment of gastric cancer.

PMID- 15240522
TI  - The dl1520 virus is found preferentially in tumor tissue after direct
      intratumoral injection in oral carcinoma.
AB  - PURPOSE: dl1520 (also known as Onyx-015) is an E1B-deleted adenovirus designed to
      selectively lyse p53-deficient cancer cells. Clinical trials involving patients
      with recurrent squamous cell carcinoma of the head and neck have shown clinical
      efficacy, but no direct evidence as to the tumor or p53 selectivity of the virus
      was demonstrated. We wanted to determine whether dl1520 is selective for survival
      and replication within tumor tissue after direct injection and whether this is
      determined by p53 status of the tissues. We also wanted to ascertain whether the
      virus has any macroscopic effect on normal tissue. EXPERIMENTAL DESIGN: An open
      label Phase II trial was devised in which a fixed dose of the virus was
      administered to 15 patients via a direct intertumoral injection before surgery
      for untreated oral squamous cell carcinoma. The agent was also delivered into an
      area of adjacent normal buccal mucosa. Specimens of the excised tumor and of
      biopsies of the injected normal tissue were assessed for viral presence and p53
      status. RESULTS: We demonstrated that the virus replicates selectively in tumor
      as opposed to normal tissue after this direct injection. It was not possible to
      determine whether this selectivity was p53 related. It was found that dl1520
      triggers an early rise in apoptosis levels in injected normal tissues. No adverse
      effects of viral injection were noted. CONCLUSIONS: This is the first report of
      injection of dl1520 into previously untreated squamous cell cancer. The data
      support the concept that dl1520 is replication deficient in normal, compared with
      cancerous, tissues and has potential as a selective anticancer agent against
      tumor tissues.

PMID- 15240524
TI  - Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced
      non-small-cell lung cancer: a multi-institutional phase II trial.
AB  - PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment
      using concurrent radiotherapy with cisplatin plus UFT, which is comprised of
      uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC)
      patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable
      stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d
      tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was
      administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was
      delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and
      eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74;
      performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was
      observed in two patients and a partial response in 54 patients, and the overall
      response rate was 81% (95% confidence interval; 70-89%). The median survival, the
      1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade
      3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological
      toxicities were only reported in three patients with nausea, two with esophagitis
      and one with pneumonitis whereas no grade 4 non-hematological toxicity was
      observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is
      considered to be a feasible and effective treatment for locally advanced NSCLC
      patients. Additional study of this concurrent chemoradiotherapy is warranted.

PMID- 15240523
TI  - A phase I study of cantuzumab mertansine administered as a single intravenous
      infusion once weekly in patients with advanced solid tumors.
AB  - PURPOSE: The purpose is to determine the maximum-tolerated dose, assess the
      toxicities, characterize the pharmacokinetic behavior, and seek preliminary
      evidence of biological activity of cantuzumab mertansine when administered as a
      weekly i.v. infusion without interruption. EXPERIMENTAL DESIGN: Patients with
      incurable solid tumors that expressed the target antigen for cantuzumab
      mertansine, CanAg, were treated with doses of cantuzumab mertansine ranging from
      40 to 138 mg/m(2). The maximum-tolerated dose was defined as the highest dose at
      which no more than 1 of 6 patients experienced dose-limiting toxicity. Plasma
      concentrations of cantuzumab mertansine and total humanized antibody were
      determined, and area under the plasma concentration-time curve (to the last
      measured concentration) was calculated. RESULTS: Thirty-nine patients received a
      total of 280 weekly doses of cantuzumab mertansine. Acute, transient elevation of
      the hepatic transaminases and reversible fatigue were identified as the dose
      limiting toxicities at the highest dose level. The maximum-tolerated dose was
      determined to be 115 mg/m(2)/week. Evidence of clinical activity was noted in 3
      patients. Pharmacokinetic analyses revealed that the pharmacokinetic variability
      was moderate, without evidence of dose dependency. Furthermore, the drug had a
      long terminal half-life ( approximately 40 h). CONCLUSIONS: This study identified
      a safe and tolerable dose of the novel immunoconjugate prodrug cantuzumab
      mertansine. The evidence of antitumor activity suggests that additional clinical
      development is warranted, with a focus on tumors that express high levels of
      CanAg and which are known to be sensitive to antimicrotubule agents.

PMID- 15240525
TI  - A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14
      day oral twice daily schedule every 4 weeks in patients with solid tumors.
AB  - PURPOSE: This is a dose-finding Phase I study of oral Ro 31-7453, a new class of
      antimitotic drug with promising preclinical activity in several chemoresistant
      models. EXPERIMENTAL DESIGN: Two schedules of oral Ro 31-7453 (every 12 h) given
      for either 7 or 14 consecutive days repeated every 4 weeks were explored
      consecutively. RESULTS: Thirty-seven patients with refractory cancer entered the
      study (14 on the 7-day schedule and 23 on the 14-day schedule). Median age was 63
      years (range, 40-77 years), and median Karnofsky performance status was 80
      (range, 60-100); the most frequent diagnosis was colorectal carcinoma (16
      patients). Dose levels of 100, 200, 240, and 280 mg/m(2) twice daily (bid) for 7
      days and 70, 100, 125, and 150 mg/m(2) bid for 14 days were explored. A total of
      110 cycles were administered, the median number of cycles received was 3 (range,
      1-7); six patients completed 6 or more cycles. Myelosuppression and mucositis
      were dose-limiting with both schedules. Fatigue and gastrointestinal toxicities
      other than mucositis were frequent but generally mild. The maximum tolerated
      doses were 200 mg/m(2) bid and 125 mg/m(2) bid for the 7- and 14-day schedules,
      respectively. Pharmacokinetic analysis showed rapid absorption and metabolism.
      The area under the concentration-time curve and trough concentrations of Ro 31
      7453 and two active metabolites appeared dose proportional with a t(1/2) of
      approximately 9 h and a t(max) of approximately 4 h. One patient with pretreated
      lung cancer had a partial response. CONCLUSIONS: Both Ro 31-7453 regimens were
      feasible, but the 14-day schedule at the recommended dose of 125 mg/m(2) bid was
      selected for further monotherapy Phase II evaluation because of its higher
      preclinical activity. This regimen is convenient, well tolerated, and has a
      favorable pharmacokinetic profile.

PMID- 15240526
TI  - Gefitinib (ZD1839) monotherapy as a salvage regimen for previously treated
      advanced non-small cell lung cancer.
AB  - PURPOSE: A worldwide compassionate-use program has enabled >42,000 patients with
      advanced non-small cell lung cancer (NSCLC) to receive gefitinib treatment. Here
      we report the outcome of gefitinib therapy in patients who enrolled in the
      "Iressa" Expanded Access Program at the Samsung Medical Center. EXPERIMENTAL
      DESIGN: Patients with advanced or metastatic NSCLC who had progressed after prior
      systemic chemotherapy and for whom no other treatment option was available were
      eligible to receive gefitinib treatment as part of the Expanded Access Program. A
      post hoc assessment of potential prognostic factors for response and survival was
      performed by multivariate analysis. RESULTS: All 111 evaluable patients had stage
      IV disease; most patients had a baseline performance status of 2 [n = 52 (47%)]
      or 3 [n = 18 (16%)] and had received >/=2 prior chemotherapy regimens (56%). The
      objective response rate was 26%, the disease control rate (measured over >/=8
      weeks) was 40%, and the 1-year survival rate was 44%. Adenocarcinoma histology
      was associated with better response and disease control rates, and a performance
      status of 0-2 was also associated with a better disease control rate. Both of
      these factors, as well as female gender, were significantly associated with
      longer survival. Gefitinib was well tolerated; the most common adverse event was
      grade 1 skin rash. CONCLUSIONS: Gefitinib demonstrated significant antitumor
      activity and a favorable tolerability profile in this series of NSCLC patients
      with poor prognosis.

PMID- 15240527
TI  - A two-by-two factorial trial comparing oral with transdermal estrogen therapy and
      fenretinide with placebo on breast cancer biomarkers.
AB  - PURPOSE: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate
      (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol
      (E2) and MPA is less known. Fenretinide may decrease second breast malignancies
      in premenopausal women but not in postmenopausal women, suggesting a hormone
      sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth
      factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex
      hormone binding-globulin, and computerized mammographic percent density during
      oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo.
      EXPERIMENTAL DESIGN: A total of 226 recent postmenopausal healthy women were
      randomly assigned in a two-by-two factorial design to either oral CEE 0.625
      mg/day (n = 111) or transdermal E2, 50 microg/day (n = 115) and to fenretinide
      100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment
      effects were investigated by the Kruskall-Wallis test and analysis of covariance.
      P values were two-sided. RESULTS: After 12 months, oral CEE decreased IGF-I by
      26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding
      globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change
      occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased
      IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an
      absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without
      differences between groups (P = 0.39). CONCLUSIONS: Oral CEE has more favorable
      changes than transdermal E2 on circulating breast cancer risk biomarkers but
      gives similar effects on mammographic density. Fenretinide exerted little
      modulation on most biomarkers. The clinical implications of these findings
      require additional studies.

PMID- 15240528
TI  - Combination of somatostatin analog, dexamethasone, and standard androgen ablation
      therapy in stage D3 prostate cancer patients with bone metastases.
AB  - PURPOSE: Androgen ablation-refractory prostate cancer patients (stage D3) develop
      painful bone metastases and limited responsiveness to conventional therapies,
      hence the lack of universally accepted "gold standard" treatment for this poor
      prognosis clinical setting. We tested the safety and efficacy in stage D3
      patients of the combination hormonal therapy, which combines administration of
      somatostatin analog and dexamethasone with standard androgen ablation monotherapy
      (luteinizing-hormone releasing-hormone analog or orchiectomy). EXPERIMENTAL
      DESIGN: Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/-
      5.9 years) continued receiving androgen ablation therapy in combination with oral
      dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg
      daily by the 4th month, with 1 mg daily maintenance dose thereafter) and
      somatostatin analog (20 mg octreotide i.m. injections every 28 days). RESULTS:
      Twenty-three of 38 patients (60.5%) receiving this combination regimen had
      partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%)
      had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of
      patients, their serum PSA levels decreased with treatment but did not return to
      their respective baselines until the end of follow-up (or death from non-prostate
      cancer-related causes). The median time-to-return to baseline PSA was 12 months
      (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5
      9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months),
      and median prostate cancer-specific overall survival (defined as time from onset
      of combination therapy until prostate cancer-related death) was 16.0 months (95%
      CI, 11.9-20.1 months). All patients reported significant and durable improvement
      of bone pain and performance status (for a median duration of 14 months; 95% CI,
      9-19 months), without major treatment-related side effects. We observed a
      statistically significant (P < 0.01) reduction in serum insulin-like growth
      factor-1 levels at response to the combination therapy. T levels remained
      suppressed within castration levels at baseline and throughout therapy, including
      relapse. CONCLUSION: The combination therapy of dexamethasone plus somatostatin
      analog and standard androgen ablation manipulation produces objective clinical
      responses and symptomatic improvement in androgen ablation-refractory refractory
      prostate cancer patients.

PMID- 15240529
TI  - Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients
      with refractory malignancies.
AB  - PURPOSE: Atrasentan is an orally bioavailable selective antagonist of the
      endothelin receptor ET(A). Due to the potential activity of this agent against
      prostate cancer, the majority of subjects enrolled in prior studies had been
      male. This Phase I study sought to determine the toxicity and pharmacokinetics of
      daily atrasentan in a population of both female and male subjects with advanced
      malignancies. EXPERIMENTAL DESIGN: Patients with refractory malignancies received
      atrasentan once daily at doses ranging from 5 mg to 75 mg. At least 3 subjects
      were treated at each dose level before enrollment began at the next higher dose
      level. Enrollment for specific dose levels was expanded if any subject
      experienced serious drug-related toxicity. Plasma concentration profiles for
      atrasentan were determined after dosing on days 1 and 28. RESULTS: Thirty-five
      patients received atrasentan at doses from 5 mg to 75 mg. The most frequent drug
      related adverse events were headache (60%), rhinitis (49%), and peripheral edema
      (31%). These toxicities were mild to moderate in severity and reversible on
      cessation of treatment. Dose escalation was stopped at the 75-mg dose level due
      to the occurrence of three severe adverse events (2 hyponatremia and 1
      hypotension). Atrasentan was rapidly absorbed after oral administration; mean
      time to maximum observed concentration ranged from 0.3 to 1.7 h. Terminal
      elimination half-life averaged 26 h. No significant difference between sexes was
      found in any atrasentan pharmacokinetic parameter tested, including maximum
      observed plasma concentration, time to maximum observed concentration, minimum
      observed plasma concentration, area under the plasma concentration-time curve,
      and elimination rate constant. CONCLUSIONS: Atrasentan is well tolerated in both
      female and male cancer patients at doses of up to 60 mg/day with dose-limiting
      toxicity observed at 75 mg/day. The most frequently observed toxicities were
      headache, rhinitis, and edema. There was no statistically significant difference
      in atrasentan pharmacokinetics between sexes.

PMID- 15240530
TI  - Cytochrome p450 and glutathione transferase expression in squamous cell cancer.
AB  - PURPOSE: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme
      systems modulate the carcinogenic effects of tobacco. Therefore, the expression
      of these enzymes may be in part responsible for the observed interindividual and
      inter-racial differences in the risk of development of squamous cell carcinoma of
      the head and neck (SCCHN). The first aim of this study was to evaluate the
      feasibility of measuring the expression of the CYP and GST in target tissue from
      the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1,
      and 3A4 in squamous epithelium from African-American and Caucasian pediatric
      patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and
      GST-pi on the p16 expression in patients with SCCHN. EXPERIMENTAL DESIGN: The
      expression of CYP 1A1, 2E1, 3A4, GST-pi, and p16 was quantified by
      immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue
      from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1,
      2E1, 3A4, GST-pi, and p16 was determined in 46 resected SCCHN patients. RESULTS:
      Large interindividual variability in the expression of these enzymes was observed
      in the pediatric and adult populations. No significant difference was observed in
      CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients.
      There was no correlation between p16 and enzyme expression in patients with
      SCCHN. CONCLUSION: Evaluation of CYP expression in the target tissue of interest
      is feasible. The clinical significance of CYPs and GST-pi alterations in the risk
      of developing SCCHN will need to be investigated in larger trials.

PMID- 15240531
TI  - Mouse mammary tumor-like virus is associated with p53 nuclear accumulation and
      progesterone receptor positivity but not estrogen positivity in human female
      breast cancer.
AB  - PURPOSE: The purpose is to compare the presence of proteins with known
      associations with breast cancer-progesterone receptor (PgR), estrogen receptor,
      and p53, with the prevalence of mouse mammary tumor virus (MMTV)-like DNA
      sequences in human female breast cancers. EXPERIMENTAL DESIGN: A cohort of 128
      Australian female breast cancers were screened for MMTV-like DNA sequences using
      PCR. The presence of PgR, estrogen receptor, and nuclear accumulation of p53
      protein was assessed in the same samples using immunohistochemical staining.
      RESULTS: Nuclear accumulation of p53 was significantly more prevalent (P = 0.05)
      in archival human breast cancers containing MMTV-like DNA sequences. The presence
      of progesterone receptor was significantly higher in MMTV-positive than MMTV
      negative breast cancers (P = 0.01). No correlation between estrogen receptor and
      MMTV-like DNA sequences was found. CONCLUSIONS: MMTV causes breast cancer in
      mice, and hormones up-regulate expression of virus in mice mammary tissue. It is
      unknown if this is the case in human breast cancers shown to contain DNA of MMTV
      like viruses. The positive association between MMTV-like DNA sequences and PgR
      indicates hormones and MMTV may play a role in human breast cancer. Mutations of
      the tumor suppressor gene p53 are common in human breast cancer and are
      associated with higher grades of cancer. The association of MMTV-like DNA
      sequences with higher grades of cancer, and the positive association between p53
      and MMTV-like DNA sequences clearly warrant additional investigation.

PMID- 15240532
TI  - The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts
      poor survival for ovarian cancer patients.
AB  - Aberrant epigenetic regulation, such as CpG island methylation and associated
      transcriptional silencing of genes, has been implicated in a variety of human
      diseases, including cancer. Methylation of genes involved in apoptosis, including
      the DNA mismatch repair (MMR) gene hMLH1, can occur in tumor models of resistance
      to chemotherapeutic drugs. However, the relevance for acquired resistance to
      chemotherapy of patients' tumors remains unsubstantiated. Plasma DNA from cancer
      patients, including those with ovarian cancer, often contains identical DNA
      changes as the tumor and provides a means to monitor CpG island methylation
      changes. We have examined plasma DNA of patients with epithelial ovarian cancer
      enrolled in the SCOTROC1 Phase III clinical trial for methylation of the hMLH1
      CpG island before carboplatin/taxoid chemotherapy and at relapse. Methylation of
      hMLH1 is increased at relapse, and 25% (34 of 138) of relapse samples have hMLH1
      methylation that is not detected in matched prechemotherapy plasma samples.
      Furthermore, hMLH1 methylation is significantly associated with increased
      microsatellite instability in plasma DNA at relapse, providing an independent
      measure of function of the MMR pathway. Acquisition of hMLH1 methylation in
      plasma DNA at relapse predicts poor overall survival of patients, independent
      from time to progression and age (hazard ratio, 1.99; 95% confidence interval,
      1.20-3.30; P = 0.007). These data support the clinical relevance of acquired
      hMLH1 methylation and concomitant loss of DNA MMR after chemotherapy of ovarian
      cancer patients. DNA methylation changes in plasma provide the potential to
      define patterns of methylation during therapy and identify those patient
      populations who would be suitable for novel epigenetic therapies.

PMID- 15240533
TI  - Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in
      metaplastic ovarian epithelium and ovarian cancer.
AB  - PURPOSE: A better understanding of the molecular pathways underlying the
      development of epithelial ovarian cancer (EOC) is critical to identify ovarian
      tumor markers for use in diagnostic or therapeutic applications. The aims of this
      study were to integrate the results from 14 transcript profiling studies of EOC
      to identify novel biomarkers and to examine their expression in early and late
      stages of the disease. EXPERIMENTAL DESIGN: A database incorporating genes
      identified as being highly up-regulated in each study was constructed. Candidate
      tumor markers were selected from genes that overlapped between studies and by
      evidence of surface membrane or secreted expression. The expression patterns of
      three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3
      (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell
      adhesion, were evaluated in a cohort of 158 primary EOC using
      immunohistochemistry. RESULTS: We confirmed that these genes are highly
      overexpressed in all histological subtypes of EOC compared with normal ovarian
      surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC.
      Furthermore, we determined that these genes are also expressed in ovarian
      epithelial inclusion cysts, a site of metaplastic changes within the normal
      ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an
      association between low CLDN3 expression and poor patient outcome was also
      observed. CONCLUSIONS: These results suggest that up-regulation of DDR1, CLDN3,
      and epithelial cell adhesion molecule are early events in the development of EOC
      and have potential application in the early detection of disease.

PMID- 15240534
TI  - M34 actin regulatory protein is a sensitive diagnostic marker for early- and late
      stage mammary carcinomas.
AB  - PURPOSE: At present, there is no available molecular marker that reliably detects
      the earliest stages of epithelial transformation in the majority of patients
      affected with incipient breast carcinoma. Here we introduce M34 protein, a
      mammalian actin filament regulatory protein, as a highly sensitive and easily
      detected positive cellular marker for both early and late stages of breast
      carcinoma. EXPERIMENTAL DESIGN: In this study, 24 human lactation duct neoplasms
      from postmenopausal women, including fibroadenoma, ductal carcinoma in situ,
      intraductal lobular papilloma, and metastatic adenocarcinoma, were analyzed for
      the presence of M34 protein by histochemical staining of paraffin and fresh
      frozen sections. RESULTS: All 24 neoplasias tested positive for M34, whereas none
      of the 4 normal breast tissues stained for the protein. M34 identification was
      strongly positive for transformed epithelium in all tumor types tested. Twelve
      precancerous lesions of fibroadenoma (n = 4), intraductal papilloma (n = 4), and
      incipient ductal carcinoma in situ (n = 4) all showed high levels of M34
      staining, suggesting that precancerous tumors, as well as the earliest stages of
      mammary carcinoma, can be sensitively detected. Furthermore, anti-M34 antibody
      selectively stained all 12 advanced-stage metastatic adenocarcinoma cell masses
      and micrometastases in axillary lymph nodes tested. Single-cell micrometastases
      embedded in connective tissue or lymph node parenchyma could be clearly resolved
      by M34 with horseradish peroxidase staining. Lymphocytes, normal ductal
      endothelium, and vascular endothelial cells were M34-negative, as were muscle,
      nerve, and adipose tissues. Low-level M34 staining was detected in connective
      tissue fibroblasts, macrophages, and neutrophils. CONCLUSIONS: To our knowledge,
      no previously reported markers have shown high sensitivity of detection for both
      the earliest and most advanced stages of breast carcinoma. Consequently, M34
      appears uniquely suited for diagnosis of the earliest stages of lactation duct
      transformation as well as for advanced-stage mammary carcinoma metastases in
      surgical margins and axillary lymph nodes.

PMID- 15240535
TI  - Detection of lymph node micrometastases by gene promoter hypermethylation in
      samples obtained by endosonography- guided fine-needle aspiration biopsy.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a
      fundamental procedure for gastrointestinal and lung cancer staging. However,
      there is growing evidence that micrometastases are present in lymph nodes, which
      cannot be detected with standard pathological methods. The aim of this study was
      to evaluate whether hypermethylation gene promoter analysis was feasible on
      samples obtained by EUS-FNA from lymph nodes, as well as to establish the
      usefulness of this strategy for the detection of micrometastases in patients with
      gastrointestinal and non-small cell lung cancer. Suspicious lymph nodes based on
      EUS findings from consecutive patients with esophageal, gastric, rectal, and non
      small cell lung cancer were sampled by EUS-FNA. Hypermethylation analysis of the
      MGMT, p16(INK4a), and p14(ARF) gene promoter CpG islands were performed by
      methylation-specific PCR. Effectiveness of conventional cytology, methylation
      analysis, and their combination were established with respect to the definitive
      diagnosis. Twenty-seven patients were included, thus representing a total of 42
      lymph nodes (esophageal cancer, n = 11; rectal cancer, n = 7; gastric cancer, n =
      3; and lung cancer, n = 21). According to definitive diagnosis, 21 (50%)
      corresponded to metastatic lymph nodes. Sensitivity, specificity, and overall
      accuracy of conventional cytology were 76%, 100%, and 88%, respectively, whereas
      the corresponding values for the methylation analysis were 81%, 67%, and 74%,
      respectively. Combination of both techniques increased sensitivity (90%) but
      decreased specificity (67%) with respect to conventional cytology. In conclusion,
      it is feasible to detect occult neoplastic cells in EUS-FNA samples by
      hypermethylation gene promoter analysis. Moreover, addition of methylation
      analysis to conventional cytology may increase its sensitivity at the expenses of
      a decrease in its specificity.

PMID- 15240536
TI  - Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial
      carcinoma.
AB  - PURPOSE: CTLs are a prominent immune component infiltrating many solid tumors.
      These cells are considered to be a manifestation of host-immune response to the
      tumor; however, their prognostic significance remains a subject of considerable
      debate. The objective of this study was to evaluate the distribution pattern and
      prognostic value of CD8(+) T cells in endometrial carcinoma. EXPERIMENTAL DESIGN:
      We studied 90 cases of endometrial carcinoma, including 75 endometrioid and 15
      papillary serous carcinomas. Immunohistochemical staining for CD8 and granzyme B
      was performed on paraffin-embedded sections. The number of immunohistochemically
      staining CD8(+) T cells was enumerated in the following four regions: lymphocytes
      infiltrating the tumor epithelium at the invasive border, within the underlying
      tumor stroma, within the superficial tumor epithelium, and in the perivascular
      areas of the myometrium. RESULTS: Patients with >10 CD8(+) T lymphocytes/high
      power field within the tumor epithelium at the invasive border displayed improved
      overall survival compared with patients with fewer intraepithelial CD8(+) T
      lymphocytes (87 and 50%, respectively; P = 0.027). Multivariate analysis revealed
      that stage, vascular invasion, grade, and the number of intraepithelial CD8(+) T
      lymphocytes at the invasive border were the only independent predictors of
      survival (P < 0.0001, P = 0.001, P = 0.011, and P = 0.025, respectively).
      Granzyme B(+) cytoplasmatic granules were detected in a high proportion of CTLs,
      confirming their activated cytotoxic phenotype. CONCLUSIONS: Our study
      demonstrates for the first time that increased numbers of CTLs at the invasive
      border may be a reliable independent prognostic factor of survival in patients
      with endometrial carcinoma.

PMID- 15240537
TI  - Predicting early failure after adjuvant chemotherapy in high-risk breast cancer
      patients with extensive lymph node involvement.
AB  - PURPOSE: There is limited knowledge of risk factors for breast cancer recurrence
      within 2 years. This study aimed to predict early failure and identify high-risk
      patients for prognostic and therapeutic purposes. EXPERIMENTAL DESIGN: We studied
      739 patients from a randomized trial who were <56 years of age and had >/=4 or
      more positive lymph nodes, no distant metastases, and no previous other
      malignancies. After complete surgical treatment, patients received conventional
      dose anthracycline-based chemotherapy or a high-dose scheme of anthracycline
      based plus alkylating chemotherapy. We assessed clinical and (immuno)histological
      parameters to predict recurrence within 2 years. RESULTS: Early failure occurred
      in 19% (n = 137). Median survival after early failure was limited to 0.7 year.
      Estrogen and progesterone receptor negativity and visceral relapse predicted poor
      prognosis. Early failure was associated with young age, large tumors, high
      histological grade, angio-invasion, apical node metastasis, and >/=10 involved
      nodes. Estrogen receptor, progesterone receptor, and p27 negativity; HER2
      overexpression; and p53 positivity also predicted early failure. The surgical or
      chemotherapy regimen and histological type did not. The same parameters except
      tumor size were associated with early death. Grade III, >/=10 involved nodes, and
      estrogen receptor negativity were independently associated with early failure and
      together identified a subset of patients (7%) with 3-fold increased early failure
      and 5-fold increased early death. CONCLUSIONS: Early failure is associated with
      poor survival. The combination of three commonly determined parameters
      constitutes a strong predictive model for early failure and death.

PMID- 15240538
TI  - Carbonic anhydrase IX as a marker for poor prognosis in soft tissue sarcoma.
AB  - PURPOSE: Hypoxia is associated with malignant progression and poor outcome in
      several human tumors, including soft tissue sarcoma. Recent studies have
      suggested that carbonic anhydrase (CA) IX is an intrinsic marker of hypoxia, and
      that CA IX correlates with poor prognosis in several types of carcinoma. The aim
      of this study was to quantify the extent of CA IX expression and to investigate
      whether CA IX is a marker for poor prognosis in soft tissue sarcoma patients at
      high risk of developing metastasis. EXPERIMENTAL DESIGN: Archival paraffin
      embedded blocks were retrieved from 47 patients with deep, large, high-grade soft
      tissue sarcoma. Sections from two separate and representative tumor areas were
      immunostained for CA IX, and the CA IX-positive area fraction was quantified by
      image analysis, excluding areas of normal stroma and necrosis that were
      identified from serial H&E-stained sections. Patients were then subject to
      survival analysis. RESULTS: CA IX-positive area fractions of viable tumor tissue
      varied significantly between tumors (range, 0-0.23; median, 0.004), with positive
      membranous CA IX staining in 66% (31 of 47) of the tumors. Patients with CA IX
      positive tumors had a significantly lower disease-specific and overall survival
      than patients with CA IX-negative tumors (P = 0.033 and P = 0.044, respectively).
      CONCLUSIONS: These data suggest that CA IX, a potential intrinsic marker of
      hypoxia, predicts for poor prognosis in patients with deep, large, high-grade
      soft tissue sarcoma. Larger studies are required to determine whether CA IX has
      independent prognostic value in this group of tumors.

PMID- 15240539
TI  - The A3 adenosine receptor is highly expressed in tumor versus normal cells:
      potential target for tumor growth inhibition.
AB  - PURPOSE: A(3) adenosine receptor (A(3)AR) activation was shown to inhibit the
      growth of various tumor cells via the down-regulation of nuclear factor kappaB
      and cyclin D1. To additionally elucidate whether A(3)AR is a specific target, a
      survey of its expression in tumor versus adjacent normal cells was conducted.
      EXPERIMENTAL DESIGN: A(3)AR mRNA expression in various tumor tissues was tested
      in paraffin-embedded slides using reverse transcription-PCR analysis. A
      comparison with A(3)AR expression in the relevant adjacent normal tissue or
      regional lymph node metastasis was performed. In addition, A(3)AR protein
      expression was studied in fresh tumors and was correlated with that of the
      adjacent normal tissue. RESULTS: Reverse transcription-PCR analysis of colon and
      breast carcinoma tissues showed higher A(3)AR expression in the tumor versus
      adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed
      that the lymph node metastasis expressed even more A(3)AR mRNA than the primary
      tumor tissue. Protein analysis of A(3)AR expression in fresh tumors derived from
      colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A(3)AR
      expression in the tumor versus normal adjacent tissue, respectively. The high
      A(3)AR expression level in the tumor tissues was associated with elevated nuclear
      factor kappaB and cyclin D1 levels. High A(3)AR mRNA expression was also
      demonstrated in other solid tumor types. CONCLUSIONS: Primary and metastatic
      tumor tissues highly express A(3)AR indicating that high receptor expression is a
      characteristic of solid tumors. These findings and our previous data suggest
      A(3)AR as a potential target for tumor growth inhibition.

PMID- 15240540
TI  - Simultaneous expression of furin and vascular endothelial growth factor in human
      oral tongue squamous cell carcinoma progression.
AB  - PURPOSE: Squamous cell carcinoma (SCC) of the tongue is a common malignancy of
      the oral cavity. Furin convertase activates several precursor matrix
      metalloproteinases involved in the degradation of the extracellular matrix. The
      pattern of expression of furin and vascular endothelial growth factor-C (VEGF-C),
      two key molecules in neoplasm development, was examined during the progression
      from normal epithelium to invasive SCC. EXPERIMENTAL DESIGN: We evaluated furin
      and VEGF-C expression and microvessel density (MVD) by immunohistochemistry in
      human tongue sections harboring normal epithelium, dysplastic epithelium, and/or
      SCC. Sections from 46 glossectomy specimens were assessed for furin expression. A
      selected group of 15 cases, each containing normal epithelium, precursor lesions,
      and invasive SCC, were further studied for furin and VEGF-C expression and MVD
      quantification. We also evaluated the pattern of furin expression and VEGF-C
      processing by Western blot analysis in three SCC cell lines with different
      degrees of aggressiveness. RESULTS: Furin and VEGF-C expression was notably
      higher in most precursor lesions and SCCs than in normal epithelia. Approximately
      60% (n = 26) and 100% (n = 15) of the normal epithelia showed low-intensity
      staining for furin and VEGF-C, respectively. Intense staining for furin and VEGF
      C was detected in approximately 80% (n = 34) and 100% (n = 15) of the SCCs,
      respectively. A significant correlation was seen between the expression of these
      two markers (Spearman's test, P < 0.00002). We found a statistically significant
      increase in MVD when either dysplasia (432 +/- 19.06; P < 0.05) or SCC (546 +/-
      17.24) was compared with normal epithelium (315 +/- 17.27; P < 0.0001). SCC71,
      the most aggressive cell line analyzed, was the one with the highest furin
      expression. This cell line totally processed the VEGF-C proform, whereas the less
      aggressive line SCC9, exhibiting the least furin expression, did not. SCC15, of
      intermediate aggressiveness and furin expression, showed intermediate pro-VEGF-C
      processing. CONCLUSIONS: These findings suggest that furin is a useful marker of
      tumor progression and is responsible for VEGF-C processing. This in turn would
      enhance angiogenesis, leading to increased MVD associated with preinvasive and
      invasive neoplasia.

PMID- 15240541
TI  - Alpha-particle emitting atomic generator (Actinium-225)-labeled trastuzumab
      (herceptin) targeting of breast cancer spheroids: efficacy versus HER2/neu
      expression.
AB  - PURPOSE: The humanized monoclonal antibody, trastuzumab (Herceptin), directed
      against HER2/neu, has been effective in the treatment of breast cancer
      malignancies. However, clinical activity has depended on HER2/neu expression.
      Radiolabeled trastuzumab has been considered previously as a potential agent for
      radioimmunotherapy. The objective of this study was to investigate the efficacy
      of trastuzumab labeled with the alpha-particle emitting atomic generator,
      actinium-225 ((225)Ac), against breast cancer spheroids with different HER2/neu
      expression levels. (225)Ac has a 10-day half-life and a decay scheme yielding
      four alpha-particles. EXPERIMENTAL DESIGN: The breast carcinoma cell lines MCF7,
      MDA-MB-361 (MDA), and BT-474 (BT) with relative HER2/neu expression (by flow
      cytometry) of 1:4:18 were used. Spheroids of these cell lines were incubated with
      different concentrations of (225)Ac-trastuzumab, and spheroid growth was measured
      by light microscopy over a 50-day period. RESULTS: The activity concentration
      required to yield a 50% reduction in spheroid volume at day 35 was 18.1, 1.9, and
      0.6 kBq/ml (490, 52, 14 nCi/ml) for MCF7, MDA, and BT spheroids, respectively.
      MCF7 spheroids continued growing but with a 20-30 day growth delay at 18.5
      kBq/ml. MDA spheroid growth was delayed by 30-40 days at 3.7 kBq/ml; at 18.5
      kBq/ml, 12 of 12 spheroids disaggregated after 70, days and cells remaining from
      each spheroid failed to form colonies within 2 weeks of being transferred to
      adherent dishes. Eight of 10 BT spheroids failed to regrow at 1.85 kBq/ml. All of
      the BT spheroids at activity concentrations 3.7 kBq/ml failed to regrow and to
      form colonies. The radiosensitivity of these three lines as spheroids was
      evaluated as the activity concentration required to reduce the treated to
      untreated spheroid volume ratio to 0.37, denoted DVR(37). An external beam
      radiosensitivity of 2 Gy was found for spheroids of all three of the cell lines.
      After alpha-particle irradiation a DVR(37) of 1.5, 3.0, and 2.0 kBq/ml was
      determined for MCF7, MDA, and BT, respectively. CONCLUSION: These studies suggest
      that (225)Ac-labeled trastuzumab may be a potent therapeutic agent against
      metastatic breast cancer cells exhibiting intermediate to high HER2/neu
      expression.

PMID- 15240542
TI  - Effective photoimmunotherapy of murine colon carcinoma induced by the combination
      of photodynamic therapy and dendritic cells.
AB  - PURPOSE: The unique mechanism of tumor destruction by photodynamic therapy (PDT),
      resulting from apoptotic and necrotic killing of tumor cells accompanied by local
      inflammatory reaction and induction of heat shock proteins (HSPs), prompted us to
      investigate the antitumor effectiveness of the combination of PDT with
      administration of immature dendritic cells (DCs). EXPERIMENTAL DESIGN: Confocal
      microscopy and Western blotting were used to investigate the influence of PDT on
      the induction of apoptosis and expression of HSP expression in C-26 cells.
      Confocal microscopy and flow cytometry studies were used to examine phagocytosis
      of PDT-treated C-26 cells by DCs. Secretion of interleukin (IL)-12 was measured
      with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard
      (51)Cr-release assay. The antitumor effectiveness of PDT in combination with
      administration of DCs was investigated in in vivo model. RESULTS: PDT treatment
      resulted in the induction of apoptotic and necrotic cell death and expression of
      HSP27, HSP60, HSP72/73, HSP90, HO-1, and GRP78 in C-26 cells. Immature DCs
      cocultured with PDT-treated C-26 cells efficiently engulfed killed tumor cells,
      acquired functional features of maturation, and produced substantial amounts of
      IL-12. Inoculation of immature DCs into the PDT-treated tumors resulted in
      effective homing to regional and peripheral lymph nodes and stimulation of
      cytotoxic activity of T and natural killer cells. The combination treatment with
      PDT and administration of DCs produced effective antitumor response. CONCLUSIONS:
      The feasibility and antitumor effectiveness demonstrated in these studies suggest
      that treatment protocols involving the administration of immature DCs in
      combination with PDT may have clinical potential.

PMID- 15240543
TI  - Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.
AB  - PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor
      effects resulting from the direct lysis of cancer cells. HSVs may also be used to
      express inserted transgenes to exploit additional therapeutic strategies. The
      ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma
      (SCC) by inhibition of tumor angiogenesis is investigated in this study.
      EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying
      the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or
      saline was used to treat established murine SCC flank tumors by intratumoral
      injection. The expression of secondary antiangiogenic mediators was measured.
      Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor
      subdermal vascularity, and in vitro endothelial cell tubule formation assay.
      RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into
      murine SCC VII flank tumors resulted in smaller tumor volumes as compared with
      NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg,
      respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were
      undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two
      antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible
      protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042
      transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin
      content and microvessel density as compared with NV1023 and PBS. Excised murine
      flank tumors treated with NV1042 had decreased subdermal vascularity as compared
      with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were
      required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL
      12 expression by an oncolytic herpes virus enhances therapy of SCC through
      antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis
      inhibition merit further investigation for potential clinical application.

PMID- 15240544
TI  - Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by
      reducing matrix metalloproteinases and angiogenesis.
AB  - Gabexate mesilate (GM), a synthetic protease inhibitor, has an antiproteinase
      activity on various types of plasma serine proteases. However, its role on matrix
      metalloproteinases (MMPs) has not been identified. In this study, we investigated
      the effect of GM on MMPs and on the invasion and metastasis of human colon cancer
      cell lines and neoangiogenesis. The activities of MMPs secreted from these cells
      were significantly reduced by GM but unaffected by the serine protease inhibitor
      aprotinin. GM directly inhibited purified progelatinase A derived from T98G human
      glioblastoma cells. In vitro, GM significantly reduced the invasive ability of
      colon cancer cells but not cellular motility, whereas aprotinin affected neither.
      Liver metastatic ability and tumorigenic potential in nude mice were remarkably
      reduced on treatment with GM. Immunohistochemical analysis of GM-treated tumors
      in mice showed a marked increase in apoptosis and a significant reduction in
      tumor angiogenesis. Human umbilical vein endothelial cell proliferation, tube
      formation, and neoangiogenesis in the rabbit cornea and Matrigel implanted in
      mice were significantly inhibited by GM. These results suggest that GM is a novel
      inhibitor of MMPs and that it may inhibit the invasion and metastasis of human
      colon cancer cells by blocking MMPs and neoangiogenesis.

PMID- 15240545
TI  - Combinatorial administration of molecules that simultaneously inhibit
      angiogenesis and invasion leads to increased therapeutic efficacy in mouse models
      of malignant glioma.
AB  - PURPOSE: We investigated the ability of the combinatorial administration of
      different inhibitors with activities on glioma angiogenesis, migration, and
      proliferation to produce a prolonged inhibition of glioma growth. EXPERIMENTAL
      DESIGN: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF,
      cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX,
      PF-4/DLR). RESULTS: When administered in combination, these drugs produced a
      prolonged and increased inhibition of glioma growth independently from the type
      of inhibitor used. The combinatory administration was more effective than the
      administration of a single inhibitor alone, and a strong therapeutic response was
      reached with a significantly lower amount of protein. The strongest inhibition
      was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis
      and invasion by separate mechanisms, were combined. CONCLUSIONS: This supports
      the concept that prolonged glioma growth inhibition can be achieved by
      simultaneous delivery of molecules that target both tumor and endothelial cells
      and acting by separate mechanisms.

PMID- 15240546
TI  - Antibody-targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl
      gamma calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy
      positive human carcinoma cells and xenografts.
AB  - PURPOSE: Linking a cytotoxic anticancer drug to an antibody that recognizes a
      tumor-associated antigen can improve the therapeutic index of the drug. We asked
      whether a conjugate of the cytotoxic antibiotic N-acetyl gamma calicheamicin
      dimethyl hydrazide (CalichDMH) and an antibody recognizing Lewis(y) (Le(y))
      antigen could eliminate carcinomas that express Le(y). Because Le(y) is highly
      expressed on carcinomas of colon, breast, lung, ovary, and prostate, a CalichDMH
      conjugate targeting Le(y) could provide a treatment option for various cancers.
      EXPERIMENTAL DESIGN: The humanized anti-Le(y) antibody hu3S193 was conjugated to
      CalichDMH via the bifunctional AcBut linker. Selectivity and avidity of the
      conjugate (hu3S193-CalichDMH) for Le(y)-BSA or Le(y+) cells was tested by BIAcore
      or flow cytometry. Cytotoxicity of hu3S193-CalichDMH was compared with toxicity
      of a control conjugate on monolayers of Le(y+) and Le(y-) carcinoma cells.
      Inhibition of tumor growth by hu3S193-CalichDMH was assessed on three types of
      s.c. xenografts. RESULTS: Hu3S193-CalichDMH had similar selectivity as hu3S193.
      The conjugate had lower affinity for Le(y)-BSA but not for Le(y+) cells. When
      tested on monolayers of human Le(y+) carcinoma cells, hu3S193-CalichDMH was more
      cytotoxic than a control conjugate. This difference in efficacy was not noted on
      Le(y-) cells. Efficacy of hu3S193-CalichDMH depended on the expression of Le(y)
      and on the sensitivity of the cells to CalichDMH. In vivo, hu3S193-CalichDMH
      inhibited growth of xenografted human gastric (N87), colon (LOVO), and prostate
      carcinomas (LNCaP). When used against N87 xenografts, hu3S193-CalichDMH arrested
      tumor growth for at least 100 days. CONCLUSION: Hu3S193-CalichDMH can
      specifically eliminate Le(y+) tumors. These results support development of this
      conjugate for treatment of carcinomas.

PMID- 15240547
TI  - Treatment of pancreatic cancer cells with dicumarol induces cytotoxicity and
      oxidative stress.
AB  - PURPOSE:  NAD(P)H: quinone oxidoreductase (NQO(1)) catalyzes the two-electron
      reduction of quinones to hydroquinones. This reaction is believed to prevent the
      one-electron reduction of quinones that would result in redox cycling with
      generation of superoxide (O(2)(.-)). We have recently demonstrated that
      inhibition of NQO(1) with dicumarol increases intracellular O(2)(.-) production
      and inhibits the in vitro malignant phenotype of pancreatic cancer cells (J.
      Cullen et al., Cancer Res., 63: 5513-5520, 2003). We hypothesized that inhibition
      of NQO(1) would increase cell killing, induce oxidative stress, and inhibit in
      vivo tumor growth. EXPERIMENTAL DESIGN AND RESULTS: In the human pancreatic
      cancer cell line MIA PaCa-2, dicumarol decreased cell viability, as measured by
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and
      decreased clonogenic survival. Dicumarol increased the percentage of apoptotic
      cells in a time-dependent and dose-dependent manner as measured by 3,3'
      diaminobenzidine staining and flow cytometry, which was associated with
      cytochrome c release and poly(ADP-ribose) polymerase cleavage. Dicumarol also
      induced oxidative stress as evidenced by increased total glutathione and oxidized
      glutathione, as well as sensitizing to cell killing mediated by menadione. In
      established orthotopic pancreatic tumors in nude mice, intratumoral injections of
      dicumarol slowed tumor growth and extended survival. CONCLUSIONS: Inhibition of
      NQO(1) with dicumarol induces cell killing and oxidative stress in pancreatic
      cancer cells and speculate that dicumarol may prove to be useful in pancreatic
      cancer therapeutics.

PMID- 15240548
TI  - Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer
      model.
AB  - PURPOSE: It is established that bisphosphonates (BPs), specific inhibitors of
      osteoclasts, have beneficial effects on bone metastases of breast cancer. In
      addition, recent studies have reported that BPs have anticancer effects and
      suppress visceral metastases, too. However, the results of clinical studies are
      still conflicting. In the present study, we examined the effects of the BP
      zoledronic acid (ZOL), one of the most potent BPs currently available, on
      visceral metastases of breast cancer using an animal model in which mouse breast
      cancer cells 4T1/luc implanted at the orthotopic mammary fat pad spontaneously
      metastasize to multiple organs including bone, lung, and liver in female BALB/c
      mice. EXPERIMENTAL DESIGN AND RESULTS: The 4T1/luc-bearing mice received single
      or four i.v. injections of ZOL (0.5 or 5 microg/mouse) during the whole
      experimental period. Bone metastases were reduced by the ZOL treatment. More
      importantly, ZOL significantly suppressed lung and liver metastases. Furthermore,
      ZOL prolonged overall survival of the tumor-bearing mice. Of interest, apoptosis
      in 4T1/luc cells colonized in bone was increased by ZOL; however, those in lung
      were not changed. In vitro studies demonstrated that ZOL inhibited cell migration
      and invasion and promoted apoptosis of 4T1/luc cells. CONCLUSIONS: These results
      are consistent with the notion that ZOL affects breast cancer metastasis to
      visceral organs as well as bone. These effects of ZOL may be attributable to
      inhibition of migration and invasion of breast cancer cells. Clinical relevance
      of our experimental results needs to be determined in breast cancer patients with
      visceral metastases.

PMID- 15240549
TI  - Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene
      induction of mammary cancer: blockade at the initial phase of carcinogenesis.
AB  - PURPOSE: There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA),
      type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit
      but contain distinct regulatory (R) subunits, RI versus RII, respectively.
      Evidence suggests that increased expression of PKA-I and its regulatory subunit
      (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the
      effect of sequence-specific inhibition of RIalpha gene expression at the initial
      phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary
      carcinogenesis. EXPERIMENTAL DESIGN: Antisense RIalpha oligodeoxynucleotide (ODN)
      targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before
      DMBA intubation and during the first 9 days post-DMBA intubation to determine the
      anticarcinogenic effects. RESULTS: Antisense RIalpha, in a sequence-specific
      manner, inhibited the tumor production. At 90 days after DMBA intubation,
      untreated controls and RIalpha-antisense-treated rats exhibited an average mean
      number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45%
      of antisense-treated animals had tumors. The antisense also delayed the first
      tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland
      and liver preceded DMBA-induced tumor production, and antisense down-regulation
      of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense
      RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and
      quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP
      response element (CRE)-directed transcription. In the mammary glands, antisense
      RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor
      decoy could not mimic these effects of antisense RIalpha. CONCLUSIONS: The
      results demonstrate that RIalpha antisense produces dual anticarcinogenic
      effects: (a) increasing DMBA detoxification in the liver by increasing phase II
      enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing
      CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in
      the mammary gland by down-regulating PKA-I.

PMID- 15240550
TI  - Confocal microscopic analysis of the interaction between cisplatin and the copper
      transporter ATP7B in human ovarian carcinoma cells.
AB  - Some cisplatin (DDP)-resistant cells overexpress the copper export transporter
      ATP7B, and cells molecularly engineered to overexpress ATP7B are resistant to
      DDP. The interaction of Cu with ATP7B normally triggers its relocalization from
      the perinuclear region to more peripheral vesicles. To investigate the
      interaction of DDP with ATP7B, we examined the effect of DDP on the subcellular
      localization of ATP7B using human ovarian carcinoma cells expressing a cyan
      fluorescent protein (ECFP)-tagged ATP7B (2008/ECFP-ATP7B). ATP7B expression was
      confirmed in 2008/ECFP-ATP7B cells by Western blotting, and its functionality was
      documented by showing that it rendered the cells 1.9-fold resistant to CuSO(4)
      and 4.1-fold resistant to DDP and also reduced the accumulation of both drugs.
      There was greater sequestration of Pt into intracellular vesicles in the
      2008/ECFP-ATP7B cells than in the 2008/ECFP cells. Confocal digital microscopy
      revealed that ECFP-ATP7B localized in the perinuclear region in absence of drug
      exposure and that both Cu and DDP triggered relocalization to more peripheral
      vesicular structures. A fluorescein-labeled form of DDP that retained
      cytotoxicity and was subject to the same mechanisms of resistance as DDP
      colocalized with ECFP-ATP7B in the 2008/ECFP-ATP7B cells, whereas the same
      fluorochrome lacking the DDP moiety did not. These results provide evidence that
      DDP directly interacts with ATP7B to trigger its relocalization and that ATP7B
      mediates resistance to DDP by sequestering it into vesicles of the secretory
      pathway for export from the cell.

PMID- 15240551
TI  - Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult
      mouse brain.
AB  - In many species, the Sox2 transcription factor is a marker of the nervous system
      from the beginning of its development, and we have previously shown that Sox2 is
      expressed in embryonic neural stem cells. It is also expressed in, and is
      essential for, totipotent inner cell mass stem cells and other multipotent cell
      lineages, and its ablation causes early embryonic lethality. To investigate the
      role of Sox2 in the nervous system, we generated different mouse mutant alleles:
      a null allele (Sox2beta-geo 'knock-in'), and a regulatory mutant allele
      (Sox2DeltaENH), in which a neural cell-specific enhancer is deleted. Sox2 is
      expressed in embryonic early neural precursors of the ventricular zone and, in
      the adult, in ependyma (a descendant of the ventricular zone). It is also
      expressed in the vast majority of dividing precursors in the neurogenic regions,
      and in a small proportion of differentiated neurones, particularly in the
      thalamus, striatum and septum. Compound Sox2(beta-geo/DeltaENH) heterozygotes
      show important cerebral malformations, with parenchymal loss and ventricle
      enlargement, and L-dopa-rescuable circling behaviour and epilepsy. We observed
      striking abnormalities in neurones; degeneration and cytoplasmic protein
      aggregates, a feature common to diverse human neurodegenerative diseases, are
      observed in thalamus, striatum and septum. Furthermore, ependymal cells show
      ciliary loss and pathological lipid inclusions. Finally, precursor cell
      proliferation and the generation of new neurones in adult neurogenic regions are
      greatly decreased, and GFAP/nestin-positive hippocampal cells, which include the
      earliest neurogenic precursors, are strikingly diminished. These findings
      highlight a crucial and unexpected role for Sox2 in the maintenance of neurones
      in selected brain areas, and suggest a contribution of neural cell proliferative
      defects to the pathological phenotype.

PMID- 15240552
TI  - KNUCKLES (KNU) encodes a C2H2 zinc-finger protein that regulates development of
      basal pattern elements of the Arabidopsis gynoecium.
AB  - Flowers of the parthenocarpic knuckles mutant are conditionally male sterile and
      contain ectopic stamens and carpels that originate from placental tissue within
      developing gynoecia. The mutation was mapped to a 123 Kb interval on chromosome 5
      using molecular markers. All aspects of the knuckles phenotype could be
      complemented by a genomic fragment from the region which contained the annotated
      MAC12.2 gene. A guanine to adenine transition within a predicted C2H2 zinc finger
      encoding region of MAC12.2 causes the second of two critical zinc-binding
      cysteine residues to be replaced by a tyrosine. Transgenic plants in which
      translational fusions of the GUS reporter to KNUCKLES were driven by the
      presumptive KNUCKLES promoter indicate that the gene is expressed first in
      developing carpel primordia, and later in stamens and ovules of flower buds. In
      situ hybridization experiments showed a broader pattern of transcript
      localization, suggesting that post-transcriptional regulatory mechanisms may
      limit KNUCKLES protein accumulation and localization. Based on genetic evidence
      and the presence of a carboxy-terminal motif demonstrated by others to function
      as an active repression domain, we propose that KNUCKLES might function as a
      transcriptional repressor of cellular proliferation that regulates floral
      determinacy and relative size of basal pattern elements along the proximo-distal
      axis of the developing Arabidopsis gynoecium.

PMID- 15240553
TI  - Combinatorial gene regulation by Bmp and Wnt in zebrafish posterior mesoderm
      formation.
AB  - Combinatorial signaling is an important mechanism that allows the embryo to
      utilize overlapping signaling pathways to specify different territories. In
      zebrafish, the Wnt and Bmp pathways interact to regulate the formation of the
      posterior body. In order to understand how this works mechanistically, we have
      identified tbx6 as a posterior mesodermal gene activated by both of these
      signaling pathways. We isolated a genomic fragment from the tbx6 gene that
      recapitulates the endogenous tbx6 expression, and used this to ask how the Bmp
      and Wnt signaling pathways combine to regulate gene expression. We find that the
      tbx6 promoter utilizes distinct domains to integrate the signaling inputs from
      each pathway, including multiple Tcf/LEF sites and a novel Bmp-response element.
      Surprisingly, we found that overexpression of either signaling pathway can
      activate the tbx6 promoter and the endogenous gene, whereas inputs from both
      pathways are required for the normal pattern of expression. These results
      demonstrate that both Bmp and Wnt are present at submaximal levels, which allows
      the pathways to function combinatorially. We present a model in which overlapping
      Wnt and Bmp signals in the ventrolateral region activate the expression of tbx6
      and other posterior mesodermal genes, leading to the formation of posterior
      structures.

PMID- 15240554
TI  - Selective loss of imprinting in the placenta following preimplantation
      development in culture.
AB  - Preimplantation development is a period of dynamic epigenetic change that begins
      with remodeling of egg and sperm genomes, and ends with implantation. During this
      time, parental-specific imprinting marks are maintained to direct appropriate
      imprinted gene expression. We previously demonstrated that H19 imprinting could
      be lost during preimplantation development under certain culture conditions. To
      define the lability of genomic imprints during this dynamic period and to
      determine whether loss of imprinting continues at later stages of development,
      imprinted gene expression and methylation were examined after in vitro
      preimplantation culture. Following culture in Whitten's medium, the normally
      silent paternal H19 allele was aberrantly expressed and undermethylated. However,
      only a subset of individual cultured blastocysts (approximately 65%) exhibited
      biallelic expression, while others maintained imprinted H19 expression. Loss of
      H19 imprinting persisted in mid-gestation conceptuses. Placental tissues
      displayed activation of the normally silent allele for H19, Ascl2, Snrpn, Peg3
      and Xist while in the embryo proper imprinted expression for the most part was
      preserved. Loss of imprinted expression was associated with a decrease in
      methylation at the H19 and Snrpn imprinting control regions. These results
      indicate that tissues of trophectoderm origin are unable to restore genomic
      imprints and suggest that mechanisms that safeguard imprinting might be more
      robust in the embryo than in the placenta.

PMID- 15240555
TI  - The winged helix transcription factor Foxg1 facilitates retinal ganglion cell
      axon crossing of the ventral midline in the mouse.
AB  - During normal development, retinal ganglion cells (RGCs) project axons along the
      optic nerve to the optic chiasm on the ventral surface of the hypothalamus. In
      rodents, most RGC growth cones then cross the ventral midline to join the
      contralateral optic tract; those that do not cross join the ipsilateral optic
      tract. Contralaterally projecting RGCs are distributed across the retina whereas
      ipsilaterally projecting RGCs are concentrated in temporal retina. The
      transcription factor Foxg1 (also known as BF1) is expressed at several key
      locations along this pathway. Analysis of Foxg1 expression using lacZ reporter
      transgenes shows that Foxg1 is normally expressed in most, if not all, nasal RGCs
      but not in most temporal RGCs, neither at the time they project nor earlier in
      their lineage. Foxg1 is also expressed at the optic chiasm. Mice that lack Foxg1
      die at birth and, although the shape of their eyes is abnormal, their retinas
      still project axons to the brain via the optic chiasm. Using anterograde and
      retrograde tract tracing, we show that there is an eightfold increase in the
      ipsilateral projection in Foxg1-/- embryos. The distributions of cells expressing
      the transcription factors Foxg1 and Nkx2.2, and cell-surface molecules Ephb2,
      ephrin B2 and SSEA-1 (Fut4) have been correlated to the normally developing
      retinothalamic projection and we show they are not much altered in the developing
      Foxg1-/- retina and optic chiasm. As much of the increased ipsilateral projection
      in Foxg1-/- embryos arises from temporal RGCs that are unlikely to have an
      autonomous requirement for Foxg1, we propose that the phenotype reflects at least
      in part a requirement for Foxg1 outwith the RGCs themselves, most likely at the
      optic chiasm.

PMID- 15240556
TI  - Interactions between Fat and Dachsous and the regulation of planar cell polarity
      in the Drosophila wing.
AB  - It was recently suggested that a proximal to distal gradient of the protocadherin
      Dachsous (Ds) acts as a cue for planar cell polarity (PCP) in the Drosophila
      wing, orienting cell-cell interactions by inhibiting the activity of the
      protocadherin Fat (Ft). This Ft-Ds signaling model is based on mutant loss-of
      function phenotypes, leaving open the question of whether Ds is instructive or
      permissive for PCP. We developed tools for misexpressing ds and ft in vitro and
      in vivo, and have used these to test aspects of the model. First, this model
      predicts that Ds and Ft can bind. We show that Ft and Ds mediate preferentially
      heterophilic cell adhesion in vitro, and that each stabilizes the other on the
      cell surface. Second, the model predicts that artificial gradients of Ds are
      sufficient to reorient PCP in the wing; our data confirms this prediction.
      Finally, loss-of-function phenotypes suggest that the gradient of ds expression
      is necessary for correct PCP throughout the wing. Surprisingly, this is not the
      case. Uniform levels of ds drive normally oriented PCP and, in all but the most
      proximal regions of the wing, uniform ds rescues the ds mutant PCP phenotype. Nor
      are distal PCP defects increased by the loss of spatial information from the
      distally expressed four-jointed (fj) gene, which encodes putative modulator of Ft
      Ds signaling. Thus, while our results support the existence of Ft-Ds binding and
      show that it is sufficient to alter PCP, ds expression is permissive or redundant
      with other PCP cues in much of the wing.

PMID- 15240557
TI  - SOX9 specifies the pyloric sphincter epithelium through mesenchymal-epithelial
      signals.
AB  - Gastrointestinal (GI) development is highly conserved across vertebrates.
      Although several transcription factors and morphogenic proteins are involved in
      the molecular controls of GI development, the interplay between these factors is
      not fully understood. We report herein the expression pattern of Sox9 during GI
      development, and provide evidence that it functions, in part, to define the
      pyloric sphincter epithelium. SOX9 is expressed in the endoderm of the GI tract
      (with the exclusion of the gizzard) and its derivate organs, the lung and
      pancreas. Moreover, SOX9 is also expressed at the mesoderm of the pyloric
      sphincter, a structure that demarcates the gizzard from the duodenum. Using
      retroviral misexpression technique, we show that Sox9 expression in the pyloric
      sphincter is under the control of the BMP signaling pathway, known to play a key
      role in the development of this structure. By misexpressing SOX9 in the mesoderm
      of the gizzard, we show that SOX9 is able to transdifferentiate the adjacent
      gizzard epithelium into pyloric sphincter-like epithelium through the control of
      mesodermal-epithelial signals mediated in part by Gremlin (a modulator of the BMP
      pathway). Our results suggest that SOX9 is necessary and sufficient to specify
      the pyloric sphincter epithelial properties.

PMID- 15240558
TI  - Trypanosome trans-sialidase targets TrkA tyrosine kinase receptor and induces
      receptor internalization and activation.
AB  - Trypanosome trans-sialidase (TS) is a sialic acid-transferring enzyme that
      hydrolyzes alpha2,3-linked sialic acids and transfers them to acceptor molecules.
      Here we show that a highly purified recombinant TS derived from T. cruzi
      parasites targets TrkA receptors on TrkA-expressing PC12 cells and colocalizes
      with TrkA internalization and phosphorylation (pTrkA). Maackia amurensis lectin
      II (MAL-II) and Sambucus nigra lectin (SNA) block TS binding to TrkA-PC12 cells
      in a dose-dependent manner with subsequent inhibition of TS colocalization with
      pTrkA. Cells treated with lectins alone do not express pTrkA. The catalytically
      inactive mutant TSDeltaAsp98-Glu also binds to TrkA-expressing cells, but is
      unable to induce pTrkA. TrkA-PC12 cells treated with a purified recombinant
      alpha2,3-neuraminidase (Streptococcus pneumoniae) express pTrkA. Wild-type TS but
      not the mutant TSDeltaAsp98-Glu promotes neurite outgrowth in TrkA-expressing
      PC12 cells. In contrast, these effects are not observed in TrkA deficient
      PC12nnr5 cells but are reestablished in PC12nnr5 cells stably transfected with
      TrkA and are significantly blocked by inhibitors of tyrosine kinase (K-252a) and
      MAP/MEK protein kinase (PD98059). Together these observations suggest for the
      first time that hydrolysis of sialyl alpha2,3-linked beta-galactosyl residues of
      TrkA receptors plays an important role in TrkA receptor activation, sufficient to
      promote cell differentiation (neurite outgrowth) independent of nerve growth
      factor.

PMID- 15240561
TI  - Cell surface sialic acids do not affect primary CD22 interactions with CD45 and
      surface IgM nor the rate of constitutive CD22 endocytosis.
AB  - CD22/Siglec-2 is a B cell-specific molecule modulating surface IgM (sIgM)
      signaling via cytosolic tyrosine-based motifs. CD22 recognizes alpha2-6-linked
      sialic acids (Sias) via an amino-terminal Ig-like domain. This Sia-binding site
      is typically masked by unknown sialylated ligands on the same cell surface, an
      interaction required for optimal signaling function. We studied the effect of
      cell surface Sias on specific interactions of CD22 with other molecules and on
      its turnover via endocytosis. A novel approach for simultaneous biotinylation and
      cross-linking showed that CD22 associates with CD45 and sIgM at much higher
      levels than reported in prior studies, possibly involving cell surface multimers
      of CD22. Sia removal or mutation of a CD22 arginine residue required for Sia
      recognition did not affect these associations even in human:mouse heterologous
      systems, indicating that they are primarily determined by evolutionarily
      conserved protein-protein interactions. Thus masking of the Sia-binding site of
      CD22 involves many cell surface sialoglycoproteins, without requiring specific
      ligand(s) and/or is mediated by secondary interactions with Sias on CD45 and
      sIgM. Abrogating Sia interactions also does not affect constitutive CD22
      endocytosis. Sia removal does enhance the much faster rate of anti-CD22 antibody
      triggered endocytosis, as well as killing by an anti-CD22 immunotoxin. In
      contrast to the unstimulated state, sIgM cross-linking inhibits both antibody
      induced endocytosis and immunotoxin killing. Thus the signal- modulating activity
      of CD22 Sia recognition cannot be explained by mediation of primary interactions
      with specific molecules, nor by effects on constitutive endocytosis. The effects
      on antibody-mediated endocytosis could be of relevance to immunotoxin treatment
      of lymphomas.

PMID- 15240562
TI  - HIV-1 Nef equips dendritic cells to reduce survival and function of CD8+ T cells:
      a mechanism of immune evasion.
AB  - The accessory HIV-1 Nef protein is a crucial determinant for viral replication
      and pathogenesis. During HIV infection, loss of immune control in the setting of
      a strong and broad HIV-specific T-lymphocyte response, leads to a lethal outcome
      through AIDS. Moreover, dysfunction of dendritic cells (DCs) may contribute to
      the immune suppression associated with AIDS progression. We recently demonstrated
      that exogenous Nef selectively activates immature DCs manipulating their
      phenotypical, morphological, and functional developmental program. Here, we
      tracked whether Nef, targeting DCs, could be involved in the dysregulation of
      CD8+ T cell responses. We found that Nef inhibits the capacity of DCs to prime
      alloreactive CD8+ T cell responses down-regulating their proliferation and
      functional competence. This coincides with the induction of CD8+ T cell
      apoptosis. Nef oversees apoptotic killing of CD8+ T cells up-regulating TNF-alpha
      and FasL production by DCs and interfering with the death receptor pathway in
      CD8+ T cells and thus activating caspase 8. Our findings suggest that Nef may
      contribute to the immune evasion associated with HIV-1 infection, subverting DC
      biology. This may help explain the pleiotropic function that Nef plays during
      infection and makes this protein an attractive target for preventive and
      therapeutic intervention.

PMID- 15240563
TI  - Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and
      HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF
      2alpha target gene in Hep3B and Kelly cells.
AB  - Activation of the hypoxia-inducible factor alpha-subunits, HIF-1alpha and HIF
      2alpha, seems to be subject to similar regulatory mechanisms, and transgene
      approaches suggested partial functional redundancy. Here, we used RNA
      interference to determine the contribution of HIF-1alpha vs. HIF-2alpha to the
      hypoxic gene induction. Surprisingly, most genes tested were responsive only to
      the HIF-1alpha siRNA, showing no effect by HIF-2alpha knock-down. The same was
      found for the activation of reporter genes driven by hypoxia-responsive elements
      (HREs) from the erythropoietin (EPO), vascular endothelial growth factor, or
      phosphoglycerate kinase gene. Interestingly, EPO was the only gene investigated
      that showed responsiveness only to HIF-2alpha knock-down, as observed in Hep3B
      and Kelly cells. In contrast to the EPO-HRE reporter, the complete EPO enhancer
      displayed dependency on HIF-2alpha regulation, indicating that additional cis
      acting elements confer HIF-2alpha specificity within this region. In 786-0 cells
      lacking HIF-1alpha protein, the identified HIF-1alpha target genes were regulated
      by HIF-2alpha. Overexpression of the HIFalpha subunits in different cell lines
      also led to a loss of target gene specificity. In conclusion, we found a
      remarkably restricted target gene specificity of the HIFalpha subunits, which can
      be overcome in cells with perturbations in the pVHL/HIF system and under forced
      expression.

PMID- 15240564
TI  - Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death
      via activation of calpains.
AB  - Chondrocyte cell death is a hallmark of inflammatory and degenerative joint
      diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA), but the
      molecular and cellular mechanisms involved have yet to be elucidated. Because 3
      nitrotyrosine, a marker for reactive nitrogen species such as peroxynitrite, has
      been observed in OA and RA cartilage and has been associated with chondrocyte
      cell death, we investigated the mechanisms by which peroxynitrite induces cell
      death in human articular chondrocytes. The earliest biochemical event observed,
      subsequent to treatment with either peroxynitrite or the peroxynitrite generator
      SIN-1, was a rapid rise in intracellular calcium that lead to mitochondrial
      dysfunction and cell death. Although, chondrocyte death exhibited several
      classical hallmarks of apoptosis, including annexin V labeling, increased
      fraction of cells with subG1 DNA content and DNA condensation, we did not find
      evidence for caspase involvement either by Western blotting, fluorimetric assays,
      or caspase inhibition. Additionally, peroxynitrite did not inhibit cellular
      caspase activity. Furthermore, using other established assays of cell viability,
      including the MTT assay and release of lactate dehydrogenase, we found that the
      predominant mode of cell death involved calcium-dependent cysteine proteases,
      otherwise known as calpains. Our data show, for the first time, that
      peroxynitrite induces mitochondrial dysfunction in cells via a calcium-dependent
      process that leads to caspase-independent apoptosis mediated by calpains.

PMID- 15240565
TI  - ORP150/HSP12A protects renal tubular epithelium from ischemia-induced cell death.
AB  - The 150 kDa oxygen-regulated protein (ORP150) is an inducible endoplasmic
      reticulum (ER) chaperone with cytoprotective properties in settings of cell
      stress, such as ischemia/reperfusion (I/R). Renal tissue from patients with acute
      renal failure displayed strong induction of ORP150 in tubular epithelium. In a
      rodent model of renal I/R injury, ORP150 was expressed in both the ischemic and
      contralateral kidney, principally in the thick ascending loop of Henle (TAL) and
      distal tubules. Cultured renal epithelial cells exposed to hypoxic or
      hyperosmotic conditions displayed induction of ORP150. Renal tubular epithelial
      cells stably transfected with ORP150 sense or antisense cDNA displayed a strong
      correlation between ORP150 expression and vulnerability to hypoxic/osmotic
      stress; higher levels of ORP150 were protective, whereas lower levels increased
      susceptibility to cell death. Compared with nontransgenic controls, transgenic
      mice overexpressing ORP150 subjected to renal I/R displayed a blunted rise of
      serum creatinine and blood urea nitrogen, and enhanced survival of TAL,
      consistent with cytoprotection. In contrast, heterozygous ORP150+/- mice, with
      lower levels of ORP150, showed enhanced renal injury. These data are consistent
      with the possibility that ORP150 exerts cytoprotective effects in renal tubular
      epithelia subjected to I/R injury and suggest a key role for ER stress in the
      renal tubular response to acute renal failure.

PMID- 15240566
TI  - What's in a picture? The temptation of image manipulation.

PMID- 15240567
TI  - Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction
      of neurites.
AB  - Extension of neurites requires the SNARE-dependent fusion of plasmalemmal
      precursor vesicles with the plasma membrane of growth cones. Here, we show that
      tomosyn localizes at the palm of growth cones and inhibits the fusion of the
      vesicles there, thus promoting transport of the vesicles to the plasma membrane
      of the leading edges of growth cones. Tomosyn localizes because ROCK activated by
      Rho small G protein phosphorylates syntaxin-1, which increases the affinity of
      syntaxin-1 for tomosyn and forms a stable complex with tomosyn, resulting in
      inhibition of the formation of the SNARE complex. In retraction of neurites,
      tomosyn localizes all over the edges of the neurites and inhibits fusion of the
      vesicles with the plasma membrane. Thus, tomosyn demarcates the plasma membrane
      by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension
      and retraction of neurites.

PMID- 15240568
TI  - SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway,
      and represses the CDX2 and MUC2 genes.
AB  - TCF and SOX proteins belong to the high mobility group box transcription factor
      family. Whereas TCFs, the transcriptional effectors of the Wnt pathway, have been
      widely implicated in the development, homeostasis and disease of the intestine
      epithelium, little is known about the function of the SOX proteins in this
      tissue. Here, we identified SOX9 in a SOX expression screening in the mouse fetal
      intestine. We report that the SOX9 protein is expressed in the intestinal
      epithelium in a pattern characteristic of Wnt targets. We provide in vitro and in
      vivo evidence that a bipartite beta-catenin/TCF4 transcription factor, the
      effector of the Wnt signaling pathway, is required for SOX9 expression in
      epithelial cells. Finally, in colon epithelium-derived cells, SOX9
      transcriptionally represses the CDX2 and MUC2 genes, normally expressed in the
      mature villus cells of the intestinal epithelium, and may therefore contribute to
      the Wnt-dependent maintenance of a progenitor cell phenotype.

PMID- 15240569
TI  - Mutations in orbit/mast reveal that the central spindle is comprised of two
      microtubule populations, those that initiate cleavage and those that propagate
      furrow ingression.
AB  - We address the relative roles of astral and central spindle microtubules (MTs) in
      cytokinesis of Drosophila melanogaster primary spermatocytes. Time-lapse imaging
      studies reveal that the central spindle is comprised of two MT populations,
      "interior" central spindle MTs found within the spindle envelope and "peripheral"
      astral MTs that probe the cytoplasm and initiate cleavage furrows where they
      contact the cortex and form overlapping bundles. The MT-associated protein
      Orbit/Mast/CLASP concentrates on interior rather than peripheral central spindle
      MTs. Interior MTs are preferentially affected in hypomorphic orbit mutants, and
      consequently the interior central spindle fails to form or is unstable. In
      contrast, peripheral MTs still probe the cortex and form regions of overlap that
      recruit the Pav-KLP motor and Aurora B kinase. orbit mutants have disorganized or
      incomplete anillin and actin rings, and although cleavage furrows initiate, they
      ultimately regress. Our work identifies a new function for Orbit/Mast/CLASP and
      identifies a novel MT population involved in cleavage furrow initiation.

PMID- 15240570
TI  - Mutations in sticky lead to defective organization of the contractile ring during
      cytokinesis and are enhanced by Rho and suppressed by Rac.
AB  - The contractile ring is a highly dynamic structure, but how this dynamism is
      accomplished remains unclear. Here, we report the identification and analysis of
      a novel Drosophila gene, sticky (sti), essential for cytokinesis in all fly
      proliferating tissues. sti encodes the Drosophila orthologue of the mammalian
      Citron kinase. RNA interference-mediated silencing of sti in cultured cells
      causes them to become multinucleate. Components of the contractile ring and
      central spindle are recruited normally in such STICKY-depleted cells that
      nevertheless display asymmetric furrowing and aberrant blebbing. Together with an
      unusual distribution of F-actin and Anillin, these phenotypes are consistent with
      defective organization of the contractile ring. sti shows opposite genetic
      interactions with Rho and Rac genes suggesting that these GTPases
      antagonistically regulate STICKY functions. Similar genetic evidence indicates
      that RacGAP50C inhibits Rac during cytokinesis. We discuss that antagonism
      between Rho and Rac pathways may control contractile ring dynamics during
      cytokinesis.

PMID- 15240571
TI  - Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated
      Notch receptor.
AB  - Activation of mammalian Notch receptor by its ligands induces TNFalpha-converting
      enzyme-dependent ectodomain shedding, followed by intramembrane proteolysis due
      to presenilin (PS)-dependent gamma-secretase activity. Here, we demonstrate that
      a new modification, a monoubiquitination, as well as clathrin-dependent
      endocytosis, is required for gamma-secretase processing of a constitutively
      active Notch derivative, DeltaE, which mimics the TNFalpha-converting enzyme
      processing product. PS interacts with this modified form of DeltaE, DeltaEu. We
      identified the lysine residue targeted by the monoubiquitination event and
      confirmed its importance for activation of Notch receptor by its ligand, Delta
      like 1. We propose a new model where monoubiquitination and endocytosis of Notch
      are a prerequisite for its PS-dependent cleavage, and discuss its relevance for
      other gamma-secretase substrates.

PMID- 15240574
TI  - Clinical review 168: What vascular ultrasound testing has revealed about
      pediatric atherogenesis, and a potential clinical role for ultrasound in
      pediatric risk assessment.
AB  - Coronary vascular disease is one facet of a generalized disturbance of vascular
      function present throughout the vascular tree. Dysfunction of the endothelium
      leads to thickening of the intima and media of the vessel wall of large and
      medium-sized muscular arteries and large elastic arteries, such as the aorta,
      carotid, and iliac arteries. Flow-mediated dilatation of the brachial artery is
      one of several tests used to assess dysfunction of the endothelium using high
      resolution ultrasound. Endothelial dysfunction has been demonstrated in children
      with heterozygous familial hypercholesterolemia, type 1 diabetes, morbid obesity,
      and homozygous homocystinuria and in the offspring of a parent with early
      coronary disease. High resolution ultrasound has also confirmed postmortem
      findings that atherogenesis has its beginnings in childhood and adolescence, with
      the demonstration of increased carotid artery intima-medial thickening in
      children with familial hypercholesterolemia, familial combined hyperlipidemia,
      and type 1 diabetes and in the offspring of a parent with early coronary disease.
      In combination with family history and traditional risk factors, ultrasound
      evaluation of brachial artery flow-mediated vasodilation and carotid artery
      intima-medial thickening could be used in a clinical setting to assess coronary
      risk in high risk pediatric patients.

PMID- 15240572
TI  - Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal
      adhesions through alpha2beta1 integrin.
AB  - Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan
      perlecan, inhibits several aspects of angiogenesis. We provide evidence for a
      novel biological axis that links a soluble fragment of perlecan protein core to
      the major cell surface receptor for collagen I, alpha2beta1 integrin, and provide
      an initial investigation of the intracellular signaling events that lead to
      endorepellin antiangiogenic activity. The interaction between endorepellin and
      alpha2beta1 integrin triggers a unique signaling pathway that causes an increase
      in the second messenger cAMP; activation of two proximal kinases, protein kinase
      A and focal adhesion kinase; transient activation of p38 mitogen-activated
      protein kinase and heat shock protein 27, followed by a rapid down-regulation of
      the latter two proteins; and ultimately disassembly of actin stress fibers and
      focal adhesions. The end result is a profound block of endothelial cell migration
      and angiogenesis. Because perlecan is present in both endothelial and smooth
      muscle cell basement membranes, proteolytic activity during the initial stages of
      angiogenesis could liberate antiangiogenic fragments from blood vessels' walls,
      including endorepellin.

PMID- 15240573
TI  - Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline
      secretion.
AB  - It is generally assumed that the functional consequences of stimulation with Ca2+
      -mobilizing agonists are derived exclusively from the second messenger action of
      intracellular Ca2+, acting on targets inside the cells. However, during Ca2+
      signaling events, Ca2+ moves in and out of the cell, causing changes not only in
      intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous
      cell types possess an extracellular Ca2+ "sensor" raises the question of whether
      these dynamic changes in external [Ca2+] may serve some sort of messenger
      function. We found that in intact gastric mucosa, the changes in extracellular
      [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were
      sufficient and necessary to elicit alkaline secretion and pepsinogen secretion,
      independent of intracellular [Ca2+] changes. These findings suggest that
      extracellular Ca2+ can act as a "third messenger" via Ca2+ sensor(s) to regulate
      specific subsets of tissue function previously assumed to be under the direct
      control of intracellular Ca2+.

PMID- 15240575
TI  - Proscar and propecia--a therapeutic perspective.

PMID- 15240576
TI  - Biochemical assessment and long-term monitoring in patients with acromegaly:
      statement from a joint consensus conference of the Growth Hormone Research
      Society and the Pituitary Society.

PMID- 15240577
TI  - Editorial: A blast from the past--insulin does it again!

PMID- 15240578
TI  - Regulation of the somatotropic axis by intensive insulin therapy during
      protracted critical illness.
AB  - The catabolic state of critical illness has been linked to the suppressed
      somatotropic GH-IGF-binding protein (IGFBP) axis. In critically ill patients it
      has been demonstrated that, compared with the conventional approach, which only
      recommended insulin therapy when blood glucose levels exceeded 12 mmol/liter,
      strict maintenance of blood glucose levels below 6.1 mmol/liter with intensive
      insulin therapy almost halved intensive care mortality, acute renal failure,
      critical illness polyneuropathy, and bloodstream infections. Poor blood glucose
      control in diabetes mellitus has also been associated with low serum IGF-I
      levels, which can be increased by insulin therapy. We hypothesized that intensive
      insulin therapy would improve the IGF-I axis, possibly contributing to the
      clinical correlates of anabolism. Therefore, this study of 363 patients,
      requiring intensive care for more than 7 d and randomly assigned to either
      conventional or intensive insulin therapy, examines the effects of intensive
      insulin therapy on the somatotropic axis. Contrary to expectation, intensive
      insulin therapy suppressed serum IGF-I, IGFBP-3, and acid-labile subunit
      concentrations. This effect was independent of survival of the critically ill
      patient. Concomitantly, serum GH levels were increased by intensive insulin
      therapy. The suppression of IGF-I in association with the increased GH levels
      suggests GH resistance induced by intensive insulin therapy, which was reflected
      by the decreased serum GH-binding protein levels. Intensive insulin therapy did
      not affect IGFBP-3 proteolysis, which was markedly higher in protracted
      critically ill patients compared with healthy controls. Also, intensive insulin
      therapy did not suppress the urea/creatinine ratio, a clinical correlate of
      catabolism. In conclusion, our data suggest that intensive insulin therapy
      surprisingly suppressed the somatotropic axis despite its beneficial effects on
      patient outcome. GH resistance accompanied this suppression of the IGF-I axis. To
      what extent and through which mechanisms the changes in the GH-IGF-IGFBP axis
      contributed to the survival benefit under intensive insulin therapy remain
      elusive.

PMID- 15240579
TI  - Editorial: Local control of the timing of thyroid hormone action in the
      developing human brain.

PMID- 15240580
TI  - Iodothyronine levels in the human developing brain: major regulatory roles of
      iodothyronine deiodinases in different areas.
AB  - Thyroid hormones are required for human brain development, but data on local
      regulation are limited. We describe the ontogenic changes in T(4), T(3), and
      rT(3) and in the activities of the types I, II, and III iodothyronine deiodinases
      (D1, D2, and D3) in different brain regions in normal fetuses (13-20 wk
      postmenstrual age) and premature infants (24-42 wk postmenstrual age). D1
      activity was undetectable. The developmental changes in the concentrations of the
      iodothyronines and D2 and D3 activities showed spatial and temporal specificity
      but with divergence in the cerebral cortex and cerebellum. T(3) increased in the
      cortex between 13 and 20 wk to levels higher than adults, unexpected given the
      low circulating T(3). Considerable D2 activity was found in the cortex, which
      correlated positively with T(4) (r = 0.65). Cortex D3 activity was very low, as
      was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar
      T(3) was very low and increased only after midgestation. Cerebellum D3 activities
      were the highest (64 fmol/min.mg) of the regions studied, decreasing after
      midgestation. Other regions with high D3 activities (midbrain, basal ganglia,
      brain stem, spinal cord, hippocampus) also had low T(3) until D3 started
      decreasing after midgestation. D3 was correlated with T(3) (r = -0.682) and
      rT(3)/T(3) (r = 0.812) and rT(3)/T(4) (r = 0.889). Our data support the
      hypothesis that T(3) is required by the human cerebral cortex before
      midgestation, when mother is the only source of T(4). D2 and D3 play important
      roles in the local bioavailability of T(3). T(3) is produced from T(4) by D2, and
      D3 protects brain regions from excessive T(3) until differentiation is required.

PMID- 15240581
TI  - Editorial: Toward understanding variation in responsiveness to hormones.

PMID- 15240582
TI  - Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism
      leading to decreased adrenal responsiveness to ACTH.
AB  - The ACTH receptor has a pivotal role in the regulation of adrenal cortisol
      secretion. Here, we describe a polymorphism within the transcription initiation
      site of the ACTH receptor promoter altering the consensus sequence from CTC to
      CCC. The prevalence of the polymorphism in 1266 unrelated healthy men was 80.2%
      for CTC/CTC, 19.0% for CTC/CCC, and 0.8% for CCC/CCC, respectively. In vitro
      studies using luciferase assays demonstrated a lower basal (CCC, 73 +/- 4%; CTC,
      100 +/- 5%; P = 0.02) and forskolin-stimulated (CCC, 143 +/- 13%; CTC, 194 +/-
      15%; P = 0.0008) promoter activity in the CCC construct compared with CTC. The
      clinical significance of the in vitro findings was investigated by a 6-h ACTH
      stimulation test with increasing ACTH(1-24) doses in normal subjects,
      demonstrating a blunted cortisol response in CCC/CCC subjects compared with
      CTC/CTC individuals (area under the curve, 12176 +/- 966; 16334 +/- 1051
      nmol/liter.min; P < 0.03). Accordingly, after CRH stimulation, subjects with
      CCC/CCC showed a higher ACTH/cortisol ratio (P < 0.05) suggesting a decreased
      adrenal responsiveness to endogenous ACTH. In conclusion, we describe an ACTH
      receptor promoter polymorphism that results in a lower promoter activity in vitro
      and is associated with a lower cortisol secretion to prolonged ACTH stimulation
      in vivo. This polymorphism might influence cortisol homeostasis under stress
      conditions.

PMID- 15240583
TI  - Editorial: Growth hormone treatment of "idiopathic short stature": not so fast.

PMID- 15240584
TI  - Effect of growth hormone treatment on adult height in peripubertal children with
      idiopathic short stature: a randomized, double-blind, placebo-controlled trial.
AB  - GH is often used to treat children with idiopathic short stature despite the lack
      of definitive, long-term studies of efficacy. We performed a randomized, double
      blind, placebo-controlled trial to determine the effect of GH on adult height in
      peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old,
      with marked, idiopathic short stature [height or predicted height < or = -2.5 sd
      score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week
      until they were near adult height. At study termination, adult height
      measurements were available for 33 patients after mean treatment duration of 4.4
      yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least
      squares mean +/- sem) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by
      0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH
      effect was demonstrated in terms of adult height SDS minus baseline height SDS
      and adult height SDS minus baseline predicted height SDS. Modified intent-to
      treat analysis in 62 patients treated for at least 6 months indicated a similar
      GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95%
      confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion,
      GH treatment increases adult height in peripubertal children with marked
      idiopathic short stature.

PMID- 15240585
TI  - Editorial: The determination of circulating 25-hydroxyvitamin D: no easy task.

PMID- 15240586
TI  - Assay variation confounds the diagnosis of hypovitaminosis D: a call for
      standardization.
AB  - Endemic hypovitaminosis D contributes to osteoporosis development. However,
      variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds
      the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the
      marked variability observed in serum 25OHD measurements between
      laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42
      in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations
      were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively.
      Furthermore, there was little overlap in serum 25OHD among these clinically
      similar individuals. Specifically, 17% of those measured in laboratory A but 90%
      in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently,
      serum was obtained from 10 healthy adults. Two aliquots from each individual, one
      of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories.
      Substantial variability was noted between these six laboratories. The mean serum
      25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase
      produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD
      assays yield markedly differing results; whether an individual is found to have
      low or normal vitamin D status is a function of the laboratory used. If the
      medical community is to make progress in correcting widespread hypovitaminosis D,
      25OHD measurement must be standardized.

PMID- 15240587
TI  - Editorial: Is spermatogenic damage associated with Leydig cell dysfunction?

PMID- 15240588
TI  - Impaired Leydig cell function in infertile men: a study of 357 idiopathic
      infertile men and 318 proven fertile controls.
AB  - To investigate whether an impaired Leydig cell function is present in severely
      oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels
      in 357 idiopathic infertile men were compared with levels in 318 proven fertile
      men. In addition, the T/LH ratio, E(2)/T ratio, and calculated free T index (cFT)
      were compared between the two groups.A shift toward lower serum T levels, cFT,
      and T/LH ratio and higher serum LH, E(2), and E(2)/T levels was observed in the
      group of infertile men. On average, the infertile men had 18, 26, and 34% lower
      serum T, cFT, and T/LH levels, respectively, and 19, 18, and 33% higher serum LH,
      E(2), and E(2)/T levels, respectively, than the fertile men. Twelve percent of
      the infertile men had a serum T level that fell below the 2.5 percentile of the
      fertile levels, and 15% of the infertile men had a LH level that was above the
      97.5 percentile of the fertile levels.Thus, the group of infertile men showed
      significant signs of impaired Leydig cell function in parallel to their impaired
      spermatogenesis. The association of decreased spermatogenesis and impaired Leydig
      cell function might reflect a disturbed paracrine communication between the
      seminiferous epithelium and the Leydig cells, triggered by distorted function of
      the seminiferous epithelium. On the other hand, the parallel impairment of
      spermatogenesis and Leydig cells may reflect a congenital dysfunction of both
      compartments caused by a testicular dysgenesis during fetal/infant development.

PMID- 15240589
TI  - A particular phenotype in a girl with aldosterone synthase deficiency.
AB  - Aldosterone synthase deficiency (ASD) usually presents in infancy as a life
      threatening electrolyte imbalance. A 4-wk-old child of unrelated parents was
      examined for failure to thrive and salt-wasting. Notable laboratory findings were
      hyperkalemia, high plasma renin, and low-normal aldosterone levels. Urinary
      metabolite ratios of corticosterone/18-hydroxycorticosterone and 18
      hydroxycorticosterone/aldosterone were intermediate between ASD type I and type
      II. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase
      (P450c11AS), revealed that the patient was a compound heterozygote carrying a
      previously described mutation located in exon 4 causing a premature stop codon
      (E255X) and a further, novel mutation in exon 5 that also causes a premature stop
      codon (Q272X). The patient's unaffected father was a heterozygous carrier of the
      E255X mutation, whereas the unaffected mother was a heterozygous carrier of the
      Q272X mutation. Therefore, the patient's CYP11B2 encodes two truncated forms of
      aldosterone synthase predicted to be inactive because they lack critical active
      site residues as well as the heme-binding site. This case of ASD is of particular
      interest because despite the apparent lack of aldosterone synthase activity, the
      patient displays low-normal aldosterone levels, thus raising the question of its
      source.

PMID- 15240590
TI  - Cyclical Cushing syndrome presenting in infancy: an early form of primary
      pigmented nodular adrenocortical disease, or a new entity?
AB  - Cushing syndrome is uncommon in childhood and rare in infancy. We report the case
      of a 3-yr-old child who presented with symptoms of Cushing syndrome beginning
      shortly after birth. Her hypercortisolemia was cyclical, causing relapsing and
      remitting symptoms, which eventually led to suspicions of possible Munchausen
      syndrome by proxy. Investigation at the National Institutes of Health excluded
      exogenous administration of glucocorticoids and indicated ACTH-independent
      Cushing syndrome. Paradoxical response to dexamethasone stimulation (Liddle's
      test) suggested a diagnosis of primary pigmented nodular adrenocortical disease
      (PPNAD). After bilateral adrenalectomy, both glands showed micronodular
      adrenocortical hyperplasia, but histology was not consistent with typical PPNAD.
      DNA analysis of the coding sequences of the PRKAR1A gene (associated with PPNAD
      and Carney complex) and the GNAS gene (associated with McCune-Albright syndrome)
      showed no mutations. We conclude that hypercortisolemia in infancy may be caused
      by micronodular adrenocortical hyperplasia, which can be cyclical and confused
      with exogenous Cushing syndrome. A paradoxical rise of glucocorticoid excretion
      during Liddle's test may delineate these patients. Infantile micronodular disease
      has some features of PPNAD and may represent its early form; however, at least in
      the case of the patient reported here, micronodular hyperplasia was not caused by
      coding mutations of the PRKAR1A or GNAS genes or associated with typical
      histology or any other features of Carney complex or McCune-Albright syndrome and
      may represent a distinct entity.

PMID- 15240591
TI  - Hormonal manipulation of benign metastasizing leiomyomas: report of two cases and
      review of the literature.
AB  - Benign metastasizing leiomyomas (BMLs) occur predominantly in women during
      reproductive years. The condition is characterized by uterine leiomyomas
      associated with the development, typically years later, of slow-growing
      metastatic lesions. The most commonly affected organs are the lungs, but BMLs
      have been reported in lymph nodes, deep soft tissues, mesentery, bones, the
      central nervous system, and the heart. In many cases, these lesions have an
      indolent course and are discovered rather incidentally. However, occasionally
      they can present with debilitating symptoms or even life-threatening
      complications. The presence of estrogen and progesterone receptors in these
      tumors supports their origin from uterine smooth muscle and, more importantly,
      makes them amenable to hormonal manipulation. Radical interventions, such as
      extensive tumor debulking and oophorectomy for hormonal control, although
      effective in many cases, are not always possible or desirable and carry
      significant morbidity. Here we present two cases of BMLs to illustrate the role
      of newer therapeutic agents, the estrogen receptor modulators and the aromatase
      inhibitors, in the hormonal manipulation of these tumors.

PMID- 15240592
TI  - GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism
      highlight the differential sensitivity of luteinizing hormone and follicle
      stimulating hormone to gonadotropin-releasing hormone.
AB  - Mutations in the GnRH receptor gene (GNRHR) are a cause of idiopathic
      hypogonadotropic hypogonadism. We describe a normosmic female subject with
      congenital idiopathic hypogonadotropic hypogonadism in whom treatment with
      pulsatile GnRH resulted in an unusual response. The subject not only required an
      increased dose of pulsatile GnRH for ovarian follicular development, but LH
      secretion did not increase appropriately, estradiol levels remained low, and she
      did not ovulate spontaneously. Sequencing of the GNRHR coding sequence revealed
      compound heterozygous mutations leading to amino acid substitutions [N10K+Q11K]
      and P320L. The introduction of the P320L mutation into the GnRH receptor led to
      failure of detectable ligand binding and failure of stimulation of inositol
      phosphate production and gonadotropin subunit gene promoter activity in response
      to GnRH in transiently transfected cells. The [N10K+Q11K] mutation resulted in
      reduced binding of a GnRH agonist to 25% of the wild-type receptor. In addition,
      the EC(50) value for GnRH stimulation of inositol phosphate production was
      significantly increased, and the dose-response curves for stimulation of alpha
      gonadotropin subunit, LHbeta, and FSHbeta gene transcription by GnRH were
      similarly shifted to the right. Stimulation of FSHbeta gene transcription was
      more sensitive to GnRH than LHbeta for both wild-type and [N10K+Q11K] GnRH
      receptors, resulting in a greater loss of LHbeta stimulation than FSHbeta by the
      [N10K+Q11K] mutant at any given submaximal GnRH concentration. We propose that
      the mutations in the GnRH receptor result in a rightward shift of the dose
      response curves of gonadotropin responses to pulsatile GnRH in the subject and
      unmask the differential sensitivities of LH and FSH to GnRH, resulting in low LH
      and estradiol levels despite appropriate FSH secretion and follicular growth.

PMID- 15240593
TI  - Proteinuric nephropathy in acquired and congenital generalized lipodystrophy:
      baseline characteristics and course during recombinant leptin therapy.
AB  - Generalized lipodystrophy is characterized by adipose tissue absence,
      hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly,
      and nonalcoholic steatohepatitis. In the course of recruiting patients for
      treatment with recombinant leptin, we were struck by the frequency and severity
      of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen
      were treated with recombinant leptin, and we have followed 15 on leptin for 4-36
      months. We followed renal parameters at baseline and during follow-up visits.
      Renal biopsies were performed as clinically indicated. At baseline, 22 of 25
      patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had
      macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria
      (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125
      ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin
      exhibited reduction in proteinuria, associated with reduction of hyperfiltration.
      Four patients who did not improve are discussed individually. Renal biopsy
      findings were remarkable for focal segmental glomerulosclerosis in four patients,
      membranoproliferative glomerulonephritis in two patients, and diabetic
      nephropathy in one patient. In conclusion, generalized lipodystrophy is
      associated with proteinuria and unique renal pathologies, including focal
      segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The
      majority treated with recombinant leptin demonstrated reduction in proteinuria
      and hyperfiltration.

PMID- 15240594
TI  - Weight of normal parathyroid glands in patients with parathyroid adenomas.
AB  - Although the size and weight of a parathyroid gland are frequently the only
      intraoperative determinants of abnormality, these parameters have not been
      examined in living patients with primary hyperparathyroidism (PHP). The records
      of 240 patients who underwent parathyroidectomy according to standard surgical
      practice by a single surgeon were reviewed to identify those who were
      euparathyroid after in toto removal of a histologically confirmed normal gland
      and a histologically confirmed adenoma. The 25 (86%) females and 4 (14%) males
      who met the study criteria had a mean age of 60 yr (range, 33-82 yr). The mean
      PTH level was 130.1 pg/ml (range, 58-278) before parathyroidectomy and 32.4 pg/ml
      (range, 1-68) after parathyroidectomy. The mean calcium level was 11.1 mg/dl
      (range, 10-14) before and 8.7 mg/dl (range, 8-10) after parathyroidectomy. Thirty
      four intact normal glands were removed and available for analysis. Their mean
      weight was 62.4 +/- 31.6 mg (range, 18-161 mg), and 15 (44%) weighed 60 mg or
      more. The mean weight of the adenomas was 553.7 +/- 520.5 mg (range, 66-2536).
      Adenomas were clearly distinguished from normal glands by cellularity, stromal
      fat, and intracellular fat in chief cells. The weight of normal parathyroid
      glands removed at surgery in patients with PHP may be greater than that reported
      in autopsy studies. Therefore, certain histological features are a better measure
      than weight in determining whether a gland is normal, and intraoperative
      identification of slightly enlarged glands should not lead to immediate subtotal
      parathyroidectomy.

PMID- 15240595
TI  - Molecular profiling distinguishes papillary carcinoma from benign thyroid
      nodules.
AB  - Recently we identified a molecular basis for differentiating benign and malignant
      follicular thyroid tumors. The purpose of these studies was to determine whether
      molecular analysis can be used to differentiate papillary thyroid carcinomas from
      benign thyroid nodules. Gene expression patterns of 14 papillary thyroid
      carcinomas and 21 benign tumors were analyzed by oligonucleotide array analysis.
      The carcinomas included seven classical papillary thyroid carcinomas (PTC) and
      seven follicular variant of PTC (FVPTC), and the benign tumors included 14
      follicular adenomas and seven hyperplastic nodules. A hierarchical clustering
      analysis was performed to examine the groups for potential differences. The
      combined PTC and FVPTC groups had a distinct gene expression profile compared
      with the benign lesions. The sensitivity for a diagnosis of carcinoma was 93%,
      with a 100% specificity (one FVPTC clustered with the benign nodules). Cancer
      gene profiles contained both known (Met and galectin-3) and previously
      unidentified genes. Gene profiling is a reliable means of distinguishing PTC,
      FVPTC, and benign tumors of the thyroid. These gene profiles may provide insight
      into the pathogenesis of papillary thyroid carcinoma and may ultimately enhance
      the preoperative diagnosis of thyroid nodules on a molecular basis.

PMID- 15240596
TI  - Efficacy and tolerability of an individualized dosing regimen for adult growth
      hormone replacement therapy in comparison with fixed body weight-based dosing.
AB  - To determine whether an individualized dose titration regimen (ID) for adult GH
      replacement therapy would have similar efficacy and better tolerability than a
      fixed body weight-based dosing regimen (FD), 387 adults with GH deficiency were
      randomized to FD (n = 200) or ID (n = 187) for 32 wk. In FD, subjects received
      sequentially 4, 8, and 12 microg/kg.d GH. ID was started at 0.2 mg/d and
      increased by 0.2-mg/d increments, based on clinical and serum IGF-I responses, to
      a maximum of 0.8 mg/d. Increases (mean +/- sd) in serum IGF-I were similar in
      both groups (FD, 110.2 +/- 87.8 vs. ID, 99.6 +/- 77.7 microg/liter, P = 0.20)
      despite higher final GH doses in FD (0.70 +/- 0.32 vs. 0.54 +/- 0.22 mg/d, P <
      0.001). Favorable changes in several efficacy measures were observed with no
      significant differences between the FD and ID groups: lean body mass increased;
      health-related quality of life improved; and abdominal fat mass, hip
      circumference, sum of skinfolds, and total and low-density lipoprotein
      cholesterol decreased. The decrease in fat mass was greater with FD than ID for
      men (-2.7 +/- 2.7 kg vs. -1.8 +/- 2.5 kg, P = 0.04) but not for women (-2.1 +/-
      2.4 vs. -2.0 +/- 3.8 kg). The change in waist circumference was greater with FD
      than ID for women but not for men. There was a significant reduction of systolic
      blood pressure in ID but not in FD. The adverse event profile was similar between
      FD and ID except that ID had a lower occurrence of peripheral edema (9.1% vs.
      16.5%, P = 0.03) and rash (1.1% vs. 5.5%, P = 0.02) than FD. In summary, the use
      of ID resulted in improved tolerability and similar efficacy compared with FD. We
      conclude that GH replacement therapy should be initiated at a low dose and
      titrated to a dose producing maximal benefits without adverse side effects and an
      IGF-I level within the age- and sex-adjusted normal range.

PMID- 15240597
TI  - Pharmacokinetic and pharmacodynamic characteristics of a long-acting growth
      hormone (GH) preparation (nutropin depot) in GH-deficient children.
AB  - Long-term GH replacement therapy is indicated for children with growth failure
      due to GH deficiency (GHD). We evaluated the feasibility of administering a long
      acting GH preparation [Nutropin Depot (somatropin, rDNA origin) for injectable
      suspension] to prepubertal children with GHD by examining pharmacokinetic and
      pharmacodynamic response parameters after single or multiple doses. Data were
      collected from three studies involving 138 children treated with Nutropin Depot
      0.75 mg/kg once per month, 0.75 mg/kg twice per month, or 1.5 mg/kg once per
      month. Twenty-two patients underwent intensive sampling to estimate mean peak
      serum GH concentrations (C(max)) and time to achieve C(max) for GH and IGF-I.
      Thereafter, weekly serum concentrations were measured and compared with baseline.
      C(max) and area under the curve were approximately proportional to the dose
      administered. Fractional area under the curve data indicate that at least 50% of
      GH exposure occurs during the first 2 d after administration. Serum GH levels
      remained above 1 microg/liter for 11-14 d. IGF-I levels remained above baseline
      for 16-20 d, but increases were not proportional to dose. After multiple doses
      over a 6-month period, peak and trough concentrations showed no progressive
      accumulation of GH, IGF-I, or IGF binding protein-3. Nutropin Depot
      administration once or twice per month provides serum levels of GH and IGF-I
      expected to promote growth, without accumulation of GH, IGF-I, or IGF binding
      protein-3, in children with GHD.

PMID- 15240598
TI  - Use of percutaneous estrogen gel for induction of puberty in girls with Turner
      syndrome.
AB  - The aim of pubertal induction by estrogen in hypogonadic girls is to achieve
      physical and psychological development similar to that in natural puberty. We
      investigated the use of percutaneous estradiol gel for induction of puberty in
      girls with Turner syndrome (TS).Twenty-three girls with TS and hypogonadism were
      included in the study. The initial percutaneous dose of 0.1 mg ended as 1.5 mg in
      the fifth year. The efficacy of the treatment was monitored by measuring height,
      weight, skeletal age, pubertal status, and serum hormone levels and gynecological
      ultrasonographic examinations throughout the study. Mean serum estradiol
      concentrations increased from 22.2 pmol/liter at baseline to 162.2 pmol/liter,
      and mean FSH levels decreased from 77.4 IU/liter at baseline to 19.2 IU/liter
      after 5 yr. There were no significant differences between GH users and nonusers
      with regard to height sd score, weight sd score, bone age acceleration, or adult
      height. The development of secondary sexual characteristics and uterine growth
      progressed gradually during the study. All girls reached at least stage B4P4.
      With percutaneous estradiol gel, the development of secondary sexual
      characteristics and uterine growth proceeded gradually, mimicking natural
      puberty. Estradiol gel was safe, easy to use, and well accepted by the subjects
      and provides an excellent way to individualize pubertal induction.

PMID- 15240599
TI  - Hypothalamic-pituitary-adrenal axis response and recovery from high-intensity
      exercise in women: effects of aging and fitness.
AB  - This study tested the hypotheses that aging is associated with prolonged recovery
      after a challenge to the hypothalamic-pituitary-adrenal axis (acute exercise) and
      that aerobic fitness is associated with a blunting of the age-related loss of
      negative feedback sensitivity. Young (27 +/- 2.8 yr, n = 9), older (64.6 +/- 1.4
      yr, n = 11), and older-fit women (66.3 +/- 2.2 yr, n = 11) underwent a short bout
      of treadmill exercise at high (but submaximal) intensity. The exercise trial
      elicited significant increases in heart rate, blood pressure, ACTH, and cortisol
      (P < 0.001). Although the young and the older women exhibited similar cortisol
      response to the trial and throughout the recovery period, the older women had a
      slower decrease of ACTH levels (P < 0.05), suggesting reduced negative feedback
      sensitivity with aging. Between the two groups of older women, the older-fit
      group had significantly greater rate of recovery of ACTH levels (P < 0.05)
      compared with the older unfit women. However, older fit women had greater
      cortisol production during the recovery period (P < 0.05), suggesting greater
      adrenal sensitivity to ACTH. These results suggest that aging is associated with
      changes in the dynamic function of the hypothalamic-pituitary-adrenal axis and
      that these changes are attenuated by aerobic fitness.

PMID- 15240600
TI  - Physiological testosterone replenishment in healthy elderly men does not
      normalize pituitary growth hormone output: evidence against the connection
      between senile hypogonadism and somatopause.
AB  - Normal aging in men is accompanied by lower serum testosterone (T), GH, and IGF-I
      concentrations. The mechanisms of the age-related diminution in the activity of
      the somatotropic axis (somatopause) are uncertain. Several explanations have been
      proposed, including a lower hypothalamic GHRH output. The aim of the present
      study was to test the hypothesis that the physiological hypogonadism that
      accompanies normal aging is responsible for GHRH deficiency. We assessed the
      suppressibility of spontaneous and GHRH-stimulated GH secretion by a specific
      competitive GHRH receptor antagonist in seven elderly (61-76 yr old) and six
      young (20-23 yr old) healthy nonobese men. Elderly men then received transdermal
      T (5 mg/d) for 5-6 wk and had the same experiment repeated. Mean final total T,
      free T, and dihydrotestosterone increased in elderly men [521.5 +/- 56.3 vs.
      395.4 +/- 57.2 ng/dl (P = 0.021), 13.8 +/- 1.3 vs. 10.1 +/- 1.7 pg/ml (P =
      0.017), and 71.4 +/- 8.9 vs. 41 +/- 8.1 ng/dl (P = 0.004), respectively] to the
      levels found in their younger controls, but estradiol did not change (19.1 +/-
      2.5 vs. 18.5 +/- 2.9 pg/ml; P = 0.67). GH pulse frequency or amplitude and
      maximum GH were not altered, and the integrated GH concentrations actually
      decreased. The percent suppression of GH output in the elderly did not change
      during GHRH antagonist infusion (35.8 +/- 2.6% vs. 27.7 +/- 6.5%; P = 0.29). We
      conclude that the T deficiency of old age is unlikely to be the proximate cause
      of the somatopause.

PMID- 15240601
TI  - Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident
      vertebral fractures in elderly men and women: the Rotterdam Study.
AB  - In an age-matched, case-control study, we investigated the association between
      endogenous sex steroid hormones and incident vertebral fractures in both elderly
      men and women (aged 67.7 +/- 6.8 yr). Drawn from the Rotterdam Study,
      participants required radiographs of the lumbar spine at both baseline and follow
      up (average time of follow-up, 6.5 yr) and frozen blood samples, taken at
      baseline. One hundred and seventy-eight men (45 cases) and 454 women (115 cases)
      were thus selected. Serum estradiol, SHBG, testosterone, and insulin were
      measured, along with bone mineral density at both spine and hip. Women in the
      lowest tertile of serum estradiol (< or =15.5 pmol/liter) had a 2.1 times
      increased risk (95% confidence interval, 1.3-3.5) of incident vertebral
      fractures, independently of bone mineral density measured at either site. SHBG
      levels in the lowest two tertiles were associated with a 50% reduction in
      incident vertebral fracture risk. Women with a combination of both low estradiol
      and high SHBG had a 7.8 times higher risk of an incident vertebral fracture (95%
      confidence interval, 2.7-22.5; P < 0.001), adjusted for age and weight. This
      increased risk did not change when non-SHBG-bound estradiol was used instead of
      total estradiol. For men, no clear association was found, possibly due to
      insufficient power. No clear association between testosterone and incident
      vertebral fractures was observed in either men or women.

PMID- 15240602
TI  - Relationship between follicle-stimulating hormone levels at the beginning of the
      human menstrual cycle, length of the follicular phase and excreted estrogens: the
      FREEDOM study.
AB  - Although reproductive aging has been separately related to elevated FSH and
      shorter follicular phase (FP), the direct association between both parameters has
      not been investigated. Also, the exact effects of increased FSH on estrogen
      production are yet to be established.A large database of daily urinary
      concentrations of FSH, LH, and estrone 3-glucuronide (E1G) from 37 regularly
      menstruating women (median 11 cycles per patient) was used. Initial FSH levels
      (iFSH) were estimated as the mean value of d 1-5. The day of E1G take-off (ETO)
      was determined by an algorithm, and accordingly, the FP was divided into early (d
      1 to ETO) and late (ETO+1 to LH peak). FP maximum and integrated E1G were
      calculated. Subjects were distributed according to their mean iFSH into three
      categories (</=5, >5 to 10, and >10 IU/liter). There was a gradual decrease in FP
      length with increasing category (15.2 +/- 3.8, 14.1 +/- 3.6, and 13 +/- 2.6 d,
      respectively; P < 0.0001). A similar effect occurred in early FP (7.5 +/- 4, 6.4
      +/- 3.7, and 5.4 +/- 2.7; P < 0.0001); in contrast, late FP was unaffected (7.7
      +/- 2.1, 7.7 +/- 2.1, and 7.6 +/- 2.4; P = 0.86). No consistent increase in E1G
      was found with advancing iFSH category; however, women with mean initial LH
      higher than 6 IU/liter had significantly elevated maximum (P < 0.0001) and
      integrated (P = 0.002) E1G.FP length decreases in parallel with increasing iFSH,
      with a selective effect on the early FP. Increased FSH does not affect E1G;
      however, elevated initial LH level was related to higher E1G.

PMID- 15240603
TI  - Genetic and environmental influences on thyroid hormone variation in Mexican
      Americans.
AB  - Thyroid hormones play major roles in the regulation of a wide range of metabolic
      and physiologic processes, but the genes and environmental factors that affect
      normal, quantitative variation in thyroid hormone concentrations are largely
      unknown. Using quantitative genetic methods, we evaluated the effects of genes
      and environmental factors on thyroid hormone variation in 586 women and 425 men
      from 27 randomly ascertained Mexican-American families from the San Antonio
      Family Heart Study. Data were available on free and total T(4), free and total
      T(3), TSH, thyroglobulin, and T(4)-binding globulin, as well as on covariates,
      including sex, age, weight, lifestyle habits, physical activity, and others.
      These covariates accounted for 2-18% of total phenotypic variation, whereas genes
      accounted for 26-64% of the variation. Overall, free T(3) had the highest
      heritability, which is noteworthy because it is the most biologically active
      thyroid hormone and accounts for the vast majority of metabolic and physiologic
      effects of thyroid hormones. Our results indicate that genes account for a
      substantial portion of variation in human thyroid hormone levels, and suggest
      that further studies to identify the genes involved in this variation could
      reveal important insights into the processes that govern thyroid-mediated
      metabolism.

PMID- 15240604
TI  - Rapid rise in serum thyrotropin concentrations after thyroidectomy or withdrawal
      of suppressive thyroxine therapy in preparation for radioactive iodine
      administration to patients with differentiated thyroid cancer.
AB  - Patients with differentiated thyroid cancer are often treated transiently with
      T(3) in preparation for radioactive iodine (RAI) therapy. We questioned the value
      of using T(3) transiently in patients requiring RAI therapy. Two groups of
      patients requiring RAI therapy were investigated. One group included patients
      studied immediately after thyroidectomy, whereas the other included those
      withdrawn from chronic suppressive T(4) therapy that followed thyroidectomy and
      postoperative RAI ablation. Serum TSH concentrations were serially measured two
      to three times weekly until they reached more than 30 mU/liter, after which RAI
      therapy was administered. Serum TSH concentrations reached more than 30 mU/liter
      8-26 d (mean +/- sd, 14.2 +/- 4.8) after thyroidectomy or 9-29 (18.1 +/- 4.1) d
      after T(4) withdrawal. That level of TSH elevation was achieved 18 d after
      thyroidectomy and 22 d after T(4) withdrawal in more than 95% of patients.
      Minimal symptoms of hypothyroidism were noted in either group when RAI was
      administered. Serum TSH concentrations increased rapidly without transient
      therapy with T(3). To minimize symptoms of hypothyroidism, serum TSH levels
      should be measured twice weekly, starting 10 d after thyroidectomy or T(4)
      withdrawal. The data cast doubt about the value and benefits from using T(3) in
      preparing patients for RAI therapy.

PMID- 15240605
TI  - Effects of testosterone administration on growth hormone pulse dynamics in human
      immunodeficiency virus-infected women.
AB  - The effects of testosterone administration on the GH axis in androgen-deficient
      HIV-infected women are unknown. In this study, we determined the effects of
      transdermal testosterone administration on GH secretory dynamics and pulse
      characteristics in this population. GH-IGF-I parameters were determined in
      response to testosterone (4.1 mg/patch, twice a week; estimated delivery rate,
      150 microg/d) vs. placebo over 6 months in 31 HIV-infected women. IGF-I increased
      significantly in the testosterone-treated compared with the placebo-treated
      patients [37 (-4, 73) vs. -30 (-98, 39) ng/ml, P = 0.01; 4.8 (-0.5, 9.6) vs. -3.9
      (-12.8, 5.1) nmol/liter]. GH pulse frequency increased significantly in the
      testosterone-treated compared with the placebo-treated subjects [1.0 (1.0, 2.0)
      vs. 0.0 (-0.5, 1.5) peaks per 12 h, respectively; P = 0.02]. Before testosterone
      administration, overnight GH pulse amplitude was significantly related to IGF-I
      in univariate (r = 0.41, P = 0.03) and multivariate regression analysis; however,
      free testosterone, estradiol, and body mass index were not significantly
      correlated with baseline IGF-I. In contrast, after 6 months of treatment with
      testosterone, the change in IGF-I was significantly correlated to the change in
      free testosterone in univariate (r = 0.40, P = 0.04) and multivariate regression
      analysis. For each 1.0 pg/ml (3.5 pmol/liter) increase in free testosterone, IGF
      I increased 19 ng/ml (2.5 nmol/liter), controlling for estradiol, body mass
      index, and GH pulse parameters (r(2) = 0.64). We demonstrate that IGF-I increases
      in response to physiologic, transdermal testosterone in HIV-infected women. The
      mechanism of this effect is unknown, but may involve a direct effect of
      testosterone on IGF-I, independent of changes in GH pulse dynamics.

PMID- 15240606
TI  - Longitudinal study on growth and body mass index before and after diagnosis of
      childhood craniopharyngioma.
AB  - We analyzed whether childhood craniopharyngioma predisposes to obesity and growth
      impairment. Height/length, body mass index (BMI), and hypothalamic involvement
      were evaluated in 90 patients at standardized ages and time points before, after,
      and at the time of diagnosis. Relevant decreases in height sd score (SDS) started
      at 10-12 months of age and persisted until diagnosis of childhood
      craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5
      yr of age. Postoperative BMI SDS (yr 1-6) had a weak positive correlation with
      BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic
      tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS
      at age 6-7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and
      independent impacts on the development of obesity. Patients with hypothalamic
      involvement (n = 48) presented lower ponderal index and BMI SDS at birth and
      higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual
      follow-up (P < 0.001) compared with patients without hypothalamic involvement (n
      = 42). From childhood (3.5-4 yr) to the time of diagnosis, growth rates were
      reduced for patients with hypothalamic tumor involvement. Patients without
      hypothalamic involvement presented reduced growth rates in early infancy (age 10
      12 months) that persisted until diagnosis. We conclude that reduced growth rates
      occur quite early in history; BMI SDS increases occur later and are predictive of
      obesity. Hypothalamic involvement is the major risk factor for obesity in
      patients with childhood craniopharyngioma.

PMID- 15240607
TI  - Malignant disease and cardiovascular morbidity in hypopituitary adults with or
      without growth hormone replacement therapy.
AB  - A retrospective comparison was performed between 1411 hypopituitary adults
      without GH replacement [mean age, 56.9 (sd 18.6) yr] and the normal population in
      terms of fatal and nonfatal morbidity. A similar prospective comparison was then
      made in 289 hypopituitary patients on long-term GH replacement [mean age, 47.6
      (sd 14.8) yr; mean duration of GH treatment, 60 months]. In the 1411
      hypopituitary patients without GH replacement, overall mortality (P < 0.001), and
      the rates of myocardial infarctions (P < 0.01), cerebrovascular events (P <
      0.001), and malignancies (P < 0.001) were increased compared with the normal
      population. Colorectal cancer was the most common malignancy in this cohort (P <
      0.001 vs. the background population). In the 289 hypopituitary patients on GH
      replacement, overall mortality and the rate of malignancies were similar to the
      normal population. In the hypopituitary adults on GH therapy, the rate of
      myocardial infarctions was lower than that in the background population (P <
      0.05), and there was a tendency toward an increased rate of cerebrovascular
      events. In conclusion, overall mortality and the rate of myocardial infarctions
      were increased in hypopituitary patients without GH replacement. An increased
      rate of malignancies was observed in the hypopituitary adults without GH therapy,
      with a predominance of colorectal cancer. GH replacement appeared to provide
      protection from myocardial infarctions. The rate of cerebrovascular events tended
      to be increased also in hypopituitary adults on GH therapy.

PMID- 15240608
TI  - The effect of testosterone replacement on endogenous inflammatory cytokines and
      lipid profiles in hypogonadal men.
AB  - Testosterone has immune-modulating properties, and current in vitro evidence
      suggests that testosterone may suppress the expression of the proinflammatory
      cytokines TNFalpha, IL-1beta, and IL-6 and potentiate the expression of the
      antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo
      controlled, crossover study of testosterone replacement (Sustanon 100) vs.
      placebo in 27 men (age, 62 +/- 9 yr) with symptomatic androgen deficiency (total
      testosterone, 4.4 +/- 1.2 nmol/liter; bioavailable testosterone, 2.4 +/- 1.1
      nmol/liter). Compared with placebo, testosterone induced reductions in TNFalpha (
      3.1 +/- 8.3 vs. 1.3 +/- 5.2 pg/ml; P = 0.01) and IL-1beta (-0.14 +/- 0.32 vs.
      0.18 +/- 0.55 pg/ml; P = 0.08) and an increase in IL-10 (0.33 +/- 1.8 vs. -1.1 +/
      3.0 pg/ml; P = 0.01); the reductions of TNFalpha and IL-1beta were positively
      correlated (r(S) = 0.588; P = 0.003). In addition, a significant reduction in
      total cholesterol was recorded with testosterone therapy (-0.25 +/- 0.4 vs. 
      0.004 +/- 0.4 mmol/liter; P = 0.04). In conclusion, testosterone replacement
      shifts the cytokine balance to a state of reduced inflammation and lowers total
      cholesterol. Twenty of these men had established coronary disease, and because
      total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines
      mediate the development and complications associated with atheromatous plaque,
      these properties may have particular relevance in men with overt vascular
      disease.

PMID- 15240609
TI  - Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo
      controlled trial.
AB  - Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral
      density (BMD). A randomized, double-blind, placebo-controlled trial was conducted
      to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in
      patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet
      surgical guidelines or refused surgery. Forty-four patients randomized to placebo
      or active treatment arms were stratified for gender. At 12 months, patients
      taking placebo crossed over to active treatment. All patients were on active
      treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS),
      femoral neck, total hip, and distal one third radius was measured every 6 months
      by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific
      alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide
      (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2
      yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P <
      0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased
      significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77%
      se; P < 0.001) from baseline and remained stable over the next 12 months of
      therapy. BMD at the one third radius site did not show any statistically
      significant change in the alendronate-treated group at 12 or 24 months of
      therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) =
      0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in
      comparison with baseline. The placebo group, when crossed over to alendronate at
      12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P
      = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the
      total hip site in comparison with baseline. There was no statistically
      significant change seen in the placebo group at 12 months at any BMD site and no
      significant change at 24 months for the distal one third radius or femoral neck
      sites. Alendronate was associated with marked reductions in bone turnover markers
      with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5%
      se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = 
      15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11;
      +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively)
      of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum
      calcium (total and ionized), PTH, and urine calcium did not change with
      alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS
      at 12 and 24 months from baseline values. Significant reductions in bone turnover
      occur with stable serum calcium and PTH levels. Alendronate may be a useful
      alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

PMID- 15240610
TI  - Augmentation of growth hormone secretion after testosterone treatment in boys
      with constitutional delay of growth and adolescence: evidence against an increase
      in hypothalamic secretion of growth hormone-releasing hormone.
AB  - The increase in pituitary GH secretion that occurs during mid-late puberty in
      boys follows an increase in circulating testosterone (T) concentration; the
      direct mechanism by which this occurs is unknown. We hypothesized that T
      increases GH secretion during puberty by augmenting hypothalamic output of GHRH.
      Using constant infusions of a GHRH antagonist, we tested this hypothesis in six
      early pubertal boys with constitutional delay of growth and adolescence who had a
      mean chronological age of 14.0 +/- 0.3 yr and mean bone age of 11.4 +/- 0.2 yr.
      Blood samples were obtained from subjects every 15 min for 24 h during the
      overnight infusion of normal saline (2000-0600 h) and again during the overnight
      infusion of GHRH antagonist (0.33 microg/kg/h) the following night. Subjects then
      received transdermal T (5-mg patch) for 12 h nightly and were studied again after
      4 wk of treatment. Serum samples were assayed for GH and total ghrelin; the
      percent suppression of GH during GHRH antagonist infusion was calculated. Morning
      serum T rose from 0.44 +/- 0.09 to 4.43 +/- 0.74 microg/liter (P = 0.005). T
      treatment was associated with a 92.6% increase in mean nocturnal GH secretion
      area under the curve (830 +/- 177 to 1599 +/- 340 microg/24 h.liter). Infusion of
      GHRH-antagonist suppressed mean nocturnal GH area under the curve by 29.1% before
      T treatment (830 +/- 177 to 621 +/- 168 microg/24 h.liter), and by 29.4% after T
      treatment (1599 +/- 340 to 1182 +/- 249 microg/24 h.liter; P = 0.99). Somatotroph
      sensitivity to GHRH was tested with 0.1- and 1.0-microg/kg doses of GHRH-44 iv;
      GH response did not change with regard to T treatment. The mean 24-h
      concentration of total ghrelin was unchanged with regard to T treatment. In
      summary, nightly transdermal T administration in six boys with constitutional
      delay of growth and adolescence increased GH output almost 2-fold, whereas the
      degree of GH suppressibility by GHRH antagonist remained unchanged. We conclude
      that the T-associated augmentation of GH secretion during early puberty in boys
      is unlikely to involve an absolute increase in hypothalamic GHRH output.

PMID- 15240612
TI  - Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not
      differentially affected by diet composition.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of
      reproductive age associated with obesity. It may involve dysregulation of
      ghrelin, a hormone implicated in appetite regulation. The effect of diet
      composition on ghrelin is unclear. Overweight women with and without PCOS were
      randomized to a high-protein (40% carbohydrate, 30% protein; 10 PCOS, six non
      PCOS) or standard protein diet (55% carbohydrate, 15% protein; 10 PCOS, six non
      PCOS) for 12 wk of energy restriction and 4 wk of weight maintenance. Diet
      composition had no effect on fasting or postprandial ghrelin or measures of
      satiety. Non-PCOS subjects had a 70% higher fasting baseline ghrelin (P = 0.011),
      greater increase in fasting ghrelin (57.5 vs. 34.0%, P = 0.033), and greater
      maximal decrease in postprandial ghrelin after weight loss (-144.1 +/- 58.4 vs. 
      28.9 +/- 14.2 pg/ml, P = 0.02) than subjects with PCOS. Subjects with PCOS were
      less satiated (P = 0.001) and more hungry (P = 0.007) after a test meal at wk 0
      and 16 than subjects without PCOS. Appetite regulation, as measured by subjective
      short-term hunger and satiety and ghrelin homeostasis, may be impaired in PCOS.

PMID- 15240611
TI  - Changes in serum receptor activator of nuclear factor-kappaB ligand,
      osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced
      osteoporosis treated with human parathyroid hormone (1-34).
AB  - Changes in biochemical markers of bone turnover following intermittent injections
      of human (h)PTH (1-34) suggest that bone formation is initially favored over bone
      resorption. hPTH (1-34) is also known to influence osteoclast maturation and
      activity through modulation of osteoblast-derived cytokines, such as receptor
      activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), IL-6,
      and IL-6 soluble receptor (IL-6sR). In this experiment, we investigated the
      changes in serum levels of soluble RANKL (sRANKL), OPG, IL-6, and IL-6sR in
      patients with glucocorticoid-induced osteoporosis treated with hPTH (1-34). Fifty
      one postmenopausal women with glucocorticoid-induced osteoporosis were randomized
      to receive 12 months of 400 U hPTH (1-34) ( approximately 40 microg) daily and
      standard hormone replacement therapy, or hormone replacement therapy alone. Serum
      levels of sRANKL, OPG, IL-6, and IL-6sR were measured at baseline, 1 month, and
      every 3 months thereafter for a total of 24 months. hPTH (1-34) caused a rapid
      and significant increase in sRANKL within 1 month, and the levels remained
      elevated throughout the duration of therapy. IL-6 and IL-6sR increased
      significantly within 1 month, but returned to baseline levels more rapidly. In
      contrast, OPG was mildly suppressed beginning 6 months after hPTH therapy. These
      data support the hypothesis that hPTH (1-34) initially stimulates osteoblast
      maturation and function, which in turn leads to osteoclast activation and a
      gradual rebalancing of bone formation and resorption.

PMID- 15240613
TI  - Midnight salivary cortisol for the initial diagnosis of Cushing's syndrome of
      various causes.
AB  - We assessed the value of midnight salivary cortisol for the initial diagnosis of
      Cushing's syndrome. Sixty-three patients with various causes of Cushing's
      syndrome (37 with Cushing's disease, 17 with adrenal Cushing's syndrome, and nine
      with ectopic ACTH syndrome) and 54 control subjects with simple obesity were
      studied. All patients with Cushing's syndrome excreted more than 90 microg
      urinary free cortisol (UFC)/d (248 nmol/d), and all controls excreted less than
      90 microg/d UFC. All patients with Cushing's syndrome had a midnight salivary
      cortisol concentration above 2.0 ng/ml (5.52 nmol/liter), whereas only three
      controls did so [2.0 ng/ml (5.52 nmol/liter); 2.05 ng/ml (5.66 nmol/liter); and
      3.6 ng/ml (9.96 nmol/liter)]. This cut-off provides a sensitivity of 100% and a
      specificity of 96%. In patients with Cushing's syndrome, midnight salivary
      cortisol concentrations were correlated with UFC collected over the same period
      of time (0800-0800 h). Salivary cortisol measurements taken every 4 h showed a
      typical lack of circadian variation. The daily measurement of midnight salivary
      cortisol concentrations for 2 wk or more in five other out-patients (with obvious
      Cushing's disease, subclinical adrenal Cushing's syndrome, suspected Cushing's
      syndrome, pituitary incidentaloma, and prolactinoma) demonstrated the clinical
      utility of this factor. Measuring midnight salivary cortisol is an easy and
      noninvasive means of diagnosing hypercortisolism. Its diagnostic accuracy is
      identical to, if not better than, that of previously described gold standards.

PMID- 15240614
TI  - Plasma ghrelin in obesity before and after weight loss after laparoscopical
      adjustable gastric banding.
AB  - Weight reduction after gastric bypass surgery has been attributed to a decrease
      of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin.
      This study examined effects of long-term weight loss after laparoscopical
      adjustable gastric banding on plasma ghrelin and leptin concentrations and their
      relationship with insulin action. Severely obese patients (15 women, three men,
      36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral
      glucose tolerance tests to assess parameters of insulin sensitivity and secretion
      every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/-
      5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This
      was associated with lower (P < 0.0001) plasma glucose, insulin, insulin
      resistance, waist circumference, and blood pressure. Plasma leptin decreased from
      27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001).
      Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53
      pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6
      months). At 6 and 12 months, ghrelin levels correlated negatively with fasting
      plasma insulin levels and hepatic insulin extraction but not with body mass or
      insulin action. In conclusion, prolonged weight loss results in a rise of fasting
      ghrelin concentrations that correlates with fasting insulin concentrations but
      not improvement of insulin sensitivity.

PMID- 15240615
TI  - Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical
      assessment in 45 patients with Noonan syndrome.
AB  - We report on PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) mutation
      analysis and clinical assessment in 45 patients with Noonan syndrome. Sequence
      analysis was performed for all of the coding exons 1-15 of PTPN11, revealing a
      novel 3-bp deletion mutation and 10 recurrent missense mutations in 18 patients.
      Clinical assessment showed that 1) the growth pattern was similar in mutation
      positive and mutation-negative patients, with no significant difference in birth
      length [-0.6 +/- 2.2 sd (n = 10) vs. -0.6 +/- 1.4 sd (n = 21); P = 0.95],
      childhood height [-2.6 +/- 1.1 sd (n = 14) vs. -2.1 +/- 1.6 sd (n = 23); P =
      0.28], or target height [-0.4 +/- 0.9 sd (n = 14) vs. -0.2 +/- 0.7 sd (n = 17); P
      = 0.52]; 2) pulmonary valve stenosis was more frequent in mutation-positive
      patients than in mutation-negative patients (10 of 18 vs. 6 of 27; P = 0.02), as
      was atrial septal defect (10 of 18 vs. 4 of 27; P = 0.005), whereas hypertrophic
      cardiomyopathy was present in five mutation-negative patients only; and 3) other
      features were grossly similar in the prevalence between mutation-positive and
      mutation-negative patients, but hematological abnormalities, such as bleeding
      diathesis and juvenile myelomonocytic leukemia, were exclusively present in
      mutation-positive patients (5 of 18 vs. 0 of 27; P = 0.007). The results suggest
      that PTPN11 mutations account for approximately 40% of Noonan syndrome patients,
      as has been reported previously. Furthermore, assessment of clinical features, in
      conjunction with data reported previously, implies that the type of
      cardiovascular lesions and the occurrence of hematological abnormalities are
      different in mutation-positive and mutation-negative patients, whereas the
      remaining findings are similar in the two groups of patients.

PMID- 15240616
TI  - Risk for ischemic heart disease and all-cause mortality in subclinical
      hypothyroidism.
AB  - We investigated possible associations between subclinical hypothyroidism and
      atherosclerotic diseases (ischemic heart disease and cerebrovascular disease) and
      mortality. Of 2856 participants (mean age 58.5 yr) in a thyroid disease screening
      between 1984 and 1987, 257 subjects with subclinical hypothyroidism (TSH > 5.0
      mU/liter) and 2293 control subjects (TSH range 0.6-5.0 mU/liter) were analyzed.
      In the baseline cross-sectional analysis, subclinical hypothyroidism was
      associated with ischemic heart disease independent of age, systolic blood
      pressure, body mass index, cholesterol, smoking, erythrocyte sedimentation rate,
      or presence of diabetes mellitus [odds ratio (OR), 2.5; 95% confidence interval
      (95% CI), 1.1-5.4 in total subjects and OR, 4.0; 95% CI, 1.4-11.5 in men] but not
      in women. However, there was no association with cerebrovascular disease (OR,
      0.9; 95% CI, 0.4-2.4). We were unable to detect an influence of thyroid antibody
      presence on the association between subclinical hypothyroidism and ischemic heart
      disease. In a 10-yr follow-up study until 1998, increased mortalities from all
      causes in yr 3-6 after baseline measurement were apparent in men with subclinical
      hypothyroidism (hazard ratio, 1.9-2.1) but not in women, although specific causes
      of death were not determined. Our results indicate that subclinical
      hypothyroidism is associated with ischemic heart disease and might affect all
      cause mortality in men.

PMID- 15240617
TI  - Pituitary magnetic resonance imaging findings do not influence surgical outcome
      in adrenocorticotropin-secreting microadenomas.
AB  - The pituitary origin of ACTH secretion in ACTH-dependent hypercortisolism can be
      difficult to assess, as magnetic resonance imaging (MRI) frequently fails to
      identify ACTH-secreting microadenomas or, on the contrary, may give false
      positive images of microadenomas. The choice of therapeutic option for patients
      with such normal MRI findings is controversial. Some groups propose routinely
      pituitary surgery, whereas others consider that neurosurgical exploration may be
      less successful and more harmful, and therefore prefer other types of management.
      The aim of this study was to compare surgical outcomes between patients with
      Cushing's disease (CD) and normal vs. positive pituitary MRI findings. Fifty-four
      patients (44 women and 10 men) with CD, operated on after 1996 in two centers
      (Kremlin-Bicetre and Bordeaux) and followed postoperatively during a mean period
      of 19.9 +/- 22.7 months (range, 1-89 months), were enrolled in this retrospective
      study. Twenty-eight patients had normal pituitary MRI findings, and the pituitary
      origin of ACTH was established by bilateral petrosal sinus sampling in all of
      these cases. Twenty-six patients had positive MRI findings clearly showing a
      microadenoma. The two groups were not significantly different in terms of the sex
      ratio, age, frequency of hypertension, or diabetes, basal 24-h urinary free
      cortisol levels and follow-up. All of the patients were operated on by two
      experienced neurosurgeons using the same surgical protocol. Selective
      adenomectomy was performed when a tumor was identified, and subtotal
      hypophysectomy was performed when the lesion was uncertain or when no tumor was
      found during surgical exploration. Respectively, 50% and 84% of patients with
      normal and positive MRI results underwent adenomectomy (P < 0.05). A pituitary
      adenoma (confirmed by pathological examination) was found at surgery in 53% and
      88% of patients in the normal and positive MRI groups, respectively (P < 0.05).
      The early surgical success rate (combining patients with corticotropic deficiency
      and patients with eucortisolism) was similar in the normal and positive MRI
      groups (78% and 88%, respectively; P = 0.85). The recurrence rate was lower in
      the normal MRI group, but the difference did not reach statistical significance
      (9% vs. 30%; P = 0.07). The final remission rate at the last visit was similar in
      the normal and positive MRI groups (72% and 61%, respectively; P = 0.29).
      Postoperative complications were also similar: 10 patients (36%) with normal MRI
      and five patients (20%) with positive MRI had at least one postoperative
      complication (surgical and/or pituitary deficiency; P = 0.12). Thus, the outcome
      of pituitary surgery in CD appears to be similar regardless of whether pituitary
      MRI shows a microadenoma. We recommend neurosurgical pituitary exploration as the
      first-line treatment of CD, provided that the pituitary origin of ACTH secretion
      is confirmed by bilateral petrosal sinus sampling in patients with normal
      pituitary MRI findings.

PMID- 15240618
TI  - Lipid profile disorders induced by long-term cessation of physical activity in
      previously highly endurance-trained subjects.
AB  - The objective of this study was to describe long-term detraining effects on lipid
      profile in previously highly endurance-trained athletes. The study design was
      longitudinal, with a 2-yr follow-up study of changes in lipid profile during hard
      training and detraining. Ten subjects trained for 2 yr (22 h/wk; two 47-wk
      training periods with a 5-wk recovery period), and the 10 others stopped training
      after wk 47. Main blood lipid profile parameters, energy intake, and body
      composition were measured at baseline (wk 1) and at wk 24, 47, 52, 76, and 99.
      Although food caloric intake was reduced (2411 +/- 256 vs. 5697 +/- 455 kcal/d,
      detraining vs. training), detraining induced a decrease in high density
      lipoprotein cholesterol and increases in fat mass (by 6.5 +/- 1.1 kg), body mass
      index, leptin, low density lipoprotein cholesterol, low density lipoprotein/high
      density lipoprotein ratio, and apolipoprotein B, although insulin resistance
      (determined by homeostasis model assessment) stabilization had previously
      occurred. Further disorders appeared in triglycerides (TG) metabolism during
      detraining, with a persistent increase in TG (from 1.0 +/- 0.3 to 1.4 +/- 0.3
      mmol/liter), whereas glycerol decreased (from 88 +/- 9 to 73 +/- 8
      micromol/liter), and very low density lipoprotein-TG, chylomicrons, and
      apolipoprotein C(3) remained stable. Plasma lipoprotein lipase activity decreased
      whereas hepatic lipase activity remained stable. As well as a rapid loss of
      endurance-training benefits for the cholesterolemic profile, detraining also
      induced disorders in TG metabolism, possibly as a result of the elevated TG
      turnover acquired with long-term hard training.

PMID- 15240619
TI  - Calcium kinetics are altered in clinically stable girls with cystic fibrosis.
AB  - Reduced bone mass in individuals with cystic fibrosis (CF) may result from
      alterations in calcium metabolism. Bone calcium deposition and resorption rates,
      calcium balance, and markers of bone turnover were assessed using stable isotopes
      of calcium in 22 prepubertal and pubertal girls with CF. Bone calcium deposition
      was associated with the availability of dietary calcium, total serum osteocalcin,
      and leptin concentrations. Reduced bone mass in individuals with CF may result
      from inadequate bone calcium (Ca) deposition, and excessive resorption, although
      these parameters have not been directly assessed in children with CF. We used
      stable Ca isotopes to measure rates of bone Ca deposition (Vo+), resorption, and
      retention in 22 clinically stable girls with CF (aged 7-18 yr). Rates of bone Ca
      deposition were determined by mathematically modeling the disappearance of iv Ca
      stable isotope ((42)Ca) for 6 d post dosing. Indirect markers of bone turnover
      and hormones associated with pubertal development were also assessed. Rates of
      bone Ca deposition and retention were highest during early puberty (Tanner stages
      2 and 3). Calcium deposition rates in prepubertal (Tanner 1) and postmenarchal
      girls (Tanner stages 4 and 5) did not support substantial bone Ca retention. Net
      absorption of dietary Ca and serum osteocalcin and leptin concentrations were
      positively associated with Vo+. Time post menarche and serum leptin
      concentrations explained 91% of the variability in Vo+ (P = 0.0007). Serum total
      osteocalcin was low (10.9 +/- 5.4 ng/ml), and a substantial percentage of
      osteocalcin was undercarboxylated (54.3 +/- 11.8%). We concluded that increased
      calcium absorption and serum leptin concentrations were significantly associated
      with rates of bone Ca deposition, demonstrating an impact of nutritional status
      on this process. Rates of bone Ca deposition were lower than typically reported
      in healthy children, as were indirect markers of bone formation. These
      alterations in bone turnover contribute to reduced bone mass in girls with CF.

PMID- 15240620
TI  - Effect of multiple endocrine neoplasia type 1 (MEN1) gene mutations on premature
      mortality in familial MEN1 syndrome with founder mutations.
AB  - Estimation of mortality and the natural course of a disease is usually based on
      information of carefully studied individuals with or at risk for a specific
      disease. Genealogical information has rarely been accurate enough for such
      studies. With the help of church records and multiple endocrine neoplasia type 1
      (MEN1) family information of the two founder MEN1 mutations in Northern Finland
      (1466del12 and 1657insC), we could trace back common ancestors born in the
      beginning of the 1700s (1466del12) and approximately 1850 (1657insC) and find 67
      probable gene carriers born between 1728 and 1929, which were identified among
      their offspring. Information was gathered from 34 obligatory MEN1 gene carriers
      and 31 spouses. The mean age (+/- sd) of death of affected males (n = 16) was
      61.1 +/- 12.0 yr vs. 65.8 +/- 15.3 yr for unaffected males (n = 16) and for
      affected females (n = 16) was 67.2 +/- 10.7 yr vs. 67.7 +/- 14.7 yr for
      unaffected females (n = 13). The ages of death of the obligatory heterozygotes
      did not differ from that of the spouses in sex groups or from the sex-matched
      life expectancy estimates derived from Finnish national statistics. Causes of
      death differed significantly between female probands and spouses. In conclusion,
      obligatory MEN1 gene carrier status did not show a harmful effect on survival in
      this retrospective analysis tracing back to almost 300 yr.

PMID- 15240621
TI  - Body mass index determines evoked growth hormone (GH) responsiveness in normal
      healthy male subjects: diagnostic caveat for adult GH deficiency.
AB  - GH secretion is decreased in obese subjects, whereas age-adjusted IGF-I
      concentrations are normal. This study was undertaken to rigorously delineate the
      extent of obesity [elevated body mass index (BMI)] associated with decreased
      somatotrope secretory function resulting in apparent adult GH deficiency. The
      peak GH response evoked by combined arginine (0.5 g/kg infused iv over 30 min)
      and GHRH (1 microg/kg iv bolus) was measured in 59 healthy male subjects with
      BMIs ranging from normal to obese. BMI correlated with the peak evoked GH
      response (Pearson r = -0.59; P < 0.01), and the percentage of subjects exhibiting
      an abnormal evoked GH response, i.e. less than 9 ng/ml, increased from 5% for
      those with a BMI less than 25 (normal), to 13% for those with a BMI of 25-26.9
      (mildly overweight), to 33% for those with a BMI of 27-29.9 (moderately
      overweight), and to 64% for those with a BMI of 30 or more (obese). BMI is a
      major determinant of evoked adult GH response to provocative testing. The
      diagnosis of adult GH deficiency using the evoked GH response in patients with
      even mild BMI elevation does not accurately distinguish normal from deficient
      responses and may result in the erroneous classification of obese subjects as GH
      deficient and thus unnecessarily requiring GH replacement.

PMID- 15240622
TI  - Follow-up of low risk patients with papillary thyroid cancer: role of neck
      ultrasonography in detecting lymph node metastases.
AB  - Persistent or recurrent disease is rare in low risk patients with papillary
      thyroid cancer, and follow-up of these patients is a matter of debate. Neck
      ultrasonography (US), serum thyroglobulin (Tg), and whole body scan (WBS) after
      T(4) withdrawal were performed in 456 patients, followed up to 5 yr. At the end
      of the first year, 335 patients were Tg negative, and 121 were Tg positive; 65 of
      96 patients with Tg levels between 1 and 10 ng/ml became spontaneously Tg
      negative after 2 yr. During follow-up, WBS discovered node metastases in 13
      subjects, and US discovered node metastases in 38 subjects (31 Tg positive and 7
      Tg negative). WBS did not add any information, because all WBS-positive patients
      were also US and Tg positive. Fifty percent of metastases were less than 1 cm and
      not palpable. Finally, the negative predictive value of both negative Tg and US
      at first follow-up was 98.8%. We suggest a first follow-up based upon US
      assessment and stimulated (after T(4) withdrawal or recombinant human TSH) serum
      Tg determination; subsequently, 1) US should not be mandatory at each examination
      in initially Tg- and US-negative subjects, but is strongly suggested in all other
      cases; 2) Tg determination should be repeated 1 yr later, after exogenous or
      endogenous TSH stimulation only in initially Tg-positive patients without any
      other evidence of residual disease; and 3) Tg measurement during therapy should
      be sufficient in all other cases.

PMID- 15240623
TI  - Usefulness of homeostasis model assessment for identifying subjects at risk for
      hypoglycemia failure during the insulin hypoglycemia test.
AB  - One of the main problems of the insulin hypoglycemia test (IHT) is the failure to
      achieve an adequate hypoglycemia (blood glucose, <45 mg/dl) with the standard
      dose of insulin used. The aim of the study was to identify by means of
      homeostasis model assessment (HOMA) the subjects at risk for hypoglycemia failure
      during IHT. For this purpose 32 patients in whom an IHT was performed were
      prospectively included. Receiver operating characteristics curve analyses were
      performed to assess the sensitivity and specificity of both insulinemia and HOMA.
      Eight patients (25%) did not reach adequate hypoglycemia. A serum insulin
      concentration above 17.7 microIU/ml or a HOMA value above 4.38 identified those
      subjects who would not reach adequate hypoglycemia with a probability of 75%. By
      contrast, when the levels of either insulinemia or HOMA were lower than the cut
      off points mentioned above, the probability that individuals would reach
      sufficient hypoglycemia was 89.5%. In conclusion, quantitative estimate of
      insulin resistance by HOMA is a simple and reliable method that permits
      identification of individuals at risk of not reaching adequate hypoglycemia
      during IHT. In these patients, either alternative tests or a higher dose of
      insulin should be considered.

PMID- 15240624
TI  - Hormonal and biochemical normalization and tumor shrinkage induced by anti
      parathyroid hormone immunotherapy in a patient with metastatic parathyroid
      carcinoma.
AB  - Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, and the
      efficacy of medical therapy and chemo- and radiotherapy is poor in recurrent or
      metastatic disease. We report the first case of PTH immunization in which tumor
      shrinkage accompanied hormonal, biochemical, and clinical improvements in a
      patient with metastatic parathyroid carcinoma.A 50-yr-old woman with refractory
      parathyroid carcinoma and pulmonary metastases was immunized eight times between
      February 2001 and December 2003 with bovine and modified human PTH fragments and
      intact human PTH, mixed with Freund's adjuvant. Total and ionized calcium and PTH
      levels were assayed weekly for 6 months and regularly thereafter. Thoracic
      computed tomography scans were performed regularly. Antibodies to all PTH
      fragments were detected after two immunizations. Baseline PTH and total calcium
      were 213.0 ng/liter and 13.96 mg/dl, respectively, and remained elevated during
      the first three immunizations. From the fourth immunization onward, PTH and
      calcium decreased, and the patient's clinical condition improved markedly. PTH
      and calcium levels have remained controlled for more than 24 months, and the
      sizes (surface area) of pulmonary metastases decreased from baseline by 39-71%.
      This is the first evidence that PTH immunization not only can improve clinical,
      hormonal, and biochemical measures in parathyroid carcinoma but also has an
      antitumor effect.

PMID- 15240625
TI  - Sources of dietary iodine: bread, cows' milk, and infant formula in the Boston
      area.
AB  - Dietary iodine is essential for thyroid hormone production. Although U.S. dietary
      iodine is generally adequate, some groups, especially women of childbearing age,
      are at risk for mild iodine deficiency. Children's average urinary iodine is
      higher than that of adults. U.S. dietary iodine sources have not been assessed
      recently. A survey of iodine content in 20 brands of bread, 18 brands of cows'
      milk, and eight infant formulae was performed between 2001 and 2002. Three bread
      varieties contained more than 300 microg iodine per slice. Iodine content in
      other brands was far lower (mean +/- sd, 10.1 +/- 13.2 microg iodine/slice). All
      cows' milk samples had at least 88 microg iodine/250 ml, ranging from 88-168
      microg (116.0 +/- 22.1 microg/250 ml). Infant formulae values ranged from 16.2 to
      56.8 microg iodine/5 oz (23.5 +/- 13.78 microg/5 oz). The public should be aware
      of the need for adequate dietary iodine intake and should be aware that
      ingredient lists do not reflect the iodine content of foods.

PMID- 15240626
TI  - Ovarian hormone status and abdominal visceral adipose tissue metabolism.
AB  - We examined abdominal sc and visceral adipose tissue metabolism in a sample of 19
      regularly cycling premenopausal women (age 46.3 +/- 3.7 yr) and 10 women with
      natural menopause or pharmacological ovarian suppression (age 51.1 +/- 9.2 yr).
      Subcutaneous and visceral (omental, epiploic) adipose tissue biopsies were
      obtained during abdominal hysterectomies. Body composition and adipose tissue
      distribution were measured before the surgery by dual x-ray absorptiometry and
      computed tomography, respectively. Ovarian hormone-deficient women tended to be
      older (P = 0.08) and were characterized by increased visceral adipose tissue area
      (P < 0.05). Subcutaneous adipocyte size, lipoprotein lipase (LPL) activity, and
      basal lipolysis were not significantly different between groups. On the other
      hand, omental fat cell size was significantly higher in ovarian hormone-deficient
      women, compared with premenopausal women (P < 0.05). The omental/sc LPL activity
      ratio and omental adipocyte basal lipolysis were also significantly higher in
      ovarian hormone-deficient women (P < 0.05 for both comparisons). Significant
      positive correlations were found between visceral adipose tissue area and omental
      LPL activity (r = 0.54, P < 0.003), omental adipocyte basal lipolysis (r = 0.66,
      P < 0.0001), and omental fat cell size (r = 0.81, P < 0.0001). In multivariate
      analyses, ovarian status was no longer a significant predictor of adipose cell
      metabolism variables after visceral adipose tissue area was entered into the
      model, with the exception of the omental/sc LPL activity ratio, which remained
      independently associated with ovarian status. In conclusion, although the size of
      the visceral adipose tissue compartment was an important determinant of adipocyte
      metabolism in this depot, the increased omental/sc LPL activity ratio in ovarian
      hormone-deficient women supports the notion of a predominant visceral fat storage
      in these women.

PMID- 15240627
TI  - Effect of variations in small intestinal glucose delivery on plasma glucose,
      insulin, and incretin hormones in healthy subjects and type 2 diabetes.
AB  - The determinants of postprandial blood glycemia are controversial. We assessed
      the effects of variations in the initial rate of small intestinal glucose
      delivery on blood glucose, plasma insulin, and incretin responses in both health
      and type 2 diabetes. Eight controls and eight patients with type 2 diabetes
      managed by diet alone underwent paired studies. On both days subjects received an
      intraduodenal glucose infusion (t = 0-120 min); on one day the infusion rate was
      variable, being more rapid initially (3 kcal/min) between t = 0 and 15 min and
      slower (0.71 kcal/min) subsequently (t = 15-120 min), whereas on the other day,
      the infusion rate was constant (1 kcal/min) from t = 0 to 120 min (i.e. on both
      days 120 kcal of glucose were administered). Between t = 0-180 min blood glucose,
      plasma insulin and plasma glucose-dependent insulin-releasing polypeptide were
      greater with the variable, compared with the constant, infusion. Between t = 0
      and 30 min the magnitude of the rise in plasma glucagon-like peptide-1 was
      greater with the variable, compared with the constant infusion (P < 0.01, both
      groups). We conclude that modest variations in the initial rate of duodenal
      glucose entry may have profound effects on subsequent glycemic, insulin, and
      incretin responses.

PMID- 15240628
TI  - Type 1 diabetes-related antibodies in the fetal circulation: prevalence and
      influence on cord insulin and birth weight in offspring of mothers with type 1
      diabetes.
AB  - During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross
      the placenta. It is proposed that insulin antibodies (IA) allow transfer of
      insulin across the placenta, contributing to fetal hyperinsulinemia and
      macrosomia. We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and
      glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with
      type 1 diabetes (ODM, n = 138) and control mothers (control, n = 47) and further
      assessed cross-sectional relationships of antibody titers to birth weight and
      fetal insulin. In ODM, antibodies were frequently present in cord blood; 124 ODM
      (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61
      (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies
      were absent, whereas seven controls (15%) were positive for IA at low titers (P <
      0.0001 ODM vs. controls for all).ODM with IA (IA positive) or without IA (IA
      negative) had similar birth weights (mean +/- sd: IA positive, 3.8 +/- 0.7 kg; IA
      negative, 4.0 +/- 0.6 kg; P = 0.31) and cord insulin concentrations (IA positive:
      median, 112 pmol/liter; interquartile range, 62-219 pmol/liter; IA negative:
      median, 114 pmol/liter; interquartile range, 59-194 pmol/liter; P = 0.96).
      Similarly, the presence of GADA and/or IA-2 autoantibodies (n = 103) was not
      associated with differences in birth weight or insulin concentrations. Antibody
      titers were not associated with birth weight or insulin as continuous variables
      in either controls or ODM. Islet autoantibodies and IA are a common finding in
      cord blood of ODM, but we found no evidence that they influence offspring insulin
      concentrations or weight at birth.

PMID- 15240629
TI  - Cultured muscle cells from insulin-resistant type 2 diabetes patients have
      impaired insulin, but normal 5-amino-4-imidazolecarboxamide riboside-stimulated,
      glucose uptake.
AB  - Impaired insulin action is a characteristic feature of type 2 diabetes. The study
      aims were to investigate whether after prolonged culture skeletal muscle cultures
      from insulin-resistant, type 2 diabetic patients (taking >100 U insulin/d)
      displayed impaired insulin signaling effects compared with cultures from
      nondiabetic controls and to determine whether retained abnormalities were limited
      to insulin action by studying an alternative pathway of stimulated glucose
      uptake. Studies were performed on myotubes differentiated for 7 d between
      passages 4 and 6. Insulin-stimulated glucose uptake (100 nm; P < 0.05) and
      insulin-stimulated glycogen synthesis (1 nm; P < 0.01) were significantly
      impaired in the diabetic vs. control cultures. Protein kinase B (PKB) expression
      and phosphorylated PKB levels in response to insulin stimulation (20 nm) were
      comparable in the diabetic and control cultures. 5-Amino-4-imidazolecarboxamide
      riboside (AICAR) mimics the effect of exercise on glucose uptake by activating
      AMP-activated protein kinase. There was no difference in AICAR (2 mm)-stimulated
      glucose uptake between diabetic vs. control myotube cultures (P = not
      significant). In conclusion, diabetic muscle cultures retain signaling defects
      after prolonged culture that appear specific to the insulin signaling pathway,
      but not involving PKB. This supports an intrinsic abnormality of the diabetic
      muscle cells that is most likely to have a genetic basis.

PMID- 15240630
TI  - Dehydroepiandrosterone-sulfate inhibits nuclear factor-kappaB-dependent
      transcription in hepatocytes, possibly through antioxidant effect.
AB  - Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the representative sex
      steroid precursors, are postulated to have antiinflammatory effects, although the
      molecular background remains unknown. In this study, we examined the effects of
      these sex steroid precursors on cytokine-induced, nuclear factor-kappaB (NF
      kappaB)-mediated transcription. The HuH7 human hepatocyte cell line was stably
      transfected with an NF-kappaB-luciferase reporter gene or transiently transfected
      with other representative response elements-luciferase fusion genes, and the
      effects of DHEA/DHEAS on proinflammatory cytokine-induced transcription were
      estimated by luciferase assay. The results showed that DHEA/DHEAS potently
      inhibited TNF-alpha-induced NF-kappaB-dependent transcription in a time- and dose
      dependent manner. The effect was more obvious for DHEAS than for DHEA, and both
      steroids preferentially inhibited the cytokine-stimulated rather than basal NF
      kappaB-mediated transcription. Similar effects were observed in activator protein
      1-dependent but not constitutive Rous sarcoma virus promoter-dependent
      transcription. Two major downstream products of the sex steroid precursors,
      estradiol and testosterone, had no effect, indicating that the observed
      suppressive effect is not mediated by these metabolites. In contrast,
      glucocorticoids showed inhibitory effects on both basal and stimulated
      transcription and had an additive effect with DHEAS, suggesting the independent
      mechanisms of action of these steroid hormones. Finally, DHEAS eliminated
      hydroxyradical-induced activation of NF-kappaB-dependent transcription as well.
      Altogether, these results suggest that DHEA/DHEAS have an antiinflammatory effect
      in such a way that they inhibit proinflammatory cytokine-stimulated, NF-kappaB
      mediated transcription, at least partly through their antioxidant properties.

PMID- 15240631
TI  - Thyroid function and blood pressure homeostasis in euthyroid subjects.
AB  - Overt and subclinical hypothyroidism are associated with increased systemic
      vascular resistance and hypertension. We examined the relationship between
      thyroid function and blood pressure homeostasis in euthyroid individuals. A total
      of 284 subjects (68% hypertensive) consumed high- (200 mmol) and low- (10 mmol)
      sodium diets, and their blood pressure responses were assessed as percentage
      change in the mean arterial pressure (MAP). p-Aminohippuric acid clearance was
      used to estimate effective renal plasma flow. Renal vascular resistance (RVR) was
      calculated as MAP divided by effective renal plasma flow. Serum free T(4) index
      (FTI) was lower (P < 0.0001) and TSH was higher (P = 0.046) in hypertensive
      compared with normotensive subjects independent of other baseline
      characteristics. FTI (beta = -1.51, P < 0.0001), baseline MAP, and race
      independently predicted MAP salt sensitivity. The FTI relationship with salt
      sensitivity adjusted for baseline MAP and race was similar among normotensive
      (beta = -1.42, P = 0.008) and hypertensive subjects (beta = -1.66, P = 0.0001).
      FTI correlated negatively with high- (P = 0.0001) and low- (P = 0.008) salt RVR,
      whereas TSH correlated positively with high- (P = 0.016) and low- (P = 0.012)
      salt RVR independent of age, gender, race, and body mass index. We have found
      that FTI is lower and TSH is higher in hypertensive compared with normotensive
      euthyroid subjects and that FTI independently predicts blood pressure salt
      sensitivity. These data show that the influence of thyroid function on blood
      pressure homeostasis extends into euthyroid range and likely reflects the action
      of thyroid hormone on peripheral vasculature.

PMID- 15240632
TI  - Breast and uterine effects of soy isoflavones and conjugated equine estrogens in
      postmenopausal female monkeys.
AB  - In this study we evaluated the long-term effects of soy isoflavones on
      intermediate markers of cancer risk in the normal postmenopausal monkey breast
      and uterus. Ovariectomized female cynomolgus monkeys were randomized to receive
      one of three diets for 36 months: 1) isoflavone-depleted soy protein isolate (SPI
      ) (n = 57); 2) soy protein isolate with the equivalent of 129 mg/d isoflavones
      (SPI+) (n = 60); or 3) isoflavone-depleted soy protein isolate with conjugated
      equine estrogens at a dose scaled to approximate 0.625 mg/d in women (n = 62).
      End points included breast and uterine proliferation markers, sex steroid
      receptor expression, and serum estrogens. Epithelial proliferation and
      progesterone receptor expression in the breast and uterus were significantly
      higher in the conjugated equine estrogen group, compared with SPI+ and SPI-
      groups, whereas no significant differences were detected between the SPI+ and SPI
      groups. SPI+ treatment resulted in significantly lower serum concentrations of
      estrone (P < 0.01) and estradiol (P < 0.05) vs. SPI-. Within the SPI+ group,
      serum isoflavone concentrations were inversely correlated with serum estrone and
      mammary glandular area. These findings suggest that high dietary levels of soy
      isoflavones do not stimulate breast or uterine proliferation in postmenopausal
      monkeys and may contribute to an estrogen profile associated with reduced breast
      cancer risk.

PMID- 15240633
TI  - Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes.
AB  - Exendin-4 is a reptilian peptide that activates the mammalian receptor for
      truncated glucagon-like peptide 1 (tGLP-1) with relatively prolonged actions.
      Exendin-4 and tGLP-1 can reduce blood glucose levels by stimulating insulin
      secretion, inhibiting glucagon secretion, and delaying gastric emptying. We
      tested a range of doses of exendin-4 on postcibal glycemic excursions in nine
      volunteers with type 1 diabetes, all with negligible endogenous insulin
      secretion, in paired comparisons with vehicle in at least six volunteers with
      each of six doses. We established a side effect-free dose and an appropriate
      antecibal time for sc administration of exendin-4. Subsequently, exendin-4 was
      administered 15 min before breakfast, with usual insulin, to eight of the
      volunteers. Acetaminophen was ingested with the meal as an indicator of gastric
      emptying. The mean plasma glucose excursion was reduced by 90%, falling into the
      normal range, after breakfast, whereas plasma pancreatic polypeptide, glucagon,
      and acetaminophen levels were reduced, and insulin levels were not affected.
      Thus, normalization of postcibal glycemia was associated with delayed gastric
      emptying and suppression of glucagon secretion, without increased secretion or
      blood levels of insulin. We suggest that tGLP-1 agonists have therapeutic
      potential as congeners with insulin in C-peptide-negative type 1 diabetes.

PMID- 15240634
TI  - Polymorphisms in the cytotoxic T lymphocyte antigen-4 gene region confer
      susceptibility to Addison's disease.
AB  - The cytotoxic T lymphocyte antigen-4 (CTLA4) gene on chromosome 2q33 encodes a
      key regulator in the adaptive immune system. The CTLA4 surface molecule is
      expressed on activated T lymphocytes and involved in down-regulation of the
      immune response. Previous studies on a possible association between autoimmune
      Addison's disease and CTLA4 polymorphisms have shown conflicting results. A
      recent study identified new candidate polymorphisms in the CTLA4 region,
      influencing gene splicing and thereby the relative abundance of soluble CTLA4. We
      genotyped 134 patients with Addison's disease and 413 healthy controls from
      Norway and United Kingdom for these newly identified polymorphisms. Our data
      demonstrate that the same polymorphisms that have recently been demonstrated to
      confer susceptibility to autoimmune thyroid disease and type 1 diabetes also
      confer susceptibility to Addison's disease. This finding suggests that
      polymorphisms in CTLA4 confer general risk to develop autoimmunity and identifies
      a potential therapeutic target in the prevention of autoimmune endocrine
      disorders.

PMID- 15240635
TI  - Increased expression of the relaxin receptor (LGR7) in human endometrium during
      the secretory phase of the menstrual cycle.
AB  - Relaxin (RLX) is a structural homolog of insulin that is the ligand for the LGR7
      receptor. Although the 6k peptide is produced by the ovaries to cause connective
      tissue remodeling of the rodent and pig reproductive tracts to facilitate
      parturition, in human reproduction, the role of RLX is less well understood.
      Binding of human gene 2 (H2) [(33)P]-RLX, expression of RLX peptides and the LGR7
      receptor was examined in the human uterus at different stages of the menstrual
      cycle. A significant increase in RLX receptor binding in endometrium was
      identified by quantitative autoradiography in the secretory compared with the
      proliferative phase. H2RLX competed with [(33)P]-H2RLX binding with higher
      affinity than porcine RLX during both the proliferative and secretory phases.
      Increased LGR7 receptor gene expression during the secretory phase paralleled the
      changes in [(33)P]-H2RLX binding. Human gene 1 RLX transcripts were not detected
      in the uterus, and H2RLX gene expression was low and not influenced by the stage
      of the menstrual cycle. The studies show that binding to and gene expression of
      the LGR7 RLX receptor changes markedly with the phases of the menstrual cycle,
      suggesting a specific role for the hormone in the physiology of the human uterus.

PMID- 15240636
TI  - Hormonal and body composition predictors of soluble leptin receptor, leptin, and
      free leptin index in adolescent girls with anorexia nervosa and controls and
      relation to insulin sensitivity.
AB  - Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine
      secreted by adipose tissue and known to suppress appetite. Leptin may play a
      permissive role in onset of puberty and in resumption of gonadal function in
      conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main
      leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure
      of the free leptin index (FLI), which may be a more accurate determinant of
      leptin function. Determinants of sOB-R and FLI have not been examined in an
      adolescent population. We examined levels of sOB-R, leptin, and FLI, and body
      composition and hormonal determinants of these variables in 23 adolescent girls
      with AN and 21 healthy adolescent girls of comparable maturity prospectively over
      1 yr. Measures of insulin resistance and adiponectin were also examined. We
      determined changes in levels of sOB-R, leptin, and FLI with weight recovery
      (defined as an increase in body mass index of >/=10%, n = 11), and with
      resumption of menstrual cycles (n = 13). Girls with AN had significantly higher
      levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P
      < 0.0001 for both) than healthy controls, and levels of FLI were reduced more
      than levels of leptin in girls with AN compared with controls. An inverse
      correlation was noted between levels of leptin and sOB-R for the group as a whole
      (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most
      important predictor of levels of sOB-R was cortisol in the group as a whole (r =
      0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008).
      Other independent predictors of sOB-R levels for the entire group were percent
      body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The
      most important predictors of leptin and FLI were body mass index and percent body
      fat. An inverse relationship was noted between measures of insulin resistance and
      sOB-R levels, whereas a positive association was noted between these measures and
      leptin and FLI. Adiponectin values did not differ in girls with AN compared with
      healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight
      recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7
      to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0
      to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but
      not weight recovery alone, was associated with significant increases in FLI (0.19
      +/- 0.04 to 0.50 +/- 0.09 microg/U x 10(-3), P = 0.02).We demonstrate an increase
      in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and
      also demonstrate that cortisol is the most important predictor of levels of sOB-R
      in this condition. Levels of leptin and FLI, conversely, are primarily predicted
      by body composition. Weight recovery is associated with a decrease in sOB-R and
      an increase in leptin. Resumption of menses is associated with significant
      increases in the FLI, suggesting that free leptin may be an important determinant
      of menstrual recovery.

PMID- 15240637
TI  - Defective liver disposal of free fatty acids in patients with impaired glucose
      tolerance.
AB  - The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one
      main site of their reciprocal regulation. Acute exposure to hyperglycemia and
      hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy
      humans. We investigated whether a spontaneous condition of chronic mild
      hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx
      rate constant (LKi) was measured after a 12-15-h fast in 10 patients with
      impaired glucose tolerance (IGT) and eight control subjects using positron
      emission tomography in combination with the long-chain FFA analog 14(R,S)
      [18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had
      higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/
      0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs.
      1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs.
      0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced
      in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014
      min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51,
      P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels
      (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver
      to extract FFA from the circulation appears to be impaired. The reciprocal
      relationship between hepatic FFA extraction and glucose/lactate flux may derive
      from intrahepatic substrate competition.

PMID- 15240638
TI  - Antiproliferative effects of Src inhibition on medullary thyroid cancer.
AB  - There is no effective treatment for recurrent or metastatic medullary thyroid
      cancer (MTC). Hereditary MTC is associated with mutations in the RET
      protooncogene, which encodes for a tyrosine kinase. We postulated that Src
      tyrosine kinases regulate MTC proliferation. Proliferation of the human MTC cell
      line, TT, was examined in the presence of a Src-specific tyrosine kinase
      inhibitor, PP2, or genistein. Cell counts were performed with a Coulter counter
      or by flow cytometry. DNA synthesis was evaluated by bromodeoxyuridine
      incorporation. A cell death ELISA was used to assess apoptosis. Akt
      phosphorylation was determined by Western immunoblot. MAPK activity was measured
      using an immunoprecipitation kinase assay, and MAPK inhibition was achieved with
      SB202190 (p38 MAPK) and PD098059 (MAPK kinase). Data were analyzed by ANOVA.
      Compared with controls, PP2 reduced DNA synthesis, abolished Akt phosphorylation,
      and increased apoptosis. The MAPK kinase inhibitor, PD098059, attenuated DNA
      synthesis, whereas genistein caused modest declines in cell count and DNA
      synthesis and minimal changes in apoptosis. We conclude that Src-dependent MTC
      proliferation occurs via increased DNA synthesis and reduced apoptosis. The
      latter effect may be mediated by Akt survival signals. Modulation of Src activity
      is a potential therapeutic target in MTC.

PMID- 15240639
TI  - Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-alpha
      and -beta, independent of ligand binding.
AB  - We studied the estrogenic activity of a component of Panax ginseng, ginsenoside
      Rb1. The activity of ginsenoside-Rb1 was characterized in a transient
      transfection system, using estrogen receptor isoforms and estrogen-responsive
      luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both
      alpha and beta estrogen receptors in a dose-dependent manner with maximal
      activity observed at 100 microm, the highest concentration examined. Activation
      was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that
      the effects were mediated through the estrogen receptor. Treatment with 17beta
      estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor,
      pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in
      COS cells. Although these data suggest that it is functionally very similar to
      17beta-estradiol, ginsenoside-Rb1 failed to displace specific binding of
      [(3)H]17beta-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding
      assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1
      is independent of direct estrogen receptor association.

PMID- 15240640
TI  - Impaired insulin secretion in the Turner metabolic syndrome.
AB  - An increased prevalence of impaired glucose homeostasis (IGH) and diabetes
      mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether
      IGH is an intrinsic feature of this syndrome, independent of obesity or
      hypogonadism, we compared results of a standard oral glucose challenge in age-
      and body mass index-matched women with TS and with karyotypically normal
      premature ovarian failure (POF). Fasting glucose levels were normal in both
      groups, but glucose values after oral glucose challenge were higher in TS [2-h
      glucose, 135 +/- 36 mg/dl (7.5 +/- 2.0 mmol/liter) in TS and 97 +/- 18 mg/dl (5.4
      +/- 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was
      lower in TS; e.g. the initial insulin response (DeltaI/DeltaG(30)) was decreased
      by 60% compared with POF (P < 0.0001). We also compared responses to a standard
      iv glucose tolerance test in women with TS and in age- and body mass index
      matched normal women and found that the insulin area under the curve was 50%
      lower in women with TS (P = 0.003). Insulin sensitivity measured by the
      quantitative insulin sensitivity check index was higher in women with TS compared
      with both control groups. Thus, IGH is not secondary to obesity or hypogonadism
      in TS, but it is a distinct entity characterized by decreased insulin secretion,
      suggesting that haploinsufficiency for X-chromosome gene(s) impairs beta-cell
      function and predisposes to diabetes mellitus in TS.

PMID- 15240641
TI  - A novel point mutation of the RET protooncogene involving the second
      intracellular tyrosine kinase domain in a family with medullary thyroid
      carcinoma.
AB  - Hereditary medullary thyroid carcinoma, a tumor that arises from the
      parafollicular cells of the thyroid gland, occurs in isolation (as in familial
      medullary thyroid carcinoma), in association with hyperparathyroidism and
      pheochromocytoma (as in multiple endocrine neoplasia type 2A), or in association
      with pheochromocytoma, marfanoid habitus, and mucosal neuromas (as in multiple
      endocrine neoplasia type 2B). These genetic syndromes are associated with
      germline-activating mutations of the RET protooncogene, a cell surface tyrosine
      kinase receptor, which is believed to modulate specific intracellular signaling
      pathways involved in the regulation of C cell proliferation and apoptosis. RET
      activating mutations involve two important functional areas of the receptor: the
      cysteine-rich extracellular domain and the intracellular tyrosine kinase domain.
      Multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma are
      more commonly associated with mutations in the cysteine-rich extracellular
      domain, whereas multiple endocrine neoplasia type 2B is exclusively associated
      with mutations involving the second intracellular tyrosine kinase domain. Here,
      we describe a novel missense mutation of the RET protooncogene that substitutes
      arginine for proline at codon 912 of the intracellular tyrosine kinase domain in
      a family with medullary thyroid carcinoma.

PMID- 15240642
TI  - Estrogen to antiestrogen with a single methylene group resulting in an unusual
      steroidal selective estrogen receptor modulator.
AB  - Selective estrogen receptor (ER) modulators (SERMs) are important therapeutic
      agents for breast cancer prevention and treatment. We have synthesized two
      analogs, E11-2,1 [methyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta
      yl)acetate] and E11-2,2 [ethyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta
      yl)acetate], the methyl and ethyl esters of an estradiol analog, substituted in
      the B ring at C-11beta with a carboxymethyl group. The shorter methyl ester, E11
      2,1, has high ER affinity and high estrogenic potency in the Ishikawa estrogen
      cell bioassay, whereas the longer ethyl ester, E11-2,2, has even higher ER
      affinity, but little or no estrogenic activity. We found that this minor change
      of one methylene group transforms a potent estrogenic agonist into an antagonist
      in vitro with either ER alpha or beta. In the rat, E11-2,2 acts as a SERM in the
      uterus, where it inhibits estradiol-induced proliferation, and as an estrogen
      agonist in the liver and skeleton, where it decreases plasma cholesterol and
      increases bone growth. The characteristic feature of antiestrogens, including
      SERMs, is a long and polar side-chain that prevents agonist-induced conformation
      of helix 12 of ER. E11-2,2 with its short, nonpolar side-chain, lacks this
      critical structure, presenting the possibility that it might act through a unique
      mechanism.

PMID- 15240643
TI  - Fasting ghrelin levels in physically active women: relationship with menstrual
      disturbances and metabolic hormones.
AB  - Recent findings support a role for ghrelin in the regulation of energy
      homeostasis and possibly reproductive function. The primary purpose of this study
      was to test whether differences in fasting ghrelin levels exist in exercising
      women with differing menstrual and metabolic status. Menstrual cycle status was
      defined as sedentary ovulatory (SedOvul; n = 10, cycles = 26), exercising
      ovulatory (ExOvul; n = 11, cycles = 22), exercising luteal phase
      defect/anovulatory (ExLPD/Anov; n = 11, cycle = 27), and exercising amenorrheic
      (ExAmen; n = 8, cycle = 16). Subjects were 27.7 +/- 1.2 yr of age, weighed 60.2
      +/- 3.3 kg, and had menstrual cycle lengths of 28.4 +/- 0.9 d. Blood was
      collected during the follicular phase (d 2-9) of each menstrual cycle and
      analyzed for total ghrelin, insulin, total T(3), and leptin. Ghrelin was
      significantly elevated by approximately 85% in the ExAmen category (725.5 +/-
      40.8 pmol/liter) when compared with all other categories (P < 0.001; SedOvul =
      393.6 +/- 32.0 pmol/liter, ExOvul = 418.9 +/- 34.8 pmol/liter, and ExLPD/Anov =
      381.1 +/- 314 pmol/liter). Leptin levels were lower in all groups vs. SedOvul (P
      < 0.001). Insulin was lower in both the ExLPD/Anov and ExAmen categories vs.
      SedOvul and ExOvul (P < 0.018), and total T(3) was lower in ExAmen compared with
      all other groups (P < 0.001), with concentrations in ExLPD/Anov and ExOvul
      exceeding those in SedOvul (P < 0.05). These data clearly indicate a metabolic
      hormonal profile consistent with chronic energy deficiency in exercising women
      across a range in menstrual status and introduces ghrelin as a potential
      supplementary indicator that uniquely discriminates amenorrheic athletes from
      athletes with other menstrual disturbances.

PMID- 15240644
TI  - Insulin-like growth factor-I stimulates both cell growth and lipogenesis during
      differentiation of human mesenchymal stem cells into adipocytes.
AB  - Insulin is known to regulate adipocyte differentiation and lipid accumulation,
      but the specific mechanism by which precursor cells differentiate into adipocytes
      is not clearly understood. This study evaluated the role of the IGF-I receptor in
      the process of adipocyte differentiation in bone marrow-derived human mesenchymal
      stem cells (HMSCs). The results demonstrated that nanomolar concentrations of IGF
      I adequately replaced micromolar concentrations of insulin in supporting
      differentiation and lipid accumulation in HMSCs. The addition of IGF-I
      specifically increased cell proliferation and lipid accumulation in HMSCs, but a
      mixture of differentiation factors including dexamethasone, indomethacin, and 3
      isobutyl-1-methylxanthine did not. These effects were blocked by the alphaIR-3
      antibody, which inhibits IGF-I receptor activity. We also describe the pattern of
      differentiation with regard to cell growth, lipid accumulation, and morphologic
      changes and define the changes in these parameters that are influenced by IGF-I.
      Finally, peroxisome proliferator activating receptor-gamma immunoreactivity was
      also increased in response to IGF-I, and this effect was blocked in cells treated
      with the alphaIR-3 antibody. Taken together, these findings suggest that IGF-I
      plays a critical role in adipocyte differentiation and lipid accumulation.

PMID- 15240645
TI  - Markedly diminished lipolysis and partial restoration of glucose metabolism,
      without changes in fat distribution after extended discontinuation of protease
      inhibitors in severe lipodystrophic human immunodeficient virus-1-infected
      patients.
AB  - Treatment for HIV-1 infection is often complicated by a lipodystrophy syndrome
      associated with insulin resistance and an elevated rate of lipolysis. In eight
      HIV-1 infected men with lipodystrophy syndrome, we studied the effects of
      replacement of protease inhibitor (PI) by abacavir on insulin sensitivity and
      lipolysis by hyperinsulinemic euglycemic clamp and on fat distribution assessed
      by dual-energy x-ray absorptiometry and computed tomography scan. Glucose
      metabolism and lipolysis were assessed by tracer dilution employing [6,6
      (2)H(2)]glucose and [(2)H(5)]glycerol, respectively. Data are expressed as mean
      +/- sd or 95% confidence interval (CI), as appropriate. There were no significant
      changes in fat distribution assessed by dual-energy x-ray absorptiometry and
      computed tomography scan at wk 36 and wk 96. The fasting total glucose production
      decreased from 16.1 +/- 2.5 at study entry by 1.1 (range, -2.1 to -0.1) to 15.0
      +/- 1.5 micromol/kg.min after PI withdrawal at wk 36 (n = 8). In an analysis
      restricted to the patients on treatment at wk 96 (n = 6), the decrease was 0.9
      (range, -2.1 to 0.3) micromol/kg.min. During insulin infusion, glucose oxidation
      (as percent of total glucose disposal) increased from 36.8 +/- 12.7% by 11.0%
      (range, 1.3-20.8) to 47.9 +/- 13.9% in the wk 36 analysis. In the analysis
      restricted to the patients on treatment at wk 96 (n = 6) the increase was 7.7 (
      4.0 to 19.4)%. Fasting lipolysis decreased from 2.7 +/- 0.6 micromol/kg.min by
      0.9 (-1.6 to -0.2) to 1.8 +/- 0.3 micromol/kg.min in the wk-96 analysis (n = 6).
      The replacement of the studied PIs by abacavir in severe lipodystrophic HIV-1
      infected patients results in a marked reduction of lipolysis. In contrast,
      fasting glucose production and insulin-stimulated glucose oxidation improve
      moderately, whereas insulin-stimulated glucose disposal and fat distribution do
      not change.

PMID- 15240646
TI  - Insulin and messenger ribonucleic acid expression of insulin receptor isoforms in
      ovarian follicles from nonhirsute ovulatory women and polycystic ovary syndrome
      patients.
AB  - Insulin action is mediated by two insulin receptor (IR) isoforms, differing in
      mitogenic and metabolic function. IR isoform expression might occur in human
      granulosa cells and could be altered in polycystic ovary syndrome (PCOS) from
      hyperinsulinemia. To determine the relationship between granulosa cell IR isoform
      expression and follicular fluid insulin concentration in individual follicles, 18
      normal women and seven PCOS patients receiving gonadotropins for in vitro
      fertilization were studied. Glucose tolerance testing was performed before
      pituitary desensitization, and fasting serum insulin was measured at oocyte
      retrieval. Granulosa cells and fluid aspirated from the first follicle were used
      to determine IR isoform mRNA expression and insulin concentration, respectively.
      IR isoform A mRNA expression was greater than that of IR isoform B expression in
      normal mural granulosa and cumulus cells, without a cell type effect.
      Intrafollicular insulin levels increased with adiposity and serum insulin levels
      at oocyte-retrieval but did not predict IR mRNA expression. Total IR mRNA
      expression, but not intrafollicular insulin levels, was elevated in PCOS
      patients, whereas intrafollicular insulin levels were increased in women with
      impaired glucose tolerance. Granulosa cell IR heterogeneity, together with
      adiposity-dependent intrafollicular insulin availability, introduces a novel
      mechanism by which insulin may affect granulosa cell function within the
      follicle.

PMID- 15240647
TI  - Effects of isolated isoflavonoids on lipids, lipoproteins, insulin sensitivity,
      and ghrelin in postmenopausal women.
AB  - The low cardiovascular risk in Asian women has been thought to result from high
      isoflavonoid intake. In a double-blind, randomized, placebo-controlled trial, we
      studied the effects of isolated isoflavonoids (114 mg/d) on lipids, lipoproteins,
      insulin sensitivity, and ghrelin in 56 nondiabetic postmenopausal women with a
      history of breast cancer. Isoflavonoid or placebo tablets were given for 3
      months, and the treatment regimens crossed over after a 2-month washout period.
      The concentrations of total cholesterol, high- and low-density lipoprotein
      cholesterol, triglycerides, apolipoproteins B and A1, and lipoprotein (a) were
      not affected by isoflavonoids. However, during the isoflavonoid regimen, women
      with low-density lipoprotein cholesterol level above the median (4.20 mmol/liter)
      showed a rise [0.65 +/- 0.60 (sd) mmol/liter], which was statistically different
      from the fall during the placebo regimen (-0.45 +/- 0.67 mmol/liter, P = 0.009).
      Isoflavonoids did not affect insulin sensitivity as assessed by an oral 2-h
      glucose tolerance test (75 g). Changes in ghrelin levels differed (P = 0.048)
      during the isoflavonoid (-7.1 +/- 151 micromol/liter) and placebo regimens (+47.9
      +/- 198 micromol/liter). In conclusion, we found no effects of isolated
      isoflavonoids on lipids, lipoproteins, or insulin sensitivity in postmenopausal
      women, implying no vascular benefit. Isoflavonoids may reduce ghrelin levels and
      thus hunger and weight.

PMID- 15240649
TI  - RET exon 11 (G691S) polymorphism is significantly more frequent in sporadic
      medullary thyroid carcinoma than in the general population.
AB  - The RET protooncogene is constitutively activated by point mutations in
      hereditary medullary thyroid carcinomas (MTCs). RET somatic point mutations have
      also been reported in 40-50% of sporadic MTCs. Several single nucleotide
      polymorphisms of the RET gene have been described in the general population as
      well as in patients with MTC. These allelic variants do not seem to confer any
      transforming activity to the tyrosine kinase domain of the RET gene. Because the
      exon 11 RET polymorphism determines an important aminoacidic variation (G691S),
      we studied its frequency in 212 subjects, 106 sporadic MTC patients and 106
      normal age-, sex-, race-, and geographic origin-matched controls. In 46 cases of
      sporadic MTCs, we also studied the cosegregation of somatic RET gene mutation and
      G691S polymorphism as well as the linkage of the polymorphism with RET germline
      mutation in 60 members of eight multiple endocrine neoplasia type 2 families. The
      influence of this polymorphism on the RET gene transcription has also been
      studied. In parallel we analyzed the frequencies of another three neutral
      polymorphisms (L769L, S836S, S904S). We found a statistically significant (P =
      0.029) higher allelic frequency of G691S polymorphism in MTCs (27.83%) than that
      found in normal controls (18.86%), at variance with the three neutral
      polymorphisms whose frequencies were not different in patients and controls. With
      this study we excluded the influence of the G691S polymorphism on RET mRNA
      expression, the development of the somatic RET mutation, the linkage with the
      germline RET mutation, the younger onset of the MTCs, and the clinical outcome of
      the disease. A putative role of the G691S polymorphism as genetic modifier in the
      normal subjects remains to be established.

PMID- 15240648
TI  - High energy flux mediates the tonically augmented beta-adrenergic support of
      resting metabolic rate in habitually exercising older adults.
AB  - The sympathetic nervous system contributes to resting metabolic rate (RMR) via
      beta-adrenergic receptor (beta-AR) stimulation of energy metabolism. RMR and beta
      AR support of RMR are greater in habitually exercising compared with sedentary
      older adults possibly due to greater energy flux (magnitude of energy intake and
      energy expenditure during energy balance). In 10 older adults regularly
      performing aerobic endurance exercise (mean +/- se, 66 +/- 1 yr) compared with
      baseline, a reduction in energy flux (via abstention of exercise and proportional
      reduction in dietary intake) decreased (P < 0.05) energy expenditure (7746 +/-
      440 vs. 9630 +/- 662 kJ.d(-1)), caloric intake (7808 +/- 431 vs. 9433 +/- 528
      kJ.d(-1)), RMR (5192 +/- 167 vs. 5401 +/- 209 kJ.d(-1)), and skeletal muscle
      sympathetic nervous system activity (36 +/- 2 vs. 42 +/- 2 bursts.min(-1)).
      Significant beta-AR support of RMR was observed at baseline (167 +/- 42 kJ.d(-1))
      but not during reduced energy flux. The change in RMR from baseline to reduced
      energy flux was related to the corresponding change in beta-AR support of RMR (r
      = 0.77, P = 0.009). No changes were observed in seven time controls (69 +/- 3 yr)
      who maintained energy flux. High energy flux is a key mechanism contributing to
      the elevated RMR and beta-AR support of RMR in habitually exercising older
      adults. Maintenance of high energy flux via regular exercise may be an effective
      strategy for maintaining energy expenditure and preventing age-associated
      obesity.

PMID- 15240650
TI  - Repression of oxidant-induced nuclear factor-kappaB activity mediates placental
      cytokine responses in gestational diabetes.
AB  - Although oxidative stress has been implicated in the pathogenesis of type 2
      diabetes, limited data are available regarding its role in gestational diabetes
      mellitus (GDM), a disease of similar pathophysiology. The proinflammatory
      cytokines TNFalpha, IL-6, and IL-8 are released from the placenta at term and
      have been implicated in and/or associated with various metabolic events,
      including decreased insulin sensitivity. Previously we reported differences in
      the ex situ release of proinflammatory cytokines from placental and adipose
      tissues obtained from women with and without GDM. We proposed that these
      differences reflect preexposure and/or adaptation to oxidative stress by GDM
      tissues. In this study, we tested the hypothesis that placental tissue from women
      with GDM is less responsive to oxidative stress than tissue from normal women.
      Under basal conditions, release of TNFalpha, IL-6, and IL-8 was similar in both
      control and GDM groups. However, 8-isoprostane release was 2-fold greater in the
      GDM group (P < 0.01). In response to oxidative stress, TNFalpha and 8-isoprostane
      release and nuclear factor-kappaB (NF-kappaB) DNA-binding activity were
      significantly increased in normal tissues (20-fold, 2-fold, and 35%,
      respectively, P < 0.01). In contrast, the response of GDM tissues to oxidant
      stress was blunted, with no change in 8-isoprostane release, a 4-fold increase in
      TNFalpha release, and a 40% reduction in NF-kappaB DNA-binding activity. These
      data support the hypothesis that placentae from women with GDM display a reduced
      capacity, mediated by repression of NF-kappaB activity, to respond to oxidative
      stress.

PMID- 15240651
TI  - A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and
      skeletal abnormalities is caused by a novel activating parathyroid hormone
      (PTH)/PTH-related peptide receptor mutation.
AB  - A novel heterozygous PTH/PTHrP receptor missense mutation (T410R) was identified
      in a male and his two sons who are all affected by a less severe form of Jansen's
      metaphyseal chondrodysplasia (JMC). JMC is a rare disorder that is typically
      characterized by severe growth plate abnormalities that lead to short-limbed
      dwarfism. Furthermore, affected individuals usually show significant
      hypercalcemia, despite normal or undetectable levels of PTH and PTHrP. In
      contrast, the three affected members of this new family showed only mild skeletal
      dysplasia, comparatively normal stature, and blood calcium concentrations either
      within or at the upper end of the normal range. However, PTH levels were
      suppressed, and urinary calcium excretion was elevated, which led to
      nephrolithiasis in both children. When expressed in COS-7 cells, the PTH/PTHrP
      receptor with the T410R mutation led to agonist-independent cAMP formation, which
      was less pronounced than that observed with the previously identified T410P
      mutant. Our findings indicate that a mild form of JMC has been identified that is
      characterized by less pronounced skeletal and laboratory abnormalities.

PMID- 15240652
TI  - Variation in the calpain-10 gene is associated with elevated triglyceride levels
      and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish
      subjects.
AB  - Our aim was to investigate the possible role of the type 2 diabetes
      susceptibility gene CAPN10 in obesity. A case control study consisting of 235
      obese Swedish subjects [body mass index, 40 (35-45) kg/m(2)] and 235 controls
      matched for age and gender [body mass index, 22 (21-24) kg/m(2)], and a
      transmission disequilibrium test consisting of 116 parents-offspring trios, where
      the offspring was abdominally obese [waist, 100 (95-110) cm], were performed.
      CAPN10 mRNA expression was studied in adipose tissue biopsies from 33 of the
      obese subjects participating in the case control study. The CAPN10 single
      nucleotide polymorphism (SNP)-43 was genotyped using PCR followed by NdeI
      digestion or by allelic discrimination. CAPN10 mRNA levels were quantified using
      real-time RT-PCR with Cyclophilin A as an internal standard. No significant
      associations between CAPN10 SNP-43 and obesity were seen, neither in the case
      control study nor in the transmission disequilibrium test, but obese subjects
      homozygous for the SNP-43 G allele had significantly elevated triglyceride levels
      compared with subjects carrying the A allele [1.7 (1.1-2.4) vs. 1.4 (1.0-2.0); P
      = 0.03]. The CAPN10 mRNA expression in sc fat was significantly reduced in
      subjects with the SNP-43 G/G genotype compared with carriers of SNP-43 G/A (G/G,
      0.33 +/- 0.02, vs. G/A, 0.51 +/- 0.09; P = 0.048), and a similar trend was
      observed in visceral fat (G/G, 0.52 +/- 0.06, vs. G/A, 0.65 +/- 0.10; P = 0.22).
      Our data suggest that reduced CAPN10 expression may be a risk factor for features
      associated with the metabolic syndrome in obese subjects, although variation in
      the gene does not seem to contribute to the risk for developing obesity per se.

PMID- 15240653
TI  - Impaired endothelial function in never-treated hypertensive subjects carrying the
      Arg972 polymorphism in the insulin receptor substrate-1 gene.
AB  - Some cardiovascular risk factors, such as hypertension and insulin resistance,
      are associated with endothelial dysfunction. Insulin regulates both in vitro and
      in vivo expression of endothelial nitric oxide synthase (eNOS) via a pathway
      involving insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3 kinase.
      Recently, we found that human endothelial cells obtained from carriers of the
      Arg(972) IRS-1 polymorphism exhibited reduced eNOS expression in response to
      chronic exposure to insulin. A reduction in eNOS expression would be expected to
      be associated with impaired endothelium-dependent vasodilation. To investigate a
      possible relationship between Arg(972) IRS-1 polymorphism and endothelial
      dysfunction in vivo, we enrolled a cohort of 100 never-treated hypertensive
      subjects. Endothelium-dependent and endothelium-independent vasodilation were
      assessed by increasing doses of acetylcholine and sodium nitroprusside. IRS-1
      polymorphism was detected by PCR. The allelic frequency of the Arg(972) IRS-1
      variant was 8.0%. Stratifying subjects according to IRS-1 genotype, we observed
      that acetylcholine-stimulated forearm blood flow was significantly (P < 0.0001)
      lower in Gly/Arg heterozygous carriers than in Gly/Gly carriers (11.3 +/- 4.4 vs.
      14.7 +/- 5.9 ml/100 ml(-1) of tissue per min(-1)). Sodium nitroprusside caused
      comparable increments in forearm blood flow in both groups (12.9 +/- 2.4 vs. 13.3
      +/- 3.5 ml/100 ml(-1) of tissue per min(-1)). Our data strongly suggest that, by
      inducing endothelial dysfunction, the Arg(972) IRS-1 polymorphism may contribute
      to the genetic predisposition to develop cardiovascular disease.

PMID- 15240654
TI  - Adaptation of human pineal melatonin suppression by recent photic history.
AB  - The human circadian pacemaker controls the timing of the release of the pineal
      hormone melatonin, which promotes sleep, decreases body temperature, and
      diminishes cognitive performance. Abnormal melatonin secretion has been observed
      in psychiatric and circadian disorders. Although melatonin secretion is directly
      suppressed by exposure to light in a nonlinear intensity-dependent fashion,
      little research has focused on the effect of prior photic history on this
      response. We examined eight subjects in controlled laboratory conditions using a
      within-subjects design. Baseline melatonin secretion was monitored under constant
      routine conditions and compared with two additional constant routines with a
      fixed light stimulus for 6.5 h of 200 lux (50 microW/cm(2)) after approximately 3
      d of photic exposure during the subjective day of either about 200 lux (50
      microW/cm(2)) or about 0.5 lux (0.15 microW/cm(2)). We found a significant
      increase in melatonin suppression during the stimulus after a prior photic
      history of approximately 0.5 lux compared with approximately 200 lux, revealing
      that humans exhibit adaptation of circadian photoreception. Such adaptation
      indicates that translation of a photic stimulus into drive on the human circadian
      pacemaker involves more complex temporal dynamics than previously recognized.
      Further elucidation of these properties could prove useful in potentiating light
      therapies for circadian and affective disorders.

PMID- 15240655
TI  - Understanding the pro- and anti-inflammatory properties of IL-27.
AB  - The recent identification of IL-27 (IL-27p28/EBV-induced gene 3) and IL-27R (WSX
      1/gp130) has provided new insights for the biology of IL-6/IL-12 family
      cytokines. Initial studies indicated that IL-27 can directly regulate T cell
      functions and suggested an important role for it in promoting Th1 type responses.
      However, subsequent studies have revealed that IL-27R signaling influences a
      variety of immune cell types and can inhibit either Th1 or Th2 type responses.
      Though elucidation of the Jak/STAT signaling pathways activated by IL-27R
      ligation has unveiled some of the molecular mechanisms used by IL-27 to promote
      inflammation, little is known about the anti-inflammatory activities of this
      cytokine. Thus, the aim of this review is to discuss the pleotropic nature of the
      IL-27/IL-27R interaction and attempt to reconcile the pro- and anti-inflammatory
      properties of this immunomodulator.

PMID- 15240656
TI  - Cutting edge: pulmonary immunopathology mediated by antigen-specific expression
      of TNF-alpha by antiviral CD8+ T cells.
AB  - Respiratory virus infection results in considerable pulmonary immunopathology, a
      component of which results from the host immune responses. We have developed a
      murine model to specifically examine the lung injury due to CD8(+) T cell
      recognition of an influenza hemagglutinin (HA) transgene on lung epithelium in
      the absence of replicating virus, after adoptive transfer. Lung injury is largely
      mediated by chemokines expressed by the epithelial cells upon T cell recognition
      mediated by TNF-alpha. To determine the critical source of TNF-alpha, HA-specific
      TNF(-/-) CD8(+) T cells were transferred into HA transgenic animals, and lung
      injury was not observed, though these T cells exhibited no defect in antiviral
      activity in vivo. This indicates that the initiating event in the injury process
      is Ag-specific expression of TNF-alpha by antiviral CD8(+) T cells upon
      recognition of alveolar epithelial Ag, and that the effector activities
      responsible for viral clearance may be dissociable from those resulting in
      immunopathology.

PMID- 15240657
TI  - Cutting edge: selective requirement for the Wiskott-Aldrich syndrome protein in
      cytokine, but not chemokine, secretion by CD4+ T cells.
AB  - The mechanism of cytokine secretion is not well understood, but cytokines appear
      to be synthesized and released in a polarized fashion toward an Ag-specific
      target cell. In this study, we demonstrate that the Wiskott-Aldrich syndrome
      protein (WASp) is an essential component of the cytokine secretory pathway in
      CD4(+) T cells. Murine WASp-deficient CD4(+) T cells fail to polarize cytokines
      toward a target and show an unexpected and striking block in cytokine secretion.
      In contrast, chemokine secretion and trafficking of plasma membrane proteins,
      transported via the constitutive secretory pathway, are unaffected by the lack of
      WASp. These results suggest that CD4(+) T cell cytokines require a specialized,
      WASp-dependent pathway for cellular traffic and/or vesicle release that is
      distinct from that required for chemokine release. We propose that the use of
      different secretory pathways for cytokines and chemokines enables CD4(+) T cell
      activity to be further fine-tuned to serve specialized effector functions.

PMID- 15240658
TI  - Cutting edge: induction of the antigen-processing enzyme IFN-gamma-inducible
      lysosomal thiol reductase in melanoma cells Is STAT1-dependent but CIITA
      independent.
AB  - Presentation and CD4(+) T cell responses to Ag in the context of MHC class II
      molecules require processing of native proteins into short peptide fragments.
      Within this pathway, IFN-gamma-inducible lysosomal thiol reductase (GILT)
      functions to catalyze thiol bond reduction, thus unfolding native protein Ag and
      facilitating further processing via cellular proteases. In contrast with
      professional APCs such as B cells, class II-positive human melanomas expressed
      relatively little to no GILT protein or mRNA. Tumor cell GILT expression was
      partially restored with IFN-gamma treatment but unlike other genes required for
      class II Ag presentation, GILT was not regulated by CIITA. Rather, studies
      revealed STAT1 plays a direct role in IFN-gamma-inducible GILT expression. These
      results define a molecular mechanism for the uncoupled regulation of MHC class II
      genes and the processing enzyme GILT in human melanomas.

PMID- 15240659
TI  - Cell proliferation and STAT6 pathways are negatively regulated in T cells by
      STAT1 and suppressors of cytokine signaling.
AB  - Suppressor of cytokine signaling (SOCS) proteins have emerged as important
      regulators of cytokine signals in lymphocytes. In this study, we have
      investigated regulation of SOCS expression and their role in Th cell growth and
      differentiation. We show that SOCS genes are constitutively expressed in naive Th
      cells, albeit at low levels, and are differentially induced by Ag and Th
      polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2,
      SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of
      SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1,
      SOCS2, and cytokine-induced Src homology 2 protein expression. We further show
      that STAT1 signals play major roles in inducing SOCS expression in Th cells and
      that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in
      STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1
      activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is
      dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first
      report of IL-4-induced STAT1 activation in Th cells, and suggests that its
      induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact,
      overexpression of SOCS1 in Th2 cells represses STAT6 activation and profoundly
      inhibits IL-4-induced proliferation, while depletion of SOCS1 by an anti-sense
      SOCS1 cDNA construct enhances cell proliferation and induces constitutive
      activation of STAT6 in Th2 cells. These results are consistent with a model where
      IL-4 has dual effects on differentiating T cells: it simulates
      proliferation/differentiation through STAT6 and autoregulates its effects on Th2
      growth and effector functions via STAT1-dependent up-regulation of SOCS proteins.

PMID- 15240660
TI  - C3a and C3b activation products of the third component of complement (C3) are
      critical for normal liver recovery after toxic injury.
AB  - Although the complement system has been implicated in liver regeneration after
      toxic injury and partial hepatectomy, the mechanism or mechanisms through which
      it participates in these processes remains ill-defined. In this study, we
      demonstrate that complement activation products (C3a, C3b/iC3b) are generated in
      the serum of experimental mice after CCl(4) injection and that complement
      activation is required for normal liver regeneration. Decomplementation by cobra
      venom factor resulted in impaired entry of hepatocytes into S phase of the cell
      cycle. In addition, livers from C3-deficient (C3(-/-)) mice showed similarly
      impaired proliferation of hepatocytes, along with delayed kinetics of both
      hepatocyte hyperplasia and removal of injured liver parenchyma. Restoration of
      hepatocyte proliferative capabilities of C3(-/-) mice through C3a reconstitution,
      as well as the impaired regeneration of C3a receptor-deficient mice, demonstrated
      that C3a promotes liver cell proliferation via the C3a receptor. These findings,
      together with data showing two waves of complement activation, indicate that C3
      activation is a pivotal mechanism for liver regeneration after CCl(4) injury,
      which fulfills multiple roles; C3a generated early after toxin injection is
      relevant during the priming of hepatocytes, whereas C3 activation at later times
      after CCl(4) treatment contributes to the clearance of injured tissue.

PMID- 15240661
TI  - Cholera toxin prevents Th1-mediated autoimmune disease by inducing immune
      deviation.
AB  - Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, is known for
      its properties as a mucosal adjuvant that promotes Th2 or mixed Th1 + Th2
      responses. In this study, we explore the ability of CT to act as a systemic
      adjuvant to counteract the Th1 response leading to experimental autoimmune
      uveitis. We report that susceptible B10.RIII mice immunized with a uveitogenic
      regimen of the retinal Ag interphotoreceptor retinoid-binding protein could be
      protected from disease by a single systemic injection of as little as 2 micro g
      of CT at the time of immunization. The protected mice were not immunosuppressed,
      but rather displayed evidence of immune deviation. Subsequent adaptive responses
      to interphotoreceptor retinoid-binding protein showed evidence of Th2
      enhancement, as indicated by reduced delayed-type hypersensitivity in the context
      of enhanced Ag-specific lymphocyte proliferation and IL-4 production. Ag-specific
      production of several other cytokines, including IFN-gamma, was not appreciably
      altered. The inhibitory effect of CT was dependent on the enzymatic A subunit of
      CT, because the cell-binding B subunit alone could not block disease development.
      Mice given CT displayed detectable IL-4 levels in their serum within hours of CT
      administration. This innate IL-4 production was critical for protection, as
      infusion of neutralizing Ab against IL-4 to mice, given a uveitogenic
      immunization and treated with CT, counteracted immune deviation and abrogated
      protection. Our data indicate that systemic administration of CT inhibits
      experimental autoimmune uveitis by skewing the response to the uveitogenic
      autoantigen to a nonpathogenic phenotype.

PMID- 15240662
TI  - Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA
      immunity.
AB  - This study assessed the roles of the postnatal lymphotoxin-beta receptor
      (LTbetaR)-mediated signals in the gut-associated lymphoreticular tissues of mice
      for subsequent regulation of Ag-specific intestinal IgA responses. Blockade of
      LTbetaR-dependent events by postnatal administration of the fusion protein of
      LTbetaR and IgG Fc (LTbetaR-Ig) reduced both the size and numbers of Peyer's
      patches (PP) without influencing the PP microarchitecture. Interestingly,
      inhibition of LTbetaR-dependent signaling revealed significant reductions in the
      formation of follicular dendritic cell clusters in mesenteric lymph nodes (MLN).
      Furthermore, these postnatal signaling events controlled the development of
      isolated lymphoid follicles (ILF) because treatment with LTbetaR-Ig eliminated
      the formation of ILF. LTbetaR-Ig-treated mice with altered microarchitecture of
      MLN and lacking ILF were still able to produce significant Ag-specific mucosal
      IgA responses after oral immunization; however, the levels were significantly
      lower than those seen in control mice. These results imply the importance of ILF
      for Ag-specific intestinal immunity. However, mice treated with both TNFR55-Ig
      and LTbetaR-Ig in utero, which lack PP and MLN, but retain intact ILF, failed to
      induce Ag-specific IgA responses after oral immunization. These findings
      demonstrate that ILF are not essential for induction of intestinal IgA Ab
      responses to orally administered Ag. Furthermore, the induction of intestinal IgA
      Ab responses requires the proper maintenance of the MLN microarchitecture,
      including a follicular dendritic cell network.

PMID- 15240663
TI  - Tec kinase migrates to the T cell-APC interface independently of its pleckstrin
      homology domain.
AB  - Tec is the prototypical member of the Tec tyrosine kinases family, which plays an
      important role in T cell signaling. We show in this study that Tec translocates
      to the immunological synapse when a T cell contacts a dendritic cell.
      Surprisingly, the presence of the pleckstrin homology (PH) domain of Tec is not
      required for this accumulation, and despite a strong activation of 3'
      phosphorylated phosphoinositide lipids synthesis during the synapse formation,
      the Tec PH domain is not redistributed to the T cell plasma membrane. In
      contrast, we demonstrate that an active Src homology 3 domain is absolutely
      required, underlining the essential role played by this part of the molecule in
      the recruitment and/or stabilization of Tec at the immunological synapse. Our
      results nevertheless suggest that the PH domain controls the kinase activity of
      the molecule in vivo. We finally demonstrate that the two domains are necessary
      to trigger transcriptional events following Ag presentation. These data support a
      model in which the plasma membrane recruitment of the PH-containing protein Tec
      is not dependent on the production of 3'-phosphorylated phosphoinositide lipids
      by the PI3K, but rather on an intact Src homology 3 domain.

PMID- 15240664
TI  - K+ channel expression during B cell differentiation: implications for
      immunomodulation and autoimmunity.
AB  - Using whole-cell patch-clamp, fluorescence microscopy and flow cytometry, we
      demonstrate a switch in potassium channel expression during differentiation of
      human B cells from naive to memory cells. Naive and IgD(+)CD27(+) memory B cells
      express small numbers of the voltage-gated Kv1.3 and the Ca(2+)-activated
      intermediate-conductance IKCa1 channel when quiescent, and increase IKCa1
      expression 45-fold upon activation with no change in Kv1.3 levels. In contrast,
      quiescent class-switched memory B cells express high levels of Kv1.3 (
      approximately 2000 channels/cell) and maintain their Kv1.3(high) expression after
      activation. Consistent with their channel phenotypes, proliferation of naive and
      IgD(+)CD27(+) memory B cells is suppressed by the specific IKCa1 inhibitor TRAM
      34 but not by the potent Kv1.3 blocker Stichodactyla helianthus toxin, whereas
      the proliferation of class-switched memory B cells is suppressed by Stichodactyla
      helianthus toxin but not TRAM-34. These changes parallel those reported for T
      cells. Therefore, specific Kv1.3 and IKCa1 inhibitors may have use in therapeutic
      manipulation of selective lymphocyte subsets in immunological disorders.

PMID- 15240665
TI  - Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates
      the requirement for CD4 T cells in the development of type 1 diabetes.
AB  - Although HLA-DQ8 has been implicated as a key determinant of genetic
      susceptibility to human type 1 diabetes, spontaneous diabetes has been observed
      in HLA-DQ8 transgenic mice that lack expression of murine MHC class II molecules
      (mII(-/-)) only when the potent costimulatory molecule, B7.1, is transgenically
      expressed on pancreatic beta cells. To study the contribution of HLA-DQ8 to the
      development of diabetes in this model, we crossed RIP-B7.1mII(-/-) mice with a
      set of transgenic mouse lines that differed in their HLA-DQ8 expression patterns
      on APC subpopulations, in particular dendritic cells and cortical thymic
      epithelial cells. Surprisingly, we found that even in the absence of HLA-DQ8 and
      CD4 T cells, a substantial fraction of the RIP-B7.1mII(-/-) mice developed
      diabetes. This disease process was remarkable for not only showing insulitis, but
      also inflammatory destruction of the exocrine pancreas with diffusely up
      regulated expression of MHC class I and ICAM-1 molecules. Expression of HLA-DQ8
      markedly increased the kinetics and frequency of diabetes, with the most severe
      disease in the lines with the highest levels of HLA-DQ8 on cortical thymic
      epithelial cells and the largest numbers of CD4 T cells. However, the adoptive
      transfer of diabetes was not HLA-DQ8-dependent and disease could be rapidly
      induced with purified CD8 T cells alone. Expression of B7.1 in the target tissue
      can thus dramatically alter the cellular and molecular requirements for the
      development of autoimmunity.

PMID- 15240666
TI  - Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal
      activity of antitumor monoclonal antibodies in murine tumor models.
AB  - Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b.
      Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for
      antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18)
      of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated
      tumors. Recent data indicated that barley beta-1,3;1,4-glucan given orally
      similarly potentiated the activity of antitumor mAb, leading to enhanced tumor
      regression and survival. This investigation showed that orally administered yeast
      beta-1,3;1,6-glucan functioned similarly to barley beta-1,3;1,4-glucan with
      antitumor mAb. With both oral beta-1,3-glucans, a requirement for iC3b on tumors
      and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in
      mice deficient in C3 or CR3. Barley and yeast beta-1,3-glucan were labeled with
      fluorescein to track their oral uptake and processing in vivo. Orally
      administered beta-1,3-glucans were taken up by macrophages that transported them
      to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages
      degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan
      fragments that were taken up by the CR3 of marginated granulocytes. These
      granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b
      opsonized tumor cells following their recruitment to a site of complement
      activation resembling a tumor coated with mAb.

PMID- 15240667
TI  - B cell-activating factor belonging to the TNF family (BAFF)-R is the principal
      BAFF receptor facilitating BAFF costimulation of circulating T and B cells.
AB  - BAFF (B cell-activating factor belonging to the TNF family) is a cell survival
      and maturation factor for B cells, and overproduction of BAFF is associated with
      systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane
      activator and calcium modulator and cyclophilin ligand interactor (TACI), and B
      cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the
      predominant BAFF receptor expressed on peripheral B cells, in both humans and
      mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti-
      micro responses. The other BAFF receptors showed a much more restricted
      expression pattern, suggestive of specialized roles. BCMA was expressed by
      germinal center B cells, while TACI was expressed predominantly by splenic
      transitional type 2 and marginal zone B cells, as well as activated B cells, but
      was notably absent from germinal center B cells. BAFF was also an effective
      costimulator for T cells, and this costimulation occurs entirely through BAFF-R.
      BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T
      cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF
      costimulation. Thus, BAFF-R is important not only for splenic B cell maturation,
      but is the major mediator of BAFF-dependent costimulatory responses in peripheral
      B and T cells.

PMID- 15240669
TI  - IL-10 plays an important role in the homeostatic regulation of the autoreactive
      repertoire in naive mice.
AB  - We have previously shown that naive SJL (H-2(s)) mice, which are highly
      susceptible to myelin proteolipid protein (PLP)-induced experimental autoimmune
      encephalomyelitis (EAE), have a very high frequency (1/20,000 CD4 T cells) of
      PLP(139-151)-reactive T cells in the naive repertoire. In this study, we examine
      the function of this endogenous PLP(139-151)-reactive repertoire in vivo and find
      that this repertoire encompasses the precursors of pathogenic T cells. Because
      SJL mice do not develop spontaneous EAE, we have explored the mechanisms that
      keep this autopathogenic repertoire in check and prevent the development of
      spontaneous autoimmunity. We crossed IL-4 and IL-10 deficiency onto the SJL
      background and analyzed the roles of these two immunoregulatory cytokines in
      regulating the size and effector function of the endogenous PLP(139-151)-reactive
      repertoire and development of autoimmune disease. We find that IL-10 is important
      in the homeostatic regulation of the endogenous PLP(139-151)-reactive repertoire
      in that it both limits the size of the repertoire and prevents development of
      effector autoaggressive T cells. SJL IL-10(-/-) mice with high numbers of PLP(139
      151)-specific precursors in the repertoire did not develop spontaneous EAE, but
      when they were injected with pertussis toxin, they showed atypical clinical signs
      of EAE with small numbers of typical mononuclear cell infiltrates predominantly
      in the meninges. EAE could be inhibited by prior tolerization of the mice with
      soluble PLP(139-151) peptide. These findings indicate that IL-10 may contribute
      to the regulation of the endogenous autoimmune repertoire.

PMID- 15240668
TI  - Decreased E47 in senescent B cell precursors is stage specific and regulated
      posttranslationally by protein turnover.
AB  - The E2A-encoded transcription factor E47 is crucial to B lymphopoiesis. Senescent
      BALB/c mice ( approximately 2 years old) had reduced pre-B cells ex vivo. Pro
      B/early pre-B cells from these aged mice, both ex vivo and in vitro, were
      deficient in E47 protein. In vitro, IL-7 expanded pro-B/early pre-B cells from
      young BALB/c mice expressed E47 protein that was relatively stable over a 5-h
      period. Cultured senescent pro-B/early pre-B cells exhibited reduced E47 protein
      stability with approximately 50-90% loss of E47 over the same time period.
      Degradation of E47 was effectively blocked by the proteasome inhibitor
      lactacystin as well as calpain I and II inhibitors; E2A proteins were also shown
      to undergo ubiquitination. Although senescent B cell precursors expressed less
      E47 protein, E47 mRNA levels and turnover were normal. Therefore, E47 protein
      levels are reduced relatively early in B lineage differentiation in senescence
      and the decline in E47 protein occurs via increased protein degradation by
      proteasome and, possibly, calpain pathways. In contrast, normal E47 protein
      levels were observed within the highly reduced pre-B cell pool in aged mice. This
      suggests that pre-B cells in senescence undergo selection based on E47
      expression. Increased degradation rates and lower steady-state levels were also
      observed for the transcription factors Pax-5/BSAP, Bob-1, and Ikaros, but this
      was not a general property of all proteins in aged B cell precursors. Therefore,
      altered turnover of multiple, select proteins crucial to B cell development may
      contribute to diminished B lymphopoiesis in old age.

PMID- 15240670
TI  - No intrinsic deficiencies in CD8+ T cell-mediated antitumor immunity with aging.
AB  - Aging is associated with a decline in immune function, particularly within the T
      cell compartment. Because CD8(+) T cells are critical mediators of protective
      immunity against cancer, which arises more frequently with advancing age, it is
      important to understand how aging affects T cell-based antitumor responses. We
      used our DUC18 T cell/CMS5 tumor model system to examine the ability of both aged
      APCs and aged, tumor-specific CD8(+) T cells to mount protective responses to
      tumors in vivo. An assessment of aged DUC18 T cells in vitro showed a naive
      phenotype, but impaired proliferation in response to anti-CD3 and anti-CD28
      stimulation. We found that DCs from young and old recipient mice are comparable
      phenotypically, and endogenous APCs in these mice are equally able to prime
      adoptively transferred young DUC18 T cells. Even when aged DUC18 T cells are
      transferred into aged CMS5-challenged mice, Ag-specific proliferation and CD25
      expression are similar to those found when young DUC18 T cells are transferred
      into young mice. Although trafficking to tumor sites appears unequal, old and
      young DUC18 T cells reject primary CMS5 challenges to the same degree and with
      similar kinetics. Overall, we found no loss of endogenous APC function or
      intrinsic defects in CD8(+) DUC18 T cells with advanced age. Therefore, when
      young and old tumor-specific T cell populations are equivalently sized, CD8(+) T
      cell-mediated antitumor immunity in our system is not impaired by age, a finding
      that has positive implications for T cell-based immunotherapies.

PMID- 15240671
TI  - Differential roles for CCR5 expression on donor T cells during graft-versus-host
      disease based on pretransplant conditioning.
AB  - The coordinated expression of chemokines and receptors may be important in the
      directed migration of alloreactive T cells during graft-vs-host disease (GVHD).
      Recent work demonstrated in a murine model that transfer of CCR5-deficient (CCR5(
      /-)) donor cells to nonconditioned haploidentical recipients resulted in reduced
      donor cell infiltration in liver and lymphoid tissues compared with transfer of
      CCR5(+/+) cells. To investigate the function of CCR5 during GVHD in conditioned
      transplant recipients, we transferred CCR5(-/-) or wild-type C57BL/6 (B6) T cells
      to lethally irradiated B6D2 recipients. Unexpectedly, we found an earlier time to
      onset and a worsening of GVHD using CCR5(-/-) T cells, which was associated with
      significant increases in the accumulation of alloreactive CD4(+) and CD8(+) T
      cells in liver and lung. Conversely, the transfer of CCR5(-/-) donor cells to
      nonirradiated recipients led to reduced infiltration of target organs, confirming
      previous studies and demonstrating that the role of CCR5 on donor T cells is
      dependent on conditioning of recipients. Expression of proinflammatory chemokines
      in target tissues was dependent on conditioning of recipients, such that CXCL10
      and CXCL11 were most highly expressed in tissues of irradiated recipients during
      the first week post-transplant. CCR5(-/-) T cells were shown to have enhanced
      migration to CXCL10, and blocking this ligand in vivo improved survival in
      irradiated recipients receiving CCR5(-/-) T cells. Our data indicate that the
      effects of inhibiting CCR5/ligand interaction on donor T cells during GVHD differ
      depending on conditioning of recipients, a finding with potentially important
      clinical significance.

PMID- 15240672
TI  - FTY720-enhanced T cell homing is dependent on CCR2, CCR5, CCR7, and CXCR4:
      evidence for distinct chemokine compartments.
AB  - FTY720 stimulates CCR7-driven T cell homing to peripheral lymph nodes (LN) by
      direct activation of sphingosine 1-phosphate receptors, along with the
      participation of multidrug transporters, 5-lipoxygenase, and G protein-coupled
      receptors for chemokines. In this study, we demonstrate that FTY720 also directly
      stimulates in vitro T cell chemotaxis to CCR2-CCL2, but not to a variety of other
      chemokines, including CCR5-CCL3/4/5 and CXCR4-CXCL12. FTY720 influences CCR2-CCL2
      driven migration through activation of the multidrug transporters, Abcb1 and
      Abcc1, and through 5-lipoxygenase activity. In vivo administration of FTY720
      induces chemokine-dependent migration of T cells in the thymus, peripheral blood,
      LN, and spleen. The CCR7 and CCR2 chemokine ligands are required for both T cell
      sequestration in LN and thymic T cell egress following FTY720 administration.
      Furthermore, FTY720 administration uncovers a requirement for CXCR4 ligands for
      LN homing, but not for thymic egress, and CCR5 for thymic egress, but not LN
      homing. FTY720-driven splenic and peripheral blood T cell egress are both
      independent of CCR2, CCR5, CCR7, or CXCR4. These results indicate that FTY720-
      and sphingosine 1-phosphate receptor-stimulated T cell migration are dependent on
      the restricted usage of chemokine receptor-ligand pairs within discrete anatomic
      compartments.

PMID- 15240673
TI  - Antigen-specific lymphocyte sequestration in lymphoid organs: lack of essential
      roles for alphaL and alpha4 integrin-dependent adhesion or Galphai protein
      coupled receptor signaling.
AB  - Selective lymphocyte sequestration was described over 30 years ago as the
      transient withdrawal of Ag-specific lymphocytes from the circulation as a result
      of their activation in secondary lymphoid organs. We used a TCR-transgenic
      adoptive transfer system to further characterize the Ag and adjuvant dependence
      of this process in mice. In addition, we examined the contribution of the
      alpha(L) and alpha(4) integrin chains as well as Galpha(i) protein-coupled
      receptor signaling to the retention of Ag-specific T cells in peripheral lymph
      nodes. Our results demonstrate that selective lymphocyte sequestration is T cell
      autonomous and adjuvant independent, and that the duration of sequestration is
      not controlled by the continued presence of Ag in secondary lymphoid organs. This
      process is not critically dependent on the alpha(L) and alpha(4) integrin chains
      or Galpha(i) protein-coupled receptor signaling. Selective lymphocyte
      sequestration may be mediated by redundant mechanisms and/or controlled by novel
      or nonclassical adhesion or trafficking molecules.

PMID- 15240674
TI  - Nitric oxide regulates immune cell bioenergetic: a mechanism to understand
      immunomodulatory functions of nitric oxide-releasing anti-inflammatory drugs.
AB  - The 2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester (NCX-4016) is a NO
      releasing derivative of aspirin. In this study, we provide evidence that NCX-4016
      delivered to PMBC-derived T lymphocytes and monocytes causes a transitory
      inhibition of cell respiration and approximately 50% reduction of cellular ATP,
      which translates in a time-reversible inhibition of cell proliferation and IL-2,
      IL-4, IL-5, and IFN-gamma secretion. Exposure of lymphocytes and monocytes to
      aspirin, 2-(acetyloxy)benzoic acid 3-(hydroxymethyl)phenyl ester (NCX-4017), a
      non-NO-releasing analog of NCX-4016, and cyclooxygenase inhibitors, reduced PG
      formation, but has no effect on cytokine/chemokine release. In contrast,
      delivering NO with (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium
      1,2 diolate (DETA-NO) reproduced most of the metabolic and anti-cytokine
      activities of NCX-4016. Scavenging NO with hemoglobin or adding selective
      substrates of complex II, III, and IV of the mitochondrial respiratory chain
      reverses NCX-4016' inhibitory activities. Exposure to DETA-NO and NCX-4016
      enhances glucose uptake, glycolytic rate, and lactate generation in CD3/CD28
      costimulated lymphocytes, while reduced citric acid cycle intermediates. These
      effects were not reproduced by selective and nonselective cyclooxygenase 2
      inhibitors. In summary, we demonstrated that exposure of lymphocytes to NCX-4016
      causes a metabolic hypoxia that inhibits lymphocyte reactivity to costimulatory
      molecules, providing a potential counteregulatory mechanism to control activated
      immune system.

PMID- 15240675
TI  - Bcl6 acts as an amplifier for the generation and proliferative capacity of
      central memory CD8+ T cells.
AB  - Central memory CD8(+) T cells (T(CM)) are considered to be more efficient than
      effector ones (T(EM)) for mediating protective immunity. The molecular mechanism
      involved in the generation of these cells remains elusive. Because Bcl6 plays a
      role in the generation and maintenance of memory CD8(+) T cells, we further
      examined this role in the process in relation to T(CM) and T(EM) subsets. In this
      study, we show that T(CM) and T(EM) were functionally identified in CD62L(+) and
      CD62L(-) memory (CD44(+)Ly6C(+)) CD8(+) T cell subsets, respectively. Although
      T(CM) produced similar amounts of IFN-gamma and IL-2 to T(EM) after anti-CD3
      stimulation, the cell proliferation capacity after stimulation and tissue
      distribution profiles of T(CM) differed from those of T(EM). Numbers of T(CM)
      were greatly reduced and elevated in spleens of Bcl6-deficient and lck-Bcl6
      transgenic mice, respectively, and those of T(EM) were constant in nonlymphoid
      organs of these same mice. The majority of Ag-specific memory CD8(+) T cells in
      spleens of these mice 10 wk after immunization were T(CM), and the number
      correlated with Bcl6 expression in T cells. The proliferation of Ag-specific
      memory CD8(+) T cells upon secondary stimulation was dramatically up-regulated in
      lck-Bcl6 transgenic mice, and the adoptive transfer experiments with Ag-specific
      naive CD8(+) T cells demonstrated that some of the up-regulation was due to the
      intrinsic effect of Bcl6 in the T cells. Thus, Bcl6 is apparently a crucial
      factor for the generation and secondary expansion of T(CM).

PMID- 15240676
TI  - Human B cells express functional TRAIL/Apo-2 ligand after CpG-containing
      oligodeoxynucleotide stimulation.
AB  - CpG-containing oligodeoxynucleotides (CpG ODN) have broad-ranging
      immunostimulatory effects, including the generation of antitumor immune
      responses. Analysis of different CpG ODN have identified two classes: CpG-A ODN,
      which stimulate high levels of IFN-alpha production from plasmacytoid dendritic
      cells and weakly activate B cells, and CpG-B ODN, which strongly activate B cells
      but stimulate low production of IFN-alpha from plasmacytoid dendritic cells.
      Previously, we observed that CpG-B ODN (2006) induces TRAIL/Apo-2 ligand (Apo-2L)
      mediated killing of tumor cells by CD14(+) PBMC. In this study, we extend our
      investigation of CpG ODN-induced TRAIL/Apo-2L expression and activity in PBMC to
      include CpG-A ODN. Of the two classes, IFN-alpha production and TRAIL/Apo-2L
      mediated killing of tumor cells was greatest with CpG-A ODN. Surprisingly,
      CD3(+), CD14(+), CD19(+), and CD56(+) PBMC expressed high levels of TRAIL/Apo-2L
      following CpG-A ODN stimulation. When isolated, the CD19(+) PBMC (B cells) were
      able to kill tumor cells in a TRAIL/Apo-2L-dependent manner. As with CD14(+)
      PBMC, CD19(+) sorted B cells were capable of up-regulating TRAIL/Apo-2L
      expression when stimulated with IFN-alpha alone. Interestingly, agonist anti-CD40
      mAb further enhanced the IFN-alpha-induced TRAIL/Apo-2L expression on CD19(+) B
      cells. These results are the first to demonstrate human B cell-mediated killing
      of tumor cells in a TRAIL/Apo-2L-dependent fashion.

PMID- 15240677
TI  - IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor
      immunity: comparative evaluation of IL-2, IL-15, and IL-21.
AB  - Cytokines that use the common receptor gamma-chain for regulating CD8(+) T cell
      responses to Ag include IL-2, IL-15, and the recently identified IL-21. The
      ability of these cytokines to regulate antitumor activity in mice has generated
      considerable interest in understanding their mode of action. In this study we
      compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against
      tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21
      treated mice. By monitoring both endogenous and adoptively transferred tumor Ag
      specific CD8(+) T cells, it was determined that IL-21 activities overlap with
      those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal
      expansion. However, unlike IL-2 treatment, which induces activation-induced cell
      death, IL-21 sustained CD8(+) T cell numbers long term as a result of increased
      survival, an effect often attributed to IL-15. These findings indicate that the
      mechanisms used by IL-21 to promote CD8(+) T cell responses offer unique
      opportunities for its use in malignant diseases and infections.

PMID- 15240678
TI  - Differential requirement for IFN-gamma in CTL maturation in acute murine graft
      versus-host disease.
AB  - Although IFN-gamma is the archetypal Th1 cytokine, its role in CTL maturation is
      uncertain. We used an in vivo mouse model of CTL development, parent-into-F(1)
      acute graft-vs-host disease (AGVHD), to evaluate this issue. In AGVHD, transfer
      of naive parental T cells into F(1) hosts stimulates the development of
      allospecific CTL effectors that eliminate host lymphocytes, particularly B cells.
      Complete elimination of IFN-gamma, using IFN-gamma-deficient donors and
      administering anti-IFN-gamma mAb, suppressed B cell elimination, down-regulated
      TNF-alpha production, and enhanced Th2 cytokine production, but did not allow the
      B cell expansion characteristic of chronic GVHD (CGVHD). Because complete CTL
      inhibition results in full-blown CGVHD that is IFN-gamma independent, these
      observations indicate that IFN-gamma elimination only partially blocks CTL
      development. IFN-gamma elimination did not inhibit donor T cell engraftment or
      activation in the AGVHD model, but almost completely blocked Fas/Fas ligand
      (FasL) gene expression, protein up-regulation, and Fas/FasL-mediated CTL killing.
      In contrast, IFN-gamma elimination only partially inhibited perforin gene
      expression and perforin-mediated CTL activity. The contributions of IFN-gamma to
      CTL development were indirect, because IFN-gamma receptor-deficient donor cells
      differentiated normally into allospecific CTLs. Consistent with the view that the
      Fas/FasL and perforin pathways each mediate CTL killing in AGVHD, the absence of
      both perforin and IFN-gamma (perforin knockout donor cells and anti-IFN-gamma
      mAb) converted AGVHD to CGVHD. Thus, both IFN-gamma-dependent induction of
      Fas/FasL and IFN-gamma-independent induction of perforin contribute to CTL
      mediated elimination of host B cells in AGVHD. Suppression of both pathways is
      required for typical CGVHD development.

PMID- 15240679
TI  - Rap1 signaling is required for suppression of Ras-generated reactive oxygen
      species and protection against oxidative stress in T lymphocytes.
AB  - Transient production of reactive oxygen species (ROS) plays an important role in
      optimizing transcriptional and proliferative responses to TCR signaling in T
      lymphocytes. Conversely, chronic oxidative stress leads to decreased
      proliferative responses and enhanced transcription of inflammatory gene products,
      and is thought to underlie the altered pathogenic behavior of T lymphocytes in
      some human diseases, such as rheumatoid arthritis (RA). Although the signaling
      mechanisms regulating ROS production in T lymphocytes has not been identified,
      activation of the small GTPase Ras has been shown to couple agonist stimulation
      to ROS production in other cell types. We find that Ras signaling via Ral
      stimulates ROS production in human T lymphocytes, and is required for TCR and
      phorbol ester-induced ROS production. The related small GTPase Rap1 suppresses
      agonist, Ras and Ral-dependent ROS production through a PI3K-dependent pathway,
      identifying a novel mechanism by which Rap1 can distally antagonize Ras signaling
      pathways. In synovial fluid T lymphocytes from RA patients we observed a high
      rate of endogenous ROS production, correlating with constitutive Ras activation
      and inhibition of Rap1 activation. Introduction of dominant-negative Ras into
      synovial fluid T cells restored redox balance, providing evidence that
      deregulated Ras and Rap1 signaling underlies oxidative stress and consequent
      altered T cell function observed in RA.

PMID- 15240680
TI  - Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine
      phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3',5'
      monophosphate and phosphatases.
AB  - Adenosine is a purine nucleoside with immunosuppressive activity that acts
      through cell surface receptors (A(1), A(2a), A(2b), A(3)) on responsive cells
      such as T lymphocytes. IL-2 is a major T cell growth and survival factor that is
      responsible for inducing Jak1, Jak3, and STAT5 phosphorylation, as well as
      causing STAT5 to translocate to the nucleus and bind regulatory elements in the
      genome. In this study, we show that adenosine suppressed IL-2-dependent
      proliferation of CTLL-2 T cells by inhibiting STAT5a/b tyrosine phosphorylation
      that is associated with IL-2R signaling without affecting IL-2-induced
      phosphorylation of Jak1 or Jak3. The inhibitory effect of adenosine on IL-2
      induced STAT5a/b tyrosine phosphorylation was reversed by the protein tyrosine
      phosphatase inhibitors sodium orthovanadate and bpV(phen). Adenosine dramatically
      increased Src homology region 2 domain-containing phosphatase-2 (SHP-2) tyrosine
      phosphorylation and its association with STAT5 in IL-2-stimulated CTLL-2 T cells,
      implicating SHP-2 in adenosine-induced STAT5a/b dephosphorylation. The inhibitory
      effect of adenosine on IL-2-induced STAT5a/b tyrosine phosphorylation was
      reproduced by A(2) receptor agonists and was blocked by selective A(2a) and A(2b)
      receptor antagonists, indicating that adenosine was mediating its effect through
      A(2) receptors. Inhibition of STAT5a/b phosphorylation was reproduced with cell
      permeable 8-bromo-cAMP or forskolin-induced activation of adenylyl cyclase, and
      blocked by the cAMP/protein kinase A inhibitor Rp-cAMP. Forskolin and 8-bromo
      cAMP also induced SHP-2 tyrosine phosphorylation. Collectively, these findings
      suggest that adenosine acts through A(2) receptors and associated cAMP/protein
      kinase A-dependent signaling pathways to activate SHP-2 and cause STAT5
      dephosphorylation that results in reduced IL-2R signaling in T cells.

PMID- 15240681
TI  - SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of
      programmed death 1 upon primary human T cell stimulation, but only receptor
      ligation prevents T cell activation.
AB  - To study the cis- and trans-acting factors that mediate programmed death 1 (PD-1)
      signaling in primary human CD4 T cells, we constructed a chimeric molecule
      consisting of the murine CD28 extracellular domain and human PD-1 cytoplasmic
      tail. When introduced into CD4 T cells, this construct mimics the activity of
      endogenous PD-1 in terms of its ability to suppress T cell expansion and cytokine
      production. The cytoplasmic tail of PD-1 contains two structural motifs, an ITIM
      and an immunoreceptor tyrosine-based switch motif (ITSM). Mutation of the ITIM
      had little effect on PD-1 signaling or functional activity. In contrast, mutation
      of the ITSM abrogated the ability of PD-1 to block cytokine synthesis and to
      limit T cell expansion. Further biochemical analyses revealed that the ability of
      PD-1 to block T cell activation correlated with recruitment of Src homology
      region 2 domain-containing phosphatase-1 (SHP-1) and SHP-2, and not the adaptor
      Src homology 2 domain-containing molecule 1A, to the ITSM domain. In TCR
      stimulated T cells, SHP-2 associated with PD-1, even in the absence of PD-1
      engagement. Despite this interaction, the ability of PD-1 to block T cell
      activation required receptor ligation, suggesting that colocalization of PD-1
      with CD3 and/or CD28 may be necessary for inhibition of T cell activation.

PMID- 15240682
TI  - T cell biasing by activated dendritic cells.
AB  - We have previously reported that the ligation of FcgammaRs on activated
      macrophages affected their production of cytokines and their ability to influence
      T cell activation. Dendritic cells (DC) are important APCs that also express
      FcgammaR. In the present work, we sought to determine whether DC responded to
      immune complexes in a manner similar to macrophages. We confirmed that activated
      murine DC produced IL-12, and, as a result, induced naive T cells to produce
      primarily IFN-gamma upon stimulation. However, DC activated in the presence of
      immune complexes shut off their production of IL-12p70 and induced a Th2-like
      cytokine response. Thus, DC respond to immune complexes by altering their
      cytokine production, which, in turn, influences T cell responses. A DC transfer
      experiment was performed to determine the extent that APC exposure to immune
      complexes could influence adaptive immune responses. Vaccination of mice with Ag,
      along with DC that were activated in the presence of immune complexes, resulted
      in higher levels of Ag-specific IgG1 Ab, relative to mice that were vaccinated
      with activated DC and Ag alone. The mechanism by which DC altered their cytokine
      production in response to immune complexes was different from macrophages.
      Macrophages down-regulated the transcription of both the p40 and p35 subunits of
      IL-12, whereas DC decreased only p35 expression. We conclude that APCs expressing
      FcgammaR on their surface can respond to immune complexes by shutting off IL-12
      biosynthesis, to prevent the Th1-type T cell biasing that normally accompanies
      innate immune activation.

PMID- 15240683
TI  - TGF-beta1 disrupts endotoxin signaling in microglial cells through Smad3 and MAPK
      pathways.
AB  - Human formyl peptide receptor-like 1 and its mouse homologue formyl peptide
      receptor 2 (FPR2) are G protein-coupled receptors used by a number of exogenous
      and host-derived chemotactic peptides, including the 42 aa form of beta amyloid
      peptide, a causative factor of Alzheimer's disease. Functional FPR2 was induced
      by bacterial LPS in murine microglial cells, the resident phagocytic cells that
      play a pivotal role in inflammatory and immunological diseases in the CNS. To
      identify agents that may suppress microglial cell activation under
      proinflammatory conditions, we investigated the effect of TGF-beta1 on the
      expression of functional FPR2 by microglial cells activated by LPS. TGF-beta1
      dose-dependently inhibited the mRNA expression and function of FPR2 in LPS
      activated microglial cells. The inhibitory effect of TGF-beta1 was mediated by
      Smad3, a key signaling molecule coupled to the TGF-beta receptor, and the
      transcription coactivator, p300. Also, TGF-beta1 activates MAPKs in microglial
      cells that became refractory to further stimulation by LPS. These effects of TGF
      beta1 culminate in the inhibition of LPS-induced activation of NF-kappaB and the
      up-regulation of FPR2 in microglial cells. Thus, TGF-beta1 may exert a protective
      role in CNS diseases characterized by microglial cell activation by
      proinflammatory stimulants.

PMID- 15240684
TI  - Fully functional memory CD8 T cells in the absence of CD4 T cells.
AB  - The role of CD4 T cells in providing help to CD8 T cells in primary and secondary
      responses to infection remains controversial. Using recombinant strains of virus
      and bacteria expressing the same Ag, we determined the requirement for CD4 T
      cells in endogenous CD8 T cell responses to infection with vesicular stomatitis
      virus and Listeria monocytogenes (LM). Depletion of CD4 T cells had no effect on
      the frequency of primary or secondary vesicular stomatitis virus-specific CD8 T
      cells in either lymphoid or nonlymphoid tissues. In contrast, the primary LM
      specific CD8 T cell response was CD4 T cell dependent. Surprisingly, the LM
      specific CD8 T cell recall response was also CD4 T cell dependent, which
      correlated with a requirement for CD40/CD40L interactions. However, concomitant
      inhibition of CD40L and CD4 T cell removal revealed that these pathways may be
      operating independently. Importantly, despite the absence of CD4 T cells during
      the recall response or throughout the entire response, CD8 memory T cells were
      functional effectors and proliferated equivalently to their "helped"
      counterparts. These data call into question the contention that CD4 T cells
      condition memory CD8 T cells during the primary response and indicate that the
      principal role of CD4 T cells in generating CD8 memory cells after infection is
      augmentation of proliferation or survival through costimulatory signals.

PMID- 15240685
TI  - Nucleolin is a second component of the CD154 mRNA stability complex that
      regulates mRNA turnover in activated T cells.
AB  - CD154 (CD40L) mRNA turnover is regulated in part at the posttranscriptional level
      by a protein complex (termed Complex I) that binds to a highly CU-rich region of
      the 3'UTR. Polypyrimidine tract-binding protein (PTB) has previously been
      identified as a major RNA-binding protein in Complex I. Nondenaturing gel
      filtration of total extract from Jurkat T cells demonstrated that the CD154 mRNA
      binding activity migrates as a approximately 200-kDa complex, indicating the
      presence of multiple complex-associated proteins. We have currently undertaken a
      biochemical approach to further characterize Complex I and observed that it
      segregates over DEAE-Sepharose into two subcomplexes (termed I-L and I-U).
      Furthermore, nucleolin was identified as a component of both subcomplexes and was
      shown that it is the major RNA-binding protein in I-U. To directly demonstrate
      the biological significance of Complex I binding to the CD154 transcript,
      cytoplasm from human Jurkat cells was fractionated over a sucrose gradient and
      the different cellular fractions subjected to immunoprecipitation with anti-PTB
      and anti-nucleolin Abs. RT-PCR of the immunoprecipitated products using CD154
      specific primers clearly demonstrated that nucleolin and PTB are associated with
      CD154 mRNA in both the ribonucleoprotein and polysome fractions. These data
      strongly support a model whereby nucleolin and PTB are integral to the stability
      of CD154 mRNA and are components of the CD154 ribonucleoprotein particle
      associated with actively translating ribosomes.

PMID- 15240686
TI  - Kinase suppressor of Ras couples Ras to the ERK cascade during T cell
      development.
AB  - Ras signaling is critical for many developmental processes and requires the
      precise coordination of interactions among multiple downstream components. One
      mechanism by which this regulation is achieved is through the use of scaffolding
      molecules that coordinate the assembly of multimolecular complexes. Recently, the
      scaffolding molecule kinase suppressor of Ras (KSR) was isolated in genetic
      screens as a modifier of Ras signaling, although its contribution to regulating
      Ras-mediated activation of its different downstream effectors is not well
      understood. We have analyzed the role of KSR in linking Ras to the ERK cascade
      during positive selection. Our results demonstrate that KSR overexpression
      interferes with T cell development, an effect that requires the direct
      interaction between KSR and MEK. This functional effect correlates with the
      ability of KSR to uncouple Ras from the ERK cascade when overexpressed.

PMID- 15240687
TI  - FcR interactions do not play a major role in inhibition of experimental
      autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies.
AB  - It has been demonstrated that anti-CD154 mAb treatment effectively inhibits the
      development of experimental autoimmune encephalomyelitis (EAE). However, although
      it appears to prevent the induction of Th1 cells and reactivation of
      encephalitogenic T cells within the CNS, little information is available
      regarding the involvement of alternative mechanisms, nor has the contribution of
      Fc effector mechanisms in this context been addressed. By contrast, efficacy of
      anti-CD154 mAbs in models of allotransplantation has been reported to involve
      long-term unresponsiveness, potentially via activation of T regulatory cells, and
      recently was reported to depend on Fc-dependent functions, such as activated T
      cell depletion through FcgammaR or complement. In this study we demonstrate that
      anti-CD154 mAb treatment inhibits EAE development in SJL mice without apparent
      long-term unresponsiveness or active suppression of disease. To address whether
      the mechanism of inhibition of EAE by anti-CD154 mAb depends on its Fc effector
      interactions, we compared an anti-CD154 mAb with its aglycosyl counterpart with
      severely impaired FcgammaR binding and reduced complement binding activity with
      regard to their ability to inhibit clinical signs of EAE and report that both
      forms of the Ab are similarly protective. This observation was largely confirmed
      by the extent of leukocyte infiltration of the CNS; however, mice treated with
      the aglycosyl form may display slightly more proteolipid protein 139-151-specific
      immune reactivity. It is concluded that FcR interactions do not play a major role
      in the protective effect of anti-CD154 mAb in the context of EAE, though they may
      contribute to the full abrogation of peripheral peptide-specific lymphocyte
      responses.

PMID- 15240688
TI  - Basal Igalpha/Igbeta signals trigger the coordinated initiation of pre-B cell
      antigen receptor-dependent processes.
AB  - The pro-B to pre-B transition during B cell development is dependent upon surface
      expression of a signaling competent pre-B cell Ag receptor (pre-BCR). Although
      the mature form of the BCR requires ligand-induced aggregation to trigger
      responses, the requirement for ligand-induced pre-BCR aggregation in promoting B
      cell development remains a matter of significant debate. In this study, we used
      transmission electron microscopy on murine primary pro-B cells and pre-B cells to
      analyze the aggregation state of the pre-BCR. Although aggregation can be induced
      and visualized following cross-linking by Abs to the pre-BCR complex, our
      analyses indicate that the pre-BCR is expressed on the surface of resting cells
      primarily in a nonaggregated state. To evaluate the degree to which basal signals
      mediated through nonaggregated pre-BCR complexes can promote pre-BCR-dependent
      processes, we used a surrogate pre-BCR consisting of the cytoplasmic regions of
      Igalpha/Igbeta that is targeted to the inner leaflet of the plasma membrane of
      primary pro-B cells. We observed enhanced proliferation in the presence of low IL
      7, suppression of V(H)(D)J(H) recombination, and induced kappa light (L) chain
      recombination and cytoplasmic kappa L chain protein expression. Interestingly,
      Igalpha/Igbeta-mediated allelic exclusion was restricted to the B cell lineage as
      we observed normal TCRalphabeta expression on CD8-expressing splenocytes. This
      study directly demonstrates that basal signaling initiated through Igalpha/Igbeta
      containing complexes facilitates the coordinated control of differentiation
      events that are associated with the pre-BCR-dependent transition through the pro
      B to pre-B checkpoint. Furthermore, these results argue that pre-BCR aggregation
      is not a requirement for pre-BCR function.

PMID- 15240689
TI  - T cell immunity induced by live, necrotic, and apoptotic tumor cells.
AB  - The rules that govern the engagement of antitumor immunity are not yet fully
      understood. Ags expressed by tumor cells are prone to induce T cell tolerance
      unless the innate immune system is activated. It is unclear to what extent tumors
      engage this second signal link by the innate immune system. Apoptotic and
      necrotic (tumor) cells are readily recognized and phagocytosed by the cells of
      the innate immune system. It is unknown how this affects the tumor's
      immunogenicity. Using a murine melanoma (B16m) and lymphoma (L5178Y-R) model, we
      studied the clonal sizes and cytokine signatures of the T cells induced by these
      tumors in syngeneic mice when injected as live, apoptotic, and necrotic cells.
      Both live tumors induced a type 2 CD4 cell response characterized by the
      prevalent production of IL-2, IL-4, and IL-5 over IFN-gamma. Live, apoptotic, and
      necrotic cells induced CD4 (but no CD8) T cells of comparable frequencies and
      cytokine profiles. Therefore, live tumors engaged the second signal link, and
      apoptotic or necrotic tumor cell death did not change the magnitude or quality of
      the antitumor response. A subclone of L5178Y-R, L5178Y-S cells, were found to
      induce a high-frequency type 1 response by CD4 and CD8 cells that conveyed immune
      protection. The data suggest that the immunogenicity of tumors, and their
      characteristics to induce type 1 or type 2, CD4 or CD8 cell immunity is not
      primarily governed by signals associated with apoptotic or necrotic cell death,
      but is an intrinsic feature of the tumor itself.

PMID- 15240690
TI  - A tumor-associated glycoprotein that blocks MHC class II-dependent antigen
      presentation by dendritic cells.
AB  - Tumors evade immune surveillance despite the frequent expression of tumor
      associated Ags (TAA). Tumor cells escape recognition by CD8(+) T cells through
      several mechanisms, including down-regulation of MHC class I molecules and
      associated Ag-processing machinery. However, although it is well accepted that
      optimal anti-tumor immune responses require tumor-reactive CD4(+) T cells, few
      studies have addressed how tumor cells evade CD4(+) T cell recognition. In this
      study, we show that a common TAA, GA733-2, and its murine orthologue, mouse
      epithelial glycoprotein (mEGP), function in blocking MHC class II-restricted Ag
      presentation by dendritic cells. GA733-2 is a common TAA that is expressed
      normally at low levels by some epithelial tissues and a subset of dendritic
      cells, but at high levels on colon, breast, lung, and some nonepithelial tumors.
      We show that ectopic expression of mEGP or GA733-2, respectively, in dendritic
      cells derived from murine bone marrow or human monocytes results in a dose
      dependent inability to stimulate proliferation of Ag-specific or alloreactive
      CD4(+) T cells. Dendritic cells exposed to cell debris from tumors expressing
      mEGP are similarly compromised. Furthermore, mice immunized with dendritic cells
      expressing mEGP from a recombinant adenovirus vector exhibited a muted anti
      adenovirus immune response. The inhibitory effect of mEGP was not due to down
      regulation of functional MHC class II molecules or active suppression of T cells,
      and did not extend to T cell responses to superantigen. These results demonstrate
      a novel mechanism by which tumors may evade CD4(+) T cell-dependent immune
      responses through expression of a TAA.

PMID- 15240692
TI  - Oral tolerance to nickel requires CD4+ invariant NKT cells for the infectious
      spread of tolerance and the induction of specific regulatory T cells.
AB  - Previously, oral administration of nickel to C57BL/6 wild-type (WT) mice was
      shown to render both their splenic T cells and APCs (i.e., T cell-depleted spleen
      cells) capable of transferring nickel tolerance to naive syngeneic recipients.
      Moreover, sequential adoptive transfer experiments revealed that on transfer of
      tolerogenic APCs and immunization, the naive T cells of the recipients
      differentiated into regulatory T (Treg) cells. Here, we demonstrate that after
      oral nickel treatment Jalpha18(-/-) mice, which lack invariant NKT (iNKT) cells,
      were not tolerized and failed to generate Treg cells. However, transfer of APCs
      from those Jalpha18(-/-) mice did tolerize WT recipients. Hence, during oral
      nickel administration, tolerogenic APCs are generated that require iNKT cell help
      for the induction of Treg cells. To obtain this help, the tolerogenic APCs must
      address the iNKT cells in a CD1-restricted manner. When Jalpha18(-/-) mice were
      used as recipients of cells from orally tolerized WT donors, the WT Treg cells
      transferred the tolerance, whereas WT APCs failed to do so, although they proved
      tolerogenic on transfer to WT recipients. However, Jalpha18(-/-) recipients did
      become susceptible to the tolerogenicity of transferred WT APCs when they were
      reconstituted with IL-4- and IL-10-producing CD4(+) iNKT cells. We conclude that
      CD4(+) iNKT cells are required for the induction of oral nickel tolerance and, in
      particular, for the infectious spread of tolerance from APCs to T cells. Once
      induced, these Treg cells, however, can act independently of iNKT cells.

PMID- 15240691
TI  - Specific engagement of TLR4 or TLR3 does not lead to IFN-beta-mediated innate
      signal amplification and STAT1 phosphorylation in resident murine alveolar
      macrophages.
AB  - The innate immune response must be mobilized promptly yet judiciously via TLRs to
      protect the lungs against pathogens. Stimulation of murine peritoneal macrophage
      (PMphi) TLR4 or TLR3 by pathogen-associated molecular patterns (PAMPs) typically
      induces type I IFN-beta, leading to autocrine activation of the transcription
      factor STAT1. Because it is unknown whether STAT1 plays a similar role in the
      lungs, we studied the response of resident alveolar macrophages (AMphi) or
      control PMphi from normal C57BL/6 mice to stimulation by PAMPs derived from
      viruses (polyriboinosinic:polyribocytidylic acid, specific for TLR3) or bacteria
      (Pam(3)Cys, specific for TLR2, and repurified LPS, specific for TLR4). AMphi did
      not activate STAT1 by tyrosine phosphorylation on Y701 following stimulation of
      any of these three TLRs, but readily did so in response to exogenous IFN-beta.
      This unique AMphi response was not due to altered TLR expression, or defective
      immediate-early gene response, as measured by expression of TNF-alpha and three
      beta chemokines. Instead, AMphi differed from PMphi in not producing bioactive
      IFN-beta, as confirmed by ELISA and by the failure of supernatants from TLR
      stimulated AMphi to induce STAT1 phosphorylation in PMphi. Consequently, AMphi
      did not produce the microbicidal effector molecule NO following TLR4 or TLR3
      stimulation unless exogenous IFN-beta was also added. Thus, murine AMphi respond
      to bacterial or viral PAMPs by producing inflammatory cytokines and chemokines,
      but because they lack the feed-forward amplification typically mediated by
      autocrine IFN-beta secretion and STAT1 activation, require exogenous IFN to mount
      a second phase of host defense.

PMID- 15240693
TI  - Requirements of NK cells and proinflammatory cytokines in T cell-dependent
      neonatal autoimmune ovarian disease triggered by immune complex.
AB  - A model of neonatal autoimmune disease has been described recently in which an
      epitope-specific autoantibody to murine zona pellucida 3 induces severe ovarian
      disease in neonatal, but not adult, mice (neonatal AOD). The autoantibody forms
      immune complex with endogenous ovarian zona pellucida 3, and a pathogenic CD4(+)
      T cell response is triggered. The basis for the predominant neonatal
      susceptibility has not been clarified. In this study innate immunity, including
      neonatal NK cells, in neonatal AOD was investigated. Neonatal spleen contained
      readily detectable NK1.1(+)TCRVbeta(-), but not NK1.1(+)TCRVbeta(+), cells. Ab
      depletion of NK1.1(+)TCRVbeta(-) cells inhibited neonatal AOD development.
      Moreover, in adoptive transfer of neonatal AOD, recipient disease was ameliorated
      when either donor or recipient NK cells were depleted. Thus, NK cells operate in
      both induction and effector phases of the disease. IFN-gamma was produced by
      neonatal NK cells in vivo, and it may be important in neonatal AOD. Indeed,
      ovaries with neonatal AOD expressed high levels of IFN-gamma and TNF-alpha which
      correlated with disease severity, and the disease was inhibited by IFN-gamma or
      TNF-alpha Ab. Importantly, disease was enhanced by recombinant IFN-gamma, and
      treatment of T cell donors with IFN-gamma Ab also significantly reduced adoptive
      transfer of neonatal AOD. Finally, neonatal AOD was ameliorated in mice deficient
      in FcgammaRIII and was enhanced in FcgammaRIIB-deficient mice. We conclude that
      neonatal NK cells promote pathogenic T cell response at multiple stages during
      neonatal autoimmune disease pathogenesis. Also operative in neonatal AOD are
      other mediators of the innate system, including proinflammatory cytokines and
      FcgammaRIII signaling.

PMID- 15240694
TI  - Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice.
AB  - Cbl-b(-/-) mice have signaling defects that result in CD28-independent T cell
      activation, increased IL-2 production, hyper-reactive T cells, and increased
      autoimmunity. Although the increased autoimmunity in these mice is believed to
      result from the hyper-reactive T cells, the mechanisms leading from T cell hyper
      reactivity to autoimmunity remain unclear. Specifically, the function and
      interaction of CD4(+)CD25(+) regulatory T cells (T(reg)) and CD4(+)CD25(-)
      effector T cells (T(eff)) in Cbl-b(-/-) mice have not been examined. We now
      report that Cbl-b(-/-) CD4(+)CD25(+) T(reg) exhibit normal regulatory function in
      vitro. In contrast, the in vitro response of Cbl-b(-/-) CD4(+)CD25(-) T(eff) is
      abnormal, in that it is not inhibited by either Cbl-b(-/-) or wild-type T(reg).
      This resistance of Cbl-b(-/-) T(eff) to in vitro regulation is seen at the levels
      of both DNA synthesis and cell division. In addition to this resistance to
      CD4(+)CD25(+) T(reg), Cbl-b(-/-) T(eff) demonstrate in vitro resistance to
      inhibition by TGF-beta. This second form of resistance in Cbl-b(-/-) T(eff) is
      seen despite the expression of normal levels of type II TGF-beta receptors and
      normal levels of phosphorylated Smad3 after TGF-beta stimulation. Coupled with
      recent reports of resistance to T(reg) in T(eff) exposed to LPS-treated dendritic
      cells, our present findings suggest that resistance to regulation may be a
      relevant mechanism in both normal immune function and autoimmunity.

PMID- 15240695
TI  - TNF activates Syk protein tyrosine kinase leading to TNF-induced MAPK activation,
      NF-kappaB activation, and apoptosis.
AB  - Spleen tyrosine kinase (Syk), a nonreceptor protein kinase initially found to be
      expressed only in hemopoietic cells, has now been shown to be expressed in
      nonhemopoietic cells and to mediate signaling of various cytokines. Whether Syk
      plays any role in TNF signaling was investigated. Treatment of Jurkat T cells
      with TNF activated Syk kinase but not ZAP70, another member of Syk kinase family,
      and the optimum activation occurred at 10 s and with 1 nM TNF. TNF also activated
      Syk in myeloid and epithelial cells. TNF-induced Syk activation was abolished by
      piceatannol (Syk-selective inhibitor), which led to the suppression of TNF
      induced activation of c- JNK, p38 MAPK, and p44/p42 MAPK. Jurkat cells that did
      not express Syk (JCaM1, JCaM1/lck) showed lack of TNF-induced Syk, JNK, p38 MAPK,
      and p44/p42 MAPK activation, as well as TNF-induced IkappaBalpha phosphorylation,
      IkappaBalpha degradation, and NF-kappaB activation. TNF-induced NF-kappaB
      activation was enhanced by overexpression of Syk by Syk-cDNA and suppressed when
      Syk expression was down-regulated by expression of Syk-small interfering RNA
      (siRNA-Syk). The apoptotic effects of TNF were reduced by up-regulation of NF
      kappaB by Syk-cDNA, and enhanced by down-regulation of NF-kappaB by siRNA-Syk.
      Immunoprecipitation of cells with Syk Abs showed TNF-dependent association of Syk
      with both TNFR1 and TNFR2; this association was enhanced by up-regulation of Syk
      expression with Syk-cDNA and suppressed by down-regulation of Syk using siRNA
      Syk. Overall, our results demonstrate that Syk activation plays an essential role
      in TNF-induced activation of JNK, p38 MAPK, p44/p42 MAPK, NF-kappaB, and
      apoptosis.

PMID- 15240696
TI  - Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D.
AB  - We characterized two novel members of the RAET1/ULBP gene cluster, RAET1E and
      RAET1G. The encoded proteins were similar to the ULBP in their class I-like
      alpha1 and alpha2 domains, but differed in that, instead of being GPI-anchored,
      their sequences were type 1 membrane-spanning molecules. Both proteins were
      capable of being expressed at the cell surface. Both proteins bound the
      activating receptor NKG2D, and RAET1G bound the human CMV protein UL16. The
      expression of diverse NKG2D-binding molecules in different tissues and with
      different properties is consistent with multiple modes of infection- or stress
      induced activation.

PMID- 15240697
TI  - Dissection of the HLA-DR4 peptide repertoire in endocrine epithelial cells:
      strong influence of invariant chain and HLA-DM expression on the nature of
      ligands.
AB  - Class II MHC (MHC II) expression is restricted to professional APCs and thymic
      epithelium but it also occurs in the epithelial cells of autoimmune organs which
      are the unique targets of the CD4 autoreactive T cells in endocrine autoimmune
      diseases. This specificity is presumably conditioned by an epithelium-specific
      peptide repertoire associated to MHC II at the cell surface. MHC II expression
      and function is dependent on the action of two main chaperones, invariant chain
      (Ii) and DM, whose expression is coregulated with MHC II. However, there is
      limited information about the in vivo expression levels of these molecules and
      uncoordinated expression has been demonstrated in class II-positive epithelial
      cells that may influence the MHC-associated peptide repertoires and the outcome
      of the autoimmune response. We have examined the pool of peptides associated to
      DR4 molecules expressed by a neuroendocrine epithelial cell and the consequences
      of Ii and DM coexpression. The RINm5F rat insulinoma cell line was transfected
      with HLA-DRB1*0401, Ii, and DM molecules in four different combinations: RIN-DR4,
      -DR4Ii, -DR4DM, and -DR4IiDM. The analysis of the peptide repertoire and the
      identification of the DR4 naturally processed ligands in each transfected cell
      were achieved by mass spectrometry. The results demonstrate that 1) the
      expression of Ii and DM affected the DR4 peptide repertoires by producing
      important variations in their content and in the origin of peptides; 2) these
      restrictions affected the stability and sequence of the peptides of each
      repertoire; and 3) Ii and DM had both independent and coordinate effects on these
      repertoires.

PMID- 15240698
TI  - Analysis of transcription factor expression during discrete stages of postnatal
      thymocyte differentiation.
AB  - Postnatal T lymphocyte differentiation in the thymus is a multistage process
      involving serial waves of lineage specification, proliferative expansion, and
      survival/cell death decisions. Although these are believed to originate from
      signals derived from various thymic stromal cells, the ultimate consequence of
      these signals is to induce the transcriptional changes that are definitive of
      each step. To help to characterize this process, high density microarrays were
      used to analyze transcription factor gene expression in RNA derived from
      progenitors at each stage of T lymphopoietic differentiation, and the results
      were validated by a number of appropriate methods. We find a large number of
      transcription factors to be expressed in developing T lymphocytes, including many
      with known roles in the control of differentiation, proliferation, or cell
      survival/death decisions in other cell types. Some of these are expressed
      throughout the developmental process, whereas others change substantially at
      specific developmental transitions. The latter are particularly interesting,
      because stage-specific changes make it increasingly likely that the corresponding
      transcription factors may be involved in stage-specific processes. Overall, the
      data presented here represent a large resource for gene discovery and for
      confirmation of results obtained through other methods.

PMID- 15240699
TI  - STAT1 regulates lipopolysaccharide- and TNF-alpha-dependent expression of
      transporter associated with antigen processing 1 and low molecular mass
      polypeptide 2 genes in macrophages by distinct mechanisms.
AB  - Transporter associated with Ag processing 1 and low molecular mass polypeptide 2
      (LMP2) are essential for class I MHC function and share a common bidirectional
      promoter. In murine bone marrow-derived macrophages, LPS and TNF-alpha induced
      Tap1 and up-regulated Lmp2, which is constitutively expressed at low levels.
      These two genes are induced by LPS and TNF-alpha with distinct kinetics, at 6 and
      12-24 h, respectively. Using macrophages derived from the TNF-alpha receptors of
      knockout mice, we found that induction by LPS is not due to the autocrine
      production of TNF-alpha. In macrophages from STAT-1 knockout mice, neither LPS
      nor TNF-alpha induced the expression of Tap1 or Lmp2. The shared promoter
      contains several areas that can be controlled by STAT-1, such as the proximal and
      distal IFN-gamma activation site (GAS) boxes in the direction of the Tap1 gene.
      By making deletions of the promoter, we determined that only the proximal GAS box
      is required for LPS induction of Tap1 and Lmp2. In contrast, TNF-alpha induction
      of these two genes is dependent on the IFN regulatory factor-1 and NF-kappaB
      boxes, and not on the GAS box. Our experiments using gel shift analysis and Abs
      indicated that STAT1 binds to the GAS box in nuclear extracts from LPS-treated
      macrophages. The nuclear extracts obtained from macrophages treated with TNF
      alpha bound to the IFN regulatory factor-1 and NF-kappaB boxes. These results
      show that LPS and TNF-alpha regulate the induction of Tap1 and Lmp2 through
      STAT1, but use distinct areas of the promoter.

PMID- 15240700
TI  - The E2F-1 transcription factor promotes caspase-8 and bid expression, and
      enhances Fas signaling in T cells.
AB  - The immune system depends on the extensive proliferation of rare Ag-specific
      precursor T lymphocytes, followed by their differentiation, the delivery of
      effector function, and finally death by apoptosis. T cells that lack the E2F-1
      transcription factor, which is activated as cells pass the restriction point and
      enter S phase, show defects in activation-induced cell death. We now report that
      E2F-1 increases the activity of an apoptotic pathway that is important in murine
      primary T cells. Thus, E2F-1 promotes the transcription of Bid, a molecule that
      links death receptor signaling to the activation of apoptotic mechanisms in
      mitochondria. It also promotes the transcription of caspase-8, the enzyme that
      cleaves and activates Bid. Enforced expression of Bid can partially restore
      apoptosis in E2F-1-deficient T cells. Thus, E2F-1 integrates cell cycle
      progression with apoptosis.

PMID- 15240701
TI  - A short consensus repeat-containing complement regulatory protein of lamprey that
      participates in cleavage of lamprey complement 3.
AB  - The prototype of the short consensus repeat (SCR)-containing C regulatory protein
      is of interest in view of its evolutionary significance with regard to the origin
      of the C regulatory system. Lamprey is an agnathan fish that belongs to the
      lowest class of vertebrates. Because it does not possess lymphocytes, it lacks Ig
      and consequently the classical C pathway. We identified an SCR-containing C
      regulatory protein from the lamprey. The primary structure predicted from the
      cDNA sequence showed that this is a secretary protein consisting of eight SCRs.
      This framework is similar to the alpha-chain of C4b-binding protein (C4bp). SCR2
      and -3 of human C4bp are essential for C4b inactivation, and this region is
      fairly well conserved in the lamprey protein. However, the other SCRs of this
      protein are similar to those of other human C regulatory proteins. The lamprey
      protein binds to the previously reported lamprey C3b/C3bi deposited on yeast and
      cleaves lamprey C3b-like C3 together with a putative serum protease. The scheme
      resembles the C regulatory system of mammals, where factor I and its cofactor
      inactivate C3b. Unlike human cofactors, the lamprey protein requires divalent
      cations for C3b-like C3 cleavage. Its artificial membrane-anchored form protects
      host cells from lamprey C attack via the lectin pathway. Thus, the target of this
      protein appears to be C3b and/or its family. We named this protein Lacrep, the
      lamprey C regulatory protein. Lacrep is a member of SCR-containing C regulators,
      the first of its kind identified in the lowest vertebrates.

PMID- 15240702
TI  - Unprecedented multiplicity of Ig transmembrane and secretory mRNA forms in the
      cartilaginous fish.
AB  - In most jawed vertebrates including cartilaginous fish, membrane-bound IgM is
      expressed as a five Ig superfamily (Igsf)-domain H chain attached to a
      transmembrane (Tm) region. Heretofore, bony fish IgM was the one exception with
      IgM mRNA spliced to produce a four-domain Tm H chain. We now demonstrate that the
      Tm and secretory (Sec) mRNAs of the novel cartilaginous fish Ig isotypes, IgW and
      IgNAR, are present in multiple forms, most likely generated by alternative
      splicing. In the nurse shark, Ginglymostoma cirratum, and horn shark,
      Heterodontus francisci, alternative splicing of Tm exons to the second or the
      fourth constant (C(H)) exons produces two distinct IgW Tm cDNAs. Although the
      seven-domain IgW Sec cDNA form contains a canonical secretory tail shared with
      IgM, IgNAR, and IgA, we report a three-domain cDNA form of shark IgW (IgW(short))
      having an unusual Sec tail, which is orthologous to skate IgX(short) cDNA. The
      IgW and IgW(short) Sec transcripts are restricted in their tissue distribution
      and expression levels vary among individual sharks, with all forms expressed
      early in ontogeny. IgNAR mRNA is alternatively spliced to produce a truncated
      four-domain Tm cDNA and a second Tm cDNA is expressed identical in Igsf domains
      as the Sec form. PBL is enriched in the Tm cDNA of these Igs. These molecular
      data suggest that cartilaginous fish have augmented their humoral immune
      repertoire by diversifying the sizes of their Ig isotypes. Furthermore, these Tm
      cDNAs are prototypical and the truncated variants may translate as more stable
      protein at the cell surface.

PMID- 15240703
TI  - Peptide variants of viral CTL epitopes mediate positive selection and emigration
      of Ag-specific thymocytes in vivo.
AB  - During development, thymocytes carrying TCRs mediating low-affinity interactions
      with MHC-bound self-peptides are positively selected for export into the mature
      peripheral T lymphocyte pool. Thus, exogenous administration of certain altered
      peptide ligands (APL) with reduced TCR affinity relative to cognate Ags may
      provide a tool to elicit maturation of desired TCR specificities. To test this
      "thymic vaccination" concept, we designed APL of the viral CTL epitopes gp33-41
      and vesicular stomatitis virus nucleoprotein octapeptide N52-59 relevant for the
      lymphocytic choriomeningitis virus-specific P14- and vesicular stomatitis virus
      specific N15-TCRs, respectively, and examined their effects on thymocytes in vivo
      using irradiation chimeras. Injection of APL into irradiated congenic (Ly-5.1)
      mice, reconstituted with T cell progenitors from the bone marrow of P14 RAG2(-/-)
      (Ly-5.2) or N15 RAG2(-/-) (Ly-5.2) transgenic mice, resulted in positive
      selection of T cells expressing the relevant specificity. Moreover, the variants
      led to export of virus-specific T cells to lymph nodes, but without inducing T
      cell proliferation. These findings show that the mature T cell repertoire can be
      altered by in vivo peptide administration through manipulation of thymic
      selection.

PMID- 15240704
TI  - Tyrosine kinase 2 interacts with and phosphorylates receptor for activated C
      kinase-1, a WD motif-containing protein.
AB  - Receptor for activated C kinase (Rack)-1 is a protein kinase C-interacting
      protein, and contains a WD repeat but has no enzymatic activity. In addition to
      protein kinase C, Rack-1 also binds to Src, phospholipase Cgamma, and ras-GTPase
      activating proteins. Thus, Rack-1 is thought to function as a scaffold protein
      that recruits specific signaling elements. In a cytokine signaling cascade, Rack
      1 has been reported to interact with the IFN-alphabeta receptor and Stat1. In
      addition, we show here that Rack-1 associates with a member of Jak, tyrosine
      kinase 2 (Tyk2). Rack-1 interacts weakly with the kinase domain and interacts
      strongly with the pseudokinase domain of Tyk2. Rack-1 associates with Tyk2 via
      two regions, one in the N terminus and one in the middle portion (aa 138-203) of
      Rack-1. Jak activation causes the phosphorylation of tyrosine 194 on Rack-1.
      After phosphorylation, Rack-1 is translocated toward the perinuclear region. In
      addition to functioning as a scaffolding protein, these results raise the
      possibility that Rack-1 functions as a signaling molecule in cytokine signaling
      cascades.

PMID- 15240705
TI  - Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation.
AB  - We have identified two intronic regions of mouse prdm1, the gene encoding B
      lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional
      repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is
      conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro
      and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo.
      Neither Bcl-6 response element functions as a STAT3-response element, showing
      that STAT3 does not compete with Bcl-6 at these sites. Bcl-6(-/-) mice confirm
      the biological importance of Bcl-6-dependent repression of prdm1. These mice have
      elevated Ab response, increased Ig-secreting cells, and increased Blimp-1(+)
      cells in spleen following immunization and their splenic B cells show accelerated
      plasmacytic development in vitro.

PMID- 15240706
TI  - TLR4 is the signaling but not the lipopolysaccharide uptake receptor.
AB  - TLR4 is the primary recognition molecule for inflammatory responses initiated by
      bacterial LPS (endotoxin). Internalization of endotoxin by various cell types is
      an important step for its removal and detoxification. Because of its role as an
      LPS-signaling receptor, TLR4 has been suggested to be involved in cellular LPS
      uptake as well. LPS uptake was investigated in primary monocytes and endothelial
      cells derived from TLR4 and CD14 knockout C57BL/6 mice using tritiated and
      fluorescein-labeled LPS. Intracellular LPS distribution was investigated by
      deconvolution confocal microscopy. We could not observe any difference in LPS
      uptake and intracellular LPS distribution in either monocytes or endothelial
      cells between TLR4(-/-) and wild-type cells. As expected, CD14(-/-) monocytes
      showed a highly impaired LPS uptake, confirming CD14-dependent uptake in
      monocytes. Upon longer incubation periods, the CD14-deficient monocytes mimicked
      the LPS uptake pattern of endothelial cells. Endothelial cell LPS uptake is
      slower than monocyte uptake, LBP rather than CD14 dependent, and sensitive to
      polyanionic polymers, which have been shown to block scavenger receptor-dependent
      uptake mechanisms. We conclude that TLR4 is not involved in cellular LPS uptake
      mechanisms. In membrane CD14-positive cells, LPS is predominantly taken up via
      CD14-mediated pathways, whereas in the CD14-negative endothelial cells, there is
      a role for scavenger receptor-dependent pathways.

PMID- 15240707
TI  - Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of
      the p28 subunit of IL-27.
AB  - IL-27 is a recently defined family member of the long-chain four-helix bundle
      cytokines, which consists of EBI3, an IL-12p40-related protein, and p28, an IL
      12p35-related polypeptide. The role of IL-27 in the regulation of inflammatory
      autoimmune diseases has never been studied. The current study uses the DNA
      vaccination technology, and highly specific Abs to the p28 subunit of IL-27 that
      were generated by this technology, to delineate its role in the regulation of
      adjuvant-induced arthritis in Lewis rats. Neutralizing the in vivo function of IL
      27 by targeted DNA vaccines and by Abs against IL-27 p28 that were produced in
      protected donors could rapidly suppress an ongoing disease. Disease suppression
      was associated with a reduced ex vivo production of inflammatory cytokines. We
      then used these Abs to investigate the mechanistic basis of disease suppression,
      showing that IL-27 is not only involved in directing the polarization of naive T
      cells, but also affects the proliferative response and cytokine production of Ag
      specific effector/memory Th1 cells. This may explain, in part, its important role
      in the regulation of inflammatory autoimmune diseases, and also suggest novel
      ways of therapy.

PMID- 15240708
TI  - TLR9 is localized in the endoplasmic reticulum prior to stimulation.
AB  - In mammals, 10 TLRs recognize conserved pathogen-associated molecular patterns,
      resulting in the induction of inflammatory innate immune responses. One of these,
      TLR9, is activated intracellularly by bacterial DNA and synthetic
      oligodeoxynucleotides (ODN), containing unmethylated CpG dinucleotides. Following
      treatment with CpG ODN, TLR9 is found in lysosome-associated membrane protein
      type 1-positive lysosomes, and we asked which intracellular compartment contains
      TLR9 before CpG exposure. Surprisingly, we found by microscopy and supporting
      biochemical evidence that both transfected and endogenously expressed human TLR9
      is retained in the endoplasmic reticulum. By contrast, human TLR4 trafficked to
      the cell surface, indicating that endoplasmic reticulum retention is not a
      property common to all TLRs. Because TLR9 is observed in endocytic vesicles
      following exposure to CpG ODN, our data indicate that a special mechanism must
      exist for translocating TLR9 to the signaling compartments that contain the CpG
      DNA.

PMID- 15240710
TI  - Engagement of the pathogen survival response used by group A Streptococcus to
      avert destruction by innate host defense.
AB  - Neutrophils are a critical component of human innate host defense and efficiently
      kill the vast majority of invading microorganisms. However, bacterial pathogens
      such as group A Streptococcus (GAS) successfully avert destruction by neutrophils
      to cause human infections. Relatively little is known about how pathogens detect
      components of the innate immune system to respond and survive within the host. In
      this study, we show that inactivation of a two-component gene regulatory system
      designated Ihk-Irr significantly attenuates streptococcal virulence in mouse
      models of soft tissue infection and bacteremia. Microarray analysis of wild-type
      and irr-negative mutant (irr mutant) GAS strains revealed that Ihk-Irr influenced
      expression of 20% of all transcripts in the pathogen genome. Notably, at least 11
      genes involved in cell wall synthesis, turnover, and/or modification were down
      regulated in the irr mutant strain. Compared with the wild-type strain,
      significantly more of the irr mutant strain was killed by human neutrophil
      components that destroy bacteria by targeting the cell envelope (cell wall and/or
      membrane). Unexpectedly, expression of ihk and irr was dramatically increased in
      the wild-type strain exposed to these same neutrophil products under conditions
      that favored cell envelope damage. We report a GAS mechanism for detection of
      innate host defense that initiates the pathogen survival response, in which cell
      wall synthesis is critical. Importantly, our studies identify specific genes in
      the pathogen survival response as potential targets to control human infections.

PMID- 15240709
TI  - Role of IFN regulatory factor-1 and IL-12 in immunological resistance to
      pathogenesis of N-methyl-N-nitrosourea-induced T lymphoma.
AB  - IFN regulatory factor-1 (IRF-1) is a critical effector molecule in IFN signaling
      and acts as a tumor suppressor and tumor susceptibility gene. IL-12 is a key
      factor in the induction of innate resistance and generation of Th1 cells and CTL.
      Our recent study has revealed an intimate relationship between IRF-1 and IL-12 in
      that IRF-1 regulates the production of IL-12 by selectively controlling
      transcriptional activation of IL-12 p35 gene. In this work, we find that IRF-1
      deficient mice are highly susceptible to N-methyl-N-nitrosourea (MNU)-induced T
      lymphomas. This susceptibility is associated with strong defects in the
      expression of IL-12, lymphotoxin (LT)beta, and IFN-gamma. Consistently, IL-12
      p35(-/-), IFN-gamma(-/-), and LTbeta(-/-) mice are also highly vulnerable to MNU
      induced carcinogenesis. Administration of rIL-12 to IRF-1(-/-) mice restores
      normal expression of LTbeta and IFN-gamma, and significantly enhances the ability
      of IRF-1(-/-) mice to resist MNU-induced pathogenesis. This strongly suggests an
      IRF-1/IL-12/IFN-gamma regulatory axis in tumor surveillance. By DNA microarray
      analysis, we comprehensively identify differences and patterns in gene expression
      in splenocytes of wild-type (WT) vs IRF-1(-/-) mice challenged with MNU. This
      study contributes to efforts to elucidate the cellular/molecular mechanisms and
      the downstream players involved in IRF-1-mediated host defense against
      lymphoproliferative malignancies.

PMID- 15240711
TI  - Secretion of intracellular IL-1 receptor antagonist (type 1) is dependent on P2X7
      receptor activation.
AB  - Inflammatory mechanisms are critical in the arterial response to injury. Both IL
      1 and the naturally occurring inhibitor of IL-1, IL-1R antagonist (IL-1ra), are
      expressed in the arterial wall, and in particular in the endothelium. Previous
      studies suggest that endothelial cells only make the intracellular type I isoform
      of IL-1ra (icIL-1ra1), an isoform known to lack a secretory signal peptide. It is
      unclear how icIL-1ra is released from the endothelial cell to act as an
      antagonist on cell surface IL-1 type I receptors. IL-1beta, which also lacks a
      secretory signal peptide, may be released by ATP stimulation of the P2X(7)R.
      Therefore, we examined whether icIL-1ra1 release occurs in an analogous manner,
      using both the mouse macrophage cell line RAW264.7 and HUVECs. P2X(7)R activation
      caused icIL-1ra1 release from LPS-primed RAW264.7 macrophages and from HUVECs.
      This release was inhibited in the absence of extracellular calcium, and
      attenuated by preincubation with oxidized ATP, KN62, and apyrase. Endogenous ATP
      release, which also facilitated release of icIL-1ra1, was detected during LPS
      treatment of both RAW264.7 macrophages and HUVECs. Annexin V assays showed that
      ATP stimulation resulted in a rapid phosphatidylserine (PS) exposure on the cell
      surface of RAW264.7 macrophages, and that PS-exposed microvesicles contained icIL
      1ra1. However, PS flip and microvesicle shedding was not apparent in ATP-treated
      HUVECs. These data support a general role for the P2X(7)R in the release of
      leaderless cytokines into the extracellular medium, and indicate how icIL-1ra1
      may act upon its extracellular target, the IL-1R.

PMID- 15240712
TI  - Activation, differentiation, and migration of naive virus-specific CD8+ T cells
      during pulmonary influenza virus infection.
AB  - The low precursor frequency of individual virus-specific CD8(+) T cells in a
      naive host makes the early events of CD8(+) T cell activation, proliferation, and
      differentiation in response to viral infection a challenge to identify. We have
      therefore examined the response of naive CD8(+) T cells to pulmonary influenza
      virus infection with a murine adoptive transfer model using hemagglutinin
      specific TCR transgenic CD8(+) T cells. Initial activation of CD8(+) T cells
      occurs during the first 3 days postinfection exclusively within the draining
      lymph nodes. Acquisition of CTL effector functions, including effector cytokine
      and granule-associated protease expression, occurs in the draining lymph nodes
      and differentially correlates with cell division. Division of activated CD8(+) T
      cells within the draining lymph nodes occurs in an asynchronous manner between
      days 3 and 4 postinfection. Despite the presence of Ag for several days within
      the draining lymph nodes, dividing T cells do not appear to maintain contact with
      residual Ag. After multiple cell divisions, CD8(+) T cells exit the draining
      lymph nodes and migrate to the infected lung. Activated CD8(+) T cells also
      disseminate throughout lymphoid tissue including the spleen and distal lymph
      nodes following their emigration from draining lymph nodes. These results
      demonstrate an important role for draining lymph nodes in orchestrating T cell
      responses during a local infection of a discrete organ to generate effector
      CD8(+) T cells capable of responding to infection and seeding peripheral lymphoid
      tissues.

PMID- 15240713
TI  - Microbial DNA induces a host defense reaction of human respiratory epithelial
      cells.
AB  - Epithelial cells represent the initial site of bacterial colonization in the
      respiratory tract. TLR9 has been identified in B cells and CD 123(+) dendritic
      cells and found to be involved in the recognition of microbial DNA. It was the
      aim of the study to investigate the role of TLR9 in the host defense reactions of
      the respiratory epithelium. Respiratory epithelial cell lines (IHAEo(-), Calu-3)
      or fully differentiated primary human cells as air-liquid interface cultures were
      stimulated with bacterial DNA or synthetic oligonucleotides containing CpG motifs
      (CpG oligodeoxynucleotides). Expression of TLR9, cytokines, and human beta
      defensin 2 was determined by quantitative RT-PCR or by ELISA. We found that TLR9
      is expressed by respiratory epithelial cell lines and fully differentiated
      primary epithelial cells at low levels. Stimulation of the above-mentioned cells
      with bacterial DNA or CpG oligodeoxynucleotide resulted in an inflammatory
      reaction characterized by a dose-dependent up-regulation of cytokines (IL-6, IL
      8) and human beta-defensin 2. Up-regulation of NF-kappaB in epithelial cells in
      response to the CpG motif containing DNA was inhibited by overexpression of a
      dominant negative form of MyD88. These results provide clear evidence that the
      human respiratory epithelium is capable of detecting microbial DNA by TLR9. The
      respiratory epithelium has an important function in triggering innate immune
      responses and therefore represents an interesting target for anti-inflammatory
      therapy.

PMID- 15240714
TI  - CD25+CD4+ cells contribute to Th2 polarization during helminth infection by
      suppressing Th1 response development.
AB  - Mice infected with Schistosoma mansoni develop polarized Th2 responses in which
      Th1 responses are prevented by IL-10-mediated suppression of IL-12 production. We
      show that dendritic cells from infected mice are primed to make IL-12 in response
      to CD40 ligation, and that IL-10 acts by inhibiting this process. In infected
      mice, two subpopulations of CD4(+) cells, separable by their expression of CD25,
      make IL-10. CD25(+)CD4(+) cells expressed forkhead box P3, inhibited
      proliferation of CD4(+) T cells, and made IL-10, but little IL-5. In contrast,
      CD25(-)CD4(+) cells failed to express forkhead box P3 or to inhibit proliferation
      and accounted for all the IL-5, IL-6, and IL-13 produced by unseparated splenic
      populations. Thus, CD25(+) and CD25(-) subpopulations could be characterized as
      regulatory T cells (Treg cells) and Th2 cells, respectively. Consistent with
      their ability to make IL-10, both CD25(+) and CD25(-)CD4(+) T cells from infected
      mice were able, when stimulated with egg Ag, to suppress IL-12 production by CD40
      agonist-stimulated dendritic cells. Additionally, in adoptive transfer
      experiments, both CD4(+) subpopulations of cells were able to partially inhibit
      the development of Th1 responses in egg-immunized IL-10(-/-) mice. The
      relationship of Treg cells in infected mice to natural Treg cells was strongly
      suggested by the ability of CD25(+)CD4(+) cells from naive mice to inhibit Th1
      response development when transferred into egg-immunized or infected IL-10(-/-)
      mice. The data suggest that natural Treg cells and, to a lesser extent, Th2 cells
      play roles in suppressing Th1 responses and ensuring Th2 polarization during
      schistosomiasis.

PMID- 15240715
TI  - CD154 signaling regulates the Th1 response to herpes simplex virus-1 and
      inflammation in infected corneas.
AB  - Approximately 7 days after HSV-1 corneal infection, BALB/c mice develop tissue
      destructive inflammation in the cornea termed herpes stromal keratitis (HSK), as
      well as periocular skin lesions that are characterized by vesicles, edema, and
      fur loss. CD4(+) T cells and Th1 cytokines contribute to both the immunopathology
      in the cornea and the eradication of viral replication in the skin. We
      demonstrate that disruption of CD40/CD154 signaling does not impact the initial
      expansion of CD4(+) T cells in the draining lymph nodes, but dramatically reduces
      the persistence and Th1 polarization of these cells. Despite the reduced Th1
      response, CD154(-/-) mice developed HSK and periocular skin disease with similar
      kinetics and severity (as assessed by clinical examination) as wild-type (WT)
      mice. However, when the composition of the inflammatory infiltrate was examined
      by flow cytometric analysis, CD154(-/-) mice exhibited significantly fewer CD4(+)
      and CD8(+) T cells and neutrophils than WT mice at the peak of HSK. Moreover,
      CD4(+) T cells from infected corneas of CD154(-/-) mice produced significantly
      less IFN-gamma than those of WT mice when stimulated with viral Ags in vitro. The
      IFN-gamma production of cells from infected corneas of WT mice was not affected
      by addition of anti-CD154 mAb to the stimulation cultures. This suggests that
      CD154 signaling is required at the inductive phase, but not at the effector
      phase, of the Th1 response within the infected cornea. We conclude that local
      disruption of CD40/CD154 signaling is not likely to be a useful therapy for HSK.

PMID- 15240716
TI  - Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of
      programmed death ligand 1 on macrophages.
AB  - Infectious pathogens can selectively stimulate activation or suppression of T
      cells to facilitate their survival within humans. In this study we demonstrate
      that the trematode parasite Schistosoma mansoni has evolved with two distinct
      mechanisms to suppress T cell activation. During the initial 4- to 12-wk acute
      stages of a worm infection both CD4(+) and CD8(+) T cells are anergized. In
      contrast, infection with male and female worms induced T cell anergy at 4 wk,
      which was replaced after egg laying by T cell suppression via a known NO
      dependent mechanism, that was detected for up to 40 wk after infection. Worm
      induced anergy was mediated by splenic F4/80(+) macrophages (Mphi) via an IL-4-,
      IL-13-, IL-10-, TGF-beta-, and NO-independent, but cell contact-dependent,
      mechanism. F4/80(+) Mphi isolated from worm-infected mice were shown to induce
      anergy of naive T cells in vitro. Furthermore, naive Mphi exposed to live worms
      in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in
      vitro worm-modulated Mphi revealed that of the family of B7 costimulatory
      molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated.
      The addition of inhibitory mAb against PD-L1, but not PD-L2, to worm-modulated
      Mphi completely blocked the ability of these cells to anergize T cells. These
      data highlight a novel mechanism through which S. mansoni worms have usurped the
      natural function of PD-L1 to reduce T cell activation during early acute stages
      of infection before the subsequent emergence of egg-induced T cell suppression in
      the chronic stages of infection.

PMID- 15240717
TI  - Human dendritic cells respond to Helicobacter pylori, promoting NK cell and Th1
      effector responses in vitro.
AB  - Helicobacter pylori infection leads to chronic gastric inflammation. The current
      study determined the response of human APCs, NK cells, and T cells toward the
      bacteria in vitro. Human monocyte-derived dendritic cells (DC) were incubated
      with bacteria for 48 h. Intact H. pylori at a multitude of infection 5 stimulated
      the expression of MHC class II (4- to 7-fold), CD80, and CD86 B7 molecules (10-
      to 12-fold) and the CD83 costimulatory molecule (>30-fold) as well as IL-12
      secretion (>50-fold) in DCs, and thereby, strongly induced their maturation and
      activation. CD56(+)/CD4(-) NK cells, as well as CD4(+)/CD45RA(+) naive T cells,
      were isolated and incubated with DCs pulsed with intact bacteria or different
      cellular fractions. Coculture of H. pylori-pulsed DCs with NK cells strongly
      potentiated the secretion of TNF-alpha and IFN-gamma. Coculture of naive T cells
      with H. pylori-pulsed DCs significantly enhanced TNF-alpha, IFN-gamma, and IL-2
      secretion as well as T-bet mRNA levels, while GATA-3 mRNA was lowered. However,
      the effect appeared attenuated compared with coculture with Escherichia coli. A
      greater stimulation was seen with naive T cells and DCs pulsed with H. pylori
      membrane preparations. Intact H. pylori potently induced the maturation and
      activation of human monocyte-derived DC and thereby promote NK and Th1 effector
      responses. The strong activation of NK cells may be important for the innate
      immune response. Th1-polarized T cells were induced especially by incubation with
      membrane preparations of H. pylori, suggesting that membrane proteins may account
      for the specific adaptive immune response.

PMID- 15240718
TI  - Fluid shear regulates the kinetics and receptor specificity of Staphylococcus
      aureus binding to activated platelets.
AB  - The interaction between surface components on the invading pathogen and host
      cells such as platelets plays a key role in the regulation of endovascular
      infections. However, the mechanisms mediating Staphylococcus aureus binding to
      platelets under shear remain largely unknown. This study was designed to
      investigate the kinetics and molecular requirements of platelet-S. aureus
      interactions in bulk suspensions subjected to a uniform shear field. Hydrodynamic
      shear-induced collisions augment platelet-S. aureus binding, which is further
      potentiated by platelet activation with stromal derived factor-1beta. Peak
      adhesion efficiency occurs at low shear (100 s(-1)) and decreases with increasing
      shear. The molecular interaction of platelet alpha(IIb)beta(3) with bacterial
      clumping factor A through fibrinogen bridging is necessary for stable bacterial
      binding to activated platelets under shear. Although this pathway is sufficient
      at low shear (</=400 s(-1)), the involvement of platelet gpIb and staphylococcal
      protein A through von Willebrand factor bridging is essential for optimal
      recruitment of S. aureus cells by platelets in the high shear regime. IgG plays
      an inhibitory role in the adhesion process, presumably by interfering with the
      binding of von Willebrand factor to staphylococcal protein A. This study
      demonstrates that platelet activation and a fluid-mechanical environment
      representative of the vasculature affect platelet-S. aureus cell-adhesive
      interactions pertinent to the process of S. aureus-induced bloodstream
      infections.

PMID- 15240719
TI  - Type I IFN protects permissive macrophages from Legionella pneumophila infection
      through an IFN-gamma-independent pathway.
AB  - Legionella pneumophila is an intracellular pathogen whose replication in
      macrophages is mainly controlled by IFN-gamma. Freshly isolated peritoneal
      macrophages elicited in vivo with thioglycolate (TG) from A/J mice are highly
      permissive to L. pneumophila growth in vitro, while TG-elicited macrophages from
      CD1 mice are resistant. In this study, we show that when CD1 TG-macrophages are
      cultured for 7 days, they become permissive to Legionella infection. We
      demonstrate that treatment with type I IFN (IFN-alphabeta) totally inhibits the
      growth of L. pneumophila in both freshly isolated A/J and in vitro-aged CD1 TG
      macrophages. IFN-alphabeta protective effect on permissive macrophages was
      comparable to that induced by IFN-gamma. Even low doses of either IFN-alpha or
      IFN-beta alone were effective in inhibiting L. pneumophila multiplication in
      macrophage cultures. Notably, treatment of resistant, freshly isolated CD1 TG
      macrophages with Ab to mouse IFN-alphabeta significantly enhanced their
      susceptibility to Legionella infection in vitro, thus implying a role of
      endogenous IFN-alphabeta in mediating the natural resistance of macrophages to L.
      pneumophila infection. Finally, addition of anti-IFN-gamma-neutralizing Ab did
      not restore Legionella growth in IFN-alpha- or IFN-beta-treated A/J or CD1
      permissive macrophages, indicating that IFN-alphabeta effect was not mediated by
      IFN-gamma. This observation was further confirmed by the finding that IFN
      alphabeta was effective in inhibiting L. pneumophila replication in macrophages
      from IFN-gamma receptor-deficient mice. Taken together, our results provide the
      first evidence for a role of IFN-alphabeta in the control of L. pneumophila
      infection in mouse models of susceptible macrophages and suggest the existence of
      different pathways for the control of intracellular bacteria in macrophages.

PMID- 15240720
TI  - Inhibition of farnesyltransferase prevents collagen-induced arthritis by down
      regulation of inflammatory gene expression through suppression of p21(ras)
      dependent NF-kappaB activation.
AB  - Farnesylation of p21(ras) is an important step in the intracellular signaling
      pathway of growth factors, hormones, and immune stimulants. We synthesized a
      potent and selective farnesyltransferase inhibitor (LB42708) with IC(50) values
      of 0.8 nM in vitro and 8 nM in cultured cells against p21(ras) farnesylation and
      examined the effects of this inhibitor in the settings of inflammation and
      arthritis. LB42708 suppressed NF-kappaB activation and iNOS promoter activity by
      suppressing the I-kappaB kinase activity and I-kappaBalpha degradation. The
      inhibitor suppressed the expression of inducible NO synthase, cyclooxygenase-2,
      TNF-alpha, and IL-1beta and the production of NO and PGE(2) in immune-activated
      macrophages and osteoblasts as well as LPS-administrated mice. Furthermore, in
      vivo administration of LB42708 significantly decreased the incidence and severity
      of arthritis as well as mRNA expression of inducible NO synthase, cyclooxygenase
      2, TNF-alpha, and IL-1beta in the paws of collagen-induced arthritic mice
      compared with controls. These observations indicate that the anti-inflammatory
      and antiarthritic effects of the farnesyltransferase inhibitor may be ascribed to
      the inhibition of I-kappaB kinase activity and subsequent suppression of NF
      kappaB-dependent inflammatory gene expression through the suppression of p21(ras)
      farnesylation. Together, these findings reveal that the inhibitory effect of
      LB42708 on p21(ras)-dependent NF-kappaB activation may have potential therapeutic
      value for arthritis and other inflammatory diseases.

PMID- 15240721
TI  - The lectin-like domain of complement receptor 3 protects endothelial barrier
      function from activated neutrophils.
AB  - The adhesion of neutrophils to endothelial cells is a central event leading to
      diapedesis and involves the binding of the I-domain of beta(2) integrins
      (CD11/CD18) to endothelial ICAMs. In addition to the I-domain, the beta(2)
      integrin complement receptor 3 (CR3) (CD11b/CD18) contains a lectin-like domain
      (LLD) that can alter leukocyte functions such as chemotaxis and cytotoxicity. The
      present study demonstrates that, in contrast to the CR3 I-domain, Ab blockade of
      the CR3 LLD has no role in mediating neutrophil-induced loss of endothelial
      barrier function. However, activation of CR3 with the LLD agonist beta-glucan
      protects the barrier function of endothelial cells in the presence of activated
      neutrophils and reduces transendothelial migration without affecting adhesion of
      the neutrophils to the endothelium. The LLD site-specific mAb VIM12 obviates beta
      glucan protection while activation of the LLD by VIM12 cross-linking mimics the
      beta-glucan response by both preserving endothelial barrier function and reducing
      neutrophil transendothelial migration. beta-glucan has no direct effect on
      endothelial cell function in the absence of activated neutrophils. These findings
      demonstrate that signaling through the CR3 LLD prevents neutrophil-induced loss
      of endothelial barrier function and reduces diapedesis. This suggests that the
      LLD may be a suitable target for oligosaccharide-based anti-inflammatory
      therapeutics.

PMID- 15240722
TI  - Differential induction of IL-1beta and TNF by CD40 ligand or cellular contact
      with stimulated T cells depends on the maturation stage of human monocytes.
AB  - Cellular contact with stimulated T cells potently induces cytokine production in
      monocytes, a mechanism that is likely to be relevant to chronic inflammation.
      Although the identity of surface molecules involved in this process remains
      elusive, CD40 and its ligand, CD40L, are thought to be implicated, considering
      that they are expressed at the inflammatory site. To ascertain the involvement of
      CD40L, we compared the activation of three different types of human monocytic
      cells, i.e., freshly isolated monocytes, monocytes primed with IFN-gamma (IFN
      gamma-macrophages), and THP-1 cells. These cells were activated by either
      membranes isolated from stimulated T cells (HUT-78 or T lymphocytes) to mimic
      cellular contact, soluble extracts from isolated membranes, or CD40L trimer
      (CD40LT). The production of TNF and IL-1beta was induced by membranes of
      stimulated T cells in the three types of target cells, whereas CD40LT induced TNF
      production in IFN-gamma-macrophages only. Similar results were obtained with
      soluble extracts of T cell membranes, demonstrating that the difference between
      membranes and CD40LT was not due to the particulate form of membranes. CD40LT
      induced neither transcript nor protein of cytokines in monocytes, whereas in IFN
      gamma-macrophages, IL-1beta and TNF mRNA were observed, but only TNF was measured
      in cell supernatants. Finally, anti-CD40L Abs failed to inhibit TNF and IL-1beta
      production induced in IFN-gamma-macrophages by solubilized membranes, whereas TNF
      production induced by CD40LT was inhibited. These results demonstrate that CD40L
      is not required in monocyte activation by direct cellular contact with stimulated
      T cells, although soluble CD40LT induces the production of TNF in IFN-gamma
      macrophages.

PMID- 15240723
TI  - Induction and maintenance of airway responsiveness to allergen challenge are
      determined at the age of initial sensitization.
AB  - Age is an important factor in determining the quantity and quality of immune
      responses when challenged with allergen. In a model of allergen-induced airway
      hyperresponsiveness and inflammation, where the sensitization phase and challenge
      phases can be dissociated in time, we examined the impact of age on these two
      phases. Sensitization of young mice (1-20 wk), but not older animals (30-40 wk),
      led to the development of airway hyperresponsiveness, airway eosinophilia, Th2
      cytokine responses, and allergen-specific IgE, regardless of the age when the
      challenge phase was conducted. Thus, age at the time of initial sensitization was
      shown to be the critical factor dictating the nature of the response to later
      allergen challenge, as older mice remained responsive to allergen challenge if
      sensitized at a young age. These effects were shown to be mediated by lung T
      cells from sensitized young mice. Moreover, the failure of old sensitized mice to
      mediate these effects was shown not to be the result of active suppression of the
      responses. These data define the importance of age at initial allergen exposure
      in dictating subsequent responses in the lung when exposed to allergen and may
      help to define why asthma, even in adults, is most often initiated in early
      childhood.

PMID- 15240724
TI  - Pneumolysin-induced lung injury is independent of leukocyte trafficking into the
      alveolar space.
AB  - Pneumolysin (PLY) is a major virulence factor released by Streptococcus
      pneumoniae and has been implicated in the pathogenesis of pneumococcal pneumonia.
      In this study, we evaluated the contribution of newly recruited neutrophils and
      monocytes and resident alveolar macrophages to the pathogenesis of PLY-induced
      lung injury. Mice received either adhesion-blocking Abs to inhibit alveolar
      leukocyte trafficking or liposomal clodronate to deplete alveolar macrophages
      before intratracheal application of native PLY or its noncytotoxic derivative
      PdB. We found that treatment with PLY but not PdB resulted in increased lung
      vascular permeability. In addition, PLY also induced a decrease in the resident
      alveolar macrophage population, and the recruitment of peripheral blood
      neutrophils and monocytes into the alveolar space. Blockade of PLY-induced
      alveolar leukocyte trafficking by pretreatment of mice with anti-CD18 plus anti
      CD49d Abs or depletion of circulating neutrophils did not attenuate the increase
      in lung permeability observed in response to intratracheal PLY. In addition,
      depletion of resident alveolar macrophages with clodronated liposomes did not
      reduce alveolar injury developing in response to PLY. PLY-induced lung injury was
      associated with only a small increase in bronchoalveolar lavage concentrations of
      cytokines. These data indicate that PLY-induced lung injury results from direct
      pneumotoxic effects on the alveolar-capillary barrier and is independent of both
      resident and recruited phagocytic cells.

PMID- 15240725
TI  - TNF-induced beta2 integrin activation involves Src kinases and a redox-regulated
      activation of p38 MAPK.
AB  - We previously demonstrated that the TNF-alpha-induced inside-out signaling
      leading to beta(2) integrin activation is redox regulated. To identify kinases
      involved in this pathway, the effects of kinase inhibitors on the expression of
      beta(2) integrin activation neoepitope (clone 24) were investigated. We show that
      both p38 MAPK (inhibited by SB203580) and Src kinases (inhibited by PP2) are
      involved in beta(2) integrin activation by TNF and oxidants in human neutrophils.
      Src kinases appeared constitutively active in resting neutrophils and not further
      activated by TNF or oxidants in nonadherent conditions. However, PP2 blocked both
      TNF-induced expression of the 24 epitope and cell adhesion promoted by the
      integrin activating anti-CD18 KIM185 mAb, showing that both the inside-out and
      the outside-in signaling involve Src kinases. p38 MAPK was activated by TNF and
      oxidants in nonadherent conditions i.e., with 10 mM EDTA. This activation in EDTA
      resulted in CD11b, CD35 and CD66 up-regulation and in an oxidative response, all
      blocked by SB203580 and PP2. p38 MAPK was not activated upon direct integrin
      activation by KIM185 mAb. Thus, p38 activation allows the study to distinguish
      the initial transduction pathway leading to beta(2) integrin activation from the
      signaling resulting from integrin engagement. Finally, p38 MAPK activation by TNF
      was blocked by diphenylene iodonium, an inhibitor of flavoprotein oxidoreductase,
      and by the free radical scavenger N-acetylcystein. Taken together, these results
      demonstrate, for the first time, that constitutively activated Src tyrosine
      kinases and a redox-regulated activation of p38 MAPK are involved in TNF inside
      out signaling leading to beta(2) integrin activation.

PMID- 15240726
TI  - E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2
      in acute cutaneous inflammation.
AB  - PGs are derived from arachidonic acid by PG-endoperoxide synthase (PTGS)-1 and
      PTGS2. Although enhanced levels of PGs are present during acute and chronic
      inflammation, a functional role for prostanoids in inflammation has not been
      clearly defined. Using a series of genetically engineered mice, we find that
      PTGS1 has the capacity to induce acute inflammation, but PTGS2 has negligible
      effects on the initiation of this response. Furthermore, we show that the
      contribution of PTGS1 is mediated by PGE(2) acting through the E-prostanoid (EP)3
      receptor. Moreover, in the absence of EP3 receptors, inflammation is markedly
      attenuated, and the addition of nonsteroidal anti-inflammatory agents does not
      further impair the response. These studies demonstrate that PGE(2) promotes acute
      inflammation by activating EP3 receptors and suggest that EP3 receptors may be
      useful targets for anti-inflammatory therapy.

PMID- 15240727
TI  - Immunoregulatory role of nitric oxide in Kilham rat virus-induced autoimmune
      diabetes in DR-BB rats.
AB  - Macrophages play a critical role in the pathogenesis of Kilham rat virus (KRV)
      induced autoimmune diabetes in diabetes-resistant BioBreeding (DR-BB) rats. This
      investigation was initiated to determine the role of macrophage-derived soluble
      mediators, particularly NO, in the pathogenesis of KRV-induced diabetes in DR-BB
      rats. We found that the expression of inducible NO synthase (iNOS), an enzyme
      responsible for NO production, was significantly increased during the early phase
      of KRV infection. Inhibition of iNOS by aminoguanidine (AG) treatment resulted in
      the prevention of diabetes in KRV-infected animals. The expression of IL-1beta,
      TNF-alpha, and IL-12 was significantly decreased in the spleen of AG-treated, KRV
      infected DR-BB rats compared with PBS-treated, KRV-infected control rats.
      Subsequent experiments revealed that AG treatment exerted its preventive effect
      in KRV-infected rats by maintaining the finely tuned immune balance normally
      disrupted by KRV, evidenced by a significant decrease in the expression of IFN
      gamma, but not IL-4, and a decrease in Th1-type chemokine receptors CCR5, CXCR3,
      and CXCR4. We also found that iNOS inhibition by AG decreased the KRV-induced
      expression of MHC class II molecules and IL-2R alpha-chain, resulting in the
      suppression of T cell activation, evidenced by the decreased cytolytic activity
      of CD8(+) T cells. We conclude that NO plays a critical immunoregulatory role by
      up-regulating macrophage-derived proinflammatory cytokines, up-regulating the Th1
      immune response, and activating T cells, leading to type 1 diabetes after KRV
      infection, whereas suppression of NO production by AG treatment prevents KRV
      induced autoimmune diabetes in DR-BB rats.

PMID- 15240728
TI  - Regulation of endotoxin-induced proinflammatory activation in human coronary
      artery cells: expression of functional membrane-bound CD14 by human coronary
      artery smooth muscle cells.
AB  - Low-level endotoxemia has been identified as a powerful risk factor for
      atherosclerosis. However, little is known about the mechanisms that regulate
      endotoxin responsiveness in vascular cells. We conducted experiments to compare
      the relative responses of human coronary artery endothelial cells (HCAEC) and
      smooth muscle cells (HCASMC) to very low levels of endotoxin, and to elucidate
      the mechanisms that regulate endotoxin responsiveness in vascular cells.
      Endotoxin (</=1 ng/ml) caused production of chemotactic cytokines in HCAEC.
      Endotoxin-induced cytokine production was maximal at LPS-binding protein:soluble
      CD14 ratios <1, typically observed in individuals with subclinical infection;
      higher LPS-binding protein:soluble CD14 ratios were inhibitory. Endotoxin
      potently activated HCASMC, with cytokine release >10-fold higher in magnitude at
      >10-fold lower threshold concentrations (10-30 pg/ml) compared with HCAEC. This
      remarkable sensitivity of HCASMC to very low endotoxin concentrations, comparable
      to that found in circulating monocytes, was not due to differential expression of
      TLR4, which was detected in HCAEC, HCASMC, and intact coronary arteries.
      Surprisingly, membrane-bound CD14 was detected in seven different lines of
      HCASMC, conferring responsiveness to endotoxin and to lipoteichoic acid, a
      product of Gram-positive bacteria, in these cells. These results suggest that the
      low levels of endotoxin associated with increased risk for atherosclerosis are
      sufficient to produce inflammatory responses in coronary artery cells. Because
      CD14 recognizes a diverse array of inflammatory mediators and functions as a
      pattern recognition molecule in inflammatory cells, expression of membrane-bound
      CD14 in HCASMC implies a potentially broader role for these cells in transducing
      innate immune responses in the vasculature.

PMID- 15240729
TI  - Antineuroinflammatory effect of NF-kappaB essential modifier-binding domain
      peptides in the adoptive transfer model of experimental allergic
      encephalomyelitis.
AB  - It has been shown that peptides corresponding to the NF-kappaB essential modifier
      binding domain (NBD) of IkappaB kinase alpha or IkappaB kinase beta specifically
      inhibit the induction of NF-kappaB activation without inhibiting the basal NF
      kappaB activity. The present study demonstrates the effectiveness of NBD peptides
      in inhibiting the disease process in adoptively transferred experimental allergic
      encephalomyelitis (EAE), an animal model of multiple sclerosis. Clinical symptoms
      of EAE were much lower in mice receiving wild-type (wt)NBD peptides compared with
      those receiving mutated (m)NBD peptides. Histological and immunocytochemical
      analysis showed that wtNBD peptides inhibited EAE-induced spinal cord mononuclear
      cell invasion and normalized p65 (the RelA subunit of NF-kappaB) expression
      within the spinal cord. Analysis of lymph node cells isolated from donor and
      recipient mice showed that wtNBD peptides but not mNBD peptides were able to
      shift the immune response from a Th1 to a Th2 profile. Consistently, wtNBD
      peptides but not mNBD peptides inhibited the encephalitogenicity of myelin basic
      protein-specific T cells. Furthermore, i.p. injection of wtNBD peptides but not
      mNBD peptides was also able to reduce LPS- and IFN-gamma-induced expression of
      inducible NO synthase, IL-1beta, and TNF-alpha in vivo in the cerebellum. Taken
      together, our results support the conclusion that NBD peptides are
      antineuroinflammatory, and that NBD peptides may have therapeutic effect in
      neuroinflammatory disorders such as multiple sclerosis.

PMID- 15240730
TI  - Regulatory role of C5a on macrophage migration inhibitory factor release from
      neutrophils.
AB  - There is evidence that C5a and macrophage migration inhibitory factor (MIF) both
      play important roles in experimental sepsis. Humans with sepsis also show
      elevated levels of both mediators in the blood. Regulation of MIF during sepsis
      is poorly understood. We now demonstrate that neutrophil depletion greatly
      reduced serum MIF levels in rats and mice during the onset of sepsis after cecal
      ligation and puncture. In vitro, C5a induced MIF release from rat and mouse
      neutrophils. In vivo blockade of C5aR or absence of C5aR led to significantly
      reduced MIF generation during the onset of sepsis. C5a-induced release in vitro
      of MIF from neutrophils appeared to be due to up-regulation of MIF in cytoplasmic
      granules of neutrophils via activation of the protein kinase B signaling pathway
      together with involvement of PI3K. Our data suggest that C5a plays a role in
      enhancing MIF release from neutrophils in vitro and during sepsis. These findings
      represent a previously unrecognized function of C5a and neutrophils in the
      appearance of MIF in sepsis.

PMID- 15240731
TI  - Blockade of allergic airway inflammation following systemic treatment with a B7
      dendritic cell (PD-L2) cross-linking human antibody.
AB  - We present a novel immunotherapeutic strategy using a human B7-DC cross-linking
      Ab that prevents lung inflammation, airway obstruction, and hyperreactivity to
      allergen in a mouse model of allergic inflammatory airway disease. Dendritic
      cells (DC) have the ability to skew the immune response toward a Th1 or Th2
      polarity. The sHIgM12 Ab functions in vitro by cross-linking the costimulatory
      family molecule B7-DC (PD-L2) on DC up-regulating IL-12 production, homing to
      lymph nodes, and T cell-activating potential of these APCs. Using chicken OVA as
      a model Ag, the administration of sHIgM12 Ab to BALB/c mice blocked lung
      inflammation, airway pathology, and responsiveness to methacholine, even after
      animals were presensitized and a Th2-polarized immune response was established.
      This therapeutic strategy was ineffective in STAT4-deficient animals, indicating
      that IL-12 production is critical in this system. Moreover, the polarity of the
      immune response upon in vitro restimulation with Ag is changed in wild-type mice,
      with a resulting decrease in Th2 cytokines IL-4 and IL-5 and an increase in the
      immunoregulatory cytokine IL-10. These studies demonstrate that the immune
      response of hypersensitized responders can be modulated using B7-DC cross-linking
      Abs, preventing allergic airway disease upon re-exposure to allergen.

PMID- 15240732
TI  - An advanced intercross line resolves Eae18 into two narrow quantitative trait
      loci syntenic to multiple sclerosis candidate loci.
AB  - Identification of polymorphic genes regulating inflammatory diseases may unravel
      crucial pathogenic mechanisms. Initial steps to map such genes using linkage
      analysis in F(2) intercross or backcross populations, however, result in broad
      quantitative trait loci (QTLs) containing hundreds of genes. In this study, an
      advanced intercross line in combination with congenic strains, was used to fine
      map Eae18 on rat chromosome 10 in myelin oligodendrocyte glycoprotein-induced
      experimental autoimmune encephalomyelitis (EAE). Myelin oligodendrocyte
      glycoprotein-induced EAE is a chronic relapsing disease that closely mimics key
      features of multiple sclerosis. Congenic DA.ACI rat strains localized Eae18 to an
      approximately 30-Mb large region. Fine-mapping was then performed in an advanced
      intercross line consisting of a (DA x PVG.1AV1)F(7) intercross, resulting in two
      adjacent EAE-regulating QTLs designated Eae18a and Eae18b. The two QTLs span 5.5
      and 3 Mb, respectively, and the 3-Mb Eae18b contains as few as 10 genes,
      including a cluster of chemokine genes (CCL1, CCL2, CCL7, and CCL11). Eae18a and
      Eae18b are syntenic to human chromosome 17p13 and 17q11, respectively, which both
      display linkage to multiple sclerosis. Thus, Eae18 consists of at least two EAE
      regulating genes, providing additional evidence that clustering of disease
      regulating genes in QTLs is an important phenomenon. The overlap between Eae18a
      and Eae18b with previously identified QTLs in humans and mice further supports
      the notion that susceptibility alleles in inflammatory disease are evolutionary
      conserved between species.

PMID- 15240733
TI  - Activated Ets2 is required for persistent inflammatory responses in the motheaten
      viable model.
AB  - The Ets2 transcription factor is constitutively phosphorylated on residue Thr(72)
      in macrophages derived from mice homozygous for the motheaten viable (me-v)
      allele of the hemopoietic cell phosphatase (Hcph) gene. To genetically test the
      importance of signaling through residue Thr(72) of Ets2 during inflammation, the
      Ets2(A72) mutant allele, which cannot be phosphorylated on Thr(72), was combined
      with the Hcph(me-v) allele in mice. Ets2(A72/A72) moderated the inflammation
      related pathology of Hcph(me-v/me-v) mice, as demonstrated by the increased life
      span and the decreased macrophage infiltration in skin and lungs of these mice.
      Macrophage apoptosis induced by cytokine withdrawal was also increased in the
      double-mutant mice. Importantly, the Ets2(A72/A72) allele resulted in decreased
      expression of inflammatory response genes, including TNF-alpha, CCL3, matrix
      metalloprotease 9, integrin alpha(M), and Bcl-X in alveolar macrophage. Ets2
      phosphorylation was required for persistent activation of TNF-alpha following LPS
      stimulation of bone marrow-derived macrophages. The phosphorylation of Ets2
      functions in the severe inflammatory phenotype of the me-v model by mediating
      both macrophage survival and inflammatory gene expression.

PMID- 15240734
TI  - A3 adenosine receptor signaling contributes to airway inflammation and mucus
      production in adenosine deaminase-deficient mice.
AB  - Adenosine signaling has been implicated in chronic lung diseases such as asthma
      and chronic obstructive pulmonary disease; however, the specific roles of the
      various adenosine receptors in processes central to these disorders are not well
      understood. In this study, we have investigated the role(s) of the A(3) adenosine
      receptor in adenosine-dependent pulmonary inflammation observed in adenosine
      deaminase (ADA)-deficient mice. The A(3) receptor (A(3)R) was found to be
      expressed in eosinophils and mucus-producing cells in the airways of ADA
      deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A(3)R
      antagonist, prevented airway eosinophilia and mucus production. Similar findings
      were seen in the lungs of ADA/A(3) double knockout mice. Although eosinophils
      were decreased in the airways of ADA-deficient mice following antagonism or
      removal of the A(3)R, elevations in circulating and lung interstitial eosinophils
      persisted, suggesting signaling through the A(3)R is needed for the migration of
      eosinophils into the airways. These findings identify an important role for the
      A(3)R in regulating lung eosinophilia and mucus production in an environment of
      elevated adenosine.

PMID- 15240735
TI  - Mucosal T cells bearing TCRgammadelta play a protective role in intestinal
      inflammation.
AB  - Intestinal intraepithelial lymphocytes (IEL) bearing TCRgammadelta represent a
      major T cell population in the murine intestine. However, the role of gammadelta
      IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we
      show that gammadelta IEL is an important protective T cell population against
      IBD. gammadelta T cell-deficient (Cdelta(-/-)) mice developed spontaneous colitis
      with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene
      sulfonic acid (TNBS)-induced colitis at a young age. Transfer of gammadelta IEL
      to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with
      decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta
      production by IEL. Furthermore, a high level of IL-15, which inhibits activation
      induced cell death to terminate inflammation, was expressed more in intestinal
      epithelial cells (EC) from TNBS-treated Cdelta(-/-) mice than in those from wild
      type mice. EC from wild-type mice significantly suppressed the IFN-gamma
      production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS
      treated Cdelta(-/-) mice did not. These data indicate that gammadelta IEL play
      important roles in controlling IBD by regulating mucosal T cell activation
      cooperated with EC function. Our study suggests that enhancement of regulatory
      gammadelta T cell activity is a possible new cell therapy for colitis.

PMID- 15240736
TI  - Blockade of late stages of autoimmune diabetes by inhibition of the receptor for
      advanced glycation end products.
AB  - Ligation of the receptor for advanced glycation end products (RAGE) occurs during
      inflammation. Engagement of RAGE results in enhanced expression of addressins and
      it is therefore, not surprising that previous studies have shown a role of
      RAGE/ligand interactions in immune responses including cell/cell contact but the
      role of RAGE in spontaneous autoimmunity has not been clearly defined. To study
      the role of RAGE/ligand interactions in autoimmune diabetes, we tested the
      ability of soluble RAGE, a scavenger of RAGE ligands, in late stages of diabetes
      development in the NOD mouse-disease transferred with diabetogenic T cells and
      recurrent disease in NOD/scid recipients of syngeneic islet transplants. RAGE
      expression was detected on CD4(+), CD8(+), and B cells from diabetic mice and
      transferred to NOD/scid recipients. RAGE and its ligand, S100B, were found in the
      islets of NOD/scid mice that developed diabetes. Treatment of recipient NOD/scid
      mice with soluble RAGE prevented transfer of diabetes and delayed recurrent
      disease in syngeneic islet transplants. RAGE blockade was associated with
      increased expression of IL-10 and TGF-beta in the islets from protected mice.
      RAGE blockade reduced the transfer of disease with enriched T cells, but had no
      effect when diabetes was transferred with the activated CD4(+) T cell clone,
      BDC2.5. We conclude that RAGE/ligand interactions are involved in the
      differentiation of T cells to a mature pathogenic phenotype during the late
      stages of the development of diabetes.

PMID- 15240737
TI  - Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori
      associated gastritis.
AB  - TLR4, a member of pattern recognition receptors, is the main receptor of LPS. MD
      2 physically associates with TLR4 on the cell surface and confers LPS
      responsiveness. Helicobacter pylori LPS is one of the major virulence factors for
      induction of gastritis. We demonstrated in this study the role of MD-2 in TLR4
      dependent signaling in H. pylori-associated gastritis. Gastric biopsy samples
      collected from patients with and without H. pylori infection and four gastric
      cancer cell lines were used for this study. TLR-4 and MD-2 expression in biopsy
      specimens and the cell lines was examined by using RT-PCR. Localization of TLR-4
      in histological sections was evaluated by immunohistochemistry. For in vitro
      functional assays, we established stable transfectants of AGS cells expressing
      TLR4 and MD-2. Cellular distribution of TLR4 was examined by flow cytometry. NF
      kappaB activation and activation of IL-8 and MD-2 promoters were assessed by
      reporter gene assay. H. pylori infection up-regulated the TLR4 and MD-2
      expression in gastric mucosa. TLR4 staining was observed predominantly in
      epithelial cells, located in both the cytoplasm and at the apical surface. MD-2
      transfection in AGS cells markedly increased cell surface expression of TLR4 and
      augmented the activation of NF-kappaB and IL-8 promoter upon stimulation with H.
      pylori LPS. Live H. pylori also stimulated transcriptional activation of MD-2.
      This study revealed that MD-2 expression is elevated in gastric epithelial cells
      during H. pylori infection, suggesting that the TLR4/MD-2 system is a potent
      receptor complex involved in the response to H. pylori LPS in the stomach.

PMID- 15240738
TI  - Production of profibrotic cytokines by invariant NKT cells characterizes
      cirrhosis progression in chronic viral hepatitis.
AB  - Invariant (inv)NKT cells are a subset of autoreactive lymphocytes that recognize
      endogenous lipid ligands presented by CD1d, and are suspected to regulate the
      host response to cell stress and tissue damage via the prompt production of
      cytokines. We investigated invNKT cell response during the progression of chronic
      viral hepatitis caused by hepatitis B or C virus infection, a major human disease
      characterized by a diffused hepatic necroinflammation with scarring fibrotic
      reaction, which can progress toward cirrhosis and cancer. Ex vivo frequency and
      cytokine production were determined in circulating and intrahepatic invNKT cells
      from controls (healthy subjects or patients with nonviral benign or malignant
      focal liver damage and minimal inflammatory response) or chronic viral hepatitis
      patients without cirrhosis, with cirrhosis, or with cirrhosis and hepatocellular
      carcinoma. invNKT cells increase in chronically infected livers and undergo a
      substantial modification in their effector functions, consisting in the
      production of the type 2 profibrotic IL-4 and IL-13 cytokines, which
      characterizes the progression of hepatic fibrosis to cirrhosis. CD1d, nearly
      undetectable in noncirrhotic and control livers, is strongly expressed by APCs in
      cirrhotic ones. Furthermore, in vitro CD1d-dependent activation of invNKT cells
      from healthy donors elicits IL-4 and IL-13. Together, these findings show that
      invNKT cells respond to the progressive liver damage caused by chronic hepatitis
      virus infection, and suggest that these cells, possibly triggered by the
      recognition of CD1d associated with viral- or stress-induced lipid ligands,
      contribute to the pathogenesis of cirrhosis by expressing a set of cytokines
      involved in the progression of fibrosis.

PMID- 15240739
TI  - The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses
      the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted
      epitope(s) for multiple sclerosis-associated HLA-DRB1*1501.
AB  - Autoimmune response to the myelin-associated oligodendrocytic basic protein
      (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role
      in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune
      response to MOBP and the associated pathology in the CNS have not yet been fully
      investigated. In this study, we have characterized the clinical manifestations,
      pathology, T cell epitope-specificity, and TCRs associated with experimental
      autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse
      MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells
      for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major
      immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major
      encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical
      EAE associated with intense perivascular and parenchymal infiltrations,
      widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular
      modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of
      the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28
      as the core sequence for I-A(s)-restricted recognition of the encephalitogenic
      region MOBP15-36. Although highly focused in their epitope specificity, the
      encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta
      genes. These results would therefore favor epitope-directed, rather than TCR
      targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity.
      Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP
      epitope within the encephalitogenic MOBP15-36 sequence suggests the potential
      relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15
      36 detected in MS shown here and in another study further emphasizes the
      potential significance of this epitope for MS.

PMID- 15240740
TI  - Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor
      substitute.
AB  - To investigate the effects of anchor substitutions in SYT-SSX junction peptide,
      an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was
      substituted to more favorable residues according to the HLA-A24-binding motif.
      Among four substitutes constructed, a substitute with isoleucine (termed K9I
      peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent
      in vitro CTL induction analysis using PBMCs of 15 HLA-A24(+) synovial sarcoma
      patients revealed that the original B peptide allowed to induce synovial sarcoma
      specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12
      patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA
      A24(+) synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B
      peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction
      was evaluated by cytotoxicity assays against autologous cells and tetramer
      analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not
      lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of
      PBMCs from 5 HLA-A24(+) synovial sarcoma patients with K9I peptide increased the
      frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA
      A24/B peptide tetramer. In contrast, the frequency of T cells reacting with
      HLA/HIV-derived peptide tetramer remained low. These findings support the
      validity in design of anchor residue substitution in SYT-SSX fusion gene-derived
      peptide, and provide a potential clue to the current stagnation in vaccination
      trials of fusion gene-derived natural junction peptides.

PMID- 15240741
TI  - Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human
      metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells.
AB  - Dominant tolerance is mediated by regulatory T cells (T(reg)) that control
      harmful autoimmune T cells in the periphery. In this study, we investigate the
      implication of T(reg) in modulating infiltrating T lymphocytes in human
      metastatic melanoma. We found that CD4(+)CD25(high) T cells are overrepresented
      in metastatic lymph nodes (LNs) with a 2-fold increased frequency compared with
      both tumor-free LNs and autologous PBMCs. These cells express the Foxp3
      transcription factor, display an activated phenotype, and display a polyclonal
      TCR Vbeta chain repertoire. They inhibit in vitro the proliferation and cytokine
      production of infiltrating CD4(+)CD25(-) and CD8(+) T cells (IL-2, IFN-gamma)
      through a cell-contact-dependent mechanism, thus behaving as T(reg). In some
      cases, the presence of T(reg) type 1/Th3-like lymphocytes could also be
      demonstrated. Thus, T(reg) are a major component of the immunosuppressive
      microenvironment of metastatic melanoma LNs. This could explain the poor clinical
      response of cancer patients under immunotherapeutic protocols, and provides a new
      basis for future immunotherapeutic strategies counteracting in vivo T(reg) to
      reinforce local antitumor immune responses.

PMID- 15240742
TI  - Peritoneal exudate cells treated with calcitonin gene-related peptide suppress
      murine experimental autoimmune uveoretinitis via IL-10.
AB  - Immunization with retinal Ag induces experimental autoimmune uveoretinitis (EAU)
      in mice. We investigated the suppression of murine EAU by peritoneal exudate
      cells (PEC) cultured with calcitonin gene-related peptide (CGRP). PEC derived
      from mice were treated with CGRP and residues 1-20 of human interphotoreceptor
      retinoid-binding protein (hIRBP 1-20). The hIRBP 1-20-immunized mice were
      injected i.v. with PEC treated with CGRP and hIRBP 1-20. After immunization, Ag
      specific delayed hypersensitivity (DH) was measured and EAU was assessed
      histopathologically. Both EAU- and Ag-specific DH were suppressed by injection of
      PEC treated with CGRP (100 ng/ml) and hIRBP 1-20. However, hIRBP 1-20-mediated
      EAU was not suppressed by injection of PEC treated with CGRP and BSA. Both EAU-
      and Ag-specific DH were not suppressed by injection of PEC treated with CGRP and
      hIRBP 1-20 into splenectomized mice. In mice adoptively transferred spleen cells
      from hIRBP 1-20-immunized mice, EAU was also suppressed by injection of CGRP
      treated PEC. EAU was markedly inhibited in hIRBP 1-20-immunized mice adoptively
      transferred T cells obtained from mice injected with hIRBP 1-20-pulsed, CGRP
      treated PEC. Furthermore, EAU- and Ag-specific DH were not suppressed by
      injection of PEC treated with CGRP and hIRBP 1-20 when the recipient mice were
      given anti-IL-10 Ab i.p., or when the PEC were derived from IL-10 knockout mice.
      The present results indicate that PEC treated with CGRP suppress murine EAU in an
      Ag-specific manner, even in the efferent phase, and IL-10 secreted from PEC might
      play an important role in the CGRP-mediated suppression of murine EAU.

PMID- 15240743
TI  - IL-15 and the initiation of cell contact-dependent synovial fibroblast-T
      lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate.
AB  - To characterize the molecules responsible for synovial fibroblast-T lymphocyte
      (TL) cross-talk in rheumatoid arthritis (RA), synovial fibroblasts from patients
      with established RA (RASFibs) were cocultured with TLs from peripheral blood of
      early RA patients (RAPBTL). TLs from peripheral blood of healthy controls and
      from synovial fluid of RA served as controls. Adhesion molecules and cytokines
      were determined by flow cytometry, ELISA, and real-time PCR. RAPBTL (n = 20)
      induced an up-regulation of ICAM-1, intracellular IL-8, IL-6, IL-15, and surface
      IL-15 in cocultured RASFibs. In turn, RAPBTL showed an up-regulation of TNF
      alpha, IFN-gamma, IL-17, CD25, and CD69 expression. Responses seen with TLs from
      peripheral blood of healthy controls (n = 20) were significantly lower, whereas
      responses with TLs from synovial fluid of RA (n = 20) were maximal. Blocking Abs
      to IL-15 and CD54, but not an isotype-control Ab, down-regulated the increased TL
      cytokine and activation marker expression. Abs to CD69, CD11a, IL-17, TNF-alpha,
      and IFN-gamma significantly decreased the up-regulation of RASFib cytokine and
      CD54 expression. Cocultures using 0.4- micro m inserts did not result in up
      regulation of surface molecules or cytokines. Methotrexate significantly
      inhibited RASFib/TL cross-talk signals and decreased adhesion of TL to RASFibs.
      In summary, RASFib production of IL-15 induces the proinflammatory cytokines TNF
      alpha, IFN-gamma, and IL-17 in cocultured TLs through a cell contact-dependent
      mechanism. In turn, these cytokines stimulate the expression of IL-15, IL-8, and
      IL-6 in RASFibs, thereby creating a feedback loop that favors persistent synovial
      inflammation. Methotrexate seems to disrupt this loop by decreasing cell
      adhesion.

PMID- 15240744
TI  - Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent, TLR2
      and TLR4-independent induction of IL-18 release.
AB  - Recent studies suggest that inflammation plays a central role in the pathogenesis
      of atherosclerosis, and IFN-gamma is a prominent proinflammatory mediator in this
      context. However, it is unclear what stimuli are responsible for initial
      stimulation of IFN-gamma synthesis in the vessel wall. In the present study, we
      demonstrate that Chlamydia pneumoniae is an important stimulus for IFN-gamma
      synthesis, and this production depends on release of endogenous IL-18, IL-12, and
      IL-1, but not of TNF. The production of the proinflammatory cytokines TNF and IL
      1beta from PBMC by sonicated C. pneumoniae was mediated through TLR2-dependent
      pathways. In contrast, C. pneumoniae stimulated the production of IL-18 through
      MyD88-dependent, TLR2-, TLR4-, and CD14-independent pathways, mediated by
      posttranscriptional mechanisms not involving de novo protein synthesis. In
      conclusion, C. pneumoniae is a potent stimulus of IFN-gamma production, in
      addition to the proinflammatory cytokines TNF and IL-1beta, which may contribute
      to its proatherogenic effects. Most interestingly, C. pneumoniae is also a potent
      inducer of IL-18 production through pathways independent of TLR2 and TLR4.

PMID- 15240745
TI  - Urokinase-deficient and urokinase receptor-deficient mice have impaired
      neutrophil antimicrobial activation in vitro.
AB  - Leukocytes express both urokinase-type plasminogen activator (uPA) and the
      urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the
      lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice
      but is normal in uPA-/- mice. However, both uPA-/- mice and uPAR-/- mice have
      impaired lung clearance of P. aeruginosa compared with wild-type (WT) mice. To
      determine the role of uPA and uPAR in antibacterial host defense, we compared
      neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA
      /-, uPAR-/-, and WT mice. Neutrophil phagocytosis was significantly diminished
      comparing uPA-/- and uPAR-/- mice with WT mice at all time points. The generation
      of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen
      in WT neutrophils. Degranulation of azurophilic granules was significantly
      diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils.
      By contrast, agonist-stimulated release of specific granules was not diminished
      in either uPA-/- or uPAR-/- mice compared with WT. We conclude that the uPA/uPAR
      system modulates several of the crucial steps in neutrophil activation that
      result in bacterial killing and effective innate host defense.

PMID- 15240746
TI  - Changes to peptide structure, not concentration, contribute to expansion of the
      lowest avidity cytotoxic T lymphocytes.
AB  - The efficient in vitro expansion of antigen-specific CD8+ cytotoxic T lymphocytes
      (CTL) for use in adoptive immunotherapy represents an important clinical goal.
      Furthermore, the avidity of expanded CTL populations often correlates closely
      with clinical outcome. In our study, high-avidity CTL lines could be expanded ex
      vivo from an antigen-primed animal using low peptide concentration, and
      intermediate peptide concentrations favored the generation of lower avidity CTL.
      Further increases in peptide concentration during culture inhibited the expansion
      of all peptide-specific CD8+ cells. In contrast, a single amino acid variant
      peptide efficiently generated functional CTL populations at high or low peptide
      concentration, which responded to wild-type epitope with the lowest average
      avidity seen in this study. We propose that for some peptides, the efficient
      generation of low-avidity CTL responses will be favored by stimulation with
      altered peptide rather than high concentrations of wild-type epitope. In
      addition, some variant peptides designed to have improved binding to major
      histocompatibility complex class I may reduce rather than enhance the functional
      avidity for the wild-type peptide of ex vivo-expanded CTL. These observations are
      relevant to in vitro expansion of CTL for immunotherapy and strategies to elicit
      regulatory or therapeutic immunity to neo-self-antigen when central tolerance has
      eliminated high-avidity, cognate T cells.

PMID- 15240747
TI  - Involvement of multiple P2Y receptors and signaling pathways in the action of
      adenine nucleotides diphosphates on human monocyte-derived dendritic cells.
AB  - Adenosine 5'-triphosphate (ATP), which is released from necrotic cells, induces a
      semimaturation state of dendritic cells (DC), characterized by the up-regulation
      of costimulatory molecules and the inhibition of proinflammatory cytokines. This
      action is mediated by cyclic adenosine monophosphate (cAMP) and involves the
      P2Y11 receptor. As DC express the ecto-enzyme CD39, which converts ATP into
      adenosine 5'-diphosphate (ADP), the effects of adenine nucleotides diphosphates
      on molecular signaling [intracellular calcium ([Ca2+]i), cAMP, extracellular
      signal-regulated kinase 1 (ERK1)], costimulatory molecule expression (CD83), and
      cytokine production [interleukin (IL)-12, tumor necrosis factor alpha (TNF
      alpha), IL-10] were investigated in human monocyte-derived DC. ADP, 2-methylthio
      ADP, and ADPbetaS had no effect on cAMP, increased [Ca2+]i, and stimulated the
      phosphorylation of ERK1. The effect on ERK1 was inhibited by AR-C69931MX, a P2Y12
      and P2Y13 antagonist. On the contrary the effect on [Ca2+]i was neither inhibited
      by AR-C69931MX or by the P2Y1 antagonist MRS-2179. Both effects were inhibited by
      pertussis toxin. ADPbetaS alone was less potent for up-regulation of CD83 than
      ATPgammaS and did not increase the CD83 expression by DC stimulated with
      lipopolysaccharide (LPS). Similar to ATPgammaS, ADPbetaS inhibited the release of
      IL-12p40, IL-12p70, and TNF-alpha stimulated by LPS (1-100 ng/ml). The inhibitory
      effect of ADPbetaS on IL-12 release was neither reversed by AR-C69931MX or by MRS
      2179. The two nucleotides had opposite effects on IL-10 production: inhibition by
      ADPbetaS and potentiation by ATPgammaS. In conclusion, ATP can modulate the
      function of DC, directly via a cAMP increase mediated by the P2Y11 receptor and
      indirectly via its degradation into ADP, which acts via Gi-coupled receptors
      coupled to ERK activation and calcium mobilization. These distinct mechanisms
      converge on the inhibition of inflammatory cytokine production, particularly IL
      12, but have a differential effect on IL-10.

PMID- 15240748
TI  - Heme oxygenase 1 expression induced by IL-10 requires STAT-3 and phosphoinositol
      3 kinase and is inhibited by lipopolysaccharide.
AB  - Heme-oxygenase 1 (HO-1) is a stress-response protein with anti-inflammatory
      activity. This study has examined the regulation of HO-1 expression by the anti
      inflammatory factor, interleukin (IL)-10 and whether HO-1 could account for the
      function of the cytokine. IL-10-induced expression of HO-1 required the
      activation of signal transducer and activator of transcription (STAT)-3 but not
      p38 mitogen-activated protein kinase. However, expression of HO-1 also required
      the activation of the phosphatidylinositol-3 kinase pathway, a signaling
      mechanism not required for the anti-inflammatory activity of IL-10. Moreover,
      induction of HO-1 expression was not restricted to IL-10, as IL-6, a cytokine
      known to activate STAT-3, could also induce the protein. In human macrophages,
      lipopolysaccharide inhibited HO-1 expression induced by IL-10. Also, inhibition
      of HO-1 activity by the specific inhibitor zinc-II-protoporphyrin-IX had no
      effect on the anti-inflammatory function of IL-10. In summary, although IL-10
      does regulate HO-1 expression, it does not appear to play a significant role in
      the anti-inflammatory activity of the cytokine.

PMID- 15240749
TI  - Direct quantification of the modulation of interaction between cell- or surface
      bound LFA-1 and ICAM-1.
AB  - The functional activity of leukocyte integrins is highly regulated by several
      mechanisms related to intrinsic molecular properties and receptor interaction
      with the cell membrane. Here, we present a microkinetic study of the lymphocyte
      function-associated antigen-1-mediated interaction between flowing Jurkat cells
      and surface- or cell-bound intercellular adhesion molecule-1 (ICAM-1). We
      conclude that adhesion is initiated by the formation of a single bond with
      approximately 0.3 s(-1) dissociation rate, and attachment is subsequently
      strengthened by the formation of additional bonds during the next 10 s; exposing
      cells to Mg2+ or Mn2+ resulted in up to a 16-fold increase of the binding
      frequency, in line with reported measurements performed on isolated molecules
      with surface plasmon resonance methodology; cell-bound ICAM-1 molecules were more
      efficient in mediating adhesion than Fc-ICAM-1, properly oriented and bound by
      surface-adsorbed protein A; and quantitative analysis of binding frequency
      suggested that adhesion efficiency was ten- to 100-fold lower than the maximum
      value allowed by previously determined association rates of soluble molecules. It
      is concluded that the presented methodology provides a simple and unique way of
      dissecting the initial step of cell adhesion and discriminating between affinity
      and avidity modulation of adhesion receptors.

PMID- 15240750
TI  - The absence of Grb2-associated binder 2 (Gab2) does not disrupt NK cell
      development and functions.
AB  - Scaffolding molecules bind simultaneously and link together various components of
      signal-transduction pathways. Grb2-associated binder 2 (Gab2) is a scaffolding
      protein required for FcgammaR-initiated allergic responses in mast cells and
      FcgammaR-mediated phagocytosis in macrophages, where it links IgE and IgG
      receptors to the phosphatidylinositol-3 kinase (PI-3K) pathway. The FcgammaR
      expressed by natural killer (NK) cells triggers antibody-dependent cellular
      cytotoxicity (ADCC). We show here that mouse NK cells express Gab2 and that
      although PI-3K was required for ADCC, this FcgammaR-mediated function was normal
      in Gab2-/- NK cells. Moreover, NK cell development, spontaneous cytotoxicity, and
      responses to and production of cytokines were not perturbed in Gab2-/- mice.
      Considering the striking differences between the signaling requirements of
      FcgammaR in macrophages and NK cells, our findings suggest that the organization
      of signal transduction downstream of the same FcR can be cell type-specific.
      Conversely, Gab family members Gab1, Gab2, and Gab3 may play specific roles in
      different leukocytes. As pharmacological targeting of Gab2 in mast cells is a
      potential strategy to treat allergy, our results suggest prudence, as NK cells
      may participate in IgE-mediated anaphylaxis in a Gab2-independent manner.

PMID- 15240751
TI  - Human milk oligosaccharides reduce platelet-neutrophil complex formation leading
      to a decrease in neutrophil beta 2 integrin expression.
AB  - Human milk is thought by many authorities to be preferable to formula as a source
      of nutrients for infants. Some of the benefits may stem from its high
      concentration of unbound oligosaccharides (5-10 g/L). These sugars have
      structural similarities to selectin ligands, known to mediate important cell-cell
      interactions in the immune system. Platelet-neutrophil complexes (PNC) exist in
      healthy individuals but have been implicated in disease states. Formation of
      these complexes requires selectins and as such, could be influenced by human milk
      oligosaccharides (HMO). Here, we investigate this possibility by examining the
      effect of HMO on the formation of PNC and activation of associated neutrophils.
      We collected blood from 10 healthy volunteers, activated platelets with adenosine
      5'-diphosphate, and added HMO, oligosaccharide standards, or phosphate-buffered
      saline as a control. We determined the influence of HMO on PNC formation and
      adjacent neutrophil activation with fluorescein-activated cell sorter analysis
      after labeling with antibodies for the platelet marker CD42a and the neutrophil
      activation marker CD11b. Within physiologically achievable concentrations (6.25
      125 microg/mL), an acidic HMO fraction reduced PNC formation up to 20%, which was
      similar to the effect seen with high concentrations of sialyl-Lewis x. Associated
      neutrophils showed a dose-dependent decrease in beta 2 integrin expression, up to
      30%, at high but physiological concentrations. The neutral HMO fraction had no
      effect. These results support the hypothesis that acidic HMO serve as anti
      inflammatory components of human milk and thus, contribute to the lower incidence
      of inflammatory diseases such as necrotizing enterocolitis in breast-fed versus
      formula-fed infants.

PMID- 15240752
TI  - Structure and regulation of the neutrophil respiratory burst oxidase: comparison
      with nonphagocyte oxidases.
AB  - Neutrophils play an essential role in the body's innate defense against pathogens
      and are one of the primary mediators of the inflammatory response. To defend the
      host, neutrophils use a wide range of microbicidal products, such as oxidants,
      microbicidal peptides, and lytic enzymes. The generation of microbicidal oxidants
      by neutrophils results from the activation of a multiprotein enzyme complex known
      as the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which
      is responsible for transferring electrons from NADPH to O2, resulting in the
      formation of superoxide anion. During oxidase activation, cytosolic oxidase
      proteins translocate to the phagosome or plasma membrane, where they assemble
      around a central membrane-bound component known as flavocytochrome b. This
      process is highly regulated, involving phosphorylation, translocation, and
      multiple conformational changes. Originally, it was thought that the NADPH
      oxidase was restricted to phagocytes and used solely in host defense. However,
      recent studies indicate that similar NADPH oxidase systems are present in a wide
      variety of nonphagocytic cells. Although the nature of these nonphagocyte NADPH
      oxidases is still being defined, it is clear that they are functionally distinct
      from the phagocyte oxidases. It should be noted, however, that structural
      features of many nonphagocyte oxidase proteins do seem to be similar to those of
      their phagocyte counterparts. In this review, key structural and functional
      features of the neutrophil NADPH oxidase and its protein components are
      described, including a consideration of transcriptional and post-translational
      regulatory features. Furthermore, relevant details about structural and
      functional features of various nonphagocyte oxidase proteins will be included for
      comparison.

PMID- 15240753
TI  - Differing caspase-1 activation states in monocyte versus macrophage models of IL
      1beta processing and release.
AB  - The release of IL-1beta as an active, mature cytokine requires proteolytic
      processing by caspase-1, which is recruited to signaling complexes that
      facilitate its autocatalytic proteolysis and activation. Caspase-1 processing has
      been characterized in human monocyte and murine macrophage model systems, and
      comparative analyses indicate significant mechanistic differences in caspase-1
      activation by these cell types. In this study, we used an in vitro processing
      assay to compare caspase-1 activation in THP-1 human monocytes vs. Bac1.2F5
      murine macrophages. These in vitro caspase-1 and IL-1beta processing reactions
      indicated a higher rate of constitutive caspase-1 activation in lysates from THP
      1 vs. Bac1 cells. Transfer of small amounts of THP-1 lysate to Bac1 lysate
      rapidly increased in vitro procaspase-1 and proIL-1beta processing in the latter
      preparation. The transferable activation factor(s) was heat-labile, > or =10 kDa,
      and unaffected by immunodepletion of procaspase-1 from the THP-1 lysate. This
      transactivating effect of THP-1 lysate on processing in Bac1 lysates could be
      mimicked by addition of purified recombinant human caspase-1. The constitutive
      caspase-1 and IL-1beta processing reactions in THP-1 lysates were insensitive to
      pharmacological blockade by the tyrphostin, AG126, and the phospholipase A2
      inhibitor bromoenol lactone (BEL); contrarily, the same processing reactions were
      inhibited in lysates from Bac1 cells pretreated with either AG126 or BEL. These
      observations indicate significant biochemical differences in the assembly and
      regulation of caspase-1 signaling complexes within human monocyte and murine
      macrophage models of inflammatory activation. These differences need to be
      considered when comparing or pharmacologically manipulating IL-1beta processing
      and release in various model systems.

PMID- 15240754
TI  - Development of intestinal inflammation in double IL-10- and leptin-deficient
      mice.
AB  - Leptin-deficient (ob/ob) mice are resistant in different models of autoimmunity
      and inflammation, suggesting that leptin regulates immunity and inflammation. To
      investigate whether leptin deficiency modulates the spontaneous intestinal
      inflammation observed in interleukin (IL)-10-deficient mice, double IL-10- and
      leptin-deficient [IL-10 knockout (KO) ob/ob] mice were generated and compared
      with single IL-10 KO mice for colitis severity. Body weight in IL-10 KO ob/ob
      mice was significantly reduced compared with that of ob/ob mice. However, when
      compared with wild-type or IL-10 KO mice, IL-10 KO ob/ob mice were still markedly
      obese. IL-10 KO and IL-10 KO ob/ob mice developed colitis with a comparable time
      course and severity in terms of macroscopic and histologic scores. Likewise,
      production of interferon-gamma, IL-6, and IL-13 from colon cultures and
      splenocytes did not differ among these two groups. Conversely, rates of apoptosis
      were higher in lamina propria lymphocytes obtained from the colon of IL-10 KO
      ob/ob compared with IL-10 KO mice. In conclusion, although leptin deficiency has
      been associated with resistance in models of autoimmunity and inflammation
      induced by exogenous stimuli, leptin appears not to play a significant role in
      the spontaneous colitis of IL-10 KO mice, although it modulates survival of
      intestinal lymphocytes.

PMID- 15240755
TI  - Dendritic cells derived from BCG-infected precursors induce Th2-like immune
      response.
AB  - Human monocytes can differentiate into dendritic cells (DCs) according to the
      nature of environmental signals. We tested here whether the infection with the
      live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be
      limited in preventing pulmonary tuberculosis, modulates monocyte and DC
      differentiation. We found that monocytes infected with BCG differentiate into
      CD1a- DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating
      factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of
      maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines
      (tumor necrosis factor alpha, IL-1beta, IL-6) and IL-10 but not IL-12. BCG-DCs
      were able to stimulate allogeneic T lymphocytes to a similar degree as DCs
      generated in the absence of infection. However, BCG-DCs induced IL-4 production
      when cocultured with human cord-blood mononuclear cells. The induction of IL-4
      production by DCs generated by BCG-infected monocytes could explain the failure
      of the BCG vaccine to prevent pulmonary tuberculosis.

PMID- 15240756
TI  - Sorting soluble tumor necrosis factor (TNF) receptor for storage and regulated
      secretion in hematopoietic cells.
AB  - Hematopoietic cells contain secretory lysosomes that degranulate at sites of
      inflammation. We envisage that secretory granules can act as vehicles for
      targeting inflammatory sites, including malignancies, and thereafter, locally
      release therapeutically active agents to these sites. Exogenous proteins, such as
      the soluble tumor necrosis factor receptor 1 (sTNFR1), have been shown previously
      to be targeted to secretory lysosomes [1]. In this work, we asked whether
      exogenous, secretory lysosome-targeted proteins were subject to regulated
      secretion. sTNFR1-transmembrane (tm)-cytosol-sorting signal (Y) and sTNFR1-tm-Y
      enhanced green fluorescent protein (egfp) were expressed in rat basophilic
      leukemia cell clones having different secretory capacities. sTNFR1-tm-Y was
      targeted directly from the Golgi to secretory lysosomes, followed by generation
      of membrane-free sTNFR1, whose secretion could be triggered by a Ca2+ ionophore
      or immunoglobulin E receptor activation. In contrast, sTNFR1-tm-Y-egfp was
      targeted to the plasma membrane and then subjected to endocytosis and presumably,
      secretory lysosome targeting, as judged by results from antibody ligation and
      cell-surface biotinylation. Activation of protein kinase C with phorbol ester
      promoted ectodomain shedding at the cell surface, resulting in sTNFR1 release
      from sTNFR1-tm-Y-egfp. These results support a concept for using the storage
      organelles of hematopoietic cells as vehicles for targeting sites of inflammation
      with therapeutically active agents.

PMID- 15240758
TI  - Electrophysiological properties of mouse horizontal cell GABAA receptors.
AB  - GABA-induced currents have been characterized in isolated horizontal cells from
      lower vertebrates but not in mammalian horizontal cells. Therefore horizontal
      cells were isolated after enzymatical and mechanical dissociation of the adult
      mouse retina and visually identified. We recorded from horizontal cell bodies
      using the whole cell and outside-out configuration of the patch-clamp technique.
      Extracellular application of GABA induced inward currents carried by chloride
      ions. GABA-evoked currents were completely and reversibly blocked by the
      competitive GABAA receptor antagonist bicuculline (IC50 = 1.7 microM), indicating
      expression of GABAA but not GABAC receptors. Their affinity for GABA was moderate
      (EC50 = 30 microM), and the Hill coefficient was 1.3, corresponding to two GABA
      binding sites. GABA responses were partially reduced by picrotoxin with
      differential effects on peak and steady-state current values. Zinc blocked the
      GABA response with an IC50 value of 7.3 microM in a noncompetitive manner.
      Furthermore, GABA receptors of horizontal cells were modulated by extracellular
      application of diazepam, zolpidem, methyl 6,7-dimethoxy-4-ethyl-beta-carboxylate,
      pentobarbital, and alphaxalone, thus showing typical pharmacological properties
      of CNS GABAA receptors. GABA-evoked single-channel currents were characterized by
      a main conductance state of 29.8 pS and two subconductance states (20.2 and 10.8
      pS, respectively). Kinetic analysis of single-channel events within bursts
      revealed similar mean open and closed times for the main conductance and the 20.2
      pS subconductance state, resulting in open probabilities of 44.6 and 42.7%,
      respectively. The ratio of open to closed times, however, was significantly
      different for the 10.8-pS subconductance state with an open probability of 57.2%.

PMID- 15240757
TI  - Chemokine expression during the development and resolution of a pulmonary
      leukocyte response to influenza A virus infection in mice.
AB  - Influenza A virus replicates in the respiratory epithelium and induces an
      inflammatory infiltrate comprised of mononuclear cells and neutrophils. To
      understand the development of the cell-mediated immune response to influenza and
      how leukocyte trafficking to sites of inflammation is regulated, we examined the
      chemokine expression pattern in lung tissue from A/PR/8/34-infected C57BL/6 mice
      using an RNase protection assay. Monocyte chemoattractant protein 1, macrophage
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-3alpha, regulated on
      activation, normal T expressed and secreted (RANTES), MIP-2, and interferon
      inducible protein 10 (IP-10) mRNA expression was up-regulated between days 5 and
      15 after infection, consistent with a role for these chemokines in leukocyte
      recruitment to the lung. Low levels of expression were detected for the CC
      chemokine receptors (CCR)2 and CCR5, whereas CXC chemokine receptor (CXCR)3 was
      significantly up-regulated by day 10 after infection, coinciding with peak
      inflammatory cell infiltration in the airways. As RANTES, IP-10, and their
      receptors were up-regulated during influenza virus infection, we investigated
      leukocyte recruitment and viral clearance in mice deficient in RANTES or CXCR3,
      the receptor for IP-10. Leukocyte recruitment and viral replication in influenza
      infected RANTES knockout(-/-) mice were similar to that in control mice, showing
      that RANTES is not essential for the immune response to influenza infection.
      Similarly, leukocyte recruitment and viral replication in CXCR3-/- mice were
      identical to control mice, except at day 8 postinfection, where fewer
      lymphocytes, neutrophils, and eosinophils were detected in the bronchoalveolar
      lavage of CXCR3-/- mice. These studies suggest that although the chemokines
      detected may play a role in regulating leukocyte trafficking to the lung during
      influenza infection, some may be functionally redundant.

PMID- 15240759
TI  - Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic
      currents in a mouse model of Huntington disease.
AB  - Huntington disease (HD) is an inherited neurodegenerative disease caused by
      expansion of a polyglutamine tract near the N terminus of the protein huntingtin,
      leading to dramatic loss of striatal medium-sized spiny GABAergic projection
      neurons (MSNs). Evidence suggests overactivation of N-methyl-D-aspartate (NMDA)
      type glutamate receptors (NMDARs) contributes to selective degeneration of MSNs
      in HD. Striatal MSNs are enriched in NR2B, and whole cell current and
      excitotoxicity mediated predominantly by the NR2B subtype of NMDARs is increased
      with expression of mutant huntingtin in transfected cell lines and striatal MSNs
      from mice models. To test whether synaptic NMDAR current is altered by mutant
      huntingtin expression, we recorded striatal MSN excitatory postsynaptic currents
      (EPSCs) evoked by stimulation of cortical afferents in corticostriatal slices
      from YAC72 mice and their wild-type (WT) littermates at age 21-31 days. The ratio
      of NMDAR- to AMPAR-mediated EPSC amplitude was significantly increased in YAC72
      compared to WT mice. Furthermore, using a paired-pulse stimulation protocol as a
      measure of presynaptic glutamate release probability, we found no significant
      differences between YAC72 and WT striatal MSN responses. These data suggest
      selective potentiation of postsynaptic NMDAR activity at corticostriatal synapses
      in YAC72 mice. Measurements of EPSC decay kinetics, as well as the effects of
      NR2B-subtype selective antagonists and glycine concentration on EPSC amplitude,
      are consistent with the majority of postsynaptic NMDARs being triheteromers of
      NR1/NR2A/NR2B in both WT and YAC72 mice. Together with previous results, our data
      suggest that enhanced activity of NR2B-containing NMDARs is one of the earliest
      changes leading to neuronal degeneration in HD.

PMID- 15240760
TI  - Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic
      spiking.
AB  - Long-term depression (LTD) was induced in neocortical layer 5 pyramidal
      connections by pairing presynaptic firing with subthreshold postsynaptic
      depolarization (dLTD) or via a spike-timing protocol (tLTD). Like tLTD, dLTD
      reduced short-term depression and increased the coefficient of variation
      consistent with a presynaptic site of expression. Also like tLTD, dLTD was
      blocked by CB1 cannibinoid receptor blockade and required activation of
      presumably presynaptic NR2B-containing N-methyl-D-aspartate receptors. The two
      forms of LTD had identical magnitudes and time courses and occluded one another,
      and neither depended on frequency. Finally, dLTD shares with tLTD the asymmetric
      temporal window of induction. In conclusion, the types of LTD induced by these
      two protocols are indistinguishable, suggesting that the mechanism that underlies
      tLTD paradoxically does not require postsynaptic spiking: The subthreshold
      postsynaptic depolarizations of dLTD appear to fully substitute for postsynaptic
      spiking.

PMID- 15240761
TI  - High-threshold, Kv3-like potassium currents in magnocellular neurosecretory
      neurons and their role in spike repolarization.
AB  - We identified Kv3-like high-threshold K+ currents in hypothalamic supraoptic
      neurons using whole cell recordings in hypothalamic slices and in acutely
      dissociated neurons. Tetraethylammonium (TEA)-sensitive currents (< 1 mM TEA)
      evoked from -50 mV were characterized by a large component that inactivated in 10
      30 ms, and a smaller, persistent component that inactivated in 1-2 s. I/V
      relations in dissociated neurons revealed TEA-subtracted currents with a slope
      and voltage dependency consistent with the presence of Kv3-like channels. In
      slices, tests with 0.01-0.7 mM TEA produced an IC50 of 200-300 nM for both fast
      and persistent currents. The fast transient current was similar to currents
      associated with the expression of Kv3.4 subunits, given that it was sensitive to
      BDS-I (100 nM). The persistent TEA-sensitive current appeared similar to those
      attributed to Kv3.1/3.2 subunits. Although qualitatively similar, oxytocin (OT)
      and vasopressin (VP) neurons in slices differed in the stronger presence of
      persistent current in VP neurons. In both cell types, the IC50 for TEA-induced
      spike broadening was similar to that observed for current suppression in voltage
      clamp. However, TEA had a greater effect on the spike width of VP neurons than of
      OT neurons. Immunochemical studies revealed a stronger expression of the Kv3.1b
      alpha-subunit in VP neurons, which may be related to the greater importance of
      this current type in VP spike repolarization. Because OT and VP neurons are not
      considered fast firing, but do exhibit frequency- and calcium-dependent spike
      broadening, Kv3-like currents may be important for maintaining spike width and
      calcium influx within acceptable limits during repetitive firing.

PMID- 15240762
TI  - Analysis and simulation of gain control and precision in crayfish visual
      interneurons.
AB  - Impulse trains in sustaining and dimming fibers of crayfish optic lobe (in situ)
      were elicited with sinusoidal extrinsic current and sine-wave illumination.
      Extrinsic currents and currents derived from postsynaptic potentials (PSPs) were
      used to compute the time course of the spike train with an adaptive integrate-and
      fire model. The neurons exhibit variations in gain and spike timing precision
      related to the frequency of stimulation. These phenomena are influenced by spike
      frequency adaptation and nonlinearities in the PSP. Dimming fibers exhibit
      relatively strong spike-frequency adaptation and an associated increase in gain
      with the frequency of sinusoidal extrinsic current and sine-wave illumination.
      The dimming fiber IPSP promotes spike train rectification, and rectification
      contributes to spike timing precision. Sustaining fibers exhibit weaker spike
      frequency adaptation and the gain of the current-elicited response is less
      sensitive to stimulus frequency. The sustaining fiber excitatory PSP, however,
      exhibits a strong frequency-dependent nonlinearity that influences the frequency
      response. Spike timing precision is a function of stimulus frequency in all cells
      and it is enhanced by rectification of the discharge and/or resonance. In
      rectified responses the jitter in spike times is closely related to the variance
      in the times the membrane potential reaches spike threshold. These gain and spike
      timing results are well approximated by the simulated responses. Because the
      nonlinearity of the sustaining fiber PSP entails a high rate of depolarization,
      the PSP can increase the precision of spike timing by 10- to 100-fold compared
      with the response to pure sine-wave stimuli. This enhanced precision has
      implications for crayfish oculomotor reflexes that are driven by sustaining
      fibers and highly sensitive to impulse timing during transient excitation.

PMID- 15240763
TI  - Membrane and firing properties of glutamatergic and GABAergic neurons in the rat
      medial vestibular nucleus.
AB  - In previous studies, neurons in the medial vestibular nucleus (MVN) were
      classified mainly into 2 types according to their intrinsic membrane properties
      in in vitro slice preparations. However, it has not been determined whether the
      classified neurons are excitatory or inhibitory ones. In the present study, to
      clarify the relationship between the chemical and electrophysiological properties
      of MVN neurons, we explored mRNAs of cellular markers for GABAergic (glutamic
      acid decarboxylase 65, 67, and neuronal GABA transporter), glutamatergic
      (vesicular glutamate transporter 1 and 2), glycinergic (glycine transporter 2),
      and cholinergic neurons (choline acetyltransferase and vesicular acetylcholine
      transporter) expressed in electrophysiologically characterized MVN neurons in rat
      brain stem slice preparations. For this purpose, we combined whole cell patch
      clamp recording analysis with single-cell reverse transcription-polymerase chain
      reaction (RT-PCR) analysis. We examined the membrane properties such as
      afterhyperpolarization (AHP), firing pattern, and response to hyperpolarizing
      current pulse to classify MVN neurons. From the single-cell RT-PCR analysis, we
      found that GABAergic neurons consisted of heterogeneous populations with
      different membrane properties. Comparison of the membrane properties of GABAergic
      neurons with those of other neurons revealed that AHPs without slow components
      and a firing pattern with delayed spike generation (late spiking) were
      preferential properties of GABAergic neurons. On the other hand, most
      glutamatergic neurons formed a homogeneous subclass of neurons exhibiting AHPs
      with slow components, repetitive firings with constant interspike intervals
      (continuous spiking), and time-dependent inward rectification in response to
      hyperpolarizing current pulses. We also found a small number of cholinergic
      neurons with various membrane properties. These findings clarify the
      electrophysiological properties of excitatory and inhibitory neurons in the MVN,
      and the information about the preferential membrane properties may be useful for
      identifying GABAergic and glutamatergic MVN neurons electrophysiologically.

PMID- 15240764
TI  - Common input to motor units of digit flexors during multi-digit grasping.
AB  - The control of whole hand grasping relies on complex coordination of multiple
      forces. While many studies have characterized the coordination of finger forces
      and torques, the control of hand muscle activity underlying multi-digit grasping
      has not been studied to the same extent. Motor-unit synchrony across finger
      muscles or muscle compartments might be one of the factors underlying the limited
      individuation of finger forces. Such "unwanted" coupling among finger forces,
      however, might be desirable when a high level of force coupling is required to
      prevent object slip during grasping. The goal of this study was to quantify the
      strength of synchrony between single motor units from extrinsic hand muscles as
      subjects held a device with a five-digit grasp. During the hold phase, we
      recorded the normal force exerted by each digit and the electrical activity of
      single motor units from each of the four divisions of the muscle flexor digitorum
      profundus (FDP) and one thumb flexor muscle, m. flexor pollicis longus (FPL). The
      strength of motor-unit synchrony was quantified by the common input strength
      index (CIS). We found moderate to strong motor-unit synchrony between FPL and the
      index FDP compartment [CIS: 0.49 +/- 0.03 (SE)] and across most FDP compartments
      (0.34 +/- 0.02). Weak synchrony, however, was found between FPL and the middle,
      ring, and little finger FDP compartments (0.25 +/- 0.01). This difference might
      reflect the larger force contribution of the thumb-index finger pair relative to
      other thumb-finger combinations in five-digit grasping.

PMID- 15240765
TI  - Engagement of rat striatal neurons by cortical epileptiform activity investigated
      with paired recordings.
AB  - The striatum is thought to play an important role in the spreading of epilepsy
      from cortical areas to deeper brain structures, but this issue has not been
      addressed with intracellular techniques. Paired recordings were used to assess
      the impact of cortical epileptiform activity on striatal neurons in brain slices.
      Bath-application of 4-amynopyridine (100 microM) and bicuculline (20 microM)
      induced synchronized bursts in all pairs of cortical neurons (< or = 5 mm apart)
      in coronal, sagittal, and oblique slices (which preserve connections from the
      medial agranular cortex to the striatum). Under these conditions, striatal medium
      spiny neurons (MSs) displayed a strong increased spontaneous glutamatergic
      activity. This activity was not correlated to the cortical bursts and was
      asynchronous in pairs of MSs. Sporadic, large-amplitude synchronous
      depolarizations also occurred in MSs. These events were simultaneously detected
      in glial cells, suggesting that they were accompanied by considerable increases
      in extracellular potassium. In oblique slices, cortically driven bursts were also
      observed in MSs. These events were synchronized to cortical epileptiform bursts,
      depended on non-N-methyl-D-aspartate (NMDA) glutamate receptors, and persisted in
      the cortex, but not in the striatum, after disconnection of the two structures.
      During these bursts, MS membrane potential shifted to a depolarized value (59 +/-
      4 mV) on which an irregular waveform, occasionally eliciting spikes, was
      superimposed. Thus synchronous activation of a limited set of corticostriatal
      afferents can powerfully control MSs. Cholinergic interneurons located < 120
      microm from simultaneously recorded MSs, did not display cortically driven
      bursts, suggesting that these cells are much less easily engaged by cortical
      epileptiform activity.

PMID- 15240766
TI  - Voltage-gated calcium channels mediate intracellular calcium increase in weaver
      dopaminergic neurons during stimulation of D2 and GABAB receptors.
AB  - The weaver (wv) mutation affects the pore-forming region of the inwardly
      rectifying potassium channel (GIRK) leading to degeneration of cerebellar granule
      and midbrain dopaminergic neurons. The mutated channel (wvGIRK) loses its
      potassium selectivity, allowing sodium (Na+) and possibly calcium ions (Ca2+) to
      enter the cell. Here we performed whole cell patch-clamp recordings combined with
      microfluorometry to investigate possible differences in calcium ([Ca2+]i)
      dynamics in native dopaminergic neurons (expressing the wvGIRK2 subunits) in the
      midbrain slice preparation from homozygous weaver (wv/wv) and control (+/+) mice.
      Under resting conditions, [Ca2+]i was similar in wv/wv compared with +/+ neurons.
      Activation of wvGIRK2 channels by D2 and GABAB receptors increased [Ca2+]i in
      wv/wv neurons, whereas activation of wild-type channels decreased [Ca2+]i in +/+
      neurons. The calcium rise in wv/wv neurons was abolished by antagonists of the
      voltage-gated calcium channels (VGCC); voltage clamp of the neuron at -60 mV; and
      hyperpolarization of the neuron to -80 mV or more, in current clamp, and was
      unaffected by TTX. Therefore we propose that wvGIRK2 channels in native dopamine
      neurons are not permeable to Ca2+, and when activated by D2 and GABAB receptors
      they mediate membrane depolarization and an indirect Ca2+ influx through VGCC
      rather than via wvGIRK2 channels. Such calcium influx may be the trigger for
      calcium-mediated excitotoxicity, responsible for selective neuronal death in
      weaver mice.

PMID- 15240767
TI  - Comparative morphology of rodent vestibular periphery. I. Saccular and utricular
      maculae.
AB  - Calyx afferents, a group of morphologically and physiologically distinct afferent
      fibers innervating the striolar region of vestibular sensory epithelia, are
      selectively labeled by antibodies to the calcium-binding protein calretinin. In
      this study, the population of calretinin-stained calyx afferents was used to
      delineate and quantify the striolar region in six rodent species: mouse, rat,
      gerbil, guinea pig, chinchilla, and tree squirrel. Morphometric studies and hair
      cell and calyx afferent counts were done. Numbers of hair cells, area, length,
      and width of the sensory epithelium increase from mouse to tree squirrel. In the
      mouse and rat, calretinin is found in 5-9% of all type I hair cells, 20-40% of
      striolar type II hair cells, and 70-80% of extrastriolar type II hair cells.
      Numbers of calyx afferents increase from mouse to squirrel, with more complex
      calyx afferents in larger species. About 10% of calyx afferents are branched.
      Based on our counts of total numbers of calyx afferents in chinchilla maculae and
      in comparison to fiber counts in the literature, the proportion of calyx
      afferents is greater than previously described, constituting nearly 20% of the
      total. Because morphometric measures increase with body weight, we obtained
      additional data on vestibular end organ surface areas from the literature and
      used this to construct a power law function describing this relationship. The
      function holds for species with body weights less than approximately 4 kg.
      Greater than 4 kg, the surface area of the sensory epithelia remains constant
      even with increasing body weight.

PMID- 15240768
TI  - Comparative morphology of rodent vestibular periphery. II. Cristae ampullares.
AB  - We made flattened neuroepithelial preparations of horizontal and vertical
      (anterior and posterior) cristae from mouse, rat, gerbil, guinea pig, chinchilla,
      and tree squirrel. Calretinin immunohistochemistry was used to label the calyx
      class of afferents. Because these afferents are restricted to the central zone of
      the crista, their distribution allowed us to delineate this zone. In addition to
      calyx afferents, calretinin also labels approximately 5% of type I hair cells and
      20% of type II hair cells throughout the mouse and rat crista epithelium.
      Measurements of the dimensions of the cristae and counts of hair cells and calyx
      afferents were determined on all species. Numbers of calyx afferents, hair cells,
      area, length, and width of the sensory epithelium increase from mouse to tree
      squirrel. As in the companion paper, we obtained additional data on vestibular
      end organ dimensions from the literature to construct a power law function
      describing the relationship between crista surface area and body weight. The
      vertical cristae of the mouse, rat, and gerbil have an eminentia cruciatum, a
      region located transversely along the midpoint of the sensory organ and
      consisting of nonsensory cells. Apart from this eminentia cruciatum, there are no
      statistical differences between horizontal and vertical cristae with regard to
      area, width, length, the number and type of hair cells, and number of calretinin
      labeled calyx afferents.

PMID- 15240769
TI  - Taste receptor cells express pH-sensitive leak K+ channels.
AB  - Two-pore domain K+ channels encoded by genes KCNK1-17 (K2p1-17) play important
      roles in regulating cell excitability. We report here that rat taste receptor
      cells (TRCs) highly express TASK-2 (KCNK5; K2p5.1), and to a much lesser extent
      TALK-1 (KCNK16; K2p16.1) and TASK-1 (KCNK3; K2p3.1), and suggest potentially
      important roles for these channels in setting resting membrane potentials and in
      sour taste transduction. Whole cell recordings of isolated TRCs show that a leak
      K+ (Kleak) current in a subset of TRCs exhibited high sensitivity to acidic
      extracellular pH similar to reported properties of TASK-2 and TALK-1 channels. A
      drop in bath pH from 7.4 to 6 suppressed 90% of the current, resulting in
      membrane depolarization. K+ channel blockers, BaCl2, but not tetraethylammonium
      (TEA), inhibited the current. Interestingly, resting potentials of these TRCs
      averaged -70 mV, which closely correlated with the amplitude of the pH-sensitive
      Kleak, suggesting a dominant role of this conductance in setting resting
      potentials. RT-PCR assays followed by sequencing of PCR products showed that TASK
      1, TASK-2, and a functionally similar channel, TALK-1, were expressed in all
      three types of lingual taste buds. To verify expression of TASK channels, we
      labeled taste tissue with antibodies against TASK-1, TASK-2, and TASK-3. Strong
      labeling was seen in some TRCs with antibody against TASK-2 but not TASK-1 and
      TASK-3. Consistent with the immunocytochemical staining, quantitative real-time
      PCR assays showed that the message for TASK-2 was expressed at significantly
      higher levels (10-100 times greater) than was TASK-1, TALK-1, or TASK-3. Thus
      several K2P channels, and in particular TASK-2, are expressed in rat TRCs, where
      they may contribute to the establishment of resting potentials and sour
      reception.

PMID- 15240770
TI  - Metabotropic glutamate receptor-mediated depression of the slow
      afterhyperpolarization is gated by tyrosine phosphatases in hippocampal CA1
      pyramidal neurons.
AB  - Group I metabotropic glutamate receptor (mGluR) agonists increase the
      excitability of hippocampal CAl pyramidal neurons via depression of the postspike
      afterhyperpolarization. In adult rats, this is mediated by both mGluR1 and -5,
      but the signal transduction processes involved are unknown. In this study, we
      investigated whether altered levels of tyrosine phosphorylation of proteins are
      involved in the depression of the slow-duration afterhyperpolarization (sAHP) by
      the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in CA1 pyramidal
      neurons of rat hippocampal slices. Preincubation with the tyrosine kinase
      inhibitors lavendustin A or genistein, or the Src-specific inhibitor 3-(4
      chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2),
      did not inhibit the DHPG-mediated depression of the sAHP. However, preincubation
      with the tyrosine phosphatase inhibitor orthovanadate reduced the effects of
      DHPG. This effect of orthovanadate was prevented by simultaneous inhibition of
      tyrosine kinases with lavendustin A. Selective activation of either mGluR1 or -5
      by application of DHPG plus either the mGluR5 antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP) or the mGluR1 antagonist (S)-(+)-alpha-amino-4
      carboxy-2-methylbenzeneacetic acid (LY367385) demonstrated that the effect of
      inhibiting tyrosine phosphatases is not specific to either subtype of mGluR.
      These results suggest that the depression of the sAHP induced by activation of
      mGluR1 and -5 is gated by a balance between tyrosine phosphorylation and
      dephosphorylation.

PMID- 15240771
TI  - Nontoxicity endpoints in phase I trial designs for targeted, non-cytotoxic
      agents.

PMID- 15240772
TI  - How does human papillomavirus contribute to head and neck cancer development?

PMID- 15240773
TI  - Evolving strategies for targeted cancer therapy--past, present, and future.

PMID- 15240774
TI  - Running interference: pace picks up on synthetic lethality research.

PMID- 15240775
TI  - Directive threatens clinical research in Europe, critics say.

PMID- 15240776
TI  - Hearing addresses condoms for HPV prevention.

PMID- 15240778
TI  - BRCA1 discovery led to patent debate, genetic screening.

PMID- 15240779
TI  - Chew on this: mutation may be responsible for tooth loss, colon cancer.

PMID- 15240780
TI  - Stat bite: Trends in cancer mortality by primary cancer site, 1992-2001.

PMID- 15240782
TI  - Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents:
      theory and practice.
AB  - BACKGROUND: New targeted, non-cytotoxic anticancer agents, such as small-molecule
      kinase inhibitors, pose challenges to the current phase I paradigm of dose
      selection based on toxicity. Moreover, increasing the drug dose to toxicity may
      be unnecessary for drug effect, making the use of maximum tolerated dose as a
      surrogate of effective dose inappropriate in the phase I setting. Because little
      is known about the optimal methods of recommended phase II dose selection of
      targeted, non-cytotoxic therapies, we reviewed the strategies that were used in
      completed phase I studies of these drugs. METHODS: We retrieved 60 publications
      of phase I studies involving 31 single agents representative of the most common
      targets of interest in the oncology literature. For each publication, we
      abstracted data regarding patient population, starting dose, methods of dose
      escalation and determination of recommended phase II dose, and inclusion of
      correlative studies in study conduct. RESULTS: Of the 60 completed phase I
      studies, 36 used toxicity and eight used pharmacokinetic data as endpoints for
      selection of the recommended phase II dose. Nontraditional endpoints, such as
      measures of molecular drug effects in tumor or surrogate tissue or functional
      imaging studies, were not routinely incorporated into the study design and rarely
      formed the primary basis for dose selection. CONCLUSIONS: To date, phase I
      studies of targeted anticancer agents have generally used traditional endpoints
      for selection of the recommended phase II dose. More research is needed to define
      suitable molecular measures of drug effect and the means to incorporate them in
      the early drug development process.

PMID- 15240783
TI  - Genetic patterns in head and neck cancers that contain or lack transcriptionally
      active human papillomavirus.
AB  - BACKGROUND: Transcriptionally active high-risk human papilloma viruses (HPVs),
      particularly HPV type 16 (HPV16), are found in a subset of head and neck squamous
      cell carcinomas (HNSCCs). HPV16-associated carcinogenesis is mediated by
      expression of the viral E6 and E7 oncoproteins, which cause deregulation of the
      cell cycle by inactivating p53 and pRb, respectively. We tested the hypothesis
      that HPV-associated HNSCCs display a pattern of genetic alterations different
      from those of HNSCCs without HPV DNA. METHODS: Polymerase chain reaction-based
      assays were used to examine 143 consecutive HNSCCs (106 of the oral cavity and 37
      of the oropharynx) for the presence of HPV DNA and for viral E6 and/or E7
      messenger RNA (mRNA) expression. The HPV DNA-and E6 and E7 mRNA-positive HNSCCs
      and an equal number of HPV DNA-negative HNSCCs were further analyzed for
      mutations in TP53, the gene encoding p53, and for allelic loss of 28
      microsatellite markers at chromosome arms 3p, 6q, 8p, 9p, 13q, 17p, and 18q,
      including markers located in regions of chromosome arms 9p and 17p that harbor
      genes involved the p53 and pRb pathways. All statistical tests were two-sided.
      RESULTS: Twenty-four (16.7%) of the 143 HNSCCs were positive for HPV16 DNA, and
      12 of these HNSCCs (8.4% of total number) expressed E6 and E7 mRNAs. None of the
      HPV DNA-and E6/E7 mRNA-positive tumors had TP53 gene mutations, whereas nine
      (75%) of the 12 HPV DNA-negative tumors had such mutations (P<.001). Compared
      with the HPV DNA-negative HNSCCs, the E6/E7 mRNA-positive HNSCCs had
      statistically significantly lower levels of allelic loss for 13 of the 15 markers
      on 3p, 9p, and 17p. CONCLUSIONS: HNSCCs with transcriptionally active HPV16 DNA
      are characterized by occasional chromosomal loss, whereas HNSCCs lacking HPV DNA
      are characterized by gross deletions that involve whole or large parts of
      chromosomal arms and that already occur early in HNSCC development. These
      distinct patterns of genetic alterations suggest that HPV16 infection is an early
      event in HNSCC development.

PMID- 15240784
TI  - Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A
      associated medullary thyroid carcinoma.
AB  - BACKGROUND: The RET proto-oncogene encodes a receptor tyrosine kinase. RET
      oncogenes arise through sporadic and inherited gene mutations and are involved in
      the etiopathogenesis of medullary thyroid carcinoma, a cancer that responds
      poorly to conventional chemotherapy. Medullary thyroid carcinoma is a component
      of multiple endocrine neoplasia type 2 or MEN2 syndromes. METHODS: We
      investigated the cellular effects of RPI-1, a novel 2-indolinone Ret tyrosine
      kinase inhibitor on cells that express RET C634 oncogenic mutants common in the
      MEN2A syndrome: NIH3T3 fibroblasts transfected with RET(C634R) and human
      medullary thyroid carcinoma TT cells that express endogenous RET(C634W). RPI-1
      antiproliferative activity was determined by cell proliferation and anchorage
      independent growth assays. Expression and phosphorylation of Ret and of proteins
      involved in downstream signaling pathways were examined by immunoblotting.
      Antitumor activity of oral RPI-1 treatment was tested by using two dosing levels
      in nude mice bearing subcutaneous TT xenograft tumors. All statistical tests were
      two-sided. RESULTS: The RPI-1 IC50 value for cell proliferation was 3.6 microM
      (95% confidence interval [CI] = 1.8 to 5.4 microM) in NIH3T3 cells expressing the
      Ret mutant compared with 16 microM (95% CI = 12.3 to 19.7 microM) in non
      transfected NIH3T3 cells, and that for colony formation in soft agar was 2.4
      microM (95% CI = 0.8 to 4.0 microM) and 26 microM (95% CI = 17 to 35 microM) in
      RET mutant-transfected and H-RAS-transfected NIH3T3 cells, respectively. In
      NIH3T3 cells expressing the Ret mutant, Ret protein and tyrosine phosphorylation
      were undetectable after 24 hours of RPI-1 treatment. In TT cells, RPI-1 inhibited
      proliferation, Ret tyrosine phosphorylation, Ret protein expression, and the
      activation of PLCgamma, ERKs and AKT. In mice, oral daily RPI-1 treatment
      inhibited the tumor growth of TT xenografts by 81% (P<.001 versus control mice)
      and reduced the plasma levels of the specific biomarker calcitonin (P =.01 versus
      control mice). Twenty-five percent of RPI-1-treated mice were tumor-free.
      CONCLUSIONS: Ret oncoproteins represent exploitable targets for therapeutic
      intervention in MEN2A-associated medullary thyroid carcinoma. The antitumor
      efficacy and oral bioavailability of RPI-1 support its therapeutic potential.

PMID- 15240785
TI  - Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort
      studies.
AB  - BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of
      colorectal cancer. However, results from epidemiologic studies of intake of
      calcium or dairy foods and colorectal cancer risk have been inconclusive.
      METHODS: We pooled the primary data from 10 cohort studies in five countries that
      assessed usual dietary intake by using a validated food frequency questionnaire
      at baseline. For most studies, follow-up was extended beyond that in the original
      publication. The studies included 534 536 individuals, among whom 4992 incident
      cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up.
      Pooled multivariable relative risks for categories of milk intake and quintiles
      of calcium intake and 95% confidence intervals (CIs) were calculated. All
      statistical tests were two-sided. RESULTS: Milk intake was related to a reduced
      risk of colorectal cancer. Compared with the lowest category of intake (<70
      g/day), relative risks of colorectal cancer for increasing categories (70-174,
      175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02),
      0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively
      (P(trend)<.001). Calcium intake was also inversely related to the risk of
      colorectal cancer. The relative risk for the highest versus the lowest quintile
      of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) =.02) for dietary calcium and
      0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary
      and supplemental sources). These results were consistent across studies and sex.
      The inverse association for milk was limited to cancers of the distal colon
      (P(trend)<.001) and rectum (P(trend) =.02). CONCLUSION: Higher consumption of
      milk and calcium is associated with a lower risk of colorectal cancer.

PMID- 15240786
TI  - Genotoxicity of acrylamide and glycidamide.
AB  - BACKGROUND: Acrylamide, a known rodent carcinogen, is found in the human diet.
      However, the mechanism by which acrylamide exerts its carcinogenic effects
      remains unclear. METHODS: Normal human bronchial epithelial cells and Big Blue
      mouse embryonic fibroblasts that carry a lambda phage cII transgene were treated
      in vitro with acrylamide, its primary epoxide metabolite glycidamide, or water
      (control) and then subjected to terminal transferase-dependent polymerase chain
      reaction to map the formation of DNA adducts within the human gene encoding p53
      (TP53) and the cII transgene. The frequency and spectrum of glycidamide-induced
      mutations in cII were examined by using a lambda phage-based mutation detection
      system and DNA sequence analysis, respectively. All statistical tests were two
      sided. RESULTS: Acrylamide and glycidamide formed DNA adducts at similar specific
      locations within TP53 and cII, and DNA adduct formation was more pronounced after
      glycidamide treatment than after acrylamide treatment at all doses tested.
      Acrylamide-DNA adduct formation was saturable, whereas the formation of most
      glycidamide-DNA adducts was dose-dependent. Glycidamide treatment dose
      dependently increased the frequency of cII mutations relative to control
      treatment (P<.001). Glycidamide was more mutagenic than acrylamide at any given
      dose. The spectrum of glycidamide-induced cII mutations was statistically
      significantly different from the spectrum of spontaneously occurring mutations in
      the control-treated cells (P=.038). Compared with spontaneous mutations in
      control cells, cells treated with glycidamide or acrylamide had more A-->G
      transitions and G-->C transversions and glycidamide-treated cells had more G-->T
      transversions (P<.001). CONCLUSION: The mutagenicity of acrylamide in human and
      mouse cells is based on the capacity of its epoxide metabolite glycidamide to
      form DNA adducts.

PMID- 15240787
TI  - Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell
      carcinoma.
AB  - BACKGROUND: The FAS receptor-ligand system is a key regulator of apoptotic cell
      death, and loss of FAS expression and gain of FAS ligand (FASL) expression play
      important roles in the development and progression of cancer. Single-nucleotide
      polymorphisms in the promoter region of the FAS (G or A at position -1377 [FAS 
      1377G/A] and A or G at position -670 [FAS -670A/G]) and FASL (T or C at position 
      844 [FASL -844T/C]) genes alter the transcriptional activity of these genes. We
      examined the association between these polymorphisms and risk of the development
      and metastasis of esophageal squamous-cell carcinoma. METHODS: Genotypes of 588
      case patients with esophageal squamous-cell carcinoma and 648 control subjects
      were determined by polymerase chain reaction-based restriction fragment length
      polymorphism. Associations with the risk of esophageal squamous-cell carcinoma
      were estimated by logistic regression. All statistical tests were two-sided.
      RESULTS: We observed a statistically significantly increased risk of esophageal
      squamous-cell carcinoma associated with the FAS -1377AA (odds ratio [OR] = 1.79,
      95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS -670GG (OR = 1.72,
      95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage
      disequilibrium compared with the FAS -1377GA or GG or the FAS -670AG or AA
      genotype, respectively. An increased risk of esophageal squamous-cell carcinoma
      was also associated with the FASL -844CC genotype (OR = 2.06, 95% CI = 1.64 to
      2.59; P<.001) compared with the FASL -844CT or TT genotype. Gene-gene
      interactions of FAS and FASL polymorphisms increased the risk of esophageal
      squamous-cell carcinoma in a multiplicative manner (OR for the presence of both
      FAS -1377AA and FASL -844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P =.001,
      test for homogeneity). Statistically significant interactions were found between
      these polymorphisms in FAS and FASL and tobacco smoking. None of the
      polymorphisms was associated with risk of differentiation or metastasis of
      esophageal squamous-cell carcinoma at diagnosis. CONCLUSION: Genetic
      polymorphisms in the death pathway genes FAS and FASL appear to be associated
      with an increased risk of developing esophageal squamous-cell carcinoma.

PMID- 15240788
TI  - Re: Extended follow-up of a cohort of British chemical workers exposed to
      formaldehyde.

PMID- 15240790
TI  - Re: Consolidation therapy with autologous bone marrow transplantation in adults
      with acute myeloid leukemia: a meta-analysis.

PMID- 15240792
TI  - Re: Estrogen receptor status of primary breast cancer is predictive of estrogen
      receptor status of contralateral breast cancer.

PMID- 15240794
TI  - Re: Active smoking, household passive smoking, and breast cancer: evidence from
      the California Teachers Study.

PMID- 15240796
TI  - Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term
      potentiation induction involves activation of microglia and stimulation of
      inducible nitric oxide synthase and superoxide.
AB  - The mechanisms underlying the inhibition of long-term potentiation (LTP)
      induction by amyloidbeta-peptide (Abeta) were investigated in the medial
      perforant path of the rat and mouse dentate gyrus in vitro. Evidence is presented
      in this study that the Abeta-mediated inhibition of LTP induction involves
      activation of microglia and production of reactive oxygen and nitrogen species.
      In control slices, Abeta strongly inhibited induction of NMDA receptor-dependent
      (NMDAR-dependent) LTP, although not induction of NMDAR-independent LTP or long
      term depression (LTD). The inhibition of NMDAR-dependent LTP was prevented by
      minocycline, an agent that prevents activation of microglia. The involvement of
      inducible nitric oxide synthase (iNOS) was shown by the inability of Abeta to
      inhibit LTP induction in iNOS knock-out mice and also by the ability of two iNOS
      inhibitors, aminoguanidine and 1400W, to prevent the Abeta-mediated inhibition of
      LTP induction. The Abeta-mediated inhibition of LTP induction also was prevented
      by the superoxide scavenger superoxide dismutase applied together with catalase.
      Evidence for involvement of superoxide in the action of Abeta on LTP induction
      was shown by the ability of an inhibitor of NADPH oxidase to prevent the Abeta
      mediated inhibition of LTP induction. The study thus provides evidence that the
      Abeta-mediated inhibition of LTP induction involves an inflammatory-type reaction
      in which activation of microglia results in the production of nitric oxide and
      superoxide and thence possibly peroxynitrite, a highly reactive oxidant.

PMID- 15240797
TI  - Fibroblast growth factor receptor 1 is required for the proliferation of
      hippocampal progenitor cells and for hippocampal growth in mouse.
AB  - Fibroblast growth factor receptor 1 (Fgfr1) is expressed at high levels by
      progenitor cells of the ventricular zone (VZ) within the hippocampal primordium.
      To investigate the role of Fgfr1 in these cells, in vivo Cre recombination of
      "floxed" Fgfr1 alleles was directed to cells of the radial glial lineage by using
      the human glial fibrillary acidic protein promoter. Radial glial-like cells of
      the hippocampal VZ are the progenitors of pyramidal neurons and granule cells of
      hippocampal dentate gyrus (DG). Mice carrying null Fgfr1 alleles
      (Fgfr1(Deltaflox)) in cells of this lineage showed a dramatic loss of Fgfr1 gene
      expression throughout the embryonic dorsal telencephalon. These Fgfr1(Deltaflox)
      mice exhibited a approximately 30% decrease in dividing radial glial progenitor
      cells in the hippocampal VZ and DG in the late embryonic period, progressing to a
      approximately 50-60% loss at birth, without any changes in cell survival. In
      addition, no FGF2-sensitive neural stem cells could be isolated from the
      Fgfr1(Deltaflox) hippocampal neuroepithelium, whereas epidermal growth factor
      sensitive neural stem cells were not affected. The number of hippocampal
      pyramidal neurons and DG granule cells was approximately 30-50% decreased from
      the perinatal period through adulthood, and the number of parvalbumin-containing
      interneurons was similarly decreased in both the DG and pyramidal cell fields. We
      conclude that Fgfr1 is necessary for hippocampal growth, because it promotes the
      proliferation of hippocampal progenitors and stem cells during development.

PMID- 15240798
TI  - Odorant-evoked nitric oxide signals in the antennal lobe of Manduca sexta.
AB  - The gaseous signaling molecule nitric oxide (NO) can affect the activities of
      neurons and neural networks in many different systems. The strong expression of
      NO synthase (NOS) in the primary synaptic neuropil (the antennal lobe in insects
      and the olfactory bulb in vertebrates) of the olfactory system of most organisms,
      and the unique spheroidal geometry of olfactory glomeruli in those neuropils,
      have led to suggestions that NO signaling is important for processing olfactory
      information. No direct evidence exists, however, that NO signals are produced in
      olfactory glomeruli. We investigated the production of NO in the antennal lobe of
      the moth, Manduca sexta, by using immunocytochemistry and real-time optical
      imaging with a NO-sensitive fluorescent marker, diaminofluorescein diacetate. We
      confirmed that NOS was expressed in the axons of olfactory receptor neurons
      projecting to all glomeruli. Soluble guanylyl cyclase, the best characterized
      target of NO, was found in a subset of postsynaptic antennal lobe neurons that
      included projection neurons, a small number of GABA-immunoreactive neurons, and a
      serotonin-immunoreactive neuron. We found that odorant stimulation evoked NO
      signals that were reproducible and spatially focused. Different odorants evoked
      spatially distinct patterns of NO production. Increased concentrations of
      pheromone and plant odorants caused increases in peak signal intensity. Increased
      concentrations of plant odorants also evoked a dramatic increase in signal area.
      The results of these experiments show clearly that odorant stimulation can evoke
      NO production in the olfactory system. The NO signals produced are likely to play
      an important role in processing olfactory information.

PMID- 15240799
TI  - The Y99C mutation in guanylyl cyclase-activating protein 1 increases
      intracellular Ca2+ and causes photoreceptor degeneration in transgenic mice.
AB  - Guanylyl cyclase-activating proteins (GCAPs) are Ca2+-binding proteins that
      activate guanylyl cyclase when free Ca2+ concentrations in retinal rods and cones
      fall after illumination and inhibit the cyclase when free Ca2+ reaches its
      resting level in the dark. Several forms of retinal dystrophy are caused by
      mutations in GUCA1A, the gene coding for GCAP1. To investigate the cellular
      mechanisms affected by the diseased state, we created transgenic mice that
      express GCAP1 with a Tyr99Cys substitution (Y99C GCAP1) found in human patients
      with a late-onset retinal dystrophy (Payne et al., 1998). Y99C GCAP1 shifted the
      Ca2+ sensitivity of the guanylyl cyclase in photoreceptors, keeping it partially
      active at 250 nM free Ca2+, the normal resting Ca2+ concentration in darkness.
      The enhanced activity of the cyclase in the dark increased cyclic nucleotide
      gated channel activity and elevated the rod outer segment Ca2+ concentration in
      darkness, measured by using fluo-5F and laser spot microscopy. In different lines
      of transgenic mice the magnitude of this effect rose with the Y99C GCAP1
      expression. Surprisingly, there was little change in the rod photoresponse,
      indicating that dynamic Ca2+-dependent regulation of cGMP synthesis was
      preserved. However, the photoreceptors in these mice degenerated, and the rate of
      the cell loss increased with the level of the transgene expression, unlike in
      transgenic mice that overexpressed normal GCAP1. These results provide the first
      direct evidence that a mutation linked to congenital blindness increases Ca2+ in
      the outer segment, which may trigger the apoptotic process.

PMID- 15240800
TI  - Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)
      deficient mice.
AB  - GABAB receptors mediate slow synaptic inhibition in the nervous system. In
      transfected cells, functional GABAB receptors are usually only observed after
      coexpression of GABAB(1) and GABAB(2) subunits, which established the concept of
      heteromerization for G-protein-coupled receptors. In the heteromeric receptor,
      GABAB(1) is responsible for binding of GABA, whereas GABAB(2) is necessary for
      surface trafficking and G-protein coupling. Consistent with these in vitro
      observations, the GABAB(1) subunit is also essential for all GABAB signaling in
      vivo. Mice lacking the GABAB(1) subunit do not exhibit detectable
      electrophysiological, biochemical, or behavioral responses to GABAB agonists.
      However, GABAB(1) exhibits a broader cellular expression pattern than GABAB(2),
      suggesting that GABAB(1) could be functional in the absence of GABAB(2). We now
      generated GABAB(2)-deficient mice to analyze whether GABAB(1) has the potential
      to signal without GABAB(2) in neurons. We show that GABAB(2)-/- mice suffer from
      spontaneous seizures, hyperalgesia, hyperlocomotor activity, and severe memory
      impairment, analogous to GABAB(1)-/- mice. This clearly demonstrates that the
      lack of heteromeric GABAB(1,2) receptors underlies these phenotypes. To our
      surprise and in contrast to GABAB(1)-/- mice, we still detect atypical
      electrophysiological GABAB responses in hippocampal slices of GABAB(2)-/- mice.
      Furthermore, in the absence of GABAB(2), the GABAB(1) protein relocates from
      distal neuronal sites to the soma and proximal dendrites. Our data suggest that
      association of GABAB(2) with GABAB(1) is essential for receptor localization in
      distal processes but is not absolutely necessary for signaling. It is therefore
      possible that functional GABAB receptors exist in neurons that naturally lack
      GABAB(2) subunits.

PMID- 15240801
TI  - Dendroarchitecture and lateral inhibition in thalamic barreloids.
AB  - Thalamic cells that relay vibrissa information to barrel cortex are clustered
      within whisker-related modules termed barreloids. Each barreloid receives input
      from one principal whisker and inhibitory inputs from reticular thalamic neurons
      with receptive fields that correspond to that same whisker. Although the proximal
      dendrites of relay cells are confined to their home barreloid, distal dendrites
      often extend into surrounding barreloids representing adjacent whiskers on the
      mystacial pad. It was proposed that this arrangement provides a substrate for a
      mechanism of lateral inhibition that operates remotely on extrabarreloid
      dendrites. In the present study, we identified adjacent whiskers that suppressed
      activity below background levels in barreloid cells, and we used a double
      labeling protocol to relate the efficacy of inhibition to the dendroarchitecture
      of the cells. Significant suppression of background discharges was produced by
      92% of adjacent whiskers within rows, by 48% of adjacent whiskers within arcs,
      but was never observed after deflection of nonadjacent whiskers. The magnitude of
      lateral inhibition increases linearly as the cumulated length of dendrites
      increases in the barreloid representing an adjacent whisker (R2 = 0.86; p <
      0.0001). As distance between cell bodies and the border of an adjacent barreloid
      increases, dendritic length in that adjacent barreloid diminishes and so does
      inhibition. Considering time differences between the arrival of principal and
      adjacent whisker inputs in barreloids, our data suggest that inhibition operating
      distally on dendrites acts as a spatial filter that primarily suppresses adjacent
      whisker inputs and so contributes to enhance edge detection.

PMID- 15240802
TI  - The influence of sustained selective attention on stimulus selectivity in macaque
      visual area MT.
AB  - Remarkable alterations of perception during long-lasting attentional processes
      have been described in several recent studies. Although these findings have
      gained much interest, almost nothing is known about the modulation of neuronal
      responses during sustained attention. Therefore, we investigated the effect of
      prolonged selective attention on neuronal feature selectivity. Awake macaque
      monkeys were trained to perform a motion-tracking task that required attending
      one of two simultaneously presented moving bars for up to 15 sec. Extracellular
      recordings were obtained from neurons in macaque motion-sensitive middle temporal
      visual area (MT/V5). Under conditions of attention, we found high and constant
      direction selectivity over time. This was expressed by a strong and persistent
      response contrast between presentations of preferred and nonpreferred stimuli in
      successive motion cycles. With attention directed to another moving bar, neuronal
      responses to the behaviorally irrelevant stimulus became continuously less
      specific for the direction of motion. In particular, increasingly higher firing
      rates for motion in null direction caused a strong reduction of direction
      selectivity, which further increased with enhanced proximity between target and
      distracter bar. A passive condition experiment revealed that this reduction
      occurred only when motion remained the behaviorally relevant feature but
      disappeared when attention was withdrawn from this feature domain. Thus,
      sustained attention seems to stabilize direction selectivity of neurons in area
      MT against a time and competition-dependent degradation, whereas nonattended
      objects suffer from a reduced neuronal representation.

PMID- 15240803
TI  - cAMP response element-binding protein, activating transcription factor-4, and
      upstream stimulatory factor differentially control hippocampal GABABR1a and
      GABABR1b subunit gene expression through alternative promoters.
AB  - Expression of metabotropic GABA(B) receptors is essential for slow inhibitory
      synaptic transmission in the CNS, and disruption of GABA(B) receptor-mediated
      responses has been associated with several disorders, including neuropathic pain
      and epilepsy. The location of GABA(B) receptors in neurons determines their
      specific role in synaptic transmission, and it is believed that sorting of
      subunit isoforms, GABA(B)R1a and GABA(B)R1b, to presynaptic or postsynaptic
      membranes helps to determine this role. GABA(B)R1a and GABA(B)R1b are thought to
      arise by alternative splicing of heteronuclear RNA. We now demonstrate that
      alternative promoters, rather than alternative splicing, produce GABA(B)R1a and
      GABA(B)R1b isoforms. Our data further show that subunit gene expression in
      hippocampal neurons is mediated by the cAMP response element-binding protein
      (CREB) by binding to unique cAMP response elements in the alternative promoter
      regions. Double-stranded oligonucleotide decoys selectively alter levels of
      endogenous GABA(B)R1a and GABA(B)R1b in primary hippocampal neurons, and CREB
      knock-out mice show changes in levels of GABA(B)R1a and GABA(B)R1b transcripts,
      consistent with decoy competition experiments. These results demonstrate a
      critical role of CREB in transcriptional mechanisms that control GABA(B)R1
      subunit levels in vivo. In addition, the CREB-related factor activating
      transcription factor-4 (ATF4) has been shown to interact directly with GABA(B)R1
      in neurons, and we show that ATF4 differentially regulates GABA(B)R1a and
      GABA(B)R1b promoter activity. These results, together with our finding that the
      depolarization-sensitive upstream stimulatory factor (USF) binds to a composite
      CREB/ATF4/USF regulatory element only in the absence of CREB binding, indicate
      that selective control of alternative GABA(B)R1 promoters by CREB, ATF4, and USF
      may dynamically regulate expression of their gene products in the nervous system.

PMID- 15240804
TI  - Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons.
AB  - We have asked whether loss of the Ca2+ sensor protein synaptotagmin I influences
      the total amount of neurotransmitter released after a presynaptic action
      potential. Hippocampal neurons from synaptotagmin I knock-out mice had a greatly
      reduced fast synchronous component of glutamate release, as reported previously.
      However, the amount of glutamate released during the slow asynchronous component
      increased in these knock-out neurons. As a result of these changes in the
      kinetics of release, there was no significant difference between wild-type and
      knock-out neurons in the total amount of transmitter released within 400 msec
      after a presynaptic stimulus. Fluorescence imaging experiments demonstrated that
      wild-type and knock-out neurons take up and release similar amounts of FM dye
      after depolarization, indicating normal amounts of synaptic vesicle trafficking
      in the knock-out neurons. These results indicate that synaptotagmin I knock-out
      neurons are fully capable of releasing neurotransmitter, with the increased slow
      component of release serving to compensate for loss of the fast component. Thus,
      synaptotagmin I synchronizes the rapid release of neurotransmitters after Ca2+
      entry into presynaptic terminals and also appears to suppress the slower,
      asynchronous form of transmitter release.

PMID- 15240805
TI  - Dopamine, through the extracellular signal-regulated kinase pathway,
      downregulates CD4+CD25+ regulatory T-cell activity: implications for
      neurodegeneration.
AB  - Fighting off neuronal degeneration requires a well controlled T-cell response
      against self-antigens residing in sites of the CNS damage. The ability to evoke
      this response is normally suppressed by naturally occurring CD4+CD25+ regulatory
      T-cells (Treg). No physiological compound that controls Treg activity has yet
      been identified. Here, we show that dopamine, acting via type 1 dopamine
      receptors (found here to be preferentially expressed by Treg), reduces the
      suppressive activity and the adhesive and migratory abilities of Treg. Treg
      activity was correlated with activation of the ERK1/2 (extracellular signal
      regulated kinase 1/2) signaling pathway. Systemic injection of dopamine or an
      agonist of its type 1 receptors significantly enhanced, via a T-cell-dependent
      mechanism, protection against neuronal death after CNS mechanical and biochemical
      injury. These findings shed light on the physiological mechanisms controlling
      Treg and might open the way to novel therapeutic strategies for downregulating
      Treg activity (e.g., in neuronal degeneration) or for strengthening it (in
      autoimmune diseases).

PMID- 15240806
TI  - Passive amyloid immunotherapy clears amyloid and transiently activates microglia
      in a transgenic mouse model of amyloid deposition.
AB  - The role of microglia in the removal of amyloid deposits after systemically
      administered anti-Abeta antibodies remains unclear. In the current study, we
      injected Tg2576 APP transgenic mice weekly with an anti-Abeta antibody for 1, 2,
      or 3 months such that all mice were 22 months at the end of the study. In mice
      immunized for 3 months, we found an improvement in alternation performance in the
      Y maze. Histologically, we were able to detect mouse IgG bound to congophilic
      amyloid deposits in those mice treated with the anti-Abeta antibody but not in
      those treated with a control antibody. We found that Fcgamma receptor expression
      on microglia was increased after 1 month of treatment, whereas CD45 was increased
      after 2 months of treatment. Associated with these microglial changes was a
      reduction in both diffuse and compact amyloid deposits after 2 months of
      treatment. Interestingly, the microglia markers were reduced to control levels
      after 3 months of treatment, whereas amyloid levels remained reduced. Serum Abeta
      levels and anti-Abeta antibody levels were elevated to similar levels at all
      three survival times in mice given anti-Abeta injections rather than control
      antibody injections. These data show that the antibody is able to enter the brain
      and bind to the amyloid deposits, likely opsonizing the Abeta and resulting in
      Fcgamma receptor-mediated phagocytosis. Together with our earlier work, our data
      argue that all proposed mechanisms of anti-Abeta antibody-mediated amyloid
      removal can be simultaneously active.

PMID- 15240807
TI  - Tyrosine phosphorylation and regulation of the AMPA receptor by SRC family
      tyrosine kinases.
AB  - Phosphorylation of AMPA receptors is a major mechanism for the regulation of
      receptor function and underlies several forms of synaptic plasticity in the CNS.
      Although serine and threonine phosphorylation of AMPA receptors has been well
      studied, the potential role of tyrosine phosphorylation of AMPA receptors has not
      been investigated. Here, we show that the GluR2 subunit of AMPA receptors is
      tyrosine phosphorylated in vitro and in vivo by Src family tyrosine kinases on
      tyrosine 876 near its C terminus. In addition, GluR agonist treatment of cultured
      cortical neurons increased phosphorylation of tyrosine 876. The association with
      GluR2-interacting molecules GRIP1/2 was decreased by tyrosine phosphorylation of
      GluR2, whereas PICK1 interaction was not influenced. Moreover, mutation of
      tyrosine 876 eliminated AMPA- and NMDA-induced internalization of the GluR2
      subunit. These data indicate that tyrosine phosphorylation of tyrosine 876 on the
      GluR2 C terminus by Src family tyrosine kinases is important for the regulation
      of AMPA receptor function and may be important for synaptic plasticity.

PMID- 15240808
TI  - Correlation between semaphorin3A-induced facilitation of axonal transport and
      local activation of a translation initiation factor eukaryotic translation
      initiation factor 4E.
AB  - An impressive body of evidence has been accumulated indicating that local protein
      synthesis is implicated in navigation of neurite extension induced by guidance
      cues, such as semaphorin3A (Sema3A). We found previously that a Src type tyrosine
      kinase Fyn and cyclin-dependent kinase 5 (Cdk5) mediate Sema3A-signaling. We also
      showed that Sema3A elicits axonal transport through neuropilin-1, a receptor for
      Sema3A, located at the growth cones. Here, we investigate the relationship
      between Sema3A-induced local signaling, protein synthesis, and axonal transport.
      Lavendustin A, a tyrosine kinase inhibitor, and olomoucine, a cyclin-dependent
      kinase inhibitor, suppressed Sema3A-induced facilitation of anterograde and
      retrograde axonal transport in dorsal root ganglion (DRG) neuron with and without
      the cell body. Sema3A-induced facilitation of axonal transport was attenuated in
      DRG neurons of fyn- (fyn-/-) and a Cdk5 activator, p35 (p35-/-)-deficient mice
      when compared with those of wild-type or heterozygous mice. Inhibition of protein
      synthesis suppressed Sema3A-induced facilitation of axonal transport in the DRG
      neuron with and without the cell body. Sema3A enhanced the level of
      immunoreactivity of phosphorylated eukaryotic translation initiation factor 4E
      (eIF-4E) within 5 min in growth cones in a time course similar to that of the
      facilitated axonal transport. This enhanced signal for phospho-eIF4E was blocked
      by lavendustin A or olomoucine and was not detected in the fyn-/- and p35-/-
      neurons. These results provide evidence for a mutual regulatory mechanism between
      local protein synthesis and axonal transport.

PMID- 15240809
TI  - Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor:
      the asymmetric trapping block model.
AB  - The NMDA receptor (NMDAR) produces a long-lasting component of the glutamatergic
      EPSC in mammalian central neurons. The current through NMDARs is voltage
      dependent as a result of block by extracellular magnesium, which has recently
      been shown to give rise to a complex time dependence, with fast and slow
      components of responses to changes in membrane potential. Here, we studied the
      dynamics of block and unblock by measuring voltage step responses in conjunction
      with fast perfusion of agonist in nucleated patches isolated from rat cortical
      pyramidal neurons. We found that slow unblock shows a progressive onset during
      synaptic-like responses to brief pulses of agonist. Repolarizing briefly from +40
      to -70 mV revealed that slow unblock is reestablished with a time constant of
      approximately 5 msec at room temperature. Also, the time course of deactivation,
      in response to a pulse of agonist, slows twofold over the potential range -30 to
      +40 mV. An asymmetric "trapping block" model in which the voltage-independent
      closing rate constant of the blocked channel is approximately three times that of
      the unblocked channel accounts quantitatively for all of these phenomena and for
      responses to action potential waveform clamp. This model allows much more
      accurate prediction of NMDAR current in physiological conditions of magnesium
      concentration and changing membrane potential than previously possible. It
      suggests a positive allosteric link between occupation of the NMDAR pore by
      magnesium and closure of the permeation gate.

PMID- 15240810
TI  - Point-light biological motion perception activates human premotor cortex.
AB  - Motion cues can be surprisingly powerful in defining objects and events.
      Specifically, a handful of point-lights attached to the joints of a human actor
      will evoke a vivid percept of action when the body is in motion. The perception
      of point-light biological motion activates posterior cortical areas of the brain.
      On the other hand, observation of others' actions is known to also evoke activity
      in motor and premotor areas in frontal cortex. In the present study, we
      investigated whether point-light biological motion animations would lead to
      activity in frontal cortex as well. We performed a human functional magnetic
      resonance imaging study on a high-field-strength magnet and used a number of
      methods to increase signal, as well as cortical surface-based analysis methods.
      Areas that responded selectively to point-light biological motion were found in
      lateral and inferior temporal cortex and in inferior frontal cortex. The robust
      responses we observed in frontal areas indicate that these stimuli can also
      recruit action observation networks, although they are very simplified and
      characterize actions by motion cues alone. The finding that even point-light
      animations evoke activity in frontal regions suggests that the motor system of
      the observer may be recruited to "fill in" these simplified displays.

PMID- 15240811
TI  - Cloning of a novel Apaf-1-interacting protein: a potent suppressor of apoptosis
      and ischemic neuronal cell death.
AB  - Cytochrome c-initiated activation of apoptotic protease activating factor-1 (Apaf
      1) is a key step in the mitochondrial-signaling pathway for the activation of
      death-executing caspases in apoptosis. This signaling pathway has been implicated
      in the pathophysiology of various neurological disorders, including ischemic
      brain injury. In this study, we have cloned a novel rat gene product, designated
      as Apaf-1-interacting protein (AIP), which functions as a dominant-negative
      inhibitor of the Apaf-1-caspase-9 pathway. AIP is constitutively expressed in the
      brain, but at substantially lower levels than Apaf-1 and caspase-9. AIP can
      directly bind to Apaf-1 in vitro through its N-terminal caspase-recruiting
      domain, and this protein interaction was increased in cells undergoing apoptosis.
      Cytosolic extracts from cells overexpressing AIP were highly resistant to
      cytochrome c- dATP-induced activation of caspase-9 and caspase-3. Gene
      transfection of AIP into cell lines, including the neuronal-differentiated PC12
      cells, potently suppressed apoptosis induced by various pro-apoptotic stimuli. To
      further investigate the functional role of AIP in primary neurons and in the
      brain, an adeno-associated virus (AAV) vector carrying the AIP cDNA was
      constructed. AAV-mediated overexpression of AIP in primary cortical- hippocampal
      neurons markedly reduced cell death and caspase-3 activation triggered by protein
      kinase C inhibition, DNA damage, or oxygen- glucose deprivation. Moreover,
      intracerebral infusion of the AAV vector resulted in robust AIP expression in the
      hippocampus and significantly promoted CA1 neuronal survival after transient
      global cerebral ischemia. These results suggest that molecular targeting of the
      Apaf-1-caspase-9 signaling pathway may be a feasible neuroprotective strategy to
      enhance the endogenous threshold for caspase activation and prevent neuronal loss
      in stroke and related disorders.

PMID- 15240812
TI  - Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering
      neuroenergetics.
AB  - Increasing evidence suggests that glutamate activates the generation of lactate
      from glucose in astrocytes; this lactate is shuttled to neurons that use it as a
      preferential energy source. We explore this multicellular "lactate shuttle" with
      a novel dual-cell, dual-gene therapy approach and determine the neuroprotective
      potential of enhancing this shuttle. Viral vector-driven overexpression of a
      glucose transporter in glia enhanced glucose uptake, lactate efflux, and the
      glial capacity to protect neurons from excitotoxicity. In parallel,
      overexpression of a lactate transporter in neurons enhanced lactate uptake and
      neuronal resistance to excitotoxicity. Finally, overexpression of both transgenes
      in the respective cell types provided more protection than either therapy alone,
      demonstrating that a dual-cell, dual-gene therapy approach gives greater
      neuroprotection than the conventional single-cell, single-gene strategy.

PMID- 15240813
TI  - Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity.
AB  - After ischemic stroke, partial recovery of function frequently occurs and may
      depend on the plasticity of axonal connections. Here, we examine whether blockade
      of the Nogo-NogoReceptor (NgR) pathway might enhance axonal sprouting and thereby
      recovery after focal brain infarction. Mutant mice lacking NgR or Nogo-AB recover
      complex motor function after stroke more completely than do control animals.
      After a stroke, greater numbers of axons emanating from the undamaged cortex
      cross the midline to innervate the contralateral red nucleus and the ipsilateral
      cervical spinal cord; this axonal plasticity is enhanced in ngr -/- or nogo-ab -/
      mice. In rats with middle cerebral artery occlusion, both the recovery of motor
      skills and corticofugal axonal plasticity are promoted by intracerebroventricular
      administration of a function-blocking NgR fragment. Behavioral improvement occurs
      when therapy is initiated 1 week after arterial occlusion. Thus, delayed
      pharmacological blockade of the NgR promotes subacute stroke recovery by
      facilitating axonal plasticity.

PMID- 15240814
TI  - Rapid axoglial signaling mediated by neuregulin and neurotrophic factors.
AB  - During peripheral nervous system development, Schwann cells are precisely matched
      to the axons that they support. This is mediated by axonal neuregulins that are
      essential for Schwann cell survival and differentiation. Here, we show that
      sensory and motor axons rapidly release heparin-binding forms of neuregulin in
      response to Schwann cell-derived neurotrophic factors in a dose-dependent manner.
      Neuregulin release occurs within minutes, is saturable, and occurs from axons
      that were isolated using a newly designed chamber slide apparatus. Although NGF
      and glial cell line-derived neurotrophic factor (GDNF) were the most potent
      neurotrophic factors to release neuregulin from sensory neurons, GDNF and BDNF
      were most potent for motor neurons and were the predominant neuregulin-releasing
      neurotrophic factors produced by cultured Schwann cells. Comparable levels of
      neuregulin could be released at a similar rate from neurons after protein kinase
      C activation with the phorbol ester, phorbol 12-myristate 13-acetate, which has
      also been shown to promote the cleavage and release of neuregulin from its
      transmembrane precursor. The rapid release of neuregulin from axons in response
      to Schwann cell-derived neurotrophic factors may be part of a spatially
      restricted system of communication at the axoglial interface important for proper
      peripheral nerve development, function, and repair.

PMID- 15240815
TI  - Attenuated plasticity of postsynaptic kainate receptors in hippocampal CA3
      pyramidal neurons.
AB  - Kainate receptor-mediated components of postsynaptic currents at hippocampal
      mossy fiber synapses have markedly slower kinetics than currents arising from
      AMPA receptors. Here, we demonstrate that other aspects of kainate and AMPA
      receptor function at this synapse are distinct; in particular, kainate receptor
      currents are less sensitive to short- and long-term increases in presynaptic
      strength. EPSCs arising predominantly from AMPA receptors exhibited well
      characterized paired-pulse facilitation, frequency facilitation, and NMDA
      receptor-independent long-term potentiation, whereas isolated kainate receptor
      synaptic currents (KA-EPSCs) exhibited attenuated facilitation and long-term
      potentiation. In addition, KA-EPSCs varied in their sensitivity to a low-affinity
      competitive antagonist, suggestive of a synaptic heterogeneity greater than that
      of EPSCs comprised predominantly of AMPA receptors. These data suggest that the
      proportional contribution of AMPA and kainate receptors to ensemble synaptic
      currents will vary depending on the firing frequency of mossy fiber afferents.
      These synaptic features may be a mechanism for limiting activation of kainate
      receptors at mossy fiber synapses, which has been shown to be involved in
      seizurogenic firing of the CA3 network.

PMID- 15240816
TI  - In vivo reconstitution of the negative feedback in nitric oxide/cGMP signaling:
      role of phosphodiesterase type 5 phosphorylation.
AB  - Most effects of the messenger molecule nitric oxide (NO) are mediated by cGMP,
      which is formed by NO-sensitive guanylyl cyclase (GC) and degraded by
      phosphodiesterases (PDEs). In platelets, NO elicits a spike-like cGMP response
      and causes a sustained desensitization. Both characteristics have been attributed
      to PDE5 activation caused by cGMP binding to its regulatory GAF domain.
      Activation is paralleled by phosphorylation whose precise function remains
      unknown. Here, we report reconstitution of all features of the NO-induced cGMP
      response in human embryonic kidney cells by coexpressing NO-sensitive GC and
      PDE5. The spike-like cGMP response was blunted when PDE5 phosphorylation was
      enhanced by additional overexpression of cGMP-dependent protein kinase. Analysis
      of PDE5 activation in vitro revealed a discrepancy between the cGMP
      concentrations required for activation (micromolar) and reversal of activation
      (nanomolar), indicating the conversion of a low-affinity state to a high-affinity
      state upon binding of cGMP. Phosphorylation even increased the high apparent
      affinity enabling PDE5 activation to persist at extremely low cGMP
      concentrations. Our data suggest that the spike-like shape and the
      desensitization of the cGMP response are potentially inherent to every GC- and
      PDE5-expressing cell. Phosphorylation of PDE5 seems to act as memory switch for
      activation leading to long-term desensitization of the signaling pathway.

PMID- 15240817
TI  - Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair
      follicle development.
AB  - Members of the serum- and glucocorticoid-regulated kinase (SGK) family are
      important mediators of growth factor and hormone signaling that, like their close
      relatives in the Akt family, are regulated by lipid products of
      phosphatidylinositol-3-kinase. SGK3 has been implicated in the control of cell
      survival and regulation of ion channel activity in cultured cells. To begin to
      dissect the in vivo functions of SGK3, we generated and characterized Sgk3 null
      mice. These mice are viable and fertile, and in contrast to mice lacking SGK1 or
      Akt2, respectively, display normal sodium handling and glucose tolerance.
      However, although normal at birth, by postpartum day 4 they have begun to display
      an unexpected defect in hair follicle morphogenesis. The abnormality in hair
      follicle development is preceded by a defect in proliferation and nuclear
      accumulation of beta-catenin in hair bulb keratinocytes. Furthermore, in cultured
      keratinocytes, heterologous expression of SGK3 potently modulates activation of
      beta-catenin/Lef-1-mediated gene transcription. These data establish a role for
      SGK3 in normal postnatal hair follicle development, possibly involving effects on
      beta-catenin/Lef-1-mediated gene transcription.

PMID- 15240818
TI  - Oncostatin M-stimulated apical plasma membrane biogenesis requires p27(Kip1)
      regulated cell cycle dynamics.
AB  - Oncostatin M regulates membrane traffic and stimulates apicalization of the cell
      surface in hepatoma cells in a protein kinase A-dependent manner. Here, we show
      that oncostatin M enhances the expression of the cyclin-dependent kinase (cdk)2
      inhibitor p27(Kip1), which inhibits G(1)-S phase progression. Forced G(1)-S-phase
      transition effectively renders presynchronized cells insensitive to the
      apicalization-stimulating effect of oncostatin M. G(1)-S-phase transition
      prevents oncostatin M-mediated recruitment of protein kinase A to the centrosomal
      region and precludes the oncostatin M-mediated activation of a protein kinase A
      dependent transport route to the apical surface, which exits the subapical
      compartment (SAC). This transport route has previously been shown to be crucial
      for apical plasma membrane biogenesis. Together, our data indicate that
      oncostatin M-stimulated apicalization of the cell surface is critically dependent
      on the ability of oncostatin M to control p27(Kip1)/cdk2-mediated G(1)-S-phase
      progression and suggest that the regulation of apical plasma membrane-directed
      traffic from SAC is coupled to centrosome-associated signaling pathways.

PMID- 15240819
TI  - The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and
      mediates receptor down-regulation.
AB  - The biogenesis of multivesicular bodies and endosomal sorting of membrane cargo
      are driven forward by the endosomal sorting complexes required for transport,
      ESCRT-I, -II, and -III. ESCRT-I is characterized in yeast as a complex consisting
      of Vps23, Vps28, and Vps37. Whereas mammalian homologues of Vps23 and Vps28
      (named Tsg101 and hVps28, respectively) have been identified and characterized, a
      mammalian counterpart of Vps37 has not yet been identified. Here, we show that a
      regulator of proliferation, hepatocellular carcinoma related protein 1 (HCRP1),
      interacts with Tsg101, hVps28, and their upstream regulator Hrs. The ability of
      HCRP1 (which we assign the alternative name hVps37A) to interact with Tsg101 is
      conferred by its mod(r) domain and is shared with hVps37B and hVps37C, two other
      mod(r) domain-containing proteins. HCRP1 cofractionates with Tsg101 and hVps28 by
      size exclusion chromatography and colocalizes with hVps28 on LAMP1-positive
      endosomes. Whereas depletion of Tsg101 by siRNA reduces cellular levels of both
      hVps28 and HCRP1, depletion of HCRP1 has no effect on Tsg101 or hVps28.
      Nevertheless, HCRP1 depletion strongly retards epidermal growth factor (EGF)
      receptor degradation. Together, these results indicate that HCRP1 is a subunit of
      mammalian ESCRT-I and that its function is essential for lysosomal sorting of EGF
      receptors.

PMID- 15240820
TI  - Nutritional homeostasis in batch and steady-state culture of yeast.
AB  - We studied the physiological response to limitation by diverse nutrients in batch
      and steady-state (chemostat) cultures of S. cerevisiae. We found that the global
      pattern of transcription in steady-state cultures in limiting phosphate or
      sulfate is essentially identical to that of batch cultures growing in the same
      medium just before the limiting nutrient is completely exhausted. The massive
      stress response and complete arrest of the cell cycle that occurs when nutrients
      are fully exhausted in batch cultures is not observed in the chemostat,
      indicating that the cells in the chemostat are "poor, not starving." Similar
      comparisons using leucine or uracil auxotrophs limited on leucine or uracil again
      showed patterns of gene expression in steady-state closely resembling those of
      corresponding batch cultures just before they exhaust the nutrient. Although
      there is also a strong stress response in the auxotrophic batch cultures, cell
      cycle arrest, if it occurs at all, is much less uniform. Many of the differences
      among the patterns of gene expression between the four nutrient limitations are
      interpretable in light of known involvement of the genes in stress responses or
      in the regulation or execution of particular metabolic pathways appropriate to
      the limiting nutrient. We conclude that cells adjust their growth rate to
      nutrient availability and maintain homeostasis in the same way in batch and
      steady state conditions; cells in steady-state cultures are in a physiological
      condition normally encountered in batch cultures.

PMID- 15240821
TI  - Myofibroblast development is characterized by specific cell-cell adherens
      junctions.
AB  - Myofibroblasts of wound granulation tissue, in contrast to dermal fibroblasts,
      join stress fibers at sites of cadherin-type intercellular adherens junctions
      (AJs). However, the function of myofibroblast AJs, their molecular composition,
      and the mechanisms of their formation are largely unknown. We demonstrate that
      fibroblasts change cadherin expression from N-cadherin in early wounds to OB
      cadherin in contractile wounds, populated with alpha-smooth muscle actin (alpha
      SMA)-positive myofibroblasts. A similar shift occurs during myofibroblast
      differentiation in culture and seems to be responsible for the homotypic
      segregation of alpha-SMA-positive and -negative fibroblasts in suspension. AJs of
      plated myofibroblasts are reinforced by alpha-SMA-mediated contractile activity,
      resulting in high mechanical resistance as demonstrated by subjecting cell pairs
      to hydrodynamic forces in a flow chamber. A peptide that inhibits alpha-SMA
      mediated contractile force causes the reorganization of large stripe-like AJs to
      belt-like contacts as shown for enhanced green fluorescent protein-alpha-catenin
      transfected cells and is associated with a reduced mechanical resistance. Anti-OB
      cadherin but not anti-N-cadherin peptides reduce the contraction of myofibroblast
      populated collagen gels, suggesting that AJs are instrumental for myofibroblast
      contractile activity.

PMID- 15240822
TI  - Promoter-dependent roles for the Srb10 cyclin-dependent kinase and the Hda1
      deacetylase in Tup1-mediated repression in Saccharomyces cerevisiae.
AB  - The Tup1-Ssn6 complex has been well characterized as a Saccharomyces cerevisiae
      general transcriptional repressor with functionally conserved homologues in
      metazoans. These homologues are essential for cell differentiation and many other
      developmental processes. The mechanism of repression of all of these proteins
      remains poorly understood. Srb10 (a cyclin-dependent kinase associated with the
      Mediator complex) and Hda1 (a class I histone deacetylase) have each been
      implicated in Tup1-mediated repression. We present a statistically based genome
      wide analysis that reveals that Hda1 partially represses roughly 30% of Tup1
      repressed genes, whereas Srb10 kinase activity contributes to the repression of
      approximately 15% of Tup1-repressed genes. These effects only partially overlap,
      suggesting that different Tup1-repression mechanisms predominate at different
      promoters. We also demonstrate a distinction between histone deacetylation and
      transcriptional repression. In an HDA1 deletion, many Tup1-repressed genes are
      hyperacetylated at lysine 18 of histone H3, yet are not derepressed, indicating
      deacetylation alone is not sufficient to repress most Tup1-controlled genes. In a
      strain lacking both Srb10 and Hda1 functions, more than half of the Tup1
      repressed genes are still repressed, suggesting that Tup1-mediated repression
      occurs by multiple, partially overlapping mechanisms, at least one of which is
      unknown.

PMID- 15240823
TI  - A facile method for high-throughput co-expression of protein pairs.
AB  - We developed a method to co-express protein pairs from collections of otherwise
      identical Escherichia coli plasmids expressing different ORFs by incorporating a
      61-nucleotide sequence (LINK) into the plasmid to allow generation of tandem
      plasmids. Tandem plasmids are formed in a ligation-independent manner, propagate
      efficiently, and produce protein pairs in high quantities. This greatly
      facilitates co-expression for structural genomics projects that produce thousands
      of clones bearing identical origins and antibiotic markers.

PMID- 15240824
TI  - N-butyryl glucosamine increases matrix gene expression by chondrocytes.
AB  - Proteoglycan synthesis is dependent on N-acetyl glucosamine (GlcNAc) produced by
      the hexosamine biosynthetic pathway or obtained exogenously. Although used
      therapeutically to relieve symptoms of osteoarthritis, the actions of glucosamine
      and its analogs on cartilage are poorly understood. The purpose of this study was
      to determine the effects on chondrocytes of N-acylated-glucosamine analogs
      bearing alkyl chains of different lengths. Chondrocytes isolated from neonatal
      rat femoral condyles were cultured in the presence of glucosamine analogs.
      GlcNAc, N-proprionyl glucosamine (GlcNPro), or N-butyryl glucosamine (GlcNBu) did
      not alter cell number, lactate dehydrogenase release, or metabolic acid
      production, consistent with lack of cytotoxicity. Treatment of chondrocyte
      cultures with GlcNBu for 6 days significantly increased levels of type II
      collagen and aggrecan mRNA as determined by Northern blot analysis. In contrast,
      GlcNAc and GlcNPro had no significant effect. A significant increase in type II
      collagen mRNA was induced by GlcNBu within 3 days. GlcNBu did not alter stability
      of type II collagen mRNA, suggesting it acts on gene transcription. We have
      previously shown that tumor necrosis factor-alpha (TNFalpha) decreases levels of
      type II collagen mRNA. However, chondrocytes pretreated with GlcNBu maintained
      type II collagen mRNA at control levels in the presence of TNFalpha. These
      results establish that the N-butyrylated analog of glucosamine but not GlcNAc
      promotes matrix gene expression by chondrocytes. Thus, GlcNBu has the potential
      for use as a chondro-protective agent in osteoarthritis.

PMID- 15240825
TI  - Role of protein kinase Cdelta in endothelin-induced type I collagen expression in
      cardiac myofibroblasts isolated from the site of myocardial infarction.
AB  - The role of endothelin-1 (ET) in tissue remodeling/fibrogenesis has been
      demonstrated in various in vitro and in vivo models. Our previous studies have
      revealed ET-induced expression of type I collagen in cardiac myofibroblasts
      (myoFb). Here we report that protein kinase Cdelta (PKCdelta) and mitogen
      activated protein kinase/extracellular signal-regulated kinase-1/2 (MAPK/ERK1/2)
      play a role in ET-induced type I collagen expression using specific
      pharmacological inhibitors. The present study also reveals the expression of
      various isoforms of PKC including PKCalpha, PKCbetaI, PKCbetaII, PKCgamma,
      PKCdelta, PKCepsilon, PKCeta, and PKCzeta in cardiac myoFb. Our results from mRNA
      and protein studies demonstrate that calphostin-C, a PKC inhibitor, decreased the
      ET-induced type I collagen expression suggesting a role for the PKC pathway.
      Further treatment with rottlerin, a PKCdelta isoform-specific inhibitor,
      demonstrated attenuation of 80 to 90% of type I collagen expression induced by
      ET. However, Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H
      indolo[2,3-a]pyrrolo [3,4-c]carbazole]], an inhibitor of Ca(2+)-dependent PKC
      isoforms (PKCalpha and PKCbetaI), showed little to no effect on ET-stimulated
      type I collagen expression. Furthermore, the MAPK inhibitor PD98059 (2'-amino-3'
      methoxyflavone) attenuated ET-dependent activation of p44/42 MAPK (pERK1/2) and
      also down-regulated type I collagen expression. Similarly, rottlerin inhibited
      the activation of p44/42 MAPK (pERK) implicating the involvement of PKC and
      MAPK/ERK1/2 in ET-induced type I collagen expression. Our protein/DNA array and
      reverse transcription-polymerase chain reaction results from ET-treated samples
      showed a significant increase in Sp1 expression. PD98059 and rottlerin decreased
      ET-induced Sp1 expression, suggesting a possible interaction of Sp1 with PKCdelta
      and MAPK in ET-induced type I collagen expression in cardiac myoFb.

PMID- 15240826
TI  - Endogenous D-serine is involved in induction of neuronal death by N-methyl-D
      aspartate and simulated ischemia in rat cerebrocortical slices.
AB  - Emerging evidence indicates that D-serine rather than glycine serves as an
      endogenous agonist at glycine site of the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptors, in several nervous tissues, including the developing
      cerebellum and the retina. Here, we examined whether endogenous D-serine plays a
      significant role in neuronal damage resulting from excitotoxic insults in the
      cerebral cortex, using rat brain slices maintained in a defined salt solution.
      Neuronal cell death induced by application of NMDA or by oxygen-glucose
      deprivation (simulated ischemia) was markedly suppressed by a competitive glycine
      site antagonist 2,7-dichlorokynurenic acid. Addition of glycine or D-serine did
      not augment neuronal damage by NMDA or simulated ischemia, indicating that
      sufficient amount of glycine site agonist(s) is supplied endogenously within the
      slices. Application of D-amino acid oxidase, an enzyme that degrades D-serine,
      markedly inhibited neuronal damage by NMDA and simulated ischemia, which was
      reversed by addition of excess D-serine or glycine. Sensitivity to the glycine
      site antagonist of NMDA- or ischemia-induced damage was not affected by the
      presence of a non-NMDA receptor antagonist, suggesting that kainate receptor
      stimulated D-serine release as demonstrated in primary cultured astrocytes does
      not contribute significantly to the extent of neuronal injury in these settings.
      The present results suggest that endogenous supply of D-serine as a glycine site
      agonist is important for neuronal injury involving NMDA receptor overactivation
      in the cerebral cortex.

PMID- 15240827
TI  - Drug discrimination in methamphetamine-trained monkeys: effects of monoamine
      transporter inhibitors.
AB  - The involvement of brain monoamine systems in the discriminative stimulus effects
      of methamphetamine (MA) was studied in squirrel monkeys by evaluating the effects
      of differentially selective monoamine uptake inhibitors alone and in combination.
      In monkeys discriminating i.m. injections of 0.3 mg/kg MA from saline,
      methamphetamine (0.01-0.3 mg/kg), and dopamine transporter (DAT) inhibitors,
      including 1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-(3-phenylpropyl)piperazine
      (GBR 12909; 1.0-17.8 mg/kg) and its analogs AM2502 (1.0-17.8 mg/kg), AM2506 (1.0
      30.0 mg/kg), AM2515 (1.0-17.8 mg/kg), and AM2517 (1.0-5.6 mg/kg), produced dose
      related increases in responding on the MA-associated lever and, at the highest
      doses, full substitution. The time course of MA-like effects was similar for
      equivalent (3.0 mg/kg) doses of GBR 12909 and its most potent analog, AM2517.
      Unlike the DAT blockers, the selective 5-hydroxytryptamine (serotonin) uptake
      inhibitor clomipramine (1.0-10.0 mg/kg) and the selective norepinepherine (NE)
      uptake inhibitor desipramine (1.0-10 mg/kg) produced responding primarily on the
      saline lever. The selective NE uptake inhibitor nisoxetine partially substituted
      at the highest dose tested (10.0 mg/kg). Pretreatment with GBR 12909 or AM2517
      enhanced the discriminative stimulus effects of MA, shifting the dose-effect
      curve leftward. The NE uptake inhibitors desipramine or nisoxetine also enhanced
      the discriminative stimulus effects of MA, whereas clomipramine only attenuated
      them. These results support the view that dopaminergic mechanisms play a
      prominent role in the discriminative stimulus effects of MA in monkeys, whereas
      involvement of serotonergic and noradrenergic systems may be limited to a
      modulatory role.

PMID- 15240828
TI  - Sequence-based prediction of protein domains.
AB  - Guessing the boundaries of structural domains has been an important and
      challenging problem in experimental and computational structural biology.
      Predictions were based on intuition, biochemical properties, statistics, sequence
      homology and other aspects of predicted protein structure. Here, we introduced
      CHOPnet, a de novo method that predicts structural domains in the absence of
      homology to known domains. Our method was based on neural networks and relied
      exclusively on information available for all proteins. Evaluating sustained
      performance through rigorous cross-validation on proteins of known structure, we
      correctly predicted the number of domains in 69% of all proteins. For 50% of the
      two-domain proteins the centre of the predicted boundary was closer than 20
      residues to the boundary assigned from three-dimensional (3D) structures; this
      was about eight percentage points better than predictions by 'equal split'. Our
      results appeared to compare favourably with those from previously published
      methods. CHOPnet may be useful to restrict the experimental testing of different
      fragments for structure determination in the context of structural genomics.

PMID- 15240829
TI  - Demarcating the gene-rich regions of the wheat genome.
AB  - By physically mapping 3025 loci including 252 phenotypically characterized genes
      and 17 quantitative trait loci (QTLs) relative to 334 deletion breakpoints, we
      localized the gene-containing fraction to 29% of the wheat genome present as 18
      major and 30 minor gene-rich regions (GRRs). The GRRs varied both in gene number
      and density. The five largest GRRs physically spanning <3% of the genome
      contained 26% of the wheat genes. Approximate size of the GRRs ranged from 3 to
      71 Mb. Recombination mainly occurred in the GRRs. Various GRRs varied as much as
      128-fold for gene density and 140-fold for recombination rates. Except for a
      general suppression in 25-40% of the chromosomal region around centromeres, no
      correlation of recombination was observed with the gene density, the size, or
      chromosomal location of GRRs. More than 30% of the wheat genes are in
      recombination-poor regions thus are inaccessible to map-based cloning.

PMID- 15240831
TI  - New strategy for the representation and the integration of biomolecular knowledge
      at a cellular scale.
AB  - The combination of sequencing and post-sequencing experimental approaches
      produces huge collections of data that are highly heterogeneous both in structure
      and in semantics. We propose a new strategy for the integration of such data.
      This strategy uses structured sets of sequences as a unified representation of
      biological information and defines a probabilistic measure of similarity between
      the sets. Sets can be composed of sequences that are known to have a biological
      relationship (e.g. proteins involved in a complex or a pathway) or that share
      similar values for a particular attribute (e.g. expression profile). We have
      developed a software, BlastSets, which implements this strategy. It exploits a
      database where the sets derived from diverse biological information can be
      deposited using a standard XML format. For a given query set, BlastSets returns
      target sets found in the database whose similarity to the query is statistically
      significant. The tool allowed us to automatically identify verified relationships
      between correlated expression profiles and biological pathways using publicly
      available data for Saccharomyces cerevisiae. It was also used to retrieve the
      members of a complex (ribosome) based on the mining of expression profiles. These
      first results validate the relevance of the strategy and demonstrate the
      promising potential of BlastSets.

PMID- 15240830
TI  - Transcriptional activation of the human prostatic acid phosphatase gene by NF
      kappaB via a novel hexanucleotide-binding site.
AB  - Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific
      differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine
      phosphatase and is involved in regulating androgen-promoted prostate cancer cell
      proliferation. Despite the fact that the promoter of the PAcP gene has been
      cloned, the transcriptional factors that regulate PAcP expression remain
      unidentified. This article describes our analyses of the promoter of the PAcP
      gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed
      that a 577 bp fragment (-1356/-779) represents the unique positive cis-active
      element in human prostate cancer cells but not in HeLa cervix carcinoma cells.
      Interestingly, the 577 bp fragment contains a non-consensus nuclear factor kappaB
      (NF-kappaB)-binding site that is required for NF-kappaB up-regulation in prostate
      cancer cells, while NF-kappaB failed to have the same effect in HeLa cells.
      Conversely, inhibition of the NF-kappaB pathway stopped p65 NF-kappaB activation
      of the p1356 promoter activity. Gel shift and mutation analyses determined that
      AGGTGT (-1254/-1249) is the core sequence for NF-kappaB-binding and activation.
      Biologically, tumor necrosis factor-alpha (TNF-alpha) activated endogenous PAcP
      expression in LNCaP human prostate cancer cells. The data collectively indicate
      that NF-kappaB up-regulates PAcP promoter activity via its binding to the AGGTGT
      motif, a novel binding sequence located inside the cis-active enhancer element in
      human prostate cancer cells.

PMID- 15240832
TI  - The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient
      induced responses in yeast.
AB  - Dcs1, the m7GpppX pyrophosphatase of Saccharomyces cerevisiae, has been reported
      to 'scavenge' capped 5' end fragments generated by 3'-->5' mRNA degradation. We
      now show that the absence of Dcs1, and the closely related Dcs2 protein,
      compromises cellular responses to glucose-deprivation stress as well as to step
      changes in glucose availability. Dcs1 and Dcs2 form homo- and heterodimers, with
      the heterodimer appearing as cells enter diauxie. Despite the previously observed
      increase in abundance of the mRNA encoding the neutral trehalase (Nth1) in the
      stationary phase, the total enzyme activity of Nth1 decreases in this phase of
      growth. Changes in trehalase activity are significant because the non-reducing
      disaccharide trehalose is thought to stabilize cellular components under stress
      conditions. In the dcs1Delta and dcs1Deltadcs2Delta mutants, normal regulation of
      trehalase activity is lost. Nutrient stress induces DCS1 and DCS2 transcription
      via the cAMP-PKA signalling pathway. Dcs1 also becomes phosphorylated as the
      availability of glucose diminishes, and we test the role of this phosphorylation
      in the stress response. Further evidence indicates that Dcs1 plays a
      complementary role to the translation factor eIF4E in preventing capped 5'
      fragments of mRNA from interfering with translation initiation. We conclude that
      Dcs1 function influences cellular responses to changes in nutrient avialability,
      while Dcs2 seems to act as a modulator of Dcs1 function.

PMID- 15240833
TI  - Sequence-dependent nucleotide dynamics revealed by intercalated ring rotation in
      DNA-bisnaphthalimide complexes.
AB  - Bisnaphthalimide intercalators are anti-tumour agents composed of two planar
      rings linked by a flexible diazanonylene chain. The intercalated rings of three
      bisnaphthalimide analogues complexed to DNA are found here to undergo 180 degrees
      rotating motions that do not affect the diazanonylene linker atoms bound to the
      major groove. These ring rotations are detected by NMR spectroscopy in a broad
      range of sequence contexts and duplex lengths. A comparative analysis of the
      frequency and activation energies of such excited states in different complexes
      and conditions indicates that these motions (i) are unrelated to drug
      dissociation; (ii) are a consequence of concerted, sequence-dependent nucleotide
      movements taking place on the millisecond time scale; and (iii) may occur inside
      the DNA duplexes. The rotation frequencies range from 2 to 25 s(-1) at 25 degrees
      C, depending on DNA composition and the size of the rotating rings. The detected
      nucleotide dynamics are likely to play an important role in the binding kinetics
      of the numerous proteins and drugs that require base unstacking when interacting
      with DNA.

PMID- 15240834
TI  - Rapid evolution of RNA editing sites in a small non-essential plastid gene.
AB  - Chloroplast RNA editing proceeds by C-to-U transitions at highly specific sites.
      Here, we provide a phylogenetic analysis of RNA editing in a small plastid gene,
      petL, encoding subunit VI of the cytochrome b6f complex. Analyzing
      representatives from most major groups of seed plants, we find an unexpectedly
      high frequency and dynamics of RNA editing. High-frequency editing has previously
      been observed in plastid ndh genes, which are remarkable in that their mutational
      inactivation does not produce an obvious mutant phenotype. In order to test the
      idea that reduced functional constraints allow for more flexible evolution of RNA
      editing sites, we have created petL knockout plants by tobacco chloroplast
      transformation. We find that, in the higher plant tobacco, targeted inactivation
      of petL does not impair plant growth under a variety of conditions markedly
      contrasting the important role of petL in photosynthesis in the green alga
      Chlamydomonas reinhardtii. Together with a low number of editing sites in plastid
      genes that are essential to gene expression and photosynthetic activity, these
      data suggest that RNA editing sites may evolve more readily in those genes whose
      transitory loss of function can be tolerated. Accumulated evidence for this
      'relative neutrality hypothesis for the evolution of plastid editing sites' is
      discussed.

PMID- 15240835
TI  - Reverse Sanger sequencing of RNA by MALDI-TOF mass spectrometry after solid phase
      purification.
AB  - Several DNA/RNA sequencing strategies have been developed using matrix-assisted
      laser desorption ionization mass spectrometry (MALDI-MS). In the reverse Sanger
      sequencing approach alpha-thiophosphate-containing NTPs are employed. Sequencing
      ladders are produced by the subsequent exonuclease cleavage, which is inhibited
      by the alpha-S-NTP at the 3' terminus. Here the reverse Sanger sequencing of RNA
      is described. The stability of RNA during the UV-MALDI process is higher relative
      to DNA, and RNA can be easily synthesized by transcription using bacteriophage
      RNA polymerase. alpha-S-rNTP was added to the reaction in a ratio of 1:3 to the
      native rNTPs and was incorporated statistically by the RNA polymerase. Four
      separate sequence ladders were produced, to avoid the problem of the only 1u mass
      difference between uridine and cytidine. However, it was shown that RNA
      transcription does not produce homogeneous transcripts. Therefore isolation of
      the full-length transcript is required to attain a non-ambiguous interpretation
      of cleavage spectra. This is achieved by the exclusive immobilization of the full
      length transcript on a solid phase. The full-length transcripts were hybridized
      to magnetic beads, coated with short universal sequences, complementary to the in
      vitro RNA. After purification and isolation the RNA full-length transcript is
      cleaved by snake venom phosphodiesterase (SVP) and the obtained sequence ladder
      is analyzed by MALDI-MS.

PMID- 15240836
TI  - A simple, rapid, high-fidelity and cost-effective PCR-based two-step DNA
      synthesis method for long gene sequences.
AB  - Chemical synthesis of DNA sequences provides a powerful tool for modifying genes
      and for studying gene function, structure and expression. Here, we report a
      simple, high-fidelity and cost-effective PCR-based two-step DNA synthesis (PTDS)
      method for synthesis of long segments of DNA. The method involves two steps. (i)
      Synthesis of individual fragments of the DNA of interest: ten to twelve 60mer
      oligonucleotides with 20 bp overlap are mixed and a PCR reaction is carried out
      with high-fidelity DNA polymerase Pfu to produce DNA fragments that are
      approximately 500 bp in length. (ii) Synthesis of the entire sequence of the DNA
      of interest: five to ten PCR products from the first step are combined and used
      as the template for a second PCR reaction using high-fidelity DNA polymerase
      pyrobest, with the two outermost oligonucleotides as primers. Compared with the
      previously published methods, the PTDS method is rapid (5-7 days) and suitable
      for synthesizing long segments of DNA (5-6 kb) with high G + C contents,
      repetitive sequences or complex secondary structures. Thus, the PTDS method
      provides an alternative tool for synthesizing and assembling long genes with
      complex structures. Using the newly developed PTDS method, we have successfully
      obtained several genes of interest with sizes ranging from 1.0 to 5.4 kb.

PMID- 15240837
TI  - Successful lateral transfer requires codon usage compatibility between foreign
      genes and recipient genomes.
AB  - We present evidence supporting the notion that codon usage (CU) compatibility
      between foreign genes and recipient genomes is an important prerequisite to
      assess the selective advantage of imported functions, and therefore to increase
      the fixation probability of horizontal gene transfer (HGT) events. This contrasts
      with the current tendency in research to predict recent HGTs in prokaryotes by
      assuming that acquired genes generally display poor CU. By looking at the CU
      level (poor, typical, or rich) exhibited by putative xenologs still resembling
      their original CU, we found that most alien genes predominantly present typical
      CU immediately upon introgression, thereby suggesting that the role of CU
      amelioration in HGT has been overemphasized. In our strategy, we first scanned a
      representative set of 103 complete prokaryotic genomes for all pairs of candidate
      xenologs (exported/imported genes) displaying similar CU. We applied additional
      filtering criteria, including phylogenetic validations, to enhance the
      reliability of our predictions. Our approach makes no assumptions about the CU of
      foreign genes being typical or atypical within the recipient genome, thus
      providing a novel unbiased framework to study the evolutionary dynamics of HGT.

PMID- 15240838
TI  - Chloroplast phylogeny indicates that bryophytes are monophyletic.
AB  - Opinions on the basal relationship of land plants vary considerably and no
      phylogenetic tree with significant statistical support has been obtained. Here,
      we report phylogenetic analyses using 51 genes from the entire chloroplast genome
      sequences of 20 representative green plant species. The analyses, using
      translated amino acid sequences, indicated that extant bryophytes (mosses,
      liverworts, and hornworts) form a monophyletic group with high statistical
      confidence and that extant bryophytes are likely sisters to extant vascular
      plants, although the support for monophyletic vascular plants was not strong.
      Analyses at the nucleotide level could not resolve the basal relationship with
      statistical confidence. Bryophyte monophyly inferred using amino acid sequences
      has a good statistical foundation and is not rejected statistically by other data
      sets. We propose bryophyte monophyly as the currently best hypothesis.

PMID- 15240839
TI  - Molecular and mechanical characterization of aciniform silk: uniformity of
      iterated sequence modules in a novel member of the spider silk fibroin gene
      family.
AB  - Araneoid spiders use specialized abdominal glands to produce up to seven
      different protein-based silks/glues that have diverse physical properties. The
      fibroin sequences that encode aciniform fibers (wrapping silk) and the mechanical
      properties of these fibers have not been characterized previously. To gain a
      better understanding of the molecular radiation of spider silk fibroin genes,
      cDNA libraries derived from aciniform glands of the banded garden spider, Argiope
      trifasciata, were constructed, and unique silk transcripts were sequenced. There
      was evidence for a single silk fibroin gene that was expressed in the aciniform
      glands, and the inferred amino acid composition of the novel fibroin closely
      matched the amino acid contents of these glands. The inferred protein, aciniform
      spidroin 1 (AcSp1), is composed of highly homogenized repeats that are 200 amino
      acids in length. The long stretches of poly-alanine and glycine-alanine
      subrepeats, which are thought to account for the crystalline regions of minor
      ampullate and major ampullate fibers, are very poorly represented in AcSp1. The
      AcSp1 repeat unit is iterated minimally 14 times and does not display substantial
      sequence similarity to any previously described genes or proteins. Database
      searches, however, showed that the nonrepetitive carboxy-terminus contains
      stretches of matches to known spider fibroin sequences, suggesting that the AcSp1
      gene is a highly divergent member of the spider silk gene family. In phylogenetic
      analyses of carboxy-terminal sequences from araneid spiders, the aciniform
      sequence did not group strongly with clusters of fibroins from the flagelliform,
      minor ampullate, or major ampullate silk glands. Comparisons of stress/strain
      curves for major ampullate, minor ampullate, and aciniform silks from Argiope
      trifasciata showed significant differences in ultimate strength, extensibility,
      and toughness. Remarkably, the toughness of aciniform silk was 50% greater than
      the highest values typically recorded for major ampullate silk. These differences
      in performance, in combination with the radical divergence at the sequence level
      among fibroin paralogs, suggest a possible linkage between silk fibroin sequences
      and performance that should be explored in future structural/functional studies
      of aciniform silk.

PMID- 15240840
TI  - The malaria parasite's chloroquine resistance transporter is a member of the
      drug/metabolite transporter superfamily.
AB  - The malaria parasite's chloroquine resistance transporter (CRT) is an integral
      membrane protein localized to the parasite's acidic digestive vacuole. The
      function of CRT is not known and the protein was originally described as a
      transporter simply because it possesses 10 transmembrane domains. In wild-type
      (chloroquine-sensitive) parasites, chloroquine accumulates to high concentrations
      within the digestive vacuole and it is through interactions in this compartment
      that it exerts its antimalarial effect. Mutations in CRT can cause a decreased
      intravacuolar concentration of chloroquine and thereby confer chloroquine
      resistance. However, the mechanism by which they do so is not understood. In this
      paper we present the results of a detailed bioinformatic analysis that reveals
      that CRT is a member of a previously undefined family of proteins, falling within
      the drug/metabolite transporter superfamily. Comparisons between CRT and other
      members of the superfamily provide insight into the possible role of the protein
      and into the significance of the mutations associated with the chloroquine
      resistance phenotype. The protein is predicted to function as a dimer and to be
      oriented with its termini in the parasite cytosol. The key chloroquine-resistance
      conferring mutation (K76T) is localized in a region of the protein implicated in
      substrate selectivity. The mutation is predicted to alter the selectivity of the
      protein such that it is able to transport the cationic (protonated) form of
      chloroquine down its steep concentration gradient, out of the acidic vacuole, and
      therefore away from its site of action.

PMID- 15240841
TI  - Heidelberg's first experiences in establishing a living-donation liver
      transplantation programme.
AB  - BACKGROUND: Since indications for liver transplantation (LTx) have increased and
      the shortage of brain dead transplant organs continues, an increase in deaths
      related to extended waiting periods can be documented. Living-related LTx (LRLTx)
      is a good alternative that can help compensate the shortness of organs for
      transplantation and can reduce waiting periods and deaths related to a long
      waiting list. We started a LRLTx programme at the transplantation centre,
      Department of Surgery at the University of Heidelberg to increase our
      transplantation activities. In this article we present our primary experiences
      and protocol. METHODS: From September 2002 to June 2003, three LRLTx were
      performed. Indications in recipients were hepatocellular carcinoma in two cases
      and liver cirrhoses due to hepatitis B in one patient. Two patients received the
      right liver (segments V-VIII) of their donors. One patient received the complete
      liver collected as a Domino LTx. All liver transplants were performed without the
      use of a venous bypass. RESULTS: The peri- and post-operative courses of our
      donors were without complications, except for an infected intraabdominal bilioma,
      which was drained interventionally. The donors were fully able to work after the
      operation. The coordinative and logistical work should not be underestimated.
      CONCLUSIONS: This therapy should only be offered and performed in centres with
      excellent expert knowledge in liver and transplantation surgery.

PMID- 15240842
TI  - Regulation of liver regeneration.
AB  - BACKGROUND: Hepatocyte regeneration proceeds along a sequence of distinctive
      phases and results in a precise reconstitution of the lost tissue mass. The
      molecular mechanisms regulating liver regeneration have recently been elucidated.
      METHODS: Important aspects of the regulatory steps of hepatocyte proliferation
      during regeneration are summarized. RESULTS: Hepatocytes normally remain in
      proliferative quiescence. Regeneration requires priming of hepatocytes to achieve
      competence for proliferation. This is the initiation phase, which is regulated by
      cytokines, including interleukin-6 and tumour necrosis factor-alpha. During the
      subsequent proliferation, the hepatocyte population is expanded (the expansion
      phase), it being chiefly regulated by hepatocyte growth factor and transforming
      growth factor-alpha. Upon sensing of the required cell mass, the proliferation
      response is terminated (termination phase) and is mainly mediated by transforming
      growth factor-beta and activins. These structured processes go in line with a
      remodelling response, resulting in the reconstruction of a vascularized liver
      lobule. CONCLUSIONS: Liver regeneration proceeds in a highly ordered fashion,
      critical steps being regulated by several molecular mechanisms acting in a
      characteristic timely sequence.

PMID- 15240843
TI  - Living-donor liver transplantation: evaluation of donor and recipient.
AB  - Living-donor liver transplantation (LDLT) in adults has been expanded after
      becoming the standard for children in many transplant centres. Advantages of LDLT
      include thorough donor screening, optimization of timing for transplantation and
      minimal cold ischaemia time. However, the risk of donor morbidity and mortality
      must be considered. The preoperative evaluation of the donor typically is
      performed in consecutive stages. Specific donor considerations in LDLT are
      thrombosis and embolism, hepatic mass and hepatic steatosis. After complete
      evaluation, only a small proportion of potential donors are satisfactory
      candidates. The evaluation protocol for LDLT recipients in most centres is not
      different from that of cadaveric transplantation. More experience and the
      development of specific selection and evaluation criteria will further increase
      the benefit for the recipient and decrease the risk of the donor.

PMID- 15240844
TI  - Living-donor liver transplantation--European experiences.
AB  - To overcome the problem of organ shortage in recent years, liver transplantation
      from a living donor has been established. From a surgical standpoint, split liver
      transplantation and living-donor liver transplantation (LRLTx) are very complex
      surgical procedures requiring meticulous surgical techniques. LRLTx was first
      developed and performed in Asia and the USA. In the beginning of the 1990s, LRLTx
      was introduced in Europe. In Europe, 46 of 118 registered transplant centres had
      already performed LRLTx in December 2001. Up to this time point, more than 800
      LRLTx were performed since 1991. Medical discussions in the field of LRLTx
      include the need for high quality procedures, simplifying donor evaluation,
      optimizing surgical techniques and immunosuppression, all of which are current
      problems. The perioperative morbidity of the donor including all minor
      complications is stated to be 10-25%. Biliary complications of 5-10% are the
      major portion. The results of LRLTx for paediatric and adult recipients are
      comparable. The perioperative complication rate is slightly higher in LRLTx than
      after cadaver transplantation. This can be explained by the complexity of the
      surgical intervention with technical complications and the limited experience so
      far. Other reasons that can be ascertained are extended indications with higher
      incidence of tumour recurrence and infectious complications in these recipients.
      In recent years, LRLTx has emerged as a clinically safe alternative to cadaver
      transplantation in many cases and has further extended the donor pool. LRLTx has
      been shown to be a good option for patients with liver disease in which a long
      waiting time is not permitted.

PMID- 15240845
TI  - Immunosuppression and modulation in liver transplantation.
AB  - Recent advances in immunosuppressive drug regimens have changed the outcome after
      liver transplantation significantly in the last two decades. However, chronic
      rejection and long-term graft survival remains a major problem. Side effects like
      drug-induced nephrotoxicity, hypertension, osteoporosis, hyperlipidaemia and
      neuropathy of some immunosuppressive agents play an essential role in long-term
      allograft and patient survival. This review outlines the current treatment of
      short- and long-term immunosuppression in liver transplanted patients, it
      summarizes the treatment of acute and chronic rejection, describes the
      complications and side effects of immunosuppressive therapy and points out the
      current use of immunosuppressive therapy in living-related liver transplantation.

PMID- 15240846
TI  - New aspects on reperfusion injury to liver--impact of organ harvest.
AB  - The aetiology of primary graft non-function and dysfunction is unknown but most
      likely involves Kupffer cell-dependent reperfusion injury; however, reasons for
      transplant failure are complex and involve organ retrieval, preservation and
      transplantation. Important factors include the donor's condition, cold and warm
      ischaemic times, operative complications in the recipient, the immune status of
      the recipient and surgical experience. The donor operation and surgical technique
      also have an effect on outcome after transplantation. This is important, since
      surgical organ manipulation of the liver during harvest cannot be prevented
      completely with standard procedures. This is especially true during organ harvest
      for living-donor liver transplantation and split-liver transplantation in
      general. Most recently, an experimental setting has conclusively demonstrated
      that gentle in situ organ manipulation by touching, retracting and moving liver
      lobes gently during harvest dramatically reduces survival after transplantation
      via Kupffer cell-dependent mechanisms. These mechanisms involve disturbances of
      hepatic microcirculation, a hypermetabolic state of the liver, hypoxia and almost
      complete denudation of endothelial lining cells. Glycine, a non-essential, non
      toxic amino acid, which prevents activation of Kupffer cells, prevented all
      effects of harvest-related injury to the liver when given before transplantation.
      Based on these data, intravenous glycine has been administered to patients before
      reperfusion of their liver transplant. Both serum transaminases and the rate of
      primary non-function have been dramatically reduced, compared with historic
      controls. These preliminary clinical results with glycine before reperfusion are
      promising for further improvement of the overall outcome after liver
      transplantation.

PMID- 15240847
TI  - Laparoscopic living-donor nephrectomy.
AB  - BACKGROUND: In order to increase the number of renal donors, laparoscopic live
      donor nephrectomy (LLDN) was first performed 8 years ago. Today, LLDN is a
      routine procedure in many centres worldwide. We reviewed the literature with
      regard to extend the use of this method, the feasibility and safety for donor,
      graft and recipient. Laparoscopic and open-donor nephrectomy are compared, and
      the impact of LLDN on donors' willingness is evaluated. METHODS: Literature
      search (PubMed, DIMDI, Medline) for the period from 1995 to 2003. RESULTS: More
      than 200 centres worldwide perform LLDN. It is a feasible and safe surgical
      procedure. For the donor, LLDN has numerous advantages, while graft and recipient
      outcome are the same as with the open approach. The learning curve on the way to
      performing this operation safely is long, and surgeons planning to integrate LLDN
      into their programme must be trained thoroughly. There are some indications that
      with LLDN the number of donors willing to donate a kidney can be increased.
      CONCLUSIONS: LLDN is widely used and will spread further. It is of the utmost
      importance to undergo thorough laparoscopic training in general urology prior to
      performing this procedure.

PMID- 15240848
TI  - Evaluation of the living kidney donor.
AB  - Living donor renal transplantation is the preferred treatment for end-stage renal
      failure as the risk-benefit ratio for the recipient usually very much favours
      this approach. However, the benefit for the donor is much harder to define and
      probably very small if pure medical criteria are considered. Nonetheless 'non
      medical' issues (mostly socio-psychological) may outweigh the small medical risk.
      The medical pre-transplant evaluation of the potential donor must identify
      absolute contraindications and abnormalities, which would increase the peri
      operative risk. Difficulties may arise, if during the process, minor
      abnormalities are detected that marginally increase the acute or especially the
      long-term risk or whose implications are not well defined. In this situation two
      options are available. If the transplant team assumes that donation per se is of
      no benefit for the donor, transplantation should not be performed. If, however,
      the supposed 'non-medical' benefit is large enough, this approach will be against
      the principle of 'doing no harm' because the individual is denied the possibility
      to help somebody and might suffer from the consequences. In these complicated
      cases the final decision should be with the potential donor after an intense
      discussion with everybody involved in the transplantation process. Such an
      approach, however, necessitates a post-donation follow-up programme to be
      offered.

PMID- 15240849
TI  - The long-term consequences of living-related or unrelated kidney donation.
AB  - Since the frequency of living-related and unrelated kidney donation has increased
      in the past decade, the risk of uninephrectomy should not be neglected. Major
      complications after kidney donation are rare. No serious problems like infection
      or bleeding are common with an overall perioperative complication rate of 14%.
      Risk of long-term mortality is lower compared to the expected mortality. Little
      decrease of glomerular filtration rate immediately after transplantation occurs
      with no further decline. Risk of end-stage renal failure in living donors is
      approximately 0.2-0.5%. Only a few patients develop proteinuria. After age
      adjustment, no increase of blood pressure is noted. The benefit of living kidney
      transplantation is superceding the potential risks. After careful work-up of the
      donor short- and long-term risks are minimal.

PMID- 15240850
TI  - Results of renal transplantation using kidneys harvested from living donors at
      the University of Heidelberg.
AB  - BACKGROUND: Although a majority of patients undergoing renal transplantation
      currently receive a cadaver kidney, living donors continue to be an important
      source of transplanted kidneys. Recipients of living donor kidneys demonstrate
      improved graft survival. To expand the pool of suitable organ donors an organ
      procurement programme of living donors has been developed over the past 35 years.
      We have reviewed our living donor nephrectomy experience over this period to
      analyse the donor and recipient peri- and postoperative morbidity and mortality
      rate. METHODS: We reviewed the operative complications and the long-term outcome
      of 219 living donated kidney transplantations before and after introduction of
      cyclosporine A. Donor and graft complications as well as recipient complications
      and survival rate were investigated. Additionally, the findings of 16
      laparoscopically operated living donors were compared to a group of 20 patients
      who underwent a conventional surgery. RESULTS: The overall recipient 3 and 5 year
      survival rates in the cyclosporine A era were 95 and 94%, respectively. Prior to
      the introduction of cyclosporine A, the overall recipient survival rates at 3 and
      5 years were 84 and 84%, respectively. The overall graft survival rates were 92
      and 85% for the cyclosporine A era compared to 68 and 60% before introduction of
      cyclosporine A, at 3 and 5 years, respectively. The patient and graft survival
      rate in the cyclosporine group were significantly higher than in the pre
      cyclosporine group (log-rank: P = 0.0107 and P = 0.0003, respectively). Donor
      complications included pain at the incision site (35%), mild hypertension (27%),
      proteinuria (19%), urinary tract infections (11%), pneumothorax (5%), blood
      transfusion (3.5%) and wound infection (3%), with no mortalities. Our results
      showed a longer duration of operation, and longer warm ischaemia and cold
      ischaemia times in laparoscopically operated living donors than those that were
      seen in the conventional approach. There was no statistically significant
      difference in complications between both techniques. However, the hospitalization
      days and usage of analgesic medication in laparoscopy donors were lower than in
      the conventional approach. CONCLUSIONS: Similar to previous studies the results
      of the present analysis confirm an increase in patient and graft survival rates
      in the cyclosporine era compared to before its usage. Living donor nephrectomy,
      done through a conventional or laparoscopic approach, remains a valuable source
      of kidneys for transplantation with low complication rates.

PMID- 15240851
TI  - Analysis of NFAT-regulated gene expression in vivo: a novel perspective for
      optimal individualized doses of calcineurin inhibitors.
AB  - BACKGROUND: With the introduction of cyclosporine A (CsA) long-term allograft
      function has been significantly improved. Problems regarding limited therapeutic
      margins and CsA toxicity remain unsolved. Up to now there are no reliable,
      practical markers to measure the biological activity of CsA in vivo. METHODS:
      Expression of nuclear factor of activated T lymphocytes (NFAT)-regulated genes in
      PMA/ionomycin-stimulated peripheral blood from stable renal-transplant (n = 25)
      recipients under CsA therapy were measured by quantitative real-time RT-PCR
      before and 2 h after drug intake. The relative expression of three NFAT-regulated
      genes was scored, averaged and presented as the multi-gene expression score
      ranging from 0 to 12 points. Gene expression data and CsA plasma levels were
      correlated. RESULTS: A reliable and precise method to measure functional
      consequences of calcineurin inhibition in the individual patient was established.
      The individual decline in NFAT-regulated gene expression and the total drug
      exposure were in close relation (rho = 0.602). CONCLUSION: Quantitative
      measurement of NFAT-regulated gene expression in CsA-treated patients represents
      a potent new approach to assess the biological effectiveness of CsA therapy and
      has the potential to enable individualized immunosuppressive regimens.

PMID- 15240852
TI  - Tapering immunosuppression in recipients of living donor kidney transplants.
AB  - We have previously suggested that the in vitro donor-specific cytotoxic T
      lymphocyte precursor (CTLp) assay can guide us to identify patients in which the
      immunosuppressive load can be tapered. In a clinical trial we had observed that a
      low (<10/10(6) PBMC) frequency of these CTLp was predictive for an uneventful
      rejection-free clinical course in patients that were converted from calcineurin
      inhibitors to mycophenolate mofetil or azathiopine. In the present prospective
      study in 81 stable kidney transplant recipients, already converted from
      calcineurin inhibitors, we measured CTLp frequencies and reduced the
      immunosuppressive load on a routine basis when CTLp were <10/10(6) PBMC. Donor
      specific cytotoxicity could not be measured in 50/81 patients, while their
      reactivity against third-party lymphocytes was not impaired. These 50 patients
      were tapered in their immunosuppression. Only in one patient, who had stopped all
      his medication, was a rejection episode diagnosed. We conclude that in patients
      with a low donor-specific CTLp frequency it is safe to reduce the
      immunosuppression.

PMID- 15240853
TI  - Do we need screening for thrombophilia prior to kidney transplantation?
AB  - BACKGROUND: There is increased risk for the occurrence of deep venous thrombosis
      (DVT) and renovascular thrombosis after kidney transplantation. A disruption of
      the blood homeostasis caused by surgery and leading to clotting and bleeding
      malfunctions is widely accepted. However, other causes such as inherited or
      acquired disorders of the clotting system may further increase the risk of
      thrombosis. Here, we summarize and review data on possible causes, incidence and
      ways to prevent the occurrence of DVT and/or renovascular thrombosis after kidney
      transplantation. RESULTS: The incidence of DVT after kidney transplantation is
      6.2-8.3% and approximately 25% of these patients suffer from pulmonary embolism.
      The DVT occurs primarily on the side of the transplant with an increased risk
      throughout the first 5 months after transplantation. Thereby, 2-12% of the
      patients develop renovascular thromboses, most of which are related directly to
      the surgery. However, inherited or acquired thrombophilia may also play an
      important role. A severe course is known for prothrombin gene G20210A
      polymorphism, which can result in graft loss. A great diversity of prophylactic
      treatments is available but adjustment to the underlying circumstances is crucial
      for a favourable outcome. Low-dose heparin prophylaxis for at least 2-3 weeks can
      be used as standard therapy to prevent the occurrence of DVT after kidney
      transplantation. However, this may not be sufficient for concurrent disorders of
      the blood homeostasis such as elevated levels of antiphospholipid antibodies,
      lupus anticoagulant, prothrombin gene G20210A polymorphism or a combined
      inherited thrombophilia. These patients may need a prophylactic anticoagulation
      with coumarins starting prior to transplantation and being continued for at least
      1 year or even lifelong. Only randomized trials can answer the question
      concerning optimal duration and safety of coumarins in this setting. CONCLUSIONS:
      DVT and/or renovascular thromboses are severe complications after kidney
      transplantation. Inherited and acquired thrombophilia, apart from surgery and
      abnormal anatomy itself, have to be considered and proper prophylactic treatment
      initiated.

PMID- 15240855
TI  - Donor-recipient interaction: the Heidelberg model of evaluation and consultation.
AB  - BACKGROUND: In order to avoid psychological complications in living-donor
      transplantation, careful evaluation and consultation of the donor-recipient
      system is necessary. This article describes the Heidelberg consultation procedure
      before and after transplantation. This approach emphasizes close collaboration
      between physician and psychologist in joint interviews. METHODS: Consultations
      focus on family genogram, the history of the donation idea; stability and balance
      of relationship; expectations; hesitations and doubts; discussion of
      complications; previous hospital experiences; the offer to provide crisis
      intervention when needed. RESULTS: In 20% of all cases, unresolved problems
      appear. These include: unilaterally dependent relationships; unrealistic hopes
      for change; anxious avoidance to reflect complications; lack of medical
      information; risky health behaviour; negative experiences with hospitals. When
      properly consulted, half of these couples resign from transplantation.
      CONCLUSIONS: Close physician-psychologist collaboration adds significant value to
      a 'psychologist-only' consultation. Discussing hesitations and concerns
      strengthens confidence in the professional transplantation system. Access to post
      transplant consultation needs further improvement.

PMID- 15240854
TI  - Long-term results of paediatric kidney transplantation at the University of
      Heidelberg: a 35 year single-centre experience.
AB  - BACKGROUND: Kidney transplantation remains the most effective treatment for
      children with end-stage renal disease. We analysed data from the University of
      Heidelberg transplant programme to present our results on paediatric kidney
      transplantations over the past 35 years. METHODS: From 1967 to 2003, 354
      paediatric kidney transplantations were performed at the University of
      Heidelberg. Data were obtained from the paediatric kidney transplantation records
      consisting of 291 (82%) cadaveric and 63 (18%) living donated transplants.
      Demographic data, family relationship of the living donors, surgical technique,
      immunosuppressive drugs, graft and patient survival rates were assessed. RESULTS:
      The mean age of cadaveric and living donors was 32.0+/-17.1 and 37.6+/-7.5 years,
      respectively. The family relationship of the living donors included the mother in
      65% of cases, the father in 31%, and other relatives in 4%. In the last 4 years,
      the respective mean cold ischaemia time was 1.6+/-0.5 h for living donated and
      13.5+/-4.1 h for cadaveric donors. The mean age of children who received kidneys
      from cadaveric and living donors was 11.3+/-4.5 and 10.4+/-4.5 years,
      respectively, with a male to female ratio of 57 to 43%. Overall patient survival
      rates were 95% after 1 year and 89% after 5 years. The patient 5 and 10 year
      survival rates for living donor renal transplantations were 95 and 95%,
      respectively. Graft survival rates improved since 1990 compared with the period
      prior to 1990: 82.5 vs 56.7% graft survival at 1 year and 82.5 vs 50% after 5
      years (P = 0.03). Comparing the operating technique in a subgroup of our patients
      that received the same immunosuppressive regimen, anastomoses with the aorta and
      vena cava (51%, n = 31) were associated with a graft survival of 86.6 and 83.3%
      after 1 and 5 years, whereas anastomoses with iliac vessels (49%, n = 30) were
      associated with a graft survival of 55.8 and 51.6% after 1 and 5 years,
      respectively (P = 0.01). CONCLUSIONS: There has been a gradual improvement in our
      paediatric kidney transplantation results over time. Living donor paediatric
      kidney transplants have higher patient and better graft survival rates than
      cadaveric donor kidney transplants. Using the aorta and inferior vena cava for
      graft anastomosis, utilizing newer immunosuppressive drugs and implementing
      living kidney donation have positively affected the results of our paediatric
      kidney transplantations.

PMID- 15240856
TI  - Noninvasive assessment of fetal pulmonary blood flow in experimental pulmonary
      hypertension in the fetal lamb.
AB  - The aim of this study was to assess pulmonary arterial blood flow changes induced
      by the creation of a systemic arteriovenous fistula (120 d gestation) in the
      fetal lamb using Doppler technique. Doppler echocardiographic assessment of the
      pulmonary artery blood flow performed 1, 6, and 14 d after surgery showed that
      mean pulmonary arterial blood flow in the left or right pulmonary artery was 224
      +/- 58 mL/min at day 1 in the fistula group, significantly higher than in the
      control group (113 +/- 22 mL/min; p < 0.01, ANOVA test) whether no difference was
      found at days 6 and 14. The mean inner diameter of the left pulmonary artery
      measured on postmortem lung arteriograms compared favorably to the one measured
      on day 14 at the same level on ultrasound. The mean left pulmonary arterial blood
      flow, measured at birth on day 14 after surgery, using ultrasonic flow
      transducer, was not statistically different from the one measured by Doppler on
      day 14. Our data demonstrate that echocardiography allows accurate assessment of
      pulmonary arterial blood flow in utero, providing evidence suggesting transient
      high pulmonary blood flow that did not last >6 d after the creation of a systemic
      fistula.

PMID- 15240857
TI  - Sudden infant death syndrome: case-control frequency differences at genes
      pertinent to early autonomic nervous system embryologic development.
AB  - We have previously identified polymorphisms in the serotonin transporter gene
      promoter region and in intron 2 that were more common among sudden infant death
      syndrome (SIDS) cases compared with control subjects. To elucidate further the
      genetic profile that might increase an infant's vulnerability to SIDS, we focused
      on the recognized relationship between autonomic nervous system (ANS)
      dysregulation and SIDS. We therefore studied genes pertinent to early embryologic
      development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1,
      TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched
      control subjects. Eleven protein-changing rare mutations were identified in 14 of
      92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these
      mutations (TLX3) was identified in 2 of 92 control subjects. Black infants
      accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four
      protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and
      EDN1, but the allele frequency did not differ between SIDS cases and control
      subjects. However, among SIDS cases, the allele frequency for the BMP2 common
      polymorphism demonstrated ethnic differences; among control subjects, the allele
      frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic
      differences. These data represent further refinement of the genetic profile that
      might place an infant at risk for SIDS.

PMID- 15240858
TI  - Hepatitis B: the next generation.

PMID- 15240859
TI  - Longitudinal study on mutation profiles of core promoter and precore regions of
      the hepatitis B virus genome in children.
AB  - Precore nucleotide 1896 and core promoter mutations may account for hepatitis B e
      antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, yet
      the mutational profiles of the core promoter are largely unknown in children. An
      age-matched, case-control study enrolled 110 chronic HBV-infected children,
      including 55 HBeAg seroconverters and 55 nonseroconverters. Precore and core
      promoter genes of HBV were sequenced and the serum viral genomes were genotyped
      from three serial serum samples of the seroconverters and from one serum sample
      of the nonseroconverters. Higher frequency of A1775G and G1799C mutation rates
      and lower frequency of A1752G mutation rate were found in the seroconverters.
      Precore 1896 mutation appeared more in seroconverters than in nonseroconverters
      (45.5% versus 10.9%; p < 0.001). 1762 + 1764 mutation rates were not different
      between the seroconverters (9.1%) and the nonseroconverters (5.5%). Genotype B
      was the major type. Genotype C was associated with core promoter 1762 + 1764
      mutations in the seroconverter group (p = 0.023). The conclusions of this study
      include the following: 1) mutations of core promoter at nucleotide position 1752,
      1775, and 1799 have significant correlations with HBeAg seroconversion; 2) core
      promoter 1762 + 1764 mutations play a minimal role in HBeAg seroconversion; 3)
      precore 1896 mutant accounted for half of childhood HBeAg seroconversion; 4)
      genotype C is associated with 1762 + 1764 mutations during the process of HBeAg
      seroconversion.

PMID- 15240860
TI  - Stress during pregnancy affects general intellectual and language functioning in
      human toddlers.
AB  - Prenatal maternal stress has been shown to impair functioning in nonhuman primate
      offspring. Little is known about the effects of prenatal stress on intellectual
      and language development in humans because it is difficult to identify
      sufficiently large samples of pregnant women who have been exposed to an
      independent stressor. We took advantage of a natural disaster (January 1998 ice
      storm in Quebec, Canada) to determine the effect of the objective severity of
      pregnant women's stress exposure on general intellectual and language development
      of their children. Bayley Mental Development Index (MDI) scores and parent
      reported language abilities of 58 toddlers of mothers who were exposed to varying
      levels of prenatal stress were obtained at 2 y of age. The hierarchical multiple
      regression analyses indicated that the toddlers' birth weight and age at testing
      accounted for 12.0% and 14.8% of the variance in the Bayley MDI scores and in
      productive language abilities, respectively. More importantly, the level of
      prenatal stress exposure accounted for an additional 11.4% and 12.1% of the
      variance in the toddlers' Bayley MDI and productive language abilities and
      uniquely accounted for 17.3% of the variance of their receptive language
      abilities. The more severe the level of prenatal stress exposure, the poorer the
      toddlers' abilities. The level of prenatal stress exposure accounted for a
      significant proportion of the variance in the three dependent variables above and
      beyond that already accounted for by non-ice storm-related factors. We suspect
      that high levels of prenatal stress exposure, particularly early in the
      pregnancy, may negatively affect the brain development of the fetus, reflected in
      the lower general intellectual and language abilities in the toddlers.

PMID- 15240861
TI  - Platelet serotonin in newborns and infants: ontogeny, heritability, and effect of
      in utero exposure to selective serotonin reuptake inhibitors.
AB  - Ontogeny of platelet serotonin (5-hydroxytryptamine, 5-HT) during the first year
      of life was examined in newborns and infants. The effects of in utero exposure to
      selective serotonin reuptake inhibitors (SSRI, including fluoxetine, sertraline,
      and citalopram) were examined by comparing cord blood 5-HT levels in exposed and
      unexposed newborns. Heritability was assessed by correlation of the platelet 5-HT
      values observed for mother-infant pairs. No age effect was observed in 1-49 wk
      old infants (r = 0.13, p = 0.49) and mean platelet 5-HT levels in infants (241 +/
      102 ng/mL, n = 33; 615 +/- 320 ng/10(9) platelets, n = 32) were similar to those
      reported for older children and adults. However, significantly lower blood 5-HT
      levels were observed in newborns (81.3 +/- 32.5 ng/mL, n = 16, p < 0.0001; 297 +/
      101 ng/10(9) platelets, n = 11, p = 0.0007) compared with the 1-49 wk-old
      infants. The mean cord blood 5-HT concentrations in newborns exposed in utero to
      SSRI (n = 8) were substantially lower than that seen in unexposed (n = 16)
      newborns (20.6 +/- 14.4 versus. 81.3 +/- 32.5 ng/mL, p = 0.0001; 90.7 +/- 55.4
      versus. 297 +/- 101 ng/10(9) platelets, p = 0.0005). Platelet serotonin levels
      (ng/10(9) platelets) in mother-child pairs (n = 32) were significantly correlated
      (r = 0.415, p = 0.018). The results indicate that, although platelet 5-HT is low
      at birth, values quickly increase and stabilize at near-adult levels by 1 mo of
      age. Gestational exposure to SSRI appears to substantially reduce platelet 5-HT
      uptake in the fetus, strongly suggesting that such exposure has important
      physiologic effects. The observed mother-infant correlation agrees with a
      previous report of high heritability in a large adult population.

PMID- 15240862
TI  - Metabolic responses to protein restriction during pregnancy in rat and
      translation initiation factors in the mother and fetus.
AB  - A low-protein diet during pregnancy in the rat results in intrauterine growth
      restricted (IUGR) fetuses. The adaptive responses of the mother to low-protein
      diet and the mechanisms of IUGR in this model are not understood. In the present
      study, we report the maternal metabolic responses to protein restriction and
      their impact on growth, carcass composition, and translation initiation in the
      fetus. Pregnant Sprague-Dawley rats were pair-fed either a 6% protein (LP, n = 7)
      or a 24% protein (NP, n = 7) diet from conception until delivery. Plasma amino
      acids and urea levels and rate of oxygen consumption were measured sequentially
      through pregnancy. Translation initiation factors eIF2alpha, Ser51 phosphorylated
      eIF2alpha, eIF4E, phosphorylated eIF4E, and 4E-BP1 were quantified in the
      maternal and fetal muscle and liver. Protein restriction resulted in higher rate
      of oxygen consumption (p < 0.01), lower plasma branched chain amino acid (p <
      0.05) in the mother, and lower plasma histidine levels (p < 0.05) in the fetus.
      Plasma urea nitrogen was lower in the LP group throughout gestation. The
      phosphorylated 4E-BP1 (gamma form) in the maternal liver was 4-fold higher in the
      LP group. The phosphorylated eIF2alpha was higher in the livers of IUGR fetuses.
      We speculate that the lower plasma branched chain amino acids in the mother
      during early pregnancy may be due to a lower rate of protein turnover in the LP
      group. The mechanism of increased energy consumption due to protein restriction
      remains unclear. The data on translation initiation factors suggest a higher rate
      of protein synthesis in the maternal liver and a lower rate in the fetal liver in
      response to protein restriction.

PMID- 15240863
TI  - Altered lung development after prenatal nicotine exposure in young lambs.
AB  - There is compelling evidence that prenatal nicotine exposure permanently alters
      lung development and airway function. The aim of this study was to determine how
      prenatal nicotine exposure alters proximal and distal airway function. Thirteen
      lambs were continuously exposed during the last fetal trimester to low-dose
      nicotine (LN) and 12 to a moderate dose (MN) (maternal s.c. dose: 0.5 and 1.5
      mg/kg/d, respectively). Ten lambs served as controls (C). Proximal airway
      function was measured by lung mechanics. A multiple-breath N2 washout technique
      was used to measure lung volume (functional residual capacity) and efficiency of
      gas mixing in distal airways, i.e. terminal respiratory units (moment ratio and
      nitrogen clearance). In comparison with C, both LN and MN had significantly
      reduced specific airway conductance to the same extent at a median study age of
      12, 25, and 51 d, indicating signs of proximal airway obstruction. Distal airway
      function showed significant improvement in LN. Ventilation and functional
      residual capacity were unaffected. In summary, prenatal nicotine exposure induced
      airway obstruction in proximal airways and improved gas mixing in distal airways,
      possibly reflecting restriction in proximal airway growth and accelerated
      maturation of the acinar part of the lung, respectively. We speculate that
      prenatal nicotine exposure has a disparate impact on airway development and
      function. The effect on the distal airways seemed to be inversely related to
      dose, which was not the case in the large airways. The altered airway function
      persisted during the study period, indicating that the effects of prenatal
      nicotine exposure might be permanent.

PMID- 15240864
TI  - A galactosylceramide binding domain is involved in trafficking of CLN3 from Golgi
      to rafts via recycling endosomes.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is due to mutations in the CLN3
      gene. We previously determined that CLN3 protein harbors a highly conserved
      motif, VYFAE, necessary for its impact on cell growth and apoptosis. Using
      molecular modeling we demonstrated that this motif is embedded in a stretch of
      amino acids that is homologous to and structurally compatible with a
      galactosylceramide (GalCer) binding domain. This domain is present in the V3 loop
      of the HIV-1 gp120 envelope protein, beta-amyloid protein, and the infectious
      form of prionic protein, and defines a binding site for lipid rafts. We
      determined the subcellular localization of CLN3 in different cell systems
      including human neurons, primary rat hippocampal neurons, normal human
      fibroblasts, and JNCL fibroblasts homozygous for the 1.02 kb deletion in genomic
      DNA. Wild-type CLN3 protein was present within Golgi, lipid rafts in the plasma
      membrane, and early recycling endosomes, but not late endosomes/lysosomes. Wild
      type CLN3 internalized from the plasma membrane to the Golgi via Rab4- and Rab11
      positive recycling endosomes. Wild-type CLN3 co-localized with GalCer in the
      Golgi and in lipid rafts at the plasma membrane in normal cells. Neither mutant
      CLN3 protein nor GalCer were found at the plasma membrane in JNCL fibroblasts.
      Mutant CLN3p was retained within the Golgi and partially mis-localized to
      lysosomes, failing to reach recycling endosomes, plasma membrane, or lipid rafts.
      These studies identify a novel CLN3 domain that may dictate localization and
      function of CLN3.

PMID- 15240865
TI  - Genes and Sudden Infant Death Syndrome.

PMID- 15240866
TI  - Developmental origins of disease paradigm: a mechanistic and evolutionary
      perspective.
AB  - Fetal growth is determined by the interaction between the environment and the
      fetal genome. The fetal environment, in turn, is determined by the maternal
      environment and by maternal and placental physiology. There is evidence that the
      interaction between the fetal environment and genome can determine the risk of
      postnatal disease, as well as the individual's capacity to cope with the
      postnatal environment. Furthermore, the role of various forms of maternal
      constraint of fetal growth in determining the persistence of these responses is
      reviewed. A limited number of biologic processes can contribute to the
      mechanistic basis of these phenomena. In addition to immediate homeostatic
      responses, the developing organism may make predictive adaptive responses of no
      immediate advantage but with long-term consequences. An evolutionary perspective
      is provided, as well as a review of possible biologic processes. The
      "developmental origins of disease" paradigm is a reflection of the persistence of
      such mechanisms in humans who now live in very different environments from those
      within which they evolved. The developmental origins paradigm and its underlying
      mechanistic and evolutionary basis have major implications for addressing the
      increasing burden of metabolic and cardiovascular disease.

PMID- 15240867
TI  - Oxygen tension and inhaled nitric oxide modulate pulmonary levels of S
      nitrosocysteine and 3-nitrotyrosine in rats.
AB  - The oxidative environment within the lung generated upon administration of oxygen
      may be a critical regulator for the efficacy of inhaled nitric oxide therapy,
      possibly as a consequence of changes in nitrosative and nitrative chemistry.
      Changes in S-nitrosocysteine and 3-nitrotyrosine adducts were therefore evaluated
      after exposure of rats to 80% or >95% oxygen for 24 or 48 h with and without 20
      ppm inhaled nitric oxide. Exposure to 80% oxygen led to increased formation of S
      nitrosocysteine and 3-nitrotyrosine adducts in lung tissue that were also
      associated with increased expression of iNOS. The addition of inhaled nitric
      oxide in 80% oxygen exposure did not alter any of these adducts in the lung or in
      the bronchoalveolar lavage (BAL). Exposure to >95% oxygen led to a significant
      decrease in S-nitrosocysteine and an increase in 3-nitrotyrosine adducts in the
      lung. Co-administration of inhaled nitric oxide with >95% oxygen prevented the
      decrease in S-nitrosocysteine levels. The levels of S-nitrosocysteine and 3
      nitrotyrosine returned to baseline in a time-dependent fashion after termination
      of exposure to >95% oxygen and inhaled nitric oxide. These data suggest the
      formation of S-nitrosating and tyrosine-nitrating species is regulated by oxygen
      tensions and co-administration of inhaled nitric oxide restores the nitrosative
      chemistry without a significant impact upon the nitrative pathway.

PMID- 15240868
TI  - Developmental expression of endothelin receptors in postnatal swine mesenteric
      artery.
AB  - Studies were conducted to determine whether endothelin (ET) ETA and ETB receptor
      protein and mRNA expression is developmentally regulated in the postnatal swine
      mesenteric circulation. To this end, Western blotting and real-time reverse PCR
      were performed on protein and total RNA isolated from the mesenteric artery
      harvested from 3-, 10-, and 30-d-old swine. Western blot analysis revealed that
      ETA and ETB receptor protein expression in the swine mesenteric artery decreased
      over the age range studied; thus, ETA and ETB receptor protein expression was
      significantly greater in the 3-d-old group then progressively declined over the
      first postnatal month. Similar to the Western data, real-time PCR analysis
      revealed that ETA and ETB receptor mRNA expression also decreased over the age
      range studied; thus, ETA and ETB receptor mRNA expression was significantly
      greater in the 3-d-old group then progressively declined over the first postnatal
      month. Immunohistochemistry localized the ETA receptor to the vascular smooth
      muscle and the ETB receptor to the endothelial cell layer. Additionally, we
      report a partial cDNA sequence for the swine ETB receptor. We conclude that ETA
      and ETB receptor protein and mRNA expression is developmentally regulated in the
      postnatal swine mesenteric artery, being expressed to a greater degree in younger
      animals.

PMID- 15240869
TI  - Carnitine content and expression of mitochondrial beta-oxidation enzymes in
      placentas of wild-type (OCTN2(+/+)) and OCTN2 Null (OCTN2(-/-)) Mice.
AB  - Placenta requires energy to support its rapid growth, maturation, and transport
      function. Fatty acids are used as energy substrates in placenta, but little is
      known about the role played by carnitine in this process. We have investigated
      the role of carnitine in the expression of the enzymes involved in fatty acid
      beta-oxidation in placenta of OCTN2(-/-) mice with defective carnitine
      transporter (OCTN2). Heterozygous (OCTN2(+/-)) female mice were mated with
      heterozygous (OCTN2(+/-)) male mice. Pregnant mice were killed and fetuses and
      placentas were collected. Carnitine was measured using HPLC and tandem mass
      spectrometry. Immunohistochemistry was used to detect enzyme expression. Enzyme
      activities were measured spectrophotometrically. The fetal and placental weights
      were similar among the three genotypes (OCTN2(+/+), OCTN2(+/-), and OCTN2(-/-)).
      The levels of carnitine were markedly reduced (<20%) in homozygous OCTN2(-/-)
      null fetuses and placentas compared with wild-type OCTN2(+/+) controls. However,
      carnitine concentration in placenta was 2- to 7-fold higher than in the fetus in
      all three genotypes. Immunohistochemistry revealed that beta-oxidation enzymes
      are expressed in trophoblast cells. Catalytic activities of these enzymes were
      present at comparable levels in wild-type (OCTN2(+/+)) and homozygous (OCTN2(-/
      )) mouse placentas, with the exception of SCHAD, for which activity was
      significantly higher in OCTN2(-/-) placentas than in OCTN2(+/+) placentas. These
      data show that placental OCTN2 is obligatory for accumulation of carnitine in
      placenta and fetus, that fatty acid beta-oxidation enzymes are expressed in
      placenta, and that reduced carnitine levels up-regulate the expression of SCHAD
      in placenta.

PMID- 15240871
TI  - Signature quantization and representations of compact Lie groups.
AB  - We discuss some applications of signature quantization to the representation
      theory of compact Lie groups. In particular, we prove signature analogues of the
      Kostant formula for weight multiplicities and the Steinberg formula for tensor
      product multiplicities. Using symmetric functions, we also find, for type A,
      analogues of the Weyl branching rule and the Gel'fand-Tsetlin theorem.

PMID- 15240870
TI  - Rapid recent growth and divergence of rice nuclear genomes.
AB  - By employing the nuclear DNA of the African rice Oryza glaberrima as a reference
      genome, the timing, natures, mechanisms, and specificities of recent sequence
      evolution in the indica and japonica subspecies of Oryza sativa were identified.
      The data indicate that the genome sizes of both indica and japonica have
      increased substantially, >2% and >6%, respectively, since their divergence from a
      common ancestor, mainly because of the amplification of LTR-retrotransposons.
      However, losses of all classes of DNA sequence through unequal homologous
      recombination and illegitimate recombination have attenuated the growth of the
      rice genome. Small deletions have been particularly frequent throughout the
      genome. In >1 Mb of orthologous regions that we analyzed, no cases of complete
      gene acquisition or loss from either indica or japonica were found, nor was any
      example of precise transposon excision detected. The sequences between genes were
      observed to have a very high rate of divergence, indicating a molecular clock for
      transposable elements that is at least 2-fold more rapid than synonymous base
      substitutions within genes. We found that regions prone to frequent insertions
      and deletions also exhibit higher levels of point mutation. These results
      indicate a highly dynamic rice genome with competing processes for the generation
      and removal of genetic variation.

PMID- 15240872
TI  - Mouse dyskerin mutations affect accumulation of telomerase RNA and small
      nucleolar RNA, telomerase activity, and ribosomal RNA processing.
AB  - Dyskerin is a nucleolar protein present in small nucleolar ribonucleoprotein
      particles that modify specific uridine residues of rRNA by converting them to
      pseudouridine. Dyskerin is also a component of the telomerase complex. Point
      mutations in the human gene encoding dyskerin cause the skin and bone marrow
      failure syndrome dyskeratosis congenita (DC). To test the extent to which
      disruption of pseudouridylation or telomerase activity may contribute to the
      pathogenesis of DC, we introduced two dyskerin mutations into murine embryonic
      stem cells. The A353V mutation is the most frequent mutation in patients with X
      linked DC, whereas the G402E mutation was identified in a single family. The
      A353V, but not the G402E, mutation led to severe destabilization of telomerase
      RNA, a reduction in telomerase activity, and a significant continuous loss of
      telomere length with increasing numbers of cell divisions during in vitro
      culture. Both mutations caused a defect in overall pseudouridylation and a small
      but detectable decrease in the rate of pre-rRNA processing. In addition, both
      mutant embryonic stem cell lines showed a decrease in the accumulation of a
      subset of H/ACA small nucleolar RNAs, correlating with a significant decrease in
      site-specific pseudouridylation efficiency. Interestingly, the H/ACA snoRNAs
      decreased in the G402E mutant cell line differed from those affected in A353V
      mutant cells. Hence, our findings show that point mutations in dyskerin may
      affect both the telomerase and pseudouridylation pathways and the extent to which
      these functions are altered can vary for different mutations.

PMID- 15240873
TI  - IL-1beta: an endosomal exit.

PMID- 15240874
TI  - A freestanding proofreading domain is required for protein synthesis quality
      control in Archaea.
AB  - Threonyl-tRNA synthetase (ThrRS) participates in protein synthesis quality
      control by selectively editing the misacylated species Ser-tRNA(Thr). In bacteria
      and eukaryotes the editing function of ThrRS resides in a highly conserved N
      terminal domain distant from the active site. Most archaeal ThrRS proteins are
      devoid of this editing domain, suggesting evolutionary divergence of quality
      control mechanisms. Here we show that archaeal editing of Ser-tRNAThr is
      catalyzed by a domain unrelated to, and absent from, bacterial and eukaryotic
      ThrRSs. Despite the lack of sequence homology, the archaeal and bacterial editing
      domains are both reliant on a pair of essential histidine residues suggestive of
      a common catalytic mechanism. Whereas the archaeal editing module is most
      commonly part of full-length ThrRS, several crenarchaeal species contain
      individual genes encoding the catalytic (ThrRS-cat) and editing domains (ThrRS
      ed). Sulfolobus solfataricus ThrRS-cat was shown to synthesize both Thr-tRNAThr
      and Ser-tRNAThr and to lack editing activity against Ser-tRNAThr. In contrast,
      ThrRS-ed lacks aminoacylation activity but can act as an autonomous protein in
      trans to hydrolyze specifically Ser-tRNAThr, or it can be fused to ThrRS-cat to
      provide the same function in cis. Deletion analyses indicate that ThrRS-ed is
      dispensable for growth of S. solfataricus under standard conditions but is
      required for normal growth in media with elevated serine levels. The growth
      phenotype of the ThrRS-ed deletion strain suggests that retention of the
      discontinuous ThrRS quaternary structure relates to specific physiological
      requirements still evident in certain Archaea.

PMID- 15240875
TI  - Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure,
      pain, and forced-swim tests.
AB  - The pharmacological exploitation of the galanin receptors as drug targets for
      treatment of epilepsy, depression, and pain has been hampered by the lack of
      workable compounds for medicinal chemists from random screening of large chemical
      libraries. The present work uses the tripeptidomimetic galnon and displays its
      presumed pharmacophores on a rigid molecular scaffold. The scaffold is related to
      marine natural products and presents three functional groups near one another in
      space, in a manner reminiscent of a protein surface. An active compound, Galmic,
      was identified from a small synthetic library and tested in vitro and in vivo for
      its affinity and efficacy at galanin receptors. Galmic has micromolar affinity
      for GalR1 receptors (Ki = 34.2 microM) and virtually no affinity for GalR2
      receptors. In vitro, Galmic, like galanin, suppresses long-term potentiation in
      the dentate gyrus; it blocks status epilepticus when injected intrahippocampally
      or administered i.p. Galmic applied i.p. shows antidepressant-like effects in the
      forced-swim test, and it is a potent inhibitor of flinching behavior in the
      inflammatory pain model induced by formalin injection. These data further
      implicate brain and spinal cord galanin receptors as drug targets and provide an
      example of a systemically active compound based on a scaffold that mimics protein
      surfaces.

PMID- 15240876
TI  - Distribution of short paired duplications in mammalian genomes.
AB  - Mammalian genomes are densely populated with long duplicated sequences. In this
      paper, we demonstrate the existence of doublets, short duplications between 25
      and 100 bp, distinct from previously described repeats. Each doublet is a pair of
      exact matches, separated by some distance. The distribution of these intermatch
      distances is strikingly nonrandom. An unexpectedly high number of doublets have
      matches either within 100 bp (adjacent) or at distances tightly concentrated
      approximately 1,000 bp apart (nearby). We focus our study on these proximate
      doublets. First, they tend to have both matches on the same strand. By comparing
      nearby doublets shared in human and chimpanzee, we can also see that these
      doublets seem to arise by an insertion event that produces a copy without
      markedly affecting the surrounding sequence. Most doublets in humans are shared
      with chimpanzee, but many new pairs arose after the divergence of the species.
      Doublets found in human but not chimpanzee are most often composed of almost
      tandem matches, whereas older doublets (found in both species) are more likely to
      have matches spaced by approximately 1 kb, indicating that the nearly tandem
      doublets may be more dynamic. The spacing of doublets is highly conserved. So
      far, we have found clearly recognizable doublets in the following genomes: Homo
      sapiens, Mus musculus, Arabidopsis thaliana, and Caenorhabditis elegans,
      indicating that the mechanism generating these doublets is widespread. A
      mechanism that generates short local duplications while conserving polarity could
      have a profound impact on the evolution of regulatory and protein-coding
      sequences.

PMID- 15240877
TI  - Motif-grafted antibodies containing the replicative interface of cellular PrP are
      specific for PrPSc.
AB  - Prion diseases are closely associated with the conversion of the cellular prion
      protein (PrPC) to an abnormal conformer (PrPSc) [Prusiner, S. B. (1998) Proc.
      Natl. Acad. Sci. USA 95, 13363-13383]. Monoclonal antibodies that bind epitopes
      comprising residues 96-104 and 133-158 of PrPC potently inhibit this process,
      presumably by preventing heterodimeric association of PrPC and PrPSc, and suggest
      that these regions of PrPC may be critical components of the PrPC-PrPSc
      replicative interface. We reasoned that transplanting PrP sequence corresponding
      to these regions into a suitable carrier molecule, such as an antibody, could
      impart specific recognition of disease-associated forms of PrP. To test this
      hypothesis, polypeptides containing PrP sequence between residues 89-112 or 136
      158 were used to replace the extended heavy chain complementarity-determining
      region 3 of an IgG antibody specific for the envelope glycoprotein of HIV-1.
      Herein the resulting engineered PrP-IgGs are shown to bind specifically to
      infective fractions of PrP in mouse, human, and hamster prion-infected tissues,
      but not to PrPC, other cellular components, or the HIV-1 envelope. PrPSc
      reactivity was abolished when the sequence of the PrP 89-112 and 136-158 grafts
      was mutated, scrambled, or N-terminally truncated. Our findings suggest that
      residues within the 89-112 and 136-158 segments of PrPC are key components of one
      face of the PrPC-PrPSc complex. PrPSc-specific antibodies produced by the
      approach described may find widespread application in the study of prion biology
      and replication and in the detection of infectious prions in human and animal
      materials.

PMID- 15240878
TI  - The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth
      factor receptor signaling.
AB  - Cyclin G-associated kinase (GAK) is a serine/threonine kinase that features high
      homology outside its kinase domain with auxilin. Like auxilin, GAK has been shown
      to be a cofactor for uncoating clathrin vesicles in vitro. We investigated
      epidermal growth factor (EGF) receptor-mediated signaling in cells, in which GAK
      is down-regulated by small hairpin RNAs. Here, we report that down-regulation of
      GAK by small hairpin RNA has two pronounced effects on EGF receptor signaling:
      (i) the levels of receptor expression and tyrosine kinase activity go up by >50
      fold; and (ii) the spectrum of downstream signaling is significantly changed. One
      very obvious result is a large increase in the levels of activated extracellular
      signal-regulated kinase 5 and Akt. These two effects of GAK down-regulation
      result from, at least in part, alterations in receptor trafficking, the most
      striking of which is the persistence of EGF receptor in altered cellular
      compartment along with activated extracellular signal-regulated kinase 5. The
      alterations resulting from GAK down-regulation can have distinctive biological
      consequences: In CV1P cells, down-regulation of GAK results in outgrowth of cells
      in soft agar, raising the possibility that loss of GAK function may promote
      tumorigenesis.

PMID- 15240879
TI  - Biophysical constraints on the origin of leaves inferred from the fossil record.
AB  - The molecular tool kit for producing flat-bladed photosynthetic structures
      evolved in marine and terrestrial plants during the middle Paleozoic, but it took
      a further 20 million years before leaves suddenly spread throughout land floras.
      This delay has long been difficult to explain, given the apparent advantage of
      leaves for photosynthetic primary production. Theory and experiments predict that
      exceptionally high atmospheric CO2 levels in the middle Paleozoic delayed the
      origin of leaves by restricting stomatal development. This would have limited
      evaporative cooling, leading to lethal overheating of leaves absorbing large
      quantities of solar energy. Here we test the central prediction of this argument
      with a morphometric analysis of 300 plant fossils from major European
      collections. We show a 25-fold enlargement of leaf blades in two phylogenetically
      independent clades as atmospheric CO2 levels fell during the late Paleozoic.
      Furthermore, preliminary data suggest that the first abrupt increase in leaf size
      was accompanied by an 8-fold rise in stomatal density. These evolutionary
      patterns support the relaxation of biophysical constraints on leaf area predicted
      by theory and point to a significant role for CO2 in plant evolution.

PMID- 15240880
TI  - Central role of suppressors of cytokine signaling proteins in hepatic steatosis,
      insulin resistance, and the metabolic syndrome in the mouse.
AB  - Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver
      are components of the metabolic syndrome, a disease complex that is increasing at
      epidemic rates in westernized countries. Although proinflammatory cytokines have
      been suggested to contribute to the development of these disorders, the molecular
      mechanism is poorly understood. Here we show that overexpression of suppressors
      of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and
      an increase in the key regulator of fatty acid synthesis in liver, sterol
      regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1
      and -3 in obese diabetic mice improves insulin sensitivity, normalizes the
      increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis
      and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP
      1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter
      activity. Thus, SOCS proteins play an important role in pathogenesis of the
      metabolic syndrome by concordantly modulating insulin signaling and cytokine
      signaling.

PMID- 15240881
TI  - Template-assisted filament growth by parallel stacking of tau.
AB  - Tau filaments are found in >20 neurodegenerative diseases. Yet, because of their
      enormous molecular weights and poor tendency to form highly ordered 3D crystal
      lattices, they have evaded high-resolution structure determination. Here, we
      studied 25 derivatized tau mutants by using electron paramagnetic resonance and
      fluorescence spectroscopy to report structural details of tau filaments. Based on
      strong spin exchange and pyrene excimer formation of core residues, we find that
      individual tau proteins form single molecule layers along the fiber axis that
      perfectly stack on top of each other by in-register, parallel alignment of beta
      strands. We suggest a model of filament growth wherein the existing filament
      serves as a template for the incoming, unfolded tau molecule, resulting in a new
      structured layer with maximized hydrogen-bonded contact surface and side-chain
      stacking.

PMID- 15240882
TI  - Thyroid hormone receptor alpha is a molecular switch of cardiac function between
      fetal and postnatal life.
AB  - Thyroid hormones are involved in the regulation of many physiological processes
      and regulate gene transcription by binding to their nuclear receptors TRalpha and
      TRbeta. In the absence of triiodothyronine (T3), the unliganded receptors
      (aporeceptors) do bind DNA and repress the transcription of target genes. The
      role of thyroid hormone aporeceptors as repressors was observed in hypothyroid
      adult mice, but its physiological relevance in nonpathological hypothyroid
      conditions remained to be determined. Here we show that, in the normal mouse
      fetus, TRalpha aporeceptors repress heart rate as well as the expression of
      TRbeta and several genes encoding ion channels involved in cardiac contractile
      activity. Right after birth, when T3 concentration sharply increases, liganded
      TRalpha (holoreceptors) turn on the expression of some of these same genes
      concomitantly with heart rate increase. These data describe a physiological
      situation under which conversion of TRalpha from apo-receptors into holo
      receptors, upon changes in T3 availability, plays a determinant role in a
      developmental process.

PMID- 15240883
TI  - Genome-wide analysis of repressor element 1 silencing transcription factor/neuron
      restrictive silencing factor (REST/NRSF) target genes.
AB  - The completion of whole genome sequencing projects has provided the genetic
      instructions of life. However, whereas the identification of gene coding regions
      has progressed, the mapping of transcriptional regulatory motifs has moved more
      slowly. To understand how distinct expression profiles can be established and
      maintained, a greater understanding of these sequences and their trans-acting
      factors is required. Herein we have used a combined in silico and biochemical
      approach to identify binding sites [repressor element 1/neuron-restrictive
      silencer element (RE1/NRSE)] and potential target genes of RE1 silencing
      transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the
      human, mouse, and Fugu rubripes genomes. We have used this genome-wide analysis
      to identify 1,892 human, 1,894 mouse, and 554 Fugu RE1/NRSEs and present their
      location and gene linkages in a searchable database. Furthermore, we identified
      an in vivo hierarchy in which distinct subsets of RE1/NRSEs interact with
      endogenous levels of REST/NRSF, whereas others function as bona fide
      transcriptional control elements only in the presence of elevated levels of
      REST/NRSF. These data show that individual RE1/NRSE sites interact differentially
      with REST/NRSF within a particular cell type. This combined bioinformatic and
      biochemical approach serves to illustrate the selective manner in which a
      transcription factor interacts with its potential binding sites and regulates
      target genes. In addition, this approach provides a unique whole-genome map for a
      given transcription factor-binding site implicated in establishing specific
      patterns of neuronal gene expression.

PMID- 15240884
TI  - Nanos suppresses somatic cell fate in Drosophila germ line.
AB  - Nanos (Nos) is one of the evolutionarily conserved proteins known to direct germ
      line development. In Drosophila, maternal Nos protein maintains transcriptional
      quiescence in the germ-line progenitors or pole cells to repress ectopic
      expression of somatic genes. Here we show that maternal Nos is required to
      establish and maintain germ-line identity by preventing apoptosis and somatic
      cell fate. The pole cells lacking maternal Nos were degraded by apoptosis during
      mid to late embryogenesis. When apoptosis was suppressed by Df(3L)H99, some pole
      cells lacking Nos adopted somatic cell fates. These pole cells expressed somatic
      markers ectopically and lost the germ-line marker Vasa. We further found that
      some Nos-negative pole cells were able to migrate into the gonads, but they
      failed to develop as functional germ cells during postembryonic stages. We
      propose a model in which Nos establishes germ-line/soma dichotomy and is also
      required to maintain germ-line fate.

PMID- 15240885
TI  - A role for Galpha12/Galpha13 in p120ctn regulation.
AB  - The catenin p120 (p120ctn) is an armadillo repeat domain protein that binds to
      cadherins and has been shown to facilitate strong cell-cell adhesion. We have
      investigated a possible link between heterotrimeric G proteins and p120ctn, and
      found that both Galpha12 and Galpha13 can completely and selectively abrogate the
      p120ctn-induced branching phenotype in different cell types. Consistent with
      these observations, the expression of Galpha12 or Galpha13 compensates for the
      reduction of Rho activity induced by p120ctn. On the other hand, p120ctn can be
      selectively coimmunoprecipitated with Galpha12, and the coimmunoprecipitation was
      favored by activation of the G protein. A specific interaction between p120ctn
      and Galpha12Q231L was also observed in in vitro binding experiments. In addition,
      p120ctn can be immunoprecipitated along with Galpha12Q231L in L cells in absence
      of E-cadherin. Interestingly, the expression of Galpha12Q231L increases the
      amount of p120ctn associated with E-cadherin. These findings demonstrate that
      Galpha12 and p120ctn are binding partners, and they also suggest a role for
      Galpha12 in regulating p120ctn activity and its interaction with cadherins. We
      propose that the Galpha12-p120ctn interaction acts as a molecular switch, which
      regulates cadherin-mediated cell-cell adhesion.

PMID- 15240886
TI  - AML1/Runx1 is important for the development of hindbrain cholinergic
      branchiovisceral motor neurons and selected cranial sensory neurons.
AB  - The mechanisms that regulate the acquisition of distinctive neuronal traits in
      the developing nervous system are poorly defined. It is shown here that the
      mammalian runt-related gene Runx1 is expressed in selected populations of
      postmitotic neurons of the embryonic central and peripheral nervous systems.
      These include cholinergic branchial and visceral motor neurons in the hindbrain,
      restricted populations of somatic motor neurons of the median and lateral motor
      columns in the spinal cord, as well as nociceptive and mechanoreceptor neurons in
      trigeminal and vestibulocochlear ganglia. In mouse embryos lacking Runx1
      activity, hindbrain branchiovisceral motor neuron precursors of the cholinergic
      lineage are correctly specified but then fail to progress to a more
      differentiated state and undergo increased cell death, resulting in a neuronal
      loss in the mantle layer. In contrast, the development of cholinergic somatic
      motor neurons is unaffected. Runx1 inactivation also leads to a loss of selected
      sensory neurons in trigeminal and vestibulocochlear ganglia. These findings
      uncover previously unrecognized roles for Runx1 in the regulation of mammalian
      neuronal subtype development.

PMID- 15240887
TI  - Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound
      ovine prion scrapie-susceptibility variants.
AB  - Prion diseases are associated with the conversion of the alpha-helix rich prion
      protein (PrPC) into a beta-structure-rich insoluble conformer (PrPSc) that is
      thought to be infectious. The mechanism for the PrPC-->PrPSc conversion and its
      relationship with the pathological effects of prion diseases are poorly
      understood, partly because of our limited knowledge of the structure of PrPSc. In
      particular, the way in which mutations in the PRNP gene yield variants that
      confer different susceptibilities to disease needs to be clarified. We report
      here the 2.5-A-resolution crystal structures of three scrapie-susceptibility
      ovine PrP variants complexed with an antibody that binds to PrPC and to PrPSc;
      they identify two important features of the PrPC-->PrPSc conversion. First, the
      epitope of the antibody mainly consists of the last two turns of ovine PrP second
      alpha-helix. We show that this is a structural invariant in the PrPC-->PrPSc
      conversion; taken together with biochemical data, this leads to a model of the
      conformational change in which the two PrPC C-terminal alpha-helices are
      conserved in PrPSc, whereas secondary structure changes are located in the N
      terminal alpha-helix. Second, comparison of the structures of scrapie-sensitivity
      variants defines local changes in distant parts of the protein that account for
      the observed differences of PrPC stability, resistant variants being destabilized
      compared with sensitive ones. Additive contributions of these sensitivity
      modulating mutations to resistance suggest a possible causal relationship between
      scrapie resistance and lowered stability of the PrP protein.

PMID- 15240888
TI  - Information constraints and the precision of adaptation: sex ratio manipulation
      in wasps.
AB  - Sex allocation theory offers excellent opportunities for studying the precision
      of adaptation. One of the best-supported areas in the field of sex allocation is
      Hamilton's theory of local mate competition, which predicts female-biased
      offspring sex ratios when populations are structured such that mating takes place
      locally before females disperse. As predicted by local mate competition theory,
      females of numerous species, especially parasitoid wasps, have been shown to lay
      a less female-biased sex ratio as the number of females simultaneously laying
      eggs on a patch increases. It has usually been assumed that this sex ratio
      adjustment comes through individuals adjusting their behavior directly in
      response to the presence of other females. Here we show that in the parasitoid
      wasp Nasonia vitripennis, this shift in offspring sex ratios is primarily caused
      by the presence of eggs laid by other females and to a lesser extent by the
      presence of other females. We confirm that females are behaving as predicted by
      theory, but the way in which they do so is not as straightforward as is often
      assumed. Instead, even when there are multiple females on a patch, individuals
      still use the cues that are more commonly associated with sex ratio adjustment in
      response to sequential visits to a patch by females. This result provides a
      possible explanation for the observed variation in N. vitripennis sex ratios.
      More generally, it confirms the need to consider the mechanistic basis of a
      behavior to understand fully its adaptive value.

PMID- 15240889
TI  - Cre-lox-regulated conditional RNA interference from transgenes.
AB  - We have generated two lentiviral vectors for conditional, Cre-lox-regulated, RNA
      interference. One vector allows for conditional activation, whereas the other
      permits conditional inactivation of short hairpin RNA (shRNA) expression. The
      former is based on a strategy in which the mouse U6 promoter has been modified by
      including a hybrid between a LoxP site and a TATA box. The ability to efficiently
      control shRNA expression by using these vectors was shown in cell-based
      experiments by knocking down p53, nucleophosmin and DNA methyltransferase 1. We
      also demonstrate the usefulness of this approach to achieve conditional, tissue
      specific RNA interference in Cre-expressing transgenic mice. Combined with the
      growing array of Cre expression strategies, these vectors allow spatial and
      temporal control of shRNA expression in vivo and should facilitate functional
      genetic analysis in mammals.

PMID- 15240890
TI  - Lipid- and mechanosensitivities of sodium/hydrogen exchangers analyzed by
      electrical methods.
AB  - Sodium/hydrogen exchangers (NHEs) are ubiquitous ion transporters that serve
      multiple cell functions. We have studied two mammalian isoforms, NHE1
      (ubiquitous) and NHE3 (epithelial-specific), by measuring extracellular proton
      (H+) gradients during whole-cell patch clamp with perfusion of the cell interior.
      Maximal Na(+)-dependent H+ fluxes (JH+) are equivalent to currents >20 pA for
      NHE1 in Chinese hamster ovary fibroblasts, >200 pA for NHE1 in guinea pig
      ventricular myocytes, and 5-10 pA for NHE3 in opossum kidney cells. The fluxes
      are blocked by an NHE inhibitor, ethylisopropylamiloride, and are absent in NHE
      deficient AP-1 cells. NHE1 activity is stable with perfusion of nonhydrolyzable
      ATP [adenosine 5'-(beta,gamma-imido)triphosphate], is abolished by ATP depletion
      (2 deoxy-D-glucose with oligomycin or perfusion of apyrase), can be restored with
      phosphatidylinositol 4,5-bisphosphate, and is unaffected by actin cytoskeleton
      disruption (latrunculin or pipette perfusion of gelsolin). NHE3 (but not NHE1) is
      reversibly activated by phosphatidylinositol 3,4,5-trisphosphate. Both NHE1 and
      NHE3 activities are disrupted in giant patches during gigaohm seal formation.
      NHE1 (but not NHE3) is reversibly activated by cell shrinkage, even at neutral
      cytoplasmic pH without ATP, and inhibited by cell swelling. NHE1 in Chinese
      hamster ovary fibroblasts (but not NHE3 in opossum kidney cells) is inhibited by
      agents that thin the membrane (L-alpha-lysophosphatidylcholine and octyl-beta-D
      glucopyranoside) and activated by cholesterol enrichment, which thickens
      membranes. Expressed in AP-1 cells, however, NHE1 is insensitive to these agents
      but remains sensitive to volume changes. Thus, changes of hydrophobic mismatch
      can modulate NHE1 but do not underlie its volume sensitivity.

PMID- 15240891
TI  - Arabidopsis myosin XI mutant is defective in organelle movement and polar auxin
      transport.
AB  - Myosins are eukaryotic molecular motors moving along actin filaments. Only a
      small set of myosin classes is present in plants, in which myosins have been
      found to play a role in cytoplasmic streaming and chloroplast movement. Whereas
      most studies have been done on green algae, more recent data suggest a role of
      higher plant myosin at the postcytokinetic cell wall. Here we characterize a loss
      of-function mutation for a myosin of plant-specific class XI and demonstrate
      myosin functions during plant development in Arabidopsis. T-DNA insertion in MYA2
      caused pleiotropic effects, including flower sterility and dwarf growth.
      Elongation of epidermal cells, such as in hypocotyls and anther filaments, was
      reduced by up to 50% of normal length. This effect on anther filaments is
      responsible for flower sterility. In the meristems of root tips, it was evident
      that cell division was delayed and that cell plates were mislocated. Like
      zwichel, a kinesin-related mutation causing two-branched trichomes, the mya2
      knockout causes branching defects, but here the trichomes remained unbranched.
      Growth was also impaired in pollen tubes and root hairs, cells that are highly
      dependent on vesicle transport. A failure in vesicle flow could be directly
      confirmed, because cytoplasmic streaming of vesicles and, more so, of large
      endoplasmic reticulum-based organelles was slowed. The defect in vesicle
      trafficking was accompanied by failures in basipetal auxin transport, measured in
      stem segments of inflorescences. This result strongly suggests a causal link
      between auxin-dependent processes and the distribution of vesicles and membrane
      bound molecules by plant myosin.

PMID- 15240892
TI  - Switching desaturase enzyme specificity by alternate subcellular targeting.
AB  - The functionality, substrate specificity, and regiospecificity of enzymes
      typically evolve by the accumulation of mutations in the catalytic portion of the
      enzyme until new properties arise. However, emerging evidence suggests enzyme
      functionality can also be influenced by metabolic context. When the plastidial
      Arabidopsis 16:0Delta7 desaturase FAD5 (ADS3) was retargeted to the cytoplasm,
      regiospecificity shifted 70-fold, Delta7 to Delta9. Conversely, retargeting of
      two related cytoplasmic 16:0Delta9 Arabidopsis desaturases (ADS1 and ADS2) to the
      plastid, shifted regiospecificity approximately 25-fold, Delta9 to Delta7. All
      three desaturases exhibited Delta9 regiospecificity when expressed in yeast, with
      desaturated products found predominantly on phosphatidylcholine. Coexpression of
      each enzyme with cucumber monogalactosyldiacylglycerol (MGDG) synthase in yeast
      conferred Delta7 desaturation, with 16:1Delta7 accumulating specifically on the
      plastidial lipid MGDG. Positional analysis is consistent with ADS desaturation of
      16:0 on MGDG. The lipid headgroup acts as a molecular switch for desaturase
      regiospecificity. FAD5 Delta7 regiospecificity is thus attributable to plastidial
      retargeting of the enzyme by addition of a transit peptide to a cytoplasmic
      Delta9 desaturase rather than the numerous sequence differences within the
      catalytic portion of ADS enzymes. The MGDG-dependent desaturase activity enabled
      plants to synthesize 16:1Delta7 and its abundant metabolite, 16:3Delta(7,10,13).
      Bioinformatics analysis of the Arabidopsis genome identified 239 protein families
      that contain members predicted to reside in different subcellular compartments,
      suggesting alternative targeting is widespread. Alternative targeting of
      bifunctional or multifunctional enzymes can exploit eukaryotic subcellular
      organization to create metabolic diversity by permitting isozymes to interact
      with different substrates and thus create different products in alternate
      compartments.

PMID- 15240893
TI  - Effect of aqueous tobacco smoke extract and shear stress on PECAM-1 expression
      and cell motility in human uterine endothelial cells.
AB  - Tobacco smoke constituents have several adverse effects on endothelial cells.
      Exposure to tobacco smoke during pregnancy is associated with adverse effects on
      pregnancy outcome possibly related to endothelial dysfunction. Platelet
      endothelial cell adhesion molecule-1 (PECAM-1) is an important regulator of
      endothelial function. This study tests the idea that an aqueous extract of
      cigarette smoke alters the expression of PECAM-1 in uterine endothelial cells.
      Human uterine microvascular endothelial cells were cultured in cigarette smoke
      conditioned medium (CSM) under arterial physiological flow conditions (shear or
      frictional stress in the range 7.5-15 dyne/cm(2)) and the expression of PECAM-1
      was assessed by immunofluorescence microscopy and Western blotting. Thick
      reticular PECAM-1-associated bands found at cell-cell junctions in static
      cultures became significantly thinner or disappeared when the cells were exposed
      to shear stress or to CSM for 24 h. This diminution at cell junctions was
      accompanied by increased punctate cytoplasmic/cell surface staining. Under shear
      stress conditions, PECAM-1 was equally distributed between cell surface and
      intracellular sites. In contrast, when cells were exposed to both shear stress
      and CSM, PECAM-1 was predominantly localized to the cell surface. It was shown
      that shear stress increased endothelial cell migration and that CSM abrogated
      this effect. These results suggest that, under shear stress conditions, PECAM-1
      is not predominantly concentrated at intercellular junctions in uterine
      endothelial cells. Exposure of cells to unidentified soluble components of
      cigarette smoke leads to alterations in PECAM-1 distribution that may cause
      endothelial dysfunction. If this occurs in vivo it could contribute to the
      adverse effects on pregnancy outcome associated with exposure to cigarette smoke.

PMID- 15240894
TI  - The effect of divalent cations on neuronal nitric oxide synthase activity.
AB  - Neuronal nitric oxide synthase (NOS I) is a Ca(2+)/calmodulin-binding enzyme that
      generates nitric oxide (NO*) and L-citrulline from the oxidation of L-arginine,
      and superoxide (O(2)*(-)) from the one-electron reduction of oxygen (O(2)).
      Nitric oxide in particular has been implicated in many physiological processes,
      including vasodilator tone, hypertension, and the development and properties of
      neuronal function. Unlike Ca(2+), which is tightly regulated in the cell, many
      other divalent cations are unfettered and can compete for the four Ca(2+) binding
      sites on calmodulin. The results presented in this article survey the effects of
      various divalent metal ions on NOS I-mediated catalysis. As in the case of
      Ca(2+), we demonstrate that Ni(2+), Ba(2+), and Mn(2+) can activate NOS I to
      metabolize L-arginine to L-citrulline and NO*, and afford O(2)*(-) in the absence
      of L-arginine. In contrast, Cd(2+) did not activate NOS I to produce either NO*
      or O(2)*(-), and the combination of Ca(2+) and either Cd(2+), Ni(2+), or Mn(2+)
      inhibited enzyme activity. These interactions may initiate cellular toxicity by
      negatively affecting NOS I activity through production of NO*, O(2)*(-) and
      products derived from these free radicals.

PMID- 15240895
TI  - Adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and effects on male
      reproductive organs in three differentially TCDD-susceptible rat lines.
AB  - The contribution of genetic factors to adult male reproductive system toxicity of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was analyzed in three rat lines
      differentially resistant to TCDD acute lethality: line A, B, and C rats
      (selectively bred from TCDD-resistant Han/Wistar [Kuopio; H/W] and TCDD-sensitive
      Long-Evans [Turku/AB; L-E] rats). The resistance is linked to a mutated H/W-type
      aryl hydrocarbon receptor allele in line A and to an H/W-type unknown "B" allele
      in line B. Line C rats do not have resistance alleles. Mature male line A, B and
      C rats were given single oral doses up to 1000, 300, and 30 micrograms/kg TCDD,
      respectively. The dose-responses of TCDD effects on male reproductive organ
      weights, sperm numbers, and serum testosterone concentrations were analyzed 17
      days after exposure. Serum testosterone concentrations were decreased by the
      highest doses of TCDD, and there were no major sensitivity differences among the
      rat lines. Correspondingly, the decrease in relative weight of ventral prostate
      and seminal vesicles was seen only after a dose of >/=100 micrograms/kg TCDD.
      Thus the effect was observed only in resistant lines A and B. The relative
      weights of testes and epididymides were not affected. Significant decrease in
      spermatogenesis was observed in each rat line, but the amount of decrease was
      reduced by resistance alleles. The highest TCDD dose decreased the daily sperm
      production by 37, 38, and 60% in line A, B, and C rats, respectively. Therefore,
      the resistance alleles appear to selectively modify the TCDD effects on the adult
      male reproductive system. The fact that the influence of resistance alleles on
      spermatogenesis is different from that on androgenic status indicates that the
      effect of TCDD on sperm numbers is not fully related to decreased serum
      testosterone.

PMID- 15240896
TI  - p38 and Src-ERK1/2 pathways regulate crystalline silica-induced chemokine release
      in pulmonary epithelial cells.
AB  - Crystalline silica has been shown to trigger pulmonary inflammation both in vivo
      and in vitro, but the underlying molecular mechanisms remain unclear. In the
      present study we focus on the intracellular signaling pathways regulating
      chemokine release from lung epithelial cells after crystalline silica exposure.
      Our results show that silica particles induced a concentration- and time
      dependent increase in interleukin (IL)-8 release from the human epithelial lung
      cell line A549. The IL-8 induction was significantly attenuated by inhibitors of
      the mitogen-activated protein kinases (MAPKs), p38 (SB202190) and extracellular
      signal-regulated kinase (ERK)-1 and -2 (PD98059), as well as a general protein
      tyrosine kinase (PTK) inhibitor (genistein). However, IL-8 induction was most
      efficiently inhibited by the Src family kinase (SFK) inhibitor, PP2, suggesting a
      crucial role of SFKs in regulating silica-induced IL-8 release from A549 cells.
      Silica exposure induced phosphorylation of the MAPKs p38 and ERK1/2, but not JNK
      or ERK5. Silica also induced a significant phosphorylation of SFKs. Moreover, PP2
      inhibited silica-induced phospho-ERK1/2 to near-control levels, whereas phospho
      p38 was not significantly reduced by the SFK inhibitor. Our results suggest the
      presence of two separate signaling pathways which are important in the regulation
      of silica-induced IL-8 release from A549 cells; one involving SFK-dependent
      activation of ERK1/2, and the other activation of p38, at least partly
      independent of SFKs. Experiments with primary type 2 (T2) cells from rat lungs
      suggest that crystalline silica-induced release of macrophage inflammatory
      protein (MIP)-2 is regulated through similar mechanisms.

PMID- 15240897
TI  - Investigations of strain and/or gender differences in developmental neurotoxic
      effects of polybrominated diphenyl ethers in mice.
AB  - Polybrominated diphenyl ethers (PBDEs), one class of flame retardants used to
      suppress or inhibit the risk of fire, are regularly found in the environment and
      in human milk. The present study shows that neonatal exposure to a widely,
      environmentally found PBDE, 2,2',4,4',5-pentaBDE (PBDE 99), can induce
      developmental neurotoxic effects, such as changes in spontaneous behavior
      (hyperactivity), effects that are dose-response related and worsen with age.
      These changes are seen in C57/Bl mice of both sexes. Neonatal C57/Bl male and
      female mice were orally exposed on day 10 to 0.4, 0.8, 4.0, 8.0, or 16 mg PBDE
      99/kg body weight. Spontaneous behavior (locomotion, rearing, and total activity)
      was observed in two-, five-, and eight-month-old mice. The behavior tests showed
      that the effects were dose-response and time-response related for both male and
      female mice. The observed developmental neurotoxic effects seen for PBDE 99, in
      C57/Bl mice, are similar to effects seen for 2,2',4,4'-tetraBDE (PBDE 47), PBDE
      99, 2,2',4,4',5,5'- hexaBDE (PBDE 153), 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE
      209) and for certain PCBs, in male NMRI mice. Furthermore, the effects of PBDEs
      appear to be as potent in female mice as in male mice, and as potent in C57/Bl
      mice as in NMRI mice, concerning developmental neurotoxicity.

PMID- 15240898
TI  - Teaching resource. Canonical Wnt/beta-catenin signaling.
AB  - This animation provides an interactive presentation of the Wnt signaling pathway
      as it may occur in multiple cell types. This animation would be useful in
      teaching developmental biology, immunology, and cell signaling courses.
      Activation of Wnt pathways can modulate cell proliferation, cell survival, cell
      behavior, and cell fate. In the basal, unstimulated state in the absence of
      ligand, there is a constitutively active kinase, which phosphorylates target
      proteins, resulting in their degradation. Thus, the presence of the ligand Wnt
      inactivates the kinase allowing accumulation of beta-catenin, which then
      translocates to the nucleus and acts as a transcriptional regulator.

PMID- 15240899
TI  - Teaching resource. Beta-catenin signaling and axis specification.
AB  - This animation provides a representation of the beta-catenin signaling pathway in
      response to fertilization and the process of axis specification that occurs early
      in development. The process shown is based on analysis of embryos of the
      amphibian Xenopus. This animation would be useful in illustrating events that
      occur early in embryogenesis and how embryos become polarized as a consequence of
      localized signaling processes.

PMID- 15240901
TI  - Genetic correlations: transient truths of adaptive evolution.

PMID- 15240902
TI  - Immunocompetence in Drosophila: linking genetic to phenotypic variation.

PMID- 15240903
TI  - [Hypothesis] On the genetic basis of temperature compensation of circadian
      clocks.

PMID- 15240904
TI  - Are bigger flies always better: the role of genes and environment.

PMID- 15240905
TI  - Studies in quantitative inheritance. XI. Genetic and environmental correlation
      between body size and egg production in Drosophila melanogaster. 1957.

PMID- 15240906
TI  - Engineered XcmI cassette-containing vector for PCR-based phylogenetic analyses.

PMID- 15240907
TI  - Refinement of the locus for non-syndromic sensorineural deafness (DFN2).
AB  - Non-syndromic X-linked deafness is a rare form of genetic deafness in humans
      accounting for a small proportion of all hereditary hearing loss. Different
      clinical forms of non-syndromic X-linked deafness have been described, and most
      of these have been mapped. Here, we report a Chinese family affected by a
      congenital profound sensorineural hearing loss. All phenotypes of this family are
      clinically compatible with non-syndromic sensorineural deafness (DFN2). A maximum
      two-point Lod score of 2.32 was obtained at marker DXS6797 (theta = 0.00).
      Recombinants define a region of 4.3 cM flanked by markers DXS6799 and GATA172D05.
      This region overlaps the previously reported DFN2 region by 2.0 cM.

PMID- 15240908
TI  - Mitochondrial DNA sequence variation in the Anatolian Peninsula (Turkey).
AB  - Throughout human history, the region known today as the Anatolian peninsula
      (Turkey) has served as a junction connecting the Middle East, Europe and Central
      Asia, and, thus, has been subject to major population movements. The present
      study is undertaken to obtain information about the distribution of the existing
      mitochondrial D-loop sequence variations in the Turkish population of Anatolia. A
      few studies have previously reported mtDNA sequences in Turks. We attempted to
      extend these results by analysing a cohort that is not only larger, but also more
      representative of the Turkish population living in Anatolia. In order to obtain a
      descriptive picture for the phylogenetic distribution of the mitochondrial genome
      within Turkey, we analysed mitochondrial D-loop region sequence variations in 75
      individuals from different parts of Anatolia by direct sequencing. Analysis of
      the two hypervariable segments within the noncoding region of the mitochondrial
      genome revealed the existence of 81 nucleotide mutations at 79 sites. The
      neighbour-joining tree of Kimura's distance matrix has revealed the presence of
      six main clusters, of which H and U are the most common. The data obtained are
      also compared with several European and Turkic Central Asian populations.

PMID- 15240909
TI  - Deciphering diversity in populations of various linguistic and ethnic
      affiliations of different geographical regions of India: analysis based on 15
      microsatellite markers.
AB  - The extent of genetic polymorphism at fifteen autosomal microsatellite markers in
      54 ethnically, linguistically and geographically diverse human populations of
      India was studied to decipher intrapopulation diversity. The parameters used to
      quantify intrapopulation diversity were average allele diversity, average
      heterozygosity, allele range (base pairs), and number of alleles. Multilocus
      genotype frequencies calculated for selected populations were utilized for
      testing conformity with the assumption of Hardy-Weinberg equilibrium. The exact
      test values, after Bonferroni correction, showed significant deviation amongst
      Gowda (vWA, Penta E); Dhangar, Satnami and Gounder (D8S1179); Hmar (FGA); Kuki
      and Balti (vWA) groups. Relatively low number of alleles and allelic diversity
      (base-pairs size) had been observed in populations of central India as compared
      with southern and northern regions of the country. The communities of Indo
      Caucasoid ethnic origin and Indo-European linguistic family (Kshatriya of Uttar
      Pradesh) showed highest allelic diversity, as well as rare alleles, not reported
      in any other Indian populations. Analysis based on average heterozygosity was
      also found to be lowest among the populations of central India (0.729) and
      highest among the populations from north (0.777) and west (0.784) regions of the
      country, having Indo-Caucasoid ethnic origin and Austro-Asiatic linguistic
      affiliation. The maximum power of discrimination (85%-89%) had been observed at
      loci FGA, Penta E, D18S51 and D21S11, suggested high intrapopulation diversity in
      India. Genetic diversity revealed by STR markers was consistent with the known
      demographic histories of populations. Thus, the present study clearly
      demonstrated that the intrapopulation diversity is not only present at the
      national level, but also within smaller geographical regions of the country. This
      is the first attempt to understand the extent of diversity within populations of
      India at such a large scale at genomic level.

PMID- 15240910
TI  - Allelic structure and distribution of 103 STR loci in a Southern Tunisian
      population.
AB  - Genotypes of 103 short tandem repeat (STR) markers distributed at an average of
      40 cM intervals throughout the genome were determined for 40 individuals from the
      village of BirEl Hfai (BEH). This village of approximately 31,000 individuals is
      localized in the south-west of Tunisia. The allele frequency distributions in BEH
      were compared with those obtained for individuals in the CEPH (Centre d'Etude du
      Polymorphisme Humain) data using a Kolmogorov-Smirnov two-sample test. Fourteen
      out of the 103 markers (13.2%) showed significant differences (P<0.05) in
      distribution between the two populations. Population heterogeneity in BEH was
      indicated by an excess of observed homozygosity deviations from Hardy-Weinberg
      equilibrium at three loci (P<0.0005). No evidence for genotypic disequilibrium
      was found for any of the marker pairs. This demonstrated that in spite of a high
      inbreeding level in the population, few markers showed evidence for a different
      pattern of allelic distribution compared to CEPH.

PMID- 15240911
TI  - Circadian clocks and life-history related traits: is pupation height affected by
      circadian organization in Drosophila melanogaster?
AB  - In D. melanogaster, the observation of greater pupation height under constant
      darkness than under constant light has been explained by the hypothesis that
      light has an inhibitory effect on larval wandering behaviour, preventing larvae
      from crawling higher up the walls of culture vials prior to pupation. If this is
      the only role of light in affecting pupation height, then various light : dark
      regimes would be predicted to yield pupation heights intermediate between those
      seen in constant light and constant darkness. We tested this hypothesis by
      measuring pupation height under various light : dark regimes in four laboratory
      populations of Drosophila melanogaster. Pupation height was the greatest in
      constant darkness, intermediate in constant light, and the least in a light/dark
      regime of LD 14:14 h. The results clearly suggest that there is more to light
      regime effects on pupation height than mere behavioural inhibition of wandering
      larvae, and that circadian organization may play some role in determining
      pupation height, although the details of this role are not yet clear. We briefly
      discuss these results in the context of the possible involvement of circadian
      clocks in life-history evolution.

PMID- 15240913
TI  - C. C. Li (1912-2003): his science and his spirit.

PMID- 15240915
TI  - Human Embryonic Stem Cell Research: No Way Around a Scientific Bottleneck.

PMID- 15240916
TI  - Tetranectin Binds to the Kringle 1-4 Form of Angiostatin and Modifies Its
      Functional Activity.
AB  - Tetranectin is a plasminogen kringle 4 domain-binding protein present in plasma
      and various tissue locations. Decreased plasma tetranectin or increased
      tetranectin in stroma of cancers correlates with cancer progression and adverse
      prognosis. A possible mechanism through which tetranectin could influence cancer
      progression is by altering activities of plasminogen or the plasminogen fragment,
      angiostatin. Tetranectin was found to bind to the kringle 1-4 form of angiostatin
      (AST $;{?text{K1-4}}$ ). In addition, tetranectin inhibited binding of
      plasminogen or AST $;{?text{K1-4}}$ to extracellular matrix (ECM) deposited by
      endothelial cells. Finally, tetranectin partially counteracted the ability of AST
      $;{?text{K1-4}}$ to inhibit proliferation of endothelial cells. This latter
      effect of tetranectin was specific for AST $;{?text{K1-4}}$ since it did not
      counteract the antiproliferative activities of the kringle 1-3 form of
      angiostatin (AST $;{?text{K1-3}}$ ) or endostatin. These findings suggest that
      tetranectin may modulate angiogenesis through interactions with AST.

PMID- 15240917
TI  - Survival of Human Neurofibroma in Immunodeficient Mice and Initial Results of
      Therapy With Pirfenidone.
AB  - Neurofibromatosis type I is a common tumor predisposing disease in humans.
      Surgical therapy can be applied only in selected patients with resectable masses.
      Hence, development of new therapies for this disease is urgent. We used human
      neurofibroma implants in mice with severe combined immunodeficiency (SCID) as a
      model to test the toxicity and potential efficacy of pirfenidone, a new
      therapeutic agent. Two hundred twelve human neurofibromas were transplanted into
      various locations in 59 experimental animals, and 30 mice with implants received
      oral pirfenidone for up to six weeks. Survival of neurofibromas in animals
      treated with pirfenidone was lower than in the control group $(P=.02)$. Tumors
      did not change histologic appearance or vascularization in response to
      pirfenidone. Treatment with pirfenidone, a new antifibrotic agent, inhibits
      survival of some tumors without causing toxicity in animals.

PMID- 15240912
TI  - Structural and functional analysis of rice genome.
AB  - Rice is an excellent system for plant genomics as it represents a modest size
      genome of 430 Mb. It feeds more than half the population of the world. Draft
      sequences of the rice genome, derived by whole-genome shotgun approach at
      relatively low coverage (4-6 X), were published and the International Rice Genome
      Sequencing Project (IRGSP) declared high quality (>10 X), genetically anchored,
      phase 2 level sequence in 2002. In addition, phase 3 level finished sequence of
      chromosomes 1, 4 and 10 (out of 12 chromosomes of rice) has already been reported
      by scientists from IRGSP consortium. Various estimates of genes in rice place the
      number at >50,000. Already, over 28,000 full-length cDNAs have been sequenced,
      most of which map to genetically anchored genome sequence. Such information is
      very useful in revealing novel features of macro- and micro-level synteny of rice
      genome with other cereals. Microarray analysis is unraveling the identity of rice
      genes expressing in temporal and spatial manner and should help target candidate
      genes useful for improving traits of agronomic importance. Simultaneously,
      functional analysis of rice genome has been initiated by marker-based
      characterization of useful genes and employing functional knock-outs created by
      mutation or gene tagging. Integration of this enormous information is expected to
      catalyze tremendous activity on basic and applied aspects of rice genomics.

PMID- 15240918
TI  - Differential Behavior Between Isolated and Aggregated Rabbit Auricular
      Chondrocytes on Plastic Surfaces.
AB  - A knowledge of the behavior of chondrocytes in culture is relevant for tissue
      engineering. Chondrocytes dedifferentiate to a fibroblast-like phenotype on
      plastic surfaces. Dedifferentiation is reversible if these cells are then
      cultured in suspension. In this report a description is given of how when
      chondrocyte aggregates formed in suspension are next seeded on plastic, most of
      them attach as round or polygonal cells. This morphological differentiation, with
      synthesis of type II collagen, is stable for long culture periods. This simple
      method can be of use as a model for studies of chondrocyte behavior on plastic.
      The results indicate that in addition to culture conditions, such as cell
      isolation method or cell density, chondrocyte behavior on plastic depends on the
      presence of aggregates.

PMID- 15240919
TI  - Novel Marine Compounds: Anticancer or Genotoxic?
AB  - In the past several decades, marine organisms have generously gifted to the
      pharmaceutical industries numerous naturally bioactive compounds with antiviral,
      antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer
      potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have
      been commercially developed from marine compounds while several others are
      currently in different clinical trials. Majority of these compounds were tested
      in the tumor xenograft models, however, lack of anticancer potential data in the
      chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models
      might have cost some of the marine anticancer compounds an early exit from the
      clinical trials. This review critically discusses importance of preclinical
      evaluation, failure of human clinical trials with certain potential anticancer
      agents, the screening tests used, and choice of biomarkers.

PMID- 15240920
TI  - 5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity.
AB  - 5-lipoxygenase (5-LO) pathway is the major source of potent proinflammatory
      leukotrienes (LTs) issued from the metabolism of arachidonic acid (AA), and best
      known for their roles in the pathogenesis of asthma. These lipid mediators are
      mainly released from myeloid cells and may act as physiological autocrine and
      paracrine signalling molecules, and play a central role in regulating the
      interaction between innate and adaptive immunity. The biological actions of LTs
      including their immunoregulatory and proinflammatory effects are mediated through
      extracellular specific G-protein-coupled receptors. Despite their role in
      inflammatory cells, such as neutrophils and macrophages, LTs may have important
      effects on dendritic cells (DC)-mediated adaptive immunity. Several lines of
      evidence show that DC not only are important source of LTs, but also become
      targets of their actions by producing other lipid mediators and proinflammatory
      molecules. This review focuses on advances in 5-LO pathway biology, the
      production of LTs from DC and their role on various cells of immune system and in
      adaptive immunity.

PMID- 15240921
TI  - Serial Analysis of Gene Expression: Applications in Malaria Parasite, Yeast,
      Plant, and Animal Studies.
AB  - The serial analysis of gene expression (SAGE) method is based on the isolation of
      unique sequence tags from individual transcripts and concatenation of tags
      serially into long DNA molecules. SAGE is an innovative technique that offers the
      potential of cataloging both the identity and relative frequencies of mRNA
      transcripts in a given RNA preparation. It can quantify low-abundance transcripts
      and reliably detect relatively small differences in transcript abundance between
      cell populations. SAGE data can be used to complement studies in cases where
      other gene expression methods may be more convenient or efficient. SAGE can be
      used in a wide variety of applications to identify disease-related genes, to
      analyze the effect of drugs on tissues, and to provide insights into the disease
      pathways. The most important application of SAGE is the identification of
      differentially expressed genes. In this review, we describe various applications
      of this powerful technology in malarial parasite, yeast, plant, and animal
      systems.

PMID- 15240922
TI  - Serial Analysis of Gene Expression: Applications in Human Studies.
AB  - Serial analysis of gene expression (SAGE) is a powerful tool, which provides
      quantitative and comprehensive expression profile of genes in a given cell
      population. It works by isolating short fragments of genetic information from the
      expressed genes that are present in the cell being studied. These short
      sequences, called SAGE tags, are linked together for efficient sequencing. The
      frequency of each SAGE tag in the cloned multimers directly reflects the
      transcript abundance. Therefore, SAGE results in an accurate picture of gene
      expression at both the qualitative and the quantitative levels. It does not
      require a hybridization probe for each transcript and allows new genes to be
      discovered. This technique has been applied widely in human studies and various
      SAGE tags/SAGE libraries have been generated from different cells/tissues such as
      dendritic cells, lung fibroblast cells, oocytes, thyroid tissue, B-cell lymphoma,
      cultured keratinocytes, muscles, brain tissues, sciatic nerve, cultured Schwann
      cells, cord blood-derived mast cells, retina, macula, retinal pigment epithelial
      cells, skin cells, and so forth. In this review we present the updated
      information on the applications of SAGE technology mainly to human studies.

PMID- 15240923
TI  - Exercise training prevents and protects streptozotocin-induced oxidative stress
      and beta-cell damage in rat pancreas.
AB  - The aim of the present study was the evaluation of possible protective effects of
      exercise against beta-cell damage in streptozotocin (STZ)-induced diabetes in
      rats. The animals were divided into five groups: the control group, the STZ
      induced diabetes group, the STZ-induced diabetes and light-intensity exercise
      group, the STZ-induced diabetes and moderate-intensity exercise group, and the
      STZ-induced diabetes and heavy-intensity exercise group. Animals in the exercise
      groups were made to swim one of three exercise protocols once a day for 12
      consecutive weeks. STZ was injected intraperitoneally at a single dose of 50
      mg/kg for diabetes induction. Exercise training was continued for 4 weeks prior
      to STZ administration; these applications were continued end of the study (for 12
      weeks). Erythrocyte and pancreatic tissue malondialdehyde (MDA) levels and serum
      nitric oxide (NO) concentration were measured. Moreover glutathione peroxidase
      (GSHPx), superoxide dismutase (SOD) and catalase (CAT) were also measured in
      pancreatic homogenates. Pancreatic beta-cells were examined by
      immunohistochemical methods. STZ increased lipid peroxidation and decreased the
      antioxidant enzyme activity significantly. Exercise, especially moderate
      intensity exercise has shown protective effect probably through decreasing lipid
      peroxidation and increasing antioxidant enzyme activity. Islet cell degeneration
      and weak insulin immunohistochemical staining were observed in STZ induced
      diabetic rats. Increased intensity of staining for insulin and preservation of
      beta-cell numbers were apparent in the exercise-applied diabetic rats.
      Interestingly, the best result was obtained from moderate-intensity exercise.
      These findings suggest that exercise has a therapeutic and/or protective effect
      in diabetes by decreasing oxidative stress and preservation of pancreatic beta
      cell integrity.

PMID- 15240924
TI  - Detection of clone-specific immunoglobulin heavy chain genes in the bone marrow
      of B-cell-lineage lymphoma after treatment.
AB  - In order to determine the appropriate treatment of malignant lymphoma, it is
      important to know the degree to which extra-nodal invasion of lymphoma cells has
      occurred. We amplified complementarity-determining region (CDR) III genes in 64%
      of lymph node samples at the onset or relapse of B-cell-lineage non-Hodgkin's
      lymphoma (NHL) in 22 patients. By using a clone-specific CDR III probe in each
      patient, we were able to detect minimal residual disease (MRD) of lymphoma cells
      in the bone marrow and/or blood in 9 out of 14 cases (64.2%) at the onset of the
      disease or relapse, whereas abnormal cells in the bone marrow and/or blood were
      identified by routine morphological analysis in only 4 out of 22 cases (18.2%).
      This indicates that extranodal invasion of malignant cells may be common in
      patients with NHL. In some cases, the clone-specific CDR III gene was still
      expressed in the samples of bone marrow and/or peripheral blood even after
      chemotherapy, when other markers associated with NHL were no longer expressed.
      Five out of six cases in this group had a worse outcome associated with NHL. On
      the other hand, most of the cases whose clone-specific CDR III gene was no longer
      expressed in the bone marrow and/or in circulation after treatment had a
      relatively fair prognosis. These results indicate that the detection at molecular
      level of MRD in extranodal organs may prove useful as a predictor of prognosis
      for NHL.

PMID- 15240925
TI  - Comparison of magnetoencephalographic spikes with and without concurrent
      electroencephalographic spikes in extratemporal epilepsy.
AB  - Interictal spikes in patients with epilepsy may be detected by either
      electroencephalography (EEG) (E-spikes) or magnetoencephalography (MEG) (M
      spikes), or both MEG and EEG (E/M-spikes). Localization and amplitude were
      compared between E/M-spikes and M-spikes in 7 adult patients with extratemporal
      epilepsy to evaluate the clinical significance of MEG spikes. MEG and EEG were
      simultaneously measured using a helmet-shaped MEG system with planar-type
      gradiometers and scalp electrodes of the international 10-20 system. Sources of
      E/M-spikes and M-spikes were estimated by an equivalent current dipole (ECD)
      model for MEG at peak latency. Each subject showed 9 to 20 (mean 13.4) E/M-spikes
      and 9 to 31 (mean 16.3) M-spikes. No subjects showed significant differences in
      the ECD locations between E/M- and M-spikes. ECD moments of the E/M-spikes were
      significantly larger in 2 patients and not significantly different in the other 5
      patients. The similar localizations of E/M-spikes and M-spikes suggest that
      combination of MEG and EEG is useful to detect more interictal spikes in patients
      with extratemporal epilepsy. The smaller tendency of ECD amplitude of the M
      spikes than E/M-spikes suggests that scalp EEG may overlook small tangential
      spikes due to background brain noise. Localization value of M-spikes is
      clinically equivalent to that of E/M-spikes.

PMID- 15240926
TI  - Effects of desalted deep seawater on hematologic and blood chemical values in
      mice.
AB  - Various processed foods and beverages have been manufactured using deep seawater
      (DSW), desalted DSW (dDSW), and concentrated DSW in Japan. To confirm the safety
      of dDSW, we investigated hematologic and blood chemical effects of dDSW in mice.
      The dDSW and desalted surface seawater (dSSW) were diluted to 6.7%, 10%, and 20%
      with purified water. BALB/c mice were housed for 12 weeks, and administered the
      diluted dDSW, dSSW, or purified water as a control during the period. The results
      for dDSW were compared with those for dSSW and purified water. None of the groups
      of mice showed any clear abnormal growth or behavior; neither did any show signs
      of illness nor a single case of death during the 12 weeks study. We found no
      significant differences between the dDSW and control groups in terms of red blood
      cell count, hemoglobin, hematocrit, white blood cell count, and neutrophil
      counts, whereas white blood cell and lymphocyte counts were significantly higher
      in the 10% dSSW group at the end of 4 and 12 weeks than those in the control
      group. A significantly higher triglyceride level was detected only in the 6.7%
      dSSW group. Our results show no evidence of acute or subacute effects of diluted
      dDSW. Effects of diluted dDSW on hematologic and blood chemical values in mice
      are thought to be similar to those of purified water. This finding suggests that
      dDSW is as safe as purified water for drinking water.

PMID- 15240927
TI  - Serum osteocalcin levels in hyperthyroidism before and after antithyroid therapy.
AB  - Hyperthyroidism is characterized by accelerated bone turnover, caused from direct
      stimulation of bone cells by increased thyroid hormones. In this study, we aimed
      to investigate serum osteocalcin levels as a bone formation marker, before
      antithyroid (propylthiouracil) therapy at hyperthyroid stage and after
      antithyroid therapy at euthyroid stage of the patients. Twenty four hyperthyroid
      patients (18 females, 6 males) and 20 (13 females, 7 males) healthy controls were
      included into this study. Blood and urine samples were taken before medical
      treatment at hyperthyroid state, and after the antithyroid therapy until the
      patients reached the euthyroid state. Serum alkaline phosphatase, osteocalcin,
      calcium, phosphorus, Free T3, Free T4, TSH and urine calcium/creatinine levels
      were assessed. We found a significant decrease in serum osteocalcin (p=0.006),
      urinary calcium/creatinine (p=0.004), and serum phosphorus (p=0.038) levels in
      euthyroid state in comparison to hyperthyroid state. The increases in serum bone
      formation marker osteocalcin and bone resorption marker urinary
      calcium/creatinine levels in hyperthyroid state compared to euthyroid state in
      our study confirmed that hyperthyroid patients have high bone turnover. We
      conclude that, hyperthyroid patients has high bone turnover of formation and
      resorption even after attainment of euthyroidism. Osteocalcin and urine
      calcium/creatinine are sensitive markers in documenting bone remodeling during
      treatment of hyperthyroidism.

PMID- 15240928
TI  - Development of the Korean version of Short-Form 36-Item Health Survey: health
      related QOL of healthy elderly people and elderly patients in Korea.
AB  - The health-related QOL (HRQOL) has been used extensively in clinical and
      epidemiological research and health service studies. Especially, the Medical
      Outcome Study Short-form 36-Item Health Survey (SF-36) is a widely used health
      status measure. However, a Korean version has not been developed and tested yet.
      The purpose of this study was to develop a Korean version of the Short-form
      Health Survey (SF-36) for use in health related quality of life measurements for
      Korean elderly people. SF-36 data from 90 healthy elderly people using Social
      Education Service and 120 elderly patients using a day care service in Seoul,
      Korea, were examined. We translated SF-36 version 2.0 into Korean and assessed
      its reliability and validity. In the results, the content validity and
      discriminant validity were found to be satisfactory. Cronbach's alpha
      coefficients ranged from 0.9298 to 0.9383. The test-retest reliability
      coefficients ranged from 0.710 to 0.895. In addition, the utility was examined by
      testing the correlation between the health-related QOL and related factors (sex,
      age, motor function, ability of daily life) among the elderly people. The present
      findings suggested that the Korean version of SF-36 would be useful as a measure
      of the health related QOL in Korean elderly people.

PMID- 15240929
TI  - Stress perception and social indicators for low back, shoulder and joint pains in
      Japan: national surveys in 1995 and 2001.
AB  - This study aims to clarify the effects of stress perception and related social
      indicators on three major musculoskeletal symptoms: low back, shoulder, and joint
      pains in a Japanese population. Twenty health-related variables (stress
      perception and 19 social indicators) and the three symptoms were obtained from
      the following Japanese national surveys: the Comprehensive Survey of Living
      Condition of the People on Health and Welfare, the System of Social and
      Demographic Statistics of Japan, and the Statistical Report on Health
      Administration Services. The results were compared among 46 Japanese prefectures
      in 1995 and 2001. By factor analysis, the 19 indicators were classified into
      three factors of urbanization, aging and life-regularity, and individualization.
      The prevalence of stress perception was significantly correlated to the 8
      indicators of urbanization factor. Although simple correlation analysis revealed
      a significant relationship of stress perception only to shoulder pain (in both
      years) and low back pain (in 2001), the results of multiple regression analysis
      showed that stress perception and some urbanization factors were significantly
      associated with all the three symptoms in both years exclusive of joint pain in
      1995. Taking the effects of urbanization into consideration, stress perception
      seems to be closely related to the complaints of musculoskeletal symptoms in
      Japan.

PMID- 15240930
TI  - Weekly paclitaxel in pretreated metastatic breast cancer: retrospective analysis
      of 52 patients.
AB  - Single-agent paclitaxel has been shown to be effective as both first- and second
      line treatment of metastatic breast cancer, and the efficacy and tolerability of
      weekly administration of paclitaxel has generated much interest. Fifty-two
      patients with pretreated metastatic breast cancer who were admitted to Hacettepe
      University between January 2001 and June 2002 were retrospectively analyzed in
      this study. Paclitaxel was administered weekly in a dose of 80 mg/m(2) over 1
      hour. The median number of cycles delivered was 20 weeks (range, 8 to 24). The
      median delivered dose was 2400 mg (range, 960 to 3840 mg). At a median follow-up
      of 12.3 months (range, 6 to 17), all patients were assessable for response and
      toxicity. A complete response and partial response were observed in 7 (13.5%),
      and 19 (36.5%) patients, respectively. Overall response rate was 50%. Median
      duration of response was 10 months (range, 3 to 16). Therapy was generally well
      tolerated, and toxicities were manageable. Severe leukopenia was seen in two (4%)
      patients. Based on these results, we conclude that weekly paclitaxel is a well
      tolerated and highly effective regimen in pre-treated metastatic breast cancer.

PMID- 15240931
TI  - Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes
      mellitus.
AB  - We investigated lipid peroxidation, resistance of plasma and red blood cells to
      oxidation, and antioxidant defense system in erythrocytes and sera in patients
      with type 2 diabetes mellitus. One group included newly diagnosed 20 patients and
      the other included 20 patients treated with oral antidiabetic agents (OAD).
      Twenty healthy subjects served as controls. Serum and red blood cell
      malondialdehyde (MDA), glutathione (GSH), resistance to oxidation, and plasma
      thiol (total -SH) levels were measured. In addition, glycated hemoglobin, serum
      fructosamine, uric acid, total protein, total cholesterol, triglyceride and
      glucose levels were determined. Although newly diagnosed patients had higher
      serum and erythrocyte MDA levels than those of controls, the highest levels of
      MDA were determined in patients treated with OAD. MDA levels after exposing to
      oxidation increased in OAD group more than in newly diagnosed patients. Total -SH
      and erythrocyte GSH levels of the both diabetic groups were lower than controls.
      These results show that serum and erythrocyte lipid peroxidation was increased in
      diabetic patients. The sera of the patients showed a decreased resistance against
      oxidation. We therefore suggest that the effect of increased free radicals may be
      prevented by antioxidant systems in early stages of type 2 diabetes but in
      advanced stages this relationship is impaired owing to decreased antioxidant
      activity. Decreased red blood cell GSH and serum total -SH levels may be due to a
      compensation mechanism of the antioxidants.

PMID- 15240932
TI  - The role of gamma-aminobutyric acid and glutamate for hypoxic ventilatory
      response in anesthetized rabbits.
AB  - Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained,
      the initial increase in ventilation is followed by a decrease in ventilation.
      Hypoxia causes changes in brain neurotransmitters depending on its severity and
      durations. The purpose of this study was to investigate the role of gamma
      aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in
      rabbits. The experiments were performed in peripheral chemoreceptors intact and
      denervated rabbits anesthetized with Na-pentobarbitate. For
      intracerebroventricular (ICV) injections of reagents in each animal, cannula was
      placed in left lateral cerebral ventricle by stereotaxic method. After ICV
      injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression
      of respiratory activity. On the other hand, after ICV injection of GABA,
      breathing of hypoxic gas mixture (8% O(2)-92% N(2)) in both groups produced the
      hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA(A)
      receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic
      hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate
      NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic
      hyperventilation observed while the animals were breathing hypoxic gas mixture.
      Our findings suggest that ICV injection of GABA causes respiratory depression in
      normoxic conditions, and that it increases ventilation in hypoxic conditions with
      or without peripheral chemoreceptor impulses by increasing glutamate.

PMID- 15240933
TI  - Age-related changes of bone mineral density and microarchitecture in miniature
      pigs.
AB  - Bone mineral density (BMD), distribution of its density and bone
      histomorphometric parameters were evaluated in lumbar vertebra of normally
      growing miniature pigs. The fourth lumbar vertebra (L4) of the Gottingen
      miniature pig were used in this cross-sectional study in vitro. The BMD of the
      miniature pig was similar to that of humans in tendency of gender differences and
      some growth patterns during puberty. In these regards this animal appears useful
      as a model for human bone study. However, the trabecular and cortical BMDs of
      lumbar spine were extremely high value (399.43 +/- 26.36 mg/cm(3) in female
      trabeculae; 973.06 +/- 69.55 mg/cm(3) in female cortical bone; 419.04 +/- 34.84
      mg/cm(3) in male trabeculae; 1038.81 +/- 125.72 mg/cm(3) in male cortical bone in
      pigs 30 months or more). Furthermore, histomorphometric analysis yielded values
      that were remarkably different from those found in humans. From these results, it
      was revealed that miniature pig had a higher bone mass and denser trabecular
      network than human, indicating that its bone is probably stronger. Therefore,
      care should be taken in choosing the miniature pig as a bone study model.

PMID- 15240934
TI  - CTLA-4 recombinant protein genetically fused to canine Fcepsilon receptor Ialpha
      enhances allergen specific lymphocyte responses in experimentally sensitized
      dogs.
AB  - Vaccination with a recombinant antigen fused to a targeting molecule is a
      potential strategy for inducing efficient immune responses. For the therapeutic
      purpose of allergic diseases in dogs, a DNA construct which expresses recombinant
      fusion protein with two functional domains, cytotoxic T lymphocyte antigen (CTLA
      4) and Fcepsilon receptor Ialpha, was developed to bridge antigen-presenting
      cells and IgE-allergen complex. The recombinant fusion protein expressed by the
      DNA construct was demonstrated to retain the ability to bind monocytes in PBMC
      and dog IgE, respectively. Additionally, the recombinant protein induced
      enhancement of allergen-induced lymphoproliferation in experimentally sensitized
      dogs under conditions of suboptimal allergen stimulation. These results indicated
      that the DNA construct could enhance allergen-induced immune responses in vivo,
      implying its usefulness for perspective application in immunotherapy in dogs.

PMID- 15240935
TI  - The detection of bovine lactoferrin binding protein on Trypanosoma brucei.
AB  - Trypanosoma brucei, the causative agent of sleeping sickness in humans, requires
      transferrin (TF) for growth. Therefore, T. brucei has a TF receptor that allows
      it to obtain iron from TF. Lactoferrin (LF), a member of the TF family protein,
      is an iron-binding protein that is found in most biological fluids of mammals. LF
      has been shown to interact with some bacteria species by specific receptor-ligand
      binding. We examined the ability of T. brucei to bind bovine LF (bLF) by using a
      fluorescence test, streptavidin-biotin (SAB) microplate analysis, and far Western
      blotting using a biotin-streptavidin system. We found that bLF bound to
      components of T. brucei, and that bLF hydrolysate disrupted the sites responsible
      for binding to parasite proteins. Furthermore, bLF, human LF, bovine TF, and
      ovotransferrin bound same proteins of T. brucei, which exhibited molecular masses
      of 40 and 43 kDa. The N-terminal amino acid sequence of the 40 kDa bLF binding
      protein was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

PMID- 15240936
TI  - Digestibility of soybean and pigeon pea seed meals and morphological intestinal
      alterations in pigs.
AB  - To compare the nutrient digestibility of soybean meal (SM) and pigeon pea seed
      meal (PM) as well as morphological intestinal alterations in piglets fed them,
      three pigs per group were randomly selected at the end of the feeding experiment
      for ten days. Growth performance was higher in the SM group than in the PM group
      (p<0.05). The digestibility of crude protein, crude fat and crude fiber was
      80.6%, 23.6% and 52.4% in the SM group, while in the PM group, values of 49.8%,
      23.6% and 43.2% were observed, respectively. Digestible energy was 3.26 kcal g(
      1) in SM and 3.17 kcal g(-1) in PM. It was concluded that the digestibility of PM
      was lower than that of SM; almost half of the protein in PM was digested. Dietary
      treatments had no effect on length of each small intestinal segment and weight of
      visceral organs (small intestine, liver, heart, spleen, kidney, stomach and lung)
      except the decreased kidney weight in the PM group (p<0.05). The epithelial cells
      on the jejunal villi showed a dome-like shape in the SM group, but they were a
      flat shape in the PM group. The present digestion trial and histological
      intestinal data suggest that the intestinal digestive and absorptive functions
      are much more atrophied in the PM group than in the SM group, and demonstrate
      that histological intestinal alterations might be well related with the
      intestinal functions.

PMID- 15240937
TI  - Study of migration of neural crest cells to adrenal medulla by three-dimensional
      reconstruction.
AB  - Adrenal medullary cells are derived from the neural crest. To study the formation
      process of the adrenal medulla in the embryonic period, we visualized chromaffin
      cells of rat embryos at 13 to 17 days of gestation using anti-tyrosine
      hydroxylase (TH) antiserum, and created three-dimensional images from serial
      tissue sections. Between 13 and 15 days of gestation, TH-positive cells
      (chromaffin cells) migrated from a group of TH-positive cells present dorsal to
      the adrenal primordium via the medial cranial end of the adrenal primordium into
      the adrenal primordium. At or after 16 days of gestation, the adrenal capsule was
      formed except on the ventral aspect of the cranial end of the adrenal gland, from
      which TH-positive cells penetrated into the adrenal gland. The reconstructed
      images showed that TH-positive cells were present contiguously from the
      sympathetic chain ganglia through a group of TH-positive cells ventral to the
      adrenal gland into the adrenal cortex, and that the group of TH-positive cells
      ventral to the adrenal gland communicated with the preaortic ganglion present
      ventral and caudal to the adrenal gland. These results suggest that neural crest
      cells use the same pathway to migrate to the sympathetic chain ganglia dorsal to
      the adrenal gland, to the adrenal gland, and to the preaortic ganglion.

PMID- 15240938
TI  - Molecular cloning and characterization of chicken tumor necrosis factor (TNF)
      superfamily ligands, CD30L and TNF-related apoptosis inducing ligand (TRAIL).
AB  - CD30 ligand (CD30L) and tumor necrosis factor (TNF)-related apoptosis inducing
      ligand (TRAIL) are members of the TNF-superfamily that have many important
      biological activities in cell proliferation and apoptotic death. In this study,
      both genes in the chicken were cloned and their expression was analyzed.
      Complementary DNA fragments were obtained from a suppressive subtractive
      hybridization library with or without lipopolysaccharide (LPS)-stimulation.
      Chicken CD30L consists of 1,152 base pairs (bp) with an open reading frame (ORF)
      of 720 bp having 36.4% identity with human CD30L, whereas chicken TRAIL is 1,134
      bp long with an ORF of 912 bp having 54.4% identity with human TRAIL. Chicken
      CD30L was expressed at high levels in the spleen, bursa of Fabricius and in the
      chicken monocytic leukemia cell line, IN24. Stimulation with LPS in the spleen,
      bursa of Fabricius and the IN24 cell line did not affect CD30L expression. The
      gene expression of chicken TRAIL was essentially to the same level in all tissues
      examined. The time course of expression was not significantly altered by LPS
      stimulation in the spleen, thymus and bursa of Fabricius, but reached a maximal
      level 8 hr after stimulation in the IN24 cell line. The high level expression of
      both genes in lymphoid organs and IN24 cell line indicates that chicken CD30L and
      TRAIL may also play an important role in apoptotic signal transduction and the
      regulation of cell proliferation in the immune system.

PMID- 15240939
TI  - Expression of a tumor-associated antigen, RCAS1, in canine mammary tumors.
AB  - Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), one of novel
      cancer cell-surface antigens, is strongly expressed in invasive cancers. RCAS1
      inhibits the in vitro growth of lymphocytes such as T cells and natural killer
      (NK) cells, and induces apoptotic cell death. We investigated the expression of
      RCAS1 in canine mammary tumor cell lines and tumor cells by immunohistochemistry,
      and also in situ deoxyribonucleic acid (DNA) fragmentation in tumor-infiltrating
      lymphocytes (TILs) by the terminal deoxynucleotidyl transferase mediated
      deoxyuridine triphosphate nick end labeling (TUNEL) method. All canine mammary
      tumor cell lines expressed RCAS1 at both the messenger ribonucleic acid (mRNA)
      and protein level. Immunohistochemically, RCAS1 was negative in 100% of normal
      mammary glands, but was expressed in 100% of malignant tumors examined. In most
      malignant mammary tumors, RCAS1 was localized in the cytoplasm with no polarity
      of expression. In benign mammary tumors, it was detected on the luminal surface
      of the tumor cell. RCAS1 expression or localization was significantly correlated
      with malignancy. In situ DNA fragmentation of CD3-positive TILs was observed in
      RCAS1-expressing tumors. RCAS1-expressing tumors, indicating a possible induction
      of apoptotic cell death in TILs through RCAS1 expression. These observations
      suggest that RCAS1 probably plays an important role in tumor progression and
      escape from immune surveillance in canine mammary tumors.

PMID- 15240940
TI  - The reference values of the T-wave of the patellar tendon reflex in normal dogs.
AB  - The T-wave of the patellar tendon reflex (PTR) was recorded in 24 neurologically
      normal dogs. The surface electromyogram (EMG) was recorded as the T-wave from the
      vastus lateralis muscle (VL) in response to percussion of the patellar tendon.
      The distance of the reflex arc (DRA) was measured along the straight line between
      the spinous process of L5 and the greater trochanter (GT), and between GT and the
      patellar ligament (PL). There was a significant correlation (P<0.001) of the
      latency with the DRA on each side, but no difference in the slopes of the
      relationships between right and left VL was shown. The regression line between
      the DRA and the latency of all data was Y = 0.0216X + 1.693, where Y = latency in
      ms, X = DRA in mm. The mixed sensory-motor conduction velocity was estimated as
      84.6 +/- 5.5 m/s. In contrast, there was no significant correlation between the
      DRA and the amplitude of the T-waves. The mean (mean-CV) and standard deviation
      (SD-CV) of all CV (coefficient of variation) in each dog were 9.14 +/- 3.65% in
      latency and 3.54 +/- 1.14% in amplitude, indicating that the use of a simple hand
      held reflex hammer is sufficient to record the reproducible T-wave of the PTR
      even in unanesthetized dogs. This method was applied to a case with minimal
      paraparesis, and the latency of the T-wave of the PTR in the right hind limb with
      slight proprioceptive deficit was outside of the upper limit of the 95%
      confidence interval between latency and the DRA. In conclusion, this method may
      be used in neurological diagnosis to quantify more precisely the PTR in dogs.

PMID- 15240941
TI  - Dental incremental lines in Sika deer (Cervus nippon); polarized light and
      fluorescence microscopy of ground sections.
AB  - Periodic growth incremental lines are found universally in dental hard tissues.
      This periodicity theoretically allows for estimation of age, even in days, which
      would be useful in studies of wild animals. In the present study, enamel and
      dentin increments of the sika deer (Cervus nippon) were observed in ground
      sections with a polarized light microscope, and their periodicity was examined by
      the use of a chronological labeling method with fluorochromes. Enamel increments
      occurred at a mean interval of 10.6 (SD=1.5) microm, and mean spacing of dentin
      increments was 17.3 (SD=1.8) microm. Fluorochromic marking revealed that
      incremental lines form each day in enamel and almost every second day in dentin.
      The fluorescence-labeled lines suggest that enamel formation of the first molar
      is complete by the age of 5 months. Due to its longer interval of incremental
      lines and longer term of formation, we conclude that dentin is more suitable than
      enamel for day-age estimation in sika deer. Experimental confirmation of
      incremental growth periodicity in various species can improve the reliability of
      use of tooth increments for age estimation and life history reconstruction.

PMID- 15240942
TI  - Distributive and phagocytic characteristics of hepatic macrophages in five
      cetaceans belonging to Delphinidae and Ziphiidae.
AB  - Details of morphology and distribution of hepatic macrophages in cetaceans were
      investigated using the immunohistochemistry with an antibody (SRA-E5) generated
      against human macrophage scavenger receptor antigen. Liver samples were obtained
      from five species of cetaceans (Baird's beaked whales, short-finned pilot whales,
      Risso's dolphins, bottlenose dolphins, and pantropical spotted dolphins). Except
      for two species of whales, the number of SRA-E5-positive Kupffer cells was
      greatest in the perivenous zone (zone 3), followed by the mid-zonal (zone 2) and
      periportal (zone 1) zones; this distribution pattern was different from that in
      cattle examined here and previously reported rodents with the highest number in
      zone 1. The frequency of Kupffer cell in each of zones was significantly
      different among species, and interestingly, the total mean of the Kupffer cell
      number in three zones increased as the body-length of species was small. In
      cetaceans, Kupffer cells in zone 1 appeared larger and more stellate in shape,
      whereas those in zone 3 were smaller and rounder. All cetaceans but Baird's
      beaked whales had the black pigment-containing Kupffer cells, with the greatest
      number in zone 3, and macrophages with the similar pigments were also seen in the
      hepatic intermediate septa, indicating an active phagocytosis. Most of the black
      pigments were considered to be lipofuscin and such pigments were not seen in the
      bovine livers. These results indicate that cetacean hepatic macrophages show
      differences in the distribution and phagocytosis among hepatic lobular zones, or
      between cetacean species and terrestrial animals.

PMID- 15240943
TI  - Developmental expression of p63 in the mouse testis.
AB  - p63 is a member of the p53 gene family and have structural similarities with p53.
      p63 encodes for multiple isotypes either with N-terminal transactivation domain
      (TAp63) or without it (DeltaNp63). In the mammalian testis, it has been shown
      that p53 plays important roles in the regulation of germ cell apoptosis and
      meiosis. However, little is known for the physiological function of p63 in the
      mammalian spermatogenesis. To investigate the potential roles of p63 in the
      developing mouse testis, we examined the expression pattern of p63 in the mouse
      testis from birth to adulthood. In addition to the TAp63 mRNA which was
      continuously expressed in the developing testis, transcripts encoding DeltaNp63
      was detected at specific stages of testicular development by RT-PCR, from
      postnatal day 1 to day 7 and from 3 weeks to 4 weeks after birth. Western blot
      analysis of whole testis lysates with anti-p63 antibody revealed an approximately
      68 kD band throughout development and a less abundant protein at 60 kD in the
      earlier period of postnatal development. Immunopositive reactions for p63 were
      observed as early as 10 days after birth and p63 protein was localized to the
      nuclei of spermatocytes and round spermatids. These findings strongly suggest
      that p63 might be involved in the regulation of proliferation and differentiation
      of spermatogenic cells in the developing mouse testis.

PMID- 15240944
TI  - Cellular kinetics of villous epithelial cells and m cells in rabbit small
      intestine.
AB  - The cellular kinetics of villous columnar epithelial cells and M cells in the
      rabbit small intestine were determined by the use of 5-bromo-2'-deoxyuridine
      (BrdU) as a tracer. To identify M cells, vimentin antibody was used. The BrdU
      labeled nuclei of columnar epithelial cells reached the base of intestinal villi
      in all portions at 1 day after BrdU administration. Thereafter, BrdU-labeled
      cells migrated toward the villous tip, but they did not move at a uniform speed.
      The epithelial cells which existed in intestinal villi on circular folds moved
      faster than those on mucosa other than circular folds. At 7 days after BrdU
      administration, the leading edge of BrdU-labeled epithelial cells already
      disappeared from the villous tip in all portions of the small intestine. In the
      ileal Peyer's patch, the BrdU-labeled nuclei of microvillous epithelial cells and
      vimentin-positive M cells appeared near the intestinal crypt orifice at 1 day
      after BrdU administration, and then migrated toward the luminal surface of the
      follicle-associated epithelium (FAE). As they moved toward the upper portion of
      FAE, the number of BrdU-labeled M cells on the side of the dome decreased
      simultaneously. The leading edge of BrdU-labeled epithelial cells disappeared
      from the top of the FAE within 7 days. These results suggest that M cells may
      differentiate from the undifferentiated cells in intestinal crypts within 1 day
      and disappear from the top of the FAE after the change of their form from M cells
      into microvillous epithelial cells.

PMID- 15240945
TI  - Distribution of the pores of epithelial basement membrane in the rat small
      intestine.
AB  - The distribution and diameter of the pores of epithelial basement membrane in the
      intestinal villi and the lymph nodules of ileal Peyer's patches were investigated
      in the rat small intestine by scanning electron microscopy after the removal of
      the overlying epithelial cells with OsO(4) maceration. In the duodenum, jejunum
      and ileum, the pores were mainly distributed at the upper three fourths of the
      villi, but were scarce around the top of the villi. The diameter of some of the
      pores in the upper three fourths of the villi was larger than that of those in
      the lower portion. The protrusion of lymphocytes and the cytoplasmic processes of
      macrophages were also seen at the orifices of the pores. In ileal Peyer's
      patches, in contrast, pores were densely distributed in the lower one third of
      the follicle-associated epithelium (FAE) where M cells were mainly seen.
      Furthermore, these pores were larger than those found in the upper two thirds.
      Lymphocytes or cytoplasmic processes of macrophages were frequently seen in the
      lower one third of FAE. These results suggest that the pores at the basement
      membrane correspond to the passage of the immunocompetent cells which are in
      contact with M cells or villous columnar epithelial cells and that the abundance
      of pores is a sign of aggressive interaction between the particular epithelial
      cells and the immunocompetent cells at the upper three fourths of intestinal
      villi and the lower one third of FAE in the rat small intestine.

PMID- 15240946
TI  - A suspected case of ornithine transcarbamylase deficiency in a cat.
AB  - An 18 month-old, intact female American Shorthair cat was presented for
      evaluation of stunted growth and postprandial depression. Fasting serum ammonia
      and serum bile acid concentrations were above reference ranges at 396 microg/dl
      and 6.5 micromol/ l and their postprandial concentrations were 785 microg/dl and
      9.5 micromol/l, respectively. The initial tentative diagnosis of a portosystemic
      shunt was excluded by mesenteric portography and histopathology of the liver. The
      cat was then suspected of a urea cycle enzyme deficiency and its urine was
      analyzed by gas chromatography-mass spectrometry. A presumptive diagnosis of
      ornithine transcarbamylase deficiency was made on the basis of the detection of
      orotic acid and uracil.

PMID- 15240947
TI  - The effects of microwave-irradiated fixation for postmortem changes of the
      kidney.
AB  - In the present study, we evaluated the advantages of microwave-irradiated
      fixation for postmortem autolysis of the kidney. Mouse kidneys, sampled at 0, 1,
      3, 5, 10, 15, 20 and 25 hr after death, were fixed with 10% neutral formalin by
      microwave irradiation (MWI; 20 sec/500 W) and by conventional immersion. They
      were then examined with light and electron microscopy, morphometrics and
      immunohistochemicals. Light microscopic and morphometric observations showed that
      structural preservation effect of MWI was limited to the proximal convoluted
      tubules at 25 hr. Contrary, mild ultrastructural damage by MWI was found in the
      glomeruli at 0 and 15 hr. Immunohistochemistry for renin and alpha-smooth muscle
      actin showed no apparent differences between MWI and the immersion.

PMID- 15240948
TI  - Molecular cloning of canine Mcl-1 gene and its expression in tumor cell lines.
AB  - The canine Mcl-1 gene was cloned and sequenced. Canine Mcl-1 clone was 2694 base
      pairs in length and encoded 350 amino acids. The predicted amino acid sequence
      was 87.7%, 77.1% and 75.7% homologous to predicted human, mouse and rat Mcl-1,
      respectively. RT-PCR analysis revealed that canine Mcl-1 mRNA was expressed in
      PBMCs (peripheral blood mononuclear cells), bone marrow cells, MDCK (Madin-Darby
      canine kidney) and GL-1 (canine B cell leukemia) whereas undetectable in CL-1
      (canine T cell lymphoma) cell line.

PMID- 15240949
TI  - Thymoma in a dog with a part of granular cell proliferation and concurrent
      lymphoma cells.
AB  - A 12-year-old male Shiba dog showed anemia and the swelling of systemic lymph
      nodes. X-ray and post mortal examinations revealed a anterior mediastinal mass.
      Histologically, the tumor mass consisted of four different elements; cord-like
      proliferation of cuboidal epithelial cells, tubular or cystic structures lined
      with ciliated epithelial cells, proliferation of large round-shaped epithelial
      cells with PAS-slightly positive granular cytoplasm, and diffuse proliferation of
      neoplastic lymphocytes. Epithelial cells in cord-like or cystic structures were
      strongly positive for cytokeratin. Granular or foamy cells were negative for all
      markers examined and had myelin-like bodies in the cytoplasm by electron
      microscopy. The neoplastic lymphocytes in the tumor mass were considered being
      derived from concurrent multicentric lymphoma. Based on these findings, the
      present case was diagnosed as thymoma with a part of granular cell proliferation
      and concurrent lymphoma cells.

PMID- 15240950
TI  - Sequence comparison of the ORF 7 region of transmissible gastroenteritis viruses
      isolated in Japan.
AB  - The 3' end region nucleotide sequence, including ORF7, of nine Japanese and two
      U.S.A. isolates of transmissible gastroenteritis virus (TGEV) were determined and
      compared. Nine Japanese TGEV strains have been isolated over the past 40 years
      (1956-1997). From the comparison of determined nucleotide sequences, we could
      divide the TGEV Japanese isolates into two groups and distinguish them from TGEV
      U.S.A. isolates.

PMID- 15240951
TI  - High level activity of 2', 5'-oligoadenylate synthetase in dog serum.
AB  - Most animal cells that are exposed to interferon (IFN) experience an increase in
      the activity of 2', 5'-oligoadenylate synthetase (OAS), which is an important
      effector of IFN's antiviral action. OAS activity has been widely used in clinical
      chemistry as an indicator of IFN activity. In this study, we found that OAS
      activity in canine serum is 46.0 +/- 40.4 nmol/dl/hr, which is 10- to 100-fold
      higher than in other animals such as the cat (1.9 +/- 2.1), rabbit (4.0 +/- 1.1),
      and guinea pig (0.3 +/- 0.6). The canine OAS protein was detected by Western
      blotting using a 68M-10 monoclonal anti-murine OAS antibody, and was found to be
      composed of at least three distinct molecular species of p40 class OAS. Among
      these, the 40 and 42 kDa components were determined to be the major species in
      serum and fibroblast cell lines, respectively.

PMID- 15240952
TI  - Cloning of cDNAs encoding multiple subtypes of feline interferon-alpha from the
      feline epitherial cell line.
AB  - Mammalian interferon (IFN)-alpha consists of a 23-amino acid signal peptide and a
      166-amino acid mature protein. Feline (Fe) IFN-alpha has an extra unique molecule
      consisting of a 171-amino acid mature protein with a 5-amino acid insertion. We
      cloned eight new subtypes of cDNA encoding FeIFN- alpha from a feline epithelial
      cell line. Among all the FeIFN-alpha subtypes, including six that have previously
      been reported, the variations were found to be far less than those of IFN-alphas
      of other animals.

PMID- 15240953
TI  - Automated ribotyping, a rapid typing method for analysis of Erysipelothrix spp.
      strains.
AB  - Automated ribotyping classified 70 Erysipelothrix species strains, previously
      classified into 14 RAPD patterns and into 63 PFGE patterns, into 27 ribogroups.
      Twenty-three strains of the 70 analyzed and classified into 13 ribogroups were
      previously classified into six ribotypes by the traditional ribotyping method.
      Moreover, automated ribotyping differentiated seven strains that were not
      differentiated by PFGE. Therefore, automated ribotyping was more sensitive than
      RAPD and traditional ribotyping, and it might be a useful method for a rapid
      screening in epidemiological study of strains of this genus, and more accurate
      results can be obtained when this method is used together with PFGE.

PMID- 15240954
TI  - Enzyme-linked immunosorbent assay to detect Lawsonia intracellularis in rabbits
      with proliferative enteropathy.
AB  - Lawsonia intracellularis is an obligate intracellular pathogenic bacterium that
      causes proliferative enteropathy in domestic and experimental animals. Antiserum
      against synthetic peptides of the Lawsonia surface antigen (LsaA) well recognized
      L. intracellularis in infected ileum by immunohistochemistry. The synthetic
      peptides in LsaA showed strong reaction with serum from rabbits infected with L.
      intracellularis by enzyme-linked immunosorbent assay. These results suggest that
      ELISA used synthetic peptides in LsaA and anti-LsaA serum might be useful to
      diagnose for proliferative enteropathy.

PMID- 15240955
TI  - Molecular cloning of canine activation-induced cytidine deaminase (AID) cDNA and
      its expression in normal tissues.
AB  - Activation-induced cytidine deaminase (AID) is essential for class switch
      recombination, somatic hypermutation, and gene conversion of immunoglobulin gene.
      In the present study, canine AID cDNA was cloned from the lymph node of a healthy
      dog by RT-PCR with rapid amplification of cDNA ends (RACE) method. The canine AID
      cDNA was 1,377 bp in length, and contained the entire open reading frame encoding
      198 amino acids which had 94.9%, 94.4%, and 89.9% homology with human, mouse, and
      chicken homologues, respectively. Canine AID mRNA was expressed in thymus, lung,
      spleen, kidney, small intestine, lymph node, and tonsil of a healthy dog, similar
      to humans.

PMID- 15240956
TI  - Isolation of Rhodococcus equi from the feces of indigenous animals and soil from
      the Lower Zambezi National Park and Lochinvar National Park, Zambia.
AB  - Rhodococcus equi is an important pathogen in foals; however, its incidence in
      African indigenous animals is poorly understood. Fecal samples (92 from nine
      indigenous species) and 43 soil samples were collected from two Zambian National
      Parks. The presence of R. equi was investigated and 533 isolates were tested for
      the presence of 15- to 17-kDa antigens (VapA) and a 20-kDa antigen (VapB) by
      immunoblotting and PCR. R. equi was isolated (10(2)-10(4) colony forming units/g)
      from 75% of fecal and 74% of soil samples. Neither antigen was detected; however,
      about 20% of the isolates contained cryptic plasmids of various sizes. There was
      no evidence of virulent R. equi, but the avirulent form was widespread in the
      animals and the soil.

PMID- 15240957
TI  - Myocardial and peripheral concentrations of beta-endorphin before and following
      myocardial ischemia and reperfusion during coronary angioplasty.
AB  - There is substantial evidence indicating that endogenous opioid peptides are
      involved in the pathophysiology of myocardial ischemia and reperfusion. We
      measured the myocardial and peripheral concentrations of beta-endorphin before
      and following myocardial ischemia and reperfusion during coronary angioplasty.
      The results indicate that in patients with coronary artery disease, there was an
      augmented myocardial concentration of beta-endorphin. Moreover, there was an
      increased peripheral concentration of beta-endorphin following myocardial
      ischemia and reperfusion. The data support the previous notion that endogenous
      opioid peptides are involved in the pathophysiology of ischemic heart disease.

PMID- 15240958
TI  - The relationship between terminal QRS complex distortion and early low dose
      dobutamine stress echocardiography in acute anterior myocardial infarction.
AB  - Although the damage in myocardial infarction has been demonstrated to be related
      with the magnitude and number of ST elevation, its relation with terminal
      distortion of QRS is unclear. The relationship between terminal QRS distortion in
      ECGs on admission and the results of early low dose dobutamine stress
      echocardiography (LDSE) performed 6 +/- 2 days later was investigated. Patients
      admitted to our clinic within the first six hours of their chest pain and without
      a prior infarction diagnosis were divided into two groups based on the admission
      electrocardiogram as the absence (QRS-, n = 33) or presence (QRS+, n = 29) of
      distortion of the terminal portion of the QRS in > or = 2 leads (QRS+; J point at
      > 50% of the R wave amplitude in lateral leads or presence of ST elevation
      without S wave in leads V1-V3). There were no significant differences between the
      groups with respect to thrombolytic therapy or reperfusion criteria. During LDSE,
      the infarct zone wall motion score index (WMSI) in the QRS- group was
      significantly decreased relative to baseline (from 2.93 +/- 0.65 to 2.37 +/-
      0.84, P = 0.02), and it was significantly different compared with WMSI in the
      QRS+ group (P = 0.005). Improvement of akinetic regions to hypokinetic regions in
      the infarct zone (IZ) was found to be 33.5% (44/131) in the QRS- group and 17.8%
      (27/151 P = 0.004) in the QRS+ group. Furthermore, 55.1% (10/29) of the patients
      in the QRS+ group and only 18.1% (6/33) of those in the QRS- group did not
      respond to LDSE (P < 0.05). In multiple logistic regression analysis, while there
      was no relationship between good left ventricular functions (WMSI < 2) and
      terminal QRS distortion under basal conditions (P = 0.07), an independent
      relation was observed to exist between them after LDSE (P = 0.03, OR 4.48, 95%
      CI, 1.13-17.7). Moreover, plasma CK levels were higher in the QRS+ group (P =
      0.03), whereas the ejection fraction was worse (P = 0.01). In both groups, there
      was no correlation between the Selvester score and left ventricle WMSI at
      baseline, but this correlation was significantly improved with LDSE (QRS-; r =
      0.39 P = 0.02 and QRS+; r = 0.44 P = 0.01) The viability in the IZ is relatively
      less in those patients with terminal QRS distortion observed in their ECG on
      admission. This simple classification would be useful in predicting left
      ventricular function at the time of discharge.

PMID- 15240959
TI  - Do indices of coronary conductance after reperfusion reflect the extent of
      salvaged myocardium?
AB  - Existing indices of coronary conductance (hyperemic flow-versus-pressure slope
      index, FPSI, and zero flow pressure, Pzf) have been developed as measures of
      microcoronary resistance. These indices, however, refer to cases of normal
      hearts, and there are no reports studying these indices following acute
      myocardial infarction. In this study, we investigated whether FPSI and Pzf truly
      measure the extent of myocardial salvage after successful reperfusion therapy. We
      also developed a new index of zero pressure flow, Fzp. Nineteen patients who
      underwent successful reperfusion therapy to the proximal portion of the left
      anterior descending artery (LAD) were studied. After successful reperfusion
      therapy, a Doppler wire was placed into the LAD. Aortic pressure was recorded in
      real time. Results from the aortic pressure and flow meter were combined to
      produce FPSI, Pzf, and Fzp. All cases underwent a resting thallium (Tl) and BMIPP
      scintigram within five days of successful reperfusion therapy. Infarcted
      myocardium was estimated using a severity score calculated from the Tl
      scintigraphy (TlSS), and the BMIPP (BMIPPSS) was estimated using a severity
      score. Patients with a TlSS/BMIPPSS ratio of less than 0.4 were assigned to the
      successful salvage group (group S), while the others were assigned to the failed
      salvage group (group F). FPSI of group F was 1.91 +/- 0.26 m/sec and of group S
      was 0.92 +/- 0.43 m/sec (P < 0.01). Pzf of group F was 51 +/- 3 mmHg and of group
      S was 51 +/- 5 mmHg (NS). Fzp of group F was -98 +/- 16 cm/sec and of group S was
      -46 +/- 4 cm/sec (P < 0.05). FPSI and the new index of Fzp were useful in
      estimating the extent of myocardial salvage. Our results suggest that the Pzf
      index could not differentiate between the two groups.

PMID- 15240960
TI  - Relation between serum lipoprotein (a) and residual lesion stenosis of coronary
      artery after myocardial Infarction without reperfusion therapy.
AB  - Lipoprotein (a) (Lp(a)) is an independent risk factor for myocardial infarction
      (MI). It may also inhibit the fibrinolysis system, and Lp (a) affects the natural
      course of MI and the results of thrombolytic therapy. The purpose of this study
      was to investigate the influence of Lp (a) on the residual lesion stenosis of the
      infarction-related arteries (residual stenosis) in acute MI patients in whom
      reperfusion therapy was not performed. We studied 129 MI patients not given
      reperfusion therapy who underwent coronary angiography in the chronic stage.
      Morning fasting blood was collected and Lp (a), blood sugar, total cholesterol
      (TC), triglycerides (TG), and hemoglobin A1c (HbA1c) were measured. Residual
      stenosis was compared between the low Lp(a) group (< 30 mg/dL) and the high Lp(a)
      group (> or = 30 mg/dL). It was severe in the high Lp(a) group (85.0 +/- 24.9% vs
      94.5 +/- 15.5%, P = 0.0044). We also compared residual stenosis and TIMI
      classification between younger and older, non-DM and DM, non-HT and HT, low-TC (<
      220 mg/dL) and high-TC (> or = 220 mg/dL), low-TG (< 150 mg/dL) and high-TG (> or
      = 150 mg/dL), and low-Lp (a) and high-Lp (a) patients. Only the serum Lp (a)
      level affected the residual stenosis and TIMI classification (P < 0.05).
      CONCLUSION: These findings suggest that elevated Lp (a) levels inhibit
      fibrinolysis.

PMID- 15240961
TI  - Hemostatic and fibrinolytic activation is less following cutting balloon
      angioplasty of the coronary arteries.
AB  - Recent studies have shown that percutaneous coronary intervention (PCI) activates
      systemic hemostatic activity, reflecting platelet activation and thrombin
      formation in the coronary arteries. The present study compared systemic levels of
      hemostatic markers induced by plain old balloon angioplasty (POBA), coronary
      stenting (STENT), and cutting balloon (CB) angioplasty. Sixty-one patients with
      stable angina pectoris, who underwent elective PCI or diagnostic coronary
      angiography (CAG) alone, were investigated. Patients who underwent PCI were
      divided into the POBA group (n = 11), the STENT group (n = 27), and the CB group
      (n = 11). Patients who underwent CAG alone were assigned to the CAG group (n =
      12). Blood samples were collected before, 24 hours after, and 3 days after PCI or
      CAG. Plasma concentrations of prothrombin fragment 1+2 (F1+2), fibrinopeptide A
      (FPA), thrombin-antithrombin III complex (TAT), and plasminogen activator
      inhibitor-1 (PAI-1) were measured. In the CB group, the F1+2 (1.23 +/- 0.4
      nmol/L) level 3 days after PCI was significantly smaller than that of the POBA
      group (2.37 +/- 0.5 nmol/L) (P < 0.05). The FPA (1.81 +/- 0.9 ng/mL), TAT (3.36
      +/- 1.2 ng/mL) and PAI-1 (23.0 +/- 4.1 ng/mL) levels in the CB group 3 days after
      PCI were significantly smaller than those of the POBA group (P < 0.05,
      respectively) and STENT group (P < 0.05, respectively), but similar to the CAG
      group. Systemic hemostasis is activated to a greater extent after POBA and
      stenting than it is after CB angioplasty of the coronary arteries. This may
      contribute to the favorable long-term outcome of CB angioplasty.

PMID- 15240962
TI  - Comparison of exercise QRS amplitude changes in patients with slow coronary flow
      versus significant coronary stenosis.
AB  - Exercise Q, R, and S wave amplitude changes, called the QRS score, have been
      reported to be a marker of exercise-induced myocardial ischemia. Therefore, in
      this study, using the exercise QRS score, we sought to determine if slow coronary
      flow (SCF) phenomenon is associated with the exercise-induced myocardial
      ischemia. This retrospective study included 23 patients evaluated for suspected
      coronary artery disease and found to have SCF (group I) and 19 subjects with
      angiographically-defined significant coronary artery stenosis (group II). All
      study subjects underwent treadmill exercise testing using the modified Bruce
      protocol. For each subject the amplitude of the Q, R, and S waves in leads aVF
      and V5 was measured manually using calipers before and immediately after
      exercise. The QRS score was calculated by subtracting the Q, R, and S wave
      differences in leads aVF and V5. There was no difference between the two groups
      with respect to demographic properties. The peak heart rate achieved, baseline
      and peak systolic-diastolic blood pressure, exercise duration, and the metabolic
      equivalent values were similar in both groups. The maximum ST-segment depression
      ratio was significantly lower in patients with SCF than those of significant
      coronary stenosis (0.8 +/- 0.4 vs 1.3 +/- 0.5 P = 0.001, respectively). However,
      the exercise QRS score was found to be similar in both groups (3.3 +/- 2.3 vs 2.1
      +/- 3.0 P = 0.2, respectively). The data suggest that SCF phenomenon may alone
      lead to myocardial ischemia even in the absence of obstructed major epicardial
      coronary arteries as detected by similar exercise QRS scores to those of
      significant coronary artery stenosis.

PMID- 15240963
TI  - Sequential evaluation of left ventricular systolic and diastolic function after
      radiofrequency catheter ablation.
AB  - Radiofrequency (RF) catheter ablation has become standard therapy for many types
      of arrhythmias. RF energy may cause deterioration in left ventricular function by
      damaging the myocardium. The aim of the present study was to assess the changes
      in left ventricular function after catheter ablation using various
      echocardiographic parameters. Forty patients (22 women), aged 37 +/- 14 years
      (range, 15-76 years), underwent catheter ablation for various tachycardias.
      Routine echocardiogaphic examination was done in all patients. Left ventricular
      systolic function was evaluated by the modified Simpson method and tissue
      Doppler. With regard to left ventricular diastolic function parameters, diastolic
      early (E) and late (A) transmitral filling velocities, deceleration time (DT),
      isovolumetric relaxation time (IVRT), and tissue Doppler parameters were
      assessed. All ventricular function parameters were assessed before, and 1 hour, 1
      day, and 1 month after the catheter ablation procedure. To avoid any influence of
      heart rate on diastolic function parameters, the E/A ratio, DT, and IVRT were
      adjusted to heart rate (cE/A, cDT, cIVRT). No changes in left ventricular
      systolic function after the ablation were observed. After the ablation procedure
      (1 hour, 1 day, and 1 month) the cE/A ratio decreased from 1.42 +/- 0.43 to 1.19
      +/- 0.40, 1.18 +/- 0.40, and 1.30 +/- 0.33 (P = 0.009), respectively. cDT
      increased from 210 +/- 54 to 272 +/- 64, 255 +/- 60, 240 +/- 64 (P = 0.001),
      respectively. Likewise cIVRT increased from 113 +/- 22 to 133 +/- 54, 123 +/- 27,
      117 +/- 19 (P = 0.007), respectively. Significant changes were also observed
      concerning tissue Doppler parameters in assessing diastolic function. Although no
      significant changes were observed in systolic function after RF ablation, this
      procedure may have some detrimental effects on ventricular diastolic function
      para-meters.

PMID- 15240964
TI  - C-reactive protein and atrial fibrillation. Is inflammation a consequence or a
      cause of atrial fibrillation?
AB  - To clarify whether inflammation is a cause or consequence of atrial fibrillation
      (AF), we measured high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL
      6), and tumor necrosis factor alpha (TNF-alpha) before and after pharmacological
      cardioversion in 15 patients with paroxysmal AF. Levels of hs-CRP, IL-6, and TNF
      alpha after cardioversion were significantly higher than those in controls (P <
      0.05). Furthermore, the levels of these indices did not differ significantly even
      at 24 hours and 2 weeks after cardioversion. These results suggest that
      inflammation is a causative agent of paroxymal AF.

PMID- 15240965
TI  - The relationship between echocardiographic features of mitral valve and elastic
      properties of aortic wall and Beighton hypermobility score in patients with
      mitral valve prolapse.
AB  - The present study was designed to investigate the incidence of benign joint
      hypermobility syndrome (BJHMS) in mitral valve prolapse (MVP) and the correlation
      between the echocardiographic features of the mitral valve and elastic properties
      of the aortic wall and Beighton hypermobility score (BHS) in patients with MVP
      and BJHMS. Fourty-six patients with nonrheumatic, uncomplicated, and isolated
      mitral anterior leaflet prolapse (7 men and 39 women, mean age; 26.1 +/- 5.9) and
      25 healthy subjects (3 men and 22 women, mean age, 25.4 +/- 4.3) were studied.
      Patients were divided into two groups according to their BHS (group I, MVP+BJHMS;
      group II, MVP-BJHMS). Individuals with accompanying cardiac or systemic disease
      were excluded. Echocardiographic examination was performed in all subjects. The
      presence of BJHMS was evaluated according to Beighton's criteria. The incidence
      of BJHMS in patients with MVP was found to be significantly higher than that of
      controls (45.6%, (21/46) vs 12% (3/25), P < 0.0001). Group I (MVP + BJHMS) had
      significantly increased anterior mitral leaflet thickness (AMLT, 3.4 +/- 0.4 vs
      3.1 +/- 0.3; P < 0.005), maximal leaflet displacement (MLD, 2.4 +/- 0.4 vs 1.7 +/
      0.4; P < 0.005), and degree of mitral regurgitation (DMR, 17.1 +/- 7.2 vs 11.2
      +/- 4.4; P < 0.01) compared to group II. However, the index of aortic stiffness
      (IAOS) was found to be lower (17.6 +/- 6.9 vs 23.9 +/- 7.6; P < 0.005) and aortic
      distensibility (AOD) to be higher (0.0035 +/- 0.007 vs 0.0024 +/- 0.005; P <
      0.005) in group I. There was a significant correlation between AMLT, MLD and DMR,
      and BHS (r = 0.57/P = 0.007, r = 0.55/P < 0.009, r = 0.51/P < 0.01,
      respectively). In addition, AOD correlated positively with BHS (r = 0.53/P <
      0.005), but the index of aortic stiffness correlated inversely with BHS (r = 
      0.49/P < 0.007). The incidence of BJHMS in patients with MVP was more frequent
      than the normal population and there was a significant correlation between the
      severity of BJHMS (according to BHS) and echocardiographic features of the mitral
      leaflets and elastic properties of the aortic wall.

PMID- 15240966
TI  - Reproducibility of intravenous intermittent triggered myocardial contrast
      echocardiography in healthy subjects.
AB  - Few data have been published on the reproducibility of baseline subtracted peak
      intensity obtained from intravenous intermittent triggered myocardial contrast
      echocardiography. We investigated the reproducibility of the peak intensity
      measured from intravenous intermittent triggered myocardial contrast
      echocardiography in 10 young healthy males. The contrast echocardiography was
      obtained using the second harmonic mode with an intravenous bolus injection of
      Levovist (first study). The same myocardial contrast echocardiography was
      repeated after the first study (second study). The myocardial opacification and
      peak intensity in the 12 segments of the apical 4 and 2 chamber views were
      assessed visually and quantitatively. The differences in the peak intensity
      between the initial and repeated measurements in the first study (intraobserver
      reproducibility) and between the initial measurements in the first and second
      studies (interinjection reproducibility) were assessed using the Bland and Altman
      method. The degree of opacification was good or intermediate in 207/228 (91%) of
      the segments. The agreement of myocardial opacification between the first and
      second studies was 87/114 (76%). However, significantly higher peak intensity was
      obtained in apical septal (8200 +/- 6300 au2) and mid septal (8500 +/- 6000 au2)
      segments in the 4 chamber view and in the mid inferior (12400 +/- 9300 au2) and
      apical inferior (10700 +/- 6300 au2) segments in the 2 chamber view compared with
      other segments. The mean differences of the peak intensities according to the
      Bland and Altman analysis was -1600 +/- 5000 au2 in the intraobserver
      reproducibility study, and -1100 +/- 5300 au2 in the interinjection
      reproducibility study. Thus, the measurement error was determined to range from
      8400 au2 to 9500 au2 in both studies. We conclude that the peak intensity
      obtained from intravenous intermittent triggered myocardial contrast
      echocardiography using Levovist varies significantly among segments in the left
      ventricular myocardium. Large intraobserver and interinjection variability exists
      in the measurement of peak intensity, suggesting that the reproducibility of this
      technique is limited for quantitative assessment of myocardial perfusion.

PMID- 15240967
TI  - Whole-heart dipyridamole stress first-pass myocardial perfusion MRI for the
      detection of coronary artery disease.
AB  - A whole-heart coverage MRI sequence, which employes a hybrid of fast gradient
      echo and echo planar acquisition imaging (FastCard EchoTrain), has recently been
      developed. Using this sequence, a first-pass myocardial perfusion MRI was shown
      to be a good noninvasive modality for detecting coronary artery disease (CAD) in
      a clinical setting. In addition, the clinical usefulness of delayed enhanced MRI
      has recently been reported. The objectives of this study were (1) to investigate
      the accuracy of dipyridamole stress first-pass myocardial perfusion MRI for
      diagnosing CAD (> 50% stenosis) and (2) to clarify whether additional delayed
      enhancement MRI has any clinical significance. We performed first-pass myocardial
      perfusion MRI in 102 consecutive patients (66 +/- 9 years old) suspected to have
      CAD or new lesions in patients with well-documented prior myocardial infarction
      (MI). Using a 1.5 T cardiac MR imager (GE CV/i), eight short axis MR images of
      the left ventricle were acquired by injecting gadolinium (0.1 mmol/kg) under
      dipyridamole infusion stress (0.56 mg/kg). Fifteen minutes later, aminophylline
      (250 mg) was injected and first-pass perfusion MRI was repeated in the resting
      state in order to evaluate both the presence of perfusion defect and delayed
      enhancement. The presence of perfusion defect and delayed enhancement was
      determined based on a visual qualitative analysis by the agreement of two
      separate readers who were blinded to any clinical information. Based on the
      stress and rest findings, no defect, reversible defect, or fixed defect with or
      without delayed enhancement was recorded in any patient. The MR findings revealed
      76 CAD patients, including 24 MI patients with new lesions and 26 patients
      without CAD on coronary angiography. The presence of stress perfusion defect had
      a 93% sensitivity and an 85% specificity for diagnosing CAD. A fixed defect
      showed an 86% sensitivity and a 66% specificity for diagnosing a prior MI.
      Patients with a fixed defect with delayed enhancement had more significant
      stenosis in the infarct related artery than in those without any enhancement
      (11/26 vs 15/20, P < 0.05). Dipyridamole stress first-pass myocardial perfusion
      MRI using the FastCard EchoTrain was found to be a clinically useful and accurate
      modality for diagnosing CAD.

PMID- 15240968
TI  - Endothelin-1 and nitric oxide levels in patients with mitral annulus
      calcification.
AB  - Mitral annulus calcification (MAC) is a chronic degenerative noninflammatory
      process. The goal of this study was to determine endothelin-1 (ET-1) and nitric
      oxide (NOx) levels in patients with MAC and compare them with those in normal
      subjects. The study group included 39 patients [26 females (66%), age, 63 +/- 8
      years] with MAC and 20 [11 females (55%), age, 61 +/- 7 years] healthy subjects.
      The patients were divided into two subgroups, group A with severe MAC and group B
      with mild MAC, according to the severity of the MAC. Plasma ET-1 levels were
      higher and NOx levels were lower in patients than controls [(6.5 +/- 5.6 pg/mL vs
      3.7 +/- 2.9 pg/mL for ET-1 and 35.0 +/- 10.6 micromol/L vs 42.3 +/- 9.9
      micromol/L for NOx; P < 0.05 for both)]. In the subgroups, ET-1 levels were
      higher in group A than group B (8.65 +/- 6.84 pg/mL vs 4.74 +/- 3.45 pg/mL, P <
      0.05) and the control group (8.65 +/- 6.84 pg/mL vs 3.70 +/- 2.88 pg/mL, P <
      0.05). There was no difference between group B and the control group. Plasma NOx
      levels were significantly decreased in group A compared to controls (32.22 +/-
      11.88 micromol/L vs 42.25 +/- 9.99 micromol/L, P < 0.05). However, no significant
      difference was observed between group B (37.38 +/- 9.06 micromol/L) and the other
      groups. Diabetes mellitus, coronary artery disease, and dyslipidemia were
      significantly associated with ET-1 levels. However, this association was not
      observed for NOx. In conclusion, patients with MAC have increased ET-1 and
      decreased NOx levels. This seems to be more prominent in patients with severe
      MAC.

PMID- 15240969
TI  - Possible involvement of macrophage-colony stimulating factor in the pathogenesis
      of cardiac dysfunction in hemodialysis patients.
AB  - In patients with end stage renal disease on hemodialysis (HD), left ventricular
      (LV) function is frequently impaired. However, the mechanism of the LV
      dysfunction is totally unknown. It has been suggested that overproduction of
      nitric oxide induced by inflammatory cytokines may contribute to the LV
      dysfunction in some diseased states. In this study, we examined whether
      inflammatory cytokines play a role in the altered LV function in HD patients. The
      plasma concentrations of 5 major inflammatory cytokines, including interleukin
      (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor-alpha, and macrophage-colony
      stimulating factor (M-CSF) were measured by enzyme immunoassay with horseradish
      peroxidase in 18 consecutive patients on HD and in 16 control subjects. Then, we
      examined the relationship between plasma concentrations of M-CSF and LV ejection
      fraction (EF) on echocardiography. Among the inflammatory cytokines examined,
      only the plasma concentrations of M-CSF were significantly elevated in patients
      on HD as compared to the control subjects. There was no significant change in the
      M-CSF concentrations before and after HD. Furthermore, there was a significant
      negative correlation between the plasma concentrations of M-CSF and LVEF. These
      results suggest that elevated levels of plasma M-CSF may exist prior to the
      development of LV dysfunction observed in HD patients.

PMID- 15240970
TI  - Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years
      old with myocardial infarction.
AB  - Several studies claim that prothrombin 20210GA and factor V Leiden mutations are
      related to arterial thrombosis. We investigated the frequencies of these
      mutations and their significance in the development of early atherosclerosis in
      acute myocardial infarction (AMI) patients younger than 55 years of age. We
      investigated 96 patients with AMI and 77 control subjects. The diagnosis of AMI
      was established by typical chest pain and ST elevations on the presentation
      electrocardiogram and characteristic cardiac enzyme elevations. None of the
      control subjects had evidence of cardiovascular disease. DNA samples were
      isolated from all subjects and prothrombin 20210GA and factor V Leiden mutations
      were determined by the RealTime PCR technique with the aid of a Light Cycler
      device. The prevalence of factor V Leiden mutation was 6.3% and 5.2% in the
      patient and control groups, respectively (OR 0.6 [95% CI 0.1- 3.9], P = 0.6),
      whereas the prevalence of prothrombin G20210A mutation was 4.2% and 2.6% in the
      patient and control groups, respectively (OR 2.8 [95% CI 0.2 - 32.2], P = 0.4).
      None of the patients had both mutations. Prothrombin 20210GA and factor V Leiden
      mutations are not significant risk factors for the development of myocardial
      infarction in patients less than 55 years old in Southern Turkey.

PMID- 15240971
TI  - Transvenous catheter cryoablation of the atrioventricular node and visual
      assessment of freezing of cardiac tissue using intracardiac echocardiography.
AB  - We investigated the use of a catheter-based cryoablation system on
      atrioventricular (AV) junction ablation in dogs. In five dogs, the cryoablation
      catheter was introduced to the AV junction area in order to create transient high
      degree or complete AV block. Cryo-freezing energy was applied by lowering the
      temperature to -75 degrees C for five minutes as a single cycle. This cycle was
      repeated until significant impairment of the AV conduction appeared. Transient
      high degree and complete AV block was obtained in all five dogs without any
      adverse effects. The iceball formation was identified by intracardiac
      echocardiography. Ablation of the AV junction is effective with several freeze
      thaw cycles using a transvenous catheter cryoablation system.

PMID- 15240972
TI  - Single coronary artery with anomalous origin of the right coronary artery from
      the left anterior descending artery with a unique proximal course.
AB  - A 62-year-old man with hypertension and hypercholesterolemia was referred to our
      unit for evaluation of chest pain. A very rare variant of single coronary artery,
      in which the anomalous right coronary artery originated as a separate branch from
      the left anterior descending artery, was incidentally found on his coronary
      angiography. The anomalous right coronary artery in our case appears to be unique
      in that it courses intraseptally rather than rightwards proximally and has
      obstructive atherosclerotic lesions resulting in inferior ischemia. Moreover, the
      acute angle made by the anomalous right coronary artery to turn toward the
      atrioventricular groove may have reduced the flow velocity and contributed to the
      development of inferior ischemia.

PMID- 15240974
TI  - Chylous ascites and pleural effusion secondary to constrictive pericarditis
      presenting with signs of lymphatic obstruction.
AB  - Chylous ascites is a clinical entity characterized by accumulation of milky fluid
      containing high amounts of triglycerides in the peritoneal cavity. The cause is
      usually lymphatic obstruction secondary to neoplastic processes. Constrictive
      pericarditis rarely causes cylous ascites through elevated venous pressure and
      lymphatic stasis. To the best of our knowledge, there is no report of
      constrictive pericarditis leading to chylous ascites in a patient presenting with
      objective lymphangiographic findings of lymphatic obstruction rather than stasis.
      We present a case of chylous ascites and pleural effusion secondary to
      constrictive pericarditis presenting with signs of lymphatic obstruction in
      lymphangio-graphy, in whom complete clinical and laboratory improvement was
      achieved after pericardiectomy.

PMID- 15240973
TI  - Pulmonary artery stenosis due to external compression by a calcified pericardial
      band.
AB  - A 60-year-old male with exertional dyspnea was referred to our hospital. Right
      pulmonary artery stenosis due to external compression by a calcified band was
      diagnosed by echocardiography, computed tomography, and magnetic resonance
      imaging. Percutaneous transluminal angioplasty was conducted in vain due to
      vascular recoil and failure of stent delivery. Pulmonary bypass grafting was
      performed successfully. The surgery indicated a probable etiology of chronic
      pericarditis. This is an extremely rare case of adult pulmonary artery stenosis
      without a known history of congenital disease, constrictive pericarditis,
      tuberculosis, or surgery.

PMID- 15240975
TI  - A case of asymptomatic cardiopericardial hydatid cyst.
AB  - Cases with cardiac hydatid cyst disease are uncommon, being approximately 0.2-2%
      of all cases. Most cardiac hydatid cysts are located in the interventricular
      septum or left ventricular wall. Pericardial location is very rare. We report a
      42-year old Turkish man with pericardial hydatid cyst disease who was otherwise
      asymptomatic, having no cardiac symptomatology. The most appropriate
      therapeutical option for a hydatid cyst is surgical removal of the cyst mass.
      However, our patient refused surgical treatment and thus medical treatment with
      albendazole was initiated. Following the first month of the drug therapy,
      pericardial effusion disappeared. The cystic nature of the mass disappeared and
      was solidified at the 6th month of treatment. The patient has been followed-up by
      us asymptomatically.

PMID- 15240976
TI  - Atherosclerosis and peripheral neurological problems.

PMID- 15240977
TI  - Sequences and timing of dental eruption in semi-free-ranging mandrills
      (Mandrillus sphinx).
AB  - The chronology of tooth emergence is often used to examine the growth and
      development of individuals and to compare life histories across species.
      Emergence patterns are also used to age animals and to infer life history
      influences for extinct species. However, comparative studies of primates are
      hindered by a lack of dental development data for many species. Here we describe
      the sequences and timing of tooth emergence for a large sample of semi-free
      ranging mandrills (Mandrillus sphinx) and compare this with other life history
      variables for this species. Deciduous dentition emerged in the sequence i1 i2 c
      p3 p4. The augmented sequence (including information about variability in
      emergence sequence) was i1 i2 [c p3] p4 for the female maxilla and the male
      mandible, and i1 i2 c p3 p4 for the female mandible and the male maxilla.
      Deciduous dentition was complete by 5.0 months in females and 6.4 months in
      males. The permanent dentition began to emerge at 26 months, and complete adult
      dentition had emerged by 68 months for males and 85 months for females. Sex
      differences occurred in the augmented eruption sequences: females M1 I1 I2 [M2 C]
      P3 P4 M3, males M1 I1 [I2 M2] [P4 = P3 = C] M3. The order of tooth eruption and
      the occurrence of sequence polymorphisms were very similar to those observed for
      baboons and macaques. Comparison with life history variables showed that
      mandrills have complete deciduous dentition at weaning, females possess both
      adult incisors and M1 when they first reproduce, but still have deciduous canines
      and premolars, and that both sexes have full adult dentition before they attain
      their full adult stature and mass.

PMID- 15240978
TI  - Footfall patterns, stride length and speed of vertical climbing in spider monkeys
      (Ateles fusciceps robustus) and woolly monkeys (Lagothrix lagotricha).
AB  - Vertical climbing is central to theories surrounding the locomotor
      specialisations of large primates. In this paper, we present spatiotemporal gait
      parameters obtained from video recordings of captive spider monkeys (Ateles
      fusciceps robustus) and woolly monkeys (Lagothrix lagotricha) in semi-natural
      enclosures, with the aim of discovering the influence of body weight and
      differences in general locomotor behaviour on vertical climbing kinematics on
      various substrates. Results show that there are only few differences between gait
      parameters of climbing on thin trees, vertical and oblique ropes, while climbing
      on large-diameter trees differs considerably, reflecting the higher costs of
      locomotion on the latter. At the same speed, Ateles takes longer strides and the
      support phase takes a smaller percentage of cycle duration than in Lagothrix.
      Footfall patterns are more diverse in Ateles and include a higher proportion of
      ipsilateral limb coupling. Compared to other primates, the gait characteristics
      of vertical climbing of atelines most closely resemble those of African apes.

PMID- 15240979
TI  - Does mom need more protein? Preliminary observations on differences in diet
      composition in a pair of red titi monkeys (Callicebus cupreus).

PMID- 15240980
TI  - Predation of crabs by tufted capuchins (Cebus apella) in Eastern Amazonia.

PMID- 15240981
TI  - A rare feeding observation on water lilies (Nymphaea alba) by the capped langur
      (Trachypithecus pileatus).

PMID- 15240982
TI  - On self-scratching in captive mandrills (Mandrillus sphinx).

PMID- 15240983
TI  - Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in
      treating associated migraine symptoms.
AB  - Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering
      capacity has been developed. In this double-blind, 3-arm, multicenter, parallel
      group study, 433 patients were treated either with 1,000 mg effervescent ASA or
      50 mg encapsulated sumatriptan or placebo. The primary endpoint was the
      percentage of patients with complete remission of the 3 accompanying symptoms
      nausea, photophobia and phonophobia within 2 h after intake of the study drug.
      43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan
      and 30.9% of patients treated with placebo showed complete remission of all 3
      accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active
      treatments were superior to placebo regarding the individual symptoms photophobia
      and phonophobia, but not for nausea. The percentage of patients with reduction in
      headache severity from moderate or severe to mild or no pain (secondary
      objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All
      active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of
      patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug
      related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated
      with placebo, ASA or sumatriptan. The study showed that administration of
      effervescent ASA leads to remission of the migraine symptoms nausea, photophobia
      and phonophobia, reduces migraine headache and is comparable to sumatriptan.

PMID- 15240984
TI  - Sensory neuropathy as revealing symptom of neurolymphomatosis: report of a case
      with a 15-year duration.

PMID- 15240985
TI  - New CACNA1A gene mutation in a case of familial hemiplegic migraine with status
      epilepticus.

PMID- 15240986
TI  - Treatment of dermatomyositis and polymyositis with anti-tumor necrosis factor
      alpha: long-term follow-up.

PMID- 15240987
TI  - Isolated posterior interosseous nerve palsy subsequent to Campylobacter jejuni
      enteritis.

PMID- 15240988
TI  - Reprocessed (high-flux) Polyflux dialyzers resist trans-membrane endotoxin
      passage and attenuate inflammatory markers.
AB  - BACKGROUND: Bacterial contamination of dialysis water can contribute to the
      chronic microinflammatory state observed in dialysis patients. This study
      characterized the selective permeability of new and peroxyacetic acid/acetic
      acid/hydrogen peroxide (Renalin) reprocessed high-flux, polyarylethersulfone
      polyvinylpyrrolidone (Polyflux-17R) dialyzers after exposure to endotoxin
      contaminated dialysate during in vitro dialysis. Clinical correlation with pre
      dialysis levels of systemic markers of inflammation, and clearance of middle
      molecules was also assessed in vivo. METHODS: Six hemodialysis (HD) patients were
      enrolled in the study. After reuses 0, 1, 5, 10, and 15, the dialyzers were
      reclaimed and submitted to an in vitro dialysis circuit using standard dialysate
      and blood from healthy volunteers. New and reprocessed dialyzers were
      sequentially exposed to escalating doses of Pseudomonas aeruginosa endotoxin in
      the dialysate compartment, and whole blood tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) production was used as an index of reverse
      passage of endotoxin. In vivo, IL-6, C-reactive protein (CRP) and serum amyloid A
      (SAA) levels were measured to assess the impact of reprocessing on the systemic
      inflammatory response. Finally, pre- and post-dialysis samples were collected to
      measure urea and beta(2)-microglobulin (beta(2)-M) clearances. RESULTS: During in
      vitro dialysis, blood-side endotoxin levels were undetectable following dialysate
      contamination. TNF-alpha production remained unchanged (p = NS), and IL-6
      production fell significantly on reuses 0, 1, 10, and 15 (p = 0.03) suggesting
      membrane adsorption, as a result of reuse-dependent surface binding. In vivo,
      whereas IL-6 and SAA levels did not significantly differ (p = 0.90 and 0.59,
      respectively), CRP levels fell near significantly, over the course of 15 reuses
      (p = 0.06). In vivo, beta(2)-M clearance was not affected by the reuse technique
      (p = 0.28). CONCLUSIONS: This study provides in vitro and in vivo evidence
      arguing that high-flux Polyflux dialyzers provide more than adequate dialysis,
      while preventing the in vitro back-diffusion of bacterial endotoxin despite 15
      reuses with Renalin. Clinically, this may translate into an attenuation of the
      microinflammatory milieu.

PMID- 15240989
TI  - Screening for retinopathy of prematurity: is it painful?
AB  - BACKGROUND: Screening programmes for retinopathy of prematurity have shown to
      reduce unfavourable visual outcome and to be cost-effective. Following present
      recommendations, almost 1% of all newborn babies should therefore be screened and
      undergo at least one ophthalmologic examination. This is a skilled procedure that
      requires drug instillation and manipulation of the ocular globe with scleral
      indentation. The objective of this study is to describe the side effects of this
      ophthalmic exam with special focus on the occurrence of pain. METHODS: This was
      an observational study with a before-after analysis where all neonates undergoing
      an ophthalmologic exam during a 4-month period in a third level hospital were
      included. CRIES pain score was determined before the exam, 5 min after and 24 h
      after the screening manoeuvre. Blood pressure and pulse rate were determined in
      addition to the mentioned measurements 30 min after the ophthalmologic
      examination. Minimum oxygen saturation, apnoeas, gastrointestinal side effects
      (like vomiting and gastric aspirates), the need for respiratory assistance or for
      intensive care unit admission were recorded within 24 h before and after the
      procedure. RESULTS: 27 preterm neonates underwent an ophthalmologic examination
      and were included in the study. CRIES pain score was significantly higher 5 min
      after and 24 h after the screening procedure than before. This difference was
      also observed after stratification for birth weight and gestational age. No other
      study variable modified this time effect. No significant changes in blood
      pressure and pulse rate were shown after the ophthalmic exam. Vomiting was
      present in 4% of the newborns, gastric aspirates in 22% and apnoeas in 41% after
      the examination. Ten percent of the explored preterm babies needed increased
      respiratory assistance and 4% had to be transferred from the intermediate care
      unit to the intensive care because of severe apnoeas. COMMENTS: An increase in
      pain score was shown after retinopathy of prematurity screening examination.
      Physiologic variable changes do not last long enough to evaluate the impact of
      certain procedures. Multivariate pain scores (like CRIES) should be used in
      everyday practice. It seems that the ophthalmologic examination in preterm babies
      might be painful and further studies should identify the best strategy to prevent
      pain during the retinopathy of prematurity screening manoeuvre.

PMID- 15240990
TI  - Symptom dimensions in obsessive-compulsive disorder: factor analysis on a
      clinician-rated scale and a self-report measure.
AB  - Although obsessive-compulsive disorder (OCD) is regarded as a unitary nosological
      entity, it encompasses a rich variety of heterogeneous mental and behavioural
      phenomena. The identification of clinical subtypes within this broad concept has
      been a focus of attention in recent years. In the present study, we administered
      a clinician-rated scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with
      the Y-BOCS Symptom Checklist (Y-BOCS CL), as well as a self-report questionnaire,
      the Padua Inventory revised (PI-R), to 150 outpatients with OCD. A principal
      component analysis on the Y-BOCS CL, along with the PI-R, identified 6 consistent
      symptom clusters: (1) contamination obsessions and cleaning compulsions, (2)
      sexual/religious/somatic obsessions and checking, (3) high risk assessment and
      checking, (4) impulses and fear of loss of control, (5) need for symmetry and
      exactness, and ordering and counting compulsions, and finally (6) rumination. The
      Y-BOCS CL and PI-R showed great overlap and consistency regarding content and
      severity of the OCD symptoms. On inspection of items with identical content, only
      half of the items showed significant agreement. Both inventories have unique
      factors: rumination is represented solely in the PI-R, somatic obsessions and
      checking solely in the Y-BOCS CL. This means that the use of both clinician
      administered and self-report measures is recommended, so that the entire spectrum
      of symptoms is represented.

PMID- 15240991
TI  - A case of Sotos syndrome (cerebral gigantism) and psychosis.
AB  - Sotos syndrome, or cerebral gigantism, is a syndrome of accelerated growth during
      early childhood, and a number of craniofacial and other physical abnormalities
      are commonly present. Behavioral and psychiatric manifestations of the disorder
      include attention deficits, aggressiveness, and social inhibition. The authors
      describe a case of psychosis that developed in a patient with Sotos syndrome.

PMID- 15240992
TI  - Nitric oxide agents and apomorphine-induced rat behaviors.
AB  - BACKGROUND: Nitric oxide (NO) may alter dopamine release in the brain. Activation
      of D2-dopamine receptors may suppress NO synthase, and inhibition of NO synthase
      prevents behaviors induced by psychostimulants. We have investigated the
      modulatory actions of the precursor of NO synthesis (L-arginine) and the broad
      spectrum NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on
      apomorphine-induced behaviors in the rat. METHODS: Apomorphine was injected
      subcutaneously, and behaviors induced by the drug were examined in the presence
      or absence of intracerebroventricular administration of L-arginine and L-NAME.
      RESULTS: Our data indicate that L-arginine or L-NAME treatment decreased licking
      and yawning, but not penile erection induced by apomorphine. CONCLUSION:
      Apomorphine-induced behaviors may be modulated by NO levels.

PMID- 15240993
TI  - Antiallergic activity of hesperidin is activated by intestinal microflora.
AB  - When hesperidin isolated from pericarpium of Citrus unshiu (family Rutaceae) was
      incubated with human intestinal microflora, its main metabolite was hesperetin,
      which was a main metabolite in urine of orally hesperidin-administered rats. The
      antiallergic activity of hesperidin and its metabolite hesperetin were
      investigated. Hesperidin did not inhibit the histamine release from RBL-2H3 cells
      induced by IgE. However, its metabolite hesperetin potently inhibited the
      histamine release from RBL-2H3 cells induced by IgE and the PCA reaction. The
      inhibitory activity of hesperetin was found to be comparable with azelastine, a
      commercially available antiallergic drug, and to potently inhibit prostaglandin
      E2 production in lipopolysaccharide-stimulated RAW 264.7 cells. Hesperetin weakly
      inhibits cyclooxygenase 2 enzyme activities. These results suggest that
      hesperidin may be a prodrug, which is metabolized to hesperetin by intestinal
      bacteria.

PMID- 15240994
TI  - Induction of proliferation by 15-deoxy-delta12,14-prostaglandin J2 and the
      precursors in monocytic leukemia U937.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in
      several human tumors including gastric, lung, colon, prostate and breast.
      However, the role of PPARgamma signals in leukemia is still unclear. The aim of
      this study is to evaluate the ability of 15-deoxy-Delta12,14-prostaglandin J2
      (15dPGJ2), that is a ligand for PPARgamma, on proliferation of human leukemia
      cell line U937. 15dPGJ2 at 5 micromol/l stimulated the proliferation. In
      contrast, 15dPGJ2 at concentrations of >10 micromol/l inhibited the proliferation
      through the induction of apoptosis. PGD2, PGJ2 and Delta12-PGJ2 (DeltaPGJ2),
      those are precursors of 15dPGJ2, had similarly proliferative effects, whereas
      they showed antiproliferative effects at high concentrations. FACScan analysis
      revealed that PGD2 at 5 micromol/l, PGJ2 at 1 micromol/l, DeltaPGJ2 at 1
      micromol/l and 15dPGJ2 at 5 micromol/l, all accelerated cell cycle progression.
      Immunoblotting analysis revealed that PGD2 at 5 micromol/l and 15dPGJ2 at 5
      micromol/l inhibited the expression of phospho-p38, phospho-MKK3/MKK6 and phospho
      ATF-2, and the expression of Cdk inhibitors including p18, p27. In contrast, PGJ2
      at 1 micromol/l and DeltaPGJ2 at 1 micromol/l did not affect the expression of
      them. These results suggest that 15dPGJ2 and PGD2 may, through inactivation of
      the p38 MAPK pathway, inhibit the expression of Cdk inhibitors, leading to
      acceleration of proliferation.

PMID- 15240995
TI  - Presynaptic excitability as a potential target for the treatment of the traumatic
      cerebellum.
AB  - Using an extracellular recording method, we have previously shown a
      hyperexcitability of the presynaptic response in fluid percussion injury (FPI) in
      rats. In this study, we demonstrated that treatment with cis-ACBD, a glutamate
      reuptake inhibitor, depressed the presynaptic potential (PSP) in naive/sham
      controls, while it potentiated the PSP in FPI rats. On the contrary, (RS)-APICA,
      a selective group II metabotropic glutamate receptor antagonist, potentiated PSP
      in controls, but depressed PSP in FPI rats. These results indicate that an
      alteration of the normal function of metabotropic glutamate receptors and
      glutamate reuptake system or an altered reactivity of presynaptic fibers was
      induced by FPI. This alteration may contribute to the reported loss of Purkinje
      cells after FPI. PSP may be used as a potential tool for evaluating treatments of
      FPI or as a potential target for the prevention of Purkinje cell death.

PMID- 15240996
TI  - S-Adenosylmethionine protects against acetaminophen-induced hepatotoxicity in
      mice.
AB  - An overdose of acetaminophen (APAP) is the most frequent cause of fulminant liver
      failure in the United States. Increasing evidence demonstrates that oxidative
      stress plays an important etiologic role in APAP-induced liver injury. S
      Adenosylmethionine (SAMe) is a key intermediate in the hepatic trans-sulfuration
      pathway and serves as a precursor for glutathione (GSH) as well as the methyl
      donor in most transmethylation reactions. In the present study, we investigated
      effects of SAMe on liver injury induced by APAP administration in male C57BL/6
      mice. Two related studies were performed. In the first experiment, SAMe (1g/kg
      BW) was injected intraperitoneally 4 h before APAP (600 mg/kg BW) administration.
      In the second experiment, SAMe was injected intraperitoneally 1 h after APAP
      administration. Our results showed that APAP administration induced changes
      typical of confluent centrilobular necrosis by histological examination and a
      marked elevation in serum alanine aminotransferase (ALT) activity. APAP
      administration induced significant decreases in both hepatic and blood SAMe
      concentrations. In addition, APAP decreased intracellular (both cytosolic and
      mitochondrial) GSH concentrations along with increased lipid peroxidation in
      conjunction with mitochondrial dysfunction as documented by Ca2+-induced
      mitochondrial permeability transition. SAMe treatment (both before and after
      APAP) significantly attenuated the liver injury. Exogenous SAMe prevented the
      decrease in liver and blood SAMe concentrations. Moreover, SAMe treatment
      attenuated both cytosolic and mitochondrial GSH depletion as well as
      mitochondrial dysfunction. We conclude that SAMe at least in part protects the
      liver from APAP-induced injury by preventing intracellular GSH depletion and
      mitochondrial dysfunction.

PMID- 15240997
TI  - Mechanism of CGRP-induced vasodilation in the rat isolated perfused kidney.
AB  - We investigated the intracellular mechanisms involved in calcitonin gene-related
      peptide (CGRP)-induced vasodilation in rat isolated perfused kidney. CGRP-1
      receptor antagonist, CGRP-8-37, abolished the responses. Endothelial denudation
      by Triton X-100 or nitric oxide (NO) synthase inhibition by NG-nitro-L-arginine
      attenuated the maximum dilation by about 63 and 55%, respectively. Protein kinase
      A inhibitor, KT-5720, caused an about 72% inhibition in CGRP-induced maximum
      dilation. Soluble guanylate cyclase inhibitor, ODQ, and ATP-sensitive potassium
      channel blocker, glibenclamide, inhibited the CGRP-induced maximum responses by
      75 and 55%, respectively. Cyclooxygenase inhibitor, indomethacin, had no effect.
      Our data suggest that CGRP-1 receptors, endothelium, NO synthase, protein kinase
      A, soluble guanylate cyclase, and ATP-sensitive potassium channels, but not the
      cyclooxygenase pathway, may play a role in CGRP-induced vasodilation in rat
      isolated perfused kidney.

PMID- 15240998
TI  - Effects of hormones targeting nuclear receptors on transcriptional regulation of
      the growth hormone gene in the MtT/S rat somatotrope cell line.
AB  - We have examined the effects of nuclear receptor hormones such as glucocorticoid,
      gonadal steroid hormones, thyroid hormone and retinoids on the transcriptional
      regulation of the 5'-promoter activity of growth hormone (GH) gene using the
      MtT/S rat pure somatotrope cell line or MtT/SGL, a subclone of MtT/S in which the
      rat GH gene 5'-promoter (1.7 Kb)-luciferase fusion gene was stably incorporated.
      RT-PCR analyses revealed that receptors for all the hormones except androgen
      receptor were expressed in the cell line. Triiodothyronine (T(3), 10 nM)
      transiently but significantly stimulated the promoter activity of GH gene,
      whereas retinoic acids (9-cis and all-trans, both 1 microM) showed sustained
      stimulation. There were no additive effects among the T(3), all-trans, and9-cis
      retinoic acids. Synthetic glucocorticoid hormone dexamethasone (100 nM) showed an
      inhibitory effect but, interestingly, significantly enhanced T(3)-stimulated GH
      promoter activity during long-term incubation. Among the gonadal steroid hormones
      tested, estradiol and estriol had significant stimulatory effects, and deletion
      analysis showed that the estrogen effect was maintained with the shortest
      construct examined (-150 to +6, +1 denotes the transcription start site). These
      results suggest that thyroid hormone and retinoids stimulate the transcription of
      GH gene, probably through a common response element, whereas glucocorticoid has
      both negative and positive effects on GH expression, depending on the combination
      with other hormones and the time of exposure. Estrogens also have direct
      stimulatory effects through the proximal promoter region of GH gene.

PMID- 15240999
TI  - Vaccine engineering improved by hybrid technology.
AB  - The term 'vaccination' describes the induction of protective immune responses
      against infectious diseases, but is also used to define antigen-specific forms of
      immunotherapy for allergy, cancer and autoimmunity. Successful vaccination
      requires either immune modulation or the induction of robust specific immunity to
      several disease-causing antigens. However, natural antigen sources may contain
      greatly varying amounts of these antigens and some of them may exhibit low
      immunogenicity. An approach for overcoming the latter problems has been developed
      for allergy vaccines recently. This approach is based on the genetic engineering
      of hybrid molecules, consisting of several major disease-eliciting
      antigens/epitopes. Such hybrid molecules can be built to include the most
      relevant epitopes of complex antigen sources. Moreover, fusion of different
      antigens in the form of hybrid molecules strongly increases their immunogenicity.
      The hybrid approach can also be used for the generation of mosaic antigens with
      altered immunological properties, which consist of re-shuffled antigen pieces. We
      exemplify the use of hybrid technology for the generation of new allergy vaccines
      and discuss its potential applicability for the development of vaccines for
      infectious diseases, cancer and autoimmunity.

PMID- 15241000
TI  - Images iin Allergy and Immunology. Mouse spleen basophils.

PMID- 15241001
TI  - The latex allergen hev B 5 is an antigen with repetitive murine B-cell epitopes.
AB  - BACKGROUND: Hev b 5 is a potent latex allergen. In this study, we characterize
      the linear B-cell epitopes for three monoclonal antibodies (mAbs) to Hev b 5.
      METHODS: The mAbs included 2 IgG1 (6A10, 3G3) and 1 IgG2b (6F6) isotypes. We used
      SPOTscan analysis with overlapping octapeptides to identify the binding regions
      for the antibodies and then methionine substitution analysis to further define
      the critical amino acids (aa) in each epitope. Site-directed mutagenesis was used
      to selectively eliminate the IgG binding for each epitope and single and multiple
      mutations were expressed as recombinant GST fusion proteins. Antibody recognition
      of the mutant proteins was determined by inhibition ELISA. RESULTS: All three
      mAbs recognized the same aa sequence by SPOTs analysis with slight variations,
      and this epitope was repeated 3 times in the Hev b 5 sequence; APETEK (63-68),
      PAEGEK (120-125), and PAEEEK (126-131). Sequential methionine substitution by
      SPOTsalogue identified K68, E122, and K131 as critical aa in each epitope to
      change by site-directed mutagenesis. Inhibition ELISA with the mutant proteins
      indicated that epitope 126-131 was the dominant epitope, but mutation of epitope
      120-125 was also required to eliminate mAb reactivity to Hev b 5. The antibodies
      did not appear to recognize the epitope 63-68 in the recombinant fusion protein.
      CONCLUSIONS: We identified an immunodominant B-cell epitope in Hev b 5 that is
      repeated 3 times within the sequence, making Hev b 5 multivalent. Well
      characterized monoclonals recognizing repeated epitopes would be a good choice
      for immunodetection of Hev b 5 in glove extracts where individual epitopes could
      get altered by the manufacturing process.

PMID- 15241002
TI  - Evaluation of lyophilised, gamma-irradiated amnion as a biological dressing.
AB  - Burns, non-healing wounds and pressure sores cause extensive damage to the skin
      leading to infection and loss of precious body fluids. Despite advances in burn
      management the mortality rate continues to be high and the search for an
      economical and easily available dressing to control burn wound infection
      continues. Autologous skin has limited availability and is associated with
      additional scarring. Conventional dressings require frequent changes which can be
      painful and may even require anaesthesia. Amnion is an excellent biological
      dressing and its use in the treatment of burns has special appeal in India as
      there are religious barriers to the acceptance of bovine and porcine
      skin.Lyophilised, irradiated amnion provided for the first time in the country by
      the Tata Memorial Hospital Tissue Bank was evaluated as a temporary biological
      dressing. It was used to treat 35 patients with burns, 21 patients with bedsores
      and non-healing ulcers and the skin graft donor sites of 11 patients. The amnion
      was easy to handle and stuck well to the raw wound bed. An open dressing was used
      in most of the second degree burns which healed with hyperemia and early
      pigmentation. In patients with third degree burns, ulcers or skin graft donor
      sites, closed dressings were used. The exudate and induration were reduced and
      patients were more comfortable and experienced less pain. There was healthy
      granulation with good re-epithelialisation. Amnion was not used in patients with
      infected third degree burns.

PMID- 15241003
TI  - Effect of patient, operative and isolation factors on subsequent yield and
      viability of human hepatocytes for research use.
AB  - It is widely accepted that the model of choice for pharmacotoxicological studies
      are human hepatocytes. There is therefore a demand for these cells, but quality
      must be maintained for their widespread use. We present a retrospective review of
      the isolation of hepatocytes from both surgically resected tissue and livers
      rejected for transplantation, and evaluated patient, operative and isolation
      variables to ascertain which may affect the viability and yield of cells. Seven
      clinically rejected whole livers and 60 surgically resected specimens (from two
      distinct operating centres) were isolated. For surgically resected tissue we
      found that decreasing age, securing the perfusing cannulae with suture rather
      than reforming Glissons capsule with glue and steatotic livers improved
      viability. No significant correlation could be found with pre-operative blood
      results, disease, type of operation, presence or absence of Pringle manoeuvre,
      weight of tissue isolated, time of digestion with collagenase and cold ischaemic
      time. There was a reduction in mean yield and viability when hepatocyte
      isolations were performed in livers rejected for transplant, compared to
      surgically resected tissue although this did not reach significance. Human
      hepatocytes can be successfully and consistently isolated from surgically
      resected tissue and appear to be superior to those isolated from rejected for
      transplant livers. From our study, there are few parameters that significantly
      affect the quality of isolated hepatocytes, which increases the possible pool of
      tissue that hepatocytes can be isolated from.

PMID- 15241004
TI  - Applied tissue engineering in the closure of severe burns and chronic wounds
      using cultured human autologous keratinocytes in a natural fibrin matrix.
AB  - Whereas in severe burns cultured human epithelial cells may well serve as a life
      saving method, the true value of tissue-engineered skin products in chronic wound
      care has yet to be clearly defined. Among other well-known clinical problems, the
      engraftment rate of commercially available multilayered "sheet grafts" has been
      shown to vary extremely. Adherence of transplanted cells to the wound bed-
      especially in the presence of potential wound contamination-- is one of the
      crucial aspects of this technique. Keratinocyte suspensions in a natural fibrin
      sealant matrix can potentially treat a variety of skin defects. In acute burn
      wounds, as well as in chronic wounds the clinical application of this type of
      tissue-engineered skin substitute demonstrates the capacity of cultured human
      autologous keratinocytes in a fibrin sealant matrix to adhere to wound beds,
      attach and spread over the wound resulting in reepithelialization of both acute
      and chronic wounds. In full thickness burns the combination of this new tool with
      allogenic dermis is a promising option to achieve complete dermal-epidermal
      reconstitution by means of tissue engineering and guided tissue repair. When
      transferring this technique into the treatment of chronic wounds we found an
      optimal preparation of such recipient wound beds to be crucial to the success.
      The additional application of continuous negative pressure (vacuum therapy) and
      preliminary chip skin grafting to optimally prepare the recipient site may be
      helpful tools to achieve such well-prepared and graftable surfaces. Prospective
      controlled comparative studies should be designed to further assess the clinical
      efficacy of this technique.

PMID- 15241005
TI  - Very long-term radiographic and bone scan results of frozen autograft and
      allograft bone grafting in 17 patients (20 grafts) a 30- to 35-year follow-up.
AB  - In the early 1950s, 48 patients received bone implants from a bone bank in Tel
      Hashomer Hospital that stored frozen autograft and allograft bones at
      temperatures less than -17 degrees C. Seventeen (35%) of these patients (20
      implants), 10 men and 7 women, with a mean age of 52.4 (34-69) years were
      available for follow-up after a mean period of 32.5 (30-35) years. They underwent
      clinical examination, radiographs and bone scans to evaluate their surgical
      results. Fracture healing, non-union, graft resorption, osteoporosis and bone
      sclerosis were used as radiographic criteria for bone incorporation, and normal,
      increased and decreased uptake served to assess the bone scan. Based on the above
      criteria, the results were satisfactory in 17 (85%) and poor in 3 (15%). The
      three failures were after shelf operation for hip dysplasia that used two
      allografts and one autograft. Allogenous or a combination of allogenous with
      autogenous frozen bone grafts proved to be a satisfactory and durable method for
      filling bone defects.

PMID- 15241006
TI  - Functional assessment of cryopreserved human femoral arteries for pharmaceutical
      research.
AB  - An established method for cryopreservation that might preserve the vascular and
      endothelial responses of human femoral arteries (HFAs) to be transplanted as
      allografts was studied. HFAs were harvested from multiorgan donors and stored at
      4 degrees C in saline solution before cryostorage. Thirty HFA rings were isolated
      and randomly assigned to one control group of unfrozen HFAs (eight rings) and one
      group of cryopreserved HFAs (22 rings). Cryopreservation was performed in RPMI
      solution containing dimethylsulfoxide (DMSO) and the rate of cooling was -1
      degrees C/min until -40 degrees C and faster rates until -150 degrees C was
      reached. The contractile and relaxant responses of unfrozen and frozen/thawed
      arteries were assessed in organ bath by measurement of isometric force generated
      by the HFAs. After thawing, the maximal contractile responses to the contracting
      agonist tested (noradrenaline) were in the range of 43% of the responses in
      unfrozen HFAs. The endothelium-independent responses to sodium nitroprusside were
      not altered whereas the endothelium-dependent relaxant responses to acetylcholine
      were weakly altered. The cryopreservation method used provided a limited
      preservation of contractility of HFAs, a good preservation of the endothelium
      independent relaxant responses, and a good preservation of endothelium-dependent
      relaxation. It is possible that further refinements of the cryopreservation
      protocol, such as a slower rate of cooling and a more controlled stepwise
      addition of DMSO, might allow better post-thaw functional recovery.

PMID- 15241007
TI  - Functional assessment of cryopreserved pig aortas for pharmaceutical research.
AB  - Several in vitro studies have demonstrated diminished post-thaw functional
      activity. Therefore, the aim of this study was to investigate the consequences of
      thawing and storage method used on the post-thaw functional activity of
      cryopreserved pig aortas with the aim of adjusting the freezing and thawing
      protocol so that the vascular segments are preserved in the best possible state,
      maintaining structure and functionality so that they can later be transplanted
      with success. In vitro responses of frozen, thawed pig aortas were used to
      investigate the functional activity after thawing at 15 degrees C and 100 degrees
      C/min and after storage in gas or liquid phase of liquid nitrogen.
      Cryopreservation was performed in RPMI 1640 medium + 10% dimethylsulfoxide and
      the rate of cooling was -1 degrees C/min, until -150 degrees C was reached. After
      thawing the maximal contractile responses to all the contracting agonists tested
      (KCl, noradrenaline) were in the ranges of 13-27% compared with the responses in
      unfrozen pig aortas. Contractile responses were slightly better when thawing was
      performed at 15 degrees C/min compared with 100 degrees C/min. The endothelium
      independent relaxant responses to sodium nitroprusside were reduced ( P < 0.05).
      Cryostorage of pig arteries also resulted in a loss of the endothelium-dependent
      relaxant response to acetylcholine. The cryopreservation method used provided a
      limited preservation of pig aorta contractibility, a reduction of the endothelium
      independent relaxant responses, and no apparent preservation of the endothelium
      dependent relaxation. It is possible that further refinements of the
      cryopreservation protocol might allow better post-thaw functional recovery of pig
      aortas.

PMID- 15241009
TI  - Influence of osteoprotegerin (OPG) on resorption of heterotopically induced
      ossicle.
AB  - In this paper, the effect of osteoprotegerin (OPG) on slowing down the resorption
      process of heterotopically induced bone tissue is described. The induced ossicle
      is resorbed ex inactivitate. This system mimics osteoporosis in immobilised
      skeletal bones. Bone induction was achieved in BALB/c mice after the injection of
      the suspension of 3 x 10(6) HeLa cells into thigh muscle of animals immuno
      suppressed by a single dose of hydrocortisone. To slow down the process of
      resorption we applied OPG and measured quantitatively the effect by weighing the
      mass of mineral deposited in the induced ossicle after hydrolysis of soft tissues
      surrounding the induced ossicles. As the effect of application of OPG more than
      340-540% of bone mineral is found in the induced ossicles following nine
      applications of 0.05 mg OPG per mouse, every second day--in comparison to the
      control animals.

PMID- 15241008
TI  - Functional assessment of cryopreserved human aortas for pharmaceutical research.
AB  - We evaluated the impact of standard cryopreservation on functional properties of
      human aortic homografts. From seven human donors, the thoracic descending aorta
      was obtained. Effects of cryopreservation on contractibility and endothelium
      function were tested. After cryopreservation no endothelium-dependent or
      endothelium-independent relaxation was found and the contractibility was strongly
      affected. Arteries showed no function and loss of endothelial integrity after
      cryopreservation and thawing.

PMID- 15241010
TI  - Radiation processed amniotic membranes in the treatment of non-healing ulcers of
      different etiologies.
AB  - The amniotic membranes were collected from the placentae of selected and screened
      donors. Processing was done by washing the fresh amniotic membrane successively
      in sterile saline, 0.05% sodium hypochlorite solution and sterile distilled water
      until it was completely cleared of blood particles. The membranes were sterilized
      by gamma irradiation at 25 kGy. The processed amniotic membranes were applied to
      50 open wounds comprising of 42 full thickness defects and eight partial
      thickness defects. These included leprotic, diabetic, traumatic, gravitational
      ulcers and superficial burn in the form of scald and corrosive burn. The
      radiation processed amniotic membranes favoured healing of unresponsive and non
      healing ulcers of different etiologies. Ulcers with duration of minimum 3 weeks
      to maximum 12 months were found to heal in 2-6 weeks by the application of
      amniotic membranes.

PMID- 15241011
TI  - Targeted generation of 16 sequence-tagged sites for bovine chromosome region 5q21
      q25 by microdissection.
AB  - The cattle chromosome region BTA5q21-q25 is associated with immune defense and is
      linked with several economically important traits for growth, ovulation, twinning
      and milk yield. Chromosome microdissection of the region was performed to
      generate fragment-specific DNA libraries and to provide new bovine-specific DNA
      sequences as starting material for physical fine-mapping approaches or linkage
      studies. A first library screening resulted in the identification of 16 region
      specific sequence-tagged sites (STS). Fifteen STS represent new unique cattle DNA
      sequences, of which one identifies a new microsatellite. Homology with the gene
      CDK2 was found for the remaining STS.

PMID- 15241012
TI  - Evolution of genome organizations of squirrels (Sciuridae) revealed by cross
      species chromosome painting.
AB  - With complete sets of chromosome-specific painting probes derived from flow
      sorted chromosomes of human and grey squirrel (Sciurus carolinensis), the whole
      genome homologies between human and representatives of tree squirrels (Sciurus
      carolinensis, Callosciurus erythraeus), flying squirrels (Petaurista albiventer)
      and chipmunks (Tamias sibiricus) have been defined by cross-species chromosome
      painting. The results show that, unlike the highly rearranged karyotypes of mouse
      and rat, the karyotypes of squirrels are highly conserved. Two methods have been
      used to reconstruct the genome phylogeny of squirrels with the laboratory rabbit
      (Oryctolagus cuniculus) as the out-group: (1) phylogenetic analysis by parsimony
      using chromosomal characters identified by comparative cytogenetic approaches;
      (2) mapping the genome rearrangements onto recently published sequence-based
      molecular trees. Our chromosome painting results, in combination with molecular
      data, show that flying squirrels are phylogenetically close to New World tree
      squirrels. Chromosome painting and G-banding comparisons place chipmunks (Tamias
      sibiricus ), with a derived karyotype, outside the clade comprising tree and
      flying squirrels. The superorder Glires (orde Rodentia + order Lagomorpha) is
      firmly supported by two conserved syntenic associations between human chromosomes
      1 and 10p homologues, and between 9 and 11 homologues.

PMID- 15241013
TI  - Generation of chromosome painting probes from single chromosomes by laser
      microdissection and linker-adaptor PCR.
AB  - Fluorescence in situ hybridization (FISH) plays an essential role in research and
      clinical diagnostics. The versatility and resolution of FISH depends critically
      on the probe set used. Here, we describe an improved approach for the generation
      of specific DNA probes from single copies of chromosomes. Single chromosomes or
      single chromosomal regions were microdissected by laser pressure catapulting and
      amplified using linker-adaptor PCR. The probes were labeled and tested in various
      scenarios including multicolor-FISH experiments employing up to seven different
      fluorochromes. FISH confirmed the specific and even staining of the respective
      chromosomal regions. Furthermore, the capability of these probes to detect even
      small translocations (<3 Mb) suggests that the dissected regions are completely
      represented in the generated painting probes.

PMID- 15241014
TI  - TSPY, the candidate gonadoblastoma gene on the human Y chromosome, has a widely
      expressed homologue on the X - implications for Y chromosome evolution.
AB  - TSPY, a candidate gene for a factor that promotes gonadoblastoma formation (GBY),
      is a testis-specific multicopy gene family in the male-specific region of the
      human Y (MSY) chromosome. Although it was originally proposed that male-specific
      genes on the Y originated from a transposed copy of an autosomal gene (Lahn &
      Page 1999b), at least two male-specific genes (RBMY and SRY) descended from a
      formerly recombining X-Y identical gene pair. Here we show that a TSPY homologue
      with similar gene structure lies in conserved positions, close to SMCX, on the X
      chromosome in human (TSPX ) and mouse (Tspx). TSPX is widely expressed and
      subject to X inactivation. TSPX and TSPY therefore evolved from an identical gene
      pair on the original mammalian sex chromosomes. This supports the hypothesis that
      even male-specific genes on the Y chromosome may have their origin in
      ubiquitously expressed genes on the X. It also strengthens the case for TSPY as a
      candidate for GBY, since independent functional studies link TSPX to cell cycle
      regulation.

PMID- 15241015
TI  - A lineage-specific centromeric satellite sequence in the genus Trifolium.
AB  - We report the molecular structure, genomic organization, chromosomal distribution
      and evolutionary dynamics of TrR350, a satellite DNA isolated from the forage
      legume white clover (Trifolium repens L.; 2n = 4 x = 32). The basic repeating
      unit is an A+T rich 350 bp Hin dIII fragment with a complex dimeric structure
      consisting of an internal direct repeat of 156 bp packed between unrelated
      flanking sequences. Each 156 bp repeat has a conserved 24 bp motif repeating at
      two places. Most of the 24 bp short repeating units enclose a pentanucleotide
      CAAAA motif, presumed to be involved in breakage-reunion mechanism of tandemly
      repeating arrays. The dimers share high sequence homology among themselves while
      monomers within dimers show significant sequence divergence. Genomic Southern
      hybridization and/or fluorescence in situ hybridization (FISH) on 17 Trifolium
      species/subspecies revealed that it is a lineage-specific repeat confined to
      several species within the section Lotoidea originating in the Mediterranean
      region. The uniform length of the basic repeating unit and the centromeric
      localization in most of the species harbouring it reflects its extensive
      conservation in the lineage. However, the Hin dIII restriction profile in seven
      species also indicated independent evolution of this repeat.

PMID- 15241016
TI  - Autosome and sex chromosome diversity among the African pygmy mice, subgenus
      Nannomys (Murinae; Mus).
AB  - The African pygmy mice, subgenus Nannomys, constitute the most speciose lineage
      of the genus Mus with 19 recognized species. Although morphologically very
      similar, they exhibit considerable chromosomal diversity which is here confirmed
      and extended by the G-banding analysis of 65 mice from West and South Africa. On
      the basis of their karyotype and distribution area, the specimens were assigned
      to at least five species. Extensive differentiation both within and between
      species was observed that involved almost exclusively Robertsonian
      translocations, 23 of which are newly described. Two of the rearrangements were
      sex chromosome-autosome translocations, associated in some cases with partial
      deletions of the X or Y chromosomes. Several authors have predicted that the
      highly deleterious effect of this rearrangement would be reduced if the sex and
      autosomal segments were insulated by a block of centromeric heterochromatin. The
      C-banding analyses performed showed that among the species carrying X-autosome
      translocations, one followed the expected pattern, while the other did not. In
      this case, functional isolation of the sex and autosome compartments must involve
      other repetitive sequences or genomic traits that require further molecular
      characterization. Such studies will provide insight into the causes and
      consequences of the high diversity of sex chromosome rearrangements in this
      subgenus.

PMID- 15241017
TI  - Karyotypic evolution of Apodemus (Muridae, Rodentia) inferred from comparative
      FISH analyses.
AB  - We conducted comparative FISH analyses to investigate the chromosomal
      rearrangements that have occurred during the evolution of the rodent genus
      Apodemus, which inhabits broadleaf forests in the temperate zone of the
      Palaearctic region. Chromosome-specific painting probes of the laboratory mouse
      were hybridized to chromosomes of seven Apodemus species, A. agrarius, A.
      argenteus, A. gurkha, A. peninsulae, A. semotus, A. speciosus and A. sylvaticus,
      and homologous chromosomal regions were determined in the species for the study
      of karyotypic evolution. Differences in the hybridization patterns were found in
      nine pairs of autosomes among the seven species. The chromosomal location of the
      5S rRNA genes on the telomeric region of chromosome 20 was highly conserved in
      all the species. In contrast, there was much wider variation in the location of
      the 18S-28S rRNA genes, although they were predominantly located on chromosomes
      7, 8 and 12. Phylogenetic relationships of the seven Apodemus species were
      inferred from the chromosome rearrangements and the chromosomal distribution
      patterns of the 18S-28S rRNA genes. The karyotypic relationships correlated well
      with the molecular phylogeny, and A. semotus had the most highly conserved
      karyotype among the seven species.

PMID- 15241018
TI  - Laying the cytotaxonomic foundations of a new model grass, Brachypodium
      distachyon (L.) Beauv.
AB  - Brachypodium distachyon is a ubiquitous, temperate grass species which is being
      developed and exploited as an alternative model to rice, in order to gain access
      to important syntenic regions of the genomes of less tractable relatives such as
      wheat. As part of this initiative, this paper describes for the first time the
      cytotaxonomy of members of the polyploid series of this species, and challenges
      the assumption that the series evolved simply by chromosome doubling. In situ
      hybridization using genomic DNA probes and rDNA markers uncovers a hybrid origin
      of several of the polyploid ecotypes, and sheds light upon the complex evolution
      of this species and its close relatives.

PMID- 15241019
TI  - Mapping the distribution of the telomeric sequence (T2AG3)n in the 2n = 14
      ancestral marsupial complement and in the macropodines (Marsupialia:
      Macropodidae) by fluorescence in situ hybridization.
AB  - In this study we test the theory that the presence of the conserved vertebrate
      telomeric sequence (T(2)AG(3))(n) at the centromeres of Australian marsupial 2n =
      14 complements is evidence that these karyotypes are recently derived, which is
      contrary to the generally held view that the 2n = 14 karyotype is ancestral for
      Australasian and American marsupials. Here we compare the distribution of the
      (T(2)AG(3))( n ) sequence and constitutive heterochromatin in the presumed
      ancestral 2n = 14 complement and in complements with known rearrangements. We
      found that where there were moderate to large amounts of constitutive
      heterochromatin, the distribution of the (T(2)AG(3))(n) sequence reflected its
      presence as a native component of satellite DNA rather than its involvement in
      past rearrangements. The presence of centromeric heterochromatin in all
      Australian 2n = 14 complements therefore suggests that centromeric sites of the
      (T(2)AG(3))(n) sequence do not represent evidence for recent rearrangements.

PMID- 15241070
TI  - Professional organization of healthcare-associated infection control: time for
      action across the patient care system.

PMID- 15241071
TI  - Severe acute respiratory syndrome: an update.
AB  - PURPOSE OF REVIEW: An international outbreak of severe acute respiratory
      syndrome, a recently recognized syndrome caused by the newly identified severe
      acute respiratory syndrome-associated coronavirus, began in November 2002 and
      ended in July 2003. Since then, a large body of research on the syndrome has been
      published; the most updated developments are summarized here. RECENT FINDINGS:
      Recent findings suggest that animal severe acute respiratory syndrome-like
      coronaviruses may have been transmitted to humans without detection for years
      before the recent outbreak, and that such transmission may be continuing today.
      The 2002-2003 outbreak probably originated from similar animal-to-human
      transmission, but selection and purification of the animal severe acute
      respiratory syndrome-like virus appears to have occurred, creating the more
      virulent severe acute respiratory syndrome-associated coronavirus. Recent studies
      have documented that severe acute respiratory syndrome-associated coronavirus is
      primarily transmitted via contact and/or respiratory droplets and that the
      combination of standard, contact, and droplet precautions is generally effective
      for its control. It has been shown that severe acute respiratory syndrome
      associated coronavirus is typically relatively inefficiently transmitted, with
      the notable exception of transmission during superspreading events. Insights into
      the pathogenesis of severe acute respiratory syndrome have been made: one study
      suggests that human leukocyte antigen HLA-B*4601 is a possible risk factor for
      more severe disease, while another identifies angiotensin-converting enzyme 2 as
      a cellular receptor for severe acute respiratory syndrome-associated coronavirus.
      Promising treatments have been identified, including interferons, an anti-spike
      monoclonal antibody, and fusion inhibitors. In addition, many promising vaccines
      are currently in development. SUMMARY: New findings regarding severe acute
      respiratory syndrome are continuing to be discovered at an unprecedented pace,
      permitting a better understanding of the disease and enabling better preparation
      for its possible return.

PMID- 15241072
TI  - Nosocomial infection surveillance and control policies.
AB  - PURPOSE OF REVIEW: In the majority of countries costs for health care are
      increasing and strategies to reduce adverse events in medical treatment have an
      increasing importance. Nosocomial infection remains the most common type of
      complication affecting hospitalized patients. As preventive strategies have
      indeed become more important they now have to show not only that they are
      effective in reducing nosocomial infections but also that they are cost
      effective. This paper investigates the contribution made by articles published in
      the last year to the development of nosocomial-infection surveillance and control
      policies. RECENT FINDINGS: At least 15 randomized controlled studies and six meta
      analyses investigating various infection-control policies were published last
      year. They did not lead to any changes in present guidelines, but rather endorsed
      existing recommendations. At least nine studies were found reporting a
      substantial reduction in nosocomial infections by the introduction of quality
      management principles under routine working conditions. Furthermore there were a
      lot of studies published which focused on optimizing surveillance measures and
      investigating the use of reference data for reducing infection rates. Only seven
      studies estimating the burden of disease were found in the literature of the past
      year. SUMMARY: The predominant opinion voiced in the studies was that in many
      medical institutions some 30% or more of nosocomial infections could be
      prevented.

PMID- 15241073
TI  - Update on vascular catheter infections.
AB  - PURPOSE OF REVIEW: Extensive reviews of our current understanding of vascular
      catheter infections have recently been published. This update highlights 22
      primary research articles selected from 415 randomized clinical trials and over
      2500 other articles on vascular catheter infections published between January
      2002 and March 2004. RECENT FINDINGS: Full sterile barriers are not necessary for
      the insertion of arterial catheters. Subcutaneous tunnels may decrease the risk
      of femoral catheter infection. The minocycline-rifampin catheter coating still
      appears to be the most efficacious. Further studies demonstrating that education
      of MD/RN personnel reduces the risk of catheter infection now exist. A number of
      studies show that the method of attaching IV tubing to catheters and certain
      catheter flush solutions can reduce the risk of infection. Differential time to
      positivity looks increasingly promising as a practical method for diagnosing
      catheter infection. All catheters suspected of infection do not need to be
      removed. The management of vascular catheter infections can be improved by a
      simple e-mail mechanism. SUMMARY: Abundant evidence now exists that there are
      many interventions that can reduce the risk of vascular catheter infections. The
      next phase of our understanding should include determining how many of these many
      interventions are necessary and under what circumstances.

PMID- 15241074
TI  - Epidemiology and control of antibiotic resistance in the intensive care unit.
AB  - PURPOSE OF REVIEW: Resistance to antibiotics is very high in the intensive care
      units of many countries, although there are several exceptions. Some infections
      are becoming extremely difficult to treat. The risk of cross-transmission of
      those strains is very high. This review focuses on recent data (2003 to the
      present) that may help understanding and dealing with this serious public health
      problem. RECENT FINDINGS: Intensive care units can be considered as 'factories'
      for creating, disseminating and amplifying resistance to antibiotics, for many
      reasons: importation of resistant microorganisms at admission, selection of
      resistant strains with an extensive use of broad-spectrum antibiotics, cross
      transmission of resistant strains via the hands or the environment. Some national
      programs can be considered as failures, as in the UK and the USA. Other countries
      have been able to maintain a low level of resistance (Scandinavian countries,
      Netherlands, Switzerland, Germany, Canada). There is clearly an 'inoculum effect'
      above which preventive measures become poorly efficient. Several preventive
      measures have been proposed including preventive isolation, systematic screening
      at admission, local, national or international antibiotic guidelines, antibiotic
      prescriptions advice by infectious-disease teams, antibiotic prevention with
      selective digestive decontamination, antibiotic strategies such as 'cycling', or
      rather, for some authors, the use of an 'a la carte' antibiotic strategy which
      could be considered as a 'patient-to-patient antibiotic rotation'. SUMMARY: There
      is obviously an international concern regarding the level of resistance to
      antibiotics in the intensive-care-unit setting. A strong program including
      prevention of cross-transmission and better usage of antibiotics seems to be
      needed in order to be successful. We do not know if this kind of program will
      enable countries with a very high endemic level of resistance to decrease the
      level in future years.

PMID- 15241075
TI  - Prevention and control of methicillin-resistant Staphylococcus aureus infections.
AB  - PURPOSE OF REVIEW: This article reviews many recent publications relevant to the
      prevention and control of nosocomial methicillin-resistant Staphylococcus aureus
      (MRSA) infection. RECENT FINDINGS: Higher risk-adjusted costs and mortality have
      been found for MRSA infections than for methicillin-susceptible S. aureus
      infections confirming their epidemiologic importance. Staphylococcal cassette
      chromosome mec, the genetic basis for MRSA, does not develop in methicillin
      susceptible S. aureus exposed to antimicrobials. Instead virtually all patients
      acquire MRSA via spread. Nevertheless, antibiotic therapy provides a selective
      advantage for such spread, especially within healthcare settings where
      antimicrobial therapy is most frequent. Several studies have suggested better
      control of MRSA through antibiotic control, but far more studies have reported
      control using surveillance cultures and contact precautions for preventing spread
      (rather than just using standard precautions). More rapid detection of MRSA
      (within 6 h) has been reported using polymerase chain reaction, but studies using
      this method to reduce spread have not yet been published. A structured survey of
      research methods used regarding MRSA control noted that many studies had
      methodologic shortcomings (for example, none was a randomized trial), but
      nevertheless concluded that active detection and isolation work should be used. A
      Society for Healthcare Epidemiology of America guideline emphasized the same
      approach noting that scores of studies on multiple continents had reported
      success with this approach, with best results in several northern-European
      countries where all facilities used it routinely. SUMMARY: Improved MRSA control
      is possible by detecting and isolating colonized patients.

PMID- 15241076
TI  - Nosocomial diarrhoea due to Clostridium difficile.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent developments
      in the diagnosis, epidemiology, treatment and prevention of nosocomial diarrhoea
      due to Clostridium difficile. RECENT FINDINGS: Twenty-five years after its
      discovery, the diagnosis of C. difficile-associated diarrhoea is still
      problematic with laboratories trying to reconcile the time and expense of the
      diagnostic process. Newer molecular techniques may offer hope. With the
      introduction of new antibiotics into clinical practice, confusion has arisen
      about the risk they pose for C. difficile-associated diarrhoea. Strains of C.
      difficile that fail to produce an active toxin A are an emerging problem and good
      molecular epidemiology is required to determine whether highly infectious clones
      exist. Little progress has been made in the treatment of recurrent C. difficile
      associated diarrhoea; however, the development of a vaccine is imminent. More
      effort is being made to rid the hospital environment of C. difficile through
      infection-control procedures or changes in antibiotic-prescribing policies.
      SUMMARY: C. difficile continues to be a major nosocomial infection in many health
      care institutions throughout the world. Strategies that reduce exposure to the
      organism or to antibiotics will have an impact on rates of C. difficile
      associated diarrhoea.

PMID- 15241077
TI  - Nursing resources: a major determinant of nosocomial infection?
AB  - PURPOSE OF REVIEW: There is growing concern that changes in nurse workforce and
      hospital-restructuring interventions negatively impact on patient outcomes. This
      review focuses on the association between understaffing and health-care
      associated infections. RECENT FINDINGS: There is a large number of studies
      showing that overcrowding, understaffing or a misbalance between workload and
      resources are important determinants of nosocomial infections and cross
      transmission of microorganisms. Importantly, not only the number of staff but
      also the level of their training affects outcomes. The nurse workforce is ageing,
      mainly due to fewer individuals' engaging in a nursing career. This phenomenon,
      combined with cost-driven downsizing, contributes to a nursing shortage, and this
      tendency is not expected to revert unless important system changes are
      implemented. The causal pathway between understaffing and infection is complex,
      and factors might include lack of time to comply with infection control
      recommendations, job dissatisfaction, job-related burnout, absenteeism and a high
      staff turnover. SUMMARY: The evidence that cost-driven downsizing and changes in
      staffing patterns causes harm to patients cannot be ignored, and should not be
      considered as an inevitable outcome. More research is needed to better define the
      optimal patient-to-nurse ratio in various hospital settings and to estimate the
      economical impact of the nursing shortage. All quality-improvement interventions
      should carefully take into account systems and processes to be successful, as the
      issue of staffing is essentially a structural problem.

PMID- 15241078
TI  - Immunization for hospital staff.
AB  - PURPOSE OF REVIEW: In this review the recent literature on the topic of
      immunization of healthcare workers is assessed. The emphasis lies on
      immunizations that are directly related to the risks of healthcare workers in the
      workplace. RECENT FINDINGS: Acceptance of influenza immunization by healthcare
      workers remains too low, whereas other preventive measures such as hepatitis B
      vaccination are usually not disputed. Efforts to improve the knowledge of
      healthcare workers about influenza, its epidemic potential and clinical
      consequences have contributed to higher immunization rates in some hospitals.
      Immunization against varicella zoster virus does not result in immunity in all
      vaccinated persons. This lack of complete protection has infection-control
      implications, namely the recommendation to wear a mask when caring for clinical
      cases, regardless of the immunization status. The topic of immunization of
      healthcare workers has recently been dominated by the discussion of smallpox
      vaccination, which was promoted by the American public-health authorities for
      some groups of healthcare workers. SUMMARY: Immunization is a preventive measure
      that is highly cost-effective. Healthcare workers are responsible for the safety
      and well-being of their patients and should do their utmost to prevent the
      transmission of infectious pathogens to them. Another positive result of the
      adherence of healthcare workers to the recommended immunization schedule is the
      improved self-protection at the workplace. Immunization against some highly
      contagious infectious agents has been recommended for many years. The list is now
      being expanded again by the recommendation of smallpox vaccination. Regarding
      this indication, several questions and safety issues must be resolved in order to
      positively influence the currently rather sceptical attitude of healthcare
      workers towards this vaccine.

PMID- 15241079
TI  - Successes and limitations of antimicrobial interventions in the setting of organ
      transplantation.

PMID- 15241080
TI  - Fungal infections in bone marrow transplant patients.
AB  - PURPOSE OF REVIEW: Invasive fungal infections have become the leading infectious
      cause of death in recipients of hematopoietic cell transplantation. Several
      factors have led to a renaissance in the study of invasive fungal infections. The
      growing incidence of both commonly encountered as well as emerging pathogens and
      the lethality of these infections coupled with the unprecedented number of
      available broad-spectrum antifungal drugs has lent a renewed vigor and enthusiasm
      to attempts to understand the pathogenesis of these diseases and, by doing so,
      improve prevention, diagnosis, and treatment. The following is a review of the
      primary research published from 2003 to the present that is pertinent to invasive
      fungal infection in the setting of hematopoietic cell transplantation. RECENT
      FINDINGS: The main themes of published primary research during 2003 to the
      present include the efficacy and tolerability of antifungal prophylaxis,
      epidemiologic analyses of risk factors following nonmyeloablative preparative
      regimens, and more-detailed analyses of nonmyeloid immune responses. SUMMARY:
      Although few definitive recommendations emerged from the studies during the
      review period, these investigations do contribute to a greater understanding of
      the immunobiology of invasive fungal infection and of the utility and limitations
      of newer antifungal agents in the prophylaxis or treatment of invasive fungal
      infection.

PMID- 15241081
TI  - Prophylactic strategies before solid-organ transplantation.
AB  - PURPOSE OF REVIEW: Prophylactic measures prior to organ transplantation are
      evolving based on recent reports of emerging infectious diseases, as well as an
      expanded understanding of the epidemiology of familiar infections. This review
      will highlight developments with potential impact on donor and recipient
      screening and pretransplant management. RECENT FINDINGS: Key findings regarding
      bacterial infections include the lack of utility of mupirocin intranasal
      decolonization for prevention of Staphylococcus aureus infections after liver
      transplantation, and the description of transmission of Pseudomonas infection to
      multiple recipients via an innominate artery graft. The implications of donor
      bacterial colonization in lung transplantation are further explored. The
      emergence of non-Candida albicans yeast and non-Aspergillus mold infections may
      lead to changes in prophylactic strategies. The majority of cystic fibrosis
      patients have had Aspergillus colonization at some time before transplant; one
      quarter of these develop tracheobronchial aspergillosis and anastomotic
      complications. There are several key developments regarding viral infections.
      Donor-derived human herpesvirus-8-infected neoplastic cells have been identified
      in recipients with Kaposi sarcoma. The transmission of human T-cell lymphotropic
      virus -1 (HTLV-1) to multiple recipients who developed myelopathy underscores the
      continuing need for donor screening. The striking event of West Nile virus
      transmission to multiple recipients from a single donor also has raised questions
      regarding donor screening for this virus. New information on the use of hepatitis
      B core antibody-positive donor livers, as well as the emergence of hepatitis B
      virus escape mutants, is discussed. Finally, information on successful
      retransplantation after BK polyomavirus (BKV) allograft nephropathy is beginning
      to appear. SUMMARY: The pretransplant phase continues to be an important time
      period for screening and intervention in order to reduce the risk of
      posttransplant infections. Recent findings add to our current understanding of
      epidemiology and risk stratification; however, more randomized trials are needed.

PMID- 15241082
TI  - Prevention and treatment of cytomegalovirus infection in solid organ transplant
      recipients.
AB  - PURPOSE OF REVIEW: Cytomegalovirus remains the single most important pathogen
      affecting solid organ transplant recipients. Its importance lies both in its
      effects and as a model for deciphering the clinical impact and management of
      other agents such as hepatitis C virus and other herpes viruses such as human
      herpes virus-6 and 7. The effects of cytomegalovirus infection in these patients
      can be divided into two categories: the direct causation of a wide variety of
      infectious disease syndromes; and the indirect effects, which include
      contributing to the net state of immunosuppression, allograft injury, and
      potentiating posttransplant lymphoproliferative disease. RECENT FINDINGS: The
      advent of valganciclovir, with its excellent oral bioavailability, combined with
      intravenous ganciclovir have provided powerful tools for controlling the direct
      effects of cytomegalovirus, particularly with the recognition that the intensity
      of the antiviral therapy has to be linked to the intensity of the
      immunosuppression required.Unfortunately, far less is known about the efficacy of
      antiviral therapy in managing the indirect effects of cytomegalovirus.
      Preliminary data suggest antiviral prophylaxis protects against acute allograft
      injury, as well as decreasing the incidence of some opportunistic infection.
      SUMMARY: A great deal of progress has been made in the prevention and treatment
      of the infectious disease syndromes caused by cytomegalovirus, with the
      development of the concept of the therapeutic prescription. This has two
      components: an immunosuppressive component to prevent and treat rejection and an
      antimicrobial component to make it safe. Much more information, however, is
      required.

PMID- 15241083
TI  - Natural history of hepatitis C following liver transplantation.
AB  - PURPOSE OF REVIEW: Currently, chronic hepatitis C virus-infection-related
      cirrhosis is the most common indication for liver transplantation in the USA and
      most parts of the world. While the incidence of new hepatitis C virus cases has
      decreased, the prevalence of infection will not peak until the year 2040. In
      addition, as the duration of infection increases, the proportion of new patients
      with cirrhosis will double by 2020 in an untreated patient population. If this
      model is correct, the projected increase in the need for liver transplantation
      secondary to chronic hepatitis C virus infection will place an impossible burden
      on an already limited supply of organs. In this article we present a
      comprehensive review of post-transplant hepatitis C virus infection and address
      the major challenges that face the transplant community. RECENT FINDINGS:
      Hepatitis C virus infection recurs virtually in every post-transplant patient.
      Typically, serum levels of hepatitis C virus RNA increase rapidly from week 2
      post-liver transplant, achieving 1-year post-liver transplant levels that are 10
      20-fold greater than the mean pre-liver transplant levels. Progression of chronic
      hepatitis C virus is more aggressive after liver transplantation with a
      cumulative probability of developing graft cirrhosis estimated to reach 30% at 5
      years. Approximately 10% of the patients with recurrent disease will die or
      require re-transplantation within 5 years post-transplantation. Interventions to
      prevent, improve, or halt the recurrence of hepatitis C virus infection have been
      evaluated by multiple small studies worldwide with similar overall rates of
      virological clearance of approximately 9-30%. Current consensus recommends
      combination therapy with pegylated interferon and ribavirin for those patients
      with histological recurrence of hepatitis C virus infection and fibrosis of >/=
      2/4. Therapy is adjusted to tolerance and rescued with granulocyte colony
      stimulating factor and erythropoietin for bone marrow suppression. SUMMARY: The
      major challenges that face the transplant community in the coming years include
      new strategies to meet the growing demand for limited organ donor supplies and
      improvement of treatment for those patients in whom recurrence of viral disease
      has occurred. Only with improved antiviral treatments and strategies will we make
      a significant impact on this problem.

PMID- 15241084
TI  - Bibliography. Current world literature. Nososcomial and hospital-related
      infections.

PMID- 15241088
TI  - Ethyl pyruvate ameliorates distant organ injury in a murine model of acute
      necrotizing pancreatitis.
AB  - OBJECTIVE: Ethyl pyruvate has been shown to be an effective anti-inflammatory
      agent in a variety of in vitro and in vivo model systems. Herein, we used a
      murine model of acute pancreatitis to compare the effects of treatment with
      either Ringer's lactate solution or ethyl pyruvate solution on several
      physiologic and biochemical variables related to disease severity. DESIGN:
      Experimental animal study. SETTING: University laboratory. SUBJECTS: C57Bl/6
      mice. INTERVENTIONS: Pancreatitis was induced by feeding the animals a choline
      deficient diet supplemented with 0.5% ethionine for 24 hrs and then challenging
      the animals with seven hourly 50 microg/kg intraperitoneal injections of cerulein
      and a single intraperitoneal injection of Escherichia coli lipopolysaccharide (4
      mg/kg). MEASUREMENTS AND MAIN RESULTS: When mice were treated with ethyl pyruvate
      (40 mg/kg intraperitoneally every 6 hrs for 48 hrs) instead of Ringer's lactate
      solution starting 2 hrs after the injection of lipopolysaccharide, long-term
      survival was improved from one of ten to six of ten (p =.057). When mice were
      treated with a 40 mg/kg dose of ethyl pyruvate just before the first dose of
      cerulein and then injected with a second 40 mg/kg dose 6 hrs later, serum
      concentrations of alanine aminotransferase measured 10 hrs after the first
      cerulein dose were significantly lower than in mice with pancreatitis treated
      with Ringer's lactate solution. In this model of acute pancreatitis, the same
      dosing regimen for ethyl pyruvate also ameliorated bacterial translocation to
      mesenteric lymph nodes and leakage of fluorescein isothiocyanate-labeled albumin
      from blood into bronchoalveolar lavage fluid. Treatment with ethyl pyruvate
      decreased pancreatic expression of tumor necrosis factor and interleukin-6
      messenger RNA and nuclear factor-kappaB DNA binding in nuclear extracts prepared
      from pancreatic tissue. CONCLUSION: Treatment with ethyl pyruvate ameliorated the
      local inflammatory response and decreased local and distant organ injury in a
      murine model of necrotizing pancreatitis.

PMID- 15241089
TI  - Delayed neutrophil apoptosis in sepsis is associated with maintenance of
      mitochondrial transmembrane potential and reduced caspase-9 activity.
AB  - OBJECTIVE: The resolution of neutrophil (PMN)-mediated inflammation occurs
      through the apoptosis, or programmed cell death, of the neutrophil. PMN apoptosis
      is inhibited by a variety of inflammatory stimuli; moreover, PMN from critically
      ill septic patients show profoundly delayed rates of apoptosis in vitro. Since
      apoptosis is effected through the activity of intracellular cysteine proteases
      (caspases), we evaluated caspase expression and activity in neutrophils from
      septic patients and compared them with caspase expression and activity of resting
      or lipopolysaccharide-activated neutrophils from healthy volunteers. DESIGN:
      Prospective observational cohort study. SETTING: Tertiary level intensive care
      unit and associated research laboratory. SUBJECTS: Thirty-six intensive care unit
      patients with sepsis; ten healthy laboratory controls. INTERVENTIONS: Collection
      of up to 10 mL of whole blood for in vitro study of rates of apoptosis,
      expression and activity of caspases-1, -3, and -9, activation of nuclear factor
      kappaB, and change in mitochondrial transmembrane potential. MEASUREMENTS AND
      MAIN RESULTS: Following 24 hrs of in vitro culture, 52 +/- 7.8% of control
      neutrophils, but only 29 +/- 5.4% of lipopolysaccharide-stimulated (1 microg/mL)
      PMN, showed nuclear changes of apoptosis. Only 6.2 +/- 1.1% of neutrophils from
      septic patients were apoptotic after 24 hrs. Significant nuclear translocation of
      nuclear factor-kappaB was evident in septic PMN, and inhibition of apoptosis was
      partially abrogated by prevention of nuclear factor-kappaB dissociation with
      pyrrolidine dithiocarbamate. Caspase-3 transcription and catalytic activity were
      significantly reduced in both patients' and lipopolysaccharide-treated PMN;
      caspase-1 transcription and activity were increased by lipopolysaccharide but
      reduced in septic patients. In contrast, caspase-9 transcription and activity
      were reduced in septic patients but not in lipopolysaccharide-treated PMN.
      Decreased caspase-9 activity was associated with sustained maintenance of
      mitochondrial transmembrane potential and reduced translocation of cytochrome c
      from the mitochondria to the cytosol. CONCLUSIONS: Apoptosis of circulating
      neutrophils from patients with clinical sepsis is profoundly suppressed, through
      a mechanism that involves activation of nuclear factor-kappaB that is associated
      with reduced activity of caspases-9 and -3 and maintenance of mitochondrial
      transmembrane potential and that differs in important respects from the
      inhibitory effects seen following the exposure of healthy neutrophils to
      inflammatory stimuli.

PMID- 15241090
TI  - Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal
      cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease
      pulmonary edema in experimental acid-induced lung injury.
AB  - OBJECTIVE: To determine whether clinically relevant airspace concentrations of
      beta2-adrenergic agonists stimulated maximal alveolar fluid clearance rates and
      to determine whether beta2 agonist therapy decreased pulmonary edema in
      experimental acute lung injury. DESIGN: Prospective randomized laboratory
      investigation. SETTING: University-affiliated laboratory. SUBJECTS: Sprague
      Dawley rats. INTERVENTIONS: Dibutyryl cyclic adenosine monophosphate (cAMP),
      salmeterol, albuterol, and isoproterenol in normal rat lung. Salmeterol in a rat
      model of acid-induced lung injury. MEASUREMENTS AND MAIN RESULTS: Basal alveolar
      fluid clearance was 7.6 +/- 2.2 %/hr. Maximal cAMP-dependent alveolar fluid
      clearance rate was 32.9 +/- 10.9 %/hr (p <.05). Racemic albuterol 10(-5) M,
      salmeterol 10(-6) M, and isoproterenol 10(-6) M each stimulated alveolar fluid
      clearance to a level comparable to maximal cAMP-dependent alveolar fluid
      clearance. Compared with basal rates, alveolar fluid clearance was increased by
      both racemic albuterol 10(-6) M (14.5 +/- 3.0%, p <.05) and R-enantiomer 10(-6) M
      (15.0 +/- 4.6%, p <.05), but there was no difference between the two groups.
      Intra-alveolar salmeterol 10 (-6) M attenuated the degree of pulmonary edema
      following acid-induced lung injury. Extravascular lung water increased to only
      180 +/- 30 microL with salmeterol treatment, compared with 296 +/- 65 microL in
      saline-treated rats 4 hrs after acid injury (p <.05). This decrease in lung water
      was accompanied by a 2.4-fold increase in the rate of alveolar fluid clearance at
      4 hrs in the salmeterol-treated group. Lung endothelial permeability, expressed
      as extravascular plasma equivalents, was reduced to 64 +/- 9 microL with
      salmeterol compared with 119 +/- 51 microL in saline-treated rats 4 hrs after
      acid injury (p <.05). CONCLUSIONS: Clinically relevant airspace concentrations of
      beta2-adrenergic agonists a) stimulate maximal cAMP-dependent airspace fluid
      clearance in normal lungs and b) reduce pulmonary edema in acid aspiration
      induced lung injury by increasing alveolar fluid clearance and decreasing
      endothelial permeability. Clinical studies are required to determine whether
      beta2-adrenergic agonists improve outcome in patients with acute lung injury.

PMID- 15241091
TI  - Impact of between-hospital volume and within-hospital volume on mortality and
      readmission rates for trauma patients in California.
AB  - OBJECTIVE: Previous research assessing the impact of between-hospital trauma
      volume (high volume centers vs. low volume centers) and outcomes has been
      inconsistent. Furthermore, previous research has not considered temporal
      variations in within-hospital volume (a center having higher than average volume
      vs. lower than average volume) as a covariate. The objective of this study was to
      determine the relationship of between-hospital and within-hospital trauma volume
      and two measures of hospital quality of care. DESIGN: Multivariable,
      hierarchical, mixed effects, logistic regression analyses of a population-based
      nonconcurrent cohort from 1995 to 1999. SETTING: Thirty-nine nonfederal
      California hospitals included in the California Patient Discharge Data Set
      designated by local Emergency Medical Services authorities as adult trauma
      centers. PATIENTS: All nonelderly adult trauma patients, 16-64 yrs (n = 54,352),
      and elderly adult trauma patients, >65 yrs (n = 47,656), admitted with an Injury
      Severity Score >9. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severity
      adjusted in-hospital mortality rate and 30-day trauma-related readmissions were
      analyzed. Among nonelderly adult patients, higher annual between-hospital trauma
      volume was not associated with mortality rate (odds ratio, 1.02 for each 100
      admissions; 95% confidence interval, 0.99, 1.06) but was associated with higher
      risk of readmission (odds ratio, 1.19 for each 100 admissions; 95% confidence
      interval, 1.13, 1.26). Among elderly adult patients, higher annual between
      hospital trauma volume was associated with lower mortality (odds ratio, 0.79 for
      each 100 admissions; 95% confidence interval, 0.71, 0.87) but was not associated
      with risk of readmission (odds ratio, 0.96 for each 100 admissions; 95%
      confidence interval, 0.90, 1.04). Higher than average monthly within-hospital
      trauma volume was associated with higher odds of readmission (odds ratio, 1.11
      for a volume deviation of ten patients per month; 95% confidence interval, 1.01,
      1.21) among elderly adult patients. CONCLUSIONS: The findings of this study in
      the context of previous research suggest that relationships between trauma volume
      and outcomes exist but depend on which patient populations are studied and how
      the data are analyzed. Furthermore, trauma centers may be subject to the
      detrimental effects of high temporal volume overextending existing services and
      capacity. Since this study found that both between-hospital volume and within
      hospital volume measures are associated with outcomes, we recommend that both
      measures be included in future volume-outcome investigations.

PMID- 15241092
TI  - Family satisfaction with family conferences about end-of-life care in the
      intensive care unit: increased proportion of family speech is associated with
      increased satisfaction.
AB  - OBJECTIVE: Family members of critically ill patients report dissatisfaction with
      family-clinician communication about withdrawing life support, yet limited data
      exist to guide clinicians in this communication. The hypothesis of this analysis
      was that increased proportion of family speech during ICU family conferences
      would be associated with increased family satisfaction. DESIGN: Cross-sectional
      study. SETTING: We identified family conferences in intensive care units of four
      Seattle hospitals during which discussions about withdrawing life support were
      likely to occur. PARTICIPANTS: Participants were 214 family members from 51
      different families. There were 36 different physicians leading the conferences,
      as some physicians led more than one conference. INTERVENTIONS: Fifty-one
      conferences were audiotaped. MEASUREMENTS: We measured the duration of time that
      families and clinicians spoke during the conference. All participants were given
      a survey assessing satisfaction with communication. RESULTS: The mean conference
      time was 32.0 mins with an sd of 14.8 mins and a range from 7 to 74 mins. On
      average, family members spoke 29% and clinicians spoke 71% of the time. Increased
      proportion of family speech was significantly associated with increased family
      satisfaction with physician communication. Increased proportion of family speech
      was also associated with decreased family ratings of conflict with the physician.
      There was no association between the duration of the conference and family
      satisfaction. CONCLUSIONS: This study suggests that allowing family members more
      opportunity to speak during conferences may improve family satisfaction. Future
      studies should assess the effect of interventions to increase listening by
      critical care clinicians on the quality of communication and the family
      experience.

PMID- 15241093
TI  - Elevated body temperature independently contributes to increased length of stay
      in neurologic intensive care unit patients.
AB  - OBJECTIVE: Elevated temperature results in worse outcome in experimental models
      of cerebral ischemia and brain trauma. In critically ill neurologic and
      neurosurgical patients, elevated body temperature is common and is associated
      with neurologic deterioration and poor outcome. We sought to determine whether,
      after controlling for age, severity of illness, and complications, elevated body
      temperature remained an important predictor of intensive care unit (ICU) and
      hospital length of stay, mortality rate, and hospital disposition in a large
      cohort of patients emergently admitted to a neurologic ICU. DESIGN: Prospectively
      collected data (demographics, diagnosis, Acute Physiology and Chronic Health
      Evaluation II score, Glasgow Coma Scale score, daily maximum temperature,
      complications, disposition) were retrospectively reviewed. SETTING: A 20-bed
      neurology/neurosurgery ICU in a tertiary care academic, level I trauma, referral
      center. SUBJECTS: From 6,759 admissions, those admitted after an elective
      procedure with length of stay < or = 1 day, those <18 yrs old, and those with
      incomplete data were excluded, leaving 4,295 patients for this analysis. First, a
      hierarchical multiple regression analysis was performed to determine whether
      elevated body temperature was an independent predictor of length of stay. Second,
      a path analysis was performed to define the relationships among elevated body
      temperature, complications, and length of stay. Finally, a matched, weighted
      sample was developed to quantify the difference in length of stay. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: We measured ICU and hospital length of stay,
      mortality rate, and discharge disposition. The presence of elevated body
      temperature was associated with a dose-dependent longer ICU and hospital length
      of stay, higher mortality rate, and worse hospital disposition. The most
      important predictor of ICU length of stay was the number of complications (beta
      =.681) followed by elevated body temperature (beta =.143). In the matched,
      weighted population, the presence of elevated body temperature was associated
      with 3.2 additional ICU days and 4.3 additional hospital days. CONCLUSION: In a
      large cohort of neurologic ICU patients, after we controlled for severity of
      illness, diagnosis, age, and complications, elevated body temperature was
      independently associated with a longer ICU and hospital length of stay, higher
      mortality rate, and worse outcome.

PMID- 15241094
TI  - Incidence and regional distribution of lung overinflation during mechanical
      ventilation with positive end-expiratory pressure.
AB  - OBJECTIVE: In patients with acute lung injury, alveolar recruitment resulting
      from positive end-expiratory pressure (PEEP) may be associated with overinflation
      of previously aerated lung regions. The aim of this study was to assess the
      incidence and regional distribution of lung overinflation resulting from
      mechanical ventilation with PEEP. DESIGN: Reanalysis with a specific software
      including a color-coding system of quantitative lung computed tomography data
      obtained in four previous prospective studies. SETTING: A 20-bed surgical
      intensive care unit of a Parisian university hospital. PATIENTS: Thirty-two
      patients with acute lung injury in whom computed tomography of the whole lung was
      obtained at zero end-expiratory pressure (ZEEP) and PEEP 15 cm H2O.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total lung recruitment was
      measured as the reaeration of poorly aerated (computed tomography attenuations
      ranging between -500 and -100 Hounsfield units) and nonaerated (computed
      tomography attenuations > or = -100 Hounsfield units) lung areas, and
      overinflation was measured as the lung volume characterized by computed
      tomography attenuations < or = -900 Hounsfield units. PEEP was associated with a
      significant alveolar recruitment (423 +/- 178 mL). Concomitantly, a lung
      overinflation of 123 +/- 138 mL was found in 14 patients (44%). In eight patients
      without chronic obstructive pulmonary disease, lung overinflation was
      predominantly found in nondependent lung regions located beneath the dome of
      diaphragm. In six patients with a past history of chronic obstructive pulmonary
      disease, PEEP increased the volume of emphysematous areas present in apical lung
      regions and produced an overinflation of nondependent lung regions located
      beneath the dome of diaphragm. CONCLUSION: Lung overinflation resulting from
      mechanical ventilation with PEEP is observed in more than one third of patients
      with acute lung injury lying supine and predominates in caudal and nondependent
      lung regions. Furthermore, in patients with a history of chronic obstructive
      pulmonary disease, PEEP markedly increases the volume of emphysematous lung
      regions.

PMID- 15241095
TI  - Mechanical ventilation in Ontario, 1992-2000: incidence, survival, and hospital
      bed utilization of noncardiac surgery adult patients.
AB  - OBJECTIVE: Mechanical ventilation is a common therapy used in caring for
      critically ill patients, but its epidemiology is poorly understood. We describe
      population-based, temporal trends in the incidence, survival, and hospital bed
      utilization of mechanically ventilated, noncardiac surgery adult patients.
      DESIGN: Retrospective, observational cohort study using linked administrative
      databases. SETTING: Province of Ontario, Canada. PATIENTS: Subjects were 150,755
      unique patients who received mechanical ventilation between 1992 and 2000.
      INTERVENTIONS: None. MEASUREMENTS: Annual measures of mechanical ventilation
      incidence, 30-day patient mortality rate, and number of mechanical ventilation
      days and inpatient days for mechanically ventilated patients as a proportion of
      total adult inpatient bed days. MAIN RESULTS: From 1992 to 2000, the crude and
      age- and gender-adjusted incidence of mechanical ventilation increased 9% (p
      <.001) and 2% (p <.027), respectively, to 217 per 100,000 adults. Crude mortality
      rate 30 days after initiation of mechanical ventilation increased from 27% to 32%
      (p <.001). Significant predictors of 30-day mortality rate (adjusted hazard
      ratio, 95% confidence interval) were calendar year (1.03, 1.02-1.03), age >80 yrs
      (2.3, 2.2-2.3), Charlson score 3+ (2.0, 2.0-2.1), and specific diagnosis. From
      1992 to 2000, the number of mechanical ventilation days and inpatient days for
      mechanically ventilated patients, as a proportion of total adult inpatient bed
      days, increased 69% and 30% (both p <.001), respectively, to 1.8% and 6.2%.
      CONCLUSIONS: There was a small, but important, increase in mechanical ventilation
      incidence and a substantial increase in the proportion of inpatient bed days used
      by mechanically ventilated patients in Ontario during the 1990s. These trends are
      important in planning for expansion of health care resources to meet the needs of
      the aging population. The increase, over time, in risk-adjusted mortality rate of
      mechanically ventilated patients is concerning and requires further
      investigation.

PMID- 15241096
TI  - New method of classifying infections in critically ill patients.
AB  - OBJECTIVE: To develop a systematic classification describing the contribution
      made by infection to the outcome from sepsis. CONTEXT: The emergence of effective
      therapies for sepsis means that accurate methods of risk assessment are of
      increasing importance. Although there are well-validated instruments for
      describing risk factors in the host, the contribution made by the infection is
      less well served. DESIGN AND METHODS: A systematic literature review of the
      English language literature published during the last 30 yrs of studies
      describing the outcome of infections, categorized by micro-organism and site of
      infection. RESULTS: We surveyed 510 published articles including 55,854 clinical
      infections, and we generated specific risk codes for bacteremia, meningitis,
      pneumonia, skin and soft tissue infections, peritonitis, and urinary tract
      infections. Both the nature of the organisms and the site of infection have a
      significant impact on survival from sepsis, and there is a significant
      interaction between them. CONCLUSION: We have described a novel approach to
      permit a better assessment of the contribution made by the infection to mortality
      in patients with sepsis or septic shock.

PMID- 15241097
TI  - The symptom burden of chronic critical illness.
AB  - OBJECTIVE: To assess self-reported symptom burden of chronic critical illness.
      DESIGN: Prospective cohort study. SETTING: Respiratory care unit for treatment of
      chronically critically ill patients at an academic, tertiary-care, urban medical
      center. PATIENTS: Fifty patients who underwent elective tracheotomy and transfer
      from an adult intensive care unit to the respiratory care unit for weaning from
      mechanical ventilation. INTERVENTIONS: Assessment of physical and psychological
      symptoms through patients' self-reports using a modification of the Condensed
      Form of the Memorial Symptom Assessment Scale. MEASUREMENTS AND MAIN RESULTS: We
      measured self-reported symptom burden, ventilator outcomes, and vital status and
      functional status at discharge and 3 and 6 months after discharge. Half of the
      patients were successfully liberated from mechanical ventilation, but most
      hospital survivors were discharged to skilled nursing facilities and more than
      half of the cohort was dead at 3 months after discharge. Seventy-two percent (36
      of 50) of patients were able to self-report symptoms during the period of
      respiratory care unit treatment. Among patients responding to symptom assessment,
      approximately 90% were symptomatic. Forty-four percent of patients reported pain
      at the highest levels. More than 60% reported psychological symptoms at these
      levels, and approximately 90% of patients reported severe distress due to
      difficulty communicating. CONCLUSIONS: Physical and psychological symptom
      distress is common and severe among patients receiving treatment for chronic
      critical illness. The majority of these patients die soon after hospital
      discharge. Given the level of distress in our study patients and the high
      mortality rate that we and others have observed, greater attention should be
      given to relief of pain and other distressing symptoms and to assessment of
      burdens and benefits of treatment for the chronically critically ill.

PMID- 15241098
TI  - The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool
      for distinguishing necrotizing fasciitis from other soft tissue infections.
AB  - OBJECTIVE: Early operative debridement is a major determinant of outcome in
      necrotizing fasciitis. However, early recognition is difficult clinically. We
      aimed to develop a novel diagnostic scoring system for distinguishing necrotizing
      fasciitis from other soft tissue infections based on laboratory tests routinely
      performed for the evaluation of severe soft tissue infections: the Laboratory
      Risk Indicator for Necrotizing Fasciitis (LRINEC) score. DESIGN: Retrospective
      observational study of patients divided into a developmental cohort (n = 314) and
      validation cohort (n = 140) SETTING: Two teaching tertiary care hospitals.
      PATIENTS: One hundred forty-five patients with necrotizing fasciitis and 309
      patients with severe cellulitis or abscesses admitted to the participating
      hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The developmental
      cohort consisted of 89 consecutive patients admitted for necrotizing fasciitis.
      Control patients (n = 225) were randomly selected from patients admitted with
      severe cellulitis or abscesses during the same period. Hematologic and
      biochemical results done on admission were converted into categorical variables
      for analysis. Univariate and multivariate logistic regression was used to select
      significant predictors. Total white cell count, hemoglobin, sodium, glucose,
      serum creatinine, and C-reactive protein were selected. The LRINEC score was
      constructed by converting into integer the regression coefficients of
      independently predictive factors in the multiple logistic regression model for
      diagnosing necrotizing fasciitis. The cutoff value for the LRINEC score was 6
      points with a positive predictive value of 92.0% and negative predictive value of
      96.0%. Model performance was very good (Hosmer-Lemeshow statistic, p =.910); area
      under the receiver operating characteristic curve was 0.980 and 0.976 in the
      developmental and validation cohorts, respectively. CONCLUSIONS: The LRINEC score
      is a robust score capable of detecting even clinically early cases of necrotizing
      fasciitis. The variables used are routinely measured to assess severe soft tissue
      infections. Patients with a LRINEC score of > or = 6 should be carefully
      evaluated for the presence of necrotizing fasciitis.

PMID- 15241099
TI  - Effect of prolongation of expiratory time on dynamic hyperinflation in
      mechanically ventilated patients with severe asthma.
AB  - OBJECTIVE: To assess the effect of a decrease in respiratory rate on dynamic
      hyperinflation, as determined by changes in plateau airway pressure, in patients
      with status asthmaticus whose baseline minute ventilation approximated 10 L/min.
      DESIGN: Observational descriptive study. SETTING: Medical intensive care unit.
      PATIENTS: Twelve patients with severe asthma mechanically ventilated in the
      assist control mode with a tidal volume of 613 +/- 100 mL and an inspiratory flow
      rate of 79 +/- 4 L/min. INTERVENTIONS: A decrease in respiratory rate from 18 to
      12 and 6 breaths/min. MEASUREMENTS AND MAIN RESULTS: Plateau airway pressure
      decreased by approximately 2 cm H2O (25.4 +/- 2.8 vs. 23.3 +/- 2.6 cm H2O, p
      <.01) when respiratory rate was decreased from 18 to 12 breaths/min (increase in
      expiratory time 1.7 secs) and by a similar amount (23.3 +/- 2.6 vs. 21.3 +/- 2.9
      cm H2O, p <.01) when respiratory rate was decreased from 12 to 6 breaths/min
      (increase in expiratory time 5 secs). Peak airway pressure was similar at the
      three respiratory rates (66.8 +/- 8.7 vs. 66.4 +/- 9.5 vs. 67.8 +/- 11.1 cm H2O
      at 18, 12, and 6 breaths/min, respectively). End-expiratory flow rates (n = 7)
      were 61.4 +/- 12.6, 38.6 +/- 4.5, and 23.1 +/- 5.8 mL/sec at respiratory rates of
      18, 12, and 6 breaths/min, respectively. CONCLUSIONS: Prolongation of expiratory
      time decreases dynamic hyperinflation in patients with status asthmaticus, as
      evidenced by a reduction in plateau airway pressure, but the magnitude of this
      effect is relatively modest when baseline minute ventilation is < or = 10 L/min,
      because of the low end-expiratory flow rates. Since flow progressively decreases
      throughout expiration, the reduction in dynamic hyperinflation resulting from a
      given prolongation of expiratory time will depend on the baseline respiratory
      rate (i.e., less reduction in dynamic hyperinflation at a lower respiratory
      rate). Changes in peak airway pressure may not always reflect the changes in
      dynamic hyperinflation that result from prolongation of expiratory time.

PMID- 15241100
TI  - Exhaled tidal volume overestimation in mechanically ventilated patients with
      large cardiogenic oscillation.
AB  - OBJECTIVES: In postcardiac surgery patients, we often noticed that monitored
      tidal volumes exceeded the ventilator settings. We investigated whether
      cardiogenic oscillation causes overestimation of tidal volume. DESIGN:
      Prospective, observational, clinical study. SETTING: Surgical intensive care unit
      in a national heart institute. PATIENTS: Eight postcardiac surgery patients (age
      13-70). INTERVENTIONS: Patients were paralyzed and received flow-triggered volume
      controlled ventilation with a tidal volume of 10 mL/kg. In random order, two
      types of ventilator (Bird 8400 STi and Servo-300) and two respiratory rates (5
      and 10 breaths/min) were applied to each patient via a disposal ventilatory
      circuit and heat-and-moisture exchanger. For each ventilator, we adjusted the
      flow-triggering sensitivity to prevent autotriggering due to cardiogenic
      oscillation: 10 L/min for the Bird 8400 STi and green zone for the Servo-300.
      MEASUREMENTS AND MAIN RESULTS: The magnitude of cardiogenic oscillation during
      mechanical ventilation was defined as peak expiratory flow fluctuation at end
      expiration. We recorded tidal volume using the monitoring devices on the
      ventilators and calculated the discrepancy from the set tidal volume. Cardiogenic
      oscillation was significantly greater with the Bird 8400STi (4.0 +/- 1.8 L/min)
      than with the Servo-300 (1.7 +/- 0.8 L/min). With the Bird 8400 STi, the
      discrepancy between monitored tidal volume and set tidal volume ranged from 15 to
      260 mL when the respiratory rate was 5 breaths/min and from -9 to 75 mL at 10
      breaths/min; there was a linear correlation between the overestimation of tidal
      volume and the magnitude of cardiogenic oscillation. In contrast, with the Servo
      300, the discrepancy was relatively small (-36 to 14 mL). CONCLUSIONS: In
      mechanically ventilated patients with large cardiogenic oscillation, exhaled
      tidal volume is overestimated on at least one model of ventilator.

PMID- 15241101
TI  - Accuracy of transpulmonary thermodilution versus gravimetric measurement of
      extravascular lung water.
AB  - OBJECTIVE: Pulmonary edema is a severe and often life-threatening condition. The
      diagnosis of pulmonary edema and its quantification have great clinical
      significance and yet can be difficult. A new technique based on thermodilution
      measurement using a single indicator has recently been developed (PiCCO, Pulsion
      Medical Systems, AG Germany). This method allows the measurement of extravascular
      lung water and thus can quantify degree of pulmonary edema. The technique has not
      been compared with a gold standard, gravimetric measurement of extravascular lung
      water. Therefore, the objective of this study was to determine the ability of
      extravascular lung water measurement with the PiCCO to reflect the extravascular
      lung water as measured with a gravimetric technique in a dog model of pulmonary
      edema. DESIGN: Prospective, randomized animal study. SETTING: A university animal
      research laboratory. SUBJECTS: Fifteen mongrel dogs (n = 5/group) weighing 20-30
      kg. INTERVENTIONS: The dogs were anesthetized and mechanically ventilated. Five
      dogs served as controls; in five dogs hydrostatic pulmonary edema was induced
      using inflation of a left atrial balloon combined with fluid administration to
      maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary
      edema was induced by intravenous injection of oleic acid. After a period of
      stabilization in a state of pulmonary edema, extravascular lung water was
      measured with the PiCCO monitor. The animals were then killed, and extravascular
      lung water was measured using a gravimetric technique. MEASUREMENTS AND MAIN
      RESULTS: There was a very close (r =.967, p <.001) relationship between
      transpulmonary thermodilution and gravimetric measurements. The measurement with
      the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric
      measurement. CONCLUSIONS: Measurement of extravascular lung water using
      transpulmonary thermodilution with a single indicator is very closely correlated
      with gravimetric measurement of lung water in both increased permeability and
      hydrostatic pulmonary edema.

PMID- 15241102
TI  - Treatment of hypotension in pigs with an inspiratory impedance threshold device:
      a feasibility study.
AB  - OBJECTIVE: An inspiratory impedance threshold device was evaluated in
      spontaneously breathing animals with hypotension to determine whether it could
      help improve systemic arterial pressures when fluid replacement was not
      immediately available. DESIGN: Prospective, randomized. SETTING: Animal
      laboratory. SUBJECTS: Thirty-nine female farm pigs (weight, 28-33 kg).
      INTERVENTIONS: A total of 39 anesthetized spontaneously breathing pigs were
      treated with an impedance threshold device, with cracking pressures from 0 to -20
      cm H2O. Four separate experimental protocols were performed: protocol A, in which
      the hemodynamics of seven pigs were examined during application of an impedance
      threshold device at various levels of inspiratory impedance (-5, -10, -15, and 
      20 cm H(2)O), both before and after a severe, controlled hemorrhage to a systolic
      blood pressure of 50 - 55 mm Hg; protocol B, in which nine pigs bled to systolic
      blood pressure of 50 -55 mm Hg were treated with an impedance threshold device
      set at -12 cm H2O and were compared with nine others treated with a sham device;
      protocol C, in which the effects of the impedance threshold device on mixed
      venous gases were measured in seven hemorrhaged pigs; and protocol D, in which
      the effects of the impedance threshold device on cardiac output in seven
      hemorrhaged pigs were measured. METHODS AND MAIN RESULTS: During initial studies
      with both normovolemic and hypovolemic pigs, sequential increases in inspiratory
      impedance resulted in a significant increase in systolic blood pressure, whereas
      diastolic left ventricular and right atrial pressures decreased significantly and
      proportionally to the level of impedance. When comparing the sham vs. active
      impedance threshold device (-12 cm H(2)O) in hypotensive pigs, systolic blood
      pressure (mean +/- sem) with active impedance threshold device treatment
      increased from 70 +/- 2 mm Hg to 105 +/- 4 mm Hg (p <.01). Pressures in the
      control group remained at 70 +/- 4 mm Hg (p <.01). Cardiac output increased by
      nearly 25% (p <.01) with the active impedance threshold device when calculated
      using the mixed gas equation and when determined by thermodilution. CONCLUSIONS:
      These studies demonstrate that it is feasible to use a device that creates
      inspiratory impedance in spontaneously breathing normotensive and hypotensive
      pigs to increase blood pressure and enhance cardiopulmonary circulation in the
      absence of immediate fluid resuscitation. Further studies are needed to evaluate
      the potential long-term effects and limitations of this new approach to treat
      hypovolemic hypotension.

PMID- 15241103
TI  - Ventilation strategy affects cytokine release after mesenteric ischemia
      reperfusion in rats.
AB  - OBJECTIVE: To evaluate the impact of different ventilation modalities on lung and
      plasma concentrations of cytokines in a model of secondary lung inflammation,
      mesenteric ischemia-reperfusion, in rats. DESIGN: Prospective, randomized,
      controlled animal study. SETTING: Research laboratory of a university. SUBJECTS:
      Sixty-four male adult Wistar rats weighing 320-380 g. INTERVENTIONS: Eight groups
      were studied. Two groups underwent no surgical procedure: They were either not
      ventilated or ventilated with an injurious modality consisting of 30 mL/kg tidal
      volume (Vt) without positive-end expiratory pressure (PEEP). Animals of the other
      groups underwent laparotomy with or without 2-hr mesenteric ischemia followed by
      4 hrs of reperfusion during which the rats were mechanically ventilated.
      Ventilation modalities were conventional (tidal volume 10 mL/kg, PEEP 3 cm H2O),
      protective (6 mL/kg, 6 cm H(2)O), or injurious (tidal volume 30 mL/kg and no
      PEEP). Rats were killed by exsanguination, and their lungs were excised and
      homogenized in buffer. Supernatants of lung homogenates and plasmas were stored
      at -80 degrees C for subsequent measurements. MEASUREMENTS AND MAIN RESULTS:
      Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, macrophage
      inhibitory protein 2, and interleukin-10 were determined in lung supernatants and
      plasmas with a rat-specific enzyme-linked immunosorbent assay. Lung and plasma
      cytokine concentrations were not significantly different between rats ventilated
      with the injurious modality only and nonventilated rats. Lung and plasma cytokine
      concentrations were higher in rats that had undergone mesenteric ischemia
      reperfusion than in rats with laparotomy only, whatever ventilation modality.
      Lung and plasma cytokine concentrations were higher in these rats after the
      injurious ventilation modality than after the other modalities. CONCLUSION: This
      study shows that an injurious ventilation does not produce significant in vivo
      release of cytokines in intact animals but promotes the release of pro- and anti
      inflammatory cytokines in an inflammatory context.

PMID- 15241104
TI  - Evaluation of protein C and other biomarkers as predictors of mortality in a rat
      cecal ligation and puncture model of sepsis.
AB  - OBJECTIVE: To evaluate protein C and other factors associated with the septic
      response as predictors of mortality in a clinically relevant animal model of
      sepsis. DESIGN: Laboratory investigation. SETTING: Eli Lilly and Company
      discovery research laboratory. SUBJECTS: Forty female Sprague Dawley rats
      weighing 245-265 g. INTERVENTIONS: Polyethylene catheters were surgically
      implanted into the femoral vein and sepsis was induced by cecal ligation and
      puncture (CLP). A solution of 5% dextrose in 0.9 % saline was continuously
      infused via femoral catheters immediately following surgery. Blood sampling was
      done before surgery and at 6 and 20 hrs after surgery. Rats were then monitored
      for survival out to 4 days. MEASUREMENTS AND MAIN RESULTS: Blood collections were
      used to measure blood glucose, bacteremia, plasma protein C, D-dimer, hormones,
      chemokines, cytokines, and myoglobin (as a marker of organ damage). Mortality was
      categorized into three groups: early death (before 30 hrs post-CLP), late death
      (after 30 hrs post-CLP), and survivors (96 hrs post-CLP). Compared with
      survivors, early death rats had statistically significant differences in 30
      variables indicative of severe inflammation, coagulopathy, and muscle damage
      including less bacterial clearance, hypoglycemia, lower plasma protein C, higher
      plasma D dimer, higher plasma cytokine/ chemokines, and higher plasma myoglobin
      concentrations. Twenty variables had a moderate to strong correlation with time
      of death. Receiver operator characteristic curves generated from a simple
      logistic regression model indicated that KC and macrophage inflammatory protein
      2, rodent homologues of the human growth related oncogene CXC chemokine family,
      and protein C were the best predictors of mortality in this model. CONCLUSIONS:
      The data from this study indicate that an early decrease in protein C
      concentration predicts poor outcome in a rat sepsis model. The data further
      indicate that increases in the CXC chemokines macrophage inflammatory protein-2
      and KC precede poor outcome.

PMID- 15241105
TI  - Relationship between brain perfusion computed tomography variables and cerebral
      perfusion pressure in severe head trauma patients.
AB  - OBJECTIVE: To compare brain perfusion-computed tomography (CT) results with
      invasive cerebral perfusion pressure (CPP) monitoring in severe head trauma
      patients. DESIGN: Prospective cohort study. SETTING: Emergency room and surgical
      intensive care unit of our hospital. PATIENTS: Sixty-one severe head trauma
      patients. INTERVENTIONS: We prospectively collected 103 perfusion-CT examinations
      with simultaneous measurement of mean arterial pressure and intracranial
      pressure, affording calculation of CPP. The statistical relationship between
      perfusion-CT results and the corresponding CPP values was evaluated using
      Wilcoxon (Mann-Whitney) and generalized F-tests. The functional outcome of the 61
      patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome
      Scale score and compared between groups using Fisher's exact tests. MEASUREMENTS
      AND MAIN RESULTS: Perfusion-CT enabled us to distinguish between two groups of
      patients. Within each group, a significant correlation (p <.001) between the CPP
      values and the corresponding perfusion-CT results was demonstrated. There was
      also a significant correlation (p <.001) between the CPP values and the extent of
      the abnormal perfusion-CT areas (R up to.817). The first group was characterized
      by a weak dependence of perfusion-CT results on the corresponding CPP values (low
      slope) and the second group by a strong dependence (steep slope). These groups
      were interpreted as having preserved (or pseudo) and impaired cerebral vascular
      autoregulation, respectively. The functional outcome was better in the second
      group of patients. CONCLUSIONS: Intermittent perfusion-CT measurements plus
      continuous CPP measurement provide more information than continuous CPP alone.
      Perfusion-CT gives unique information regarding regional heterogeneity of brain
      perfusion. It might allow clinicians to distinguish between patients with
      preserved auto-regulation (or pseudoautoregulation) and those with impaired
      autoregulation and could therefore guide interpretation of CPP measurements and
      therapy.

PMID- 15241106
TI  - Rationing critical care beds: a systematic review.
AB  - OBJECTIVE: Rationing critical care beds occurs daily in the hospital setting. The
      objective of this systematic review was to examine the impact of rationing
      intensive care unit beds on the process and outcomes of care. DATA SOURCE: We
      searched MEDLINE (1966-2003), CINAHL (1982-2003), Ovid Healthstar (1975-2003),
      EMBASE (1980-2003), Scisearch (1980-2003), the Cochrane Library, PUBMED related
      articles, personal files, abstract proceedings, and reference lists. STUDY
      SELECTION: We included studies of seriously ill patients considered for admission
      to an intensive care unit bed during periods of reduced availability. We had no
      restriction on study design. Studies were excluded if rationing was performed
      using a scoring system or protocol and if cost-effectiveness was the only
      outcome. DATA EXTRACTION: In duplicate and independently, we performed data
      abstraction and quality assessment. DATA SYNTHESIS: We included ten observational
      studies. Hospital mortality rate was increased in patients refused intensive care
      unit admission vs. those admitted (odds ratio, 3.04; 95% confidence interval,
      1.49-6.17). Factors associated with both intensive care unit bed refusal and
      increased mortality rate were increased age, severity of illness, and medical
      diagnosis. When intensive care unit beds were reduced, admitted patients were
      sicker, were less often admitted primarily for monitoring, and had a shorter
      intensive care unit length of stay, without other observed adverse effects.
      CONCLUSIONS: These studies suggest that patients who are perceived not to benefit
      from critical care are more often refused intensive care unit admission; refusal
      is associated with an increased risk of hospital death. During times of decreased
      critical bed availability, several factors, including age, illness severity, and
      medical diagnosis, are used to triage patients, although their relative
      importance is uncertain. Critical care bed rationing requires further
      investigation.

PMID- 15241107
TI  - The surviving sepsis guidelines: "lost in translation".

PMID- 15241108
TI  - The surviving sepsis guidelines: not another "groundhog day".

PMID- 15241109
TI  - Ethyl pyruvate: a simple solution?

PMID- 15241110
TI  - Delay of neutrophil apoptosis can exacerbate inflammation in sepsis patients:
      cellular mechanisms.

PMID- 15241111
TI  - beta(2)-Agonists for treatment of pulmonary edema: ready for clinical studies?

PMID- 15241112
TI  - When will it be clear?

PMID- 15241113
TI  - On speaking less and listening more during end-of-life family conferences.

PMID- 15241114
TI  - Acute brain injury: if hypothermia is good, then is hyperthermia bad?

PMID- 15241115
TI  - Think globally and act regionally: how do we use the computed tomography scan
      assessment of lung inflation in acute respiratory distress syndrome?

PMID- 15241116
TI  - Affordable health care for all Canadians?

PMID- 15241117
TI  - Sepsis: let's go back to the infectious process.

PMID- 15241118
TI  - How will we respond to chronic critical illness?

PMID- 15241119
TI  - The laboratory risk indicator for necrotizing fasciitis (LRINEC) score: useful
      tool or paralysis by analysis?

PMID- 15241120
TI  - Predicting mortality from sepsis: is protein C a true crystal ball?

PMID- 15241121
TI  - Perfusing the brain after traumatic brain injury: what clinical index should we
      follow?

PMID- 15241122
TI  - Access to critical care: medical rationing of a public right or privilege?

PMID- 15241124
TI  - Administration of nitric oxide synthase inhibitor 546C88 in septic shock.

PMID- 15241125
TI  - Stress ulcer prophylaxis.

PMID- 15241126
TI  - Central venous and mixed venous oxygen saturations in the surviving sepsis
      campaign guidelines.

PMID- 15241128
TI  - Quality of life after mechanical ventilation.

PMID- 15241129
TI  - Paralysis during mechanical ventilation in acute respiratory distress syndrome:
      back to the future?

PMID- 15241131
TI  - Use of intensive care at the end of life in the United States.

PMID- 15241136
TI  - Editorial: Why ankle replacement?

PMID- 15241133
TI  - End-of-life planning for the elderly.

PMID- 15241137
TI  - An artificial ankle joint.

PMID- 15241138
TI  - Midterm results of the Salto Total Ankle Prosthesis.
AB  - The Salto Total Ankle Prosthesis is noncemented with mobile bearings and is
      characterized by an anatomic design and a dual Ti-HA coating. Between 1997 and
      2000, 98 consecutive Salto prostheses were implanted. At last followup, two
      patients were deceased, one patient was lost to followup, and two prostheses were
      removed in two patients. Ninety-three implants in 91 patients were available with
      a mean followup of 35 months (range, 24-68 months). Survivorship at 68 months,
      with the end point implant removal, then was 98% (favorable scenario) to 94.9%
      (unfavorable scenario). The American Orthopaedic Foot and Ankle Society score was
      32.3 points preoperatively and 83.1 points at followup. Seventy-two patients are
      pain-free, 54 patients walk unlimited distances, and 25 patients have limitation
      but walk more than 1 km. Sixty-seven patients have no limp but seven need walking
      aids. Fifty-eight patients can walk on tiptoes, 49 patients can walk on uneven
      ground, 14 patients can run, 76 patients ascend stairs normally, and 63 patients
      descend stairs normally. Range of motion as measured on stress radiographs
      improved from 15.2 degrees preoperatively to 28.3 degrees at followup.
      Preliminary results of the Salto prosthesis are encouraging and validate the
      concept of anatomic replacement.

PMID- 15241139
TI  - Twenty-year evaluation of cementless mobile-bearing total ankle replacements.
AB  - Two consecutive series of patients who had cementless, porous-coated, congruent
      contact, mobile-bearing total ankle replacements were evaluated during a 20-year
      interval using the New Jersey Orthopaedic Hospital ankle scoring scale to
      determine clinical outcome and overall implant survivorship with revision as an
      end point. The initial series of 38 patients (40 ankle replacements) using a
      shallow-sulcus design had diagnoses of: osteoarthritis, seven (17.5%); rheumatoid
      arthritis, nine (22.5%); posttraumatic arthritis, 21 (52.5%); and failed fusion,
      three (7.5%). Clinical results after 2-20 years, (mean, 12 years) were 28 (70%)
      good to excellent, two (5%) fair, and 10 (25%) poor. Postoperative ankle motion
      ranged from 10 degrees-47 degrees total arc (mean, 25 degrees total arc). The 20
      year overall survivorship for the shallow-sulcus design was 74.2%. A second
      series of 74 patients (75 ankle replacements) using a deep-sulcus design had
      diagnoses of: osteoarthritis, eight (11%); rheumatoid arthritis, nine (12%);
      osteonecrosis, three (4%); and posttraumatic arthritis, 55 (73%). Clinical
      results after 2-12 years, (mean 5 years) were 66 (88%) good to excellent, four
      (5%) fair, and five (7%) poor. Postoperative ankle motion ranged from 10 degrees
      50 degrees total arc (mean, 29 degrees total arc). The 12-year overall
      survivorship for the deep-sulcus design was 92%.

PMID- 15241140
TI  - Accurate measurement of ankle range of motion after total ankle arthroplasty.
AB  - There is no standardized method reported in the literature to measure ROM of the
      ankle after a total ankle arthroplasty, which limits the possibility to compare
      results from the various ankle designs. It seems that most of the measurements
      are a combination of ankle and midfoot motion, not the tibiotalar joint. A
      protocol was developed to accurately measure the true tibiotalar and midfoot
      motion before and after an ankle replacement. Lateral radiographs were taken of
      the ankle with the patient in a weightbearing position, and measurements were
      done along fixed landmarks. In this study, the tibiotalar, midfoot, and combined
      ROM were measured preoperative and 1 year postoperative in a standardized,
      reproducible fashion. The preoperative tibiotalar ROM was 18.5 degrees and
      combined ankle and midfoot motion 25.1 degrees. The true tibiotalar motion after
      an Agility total ankle arthroplasty was 23.4 degrees, and the combined ankle and
      midfoot motion was 31.3 degrees. The average improvement in ROM in the tibiotalar
      joint was approximately 5 degrees, and combined ROM was 6.1 degrees. Preoperative
      ROM proved to be the main factor determining the eventual postoperative ROM. It
      is possible to accurately measure the true ankle and the midfoot motion and those
      measurements should be used when reporting on the results of ankle replacements.
      Total ankle arthroplasty resulted in a statistically significant, but clinically
      less than expected, increase in ROM.

PMID- 15241141
TI  - Total ankle replacement in patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis commonly experience involvement of the ankle
      and hindfoot. Severe pain and functional limitations may develop as a result of
      tibiotalar arthritis, requiring surgical treatment. The advantages of total ankle
      arthroplasty over ankle arthrodesis include preservation of motion and decreased
      stresses on the midfoot and subtalar joints. Previous experience with early
      design ankle replacements revealed high complication rates and as much as 75% of
      component loosening. Modern ankle implants have been designed to achieve
      uncemented fixation with less articular constraint. Patients with rheumatoid
      arthritis who had total ankle replacement using two different types of second
      generation ankle implants were examined clinically and radiographically. The
      average postoperative American Orthopaedic Foot and Ankle Society ankle-hindfoot
      score was 81 of a possible 100, at a mean of 6.4 years after surgery.
      Radiographically, 88.5% of implants were stable without evidence of subsidence at
      a mean of 6.3 years. Three tibial components had subsided at an average of 7
      years. There was evidence of tibial osteolysis with the Buechel Pappas Low
      Contact Stress implant in 11.5% of patients. Total ankle replacement in patients
      with rheumatoid arthritis, using a second-generation prosthesis, can provide
      reliable relief of pain and good functional results at intermediate-term
      followup, although the incidence of osteolysis warrants close followup.

PMID- 15241142
TI  - Mobility of the human ankle and the design of total ankle replacement.
AB  - Our prior research has shown that currently available total ankle implants fail
      to restore physiologic ankle mobility. Most of the modern mobile-bearing designs
      that feature a flat tibial component and a talar component with anatomic
      curvature in the sagittal plane function nonphysiologically with the natural
      ligament apparatus. To establish a more natural relationship between the
      implanted components and the retained ankle ligaments, we have developed a new
      design. According to our prior research, we suggest that physiologic ankle
      mobility is reproduced best with a design featuring a spherical convex tibial
      component, a talar component with radius of curvature in the sagittal plane
      longer than that of the natural talus, and a fully conforming meniscal component.
      Our preliminary observations in trial implantation and in a few patients suggest
      that while reproducing physiologic ankle mobility, the new design is capable of
      maintaining complete congruence at the two articulating surfaces of the meniscal
      bearing over the entire motion arc, with the prospect of minimizing wear of this
      component.

PMID- 15241143
TI  - Scandinavian total ankle replacement: a 3.7-year average followup of 65 patients.
AB  - The purpose of the current prospective study was to determine the midterm results
      of 68 total ankle replacements with the Scandinavian Total Ankle Replacement
      (S.T.A.R.) prosthesis. The 65 patients (34 women and 31 men; mean age at surgery,
      56.1 years [range, 22-85 years]) were assessed clinically and radiologically
      after 3.7 years (range, 2.4-6.2 years). Thirty-five patients (54%) were totally
      pain-free. The overall clinical score was graded as excellent or good in 67
      ankles. The American Orthopaedic Foot and Ankle Society hindfoot score improved
      from 24.7 points (range, 3-44 points) preoperatively to 84.3 points (range, 44
      100 points) at followup. Three patients (three ankles, 4.4%) had a ballooning
      bone lysis on the tibial side. Despite prophylaxis, periarticular hypertrophic
      bone formation was seen in 43 ankles (63%; 42 patients), associated with a
      decrease of dorsiflexion and plantar flexion. Nine ankles (13%; nine patients)
      had revision surgery because of problems with the components and 14 ankles (21%;
      14 patients) had secondary or additional operations. All revision or secondary
      surgeries were successful, and no ankle had to be converted to an ankle
      arthrodesis. The early experience with the S.T.A.R. ankle implant is encouraging,
      although we have encountered more complications and potential problems than
      previously reported.

PMID- 15241144
TI  - The HINTEGRA ankle: rationale and short-term results of 122 consecutive ankles.
AB  - The HINTEGRA ankle was developed as an attempt to specifically address the needs
      of minimal bone resection, extended bone support, proper ligament balancing, and
      minimal contact stresses within and around the prosthesis. The purpose of this
      study was to determine the short-term results in a consecutive series of 116
      patients (122 ankles). Preoperative diagnoses were posttraumatic osteoarthrosis
      in 91 ankles (75%), primary osteoarthrosis in 16 ankles (13%), and systemic
      arthritis in 15 ankles (12%). Eight ankles had to be revised. Four were revised
      because of loosening of at least one component; one because of dislocation of the
      meniscus; and three for other reasons. All revisions were successful. After an
      average of 18.9 months (range, 1-3 years), 84% of patients were satisfied, and
      the clinical result was rated as good or excellent in 82% of the cases. The
      American Orthopaedic Foot and Ankle Society hindfoot score improved from 40
      points preoperatively to 85 points at followup. Eighty-three ankles (68%) were
      completely pain-free. The average range of motion clinically was 39 degrees
      (range, 15 degrees-55 degrees) and under fluoroscopy (true ankle motion) it was
      37 degrees (range, 7 degrees-62 degrees). Radiographically, the tibial component
      was stable in all ankles, and no tilting of the component occurred since surgery.
      However, migration of the talar component was observed in two ankles. The concept
      of minimal bone resection and wide bony support was shown to be successful on the
      tibial and talar sides. Obtained function, pain relief, and patient satisfaction
      were promising and, compared with other devices, the results mostly were
      superior. This may support the idea that anatomic-shaped surfaces, as is the case
      in the HINTEGRA ankle, may be successful in total ankle replacement.

PMID- 15241145
TI  - Ankle arthroplasties generate wear particles similar to knee arthroplasties.
AB  - Second-generation total ankle arthroplasties have encouraging medium-term
      results, but the wear of the joint materials is of concern. The aim of the
      current study was to examine and compare the size, shape, and concentration of
      polyethylene particles in synovial fluid with total ankle arthroplasties and
      established posterior-stabilized total knee arthroplasties. Synovial fluid was
      obtained from 15 patients with well-functioning total ankle arthroplasties and 11
      patients with posterior-stabilized total knee arthroplasties at least 6 months
      after surgery. Polyethylene particles were isolated and analyzed using scanning
      electron microscopy. Particle size (equivalent circle diameter) in ankles was
      0.81 +/- 0.09 microm (mean +/- standard error) and in knees was 0.78 +/- 0.08
      microm. Particle shape (aspect ratio) in ankles was 1.57 +/- 0.04 and in knees
      was 2.30 +/- 0.22. The particle concentration was 1.02 +/- 0.43 x 10/mL in ankles
      and 1.13 +/- 0.56 x 10/mL in knees, and the particle concentration and size in
      total ankle arthroplasties were similar to those in total knee arthroplasties.
      Total ankle arthroplasties generated significantly rounder particles than total
      knee arthroplasties. These data suggest that the long-term result of total ankle
      arthroplasty should be as good as posterior-stabilized total knee arthroplasties
      in terms of polyethylene wear and the prevalence of osteolysis.

PMID- 15241146
TI  - Scandinavian Total Ankle Replacement (STAR).
AB  - Fifty-eight patients with either rheumatoid arthritis or osteoarthritis were
      treated with meniscal-bearing ankle prostheses. The concept was to mobilize,
      align, and stabilize the ankle before resurfacing it. Cement was used for
      prostheses fixation in 33 patients (1986-1989) and 25 patients had fixation
      without cement (1990-1995). All patients in one prospective series were followed
      up yearly with radiographs and with a clinical scoring system giving a maximum of
      100 points. This allowed for a patient-controlled prospective study. No patients
      were lost to followup. The only detectable difference in the treatment was the
      fixation mode. For the purpose of comparing patients with cemented and uncemented
      prostheses, the patients who had surgery between 1986 and 1989 were not followed
      up after 1997, and patients who had surgery between 1990 and 1995 were not
      followed up after 2002. The mean followup was 9.4 years. Failure was defined as
      prosthesis revision or change to arthrodesis for any reason. In the cemented
      group, nine of 33 patients had revision surgery or fusion. In the uncemented
      group, one of 25 patients had revision surgery. Survivorship analysis for 12
      years based on life tables showed a 70% survival rate (confidence limit, 60.3
      78.5) for the cemented group and 95.4% survival rate (confidence limit, 91.0
      99.9) for the uncemented group. The average clinical scores at the latest
      followup were 74.2 +/- 19.3 for the cemented group and 91.9 +/- 7.4 points for
      the uncemented group. Therefore, unconstrained meniscal-bearing ankle prostheses
      should be uncemented.

PMID- 15241147
TI  - Takedown of ankle fusion and conversion to total ankle replacement.
AB  - The painful ankle arthrodesis is an unsolved clinical problem. In many cases,
      transtibial amputation may be the best option for functional recovery. Recent
      reports of early success with second generation ankle implants show takedown of
      the problematic ankle fusion and conversion to total ankle arthroplasty may be an
      alternative to amputation. This study is a retrospective review of 23 ankles in
      22 patients scheduled to have this procedure. Four patients were lost to
      followup, leaving 19 ankles in 18 patients at an average followup of 39 months.
      Three patients chose to have an amputation because of continued pain. In the
      remaining 16 ankles, the mean AOFAS ankle-hind foot outcome score improved from
      42-68. Patients who had a clear source of pain with the ankle arthrodesis (such
      as subtalar arthrosis) had a better result than patients without a clear source
      of pain. All the patients who had the lateral malleolus resected during previous
      arthrodesis had complicated courses after arthroplasty. For patients with a
      definable source of pain and who have not had previous malleolar resection,
      conversion of a failed ankle arthrodesis to total ankle arthroplasty may be a
      viable alternative to amputation.

PMID- 15241148
TI  - Biomechanics of and research challenges in uncemented total ankle replacement.
AB  - Only limited data are available currently on the clinical performance of
      uncemented total ankle replacements. Even so, various complications, notably
      loosening and/or migration of the talar and/or tibial components, already have
      been seen. Nonetheless, the current consensus is that, in all likelihood,
      uncemented total ankle prostheses will continue to be implanted in some patients.
      Therefore, it is important that future designers of this prosthesis be conversant
      with all the requirements that a design must fulfill, be aware of the various
      features of second-generation designs that were introduced to address problems
      seen in implanted cemented first-generation replacement designs, be knowledgeable
      about the in vivo performance, to date, of uncemented second-generation total
      ankle replacement designs and how features of a design may impact its
      performance, and be cognizant of the gaps and/or controversies in the literature
      and the extent to which they could be addressed through focused research. All of
      these four aspects, which have been treated inadequately in the literature, are
      treated in detail in the current review, with the hope that the review will serve
      as a primer for those involved in designing the next generation of uncemented
      total ankle replacements. Thirteen design requirements, including kinematics,
      kinetics, and stability aspects, are described. Various features of three second
      generation designs are described. For three second-generation designs, the
      relationship between their estimated in vivo performance and the extent of joint
      resurfacing needed to implant them is presented. Among the seven future research
      areas discussed are design, fabrication, and validation of an ankle simulator,
      and development of a set of standardized biomechanical tests.

PMID- 15241149
TI  - Ankle arthroplasty with preoperative coronal plane deformity: short-term results.
AB  - The treatment of coronal plane deformity during total ankle arthroplasty is
      understood poorly. This study tests the hypotheses that preoperative coronal
      plane malalignment and incongruence of the ankle can be corrected and maintained
      for 2 years with total ankle replacement, and that factors can be identified that
      place ankles at risk of having progressive edge-loading develop. Of 86
      consecutive patients who had total ankle replacement, 35 had preoperative coronal
      plane alignment > or =10 degrees. Lateral ligament reconstruction was done in
      seven patients and superficial deltoid release was done in four patients at the
      time of ankle replacement. Ankles with talar and tibial deformities improved
      talar and tibial alignment toward a neutral weightbearing axis postoperatively.
      Ankles with only a talar deformity improved the talar alignment toward a neutral
      weightbearing axis postoperatively. No changes in alignment were shown during the
      subsequent 2 years. Postoperative ankle articulations were congruent. Patients
      with preoperative incongruent joints are 10 times more likely to have progressive
      edge-loading develop than patients with congruent joints. Surgeons must be
      attentive to coronal plane alignment during and after ankle replacement. Longer
      followup is needed to assess the longevity of the correction and the impact of
      minor malalignment on implant wear.

PMID- 15241150
TI  - Malleolar fracture after total ankle arthroplasty: a comparison of two designs.
AB  - There has been a resurgence in the treatment of end-stage tibiotalar arthritis
      with prosthetic replacement. This procedure has highlighted numerous
      complications including malleolar fracture. We wanted to determine the clinical
      relevance of malleolar fracture with the two most commonly used implants in the
      United States. We retrospectively compared the first 20 STAR with the first 25
      Agility total ankle arthroplasties done by two surgeons. We examined the fracture
      rate, the timing, location, and treatment of the fracture, and the outcome in
      each group. In the Agility group, five fractures occurred, all intraoperatively.
      Four involved the medial malleolus and one involved the lateral malleolus. All
      fractures were fixed as implant stability was compromised. In the STAR group,
      there were four fractures. Two lateral malleoli fractured intraoperatively and
      were fixed. Two medial malleoli fractures occurred postoperatively and were
      treated nonoperatively. There was one medial malleolar nonunion in each group.
      The incidence of malleolar fracture was 20% in each group, comparable to results
      reported in relevant literature. We highlight some of the causes of malleolar
      fracture and describe our technique of prophylactic malleolar pinning to prevent
      this complication. Malleolar fracture is clinically relevant with the Agility and
      STAR implants and should be anticipated and prevented.

PMID- 15241151
TI  - Intraoperative measurement of distraction for ligament tensioning in total ankle
      arthroplasty.

PMID- 15241152
TI  - Radiographic and biomechanical support for fibular plating of the agility total
      ankle.
AB  - Syndesmosis nonunion with the Agility total ankle system has been associated with
      adverse radiographic findings such as radiolucency and migration. We analyzed
      radiographs and biomechanical data to determine whether the addition of a fibular
      plate was associated with improved findings related to syndesmosis union compared
      with results when two syndesmosis screws alone were used. Radiographs for 40
      consecutive ankles with the Agility total ankle system with two syndesmosis
      screws were compared with radiographs for the subsequent 40 consecutive total
      ankle replacements with an added fibular plate. When all ankles were considered,
      syndesmosis nonconsolidation at 6-10 weeks was associated significantly with
      nonunion at 5-7 months. Syndesmosis nonconsolidation at 6-10 weeks in ankles with
      screws alone was significantly higher than in ankles with plates. The
      radiolucency rate at 5-7 months also was significantly higher in ankles with
      screws alone than in ankles with plates. In the biomechanical evaluation using
      full tibia and fibula sawbones, maximum compression force within the syndesmosis
      was measured using the ISCAN sensor (TekScan). The addition of the fibular plate
      allowed significantly higher compression than the use of screws alone.

PMID- 15241153
TI  - Joint contact characteristics in agility total ankle arthroplasty.
AB  - High component contact pressures in total joint prostheses can lead to particle
      wear debris and prosthesis loosening. The contact pressures in the Agility total
      ankle prosthesis have not been investigated. In the current study, a cadaveric
      model was used to evaluate contact characteristics (average contact area, contact
      pressure, and contact peak pressures) for the Agility total ankle system. Ten
      cadaveric specimens were implanted with the Agility total ankle and axially
      loaded to 700 N. The average contact pressure of the system was 5.6 MPa with mean
      peak pressures of 21.2 MPa. In a separate phase of the study, contact
      characteristics with applied loads for each of the six component sizes showed a
      significant effect of component size on contact characteristics. When physiologic
      ankle forces are considered for normal patient activity, peak pressures observed
      in the current study may exceed recommended contact pressures (10 MPa) and the
      compressive yield point (13-22 MPa) for polyethylene. A heavy patient with a
      small ankle would not be expected to have a good outcome based on the current
      contact pressures data, whereas a heavy patient with a larger ankle might be a
      better candidate for surgery.

PMID- 15241154
TI  - Ankle arthroplasty using three generations of metal and ceramic prostheses.
AB  - Ankle arthroplasties using metal and polyethylene prostheses were done on 28
      patients (30 ankles) with painful osteoarthritis or rheumatoid arthritis between
      1975 and 1980. Significant loosening and subsidence of the metal prostheses
      occurred in most patients, and ceramic prostheses were introduced in 1980.
      Ceramic prostheses with or without cement were used to replace 60 ankles in 56
      patients with painful arthritis between 1980 and 1991. Revision surgery was
      required for five patients (five ankles) during the followup period (mean, 12
      years 6 months). Loosening and subsidence of the prostheses were seen in 50% of
      patients within 5 years after the index procedure. As a result, a new design of
      bead-formed alumina coated with hydroxyapatite was used. A tibial prosthesis
      fixed to the posterior cortex of the tibia with a screw was used from 1991. These
      new ceramic prostheses were used to replace 70 ankles in 62 patients between 1991
      and 2000. Thirty-six patients (36 ankles) with a mean age of 71 years (range, 50
      87 years) had osteoarthritis, and 26 patients (31 ankles) with a mean age of 60
      years (range, 41-76 years) had rheumatoid arthritis. During followup, with an
      average of 5 years 2 months, three patients (three ankles) required revision
      surgery (one for infection, two for talar necrosis). Overall results for patients
      with osteoarthritis were excellent in 21 ankles, good in 10 ankles, fair in two,
      ankles and poor in zero ankles. Results in patients with rheumatoid arthritis
      were excellent in five ankles, good in 16 ankles, fair in three ankles, and poor
      in two. In the intermediate study, 29 patients (31 ankles; 91.2%) with
      osteoarthritis and 19 patients (21 ankles; 76.9%) with rheumatoid arthritis were
      satisfied with the short-time results of arthroplasty.

PMID- 15241155
TI  - The effect of agility ankle prosthesis misalignment on the peri-ankle ligaments.
AB  - In the Agility total ankle replacement system, motion is constrained by the
      implant's articulating surfaces and the peri-ankle ligaments. The effects of
      plausibly occurring implant malpositioning on peri-ankle ligament functional
      extension during walking were explored in this study. The intent was to determine
      whether certain ligaments could serve as guides to assist in proper component
      positioning at implantation. Using a cadaver preparation with simulated
      physiologic motion and loading, we monitored change of ligament length of the
      anterior talofibular, posterior talofibular, calcaneofibular, and tibiocalcaneal
      ligaments resulting from controlled malpositioning of the tibial component
      relative to a neutral position. During a simulated walking cycle, effects of
      mediolateral and anterior/posterior translation, internal and external rotation,
      inversion and eversion, and elevation of the component were evaluated. In all
      cases, tibial component displacement from the neutral position caused atypical
      length change in one or more of the peri-ankle ligaments. In particular,
      anterior/posterior displacement significantly changed the lengthening behavior of
      all four tested ligaments. The anterior talofibular ligament was sensitive to
      transverse plane displacements, whereas the tibiocalcaneal ligament was sensitive
      to coronal plane displacements. For the Agility prosthesis, these two ligaments
      seem to be sensitive guides for tibial component positioning at implantation.

PMID- 15241156
TI  - Treatment of traumatic radial clubhand deformity with bone loss using the
      Ilizarov apparatus.
AB  - Radial clubhand deformity secondary to atrophic nonunion of an open distal radius
      fracture with bone loss is a challenging reconstructive problem. Two patients
      with this deformity had staged reconstruction using the Ilizarov apparatus. After
      gradual realignment of the distal radius metaphyseal fragment, a proximal to
      distal bone transport of the radial shaft was done. At completion of the bone
      transport, the docking site was augmented with autologous iliac crest bone graft.
      Both patients achieved radiographic union at the proximal and distal ends of the
      bone transport site and were satisfied with the outcome. At 3 years followup,
      full finger and elbow mobility were maintained. The wrist had improved appearance
      with limited painless mobility. Posttraumatic radial club hand deformities with
      associated bone loss can be treated successfully with staged reconstruction using
      the Ilizarov apparatus and methodology.

PMID- 15241157
TI  - Increased intraarticular pressure reduces blood flow to the femoral head.
AB  - Hemarthrosis leading to increased intracapsular pressure after an undisplaced
      femoral neck fracture is suspected to impair blood flow to the femoral head and
      may lead to osteonecrosis. We hypothesized that an increase of intraarticular
      pressure would reversibly decrease the blood flow to the femoral head. Eleven
      patients having surgical dislocations for treatment of femoroacetabular
      impingement were included in this study. Saline was injected into the intact
      intracapsular space while the blood flow to the femoral head was recorded using
      laser Doppler flowmetry. Injection of saline resulted in an increase in the
      intracapsular pressure. The injected volume of normal saline until disappearance
      of the pulsatile signal was on average 20 mL (range, 10-35 mL) with an average
      intraarticular pressure of 58 mm Hg (range, 25-88 mm Hg). Aspiration of the joint
      resulted in a return of the pulsatile flow. Hemarthrosis after undisplaced
      intracapsular fractures of the femoral neck are likely to cause an increase in
      intracapsular pressure. Decompression of the hematoma to reduce the intracapsular
      pressure is strongly advocated to optimize blood flow to the femoral head in
      acute fractures.

PMID- 15241158
TI  - The effect of adjuvant calcium phosphate coating on a porous-coated femoral stem.
AB  - A prospective, randomized, double-blind, multicenter trial was done to determine
      if the addition of hydroxyapatite and tricalcium phosphate to the porous coating
      of a cementless femoral component would result in improved clinical and
      radiographic outcomes. Patients were randomized to receive identical porous
      coated stems with (n = 159 hips) or without (n = 159 hips) hydroxyapatite and
      tricalcium phosphate coating. At 2 to 5 years followup (mean, 37 months), no
      implants were revised for aseptic loosening. There was no difference in clinical
      function between the two groups with respect to the Harris hip score or Western
      Ontario and McMaster Universities Osteoarthritis Index scores. Bony ingrowth
      occurred frequently in both groups with 99% of the hydroxyapatite and tricalcium
      phosphate group and 98% of the control group showing radiographic evidence of
      osseointegration. Implants coated with hydroxyapatite and tricalcium phosphate
      had significantly fewer radiolucencies adjacent to the porous coating, indicative
      of improved osseointegration. Radiolucencies were present in Gruen Zones 1, 7, 8,
      or 14 in 25% of the control group and in 7% of the hydroxyapatite and tricalcium
      phosphate group. This improved osseointegration could serve as an added barrier
      to particulate debris migration and increase the long-term survivorship of the
      implant.

PMID- 15241159
TI  - Comparison between bipolar hemiarthroplasty and THA for osteonecrosis of the
      femoral head.
AB  - It is controversial whether bipolar hemiarthroplasty or total hip arthroplasty
      should be done for Ficat Stage III osteonecrosis of the femoral head. A
      prospective comparative study was done using the same cementless femoral
      components for both procedures. Forty cementless bipolar hemiarthroplasties and
      31 cementless total hip arthroplasties were done in 54 patients with Ficat Stage
      III osteonecrosis of the femoral head. Age, gender, and followup were matched
      between patients having bipolar hemiarthroplasty and total hip arthroplasty.
      Treatment with total hip arthroplasty increased the total hip score more than
      treatment with bipolar hemiarthroplasty. The final pain score especially showed a
      significant difference between patients who had a bipolar hemiarthroplasty (5.5)
      and patients who had a total hip arthroplasty (5.9). Thigh pain occurred in four
      patients (four hips) from the bipolar hemiarthroplasty group and in six patients
      (six hips) from the total hip arthroplasty group. In the bipolar hemiarthroplasty
      group, gluteal pain occurred in six patients (six hips, 15%) and groin pain
      occurred in eight patients (eight hips, 20%). Dislocation occurred in two hips
      (two patients) in each group. The outer head migrated superiorly in nine hips
      (nine patients) (23%) from the bipolar hemiarthroplasty group. Because of the
      incidence of gluteal and groin pain and migration, total hip arthroplasty is a
      better procedure than bipolar hemiarthroplasty for patients with Ficat Stage III
      osteonecrosis of the femoral head.

PMID- 15241160
TI  - Distraction osteogenesis for knee arthrodesis in infected tumor prostheses.
AB  - Three patients had distraction osteogenesis as a salvage method for infected
      endoprostheses. At the first operation, the infected prosthesis was removed and
      stabilization was achieved with an external fixator to preserve limb length. An
      additional external fixator was applied later for distraction osteogenesis after
      ensuring that there was no infection. Osteotomy was done at two sites on the
      femur, or tibia and femur, respectively, as a second operation. A third surgery
      was done at the docking site at the edge of the transported bone fragments.
      Curettage, refreshing, and soft tissue release were done to enhance bone union.
      The healing index was 18.3 days/cm in Patient 1, 17.7 days/cm in Patient 2, and
      33.0 days/cm in Patient 3. All patients walk without a cane. It has been shown
      that patients can obtain a long-lasting and weight-bearable leg with our method,
      because their viable bone establishes biomechanical stability. Loss of knee
      function, a longer treatment period, and pin site treatment are the weaknesses of
      our method. Our method is indicated for patients in whom systemic disease can be
      controlled well and who have longer life expectancy.

PMID- 15241161
TI  - Dynamic confirmation of fixation techniques of the tibial tubercle osteotomy.
AB  - The tibial tubercle osteotomy is gaining popularity for revision total knee
      arthroplasty; however, the potential for tubercle displacement has been a
      concern. This study compared the mechanical behavior of the tibial tubercle
      osteotomy after screw and cerclage wire fixation. Tibial tubercle osteotomy was
      done on 40 tibias from cadavers with equal numbers fixed by either screws or
      wires. Specimens were loaded cyclically to simulate straight leg raises and then
      loaded to failure with the patellar tendon oriented 0 degrees or 25 degrees from
      the tibial axis. Tibial tubercle osteotomy cyclic displacement was greater for
      wire constructs at 25 degrees than all other constructs. Failure loads were
      greater for screw constructs at 25 degrees than both wire constructs. Screw
      constructs failed at 1429 +/- 348 N (0 degrees) and at 1925 +/- 982 N (25
      degrees). Wire constructs failed at 1072 +/- 260 N (0 degrees) and at 893 +/- 293
      N (25 degrees). Bone mineral density correlated positively with failure loads.
      Straight leg raise (400 N) and knee extension (250 N) against gravity during
      rehabilitation should be feasible with either screw or wire fixation after tibial
      tubercle osteotomy. Special care should be taken for the large patient and
      patients with decreased bone density.

PMID- 15241162
TI  - Bilateral achilles tendon ruptures in a patient with ochronosis: a case report.
AB  - We report the case of a 67-year-old man with ochronosis who had bilateral
      Achilles tendon ruptures. We reconstructed the Achilles tendon using pull-out
      wiring for the right side and an anchoring system for the left side, and
      reinforced the repair site using the peroneus brevis tendon for both sides. He
      could walk without a cane at 3 months postoperatively. Tendon ruptures in
      patients with ochronosis should be treated as pathologic ruptures because
      histologic examination reveals that both ends of the ruptured tendon and the
      insertion site at the calcaneus have extensive black pigment depositions where
      homogentisic acid and its metabolites have accumulated, and there are no normal
      collagen bundles present. Even if an Achilles tendon rupture is clinically
      diagnosed as an acute injury, the ruptured Achilles tendon should be primarily
      repaired and reinforced with autologous tissue because there are a few viable
      cells at the ruptured site, and because the tendon ruptures mainly at the
      insertion site of the calcaneus. Although this is a preliminary report, the short
      term result is good and the reconstructed sites have showed no rerupture.

PMID- 15241163
TI  - Klippel-Feil syndrome: clinical features and current understanding of etiology.
AB  - Klippel-Feil syndrome occurs in a heterogeneous group of patients unified only by
      the presence of a congenital defect in the formation or segmentation of the
      cervical spine. Numerous associated abnormalities of other organ systems may be
      present. This heterogeneity requires comprehensive evaluation of all patients and
      treatment regimes that can vary from modification of activities to extensive
      spinal surgeries. This also has made delineation of diagnostic and prognostic
      classes difficult and has complicated elucidation of the genetic etiology of the
      syndrome. Furthermore, it is unclear whether Klippel-Feil syndrome is a discrete
      entity, or if it is one point on a spectrum of congenital spinal deformities.
      Pedigree analysis has identified a human genetic locus for the disease. Mouse
      models suggest members of the PAX gene family and Notch signaling pathway as
      possible etiologic candidates. Only by identifying the link between the genetic
      etiology and the phenotypic pathoanatomy of Klippel-Feil syndrome will we be able
      to rationalize the heterogeneity of the syndrome.

PMID- 15241164
TI  - Phalangeal microgeodic syndrome resulting in rapid digital shortening.
AB  - Microgeodic phalangeal syndrome is a rare condition affecting the fingers in
      children. Radiographically, the affected phalanges show sclerosis with multiple
      small areas of osteolysis. The pathogenesis of microgeodic phalangeal syndrome is
      considered to be a transient disturbance of the peripheral circulation caused by
      cold temperatures. In most cases, the symptoms and the radiographic changes
      return to normal within several months without any treatment. We present a rare
      case of microgeodic phalangeal syndrome in the middle phalanx of the right index
      finger in an 8-year-old girl, in whom the affected phalanx shortened within 6
      weeks of the initial presentation. It was speculated that minor trauma to the
      finger might have contributed to the collapse and shortening of the phalanx. The
      current case indicates that the use of a splint for the affected finger in the
      early period after onset of symptoms might be recommended to avoid digital
      shortening.

PMID- 15241165
TI  - Smart intramedullary rod for correction of pediatric bone deformity: a
      preliminary study.
AB  - We were interested in determining if a smart intramedullary rod made of nitinol
      shape-memory alloy is capable of correcting deformed immature long bones. Because
      of limitations in our study design the process was reversed in that we examined
      the smart rod's ability to create a deformity rather than to correct one. Smart
      rods of different lengths and diameters were heat-treated to resume a radius of
      curvature of 30 to 110 mm. The low and high temperature phases of the smart rods
      were set, respectively, at 0 degrees C to 4 degrees C and 36 degrees C to 38
      degrees C. The preshaped smart intramedullary rods were implanted in the cooled
      martensite phase in the medullary canal of the tibia in eight rabbits, where they
      restored their austenite form, causing a continuous bending force. On a weekly
      basis anteroposterior and lateral radiographs of the surgically treated tibia and
      the contralateral tibia were obtained for comparison. Rabbits were euthanized 6
      weeks after surgery and computed tomography scans of both tibias were used for
      image analysis. Smart rods with a larger radius of curvature showed only minimal
      signs of remodeling; however, rods with a radius of curvature of 50 and 70 mm
      generated enough force history to create bone remodeling and deformation. The
      amount of bone deformation was highly magnified when unicortical corticotomy on
      the tension side was done. Based on this preliminary study the technology of the
      smart intramedullary rod may provide a valuable alternative method to correct
      pediatric skeletal deformities.

PMID- 15241166
TI  - Clinical relevance of calcaneal bone cysts: a study of 50 cysts in 47 patients.
AB  - The clinical relevance and nature of calcaneal cysts is controversial. The risk
      of pathologic fracture is undefined and diagnostic criteria to differentiate
      between cysts in patients who can be treated nonoperatively and patients who
      require surgical intervention are not available. To address these questions, 50
      calcaneal bone cysts in 47 patients were evaluated. The majority of cysts (40 of
      50) were asymptomatic and were treated nonoperatively. Cysts reaching a critical
      size, defined as 100% intracalcaneal cross section in the coronary plane and at
      least 30% in the sagittal plane, are at risk for becoming symptomatic and at risk
      for fracture. Fracture is a significant complication and occurred in four of 47
      patients, three of whom were treated by open reduction internal fixation and bone
      grafting. In addition, six patients with symptomatic critical size cysts without
      apparent fracture were treated by curettage and subsequent autogenous bone
      grafting or calcium-phosphate cement filling, and there were no recurrences. We
      report one of the largest series of cysts in the calcaneus. The results suggest
      that calcaneal cysts are clinically relevant because of the potential risk of
      fracture and that size is a significant factor in terms of the treatment of the
      cyst.

PMID- 15241167
TI  - Chondrosarcoma of the hand: is a wide surgical resection necessary?
AB  - Chondrosarcomas of the hand are rare and generally treated with surgical
      resection. Thirteen patients with Grade 1 chondrosarcoma of the small bones of
      the hand were followed up for a mean of 99.8 months (range, 26-293 months). In
      eight patients (Group 1) curettage and reconstruction with cancellous bone was
      done and in five patients (Group 2) a wide resection was done. No patient
      experienced relapse in Group 2. In Group 1 one patient had a local relapse 18
      months after intralesional resection. Using the Musculoskeletal Tumor Society
      score for evaluation, the clinical results showed an average of 98% and 95% of
      the normal function in Groups 1 and 2, respectively. None of the patients had
      evidence of systemic spread of the disease. With a relapse rate of 12.5% and no
      distant metastases after curettage, intralesional resection is the preferred
      method of treatment in Grade 1 chondrosarcoma of the hand, allowing the patient
      to avoid amputation and major loss of function.

PMID- 15241168
TI  - Possible metastasis of osteosarcoma to a remote biopsy site: a case report.
AB  - In a patient who presented with an osteosarcoma of the proximal humerus, systemic
      staging revealed a lesion in the contralateral humerus, which was shown to be an
      enchondroma after open biopsy. The patient had a local recurrence develop, which
      necessitated forequarter amputation. Shortly thereafter, the patient had pain
      develop at the contralateral biopsy site, and examinations and repeat biopsy
      revealed metastatic osteosarcoma. We think it is likely that surgical trauma
      contributed to the development of this unusual metastasis. In this clinical
      situation, consideration should be given to doing the biopsy and definitive
      resection on separate occasions.

PMID- 15241169
TI  - Results of giant cell tumor of bone treated with intralesional excision.
AB  - Treatment of giant cell tumor of bone ranges from intralesional curettage to en
      bloc resection. We think that intralesional treatment can be done with low
      recurrence and complication rates and that these patients have good functional
      results. The results for 40 patients treated by one surgeon with one technique
      for giant cell tumor of bone between 1985-1999 were reviewed. All patients were
      treated with intralesional excision of the tumor with adjunctive cautery, phenol,
      and methylmethacrylate. All patients had been followed up for a minimum of 2
      years with the mean followup of 76 months (range, 26-178 months). In addition,
      recent functional evaluations were done on 23 patients at a mean followup of 90
      months (range, 28-175 months). The local recurrence rate was 12.5%. The
      nononcologic complication rate was 7.5%. Using the Musculoskeletal Tumor Society
      functional evaluation, 93% of the patients had excellent results. This long-term
      followup study on patients treated with intralesional excision and methacrylate
      showed a low recurrence rate similar to those cited in the literature.
      Additionally, the complication rate was low and the function results were
      excellent.

PMID- 15241170
TI  - Nonunion of the humeral shaft: long lateral butterfly fracture--a nonunion
      predictive pattern?
AB  - Retrospective review of 30 patients with nonunion of the humeral shaft treated
      from 1984-1999 revealed nine patients with an initial fracture pattern which to
      our knowledge was not described previously. Humeral fractures originated at the
      junction of the proximal and middle thirds of the diaphysis as an hemitransverse
      medial fracture that extended with a great lateral butterfly third fragment with
      its distal portion long and sharp. The patients were women approximately 60 years
      old. Eight fractures progressed to nonunion after initial conservative treatment.
      All fractures followed the same pattern: the proximal humeral fragment healed
      with the proximal portion of the third fragment, but an atrophic nonunion between
      the proximal humeral fragment, the distal humeral fragment, and the distal
      portion of the third fragment developed. The treatment required a technique
      adapted to this type of nonunion consisting of retrograde flexible intramedullary
      nailing, cerclage wires, and bone grafts.

PMID- 15241171
TI  - Metabolic measurement techniques to assess bone fracture healing: a preliminary
      study.
AB  - The purpose of this study was to project the effectiveness of using positron
      emission tomography for evaluation of fracture healing using the analogous method
      of liquid scintillation. A reproducible comminuted fracture model in rabbit
      femurs was stabilized with external fixation. Thirty-nine rabbits were divided
      into four groups: Group A had slight distraction, Group B had shortening, Group C
      had a bone defect, and Group D was the sham control group. At 2 and 4 weeks after
      fracture, the femurs had liquid scintillation measurements using 2-[14C]
      deoxyglucose (2DG C-14). Glucose uptake was significantly elevated in the
      experimental limb relative to the contralateral control femurs at both times. The
      distraction group showed a significant decrease in uptake from 2-4 weeks. There
      was a high correlation between the liquid scintillation measurements and the
      radiographic fracture healing scores, with higher levels of 2DG C-14 uptake
      corresponding to lower levels of fracture healing calcification. The high
      correlation found between 2DG C-14 uptake and radiographic scores suggests that
      positron emission tomography used in conjunction with a glucose-based
      radiopharmaceutical such as 2-[18F]fluoro-2-deoxyglucose can monitor the fracture
      healing process effectively.

PMID- 15241172
TI  - The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery
      system.
AB  - Local biodegradable carriers have been studied for use as a skeletal drug
      delivery system. This study investigated the efficacy of a local biodegradable
      composite composed of hydroxyapatite, plaster of Paris, and chitosan impregnated
      with antibiotics to treat methicillin-resistant Staphylococcus aureus. The
      composite, impregnated with vancomycin, fosfomycin, or sodium fusidate was tested
      for its sustained elution characteristics during 3 months and compared with
      similarly impregnated polymethylmethacrylate using the modified disc diffusion
      technique. Physicochemical properties using scanning electron microscopy and xray
      diffraction analysis of each preparation also were analyzed. Vancomycin and
      fosfomycin incorporated into the hydroxyapatite composite inhibited the organism
      for 3 months, whereas sodium fusidate was effective only for 3 weeks. Vancomycin
      and fosfomycin loaded into the hydroxyapatite composite had a significantly
      better inhibitive effect than when loaded in polymethylmethacrylate, whereas
      sodium fusidate loaded in polymethylmethacrylate showed a significantly better
      inhibitive effect than when loaded in the hydroxyapatite composite. Scanning
      electron microscopy and xray diffraction analysis elucidated the patterns of each
      drug release profile. The local hydroxyapatite composite is a promising local
      biodegradable delivery system for vancomycin and fosfomycin, whereas PMMA is a
      better carrier for sodium fusidate in treating methicillin-resistant
      staphylococcus aureus osteomyelitis.

PMID- 15241173
TI  - Microspheres accurately predict regional bone blood flow.
AB  - Even though the microsphere method frequently is used to determinate bone blood
      flow, validation of this technique for bone blood flow measurement is incomplete.
      The method is based on the principle that injected microspheres are distributed
      with the arterial blood and trapped in the capillaries because of their diameter
      (15 microm). The number of spheres lodged in an organ is proportional to its
      blood flow. The number of radioactive or fluorescent microspheres in a specific
      organ is determined indirectly by measuring radioactivity or fluorescence
      intensity in the organ. In this study the reliability and precision of the
      microsphere method for determining bone blood flow was established using
      radioactive and fluorescent microspheres. Six female, anesthetized New Zealand
      rabbits received left ventricular injections of pairs of fluorescent and/or
      radioactive microspheres. The humerus, femur, and tibia were dissected in a
      standardized manner and blood flow was determined in each sample. Comparison of
      relative blood flow values showed an excellent correlation between radioactive
      and fluorescent microspheres. The percentage difference and variation between two
      simultaneously injected sets of microspheres was minimal for radioactive
      microspheres (0.8% +/- 9.6%) and for fluorescent microspheres (0.2% +/- 11.4%).
      Regional bone blood flow in different regions of the femur, tibia, or humerus
      ranged from 2.2-28.1 mL/minute/100 g, but there was no significant difference
      between right and left bone samples of the same region after repeated
      measurement. Radioactive and fluorescent microspheres allow precise determination
      of regional bone blood flow.

PMID- 15241174
TI  - The effect of hyaluronic acid on a rabbit model of full-thickness cartilage
      repair.
AB  - The current study investigated whether hyaluronate exerts a beneficial effect on
      articular cartilage repair. Nineteen rabbits had bilateral knee arthrotomies, and
      2-mm full-thickness cartilage defects were created on each medial femoral
      condyle. Rabbits received intraarticular injections (0.5 mL) of hyaluronic acid
      once a week for 3 weeks in the right knee, started at either 1 or 3 weeks after
      injury. The left knees, which served as controls, were injected with 0.5 mL
      normal saline. Cohorts of each group were euthanized at 2 and 6 months, and
      histologic sections of the injury sites were evaluated for repair tissue. No
      significant differences were seen in the quantity or quality of the repair tissue
      at either 2 or 6 months. Hyaluronate and saline-treated defects showed persistent
      fibrillation, poor matrix staining, and incomplete void filling, irrespective of
      the injection timing. Hyaluronate did not provide protection to zones peripheral
      to the injury site, and did not significantly alter the healing process in this
      model of acute full-thickness cartilage injuries.

PMID- 15241175
TI  - Ulnar mass in a 51-year-old woman.

PMID- 15241176
TI  - Forearm mass in a 31-year-old man.

PMID- 15241177
TI  - Hip pain in a 38-year-old man.

PMID- 15241178
TI  - Osteochondritis dissecans of the knee: long-term results of excision of the
      fragment.
AB  - Optimal treatment of osteochondritis dissecans of the knee has been
      controversial. Various treatment methods have resulted in good short-term
      results. Unfortunately, the age range of the patients who typically require
      treatment of this disorder is young enough that long-term results become
      critical. We did a retrospective review to evaluate our hypothesis that simple
      excision of a loose osteochondritis dissecans fragment results in a higher
      percentage of unacceptable outcomes when compared with treatment methods that
      preserve the articular cartilage. Between 1982 and 1993, 30 knees in 29 patients
      had arthroscopic or arthroscopically assisted surgical excision of a symptomatic
      loose osteochondritis dissecans lesion of the knee. Seventeen patients who had
      excision were available for followup. There were 12 males and five females. The
      average age of the patients at the time of surgery was 26 years (range, 12.5-38
      years). The average length of followup was 8.9 years (range, 4-15 years). Results
      were graded using the Hughston rating scale for osteochondritis dissecans. Only
      six of 17 patients (35%) had a good or excellent result. Eleven of 17 (65%) had a
      fair or poor result. We think our results at intermediate followup support our
      hypothesis, and we recommend aggressive attempts to preserve the articular
      cartilage and avoid excision of the fragments when possible.

PMID- 15241179
TI  - Impaired neurovascular coupling by transhemispheric diaschisis in rat cerebral
      cortex.
AB  - In acute brain disorders, elimination of the excitatory output from an injured
      brain region reduces activity in connecting brain regions remote from the lesion
      site (i.e., diaschisis). The authors examined the effect of functional ablation
      of the left cerebral cortex by cortical spreading depression (CSD) or topical
      application of tetrodotoxin on single cell spiking activity, baseline CBF, and
      neurovascular coupling in the right rat sensory cortex. CSD or tetrodotoxin in
      left cortex reduced the right cortical spontaneous spike rate by 36% and 45%,
      respectively. Baseline CBF in the right cortex was unaffected by a left-sided
      CSD, but decreased by 12% for left cortical application of tetrodotoxin. This
      suggested dissociation between spontaneous spiking activity and basal CBF. Left
      in-fraorbital nerve stimulation evoked local field potentials in right cerebral
      cortex that were reduced in amplitude by 19% for left CSD and by 23% for left
      tetrodotoxin application. The corresponding declines in the evoked CBF responses
      were 42% for CSD and 23% for tetrodotoxin. Vascular reactivity to adenosine
      remained unchanged in right cortex. Thus, transhemispheric diaschisis produced a
      pronounced decrease in the spontaneous spike rate accompanied by no reduction or
      a small reduction in basal CBF, and an attenuation in amplitudes of evoked
      synaptic responses and corresponding rises in CBF. The findings suggest that
      disturbed neurovascular coupling may contribute to the disturbance in brain
      function in acute transhemispheric diaschisis.

PMID- 15241180
TI  - Induction of caspase-mediated cell death by matrix metalloproteinases in cerebral
      endothelial cells after hypoxia-reoxygenation.
AB  - Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of
      cerebral ischemia by degrading matrix components in the neurovascular unit. In
      this study, the authors document a pathway by which MMPs interfere with cell
      matrix interactions and trigger caspase-mediated cytotoxicity in brain
      endothelial cells. Hypoxia-reoxygenation induced endothelial cytotoxicity.
      Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase
      mediated. The temporal profile of caspase-3 activation was matched by elevations
      in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation
      and reduced endothelial cell death. Degradation of matrix fibronectin confirmed
      the presence of extracellular proteolysis. Increasing integrin-linked kinase
      signaling with the beta1 integrin-activating antibody (8A2) ameliorated
      endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to
      caspase-mediated brain endothelial cell death after hypoxia-reoxygenation by
      disrupting cell-matrix interactions and homeostatic integrin signaling.

PMID- 15241182
TI  - Laser speckle flowmetry for the study of cerebrovascular physiology in normal and
      ischemic mouse cortex.
AB  - Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional
      cerebral blood flow (CBF) with high temporal and spatial resolution. The authors
      show that LSF can image the spatiotemporal dynamics of CBF changes in mice
      through an intact skull. When measured by LSF, peak CBF increases during whisker
      stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF)
      measurements, and were greater within the branches of the middle cerebral artery
      supplying barrel cortex than within barrel cortex capillary bed itself. When LSF
      was used to study the response to inhaled CO2 (5%), the flow increase was similar
      to the response reported using LDF. For the upper and lower limits of
      autoregulation, mean arterial pressure values were 110 and 40 mm Hg,
      respectively. They also show a linear relationship between absolute resting CBF,
      as determined by [C]iodoamphetamine technique, and 1/tau(c) values obtained using
      LSF, and used 1/tau(c) values to compare resting CBF between different animals.
      Finally, the authors studied CBF changes after distal middle cerebral artery
      ligation, and developed a model to investigate the spatial distribution and
      hemodynamics of moderate to severely ischemic cortex. In summary, LSF has
      distinct advantages over LDF for CBF monitoring because of high spatial
      resolution.

PMID- 15241181
TI  - The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress
      through protein kinase B coupled to FOXO3a and mitochondrial membrane potential.
AB  - Nicotinamide, a beta-nicotinamide adenine dinucleotide (NAD) precursor and an
      essential nutrient for cell growth and function, may offer critical insights into
      the specific cellular mechanisms that determine neuronal survival, since this
      agent significantly impacts upon both neuronal and vascular integrity in the
      central nervous system. The authors show that nicotinamide provides broad, but
      concentration-specific, protection against apoptotic genomic DNA fragmentation
      and membrane phosphatidylserine exposure during oxidative stress to secure
      cellular integrity and prevent phagocytic cellular demise. Activation of the
      protein kinase B (Akt1) pathway is a necessary requirement for nicotinamide
      protection, because transfection of primary hippocampal neurons with a plasmid
      encoding a kinase-deficient dominant-negative Akt1 as well as pharmacologic
      inhibition of phosphatidylinositol-3-kinase phosphorylation of Akt1 eliminates
      cytoprotection by nicotinamide. Nicotinamide fosters neuronal survival through a
      series of intimately associated pathways. At one level, nicotinamide directly
      modulates mitochondrial membrane potential and pore formation to prevent
      cytochrome c release and caspase-3-and 9-like activities through mechanisms that
      are independent of the apoptotic protease activating factor-1. At a second level,
      nicotinamide maintains an inhibitory phosphorylation of the forkhead
      transcription factor FOXO3a at the regulatory sites of Thr and Ser and governs a
      unique regulatory loop that prevents the degradation of phosphorylated FOXO3a by
      caspase-3. Their work elucidates some of the unique neuro-protective pathways
      used by the essential cellular nutrient nicotinamide that may direct future
      therapeutic approaches for neurodegenerative disorders.

PMID- 15241183
TI  - Brain function early after stroke in relation to subsequent recovery.
AB  - This study aimed to characterize brain activation and perfusion early after
      stroke within cortical regions that would later change activation during
      recovery. Patients were studied serially after stroke (mean t1, = 16 days after
      stroke, t2 = 3.5 months later) using perfusion-weighted imaging and functional
      magnetic resonance imaging during finger movement. Controls (n = 7) showed no
      significant change in regional activation volumes over time. Among stroke
      patients (n = 8), however, recovery was accompanied by several patterns of
      functional magnetic resonance imaging change, with increased activation volumes
      over time in five patients and decreased in two. Most regions increasing
      activation over time were in the stroke hemisphere. Of the five patients showing
      increased activation over time, specific activation foci enlarged at t2 were
      already activated at t1 in four patients, and at least one focus growing from t1
      to t2 was in a different arterial distribution from the infarct in all five
      patients. Perfusion of sensorimotor cortex at t1 was generally not reduced in the
      stroke hemisphere (94% of noninfarcted hemisphere). Improved clinical outcome was
      related to increased activation within sensory cortices of both brain sides,
      including bilateral secondary somatosensory areas. Early after stroke, cortical
      activation that will later increase in parallel with recovery is often already
      identifiable, can be remote from the vascular territory of the infarct, and is
      not likely hindered by reduced perfusion. The findings may be useful for
      restorative interventions introduced during the weeks after a stroke.

PMID- 15241184
TI  - Sustained poststimulus elevation in cerebral oxygen utilization after vascular
      recovery.
AB  - The brain's response to functional activation is characterized by focal increases
      in cerebral blood flow. It is generally assumed that this hyperemia is a direct
      response to the energy demands of activation, the so-called flow-metabolism
      coupling. Here we report experimental evidence that increases in oxygen
      metabolism can occur after activation without increases in flow. When using
      multimodality functional MRI (fMRI) to study visual activation in human brain, we
      observed a postactivation period of about 30 seconds during which oxygen
      consumption remained elevated, while blood flow and volume had already returned
      to baseline levels. The finding of such a prolonged and complete dissociation of
      vascular response and energy metabolism during the poststimulus period indicates
      that increased metabolic demand needs not per se cause a concomitant increase in
      blood flow. The results also show that the postactivation undershoot after the
      positive blood-oxygen-level-dependent hemodynamic response in fMRI should be
      reinterpreted as a continued elevation of oxygen metabolism, rather than a
      delayed blood volume compliance.

PMID- 15241185
TI  - Adenosine A(1) receptor antagonist and mitochondrial ATP-sensitive potassium
      channel blocker attenuate the tolerance to focal cerebral ischemia in rats.
AB  - Involvement of adenosine and adenosine triphosphate-sensitive potassium (KATP)
      channels in the development of ischemic tolerance has been suggested in global
      ischemia, but has not been studied extensively in focal cerebral ischemia. This
      study evaluated modulating effects of adenosine A1 receptor antagonist DPCPX (8
      cyclopentyl-1,3-dipropylxanthine) and mitochondrial KATP channel blocker 5HD (5
      hydroxydecanoate) on the development of tolerance to focal cerebral ischemia in
      rats. Preconditioning with 30-minute middle cerebral artery occlusion (MCAO)
      reduced cortical and subcortical infarct volume following 120-minute MCAO (test
      ischemia) given 72 hours later. The neuroprotective effect of preconditioning was
      attenuated by 0.1 mg/kg DPCPX given before conditioning ischemia (30-minute
      MCAO), but no influence was provoked when it was administered before test
      ischemia. DPCPX had no effect on infarct volume after conditioning or test
      ischemia when given alone. The preconditioning-induced neuroprotection
      disappeared when 30 mg/kg 5HD was administered before test ischemia. These
      results suggest a possible involvement of adenosine A1 receptors during
      conditioning ischemia and of mitochondrial KATP channels during subsequent severe
      ischemia in the development of tolerance to focal cerebral ischemia.

PMID- 15241186
TI  - Quantitative rt-PCR analysis of uncoupling protein isoforms in mouse brain
      cortex: methodological optimization and comparison of expression with brown
      adipose tissue and skeletal muscle.
AB  - Uncoupling proteins (UCPs) present in the inner mitochondrial membrane are
      involved in uncoupling respiration from ATP synthesis. Five UCP isoforms have
      been identified but information about their presence and level of expression in
      the central nervous system remains incomplete. To determine the nature and
      proportion of UCP isoform mRNAs present in brain cortex, we developed and
      optimized a specific quantitative reverse-transcription polymerase chain reaction
      procedure. Optimal range of RNA concentrations to be used in the reverse
      transcriptase reaction was determined. Primer design and concentration were
      optimized for each target gene while polymerase chain reaction efficiency was
      assessed for a range of reverse-transcriptase dilutions. Genomic contribution to
      the quantitative signal was evaluated for each isoform and minimized. Three
      reference genes were tested for normalization, and beta-actin was found to be the
      most stable among tissues. Results indicate that brain cortex contains
      significant amounts of all UCP mRNAs, with UCP5 and UCP4 being the most abundant,
      as opposed to brown adipose tissue and skeletal muscle, which predominantly
      express UCP1 and UCP3, respectively. These data provide a first quantitative
      assessment of UCP mRNA expression in mouse brain, showing the presence of all
      five isoforms with distinct proportions, thus suggesting specific roles in the
      central nervous system.

PMID- 15241187
TI  - Characterization of a novel chronic photothrombotic ring stroke model in rats by
      magnetic resonance imaging, biochemical imaging, and histology.
AB  - A novel photothrombotic ring stroke model was characterized by multiparametric
      magnetic resonance imaging, imaging of cerebral blood flow (CBF), adenosine
      triphosphate (ATP), pH, and histology. Ischemia was initiated by transosseous
      irradiation of a predefined brain area intravenously perfused by the
      photosensitive dye erythrosin B in male Wistar rats. In the region of the primary
      ring-lesion, the phototoxic reaction caused necrosis reflected by low relative
      ATP levels (28 +/- 15%), alkalosis (pH: 7.35 +/- 0.50), and histologic evidence
      at 14 days after lesion induction. In the ring-encircled interior region (region
      at-risk), spontaneous tissue reperfusion (relative CBF: 93 +/- 3%) enabled
      partial tissue preservation. This was demonstrated by a less impaired energy
      metabolism (ATP: 65 +/- 23%), normal pH (7.01 +/- 0.50), and still normal
      cellular structures shown by histologic staining. Analysis of the temporal
      characteristics within the region-at-risk revealed a slow continuous increase of
      the apparent diffusion coefficient of water (ADC) to 144 +/- 16% of control (14d)
      and an early vasogenic edema, reflected by an increase of the T2 relaxation time
      to 143 +/- 17% of control (2d). Both final ADC and T2 correlated well with the
      tissue pH within the region-at-risk, thus emphasizing the usefulness of this
      multiparametric noninvasive imaging approach.

PMID- 15241188
TI  - The effect of indomethacin on intracranial pressure, cerebral perfusion and
      extracellular lactate and glutamate concentrations in patients with fulminant
      hepatic failure.
AB  - Uncontrolled increase in intracranial pressure (ICP) continues to be one of the
      most significant causes of early death in patients with acute liver failure
      (ALF). In this study, we aimed to determine the effects of indomethacin on ICP
      and cerebral perfusion pressure in twelve patients with ALF and brain edema (9
      females/3 males, median age 49,5 (range 21 to 64) yrs.). Also changes in cerebral
      perfusion determined by transcranial Doppler technique (Vmean) and jugular bulb
      oxygen saturation (SvjO2) were measured, as well as brain content of lactate and
      glutamate by microdialysis technique. Finally, we determined the cerebral blood
      flow autoregulation before and after indomethacin injection. We found that
      indomethacin reduced ICP from 30 (7 to 53) to 12 (4 to 33) mmHg (P < 0.05). The
      cerebral perfusion pressure increased from 48 (0 to 119) to 65 (42 to 129) mmHg
      (P < 0.05), while Vmean and SvjO2 on average remained unchanged at 68 (34 to 126)
      cm/s and 67 (28 to 82) %, respectively. The lactate and glutamate in the brain
      tissue were not altered (2.1 (1.8 to 7.8) mmol/l and 34 (2 to 268) micromol/l,
      respectively) after injection of indomethacin. Cerebral blood flow autoregulation
      was impaired in all patients before injection of indomethacin, but was not
      restored after administration of indomethacin. We conclude that a bolus injection
      of indomethacin reduces ICP and increases cerebral perfusion pressure without
      compromising cerebral perfusion or oxidative metabolism in patients with ALF.
      This finding indicates that indomethacin may be valuable as rescue treatment of
      uncontrolled intracranial hypertension in fulminant hepatic failure.

PMID- 15241189
TI  - Progesterone enhances functional recovery after middle cerebral artery occlusion
      in male mice.
AB  - Sex differences have been observed in the outcome after ischemia that are
      believed to be attributable to sex steroid hormones. The present study
      investigated the possible benefits of progesterone administration after focal
      cerebral ischemia. Male mice underwent 60-minute middle cerebral artery occlusion
      (MCAO) and received progesterone (8 mg/kg, intraperitoneally) or vehicle
      (dimethyl sulfoxide) 1, 6, and 24 hours after MCAO. The lesion volume at 48 hours
      after MCAO was significantly reduced (P < 0.05) in progesterone-treated mice
      compared with vehicle-treated mice. All other mice underwent tests of well being
      (survival rate and body weight recovery), motor ability (grid test and rotarod),
      and cognitive ability (water maze) for up to 21 days. MCAO significantly worsened
      outcome in all of these tests compared with shams. Progesterone treatment was
      beneficial in that compared with vehicle, it significantly improved survival
      rate, weight recovery, and motor ability. This improvement was most apparent
      during water maze testing, where progesterone-treated mice were indistinguishable
      from shams in terms of acquiring the task. These results indicate beneficial
      effects of progesterone administration after cerebral ischemia and illustrate the
      need to further investigate the mechanisms of progesterone action.

PMID- 15241190
TI  - Neural stem cells in the subventricular zone are resilient to hypoxia/ischemia
      whereas progenitors are vulnerable.
AB  - Perinatal hypoxic-ischemic (H/I) brain injury remains a major cause of neurologic
      disability. Because we have previously demonstrated that this insult depletes
      cells from the subventricular zone (SVZ), the goal of the present investigation
      was to compare the relative vulnerability to H/I of neural stem cells versus
      progenitors. The dorsolateral SVZs of P6 rats were examined at 2 to 48 hours of
      recovery from H/I using hematoxylin and eosin, in situ end labeling (ISEL),
      terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate
      biotin nick end labeling (TUNEL), electron microscopy, and immunofluorescence.
      Pyknotic nuclei and ISEL cells were observed by 4 hours of recovery, peaked at 12
      hours, and persisted for at least 48 hours. Many active-caspase-3 cells were
      observed at 12 hours and they comprised one third of the total TUNEL population.
      Electron microscopy revealed that hybrid cell deaths predominated at 12 hours of
      recovery. Importantly, few dying cells were observed in the medial SVZ, where
      putative stem cells reside, and no nestin medial SVZ cells showed caspase-3
      activation. By contrast, active-caspase-3/PSA-NCAM progenitors were prominent in
      the lateral SVZ. These data demonstrate that early progenitors are vulnerable to
      H/I, whereas neural stem cells are resilient. The demise of these early
      progenitors may lead to the depletion of neuronal and late oligodendrocyte
      progenitors, contributing to cerebral dysgenesis after perinatal insults.

PMID- 15241191
TI  - The upregulation of cognate and inducible heat shock proteins in the anoxic
      turtle brain.
AB  - Because heat shock proteins (HSPs) have an important protective function against
      ischemia/anoxia in mammalian brain, the authors investigated the expression of
      Hsp72 and Hsc73 in the anoxia-surviving turtle brain. Unlike the mammalian brain,
      high levels of Hsp72 were found in the normoxic turtle brain. Hsp72 levels were
      significantly increased by 4 hours of anoxia, remained constant until 8 hours,
      and then decreased to baseline at 12 hours. By contrast, Hsc73 was progressively
      increased throughout 12 hours of anoxia. This differential expression suggests
      different protective roles: Hsp72 in the initial downregulatory transition phase,
      and Hsc73 in maintaining neural network integrity during the long-term
      hypometabolic phase.

PMID- 15241194
TI  - Integrate research into your practice.

PMID- 15241195
TI  - Diabetes ABCs: do you know them, get them, improve them?

PMID- 15241197
TI  - Using clinical guidelines in home care: for patients with diabetes.

PMID- 15241198
TI  - Disabilities, diabetes, and devices.

PMID- 15241199
TI  - Medications and resources for glycemic control.

PMID- 15241201
TI  - 7 basic principles of diabetes care.

PMID- 15241202
TI  - Nutrition tips for managing diabetes on a limited budget.

PMID- 15241203
TI  - Diabetes resources on the World Wide Web.

PMID- 15241204
TI  - Creating a diabetes education home care program: one agency's success story.

PMID- 15241205
TI  - Pediatric critical care for children with congenital neurodevelopmental
      diagnoses.

PMID- 15241206
TI  - Noninvasive ventilation in pediatrics: we still do not have a consistent base.

PMID- 15241207
TI  - Noninvasive measurement of cardiac output: the continuing saga and lessons
      learned.

PMID- 15241208
TI  - The PICU nightmare.

PMID- 15241209
TI  - Another publication on an endotracheal tube?

PMID- 15241210
TI  - Manpower shortage in pediatric cardiac intensive care: how can we undo this
      Gordian knot?

PMID- 15241211
TI  - Fighting the flu: the rise of the machine.

PMID- 15241216
TI  - Human middle ear transfer function measured by double laser interferometry
      system.
AB  - HYPOTHESIS: Simultaneous measurements of vibrations on the stapes footplate,
      incudostapedial (IS) joint, and tympanic membrane (TM) can be made in both normal
      and drained cochleae, and the stapes displacement transfer function (S-DTF) and
      TM displacement transfer function (TM-DTF) are derived. BACKGROUND: A single
      laser Doppler interferometer previously has been used for measuring movement of
      the stapes or TM in temporal bones. However, there may be a limitation to
      optimally describing acoustic-mechanical transmission when the interferometer and
      temporal bone are moved frequently during experimental recordings. Simultaneous
      measurements of vibrations of the TM and stapes footplate, or TM and IS joint may
      reveal different acoustic-mechanical characteristics of the middle ear. METHODS:
      Dual laser interferometers simultaneously measured vibrations of the TM, IS
      joint, and stapes in 10 temporal bones with both intact and drained cochleae.
      From these measurements, the middle ear transfer function was expressed as the S
      DTF, TM-DTF, and displacement transmission ratio (DTR). RESULTS: Simultaneous
      displacements of the TM, IS joint, and stapes footplate induced by sound pressure
      in the ear canal were recorded in both amplitude and phase. The middle ear
      transfer functions in terms of displacement ratio confirmed published single
      interferometer data but provided new information from drained cochlea.
      CONCLUSION: Stapes and TM displacement transfer functions were determined using
      dual interferometry, provided accurate amplitude and phase relationships from
      stapes footplate, IS joint, and TM, with new data from drained and normal
      cochlea.

PMID- 15241217
TI  - Titanium clip prosthesis.
AB  - OBJECTIVE: Prostheses for the reconstruction of a defective ossicular chain
      should be stable and firmly anchored to the ossicular remnants. This will prevent
      a defective connection from causing diminished sound transmission efficiency and
      will keep the prosthesis from tilting or even losing contact, which would result
      in a sound transmission block. Through temporal bone experimentation, we have
      consequently developed a very lightweight titanium prosthesis, which is fastened
      onto the stapes head with a clip mechanism. METHODS: When temporal bone
      experiments using laser Doppler vibrometry confirmed that the prosthesis
      functioned well acoustically and when luxation experiments proved that it could
      be safely used without the risk of stapes dislocation, the prosthesis was used in
      a clinical application within an observational study. The University of Dresden
      Otorhinolaryngological Hospital as well as seven surgeons from five other
      hospitals participated in the study. RESULTS: The results of 133 operations
      showed that, in over 90% of the cases, the prosthesis could be implemented
      without problems and with good mechanical stability. The first acoustical results
      obtained during the first year from 49 patients showed a sound transmission
      improvement range from 12 dB to 14 dB. CONCLUSION: With the clip prosthesis, it
      seems possible to further improve defective middle ear function, which would
      allow the patient to regain social hearing after middle ear reconstruction. The
      reliability of the fastening is an innovation. Revision operations showed a
      stable prosthesis-stapes complex in the middle of a recurring cholesteatoma and
      the prosthesis could always be easily pulled from the stapedial suprastructure.

PMID- 15241218
TI  - Partial promontory technique in stapedotomy cases with narrow niche.
AB  - OBJECTIVE: The objective of this study was to examine clinical and audiometric
      outcomes of a laser partial promontory technique in stapedotomy cases with a
      narrow oval window niche. STUDY DESIGN: We conducted a retrospective chart
      review. SETTING: This study was conducted at a tertiary referral center.
      PATIENTS: We studied 59 patients who underwent a partial promontory technique
      with stapedotomy between 1994 and 2000. Seventy-two patients who underwent
      primary stapedotomy without promontory technique served as a control group.
      METHODS: Preoperative and postoperative audiometric results were obtained for 59
      patients undergoing laser stapedotomy with a narrow oval window niche. The
      partial promontory removal was performed with a KTP laser. Results were compared
      with 72 primary laser stapedotomy cases without the promontory technique within
      the same time period and analyzed using paired Student t test. RESULTS: Ninety
      percent of the partial promontory cases were successful (air-bone gap [ABG] <10
      dB). The mean postoperative ABG was 5.1 dB, which was comparable to the non
      promontory cases (p = 0.7). The mean change in postoperative bone conduction was
      also comparable (p = 0.98). There were no cases of sensorineural hearing loss. An
      overhanging facial nerve was present in 32% of the narrow niche cases and a
      dehiscent facial nerve was encountered in 17% of these cases. CONCLUSIONS:
      Partial laser removal of the promontory as an adjunct to laser stapedotomy cases
      with a narrow oval window niche is a safe, effective technique with comparable
      results to primary laser stapedotomy.

PMID- 15241219
TI  - Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene:
      evidence for a shared genetic etiology with osteoporosis.
AB  - HYPOTHESIS: There is an association between otosclerosis and osteoporosis.
      BACKGROUND: Both osteoporosis and otosclerosis are common bone diseases to which
      relatively large portions of the population are genetically predisposed.
      Recently, a strong association has been described between osteoporosis and an Sp1
      binding site of putative functional significance in the first intron of the
      COL1A1 gene. METHODS: We applied polymerase chain reaction-based restriction
      enzyme analysis to determine the polymorphic distribution of the Sp1 site in 100
      patients with otosclerosis and 108 control subjects. RESULTS: This study showed a
      significant association between otosclerosis and the COL1A1 first intron Sp1
      site. The allelic frequency of the Sp1 site is very similar between otosclerosis
      and osteoporosis. CONCLUSION: Some cases of otosclerosis and osteoporosis could
      share a functionally significant polymorphism in the Sp1 transcription factor
      binding site in the first intron of the COL1A1 gene.

PMID- 15241220
TI  - Measles virus prevalence in otosclerotic stapes footplate samples.
AB  - HYPOTHESIS: The cause of otosclerosis is still unknown. Persistent measles virus
      infection of the otic capsule is supposed to be one of the etiologic factors in
      otosclerosis. Chronic viral antigen expression on the surface of infected cells
      can induce a secondary autoimmune reaction against the otic capsule. BACKGROUND:
      In the past 15 years, some reports proposed the possible etiologic role of
      measles virus in otosclerosis. The presence of measles virus was shown in
      otosclerotic patients by reverse-transcriptase polymerase chain reaction
      amplification of the viral RNA, detecting the viral proteins by
      immunohistochemistry and detecting antimeasles immunoglobulin G in the perilymph
      samples. Many concerns were elicited by these results. METHODS: Nucleic acid was
      extracted from pulverized, frozen stapes footplate samples of otosclerotic
      patients. Measles virus RNA was amplified by reverse-transcriptase polymerase
      chain reaction: reverse transcription and the first round polymerase chain
      reaction amplification was performed by heat stable recombinant Thermus
      thermophilus polymerase, whereas in the nested round, polymerase chain reaction
      Taq-polymerase was used. Measles virus nucleoprotein RNA-specific oligonucleotide
      primers were used in these reactions. An Edmonston-type measles virus served as a
      positive control and cortical bone fragments or stapes superstructures served as
      negative controls. RESULTS: Among 34 otosclerotic patients, 20 stapes footplate
      samples contained measles virus RNA. Measles virus RNA was not detected in other
      bone specimens of the patients. CONCLUSION: The etiologic role of measles virus
      in the pathogenesis of otosclerosis should be considered. The 14 negative samples
      may be genetically determined otosclerotic cases.

PMID- 15241221
TI  - Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on
      hearing level.
AB  - OBJECTIVE: To investigate the effect of changes within the spiral ligament and
      stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament
      hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear
      otosclerosis and described changes in ion transport molecule expression. STUDY
      DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-two
      cochleae from 24 temporal bone donors with histologic evidence of cochlear
      otosclerosis, including spiral ligament hyalinization. INTERVENTION: Audiography.
      MAIN OUTCOME MEASURES: Measurements of spiral ligament width, stria vascularis,
      and bone-conduction thresholds were compared by the amount of hyalinization.
      Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic
      anhydrase II were assessed by immunohistochemical techniques. RESULTS:
      Hyalinization most often involved the posterior basal turn (88%) and the
      posterior middle turn (27%). Spiral ligament hyalinization correlated
      significantly with stria vascularis atrophy in the posterior middle turn of the
      cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant
      association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction
      thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of
      stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed
      decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes
      and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the
      spiral ligament in cochlear otosclerosis sections compared with normal cochlea.
      Na,K-ATPase staining within the stria vascularis was further decreased in the
      presence of spiral ligament hyalinization. No significant differences were seen
      with connexin 26 immunostaining. However, immunostaining results were somewhat
      inconsistent. CONCLUSION: These data suggest that spiral ligament structure and
      function are essential for stria vascularis survival. In addition, dampened
      expression of ion transport molecules within the spiral ligament and stria
      vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear
      potential and sensory hearing loss.

PMID- 15241222
TI  - Stapes surgery in the United States.
AB  - OBJECTIVE: A contemporary analysis of trends in the surgical management of
      otosclerosis in the United States is presented. DATA SOURCES: U.S. population
      demographics were obtained from the U.S. Census Bureau. Surgical case data was
      obtained from publications of the National Center for Health Statistics.
      Physician population statistics are published by the American Medical
      Association. DATA EXTRACTION: Available estimates for otologic operations are
      interpreted according to clinical setting used for data acquisition and surgical
      practice patterns. Linear regression of included data defines trends in
      operations performed. Population statistics are used to define changes in the
      incidence of surgical cases. CONCLUSIONS: The number of stapedectomy cases has
      declined over the past 30 years. During this same interval, the U.S. population
      (including the white population) and the number of surgeons has increased. This
      indicates that the incidence of surgical otosclerosis is declining. Although the
      true etiology of the decline is uncertain, widespread immunization for measles is
      a plausible hypothesis.

PMID- 15241223
TI  - Susac syndrome.
AB  - OBJECTIVE: The objective of this study was to describe the clinical
      manifestations; radiographic, audiometric, and retinal fluorescein angiography
      findings; pathogenesis and treatment of Susac syndrome with review of the
      literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This
      study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman
      presented with recurrent episodes of neurologic symptoms, bilateral sensorineural
      hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient
      underwent complete evaluation, including magnetic resonance image studies,
      audiometric tests, and retinal fluorescein angiography. She was treated initially
      with corticosteroids and later with other immunosuppressive agents. RESULTS: The
      patient was initially diagnosed with left sudden sensorineural hearing loss.
      Despite comprehensive clinical and laboratory studies that did not reveal
      systemic disease, 3 weeks later, the patient developed vertigo, sensorineural
      hearing loss, and tinnitus in the opposite ear. The neurologic involvement and
      the bilateral audiologic manifestations raised the possibility of Susac syndrome.
      CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by
      the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting
      from microangiopathy of the brain, cochlea, and retina. The multiple organ
      involvement seen in Susac syndrome raises a differential diagnosis ranging from
      autoimmune disease, through systemic vasculitis, to multiple sclerosis.
      Otolaryngologists should be aware of this syndrome as a result of the
      vestibulocochlear manifestations and the multidisciplinary evaluation that is
      required.

PMID- 15241224
TI  - An absence of tinnitus.
AB  - We present and discuss a case of lifelong tinnitus in an otolaryngologist
      (L.D.L.) followed by complete elimination of the tinnitus as a result of a
      cerebral vascular accident located in the left corona radiata. Pre- and post-CVA
      audiograms showed no change in hearing. A magnetic resonance imaging study of the
      brain documents the size and location of the lesion. Discussion looks at recent
      studies of the central nervous system showing evidence of increased activity
      related to tinnitus. Our assessment of the lesion and the resulting loss of
      tinnitus can be explained by the neurophysiological model of tinnitus, which
      includes plasticity of the central nervous system.

PMID- 15241225
TI  - Cochlear implantation in children deafened by cytomegalovirus: speech perception
      and speech intelligibility outcomes.
AB  - BACKGROUND: Concerns have been expressed with regard to suitability for cochlear
      implantation of children deafened by cytomegalovirus because of possible
      coexisting central disorders/learning difficulties. The aim of the current study
      was to assess speech perception and intelligibility of speech produced by
      children deafened by cytomegalovirus and compare their progress with that of
      congenitally deaf children after cochlear implantation. METHODS: The study
      assessed 16 implanted children who were deafened by cytomegalovirus, using the
      Iowa Closed Sentence Test and Speech Intelligibility Rating. The results were
      compared with those of a group of 131 children who had undergone implantation who
      were congenitally deaf but did not have cytomegalovirus as the cause of deafness.
      The mean age at implantation was 3.9 years for the cytomegalovirus group (median,
      3.5 years) and 4.1 years (median, 4 years) for the congenitally deaf children.
      They all received the Nucleus multichannel cochlear implant system. The follow-up
      period ranged from 1 to 5 years after implantation for both groups. RESULTS:
      After cochlear implantation, the intelligibility of speech produced by children
      deafened by cytomegalovirus had a wide range, varying from unintelligible speech
      to connected speech intelligible to all listeners. Relative to the median score
      for the control group at the last evaluation interval, 3 of the 16 children with
      cytomegalovirus (19%) performed better, 8 children (50%) performed more poorly,
      and 5 (31%) performed the same. The difference between the two groups was not
      statistically significant (p > 0.05). With regard to speech perception Iowa
      Sentence Test (Level B), relative to the median score for the control group at
      the last evaluation interval, 5 of the 16 children with cytomegalovirus (31%)
      performed better, 3 children (19%) performed more poorly, and 8 (50%) performed
      the same. The difference between the two groups was not statistically significant
      (p > 0.05). With regard to Level A and relative to the median score for the
      control group at the last evaluation interval, 1 of the 16 children with
      cytomegalovirus (6%) performed better, 6 children (38%) performed more poorly,
      and 9 (56%) performed the same. The difference between the two groups was
      statistically significant (p = 0.04). CONCLUSION: The results of the current
      study showed that cytomegalovirus alone, as a cause of deafness, is not a
      contraindication for cochlear implantation. Parents should be informed about the
      wide range of linguistic outcomes after implantation and that these children may
      need more specific or intensive rehabilitation. Although additional problems are
      common and outcomes may, on average, be poorer, cochlear implantation can provide
      useful auditory input to these children. Further research is needed to identify
      factors associated with cytomegalovirus that may influence the outcomes.

PMID- 15241226
TI  - Simple method to control a cerebrospinal fluid gusher during cochlear implant
      surgery.
AB  - OBJECTIVE: : Perilymph/cerebrospinal fluid gushers are reported at the time of
      cochleostomy during the performance of cochlear implant surgery. Anatomic
      conditions are discussed. Surgical methods of control with tissue seals have
      varied results. A simple technique using bone-waxed silk suture is described.
      PATIENTS: : Three patients with perilymph/cerebrospinal fluid gushers were
      encountered during cochlear implant surgery in the Louisiana State University
      Cochlear Implant Project. A simple method for control of these leaks is described
      using lengths of bone-waxed silk suture. CONCLUSIONS: : This safe and rapid
      technique is a useful addition to the armamentarium of the cochlear implant
      surgeon.

PMID- 15241227
TI  - Auditory brainstem implant as a salvage treatment after unsuccessful cochlear
      implantation.
AB  - OBJECTIVE: The present article investigates on an individual basis the
      performance achieved with the auditory brainstem implant in patients who had been
      treated unsuccessfully with a cochlear implant. STUDY DESIGN: An intrasubject
      comparison between results achieved with the cochlear implant and the auditory
      brainstem implant is reported. SETTING: Tertiary referral care. PATIENTS: Five
      subjects were fitted with an auditory brainstem implant in our department because
      of the poor results achieved with cochlear implants. Two were children, one with
      bilateral cochlear nerve aplasia and one suffering from auditory neuropathy.
      Three were adults with complete cochlear ossification. INTERVENTION: A
      retrosigmoid approach was used in all subjects. Electrically evoked auditory
      brainstem responses and neural response telemetry were used to monitor electrode
      positioning. RESULTS: No complications were observed due to implantation surgery
      or related to activation or long-term use of the auditory brainstem implant.
      Auditory sensations were induced in all patients with varying numbers of
      electrodes (from 9-16). In all three adults, the cochlear implant did not allow
      either word/sentence discrimination or speech tracking, whereas the auditory
      brainstem implant permitted discrimination of two- or three-syllable words with
      scores from 85 to 100%. In the two adults with a follow-up of 5 and 6 months
      after auditory brainstem implant activation, the open-set sentence recognition
      scores (auditory-only mode) were 70% and 100%, respectively, and the speech
      tracking scores were 27 and 40 words/min, respectively. One patient with a follow
      up of only 3 months scored 0% in both sentence recognition and speech tracking.
      The two children who had achieved no hearing ability with the cochlear implant
      were already able to detect sounds and words as early as 2 months after
      activation of the auditory brainstem implant and are showing progressive
      improvement in their performance. CONCLUSION: Auditory brainstem implantation may
      be a very powerful rehabilitative treatment after cochlear implant failure. The
      possibility of using the auditory brainstem implant as first-choice therapy in
      some categories of deaf patients (e.g., subjects with auditory neuropathy or
      cochlear ossification) who are currently treated with cochlear implantation is
      discussed.

PMID- 15241228
TI  - Modifying cochlear implant design: advantages of placing a return electrode in
      the modiolus.
AB  - HYPOTHESIS: A modiolar return electrode significantly increases the current flow
      across spiral ganglion cells into the modiolus, and may decrease the cochlear
      implant's power requirements. BACKGROUND: Ideal cochlear implants should maximize
      current flow into the modiolus to stimulate auditory neurons. Previous efforts to
      facilitate current flow through the modiolus included the fabrication and use of
      precurved electrodes designed to "hug" the modiolus and silastic positioners
      designed to place the electrodes closer to the modiolus. In contrast to earlier
      efforts, this study explores the effects of return electrode placement on current
      distributions in the modiolus. METHODS: The effects of return electrode
      positioning on current flow in the modiolus were studied in a Plexiglas model of
      the cochlea. Results of model measurements were confirmed by measurements in the
      modiolus of human temporal bones. The return electrode was placed either within
      the modiolus, or remotely, outside the temporal bone, simulating contemporary
      cochlear implant configurations using monopolar stimulation. RESULTS: Cochlear
      model results clearly show that modiolar current amplitudes can be influenced
      significantly by the location of the return electrode, being larger when placed
      into the modiolus. Temporal bone data show similar findings. Voltages recorded in
      the modiolus are, on average, 2.8 times higher with the return electrode in the
      modiolus compared with return electrode locations outside the temporal bone.
      CONCLUSION: Placing a cochlear implant's return electrode in the modiolus should
      significantly reduce its power consumption. Reducing power requirements should
      lead to improved efficiency, safer long-term use, and longer device life.

PMID- 15241229
TI  - Revision cochlear implant surgery in adult patients with suspected device
      malfunction.
AB  - OBJECTIVE: To report the outcomes of patients that have undergone revision
      cochlear implant surgery for suspected device malfunction. STUDY DESIGN:
      Retrospective case series. SETTING: Academic medical center. PATIENTS: Adult
      cochlear implant patients with devices that fail to lock or maintain a lock but
      are associated with troubling signs and symptoms. INTERVENTION: Revision cochlear
      implant surgery. MAIN OUTCOME MEASURES: Demographics, presenting signs and
      symptoms, surgical findings, complications, audiologic performance and device
      analysis. RESULTS: To date, 33 revision cochlear implant operations have been
      performed in 30 patients. Eight (24%) presented with a failure of the speech
      processor to lock with the internal device (i.e., hard failure). Twenty-five
      (76%) presented with either aversive auditory (n = 23 [92%]) or nonauditory (n =
      21 [84%]) symptoms or performance-related issues (n = 16 [64%]) while maintaining
      a lock (i.e., suspected soft failure). Revision surgery resulted in resolution of
      the patient's presenting signs and symptoms in nearly 90% of cases and
      significant improvements in auditory performance. Perioperative complications
      were uncommon. Preoperative testing and device analysis frequently did not reveal
      the reason for presumed device malfunction. CONCLUSION: Revision cochlear
      implantation should be considered in patients significantly affected by
      intolerable auditory and/or nonauditory symptoms or when performance issues have
      been documented.

PMID- 15241230
TI  - The RetroX auditory implant for high-frequency hearing loss.
AB  - OBJECTIVE: The objective of this study was to analyze the subjective satisfaction
      and measure the hearing gain provided by the RetroX (Auric GmbH, Rheine,
      Germany), an auditory implant of the external ear. STUDY DESIGN: We conducted a
      retrospective case review. SETTING: We conducted this study at a tertiary
      referral center at a university hospital. SUBJECTS: We studied 10 adults with
      high-frequency sensori-neural hearing loss (ski-slope audiogram). INTERVENTION:
      The RetroX consists of an electronic unit sited in the postaural sulcus connected
      to a titanium tube implanted under the auricle between the sulcus and the
      entrance of the external auditory canal. Implanting requires only minor surgery
      under local anesthesia. MAIN OUTCOME MEASURES: Main outcome measures were a
      satisfaction questionnaire, pure-tone audiometry in quiet, speech audiometry in
      quiet, speech audiometry in noise, and azimuth audiometry (hearing threshold in
      function of sound source location within the horizontal plane at ear level).
      RESULTS: : Subjectively, all 10 patients are satisfied or even extremely
      satisfied with the hearing improvement provided by the RetroX. They wear the
      implant daily, from morning to evening. We observe a statistically significant
      improvement of pure-tone thresholds at 1, 2, and 4 kHz. In quiet, the speech
      reception threshold improves by 9 dB. Speech audiometry in noise shows that
      intelligibility improves by 26% for a signal-to-noise ratio of -5 dB, by 18% for
      a signal-to-noise ratio of 0 dB, and by 13% for a signal-to-noise ratio of +5 dB.
      Localization audiometry indicates that the skull masks sound contralateral to the
      implanted ear. Of the 10 patients, one had acoustic feedback and one presented
      with a granulomatous reaction to the foreign body that necessitated removing the
      implant. CONCLUSION: The RetroX auditory implant is a semi-implantable hearing
      aid without occlusion of the external auditory canal. It provides a new
      therapeutic alternative for managing high-frequency hearing loss.

PMID- 15241231
TI  - Unpartitioned versus incompletely partitioned cochleae: radiologic
      differentiation.
AB  - OBJECTIVE: In the process of evaluating our patients, we realized that the term
      "Mondini deformity" was being used to describe two different types of incomplete
      partition of the cochlea. THE First one consisted of an unpartitioned, completely
      empty cochlea where the interscalar septum and entire modiolus were absent,
      giving the cochlea a cystic appearance; a grossly dilated vestibule accompanied
      this lesion. The second pathology fitted the classic description of Mondini
      deformity, consisting of a normal basal turn and cystic apex (where the middle
      and apical turns form a cystic cavity), dilated vestibule, and enlarged
      vestibular aqueduct. This study was planned to investigate the differences
      between the two types of incomplete partition for inner ear malformations based
      on radiologic features. STUDY DESIGN: We conducted a retrospective review of
      temporal bone computed tomography (CT) findings. METHODS: The subjects were 18
      patients with profound bilateral sensorineural hearing loss who had high
      resolution CT with contiguous 1-mm thick images obtained through the petrous bone
      in axial sections. The CT results were reviewed as incomplete partition type I
      (IP-I) and type II (IP-II). Incomplete partition type I (unpartitioned cochlea,
      cystic cochleovestibular malformation) is defined as a malformation in which the
      cochlea lacks the entire modiolus and interscalar septa, resulting in a cystic
      appearance and there is an accompanying grossly dilated vestibule. In incomplete
      partition type II (incompletely partitioned cochlea, the Mondini deformity),
      there is a cochlea comprised of a normal basal turn and cystic apex accompanied
      by a minimally dilated vestibule and enlarged vestibular aqueduct (VA).
      Measurements involving the cochlea, vestibule, vestibular aqueduct, and internal
      auditory canal (IAC) were done to determine the characteristic features of these
      pathologies. RESULTS: : Thirteen ears had IP-I and 18 ears had IP-II anomaly. The
      size of the cochleae in both anomalies showed no significant difference from the
      normal findings. Only the internal architecture was different. All ears with IP-I
      had grossly dilated vestibules. Although both anomalies demonstrated vestibular
      dilatation, the degree of that was minimal in patients with IP-II. In IP-I
      anomalies, the IAC was larger than that in IP-II anomalies. An enlarged VA
      accompanied all cases of IP-II, whereas only one of the patients with IP-I had VA
      that could be demonstrated on CT. In all cases, the VA findings were symmetric on
      both sides: normal or enlarged. CONCLUSION: Inner ear measurements on radiologic
      findings in this study confirmed the presence of two different types of
      incomplete partition: IP-I (unpartitioned cochlea, cystic cochleovestibular
      malformation) and IP-II (incompletely partitioned cochlea, the classic Mondini
      deformity). The type I malformation is less differentiated than the type II
      malformation. Classic Mondini deformity has three components (a cystic apex,
      dilated vestibule, and large vestibular aqueduct), whereas type I malformation
      has an empty, unpartitioned cochlea and dilated vestibule without an enlarged VA.
      Mondini deformity represents a later malformation, so the degree of dysplasia is
      milder than that in type I. Not only the appearance, but also the measurements of
      the inner ear structures would be helpful in determining the type of
      malformation.

PMID- 15241232
TI  - Cochleosaccular dysplasia: a morphometric and histopathologic study in a series
      of temporal bones.
AB  - OBJECTIVE: The objective of this study was to perform a morphometric analysis of
      a series of temporal bones with cochleosaccular dysplasia to clarify the extent
      of inner ear changes in this disease. STUDY DESIGN: This human temporal bone
      histopathologic study of a series of deaf-mute cases involves morphometric
      analysis, including stria vascularis and spiral ligament area measurements and
      spiral ganglion and hair cells counts. SUBJECTS: Thirteen temporal bones were
      selected from 35 with deaf mutism based on the histopathologic findings described
      by Scheibe. Twenty normal age-matched control subjects were used for comparisons.
      RESULTS: All temporal bones had the main histopathologic findings described by
      Scheibe, as well as severe affected stria vascularis. Seven temporal bones had
      cystic areas in the stria and three had concretions. Cross-sectional strial areas
      in temporal bones with cochleosaccular dysplasia were smaller than normal in all
      cochlear turns; however, no difference was found in spiral ligament cross
      sectional areas. Reissner's membrane was hydropic in three temporal bones and the
      organ of Corti was absent in at least one cochlear turn in five. Concretions were
      present in the macula of seven temporal bones. Twelve temporal bones showed some
      level of spiral ganglion cell loss. No hair cells were observed in any temporal
      bone. A familial history of deafness was found in three cases. CONCLUSION:
      Pathologic findings were variable and limited to the saccule and scala media. The
      variation, perhaps, reflects the different etiologies involved in the origin of
      cochleosaccular dysplasia.

PMID- 15241233
TI  - Paroxetine, a selective serotonin reuptake inhibitor, reduces depressive symptoms
      and subjective handicaps in patients with dizziness.
AB  - OBJECTIVE AND STUDY DESIGN: When treating dizzy patients, the psychiatric aspect
      should be carefully addressed regardless of whether a well-defined organic
      disease is present. In this prospective study, we aimed to elucidate the role of
      paroxetine, a selective serotonin reuptake inhibitor, in the treatment of
      dizziness. SETTING AND PATIENTS: Forty-seven patients who complained of dizziness
      were treated with 20 mg of paroxetine per day. The depressive state of the
      patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment
      outcomes were measured with self-assessment of subjective handicaps in daily life
      using a dizziness and unsteadiness questionnaire. The questionnaire consisted of
      five factors related to emotional or bodily dysfunction that could be affected by
      dizziness. Changes in Self-Rating Depression Scale scores and subjective
      handicaps were assessed at 4 and 8 weeks after the start of paroxetine. RESULTS:
      In patients having well-defined organic diseases with high Self-Rating Depression
      Scale scores, paroxetine improved all five subjective handicap factors as well as
      Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale
      scores showed a significant correlation with improvement of subjective handicaps,
      which was related to emotional problems but not factors related to bodily
      dysfunction. Paroxetine was also effective for an improvement of factors related
      to emotional problems and Self-Rating Depression Scale scores in patients not
      having organic diseases but with high Self-Rating Depression Scale scores. In
      patients either with or without organic diseases with low Self-Rating Depression
      Scale scores, paroxetine had no effect on any subjective handicap factors and
      Self-Rating Depression Scale scores. CONCLUSION: In the treatment of dizzy
      patients, paroxetine was effective at relieving subjective handicaps caused by
      dizziness, specifically, in patients with high Self-Rating Depression Scale
      scores.

PMID- 15241234
TI  - Intratympanic gentamicin therapy for Meniere's disease: a meta-analysis.
AB  - OBJECTIVE: This study compared the effectiveness of five different techniques of
      intratympanic gentamicin administration for Meniere's disease. DATA SOURCES: A
      MEDLINE search of the English language literature from 1978 to 2002 was performed
      using the key words "intratympanic," "gentamicin," "therapy," "Meniere's," and
      "disease." STUDY SELECTION: Inclusion criteria to select articles for meta
      analysis were clear description of gentamicin delivery technique, clearly
      reported vertigo control results, and report of hearing loss posttreatment. Seven
      studies (n = 218) describing the multiple daily dosing technique (delivery three
      times per day for >or=4 d), two studies (n = 84) describing the weekly dosing
      technique (weekly injections for four total doses), eight studies (n = 253) of
      the low-dose technique (one to two injections with retreatment for recurrent
      vertigo), four studies (n =156) of continuous microcatheter delivery, and six
      studies (n =269) of the titration technique (daily or weekly doses until onset of
      vestibular symptoms, change in vertigo, or hearing loss) were entered into the
      model. DATA EXTRACTION: Vertigo control results were stratified into complete,
      substantial, or poor control. Hearing results were separated by profound,
      partial, or no hearing loss. Individuals undergoing caloric testing were
      separated by degree of vestibular ablation (complete versus partial) and analyzed
      for vertigo control (n = 301) and hearing loss (n = 333) after treatment. DATA
      SYNTHESIS: Comparisons between the rates of complete vertigo control, effective
      vertigo control (complete plus substantial control), overall hearing loss
      (partial plus profound), and profound hearing loss by delivery method were based
      on a parametric empirical Bayes analysis using binomial generalized linear models
      and backward variable selection (joining). Relative risk for vertigo control and
      hearing loss by partial or complete ablation was examined study by study using
      residual maximum likelihood to carry out a parametric empirical Bayes analysis.
      CONCLUSION: The titration method of gentamicin delivery demonstrated
      significantly better complete (81.7%, p = 0.001) and effective (96.3%, p < 0.05)
      vertigo control compared with other methods. The low-dose method of delivery
      demonstrated significantly worse complete vertigo control (66.7%, p < 0.001) and
      trends toward worse effective vertigo control (86.8%, p = 0.05) compared with
      other methods. The weekly method of delivery trends toward less overall hearing
      loss (13.1%, p = 0.08), and the multiple daily method demonstrated significantly
      more overall hearing loss (34.7%, p < 0.01) compared with other groups. No
      significant difference in profound hearing loss was found between groups. Degree
      of vestibular ablation after gentamicin therapy is not significantly correlated
      with the resulting vertigo control or hearing loss status.

PMID- 15241235
TI  - Effects of hyperbaric therapy on function and morphology of Guinea pig cochlea
      with endolymphatic hydrops.
AB  - OBJECTIVE: The objective of this study was to investigate the effect on
      experimental endolymphatic hydrops in guinea pigs after hyperbaric therapy.
      BACKGROUND: The histopathologic character of Meniere's disease is the presence of
      endolymphatic hydrops. Endolymphatic hypertension could be one of the factors
      resulting from endolymphatic hydrops. Some treatments of Meniere's disease are
      aimed toward preventing the endolymphatic hypertension. Exposure to pressure
      change has risen in recent years. METHODS: Thirty-two guinea pigs were operated
      on the right ears to induce endolymphatic hydrops by obliterating the
      endolymphatic sac through an extradural posterior cranial fossa approach. After 5
      weeks' survival, 12 guinea pigs were put into a chamber with an absolute
      atmospheric pressure of 2.2 for 3 weeks (90 minutes once a day 5 times a week).
      We observed the morphologic and functional changes in guinea pig cochleae of the
      pressure group, 4-week hydrops group (n = 10), 8-week hydrops group (n = 10), and
      the normal group (n = 10). We measured the hearing threshold of the auditory
      brainstem response, the 70-dB SPL action potential (AP) latency, the ratio of 70
      dB SPL summating potential magnitude to action potential magnitude (-SP/AP) of
      the electrocochleogram, and the maximum scala media area (SMA) ratio,
      respectively. RESULTS: The average 70-dB SPL-SP/AP magnitude of right ears (0.29
      +/- 0.09) and the average maximum SMA ratio (2.23 +/- 0.20) in the pressure group
      were significantly less than that in the 8-week hydrops group (0.69 +/- 0.15 and
      4.04 +/- 0.52, respectively) with the same survival time (p < 0.05). The results
      in the pressure group were almost as similar as that in the 4-week hydrops group
      (0.29 +/- 0.13 and 2.22 +/- 0.20, respectively) (p > 0.05). The average hearing
      threshold of ABR of right ears in the pressure group (36.67 +/- 14.30-dB SPL) was
      lower than that of the 8-week hydrops group (44 +/-1 4.30-dB SPL), but the
      difference was insignificant (p > 0.05). The average 70-dB SPL AP latency of
      right ears in the pressure group was not significantly different from those of
      the 8-week hydrops group, the 4-week hydrops group, or the normal group (p >
      0.05). CONCLUSIONS: Our findings suggest hyperbaric therapy can significantly
      suppress the development of endolymphatic hydrops and improve cochlear function
      in guinea pigs. This study provided strong evidence for the development of
      pressure treatment of Meniere's disease without destroying the inner ear.

PMID- 15241237
TI  - Transjugular craniotomy for the management of jugular foramen tumors with
      intracranial extension.
AB  - OBJECTIVES: To elucidate indications and outcomes with the transjugular
      craniotomy for resection of jugular foramen tumors with intracranial extension.
      The transjugular approach is a lateral craniotomy conducted through a partial
      petrosectomy traversing the jugular fossa combined with resection of the sigmoid
      sinus and jugular bulb, which often have been occluded by disease. STUDY DESIGN:
      Retrospective review. SETTING: University medical center. PATIENTS: Twenty-eight
      patients with intracranial jugular foramen tumors who underwent a total of 30
      surgical procedures. MAIN OUTCOME MEASURES: Pathologic findings, surgical
      approach, extent of tumor resection, rate of facial nerve mobilization and ear
      canal closure, facial and lower cranial nerve outcomes, and hearing preservation.
      RESULTS: Tumors included schwannoma (37%), meningioma (33%), glomus jugulare
      (23%), and chordoma (7%). The surgical approaches were tailored to maximize
      functional preservation, and included the transjugular (53%), translabyrinthine
      (17%), retrosigmoid (10%), and far lateral (7%) craniotomies. Translabyrinthine
      (3%) or transcondylarfar lateral (3%) approaches were occasionally used in
      combination with the trans-jugular approach. Most procedures were managed in a
      single stage (90%), but three patients with massive tumor in the neck required
      two stages. Microsurgical gross total and near-total tumor removal (37% each)
      were commonly achieved, although subtotal resections (27%) were occasionally
      performed. In only a minority of cases was facial nerve mobilization (7%) or ear
      canal closure (21%) required. If present preoperatively, Grade I facial nerve
      function was usually maintained (22 of 24 [92%]) and Hearing Class A or B could
      always be maintained (9 of 9 [100%]). As expected, new lower cranial nerve
      dysfunction was common (8 of 30 [27%]), although over half of the patients had
      complete lower nerve palsy preoperatively (16 of 30 [53%]). CONCLUSION: Most
      patients with jugular foramen tumors with intracranial extension can be managed
      with a single-stage transjugular craniotomy. Facial nerve mobilization or ear
      canal closure is usually not required, permitting conservation of facial function
      and hearing, when present preoperatively.

PMID- 15241236
TI  - Permanent gentamicin vestibulotoxicity.
AB  - OBJECTIVE: To determine the natural history of permanent gentamicin
      vestibulotoxicity. STUDY DESIGN: Retrospective; comparison of retrospective and
      prospective studies. SETTING: Tertiary neurotology clinic. Clinical research and
      technology center. SUBJECTS: Thirty-three subjects with permanent gentamicin
      induced vestibulotoxicity. INTERVENTIONS: Medical records review, neurotologic
      examination, and vestibular and auditory function tests. MAIN OUTCOME MEASURES:
      Vestibular and auditory function test results at least 1 year after
      discontinuation of gentamicin, clinical examination results, serum gentamicin
      levels, and serum creatinine levels. RESULTS: Thirty-three subjects had
      vestibular function test results consistent with permanent gentamicin
      ototoxicity. All complained of dysequilibrium, 32 described oscillopsia, and 23
      had tinnitus. All 33 subjects had complained of symptoms consistent with
      ototoxicity within 1 to 3 weeks of initiation of gentamicin therapy; however,
      gentamicin vestibulotoxicity was not recognized before hospital discharge in 32
      of 33 subjects. Serum peak and trough gentamicin levels did not correlate with
      the development of vestibulotoxicity, nor did observance of recommended "safe"
      dosage ranges. Of 17 subjects whose serum creatinine levels were recorded, 6
      experienced abnormal elevations in serum creatinine in conjunction with
      gentamicin use. CONCLUSION: Gentamicin can cause permanent vestibular and
      auditory ototoxicity. There is no safe dose of gentamicin. Serum gentamicin
      levels are of no value in predicting the onset, occurrence, or severity of
      vestibulotoxicity or cochleotoxicity. Termination of gentamicin on appearance of
      signs or symptoms of ototoxicity may reduce the incidence of permanent vestibular
      ototoxicity. When possible, other antibiotics should be administered.

PMID- 15241238
TI  - Management options for cerebrospinal fluid leak after vestibular schwannoma
      surgery and introduction of an innovative treatment.
AB  - OBJECTIVE: To review the management of cerebrospinal fluid leak after vestibular
      schwannoma removal reported in the literature and to present a novel approach to
      management of recalcitrant cases. DATA SOURCES: MEDLINE and PubMed literature
      search using the terms "cerebrospinal fluid leak" or "cerebrospinal fluid
      fistula" and "acoustic neuroma" or "vestibular schwannoma" covering the period
      from 1985 to present in English. A review of bibliographies of these studies was
      also performed. STUDY SELECTION: Criteria for inclusion in this meta-analysis
      consisted of the availability of extractable data from studies presenting a
      defined group of patients who had undergone primary vestibular schwannoma removal
      and for whom the presence and absence of cerebrospinal fluid leakage was
      reported. Studies reporting combined approaches were excluded. No duplications of
      patient populations were included. Twenty-five studies met the inclusion
      criteria. DATA EXTRACTION: Quality of the studies was determined by the design of
      each study and the ability to combine the data with the results of other studies.
      All of the studies were biased by their retrospective, nonrandomized nature. DATA
      SYNTHESIS: Significance (p < 0.05) was determined using the chi test.
      CONCLUSIONS: Incisional cerebrospinal fluid leakage responded well to local
      management and lumbar drainage. Rhinorrhea often necessitated surgical
      intervention. No specific reoperation techniques correlated exclusively with
      better reoperation outcomes. The transaural/transnasal approach presents an
      alternative for surgical management of cerebrospinal fluid rhinorrhea.

PMID- 15241239
TI  - Serial analysis of gene expression in neurofibromatosis type 2-associated
      vestibular schwannoma.
AB  - HYPOTHESIS: The genesis, morphology, and growth characteristics of vestibular
      schwannomas are determined by genetic alterations which vary gene transcript
      expression and this transcript expression can be qualitatively and quantitatively
      evaluated using the SAGE technique. By use of such technique, gene products with
      tumorigenic potential may be identified, providing insight and targets for future
      study. BACKGROUND: Serial analysis of gene expression (SAGE) is a powerful new
      technique that allows detailed qualitative and quantitative evaluation of
      cellular gene transcript expression. Tissue in limited quantity (5 x 10 to 2 x 10
      cells) may be analyzed by a modified version of SAGE called microSAGE.
      Application of SAGE or microSAGE to study vestibular schwannoma gene expression
      has not been previously reported. METHODS: Fresh, vestibular schwannoma specimen
      from an individual with the diagnosis of neurofibromatosis type 2 was attained
      intraoperatively and maintained in a sealed container at -80degreesC until the
      time of analysis. The tissue was processed according to the microSAGE protocol,
      using 180 mg of vestibular schwannoma as starting material. RESULTS: The protocol
      resulted in the generation and sequencing of a tag library involving 458 tags
      representing 277 different gene products, including many transcripts known to be
      expressed in vestibular schwannomas. Several gene products with tumorigenic
      potential were identified. CONCLUSIONS: These data demonstrate that microSAGE is
      a useful technique to study vestibular schwannoma gene expression. Future studies
      will include building more comprehensive libraries and comparing libraries from
      various vestibular schwannoma phenotypes to identify useful diagnostic or
      prognostic markers, and targets for therapeutic intervention.

PMID- 15241240
TI  - Hearing preservation with the transcrusal approach to the petroclival region.
AB  - OBJECTIVE: We studied the hearing results and outcomes after transcrusal
      craniotomy. STUDY DESIGN: We conducted a retrospective review. SETTING: This
      study was conducted at a tertiary care hospital. PATIENTS: We studied 10
      consecutive patients, including two men and eight women, who underwent
      transcrusal craniotomy for petroclival masses or tumors. INTERVENTION: The
      intervention consisted of therapeutic removal of petroclival meningioma. MAIN
      OUTCOME MEASURE: The main outcome measure of this study was hearing preservation
      as measured by standard audiogram. RESULTS: There were six meningiomas, one
      eighth nerve schwannoma, one fifth nerve schwannoma, one chordoma, and one
      midbasilar artery aneurysm. Postoperative hearing was measured according to the
      AAOHNS criteria. Complications and further therapies were recorded. Postoperative
      hearing was measured in eight. The cochlear nerve was severed in one patient. One
      was unavailable for follow up. Eight patients retained hearing at or near
      preoperative levels, seven with SRT within 10 dB and speech discrimination within
      10% of preoperative levels. Four patients presented with trigeminal symptoms, one
      with third nerve palsy and two with facial weakness. Postoperative deficits
      included fourth, sixth, seventh, and eighth nerve palsies in three patients.
      Complications included one wound infection, two cerebrospinal fluid leak, and two
      cases of meningitis, both of which were sterile. There were secondary procedures
      in five patients-three radiosurgery, two shunts, one tracheotomy, and one g-tube.
      CONCLUSIONS: Transcrusal craniotomy is a safe and effective approach to the
      petroclival region. Excellent hearing results can be expected with this
      technique.

PMID- 15241241
TI  - Endolymphatic sac tumors: a review of the St. Vincent's hospital experience.
AB  - OBJECTIVE: To describe the clinical, radiologic and histopathologic features of
      endolymphatic sac tumors using the St Vincent's Hospital experience with these
      tumors to highlight important aspects of tumor diagnosis and treatment. Possible
      explanations are given for the apparent increasing incidence of these tumors.
      STUDY DESIGN: Retrospective review of the senior author's (P.A.F.) database of
      skull base lesions. SETTING: Tertiary referral teaching hospital. PATIENTS: All
      patients with a proven diagnosis of endolymphatic sac tumor treated at St
      Vincent's Hospital, Sydney. OUTCOME MEASURES: Survival in months, after surgery.
      RESULTS: Seven cases of endolymphatic sac tumors. All were treated surgically.
      Mean follow-up of 70.2 months (range, 6-144 mo). CONCLUSION: Endolymphatic sac
      tumors are becoming increasingly recognized because of awareness of their
      existence as a separate entity from middle ear tumors. This has been achieved by
      improved imaging and histopathologic techniques. Surgery is the mainstay of
      treatment.

PMID- 15241242
TI  - Complication rate of transtemporal hydroxyapatite cement cranioplasties: a case
      series review of 76 cranioplasties.
AB  - OBJECTIVE: The objective of this study was to evaluate the complication rate of
      transtemporal cranioplasties using hydroxyapatite cement (HAC) for repair. STUDY
      DESIGN: We conducted a retrospective case review of patients receiving HAC
      cranioplasties in the Acoustic Neuroma and Skull Base Surgery Program between
      July 1998 and December 2002. SETTING: This study was conducted at a tertiary
      referral center. PATIENTS: A total of 76 HAC cranioplasties were performed in 72
      patients undergoing lateral skull base surgery. Patients undergoing anterior
      skull base surgery or those in which HAC was used for other reconstructive
      purposes were excluded from the study. INTERVENTIONS: We studied transtemporal
      approaches for otologic procedures requiring cranioplasty. MAIN OUTCOME MEASURES:
      Main outcomes measures consisted of complications requiring medical or surgical
      intervention. RESULTS: Of the 76 HAC cranioplasties, two cranioplasty grafts
      became infected, requiring explantation. The first case involved a wound
      infection that extended into and involved the HAC graft; the second involved
      seeding of the HAC graft after meningitis after a percutaneous, endoscopic
      gastrostomy tube placement performed several days after the primary skull base
      surgery. This gives our series a wound infection incidence rate of 1.3% and an
      overall complication incidence rate of 2.63%. CONCLUSIONS: This retrospective
      review provides the largest series to date evaluating the incidence of infection
      in HAC cranioplasties. Despite having a much larger series, our complication rate
      is the lowest published rate of HAC cranioplasty explantation, and the incidence
      of superficial wound infections reported here is consistent with the published
      data for neurosurgical and neurotologic procedures.

PMID- 15241243
TI  - Destructive, granulating lesion in the temporal bone after elevated plasma
      homocysteine.
AB  - OBJECTIVE: This is a presentation of a seemingly new otolaryngologic disease.
      SETTING: This study was conducted at a tertiary referral center. CASE REPORT: A
      38-year-old healthy man developed left-sided sudden deafness with vertigo and
      temporary left facial palsy. A granulating and destructive lesion in the left
      temporal bone was discovered; repeated histologic examination only showed simple
      granulation tissue. After 6 months, a part of the bony cochlea was extruded. With
      approximately 8 months' delay and after the patient had had postoperative lung
      embolism, plasma homocysteine was found to be significantly elevated, a condition
      known as an independent risk factor for thromboembolic lesions. In the acquired
      form, it is most often caused by nutritional deficiency of vitamin B cofactors.
      Accordingly, the patient was treated with folic acid, which rapidly normalized
      plasma homocysteine. Subsequently, the granulation tissue in the temporal bone
      gradually disappeared, clinically and radiologically, and the lesion healed,
      obviously without cochlea function. CONCLUSIONS: Thromboembolic lesion in the
      left temporal bone, probably in the thin end artery a. labyrintina, i.e., an
      avascular osteonecrosis. During the latest years, an association between
      avascular osteonecrosis (most often in the hip) and conditions with increased
      risk of thrombosis such as hyperhomocystinemia has been established but, to the
      best of our knowledge, it is never with a lesion in the temporal bone.

PMID- 15241244
TI  - Chronic pachymeningitis presenting as asymmetric sensorineural hearing loss.
AB  - OBJECTIVE: The objective of this study was to characterize the auditory
      dysfunction associated with chronic pachymeningitis (inflammation of the dura
      mater). STUDY DESIGN AND SETTING: We conducted a university-based retrospective
      review. RESULTS: Three patients were identified who were diagnosed with chronic
      pachymeningitis after being referred for asymmetric sensorineural hearing loss.
      All patients were found to have other neurologic symptoms and signs during
      careful neurotologic evaluation. Two varieties of chronic pachymeningitis exist:
      a hypertrophic mass lesion and a linear dural thickening. Although the
      hypertrophic variety could be easily detectable by noncontrast magnetic resonance
      imaging (MRI), the linear form is only visible with the use of gadolinium
      enhancement. CONCLUSION: Chronic pachymeningitis is a rare form of sensorineural
      hearing loss that could portend an underlying disease of greater concern.
      Extensive evaluation is needed to exclude identifiable causes of chronic
      pachymeningitis, including infectious, neoplastic, and autoimmune diseases.
      SIGNIFICANCE: The clinician should be aware that the evaluation of a patient with
      asymmetric sensorineural hearing loss involves more than simply ruling out an
      acoustic neuroma. Fast-spin echo MRI techniques without the use of gadolinium
      contrast could miss a number of potentially treatable diseases such as chronic
      pachymeningitis. Patients with asymmetric sensorineural hearing loss should be
      carefully evaluated for other neurologic findings, and imaging with enhanced MRI
      is recommended.

PMID- 15241245
TI  - Preoperative appearance of facial muscles on magnetic resonance predicts final
      facial function after acoustic neuroma surgery.
AB  - OBJECTIVE: Several previous studies have shown that muscle appearance on magnetic
      resonance is a sensitive indicator of muscle denervation. Previous attempts at
      determining preoperative indicators of final facial function after acoustic
      neuroma removal has been mostly unsuccessful. The goal of this study was to
      determine if the appearance of the facial muscles on preoperative imaging is
      predictive of final facial function after surgical removal of vestibular
      schwannomas. STUDY DESIGN: We conducted a retrospective chart and magnetic
      resonance review. SETTING: This study was conducted at a tertiary referral
      center. PATIENTS: We included all patients who underwent vestibular schwannoma
      removal between January 1, 1997, and December 31, 2001, with available
      preoperative magnetic resonance images and a minimum of 12 months follow up.
      INTERVENTIONS: We used translabyrinthine, middle fossa, and suboccipital
      approaches for tumor removal. A neuroradiologist, blinded to preoperative or
      final facial function after tumor removal, retrospectively reviewed preoperative
      magnetic resonance images. MAIN OUTCOMES MEASURES: Facial muscles were evaluated
      on magnetic resonance and classified as symmetric or asymmetric. Facial function
      was graded using the House-Brackmann scale. Preoperative facial function was
      noted on the preoperative physical examination. Final function was determined at
      least 12 months postoperatively. RESULTS: A total of 247 patients underwent tumor
      removal during the study period. One hundred thirty-two patients had adequate
      preoperative magnetic resonance images. Patients with preoperative facial muscle
      asymmetry seen on preoperative magnetic resonance indicating muscle atrophy had
      significantly worse final facial function, regardless of tumor size. CONCLUSION:
      The preoperative appearance of facial muscles provides valuable insight into the
      physiology of the facial nerve in the presence of vestibular schwannomas.
      Patients with pre-operative facial muscle symmetry have significantly better
      facial function than those with atrophy.

PMID- 15241246
TI  - Caspases, the enemy within, and their role in oxidative stress-induced apoptosis
      of inner ear sensory cells.
AB  - This review covers the general roles of members of the cysteine protease family
      of caspases in the process of apoptosis (programmed cell death) looking at their
      participation in both the "extrinsic" cell death receptor and the "intrinsic"
      mitochondrial cell death pathways. It defines the difference between initiator
      and effector caspases and shows the progression of caspase activations that ends
      up in the apoptotic cell death and elimination of a damaged cell. The review then
      presents what is currently know about the participation of caspases in the
      programmed cell death of inner ear sensory cells during the process of normal
      development and maturation of the inner ear and their importance in this process
      as illustrated by the results of caspase-3 gene knockout experiments. The
      participation of specific caspases and the sequence of their activation in the
      elimination (apoptosis) of damaged sensory cells from adult inner ears after an
      injury that generates oxidative stress are reviewed. Both the possibility and the
      potential efficacy of caspase inhibition with a broad-spectrum pancaspase
      inhibitor as an interventional therapy to treat and rescue oxidative stress
      damaged inner ear sensory cells from apoptosis are presented and discussed.

PMID- 15241247
TI  - Enhancement of the otic capsule in active retrofenestral otosclerosis.

PMID- 15241248
TI  - Temporal bone osteopetrosis.

PMID- 15241249
TI  - Molecular pathogenesis of skull base tumors.
AB  - OBJECTIVE: To review contemporary molecular biological literature related to
      skull base tumor biology and tumorigenesis. DATA SOURCES: PUBMED and Ovid
      literature searches were performed using keyword search. Only English language
      articles published between 1965 and December 4, 2003 were chosen. STUDY SELECTION
      AND DATA EXTRACTION: All relevant articles from the past 8 years, as well as
      landmark articles in years before 1995, were retrieved and reviewed. CONCLUSION:
      Consistent progress is being made toward the molecular genetic and biological
      basis of the most common skull base tumors. An understanding of these mechanisms
      will aid the neurotologist in future diagnosis and management of the lesions.

PMID- 15241263
TI  - Getting the lowdown on herpetic whitlow.

PMID- 15241264
TI  - Tips for inserting an i.v. in an older patient.

PMID- 15241265
TI  - Why hold the metformin?

PMID- 15241269
TI  - Inserting an indwelling urinary catheter in a male patient.

PMID- 15241274
TI  - Documenting known or suspected medical device failure.

PMID- 15241275
TI  - Improving practice with a journal club.

PMID- 15241285
TI  - Act fast when your patient has dyspnea.

PMID- 15241286
TI  - When is a table an umbrella?

PMID- 15241287
TI  - Use bispectral index to gauge consciousness.

PMID- 15241290
TI  - The role of bacterial toxins in wounds.

PMID- 15241291
TI  - Shortcut to peritonitis.

PMID- 15241292
TI  - Hypertensive emergency.

PMID- 15241293
TI  - Assessing current practice in Alzheimer's disease.

PMID- 15241294
TI  - What is the rationale for new treatment strategies in Alzheimer's disease?
AB  - Alzheimer's disease (AD) is characterized by the abnormal extracellular
      accumulation of amyloid beta-peptide (Abeta) into neuritic plaques and the
      intraneuronal aggregation of the microtubule-associated protein tau to form
      neurofibrillary tangles. These molecular events are implicated in the selective
      damage to neural systems critical for the brain functions that are impaired in
      AD. Impairment of cholinergic neurotransmission may be an important factor
      underlying the defects in cognition and memory that characterize AD.
      Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and
      galantamine, cause symptomatic improvement by inhibiting the breakdown of the
      neurotransmitter acetylcholine to increase its synaptic availability and, in the
      case of galantamine, by also allosterically potentiating nicotinic cholinergic
      receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and
      statins, have shown some benefit in epidemiological studies and clinical trials
      although compelling evidence of their efficacy is lacking. Memantine, shown to
      cause cognitive and functional improvement, is not an ChE inhibitor and does not
      interact with marketed ChE inhibitors. While the mechanism of action of memantine
      in AD is not known, the principal pharmacologic actions at therapeutic dose are
      inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D
      aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists,
      memantine causes behavioral activation associated with enhanced cerebral glucose
      utilization. Studies have shown that memantine can reverse the decreased
      metabolic activity associated with AD, possibly accounting for its beneficial
      effects on cognition and global functioning. Memantine also has neuroprotective
      properties and can inhibit Abeta-induced neurodegeneration.

PMID- 15241295
TI  - What are the challenges faced by psychiatrists in the management of Alzheimer's
      disease?
AB  - Alzheimer's disease (AD) is a debilitating condition affecting millions of
      elderly citizens. The quality of life for AD patients significantly deteriorates
      in the face of worsening cognitive deficits and disabling functional declines,
      both contributing to manifestations of difficult behaviors. Of the estimated 4
      million individuals with AD, only 60% of probable AD cases are diagnosed, with
      little more than half of those receiving treatment. One of the possible reasons
      for this problem is the large role primary care physicians (PCPs) have in
      diagnosing and treating AD. The barriers that PCPs confront to adequately manage
      these patients will be discussed. Finally, the specific challenges that geriatric
      psychiatrists will face in addressing these issues in an environment where there
      is only a limited number of trained geriatric psychiatrists will be discussed, as
      well as the possible role that new technology could have in finding the solution
      to this difficult problem.

PMID- 15241296
TI  - What does imaging add to the management of Alzheimer's disease?
AB  - The prevalence of Alzheimer's disease (AD) and dementia continues to rise.
      However, a significant number of patients are undiagnosed or untreated. Given the
      complexities of detecting cognitive impairment and the early signs of AD, this
      review discusses how advances in brain imaging can help assist in improving
      overall management. Imaging techniques and surrogate markers may provide unique
      opportunities to diagnose accurately AD in presymptomatic stages with practical
      consequences for patients, caregivers, and physicians. The possible outcomes for
      using imaging and surrogate markers as adjuncts to clinical examination and as
      screening tools for AD, as well as tangible and intangible advantages to early
      diagnosis and treatment, will be discussed. The specific value of using advanced
      serial imaging in patients with a genetic disposition to AD will be evaluated. If
      neurons can be protected from neurodegenerative damage in early stages, this may
      preserve patient cognition, function, and quality of life, and may confer
      considerable societal healthcare benefits.

PMID- 15241297
TI  - Understanding the latest advances in pharmacologic interventions for Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a complex medical condition involving abnormalities
      in multiple biological and environmental domains. Current knowledge suggests that
      simultaneous intervention in these domains may be the most effective way to help
      AD patients and their families. Treatments for AD are centered on the inhibition
      of enzymes responsible for the degradation of acetylcholine--a neurotransmitter
      that is reduced in AD patients. Four cholinesterase inhibitors have been approved
      by the United States Food and Drug Administration, three of which are routinely
      used for the symptomatic treatment of mild-to-moderate AD. Strategies will be
      reviewed with regard to cognitive, functional, and behavioral domains. Providing
      a different treatment option for patients with AD, memantine is a low-to-moderate
      affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has
      been approved for the treatment of moderate-to-severe AD. The clinical efficacy
      and tolerability of memantine monotherapy and combination therapy in patients
      with AD will be presented. Finally, the role of nonpharmacologic intervention
      will be discussed.

PMID- 15241298
TI  - Trends in primary and secondary syphilis and HIV infections in men who have sex
      with men--San Francisco and Los Angeles, California, 1998-2002.
AB  - Because syphilis infection facilitates acquisition and transmission of human
      immunodeficiency virus (HIV), recent outbreaks of syphilis among men who have sex
      with men (MSM) in major U.S. cities, including San Francisco and Los Angeles, and
      reported increases in sexual risk behavior have raised concerns about potential
      increases in HIV transmission. In 2002, MSM accounted for the majority of primary
      and secondary (P&S) syphilis cases in men reported in San Francisco (93%) and Los
      Angeles (81%). To investigate a potential change in HIV incidence associated with
      the syphilis outbreaks in the two cities, local, state, and federal health
      officials analyzed data from HIV counseling and testing centers and a municipal
      sexually transmitted disease (STD) clinic. This report describes the results of
      that investigation, which indicated that, as of 2002, the outbreaks of syphilis
      had not had a substantial impact on HIV incidence among MSM in these two cities.
      However, the continued increase in syphilis cases in MSM underscores the need for
      integrated HIV- and STD-prevention strategies to control syphilis outbreaks and
      prevent potential increases in HIV infections (6,7) and for further systematic
      studies of HIV incidence among MSM infected with syphilis.

PMID- 15241299
TI  - Adult blood lead epidemiology and surveillance--United States, 2002.
AB  - CDC's state-based Adult Blood Lead Epidemiology and Surveillance (ABLES) program
      tracks laboratory-reported blood lead levels (BLLs) in adults. A national health
      objective for 2010 is to reduce to zero the number of adults with BLLs >/=25
      microg/dL (objective no. 20-07). A second key ABLES measurement is BLLs >/=40
      microg/dL, the level under which the Occupational Safety and Health
      Administration allows workers to return to work after being removed with an
      elevated BLL, and the level under which an annual medical evaluation of health
      effects related to lead exposure is required. The most recent ABLES report
      provided data collected during 1994-2001. This report presents ABLES data for
      2002, the first year that individual rather than summary data were collected. The
      2002 data indicate that approximately 95% of adult lead exposures were
      occupational, 94% of those exposed were male, and 91% were aged 25-64 years. The
      findings also indicated that the national decline in the number of adults with
      elevated BLLs continued in 2002; however, even greater prevention activities,
      particularly in work environments, will be necessary to achieve the 2010 health
      objective.

PMID- 15241300
TI  - Lead poisoning associated with ayurvedic medications--five states, 2000-2003.
AB  - Although approximately 95% of lead poisoning among U.S. adults results from
      occupational exposure, lead poisoning also can occur from use of traditional or
      folk remedies. Ayurveda is a traditional form of medicine practiced in India and
      other South Asian countries. Ayurvedic medications can contain herbs, minerals,
      metals, or animal products and are made in standardized and nonstandardized
      formulations. During 2000-2003, a total of 12 cases of lead poisoning among
      adults in five states associated with ayurvedic medications or remedies were
      reported to CDC. This report summarizes these 12 cases. Culturally appropriate
      educational efforts are needed to inform persons in populations using traditional
      or folk medications of the potential health risks posed by these remedies.

PMID- 15241301
TI  - Childhood lead poisoning from commercially manufactured French ceramic dinnerware
      -New York City, 2003.
AB  - Lead poisoning adversely affects children worldwide. During 1999-2000, an
      estimated 434,000 children aged 1-5 years in the United States had elevated blood
      lead levels (BLLs) >/=10 microg/dL. Glazes found on ceramics, earthenware, bone
      china, and porcelain often contain lead and are a potential source of lead
      exposure. Children are especially vulnerable to the neurotoxic effects of lead.
      Exposures to lead in early childhood can have adverse effects on the developing
      nervous system, resulting in decreased intelligence and changes in behavior. In
      addition, certain behaviors (e.g., thumb sucking) place children at greater risk
      for exposure to lead. In 2003, the New York City Department of Health and Mental
      Hygiene's Lead Poisoning Prevention Program (LPPP), and the Mount Sinai Pediatric
      Environmental Health Specialty Unit (PEHSU) investigated a case of lead poisoning
      in a boy aged 20 months. This report summarizes that case investigation, which
      identified ceramic dinnerware imported from France as the source of lead
      exposure. This case underscores the susceptibility of children to a toxic
      exposure associated with 1) the high proportion of time spent in the home and 2)
      dietary habits that promote exposure to lead leached from ceramic ware.

PMID- 15241302
TI  - West Nile virus activity--United States, June 30-July 6, 2004.
AB  - During June 30-July 6, a total of 21 human cases of West Nile virus (WNV) illness
      were reported from two states (Arizona and California). During 2004, eight states
      have reported a total of 78 human cases of WNV illness to CDC through ArboNET. Of
      these, 57 (73%) were reported from Arizona. Forty-seven (61%) of the 78 cases
      occurred in males; the median age of patients was 53 years (range: 1-84 years);
      the dates of illness onset ranged from April 23 to June 28; and one case was
      fatal.

PMID- 15241303
TI  - Investigation of rabies infections in organ donor and transplant recipients-
      Alabama, Arkansas, Oklahoma, and Texas, 2004.
AB  - On June 30, 2004, CDC confirmed diagnoses of rabies in three recipients of
      transplanted organs and in their common donor, who was found subsequently to have
      serologic evidence of rabies infection. The transplant recipients had
      encephalitis of unknown etiology after transplantation and subsequently died.
      Specimens were sent to CDC for diagnostic evaluation. This report provides a
      brief summary of the ongoing investigation and information on exposure risks and
      postexposure measures.

PMID- 15241305
TI  - Right and left knee laxity measurements: a prospective study of patients with
      anterior cruciate ligament injuries and normal control subjects.
AB  - PURPOSE: The purpose of this study was to analyze and compare knee laxity in a
      group of patients with a unilateral right anterior cruciate ligament (ACL)
      rupture and a group of patients with a unilateral left ACL rupture. Another goal
      was to analyze and compare the knee laxity of the right and left knees in a group
      of persons without any known knee problems. TYPE OF STUDY: Prospective
      examination of the same patients preoperatively and 2 years after the
      reconstruction with examination of the healthy controls at 2 different occasions.
      METHODS: Group A was composed of 41 patients with a right-sided chronic ACL
      rupture, and group B was composed of 44 patients with a left-sided chronic ACL
      rupture. All patients underwent an arthroscopic ACL reconstruction using patellar
      tendon autograft. Group C was composed of 35 persons without any known knee
      problems. One experienced physiotherapist performed all the KT-1000 measurements
      and the clinical examinations. RESULTS: Group A displayed an increased difference
      in side-to-side laxity between the injured and non-injured side compared with
      group B in terms of both anterior and total knee laxity. This difference was
      found to be statistically significant preoperatively (P =.01, anterior; P =.001,
      total) and at follow-up evaluation 2 years after the index surgery (P =.008,
      anterior; P =.006, total). In group C, a significant increase was seen in
      absolute anterior and total laxity in the right knee compared with the left knee
      when 2 repeated measurements were performed (P <.0001 and P =.003, anterior; P
      <.0001 and P =.001, total). CONCLUSIONS: The KT-1000 arthrometer revealed a
      significant increase in laxity measurements in right knees compared with left
      knees. This difference was found both preoperatively and postoperatively in
      patients undergoing ACL reconstruction. The same thing was found in a group of
      persons without any known knee problems. LEVEL OF EVIDENCE: Level II.

PMID- 15241306
TI  - The effect of early motion on tibial tunnel widening after anterior cruciate
      ligament replacement using hamstring tendon grafts.
AB  - PURPOSE: The purpose of this study was to evaluate the hypothesis that early
      motion increases tibial tunnel enlargement in patients who underwent anterior
      cruciate ligament (ACL) replacement with hamstring autograft. TYPE OF STUDY:
      Cohort analytic study. METHODS: All patients in this study had received a doubled
      semitendinous and gracilis graft. Grafts were secured in place with an implant
      free technique. Two groups of patients were evaluated. Group A consisted of 35
      patients who underwent isolated ACL replacement and whose rehabilitation protocol
      included early motion. Group B consisted of 20 patients who underwent combined
      arthroscopic meniscal repair and ACL replacement. Partial weight bearing and
      restriction of range of motion for 6 weeks was recommended for these patients.
      The only 2 variables between the groups were the meniscal repair and the
      postoperative rehabilitation. Patients were evaluated clinically and
      radiographically at 3, 6, and 12 months postoperatively. After correction for
      radiographic magnification, the tibial tunnel was measured at distal (T1), middle
      (T2), and proximal (T3) locations on both anteroposterior and lateral views.
      RESULTS: At 1-year follow-up evaluations, tunnel enlargement was significantly
      higher in the group with early motion, in both the anteroposterior and lateral
      views, in all but one location (anteroposterior, T1). The enlargement was greater
      in the mid-portion (T2) of the tunnel in both groups. The mean percentage was
      45.92% for group A and 23.34% for group B ( P <.05) in the anteroposterior view,
      and 48.14% for group A and 24.47% for group B ( P <.05) in the lateral view. No
      correlation was found between tunnel enlargement and clinical results or between
      tunnel enlargement and joint laxity measured by a KT-1000 arthrometer.
      CONCLUSIONS: Our study confirms that early motion increases the amount of tibial
      tunnel enlargement after anterior cruciate ligament replacement with hamstring
      autograft. This may have an impact on future rehabilitation protocols. LEVEL OF
      EVIDENCE: Level II.

PMID- 15241307
TI  - Comparison of partial meniscectomy versus meniscus repair for bucket-handle
      lateral meniscus tears in anterior cruciate ligament reconstructed knees.
AB  - PURPOSE: For patients who underwent anterior cruciate ligament (ACL)
      reconstruction and had an unstable bucket-handle tear and no other meniscus
      lesions or articular damage, we sought to determine if repair of the lateral
      meniscus was superior to partial meniscectomy with regard to subjective and
      objective results. TYPE OF STUDY: Retrospective cohort study. METHODS: Between
      1982 and 1995, 91 patients met the inclusion criteria of having an ACL tear and
      an isolated unstable, bucket-handle meniscus tear. Patients were excluded if they
      had medial meniscus tears or chondral lesions. All patients underwent ACL
      reconstruction using patellar tendon autografts. Sixty-seven lateral menisci
      underwent repair using an inside-outside technique, while 24 lateral menisci were
      partially excised. Subjective follow-up evaluation was obtained with a modified
      Noyes questionnaire. Patients were objectively evaluated according to
      International Knee Documentation Committee (IKDC) knee evaluation criteria.
      RESULTS: The mean subjective total score for the repair group was 92.5 +/- 9.4
      (mean time, 7.0 +/- 2.6 years postoperatively), and the mean score for the
      removal group was 88.7 +/- 13.2 (mean time 11.1 +/- 4.0 years; P =.2014). The
      mean pain scores were 16.8 +/- 3.1 points for the repair group and 14.0 +/- 4.0
      for the partial excision group, which was statistically significant (P =.0478).
      The distribution of IKDC overall grades was not statistically significantly
      different between groups (P =.0947). Two of 67 meniscus repairs failed, requiring
      subsequent removal. CONCLUSIONS: Results showed that patients in the partial
      meniscectomy group had more pain than in the repair group, but no statistically
      significant difference was found between groups for overall subjective score or
      IKDC grade. Further follow-up evaluation is needed before definitive treatment
      can be recommended. LEVEL OF EVIDENCE: Level III.

PMID- 15241308
TI  - Results of meniscal repair using a bioabsorbable screw.
AB  - PURPOSE: With most all-inside arthroscopic meniscal repair devices, the surgeon
      has no need for additional incisions or arthroscopic knot tying, and surgical
      time is decreased compared with traditional suture repair. Although previous
      studies have examined the pullout strength of various all-inside devices,
      clinical data is lacking and has been presented for only a few implants. This
      study evaluates the clinical results of meniscal repair using a bioabsorbable
      screw. TYPE OF STUDY: Retrospective case series. METHODS: Twenty-five patients
      underwent 26 all-inside meniscal repairs using this device. Patient interviews
      were performed as was retrospective evaluation of patient records. Complications
      and repeat surgeries were noted. RESULTS: The average age of the patients was
      28.8 years (range, 15 to 44). The surgeries included 19 medial meniscus repairs
      and 7 lateral meniscus repairs; 12 patients underwent concomitant anterior
      cruciate ligament (ACL) reconstruction. We found 11 isolated meniscal repairs in
      stable knees and 2 isolated meniscal repairs in ACL-deficient knees. An average
      of 3.6 screws (range, 1 to 6) were used during the meniscal repairs. Eighteen of
      25 patients were contacted at an average of 106 weeks (range, 70 to 189)
      postoperatively. The mean Tegner score was 5, and the mean modified Lysholm score
      was 84. Three repeat surgeries were performed for failure of meniscal healing,
      and one repeat surgery was performed for migration of an implant. An additional
      patient who underwent medial meniscal repair noted a painless mild prominence on
      the medial aspect of the knee approximately 8 weeks after surgery. This
      prominence resolved completely over 6 months and did not require a second
      surgery. CONCLUSIONS: The bioabsorbable screw appears to be a safe and effective
      device for meniscal repair. Rare complications occurred that involved implant
      migration and transient inflammatory responses. Clinical success appears
      comparable to reported results with other methods of meniscal repair. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 15241309
TI  - Surgery about the coracoid: neurovascular structures at risk.
AB  - PURPOSE: The purpose of this study was to examine the neurovascular structures at
      risk when performing surgery about the coracoid. TYPE OF STUDY: Anatomic
      cadaveric study. METHODS: Five fresh-frozen cadaveric shoulders were dissected to
      determine the dimensions of the coracoid and the distance from the coracoid to
      adjacent neurologic and vascular structures. The minimal distance from the
      coracoid tip to the axillary nerve, musculocutaneous nerve, the lateral cord of
      the brachial plexus, and the axillary artery was measured using a precision
      caliper. Similarly, the minimal distance from the base of the coracoid to the
      axillary nerve, musculocutaneous nerve, the lateral cord of the brachial plexus,
      and the axillary artery was measured. RESULTS: The coracoid tip was defined as
      that portion of the bone that was distal to the "elbow" of the coracoid. Results
      showed that the mean width (medial-to-lateral dimension in the plane of the
      subscapularis tendon) of the coracoid tip was 15.9 +/- 2.2 mm, and the mean
      length of the coracoid tip was 22.7 +/- 4.5 mm. The mean thickness of the
      coracoid tip at its midportion was 10.4 +/- 1.5 mm. The portion of the coracoid
      tip which was closest to the neurovascular structures was the anteromedial
      portion of the coracoid tip. The distance from the anteromedial portion of the
      coracoid tip to the axillary nerve, the musculocutaneous nerve, the lateral cord,
      and the axillary artery was 30.3 +/- 3.9 mm, 33.0 +/- 6.2 mm, 28.5 +/- 4.4 mm,
      and 36.8 +/- 6.1 mm, respectively. Similarly, the portion of the base of the
      coracoid that was closest to the neurovascular structures was its anteromedial
      portion. The shortest distance from the anteromedial aspect of the base of the
      coracoid to the axillary nerve, the musculocutaneous nerve, the lateral cord, and
      the axillary artery was 29.3 +/- 5.6 mm, 36.5 +/- 6.1 mm, 36.6 +/- 6.2 mm, and
      42.7 +/- 7.3 mm, respectively. CONCLUSIONS: Procedures about the coracoid are
      relatively safe procedures. The lateral cord of the brachial plexus is at
      greatest risk during dissection about the tip of the coracoid, and the axillary
      nerve is at greatest risk during dissection about the base of the coracoid. The
      safety of arthroscopic coracoplasty or interval releases is further increased by
      the fact that most of the work is performed on the lateral aspect of the
      coracoid, which is even further away from the neurovascular structures. CLINICAL
      RELEVANCE: This study quantifies the relative risk of injury to neurovascular
      structures during arthroscopic surgery about the coracoid.

PMID- 15241310
TI  - Glenohumeral arthroscopy portals established using an outside-in technique:
      neurovascular anatomy at risk.
AB  - PURPOSE: The purpose of this study was to examine the neurovascular structures at
      risk during placement of glenohumeral arthroscopy portals using an outside-in
      technique. TYPE OF STUDY: Anatomic cadaveric study. METHODS: Five fresh-frozen
      cadaveric specimens were used in this study. Each shoulder was mounted on a
      custom-designed apparatus allowing shoulder arthroscopy in a lateral decubitus
      position. The following portals were established using an outside-in technique
      and marked using an 18-gauge spinal needle: posterior, posterolateral, anterior,
      5-o'clock, anterosuperolateral, and Port of Wilmington. Each specimen was
      carefully dissected after the procedure, and the distance from each portal site
      to the adjacent relevant neurovascular structures (axillary nerve,
      musculocutaneous nerve, lateral cord of the brachial plexus, cephalic vein, and
      axillary artery) was measured using a precision caliper. RESULTS: Except for the
      cephalic vein, all of the neurovascular structures were more than 20 mm away from
      all the portals evaluated. When creating either an anterior portal or a 5-o'clock
      position portal, the mean distance from the portal to the cephalic vein was 18.8
      mm and 9.8 mm, respectively. In one anterior portal, a direct injury to the
      cephalic vein occurred. CONCLUSIONS: Our study suggests that shoulder arthroscopy
      portals placed in an outside-in fashion are unlikely to produce neurologic
      injury. However, the cephalic vein is at risk during placement of an anterior or
      5-o'clock position portal, although probably with minimal subsequent patient
      morbidity. Placing portals in an outside-in fashion guarantees the correct angle
      of approach, with minimal risk to adjacent neurologic structures. CLINICAL
      RELEVANCE: This study shows the safety of standard and accessory glenohumeral
      arthroscopy portals.

PMID- 15241311
TI  - Thermal profile of radiofrequency energy in the inferior glenohumeral ligament.
AB  - PURPOSE: Currently, two different methods of applying radiofrequency (RF) energy
      (monopolar and bipolar) are available to the surgeon for thermal shortening of
      the shoulder capsule. The objective of this study was to investigate the
      temperature changes and the thermal conduction across the human inferior
      glenohumeral ligament (IGHL) during radiofrequency energy application. METHODS:
      Thermistors were secured onto both the intra-articular and extra-articular
      surfaces of human IGHL. Monopolar RF energy and bipolar RF energy were delivered
      to the intra-articular surface at the manufacturer's recommended settings. Pre
      treatment and post-treatment ligament lengths, widths, heating times, and
      temperatures were measured and compared. RESULTS: For the monopolar devices,
      temperature spikes to 89 degrees C were recorded for the set temperature of 67
      degrees C, averaging 77 degrees C +/- 10 degrees C. Temperatures across the
      ligament averaged 48 degrees C +/- 3 degrees C. For both devices, the IGHL became
      thicker with higher RF settings. Recorded temperatures decreased as distance
      increased from the point of application. Maximum temperatures occurred at least 6
      to 7 seconds after cessation of energy application. CONCLUSIONS: The bipolar and
      monopolar devices had similar conduction times across the ligament, suggesting
      that this occurs by simple diffusion of heat. Bipolar and monopolar devices were
      equally efficacious for capsular shrinkage if the extent of the shortening is
      tightly defined. CLINICAL RELEVANCE: The thermal probe should not rest in one
      position for an extended period of time during RF energy application because, as
      our study showed, the monitoring of temperature or the visualization of tissue
      change is not efficacious for determining the end point of thermal shrinkage of
      the shoulder capsule.

PMID- 15241312
TI  - Glenoid suture anchor fixation strength: Effect of insertion angle.
AB  - PURPOSE: The purpose of this study was to determine the effect of varying
      insertion angles on the fixation strength of screw-in devices placed in the
      glenoid rim. Type of study Cadaveric biomechanical analysis. METHODS: Eighteen
      cadaveric glenoids had 3.0-mm cannulated screws inserted for a depth of 10 mm in
      all 4 quadrants: anterior superior (AS), anterior inferior (AI), posterior
      superior (PS), posterior inferior (PI). Screws were inserted along the orthogonal
      to the glenoid rim at the point of insertion or at angles that deviated from this
      vector by 20 degrees and 40 degrees. Load to failure was performed at 10 mm/s
      along the orthogonal to the point of insertion. RESULTS: For screws inserted
      orthogonal to the glenoid rim, the average load to failure was highest for the PS
      quadrant (733 +/- 369 N) and lowest for the AI quadrant (272 +/- 69 N). The AS
      and PI quadrants showed intermediate values (549 +/- 334 N and 484 +/- 141 N,
      respectively). Deviation from orthogonal correlated with decreased fixation
      strength. This decrease was statistically significant in the AS and PI quadrants,
      with deviation of 40 degrees, and in the AI quadrant, with deviation of 20
      degrees, as well as 40 degrees. Conclusions Insertion angles for screw-in
      fixation devices should be orthogonal to the glenoid rim at the point of
      insertion to maximize strength. Deviation of 40 degrees from orthogonal
      compromises fixation in most quadrants and deviation as little as 20 degrees can
      compromise fixation in the AI quadrant. CLINICAL RELEVANCE: To maximize strength
      of labral reattachment to the bony glenoid, screw-in type fixation devices should
      be inserted as orthogonal to the glenoid rim as possible. This is especially true
      for Bankart repairs, because device pullout occurs at significantly lower loads
      in the anteroinferior quadrant compared with the other 3 quadrants. Deviating as
      little as 20 degrees further decreases fixation strength significantly.

PMID- 15241313
TI  - Relation between adhesive capsulitis and acromial morphology.
AB  - PURPOSE: The purpose of this study was to determine whether a relationship
      existed between primary adhesive capsulitis and acromial morphology. TYPE OF
      STUDY: Case control series. METHODS: Between January 1999 and June 2002, a total
      of 100 patients (104 shoulders) were diagnosed with adhesive capsulitis. A
      retrospective chart review was performed of all of these patients. A total of 67
      patients (69 shoulders) met the inclusion criteria of primary adhesive
      capsulitis. The patients' range of motion and signs of impingement were
      documented. The supraspinatus outlet radiographs were assessed, and each
      patient's acromial morphology was graded as type I, II, or III. A case control
      group of 53 patients (58 shoulders) was assessed to determine the validity of our
      results. This group consisted of a series of new patients that were referred to
      the clinic during February 2003 for assessment of their shoulders. RESULTS: The
      average age of the patients in the adhesive capsulitis group was 52.5 +/- 7.6
      years, with 34 women (50.7%) and 33 men (49.3%). The control group had an average
      age of 51.1 +/- 16.9 years in a series of 19 (35.8%) women and 34 (64.2%) men.
      The average range of motion was 98.0 degrees +/- 23.5 degrees of forward
      elevation, and 91.9 degrees +/- 24.3 degrees of abduction. The forward elevation
      was 165.5 degrees +/- 15.3 degrees and the abduction was 162.4 degrees +/- 18.4
      degrees. The predominant acromial morphology in both groups in this study was a
      type II acromion (75.4% in the adhesive capsulitis group and 74.1% in the control
      group). The chi-square analysis within the specific groups showed statistically
      significant differences in the number of type II compared with type I acromions,
      and type II compared with type III acromions in both series. However, statistical
      analysis showed no significant difference between the various acromial types when
      comparing the adhesive capsulitis group with the control group. CONCLUSIONS: Our
      results show a significant number of patients with both adhesive capsulitis and,
      in the control group, type II acromions. We found no statistical difference
      between these 2 groups. Based on our results, the intrinsic trauma that occurs
      from subacromial space narrowing caused by the anterior acromial shape, cannot be
      implicated as the cause of primary adhesive capsulitis. LEVEL OF EVIDENCE: Level
      III, case control study.

PMID- 15241314
TI  - Arthroscopically assisted rotator cuff repair.
AB  - PURPOSE: The purpose of this study is to analyze the technique and value of
      arthroscopically assisted rotator cuff repair based on follow-up results after 3
      years. TYPE OF STUDY: Case series. METHODS: Since the beginning of 1997, 216
      patients included in a clinical case series at the Department of Trauma Surgery
      of the Hospital of the Barmherzigen Bruder Eisenstadt have undergone
      arthroscopically assisted rotator cuff repair. Radiographic, clinical, and
      intraoperative parameters were carefully documented. All patients were treated
      with an arthroscopically assisted transosseous technique, in which bone tunnels
      are drilled with a target drill unit through the humeral head lateral to the
      biceps tendon from a third ventrocaudal incision on the humerus. The
      nonresorbable sutures placed into the cuff with a suture punch are passed
      transosseously and tied in the incision directly on the humeral head using a knot
      pusher. In December 2000, 84 patients (average age, 54.8 years; range, 28 to 74
      years) underwent a clinical follow-up evaluation after a mean follow-up time of
      35 months (28 to 44 months). RESULTS: The average Constant score improved from a
      preoperative rating of 44.9 to a postoperative rating of 87.2. University of
      California, Los Angeles score was improved from 11.3 to 31.1 ( P <.001). Time of
      preoperative history, tear size, and condition of the long biceps tendon were
      found to have significant influence on results (P <.05). Thus, 20 patients with
      chronic, untreated tears of the long biceps tendon showed significantly worse
      results with a score of 81.8. Patients with curved or hooked acromion types
      (Bigliani II and III) showed significantly better results (P <.05) and patients
      with extensive tears had significantly worse results because of a residual
      strength deficit. The essential determinant was achievement of a stable tear
      closure with arthroscopic verification and documentation. Thus, 8 patients with a
      documented small gap between repaired cuff and bone showed a significantly worse
      rating in the Constant score, with 80.5 (P <.05). The complications encountered
      included development of seroma in one case and one case with frozen shoulder
      symptoms. CONCLUSIONS: Arthroscopically assisted repair of the rotator cuff was
      shown to be an effective procedure, guaranteeing good clinical results for medium
      and large-sized tears with adequate mobility. Advantages include a primary
      stability comparable to that seen with open repair. Minimized trauma to soft
      tissue is associated with a lesser degree of postoperative pain and scarring and
      reduced hospitalization. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 15241315
TI  - Arthroscopically assisted treatment of ankle fractures: arthroscopic findings and
      surgical outcomes.
AB  - PURPOSE: Malleolar fractures have been reported to be associated with a poor
      prognosis even when the anatomic reduction is complete. Soft tissue injuries such
      as damage to the cartilage and ligaments, soft tissue impingement, and the
      existence of free bodies within the intra-articular space account for this poor
      outcome. In treating fresh malleolar fractures, an arthroscope is used at our
      institution to confirm anatomic reduction on the articular surface and treat
      intra-articular injuries. This study evaluated the arthroscopic findings and
      surgical outcome for fresh malleolar fractures. TYPE OF STUDY: Prospective case
      study. METHODS: The subjects were 105 patients (105 joints) who had experienced
      malleolar fractures and had undergone surgical fixation between January 1996 and
      May 1999. Arthroscopy was used to confirm the fracture line, cartilaginous
      damage, presence of detached cartilaginous fragments in the articular space,
      ligament damage, and diastasis of the distal tibiofibular joint. The
      cartilaginous damage was treated using shaving, and the free cartilaginous
      fragments were excised. Diastasis of the distal tibiofibular joint was treated
      using distal tibiofibular joint fixation, using a screw. Fracture fixation was
      conducted after anatomic reduction had been confirmed using fluoroscopy and
      arthroscopy. RESULTS: Cartilaginous damage was noted in 21 patients, among whom
      13 were treated by shaving and 8 underwent cartilaginous fragment removal.
      Fixation of the distal tibiofibular joint was conducted in 8 patients. From a
      postoperative radiographic evaluation, a good result in 100 cases and a fair
      outcome in 5 were confirmed. The clinical results were good in all, and no
      postoperative complications or pseudoarthrosis were noted. CONCLUSIONS: The use
      of an arthroscope during treatment of malleolar fractures enables diagnosis and
      treatment of the lesions within the ankle joint, producing a satisfactory
      surgical outcome. LEVEL OF EVIDENCE: Level IV, therapeutic study, case series (no
      control group).

PMID- 15241316
TI  - Osteonecrosis after arthroscopic meniscectomy using radiofrequency.
AB  - The purpose of this report is to describe a case of osteonecrosis that occurred
      after arthroscopic meniscectomy associated with a radiofrequency device. The
      patient developed increasing knee pain and disability 6 months after arthroscopic
      meniscectomy. Magnetic resonance imaging showed subchondral osteonecrosis of both
      femoral condyles with cyst formation.

PMID- 15241317
TI  - Deltoid (triangular)-shaped anterior cruciate ligament that caused notch
      impingement: a report of two cases.
AB  - In this article, we present 2 previously unreported cases of anterior cruciate
      ligaments (ACL) that had a wide deltoid (triangular)-shaped tibial insertion in
      the coronal plane that caused impingement at the intercondylar notch, inferior
      parts of patellofemoral sulcus, and the posterior cruciate ligament (PCL).
      Ligamentoplasty was used in both cases. Inferomedial and inferolateral parts of
      the ACL that caused impingement were excised, and the normal width of the tibial
      insertion of the ACL was provided.

PMID- 15241318
TI  - Dropping of an EndoButton into the knee joint 2 years after anterior cruciate
      ligament repair using proximal fixation methods.
AB  - One of the most discussed subjects regarding anterior cruciate ligament (ACL)
      repair methods is femoral fixation. One of the materials often used for fixation
      in recent years is the EndoButton (Acufex Microsurgical, Mansfield, MA), which
      provides rapid and secure fixation. Although many reports about femoral fixation
      with EndoButton have been published, insufficient information is available on
      possible complications. We have used 240 EndoButtons in our clinic for ACL
      repairs since 1997. The goal of this study was to report a case of ACL repair
      with an EndoButton, in which we experienced a complication. In this case, the
      EndoButton dropped into the knee joint after 2 years.

PMID- 15241319
TI  - Subchondral giant-cell tumor of the proximal tibia: arthroscopic treatment for
      accelerated articular cartilage and meniscal degeneration in two patients.
AB  - Giant-cell tumor most commonly occurs in the distal femur and proximal tibia and
      characteristically involves the subchondral bone. Incomplete resection leads to
      recurrence rates of up to 50%. Intralesional curettage, adjuvant treatments, and
      polymethyl methacralate (PMMA) reconstruction is the current mainstay of
      treatment and has produced recurrence rates of less than 10%. Achieving adequate
      curettage while preserving the articular cartilage of the tibial plateau poses a
      significant challenge, especially when the tumor involves the subchondral bone.
      We report on 2 cases, both with symptomatic full-thickness tibial articular
      cartilage loss and one with a meniscal tear, after curettage, phenol cautery, and
      PMMA reconstruction of giant-cell tumor of the proximal tibia. Arthroscopic
      chondroplasty and planing of the exposed cement was performed in both cases,
      theoretically reducing focal areas of stress concentration that could lead to
      further meniscal damage and injury to the femoral condyle articular surface in
      weight-bearing. Partial meniscectomy for a complex meniscal tear was performed in
      one case. Eighteen months postoperatively, both patients were asymptomatic,
      working full-time, and participating in light physical activity. Repetitive heavy
      loading of the knee, such as running, was prohibited, and long-term follow-up is
      warranted to assess for further joint degeneration and need for total knee
      arthroplasty.

PMID- 15241320
TI  - A case of intra-articular snapping hip caused by articular cartilage detachment
      from the deformed femoral head consequent to Perthes disease.
AB  - We treated a relatively rare case of intra-articular snapping hip caused by an
      articular cartilage fragment detached from the deformed femoral head consequent
      to Perthes disease. We report the pathology as well as diagnosis and treatment of
      this case. A 24-year-old man presented with right coxalgia. He was diagnosed with
      Perthes disease at a young age and was treated conservatively. Six months before
      the patient visited our department, he started having intense pain accompanied by
      a clicking sound when he extended and at the same time externally rotated the
      right hip joint from a flexed position. Although a radiogram showed Stulberg
      class 3 deformity of the femoral head, the joint space was well preserved and no
      bone cyst or bone spur formation was seen. Computed tomography (CT) and magnetic
      resonance imaging (MRI) showed no abnormal findings inside the femoral head and
      in the hip joint. However, when 5 mL of 2% lidocaine hydrochloride was injected
      into the hip joint, the snapping phenomenon persisted but the sharp pain was
      temporarily resolved. Arthroscopic finding showed a valve-shaped detachment of
      articular cartilage in the anteromedial side of the femoral head. Arthroscopic
      shaving of the detached fragment was conducted. The pain and clicking sound
      accompanying hip joint movement disappeared postoperatively. Hip joint
      arthroscopy is useful for the diagnosis and treatment of intra-articular type
      snapping hip when the cause of snapping is inside the joint cavity.

PMID- 15241321
TI  - Arthroscopic outside-in meniscal repair through a needle hole.
AB  - This article describes an alternative method for outside-in repair of a
      longitudinal meniscal tear through a needle hole, which will produce an almost
      negligible cutaneous scar. The procedure is performed under arthroscopic set-up
      using an 18-gauge needle preloaded with appropriate suture material. Insert the
      needle twice through the same cutaneous entry hole to form a mattress loop across
      the torn meniscal segments. The first insertion penetrates both segments and
      forms a loop. The second insertion then engages the outer segment and forms
      another loop. Draw the free end of this second loop into the joint and feed it
      into the first loop. Pull the first loop out from the joint together with the
      trapped portion near the free end, until the whole suture becomes a vertical
      mattress. Finally, tie a slipknot and several half hitches to close the meniscal
      gap under the stitch. In a large bucket-handle tear, stitches should be started
      at the middle and then alternating anteriorly and posteriorly 3 to 4 mm apart. To
      ensure that no significant extracapsular structures are trapped in each stitch, a
      13-gauge needle can be used as a cannula sheath. This technique is economical and
      technically safe and simple for reparable meniscal lesions, including the
      posterior horn.

PMID- 15241322
TI  - Endopearl augmentation of bioabsorbable interference screw fixation of a soft
      tissue tendon graft in a tibial tunnel.
AB  - In this technical note, we introduce a new technique for tibial side soft tissue
      graft fixation using a bioabsorbable interference screw augmented with an
      EndoPearl (Linvatec, Largo, FL) for ACL reconstruction. This technique will
      enable the knee surgeon to use shorter grafts while minimizing slippage without
      reducing fixation strength.

PMID- 15241323
TI  - Arthroscopic treatment of acute acromioclavicular joint dislocation.
AB  - An original technique for the treatment of acute acromioclavicular (AC) joint
      dislocations is proposed. It consists of a closed reduction and stabilization of
      the AC joint, positioning a cannulated screw between the clavicle and the
      coracoid under arthroscopic control, without any exposure to x-rays. The conoid
      and trapezoid ligaments are not sutured or reconstructed. The screw is finally
      removed under local anesthesia 12 weeks after surgery. The described procedure
      has been performed in 9 patients. Short-term preliminary results show an
      excellent functional outcome without any residual pain. Among the advantages of
      the technique are that it does not require specific instrumentation, is a
      minimally invasive approach, has the possibility of searching the glenohumeral
      joint for associated lesions and eventually treating them, and has the benefits
      of not exposing the patient or surgical team to ionizing radiation.

PMID- 15241324
TI  - An arthroscopic stitch for massive rotator cuff tears: the Mac stitch.
AB  - Arthroscopic repair of rotator cuff tears has become popular with the advancement
      in technology and arthroscopic technique. As we attempt to arthroscopically
      repair larger rotator cuff tears, we are relying more on tissue fixation. The
      tendon-suture interface has been recognized as the weak link in rotator cuff
      repair. In this article, we propose the use of the Mac stitch--a simple
      modification of suture placement, a combination of a horizontal and vertical loop
      at the site of repair--to increase the strength of tissue fixation. The Mac
      stitch is a simple arthroscopic stitch that can be used for small and massive
      rotator cuff repairs.

PMID- 15241328
TI  - Arthroscopic treatment for greater tuberosity fractures: rationale and surgical
      technique.
AB  - A description of a new technique for arthroscopic treatment of minimally
      displaced greater tuberosity fractures of the humerus and associated soft tissue
      lesions is presented. This kind of fracture is usually treated nonsurgically.
      However, recent evidence suggests that even a small amount of superior
      displacement may produce shoulder dysfunction and require a perfect surgical
      reduction and fixation. Moreover, any displaced fracture of the greater
      tuberosity presents a high rate of associated and largely undetected soft tissue
      lesions. To avoid underestimating accompanying soft tissue pathology,
      arthroscopic assessment before open treatment of greater tuberosity fractures has
      been suggested. In 2 earlier case reports, we described the use of an arthroscope
      not only to diagnose and treat a rotator cuff tear and a Bankart lesion
      associated with a minimally displaced greater tuberosity fracture but also to
      arthroscopically reduce and treat the fracture. With advancements in arthroscopy
      and equipment, we refined and systematized the original arthroscopic technique
      that we have routinely used since 1997. This article presents the new technique.

PMID- 15241329
TI  - Top tips for RIGIDfix femoral fixation.
AB  - The use of pin fixation for grafts in the femoral tunnel in anterior cruciate
      ligament (ACL) reconstruction is becoming more popular. The transtibial stiff
      femoral guides are necessary to ensure that the pins fix the graft. However, the
      cross pins can sometimes miss the femoral tunnel. As a result of some technical
      problems that we encountered, we introduced an extra step in the technique of the
      Mitek RIGIDfix ACL Graft Fixation System (Mitek Products, Ethicon, Edinburgh,
      UK). This article suggests some tips for fixing problems that arise in cases in
      which the graft is accidentally missed with the cross pins.

PMID- 15241330
TI  - Pseudoaneurysm of the anterior tibial artery after ankle arthroscopy.
AB  - Ankle arthroscopy is believed to have the least vascular complications compared
      with other types of arthroscopies. We present a case of traumatic pseudoaneurysm
      of the anterior tibial artery after ankle arthroscopy, an extremely rare
      complication that was treated surgically and had an uneventful recovery.

PMID- 15241337
TI  - Diagnosis and classification of mast cell proliferative disorders: delineation
      from immunologic diseases and non-mast cell hematopoietic neoplasms.
AB  - In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the
      release of chemical mediators from MCs, the pathologic infiltration of neoplastic
      MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC
      infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis
      might regress spontaneously. Systemic mastocytosis (SM) is more frequently
      diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived
      myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the
      majority of such patients. The natural clinical course in SM is variable. Whereas
      most patients remain at the indolent stage for many years, some have aggressive
      SM (ASM) at diagnosis. Other patients have an associated clonal hematologic non
      MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant
      characterized by circulating MCs and fatal disease progression. The diagnoses of
      ASM, SM-AHNMD, and MCL might be confused with a variety of endocrinologic,
      vascular, or immunologic disorders. It is therefore of particular importance to
      be aware of the possibility of an underlying (malignant) MC disease in patients
      with unexplained vascular instability, unexplained (anaphylactoid) shock,
      idiopathic flushing, diarrhea, headache, and other symptoms that might be
      mediator related. An important diagnostic clue in such cases is an increased
      serum tryptase level. The current review provides an overview of mastocytosis and
      its subvariants and a practical guide that might help to delineate mastocytosis
      from unrelated systemic disorders.

PMID- 15241338
TI  - The biology of Kit in disease and the application of pharmacogenetics.
AB  - C-kit encodes a transmembrane protein with intrinsic tyrosine kinase activity,
      which functions as the receptor for stem cell factor. It is expressed on a
      variety of cell types, including mast cells, hematopoietic progenitor cells,
      melanocytes, germ cells, and gastrointestinal pacemaker cells. Mutations
      resulting in alteration of Kit function are associated with diseases involving
      each of these cells. Recent development of tyrosine kinase inhibitors led to
      their evaluation as novel therapies for diseases associated with Kit activation.
      This review will discuss the pathobiology of Kit in human disease, with a
      particular emphasis on implications for potential targeted treatment strategies
      in mast cell disease.

PMID- 15241339
TI  - Mast cells in innate immunity.
AB  - Mast cells have been most extensively studied in their traditional role as an
      early effector cell of allergic disease. However, in the majority of individuals,
      it might be the role of this cell as a sentinel in host defense that is most
      important. Mast cells have been repeatedly demonstrated to play a critical role
      in defense against bacterial infections, and evidence for their involvement in
      early responses to viral and fungal pathogens is growing. Mast cells are
      activated during innate immune responses by multiple mechanisms, including well
      established responses to complement components. In addition, novel mechanisms
      have emerged as a result of the explosion of knowledge in our understanding of
      pattern-recognition receptors. The mast cell shares many features with other
      innate immune effector cells, such as neutrophils and macrophages. However, a
      unique role for mast cells is defined not only by their extensive mediator
      profile but also by their ability to interact with the vasculature, to expedite
      selective cell recruitment, and to set the stage for an appropriate acquired
      response.

PMID- 15241340
TI  - Systemic mastocytosis associated with acute myeloid leukemia: case report and
      implications for disease pathogenesis.
AB  - Mastocytosis may be associated with clonal nonmast cell lineage hematologic
      diseases, including myelodysplastic syndromes, myeloproliferative disorders, and
      acute myeloid leukemia. Here we present a patient with the simultaneous diagnosis
      of mastocytosis and an acute myeloid leukemia, M2 subtype in the French-American
      British classification, with t(8;21) carrying a population of immature mast cell
      precursors, and discuss this presentation in the context of a potential
      pathogenetic cellular link between this leukemia and mastocytosis.

PMID- 15241341
TI  - Mast cell mediator release in nonasthmatic subjects after endobronchial adenosine
      challenge.
AB  - BACKGROUND: Adenosine 5'-monophosphate (AMP) has been shown to cause
      bronchoconstriction in atopic subjects but to have no effect on nonatopic
      nonasthmatic subjects. Endobronchial AMP challenge has previously been shown to
      cause mast cell mediator release in asthmatic subjects, but it is unknown whether
      a similar response occurs in atopic nonasthmatic and nonatopic nonasthmatic
      control subjects who have no response to inhalation AMP challenge. OBJECTIVE:
      This study examined the change in mast cell-derived products after endobronchial
      saline challenge and AMP challenge in subjects with and without a positive
      inhalation response to AMP. METHODS: Inhalation challenge with AMP challenge was
      performed in normal, atopic nonasthmatic, and atopic asthmatic subjects. Levels
      of mast cell mediators were measured after endobronchial adenosine challenge and
      after placebo endobronchial saline challenge. RESULTS: There were significant
      increases in histamine, tryptase, protein, and prostaglandin D2 levels (P=.02,
      P=.02, P=.01, and P=.01, respectively) after AMP challenge compared with after
      saline challenge in nonatopic nonasthmatic subjects. There was no significant
      increase in any mediator in either of the other 2 groups. CONCLUSION: This study
      suggests dissociation between mediator release and bronchoconstriction in
      response to AMP.

PMID- 15241342
TI  - Worldwide severity and control of asthma in children and adults: the global
      asthma insights and reality surveys.
AB  - BACKGROUND: In 1995, the Global Initiative for Asthma (GINA) guidelines
      recommended goals for the management of asthma, which were updated in 2002.
      However, there are no recent international surveys on the real management of
      asthma. OBJECTIVE: The Asthma Insights and Reality surveys are the first large
      scale surveys aimed at determining international variations in the severity,
      control, and management of asthma in children and adults. METHODS: A cross
      section of households in 29 countries in North America, Europe, and Asia were
      surveyed to identify from the general population asthmatic patients with symptoms
      within the last year or who were taking current asthma medication. A standard
      questionnaire was administered to 7786 adults, and, through a proxy, to 3153
      children with asthma. Objective and subjective patient perception of asthma
      control and severity were assessed, including access to medical care, health care
      use, missed work-school, and medication use. RESULTS: Despite variations at a
      country level, a substantial effect of asthma on patients' lives was observed,
      with considerable loss of schooldays and workdays. The current level of asthma
      control worldwide falls far short of the goals for long-term management in
      international guidelines. A significant proportion of patients continue to have
      symptoms and lifestyle restrictions and to require emergency care. The proportion
      of adult asthmatic patients who were current smokers was also high. However, the
      use of anti-inflammatory preventative medication, even in patients with severe
      persistent asthma, was low, ranging from 26% in Western Europe to 9% in Japan, as
      was the use of objective lung function testing. The correlation between self
      perceived severity of asthma and objective assessment of severity on the basis of
      GINA criteria was consistently poor in all areas. CONCLUSION: We conclude that
      there is direct evidence for suboptimal asthma control in many patients
      worldwide, despite the availability of effective therapies, with long-term
      management falling far short of the goals set in the GINA guidelines.

PMID- 15241343
TI  - Effect of sex and haplotype on plasma tryptase levels in healthy adults.
AB  - BACKGROUND: The total level of alpha-tryptase and ss-tryptase in serum or plasma
      is used as a clinical indicator of the mast cell burden. OBJECTIVE: The effect of
      the tryptase haplotype and of sex on the total tryptase level of healthy
      individuals was determined. METHODS: A novel hot-stop PCR technique was used to
      determine the tryptase genotype, and a standard fluoroenzyme immunoassay was used
      to measure total plasma tryptase levels in 106 healthy subjects. Mx modeling and
      the QTL association routine of Mendel 5.0 were used to analyze the data. RESULTS:
      Tryptase haplotypes exhibit a 1 (betaalpha/betaalpha):2 (betabeta/betaalpha):1
      (betabeta/betabeta) distribution, monomorphic for ss at 1 position and allelic
      for ss and alpha at the other position. The betaalpha haplotype has a frequency
      of 0.49. The betaalpha haplotype increases total tryptase levels by 0.5 ng/mL
      from the overall mean, whereas female sex increases the level by 0.2 ng/mL from
      the mean. CONCLUSION: The tryptase haplotype and sex each have a statistically
      significant effect on the total plasma tryptase level of healthy subjects.

PMID- 15241344
TI  - The mastocyte: the "other" inflammatory cell in immunopathogenesis.

PMID- 15241345
TI  - The role of the mast cell in asthma: induction of airway hyperresponsiveness by
      interaction with smooth muscle?
AB  - In a recent study, the difference between asthma and eosinophilic bronchitis (a
      condition characterized by cough but not airway hyperresponsiveness or airflow
      obstruction) was infiltration of airway smooth muscle (ASM) by mast cells. Mast
      cells produce a variety of lipid mediators, chemokines, cytokines, and enzymes
      that may interact with ASM cells to cause hyperreactivity to constrictive stimuli
      and proliferation, and activated ASM can produce stem cell factor and other
      chemokines, cytokines, and growth factors that may act in recruitment,
      differentiation, and retention of mast cells. Mast cell infiltration of the
      airways in asthma is T-cell-dependent, and TH2 cytokines from T cells and other
      sources act in mast cell expansion from circulating and tissue precursors. The
      recent data on interactions of mast cells and ASM suggest that this could be an
      important contributor to airway hyperresponsiveness in asthma. Why this occurs in
      asthma and how it is sustained remain to be established.

PMID- 15241346
TI  - The K+ channel iKCA1 potentiates Ca2+ influx and degranulation in human lung mast
      cells.
AB  - BACKGROUND: Human lung and blood-derived mast cells express a Ca2+-activated K+
      channel (KCA) that has electrophysiological properties resembling the
      intermediate conductance KCA (iKCA1). This channel is predicted to enhance IgE
      dependent mast cell responses. OBJECTIVE: To confirm the identity of this channel
      as iKCA1 in human lung mast cells and to examine the effect of an iKCA1 opener, 1
      ethyl-2-benzimidazolinone (1-EBIO), on Ca2+ influx and degranulation after IgE
      dependent activation. METHODS: iKCA1 expression was examined by using RT-PCR. Ion
      currents were measured by using the patch clamp technique in human peripheral
      blood-derived mast cells, freshly isolated human lung mast cells (HLMCs), and
      long-term cultured HLMCs (LTHLMCs). Currents were manipulated with the specific
      iKCA1 opener 1-EBIO and the iKCA1 blockers clotrimazole and TRAM-34. Ratiometric
      Ca2+ imaging was performed on single fura-2-loaded cells, and histamine release
      was measured by radioenzymatic assay. RESULTS: Both fresh HLMCs and LTHLMCs
      expressed iKCA1 mRNA. The iKCA1 opener 1-EBIO induced iKCA1 currents in 89% of
      human peripheral blood-derived mast cells, 12% of fresh HLMCs, and 67% of
      LTHLMCs, which were blocked by the iKCA1 blockers clotrimazole and TRAM-34. After
      cell activation with a suboptimal concentration of anti-IgE, 1-EBIO enhanced the
      IgE-dependent rise in cytosolic-free Ca2+ and potentiated IgE-dependent histamine
      release. CONCLUSION: Opening of iKCA1 enhances IgE-dependent Ca2+ influx and
      histamine release in HLMCs. Inhibition of iKCA1 may provide a novel approach to
      the treatment of mast cell-mediated disease.

PMID- 15241347
TI  - Role for cysteinyl leukotrienes in allergen-induced change in circulating
      dendritic cell number in asthma.
AB  - BACKGROUND: Dendritic cells are important antigen-presenting cells. After an
      allergen inhalation, their numbers rapidly decrease in circulation and increase
      in the airway mucosa. OBJECTIVE: To investigate whether allergen-induced changes
      in the number of circulating dendritic cells are mediated by cysteinyl
      leukotrienes. METHODS: In a randomized, double-blind, crossover study, we
      examined the effects of 2 weeks of treatment with pranlukast (a cysteinyl
      leukotriene 1 [CysLT1] receptor antagonist) 300 mg twice daily and placebo on
      allergen-induced changes in airway responses and circulating dendritic cells in
      15 subjects with mild asthma. We examined by flow cytometry, before and at 3
      hours and 24 hours after allergen inhalation, the proportion of myeloid (CD33+)
      and plasmacytoid (CD123+) dendritic cells (HLA-DR+, CD14-, CD16-) among all
      peripheral blood mononuclear cells. The fraction of dendritic cells expressing
      CysLT1 receptor was also determined. RESULTS: Compared with placebo, pranlukast
      significantly attenuated both the maximum early (by 55%) and the late (by 39%)
      asthma responses, the allergen-induced methacholine airway hyperresponsiveness,
      and the increase in macrophage inflammatory protein 1alpha and 3alpha in induced
      sputum. A significantly greater proportion of CD33+ cells (55%) expressed CysLT1
      receptor compared with CD123+ cells (11%). Consistent with this, pranlukast
      prevented the allergen-induced decrease in CD33+ dendritic cells at 3 hours
      postallergen (mean Delta from baseline, +4.4%) compared with placebo (mean Delta,
      -8.4; P <.05), but not CD123+ cells. CONCLUSION: Pretreatment with pranlukast
      attenuated allergen-induced airway responses and the decrease in circulating
      myeloid dendritic cells, demonstrating a novel role of cysteinyl leukotrienes in
      dendritic cell trafficking.

PMID- 15241348
TI  - A comprehensive evaluation of IL4 variants in ethnically diverse populations:
      association of total serum IgE levels and asthma in white subjects.
AB  - BACKGROUND: The role of variation in the IL4 gene in asthma and allergy
      susceptibility is controversial. This cytokine is important in IgE isotype
      switching and the regulation of allergic inflammation; however, published studies
      have not delineated the specific role of variation in this gene in allergic
      disorders. OBJECTIVE: We sought to identify single nucleotide polymorphisms
      (SNPs) in IL4 and to evaluate the association of SNPs and haplotypes with asthma
      and allergic phenotypes (total serum IgE) in white, African American, and
      Hispanic asthmatic populations. METHODS: Sixteen individuals were resequenced,
      and 19 SNPs were identified; 2 novel and 17 SNPs were previously reported. Eleven
      of the SNPs were used to evaluate association in the 3 groups. RESULTS: Nine
      polymorphisms were associated with total serum IgE levels in white subjects
      (.0012 < or = P < or =.034), and 5 of these were also associated with asthma in
      this population (.010 < or = P < or =.031). Three common haplotypes were
      observed, and all were associated with either high or low serum IgE levels in
      white subjects (.00008 < or = P < or =.004). Inspection of the haplotypes
      revealed that 3017 G/T in intron 2 was the only SNP concordant with serum IgE
      levels (G allele with lower levels and T allele with higher levels). CONCLUSIONS:
      After a comprehensive genetic evaluation, our data suggest that the 3017 G/T
      variant or the haplotype it identifies influences IL4's ability to modulate total
      serum IgE levels. Inconsistencies with previously reported IL4 associations might
      be due to population differences in allele frequencies, the extent of linkage
      disequilibrium with this SNP or haplotype, or both.

PMID- 15241349
TI  - Dendritic cells modulated by cytokine-expressing adenoviruses alleviate
      eosinophilia and airway hyperresponsiveness in an animal model of asthma.
AB  - BACKGROUND: It has been found that TH1-related cytokines can decrease the
      accumulation of eosinophils in lung tissue and relieve airway constriction.
      OBJECTIVE: Dendritic cells (DCs) have been found to prime naive T-helper cells
      efficiently. In this study, DCs infected with TH1 cytokine-expressing adenovirus
      can be used to induce antigen-specific TH1 cells for treatment in an animal model
      of asthma. METHODS: Cytokine gene-modulated DCs pulsed with ovalbumin antigen
      (OVA) were injected intravenously into naive mice 1 week before sensitization
      with OVA antigen. The mice were then monitored for OVA-specific IgE, airway
      inflammatory cell infiltration, and airway hyperresponsiveness in the study.
      RESULTS: Significant levels of IL-12 or IL-18 were expressed by Ad-IL-12 or Ad-IL
      18 infected, bone marrow-derived DCs. Ad-IL-12 and Ad-IL-18 co-infected DCs
      effectively, decreasing sera anti-OVA IgE antibody levels, lung eosinophilia, and
      airway hyperresponsiveness. CONCLUSION: We concluded that DCs modulated by TH1
      prone cytokine-expressing adenoviruses can alleviate TH2-type airway inflammation
      in a murine model and can provide possible therapeutic application for DCs in
      asthma.

PMID- 15241350
TI  - Lung eosinophilic inflammation and airway hyperreactivity are enhanced by murine
      anaphylactic, but not nonanaphylactic, IgG1 antibodies.
AB  - BACKGROUND: Chronic airway inflammation is a fundamental feature of bronchial
      asthma, which is characterized by the accumulation and activation of inflammatory
      cells, such as mast cells and eosinophils, that are tightly regulated by TH2
      cytokines and chemokines. Recently, we demonstrated, in a murine model of asthma
      with immunosuppressed mice reconstituted with antigen-specific IgE or IgG1
      antibodies, that IgE, but not IgG1, participates in potentiation of airway
      inflammation and induction of airway hyperreactivity (AHR). The IgG1 antibody,
      however, did not elicit passive cutaneous anaphylactic reactions, which was in
      contrast to IgE. OBJECTIVES: Because 2 types of murine IgG1 have been
      demonstrated with regard to anaphylactic activity, the present experiments were
      undertaken to determine the role of anaphylactic and nonanaphylactic IgG1
      antibodies in the development of antigen-induced eosinophilia and AHR in this
      model. METHODS: Dinitrophenyl-conjugated, heat-coagulated hen's egg white was
      implanted in immunosuppressed mice reconstituted with anaphylactic or
      nonanaphylactic IgG1. Intratracheal challenge with aggregated dinitrophenyl
      ovalbumin was performed on day 14, and lung inflammatory and mechanical
      parameters were evaluated after 48 hours. RESULTS: Our results demonstrated that
      reconstitution of immunosuppressed mice with anaphylactic IgG1 antibodies in
      contrast to nonanaphylactic IgG1 antibodies potentiates their ability to have
      pulmonary eosinophilic inflammation and AHR. IL-5 and eotaxin levels in
      bronchoalveolar lavage fluid from anaphylactic IgG1-reconstituted mice were also
      higher than those in nonanaphylactic IgG1-reconstituted mice. CONCLUSIONS: These
      results indicate that the anaphylactic property of murine IgG1 molecules is
      essential for their capacity to enhance lung eosinophilic inflammation and to
      induce AHR.

PMID- 15241351
TI  - Family history, dust mite exposure in early childhood, and risk for pediatric
      atopy and asthma.
AB  - BACKGROUND: Dust mite allergen exposure is considered a major determinant of
      sensitization to these allergens during childhood and a risk factor for pediatric
      asthma. OBJECTIVE: By using a birth cohort in a setting with a substantial burden
      of dust mite allergen, we evaluated exposure and risk for outcomes related to
      allergy and asthma. METHODS: We collected dust from the bedrooms of 428 children
      born from 1987 to 1989 and measured Der f 1 and Der p 1 (microg/g dust,
      combined). Follow-up at 6 to 7 years of age included clinical examination, skin
      prick testing, specific serum IgE measurement, and methacholine challenge.
      RESULTS: No overall association was evident for any outcome except bronchial
      hyperresponsiveness (adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.00; P <.050;
      and OR, 0.53; CI, 0.27-1.04; P <.065 for dust mite allergen levels > or =2
      microg/g and >10 microg/g, respectively). With a parental history of allergy and
      asthma, there was an association between a positive dust mite skin test (OR,
      2.09; CI, 0.93-4.73; P <.076) and dust mite allergen level >10 microg/g. The
      inverse was true for children without a parental history. Dust mite exposure of
      >10 microg/g was associated with a decreased risk of current atopic asthma among
      children with a parental history (OR, 0.39; CI, 0.05-3.13; P <.376), but with
      increased risk if without a parental history (OR, 1.52; CI, 0.22-10.6; P <.673).
      CONCLUSION: Parental history is an important independent variable in the
      relationship between early dust mite exposure and atopic outcomes. Increased
      exposure during infancy is associated with a higher risk for sensitization in the
      presence of a positive parental history, but is protective among children of
      parents without a history of atopic disease.

PMID- 15241352
TI  - Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the
      National Survey of Lead and Allergens in Housing.
AB  - BACKGROUND: Exposures to dog and cat allergens are believed to play important
      roles in the etiology of asthma; however, the levels of these allergens have
      never been assessed in a representative sample of US homes. OBJECTIVE: The
      objective of this study was to estimate and characterize exposures to Can f 1
      (dog allergen) and Fel d 1 (cat allergen) in US homes. METHODS: Data were
      obtained from the National Survey of Lead and Allergens in Housing, a nationally
      representative survey of 831 US homes. Vacuumed-collected dust samples from the
      bed, bedroom floor, living room floor, and living room sofa were analyzed for
      concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust).
      RESULTS: Although a dog or cat had lived in only 49.1% of homes in the previous 6
      months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes,
      respectively. Averaged over the sampled sites, geometric mean concentrations
      (microg/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor
      dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and
      200 for Fel d 1. Among homes without the indoor pet, geometric mean
      concentrations were above 1.0. The independent predictors of elevated
      concentrations in homes without pets were all demographic variables that were
      also linked to a higher prevalence of pet ownership. CONCLUSIONS: Can f 1 and Fel
      d 1 are universally present in US homes. Levels that have been associated with an
      increased risk of allergic sensitization were found even in homes without pets.
      Because of the transportability of these allergens on clothing, elevated levels
      in homes without pets, particularly among demographic groups in which pet
      ownership is more prevalent, implicate the community as an important source of
      these pet allergens.

PMID- 15241353
TI  - Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to
      foods, drugs, and insect stings.
AB  - This review highlights some of the research advances in allergic skin disease,
      anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom
      that were reported primarily in the Journal of Allergy and Clinical Immunology
      from 2002 through 2003. Among the topics highlighted are new insights into the
      pathogenesis of atopic dermatitis and potential strategies for more effective
      treatment of the atopic march. Patients should remain supine with raised legs
      during anaphylactic shock because upper body elevation could result in sudden
      death from loss of venous return to the heart. A major advance in food allergy
      was that humanized, monoclonal anti-IgE antibody showed protection against peanut
      induced anaphylaxis. In addition to studies elucidating mechanisms of drug
      hypersensitivity, a clinical study showed patients with a history of prior
      penicillin allergy with negative penicillin allergy test results are unlikely to
      experience reactions or resensitization on subsequent oral courses of penicillin.
      Lastly, there are new recommendations for patients with convincing insect sting
      reaction histories but negative skin test responses to venom.

PMID- 15241354
TI  - You can have fish allergy and eat it too!

PMID- 15241355
TI  - New developments in food allergy: old questions remain.

PMID- 15241356
TI  - Lactobacillus GG effect in increasing IFN-gamma production in infants with cow's
      milk allergy.
AB  - BACKGROUND: Probiotic bacteria are potentially beneficial to maturation of the
      infant's immune system. OBJECTIVE: To examine the role of probiotic bacteria in
      treatment of cow's milk allergy (CMA) and IgE-associated dermatitis, we
      investigated the immunologic effects of Lactobacillus rhamnosus GG (LGG) and a
      mixture of 4 bacterial species (MIX). METHODS: In a randomized, double-blind
      study design, concomitantly with elimination diet and skin treatment, LGG, MIX,
      or placebo was given for 4 weeks to infants with suspected CMA. After anti-CD3
      (OKT3) and anti-CD28 stimulation of PBMCs, IFN-gamma, IL-4, IL-5, and IL-12
      levels were measured in culture supernatants by ELISA. Intracellular IFN-gamma,
      IL-4, and IL-5 production on CD4 lymphocytes was analyzed with fluorescence
      activated cell sorting. RESULTS: Secretion of IFN-gamma by PBMCs before the
      treatment was significantly lower in infants with CMA (P=.016) and in infants
      with IgE-associated CMA (P=.003) than in non-CMA infants. Among the infants who
      received LGG, the level of secreted IFN-gamma increased in those with CMA
      (P=.006) and in those with IgE-associated dermatitis (P=.017) when compared with
      the placebo group. Secretion of IL-4 increased significantly in infants with CMA
      in the MIX (P=.034) but not in the LGG group. CONCLUSION: Deficiency in IFN-gamma
      response appears to be related to CMA. LGG raises IFN-gamma production of PBMC in
      infants with CMA and in infants with IgE-associated dermatitis and may thus
      provide beneficial TH1 immunomodulatory signals. MIX, although containing LGG,
      appears to modulate the immune responses differently.

PMID- 15241357
TI  - Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no
      Langerhans cell apoptosis in patients with atopic dermatitis.
AB  - BACKGROUND: The topical immunomodulators tacrolimus and pimecrolimus are novel
      therapeutic options for atopic dermatitis (AD). The inhibition of nuclear factor
      of activated T cell-dependent proinflammatory cytokine production in cutaneous
      lymphocytes is an established effect of topical immunomodulators, which
      additionally influence mast cells, eosinophils, and dendritic cells (DCs). The
      latter include a reduced expression of the high-affinity IgE receptor
      FcepsilonRI, a reduced stimulatory capacity of lesional DCs, and a selective
      depletion of the inflammatory dendritic epidermal cells (IDECs) but not of
      Langerhans cells (LCs) from the lesional skin. OBJECTIVE: Because induction of
      apoptosis in lymphocytes is a reported tacrolimus effect, we asked whether
      tacrolimus ointment induces apoptosis of LCs or IDECs in AD lesions. METHODS:
      Epidermal single-cell suspensions were prepared from AD lesions of 9 tacrolimus
      treated and 5 hydrocortisone butyrate-treated patients with AD before and after 1
      week of treatment. Cell numbers, apoptosis rate, and immunophenotype were
      assessed by using the standardized FACS technique with terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling, Annexin V, and 3
      color immunophenotyping. Freshly isolated LCs and monocyte-derived DCs served as
      in vitro controls. RESULTS: Tacrolimus and steroid ointment induced a selective
      depletion of IDECs from the epidermis and reduced the expression of the
      costimulatory molecules CD80 and CD86. Tacrolimus ointment did not increase the
      rate of apoptotic DCs, whereas steroid ointment did so. The isolation-induced
      high apoptosis rate of freshly isolated LCs was unaffected by both drugs.
      CONCLUSION: Tacrolimus ointment selectively depletes IDECs and alters the
      immunophenotype of epidermal DCs in AD lesions, but there is no evidence for
      tacrolimus-induced DC apoptosis in this phenomenon.

PMID- 15241358
TI  - The relationship of allergen-specific IgE levels and oral food challenge outcome.
AB  - BACKGROUND: Oral food challenges remain the gold standard for the diagnosis of
      food allergy. However, clear clinical and laboratory guidelines have not been
      firmly established to determine when oral challenges should be performed.
      OBJECTIVE: We sought to determine the value of food-specific IgE levels in
      predicting challenge outcome. METHODS: A retrospective chart review of 604 food
      challenges in 391 children was performed. All children had food-specific IgE
      levels measured by means of CAP-RAST before challenge. Data were analyzed to
      determine the relationship between food-specific IgE levels and challenge
      outcome, as well as the relationship between other clinical parameters and
      challenge outcome. RESULTS: Forty-five percent of milk challenges were passed
      compared with 57% for egg, 59% for peanut, 67% for wheat, and 72% for soy.
      Specific IgE levels were higher among patients who failed challenges than among
      those who passed (P </=.03 for each food). When seeking a specific IgE level at
      which a 50% pass rate could be expected, a cutoff level of 2 kUA/L was determined
      for milk, egg, and peanut. Data were less clear for wheat and soy. Coexistent
      eczema or asthma was associated with failed egg challenges, but other atopic
      disease was otherwise not associated with challenge outcome. CONCLUSIONS:
      Allergen-specific IgE concentrations to milk, egg, and peanut and, to a lesser
      extent, wheat and soy serve as useful predictors of challenge outcome and should
      be considered when selecting patients for oral challenge to these foods.

PMID- 15241359
TI  - How atopic is atopic dermatitis?
AB  - BACKGROUND: The extent to which the phenotype of atopic dermatitis (AD) is truly
      atopic has been the subject of much debate. OBJECTIVE: We sought to
      systematically evaluate the evidence for the value of measurement of IgE
      antibodies in diagnosing AD and whether knowledge of IgE sensitization increases
      clinical diagnostic and predictive ability. METHODS: We searched Medline from its
      inception until September 2003. Only studies that measured atopy as either skin
      prick test positivity or IgE-antibody sensitization to environmental allergens
      were included within a descriptive analysis. Because the small number of studies
      of adequate quality did not allow a formal meta-analysis, we assigned strength of
      evidence according to predefined quality criteria and ranked studies accordingly.
      RESULTS: Inclusion of atopy as part of the diagnostic criteria for AD did not
      enhance the criteria's sensitivity and specificity in relation to the clinical
      phenotype of AD. The strength of association between atopy and AD varied
      significantly between hospital studies (47% to 75%; n=14 studies) and was
      stronger in hospital than in community populations (7.4% to 78%; n=13 studies).
      Whereas study quality did not have an effect on atopy prevalence in hospital
      populations, low atopy prevalences in community surveys were seen in less rigidly
      conducted studies. AD severity was positively associated with the number of
      positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that
      measured both. Only one study suggested that IgE-specific sensitization to hen's
      egg is associated with subsequent development of AD, and 2 studies found that
      allergen-specific IgE sensitization in patients with AD is a prognostic marker
      for allergic airway disease in later life. Atopy-associated AD might also have a
      worse long-term prognosis than AD that is not associated with atopy. CONCLUSION:
      Although atopy is clearly associated with AD, the role of IgE sensitization in AD
      needs further study. Current evidence suggests that up to two thirds of persons
      with AD are not atopic, which implies that continued use of the term atopic
      dermatitis is problematic. Longitudinal studies are needed to compare the
      treatment response and prognosis of IgE-associated and non-IgE-associated AD.

PMID- 15241360
TI  - Prevalence of seafood allergy in the United States determined by a random
      telephone survey.
AB  - BACKGROUND: Seafood allergy is potentially severe, but the prevalence of this
      group of food allergies in the US population has not been determined. OBJECTIVE:
      To estimate the prevalence of seafood (fish, shellfish) allergy in the United
      States. METHODS: We performed a nationwide, cross-sectional, random telephone
      survey by using a standardized questionnaire. Criteria were established in
      advance to define seafood allergy by report of convincing symptoms and physician
      evaluation. RESULTS: A total of 5529 households completed the survey (67.3%
      participation rate), representing a census of 14,948 individuals. Fish or
      shellfish allergy defined by established criteria was reported in 5.9% (95% CI,
      5.3%-6.6%) of households and among individuals as follows: 2.3% (95% CI, 2%-2.5%)
      for any seafood allergy, 2% for shellfish, 0.4% for fish, and 0.2% for both
      types. Seafood allergy was more common in adults compared with children (2.8% vs
      0.6%; P <.001) and in women compared with men (3.6% vs 2%; P <.001). Recurrent
      reactions were reported by 58%, dyspnea or throat tightness was reported by more
      than 50%, and 16% were treated with epinephrine. Despite this level of acuity,
      only 8.6% were prescribed self-injectable epinephrine. The rate of reactions to
      multiple fish among those with any fish allergy was 67%; for Crustacea the rate
      was 38%, and for mollusks the rate was 49%; only 14% with crustacean allergy
      reported a mollusk allergy. CONCLUSIONS: Physician-diagnosed and/or convincing
      seafood allergy is reported by 2.3% of the general population, or approximately
      6.6 million Americans. Affected individuals typically report recurrent and
      sometimes severe reactions, indicating that seafood allergy represents a
      significant health concern.

PMID- 15241361
TI  - Essential role of dendritic cell CD80/CD86 costimulation in the induction, but
      not reactivation, of TH2 effector responses in a mouse model of asthma.
AB  - BACKGROUND: Airway dendritic cells (DCs) are crucial for the generation of TH2
      cells from naive T cells during sensitization and for reactivation of primed TH2
      cells on allergen challenge in mouse models of asthma. It is unknown whether
      CD80/CD86 costimulation is necessary during both phases of the response because
      primed T cells rely less on costimulatory molecules compared with naive T cells.
      OBJECTIVE: We sought to study the contribution of CD80/CD86 costimulatory
      molecules on DCs during sensitization or challenge in a mouse model of asthma.
      METHODS: Naive BALB/c mice received an intratracheal injection of ovalbumin (OVA)
      pulsed DCs obtained from the bone marrow of wild-type (WT) or CD80/CD86-/- mice
      and were subsequently challenged with OVA aerosol to address the role of
      costimulation during sensitization. OVA-sensitized mice received OVA-pulsed WT or
      CD80/CD86-/- DCs without OVA aerosol to address the role of costimulation during
      challenge. RESULTS: WT DCs induced the proliferation and effector TH2
      differentiation of naive OVA-specific T cells, whereas CD80/CD86-/- DCs induced
      only proliferation. Not surprisingly, WT DCs but not CD80/CD86-/- DCs induced
      sensitization to OVA in naive mice. In contrast, in OVA-sensitized mice
      intratracheal injection of CD80/CD86-/- OVA-pulsed DCs led to eosinophilic airway
      inflammation, goblet cell hyperplasia, and effector TH2 cytokine production that
      was not different from that seen after injection with WT OVA-DCs, even when the
      inducible costimulator ICOS was blocked or cytotoxic T lymphocyte-associated
      antigen 4 immunoglobulin was given. CONCLUSION: CD80/CD86 costimulation on DCs is
      only necessary during priming of naive T cells into TH2 cells but not during
      restimulation of previously primed TH2 cells in the challenge phase.

PMID- 15241362
TI  - Activation of mast cells by double-stranded RNA: evidence for activation through
      Toll-like receptor 3.
AB  - BACKGROUND: Although mast cells (MCs) have been clearly implicated in innate
      immune responses involving bacteria, their ability to respond to viral infection
      is less clear. OBJECTIVE: Given that MCs increase at sites of inflammation and
      are located at surfaces where exposure to invading viruses may occur, we explored
      the ability of MCs to produce cytokines including type I IFNs after exposure to
      viruses and to polyinosine-polycytidylic acid (polyI:C), a synthetic mimic of
      viral double-stranded RNA, and characterized the receptors involved, if any.
      METHODS: Human peripheral blood-derived cultured MCs and 2 MC lines, Laboratory
      of Allergic Disease MC line and human MC line 1, were stimulated with viruses and
      polyI:C, and cytokine production, degranulation, and signaling pathway activation
      were examined. Because polyI:C is a ligand for Toll-like receptor (TLR)-3, human
      MCs were also analyzed for TLR expression. RESULTS: Viruses and polyI:C induced
      IFN-alpha and IFN-beta production. PolyI:C did not induce TNF, IL-1beta, IL-5, or
      GM-CSF production, in contrast with other TLR ligands (LPS, peptidoglycan, CpG-A,
      or flagellin). IFN-alpha production involved nuclear factor-kappaB, p38, and C
      Jun NH2-terminal kinase and mitogen-activated protein kinase. RT-PCR and Western
      blot analysis confirmed expression of TLR-3 by all MCs. Human cultured MCs also
      expressed TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-7 and TLR-9. Antibodies to TLR-3
      significantly decreased IFN-alpha production. Bone marrow-derived MCs from TLR-3
      knockout mice showed an ablated response to polyI:C. CONCLUSIONS: Murine and
      human MCs produce type I IFNs after exposure to double-stranded RNA and/or virus,
      the former via specific interactions with TLR-3. These data suggest that MCs
      contribute to innate immune responses to viral infection via the production of
      type I IFNs.

PMID- 15241371
TI  - News cornucopia.

PMID- 15241363
TI  - Differential control of TH1 versus TH2 cell responses by the combination of low
      dose steroids with beta2-adrenergic agonists.
AB  - BACKGROUND: Combination treatment with steroids and long-acting beta2-agonists
      provides greater asthma control than simply increasing the dose of steroids.
      OBJECTIVE: Although the effects of combination treatment with steroids and long
      acting beta2-agonists have been attributed to their anti-inflammatory and
      bronchodilator effects, the ability of this combination to act synergistically on
      T cells has not been explored. METHODS: PBMCs from control subjects and allergic
      asthmatic patients were stimulated with PHA in the presence of low doses of
      fluticasone propionate (FP) with or without salmeterol for 72 hours. The
      inhibition of T-cell proliferation, cytokine production, and glucocorticoid
      receptor translocation was measured. RESULTS: Both groups showed a similar degree
      of inhibition of PHA-induced T-cell proliferation with FP (inhibitory
      concentration of 50% approximately 10(-9) mol/L) alone. Use of lower
      concentrations of FP (10(-12) to 10(-11) mol/L) in combination with salmeterol
      (10(-10) to 10(-7) mol/L) in control subjects provided similar inhibition of
      proliferation. This combination treatment was associated with significantly
      greater glucocorticoid receptor translocation into the cell nucleus compared with
      that seen with FP alone (10(-12) mol/L; P <.01). In contrast, FP-salmeterol
      failed to act synergistically in asthmatic patients. The 2-drug combination
      significantly inhibited production of TNF-alpha and IFN-gamma in both groups (P
      <.05) but failed to inhibit TH2 cytokine (IL-5 and IL-13) production by PBMCs
      from asthmatic patients. Because allergic inflammation is associated with
      increased levels of cellular phosphodiesterases that might degrade salmeterol
      induced cyclic adenosine monophosphate, rolipram (10(-6) mol/L), a
      phosphodiesterase 4 inhibitor, was added to the FP-salmeterol combination. This
      triple combination of drugs enhanced inhibitory activity of low-dose steroids on
      T-cell proliferation in asthmatic patients and inhibited IL-13 production.
      CONCLUSION: These data suggest that beta2-agonists in combination with low doses
      of steroids can suppress T-cell proliferation and TH1 cytokine production from
      healthy individuals, but suppression of T cells with a combination of FP and
      salmeterol in asthmatic patients requires inhibition of phosphodiesterases.

PMID- 15241370
TI  - Beyond Cassini.

PMID- 15241372
TI  - War of words escalates in run-up to California's vote on stem cells.

PMID- 15241374
TI  - Scepticism greets pitch to detect dark energy in the lab.

PMID- 15241373
TI  - Superbug genome excels at passing on drug resistance.

PMID- 15241375
TI  - Treetop ecologists brought down by miners.

PMID- 15241376
TI  - 'Inspirational' leader quits Madrid heart project.

PMID- 15241377
TI  - Biochemist takes the reins at top European laboratory.

PMID- 15241378
TI  - Low US participation clouds AIDS meeting.

PMID- 15241379
TI  - Senator urges private groups to run cut-price Moon shot.

PMID- 15241380
TI  - Watchdog slams failings of Israeli animal-rights law.

PMID- 15241383
TI  - Snapshot of a pandemic.

PMID- 15241382
TI  - Called to account.

PMID- 15241384
TI  - Out of Thailand, into Africa.

PMID- 15241385
TI  - Starting to gel.

PMID- 15241386
TI  - Extinction-risk coverage is worth inaccuracies.

PMID- 15241387
TI  - Saving vital time in the war on drug resistance.

PMID- 15241388
TI  - Fat chance of measuring food intake accurately.

PMID- 15241389
TI  - The fight for fair play.

PMID- 15241395
TI  - Old before their time.

PMID- 15241396
TI  - Immunology: polarizing a T-cell response.

PMID- 15241397
TI  - Earth science: kinks and circuits.

PMID- 15241399
TI  - Ion channels: gate expectations.

PMID- 15241400
TI  - Condensed-matter physics: charge-ordering in oxides.

PMID- 15241401
TI  - Immunology: another manifestation of GOD.

PMID- 15241403
TI  - The RNAi revolution.

PMID- 15241404
TI  - Braiding patterns on an inclined plane.
AB  - A jet of fluid flowing down a partially wetting, inclined plane usually meanders
      but--by maintaining a constant flow rate--meandering can be suppressed, leading
      to the emergence of a beautiful braided structure. Here we show that this flow
      pattern can be explained by the interplay between surface tension, which tends to
      narrow the jet, and fluid inertia, which drives the jet to widen. These
      observations dispel misconceptions about the relationship between braiding and
      meandering that have persisted for over 20 years.

PMID- 15241405
TI  - Prediction of Emperor-Hawaii seamount locations from a revised model of global
      plate motion and mantle flow.
AB  - The bend in the Hawaiian-Emperor seamount chain is a prominent feature usually
      attributed to a change in Pacific plate motion approximately 47 Myr ago. However,
      global plate motion reconstructions fail to predict the bend. Here we show how
      the geometry of the Hawaiian-Emperor chain and other hotspot tracks can be
      explained when we combine global plate motions with intraplate deformation and
      movement of hotspot plumes through distortion by global mantle flow. Global
      mantle flow models predict a southward motion of the Hawaiian hotspot. This, in
      combination with a plate motion reconstruction connecting Pacific and African
      plates through Antarctica, predicts the Hawaiian track correctly since the date
      of the bend, but predicts the chain to be too far west before it. But if a
      reconstruction through Australia and Lord Howe rise is used instead, the track is
      predicted correctly back to 65 Myr ago, including the bend. The difference
      between the two predictions indicates the effect of intraplate deformation not
      yet recognized or else not recorded on the ocean floor. The remaining misfit
      before 65 Myr ago can be attributed to additional intraplate deformation of
      similar magnitude.

PMID- 15241406
TI  - Somatic diversification of variable lymphocyte receptors in the agnathan sea
      lamprey.
AB  - Although jawless vertebrates are apparently capable of adaptive immune responses,
      they have not been found to possess the recombinatorial antigen receptors shared
      by all jawed vertebrates. Our search for the phylogenetic roots of adaptive
      immunity in the lamprey has instead identified a new type of variable lymphocyte
      receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched
      between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the
      VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To
      generate rearranged VLR genes of the diversity necessary for an anticipatory
      immune system, the single lamprey VLR locus contains a large bank of diverse LRR
      cassettes, available for insertion into an incomplete germline VLR gene.
      Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic
      fashion. Different evolutionary strategies were thus used to generate highly
      diverse lymphocyte receptors through rearrangement of LRR modules in agnathans
      (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed
      vertebrates).

PMID- 15241407
TI  - A high abundance of massive galaxies 3-6 billion years after the Big Bang.
AB  - Hierarchical galaxy formation is the model whereby massive galaxies form from an
      assembly of smaller units. The most massive objects therefore form last. The
      model succeeds in describing the clustering of galaxies, but the evolutionary
      history of massive galaxies, as revealed by their visible stars and gas, is not
      accurately predicted. Near-infrared observations (which allow us to measure the
      stellar masses of high-redshift galaxies) and deep multi-colour images indicate
      that a large fraction of the stars in massive galaxies form in the first 5 Gyr
      (refs 4-7), but uncertainties remain owing to the lack of spectra to confirm the
      redshifts (which are estimated from the colours) and the role of obscuration by
      dust. Here we report the results of a spectroscopic redshift survey that probes
      the most massive and quiescent galaxies back to an era only 3 Gyr after the Big
      Bang. We find that at least two-thirds of massive galaxies have appeared since
      this era, but also that a significant fraction of them are already in place in
      the early Universe.

PMID- 15241408
TI  - Old galaxies in the young Universe.
AB  - More than half of all stars in the local Universe are found in massive spheroidal
      galaxies, which are characterized by old stellar populations with little or no
      current star formation. In present models, such galaxies appear rather late in
      the history of the Universe as the culmination of a hierarchical merging process,
      in which larger galaxies are assembled through mergers of smaller precursor
      galaxies. But observations have not yet established how, or even when, the
      massive spheroidals formed, nor if their seemingly sudden appearance when the
      Universe was about half its present age (at redshift z approximately 1) results
      from a real evolutionary effect (such as a peak of mergers) or from the
      observational difficulty of identifying them at earlier epochs. Here we report
      the spectroscopic and morphological identification of four old, fully assembled,
      massive (10(11) solar masses) spheroidal galaxies at l.6 < z < 1.9, the most
      distant such objects currently known. The existence of such systems when the
      Universe was only about one-quarter of its present age shows that the build-up of
      massive early-type galaxies was much faster in the early Universe than has been
      expected from theoretical simulations.

PMID- 15241409
TI  - An unusual isotope effect in a high-transition-temperature superconductor.
AB  - In conventional superconductors, the electron pairing that allows
      superconductivity is caused by exchange of virtual phonons, which are quanta of
      lattice vibration. For high-transition-temperature (high-T(c)) superconductors,
      it is far from clear that phonons are involved in the pairing at all. For
      example, the negligible change in T(c) of optimally doped Bi2Sr2CaCu2O8+delta
      (Bi2212; ref. 1) upon oxygen isotope substitution (16O --> 18O leads to T(c)
      decreasing from 92 to 91 K) has often been taken to mean that phonons play an
      insignificant role in this material. Here we provide a detailed comparison of the
      electron dynamics of Bi2212 samples containing different oxygen isotopes, using
      angle-resolved photoemission spectroscopy. Our data show definite and strong
      isotope effects. Surprisingly, the effects mainly appear in broad high-energy
      humps, commonly referred to as 'incoherent peaks'. As a function of temperature
      and electron momentum, the magnitude of the isotope effect closely correlates
      with the superconducting gap--that is, the pair binding energy. We suggest that
      these results can be explained in a dynamic spin-Peierls picture, where the
      singlet pairing of electrons and the electron-lattice coupling mutually enhance
      each other.

PMID- 15241410
TI  - Colloidal nanocrystal heterostructures with linear and branched topology.
AB  - The development of colloidal quantum dots has led to practical applications of
      quantum confinement, such as in solution-processed solar cells, lasers and as
      biological labels. Further scientific and technological advances should be
      achievable if these colloidal quantum systems could be electronically coupled in
      a general way. For example, this was the case when it became possible to couple
      solid-state embedded quantum dots into quantum dot molecules. Similarly, the
      preparation of nanowires with linear alternating compositions--another form of
      coupled quantum dots--has led to the rapid development of single-nanowire light
      emitting diodes and single-electron transistors. Current strategies to connect
      colloidal quantum dots use organic coupling agents, which suffer from limited
      control over coupling parameters and over the geometry and complexity of
      assemblies. Here we demonstrate a general approach for fabricating inorganically
      coupled colloidal quantum dots and rods, connected epitaxially at branched and
      linear junctions within single nanocrystals. We achieve control over branching
      and composition throughout the growth of nanocrystal heterostructures to
      independently tune the properties of each component and the nature of their
      interactions. Distinct dots and rods are coupled through potential barriers of
      tuneable height and width, and arranged in three-dimensional space at well
      defined angles and distances. Such control allows investigation of potential
      applications ranging from quantum information processing to artificial
      photosynthesis.

PMID- 15241411
TI  - Export of dissolved organic carbon from peatlands under elevated carbon dioxide
      levels.
AB  - Peatlands represent a vast store of global carbon. Observations of rapidly rising
      dissolved organic carbon concentrations in rivers draining peatlands have created
      concerns that those stores are beginning to destabilize. Three main factors have
      been put forward as potential causal mechanisms, but it appears that two
      alternatives--warming and increased river discharge--cannot offer satisfactory
      explanations. Here we show that the third proposed mechanism, namely shifting
      trends in the proportion of annual rainfall arriving in summer, is similarly
      unable to account for the trend. Instead we infer that a previously unrecognized
      mechanism--carbon dioxide mediated stimulation of primary productivity--is
      responsible. Under elevated carbon dioxide levels, the proportion of dissolved
      organic carbon derived from recently assimilated carbon dioxide was ten times
      higher than that of the control cases. Concentrations of dissolved organic carbon
      appear far more sensitive to environmental drivers that affect net primary
      productivity than those affecting decomposition alone.

PMID- 15241412
TI  - Unexpectedly recent dates for human remains from Vogelherd.
AB  - The human skeletal remains from the Vogelherd cave in the Swabian Jura of
      southwestern Germany are at present seen as the best evidence that modern humans
      produced the artefacts of the early Aurignacian. Radiocarbon measurements from
      all the key fossils from Vogelherd show that these human remains actually date to
      the late Neolithic, between 3,900 and 5,000 radiocarbon years before present
      (bp). Although many questions remain unresolved, these results weaken the
      arguments for the Danube Corridor hypothesis--that there was an early migration
      of modern humans into the Upper Danube drainage--and strengthen the view that
      Neanderthals may have contributed significantly to the development of Upper
      Palaeolithic cultural traits independent of the arrival of modern humans.

PMID- 15241413
TI  - Origin of extant domesticated sunflowers in eastern North America.
AB  - Eastern North America is one of at least six regions of the world where
      agriculture is thought to have arisen wholly independently. The primary evidence
      for this hypothesis derives from morphological changes in the archaeobotanical
      record of three important crops--squash, goosefoot and sunflower--as well as an
      extinct minor cultigen, sumpweed. However, the geographical origins of two of the
      three primary domesticates--squash and goosefoot--are now debated, and until
      recently sunflower (Helianthus annuus L.) has been considered the only undisputed
      eastern North American domesticate. The discovery of 4,000-year-old domesticated
      sunflower remains from San Andres, Tabasco, implies an earlier and possibly
      independent origin of domestication in Mexico and has stimulated a re-examination
      of the geographical origin of domesticated sunflower. Here we describe the
      genetic relationships and pattern of genetic drift between extant domesticated
      strains and wild populations collected from throughout the USA and Mexico. We
      show that extant domesticates arose in eastern North America, with a substantial
      genetic bottleneck occurring during domestication.

PMID- 15241414
TI  - Evolutionary change from induced to constitutive expression of an indirect plant
      resistance.
AB  - Induced plant resistance traits are expressed in response to attack and occur
      throughout the plant kingdom. Despite their general occurrence, the evolution of
      such resistances has rarely been investigated. Here we report that extrafloral
      nectar, a usually inducible trait, is constitutively secreted by Central American
      Acacia species that are obligately inhabited by ants. Extrafloral nectar is
      secreted as an indirect resistance, attracting ants that defend plants against
      herbivores. Leaf damage induces extrafloral nectar secretion in several plant
      species; among these are various Acacia species and other Fabaceae investigated
      here. In contrast, Acacia species obligately inhabited by symbiotic ants nourish
      these ants by secreting extrafloral nectar constitutively at high rates that are
      not affected by leaf damage. The phylogeny of the genus Acacia and closely
      related genera indicate that the inducibility of extrafloral nectar is the
      plesiomorphic or 'original' state, whereas the constitutive extrafloral nectar
      flow is derived within Acacia. A constitutive resistance trait has evolved from
      an inducible one, obviously in response to particular functional demands.

PMID- 15241416
TI  - Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible
      nuclear protein IkappaBzeta.
AB  - Toll-like receptors (TLRs) recognize microbial components and trigger the
      inflammatory and immune responses against pathogens. IkappaBzeta (also known as
      MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly
      homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of
      IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1
      (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a
      subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient
      cells show severe impairment of IL-6 production in response to a variety of TLR
      ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha.
      Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB,
      and is recruited to the NF-kappaB binding site of the IL-6 promoter on
      stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R
      ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced
      expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta
      deficient macrophages. Given that the lipopolysaccharide-induced transcription of
      IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R
      mediated responses may be regulated in a gene expression process of at least two
      steps that requires inducible IkappaBzeta.

PMID- 15241415
TI  - Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in
      eastern Asia.
AB  - A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in
      poultry in China and seven other east Asian countries between late 2003 and early
      2004; the same virus was fatal to humans in Thailand and Vietnam. Here we
      demonstrate a series of genetic reassortment events traceable to the precursor of
      the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997
      (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These
      events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was
      responsible for the regional outbreak in 2003-04. Our findings indicate that
      domestic ducks in southern China had a central role in the generation and
      maintenance of this virus, and that wild birds may have contributed to the
      increasingly wide spread of the virus in Asia. Our results suggest that H5N1
      viruses with pandemic potential have become endemic in the region and are not
      easily eradicable. These developments pose a threat to public and veterinary
      health in the region and potentially the world, and suggest that long-term
      control measures are required.

PMID- 15241417
TI  - Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing
      factors.
AB  - During transcription, RNA polymerase (Pol) II synthesizes eukaryotic messenger
      RNA. Transcription is coupled to RNA processing by the carboxy-terminal domain
      (CTD) of Pol II, which consists of up to 52 repeats of the sequence Tyr 1-Ser 2
      Pro 3-Thr 4-Ser 5-Pro 6-Ser 7 (refs 1, 2). After phosphorylation, the CTD binds
      tightly to a conserved CTD-interacting domain (CID) present in the proteins Pcf11
      and Nrd1, which are essential and evolutionarily conserved factors for
      polyadenylation-dependent and -independent 3'-RNA processing, respectively. Here
      we describe the structure of a Ser 2-phosphorylated CTD peptide bound to the CID
      domain of Pcf11. The CTD motif Ser 2-Pro 3-Thr 4-Ser 5 forms a beta-turn that
      binds to a conserved groove in the CID domain. The Ser 2 phosphate group does not
      make direct contact with the CID domain, but may be recognized indirectly because
      it stabilizes the beta-turn with an additional hydrogen bond. Iteration of the
      peptide structure results in a compact beta-spiral model of the CTD. The model
      suggests that, during the mRNA transcription-processing cycle, compact spiral
      regions in the CTD are unravelled and regenerated in a phosphorylation-dependent
      manner.

PMID- 15241418
TI  - Cyclin-dependent kinases regulate the antiproliferative function of Smads.
AB  - Transforming growth factor-beta (TGF-beta) potently inhibits cell cycle
      progression at the G1 phase. Smad3 has a key function in mediating the TGF-beta
      growth-inhibitory response. Here we show that Smad3 is a major physiological
      substrate of the G1 cyclin-dependent kinases CDK4 and CDK2. Except for the
      retinoblastoma protein family, Smad3 is the only CDK4 substrate demonstrated so
      far. We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser
      212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3
      transcriptional activity, leading to higher expression of the CDK inhibitor p15.
      Mutation of the CDK phosphorylation sites of Smad3 also increases its ability to
      downregulate the expression of c-myc. Using Smad3(-/-) mouse embryonic
      fibroblasts and other epithelial cell lines, we further show that Smad3 inhibits
      cell cycle progression from G1 to S phase and that mutation of the CDK
      phosphorylation sites in Smad3 increases this ability. Taken together, these
      findings indicate that CDK phosphorylation of Smad3 inhibits its transcriptional
      activity and antiproliferative function. Because cancer cells often contain high
      levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may
      contribute to tumorigenesis and TGF-beta resistance in cancers.

PMID- 15241419
TI  - A membrane-access mechanism of ion channel inhibition by voltage sensor toxins
      from spider venom.
AB  - Venomous animals produce small protein toxins that inhibit ion channels with high
      affinity. In several well-studied cases the inhibitory proteins are water-soluble
      and bind at a channel's aqueous-exposed extracellular surface. Here we show that
      a voltage-sensor toxin (VSTX1) from the Chilean Rose Tarantula (Grammostola
      spatulata) reaches its target by partitioning into the lipid membrane. Lipid
      membrane partitioning serves two purposes: to localize the toxin in the membrane
      where the voltage sensor resides and to exploit the free energy of partitioning
      to achieve apparent high-affinity inhibition. VSTX1, small hydrophobic poisons
      and anaesthetic molecules reveal a common theme of voltage sensor inhibition
      through lipid membrane access. The apparent requirement for such access is
      consistent with the recent proposal that the sensor in voltage-dependent K+
      channels is located at the membrane-protein interface.

PMID- 15241420
TI  - Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide
      enantiomers.
AB  - The peptide GsMTx4, isolated from the venom of the tarantula Grammostola
      spatulata, is a selective inhibitor of stretch-activated cation channels (SACs).
      The mechanism of inhibition remains unknown; but both GsMTx4 and its enantiomer,
      enGsMTx4, modify the gating of SACs, thus violating a trademark of the
      traditional lock-and-key model of ligand-protein interactions. Suspecting a
      bilayer-dependent mechanism, we examined the effect of GsMTx4 and enGsMTx4 on
      gramicidin A (gA) channel gating. Both peptides are active, and the effect
      increases with the degree of hydrophobic mismatch between bilayer thickness and
      channel length, meaning that GsMTx4 decreases the energy required to deform the
      boundary lipids adjacent to the channel. GsMTx4 decreases inward SAC single
      channel currents but has no effect on outward currents, suggesting it is located
      within a Debye length of the outer vestibule of the SACs, but significantly
      farther from the inner vestibule. Likewise, GsMTx4 decreases gA single-channel
      currents. Our results suggest that modulation of membrane proteins by amphipathic
      peptides--mechanopharmacology--involves not only the protein itself but also the
      surrounding lipids. The surprising efficacy of the d form of GsMTx4 peptide has
      important therapeutic implications, because d peptides are not hydrolysed by
      endogenous proteases and may be administered orally.

PMID- 15241422
TI  - The challenge of emerging and re-emerging infectious diseases.
AB  - Infectious diseases have for centuries ranked with wars and famine as major
      challenges to human progress and survival. They remain among the leading causes
      of death and disability worldwide. Against a constant background of established
      infections, epidemics of new and old infectious diseases periodically emerge,
      greatly magnifying the global burden of infections. Studies of these emerging
      infections reveal the evolutionary properties of pathogenic microorganisms and
      the dynamic relationships between microorganisms, their hosts and the
      environment.

PMID- 15241424
TI  - Inferences, questions and possibilities in Toll-like receptor signalling.
AB  - The Toll-like receptors (TLRs) are the key proteins that allow mammals--whether
      immunologically naive or experienced--to detect microbes. They lie at the core of
      our inherited resistance to disease, initiating most of the phenomena that occur
      in the course of infection. Quasi-infectious stimuli that have been used for
      decades to study inflammatory mechanisms can activate the TLR family of proteins.
      And it now seems that many inflammatory processes, both sterile and infectious,
      may depend on TLR signalling. We are in a good position to apply our
      understanding of TLR signalling to a range of challenges in immunology and
      medicine.

PMID- 15241423
TI  - Frontal and stealth attack strategies in microbial pathogenesis.
AB  - Interactions between microbes and human hosts can range from a benign, even
      symbiotic collaboration to a competition that may turn fatal--resulting in death
      of the host, the microbe or both. Despite advances that have been made over the
      past decades in understanding microbial pathogens, more people worldwide still
      die every year from infectious disease than from any other cause. This highlights
      the relevance of continuing to probe the mechanisms used by microorganisms to
      cause disease, and emphasizes the need for new model systems to advance our
      understanding of host-pathogen interactions.

PMID- 15241425
TI  - Translating cell biology in vitro to immunity in vivo.
AB  - The elimination of pathogens and pathogen-infected cells initially rests on the
      rapid deployment of innate immune defences. Should these defences fail, it is the
      lymphocytes--T cells and B cells--with their antigen-specific receptors that must
      rise to the task of providing adaptive immunity. Technological advances are now
      allowing immunologists to correlate data obtained in vitro with in vivo
      functions. A better understanding of T-cell activation in vivo could lead to more
      effective strategies for the treatment and prevention of infectious and
      autoimmmune diseases.

PMID- 15241427
TI  - Coming back to life Montreal.

PMID- 15241429
TI  - Recruiters and industry. Building biostatistics.

PMID- 15241432
TI  - Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci
      for bipolar disorder and shared susceptibility with schizophrenia.
AB  - The low-to-moderate resolution of linkage analysis in complex traits has
      underscored the need to identify disease phenotypes with presumed genetic
      homogeneity. Bipolar disorder (BP) accompanied by psychosis (psychotic BP) may be
      one such phenotype. We previously reported a genome-wide screen in a large
      bipolar pedigree sample. In this follow-up study, we reclassified the disease
      phenotype based on the presence or absence of psychotic features and subgrouped
      pedigrees according to familial load of psychosis. Evidence for significant
      linkage to psychotic BP (genome-wide P<0.05) was obtained on chromosomes 9q31
      (lod=3.55) and 8p21 (lod=3.46). Several other sites were supportive of linkage,
      including 5q33 (lod=1.78), 6q21 (lod=1.81), 8p12 (lod=2.06), 8q24 (lod=2.01),
      13q32 (lod=1.96), 15q26 (lod=1.96), 17p12 (lod=2.42), 18q21 (lod=2.4), and 20q13
      (lod=1.98). For most loci, the highest lod scores, including those with genome
      wide significance (at 9q31 and 8p21), occurred in the subgroup of families with
      the largest concentration of psychotic individuals (> or =3 in a family).
      Interestingly, all regions but six--5q33, 6q21, 8p21, 8q24, 13q32 and 18q21-
      appear to be novel; namely, they did not show notable linkage to BP in other
      genome scans, which did not employ psychosis for disease classification. Also of
      interest is possible overlap with schizophrenia, another major psychotic
      disorder: seven of the regions presumed linked in this study--5q, 6q, 8p, 13q,
      15q, 17p, and 18q--are also implicated in schizophrenia, as are 2p13 and 10q26,
      which showed more modest support for linkage. Our results suggest that BP in
      conjunction with psychosis is a potentially useful phenotype that may: (1)
      expedite the detection of susceptibility loci for BP and (2) cast light on the
      genetic relationship between BP and schizophrenia.

PMID- 15241431
TI  - Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean
      Hispanics.
AB  - Familial Alzheimer's disease (AD [MIM 104300]) has been a focus of intense
      investigation, primarily in Caucasian families from Europe and North America
      families. Although the late-onset form of familial AD, beginning after age 65
      years, has been linked to regions on chromosomes 10q and 12p, the specific
      genetic variants have not yet been consistently identified. Using a unique cohort
      of families of Caribbean Hispanics ancestry, we screened the genome using 340
      markers on 490 family members from 96 families with predominantly late-onset AD.
      We observed the strongest support for linkage on 18q (LOD=3.14). However, 17
      additional markers (chromosomes 1-6, 8, 10, 12, and 14) exceeded a two-point LOD
      score of 1.0 under the affecteds-only autosomal dominant model or affected
      sibpair model. As we previously reported the fine-mapping effort on 12p showing
      modest evidence of linkage, we focused our fine-mapping efforts on two other
      candidate regions in the current report, namely 10q and 18q. We added 31 family
      members and eight additional Caribbean Hispanic families to fine map 10q and 18q.
      With additional microsatellite markers, the evidence for linkage for 18q
      strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and
      the highest NPL score in that region was 3.65 (P=0.000177). This narrow region
      contains a small number of genes expressed in the brain. However, at 10q (134-138
      cM), the NPL score decreased from 3.15 (P=0.000486) to 2.1 (P=0.0218), but two
      broad peaks remained overlapping with previously reported peaks. Our results
      provide modest support for linkage on 10q and 12p in this cohort of Caribbean
      Hispanic families with familial Alzheimer's disease, and strong evidence for a
      new locus on 18q.

PMID- 15241433
TI  - PANDAS: current status and directions for research.
AB  - The recognition of the five criteria for PANDAS (pediatric autoimmune
      neuropsychiatric disorders associated with streptococcal infections) by Swedo et
      al established a homogenous subgroup of children with childhood onset obsessive
      compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics
      that define the PANDAS subgroup are the presence of OCD and/or tic disorder,
      prepubertal age of onset, abrupt onset and relapsing-remitting symptom course,
      association with neurological abnormalities during exacerbations (adventitious
      movements or motoric hyperactivity), and a temporal association between symptom
      exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These
      five criteria have been used for the purpose of systematic research on the
      phenomenology and unique therapies for the PANDAS subgroup as well as studies of
      the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of
      OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a
      result of post-streptococcal autoimmunity in a manner similar to that of
      Sydenham's chorea. The working hypothesis for the pathophysiology begins with a
      GAS infection in a susceptible host that incites the production of antibodies to
      GAS that crossreact with the cellular components of the basal ganglia,
      particularly in the caudate nucleus and putamen. The obsessions, compulsions,
      tics, and other neuropsychiatric symptoms seen in these children are postulated
      to arise from an interaction of these antibodies with neurons of the basal
      ganglia.

PMID- 15241434
TI  - Influenza A virus infection causes alterations in expression of synaptic
      regulatory genes combined with changes in cognitive and emotional behaviors in
      mice.
AB  - Epidemiological studies have indicated a link between certain neuropsychiatric
      diseases and exposure to viral infections. In order to examine long-term effects
      on behavior and gene expression in the brain of one candidate virus, we have used
      a model involving olfactory bulb injection of the neuro-adapted influenza A virus
      strain, WSN/33, in C57Bl/6 mice. Following this olfactory route of invasion, the
      virus targets neurons in the medial habenular, midline thalamic and hypothalamic
      nuclei as well as monoaminergic neurons in the brainstem. The mice survive and
      the viral infection is cleared from the brain within 12 days. When tested 14-20
      weeks after infection, the mice displayed decreased anxiety in the elevated plus
      maze and impaired spatial learning in the Morris water maze test. Elevated
      transcriptional activity of two genes encoding synaptic regulatory proteins,
      regulator of G-protein signaling 4 and calcium/calmodulin-dependent protein
      kinase IIalpha, was found in the amygdala, hypothalamus and cerebellum. It is of
      particular interest that the gene encoding RGS4, which has been related to
      schizophrenia, showed the most pronounced alteration. This study indicates that a
      transient influenza virus infection can cause persistent changes in emotional and
      cognitive functions as well as alterations in the expression of genes involved in
      the regulation of synaptic activities.

PMID- 15241435
TI  - Gene-environment interaction analysis of serotonin system markers with adolescent
      depression.
AB  - We report analyses from a study of gene-environment interaction in adolescent
      depression. The sample was selected from 1990 adolescents aged 10-20 years: those
      with depression symptoms in the top or bottom 15% were identified and divided
      into high or low environmental risk groups. DNA was obtained from 377
      adolescents, representing the four quadrants of high or low depression and high
      or low environmental risk. Markers within, or close to, each of the serotonergic
      genes 5HTT, HTR2A, HTR2C, MAOA (monoamine oxidase type A) and tryptophan
      hydroxylase (TPH) were genotyped. Environmental risk group was a nonsignificant
      predictor and sex was a significant predictor of the depression group. HTR2A and
      TPH significantly predicted the depression group, independent of the effects of
      sex, environmental risk group and their interaction. In addition, there was a
      trend for an effect of 5HTTLPR, which was significant in female subjects.
      Furthermore, there was a significant genotype-environmental risk interaction for
      5HTTLPR in female subjects only, with the effect being in the same direction as
      another recent study, reaffirming that an important source of genetic
      heterogeneity is exposure to environmental risk.

PMID- 15241436
TI  - Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF.

PMID- 15241437
TI  - BCR-ABL transcripts are early predictors for hematological relapse in chronic
      myeloid leukemia after hematopoietic cell transplantation with reduced intensity
      conditioning.
AB  - Kinetics of BCR-ABL transcript elimination and its prognostic implications on
      relapse were analyzed in patients with chronic myeloid leukemia (CML) after
      reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML
      patients were conditioned with 2 Gy total-body irradiation in combination with
      (n=14) or without (n=3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid
      irradiation (TLI) with Flu and OKT3 3 x 5 mg (n=2) and were treated with
      cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL
      transcripts were analyzed by nested RT-PCR and Taqman((R)) RT-PCR on days +28,
      +56 and +84 after HCT and were evaluated for their association with relapse. Of
      the 19 patients, 14 achieved sustained remissions of which six had a negative RT
      PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days
      after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow
      reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post
      transplant. We conclude that a complete clearance of BCR-ABL transcripts is
      achievable within 4 weeks from HCT even after minimal conditioning and that early
      kinetics of BCR-ABL transcripts significantly correlate with the probability of
      hematological relapse.

PMID- 15241438
TI  - Osteoprotegerin serum levels in multiple myeloma and MGUS patients compared with
      age- and sex-matched healthy controls.

PMID- 15241439
TI  - Graft-versus-myeloma: are durable responses a clinical reality following donor
      lymphocyte infusion?

PMID- 15241441
TI  - Epstein-Barr virus is integrated between REL and BCL-11A in American Burkitt
      lymphoma cell line (NAB-2).
AB  - Epstein-Barr virus (EBV) initially isolated from the cultured Burkitt lymphoma
      (BL) cells, is one of the well-known oncogenic virus. The NAB-2 line, which was
      established from a North American Burkitt's tumor, was indicated to contain one
      copy of EBV DNA as the integrated form into chromosome 2p13 of the host genome.
      To demonstrate the integration site of EBV directly, and to clarify the relation
      between the integration sites and the oncogenes, fragments containing the
      nucleotide sequence of NAB-2 integration sites were cloned. EBV was integrated
      via the terminal repeats (TR), and integration sites located in the clone RP11
      440P5 on chromosome 2, between two oncogenes, REL and BCL11A, which is apart from
      approximately 350 kbp from each other. Expression level of REL in NAB-2 was
      increased. The flanking region of chromosome 2 at the bilateral junction sites
      showed no homology to the junction sites of EBV. The integration site 2p13
      overlaps with common fragile site, FRA2E. NAB-2 cells expressed almost all latent
      genes but LMP-2A that flanks the TR, indicating the type III of latent infection
      of EBV. Integration event in NAB-2 might alter the regulation of the oncogenes
      and provide advantage for continuous cell proliferation.

PMID- 15241442
TI  - Isolated ambulatory hypertension is common in outpatients referred to a
      hypertension centre.
AB  - The present investigation was aimed at determining the prevalence and the blood
      pressure (BP) profile of isolated ambulatory hypertension, defined as an elevated
      ambulatory BP with normal office blood pressure, in a series of 1488 consecutive
      outpatients referred for routine clinical evaluation of suspected or established
      arterial hypertension. All patients underwent both office BP (OBP) measurement by
      a physician and 24-h ambulatory blood pressure monitoring (ABPM). Using OBP
      values (cutoff for diagnosis of hypertension >/=140/90 mmHg) and daytime ABPM
      (cutoff for diagnosis of hypertension >/=135/85 mmHg), patients were classified
      into eight subgroups. In the whole series we found that, independent of treatment
      status, the prevalence of isolated ambulatory hypertension exceeded 10%. More
      importantly, 45.3% of individuals who presented with normal OBP values, showed
      elevated BP at ABPM. Night-time BP, 24-h pulse pressure, and BP variability were
      significantly higher in isolated ambulatory hypertensives than in normotensive or
      in white-coat hypertensive individuals. Therefore, isolated ambulatory
      hypertension is characterized by a blood pressure profile that is similar to that
      observed in sustained hypertension. These findings suggest that isolated
      ambulatory hypertension is very common and probably the indications for ABPM
      should be more extensive in outpatients referred to hypertensive centre.

PMID- 15241443
TI  - The role of tetraploids in the sexual-asexual cycle in dandelions (Taraxacum).
AB  - Apomictic plants often produce pollen that can function in crosses with related
      sexuals. Moreover, facultative apomicts can produce some sexual offspring. In
      dandelions, Taraxacum, a sexual-asexual cycle between diploid sexuals and
      triploid apomicts, has been described, based on experimental crosses and
      population genetic studies. Little is known about the actual hybridization
      processes in nature. We therefore studied the sexual-asexual cycle in a mixed
      dandelion population in the Netherlands. In this population, the frequencies of
      sexual diploids and triploids were 0.31 and 0.68, respectively. In addition, less
      than 1% tetraploids were detected. Diploids were strict sexuals, triploids were
      obligate apomicts, but tetraploids were most often only partly apomictic, lacking
      certain elements of apomixis. Tetraploid seed fertility in the field was
      significantly lower than that of apomictic triploids. Field-pollinated sexual
      diploids produced on average less than 2% polyploid offspring, implying that the
      effect of hybridization in the 2x-3x cycle in Taraxacum will be low. Until now,
      2x-3x crosses were assumed to be the main pathway of new formation of triploid
      apomicts in the sexual-asexual cycle in Taraxacum. However, tetraploid pollen
      donors produced 28 times more triploid offspring in experimental crosses with
      diploid sexuals than triploid pollen donors. Rare tetraploids may therefore act
      as an important bridge in the formation of new triploid apomicts.

PMID- 15241444
TI  - Fitness and life-history traits of the two major mitochondrial DNA haplotypes of
      Drosophila subobscura.
AB  - Mitochondrial DNA restriction site analyses on natural populations of Drosophila
      subobscura have proved the existence of two common, coexisting haplotypes (I and
      II), as well as a set of less frequent ones derived from them. To explain this
      distribution, experiments to date point practically to all possible genetic
      mechanisms being involved in the changes of gene frequencies (cytonuclear
      coadaptation, direct natural selection on mtDNA and genetic drift). In an attempt
      to find differences that help to understand the dynamics of these haplotypes and
      to detect the effect of selection, we measured certain fitness components and
      life-history traits (egg-larva and larva-adult viabilities and developmental
      times, longevity, resistance to desiccation and optimal density) of the two main
      haplotypes I and II when maintained in laboratory population cages. As a general
      trend, haplotype II showed a higher net fitness than haplotype I, which explains
      the superiority of haplotype II over haplotype I in experimental populations but
      not their coexistence in nature, where additional factors must be considered.

PMID- 15241445
TI  - Host-associated genetic differentiation in Thrips tabaci (Insecta; Thysanoptera),
      as determined from mtDNA sequence data.
AB  - We tested for host-associated genetic differentiation in 22 populations of Thrips
      tabaci collected from tobacco and leek, respectively. Clustering analyses and
      haplotype networks based on sequence variation at a fragment of the mitochondrial
      cytochrome oxidase I gene yielded three major evolutionary lineages; two were
      clearly associated with leek and the third with tobacco. These genetic findings
      corroborated recent experimental observations on the heterogeneity of T. tabaci
      populations with regard to host-plant preference and their capacity to be vectors
      for tomato spotted wilt virus. Estimated divergence times suggested an ancient
      divergence of these lineages dating back to the Miocene 28-21 million years ago.
      F(ST) values between these lineages ranged between 0.824 and 0.954 (P<0.001 for
      all comparisons), and sequence divergences ranged between 4 and 11%. Given these
      findings and by the standards of genetic and ecological differentiation in other
      published species groups, T. tabaci must be considered a complex of cryptic
      (sub)species.

PMID- 15241446
TI  - Chromosome evolution in the erythrinid fish, Erythrinus erythrinus (Teleostei:
      Characiformes).
AB  - The genus Erythrinus belongs to the family Erythrinidae, a neotropical fish
      group. This genus contains only two described species, Erythrinus erythrinus
      being the most widely distributed in South America. Six samples of this species
      from five distinct Brazilian localities and one from Argentina were studied
      cytogenetically. Four groups were identified on the basis of their chromosomal
      features. Group A comprises three samples, all with 2n = 54 chromosomes, a very
      similar karyotypic structure, and the absence of chromosome differentiation
      between males and females. One sample bears up to four supernumerary
      microchromosomes, which look like 'double minute chromosomes' in appearance.
      Groups B-D comprise the three remaining samples, all sharing an
      X(1)X(1)X(2)X(2)/X(1)X(2)Y sex chromosome system. Group B shows 2n = 54/53
      chromosomes in females and males, respectively, and also shows up to three
      supernumerary microchromosomes. Groups C and D show 2n=52/51 chromosomes in
      females and males, respectively, but differ in the number of metacentric,
      subtelocentric, and acrocentric chromosomes. In these three groups (B-D), the Y
      is a metacentric chromosome clearly identified as the largest in the complement.
      The present results offer clear evidence that local samples of E. erythrinus
      retain exclusive and fixed chromosomal features, indicating that this species may
      represent a species complex.

PMID- 15241447
TI  - The role of swarming sites for maintaining gene flow in the brown long-eared bat
      (Plecotus auritus).
AB  - Bat-swarming sites where thousands of individuals meet in late summer were
      recently proposed as 'hot spots' for gene flow among populations. If, due to
      female philopatry, nursery colonies are genetically differentiated, and if males
      and females of different colonies meet at swarming sites, then we would expect
      lower differentiation of maternally inherited genetic markers among swarming
      sites and higher genetic diversity within. To test these predictions, we compared
      genetic variance from three swarming sites to 14 nursery colonies. We analysed
      biparentally (five nuclear and one sex-linked microsatellite loci) and maternally
      (mitochondrial D-loop, 550 bp) inherited molecular markers. Three mtDNA D-loop
      haplolineages that were strictly separated at nursery colonies were mixed at
      swarming sites. As predicted by the 'extra colony-mating hypothesis', genetic
      variance among swarming sites (V(ST)) for the D-loop drastically decreased
      compared to the nursery population genetic variance (V(PT)) (31 and 60%,
      respectively), and genetic diversity increased at swarming sites. Relatedness was
      significant at nursery colonies but not at swarming sites, and colony relatedness
      of juveniles to females was positive but not so to males. This suggests a
      breakdown of colony borders at swarming sites. Although there is behavioural and
      physiological evidence for sexual interaction at swarming sites, this does not
      explain why mating continues throughout the winter. We therefore propose that
      autumn roaming bats meet at swarming sites across colonies to start mating and,
      in addition, to renew information about suitable hibernacula.

PMID- 15241448
TI  - Allozyme variation and structure of the Canarian endemic palm tree Phoenix
      canariensis (Arecaceae): implications for conservation.
AB  - Electrophoretic analysis of 18 allozyme loci was used to estimate the levels and
      structuring of genetic variation within and among natural populations of the
      protected endemic palm species from the Canary Islands (Phoenix canariensis) to
      evaluate its genetic relationship with the widespread congener P. dactylifera,
      and to assess comparatively the genetic variation in the populations where the
      two species coexist with morphologically intermediate plants (mixed populations).
      Our survey revealed that the within-population component explains roughly 75% of
      the genetic variation levels detected in P. canariensis (A=1.59; P=41.8;
      He=0.158), which rank higher than those reported for other species of the
      Arecaceae. A Principal Component analysis (PCA) based on allele frequencies
      consistently separates populations of P. canariensis and P. dactylifera, and
      reveals a close genetic relationship between P. canariensis and the mixed
      populations. Reduced levels of genetic variation in P. canariensis with respect
      to P. dactylifera, the fact that the genetic makeup of the Canarian endemic (with
      no unique alleles) is a subset of that found in P. dactylifera, and the high
      genetic identity between both species strongly suggest that P. canariensis is
      recently derived from a common ancestor closely related to P. dactylifera.

PMID- 15241449
TI  - Douglas Scott Falconer (1913-2004).

PMID- 15241450
TI  - Recombination and clonal propagation in different populations of the lichen
      Lobaria pulmonaria.
AB  - Propagation, dispersal, and establishment are fundamental population processes,
      and are critical stages in the life cycle of an organism. In symbiotic organisms
      such as lichens, consisting of a fungus and a population of photobionts,
      reproduction is a complex process. Although many lichens are able to reproduce
      both sexually and asexually, the extent of vegetative propagation within local
      populations is unknown. We used six polymorphic microsatellite loci to
      investigate whether recombination is common in natural populations, and to assess
      if and how clonal reproduction influences the spatial genetic structure within
      populations of the epiphytic lichen species Lobaria pulmonaria. High genetic
      diversity within all 12 investigated populations and evidence of recombination,
      from various tests, indicated that L. pulmonaria is a predominantly outcrossing
      species. Nevertheless, clonality occurred in all populations, but the presence of
      recurring multilocus genotypes influenced the spatial genetic structure only
      within low-density populations. This could be interpreted as indicative of
      genetic bottlenecks owing to increased habitat loss and disturbance.
      Consequently, for a predominantly outcrossing lichen species, exogenous factors
      might be substantially altering population processes and hence genetic structure.

PMID- 15241451
TI  - Mitochondrial DNA and microsatellite analyses of the genetic status of the
      presumed subspecies Cervus elaphus montanus (Carpathian red deer).
AB  - The possibly distinct Carpathian red deer was compared genetically to other
      European populations. We screened 120 red deer specimens from Serbia, the
      Romanian lowland and the Romanian Carpathians for genetic variability using 582
      bp of the mitochondrial control region and nine polymorphic nuclear
      microsatellite loci. The study aimed at a population genetic characterization of
      the Carpathian red deer, which are often treated as a distinct subspecies (Cervus
      elaphus montanus). The genetic integrity of the Carpathian populations was
      confirmed through the haplotype distribution, private alleles and genetic
      distances. The Carpathian red deer are thus identified as one of the few
      remaining natural populations of this species, deserving special attention among
      game and conservation biologists. The history of the populations studied, in
      particular the introduction of Carpathian red deer into Romanian lowland areas in
      the 20th century, was reflected by the genetic data.

PMID- 15241452
TI  - Landscape genetics of alpine-snowbed plants: comparisons along geographic and
      snowmelt gradients.
AB  - The genetic structure of three snowbed-herb species (Peucedanum multivittatum,
      Veronica stelleri, and Gentiana nipponica) was analyzed using allozymes across
      nine populations arranged as a matrix of three snowmelt gradients x three
      geographic locations within 3 km in the Taisetsu Mountains, northern Japan.
      Phenologically asynchronous populations are packed within a local area in alpine
      snowbeds, because flowering season of alpine plants depends strongly on the
      timing of snowmelt. Moderate genetic differentiation was detected among local
      populations in every species (FST=0.03-0.07). There was a significant correlation
      between the geographic distance and genetic distance in the P. multivittatum
      populations, but not in the V. stelleri and G. nipponica populations. On the
      other hand, a significant correlation between the phenological distance caused by
      snowmelt timing and genetic distance was detected in the V. stelleri and G.
      nipponica populations, but not in the P. multivittatum populations. The snowmelt
      gradient or geographic separation influenced hierarchical genetic structure of
      these species moderately (FRT <0.04). Restriction of gene flow due to
      phenological separation and possible differential selection along the snowmelt
      gradient may produce genetic clines at microgeographic scale in these species.

PMID- 15241453
TI  - Genetic basis and fitness consequences of winglessness in the two-spot ladybird
      beetle, Adalia bipunctata.
AB  - The genetic basis and fitness consequences of winglessness were investigated in
      the two-spot ladybird beetle, Adalia bipunctata. By breeding lines from a
      wingless individual found at The Uithof, Utrecht in The Netherlands, the wingless
      condition was confirmed to be under the control of a major allele, recessive to
      the wild type. Wingless individuals, on average, had a longer developmental
      period, a lower egg production and a shorter lifespan than the wild type with
      wings, suggesting that the expression of the wingless allele has functionally
      interrelated gene actions involving a wide range of fitness components. While the
      wingless allele influences various traits, significant among-family variation in
      the degree of winglessness suggests that its phenotypic expression is also
      dependent on the genetic background and modifier loci. Furthermore, there was a
      consistent pattern of correlation between the degree of winglessness and life
      history traits; the most extreme wingless individuals showed the lowest fitness
      while those with more fully developed wings tended to have the highest fitness.
      This correlation suggests that the modifier genes influence both wing formation
      and fitness components. The significance of such epistatic effects to the
      evolution of flightlessness in insects is discussed.

PMID- 15241454
TI  - Autosomes behaving badly.

PMID- 15241455
TI  - Genetic introgression between wild and stocked salmonids and the prospects for
      using molecular markers in population rehabilitation: the case of the Adriatic
      grayling (Thymallus thymallus L. 1785).
AB  - In the north Adriatic basin, a morphologically and genetically distinct lineage
      of grayling is found, designated as the Adriatic grayling. In Slovenia, the
      Adriatic grayling is restricted to the Soca river system, where it is critically
      endangered. The most pertinent threat is stocking with non-native, highly
      divergent Sava (Danubian) drainage stock, and this activity has been going on for
      more than four decades. The present study was designed to characterise the
      genetic structure of the Adriatic grayling in Slovenia, with particular emphasis
      on estimating the degree of introgression with non-indigenous stocked grayling.
      We analysed polymorphism at 154 microsatellite loci in samples representing
      grayling from the Adriatic and Danubian drainage stock. A relatively high number
      (12) of alleles, diagnostic for the Adriatic grayling, were identified. However,
      a correspondence analysis based on individual multilocus genotypes also revealed
      that there is no distinctive Adriatic group but rather a dispersed multitude of
      individuals that cannot be unambiguously distinguished from the more homogenous
      Danubian population. A Bayesian analysis of individual admixture coefficients
      confirmed this pattern and revealed extensive introgression between the Adriatic
      grayling and stocked grayling of Danubian origin. Average individual admixture
      coefficients showed that only between 50 and 60% of the original gene pools
      remained, and only few non-introgressed indigenous individuals could be
      identified. Microsatellite-based individual admixture analysis appear to be an
      important tool for identifying remaining non-introgressed indigenous individuals
      that could be used for restoring the original populations.

PMID- 15241456
TI  - Low diversity in the major histocompatibility complex class II DRB1 gene of the
      Spanish ibex, Capra pyrenaica.
AB  - During the last two centuries, the Spanish ibex (Capra pyrenaica) has shown a
      significant demographic decline as a result of the progressive destruction of its
      natural habitat, disease epidemics, and uncontrolled hunting. Partial sequencing
      of the class II MHC DRB1 gene revealed that the Spanish ibex has remarkably low
      levels of genetic variation at this locus, with only six different DRB1 alleles
      and an observed heterozygosity of 0.429-0.579. The rates of nonsynonymous vs
      synonymous substitutions were significantly different in the peptide-binding
      region (dN/dS=5.347, P=0.002), a feature that indicates that the DRB1 gene is
      under positive selection. A phylogenetic analysis of the Spanish ibex and a set
      of domestic goat DRB1 alleles revealed that the reported sequences represent four
      major allelic lineages. The limited allelic repertoire of the DRB1 gene in the
      Spanish ibex is likely the direct result of the recent history of population
      bottlenecks and marked demographic decline of this species. A genetic survey of
      13 microsatellite loci was consistent with this idea. The Spanish ibex subspecies
      C. p. hispanica and C. p. victoriae consistently showed considerably lower levels
      of microsatellite heterozygosity (Ho=0.184-0.231) and allelic diversity (mean
      number of alleles per locus=2-2.4) than those reported in other wild ruminants.
      This study demonstrates the significance of both natural selection and the
      demographic history of populations in determining patterns of genetic variation
      at MHC loci. In addition, our results emphasize the importance of locally adapted
      populations for the preservation of genetic diversity.

PMID- 15241457
TI  - Heterosis and epistasis for teat number and fluctuating asymmetry in crosses
      between Jiaxing and Iberian pigs.
AB  - In the framework of Wright's view of evolution, long-separate breeds of domestic
      animals could establish different adaptive epistatic genetic complexes that could
      be destroyed in crossbred animals by recombination. The objective of this study
      was to evaluate heterosis and recombination effects in a crossing experiment
      involving two distinct European and Asian breeds (Iberian and Jiaxing) in the F1
      and two successive backcrosses to the Iberian line. Teat number (TN) was recorded
      in the right and left sides of piglets and analysed by fitting a mixed linear
      model including the Dickerson's crossbreeding parameters. TN in pigs is a
      discontinuous and often canalised trait presenting bilateral symmetry. The minor
      differences between sides make this trait a good candidate to evaluate
      fluctuating asymmetry (FA) and developmental instability. For TN, the posterior
      means and standard deviations (SD) of the heritability and of the relative
      contribution of common litter environmental effect to variance were 0.248 (0.028)
      and 0.057 (0.019), respectively. The respective values of the difference between
      breeds, heterosis and recombination effect were 9.990 (0.411), -0.506 (0.196) and
      0.684 (0.232). For FA, the posterior means and SDs of the heritability and of the
      relative contribution of common litter environmental effect to variance were
      0.023 (0.005) and 0.014 (0.005), respectively. Another significant genetic effect
      was a recombination effect of 0.773 (0.117). These results confirm that the
      rupture by recombination of coadapted genomes decreases developmental stability
      in domestic pigs.

PMID- 15241458
TI  - Heritabilities and additive genetic variances of the activities of some enzymes
      in Drosophila melanogaster populations living in different habitats.
AB  - Drosophila melanogaster samples were collected from a large population in two
      habitats: farmyards and distilleries. Samples were taken from two villages in
      each habitat. Three isofemale lines were established from all four samples and
      full-sib crosses were set in each isofemale line. Activities of four enzymes
      (ADH, alpha GPDH, IDH and 6PGDH) were measured in the offspring of each cross on
      starch gel after electrophoresis. Broad sense heritabilities and additive genetic
      variances were estimated in all four samples. Most of the activity variation was
      observed within the isofemale lines. The isofemale lines tended to be more
      different in the distilleries than in the farmyards. There was no significant
      difference in the average activities between the two habitats for any of the
      enzymes investigated. The additive genetic variance of the enzyme activities did
      not exhibit a consistent habitat pattern. In the farmyard habitat, we detected a
      higher activity variation in Tiszafured than in the other village. Strong
      correlation was observed among the activities of the enzymes investigated.
      Correlation coefficients indicated higher level of correlation in the samples
      collected in Tiszafured than in those originating from Tiszaszolos. The
      heritability values were rather high and they had a considerable variation both
      between the habitats and across the enzymes.

PMID- 15241459
TI  - Small-scale clinal variation, genetic diversity and environmental heterogeneity
      in the marine gobies Pomatoschistus minutus and P. lozanoi (Gobiidae, Teleostei).
AB  - Genetic variation was assayed at 14 allozyme loci in estuarine, coastal and
      offshore samples of lozano's goby, Pomatoschistus lozanoi and the sand goby, P.
      minutus. Samples were taken from locations on the Belgian Continental Shelf and
      in the Schelde estuary with a range of environmental heterogeneity. We evaluate
      whether any differences in (1) the degree of genetic variation and (2) allele
      frequencies at the various loci exist within samples occurring in various
      habitats on the BCS and in the Schelde estuary. No significant differences in
      levels of genetic diversity were recorded between estuarine, coastal and offshore
      samples in either species. A temporally stable clinal gradient in allele
      frequencies at the two-allele locus GPI-A(*) was observed in P. lozanoi,
      differentiating the samples in an estuarine, coastal and offshore group. We
      suggest that these differences might be maintained by balancing selection at
      locus GPI-A(*).

PMID- 15241460
TI  - Simulations of human colonization history.

PMID- 15241461
TI  - Mitochondrial DNA signatures of restricted gene flow within divergent lineages of
      an atyid shrimp (Paratya australiensis).
AB  - We measured spatial genetic structure within three previously described
      mitochondrial lineages of the atyid shrimp, Paratya australiensis, occurring in
      upland streams of two major catchments within the Sydney Water Supply Catchment,
      New South Wales, Australia. In all three lineages, there was significant spatial
      structuring of genetic variation between catchments. In two lineages, recurrent
      but restricted maternal gene flow has apparently predominated in shaping within
      catchment genetic structure, although this framework may be overlaid with
      episodic contiguous/long-distance expansion events. In the third lineage, there
      was no evidence of spatial genetic structuring within one of the catchments,
      because one haplotype was both common and widespread throughout the sampled area.
      High-frequency haplotypes were also shared among subcatchments in the other two
      lineages, and we discuss both historical and contemporary processes that may have
      left these genetic signatures. Our results are generally concordant with previous
      reports of significant population structuring in P. australiensis, occurring in
      upland river reaches elsewhere in eastern Australia. We propose that restricted
      dispersal and gene flow among upland populations of P. australiensis is linked to
      dramatic architectural structuring within and among mountain streams.

PMID- 15241462
TI  - Mixed mating in natural populations of the chestnut blight fungus, Cryphonectria
      parasitica.
AB  - As in plants, fungi exhibit wide variation in reproductive strategies and mating
      systems. Although most sexually reproducing fungi are either predominantly
      outcrossing or predominantly selfing, there are some notable exceptions. The
      haploid, ascomycete chestnut blight pathogen, Cryphonectria parasitica, has
      previously been shown to have a mixed mating system in one population in USA. In
      this report, we show that both selfing and outcrossing occur in 10 additional
      populations of C. parasitica sampled from Japan, Italy, Switzerland and USA.
      Progeny arrays from each population were assayed for segregation at vegetative
      incompatibility (vic) and DNA fingerprinting loci. Outcrossing rates (t(m)) were
      estimated as the proportion of progeny arrays showing segregation at one or more
      loci, corrected by the probability of nondetection of outcrossing (alpha).
      Estimates of t(m) varied from 0.74 to 0.97, with the lowest rates consistently
      detected in USA populations (0.74-0.78). Five populations (four in USA and one in
      Italy) had t(m) significantly less than 1, supporting the conclusion that these
      populations exhibit mixed mating. The underlying causes of variation in
      outcrossing rates among populations of C. parasitica are not known, but we
      speculate that--as in plants--outcrossing is a function of ecological,
      demographic and genetic factors.

PMID- 15241463
TI  - Uniformity of the nuclear and chloroplast genomes of Spartina maritima (Poaceae),
      a salt-marsh species in decline along the Western European Coast.
AB  - Spartina maritima is a salt-marsh species from European and African Atlantic
      coasts. In the northern range of the species (including north-west France), a
      rapid decline of the populations has been observed during the 20th century. In
      this paper, the molecular diversity of 10 populations of S. maritima from France
      has been investigated using nuclear and chloroplast DNA markers: inter-simple
      sequence polymorphism (ISSR), randomly amplified polymorphic DNA (RAPD), inter
      retrotransposon amplified polymorphism (IRAP), and PCR-RFLP of a 5 kb long
      portion of chloroplast DNA. The results reveal an extremely low level of genetic
      variation in this species: only one nuclear marker (out of 98) was polymorphic,
      with the presence of two genotypes randomly distributed among the populations.
      The lack of genetic diversity is interpreted in light of the almost exclusive
      vegetative propagation of the species in its northern range, the colonization
      history of the populations, and the origin of S. maritima (2n = 60) in the
      hexaploid lineage of the genus and in the context of the management of S.
      maritima populations.

PMID- 15241464
TI  - A multilocus microsatellite phylogeny of the Drosophila virilis group.
AB  - We used a set of 48 polymorphic microsatellites derived from Drosophila virilis
      to infer phylogenetic relationships in the D. virilis clade. Consistent with
      previous studies, D. virilis and D. lummei were the most basal species of the
      group. Within the D. montana phylad, the phylogenetic relationship could not be
      resolved. Special attention was given to the differentiation between D. americana
      texana, D. americana americana and D. novamexicana. Significant differences
      between these three groups were detected by F(ST) analyses. Similarly, a model
      based clustering method for multilocus genotype data also provided strong support
      for the presence of three differentiated groups. This genome-wide differentiation
      between D. americana texana and D. americana americana contrasts with previous
      analyses based on DNA sequence data.

PMID- 15241465
TI  - Clonal diversity in the ancient asexual ostracod Darwinula stevensoni assessed by
      RAPD-PCR.
AB  - As Darwinulidae (Ostracoda) are considered to be ancient asexuals with a wide
      geographical and ecological distribution, they are expected to have accumulated
      mutations during a long timeframe. However, previous studies on genetic
      variability suggested a low genetic divergence within the darwinulid species
      Darwinula stevensoni. Here, overall genotopic diversity of D. stevensoni is
      estimated with the Random Amplified Polymorphic DNA (RAPD) technique. Using six
      primers revealing 47 consistently scorable polymorphic loci, substantial clonal
      diversity within this species is detected. Five of the seven surveyed populations
      are multiclonal. Moreover, the seven populations have a different clonal
      composition with almost all of the observed clonal genotypes being restricted to
      single populations, indicating the absence of a single widespread 'clone'. The
      observed clonal diversity seems to refute the existence of a widespread general
      purpose genotype for D. stevensoni. However, in light of previously detected
      uniformity at functional loci, we reconsider the definition of a GPG. We suggest
      that it need not imply a genome-wide fixed genotype, but rather consists of a set
      of ecologically relevant genes.

PMID- 15241466
TI  - Evidence for gene flow and local clonal selection in field populations of the
      grain aphid (Sitobion avenae) in Britain revealed using microsatellites.
AB  - Samples of the grain aphid, Sitobion avenae (F.), a major European pest of
      cereals, were collected in June and July 1997 from fields sown with winter wheat
      in a rough transect south-west of Rothamsted, UK. These aphids were genotyped at
      four microsatellite loci known from previous studies to be highly polymorphic.
      Allelic frequencies were similar between samples collected in the fields and in
      the 12.2 m high suction trap at Rothamsted, and there were many widespread
      genotypes (clones), providing evidence that the species is highly migratory.
      However, field samples were found to display a high level of genotypic
      heterogeneity (= variable clonal composition), most probably the result of clonal
      selection. The suction trap genotypes sample were slightly different from the
      field samples, indicative of the inclusion of genotypes from plant hosts (cereals
      and grasses, Poaceae) other than winter wheat and/or genotype-biased emigration
      from the field. The relevance of these data to modelling of aphid outbreaks is
      briefly discussed.

PMID- 15241467
TI  - Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene
      duplication is more prevalent in rheumatoid arthritis.
AB  - The death receptor 3 (DR3) gene is a member of the apoptosis-inducing Fas gene
      family. In the current study, fluorescence in situ hybridization (FISH) and Fiber
      FISH revealed the existence of a second DR3 gene approximately 200 kb upstream of
      the original DR3 gene. The existence of the duplicated DR3 gene was confirmed by
      sequencing the corresponding human artificial chromosome clones as well as with
      quantitative PCR that measured the ratio of the DR3 gene mutation (Rm), intrinsic
      to rheumatoid arthritis (RA) patients, by simultaneous amplification of the
      normal and mutated DR3 sequences. The DR3 gene duplication measured by FISH was
      found to be more frequent in patients with RA as compared to healthy individuals.
      We therefore surmise that the human DR3 gene can be duplicated and that this gene
      duplication is more prevalent in patients with RA.

PMID- 15241468
TI  - Myc-induced proliferation and transformation require Akt-mediated phosphorylation
      of FoxO proteins.
AB  - Myc synergizes with Ras and PI3-kinase in cell transformation, yet the molecular
      basis for this behavior is poorly understood. We now show that Myc recruits
      TFIIH, P-TEFb and Mediator to the cyclin D2 and other target promoters, while the
      PI3-kinase pathway controls formation of the pre-initiation complex and loading
      of RNA polymerase II. The PI3-kinase pathway involves Akt-mediated
      phosphorylation of FoxO transcription factors. In a nonphosphorylated state, FoxO
      factors inhibit induction of multiple Myc target genes, Myc-induced cell
      proliferation and transformation by Myc and Ras. Abrogation of FoxO function
      enables Myc to activate target genes in the absence of PI3-kinase activity and to
      induce foci formation in primary cells in the absence of oncogenic Ras. We
      suggest that the cooperativity between Myc and Ras is at least in part due to the
      fact that Myc and FoxO proteins control distinct steps in the activation of an
      overlapping set of critical target genes.

PMID- 15241469
TI  - A soluble SNARE drives rapid docking, bypassing ATP and Sec17/18p for vacuole
      fusion.
AB  - Membrane fusion requires priming, the disassembly of cis-SNARE complexes by the
      ATP-driven chaperones Sec18/17p. Yeast vacuole priming releases Vam7p, a soluble
      SNARE. Vam7p reassociation during docking allows trans-SNARE pairing and fusion.
      We now report that recombinant Vam7p (rVam7p) enters into complex with other
      SNAREs in vitro and bypasses the need for Sec17p, Sec18p, and ATP. Thus, the sole
      essential function of vacuole priming in vitro is the release of Vam7p from cis
      SNARE complexes. In 'bypass fusion', without ATP but with added rVam7p, there are
      sufficient unpaired vacuolar SNAREs Vam3p, Vti1p, and Nyv1p to interact with
      Vam7p and support fusion. However, active SNARE proteins are not sufficient for
      bypass fusion. rVam7p does not bypass requirements for Rho GTPases,Vps33p,
      Vps39p, Vps41p, calmodulin, specific lipids, or Vph1p, a subunit of the V-ATPase.
      With excess rVam7p, reduced levels of PI(3)P or functional Ypt7p suffice for
      bypass fusion. High concentrations of rVam7p allow the R-SNARE Ykt6p to
      substitute for Nyv1p for fusion; this functional redundancy among vacuole SNAREs
      may explain why nyv1delta strains lack the vacuole fragmentation seen with
      mutants in other fusion catalysts.

PMID- 15241470
TI  - Arabidopsis CYP86A2 represses Pseudomonas syringae type III genes and is required
      for cuticle development.
AB  - Pseudomonas syringae relies on type III secretion system to deliver effector
      proteins into the host cell for parasitism. Type III genes are induced in planta,
      but host factors affecting the induction are poorly understood. Here we report on
      the identification of an Arabidopsis mutant, att1 (for aberrant induction of type
      three genes), that greatly enhances the expression of bacterial type III genes
      avrPto and hrpL. att1 plants display enhanced disease severity to a virulent
      strain of P. syringae, suggesting a role of ATT1 in disease resistance. ATT1
      encodes CYP86A2, a cytochrome P450 monooxygenase catalyzing fatty acid oxidation.
      The cutin content is reduced to 30% in att1, indicating that CYP86A2 plays a
      major role in the biosynthesis of extracellular lipids. att1 has a loose cuticle
      membrane ultrastructure and shows increased permeability to water vapor,
      demonstrating the importance of the cuticle membrane in controlling water loss.
      The enhanced avrPto-luc expression is specific to att1, but not another cuticle
      mutant, wax2. The results suggest that certain cutin-related fatty acids
      synthesized by CYP86A2 may repress bacterial type III gene expression in the
      intercellular spaces.

PMID- 15241471
TI  - Structural basis for L27 domain-mediated assembly of signaling and cell polarity
      complexes.
AB  - L27 is a protein-binding domain that can assemble essential proteins for
      signaling and cell polarity into complexes by interacting in a heterodimeric
      manner. One of these protein complexes is the PATJ/PALS1/Crumbs tripartite
      complex, which is crucial for the establishment and maintenance of cell polarity.
      To reveal the structural basis underlining the obligate heterodimerization, we
      have determined the crystal structure of the PALS1-L27N/PATJ-L27 heterodimer
      complex. Each L27 domain is composed of three helices. The two L27 domains
      heterodimerize by building a compact structure consisting of a four-helix bundle
      formed by the first two helices of each L27 domain and one coiled-coil formed by
      the third helix of each domain. The large hydrophobic packing interactions
      contributed by all the helices of both L27 domains predominantly drive the
      heterodimer formation, which is likely to be a general feature of L27 domains.
      Combined with mutational studies, we can begin to understand the structural basis
      for the specificity of L27 binding pairs. Our results provide unique insights
      into L27 domain heterodimer complex, which is critical for cell polarization.

PMID- 15241472
TI  - A class of plant glycosyltransferases involved in cellular homeostasis.
AB  - Many small lipophilic compounds in living cells can be modified by glycosylation.
      These processes can regulate the bioactivity of the compounds, their
      intracellular location and their metabolism. The glycosyltransferases involved in
      biotransformations of small molecules have been grouped into Family 1 of the 69
      families that are classified on the basis of substrate recognition and sequence
      relatedness. In plants, these transfer reactions generally use UDP-glucose with
      acceptors that include hormones such as auxins and cytokinins, secondary
      metabolites such as flavonoids, and foreign compounds including herbicides and
      pesticides. In mammalian organisms, UDP-glucuronic acid is typically used in the
      transfer reactions to endogenous acceptors, such as steroid and thyroid hormones,
      bile acids and retinoids, and to xenobiotics, including nonsteroidal anti
      inflammatory drugs and dietary metabolites. There is widespread interest in this
      class of enzyme since they are known to function both in the regulation of
      cellular homeostasis and in detoxification pathways. This review outlines current
      knowledge of these glycosyltransferases drawing on information gained from
      studies of plant and mammalian enzymes.

PMID- 15241473
TI  - GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for
      glucose transport stimulation.
AB  - G protein-coupled receptor kinases (GRKs) represent a class of proteins that
      classically phosphorylate agonist-activated G protein-coupled receptors, leading
      to uncoupling of the receptor from further G protein activation. Recently, we
      have reported that the heterotrimeric G protein alpha-subunit, Galphaq/11, can
      mediate insulin-stimulated glucose transport. GRK2 contains a regulator of G
      protein signaling (RGS) domain with specificity for Galphaq/11. Therefore, we
      postulated that GRK2 could be an inhibitor of the insulin signaling cascade
      leading to glucose transport in 3T3-L1 adipocytes. In this study, we demonstrate
      that microinjection of anti-GRK2 antibody or siRNA against GRK2 increased insulin
      stimulated insulin-responsive glucose transporter 4 (GLUT4) translocation, while
      adenovirus-mediated overexpression of wild-type or kinase-deficient GRK2
      inhibited insulin-stimulated GLUT4 translocation as well as 2-deoxyglucose
      uptake. Importantly, a mutant GRK2 lacking the RGS domain was without effect.
      Taken together, these results indicate that through its RGS domain endogenous
      GRK2 functions as a negative regulator of insulin-stimulated glucose transport by
      interfering with Galphaq/11 signaling to GLUT4 translocation. Furthermore,
      inhibitors of GRK2 can lead to enhanced insulin sensitivity.

PMID- 15241474
TI  - Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a
      single polypeptide.
AB  - Proteins belonging to the highly conserved RecQ helicase family are essential for
      the maintenance of genomic stability. Here, we describe the biochemical
      properties of the human RECQ5beta protein. Like BLM and WRN, RECQ5beta is an ATP
      dependent 3'-5' DNA helicase that can promote migration of Holliday junctions.
      However, RECQ5beta required the single-stranded DNA-binding protein RPA in order
      to mediate the efficient unwinding of oligonucleotide-based substrates.
      Surprisingly, we found that RECQ5beta possesses an intrinsic DNA strand-annealing
      activity that is inhibited by RPA. Analysis of deletion variants of RECQ5beta
      revealed that the DNA helicase activity resides in the conserved N-terminal
      portion of the protein, whereas strand annealing is mediated by the unique C
      terminal domain. Moreover, the strand-annealing activity of RECQ5beta was
      strongly inhibited by ATPgammaS, a poorly hydrolyzable analog of ATP. This effect
      was alleviated by mutations in the ATP-binding motif of RECQ5beta, indicating
      that the ATP-bound form of the protein cannot promote strand annealing. This is
      the first demonstration of a DNA helicase with an intrinsic DNA strand-annealing
      function residing in a separate domain.

PMID- 15241476
TI  - Preferential cleavage of chromatin-bound cohesin after targeted phosphorylation
      by Polo-like kinase.
AB  - The final irreversible step in the duplication and dissemination of eukaryotic
      genomes takes place when sister chromatid pairs split and separate in anaphase.
      This is triggered by the protease separase that cleaves the Scc1 subunit of
      'cohesin', the protein complex responsible for holding sister chromatids together
      in metaphase. Only part of cellular cohesin is bound to chromosomes in metaphase,
      and it is unclear whether and how separase specifically targets this fraction for
      cleavage. We established an assay to compare cleavage of chromatin-bound versus
      soluble budding yeast cohesin. Scc1 in chromosomal cohesin is significantly
      preferred by separase over Scc1 in soluble cohesin. The difference is most likely
      due to preferential phosphorylation of chromatin-bound Scc1 by Polo-like kinase.
      Site-directed mutagenesis of 10 Polo phosphorylation sites in Scc1 slowed
      cleavage of chromatin-bound cohesin, and hyperphosphorylation of soluble Scc1 by
      Polo overexpression accelerated its cleavage to levels of chromosomal cohesin.
      Polo is bound to chromosomes independently of cohesin's presence, providing a
      possible explanation for chromosome-specific cohesin modification and targeting
      of separase cleavage.

PMID- 15241475
TI  - Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to
      death ligand TRAIL.
AB  - Retinoids and interferons are signaling molecules with pronounced anticancer
      activity. We show that in both acute promyelocytic leukemia and breast cancer
      cells the retinoic acid (RA) and interferon signaling pathways converge on the
      promoter of the tumoricidal death ligand TRAIL. Promoter mapping, chromatin
      immunoprecipitation and RNA interference reveal that retinoid-induced interferon
      regulatory factor-1 (IRF-1), a tumor suppressor, is critically required for TRAIL
      induction by both RA and IFNgamma. Exposure of breast cancer cells to both
      antitumor agents results in enhanced TRAIL promoter occupancy by IRF-1 and
      coactivator recruitment, leading to strong histone acetylation and synergistic
      induction of TRAIL expression. In coculture experiments, pre-exposure of breast
      cancer cells to RA and IFNgamma induced a dramatic TRAIL-dependent apoptosis in
      heterologous cancer cells in a paracrine mode of action, while normal cells were
      not affected. Our results identify a novel TRAIL-mediated tumor suppressor
      activity of IRF-1 and suggest a mechanistic basis for the synergistic antitumor
      activities of certain retinoids and interferons. These data argue for combination
      therapies that activate the TRAIL pathway to eradicate tumor cells.

PMID- 15241477
TI  - Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the
      spindle checkpoint.
AB  - The spindle checkpoint inhibits anaphase until all kinetochores have attached
      properly to spindle microtubules. The protein kinase Bub1 is an essential
      checkpoint component that resides at kinetochores during mitosis. It is shown
      herein that Xenopus Bub1 becomes hyperphosphorylated and the kinase is activated
      on unattached chromosomes. MAP kinase (MAPK) contributes to this phosphorylation,
      as inhibiting MAPK or altering MAPK consensus sites in Bub1 to alanine or valine
      (Bub1(5AV)) abolishes the phosphorylation and activation on chromosomes. Both
      Bub1 and Bub1(5AV) support the checkpoint under an optimal condition for spindle
      checkpoint activation. However, Bub1, but not Bub1(5AV), supports the checkpoint
      at a relatively low concentration of nuclei or the microtubule inhibitor
      nocodazole. Similar to Bub1(5AV), Bub1 without the kinase domain (Bub1(deltaKD))
      is also partially compromised in its checkpoint function and in its ability to
      recruit other checkpoint proteins to kinetochores. This study suggests that
      activation of Bub1 at kinetochores enhances the efficiency of the spindle
      checkpoint and is probably important in maintaining the checkpoint toward late
      prometaphase when the cell contains only a few or a single unattached
      kinetochore.

PMID- 15241479
TI  - A double cryptic chromosome imbalance is an important factor to explain
      phenotypic variability in Wolf-Hirschhorn syndrome.
AB  - A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo
      microdeletion was referred because of genotype-phenotype inconsistencies, first
      explained as phenotypic variability of the WHS. The actual deletion size was
      found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the
      last one, leading us to hypothesize the presence of an extrachromosome segment on
      the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting
      from an unbalanced de novo translocation was, in fact, detected in four patients
      and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8)
      translocations were maternal in origin, the rec(4p;4q) was paternal. With the
      purpose of verifying frequency and specificity of this phenomenon, we
      investigated yet another group of 20 WHS patients with de novo large deletions (n
      = 13) or microdeletions (n = 7) and with apparently straightforward genotype
      phenotype correlations. The rearrangement was paternal in origin, and occurred as
      a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted
      chromosome 4 was maternally derived and consisted of a der(4)(4qter -->
      4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo
      WHS-associated rearrangements were maternal in origin and 80% (20/25) were
      paternal. All the maternally derived rearrangements were de novo unbalanced
      t(4;8) translocations and showed specific clinical phenotypes. Paternally derived
      rearrangements were usually isolated deletions. It can be inferred that a double,
      cryptic chromosome imbalance is an important factor for phenotypic variability in
      WHS. It acts either by masking the actual deletion size or by doubling a
      quantitative change of the genome.

PMID- 15241478
TI  - The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation.
AB  - Schwann cells are a regenerative cell type. Following nerve injury, a
      differentiated myelinating Schwann cell can dedifferentiate and regain the
      potential to proliferate. These cells then redifferentiate during the repair
      process. This behaviour is important for successful axonal repair, but the
      signalling pathways mediating the switch between the two differentiation states
      remain unclear. Sustained activation of the Ras/Raf/ERK cascade in primary cells
      results in a cell cycle arrest and has been implicated in the differentiation of
      certain cell types, in many cases acting to promote differentiation. We therefore
      investigated its effects on the differentiation state of Schwann cells.
      Surprisingly, we found that Ras/Raf/ERK signalling drives the dedifferentiation
      of Schwann cells even in the presence of normal axonal signalling. Furthermore,
      nerve wounding in vivo results in sustained ERK signalling in associated Schwann
      cells. Elevated Ras signalling is thought to be important in the development of
      Schwann cell-derived tumours in neurofibromatosis type 1 patients. Our results
      suggest that the effects of Ras signalling on the differentiation state of
      Schwann cells may be important in the pathogenesis of these tumours.

PMID- 15241480
TI  - 1024C> T (R342X) is a recurrent PHF6 mutation also found in the original Borjeson
      Forssman-Lehmann syndrome family.

PMID- 15241481
TI  - RNAi of COL1A1 in mesenchymal progenitor cells.
AB  - Given that mutant COL1A1 is known to cause Osteogenesis Imperfecta (OI), tools to
      modulate COL1A1 expression are likely to be of significant therapeutic value. In
      this context, we have evaluated RNA interference (RNAi) as a means to
      downregulate COL1A1 expression in Cos-7 cells and in human mesenchymal progenitor
      stem cells (MPCs), the latter cells giving rise to bone and therefore
      representing a target cell type for collagen-related disorders. In addition,
      allele-specificity, a key factor to the success of RNAi-based suppression, was
      explored with a view to developing a mutation-independent RNAi-based therapeutic
      for OI by targeting an intragenic SNP within transcripts derived from the COL1A1
      gene. Preferential suppression of individual polymorphic alleles that differed by
      a single nucleotide was observed.

PMID- 15241482
TI  - Paraoxonase 1 polymorphisms and survival.
AB  - The antioxidant enzyme paraoxonase 1 (PON1) has previously been suggested to
      confer protection against coronary heart disease (CHD), one of the main causes of
      death in the Western world. Two coding polymorphisms, 55M/L and 192Q/R, and a
      promoter variant, -107C/T, has been extensively studied with respect to
      susceptibility to CHD. In this study, we have investigated the impact of these
      three polymorphisms on mortality using a sample of 1932 Danish individuals aged
      47-93 years, previously used in gene-longevity studies. A cross-sectional study
      comparing the genotype distribution of the three polymorphisms separately as well
      as the haplotype distribution in different age groups did not reveal any
      difference. However, a longitudinal follow-up study on survival in the same
      sample indicated that 192RR homozygotes have a poorer survival compared to QQ
      homozygotes (hazard rate: 1.38, P = 0.04). We hereafter used an independent
      sample of 541 Danish individuals from the oldest cohort and confirmed the initial
      findings (hazard rate: 1.38, P = 0.09). In both samples, the effect was most
      pronounced in women. Using self-reported data on ischemic heart disease to
      evaluate the impact of the PON 192Q/R polymorphism on susceptibility to CHD, we
      found only a nonsignificant trend of 192RR homozygosity in women being a risk
      factor. Our results thus indicates that PON1 192RR homozygosity is associated
      with increased mortality in women in the second half of life and that this
      increased mortality is possibly related to CHD severity and survival after CHD
      rather than susceptibility to development of CHD.

PMID- 15241483
TI  - Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha
      hydroxylase gene on serum lipid levels in normolipidaemic and
      hypertriglyceridaemic individuals.
AB  - The rate-limiting enzyme in the conversion of cholesterol into bile acids is
      cholesterol 7alpha-hydroxylase (CYP7A1). An A to C substitution 278 bp upstream
      in the promoter of the CYP7A1 gene was found to be associated with variations in
      serum lipid levels in normolipidaemic populations. In the present study, we
      investigated the involvement of this polymorphism in four different lipid
      disorders: hypertriglyceridaemia (HTG), combined hyperlipidaemia (CH), familial
      dysbetalipoproteinaemia (FD) and familial hypercholesterolaemia (FH). In a
      normolipidaemic male population, homozygous for the apoE3 isoform, an association
      was found between the AA genotype and higher levels of serum triglycerides (AA:
      +34%, P = 0.036). In HTG patients, the AA genotype was associated with
      significantly higher concentrations of total cholesterol (+23%, P = 0.005). There
      was a tendency towards increased levels of serum triglycerides (+39%, P = 0.06),
      VLDL-triglycerides (+48%, P = 0.053) and VLDL-cholesterol (+35%, P = 0.059). No
      significant associations were found between serum lipid levels and the CYP7A1
      polymorphism in patients with CH, FD and FH. Our results show that the A-278C
      polymorphism in the CYP7A1 gene has an effect on triglyceride levels in
      normolipidaemic males and on cholesterol levels in patients with
      hypertriglyceridaemia..

PMID- 15241484
TI  - Effect of genetic variation in the human S-adenosylhomocysteine hydrolase gene on
      total homocysteine concentrations and risk of recurrent venous thrombosis.
AB  - Hyperhomocysteinemia is an independent and graded risk factor for arterial
      vascular disease and venous thrombosis. It is still debated via which mechanism
      homocysteine (Hcy) causes vascular disease. S-adenosylhomocysteine hydrolase
      (AHCY) catalyses the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to
      Hcy. As an increase in AdoHcy, a strong inhibitor of many methyltransferases, is
      observed in hyperhomocysteinemic individuals, AdoHcy may play a role in the
      development of cardiovascular diseases by inhibiting transmethylation reactions.
      We sequenced the entire coding region and parts of the untranslated regions
      (UTRs) of the AHCY gene of 20 patients with recurrent venous thrombosis in order
      to identify genetic variation within this gene. We identified three sequence
      variants in the AHCY gene: a C > T transition in the 5' UTR (-34 bp C > T), a
      missense mutation in exon 2, which mandates an amino-acid conversion at codon 38
      (112 C > T; Arg38Trp) and a silent mutation in exon 4 (390 C > T; Asp130Asp). We
      studied the effect of the first two variants on total plasma Hcy and venous
      thrombosis risk in a case-control study on recurrent venous thrombosis. The two
      polymorphisms under study seem to have no evident effect on tHcy. The adjusted
      relative risk of venous thrombosis associated with the 112CT genotype compared
      with 112CC individuals was 1.27 (95% CI 0.55-2.94), whereas the -34CT genotype
      confers a risk of 1.25 (95% CI 0.44-3.52) compared with the wild-type genotype at
      this locus. However, the wide confidence intervals do not allow firm conclusions
      to be drawn.

PMID- 15241485
TI  - Cox proportional hazards survival regression in haplotype-based association
      analysis using the Stochastic-EM algorithm.
AB  - It is now widely recognized that haplotype information inferred from genotypes
      can be of great interest to better characterize the role of a candidate gene in
      the etiology of a complex trait in the context of association studies. Several
      works have recently advocated the simultaneous estimation of haplotype
      frequencies and haplotype effects in order to get a better efficiency in
      parameter estimation. Most of the available models can deal with a binary or a
      quantitative phenotype, but none has yet discussed the application of haplotype
      based association analysis to a survival outcome. We describe how the recently
      proposed Stochastic-EM (SEM) algorithm can be applied to estimate haplotype
      effects in censored data analysis using a standard Cox proportional hazards
      formulation. This model has been implemented in the THESIAS software freely
      available at http://www.genecanvas.org.

PMID- 15241486
TI  - Familial correlations and inter-relationships of four asthma-associated
      quantitative phenotypes in 320 French EGEA families ascertained through asthmatic
      probands.
AB  - Asthma is a complex disease, associated with biological and physiological
      phenotypes including immunoglobulin E (IgE) levels, sum of positive skin prick
      tests to allergens (SPTQ), eosinophil counts (EOS) and percent predicted forced
      expiratory volume in 1 s (%FEV1). We investigated the patterns of familial
      correlations and the inter-relationships of these four quantitative phenotypes,
      using the general class D regressive model, in 320 French EGEA nuclear families
      ascertained through 204 offspring (set A) and 116 parents (set B). Familial
      correlations of IgE and SPTQ were consistent with a model including no spouse
      correlation and equal parent-offspring and sib-sib correlations (rhoPO = rhoSS =
      0.25 for IgE and 0.15 for SPTQ), this model being compatible with an additive
      polygenic model in the whole sample and the two family subsets A and B. Different
      patterns of familial correlations of EOS and %FEV1 were observed in these two
      sets. In set A, the best fitting model included no spouse correlation and
      equality of parent-offspring and sib-sib correlations (rhoPO = rhoSS = 0.14 for
      EOS and 0.23 for %FEV1). In set B, EOS had only a significant rhoSS of 0.28,
      while %FEV1 had significant rhoMO of 0.28 and rhoSS of 0.16. Analysis of shared
      familial determinants between these phenotypes indicated an overlap of at most
      30% in rhoFO for IgE and SPTQ and in both rhoFO and rhoMO for IgE and EOS, while
      determinants of %FEV1 and atopy-related phenotypes appear distinct. These results
      may have implications for further linkage and association studies with genetic
      markers.

PMID- 15241487
TI  - MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in
      viable cells, and at additional sites with cytotoxic okadaic acid or taxol.
AB  - BCL2 family members are subject to regulation at multiple levels, providing
      checks on their ability to contribute to tumorigenesis. However, findings on post
      translational BCL2 phosphorylation in different systems have been difficult to
      integrate. Another antiapoptotic family member, MCL1, exhibits a difference in
      electrophoretic mobility upon phosphorylation induced by an activator of PKC (12
      O-tetradecanoylphorbol 13-acetate; TPA) versus agents that act on microtubules or
      protein phosphatases 1/2A. A multiple pathway model is now presented, which
      demonstrates that MCL1 can undergo distinct phosphorylation events - mediated
      through separate signaling processes and involving different target sites - in
      cells that remain viable in the presence of TPA versus cells destined to die upon
      exposure to taxol or okadaic acid. Specifically, TPA induces phosphorylation at a
      conserved extracellular signal-regulated kinase (ERK) site in the PEST region
      (Thr 163) and slows turnover of the normally rapidly degraded MCL1 protein;
      however, okadaic acid and taxol induce ERK-independent MCL1 phosphorylation at
      additional discrete sites. These findings add a new dimension to our
      understanding of the complex regulation of antiapoptotic BCL2 family members by
      demonstrating that, in addition to transcriptional and post-transcriptional
      regulation, MCL1 is subject to multiple, separate, post-translational
      phosphorylation events, produced in living versus dying cells at ERK-inducible
      versus ERK-independent sites.

PMID- 15241489
TI  - [Histological changes of the distal ileum in chronic diarrhea associated with
      megaloblastic anaemia].
AB  - Histological changes of the distal ileum were evaluated in thirteen (13) patients
      suffering from chronic diarrhea associated with Megaloblastic Anaemia (MA). The
      patients were seven (7) men and six (6) women with an average age of 55.6 (34
      74). They were all diagnosed with MA and treated with cianocobalamin and folic
      acid, which resulted in fast recovery. Follow up on the patients did not show any
      other cause related to chronic diarrhea. Biopsies from the distal ileum were
      taken by colonoscopy. Endoscopy findings were not relevant except for a light
      paleness or slightly-rough mucose. The following changes were found by examining
      the histological radiographies: chronic inflammatory infiltration 92% (12),
      intestinal villous atrophy 62% (8), erosions at villous surface 46% (6), slight
      ectasia of the lymphatics 46% (6), flattening of the epithelium cells of the
      villous 38% (5), and focal fibrosis 38% (5). The patients suffering chronic
      diarrhea associated with MA showed significant changes of the distal intestinal
      mucose (ileum). Those changes are probably also in the surrounding area and could
      explain not only the chronic diarrhea, but the poor absorption observed on some
      of the patients. The quick response to cobalamins and folates treatment showed
      the important role of these elements in intestinal restoration.

PMID- 15241490
TI  - [Basal fecal fermentation and with lactulose in patients with flatulence].
AB  - Determinations of the fecal fermentation in subjects may be very useful to know
      the fermentative capacity of his colonic bacteria. Determinations of basal fecal
      fermentation (FFB) and fecal fermentation with lactulose (FFL) were done in 30
      normal subjects and 126 patients with flatulence, especially meteorism. The media
      +/- s.d. of FFB was significantly higher in the normal subjects than in the
      patients with flatulence (1.82 +/- 1.55 vs. 1.24 +/- 1.40 ml of gas/24 h; P:
      0.015). On the contrary, in patients with flatulence the obtained media +/- s.d.
      of FFL and of the differences between FFL and FFB (FFL-FFB) were significantly
      and markedly higher than in the normal subjects (respectively: 8.84 +/- 5.55 vs.
      5.72 +/- 3.72 ml of gas/24 h, P: 0.004; and 7.60 +/- 5.05 vs. 3.91 +/- 3.22 ml of
      gas/24 h, P<0.00001). The obtained results seem to indicate that patients with
      flatulence tend to have a colonic flora with high fermentative capacity.

PMID- 15241491
TI  - [Diagnosis effectiveness of albumin in ascitic fluid].
AB  - Albumin in ascitic fluid has been evaluated as a discriminative diagnosis test,
      based on an observation and retrospective study, comparing it to that of total
      ascitis protein and albumin gradient, which are the most clinically used tests
      nowadays. The study involved a total of 45 patients, predominantly women,
      averaging 54 years of age, who were diagnosed through laparoscopy in a public
      hospital. The evaluation included: 19 patients suffering transudate type ascitis
      (chronic liver disease, n = 18), 23 patients with exudates type ascitis
      (peritoneal carcinomatosis, n = 12, tuberculous peritonitis, n = 11), and
      patients with mixedascitis. Sensibility, specificity and predictive values were
      obtained from the analysis of the tests, and they were represented through the
      distribution of averages and ROC curves, showing every time that these tests can
      be used in clinical practice because they have comparable sensibility and
      specificity values. As a new discriminative test of transudates and exudates the
      albumin test in ascitis proved to have a sensibility comparable to that of the
      protein in ascitic fluid but discreetly lower to that of albumin gradient.
      However, the ascitis albumin showed a better relation between the sensibility and
      specificity in the area under the ROC curves. Based on this study, the usefulness
      of the concentration of albumin in ascitic fluid is highlighted as a new test to
      discriminate exudates from transudates, which has been reported by very few
      authors in writing. In addition, this study shows that the albumin gradient can
      also be applied in the discrimination of exudates and transudates with efficacy
      comparable to its use in the discrimination of ascitis with or without portal
      hypertension.

PMID- 15241492
TI  - [Clinical and epidemiological profile of ulcerative colitis in a hospital in
      Lima].
AB  - The Non-specific Ulcerative Colitis (NUC) is an inflammatory disease of the
      rectum and the colon that can extend from the distal part of the rectum to the
      colon. Only in rare occasions is the terminal ileum compromised. OBJECTIVE: To
      know the clinic and epidemiological profile of the NUC, in the Edgardo Rebagliati
      Martins Hospital-EsSALUD (Lima-Peru). METHOD: Prospective and descriptive study
      of 43 patients diagnosed with NUC, from June, 2001 to May, 2003. RESULTS: The
      patients were 27 women (62.8%) and 16 men (37.2%); 31 from previous analysis
      (72.1%) and 12 new patients (27.9%); the largest compromised age group was
      between 30 to 39 years old (23.3%). The main symptoms were diarrhea (86%), rectal
      bleeding (58.1%), and abdominal pain (37.2%). Follow-up showed: remission
      (65.1%), recurrence (28%), persistency (2.3%) and fulminant course (2.3%). One
      patient died (2.3%). The colon compromise was: rectosigmoid (32.6%), left
      (30.3%), pancolitis (20.9%), to transverse (9.3%) and distal (6.9%). CONCLUSIONS:
      The incidence was of 2.1 cases per year, the average age was 45 years old (at the
      time of diagnosis), with a prevalence of women (62.8%). The main symptoms were
      diarrhea, rectal bleeding and abdominal pain. The main factor of recurrence was
      the interruption of the medication and anaemia was a frequent problem observed in
      the follow-up.

PMID- 15241493
TI  - [Human fasciolasis and gastrointestinal compromise: study of 277 patients in the
      Cayetano Heredia National Hospital (1970-2002)].
AB  - This is a retrospective and descriptive review of 277 patients suffering
      fasciolasis. These patients were seen in Hospital Nacional Cayetano Heredia
      between 1970-2002; 240 (86.6%) developed the chronic phase and 37 (13.3%) the
      acute form. Group aged 20-29 years were the most affected (24%). The main places
      infected were the interandean valleys of Lima, Ancash and Junin. The 277 patients
      the main symptoms were: abdominal pain in 236, nausea/vomiting in 106 and
      diarrhea in 100. Hepatomegaly in 56, pallor in 44 and fever in 23 were the main
      physical findings. 47% (80/169) suffered eosinophilia, 46% (38/82) had an
      increase of alkaline phosphatase and 31% (52/169) anemia.

PMID- 15241495
TI  - Update on the pathogenesis and immunotherapy of esophageal squamous cell
      carcinoma.
AB  - The esophageal squamous cell carcinoma (ESCC) is the prevailing histology subtype
      of esophageal cancer and is distinguished by its high mortality and its
      geographic differences in regards to its incidence. The exact cause of this
      neoplasia is still unknown in spite of all the research made in this area. Our
      understanding about pathogenesis, epidemiology and behaviour of the ESCC is still
      in progress thanks to the advances on the field of molecular biology. Some of
      these advances include the research of etiopathogenesis (virus, as the human
      papillomavirus, and the genes susceptible to cancer), genes associated with
      tumors (oncogenes, tumor suppressor genes), as well as new forms of neoadjuvant
      immunotherapy for the treatment of this neoplasia.

PMID- 15241494
TI  - [Hyperendemicity of human fasciolosis in the Mantaro Valley, Peru: factors for
      infection with Fasciole hepatica].
AB  - A sample of 206 children (between 1 and 16 years-old) in Huertas (n = 110) and
      Julcan (n = 96) districts of the Mantaro Valley, Peru, were studied with a
      clinico-epidemiological interview, serology and fecal parasitologic tests to
      describe the prevalence and analyze risk factors of infection by Fasciola
      hepatica (Fh). Fh prevalence by fecal examinations in Huertas (H) was 28.3% and
      Julcan (J), 12.6%. Using serological tests, the prevalences were: for H, 36.3%
      and for J, 22.7%. Univariate analysis showed a significant association between Fh
      infection and 3 variables in H: living near small streams (OR= 4.8; P < 0.05) or
      farms (OR= 2.88; P < 0.05) and the habit of drinking hot herbal drinks
      "emolientes" (OR= 2.92; P < 0.05); and in other 3 variables in J: having a single
      room per house (OR= 21.0; P < 0.05), defecating in the fields (OR= 4.77; P <
      0.05), history of taking antiparasitic medication in the last six months (OR=
      4.61; P < 0.05). Multivariate analysis, applied to the whole set of data revealed
      as possible risk factors for infection with Fh: the habit of drinking
      "emolientes" (OR= 5.16; P < 0.05) and living near small streams (OR= 17.22; P <
      0.05) or in farms (OR= 8.13; P < 0.05). According to these results one of the
      most important and less recognized risk factors is the habit of drinking
      "emolientes". Due to the clinical importance of human fascioliasis, we conclude
      that its presence in the Mantaro Valley is an important public health problem,
      effective early diagnosis would allow rapid treatment and avoidance of the
      serious impairment brought by chronic infection.

PMID- 15241496
TI  - [Are granulomas necessary for the final diagnosis of Crohn disease?].
AB  - A case of a 38 year-old male patient, from Lima, with a three-year period
      illness, characterized by abdominal pain, diarrhea, ponderal weight loss and
      fever is showed. He is examined by colonoscopy, with endoscopic diagnosis of
      colon cancer and undergoes surgery. The histopathological diagnosis was severe
      acute and chronic ulcerative ileocolitis, suggesting Crohn disease. A month later
      he again showed abdominal pain, diarrhea and fever, so a new colonoscopy is
      performed revealing multiple ileum ulcers and in the anastomotic area. The biopsy
      revealed an acute and chronic inflammatory process. The colon radiography showed
      a filling defect and irregularity in the cecum, and the upper endoscopy revealed
      esophageal ulcers. In addition, a number of analyses were carried out, such as:
      coproculture, HIV, and VK on sputum and feces, as well as CEA dosage, resulting
      all of them negative. The thorax radiography was also normal.He was diagnosed
      with Crohn's disease and was treated with mesalacin. Evolution was fast, showing
      weight gain, which allowed the discharge of the patient from the hospital seven
      (7) days later. The anatomical pathology never did confirm the final diagnosis,
      which brings us to the question:Are the granulomas always necessary for the final
      diagnosis of Crohn's disease?

PMID- 15241497
TI  - Quality of life related to visual function in three young adults with
      mucopolysaccharidoses.
AB  - The systemic mucopolysaccharidoses are complex syndromes, which may include
      corneal clouding as a mechanism leading to decreased vision and hence decreased
      quality of life. This study presents three young adult patients with
      mucopolysaccharidoses in order to compare their visual status through
      retrospective chart review, including patient and guardian interview, history,
      and examination, including a modified form of the VF-14 questionnaire (visual
      function with 14 questions). When the visual acuity and VF-14 results of the
      three patients were compared, the results of the VF-14 correlated with the
      patients" visual acuity status. The two patients who retained clear corneas or
      underwent penetrating keratoplasty had a wider range of social and physical
      activities, and an overall better quality of life than did the patient with
      decreased vision due to opacified corneas. We conclude that close monitoring of
      the ocular health of patients with storage syndromes that may compromise visual
      acuity must be stressed, and intervention to insure good vision is of the utmost
      importance to maintaining a good quality of life for these patients, especially
      as new therapies assist these patients to achieve increased longevity with better
      health.

PMID- 15241498
TI  - Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose,
      insulin, true triglyceride, and total cholesterol levels in Wistar rats.
AB  - In animals deprived of food for a long period, a drop in the fat mass below 5% of
      the total body mass results in an increase in blood glucocorticoids and uric acid
      levels, followed by foraging activity. Since the glucocorticoids increase the
      uric acid excretion, an increase in the level of uric acid in the bladder urine
      could be the signal for this feeding behaviour and subsequent fat storage.
      Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia,
      hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or
      hibernation. It is hypothesized that uric acid or its structurally related
      compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines
      namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and
      some drugs), can act on the urinary bladder mucosa and increases the blood
      glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the
      urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric
      acid results in a significant increase in the serum levels of glucose, insulin,
      true triglyceride, and total cholesterol in comparison with perfusion of the
      bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl
      uric acid acts on the urinary bladder mucosa and increases the serum glucose,
      insulin, true triglyceride, and total cholesterol levels.

PMID- 15241499
TI  - Health needs of adults with intellectual disability relevant for the family
      physician.
AB  - People with developmental disability, mental retardation, or intellectual
      disability are living longer and becoming prone to age-related health problems
      and diseases of old age much like the general population. This worldwide trend is
      also seen in Israel, where today 39.8% of persons with intellectual disability in
      residential care are 40 years old and above. There is a need for service and
      staff providers to receive training; a need for more research and better service
      for this aging population. This review presents health concerns for older persons
      with different levels of intellectual disability, health concerns in persons with
      Down syndrome, and persons with epileptic seizures and cerebral palsy in relation
      to general practice and family medicine. The review is concluded with
      recommendations on health and aging in adults with intellectual disabilities and
      the call for formalized training in the topic for specialists in family medicine.

PMID- 15241500
TI  - Introduction of an N-terminal peptide of S100C/A11 into human cells induces
      apoptotic cell death.
AB  - S100 proteins belong to the EF-hand Ca2+-binding protein family and are involved
      in the regulation of a variety of cellular processes. Individual S100 proteins
      are expressed in cell- and tissue-specific manners, and functional deterioration
      of S100 proteins leads to a number of human diseases, including cancer. We
      previously demonstrated that S100C/A11 was translocated to nuclei and inhibited
      DNA synthesis in human keratinocytes when exposed to high Ca2+. In the present
      study we examined the effects of synthetic partial peptides of S100C/A11 on human
      carcinoma cell lines. Only an N-terminal peptide with 19 amino acid residues
      (MAK19) showed cytotoxicity to the cell lines in dose- and time-dependent manners
      when introduced into cells by flanking the HIV-TAT protein transduction domain
      (TAT-MAK19). Pulse field electrophoresis revealed that DNA of the treated cells
      was partially degradated. Annexin V, a marker of cellular apoptosis, was detected
      in the cells treated with TAT-MAK19 by immunostaining and flow cytometry. The
      induction of apoptotic cell death was apparently independent of p53,
      p21WAF1/CIP1, and caspase activity, but treatment with TAT-MAK19 resulted in
      partial translocation of apoptosis-inducing factor (AIF) from the cytoplasm to
      nuclei. These results indicate that MAK19 induces apoptosis in human cell lines
      and may therefore lead to the establishment of a new molecular target for the
      treatment of human cancer.

PMID- 15241501
TI  - Antibodies from a DNA peptide vaccination decrease the brain amyloid burden in a
      mouse model of Alzheimer's disease.
AB  - The neuropathology of Alzheimer's disease(AD) is characterized by the
      accumulation of amyloid peptide Abeta in the brain derived from proteolytic
      cleavage of the amyloid precursor protein (APP). Vaccination of mice with plasmid
      DNA coding for the human Abeta42 peptide together with low doses of preaggregated
      peptide induced antibodies with detectable titers after only 2 weeks. One serum
      was directed against the four aminoterminal amino acids DAEF and differs from
      previously described ones. Both immune sera and monoclonal antibodies solubilized
      preformed aggregates of Abeta42 in vitro and recognized amyloid plaques in brain
      sections of mice transgenic for human APP. Passive immunization of transgenic AD
      mice caused a significant and rapid reduction in brain amyloid plaques within 24
      h. The combined DNA peptide vaccine may prove useful for active immunization with
      few inoculations and low peptide dose which may prevent the recently described
      inflammatory reactions inpatients. The monoclonal antibodies are applicable for
      passive immunization studies and may lead to a therapy of AD.

PMID- 15241502
TI  - [Adult-onset primary immunodeficiencies].
AB  - Different individuals with the same kind of primary immunodeficiency may start
      having symptoms from early childhood on, or alternatively much later in adult
      life, or never. The differences in phenotype can only partly be deduced from
      genotype-analysis or--in case of female patients with X-linked diseases--from age
      related skewing of lyonisation. The role of compensatory immune mechanisms is
      less clear. The microbial spectrum of infections is usually the same for both
      adult and infantile forms of a special primary immunodeficiency syndrome. Yet,
      many of the adult forms are associated with non-infectious complications, such as
      granuloma formation, autoimmunity or tumors. Besides standard antibiotic
      treatment and IgG replacement therapy, there are now different cytokine- or
      enzyme-replacement regimens available for some of the primary immunodeficiencies.
      However, exact diagnostic classification of the immunodeficiency should be
      obtained before such treatment modalities are used. Adult primary
      immunodeficiency syndromes therefore represent a challenge to both clinicians and
      molecular biologists.

PMID- 15241503
TI  - [The genetic revolution-impact on therapy and prevention].
AB  - After the successful sequencing of the human genome the genetic variation between
      individuals will be worked out in the near future. The genetic differences are
      the basis for different predispositions to diseases. The next goal is to
      correlate the host of genetic variants with phenotypes. This endeavor has already
      been successful for monogenic diseases; however, it will also be possible in
      genetically complex diseases. If a trait follows a monogenic mode of inheritance,
      a phenotype results nearly completely from a single mutation; in genetically
      complex diseases there exists only a statistical relationship. Predictive genetic
      diagnostics should only be considered after genetic counseling; it makes sense,
      if there exists efficient prevention or therapy, respectively. This applies e. g.
      to various familial cancer predispositions. In the future, medical doctors should
      be able to apply genetic risk figures and to convey them to their patients.

PMID- 15241504
TI  - [Primary prevention of diabetes mellitus type 2].
AB  - The increasing incidence of type 2 diabetes constitutes a considerable individual
      and socio-economic risk, therefore preventive concepts are urgently needed. Three
      prospective studies show that a "life-style-intervention" as well as drugs can
      prevent the development of diabetes as well as cardiovascular complications: The
      Diabetes Prevention Study (DPS) evaluated the influence of a "life-style
      intervention". The Diabetes Prevention Program (DPP) additionally examined the
      effect of metformin. In the STOP-NIDDM-Study acarbose was used for diabetes
      prevention and cardiovascular endpoints were also evaluated. The incidence of
      type 2 diabetes can be significantly reduced by a "life-style-intervention" and
      also by the administration of metformin or acarbose. With acarbose cardiovascular
      events are reduced significantly and comparably to a therapy with statins in
      primary prevention.

PMID- 15241505
TI  - [Palliative treatment options for esophageal and gastric cancer].
AB  - There are several different approaches available for the palliation of esophago
      gastric cancer. The decision on which type of therapy is used should be made
      individually based on an interdisciplinary consensus.In case of inoperable
      esophageal carcinoma, it becomes the primary objective of the therapy to maintain
      oral nutrition. This can be achieved through the insertion of self expanding
      metal stents as a minimally invasive procedure which results in an immediate
      elimination of dysphagia. As alternative and/or complementary therapy,
      radiological techniques (external beam radiation, brachytherapy) can be applied.
      Other locally endoscopic techniques (laser, APC-beamer) are often used for
      treating local complications of esophageal and inoperable stomach carcinomas. For
      these carcinomas palliative chemotherapy with cisplatin has been established as a
      standard regimen.

PMID- 15241506
TI  - [Hypopituitarism].
AB  - Hypopituitarism is usually caused by tumours of the hypothalamus-pituitary
      region, but may also arise as the consequence of pituitary inflammation,
      infiltration or hypoperfusion. Tumour mass reduction by surgical intervention or
      following drug treatment may improve pituitary function. However, neurosurgical
      tumour resection and radiation therapy may lead to a permanent manifestation of
      hypopituitarism. Diagnosis is established by endocrine testing, revealing the
      characteristic low serum concentrations of both peripheral hormone and associated
      regulatory hormone of pituitary origin. Hypopituitarism may involve from one to
      all endocrine axes regulated by the pituitary (in order of frequency: growth
      hormone deficiency>secondary hypogonadism>secondary hypothyroidism>secondary
      adrenal failure). The treatment of permanent hypopituitarism consists of
      replacement of the peripheral hormones (hydrocortisone, DHEA, thyroxine,
      testosterone or oestradiol, growth hormone). Quality of life is impaired in a
      considerable number of patients with hypopituitarism and mortality is increased,
      mostly due to cardiovascular and cerebrovascular causes, but also as a
      consequence of recurrent respiratory infections. Long-term care and monitoring of
      patients with hypopituitarism requires the experienced endocrinologist.

PMID- 15241509
TI  - [Acute aspiration and trismus due to tetanus].
AB  - Tetanus is a worldwide health problem, causing the deaths of approximately
      1,000,000 people every year. In Germany, about 15 infections are reported
      annually. The initial symptoms often develop in the head and neck region. As a
      result, some patients are referred to the otorhinolaryngologist. We report on a
      83 year old female who suffered from recurrent aspiration and trismus. She had
      acquired a small injury on her lower leg 2 weeks earlier; protective antibody
      levels did not exist. The neurophysiological examination showed a result typical
      of tetanus. The patient received tetanus immunoglobulin, metronidazole and
      benzodiazepines. Due to respiratory problems, tracheotomy and ventilation became
      necessary. Elderly people often lack protective antibody levels against tetanus.
      If typical symptoms are manifest, tetanus has to be considered as a possibility.
      A complete history, including recent injuries and past vaccinations, should be
      compiled.

PMID- 15241510
TI  - [Aquaporine. Discovery, function, and significance for otorhinolaryngology].

PMID- 15241511
TI  - [Relapsing facial erysipelas caused by nickel allergy. Significance of allergy
      diagnostics in ENT practice].
AB  - This case report shows a typical complication of allergic contact dermatitis as
      it is often seen in hand and foot eczema: relapsing erysipelas. To our knowledge
      the occurrence of such a complication in the face has never been reported. In the
      case presented, relapsing facial erysipelas were treated four times in a period
      of 2 years symptomatically without having identified or eliminated the causing
      allergen. This clearly indicates how important it is to have a sound knowledge of
      allergology and its diagnostic procedures, especially in ENT-practice.

PMID- 15241512
TI  - [Mitochondrial hearing impairment. Background, genetic predisposition and
      possibilities for diagnosis].
AB  - Hearing impairment (HI) is one of the most common neurosensory disorders, with
      sensorineural hereditary HI being the most common form. Mitochondrial maternally
      inherited HI appears to be increasing in frequency. The incidence of
      mitochondrial defects causing HI is estimated to be between 6 and 33% of all
      hearing deficiencies, with an even higher percentage for some syndromic cases.
      This review summarises the syndromic and non-syndromic characteristics of
      sensorineural HI based on mutations in mitochondrially encoded genes, the
      relationship to aminoglycoside-induced HI and related diagnostic tools.

PMID- 15241513
TI  - [Speech impaired children. Anxiety, depression and quality of life of the
      mothers].
AB  - BACKGROUND: It is widely held that the well being of a mother significantly
      influences the way she brings up her child: Mothers with depression speak less to
      their child than healthy mothers do and so their emotional disorder has to be
      regarded an important cofactor for their child's speech development. On the other
      hand it is suspected that a mother's well being and quality of life may be
      influenced by her child especially in cases when the child suffers from
      impairment or developmental disturbance. As literature provides only little
      information on this topic the purpose of this study was to estimate both health
      related quality of life HRQOL and distinctive emotional reactions i.e. depression
      and anxiety in mothers of children with a speech developmental disorder.
      MATERIALS AND METHODS: 100 mothers (age 33.4+/-5.3 years, range: 22 to 47 years)
      of 100 preschool children (32 girls, 68 boys; age 4.2+/-1.5 years, range 1;3 to
      7;7 years) with a speech impairment were investigated. Mothers of children with
      cochlear hearing loss, syndromes or other developmental disorders were excluded
      from the study. To estimate the prevalence of anxiety disorders and depression in
      the mothers the German version of the Hospital Anxiety and Depression Scale
      (HADS) was used. Data from 157 healthy women from the German test manual served
      as controls. HRQOL was assessed by the SF-36 questionnaire with age matched
      normal controls taken from the German test manual. Microsoft((R)) Excel and
      Matlab((R)) software packages were used for description, analysis, and
      evaluation. The differences in prevalence rates were tested by chi(2)-test and
      Wilcoxon's rank sum test. RESULTS: Assessed by the HADS-depression subscale 11%
      of the mothers of speech impaired children met criteria for depression compared
      to 2.5% in the control group. The prevalence in the study group was significantly
      higher ( p<0.01). The prevalence of anxiety disorders did not differ from
      normative data on a significant level ( p>5%). The SF-36 questionnaire revealed
      lower scores of most SF-36 subscales on different significance levels. The
      results of both tests correlated on a statistically significant level.
      CONCLUSIONS: Screening mothers of speech impaired children for a "soft" parameter
      like HRQOL and for epidemiologically relevant emotional disorders like depression
      and anxiety is of significant clinical interest. The SF-36 and the HADS are
      suitable tests. As the results of both tests are highly correlated for clinical
      purposes it seems reasonable to focus on depression and anxiety only. Up to now
      no data exist about how fathers of speech impaired children react emotionally, so
      this question has to be focused on in future. Although data allow no conclusion
      on whether the speech impairment is the reason or the consequence of a reduced
      HRQOL or an emotional disorder the results clearly indicate the necessity to take
      into account the mothers' well being when dealing with speech impaired children.

PMID- 15241514
TI  - [Paragangliomas in the head-/neck region. I: Classification and diagnosis].
AB  - Paragangliomas of the head and neck occur sporadically or are hereditary. The
      hereditary phenotype characteristically occurs between the 2nd and 3rd decade of
      life; the sporadic phenotype beyond the 4th decade. The hereditary phenotype
      "paraganglioma syndrome type 1" frequently shows multilocular tumor
      manifestations and rarely cases of maltransformation. Therefore, paragangliomas
      should be considered a systemic disease. For diagnosis, an interdisciplinary,
      step by step procedure is mandatory comprising genetic screening, whole body
      medical check-up including catecholamine metabolism, and optionally an 18F-Dopa
      PET and localised imaging procedures.

PMID- 15241515
TI  - [Off-label use in dermatological practice. The conflict between professional duty
      and legal requirements].
AB  - When making therapeutic decisions, doctors often find themselves faced with a
      dilemma regarding ethical, professional, legal liability, social and service
      aspects of their duties. These conflicts may be enhanced when medications have to
      be prescribed for non-approved usages, known as off-label prescribing, because
      existing therapy options have been exhausted. This option become considerably
      more difficult since the German Federal Social Court decision of March 2002 which
      limited off-label use to a number of very strictly defined circumstances. In
      order to clarify the basis for taking decisions in a given situation, an oncology
      expert commission has been formed under the coordination of the Department of
      Health and Social Security. However, this is no solution for the great variety of
      uncommon dermatological diseases which often require off-label medication usage.

PMID- 15241516
TI  - [Medical advance directives as instruments of patient self-determination].
AB  - Medical advance directives and durable powers of attorney for health care
      increasingly gain importance and recognition as instruments of patient self
      determination. This article explores the various possibilities for advance
      directives as well as their ethical legal background. Furthermore, results of a
      current patient and population survey are presented, showing how (potential)
      patients think about the possibilities of advance directives. Finally, practical
      recommendations on how to deal with medical advance directives are given.

PMID- 15241517
TI  - [Taking responsibility for one's own health. Possibilities and limits using the
      example of malignant melanoma].
AB  - Because of the persistent shortage of health care resources, scientists and
      politicians are discussing ways to increase the patients' personal responsibility
      for their own health. Based on a philosophical analysis of the concept of
      responsibility, this article tries to assess strengths and limits of a personal
      responsibility for health, illustrated by the prevention of cutaneous melanoma.
      On the one hand, individuals bear prospective responsibility for their health
      status by adopting a healthy lifestyle and participating in prevention programs.
      On the other hand, individuals can--retrospectively--be held responsible for
      those conditions that result from the voluntary choice of health risks.
      Considering the tremendous practical and ethical problems associated with
      retrospective responsibility, prevention and public health policies should
      emphasize prospective personal responsibility for health.

PMID- 15241518
TI  - [Communication in oncology].
AB  - Patient-doctor communication is an essential aspect of coping with cancer. In our
      "age of communication", information and data transfer often is mistaken for
      communication. Contrary to analogous or digital information transmission, a
      message received by the patient may widely differ from the message intended by
      the doctor. For in human communication, nonverbal and emotional contexts may
      extensively modify the perception, interpretation and processing of information.
      Moreover, in modern oncology patient-doctor communication is complicated by a
      growing incongruence between a patient's disease and his illness experience. To
      achieve satisfying doctor-patient communication, the setting, content and
      structure have to be directed towards a specific goal. Empirical data show that
      key elements and skills of efficient patient-doctor communication can be taught
      and learned.

PMID- 15241519
TI  - [Psychosocial counseling of skin cancer patients in these times of diagnosis
      related groups (DRG)].
AB  - Patients with skin cancer suffer from very specific distress. Highly distressed
      patients need an unburdening support, enabling them to develop an active-
      cognitive coping style. In the past, an approach to psycho-oncological
      intervention which proved beneficial offered basic support to all patients and
      additional help to overburdened patients and their relatives. The introduction of
      the diagnosis related groups (DRG)-a system of all inclusive compensation-has
      endangered this approach because psychosocial care is not sufficient recognized
      and reimbursed for by DRG. Within the framework of already implemented structural
      alterations and focal shifts of content, different approaches to future psycho
      oncological care for patients with skin cancer will be presented.

PMID- 15241520
TI  - ["Smoldering systemic mastocytosis. "Successful therapy with cladribine].
AB  - Mastocytoses are a heterogenous group of diseases characterized by proliferation
      and accumulation of mast cells in the skin and other organs. They are subdivided
      into cutaneous mastocytoses; systemic forms, which may appear with or without
      skin lesions; mast cell sarcomas and extracutaneous, localized, benign
      mastocytomas. Systemic mastocytoses apart from the skin mainly involve bone
      marrow, gastrointestinal tract, bones, lymph nodes, spleen and liver. Whereas
      indolent forms of systemic mastocytosis are mainly treated with antihistamines,
      glucocorticosteroids and PUVA therapy, the more aggressive forms, including mast
      cell leukemia, often require cytostatic chemotherapy. A 53-year old patient with
      beginning "smoldering systemic mastocytosis" failed to respond to high-dose
      systemic glucocorticosteroids and interferon-alpha. Treatment with cladribine led
      to an impressive improvement of skin lesions, a significant decrease in tryptase
      serum levels and stabilization of bone marrow infiltrates.

PMID- 15241521
TI  - [Pruritic nodules in an 81-year-old patient].

PMID- 15241522
TI  - [Methods of sentinel lymph node mapping].
AB  - Sentinel lymph node mapping is used as a diagnostic method in order to increase
      staging accuracy without the well-known morbidities of radical lymphadenectomy.
      The sentinel node is defined as the first node to receive lymphatic drainage from
      a primary tumor. The sentinel node concept postulates that if the first draining
      node is negative for metastasis, the remaining lymph nodes in the nodal basin can
      be spared. Thus one can predict the status of the nodal basin with high accuracy.
      It also shows that lymphatic spread seems to follow certain rules that do not
      concern the whole lymphatic basin. Skip metastases were proven to be rare in
      breast and gastric cancer. The main issue in sentinel lymph node mapping remains
      the improvement of staging accuracy for detection of lymph nodes most likely to
      develop metastasis as well as reducing morbidity by planning lymphadenectomies
      individually for each tumor and each patient.

PMID- 15241523
TI  - [IKOP-Infection control in the operating theatreConsensus on the theme "Barrier
      measures during operations and invasive procedures"].
AB  - Postoperative surgical site infections remain frequent despite intensive control
      programs. With rising numbers of operations and invasive procedures in the
      outpatient setting and in immunocompromised patients, the prevention of wound
      infections presents a rapidly growing challenge to the medical community. Barrier
      measures including drapes and surgical gowns to prevent wound contamination, have
      clearly reduced the rate of wound infections. The optimal material
      characteristics for operating gowns and drapes are well defined, but there is
      still a long running controversy on the use of single-use versus reusable
      materials. We review the efficacy and ecological impacts of these different
      approaches. Currently no superiority of any of these approaches with regard to
      either efficacy or ecological impact can be found. The European Union has
      recently published a series of mandatory standards to specify material
      characteristics of barrier materials used in operating theatres (EN 13795). Their
      scope include production standards of these materials as well as specific
      processes in auditing their characteristics. The implementation of these norms
      will clearly present a challenge to European hospitals but will lead to better
      material characteristics in the end.

PMID- 15241524
TI  - [Iloprost. Pharmacology and clinical application during surgery].
AB  - Iloprost is a long-acting prostacyclin analogue with potent vasodilating
      properties. When applied per inhalation, iloprost rapidly and remarkably reduces
      pulmonary vascular resistance and thereby pulmonary artery pressure for
      approximately 60-120 min. In addition, if iloprost is inhaled and not infused,
      major systemic side-effects such as a significant reduction of the systemic
      arterial pressure can mostly be circumvented. Inhaled iloprost can be applied by
      means of ultrasound or by oxygen flow with both techniques being available for
      intensive care ventilators. For use in the anaesthesia circuit a special
      construction was built.

PMID- 15241525
TI  - ["Meet the AIX-PERTs." Emergency medical care at the beginning of the medical
      reform curriculum in Aachen].
AB  - BACKGROUND: Extensive knowledge and skills in the basics of emergency medical
      care are of paramount importance for every physician and should therefore be an
      integral part of medical education. METHODS: Regulations for medical licensure in
      Germany were revised by the administrative authorities in 2002 and as a
      consequence the Medical Faculty of the University of Aachen (Germany) decided to
      start the Medical Reform Curriculum Aachen. A multidisciplinary, problem-oriented
      and organ-related approach to medical education replaces the classical
      discrimination between basic and clinical sciences. RESULTS: With AIX-PERT (AIX
      la-Chapelle Program for Emergency medical care and Resuscitation Training), a
      program consisting of problem-based learning sessions was developed for
      introduction to the first year students. Defined teaching objectives in emergency
      medicine are now incorporated in undergraduate medical education. CONCLUSION: The
      extremely positive evaluation of the new approach encouraged us to promote AIX
      PERT further. In the future the effects of success of this approach will be
      assessed by longitudinal studies of skills and knowledge during the continuing
      curriculum.

PMID- 15241526
TI  - [Unwanted wakefulness during general anesthesia].
AB  - Intraoperative wakefulness ("awareness") is still a relevant problem. Different
      stages of wakefulness exist: conscious awareness with explicit recall of pain in
      0.03% and with nonpainful explicit recall in 0.1-0.2% of all anesthesias; amnesic
      awareness or implicit recall may occur with unknown, even higher incidences.
      Sufficient analgesia minimizes possible painful perceptions. Opioids,
      benzodiazepines, and N(2)O alone or combined lead to the highest incidences of
      nonpainful intraoperative wakefulness. Volatile anesthetics, etomidate,
      barbiturates, and propofol in sufficient doses effectively block any sensory
      processing and therefore abolish intraoperative wakefulness. Intraoperative
      awareness with recall may lead to sustained impairment of the patients, in severe
      cases even to a post-traumatic stress disorder (PTSD). The observation of
      clinical signs does not reliably detect intraoperative wakefulness in all cases;
      monitoring of end-tidal gas concentrations, EEG, or evoked potentials may help in
      prevention. Active information is recommended only for patients at higher risk.
      Complaints about recall of intraoperative events should be taken seriously; in
      cases of sustained symptoms psychological help may be necessary.

PMID- 15241527
TI  - Radiotherapy for high-grade gliomas. Does altered fractionation improve the
      outcome?
AB  - BACKGROUND AND PURPOSE: The publication of Radiation Therapy Oncology Group
      (RTOG) Study 83-02 in 1996 stimulated further investigations of altered
      fractionation, i. e., application of more than one fraction per day, in high
      grade gliomas. This review summarizes the results of trials published between
      January 1997 and June 2002. MATERIAL AND METHODS: To identify suitable trials, a
      Medline search was performed by use of the following key words: brain
      tumors/astrocytoma/glioma/high-grade glioma/malignant glioma/glioblastoma
      multiforme and accelerated radiotherapy/hyperfractionated radiotherapy/altered
      fractionation. In addition, the search was extended to reference lists of
      articles and textbooks. Whenever possible, data were extracted from the original
      papers on an intention-to-treat basis, i. e., patients with protocol violations
      were not excluded for the purpose of this analysis. Studies in brain stem
      gliomas, pediatric patients and studies which achieved acceleration by
      radiosurgery, stereotactic radiotherapy, or brachytherapy rather than
      conventional external-beam treatment were not included. An exploratory analysis
      of 2-year survival was also performed. For this purpose, the 2-year survival rate
      was extracted from each individual study. The total number of 2-year survivors
      was then calculated for each treatment strategy and compared by use of the chi(2)
      test. RESULTS: The authors identified 1,414 patients from 21 studies; two of
      these were randomized phase III studies. In seven studies (658 patients),
      chemotherapy or radiosensitizers were not administered in addition to
      radiotherapy. The others provide a very heterogeneous set of data, because a
      large variety of drugs and administration schedules was used. Seven studies
      included patients with glioblastoma multiforme only, two were limited to patients
      with anaplastic gliomas. Dose per fraction was 1.2-1.8 Gy in 17 studies and 1.9
      2.65 Gy in four. Overall treatment time was 12-31 days, except for one study.
      Three out of five studies where three fractions per day were administered,
      included a 2-week break (split-course studies). None of the studies reported a
      significant improvement in survival by altered fractionation in comparison to
      either institutional historical controls or their respective randomized control
      arm. Doses of 60-70 Gy do not appear to improve survival compared to 50-60 Gy.
      The current data provide no arguments for use of three instead of two fractions
      per day. Median survival was 10 months after radiotherapy alone (658 patients)
      and 11 months after combined treatment (756 patients). Regarding 2-year survival
      rates, radiotherapy alone resulted in 13%, combined chemoradiation or use of
      sensitizers in 23% (p < 0.0001). However, prognostic factors such as tumor
      histology were not equally distributed and favor the combined-treatment group.
      Evaluation of six studies of conventional radiotherapy alone resulted in data
      from 571 patients. Their median survival was 10.8 months. Cumulative 2-year
      survival amounted to 15%. The studies of conventional radiotherapy plus
      chemotherapy or sensitizers included 1,115 patients with a median survival of 11
      months (2-year survival rate 18.5%). CONCLUSION: Altered fractionation shortens
      the overall treatment time for adult patients with supratentorial high-grade
      gliomas. However, there is no significant survival improvement.

PMID- 15241528
TI  - Immediate postoperative radiotherapy or "watch and wait" in the management of
      adult low-grade glioma?
AB  - BACKGROUND: The EORTC Trial 22845 on the role of immediate postoperative
      radiotherapy in patients with supratentorial lowgrade glioma revealed an
      advantage of immediate postoperative radiotherapy for progression-free survival,
      but not for overall survival. It is still an open question in which clinical
      setting immediate radiotherapy should be considered and whether chemotherapy may
      become a useful alternative. MATERIAL AND METHODS: Reports in the literature
      spanning 60 years of radiation therapy were reviewed with respect to timing of
      radiotherapy, prognostic factors, dose prescriptions, modern treatment
      techniques, and late effects. Data on chemotherapy were also reviewed. Based on
      these data, the role of immediate postoperative radiotherapy or chemotherapy in
      adult low-grade glioma is presented. RESULTS: Radiotherapy is able to control
      symptoms in up to 80% of cases. Malignant transformation occurs in 36-86% of
      cases upon progressive disease. Long-term median survival crucially depends on
      prognostic factors and ranges between 12 months and 10 years. Radiotherapy does
      not cause neurocognitive deficits, provided that modern treatment techniques and
      moderate dose prescriptions are used. Recent series with small patient numbers
      indicate that chemotherapy using PCV or temozolomide may prolong median survival
      and induces response rates of 50% in oligodendroglial tumors. CONCLUSION: The
      arguments for immediate postoperative irradiation include: low-grade gliomas
      respond to radiotherapy; the tumors often display an aggressive pathobiological
      behavior; patients with high risk profile may benefit from immediate radiotherapy
      in terms of progression-free and overall survival; modern focal radiotherapy is
      far less toxic than feared; radiotherapy might be more effective at diagnosis
      than at progression. Chemotherapy might be an alternative in immediate
      postoperative treatment. Its role, however, is unclear. The forthcoming
      prospective trial of the EORTC will address this issue in a randomized setting.

PMID- 15241529
TI  - Proton therapy of uveal melanomas in Berlin. 5 years of experience at the Hahn
      Meitner Institute.
AB  - BACKGROUND AND PURPOSE: In June 1998, proton-beam therapy of ocular tumors
      started at the Hahn-Meitner Institute Berlin, Germany. The purpose of the present
      study is to evaluate treatment outcome for uveal melanomas. PATIENTS AND METHODS:
      245 consecutive patients with primary melanoma of the uvea were treated from June
      1998 to April 2003 with a 68-MeV proton beam. In 96.2% of all patients, a uniform
      fractionation scheme was applied: single dose 15 CGE (cobalt gray equivalent),
      total dose 60 CGE on 4 consecutive days. Follow-up is available in 229 patients.
      RESULTS: At the time of median follow-up (18.4 months), local control is 96.4%
      and 95.5% at 3 years. Eye retention rate is 92.6% at 20 months (median follow-up)
      and 87.5% at 3 years. CONCLUSION: Proton-beam irradiation of uveal melanomas at
      the Hahn-Meitner Institute after the first 5 years of its initiation reveals
      local tumor control and eye retention rates in the range of other centers with
      larger experience. Delivering high treatment quality in hadron therapy from the
      beginning has been achieved.

PMID- 15241530
TI  - Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An
      analysis of 43 consecutive patients.
AB  - BACKGROUND: Despite numerous randomized trials suggesting a benefit of
      unconventional fractionation in locally advanced head and neck cancer, the role
      of this approach in nasopharyngeal carcinoma is debatable. Based on the current
      clinical experience, the authors introduced hyperfractionated irradiation in the
      treatment of locally advanced head and neck cancer, including nasopharyngeal
      tumors. The preliminary results of this treatment approach in nasopharyngeal
      cancer patients are presented, with special focus on the pattern of failure and
      toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II
      IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy
      was preceded by a median of three cycles of cisplatin-based induction
      chemotherapy. Irradiation was delivered using a shrinking-field technique up to a
      total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h
      interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy
      was significant but tolerable. Mucositis proved the most common side effect
      (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not
      observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks
      after completion of radiotherapy, complete response was seen in 35 patients
      (81%), partial response in five (12%), stable disease in one, and progressive
      disease in two. After a median follow-up of 32 months, 18 patients (41%)
      developed progressive disease. Primary tumor progression was observed in three
      patients, and seven patients each showed regional lymph node progression and
      distant metastases. In one case both regional lymph node progression and distant
      metastases were diagnosed. The 2-year progression-free survival and overall
      survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated
      radiotherapy seems a feasible and active regimen in locally advanced
      nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and
      does not compromise delivery of the planned irradiation dose. This regimen is
      associated with a high local control rate; relatively high nodal and distant
      failure, however, call for further treatment modifications, e. g., optimization
      of irradiation technique and/or dose escalation as well as improved systemic
      therapies.

PMID- 15241531
TI  - Early effects of irradiation on [(123)I]-IMT and [(18)F]-FDG uptake in rat C6
      glioma cells.
AB  - BACKGROUND: Single-photon emission computed tomography (SPECT) using 3-[(123)I]
      iodo-L-alpha-methyltyrosine ([(123)I]-IMT) and positron emission tomography (PET)
      using 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) are valuable tools for the
      distinction between viable tumor and radionecrosis in patients receiving
      radiotherapy for high-grade gliomas. However, to date, little is known about the
      early effects of radiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas.
      MATERIAL AND METHODS: To determine the early effects of irradiation on [(123)I]
      IMT and [(18)F]-FDG uptake in gliomas, in vitro studies were performed using rat
      C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common
      dose applied to patients receiving intraoperative radiotherapy. Subsequently, the
      early kinetics of [(123)I]-IMT and [(18)F]-FDG uptake in glioma cells were
      monitored for 3 days. RESULTS: Micromorphometric examinations of the irradiated
      glioma cells revealed that about 25% of the viable cells transformed into giant
      cells. [(123)I]-IMT uptake per 10(5) viable glioma cells was unchanged on the 1st
      day post irradiation, but showed a significant increase on the 2nd and 3rd day
      following radiotherapy (p < 0.01). In addition, there was a moderate increase in
      [(18)F]- FDG accumulation per 10(5) viable glioma cells during the first 3 days
      after irradiation (p < 0.05). The maximum increase in early [(123)I]-IMT uptake 1
      h after application surpassed that of [(18)F]-FDG (p < 0.01). CONCLUSION: Rat C6
      glioma cells show an early increase in [(123)I]-IMT and [(18)F]-FDG uptake
      following irradiation which may be partly due to giant cell formation. These data
      suggest that [(123)I]-IMT SPECT and [(18)F]-FDG PET may be promising procedures
      for the early prediction of the therapeutic response of gliomas to radiotherapy.

PMID- 15241532
TI  - Irradiation induces a biphasic expression of pro-inflammatory cytokines in the
      lung.
AB  - BACKGROUND AND PURPOSE: The precise pathophysiological mechanisms of radiation
      induced lung injury are poorly understood, but have been shown to correlate with
      dysregulation of different cytokines. The purpose of this study was to evaluate
      the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF
      )alpha, interleukin-(IL-)1alpha and IL-6 after whole-lung irradiation. MATERIAL
      AND METHODS: The thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated
      and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8,
      16, and 24 weeks post irradiation (p. i.). Real-time multiplex RT-PCR (reverse
      transcriptase polmyerase chain reaction) was established to evaluate the
      expression of TNF-alpha, IL-1alpha and IL-6 in the lung tissue of the mice. For
      histological analysis, lung tissue sections were stained by hematoxylin and
      eosin. RESULTS: Multiplex RT-PCR analysis revealed a biphasic expression of these
      pro-inflammatory cytokines in the lung tissue after irradiation. After an initial
      increase at 1 h p. i. for TNF-alpha and at 6 h p. i. for IL-1alpha and IL-6, the
      mRNA expression of these pro-inflammatory cytokines returned to basal levels (48
      h, 72 h, 1 week, 2 weeks p. i.). During the pneumonic phase, TNF-alpha, IL-1alpha
      and IL-6 were significantly elevated and revealed their maximum at 8 weeks p. i.
      Histopathologic evaluation of the lung sections obtained within 4 weeks p. i.
      revealed only minor lung damage in 5-30% of the lung tissue. By contrast, at 8,
      16, and 24 weeks p. i., 70-90% of the lung tissue revealed histopathologically
      detectable organizing alveolitis. CONCLUSION: Irradiation induces a biphasic
      expression of pro-inflammatory cytokines in the lung. The initial transitory
      cytokine response occurred within the first hours after lung irradiation with no
      detectable histopathologic alterations. The second, more persistent cytokine
      elevation coincided with the onset of histologically discernible organizing acute
      pneumonitis.

PMID- 15241533
TI  - Iodine-125 brachytherapy of brain stem tumors.
AB  - PURPOSE: To report on iodine-125 ((125)I) interstitial irradiation in the
      treatment of brain stem tumors. PATIENTS AND METHODS: Two patients with brain
      stem tumors were treated with CT- and image fusion-guided (125)I stereotactic
      brachytherapy. RESULTS: By March 2003, the patients had been followed up for 47
      and 13 months, respectively. In case 1, the tumor volume was 1.98 cm(3) on the
      control CT, indicating a 65.5% shrinkage as compared to a target volume of 5.73
      cm3 at the time of brachytherapy. In case 2, shrinkage was more distinct. After
      irradiation, the cyst volume was 0.16 cm(3) on the control MRI, indicating a
      97.4% shrinkage as compared to a target volume of 6.05 cm(3) at the time of
      brachytherapy, i. e., the metastasis had virtually disappeared. CONCLUSION: CT-
      and image fusion-guided (125)I stereotactic brachytherapy can be performed during
      the biopsy session. The procedure can be well planned dosimetrically and is
      surgically precise.

PMID- 15241534
TI  - Glioblastoma with spinal seeding.
AB  - BACKGROUND: Extracranial seeding of glioblastoma multiforme (GBM) is very rare
      and its development depends on several factors. This case report describes two
      patients suffering from GBM with spinal seeding. In both cases, the anatomic
      localization of the primary tumor close to the cerebrospinal fluid (CSF) was the
      main factor for spinal seeding. CASE REPORTS: Two patients with GBM and spinal
      seeding are presented. After diagnosis of spinal seeding, both patients were
      highly symptomatic from their spinal lesions. Case 1 experienced severe pain
      requiring opiates, and case 2 had paresis of lower limbs as well as urinary
      retention/incontinence. Both patients were treated with spinal radiation therapy.
      Nevertheless, they died 3 months after diagnosis of spinal seeding. RESULTS: In
      both patients the diagnosis of spinal seeding was made at the time of cranial
      recurrence. Both tumors showed close contact to the CSF initially. Even though
      the patients underwent intensive treatment, it was not possible to keep them in a
      symptom-free state. CONCLUSION: Because of short survival periods, patients
      deserve optimal pain management and dedicated palliative care.

PMID- 15241535
TI  - [Cardiorespiratory fitness. Importance of sports for health].
AB  - Epidemiologic studies have established that physical activity is associated with
      substantial improvements in cardiovascular prognosis. The effect of physical
      activity appears to be in the order of traditional risk factors such as smoking
      or hypercholesterolemia. The strength of evidence is best for intensive activity,
      corresponding to an energy expenditure > 6 METs (metabolic equivalent).
      Cardiorespiratory fitness can be determined directly by using treadmill- or
      bicycle-based exercise stress testing. Exercise stress testing in healthy
      subjects shows that in the lowest quintile of fitness distribution,
      cardiovascular morbidity and mortality are greatly increased. Prognosis improves
      significantly when reaching a higher level of fitness (better than the worst
      20%). Physical activity exerts beneficial effects on cardiovascular risk factors
      and on subclinical atherosclerosis (e. g., endothelial function, progression of
      atherosclerotic plaques), and it reduces cardiovascular endpoints. An increase in
      cardiorespiratory fitness by 1 MET brings along a risk reduction of approximately
      20%. Physical exertion itself is associated with an increased risk of sudden
      cardiac death, which is alleviated, however, by regular training. All in all, the
      risk-benefit relation is very favorable and better than for most other
      interventions.

PMID- 15241536
TI  - [Endurance training and cardial adaptation (athlete's heart)].
AB  - One essential function of the cardiovascular system is to provide an adequate
      blood supply to all organs, including the skeletal muscles at rest and during
      exercise. Adaptation to chronic exercise proceeds mainly via the autonomic
      nervous system. On the one hand, peripheral muscles influence the autonomic
      reactions through "feedback" control via ergoreceptors, in particular, mechano-
      and chemoreceptors. On the other hand, there is central control in the sense of a
      "feed forward" regulation, e. g., the reaction of an athlete before competition.
      Along with other influential factors, such as circulatory presso-, chemo-, and
      volume receptors, the incoming impulses are processed in vegetative centers.A
      cardiovascular reaction, then, is the result of nerval and humoral sympathetic
      and parasympathetic activity. At rest, the parasympathetic tone dominates. It
      reduces heart frequency and conduction velocity. The high vagal tone is initially
      reduced with increasing physical exertion and switches at higher intensity to
      increasingly sympathetic activation. This mechanism of reaction to exercise is
      supported by inverse central and peripheral transmissions.Chronic endurance
      training leads to an improved local aerobic capacity of the exercised
      musculature. At rest, it augments parasympathetic activity when the muscle mass
      is sufficiently large, i. e., 20-30% of the skeletal musculature. The extent of
      the adaptation depends on individual factors, such as scope, intensity of
      training, and type of muscle fiber. A higher vagal tone delays the increase in
      the sympathetic tone during physical exertion. The regulatory range of heart
      rate, contractility, diastolic function, and blood pressure is increased. In
      addition, adaptation results in functional and structural changes in the vascular
      system. Cardiocirculatory work is economized, and maximum performance and oxygen
      uptake are improved. Endurance training exceeding an individual limit causes
      harmonic enlargement and hypertrophy of the heart. The thickness of both, the
      septum and posterior wall increases to the same extent as the interior volume.
      The mass/volume ratio, and therefore the maximum systolic wall stress, remains
      constant in contrast to pathologic forms of hypertrophy. Adaptations, including
      function and size of the heart, show a regression in healthy inactive persons
      without any structural heart disease.

PMID- 15241537
TI  - [Sports as therapy].
AB  - Over the last 2 decades the clinical application of physical exercise as a
      therapeutic strategy has developed from rehabilitation to prevention and
      treatment of cardiovascular diseases. This shift in clinical application was
      accompanied by a more systematic research approach of the involved mechanisms and
      the objective clinical assessment of sport interventions using prospective
      randomized clinical trials. This ongoing process established physical exercise as
      an evidence-based and guideline-oriented treatment option. In stable coronary
      artery disease (CAD), exercise therapy has long been used for rehabilitation
      purposes following an acute myocardial infarction. A recent meta-analysis
      revealed a significant 27% reduction of total mortality among training patients.
      Four mechanisms are considered important mediators of the reduced cardiac event
      rate: improvement of endothelial function, reduced progression of coronary
      lesions, reduced thrombogenic risk, and improved collateralization. The
      therapeutic benefit of regular physical exercise has also been confirmed in
      direct comparison with an interventional strategy: a 12-month exercise therapy in
      stable CAD patients was associated with a higher event-free survival as compared
      to conventional percutaneous coronary intervention. In stable chronic heart
      failure (CHF), physical activity was traditionally discouraged-with negative
      consequences for the patients: exercise intolerance worsened, the progression of
      disease-related muscular atrophy accelerated. A carefully designed exercise
      program at 50-70% of the maximal oxygen uptake was effective in improving
      exercise capacity by 12-32%. In a recent meta-analysis, exercise therapy reduced
      the relative risk of CHF mortality by 35% and CHF-related hospitalizations by
      28%. Considering the growing body of evidence in favor of sport as a therapy,
      training interventions should be considered additional/alternative therapeutic
      strategies as compared with established pharmacological/interventional options.

PMID- 15241538
TI  - [Physical activity and sports in heart failure due to myocarditis and dilated
      cardiomyopathy].
AB  - BACKGROUND: Sudden cardiac death of suspected healthy young athletes is a rare,
      but deeply moving event. Usually, the affected person has been completely free of
      symptoms. Commonly, unrecognized inflammatory, hypertrophic or dilated
      cardiomyopathies are the most frequent causes. All therapeutic principles of
      angiotensin-converting-enzyme (ACE) inhibition, beta-blockade, and diuretics in
      heart failure aim to unload the heart. During physical activity increased
      sympathetic tonus and loading conditions for the heart point into the opposite
      direction. This raises the question to what extent physical activity in patients
      with myocarditis, dilated cardiomyopathy or heart failure in general is
      tolerable. SYNOPSIS: Several experimental studies revealed disadvantages of
      physical exercise during acute myocarditis leading to an increase in mortality.
      On the other hand, several small trials in men demonstrate an improvement of
      physical fitness and quality of life attributed to controlled supervised exercise
      training in patients with heart failure without assessment of mortality. Dilated
      cardiomyopathy was diagnosed in one third of these patients. There was no biopsy
      confirmation of these conditions. The other two thirds of patients suffered from
      ischemic heart diseases. CONCLUSION: Since the borderline between inflammatory
      heart disease and noninflammatory or postinflammatory dilated cardiomyopathy is
      difficult to determine, abstention from physical training during and shortly
      after inflammatory heart disease is recommended, because it is known that viral
      persistence or autoimmune processes could last for several months.

PMID- 15241539
TI  - [Hypertension and exercise. Sports methods for the hypertensive patient].
AB  - Physical exercise is of paramount therapeutic importance in nonpharmacological
      interventions of arterial hypertension. The extent and the effects of exercise on
      blood pressure lowering are analyzed according to the actual literature. Suitable
      and nonsuitable activities are considered. Dynamic isotonic endurance training is
      more effective than static isometric exercise. A rather low or moderate extent of
      endurance training lowers the systolic and diastolic blood pressure by
      approximately 5-11 mmHg and 3-8 mmHg, respectively. This effect of exercise can
      be achieved besides the favorable effects on other cardiovascular risk factors.
      Intensity of exercise should be monitored by the heart rate. The mean intensity
      should not exceed 70% of the maximal heart rate. An initial ergometry might be
      suitable for the planning of training recommendations.

PMID- 15241540
TI  - [Scuba diving and the heart. Cardiac aspects of sport scuba diving].
AB  - Diving with self-contained underwater breathing apparatus (scuba) has become a
      popular recreational sports activity throughout the world. A high prevalence of
      cardiovascular disorders among the population makes it therefore likely that
      subjects suffering from cardiovascular problems may want to start scuba diving.
      Although scuba diving is not a competitive sport requiring athletic health
      conditions, a certain medical fitness is recommended because of the physical
      peculiarities of the underwater environment. Immersion alone will increase
      cardiac preload by central blood pooling with a rise in both cardiac output and
      blood pressure, counteracted by increased diuresis. Exposure to cold and
      increased oxygen partial pressure during scuba diving will additionally increase
      afterload by vasoconstrictive effects and may exert bradyarryhthmias in
      combination with breath-holds. Volumes of gas-filled body cavities will be
      affected by changing pressure (Figure 1), and inert gas components of the
      breathing gas mixture such as nitrogen in case of air breathing will dissolve in
      body tissues and venous blood with increasing alveolar inert gas pressure. During
      decompression a free gas phase may form in supersaturated tissues, resulting in
      the generation of inert gas microbubbles that are eliminated by the venous return
      to the lungs under normal circumstances. Certain cardiovascular conditions may
      have an impact on these physiological changes and pose the subject at risk of
      suffering adverse events from scuba diving. Arterial hypertension may be
      aggravated by underwater exercise and immersion. Symptomatic coronary artery
      disease and symptomatic heart rhythm disorders preclude diving. The occurrence of
      ventricular extrasystoles according to Lown classes I and II, and the presence of
      atrial fibrillation are considered relative contraindications in the absence of
      an aggravation following exercise. Asymptomatic subjects with Wolff-Parkinson
      White syndrome may be allowed to dive, but in case of paroxysmal supraventricular
      tachycardia they must refrain from diving. Pacemakers will fail with increasing
      pressure, but some manufacturers have proven their products safe for pressure
      equivalents of up to 30 m of seawater, so that patients may dive uneventfully
      when staying within the 0-20 m depth range. Significant aortic or mitral valve
      stenosis will preclude diving, whereas regurgitation only will not be a problem.
      Right-to-left shunts have increasingly gained attention in diving medicine, since
      they may allow venous gas microbubbles to spill over to the arterial side of the
      circulation enabling the possibility of arterial gas embolism. Significant shunts
      thus preclude diving. The highly prevalent patent foramen ovale is considered a
      relative contraindication only when following certain recommendations for safe
      diving (Table 2). Metabolic disorders are of concern, since adiposity is
      associated with both, higher bubble grades in Doppler ultrasound detection after
      scuba dives when compared to normal subjects, and an increased epidemiologic risk
      of suffering from decompression illness. In conclusion, cardiovascular aspects
      are important in the assessment of fitness to dive, and certain cardiovascular
      conditions preclude scuba diving. Any history of cardiac disease or abnormalities
      detected during the routine medical examination should prompt to further
      evaluation and specialist referral.

PMID- 15241541
TI  - [Sports death--an Internal Medicine problem?].
AB  - Sports means fitness and endurance, regeneration and balance, game and fun. Lack
      of physical exercise is one of the main risk factors for cardiovascular diseases.
      Terrifying and not conclusive in the public's mind are events of sudden death, in
      particular if those are of nontraumatic cause and thus of cardiovascular origin.
      Organic pathologic examination revealed that a higher proportion of males are
      affected by sports death. Only 7-9% of those events are related to women,
      although the percentage of active women among sports people accounts for nearly
      50%. The relative risk increases with age and intensity of endurance. For people
      who are untrained or not used to train, the risk of sudden death is potentially
      higher. In athletes > 35 years of age, coronary artery disease (CAD) is the most
      common cause (85%) of sudden death. In the group < 35 years, CAD and acute
      myocarditis are the predominant causes of sudden death, but also hypertrophic
      cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC),
      disorders of the conducting system, and Marfan's syndrome. Additional risk
      factors like acute infections and misuse of doping drugs require the care of a
      specialist in internal medicine and/or cardiology on top of the care by a
      specialist in orthopedics and accident/rehabilitation medicine. Physical
      examination as a precaution and prevention strategy should be available for
      leisure sports as well as for athlete sports.

PMID- 15241542
TI  - [Cardiac arrhythmia in sports].
AB  - Cardiac arrhythmias in athletes are frequent events in medical practice and
      require a profound diagnostic procedure. It is necessary to differentiate between
      harmless alterations of cardiac rhythm and potentially dangerous arrhythmias.
      While the former are mostly the result of an increased vagotone as a consequence
      of endurance training, the latter are raising the question whether intensive
      physical and mental strains in competitive exercise are compatible with the
      cardiac arrhythmias diagnosed. Vagotone-induced alterations of cardiac
      arrhythmias generally disappear under exercise conditions. It is essential to
      include the type, intensity and duration of the athletic activities into the
      differential-diagnostic evaluations. However, those medical considerations
      frequently collide with economic interests. Sinus bradycardia is a typical
      example of vagotone-induced arrhythmias, which may be observed especially in
      highly endurance-trained athletes. Sinus bradycardias are mostly asymptomatic and
      rarely the cause of grave complications; therapeutic interventions are only
      required if clinical symptoms such as orthostatic disturbances are present. The
      different variants of cardiac conduction defects are-within certain limits-also
      frequently induced by an increased vagotone; generally, they require an intensive
      cardiologic diagnosis. Another frequent form of arrhythmias are ventricular
      extrasystoles. Their dignity may be assessed by exercise ECG. Disappearance under
      exercise conditions is, generally, a positive sign. Diagnosis and therapy of
      cardiac arrhythmias are based on the established guidelines. Additionally,
      regular cardiologic screenings are required in high-performance athletes of all
      age groups.

PMID- 15241543
TI  - [Sports and pregnancy].
AB  - MATERNAL ASPECTS: Cardiorespiratory responses to exercise in pregnant women
      generally don't differ from those in nonpregnant women. Impairment of the
      cabability of the uteroplacental unit to maintain a sufficient oxygen and
      substrate supply to the fetus should be avoided by performing exercise in a
      submaximal range. Increase in body weight, a shift of the center of gravidity,
      and the ligamentous laxity in pregnancy lead to a certain joint instability and
      consecutively to an increased risk of injury. Therefore contact sports and sports
      with a high potential of injury are not suitable in pregnancy. Furthermore the
      beneficial effects of exercise on glucose metabolism especially in pregnant women
      with an impaired glusose tolerance, psychological well-being, delivery, and
      lactation are discussed. FETAL ASPECTS: Exercise results in an elevation of the
      fetal heart rate. So far no pathological heart rate alterations could be
      observed. There are controversial findings concerning the influence of exercise
      on birth weight. Actually no retardation below the 10th percentile could be
      demonstrated. To prevent pregnancy complications like preterm labour or placental
      abruption exercises with a risk of blunt abdominal trauma are not recommended in
      the 2nd and 3rd trimester. Additionally the effects of exercise on embryogenesis
      and the possible implications of hyperthermia are presented. CONCLUSION: In
      general, pregnant women should practise exercise in a moderate, i. e. submaximal
      aerobic range. Preexisting cardiopulmonary diseases and pregnancy pathologies
      have to be considered as contraindications. Thus gestational age adapted exercise
      represents a safe and effective support for mother and fetus. Recommendations
      concerning exercise in pregnancy underwent significant changes during the past
      three decades. Today there is a lot of evidence for the beneficial effects of
      moderate exercise in pregnancy even in formerly inactive women. This review first
      presents aspects of maternal and fetal physiology with special respect to
      exercise in pregnancy. Subsequently, risks and contraindications as well as the
      suitability of different kinds of exercise for pregnant woman are discussed.

PMID- 15241544
TI  - [Sports after heart transplantation].
AB  - Heart transplantation has the potential to change a patient with a life
      threatening illness into an active healthy person with a potentially excellent
      quality of life. Survival with excellent allograft function for 10 years is now
      common for the majority of patients. However, exercise performance remains
      impaired when compared to healthy subjects. Reasons include a decrease of maximal
      heart rate, cardiac output and oxygen uptake, which are present after heart
      transplantation. The role of these abnormalities may differ as a function of time
      after surgery. Possible reasons like cardiac denervation, diastolic dysfunction,
      and endothelial dysfunction are discussed in this article. Furthermore, exercise
      capacity may be diminished because of peripheral limitations associated with
      physical deconditioning, abnormal muscle structure and function or
      pharmacological side effects. Endurance and strength training may greatly improve
      muscle function and maximal aerobic performance as well as reduce side effects of
      immunosuppressive therapy. Exercise should be considered a valuable tool in the
      long-term treatment after heart transplantation.

PMID- 15241545
TI  - An unusual reason for a diastolic murmur.

PMID- 15241546
TI  - [Aortic dissection and intramural hematoma: is the TEE the last word? Acute
      aortic syndrome].

PMID- 15241547
TI  - 50 years of passionate commitment.

PMID- 15241548
TI  - Lipopolysaccharide-binding molecules: transporters, blockers and sensors.
AB  - Lipopolysaccharide (LPS), a major component of the outer membrane of Gram
      negative bacteria, can be beneficial to the host by activating the innate immune
      system, or harmful, by inducing inflammation, disseminated intravascular
      coagulation, multiple organ failure, shock and often death. On the bacteria, and
      in host biological fluids and cells, LPS is never free but constantly attached to
      cognate-binding proteins. Understanding how LPS is transported and further
      recognized by sensors able to deliver a signal, or by inactivating molecules able
      to neutralize its biological effects, is an important goal. This review describes
      the large panel of peptides and proteins reported to associate with LPS, and
      provides information on their origin, their structure and the location of amino
      acid residues involved in their interaction with LPS. A better understanding of
      the mode of recognition of LPS by cognate proteins prompted many laboratories to
      design on a rational basis synthetic molecules which can be used to detect low
      amounts of endotoxin, or to act as efficient blockers of in vitro and in vivo
      responses to LPS.

PMID- 15241549
TI  - Regulating a translational regulator: mechanisms cells use to control the
      activity of the fragile X mental retardation protein.
AB  - Fragile X syndrome results from the loss of a normal cellular protein, FMRP. FMRP
      is an RNA binding protein, and it is likely that altering the way FMRP's
      messenger RNA (mRNA) targets are processed results in the clinical features
      associated with the disease. Using complementary DNA microarray screening, a
      number of brain-derived mRNAs that interact directly with FMRP in vitro and
      associate with FMRP-containing mRNPs in vivo have been identified. These target
      messages encode RNA-binding proteins, transcription factors, neuronal receptors,
      cytoskeletal proteins, a few enzymes as well as several unknown proteins. For a
      subset of these mRNAs it has been shown that modulating FMRP levels in cultured
      cells correspondingly affects their expression. In addition, several modes by
      which cells modulate FMRP activity have been described; these include
      posttranscriptional processing and posttranslational modification. Here, the most
      recent results concerning the biochemical activities of FMRP and how they are
      affected by various modifications are reviewed. The data lead to a model
      signaling mechanism by which FMRP normally regulates the expression of its target
      mRNAs.

PMID- 15241550
TI  - Unraveling the pathogenesis of Parkinson's disease--the contribution of monogenic
      forms.
AB  - The field of Parkinson's disease pathogenesis is rapidly evolving from the one of
      a monolithic and obscure entity into the one of a complex scenario with several
      known molecular players. The ongoing systematic exploration of the genome holds
      great promise for the identification of the genetic factors conferring
      susceptibility to the common non-Mendelian forms of this disease. However, most
      of the progress of the last 5 years has come from the successful mapping and
      cloning of genes responsible for rare Mendelian variants of Parkinson's disease.
      These discoveries are providing tremendous help in understanding the molecular
      mechanisms of this devastating disease. Here we review the genetics of the
      monogenic forms of Parkinson's disease. Moreover, we focus on the mechanisms of
      disease caused by alpha-synuclein and parkin mutations, and the implications of
      this growing body of knowledge for understanding the pathogenesis of the common
      forms of the disease.

PMID- 15241551
TI  - The scorpine family of defensins: gene structure, alternative polyadenylation and
      fold recognition.
AB  - Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate
      immunity provide the first defense against infectious pathogens. This class of
      molecules exists widely in invertebrate hemolymph and vertebrate skin secretion,
      but animal venoms are emerging as a new rich resource. Scorpine is a unique
      scorpion venom defensin peptide that has an extended amino-terminal sequence
      similar to cecropins. From the African scorpion Opistophthalmus carinatus venom
      gland, we isolated and identified several cDNAs encoding four new homologs of
      scorpine (named opiscorpines 1-4). Importantly, we show for the first time the
      existence of multiple opiscorpine mRNAs with variable 3' untranslated regions
      (UTRs) in the venom gland, which may be generated by alternative usage of
      polyadenylation signals. The complete opiscorpine gene structure including its
      promoter region is determined by genomic DNA amplification. Two large introns
      were found to be located within the 5' UTR and at the boundary of the mature
      peptide-coding region. Such a gene structure is distinct, when compared with
      other scorpion venom peptide genes. However, a comparative promoter analysis
      revealed that both opiscorpine and scorpion venom neurotoxins share a similar
      promoter organization. Sequence analysis and structural modeling allow us to
      group the scorpines and scorpion long-chain K-channel toxins together into one
      family that shares a similar fold with two distinct domains. The N-terminal
      cecropin-like domain displaying a clear antimicrobial activity implies that the
      scorpine family represents a group of real naturally occurring hybrids. Based on
      the phylogenetic analysis, a possible cooperative interaction between the N and C
      domains is elucidated, which provides an evolutionary basis for the design of a
      new class of anti-infectious drugs.

PMID- 15241553
TI  - Acylphosphatase overexpression triggers SH-SY5Y differentiation towards neuronal
      phenotype.
AB  - An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y
      neuroblastoma cells, using a green fluorescent fusion protein (AcP-GFP), with GFP
      acting as a reporter protein. The cellular proliferation rate was significantly
      reduced by overexpression of AcPase by a factor of ten. In contrast, clones
      transfected with two inactive AcPase mutants showed a growth rate comparable to
      control cells. This suggests that AcPase catalyzes the proliferative down
      regulation. AcPase-overexpressing clones showed a physiological mortality rate as
      assessed by an MTT reduction test and by evaluation of necrotic markers. DNA
      fragmentation analysis and assays of caspase-3 and poly (ADP-ribose) polymerase
      (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase
      overexpression led to a marked increase in PARP activity as well as Bcl-2
      content; these are commonly up-regulated during differentiative processes in
      neuronal cells. In fact, the typical differentiation marker, growth-associated
      protein 43, was significantly up-regulated. Microscopic observations also showed
      a clear increase in the differentiative phenotype in AcPase-overexpressing cells.
      Our results clearly show that AcPase plays a primary causative role in neuronal
      differentiation.

PMID- 15241552
TI  - Oligomer-mediated modulation of hTERT alternative splicing induces telomerase
      inhibition and cell growth decline in human prostate cancer cells.
AB  - The expression of telomerase in human cells is strictly controlled by multiple
      mechanisms including transcription and alternative splicing of telomerase reverse
      transcriptase (hTERT). In this study, we demonstrated the possibility of
      modulating the hTERT splicing pattern in DU145 human prostate carcinoma cells
      through the use of 2'-O-methyl-RNA phosphorothioate oligonucleotides targeting
      the splicing site located between intron 5 and exon 6 in the hTERT pre-mRNA. An
      18-h oligonucleotide exposure induced a decrease in the full-length hTERT
      transcript and a concomitant increase in the alternatively spliced transcripts,
      which resulted in significant inhibition of telomerase catalytic activity.
      Moreover, exposure to the R7 oligomer (which induced the most pronounced
      modulation of the hTERT splicing pattern and the greatest telomerase inhibition)
      caused a marked reduction in DU145 cell growth and the induction of apoptosis
      starting 2 days after treatment. Such data support the concept that down
      regulation of hTERT expression can cause short-term effects on tumour cell
      growth, which are telomere-shortening independent.

PMID- 15241554
TI  - Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide
      modified liposomes.
AB  - Protein transduction domains (PTDs) are used to enhance cellular uptake of drugs,
      proteins, polynucleotides or liposomes. In this study, functionalized
      Antennapedia (Antp, aa 43-58) and HIV Tat (aa 47-57) peptides were coupled to
      small unilamellar liposomes via thiol-maleimide linkage. Modified liposomes
      showed higher uptake into a panel of cell lines including tumor and dendritic
      cells than unmodified control liposomes. Liposome uptake was time and
      concentration dependent as analyzed by flow cytometry and live-cell microscopy.
      At least 100 PTD molecules per small unilamellar liposome (100 +/- 30 nm) were
      necessary for efficient translocation into cells. Cellular uptake of PTD-modified
      liposomes was 15- to 25-fold increased compared to unmodified liposomes and was
      inhibited by preincubation of liposomes with heparin. Glycosaminoglycan-deficient
      CHO cells showed dramatically reduced cell association of PTD-modified liposomes,
      confirming the important role of heparan sulfate proteoglycans in PTD-mediated
      uptake. Antp-liposomes used as carriers of the cytotoxic drug N4-octadecyl-1-beta
      D-arabinofuranosylcytosine-(5'- 5')-3'-C-ethinylcytidine showed a reduction of
      the IC50 by 70% on B16F1 melanoma cells compared with unmodified liposomes. PTD
      functionalized liposomes, particularly Antp-liposomes, represent an interesting
      novel carrier system for enhanced cell-specific delivery of a large variety of
      liposome-entrapped molecules.

PMID- 15241555
TI  - N-acetylglucosaminyltransferase V modifies the signaling pathway of epidermal
      growth factor receptor.
AB  - Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human
      H7721 hepatocarcinoma cells resulted in an increase in the N
      acetylglucosaminebeta1,6mannosealpha1,3- branch (GnT-V product) on the N-glycans
      of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF
      binding and tyrosine autophosphorylation, but showed little effect on the
      expression of EGFR protein. The phosphorylation at T308, S473 and tyrosine
      residue(s) and the activity of protein kinase B (Akt/PKB) as well as the
      phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase
      (MEK) before and after EGF stimulation were concomitantly increased. Conversely,
      in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results were
      the reverse of those with GnTV-S-transfected cells. After the cells were treated
      with 1-deoxymannojirimycin, an inhibitor of N-glycan processing at high mannose,
      or antibody against the extracellular glycan domain of EGFR, the differences in
      PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and
      mock-transfected cells were significantly attenuated. These findings indicate
      that the altered expression of GnT-V will change the glycan structure and
      function of EGFR, which may modify downstream signal transduction.

PMID- 15241556
TI  - Aloe-emodin prevents cytokine-induced tumor cell death: the inhibition of auto
      toxic nitric oxide release as a potential mechanism.
AB  - Aloe-emodin (AE) is a plant-derived hydroxyanthraquinone with potential
      anticancer activity. We investigated the ability of AE to modulate survival of
      mouse L929 fibrosarcoma and rat C6 astrocytoma cells through interference with
      the activation of inducible nitric oxide (NO) synthase (NOS) and subsequent
      production of tumoricidal free radical NO. Somewhat surprisingly, AE in a dose
      dependent manner rescued interferon-gamma + interleukin-1-stimulated L929 cells
      from NO-dependent killing by reducing their autotoxic NO release. The observed
      protective effect was less pronounced in C6 cells, due to their higher
      sensitivity to a direct toxic action of the drug. AE-mediated inhibition of tumor
      cell NO release coincided with a reduction in cytokine-induced accumulation of
      transcription and translation products of genes encoding inducible NOS and its
      transcription factor IRF-1, while activation of NF-kappaB remained unaltered.
      These data indicate that the influence of AE on tumor growth might be more
      complex that previously recognized, the net effect being determined by the
      balance between the two opposing actions of the drug: its capacity to directly
      kill tumor cells, but also to protect them from NO-mediated toxicity.

PMID- 15241557
TI  - Cytochrome c release and endoplasmic reticulum stress are involved in caspase
      dependent apoptosis induced by G418.
AB  - G418 is used extensively in transfection experiments to select eukaryotic cells
      that have acquired neomycin resistance genes, but the mechanism is still elusive.
      To investigate this, we treated normal rat kidney cells with G418 for 3 days and
      found that the cells presented typical apoptotic features such as cell shrinkage,
      nuclear fragmentation, and caspase-3 activation. However, there was no low
      molecular DNA ladder. The pan caspase inhibitor z-VAD-fmk completely inhibited
      this type of apoptosis, suggesting a caspase-dependent mechanism. Caspase
      cascades in apoptosis induced by G418 were initiated by at least two pathways:
      the release of cytochrome c from mitochondria, which was observed under confocal
      microscopy, and endoplasmic reticulum stress, demonstrated by the increase in
      Ca2+ concentration and the cleavage of m-calpain and procaspase-12. Both pathways
      activated caspase-9. Inhibition of caspase-9 activity by z-LEHD-fmk prevented
      most of the cells from apoptosis, and E-64d, an inhibitor of calpain accentuated
      this block. The cleavage of caspase-9 and caspase-12 was blocked only by
      simultaneous application of z-VAD-fmk and E-64d, but not by either alone. E-64d
      did not prevent the release of cytochrome c. These results indicated that these
      two pathways were independent of each other.

PMID- 15241558
TI  - Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen
      1.
AB  - Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the
      basement membrane. To investigate the impact of MMP-19 activity on endothelial
      cells in the context of tumor extracellular matrix (ECM), we treated Matrigel
      matrix with an active recombinant MMP-19 and analyzed its effect on capillary
      like formation. Human microvascular endothelial cells (HMEC-1) could not form
      capillary-like formation on Matrigel treated with recombinant MMP-19. Analyzing
      the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The
      cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates
      the G3 globular domain containing the binding site for the gamma1 chain of
      laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1 to cross
      link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of
      nidogen-1 inhibited the capillary-like structure formation to a similar extent as
      MMP-19. Since nidogen-1 is thought to stabilize microvessels, MMP-19 might be one
      of the enzymes that interferes with stabilization or maturation of nascent
      vasculature.

PMID- 15241559
TI  - TSH receptor signaling via cyclic AMP inhibits cell surface degradation and
      internalization of E-cadherin in pig thyroid epithelium.
AB  - Incorporation of E-cadherin into the adherens junction is a highly regulated
      process required to establish firm cell-cell adhesion in most epithelia. Less is
      known about the mechanisms that govern the clearance of E-cadherin from the cell
      surface in both normal and pathological states. In this study, we found that the
      steady-state removal of E-cadherin in primary cultured pig thyroid cell
      monolayers is slow and involves intracellular degradation. Experimental
      abrogation of adhesion by a Ca2+ switch induces rapid cell surface proteolysis of
      E-cadherin. At the same time, endocytosed intact E-cadherin and newly synthesized
      E-cadherin accumulate in intracellular compartments that largely escape further
      degradation. Acute stimulation with thyroid-stimulating hormone (TSH) or
      forskolin prevents all signs of accelerated E-cadherin turnover. The findings
      indicate that TSH receptor signaling via cyclic AMP stabilizes the assembly and
      retention of E-cadherin at the cell surface. This suggests a new mechanism by
      which TSH supports maintenance of thyroid follicular integrity.

PMID- 15241560
TI  - Involvement of arginine vasopressin in endogenous central histamine-induced
      reversal of critical haemorrhagic hypotension in rats.
AB  - OBJECTIVE AND DESIGN: Histamine is a potent stimulator of arginine vasopressin
      (AVP) release and therefore, the role of AVP was studied in the reversal of
      critical haemorrhagic hypotension induced by endogenous central histamine after
      inhibition of histamine N-methyltransferase (HNMT) activity in rats. MATERIAL: In
      48 ethylurethane-anaesthetised male Wistar rats cardiovascular parameters and
      plasma hormone concentrations were measured. TREATMENT: Haemorrhage-shocked rats
      with mean arterial pressure (MAP) 20-25 mmHg were injected
      intracerebroventricularly (icv) with HNMT inhibitor metoprine (20 microg) after
      pre-treatment with V(1a), V(1b) and V(2) receptor antagonists - [beta-mercapto
      beta,betacyclopentamethylenepropionyl(1), O-me-Tyr(2),Arg(8)]AVP (10 microg/kg;
      iv), SSR149415 (10 mg/kg; ip) and [adamantaneacetyl(1),O-Et-D-Tyr(2),Val(4),
      aminobutyryl(6),Arg(8,9)]AVP (10 microg/kg; iv), respectively, or saline.
      METHODS: MAP, heart rate (HR) and regional haemodynamics were monitored within 2
      h after treatment or to death if it occurred earlier. Plasma hormone
      concentrations were measured using enzyme immunoassays. ANOVA followed by Neuman
      Keules test, and Fisher's exact test were used to compare the results. RESULTS:
      Metoprine produced a long-lasting increase in MAP, HR, renal, hindquarters and
      mesenteric blood flows, and a 100% survival at 2 h (P < 0.05 vs. the control
      group). The action was associated with increased plasma AVP concentration (587.5
      +/- 98.9 vs. 387.3 +/- 125.2 pg/ml; P < 0.05) in comparison to the control group
      as measured at 20 min after treatment. V(1a), but not V(1b) and V(2), receptor
      antagonist inhibited metoprine-induced haemodynamic effects, with no influence on
      survival at 2 h. SSR149415 did not influence ACTH and adrenaline plasma
      concentrations in the metoprine-treated group. CONCLUSION: AVP, acting via V(1a)
      receptors, is involved in endogenous central histamine-induced reversal of
      critical haemorrhagic hypotension in rats.

PMID- 15241561
TI  - Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor
      antagonist from human blood granulocytes and monocytes: evidence for the
      involvement of plasma IgG, complement C3 and beta2 integrin.
AB  - OBJECTIVE: Evolving evidence of anti-inflammatory effects is observed in patients
      with rheumatoid arthritis or ulcerative colitis following periodic adsorptive
      granulocyte and monocyte (GM) apheresis with a column containing cellulose
      acetate (CA) beads as apheresis carriers. This study was undertaken to obtain
      insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis
      with CA beads. METHODS: In a series of in-vitro experiments, we investigated the
      effects of plasma proteins and the leucocytes beta2 integrin (CD18) on
      granulocyte adsorption to CA beads. RESULTS: Granulocyte adsorption to CA beads
      required plasma IgG, the complement C3 and was inhibited by an antibody to
      leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1
      receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were
      released by granulocytes that adhered to CA beads. CONCLUSIONS: Plasma IgG, C3
      derived complement activation fragments and leucocytes CD18 are involved in
      granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.

PMID- 15241562
TI  - Pharmacological and histopathological characterization of Bothrops lanceolatus
      (Fer de lance) venom-induced edema.
AB  - OBJECTIVE: Bothrops venoms cause local edema, pain, hemorrhage and necrosis. In
      this study, we investigated the ability of Bothrops lanceolatus venom to cause
      edema in rat hind paws and examined the mediators involved. MATERIALS AND
      METHODS: Hind paw edema was induced in male Wister rats by the subplantar
      injection of venom (12.5-100 microg/paw) in the absence and presence of
      antagonists. Edema was quantified by hydroplethysmometry at 0.25, 0.5, 2, 4, 6
      and 24 h post-injection and was expressed as the percentage increase relative to
      the contralateral (control) paw. The ability of the venom to release histamine
      from rat peritoneal mast cells was also assessed. RESULTS: Venom caused dose- and
      time-dependent edema that was maximal within 15 min but disappeared after 24 h
      and was accompanied by hemorrhage. Dexamethasone (1 mg/kg, s.c.), methysergide (6
      mg/kg, i.p.), HOE 140 (0.6 mg/kg, i.v.) and mepyramine (6 mg/kg, i.p.)
      significantly ( p < 0.05) reduced edema formation, whereas indomethacin (10
      mg/kg, i.p.) was ineffective. Dialysis did not affect venom-induced edema. Venom
      (1, 10 and 30 microg/ml) caused a concentration-dependent release of histamine
      (13 +/- 1%, 61.9 +/- 4.6% and 73.6 +/- 2.4%, respectively; n = 5) from rat
      peritoneal mast cells in vitro. Histological analysis confirmed the presence of
      edema, hemorrhage and neutrophil infiltration. Pretreating the venom with EDTA
      partially inhibited the edema and hemorrhage, but did not affect the migration of
      neutrophils. CONCLUSIONS: B. lanceolatus venom produced dose- and time-dependent
      edema in rat paws. This edema was not dependent on low molecular weight
      substances in the venom, but was partially dependent on a hemorrhagin and also
      involved the release of arachidonic acid metabolites, bradykinin, histamine and
      serotonin.

PMID- 15241563
TI  - Protective effects of lactoferrin in Escherichia coli-induced bacteremia in mice:
      relationship to reduced serum TNF alpha level and increased turnover of
      neutrophils.
AB  - OBJECTIVE AND DESIGN: Previous studies demonstrated that lactoferrin (LF), given
      intravenously (i.v.), 24 h before lethal Escherichia coli ( E. coli) infection,
      protects mice against mortality. The aim of this investigation was to determine
      whether downregulation of serum TNF alpha activity and increase of neutrophil
      number in the circulation and bone marrow by LF could contribute to the
      protective action of LF against E. coli-induced sepsis. MATERIAL AND SUBJECTS:
      CBA female mice, 10-12 week old, weight 20-22 g, were used. TREATMENT: Mice were
      given 10 mg LF i.v. either 2 h or 24 h before i.v. administration of lethal dose
      of E. coli (5 x 10(8)). METHODS: Serum activities of TNF alpha and IL-1 were
      determined by bioassays 2 h following E. coli or LF injection. The blood and bone
      marrow smears were stained with Giemsa and May-Grunwald reagents and reviewed
      histologically. RESULTS: LF given 24 h before E. coli caused a 60% reduction of
      TNF alpha released into circulation. However, pretreatment of mice with LF 2 h
      before bacterial challenge resulted in strong (15 fold) increase of TNF alpha
      serum level. Analysis of bone marrow cell composition revealed a significant
      increase in neutrophil lineage cell content (myelocytes, bands and mature
      neutrophils) following 24 h pretreatment with LF (51.8% of the total cell count),
      versus PBS control (32.7%) and 2 h LF pretreatment (35.8%). The percentage of
      neutrophils (bands and mature forms) in the peripheral blood rose to 47.4% versus
      32% and 32%, respectively. Intravenous administration of LF increased also
      interleukin 1 (IL-1) concentration in the circulation of noninfected mice.
      CONCLUSIONS: This investigation has added more information regarding the
      mechanism of the protective action of LF in E. coli-induced bacteremia by
      revealing the phenomenon of accelerated neutrophil recruitment and down
      regulation of E. coli-induced TNF alpha serum level.

PMID- 15241564
TI  - The oral administration of retinoic acid enhances nociceptive withdrawal reflexes
      in rats with soft-tissue inflammation.
AB  - OBJECTIVE AND DESIGN: To study the involvement of all-trans retinoic acid (ATRA)
      in the development and maintenance of inflammatory pain. SUBJECTS: Adult male
      Wistar rats and murine neuro2a and human SH-SY5Y neuroblastoma cells. TREATMENT:
      Soft-tissue inflammation was induced by the intraplantar administration of 100
      microl of carrageenan lambda. The oral treatment with either ATRA or vehicle
      lasted for seven days and consisted in a dose of 15 mg/kg the first two days and
      a dose of 10 mg/kg the following five days. Neuroblastoma cells were incubated
      for 16 h with ATRA. METHODS: Rats were tested twice daily for intensity and
      evolution of withdrawal reflexes evoked by mechanical and thermal stimulation.
      The expression of COX enzymes was studied in spinal cords and neuroblastoma cells
      by western blot. RESULTS: The animals treated with ATRA showed a significantly
      more intense development of mechanical allodynia (p < 0.01), mechanical
      hyperalgesia (p < 0.01), thermal hyperalgesia (p < 0.001) and reduction of
      threshold for mechanical (29 +/- 4 vs. 60 +/- 6 mN, p < 0.001) and thermal
      stimulation (12 +/- 0.3 vs. 8.4 +/- 0.3 s, p < 0.001) than control animals.
      Recovery to mechanical baseline data was slower in animals treated with ATRA, the
      main difference was observed in the test carried out on day 2, p.m. In
      neuroblastoma cells incubated with ATRA, a concentration-dependent increase in
      the expression of COX-2 protein was observed. Changes in the expression of COX-1
      enzyme were not clear. An increase in COX-2 expression in the lumbar spinal cord
      was also observed in animals treated with ATRA. CONCLUSIONS: A clear relationship
      between the oral administration of ATRA and an enhancement of the nociceptive
      withdrawal reflexes was observed in rats. This relationship was associated with
      an increment of the expression of the COX-2 enzyme.

PMID- 15241565
TI  - Ketamine inhibits LPS-induced calcium elevation and NF-kappa B activation in
      monocytes.
AB  - OBJECTIVE: To investigate whether ketamine could inhibit lipopolysaccharide (LPS)
      induced intracellular calcium elevation and NF-kappa B activation in monocytes.
      MATERIALS AND METHODS: Isolated rat monocytes were challenged with 10 microg/ml
      LPS with or without the presence of various concentrations of ketamine (10, 100,
      1000 microM). Intracellular calcium was monitored by laser confocal microscopy.
      NF-kappa B activity of the nuclear extracts of monocytes was analyzed by
      electrophoretic mobility shift assay (EMSA). RESULTS: LPS provoked a significant
      calcium elevation and enhanced NF-kappa B activity in monocytes. Ketamine above
      concentration of 100 microM inhibited endotoxin-induced intracellular calcium
      elevation and NF-kappa B activity. Ketamine itself had no effect on either of
      them. CONCLUSIONS: These findings suggest that ketamine could suppress NF-kappa B
      in monocytes exposed to endotoxin, and this anti-inflammatory effect might act
      through attenuating intracellular calcium elevation.

PMID- 15241566
TI  - The effect of cutaneous mast cell degranulation on sensitivity to heat.
AB  - OBJECTIVE: To determine whether depletion of inflammatory mediators from
      cutaneous mast cells influences cutaneous sensitivity to heat or the thermal
      hyperalgesia provoked by capsaicin or noradrenaline. SUBJECTS: Ten healthy men.
      METHODS AND RESULTS: Compound 48/80 was introduced by iontophoresis into the
      forearm. Wheals at the site of compound 48/80 iontophoresis subsided over four
      pre-treatments, consistent with mast cell degranulation. Flares in the skin
      surrounding the compound 48/80 sites decreased after the first pre-treatment but
      persisted to some extent after wheals had disappeared, suggesting that a reagent
      produced during mast cell activation (e.g., a cytokine or lipoxygenase product
      released from degranulated mast cells) triggered a residual flare. Sensitivity to
      heat increased after the second administration of compound 48/80, possibly due to
      sensitization of thermal nociceptors by inflammatory mediators released from
      infiltrating leukocytes. However, the compound 48/80 pre-treatment inhibited the
      hyperalgesic effect of capsaicin. Pre-treatment with compound 48/80 did not
      prevent axon-reflex vasodilatation to noradrenaline or the hyperalgesic effect of
      noradrenaline in capsaicin-treated skin. CONCLUSIONS: Two mechanisms could
      account for the inhibitory effect of the compound 48/80 pre-treatment on the
      hyperalgesic effect of capsaicin. First, mast cell products could partly mediate
      the hyperalgesic effect of capsaicin. Second, partial desensitization of the
      vanilloid receptor subtype-1 by a reagent produced during mast cell activation
      (e.g., a lipoxygenase product) could mask the hyperalgesic effect of capsaicin.
      Mast cells do not appear to mediate the hyperalgesic effect of noradrenaline.

PMID- 15241567
TI  - Cardiac and regional haemodynamic effects of histamine N-methyltransferase
      inhibitor metoprine in haemorrhage-shocked rats.
AB  - OBJECTIVE AND DESIGN: The increase in central histamine concentrations after
      inhibition of histamine N-methyltransferase (HNMT) activity is associated with
      the reversal of critical haemorrhagic hypotension, therefore the present study
      examines cardiac and regional haemodynamic effects of HNMT inhibitor metoprine in
      haemorrhage-shocked rats. MATERIAL: Cardiovascular parameters were measured in 72
      and central histamine concentrations in 12 male Wistar rats anaesthetised with
      ketamine/xylazine. TREATMENT: Metoprine (5, 15 mg/kg) was administered
      intraperitoneally to normotensive and critically-hypotensive rats with mean
      arterial pressure (MAP) 20-25 mmHg. Haemorrhage-shocked rats were pre-treated
      intracerebroventricularly with histamine H(3) receptor agonist R(-)-alpha
      methylhistamine (10 microg) or saline. METHODS: MAP, heart rate (HR) and cardiac
      and regional haemodynamics were monitored within 2 h after treatment, or to death
      if it occurred earlier. Histamine concentrations were measured using enzyme
      immunoassay. ANOVA followed by Neuman-Keules test, and Fisher's exact test were
      used to compare the results. RESULTS: Bleeding resulted in an extreme decrease in
      cardiac index (CI), an increase in total peripheral resistance index (TPRI) and
      the death of control animals within 30 min. Metoprine induced increases in MAP
      and HR which were significantly higher in hypotensive than in normotensive
      animals. The resuscitating effect of metoprine (15 mg/kg) was associated with a
      rise in CI, a decrease in TPRI, and a 100% survival at 2 h. TPRI changes resulted
      from decreased renal, hindquarters and mesenteric vascular resistance. R(-)-alpha
      methylhistamine inhibited metoprine-induced increases in endogenous histamine
      concentrations in the cerebral cortex (0.89 +/- 0.12 vs. 1.25 +/- 0.29 nmol/g of
      wet tissue; P < 0.05), hypothalamus (4.37 +/- 0.42 vs. 5.74 +/- 0.47 nmol/g of
      wet tissue; P < 0.01) and medulla oblongata (0.39 +/- 0.07 vs. 0.65 +/- 0.28
      nmol/g of wet tissue; P < 0.05), diminished haemodynamic effects and decreased
      the survival rate at 2 h to 33% (P < 0.05 vs. the saline-pre-treated group).
      CONCLUSIONS: The results support the hypothesis that histaminergic system
      activation leads to mobilisation of compensatory mechanisms in haemorrhagic
      hypotension.

PMID- 15241568
TI  - Histamine: its novel role as an endogenous regulator of Con A-dependent T cell
      proliferation.
AB  - OBJECTIVE AND DESIGN: The roles of histamine formed by the macrophage - T
      lymphocyte system were evaluated in the regulation of lymphocyte proliferation
      using mice lacking histamine receptors. METHODS: Mice deficient in histamine type
      1 (H1R), type 2 (H2R) or both receptors were employed to estimate possible
      intervention of the receptors in the histamine-dependent lymphocyte
      proliferation. RESULTS: Histamine was produced de novo by spleen cells. Con A
      dependent T cell proliferation decreased when histamine produced in the culture
      was degraded by the addition of histaminase. The H2R-deficient mice also showed a
      significant decrease in the Con A-dependent T cell proliferation, whereas it was
      not modulated in the H1R-deleted mice. Consistent with the reduction in T cell
      proliferation, there was a significant down-regulation of the production of IL-2,
      a T cell growth factor, in the H2R-deficient mice. Con A-dependent IL-2 synthesis
      was abrogated by the addition of histaminase. CONCLUSION: Con A-dependent T cell
      proliferation is (up)regulated by histamine produced de novo through the H2R,
      suggesting that histamine is a newly found regulator of T cell proliferation.

PMID- 15241569
TI  - Blood flow alterations in TNBS-induced colitis: role of endothelin receptors.
AB  - OBJECTIVES: The aim of the present study was to investigate the time dependent
      changes in hemodynamic parameters and to assess the role of endothelin (ET)
      receptors in trinitrobenzene sulfonic acid (TNBS) induced colitis. MATERIALS:
      Inferior mesenteric artery (IMA) hemodynamics, myeloperoxidase activity (MPO) and
      damage scores were measured immediately or 1, 3, 5 and 14 days after colitis.
      TREATMENTS: Another group of rats received a nonselective ET receptor antagonist
      bosentan (30 mg/kg/day), ET-A receptor antagonist BQ485 (60 microg/rat/day) or ET
      B receptor antagonist BQ788 (60 microg/rat/day) prior to and on the 1st, 2nd and
      3rd days after TNBS administration. RESULTS: IMA flow significantly increased at
      90 min followed by a substantial decrease through days 1-5. Tissue MPO activity
      and macroscopic damage score increased on 1st day after the induction of colitis
      and remained elevated 3, 5 and 14 days following colitis. Treatment with bosentan
      or ET-A receptor antagonist largely prevented the colitis-induced reduction in
      blood flow and tissue injury whereas ET-B receptor antagonist did not attenuate
      tissue injury or reductions in blood flow. CONCLUSIONS: Our results demonstrate
      that time-dependent abnormalities occur in IMA hemodynamics following TNBS
      administration. Our findings also indicate that ET-A receptors but not ET-B
      receptors play an important role in the colonic inflammation following TNBS
      administration.

PMID- 15241570
TI  - The membrane lateral domain approach in the studies of lipid-protein interaction
      of GPI-anchored bovine erythrocyte acetylcholinesterase.
AB  - A novel membrane lateral domain approach was used to test whether the activity of
      the membrane-bound enzyme acetylcholinesterase (AChE) depends on the local
      properties (e.g. local lipid ordering) of bovine erythrocyte-ghost membrane. This
      issue has an additional aspect of interest due to an alternative mode of
      insertion of AChE molecules into the membrane by the glycosylphosphatidylinositol
      (GPI) anchor. In our experiments the lateral domain membrane structure was
      influenced by temperature and by the addition of n-butanol, and was
      quantitatively characterized using the method of EPR spectrum decomposition. The
      activity of AChE was determined by a colorimetric assay in the same samples. The
      results show that the membrane stabilizes the conformation of the membrane-bound
      AChE compared to the isolated AChE. In addition, a correlation was observed
      between the temperature dependence of order parameter of the most-ordered domain
      type and the activity of AChE. Therefore, our findings support the idea that the
      function of GPI proteins can be modulated by the lipid bilayer. Based on the
      assumption that the overall activity of AChE depends on the order parameters of
      particular domain types as well as their proportions, two models for AChE
      activity were introduced. In the first, a random distribution of enzyme molecules
      was proposed, and in the second, localization of enzyme molecules in a single
      (cholesterol-rich) domain type was assumed. Better agreement between measured and
      calculated activity values speaks in favor of the second model.

PMID- 15241572
TI  - Captopril-induced bilateral parotid and submandibular sialadenitis.
AB  - Two cases of sialadenitis following treatment with captopril are described. In
      case 1, an upper chest and facial erythema and dryness of the mouth accompanied
      the swelling of the salivary glands. In case 2, a conjunctival erythema
      accompanied the sialadenitis. None of the patients had previously used captopril,
      and, in both cases, the swelling occurred within the first hour after the drug
      intake; the patients had a complete recovery within a few hours after captopril
      was withdrawn. It is possible that the reported effect was caused by a type-B
      idiosyncratic adverse drug reaction.

PMID- 15241571
TI  - Investigation into the interaction of the bacterial protease OmpT with outer
      membrane lipids and biological activity of OmpT:lipopolysaccharide complexes.
AB  - Outer-membrane proteases T (OmpT) are important defence molecules of Gram
      negative bacteria such as Escherichia coli found in particular in clinical
      isolates. We studied the interaction of OmpT with the membrane-forming lipids
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) from the inner
      leaflet and lipopolysaccharide (LPS) from the outer leaflet of the outer
      membrane. These investigations comprise functional aspects of the protein-lipid
      interaction mimicking the outer-membrane system as well as the bioactivity of
      LPS:OmpT complexes in the infected host after release from the bacterial surface.
      The molecular interaction of the lipids PE, PG, and LPS with OmpT was
      investigated by analysing molecular groups in the lipids originating from the
      apolar region (methylene groups), the interface region (ester), and the polar
      region (phosphates), and by analysing the acyl-chain melting-phase behaviour of
      the lipids. The activity of OmpT and LPS:OmpT complexes was investigated in
      biological test systems (human mononuclear cells and Limulus amoebocyte lysate
      assay) and with phospholipid model membranes. The results show a strong influence
      of OmpT on the mobility of the lipids leading to a considerable fluidization of
      the acyl chains of the phospholipids as well as LPS, and a rigidification of the
      phospholipid, but not LPS head groups. From this, a dominant role of the protein
      on the function of the outer membrane can be deduced. OmpT released from the
      outer membrane still contains slight contaminations of LPS, but its strong
      cytokine-inducing ability in mononuclear cells, which does not depend on the Toll
      like receptors 2 and 4, indicates an LPS-independent mechanism of cell
      activation. This might be of general importance for infections induced by Gram
      negative bacteria.

PMID- 15241573
TI  - Response of human jaw muscles to axial stimulation of a molar tooth.
AB  - The reflexes of the main jaw-closer muscles (masseter and anterior temporalis) on
      both sides of the jaw were investigated using surface electromyography to observe
      reflex activity following mechanical stimulation of the 1st right upper-molar
      tooth at various forces under a number of levels of jaw-muscle activity. As with
      analogous studies performed on the incisor, three distinct reflex events were
      identified in the EMG before the earliest conscious subject reaction: early
      excitation, inhibition and late excitation. However, contrary to observations
      found during studies on the incisor, excitation, not inhibition was the primary
      reflex response. The application of a local anaesthetic block around the
      stimulated molar showed that the primary agents in eliciting the observed
      reflexes were not contained within the periodontium of the stimulated tooth. A
      diminished representation of periodontal mechanoreceptors around the molar teeth
      and more elaborate root structures, hence a more solid connection to the jaw and
      consequently less tooth movement, were deemed the likely reason for the
      distinction between the reflex responses of the incisal and molar regions. In
      addition to the reflex studies, the minimum reaction time of a number of subjects
      was determined to permit the distinction of a reflex event and an event that
      could be a conscious subject reaction. It was found that the reaction time of the
      temporalis muscles was significantly shorter than those of the masseter, while no
      significant difference was found between the left and right sides. Overall, the
      data showed that the presence or absence of background muscle activity and
      subject variability were the main causes of changes in the reflex response,
      provided the level of the stimulus was greater than 3 N. The application of local
      anaesthetic had no impact on the reflexes evoked.

PMID- 15241574
TI  - Transfer of resistance training to enhance rapid coordinated force production by
      older adults.
AB  - The purpose of this study was to examine the capacity of resistance training to
      enhance the rapid and coordinated production of force by older people. Thirty
      adults (> or =60 years) completed a visually guided aiming task that required the
      generation of isometric torque in 2 df about the elbow prior to and following a 4
      week training period. Groups of six participants were allocated to two
      progressive (40-100% maximal voluntary contraction (MVC)) resistance-training
      (PRT) groups, to two constant low-load (10% MVC) training groups (CLO) and to one
      no-training control group. Training movements required the generation of either
      combined flexion and supination (FLESUP), or combined extension and supination
      (EXTSUP). In response to training, target acquisition times in the aiming task
      decreased for all groups; however, both the nature of the training load and the
      training movement influenced the pattern and magnitude of improvements
      (EXTSUP_CLO: 36%, FLESUP_PRT 26%, EXTSUP_PRT 22%, FLESUP_CLO 20%, CONTROL 15%).
      For one group that trained with progressively increasing loads, there arose a
      subsequent decrease in performance in one condition of the transfer task. For
      each group, these adaptations were accompanied by systematic changes in the
      coordination of muscles about the elbow joint, particularly the biceps brachii.

PMID- 15241575
TI  - Altered auditory-tactile interactions in congenitally blind humans: an event
      related potential study.
AB  - It has been shown that stimuli of a task-irrelevant modality receive enhanced
      processing when they are presented at an attended location in space (crossmodal
      attention). The present study investigated the effects of visual deprivation on
      the interaction of the intact sensory systems. Random streams of tactile and
      auditory stimuli were presented at the left or right index finger of congenitally
      blind participants. They had to attend to one modality (auditory or tactile) of
      one side (left or right) and had to respond to deviant stimuli of the attended
      modality and side. While in a group of sighted participants, early event-related
      potentials (ERPs) were negatively displaced to stimuli presented at the attended
      position, compared to the unattended, for both the task-relevant and the task
      irrelevant modality, starting as early as 80 ms after stimulus onset (unimodal
      and crossmodal spatial attention effects, respectively), corresponding crossmodal
      effects could not be detected in the blind. In the sighted, spatial attention
      effects after 200 ms were only significant for the task-relevant modality,
      whereas a crossmodal effect for this late time window was observed in the blind.
      This positive rather than negative effect possibly indicates an active
      suppression of task-irrelevant stimuli at an attended location in space. The
      present data suggest that developmental visual input is essential for the use of
      space to integrate input of the non-visual modalities, possibly because of its
      high spatial resolution. Alternatively, enhanced perceptual skills of the blind
      within the intact modalities may result in reduced multisensory interactions
      ("inverse effectiveness of multisensory integration").

PMID- 15241576
TI  - Bouncing or streaming? Exploring the influence of auditory cues on the
      interpretation of ambiguous visual motion.
AB  - When looking at two identical objects moving toward each other on a two
      dimensional visual display, two different events can be perceived: the objects
      can either be seen to bounce off each other, or else to stream through one
      another. Previous research has shown that the large bias normally seen toward the
      streaming percept can be modulated by the presentation of an auditory event at
      the moment of coincidence. However, previous behavioral research on this
      crossmodal effect has always relied on subjective report. In the present
      experiment, we used a novel experimental design to provide a more
      objective/implicit measure of the effect of an auditory cue on visual motion
      perception. In our study, two disks moved toward each other, with the point of
      coincidence hidden behind an occluder. When emerging from behind the occluder,
      the disks (one red, the other blue) could either follow the same trajectory
      (streaming) or else move in the opposite direction (bouncing). Participants made
      speeded discrimination responses regarding the side from which one of the disks
      emerged from behind the occluder. Participants responded more rapidly on
      streaming trials when no sound was presented and on bouncing trials when the
      sound was presented at the moment of coincidence. These results provide the first
      empirical demonstration of the auditory modulation of an ambiguous visual motion
      display using an implicit/objective behavioral measure of perception.

PMID- 15241578
TI  - Ultra-sensitive fully automated immunoassay for detection of propanil in aqueous
      samples: steps of progress toward sub-nanogram per liter detection.
AB  - The widely-used pesticide propanil is a selective post-emergent general-use
      acetanilide herbicide registered for control of broadleaf and grass weeds in
      rice, small grain, and turf. Because broad application and quite heavy use of
      this herbicide lead to contaminated sites and, consequently, contaminated water,
      immunoanalytical methods with very low limits of detection (LOD) and low limits
      of quantification (LOQ) are becoming increasingly important for environmental
      analysis and, especially, for monitoring drinking-water quality. Environmental
      monitoring of pesticides, hormones, endocrine-disrupting chemicals, and
      antibiotics in aqueous samples (e.g. surface, ground, waste, or drinking water)
      with quite difficult matrices places large demands on chemical analysis.
      Biosensors have suitable characteristics such as efficiency in enabling very
      fast, sensitive, and cost-effective detection. Here we describe the steps of
      progress toward sub-nanogram per liter detection of propanil with a fully
      automated immunoassay. In contrast with common analytical methods such as GC-MS
      or HPLC-MS the biosensor used requires no sample pre-treatment and pre
      concentration. The basis of our sensitive assay is an antibody with a high
      affinity constant toward propanil. During the optimization process, we compared
      different surface modifications (four different immobilized derivatives) and
      reduced the amount of antibody per sample. In fact, optimization of the assay
      resulted in an LOD of 0.6 ng L(-1) and an LOQ of 4.5 ng L(-1) without any sample
      pre-treatment and without pre-concentration. These results for propanil with the
      RIANA instrument, and its improved sensitivity for detection of a single
      pesticide at the low nanogram per liter range, show that biosensors can compete
      with common analytical methods in the field of water analysis.

PMID- 15241579
TI  - Flavonoid binding to a multi-drug-resistance transporter protein: an STD-NMR
      study.
AB  - Flavonoids are well known to inhibit the function of the multi-drug-resistance
      (mdr) transporter by interacting with their ATP binding domains. The precise
      orientation of these molecules inside the ATP binding pocket is still unclear. We
      applied the saturation transfer difference (STD) NMR technique to investigate the
      binding of the flavonoid luteolin and its 7-O-beta-D-glycopyranoside to the
      recombinant nucleotide binding domain (NBD2) of mouse-mdr. First, this NMR
      technique confirmed binding of both ligands to NBD2, as was determined from
      tryptophan fluorescence-quenching experiments. Further, the results suggest
      binding of both luteolin and its 7-O-beta-D-glycopyranoside by their polar groups
      at positions 4, 5, and 3' to the protein.

PMID- 15241580
TI  - The personality of science.

PMID- 15241582
TI  - DpsA protects the human pathogen Burkholderia pseudomallei against organic
      hydroperoxide.
AB  - The human pathogen, Burkholderia pseudomalle, is able to survive and multiply in
      hostile environments such as within macrophages. In an attempt to understand its
      strategy to cope with oxidative stress, the physiological role and gene
      regulation of a nonspecific DNA-binding protein (DpsA) was investigated.
      Expression of dpsA increases in response to oxidative stress through increased
      transcription from the upstream katG (catalase-peroxidase) promoter, which is
      OxyR dependent. dpsA is also transcribed from its own promoter, which is
      activated by osmotic stress in an OxyR-independent manner. DpsA-deficient mutants
      are hypersensitive to tert-butyl hydroperoxide, while overexpression of DpsA
      leads to increased resistance to organic oxidants. B. pseudomallei DpsA can also
      protect Escherichia coli against organic hydroperoxide toxicity. The mechanism of
      DpsA-mediated resistance to organic hydroperoxides was shown to differ from that
      of alkyl hydroperoxide reductase.

PMID- 15241581
TI  - Group I metabotropic glutamate receptors interfere in different ways with
      pentylenetetrazole seizures, kindling, and kindling-related learning deficits.
AB  - LY 367385 (mGluR1) and MPEP (mGluR5), which are group I metabotropic glutamate
      receptor (mGluR) antagonists, were used to investigate their effects on
      pentylenetetrazole (PTZ) seizures, kindling, and kindling-related learning
      deficits. Both substances showed anticonvulsant efficacy against seizures induced
      by lower doses of PTZ (40 mg/kg), but they were ineffective in counteracting
      seizures evoked by higher PTZ doses. When these substances were given in the
      course of kindling induction, LY significantly depressed the progression of
      kindled seizure severity. In contrast, MPEP was ineffective in this experiment.
      Treatment with either LY or MPEP did not modify the reaction to challenge dose of
      PTZ. Kindling results in a worsening of shuttle-box learning. LY improved shuttle
      box learning when administered in the course of kindling development or when
      given prior to the learning experiment. This suggests protective and restorative
      effectiveness. In contrast, MPEP was only effective on the learning performance
      of kindled rats when given prior to the shuttle-box experiment, which
      demonstrates restorative effectiveness. Kindling is associated with an increase
      in glutamate binding. LY counteracted this increase whereas MPEP was ineffective.
      It was concluded that mGluR1 and mGluR5 play a specific role in the convulsive
      component of kindling. The beneficial action of the antagonists on kindling
      induced impairments in shuttle-box learning may be associated with their effect
      on glutamatergic synaptic activity.

PMID- 15241583
TI  - Quantitative ultrasound calcaneus measurements: normative data for the Greek
      population.
AB  - Quantitative ultrasound (QUS) is a peripheral bone densitometry technique that is
      rapidly gaining in popularity, and is widely used worldwide for the assessment of
      skeletal status. This, however, generally occurs in the absence of adequate
      clinical guidelines. As accurate interpretation of the results and correct
      classification in individual fracture risk assessment are of great value, the
      present study was carried out to establish a reference database for calcaneal QUS
      measurements across age group and gender in Greece. A total of 1205 subjects (821
      females and 384 males) from three age groups (409 children, 341 adults and 455
      elderly) were recruited. QUS measurements were performed at the heel with the
      Sahara device, which measures broadband ultrasound attenuation (BUA) and speed of
      sound (SOS), and then combines these variables into a single parameter, the
      quantitative ultrasound index (QUI). Overall, gender-related differences were
      more pronounced among the elderly, while age-related differences were more
      pronounced among females. Elderly men had higher QUS parameters than women of
      peer age, but no major gender differences were observed in children and adults.
      In males, only BUA showed a variation with age, being higher in adult and elderly
      men compared to boys. On the other hand, all QUS parameters varied significantly
      with age in females, the general trends being mildly positive from childhood to
      adulthood, when peak levels were observed, and negative thereafter. The results
      for the Greek population were in the range reported previously for other
      populations, but some discrepancies were evident, probably resulting from ethno
      specific characteristics and different QUS instrumentation. Importantly, using
      the manufacturer's or the local database as the reference population for
      computing T-scores led to significantly different classification of subjects into
      conventional categories of risk. These data could be useful as a guide for
      comparing the results of individual studies, as well as for the assessment of
      Greek men and women at risk of fracture.

PMID- 15241584
TI  - The impact of the use of multiple risk indicators for fracture on case-finding
      strategies: a mathematical approach.
AB  - The value of bone mineral density (BMD) measurements to stratify fracture
      probability can be enhanced in a case-finding strategy that combines BMD
      measurement with independent clinical risk indicators. Putative risk indicators
      include age and gender, BMI or weight, prior fracture, the use of
      corticosteroids, and possibly others. The aim of the present study was to develop
      a mathematical framework to quantify the impact of using combinations of risk
      indicators with BMD in case finding. Fracture probability can be expressed as a
      risk gradient, i.e. a relative risk (RR) of fracture per standard deviation (SD)
      change in BMD. With the addition of other continuous or categorical risk
      indicators a continuous distribution of risk indicators is obtained that
      approaches a normal distribution. It is then possible to calculate the risk of
      individuals compared with the average risk in the population, stratified by age
      and gender. A risk indicator with a gradient of fracture risk of 2 per SD
      identified 36% of the population as having a higher than average fracture risk.
      In individuals so selected, the risk was on average 1.7 times that of the general
      population. Where, through the combination of several risk indicators, the
      gradient of risk of the test increased to 4 per SD, a smaller proportion (24%)
      was identified as having a higher than average risk, but the average risk in this
      group was 3.1 times that of the population, which is a much better performance.
      At higher thresholds of risk, similar phenomena were found. We conclude that,
      whereas the change of the proportion of the population detected to be at high
      risk is small, the performance of a test is improved when the RR per SD is
      higher, indicated by the higher average risk in those identified to be at risk.
      Case-finding strategies that combine clinical risk indicators with BMD have
      increased efficiency, while having a modest impact on the number of individuals
      requiring treatment. Therefore, the cost-effectiveness is enhanced.

PMID- 15241585
TI  - A new significant and independent risk factor for falls in elderly men and women:
      a low creatinine clearance of less than 65 ml/min.
AB  - OBJECTIVES: Because impaired renal function is detrimental for the conversion of
      calcidiol to calcitriol (D-hormone) and since D-hormone analogues have been shown
      to decrease the risk of falls, we investigated whether creatinine clearance
      (CrCl) is associated with the number of fallers and falls in elderly men and
      women. METHODS: Within a randomized controlled study, we observed for 36 weeks
      186 placebo-treated community-dwelling elderly men and women over 70, in an
      attempt to determine the influence of baseline CrCl on calcitropic hormone serum
      levels, as well as the influence of baseline CrCl on the number of fallers and
      falls over time. With the help of questionnaires, we regularly assessed fall
      incidence and frequency. The risk of falls and the risk of becoming a faller were
      assessed in multivariate-controlled logistic regression models according to a
      cutoff value of the CrCl set at 65 ml/min. RESULTS: At baseline, serum levels of
      1.25(OH)(2)D(3) and iPTH were, in multivariate-controlled analyses, significantly
      associated with CrCl (p<0.0001, p=0.001, respectively), whereas serum levels of
      25(OH)D(3) were not associated with CrCl. Below a CrCl of 65 ml/min,
      1.25(OH)(2)D(3) serum levels steadily declined. We therefore chose a CrCl of 65
      ml/min as cutoff for further analyses. During the 36 weeks of observation,
      elderly people with a CrCl of < 65 ml/min had, in multivariate controlled
      analyses, compared with elderly with a CrCl of > or =65 ml/min, a significantly
      higher incidence of number of fallers (25/70 vs 21/116; OR=4.01; 95% CI, 1.48
      10.98; p=0.006), and a significantly higher incidence of falls (28/70 vs 23/116;
      OR=3.68; 95% CI, 1.38-9.82; p=0.009). CONCLUSIONS: For the first time we showed
      that in a community-dwelling population of elderly men and women, a CrCl of less
      than 65 ml/min is a significant and independent risk factor for fallers and
      falls.

PMID- 15241587
TI  - Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in
      28 patients.
AB  - OBJECTIVE: To evaluate anion and osmolal gaps as diagnostic tools in methanol
      poisoning. DESIGN AND SETTING: Clinical observational study. PATIENTS AND
      METHODS: In a recent methanol outbreak, the initial triage and treatment
      decisions in 28 patients were based mainly upon the values of the osmolal and
      anion gaps on admission. Methanol and formate levels were later compared to these
      gaps by linear regression analysis. RESULTS: The correlation between the osmolal
      gaps and serum methanol concentrations on admission was linear (y = 1.03x+12.71,
      R2 = 0.94). The anion gaps correlated well with the serum formate concentrations
      (y = 1.12x+13.82, R2 = 0.86). Both gaps were elevated in 24 of the 28 subjects
      upon admission. Three patients had an osmolal gap within the reference area
      (because of low serum methanol), but elevated anion gap because of formate
      accumulation. One patient with probable concomitant ethanol ingestion had a high
      osmolal gap and a normal anion gap. CONCLUSION: Osmolal and anion gaps are useful
      in the diagnosis and triage of methanol-exposed subjects. Confounders are low
      serum methanol and concomitant ethanol ingestion.

PMID- 15241586
TI  - Role of 5-lipoxygenase in the multiple organ failure induced by zymosan.
AB  - OBJECTIVE: This study investigated the role of 5-lipoxygenase in the pathogenesis
      of multiple organ failure (MOF) induced by zymosan. DESIGN: Male mice with a
      targeted disruption of the 5-lipoxygenase gene (5-LOKO) and littermate wild-type
      (WT) controls (5-LOWT) were used to evaluate the role of 5-lipoxygenase (5-LO) in
      the pathogenesis of MOF. SETTING: University research laboratory. INTERVENTIONS
      AND MEASUREMENTS: MOF was induced by peritoneal injection of zymosan (500 mg/kg
      i.p. as a suspension in saline) in 5-LOWT and in 5-LOKO mice. MOF was assessed 18
      h after administration of zymosan and monitored for 12 days (for loss of body
      weight and mortality). RESULTS: A severe inflammatory process induced by zymosan
      administration in WT mice coincided with the damage of lung and small intestine,
      as assessed by histological examination. Myeloperoxidase activity indicative of
      neutrophil infiltration and lipid peroxidation were significantly increased in
      zymosan-treated WT mice. Zymosan in the WT mice also induced a significant
      increase in the plasma level of nitrite/nitrate. Immunohistochemical examination
      demonstrated a marked increase in the immunoreactivity to ICAM-1 and P-selectin
      in the lung and intestine of zymosan-treated WT mice. In contrast, the degree of
      (a) peritoneal inflammation and tissue injury, (b) upregulation/expression of P
      selectin and ICAM-1, and (c) neutrophil infiltration were markedly reduced in
      intestine and lung tissue obtained from zymosan-treated 5-LO deficient mice.
      Zymosan-treated 5-LOKO showed also a significantly decreased mortality.
      CONCLUSIONS: These findings clearly demonstrate that 5-LO exerts a role in
      zymosan-induced nonseptic shock.

PMID- 15241588
TI  - Recovery from lung injury in survivors of acute respiratory distress syndrome:
      difference between pulmonary and extrapulmonary subtypes.
AB  - OBJECTIVE: To determine whether long-term outcome differs between acute
      respiratory distress syndrome (ARDS) resulting from pulmonary (ARDSp) and
      extrapulmonary (ARDSexp) causes. DESIGN: Observational study. SETTING: Medical
      intensive care unit of a university hospital. PATIENTS: Twenty-nine ARDS patients
      (16 ARDSp and 13 ARDSexp) who survived over 6 months after diagnosis.
      MEASUREMENTS AND RESULTS: The two groups did not differ according to demographic
      data and severity indices on admission. The duration of ICU stay (median 21 days
      [interquartile range, 12-43 days] vs 12 [6.5-20] days, p=0.097) tended to be
      longer and total ventilation time (360 [96-700] h vs 144 [42.5-216] h, p=0.045)
      were longer in the patients with ARDSp. The ARDSp patients showed more severe
      abnormalities on thin-section computed tomography (CT), including ground-glass
      opacity (GGO; 6 [3-16] vs 0 [0-2.5], p=0.002), reticular density (12 [8-14] vs 5
      [2-9], p=0.033) and the sum of all four patterns of lesion (20 [11-27] vs 5 [2
      12], p=0.006). There were no between-group differences in Spitzer's Quality of
      Life index and the Chronic Respiratory Questionnaire. CONCLUSIONS: These results
      suggest that ARDSp would leave more severe lung sequelae than ARDSexp, but the
      clinical relevance of their difference is questionable.

PMID- 15241589
TI  - [The upper extremity in cerebral palsy. OP indications and surgical techniques].
AB  - In cerebral palsy patients, surgical treatment procedures of the upper extremity
      have an important place in the concept of multidisciplinary care. Nevertheless,
      operative indications remain selective and the number of operative interventions
      is limited in comparison to the lower extremity. For an appropriate surgical
      outcome, soft tissue techniques, applied in a multilevel strategy with clear
      consideration of functional aspects, are often sufficient. Osseous operative
      corrections, i.e. osteotomies or joint fusions, are restricted to selected cases.
      The retrospective evaluation of 209 patients who underwent surgical treatment of
      the upper extremity between 1975 and 2000 revealed a general satisfaction with
      the functional outcome in 68.4% of cases and cosmetic improvement in 97.6% of
      cases. The surgical treatment of upper limb deformities in cerebral palsy
      requires a particular focus on the correct indication and selection of an
      adequate surgical technique requiring outstanding experience.

PMID- 15241590
TI  - [Nanoparticulate silver. A new antimicrobial substance for bone cement].
AB  - BACKGROUND: Multiresistant bacteria have become an important problem in
      prosthetic joint infections. Their frequent resistance against gentamicin, which
      is commonly used in antibiotic-loaded bone cements, makes a new prophylaxis
      necessary. METHODS: PMMA-cement was loaded with 1% nanoparticulate silver and its
      antibacterial activity tested in vitro against gentamicin-resistant MRSE and MRSA
      strains as well as being compared to the activity of plain and gentamicin-loaded
      bone cements. A quantitative elution testing was also done to study the
      potentially cytotoxic effects of NanoSilver cement. RESULTS: Unloaded and PMMA
      cement loaded with 2% gentamicin did not exhibit any antibacterial activity
      against MRSE and MRSA. At 1%, NanoSilver cement completely inhibited the
      proliferation of MRSA and MRSE. NanoSilver bone cement did not show any
      significant differences compared to the non-toxic control group. CONCLUSIONS: If
      these promising in vitro results can be confirmed in vivo, NanoSilver bone cement
      may be of considerable value in total joint arthroplasty.

PMID- 15241591
TI  - [Shoulder instability. Classification and treatment].
AB  - Shoulder instability includes different degrees of instability from painful
      hyperlaxity to subluxation to dislocation. Different classifications of shoulder
      instability have been created in order to facilitate decision making for
      treatment. None of these, however, has gained acceptance. Subject to the
      indications, shoulder instability can be treated conservatively or surgically
      after repositioning the acute dislocation. A survey of arthroscopic and open
      stabilization procedures and their results are given in relation to the
      indications.

PMID- 15241592
TI  - Plasma insulin and cardiovascular mortality in non-diabetic European men and
      women: a meta-analysis of data from eleven prospective studies.
AB  - AIMS/HYPOTHESIS: We examined the association between plasma insulin and
      cardiovascular mortality in non-diabetic European men and women based on data
      from eleven prospective studies. METHODS: The study population comprised 6156 men
      and 5351 women aged 30-89 years. Baseline measurements included oral glucose
      tolerance test, fasting and 2-h plasma insulin, and conventional risk factors.
      Cox models were used to calculate hazard ratios (HRs) and their 95% confidence
      intervals, and overall HRs were assessed by meta-analyses. RESULTS: During the
      8.8-year follow-up, 362 men and 70 women died from cardiovascular disease. The
      age- and smoking-adjusted overall HR of cardiovascular mortality for the highest
      vs the lower quartiles of fasting insulin was 1.58 (95% CI: 1.26-1.97) in men and
      2.64 (1.54-4.51) in women. Adjusting for other risk factors in addition, the HR
      was 1.54 (1.16-2.03) in men and 2.66 (1.45-4.90) in women. For 2-h insulin these
      HRs were 1.28 (0.99-1.66), 1.87 (0.87-4.02), and 0.85 (0.60-1.21), 1.36 (0.53
      3.45). The overall HRs for interquartile ranges for fasting and 2-h insulin, with
      full adjustment, were 1.13 (1.05-1.22) and 1.11 (1.01-1.23) in men, and 1.25
      (1.08-1.45) and 1.11 (0.91-1.36) in women. CONCLUSIONS/INTERPRETATION:
      Hyperinsulinaemia, defined by the highest quartile cut-off for fasting insulin,
      was significantly associated with cardiovascular mortality in both men and women
      independently of other risk factors. Associations between high 2-h insulin and
      cardiovascular mortality were weaker and non-significant. Weak positive
      associations of fasting and 2-h insulin with cardiovascular mortality over
      interquartile ranges were, however, more similar.

PMID- 15241594
TI  - Does WHI tell us how to prevent diabetes?

PMID- 15241593
TI  - Interleukin-6 and insulin sensitivity: friend or foe?

PMID- 15241595
TI  - Microsatellite genetic linkage maps of myrobalan plum and an almond-peach hybrid-
      location of root-knot nematode resistance genes.
AB  - Inheritance and linkage studies were carried out with microsatellite [or simple
      sequence repeat (SSR)] markers in a F(1) progeny including 101 individuals of a
      cross between Myrobalan plum ( Prunus cerasifera Ehrh) clone P.2175 and the
      almond (Prunus dulcis Mill.)-peach ( Prunus persica L. Batsch) hybrid clone GN22
      ["Garfi" (G) almond x "Nemared" (N) peach]. This three-way interspecific Prunus
      progeny was produced in order to associate high root-knot nematode (RKN)
      resistances from Myrobalan and peach with other favorable traits for Prunus
      rootstocks from plum, peach and almond. The RKN resistance genes, Ma from the
      Myrobalan plum clone P.2175 and R(MiaNem) from the 'N' peach, are each
      heterozygous in the parents P.2175 and GN22, respectively. Two hundred and
      seventy seven Prunus SSRs were tested for their polymorphism. One genetic map was
      constructed for each parent according to the "double pseudo-testcross" analysis
      model. The Ma gene and 93 markers [two sequence characterized amplified regions
      (SCARs), 91 SSRs] were placed on the P.2175 Myrobalan map covering 524.8 cM. The
      R(MiaNem) gene, the Gr gene controlling the color of peach leaves, and 166
      markers (one SCAR, 165 SSRs) were mapped to seven linkage groups instead of the
      expected eight in Prunus. Markers belonging to groups 6 and 8 in previous maps
      formed a single group in the GN22 map. A reciprocal translocation, already
      reported in a G x N F(2), was detected near the Gr gene. By separating markers
      from linkage groups 6 and 8 from the GN22 map, it was possible to compare the
      eight homologous linkage groups between the two maps using the 68 SSR markers
      heterozygous in both parents (anchor loci). All but one of these 68 anchor
      markers are in the same order in the Myrobalan plum map and in the almond-peach
      map, as expected from the high level of synteny within Prunus. The Ma and
      R(MiaNem)genes confirmed their previous location in the Myrobalan linkage group 7
      and in the GN22 linkage group 2, respectively. Using a GN22 F(2) progeny of 78
      individuals, a microsatellite map of linkage group 2 was also constructed and
      provided additional evidence for the telomeric position of R(MiaNem) in group 2
      of the Prunus genome.

PMID- 15241596
TI  - Introgression molecular analysis of a leaf rust resistance gene from Coffea
      liberica into C. arabica L.
AB  - Leaf rust caused by the fungus Hemileia vastatrix is the most devastating disease
      of arabica coffee ( Coffea arabica). Therefore, developing leaf rust-resistant
      varieties has been a breeding objective of the highest priority in many
      countries. The purpose of the present work was to gain insight into the mechanism
      of introgression into C. arabica of a leaf rust resistance gene from C. liberica
      (i.e. S(H)3 resistance factor) and to identify associated molecular markers. An
      F(2) progeny (i.e. 101 individuals) derived from a cross between Matari, an
      arabica accession and liberica-introgressed line S.288, was evaluated for
      resistance against three different races of H. vastatrix. The progeny segregated
      for the S(H)3 gene in a 3:1 ratio, as expected for a single dominant gene.
      Amplified fragment length polymorphism analysis of a population subset using 80
      different primer combinations revealed that at least half of the total
      polymorphism observed in the population is associated with introgression of C.
      liberica chromosome fragments. Furthermore, 15 primer combinations generating
      candidate marker bands associated with the S(H)3 resistance gene were used to
      analyse the whole F(2) population. A total of 34 marker bands originating from
      S.288 and attributable to introgression were scored. None exhibited segregation
      distortion. Linkage analysis revealed only three distinct introgressed fragments
      corresponding to a total length of 52.8 cM. Twenty-one markers were strongly
      associated (LOD score >14) with the S(H)3 gene and were grouped together in a
      single linkage group of 6.3 cM. The results are discussed in relation to the
      efficient use of genetic resources in arabica breeding.

PMID- 15241597
TI  - Genetic pathways and new progression markers for prostate cancer defined by
      microsatellite allelotyping.
AB  - A prospective study was carried out on a large cohort of males undergoing radical
      retropubic prostatectomy in order to identify genetic marker regions
      significantly associated with tumor formation. By comprehensive allotyping of
      chromosomes known to be associated with prostate carcinogenesis, an algorithm
      could be formulated for the genetic pathway and a method of discrimination
      between aggressive and less aggressive forms could be identified.

PMID- 15241598
TI  - [Preoperative imaging as the basis for image-guided neurosurgery].
AB  - With the progressive development of soft- and hardware, the acceptance of image
      guided neurosurgery has increased dramatically. Additional image data are
      required to analyze the nature and the dimensions of pathological processes and
      the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special
      modalities of CT and MR imaging, are routinely used. Secondary post-processing
      options are used to detect intracerebral lesions as well as adjacent functional
      eloquent regions in the parenchymatous organ pre- and intraoperatively. The
      integration of different image information guarantees the precise planning and
      realization of surgical maneuvers. The segmentation of interesting structures and
      risk structures, as well as their implementation in the neuronavigation systems,
      help to avoid additional intraoperative traumatization and offer a higher level
      of safety and precision. In this article the value and limitations of presurgical
      imaging will be discussed.

PMID- 15241599
TI  - [Percutaneous laser-induced thermotherapy of lung metastases: experience gained
      during 4 years].
AB  - We perform laser ablation of lung metastases for four years. In the following we
      report on technical success, ablation results and follow-up. 30 patients with a
      total of 42 lung metastases were treated. Patients were aged between 42 and 74
      years. Primary tumors were mostly colorectal carcinomas, head and neck and uro
      genital tumors. Technical success was achieved in 40, complete ablation in 14
      metastases (33%); however, in 8 metastases follow-up was too short for a valid
      evaluation (4-8 weeks). Further analysis may improve the overall results:
      metastases located in the central parts of the lungs were more easily treated
      than those located peripherally, best results were achieved in metastases not
      larger than 3 cm, percutaneous ablation of lung metastases has potential as an
      additional therapeutic option if surgery is not possible.

PMID- 15241600
TI  - [Lithium intoxication mimics Alzheimer's disease in PET and clinical findings].
AB  - To improve specificity and sensitivity in the diagnosis of Alzheimer's disease,
      neuropsychological tests and fluorine-18-FDG-PET are increasingly used. Here we
      present a patient whose lithium intoxication mimicked Alzheimer's disease both
      clinically and in 18-FDG-PET. This case serves as a reminder of the importance of
      the differential diagnosis of dementias and is intended to highlight one
      potential pitfall.

PMID- 15241601
TI  - [Pathological gambling. An empirical study of the desire for addictive
      substances].
AB  - Drug craving, the irresistible urge for drug intake, is being discussed as a
      central construct for the explanation of addictive behaviour and for relapses so
      far only in substance-related addiction. Based on learning models for the
      maintenance of addiction, in this study, cue-induced craving and psychological
      variables that influence craving were investigated in subjects with excessive
      rewarding behaviour such as pathological gambling. Based on the cue-reactivity
      paradigm, pathological gamblers and healthy controls were exposed to gambling and
      other cues. Emotional processing of the gambling cues, cue-induced craving, and
      the influence on craving of depression, anxiety, and stress-coping strategies
      were investigated. The results demonstrate disorder-specific processing of cues
      in pathological gamblers, even after abstinence for more than a year. In
      addition, craving is influenced by psychological disabilities. Data are discussed
      with respect to comparable data in studies about substance-related addicts.

PMID- 15241602
TI  - Ernst Mayr: the doyen of twentieth century evolutionary biology.

PMID- 15241603
TI  - The modern theory of biological evolution: an expanded synthesis.
AB  - In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently
      proposed natural selection as the basic mechanism responsible for the origin of
      new phenotypic variants and, ultimately, new species. A large body of evidence
      for this hypothesis was published in Darwin's Origin of Species one year later,
      the appearance of which provoked other leading scientists like August Weismann to
      adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of
      evolution was further elaborated, most notably in a series of books by Theodosius
      Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first
      summarize the history of life on Earth and provide recent evidence demonstrating
      that Darwin's dilemma (the apparent missing Precambrian record of life) has been
      resolved. Next, the historical development and structure of the "modern
      synthesis" is described within the context of the following topics: paleobiology
      and rates of evolution, mass extinctions and species selection, macroevolution
      and punctuated equilibrium, sexual reproduction and recombination, sexual
      selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary
      developmental biology, phenotypic plasticity, epigenetic inheritance and
      molecular evolution, experimental bacterial evolution, and computer simulations
      (in silico evolution of digital organisms). In addition, we discuss the expansion
      of the modern synthesis, embracing all branches of scientific disciplines. It is
      concluded that the basic tenets of the synthetic theory have survived, but in
      modified form. These sub-theories require continued elaboration, particularly in
      light of molecular biology, to answer open-ended questions concerning the
      mechanisms of evolution in all five kingdoms of life.

PMID- 15241604
TI  - The species flocks of East African cichlid fishes: recent advances in molecular
      phylogenetics and population genetics.
AB  - With more than 3,000 species, the fish family Cichlidae is one of the most
      species-rich families of vertebrates. Cichlids occur in southern and central
      America, Africa, Madagascar, and India. The hotspot of their biodiversity is East
      Africa, where they form adaptive radiations composed of hundreds of endemic
      species in several lakes of various sizes and ages. The unparalleled species
      richness of East African cichlids has been something of a conundrum for
      evolutionary biologists and ecologists, since it has been in doubt whether these
      hundreds of species arose by allopatric speciation or whether it is necessary to
      invoke somewhat less traditional models of speciation, such as micro-allopatric,
      peripatric, or even sympatric speciation or evolution through sexual selection
      mediated by female choice. Ernst Mayr's analyses of these evolutionary uniquely
      diverse species assemblages have contributed to a more direct approach to this
      problem and have led to a deeper understanding of the patterns and processes that
      caused the formation of these huge groups of species. We review here recent
      molecular data on population differentiation and phylogenetics, which have helped
      to unravel, to some extent, the patterns and processes that led to the formation
      and ecological maintenance of cichlid species flocks. It is becoming apparent
      that sexually selected traits do play an important role in speciation in micro
      allopatric or even sympatric settings. Species richness seems to be roughly
      correlated with the surface area, but not the age, of the lakes. We observe that
      the oldest lineages of a species flock of cichlids are often less species-rich
      and live in the open water or deepwater habitats. While the species flocks of the
      Lake Malawai and the Lake Victoria areas were shown to be monophyletic, the
      cichlid assemblage of Lake Tanganyika seems to consist of several independent
      species flocks. Cichlids emerge as an evolutionary model system in which many
      fundamental questions in evolution and ecology can be tested successfully, yet
      for other fish species flocks the relative importance of alternative mechanisms
      of speciation is likely to differ from that in cichlid fish.

PMID- 15241605
TI  - Multilevel selection and social evolution of insect societies.
AB  - How sterile, altruistic worker castes have evolved in social insects and how they
      are maintained have long been central topics in evolutionary biology. With the
      advance of kin selection theory, insect societies, in particular those of
      haplodiploid bees, ants, and wasps, have become highly suitable model systems for
      investigating the details of social evolution and recently also how within-group
      conflicts are resolved. Because insect societies typically do not consist of
      clones, conflicts among nestmates arise, for example about the partitioning of
      reproduction and the allocation of resources towards male and female sexuals.
      Variation in relatedness among group members therefore appears to have a profound
      influence on the social structure of groups. However, insect societies appear to
      be remarkably robust against such variation: division of labor and task
      allocation are often organized in more or less the same way in societies with
      high as in those with very low nestmate relatedness. To explain the discrepancy
      between predictions from kin structure and empirical data, it was suggested that
      constraints-such as the lack of power or information-prevent individuals from
      pursuing their own selfish interests. Applying a multilevel selection approach
      shows that these constraints are in fact group-level adaptation preventing or
      resolving intracolonial conflict. The mechanisms of conflict resolution in insect
      societies are similar to those at other levels in the biological hierarchy (e.g.,
      in the genome or multicellular organisms): alignment of interests, fair lottery,
      and social control. Insect societies can thus be regarded as a level of selection
      with novelties that provide benefits beyond the scope of a solitary life.
      Therefore, relatedness is less important for the maintenance of insect societies,
      although it played a fundamental role in their evolution.

PMID- 15241606
TI  - [Multidirectional atlantoaxial instability of an os odontoideum in an adult].
AB  - Increasing neck pain in a 29 year old woman after a frontal car collision gave
      reason for a conventional x-ray that presented a traumatically displaced os
      odontoideum positioned at the top of the dens axis. No neurological defect was
      seen. Dynamic flexion/extension film showed a movement to an atlantoaxial
      dislocation with a shift of the os odontoideum. The sclerotic structure of the
      corresponding bony surfaces was confirmed by computed tomography, whereas
      magnetic resonance imaging demonstrated a posttraumatic signal change in front of
      the base of dens axis and os odontoideum. Fusion was achieved by computed
      navigation with C1/C2 transfacetal screws as described by Magerl and interspinal
      fusion with a bicortical autologous iliac crest graft and a posterior tension
      band as described by Brooks. An exact positioning of screws past the asymmetric
      course of both arteria vertebrales was possible by navigation. The patient was
      free of pain 5 months after the fusion.

PMID- 15241607
TI  - [Application of low intensity, pulsed ultrasound on distraction osteogenesis of
      the humerus. Case report].
AB  - Low intensity pulsed ultrasound accelerates fracture healing both clinically and
      experimentally. Based on recently published animal studies, an improvement in
      regenerative bone maturation after distraction osteogenesis due to low intensity,
      pulsed ultrasound is also expected. We report on an 18 year-old female patient
      suffering from an acquired shortening of the right upper arm of 10 cm after
      humeral osteitis as a baby. The patient was admitted to hospital for corticotomy
      and distraction osteogenesis at the afflicted humerus. Due to the published
      experimental results in animals which indicate an improvement in bone
      regeneration during callotasis with the additional application of low intensity,
      pulsed ultrasound, we decided to try this procedure. The calculated distraction
      consolidation index was 21 days/cm, which is below the mean of 30 days/cm
      reported in the literature for humeral lengthening by distraction osteogenesis.
      The calculated healing index according to Paley was 0.7 months/cm in our patient.
      Compared to reference data, in which a range of from 0.87 months/cm to 1.5
      months/cm is reported, our patient showed an accelerated maturation of
      distraction callus. The duration of treatment of the patient was clearly
      shortened by the additional application of low intensity, pulsed ultrasound. If
      distraction osteogenesis is correctly indicated, the early use of low intensity,
      pulsed ultrasound should be considered, since an acceleration of callus formation
      with consecutive shortening of treatment time could be attained while wearing an
      external fixator, leading to a decrease in cumulative complications, such as pin
      tract infections. Further studies from our research group regarding this topic
      will follow.

PMID- 15241608
TI  - A preliminary optical and electron microscopic study of the beta(1) integrin
      distribution pattern of human osteosarcoma-derived cells.
AB  - Immunogold labelling was used to study the organisation of the beta(1) integrins
      on osteosarcoma-derived osteoblasts (Saos-2 and MG-63). Monolayers of cells were
      prepared in multiwell culture plates on both uncovered and collagen-covered
      coverslips, and beta(1) integrins were primarily labelled using mouse monoclonal
      antibodies to beta(1) integrins. Indirect immunofluorescence labels using an anti
      mouse fluorescein-conjugated goat antibody showed an even distribution of the
      beta(1) integrins on the cell membranes of all cell types used. A concentration
      of 2 microg/ml of the primary antibodies and a 1:100 dilution of the secondary
      antibodies were determined as the optimal concentration for labelling to use with
      indirect localisation of the primary antibodies gold conjugated to goat anti
      mouse antibodies and viewed under an electron microscope. Ten nanometre gold
      particles were used for transmission electron microscopy (TEM) and 40 nm gold
      particles for scanning electron microscopy. TEM showed that beta(1) integrins
      were mainly clustered on the cell membrane processes with less labelling on the
      cell membranes themselves. The distribution of beta(1) integrins on osteosarcoma
      cells supports the concept that integrins may function by forming focal adhesions
      at the site of the cytoplasmic membrane processes.

PMID- 15241610
TI  - The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in
      glaucoma patients: a double-masked placebo-controlled clinical study.
AB  - BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate
      the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total
      outflow facility in human glaucomatous eyes. METHODS: In a randomized double
      blind clinical study patients with POAG and OHT receive either Latanoprost 0.005%
      or placebo once in the evening. Fluorophotometry (Fluorotron Master II,
      Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10
      patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out
      period all patients received a systemic antiglaucomatous therapy (Acetazolamide)
      up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg
      at baseline were excluded. Fluorophotometry, tonography and IOP were measured at
      baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's
      paired t test. RESULTS: All patients completed the protocol. The IOP
      significantly decreased (25%) after 1 and 2 weeks of treatment with
      Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow
      over time in both groups. Although tonographic mean C values in both groups did
      not show any difference over time, the estimated total outflow facility C
      (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2
      weeks. A significant difference of outflow co-efficient correlated to normal
      pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05).
      CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in
      IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow
      values in both groups showed no increase or decrease in aqueous humor dynamics as
      proved in many previous studies. The known effect of Latanoprost increase
      uveoscleral outflow by remodeling extracellular matrix and widening intermuscular
      spaces in the ciliary body may not detected by pneumotonography after 2 weeks of
      treatment. The significant increase in estimated total outflow facility (Goldmann
      formula) in latanoprost-treated eyes and the decrease of IOP took place at
      constant flow rates. The increase in conventional outflow facility may indicate
      trabecular meshwork changes, but it cannot explain the significant decrease in
      IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the
      major role as considered in many previous studies.

PMID- 15241612
TI  - Sub-50-fs laser retinal damage thresholds in primate eyes with group velocity
      dispersion, self-focusing and low-density plasmas.
AB  - BACKGROUND: In vivo retinal injury studies using sub-50-femtosecond laser pulses
      in the near-infrared must consider nonlinear effects such as group velocity
      dispersion (GVD), self-focusing, laser-induced breakdown (LIB) and low-density
      plasmas (LDPs). In this paper we present the results of our theoretical
      calculations of nonlinear effects and our experimental measurements for the
      visible lesion thresholds in live eyes. We compare these values with the measured
      LIB and LDP thresholds in an artificial eye. All three thresholds were measured
      with and without pre-chirping the input pulse to compensate for GVD effects.
      METHODS: We recorded the minimum visible lesion (MVL) thresholds in vivo for sub
      50-fs laser pulses, with and without pre-chirping the input pulses. In addition,
      we measured the LIB and LDP thresholds, with and without pre-chirping, within an
      artificial eye. Different degrees of pre-chirping were required to give optimal
      compensation for GVD in the live eye and the artificial eye. Probit analysis was
      used on all data, and comparisons among thresholds were made, to determine the
      effects on the three thresholds of chirp compensation for GVD. RESULTS: Results
      of our nonlinear modeling and calculations for GVD compensation, self-focusing,
      LIB, and low-density plasmas were compared with our experimental results using
      live eyes and the artificial eye. The damage threshold in live eyes dropped in
      energy from 0.25 microJ, for the flat-phase input, to 0.17 microJ when optimally
      chirped pulses were used, while the LIB threshold was reduced from 0.29 microJ to
      0.19 microJ with optimally chirped pulses. The LDP threshold dropped from 0.21
      microJ to 0.14 microJ with the pre-chirped pulse. At 44 fs, these energies
      produced peak powers at least twice the calculated critical power that produces
      nonlinear self-focusing and beam collapse, for propagation of non-aberrated
      gaussian beams in a uniform medium. CONCLUSIONS: Based on our measurements of the
      MVL thresholds, with and without GVD compensation, we conclude that the visible
      lesion thresholds produced by 44 fs pulses in rhesus eyes are increased in energy
      due to GVD. The MVL ED50 was reduced by one third when the pulse was pre-chirped
      to compensate for GVD in the eye. This reduction in amplitude also holds true in
      the artificial eye for the LIB ED50 bubble thresholds and the LDP ED50 plasma
      channels, when using pre-chirped pulses versus non-chirped pulses. We also
      conclude from the data presented that low-density plasmas, and not LIB cavitation
      bubbles, are the probable mediating factor at the visible lesion thresholds
      observed within live eyes, for pulse durations at and below 50 fs. Therefore, the
      plasma channel created by LDPs is the major damage mechanism, if not the only
      damage mechanism, at MVL threshold energies for these pulse durations.

PMID- 15241609
TI  - Mammalian peroxisomes and reactive oxygen species.
AB  - The central role of peroxisomes in the generation and scavenging of hydrogen
      peroxide has been well known ever since their discovery almost four decades ago.
      Recent studies have revealed their involvement in metabolism of oxygen free
      radicals and nitric oxide that have important functions in intra- and
      intercellular signaling. The analysis of the role of mammalian peroxisomes in a
      variety of physiological and pathological processes involving reactive oxygen
      species (ROS) is the subject of this review. The general characteristics of
      peroxisomes and their enzymes involved in the metabolism of ROS are briefly
      reviewed. An expansion of the peroxisomal compartment with proliferation of
      tubular peroxisomes is observed in cells exposed to UV irradiation and various
      oxidants and is apparently accompanied by upregulation of PEX genes. Significant
      reduction of peroxisomes and their enzymes is observed in inflammatory processes
      including infections, ischemia-reperfusion injury, and allograft rejection and
      seems to be related to the suppressive effect of tumor necrosis factor-alpha on
      peroxisome function and peroxisome proliferator activated receptor-alpha.
      Xenobiotic-induced proliferation of peroxisomes in rodents is accompanied by the
      formation of hepatic tumors, and evidently the imbalance in generation and
      decomposition of ROS plays an important role in this process. In PEX5-/- knockout
      mice lacking functional peroxisomes severe alterations of mitochondria in various
      organs are observed which seem to be due to a generalized increase in oxidative
      stress confirming the important role of peroxisomes in homeostasis of ROS and the
      implications of its disturbances for cell pathology.

PMID- 15241611
TI  - A 6-month randomized clinical trial of bimatoprost 0.03% versus the association
      of timolol 0.5% and latanoprost 0.005% in glaucomatous patients.
AB  - BACKGROUND: New effective hypotensive agents have been recently introduced into
      clinical practice, but often more than one drug has to be used to prevent further
      visual field loss. The aim of this study was to evaluate the intraocular pressure
      (IOP)-lowering efficacy and safety of bimatoprost 0.03% compared with the
      association of timolol 0.5% and latanoprost 0.005% in open-angle glaucoma
      patients. METHODS: In this 6-month, prospective, parallel, randomised,
      investigator-masked clinical trial, 61 glaucomatous patients treated with timolol
      0.5% twice in both eyes were enrolled. The timolol 0.5% was replaced by
      bimatoprost 0.03% once daily (group I) or by latanoprost 0.005% plus timolol 0.5%
      (group II). IOP measurements were performed at the baseline visit and at days 15,
      30, 60, 90, 120 and 180. Digital colour photography was used to evaluate topical
      side effects. RESULTS: Fifty-six of the 61 patients were included for the intent
      to-treat analysis (28 in group I and 28 in group II). Baseline mean IOP was
      similar in the two groups (p=0.5). Both treatments lowered the mean IOP at every
      visit significantly compared with the baseline (p<0.01). Comparing the IOP
      reductions obtained by the two treatments, no significant differences were found
      at any time during the study. Conjunctival hyperaemia, skin pigmentation and
      eyelash growth in group I and headache in group II were the most common side
      effects observed during the study. CONCLUSIONS: Bimatoprost and the association
      of latanoprost plus timolol were equally effective in lowering the IOP in
      glaucomatous patients previously treated with timolol. Latanoprost plus timolol
      showed a better ocular safety profile.

PMID- 15241614
TI  - A comparison of three histological grading systems in endometrial cancer.
AB  - METHODS: To compare the architectural, nuclear and International Federation of
      Gynecology and Obstetrics (FIGO) grading systems in endometrial cancer 70
      consecutive patients with endometrial cancer were retrospectively reevaluated
      with three grading systems. RESULTS: Twenty-eight (40%), 27 (38.6%) and 14 (20%)
      cases were reported to have different grades when architectural vs nuclear,
      architectural vs. FIGO and nuclear vs. FIGO grading systems were compared in
      evaluation, respectively. Only 3 (42.8%) of the seven died patients had grade 3
      in all three grading systems. Five-year survival rates were 95.7, 80, and 78.6%
      for architectural grade 1, 2 and 3, respectively. Same rates were 96.7, 90.5, and
      78.9% for nuclear and 96, 91.7 and 81% for FIGO grading systems, respectively.
      CONCLUSIONS: Grades of the tumors often change when different grading systems are
      used. Postoperative treatment should be considered when at least one of the
      grading systems indicates poor differentiation.

PMID- 15241613
TI  - Influence of dimethylfumarate on experimental HSV-1 necrotizing keratitis.
AB  - BACKGROUND: This study was performed to investigate the influence of fumaric acid
      esters on the course of herpes stromal keratitis (HSK). METHODS: The corneas of
      BALB/c mice were inoculated with 105 plaque-forming units of herpes simplex virus
      1 (HSV-1, KOS strain). Groups of mice were treated intraperitoneally with
      phosphate buffered saline (PBS) (control mice), or with dimethylfumarate (DMF) at
      15 mg/kg of body weight dissolved in PBS daily for 28 days pre-infection and for
      14 days post-infection. The course of HSV-1 keratitis was studied clinically.
      Corneal sections were examined for inflammatory cell infiltration. The numbers of
      CD3, GR-1, CD11b and F4/80-expressing cells infiltrating the corneas were
      analyzed by immunohistochemistry. RESULTS: On day 14 after HSV infection, 72% of
      the mice in the control group had severe HSK. The development of HSK was reduced
      by DMF treatment in the DMF group (22%) (P=0.004). The total number of
      inflammatory cells and infiltration of polymorphonuclear-neutrophils (PMNs) were
      reduced in the corneas of DMF-treated mice. Compared to the PBS-treated mice,
      numbers of CD3, CD11b, GR-1 and F4/80-positive cells were reduced in the DMF
      group of mice. CONCLUSIONS: The course of experimental herpes stromal keratitis
      can be improved with systemic fumaric acid ester treatment. The improvement of
      keratitis correlates with a reduced corneal infiltration of T cells and
      mononuclear cells.

PMID- 15241615
TI  - Development of a new method in promoting fracture healing: multiple cryopreserved
      bone marrow injections using a rabbit model.
AB  - INTRODUCTION: It was hypothesized that multiple injections of cryopreserved bone
      marrow (BM) would promote fracture healing. MATERIALS AND METHODS: Experiments
      were performed to select a method for freezing BM nucleated cells based on the
      recovery rate, and to investigate the effects of frozen BM nucleated cells on
      fracture healing in a rabbit fracture nonunion model. Radiographic and
      histological evidences of bone union and new bone growth were compared between
      the experimental group and the control. RESULTS: Storage of BM nucleated cells in
      10% DMSO plus 90% autologous serum showed the optimal rate of cell recovery, cell
      viability, and osteoprogenitor cell recovery. Consecutive injections directly to
      the bone defect site with cryopreserved BM nucleated cells significantly
      increased the incidence of union, the radiographic volume and bone mineral
      density of repaired bone as compared with the control (p<0.05). CONCLUSION: A new
      method was developed to efficiently freeze BM nucleated cells, and cells
      cryopreserved with this method were found to promote fracture healing by multiple
      injections. It is suggested that cryopreserved BM injection provides an
      alternative approach for grafting in delayed union or nonunion.

PMID- 15241616
TI  - Long-term fate of uncemented, threaded acetabular components with smooth surface
      treatment: minimum 10-year follow-up of two different designs.
AB  - INTRODUCTION: In the 1970s and 1980s, uncemented, threaded acetabular components
      with smooth surface treatment were widely used in continental Europe for
      arthroplasty of the hip to overcome the high rate of aseptic loosening in
      cemented hip arthroplasty in young patients. There were several reports on short-
      and intermediate-term results, but information on survival in the longer term is
      not available at present. MATERIALS AND METHODS: In a consecutive series of 320
      patients, 348 threaded cups with smooth surface treatment (221 Mecring and 127
      Weill) had been implanted in combination with one type of uncemented stem.
      Patients were followed clinically and radiographically. The mean time of follow
      up was 12.4 (range 10-15) years (Mecring 11.9 years, Weill 13.3 years). RESULTS:
      In 76 hips the acetabular component had been revised (Mecring 56, Weill 20): 7
      hips for infection and 69 for aseptic loosening. Of the remainder, the cup had
      migrated in 55 hips, and 32 hips were awaiting revision. Survival at 14 years was
      63.8% (95%CI: 52.5-75.0%) for the Mecring and 76.2% (95%CI: 65.6-86.7%) for the
      Weill component. Radiolucent lines were present in 59 hips (31.9%). The median
      Harris Hip Score at follow-up was 84 points (Mecring 85, Weill 82). Radiographic
      loosening did not correlate with clinical outcome. CONCLUSION: These results
      support the view that smooth, threaded acetabular components do not provide
      satisfactory long-term fixation and should be abandoned.

PMID- 15241617
TI  - Arthroscopic reduction and suture fixation of displaced tibial intercondylar
      eminence fractures in adults.
AB  - INTRODUCTION: Tibial intercondylar eminence fractures are uncommon. In a review
      of the literature, most authors agreed that conservative treatment was suggested
      for non-displaced fractures. Displaced fractures were considered an indication
      for surgery. MATERIALS AND METHODS: Between April 2000 and November 2001, five
      adult displaced tibial eminence fractures were treated by arthroscopic reduction
      and non-absorbable suture fixation. Postoperatively, the knee was immobilized in
      a hinged knee brace locked in full extension with non-weight bearing for 4 weeks.
      Range of motion and quadriceps-strengthening exercises were started 4 weeks
      later. Partial weight-bearing was allowed in the following 4 weeks. RESULTS: The
      average follow-up was 24.6 months (range 18-36 months). Subjectively, there was
      no instability or residual pain in the knee. The patients were able to resume
      their normal activities. Objectively, the average Lysholm Score was 95.6 (range
      93-98). The average knee range of motion was 2 degrees to 135 degrees (range 0
      degree-140 degrees). All patients had a negative Lachman's test and no pivot
      shift phenomenon. All fractures showed good union according to radiological
      evaluation. CONCLUSION: Arthroscopy-assisted screw fixation is more stable, and
      it allows early exercise. However, the fragment must be large enough to be fixed
      with a screw. Comminuted or small fragments present limitations for screw
      fixation techniques. We used the non-absorbable intraligmentous suture to pull
      down the fragment regardless of small size or comminuted status. The technique is
      simple and provided secure fixation without damage to the ACL insertion. A second
      operation is not required to remove the hardware.

PMID- 15241618
TI  - Sigmoid colon volvulus in children: review of 19 cases.
AB  - The records of 19 patients with sigmoid colon volvulus (SCV) who were treated
      surgically in a 36.5-year-period were reviewed. Seven of them (37 %) had
      ileosigmoidal knotting (ISK). The age range was between 10 weeks and 17 years
      (mean 10 years), and 17 patients (90%) were male. In two cases (11%) there was
      previous SCV history. The mean symptom duration was 57 h (range 24-96), and three
      patients (16%) were in shock. The main symptoms were abdominal pain (90%),
      distention (79%), vomiting (74%), and obstipation (58%), and the main signs were
      abdominal tenderness (90%), distention (79%), absence of stool in the rectum and
      hypo- or akinetic bowel sounds (58%), muscular rigidity (53%), hyperkinetic bowel
      sounds (32%), and melanotic stool in the rectum (21%). The torsion was found in a
      clockwise direction in 47%, and the torsion degree was 360 in 42%. In four
      patients (21%) there was no gangrene (one with ISK), whereas in 15 (79%) sigmoid
      colon was gangrenous (six with ISK, in whom small bowel was also gangrenous). In
      nongangrenous cases, detorsion (11%) or sigmoidopexy (11%) was performed. In
      gangrenous cases, gangrenous sigmoid colon was resected, and Hartmann's procedure
      (74%) or primary anastomosis (5%) was performed. In those with associated
      gangrene of the small bowel, resection and enteroenteric anastomosis were done.
      Four patients (21%) died, with the most common cause of death being toxic shock.
      In 11 patients, including five with SCV and six with ISK, no recurrence was seen
      in a mean 18-year follow-up period (range 8-39). As a result, preoperative
      resuscitation, prompt surgery, and postoperative support are important in
      emergent SCV in children.

PMID- 15241619
TI  - Ranitidine-enhanced 99mtechnetium pertechnetate imaging in children improves the
      sensitivity of identifying heterotopic gastric mucosa in Meckel's diverticulum.
AB  - Meckel's diverticulum is the most common congenital gastrointestinal anomaly.
      (99m )Technetium pertechnetate imaging (Meckel's scan) is the best noninvasive
      method used to diagnose this condition when heterotopic gastric mucosa (HGM) is
      present. Although cimetidine enhancement has been shown to improve sensitivity of
      the Meckel's scan, ranitidine enhancement has also been advocated; however, this
      recommendation is based on unpublished data. Thirty-seven children with confirmed
      Meckel's diverticulum were reviewed retrospectively. Of eight children with HGM
      in the Meckel's diverticulum who presented with profuse rectal bleeding and
      underwent the conventional Meckel's scan, three of them (37.5%) had a false
      negative study. Ranitidine, when administered either intravenously or orally for
      24 h prior to the Meckel's scan, enhanced the sensitivity of this test to 87.5%
      in our patient cohort.

PMID- 15241622
TI  - Diagnostic performance of CT versus MR in detecting aldosterone-producing adenoma
      in primary hyperaldosteronism (Conn's syndrome).
AB  - The aim of the present study is to compare the diagnostic performance of CT and
      MR imaging in detecting aldosterone-producing adenoma and to compare the
      interobserver variability in the detection of an aldosterone-producing adenoma on
      CT and MR. A retrospective study of 34 patients with primary hyperaldosteronism
      was performed. A total of 17 cases of aldosterone-producing adenoma and 17 cases
      of bilateral adrenal hyperplasia were included. The final diagnosis of an adenoma
      was made by surgery with histological confirmation, whereas that of bilateral
      adrenal hyperplasia was made on adrenal venous sampling or a good biochemical and
      clinical response following medical treatment alone and in the absence of a
      unilateral radiological abnormality. The CT (n=30) and MR (n=24) scans were
      reviewed independently by two radiologists experienced in adrenal imaging, who
      were unaware of the cause of the primary hyperaldosteronism. The diagnostic
      performances of both observers in detecting an aldosterone-producing adenoma on
      CT and MR imaging were compared. The 16 adenomatous nodules that were detected on
      imaging ranged from 1 to 4.75 cm in diameter. The calculated sensitivity and
      specificity for detecting aldosterone-producing adenoma were 87 and 93% for one
      observer and 85 and 82% for the other observer on CT, and 83 and 83% for one
      observer and 92 and 92% for the other observer on MR, respectively. Receptor
      operating characteristics curve analysis showed similar performances of both
      observers in detecting an aldosterone-producing adenoma on CT and MR imaging.
      There was good interobserver agreement on CT (k=0.71) and on MR (k=0.67). We have
      demonstrated comparable diagnostic performance and good interobserver agreement
      on CT and MR imaging for the detection of aldosterone-producing adenoma.

PMID- 15241624
TI  - [Classification of pulmonary alveolar proteinosis in newborns, infants, and
      children].
AB  - Pulmonary alveolar proteinoses are rare pulmonary diseases characterised by an
      intraalveolar accumulation of surfactant protein A. Subtyping of alveolar
      proteinoses: Type I alveolar proteinoses: severe respiratory insufficiency in
      newborns, which will take a lethal course without lung transplant; hereditary SP
      B deficiency and an intraalveolar accumulation of N-terminal incompletely
      processed SP-C. Type II alveolar proteinoses: occur in newborns and infants;
      often take a lethal course; show intraalveolar accumulation of precursors of SP-B
      and mature SP-B as well as an accompanying interstitial lung disease of variable
      severity. Type III alveolar proteinoses: in infants and children; do not
      generally take a lethal course; they are characterised by an intraalveolar
      accumulation of precursors of SP-B and mature SP-B without accompanying
      interstitial lung disease. "Cryptogenic" congenital, acquired (idiopathic), and
      secondary type III alveolar proteinoses can be distinguished. In newborns,
      infants, and children with pulmonary alveolar proteinosis, a detailed
      pathological-anatomical examination including immunohistochemical and molecular
      genetic analyses, should be performed in order to optimise the therapeutical
      management.

PMID- 15241623
TI  - The Iml3 protein of the budding yeast is required for the prevention of
      precocious sister chromatid separation in meiosis I and for sister chromatid
      disjunction in meiosis II.
AB  - The mitotic kinetochore of the budding yeast contains a number of proteins which
      are required for chromosome transmission but are non-essential for vegetative
      growth. We show that one such protein, Iml3, is essential for meiosis, in that
      the absence of this protein results in reduced spore viability, precocious sister
      chromatid segregation of artificial and natural chromosomes in meiosis I and
      chromosome non-disjunction in meiosis II.

PMID- 15241625
TI  - The influence of personality traits on the subjective outcome of operative hallux
      valgus correction.
AB  - We studied prospectively the influence of personality traits on the subjective
      outcome of a chevron osteotomy in 42 patients with hallux valgus. The mean age of
      patients was 48.3 (20-70) years. Personality traits were evaluated by the means
      of the Freiburg Personality Inventory (FPI-R). Three months postoperatively 37
      patients were satisfied, and five patients not satisfied with the operative
      procedure. The preoperative AOFAS Score improved from an average of 48.7 (30-65)
      points to 87.9 (50-100) points. A comparison of satisfied and dissatisfied
      patients revealed statistically significant differences in the personality traits
      aggressiveness (p=0.003), extraversion (p=0.001) and health worries (p=0.04). The
      postoperative hallux valgus angle was 12.2+/-7.8 degrees and 13.4+/-8.3 degrees
      (p=0.74) among satisfied and not satisfied patients, respectively, and the
      intermetatarsal angle (I-II) was 7.4+/-2.5 degrees and 7.6+/-4 degrees (p=0.89),
      respectively. The results suggest that the patient's subjective result after the
      operative correction may be influenced by some individual, personality profiles.

PMID- 15241626
TI  - Results of surgical versus non-surgical treatment of Achilles tendon rupture.
AB  - Between 1990 and 2001, 292 patients with acute Achilles tendon rupture were
      admitted to our institution. Depending on the day of admission patients were
      allocated either to the Department of Trauma Surgery or to the Department of
      Orthopaedics. Two hundred and twelve patients (mean age 37+/-9.4 years) were
      treated with surgical suture followed by plaster for 6 weeks. Eighty patients
      were treated non-surgically with splinting for 12 weeks. For both groups mean
      follow-up was 6+/-3 years. There were 14 re-ruptures, ten after surgical repair
      and four after non-surgical treatment. In the surgical group there were seven
      major wound problems, 11 minor wound complications and six patients with
      complaints from the sural nerve. In the non-surgical group one patient suffered a
      pulmonary embolism after a re-rupture, 3 months after the initial rupture. There
      was no difference in mean ankle score and patient-satisfaction score between
      groups. Only 52% regained their original sports activity level, slightly better
      in the surgically treated group. With a non-significant difference in re-rupture
      rate but relatively more complications after surgical repair, non-surgical
      treatment is preferred. With a slightly better recovery of sports activity after
      surgical repair, this might be used as an argument for surgical treatment in
      young athletes.

PMID- 15241627
TI  - Clinical feasibility of two-step streptavidin/111In-biotin scintigraphy in
      patients with suspected vertebral osteomyelitis.
AB  - PURPOSE: Streptavidin accumulates at sites of inflammation and infection as a
      result of increased capillary permeability. In addition to being utilised by
      bacteria for their own growth, biotin forms a stable, high-affinity non-covalent
      complex with avidin. The objective of this investigation was to determine the
      diagnostic performance of two-step streptavidin/111In-biotin imaging for
      evaluating patients with suspected vertebral osteomyelitis. METHODS: We evaluated
      55 consecutive patients with suspected vertebral osteomyelitis (34 women and 21
      men aged 27-86 years), within 2 weeks after the onset of clinical symptoms.
      Thirty-two of the patients underwent magnetic resonance imaging (MRI) and 24,
      computed tomography (CT). DTPA-conjugated biotin was radiolabelled by incubating
      500 microg of DTPA-biotin with 111 MBq of 111In-chloride. Two-step scintigraphy
      was performed by first infusing 3 mg streptavidin intravenously, followed 4 h
      later by 111In-biotin. Imaging was begun 60 min later. RESULTS:
      Streptavidin/111In-biotin scintigraphy was positive in 32/34 patients with spinal
      infection (94.12% sensitivity). The study was negative in 19/21 patients without
      infection (95.24% specificity). The corresponding results for MRI and CT were
      54.17% and 35.29% (sensitivity), and 75% and 57.14% (specificity), respectively.
      All statistical parameters of diagnostic performance (Youden's J index, kappa
      measure of agreement with correct classification, accuracy, sensitivity,
      specificity, positive likelihood and negative likelihood) were clearly better for
      streptavidin/111In-biotin scintigraphy than for either MRI or CT. CONCLUSION:
      Streptavidin/111In-biotin scintigraphy is highly sensitive and specific for
      detecting vertebral osteomyelitis in the first 2 weeks after the onset of
      clinical symptoms, and is potentially very useful for guiding clinical decisions
      on instituting appropriate therapy.

PMID- 15241628
TI  - Splenectomy? No, thank you!

PMID- 15241629
TI  - Waiting for Godot: waiting in nuclear medicine.

PMID- 15241630
TI  - Registration accuracy of 153Gd transmission images of the brain.
AB  - PURPOSE: The aim of the study was to determine the accuracy of non-rigid nine
      parameter image registrations based on 153Gd transmission computed tomography
      (TCT) images as compared with those based on 99mTc-ethyl cysteinate dimer (ECD)
      images and to assess whether normalised mutual information (NMI) or count
      difference (CD) should be used. METHODS: TCT and ECD data were acquired in 25
      randomly selected patients. Emission images were registered to an ECD template
      with a CD cost function. The same registration parameters were applied to the
      transmission images to create a TCT template. All TCT images were registered to
      the TCT template and the same registration parameters were applied to the ECD
      images. The procedure was repeated with NMI as cost function. Accuracy of both
      ECD-based and TCT-based registrations was assessed by comparing the normalisation
      parameter values and regional activities in the spatially normalised ECD images,
      using a mixed-model analysis of variance (ANOVA). Scheffe post hoc tests were
      performed. RESULTS: No significant differences were found between ECD/CD, ECD/NMI
      and TCT/CD, suggesting that ECD registration can be done with either CD or NMI,
      and that TCT registration using CD is equally as accurate as ECD registration.
      The accuracy of TCT registration with NMI was lower, with discrepancies occurring
      in the frontal inferior region and the cerebellum. The analysis of normalisation
      parameters indicated that z-scaling is underestimated and yz-rotation
      overestimated with TCT/NMI registration. CONCLUSION: We conclude that ECD
      registrations with CD or NMI are as accurate as TCT registrations with CD and
      that TCT registrations with NMI should be avoided.

PMID- 15241633
TI  - Mutation study of conserved amino acid residues of Spirulina delta 6-acyl-lipid
      desaturase showing involvement of histidine 313 in the regioselectivity of the
      enzyme.
AB  - In the cyanobacterium Spirulina platensis, the desaturation process is carried
      out by three desaturases: the Delta(9), Delta(12) and Delta(6) desaturases,
      encoded by desC, desA and desD, respectively. The Delta(6) desaturase is
      responsible for the catalysis of linoleic acid, yielding gamma-linolenic acid
      (18:3(Delta 9,12,6)), the end-product of the process. In this study, the desD
      gene was expressed in Escherichia coli using a pTrcHisA expression system. In
      order to identify the amino acid residues involved in the enzymatic activity, a
      sequence comparison was performed using various organisms. The alignment revealed
      three conserved histidine clusters, a number of conserved residues among all
      listed organisms and a few conserved residues among cyanobacterial species
      possibly involved in the desaturation activity. A series of site-directed
      mutations were generated in the desD gene to evaluate the role of these residues
      vis-a-vis the enzyme function. This approach revealed that: (1) H313 is involved
      in the regioselectivity of the enzyme, (2) the three histidine clusters together
      with H313, H315, D138 and E140 are required for enzymatic activity, most likely
      as providers of the catalytic Fe center and (3) W294 is also essential for the
      activity of Delta(6) desaturase, possibly by forming part of the substrate
      binding pocket.

PMID- 15241634
TI  - Identification of four allelic variants of the dog IGHA gene.
AB  - Multiple IgA subclasses have been identified in humans, primates and lagomorphs,
      whereas in mice, cattle and dogs only a single subclass has been identified. The
      two human subclasses (IgA1 and IgA2) are defined by a difference in the length of
      the hinge region of the alpha chains between the CH1 and CH2 domains. The single
      IgA subclass so far identified in dogs has an alpha-chain hinge region with a
      predicted amino-acid sequence similar to that of the human alpha1 chain. Allelic
      variants that differ in the coding sequence of the hinge region have been
      identified in mice and pigs. In order to investigate whether allelic variants are
      present in dogs, a portion of the IGHA gene from eight individual dogs was cloned
      and sequenced. Four sequence variants were identified, and these differed in the
      coding region of their hinge. A major difference between the variants was the
      presence of a base polymorphism in the splice acceptor site for the second exon,
      which resulted in shortening of the hinge in two of the variants. Individuals
      expressed one or two of the variants identified, suggesting they may be
      heterozygous or homozygous. Further work is required to determine the effect of
      the variation on the biological activity of dog IgA and any relationship to
      susceptibility to mucosal disease.

PMID- 15241635
TI  - When does play panting occur during social play in wild chimpanzees?
AB  - To clarify the social functions of play panting in chimpanzees, I investigated
      when they emitted play panting in social play and how the interactions were
      affected by the occurrence of play panting. The subjects were the M-group
      chimpanzees living in Mahale, Tanzania. The following observations were made: (1)
      chimpanzees emitted play panting when they were tickled or chased but rarely did
      so when they tickled or chased others. Chimpanzee play panting does not have the
      function of a play signal communicating that these "aggressive" actions are
      performed not as aggression but as play. (2) Chimpanzees emitted play panting
      more often when they received "aggressive" actions that supposedly elicited
      higher arousal. (3) A chimpanzee tended to continue to perform "aggressive"
      actions when the target emitted play panting. Play panting activates the
      interaction of social play by encouraging the performer to continue tickling or
      chasing. These results can be summarized as showing that chimpanzee play panting
      serves as positive feedback to the play partner for continuing somewhat fragile
      interactions, which may contain the risk of excessive arousal and the risk of
      confusing "defensive" actions by the target of the "aggressive" actions with real
      efforts to escape the situation.

PMID- 15241636
TI  - Form and function of the oblique cord (chorda obliqua) in anthropoid primates.
AB  - The oblique cord of the forearm in humans is a ligament connecting the
      anterolateral aspect of the ulna proximally to the posteromedial aspect of the
      radius distally, inserting just below the radial tuberosity. Its functional
      significance is uncertain, but it has been proposed that the ligament limits
      supination of the forearm or aids in resisting buckling failure in the curved
      radius. These functional explanations are unsatisfactory for bipedal humans who
      do not use their forelimbs in weight support. Furthermore, there are no
      evolutionary explanations for its presence in humans. The purpose of this study
      was to investigate the distribution and form of the oblique cord in non-human
      primates and to explore its possible functional significance and evolutionary
      origin in humans. Soft tissue dissections of anthropoid primates revealed the
      presence of an oblique cord in New and Old World monkeys and Asian apes. It was
      absent in all atelines. Passive manipulation of the two forearm bones in all
      specimens revealed that the ligament becomes most taut in pronation contrary to
      the proposed human condition. Isolated radii show that the oblique cord's radial
      insertion lacks a clear relationship with bone curvature, thus providing little
      support for the hypothesis of preventing buckling failure. The oblique cord's
      involvement in reducing bending strain in the curved radius is also unlikely. It
      is suggested here that the ligament may have a role in maintaining elbow
      stability in quadrupedal primates. Therefore, the function of the oblique cord in
      anthropoid primates suggests that its presence in modern humans may be a
      morphological and functional remnant from a quadrupedal ancestry.

PMID- 15241631
TI  - Fluorinated tracers for imaging cancer with positron emission tomography.
AB  - 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer
      used in routine clinical positron emission tomography (PET). Fluorine-18 is
      considered the ideal radioisotope for PET imaging owing to the low positron
      energy (0.64 MeV), which not only limits the dose rate to the patient but also
      results in a relatively short range of emission in tissue, thereby providing high
      resolution images. Further, the 110-min physical half-life allows for high-yield
      radiosynthesis, transport from the production site to the imaging site and
      imaging protocols that may span hours, which permits dynamic studies and
      assessment of potentially fairly slow metabolic processes. The synthesis of
      fluorinated tracers as an alternative to FDG was initially tested using
      nucleophilic fluorination of the molecule, as performed when radiolabelling with
      iodine-124 or bromide-76. However, in addition to being long, with multiple
      steps, this procedure is not recommended for bioactive molecules containing
      reactive groups such as amine or thiol groups. Radiochemical yields are also
      often low. More recently, radiosynthesis from prosthetic group precursors, which
      allows easier radiolabelling of biomolecules, has led to the development of
      numerous fluorinated tracers. Given the wide availability of 18F, such tracers
      may well develop into important routine tracers. This article is a review of the
      literature concerning fluorinated radiotracers recently developed and under
      investigation for possible PET imaging in cancer patients. Two groups can be
      distinguished. The first includes "generalist" tracers, i.e. tracers amenable to
      use in a wide variety of tumours and indications, very similar in this respect to
      FDG. These are tracers for non-specific cell metabolism, such as protein
      synthesis, amino acid transport, nucleic acid synthesis or membrane component
      synthesis. The second group consists of "specific" tracers for receptor
      expression (i.e. oestrogens or somatostatin), cell hypoxia or bone metabolism.

PMID- 15241637
TI  - First experimental evidence for female mate choice in a nocturnal primate.
AB  - Female mate choice can be hypothesised in most nocturnal primates, since females
      show a higher investment in their offspring than males. The aim of this
      experimental study was to investigate if female grey mouse lemurs perform mate
      choice and whether age, relatedness (to the male), or male advertisement call
      activity systematically influence their decisions. A two-way mate choice design
      was developed in which females could choose between two males. Mate choice was
      deduced from the time spent in proximity to the males and from mating behaviour.
      During oestrus 12 of 17 females participated actively in the experiment and all
      of them showed either a significant spatial (n = 11) or behavioural (n = 1)
      preference for one male. In four cases copulations were observed. The influence
      of age on female mate choice was not statistically significant. In the cases with
      copulations, however, females mostly preferred the older male. This might
      indicate a preference for older age as an indicator of experience, fitness,
      and/or status. The influence of relatedness on female mate choice could not be
      definitely clarified. However, results imply a mechanism of kin recognition on
      the basis of familiarity. In the majority of choices, females preferred the male
      with higher trill call activity. Since trill call activity correlates with the
      relative dominance status of males, these results suggest an importance of the
      male dominance status for female mate choice in grey mouse lemurs. Altogether our
      findings indicate that females use a complex of different cues to choose their
      mates.

PMID- 15241640
TI  - Masked hypertension: a clinical entity or statistical gymnastics?

PMID- 15241641
TI  - Endothelin receptor antagonists and cerebral vasospasm.

PMID- 15241642
TI  - Segmental orthostatic fluid shifts.

PMID- 15241643
TI  - Syncope and seizures-differential diagnosis and evaluation.
AB  - Syncope and seizures are common conditions and pose diagnostic challenges for the
      clinician. The cumulative lifetime incidence of epilepsy is 3%, and the incidence
      of a first attack of syncope is 6.2 per 1000 person-years in the general
      population. Although the underlying pathophysiological processes are distinct,
      seizures and syncope share some clinical characteristics which may lead to
      diagnostic confusion. Confounding matters further is the fact that seizures and
      syncope may coexist in a given patient. For example, some conditions such as
      prolonged QT syndrome may result in both arrhythmia-associated syncope and
      seizures, and in some cases, seizures may result in cardiac arrhythmia and
      syncope. The clinical history, examination, electrocardiography, and combined
      EEG/ECG telemetry are all helpful in the diagnosis of seizures and syncope.

PMID- 15241644
TI  - Is there any real target organ damage associated with white-coat normotension?
AB  - Subjects with white-coat normotension (WCNT) or masked hypertension, i. e. a
      normal office blood pressure (BP) reading but elevated ambulatory blood pressure
      monitoring (ABPM) results, have not been extensively studied. The aim of this
      work was to compare true normotensive subjects (NT), WCNT and nevertreated
      hypertensive subjects (HT, with elevated BP according to both office and ABPM
      readings). One hundred and fifty subjects were recruited to analyze
      cardiovascular characteristics. Office BP readings coupled with ABPM results were
      used to break this population down into 51 NT, 18 WCNT and 81 HT. Office BP
      readings were higher in WCNT than in NT. In WCNT, carotid-femoral pulse wave
      velocity (PWV) was higher than in NT (with a borderline significance p = 0.05)
      and the standing baroreflex sensitivity (BRS) was lower (p = 0.04). Left
      ventricular mass index (LVMI) and carotid intima-media thickness (IMT) tended to
      increase and BRS measurements tended to decrease from NT through WCNT to HT.
      However, the difference across the board is only significant (p < 0.05) between
      NT and HT. If only the subset of NT subjects with SBP readings comparable to
      those of the WCNT subjects (i. e. SBP > 120 mmHg) is considered, no significant
      difference is detected in PWV and the only difference is detected in BRS
      (respectively for standing [PS+/RR+]: 5.7 +/- 1.4 ms/mmHg vs 4.9 +/- 1.2 ms/mmHg,
      p = 0.04). In conclusion, the principal cardiovascular differences measured
      between the NT and the WCNT can probably be explained by their difference in
      clinical level of pressure at rest. Only the BRS remains different between NT and
      WCNT when the real level of clinical pressure is taken into account.

PMID- 15241645
TI  - Use of lower abdominal compression to combat orthostatic hypotension in patients
      with autonomic dysfunction.
AB  - The aim of this study was to investigate in patients with neurogenic orthostatic
      hypotension the mechanism and usefulness of abdominal compression to increase
      standing blood pressure. In three protocols, 23 patients underwent abdominal
      compression. Protocol 1 evaluated in a 40-60 degrees head-up-tilt position, the
      effect of abdominal compression on caval vein and femoral diameter, arterial
      blood pressure and hemodynamics. Protocol 2 documented the relationship between
      the level of compression and the arterial pressure response. Protocol 3
      investigated the ability to maintain standing blood pressure by an elastic
      binder. During head-up-tilt, compression (40 mm Hg) resulted in a reduction in
      diameter of the caval vein (mean -2.6mm, range -1.4 to 0.6), without a change in
      femoral vein diameter. Stroke volume increased by 14 % (range -1 to 23) and blood
      pressure (systolic/diastolic) by 30/14 mmHg (range 7/2 to 69/36), both p < 0.05;
      40 mmHg compression was associated with a higher pressure response than 20 mmHg
      (mean 18/8 mmHg, range 6/2 to 43/20 vs. mean 9/4 mmHg, range -1/0 to 18/8, p <
      0.05). Elastic abdominal binding increased standing blood pressure with 15/6 mmHg
      (range -3/3 to 36/14, p < 0.05). We conclude that in patients with neurogenic
      orthostatic hypotension, abdominal compression increases standing blood pressure
      to a varying degree by increasing stroke volume.

PMID- 15241646
TI  - Stroke volume monitored by modeling flow from finger arterial pressure waves
      mirrors blood volume withdrawn by phlebotomy.
AB  - Rate-controlled blood withdrawal was used to reduce cardiac preload and
      consequently stroke volume in patients with normal cardiac function. Twelve
      patients with asymptomatic hereditary hemochromatosis, undergoing regular
      phlebotomy therapy, volunteered for the study. An average volume of 375 ml was
      withdrawn in an average period of 6.4 min. Finger pressure was continuously
      measured by a Finometer device which includes the Beatscope software for deriving
      the stroke volume from the blood pressure waveform. Blood withdrawal resulted in
      reduction of the stroke volume estimates (from 94.0 +/- 5.2 to 80.7 +/- 5.3, P <
      0.05) together with a reduced pulse pressure (from 53.0 +/- 3.5 to 47.1 +/- 3.2,
      P < 0.05). No significant changes in heart rate (75.2 +/- 3.7 versus 78.3 +/- 4.5
      beats/min) were observed. Calculated cardiac output was reduced while calculated
      total peripheral resistance was elevated after blood withdrawal. Beat-to-beat
      analysis demonstrated a significant linear regression between most of the
      hemodynamic indices and the volume withdrawn. The highest correlation
      coefficients were found for the stroke volume (0.88 +/- 0.01, P < 0.001) and the
      pulse pressure (0.80 +/- 0.04, P < 0.001) corresponding also to the highest
      slopes for the lines relating these measures to the relative blood volume
      withdrawn. The non-invasive estimation of finger blood pressure can be used to
      derive simple on-line indices (pulse pressure, stroke volume using the Modelflow)
      of cardiac preload, which are of major interest in the monitoring of
      cardiovascular status.

PMID- 15241647
TI  - Inhibitory effect of electroacupuncture (EA) on the pressor response induced by
      exercise stress.
AB  - We examined the effect of EA on the exercise stress-induced pressor response in
      healthy adult subjects of both sexes. Each subject was subjected to a bicycle
      exercise test using a ramp protocol once/week for three or four weeks. Subjects
      were asked to perform the following tests in random order: 1) a baseline exercise
      test without EA and 2) exercise after acupuncture at P 5-6, LI 4-L 7 and/or G 37
      39 acupoints. Brachial systolic (SBP), diastolic (DBP), and mean blood pressures
      (MBP), heart rate (HR) and the rate-pressure product (RPP, systolic BP x HR/100)
      were measured every three min, while a 12 lead ECG was monitored continuously. We
      observed increases in MBP, SBP, HR and RPP in all 17 subjects during exercise. In
      12 of the 17 subjects (71 %), EA for 30 min before exercise, either at Jianshi
      Neiguan acupoints (P 5-6) or Hegu-Lique acupoints (LI 4-L 7), led to an increase
      in maximal workload, and reduced peak SBP, MBP and RPP responses to exercise; EA
      did not alter DBP or HR responses in these subjects. EA at control acupoints
      (Guangming-Xuanzhong acupoints, G 37-39) in five subjects did not alter the
      hemodynamic responses. Seven additional subjects were enrolled to study the
      effect of EA during a bicycle exercise test using a constant workload. The
      results were similar, in five of the seven subjects SBP, MBP and RPP after
      exercise were attenuated significantly by EA at P 5-6. We conclude that EA at
      specific acupoints improves exercise capacity and reduces the hemodynamic
      responses in approximately 70% of normal subjects.

PMID- 15241648
TI  - Spontaneous baroreflex measurement in the assessment of cardiac vagal control.
AB  - Spontaneous baroreflex sensitivity (SBR) has been suggested to be a measure of
      tonic parasympathetic cardiac control. The decrease of SBR during vagal
      inhibition was proven before. In this study, we investigated the response of SBR
      during vagal activation by administering intravenous atropine and phenylephrine
      in eight and ten healthy volunteers respectively. Atropine was given at a rate of
      0.5 micro g/kg/min for 20 minutes and the infusion rate of phenylephrine was
      adjusted to increase the blood pressure 20 to 30 mmHg above baseline value. We
      found that SBR at first increased from 16.9 +/- 9.5 to 41.5 +/- 24.9 ms/mm Hg (p
      < 0.05) and then decreased to 8.9 +/- 6.2 ms/mm Hg (p < 0.05 compared with the
      peak value) after the initiation of atropine infusion. SBR also increased
      significantly (27.2 +/- 12.5 to 49.6 +/- 11.3 ms/mm Hg, p < 0.01) during
      phenylephrine infusion. The authors propose SBR as a measure of cardiac vagal
      effect because SBR increases under vagal activation.

PMID- 15241649
TI  - Reproducibility of heart rate and blood pressure variability in patients with
      chronic obstructive pulmonary disease.
AB  - Wide variations in respiratory rate and hypoxic stimulation of chemoreceptors may
      produce unreliable autonomic results in patients with COPD. We studied the
      reproducibility of two consecutive measurements of heart rate variability (HRV)
      and blood pressure variability (BPV) by time frequency analysis in patients with
      COPD while controlling respiratory rate and oxygen hemoglobin saturation
      (SaO(2)). Reproducibility was assessed by paired t-tests and correlation analyses
      between repeated measures. Correlation analyses of the log transformed low (LF)
      and high frequency (HF) HRV were x 11.5 +/- 1.1 in measurement A and x 11.5 +/-
      1.0 in measurement B (r = 0.89, p < 0.0001), and x 10.5 +/- 1.1 in measurement A
      and x 10.6 +/- 1.1 in measurement B (r = 0.89, p < 0.0001) respectively. The log
      transformed LF and HF BPV were x 4.9 +/- 1.3 in measurement A and x 5.3 +/- 0.9
      in measurement B (r = 0.70, p < 0.0002), and x 6.4 +/- 1.3 in measurement A and
      6.6 +/- 1.2 in measurement B (R = 0.71 p < 0.0001) respectively. In conclusion,
      time frequency analysis of HRV and BPV is reproducible and reliable in patients
      with COPD while controlling their respiratory rate and oxygen hemoglobin
      saturation. Reproducibility of these measurements may allow for a non-invasive
      evaluation of autonomic tone in response to treatments in COPD patients.

PMID- 15241650
TI  - The effects of endothelin antagonist BQ-610 on cerebral vascular wall following
      experimental subarachnoid hemorrhage and cerebral vasospasm.
AB  - Endothelin, a potent vasoconstrictor, has been found to increase in the
      cerebrospinal fluid and serum of patients following subarachnoid hemorrhage (SAH)
      and to play a major role in the development of cerebral vasospasm. The aim of
      this study is to investigate the role of endothelin-A antagonist BQ-610 in the
      experimentally performed cerebral vasospasm following SAH. Thirty New Zealand
      rabbits were divided into three groups (each n = 10): group A, control group;
      Group B, SAH group; Group C, treatment (endothelin antagonist BQ-610 treated)
      group. In the study, the rabbits developed vasospasm after injection of
      intracisternal autolog blood into the cisterna magna. After cerebral vasospasm
      development, in group C, endothelin antagonist BQ-610 was injected
      intracisternally. Morphometrically, basilar artery lumen was constricted 25% and
      62% compared to the control group (group A) in the endothelin treated group
      (group C) and the endothelin untreated group (group B), respectively.
      Histopathological findings of the basilar artery wall confirmed the therapeutic
      effect of endothelin antagonist in vasospasm development. Endothelin-A receptor
      antagonist BQ-610 has a therapeutic effect in the cerebral vasospasm following
      experimentally performed subarachnoid hemorrhage when used intracisternally.

PMID- 15241651
TI  - Intestinal obstruction associated with oral midodrine.
AB  - We report a case of severe ileus possibly related to midodrine. To our knowledge,
      this case report is the first one suggesting an inhibitory effect of midodrine on
      intestinal motility. The potential pharmacological mechanisms leading to this
      adverse drug reaction are discussed below.

PMID- 15241654
TI  - Hemispheric differences in the recognition of partly occluded objects by newly
      hatched domestic chicks (Gallus gallus).
AB  - Domestic chicks are capable of perceiving as a whole objects partly concealed by
      occluders ("amodal completion"). In previous studies chicks were imprinted on a
      certain configuration and at test they were required to choose between two
      alternative versions of it. Using the same paradigm we now investigated the
      presence of hemispheric differences in amodal completion by testing newborn
      chicks with one eye temporarily patched. Separate groups of newly hatched chicks
      were imprinted binocularly: (1) on a square partly occluded by a superimposed
      bar, (2) on a whole or (3) on an amputated version of the square. At test, in
      monocular conditions, each chick was presented with a free choice between a
      complete and an amputated square. In the crucial condition 1, chicks tested with
      only their left eye in use chose the complete square (like binocular chicks would
      do); right-eyed chicks, in contrast, tended to choose the amputated square.
      Similar results were obtained in another group of chicks imprinted binocularly
      onto a cross (either occluded or amputated in its central part) and required to
      choose between a complete or an amputated cross. Left-eyed and binocular chicks
      chose the complete cross, whereas right-eyed chicks did not choose the amputated
      cross significantly more often. These findings suggest that neural structures fed
      by the left eye (mainly located in the right hemisphere) are, in the chick, more
      inclined to a "global" analysis of visual scenes, whereas those fed by the right
      eye seem to be more inclined to a "featural" analysis of visual scenes.

PMID- 15241655
TI  - Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene
      (SPR) in a patient with dopa-responsive dystonia.
AB  - The search for mutations in genes coding for components of the biopterin pathway
      other than GTPCH1 revealed a mutation in the gene coding for sepiapterin
      reductase (SPR) in 1 of 95 patients with GCH1-negative dopa-responsive dystonia
      (DRD). The mutation detected in SPR is a G-->A transition at position -13 of the
      untranslated region of the gene. This resulted in drastically reduced activity of
      sepiapterin reductase in the patient's fibroblasts. The findings indicate that
      haploinsufficiency of SPR can be a rare cause of DRD.

PMID- 15241656
TI  - Transcript map of the candidate region for HSNI with cough and gastroesophageal
      reflux on chromosome 3p and exclusion of candidate genes.
AB  - Dominantly inherited sensory neuropathy (HSNI) is a degenerative disorder of
      sensory neurons characterized predominantly by sensory loss with mild motor
      impairment. Recently our group identified a locus on chromosome 3p for a new form
      of HSNI associated with cough and gastroesophageal reflux (GER). Haplotype
      analysis in a second family refined the interval to a 3.4-cM region that includes
      the candidate genes TOP2B and SLC4A7. The genes TOP2B and SLC4A7 and five other
      characterized genes that map within the critical interval have been investigated
      and excluded from having a pathogenic role in HSNI with cough and GER. Two novel
      single nucleotide polymorphisms were identified; however both changes were
      observed in affected and non-affected individuals, suggesting that they have no
      relation to the disease. We have used the resources of the Human Genome Project
      to report a transcript map of the region on chromosome 3p24 containing the HSNI
      with cough and GER locus.

PMID- 15241658
TI  - Psychrophilic Pseudomonas syringae requires trans-monounsaturated fatty acid for
      growth at higher temperature.
AB  - A psychrophilic bacterium, Pseudomonas syringae (Lz4W) from Antarctica, was used
      as a model system to establish a correlation, if any, between thermal adaptation,
      trans-fatty acid content and membrane fluidity. In addition, attempts were made
      to clone and sequence the cti gene of P. syringae (Lz4W) so as to establish its
      characteristics with respect to the cti of other Pseudomonas spp. and also to in
      vitro mutagenize the cti gene so as to generate a cti null mutant. The bacterium
      showed increased proportion of saturated and trans-monounsaturated fatty acids
      when grown at 28 degrees C compared to cells grown at 5 degrees C, and the
      membrane fluidity decreased with growth temperature. In the mutant, the trans
      fatty acid was not synthesized, and the membrane fluidity also decreased with
      growth temperature, but the decrease was not to the extent that was observed in
      the wild-type cells. Thus, it would appear that synthesis of trans-fatty acid and
      modulation of membrane fluidity to levels comparable to the wild-type cells is
      essential for growth at higher temperatures since the mutant exhibits growth
      arrest at 28 degrees C. In fact, the cti null mutant-complemented strain of P.
      syringae (Lz4W-C30b) that was capable of synthesizing the trans-fatty acid was
      indeed capable of growth at 28 degrees C, thus confirming the above contention.
      The cti gene of P. syringae (Lz4W) that was cloned and sequenced exhibited high
      sequence identity with the cti of other Pseudomonas spp. and exhibited all the
      conserved features.

PMID- 15241657
TI  - Differential pressure resistance in the activity of RNA polymerase isolated from
      Shewanella violacea and Escherichia coli.
AB  - RNA polymerase was purified from the piezophile Shewanella violacea DSS12, and
      the transcriptional activity after pressure treatment was compared with that of
      the mesophile Escherichia coli. Application of pressure at 100 MPa for 30 min
      reduced the E. coli RNA polymerase activity to 60% of the activity at atmospheric
      pressure, whereas the S. violacea RNA polymerase maintained full activity,
      indicating that the S. violacea RNA polymerase is more stable than its E. coli
      counterpart. This result was supported by the analysis of the strength of subunit
      interactions of the enzyme from both species, using a high-pressure
      electrophoresis apparatus, which showed that a pressure of 140 MPa caused
      dissociation of E. coli RNA polymerase but not that of S. violacea RNA
      polymerase. On the other hand, the core enzyme of S. violacea RNA polymerase,
      which lacked the sigma70 factor, was dissociated at 140 MPa. These results
      suggest that the sigma70 factor is required for stabilization of S. violacea RNA
      polymerase under high-pressure conditions. In this paper, we provide in vitro
      evidence for piezoadaptation at the transcriptional level, using purified RNA
      polymerase from cells of S. violacea and E. coli.

PMID- 15241659
TI  - Evidence for ditopic coordination of phosphate diesters to [Mg(15-crown-5)]2+.
      Implications for magnesium biocoordination chemistry.
AB  - The interaction of a series of phosphate diesters and triesters (1=diphenyl
      phosphate,2=dimethyl phosphate,3=bis(2-ethylhexyl) phosphate,4=trimethyl
      phosphate,5=methyldiphenyl phosphate,6=triphenyl phosphate) with [Mg(15-crown
      5)](2+) (15-crown-5=1,4,7,10,13-pentaoxocyclopentadecane) was studied as a
      simplified model for the interaction of aqueous Mg(2+) ion with phosphate
      containing biomolecules such as RNA. Using electrospray mass spectrometry, we
      confirm the formation of 1:1 adducts in the gas phase. Proton and (31)P NMR
      titration data were used to construct binding isotherms, and a 1:1 binding
      equilibrium was fit to the isotherms at room temperature to estimate the binding
      affinities. The binding affinity data are consistent with ditopic coordination of
      neutral dialkyl phosphate ligands to the [Mg(15-crown-5)](2+) unit. This involves
      inner-sphere coordination to the Mg(2+) via an oxygen atom, which is complemented
      by a weak hydrogen-bonding interaction with the crown ether ligand. Ditopic
      interaction is consistent with low-temperature NMR spectra showing four different
      configurations for1 coordinated to [Mg(15-crown-5)](2+), which are interpreted in
      terms of hindered rotation around the Mg-O(phos) bond. Thermochemical analysis of
      the binding affinity data suggests that the second-shell interaction contributes
      only about 1 kcal/mol to the binding free energy, so additional factors, such as
      steric constraints, must be operative to give a preferred phosphate orientation
      in this system. However, the experimental data do suggest that second-shell
      interactions contribute as much as 40% of the total binding energy, consistent
      with the pronounced ability of aqueous Mg(2+) to form salt-bridges linking
      secondary and tertiary elements of RNA structure.

PMID- 15241660
TI  - Platinum complexes with imino ethers or cyclic ligands mimicking imino ethers:
      synthesis, in vitro antitumour activity, and DNA interaction properties.
AB  - Both trans- and cis-[PtCl(2)(NH(3))(L)] compounds have been synthesized, L
      representing either the imino ether HN=C(OMe)Me having a Z or E configuration at
      the C=N double bond, or the cyclic ligands N = C(OMe)CH2CH2CH2 and N =
      C(Me)OCH2CH2 (compounds 1-4 for trans geometry and 5-8 for cis geometry,
      respectively). The cyclic ligands mimic the imino ether ligands but, differently
      from imino ethers, cannot undergo change of configuration. In a panel of human
      tumor cells, trans compounds inhibit growth much more than transplatin. Moreover,
      compound 1 in most cases is less active than 2, and 1 and 2 are less active than
      3 and 4, respectively. For cis compounds with imino ethers, the activity is
      reduced (5) or unaffected (6) with respect to cisplatin. Moreover, unlike trans
      compounds, substitution of cyclic ligands (7,8) for imino ethers (5,6) generally
      decreases the activity. This determines, for compounds with cyclic ligands, an
      unusual inversion of the cis geometry requirement for activity of platinum(II)
      species. Importantly,1-4 and 5-8 partially circumvent the multifocal cisplatin
      resistance of A2780cisR cells, and 1-4 also overcome resistance from reduced
      uptake of 41McisR cells. DNA interaction regioselectivity of 1-4 and 5-8 is not
      substantially modified with respect to transplatin and cisplatin. However, both
      imino ethers and cyclic ligands slow down the DNA interstrand cross-link
      reaction, ( E)-HN=C(OMe)Me and N = C(Me)OCH2CH2 decreasing also its extent.
      Therefore, DNA interaction of 1-4 and 5-8 appears to be characterized by
      persistent monoadducts (1-4), and by monoadducts and/or intrastrand cross-links
      structurally different from those of cisplatin (5-8). This study demonstrates
      that ligand configuration modulates the activity of both trans and cis compounds,
      and supports the development of platinum drugs based on their coordination
      chemistry to combat cisplatin resistance.

PMID- 15241662
TI  - Sex- and age-related differences in major depressive disorder with comorbid
      anxiety treated with fluoxetine.
AB  - OBJECTIVE: To examine sex- and age-related differences of treatment outcome in a
      cohort of outpatients with major depressive disorder (MDD), with and without
      comorbid anxiety, treated with fluoxetine. METHODS: Outpatients with a SCID
      diagnosis of MDD aged 18 to 65 years were treated openly with fluoxetine (20
      mg/day) for 8 weeks. The 17-item Hamilton Depression Rating Scale (HAM-D-17) was
      administered at baseline, and at weeks 2, 4, 6 and 8. Remission of MDD was
      defined as a HAM-D-17 score < or =7 at week 8. Rates of remission and change of
      depressive symptoms of MDD were compared among women aged < 45 years and > or =45
      years. The analyses were then repeated in men. The presence of comorbid anxiety
      disorders was included in the prediction model for change of depressive symptoms
      of MDD across age and sex. RESULTS: 176 women and 153 men were included in this
      analysis. Remission of MDD occurred in 57.1% and 50% of younger and older women
      respectively. Similar rates were present in men (57.2% and 49.1%, respectively).
      Age did not predict remission of depression or change of depressive symptoms of
      MDD, in both women and men. Anxious and non-anxious subtypes of depression did
      not present sex- or age-related differences in treatment outcome. CONCLUSION: In
      this cohort of outpatients with MDD, we observed no sex- or age-related
      differences in response to an 8-week treatment with the SSRI fluoxetine.
      Similarly, there were no age-related differences among women with anxious and non
      anxious subtype of depression.

PMID- 15241663
TI  - Binge alcohol consumption by non-alcohol-dependent women during pregnancy affects
      child behaviour, but not general intellectual functioning; a prospective
      controlled study.
AB  - Effects of binge ethanol consumption during early gestation on child
      neurodevelopment have not been elucidated. To study whether binge drinking
      affects cognitive abilities and behavior of exposed children, a prospective
      observational study comparing 51 children exposed to binge drinking during the
      first trimester of pregnancy to 51 children not exposed to any teratogens was
      conducted. The children's physical development, intelligence, language abilities
      and behavior were assessed. Temperament test results showed that children exposed
      in utero to maternal binge drinking displayed a greater degree of disinhibited
      behavior and that this behavior was associated with early drinking variables.
      Although binge alcohol drinking by non-alcohol-dependent women during the first
      trimester of pregnancy does not appear to affect intelligence or cognitive and
      language development of young children, binge drinking in pregnancy does increase
      the likelihood of certain behavioral characteristics that might predispose these
      children to later behavioral dysfunction.

PMID- 15241661
TI  - Do changes in mood and concerns about weight relate to smoking relapse in the
      postpartum period?
AB  - The majority of women who quit smoking during pregnancy will resume smoking
      during the postpartum period. Little is known, however, about the predictors of
      postpartum relapses to smoking. Changes in mood and increases in concerns about
      weight are common during the postpartum period, and these factors may affect
      women's postpartum smoking behavior. In this paper, we present a model of the
      relationship among mood, weight concerns and postpartum smoking. Data from
      previous postpartum relapse prevention trials are reviewed and evidence of a
      connection between changes in mood and weight concerns to postpartum relapse is
      presented. Directions for future research on the prevention of smoking relapses
      during the postpartum period, and the roles of mood and weight concerns in
      smoking relapse are presented.

PMID- 15241664
TI  - Influence of depressive symptomatology on maternal health service utilization and
      general health.
AB  - BACKGROUND: While postpartum depression is a well-established affective
      condition, information about its influence on health service utilization is
      scant. The objective of this study was to examine the influence of maternal mood
      on health service utilization and general health within the first 2 months
      postpartum. METHODS: As part of a population-based postpartum depression study, a
      cohort of 594 women from British Columbia completed postal questionnaires at 1,
      4, and 8 weeks postpartum. RESULTS: Women with depressive symptomatology had a
      significantly higher number of contacts with a health professional than those
      with non-depressive symptomatology. Furthermore, over 50% of high utilizers of
      family physician and public health nursing services in the first month postpartum
      exhibited depressive symptomatology. Women with depressive symptomatology were
      also significantly more likely to have lower scores on the SF-36 and to indicate
      the care they received from family physicians to be unhelpful. CONCLUSION: Health
      professionals who discover a woman frequently using health services should
      closely examine the motivation for the visits and consider screening for
      postpartum depression. Future research should examine whether screening women
      with high utilization patterns reduces unnecessary health care visits and
      facilitates early diagnosis and treatment of postpartum depression.

PMID- 15241665
TI  - The impact of depression and fluoxetine treatment on obstetrical outcome.
AB  - INTRODUCTION: This study prospectively followed women over the course of
      pregnancy to assess the impact of depression and/or antidepressant treatment on
      obstetrical outcome. METHOD: Sixty-four outpatient women with an Axis I diagnosis
      of major depressive disorder or no psychiatric history were followed in each
      trimester of pregnancy with administration of the CES-D. A subset of the women
      with depression received treatment with fluoxetine during pregnancy. Subjects
      with a CES-D score greater than 16 at any time point were further assessed for
      the presence of an active major or minor depressive episode. Primary outcome
      variables included infant gestational age, birth weight, Apgar score, and
      admission to the neonatal intensive care unit. RESULTS: Analyzable data were
      available for 62 women. No significant differences were found in outcome
      variables between those women with exposure to medication and/or prenatal
      depressed mood and those women without a history of depression. CONCLUSIONS: In
      contrast to other studies, our study did not demonstrate an adverse effect of
      fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a
      significant impact of depression during pregnancy on obstetrical outcome.

PMID- 15241666
TI  - Relational ethics: when mothers suffer from psychosis.
AB  - OBJECTIVE: The goal of this review is to aid clinicians with ethical issues
      arising in the treatment of women who suffer from psychosis. METHOD: This paper
      is a synthesis of the recent literature in adult and child psychiatry, ethics,
      law, and child welfare pertaining to the topic of maternal psychosis. Topics
      include: family planning, the care of pregnant women with schizophrenia,
      postpartum psychosis, child custody, involuntary treatment, confidentiality
      issues, and service fragmentation. CONCLUSION: Appreciation of the particularized
      circumstances of issues arising in the treatment of mothers who suffer from
      psychosis serve the clinician better than the dispassionate application of a
      principle-driven ethic.

PMID- 15241667
TI  - Smoking cessation in pregnancy.

PMID- 15241669
TI  - Predeposit autologous donation in spinal surgery: a multicentre study.
AB  - BACKGROUND: Allogeneic blood transfusions (ABT) are often necessary in elective
      spine surgery because of perioperative blood loss. Preoperative autologous blood
      donation (PABD) has emerged as the principal means to avoid or reduce the need
      for ABT. Consequently, a multicentre study was conducted to determine the yield
      and efficacy of PABD in spine surgery and the possible role of recombinant human
      erythropoietin (EPO) in facilitating PABD. METHODS: We retrospectively reviewed
      the hospital charts and blood bank records from all consecutive spine surgery
      patients who were referred for PABD. Data were obtained from two A-category
      hospital blood banks and one general hospital. Although we collected data from
      1994, the analytic study period was from the last quarter of 1995 to December
      2003. Fifty-four (7%) out of 763 patients referred for PABD were rejected, and
      medical records were available for 680 patients who were grouped into spinal
      fusion (556; 82%) and scoliosis surgery (124;18%). EPO was administered to 120
      patients (17.6%). From 1999 to 2003, PABD steadily increased from 60 to 209
      patients per year. RESULTS: Overall, 92% of the patients were able to complete
      PABD, 71% were transfused, and almost 80% avoided ABT. PABD was more effective in
      fusions (86%) than in scoliosis (47%). Blood wastage was 38%, ranging from 18%
      for scoliosis to 42% for fusions. EPO allowed the results in the anaemic patients
      to be improved. CONCLUSIONS: Therefore, despite the limitations of this
      retrospective study, we feel that PABD is an excellent alternative to ABT in
      spine surgery. However, the effectiveness of PABD may be enhanced if associated
      with other blood-saving techniques.

PMID- 15241670
TI  - Iliac crest reconstruction with a bioactive ceramic spacer.
AB  - This study aimed to investigate the long-term clinical results of the apatite
      wollastonite-containing glass ceramic (AWGC) iliac spacer and to discuss its
      efficacy in reconstruction of the bone graft donor site at the iliac crest.
      Thirty-one patients were studied for more than 10 years. All patients underwent
      anterior spinal fusion using autogenous tricortical iliac bone graft. After
      harvest of tricortical iliac bone graft, an AWGC iliac spacer ranging from 15 mm
      to 70 mm in length was press-fitted into the gap. Long-term clinical results were
      obtained from radiological and blood examinations. Thirty patients (97%) were
      satisfied with the spacer. There was new bone formation around the spacer on the
      radiograph. There was no abnormal silicon concentration in blood examinations.
      AWGC iliac spacer appears to be useful in the reconstruction of harvested iliac
      crest. New bone formation occurs, reducing the defect size.

PMID- 15241671
TI  - Neck pain and disability following motor vehicle accidents--a cohort study.
AB  - The primary aim of the study was to compare the prevalence of neck pain and
      disability in a group exposed to motor vehicle accidents (MVAs) with those in the
      general population. The secondary aim was to assess the prevalence of a past
      history of exposure to an MVA with sequelae of neck pain in the general
      population. The exposed group consisted of 121 patients with neck complaints
      following an MVA in 1983. The control group, consisting of 1,491 subjects, was
      randomly selected, with attention to the distribution of age and gender in the
      exposed group. A neck-pain questionnaire was mailed to the subjects. In the
      control group, it included enquiry about a history of exposure to an MVA with
      sequelae of neck pain. The Neck Disability Index (NDI) was used to assess neck
      related disability. In the exposed group 108 subjects (89%) responded, and in the
      control group 931 (62%) did. Seventeen years after the MVA, 59 subjects (55%)
      reported neck pain in the exposed group, with no gender differences. In the
      control group 270 (29%) reported neck pain with a higher frequency among women
      (34%) than men (19%) (p<0.01). There was a significant difference between the
      exposed group and the control group regarding the occurrence of neck pain
      (p<0.001). In the control group 34% recalled a history of an MVA, among whom one
      third reported neck pain in connection with the accident and 28% had persistent
      neck pain referable to the accident. The exposed group scored significantly
      higher on the NDI (p<0.001) and reported significantly higher neck pain intensity
      than did the control group (p<0.001). In conclusion, a past history of exposure
      to an MVA with sequelae of neck pain appears to have a substantial impact on
      future persistent neck pain and associated disability.

PMID- 15241672
TI  - [Pain symptoms of osteoarthritis-aspects of etiology and therapy].
AB  - Due to demographic changes and associated socioeconomic problems osteoarthritis
      is of increasing value. Simultaneously there are more and more older people who
      want to practice sports. Pain symptoms of osteoarthritis can be positively
      influenced by paracetamol and NSAR, in combination with orthopedic aids and
      physical therapy in early stages. Apart from these established pain-therapeutic
      procedures as well as first evident results of osteoarthritis modifying drugs,
      gene-therapy offers promising approaches that will have to be confirmed in
      further studies. In case of failure of conservative treatment there are several
      surgical options. Arthroscopic surgery mostly offers pain reduction only for a
      short period of time. A slower progression of osteoarthritis in the long run can
      only be achieved by osteotomy provided the right indication. Ultimately joint
      replacement exists as a reliable and successful treatment option in hip, knee and
      shoulder surgery.

PMID- 15241673
TI  - Current management of infants with fetal renal pelvis dilation: a survey by
      French-speaking pediatric nephrologists and urologists.
AB  - To analyze the current management recommendations among French-speaking
      physicians treating infants with antenatal renal pelvis dilatation, we surveyed
      83 pediatric nephrologists and 68 pediatric urologists by questionnaire. A total
      of 45 (54%) pediatric nephrologists and 38 (56%) pediatric urologists responded.
      The threshold for the diagnosis of abnormal fetal renal pelvis dilatation was
      significantly higher among pediatric urologists than nephrologists. All
      responders perform renal ultrasound examinations after birth. Postnatal renal
      pelvis dilatation was considered abnormal if the anteroposterior diameter was
      >/=11+/-1.9 mm by the pediatric urologists and >/=9+/-2.9 mm by the pediatric
      nephrologists ( P=0.003). Pediatric urologists were more likely than
      nephrologists to recommend routine voiding cystourethrography [41% versus 20% (
      P=0.04)]. Mercaptoacetyl-triglycine renography was the most routinely used tool
      to achieve functional evaluation during follow-up among the responders. Pediatric
      urologists were more likely to recommend surgical treatment in dilated kidneys
      with initial function <40%. In conclusion, pediatric urologists had significantly
      higher thresholds for the detection of prenatal and neonatal renal pelvis
      dilatation. They also more frequently recommended routine voiding
      cystourethrography and surgical therapy of dilated kidneys with low function than
      pediatric nephrologists. The variability in attitudes is most probably due to the
      absence of clear guidelines based on prospective and controlled trials.

PMID- 15241674
TI  - Power Doppler ultrasonography in the diagnosis of acute childhood pyelonephritis.
AB  - In the absence of specific symptomatology in children, the early diagnosis of
      acute pyelonephritis (APN) is a challenge, particularly during infancy. In an
      attempt to differentiate APN from lower urinary tract infection (UTI), we
      evaluated the ability of power Doppler ultrasonography (PDU) to predict renal
      parenchymal involvement, as assessed by dimercaptosuccinic acid ((99m )Tc-DMSA)
      scintigraphy. The study comprised 62 patients, 46 girls and 16 boys, aged 2 weeks
      to 5 years, admitted to the pediatric department with febrile UTI. All children
      were examined by PDU and DMSA scintigraphy within the first 3 days of admission.
      In the group of 31 patients with one or more DMSA scan abnormalities, the PDU
      showed a matching perfusion defect in 27 (87%). Of 26 children with normal DMSA
      scintigraphy, the PDU evaluation was also normal in 24. The sensitivity and
      specificity of PDU for the detection of affected kidneys were 87% and 92.3%, and
      the positive predictive value and negative predictive value were 93.1% and 85.7%,
      respectively. These data indicate the PDU has a high sensitivity and specificity
      for differentiating APN from lower UTI and may be a useful and practical tool for
      the diagnosis of APN in infants and children.

PMID- 15241675
TI  - Anemia in pediatric dialysis patients in end-stage renal disease network 5.
AB  - To identify demographic and clinical characteristics associated with failure to
      achieve hemoglobin levels >/=11 g/dl in prevalent pediatric end-stage renal
      disease (ESRD) patients, a cross-sectional analysis of patient clinical data
      collected by the Mid-Atlantic Renal Coalition in conjunction with the 2000 and
      2001 ESRD Clinical Performance Measures Projects was performed. Ninety-nine
      patients (mean age 12.6 years, SD 5.4) contributed 119 observations to this
      analysis. Of patients on hemodialysis, 36.6% were anemic, and 39.5% of patients
      on peritoneal dialysis (PD) were anemic. Associations between age, race, gender,
      assigned cause of ESRD, Kt/V, transferrin saturation, time on dialysis, serum
      albumin, dialysis modality, and the achievement of target hemoglobin were
      examined. In multivariate logistic regression analyses examining age, dialysis
      modality, time on dialysis, and serum albumin, each 1-year increase in age was
      significantly associated with hemoglobin levels <11 g/dl [adjusted odds ratio
      (OR) 1.18, 95% confidence interval (CI) 1.06-1.32] and PD patients were more than
      twice as likely to have hemoglobin levels <11 g/dl (adjusted OR 2.62, 95% CI 0.98
      7.04). Patients on dialysis for 6 months or more were less likely to be anemic
      than those on dialysis for less than 6 months (adjusted OR 0.39, 95% CI 0.16
      0.99). In conclusion, increasing age, dialysis for less than 6 months, and
      treatment with PD were predictive of anemia in this population.

PMID- 15241676
TI  - Co-administration of cyclosporine and ketoconazole in idiopathic childhood
      nephrosis.
AB  - The concomitant use of cyclosporine (CsA) and ketoconazole (keto) in children
      with nephrotic syndrome (NS) has never been reported in the literature. This
      retrospective cohort study was conducted to investigate cost saving, safety, and
      efficacy of co-administration of keto and CsA in children with NS. The study
      included 186 nephrotic children receiving CsA therapy. Most were steroid
      dependent or resistant, and the most common pathology was focal segmental
      glomerulosclerosis (62%). Among our patients, 137 received daily keto therapy
      (keto group) 50 mg/day in addition to CsA, while 49 received CsA alone (non-keto
      group). The characteristics of both groups were comparable and the mean (+/-SD)
      duration of treatment was 22.9 +/- 8.1 months. Co-administration of keto
      significantly reduced the mean dose of CsA with an overall net cost saving of
      37%. It also resulted in a significant improvement of CsA response, more
      successful steroid withdrawal, and decreased the frequency of renal impairment.
      Keto was generally well tolerated and safe. We conclude that co-administration of
      low-dose keto with CsA in children with idiopathic NS is safe, significantly
      reduces the cost of CsA therapy, and may improve the patient outcome.

PMID- 15241677
TI  - Altered gating properties of functional Cx26 mutants associated with recessive
      non-syndromic hearing loss.
AB  - Connexins (Cx) form gap junctions that allow the exchange of small metabolites
      and ions. In the inner ear, Cx26 is the major gap junction protein and mutations
      in the Cx26-encoding gene, GJB2, are the most frequent cause of autosomal
      recessive non-syndromic hearing loss (DFNB1). We have functionally analyzed five
      Cx26 mutations associated with DFNB1, comprising the following single amino-acid
      substitutions: T8M, R143W, V153I, N206S and L214P. Coupling of cells expressing
      wild-type or mutant Cx26 was measured in the paired Xenopus oocyte assay. We
      found that the R143W, V153I and L214P mutations were unable to form functional
      channels. In contrast, the T8M and N206S mutants did electrically couple cells,
      though their voltage gating properties were different from wild-type Cx26
      channels. The electrical coupling of oocytes expressing the T8M and N206S mutants
      suggest that these channels may retain high permeability to potassium ions.
      Therefore, deafness associated with Cx26 mutations may not only depend on reduced
      potassium re-circulation in the inner ear. Instead, abnormalities in the exchange
      of other metabolites through the cochlear gap junction network may also produce
      deafness.

PMID- 15241678
TI  - A novel splice acceptor mutation in the DSPP gene causing dentinogenesis
      imperfecta type II.
AB  - The dentin sialophosphoprotein (DSPP) gene (4q21.3) encodes two major
      noncollagenous dentin matrix proteins: dentin sialoprotein (DSP) and dentin
      phosphoprotein (DPP). Defects in the human gene encoding DSPP cause inherited
      dentin defects, and these defects can be associated with bilateral progressive
      high-frequency sensorineural hearing loss. Clinically, five different patterns of
      inherited dentin defects are distinguished and are classified as dentinogenesis
      imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II. The
      genetic basis for this clinical heterogeneity is unknown. Among the 11 members
      recruited from the studied kindred, five were affected with autosomal dominant
      DGI type II. The mutation (g.1188C-->G, IVS2-3C-->G) lay in the third from the
      last nucleotide of intron 2 and changed its sequence from CAG to GAG. The
      mutation was correlated with the affection status and was absent in 104
      unaffected individuals (208 alleles) with the same ethnic and geological
      background. The proband was in the primary dentition stage and presented with
      multiple pulp exposures. The occlusal surface of his dental enamel was generally
      abraded, and the dentin was heavily worn and uniformly shaded brown. The dental
      pulp chambers appeared originally to be within normal limits without any sign of
      obliteration, but over time (by age 4), the pulp chambers became partially or
      completely obliterated. The oldest affected member (age 59) showed mild hearing
      loss at high-frequency (8 kHz). Permanent dentition was severely affected in the
      adults, who had advanced dental attrition, premature loss of teeth, and extensive
      dental reconstruction.

PMID- 15241679
TI  - Identification of a novel type 1 diabetes susceptibility gene, T-bet.
AB  - The gene encoding interferon (IFN)-gamma, IFNG, is known as one of the candidate
      susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN
      gamma, play important roles in the pathogenesis of type 1 diabetes. Therefore, we
      focused on the Th1-specific T-box transcription factor gene (T-bet), which
      contributes to the induction of the hallmark Th1 cytokine, IFN-gamma. We first
      screened for polymorphisms in the T-bet gene and detected two microsatellite
      repeat polymorphisms located in intron 1 and the 3'- flanking region, and two
      single nucleotide polymorphisms, including a His33Gln substitution within the
      coding region. By association studies, the Gln-positive phenotype and (CA)14
      allele in 3'-flanking region of T-bet were found to be associated with type 1
      diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a
      significantly higher transcriptional activity of the IFNG gene via a dual
      luciferase reporter assay. Our study suggests the first evidence of an
      association between type 1 diabetes and polymorphisms in the T-bet gene, and that
      variation in T-bet transcriptional activity may play a role in the development of
      type 1 diabetes, possibly through the effect on IFN-gamma production in Th1
      cells.

PMID- 15241680
TI  - Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.
AB  - Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined
      molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G,
      encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor
      receptor type 3 gene (FGFR3). This frequently occurs as a new mutation,
      manifesting one of the highest documented rates for any transversion in the human
      genome. To understand the biology of this mutation, we have investigated its
      parental origin, and the ages of the parents, in 19 families with de novo
      c.749C>G mutations. All ten informative cases originated from the paternal allele
      (95% confidence interval 74-100% paternal); the average paternal age at birth
      overall was 34.7 years. An exclusive paternal origin of mutations, and increased
      paternal age, were previously described for a different mutation (c.1138G>A) of
      the FGFR3 gene causing achondroplasia, as well as for mutations of the related
      FGFR2 gene causing Apert, Crouzon and Pfeiffer syndromes. We conclude that
      similar biological processes are likely to shape the occurrence of this c.749C>G
      mutation as for other mutations of FGFR3 as well as FGFR2.

PMID- 15241681
TI  - Mutational analysis of genes encoding chromatin proteins in the archaeon
      Methanococcus voltae indicates their involvement in the regulation of gene
      expression.
AB  - Several genes for chromatin proteins are known in Archaea. These include histones
      and histone-like proteins in Euryarchaeota, and a DNA binding protein, Alba,
      which was first detected in the crenarchaeote Sulfolobus solfataricus and is
      thought to be involved in transcriptional regulation. The methanogenic archaeon
      Methanococcus voltae harbors four genes coding for all these three types of
      chromatin proteins. Deletion mutants for the two histone genes ( hstAand hstB),
      the gene encoding the histone-like protein ( hmvA) and the gene for the Alba
      homologue ( albA) have now been constructed in this organism. Although all single
      mutants were viable, deletion of hstA resulted in slow growth. Two transcripts
      were detected for each of the two histone genes. These were expressed in
      different relative amounts, which were correlated with different growth phases.
      Cell extracts obtained from the different mutants exhibited altered protein
      patterns, as revealed by 2D gel electrophoresis, indicating that the chromatin
      proteins are involved in gene regulation in M. voltae.

PMID- 15241682
TI  - Cold induction of the Bacillus subtilis bkd operon is mediated by increased mRNA
      stability.
AB  - Recently it has been demonstrated that the ptb - bcd - buk - lpdV - bkdAA - bkdAB
      - bkdB operon ( bkdoperon) of Bacillus subtilis, which encodes the enzymes that
      catalyze the degradation of branched-chain amino acids, is inducible by a
      temperature downshift from 37 to 18 degrees C. Deamination and oxidative
      decarboxylation of isoleucine generates 2-methyl-butyryl-CoA, which serves as the
      precursor of anteiso-branched fatty acid species. Most probably, the induction of
      this operon upon cold shock ensures an increase in the content of anteiso
      branched fatty acids in the membrane lipids at low temperature, thus permitting
      maintenance of membrane fluidity at lower temperatures. In the present study, we
      have analyzed the mechanism of cold induction of the bkd operon and of four
      further cold-inducible transcriptional units in B. subtilis. We demonstrate that
      cold induction of these genes is mediated by an increase in the stability of the
      corresponding mRNAs. None of the promoters that control the five transcriptional
      units analyzed is actually cold-inducible. Furthermore, the results of this study
      indicate that the 5' leader regions are not involved in the cold-induced
      stabilization of the mRNAs. The structural elements that enhance mRNA stability
      must therefore be restricted to the 3'-ends and/or the coding regions.

PMID- 15241683
TI  - Variable effects of beta-carotene therapy in a child with erythropoietic
      protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an inborn error of heme biosynthesis with
      high levels of protoporphyrin in red cells and is characterized by mild to
      moderate photosensitivity. High-dose beta-carotene therapy has been reported to
      afford photoprotection in patients with EPP. We report the case of a 5-year-old
      Caucasian female with EPP who presented with a long-standing 3-year history of
      recurrent facial blisters and erythematous swelling and lesions of other sun
      exposed areas of the skin. She was treated with a topical sunblocker (PreSun
      Ultra-SP45) but continued to show moderate to severe photosensitivity despite 3
      months (March to May) of vigorous photoprotection. She was then started on
      increasing doses of beta-carotene (90-180 mg/day) over a period of 3 months (June
      to September) which resulted in a marked improvement of both facial and forearm
      lesions, but only modest improvement in her hand lesions. CONCLUSION: High-dose
      beta-carotene appears to provide photoprotection in erythropoietic
      protoporphyria, resulting in improved but highly variable tolerance to sunlight.

PMID- 15241684
TI  - Maternal phenylketonuria: the French survey.
AB  - We report the French experience regarding pregnancies in maternal phenylketonuria
      (PKU). In 2001, a questionnaire was sent to each referring PKU specialist in the
      20 centres of each region of France, collecting reports on 135 pregnancies in 79
      women born between 1958 and 1980. The majority of the 135 pregnancies occurred
      after 1990. A total of 42 women were informed of the risks of untreated
      pregnancy, while 26 were not informed (no data for 11). A strict diet was
      achieved in 83% of informed and in 16% of uninformed mothers prior to conception.
      Healthy offspring were observed in 43% of the 135 pregnancies, spontaneous
      abortions in 10.4%, elective abortions in 4.4%, therapeutic abortions in 12.6%,
      and embryopathies (EP) in 21.5%. In 8.1% of cases, the outcomes (in earliest
      pregnancies) are unknown. The proportion of healthy children increased over time
      and reached 80% of the pregnancies of informed females. There were seven heart
      defects, all in cases of EP, but although microcephaly and intrauterine growth
      retardation (IUGR) were almost constant in EP, we also found nine healthy
      children with IUGR. A continuum between EP and healthy children is suggested. The
      anthropometric data of the mothers showed that their body mass index (BMI)
      distribution was shifted to the left compared to women of the general population.
      This lower BMI and poor weight gain during pregnancy could contribute to the IUGR
      observed in normal babies whose mothers received a phenylalanine-restricted diet
      during pregnancy. CONCLUSION: the information and the preconception diet are
      effective for avoiding embryopathies in maternal phenylketonuria. Nutritional
      parameters can influence fetal growth and the nutritional state must be closely
      monitored throughout pregnancies of women with phenylketonuria.

PMID- 15241685
TI  - Clinical and biochemical manifestations of syndrome X in obese children.
AB  - The aim of this study was to investigate whether the clinical and metabolic
      characteristics of syndrome X had their onset in childhood in otherwise healthy
      but obese children of Greek origin. A group of 25 obese children and 18 age- and
      sex matched control subjects, aged 6-14 years, underwent an oral glucose
      tolerance test (OGTT), assessed for determination of plasma glucose and insulin
      levels. Insulin sensitivity and insulin resistance were estimated by mathematical
      models using calculations obtained during the OGTT. Body mass index (BMI) and
      blood pressure were measured, as well as serum lipoprotein and aminotransferase
      concentrations, after an overnight fast. The obese children had significantly
      higher blood pressure (systolic and diastolic) (P<0.001), triglycerides,
      lipoprotein(a) and alanine aminotransferase levels (P<0.05) and significantly
      lower HDL-cholesterol and apolipoprotein A-1 values (P<0.001). Plasma glucose
      levels during the OGTT were similar in both obese children and control subjects,
      while plasma insulin levels were significantly higher in obese children (P<0.01).
      In mathematical models, mean values of insulin sensitivity predictors: metabolic
      clearance rate and insulin sensitivity index were significantly lower in obese
      children (P<0.001). Predictors of beta-cell function: insulin resistance index
      and insulin release index were significantly higher in obese children (P<0.001).
      CONCLUSION: Childhood adiposity was associated with all traditional components of
      syndrome X. The early recognition of these factors as predisposing elements of
      the appearance of metabolic syndrome requires the development of strategies to
      manage excess weight gain during childhood, with the ultimate goal being the
      prevention of type 2 diabetes and cardiovascular disease in adulthood.

PMID- 15241686
TI  - Early postnatal skin colour changes in term newborns with subclinical
      histological chorioamnionitis.
AB  - Chorioamnionitis, a known risk factor for fetal and neonatal morbidity both in
      preterm and term newborns, is often subclinical. Earlier observations have linked
      skin colourimetry to neonatal illness severity and adverse neonatal outcome.
      Here, we tested the hypothesis that subclinical histological chorioamnionitis is
      associated with early postnatal skin colour changes in term newborns. Skin
      colourimetry on ten body sites (forehead, cheek, forearm, palm, upper chest,
      abdomen, back, buttock, leg, and sole) was examined in 45 term infants with
      subclinical histological chorioamnionitis and 45 sex- and gestational age-matched
      controls, using a tristimulus portable colourimeter at 1, 5 and 10 min after
      birth. Infants with subclinical histological chorioamnionitis showed
      statistically significant early postnatal skin colourimetric differences, in nine
      and seven out of the ten body sites examined as compared to control newborns at 1
      min (P< or =0.0092), 5 min (P< or =0.0081) and 10 min (P< or =0.0056) from birth,
      respectively. Skin colourimetry changes were associated with lower 1 min Apgar
      scores (P<0.0001), cord blood pH (P<0.0001), PaO2 (P<0.0001), and base excess
      (P<0.0001) values, together with higher cord blood PaCO2 (P=0.0001), NICU
      admissions (P=0.00076), endotracheal intubation in the delivery room (P=0.012),
      Neonatal Acute Physiology-Perinatal Extension (P<0.0001) and Neonatal Therapeutic
      Intervention Scoring System (P<0.0001) scores than the chorioamnionitis-negative
      infants. CONCLUSION: These findings, compatible with early peripheral
      microcirculatory changes, indicate skin vasoconstriction as an early neonatal
      manifestation of subclinical chorioamnionitis.

PMID- 15241687
TI  - A 7-year study of bloodstream infections in an English children's hospital.
AB  - Knowledge of the pattern of bloodstream infection (BSI) can help determine
      antibiotic prescribing policy and infection control procedures. Data on 2364
      consecutive episodes of BSI at Birmingham Children's Hospital over 7 years were
      collected prospectively. A total of 1224 (51.8%) episodes were community
      acquired, but only 281 (11.9%) were in previously healthy children. Intravascular
      devices (IVDs) were the most common source of infection, accounting for 48.9% of
      episodes. Gram-positive, gram-negative and anaerobic bacteria accounted for
      66.2%, 31.3% and 0.4% of isolates, and 2.2% were yeasts. Coagulase-negative
      staphylococci, Staphylococcus aureus and enterococci accounted for over 50% of
      all isolates. Of these, only enterococci were predominantly hospital-acquired.
      Neisseria meningitidis was the most common cause of community-acquired BSI in
      previously healthy children. Of cases of meningococcaemia, 55.6% were diagnosed
      by PCR alone. Antibiotic resistance, especially in Enterobacteriaceae, S. aureus
      and enterococci, was more common than in earlier studies of BSI in children, and
      varied between specialties. The overall mortality rate directly attributable to
      infection was 2.4%, but was higher in neonates (6.2%) and in previously healthy
      children with community-acquired infections (5.3%). CONCLUSION: Intravascular
      devices have emerged as the commonest source of bloodstream infection in
      children, leading to marked similarities in the species distribution of blood
      culture isolates across specialties other than General Paediatrics, and
      explaining the low overall mortality rate. Antibiotic resistance was found
      frequently in most commonly isolated pathogens, but differences between
      specialties suggest the existence of local risk factors, some of which might be
      amenable to infection control interventions.

PMID- 15241689
TI  - Unsuspected Kingella kingae infections in afebrile children with mild skeletal
      symptoms: the importance of blood cultures.

PMID- 15241688
TI  - Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use
      of pamidronate as rescue therapy.
AB  - Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant condition
      due to heterozygous loss of function calcium sensing receptor (CaSR) mutations.
      However, individuals who are homozygous for CaSR mutations have neonatal severe
      hyperparathyroidism (NSHPT), which unlike the relatively benign and asymptomatic
      FHH can be fatal without parathyroidectomy. We report three patients with NSHPT
      associated with marked hypercalcaemia and severe hyperparathyroidism with related
      skeletal demineralisation. We describe the novel use of intravenous pamidronate
      in NSHPT, to control severe hypercalcaemia in these patients prior to
      parathyroidectomy and in one individual as a rescue therapy to stabilise life
      threatening demineralisation. Furthermore, a marked phenotypic heterogeneity was
      observed amongst four members from a large kindred with the same homozygous CaSR
      mutations: one patient would have died without parathyroidectomy in infancy; a
      second patient survived infancy but underwent parathyroidectomy in early
      childhood following severe symptomatic hypercalcaemic episodes; whilst the other
      two patients have survived to adolescence without parathyroidectomy.
      Additionally, in contrast to the literature these two individuals suffered
      minimal morbidity. CONCLUSION: We commend the short-term use of pamidronate in
      neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt
      hyperparathyroid-driven skeletal demineralisation in preparation for
      parathyroidectomy. The remarkable degree of phenotypic variation demonstrated
      remains unexplained without functional studies; this variability highlights the
      challenge of treating this rare condition.

PMID- 15241692
TI  - Presentation of a dummy representing suit for simulation of huMAN heatloss
      (DRESSMAN).
AB  - DRESSMAN designates a novel dummy for climate measurements that allows predicting
      the human thermal comfort experienced inside rooms (buildings, vehicles,
      aircraft, railway compartments etc.) on the basis of indoor climate measurements.
      Measurements can be listed in tabular form and can also be represented by way of
      color gradations in a virtual 3D human model. Optionally, visualization may be
      rendered during or after measurement. Due to its very quick response, DRESSMAN is
      particularly suited for nonstationary processes.

PMID- 15241691
TI  - Effects of strength, endurance and combined training on myosin heavy chain
      content and fibre-type distribution in humans.
AB  - This study investigated the effect of strength training, endurance training, and
      combined strength plus endurance training on fibre-type transitions, fibre cross
      sectional area (CSA) and MHC isoform content of the vastus lateralis muscle.
      Forty volunteers (24 males and 16 females) were randomly assigned to one of four
      groups: control (C), endurance training (E), strength training (S), or concurrent
      strength and endurance training (SE). The S and E groups each trained three times
      a week for 12 weeks; the SE group performed the same S and E training on
      alternate days. The development of knee extensor muscle strength was S>SE>E (
      P<0.05) and has been reported elsewhere. The reduction in knee extensor strength
      development in SE as compared to S corresponded to a 6% increase in MHCIIa
      content ( P<0.05) in SE at the expense of the faster MHCIId(x) isoform ( P<0.05),
      as determined by electrophoretic analyses; reductions in MHCIId/x content after S
      or E training were attenuated by comparison. Both S and SE induced three- to
      fourfold reductions ( P<0.05) in the proportion of type IIA/IID(X) hybrid fibres.
      S also induced fourfold increases in the proportion of type I/IIA hybrid fibres
      within both genders, and in a population of fibres expressing a type I/IID(X)
      hybrid phenotype within the male subjects. Type I/IIA hybrid fibres were not
      detected after SE. Both S and SE training paradigms induced similar increases (16
      19%, P<0.05) in the CSA of type IIA fibres. In contrast, the increase in CSA of
      type I fibres was 2.9-fold greater ( P<0.05) in S as compared to SE after 12
      weeks. We conclude that the interference of knee extensor strength development in
      SE versus S was related to greater fast-to-slow fibre-type transitions and
      attenuated hypertrophy of type I fibres. Data are given as mean (SEM) unless
      otherwise stated.

PMID- 15241693
TI  - Fatigue and optimal conditions for short-term work capacity.
AB  - There is an optimal load and corresponding velocity at which peak power output
      occurs. It is reasonable to expect that these conditions will change as a result
      of fatigue during 30 s of all-out cycling. This study evaluated optimal velocity
      after 30 s of maximal isokinetic cycle ergometer exercise and tested the
      hypothesis that progressive adjustment of velocity (optimized) during 30 s of all
      out cycling would permit greater short-term work capacity (STWC). Non-fatigued
      optimal cadence [NF(OC), 109.6 (2.5) rpm] was determined for ten males on an SRM
      ergometer using regression analysis of the torque-angular velocity relation
      during a 7-s maximal acceleration. Fatigued optimal cadence [73.4 (2.4) rpm] was
      determined in the same way, immediately after a 30-s isokinetic test at NF(OC). A
      subsequent trial with cadence decreasing in steps from NF(OC) to a conservative
      estimate of fatigued optimal cadence [83.9 (2.8) rpm] was completed to see if
      more work could be done with a more optimal cadence during the test. STWC was not
      different ( P=0.50) between the constant [23,681 (764) J] and optimized [23,679
      (708) J] conditions. Another more radical progressive change in cadence with four
      subjects yielded the same result (no increase in STWC). Extraneous factors
      apparently contribute more to variability in STWC than differences between
      constant and adjusted optimization of conditions.

PMID- 15241694
TI  - Fagerstrom test for nicotine dependence: reliability in a Turkish sample and
      factor analysis.
AB  - Fagerstom Test for Nicotine Dependence (FTND) has often been used as a measure of
      physical dependence on nicotine. In this study, we aimed to verify the usefulness
      of FTND and Heaviness of Smoking Index (HSI) in a sample of Turkish smokers and
      present relationship among interrelated items in our Turkish version of FTND by
      factor analysis. One hundred sixty nine smokers, 104 (61.5%) males, 65 (38.5%)
      females smoker were administered the Turkish translation of FTND. Fifty-two
      current smokers selected randomly from 169 were administered the questionnaire
      for test- retest reliability analysis. The Turkish version of FTND had moderate
      reliability (Cronbach alpha: 0.56). One FTND item (question 3: hate- most to give
      up) performed poorly on construct reliability tests. Factor 1 was loaded by
      questions 1 (first cigarette after awakening), 4 (number of cigarettes per day),
      5 (smoking status during the first hours), 6 (smoking if ill), 2 (refrain from
      smoking in forbidden places) and factor 2 was separately loaded by question 3.
      Question 3 did not have significant correlation with the total score and the
      response to this question was significant between test and retest. The Turkish
      version of FTND may become a measuring tool in the assessment of smoking
      cessation programs. However, question 3 must be used attentively and preferably
      an explanation should be made to enable a clear understanding of the question to
      the Turkish smokers as they take the test.

PMID- 15241695
TI  - Use of acute phase proteins in pleural effusion discrimination.
AB  - The differentiation between exudates and transudates is fundamental when
      investigating the cause of pleural effusions. Acute-phase proteins could be
      potentially useful markers in this discrimination. In the attempt to define
      diagnostic criteria for the differentiation of pleural exudates from transudates,
      we measured alpha 1 acid glycoprotein, C-reactive protein, haptoglobin,
      ceruloplasmin and transferrin in pleural effusions and serum in patients with
      pleural effusions of various etiologoies. We measured the concentrations of the
      above proteins in the serum and pleural fluid of 80 (54 exudate, 26 transudate)
      consecutive patients by immunoturbidometrical methods. Pleural effusion acute
      phase proteins were elevated in the patients with exudate compared to patients
      with transudate (p< 0.001 for all). In receiver operator characteristic analysis
      showed that pleural fluid ceruloplasmin levels and the ratio pleural fluid/serum
      transferrin were superior to the others. Using the optimum cut-off point of 0.16
      g/L pleural fluid ceruloplasmin achieves a sensitivity of 92% with a specificity
      of 85%. In addition to, the optimum cut-off point for pleural fluid/serum
      transferrin ratio was 0.4 with sensitivity and specificity of 92% and 80%. When
      using together these parameters sensitivity and specificity were increased (95%,
      85%). In differential diagnosis, none of these proteins were significantly
      different in subgroups of pleural exudate. We conclude that when using together
      ceruloplasmin levels in pleural fluid and the ratio of pleural to serum
      transferrin have a high sensitivity and specificity in discrimination of
      exudative pleural effusions.

PMID- 15241696
TI  - [Familial history of cancer and lung cancer].
AB  - There are many studies supporting the family history in lung cancer. In this
      study, we observed 1500 with lung cancer cases diagnosed between the years 1995
      2000 in our clinic, and investigated family tendency of lung cancer in a control
      group including partners of 600 patients with family history of cancer. We
      conducted face-to-face interviews with 100 patients with lung cancer, and with
      first degree relatives of the other 1400 patients with lung cancer. There were
      600 positive family history of cancer. Control populations were matches of the
      cancer patients with positive family history of cancer. Cases and controls were
      asked to report on their family history of cancer, as well as smoking status of
      family members. In conclusion, in 40% of 1500 patients with lung cancer, there
      was positive family history of lung cancer with regard to malignity. This
      positive family history of cancer was consisted of 51.8% lung cancer, 35.5%
      digestive cancer and 12.7% other cancers such as breast, larynx, prostate and
      bone. In control group, the value of the positive family history of lung cancer
      with regard to malignity was 5.0% (p< 0.001). These results support the
      hypothesis of a genetic susceptibility by showing that the patients with lung
      cancer have significantly more positive family history of lung cancer and
      digestive cancer.

PMID- 15241697
TI  - [Evaluation of 105 cases with tuberculous pleurisy].
AB  - Tuberculous pleurisy has still importance in the group of exudative pleurisy. In
      this study we aimed to evaluate clinical, radiological, biochemical,
      bacteriological and histopathological findings of 105 cases with tuberculous
      pleurisy retrospectively, between January 1999 and December 2002. Female/male
      ratio was approximately 1/9 and mean age was 32.6 (range: 15-68). The common
      symptoms were chest pain (75.2%), cough (54.3%) and dyspnea (47.6%). In 17% cases
      parenchymal lesions were seen in the chest radiography while parenchymal lesions
      were found 52% of patients by computed tomography. Adenosine deaminase levels in
      pleural fluid were high in 80% of cases. PPD reactions was found positive in
      84.7% of case. Sputum was studied in 52 cases. In 6 (11.5%) patients both ARB and
      culture were positive but in 4 (7.7%) patients was only culture positive. Pleural
      fluid ARB examination of all patients was negative whereas culture was positive
      only in 5 (5%) of patients. In two patients pleural biopsy material culture was
      positive for ARB. Cytological examination of pleural fluid revealed lymphocyte
      predominance in 81 (81%) of cases. Eighty one patients had pleural biopsy and
      pathologic evaluation revealed tuberculosis in 59 (73%) of them. At the end of
      the treatment 24 (23%) patients had pleural thickening. Pleural fluid LDH level
      of the patients with pleural thickening was higher than the other patients
      significantly (p=0.024). It is concluded that, pleural biopsy is the most
      effective diagnostic method for the tuberculous pleurisy and in the patient with
      elevated pleural LDH level, pleural thickening seems more.

PMID- 15241698
TI  - [The value of bronchial lavage in patients with radiologically suggestive
      pulmonary tuberculosis with no sputum production and gastric lavage smear
      negativity].
AB  - We assessed whether acid-fast bacilli (AFB) investigation in bronchial lavage
      (BL) contributes to diagnosis in patients with gastric lavage smear negative and
      radiologically suggestive of pulmonary tuberculosis. Eighty-three patients were
      recruited for the study, five cases were excluded due to diagnosis of inactive
      disease or non-tuberculosis disease. The remaining 78 patients were evaluated.
      All patients were unable to expectorate sputum and their gastric lavages were
      negative for AFB. BL was performed for the detection of Mycobacterium
      tuberculosis in all patients. Bronchial lavage smear were positive in 15.4%(12
      patients). BL culture positivity was 58.3%(42 patients) and gastric lavage
      culture positivity was 33.3%(26 patients). Eighteen cases had both gastric lavage
      and BL culture positivity. BL culture was positive in 24 cases who had gastric
      lavage culture negativity. We suggest that in cases who do not produce sputum and
      whose gastric lavage smears are negative; BL should be performed for diagnosis of
      pulmonary tuberculosis.

PMID- 15241699
TI  - [Clinical features of non-small cell lung cancer cases].
AB  - The aim of this study was to evaluate the clinical features of non-small cell
      lung cancer (NSCLC) cases that were diagnosed in our clinic. The patients who
      were diagnosed as NSCLC in our clinic between January 1988 and January 1999 were
      comprised the study group. The files and records of the study group were
      retrospectively reviewed to identify patients and all the data including
      demographic characteristics, history, physical examination findings, laboratory
      values, diagnostic procedures, radiologic findings and staging procedures. The
      study group included 564 patients (506 male, 58 female). The mean age was 60
      years (28-97). 87% of the patients were current smokers or ex-smokers. The most
      frequent symptoms on admission were cough, sputum, and dyspnea. The most common
      radiologic finding was a central mass with a diameter of more than 4 cm with an
      irregular border. The diagnosis was established by histopathologic examination of
      biopsy specimens obtained by various means, in which bronchoscopy was the sole
      means of diagnosis in 83% of the patients. Histopathologic examination of the
      biopsy specimens resulted as follows: 85.8% squamous cell carcinoma, 10.3%
      adenocarcinoma, 1.4% large cell carcinoma, 0.45% adenosquamous carcinoma, and
      2.1% undifferentiated NSCLC. Staging procedures that were done in all patients
      revealed that 85% of the patients were diagnosed at the stage IIIB and IV.
      Metastasis was most frequently to the bones followed by brain and liver. In our
      study squamous cell carcinoma was the most common histopathologic type with a
      higher percentage than the previous reports in the literature. The percentages of
      stage IIIB and IV were also higher in our study than previous papers in the
      literature.

PMID- 15241700
TI  - [Evaluation of spirometric and pulmonary haemodynamic parameters in patients with
      COPD].
AB  - In this study we aimed to asses the association between the spirometric test
      which is known to be an indicator of severity of the disease and pulmonary artery
      pressure, in patient chronic obstructive pulmonary disease (COPD). Study
      population consisted of 51 patients with COPD. Severity of the disease was graded
      by the criteria of European Respiratory Society; mildly obstructive 5 patients
      (FEV1 > 70%), moderately obstructive 10 (FEV1= 50-69%), severely obstructive 36
      patients (FEV1 < 50%). Measurement of pulmonary artery pressure was performed bt
      microcatheterisation method. Statistical analysis was performed between two
      groups; group I consisted of mildly and moderately obstructive patients, and
      group II severely obstructive patients. Pulmonary artery pressure of the group II
      patients was significantly higher than that of group I patients (27 +/- 4 mmHg vs
      22 +/- 1.6 mmHg, respectively p< 0.001). There were also statistically
      significant difference between group I and group II in respect to FEV1% (63 +/- 7
      vs 28 +/- 9 respectively p< 0.001), FEV1 L (1.84 +/- 0.46 vs 0.89 +/- 0.36
      respectively p< 0.001), FEV1/FVC (71 +/- 10 vs 53 +/- 11 respectively p< 0.001),
      FVC% (73 +/- 8 vs 47 +/- 10 respectively p< 0.001), and MMF% (38 +/- 13 vs 15 +/-
      6 respectively p< 0.001). Pulmonary artery pressure and diameter of right
      descending pulmonary artery on chest X-ray of the patients were negatively
      correlated with FEV1%, FEV1 L, FVC and MMF (p< 0.001 for all). We have shown
      pulmonary artery pressure of the patients with COPD was negatively correlated
      with the spirometric parameters such as FEV1%, FEV1 L, FVC and MMF. So FEV1 < 50%
      can be used as an indicator of increased pulmonary artery pressure in patients
      with COPD.

PMID- 15241701
TI  - [Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease].
AB  - Video-assisted thoracoscopic surgery (VATS) is a diagnostic method, used with
      increasing frequency in recent years, in the diagnosis of interstitial lung
      diseases. There are significant differences in the diagnosis of diseases which
      are diagnosed with clinical, biochemical and radiological investigation and with
      pathological evaluation of material obtained by VATS. In our study, five patients
      with different clinical and VATS guided pathological diagnosis, were analyzed.
      VATS was applied to four patients with clinical and radiological diagnosis of
      lymphangioleiomyomatosis, hypersensitivity pneumonitis and idiopathic pulmonary
      fibrosis (IPF) (two patients) at the beginning and to another patient with
      pulmonary tuberculosis (Tbc) who was ARB positive and no regression could be
      achieved with anti-Tbc treatment at the third month. Clinical and pathological
      diagnosis was different in all patients. In a 22 year old female, who was thought
      to be lymphangioleiomyomatosis, was pathologically diagnosed as histiocytosis-X;
      in a 55 year old female, who was thought to be hypersensitivity pneumonitis, was
      diagnosed as sarcoidosis; in a 58 year old male, who was thought to be IPF, was
      diagnosed as nonspecific interstitial pneumonia. Sixty-two year old patient with
      ARB positive pulmoner Tbc who had no clinical and radiological regression with
      three month anti-Tbc therapy, and 65 year old male patient who was thought to be
      IPF were diagnosed by VATS as bronchoalveolar carcinoma. In conclusion; VATS is
      one of the most important methods for definite diagnosis of interstitial lung
      diseases, in patients with interstitial involvement.

PMID- 15241702
TI  - [A case of chronic eosinophilic pneumonia with atypical clinical and radiological
      progress].
AB  - Eosinophilic lung disease is characterised by eosinophilic infiltration of lung
      tissue besides peripherical blood and bronchoalveolar lavage (BAL) fluid
      eosinophilia. A 48 year-old male who attended our clinics with cough and sputum
      lasting for 2-3 months, has been evaluated for micronodular interstitial
      infiltration bilaterally in all lung areas. Eosinophilia was detected in hemogram
      but BAL fluid was not diagnostic. Transbronchial lung parenchymal biopsy was
      compliant with chronic eosinophilic pneumonia. No special cause has been found
      after evaluation and the case was accepted to be idiopathic. Because of
      unfamiliar clinical, radiological and pathological findings, we decided to
      present this case.

PMID- 15241703
TI  - [A case of arteriovenous malformation seen as an endobronchial lesion].
AB  - Pulmonary arteriovenous malformation (PAVM) is an abnormal communication between
      pulmonary arteries and pulmonary veins, and congenital form is seen more
      prevalently. The classic radiological appearance is a round, well-circumscribed
      lesion. PAVM was observed in a 22-year-old male as an endobronchial lesion, and
      treated by wedge resection. Reviewing the literature, we identified only one case
      report that describes endobronchial view of PAVM.

PMID- 15241704
TI  - A case report of endobronchial semi-invasive aspergillosis.
AB  - Pulmonary aspergillosis may be classified under three main categories. These are
      invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and
      aspergilloma. Sometimes more than one form of the disease may be present at the
      same time. Semi-invasive aspergillosis is different from aspergilloma in that
      there is local invasion of the lung tissue. We have observed a previously healthy
      42 year old female with a solitary pulmonary nodule on her radiograms. A
      diagnosis of endobronchial semi-invasive aspergillosis was established in this
      patient. We aimed to present this case report with a review of the literature.

PMID- 15241705
TI  - [Tracheobronchopathia osteochondroplastica: a case report].
AB  - Tracheobronchopathia osteochondroplastica (TO) is a rare disorder with unknown
      aetiology. In this paper, a case with TO was presented. A 77 year-old-man was
      admitted with cough for 2 years. Chest X-ray showed interstitial changes.
      Computed tomography of thorax demonstrated calcific density lesion in the trachea
      and in the left and right main bronchi. Fiberoptic bronchoscopy revealed numerous
      white, hard, irregular nodules on the anterior and lateral walls of trachea and
      on main bronchi. Pathologic diagnosis of bronchoscopic biopsy was TO.

PMID- 15241706
TI  - [Tracheal bronchus which is characterized with persistent cough].
AB  - A 57-year-old man admitted to department of pulmonary medicine with a history of
      persistent cough. Computed tomography showed there was a right tracheal bronchus
      originated from 1/3 distal region of trachea. We reported this case because of
      the rarity of pulmonary anomaly.

PMID- 15241707
TI  - [Pulmonary involvement in collagen tissue diseases].
AB  - Collagen tissue diseases are multisystem and heterogeneous group disease mediated
      inflammatory disorders. The pulmonary manifestations is more common and all
      elements of the lung are involved. However, symptoms of the respiratory system
      may be masked by exercise limitation due to involvement of the musculoskeletal
      system. The involvement may be subclinical or determined fulminant and life
      threatening dimension. In this review, the pulmonary involvement of the more
      common collagen tissue diseases are reviewed.

PMID- 15241708
TI  - [The principles of mechanical ventilation in ARDS].
AB  - Acute respiratory distress syndrome (ARDS) is a real challenge for the pulmonary
      and critical care physicians. Although it is quite frequently encountered in
      intensive care clinics, its diagnosis and treatment bare many variations among
      the clinicians. Since ARDS is a fully dynamic process, there is no uniform
      application of mechanical ventilation (MV) being one of the inevitable components
      of ARDS management. This situation makes the clinicians very prone to make
      mistakes during setting and subsequent adjustments of mechanical ventilation
      parameters. In this review, we aimed to clarify the most common issues of
      discussion by presenting the principles of MV in ARDS with regard to some recent
      modifications.

PMID- 15241710
TI  - Effect of an acute bout of soccer heading on postural control and self-reported
      concussion symptoms.
AB  - Our purpose was to determine if an acute bout of heading soccer balls adversely
      affected postural control and self-reported symptoms of cerebral concussion.
      Thirty-one college-aged soccer players were randomly placed into either a kicking
      group or a heading group. Subjects either kicked or headed 18 soccer balls over
      the course of 40 minutes. Subjects had their postural control assessed while
      standing on a force plate and completed a concussion symptoms checklist on three
      separate occasions: prior to, immediately following, and 24 hours after kicking
      or heading. There were no significant differences between the heading and kicking
      groups on the postural control measures prior to, immediately following, and 24
      hours after kicking/heading. The heading group did, however, report significantly
      more concussion symptoms than the kicking group immediately after heading, but
      not 24 hours after heading. The number of previous concussions sustained by
      subjects did not influence the effects of heading. An acute bout of soccer
      heading appears to cause an increase in self-reported symptoms of cerebral
      concussion lasting less than 24 hours but no quantifiable deficits in postural
      control. Further research is needed to investigate the cumulative effects of
      soccer heading on postural control and other objective measures of brain
      function.

PMID- 15241711
TI  - The effect of mechanical loading on the MyHC synthesis rate and composition in
      rat plantaris muscle.
AB  - The aim of this study was to investigate the response of protein synthesis rate,
      particularly myosin heavy chain (MyHC) isoforms synthesis and the magnitude of
      its isoform transformation in fast-twitch plantaris muscle, to different modes of
      prolonged mechanical loading. Different protocols of mechanical loading were
      used: resistance training (RT), compensatory hypertrophy (CH) of m. plantaris
      after tenotomy of m. gastrocnemius and a combination of the two previous loadings
      (RT + CH). During the different modes of loading, plantaris muscle hypertrophy in
      RT group was approximately 10 %, CH approximately 40 % and CH + RT approximately
      44 %. MyHC I and IID isoform synthesis rate increased in all experimental groups,
      as well as their relative content. MyHC IIA relative content decreased during RT
      and RT + CH and increased during CH. MHC IIB isoform relative content decreased
      in all experimental groups, but compared with CH in CH + RT MyHC IIB isoform
      content increased in plantaris muscle. These results demonstrate that different
      modes of mechanical loading resulted in the selective up- and down-regulation of
      MyHC isoforms in fast-twitch skeletal muscle. The synthesis rate and relative
      content of the two fastest isoforms of MyHC IIB and IID are regulated to
      different directions during mechanical loading.

PMID- 15241712
TI  - Sustained swimming increases erythrocyte MCT1 during erythropoiesis and ability
      to regulate pH homeostasis in rat.
AB  - We investigated the effect of sustained swimming exercise on the increase in
      monocarboxylate transporter 1 (MCT1) concentration and its ability to regulate pH
      homeostasis in rat erythrocytes. Male Sprague-Dawley rats aged 9 weeks were
      divided into sedentary and swimming groups for both 1- and 3-week experiments.
      The exercise group swam for 30 - 60 min/day, 5 days/week. Before and 1 and 3
      weeks after initiation of the exercise, blood was collected for lactate
      concentration measurement during pre-exercise rest and post-exercise recovery
      periods. On the last day of each experiment, venous blood and erythroid cells in
      bone marrow were collected to assay the capacity for erythropoiesis and MCT1
      concentration. In the swimming group at 0 weeks (p < 0.05), 1 week (p < 0.01) and
      3 weeks (p < 0.001), the blood lactate concentration post-exercise was
      significantly higher than at rest. The ratio of young erythrocytes to total
      erythrocytes was significantly higher in the 3-week swimming group than in the
      sedentary group (p < 0.05). The MCT1 concentration in erythrocytes was higher in
      the 3-week swimming group than in the sedentary group (18 %, p < 0.05), which was
      found in young erythrocytes (22 %, p < 0.05) when total erythrocytes were
      separated into young and old fractions. The MCT1 concentration in erythroid cells
      was higher in both the 1-week and 3-week swimming groups than in either of the
      sedentary groups (27 and 28 %, respectively, p < 0.05). The pH recovery of
      erythrocyte suspensions at 10, 15 and 20 seconds after addition of lactate to the
      suspension medium was significantly faster in the 3-week swimming group than in
      the sedentary group (p < 0.001). These findings suggest that erythrocyte MCT1 is
      increased during erythropoiesis in bone marrow and that the increase of the
      transporter facilitates, at least partly, lactate/proton co-transport due to
      sustained swimming exercise in rats.

PMID- 15241713
TI  - Physical activity and genetic influences in risk factors and aging: a study on
      twins.
AB  - The association between physical activity and a decreased risk of age-correlated
      diseases appears to be well established. Nevertheless, the relation between past
      life style and current health in the elderly is likely to be affected by
      interactions of environmental and genetic factors in mediating the effects of
      exercise on disease prevention. As a contribution to this general issue, a
      retrospective twin study was undertaken so as to take advantage of the classical
      twin method in assessing genetic influences on health status in the elderly. A
      more specific aim was to possibly identify and compare genetically identical
      elderly twins with substantial differences in previous exposure to physical
      activity, but otherwise similar life style factors and events, thereby allowing
      the application of the co-twin case-control method, a powerful experimental
      approach in which even a few cases may prove significant. The study involved the
      assessment of general health status (based on structured interviews, clinical
      examination and several functional and laboratory analyses) and life style in 27
      male twin pairs, aged 71.0 +/- 2.6 and classified (through DNA analysis) as 13
      monozygotic and 14 dizygotic pairs. Past and present physical activity were
      evaluated through the Modified Baecke Questionnaire for Older Adults. In general,
      higher intrapair correlations in monozygotic than dizygotic pairs for almost all
      clinical variables were found, thereby confirming the relevance of genetic
      effects. More specifically, five monozygotic pairs discordant for past physical
      activity were found: contrary to expectations and, notwithstanding this major
      difference, they did not appear to be less similar than other pairs with respect
      to general health status. More data are clearly needed, and the implications of
      these findings, if confirmed, may leave room for complex interpretations.
      Tentatively, however, one might be led to conclude that whatever protective role
      physical activity and other life style variables clearly play in general health,
      this may in the end be unable to offset strong genetic dispositions, particularly
      so when it comes to major risk factors, which, after all, is perhaps only
      reasonable.

PMID- 15241714
TI  - Effect of glycogen depletion on the oxygen uptake slow component in humans.
AB  - Previous studies have indicated that the (.-)VO(2) slow component is related to
      the recruitment of type II muscle fibres. We therefore hypothesised that an
      exercise and dietary regimen designed to deplete type I muscle fibres of glycogen
      would result in a greater contribution of type II muscle fibres to the exercise
      power output and therefore a larger amplitude of the (.-)VO(2) slow component.
      Eight male subjects took part in this study. On day 1, the subjects reported to
      the laboratory at 8 a.m., and completed a 9 min constant-load cycling test at a
      work rate equivalent to 85 % (.-)VO(2) peak. On day 2 at 12 p.m., the subjects
      were fed a 4200 kJ meal (60 % protein, 40 % fat); at 6 p.m. they completed a 2 h
      cycling test at 60 % (.-)VO(2) peak. On day 3 at 8 a.m., the subjects performed
      an exercise test identical to that of day 1. Metabolic and respiratory
      measurements indicated that our experimental design was effective in reducing the
      muscle glycogen content. (.-)VO(2) was significantly higher (by approximately 140
      ml x min (-1)) throughout exercise following glycogen depletion but no
      appreciable changes in (.-)VO(2) kinetics were found: neither the time constant
      of the primary response (from 35.4 +/- 2.5 to 33.2 +/- 4.4 s) nor the amplitude
      of the slow component (from 404 +/- 95 to 376 +/- 81 ml x min (-1)) was
      significantly altered. Therefore, we suggest that the increased (.-)VO(2)
      throughout exercise and the unaltered (.-)VO(2) slow component following glycogen
      depletion might be explained by a shift towards a greater reliance on fat
      metabolism in type I muscle fibres with no appreciable change in fibre type
      recruitment patterns.

PMID- 15241715
TI  - The relationship between power and time to fatigue in cycle ergometer exercise.
AB  - The purpose of this study was to evaluate three critical power (P (critical))
      models. Ten university students performed tests that elicited fatigue in > 2 min
      to approximately 10 min. Power and time data were fit to a 2-parameter hyperbolic
      model, a 3-parameter hyperbolic model, and a 3-parameter exponential model.
      Models described the power-time relationship well (R (2) > or = 0.995). However,
      P (critical) (209 +/- 51 W; SEE: 20 +/- 47 W) and the time constant (198 +/- 87
      s; SEE: 103 +/- 246 W) from the exponential model have no obvious meaning. The 2
      parameter model produced P (critical) (187 +/- 38 W) and anaerobic work capacity
      (20.4 +/- 9.0 kJ) that have known physiological meaning, with excellent
      confidence (SEE: 2 +/- 2 W and 1.0 +/- 1.0 kJ, respectively). Addition of a
      maximal power parameter to the 2-parameter model did not improve description of
      the relationship, and the third parameter was superfluous. The 2-parameter model
      was preferred because, for the range of exercise durations used in this study, it
      describes the power-relationship adequately and in a most parsimonious fashion.

PMID- 15241716
TI  - The reproducibility of perceptually regulated exercise responses during short
      term cycle ergometry.
AB  - The purpose of this study was to assess the reproducibility over four trials of
      perceptually regulated exercise intensity during short-term cycle ergometry.
      Recent research has suggested that an improvement in the reproducibility (better
      agreement) of the exercise output would be observed with a repeated practice
      using regulatory tools such as Borg's 6 - 20 rating of perceived exertion (RPE)
      scale. Eighteen healthy active volunteers (nine males, mean age (+/- SD) 24.7 +/-
      3.4 yr, and nine females 27.6 +/- 5.4 yr) completed four identical intermittent
      effort production trials on a cycle ergometer over a period of two - three weeks,
      with all trials being between three and five days apart. After warm-up, the
      volunteers were asked to produce four x three-minute bouts of exercise at RPE
      levels: 13, 15, 9, and 17 (in this order). Power output (W), percentage maximum
      heart rate reserve (%MHRR), and oxygen consumption (VO(2); ml x kg(-1) x min(-1))
      were recorded in the final minute of each bout. Analysis revealed that the 95 %
      limits of agreement (LoA) between repeated trials did not decrease for the
      objective markers of exercise intensity, remaining wide throughout. In the worst
      case comparisons the LoA represented changes (expressed as a proportion of the
      mean of two trials) of up to 58.3 % in power output (T2 vs. T3 at RPE 9), 65.5 %
      in % MHRR (T1 vs. T2 at RPE 13) and 36.5 % in VO(2) (T3 vs. T4 at RPE 17). These
      findings question the use of ratings of perceived exertion to regulate exercise
      effort. That the reproducibility of effort is also not seen to improve with
      practice raises doubts about the validity of using the RPE scale to provide
      training intensities for this type of exercise.

PMID- 15241717
TI  - Peak power output predicts rowing ergometer performance in elite male rowers.
AB  - The aim of the present study was to test the hypothesis that peak power output
      (Ppeak) sustained during maximal incremental testing would be an overall index of
      rowing ergometer performance over 2000 m (P2000), and to study the influence of
      selected physiological variables on Ppeak. A group of 54 highly trained rowers
      (31 heavyweight [HW] and 23 lightweight [LW] rowers) was studied. Body mass,
      maximal oxygen uptake ((.-)VO(2max)), oxygen consumption corresponding to a blood
      lactate of 4 mmol. l (-1) expressed in percentage of (.-)VO(2max) (V.O (2)La4 %),
      and rowing gross efficiency (RGE) were also determined during the incremental
      test. In the whole group Ppeak was the best predictor of P2000 (r = 0.92, p <
      0.0001). Body mass (r = 0.65, p < 0.0001), V.O (2max) (r = 0.84, p < 0.0001), (.
      )VO 2)La4 % (r = 0.49, p < 0.0001) and RGE (r = 0.35, p < 0.01) were
      significantly correlated with P2000 as well. To take the influence of body mass
      into account, (.-)VO(2max) was related to kg (0.57). Ppeak was significantly
      related to body mass (r = 0.56, p < 0.0001), (.-)VO(2max) x kg (-0.57) (r = 0.63,
      p < 0.0001), (.-)VO(2)La4 % (r = 0.45, p < 0.001) and RGE (r = 0.34, p < 0.05).
      Multiple regression analysis indicated that the above parameters taken together
      explained 82.8 % of Ppeak variation in the whole group. It was also demonstrated
      that Ppeak was the best predictor of P2000 when LW and HW groups were considered
      separately. It was concluded that, by integrating the main physiological factors
      of performance, Ppeak is an overall index of physiological rowing capacity and
      rowing efficiency in heterogeneous as well as in homogeneous groups. It presents
      the further advantage of being easily measured in the field.

PMID- 15241718
TI  - No differences in cycling efficiency between world-class and recreational
      cyclists.
AB  - The aim of this experiment was to compare the efficiency of elite cyclists with
      that of trained and recreational cyclists. Male subjects (N = 69) performed an
      incremental exercise test to exhaustion on an electrically braked cycle
      ergometer. Cadence was maintained between 80 - 90 rpm. Energy expenditure was
      estimated from measures of oxygen uptake (VO (2)) and carbon dioxide production
      (VCO(2)) using stoichiometric equations. Subjects (age 26 +/- 7 yr, body mass
      74.0 +/- 6.3 kg, Wpeak 359 +/- 40 W and VO(2)peak 62.3 +/- 7.0 mL/kg/min) were
      divided into 3 groups on the basis of their VO (2)peak (< 60.0 (Low, N = 26), 60 
      70 (Med, N = 27) and > 70 (High, N = 16) mL/kg/min). All data are mean +/- SE.
      Despite the wide range in aerobic capacities gross efficiency (GE) at 165 W (GE
      (165)), GE at the same relative intensity (GE (final)), delta efficiency (DE) and
      economy (EC) were similar between all groups. Mean GE (165) was 18.6 +/- 0.3 %,
      18.8 +/- 0.4 % and 17.9 +/- 0.3 % while mean DE was 22.4 +/- 0.4 %, 21.6 +/- 0.4
      % and 21.2 +/- 0.5 % (for Low, Medium and High, respectively). There was no
      correlation between GE (165), GE (final), DE or EC and VO(2)peak. Based on these
      data, we conclude that there are no differences in efficiency and economy between
      elite cyclists and recreational level cyclists.

PMID- 15241719
TI  - Left ventricular morphology and function in female athletes: a meta-analysis.
AB  - The purpose of the present study was to examine the impact of physical training
      upon cardiac structure and function, and identify physiologic upper limits in
      female athletes. Meta-analytical techniques were applied to 13 published
      echocardiographic studies examining cardiac structure and function in female
      athletes. The study group included 890 athletes and 333 controls. For comparison
      of sporting discipline, studies were partitioned into 3 categories (endurance,
      strength/sprint, team). Significant (p < 0.05) effect sizes were observed for all
      structural measures between athletes and controls. Significant effect size
      differences existed between sporting groups for LVIDd and LVM only, with
      endurance and team game athletes demonstrating the largest effect sizes compared
      to strength trained athletes. No significant effect of training was observed for
      left ventricular diastolic or systolic function, with the exception of stroke
      volume where a significant effect size difference was observed between athletes
      and controls with no observed difference between sporting groups. Maximum
      reported upper limits for LV wall thickness and LVIDd in female athletes were 12
      mm and 66 mm respectively. Chronic exercise training results in cardiac
      enlargement in female athletes. The nature of physiologic adaptation is similar
      to that observed in male athletes. LV wall thickness values greater than 12 mm in
      female athletes should be viewed with caution and indicate a more comprehensive
      evaluation to establish a physiological or pathological basis for the observed
      left ventricular enlargement.

PMID- 15241720
TI  - Bone mineral density in Hispanic women: role of aerobic capacity, fat-free mass,
      and adiposity.
AB  - Understanding the etiology of factors influencing bone mineral density (BMD) in
      Hispanic women for the prevention of osteoporosis was the aim of this
      investigation. Whole body BMD (WBBMD) of 39 Hispanic, premenopausal women aged 22
      - 51 years was measured using dual-energy X-ray absorptiometry (DXA). Maximal
      aerobic capacity ((.-)VO(2max)) was determined by treadmill ergometry with direct
      measurement of oxygen consumption. Fat-free mass (FFM) and fat mass were
      estimated from two independent techniques, DXA and bioelectrical impedance
      analysis (BIA). A questionnaire was administered to determine weekly physical
      activity, age of menarche, oral contraceptive (OC) use, parity, and lactation.
      Factors with significant correlation to WBBMD were weight ( r = 0.74), body mass
      index ( r = 0.66), fat mass ( r = 0.68 - 0.69), FFM ( r = 0.55 - 0.65), percent
      fat ( r = 0.43 - 0.55), sagittal diameter ( r = 0.58), waist circumference ( r =
      0.53), hip circumference ( r = 0.66) and weekly activity ( r = 0.40). Stepwise
      multiple linear regression revealed that 73 % of the variance in WBBMD is
      attributed to fat mass (55 %), FFM (10 %), and (.-)VO(2max) (8 %). When BIA was
      used instead of DXA in the regression, (.-)VO(2max) was no longer an independent
      predictor of WBBMD. Fat mass and FFM accounted for 43 % and 20 % of the variance
      in WBBMD, respectively, explaining a total of 63 % of the variance. The addition
      of age, age of menarche, weekly physical activity, OC use, parity, and lactation
      did not make significant contributions to the variance. The findings of this
      study suggest that fat mass is a stronger predictor of bone mineral density than
      fat-free mass to BMD; aerobic capacity is another important predictor of BMD in
      Hispanic premenopausal women.

PMID- 15241721
TI  - Effects of eccentric phase velocity of plyometric training on the vertical jump.
AB  - The aim of this study was to compare the effects of plyometric training performed
      with rapid or slow stretch contraction on jump performance and muscle properties.
      Thirty males between the ages of 19 and 22 volunteered for the 8-week experiment.
      Subjects were divided into the following three groups: training group 1 (TG1),
      training group 2 (TG2), and control group (CG). Each of the two experimental
      groups underwent a unique training regimen. For the first group (TG1, n = 12):
      from a standing position the subject flexed his knees to a 90 degrees angle with
      velocity standardized and controlled at 0.4 m/s and immediately performed a leg
      extension as quickly as possible. For the second group (TG2, n = 12): from a
      standing position, the subject flexed his knees to a 90 degrees angle with
      velocity standardized at 0.2 m/s and then performed a leg extension as quickly as
      possible. Each exercise consisted of six sets of ten repetitions with a barbell
      on the shoulders at 70 % of the maximal isometric force (1 RM). The 70 % load was
      modified at two-week intervals by evaluating a new 1 RM. Exercises were performed
      four times a week over the eight-week period. The third group (CG, n = 6), served
      as the control group. Maximal isometric force (MVC), maximal concentric force,
      squat jump (SJ) and counter movement jump (CMJ) exercises were performed before
      and after the training program. Subjects were filmed (100 Hz) and each jump was
      divided into three phases: eccentric phase (ECC), transition phase (TR) and
      concentric phase (CON). Surface EMG was used to determine the changes in the
      electromyographic (EMG) activity before and after the training program. There was
      an increase in leg extension force, velocity and electrical activity for SJ and
      CMJ for the two training groups (p < 0.05). However, TG1 showed a significant
      advantage in CMJ performance as well as a significant decrease in TR compared to
      the TG2 (p < 0.05). The results of this study show that when plyometric training
      is performed with rapid stretch contraction the CMJ jump height increases and the
      TR decreases.

PMID- 15241723
TI  - Pregnancy-associated corticosteroid-binding globulin: high resolution separation
      of glycan isoforms.
AB  - Corticosteroid-binding globulin (CBG) is a glycoprotein that functions as a
      specific carrier of cortisol in the circulation. CBG contains six sites for N
      glycosylation with, on average, five sites occupied by a mixture of biantennary
      and triantennary oligosaccharides with variable additional terminal sialic acid
      residues leading to glycoforms with significant heterogeneity in mass and
      isoelectric points. During pregnancy, a form of CBG possessing only triantennary
      oligosaccharides comprising approximately 10 % of total CBG appears specifically.
      We describe the first application of two-dimensional gel electrophoresis to the
      separation of human CBG glycoforms. This technique resolved a greater degree of
      charge heterogeneity than previous studies, and allowed simultaneous
      visualization of changes to the size and isoelectric points of CBG during
      pregnancy. Profiles of CBG glycoforms during pregnancy showed a general increase
      in size followed by a shift to lower pI in a large proportion of the
      glycoprotein. This may result from the enhancement of triantennary glycosylation,
      with the extent of incorporation of sialic acid increasing with the number of
      available sites for its addition. The pregnancy-specific CBG previously defined
      probably represents a subset of the acidic and high molecular weight glycoforms
      we have resolved by two-dimensional electrophoresis and now describe as pregnancy
      associated CBG.

PMID- 15241724
TI  - Glucocorticoids and melanocortins in the regulation of body weight in humans.
AB  - The last decade witnessed a dramatic increase in knowledge concerning regulation
      of body weight and obesity. According to recent concepts constancy of body weight
      is a side product of regulatory events which ensure constant glucose fluxes to
      the brain. Within these control systems glucocorticoids and melanocortins play a
      fundamental role at several sites. The melanocortin neurons in the arcuate
      nucleus are important mediators of the feedback effects of leptin and insulin.
      Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial
      as they define the balance between glucose allocation processes and food intake.
      Thereby, the hippocampal structures determine the setpoint for bodyweight
      regulation. Novel approaches to treatment of obesity must aim at manipulating
      these brain structures.

PMID- 15241725
TI  - Hypothalamic regulation of adiposity: the role of 11beta-hydroxysteroid
      dehydrogenase type 1.
AB  - Following extensive suprasellar operations for excision of hypothalamic tumors,
      some patients develop morbid obesity despite receiving replacement doses of
      glucocorticoids. Urine analysis of cortisol and cortisone metabolites show that
      11-OH/11-oxo ratios are significantly higher in patients with hypothalamic
      obesity, indicating enhanced 11beta-HSD1 activity. This correlates with the
      visceral-to-subcutaneous fat ratio. The consequence of increased 11beta-HSD1
      activity and a shift of the steroid inter-conversion towards cortisol may
      contribute to the effects of the latter in adipose tissue. The message from the
      hypothalamus to adipocyte 11beta-HSD-1 involves hormones, the sympathetic nervous
      system and cytokines. CRH and ACTH downregulate 11beta-HSD-1 activity and induce
      lipolysis. Tumor necrosis factor-alpha and interleukin-1beta upregulate 11beta
      HSD-1 expression and activity, while enhancing lipolysis. The sympathetic nervous
      system exerts its effects through beta-adrenergic upregulation and alpha
      adrenergic downregulation of 11beta-HSD-1 activity. Inhibition of 11beta-HSD-1
      suppresses preadipocyte differentiation into mature adipocytes, and may provide a
      therapeutic tool.

PMID- 15241726
TI  - Orexins (hypocretins) and adrenal function.
AB  - The recently discovered neuropeptides orexin A and B regulate feeding behavior,
      neuroendocrine and autonomic functions, and sleep-wakefulness by central
      mechanisms. The expression of orexins and orexin receptors in various peripheral
      organs and the presence of orexin A in blood indicate the existence of a
      peripheral orexin system. In rat and human adrenal glands, both OX (1) and OX (2)
      receptor subtypes have been described with a predominant expression of OX (2)
      receptors in the adrenal cortex. In male rats, adrenocortical OX (2) receptors
      are much higher expressed than in female rats. Various experimental data
      demonstrate a stimulatory effect of orexins on the secretion of adrenocortical
      steroids, mainly on glucocorticoids. Some results also suggest the regulation of
      catecholamine synthesis and release by orexins. Whether the gender-dependent
      expression of adrenocortical OX (2) receptors has functional correlates awaits
      future clarification. As plasma orexin appears to rise during hunger and
      hypoglycemia, orexins may link adrenal functions with energy homeostasis.

PMID- 15241727
TI  - Mechanisms of obesity-related hypertension.
AB  - Obesity has become an epidemic problem in western societies, contributing to
      metabolic diseases, hypertension and cardiovascular disease. Although the
      importance of obesity as a cause of hypertension is well established, the
      molecular basis of the relationship between obesity and increased blood pressure
      remains poorly understood. This brief review examines the association between
      obesity and hypertension along with the mechanisms proposed to explain this
      association, while presenting evidence of a direct causal effect of adipose
      tissue in the development of hypertension through the involvement of the adrenal
      cortex.

PMID- 15241729
TI  - Genetic dissection of corticosteroid receptor function in mice.
AB  - Functional genomic technologies, including artificial chromosome-based
      transgenesis and conditional gene targeting, allowed us to generate mouse models
      harboring genes with loss-of-function mutations, gain-of-function mutations,
      spatially and/or temporally restricted mutations, tissue-specific mutations, and
      function-selective mutations. This kind of "allelic series" for corticosteroid
      receptors in mouse models provides a very useful resource for the molecular
      understanding of corticosteroid function in vivo. These models will also support
      the identification of steroid receptor target genes in order to define a steroid
      signaling cascade in molecular terms. They provide opportunities for the
      identification of compounds that regulate steroid receptors in a tissue-specific
      and function-selective manner. For example, selective glucocorticoid receptor
      modulators preventing receptor dimerization and DNA binding can be expected to
      reduce osteoporotic and/or diabetogenic side effects, but to display partial or
      full anti-inflammatory potential. Thus, these mouse models will help to evaluate
      distinct steroid receptor functions for therapeutic intervention.

PMID- 15241728
TI  - The role of progesterone metabolism and androgen synthesis in renal blood
      pressure regulation.
AB  - 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in
      converting hormonally active cortisol into inactive cortisone, conferring
      specificity onto the human mineralocorticoid receptor (MR). Progesterone binds
      with even higher affinity to the MR, but acts as an MR antagonist. How
      aldosterone is able to keep its function as predominant MR ligand in clinical
      situations with high progesterone concentrations, such as pregnancy, is not
      clear. We have shown in vitro that the human kidney possesses an effective enzyme
      system that metabolizes progesterone to inactive metabolites in a process similar
      to the inactivation of cortisol by 11beta-HSD2. In studies on patients with
      adrenal insufficiency, we have shown that the in vivo anti-mineralocorticoid
      activity of progesterone is diminished by inactivating metabolism of
      progesterone, local formation of the deoxycorticosterone mineralocorticoid from
      progesterone, and inhibition of 11beta-HSD2 by progesterone and its metabolites
      resulting in decreased inactivation of cortisol and hence increased MR binding by
      cortisol. The enzymes involved in progesterone metabolism are also responsible
      for the capability of the human kidney to convert pregnenolone to DHEA and
      androstenedione leading to the formation of active androgens, testosterone and
      5alpha-DH-testosterone. Locally produced androgens might be responsible for the
      observed difference in blood pressure between men and women and higher
      susceptibility to hypertension in men.

PMID- 15241730
TI  - Role of the inhibin/activin system and luteinizing hormone in adrenocortical
      tumorigenesis.
AB  - Adrenal masses are one of the most common endocrine tumors diagnosed. Although
      most adrenal tumors are inactive adenomas, a considerable proportion is
      associated with hormonal hyperfunction and/or malignancy. The adrenocortical
      carcinoma (ACC) is a rare but highly malignant tumor. Most ACCs in adults are
      diagnosed in an advanced tumor stage limiting therapeutic options. Accordingly,
      despite some progress in diagnostic and therapeutic approaches, the overall
      survival rate of patients with ACC remains poor. However, the prerequisite for
      the development of new diagnostic tools and therapeutic options in the management
      of patients with ACC is the elucidation of the molecular pathogenesis of adrenal
      tumorigenesis. Although our understanding of adrenal tumor biology has increased
      substantially over the last decades, the regulation of many molecular pathways
      involved in adrenocortical growth and differentiation awaits further elucidation.
      Luteinizing hormone (LH) and activin have only recently emerged as hormones
      likely to play opposite roles in adrenocortical hormone secretion and cellular
      proliferation. Recent evidence from studies on human surgical tumor sample
      expression and detailed characterization of murine adrenal tumor models suggests
      stimulatory effects of LH on adrenocortical growth and function. On the contrary,
      activin, which plays a critical role as a paracrine and autocrine factor
      regulating cellular growth and differentiation, has been demonstrated to induce
      apoptosis and suppress proliferation in the human and murine adrenal cortex. In
      this review, we will summarize molecular and functional aspects of adrenal
      tumorigenesis and highlight some prospects for future clinical applications.

PMID- 15241731
TI  - Role of the insulin-like growth factor system in adrenocortical growth control
      and carcinogenesis.
AB  - Clinically silent adrenocortical adenomas are the most frequent abnormalities in
      the adrenal gland. In contrast, adrenocortical carcinoma is a rare tumor with an
      extremely poor prognosis. The factors responsible for the frequent occurrence of
      benign adrenocortical tumors on one hand and the rare malignant transformation on
      the other are not known. Several genetic alterations such as loss of imprinting
      or loss of heterozygosity of the 11p15 gene locus causing a strong IGF-II
      overexpression have been demonstrated in the majority of adrenocortical
      carcinomas. In addition to IGF-II overexpression, increased levels of the IGF-I
      receptor and IGFBP-2 have been found in advanced human adrenocortical carcinomas,
      suggesting an important role for the IGF-system in adrenocortical carcinogenesis.
      IGFs are potent mitogens regulating growth and apoptosis through interaction with
      the IGF-I-receptor, and overexpression of the human IGF-I-receptor promotes
      ligand-dependent neoplastic transformation in a variety of different cell
      systems. It is evident, therefore, that high levels of IGF-II in combination with
      overexpression of the IGF-I-receptor can provide a significant growth advantage
      for adrenocortical carcinoma cells and thus contribute to the highly malignant
      phenotype of this rare type of cancer. Additionally, it has been shown that
      overexpression of IGFBP-2 can promote malignant transformation of Y1 mouse
      adrenocortical tumor cells through unknown IGF-independent mechanisms. As one
      possible mechanism, we have recently found altered expression of catalase in
      IGFBP-2-overexpressing tumor cells, thus implicating IGFBP-2 in influencing
      intracellular peroxide levels. However, since transgenic mice with IGF-II or
      IGFBP-2 overexpression in the adrenal gland do not show an increased frequency of
      adrenal tumors, IGF-II or IGFBP-2 may act as progression factors but not as
      initiation factors in adrenocortical tumorigenesis.

PMID- 15241732
TI  - The role of the ACTH receptor in adrenal tumors: identification of a novel
      microsatellite marker.
AB  - In vitro, the growth inhibiting effect of ACTH on adrenocortical cells is well
      documented, even though there are reports of opposite effects under defined cell
      culture conditions. In vivo, activation of the ACTH receptor (ACTHR) has a
      trophic effect on the adrenal cortex, while the effects on proliferation are
      still under discussion, especially since other POMC derived peptides have been
      characterized. However, ACTH is thought to act as a differentiation factor with
      inhibiting effects on tumor growth. In undifferentiated adrenocortical
      carcinomas, ACTHR expression is frequently lost, which is associated with
      extensive tumor growth. We describe a new microsatellite marker within the intron
      of the ACTHR gene termed ACTHRint1. In a series of 114 patients with various
      adrenal and non-adrenal tumors, the rate of heterozygosity was 100 %. Only one
      out of 57 patients with adrenocortical adenoma showed LOH at the ACTHR locus,
      whereas 4 of 10 carcinomas had loss of one allele. Patients suffering from tumors
      with LOH showed a more aggressive disease course and had earlier recurrences with
      poor prognosis. These data confirm earlier findings that adrenocortical
      carcinomas frequently show loss of ACTHR expression, which is associated with a
      more aggressive tumor growth. However, whether the ACTHR is directly involved in
      tumor growth or acts a marker of differentiation that is lost in more advanced
      tumor stages is still not clear.

PMID- 15241733
TI  - Cytotoxic T-cell response against steroidogenic acute regulatory protein using
      DNA vaccination followed by vaccinia virus infection in a mouse adrenal carcinoma
      model.
AB  - Adrenocortical carcinoma (ACC) is still one of the most devastating human tumors
      with a five year survival as low as 20 %. In a previous study, we showed that DNA
      vaccination followed by vaccinia virus was able to break immune tolerance against
      murine steroidogenic acute regulatory (mStAR). Prophylactic vaccination in
      syngenic mice resulted in protective immunity against Sp2-0 tumor cells
      expressing mStAR. However, approximately a third of the animals developed tumors
      despite vaccination. This prompted us to investigate whether vaccination failure
      is responsible for this phenomenon. BALB/cBALB/c mice (in groups of 6 - 9
      animals) were vaccinated intramuscularly by injection of cDNA expression vectors
      encoding mStAR three times at weekly intervals. This was followed by a
      recombinant vaccinia virus (rVV-mStAR) infection to boost immune response. Ten
      days after the last vaccination, Sp2-mStAR or parental Sp2-0 cells (as controls)
      were injected s. c. Tumor development was monitored by daily palpation.
      Approximately two weeks later, the animals were sacrificed and the spleens
      removed. After restimulation with the cell lines expressing mStAR, the
      splenocytes were tested for presence of mStAR self-reactive cytotoxic T
      lymphocytes using ELISPOT analysis. With this approach, we were able to show that
      those animals protected from tumor growth had a specific T-cell response against
      StAR whereas mice without a specific T-cell response developed Sp2-mStAR tumors.
      Our data demonstrate that vaccination failure, probably due to the low
      antigenicity of mStAR, is responsible for tumor growth in our model system.

PMID- 15241734
TI  - Gas chromatography-mass spectrometry profiling of steroids in times of molecular
      biology.
AB  - This review's aim is to outline the potential of gas chromatography-mass
      spectrometry profiling of steroids in the diagnosis of endogenous human steroid
      disorders. Mass spectrometry currently provides the highest specificity in
      clinical steroid analysis. The non-invasive and non-selective GC-MS urinary
      steroid profiling technique enables diagnosis of almost any adrenal enzyme
      defects in steroid biosynthesis. While enzymatic defects can be diagnosed from
      spot urine samples in most cases, analysis of 24-hr urinary samples permits
      determination of hormonal excretion rates or enables diagnostic or therapeutic
      monitoring of steroid related diseases. Profiling plasma steroids by isotope
      dilution/GC-MS is particularly suitable where only minimal plasma samples are
      available and/or the highest specificity is required; therefore, GC-MS steroid
      profiling presents a complementary analytical technique whenever highest
      specificity is required. Clinical GC-MS profiling of steroids is also highly
      recommended as a reasonable initial diagnostic approach--especially in unclear
      situations--avoiding uncritical and expensive attempts at molecular diagnostic
      testing.

PMID- 15241736
TI  - Current views on imaging of adrenal tumors.
AB  - Anatomical imaging modalities (such as computed tomography [CT] or magnetic
      resonance imaging [MRI]) and functional imaging modalities (that is, nuclear
      medicine) are used in the evaluation of adrenal glands. The use of CT
      (unenhanced, followed by contrast-enhanced) evaluation is the cornerstone of
      imaging of adrenal tumors. Attenuation values of less than 10 Hounsfield units at
      unenhanced CT are practically diagnostic for adenomas, while attenuation values
      of greater than 10 HU are not diagnostic of metastatic disease since non
      metastatic disease is also a possibility. When lesions cannot be characterized
      adequately with CT, MRI evaluation (with T1 and T2-weighted sequences and
      chemical shift and fat-suppression refinements) is sought. Functional nuclear
      medicine imaging can be of utility in the evaluation of adrenal masses, more
      particularly for lesions not adequately characterized with CT and MRI. Nuclear
      medicine techniques are based on physiological and pathophysiological processes
      (cellular metabolism, tissue perfusion and local synthesis, uptake, storage of
      hormones and their receptors). Functional imaging aids initial preoperative
      staging, diagnostic evaluation of suspicious lesions, identification of
      metastatic or recurrent tumors, refining prognosis, and deciding on and
      predicting responses to therapy. [ (131)I]-6-iodomethyl norcholesterol
      scintigraphy can differentiate adenomas from carcinomas. Pheochromocytomas appear
      as areas of abnormal/increased [ (131)I]- and [ (123)I]-meta-iodobenzylguanidine
      uptake. Our experience has shown that [ (18)F]-fluorodopamine is an excellent
      agent for localizing adrenal and extra-adrenal pheochromocytomas.

PMID- 15241735
TI  - Pharmacodynamics and pharmacokinetics of synthetic mineralocorticoids and
      glucocorticoids: receptor transactivation and prereceptor metabolism by 11beta
      hydroxysteroid-dehydrogenases.
AB  - Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is
      determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases
      (HSDs) and receptor transactivation. We characterized these parameters for
      steroids often used in clinical practice. HSD activity was examined in human
      liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected
      with both enzymes. GC and MC transcriptional activity was tested by luciferase
      assay in CV-1 cells transfected with human GC or MC receptor expression vectors.
      The 11-hydroxy-group is necessary for GC and MC receptor transactivation. As HSD2
      oxidizes 11-hydroxysteroids to inactive 11-dehydrosteroids, GC and MC activity in
      HSD2-expressing tissues (kidney, colon) is regulated by this enzyme. As 9alpha
      fluorination (such as in 9alpha-fluorocortisol) decreases oxidation by HSD2 and
      increases both GC and MC receptor transactivation, this modification leads to
      optimal, but non-selective transactivation of both receptors. Increased GC
      receptor and decreased MC receptor transactivation leading to more selective GC
      activity is reached using the following substituents: 16beta-methyl (in
      betamethasone), 16alpha-methyl (in dexamethasone) and triangle up 1-dehydro
      configuration (in prednisolone). Whereas the modifications in position 16
      decrease oxidation by HSD2, the triangle up 1-dehydro-configuration increases
      HSD2-activity leading to an enhanced inactivation of prednisolone compared to all
      other steroids. 9alpha-fluorocortisol, the most frequently used substance for MC
      substitution, seems to be the best choice of available steroids for this purpose.
      Whereas GC selectivity can be improved by hydrophobic substituents in position 16
      and the triangle up 1-dehydro-configuration, maximal GC activity needs additional
      fluorination in position 9alpha (such as in dexamethasone). For GC therapy
      directed to HSD2-expressing organs, widely used prednisolone does not seem to be
      the optimal recommendation.

PMID- 15241738
TI  - Cardiovascular care in end-stage renal disease.
AB  - Cardiovascular disease (CVD) accounts for the majority of morbidity and mortality
      in patients with end-stage renal disease (ESRD). Chronic kidney disease, and ESRD
      as its most severe form, are now acknowledged to be independent risk factors for
      CVD. The spectrum of CVD includes accelerated atherosclerosis, myocardial disease
      and heart failure, cardiac arrhythmias, and valvular heart disease. In addition,
      CKD and ESRD are independent and powerful factors that complicate cardiovascular
      procedures and have been directly linked to increased mortality. This issue of
      Advances in Chronic Kidney Disease will explore the spectrum of risk and the
      opportunities to improve care in ESRD in outpatient management, during dialysis,
      after kidney transplantation, and in coronary revascularization.

PMID- 15241739
TI  - The evaluation of underlying cardiovascular disease among patients with end-stage
      renal disease.
AB  - Although coronary artery disease (CAD) is highly prevalent among patients with
      chronic kidney disease (CKD), interventions proven to reduce cardiovascular
      disease (CVD) mortality are underutilized in this population of patients. Given
      the burden of CVD in this population, knowledge of specific diagnostic tests for
      detection and evaluation of CAD in patients with end-stage renal disease (ESRD)
      and their correlation with outcomes is imperative for the practicing
      nephrologist. Studies that examine the use of exercise electrocardiography
      testing, pharmacologic stress imaging, single-photon emission computed
      tomographic myocardial perfusion imaging, electron beam computed tomography, and
      dobutamine stress echocardiography among patients with ESRD are detailed with
      recommendations for the noninvasive evaluation of CAD in this population.

PMID- 15241740
TI  - Coronary revascularization in patients with coronary artery disease and chronic
      kidney disease.
AB  - There is a remarkable lack of randomized trial data on optimal management of
      coronary artery disease (CAD) in patients with chronic kidney disease (CKD). In
      fact, patients with CKD are often excluded from randomized trials that compare
      different treatment strategies for CAD. Because the most common cause of death in
      CKD patients is cardiovascular disease, it is crucial that studies are designed
      to determine the best therapy for CAD in this high-risk group. This article
      discusses the available data on coronary revascularization outcomes in CKD
      patients.

PMID- 15241741
TI  - Optimal dialysis for the end-stage renal disease patient with cardiovascular
      disease.
AB  - The increasing incidence and prevalence of end-stage renal disease (ESRD) that
      requires renal replacement therapy has placed a focus on the dialysis procedure
      itself with respect to its hemodynamic and cardiovascular complications. More
      than 50% of patients with ESRD will die of cardiovascular disease (CVD). A
      considerable contribution to cardiovascular events occurs with the dialysis
      procedure itself. This paper explores the intradialytic complications of
      hemodialysis as they relate to the cardiovascular system and highlights
      opportunities for research and improved quality of care.

PMID- 15241742
TI  - Impact of kidney transplantation on the progression of cardiovascular disease.
AB  - Kidney transplantation, of all the treatment modalities for end-stage renal
      disease, affords the greatest potential for prolonged survival and improved
      quality of life. Great strides in immunosuppressant therapy have improved graft
      survival and forced clinicians to consider other health-care needs of kidney
      transplant recipients. Chief among these needs is the prevention and treatment of
      cardiovascular disease. Cardiovascular disease is the most common cause of death
      among patients with a working renal allograft. Because therapies for primary and
      secondary prevention are successful in the general population, transplant
      clinicians are increasingly focused on preventing or limiting the progression of
      cardiovascular disease. Initiation of aggressive management of conventional
      atherosclerotic risk factors and uremia-related risk factors, ideally during the
      early stages of chronic kidney disease (CKD) or after kidney transplantation, and
      efforts to delay the progression of kidney disease will hopefully reduce the
      cardiovascular burden in transplant recipients.

PMID- 15241743
TI  - Opportunities for improvement in the cardiovascular care of patients with end
      stage renal disease.
AB  - Cardiovascular disease accounts for the majority of morbidity and mortality in
      patients with end-stage renal disease (ESRD). Studies have identified several
      explanations for this observation, such as high rates of cardiovascular risk
      factors, lesser use of cardioprotective strategies, adverse outcomes with
      cardiovascular drugs and procedures, and accelerated atherosclerosis and
      myocardial disease in ESRD. Based on these findings, this article addresses the
      critical opportunities for improvement in cardiovascular outcomes in patients
      with ESRD. These improvements include prevention of cardiovascular events,
      management of acute coronary syndromes and heart failure, and the prevention of
      sudden death.

PMID- 15241744
TI  - Emergence of the concept of cardiovascular disease.
AB  - Historically, the concept of cardiovascular disease is a recent and evolving
      concept. Well into the eighteenth century, cardiac and vascular diseases were
      little known and considered a rarity. Description of the circulation by William
      Harvey (1578-1657) in 1628 marks the beginning of the changes that ensued.
      However, knowledge was slow to accrue and not until the nineteenth century was
      the heart taken as a specific object of study. The description of end-stage
      kidney disease by Richard Bright (1789-1858) in 1827 launched studies of the
      vasculature, which were to lead to the recognition of hypertension and subsequent
      identification of the lesions of arteriosclerosis (1833) and atherosclerosis
      (1904) as diseases of the vasculature. Only between the two world wars did the
      full impact of these lesions on mortality and morbidity come to be finally
      recognized. Their study and therapy has defined much of the profound changes that
      affected twentieth century medicine.

PMID- 15241745
TI  - Vascular biology in uremia: insights into novel mechanisms of vascular injury.
AB  - Cardiovascular disease is the leading cause of death in patients with end-stage
      renal disease. Although the prevalence of traditional atherosclerotic risk
      factors is increased in patients with chronic kidney disease, these traditional
      risk factors alone do not seem to account for the increased cardiovascular
      mortality. It has been proposed that additional risk factors may play a role in
      vascular injury. Among nontraditional risk factors, chronic inflammation,
      oxidative stress, and vascular calcification have been implicated in the
      accelerated athersclerosis of chronic kidney disease. Uremia is a proinflammatory
      state. Elevated levels of the proinflammatory cytokine interleukin-6 and
      suppressed levels of the anti-inflammatory cytokine interleukin-10 are present in
      chronic kidney disease and have been implicated in accelerated atherosclerosis.
      Uremia also results in increased oxidative stress. Asymmetric dimethyl arginine
      and myeloperoxidase may be critical mediators of the endothelial damage that
      results from oxidative stress. Finally, the uremic milieu seems to promote
      vascular calcification. The abundance of proinflammatory cytokines, the possible
      deficiency in calcification inhibitory proteins and the high phosphorus that are
      often present in uremia contribute to vascular calcification. Smooth muscle cells
      in calcifying lesions undergo phenotypic changes and molecular reprogramming that
      are reminiscent of endochondral bone formation during embryogenesis.

PMID- 15241746
TI  - The spectrum of cardiovascular disease in children with predialysis chronic
      kidney disease.
AB  - Cardiovascular disease is the major cause of mortality in adults and children on
      chronic dialysis and in adults after kidney transplantation. Cardiovascular
      disease burden and cardiovascular mortality are high in adults with chronic
      kidney disease. The early development of cardiovascular disease risk factors,
      some of which are modifiable, largely explain this phenomenon. Limited data are
      available on the prevalence of chronic kidney disease in children, the prevalence
      of cardiovascular disease in children with chronic kidney disease, and the
      prevalence of cardiovascular disease risk factors in these patients. This article
      summarizes the current knowledge of the prevalence of cardiovascular disease and
      of cardiovascular disease risk factors in pediatric patients with predialysis
      chronic kidney disease. Long-term prospective studies are needed to determine the
      impact of early identification and treatment of cardiovascular disease and its
      risk factors on the natural history of cardiovascular disease in children with
      chronic kidney disease.

PMID- 15241747
TI  - Cardiovascular diseases in kidney transplant recipients: the role of anemia.
AB  - Cardiovascular diseases are among the leading causes of mortality and death
      associated graft loss in kidney transplant recipients. Recently, there has been
      an increased awareness of the potential role of nontraditional risk factors such
      as anemia in contributing to the increased burden of cardiovascular diseases in
      kidney transplant recipients. Studies that are primarily based on retrospective
      data analyses have shown an association between anemia and cardiovascular
      outcomes. These findings underscore the need for prospective studies to better
      understand these risks and to implement management strategies that would have a
      positive impact on patient and graft outcomes. On the basis of the available
      data, this article reviews the magnitude of cardiovascular diseases and anemia in
      kidney transplant recipients with a focus on the role of anemia on cardiovascular
      outcomes in these patients.

PMID- 15241748
TI  - A prehabilitation program for the prevention of functional decline: effect on
      higher-level physical function.
AB  - OBJECTIVE: To determine whether a home-based physical therapy (PT) program
      prevented decline in several higher-level measures of physical function among
      physically frail, community-living older persons. DESIGN: Randomized controlled
      trial. SETTING: General community. PARTICIPANTS: Persons (N=188) who were
      physically frail and aged 75 years or older. INTERVENTION: A home-based PT
      program (ie, prehabilitation) that focused primarily on improving underlying
      impairments in physical capabilities. MAIN OUTCOME MEASURES: Self-reported
      instrumental activities of daily living (IADLs); mobility, as determined by a
      modified version of the Performance Oriented Mobility Assessment; timed rapid
      gait and timed chair stands; and integrated physical performance, as determined
      by a modified version of the Physical Performance Test, were assessed at
      baseline, 7 months, and 12 months. RESULTS: As compared with participants in the
      educational control group, participants in the intervention group had reductions
      in IADL disability of 17.7% at 7 months (P=.036) and 12.0% at 12 months (P=.143)
      and had gains, ranging from 7.2% to 15.6%, in mobility and integrated physical
      performance at 7 and 12 months. CONCLUSIONS: Our home-based prehabilitation
      program offered modest but consistent benefits for the prevention of decline in
      several higher-level measures of physical function.

PMID- 15241749
TI  - Cholinergic augmentation with donepezil enhances recovery in short-term memory
      and sustained attention after traumatic brain injury.
AB  - OBJECTIVE: To examine effects of donepezil on short-term memory and sustained
      attention in postacute patients with traumatic brain injury (TBI). DESIGN: A 24
      week, randomized, placebo-controlled, double-blind crossover trial. SETTING:
      Outpatient clinics in 2 teaching hospitals. PARTICIPANTS: Eighteen postacute TBI
      patients with cognitive impairment. INTERVENTION: Patients were randomly assigned
      to group A or group B. Patients in group A received donepezil for the first 10
      weeks and then a placebo for another 10 weeks. The 2 treatment phases were
      separated by a washout period of 4 weeks. Patients in group B received the
      preparations in the opposite order. MAIN OUTCOME MEASURES: Short-term memory and
      sustained attention were assessed by 2 indexes (Auditory Immediate Index [AII],
      Visual Immediate Index [VII]) of the Wechsler Memory Scale-III and the Paced
      Auditory Serial Addition Test (PASAT), at baseline, week 10, and week 24 of the
      trial. RESULTS: Intragroup comparison of different phases of the trial in both
      groups showed that donepezil significantly increased the testing scores of the
      AII and VII, as well as PASAT scores, compared with baseline. There was no
      significant change in the testing scores between assessment at baseline and the
      end of the placebo phase in group B. Intergroup comparison at the 10-week
      assessment showed significantly improved testing scores in group A with donepezil
      over group B with the placebo. The improved testing scores with donepezil in
      group A were sustained after the washout period and placebo phase, suggesting a
      carry-over effect of the medication. CONCLUSIONS: Donepezil increased
      neuropsychologic testing scores in short-term memory and sustained attention in
      postacute TBI patients. Cholinergic augmentation may be a viable approach to
      restore memory and attention after TBI.

PMID- 15241750
TI  - Effects of a late-phase exercise program after total hip arthroplasty: a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of a late-phase exercise program for
      patients who underwent total hip arthroplasty (THA) 4 to 12 months earlier.
      DESIGN: A single-blind, randomized controlled trial. SETTING: Exercises were
      performed in subjects' homes. Exercise instruction and measurements taken before
      and after the trial were performed in an outpatient research and treatment
      center. PARTICIPANTS: Convenience sample of 34 adults 4 to 12 months post-THA
      randomly allocated to experimental or control groups. Twenty-eight subjects
      completed the study. INTERVENTION: An 8-week, hip-exercise intervention, during
      which the control group received basic isometric and active range of motion
      exercises; the experimental group received strength and postural stability
      exercises. MAIN OUTCOME MEASURES: Score on the 12-Item Hip Questionnaire; fear of
      falling; hip flexor, extensor, abductor, and knee extensor muscle torque; and
      postural stability in single stance. RESULTS: There was a statistically
      significant improvement in all measures of self-perceived function, muscle
      strength (hip flexors, 24.4%; hip extensors, 47.8%; hip abductors, 41.2%; knee
      extensors, 23.4%), and postural stability (36.8%) in the experimental group and
      no significant change in the control group. Neither group had statistically
      significant changes in fear of falling measures. CONCLUSIONS: An exercise program
      emphasizing weight bearing and postural stability significantly improved muscle
      strength, postural stability, and self-perceived function in patients 4 to 12
      months after THA.

PMID- 15241751
TI  - Dose-dependent response to intramuscular botulinum toxin type A for upper-limb
      spasticity in patients after a stroke.
AB  - OBJECTIVE: To test the hypothesis that intramuscular (IM) botulinum toxin type A
      (BTX) reduces excessive muscle tone in a dose-dependent manner in the elbow,
      wrist, and fingers of patients who experience spasticity after a stroke. DESIGN:
      Randomized, double-blind, placebo-controlled, multicenter, 24-week trial.
      SETTING: Six academic and 13 private US outpatient medical centers. PARTICIPANTS:
      Ninety-one patients with a mean age of 60 years (range, 30-79 y). Mean time
      elapsed from ischemic or hemorrhagic stroke to study enrollment was 25.8 months
      (range, 0.9-226.9 mo). INTERVENTIONS: Up to 2 treatments of placebo, or 90, 180,
      or 360U of BTX. Concurrent splinting and physical therapy protocols were
      permitted, but no changes were allowed during the study. MAIN OUTCOME MEASURES:
      Wrist, elbow, and finger flexor tone assessed by the Modified Ashworth Scale,
      physician and patient global assessments, pain, FIM instrument, and Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Muscle tone
      decreased more with injections of BTX than with placebo in the wrist flexors at
      weeks 1, 2, 3, 6, and 9 (P< or =.026); in the elbow flexors at weeks 1, 2, 3, 4,
      5, and 9 (P< or =.033); and in the finger flexors at weeks 1 and 3 (P< or =.031).
      A dose-dependent response was generally observed in tone reduction but not in
      pain, FIM, or SF-36 measures. CONCLUSIONS: IM BTX reduced muscle tone in a dose
      dependent manner in the elbow, wrist, and fingers of patients who experience
      spasticity after a stroke but did not appear to affect global quality of life or
      disability.

PMID- 15241752
TI  - The effectiveness of anticoagulant and antiplatelet agents in preventing venous
      thromboembolism during stroke rehabilitation: a historical cohort study.
AB  - OBJECTIVE: To determine the effectiveness of anticoagulant and antiplatelet
      agents in preventing venous thromboembolism (VTE) during stroke rehabilitation.
      DESIGN: Historical cohort study. SETTING: Acute inpatient rehabilitation
      hospital. PARTICIPANTS: Consecutive patients (N=1506) with ischemic and
      hemorrhagic stroke admitted for rehabilitation. INTERVENTIONS: Documented use of
      anticoagulants (warfarin or anticoagulant doses of heparin), heparin in
      prophylactic doses, and antiplatelet agents. MAIN OUTCOME MEASURE: Occurrence of
      deep vein thrombosis detected by ultrasound or venography or pulmonary embolism
      detected by ventilation perfusion scan, spiral computed tomography, or pulmonary
      angiography. RESULTS: Fifty-eight VTE events occurred (3.9% incidence or 1.36
      events per 1000 patient days), with higher risk in patients with severe stroke.
      Only therapeutic anticoagulation had a statistically significant protective
      effect for VTE risk in univariate analysis (odds ratio [OR]=.44; 95% confidence
      interval [CI],.20-.98). After adjusting for multiple medication use and other
      factors, including age, stroke onset to admission interval, length of
      rehabilitation stay, cause of stroke, and admission National Institutes of Health
      Stroke Scale score, therapeutic anticoagulation gave strong protection against
      VTE (OR=.37; 95% CI,.15-.88), followed by heparin (OR=.48; 95% CI,.23-.98) but
      not by antiplatelet agents (OR=.79; 95% CI,.40-1.57). No medications were
      associated with significant bleeding complications. CONCLUSIONS: Use of
      therapeutic anticoagulants or prophylactic heparin prevented VTE in stroke
      patients during inpatient rehabilitation.

PMID- 15241753
TI  - Fine motor control in adults with and without chronic hemiparesis: baseline
      comparison to nondisabled adults and effects of bilateral arm training.
AB  - OBJECTIVES: To characterize fine motor control through finger tapping in both
      arms of 10 patients with chronic stroke, to make baseline comparisons with
      matched controls, and to examine the responsiveness of deficits seen in stroke
      patients after 6 weeks of bilateral arm-based training. DESIGN: Nonrandomized
      controlled, cohort before-after trial. SETTING: Research institution.
      PARTICIPANTS: Ten people from the community with chronic unilateral ischemic
      stroke and 10 age- and sex-matched healthy controls. Participants with
      hemiparesis had completed all conventional care and were more than 6 month
      poststroke. Inclusion criteria were at least 6 months since a unilateral stroke,
      ability to follow simple instructions and 2-step commands, volitional control of
      the nonparetic arm, and at least minimal antigravity movement in the shoulder of
      the paretic arm. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Measurements included rate and timing consistency of unilateral tapping at a
      preferred and a maximal rate and the accuracy and stability of interlimb
      coordination in bilateral simultaneous (inphase) and alternating (antiphase)
      tapping at a preferred rate. RESULTS: Nonparetic finger control was similar to
      that of the nondisabled participants except under bilateral conditions, where it
      was less consistent. A subgroup with residual paretic finger function, had slower
      and less consistent paretic finger tapping, as well as less accurate and more
      variable interlimb coordination; however, basic bilateral coupling relationships
      were preserved. Bilateral arm-based training improved bilateral nonparetic
      consistency but slowed unilateral preferred tapping. Training also improved
      paretic fine motor control in 2 of 4 participants with mild stroke severity. The
      2 responders, with dominant hemisphere lesions, indicated a possible recovery
      advantage with bilateral training for such lesions. CONCLUSIONS: In general,
      nonparetic finger control for tapping was preserved but paretic finger control
      was compromised. Disruption of nonparetic control of tapping, particularly
      consistency of tapping, occurred during bilateral tapping tasks but was
      responsive to 6 weeks of bilateral arm-based training. Despite the apparent lack
      of training specificity, the generalizable effects of bilateral arm training to
      fine motor interlimb coordination may reflect central motor control mechanisms
      for upper-extremity coordination, which may be accessed and may influence the
      recovery of arm function after stroke.

PMID- 15241754
TI  - The effect of poststroke cognitive impairment on rehabilitation process and
      functional outcome.
AB  - OBJECTIVES: To determine whether cognitive impairment affects access to, or
      quality of, rehabilitation services, and to examine the effects of functional
      outcomes in stroke patients. DESIGN: Secondary analysis of prospective cohort of
      stroke patients followed for 6 months after stroke. SETTINGS: Eleven large-volume
      US Department of Veterans Affairs hospitals nationwide. PARTICIPANTS: Stroke
      patients (N=272) who were candidates for rehabilitation. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Rehabilitation process variables were examined
      for patients assessed as cognitively impaired or unimpaired according to
      education-adjusted Mini-Mental State Examination score. Functional outcomes were
      performance of activities of daily living (ADLs), measured by the FonFIM, and
      instrumental activities of daily living (IADLs), measured by Lawton, at 6-month
      follow-up. RESULTS: Compliance with guidelines and receipt of and interval to
      postacute treatment initiation did not differ between cognitively impaired and
      unimpaired patients. Although most cognition-related treatment elements were
      similar for both groups, cognitive goals were more frequently charted in impaired
      patients. Controlling for baseline function and rehabilitation process,
      cognitively impaired patients had worse IADL performance at 6 months than did
      unimpaired patients; cognition did not significantly influence ADL performance.
      CONCLUSIONS: Quality of, and access to, rehabilitative care was equivalent for
      patients with and without cognitive impairment. Despite a similar rehabilitation
      process, cognitively impaired stroke patients experienced worse recovery of
      IADLs.

PMID- 15241755
TI  - Value of the D-dimer test in diagnosing deep vein thrombosis in rehabilitation
      inpatients.
AB  - OBJECTIVE: To assess the utility of the D-dimer test-a widely available, less
      costly, and less time-consuming test than others used to diagnose or exclude deep
      vein thrombosis (DVT) and pulmonary embolism. DESIGN: Blind comparison. SETTING:
      An inpatient rehabilitation facility in Turkey. PARTICIPANTS: Sixty-eight
      consecutive inpatients being rehabilitated after stroke, spinal cord injury, hip
      arthroplasty, or traumatic brain injury. INTERVENTIONS: A latex D-dimer assay was
      performed on each patient at admission and then weekly throughout the hospital
      stay. Color Doppler ultrasonography of the lower limbs was also done for each
      patient at admission and was repeated when indicated by clinical signs and
      symptoms of DVT or by elevated D-dimer levels. Main outcome measures Patients'
      clinical findings, D-dimer test results, and ultrasonography results were
      recorded. Sensitivity, specificity, and positive and negative predictive values
      were calculated for the D-dimer test, each clinical finding, and combinations of
      D-dimer results and clinical findings in relation to DVT diagnosis. RESULTS: The
      sensitivity and negative predictive value of the D-dimer test were high, at 95.2%
      and 96.2%, respectively. The specificity and positive predictive value were low,
      at 55.3% and 48.7%, respectively. No single clinical finding was reliably
      diagnostic for DVT. CONCLUSIONS: The D-dimer assay is a reliable method for
      ruling out DVT. In the rehabilitation setting, it can be used as a routine
      screening test or to assess cases of suspected DVT. D-dimer testing may reduce
      the need for sophisticated, time-consuming, and expensive diagnostic workup of
      rehabilitation inpatients, a group that is at increased risk for DVT.

PMID- 15241757
TI  - Reliability of transcutaneous oxygen tension measurement on the back of the hand
      and complex regional pain syndrome after stroke.
AB  - OBJECTIVE: To verify the reproducibility of measurement of transcutaneous oxygen
      tension (TcPo(2)) on the back of the hand in control subjects and stroke patients
      in the assessment of the complex regional pain syndrome type I (CRPS I). DESIGN:
      Case series study. SETTING: Physical medicine and rehabilitation department at a
      university hospital. PARTICIPANTS: Eighteen control subjects, 30 stroke patients
      without CRPS I, and 12 stroke patients with CRPS I. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: TcPo(2) was measured on the back of hands on 2
      consecutive days using a polarographic technique. The reproducibility was
      evaluated by using the intraclass correlation coefficient (ICC) and the
      coefficient of variation. RESULTS: In the controls, the values of TcPo(2) were
      not reproducible, with an ICC of.51 (95% confidence interval [CI],.23-.72).
      Similarly, in the hemiplegics with and without CRPS I, TcPo(2) was not
      reproducible, with an ICC of.43 (95% CI, -.15 to.74) and.69 (95% CI,.45-.84),
      respectively. The differences between the 2 upper limbs were even less
      reproducible in each population. CONCLUSIONS: Measurement of TcPo(2) on the hand
      using our procedure did not seem to be sufficiently reproducible for application
      to a pathology such as CRPS I.

PMID- 15241756
TI  - Evaluation of postural stability in the elderly with stroke.
AB  - OBJECTIVE: To compare clinical and biomechanical measures of balance in elderly
      stroke patients with those of healthy elderly people. DESIGN: Two-group
      comparison design. SETTING: Laboratory environment. PARTICIPANTS: Fifteen
      poststroke patients and 15 healthy age-matched older adults (N=30).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The biomechanical variable
      COP-COM, which represents the distance between the center of pressure (COP) and
      the center of mass (COM) in terms of root mean square. The mean of 4 trials of
      the COP-COM variable for each test condition was used for statistical analysis.
      Furthermore, the different systems (sensory, motor, central processor) related to
      postural stability were evaluated. RESULTS: Statistical significance of the COP
      COM variable was larger in the stroke group than in healthy subjects, in both the
      anteroposterior (AP) and mediolateral (ML) directions. Furthermore,
      statistically, stroke subjects showed amplitudes of the COP-COM variable that
      were significantly larger in the eyes-closed condition. The significant negative
      correlation demonstrated between COP-COM amplitude and the balance scales (Berg,
      Tinetti) indicated that the patients with larger COP-COM amplitudes had lower
      clinical balance score. Furthermore, correlation coefficient scores between COP
      COM variables in both AP and ML directions and motor performance using Fugl-Meyer
      Assessment (rho=-.53, rho=-.51, respectively) and reaction time (rho=-.53, rho=
      .44, respectively) were significant. Vibration (rho=.41) and touch-pressure
      (rho=.42) perception thresholds correlated significantly only in the AP
      direction. CONCLUSIONS: Evaluating postural stability with COP-COM variable
      provided an accurate measure of postural stability in poststroke elderly people.
      Furthermore, postural stability in quiet stance, as measured by COP-COM
      amplitude, was related to functional measures of balance as well as physiologic
      factors relating to balance, such as visual conditions, lower-extremity
      peripheral sensibility, motor recovery, and simple reaction time.

PMID- 15241758
TI  - Robotic therapy for chronic motor impairments after stroke: Follow-up results.
AB  - OBJECTIVES: To study the effects of robotic rehabilitation in persons with
      chronic motor impairments after stroke and to examine whether improvements in
      motor abilities were sustained 4 months after the end of therapy. DESIGN: Pretest
      posttest design. SETTING: Rehabilitation hospital, outpatient care. PARTICIPANTS:
      Volunteer sample of 42 persons with persistent hemiparesis from a single,
      unilateral stroke within the past 1 to 5 years. INTERVENTION: Robotic therapy for
      the paretic upper limb consisted of either sensorimotor active-assistive
      exercise, or progressive-resistive training during repetitive, planar reaching
      tasks, 3 times a week for 6 weeks. MAIN OUTCOME MEASURES: Modified Ashworth
      Scale, Fugl-Meyer Assessment (FMA), Motor Status Scale (MSS) score, and Medical
      Research Council motor power score. RESULTS: No significant differences were
      found among pretreatment clinical evaluations. Statistically significant gains
      from admission to discharge and from admission to follow-up (P<.05) were found on
      the FMA, MSS score for shoulder and elbow, and motor power score. CONCLUSIONS:
      Short-term, goal-directed robotic therapy can significantly improve motor
      abilities of the exercised limb segments in persons with chronic stroke that are
      sustained 4 months after discharge. This suggests that motor recovery can be
      enhanced by repetitive exercise training more than 1 year after stroke.

PMID- 15241759
TI  - Neuromuscular electric stimulation enhances endothelial vascular control and
      hemodynamic function in paretic upper extremities of patients with stroke.
AB  - OBJECTIVE: To investigate the effects of neuromuscular electric stimulation
      (NMES) on endothelial vascular control and hemodynamic function in patients in
      rehabilitation after acute stroke. DESIGN: Before-after trial. SETTING:
      Inpatients in a tertiary hospital. PARTICIPANTS: Sixteen stroke patients (11
      women, 5 men) with a mean age of 60.6+/-19.5 years. INTERVENTIONS: All patients
      received NMES for paretic wrist extensor and flexor muscles 30 minutes daily, 5
      days a week, for 4 weeks. The nonparetic upper extremities, which served as
      controls, did not receive NMES. MAIN OUTCOME MEASURES: Laser Doppler perfusion
      testing was conducted to measure cutaneous microcirculatory responses to
      transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP),
      as specific endothelium-dependent and -independent vasodilators, respectively.
      Arterial and venous hemodynamic function was also measured by impedance
      plethysmography. RESULTS: Before NMES treatment, the venous capacity and
      compliance of the paretic extremities did not differ significantly from those of
      the nonparetic extremities. However, hyperemic arterial inflow, ACh-induced
      cutaneous perfusion, and the ratio of ACh- to SNP-induced cutaneous perfusion
      were lower in the paretic than in the nonparetic extremities. After NMES
      treatment, hyperemic arterial inflow and venous outflow increased by 21.5% and
      57.2%, respectively, in the paretic extremities (P<.05). ACh-induced cutaneous
      perfusion and the ratio of ACh- to SNP-induced cutaneous perfusion were also
      significantly enhanced in the paretic extremities. In contrast, hyperemic
      arterial inflow decreased by 39.6% in the nonparetic extremities (P<.05), and
      endothelium-dependent cutaneous vasodilation also decreased significantly.
      CONCLUSIONS: NMES therapy may enhance the hyperemic arterial response and
      endothelium-dependent dilation in skin vasculature in the paretic upper
      extremities of patients with stroke.

PMID- 15241760
TI  - Phenol block for cervical dystonia: effects and side effects.
AB  - OBJECTIVE: To report on the effectiveness and side effects of 2% phenol block in
      patients with cervical dystonia (CD). DESIGN: Case series. SETTING: A
      rehabilitation department at a university medical center in Japan. PARTICIPANTS:
      Sixteen patients (11 men, 5 women; mean age +/- standard deviation, 43.4+/-11.2y)
      with CD. The cause of the CD was unknown, and all cases were refractory to the
      oral medication and rehabilitation therapy. INTERVENTION: Two percent phenol
      blocks guided by electromyography. MAIN OUTCOME MEASURES: A blind analysis by
      neurologists of the Tsui score before and after 2 weeks of treatment with phenol
      block. Side effects were evaluated by another neurologist and patient report.
      RESULTS: There was significant (P=.0002) improvement in neck movement and
      position, based on a reduced Tsui score, after the phenol block. However, 4
      patients had a complication of sensory disturbance of the transverse cutaneous
      nerve of the neck area. The sensory disturbances decreased gradually and
      disappeared within 3 months, whereas the effects of the phenol block continued.
      CONCLUSIONS: Phenol block can reduce the impact of CD that is refractory to
      therapy.

PMID- 15241761
TI  - Combining botulinum toxin and phenol to manage spasticity in children.
AB  - OBJECTIVE: To describe the specific techniques and adverse reactions of using
      concurrent, multiple injections of both botulinum toxin and phenol to manage
      spasticity in children with cerebral palsy (CP) and other neurologic conditions.
      DESIGN: A retrospective case series. SETTING: A tertiary care children's
      hospital. PARTICIPANTS: Consecutive patients (N=68) with spasticity related to CP
      or other neurologic conditions. INTERVENTION: Ninety injection sessions combining
      botulinum toxin and phenol to manage spasticity. MAIN OUTCOME MEASURE:
      Documentation of adverse reactions. RESULTS: The mean phenol dosage was 9.5mL at
      a mean of 0.6mL/kg per injection dose. The mean botulinum toxin type A (Botox)
      dose injected was 193U (12U/kg), and the mean of botulinum toxin type B (Myobloc)
      dose injected was 7750U (530U/kg). The mean number of muscles injected was 14.
      Adverse reactions are described but were infrequent. Dysesthetic hand pain
      occurred in 2 patients. One patient developed a systemic reaction to Myobloc.
      CONCLUSIONS: Using botulinum toxin and phenol injections allowed many muscles to
      be injected to manage spasticity in children with CP and other neurologic
      conditions. Using this combination allowed an increased number of injections at
      the maximal recommended dose.

PMID- 15241762
TI  - Tizanidine for the treatment of intention myoclonus: a case series.
AB  - OBJECTIVE: To evaluate the effectiveness of tizanidine in treating intention
      myoclonus. DESIGN: Case series. SETTING: Inpatient rehabilitation center.
      PARTICIPANTS: Three subjects whose activities of daily living were impaired due
      to intention myoclonus related to mitochondrial encephalomyopathy, stroke, and
      multiple sclerosis (MS). INTERVENTION: Tizanidine. MAIN OUTCOME MEASURES:
      Reduction in intention myoclonus and change in score on the FIM instrument.
      RESULTS: The patient with mitochondrial encephalomyopathy had left upper- and
      lower-extremity intention myoclonus; the patient with stroke had left upper
      intention myoclonus; and the patient with MS had right upper- and left lower
      intention myoclonus. In the patient with mitochondrial encephalomyopathy, the FIM
      score increased from 90 to 103 points over 2 days of tizanidine. The stroke
      patient's FIM score improved only from 74 to 79 after 4 weeks of tizanidine. The
      patient with MS improved from 83 to 101 after 6 days of tizanidine. All 3
      patients had almost full resolution of the intention myoclonus. All continued on
      tizanidine except the patient with stroke, who had minimal gains and a low
      systolic blood pressure. None of the patients experienced significant sedation or
      hypotension. CONCLUSIONS: Tizanidine may be a safe and effective option for
      treating intention myoclonus that occurs in a variety of neurologic conditions.

PMID- 15241763
TI  - Rating scale analysis of the Berg Balance Scale.
AB  - OBJECTIVES: To examine, using Rasch analysis, the rating scale performance of the
      Berg Balance Scale (BBS) and to describe the 45/56 cutoff score in functional
      terms. DESIGN: Retrospective chart review of BBS scores. Rasch rating scale
      analysis was performed on these data. SETTING: Outpatient Veterans Affairs
      medical center. PARTICIPANTS: One hundred (99 men, 1 woman) community-dwelling
      veterans referred for balance deficits (age range, 64-88y). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The BBS. RESULTS: Condensing item-rating
      categories allowed the elimination of underutilized categories and constructed
      categories that better separated people of differing abilities. Rating pivot
      points were developed for each item to represent a transition between passing and
      failing. Following pivot-point development and rating scale rescoring, person and
      item measures became more evenly distributed across the BBS and resulted in
      changes in item difficulty order. In our sample, functional indicators of a score
      of at least 45/56 were a rating of passing the item "tandem stance," as well as
      passing 2 of the following 3 items: "alternating foot," "standing on one leg,"
      and "look behind." CONCLUSIONS: Our findings provide direction for improving the
      rating scale structure for each of the items and establish a connection between
      the BBS cutoff score of 45/56 and functional ability.

PMID- 15241764
TI  - Pressure mapping in seating: a frequency analysis approach.
AB  - OBJECTIVES: To discuss the methodologic challenges related to pressure mapping in
      seating and to present a new approach to the analysis and interpretation of
      results: the frequency analysis approach. DESIGN: Pressure mapping was performed
      on 3 prototypes of a newly developed foam and gel seat cushion. SETTING: Data
      collection was done in a private laboratory. PARTICIPANTS: Eight nondisabled men.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Average pressure, peak
      values, and the size of the contact area were measured continuously for 74
      minutes on each cushion prototype. A supplementary frequency analysis provided
      information on the number of times each value occurred during the measurement
      period. RESULTS: Average pressure and peak values showed only very small,
      nonsignificant changes over the measurement period for all variants. The
      frequency analysis, however, showed significant differences that enabled the
      manufacturer to select the prototype best suited for further development.
      CONCLUSIONS: Verifying significant differences in pressure-relieving properties
      between products has to date been difficult. Findings from this study indicate
      that a frequency analysis approach may enable more adequate and precise ways to
      perform such studies.

PMID- 15241765
TI  - Relation between median and ulnar nerve function and wrist kinematics during
      wheelchair propulsion.
AB  - OBJECTIVE: To investigate the relation between median and ulnar nerve health and
      wrist kinematics in wheelchair users. DESIGN: Case series. SETTING: Biomechanics
      laboratory and electrodiagnostic laboratory at a Veterans Health Administration
      medical center and a university hospital, respectively. PARTICIPANTS: Thirty-five
      people with spinal cord injury who use manual wheelchairs. INTERVENTION: Subjects
      propelled their own wheelchair on a dynamometer at 0.9 and 1.8m/s. Bilateral
      biomechanic data were obtained by using force and moment sensing pushrims and a
      kinematic system. Bilateral median and ulnar nerve conduction studies were also
      completed. MAIN OUTCOME MEASURES: Wrist flexion, extension, radial and ulnar
      deviation peaks, and ranges of motion (ROMs) as related to median and ulnar motor
      and sensory amplitudes. A secondary analysis included peak pushrim forces and
      moments and stroke frequency. RESULTS: There was a significant, positive
      correlation between flexion and extension ROM and both ulnar motor amplitude
      (r=.383, P<.05) and median motor amplitude (r=.361, P<.05). CONCLUSIONS: Contrary
      to our hypothesis, subjects using a greater ROM showed better nerve function than
      subjects propelling with a smaller ROM. Subjects using a larger ROM used less
      force and fewer strokes to propel their wheelchairs at a given speed. It is
      possible that long, smooth strokes may benefit nerve health in manual wheelchair
      users.

PMID- 15241766
TI  - Wheelchair back-support options: functional outcomes for persons with recent
      spinal cord injury.
AB  - OBJECTIVE: To evaluate the functional outcomes for people with a recent spinal
      cord injury (SCI) when using 3 different back-support options. DESIGN: Repeated
      measures within-subject comparison. SETTING: Rehabilitation center. PARTICIPANTS:
      Twenty-seven manual wheelchair users with recent SCI. INTERVENTIONS: Three types
      of wheelchair back supports--a standard sling upholstery, a Jay J2 back, and a
      Pindot PaxBac--were used by each participant to evaluate performance of 4
      functional tasks. MAIN OUTCOME MEASURES: Functional tasks included timed forward
      wheeling, ramp ascent, distance for forward vertical reach, and 1-stroke push.
      Product satisfaction was also rated. RESULTS: For most participants, best
      performance for each task varied with back support used. Significant differences
      in functional performance were found for the reaching activity (P=.01), with
      greater reach when the J2 was used. Satisfaction ratings also differed
      significantly (P=.017), with participants indicating greater satisfaction with
      the J2. Participants' choice of back support varied and did not consistently
      correspond with best performance. CONCLUSIONS: Except for reaching, performance
      of functional activities did not differ depending on back support used. Objective
      evaluation of reaching ability may assist in product decision making. Inclusion
      of a consistent battery of functional tasks could provide a standardized
      reference point for clients' subjective evaluations.

PMID- 15241767
TI  - A new method to quantify demand on the upper extremity during manual wheelchair
      propulsion.
AB  - OBJECTIVE: To use an ergonomics-based rating that characterizes both demand on,
      and capacity of, upper-extremity muscle groups during wheelchair propulsion to
      help identify the muscle groups most at risk for pain or overuse injury in a
      relatively demanding wheelchair propulsion task. DESIGN: Case series. SETTING:
      Biomechanics research laboratory. PARTICIPANTS: Sixteen manual wheelchair users
      with complete (American Spinal Injury Association grade A) T6-L2 paraplegia.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Internal peak joint moments
      required by each of the major upper-extremity muscle groups for propelling a
      wheelchair up a ramp; isometric strength of each of the muscle groups in
      positions simulating wheelchair propulsion; and wheelchair propulsion strength
      rating (WPSR) for each muscle group, calculated by normalizing the joint demands
      to their capacity. RESULTS: The largest joint moment was for shoulder flexion, at
      39.7+/-13.9Nm. Shoulder flexion also accounted for the peak WPSR value of 66.5%+/
      20.3%. Supination and pronation movements had low peak moment requirements
      (3.4Nm, 5.0Nm, respectively) but high WPSR values (41%, 53%, respectively).
      CONCLUSIONS: Even a relatively benign ramp (2.9 degrees ) places a large demand
      on the musculature of the upper extremity, as assessed by using the WPSR to
      indicate muscular demand.

PMID- 15241768
TI  - Wheelchair skills training program for clinicians: a randomized controlled trial
      with occupational therapy students.
AB  - OBJECTIVE: To test the hypothesis that a brief formalized period of wheelchair
      skills training, added to the standard curriculum, results in significantly
      greater overall improvements in wheelchair skills than a standard undergraduate
      occupational therapy (OT) curriculum alone. SETTING: Rehabilitation center.
      DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty-two students in a
      university undergraduate OT program. INTERVENTIONS: All students received the
      standard university curriculum. The 22 second-year students, randomly allocated
      to the Wheelchair Skills Training Program (WSTP) group, were also trained (on a
      single occasion each, in groups of 1-3 at a time) on the 50 skills that make up
      the WSTP. The mean +/- standard deviation (SD) training time was 121.2+/-33.5
      minutes per group. MAIN OUTCOME MEASURE: Total percentage score on the Wheelchair
      Skills Test (WST), Version 2.4. RESULTS: From before to after intervention,
      second-year students in the WSTP group increased their mean percentage WST scores
      +/- SD from 64.8%+/-9.0% to 81.0%+/-5.2%, a 25% improvement (P<.001). Over a
      comparable period, the 18 students in the second-year control group increased
      from 66.0%+/-8.0% to 72.4%+/-7.1%, a 9.7% improvement (P=.015). The WSTP group
      improved to a significantly greater extent (P=.005). For a subset of 8 students
      in the WSTP group who were retested 9 to 12 months later, the mean WST score was
      79.7%+/-4.1%, not significantly less than their WST 2 scores (P=.29). The mean
      WST score for the 42 students in the fourth-year control group was 73.9%+/-4.1%,
      significantly lower than the mean postintervention WST score of the second-year
      students in the WSTP group (P< .0001) and not different from the second-year
      control group (P=.58). CONCLUSIONS: The WSTP is an effective way to improve the
      wheelchair-skills performance of OT students. This has implications for the
      education of all rehabilitation clinicians.

PMID- 15241769
TI  - Between-days reliability of H-reflexes in human flexor carpi radialis.
AB  - OBJECTIVES: To assess between-day reliability of the latency and peak-to-peak
      amplitude of a technique to elicit the H-reflex and M response of the flexor
      carpi radialis (FCR) and the ratio of maximum H-reflex and M-response amplitude
      (Hmax/Mmax). DESIGN: Test-retest reliability study. SETTING: Electrophysiology
      laboratory at a university. PARTICIPANTS: Fifteen consecutively recruited healthy
      volunteers (8 men, 7 women; age range, 22-65y). INTERVENTION: Volunteers were
      tested on 2 separate days at the same time of day for H-reflex and M response by
      stimulating the median nerve in the cubital fossa in the presence of a
      standardized voluntary contraction of the FCR muscle. MAIN OUTCOME MEASURES:
      Onset latencies, peak-to-peak amplitudes, and Hmax/Mmax. RESULTS: Latency
      measurements of H-reflex and M response showed excellent reliability between
      days, as did the maximum amplitude of the M response. The maximum amplitudes of
      the H-reflex and Hmax/Mmax ratio were less reliable but still within acceptable
      limits. CONCLUSIONS: The H-reflex and M response can be reliably elicited in the
      FCR. This technique provides a useful clinical tool for diagnostic purposes
      during the course of neurologic disorders and in preclinical and postclinical
      intervention studies.

PMID- 15241770
TI  - Changes in macro electromyography over time in patients with a history of polio:
      a comparison of 2 muscles.
AB  - OBJECTIVE: To investigate whether changes over time are different in a weight
      bearing leg muscle than in a less heavily used arm muscle. DESIGN: Prospective
      study. SETTING: University hospital laboratory. PARTICIPANTS: Twenty-three
      patients with a history of poliomyelitis. INTERVENTION: Two investigations were
      performed 5 years apart, using macro electromyography and the patients' own
      assessments of symptoms in the tibial anterior and the biceps brachii muscles.
      Test-retest of macro electromyography was performed in controls and in patients
      with old polio. MAIN OUTCOME MEASURES: Macro motor unit potential (MUP) and
      symptoms in the tibial anterior and biceps brachii over time. RESULTS: The macro
      MUP amplitude increased by 24% (P<.05) in the tibial anterior but was unchanged
      in the biceps brachii muscle. CONCLUSIONS: An increase in the macro MUP amplitude
      of the tibial anterior muscle, but not of the biceps brachii, most likely
      indicates a more pronounced ongoing denervation-reinnervation process over time
      in the tibial anterior. This difference could be activity dependent, but other
      factors cannot be excluded.

PMID- 15241771
TI  - Intensity and duration threshold for aerobic exercise-induced analgesia to
      pressure pain.
AB  - OBJECTIVE: To examine how exercise-induced analgesia is affected by the duration
      and intensity of aerobic exercise. DESIGN: Repeated-measures design. SETTING:
      Exercise science laboratory. PARTICIPANTS: Convenience sample of 12 healthy male
      and female volunteers (mean age +/- standard deviation, 32+/-9 y). INTERVENTIONS:
      Pain ratings were assessed before and at 5 and 30 minutes after treadmill
      exercise of 10 minutes at 75% maximal oxygen uptake (Vo(2)max), 30 minutes at 50%
      Vo(2)max, and 30 minutes at 75% Vo(2)max (randomized order and no less than 48 h
      between each bout). MAIN OUTCOME MEASURES: Pain ratings were measured on a visual
      analog scale at 10-second intervals during a 2-minute pressure-pain stimulus to
      the nondominant index finger. RESULTS: Pain ratings were significantly decreased
      (P<.05) from pre-exercise values 5 minutes after 30 minutes of exercise at 75%
      Vo(2)max but returned toward baseline by 30 minutes after exercise. There were no
      significant changes in pain ratings after 10 minutes of exercise or after
      exercise at 50% Vo(2)max. CONCLUSIONS: There are thresholds for both the
      intensity (>50% Vo(2)max) and duration (>10 min) of exercise required to elicit
      exercise analgesia.

PMID- 15241772
TI  - Medicaid payment for telerehabilitation.
AB  - OBJECTIVE: To assess current payment practice for telerehabilitation in state
      Medicaid programs. DESIGN: Telephone survey. SETTING: State Medicaid programs.
      PARTICIPANTS: State Medicaid directors. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Descriptive. RESULTS: Half of the 35 state Medicaid programs
      contacted reimbursed at least some telemedicine services other than radiology in
      2002. The primary reason for reimbursing for telemedicine is to make services
      available when there is no local practitioner. Consultation and evaluation and
      management services were most likely to be reimbursed (12 states). Seven state
      programs reimbursed telepsychology, and 4 states reported reimbursing for
      telespeech and language pathology, physical therapy, or occupational therapy.
      CONCLUSIONS: Telemedicine helps Medicaid programs deliver specialized care to
      locations with provider shortages. Telerehabilitation is not yet widespread,
      despite its potential benefit to people with disabilities who cannot travel to a
      clinic for rehabilitation therapy. Most Medicaid programs calculate the financial
      costs and patient benefits when considering payment policies, and about half of
      states require a state law to allow payment for telerehabilitation. Minnesota,
      Hawaii, and Nebraska, among the responding states, currently reimburse for
      telerehabilitation. Research is needed to evaluate the appropriateness of
      telerehabilitation for Medicaid beneficiaries.

PMID- 15241773
TI  - Recognition of psychiatric disorders in musculoskeletal and cardiovascular
      rehabilitation patients.
AB  - OBJECTIVE: To investigate the detection rate of psychiatric disorders in
      rehabilitation inpatients with musculoskeletal and cardiovascular diseases
      (CVDs). DESIGN: Cross-sectional survey; analysis of medical charts and discharge
      reports, combined with standardized diagnostic interviews. SETTING: Four
      orthopedic and 6 cardiovascular rehabilitation hospitals in southwest Germany.
      PARTICIPANTS: More than 1700 inpatients with different musculoskeletal disorders
      and CVDs participated in the survey. On the basis of their General Health
      Questionnaire score, 205 patients with musculoskeletal diseases and 164 patients
      with CVDs were selected randomly for standardized interviews. Discharge reports
      of interviewed patients were analyzed. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Clinical interview (Composite International Diagnostic
      Interview [CIDI]) to obtain diagnoses of psychiatric disorders as defined by the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
      Assessment of psychosocial burden and diagnoses of mental disorders, as well as
      admission to psychologic treatments, based on discharge reports of the attending
      physicians. RESULTS: The detection rate (sensitivity) of mental disorders was 48%
      in the orthopedic rehabilitation patients and 32% in the cardiovascular patients.
      Specificity was 80% in musculoskeletal patients and 87% in cardiovascular
      patients. Differential diagnostic competencies were lacking, and only half of the
      physicians' diagnoses corresponded to the CIDI diagnoses. CONCLUSIONS: The
      results showed a need for current DSM-IV or International Classification of
      Diseases, 10th edition, psychodiagnostics in medical rehabilitation to detect
      mental disorders in patients in the rehabilitation process at an earlier stage
      and to refer patients with comorbid mental disorders to adequate treatment.

PMID- 15241774
TI  - Hyperbaric oxygen therapy for traumatic brain injury: a systematic review of the
      evidence.
AB  - OBJECTIVE: To identify the benefits and harms of hyperbaric oxygen therapy (HBOT)
      to treat traumatic brain injury (TBI). DATA SOURCES: MEDLINE, EMBASE, the
      Cochrane Library, HealthSTAR, CINAHL, MANTIS, professional society databases, and
      reference lists. Databases were searched from inception through December 2003.
      STUDY SELECTION: We included English-language studies of patients with TBI given
      HBOT and evaluating functional health outcomes. DATA EXTRACTION: Data were
      abstracted by 1 reviewer and checked by a second. Study quality was rated as
      good, fair, or poor. DATA SYNTHESIS: Two fair-quality randomized controlled
      trials of patients with severe brain injury reported conflicting results. One
      found no difference in mortality (48% HBOT vs 55% control) or morbidity at 1
      year. In young patients with brainstem contusion, significantly more regained
      consciousness at 1 month with HBOT (67%) than control (11%) (P<.03). The other
      found a significant decrease in mortality in the HBOT group at 1 year (17%)
      compared with controls (31%) (P=.037). This decrease in mortality was accompanied
      by an increase in proportion of patients with severe disability. Patients with
      intracranial pressure (ICP) greater than 20 mmHg or a Glasgow Coma Scale score of
      4 to 6 had significantly lower mortality at 1 year than controls. Five
      observational studies did not provide better evidence of effectiveness or adverse
      events. Two indicated a potential for initially reducing elevated ICP in some
      patients. However, rebound elevations higher than pretreatment levels occurred in
      some patients. Adverse events, including seizures, pulmonary symptoms, and
      neurologic deterioration, were reported; however, no study systematically
      assessed adverse events, and none reported adverse events in control groups.
      CONCLUSIONS: The evidence for HBOT for TBI is insufficient to prove effectiveness
      or ineffectiveness, and more high-quality studies are needed. The evidence
      indicates that there is a small chance of a mortality benefit, which may depend
      on subgroup selection. The effect on functional status and the incidence and
      clinical significance of adverse effects are unclear.

PMID- 15241775
TI  - Streptococcal infection and necrotizing fasciitis--implications for
      rehabilitation: a report of 5 cases and review of the literature.
AB  - Five cases are presented of patients who were diagnosed with necrotizing
      fasciitis secondary to (1) hip disarticulation (in a paraplegic patient); (2)
      tooth abscess with extensive neck dissection, complicated by sepsis and
      hypotension with resultant dysphagia and ischemic encephalopathy; (3) below-knee
      amputation, anoxia, and severe debility; (4) emergent above-knee amputation; and
      (5) percutaneous endoscopic gastrostomy placement. The latter patient developed
      abdominal and chest wall necrotizing fasciitis that required skin grafting. Four
      patients were treated in an acute rehabilitation setting and returned home, and
      the fifth was rehabilitated in a subacute facility. This report emphasizes the
      importance of carefully monitoring rehabilitation patients, especially those with
      impaired sensation.

PMID- 15241776
TI  - A subclinical impairment of ventilatory function in cervical spondylotic
      myelopathy.
AB  - OBJECTIVE: To evaluate the ventilatory function in patients with cervical
      spondylotic myelopathy (CSM). DESIGN: Prospective cohort study. SETTING: Medical
      school in Japan. PARTICIPANTS: Thirty-seven consecutive patients with CSM.
      INTERVENTIONS: All the patients had surgical intervention for mild to moderate
      spastic limb paresis. MAIN OUTCOME MEASURES: Analysis of the maximum voluntary
      ventilation (MVV) in addition to routine spirometry before and after surgical
      decompression. Functional assessment was made by using the Japanese Orthopaedic
      Association (JOA) Scale. RESULTS: The MVV (% predicted) increased significantly
      (P<.002) from 77%+/-19% preoperatively to 84%+/-20% postoperatively. None of the
      other routine spirometric data (ie, vital capacity, forced vital capacity, forced
      expired volume in 1 second, peak expiratory flow rate) increased significantly.
      According to the JOA score, tetraparesis improved significantly (P<.0001) from
      8.3+/-3.2 preoperatively to 11.4+/-3.0 postoperatively. The ratio of
      postoperative to preoperative MVV showed a significant correlation (r=.538,
      P<.002) with that of the JOA score. CONCLUSIONS: MVV provides a useful measure
      for monitoring ventilatory impairment in patients with myelopathy.

PMID- 15241778
TI  - Optimization of an siRNA-expression system with an improved hairpin and its
      significant suppressive effects in mammalian cells.
AB  - BACKGROUND: RNA interference (RNAi) is a phenomenon in which expression of an
      individual gene can be specifically silenced by introducing a double-stranded
      RNA, one complementary to the gene, into cells. This phenomenon can be observed
      in mammalian cells when small interfering RNAs (siRNAs) are used, and is
      receiving attention as the most powerful tool for reverse genetics in the post
      genome era. Several groups have developed vector-based siRNA-expression systems
      that can induce RNAi in living cells. METHODS: We describe here a comparative
      analysis of various siRNA-expression systems, in which we examined the effects of
      stem length, loop sequence and insertion of mutation(s) and/or bulges in the stem
      sequence on silencing effects and on the stability of the vectors. RESULTS: As a
      result of the comparative analysis, we determined the following optimized siRNA
      expression system: U6 promoter-driven hairpin-type dsRNA with 21-nt stem length,
      three to four mutations in the sense strand only, and the optimized 9-nt loop
      sequence, derived from microRNA. Moreover, we demonstrate that the siRNA
      expression system with a tetracycline-regulated U6 promoter(s) could have the
      potential to control RNAi in cells, and that the HIV vector-mediated transfer of
      an siRNA-expression cassette into cells resulted in efficient silencing of a
      target gene at a multiplicity of infection as low as five. CONCLUSION: The
      mutated hairpin siRNAs and their genetically stable coding vectors could be very
      useful for gene knockdown experiments, and could further benefit gene therapy
      using RNAi.

PMID- 15241779
TI  - Factors affecting retrovirus-mediated gene transfer to human CD34+ cells.
AB  - BACKGROUND: Retrovirus-mediated gene transfer is a useful technology in studying
      the biology of hematopoietic stem cells (HSCs) as well as in developing gene
      therapy products for a variety of human diseases. One of the most important
      factors determining the success of these studies is the number of HSCs receiving
      the gene of interest. METHODS: We tested various parameters for their influences
      on gene transfer efficiency to CD34+ cells derived from bone marrow. Based on a
      literature survey, three medium formulations of CD34+ cells have been compared
      for their effects on gene delivery efficiency and differentiation of them. We
      also tested whether FBS, used in the medium formulation, could be replaced with
      human serum or synthetic material. RESULTS: Formulation A, consisting of stem
      cell factor, Flt-3 ligand, thrombopoietin, and IL-3, provided optimum results in
      that it maintained the highest percentage of CD34+ cells during the culture as
      well as produced the highest gene delivery efficiency. It was found that the
      synthetic serum substitute containing bovine serum albumin, insulin and human
      transferrin could replace the fetal bovine serum present in the original
      formulation A without compromising gene transfer efficiency. When the
      transduction procedure was repeated three times, the gene could be delivered in
      up to 60% of the cell population. Gene delivery efficiency was comparable between
      CD34+ cells derived from bone marrow and mobilized peripheral blood. CONCLUSIONS:
      Our data could be useful in designing a procedure for stem cell gene therapy and
      providing a basis for further improving the conditions for gene transfer to
      various HSCs.

PMID- 15241780
TI  - Adenoviral gene transfer to the neonatal rat pulmonary circulation.
AB  - BACKGROUND: Gene delivery to the pulmonary circulation has been studied in adult
      animals, but has not been extensively investigated in neonates. METHODS: We
      tested the ability of recombinant, replication-defective adenovirus to transduce
      the pulmonary circulation when delivered by percutaneous ventricular puncture.
      Five-day-old rat pups were injected with 10(7) to 10(10) particles (approximately
      10(5) to 10(8) pfu) in 30 micro l total volume. RESULTS: Using RT-PCR, we
      detected transgene expression in both lung and liver at all dosages. However,
      whereas only 1/6 pups injected with 10(7) particles had detectable expression,
      8/9 pups in the two highest dose groups had detectable expression. In the highest
      dose group expression was approximately 5-fold greater in lung than liver, though
      in the lower dose groups no difference between lung and liver was found.
      Expression decreased by only 25% from day 4 through the last time point at day 28
      in lung, whereas liver expression was undetectable in 7 of 9 samples on day 28.
      Histopathological examination demonstrated expression both within the media of
      large arteries and in small, peripheral arteries and capillaries, with a
      concentration of expression in the most distal areas of both the lungs and liver.
      No evidence of inflammation was seen. CONCLUSIONS: We conclude that the neonatal
      pulmonary circulation can be effectively transduced using systemic adenoviral
      vector injection, has more sustained expression than liver, and may be a target
      for therapeutic gene delivery.

PMID- 15241781
TI  - Neuropathological consequences of delivering an adenoviral vector in the rat
      brain.
AB  - BACKGROUND: Adenoviruses have many advantages as vehicles for gene delivery to
      the central nervous system (CNS) and retrograde transport of vectors to axonally
      linked sites has been postulated as a method for targeting neurons in remote
      brain regions. To investigate optimisation of this we injected different doses of
      vector and have documented the neuropathological side effects. METHODS:
      Increasing doses of a first-generation adenoviral vector, expressing the lacZ
      gene, were inoculated in the rat striatum and beta-galactosidase expression was
      examined at the primary and secondary sites. Subsequently, at the highest dose of
      vector, transgene expression, the inflammatory response, tyrosine hydroxylase
      (TH) expression and the rotational behaviour of animals were studied over time.
      RESULTS: When a high dose of an adenoviral vector was delivered to the rat
      striatum, high levels of transgene expression were seen at 5 days in the
      injection site and in the substantia nigra. Smaller doses gave lower levels of
      expression with little expression detectable in the substantia nigra. At later
      time points, with the high dose, a marked reduction in transgene expression was
      detected and was accompanied by cytopathic damage, a strong inflammatory response
      and animal weight loss. This was associated with depletion in TH levels and
      abnormal motor behaviour in animals. CONCLUSIONS: Neuropathological damage in the
      dopaminergic system, caused by high doses of adenoviral vectors, has not
      previously been documented. To minimise damage and prolong transgene expression,
      it is important that the dose of vectors to be delivered is carefully optimised.

PMID- 15241782
TI  - Short-term culture of myeloid leukemic cells allows efficient transduction by
      adenoviral vectors.
AB  - BACKGROUND: Ex vivo gene therapy of acute myeloid leukemia (AML) requires
      efficient transduction of leukemic cells. Recombinant adenovirus has been
      reported to be a poorly efficient vector in leukemic cells. We investigated
      leukemic cell culture as a possible method of improving the efficacy of this
      vector. METHODS: Leukemic cell lines and primary cultured AML cells were
      incubated with adenoviral vectors carrying GFP, LacZ, or IL-12 cDNA. Transduction
      efficiency was evaluated by measuring adenoviral genome copy number and transgene
      expression in leukemic cells. The expression of the coxsackie/adenovirus receptor
      (CAR), CD29, CD49e, and CD51/61 was measured, as was the effect of blocking
      integrin on adenoviral transduction. RESULTS: Increasing the multiplicity of
      infection (MOI) to 300 plaque-forming units per cell enhanced transduction of
      leukemic cell lines and to a lesser degree of AML cells. Analysis of adenoviral
      genome copy per cell showed only a partial correlation between gene transfer
      efficiency and transgene expression. Culture of AML cells for 3 days prior to
      adenoviral transduction increased both adenoviral copy number per cell and the
      percentage of transgene-expressing cells. CD29, CD49e, and CD51/61 but not CAR
      expression increased in cultured AML cells between days 0 and 3 and integrin
      blocking experiments showed inhibition of transduction in two of four AML samples
      tested. CONCLUSIONS: Efficient ex vivo gene transfer in primary cultured AML
      cells can be achieved by short-term culture of leukemic cells prior to gene
      transfer with adenoviral vectors at a high MOI. This effect appears to be at
      least partially mediated by enhanced integrin expression.

PMID- 15241783
TI  - An engineered EBV vector expressing human factor VIII and von Willebrand factor
      in cultured B-cells.
AB  - BACKGROUND: Hemophilia A is a congenital disorder caused by a deficiency of the
      blood-clotting factor VIII (FVIII) and is an attractive candidate for gene
      therapy. Most of the studies have only explored the potential of hepatocytes and
      muscle cells as the targets for gene transfer. Attempts to transfer the genes
      into hematopoietic cells have so far been mostly unsuccessful due to inefficiency
      of most viral vectors to transduce these cells and the supposed inability of the
      cells to express FVIII. METHODS: We demonstrate the generation of an engineered
      Epstein-Barr virus (EBV) vector with a BAC backbone that has the unique capacity
      to carry either the full-length FVIII cDNA or its B-domain-deleted form; a
      modified version of the vector that carries B-domain-deleted FVIII along with the
      von Willebrand factor (vWF) cDNA or the reporter gene DsRed2 was also used. All
      these vectors have been safety modified with viral thymidine kinase cDNA to
      transduce human B-cells in culture. RESULTS: Low-level expression of FVIII in the
      order of 5-8 ng FVIIIC/ml were observed in the cells stably transduced with full
      length FVIII, while cells with the B-domain-deleted version expressed 8-16 ng
      FVIIIC/ml. Expression of vWF and B-domain-deleted FVIII resulted in a moderate
      expression of 18-30 ng FVIIIC/ml. Long-term expression for 12-16 weeks was
      observed in these cells regardless of selection pressure. CONCLUSIONS: These
      results support the development of an episomal engineered EBV vector for
      treatment of hemophilia A using the hematopoietic cells as a target for providing
      immediate secretion of functionally active product in the circulating
      bloodstream.

PMID- 15241784
TI  - A model for non-viral gene delivery: through syndecan adhesion molecules and
      powered by actin.
AB  - BACKGROUND: Cell transfection requires cationic DNA complexes and heparan sulfate
      proteoglycans (HSPGs) at the cell surface. Syndecans are transmembrane HSPGs that
      are ubiquitously expressed on adherent cells. Their polyanionic heparan sulfate
      moieties are bound at the distal end of their ectodomain, thus facilitating
      interaction with large cationic particles. METHODS: We propose a model for cell
      entry involving syndecans as receptors for the DNA complexes by comparing
      transfection with bacteria uptake and using drug inhibition experiments along
      with confocal microscopy. RESULTS: When combined with results from the
      literature, our data suggest the following sequence of events: after initial
      particle binding, gradual electrostatic zippering of the plasma membrane onto the
      particle is sustained by lateral diffusion of syndecan molecules that cluster
      into cholesterol-rich rafts. Clustering in turn triggers PKC activity and linker
      protein-mediated actin binding to the cytoplasmic tail of the syndecans.
      Resulting tension fibers and a growing network of cortical actin may then pull
      the particle into the cell. CONCLUSIONS: Diversion of integrin- and syndecan
      mediated cell adhesion processes for particle engulfment appears to be widely
      exploited by animals (chylomicrons), by pathogens (bacteria, viruses) and, as
      suggested here, by non-viral vectors.

PMID- 15241785
TI  - Synergistic anti-tumor effect of glycosylphosphatidylinositol-anchored IL-2 and
      IL-12.
AB  - BACKGROUND: Preclinical and clinical studies have demonstrated that interleukin 2
      (IL-2), interleukin 12 (IL-12), and some other cytokines, play important roles in
      activating host immune responses against tumor growth. However, severe side
      effects caused by systemic high-dose administration of these cytokines limit
      their clinical application. In our previous study, local high doses of IL-2 were
      achieved by a GPI-anchoring technology; therefore, it will be interesting to know
      if this technology works for other cytokines. METHODS: A fusion gene containing
      murine IL-12 and the glycosylphosphatidylinositol (GPI) anchor signal sequence
      was generated and transfected into the murine melanoma tumor cell line B16F0
      either alone or together with a vector encoding GPI-anchored IL-2. The GPI
      anchored cytokine expression of the selected stable clones was assayed in vitro
      by ELISA and their anti-tumor effects were analyzed in vivo by tumor lymphocyte
      infiltration and tumor growth studies. RESULTS: GPI-anchored IL-12 was
      successfully expressed on the cell surface as indicated by FACS analysis and IL
      12 ELISA assay. The GPI-anchored IL-12 enhanced lymphocyte infiltration and
      significantly inhibited tumor growth. More importantly, when GPI-anchored IL-12
      and GPI-anchored IL-2 were co-delivered, a synergistic anti-tumor effect was
      observed in both subcutaneous and intravenous tumor models. CONCLUSIONS: GPI
      anchorage of cytokines represents a new approach to locally deliver high doses of
      cytokines without the severe adverse effects normally accompanied with systematic
      high-dose administration of these cytokines.

PMID- 15241786
TI  - Encapsulated transgene cells attenuate hypertension, cardiac hypertrophy and
      enhance renal function in Goldblatt hypertensive rats.
AB  - BACKGROUND: The success of any gene-therapy approach depends on the survival of
      the genetically engineered cells that are implanted in the patient to deliver the
      therapeutic product. Immunoisolation of nonautologous cells within a microcapsule
      is a unique approach for gene therapy. METHODS: We employed an immunoisolation
      device that protects nonautologous cells from destruction, to implant human
      atrial natriuretic peptide (hANP)-producing Chinese hamster ovary (CHO) cells in
      two-kidney, one-clip (2K1C) hypertensive rats. CHO cells transfected with the
      plasmid CMV-cANP were encapsulated in biocompatible polycaprolactone (PCL)
      capsules, and then the PCL capsules were implanted into 2K1C hypertensive rats
      intraperitoneally. RESULTS: The implantation of encapsulated hANP-producing cells
      caused a significant delay of blood pressure (BP) increase 2 weeks post
      implantation and the effect lasted for more than 5 months. The implantation of
      encapsulated hANP-producing cells also caused significant increases in renal
      blood flow (RBF), glomerular filtration rate (GFR), sodium output, urine
      excretion, and urinary cGMP levels. These beneficial effects were reflected
      morphologically by an attenuation of the glomerular sclerotic lesions, reduction
      in cardiomyocyte size, tubular injury and renal arterial thickening.
      Immunoreactive hANP can be detected in the blood of 2K1C rats after implantation
      of the PCL capsules containing hANP-producing cells. CONCLUSIONS: This study
      demonstrates the usefulness of encapsulated ANP gene transfected cells as a new
      tool for ANP gene delivery in studying renovascular hypertension and
      cardiovascular diseases. Thus, our results may have important implications for
      clinical use of transgene cells as therapeutic agents in the treatment of
      cardiovascular diseases.

PMID- 15241787
TI  - Immunotherapy with autologous tumor cells engineered to secrete Tag7/PGRP, an
      innate immunity recognition molecule.
AB  - BACKGROUND: Recent studies indicate that the innate component of immune defense
      plays an important role in the establishment of antigen-specific immune response.
      We have previously isolated a novel mouse gene tag7/PGRP that was shown to be
      involved in the innate component of the immune system, and its insect homologue
      is an upstream mediator of Toll signaling in Drosophila. METHODS: Transiently or
      stably genetically modified mouse tumor cell lines expressing Tag7 were used.
      Tumor growth rate and animal survival were analyzed. Possible effector cells
      involved in tumor suppression were detected immunohistochemically. RESULTS:
      Transfection of mammary gland adenocarcinoma cells with the tag7 cDNA did not
      alter their growth rate in vitro but diminished their tumorogenicity in vivo in
      syngeneic and immunodeficient animals. Increased incidence of apoptosis was
      registered in the modified tumors. Transient expression of Tag7 by mouse melanoma
      M3 cells elicited protective immunity against parental tumor cells.
      Immunohistochemical analysis revealed that tumors after immunization with the
      genetically modified cells were infiltrated with Mac1(+) cells, B220(+) cells,
      and NK cells. Using nude mice we observed rejection of modified cells, but did
      not detect memory formation. CONCLUSIONS: We can conclude that secretion of the
      Tag7 protein by genetically modified cells can induce mobilization of antigen
      presenting cells and innate effectors. Memory mechanisms are mediated by T cell
      response. For the first time our results demonstrate that local secretion of Tag7
      the molecule involved in innate immunity-may play an important role in the
      induction of effective antitumor response in mice.

PMID- 15241788
TI  - In vivo gene electrotransfer into skeletal muscle: effects of plasmid DNA on the
      occurrence and extent of muscle damage.
AB  - BACKGROUND: Understanding the mechanisms underlying gene electrotransfer muscle
      damage can help to design more effective gene electrotransfer strategies for
      physiological and therapeutical applications. The present study investigates the
      factors involved in gene electrotransfer associated muscle damage. METHODS:
      Histochemical analyses were used to determine the extent of transfection
      efficiency and muscle damage in the Tibialis anterior muscles of Sprague-Dawley
      male rats after gene electrotransfer. RESULTS: Five days after gene
      electrotransfer, features of muscle degeneration and regeneration were
      consistently observed, thus limiting the extent of transfection efficiency. Signs
      of muscle degeneration/regeneration were no longer evident 21 days after gene
      electrotransfer except for the presence of central myonuclei. Neither the
      application of electrical pulses per se nor the extracellular presence of plasmid
      DNA per se contributed significantly to muscle damage (2.9 +/- 1.0 and 2.1 +/-
      0.7% of the whole muscle cross-sectional area, respectively). Gene
      electrotransfer of a plasmid DNA, which does not support gene expression,
      increased significantly muscle damage (8.7 +/- 1.2%). When plasmid DNA expression
      was permitted (gene electrotransfer of pCMV-beta-galactosidase), muscle damage
      was further increased to 19.7 +/- 4.5%. Optimization of cumulated pulse duration
      and current intensity dramatically reduced gene electrotransfer associated muscle
      damage. Finally, mathematical modeling of gene electrotransfer associated muscle
      damage as a function of the number of electrons delivered to the tissue indicated
      that pulse length critically determined the extent of muscle damage. CONCLUSION:
      Our data suggest that neither the extracellular presence of plasmid DNA per se
      nor the application of electric pulses per se contributes significantly to muscle
      damage. Gene electrotransfer associated muscle damage mainly arises from the
      intracellular presence and expression of plasmid DNA.

PMID- 15241789
TI  - Second-generation tetracycline-regulatable promoter: repositioned tet operator
      elements optimize transactivator synergy while shorter minimal promoter offers
      tight basal leakiness.
AB  - BACKGROUND: The tetracycline-regulatable system is one of the most valuable tools
      for controlling gene expression. In its current form, however, the system is less
      than ideal for in vivo or gene therapy uses due to difficulties in set-up
      procedures, high basal leakiness, and unpredictable delivery and efficiency.
      METHODS: To address these issues, we have devised a second generation of
      tetracycline-regulated promoters (TREs). The second-generation TRE (SG-TRE)
      contains a shortened cytomegalovirus (CMV) minimal promoter together with eight
      tet operator sequences positioned in an optimized manner upstream of the TATA
      box. This construct displays far greater reduction in basal leakiness than
      maximal transgene expression. Conversely, maximal transgene expression is
      increased to a greater degree than basal leakiness by post-translational
      stabilization with bovine growth hormone poly A. RESULTS: In transient studies,
      the SG-TRE displays over 100 000-fold regulation efficiency in HeLa cells at 1:1
      ratio of transactivator to reporter plasmid in the Tet-Off system. This novel
      promoter achieves a regulation efficiency 500- to 1000-fold higher than that of
      the original TRE (P(hCMV*-1)) in HeLa cells by displaying undetectable levels of
      basal leakiness without compromised maximal expression. In other cell lines, the
      SG-TRE proves to be more efficient than the original P(hCMV*-1) in a cell
      dependent manner. Furthermore, the SG-TRE preserves its enhanced regulation
      efficiency and its reduced basal leakiness in the context of a single positive
      feedback regulatory vector that presents ease of delivery of the system for use
      in vivo. Finally, in vivo, the biological function of granulocyte-macrophage
      colony stimulating factor is tightly regulated in the context of SG-TRE delivered
      via adeno-associated viruses.

PMID- 15241791
TI  - CASRdb: calcium-sensing receptor locus-specific database for mutations causing
      familial (benign) hypocalciuric hypercalcemia, neonatal severe
      hyperparathyroidism, and autosomal dominant hypocalcemia.
AB  - Familial hypocalciuric hypercalcemia (FHH) is caused by heterozygous loss-of
      function mutations in the calcium-sensing receptor (CASR), in which the lifelong
      hypercalcemia is generally asymptomatic. Homozygous loss-of-function CASR
      mutations manifest as neonatal severe hyperparathyroidism (NSHPT), a rare
      disorder characterized by extreme hypercalcemia and the bony changes of
      hyperparathyroidism, which occur in infancy. Activating mutations in the CASR
      gene have been identified in several families with autosomal dominant
      hypocalcemia (ADH), autosomal dominant hypoparathyroidism, or hypocalcemic
      hypercalciuria. Individuals with ADH may have mild hypocalcemia and relatively
      few symptoms. However, in some cases seizures can occur, especially in younger
      patients, and these often happen during febrile episodes due to intercurrent
      infection. Thus far, 112 naturally-occurring mutations in the human CASR gene
      have been reported, of which 80 are unique and 32 are recurrent. To better
      understand the mutations causing defects in the CASR gene and to define specific
      regions relevant for ligand-receptor interaction and other receptor functions,
      the data on mutations were collected and the information was centralized in the
      CASRdb (www.casrdb.mcgill.ca), which is easily and quickly accessible by search
      engines for retrieval of specific information. The information can be searched by
      mutation, genotype-phenotype, clinical data, in vitro analyses, and authors of
      publications describing the mutations. CASRdb is regularly updated for new
      mutations and it also provides a mutation submission form to ensure up-to-date
      information. The home page of this database provides links to different web pages
      that are relevant to the CASR, as well as disease clinical pages, sequence of the
      CASR gene exons, and position of mutations in the CASR. The CASRdb will help
      researchers to better understand and analyze the mutations, and aid in structure
      function analyses.

PMID- 15241792
TI  - OrthoDisease: a database of human disease orthologs.
AB  - One of the greatest promises of genome sequencing projects is to further the
      understanding of human diseases and to develop new therapies. Model organism
      genomes have been sequenced in parallel to human genomes to provide effective
      tools for the investigation of human gene function. Many of their genes share a
      common ancestry and function with human genes, and this is particularly true for
      orthologous genes. Here we present OrthoDisease, a comprehensive database of
      model organism genes that are orthologous to human disease genes. OrthoDisease
      was constructed by applying the Inparanoid ortholog detection algorithm to
      disease genes derived from the Online Mendelian Inheritance in Man database
      (OMIM). Pairwise whole genome/proteome comparisons between Homo sapiens and six
      other organisms were performed to identify ortholog clusters. OMIM numbers were
      extracted from the OMIM Morbid Map and were converted to gene sequences using the
      Locuslink mim2loc and loc2acc tables. These were mapped to Inparanoid ortholog
      clusters using Blast. The number of ortholog clusters in OrthoDisease with each
      respective species is currently: M. musculus, 1,354; D. melanogaster, 724; C.
      elegans, 533; A. thaliana, 398; S. cerevisiae, 290; and E. coli, 153. The
      database is accessible online at http://orthodisease.cgb.ki.se, and can be
      searched with disease or protein names. The web interface presents all ortholog
      clusters that include a selected disease gene. A capability to download the
      entire dataset is also provided.

PMID- 15241793
TI  - The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping
      in nonmutated CFTR alleles.
AB  - Classic cystic fibrosis (CF) is caused by two loss-of-function mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene, whereas patients
      with nonclassic CF have at least one copy of a mutant gene that retains partial
      function of the CFTR protein. In addition, there are several other phenotypes
      associated with CFTR gene mutations, such as idiopathic chronic pancreatitis. In
      CFTR-associated disorders and in nonclassic CF, often only one CFTR mutation or
      no CFTR mutations can be detected. In this study, we screened 23 patients with
      CFTR-associated disorders for CFTR mutations by complete gene testing and
      quantitative transcript analysis. Mutations were found in 10 patients. In cells
      from respiratory epithelium, we detected aberrant splicing of CFTR mRNA in all
      investigated individuals. We observed a highly significant association between
      the presence of coding single-nucleotide polymorphisms (coding SNPs, or cSNPs)
      and increased skipping of exon 9 and 12. This association was found both in
      patients and in normal individuals carrying the same cSNPs. The cSNPs c.1540A>G,
      c.2694T>G, and c.4521G>A may have affected pre-mRNA splicing by changing
      regulatory sequence motifs of exonic splice enhancers, leading to lower amounts
      of normal transcripts. The analysis of CFTR exons indicated that less frequent
      and weak exonic splicing enhancer (ESE) motifs make exon 12 vulnerable to
      skipping. The number of splice variants in individuals with cSNPs was similar to
      previously reported values for the T5 allele, suggesting that cSNPs may enhance
      susceptibility to CFTR related diseases. In addition, cSNPs may be responsible
      for variation in the phenotypic expression of CFTR mutations. Quantitative
      approaches rather than conventional genomic analysis are required to interpret
      the role of cSNPs.

PMID- 15241794
TI  - Identification of the molecular defect in patients with peroxisomal mosaicism
      using a novel method involving culturing of cells at 40 degrees C: implications
      for other inborn errors of metabolism.
AB  - The peroxisome biogenesis disorders (PBDs), which comprise Zellweger syndrome
      (ZS), neonatal adrenoleukodystrophy, and infantile Refsum disease (IRD),
      represent a spectrum of disease severity, with ZS being the most severe, and IRD
      the least severe disorder. The PBDs are caused by mutations in one of the at
      least 12 different PEX genes encoding proteins involved in the biogenesis of
      peroxisomes. We report the biochemical characteristics and molecular basis of a
      subset of atypical PBD patients. These patients were characterized by abnormal
      peroxisomal plasma metabolites, but otherwise normal to very mildly abnormal
      peroxisomal parameters in cultured skin fibroblasts, including a mosaic catalase
      immunofluorescence pattern in fibroblasts. Since this latter feature made
      standard complementation analysis impossible, we developed a novel
      complementation technique in which fibroblasts were cultured at 40 degrees C,
      which exacerbates the defect in peroxisome biogenesis. Using this method, we were
      able to assign eight patients to complementation group 3 (CG3), followed by the
      identification of a single homozygous c.959C>T (p.S320F) mutation in their PEX12
      gene. We also investigated various peroxisomal biochemical parameters in
      fibroblasts at 30 degrees C, 37 degrees C, and 40 degrees C, and found that all
      parameters showed a temperature-dependent behavior. The principle of culturing
      cells at elevated temperatures to exacerbate the defect in peroxisome biogenesis,
      and thereby preventing certain mutations from being missed, may well have a much
      wider applicability for a range of different inborn errors of metabolism.

PMID- 15241795
TI  - Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of
      classical Marfan syndrome.
AB  - In order to estimate the contribution of mutations at the fibrillin-1 locus
      (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic
      differences between patients with an FBN1 mutation vs. without, a comprehensive
      molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the
      clinical diagnosis of MFS according to the Ghent nosology was performed. The
      initial mutation screening by CSGE/SSCP allowed identification of an FBN1
      mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11
      mutation-negative patients, while in nine others, DHPLC was used. This allowed
      identification of seven and five additional mutations, respectively. Southern
      blot analysis revealed an abnormal hybridization pattern in one more patient. A
      total of 23 out of the 85 mutations identified here are reported for the first
      time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs.
      premature termination mutations revealed significant differences in ocular and
      skeletal involvement. The phenotype of the eight patients without proven FBN1
      mutation did not differ from the others with respect to the presence of major
      cardiac, ocular, and skeletal manifestations or positive familial history. Most
      likely, a portion of FBN1-mutations remains undetected because of technical
      limitations. In conclusion, the involvement of the FBN1-gene could be
      demonstrated in at least 91% of all MFS patients (85/93), which strongly suggests
      that this gene is the predominant, if not the sole, locus for MFS.

PMID- 15241796
TI  - Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing
      loss in osteogenesis imperfecta patients.
AB  - Osteogenesis imperfecta (OI) is caused by mutations in COL1A1 and COL1A2 that
      code for the alpha1 and alpha2 chains of type I collagen. Phenotypes correlate
      with the mutation types in that COL1A1 null mutations lead to OI type I, and
      structural mutations in alpha1(I) or alpha2(I) lead to more severe OI types (II
      IV). However, correlative analysis between mutation types and OI associated
      hearing loss has not been previously performed. A total of 54 Finnish OI patients
      with previously diagnosed hearing loss or age 35 or more years were analyzed here
      for mutations in COL1A1 or COL1A2. Altogether 49 mutations were identified, of
      which 41 were novel. The 49 mutations represented the molecular genetic
      background of 41.1% of the Finnish OI population. A total of 38 mutations were in
      COL1A1 and 11 were in COL1A2. Of these, 16 were glycine substitutions and 16 were
      splicing mutations in alpha1(I) or alpha2(I). In addition, 17 null allele
      mutations were detected in COL1A1. A total of 32 patients (65.3%) with a mutation
      had hearing loss. That is slightly more than in our previous population study on
      Finnish adults with OI (57.9%). The association between the mutation types and OI
      type was statistically evident. Patients with COL1A1 mutations more frequently
      had blue scleras than those with COL1A2 mutations. In addition, patients with
      COL1A2 mutations tended to be shorter than those with COL1A1 mutations. However,
      no correlation was found between the mutated gene or mutation type and hearing
      pattern. These results suggest that the basis of hearing loss in OI is complex,
      and it is a result of multifactorial, still unknown genetic effects.

PMID- 15241797
TI  - A gel-free SNP genotyping method: bioluminometric assay coupled with modified
      primer extension reactions (BAMPER) directly from double-stranded PCR products.
AB  - Inexpensive, high-throughput genotyping methods are needed for analyzing human
      genetic variations. We have successfully applied the regular bioluminometric
      assay coupled with modified primer extension reactions (BAMPER) method to single
      nucleotide polymorphism (SNP) typing as well as the allele frequency
      determination for various SNPs. This method includes the production of single
      strand target DNA from a genome and a primer extension reaction coupled with
      inorganic pyrophosphate (PPi) detection by a bioluminometric assay. It is an
      efficient way to get accurate allele frequencies for various SNPs, while single
      strand DNA preparation is labor intensive. The procedure can be simplified in the
      typing of SNPs. We demonstrate that a modified BAMPER method in which we need not
      prepare a single-strand DNA can be carried out in one tube. A PCR product is
      directly used as a template for SNP typing in the new BAMPER method. Generally,
      tremendous amounts of PPi are produced in a PCR process, as well as many residual
      dNTPs, and residual PCR primers remain in the PCR products, which cause a large
      background signal in a bioluminometric assay. Here, shrimp alkaline phosphatase
      (SAP) and E. coli exonuclease I were used to degrade these components prior to
      BAMPER detection. The specific primer extension reactions in BAMPER were carried
      out under thermocycle conditions. The primers were extended to produce large
      amounts of PPi only when their bases at 3'-termini were complementary to the
      target. The extension products, PPis, were converted to ATP to be analyzed using
      the luciferin-luciferase detection system. We successfully demonstrated that PCR
      products can be directly genotyped by BAMPER in one tube for SNPs with various GC
      contents. As all reactions can be carried out in a single tube, the method will
      be useful for realizing a fully automated genotyping system.

PMID- 15241798
TI  - Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe
      amplification (MLPA) with rapid DNA preparations: comparison with the interphase
      FISH method.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with
      liability to pressure palsies (HNPP) are the two most common peripheral
      neuropathies, with incidences of about 1 in 2,500. Several techniques can be used
      to detect the typical 1.5-Mb duplication or deletion associated with these
      respective conditions, but none combines simplicity with high sensitivity. MLPA
      is a new technique for measuring sequence dosage. We have assessed its
      performance for the detection of the specific 1.5-Mb duplication/deletion by
      prospectively testing 50 patients referred with differential diagnoses of CMT or
      HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within
      the CMT1A/HNPP region. We have compared the results with our existing
      fluorescence in situ hybridization (FISH) assay, which was performed in parallel.
      There was concordance of results for 49 patients. Of note, one patient showed an
      intermediate multiplex ligation-dependent probe amplification (MLPA) result with
      an abnormal FISH result, which is consistent with mosaicism. The assay works
      equally well with either purified DNA or rapid DNA preparations made by direct
      cell lysis. The use of the latter significantly reduces the cost of the assay.
      MLPA is a sensitive, specific, robust, and cost-effective technique suitable for
      fast, high-throughput testing and offers distinct advantages over other testing
      methods.

PMID- 15241799
TI  - Real-time quantitative PCR as a routine method for screening large rearrangements
      in Rett syndrome: Report of one case of MECP2 deletion and one case of MECP2
      duplication.
AB  - Mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are found in
      70-80% of cases of classical Rett syndrome (RTT) and in about 50% of cases of
      preserved speech variant (PSV). This high percentage of MECP2 mutations,
      especially in classical RTT cases, suggests that another major RTT locus is
      unlikely. Missed mutations may be due to the limited sensitivity of the
      methodology used for mutation scanning and/or the presence of intronic mutations.
      In a double-copy gene, such as MECP2 in females, current methodologies (e.g.,
      DGGE, SSCP, DHPLC, direct sequencing) are prone to miss gross rearrangements.
      Three previous reports during 2001-2003 have shown the presence of large
      deletions in a fraction of MECP2-negative classical RTT patients. We developed a
      reliable, single tube, quantitative PCR assay for rapid determination of MECP2
      gene dosage. This method involves a multiplex reaction using a FAM labeled TaqMan
      probe with a TAMRA quencher derived from MECP2 exon 4 and two primers derived
      from the same exon and RNAaseP as an internal reference. The copy number of the
      MECP2 gene was determined by the comparative threshold cycle method (ddCt). Each
      sample was run in quadruplicate. We validated this assay through the analysis of
      30 healthy controls (15 female and 15 male) and we then applied this method to
      eight classical RTT and six PSV patients, all negative for MECP2 mutations. We
      identified gross rearrangements in two patients: a deletion in a classical RTT
      patient and a duplication in a PSV patient. Our results confirm that a fraction
      of MECP2-negative RTT cases have MECP2 gross rearrangements and we propose real
      time quantitative PCR as a simple and reliable method for routine screening of
      MECP2 in addition to DHPLC analysis.

PMID- 15241800
TI  - Bayesian approach to discovering pathogenic SNPs in conserved protein domains.
AB  - The success rate of association studies can be improved by selecting better
      genetic markers for genotyping or by providing better leads for identifying
      pathogenic single nucleotide polymorphisms (SNPs) in the regions of linkage
      disequilibrium with positive disease associations. We have developed a novel
      algorithm to predict pathogenic single amino acid changes, either nonsynonymous
      SNPs (nsSNPs) or missense mutations, in conserved protein domains. Using a
      Bayesian framework, we found that the probability of a microbial missense
      mutation causing a significant change in phenotype depended on how much
      difference it made in several phylogenetic, biochemical, and structural features
      related to the single amino acid substitution. We tested our model on pathogenic
      allelic variants (missense mutations or nsSNPs) included in OMIM, and on the
      other nsSNPs in the same genes (from dbSNP) as the nonpathogenic variants. As a
      result, our model predicted pathogenic variants with a 10% false-positive rate.
      The high specificity of our prediction algorithm should make it valuable in
      genetic association studies aimed at identifying pathogenic SNPs.

PMID- 15241801
TI  - USH2A mutation analysis in 70 Dutch families with Usher syndrome type II.
AB  - Usher syndrome type II (USH2) is characterised by moderate to severe high
      frequency hearing impairment, progressive visual loss due to retinitis pigmentosa
      and intact vestibular responses. Three loci are known for USH2, however, only the
      gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was
      performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of
      which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T
      (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of
      the prevalence of USH2a in the Dutch USH2 population were made. Mutations were
      identified in 62% of the families. In 28% both mutated alleles were identified,
      whereas in 34% the mutation in only one allele was found. It is estimated that
      about 28% of the Dutch USH2 families have a different causative gene. Analysis of
      deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral
      mutation, occurring in 16% of the alleles.

PMID- 15241802
TI  - Characterization of three myotonia-associated mutations of the CLCN1 chloride
      channel gene via heterologous expression.
AB  - Two novel mutations of the human CLCN1 chloride channel gene, c.592C>G (p.L198V)
      and c.2255A>G (p.K752R), are described, occurring coincidentally in the one
      myotonic patient. These individual mutations and a construct with both mutations
      in the one cDNA were transcribed and expressed in Xenopus oocytes where channel
      gating parameters were extracted from chloride currents recorded under voltage
      clamp. We found that the p.L198V mutation has its major effects on the common (or
      slow) gate of the chloride channel, as do other dominant ClC-1 mutations, and may
      therefore be causative of the patient's symptoms (when co-expressed with wild
      type human ClC-1, the p.L198V mutation exerts a dominant negative effect on
      common gating) but the p.K752R mutation appears to be innocuous and may be a
      benign polymorphism. A third mutant, the recently described c.2795C>T (p.P932L),
      was expressed in HEK 293 cells. Despite the severity of the disease associated
      with this mutation, chloride currents in cells expressing p.P932L were not
      significantly different from those of cells expressing wild-type ClC-1.

PMID- 15241803
TI  - Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie
      Tooth neuropathy patients.
AB  - We examined CMT1A duplication of 17p11.2-p12, mutations of PMP22, MPZ (P0), GJB1
      (Cx32), EGR2 and NEFL genes in 57 Korean families with patients diagnosed as
      having Charcot-Marie-Tooth (CMT) disease. The CMT1A duplication was present in
      53.6% of 28 CMT type 1 patients. In the 42 CMT families without CMT1A
      duplication, 10 pathogenic mutations were found in 9 families. The 10 mutations
      were not detected in 105 healthy controls. Seven mutations (c.318delT
      (p.Ala106fs) in PMP22, c.352G>A (p.Asp118Asn), c.449-1G>T (3'-splice site),
      c.706A>G (p.Lys236Glu) in MPZ, c.407T>C (p.Val136Ala)[corrected], c.502T>C
      (p.Cys168Arg) in GJB1, and c.1001T>C (p.Leu334Pro) in NEFL) were determined to be
      novel. The mutation frequencies of PMP22 and MPZ were similar to those found in
      several European populations, however, it appeared that mutations in GJB1 are
      less frequent in East Asian CMT patients than in Eur opean patients. We described
      the identified mutations and phenotype-genotype correlations based on nerve
      conduction studies.

PMID- 15241804
TI  - Sjogren-Larsson syndrome: seven novel mutations in the fatty aldehyde
      dehydrogenase gene ALDH3A2.
AB  - Sjogren-Larsson syndrome (SLS) is an inherited neurocutaneous disease caused by
      mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase
      (FALDH), an enzyme involved in lipid metabolism. We performed mutation analysis
      in probands or fetuses from 13 unrelated SLS families and identified seven novel
      ALDH3A2 mutations. Two mutations involved an insertion or deletion of a single
      guanine nucleotide at the same position in exon 9: c.1223delG and
      c.1223_1224insG. A 66-bp duplication in exon 2 probably arose from unequal
      crossing over within a mispaired 10-bp sequence that is normally repeated within
      the exon. Based on RT-PCR of fibroblast RNA, the c.1107+2T>G donor splice-site
      mutation in intron 7 produced two mRNA transcripts, one skipping exon 7 and the
      other skipping exons 6-8. Expression of the c.1139G>A mutation in exon 8, which
      is predicted to cause an amino acid substitution (Ser380Asn) in an evolutionarily
      conserved region of the FALDH catalytic domain, resulted in a protein with
      profoundly reduced enzymatic activity. By analyzing single nucleotide
      polymorphisms within the ALDH3A2 gene, we detected four different haplotypes
      among the new mutant alleles. These results demonstrate a rich diversity of
      mutations and haplotype associations in SLS.

PMID- 15241805
TI  - Acid sphingomyelinase: identification of nine novel mutations among Italian
      Niemann Pick type B patients and characterization of in vivo functional in-frame
      start codon.
AB  - Niemann Pick disease (NPD) is an autosomal recessive disorder due to the deficit
      of lysosomal acid sphingomyelinase, which results in intracellular accumulation
      of sphingomyelin. In the present work we studied 18 patients with NPD type B,
      including five individuals who presented an intermediate phenotype characterised
      by different levels of neurological involvement. We identified nine novel
      mutations in the SMPD1 gene including six single base changes c.2T>G, c.96G>A,
      c.308T>C, c.674T>C, c.732G>C, c.841G>A (p.M1_W32del, p.W32X, p.L103P, p.L225P,
      p.W244C, p.A281T) and three frameshift mutations c.100delC, c.565dupC, c.575dupC
      (p.G34fsX42, p.P189fsX1 and p.P192fsX14). The novel c.2T>G (p.M1_W32del) mutation
      inactivates the first in-frame translation start site of the SMPD1 gene and in
      the homozygous status causes NPD type B indicating that in'vivo translation of
      wild type SMPD1 initiates from the first in-frame ATG. Moreover, the new c.96G>A
      (p.W32X) introduces a premature stop codon before the second in-frame ATG. As a
      consequence of either c.2T>G (p.M1_W32del) or c.96G>A (p.W32X), impaired
      translation from the first in-frame ATG results in a mild NPD-B phenotype instead
      of the severe phenotype expected for a complete deficiency of the enzyme,
      suggesting that when the first ATG is not functional, the second initiation codon
      (ATG33) still produces a fairly functional sphingomyelinase. Analysis of the
      patients'clinical and molecular data demonstrated that all five patients with the
      intermediate phenotype carried at least one severe mutation. No association
      between the onset of pulmonary symptoms and genotype was observed. Finally, the
      presence of c.96G>A (p.W32X), the most frequent allele among Italian NPD type B
      population, and c.1799G>C (p.R600P) as compound heterozygotes in association with
      severe mutations suggested a beneficial effect for both mutations.

PMID- 15241806
TI  - Molecular characterization of familial hypercholesterolemia in Spain:
      identification of 39 novel and 77 recurrent mutations in LDLR.
AB  - Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial
      hypercholesterolemia (FH), an autosomal dominant inherited disorder associated
      with an increased risk of premature atherosclerosis. The aim of this study was to
      characterize the LDLR mutations in a group of 476 apparently non-related Spanish
      FH patients. The promoter region and the 18 exons with their flanking intron
      sequences of the LDLR gene were screened by PCR-SSCP analysis and DNA sequencing.
      In addition, we tested for the presence of the mutation p.R3500Q in the gene
      coding for apolipoprotein B-100 (apo B-100). We found 77 mutations previously
      described, and 39 novel mutations affecting the LDLR gene: 8 missense, 5
      nonsense, 15 frameshift, 5 splicing, 4 in frame, one nucleotide change in the non
      coding sequence of exon 1, and one silent variant. We have identified al least
      one of these LDLR gene mutations in 329 subjects (69%). Four patients were
      homozygous, 4 patients were compound heterozygous, 48 patients were found to
      carry two different sequence variants in the same allele and 4 patients carried
      three different sequence variants in the same allele. Additionally, 4 subjects
      were carriers of the p.R3500Q mutation in the apo B gene. All of these findings
      indicate that there is a broad spectrum of mutations and sequence variants in the
      LDLR gene causing FH in Spain.

PMID- 15241807
TI  - Mucopolysaccharidosis IVA (Morquio A): identification of novel common mutations
      in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene in Italian
      patients.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder caused by the
      deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Mutation
      screening of the GALNS gene was performed by RT-PCR with one amplicon and direct
      sequence analyses using cDNA samples from 15 Italian MPS IVA patients. Each
      mutation was confirmed at the genomic level. In this study, 13 different gene
      mutations with four common mutations (over 10% of mutant alleles) were identified
      in 12 severe and three milder (attenuated) MPS IVA patients. The gene alterations
      in 12 out of 13 were found to be point mutations and only one mutation was
      deletion. Ten of 13 mutations were novel. The c.1070C>T (p.Pro357Leu) mutation
      coexisted with c.1156C>T (p.Arg386Cys) mutation on the same allele. Together they
      accounted for 100% of the 30 disease alleles of the patients investigated. Four
      common mutations accounted for 70% of mutant alleles investigated. Urine keratan
      sulfate (KS) concentrations were elevated in all patients investigated. These
      data provide further evidence for extensive allelic heterogeneity and importance
      of relation among genotype, phenotype, and urine KS excretion as a biomarker in
      MPS IVA.

PMID- 15241808
TI  - Treating individuals with debilitating performance anxiety: An introduction.
AB  - Clinicians often see clients who have debilitating performance anxiety. They
      suffer from public speaking anxiety, stage fright, test-taking anxiety, and
      writing block. Their condition is so severe as to threaten to end their academic
      or professional career. Musicians and athletes also seek help because their
      anxiety before and during an event causes them to perform at a level well below
      their demonstrated capabilities. An estimated 2% of the U.S. population is
      afflicted by debilitating performance anxiety. Effective treatments are now
      available. This article reviews those behavioral, cognitive, and technological
      therapies that have shown great promise for treating individuals who have
      debilitating performance anxiety and introduces this issue of the Journal of
      Clinical Psychology: In Session devoted to this topic.

PMID- 15241809
TI  - Cognitive therapy for performance anxiety.
AB  - We present and illustrate the major components of cognitive therapy for
      performance anxiety, focusing on the performance fears of a client treated with a
      protocol designed for social phobia. The basic supposition of cognitive theory is
      that a client's thoughts and beliefs about situations maintain distressing
      feelings, such as anxiety. Changing these beliefs involves detection and
      disputation of anxiety-provoking thoughts, as well as testing of these thoughts
      through exposure to feared situations. Through a process of identifying existing
      beliefs about performance situations and challenging these beliefs, clients can
      gain a more realistic and less anxiety-producing perspective on performance
      tasks. Specific techniques, along with common difficulties and potential
      solutions, are presented in a detailed case study.

PMID- 15241810
TI  - A self-applied, Internet-based intervention for fear of public speaking.
AB  - The aim of this article is to introduce, illustrate, and present effectiveness
      data on a new telepsychology program for the treatment of fear of public
      speaking. The Talk to Me program is an Internet-based self-applied intervention
      that has several components, including a diagnostic assessment, a structured
      treatment, and an outcome protocol that evaluates treatment efficacy in a
      continuous manner. We describe the characteristics of the program and present a
      case study. Results demonstrated a significant decrease in levels of fear and
      avoidance related to speaking in public.

PMID- 15241811
TI  - A multimodal behavioral approach to performance anxiety.
AB  - Cognitive-behavior therapy (CBT) stresses a trimodal assessment framework
      (affect, behavior, and cognition [ABC]), whereas the multimodal approach assesses
      seven discrete but interactive components--behavior, affect, sensation, imagery,
      cognition, interpersonal relationships, and drugs/biological factors (BASIC
      I.D.). Only complex or recalcitrant cases call for the entire seven-pronged range
      of multimodal interventions. Various case illustrations are offered as examples
      of how a clinician might proceed when confronted with problems that fall under
      the general heading of performance anxiety. The main example is of a violinist in
      a symphony orchestra whose career was in serious jeopardy because of his extreme
      fear of performing in public. He responded very well to a focused but elaborate
      desensitization procedure. The hierarchy that was eventually constructed
      contained many dimensions and subhierarchies featuring interlocking elements that
      evoked his anxiety. In addition to imaginal systematic desensitization, sessions
      were devoted to his actual performance in the clinical setting. As a homework
      assignment, he found it helpful to listen to a long-playing record of an actual
      rehearsal and to play along with the world-renowned orchestra and conductor. The
      subsequent disclosure by the client of an important sexual problem was dealt with
      concomitantly by using a fairly conventional counseling procedure. Therapy
      required 20 sessions over a 3-month period.

PMID- 15241812
TI  - Short term dynamic psychotherapy goes to Hollywood: the treatment of performance
      anxiety in cinema.
AB  - This article uses characters in popular films to demonstrate the theory and
      application of short term dynamic psychotherapy (STDP) in the treatment of
      performance anxiety. The reader is taught to identify affect phobias that are
      hypothesized to underlie performance anxiety. Similar in function to external
      phobias, affect phobias or internal phobias involve the avoidance of feelings
      (e.g., fear about feeling anger, shame about showing grief, pain about
      closeness), which thwarts adaptive responding and generates numerous behavioral
      problems. STDP treatment focuses on the restructuring of defenses, conflicted
      affects, and attachments. The resolution of the affect phobia requires systematic
      desensitization of affective responses (i.e., exposure and desensitization of
      underlying conflicted feelings). When patients learn to access adaptive forms of
      feelings, performance anxiety can often be resolved.

PMID- 15241813
TI  - Behavioral treatment of debilitating test anxiety among medical students.
AB  - This article presents and illustrates the behavioral treatment of medical
      students and physicians whose debilitating test anxiety was associated with their
      failure to pass the United States Medical Licensing Examination (USMLE) or a
      specialty board test. Seventy-two medical trainees were treated consecutively
      because of at least one failure to pass these professional examinations.
      Behavioral treatment focused on their anxiety, which resulted in the "dual
      deficits" of poor test preparation, poor test performance, or both. Treatment
      featured progressive muscle relaxation, systematic desensitization, the self
      control triad, behavioral rehearsal, and a psychoeducational component. Ninety
      three percent of the clients eventually passed the examination while in
      treatment. Pass rates for this group were substantially higher than the national
      average for repeat USMLE test takers. Limitations of this treatment method are
      that it seemed too elaborate for some medical trainees and was less effective
      with those who had difficulty evoking anxiety.

PMID- 15241814
TI  - Pharmacotherapy for performance anxiety disorders: occasionally useful but
      typically contraindicated.
AB  - Pharmacotherapy is an effective part of treatment for most anxiety disorders, but
      not for specific phobia or performance anxiety. In them it is contraindicated,
      because it interferes with the effectiveness of exposure therapies and the
      extinction of fear responses. Interference with exposure-extinction is a drug
      side effect that should rarely if ever be tolerated in treating them. This
      article reviews the many indications for pharmacotherapy in treating most anxiety
      disorders and contrasts its usefulness in treatment of anxiety disorders with its
      relatively rare usefulness in treating specific phobias and performance anxiety.
      In both the latter disorders, benzodiazepines interfere with exposure and
      generally are best avoided, although temporary use, with safeguards, can
      sometimes be helpful for a specific phobia. The recent discovery that D
      cycloserine (DCS) facilitates exposure and the extinction of anxiety offers
      promise that it could in the future be usefully and broadly employed to catalyze
      and enhance exposure therapies.

PMID- 15241815
TI  - Etiology and treatment of social anxiety: a commentary.
AB  - Substantial advances in our understanding of the etiology and treatment of
      performance anxiety have occurred during the past decade. It has become clear
      that the development of efficient and effective treatments cannot be divorced
      from knowledge of the specific form of psychopathology being treated and that
      treatments must be tailored to this psychopathology. After describing a current
      model of the etiology of performance anxiety and social phobia, this commentary
      notes the common factors present across the rich and diverse set of articles in
      this issue describing treatments from different approaches and different
      theoretical orientations. To the extent that these common factors are important
      mechanisms of action, it is possible that the future will introduce more unified
      and more effective, efficient, and theoretically informed treatment for
      performance anxiety as well as the potential for preventive techniques.

PMID- 15241816
TI  - Controversies in the management of advanced laryngeal squamous cell carcinoma.

PMID- 15241817
TI  - Establishing the multidisciplinary care of patients with cancer in the state of
      Delaware.
AB  - Delaware has the fifth highest cancer death rate in the U.S. As part of a
      comprehensive program to decrease the cancer mortality and incidence in the
      state, an infrastructure to establish the multidisciplinary care of patients with
      cancer was established. In May 2002, Christiana Care Health Services opened the
      Helen F. Graham Cancer Center to meet the specific need for coordinated and
      centralized comprehensive cancer care. This effort took the cooperation of many
      individuals in a community-based teaching hospital, the largest of six acute care
      hospitals in the state. These efforts have led to a 13% accrual rate to the
      Community Clinical Oncology Program funded by the National Cancer Institute. The
      effort also led to the establishment of multidisciplinary disease site centers
      with representation from the three major physician disciplines of surgery,
      medical oncology, and radiation oncology. In addition, translational research
      projects, a tissue procurement center, and genetic counseling and testing with
      the establishment of a high-risk family cancer registry and collaborative efforts
      with hospitals across the state were established. The current article reviewed
      the continued success of this program in the state of Delaware in the effort to
      reduce the cancer incidence and mortality.

PMID- 15241818
TI  - Novel therapies for myelodysplastic syndromes.
AB  - BACKGROUND: The assessment of patients with myelodysplastic syndromes (MDS) and
      the choice of therapies remain challenging. New therapies are now emerging after
      the identification of molecular targets that result in improvement of hematologic
      parameters and may hold promise for the prevention of disease progression.
      METHODS: A review of the English literature was performed that included original
      articles and related reviews from MEDLINE (PubMed) and abstracts based on
      published meeting material. RESULTS: MDS is a heterogeneous group of disorders.
      Although current classification and prognostic schemes have proven valid to
      define subgroups, they are insufficient to take into consideration the
      significant biologic diversity of MDS. New molecular targets are identified as
      the mosaic of pathophysiologic pathways in MDS is being unraveled. Novel and
      targeted therapeutic agents, such as the inhibition of farnesyl transferases and
      receptor tyrosine kinases, more potent thalidomide analogs, and arsenic trioxide,
      have shown encouraging results and may offer durable benefit to patients with
      MDS. CONCLUSIONS: Although progress has been made in the understanding of
      clinical manifestations and some of the molecular pathways underlying ineffective
      hematopoiesis and leukemic transformation in MDS, intensive clinical and
      laboratory research continues to 1) identify further relevant pathophysiologic
      pathways, 2) better define MDS subgroups, and 3) develop new drugs based on a
      clearer understanding of disease biology.

PMID- 15241819
TI  - Lobular neoplasia on core-needle biopsy--clinical significance.
AB  - BACKGROUND: Approximately 25% of all cases of atypical ductal hyperplasia (ADH)
      diagnosed on core biopsy of the breast are associated with ductal carcinoma in
      situ (DCIS) or invasive malignancy at the same site. As a result, surgical
      excision has become the standard of care for patients with ADH. In contrast,
      because data on the relation between breast malignancy and lobular neoplasia (LN)
      detected on core biopsy are limited, clinical management of patients with LN
      remains controversial. The goal of the current study was to determine the
      incidence of breast carcinoma at sites of core biopsy exhibiting LN compared with
      sites of core biopsy exhibiting ADH. METHODS: The results of 2053 core biopsies
      were reviewed to identify cases of LN and cases of ADH. Follow-up findings on
      excisional biopsy were categorized as malignancy (DCIS or invasive malignancy) or
      no malignancy and were compared between the LN group and the ADH group.
      Mammograms and medical records were reviewed for patients with atypical findings
      on core biopsy. RESULTS: One hundred six (5.2%) of 2053 biopsy samples exhibited
      atypia on core biopsy. Among these 106 samples, ADH was found in 49 (46%), LN was
      found in 45 (42%), and both ADH and LN were found in 12 (12%). Malignant disease
      was detected on follow-up excisional biopsy in 22% of patients with ADH (9 of
      41), 14% of patients with LN (3 of 21), and 33% of patients with both ADH and LN
      (4 of 12) on core biopsy. In the LN group, two cases of malignant disease were
      associated with lobular carcinoma in situ, and the third case was associated with
      atypical lobular hyperplasia. Mammographic and clinical features were unable to
      distinguish patients with malignant findings on excisional biopsy from patients
      without malignant findings. CONCLUSIONS: Malignant disease was found in a
      substantial percentage of excisional biopsy samples (14%) following the detection
      of LN on core biopsy. Thus, like patients with ADH, patients with LN on core
      biopsy could be considered candidates for surgical excision, which would allow
      full assessment of breast carcinoma risk and thereby facilitate the planning of
      prevention strategies.

PMID- 15241820
TI  - Genetic polymorphisms in the human growth hormone-1 gene (GH1) and the risk of
      breast carcinoma.
AB  - BACKGROUND: In addition to possessing many physiologic functions, human growth
      hormone-1 (GH1) has been shown in recent in vitro and in vivo experiments to
      induce malignant disease, including breast carcinoma. The authors investigated
      the association of breast carcinoma with genetic polymorphisms in the GH1 gene in
      the Shanghai Breast Cancer Study. METHODS: Included in the current investigation
      were 1193 women with breast carcinoma (case patients) and 1310 healthy women from
      the same community (control patients) who completed in-person interviews and
      provided blood samples. Genetic polymorphisms in the proximal promoter region
      (nucleotide [nt] -162 to nt +148 relative to the transcription start site of the
      GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study
      participants. A novel polymorphism, a transition from adenine to guanine at nt 69
      (A69G), was identified. Samples from all participants were genotyped with TaqMan
      5' nuclease assays for five common single-nucleotide polymorphisms (SNPs)-four in
      the proximal region (A-75G, G-57T, A-6G, and A69G) and one in intron 4 (T1169A).
      RESULTS: The frequencies of occurrence for the minor alleles in these polymorphic
      sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group;
      these frequencies were comparable to those observed in the case group. After
      adjusting for potential confounding factors, none of the SNPs investigated in
      this study showed a statistically significant association with breast carcinoma
      risk. This null association was found for both younger women (age < 45 years) and
      older women (age > or = 45 years). GH1 gene haplotypes were assessed using SNP
      data and were analyzed in relation to breast carcinoma risk. Again, none of the
      haplotypes were associated with breast carcinoma risk. CONCLUSIONS: The results
      of the current study suggest that genetic polymorphisms in the proximal promoter
      region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma
      risk in Chinese women.

PMID- 15241821
TI  - Lack of association between amplification of her-2 and response to preoperative
      taxanes in patients with breast carcinoma.
AB  - BACKGROUND: The objective of the current study was to determine whether her-2
      amplification was associated with a pathologic response to preoperative
      chemotherapy with taxanes in patients with early-stage breast carcinoma. METHODS:
      The authors evaluated 71 patients treated for AJCC Stage II and III breast
      carcinoma with preoperative taxanes whose tissue specimens were still available.
      Fifty-seven patients (80%) had received paclitaxel and 14 (20%) had received
      docetaxel (4 cycles of either drug). Amplification of the her-2 gene was
      determined using fluorescence in situ hybridization. RESULTS: The median patient
      age was 49 years (range, 21-70 years). Forty-eight patients (68%) had Stage II
      breast carcinoma and 23 (32%) had Stage III disease. her-2 gene amplification was
      detected in 19 tumor specimens (28%). Hormone receptors (estrogen and/or
      progesterone) were detected in 11 her-2-positive tumor specimens (58%) and in 31
      her-2-negative tumor specimens (85%). Eight pathologic complete responses (pCR;
      breast and axillary lymph nodes) occurred, 3 (16%) in patients with her-2
      positive tumor specimens and five (10%) in patients with her-2-negative tumor
      specimens (P = 0.68). Twelve patients achieved pCR in the breast, 5 (26%) in
      patients with her-2-positive tumors and 7 (15%) in patients with her-2-negative
      tumors (P = 0.3). At a median follow-up of 61 months, none of the patients with a
      pCR developed recurrent disease, regardless of their her-2 status. The
      progression-free and overall survival rates were similar in both HER-2-positive
      and her-2-negative groups (P = 0.45 and P = 0.14, respectively). CONCLUSIONS: her
      2 gene amplification was not found to be predictive of a pathologic response to
      preoperative taxanes in patients with early-stage breast carcinoma.

PMID- 15241822
TI  - Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma
      risk and fibroadenoma risk in Caucasian women.
AB  - BACKGROUND: Genes encoding enzymes involved in estrogen metabolism are held to be
      candidate genes for associations with breast disease. In these candidate genes,
      no critical combination of single-nucleotide polymorphisms (SNPs) for assessing
      breast carcinoma risk has been reported to date. METHODS: In a large case-control
      study, the authors investigated 10 estrogen-metabolizing SNPs in 396 patients
      with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control
      patients without breast carcinoma in their personal history. The following 10
      SNPs were analyzed using sequencing-on-chip technology via a solid-phase
      polymerase chain reaction assay performed on oligonucleotide microarrays:
      catechol-O-methyltransferase Val158Met G-->A, 17-beta-hydroxysteroid
      dehydrogenase type 1 vIV A-->C, cytochrome P-450 (CYP) family 17 A2 allele T-->C,
      CYP1A1-1 MspI restriction fragment length polymorphism (RFLP) T-->C, CYP1A1-2
      Ile462Val A-->G, CYP19-1 Trp39Arg T-->C, CYP19-2 Arg264Cys C-->T, CYP19-3
      Cys1558Thr C-->T, steroid-5-alpha reductase type 2 Val89Leu G-->C, and vitamin D
      receptor BsmI RFLP. A total of 21,350 genotypes were evaluated. Associations and
      two-way interaction models were calculated using stepwise logistic regression.
      RESULTS: In a multiple model, CYP1A1-1 (P = 0.004) and CYP1A1-2 (P = 0.03) were
      found to be associated with significantly decreased and increased risks of breast
      carcinoma, respectively. When two-way interactions involving investigated SNPs
      were ascertained, no significant interactions among polymorphisms were noted.
      Comparison of patients with fibroadenoma with control patients revealed
      significantly increased and decreased risks of fibroadenoma when the mutant
      alleles of CYP17 (P = 0.02) and CYP1A1-1 (P = 0.04), respectively, were present.
      CONCLUSIONS: The authors obtained the first SNP data indicating that CYP17 and
      CYP1A1-1 play a role in the pathogenesis of fibroadenoma. Although the authors
      were not able to develop interaction models involving SNPs, they did provide
      evidence that CYP1A1 is a low-penetrance susceptibility gene with respect to
      breast carcinoma in a large series of Caucasian women.

PMID- 15241823
TI  - Human papillomavirus, smoking, and sexual practices in the etiology of anal
      cancer.
AB  - BACKGROUND: The incidence of anal cancer has increased among both men (160%) and
      women (78%) from 1973 to 2000 in the U.S. The authors conducted a population
      based case-control study of anal cancer to examine factors that may account for
      this increase. METHODS: Men (n = 119 patients) and women (n = 187 patients) who
      were diagnosed with anal cancer between 1986 and 1998 in the Seattle area were
      ascertained through the local Surveillance, Epidemiology, and End Results
      registry. Control participants (n = 1700) were ascertained through random-digit
      telephone dialing. Participants were interviewed in person and provided blood
      samples. Archival tumor tissue was tested for human papilloma virus (HPV) DNA,
      and serum samples were tested for HPV type 16 (HPV-16). RESULTS: Overall, 88% of
      tumors (all histologies) in the study were found to be positive for HPV. HPV-16
      was the most frequent HPV type detected (73% of all tumors), followed by HPV-18
      (6.9%), regardless of gender. However, 97.7% of tumors from men who were not
      exclusively heterosexual contained HPV DNA. The risk of anal cancer increased
      among men (odds ratio [OR], 5.3; 95% confidence interval [95% CI], 2.4-12.0) and
      women (OR, 11.0; 95% CI, 5.5-22.1) who had > or = 15 sexual partners during their
      lifetime. Among men who were not exclusively heterosexual and women, receptive
      anal intercourse was related strongly to the risk of anal cancer (OR, 6.8 [95%
      CI, 1.4-33.8] and OR, 2.2 [95% CI, 1.4-3.3], respectively). Current smokers among
      men and women were at particularly high risk for anal cancer, independent of age
      and other risk factors (OR, 3.9 [95% CI, 1.9-8.0] and OR, 3.8 [95% CI, 2.4-6.2],
      respectively). CONCLUSIONS: The high proportion of tumors with detectable HPV
      suggests that infection with HPV is a necessary cause of anal cancer, similar to
      that of cervical cancer. Increases in the prevalence of exposures, such as
      cigarette smoking, anal intercourse, HPV infection, and the number of lifetime
      sexual partners, may account for the increasing incidence of anal cancer in men
      and women.

PMID- 15241824
TI  - Anal cancer incidence and survival: the surveillance, epidemiology, and end
      results experience, 1973-2000.
AB  - BACKGROUND: Anal cancer is a rare malignancy of the anogenital tract that
      historically has affected women at a greater rate than men. METHODS: The authors
      analyzed changing trends in incidence rates and 5-year relative survival
      percentages for patients with anal cancer. The publicly available data used in
      the current study were obtained from the Surveillance, Epidemiology, and End
      Results (SEER) Program, a system of population-based tumor registries in the
      United States. RESULTS: The incidence of anal cancer was similar for men and
      women between 1994 and 2000 (2.04 per 100,000 and 2.06 per 100,000,
      respectively), the most recent period for which data were available, whereas men
      had lower rates than did women between 1973 and 1979 (1.06 per 100,000, compared
      with 1.39 per 100,000), the earliest period for which data were available. In
      addition, recently, black men had higher incidence rates than did other race
      specific and gender-specific groups (2.71 per 100,000). From the earliest period
      for which data were available to the most recent period, relative 5-year survival
      improved from 59% to 73% among women, was unchanged among men ( approximately
      60%), and decreased from 45% to 27% among black men. Eighteen percent of patients
      who had distant disease were alive at 5 years, compared with 78% of patients who
      had localized disease. CONCLUSIONS: The incidence of anal cancer in the United
      States increased between 1973 and 2000, particularly among men. There were higher
      incidence rates and lower survival rates for black men compared with other race
      specific and gender-specific groups. Later disease stage was inversely associated
      with the survival rate, indicating that earlier detection may improve the
      survival of patients with anal cancer.

PMID- 15241825
TI  - Adult Wilms' tumor: A monoinstitutional experience and a review of the
      literature.
AB  - BACKGROUND: The authors reviewed their institutional experience regarding adult
      patients with Wilms' tumor (WT) to assess their clinical characteristics and
      compliance with respect to children's treatment guidelines. METHODS: A total of
      17 adult patients (median age at the time of diagnosis of 17.5 years; range, 16
      29 years) were referred to the study institute between 1983 and 2001 and were
      followed for a median of 131 months. The treatment modality was planned according
      to the two consecutive Italian protocols for WT that were active during the
      referral years. The patients were staged according to the National Wilms Tumor
      Study-4 (NWTS) staging system as follows: eight patients had Stage II disease,
      four patients had Stage III disease, and five patients had Stage IV disease.
      RESULTS: All the patients but one underwent nephrectomy, with three incomplete
      surgeries performed. Two patients with Stage II disease were treated elsewhere
      with nephrectomy only and they were admitted to the study institution at the time
      of disease recurrence. Anaplasia was found to be present in only one patient with
      Stage IV disease. The authors noted 9 cases of disease recurrence or progression
      occurring during treatment and 6 of these 9 patients died of their disease, with
      an overall survival rate of 62.4% at 5 years. CONCLUSIONS: Compared with
      children, adults with WT are reported to have a worse prognosis. In the current
      study, the authors found that poor compliance with specific therapeutic
      guidelines may contribute to this poorer outcome. Because of the rarity of this
      disease, adults with WT are at a risk of either undertreatment or incorrect
      treatment.

PMID- 15241826
TI  - Prostate carcinoma among men with human immunodeficiency virus infection.
AB  - BACKGROUND: Several malignancies are known to occur more frequently in
      individuals with human immunodeficiency virus (HIV) infection. To determine the
      incidence of prostate carcinoma in men with HIV infection, the authors initiated
      a prostate carcinoma screening program in a large HIV clinic. METHODS: Beginning
      in February 2002, monitoring of prostate-specific antigen (PSA) levels and
      digital rectal examination (DRE) were included in the routine annual health
      maintenance provided to men with HIV infection age > or = 35 years who were
      followed in the infectious disease clinic at the Naval Medical Center San Diego.
      All men with prostate carcinoma in this population over the last 2 years were
      reviewed. Demographic data (age, ethnicity), duration of HIV infection,
      laboratory values (CD4 counts and HIV viral load), and medication use were
      determined by medical record review. Men with elevated PSA levels (levels above
      age-adjusted PSA values or PSA velocity > or = 0.75 ng/mL per year) or abnormal
      DRE results were referred for urologic evaluation. Comparisons between groups
      were performed using a logistic regression model and the Fisher exact test.
      Multivariate analysis was performed by logistic regression to determine relations
      between prostate carcinoma and patient characteristics. RESULTS: Two hundred
      sixty-nine men age > or = 35 years (mean age, 43.4 years; range, 35-72years)
      underwent prostate carcinoma screening by DRE, and 216 men also received PSA
      testing. Overall, 56.3% of the patients were white, 28.7% were African American,
      and 15% were of other racial ethnicity. Of the 216 men, 7 (3.2%) had elevated PSA
      values, and none had abnormal DRE results. Three patients were diagnosed with
      prostatitis (PSA range, 3.3-25.7 ng/mL), and 1 patient had high-grade prostatic
      intraepithelial neoplasia, which was determined after a biopsy was performed.
      Repeat PSA evaluations were within normal limits for the remaining three
      patients. Review of the cohort during the 2-year period before the current study
      was initiated revealed 5 additional cases of prostate neoplasia. Prostate
      carcinoma was common (4 of 11 men, 36.4%) in men age > 60 years and occurred with
      relatively preserved CD4 counts (mean, 509 cells/mm(3)). In multivariate
      analysis, African-American race (P = 0.020) and duration of HIV infection (P =
      0.047) were found to be associated with the development of prostate carcinoma.
      CONCLUSIONS: Prostate carcinoma screening identified abnormal PSA values in 3.2%
      of the HIV-positive cohort, many associated with prostatitis. Prostate carcinoma
      was common in older men and was associated with duration of HIV infection. As the
      life expectancy of men with HIV infection increases, prostate carcinoma screening
      will become increasingly important in this population.

PMID- 15241827
TI  - Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable
      prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group.
AB  - BACKGROUND: The current study was conducted to examine the pattern and the
      predictive factors of distant metastases (DM) in patients with nasopharyngeal
      carcinoma (NPC) after primary radiotherapy treatment. METHODS: Data from all five
      regional cancer centers in Hong Kong were collected retrospectively and pooled
      for the current study, which was coordinated by the Hong Kong Nasopharyngeal
      Carcinoma Study Group. The sample was comprised of all 2915 patients with NPC
      without DM at the time of presentation who were treated with radiotherapy in 1 of
      the 5 cancer centers during the period between January 1996 and December 2000.
      RESULTS: DM was found to be the leading cause of NPC failure, with a 5-year
      actuarial rate of 14.9% in this patient cohort. Despite the poor overall survival
      (OS) of these patients, those with lung metastasis alone represented a
      distinctive group associated with a significantly better OS. International Union
      Against Cancer (UICC) N classification, UICC T classification, advanced age, and
      male gender were found to be significant and independent determinants for DM.
      CONCLUSIONS: Long-term survival is possible in patients with distant metastatic
      NPC confined to the lung. An aggressive approach to treatment for this group of
      patients should be considered.

PMID- 15241828
TI  - Prognostic impact of hemoglobin levels on treatment outcome in patients with
      nasopharyngeal carcinoma treated with sequential chemoradiotherapy or
      radiotherapy alone.
AB  - BACKGROUND: The goal of the current study was to investigate the impact of
      hemoglobin (Hb) levels on treatment outcome in a randomized Phase III trial of
      patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy
      followed by radiotherapy or with radiotherapy alone. METHODS: Between September
      1989 and August 1993, 334 patients with advanced NPC were entered into a
      randomized trial comparing 3 cycles of induction chemotherapy (cisplatin and
      epirubicin) followed by radiotherapy with radiotherapy alone. Only evaluable
      patients who completed radiation were included in the analysis (n = 286).
      Patients were stratified into normal and low Hb groups according to baseline,
      preradiation, and midradiation Hb levels. Local recurrence-free, distant
      metastasis-free, and disease-specific survival rates were estimated using the
      Kaplan-Meier method. Multivariate analysis was performed using the Cox model.
      RESULTS: In the chemotherapy arm, the mean baseline, preradiation, and
      midradiation Hb levels were 13.6, 11.0, and 11.8 g/dL, respectively. In the
      radiotherapy arm, the mean baseline/preradiation and midradiation Hb levels were
      13.7 and 12.9 g/dL, respectively. A midradiation Hb level < or = 11 g/dL was
      associated with significantly poorer 5-year local recurrence-free (60% vs. 80%; P
      = 0.0059) and disease-specific survival rates (51% vs. 68%; P = 0.001), with no
      difference in distant metastasis-free rates (69% vs. 67%; P = 0.83). No
      significant difference in treatment outcome according to baseline or preradiation
      Hb levels was noted. Multivariate analysis showed that a low midradiation Hb
      level, but not a low baseline or preradiation Hb level, was an independent
      predictor of local disease recurrence and malignancy-related death. CONCLUSIONS:
      The current study showed that midradiation Hb level was an important prognostic
      factor with respect to local control and survival in patients with NPC. The high
      incidence of anemia after chemotherapy has a negative impact on treatment
      outcome, and this condition may reduce the benefit of induction chemotherapy.
      Attempts to correct anemia during radiation and the impact of anemia on treatment
      outcome requires further study.

PMID- 15241829
TI  - Malignancy-related causes of death in human immunodeficiency virus-infected
      patients in the era of highly active antiretroviral therapy.
AB  - BACKGROUND: Before the introduction of highly active antiretroviral therapy
      (HAART), malignancies accounted for less than 10% of all deaths among human
      immunodeficiency virus (HIV)-infected patients. This figure may have increased,
      and the observed types of malignant disease may have been modified, as a result
      of decreased occurrence of opportunistic infections, the chronicity of HIV
      infection, the possible oncogenic role of HIV itself, and the aging of the HIV
      infected population. METHODS: All French hospital wards involved in the
      management of HIV infection were asked to prospectively document the deaths of
      HIV-infected patients in the year 2000. Underlying causes of death were defined
      using a standardized questionnaire. RESULTS: Of a total of 964 deaths, 269 (28%)
      were attributable to malignancies. Acquired immunodeficiency virus (AIDS)-related
      malignancies were the underlying cause of 149 deaths (15%); among these
      malignancies were non-Hodgkin lymphoma (n = 105 [11%]), noncerebral lymphoma (n =
      78 [median CD4 count, 86 x 10(6) per liter; interquartile range [IQR], 35-231 x
      10(6) per liter), and primary cerebral lymphoma (n = 27 [median CD4 count, 20 x
      10(6) per liter; IQR, 4-109 x 10(6) per liter). Kaposi sarcoma was associated
      with 40 deaths (4%), and cervical carcinoma was associated with 5 (0.5%). Non
      AIDS-related malignancies were the underlying cause of 120 deaths (13%); these
      non-AIDS-related malignancies included 103 solid tumors (50 respiratory tumors,
      19 hepatocarcinomas, 9 digestive tumors, and 6 anal tumors; median CD4 count, 218
      x 10(6) per liter; IQR, 108-380 x 10(6) per liter) and 17 hemopathies (12 Hodgkin
      lymphomas, 4 myeloid leukemias, and 1 myeloma; median CD4 count, 113 x 10(6) per
      liter; IQR, 56-286 x 10(6) per liter). Compared with patients who died of other
      causes, patients who died of solid tumors were more likely to be male, to smoke,
      to be older, and to have higher CD4 counts. CONCLUSIONS: Malignant disease has
      been a major cause of death among HIV-infected patients in industrialized nations
      since the introduction of HAART. Whereas lethal hemopathies and Kaposi sarcoma
      are associated with advanced immunosuppression, lethal solid tumors can occur in
      patients with controlled HIV infection.

PMID- 15241830
TI  - The benefit of induction chemotherapy in patients age > or = 75 years.
AB  - BACKGROUND: Patients age > or = 75 years with acute myeloid leukemia (AML)
      generally are offered palliative treatments instead of induction chemotherapy.
      The authors conducted a retrospective study comparing the outcomes among these
      elderly patients with the outcomes among younger patients to assess the impact of
      intensive treatment approaches in this age group. METHODS: One hundred ten
      consecutive patients age > or = 75 years with newly diagnosed AML (excluding
      patients with acute promyelocytic leukemia) were treated in the authors' center
      over 10 years. Initial treatment was comprised of anthracycline-based induction
      chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus
      cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients
      (56%), antimetabolite-based chemotherapy (including low-dose ARAC, oral 6
      mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and
      supportive care only for 8 patients (7%). Results were compared with the results
      from 200 patients ages 65-74 years who were treated during the same period.
      RESULTS: A complete response (CR) to anthracycline-based induction therapy was
      achieved by 23 of 62 patients (37%), and the 2-year overall survival rate was 22%
      (which was not statistically different from the group of patients ages 65-74
      years). In a multivariate analysis of the entire study group (310 patients),
      treatment (anthracycline-based vs. other) and age as continuous variable were
      found to affect survival significantly. In a Landmark analysis, the achievement
      of a CR translated into improved survival in patients age > or = 75 years.
      CONCLUSIONS: Patients age > or = 75 years should not be excluded systematically
      from intensive chemotherapy regimens. Decisions should be based on stratification
      systems that include functional status and comorbidity assessments as well as
      prognostic factors, such as cytogenetics.

PMID- 15241831
TI  - Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic
      myelogenous leukemia.
AB  - BACKGROUND: Reticulin-stained bone marrow fibrosis is associated with a poor
      prognosis in patients with chronic myelogenous leukemia (CML). Resolution of
      fibrosis with therapy may improve patient outcome. METHODS: The effect of
      imatinib therapy on bone marrow fibrosis was evaluated in 40 patients with
      chronic-phase CML who were treated after interferon-alpha failure. RESULTS:
      Thirty-one patients (78%) had severe (Grade 3 or 4) reticulin fibrosis prior to
      therapy. After imatinib therapy was administered for 3 to > 24 months, fibrosis
      was reduced by at least 2 grades in 19 of the 31 patients (61%) and by at least 1
      grade in 34 patients (85%). There was no correlation noted between reduction of
      fibrosis and cytogenetic response. However, a reduction in fibrosis was found to
      correlate with a reduction in bone marrow megakaryocytosis (P = 0.002).
      CONCLUSIONS: Treatment with imatinib mesylate appears to reduce CML-associated
      bone marrow fibrosis in most patients who are treated during the chronic phase of
      disease. This effect may be independent of the degree of suppression of
      Philadelphia chromosome-positive cells, and may improve prognosis in patients
      with CML.

PMID- 15241832
TI  - Transjugular intrahepatic portosystemic shunts: experience in the oncology
      setting.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement has
      emerged as an effective and minimally invasive method of treating portal
      hypertension and its associated complications. To the authors' knowledge there is
      limited documentation of its use for percutaneous shunting in patients with
      hepatic and extrahepatic malignancies. The current study reports the authors'
      experience with TIPS in the oncology setting. METHODS: Thirty-eight patients with
      cancer underwent TIPS procedures. Nineteen patients had a history of hepatic
      malignancy. All medical records and imaging studies were reviewed
      retrospectively. The indication for TIPS, the presence of malignancy, procedural
      details, complications, survival, and treatment success were assessed. RESULTS:
      Primary technical success was accomplished in 37 of 38 patients (97%) without
      technical procedure-related complications. Hepatic encephalopathy occurred in 15
      of 34 patients (44%), with 3 patients requiring shunt reduction. Premature shunt
      occlusion (< 30 days) occurred in 3 patients (8%). Recurrent hemorrhage occurred
      in 1 of 19 patients (5%), and ascites and hepatic hydrothorax resolved or
      improved subjectively in 9 of 12 patients (75%). Shunts traversed malignancy in 9
      patients, and varying degrees of portal compromise were encountered in 12
      patients (32%). The overall 30-day and 90-day survival rates were 84% and 60%,
      respectively. There was a statistically significant difference in 90-day survival
      rates for patients who had ascites and hepatic hydrothorax indications (27%)
      compared with patients who had variceal and portal gastropathy indications (84%;
      P = 0.0075). In addition, the 90-day survival rate was significantly lower in
      patients who had primary hepatic malignancies (36%) compared with the remainder
      of the study population (74%; P = 0.0077), and it was significantly lower in
      patients who had model for end-stage liver disease (MELD) scores > or = 12 (P =
      0.0020). CONCLUSIONS: TIPS was performed safely for patients with cancer without
      increasing rates of procedure-related complications. However, some patients
      subgroups, such at those with malignancy and ascites, primary hepatic malignancy,
      or MELD scores > or = 12, had the lowest 90-day survival rates.

PMID- 15241833
TI  - The utility of computed tomography scans in predicting suboptimal cytoreductive
      surgery in women with advanced ovarian carcinoma.
AB  - BACKGROUND: Computed tomography (CT) scans of the abdomen and pelvis may predict
      which patients with ovarian carcinoma can undergo optimal cytoreduction at
      primary surgery. Previous studies have demonstrated that patients with ovarian
      carcinoma had optimal cytoreduction rates ranging from 50-60%. The authors sought
      to determine whether these findings applied to a surgical practice with a higher
      rate of optimal debulking. A predictive model using CT scanning and CA 125 values
      would allow the authors to determine which patients would be more appropriately
      treated with neoadjuvant chemotherapy. METHODS: Preoperative CT scans for
      patients with Stage III/IV ovarian carcinoma (according to the staging system of
      the International Federation of Gynecology and Obstetrics) who were treated
      between 1996 and 2001 were evaluated retrospectively by 2 radiologists for 17
      criteria evaluating the extent of disease. Clinical data were extracted from
      medical records. Residual tumors measuring > or = 1 cm were considered
      suboptimal. Logistic regression was used to evaluate which criteria correlated
      with optimal cytoreduction. RESULTS: Eighty-seven patients were identified
      retrospectively who met entry criteria and had preoperative CT scans of
      sufficient diagnostic quality. Sixty-two patients (71%) received optimal
      cytoreductive surgery and 45 (52%) required aggressive surgical procedures. In a
      multivariate model, only diffuse peritoneal thickening (DPT) independently
      predicted suboptimal surgical resection (P = 0.016). However, a model using both
      DPT and ascites on most CT scans had a positive predictive value of 68% and a
      sensitivity of 52% for predicting suboptimal cytoreduction. CONCLUSIONS: The
      presence of DPT and large-volume ascites was associated with a very low rate of
      optimal cytoreduction (32%) in a surgical practice. These patients may be more
      appropriately treated with neoadjuvant chemotherapy followed by surgical
      cytoreduction.

PMID- 15241834
TI  - Reproductive factors and risk of breast carcinoma in a study of white and African
      American women.
AB  - BACKGROUND: Few studies have investigated the association between reproductive
      factors and the risk of breast carcinoma among African-American women. The
      authors assessed whether the number of full-term pregnancies, age at first full
      term pregnancy, and total duration of breastfeeding were associated with similar
      relative risk estimates in white and African-American women in a large
      multicenter, population-based case-control study of breast carcinoma. METHODS:
      Case patients were 4567 women (2950 white women and 1617 African-American women)
      ages 35-64 years with newly diagnosed invasive breast carcinoma between 1994 and
      1998. Control patients were 4668 women (3012 white women and 1656 African
      American women) who were identified by random-digit dialing and were frequency
      matched to case patients according to study center, race, and age. Adjusted odds
      ratios and 95% confidence intervals were estimated using unconditional logistic
      regression. RESULTS: For white women, the reduction in risk of breast carcinoma
      per full-term pregnancy was 13% among younger women (ages 35-49 years) and 10%
      among older women (ages 50-64 years). The corresponding risk reductions for
      African-American women were 10% and 6%, respectively. Risk decreased
      significantly with increasing number of full-term pregnancies for both races and
      both age categories. Duration of lactation was inversely associated with breast
      carcinoma risk among younger parous white (trend P = 0.0001) and African-American
      (trend P = 0.01) women. African-American women tended to have more children
      compared with white women, but parity rates were lower in younger women than in
      older women in both racial groups. However, breastfeeding was substantially more
      common in young white women than in young African-American women. CONCLUSIONS:
      Overall, parity and lactation had similar effects on breast carcinoma risk in
      white and African-American women. If younger African-American women now are
      giving birth to fewer children than in the past, without a substantial increase
      in breastfeeding, breast carcinoma rates may continue to increase at a more rapid
      rate among these women compared with white women.

PMID- 15241835
TI  - Familial risk and clustering of nasopharyngeal carcinoma in Guangdong, China.
AB  - BACKGROUND: Previous studies have suggested that genetic susceptibility may play
      an important role in the etiology of nasopharyngeal cancer (NPC). However, to
      date, few large-scale studies have been conducted on familial risk and clustering
      of NPC in a high-risk area of China. METHODS: In the current study, 2252 patients
      with NPC who were treated at the Cancer Center of Sun Yat-Sen University in
      Guangdong Province, China, were identified as probands. Family histories of NPC
      and other malignancies were observed in first-degree relatives (FDRs) and second
      degree relatives, and other information was obtained through interviews. One
      thousand nine hundred and three Cantonese families were selected for further
      investigation. To assess familial aggregation, the authors used standardized
      incidence ratios (SIRs) to measure the risk of NPC for FDRs and compared the
      observed number of cases with the number predicted by population-based
      frequencies in the Cantonese population of Hong Kong. RESULTS: The current
      analysis indicated that families with > or = 3 relatives who had NPC were
      distributed predominantly among a high-risk subgroup of the Cantonese population
      in Guangdong Province and that the frequency of these families was 0.68%. An SIR
      of 2.09 (95% confidence interval [CI], 1.80-2.40) was observed among 13,833 FDRs
      in the high-risk subgroup, and a significantly elevated risk for NPC was observed
      in FDRs of probands with early age of onset (age < 40 years; SIR, 9.01 [95% CI,
      6.10-13.30]). Furthermore, decreased risks of hepatic, lung, esophageal, gastric,
      and breast carcinoma, as well as malignancy of all sites, were observed among
      FDRs of probands with NPC when Hong Kong and Shanghai populations were used as
      reference groups. CONCLUSIONS: NPC tends to aggregate in Cantonese families in
      Guangdong Province, and the malignancies in these families appear to be site
      specific, with no excess of any other malignancy.

PMID- 15241836
TI  - Phase II study of high-dose fish oil capsules for patients with cancer-related
      cachexia.
AB  - BACKGROUND: The authors undertook a multiinstitutional Phase II cooperative group
      study to examine the potential of oral fish oil fatty acid supplements
      administered at high doses to slow weight loss and to improve quality of life in
      patients with malignancy-related cachexia. METHODS: Patients with advanced
      malignancy and weight loss > or = 2% of body weight in the preceding month took
      concentrated, high-dose omega-3 fatty acid capsules (7.5 g eicosapentaenoic acid
      plus docosahexaenoic acid for a 70 kg individual) that were supplied by the
      National Institutes of Health. RESULTS: Forty-three patients with moderate or
      severe malnutrition were enrolled. The median time receiving treatment was 1.2
      months. For the 36 patients who took at least 1 capsule and did not have edema,
      there was a weight change ranging from -6.2 kg to +3.5 kg and an overall median
      weight loss of 0.8 kg. Twenty-four patients had weight stabilization (a gain of <
      or = 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6
      patients lost > or = 5% of their body weight. There was marked variability in the
      tolerability of the capsules, and many patients had gastrointestinal side
      effects. There was a correlation between time receiving treatment and weight gain
      for the 22 patients who were able to tolerate the capsules for at least 1 month.
      Quality-of-life scores were superior for patients who gained weight. CONCLUSIONS:
      A majority of patients did not gain weight, and in that sense, the results of the
      study were unfavorable. However, a small but definite subset of patients had
      weight stabilization or weight gain. This suggests that omega-3 fatty acids have
      potential utility at the study doses, which were more than twice the doses used
      in published Phase III studies.

PMID- 15241837
TI  - Clinical utility of serum amyloid A and macrophage migration inhibitory factor as
      serum biomarkers for the detection of nonsmall cell lung carcinoma.
AB  - BACKGROUND: Early lung carcinoma detection strategies involving imaging studies
      have yet to demonstrate a reduction in mortality. Identification of serum
      biomarkers that could complement radiologic studies and facilitate earlier
      diagnosis of lung carcinoma would be of significant benefit to patients. In the
      current pilot study, the authors evaluated two overexpressed proteins in lung
      carcinoma, serum amyloid A (SAA) and macrophage migration inhibitory factor
      (MIF), as potential diagnostic serum biomarkers for this malignancy. METHODS:
      Serum levels of SAA and MIF were measured in 50 patients using enzyme-linked
      immunosorbent assays. The sensitivity, specificity, and accuracy of the markers
      in detecting lung carcinoma were determined. RESULTS: SAA levels in patients with
      lung carcinoma were greater than in the control patients (P = 0.07). Serum SAA
      levels did not exhibit a correlation with tumor size or clinical stage and were
      higher in patients with squamous cell carcinoma than in patients with other
      histologic disease types. MIF was unable to differentiate patients with lung
      carcinoma from patients with other diseases. CONCLUSIONS: SAA possesses potential
      utility as a serum biomarker for lung carcinoma, probably in conjunction with
      other serum markers that improve its diagnostic accuracy. Before a larger study
      is performed, the discovery of additional biomarkers to enhance the specificity
      of SAA in the diagnosis of lung carcinoma is recommended.

PMID- 15241838
TI  - Long-term results of the first Italian Association of Pediatric Hematology and
      Oncology protocol for the treatment of pediatric B-cell non-Hodgkin lymphoma
      (AIEOP LNH92).
AB  - BACKGROUND: Childhood B-cell lymphomas (B-NHLs) represent a group of aggressive
      malignancies that are amenable to high-intensity chemotherapy regimens. In 1992,
      the Italian Association of Pediatric Hematology and Oncology (AIEOP) initiated a
      prospective clinical trial involving the diagnosis and treatment of childhood B
      NHL based on a well established strategy developed by the Berlin-Frankfurt
      Munster Group. METHODS: Between November 1992 and October 1997, 163 children who
      had B-NHL were treated prospectively in the first national AIEOP trial. Disease
      staging was performed according to the St. Jude staging system, and treatment was
      assigned on the basis of risk group (R1, R2, or R3), which took into account
      disease stage and resectability and serum lactate dehydrogenase (LDH) levels.
      RESULTS: Of the 144 evaluable patients, 11 had Stage I disease, 35 had Stage II
      disease, 76 had Stage III disease, and 22 had Stage IV disease. Thirteen, 54, and
      77 patients were included in risk groups R1, R2, and R3, respectively. The 10
      year overall survival (OS) and event-free survival (EFS) rates for the overall
      population were 89.4% and 81.8%, respectively; the EFS rates for patients in risk
      groups R1, R2, and R3 were 100%, 86.9%, and 75.1%, respectively. Multivariate
      analysis indicated that age > or = 10 years, disease histology other than Burkitt
      or Burkitt-like lymphoma, and LDH levels > or = 1000 international units per
      liter had negative prognostic value. Analysis of the toxicity (according to the
      World Health Organization grading system) associated with 710 of the 748
      chemotherapy cycles administered revealed 855 cases of Grade 3 or 4 toxicity,
      with 73% being cases of hematologic toxicity. Toxic episodes were most common
      after the first chemotherapy cycle and were equally common in the R2 and R3 risk
      groups. To date, the development of a second malignancy has not been observed in
      any patient in the study cohort. CONCLUSIONS: Long-term follow-up of the current
      study (AIEOP LNH92) confirms the observation of a favorable outcome for patients
      with B-NHL treated with short, intensive chemotherapy regimens and raises the
      possibility that non-Burkitt or non-Burkitt-like histology and age > or = 10
      years may have negative prognostic value for patients with childhood B-NHL.

PMID- 15241839
TI  - Psychologic distress after disclosure of genetic test results regarding
      hereditary nonpolyposis colorectal carcinoma.
AB  - BACKGROUND: To the authors' knowledge, there have been few studies of the
      psychologic distress after disclosure of genetic test results for hereditary
      nonpolyposis colorectal carcinoma (HNPCC). The objectives of this study were to
      identify the prevalence rates and predictors of psychologic distress and to
      evaluate the feelings of guilt after disclosure of the test results in Japanese
      probands and unaffected relatives. METHODS: Probands and unaffected relatives
      were interviewed immediately after the first genetic counseling session for HNPCC
      and again 1 month after disclosure of the genetic test results. The prevalence of
      major and minor depression, acute stress disorder (ASD), posttraumatic stress
      disorder (PTSD), and posttraumatic stress symptoms (PTSS) were assessed using the
      Structured Clinical Interview based on the Diagnostic and Statistical Manual of
      Mental Disorders, 3rd edition revised (DSM-III-R) or the DSM-IV; feelings of
      guilt were investigated using a numeric scale and a semistructured interview.
      RESULTS: Among 47 participants who completed the baseline interview, 42
      participants (89%) completed the 1-month follow-up interview. Although none of
      the participants met the criteria for major depression, ASD, or PTSD at the
      follow-up interview, 3 of 42 participants (7%) met the criteria for minor
      depression and 2 participants (5%) had PTSS. The only predictor of psychologic
      distress found was the presence of a history of major or minor depression (odds
      ratio, 19.41; 95% confidence interval, 1.42-264.95; P < 0.05). Five of 42
      participants (12%) had feelings of guilt. CONCLUSIONS: Disclosure of genetic test
      results for HNPCC may not cause significant psychologic distress in Japanese
      probands or relatives. However, healthcare providers should not neglect to assess
      these individuals for psychologic responses, such as minor depression and PTSS.

PMID- 15241840
TI  - Prospective assessment of emotional distress, cognitive function, and quality of
      life in patients with cancer treated with chemotherapy.
AB  - BACKGROUND: The current study sought to delineate prospectively the rates and
      clinical course of emotional distress, cognitive impairment, and quality of life
      (QOL) in chemotherapy-naive patients with cancer and to consider the determinants
      of global QOL. METHODS: Patients who consented to participate were administered
      the European Organization for Research and Treatment of Cancer QLQ-C30
      questionnaire, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety
      and Depression Scale before and at the end of treatment (EOT). RESULTS: Of the
      102 patients initially assessed, 80 (78.4%) completed the study. Most aspects of
      QOL did not change considerably over time. At EOT, patients reported only
      significant increases in fatigue and significant decreases in sleep disturbance.
      Although no significant changes emerged in the rates of anxiety or depression
      throughout chemotherapy, nearly one-third of the patients experienced severe
      emotional distress at both points in time. In addition, the authors observed
      neither significant alteration in the cognitive performance over time nor
      reliable associations between scores on the MMSE and subjective cognitive
      function, emotional distress, or QOL. Finally, depression proved to be the
      leading predictor of global QOL at baseline and at EOT. CONCLUSIONS: The results
      indicated that a significant proportion of Greek patients with cancer experienced
      intense anxiety and depression throughout chemotherapy and confirmed the
      importance of depression as a strong predictor of global QOL. Routine screening
      of emotional distress across all phases of cancer is mandatory because it will
      contribute to the identification of patients who are in need of pharmaceutical
      and/or psychologic intervention.

PMID- 15241841
TI  - Intensity-modulated radiotherapy and the Internet.
AB  - BACKGROUND: The objective of the current study was to evaluate the content and
      quality of patient-oriented information regarding intensity-modulated
      radiotherapy (IMRT) on the Internet. METHODS: IMRT websites were identified by
      reviewing the first 50 uniform resource locators on 5 search engines using the
      search terms IMRT and intensity modulated radiation therapy. Each site was
      evaluated by three observers for informational content, presentation, accuracy,
      and balance. A score of low, moderate, or high was assigned to each category
      based on a predefined scoring system. An overall score was assigned to each site,
      ranging from -35 to 100 points. RESULTS: Seventy-seven patient-oriented IMRT
      websites were identified (45% private, 21% academic, and 18% commercial). Most
      sites (58%) had a low level of informational content, with information on
      fundamental aspects of IMRT planning (target delineation and inverse planning)
      appearing on < 50% of sites. The most commonly discussed tumors were
      genitourinary (65%) and head and neck (53%) lesions. Few sites, however,
      described the potential benefits of IMRT (toxicity and tumor control). Most sites
      (82%) used patient-appropriate language. False and/or misleading information was
      seen on 42% of sites and was equally common on academic, private, and commercial
      sites. Balance statements were present on 24% of sites (most of which were
      commercial). The median overall score was 20 points (range, -25 to 70 points).
      The median overall scores for academic, private, commercial, and other sites were
      10, 20, 25, and 20 points, respectively (P = 0.26). CONCLUSIONS: In general, the
      content and quality of patient-oriented information regarding IMRT on the
      Internet were poor. Patients and their physicians need to be aware of these
      problems when selecting treatment courses.

PMID- 15241842
TI  - Predictors of place of death for Japanese patients with advanced-stage malignant
      disease in home care settings: a nationwide survey.
AB  - BACKGROUND: Although the place of death for patients with advanced malignancy is
      influenced by multiple factors, few studies have systematically investigated the
      determinants of place of death. The objective of the current retrospective study
      was to clarify the predictors of home death throughout the duration of home
      palliative care for Japanese patients with advanced malignant disease. METHODS:
      In the current nationwide survey, the authors investigated predictors involving
      patient demographics and clinical profiles, the roles and status of family
      caregivers, and the support provided by the healthcare system in the introductory
      phase (during the first week of home care), the stable phase (between the
      introductory and dying phases), and the dying phase (during the final week before
      death) of home care service in Japan. RESULTS: Multivariate logistic regression
      models clarified that 1) patient-related clinical variables (e.g., functional
      status and rehospitalization); 2) the support of the healthcare system (e.g.,
      provision of information on the dying process and visitation by home care
      nurses); and 3) the status and roles of family caregivers (e.g., psychologic
      distress levels, assistance with patient evacuation, etc.) have an effect on
      place of death throughout all three phases of home palliative care. Overall, the
      model used in the current study was able to predict 94% of home deaths
      accurately. CONCLUSIONS: A clearer understanding of factors that may influence
      place of death for patients with advanced-stage malignant disease would allow
      healthcare professionals to modify healthcare systems and tailor effective
      interventions to help patients die in their preferred location.

PMID- 15241843
TI  - Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicenter study.

PMID- 15241844
TI  - Elevated perioperative serum vascular endothelial growth factor levels in
      patients with colon carcinoma.

PMID- 15241849
TI  - When CD4-cell count is nearly as undetectable as the viral load.

PMID- 15241847
TI  - Groundwater arsenic contamination and its health effects in the Ganga-Meghna
      Brahmaputra plain.

PMID- 15241848
TI  - Study design questions in treatment of children with acute otitis media.

PMID- 15241850
TI  - National HIV/AIDS forces unite for HIV testing day.

PMID- 15241852
TI  - Bias. Family of HIV-positive stroke victim sues nursing homes.

PMID- 15241853
TI  - FTC halts U.S. sales of defective HIV home test kits.

PMID- 15241851
TI  - Report summarizes American perceptions of AIDS epidemic.

PMID- 15241854
TI  - FTC: home-use tests for HIV can be inaccurate.

PMID- 15241855
TI  - HIV funding. Report predicts tax cut effects on HIV, other programs.

PMID- 15241856
TI  - New Medicare-approved prescription drug discount card.
AB  - Patients who are on Medicare and have income under 135% of Federal poverty level
      and are not on Medicaid probably should obtain one of the new Medicare discount
      cards that became available on June 1, 2004, because all these cards include $600
      annual credit for prescription-drug purchases for persons within that income
      limit. Unfortunately this program is complex, no one yet knows how it will work
      in practice, and after choosing a card one is locked in and cannot change cards
      until November 15. The most difficult part of the choice of which card to get may
      involve how it interacts with other programs, including ADAP, and pharmaceutical
      company patient assistance programs.

PMID- 15241857
TI  - Institute of Medicine urges restructuring of U.S. low-income HIV treatment and
      care.
AB  - The U.S. could prevent thousands of unnecessary deaths by creating a
      comprehensive HIV care program. It would be administered by the states under
      Federal standards of patient care and physician reimbursement, and replace
      Medicaid (for persons with HIV), ADAP, and much of Ryan White as well.

PMID- 15241858
TI  - New York City group leads the way toward a more optimistic future for ASOs. ASO
      went from near bankruptcy to $26 million.
AB  - A do-it-yourself AIDS social organization: AIDS service organizations are
      struggling because of tighter reins on government funding, but an alternative
      organization in New York City is showing how it can be done. It has developed a
      successful social entrepreneur program that employs HIV-infected clients, pays
      them living wages, and makes money from retail, food services, and medical care
      business entities, contributing three-quarters of the organization's revenues.

PMID- 15241859
TI  - Special report: a role model for ASOs. Making money the old-fashioned way. Retail
      enterprises hugely popular in NYC.
AB  - For those who doubt that a large AIDS service organization can succeed
      financially without big private or government grants, Housing Works Inc. is an
      example of how it can be done. About one-third of its money comes from its thrift
      shops, bookstore, and catering business.

PMID- 15241860
TI  - Special report: a role model for ASOs. One-stop shopping for client needs.
      Primary care is just the first step.
AB  - Housing Works Inc. fulfills a major part of its mission through three health care
      clinics, which provide a wide variety of health services. In addition to its
      primary care and mental health care for HIV/AIDS patients, the organization has
      developed some subspecialties and soon will expand those.

PMID- 15241861
TI  - Special report: a role model for ASOs. Myriad needs addressed under one huge
      umbrella. Even legal services are provided.
AB  - HIV/AIDS clients who seek help from Housing Works will find themselves enrolled
      in a holistic program that addresses many of their personal and social needs, as
      well as their medical needs.

PMID- 15241863
TI  - Drug in four countries meet U.S. standards.
AB  - Antiretroviral drugs from four developing countries have been found to meet
      United States Pharmacopoeia standards for the active drug amount listed on the
      label, according to a study in the May 1 Clinical Infectious Diseases.

PMID- 15241862
TI  - HIV-STD synergy worries public health officials. Drugs, Viagra play role in
      problem.
AB  - There is too little good news about sexually transmitted diseases (STDs) and
      sexual risk-taking behavior in the United States, and that continues to worry
      public health officials and HIV researchers.

PMID- 15241864
TI  - [Use of the Montezumae Baird frog in the biological diagnosis of the pregnancy.
      1949].

PMID- 15241865
TI  - Enzyme catalysis and engineering.

PMID- 15241866
TI  - Introduction to microbial catalysis and engineering.

PMID- 15241867
TI  - Bioprocessing, including separations.

PMID- 15241868
TI  - Biotechnology for fuels and chemicals--past, present, and future.

PMID- 15241869
TI  - Current awareness in prenatal diagnosis.

PMID- 15241870
TI  - Biobased industrial chemicals.

PMID- 15241871
TI  - Biomass pretreatment and hydrolysis.

PMID- 15241872
TI  - Plant biotechnology and feedstock genomics.

PMID- 15241873
TI  - Clinical practice guideline on treatment of acute apical abscess (AAA) in adults.

PMID- 15241874
TI  - The CCCD guidelines.

PMID- 15241875
TI  - Managed care's Crimea: medical necessity, therapeutic benefit, and the goals of
      administrative process in health insurance.

PMID- 15241876
TI  - State regulation of medical necessity: the case of weight-reduction surgery.

PMID- 15241878
TI  - What's the benefit? A new federal Medicare drug plan stimulates independent
      actions and new ideas, but what's the future role for states?

PMID- 15241877
TI  - Coverage conundrum: the challenge of rising state employee health insurance costs
      is hitting states hard.

PMID- 15241879
TI  - Exercising choices: living a health lifestyle can be a family affair--even in
      busy political families.

PMID- 15241880
TI  - Lactation consultant.

PMID- 15241881
TI  - Specialist in blood banking technology.

PMID- 15241882
TI  - Risk of receiving poor health care is significant in all parts of the United
      States.

PMID- 15241883
TI  - Following evidence-based prescribing guidelines for antihypertensives could save
      big bucks.

PMID- 15241884
TI  - U.S. outspends other nations, but health outcomes don't keep pace.

PMID- 15241885
TI  - Institute of Medicine rejects vaccine-autism link.

PMID- 15241886
TI  - [Living donors: solution to the organ shortage?].

PMID- 15241888
TI  - Pyranocoumarin(+/-)-4'-O-acetyl-3'-O-angeloyl-cis-khellactone induces
      mitochondrial-dependent apoptosis in HL-60 cells.
AB  - The pyranocoumarin (+)-4'-O-acetyl-3 'O-angeloyl-cis-khellactone (PC) isolated
      from Radix Peucedani (root of Peucedanum praeruptorum Dunn) showed a dose
      dependent effect at 10 -30 pg/mL on causing apoptotic DNA and nuclear
      fragmentations in HL-60 cells. After 24 h of PC treatment there were losses of
      mitochondrial membrane potential and cytochrome c. PC also increased total
      cellular and mitochondrial Bax protein, stimulated an increase in caspase
      dependent Bcl-2 cleavage but showed no effect on Bcl-Xv. These observations
      strongly suggest activation of the mitochondria apoptotic pathway. The pan
      specific caspase inhibitor, ZVAD-fmk, abolished the PC-induced apoptosis,whereas
      the caspase-8 inhibitor IETD-fmk showed no effect, implying the involvement of
      the caspase 9 pathway. PC caused a 2 to 12 hour transient increase in phospho
      ERK, and a 72 h-long activation of JNK. Pre-treatment with the MEK inhibitor
      PD98059, which suppresses ERK activation, paradoxically promoted PC-induced
      mitochondrial cytochrome c release, procaspase-3 and -8 cleavage, and enhanced
      apoptosis. Our results show that PC triggers mitochondria-mediated apoptosis in
      HL-60 cells, and the involvement of ERK and JNK signal pathways in the process.

PMID- 15241887
TI  - Clinical and mycological evaluation of therapeutic effectiveness of Solanum
      chrysotrichum standardized extract on patients with Pityriasis capitis
      (dandruff). A double blind and randomized clinical trial controlled with
      ketoconazole.
AB  - Dandruff (also called Pityriasis capitis) is a seborrhoeic dermatitis of the
      scalp. It has been correlated with the pathological colonization of the scalp
      with yeast from the genus Malassezia; this illness has a worldwide distribution
      and represents 25% of all scalp dermatosis cases. It has been demonstrated that
      the extract obtained from leaves of the plant Solanum chrysotrichum possesses
      biological activity against dermatophytes and yeast. Different steroidal saponins
      with antimycotic activity have been isolated from the active extract. Clinical
      trials with standardized extracts prepared with this vegetal species report high
      rates of clinical and mycological effectiveness in the treatment of Tinea
      pedis,without producing secondary effects. The aim of this randomized, double
      blind and controlled clinical study, was to compare the therapeutic effectiveness
      and tolerability of a shampoo containing a standardized extract of S.
      chrysotrichum (applied every third day, for 4 weeks), against 2% ketoconazole in
      the topical treatment of Pityriasis capitis. From a total of 120 patients with
      the clinical diagnosis of Pityriasis capitis, 14 subjects were eliminated because
      the presence of Malassezia was not proved, an-other two patients withdrew from
      the study due to non-medical causes and one more withdrew because Tinea capitis
      was diagnosed. Therefore, the final analysis included 51 subjects in the
      experimental group and 52 in the control; in 45.6% of the cases M. furfur was
      identified as the pathogenic agent, in 44.66% M. globosa was isolated, and 9.71 %
      of the patients had a mixed infestation. At the end of the treatment period, the
      prepared phytopharmaceutical with the standardized extract from S. chrysotrichum
      achieved a clinical effectiveness (total absence of signs and symptoms produced
      by Pityriasis capitis) of 92.16%;the mycological effectiveness (absence of
      Malassezia spp. in the direct examination and culture) was 68.63 %; whilst the
      tolerability (absence of side effects that prompt subjects to abandon the
      treatment) was 100%. The therapeutic success (clinical and mycological
      effectiveness plus tolerability) was 64.71%. The comparison of these results with
      that obtained from the group treated with 2% ketoconazole, showed no significant
      differences (Z2, p >0.23). These results show the therapeutic effectiveness and
      tolerability of the standardized extract from S. chrysotrichum on the local
      treatment of Pityriasis capitis associated with the yeast of the genus
      Malassezia.

PMID- 15241889
TI  - Anti-inflammatory activity of Leontopodium alpinum and its constituents.
AB  - The aerial parts and roots of Leontopodium alpinum Cass. (Asteraceae) were
      investigated for their in vivo topical anti-inflammatory activity using the
      inhibition of Croton oil-induced ear dermatitis in mice. For both of the plant
      parts, the dichloromethane extract induced a dose-dependent oedema reduction,
      being more active than the methanol and 70% aqueous methanol ex-tracts. Moreover,
      the dichloromethane extract of the aerial parts was more active than that of the
      roots (ID50 = 221 and 338 pg/cm2, respectively). Fatty acids make a significant
      contribution to the anti-oedema activity of the dichloromethane extract of the
      aerial parts, whereas bisabolane sesquiterpenes, tricyclic sesquiterpenes,
      coumarins and lignans are involved in the activity of the root extract. Two
      bisabolane derivatives reduced also the polymorphonuclear neutrophil leukocytes
      accumulation in the inflamed tissue, while a 7a-silphiperfol-5-ene type
      sesquiterpene and a coumarin derivative inhibited the in vitro chemotaxis of
      these inflammatory cells.

PMID- 15241890
TI  - Anti-inflammatory effect of kamebakaurin in in vivo animal models.
AB  - We have identified kamebakaurin as an inhibitor of NF-KB and elucidated its
      molecular mechanism as a specific inhibitor in the DNA-binding activity of the
      p50 subunit of NF-KB. Here, we describe its anti-inflammatory activity in in
      vitro and in vivo models. Kamebakaurin dose-dependently inhibited not only the
      expression of inflammatory NF-KB target genes such as iNOS,COX-2, and TNF-x, but
      also the production of PGE2 and TNF-a in LPS-stimulated RAW264.7 cells. Moreover,
      in an air pouch model of inflammation, it suppressed the recruitment of
      neutrophils,production of TNF-a as well as PGE2 in the pouch exudates induced by
      carrageenan. In addition, kamebakaurin dose-dependently suppressed the
      inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg
      kamebakaurin resulted in the 75% decrease of paw volume. Taken together,
      kamebakaurin, a specific inhibitor of DNA-binding activity of the p50 subunit, is
      a valuable candidate for the intervention in NF-KB-dependent pathological
      conditions such as inflammation.

PMID- 15241891
TI  - Cytotoxic epimeric withaphysalins from leaves of Acnistus arborescens.
AB  - Phytochemical analysis of the leaves of Acnistus arborescens (Solanaceae)
      resulted in the isolation of two new epimeric withaphysalins (17S,20R,22R)
      5beta,6beta: 18,20-diepoxy-4beta,18-dihydroxy-1-oxowitha-24-enolide (2, 18R and
      18S), together with the known withaphysalin F (1, 18R and 18S). Their structures
      were established by spectroscopic methods, including 2D NMR data and comparison
      with literature data. Compounds 1 and 2 dis-played potent cytotoxic activities
      against several cancer cell lines with IC50 values in the range of 0.20 to 1.46
      microg/mL for 1 and 0.89 to 8.08 microg/mL for 2. The strong cytotoxicity
      presented by 1 suggests that in this series of compounds, the 2,3-unsaturated
      ketone moiety is an important pharmacophoric unit. The cytotoxic activity seemed
      to be related to DNA synthesis inhibition, as revealed by the reduction of 5
      bromo-2'-deoxyuridine incorporation after 24 hours of incubation on leukemic
      cells.

PMID- 15241892
TI  - Antioxidant activity of saponins isolated from ivy: alpha-hederin, hederasaponin
      C, hederacolchiside-E and hederacolchiside-F.
AB  - The antioxidant activities of alpha-hederin and hederasaponin-C from Hedera
      helix, and hederacolchisides-E and -F from Hedera colchica were investigated, in
      this study. The antioxidant properties of the saponins were evaluated using
      different antioxidant tests: 1,1-di-phenyl-2-picryl-hydrazyl (DPPH.) free radical
      scavenging, total antioxidant activity, reducing power, superoxide anion radical
      scavenging, hydrogen peroxide scavenging, and metal chelating activities. Alpha
      hederin, hederasaponin-C, as well as hederacolchisides-E and -F exhibited a
      strong total antioxidant activity. At the concentration of 75 pg/mL, these
      saponins showed 94, 86, 88 and 75% inhibition on lipid peroxidation of linoleic
      acid emulsion,respectively. These various antioxidant activities were compared
      with model antioxidants such as a-tocopherol, butylated hydroxyanisole (BHA) and
      butylated hydroxytoluene (BHT).

PMID- 15241893
TI  - Platelet anti-aggregating triterpenoids from the leaves of Acanthopanax
      senticosus and the fruits of A. sessiliflorus.
AB  - Six triterpenoids, chiisanogenin, chiisanoside, ursolic acid, oleanolic acid,
      beta-sitosterol and daucosterol, were isolated as the platelet anti-aggregating
      components from the leaves of Acanthopanax senticosus and the fruits of A.
      sessiliflorus. Chiisanogenin showed about 50-fold higher potency than
      acetylsalicylic acid (ASA) on U46619-induced platelet aggregation (IC50o:6.21
      microM) and 10-20-fold higher effects than ASA on epinephrine- and arachidonic
      acid (AA)-induced aggregation (IC50:2.50 and 4.81 microM, respectively).

PMID- 15241894
TI  - In vitro anti-adhesive activity of an acidic polysaccharide from Panax ginseng on
      Porphyromonas gingivalis binding to erythrocytes.
AB  - A polysaccharide with high uronic acid content from the roots of Panax ginseng
      was found to inhibit the ability of Porphyromonas gingivalis to agglutinate
      erythrocytes. This polysaccharide showed a strong inhibitory activity (minimum
      inhibitory concentration 0.25 mg/mL), but treatment with pectinase resulted in
      non-inhibitory hydrolyzed products. In contrast, the inhibition by the acidic
      polysaccharide from the leaves of Artemisia capillaris was negligible. The
      carbohydrate composition of the two polysaccharides indicated that the anti
      adhesive activity may be correlated with glucuronic acid content, one of the
      components of glycosaminoglycans. Low molecular weight heparin and sucrose
      octasulfate revealed stronger inhibitory effects on bacterial binding, than the
      acidic polysaccharide from P. ginseng.

PMID- 15241895
TI  - When a trust chief exec came to blows with her SHA, something had to give.

PMID- 15241896
TI  - On location: Norfolk, Suffolk and Cambridgeshire. Star performer gets to grips
      with primary concerns.

PMID- 15241898
TI  - The HSJ barometer.

PMID- 15241897
TI  - Older people ideas. Down on your needs.

PMID- 15241899
TI  - Trustee profile. Susan West: faith in fate. Interview by Laurie Larson.

PMID- 15241900
TI  - Percutaneous intradiscal radiofrequency thermocoagulation for chronic discogenic
      low back pain.

PMID- 15241901
TI  - Transesophageal endoscopic treatments for gastroesophageal reflux disease.

PMID- 15241902
TI  - Effects of Crest Whitestrips bleaching on subsurface microhardness and
      ultrastructure of tooth enamel and coronal dentin.
AB  - PURPOSE: To describe the complementary subsurface analysis of structural and
      ultrastructural effects of bleaching with Crest Whitestrips on enamel and coronal
      dentin METHODS: Human tooth enamel specimens were cycled through a daily regimen
      including salivary immersions and treatments with commercial tooth whitening gels
      containing hydrogen peroxide or carbamide peroxide. Treatments with hydrogen
      peroxide in Crest Whitestrips gel base were carried out for up to 70 hours
      bleaching (some five fold to the clinical exposure required to produce
      satisfactory whitening in bleaching strip systems as established by double blind
      placebo controlled clinical studies) [correction]. Following in vitro laboratory
      cycling, the teeth were cross sectioned and remounted for observation of
      microhardness and ultrastructural characteristics in subsurface regions.
      Ultrastructure was assessed by application of confocal laser scanning microscopy
      (reflection mode). RESULTS: Peroxide whitening compositions had no effects on
      subsurface microhardness of enamel or dentin, even under conditions of five fold
      overbleaching. Crest Whitestrips gel containing up to 6.5% hydrogen peroxide
      applied for periods up to 70 hours (five kit) overbleaching was found to produce
      no changes (at a lateral resolution of 200-300 nm) in observed subsurface enamel
      and dentin ultrastructure or architecture.

PMID- 15241903
TI  - Influence of the pretreatment of occlusal pits and fissures on the retention of a
      fissure sealant.
AB  - PURPOSE: To evaluate different regimens of enamel conditioning on the retention
      of a pit and fissure sealant. METHODS: 100 extracted human molars were randomized
      into 10 experimental groups (n = 10). Conditioning of occlusal pits and fissures
      was performed with either 37% H3PO4, diamond bur and 37% H3PO4, Er:YAG laser,
      Er:YAG laser and 37% H3PO4, air abrasion (3 different settings), air abrasion (3
      different settings) and subsequent acid etching with 37% H3PO4. 24 hours after
      placing a compomer-based sealant, the specimens were artificially aged by
      thermocycling (5/55 degrees C; x1000) and immersed in basic fuchsin dye for
      another 24 hours. After sectioning, dye penetration along the enamel-resin
      interface was determined (% of the fissure depth). Data were statistically
      analyzed with Kruskal-Wallis H test and Mann-Whitney U test. For qualitative
      investigations, two further specimens of each group were analyzed in the SEM.
      RESULTS: Conventional acid etching resulted in significantly superior sealant
      retention than conditioning with either the Er:YAG laser or air abrasion
      (irrespective of particle size or air pressure). If mechanical conditioning of
      the laser or air abrasion was followed by acid-etching, results were
      statistically equal to the acid-etch only group.

PMID- 15241904
TI  - Clinical and radiographic evaluation of a resin-based root canal sealer.
AB  - PURPOSE: To conduct a preliminary clinical and radiographic evaluation of a resin
      based root canal sealer used in conjunction with gutta percha. METHODS: In a
      retrospective study on 180 patients who were seen for root canal therapy, a total
      of 295 root canals were treated with laterally condensed gutta-percha cones in
      conjunction with a methacrylate-based endodontic sealer (EndoRez). Root canal
      therapy had been carried out in one visit using standardized techniques. The
      results were assessed clinically and radiographically 14-24 months
      postoperatively and a comparison to baseline radiographs was made. 145 patient
      records were available for a follow-up examination. Success of root canal
      treatment was based on absence of clinical symptoms, a normal or slightly widened
      periodontal ligament and reduction of periapical radiolucencies with an absence
      of pain in patients that had pre-existing lesions associated with pain. RESULTS:
      The overall success rate was 913%. Root canals had been adequately filled to the
      working length in 110 teeth (75.7%), short from the working length in six cases
      (4.1%) and flush in 19 teeth (13.1%). Extruded sealer occurred in 10 (6.9%)
      instances. 49 teeth out of 55 (89.1%) that had preoperative apical radiolucencies
      revealed partial or total healing at the 14-24 months recall evaluation. 83 teeth
      out of 90 (92.2%), without preoperative radiolucencies, showed no radiographic
      changes. At the 14-24 months recall all patients reported being comfortable. 13
      (9.0%) cases were judged failures.

PMID- 15241905
TI  - Use of essential oil-containing mouthrinses by xerostomic individuals:
      determination of potential for oral mucosal irritation.
AB  - PURPOSE: To assess the irritation potential of an essential oil-containing
      mouthrinse (Listerine Antiseptic) in a population with objectively documented
      xerostomia (hyposalivation) using an exaggerated-exposure clinical model.
      METHODS: Following a baseline oral soft tissue examination, 19 qualifying female
      subjects with a mean age of 61 years and a mean unstimulated baseline salivary
      flow of 0.06 mL/min were randomly assigned either the essential oil mouthrinse or
      a negative control rinse. They rinsed under supervision with 20 ml of their
      assigned rinse for 30 seconds and 5 minutes later a second salivary flow rate was
      determined. They then rinsed unsupervised with 20 ml for 30 seconds three times
      daily for the next 14 days, and received soft tissue examinations on days 7 and
      14. After a 1-week interim period, subjects switched to the alternate rinse and
      the examination and rinsing regimens were repeated during the subsequent 2 weeks.
      RESULTS: The oral irritation potential of the essential oil mouthrinse was
      minimal. Oral mucosal abnormalities attributable to the test rinses were seen in
      only 2 subjects, both at the 7-day examination. These subjects were both using
      the essential oil mouthrinse. The abnormalities consisted of an asymptomatic
      "whitish slough" which was readily wiped off leaving a normal appearing, non
      erythematous mucosa. In both subjects, the oral mucosa appeared normal at the 14
      day examination.

PMID- 15241906
TI  - Durability of three simplified adhesive systems in Class V non-carious cervical
      dentin lesions.
AB  - PURPOSE: To investigate the durability of three simplified systems in Class V non
      carious abrasion/erosion lesions. METHODS: 144 non-carious cervical dentin
      lesions were restored either with Clearfil Liner Bond 2, a 2-step self-etching
      primer (n = 46), One Coat Bond, a one bottle total-etch system applied with one
      coat (n = 46), or Prompt-L-Pop, a 1-step self-etching primer ("all-in-one") (n =
      52), in 90 individuals. Ninety-eight of the lesions showed sclerotic dentin and
      46 were non-sclerotic. Sixty-one were slightly roughened with a diamond bur
      before conditioning. The restorations were evaluated every 6 months during a 2
      year period with slightly modified USPHS criteria. RESULTS: All except three
      restorations were evaluated over 2 years. The cumulative loss rates for Clearfil
      Liner Bond 2, One Coat Bond and Prompt-L-Pop were at 6 months: 4.3, 2.2 and 3.9%,
      at 18 months: 4.3, 10.9 and 15.4% and at 24 months: 8.7, 13.0 and 21.2%,
      respectively. The cumulative loss rates of the materials in sclerotic lesions
      (15.7%) versus non-sclerotic lesions (14.0%) were not significanty different.
      Restorations placed with a diamond bur-roughened lesions showed a loss rate of
      14.5%, while for the non-roughened lesions the frequency was 14.8%.

PMID- 15241907
TI  - Microleakage of cervical cavities restored with flowable composites.
AB  - PURPOSE: To investigate the microleakage of cervical cavities restored with
      flowable composites in conjunction with an all-in-one adhesive system (AQ Bond)
      and an experimental two-step self-etching primer system (ABF) after thermocycling
      or flexural load cycling. METHODS: 180 wedge-shaped cervical cavities on the
      labial surfaces of bovine incisors were treated with AQ Bond or ABF according to
      the manufacturers' instructions. The treated cavities were filled with one of
      three flowable composites (AElite Flo, Metafil Flo or Protect Liner F). Ten of 30
      specimens for each group were immersed in 0.5% basic fuchsin solution immediately
      after finishing of the restorations. Specimens to be subjected to thermocycling
      (5-60 degrees C, 15 seconds dwell time, 5000 cycles) or to flexural load cycling
      (approximately 0.5 mm labio-lingual displacement at the incisal edge, 10,000
      cycles, 1 Hz) prior to immersion in the dye were also prepared. After 24-hour
      storage in the dye solution, the teeth were sectioned longitudinally through the
      center of the restorations, and the degrees of dye penetration scored. The
      microleakage scores of a hybrid composite (Clearfil AP-X) obtained from our
      previous study were used for comparison. The data were analyzed with the Kruskal
      Wallis test and the Mann-Whitney U-test (P < 0.05). RESULTS: No significant
      differences in the microleakage patterns and scores were found among the flowable
      composites. On the other hand, significant differences in the microleakage
      patterns and scores were observed between the flowable and the hybrid composites.
      Thermocycling caused deterioration of marginal integrity, and the flowable
      composites showed more microleakage than the hybrid composite. In contrast,
      flexural load cycling did not cause deterioration of the marginal integrity when
      the cavities were filled with the flowable composites. Statistical analysis also
      revealed that the adhesive systems played a large role in the microleakage
      patterns.

PMID- 15241908
TI  - Effect of high intensity vs. soft-start halogen irradiation on light-cured resin
      based composites. Part II: Hardness and solubility.
AB  - PURPOSE: To determine hardness and solubility of light-cured resin-based
      composites after high intensity vs. soft-start quartz tungsten halogen
      irradiation. METHODS: Knoop hardness of resin-based composite specimens was
      measured at 1.5 mm depth after dry storage for 24 hours at 37 degrees C so as to
      indirectly evaluate degree of cure. Solubility was determined gravimetrically by
      extraction of post-cured (24 hours, 37 degrees C) specimens in 50 wt% methanol
      for 72 hours. Four hybrid (Filtek Z250, Herculite, Solitaire 2, Tetric Ceram), an
      inhomogeneously filled hybrid (InTen-S) and a microfilled (Filtek A110, formerly
      Silux Plus) composite were cured using the quartz tungsten halogen units Astralis
      10 and Optilux 501 in the high intensity (Astralis 10 High Power: 10 seconds @
      1300 mW/cm2; Optilux Boost: 10 seconds @ 1140 mW/cm2) or soft-start modes
      (Astralis 10 Pulse: increase to 700 mW/cm2 within 10 seconds, three periods of 2
      seconds @ 1300 mW/cm2 alternating with two periods of 2 seconds @ 700 mW/cm2;
      Optilux Ramp: exponential increase within 10 seconds, followed by 10 seconds @
      1140mW/cm2). RESULTS: For the fast curing composites Z250, Tetric Ceram and InTen
      S, equivalent hardness was observed after 10 seconds of high intensity and 20
      seconds of soft-start irradiation. For the slower curing composites Herculite,
      Solitaire 2 and A110, the soft-start protocols produced higher hardness values.
      Regarding solubility however, the superiority of soft-start irradiation was also
      seen for Tetric Ceram and InTen-S. The lowest solubility was observed for InTen
      S, followed by Z250, whereas Herculite and Solitaire 2 scored highest for this
      parameter.

PMID- 15241909
TI  - Durability of extensive Class II open-sandwich restorations with a resin-modified
      glass ionomer cement after 6 years.
AB  - PURPOSE: To evaluate the durability of a modified open-sandwich restoration
      utilizing a resin-modified glass ionomer cement (RMGIC) in large cavities.
      METHODS: 268, mostly extensive, Class II Vitremer/Z100 restorations were placed
      in 151 patients. 47% of the restorations were placed in patients considered as
      caries-risk patients. Six experimental groups, differing from each other in
      thickness of RMGIC layer and preconditioning, were evaluated at baseline and
      annually during 6-7 years according to modified USPHS criteria. RESULTS: After 6
      years, 220 restorations were evaluated. 42 failures (19%) were observed. The most
      frequent reasons for failure were material fracture (n = 11), tooth fractures (n
      = 9) and secondary caries (n = 10). Non-acceptable proximal dissolution of the
      RMGIC was seen in six restorations. Significantly more failures, but similar
      dissolution of the RMGIC, were recorded in high caries risk patients. No
      differences were seen between the experimental groups or between restorations
      with thick or thin RMGIC layer. 160 restorations were also evaluated at 7 years.
      Another 13 failures were observed, eight with non-acceptable dissolution, three
      secondary caries and two fractures. It can be concluded that the modified open
      sandwich restoration showed an acceptable durability for the extensive
      restorations evaluated. An accelerating dissolution of the RMGIC was observed at
      the end of the study.

PMID- 15241910
TI  - 4-year clinical performance and survival analysis of Class I and II compomer
      restorations in permanent teeth.
AB  - PURPOSE: To evaluate the 4-year clinical performance of the compomer Hytac in
      Class I and II cavities of permanent posterior teeth. METHODS: 53 compomer
      restorations were placed using the self-conditioning adhesive Hytac OSB (total
      bonding) without additional phosphoric acid-etching according to manufacturer's
      instructions. Restorations were rated (modified USPHS criteria) at baseline,
      after 6, 12, 18, 36 and 48 months in relation to tooth type (molar, premolar),
      size and class of cavities, isolation type (rubber dam, cotton rolls) and use of
      a calcium hydroxide liner. After 4 years, 39 restorations (73.6%) were available
      for examination. Statistical analysis was performed using Kaplan-Meier survival
      analysis with the logrank test and Fisher's exact test for the failure analysis.
      RESULTS: After 4 years, the success rate was 84.6%, six restorations failed
      (15.4%). The average annual failure rate was therefore 3.85%. Loss of marginal
      integrity was the main cause of restoration failure. The probability that a
      restoration would remain clinically acceptable after 4 years was calculated to be
      89% (Kaplan-Meier). No significant performance differences could be found between
      any of the restoration groups.

PMID- 15241911
TI  - Effect of ozone on the oral microbiota and clinical severity of primary root
      caries.
AB  - PURPOSE: To assess the effect of ozone on the microbial flora and clinical
      severity of primary root caries. METHODS: 26 patients with 70 primary root
      carious lesions (PRCLs) were entered. Each PRCL was classified in terms of color,
      cavitation, size, hardness, distance from the gingival margin and severity.
      Overlying plaque was then removed and each lesion dried. A biopsy was taken from
      half of each PRCL using a sterile excavator. Subsequently, the remaining lesions
      were exposed to ozone gas for a period of either 10 seconds (n = 35) or 20
      seconds (n = 35) and a further biopsy was taken. RESULTS: Using a paired Student
      t-test, a significant (P < 0.001) difference (mean +/- SE) in total micro
      organisms was observed in the ozone-treated samples after either a 10 seconds
      (log10 4.35 +/- 0.49) or 20 seconds (log10 0.46 +/- 0.26) ozone application
      compared with the control samples (log10 7.00 +/- 0.24) and (log10 6.00 +/- 0.21)
      respectively. Using Pearson's correlation tests, there were significant
      correlations for the reduction in total micro-organisms after 10 seconds of ozone
      application with cavitation, size, distance from gingival margin and severity of
      PRCLs (P < 0.05). In conclusion, ozone application either for 10 or 20 seconds
      dramatically reduced most of the micro-organisms in PRCLs without any side
      effects recorded at recall intervals between 3 and 5.5 months. Out of the 65
      PRCLs reviewed, 33 lesions had become hard, 27 lesions reversed to severity index
      1 from severity index 2, and five lesions remained the same following ozone
      application for a period of either 10 or 20 seconds.

PMID- 15241912
TI  - The scientific rationale and development of an optimized dentifrice for the
      treatment of dentin hypersensitivity.
AB  - PURPOSE: To describe the development of a new dentin hypersensitivity treatment,
      Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as
      the anti-hypersensitivity active agent. The objective was to develop a home-use
      hypersensitivity dentifrice that would be superior to the market leader,
      improving on what is available, which also contains 5% potassium nitrate as the
      anti-hypersensitivity active agent. METHODS: In vivo (clinicals, taste evaluation
      and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed
      volume, scanning electron microscopy, electron scanning chemical analysis and
      radioactive dentin abrasion) methods were performed. RESULTS: The objective was
      accomplished with the development of a new activated silica technology that
      resulted in enhanced potassium ion activity. In vitro documentation, supported by
      clinical studies, demonstrated that the resulting formula is more effective than
      the market leader for relief of hypersensitivity pain. Fast pain relief in less
      than 2 weeks and long-lasting protection against pain with regular use have also
      been clinically documented. Furthermore, FDA-required in vivo and in vitro
      studies indicate that this formula, which contains 0.45% stannous fluoride (1100
      ppm fluoride) as the anti-caries active agent, is effective against caries. Good
      taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical
      stability have all been engineered into this unique dentin hypersensitivity
      treatment. In summary, a highly efficacious consumer friendly treatment for
      dentin hypersensitivity has been developed.

PMID- 15241913
TI  - Strategic planning. Part V of the dental management pyramid series.
AB  - Strategic planning is not something that should be taken lightly. It is the
      course by which you will map out your own personal future, as well as that of
      your practice. You cannot look ahead until you and your dental team are ready to
      accurately and responsibly assess the strengths, weaknesses, opportunities and
      threats facing your practice today. Putting in the work to do so will leave you
      and your practice in a better position to grow and prosper in the long run.

PMID- 15241914
TI  - Chemical composition of the essential oils of Clausena lansium from Hainan
      Island, China.
AB  - The essential oils of wild Clausena lansium collected in Hainan Island, China
      were extracted from leaves, flowers, sarcocarps and seeds, and then analyzed by
      using GC/MS. The main constituents of the essential oils were: beta-santalol
      (35.2%), bisabolol (13.7%), methyl santalol (6.9%), ledol (6.5%) and sinensal
      (5.6%) in the leaves; beta-santalol (50.6%), 9-octadecenamide (17.2%) and
      sinensal (4.1%) in the flowers; beta-santalol (52.0%), alpha-santalol (15.5%),
      farnesol (5.2%) and sinensal (4.0%) in the sarcocarps; and phellandrene (54.8%),
      limonene (23.6%), and p-menth-1-en-4-ol (7.5%) in the seeds.

PMID- 15241915
TI  - Chemical composition of the essential oils of two Alpinia species from Hainan
      Island, China.
AB  - The essential oils of two Alpinia species, ie. A. hainanensis and A. katsumadai,
      from Hainan Island, China were analyzed by using GC-MS. The major constituents in
      the leaf oil of A. hainanensis were ocimene (27.4%), beta-pinene (10.1%), 9
      octadecenoic acid (6.5%), n-hexadecanoic acid (5.8%), 9,12-octadecadienoic acid
      (5.4%), and terpinen (4.3%). The oil constituents obtained from the flowers of A.
      hainanensis were ocimene (39.8%), beta-pinene (17.7%), terpinene (5.5%), p-menth
      1-en-ol (4.9%), caryophyllene (4.9%), and phellandrene (4.4%). In A. katsumadai,
      the major constituents in the leaf oil were p-menth-1-en-ol (22.0%), terpinen
      (19.0%), 4-carene (9.1%), 1,8-cineole (8.3%), and camphor (5.6%). The major
      constituents in the flower oil were p-menth-1-en-ol (21.3%), 1,8-cineole (20.2%),
      terpinen (12.6%), phellandrene (7.0%), 4-carene (6.4%), and beta-pinene (5.2%).

PMID- 15241916
TI  - Terpenoids from Anthemis austriaca Jacq.
AB  - The aerial parts of Anthemis austriaca Jacq. afforded five new sesquiterpene
      lactones (two of which are dimeric guaianolides) and three new guaiane type
      sesquiterpene acids In addition, seven known terpenoids were also found in the
      studied species. Their structures were elucidated by spectral methods.

PMID- 15241917
TI  - Volatile oil composition of the aerial parts of Ajuga orientalis L. from Iran.
AB  - The volatile oil content and composition of the aerial parts of Ajuga orientalis
      L. (Lamiaceae) grown in northern parts of Iran have been analyzed by GC/MS.
      Thirty compounds were identified, representing 97.9% of the total oil. The main
      compounds were germacrene-D (24.2%), beta-cubebene (18.3%), beta-caryophyllene
      (16.9%) and alpha-cubebene (5.3%).

PMID- 15241918
TI  - Volatile components of some Rutaceae species.
AB  - The volatile components of the aerial parts of Ruta graveolens and Haplophyllum
      suaveolens, as well as of leaves of Zanthoxylum limoncello, Z. panamense and Z.
      setulosum have been studied by GC/MS analysis.

PMID- 15241919
TI  - Volatile constituents of the flower and fruit oils of Pittosporum tobira (Thunb.)
      Ait. grown in Iran.
AB  - The volatile components of the flower and fruit oils from Pittosporum tobira
      (Thunb.) Ait. grown in Iran, obtained through hydrodistillation, were analyzed by
      GC/MS. Sixteen compounds (representing 90.7% of the oil) and seventeen
      constituents (representing 89.9% of the oil) were identified in the flower and
      fruit oils, respectively. While the flower oil contained a-pinene (38.6%), n
      nonane (11.8%), (E)-nerolidol (9.0%) and (E)-beta-ocimene (7.7%), the fruit oil
      contained a-pinene (30.2%), n-nonane (12.2%), germacrene-D (12.0%), a-cubebene
      (7.6%) and beta-cubebene (5.1%) as the main compounds.

PMID- 15241920
TI  - Contents of 1,4-benzoxazin-3-ones and 2-benzoxazolinone from Stenandrium dulce
      (Nees).
AB  - Secondary metabolites, DIBOA, HBOA, 7-OH-HBOA and BOA, were isolated and
      quantified from S. dulce (Nees), a native species in Chile belonging to the
      Acanthaceae family. The highest DIBOA and HBOA contents were determined in leaves
      (9.25 mmol kg(-1) fr. wt) and root (6.81 mmol kg(-1) fr. wt), respectively.
      Aglycones, 7-OH-HBOA and HBOA, were isolated together from root extracts of
      Acanthaceae species. Both, HBOA and 7-OH-HBOA should be direct precursors in the
      biosynthesis of DIBOA and DIMBOA, respectively.

PMID- 15241921
TI  - Tetraenol, a novel sesquiterpenoid from the relict plant Tetraena mongolica in
      China.
AB  - A novel furansesquiterpenoid, tetraenol, was isolated from a relict shrub plant,
      Tetraena mongolica, collected from the northern desert of the Ningxia Hui
      Autonomous Region. The structure of the new compound was elucidated on the basis
      of spectroscopic analysis.

PMID- 15241923
TI  - Thymus fontanesii Boiss. & Reut.--A potential source of thymol-rich essential oil
      in North Africa.
AB  - The waterdistilled essential oil from dried aerial parts of one of the Algerian
      thymes, Thymus fontanesii Boiss. & Reut. grown in Setif province, Algeria, was
      analyzed by GC/MS. Fifteen components were characterized representing 99.4% of
      the total components detected. The major components of the oil were thymol
      (67.8%), gamma-terpinene (15.9%) and p-cymene (13.0%).

PMID- 15241922
TI  - Comparison of tropane alkaloid spectra between Datura innoxia grown in Egypt and
      Bulgaria.
AB  - The alkaloid spectra of Datura innoxia plants grown in Egypt and Bulgaria were
      investigated by GC-MS. Thirty-eight alkaloids were detected in the roots, leaves
      and fruits of the plants. Five new alkaloids for D. innoxia are reported.
      Alkaloid spectra of Egyptian and Bulgarian plants differ significantly in respect
      to their alkaloid composition and main alkaloids accumulated in the plant organs.

PMID- 15241924
TI  - Alkyl- and alkenylresorcinols of wheat grains and their chemotaxonomic
      significance.
AB  - Resorcinolic lipid contents and homologue compositions in extracts isolated from
      soft winter, soft spring and hard (durum) wheat grains were evaluated by both
      instrumental and chromatography means. Resorcinol concentrations determined in
      wheat were diverse and varied in samples harvested within two consecutive
      vegetative years, whereas their homologue profiles were found to be rather
      invariable. The predominant alkylresorcinols identified in wheat grains were
      saturated 1,3-dihydroxy-5-n-heneicosylbenzene and 1,3-dihydroxy-5-n
      nonadecylbenzene. 1,3-Dihydroxy-5-n-heptadecylbenzene and 1,3-dihydroxy-5-n
      tricosylbenzene were also determined, whereas 1,3-dihydroxy-5-n-pentadecylbenzene
      and 1,3-dihydroxy-5-n-pentacosylbenzene were present in these extracts only in
      spurious amounts. Furthermore, our results show that alk(en)ylresorcinols may be
      useful as chemotaxonomic markers for a distinction between soft and hard wheat
      plants. Cluster analysis with Ward's amalgamation algorithm and five different
      distance linkage types clearly discriminated particular wheats into species- and
      cultivar-specific clusters, whereas the use of principal component analysis
      allowed us to specify, which of the variables analysed were decisive. This
      approach may be useful for both plant breeders and taxonomists to classify wheat
      species/cultivars.

PMID- 15241925
TI  - Coumarin content and physicochemical profile of Mikania laevigata extracts.
AB  - The 'guaco' lianous herb Mikania laevigata, which is widespread in Southern
      Brazil, is traditionally used to treat bronchitis, asthma and cough. This work
      investigates the influence of the extraction method, solvent:drug ratio, ethanol
      proportion, harvest season (summer or winter) and solvent heating on the
      physicochemical profile of the extracts (dry weight, density, pH) and the
      coumarin (1,2-benzopyrone) content determined by LC. Among the results obtained,
      it is observed that higher ethanol content increases the amount of coumarin in
      the extract. Leaves harvested in summer also produce an extract with a high
      coumarin yield. The most efficient method of extraction is percolation,
      independent of the solvent used.

PMID- 15241926
TI  - Biotransformation of isoprenoids and shikimic acid derivatives by a vegetable
      enzymatic system.
AB  - In biotransformations carried out under similar conditions enzymatic systems from
      carrot (Daucus carota L.), celeriac (Apium graveolens L. var. rapaceum) and horse
      radish (Armoracia lapathifolia Gilib.) hydrolyzed the ester bonds of acetates of
      phenols or alicyclic alcohols. Nevertheless, methyl esters of aromatic acids did
      not undergo hydrolysis. Alcohols were oxidized to ketones in a reversible
      reaction.

PMID- 15241927
TI  - Enhanced hydrocarbon biodegradation by a newly isolated Bacillus subtilis strain.
AB  - The relation between hydrocarbon degradation and biosurfactant (rhamnolipid)
      production by a new Bacillus subtilis 22BN strain was investigated. The strain
      was isolated for its capacity to utilize n-hexadecane and naphthalene and at the
      same time to produce surface-active compound at high concentrations (1.5 - 2.0 g
      l(-1)). Biosurfactant production was detected by surface tension lowering and
      emulsifying activity. The strain is a good degrader of both hydrocarbons used
      with degradability of 98.3 +/- 1% and 75 +/- 2% for n-hexadecane and naphthalene,
      respectively. Measurement of cell hydrophobicity showed that the combination of
      slightly soluble substrate and rhamnolipid developed higher hydrophobicity
      correlated with increased utilization of both hydrocarbon substrates. To our
      knowledge, this is the first report of Bacillus subtilis strain that degrades
      hydrophobic compounds and at the same time produces rhamnolipid biosurfactant.

PMID- 15241928
TI  - Microbial transformations of alpha-santonin.
AB  - Fungal biotransformations of alpha-santonin (1) were conducted with Mucor
      plumbeus (ATCC 4740), Cunninghamella bainieri (ATCC 9244), Cunninghamella
      echinulata (ATCC 9245), Curvularia lunata (ATCC 12017) and Rhizopus stolonifer
      (ATCC 10404). Rhizopus stolonifer (ATCC 10404) metabolized compound 1 to afford
      3,4-epoxy-alpha-santonin (2) and 4,5-dihydro-alpha-santonin (3) while
      Cunninghamella bainieri (ATCC 9244), Cunninghamella echinulata (ATCC 9245) and
      Mucor plumbeus (ATCC 4740) were capable of metabolizing compound 1 to give a
      reported metabolite, 1,2-dihydro-alpha-santonin (4). The structures of these
      transformed metabolites were established with the aid of extensive spectroscopic
      studies. These fungi regiospecifically reduced the carbon-carbon double bond in
      ring A of alpha-santonin.

PMID- 15241929
TI  - Biotransformation of 3alpha,4alpha-dihydroxy-dihydro-beta-agarofuran by Rhizopus
      nigricans.
AB  - 3alpha,4alpha-Dihydroxy-dihydro-beta-agarofuran (1), prepared from (+)
      dihydrocarvone by a traditional synthetic method, the Robinson annelation, was
      biotransformed by R. nigricans to afford a new metabolite characterized as
      1alpha,3alpha,4alpha-trihydroxy-dihydro-beta-agarofuran (2) by spectroscopic
      method. An acetylated derivative was prepared.

PMID- 15241930
TI  - 4-Hydroxykigelin and 6-demethylkigelin, root growth promoters, produced by
      Aspergillus terreus.
AB  - Root growth promoters, 4-hydroxykigelin (1) and 6-demethylkigelin (2), together
      with 6-hydroxymellein (3) were isolated from cultures of the fungus Aspergillus
      terreus and their structures were identified by spectroscopic analysis. The
      biological activities of the three dihydroisocoumarins, 1, 2, and 3, have been
      examined using a bioassay method with lettuce seedlings. Furthermore,
      interactions between the dihydroisocoumarins and indole-3-acetic acid against the
      root growth have been examined.

PMID- 15241931
TI  - Malate accumulation in different organs of Mesembryanthemum crystallinum L.
      following age-dependent or salinity-triggered CAM metabolism.
AB  - Different organs of Mesembryanthemum crystallinum exhibit differing levels of CAM
      (Crassulacean acid metabolism), identifiable by quantification of nocturnal
      malate accumulation. Shoots and also basal parts of young leaves were observed to
      accumulate high concentrations of malate. It was typically found in mature leaves
      and especially prominent in plants subjected to salt stress. Small amount of
      nocturnal malate accumulation was found in roots of M. crystallinum plants
      following age-dependent or salinity-triggered CAM. This is an indication that
      malate can be also stored in non-photosynthetic tissue. Measurements of catalase
      activity did not produce evidence of the correlation between activity of this
      enzyme and the level of malate accumulation in different organs of M.
      crystallinum although catalase activity also appeared to be dependent on the
      photoperiod. In all material collected at dusk catalase activity was greater than
      it was observed in the organs harvested at dawn.

PMID- 15241932
TI  - Seasonal variation of kaurenoic acid, a hypoglycemic diterpene present in Wedelia
      paludosa (Acmela brasiliensis) (Asteraceae).
AB  - We evaluated the variation of the concentration of kaurenoic acid (1), which is a
      bioactive diterpene, in leaves, flowers, stems and roots from Wedelia paludosa
      (Acmela brasiliensis) for different seasons using the HRGC/FID method. The
      results indicated that the concentration of 1 is higher in the roots and stems
      during the autumn. The pharmacological results suggested that kaurenoic acid is
      responsible, at least in part, for the hypoglycemic potential detected in this
      plant.

PMID- 15241933
TI  - Anti-ulcerogenic lignans from Taxus baccata L.
AB  - Four lignan type compounds, lariciresinol, taxiresinol, isolariciresinol and 3
      demethyl-iso-lariciresinol, were isolated from the heartwood of Taxus baccata L.
      (Taxaceae) growing in Turkey through chromatographic techniques. In vivo anti
      ulcerogenic potency of these compounds was investigated on ethanol-induced
      ulcerogenesis model in rats at two different doses, 50 and 100 mg/kg. All
      compounds were shown to possess significant anti-ulcerogenic activity at both
      doses. However, the effect of taxiresinol was the most prominent.

PMID- 15241934
TI  - Anti-inflammatory constituents of Mortonia greggii Gray.
AB  - A new phytochemical study of Mortonia greggii (Celastraceae) afforded four
      friedelan derivatives (1-4), three lupanes (5-7), retusine (8), two esterified
      polyhydroxyagarofurans (9-10), mortonin C (11) and photomortonin C (12). The anti
      inflammatory activity on carrageenan and 12-O-tetradecanoylphorbol-13-acetate
      induced models of inflammation, as well as the ability to inhibit the nitric
      oxide (NO) produced by lipopolysaccharide-stimulated mouse peritoneal macrophages
      were evaluated for the main metabolites. Our results showed that the friedelan
      dehydrocanophyllic acid methyl ester (1) exhibits an anti-inflammatory effect
      which could be related to an inhibition of prostaglandin and NO production. The
      activity of lupeol (5), 29-hydroxylupeol (6) and 29-hydroxylupenone (7) might be
      involved with the prostanoid synthesis. The presence of the hydroxy groups in 6
      appears to be important for activity. The edema inhibition capacity of retusine
      (8) could be related to a reduction of the prostaglandin production. The
      agarofuran derivative 10 is an NO inhibitor whose activity is probably not
      involved in the synthesis of prostaglandins.

PMID- 15241935
TI  - Oxygenated bisabolane fucosides from Carthamus lanatus L.
AB  - The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated
      bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D
      fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10
      hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9
      diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol
      beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and
      stigmasterol 3-O-beta-D-glucoside. Asperuloside appears to be the second
      representative of the iridoid monoterpene group found in the plant family
      Asteraceae, which until recently was considered to lack iridoids. The main
      constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic
      activities.

PMID- 15241936
TI  - The antimicrobial activity of extracts of the lichen Cladonia foliacea and its (
      )-usnic acid, atranorin, and fumarprotocetraric acid constituents.
AB  - The antimicrobial activity of the chloroform, diethyl ether, acetone, petroleum
      ether, and ethanol extracts of the lichen Cladonia foliacea and its (-)-usnic
      acid, atranorin, and fumarprotocetraric acid constituents against 9 bacteria and
      fungi has been investigated. The extracts and pure compounds alone were found
      active against the same bacteria and the same yeasts. Bacillus cereus, Bacillus
      subtilis, Staphylococcus aureus, Streptococcus faecalis, Proteus vulgaris,
      Listeria monocytogenes, Aeromonas hydrophila, Candida albicans, and Candida
      glabrata growth were inhibited. In addition, the MICs of the extracts, (-)-usnic
      acid, atranorin and fumarprotocetraric acid were determined.

PMID- 15241937
TI  - Wulfenia carinthiaca Jacq., antioxidant and pharmacological activities.
AB  - Relative antioxidant activities of a methanolic extract of three phenylpropanoid
      glycosides and three iridoid glycosides from Wulfenia carinthiaca were evaluated
      using the Briggs-Rauscher (BR) reaction method. This method is based on the
      inhibitory effects by antioxidants on oscillations of the BR reaction. The total
      extract showed a certain antioxidant activity with respect to resorcinol chosen
      as standard. The three phenylpropanoid glycosides showed a very high relative
      antioxidant activity while iridoid glycosides had practically no activity. These
      experimental results were confirmed by empirical calculations based on the BDE
      (Bond Dissociation Enthalpy) theory. The total phenolic content was also measured
      for the phenylpropanoid glycosides using the Folin-Ciocalteu reagent. The
      obtained values as gallic acid equivalents were in perfect agreement with the
      relative antioxidant activities. From a pharmacological point of view the results
      obtained demonstrate that the methanolic extract of W. carinthiaca have
      antinociceptive and antiedematogenic effects in the different models adopted. The
      plant extract produced a significant inhibition, dose related, of the rat paw
      edema induced by carrageenin. The anti-inflammatory activity is probably due to
      the phenylpropanoid compounds present in the plant. The histological sections of
      paw tissue in animals treated with Wulfenia carinthiaca extract confirmed the
      anti-inflammatory effects. The results of the antinociceptive assay indicated a
      significant reduction on the number of abdominal writhes of mice, induced by
      acetic acid.

PMID- 15241938
TI  - Analysis of the labial gland secretions of the male bumble bee Bombus perplexus
      Cresson (Hymenoptera: Apidae) from North America.
AB  - The labial gland secretions from males of the bumble bee Bombus (Pyrobombus)
      perplexus Cresson were analysed by gas chromatography/mass spectrometry (GC/MS)
      in the electron impact and positive ion chemical ionization mode. The major
      compound of the complex mixture of alkenols, alkenals, fatty acids, hydrocarbons,
      wax type esters and steroids is 3,7,11,15-tetramethyl-2,6,10-hexadecatrien-1-ol
      (geranylcitronellol), considerable amounts of hexadecan-1-ol and Z-9-hexadecen-1
      ol were also found. All alcohols were present as esters of the detected acids. In
      older samples both the acids and the alcohols sometimes could not be detected in
      the GC; therefore, the possibility to check the detected acid-alcohol pattern by
      interpreting the wax type ester peaks is very instructive. Moreover, the labial
      gland contains a rich mixture of mono- and di-unsaturated straight chain
      hydrocarbons. The similarity in composition of the labial glands of the North
      American B. (Pyrobombus) perplexus with the Eurasian species B. (Pyrobombus)
      hypnorum corroborates the assumption that the two species are conspecific. The
      likely supposition that the hydrocarbons could play an essential role in the
      chemical communication in bumble bees is discussed.

PMID- 15241939
TI  - Collagen from diamondback squid (Thysanoteuthis rhombus) outer skin.
AB  - Collagens (acid-solubilized and pepsin-solubilized collagens) were prepared from
      diamondback squid outer skin and partially characterized. The yields of acid
      solubilized and pepsin-solubilized collagens were about 1.3 and 35.6%,
      respectively, on a dry weight basis. Pepsin-solubilized collagen was heterotrimer
      with a chain composition of ala2a3. The patterns of peptide fragments were
      different from that of porcine skin collagen. Denaturation temperature was 27.5
      degrees C, about 10 degrees C lower than that of porcine collagen. The amino acid
      composition of pepsin-solubilized collagen from diamondback squid outer skin was
      similar to that from cuttlefish outer skin. This squid is big among squid
      species, and its skin is thick. It is clear that diamondback squid outer skin has
      a potential as an alternative source of collagen to bovine skin and bone. At
      present, collagen using aquatic materials such as skin (cod and a deep-sea fish)
      and scale (sea bream and anchovy) is the development stage in the related
      industries. Unless the problem of BSE infection in land animals is resolved
      aquatic materials as an alternative source of collagen will attract much
      attention in the cosmetic and medical fields.

PMID- 15241941
TI  - Contribution of disulfide bonds and calcium to Molluscan hemocyanin stability.
AB  - Disulfide bonds and calcium ions contribute significantly to the stability of the
      hemocyanin from the mollusc Rapana thomasiana grosse (gastropod). An extremely
      powerful protective effect of Ca2+ at a concentration of 100 mM (100% protection)
      against the destructive effect of reductants like dithiothreitol was observed.
      This is important for the practical application of molluscan hemocyanins in
      experimental biochemistry, immunology and medicine. The reduction of the
      disulfide bonds in the Rapana hemocyanin leads to a 20% decrease of the a-helical
      structure. The S-S bonds contribute significantly to the free energy of
      stabilization in water increasing delta G(D)H2O by 6.9 kJ mol (-1) The data are
      related to the X-ray model of the Rapana hemocyanin functional unit RtH2e. The
      results of this study can be of common validity for related respiratory proteins
      because the cysteine residues are conserved in all sequences of molluscan
      hemocyanins published so far.

PMID- 15241940
TI  - Stress causes tissue-specific changes in the sialyltransferase activity.
AB  - Numerous pathological conditions are associated with specific changes in
      glycosylation. Recent studies clearly demonstrated a link between stress and the
      development and course of many diseases. Biochemical mechanisms that link stress
      and diseases are still not fully understood, but there are some indications that
      changes in glycosylation are involved in this process. Influence of acute and
      chronic psychological stress on protein sialylation as well as the activity of
      sialyltransferases, enzymes that synthesize sialoglycoproteins, has been studied
      on Fischer rats. Liver, spleen, kidney, skeletal muscle, heart, adrenal gland,
      serum, cerebellum, hippocampus, medulla oblongata and cortex have been analyzed.
      Statistically significant tissue- and type of stress-specific changes in total
      sialyltransferase (ST) activity were observed. Acute stress resulted in 39%
      increase of ST activity in liver and spleen, while at the same time there was 43%
      decrease in ST activity in cerebellum. In chronic stress, ST activity increased
      in spleen (93%) and decreased in liver (17%), cerebellum (38%) and hippocampus
      (64%). Western-blot analysis using Maackia amurensis and Sambucus nigra lectins
      did not reveal any difference in protein sialylation. The results of serum
      corticosterone analysis indicate that showed increase in acute stress and
      decrease in chronic stress are in good accordance with the hypothesis that
      corticosterone has a role in the regulation of liver ST activity.

PMID- 15241942
TI  - Optimization of a chemical attractant for Epicometis (Tropinota) hirta Poda.
AB  - In field trapping tests in Hungary cinnamyl alcohol (3-phenyl-2-propen-l-ol) and
      transanethole [(1-methoxy-4-(1-propenyl)benzene)] attracted significantly more
      adult Epicometis (Tropinota) hirta (Coleoptera, Scarabaeidae, Cetoniinae) when
      presented together in the same bait compared to the single compounds Best
      attraction was recorded by a 1:1 mixture. Addition of other common floral scent
      compounds, ie. 3-methyl eugenol, 4-methoxy-cinnamaldehyde, anisylacetone, beta
      ionone, cinnamyl acetate, cinnamic aldehyde, eugenol, indole, 2-phenylethanol or
      phenylacetaldehyde did not influence catches. The binary cinnamyl alcohol/trans
      anethole bait described in this study is recommended for use in traps of E. hirta
      for agricultural purposes.

PMID- 15241943
TI  - Half-inhibition concentrations of new cholinesterase inhibitors.
AB  - The power of chosen carbamates and hydrazinium derivatives (carbazates) to
      inhibit the hydrolysis of acetylthiocholine by butyrylcholinesterase or
      acetylcholinesterase was tested. The determined pI50 values (= negative logarithm
      of the molar concentration inhibiting the enzyme activity by 50%) of the tested
      substances were compared with pI50 values of the commercially used drugs for the
      Alzheimer's disease treatment--rivastigmine and galanthamine.

PMID- 15241944
TI  - Delayed reproductive death and ROS levels in the progeny of irradiated melanoma
      cells.
AB  - The cell death and survival of proliferating (clonogenic) cells were investigated
      in two human melanoma cell lines to assess the optimal conditions for preparation
      of apoptotic bodies from melanoma cells. After 50 J/m2 UVB+UVC the maximal levels
      of apoptotic cells assayed by Trypan blue staining, nucleosomal DNA
      fragmentation, MTT, and TUNEL tests were observed within 2-3 d of radiation. In
      100 Gy gamma-irradiated cultures these apoptosis indicators were delayed for up
      to 3 weeks. In addition, clonogenic cells were observed only in exponentially
      growing cultures irradiated with UV at high cell density but not in gamma
      irradiated cultures. The response of melanoma cultures after high UV radiation
      doses contrasted to the response in lethally gamma-irradiated cultures. UV
      irradiated melanoma cultures were recovered within two weeks. Most of the
      clonogenic cells in the recovered colonies contained micronuclei. ROS levels
      determined by DCF fluorescence and a modified MTT test were also normalized
      obviously due to the extensive antioxidant defense system of melanoma cells. UV
      radiation of tumor cells might be the preferential method for preparation of
      apoptotic bodies. The presence of clonogenic cells in the suspension of apoptotic
      bodies from melanoma cells used for pulsing of dendritic cells with tumor
      antigens might compromise this protocol for preparation of cell vaccines.

PMID- 15241945
TI  - Antifungal activity of oosporein from an antagonistic fungus against Phytophthora
      infestans.
AB  - An antifungal metabolite, oosporein, was isolated from the culture of
      Verticillium psalliotae that produced the antagonistic effects on Phytophthora
      infestans. Oosporein exhibited a significant growth-inhibitory effect on P.
      infestans in comparison with other phytopathogenic fungi.

PMID- 15241946
TI  - CEO IT Achievement Award. Targeting quality. Hastings sees IT as mighty weapon to
      improve care.

PMID- 15241947
TI  - CEO IT Achievement Award. Pulling it together. Pelham's leadership put Trinity at
      cutting edge.

PMID- 15241948
TI  - CEO IT Achievement Award. IT at your service. Schaeffer sees unified data system
      as a key solution.

PMID- 15241949
TI  - CEO IT Achievement Award: nominees.

PMID- 15241950
TI  - A concise history of management hooey.

PMID- 15241951
TI  - Lilly goes off Prozac.

PMID- 15241952
TI  - Champions of profitable growth.
AB  - Many companies have posted impressive top-line growth over the past two decades
      in their respective economic regions--for instance, Wal-Mart in North America, BP
      in Europe, Toyota in Asia, and News Corporation in the Southern Hemisphere. But
      which were the best at converting all of that revenue growth into shareholder
      value? Harvard Business Review asked C. Bennett Stewart III, the senior partner
      of the consulting firm Stern Stewart & Company, and his colleagues to come up
      with the answer. For the period 1983 to 2003, they assembled a list of the top 20
      high-growth value adders (and laggards) in each of the four regions cited above.
      Their calculations gave equal weight to companies' revenue growth and market
      value-added scores, revealing the important effect of region on the performance
      of companies in the same industry. For instance, while automakers are positioned
      high on the Asian list of high-growth value adders, U.S. carmakers GM and Ford-
      each of which reported revenue growth in excess of 100 billion dollars between
      1983 and 2003--are among the value laggards on the North American list, as are
      DaimlerChrysler and Volkswagen on the European list. The Japanese win through
      better efficiency, higher quality, and narrower product mixes, the author says.
      And while there are four telecom companies represented among the European high
      growth value adders, there are none on the North American list. That's probably
      because the European telecoms enjoyed more protective regulation, made fewer high
      priced acquisitions, and didn't bet as big on the overblown dot-com economy, the
      author says.

PMID- 15241953
TI  - A time for growth: an interview with Amgen CEO Kevin Sharer. Interview by Paul
      Hemp.
AB  - Fast growth is a nice problem to have--but a hard one to manage well. In this
      interview, Kevin Sharer, the CEO of biotech giant Amgen, talks about the special
      challenges leaders face when their companies are on a roll. Sharer, who was also
      head of marketing at pre-WorldCom MCI and a division head and a staff assistant
      to Jack Welch at GE, offers insights drawn from his own experience--and from his
      own self-proclaimed blunders: "I learned the hard way that you need to become
      credible and enlist support inside the company before you start trying to be a
      change agent. If you think you're going to make change happen simply by force of
      personality or position or intellect, you'd better think again." And change there
      was: Under Sharer's leadership, Amgen overhauled its management team, altered its
      culture, and launched a couple of blockbuster products. How do chief executives
      survive in that kind of dizzying environment? "A CEO must always be switching
      between different altitudes--tasks of different levels of abstraction and
      specificity," Sharer says. "You might need to spend time working on a redesign of
      your organizational structure and then quickly switch to drafting a memo to all
      employees aimed at reinforcing one of the company's values." Having a supportive
      and capable top team is also key: "A top management team is the most revealing
      window into a CEO's style, values, and aspirations.... If you don't have the
      right top team, you won't have the right tiers below them. [The] A players won't
      work for B players. Maybe with a company like GE, the reputation of the company
      is so strong that it can attract top people to work for weaker managers. In a new
      company like Amgen, that won't happen."

PMID- 15241954
TI  - Funding growth in an age of austerity.
AB  - Everyone knows that corporate growth--true growth, not just agglomeration-
      springs from innovation. And the common wisdom is that companies must spend
      lavishly on R&D if they are to innovate at all. But in these fiscally cautious
      times, where every line item of every budget in every company is under intense
      scrutiny, many organizations are doing just the opposite. They tighten their
      belts, subject nascent product-development programs to rigorous screening, and
      train R&D staffers to think in business terms so the researchers will be better
      able to decide whether an idea for a product or service is worth pursuing in the
      first place. Such efficiency measures are commendable, say authors Gary Hamel and
      Gary Getz. But frugality is not a growth strategy, they point out, and, in truth,
      there is very little correlation between corporate performance and the amount
      spent on innovation. Companies like Southwest, Cemex, and Shell Chemicals have
      shown that businesses don't have to spend a fortune on R&D to reap the benefits
      of innovation. To produce more growth per dollar invested, companies must produce
      more innovation per dollar invested. Hamel and Getz explain how businesses can
      dramatically improve their innovation yields. They offer these five imperatives:
      Increase the number of innovators among existing employees (whatever their job
      titles) by involving them in innovation processes and events. Focus on developing
      truly radical ideas--ones that change customers' expectations and behaviors and
      industry economics--not just incremental ideas. Look for innovation sources
      outside the organization, as well as inside. Increase the learning from small,
      low-risk experiments. And commit to long-term, consistent development efforts.

PMID- 15241955
TI  - Darwin and the demon: innovating within established enterprises.
AB  - As commercial processes commoditize in a developed economy, they are outsourced
      or transferred offshore, leaving onshore companies with unrelenting, Darwinian
      pressure to come up with the next wave of innovation. But innovation is a broad
      term. There are many types, from the ballyhooed disruptive innovation to more
      mundane forms such as process and experiential, which might involve,
      respectively, doing such things as streamlining the supply chain and delighting
      customers with small modifications of products. Many executives find it hard to
      decide which kind to focus on. The best way to choose is to consider the phases
      of a market's life span. In a market's earliest phase, a new technology attracts
      enthusiasts and visionaries. Eventually, the market reaches the Main Street
      section of its life, when growth slows, flattens, and finally subsides. Different
      types of innovation produce more bang for the buck at different points in the
      life cycle. Disruptive innovation, for example, is rewarded most during the
      earliest phase. Once the life cycle advances to Main Street, however, the
      marketplace is no longer willing to yield the revenue or margin gains necessary
      to fund that type of innovation, so other forms, including process and
      experiential, yield better returns. But attempts to change the company's
      direction are often thwarted by the inertia that success creates. To overcome the
      inertia demon, managers must introduce new types of innovation while aggressively
      extracting resources from legacy processes and organizations. By running the two
      efforts in parallel, they can defeat the demon and renew the company.

PMID- 15241956
TI  - Selling to the moneyed masses.
AB  - Over the past decade, the distribution of household incomes has shifted so much
      that a much larger proportion of consumers now earn significantly higher-than
      average incomes--while still falling short of being truly rich. As a result, what
      used to be a no-man's-land for new product introductions has in many categories
      become an extremely profitable "new middle ground." How can marketers capitalize
      on this new territory? The key, say the authors, is to rethink the positioning
      and design of offerings and the ways they can be brought to market. Take, for
      instance, how Procter & Gamble redefined the positioning map for tooth-whitening
      solutions. A decade ago, dental centers were popularizing expensive bleaching
      techniques that put the price of a professionally brightened smile in the 400
      dollars range. At the low end, consumers also had the choice of whitening
      toothpastes that cost anywhere from 2 dollars to 8 dollars. P&G wisely positioned
      itself between the two ends, successfully targeting the new mass market with its
      35 dollars Whitestrips. In product categories where it's clear the middle ground
      has already been populated, it's important for companies to design or redesign
      offerings to compete. An example is the Polo shirt. How do you sell a man yet
      another one after he's bought every color he wants? Add some features, and call
      it a golf shirt. Here, marketers have introduced designs based on the concept of
      "occasional use" in order to stand out. Finally, companies wishing to reach the
      "almost rich" can change how they go to market. Perhaps no mass retailer has made
      a stronger bid for the mass affluent than Target Stores, which has pioneered a
      focus the company itself characterizes as upscale discount. The strategy has made
      Target an everyday shopping phenomenon among well-heeled urbanites and prosperous
      professionals.

PMID- 15241958
TI  - Getting the most out of all your customers.
AB  - Companies spend billions of dollars on direct marketing, targeting individual
      customers with ever more accuracy. Yet despite the power of the myriad data
      collecting and analytical tools at their disposal, they're still having trouble
      optimizing their direct-marketing investments. Many marketers try to minimize
      costs by pursuing only those customers who are cheap to find and cheap to keep.
      Others try to get the most customers they possibly can and keep all of them for
      as long as they can. But a customer need not be loyal to be highly profitable,
      and many loyal customers turn out to be highly unprofitable. Companies can get
      more out of direct marketing if they see it as a single system for generating
      profits than if they try to maximize performance measures at each stage of the
      process. This article describes a tool for doing just that. Called ARPRO
      (Allocating Resources for Profits), the tool is essentially a complex regression
      analysis that can estimate the impact of a company's direct-marketing investments
      on the profitability of its customer pool. With data that companies already
      gather, the tool can show managers how much to spend on acquisition versus
      retention and even what percentage of their funds they should allocate to the
      different direct-marketing channels. Using the model, companies can easily see
      that even small deviations from the optimal levels of customer profitability are
      expensive. Applying it to one catalog retailer showed, for instance, that a 10%
      reduction in marketing costs would lead to a 1.8 million dollar drop in long-term
      customer profits. Conversely, spending 69% less on marketing would actually
      increase average customer profitability at one B2B service provider by 42%.
      What's more, the tool can show that finding the optimal balance between
      investments in acquisition and retention can be more important than finding the
      optimum amount to invest overall.

PMID- 15241957
TI  - When to ally & when to acquire.
AB  - Acquisitions and alliances are two pillars of growth strategy. But most
      businesses don't treat the two as alternative mechanisms for attaining goals.
      Consequently, companies take over firms they should have collaborated with, and
      vice versa, and make a mess of both acquisitions and alliances. It's easy to see
      why companies don't weigh the relative merits and demerits of acquisitions and
      alliances before choosing horses for courses. The two strategies differ in many
      ways: Acquisition deals are competitive, based on market prices, and risky;
      alliances are cooperative, negotiated, and not so risky. Companies habitually
      deploy acquisitions to increase scale or cut costs and use partnerships to enter
      new markets, customer segments, and regions. Moreover, a company's initial
      experiences often turn into blinders. If the firm pulls off an alliance or two,
      it tends to enter into alliances even when circumstances demand acquisitions.
      Organizational barriers also stand in the way. In many companies, an M&A group,
      which reports to the finance head, handles acquisitions, while a separate
      business development unit looks after alliances. The two teams work out of
      different locations, jealously guard turf, and, in effect, prevent companies from
      comparing the advantages and disadvantages of the strategies. But companies could
      improve their results, the authors argue, if they compared the two strategies to
      determine which is best suited to the situation at hand. Firms such as Cisco that
      use acquisitions and alliances appropriately grow faster than rivals do. The
      authors provide a framework to help organizations systematically decide between
      acquisition and alliance by analyzing three sets of factors: the resources and
      synergies they desire, the marketplace they compete in, and their competencies at
      collaborating.

PMID- 15241959
TI  - How CEOs manage growth agendas.
AB  - When does it make sense for companies to grow from within? When is it better to
      gain new capabilities or access to markets by merging with or acquiring other
      companies? When should you sacrifice the bottom line in order to nurture the top
      line? In a thought-provoking series of essays, five executives--Kenneth Freeman
      of Quest Diagnostics, George Nolen of Siemens USA, John Tyson of Tyson Foods,
      Kenneth Lewis of Bank of America, and Robert Creifeld of Nasdaq--describe how
      they have approached top-line growth in various leadership roles throughout their
      careers. They write candidly about their struggles and successes along the way,
      relaying growth strategies as diverse as the companies and industries they
      represent. The leaders' different tactics have almost everything to do with their
      companies' particular strengths, weaknesses, and needs. Freeman, for instance,
      emphasizes the importance of knowing when to put on the brakes. When he first
      became CEO of Quest, he froze acquisitions for a few years so the company could
      focus on internal processes and "earn the right to grow." But for Greifeld, it's
      all about innovation, which "shakes up competitive stasis and propels even mature
      businesses forward." The executives agree, though, that companies can grow (and
      can do so profitably) by distinguishing their offerings from those of other
      organizations. As Ranjay Gulati of Northwestern's Kellogg School of Management
      points out in his introduction to the essays, no matter what strategies are in
      play,"it's important to remember that growth comes in many forms and takes
      patience.... The key is to be ready to act on whatever types of opportunities
      arise."

PMID- 15241960
TI  - [The health care system in France and Germany].
AB  - The two countries have adopted the Bismarckian scheme for the organization and
      financing of their health care. In particular, the medical doctors are paid on a
      fee-for-service basis, by the sickness funds of which financial resources come
      from compulsory contributions of employers and employees. Nowadays, France and
      Germany are different as concerns a large number of features but they are facing
      similar challenges: * the health expenditures are steadily rising and threatening
      the equilibrium of all the national economy * since 1980, if not earlier, the two
      countries have experienced physician surplus: in France, a system of numerus
      clausus was imposed upon student intake since the early 70's; in Germany, in
      1992, a system of geographical numerus clausus was imposed upon setting up new
      medical practices * as a result, but for different reasons, each country is now
      slowly entering an era of physician shortage * during the last two decades, each
      country has tried to implement various reforms but, so far, the results are not
      convincing.

PMID- 15241961
TI  - [A comprehensive professional evaluation of the program Obesity in French
      Polynesia].
AB  - A professional evaluation of the program of the fight against obesity set up by
      the French Polynesian Health Board for a five-year period was carried out in
      2001. A comprehensive evaluation was favoured so that adjustments could be better
      established. Its principle is based on qualitative analysis of the speech of the
      27 actors belonging to all levels of intervention and decision in the program. It
      aims to highlight the convergences and the deviations between what the program
      produced on the socio-cultural environment and their institutional or
      professional references. Semi-directive interviews were carried out. The results
      highlighted a state of uncertainty in the management of human, financial and
      material resources linked to the political context--awarding the necessary means
      for implementing the program remains unpredictable. A lack of human resources,
      problems of collaborating with other sectors, shortcoming skills, and structures
      around a methodology and forecast indicators were identified. The objectives
      (media campaigns, improvement in medical practice, and adaptation of a healthy
      and balanced food environment) were partially carried out. After a year and a
      half, the most remarkable result is finally that obesity problem is recognised as
      a public health priority by the population, professionals and decision-makers.

PMID- 15241962
TI  - [Integrating general practice through the "territoralization" of the health
      system in Italy].

PMID- 15241963
TI  - Latvia's health care system on the move.

PMID- 15241964
TI  - [Aging of population and medical workforce: a prospective view of health care
      provision in France in the year 2025].
AB  - In 2011, the first generations of the French baby-boom will reach their 65th
      anniversary. In the same year the first cohorts of the French medical "graduate
      boom" (doctors graduated during the boom period 1974-1994) will reach their
      retirement age. From 2010 to 2025, French population will increase 4% but the
      French elderly will increase 40%. Depending on medical student intake policy
      adopted today, the French medical profession will decrease slowly or drastically.
      But the most striking feature of the period will be the aging of the medical
      workforce. Doctors aged 55 years and over will be between 42% and 47% of the
      medical workforce in 2025, as compared to 41% in 2010 and 14% in 2000. A great
      amount of factors--of which the demographic ones--will contribute to raise the
      demand for health care in the two coming decades. On the other side, the
      demographic change undergone by the medical profession (decrease of the total
      number, increase of the aged doctors, increase of the female doctors...) will
      decrease the amount of supply. However, the first problem facing the country is
      not how to raise the amount of supply but how to finance the forthcoming sharp
      growth of demand. The problem is not specific to France, as pointed out in a
      paper drafted twenty years ago.

PMID- 15241965
TI  - A classical live attenuated vaccine for sheep pox.
AB  - A classical live attenuated sheep pox vaccine was prepared using the Ranipet
      strain of sheep pox virus (SPV) at the 50th passage in a secondary lamb
      testicular cell system. The TCID50 and RD50 were 10(9.63)/ml and 10(9.51)/ml.
      respectively. The SID50 of SPV challenge virus was 10(5)/ml. The vaccine was
      found to have no adverse effects in laboratory animals, and was safe and
      effective in SPV seronegative lambs. In the field, 660 sheep were vaccinated with
      an immunizing dose containing 1 x 10(2) TCID50. Randomly selected vaccinated
      sheep mounted good cell-mediated immunity and humoral responses as measured by
      glucose utilization test and serum neutralization test, respectively, for the
      study period of 6 months.

PMID- 15241966
TI  - A descriptive study of urban rabies during the civil war in Sierra Leone: 1995
      2001.
AB  - A study was conducted to assess the effects of the breakdown in internal
      infrastructure on the incidence of canine-transmitted human rabies in urban areas
      of Sierra Leone during the course of the civil war between 1995 and 2001. Data
      from provincial hospitals in the Western Area and Southern Province indicated
      that there was a significant increase in the incidence of canine-transmitted
      urban human rabies chi2 = 39.63, p < 0.0001, particularly among children chi2 =
      23.73, p < 0.0001, over the course of the war. In the Western Area in 2001,
      towards the end of the war, there was a significant increase in adult cases,
      which was reflected in the observed versus the expected chi2 ratio (70 versus
      53). Interview-based questionnaire surveys in Freetown administered between 2001
      and 2002 indicated that dogs were commonly kept for security reasons, and were
      largely unrestrained and unlicensed, regardless of the socioeconomic status of
      the owner. Virtually all dogs were unvaccinated and were mainly living in close
      proximity with humans. This study indicated that there is an urgent requirement
      for appropriate mass rabies vaccination campaigns for pet dogs and for campaigns
      to manipulate the urban habitat to control free-roaming and wandering but owned
      dog populations in Freetown and other urban areas in the provinces of Sierra
      Leone. Interview-based questionnaires administered in three districts of Freetown
      indicated a relatively high degree of uniformity in dog husbandry and veterinary
      care habits across a wide range of socioeconomic status categories in dog owners.

PMID- 15241967
TI  - A slaughter slab survey for extra-intestinal porcine helminth infections in
      northern Tanzania.
AB  - A survey on extra-intestinal porcine helminths was conducted at three slaughter
      slabs that receive pigs from Mbulu, a district endemic for porcine cysticercosis
      in northern Tanzania. Seventy carcases of pigs between 1 and 2 years old were
      examined between December 1997 and March 1998. The examination involved ante
      mortem lingual examination for Taenia solium cysticercosis followed by post
      mortem inspection. In addition, a laboratory procedure was performed to determine
      whether any of these domestic pigs were infected with Trichinella species.
      Parasites detected were Ascaris suum (44.3%), Echinococcus granulosus (4.3%) and
      Taenia hydatigena (1.4%). The lack of cases of porcine cysticercosis in this
      study compared to previous studies suggests that pig traders are conducting their
      own ante-mortem lingual examinations before purchasing pigs in the rural
      communities where the parasite is still highly prevalent. It is concluded that
      improved meat inspection could prove useful in reducing the local population's
      risk of infection with these parasites. The results of this study have revealed
      the parasites of agricultral and public health importance in the targeted
      communities. Further epidemiological investigations are required to better
      determine parasite prevalence and impact in order to formulate appropriate and
      cost-effective strategies for control.

PMID- 15241968
TI  - Theileria parva: in vitro studies on the effects of holding temperature, pH and
      medium on sporozoite infectivity.
AB  - The effects of holding temperature, pH and medium on the infectivity of Theileria
      parva sporozoites were investigated using an in vitro infectivity assay. The
      sporozoite infectivity lasted for 72 h at a holding temperature of 4 C but for
      only 24 h at 24 degrees C. Sporozoite infectivity was found to be sensitive to pH
      variations and sporozoites were most infective between pH 7 and pH 8. There was a
      significant loss in infectivity at pH 5 and infectivity was almost totally
      abolished at pH 9. Theileria parva sporozoites are usually held and manipulated
      in Eagle's minimum essential medium (MEM) with Earles' salts. In this study.
      Leibovitz-15 supplemented with 15% fetal bovine serum gave a significantly better
      infectivity than Eagle's MEM (3.8 log units versus 1.0 log units) or any other
      medium. The importance of proper management of the T. parva sporozoite
      environment in the laboratory or field is emphasized by the findings in these
      studies and might also explain some of the failures of vaccination when the pH of
      the holding medium was allowed to deteriorate.

PMID- 15241969
TI  - Risk factors for kid mortality in West African Dwarf goats under an intensive
      management system in Ghana.
AB  - Breeding records from 1997 to 2000 for West African Dwarf goats kept under an
      intensive management system on the National Breeding Station at Kintampo in Ghana
      were analysed for the effect on mortality of sex, season and type of birth, and
      birth weight. The pre-weaning and post-weaning mortalities were 10% (n = 390) and
      23.1% (n = 351), respectively, while the overall mortality from birth up to 12
      months of age was 30.8% (n = 390). The post-weaning period recorded significantly
      higher proportions of deaths in males, females, single-born and twins, during the
      rainy and dry seasons, and for kids with low or high birth weight, compared to
      the pre-weaning period. There was significantly higher mortality in male kids
      than in female kids. The odds and risks of death for male kids were about twice
      those for females at post-weaning and up to 1 year of age. At pre-weaning and up
      to 1 year of age, a higher proportion of the dead were twins. Twins had
      approximately 2.5 the risk of death at pre-weaning, compared to singles. Also,
      kids born in the rainy season had significantly higher mortality than those born
      in the dry season. Kids that died by the time of weaning were significantly
      lighter in weight at birth than those that survived. Male kids had significantly
      higher mean weights at birth and at weaning, but not at 12 months of age. The
      significance of these findings is discussed.

PMID- 15241970
TI  - The mineral scoring technique and evaluation of indigenous browse species as
      natural mineral phytocentres for goats in African rangelands.
AB  - The utilization and evaluation of indigenous browse species as natural mineral
      phytocentres for goats was examined by the combined use of mineral
      concentrations, mineral scores, browse accessibility and abundance in the Ankole
      rangeland, Uganda. The species Grewia bicolor and Carissa edulis with > 140%
      mineral scores and > 70% accessibility were the most valuable mineral
      phytocentres and were the victims of overgrazing. Acacia albida and Acacia
      abyssinica with > 130% mineral scores but < 30% browse accessibility were
      valuable for the cut-and-carry feeding system. Species mineral scores at average
      and maximum dietary recommendations were < 60%, highlighting the mineral
      insufficiency of range browse for high-performance goats. Mineral supply
      potential was highest (35.0%) in the genus Acacia and lowest (5.3%) in
      Dichrostachsys. Browse accessibility was < 35%, in 69.2% of species. Acacia
      hockii was the most abundant species (24.5%) but had the lowest mineral score
      (17.7%). Browse species (90-100%) were deficient in Fe, Mn, Cu and Zn. The
      combined use of mineral concentrations and mineral scoring technique was superior
      to the use of mineral concentrations alone in defining mineral adequacy,
      deficiency and supply potential, making the mineral scoring technique a valuable
      tool in browse management.

PMID- 15241971
TI  - Decline in assayable progesterone in bovine serum under different storage
      conditions.

PMID- 15241972
TI  - Effects of cottonseed cake-based diets supplemented with blood meal, alone or
      with lysine, on the growth of pigs.
AB  - An experiment was carried out to establish the effect on the growth of pigs of
      including blood meal or lysine in diets containing gossypol from cottonseed cake.
      Forty Landrace x Large White pigs (20 of each sex) were randomly allocated to 5
      treatments of 8 pigs each in a 2 x 2 factorial design with two levels of lysine
      or two levels of blood meal in the diets plus a control diet. The pigs were fed
      different diets and slaughtered at 75.0 +/- 2.0 kg live weight for carcase
      analysis. Supplementing the diets with blood meal resulted in higher live weight
      gains (p<0.001) and improved feed conversion ratios (p<0.001) than supplementing
      with lysine. Pigs fed the higher level of cottonseed cake showed a significant
      (p<0.001) depression in live weight gain and feed conversion ratio compared to
      those fed a low level of the cake. There was no significant difference (p>0.05)
      in intake in the pigs fed diets with cottonseed cake including blood meal or
      synthetic lysine. The kidney and liver weights of the pigs fed the diets with a
      higher level of cottonseed cake were significantly greater (p<0.001) than in
      those fed the lower level, but when the diets containing cottonseed cake were
      supplemented with blood meal or lysine at the same level there was no significant
      difference (p>0.05) in the weights of these organs. Lysine or other factors
      derived from blood meal appear to be more efficient than synthetic lysine in
      reducing the adverse effects of gossypol.

PMID- 15241974
TI  - Nutritional requirement of adult donkeys (Equus asinus) during work and rest.

PMID- 15241973
TI  - An outbreak of Marek's disease in chickens in central Ethiopia.
AB  - A study was conducted on an outbreak of Marek's disease in a commercial poultry
      farm containing 8500 chickens in central Ethiopia. On repeated visits, farm and
      flock history was collected, sick birds were examined and clinical signs and
      daily mortality were recorded. A total of 80 (27 sick and 53 dead) birds 12-22
      weeks old, were collected, autopsied and examined. The mortality rate was 46% for
      the first 14 weeks of the outbreak. Acute and chronic (classical) forms of the
      disease, the respective occurrence of which varied significantly (p<0.01) in
      young (14.6% vs 85.4%) and adults (48.7% vs 51.31%) were manifested. All the
      autopsied birds had gross and microscopic lesions indicative of Marek's disease
      in the peripheral nerve(s) and/or visceral organs. Lesions involving peripheral
      nerves and visceral lymphomas were recorded mainly in adults (28/35, 80%) and
      young birds (34/45, 75%), respectively. These differences in the two age groups
      were statistically significant (p<0.01). Young birds seem to be highly
      susceptible to the acute disease. Poor management, overstocking and lack of
      vaccination might have favoured the outbreak. Marek's disease causes considerable
      economic loss and is a major threat to poultry production in Ethiopia. This
      report emphasizes that Marek's disease should be considered as a disease of
      economic significance in chicken production in Ethiopia and warrants due
      attention.

PMID- 15241975
TI  - Kosovo and beyond--military trauma.

PMID- 15241976
TI  - Mitchiner Memorial Lecture 1999.

PMID- 15241977
TI  - The approach to a major incident.
AB  - Any major incident will test the organisational and medical skills of those
      involved. The best response can only be achieved with good planning and
      preparation, and the adoption of a structured approach to the scene. A clear
      chain of command should exist within all emergency services and must be followed.
      The Ambulance and Medical Incident officers take overall responsibility for the
      health service response. Management priorities--Command and Control, Safety,
      Communications, Assessment--must take precedence over support priorities--Triage,
      Treatment, Transport.

PMID- 15241978
TI  - Gulf related illness--current perspectives.
AB  - In the years after Operation Desert Storm and Operation Granby, some 4-8% of
      veterans of the conflict began to report symptoms of illness. Common complaints
      included fatigue, impaired cognition, joint pain, sleep disturbances, and chest
      pains. Between 1992 and 1994 in the USA, and later in the UK, governments set up
      medical assessment programmes to define the scope of the problem in qualitative
      and quantitative terms. Initial efforts moved to extensive epidemiological
      assessment and a search for causative mechanisms of what became termed "Gulf War
      Syndrome". Eventually significant sums of money were invested in medical and
      investigative research in an attempt to relate symptoms to causes. This paper
      presents the historical background and context to the problem of Gulf and war
      related illnesses, summarises the findings of relevant epidemiological studies
      and discusses some of the hypotheses that have been generated to explain the
      clusters of symptoms reported by veterans. Finally, the current UK research
      programme and its underlying rationale is presented. The aim is to provide an
      overview of the current position and assist in the interpretation of a
      diagnostically difficult area.

PMID- 15241979
TI  - The Omagh bombing--a medical perspective.
AB  - The bomb in Omagh on the 15th August 1998 was responsible for the largest loss of
      life of any single terrorist incident in the whole of the "Troubles" in Northern
      Ireland. However, the medical response to this tragedy provided an excellent
      opportunity for the civilian and military agencies to work together. As a
      consequence of this a number of lessons were drawn which are presented in the
      paper. Whatever the outcome of the peace process these lessons will have an
      important role in the future, since history would suggest that there is little
      possibility of the terrorist threat ever completely.

PMID- 15241980
TI  - Night vision goggles, human factors aspects--a questionnaire survey of helicopter
      aircrew.
AB  - Night vision goggles have become an essential component of military aviation.
      They provide superior visual capability over unaided night vision, but there are
      several inherent limitations associated with human factors and systems
      limitations. This study used a questionnaire survey of Army helicopter aircrew to
      investigate the incidence of human factors problems which continued after NVG
      use, with particular reference to visual problems and neck discomfort. It also
      looked at hardware interaction problems, such as cockpit lighting, and other
      aspects of NVG use, such as training and aircrew concerns. The issues are
      described and analysed, and areas of concern, which may have bearings on
      operational effectiveness and/or safety, have been highlighted.

PMID- 15241981
TI  - Analysis of out of hours telephone consultation at the medical reception station
      Sennelager, British Forces Germany.
AB  - The advent of 'NHS Direct', has centred attention on nurses giving telephone
      advice as part of the provision of out of hours medical care. A three month
      retrospective study of telephone consultations by nurses at the MRS Sennelager
      showed that telephone consultation greatly contributes to "out of hours" medical
      care. The outcome of telephone consultations made out of hours revealed that in
      70% of telephone calls the advice given enables the patient to stay at home.
      Twenty eight percent of patient contact out of hours was by telephone.

PMID- 15241982
TI  - Evidence based problem solving in general practice: the foreign body in the nose.
AB  - This paper reviews the efficacy of six different methods of removal of foreign
      bodies from the nose. Removal with a Fogarty catheter, the Ambu Bag method,
      nebulised adrenaline, tissue adhesive, forceps and direct suction are considered.
      No method appears to be obviously superior to any other.

PMID- 15241984
TI  - Hepatic abscesses as the primary presentation of Crohn's disease.
AB  - Hepatic Abscesses have been reported in association with Crohn's disease (CD).
      They either occur as a complication of known CD, or as in this case, are the
      presentation of undiagnosed disease. The management of the CD associated with
      liver abscesses is a matter of debate. We report a case of CD presenting with
      hepatic abscesses, review the literature and discuss the management options.

PMID- 15241985
TI  - Pre-hospital care: the trapped patient.

PMID- 15241983
TI  - Medico-legal issues surrounding medical countermeasures used in the Gulf War-
      part 1.
AB  - When the multinational force deployed to the Gulf after Iraq's invasion of Kuwait
      in 1990, military intelligence assessed the Iraqi's as possessing and being
      capable of using weapons of mass destruction. There was judged to be a real
      threat that chemical weapons, especially nerve agents, and certain biological
      weapons would be used. Coalition countries attempted to reduce the effects by the
      use of medical countermeasures. Since the Gulf conflict a series of medico legal
      problems from this policy have arisen; some of which have formed the basis of
      claims against MOD. In this paper I shall review how consent to treatment may
      have been modified in the military operational context and by the interface with
      military law. I shall look at the issues of clinical negligence and how duty of
      care may be affected. In the next article I shall look at relevant employment
      law; briefly review how medicines regulatory provision applies to medical
      countermeasures, whether they were properly licensed and whether in any case this
      applied to the Ministry of Defence in the context of deployment to the Gulf War.

PMID- 15241986
TI  - Accident and emergency medicine.

PMID- 15241987
TI  - Battlefield first aid.

PMID- 15241988
TI  - The influence of military surgeons in the development of vascular surgery.

PMID- 15241989
TI  - Reflections on the relationship between the led and the leader.

PMID- 15241990
TI  - PBL a fad or reality?

PMID- 15241991
TI  - Description of a Canadian PBL programme in pharmacology.

PMID- 15241992
TI  - Core concepts in biochemistry and molecular biology in an integrated MBBS
      curriculum.

PMID- 15241993
TI  - Health-related millennium development goals: policy challenges for Pakistan.
AB  - OBJECTIVES: There are two objectives: (a) to clearly articulate the Millennium
      Development Goals (MDGs) adopted by the United Nations in 2000 and their
      implications for developing countries like Pakistan; and (b) to critically review
      the challenges faced by Pakistan in achieving the health-related MDGs. METHODS: A
      critical review of secondary data and information generated primarily by
      multilateral agencies and United Nations organizations. RESULTS: The MDGs
      represent a global consensus on the broad goals of development to be achieved by
      2015. Of the eight Millennium Development Goals, three are specifically health
      related--reducing infant (under-5) and maternal mortality; and combating
      HIV/AIDS, tuberculosis, malaria and other significant communicable diseases.
      According to various studies, many developing countries will not achieve the MDGs
      without concerted efforts and commitment of additional resources. Like many other
      developing countries, Pakistan is also faced with an enormous challenge in
      reaching the Millennium Development Goals and targets set by the United Nations.
      For Pakistan, perhaps the most challenging MDG is that of reducing "by three
      quarters the maternal mortality ratio." Maternal mortality is so intertwined with
      other "social" factors--including the status of women--that a comprehensive
      holistic approach is required. CONCLUSION: In order to achieve the MDGs, Pakistan
      would require a fundamental shift in its policy and strategic directions. Along
      with allocation of significant additional resources for health, it needs to
      review and reprioritize the use of existing resources, focusing more on primary
      health care. Pakistan must also adopt a holistic integrated approach that views
      health, education, and other social sector development as intrinsically
      interrelated and interwoven. Without such an integrated approach, achieving the
      health-related MDGs is likely to remain illusive for Pakistan. There is a
      critical need to foster a healthy debate on the health-related Millennium
      Development Goals in Pakistan so as to inform and, hopefully influence, public
      policy.

PMID- 15241994
TI  - Facilitating inter-spousal communication for birth spacing--a feasibility study
      of Pakistani couples for policy implications.
AB  - OBJECTIVE: To test three practices introduced to couples for adaptation of a non
      permanent modern method of family planning and the role that each partner played
      during the process. SETTING: Urban and sub-urban areas of Karachi, Lahore, and
      Quetta. METHODS: 'Behavioral trials' was conducted which is a formative research
      method in which researcher and participants negotiate behavior(s) that the
      participant agrees to try for a specific amount of time. Interviews were
      conducted on 72 married couples (144 men and women) living in urban and sub-urban
      areas of Karachi, Lahore and Quetta. Study participants were either non-users of
      modern methods of family panning, or using traditional methods. The three
      behaviors negotiated were: a) Discuss benefits of birth spacing with spouse; b)
      discuss specific methods of family planning and decide on the most appropriate
      one and c) initiate use of a modern temporary method of family planning. RESULTS:
      After the introduction of first practice, of 72 couples 38 reported failure to
      initiate the discussion with their spouse. Where women initiated the discussion
      the response from spouse was not as favorable as where men initiated the
      discussion. After introduction of second practice 28 couples were successful in
      discussing about selection of a family planning method. Twenty-four couples
      finally selected and used a method. Traditional users were more likely to adopt a
      modern method than non-users, especially those with 3-5 children. CONCLUSION:
      Strategies to cultivate a culture of inter-spousal communication on use of family
      planning methods should be developed as a component of family planning programs.

PMID- 15241995
TI  - Prescription and dispensing practices in public sector health facilities in
      Pakistan: survey report.
AB  - OBJECTIVES: To gather information on existing prescription practices, dispensing
      practices and patient satisfaction in government health services of the NWFP,
      Baluchistan and Punjab province. METHODS: A cross sectional study design was used
      for this purpose. Ten health care facilities were selected from each province
      keeping appropriate representation from first level health facilities, district
      health facilities and tertiary care hospital. Analysis of selected indicators was
      carried out on the basis of provinces, health facilities, gender and different
      age groups. RESULTS: Documentation of 914 responses was completed from three
      provinces. Almost equal distribution of encounters was maintained representing
      different health facilities. Forty seven percent of encounters involved children
      under 15 years of age. Female patients comprised of 56% and the mean age of the
      entire sample was 26 years. The mean dispensing time was only 38 seconds, the
      mean consultation time was 1.79 minutes and the average number of drugs per
      prescription turned out to be 2.7 out of which only 1.6 drugs were being
      dispensed from the facility. More than half of the prescriptions contained
      antibiotics and 15% of patients were prescribed with injectables. Only half of
      the patients expressed satisfaction with their visit to health facility.
      CONCLUSIONS: Like many other developing countries, prescription and dispensing
      practices are not satisfactory in public sector health facilities of Pakistan.
      Appropriate and workable solutions need to be developed and implemented in the
      country to improve systems. Regular audits and qualitative studies should become
      part of the effort.

PMID- 15241996
TI  - Census survey for a primary health care programme.
AB  - OBJECTIVE: To describe the process of gathering information from a census survey
      as a preliminary step for supporting the working of a primary health care center.
      It also presents briefly the results of the survey and its broader implications
      on the health needs of the local population. METHODS: A questionnaire was used to
      obtain basic information regarding the ethnicity/area of origin, number of
      household members and their breakdown according to gender, age and marital
      status. The medical students of different batches were involved in the data
      collection process, as part of their Survey Methodology course of Community
      Health Sciences (CHS) in first year. RESULTS: Data was obtained from 2,033
      houses, having a total population of 16,118 persons. Fifty three per cent of the
      population was under fifteen years, 42% were between 15-49 and 5% were over 50
      years of age. The overall percentage of males was 52% and females 48%.
      Approximately 79 percent people were Pushto speaking. CONCLUSION: Sikanderabad is
      a typical slum settlement, with an emigrant population being mostly of Pathan and
      Afghan refugees. The fertility rate in Sikanderabad is much higher than that of
      Karachi. This highlights the need for education and availability of family
      planning facilities. At the same time, due to the fact that there is a major
      portion of the population aged under five years, so facility for treating
      children must be appropriately provided. The Primary Health Care center
      established in Sikanderabad is based on the above information. The emphasis is on
      maternal and childcare, including antenatal and postnatal care; family planning
      and nutritional counseling.

PMID- 15241997
TI  - Awareness of palliative medicine among Pakistani doctors: a survey.
AB  - OBJECTIVE: To establish the awareness of palliative medicine in Pakistani doctors
      through a questionnaire. METHODS: A questionnaire was developed after
      consultation with the professionals working in palliative medicine. It was
      distributed, by hand, to a convenience sample of doctors who worked at various
      teaching hospitals in Pakistan. The distribution and collection of questionnaires
      was carried out within six months. RESULTS: The results suggested that 74%
      doctors felt that cancer was the commonest reason for the palliative care teams
      to be involved. Forty five percent mentioned tht pain control was their prime
      job; 54% said that they had some experience of palliative medicine; 64% wanted to
      be involved in palliative medicine; 60% thought that they broke bad news properly
      to the patients; 59% were satisfied with their own performance while dealing with
      an incurable patient (57% said that they had heard about a hospice). There was a
      wide range of drugs for the cancer pain. CONCLUSION: Amongst Pakistani doctors,
      there is a lack of training in palliative medicine. A significant number of
      doctors are interested and they are willing to have more training in pain
      control, breaking bad news, communication skills and terminal care.

PMID- 15241998
TI  - Role of methylene blue infusion in per-operative localization of parathyroid
      glands.

PMID- 15241999
TI  - Prevalence of hepatitis C virus in lymphoproliferative disorders.
AB  - OBJECTIVE: To study the prevalence of hepatitis C virus in lymphoproliferative
      disorders. METHODS: A case control prospective study was performed on 143
      patients with lymphoproliferative disorders and 29 patients with non
      hematological malignancies were taken as controls. All the patients in both
      groups were analyzed for various risk factors for infection with hepatitis C
      virus and were tested for the presence of hepatitis C virus antibody (anti HCV),
      cryoglobulins and rheumatoid factor antibody. Hepatitis C viremia was documented
      by detection of HCV RNA by polymerase chain reaction. RESULTS: There was no
      significant difference for risk factors for hepatitis C virus infection in both
      the groups except for the increase in number of surgical procedures being carried
      out in the control group. There was no significant difference in the presence of
      rheumatoid factor antibody in both the groups and cryoglobulins were not positive
      in any individual. Five percent patients with lymphoproliferative disorders and
      3.4% with non-hematological malignancies were positive for anti HCV. HCV RNA was
      detected in 29.2% cases and 31.0% in controls. CONCLUSION: There was no
      association between hepatitis C virus infection and lymphoproliferative disorder
      in our population. However, further studies are required from this region to
      establish any causal relationship between hepatitis C virus infection and
      lymphoproliferative disorder.

PMID- 15242000
TI  - Chemical and biological warfare preparing to meet the threat.

PMID- 15242001
TI  - Severe hypercalcemia in tuberculosis.

PMID- 15242002
TI  - Anti-Rh17 (anti-Hr0): a rare diagnostic and management problem.

PMID- 15242003
TI  - A novel scintigraphic approach for the detection and evaluation of
      bronchopulmonary aspiration.

PMID- 15242004
TI  - Extradural extramedullary hematopoiesis: a rare MRI diagnosis with atypical
      features.

PMID- 15242005
TI  - Calcified posterior part of cricoid cartillage presenting as foreign body
      complicated with retropharyngeal cellulitis.

PMID- 15242006
TI  - Protocols for exercise during pregnancy.

PMID- 15242007
TI  - The Hippocratic Oath: has it ceased to be relevant?

PMID- 15242008
TI  - Variation in esophageal length.

PMID- 15242009
TI  - Recent progress of vitamin B6 biosynthesis.
AB  - This review is the current summary of vitamin B6 (B6) biosynthesis in Escherichia
      coli and other microorganisms. The de novo biosynthesis of B6 has been studied
      extensively for last three decades. However, the de novo biosynthesis of B6 still
      remains unclear in spite of its simple structure. For the first two decades, B6
      biosynthesis had been mainly studied with E. coli using genetic, nutritional, and
      isotopic labeling experiments. According to these studies, some compounds
      including glycolaldehyde were identified as the precursor. During the last
      decade, gene manipulate techniques were rapidly developed, and complete genome
      sequences of some microorganisms became available. Using these new tools,
      valuable information has been provided. The complete DNA sequence of pdx genes
      and other genes, which are possibly involved in B6 biosynthesis, were shown. The
      roles of some genes and precursors were proposed. Besides E. coli, B6
      biosynthesis in other microorganisms has been also studied. In some
      microorganisms, snz/sno was reported to be involved in B6 biosynthesis.
      Intriguingly these genes show no similarity to any of the E. coli pdx genes, and
      are not found in E. coli. Microorganisms having snz/sno gene homologues lack
      homologues to pdxA/pdxJ genes, whereas those with homologues to pdxA/pdxJ lack
      snz/sno gene homologues. Therefore, it is most likely that there are at least two
      kinds of B6 biosynthetic pathways in microorganisms. These studies provided
      important clues of B6 biosynthesis, but the entire picture of the B6 biosynthetic
      pathway remains unclear.

PMID- 15242010
TI  - Low dose-ethanol modulates toxic effect of iron-overloading in the liver.
AB  - The oxidant properties of iron-overload and simultaneous ethanol consumption have
      received much interest, due to evidence reporting from hereditary hemochromatosis
      (HC). The full form of this disease is often associated with chronic alcoholism.
      An additive effect of toxicity of iron and ethanol was assumed. In this study, we
      examined nutritively iron-loaded Wistar rats (n = 59) (TMH-Ferrocene)
      additionally fed with ethanol up to 8% in drinking water for 36 wk. METHODS: By
      reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole
      and retinol in serum and liver homogenates as well as transaminases in the serum.
      Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron
      concentration in the liver was measured with the Bathophenanthrolin-method. Liver
      histology was performed to investigate the iron deposits and the organ damage
      (H.E., Azan and Berlin-blue-stainings). RESULTS: 1. Vitamin C: A linear decrease
      of the concentration of vitamin C in serum and liver was found independent of
      alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed
      elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin
      A: Elevated levels in serum but strongly decreasing levels in liver could be
      measured. 4. HISTOLOGY: All iron-fed animals showed massive deposits of iron in
      the liver. Iron diet caused liver cirrhosis, while an additional administration
      of ethanol could prevent this. 5. Lipid peroxidation increased in animals fed
      ethanol and iron, but was significantly lower in animals only receiving an iron
      diet. CONCLUSION: Evidence indicates that the additional exposition to ethanol in
      iron-loaded animals could modulate the organ damage and oxidative stress. The
      biochemical findings are positively correlated to the histology.

PMID- 15242011
TI  - The multiple vitamin status of Chinese pregnant women with anemia and nonanemia
      in the last trimester.
AB  - Iron-deficiency or anemia in pregnancy is a major public health problem in China.
      This cross-sectional study was carried out to observe the association between
      iron status and multiple vitamin levels of Chinese pregnant women in the third
      trimester. We measured iron, ascorbic acid, retinol, folate and vitamin B12 in
      serum, and riboflavin in urine specimens of 1,163 pregnant women in four sites
      throughout rural and city areas in China. Based on hemoglobin concentrations
      (Hb), the subjects were divided into an anemia group with Hb < 110 g/L or Hb < or
      = 100 g/L as severe anemia group, and nonanemia group with Hb > or = 110 g/L.
      Results showed that 41.58% of the population with serum iron < 700 microg/L and
      51.04% of the population with ferritin < 12 microg/L in the anemia group,
      percentages that were much higher than those in the nonanemia group.
      Relationships between five vitamins and hemoglobin concentrations of all subjects
      were observed. There was a lower level of serum ascorbic acid (291.05 microg/dL)
      in the Hb < or = 100 g/L group than in the Hb > or = 120 g/L group (487.79
      microg/dL) (p < 0.001). Serum levels of vitamin B12 and folate were 445.67 pg/mL
      and 5.94 ng/mL in the Hb < or = 100 g/L group, whose levels were much lower than
      the levels of 502.01 pg/mL (p < 0.012) and 8.07 ng/mL (p < 0.010) respectively in
      the Hb > or = 120 g/L group. Further, cross-sectional analysis showed positive
      correlations between abnormal hematological results and prevalences of vitamin
      deficiencies. The subjects with iron-deficiency anemia had much higher rates of
      vitamin C, folate and vitamin B12 deficiencies than those in the nonanemic
      subjects, and especially in the deficient rates of ascorbic acid and folate in
      the anemia (Hb < 110 g/L) group, which reached 64.04% and 22.70% respectively.
      Moreover, we observed that the decreasing trends of hemoglobin concentrations
      were accompanied by the decreases of serum levels of vitamin A, ascorbic acid,
      folate and vitamin B12. In conclusion, multiple vitamin deficiencies, especially
      ascorbic acid, retinol and folic acid, may be associated with anemia or iron
      deficiency in pregnant women in the last trimester. The study suggested that
      anemic pregnant women in China should be supplemented with iron and multiple
      vitamins simultaneously.

PMID- 15242012
TI  - Resistant starch supplementation influences blood lipid concentrations and
      glucose control in overweight subjects.
AB  - Resistant starch (RS) includes the sum of starch and degradation products of
      starch that resist small intestinal digestion and enter the colon. This study was
      planned to examine the effect of resistant starch on hypolipidemic actions, blood
      glucose, insulin levels and humoral immune responses in healthy overweight
      subjects. Healthy overweight subjects (over 120% of their ideal body weights)
      were fed either 24 g/d of resistant corn starch (RS) or regular corn starch (CS)
      for 21 d with their regular meals. Although this double-blind feeding regiment
      resulted in no significant changes in their weights or other physical parameters
      for the relatively acute period of intakes, there were significant lowering
      effects of serum total cholesterol (p < 0.05) and serum LDL-cholesterol (p <
      0.05) in subjects supplemented RS. Compared with the control starch group, the RS
      supplementation also reduced the mean fasting serum glucose concentrations (p <
      0.05). Resistant starch supplement resulted in the increase in serum
      immunoglobulin G (IgG) concentrations. Serum insulin and complement 3 (C3) were
      unaffected. Tested resistant starch supplementation was reported to be palatable
      with minimal bowel discomfort. These results suggest that RS supplementation
      improves the blood lipid profile and controls the blood glucose levels in healthy
      overweight subjects without bowel discomfort. Therefore, RS has a potential to be
      used as one of the promising food ingredients for reducing risk factors involved
      in the development of atherosclerosis and type 2 diabetes in overweight
      individuals. However, in order to prove RS as a novel therapeutic agent of
      cardiovascular diseases and diabetes, controlled trials with larger sample sizes
      and longer duration are warranted.

PMID- 15242014
TI  - Effects of a high-monounsaturated fat diet on glucose and lipid metabolisms in
      normal and diabetic mice.
AB  - The beneficial effects of high-monounsaturated fat (high-MUFA) diets on diabetic
      patients have been reported, whereas studies concerning the effects on animals
      have been few. Although experiments on animals should be useful in elucidating
      underlying mechanisms, it is not clear even whether there are benefits of a high
      MUFA diet in animals. This study examined the short-term effects of a high-MUFA
      diet on normal and genetically diabetic mice. The high-MUFA diet supplied 38% of
      the total calories as fat (26% from MUFA), while a regular diet was 13% fat (3%
      from MUFA). Normal C5 7BL/6J and diabetic C57BL/KsJ-db/db mice were fed either
      the regular or the high-MUFA diet for 1 wk. Serum glucose and lipid levels were
      then measured. In normal mice, hepatic triglyceride production was also compared
      between the two dietary groups using the Triton WR1339 method. An oral glucose
      tolerance test was conducted on the diabetic mice. After 1 wk of feeding to
      normal mice, the high-MUFA diet was seen to lower serum triglyceride levels and
      reduce hepatic triglyceride production in comparison with the regular diet; it is
      suggested that the lowering of triglyceride consists of mechanisms including
      reduced hepatic triglyceride production. When diabetic mice were fed the high
      MUFA diet with a controlled caloric intake, the serum glucose levels lowered
      without an accompanying deterioration in lipid metabolism and the impaired
      glucose tolerance was ameliorated. This study demonstrates that a high-MUFA diet
      can lower serum triglyceride levels in normal mice and improve disorders of
      glucose metabolism in diabetic mice.

PMID- 15242013
TI  - Estrogenic effects of Sedum sarmentosum Bunge in ovariectomized rats.
AB  - The aim of this study was to evaluate the effects of Sedum sarmentosun Bunge (SS)
      on the lipid on serum and the collagen content of the connective tissues in
      ovariectomized estrogen-deficient rats. Three groups were surgically
      ovariectomized. The fourth group was sham operated. From day 2 until day 37 after
      the ovariectomy, Sprague-Dawley female rats were randomly assigned to the
      following groups: sham-operated rats (sham), ovariectomized control rats (OVX
      control), ovariectomized rats supplemented with an ethyl ether fraction of SS at
      10 mg/kg bw/d (OVX-EE), ovariectomized rats supplemented an ethyl acetate
      fraction of SS at 10 mg/kg bw/d (OVX-EA). The SS fractions were orally
      administrated at 1 mL per day. The estrogenic effects of the ethyl ether and
      ethyl acetate fractions of SS, were investigated using one in vitro assay and two
      in vivo assays. The treatment of the partition of the ethyl ether and ethyl
      acetate layers of SS increased the transcriptional activity 0.7-fold and 0.5-fold
      compared to those that were given 17beta-estradiol treatment, respectively. The
      OVX rats were significantly heavier than the sham-operated rats at all times, but
      supplementation with the SS extracts tended to result in less weight gain than
      OVX-control. The serum triglyceride levels were significantly decreased after
      supplementation with the SS portion EE and EA layers. Supplementation with the SS
      extracts prevented a decrease in the collagen level in bone and cartilage
      tissues. This result indicates that the SS affects the collagen synthesis in
      ovariectomized rats. These results are consistent with the conclusions based on
      the estrogenic activities of SS. Therefore, it may be used to possibly improve
      the quality of life in menopausal women.

PMID- 15242015
TI  - Promotion of bone formation by fermented soybean (Natto) intake in premenopausal
      women.
AB  - A therapeutic agent of vitamin K2 is approved for the treatment of osteoporosis
      in Japan. However, little is known about the efficacy of dietary intake of
      vitamin K2 for bone health. We compared the effects of various levels of
      fermented soybeans (Natto) intake, which contains plenty of vitamin K2, on bone
      stiffness and bone turnover markers in healthy premenopausal women. Seventy-three
      healthy premenopausal women were randomly divided into four groups matched for
      age and parity categories. Natto was supplied as follows: Group 1 (no intake),
      Group 2 (once per month), Group 3 (once per week) and Group 4 (three times per
      week). Subjects took Natto at a lunch for 1 y, and the stiffness index by
      quantitative ultrasound and bone turnover markers were assessed at baseline, 6 mo
      and 1 y. There was no statistical difference in the stiffness index during the 1
      y observation. However, bone specific alkaline phosphatase (BAP) in Group 4 was
      higher than that in Group 3 at 1 y and undercarboxylated osteocalcin (Glu) in
      Group 4 was significantly lower than those in Groups 1, 2 and 3 at 6 mo. Logistic
      regression analysis showed that the risk of reduction of bone formation markers
      declined to 0.07 in Group 4 based on that in Group 1. In premenopausal women who
      had to keep the stiffness index as high as possible before menopause, Natto
      intake may have contributed to the promotion of bone formation.

PMID- 15242016
TI  - Recommended methods of fatty acid methylester preparation for conjugated dienes
      and trienes in food and biological samples.
AB  - In this study, we compared three acid-catalyzed methods and three base-catalyzed
      methods for the methylester preparation of conjugated dienoic fatty acids and
      conjugated trienoic fatty acids in food and biological samples. Among the six
      methods examined, the sodium methoxide/methanol (NaOCH3/MeOH) method and the
      tetramethylguanidine/ methanol (TMG/MeOH) method of methylester preparation from
      tung oil were most efficient in preventing the artificial isomerization of alpha
      eleostearic acid (alpha-ESA; 9c,11t,13t-18:3) to beta-eleostearic acid (beta-ESA:
      9t,11t,13t-18:3) and for avoiding the artificial generation of unknown
      byproducts. Hydrochloric acid/methanol (HCl/MeOH), sulfuric acid/methanol
      (H2SO4/MeOH) and AOCS (boron trifluoride/methanol (BF3/MeOH)) methods of
      methylester preparation from tung oil resulted in the breakdown of alpha-ESA due
      to their long reaction periods and high reaction temperatures. In addition, these
      three methods did not prevent the generation of beta-ESA. For the methylester
      preparation of tung oil free fatty acids, the BF3/MeOH method (30 min at room
      temperature) did not lead to artificial beta-ESA formation or byproducts, while
      the trimethylsilyldiazomethane (TMSN2CH3) method did form artifacts. For the
      methylation of conjugated linoleic acid (CLA, free fatty acid), the BF3/ MeOH and
      TMSN2CH3 methods completely suppressed artificial isomerization of c,t-CLA and
      t,c-CLA to t,t-CLA. The results indicated that the BF3/MeOH method for free fatty
      acids is the best method for the methylester preparation of both conjugated
      dienoic and trienoic fatty acids with respect to preventing artificial
      isomerization and the formation of byproducts. The BF3/MeOH method was applicable
      to both food and biological samples.

PMID- 15242017
TI  - Phycocyanin enhances secretary IgA antibody response and suppresses allergic IgE
      antibody response in mice immunized with antigen-entrapped biodegradable
      microparticles.
AB  - In the present study, we have investigated the effects of phycocyanin, a
      biliprotein of Spirulina platensis, on mucosal and systemic immune responses and
      allergic inflammation in C3H/HeN and BALB/cA mice. To induce the antigen-specific
      antibodies in the peripheral lymphoid tissues such as Peyer's patches and
      mesenteric lymph nodes, biodegradable ovalbumin-entrapped poly (DL-lactide-co
      glycolide) particles were used as an antigen. Two weeks after the onset of
      phycocyanin ingestion, mice were immunized with an aqueous ovalbumin (OVA)
      solution. Starting at one week after the primary immunization, the mice were
      subjected to oral immunization with the biodegradable OVA microparticles twice a
      week. IgA, IgE and IgG1 antibodies were determined by ELISA. The OVA
      microparticles of 4-microm diameter successfully induced antigen-specific
      antibodies. In the mice that received phycocyanin treatment for 6 wk, a marked
      increase in the antigen-specific, as well as the total, IgA antibody level was
      observed in the Peyer's patches, mesenteric lymph nodes and intestinal mucosa as
      well as in the spleen cells. Both antigen-specific IgG1 and IgE antibody levels
      in the serum were suppressed by ingestion of phycocyanin for 8 wk. However,
      inflammation of the small intestine, monitored as vascular permeability by the
      Evans blue-leaking method was reduced by phycocyanin at 6 wk, which preceded the
      suppression of antigen-specific IgG1 and IgE antibody production by 2 wk. These
      results suggest that phycocyanin enhances biological defense activity against
      infectious diseases through sustaining functions of the mucosal immune system and
      reduces allergic inflammation by the suppression of antigen-specific IgE
      antibody.

PMID- 15242018
TI  - Effect of branched-chain fatty acids on fatty acid biosynthesis of human breast
      cancer cells.
AB  - This paper describes the antitumoral activity of branched-chain fatty acid (BCFA)
      in human breast cancer cells with an emphasis on its effect on fatty acid
      biosynthesis. First, the relationship between chain-length and antitumoral
      activity was studied. The highest activity was observed with iso-16:0, and the
      activity decreased with increase or decrease of the chain-lengths from C16:0.
      Anteiso-BCFA, as well as iso-series, was cytotoxic to the breast cancer cells.
      Cytotoxicity of BCFA was comparable to that of conjugated linoleic acid known as
      antitumoral fatty acid. Incubation of breast cancer cells with BCFA (13
      methyltetradecanoic acid) significantly reduced the [14C] acetate incorporation
      into free fatty acid and fatty acid esters, showing the inhibition of fatty acid
      biosynthesis by BCFA. Examination of substrate level effect found that BCFA
      slightly inhibited fatty acid synthetase and acetyl-CoA carboxylase, and
      significantly the glucose-6-phosphate dehydrogenase which was the main NADPH
      generating system in breast cancer cells. The present study thus suggests that
      BCFA synthetically lowers the fatty acid biosynthesis by reducing the precursors,
      in addition to its direct inhibitory effect on fatty acid synthetase.

PMID- 15242019
TI  - Expressional changes of neuropeptide Y and cholecystokinin in the arcuate and
      paraventricular nuclei after capsaicin administration.
AB  - Despite its toxicity, a great deal of attention has been paid to the anorexic
      effect of capsaicin in the treatment of obesity-related
      neurotransmitters/neuromodulators. To determine if capsaicin has any effects on
      the orexigenic or anorexigenic peptides, the neuropeptide Y (NPY)- and
      cholecystokinin (CCK)-immunoreactivities were demonstrated in the rat
      hypothalamus by immunohistochemistry after capsaicin administration. There was a
      significantly lower concentration of NPY immunopositive cells in the arcuate and
      paraventricular nuclei of the capsaicin treated rats. In contrast, the CCK
      expressions level was higher in the paraventricular nucleus of the capsaicin
      treated rats than in the control rats. These results suggest that capsaicin
      influence neuropeptides such as orexigenic NPY and anorexigenic CCK related to
      control food intake.

PMID- 15242020
TI  - Short-term ascorbic acid deficiency does not impair antioxidant status in lens of
      guinea pigs.
AB  - We examined whether short-term ascorbic acid deficiency impairs antioxidant
      status in the lens of guinea pigs. Male guinea pigs aged 4 wk were given a
      scorbutic diet (20 g/animal per day) with and without ascorbic acid (400
      mg/animal per day) in drinking water for 3 wk. The ascorbic acid-deficient group
      showed no lens opacity. The ascorbic acid-deficient group had 14% of serum
      ascorbic acid concentration, 6% of aqueous humor ascorbic acid concentration, and
      18% of lens ascorbic acid content in the ascorbic acid-adequate group. There were
      no differences in the contents of lens reduced glutathione and thiobarbituric
      acid reactive substances, an index of lipid peroxidation, between the ascorbic
      acid-deficient and adequate groups, while the deficient group had higher lens
      vitamin E content than the adequate group. The ascorbic acid-deficient group had
      higher serum vitamin E concentration than the ascorbic acid adequate group, while
      there were no differences in the concentrations of serum reduced glutathione and
      tiobarbituric acid reactive substances between the deficient and adequate groups.
      These results indicate that short-term ascorbic acid deficiency does not impair
      antioxidant status in the lens of guinea pigs despite induction of severe
      ascorbic acid depletion in the tissue, which may result in no cataract formation.

PMID- 15242021
TI  - Sociodemographic and clinical determinants of quality of life in urban population
      of Poland.
AB  - The aim of the study was to assess quality of life (QL) of residents of Polish
      urban area and analyze the influence of selected sociodemographic and clinical
      variables on their QL. The study revealed a very high level of reported problems,
      especially regarding pain and anxiety. The mean subjective assessment of health
      state was poor in comparison with results obtained in other (usually western)
      countries. Presence of major risk factors of cardiovascular diseases had an
      important impact on QL. Elevated blood pressure and unsatisfactory level of
      physical activity were the strongest factors deteriorating QL in the studied
      population. There is a need for implementing effective interventions in the
      society, especially in the area of prevention and management of hypertension and
      sedentary lifestyle.

PMID- 15242022
TI  - The role of information for improvement of patients' treatment in Bulgaria.
AB  - PURPOSE: This issue is an attempt to assess patients' role as regards their
      compliance, respectively their non-compliance. The authors try to elucidate the
      factors concerning the patient-physician interrelation and patient-pharmacist
      interrelation that influence the non-compliance in order to increase the
      compliance rate. METHODS: Standard individual questionnaires and interviews were
      developed and applied to study an attitude to compliance and non-compliance among
      different categories of patients, suffering from chronic diseases. RESULTS: The
      obtained results show that the main reasons, influencing the patients' non
      adherence to physicians' advise are: the high price of the drugs, the
      overburdened daily regimen, negligence, distrust towards the treatment and
      others. The insufficient information in the patient's leaflet together with the
      inappropriate drug form appears to be the main factors that cause non-compliance.
      This happens especially in the cases, when the patients are treated with more
      than one drug in different drug forms and particularly it concerns elderly
      people. Even though the compliance among the patients investigated was
      comparatively high (50% to 92%), possibility for improvement still exists if the
      treatment that have to be initiated could be individualised. Thus the level of
      compliance will be improved and increased. DISCUSSION: The results from the data
      analysis show a great variation in the level of compliance among the chronic
      patients in Bulgaria. It ranges from 50 to 92%, depending on the type of the
      chronic disease and on the age of the patients. This fact shows the necessity for
      improvement of the different factors that has to begin as soon as possible.

PMID- 15242023
TI  - Trends in the incidence of childhood-onset type 1 diabetes in Slovakia 1985 -
      2000.
AB  - The aim of this work was to study and monitor the patterns in incidence of
      childhood type 1 diabetes in Slovakia. The incidence of type 1 diabetes per
      100,000/year from 1985 to 2000 was determined in children 0 - 14 years old. A
      total of 1,818 cases were diagnosed during this time. Poisson regression models
      were used to study incidence trends. The overall incidence of type 1 diabetes
      varied from 5.62/100,000 per year in year 1986 to 14.46/100,000 in year 1998.
      This represents a 2.57-fold increase. The incidence increased with age and was
      the highest among children 10 - 14 years of age. The incidence of type 1 diabetes
      in Slovakia is increasing very dramatically, especially in age group 0 - 4 years.

PMID- 15242024
TI  - Does hyperglycaemia cause symptoms in elderly people?
AB  - The aim of the present study was to describe the associations between glucose
      tolerance and symptoms in an unselected non-institutionalised elderly population
      aged 73 years or over (n = 259, of whom 93 were men). Diabetes was assessed on
      the basis of self-reports and 2-h oral glucose tolerance tests (1985 WHO
      criteria). Symptoms were measured with a modified diabetes symptom checklist (DSC
      Type 2). The previously diagnosed diabetic patients reported to have more
      symptoms in all the six dimensions of the symptom checklist than the other study
      groups. According to the responses to twenty out of 34 items, more of the
      previously diagnosed diabetic women had symptoms than the other female study
      groups; the corresponding figure for the previously diagnosed diabetic men being
      16/34. The following hyperglycaemic symptoms: "dry mouth", "increasing fatigue in
      the course of the day", "numbness in the hands", were either weakly or
      significantly associated with undiagnosed diabetes. Men with IGT reported to have
      "dry mouth" and "tingling or pricking in the legs or feet" more often than men
      with NGT. Symptoms of "moodiness" increased along with the deterioration of
      glucose tolerance, and it seems that depression is associated with type 2
      diabetes in elderly people, too. Although the study covered a wide range of
      symptoms, it did not clearly reveal such symptoms that could be used as potential
      indicators of undiagnosed diabetes or especially IGT among elderly patients.

PMID- 15242025
TI  - Milk and milk products consumption in relationship to serum lipid levels: a
      community-based study of middle-aged and older population in Japan.
AB  - The authors examined the association of milk and milk products consumption (MMPC)
      with serum lipid profiles including total cholesterol (TC), triacylglycerols
      (TG), HDL cholesterol (HDLC), LDL cholesterol (LDLC), and TC/HDLC ratio in a
      community-based sample. The study population comprised 461 men and 834 women aged
      40-79 years who, in 2001, participated in an annual healthy examination and a
      lifestyle related survey Consumption frequency of 17 foods, including milk and
      milk products, was determined by a self-administered questionnaire. The
      participants were asked by "Do you drink cow's milk or eat milk products such as
      yoghurt and cheese everyday?", and two groups ("Yes" and "No") of MMPC were
      classified. Multiple linear regression analyses were conducted to examine the
      relationships between MMPC and 5 serum lipid profile levels adjusted for sex,
      age, body mass index (BMI), alcohol consumption, smoking, physical activity, and
      fat intake. Univariate and multivariate analyses indicated inverse associations
      of MMPC with TC, HDLC, and LDLC, and that the "Yes" group had higher adjusted
      means of serum TC by 7.133 mg/100 ml (p < 0.001), HDLC by 1.844 mg/100 ml (p <
      0.05), LDLC by 5.459 mg/100 ml (p < 0.001). We suggested that MMPC has an
      association with serum lipid and lipoprotein levels and that MMPC may have an
      unfavorable effect on hypercholesterolaemia in the Japanese population.

PMID- 15242026
TI  - The background of beta-oxidation disorders in humans. I. Theory.
AB  - Disorders in energetical processes are described from the point of view of energy
      production and the possibility of substitution of substrates for ATP synthesis.
      The effects of other diet components such as microelements (Cr3+ ions) and non
      digestible oligofructans (inulin and oligofructose) as stimulatory factors on the
      activity of beta-oxidation and cholesterol and triacylglyceroles levels lowering
      are reported.

PMID- 15242027
TI  - The background of beta-oxidation disorders in humans. II. Laboratoy studies and
      clinical data.
AB  - Laboratory method for studies of clinical disorders of beta-oxidation is
      described. The effects of other diet components such as microelements (Cr3+ ions)
      and non-digestible oligofructans (inulin and oligofructose) as stimulatory
      factors on the activity of beta-oxidation and cholesterol and triacylglyceroles
      levels lowering are reported.

PMID- 15242028
TI  - Budapest Student Health Behavior Survey--Budapest, Hungary, 1999. Findings on
      unintentional and intentional injuries, alcohol use, and sexual activity.
AB  - OBJECTIVE: In Hungary, a large proportion of adult morbidity and mortality can be
      attributed to health risk behaviors that begin in early adolescence. To date,
      studies examining health risk behaviors among youth have rarely been undertaken
      in Hungary. In order to expand current research in this area, the Hungarian
      Metropolitan Institute of State Public Health and Public Health Officer Service
      and the Office on Smoking and Health at the U.S. Centers for Disease Control and
      Prevention developed and implemented the Budapest Student Health Behavior Survey.
      The objective of this study was to examine health behavior risk factors among
      secondary school students in Budapest in 1999. METHODS: The 1999 Budapest Student
      Health Behavior Survey is cross-sectional school-based survey A 2-stage cluster
      sampling design was used to produce a representative sample of secondary students
      in grades 9-12 in Budapest. Information was collected on unintentional and
      intentional injuries, alcohol use, and sexual activity. FINDINGS: During the 30
      days preceding the survey, 28.7% of students had rarely or never worn a seatbelt
      and 68.1% drunk alcohol. During the 12 months preceding the survey, 14.5% had
      been threatened or injured with a weapon, 12.9% experienced dating violence, and
      13.5% seriously considered suicide. Of the 44.7% of students who had had sexual
      intercourse, 29.5% had > or = 4 sex partners. Of sexually active students, 50.4%
      had not used a condom at last sexual intercourse. CONCLUSION: Many secondary
      school students in Budapest practice behaviors that place them at risk for
      serious health problems both in the short and long-term. Programs and policies
      that adequately address such behaviors among secondary school students are needed
      to reduce subsequent morbidity and mortality.

PMID- 15242029
TI  - Importance of serum bile acids determination in adolescents with juvenile
      hyperbilirubinaemia.
AB  - The aim of the study was to identify moderate liver impairment in a group of
      hyperbilirubinaemic adolescents. Using gas chromatography we assessed both total
      bile acid and primary bile acid levels in 50 adolescents with juvenile
      hyperbilirubinaemia. At the same time we performed hepatologic examinations and
      subsequent follow-up assessment of these patients for a period of at least 2
      years. As a control group we examined 30 adolescents without any impairment of
      both the liver and gastrointestinal tract, and 18 patients with low grade
      (moderately) active chronic hepatitis. In both groups we assessed total and
      primary bile acids levels as well as conventional liver tests (bilirubin, ALT,
      AST). On the basis of the clinical course and laboratory findings we divided our
      patients with juvenile hyperbilirubinaemia into two groups: a group of
      individuals with Gilbert's syndrome (30 patients) and a group of individuals with
      probable moderate liver impairment (20 patients). The latter group consisted of
      the adolescents who exhibited bilirubinaemia over 90 micromol/l and/or exhibited
      hepatomegaly or splenomegaly proved by the ultrasound examination and/or
      exhibited intermittent elevation of the liver aminotransferases serum levels. In
      the group of individuals with moderate liver impairment serum total bile acid
      levels were significantly elevated in 26% of patients, and the serum cholic acid
      level was significantly elevated in 25% of patients. These two parameters
      mutually correlated at a high level of significance. Juvenile hyperbilirubinaemia
      is one of the common conditions of adolescent age. Its etiology is diverse; it
      includes both benign conditions like Gilbert's syndrome and post-hepatitic and
      toxic conditions that require a long-term regimen and follow-up examinations. The
      number of people suffering from juvenile hyperbilirubinaemia has been growing in
      the population. Currently 4-6% of the adolescent population suffers from this
      disease. This growing number is probably caused by external factors of our
      environment (infection, toxic effects). The determination of mild liver disease
      in hyperbilirubinaemic patients and the provision of an adequate regimen of
      exercise and adequate nutritional measures is of great importance for the health
      of the adolescent population.

PMID- 15242030
TI  - Breastfeeding promotion and protection in the Czech Republic.
AB  - The purpose of the article is to present the National Breastfeeding Promotion
      Programme in the Czech Republic in the course of the last decade. It summarizes
      the main strategies, education and training activities of the National
      Breastfeeding Committee, its collaboration with the Government, Parliament, IBFAN
      and UNICEF. The article reviews the relevant studies on infant feeding which
      illustrate the increase of the prevalence of breastfeeding in the course of the
      1990's and reflect the effect of the programme. Recent negotiations with the
      Ministry of Health have outlined the implementation of the WHO global strategy
      for infant and young child feeding in the Czech Republic.

PMID- 15242031
TI  - Taxation and life expectancy in Western Europe.
AB  - With the exception of Denmark, life expectancy in Western Europe has shown a
      significant increase over the last decades. During that period of time overall
      taxation has increased in most of the countries, especially in Denmark. We,
      therefore, examined whether taxation could influence life expectancy in Western
      Europe. We used information on the sum of income tax and employees' social
      contribution in percentage of gross wage earnings from the OECD database and data
      on disability adjusted life expectancy at birth from the World Health
      Organization database. We arbitrarily only included countries with populations in
      excess of 4 millions and thereby excluded smaller countries where tax exemption
      is part of the national monetary policy. We found that disability adjusted life
      expectancy at birth was inversely correlated to the total tax burden in Western
      Europe. We speculate whether a threshold exists where high taxes exert a negative
      influence on life expectancy despite increased welfare spending. The study
      suggests that tax burden should be considered among the multiple factors
      influencing life expectancy.

PMID- 15242033
TI  - [Bispectral index monitoring in fast track pediatric cardiac surgery].
AB  - BACKGROUND: We evaluated the changes in the bispectral index (BIS) as a potential
      indicator of level of consciousness in infants and children undergoing fast track
      cardiac surgery. METHODS: Twenty-one children undergoing fast track cardiac
      surgery were recruited into this study. Anesthesia was maintained with inhaled
      sevoflurane and intravenous fentanyl 10 microg x kg(-1). Cardiopulmonary bypass
      (CPB) with mild hypothermia and an immediate tracheal extubation protocol were
      used. BIS was recorded throughout the operation. RESULTS: In average, BIS was
      kept almost under 70 with 0.5-3.0% of sevoflurane. During rewarming from mild
      hypothermia, BIS increased temporarily over 70 in about a half of children. We,
      therefore, treated them by increasing sevoflurane concentration. Nineteen
      children were extubated in the operating room, and two patients were extubated in
      ICU within three hours after surgery. CONCLUSIONS: BIS was kept within the level
      of adequate sedation during surgery. However, since the increase in BIS during
      the rewarming phase could reflect light anesthesia, caution should be taken
      around this phase.

PMID- 15242032
TI  - [Effect of respiratory care on pulmonary function in patients after
      cardiopulmonary bypass].
AB  - BACKGROUND: Respiratory failure after cardiopulmonary bypass (CPB) remains one of
      the major complications after cardiac surgery. This study was designed to
      evaluate effects of respiratory care after CPB on pulmonary function. METHODS:
      Eighteen patients scheduled for cardiac surgery were investigated. Preoperative
      respiratory functions (%VC, FEV1.0%, V25/Ht, FRC-CC, deltaN2) were measured in
      all the patients. Both induction and maintenance of anesthesia were performed
      using propofol, midazolam, fentanyl, and vecuronium bromide. All the patients
      were ventilated using volume controlled ventilation by setting FIO2 at 0.5, the
      respiratory frequency at 15 x min(-1), the tidal volume at 6-10 ml x kg(-1)
      adjusted to maintain PaCO2 between 30 to 40 mmHg, and the peak airway pressures
      below 40 cmH2O, PEEP of 0 cmH2O. From 1 hour after the operation, the patients
      were randomly divided into 2 groups: group A, ventilated artificially with PEEP
      of 5 cmH2O and group B, ventilated with PEEP adjusted to the patient's lower
      inflection point (LIP) obtained by the pressure-volume curve. PaO2, Qs/Qt and FRC
      were measured after induction of anesthesia, just after surgery, 1 hour after
      surgery and 1 hour after artificial ventilation with PEEP. The values of the LIP
      were obtained from the P-V curves with the constant-flow methods before and after
      surgery. RESULTS: PaO2 and FRC decreased and Qs/Qt increased significantly after
      the surgery in all the patients. One hour after artificial ventilation with PEEP,
      PaO2 increased and Qs/Qt decreased significantly compared with the values after
      operation. However, there was no significant difference in the magnitude of these
      changes among the different groups. The changes in PaO2 and Qs/Qt were not
      correlated with the changes in FRC and preoperative respiratory functions. The
      LIP tended to increase after surgery in 2 groups. CONCLUSIONS: Although pulmonary
      function deteriorated after CPB. PEEP could improve oxygenation in all the
      patients. There were no significant differences in the degree of these
      improvements between patients receiving PEEP of 5 cmH2O and patients with PEEP
      adjusted to their LIP. There was no significant relationship between preoperative
      pulmonary function and changes in oxygenation after CPB.

PMID- 15242034
TI  - [A comparison of combined spinal-epidural anesthesia with epidural anesthesia for
      postoperative pain relief after transurethral resection of the prostate].
AB  - BACKGROUND: We compared combined spinal-epidural anesthesia (S group) and
      epidural anesthesia (E group) in terms of pain control after transurethral
      resection of the prostate (TUR-P). METHODS: All 32 patients received 0.2%
      ropivacaine at a rate of 2 ml x hr(-1) by a portable disposable pump
      postoperatively. RESULTS: S group was superior to E group in urethral pain
      control within three hours after operation. E group was superior to S group in
      decrease of back pain over six hours after operation. Fifteen patients (47%)
      suffered from irritability or low back pain and needed rescue analgesics.
      CONCLUSIONS: Our result indicates that 0.2% ropivacaine at a rate of 2 ml x hr(
      1) is not satisfactory to relieve the postoperative pain. Long acting local
      anesthetics for spinal anesthesia are not suitable for TUR-P. Supplemental
      administration of opioid to epidural space or higher rate of continuous epidural
      infusor after operation might be better analgesic choice for TUR-P.

PMID- 15242035
TI  - [Changes in serum Na+ and blood hemoglobin levels during three types of
      transurethral procedures for the treatment of benign prostatic hypertrophy].
AB  - BACKGROUND: Transurethral holmium YAG laser resection of the prostate (HoLR-P)
      and transurethral electrovaporization of the prostate (TUV-P) have recently
      received increasing attention as an effective minimally invasive approach for the
      treatment of prostatic hypertrophy. However, less information is available
      regarding the intraoperative changes in the serum Na+ and blood hemoglobin levels
      during either HoLR-P or TUV-P. METHODS: Intraoperative changes in serum Na+ and
      blood hemoglobin levels were investigated in 17 patients undergoing transurethral
      resection of the prostate (TUR-P, n = 7), HoLR-P (n = 7) or TUV-P (n = 3). The 3%
      D-sorbitol solution was used as the irrigating fluid in all the patients.
      RESULTS: In three patients, severe hyponatremia (118-123 mEq x l(-1)) developed
      abruptly (< or = 15 min) at various time points during TUR-P with (n = 1) or
      without (n = 2) cystostomy. However, no clinical symptoms were observed after
      development of the hyponatremia in those awake patients. No large (> 10 mEq x l(
      1)) decreases in the Na+ level were observed in any of the patients undergoing
      HoLR-P or TUV-P. In patients undergoing TUR-P and HoLR-P, percent changes in
      serum Na+ level significantly correlated with those in blood hemoglobin level,
      but not with the resection time; the slopes were significantly larger than unity.
      CONCLUSIONS: The TUR syndrome is less likely to occur during HoLR-P or TUV-P.
      During TUR-P, the onset of severe hyponatremia appears to be unpredictable, and
      may not necessarily be accompanied by clinical symptoms. Frequent measurements of
      the serum Na+ level appear essential for early detection of severe hyponatremia.

PMID- 15242036
TI  - [Pulmonary emboli in sclerotherapy for peripheral vascular malformations under
      general anesthesia; a report of two cases].
AB  - Sclerotherapy with absolute ethanol and/or polidocanol is a well-established
      therapeutic modality for the treatment of peripheral vascular malformations,
      although systemic complications such as hemoglobinuria and pulmonary embolism
      could occur. We report two cases of pulmonary embolism associated with
      sclerotherapy for peripheral vascular malformations. Two patients, a 17-year-old
      man and a 17-year-old woman, undergoing absolute ethanol sclerotherapy for
      vascular malformations of the leg developed pulmonary embolism after injection of
      ethanol. Pulmonary embolism, suspected by the clinical symptoms such as hypoxia
      and hypocapnia, was confirmed by the pulmonary scintigraphy showing minimal
      pulmonary defects. Hemoglobinuria was also observed with injection of ethanol.
      Patients recovered rapidly with heparin and urokinase therapy. The review of
      perioperative complications with sclerotherapy for peripheral vascular
      malformations in our institution for past four years revealed that complications
      were observed in 18 out of 88 patients (20.5%), and in 32 out of 183 cases
      (17.5%). Major complications were hemoglobinuria, pulmonary embolism, shivering
      and delayed emergence from general anesthesia. We conclude that sclerotherapy for
      vascular malformations under general anesthesia is a risky procedure and this
      must be carefully managed with keen monitoring of Spo2 and Etco2.

PMID- 15242037
TI  - [The effect of nitrous oxide on the central nervous system evaluated by the
      bispectral index under various levels of propofol anesthesia].
AB  - BACKGROUND: The effect of nitrous oxide either as a sole agent or with volatile
      anesthetic agents on the central nervous system has been well studied. However,
      it has not been clarified during various levels of propofol anesthesia. We
      therefore evaluated the effect of nitrous oxide on the central nervous system
      using bispectral index (BIS) and suppression ratio (SR) under various levels of
      propofol anesthesia. METHODS: Twelve patients were enrolled for the study. After
      the administration of subarachnoid block, propofol was infused using a stepped
      down series (effect site concentration of 5, 4, 3 microg x ml(-1)) for 20
      minutes. After obtaining BIS and SR at each concentration, nitrous oxide was
      added. RESULTS: When 67% of nitrous oxide was added to the estimated effect site
      propofol concentration of 5 microg x ml(-1), BIS decreased and SR increased
      indicating that the nitrous oxide had a depressant effect on the central nervous
      system. On the other hand, nitrous oxide combined with 3 or 4 microg x ml(-1) of
      propofol did not cause significant changes in BIS and SR, suggesting that nitrous
      oxide did not have a suppressive effect. CONCLUSIONS: We conclude that nitrous
      oxide has different effects on BIS according to their basal propofol
      concentrations.

PMID- 15242038
TI  - [Effect of airway pressure and Trendelenburg position on the cross-sectional area
      of the internal jugular vein in anesthetized patients].
AB  - BACKGROUND: Several maneuvers such as, Trendelenburg position or breath holding,
      are proposed to increase success rate and decrease complications during internal
      jugular vein cannulation. We investigated the relationship between the cross
      sectional area of the right internal jugular vein (RIJV) and several maneuvers in
      anesthetized patients. METHODS: We studied 18 adult patients (10 males, 8
      females) undergoing RIJV cannulation after anesthetic induction and endotracheal
      intubation. We measured cross-sectional area of the RIJV at the level of the
      cricoid cartilage using ultrasound imaging and standardized by dividing it with
      body weight. Measurements were taken at supine position (S), supine plus 20 cmH2O
      breath hold (SH), 10 degrees Trendelenburg position (T-position) (T), and 10
      degrees T-position plus 20 cmH2O breath hold (TH). We also measured blood volume
      (BV) with pulse dye-densitometry. RESULTS: The standardized cross-sectional areas
      of the RIJV during S, SH, T and TH maneuvers were 1.92 +/- 1.5, 2.82 +/- 1.8,
      2.71 +/- 1.5, 3.51 +/- 1.6 mm2 x kg(-1), respectively. Every maneuver increased
      significantly the cross-sectional area compared to that of supine position (P <
      0.05). The effects of the maneuvers tended to be larger when the BV was smaller.
      CONCLUSIONS: Breath holding at 20 cmH2O and 10 degrees T-position showed almost
      the same dilatation effects on RIJV (164%, 159%). Simultaneous performance of the
      both maneuvers was most effective (222%) in dilating cross-sectional area of RIJV
      in anesthetized patients.

PMID- 15242039
TI  - [Low oxygen saturation during early postoperative period in adult patients
      receiving opioids by intravenous patient-controlled analgesia].
AB  - BACKGROUND: Patient-controlled analgesia (PCA) provides effective postoperative
      analgesia. However, there are few reports concerning the adverse outcome of
      respiratory depression. METHODS: We measured arterial oxygen saturation (SpO2)
      continuously during early postoperative period in 38 adult patients receiving
      opioids by intravenous PCA. We assessed the severity and incidence of
      desaturation, defined as SpO2 below 90% for more than 10 seconds. RESULTS: Nine
      patients showed desaturation and were studied after the surgery of the
      extremities, body surfaces, thorax or abdomen. Two patients showed desaturation
      with combination of surgery of long duration and obesity. Six patients, all of
      whom with liver cirrhosis, underwent thoracic and abdominal procedures, and
      showed desaturation because of respiratory dysfunction and hypoxemia caused by
      the surgery itself. One patient showed respiratory depression due to the opioids.
      CONCLUSIONS: We conclude that careful monitoring with a pulse oximeter and giving
      oxygen are essential to prevent desaturation during early postoperative period.

PMID- 15242040
TI  - [A case of pyogenic osteomyelitis of the cervical spine following stellate
      ganglion block].
AB  - A 56-year-old woman had been treated with stellate ganglion block (SGB) for
      pigmentation degeneration retinopathy over 6 years. She had no history of
      diabetes mellitus or immunodeficiency. She complained of high back pain but was
      afebrile. She was diagnosed as pyogenic osteomyelitis by the MRI findings and
      hematological examination. Antibiotics was administerd for 3 weeks and
      inflammatory signs disappeared. We should bear in mind that pyogenic
      osteomyelitis is very rare but one of the most serious complications with SGB.

PMID- 15242041
TI  - [Living-related liver transplantation in a patient with hepatopulmonary
      syndrome].
AB  - We experienced the perioperative management of the living related liver
      transplantation (LRLT) in a patient with hepatopulmonary syndrome (HPS). HPS is
      seen in 15% of patients of the endstage liver failure, and it accompanies the
      various types of hypoxia. The diagnostic standards of HPS are chronic liver
      disease usually complicated by portal hypertension with or without cirrhosis,
      arterial hypoxemia (PaO2 < 70 mmHg or A-aDO2 gradient > 20 mmHg), and
      intrapulmonary vascular dilation. The present case conformed to the diagnostic
      standard. But this case was of a mild type of HPS, because PaO2 was elevated
      after O2 inhalation and extrapulmonary uptake of 99mTcMAA after lung perfusion
      was lower than 40%. During perioperative period of LRLT, there were no
      complications such as hypoxia, acute rejection, bleeding and infection. Therefore
      HPS would be improved after LRLT. In the management of perioperative period it is
      important to be aware of hypoxia and to evaluate preoperatively the condition of
      the patient properly.

PMID- 15242042
TI  - [Two cases of negative pressure pulmonary edema after induction of anesthesia and
      extubation].
AB  - Two cases of negative pressure pulmonary edema are described. In one case,
      tracheal intubation was not successful and airway obstruction occurred after
      induction of anesthesia. Spontaneous breathing was restored by reversal of
      neuromuscular blocking action, but airway obstruction persisted. Urgent
      tracheostomy was therefore performed. A chest x-ray and clinical features
      indicated pulmonary edema immediately after tracheostomy. Treatment with
      mechanical ventilation and positive end-expiratory pressure improved pulmonary
      edema. In the other case, airway obstruction occurred after extubation. Removal
      of secretion in the oral cavity and assisted ventilation improved airway
      obstruction, but pulmonary edema was found by chest x-ray. Forced diuresis using
      furosemide and oxygen inhalation resulted in the improvement of pulmonary edema.
      Fortunatetly, in both cases, significant complications associated with pulmonary
      edema did not occur. Care should be taken of the risk of pulmonary edema when the
      airway was obstructed after induction of anesthesia or extubation under
      spontaneous breathing.

PMID- 15242043
TI  - [A case of latex allergy induced by indwelt Foley catheter].
AB  - A 7-year-old boy with microtia was scheduled for otoplasty under general
      anesthesia. A Foley catheter was indwelt very gently following tracheal
      intubation but his foreskin showed remarkable edema about 15 minutes later. All
      vital signs were normal. His lungs were ventilated easily and no rash or edema
      was found except for penis. Operation was completed uneventfully as planned. He
      recovered from anesthesia smoothly but foreskin edema still remained. Allergic
      reaction was suspected and scratch test was performed to determine the allergen
      on the next day. Positive reaction to Foley catheter extracts and high serum
      latex-specific IgE antibody level proved that latex containing Foley catheter had
      caused foreskin edema. All anesthesiologists should pay attention to latex
      allergy and interview all patients in detail in preanesthetic evaluation.

PMID- 15242044
TI  - [A case report of severe laryngeal edema which occured before removal of a
      laryngeal mask airway].
AB  - A 41-year-old woman was scheduled for a partial hip arthroplasty. She was
      suffering from malignant rheumatoid arthritis for a long time and we recognized
      her difficult airway. After epidural catheterization, anesthesia was induced with
      fentanyl, thiopental, and 5% sevoflurane with oxygen. A laryngeal mask airway
      (LMA ; size 3) was inserted smoothly on third trial after suxamethonium chloride
      administration. Anesthesia was maintained with fentanyl, vecuronium bromide,
      sevoflurane with oxygen and epidural anesthesia. No complications were observed
      during the operation. After reversal of muscle relaxant, spontaneous respiration
      returned. But inspiratory stridor and chest wall retraction occurred soon, and we
      found severe epiglottic edema by bronchoscopy. A tracheal tube (ID 5.5 mm) was
      intubated immediately through the LMA. Twenty hours later the pharyngeal edema
      was still very severe, and tracheotomy was performed. The edema disappeared three
      days later. We thought the edema had occurred as a result of blood flow
      disturbance caused by LMA in narrow pharyngeal space expanding to the epiglottis.
      It should be kept in mind that severe edema could develop after LMA in malignant
      rheumatoid arthritis.

PMID- 15242045
TI  - [A case of giant thyroid tumor with tracheal stenosis].
AB  - A 61-year-old female underwent resection of a giant thyroid tumor, and tracheal
      stenosis ensued. She had cough, dyspnea, and palpitation in the supine position.
      The giant thyroid tumor was of the size of 11 x 12 cm and the diameter of trachea
      was 8 x 6 mm at 3.5 cm below the vocal cord, at which point the trachea was the
      narrowest on cervical computed tomography. The peak expiratory flow rate from the
      flow-volume curve was 2.94 l x sec(-1) (% predicted value 55.2%) in the upright
      position. We were concerned about difficult airway management. Oro-tracheal
      intubation with an armored tube (ID 7.5 mm) was performed after intravenous
      midazolam 2 mg and fentanyl 50 microg, 4% lidocaine spray 2 ml with oxygen 6 l x
      min(-1) inhalation keeping spontaneous breathing and consciousness. Anesthesia
      was induced and maintained with intravenous propofol, fentany, vecuronium and
      nitrous oxide in oxygen to keep the bispectral index between 40 and 60. The
      extracted thyroid tumor was 620 g in weight. A careful preoperative evaluation of
      the airway using ultrasonography, CT, MRI, laryngoscopy, bronchoscopy and
      respiratory function test, especially peak expiratory flow rate of the flow
      volume curve is important in such a case of a giant thyroid tumor. Intubation
      under conscious sedation with midazolam and fentanyl is useful for a patient with
      a giant thyroid tumor and tracheal stenosis.

PMID- 15242046
TI  - [Anesthetic management using HemoSonic 100 in a patient with chronic renal
      failure and dilated cardiomyopathy].
AB  - Anesthetic management for nephrectomy using HemoSonic 100, was performed in a
      patient with chronic renal failure and dilated cardiomyopathy (DCM). Anesthesia
      was induced and maintained with infusion of propofol and ketamine, and
      intermittent administration of fentanyl. During the surgery left ventricular
      ejection time (LVETc) decreased due to active bleeding from the renal artery.
      LVETc provided useful information for adequate preload and rate of transfusion in
      this case. Anesthesia and operation were finished successfully with relatively
      stable circulatory condition. We conclude that HemoSonic 100 is a useful monitor
      in anesthetic management of a patient with DCM, especially for the assessment of
      adequate preload.

PMID- 15242047
TI  - [Refractory generalized convulsions in a patient undergoing brain tumor resection
      during propofol anesthesia].
AB  - Propofol has been used to treat convulsions, while the drug is known to induce
      convulsions. We described a case of generalized convulsions during brain tumor
      resection under propofol anesthesia. A 24-year-old man was scheduled to undergo
      brain tumor resection. He had no history of epilepsy. Anesthesia was induced and
      maintained with propofol and fentanyl. During the craniotomy, the patient
      developed generalized convulsions. Diazepam, thiamylal, and phenytoin were given
      intravenously and the seizure activity resolved. Generalized convulsions recurred
      three times during the operation. Postoperative course was uneventful. On the 16
      th postoperative day, the patient underwent ventriculoperitoneal shunt under
      general anesthesia using sevoflurane, nitrous oxide and oxygen. Convulsions were
      not noted intra- and postoperatively. Because convulsions did not occur during
      sevoflurane anesthesia and the patient had no history of epilepsy, propofol may
      have induced a generalized convulsions on the first operation.

PMID- 15242048
TI  - [Anesthetic management of two patients with Brugada-type ECG and of different
      clinical severity].
AB  - Brugada syndrome is an arrhythmia syndrome characterized by typical
      electrocardiogram (Brugada-type ECG) and development of ventricular fibrillation
      (Vf) without any distinct structural heart diseases. The essential goal in the
      management of Brugada syndrome is to avoid the development of Vf. However, there
      has been no established consensus on pre-operative risk assessment of patients
      with Brugada-type ECG. We recently experienced two cases of anesthetic
      managements for patients with Brugada-type ECG. Based on these experiences and
      recent cardiological progress on the risk stratification of Brugada syndrome, we
      thoroughly discuss on the peri-operative managements for patients with Brugada
      type ECG.

PMID- 15242049
TI  - [Epidemiological study of hepatitis B and C in 34,336 patients operated at
      Hiroshima Prefectural Hospital during the period from 1993 to 2000].
AB  - BACKGROUND: We have many chances to deal with blood transfusion in the operation
      room, and it is important for us to pay more attention to prevent hospital
      infection. METHODS: We surveyed epidemiologically the prevalence of hepatitis B
      virus surface antigen (HBV) and hepatitis C virus antibody (HCV) in 34,336
      patients operated at Hiroshima Prefectural Hospital from April 1993 through March
      2001. RESULTS: The prevalence of HBV seropositivity was 1.8% in total, 1.6% in
      scheduled, and 2.5% in emergent cases. The prevalence of HCV seropositivity was
      7.1% in total, 6.8% in scheduled, and 8.0% in emergent cases. Prevalences of both
      of them in emergent cases were higher than scheduled. The prevalence of HBV was
      highest (3.4%) in patients with age of 40's, and the prevalence of HCV increased
      with age. The prevalences of HBV and HCV were highest (4.5% and 19.0%) in the
      division of surgery and dialysis-kidney disease center. CONCLUSIONS: It is
      important to carry out standard precautions for all patients to prevent hospital
      infection. Furthermore, we should pay attention to emergent operative cases and
      operative cases in dialyzed patients.

PMID- 15242050
TI  - [Present state of guidelines for perioperative management of deep vein thrombosis
      and pulmonary embolism in Japan].
AB  - To clarify the present state of local institutional guideline for perioperative
      deep thrombosis and pulmonary embolism in individual hospitals, a questionnaire
      was sent to anesthesia departments in Japan. According to the replies, 82
      hospitals have original guidelines. Forty of them reported the contents of their
      guidelines. However, 37 hospitals have some problems regarding their guidelines.
      Cost for these perioperative managements and application of spinal or epidural
      anesthesia for heparinized patients appears to be commonly recognized as pending
      questions in their guideline. It seems to be difficult to make a stereotyped
      standard guideline in Japan because each local guideline has a specific strategy
      according to their situations. However, it is needless to say that a further
      nationwide survey and collaboration, and governmental support for these diseases
      would be required.

PMID- 15242051
TI  - [Morphogenesis and differentiation in Volvox].

PMID- 15242052
TI  - [Structure and function of the cytochrome b6f complex of oxygenic
      photosynthesis].

PMID- 15242053
TI  - [Structural basis of microtubule plus-end-tracking proteins].

PMID- 15242054
TI  - [Three dimensional structure of IRF-3 and its implication in signal
      transduction].

PMID- 15242055
TI  - [Intron mediated coupling mechanisms in gene expression].

PMID- 15242056
TI  - [Eukaryotic translation and nuclear events].

PMID- 15242057
TI  - [Impact of Drosophila protein interaction map].

PMID- 15242058
TI  - [The Albert Lasker Medical Research Awards for Dr. Robert G. Roeder's study on
      gene expression regulation].

PMID- 15242059
TI  - [Function of BioFilm prepared from DNA].

PMID- 15242060
TI  - [Recent progress of free-flow electrophoresis method and its application for
      proteomics].

PMID- 15242061
TI  - [Acquisition of foreign patents/priority right/Q&A].

PMID- 15242062
TI  - The estimated prevalence of hypospadias in Hokkaido, Japan.
AB  - BACKGROUND: Hypospadias is one of the most common congenital anomalies in the
      world. Recently, increases in the prevalence of hypospadias have been reported in
      various countries including Japan. In this study, we examined whether the
      prevalence of hypospadias in Hokkaido, Japan, increased or not, using
      standardized diagnostic criteria. We also investigated the degree of its
      severity. METHODS: We calculated prevalence of hypospadias using hospital records
      of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by
      dividing the number of patients obtained from hospital records by the number of
      births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per
      10,000 births, and did not significantly change (p=0.7). The average proportions
      of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively.
      The decrease in the proportion of the proximal type was statistically significant
      (p=0.05) for the entire time period, whereas the proportion of the distal type
      did not have a significant upward trend for the observed 13 years (p=0.1).
      CONCLUSION: No significant changes in the prevalence of hypospadias existed in
      Hokkaido.

PMID- 15242063
TI  - Trends in levels of cholesterol in Japanese children from 1993 through 2001.
AB  - BACKGROUND: Cardiovascular risk factors in children raise the possibility of
      cardiovascular disease later in life. We attempted to determine the current
      trends in cardiovascular risk factors among Japanese children. METHODS: We
      examined fifth-graders at all the elementary schools in Iwata city in Japan every
      year from 1993 through 2001. We examined 4,673 boys and 4,484 girls, aged 10-11
      years. Height, body weight, body mass index, and serum total cholesterol
      concentrations were measured. Regression analysis was used to evaluate the
      trends. The independent variable was the calendar year of the examination. The
      dependent variables were the anthropometric values and the serum total
      cholesterol concentration in each individual. The relationships between the year
      and the prevalence of hyperlipidemia and the prevalence of obesity were also
      examined. RESULTS: Both the heights of the girls and the body weights of the both
      sexes were positively associated with the year. The body mass index in both girls
      and boys also showed positive relationships with the calendar year. In addition,
      there was an increase in the prevalence of obesity. Concerning the levels of
      cholesterol, positive regression coefficients were shown between the total
      cholesterol concentration and the year in both sexes. Furthermore, there was an
      increase in prevalence of hyperlipidemia. CONCLUSION: These results indicate that
      during the past decade among Japanese children involved in the study, both the
      body mass index and the serum total cholesterol concentrations increased.

PMID- 15242064
TI  - Risk of adverse reproductive outcomes associated with proximity to municipal
      solid waste incinerators with high dioxin emission levels in Japan.
AB  - BACKGROUND: Great public concern about health effects of dioxins emitted from
      municipal solid waste incinerators has increased in Japan. This paper
      investigates the association of adverse reproductive outcomes with maternal
      residential proximity to municipal solid waste incinerators. METHODS: The
      association of adverse reproductive outcomes with mothers living within 10 km
      from 63 municipal solid waste incinerators with high dioxin emission levels
      (above 80 ng international toxic equivalents TEQ/m3) in Japan was examined. The
      numbers of observed cases were compared with the expected numbers calculated from
      national rates adjusted regionally. Observed/expected ratios were tested for
      decline in risk or peak-decline in risk with distance up to 10 km. RESULTS: In
      the study area within 10 km from the 63 municipal solid waste incinerators in
      1997-1998, 225,215 live births, 3,387 fetal deaths, and 835 infant deaths were
      confirmed. None of the reproductive outcomes studied here showed statistically
      significant excess within 2 km from the incinerators. However, a statistically
      significant peak-decline in risk with distance from the incinerators up to 10 km
      was found for infant deaths (p=0.023) and infant deaths with all congenital
      malformations combined (p=0.047), where a "peak" is detected around 1-2 km.
      CONCLUSION: Our study shows a peak-decline in risk with distance from the
      municipal solid waste incinerators for infant deaths and infant deaths with all
      congenital malformations combined. However, due to the lack of detailed exposure
      information to dioxins around the incinerators, the observed trend in risk should
      be interpreted cautiously and there is a need for further investigation to
      accumulate good evidence regarding the reproductive health effects of waste
      incinerator exposure.

PMID- 15242065
TI  - Association between smoking habits and tryptophan hydroxylase gene C218A
      polymorphism among the Japanese population.
AB  - BACKGROUND: Genetic polymorphisms have proposed a new insight in smoking
      behavior. Genes in serotonin system are one of the candidates because of
      serotonin's role in mood regulation. A polymorphism C218A in intron 7 of the
      tryptophan hydroxylase (TPH) gene has been hypothesized in relation to smoking
      predisposition. METHODS: We examined the association on two Japanese populations:
      one was from the first-visit outpatients of Aichi Cancer Center Hospital during 3
      month period between April and June, 2001 (N=591), and the second was from the
      examinees who attended a health checkup program supported by the Nagoya municipal
      government in 2000 (N=446). Written documents on informed consent were obtained
      and lifestyle questionnaires were recorded. TPH C218A genotypes were determined
      by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP)
      method. RESULTS: The frequencies of the C- and A-allele were 52% and 48%,
      respectively, which was in Hardy-Weinberg equilibrium. As for current smoking
      status, no associations were statistically observed. It was, however, indicated
      that smokers with A/A genotype started smoking earlier in their life. Among male
      health examinees, mean ages at starting smoking were 18.7 (A/A), 19.9 (C/A), and
      22.4 years (C/C), (P<0.01). Also, on the Aichi Cancer Center Hospital subjects
      aged 60 and older, mean ages were 19.0 (A/A), 20.2 (C/A), and 20.3 years (C/C)
      for males and 22.3 (A/A), 31.0 (C/A), and 33.0 years (C/C) for females (P<0.05).
      CONCLUSIONS: The present study demonstrated that the TPH C218A polymorphism in
      intron 7 had no association with current smoking status in Japanese population.
      The hypothesis of early smoking initiation of A/A genotype was partially in
      agreement.

PMID- 15242066
TI  - Sequential evaluation of the national medical expenditures for asthma care in
      Japan.
AB  - BACKGROUND: It has been reported that the prevalence of asthma is on the rise in
      various countries; but studies on its effects on national medical expenditures
      are scarce. METHODS: From the outcome of the "Estimates of National Medical Care
      Expenditures" and "Patient Survey" compiled by the Statistics and Information
      Department, Minister's secretariat, the Ministry of Health, Labour, and Welfare
      of Japan, medical expenditures on asthmatic patients in Japan were sequentially
      examined. RESULTS: It was found that the percentage of asthmatic patients to the
      general medical care expenditures has been on the steady increase. A closer
      examination revealed that the percentage of asthmatic outpatients receiving care
      increased while those receiving care as inpatients decreased. CONCLUSION: The
      relationships between the percentage of the number of asthmatic patients
      utilizing medical services and the expenditures for their care differed between
      inpatients and outpatients.

PMID- 15242067
TI  - [Recent advances of evaluation of the macular diseases].

PMID- 15242068
TI  - [Histopathologic study on cyclocryotherapy of human and monkey eyes].
AB  - PURPOSE: To evaluate the lesion and repair process of the ciliary body and
      adjacent tissues in glaucomatous human eyes and normal monkey eyes with
      cyclocryotherapy. METHODS: We used light and electron microscopy to observe the
      ciliary body and adjacent tissues in five glaucomatous human eyes and five normal
      monkey eyes which were given cyclocryotherapy. RESULTS: Five absolute
      glaucomatous eyes were given cyclocryotherapy from one and a half to 3 years
      before the enucleation. One eye had no coagulated spots on the ciliary process,
      but five eyes had coagulated spots on the pars plana. The pigment epithelial
      cells were atrophic or had disappeared, but non-pigment epithelial cells had
      proliferated by one or two layers. At the lesion of monkey pars plicata
      cyclocryotherapy up to three months, melanophage phagocytosed pigment epithelium
      and melanocytes accumulated, although the proliferation of non-pigment epithelial
      cells was seen. At the lesion of monkey pars plana cyclocryotherapy melanophage
      accumulation was also marked, although non-pigment epithelial proliferation was
      greater than in pars plicata cyclocryotherapy. CONCLUSION: As cyclocryotherapy is
      a blind therapy, it is uncertain and difficult to destroy the ciliary process
      precisely. The repair process continued up to three months after monkey
      cyclocryotherapy, but it took up to one year and 6 months after human
      cyclocryotherapy.

PMID- 15242069
TI  - [Macular thickness after cataract surgery in diabetic patients].
AB  - PURPOSE: Macular edema after cataract surgery is the main cause of unfavorable
      visual outcome and more common in diabetic patients. The objective of this study
      was to evaluate the time course of change in macular thickness in diabetic
      patients, compared with that in nondiabetic patients after uneventful cataract
      surgery. SUBJECTS AND METHODS: We examined 36 diabetic eyes and 30 nondiabetic
      controls preoperatively and 1, 3, 7, 30, 90, and 180 days postoperatively, using
      a Retinal Thickness Analyzer (RTA). Aqueous flare intensity and visual acuity
      were also measured. RESULTS: Macular thickening and an increase in aqueous flare
      were marked in diabetic eyes and controls on the first postoperative day. In
      nondiabetic patients, these subtle changes improved gradually and returned to
      near-normal within 6 months. In diabetic patients, prolonged and progressive
      macular thickening was observed 6 months after surgery. Macular edema in diabetic
      patients had a propensity to cause poorer 6-month visual acuity. CONCLUSIONS: RTA
      is useful for early detection of macular edema. Using RTA, we demonstrated that
      cataract surgery induced subclinical macular edema even in nondiabetic subjects
      and that progressive macular edema might cause poor visual outcome in diabetic
      patients.

PMID- 15242070
TI  - [A retrospective analysis of infection after corneal transplantation].
AB  - PURPOSE: We studied retrospectively the background of postoperative infection
      after corneal transplantation. METHODS: We reviewed the records of 753 eyes that
      had undergone corneal transplantation at Kyoto Prefectural University of Medicine
      or the Baptist Eye Clinic over a period of 6 years from April 1994 to March 2000.
      Patients who developed microbial keratitis after corneal transplantation were
      evaluated for the incidence of infection, age, the interval between
      transplantation and infection, microbiological etiology, the use of topical
      steroids, therapy, and complications. RESULTS: Follow-up after keratoplasty
      averaged 43.2+/-25.6 months (mean+/-standard deviation). Among 753 eyes examined,
      microbial keratitis developed in 27 eyes (3.6%), 14 eyes had bacterial, and 13
      had fungal infections. The ages at presentation were 51.4+/-21.5 years for
      bacterial infections, and 66.5+/-11.1 for fungal infections. The time intervals
      between transplantation and the onset of infection averaged 7.8+/-7.9 months for
      bacterial infections, and 24.2+/-17.2 for fungal infections. Infections in 7
      (50.0%) of the bacterial eyes were caused by methicillin-resistant Staphylococcus
      aureus (MRSA) or epidermidis (MRSE), and 9 (69.2%) of the fungal infections by
      yeast type fungus (8 were Candida species). At onset of keratitis, 3 (21.4%) of
      the bacterial eyes and 6 (46.2%) of the fungal eyes were treated with
      fluorometholone, and 11 (78.6%) of the bacterial eyes and 7 (53.8%) of the fungal
      eyes were treated with betamethazone or dexamethasone. The treatment duration
      until the focus of disappeared was 32.8+/-19.7 days for bacterial eyes, and
      74.8+/-56.3 for fungal eyes. Major complications associated with infection
      included corneal perforation in 2 eyes of both the bacterial (14.3%) and fungal
      (15.4%) eyes, graft rejection in 4 (28.6%) bacterial eyes and 1 (7.7%) fungal
      eye, there was no recurrence of infection in the bacterial eyes but there were 3
      (23.1%) cases of recurrence in the fungal eyes. CONCLUSIONS: Infection after
      corneal transplantation is opportunistic. Fungal infections occurred later than
      bacterial infections. Also in fungal infections, the mean age at presentation was
      higher and the recurrence of infection was more frequent.

PMID- 15242071
TI  - [Diagnostic value of interleukin-10 and interleukin-6 in the vitreous of
      intraocular malignant lymphoma patients].
AB  - OBJECTIVE: Recent data suggest that the concentration of interleukin-10 (IL-10)
      is higher than that of interleukin-6 (IL-6) in the vitreous of eyes of patients
      with non-Hodgkin's lymphoma. In this study, we evaluated the utility of measuring
      intravitreal IL-10 and IL-6 concentrations in the diagnosis of intraocular
      lymphoma. METHODS: Specimens of undiluted vitreous were collected at the time of
      pars plana vitrectomy and IL-10 and IL-6 concentrations were determined. Vitreous
      specimens were obtained from 5 patients with suspected intraocular lymphoma and
      10 patients with uveitis presumed to be unrelated to a neoplasm. RESULTS: In all
      5 patients eventually diagnosed with intraocular lymphoma, the vitreous IL-10
      concentration ranged from 3,040 to 11,200 pg/ml, and was higher than the vitreous
      IL-6 concentration in all cases. In 9 of the 10 patients with uveitis, the
      vitreous IL-10 concentrations ranged from less than 2 to 97 pg/ml, with an IL
      10/IL-6 ratio of less than 0.11. However, in the remaining case diagnosed as
      uveitis of unknown etiology, the vitreous IL-10/IL-6 ratio was greater than 1.
      CONCLUSION: Our data suggest that the measurement of vitreous IL-10
      concentrations would aid in the diagnosis of intraocular lymphoma.

PMID- 15242072
TI  - [Quality of life evaluation of age-related macular degeneration].
AB  - PURPOSE: To evaluate quality of life (QOL) characteristics and ophthalmic factors
      influencing QOL in age-related macular degeneration (AMD) patients. SUBJECTS AND
      METHODS: The subjects were 80 patients with AMD. An eye-disease specific QOL
      questionnaire, The 25-Item National Eye Institute Visual Function Questionnaire
      (VFQ-25), was administered. Results were compared with those of glaucoma or
      cataract patients and those of individuals without eye diseases. The VFQ-25 score
      was assessed according to visual acuity, absolute scotoma size, and disease type.
      Multiple regression analysis was used to evaluate ophthalmic factors influencing
      the QOL score. RESULTS: VFQ-25 scores were significantly lower in AMD patients
      than in all other groups. Scores of patients with visual acuity less than 0.1,
      with large absolute central scotoma, and bilateral exudative AMD were lower, for
      several items, than those of patients with visual acuity of 0.4 or more, those of
      patients without absolute scotoma, and those of bilateral atrophic AMD patients,
      respectively. Visual acuity and absolute central scotoma size influenced social
      functioning and mental health. The exudative form influenced mental health and
      critical print size influenced dependency. CONCLUSION: The VFQ-25-assessed QOL of
      AMD patients was lower than that of glaucoma or cataract patients. Visual acuity,
      absolute central scotoma and the existence of exudative AMD influenced the QOL in
      AMD patients.

PMID- 15242073
TI  - [A case of pseudotumor cerebri with improvement of vision after lumboperitoneal
      shunt].
AB  - BACKGROUND: Patients with pseudotumor cerebri, also called benign intracranial
      hypertension, generally have a favorable prognosis. However, this disorder can
      cause permanent, severe visual loss. To our knowledge, no reports have described
      in detail retinal damage resulting from pseudotumor cerebri. CASE: We report the
      case of a 26-year-old woman who presented with serious bilateral visual
      impairment, severe papilledema, and retinal edema in a wide area. She was
      diagnosed with pseudotumor cerebri. Because of her progressive visual loss and
      failed medical control, she underwent a lumboperitoneal shunt. After the
      operation, her visual acuity and visual field improved in her left eye and the
      retinal edema resolved, but residual pigment epithelial damage was observed. In
      the first-order component of multifocal electroretinogram, the amplitudes were
      reduced, and peak implicit times were prolonged in the nasal retina. CONCLUSION:
      Retinal damage caused by severe and long-standing retinal edema may contribute to
      the pathological mechanisms for visual loss as well as optic nerve damage. The
      course of visual function in our case was important for diagnosis and therapeutic
      decisions. Because a poor visual outcome may result from pseudotumor cerebri, an
      ophthalmologist should closely monitor visual loss and visual function.

PMID- 15242074
TI  - Different clinical and coronary angiographic findings according to ratios of
      total cholesterol to high-density lipoprotein cholesterol during the acute phase
      of myocardial infarction.
AB  - OBJECTIVES: Several pathological studies have shown that a higher ratio of the
      serum total cholesterol concentration to the high-density lipoprotein cholesterol
      concentration (TC/HDL-C ratio) is associated with plaque rupture in patients with
      acute coronary syndromes. We examined the relationship between the serum total
      cholesterol concentration and the TC/HDL-C ratio, and clinical and angiographic
      findings in patients with first acute myocardial infarction. METHODS: Two hundred
      eighty patients were classified into quartiles according to the TC/HDL-C ratio
      measured within 24 hr from symptom onset: 70 patients in the first quartile
      (group L: mean TC/HDL-C ratio, 3.0), 140 in the second and third quartiles (group
      M: mean TC/HDL-C ratio, 4.6), and 70 in the fourth quartile (group H: mean TC/HDL
      C ratio, 7.5). RESULTS: There were no differences among the three groups with
      regard to sex, diabetes mellitus or hypertension. Patients in group L were older
      (66 +/- 9 vs 60 +/- 11, 56 +/- 10 years, p < 0.01) and had a higher incidence of
      stable angina before acute myocardial infarction (26% vs 14%, 10%, p < 0.05) than
      in patients groups M and H. Although coronary angiograms revealed no difference
      in the number of diseased vessels among the three groups, extent index indicating
      the proportion of each coronary segment that appears angiographically abnormal
      was lowest in group L (0.7 +/- 0.5), followed by group M (1.3 +/- 0.6), and high-
      est in group H ( 1.7 +/- 0.6, p < 0.01). The number of segments with
      calcification and the incidence of calcification in the culprit lesion were
      higher in group L than in groups M and H. CONCLUSIONS: Our findings suggest that
      the clinical presentations and angiographic appearances differ according to the
      TC/HDL-C ratio in the acute phase of acute myocardial infarction.

PMID- 15242075
TI  - [Diagnosis of vascular complications at the puncture site after cardiac
      catheterization].
AB  - OBJECTIVES: Cardiac catheterization is increasingly used for the diagnosis or
      treatment of coronary artery disease. Previous studies that revealed the
      incidence of complications such as arteriovenous fistula and pseudoaneurysm were
      based on retrospective analysis of cohorts referred to vascular surgery. This
      study was designed to determine the incidence of arteriovenous fistula and
      pseudoaneurysm after percutaneous transluminal angiography. METHODS: All 557
      consecutive patients undergoing cardiac catheterization were examined by
      ultrasonography from March 1, 2001 to April 1, 2002, to investigate the
      occurrence of arteriovenous fistula and pseudoaneurysm at the puncture site.
      RESULTS: Pseudoaneurysm was found in 16 patients (2.9%), and arteriovenous
      fistula in 12 patients (2.2%). Pseudoaneurysm in 7 patients (43.8%) and
      arteriovenous fistula in 6 patients (50.0%) were diagnosed only by ultrasonic
      examination. There were more female patients (9 patients, 56.3%) than male with
      pseudoaneurysm (p < 0.01). The puncture site was located after the division of
      the deep femoral artery and superficial femoral artery in all patients with
      complications. CONCLUSIONS: Ultrasonic examination was useful for diagnosis of
      complications such as arteriovenous fistula and pseudoaneurysm after cardiac
      catheterization.

PMID- 15242076
TI  - [Aortic root replacement using an allograft for active infective endocarditis
      with periannular abscess: single center experience].
AB  - OBJECTIVES: Results of aortic root replacement using an allograft for active
      infective endocarditis in the aortic position and periannular abscess were
      studied. METHODS: Aortic root replacement using a cryopreserved aortic allograft
      was performed 13 times in 12 patients (9 men, 3 women, mean age 52.8 years) at
      Saitama Medical School. Allografts were obtained from the Tokyo University Tissue
      Bank. Infection affected the prosthetic valve in 6 patients and the native valve
      in 7. Causative organisms were Staphylococci in 7 patients, Streptococci in 2,
      and unknown in 4. New York Heart Association functional class was II in 2
      patients, III in 3, and IV in 8. Six patients required inotropic support. Four
      were mechanically ventilated. Two were in a state of profound shock. Four had
      multiple organ failure. Surgery was conducted under hypothermic cardiopulmonary
      bypass and cardioplegic arrest. Allograft was sewn into place by monofilament
      continuous sutures. Carrel patch technique was used for coronary artery
      reconstruction. Five patients underwent concomitant procedures (replacement of
      the ascending aorta in 2 patients, coronary artery bypass grafting in 1, mitral
      valve repair in 1, pulmonary artery reconstruction in 1). RESULTS: Duration of
      surgery, cardiopulmonary bypass, and aortic clamping were 507 +/- 154, 307 +/-
      111, and 189 +/- 49 min, respectively. Two patients required intraaortic balloon
      pumping, and one required percutaneous cardiopulmonary support. Two patients in a
      state of shock died(hospital mortality: 15.4%). Duration of mechanical
      ventilation was 2.9 +/- 3.7 days. Intensive care unit stay was 4.6 +/- 5.5 days,
      and hospital stay was 61 +/- 26 days. One patient died of cancer 18 months later.
      One patient required reoperation 11 months later. Including operative death
      cases, cumulative survival at 2 years was 66.5% and freedom from cardiac events
      was 72.7%. CONCLUSIONS: Aortic root replacement with an allograft yielded
      acceptable clinical results.

PMID- 15242077
TI  - ["Chestnut-shaped" transient regional left ventricular hypokinesis with abnormal
      myocardial fatty acid metabolism, not corresponding to the coronary artery
      territories: a case report].
AB  - A 79-year-old female patient, who was initially suspected to have pneumonia, was
      admitted to the respiratory department of our hospital. She experienced chest
      pain on the second admission day. Electrocardiography showed ST-segment elevation
      in leads V3 through V6, and echocardiography revealed hypokinetic left
      ventricular wall motion. Therefore, myocardial infarction was suspected. She was
      transferred to the coronary care unit. Heart catheterization was immediately
      performed. Coronary angiography showed no significant stenotic lesion. Left
      ventriculography showed regional hypokinesis of the anterior and posterior walls
      near the base and normokinesis in the apex. Iodine-123-beta-methyl-p-iodophenyl
      pentadecanoic acid (123-BMIPP)myocardial single photon emission computed
      tomography(SPECT) revealed inhomogeneous decrease in uptake, especially in the
      lateral wall, which did not correspond to any of the coronary artery territories.
      The echocardiographic asynergy was dramatically resolved after 1 week and the
      123I-BMIPP SPECT finding was normal at 3 months. Although the clinical course of
      this patient was similar to that of tako-tsubo-like left ventricular dysfunction,
      the shape of her left ventricle was not typical. Left ventriculography showed
      hypokinesis of the anterior and posterior walls near the base and normokinesis in
      the apex, appearing like a chestnut rather than a tako-tsubo.

PMID- 15242078
TI  - [Pheochromocytoma with reversal of tako-tsubo-like transient left ventricular
      dysfunction: a case report].
AB  - A 59-year-old male was admitted to the emergency department because of sustained
      chest oppression. Electrocardiography revealed J type ST depression and peaked T
      wave in leads II, III, aVF, and V4-V6. No stenosis was found in the coronary
      arteries by urgent coronary angiography. Left ventricular abnormal wall movement
      with akinesis in the base and hyperkinesis in the apical area was observed and
      improved on the 12th day. Myocardial scintigraphy with iodine-123
      metaiodobenzylguanidine showed completely defective images and decreased
      accumulation in the base with combined thallium-201 and iodine-123-beta-methyl-p
      iodophenyl-pentadecanoic acid. Myocardial biopsy on the 12th day disclosed
      contraction band necrosis. The diagnosis was catecholamine-induced cardiomyopathy
      caused by pheochromocytoma.

PMID- 15242079
TI  - [A 78-year-old man with old anterior myocardial infarction showing normalization
      of poor R-wave in precordial leads after persistent chest pain].

PMID- 15242080
TI  - Pharmacological assessment of composite arterial conduits using angiography early
      in the postoperative period.
AB  - OBJECTIVES: Muscular arteries are vulnerable to vasospasm unlike elastic
      arteries. Having developed experimental models of composite arterial grafts, we
      assessed and compared the responses of the grafts with different pharmacological
      agents using angiography early in the postoperative period. SUBJECTS AND METHODS:
      We harvested the internal thoracic artery (ITA) and brachial-median artery (BMA)
      from 10 sheep. BMA was used as an alternative to the radial artery. Each vessel
      was assessed histologically and morphologically. Then, a serial composite graft
      was constructed so that BMA was interposed. On postoperative day one or two,
      angiography was performed on the composite graft to measure the diameter of each
      vessel in response to phenylephrine (alpha-adrenergic receptor agonist),
      nitroglycerin+phenylephrine, and milrinone+phenylephrine. RESULTS: The BMA had a
      wide media layer which consisted of abundant smooth muscle cells. The combined
      intima and media were thicker in BMA than in ITA (p<0.01). After injection of
      phenylephrine, the BMA diameter decreased (2.5+/-0.4 mm to 1.9+/-0.3 mm, p<0.01),
      while the ITA diameter remained unchanged (3.7+/-0.2 mm to 3.6+/-0.2 mm).
      Continuous infusion of nitroglycerin or milrinone prevented phenylephrine-induced
      vasoconstriction of the BMA (p<0.05). CONCLUSIONS: These results suggest that
      muscular arteries have a more pronounced vasoconstrictive response to alpha
      adrenergic receptor agonists than the elastic arteries. To avoid potential
      decrease in graft flow of muscular artery, it is advisable to use a vasodilator
      nitroglycerin or milrinone early in the postoperative period.

PMID- 15242082
TI  - Management of air leak after pulmonary resection.
AB  - OBJECTIVE: We prospectively evaluated the efficacy of water seal in the
      management of air leak after pulmonary resection. METHODS: Eighty-seven patients
      who underwent lobectomy were enrolled. Air leak was qualitatively described on
      each postoperative day using a six-grade scale. All chest tubes were continuously
      suctioned at a negative pressure of 12 cm H2O until the morning of postoperative
      day (POD) 1. Switch was made to water seal if the air leak was graded as "minor
      at expiration" or lower. This procedure is referred to as "the water seal
      challenge". RESULTS: On POD 1, 58 patients had air leaks. The water seal
      challenge was attempted on POD 1.6+/-1.0. While 45 patients (78%) continued to
      receive the water seal, the remaining 13 patients were switched to suctioning at 
      5 cm H2O followed by the successful second water seal challenge within 3 days
      from the first challenge. The air leak stopped 3.1+/-3.0 days after the
      application of the water seal in the 58 patients. None of the following
      correlated with the duration of air leak: preoperative pulmonary function tests,
      type of lobectomy, age, and gender. Only the leak grade on POD 0 correlated
      significantly with the duration of air leaks (p<0.0001). CONCLUSION: These
      results show that water seal is a safe and effective management option for air
      leak during the early postoperative period.

PMID- 15242081
TI  - Comparison of limited and full sternotomy in aortic valve replacement.
AB  - OBJECTIVE: The practice of minimally invasive valve surgery remains
      controversial. The aim of this study was to evaluate the technical feasibility
      and postoperative course of aortic valve replacement through limited upper
      sternotomy compared to conventional full sternotomy. METHODS: From May 1998 to
      August 2000, we performed 24 cases of isolated aortic valve replacements through
      the limited upper sternotomy approach (group M). During the same period, 18
      patients received isolated aortic valve replacements through the conventional
      full sternotomy approach (group C). Operation duration, postoperative course and
      laboratory data were compared between the two groups. RESULTS: All patients
      received a valve replacement with a prosthetic valve. There was no significant
      difference between the two groups in mean aortic cross-clamping time, mean
      cardiopulmonary bypass time or mean operation duration (skin to skin). No patient
      required blood transfusion. Patients in the group M were extubated earlier, with
      less postoperative blood loss and discharged earlier after the operation than
      those in group C. On the first postoperative day, the peak level of lactic acid
      dehydrogenease was significantly lower in the group M than those in group C.
      CONCLUSION: Limited upper sternotomy for aortic valve replacement resulted in
      shorter operation duration and minimized operative risks for the patients. We
      believe this method brings not only cosmetic benefits but also improved
      postoperative course.

PMID- 15242083
TI  - Full-thickness chest wall reconstruction using autologous tissue grafts after
      resection of recurrent desmoid tumor.
AB  - We report the case of a 62-year-old woman with a recurrent desmoid tumor of the
      chest wall who successfully underwent a full-thickness chest wall resection as
      well as skeletal and soft tissue reconstruction. In chest wall reconstruction, we
      used various kinds of autologous tissue grafts, i.e. rib, fascia lata and the
      transverse rectus abdominis myocutaneous flap. Judging from the reconstructed
      wall's strength, shape and flexibility, as well as wound healing, it is possible
      to conclude that this combined procedure is feasible because benefits of the
      procedure outweigh the disadvantage of additional operations for harvests.

PMID- 15242084
TI  - Double switch with reversed Patrick-McGoon for corrected transposition of the
      great arteries with double outlet right ventricle.
AB  - A 4-year-old boy diagnosed with a double outlet right ventricle with
      transposition of the great arteries in a discordant atrioventricular connection.
      The anatomical characteristics of the ventriculoarterial relationships resulting
      from leftward deviation were quite similar to a mirror image of those in the
      malformation reported by Patrick and McGoon. Hence, it was most appropriate to
      perform the double switch operation associated with Patrick-McGoon's
      intraventricular rerouting and Senning's atrial switch. This intraventricular
      rerouting could be performed without damaging the conduction system because of
      existence of the anterior node. The cardiac catheterization 1 month after the
      operation showed no pressure gradient of the new reconstructed left ventricular
      outflow tract, good left ventricular function and no significant pressure
      gradient of the right ventricular outflow tract. The patient has been staying in
      class 1 of New York Heart Association for more than 3 years after the operation.

PMID- 15242085
TI  - Bilateral coronary arteriovenous fistulas with an oversize left coronary
      aneurysm.
AB  - We experienced an interesting case of bilateral coronary arteriovenous fistulas
      with coronary aneurysms (50 mm in the left and 10 mm in the right) developed in a
      66-year-old woman. The pathological findings of both left and right aneurysms
      were quite similar. Etiological and surgical considerations about coronary
      aneurysm based on this case are discussed.

PMID- 15242086
TI  - Intraoperative trans-mitral endoscopic resection of left ventricular tumor.
AB  - A successful resection of left ventricular tumor in an 82-year-old woman who had
      undergone coronary artery bypass grafting ten years ago is presented. In an
      attempt to make a procedure less invasive, we chose a trans-mitral endoscopic
      resection with minimum dissection because of reoperation on patient of advanced
      age. With the use of cardiopulmonary bypass and cardioplegic protection, the
      right side of left atrium was incised longitudinally. The endoscope was inserted
      in the ventricle via the mitral valve. A stalk of the tumor was cut by snare
      strangulation and the whole tumor was extracted endoscopically. The postoperative
      course was uneventful. To our best knowledge, this is the first report on
      endoscopic resection of the left ventricular tumor via a mitral valve. This
      method appear to be the choice in resecting the left ventricular tumor.

PMID- 15242087
TI  - Long-term survival after surgical resection of liver metastasis from lung cancer.
AB  - Lung cancer metastasis to the liver indicates a poor prognosis, and the majority
      of patients with metastatic disease to the liver are not indicated for surgery
      because of the number or distribution of metastases or the presence of
      extrahepatic disease. We herein describe a case of long-term survival after a
      surgical resection of liver metastases from lung cancer. Six months after surgery
      for Stage IB primary lung adenocarcinoma, a 71-year-old male was found to have a
      metastatic tumor in his liver. A hepatic resection for the metastatic tumor and
      another small metastatic foci found intraoperatively was carried out, and the
      tumors were pathologically diagnosed as liver metastases from lung cancer. The
      patient is presently alive and well without recurrence, as of 5 years and 2
      months after the liver resection. This is the first report of the successful
      surgical treatment of liver metastasis from lung cancer.

PMID- 15242088
TI  - Esophageal perforation of aortic arch aneurysm treated free of mediastinitis
      without manipulating esophagus.
AB  - Esophageal perforations of thoracic aortic aneurysms are most likely to be fatal.
      Patients with aortoesophageal fistula require urgent operation on both the
      esophageal perforation site and the aortic lesion to avoid terminal
      exsanguination and uncontrollable mediastinitis. We present a case of 71-year-old
      woman suffering esophageal perforation of aortic arch aneurysm with sentinel
      arterial hemorrhage, who has not developed patent aortoesophageal fistula.
      Computed tomography verified rupture of aortic arch aneurysm that had eroded the
      esophagus. She underwent successful graft replacement and remains well without
      signs of mediastinitis over one year after the event. It is possible, in selected
      cases of esophageal perforation of thoracic aortic aneurysm, to manage the
      esophageal lesion without any surgical intervention, such as primary closure,
      omental coverage and surgical discontinuity to achieve esophageal healing free of
      infection.

PMID- 15242089
TI  - Prosthetic valve endocarditis due to Candida albicans treated successfully with
      medical treatment alone.
AB  - Prosthetic valve endocarditis (PVE) caused by Candida species is associated with
      high morbidity and mortality. A combination of surgical resection and antifungal
      drug therapy is the golden standard for treatment, yet surgical intervention is
      not possible in all cases of Candida PVE. We report a case of PVE due to Candida
      albicans cured by medical treatment alone. This case suggests that, in some
      instances, Candida PVE can be managed medically with antifungal therapy. Such a
      conservative approach should be applied with caution and necessitates very close
      follow-up on a long-term basis.

PMID- 15242090
TI  - Extraction of electrolytes from aqueous solutions and their spectrophotometric
      determination by use of acid-base chromoionophores in lipophylic solvents.
AB  - The formation of non-absorbing complexes in an organic phase has been exploited
      for the spectrophotometric determination of ionic analytes in aqueous solutions.
      The method is based on liquid-liquid extraction of aqueous solution with
      lipophylic organic phases containing an acid-base chromoionophore, a neutral
      lypophilic ligand (neutral carrier) selective to the analyte and a cationic (or
      anionic) exchanger. The method avoids all difficulties of the preparation of the
      very thin membranes used in optodes, so that it can advantageously be used for
      the study of the role physical-chemical parameters of the system in order to
      optimize them and to prepare, if necessary, an optimized optode. Two lipophylic
      derivatives of Nile Blue and 4',5-dibromofluorescein have been synthesized, in
      order to ensure their permanence within organic phase. Two different neutral
      carriers previously characterized by us as ionophores for liquid-membrane Ion
      Selective Electrodes have been employed. Three different ionic exchangers have
      been tested. Furthermore, a model allowing the interpolation of experimental data
      and the determination of the thermodynamic constant of the ionic-exchange
      equilibrium has been developed and applied.

PMID- 15242091
TI  - Polycyclic aromatic hydrocarbons in the atmosphere: monitoring, sources, sinks
      and fate. II: Sinks and fate.
AB  - This paper reviews the transformation processes that polycyclic aromatic
      hydrocarbons (PAHs) undergo in the atmosphere. These processes can take place
      both in the gas phase and in the particulate/aerosol one. Among the gas-phase
      processes, the most important ones are the daytime reaction with *OH and the
      nighttime reaction with *NO3. The relative importance of the two processes
      depends on the particular PAH molecule. For instance, gaseous naphthalene is
      mainly removed from the atmosphere upon reaction with *OH, while gaseous
      phenanthrene is mainly removed by reaction with *NO3. Oxy-, hydroxy-, and nitro
      PAHs are the main transformation intermediates. Reaction with ozone and
      photolysis play a secondary role in the transformation of gaseous PAHs. The
      particle-associated processes are usually slower than the gas-phase ones, thus
      the gas-phase PAHs usually have shorter atmospheric lifetimes than those found on
      particulate. Due to the higher residence time on particulate when compared with
      the gas phase, direct or assisted photolysis plays a relevant role in the
      transformation of particle-associated PAHs. Among the other processes taking
      place in the condensed phase, nitration plays a very important role due to the
      health impact of nitro-PAHs, some of them being the most powerful mutagens found
      so far in atmospheric particulate extracts.

PMID- 15242092
TI  - Evaluation of purification procedures of DNA from maize-meal samples by
      exploiting different analytical techniques for the assessment of DNA quality.
AB  - Two different approaches generally applied to achieve purification of DNA
      extracted from cells were compared: precipitation by organic solvents and
      enzymatic treatments. We investigated various experimental protocols reported in
      literature by evaluating DNA purity, integrity and yield. Reliability of
      analytical techniques normally employed to assess DNA purity and quantity was
      studied and comments and conclusions were suggested by comparing results obtained
      by different analytical techniques. Enzymatic treatments prove to be unable of
      increasing DNA purity while determining a significant degradation. In contrast,
      optimised conditions for solvent precipitation enabled a sharp increase of DNA
      purity to be obtained, associated with the maintenance of the initial DNA
      integrity. The application of the optimised protocol to maize-meal samples
      allowed us to achieve a good PCR amplification even with those samples which gave
      poor amplification by following the protocol recommended by the Italian
      legislation in force for GMO detection in food.

PMID- 15242093
TI  - Characterization of n-alkanes and PAHs in PM10 samples in Prato (Italy).
AB  - This study reports the characterization of n-alkanes and PAHs in 13 PM10 samples
      collected in the South area of Prato (Italy) during the period April-July 2002. n
      Alkanes concentrations ranged between 9.45 and 182.64 ng/mc while PAHs
      concentrations ranged from 3.058 to 22.048 ng/mc. No correlation was evidenced
      between benzo(a)pirene and PM10 concentrations. Total carbonaceous aerosol was
      also measured and it meanly accounted for 21.5% of the PM10 mass ranging from
      12.4% to 27.1%.

PMID- 15242094
TI  - The acidic constants of 2-hydroxybenzohydroxamic acid in NaClO4 solutions at 25
      degrees C.
AB  - The protolysis equilibria of 2-hydroxybenzohydroxamic acid, H2SAX, have been
      studied at 25 degrees C in different ionic media by potentiometric titration with
      a glass electrode. The media were 0.513, 1.05, 2.21 and 3.5 mol/kg NaClO4. The
      constants beta(-p)(H2SAX<==>H(2-p)SAX(-p)+pH+), combined with salting effects of
      NaClO4 on H2SAX deduced from solubility determinations, were processed by the
      specific interaction theory, SIT, to give equilibrium constants at infinite
      dilution, log beta(-1)(o) = -7.655 +/- 0.013 and log beta(-2)(o) = -17.94 +/-
      0.04, as well as specific interaction coefficients b(HSAX-,Na+) = 0.12 +/- 0.01
      and b(SAX2-,Na+) = 0.17 +/- 0.02, molal(-1).

PMID- 15242095
TI  - Effect of a contaminated site (the San Giuliano landfill, Venice, Italy) on the
      interaction between water bodies in a coastal aquifer system.
AB  - A complex multiple aquifer system affected by a contaminated site and exposed to
      tidal effects was investigated to develop the hydrogeological conceptual model of
      the study case. Two water bodies were identified, from top to down: a surface
      aquifer unaffected by tidal events, and a semiconfined aquifer partly
      communicating with the brackish lagoon waters. By using the Cl(-)/SO4(2-) ratio
      and the DOC (Dissolved Organic Carbon) concentration, as well as by applying the
      kriking to the piezometric levels results, the groundwater flow directions and
      the hydraulic gradients within the investigated aquifers were also identified.
      Based on the overall results, a schematic of the conceptual model for the whole
      aquifer system was provided which allows to visualize the communication between
      the different water bodies.

PMID- 15242096
TI  - Chemical and environmental implications of visible and near-infrared spectral
      features of salt crusts formed from different brines.
AB  - This work describes a laboratory experiment intended to study the formation and
      spectral reflectance properties of stratified salt crusts that cause severe
      environmental degradations to soil and water resources in arid regions. Salt
      crusts were prepared by evaporating three types of saline solutions consisting of
      i) NaCl - Na2SO4, ii) Na2SO4 - MgSO4, and iii) NaCl - MgSO4 at an initial
      concentrations of 50 mmol L(-1). They were examined for evaporite mineralogy
      using X-ray diffraction, optical and reflected microscopes, and for spectral
      reflectance with a high-resolution spectroradiometer (GER 3700) in the visible
      and near-infrared regions (400-2500 nm). The study documented chemical and
      environmental implications of the spectral properties of salt formed from the
      studied saline-systems. The reported results can be used to understand remotely
      sensed signatures of salt crusts and their implications.

PMID- 15242097
TI  - Three-stage sequential extraction procedure for metal partitioning in polluted
      soils and sediments.
AB  - The sequential extraction procedure proposed by the Standard, Measurements and
      Testing program "SM&T" of the European Union has been applied to evaluate the
      amounts of Cr, Cu, Mn, Ni, Pb and Zn, extracted at each stage and indirectly
      their mobility and bioavailability in soil and sediment samples from a polluted
      area. Analysis of the extracts was carried out by flame atomic absorption
      spectrometry (FAAS). No significant matrix interferences were found except for Cr
      in the acetic acid and hydroxylammonium chloride extracts, which required
      determination by the standard additions method. Both of soils and sediments
      studied show similar partitioning of Mn, Ni, Cu and Cr. Mn and Ni can be
      considered to have significant component bound to the acido-soluble fraction,
      whereas, Cr and Cu occur largely in the organic and residual phases. The
      partitioning of Pb and Zn was different between soil and sediment. In terms of
      mobility and bioavailability, in soils, Ni and Mn can be regarded as moderately
      available followed by a lower availability of Pb while Cu, Zn and Cr have a very
      limited availability. In sediments, a higher availability (short-medium term) of
      Mn and Zn was presumed followed by a lower availability of Ni and Pb, whereas, Cu
      and Cr, occurring largely in the organic and residual phases, were of very
      limited availability.

PMID- 15242098
TI  - Application of voltammetric methods for the analysis of gold and other transition
      metals in quartzite rock.
AB  - Simple, rapid and accurate voltammetric methods viz. DCP, DPP and DPASV have been
      presented for the trace determination of gold and other transition metals in
      quartzite rock sample. The analysis has been performed using 0.1 M(NH4)2
      tartrate, 0.1 M NaClO4 and 1 M NaOH as supporting electrolyte with 0.001% gelatin
      as maximum suppressor. The results show the presence of CuII(10.70), CoII(4.72),
      FeIII(66.96), AuIII(0.066), ZnII(1.68) and CdII(0.62) mg x g(-1) metal ions from
      the sample. Gold produced a well defined wave/peak with E1,2/Ep = -0.61 V/-0.64 V
      vs SCE, in 1 M NaOH supporting electrolyte. The quantitative analysis of metal
      inos was carried out by the method of standard addition. Statistical treatment of
      the observed voltammetric data reveals high accuracy and good precision of
      determination. The observed voltammetric results are comparable with those
      obtained using AAS method.

PMID- 15242099
TI  - Extractive spectrophotometric determination of tungsten(VI) using 3-hydroxy-2-(2'
      thienyl)-4-oxo-4H-1-benzopyran.
AB  - A simple, rapid, highly sensitive and selective spectrophotometric method for the
      determination of tungsten(VI) in trace amounts is developed using 3-hydroxy-2-(2'
      thienyl)-4-oxo-4H-1-benzopyran (HTB) as a reagent for the complexation of metal
      ion and extracting the 1:2 (metal:ligand) complex into dichloromethane from 0.2 M
      HCl solution. It obeys Beer's law in the range 0-2.8 microg Wml(-1) with molar
      absorptivity and Sandell's sensitivity at 415 nm as 6.45 x 10(4) L mol(-1) cm(-1)
      and 0.0029 microg W(VI) cm(-2), respectively. The method is free from the
      interference of a large number (39) of elements and handles satisfactorily the
      analysis of various samples of varying complexity.

PMID- 15242100
TI  - Neptunium-237 determination in depleted uranium ammunition by alpha spectrometry.

PMID- 15242101
TI  - Aquaporins: water channel proteins of the cell membrane.
AB  - Aquaporins (AQP) are integral membrane proteins that serve as channels in the
      transfer of water, and in some cases, small solutes across the membrane. They are
      conserved in bacteria, plants, and animals. Structural analyses of the molecules
      have revealed the presence of a pore in the center of each aquaporin molecule. In
      mammalian cells, more than 10 isoforms (AQP0-AQP10) have been identified so far.
      They are differentially expressed in many types of cells and tissues in the body.
      AQP0 is abundant in the lens. AQP1 is found in the blood vessels, kidney proximal
      tubules, eye, and ear. AQP2 is expressed in the kidney collecting ducts, where it
      shuttles between the intracellular storage sites and the plasma membrane under
      the control of antidiuretic hormone (ADH). Mutations of AQP2 result in diabetes
      insipidus. AQP3 is present in the kidney collecting ducts, epidermis, urinary,
      respiratory, and digestive tracts. AQP3 in organs other than the kidney may be
      involved in the supply of water to them. AQP4 is present in the brain astrocytes,
      eye, ear, skeletal muscle, stomach parietal cells, and kidney collecting ducts.
      AQP5 is in the secretory cells such as salivary, lacrimal, and sweat glands. AQP5
      is also expressed in the ear and eye. AQP6 is localized intracellular vesicles in
      the kidney collecting duct cells. AQP7 is expressed in the adipocytes, testis,
      and kidney. AQP8 is expressed in the kidney, testis, and liver. AQP9 is present
      in the liver and leukocytes. AQP10 is expressed in the intestine. The diverse and
      characteristic distribution of aquaporins in the body suggests their important
      and specific roles in each organ.

PMID- 15242102
TI  - Surviving the heat. At Senate, House hearings, lawmakers ask tough questions of
      high-profile execs regarding tax-exemption status, charity.
AB  - After hospital executives trooped to Capitol Hill hearings last week to defend
      their billing and collection practices for the uninsured, the threat of immediate
      action to regulate pricing and charity care seemed to pass. The AHA's David
      Bernd, left, argued that not-for-profits' mission is much wider than just
      indigent care.

PMID- 15242103
TI  - Specialty hospitals. Exception to the rule. CMS' exemption of specialty hospital
      good news for other in-progress facilities.

PMID- 15242104
TI  - Specialty care. A matter of antitrust? Justice Department probes deal to split
      cancer and heart services.

PMID- 15242105
TI  - Managed care. New call for patients' bill of rights. Docs worry ruling limiting
      HMO suits will boost medical malpractice filings.

PMID- 15242106
TI  - Quality. Sharper image. OSHA enforces bloodborne pathogen standards.

PMID- 15242107
TI  - Physicians. Paying the price. Practices consider surcharges to combat high cost
      of malpractice insurance.

PMID- 15242108
TI  - Suppliers. Stents to be tested on diabetics.

PMID- 15242109
TI  - Medicaid. Offering some relief to states. Bill would extend temporary solution
      for Medicaid programs.

PMID- 15242110
TI  - Insurers. Like a locomotive. Insurer protected rail clerks, now setting IT
      standards.

PMID- 15242111
TI  - Patient-friendly billing--the sequel. Providers are doing their best to serve the
      uninsured amid uncertain rules.

PMID- 15242112
TI  - Planning for day after tomorrow. Hospitals taking a longer-range look at capital
      consumption, with return on investment becoming a top priority.

PMID- 15242113
TI  - Taking IT to the Hill. Trade groups send troops to Washington to serve in
      educational, promotional roles as IT becomes a high-profile legislative issue.

PMID- 15242114
TI  - Strong nitrogenous and agro-wastewater. Foreward.

PMID- 15242115
TI  - Reject water: treating of process water in large wastewater treatment plants in
      Germany--a case study.
AB  - The increase of the hydraulic loading of a municipal wastewater treatment plant
      caused by the sludge dewatering process is of minor importance. However, the
      rejected nitrogen load accounts for up to 25% of the nitrogen load in the raw
      sewage. As a result, the process water significantly influences the stage volume
      of the biological treatment steps. Rejection management can prevent critical
      nitrogen concentrations in the effluent of the plant. In some cases, the treating
      capacity must be increased. Separate treatment of the process water can be an
      alternative to the enlargement of the main wastewater treatment stages. This
      article describes the compositions of the process waters from different sludge
      treatment steps, the influence on the main wastewater treatment steps, possible
      strategies to handle the rejection problem, and processes for separate treatment
      of the sludge liquor. Some results of a German case study on large wastewater
      treatment plants illustrate the situation concerning separate process water
      treatment in Germany. These results suggest that side stream treatment can be a
      practical alternative to a classic increase in the length of the main stream
      stages. Moreover, they prove that many different processes are useful for the
      separate treatment of sludge liquor.

PMID- 15242116
TI  - Investigation of the effect of free ammonia concentration upon leachate treatment
      by shortcut biological nitrogen removal process.
AB  - A shortcut biological nitrogen removal (SBNR) process was operated to treat an
      ammonium rich landfill leachate using a pilot-scale reactor. The SBNR process was
      intended to oxidize ammonia to nitrite and, then, to reduce it to nitrogen gas.
      When the hydraulic retention time was 4-3 days, a half of the ammonium oxidized
      was accumulated as nitrite in the oxidation tank. The nitrite was denitrified
      completely in the anoxic tank when recycled. The average free ammonia (FA)
      concentration in the ammonium oxidation tank was 3.7 mg/L. The specific substrate
      utilization rates of ammonium oxidizers and nitrite oxidizers were investigated
      at varying FA concentrations through batch experiments. The highest specific
      ammonium oxidation rate was observed when the FA concentration was 10 mg/L. The
      rate decreased slightly when the FA concentration was increased to 20 or 50 mg/L,
      or decreased significantly when it was 5 mg/L. In case of nitrite oxidation, the
      specific nitrite utilization rate decreased significantly with increasing FA
      concentration up to 10 mg/L. Consequently, the optimal FA concentration in
      leachate treatment was 10 mg/L for maximum nitrite accumulation and maximum
      ammonium removal, or 5 mg/L for lower ammonium concentration and reasonable
      nitrite accumulation.

PMID- 15242117
TI  - Nitrogen removal via nitrite from seawater contained sewage.
AB  - Under the control of both pH and the concentration of free ammonia (FA), the
      nitrification-denitrification via nitrite pathway was accomplished in SBR to
      achieve enhanced biological nitrogen removal from seawater contained wastewater,
      which is used to flush toilet, under relatively high salinity. Several parameters
      including salinity, temperature, pH, and NH4+-N loading rate were studied to
      evaluate their effects. The results indicate that at different salinity the
      nitrogen removal efficiency is relative to ammonia-nitrogen loading rate. The
      nitrogen removal efficiency reaches above 90% when the NH4+-N loading does not
      exceed 0.15 kg NH4+-N/kg MLSS d. With the salinity increasing, the ammonia
      nitrogen loading rate should be lowered to obtain high removal efficiency. The
      evaluation of temperature effect shows that nitrogen removal efficiency is
      promoted twice when reaction temperature is elevated from 20 to 30 degrees C.
      Moderately high pH in the range of 7.5-8.5 has advantage to achieve effective
      nitrification-denitrification via nitrite, the process of which is caused by the
      selective inhibition of free ammonia (FA).

PMID- 15242118
TI  - Advanced treatment of biotreated textile industry wastewater with ozone,
      virgin/ozonated granular activated carbon and their combination.
AB  - Biotreated textile wastewater (CODo = 248 mg L(-1); TOCo = 58 mg L(-1); A620 =
      0.007 cm(-1); A525 = 0.181 cm(-1); A436 = 0.198 cm(-1)) was subjected to advanced
      treatment with ozonation, granular activated carbon (GAC) adsorption in serial
      and simultaneous applications. Experiments were conducted to investigate the
      effects of applied ozone dose, ozone absorption rate, specific ozone absorption
      efficiency, GAC dose, and reaction pH on the treatment performance of the
      selected tertiary treatment scheme. In separate experiments, the impact of virgin
      GAC ozonation on its adsorptive capacity for biotreated and biotreated + ozonated
      textile effluent was also investigated. Ozonation appeared to be more effective
      for decolorization (kd = 0.15 min(-1) at pH = 3), whereas GAC adsorption yielded
      higher COD removal rates (54% at pH = 3). It was also found that GAC addition (4
      g/L) at pH = 7 and 9 enhanced the COD abatement rate of the ozonation process
      significantly and that the sequential application of ozonation (at pH = 3-11, 675
      mg L(-1) O3) followed by GAC adsorption (at pH = 3-7, 10 g L(-1) GAC) resulted in
      the highest treatment performances both in terms of color and COD reduction.
      Simultaneous application of GAC and ozone at acidic and alkaline pH seriously
      inhibited COD abatement rates as a consequence of competitive adsorption and
      partial oxidation of textile components and GAC. It could also be established
      that ozone absorption efficiency decreased after color removal was complete.
      Ozonation of biotreated textile wastewater with 113 mg L(-1) ozone resulted in an
      appreciable enhancement of GAC adsorptive capacity in terms of residual color
      removal. Ozonation of GAC at relatively low doses (= 10.8 mg/g GAC) did not
      improve its overall adsorption capacity.

PMID- 15242119
TI  - Effects of pH and substrate on the competition between glycogen and phosphorus
      accumulating organisms.
AB  - This article evaluates effects of pH and substrate on the competition between
      glycogen (GAOs) and phosphorus accumulating organisms (PAOs). A sequencing batch
      reactor system was operated for enhanced biological phosphorus removal (EBPR)
      with acetate as the sole carbon source and acetate added domestic wastewater at
      different influent acetate/phosphate ratios. Some batch tests were performed
      using acetate added domestic wastewater at different influent acetate, phosphate
      ratios, with different initial pH values of acetate and domestic wastewater
      mixture. The resulting experimental data supported the presence of GAOs for all
      tested HAC P ratios, especially under P limiting conditions for acetate as sole
      carbon source. Strong evidence is observed that acetate added domestic wastewater
      system had higher PAOs fraction than acetate system as sole source carbon, with
      using model components, namely substrate uptake, glycogen utilization and P
      release.

PMID- 15242120
TI  - Ozonation of nonbiodegradable organics in tannery wastewater.
AB  - The study explores the impact of ozonation on the fate of different soluble COD
      fractions in the tannery wastewater at different phases during the course of
      biological treatment, in order to identify the phase where ozonation is likely to
      generate the maximum beneficial effect on biological treatability. Samples from
      the biological treatment influent and from the mixed liquor at periods
      significant for the fate of COD fractions have been ozonated. Ozone treatment at
      the phase where the readily biodegradable COD component was biologically depleted
      is determined as the most promising alternative among others, since the highest
      COD removal efficiencies are achieved even with low feeding time of 5 min at the
      selected ozone flow-rate of 42.8 mg min. The merit of ozonation at this stage in
      the formation of simpler more biodegradable compounds deserves further attention.

PMID- 15242121
TI  - Improvement of activated sludge dewaterability by humus soil induced
      bioflocculation.
AB  - Effects of humus soil particles on the dewaterability of activated sludge were
      investigated. Cations leaching increased proportionally with the dosage of humus
      soil, and the leaching was not significant after 2 h. Divalent cations, Ca2+ and
      Mg2+, leaching from the humus soil played an important role in improving
      dewaterability of the biological sludge. On the contrary, dewaterability was not
      affected or slightly deteriorated by the monovalent cations, K+ and Na+ leached
      from the humus soil. Improvement in dewaterability of the sludge by addition of
      humus soil was higher than that of equivalent cations mixture. It seemed that the
      decrease of supracolloidal bio-particles (1 to 100 microm in diameter) resulted
      in diminishing of the blinding effect on cake and filter medium. SRF (specific
      resistance to filtration) of the humus soil added sludge varied in parallel with
      the M/D (monovalent to divalent cation) ratio, and the M/D ratio could be
      utilized as a useful tool for evaluation of the sludge dewatering
      characteristics. Long-term effects of humus soil on the improvement of activated
      sludge dewaterability were clearly identified by continuous operation results of
      a bench-scale MLE (Modified Ludzack Ettinger) system combined with a humus soil
      contactor. On the other hand, dewaterability of the control sludge was only
      slightly improved by a decrease in M/D ratio of the wastewater influent.

PMID- 15242122
TI  - Implementation of the Anammox process for improved nitrogen removal.
AB  - Stringent standards for nitrogen discharge necessitate the implementation of new
      systems for the sustainable removal of ammonium from wastewater. One of such
      systems is based on the process of anaerobic ammonium oxidation (Anammox), which
      is a new powerful tool especially for strong nitrogenous wastewaters. In this
      study, the Anammox process performance was tested with synthetic wastewater in a
      completely stirred tank reactor (CSTR). The reactor was operated for 511 days and
      fed with increasing amounts of ammonium and nitrite. In this period, an increase
      of ammonium and nitrite utilization rates were observed as a result of the
      increase of nitrogen loads in the influent. After 272 days, about 60% of the
      biomass was removed from the reactor and the system was restarted. Throughout 511
      days 90% of the ammonium and more than 99% of the nitrite were converted mainly
      to dinitrogen (N2) and nitrate. The microbial community in the reactor was
      characterized with Fluorescence in situ Hybridization (FISH). The study showed
      that the population in the reactor was dominated by the deep-branching
      planctomycete Candidatus "Brocadia anammoxidans" strain Dokhaven 2.

PMID- 15242123
TI  - Effects of mixture ratio and hydraulic retention time on single-stage anaerobic
      co-digestion of food waste and waste activated sludge.
AB  - The biochemical methane potential (BMP) test was used to evaluate the anaerobic
      biodegradabilities of food waste (FW), waste activated sludge (WAS), and the
      mixtures having the ratios of 10:90, 30:70, 50:50, 70:30, and 90:10 (FW:WAS) on a
      volatile solid (VS) basis. The carbon/nitrogen (C/N) ratio and the
      biodegradability of the mixtures improved from 6.16 to 14.14 and increased from
      36.6 to 82.6% as the FW proportion of the mixture increased from 10 to 90%,
      respectively. The stability and performance of the single-stage anaerobic
      digester (SSAD) for the co-digestion of FW and WAS were investigated, operated at
      the hydraulic retention times (HRTs) of 10, 13, 16, and 20 days with five
      mixtures at 35 degrees C, respectively. During all the experiments, there were no
      indication of failure such as low pH, insufficient alkalinity, ammonia
      inhibition, and the accumulation of volatile fatty acids (VFAs) in any of the
      digesters, and the buffer capacity was the highest in the digester fed with a
      feed mixture of 50:50. The optimum operating conditions of the SSAD were found to
      be an HRT of 13 days and a mixture of 50:50 in terms of the buffer capacity of
      the digester and the effluent VS concentration, the methane content of the biogas
      produced and the specific methane production (SMP). The VS removal efficiency,
      biogas production rate (GPR), and SMP in this condition achieved 56.8%, 1.24 m3
      m(-3) d(-1) and 0.321 m3 CH4 kg(-1) VS(fed)(-1) with an organic loading rate
      (OLR) of 2.43 kg VS m(-3) d(-1).

PMID- 15242124
TI  - Effects of fill time on the fractal dimension and size of floc for SBR treating
      low C/N ratio wastewater.
AB  - The aim of this study was to investigate the effects of fill time of influent on
      the physical characteristics of biological floc for sequencing batch reactor
      (SBR) treating low C/N ratio wastewater. The fractal dimension and size of floc
      were measured for characterizing floc. The fractal dimension of floc was analyzed
      by using Small Angle Laser Light Scattering (SALLS) method. SBR with short fill
      time showed higher removal efficiencies of COD, BOD, T-N, and T-P than with long
      fill time. Larger floc size and fractal dimension were generated at SBR with
      short fill time. Short fill time generated the sludge with better settling and
      thickening properties. Alternating anaerobic and aerobic condition in the cycle
      also affected the floc size and fractal dimension. The floc size decreased under
      anaerobic phase, and floc size increased under aerobic phase. During fill time,
      the fractal dimension of floc decreased. As the fill stop, the fractal dimension
      of floc increased. Therefore, the fill time condition more affected the fractal
      dimension of floc. More efficient nitrification and phosphorus release were
      observed during a cycle with short fill time operation.

PMID- 15242125
TI  - Removal of nitriles from synthetic wastewater by acrylonitrile utilizing
      bacteria.
AB  - This study describes the ability of two bacteria strains, isolated from an ABS
      resin manufacturing wastewater treatment system, to remove high acrylonitrile
      concentrations. Straight chain aliphatic nitrile compound (propionitrile, allyl
      cyanide); branch chain aliphatic nitrile compound (isobutyronitrilc) and aromatic
      nitrile compound (benzonitrile) removal by Comamonas testosteroni and Acidovorax
      sp. was also investigated. The results are: Comamonas testosteroni and Acidovorax
      sp. can remove acrylonitrile completely up to 1904.8 mg/L within 66.6 h and
      1538.5 mg/L within 143.3 h, respectively. Comamonas testosteroni degraded
      acrylonitrile faster than Acidovorax sp., and accumulated much more acrylic acid
      in the medium than Acidovorax sp. The addition of acrylamide to the medium was
      removed by Comamonas testosteroni and Acidovorax sp. Both strains utilized
      acrylic acid, a metabolic by-product of acrylonitrile, as a carbon source and
      ammonium nitrogen, a metabolic by-product of acrylonitrile, as a nitrogen source
      for growth. Comamonas testosteroni and Acidovorax sp. removed propionitrile
      completely up to 1352.8 mg/L and 975.7 mg/L within 166.9 h, respectively. With
      isobutyronitrile as a substrate, more than 97.8% could be removed within 169.8 h
      by Comamonas testosteroni up to 1352.8 mg/L, and by Acidovorax sp. up to 975.7
      mg/L. These two strains could remove allyl cyanide completely up to 775 mg/L
      within 49.1 h and benzonitrile completely up to 442.7 mg/L within 31.1 h. Because
      Comamonas testosteroni and Acidovorax sp. have good degrading ability for
      removing nitrile compounds they are expected to play an important role in the
      treatment of nitrile compounds.

PMID- 15242126
TI  - Promoting nitrification by using functional gel as immobilizing medium under
      different temperature stimulation patterns.
AB  - Nitrification with nitrifiers immobilized by temperature stimuli-responsive N
      isopropylacrylamide-Chlorophyll (NIPA-CH) gel was investigated under several
      patterns of temperature stimulation, compared with that at constant temperature.
      The results show that in response to a cyclic temperature stimulus of 32-36
      degrees C or 32-34 degrees C with a period of 4 or 2 h, respectively, the gel
      swelled and shrank reversibly and promoted biological nitrification. But in the
      case of a cyclic temperature change of 32-36 degrees C with a stimulation cycle
      of 2 h, nitrite oxidization declined. The results suggested that adequate
      stimulus facilitated substrate transfer into gels that promoted nitrification in
      the reactor, but quite frequent swelling and shrinking of the gel squeezed
      nitrifier out of the gel resulting in washing nitrifier out and declining
      nitrification. When gels that undergone cyclic temperature stimuli began to swell
      at 32 degrees C, oxygen consumption of nitrifiers in the gels was more than that
      of nitrifiers in the gels at constant temperature of 32 degrees C all the time,
      but when gels of two reactors shrank at 36 degrees C, their oxygen consumption
      reduced and there was almost no difference between them regardless of their
      undergone temperature stimuli once or not. Practical application of nitrifier
      immobilized by NIPA-CH gel in wastewater treatment was also discussed.

PMID- 15242127
TI  - Effect of Alcaligenes faecalis on nitrous oxide emission and nitrogen removal in
      three phase fluidized bed process.
AB  - Nitrous oxide (N2O), one of the greenhouse effect gases, has not been known that
      how much N2O is produced from municipal wastewater treatment and what its
      management should be. In this study, for controlling nitrous oxide emission and
      removing nitrogen from municipal wastewater, we experimented the three phase
      fluidized bed process equipped with draft tube along with immobilized Alcaligenes
      faecalis, a typical heterotrophic nitrifer and a predominant genus. Also we
      evaluated the optimum treatment condition of the three phase fluidized bed
      process for emitting nitrous oxide. The results of this study showed that the
      three phase fluidized bed process was more effective than the activated sludge
      process for controlling nitrous oxide emission and removing nitrogen. Increasing
      amount of A. faecalis in reactor should be encouraged for controlling nitrous
      oxide emission and removing nitrogen. In addition, the activated sludge process
      using immobilized A. faecalis as a carrier had more nitrogen removal efficiency
      than conventional activated sludge process. The accumulation of NO2-N, NO3-N
      resulted in high N2O emission. Therefore, we suggested that it is necessary to
      reduce NO2-N and NO3-N for both reducing N2O emission and improving nitrogen
      removal.

PMID- 15242128
TI  - Comparative analysis of vertical heterogeneity of microbial community in sulfur
      packed reactor used for autotrophic nitrate removal.
AB  - To better understand microbial community in sulfur-based nitrate removal process,
      comparative molecular analyses were performed with the biofilm formed on sulfur
      particles that were obtained from different bed-heights of a laboratory-scale
      reactor employed for the process. Microbial community in the reactor showed
      vertical heterogeneity in terms of total cell count and nitrate removal activity.
      DAPI (4',6-diamidino-2-phenylindole) staining revealed that total cell count (per
      g sulfur particle) gradually decreased as bed height increased until reaching
      approximately middle of the reactor bed, showing a nearly plateau afterward. This
      result partly supported ion chromatography result that most nitrate removal
      activity was found in the lower part of the reactor bed. Phylogenetic composition
      of bacterial community in the biofilm was almost similar regardless of bed height
      as determined by whole cell hybridization using group-specific probes. Cells
      affiliated with the beta- and gamma-Proteobacteria were the most abundant
      proteobacterial groups throughout the bed, although their fractions were
      fluctuating along the bed height. Total number of the two major groups decreased
      as bed height increased, showing similar trend to total cell count and nitrate
      removal activity. Denaturating gradient gel electrophoresis revealed similar
      profiles of nitrous oxide reductase gene (nosZ) fragments from denitrifying
      populations at the different bed-heights, suggesting similar diversity of the
      nosZ fragments regardless of bed height.

PMID- 15242129
TI  - Feasibility analysis of in-plant control for water minimization and wastewater
      reuse in a wool finishing textile mill.
AB  - This study evaluates the feasibility of water minimization and wastewater reuse
      for a wool finishing textile mill. The evaluation process is based upon a
      detailed analysis on water use, process profile and wastewater characterization,
      indicating a potential for 34% reduction in water consumption and for 23% of
      wastewater recovery for reuse. Wastewater reuse requires treatment and results in
      a remaining wastewater stream with stronger character and consequently more
      costly to treat. The feasibility includes technical considerations for
      appropriate treatment alternatives and related cost factors for water
      consumption, treatment for reuse and for discharge either to sewer or to
      receiving media.

PMID- 15242130
TI  - Estimating nitrogen and phosphorus contents using model integrated in small
      agricultural watersheds.
AB  - The Agricultural Nonpoint Source Pollution Model (AGNPS) was applied to estimate
      the loads of nitrogen and phosphorus according to antecedent soil moisture
      conditions (AMC) using probable rainfall in a stream draining small agricultural
      watersheds. Calibration and verification of the model were performed using
      observed data collected from rainfall events in the Imgo watersheds during 1997
      1998. Evaluation of model outputs was based on graphical displays contrasting
      observed and simulated values for each rainfall-runoff event, and standard
      statistics such as coefficient of efficiency. The coefficient of efficiency of
      peak flow, total N, and total P in the estimation were 0.97, 0.93, and 0.74,
      respectively. Probable rainfall of Imgo watersheds was computed for several
      return periods using the frequency analysis of Gumbel's extreme value
      distribution. As the probable flood increase, concentrations of total N and total
      P generally decrease. Loss of N and P was proportional to the preceding soil
      water content in the same probable rainfall. The excessive fertilization under
      AMC-III condition can cause relatively higher outflow of N and P from the soil.
      It can be concluded that surface runoff and sediment transport influence soil
      quality and the quality of water absorption and AGNPS can provide realistic
      estimates of nonpoint source nutrient yields.

PMID- 15242131
TI  - Attachment characteristics of biofilms in fixed-lock media for swine wastewater
      treatment.
AB  - A correlation between equilibrium biofilm thickness and biomass density in a
      laboratory-scale submerged media aeration system was evaluated. The system had
      lock-type media, and swine wastewater was used as a substrate. The influent
      wastewater had chemical oxygen demand and biochemical oxygen demand
      concentrations of 2940-3800 and 1310-1730 mg/L, respectively. The hydraulic
      retention time of the system was varied from 0.5 to 2 days. The following
      conclusions can be drawn from the operational results: (i) the maximum biofilm
      density was observed when the equilibrium biofilm thickness was 180-200 microm,
      (ii) the activated biomass represented as volatile suspended solids per unit area
      decreased after 10 days of operation, and (iii) the removal rate of chemical
      oxygen demand increased rapidly up for an equilibrium biofilm thickness up to 200
      microm, but no further increase was observed for thicknesses of 200-1200 microm.

PMID- 15242132
TI  - Removal of residual COD in biologically treated paper-mill effluent and
      degradation of lignin using nonthermal plasma unit.
AB  - This manuscript focused on the degradation behavior of lignin and the reduction
      of residual COD in the biologically treated paper-mill effluent by means of
      ionized gas from nonthermal plasma unit. The removal efficiencies of COD, lignin,
      and color after treated with ionized gas were over 95, 93, and 97%, respectively.
      It has been found that the degradation of aromatic ring has been proved by FTIR,
      1H NMR and UV spectra. The degradation of lignin through ionized gas was
      accompanied with the increase of SO4(2-) and the decrease in pH. The results show
      that the residual COD in the biologically treated paper-mill effluent contains
      NBD matter with aromatic ring compounds. Also NBD organic matter such as aromatic
      ring in effluent treated with ionized gas was degraded. The residual COD declined
      by 60% at the ionized gas flow rate 5 L/min and HRT 30 min.

PMID- 15242133
TI  - Removal of ammonium from tannery wastewater by electrochemical treatment.
AB  - The removal of ammonium from coagulated tannery wastewaters was investigated by
      an electrochemical method using Ti/IrO2 as an anode. Operating variables
      including the current density, pH and chloride concentration were considered in
      order to determine their effect on the ammonium removal efficiency. A maximum
      ammonium removal rate of 78.9% was achieved after 30 min of electrochemical
      treatment with 4 A dm(-2) of current density. During the electrolysis, it had
      been observed that the ammonium removal was accompanied with an elimination of
      the organics. Generation of hydroxyl radical was identified during the experiment
      with hydroxyl radical probe compound of pCBA. Chloride ion worked as the
      scavenger of hydroxyl radical. Role of free chlorine was the main oxidant for the
      elimination of ammonium and organic substances. As a result, the biodegradability
      of tannery wastewater increased after electrochemical treatment. The energy
      consumed per 1 kg of ammonium removal was 26.6 kWh for initial NH4-N
      concentration of 870 mg L(-1).

PMID- 15242134
TI  - Treatment of tannery wastewater with high nitrogen content using anoxic/oxic
      membrane bio-reactor (MBR).
AB  - Bench scale membrane bio-reactors were operated to investigate the treatment
      efficiency of tannery wastewater with high organic and nitrogen contents and the
      optimum operating conditions were derived. The optimum ratio of the volume of
      anoxic denitrification tank to aerobic nitrification tank was 50% when
      denitification/nitrication MBR process was used to treat tannery wastewater. It
      was also found that supplementation of phosphorus to maintain COD:T-P ratio of
      100:1 was needed to achieve the best performance. Under these conditions, the
      effluent COD and T-N were 160 and 54 mg/L, respectively which satisfied the
      effluent limits for the tannery wastewater.

PMID- 15242135
TI  - Performance of magnesium ammonium phosphate precipitation and its effect on
      biological treatability of leather tanning industry wastewaters.
AB  - Leather tanning industry is one of the several industries discharging significant
      amount of nitrogen. Magnesium ammonium phosphate (MAP) precipitation is a
      promising pretreatment for leather tanning industry wastewaters for the control
      of toxic parameters; excess suspended solids as well as nitrogen which increase
      the cost and complexity of following biological treatment. Application of MAP
      precipitation, however, modifies the characteristics and biological treatability
      of wastewaters. In this study, characteristics and biological treatability of MAP
      precipitation effluent were experimentally investigated using the wastewaters
      obtained from a bovine leather processing plant. An experimental study involving
      the determination of COD fractions and kinetic parameters of biological treatment
      was conducted for both gravity settling and MAP precipitation. Results of the
      study indicated that MAP precipitation, in addition to high degree of nitrogen
      removal, yielded a soluble, readily biodegradable effluent which was also free
      from toxics. MAP precipitation provided an effluent COD of almost half of that of
      gravity settling. Reduced value of soluble residual microbial products (Sp)
      obtained with MAP precipitation effluent was an additional benefit.

PMID- 15242136
TI  - Development of biological livestock wastewater treatment system combined with
      physical pretreatment and chemical posttreatment.
AB  - Lab-scale livestock wastewater treatment process was operated. Treatment process
      was composed of anaerobic reactor, aerobic reactor, anoxic reactor, settler, and
      microorganisms activation reactor. We divided this system into Systems 1-5
      according to various conditions. In Systems 4 and 5, ammonia stripping was
      performed as pretreatment. And flocculation was performed as posttreatment.
      Average influent concentrations of COD, BOD, TKN, and TP were 21,894, 11,533,
      2255, and 415 mg/L, respectively, and COD/N and BOD/N ratios in influent were 9.9
      and 5.3, respectively. When ammonia stripping was performed as pretreatment,
      effluent BOD concentration was 44.4 mg/L and removal efficiency was 99.62%. TN
      removal efficiencies in Systems 4 and 5 were 84.1 and 95.2%, respectively, and
      effluent TN concentrations were 305.9 and 78.4 mg/L, respectively, which was
      because of with without pH control. In operation period of Systems 4 and 5,
      average SNR and SDNR were 18.6 and 17.4 g N/kg MLSS/d, respectively, which was
      rate as much as endogenous denitrification rate because of long SRT due to low
      F/M ratio. In Systems 3, 4, and 5, optimal doses of flocculation agent were 350,
      100, and 100 mg Fe/L. This difference was caused by alkalinities of Systems 3, 4,
      and 5, which were 750, 284, and 162 mg/L as CaCO3.

PMID- 15242137
TI  - Appropriate design of activated sludge systems for nitrogen removal from high
      strength wastewaters.
AB  - The study is focused on defining a conceptual approach for the design of
      activated sludge systems treating strong wastewater for nitrogen removal. The
      effect of major factors such as COD/N ratio, denitrification potential, available
      nitrate, anoxic volume fraction, and recycle ratio is evaluated in terms of basic
      stoichiometry. An algorithm for appropriate design is developed for a continuous
      flow activated sludge and sequencing batch reactor, both operated in a pre
      denitrification mode. The design approach is tested for two types of strong
      industrial wastewaters with different N contents and COD/N ratios and a typical
      domestic sewage for comparative evaluation.

PMID- 15242138
TI  - Public awareness about depression: the effectiveness of a patient guideline.
AB  - OBJECTIVE: To evaluate the effectiveness of a patient guideline for educating the
      public in the recognition and treatment of depression. METHOD: Lay subjects were
      interviewed regarding their knowledge and beliefs about depression through the
      use of a semi-structured questionnaire. They were asked to "think aloud" while
      evaluating two clinical scenarios about depression, both with and without the use
      of a patient guideline. All interviews were audio taped, transcribed, and
      analyzed for subjects' thought processes and accuracy of responses in the
      presence and absence of the guideline. RESULTS: Subjects with no prior history of
      depression identified fewer symptoms of depression listed in the patient
      guideline than did subjects with a history of depression. In the absence of the
      guideline, only 50% and 38% of subjects provided accurate diagnosis of depression
      for the simple and complex problems respectively. In the presence of the
      guideline, 92% and 83% of subjects provided an accurate diagnosis of depression
      for the simple and complex problems respectively. CONCLUSIONS: Lay people have a
      limited knowledge of depression and its treatment, and are less able to recognize
      symptoms of depression without the help of patient guideline. The guideline
      primes lay people to better recognize these symptoms and their relationship to
      diagnosis. This level of understanding about depression by lay people will
      facilitate improved communication between physicians and their patients.

PMID- 15242139
TI  - Prevalence and determinants of depressive disorders in primary care practice in
      Spain.
AB  - OBJECTIVE: Depressive disorders are considered to be a public health problem.
      Primary health care plays an important role in the treatment of such disorders.
      Our aim is to determine the prevalence and determinant factors of major
      depression and dysthymia in consecutive primary care attenders. METHOD: The study
      took place in medical consultations in 10 Primary Care Centers in Tarragona
      (Spain). It was designed as a two-phase cross-sectional study. In the first phase
      we screened 906 consecutive patients according to Zung's Self-Rating Depression
      Scale. In the second phase the 209 patients whose results were positive and 97
      patients whose results were negative (1/7 chosen at random) were given the
      Structured Clinical Interview for DSM-IV Axis I Disorders, plus a series of
      questionnaires. We evaluated the link between major depression and dysthymia and
      several sociodemographic and clinical variables using non-conditional logistic
      regression. RESULTS: Weighted prevalence was 14.3% (CI 95%: 11.2-17.4) for major
      depression and 4.8% (CI 95%: 2.8-6.8) for dysthymia. Independently linked to the
      presence of major depression were female sex, panic disorder, generalized anxiety
      disorder, frequency of primary care visits, and clinical presentation in the form
      of explicitly psychosocial symptoms as opposed to exclusively somatic symptoms.
      Independently linked to the presence of dysthymia were age, generalized anxiety
      disorder and psychosocial symptoms. CONCLUSION: In our area, depressive disorders
      in primary care attenders are very common. General practitioners should be aware
      of this fact so that these disorders can be detected and treated correctly.

PMID- 15242140
TI  - The 13- and 20-item Hopkins Symptom Checklist Depression Scale: psychometric
      properties in primary care patients with minor depression or dysthymia.
AB  - OBJECTIVE: Depression scales that are responsive to changes in clinical symptoms
      are important for clinical monitoring and outcomes assessment in longitudinal
      studies. We evaluated the psychometric properties and responsiveness to clinical
      change of the 13- and 20-item versions of the Hopkins Symptom Checklist
      Depression Scale (HSCL-D). METHODS: A secondary data analysis from a large 11
      week, multicenter clinical trial, comparing three treatments was performed. Adult
      patients with minor depression or dysthymia and a score of > or = 10 on the
      Hamilton Depression Rating Scale (HDRS) were recruited from primary care clinics.
      Item-total correlations and Cronbach alphas were computed for HSCL-D-13 and HSCL
      D-20. Clinical response at 11 weeks was defined by a Hamilton Depression Rating
      Scale (HDRS) < 10, clinical remission by a HDRS < 7, and criterion symptom
      remission by < or = 1 DSM-III-R criterion symptoms. Standardized effect sizes and
      Guyatt's responsiveness statistic were determined for the 13- and 20-item HSCL-D.
      RESULTS: Of the 656 subjects enrolled, 511 (77.9%) had complete data and were
      included in the analysis. Patients were 61.1 +/- 15.0 years old; minor depression
      was diagnosed in 238, dysthymia in 273. Both scales had good internal
      consistency; Cronbach's alpha = 0.835 and 0.859 for the 13- and 20-items
      questionnaires respectively. Standardized effect sizes for clinical response
      (0.62 for the HSCL-D-13; 0.66 for the HSCL-D-20), clinical remission (0.69 and
      0.70), and criterion symptom remission (0.65 and 0.67) showed moderate to large
      effects and did not differ significantly for the two versions. Responsiveness was
      virtually identical for patients with minor depression and dysthymia but
      responsiveness was substantially lower for ethnic minorities. CONCLUSION: The
      HSCL-D-13 and 20-item versions have similar responsiveness to change. For use in
      European Americans, we recommend the HSCL-D-13 if response burden is the
      preeminent consideration. To more fully capture DSM criterion symptoms, we
      recommend the HSCL-D-20.

PMID- 15242141
TI  - Child psychiatric disorders in a primary care Arab population.
AB  - OBJECTIVES: Physical and psychiatric comorbidity is relatively common in general
      practice but there have been few systematic studies using clinical interviews of
      children attending the primary care services in the Arab population, and none
      from the Gulf countries. This study was undertaken to determine the prevalence
      and nature of child psychiatric morbidity in primary care in the United Arab
      Emirates (UAE). METHOD: Systematic psychiatric evaluations were carried out on
      consecutive children aged 6 to 18 years visiting their primary care doctors in Al
      Ain. The sample consisted of 141 (50.7%) boys and 137 (49.3%) girls. RESULTS:
      Forty-three percent of the 278 children received a DSM-IV diagnosis. Of these, 46
      (38%) were males and 74 (62%) were females. However, only 1.1% (3/120) of the
      patients consulted general practitioners for a primary psychiatric symptom. The
      most common diagnosis was anxiety disorder followed by depression. Obsessive
      compulsive disorder was present in 11%, conduct disorder in 7%, and attention
      deficit hyperactivity disorder in 3% of those with a diagnosis. A statistically
      significant association was found between DSM-IV caseness and female gender,
      higher number of children in the household, relationship problems in the family,
      physical illness and family history of psychiatric disorder. Other factors that
      did not show any significant association were age, nationality, socioeconomic
      status, parental education or occupation, scholastic performance or developmental
      delay in the child, or parental consanguinity. CONCLUSION: Our findings suggest
      that psychiatric disorders are common among young people of Arab origin attending
      primary care facilities, and that doctors need to be vigilant about this
      possibility.

PMID- 15242142
TI  - Religiosity may help preserve the cortisol rhythm in women with stress-related
      illness.
AB  - OBJECTIVE: Fibromyalgia has been characterized as a basic disorder of endocrine
      stress responses in which psychological stress has been linked both with etiology
      and symptom severity. This study investigated associations of religiosity and
      spirituality with psychological and physiological (endocrine) measures of stress
      in a sample of women with fibromyalgia. METHOD: Ninety-one participants provided
      self-reports of religiosity and spirituality using the Duke University Religion
      Index (DUREL) and the Index of Core Spiritual Experiences (INSPIRIT).
      Psychological outcomes were measured with the Perceived Stress Scale (PSS), and
      diurnal salivary cortisol profiles were measured as an indicator of
      neuroendocrine regulation. RESULTS: Hierarchal regression analyses controlling
      for age and medications likely to affect cortisol levels revealed significant
      associations of nonorganizational religiosity and intrinsic religiosity with the
      diurnal cortisol rhythm. Patients reporting medium or high religiosity had
      rhythmic cortisol profiles characterized by high morning and low evening levels.
      In contrast, cortisol rhythms of those reporting low religiosity appeared
      flattened. The association between intrinsic religiosity and cortisol rhythm
      persisted after controlling for social support. No significant effects of
      religiosity or spirituality on perceived stress were observed. CONCLUSIONS: These
      data suggest that religiosity may have a protective effect on the physiological
      effects of stress among women with fibromyalgia.

PMID- 15242143
TI  - Orange juice-induced hyperkalemia in schizophrenia.
AB  - Some fruit juices have very high potassium content. However, only several cases
      of juice-induced hyperkalemia have been reported that involved non-psychiatric,
      diabetic outpatients with renal compromise. We present a highly unusual case of a
      66-year-old non-diabetic, schizophrenic woman with psychogenic polydipsia and
      normal renal function who developed hyperkalemia secondary to excessive orange
      juice consumption while an inpatient. In addition to demonstrating this
      previously undescribed medical comorbidity of schizophrenia, this case highlights
      the need for careful attention when communicating with both nursing and patients
      when managing psychogenic polydipsia.

PMID- 15242145
TI  - Pellagra encephalopathy following B-complex vitamin treatment without niacin.
AB  - Pellagra is caused by nicotinic acid deficiency; it is rarely encountered in
      developed countries, and it is mainly related to poverty and malnutrition, as
      well as with chronic alcoholism. We report the case of an alcoholic patient who
      was diagnosed with pellagra and administered B-complex vitamin tablets that did
      not contain niacin. A few weeks later, the patient developed nervousness,
      irritability, insomnia and, consequently, delusional ideas and hallucinations,
      for which he had to be hospitalized. After his admission, the patient manifested
      loss of consciousness and myoclonus. All of his symptoms (cutaneous,
      neurological, and psychiatric) resolved fully with treatment with niacin in
      combination with other B-complex vitamins. All undiagnosed encephalopathies in
      alcoholic patients should be treated with multiple vitamin therapy, including
      nicotinic acid.

PMID- 15242144
TI  - Management of marked liver enzyme increase during clozapine treatment: a case
      report and review of the literature.
AB  - OBJECTIVE: Clozapine-induced hepatotoxicity is not infrequent and usually
      transient. It mostly causes asymptomatic elevation of liver transaminases.
      "Elevation in liver enzymes to what extent should preclude further treatment?" or
      "Is only a dose-reduction sufficient?" are questions yet to be answered. The
      present article uses a case report to discuss the treatment alternatives when
      liver enzymes reach three times the upper normal limits during the clozapine
      therapy. METHODS: In the following case report, the authors describe a 27-year
      old male patient diagnosed with schizophrenia, resistant to different atypical
      and typical antipsychotics. Based on the pathological findings of our patient and
      a review of the literature, the author summarizes the reasons for the liver
      enzymes increase and treatment alternatives during clozapine treatment. RESULTS:
      Substantial improvement was achieved with clozapine therapy. Increase in liver
      enzymes at the beginning of the clozapine treatment was successfully managed with
      a multidisciplinary approach: the treatment was initially withdrawn, afterwards
      restarted, and carefully continued. CONCLUSION: The authors demonstrate that
      clozapine may be cautiously continued in selected patients who showed marked
      psychiatric improvement with clozapine in the face of liver enzyme elevation.

PMID- 15242146
TI  - A case of factitious disorder involving menstrual blood smeared on the face.
AB  - This article presents a case of factitious disorder in which a female smeared
      menstrual blood on her face. The patient was admitted to our otolaryngology
      clinic complaining of bleeding from the mouth, nose, ears and eyes. This event
      reportedly occurred three to four times on a daily basis. She acknowledged nine
      prior admissions to different specialists over the last two years. Following
      psychiatric consultation, we diagnosed factitious disorder with predominantly
      physical signs and symptoms. She was started on Fluoxetine 20 mg/day and
      supportive interviews were organized. After diagnosis, we observed that her
      symptoms decreased over two months. The symptoms did not reoccur three to nine
      months after treatment. This case report outlines two important features. The
      first is that a case of this type has not been reported before, and the second
      feature is that this case demonstrates the effect of cultural factors greatly
      different from those seen in classical factitious disorder.

PMID- 15242147
TI  - Megacities and atmospheric pollution.
AB  - About half of the world's population now lives in urban areas because of the
      opportunity for a better quality of life. Many of these urban centers are
      expanding rapidly, leading to the growth of megacities, which are defined as
      metropolitan areas with populations exceeding 10 million inhabitants. These
      concentrations of people and activity are exerting increasing stress on the
      natural environment, with impacts at urban, regional and global levels. In recent
      decades, air pollution has become one of the most important problems of
      megacities. Initially, the main air pollutants of concern were sulfur compounds,
      which were generated mostly by burning coal. Today, photochemical smog--induced
      primarily from traffic, but also from industrial activities, power generation,
      and solvents--has become the main source of concern for air quality, while sulfur
      is still a major problem in many cities of the developing world. Air pollution
      has serious impacts on public health, causes urban and regional haze, and has the
      potential to contribute significantly to climate change. Yet, with appropriate
      planning, megacities can efficiently address their air quality problems through
      measures such as application of new emission control technologies and development
      of mass transit systems. This review is focused on nine urban centers, chosen as
      case studies to assess air quality from distinct perspectives: from cities in the
      industrialized nations to cities in the developing world. While each city--its
      problems, resources, and outlook--is unique, the need for a holistic approach to
      the complex environmental problems is the same. There is no single strategy in
      reducing air pollution in megacities; a mix of policy measures will be needed to
      improve air quality. Experience shows that strong political will coupled with
      public dialog is essential to effectively implement the regulations required to
      address air quality problems.

PMID- 15242148
TI  - Ozone and other air quality-related variables affecting visibility in the
      southeast United States.
AB  - An analysis of ozone (O3) concentrations and several other air quality-related
      variables was performed to elucidate their relationship with visibility at five
      urban and semi-urban locations in the southeast United States during the summer
      seasons of 1980-1996. The role and impact of O3 on aerosols was investigated to
      ascertain a relationship with visibility. Regional trend analysis over the 1980s
      reveals an increase in maximum O3 concentration coupled with a decrease in
      visibility. However, a similar analysis for the 1990s shows a leveling-off of
      both O3 and visibility; in both cases, the results were not statistically
      significant at the 5% level. A case study of site-specific trends at Nashville,
      TN, followed similar trends. To better understand the relationships between O3
      concentration and visibility, the analysis was varied from yearly through daily
      to hourly averaged values. This increased temporal resolution showed a
      statistically significant inverse relationship between visibility and O3. Site
      specific hourly r2 values ranged from 0.02 to 0.43. Additionally, by performing
      back-trajectory analysis, it was found that the visibility degraded by air mass
      migration over polluted areas.

PMID- 15242149
TI  - Determination of levoglucosan in atmospheric fine particulate matter.
AB  - A microanalytical method suitable for the quantitative determination of the sugar
      anhydride levoglucosan in low-volume samples of atmospheric fine particulate
      matter (PM) has been developed and validated. The method incorporates two sugar
      anhydrides as quality control standards. The recovery standard sedoheptulosan
      (2,7-anhydro-beta-D-altro-heptulopyranose) in 20 microL solvent is added onto
      samples of the atmospheric fine PM and aged for 1 hr before ultrasonic extraction
      with ethylacetate/ triethylamine. The extract is reduced in volume, an internal
      standard is added (1,5-anhydro-D-mannitol), and a portion of the extract is
      derivatized with 10% by volume N-trimethylsilylimidazole. The derivatized extract
      is analyzed by gas chromatography/mass spectrometry (GC/MS). The recovery of
      levoglucosan using this procedure was 69 +/- 6% from five filters amended with 2
      microg levoglucosan, and the reproducibility of the assay is 9%. The limit of
      detection is approximately 0.1 microg/mL, which is equivalent to approximately
      3.5 ng/m3 for a 10 L/min sampler or approximately 8.7 ng/m3 for a 4 L/min
      personal sampler (assuming 24-hr integrated samples). We demonstrated that
      levoglucosan concentrations in collocated samples (expressed as ng/m3) were
      identical irrespective of whether samples were collected by PM with aerodynamic
      diameter < or = 2.5 microm or PM with aerodynamic diameter < or = 10 microm
      impactors. It was also demonstrated that X-ray fluorescence analysis of samples
      of atmospheric PM, before levoglucosan determinations, did not alter the levels
      of levoglucosan.

PMID- 15242150
TI  - Simulating urban-scale air pollutants and their predicting capabilities over the
      Seoul metropolitan area.
AB  - Urban-scale air pollutants for sulfur dioxide, nitrogen dioxide, particulate
      matter with aerodynamic diameter > or = 10 microm, and ozone (O3) were simulated
      over the Seoul metropolitan area, Korea, during the period of July 2-11, 2002,
      and their predicting capabilities were discussed. The Air Pollution Model (TAPM)
      and the highly disaggregated anthropogenic and the biogenic gridded emissions (1
      km x 1 km) recently prepared by the Korean Ministry of Environment were applied.
      Wind fields with observational nudging in the prognostic meteorological model
      TAPM are optionally adopted to comparatively examine the meteorological impact on
      the prediction capabilities of urban-scale air pollutants. The result shows that
      the simulated concentrations of secondary air pollutant largely agree with
      observed levels with an index of agreement (IOA) of >0.6, whereas IOAs of
      approximately 0.4 are found for most primary pollutants in the major cities,
      reflecting the quality of emission data in the urban area. The observationally
      nudged wind fields with higher IOAs have little effect on the prediction for both
      primary and secondary air pollutants, implying that the detailed wind field does
      not consistently improve the urban air pollution model performance if emissions
      are not well specified. However, the robust highest concentrations are better
      described toward observations by imposing observational nudging, suggesting the
      importance of wind fields for the predictions of extreme concentrations such as
      robust highest concentrations, maximum levels, and >90th percentiles of
      concentrations for both primary and secondary urban-scale air pollutants.

PMID- 15242151
TI  - On-road vehicle particulate matter and gaseous emission distributions in Las
      Vegas, Nevada, compared with other areas.
AB  - During the spring and summer of 2000, 2001, and 2002, gaseous and particulate
      matter (PM) fuel-based emission factors for approximately 150,000 low-tailpipe,
      individual vehicles in the Las Vegas, NV, area were measured via on-road remote
      sensing. For the gaseous pollutants (carbon monoxide, hydrocarbons, and nitrogen
      oxide), a commercial vehicle emissions remote sensing system (VERSS) was used.
      The PM emissions were determined using a Lidar-based VERSS. Emission
      distributions and their shapes were analyzed and compared with previous studies.
      The large skewness of the distributions is evident for both gaseous pollutants
      and PM and has important implications for emission reduction policies, because
      the majority of emissions are attributed to a small fraction of vehicles. Results
      of this Las Vegas study and studies at other geographical locations were
      compared. The gaseous pollutants were found to be close to those measured by
      VERSS in other U.S. cities. The PM emission factors for spark ignition and diesel
      vehicles are in the range of previous tunnel and dynamometer studies.

PMID- 15242152
TI  - Catalytic destruction of dichloromethane using perovskite-type oxide catalysts.
AB  - Dichloromethane (DCM, also known as methylene chloride [CH2Cl2]) is often present
      in industrial waste gas and is a valuable chemical product in the chemical
      industry. This study addresses the oxidation of airstreams that contain CH2Cl2 by
      catalytic oxidation in a tubular fixed-bed reactor over perovskite-type oxide
      catalysts. This work also considers how the concentration of influent CH2Cl2 (Co
      = 500-1000 ppm), the space velocity (GHSV = 5000-48,000 1/hr), the relative
      humidity (RH = 10-70%) and the concentration of oxygen (O2 = 5-21%) influence the
      operational stability and capacity for the removal of CH2Cl2. The surface area of
      lanthanum (La)-cobalt (Co) composite catalyst was the greatest of the five
      perovskite-type catalysts prepared in various composites of La, strontium, and Co
      metal oxides. Approximately 99.5% CH2Cl2 reduction was achieved by the catalytic
      oxidation over LaCoO3-based perovskite catalyst at 600 degrees C. Furthermore,
      the effect of the initial concentration and reaction temperature on the removal
      of CH2Cl2 in the gaseous phase was also monitored. This study also provides
      information that a higher humidity corresponds to a lower conversion. Carbon
      dioxide and hydrogen chloride were the two main products of the oxidation process
      at a relative humidity of 70%.

PMID- 15242153
TI  - Supply curves for using powder river basin coal to reduce sulfur emissions.
AB  - Supply curves were prepared for coal-fired power plants in the contiguous United
      States switching to Wyoming's Powder River Basin (PRB) low-sulfur coal. Up to 625
      plants, representing approximately 44% of the nameplate capacity of all coal
      fired plants, could switch. If all switched, more than dollars 8.8 billion
      additional capital would be required and the cost of electricity would increase
      by up to dollars 5.9 billion per year, depending on levels of plant derating.
      Coal switching would result in sulfur dioxide (SO2) emissions reduction of 4.5
      million t/yr. Increase in cost of electricity would be in the range of 0.31-0.73
      cents per kilowatt-hour. Average cost of S emissions reduction could be as high
      as dollars 1298 per t of SO2. Up to 367 plants, or 59% of selected plants with
      32% of 44% nameplate capacity, could have marginal cost in excess of dollars 1000
      per t of SO2. Up to 73 plants would appear to benefit from both a lowering of the
      annual cost and a lowering of SO2 emissions by switching to the PRB coal.

PMID- 15242154
TI  - Emissions of sulfur trioxide from coal-fired power plants.
AB  - Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid
      deposition. Consequently, these emissions need to be low enough to not cause
      opacity violations and acid deposition. Generally, a small fraction of sulfur (S)
      in coal is converted to SO3 in coal-fired combustion devices such as electric
      utility boilers. The emissions of SO3 from such a boiler depend on coal S
      content, combustion conditions, flue gas characteristics, and air pollution
      devices being used. It is well known that the catalyst used in the selective
      catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small
      fraction of sulfur dioxide in the flue gas to SO3. The extent of this oxidation
      depends on the catalyst formulation and SCR operating conditions. Gas-phase SO3
      and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and
      wet scrubber), result in fine acidic mist, which can cause increased plume
      opacity and undesirable emissions. Recently, such effects have been observed at
      plants firing high-S coal and equipped with SCR systems and wet scrubbers. This
      paper investigates the factors that affect acidic mist production in coal-fired
      electric utility boilers and discusses approaches for mitigating emission of this
      mist.

PMID- 15242155
TI  - Is globalization undermining the welfare state? The evolution of the welfare
      state in developed capitalist countries during the 1990s.
AB  - The authors analyze the evolution of macro-indicators of social and economic well
      being during the 1990s in the majority of developed capitalist countries, grouped
      according to their dominant political traditions since the end of World War II.
      Their analysis shows that, despite the economic globalization of commerce and
      finance, "politics still matters" in explaining the evolution of the welfare
      states and labor markets in these countries; the impact of the globalization of
      financial capital in forcing reductions in the financial resources available for
      welfare state purposes has been exaggerated.

PMID- 15242156
TI  - Is the Canadian health care system fiscally sustainable?
AB  - Current concerns over escalating health care costs and the sustainability of the
      Canadian health care system are based on analytical concepts and models that have
      their own limitations and deficiencies. Measuring health care costs across
      subsectors over the long-term period, the authors argue that Canada's health care
      costs, especially those under the direct control of provincial governments, are
      relatively stable. Using appropriate measures of sustainability, there is no
      indication that Canada's public health care expenditure is unsustainable. Nor is
      there any indication that Canada's public health care expenditures are out of
      line with those of its main trading competitors, including the United States.

PMID- 15242157
TI  - Health care or health trade? A historic moment of choice.
AB  - During the 20th century, medical care evolved from a notional economy of trying
      to a real economy of doing. Care systems can therefore usefully be measured and
      evaluated as production systems. Whether they will succumb to the pattern of
      competitive commodity production for profit in the market, or will succeed in
      developing their own new gift economy for human needs, will become a dominant
      political and economic issue in the 21st century. Health care is now becoming
      industrialized in essentially the same way as textile manufacture was
      industrialized in the 19th century, with corresponding loss of control by skilled
      workers over their work processes. The outcome of the struggle between skilled
      handloom weavers and their industrializing employers was determined by the huge
      rise in productivity associated with machines. The outcome of current struggles
      between public service and state-subsidized corporate care for profit will be
      decided likewise by superior productivity. Evidence suggests that in terms of
      health outcome, democratized public care with a much expanded and diversified
      workforce could be far more productive than industrialization.

PMID- 15242158
TI  - Unhealthy European health policy.
AB  - The European Union claims that the defense of its welfare state is one of today's
      most important challenges. This article analyzes whether the European governments
      and the European Union really pursue a policy that strengthens their health and
      social security systems, or one that is in itself a threat to health and social
      security. After a summary of the origin and evolution of the European health
      systems, the authors pinpoint underlying reasons for reform and demonstrate how,
      since the 1990s, the European Union has built a strict financial and political
      straitjacket, forcing these systems to carry out privatization and cutbacks.
      Reform measures can be divided into three interdependent categories: (1) the
      increasing influence of governments on health care organization, to enable
      restructuring; (2) measures aimed at reducing public expenses, including higher
      financial contributions by patients and restrictions on the range of services
      provided; and (3) measures that establish competition and hidden or open
      privatization of services and insurance systems. Through these mechanisms public
      expenses are reduced while private health care expenses (and private profits)
      rise freely. Ongoing European health care reforms thus struggle with the
      contradictions between responding to growing collective needs and securing or
      increasing private profits.

PMID- 15242159
TI  - Wounding the messenger: the new economy makes occupational health indicators too
      good to be true.
AB  - The U.S. Bureau of Labor Statistics and workers' compensation insurers reported
      dramatic drops in rates of occupational injuries and illnesses during the 1990s.
      The authors argue that far-reaching changes in the 1980s and 1990s, including the
      rise of precarious employment, falling wages and opportunities, and the creation
      of a super-vulnerable population of immigrant workers, probably helped create
      this apparent trend by preventing employees from reporting some injuries and
      illnesses. Changes in the health care system, including loss of access to health
      care for growing numbers of workers and increased obstacles to the use of
      workers' compensation, compounded these effects by preventing the diagnosis and
      documentation of some occupational injuries and illnesses. Researchers should
      examine these forces more closely to better understand trends in occupational
      health.

PMID- 15242160
TI  - Raw deal for workers: why have U.S. workers experienced a long-term decline in
      pay, benefits, and working conditions?
AB  - Pay, opportunities, and job quality have worsened for most U.S. workers over the
      past 30 years, across most sectors of the economy. This decline is related to
      fundamental changes in the economy and society, including sluggish productivity
      growth and employer assaults on workers' rights and protections. Productivity
      growth has slowed as companies no longer invest as much in equipment and
      training. Businesses have attacked workers' protections; unionization is down,
      and the minimum wage is worth about two-thirds as much as at its high point in
      the late 1960s. The National Labor Relations Board, other federal agencies, and
      the courts are stacked with anti-labor appointees. And businesses have pushed
      more and more risk onto workers, with a growth in temporary work and much reduced
      work-related benefits.

PMID- 15242161
TI  - The crisis of the Los Angeles County public hospital system: a harbinger for the
      nation.
AB  - The public hospital system in Los Angeles County, California, is in the midst of
      a major fiscal crisis that has already led to a serious reduction of capacity and
      could continue to worsen. Given the importance of the public system in a county
      where 30 percent of the population is uninsured and private hospitals provide
      very little uncompensated care, what happens in L.A. County is a harbinger for
      other cities and counties in the United States. This article highlights the issue
      of the extent to which local taxpayers, as opposed to state or federal taxpayers,
      are responsible for the continued operation of public hospitals and safety-net
      facilities in their communities.

PMID- 15242162
TI  - Political devolution and the health services in Great Britain.
AB  - This article reviews the effects of political devolution on health care in the
      countries of Great Britain at the end of the first term of the new political
      institutions created in 1999. In the light of the powers transferred, an
      assessment is made of the nature and extent of policy autonomy exercised by the
      devolved administrations. The author considers the question of whether political
      devolution is leading to local variations in health care provision that threaten
      established concepts of equity in a U.K. National Health Service. Policy areas
      discussed include the personal care of older people, mental health, governance,
      competition, the role of the private sector, and the health care workforce. Also
      discussed are the dynamics of intergovernmental relations in the longer term,
      including the effects of the developing European Union. The article concludes by
      assessing the extent to which the individual countries within Great Britain are
      likely to develop health care systems with distinctive identities.

PMID- 15242163
TI  - The politics of deteriorating health: the case of Palestine.
AB  - This article reviews the deteriorating health situation of the Palestinian
      population during the post-Oslo period of the Palestinian Authority and during
      the current Intifada. It seeks to record findings obtained through primary
      participants and documents and from personal observations in the field that
      situate Palestinian health conditions within their political framework. The
      ongoing crisis highlights longstanding problems in the Palestinian health
      infrastructure, which make it more vulnerable to Israeli policies, especially the
      movement restrictions and closures. Efforts by Palestinian professionals and the
      international health community to provide health services have been constantly
      thwarted. The Israeli authorities' disregard for Palestinian health care has
      escalated since 2000 and is directly responsible for a vast number of Palestinian
      deaths. Israel's indiscriminate obstructions to the coordinated functioning of a
      health care system in Palestine increase morbidity, degrade health, promote
      premature deaths, and damage the medical infrastructure. Moreover, the Israeli
      actions transgress international law and, ultimately, make peace in the region
      much less likely. This analysis provides further evidence of the social justice
      violations and the wide-ranging effects on health experienced daily by the
      Palestinian people as a direct result of the Israeli military occupation.

PMID- 15242164
TI  - An alternative to the neoliberal model in health: the case of Venezuela.
AB  - The authors present a synthesis of the proposals put forth by the health sector
      of Venezuela during the framing of the new Venezuelan Constitution. They
      summarize the background to the National Constituent Assembly and the legal
      framework typical of the health sector at that time, identify the methodological
      aspects that substantiated the health topics included in the new Constitution,
      and analyze the articles that shape the current constitutional health framework
      in Venezuela, summarizing their most important features and comparing them with
      neoliberal health proposals.

PMID- 15242165
TI  - The arabidopsis TIR-NB-LRR gene RAC1 confers resistance to Albugo candida (white
      rust) and is dependent on EDS1 but not PAD4.
AB  - Resistance to Albugo candida isolate Acem1 is conferred by a dominant gene, RAC1,
      in accession Ksk-1 of Arabidopsis thaliana. This gene was isolated by positional
      cloning and is a member of the Drosophila toll and mammalian interleukin-1
      receptor (TIR) nucleotide-binding site leucine-rich repeat (NB-LRR) class of
      plant resistance genes. Strong identity of the TIR and NB domains was observed
      between the predicted proteins encoded by the Ksk-1 allele and the allele from an
      Acem1-susceptible accession Columbia (Col) (99 and 98%, respectively). However,
      major differences between the two predicted proteins occur within the LRR domain
      and mainly are confined to the beta-strand/beta-turn structure of the LRR. Both
      proteins contain 14 imperfect repeats. RAC1-mediated resistance was analyzed
      further using mutations in defense regulation, including: pad4-1, eds1-1, and
      NahG, in the presence of the RAC1 allele from Ksk-1. White rust resistance was
      completely abolished by eds1-1 but was not affected by either pad4-1 or NahG.

PMID- 15242166
TI  - Glutamine utilization by Rhizobium etli.
AB  - We undertook the study of the use of glutamine (Gln) as the source of carbon and
      energy by Rhizobium etli. Tn5-induced mutagenesis allowed us to identify several
      genes required for Gln utilization, including those coding for two broad-range
      amino acid transporters and a glutamate dehydrogenase. The isolated mutants were
      characterized by the analysis of their capacity i) to grow on different media,
      ii) to transport Gln (uptake assays), and iii) to utilize Gln as the C energy
      source (CO2 production from Gln). We show that Gln is degraded through the citric
      acid cycle and that its utilization as the sole C source is related to a change
      in the bacterial cell shape (from bacillary to coccoid form) and a high
      susceptibility to a thiol oxidative insult. Both these data and the analysis of
      ntr-dependent promoters suggested that Gln-grown bacteria are under a condition
      of C starvation and N sufficiency, and as expected, the addition of glucose
      counteracted the morphological change and increased both the bacterial growth
      rate and their resistance to oxidative stress. Finally, a nodulation analysis
      indicates that the genes involved in Gln transport and degradation are
      dispensable for the bacterial ability to induce and invade developing nodules,
      whereas those involved in gluconeogenesis and nucleotide biosynthesis are
      strictly required.

PMID- 15242167
TI  - Differential gene expression in individual papilla-resistant and powdery mildew
      infected barley epidermal cells.
AB  - Resistance and susceptibility in barley to the powdery mildew fungus (Blumeria
      graminis f. sp. hordei) is determined at the single-cell level. Even in
      genetically compatible interactions, attacked plant epidermal cells defend
      themselves against attempted fungal penetration by localized responses leading to
      papilla deposition and reinforcement of their cell wall. This conveys a race
      nonspecific form of resistance. However, this defense is not complete, and a
      proportion of penetration attempts succeed in infection. The resultant mixture of
      infected and uninfected leaf cells makes it impossible to relate powdery mildew
      induced gene expression in whole leaves or even dissected epidermal tissues to
      resistance or susceptibility. A method for generating transcript profiles from
      individual barley epidermal cells was established and proven useful for analyzing
      resistant and successfully infected cells separately. Contents of single
      epidermal cells (resistant, infected, and unattacked controls) were collected,
      and after cDNA synthesis and PCR amplification, the resulting sample was
      hybridized to dot-blots spotted with genes, including some previously reported to
      be induced upon pathogen attack. Transcripts of several genes, (e.g., PR1a,
      encoding a pathogenesis related protein, and GLP4, encoding a germin-like
      protein) accumulated specifically in resistant cells, while GRP94, encoding a
      molecular chaperone, accumulated in infected cells. Thus, the single-cell method
      allows discrimination of transcript profiles from resistant and infected cells.
      The method will be useful for microarray expression profiling for simultaneous
      analysis of many genes.

PMID- 15242168
TI  - Soilborne wheat mosaic virus movement protein and RNA and wheat spindle streak
      mosaic virus coat protein accumulate inside resting spores of their vector,
      Polymyxa graminis.
AB  - To study virus-vector interactions between Soilborne wheat mosaic virus (SBWMV)
      or Wheat spindle streak mosaic virus (WSSMV) and Polymyxa graminis Ledingham, P.
      graminis was propagated in plants grown hydroponically. P. graminis accumulated
      to high levels in several barley cultivars tested. Multiple developmental stages
      of P. graminis could be identified in infected barley roots. Accumulation of
      SBWMV and WSSMV inside P. graminis sporosori in the roots of soil-grown winter
      wheat and hydroponically grown barley was compared to determine if data obtained
      from plants naturally infected plants and plants infected by manual inoculation
      were similar. WSSMV coat protein (CP), SBWMV RNAs, SBWMV movement protein but not
      SBWMV CP were detected in both soil-grown winter wheat and hydroponically grown
      barley roots. These data are the first direct evidence that SBWMV and WSSMV are
      internalized by P. graminis.

PMID- 15242169
TI  - RCH1, a locus in Arabidopsis that confers resistance to the hemibiotrophic fungal
      pathogen Colletotrichum higginsianum.
AB  - When challenged with the crucifer pathogen Colletotrichum higginsianum,
      Arabidopsis thaliana ecotype Columbia (Col-0) was colonized by the fungus within
      2 to 3 days, developing brown necrotic lesions surrounded by a yellow halo.
      Lesions spread from the inoculation site within 3 to 4 days, and subsequently
      continued to expand until they covered the entire leaf. Electron microscopy
      confirmed that C. higginsianum is a hemibiotroph on Arabidopsis, feeding
      initially on living cells as a biotroph before switching to a necrotrophic mode
      of growth. A collection of 37 ecotypes of Arabidopsis varied in their responses
      to infection by C. higginsianum. The ecotype Eil-0 was highly resistant, with
      symptoms limited to necrotic flecking and with only very limited fungal
      colonization. Analyses suggested that the hypersensitive response and reactive
      oxygen species may be important in this defense response. Expression analyses
      with cDNA microarrays indicated that the defense reaction depends primarily on
      the jasmonic acid- and ethylene-dependent signaling pathways and, to a lesser
      extent, on the salicylate-dependent pathway. Crosses between the Eil-0 and Col-0
      ecotypes suggested that the resistance in Eil-0 was dominant and was conferred by
      a single locus, which we named RCH1. RCH1 is the first resistance locus to be
      identified from Arabidopsis against the hemibiotrophic fungus genus
      Colletotrichum.

PMID- 15242170
TI  - Ethylene response factor 1 mediates Arabidopsis resistance to the soilborne
      fungus Fusarium oxysporum.
AB  - Ethylene response factor 1 (ERF1) is a transcriptional factor from Arabidopsis
      thaliana that regulates plant resistance to the necrotrophic fungi Botrytis
      cinerea and Plectosphaerella cucumerina and whose overexpression enhances
      resistance to these fungi. Here, we show that ERF1 also mediates Arabidopsis
      resistance to the soilborne fungi Fusarium oxysporum sp. conglutinans and F.
      oxysporum f. sp. lycopersici, because its constitutive expression in Arabidopsis
      confers enhanced resistance to these pathogens. Expression of ERF1 was
      upregulated after inoculation with F. oxysporum f. sp. conglutinans, and this
      response was blocked in ein2-5 and coi1-1 mutants, impaired in the ethylene (ET)
      and jasmonic acid (JA) signal pathways, respectively, which further indicates
      that ERF1 is a downstream component of ET and JA defense responses. The signal
      transduction network controlling resistance to F. oxysporum fungi was explored
      using signaling-defective mutants in ET (ein2-5), JA (jar1-1), and salicylic acid
      (SA) (NahG, sid2-1, eds5-1, npr1-1, pad4-1, eds1-1, and pad2-1) transduction
      pathways. This analysis revealed that Arabidopsis resistance to F. oxysporum
      requires the ET, JA, and SA signaling pathways and the NPR1 gene, although it is
      independent of the PAD4 and EDS1 functions.

PMID- 15242171
TI  - The avrRxo1 gene from the rice pathogen Xanthomonas oryzae pv. oryzicola confers
      a nonhost defense reaction on maize with resistance gene Rxo1.
AB  - Maize lines that contain the single dominant gene Rxo1 exhibit a rapid
      hypersensitive response (HR) after infiltration with the rice bacterial streak
      pathogen Xanthomonas oryzae pv. oryzicola, but not with the rice bacterial blight
      pathogen X. oryzae pv. oryzae. The avirulence effector gene that corresponds to
      Rxo1, designated avrRxo1, was identified in an X. oryzae pv. oryzicola genomic
      library. When introduced into X. oryzae pv. oryzae, clones containing avrRxo1
      induced an HR on maize with Rxo1, but not on maize without Rxo1. The avrRxo1 gene
      is 1,266 bp long and shows no significant homology to any database sequences.
      When expressed in an X. oryzae pv. oryzae hrpC mutant that is deficient in the
      type III secretion system, avrRxo1 did not elicit the HR, indicating that the
      avrRxo1-Rxo1 interaction is dependent on type III secretion. Transient expression
      of avrRxo1 in onion cells after biolistic delivery revealed that the protein
      product was associated with the plasma membrane. Transient expression in maize
      lines carrying Rxo1 resulted in cell death, suggesting that AvrRxo1 functions
      from inside maize cells to elicit Rxo1-dependent pathogen recognition.

PMID- 15242172
TI  - Inorganic cations mediate plant PR5 protein antifungal activity through fungal
      Mnn1- and Mnn4-regulated cell surface glycans.
AB  - Antimicrobial activities of many defense proteins are profoundly altered by
      inorganic cations, thereby controlling disease pathologies in a number of
      mammalian systems, such as cystic fibrosis in humans. Protein-based active
      defense systems in plants also are influenced by cations; however, little is
      known of how these cation effects are mediated. Cytotoxicity of the pathogenesis
      related protein osmotin against the model fungus Saccharomyces cerevisiae was
      progressively abolished by K+. By the use of S. cerevisiae mannosylation mutants,
      this effect was shown to require mannosephosphate residues in the cell wall.
      However, osmotin activity was not suppressed by even high concentrations of Ca2+.
      Rather, submillimolar levels of Ca2+ specifically facilitated osmotin's activity,
      as well as its binding to the cell surface. This effect also was dependent on
      mannosephosphate groups on the cell surface, and appeared to require negative
      charge on a portion of the osmotin protein. Results suggest that Ca2+ modulates
      osmotin action by facilitating its binding to the fungal cell surface, but that
      K+ blocks this interaction by competing for binding to mannosephosphate groups.
      Therefore, we have identified glycan interaction as a mechanism for antimicrobial
      protein activity modulation by cations, a pattern that may apply to diverse
      innate defense responses.

PMID- 15242173
TI  - Lotus japonicus LjKUP is induced late during nodule development and encodes a
      potassium transporter of the plasma membrane.
AB  - The KUP family of potassium transporters in plants is large but poorly
      characterized. We isolated and characterized the first KUP transporter from a
      legume, LjKUP of Lotus japonicus. Although expressed throughout plants, LjKUP
      transcript levels were highest in nodules. Induction of LjKUP expression occurred
      late during nodule development, at a time of rapid organ expansion. A high level
      of LjKUP expression was maintained in mature, full-sized nodules. However,
      induction of LjKUP expression was independent of symbiotic nitrogen fixation
      (SNF), and occurred in ineffective nodules resulting from mutations in either the
      plant or its microsymbiont, Mesorhizobium loti. Heterologous expression of LjKUP
      in Escherichia coli showed that the protein is able to transport potassium.
      Transient expression of a GFP-LjKUP fusion protein in Arabidopsis cells indicated
      a plasma membrane location for the transporter. Taken together, the results
      indicate that LjKUP is a potassium transporter of the plasma membrane, which may
      play roles in cell expansion during nodule development and in ion homeostasis
      during SNF.

PMID- 15242174
TI  - Introduction of plant and fungal genes into pea (Pisum sativum L.) hairy roots
      reduces their ability to produce pisatin and affects their response to a fungal
      pathogen.
AB  - Pisatin is an isoflavonoid phytoalexin synthesized by pea (Pisum sativum L.).
      Previous studies have identified two enzymes apparently involved in the synthesis
      of this phytoalexin, isoflavone reductase (IFR), which catalyzes an intermediate
      step in pisatin biosynthesis, and (+)6a-hydroxymaackiain 3-O-methyltransferase
      (HMM), an enzyme catalyzing the terminal step. To further evaluate the
      involvement of these enzymes in pisatin biosynthesis, sense- and antisense
      oriented cDNAs of Ifr and Hmm fused to the 35s CaMV promoter, and Agrobacterium
      rhizogenes, were used to produce transgenic pea hairy root cultures. PDA, a gene
      encoding pisatin demethylating activity (pda) in the pea-pathogenic fungus
      Nectria haematococca, also was used in an attempt to reduce pisatin levels.
      Although hairy root tissue with either sense or antisense Ifr cDNA produced less
      pisatin, the greatest reduction occurred with sense or antisense Hmm cDNA. The
      reduced pisatin production in these lines was associated with reduced amounts of
      Hmm transcripts, HMM protein, and HMM enzyme activity. Hairy roots containing the
      PDA gene also produced less pisatin. To evaluate the role of pisatin in disease
      resistance, the virulence of N. haematococca on the transgenic roots that
      produced the lowest levels of pisatin was tested. Hairy roots expressing
      antisense Hmm were more susceptible than the control hairy roots to isolates of
      N. haematococca that are either virulent or nonvirulent on wild-type pea plants.
      This appears to be the first case of producing transgenic plant tissue with a
      reduced ability to produce a phytoalexin and demonstrating that such tissue is
      less resistant to fungal infection: these results support the hypothesis that
      phytoalexin production is a disease resistance mechanism.

PMID- 15242175
TI  - Basal defenses induced in pepper by lipopolysaccharides are suppressed by
      Xanthomonas campestris pv. vesicatoria.
AB  - The nonpathogenic hrcC mutant of Xanthomonas campestris pv. vesicatoria 85
      10::hrpA22 multiplied in pepper leaves if it was mixed with pathogenic strains of
      X. campestris pv. vesicatoria. Reactions to the mutant alone included localized
      deposition of phenolics and callose in papillae, and alterations to the plant
      cell wall leading to increased electron density. Electron microscopy showed that
      the localized responses were suppressed in the presence of wild-type bacteria but
      other wall changes occurred at some sites, involving cellulose-rich ingrowth of
      the wall. Multiplication of the hrp mutant in mixed inocula was confirmed by
      tagging 85-10::hrpA22 using immunocytochemical location of AvrBs3 expressed from
      the plasmid pD36. Elicitors of callose deposition and other wall changes were
      isolated from the hrcC mutant. Activity in extracts of bacteria was attributed to
      the presence of high molecular weight lipopolysaccharides (LPS). Wild-type X.
      campestris pv. vesicatoria suppressed induction of structural changes caused by
      purified LPS. Results obtained suggest that effector proteins produced by
      phytopathogenic bacteria and delivered by the type III secretion system may have
      a key role in suppressing the basal defense responses activated by bacterial LPS,
      which lead to restricted multiplication of nonpathogens such as hrp mutants.

PMID- 15242177
TI  - Serological diagnosis of West Nile virus.

PMID- 15242176
TI  - Accumulation of lipochitin oligosaccharides and NodD-activating compounds in an
      efficient plant--Rhizobium nodulation assay.
AB  - During legume plant--Rhizobium spp. interactions, leading to the formation of
      nitrogen-fixing root nodules, the two major determinants of host plant
      specificity are plant-produced nod gene inducers (NodD protein activating
      compounds) and bacterial lipochitin oligosaccharides (LCOs or Nod factors). In a
      time course, we describe the accumulation of LCOs in an efficient nodulation
      assay with Vicia sativa subsp. nigra and Rhizobium leguminosarum, in connection
      with the presence of NodD-activating compounds in the exudate of V. sativa roots.
      Relatively small amounts of both LCOs and NodD-activating compounds were found to
      be required for initiation of nodulation during the first days after inoculation.
      A strong increase in the amount of NodRlv-V[18:4,Ac] LCOs preceded root infection
      and nodule primordium formation. In contrast to the situation with non-nodulating
      rhizobia and nonmitogenic LCOs, the amount of NodD-activating compounds in the
      culture medium remained small after addition of nodulating rhizobia or mitogenic
      LCOs. Furthermore, addition of nodulating rhizobia or mitogenic LCOs resulted in
      nearly complete inhibition of root hair formation and elongation, whereas
      nonmitogenic LCOs stimulated root hair growth. Retention of NodD-activating
      compounds in the root may inhibit root hair growth.

PMID- 15242178
TI  - AST and telepathology benefit labs.

PMID- 15242179
TI  - FISH and genetics advance bladder-cancer diagnosis.

PMID- 15242180
TI  - bioMerieux's Philippe Sans translates challenges into delivery. Interview by
      Dottie Dunham.

PMID- 15242181
TI  - Retention and ownership of blocks.

PMID- 15242182
TI  - A sixth-grader can do it.

PMID- 15242183
TI  - Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived
      radical-induced DNA damage and oxidative stress in human lymphocytes and rat
      liver cells.
AB  - The present study reports the protective effects of kolaviron, a Garcinia
      biflavonoid from the seeds of Garcinia kola widely consumed in some West African
      countries against oxidative damage to molecular targets ex-vivo and in vitro.
      Treatment with hydrogen peroxide (H2O2) at a concentration of 100 micromol/L
      increased the levels of DNA strand breaks and oxidized purine
      (formamidopyrimidine glycosylase (FPG) and pyrimidine (endonuclease III (ENDO
      III) sites) bases in both human lymphocytes and rat liver cells using alkaline
      single cell gel electrophoresis (the comet assay). Kolaviron was protective at
      concentrations between 30-90 micromol/L and decreased H2O2-induced DNA strand
      breaks and oxidized bases. Neither alpha-tocopherol nor curcumin decreased H2O2
      induced DNA damage in this assay. In lymphocytes incubated with Fe3+/GSH, Fe3+
      was reduced to Fe2+ by GSH initiating a free radical generating reaction which
      induced 11.7, 6.3, and 4.9 fold increase respectively in strand breaks, ENDO III
      and FPG sensitive sites compared with control levels. Deferoxamine (2 mmol/L), an
      established iron chelator significantly inhibited GSH/Fe3+-induced strand breaks
      and oxidized base damage. Similarly, kolaviron at 30 and 90 micromol/L
      significantly attenuated GSH/Fe3+-induced strand breaks as well as base
      oxidation. Kolaviron (100 mg/kg bw) administered to rats for one week protected
      rat liver cells against H2O2-induced formation of strand breaks, ENDO III, and
      FPG sensitive sites, Fe3+/EDTA/ascorbate-induced malondialdehyde formation and
      protein oxidation using gamma-glutamyl semialdehyde (GGS) and 2-amino-adipic
      semialdehyde (AAS) as biomarkers of oxidative damage to proteins. We suggest that
      kolaviron exhibits protective effects against oxidative damage to molecular
      targets via scavenging of free radicals and iron binding. Kolaviron may therefore
      be relevant in the chemoprevention of oxidant-induced genotoxicity and possibly
      human carcinogenesis.

PMID- 15242184
TI  - Genotoxicity of streptozotocin in normal and cancer cells and its modulation by
      free radical scavengers.
AB  - Streptozotocin (STZ) is an antibiotic which can be used to induce diabetes in
      experimental animals in order to have an insight into pathogenesis of this
      disease. To use STZ as a diabetogenic substance, its molecular mode of action
      should be elucidated. Using the alkaline comet assay, we showed that STZ at
      concentrations in the range 0.01-100 micromol/L induced DNA damage in normal
      human lymphocytes and HeLa cancer cells in a dose-dependent manner. Lymphocytes
      were able to remove damage to their DNA within a 30-min repair incubation,
      whereas HeLa cells completed the repair in 60 min. Vitamins C and E at 10 and 50
      micromol/L diminished the extent of DNA damage induced by 50 micromol/L STZ.
      Pretreatment of the lymphocytes with the nitrone spin trap, alpha-(4-pyridil-1
      oxide)-N-tert-butylnitrone (POBN) or ebselen, which mimics glutathione
      peroxidase, or pyrrolidine dithiocarbamate (PDTC) reduced the extent of DNA
      damage evoked by STZ. The cells exposed to STZ and treated with endonuclease III
      (Endo III), formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA
      glycosylase II (AlkA), the enzymes recognizing oxidized and alkylated bases,
      displayed greater extent of DNA damage than those not treated with these enzymes.
      These results suggest that free radicals may be involved in the formation of DNA
      lesions induced by streptozotocin. The drug can also alkylate DNA bases. This
      broad range of DNA damage induced by STZ indicates that the drug may seriously
      affect genomic stability in normal and pathological cells.

PMID- 15242185
TI  - Crystalline silica induces apoptosis in human endothelial cells in vitro.
AB  - We investigated whether incubation of cultured human aortic endothelial cells
      (HAEC) with crystalline silica at the concentration 1 cm2/ml (chosen on the basis
      of a pilot experiment) leads to alterations typical of apoptosis. The binding of
      annexin V as early, and DNA fragmentation as late events of apoptosis were
      measured besides the number of cells with depolarized mitochondria. The
      generation of reactive oxygen species (ROS) by HAEC in presence of silica was
      determined as well as silica ability to in vitro generate hydroxyl radicals was
      investigated. After 18 h of silica incubation, about 30% of viable cells bound
      annexin V. After 24 h of silica treatment, the percentage of cells with
      fragmented DNA (Tunel positive) was 27% and it increased up to 50% after 48 h,
      whereas in untreated cells this percentage was 7% and 11% after 24 and 48 h,
      respectively. The presence of fragmented DNA in cells treated with silica was
      confirmed by agarose gel electrophoresis. In agreement with these results showing
      an induction of HAEC apoptosis by silica incubation, the number of cells with
      depolarized mitochondria was significantly higher after silica treatment as
      compared to the control. Apoptosis was also obtained with silica added to
      aliquots of anti-C5a-absorbed-medium. In the cells exposed to silica there was a
      significant increasing of ROS generation in comparison to the untreated cells.
      Apoptosis might be due to peroxidative stress since silica can generate hydroxyl
      radicals.

PMID- 15242186
TI  - The effect of Smallanthus sonchifolius leaf extracts on rat hepatic metabolism.
AB  - Smallanthus sonchifolius (yacon), originating from South America, has become
      popular in Japan and in New Zealand for its tubers which contain beta-1,2
      oligofructans as the main saccharides. The plant is also successfully cultivated
      in Central Europe in the Czech Republic in particular. Its aerial part is used in
      Japan and in Brazil as a component in medicinal teas; while aqueous leaf extracts
      have been studied for their hypoglycemic activity in normal and diabetic rats. We
      have already demonstrated the high content of phenolic compounds in yacon leaf
      extracts and their in vitro antioxidant activity. In this paper, we present the
      effects of two organic fractions and two aqueous extracts from the leaves of S.
      sonchifolius on rat hepatocyte viability, on oxidative damage induced by tert
      butyl hydroperoxide (t-BH) and allyl alcohol (AA), and on glucose metabolism and
      their insulin-like effect on the expression of cytochrome P450 (CYP) mRNA. All
      the extracts tested exhibited strong protective effect against oxidative damage
      to rat hepatocyte primary cultures in concentrations ranging from 1 to 1000
      microg/ml, reduced hepatic glucose production via gluconeogenesis and
      glycogenolysis at 1000 microg/ml. Moreover, the effects of the organic fractions
      (200 and 250 microg/ml) and to a lesser extent, the tea infusion (500 microg/ml)
      on rat CYP2B and CYP2E mRNA expression, were comparable to those observed with
      insulin. The combination of radical scavenging, cytoprotective and anti
      hyperglycemic activity predetermine S. sonchifolius leaves for use in prevention
      and treatment of chronic diseases involving oxidative stress, particularly
      diabetes.

PMID- 15242187
TI  - Coffee-mediated protective effects against directly acting genotoxins and gamma
      radiation in mouse lymphoma cells.
AB  - The cytokinesis-block micronucleus test was performed using L5178Y mouse lymphoma
      cells to ascertain whether or not standard (caffeinated) instant coffee, the
      commonly consumed polyphenolic beverage with antioxidant activity can protect
      against chromosomal damage induced by the directly acting agents N-methyl-N-nitro
      N-nitrosoguanidine (MNNG), mitomycin C (MMC), methyl methanesulfonate (MMS) and
      gamma radiation. Our results demonstrated significant reductions in the in vitro
      genotoxic effects of MNNG, MMC, and MMS following co-treatment of mouse lymphoma
      cells with standard instant coffee. Subsequently, the comet assay was carried out
      to assess the effect of coffee co-treatment on the level of DNA damage induced by
      MMS in mouse lymphoma cells. The results demonstrated a significant reduction in
      MMS-induced DNA damage following co-treatment with standard instant coffee.
      Protective effects were observed in mouse lymphoma cells which were treated with
      coffee immediately after exposure to gamma radiation (1 and 2 Gy). Another
      experiment showed protection when the mammalian cells were irradiated (0.5 and 1
      Gy) midway (at 2 h) during a 4 h coffee treatment. However, the protective effect
      against the lower dose (0.5 Gy) was not significant. In addition we assessed the
      modulatory effect of coffee on MNNG-induced apoptotic frequency by flow
      cytometry. The results revealed only a minor influence of coffee on the frequency
      of apoptotic cells induced by the test compounds, rendering an increase in
      sensitivity for apoptosis as a reason for the reduced genomic damage an unlikely
      or at least incomplete explanation.

PMID- 15242188
TI  - Identifying patients with severe hospital-acquired infections due to
      Staphylococcus aureus by using the Healthcare Cost and Utilization Project
      (HCUP): problems and pitfalls.

PMID- 15242189
TI  - Evaluation of surgical-site infections following cardiovascular surgery.

PMID- 15242190
TI  - Is gastrointestinal endoscopy a risk factor for Whipple's disease?

PMID- 15242191
TI  - Is the burden of Staphylococcus aureus among patients with surgical-site
      infections growing?

PMID- 15242192
TI  - Surgical-site infection due to Staphylococcus aureus among elderly patients:
      mortality, duration of hospitalization, and cost.
AB  - OBJECTIVES: To examine the impact of surgical-site infection (SSI) due to
      Staphylococcus aureus on mortality, duration of hospitalization, and hospital
      charges among elderly surgical patients and the impact of older age on these
      outcomes by comparing older and younger patients with S. aureus SSI. DESIGN: A
      nested cohort study. SETTING: A 750-bed, tertiary-care hospital and a 350-bed
      community hospital. PATIENTS: Ninety-six elderly patients (70 years and older)
      with S. aureus SSI were compared with 2 reference groups: 59 uninfected elderly
      patients and 131 younger patients with S. aureus SSI. RESULTS: Compared with
      uninfected elderly patients, elderly patients with S. aureus SSI were at risk for
      increased mortality (odds ratio [OR], 5.4; 95% confidence interval [CI95], 1.5
      20.1), postoperative hospital-days (2.5-fold increase; CI95, 2.0-3.1), and
      hospital charges (2.0-fold increase; CI95, 1.7-2.4; dollar 41,117 mean
      attributable charges per SSI). Compared with younger patients with S. aureus SSI,
      elderly patients had increased mortality (adjusted OR, 2.9; CI95, 1.1-7.6),
      hospital-days (9 vs 13 days; P = .001), and median hospital charges (dollar
      45,767 vs dollar 85,648; P < .001). CONCLUSIONS: Among elderly surgical patients,
      S. aureus SSI was independently associated with increased mortality, hospital
      days, and cost. In addition, being at least 70 years old was a predictor of death
      in patients with S. aureus SSI.

PMID- 15242193
TI  - Sternal surgical-site infection following coronary artery bypass graft:
      prevalence, microbiology, and complications during a 42-month period.
AB  - OBJECTIVE: Surgical-site infection (SSI) is a serious and costly complication
      following coronary artery bypass graft (CABG). We analyzed surgical factors,
      microbiology, and complications at a 608-bed community teaching hospital to
      identify opportunities for prevention. METHODS: All patients undergoing CABG
      procedures from June 1997 through December 2000 were analyzed. Hospital records
      and postdischarge surveillance data were reviewed for demographics, surgical
      information, timing and classification of infection, microbiology, and bacteremic
      events. RESULTS: Of 3,443 patients undergoing CABG, sternal SSI developed in 122
      (3.5%); 71 (58.2%) were classified as superficial SSI and 51 (41.8%) as deep SSI.
      Surgical antimicrobial prophylaxis was employed in all cases. On average,
      infection occurred 21.5 days (range, 4 to 315) after CABG. Most cases were
      diagnosed on readmission (59%); 20 cases (16%) were identified by postdischarge
      surveillance. Microbiological data were positive in 109 (89.3%), with a single
      pathogen implicated in most (86.2%). Gram-positive cocci were most frequently
      recovered (81%); gram-negative bacilli (17%), gram-positive bacilli (1%), and
      yeast (1%) were less common. Staphylococcus aureus was the most frequently
      isolated pathogen (49%). Bacteremia was noted in 22 instances (18%). It was
      significantly associated with deep SSI (P =. 002) and identified only in S.
      aureus cases. CONCLUSIONS: SSI complicated 3.5% of the procedures. S. aureus was
      implicated in most of the cases and was significantly associated with deep SSI.
      It was the only pathogen associated with secondary bacteremia. In addition to
      standard guidelines, targeted methods against S. aureus should help reduce the
      overall rate of SSI.

PMID- 15242194
TI  - Surgical-site infection rates and risk factor analysis in coronary artery bypass
      graft surgery.
AB  - BACKGROUND: The Victorian Infection Control Surveillance Project (VICSP) is a
      multicenter collaborative surveillance project established by infection control
      practitioners. Five public hospitals contributed data for patients undergoing
      coronary artery bypass graft (CABG) surgery. OBJECTIVE: To determine the
      aggregate and comparative interhospital surgical-site infection (SSI) rates for
      patients undergoing CABG surgery and the risk factors for SSI in this patient
      group. METHOD: Each institution used standardized definitions of SSI, risk
      adjustment, and reporting methodology according to the National Nosocomial
      Infections Surveillance System of the Centers for Disease Control and Prevention.
      Data on potential risk factors were prospectively collected. RESULTS: For 4,474
      patients undergoing CABG surgery, the aggregate SSI rate was 7.8 infections per
      100 procedures (95% confidence interval [CI95], 7.0-8.5), with individual
      institutions ranging between 4.5 and 10.7 infections per 100 procedures.
      Multivariate risk factor analysis demonstrated age (odds ratio [OR], 1.02; CI95,
      1.01-1.04; P < .001), obesity (OR, 1.8; CI95, 1.4-2.3; P < .001), and diabetes
      mellitus (OR, 1.6; CI95, 1.2-2.1; P < .001) as independent predictors of SSI.
      Three hundred thirty-four organisms were isolated from 296 SSIs. Of the total
      SSIs, methicillin-resistant Staphylococcus aureus was isolated from 32%,
      methicillin-sensitive S. aureus from 24%, gram-negative bacilli (eg, Enterobacter
      and Escherichia coli) from 18%, and miscellaneous organisms from the remainder.
      CONCLUSION: We documented aggregate and comparative SSI rates among five
      Victorian public hospitals performing CABG surgery and defined specific
      independent risk factors for SSI. VICSP data offer opportunities for targeted
      interventions to reduce SSI following cardiac surgery.

PMID- 15242195
TI  - Risk factors for surgical-site infection following primary total knee
      arthroplasty.
AB  - OBJECTIVE: To identify risk factors associated with the development of surgical
      site infection (SSI) following total knee arthroplasty (TKA). DESIGN: A case
      control study. SETTING: A 1,100-bed, university-affiliated, tertiary-care
      teaching hospital. METHODS: Case-patients with SSI occurring up to 1 year
      following primary TKA performed between January 1999 and December 2001 were
      identified prospectively by infection control practitioners using National
      Nosocomial Infections Surveillance (NNIS) System methods. Three control-patients
      were selected for each case-patient, matched by date of surgery. Stepwise
      logistic regression analysis was used to determine the relation of potential risk
      factors to the development of infection. RESULTS: Twenty-two patients with
      infections (6 superficial and 16 deep) were identified. Infection rates per year
      were 0.95%, 1.07%, and 1.19% in 1999, 2000, and 2001, respectively. Logistic
      regression analysis identified two variables independently associated with the
      development of infection: the use of closed suction drainage (odds ratio [OR],
      7.0; 95% confidence interval [CI95], 2.1-25.0; P = .0015) and increased
      international normalized ratio (INR) (OR, 2.4; CI95, 1.1-5.7; P = .035). Factors
      not statistically associated with the development of infection included age, NNIS
      System risk index score, presence of various comorbidities, surgeon, duration of
      procedure or tourniquet time, type of bone cement or prosthesis used, or receipt
      of blood product transfusions. CONCLUSIONS: The use of closed suction drainage
      and a high postoperative INR were associated with the development of SSI
      following TKA. Avoiding the use of surgical drains and careful monitoring of
      anticoagulant prophylaxis in patients undergoing TKA should reduce the risk of
      infection.

PMID- 15242196
TI  - Preoperative risk factors for nasal carriage of Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus nasal carriage is a risk factor for surgical
      site infections (SSIs) caused by S. aureus, and eradication of carriage reduces
      postoperative nosocomial infections caused by it. No study has compared large
      groups of preoperative carriers and non-carriers to identify factors that are
      linked to S. aureus nasal carriage. METHODS: While conducting a clinical trial
      evaluating whether mupirocin prevented S. aureus SSIs, we prospectively collected
      data on 70 patient characteristics that might be associated with S. aureus
      carriage. We performed stepwise logistic regression analysis. RESULTS: Of the
      4,030 patients, 891 (22%) carried S. aureus. Independent risk factors for S.
      aureus nasal carriage were obesity (odds ratio [OR], 1.29; 95% confidence
      interval [CI95], 1.11-1.50), male gender (OR, 1.29; CI95, 1.11-1.51), and a
      history of a cerebrovascular accident (OR, 1.53; CI95, 1.03-2.25) for all
      patients. Factors associated with nasal carriage varied somewhat by surgical
      specialty. In all groups, preoperative use of antimicrobial agents was
      independently associated with a lower risk of carrying S. aureus in the nares.
      Previously identified risk factors were not significantly associated with S.
      aureus nasal carriage in this large group of surgical patients. CONCLUSION: Male
      gender, obesity, and a history of a cerebrovascular accident were identified as
      risk factors for S. aureus nasal carriage. It remains to be seen whether
      preoperative weight loss would reduce the rate of nasal carriage. In addition,
      the value of screening this patient population for S. aureus nasal carriage
      merits further investigation.

PMID- 15242197
TI  - Staphylococcus aureus nasal carriage in a student community: prevalence, clonal
      relationships, and risk factors.
AB  - OBJECTIVE: To evaluate the prevalence and risk factors of nasal Staphylococcus
      aureus (SA) in the community. DESIGN: Cross-sectional study. SETTING: Wake Forest
      University, Winston-Salem, North Carolina. PARTICIPANTS: Four hundred fifty
      students were screened for nasal SA carriage during the fall of 2000, 2001, and
      2002. METHODS: Students were screened by nose swabs. A self-administered
      questionnaire collected information on demographics and medical history.
      Antibiotic testing and PFGE were performed on isolates. Risk factors were
      determined by logistic regression analysis. RESULTS: Of 450 volunteers, 131 (29%)
      were SA carriers. Antibiotic resistance was high for azithromycin (26%) and low
      for ciprofloxacin (1%), tetracycline (5%), mupirocin (1%), and methicillin (2%).
      PFGE patterns were not associated with carriage. Age, male gender, white race,
      medical student, allergen injection therapy, chronic sinusitis, rheumatoid
      arthritis, hospitalization for 6 months or less, and use of antibiotics were
      associated with carrier status by univariate analysis. Stepwise multivariate
      logistic regression led to a best fitting model with older age (OR, 1.04; CI95,
      1.005-1.079), male gender (OR, 1.50; CI95, 0.982-2.296), and chronic sinusitis
      (OR, 2.71; CI95, 0.897-8.195) as risk factors. Antibiotic use (< 4 weeks) (OR,
      0.41; CI95, 0.152-1.095) and allergen injection therapy (OR, 0.41; CI95, 0.133
      1.238) were protective. Analyses of carriers revealed candidate factors for
      persistent carriage to be nasal SA colonization rate and male gender. Factors for
      azithromycin resistance were non-medical students and antibiotic use in the past
      6 months. CONCLUSION: Older male volunteers suffering from chronic sinusitis and
      not taking antibiotics were at higher risk for carrying SA.

PMID- 15242198
TI  - Prevention of infections associated with permanent cardiac antiarrhythmic devices
      by implementation of a comprehensive infection control program.
AB  - OBJECTIVE: To implement a comprehensive infection control (IC) program for
      prevention of cardiac device-associated infections (CDIs). DESIGN: Prospective
      before-after trial with 2 years of follow-up. SETTING: A tertiary-care,
      university-affiliated medical center. PATIENTS: A consecutive sample of all
      adults undergoing cardiac device implantation between 1997 and 2002.
      INTERVENTION: An IC program was implemented during late 2001 and included staff
      education, preoperative modification of patient risk factors, intraoperative
      control of strict aseptic technique, surgical scrubbing and attire, control of
      environmental risk factors, optimization of antibiotic prophylaxis, postoperative
      wound care, and active surveillance. The clinical endpoint was CDI rates.
      RESULTS: Between 1997 and 2000, there were 7 CDIs among 725 procedures (mean
      annual CDI incidence, 1%). During the first 9 months of 2001, there were 7 CDIs
      among 167 procedures (4.2%; P = .007): CDIs increased from 7 among 576 to 3 among
      124 following pacemaker implantation (P = .39) and from 0 among 149 to 4 among 43
      following cardioverter-defibrillator implantation (P = .002). Of the 14 CDIs, 5
      involved superficial wounds, 7 involved deep wounds, and 2 involved endocarditis.
      Following intervention, there were no cases of CDI among 316 procedures during 24
      months of follow-up (4.2% reduction; P = .0005). CONCLUSIONS: We observed a high
      CDI rate associated with substantial morbidity. IC measures had an impact on CDI.
      Although the relative weight of each measure in the prevention of CDI remains
      unknown, our results suggest that implementation of a comprehensive IC program is
      feasible and efficacious in this setting.

PMID- 15242199
TI  - A protracted outbreak of Staphylococcus epidermidis infections among patients
      undergoing valve replacement.
AB  - OBJECTIVE: To investigate a Staphylococcus epidermidis outbreak among patients
      undergoing cardiac surgery. DESIGN: Retrospective cohort study. SETTING: A 260
      bed community referral center. PATIENTS: Case-patients were patients with S.
      epidermidis mediastinitis, endocarditis, or both after valve implantation at
      Hospital de La Ribera from January to June 2002. The study population included
      patients undergoing valve surgery at Hospital de La Ribera from January 2000 to
      June 2002. RESULTS: From January to June 2002, 8 cases of mediastinitis,
      endocarditis, or both occurred among 53 patients undergoing cardiac surgery. In
      the same months of 2000, there had been no cases among 22 patients, and in 2001,
      only 1 case among 47 patients (P = .095 and P = .034, respectively). In 2002,
      there were 4 cases of mediastinitis and endocarditis, 3 cases of mediastinitis,
      and 1 case of endocarditis, all following aortic valve replacement. The epidemic
      curve suggested a protracted outbreak. Patients with chronic obstructive lung
      disease were six-fold more likely to be case-patients (95% confidence interval,
      1.6-23.8). The mean duration of surgery tended to be longer in non-case-patients
      (161.4 +/- 57.9 minutes) than in case-patients (123.7 +/- 23.7 minutes) (P =
      .06). CONCLUSION: The cause of this protracted outbreak was likely
      multifactorial. Reemphasis of existing policies was associated with resolution of
      the outbreak.

PMID- 15242200
TI  - Airborne dispersal as a novel transmission route of coagulase-negative
      staphylococci: interaction between coagulase-negative staphylococci and
      rhinovirus infection.
AB  - OBJECTIVE: To investigate whether rhinovirus infection leads to increased
      airborne dispersal of coagulase-negative staphylococci (CoNS). DESIGN:
      Prospective nonrandomized intervention trial. SETTING: Wake Forest University
      School of Medicine, Winston-Salem, North Carolina. PARTICIPANTS: Twelve nasal
      Staphylococcus aureus-CoNS carriers among 685 students screened for S. aureus
      nasal carriage. INTERVENTIONS: Participants were studied for airborne dispersal
      of CoNS in a chamber under three conditions (street clothes, sterile gown with a
      mask, and sterile gown without a mask). After 2 days of pre-exposure
      measurements, volunteers were inoculated with a rhinovirus and observed for 14
      days. Daily quantitative nasal and skin cultures for CoNS and nasal cultures for
      rhinovirus were performed. In addition, assessment of cold symptoms was performed
      daily, mucous samples were collected, and serum titers before and after
      rhinovirus inoculation were obtained. Sneezing, coughing, and talking events were
      recorded during chamber sessions. RESULTS: All participants had at least one
      nasal wash positive for rhinovirus and 10 developed a symptomatic cold.
      Postexposure, there was a twofold increase in airborne CoNS (P = .0004), peaking
      at day 12. CoNS dispersal was reduced by wearing a gown (57% reduction, P <
      .0001), but not a mask (P = .7). Nasal and skin CoNS colonization increased after
      rhinovirus infection (P < .05). CONCLUSIONS: We believe this is the first
      demonstration that a viral pathogen in the upper airways can increase airborne
      dispersal of CoNS in nasal S. aureus carriers. Gowns, gloves, and caps had a
      protective effect, whereas wearing a mask did not further reduce airborne spread.

PMID- 15242201
TI  - The value of bacterial culture during clean orthopedic surgery: a prospective
      study of 1,036 patients.
AB  - OBJECTIVE: To determine whether bacterial cultures of the wounds of patients
      undergoing clean orthopedic surgery would help predict infection. METHODS: During
      1 year, 1,256 cultures were performed for 1,102 patients who underwent clean
      orthopedic surgery. Results were analyzed to evaluate their ability to predict
      postoperative infection. RESULTS: The sensitivity, specificity, positive
      predictive value, and negative predictive value of the cultures were 38%, 92%,
      7%, and 99%, respectively. CONCLUSIONS: Cultures performed during clean
      orthopedic surgery were not useful for predicting postoperative infection.

PMID- 15242202
TI  - Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among
      patients with femoral neck fractures: implication for antibiotic prophylaxis.
AB  - Fifteen (8.4%) of 179 patients admitted with femoral neck fractures carried MRSA.
      Among 96 patients admitted from their homes, only 2 (2%) were carriers, whereas
      13 (15.6%) of 83 patients from nursing or residential homes or long-term-care
      facilities were colonized (P = .001). Routine prophylaxis with vancomycin is
      recommended in the latter group.

PMID- 15242203
TI  - Improving outcomes of coronary artery bypass graft infections with multiple
      interventions: putting science and data to the test.
AB  - In 2001, 7.58% of our coronary artery bypass graft (CABG) patients developed
      surgical-site infection (SSI) as compared with 3.57% in National Nosocomial
      Infections Surveillance System hospitals from January 1992 to June 2001. Seven
      new preventive measures were implemented and in 2002, the rate was 3.47%.
      Implementing evidence-based measures improved patient outcomes.

PMID- 15242204
TI  - Is it necessary to shave the pubic and genital regions of patients undergoing
      endoscopic urological surgery?
AB  - To determine whether postoperative urinary infections were related to shaving
      before undergoing endoscopic urological surgery, 90 patients were randomly
      assigned to shaving or not shaving. Urinary cultures revealed infection in 10
      patients. Half of them had been shaved, suggesting that this practice does not
      affect the incidence of urinary infections.

PMID- 15242205
TI  - Sexuality, rights and social justice.

PMID- 15242206
TI  - Implementing the ICPD Programme of Action: what a difference a decade makes.
AB  - The Programme of Action adopted at the International Conference on Population and
      Development in Cairo in 1994 was conceived as a 20-year programme. Now, at its
      mid-point in 2004, we have reached a time for assessment and re-commitment to its
      goals. This paper is a reflection on some of the political and other changes that
      have taken place during the first ten years of the Programme of Action and their
      implications for its implementation in the coming decade. Many countries have
      gone ahead and integrated sexual and reproductive health services into primary
      health care, whether or not the concept has been supported at the international
      level, and are doing what they can to accommodate the needs of those requiring
      information and services. The shape of the "playing field" has changed in the
      past ten years and the goal posts have moved. Yet many countries are adjusting
      and adapting. The big question, which has yet to be answered, is whether the
      international community will help or hinder the efforts at country level to
      achieve the goal of access for all to sexual and reproductive health by 2015.

PMID- 15242207
TI  - Psychosexual development among HIV-positive adolescents in Abidjan, Cote
      d'Ivoire.
AB  - Some 84,000 children with HIV/AIDS live in Cote d'Ivoire, where very little
      therapeutic or psychological help is available to them. The Yopougon Child
      Programme of the "Agence Nationale de Recherche sur le Sida" was launched in
      Abidjan in October 2000. It provides services for HIV-infected children and
      psychological consultations for children and their parents. This paper is about
      the psychosexual development of the HIV-positive adolescents in the Programme, 11
      girls and 8 boys aged 13-17, their problems with HIV-related physiological and
      psychosexual changes, and relationships with their parents. The information was
      gathered in individual therapy sessions, group discussions and family support
      sessions. Bodily development was of major importance to these adolescents,
      particularly among those who had not yet developed secondary sexual
      characteristics and were shorter and weighed less than their peers. Those who had
      not achieved puberty were unable to participate in traditional rituals and
      worried whether they could ever marry or have children. In most cases,
      adolescents with HIV have been infected by a sexually transmitted virus without
      having had sexual relations themselves. They need support dealing with their
      sexual development and sexual feelings, along with medical care, in a context in
      which HIV infection is a secret, impossible to talk about with their peers.

PMID- 15242208
TI  - "Peer" educator initiatives for adolescent reproductive health projects in
      Indonesia.
AB  - Since the ICPD in 1994, the Government of Indonesia has struggled with the
      challenge of providing sexual and reproductive health education to adolescents.
      Following an attempt at a family-centred approach, a pilot project was carried
      out in Central and East Java to train peer educators, coordinated by the National
      Family Planning Coordinating Board (BKKBN). A total of 80 peer educators
      (male/female teams) carried out small-group information sessions in ten different
      districts. Over 1,300 adolescents attended in all. Forty peer counsellors in 20
      teams then carried out five outreach sessions each in their communities, attended
      by nearly 4,000 adults and adolescents. Educators chosen were older in age,
      knowledge level, authority and communication skills than adolescents, but were
      well accepted as mentors. Adolescents wanted to know how to deal with sexual
      relationships and feelings, unwanted pregnancy and STDs. With 42 million
      Indonesian adolescents needing information, the government cannot produce enough
      manuals to satisfy demand. New strategies are required to put information in the
      public domain, e.g. via the media. The approach described in this paper would
      probably be beyond the staffing and resource capacity of most districts in
      Indonesia. Nonetheless, it shows that there was great enthusiasm across a variety
      of communities for efforts to educate young people on protecting their
      reproductive health.

PMID- 15242209
TI  - Youth, sexuality and sex education messages in Indonesia: issues of desire and
      control.
AB  - Since the 1994 International Conference on Population and Development, the need
      for sexuality education for youth has been articulated, and numerous activities
      in Indonesia, especially Java, have been directed at young people. However, many
      parents, teachers and religious leaders have considered it essential that such
      education should suppress youth sexuality. This article reflects upon current
      discourses on youth sexuality in Java as against the actual sexual behaviour of
      young people. Using examples from popular magazines and educational publications,
      and focus group discussions with young men and women in Surabaya, East Java, we
      argue that the dominant prohibitive discourse in Java denounces youth sexuality
      as unhealthy, reinforced through intimidation about the dangers of sex. In
      contrast, a discourse of competence and citizenship would more adequately reflect
      the actual sexual behaviour of youth, and raises new challenges for sexuality
      education. Information should be available to youth concerning different
      sexualities, respecting the spectrum of diversity. Popular youth media have an
      especially important role to play in this. The means to stay healthy and be
      responsible--contraceptives and condoms--should be available at sites where youth
      feel comfortable about accessing them. Meanwhile, young Indonesians are engaging
      in different forms of sexual relationships and finding their own sources of
      information, independent of government, religion and international organisations.

PMID- 15242210
TI  - Sex workers in Kenya, numbers of clients and associated risks: an exploratory
      survey.
AB  - In Kenya in 1999, an estimated 6.9% of women nationally said they had exchanged
      sex for money, gifts or favours in the previous year. In 2000 and 2001, in
      collaboration with sex workers who had formed a network of self-help groups, we
      conducted an exploratory survey among 475 sex workers in four rural towns and
      three Nairobi townships, regarding where they worked, the number of clients they
      had and the risks they were exposed to. Participants were identified by a network
      of social contacts in the seven centres. Most of the women (88%) worked from
      bars, hotels, bus stages and discos; 57% lived with a stable partner and almost
      90% had dependent children. In the previous month, 17% had been assaulted and 35%
      raped by clients. Unwanted pregnancy was common; 86% had had at least one
      abortion. Compared with women in rural towns, township sex workers were younger
      (median age 22 vs. 26), saw more clients (median 9 vs. 4 per week) and earned
      more from sex work (up to 63-90 euros vs. 12 euros per week). Issues of
      alternative sources of income, safety for sex workers and the conditions which
      create the necessity for sex work are vital to address. The question of number of
      clients and the nature of sex work have obvious implications for HIV/STI
      prevention policy.

PMID- 15242211
TI  - Searching for justice for body and self in a coercive environment: sex work in
      Kerala, India.
AB  - Sex workers in Kerala, India, live in a coercive environment and face violence
      from the police and criminals, lack of shelter, lack of childcare support and
      have many physical and mental health problems. This paper documents the
      environment in which women have been selling sex in Kerala since 1995, and their
      efforts to claim their rights. It is based on sex workers' own reports and
      experiences, a situation analysis and a needs assessment study by the Foundation
      for Integrated Research in Mental Health. Involvement in HIV/AIDS prevention
      projects first gave sex workers in Kerala an opportunity to come together. Some
      have become peer educators and distribute condoms but they continue to be
      harassed by police. Most anti-trafficking interventions, including rescue and
      rehabilitation, either criminalise or victimise sex workers, and sex workers
      reject them as a solution to sex work. They understand that the lack of sexual
      fulfillment in other relationships and their own lack of access to other work and
      resources are the reasons why commercial sex flourishes. Sex workers are not mere
      victims without agency. They have a right to bodily integrity, pleasure,
      livelihood, self-determination and a safe working environment. Sex workers are
      organising themselves for these objectives and demand decriminalisation of sex
      work.

PMID- 15242212
TI  - Sexual torture of men in Croatia and other conflict situations: an open secret.
AB  - Sexual torture constitutes any act of sexual violence which qualifies as torture.
      Public awareness of the widespread use of sexual torture as a weapon of war
      greatly increased after the war in the former Yugoslavia in the early 1990s.
      Sexual torture has serious mental, physical and sexual health consequences.
      Attention to date has focused more on the sexual torture of women than of men,
      partly due to gender stereotypes. This paper describes the circumstances in which
      sexual torture occurs, its causes and consequences, and the development of
      international law addressing it. It presents data from a study in 2000 in
      Croatia, where the number of men who were sexually tortured appears to have been
      substantial. Based on in-depth interviews with 16 health professionals and data
      from the medical records of three centres providing care to refugees and victims
      of torture, the study found evidence of rape and other forced sexual acts, full
      or partial castration, genital beatings and electroshock. Few men admit being
      sexually tortured or seek help, and professionals may fail to recognise cases.
      Few perpetrators have been prosecuted, mainly due to lack of political will. The
      silence that envelopes sexual torture of men in the aftermath of the war in
      Croatia stands in strange contrast to the public nature of the crimes themselves.

PMID- 15242213
TI  - Sexuality and women's rights in armed conflict in Sri Lanka.
AB  - The discourse of human rights in armed conflict situations is well adapted to
      respond to violence and violation, invoking internationally agreed principles of
      civil and political rights. However, in areas where the subject or domain of
      rights discourse is contested or controversial, human rights advocates appear
      less prepared to promote and defend such rights. Sexuality is one such domain.
      This paper explores the complex sexual choices women in Sri Lanka have had to
      negotiate, particularly widows and sex workers, within a context of ethnic
      conflict, militarisation and war. It argues that sexuality cannot be defined
      exclusively in terms of violation, even in a context dominated by violence, and
      that the sexual ordering of society may be subverted in such conditions. Newly
      widowed women and sex workers have had to negotiate self-determination as well as
      take responsibility for earning income and heading households, in spite of
      contrary community pressures. For women, political and economic rights are
      closely linked with the ability to determine their sexual and reproductive
      choices. The challenge to women's and human rights advocates is how to articulate
      sexual autonomy as a necessary right on a par with others, and strategise to
      secure this right during armed conflict and postwar reconstruction.

PMID- 15242214
TI  - "Yes" to abortion but "no" to sexual rights: the paradoxical reality of married
      women in rural Tamil Nadu, India.
AB  - This study in rural Tamil Nadu, India, explored the reasons why many married
      women in India undergo induced abortions rather than use reversible contraception
      to space or limit births in terms of women's sexual and reproductive rights
      within marriage, and in the context of gender relations between couples more
      generally. It is based on in-depth interviews with two generations of ever
      married women, some of whom had had abortions and others who had not, from 98
      rural hamlets. The respondents were 66 women and 44 of their husbands. Non
      consensual sex, sexual violence and women's inability to refuse their husband's
      sexual demands appeared to underlie the need for abortion in both younger and
      older women. Many men seemed to believe that sex within marriage was their right,
      and that women had no say in the matter. The findings raise questions about the
      presumed association between legal abortion and the enjoyment of reproductive and
      sexual rights. A large number of women who had abortions in this study were
      denied their sexual rights but were permitted, even forced, to terminate their
      pregnancies for reasons unrelated to their right to choose abortion. The study
      brings home the need for activism to promote women's sexual rights and a campaign
      against sexual violence in marriage.

PMID- 15242216
TI  - The prosecution of Taiwan sexuality researcher and activist Josephine Ho.
AB  - In April 2003, following a newspaper report of a hyperlink to a website on
      bestiality on the Sexuality Databank website of the Center for the Study of
      Sexualities, National Central University, Taipei, Taiwan, 14 conservative NGOs
      filed charges against the Center's founder, Josephine Ho, for "propagating
      obscenities that corrupt traditional values." Ho has been researching sexuality
      and supporting freedom for marginalised sexual minorities for ten years. In a
      public statement in response to the charges, she said that the work of scholarly
      research must not be dictated by prejudice and that differences in sexual values
      should not be arbitrated by law and should be open for public discussion. As the
      legal process began in January 2004, Ho's supporters in Taiwan have called for
      the preservation of the Taiwan Constitutional decree on integrity and autonomy of
      academic research and freedom of expression on the internet, for the University
      to resist calls to dismiss Ho from her post, and for respect for freedom of
      speech and expression and the right to create spaces to educate people about non
      normative sexualities.

PMID- 15242215
TI  - "The cut above" and "the cut below": the abuse of caesareans and episiotomy in
      Sao Paulo, Brazil.
AB  - In the last 50 years, a rapid increase in the use of technology to start,
      augment, accelerate, regulate and monitor the process of birth has frequently led
      to the adoption of inadequate, unnecessary and sometimes dangerous interventions.
      Although research has shown that the least amount of interference compatible with
      safety is the paradigm to follow, vaginal birth is still being treated as if it
      carries a high risk to women's health and sexual life in Brazil. This paper
      describes the impact of the intervention model on women's birth experience, and
      discusses how the organisation of public and private maternity services in Brazil
      influences the quality of obstetric care. Brazil is known for high rates of
      unnecessary caesarean section ("the cut above"), performed in over two-thirds of
      births in the private sector, where 30% of women give birth. The 94.2% rate of
      episiotomy ("the cut below") in women who give birth vaginally, affecting the 70%
      of poor women using the public sector most, receives less attention. A change in
      the understanding of women's bodies is required before a change in the procedures
      themselves can be expected. Since 1993, inspired by campaigns against female
      genital mutilation, a national movement of providers, feminists and consumer
      groups has been promoting evidence-based care and humanisation of childbirth in
      Brazil, to reduce unnecessary surgical procedures.

PMID- 15242217
TI  - Betrayal.
AB  - Equality for women was non-existent in Taliban-controlled Afghanistan. Today,
      although girls and women in Kabul and some other cities are free to go to school
      and have jobs, this is not the case in most parts of the country. Armed local
      warlords have their own rules and governments which brutalize people--especially
      women. In some areas where girls' education does exist, parents are too afraid to
      allow their daughters to take advantage of it, following the burning down of
      several girls' schools. Girls have been abducted on the way to school, and sexual
      assaults on children of both sexes are now commonplace. The "war on terrorism"
      has toppled the Taliban, but with the warlords back in power, one misogynist
      fundamentalist regime has been replaced with another. Yet there is resistance.
      Last year, strong voices of opposition against fundamentalists were heard from
      the women in the traditional Loya Jirga assembly. And the Revolutionary
      Association of Women of Afghanistan (RAWA) is continuing its efforts towards
      freedom, democracy, secularism and women's rights. Afghan women cannot fight for
      their rights without education. For this reason, we have concentrated on raising
      awareness, organizing women in the legal and social sectors, and increasing
      education and literacy among them. Armed with education, Afghan women cannot
      continue to be ignored.

PMID- 15242218
TI  - Holy hatred.
AB  - There are at least 83 countries where homosexuality is condemned in the criminal
      code; 26 of these are Muslim countries and in seven the death penalty for persons
      presumed guilty of homosexual acts makes sexual minorities extremely vulnerable.
      In spite of such obstacles, same-sex relationships do take place, even in the
      most repressive countries. Sometimes the very segregation of the sexes allows for
      intimacy between people of the same sex without it being considered abnormal.
      There are positive examples of same-sex relationships to be found in different
      Muslim cultures, e.g. in travelling theatre and musical groups and in poetry.
      Controversy regarding the position of Islam on homosexuality is ongoing, as the
      Qur'an is far from clear on the issue. There is also a strong connection between
      homophobic assaults by fundamentalists and those directed against women who do
      not "behave." Sexuality and sexual conformity may be the focus of attention by
      fundamentalist forces because individual choice and autonomy, especially for
      women, is seen as a threat. Despite a threatening environment, sexual minorities
      are organising and becoming more visible in Muslim countries and communities;
      whether mainly political, social or religious in their motivation, these
      organisations all aim at breaking the isolation faced by sexual minorities.

PMID- 15242219
TI  - Sexual and bodily rights as human rights in the Middle East and North Africa.
AB  - A regional workshop on sexual and bodily rights as human rights in the Middle
      East and North Africa was held in Malta in 2003, attended by 22 NGO
      representatives from Jordan, Egypt, Lebanon, Palestine, Tunisia, Morocco,
      Algeria, Turkey, Pakistan and USA. The meeting aimed to develop strategies for
      overcoming human rights violations in the region with reference to law and social
      and political practices. Session topics included sexuality and gender identity;
      sexuality and sexual health; sexuality and comparative penal law; sexual rights
      in international documents; advocacy and lobbying. Sexual rights, sexual health
      and education, sexual violence and adolescent sexuality were explored in depth,
      including taboos and emerging trends. Specific areas of concern included marital
      rape, early marriages, temporary marriages, sexual orientation, premarital and
      extramarital sexuality, honour crimes, female genital mutilation, unmarried
      mothers, adolescent sexuality, unwanted pregnancies and safe abortion, sexuality
      in education and health services. An analysis of civil codes, penal codes and
      personal status codes indicated a clear imperative for legal reform. Participants
      heard about efforts to promote the right to sexual orientation which have already
      been initiated in Lebanon, Turkey and Tunisia. Networking within the region and
      with counterparts in other regions in comparable situations and conditions was
      deemed essential.

PMID- 15242220
TI  - A, B and C in Uganda: the roles of abstinence, monogamy and condom use in HIV
      decline.
AB  - Uganda is often cited as a role model in the fight against HIV/AIDS because of
      its success in reducing both prevalence and incidence of HIV infection since the
      late 1980s. Although an increase in sexual abstinence has been highlighted as a
      primary cause of the declines, large increases have also been recorded in
      monogamy and condom use. The extent to which each of these factors actually
      influenced the overall decline in Uganda's HIV rates has become a highly charged
      political issue in the United States, leading to restrictions on how US
      development funding for combatting HIV is allocated. The Alan Guttmacher
      Institute investigated changes that occurred in abstinence, monogamy and condom
      use in Uganda in the 1990s, using nationally representative data from Uganda's
      Demographic and Health Surveys of 1988 (women only), 1995 and 2000 (women and
      men), and national-level findings from two surveys by the Global Programme on
      AIDS in 1989 and 1995 (women and men). Reduction of infection risk by lowering
      numbers or types of partners among people with more than one relationship was not
      covered. Here we reprint the chapter on "Implications" from the AGI report, a
      commentary on the lessons that can and cannot be taken from the data, published
      in a 2003 Guttmacher Report on Public Policy.

PMID- 15242221
TI  - Beyond slogans: lessons from Uganda's experience with ABC and HIV/AIDS.

PMID- 15242222
TI  - Intrauterine contraceptive devices and risk of pelvic inflammatory disease:
      standard of care in high STI prevalence settings.
AB  - The intrauterine contraceptive device (IUD) is highly effective and cost
      effective. IUD use is limited in some regions, however, due to concerns about
      increased risk of pelvic inflammatory disease (PID) and subsequent complications
      such as infertility and ectopic pregnancy. Recent reviews suggest that the
      overall risk of PID with modern IUDs is lower than previously thought, at least
      in regions with a low prevalence of sexually transmitted infections (STIs). Risk
      of PID may be higher, however, in places where gonorrhoea and chlamydia are
      prevalent, where screening for STIs is limited and where aseptic conditions for
      insertion are difficult to ensure. A World Health Organization multi-centre study
      and other studies have confirmed regional differences in STI prevalence, and the
      WHO study established that PID risk is temporally related to IUD insertion
      procedures. Studies of the effectiveness of antibiotic prophylaxis to prevent
      infectious complications are inconclusive due at least in part to use of sub
      therapeutic regimens for pathogens commonly implicated in PID. In summary, the
      IUD can be safe and effective if inserted under aseptic conditions in women free
      of cervical infection. Further study is needed to define appropriate standards of
      care for IUD insertion where STI prevalence is high and ability to rule out
      infection is limited. Even with safe insertion, IUD promotion in areas of high
      STI/HIV prevalence must address women's needs for dual protection from infection
      and unwanted pregnancy.

PMID- 15242223
TI  - Women's autonomy, education and employment in Oman and their influence on
      contraceptive use.
AB  - Since 1970 political and economic changes have brought about great improvements
      in health and education in Oman, and since 1994 the government has provided free
      contraceptives to all married couples in primary health care centres. Despite
      rapid socio-economic development, the fertility rate was 4.2 in 2001. The aim of
      this study was to define baseline data on ever-married women's empowerment in
      Oman from a national study in 2000, analyse the correlates of women's empowerment
      and the effect of empowerment on unmet need for contraception. Two indicators of
      empowerment were used: women's involvement in decision-making and freedom of
      movement. Bivariate analysis was used to link these measures and their proxies,
      education and employment status, with use of a family planning method. Education
      was a key indicator of women's status. Unmet contraceptive need for women exposed
      to pregnancy was nearly 25%, but decreased significantly with educational level
      and paid employment. While empowered women were more likely to use contraception,
      women's education was a better predictor of "met need" than autonomy, as
      traditional factors and community influence remain strong. For nearly half the
      1,830 women in the study, the husband decided whether contraception was used.
      Fewer than 1% were using contraception before their first child as women are
      expected to have a child within the first year of marriage.

PMID- 15242224
TI  - Meeting the contraceptive needs of unmarried young people: attitudes of formal
      and informal sector providers in Vientiane Municipality, Lao PDR.
AB  - In Lao PDR, evidence is emerging of considerable sexual activity among unmarried
      youth, but contraceptive services remain inadequate to meet their needs. This
      study explored the attitudes of formal and informal sector providers in serving
      the contraceptive needs of unmarried youth in Vientiane Municipality, their
      perceptions of quality of care, confidentiality and privacy, level of comfort in
      discussing sexual matters, and any differences between providers in the two
      sectors. In-depth interviews were carried out with 56 key informants, followed by
      a quantitative survey of 150 formal sector and 100 informal sector providers. We
      found ambivalence and discomfort among providers in communicating with unmarried
      youth and providing contraceptives to them, and low priority placed on their
      right to privacy and confidentiality. Providers tended to attribute difficulties
      almost entirely to young people's inhibitions and unwillingness to listen. Less
      than 60% of formal sector providers would supply contraceptives to unmarried
      youth, compared to 80% of informal providers, but the latter were more likely to
      charge a fee for supplies. Both formal and informal sector providers need
      training in communication and counselling skills for serving unmarried youth.
      Programmes must ensure that unmarried youth have access to good quality
      contraceptive services and supplies.

PMID- 15242225
TI  - Listening to "felt needs": investigating genital prolapse in western Nepal.
AB  - The global prevalence of genital prolapse is estimated to be 2-20% in women under
      age 45. In Nepal, genital prolapse appears to be widespread, but little published
      evidence exists to buttress this claim. This paper presents findings of two
      studies, one ethnographic and one clinic-based, in western Nepal. The
      ethnographic study involved 16 focus group discussions with 120 community members
      and key informants, and covered community perceptions and women's experience of
      prolapse and its perceived causes and consequences. The clinic-based study was
      conducted among 2,072 women who presented with gynaecological complaints and
      received a diagnosis. One in four of them had genital prolapse, of whom 95% had
      self-reported the prolapse. The most commonly perceived causes of prolapse were
      lifting heavy loads, including in the post-partum period. The adverse effects
      reported included difficulty urinating, abdominal pain, backache, painful
      intercourse, burning upon urination, white watery discharge, foul-smelling
      discharge, itching, and difficulty lifting, sitting, walking and standing. The
      results confirm prolapse as a significant public health problem in western Nepal.
      We strongly recommend developing systematic, rotational gynaecological clinics in
      rural districts, the use of a screening checklist and counselling for prevention
      and early management of genital prolapse by district health workers for family
      planning and antenatal patients.

PMID- 15242226
TI  - Performance characteristics of aerobic/anoxic sludge digestion at elevated
      temperatures.
AB  - Laboratory experiments were conducted to study the performance of aerobic/anoxic
      digestion of mixed primary and waste activated sludge compared to aerobic
      digestion alone in terms of solids destruction, organic reduction, nutrient
      removal, filtrate quality and sludge dewaterability. The process performance was
      examined at different solids residence times (10 and 20 d), temperatures (20, 30
      and 40 degrees C) and anoxic cycle length (0, 8, 12 and 16 h). Both modes of
      operation gave comparable solids destruction results. The volatile suspended
      solids (VSS) reduction was affected by temperature with the highest VSS reduction
      reported at 30 degrees C (42.4%), while solid retention time (SRT) did not seem
      to affect the process as indicated by the percent VSS removal. Biodegradable
      solids destruction followed a first-order kinetic model. Aerobic/anoxic sludge
      digestion is advantageous to mere aerobic digestion since it improves sludge
      dewaterability and filtrate quality. Alternating aerobic/anoxic operation can
      conserve most of the influent alkalinity and maintain near neutral pH conditions
      over prolonged periods. Optimum process performance was observed at 20 degrees C
      with SRT of 10 days and anoxic cycle length of 8 hours.

PMID- 15242227
TI  - Optimisation of process parameters for adsorption of metal ions on straw carbon
      by using response surface methodology.
AB  - Optimisation of process parameters for adsorption of metal ions viz., Cu2+, Cd2+
      and Ni2+ ions on Straw Carbon (SC) was carried out by using Box-Behnken
      statistics and analysis of variance methods. Response surface methodology with
      three levels of initial pH (4, 5, 6), dose (8, 10, 12 gl(-1)) and particle size
      (0.075, 0.090, 0.106m micron) were used in the identification of significance of
      the effects and interactions in adsorption studies. Response surface methodology
      requires no assumption and identifies the principal experimental variables and
      their interactions which have the greatest effect on adsorption. The optimum
      process parameters for maximum adsorption of Ni2+, Cu2+ and Cd2+ were obtained by
      this procedure.

PMID- 15242228
TI  - Upgrading of existing sludge treatment processes for phosphorus management
      serving a EBPR WWTP.
AB  - For a large-scale wastewater treatment plant to comply with phosphorus consents
      using enhanced biological phosphorus removal processes, its sludge and liquor
      treatment processes need to be carefully upgraded. In this case study, the
      wastewater treatment plant of interest has three different types of sludge
      treated by two different and independent sludge treatment processes. The task of
      upgrading the sludge treatment systems to serve an EBPR process while satisfying
      other regulatory and operational constraints in a cost effective way presents an
      interesting challenge. A range of process options was investigated to include P
      rich surplus activated sludge treatment, raw sludge treatment, and sludge liquors
      treatment. Sludge pre-liming, i.e. to introduce lime slurry into raw liquid
      sludge before the dewatering stage, was studied in bench-scale and full-scale
      trials for phosphorus precipitation and pathogen reduction. It was applied to the
      mixture of surplus activated sludge and imported sludge. The results showed that
      a complete phosphorus precipitation was achieved at above pH 9 with lime addition
      of 7% (w/w as calcium hydroxide to sludge dry weight). A satisfactory 2-log
      pathogen reduction was consistently achieved at above pH 11 with lime addition of
      14% (w/w). The process significantly simplified the potential upgrading work for
      sludge and liquor treatment, compared to other alternatives.

PMID- 15242229
TI  - A pilot study on phosphate and nitrate removal from secondary wastewater effluent
      using a selective ion exchange process.
AB  - A pilot study was conducted at a wastewater treatment plant (WWTP) in Easton,
      Pennsylvania, for the removal of varying concentrations of phosphate (HPO4(2-))
      and nitrate NO3- using a newly developed ion exchange material referred to as
      Polymeric Ligand Exchanger (PLE). The PLE was prepared by immobilizing copper
      (II) ions onto a commercially available chelating resin, DOW-3N. The loaded
      copper ions act as ligand exchanger sites that selectively bind with target
      ligands such as phosphate and nitrate. This pilot study was the final
      experimental testing phase of the PLE toward the full process development for the
      selective removal of both phosphate and nitrate using secondary effluent from a
      fully operational WWTP. In order to establish the effectiveness of the PLE, a
      commercially available activated alumina (AA) was also tested for comparison.
      Effluent phosphorus and nitrate concentration of less than 0.1 mg l(-1) were
      achieved for up to 500 bed volumes; phosphorous was reduced from an average
      concentration of 4.0 mg l(-1) and nitrate from average concentration of 16.4 mg
      l(-1). In accord with prior laboratory observations, the pilot test results
      showed that the PLE could selectively remove phosphate from secondary municipal
      wastewater effluent under normal conditions (pH, ionic strength, dissolved
      organic carbon content). In addition, the pilot study provided new evidence that
      nitrate could be removed from secondary municipal wastewater effluent and
      concurrently with phosphate. The selective ion exchange process provides an
      alternative for concurrent removal of the eutrophic-enhancing nutrients,
      phosphate and nitrate.

PMID- 15242230
TI  - Treatment of hypersaline industrial wastewater by a microbial consortium in a
      sequencing batch reactor.
AB  - Hypersaline effluents are produced by various industrial activities. Such
      wastewater, rich in both organic matter and salt (> 35 g l(-1)), is difficult to
      treat by conventional wastewater treatment processes. It is necessary to use
      halophilic bacteria. In this study, a bench-scale sequencing batch reactor (SBR)
      was inoculated with halophilic sediments in order to treat an agri-food effluent
      containing 120 g salt l(-1). The micro-organisms were able to treat carbon and
      nitrogen, provided the pH in the reactor was neutralised with phosphoric acid.
      Soluble COD and Soluble TKN removal attained 83% and 72% respectively. 16S rDNA
      identification of the halophilic microbial community showed high diversity.

PMID- 15242231
TI  - Common effluent treatment plant (CETP) for wastewater management from a cluster
      of small scale tanneries.
AB  - Effluent treatment plants need land for construction, capital cost, power and
      specialized manpower for their operation and maintenance. Because of these
      constraints, small scale tanneries can not afford to have their own effluent
      treatment facilities and therefore, combined effluent from all tanneries are to
      be brought to a centralized place for treatment. This facility is called a Common
      Effluent Treatment Plant (CETP). For operation and maintenance of CETP, small
      scale tanners formed a co-operative society. The expenses for operation and
      maintenance of CETP are being shared by participating tanneries. Wastewater
      management for the cluster of small scale tanneries was studied in details and
      various measures were incorporated to improve performance of the CETP and also to
      improve treated effluent quality to confirm standard prescribed by regulatory
      agencies. Performance of existing CETP was evaluated. Based on the results, bench
      scale laboratory treatability studies were conducted for improvement in treated
      effluent quality and also to suggest appropriate modifications to the CETP. These
      studies are detailed in this paper.

PMID- 15242232
TI  - Evaluation of a laboratory and full-scale microalgae pond for tertiary treatment
      of piggery wastes.
AB  - Piggery wastes tertiary treatment in laboratory and full-scale microalgal ponds
      was evaluated. COD, BOD, inorganic nitrogen and orthophosphate removals of up to
      57%, 69%, 79% and 74%, respectively, were obtained. The effect of the hydraulic
      retention time (HRT) on removal efficiencies followed an exponential
      relationship. COD, BOD and orthophosphate removal rate decreased with increased
      effluent concentration while the inorganic nitrogen removal rate increased with
      an increasing effluent substrate concentration at inorganic nitrogen
      concentration values lower than 0.07 g l(-1). Values of maximum substrate removal
      rate, half rate constant, cell yield coefficient, endogenous constant and maximum
      specific growth rate were 7.1 +/- 0.5 d(-1), 0.21 +/- 0.02 g l(-1), 0.26 +/- 0.01
      g VSS g(-1) COD, 0.012 +/- 0.001 d(-1)and 1.9 +/- 0.9 d(-1), respectively. At
      full-scale, effluent COD, BOD, MPN, inorganic nitrogen and orthophosphate
      decreased while pH and Chlorophyll a increased with the operation time. It was
      found that the use of the final effluent as drinking water did not affect pigs
      growth.

PMID- 15242233
TI  - The treatability study of high strength pet food wastewater: a continuous flow
      aerobic system performance evaluation.
AB  - This paper presents continuous flow two stage activated sludge treatability
      studies for the treatment of pet food wastewaters characterized by oil & grease
      concentration of 50,000-66,000 mg l(-1), total COD & BOD concentrations of
      100,000 mg l(-1) and 80,000 mg l(-1), respectively. A pre-treatment system,
      dissolved air flotation (DAF) achieved 97-99% reduction in oil and grease down to
      about 400-800 mg l(-1). The pilot experimental results showed that for the DAF
      pretreated effluent, 97% soluble COD removal efficiency can be achieved by using
      two stage conventional activated sludge system at a 6-7 days HRT and applied
      initial soluble COD to biomass ratio of 1.17 mg COD mg VSS. Meanwhile, the system
      achieved 99.9% soluble BOD removal. Analysis of system kinetics indicated that
      this particular wastewater is very difficult to biodegrade, with an extremely
      high half velocity constant "Ks" of 5800 mg l(-1). The research showed the
      potential applications of activated sludge systems for the treatment of high oil
      and grease wastewater.

PMID- 15242234
TI  - [Metal logarithmic scale titration as a tool for complexing ligand distribution
      determination: an application by DPASV].
AB  - A new logarithmic scale titration is proposed for the characterisation of natural
      organic matter-trace metals interactions in natural systems. The Suwannee River
      Fulvic Acid complexation with Cd and Pb ions has been analysed by this technique,
      using Differential Pulse Anodic Stripping Voltammetry (DPASV) for labile metal
      concentrations measurement. Results of titrations have been modelled by four
      ligands. Their complexing properties (CLi, Ki(Cd), Ki(Pb)) have been determined
      by a non-linear optimisation based on the speciation program MINEQL, coupled with
      a simplex. These ligands were called "very weak, weak, strong and very strong"
      with respect to their complexing constants (Ki(Cd), Ki(Pb)) ranging from 10(4) to
      10(11). The obtained ligands concentrations (CLi) are respectively 1.9 microM,
      150 nM, 25.1 nM and 21.1 nM for a 7.9 ppm carbon content. Moreover, this model
      takes account of the pH dependency and metals competition respectively by
      experiments at pH 7.8 and 4.6, and by definition of stability constants for each
      ligand toward each analysed metal. As a conclusion, the authors suggest a
      systematic use of the logarithmic scale titrations when full characterisation of
      the metal-organic matter interactions is necessary.

PMID- 15242235
TI  - Fenton oxidation of Reactive Black 5: effect of mixing intensity and reagent
      addition strategy.
AB  - This study investigates the effect of mixing intensity and reagents addition
      strategy on Fenton's reagent degrading a common reactive diazo type dyestuff,
      Reactive Black 5. Within the experimental conditions used in the study, the
      effect of mixing intensity on TOC removal was observed to be both significant and
      complex. Using factorial analysis, it was found that if the reagents are added
      near to each other, higher mixing intensity will enhance the effectiveness of the
      degradation process. However, a very, high mixing level may cause reduction in
      performance. It was also observed that the mixing intensity effect interacts with
      Fe2+ or/and H2O2 dosage. The benefit of increasing mixing intensity appears to be
      higher for lower reagents dosage. The effect of reagents addition strategy was
      found to be inter-dependent with mixing intensity level. It was also deduced that
      proper chemical addition strategy could be used to reduce the mixing intensity
      requirement of the process.

PMID- 15242236
TI  - Stimulation of methanogenesis in a laboratory scale UASB reactor treating
      domestic sewage by Fe(0) application.
AB  - The effects of application of zero valence Fe (Fe(0)) on the anaerobic digestion
      of sewage was investigated using two laboratory scale UASB reactors. One reactor
      had Fe(0) addition in a container found midway along the recycling loop. The
      other one was a control reactor. In a test run period of 76 days, the Fe(0)
      application significantly increased the CH, yield by 8.7% and decreased the
      effluent COD concentration by 21.0% relative to the control reactor. A decrease
      of the H, concentration of biogas and the CODs/CODt ratio in effluent by Fe(0)
      application were observed. The obtained results imply that the methanogenesis and
      COD removal efficiency of the UASB reactor were stimulated by Fe(0) application.
      The higher performance of the reactor with Fe(0) application arises from the
      integrated functions of Fe(0) or its ionic state as donor of H2, macronutrient,
      and flocculant. This study showed that the supply of Fe(0) to a UASB can improve
      the methanogenesis and the overall COD removal of a UASB reactor treating low
      strength domestic waste water.

PMID- 15242237
TI  - Is Atkins dead (again)?
AB  - Despite consistent epidemiological evidence that weight gain is linked to higher
      fat and lower carbohydrate consumption, supported by animal evidence and the
      inescapable truth that fat supplies 9 kcal/g compared to 3.75 kcal/g from
      carbohydrates, low-carbohydrate "Atkins" style diets are heavily promoted for
      obesity control. The randomised controlled trial evidence is very small. The
      totality of the evidence continues to show that low-carbohydrate diets are
      marginally disadvantageous for long-term health and for weight maintenance.
      People can lose weight equally well on low-carbohydrate ("Atkins-style") diets,
      and some groups of obese patients tend to lose a little more than on high
      carbohydrate groups. This small difference (1-2 kg) may be explained by rapid
      loss of (glycogen-associated) body water, or by the influence of extraordinary
      media coverage leading to elevation of expectation and compliance with low
      carbohydrate diets in the short term.

PMID- 15242239
TI  - A new approach to the quantitative measurement of dense LDL subfractions.
AB  - OBJECTIVES: Small dense low-density lipoproteins (LDLs) should be considered a
      major risk factor for cardiovascular disease, but there is still no recommended
      method for measuring them or expressing clinical values. We measured the dense
      LDL portion relatively simply by isolating it using density ultracentrifugation
      and then giving it a relative, quantitative value. DESIGN AND METHODS: Dense LDLs
      (d=1.048-1.063 g/mL) were isolated from human plasma at the same time as total
      LDL (d=1.021-1.063 g/mL) by means of sequential ultracentrifugation, and the
      former was assessed as a percentage of the latter. A receiver operator
      characteristic (ROC) curve was used to compare the different LDL components as
      markers of dense LDLs. The proposed method was compared with non-denaturing
      gradient gel electrophoresis (NDGGE). In order to obtain clinical data, the dense
      LDL portion was measured in diabetic and postmenopausal subjects and healthy
      controls. RESULTS: The ROC curve showed that cholesterol level was a more
      accurate marker of dense LDLs. The within-run precision (CV) was 2.28%, and the
      between-run CV was 5.1%. Analytical recovery was 80.2+/-1.6%. The correlation
      between the proposed method and NDGGE was r=0.90, p<0.001. The dense LDL
      percentage significantly correlated with serum triglyceride (r=0.57, p<0.001) and
      high-density lipoprotein cholesterol levels (r=-0.33, p<0.01), but not with the
      LDL-cholesterol/apolipoprotein B ratio. The diabetic patients and postmenopausal
      women had higher dense LDL values than the healthy controls. CONCLUSIONS: The
      results obtained using this procedure are in line with those obtained using
      NDGGE, which is the conventional assay system for measuring LDL size. Determining
      the small dense LDL portion by means of its cholesterol content may be a better
      approach to characterising the risk of cardiovascular disease, even in the
      presence of relatively normal LDL-cholesterol levels.

PMID- 15242238
TI  - Body fat and C-reactive protein levels in healthy non-obese men.
AB  - BACKGROUND AND AIM: The relationships between C-reactive protein (CRP) levels,
      adipose tissue and metabolic alterations have not been clearly established in
      healthy non-obese subjects. We investigated the relationships between body fat,
      CRP levels and metabolic variables in healthy, non-obese sons of patients
      affected by metabolic syndrome (MS). METHODS AND RESULTS: Age, CRP and
      interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist
      circumference and waist-to-hip ratio, WHR), total and regional fat content (as
      determined by means of dual X-ray absorptiometry, DXA), total and LDL
      cholesterol, and the metabolic variables related to MS (HDL-cholesterol,
      triglyceride, glucose and insulin levels; the fasting insulin resistance index,
      FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients.
      Linear and multiple regression analyses were used to evaluate the relationships
      between body fat, metabolic variables and CRP levels, and to investigate whether
      the association between body fat content and metabolic variables persists after
      adjustment for CRP levels. Body fat was associated with all of the investigated
      variables. CRP levels were associated with total and regional body fat, the
      anthropometric index of weight, age, and with some metabolic alterations (HDL
      cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin
      and LDL-cholesterol levels). The associations between total body fat and the
      metabolic variables did not change after adjustment for CRP levels. Total body
      fat was the best predictor of CRP levels (p<0.0001). CONCLUSIONS: In healthy, non
      obese sons of MS patients, total body fat is the best predictor of CRP levels,
      and remains closely associated with metabolic abnormalities after adjustment for
      CRP levels. These findings strongly support the hypothesis that body fat is the
      main determinant of metabolic abnormalities and a low inflammatory state, at
      least in healthy subjects.

PMID- 15242240
TI  - Associations between HDL oxidation and paraoxonase-1 and paraoxonase-1 gene
      polymorphisms in families affected by familial combined hyperlipidemia.
AB  - BACKGROUND AND AIM: It has been shown in vitro that the HDL-bound enzyme
      paraoxonase-1 (PON1) protects LDL against oxidation, and PON1 and PON1 gene
      polymorphisms may affect the oxidation of HDL particles. The aim of this study
      was to investigate the associations between in vitro HDL oxidation parameters,
      endogenous PON1 and PON1 genotypes in families affected by asymptomatic FCHL.
      METHODS AND RESULTS: Serum arylesterase (ARE) and PON1 activities, PON1 mass,
      PON1 genotypes and the kinetics of CuSO4-induced HDL oxidation in vitro were
      measured in 150 members of FCHL families free of clinical CAD. At univariate
      analysis, log PON1/apoA-I and the PON1 mass/apoA-I ratio significantly correlated
      with lag time, maximum diene formation and the propagation rate. The oxidation
      parameters also correlated with PON1 genotypes. Multivariate analysis showed that
      the associations between PON1 mass/unit apoA-I and the oxidation parameters were
      independent of the other variables. The lag time of HDL oxidation was also
      associated with the PON1 genotype 192QR. CONCLUSIONS: Endogenous PON1 may have
      protective effects on the different stages of HDL oxidation in the members of
      families affected by FCHL. This protective effect is independent of other
      biochemical factors, but may be influenced by the PON1 gene polymorphism. The
      endogenous PON1 content of HDL seems to be an important determinant of the anti
      atherogenicity of this lipoprotein.

PMID- 15242241
TI  - The role of the renin angiotensin hormonal system in the metabolic syndrome and
      type 2 diabetes.
AB  - Potentially important new findings have recently been reported concerning the so
      called metabolic syndrome in relation to the renin-angiotensin system, ie, that
      treatment with inhibitors of the angiotensin-converting enzyme (ACE) not only
      decreases blood pressure levels but prevents the development of diabetes
      mellitus. The new findings described in this article highlight the potential role
      of the ACE system in the regulation of insulin sensitivity, thus contributing to
      the development of type 2 diabetes and metabolic syndrome. In addition to the
      well known selective effects of ACE inhibitors and angiotensin II receptor
      blockers in reducing microalbuminuria in diabetic patients, the potential ability
      of these drugs to reduce the risk of diabetes and the metabolic syndrome would
      support their use as first line agents not only in diabetic patients but also in
      selected groups of hypertensive patients, who are particularly at risk of
      developing metabolic complications. This information supports the Joint
      Guidelines for the Management of Arterial Hypertension by the European Society of
      Hypertension and the European Society of Cardiology, which highlight the crucial
      role of ACE inhibitors and the angiotensin II receptor blockers in preventing the
      development of diabetes in hypertensive patients.

PMID- 15242242
TI  - Lipid components and fatty acid composition of Iraqi subjects who smoke and
      consume dairy products.

PMID- 15242244
TI  - Nutritional recommendations for the prevention of ischemic stroke.

PMID- 15242243
TI  - Nutrition and prevention of ischemic stroke: present knowledge, limitations and
      future perspectives.
AB  - Stroke, particularly ischemic stroke, has a major impact on public health due to
      its high incidence, prevalence and rate of subsequent disability in Italy as in
      most industrialised countries. Apart from age, many modifiable factors, such as
      hypertension, smoking, diabetes, dyslipidemia, obesity, physical inactivity,
      alcohol abuse and hyperhomocysteinemia, have been recognised as playing a role in
      the pathogenesis of this disease. While appropriate pharmacological therapy has
      proven effective in the prevention of stroke in particular categories of
      patients, most of the above mentioned predisposing conditions are amenable to be
      affected by nutrition. Unequivocal demonstration of a protective or adverse role
      of single foods and nutrients against the risk of stroke has been however
      difficult to achieve due to confounding by biological variability, methodological
      inadequacies in the assessment of individual nutritional habits and difficulty to
      carry out long-term randomised controlled trials in the nutritional area.
      Notwithstanding, in several cases, causal relationships could be inferred from
      case-control and cohort studies in the presence of plausible and reproducible
      associations, evidence of dose-dependent effects and consistency in the results
      of different studies. The aim of this paper was to review present knowledge and
      highlight limitations and future perspectives about the role of nutrition in the
      prevention of ischemic stroke.

PMID- 15242245
TI  - Development of novel alkylating drugs as anticancer agents.
AB  - Although conventional alkylating drugs have proven efficacy in the treatment of
      malignancies, the agents themselves are not selective. Therefore, non-specific
      alkylation of cellular nucleophilic targets may contribute to many of the
      observed toxic effects. Novel approaches to drug discovery have resulted in
      candidate agents that are focused on 'soft alkylation'--alkylators with greater
      target selectivity. This review highlights the discovery of small molecule drugs
      that bind to DNA with higher selectivity, act in a unique hypoxic tumor
      environment, or covalently bind specific protein targets overexpressed in cancer,
      such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone
      deacetylase.

PMID- 15242246
TI  - Purine nucleoside antimetabolites in development for the treatment of cancer.
AB  - Purine nucleoside analogs are an important class of drugs that are used in the
      treatment of cancer. Five purine analogs have been approved by the FDA
      (mercaptopurine, thioguanine, fludarabine monophosphate, deoxycoformycin and
      cladribine) and four compounds are currently being evaluated clinically
      (clofarabine, immucillin-H, nelarabine and 8-chloroadenosine). In addition, two
      gene therapy approaches are being evaluated that are based on the selective
      activation of purine nucleoside analogs (ganciclovir, fludarabine monophosphate
      and others) in tumor cells. Even though nucleoside analogs have been extensively
      evaluated over the last 50 years, the development of these new compounds
      demonstrates that there is still much promise in identifying new anticancer drugs
      from this class of compounds.

PMID- 15242247
TI  - Receptor tyrosine kinase inhibitors as anti-angiogenic agents.
AB  - Receptor tyrosine kinases (RTKs) and their ligands have been implicated in
      angiogenesis and current data suggest that they are potential cancer therapeutic
      targets. Split-kinase domain RTKs, including receptors for vascular endothelial
      growth factor receptor, platelet-derived growth factor and fibroblast growth
      factor, have important roles in tumor angiogenesis. RTK inhibitors targeting
      tumor microvasculature have shown promising results in preclinical studies, and
      use of these compounds as single agents, or in combination with other cytotoxic
      therapies, including radiation, is an area of active clinical investigation.
      Preclinical and clinical data from representative anti-angiogenic RTK inhibitors
      will be discussed in this review.

PMID- 15242248
TI  - Aromatase inhibitors for hormonal therapy of early-stage breast cancer.
AB  - Aromatase inhibitors block estrogen synthesis by inhibiting aromatase, the enzyme
      responsible for the conversion of adrenal steroids to estrogen. They are approved
      for the first-line treatment of metastatic breast cancer in hormone receptor
      positive women. Three large, well-designed randomized trials have been reported
      which support the use of aromatase inhibitors in the treatment of early stage
      breast cancer. This review focuses on data on aromatase inhibitors in the
      adjuvant setting and looks to the future potential of these drugs in both ductal
      carcinoma in situ and chemoprevention.

PMID- 15242249
TI  - Monoclonal antibodies and prostate-specific membrane antigen.
AB  - Efforts are increasing to identify and evaluate diagnostic and therapeutic
      markers for prostate cancer patients. One of these, prostate-specific membrane
      antigen (PSMA), a transmembrane protein highly expressed in all types of
      prostatic tissue (eg, benign epithelium, benign prostatic hyperplasia, prostatic
      intra-epithelial neoplasia and adenocarcinomas, with increased binding affinity
      for malignant cells), is becoming an increasingly important diagnostic and
      therapeutic marker, not only for prostate cancer, but possibly for other
      malignant lesions. Recent studies have demonstrated PSMA expression in
      endothelial cells of tumor-associated neovasculature (including carcinoma of the
      colon, breast, bladder, pancreas, kidney and melanoma), thus greatly expanding
      its possible beneficial role, especially as new anti-PSMA mAbs continue to be
      developed and refined. Future diagnostic and therapeutic interventions utilizing
      these antibodies will become increasingly important in not only prostate cancer
      but perhaps many other different malignancy types.

PMID- 15242250
TI  - Drug-induced destabilization of bcl-2 mRNA: a new approach for inducing apoptosis
      in tumor cells.
AB  - Recent evidence suggests that the 3' untranslated region (3' UTR) of some mRNAs
      is a molecular hotspot for pathology. The 3' UTR of bcl-2 mRNA contains several
      AU-rich elements (AREs) that promote mRNA destabilization. Recent studies have
      demonstrated that the protein, nucleolin, binds to an ARE in bcl-2 mRNA, thereby
      protecting this mRNA from nuclease degradation. All-trans retinoic acid, taxol
      and okadiac acid induce downregulation or inactivation of nucleolin, which
      destabilizes bcl-2 mRNA and triggers apoptosis. The ARE instability elements in
      bcl-2 mRNA are potential therapeutic targets for inducing apoptosis and
      overcoming drug resistance in cancer cells.

PMID- 15242251
TI  - Therapeutic impact of methoxyamine: blocking repair of abasic sites in the base
      excision repair pathway.
AB  - A major obstacle to effective treatment with alkylating agents in cancer is the
      presence of elaborate mechanisms of DNA repair. For instance, the methylating
      therapeutic agent, temozolomide forms O6-methylguanine (O6mG), 7-methylguanine
      (N7mG) and 3-methyladenine (N3mA) DNA adducts that are repaired by at least two
      mechanisms. The O6mG DNA adduct, a cytotoxic and genotoxic lesion, is repaired by
      O6-methylguanine DNA-methyltransferase (MGMT). Thus, MGMT is a major mechanism of
      resistance to methylating agents. Meanwhile, cell death caused by O6mG adducts is
      promoted by mismatch repair (MMR) system, such that deficiency in MMR is
      associated with pronounced resistance to methylating agents. N7mG, the dominant
      lesions formed by methylating therapeutic agents, and N3mA DNA adducts are
      removed by the base excision repair (BER) pathway. Efficient BER repair minimizes
      the impact of these lesions in normal and tumor cells. Thus, only when BER is
      disrupted, do these abundant N-methylated DNA adducts become highly cytotoxic.
      Most importantly, BER disruption is able to bypass other resistance factors such
      as MMR defects and high MGMT activity. BER, in fact, is an important drug
      resistant factor because of its variety of substrates and the ability to rapidly
      and efficiently repair these DNA lesions. However, the impact of both active BER
      and inactive BER on anticancer therapy has yet to be fully studied. This review
      will establish the premise that targeting abasic sites formed during BER will
      disrupt this pathway and enhance the therapeutic efficacy of alkylating agents.

PMID- 15242252
TI  - AN-9 (Titan).
AB  - Titan is developing AN-9 for the potential treatment of various cancers. AN-9 is
      a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of
      cancer cells through signaling cellular differentiation. In March 2001, a phase
      I/II study involving patients with liver tumors was initiated. By November 2001,
      enrollment had been completed in a second phase II study of refractory non-small
      cell lung cancer (NSCLC). In June 2003, Titan began enrollment for a phase IIb
      trial of AN-9 in combination with docetaxel in patients with NSCLC.

PMID- 15242253
TI  - CC-5013 (Celgene).
AB  - Celgene, in collaboration with the National Cancer Institute, is developing CC
      5013, the lead compound in a series of thalidomide derivatives that inhibit
      TNFalpha overproduction, for the potential treatment of hematological and solid
      tumor cancers and inflammatory diseases.

PMID- 15242254
TI  - OSI-461 (OSI).
AB  - OSI Pharmaceuticals is developing OSI-461, a potent analog of exisulind, for the
      potential treatment of cancer and inflammatory bowel disease. In August 2001, OSI
      461 entered phase II trials involving patients with chronic lymphocytic leukemia.
      In July 2002, the company embarked on a pilot phase II study evaluating OSI-461
      for the treatment of Crohn's disease. By October 2002, Cell Pathways had selected
      hormone-refractory prostate cancer as the lead cancer indication for clinical
      development of OSI-461.

PMID- 15242255
TI  - Epothilone D (Kosan/Roche).
AB  - Kosan and Roche are developing the microtubule inhibitor epothilone D (KOS-862
      and NSC-703147), an analog of epothilone B for the potential treatment of cancer.
      Phase II trials in colorectal, metastatic breast and non-small-cell lung cancers
      were initiated in December 2003.

PMID- 15242256
TI  - AE-941 (AEterna).
AB  - AEterna is developing AE-941, an angiogenesis inhibitor derived from the
      ultrafiltration of liquid shark cartilage, with matrix metalloprotease (MMP)-2,
      MMP-9 and vascular endothelial growth factor inhibitory properties, for the
      potential treatment of non-small-cell lung cancer.

PMID- 15242257
TI  - 'F' words.

PMID- 15242258
TI  - Clinical considerations for adhesive bridgework.
AB  - Many dental practitioners do not use adhesive bridges because of concerns over
      high failure rates. Techniques for these restorations should be based on the
      fundamental principles of bridge design which require rigid, accurately fitting
      frameworks and careful control of the occlusion. The abutments generally require
      little if any tooth preparation. Greater security will result from more extensive
      coverage of abutment teeth: the routine use of relative axial tooth movement is a
      predictable method for creating the space that this approach requires.

PMID- 15242259
TI  - Digital imaging for the general dental practitioner: 1. Getting started.
AB  - Clinical photography has been used in dental practices all over the world for
      many years, although it has generally been the keen amateur photographer or
      enthusiastic practitioner who undertook clinical photography, often with
      specialized equipment. Understanding the equipment, and how to use it
      successfully, have caused many hours of frustration, culminating in an anxious
      wait for the results to be returned (or lost) by the processors.

PMID- 15242260
TI  - Alzheimer's disease and oral care.
AB  - Alzheimer's disease (AD) is the commonest form of dementia, closely associated
      with age, but also with other causative factors. AD affects half a million people
      in the UK, and presents dentists with numerous behavioural and clinical
      challenges. The aetiology, diagnosis and medical treatment for persons with AD
      are discussed, together with communication strategies and issues related to
      families and care-givers. Realistic dental treatment planning for patients in
      early, moderate and late stage AD is considered in conjunction with relevant
      ethical issues. Dentists have the potential to improve markedly the quality of
      life for people with AD.

PMID- 15242261
TI  - Reflective practice and experiential learning: tools for continuing professional
      development.
AB  - The models of reflective practice and experiential learning, described within
      this article, provide the dental practitioner and his/her team with realistic
      methods by which they can improve their skills and working atmosphere, and also
      reduce occupational stress. The reflective dentist is one who engages his/her
      team in a process of discussion regarding a variety of clinical situations, and
      who learns from both positive and negative clinical experience. This article
      offers a detailed analysis of reflective practice and experiential learning, and
      the ways in which application of these procedures can contribute significantly to
      the continuing professional development of dentists and dental teams.

PMID- 15242263
TI  - Oral tonsils (ectopic oral tonsillar tissue).
AB  - Oral tonsils (ectopic oral tonsillar tissue) are rarely remarked upon. They may
      cause diagnostic confusion, especially when found in the floor of the mouth. We
      report here two cases of patients presenting because of oral tonsillar tissue, to
      remind colleagues of its occurrence and the need to consider the lesion in the
      differential diagnosis of soft tissue nodules of the oral cavity.

PMID- 15242262
TI  - The use of osseointegrated implants in orthodontic patients: I. Implants and
      their use in children.
AB  - Implants have been used successfully for the rehabilitation of edentulous adults.
      However, their use in children is limited because of the special problems of
      implants relating to continuing growth and development. This, the first of two
      articles, provides a review of the use of osseointegrated implants in the context
      of facial growth, and the role of the orthodontist in the management of implant
      supported prosthodontic structures. A second article will discuss the role of
      implants in orthodontics in providing what has been termed 'absolute anchorage'.

PMID- 15242264
TI  - ART: a minimal intervention approach to manage dental caries.
AB  - The number of studies investigating aspects of the Atraumatic Restorative
      Treatment (ART) approach has increased in recent years. This tissue preservative
      treatment approach appears to be less painful and is, therefore, more patient
      friendly than conventional caries treatments. The investigations so far have
      shown that the ART approach is effective for the management of single-surface
      cavities in both deciduous and permanent dentitions. There appears to be no
      difference in survival results between single-surface ART restorations and
      comparable amalgam restorations in the permanent dentition after three years. The
      surface wear of ART restorations using high-viscosity glass-ionomers after two
      years is low. ART sealants using high-viscosity glass-ionomers are retained
      longer than ART sealants using low-viscosity glass-ionomers after three years. It
      is concluded that the ART approach is beneficial in improving the oral health of
      many, not only in developing but also in more advanced countries.

PMID- 15242265
TI  - An aid to the management of xerostomia in the partially dentate patient.
AB  - Xerostomia is becoming more frequently encountered, often in relation to the use
      of pharmacological agents. This paper describes the management of a patient with
      xerostomia, both in terms of her dry mucosa and the difficulties in constructing
      new dentures.

PMID- 15242266
TI  - Use of operating telescopes with multifocal corrective lenses.
AB  - Many older practitioners who wear spectacles with multifocal lenses for surgery
      work have been told that they cannot use flip-up magnifying telescopes with these
      owing to the difficulty of positioning them over the appropriate part of the lens
      and therefore must resort to normal bifocals. They thereby lose the advantages of
      clear vision at all distances which multifocals give. This article describes a
      way of overcoming this problem.

PMID- 15242267
TI  - Physical signs for the general dental practitioner. Case 15. Parotid swelling.

PMID- 15242268
TI  - Progress towards sustainable measles mortality reduction--South-East Asia region,
      1999-2002.

PMID- 15242269
TI  - Oxidative stress and anti-oxidant status in leprosy patients.
AB  - Severe oxidative stress has been reported in leprosy patients because of
      malnutrition and poor immunity. The purpose of this study was to investigate the
      serum lipid peroxidation products, serum LDH and important free radical
      scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti
      oxidant glutathione levels and total anti-oxidant status, in different types of
      leprosy patients. The subjects for this study were normal human volunteers (NHVs,
      n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1,
      n=18), MB patients under treatment (MB2, n=19), and MB patients released from
      treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product,
      malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2,
      MB3) patients, and both gradually decreased with clinical improvement following
      MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant
      status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in
      comparison with NHVs. They gradually increased with clinical improvement with
      MDT. There was no significant variation of these parameters in PB leprosy
      patients in comparison with healthy volunteers. High free radical activity and
      low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate
      that there is an oxidative stress in MB cases, irrespective of the treatment
      status and suggest a suitable anti-oxidant therapy to prevent possible tissue
      injury.

PMID- 15242270
TI  - Modular teaching programme on leprosy.
AB  - Though repeated attention has been drawn to a lack of proper teaching-learning
      modules in leprosy endemic countries, no satisfactory module exists. Keeping in
      view this fact, we attempted to draft a suitable module on leprosy that could be
      used to teach leprosy to undergraduate medical students in a simple and
      comprehensive manner. We used two different modules, Module A and Module B, to
      teach two different batches of students of the pre-final year (VI and VII
      semesters) of the MBBS course. Both these modules were conducted by the
      Department of Dermatology and STD, with participation by the Departments of
      Microbiology, Pathology and Preventive and Social Medicine. The drafts of the
      modules were discussed before hand in the Department, keeping in mind the number
      of days allotted to us. Both the modules were different in certain aspects, but
      the basic concept was the same. Because Module A had more time, certain practical
      aspects were also discussed. It was interesting to note that the percentage of
      increase in the post-test score was 17 for Module A and 15 for Module B, thus
      proving that both the modules were effective in conveying the core message about
      leprosy.

PMID- 15242271
TI  - Palmaris longus--a muscle with multiple uses in leprosy-affected hands.
AB  - The present paper reviews the anatomy of palmaris longus muscle and also the
      situations where palmaris longus muscle has been used as an independent motor or
      as a donor of tendon graft material. Its relevance in leprosy-affected hands is
      also discussed because the muscle is usually spared in hand palsies consequent to
      leprotic neural damage. The advantages and disadvantages of its use in different
      operative procedures have been analyzed. The author's experience with this muscle
      in the correction of hand deformities in leprosy is described.

PMID- 15242272
TI  - Leprosy situation in endemic states of India and prospects of elimination of the
      disease.
AB  - In India there is a dramatic fall in the prevalence rate (PR) of leprosy, but the
      new case-detection rate (NCDR) has not been reduced concomitantly. It is the
      operational efficiency of the National Leprosy Eradication Programme (NLEP) that
      has led to a significant reduction in the NCDR in Andhra Pradesh and Tamil Nadu.
      The ratio of PR to NCDR has been declining in these two states and it reveals
      that elimination could be reached even with the high NCDR level of 3 to 4 per
      10000 population, particularly if single skin lesion (SSL) cases are discharged
      through single dose treatment of rifampicin, ofloxacin and minocycline (ROM). On
      the other hand, the significant number of cases detected in Bihar and Orissa
      during modified leprosy elimination campaigns (MLECs) reveals that there are
      lacunae in operational activities in new case-detection resulting in a large
      number of undetected cases in the community. Only one-third of the cases are
      reporting voluntarily. Awareness of leprosy is not adequate to motivate the
      patients to report voluntarily and complete their treatment, thus underscoring
      the need for relying on active case-detection so that transmission can be broken
      and elimination of leprosy achieved. In addition, the influence of socio-economic
      factors on continued occurrence of leprosy cannot be ruled out. The establishment
      of a sentinel surveillance system along with a computerized simplified
      information system to gain in-depth knowledge on the functioning of the NLEP will
      ensure operational efficiency. In view of this situation, the NLEP should adopt a
      more realistic approach towards reaching the elimination goal.

PMID- 15242273
TI  - Impact of integration of NLEP into PHC system in Madurai district, Tamil Nadu,
      and status of integration of leprosy patients into the community.
AB  - Based on the encouraging results of the integration in Tamil Nadu, the Government
      of India introduced integration in the entire country. In this study on
      integration, Madurai district was taken as the study area. The impact of
      integration on essential indicators of leprosy elimination was analyzed and the
      results are discussed so that they will be useful to other states that are still
      considering integration.

PMID- 15242274
TI  - Leprosy in HIV infection: a study of three cases.
AB  - The course of leprosy in patients with HIV infection has been a controversial
      issue for a long time. It is still a matter of debate whether the HIV status of
      an individual has any impact on the natural history of leprosy and response to
      anti-leprosy treatment. We report here three HIV-positive leprosy cases (two BT
      and one BB) along with their CD4 counts and HIV staging with anti-leprosy
      therapeutic response. Both BT cases responded well to conventional WHO MDT (PB)
      for 6 months, whereas the BB case relapsed 3 months after completion of MDT (MB)
      for one year. However, he became inactive again following a further one-year
      course of MDT (MB).

PMID- 15242275
TI  - Milestones in the genetical research on rhizobia.
AB  - The first isolation of the rhizobial bacteria from the legume roots was done in
      1888. Since then a large number of scientists have made efforts to understand the
      molecular basis of Rhizobium-legume symbiosis. The important developments of 115
      years of genetical research on rhizobia have been listed in this article.

PMID- 15242276
TI  - Regulation of expression of symbiotic genes in Rhizobium sp. NGR234.
AB  - Research in the field of Rhizobium-legume symbiosis faces a new challenge:
      integrate the wealth of information generated by genomic projects. The goal:
      apprehend the complexity of the molecular mechanisms involved in symbiotic
      associations. At the time of writing, the genomes of three micro-symbionts
      (Bradyrhizobium japonicum, Mesorhizobium loti and Sinorhizobium meliloti) have
      been sequenced, and two more (those of Rhizobium leguminosarum and Rhizobium
      etli) will be completed in the near future. Together, completed rhizobial genomes
      represent already 23,393,822 bp of DNA sequence and 21,797 predicted open reading
      frames (ORFs). To identify candidate-symbiotic genes in such a broad database,
      predict their function and dissect the regulatory networks that govern their
      expression are no simple tasks. One way to confront this problem is to combine
      different datasets, in particular genetic and transcriptional maps as well as
      predicted promoters from bioinformatics analyses. Here, we would like to
      illustrate this type of approach with the analysis of the symbiotic plasmid
      (pNGR234a) of the broad host-range Rhizobium sp. NGR234.

PMID- 15242277
TI  - Molecular aspects of soybean cultivar-specific nodulation by Sinorhizobium fredii
      USDA257.
AB  - Sinorhizobium fredii USDA257 forms nitrogen-fixing nodules in association with
      the primitive soybean cultivar 'Peking' but fails to initiate nodules on many
      advanced soybean cultivars, including 'McCall'. This distinction is controlled by
      a set of nodulation genes termed nolXWBTUV. Inactivation of any of these genes
      enables USDA257 to nodulate McCall and many other improved soybean cultivars.
      Mutation in the nolXWBTUV locus also alters the Nod factor structure resulting in
      the production of a novel molecule with glucose incorporated into the chitin
      backbone. Some of the genes located in the nolXWBTUV locus reveal sequence
      homologies to known components of the type III secretion system (TTSS) of plant
      and animal pathogenic bacteria. Recent studies have demonstrated the presence of
      a complete TTSS in USDA257 and few other symbiotic bacteria. The TTSS cluster of
      USDA257 contains 27 open reading frames out of which 10 code for the structural
      components of the TTSS. USDA257, when grown in presence of flavonoids, secrete
      several proteins called Nops (Nodulation Outer Proteins) into the extracellular
      environment. Genes located in the TTSS of USDA257 encode some of the
      extracellular proteins, such as NopX, NopB, and NopL. These type III secreted
      proteins appear to play an important role in regulating nodulation in a host
      dependent manner. Failure to elaborate the Nops results in a drastic phenotypic
      effect on soybean nodulation, indicating that these proteins may play a pivotal
      role in soybean cultivar specificity. The secretion of Nops appears to be
      facilitated by novel filamentous appendages (pili) that are produced by USDA257
      upon induction by flavonoids. Biochemical studies have demonstrated the close
      association of several Nops with the purified pili. However, it remains to be
      seen if the filamentous appendages can function as conduits for delivery of Nops
      into the host cell. This review examines the current state of our knowledge on
      the molecular aspects of soybean cultivar-specific nodulation by USDA257.

PMID- 15242278
TI  - Cysteine proteases in nodulation and nitrogen fixation.
AB  - The cysteine proteinases or cysteine endopeptidases (EC 3.4.22) are known to
      occur widely in plant cells. They are involved in almost all aspects of plant
      growth and development including germination, circadian rhythms, senescence and
      programmed cell death. They are also involved in mediating plant cell responses
      to environmental stress (such as water stress, salinity, low temperature,
      wounding, ethylene, and oxidative conditions) and plant-microbe interactions
      (including nodulation). In the development and function of legume root nodules,
      cysteine proteases could be involved in several important processes:-(i) a
      defence response to root invasion by microorganisms; (ii) protein turnover
      required during the formation of new tissue; (iii) cellular homeostasis and
      metabolism; (iv) adaptation of host cells to physiological stresses; (v) control
      of nodule senescence. Because of their central importance to plant physiology,
      cysteine proteases could serve as important targets for the study of nodule
      development and functioning at the molecular level. Because of their widespread
      occurrence in nodulating plants they could also serve as candidate genes for
      targeted plant breeding programmes.

PMID- 15242279
TI  - Proteomics: a novel approach to explore signal exchanges in Rhizobium-legume
      symbiosis.
AB  - Recent developments and future strategies on the proteomics approach to explore
      the signal exchanges in Rhizobium-legume symbiosis have been discussed. It is
      expected that this approach will provide new possibilities for investigating the
      complex interactions of rhizobia and legumes.

PMID- 15242280
TI  - Effects of drought stress on legume symbiotic nitrogen fixation: physiological
      mechanisms.
AB  - Drought stress is one of the major factors affecting nitrogen fixation by legume
      rhizobium symbiosis. Several mechanisms have been previously reported to be
      involved in the physiological response of symbiotic nitrogen fixation to drought
      stress, i.e. carbon shortage and nodule carbon metabolism, oxygen limitation, and
      feedback regulation by the accumulation of N fixation products. The carbon
      shortage hypothesis was previously investigated by studying the combined effects
      of CO2 enrichment and water deficits on nodulation and N2 fixation in soybean.
      Under drought, in a genotype with drought tolerant N2 fixation, approximately
      four times the amount of 14C was allocated to nodules compared to a drought
      sensitive genotype. It was found that an important effect of CO2 enrichment of
      soybean under drought was an enhancement of photo assimilation, an increased
      partitioning of carbon to nodules, whose main effect was to sustain nodule
      growth, which helped sustain N2 rates under soil water deficits. The interaction
      of nodule permeability to O2 and drought stress with N2 fixation was examined in
      soybean nodules and led to the overall conclusion that O2 limitation seems to be
      involved only in the initial stages of water deficit stresses in decreasing
      nodule activity. The involvement of ureides in the drought response of N2
      fixation was initially suspected by an increased ureide concentration in shoots
      and nodules under drought leading to a negative feedback response between ureides
      and nodule activity. Direct evidence for inhibition of nitrogenase activity by
      its products, ureides and amides, supported this hypothesis. The overall
      conclusion was that all three physiological mechanisms are important in
      understanding the regulation of N2 fixation and its response of to soil drying.

PMID- 15242281
TI  - Effects of biotic and abiotic constraints on the symbiosis between rhizobia and
      the tropical leguminous trees Acacia and Prosopis.
AB  - N2-fixing, drought tolerant and multipurpose Acacia and Prosopis species are
      appropriate trees for reforestation of degraded areas in arid and semiarid
      regions of the tropics and subtropics. Acacia and Prosopis trees form N2-fixing
      nodules with a wide range of rhizobia, for example African acacias mainly with
      Sinorhizobium sp. and Mesorhizobium sp., and Australian acacias with
      Bradyrhizobium sp. Although dry and hot seasons restrict formation of N2-fixing
      nodules on Acacia and Prosopis spp., fully grown trees and their symbiotic
      partners are well adapted to survive in harsh growth conditions. This review on
      one hand deals with major constraints of arid and semiarid soils, i.e. drought,
      salinity and high soil temperature, which affect growth of trees and rhizobia,
      and on the other hand with adaptation mechanisms by which both organisms survive
      through unfavourable periods. In addition, defects in infection and nodulation
      processes due to various abiotic and biotic constraints are reviewed. This
      knowledge is important when Acacia and Prosopis seedlings are used for
      forestation of degraded areas in arid and semiarid tropics.

PMID- 15242282
TI  - Rhizobia as a biological control agent against soil borne plant pathogenic fungi.
AB  - Rhizobia promote the growth of plants either directly through N2 fixation, supply
      of nutrients, synthesis of phytohormones and solubilization of minerals, or
      indirectly as a biocontrol agent by inhibiting the growth of pathogens. The
      biocontrol effect of rhizobia is due to the secretion of secondary metabolites
      such as antibiotics and HCN. Siderophore production in iron stress conditions
      provides rhizobia an added advantage, resulting in exclusion of pathogens due to
      iron starvation.

PMID- 15242283
TI  - Symbiosis between Frankia and actinorhizal plants: root nodules of non-legumes.
AB  - In actinorhizal symbioses, filamentous nitrogen-fixing soil bacteria of the genus
      Frankia induce the formation of nodules on the roots of a diverse group of
      dicotyledonous plants representing trees or woody shrubs, with one exception,
      Datisca glomerata. In the nodules, Frankia fixes nitrogen and exports the
      products to the plant cytoplasm, while being supplied with carbon sources by the
      host. Possibly due to the diversity of the host plants, actinorhizal nodules show
      considerable variability with regard to structure, oxygen protection mechanisms
      and physiology. Actinorhizal and legume-rhizobia symbioses are evolutionary
      related and share several features.

PMID- 15242284
TI  - Recent advances in Rhizobium-legume symbiosis.
AB  - The research findings in the field of Rhizobium-legume symbiosis reported
      worldwide during the years 2002 and 2003 (up to September) have been summarized.
      The information is presented under the various topics, viz., isolation and
      characterization of rhizobial strains, physiological aspects of nitrogen
      fixation, rhizosphere interactions and root surface signals, genomics and
      proteomics, plant genes involved in nodule formation, bioremediation and
      biocontrol, and review articles and conference reports. The postal and e-mail
      addresses of the concerned scientists have also been included.

PMID- 15242285
TI  - Isolation and symbiotic characterization of transposon Tn5-induced arginine
      auxotrophs of Sinorhizobium meliloti.
AB  - Seventeen arginine auxotrophic mutants of Sinorhizobium meliloti Rmd201 were
      isolated by random transposon Tn5 mutagenesis using Tn5 delivery vector pGS9.
      Based on intermediate feeding studies, these mutants were designated as
      argA/argB/argC/argD/argE (ornithine auxotrophs), argF/argI, argG and argH
      mutants. The ornithine auxotrophs induced ineffective nodules whereas all other
      arginine auxotrophs induced fully effective nodules on alfalfa plants. In
      comparison to the parental strain induced nodule, only a few nodule cells
      infected with rhizobia were seen in the nitrogen fixation zone of the nodule
      induced by the ornithine auxotroph. TEM studies showed that the bacteroids in the
      nitrogen fixation zone of ornithine auxotroph induced nodule were mostly
      spherical or oval unlike the elongated bacteroids in the nitrogen fixation zone
      of the parental strain induced nodule. These results indicate that ornithine or
      an intermediate of ornithine biosynthesis, or a chemical factor derived from one
      of these compounds is required for the normal development of nitrogen fixation
      zone and transformation of rhizobial bacteria into bacteroids during symbiosis of
      S. meliloti with alfalfa plants.

PMID- 15242286
TI  - 11th International Congress on Molecular Plant-Microbe Interactions held at St.
      Petersburg--a report.
AB  - The report is a short summary of the most interesting presentations at the 11th
      International Congress on Molecular Plant-Microbe Interactions held during July
      18-27, 2003 at St. Petersburg, Russia. The key elements from several sessions on
      the legume-Rhizobium interactions have been discussed.

PMID- 15242287
TI  - Microbes in heavy metal remediation.
AB  - Heavy metal contamination due to natural and anthropogenic sources is a global
      environmental concern. Release of heavy metal without proper treatment poses a
      significant threat to public health because of its persistence, biomagnification
      and accumulation in food chain. Non-biodegradability and sludge production are
      the two major constraints of metal treatment. Microbial metal bioremediation is
      an efficient strategy due to its low cost, high efficiency and ecofriendly
      nature. Recent advances have been made in understanding metal--microbe
      interaction and their application for metal accumulation/detoxification. This
      article summarizes the potentials of microbes in metal remediation.

PMID- 15242288
TI  - Microbial biomass: an economical alternative for removal of heavy metals from
      waste water.
AB  - Today indiscriminate and uncontrolled discharge of metal contaminated industrial
      effluents into the environment has become an issue of major concern. Heavy
      metals, being non-biodegradable and persistent, beyond a permissible
      concentration form unspecific compounds inside the cells thereby causing cellular
      toxicity. The only alternative to remove them from the wastewater is by
      immobilizing them. The conventional methods adopted earlier for this purpose
      included chemical precipitation, oxidation, reduction, filtration,
      electrochemical treatment, evaporation, adsorption and ion-exchange resins. These
      methods require high energy inputs especially when it refers to dilute solutions.
      Here microbial biomass offers an economical option for removing heavy metals by
      the phenomenon of biosorption. Non-living or dead biomass sequester metal(s) on
      their cell surface due to certain reactive groups available like carboxyl, amine,
      imidazole, phosphate, sulphydryl, sulfate and hydroxyl. The process can be made
      economical by procuring spent biomass from industry or naturally available bulk
      biomass. A batch or a continuous process of removal of heavy metals directly from
      effluents can be developed in a fixed bed reactor using the immobilized biomass.
      Further biosorption potential of the biomass can be improved by various physical
      and chemical treatments. The availability of variety of microbial biomass and
      their metal binding potential makes it a economical and sustainable option for
      developing effluent treatment process for removal and recovery of heavy metals.

PMID- 15242289
TI  - Biorecovery of gold.
AB  - Recovery of ionic and metallic gold (Au) from a wide variety of solutions by
      selected species of bacteria, yeasts, fungi, algae, and higher plants is
      documented. Gold accumulations were up to 7.0 g/kg dry weight (DW) in various
      species of bacteria, 25.0 g/kg DW in freshwater algae, 84.0 g/kg DW in peat, and
      100.0 g/kg DW in dried fungus mixed with keratinous material. Mechanisms of
      accumulation include oxidation, dissolution, reduction, leaching, and sorption.
      Uptake patterns are significantly modified by the physicochemical milieu. Crab
      exoskeletons accumulate up to 4.9 g Au/kg DW; however, gold accumulations in
      various tissues of living teleosts, decapod crustaceans, and bivalve molluscs are
      negligible.

PMID- 15242290
TI  - Bioremediation of chromium contaminated environments.
AB  - Bioremediation is the most promising and cost effective technology widely used
      nowadays to clean up both soils and wastewaters containing organic or inorganic
      contaminants. Discharge of chromium containing wastes has led to destruction of
      many agricultural lands and water bodies. Utilisation of chromium(Cr) reducing
      microbes and their products has enhanced the efficiency of the process of
      detoxification of Cr(VI) to Cr(III). This review focuses mainly on the current
      technologies prevalent for remediation like natural attenuation, anaerobic packed
      bed bioreactors (using live cells, Cr(VI) reductases or their byproducts) and use
      of engineered microorganisms. Treatment of wastewaters by biosorption or using
      biofilms and immobilized microbial cells are also discussed.

PMID- 15242291
TI  - Biosorption and elution of chromium from immobilized Bacillus coagulans biomass.
AB  - Bacillus coagulans, a tannery wastewater isolate, previously shown to bind
      dissolved Cr(VI), retained its ability to biosorb Cr(VI) in different matrices.
      Polymeric materials like agar, agarose, calcium alginate and polyacrylamide were
      screened. Agarose emerged as the suitable candidate for biomass immobilization
      mainly due to its higher stability and integrity in acidic pH. Aptness of agarose
      as the matrix for B. coagulans biomass was revealed during Cr(VI) biosorption
      from natural wastewater.

PMID- 15242292
TI  - Biodegradation of nitro-explosives.
AB  - Environmental contamination by nitro compounds is associated principally with the
      explosives industry. However, global production and use of explosives is
      unavoidable. The presently widely used nitro-explosives are TNT
      (Trinitrotoluene), RDX (Royal Demolition Explosive) and HMX (High Melting
      Explosive). Nevertheless, the problems of these nitro-explosives are almost
      parallel due to their similarities of production processes, abundance of nitro
      explosives and resembling chemical structures. The nitro-explosives per se as
      well as their environmental transformation products are toxic, showing symptoms
      as methaemoglobinaemia, kidney trouble, jaundice etc. Hence their
      removal/degradation from soil/water is essential. Aerobic and anaerobic
      degradation of TNT and RDX have been reported, while for HMX anaerobic or anoxic
      degradation have been described in many studies. A multisystem involvement using
      plants in remediation is gaining importance. Thus the information about
      degradation of nitro-explosives is available in jigsaw pieces which needs to be
      arranged and lacunae filled to get concrete degradative schemes so that
      environmental pollution from nitro-explosives can be dealt with more successfully
      at a macroscale. An overview of the reports on nitro-explosives degradation,
      future outlook and studies done by us are presented in this review.

PMID- 15242293
TI  - Separation and recovery of radioactive and non-radioactive toxic trace elements
      from aqueous industrial effluents.
AB  - An update is presented on liquid membrane-based processes as viable and relevant
      alternatives to conventional approaches such as precipitation, solvent
      extraction, ion exchange processes and electrochemical techniques for the removal
      and recovery of some toxic and/or valuable trace metal ions including some
      actinides and fission products e.g. U, Am, Y etc and As, Cd, Co, Cr, Cu, Hg, Ni,
      Pb, Zn etc from radioactive as well as non-radioactive aqueous waste solutions
      respectively. In particular, results of experiments aimed at developing supported
      liquid membrane(SLM)-based process using commercially available porous membranes
      and indigenously prepared track--etch membranes (TEMs) have been critically
      examined in laboratory studies to generate basic data needed to evaluate their
      utility for continuous operation without regeneration. These include effect of
      pore size, porosity, optimum pore size and their reusability. It is clearly
      demonstrated that indigenously prepared 10 microm thick TEMs with a porosity in
      the range of 2-5% give comparable transport rates for metal ions-matching with
      that of commercial membranes of much higher thickness (160 microm) and higher
      porosity of 60-85%. The smaller thickness of TEMs more than compensates for their
      lower porosity. It is shown that because of their well defined pore
      characteristics TEMs could serve as model supports in SLM studies. By comparing
      the values of permeability coefficient (P) for TEM and polytetraflouroethylene
      (PTFE) supports for the transport of Pb2+ chosen as a typical divalent metal ion,
      and using di-2 ethyl hexyl phosphoric acid (D2EHPA) as the carrier, it is
      unambiguously proved that diffusion of the metal complex across the membrane is
      the rate controlling step in metal ion transport in SLM-based processes. An
      overview of the experimental findings along with future outlook and suggestions
      for further work are presented in this paper.

PMID- 15242294
TI  - Microbiologically influenced corrosion in petroleum product pipelines--a review.
AB  - Microbiologically influenced corrosion is responsible for most of the internal
      corrosion problems in oil transportation pipelines and storage tanks. One
      problematic area in treating gas lines is the occurrence of the stratification of
      water in the line. Under these conditions, corrosion inhibitors do not come into
      contact properly and oil and inhibitors undergo degradation. The role of bacteria
      on oil degradation, the consequences of oil degradation in fuel systems and its
      influence on corrosion have been explained in detail. Besides, factors
      influencing on degradation of oil and corrosion inhibitors have also been
      discussed. Mechanism of microbiologically influenced corrosion in oil pipeline
      has been explained. Many of the misapplication of biocides/inhibitors occur
      mainly because the characteristics of biocides/inhibitors are not considered
      before use in pipeline industry. List of biocides and monitoring programme have
      been collected from literature and presented.

PMID- 15242295
TI  - Control of metallic corrosion through microbiological route.
AB  - Involvement of biofilm or microorganisms in corrosion processes is widely
      acknowledged. Although majority of the studies on microbiologically induced
      corrosion (MIC) have concentrated on aerobic/anaerobic bacteria. There are
      numerous aerobic bacteria, which could hinder the corrosion process. The
      microbiologically produced exopolymers provide the structural frame work for the
      biofilm. These polymers combine with dissolved metal ions and form organometallic
      complexes. Generally heterotrophic bacteria contribute to three major processes:
      (i) synthesis of polymers (ii) accumulation of reserve materials like poly-beta
      hydroxy butrate (iii) production of high molecular weight extracellular
      polysaccharides. Poly-beta-hydroxy butyrate is a polymer of D(-)beta-hydroxy
      butrate and has a molecular weight between 60,000 and 2,50,000. Some
      extracellular polymers also have higher molecular weights. It seems that higher
      molecular weight polymer acts as biocoating. In the present review, role of
      biochemistry on corrosion inhibition and possibilities of corrosion inhibition by
      various microbes are discussed. The role of bacteria on current demand during
      cathodic protection is also debated. In addition, some of the significant
      contributions made by CECRI in this promising area are highlighted.

PMID- 15242296
TI  - Bioremediation: an important alternative for soil and industrial wastes clean-up.
AB  - Industrial and environmental biotechnology are going to new paths, resulting in
      processes with "clean technologies", with the maximum production and the less
      residues. Technologies of remediation and bioremediation are continuously being
      improved using genetically modified microorganisms or those naturally occurring,
      to clean residues and contaminated areas from toxic organics. Bioremediation of
      soils, water and marine environments has many advantages but at the same time it
      is a challenge for the researchers and engineers. Consequently, it is extremely
      important to carry out feasibility study based on pilot-testing before starting a
      remediation project in order to determine the best conditions for the process.
      The article presents a brief review of bioremediation including the description
      of the different methods applied to soil and industrial wastes, and, finally,
      some experiences of solid-state fermentation in relation to bioremediation.

PMID- 15242297
TI  - Anaerobic biodegradation of aromatic compounds.
AB  - Many aromatic compounds and their monomers are existing in nature. Besides they
      are introduced into the environment by human activity. The conversion of these
      aromatic compounds is mainly an aerobic process because of the involvement of
      molecular oxygen in ring fission and as an electron acceptor. Recent literatures
      indicated that ring fission of monomers and obligomers mainly occurs in anaerobic
      environments through anaerobic respiration with nitrate, sulphate, carbon dioxide
      or carbonate as electron acceptors. These anaerobic processes will help to work
      out the better situation for bioremediation of contaminated environments. While
      there are plenty of efforts to reduce the release of these chemicals to the
      environment, already contaminated sites need to be remediated not only to restore
      the sites but to prevent the leachates spreading to nearby environment. Basically
      microorganisms are better candidates for breakdown of these compounds because of
      their wider catalytic mechanisms and the ability to act even in the absence of
      oxygen. These microbes can be grouped based on their energy mechanisms. Normally,
      the aerobic counterparts employ the enzymes like mono-and-dioxygenases. The end
      product is basically catechol, which further may be metabolised to CO2 by means
      of quinones reductases cycles. In the absense of reductases compounds, the
      reduced catechols tend to become oxidised to form many quinone compounds. The
      quinone products are more recalcitrant and lead to other aesthetic problems like
      colour in water, unpleasant odour, etc. On the contrary, in the reducing
      environment this process is prevented and in a cascade of pathways, the cleaved
      products are converted to acetyl co-A to be integrated into other central
      metabolite paths. The central metabolite of anaerobic degradation is invariably
      co-A thio-esters of benzoic acid or hydroxy benzoic acid. The benzene ring
      undergoes various substitution and addition reactions to form chloro-, nitro-,
      methyl- compounds. For complete degradation the side chains must be removed first
      and then the benzene ring is activated by carboxylation or hydroxylation or co-A
      thioester formation. In the next step the activated ring is converted to a form
      that can be collected in the central pool of metabolism. The third step is the
      channeling reaction in which the products of the catalysis are directed into
      central metabolite pool. The enzymes involved in these mechanisms are mostly
      benzyl co-A ligase, benzyl alcohol dehydrogenase. Other enzymes involved in this
      path are yet to be purified though many of the reactions products that have been
      theoretically postulated have been identified. This is mainly due to the
      instability of intermediate compounds as well as the association of the enzyme
      substrate is femoral and experimental conditions need to be sophisticated further
      for isolation of these enzymes. The first structural genes of benzoate and
      hydroxy benzoate ligases were isolated from Rhodopseudomonas palustris. This gene
      cluster of 30 kb size found in Rhodopseudomonas palustris coded for the Bad A
      protein. Similarly, some of the bph A,B,C and D cluster of genes coding for the
      degradation of pentachlorobenzenes were located in Pseudomonas
      pseudoalgaligenesKF 707.

PMID- 15242298
TI  - Bioremediation concepts for treatment of dye containing wastewater: a review.
AB  - Synthetic dyes are extensively used in wide range of industries amongst which
      textile processing industries are the major consumers. Large amounts of dyes are
      lost in wastewaters of these industries during dyeing and subsequent washing
      steps of textiles. These dyes are resistant to de gradation by conventional
      wastewater treatment plants and are released into environment untreated thus
      causing pollution of surface and ground waters in the areas of the world
      harboring such industries. Presence of color in wastewaters has become major
      environmental concern and stringent discharge standards are being enforced on
      release of colored wastewaters in environment. The seriousness of the problem is
      apparent from the magnitude of the research done in this field in last decade.
      Increasing number of microorganisms are being described for their ability to
      decolorize and degrade artificial dyes and novel bioremediation approaches for
      treatment dye bearing wastewaters are being worked out. In this review we have
      investigated potential microbial processes for developing feasible remediation
      technology to combat environmental pollution due to dye bearing wastewaters.

PMID- 15242300
TI  - Polymyalgia rheumatica: not well understood, but important to consider.

PMID- 15242299
TI  - Synthetic dye decolourization by white rot fungi.
AB  - Synthetic dyes are integral part of many industrial products. The effluents
      generated from textile dyeing units create major environmental problems and
      issues both in public and textile units. Industrial wastewater treatment is one
      of the major problems in the present scenario. Though, the physical and chemical
      methods offer some solutions to the problems, it is not affordable by the unit
      operators. Biological degradation is recognized as the most effective method for
      degrading the dye present in the waste. Research over a period of two decades had
      provided insight into the various aspects of biological degradation of dyes. It
      is observed that the white rot fungi have a non-specific enzyme system, which
      oxidizes the recalcitrant dyes. Detailed and extensive studies have been made and
      process developed for treatment of dye containing wastewaters by white rot fungi
      and their enzyme systems. An attempt is made to summarize the detailed research
      contributions on these lines.

PMID- 15242301
TI  - My patient has elevated prolactin and infertility, but normal periods and a
      negative pituitary study. What should I do?

PMID- 15242302
TI  - The challenge of valvular heart disease: when is it time to operate?
AB  - In patients with valve disease, operating too soon exposes them to unnecessary
      surgical risk, but waiting too long may lead to cardiac damage and poor outcome.
      When to refer a patient for surgery depends on which valve is involved, the type
      of defect (stenosis or regurgitation), the degree of the defect, and the degree
      of symptoms or functional impairment.

PMID- 15242303
TI  - Cardiac sarcoidosis: a cause of infiltrative cardiomyopathy.

PMID- 15242304
TI  - Polymyalgia rheumatica: clinical presentation is key to diagnosis and treatment.
AB  - Polymyalgia rheumatica should be considered in the differential diagnosis in
      patients over 50 years old who present with bilateral achiness and stiffness in
      the shoulders or hips or both. It usually responds quickly to once-daily, low
      dose prednisone, but some patients require treatment for several years.
      Polymyalgia rheumatica frequently overlaps with giant cell arteritis, and
      patients must be followed closely for development of complications from this
      condition, especially aortitis.

PMID- 15242305
TI  - Fecal-based DNA assays: a new, noninvasive approach to colorectal cancer
      screening.
AB  - Stool-based DNA testing is a new, noninvasive method of colorectal cancer
      screening. Because it is easier to use and more sensitive than fecal occult blood
      testing, physicians may be more likely to recommend it, and patients may be more
      apt to comply. Although it is expensive, initial assessments show it to be cost
      effective.

PMID- 15242306
TI  - An appropriate diagnostic workup for suspected vascular birthmarks.
AB  - Birthmarks are common and commonly ignored by patients and primary care doctors.
      Yet they sometimes represent significant vascular anomalies that require
      diagnosis and treatment. We summarize when and how to work up a variety of
      vascular anomalies.

PMID- 15242307
TI  - Gynecomastia: its features, and when and how to treat it.
AB  - Gynecomastia is common, being present in 30% to 50% of healthy men. A general
      medical history and careful physical examination with particular attention to
      features suggestive of breast cancer often suffice for evaluation in patients
      without symptoms or those with incidentally discovered breast enlargement. Men
      with recent-onset gynecomastia or mastodynia need a more detailed evaluation,
      including selected laboratory tests to search for an underlying cause. Treatment
      depends on the cause and may include observation, withdrawal of an offending
      drug, therapy of an underlying disease, giving androgen or antiestrogen drugs, or
      plastic surgery.

PMID- 15242308
TI  - [Is research saved?].

PMID- 15242309
TI  - [Membrane receptors borrow an indirect path against cancer].

PMID- 15242310
TI  - [The Aurora kinase inhibitor VX680, leader of a new family of antitumoral
      agents].

PMID- 15242311
TI  - [Ovca1 gene, deleted in ovarian cancer is a special tumor suppressor].

PMID- 15242312
TI  - [Identification and management of HNPCC syndrome (hereditary non polyposis colon
      cancer), hereditary predisposition to colorectal and endometrial
      adenocarcinomas].
AB  - BACKGROUND: The HNPCC syndrome (hereditary non polyposis colon cancer) is an
      inherited condition defined by clinical and genealogical information, known as
      Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline
      mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI
      phenotype). Patients affected by the disease are at high risk for colorectal and
      endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach
      and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal
      cancers. Identification and management of this disease are part of a
      multidisciplinary procedure. METHODS: 12 experts have been mandated by the French
      Health Ministry to analyze and synthesize their consensus position, and the
      resulting document has been reviewed by an additional group of 4 independent
      experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in
      recognizing patients carrying a MMR germline mutation led to an enlargement of
      these criteria for the recruitment of possible HNPCC patients, and to a 2-steps
      strategy, asking first for a tumor characterization according to MSI phenotype,
      especially in case of early-onset sporadic cases. The identification of germline
      MMR mutations has no major consequence on the cancer treatments, but influences
      markedly the long-term follow-up and the management of at-risk relatives. Gene
      carriers will enter a follow-up program regarding their colorectal and
      endometrial cancer risks, but other organs being at low lifetime risk, no
      specific surveillance will be proposed.

PMID- 15242313
TI  - [From cytogenetics to cytogenomics of adipose tissue tumors: 2. Malignant adipose
      tissue tumors].
AB  - Malignant adipose tissue tumors, also called liposarcomas, are the most common
      sarcoma of adult life. They may be hard to distinguish from benign adipose tissue
      tumors as well as from other types of sarcomas. Well-differentiated liposarcomas
      and myxoid liposarcomas are the two histological subtypes that have been best
      characterized at the genetic level. The defining genetic features of well
      differentiated liposarcoma cells are supernumerary circular ("ring") and giant
      linear rod chromosomes. These rings and giant chromosomes contain amplification
      of the 12q14-15 region, including the MDM2 gene, associated with coamplification
      of various other chromosomal regions. In addition, they most often lack alpha
      satellite centromeric sequences. The detection of MDM2 amplification is a
      valuable tool for the differential diagnosis between well-differentiated
      liposarcomas and lipomas. Dedifferentiated liposarcomas usually present with
      patterns of MDM2 amplification similar to those observed in well-differentiated
      liposarcomas. In addition, recent CGH-array studies suggest that co-amplification
      of MDM2 with the 6q23-25 region might be a specific feature. Myxoid and round
      cell liposarcomas are characterized by a translocation t(12;16)(q13;p11) that
      fuses the DDIT3 and FUS genes. A rare variant translocation t(12;22) that fuses
      DDIT3 with EWS has also been described. The genetics of pleomorphic liposarcoma
      is still obscure. Pleomorphic liposarcomas show complex karyotypes with many
      numerical and structural chromosomal aberrations. To date, no specific molecular
      abnormality has been identified.

PMID- 15242314
TI  - [PTPL1, a proapoptotic protein tyrosine phosphatase in breast cancers].
AB  - The protein tyrosine phosphatase L1 (PTPL1), also known as FAP1, has two major
      types of remarkable structural domains, in addition to its catalytic unit: a FERM
      domain which is responsible for its localization at the apical pole of the cell
      plasma membrane and 5 PDZ domains suggestive of numerous possibilities of protein
      partners and consequently of a role as a cargo protein or an integrator between
      different signalling pathways. In fact, though it was initially suggested, in
      1995, that this enzyme acts as an inhibitor of Fas death receptor several recent
      studies indicate that PTPL1 plays many other roles. It dephosphorylates Ephrin B
      (ligand of Eph, a receptor triggering angiogenesis and axonal guidance), it
      interacts with numerous proteins associated to cytoskeleton plasticity and it is
      implicated in cytokinesis. We have demonstrated that its expression is regulated
      by antiestrogens in mammary cancer and shown, with stable antisense
      transfectants, that PTPL1 plays a key role in the mediation of the inhibitory
      effects of these antagonists on growth factor signalling by impeding the IRS
      I/PI3-K/Akt survival pathway. Altogether PTPL1 has to be regarded as a unique
      marker of mammary tumor response to antiestrogens and a potential therapeutic
      target to activate apoptotic stimuli in tumor cells.

PMID- 15242315
TI  - [Brain metastases: a neurosurgical point of view].
AB  - The question of accessibility to the recent development of diagnostic and
      therapeutic tools for brain metastasis patients remains a problem. Advances in
      neurosurgery, new fields in chemotherapy, radiosurgery and different types of
      radiation therapy are accompanied by the need of dedicated staff time and
      materials. The limits of what we can offer to our patients regarding access to
      treatment and costs have to be clarified through a national consensus. Multimodal
      strategies must take in account the individual patient as well as accessibility
      to the different treatment tools. The most important problem remain the ongoing
      need for radiosurgery and various subtype of new radiotherapy methods.

PMID- 15242316
TI  - [Treatment of hot flashes in women with a previous diagnosis of breast cancer].
AB  - Due to the huge prescription of adjuvant chemotherapy and hormonotherapy, the
      number of breast cancer survivors with hot flashes is to raise. Hormone
      replacement therapy is typically withheld from women with previous breast cancer.
      Treatment should begin with a careful patient history, with specific attention to
      the frequency and severity of hot flashes and their effect on the individual's
      function. For mild symptoms that do not interfere with sleep or daily activity,
      behavioural changes or treatments like soy phyto-oetrogens or vitamin E could be
      a reasonable initial approach. For more severe symptoms, several alternative
      substances have therefore been investigated. The use of clonidine and gabapentine
      should be discouraged because of their modest efficacy and adverse effects. Newer
      antidepressants (selective serotonin reuptake inhibitors) that are the best
      studied drugs to date, appear promising as therapy for women with hot flashes.
      The decrease in hot flashes achieved with progestational agents is similar to
      that seen with oestrogen therapy but there is debate about the safety of long
      term use of progestational agents in patients with a history of breast cancer. If
      hot flashes are particularly troublesome and do not respond to alternative
      approaches, quality of life must be balanced against theoretical risk of tumour
      promotion before choosing to use hormone replacement therapy to control these
      symptoms.

PMID- 15242317
TI  - [An evidence-based patient information and patient education programme: the SOR
      SAVOIR PATIENT].
AB  - The development of good-quality patient information is a major challenge to
      improve quality of cancer care. The SOR SAVOIR PATIENT program aims to improve
      patients' understanding of cancer treatment and to facilitate their participation
      in clinical decisions. This programme develops evidence-based information for
      cancer patients based on clinical practice guidelines in oncology, the
      "Standards, Options and Recommendations" (SOR) which are used as primary
      information sources. "Translation" of SOR guidelines to laymen uses a
      multidisciplinary approach involving specialists in cancer care, psychologists,
      linguists and anthropologists. The development actively involves cancer patients
      using focus group methods, individual interviews and postal surveys. The SOR
      SAVOIR PATIENT program is conducted by the FNCLCC and the 20 French regional
      cancer centres, with active participation of specialists (public and private),
      learned societies and institutions, collaborating in multidisciplinary working
      groups. The leaflets Understanding scanner and Understanding Magnetic Resonance
      Imaging available in this edition of Bulletin du Cancer have been developed by a
      multidisciplinary group (radiologist, oncologist, methodologist, health care
      practioners, psychologist, linguist) and 30 patients, experienced patients and
      caregivers. These leaflets stem from a collection of patients documents on
      radiological examinations (Understanding mammography, Ultrasound, etc.) which
      have been developed to help patients and caregivers to better understand these
      examinations.

PMID- 15242318
TI  - [Understanding the MRI examination].

PMID- 15242319
TI  - [Understanding scans].

PMID- 15242320
TI  - [Larynx cancer in France: descriptive epidemiology and incidence estimation].
AB  - The epidemiology of cancers is known in France through mortality data provided by
      Inserm and morbidity data obtained by French tumor registries. The purpose of
      this study was to compare the incidence of laryngeal cancers in 9 French
      departments and to give an estimate of this incidence for the whole of France,
      based on this data. Incidence and mortality data were collected over the period
      1978-1997. The incidence and mortality rates were estimated for each year from
      1978 up to 2000. Observed incidence and mortality data in the population covered
      by cancer registries were modelled using age-cohort methods. An estimation of the
      incidence/mortality ratio was obtained from these models and applied to the
      mortality rates predicted from an age-cohort model for the entire French
      population. The estimated number of laryngeal cancers was 3,865 in males and 361
      in females. There were pronounced contrasts in laryngeal cancer incidence between
      cancer registries. The incidence rate of laryngeal cancers were especially high
      in the Somme and Calvados department compared to those observed in Haut-Rhin and
      Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is
      among the countries which have the highest rates of incidence and mortality for
      laryngeal cancer in Europe.

PMID- 15242321
TI  - [Contribution of serum Cyfra 21-1 in nasopharyngeal carcinoma in Tunisia].
AB  - Cyfra 21-1 is a recognised marker for epidermoid lung and head and neck
      carcinomas oriented to the cytokeratin 19 that is expressed particularly in
      malignant epithelial cells. The aims of this study were to evaluate the
      importance of the use of this marker in nasopharyngeal carcinoma (NPC). Our
      prospective study interested 41 patients (33M/8F) with a mean age of 44 years (13
      to 70) with 8 of them aged less than 30 years, presenting a nasopharyngeal
      carcinoma histologically confirmed from September 1999 to March 2000 and 45
      healthy controls without evidence neoplasm. Undifferentiated forms represent
      90.2% of cases and lesions are staged T2, T3 and T4 in 2.4%, 36.6% and 61% of
      cases, while N1, N2 and N3 represent 9.8%, 26.8% and 41.5% of cases. A blood
      sample was collected from each patient and control before any treatment, as well
      as controls to measure Cyfra 21-1 by immunoenzymatic assay, 2 groups of patients
      were selected after a period varying from 4 to 37 months with a median of 29
      months: 27 patients with favourable evolution (without evidence of disease after
      initial treatment), 12 patients with non favourable evolution (1 death, 2 cases
      of loco-regional relapse and 9 patients with metastatic disease). 2 patients were
      lost to follow-up. The results showed that the mean serum Cyfra 21-1 values were
      significantly higher in patients with NPC than those in controls (p = 0.001). A
      significant correlation was found between the serum Cyfra 21-1 level before
      treatment and the clinical outcome of patients (p = 0.0009). Patients having a
      favourable evolution have the lowest level. Seric level of Cyfra 21-1 at
      diagnosis of NPC may play a predictive role to evaluate the risk of metastatic
      disease and prognosis.

PMID- 15242322
TI  - [Identification of prognostic factors in post-transplantation lymphoproliferative
      disorders].
AB  - Post-transplantation lymphoproliferative disorders (PTLD) represent a severe
      complication of organ transplantation, so the determination of prognostic factors
      for the response and the survival is of major interest. Studies on PTLD are
      hindered by the small number of cases, explaining the conflicting published
      results. In order to identify, prognostic factors in this kind of disease, 61
      patients have been analyzed in a retrospective multicenter study. A new index is
      proposed to assess the survival probability, it is composed of two factors: the
      performance status (PS < or = 1 versus 2-3) and the number of involved sites (1
      versus > 1). This index seems to be more accurate in PTLD than the IPI, the
      reference in immunocompetent patients with non Hodgkin lymphomas. However, a
      similar analysis in a more homogeneous population remains necessary.

PMID- 15242323
TI  - [Sentinel lymph node biopsy in cervical and endometrial cancers: a feasibility
      study].
AB  - The sentinel lymph node (SLN) biopsy has been proposed for the cancers of the
      uterus in order to optimize the diagnosis of lymphatic metastases and
      micrometastases in early stage tumors. Patients with early invasive cervical (n =
      8) or endometrial (n = 15) cancers were enrolled. A lymphoscintigraphy was
      carried out before the intervention. Intraoperative SLN identification was
      performed with blue dye combined to a handheld gamma probe detection. Non
      sentinel pelvic nodes were separately cleared out. SLNs were examined with frozen
      sections, permanent sections with hematoxylin-eosin staining and further serial
      sections with immunohistochemistry if negative. Six cervical cancer patients and
      13 endometrial cancer patients had a positive lymphoscintigraphy, showing in 5
      patients extra-iliac SLN(s). The intraoperative detection was successful in 6
      cervical cancer patients and 14 endometrial cancer patients. The higher detection
      rate was obtained with the isotopic method. Most of the SLNs were ilio-obturator.
      Four endometrial cancer patients had a lymphatic spread, only involving the SLN
      in each case. No false negative SLN has been noted. SLN biopsy appears feasible
      in cervical and endometrial cancers. This procedure could improve the lymphatic
      evaluation of these cancers.

PMID- 15242324
TI  - When doctors are the victims. Targeted for attack and kidnappings, many are
      getting out of Iraq.

PMID- 15242325
TI  - Introduction: managing bipolar depression.

PMID- 15242326
TI  - Correlates of suicidal behavior and lithium treatment in bipolar disorder.
AB  - Individuals with bipolar and major depressive disorders have considerably higher
      suicide rates than the general population. However, estimating the risk of
      suicide is complicated, and there exists a general lack of consensus among
      researchers regarding whether suicide rates are higher in patients with unipolar,
      bipolar I, or bipolar II depressive disorders. Isolating the specific factors
      that contribute to the high risk of suicide in patients with affective disorders
      can be challenging as well; substance and alcohol abuse, family history of
      suicide, differences in allele distributions, comorbid anxiety, depression
      recurrence, seasonal effects, rapid cycling, and a history of hospitalizations
      for depression all appear to contribute to the likelihood that these patients
      will engage in suicidal behavior. Research does tend to agree that lithium is
      efficacious in decreasing suicidal behavior in patients with affective disorders.

PMID- 15242327
TI  - Evaluation and management of breakthrough depressive episodes.
AB  - Clinicians are faced with a diagnostic challenge when a bipolar patient reports
      breakthrough depressive symptomatology. Breakthrough depressive symptoms during
      treatment for a bipolar depressive episode may be a manifestation of recurrent
      bipolar depression or the emergence of a mixed episode. Treatment of recurrent
      bipolar depression and mixed episodes differs considerably, and antidepressant
      therapy during a mixed episode can worsen the episode and initiate or exacerbate
      rapid cycling. Therefore, accurate diagnosis and appropriate treatment are
      imperative to achieving a positive outcome. Research indicates that optimizing
      the current mood stabilizer therapy or adding another mood stabilizer may be the
      best treatment options for patients with a history of rapid cycling-in patients
      without a history of rapid cycling, adding an antidepressant to a mood stabilizer
      may be less risky and therefore a reasonable choice. Combination therapy with a
      mood stabilizer and an atypical antipsychotic may also be effective in managing
      bipolar depressive episodes.

PMID- 15242328
TI  - Strategies for preventing the recurrence of bipolar disorder.
AB  - In interpreting the maintenance literature for bipolar disorder, attention needs
      to be paid to important methodological issues. In this article, we initially
      examine the methodological topics that need to be considered, and we then examine
      the content of the evidence regarding maintenance treatments. Agents used in the
      long-term treatment of bipolar disorder possess varying degrees of supportive
      evidence. By consensus, the number of randomized studies and years of clinical
      experience with lithium mark it as the evidentially strongest long-term agent for
      bipolar disorder. Recent studies also demonstrate likely long-term benefit with
      lamotrigine, and possibly olanzapine. Although we possess fewer randomized data,
      some such evidence exists and, along with clinical experience, supports the
      likely long-term utility of valproate in the treatment of bipolar disorder as
      well. Some psychotherapies also may possess adjunctive maintenance efficacy.

PMID- 15242329
TI  - The importance of subsyndromal symptoms in bipolar disorder.
AB  - Bipolar disorder continues to be characterized by poor clinical and functional
      outcomes in many patients. Poor outcomes may be related to subsyndromal symptoms,
      defined as symptoms that fail to meet the full diagnostic criteria for a mood
      episode. Several recent studies indicate that subsyndromal symptoms in bipolar
      disorder are strongly associated with deficits in both social and occupational
      functioning. Furthermore, subsyndromal symptoms appear to increase the risk of
      relapse. Combined, these factors emphasize the importance of aggressive treatment
      strategies at the onset of subsyndromal symptoms. In addition, the use of
      subsyndromal symptoms to broaden the diagnostic criteria for bipolar disorder is
      receiving increased attention. This article reviews and discusses these important
      issues.

PMID- 15242330
TI  - Newer anticonvulsants in the treatment of bipolar disorder.
AB  - The anticonvulsants valproate and carbamazepine have efficacy in treating acute
      mania, but their efficacy in treating acute bipolar depression and preventing
      mood episodes remains uncertain. Despite this, and given their utility and
      widespread use, both are widely accepted as standard treatments for bipolar
      disorder. All the newer anticonvulsants that have become available during the
      last decade have been or are being assessed to determine their efficacy in the
      treatment of various phases of bipolar disorder. Among the newer anticonvulsants,
      some appear to have efficacy in treating core bipolar symptoms, while others have
      efficacy in treating psychiatric comorbidity such as substance abuse or an
      anxiety disorder. Lamotrigine is the most widely studied and is effective in
      treating and preventing bipolar depression, and it is the only anticonvulsant
      approved by the U.S. Food and Drug Administration as a maintenance treatment for
      bipolar disorder. Other newer anticonvulsants, levetiracetam, oxcarbazepine,
      phenytoin, and zonisamide offer promise, but further studies are required before
      they can be recommended for routine use to treat bipolar disorder. Gabapentin and
      topiramate do not appear to have efficacy in treating acute mania, but their
      utility in bipolar depression and prevention of mood episodes has not been
      studied in double-blind trials. Pregabalin has utility in treating generalized
      anxiety disorder, but it has not been studied in bipolar disorder. Given the
      success of lamotrigine in treating bipolar disorder, further double-blind
      controlled trials of the newer anticonvulsants in treating bipolar disorder are
      warranted. This article summarizes current evidence from trials of
      anticonvulsants in bipolar disorder and makes recommendations for their clinical
      use.

PMID- 15242331
TI  - Sp1 and Smad transcription factors co-operate to mediate TGF-beta-dependent
      activation of amyloid-beta precursor protein gene transcription.
AB  - Abnormal deposition of Abeta (amyloid-beta peptide) is one of the hallmarks of AD
      (Alzheimer's disease). This peptide results from the processing and cleavage of
      its precursor protein, APP (amyloid-beta precursor protein). We have demonstrated
      previously that TGF-beta (transforming growth factor-beta), which is
      overexpressed in AD patients, is capable of enhancing the synthesis of APP by
      astrocytes by a transcriptional mechanism leading to the accumulation of Abeta.
      In the present study, we aimed at further characterization of the molecular
      mechanisms sustaining this TGF-beta-dependent transcriptional activity. We report
      the following findings: first, TGF-beta is capable of inducing the
      transcriptional activity of a reporter gene construct corresponding to the
      +54/+74 region of the APP promoter, named APP(TRE) (APP TGF-beta-responsive
      element); secondly, although this effect is mediated by a transduction pathway
      involving Smad3 (signalling mother against decapentaplegic peptide 3) and Smad4,
      Smad2 or other Smads failed to induce the activity of APP(TRE). We also observed
      that the APP(TRE) sequence not only responds to the Smad3 transcription factor,
      but also the Sp1 (signal protein 1) transcription factor co-operates with Smads
      to potentiate the TGF-beta-dependent activation of APP. TGF-beta signalling
      induces the formation of nuclear complexes composed of Sp1, Smad3 and Smad4.
      Overall, the present study gives new insights for a better understanding of the
      fine molecular mechanisms occurring at the transcriptional level and regulating
      TGF-beta-dependent transcription. In the context of AD, our results provide
      additional evidence for a key role for TGF-beta in the regulation of Abeta
      production.

PMID- 15242332
TI  - Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation
      of polymerase I and transcript release factor (PTRF) at the surface of caveolae
      in human adipocytes.
AB  - Caveolae, the specialized invaginations of plasma membranes, formed sealed
      vesicles with outwards-orientated cytosolic surface after isolation from primary
      human adipocytes. This morphology allowed differential, vectorial identification
      of proteins at the opposite membrane surfaces by proteolysis and MS.
      Extracellular-exposed caveolae-specific proteins CD36 and copper-containing amine
      oxidase were concealed inside the vesicles and resisted trypsin treatment. The
      cytosol-orientated caveolins were efficiently digested by trypsin, producing
      peptides amenable to direct MS sequencing. Isolation of peripheral proteins
      associated with the cytosolic surface of caveolae revealed a set of proteins that
      contained nuclear localization signals, leucine-zipper domains and PEST (amino
      acid sequence enriched in proline, glutamic acid, serine and threonine) domains
      implicated in regulation by proteolysis. In particular, PTRF (polymerase I and
      transcript release factor) was found as a major caveolae-associated protein and
      its co-localization with caveolin was confirmed by immunofluorescence confocal
      microscopy. PTRF was present at the surface of caveolae in the intact form and in
      five different truncated forms. Peptides (44 and 45 amino acids long) comprising
      both the PEST domains were sequenced by nanospray-quadrupole-time-of-flight MS
      from the full-length PTRF, but were not found in the truncated forms of the
      protein. Two endogenous cleavage sites corresponding to calpain specificity were
      identified in PTRF; one of them was in a PEST domain. Both cleavage sites were
      flanked by mono- or diphosphorylated sequences. The phosphorylation sites were
      localized to Ser-36, Ser-40, Ser-365 and Ser-366 in PTRF. Caveolae of human
      adipocytes are proposed to function in targeting, relocation and proteolytic
      control of PTRF and other PEST-domain-containing signalling proteins.

PMID- 15242333
TI  - Protein arginine methylation during lytic adenovirus infection.
AB  - Arginine methylation of proteins affects major processes in the cell, including
      transcriptional regulation, mRNA metabolism, signal transduction and protein
      sorting. Arginine methylation of Ad (adenovirus) E1B 55-kDa-associated protein
      E1B-AP5 was recently described by us [Kzhyshkowska, Schutt, Liss, Kremmer,
      Stauber, Wolf and Dobner (2001) Biochem. J. 358, 305-314]. In this first example
      of protein arginine methylation analysis in Ad-infected cells, we investigated
      methylation of the E1B-AP5 and the viral L4-100 kDa protein. We demonstrate that
      E1B-AP5 methylation is enhanced during the course of infection in a cell-type
      specific manner. We also show that L4-100 kDa is efficiently methylated in Ad
      infected cells. L4-100 kDa formed complex with methyltransferase in vivo during
      productive infection, and can be methylated by HRMT1L2 (human protein arginine
      methyltransferase 1) in vitro. Comparative analysis of E1B-AP5 and L4-100 kDa
      protein methylation in Ad-infected HeLa, MCF-7 and H1299 cells revealed that the
      profile of protein arginine methylation correlates with the efficiency of Ad
      proteins production. Our results suggest that protein arginine methylation is an
      important host-cell function required for efficient Ad replication.

PMID- 15242334
TI  - The fractal structure of polycation-DNA complexes.
AB  - We used static light scattering to obtain new measurements on the internal
      structure of aggregated non-viral gene-delivery particles in colloidal
      suspension. The vector particles are prepared by charge neutralization of plasmid
      DNA either by poly-L-lysine or by a Lipofectin/integrin-targeting peptide. We use
      established theories of the stability of colloidal particles and fractal concepts
      to explain the aggregation processes and demonstrate the existence of a new
      property (fractal dimension) of the aggregated vector particles. Aggregation is
      shown to produce particles with fractal dimensions in the range between 1.8 and
      2.4; the former suggests a loose three-dimensional structure and the latter
      characterizes an aggregation process that leads to the formation of particles
      with tightly packed structures. We show that the fractal dimension of the vector
      particles is sensitive to changes in physicochemical conditions (ionic strength)
      of the buffer solution and propose that fractal dimension may provide a useful
      means of monitoring the physical state of non-viral delivery-vector particles
      during preparation and storage.

PMID- 15242335
TI  - Sex, drugs and gene expression: signalling by members of the nuclear receptor
      superfamily.
AB  - It is almost 20 years since the first steroid receptor cDNAs were cloned, a
      development that led to the concept of a superfamily of ligand-activated
      transcription factors: the nuclear receptors. Natural ligands for nuclear
      receptors are generally lipophilic in nature and include steroid hormones, bile
      acids, fatty acids, thyroid hormones, certain vitamins and prostaglandins.
      Nuclear receptors act principally to directly control patterns of gene expression
      and play vital roles during development and in the regulation of metabolic and
      reproductive functions in the adult organism. Since the original cloning
      experiments, considerable progress has been made in our understanding of the
      structure, mechanisms of action and biology of this important family of proteins.

PMID- 15242336
TI  - The evolution of the nuclear receptor superfamily.
AB  - Nuclear receptors form a superfamily of ligand-activated transcription factors
      implicated in various physiological functions from development to homoeostasis.
      Nuclear receptors share a common evolutionary history revealed by their conserved
      structure and by their high degree of sequence conservation. Here we review the
      latest advances on the evolution of nuclear receptors by addressing the following
      questions. What is known about the appearance and diversification of nuclear
      hormone receptors? How did their different functional characteristics evolve?
      What can we infer from the analysis of complete genomes? In summary, the study of
      the evolution of nuclear receptors will be very important not only for
      understanding their functions in vivo but also for obtaining insights into the
      evolution of animal genomes as a whole.

PMID- 15242337
TI  - Overview of the structural basis for transcription regulation by nuclear hormone
      receptors.
AB  - The mechanism of action of the nuclear hormone receptors (NHRs) as gene-
      regulatory molecules has become a major focus of current biological interest.
      NHRs belong to the superfamily of ligand-activated transcription factors, which
      are involved in the regulation of homoeostasis, reproduction, development and
      differentiation. To fully understand their functions, it is important to know the
      functional three-dimensional structure of these proteins. Molecular cloning and
      structure-function analyses have revealed that NHRs commonly have three
      functional regions: the N-terminal, DNA-binding and ligand-binding domains.
      Structures of some of these domains expressed independently have been solved.
      However, to date the three-dimensional structure remains unknown for full-length
      and even for any two domains together of any NHR family member. The available
      structures nevertheless begin to give clues of how site-specific DNA binding
      takes place, and how ligand binding alters the ligand-binding domain,
      consequently affecting potential interactions of the NHRs with co-activators/co
      repressors and other components of basal transcriptional machinery. However,
      precisely how signals from a ligand through its NHR are passed to specific genes
      is still unknown. Herein, we present a broad overview of current knowledge on the
      structure and functions of the NHRs.

PMID- 15242338
TI  - Role of molecular chaperones in steroid receptor action.
AB  - Unliganded steroid receptors are assembled into heterocomplexes with heat-shock
      protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding
      the receptors at the chaperone site, hsp90 binds cofactors at other sites that
      are part of the assembly machinery, as well as immunophilins that connect the
      assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The
      hsp90-/hsp70-based chaperone machinery interacts with the unliganded
      glucocorticoid receptor to open the steroid-binding cleft to access by a steroid,
      and the machinery interacts in very dynamic fashion with the liganded,
      transformed receptor to facilitate its translocation along microtubular highways
      to the nucleus. In the nucleus, the chaperone machinery interacts with the
      receptor in transcriptional regulatory complexes after hormone dissociation to
      release the receptor and terminate transcriptional activation. By forming
      heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to
      degradation by the ubiquitin-proteasome pathway of proteolysis.

PMID- 15242339
TI  - DNA recognition by nuclear receptors.
AB  - The nuclear receptors constitute a large family of ligand-inducible transcription
      factors. The control of many genetic pathways requires the assembly of these
      nuclear receptors in defined transcription-activating complexes within control
      regions of ligand-responsive genes. An essential step is the interaction of the
      receptors with specific DNA sequences, called hormone-response elements (HREs).
      These response elements position the receptors, and the complexes recruited by
      them, close to the genes of which transcription is affected. HREs are bipartite
      elements that are composed of two hexameric core half-site motifs. The identity
      of the response elements resides in three features: the nucleotide sequence of
      the two core motif half-sites, the number of base pairs separating them and the
      relative orientation of the motifs. The DNA-binding domains of nuclear receptors
      consist of two zinc-nucleated modules and a C-terminal extension. Residues in the
      first module determine the specificity of the DNA recognition, while residues in
      the second module are involved in dimerization. Indeed, nuclear receptors bind to
      their HREs as either homodimers or heterodimers. Depending on the type of
      receptor, the C-terminal extension plays a role in sequence recognition,
      dimerization, or both. The DNA-binding domain is furthermore involved in several
      other functions including nuclear localization, and interaction with
      transcription factors and co-activators. It is also the target of post
      translational modifications. The DNA-binding domain therefore plays a central
      role, not only in the correct binding of the receptors to the target genes, but
      also in the control of other steps of the action mechanism of nuclear receptors.

PMID- 15242340
TI  - Transcriptional activation by nuclear receptors.
AB  - Transcriptional activation by nuclear receptors (NRs) involves the recruitment of
      distinct classes of co-activators and other transcription-related factors to
      target promoters in the chromatin environment of the nucleus. Chromatin has a
      general repressive effect on transcription, but also provides opportunities for
      NRs to regulate transcription by directing specific patterns of chromatin
      remodelling and histone modification. Ultimately, the transcription of hormone
      regulated genes by NRs is critically dependent on co-ordinated physical and
      functional interactions among the receptors, chromatin, co-activators with
      chromatin-, histone- and factor-modifying activities, and the RNA polymerase II
      transcriptional machinery. In addition, several mechanisms exist to terminate or
      attenuate NR-dependent signalling, including modification, recycling, subcellular
      redistribution and degradation of the receptors or their associated cofactors.
      The complexity of NR-dependent transcription provides multiple targets for
      regulatory inputs, thus allowing each hormone-responsive cell to direct its
      transcriptional output in a physiologically appropriate manner.

PMID- 15242341
TI  - Gene repression by nuclear hormone receptors.
AB  - Repression by nuclear hormone receptors (NHRs) plays an important role in
      development, immune response and cellular function. We review mechanisms of how
      NHRs act as repressors of gene transcription either by direct contact with basal
      transcription factors or through recruitment of cofactors and enzymic activities
      that modulate chromatin accessibility. We describe also the role and biochemical
      mechanism of the cognate hormone that switches a NHR from a transcriptional
      silencer into an activator. This includes data from crystal structure, functional
      receptor domain analyses and the role of co-repressors in chromatin modification
      and remodelling. Furthermore, the comparison of negative response elements with
      classical response elements unravels the role of co-repressors in this context.
      We also describe the inhibition of the nuclear factor kappaB and Jun/Fos pathway
      by NHRs, as well as the molecular mechanism of anti-hormone therapies. Anti
      hormones are commonly used in breast and prostate cancer therapy to inhibit
      cancer proliferation through repression of the oestrogen or androgen receptor,
      respectively. Here we provide a comprehensive overview of the various mechanism
      of NHR repression.

PMID- 15242342
TI  - Receptor mechanisms of rapid extranuclear signalling initiated by steroid
      hormones.
AB  - In addition to their role as direct regulators of gene transcription mediated by
      classical nuclear hormone receptors, steroid hormones have also been described to
      exert rapid effects on intracellular signalling pathways independent of gene
      transcription. This chapter focuses on recent advances in our understanding of
      the receptors and mechanisms that mediate these rapid signalling actions of
      oestrogens and progesterone. Increasing evidence suggests that at least some of
      these rapid actions are mediated by a subpopulation of the classical nuclear
      oestrogen receptor (ER) and progesterone receptor (PR) that localize to the
      cytoplasm or associate with the plasma membrane. Human PR has been shown to
      mediate rapid progestin activation of the Src/Ras/Raf/mitogen-activated protein
      kinase signalling pathway in mammalian cells by a direct interaction with the Src
      homology 3 domain of Src tyrosine kinases through a Pro-Xaa-Xaa-Pro-Xaa-Arg motif
      located in the N-terminal domain of the receptor. Moreover, this is an
      extranuclear action of PR that is separable from its direct transcriptional
      activity. Additionally, a novel membrane protein unrelated to nuclear PR was
      recently identified that has properties of a G-protein-coupled receptor for
      progesterone and has been shown to be involved in mediating the extranuclear
      signalling actions of progesterone that promotes oocyte maturation in fish. The
      role of this membrane PR (mPR) in mammalian cells is less clear and the
      relationship of the membrane and classical nuclear PR in mediating rapid non
      transcriptional signalling of progestins has not been explored. To date, a novel
      membrane ER unrelated to classical nuclear receptors has not been cloned and
      characterized, and many of the known rapid extranuclear signalling actions of
      oestrogen appear also to be mediated by a subpopulation of nuclear ER, or a
      closely related receptor. A novel protein termed modulator of non-genomic
      activity of ER (MNAR) has been identified that acts as an adaptor between ER and
      Src, and thus provides a mechanisms for coupling of oestrogen and ER with rapid
      oestrogen-induced activation of Src and the downstream mitogen-activated protein
      kinase signalling cascade. The physiological relevance of rapid extranuclear
      signalling by the classical ER has been provided by experiments showing that
      these actions contribute to the anti-apoptotic effect of oestrogen in bone in
      vivo and to the rapid effects of oestrogen on vasodilation and protection of
      endothelial cells against injury.

PMID- 15242343
TI  - Nuclear receptors and disease: androgen receptor.
AB  - The death of cells by apoptosis is a fundamental event in development and the
      maintenance of cell homoeostasis. The other side of the coin, however, is that
      excessive cell death by apoptosis or the lack of apoptosis is often the driving
      force of many diseases. Whereas reduced apoptosis sensitivity is a basic
      characteristic of many tumour cells, accelerated tissue cell death and loss of
      tissue functions is the underlying cause of many auto-immune and inflammatory
      diseases.

PMID- 15242344
TI  - Glucocorticoid and mineralocorticoid receptors and associated diseases.
AB  - Adrenal corticosteroids, i.e. glucocorticoids and mineralocorticoids, play
      important physiological roles in humans. Their actions are mediated by
      intracellular receptor molecules, the glucocorticoid receptor (GR) and
      mineralocorticoid receptor (MR), which function as hormone-dependent
      transcription factors. Ligand-activated receptors modulate the transcription
      rates of responsive genes by interacting with responsive elements in the
      promoters of these genes or by influencing the activities of other transcription
      factors, via protein-protein interactions. Natural inactivating mutations of the
      GR or MR genes have been reported in humans with significant clinical phenotypes.
      The former causes sporadic or familial glucocorticoid resistance characterized by
      generalized partial insensitivity of tissues to glucocorticoids and subsequent
      activation of the hypothalamic/pituitary/adrenal axis with resultant
      hyperandrogenism in children and women and/or mineralocorticoid excess symptoms
      in both sexes. The latter develop pseudohypoaldosteronism type 1, i.e.
      hypotension and hyperkalaemic acidosis, as a result of reduced aldosterone
      actions in the kidney. An activating mutation in the MR gene causing early-onset,
      periodic hypertension was reported recently. The biological relevance of the GR
      and MR receptors was also addressed in mice whose GR or MR genes were inactivated
      or modified by gene targeting. The results were generally confirmatory of the
      concepts obtained by the human studies. Similarly, natural, compensated
      glucocorticoid and/or mineralocorticoid 'resistance' were described in several
      mammalian species, including non-human primates and rodents. Here we discuss the
      actions of GR and MR and the molecular defects of naturally occuring mutations in
      these receptors with associated pathophysiological changes.

PMID- 15242345
TI  - Nuclear receptors in disease: the oestrogen receptors.
AB  - For several decades, it has been known that oestrogens are essential for human
      health. The discovery that there are two oestrogen receptors (ERs), ERalpha and
      ERbeta, has facilitated our understanding of how the hormone exerts its
      physiological effects. The ERs belong to the family of ligand-activated nuclear
      receptors, which act by modulating the expression of target genes. Studies of ER
      knockout (ERKO) mice have been instrumental in defining the relevance of a given
      receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest
      diseases in which dysfunctional ERs might be involved in aetiology and pathology.
      Association between single-nucleotide polymorphisms (SNPs) in ER genes and
      disease have been demonstrated in several cases. Selective ER modulators (SERMs),
      which are selective with regard to their effects in a certain cell type, already
      exist. Since oestrogen has effects in many tissues, the goal with a SERM is to
      provide beneficial effects in one target tissue while avoiding side effects in
      others. Refined SERMs will, in the future, provide improved therapeutic
      strategies for existing and novel indications.

PMID- 15242346
TI  - Nuclear receptors in disease: thyroid receptor beta, peroxisome-proliferator
      activated receptor gamma and orphan receptors.
AB  - The nuclear receptor superfamily comprises a group of proteins that includes the
      molecular targets for classical steroid hormones such as glucocorticoids,
      androgens and vitamin D, together with a number of so-called 'orphan' receptors
      whose ligands and/or function remain to be determined. Many of the world's most
      commonly prescribed drugs act via nuclear receptors, attesting to their
      importance as therapeutic targets in human disease [for example, the novel anti
      diabetic thiazolidinediones rosiglitazone and pioglitazone are high-affinity
      ligands for peroxisome-proliferator-activated receptor gamma (PPARgamma)]. The
      study of transgenic mice harbouring global and tissue-specific alterations in
      nuclear receptor genes has greatly enhanced our understanding of the roles that
      these receptors play in mammalian physiology. In many cases, these findings have
      been complemented by the study of human subjects harbouring naturally occurring
      mutations within the corresponding receptor, whereas in others, such studies have
      served to highlight important differences that exist between human and mouse
      physiology especially, for example, in relation to aspects of metabolism. Here we
      review the diverse clinical phenotypes that have been reported in subjects found
      to have germline mutations in thyroid hormone receptor beta, PPARgamma,
      hepatocyte nuclear factor 4alpha, small heterodimer partner, steroidogenic factor
      1, DAX1, photoreceptor-specific nuclear receptor and NUR-related factor 1, and
      consider the molecular mechanisms through which aberrant signalling by mutant
      receptors might contribute to the pathogenesis of the associated disorders.

PMID- 15242347
TI  - A crustacean Ca2+-binding protein with a glutamate-rich sequence promotes CaCO3
      crystallization.
AB  - The DD4 mRNA of the penaeid prawn Penaeus japonicus was shown previously to be
      expressed in the epidermis adjacent to the exoskeleton specifically during the
      post-moult period, when calcification of the exoskeleton took place. The encoded
      protein possessed a Ca2+-binding site, suggesting its involvement in the
      calcification of the exoskeleton. In the present study, an additional ORF (open
      reading frame) of 289 amino acids was identified at the 5' end of the previous
      ORF. The newly identified part of the encoded protein included a region of
      approx. 120 amino acids that was highly rich in glutamate residues, and contained
      one or more Ca2+-binding sites. In an immunohistochemical study, signals were
      detected within calcified regions in the endocuticular layer of the exoskeleton.
      Bacterially expressed partial segments of the protein induced CaCO3
      crystallization in vitro. Finally, a reverse transcription-PCR study showed that
      the expression was limited to an early part of the post-moult period, preceding
      significant calcification of the exoskeleton. These observations argue for the
      possibility that the encoded protein, renamed crustocalcin (CCN), promotes
      formation of CaCO3 crystals in the exoskeleton by inducing nucleation.

PMID- 15242348
TI  - Inositol phospholipids regulate the guanine-nucleotide-exchange factor Tiam1 by
      facilitating its binding to the plasma membrane and regulating GDP/GTP exchange
      on Rac1.
AB  - Binding of the Rac1-specific guanine-nucleotide-exchange factor, Tiam1, to the
      plasma membrane requires the N-terminal pleckstrin homology domain. In the
      present study, we show that membrane-association is mediated by binding of
      PtdIns(4,5)P(2) to the pleckstrin homology domain. Moreover, in 1321N1
      astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor
      mediated stimulation of PtdIns(4,5)P(2) breakdown, correlates with decreased Rac1
      GTP levels, indicating that membrane-association is required for GDP/GTP exchange
      on Rac1. In addition, we show that platelet-derived growth factor activates Rac1
      in vivo by increasing PtdIns(3,4,5)P(3) concentrations, rather than the closely
      related lipid, PtdIns(3,4)P(2). Finally, the data demonstrate that
      PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) bind to the same pleckstrin homology domain
      in Tiam1 and that soluble inositol phosphates appear to compete with lipids for
      this binding. Together, these novel observations provide strong evidence that
      distinct phosphoinositides regulate different functions of this enzyme,
      indicating that local concentrations of signalling lipids and the levels of
      cytosolic inositol phosphates will play crucial roles in determining its activity
      in vivo.

PMID- 15242349
TI  - Tetracycline-regulated expression enables purification and functional analysis of
      recombinant connexin channels from mammalian cells.
AB  - Intercellular coupling mediated by gap junction channels composed of connexin
      protein underlies numerous physiological processes, such as cellular
      differentiation, tissue synchronization and metabolic homoeostasis. The distinct
      molecular permeability of junctional channels composed of different connexin
      isoforms allows cellular control of coupling via regulation of isoform
      expression. However, the permeability properties of most connexin isoforms have
      not been well characterized due to the difficulty of manipulating and measuring
      the diffusible concentrations of cytoplasmic messenger molecules and metabolites,
      and to a lack of control over channel isoform composition, in vivo. Here we
      present a method to express and purify active connexin hemichannels of a single
      isoform or a consistent ratio of two isoforms from cultured cells using the Tet
      On inducible expression system and one-step anti-haemagglutinin immunoaffinity
      purification. The procedure yields 10-20 microg of pure connexin protein from
      2.5x10(8) HeLa cells. The purified channels are shown to be useful for in vitro
      permeability analysis using well established techniques. This method has
      substantial advantages over existing methods for heterologous connexin
      expression, such as the ease of co-expression of two isoforms at a constant
      ratio, consistently high expression levels over many passages, and the ability to
      study channel properties in situ as well as in purified form. Furthermore, the
      generic cloning site of the new pBI-GT vector and the commercial availability of
      anti-haemagglutinin (clone HA-7)-agarose make this affinity tagging and
      purification procedure easily applicable to other proteins.

PMID- 15242351
TI  - Laparoscopic pyeloplasty for ureteropelvic junction obstruction: outcome of
      initial 12 procedures.
AB  - BACKGROUND: Open pyeloplasty has been the gold standard for surgical treatment of
      ureteropelvic junction (UPJ) obstruction, enjoying a long-term success rate
      exceeding 90%. Unfortunately, this procedure requires a muscle incision that
      entails some degree of morbidity. We have, therefore, investigated the
      feasibility of laparoscopic pyeloplasty for UPJ obstruction and report here the
      outcomes of our early cases. The median follow up is 25 months (range, 12-42
      months). METHODS: Between March 1999 and September 2001 we performed laparoscopic
      pyeloplasty on 12 ureters in 11 patients presenting with symptomatic
      hydronephrosis, secondary to a short stenosis of the UPJ or to ventrally crossing
      vessels; bilateral pyeloplasty was performed as a single procedure in one
      patient. We performed dismembered Anderson-Hynes pyeloplasty, Fenger plasty and Y
      V plasty in eight, two and two ureters, respectively. All procedures were carried
      out transperitoneally. RESULTS: The procedure was completed successfully in all
      cases. Crossing vessels were noted in six of 12 ureters (50.0%). Mean operative
      time and blood loss in 11 patients (including one bilateral case) were 272.8 min
      (range, 175-480 min) and 96.4 mL (range, 20-340 mL), respectively. Postoperative
      complications were noted in two patients (18.2%): one instance of prolonged urine
      leakage and one anastomotic re-stricture. Eleven of 12 ureters (91.6%)
      demonstrated a patent UPJ on excretory urography and/or improvement of renal
      function on diuretic renography at a minimum follow up of 12 months. CONCLUSION:
      Although the procedure requires advanced laparoscopic skills, it can be safely
      and successfully completed as frequently as the conventional open procedure.
      Laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty
      for UPJ obstruction.

PMID- 15242350
TI  - Upstream stimulatory factors, USF1 and USF2, bind to the human haem oxygenase-1
      proximal promoter in vivo and regulate its transcription.
AB  - The human HO-1 (haem oxygenase-1) gene encodes a microsomal enzyme responsible
      for the breakdown of haem, and is also cytoprotective in response to various
      cellular insults. HO-1 transcription is induced by a vast array of compounds
      including, but certainly not limited to, haem and heavy metals such as cadmium.
      In the present study, we show that upstream stimulatory factors, USF1 and USF2,
      ubiquitous proteins belonging to the basic helix-loop-helix-leucine zipper family
      of transcription factors, constitutively bind to the class B E-box located in the
      proximal promoter of the human HO-1 gene and are responsible for the enhancement
      of HO-1 gene transcription in human renal proximal tubular epithelial cells.
      Dimethylsulphate in vivo footprinting studies have identified three protected
      guanine residues in the E-box of the HO-1 proximal promoter. One of these guanine
      contact points is essential for USF binding, and when mutated mimics a deletion
      mutation of the entire E-box palindrome sequence encompassing all three guanine
      contact points. Binding of USF1 and USF2 to the HO-1 E-box was confirmed by
      chromatin immunoprecipitation and gel-shift assays. Furthermore, we show that
      overexpression of USF1 or USF2 enhances the basal expression of HO-1 and that
      expression of a USF dominant negative form reduces its expression. These results
      demonstrate for the first time that USF proteins bind to the human HO-1 promoter
      in vivo and are required for high-level expression of HO-1 by haem and cadmium in
      human renal epithelial cells.

PMID- 15242352
TI  - Impact of adjuvant systemic chemotherapy on postoperative survival in patients
      with high-risk urothelial cancer.
AB  - BACKGROUND: The objective of this study was to retrospectively investigate the
      effectiveness of adjuvant combination chemotherapy for locally advanced
      urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally
      advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological
      stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical
      nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph
      node-positive disease and 25 patients did not. Twenty patients underwent adjuvant
      chemotherapy and 36 patients were observed after surgery. Cox proportional
      hazards models were used to determine the impact of numerous clinicopathological
      findings on survival. A subgroup analysis of patients with lymph node-positive
      disease was conducted to evaluate disease-free survival and overall survival
      rates. RESULTS: In this series, the median follow-up period was 39 months (range,
      4-163) after surgery. Disease-free and overall survival rates of all 56 patients
      were 45% and 58%, respectively, at 3 years. Only lymph node status was
      significantly associated with disease-free and overall survival in the
      multivariate analyses. In a subgroup analysis of patients with lymph node
      positive disease, 16 patients who underwent adjuvant chemotherapy had superior
      disease-free survival compared to 15 patients with no adjuvant chemotherapy (P =
      0.0376). CONCLUSION: These findings show that the prognosis of advanced
      urothelial cancer is significantly associated with nodal status. Furthermore,
      adjuvant combination chemotherapy has a positive impact on survival in patients
      with lymph node-positive disease.

PMID- 15242353
TI  - Our experience with 23 consecutive patients on gemcitabine/carboplatin
      chemotherapy for treatment of metastasized transitional cell carcinoma of the
      urothelium.
AB  - AIM: To evaluate the activity and toxicity of gemcitabine plus carboplatin in
      patients with metastatic transitional cell carcinoma (TCC) of the urothelium.
      METHODS: Twenty-three consecutive patients (from February 1999 to January 2002)
      with metastatic TCC and no prior chemotherapy were referred to our institution.
      Each patient was treated with gemcitabine (1000 mg/m2) on Days 1 and 8 and
      carboplatin (area under curve, 4.5) on Day 1. Cycles were repeated every 21 days
      until tumor progression or severe toxicity was seen, or for a maximum of six
      cycles. Median age of the patients was 68 years (range 47-82). The median Eastern
      Cooperative Oncology Group (ECOG) performance score was one and the median
      creatinine clearance rate was 56 mL/min (range 31-94). RESULTS: The overall
      response rate was 60.8%, with five of the 23 patients achieving a complete
      response, and nine showing a partial response. Median time to tumor progression
      (TTP) was 7.8 months, with a median survival of 15.4 months and a 1-year survival
      probability of 56%. Most of the complications from toxicity were hematological.
      CONCLUSIONS: Gemcitabine plus carboplatin is active in the treatment of
      metastatic urothelial cancer in those patients new to chemotherapy and has an
      acceptable safety profile. The potential clinical benefit of this novel
      combination in the treatment of transitional cell carcinoma warrants further
      testing in Phase III studies.

PMID- 15242354
TI  - Histopathological aspects of transitional cell carcinoma of the bladder: analysis
      of 20 years experience.
AB  - BACKGROUND: In this study we used histopathological examinations performed over a
      20-year period to describe the characteristics of newly diagnosed transitional
      cell carcinoma (TCC) of the bladder in relation to patient age, and to verify
      changes in the TCC over different periods of observation or in relation to
      patient age. METHODS: We reviewed all histopathological examinations performed
      from January 1979 to December 1998 in patients undergoing surgery who were newly
      diagnosed with TCC of the bladder. All examinations were performed by the same
      pathologist and reviewed by two pathologists. In each case analyzed, we evaluated
      T classification of the tumor, histological grade, size, localization, growth
      type, multiplicity and carcinoma in situ (CIS). RESULTS: The study population
      included 3113 men and 620 women. The mean patient age was 66.31 +/- 10.84 years.
      A high percentage of Ta (52.2%) and T1 (27.7%) tumors were found. The number of
      cases observed and, in particular, the percentage of Ta tumors increased
      significantly and progressively from the first (1979-1983 = 376 cases; Ta =
      37.8%) to the last (1994-1998 = 1732 cases; Ta = 56.3%) period of observation (P
      < 0.001). A significant difference in the distribution of histological grade and
      T classification in the different age decades was apparent (P < 0.001); in
      particular, for G1 and Ta tumors there was a trend to decrease, whereas for G3,
      T1 and T2 tumors there was a tendency to increase with age decades. CONCLUSION:
      In our analysis, age of patient and the period of examination significantly
      influenced different pathological characteristics of newly diagnosed TCC of the
      bladder.

PMID- 15242355
TI  - Clinical study of bladder cancer: Proteinuria as a predictor of recurrence and
      efficacy of intravesical bacille Calmette-Guerin therapy.
AB  - AIM: We studied the clinical characteristics of bladder cancer, with special
      attention to the clinical and pathological variables that affect tumor stage,
      relapse and efficacy of intravesical therapy. METHODS: We reviewed the medical
      records of 152 patients of the Saiseikai Central Hospital who had been diagnosed
      as having bladder cancer between 1981 and 2001. RESULTS: The age of the patients
      ranged from 24 to 88 years, with a median of 63.5 years. The median follow up was
      52.4 months (range, 0.5-259.5 months). There was no difference in the incidence
      of gross hematuria as a presenting symptom among the patients with invasive
      cancer, superficial cancer and carcinoma in situ (CIS). However, the incidence of
      urinary frequency and painful urination did differ significantly between
      patients. Although patients with invasive cancer had a longer time to hospital
      visit than those with superficial cancer, this time difference was not
      statistically significant. Presence of proteinuria, multifocality and
      intravesical bacille Calmette-Guerin (BCG) therapy were the significant
      predictors of relapse after transurethral resection (TUR). Presence of
      proteinuria was shown to adversely affect the efficacy of intravesical BCG
      therapy. In the BCG-treated group, 3-year relapse-free survival was 78.4% for
      patients without proteinuria and 40.0% for those with proteinuria; this
      difference was statistically significant (P = 0.0277). CONCLUSIONS: Time to
      hospital visit did not influence the pathological stage of cancer in patients
      included in the present study. Presence of proteinuria, multifocality and BCG
      therapy were the significant predictors of relapse after TUR. Presence of
      proteinuria was shown to adversely affect the efficacy of intravesical BCG
      therapy. Proteinuria might be helpful in predicting tumor relapse and efficacy of
      intravesical BCG therapy in clinical settings, along with other markers.

PMID- 15242356
TI  - Complications of laparoscopic radical cystectomy during the initial experience.
AB  - AIM: Radical cystectomy is the standard of care for patients with muscle invasive
      bladder cancer. While open radical cystectomy is now a standard procedure,
      laparoscopic radical cystectomy is still in its infancy. We performed this
      surgery laparoscopically in 11 patients and review the procedure specific
      complications. METHODS: Beginning in February 1999, 11 patients underwent
      laparoscopic radical cystectomy at the Department of Urology, All India Institute
      of Medical Sciences, New Dehli. Urinary diversion was performed by an open-hand
      sewn ileal conduit. RESULTS: There were three intraoperative complications
      specifically related to the laparoscopic radical cystectomy. These included
      injury to the external iliac vein in one patient and a small rectal tear in two.
      All were repaired with laparoscopic free hand suturing with normal postoperative
      recovery. Other laparoscopy-related complications were subcutaneous emphysema in
      one patient and hypercarbia necessitating conversion to open surgery in a patient
      who, four weeks after surgery, died of multiple organ failure. One patient had
      margins positive and received cisplatinum-based chemotherapy. All patients had
      normal renal function and preserved upper tracts with no evidence of metastasis
      at a mean of 18.4 months follow up (range 1-48 months). CONCLUSIONS: Though there
      were three complications specific to the laparoscopic radical cystectomy, none
      necessitated a conversion to open surgery or hampered the overall outcome.
      Absence of local recurrence or metastatic disease at four years of follow up
      suggests that the procedure is oncologically valid. Laparoscopic radical
      cystectomy is a new procedure and it is important to critically analyze the
      complications in order to reduce their occurrence and allow the development of a
      better technique.

PMID- 15242357
TI  - Influence of pain and urinary symptoms on quality of life in young men with
      chronic prostatitis-like symptoms.
AB  - BACKGROUND: Our aims in the present study were to estimate the influences of pain
      and urinary symptoms on quality of life, and to determine which of these two
      variables has the most predictive power with respect to quality of life in young
      men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like
      symptoms were measured by the National Institutes of Health-Chronic Prostatitis
      Symptom Index. Of the 28,841 men aged 20 years who lived in the study community,
      18,495 men (a response rate 64.1%) agreed to participate in the study. A total of
      1057 men who complained of symptoms indicative of chronic prostatitis were
      included in the study. The influences of pain and urinary symptoms on quality of
      life were determined using logistic regression analysis. The receiver operating
      characteristic (ROC) curve was used to estimate the predictive ability of each of
      these variables with respect to quality of life. RESULTS: Results from
      multivariate analysis showed that both pain and urinary symptoms were associated
      with an increased likelihood of impaired quality of life, although pain
      contributed more to a reduced quality of life than urinary symptoms. Relative to
      men who experienced mild pain, men who experienced moderate pain had a 3.9-fold
      risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval
      [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold
      risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001).
      Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR,
      1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated
      with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild
      urinary symptoms. Comparison of the effects of pain and urinary symptoms showed
      that pain severity had the most predictive power for bother, quality of life, and
      quality-of-life impact. The areas under the ROC curves for bother, quality of
      life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively.
      CONCLUSION: Urinary symptoms and pain might be associated with an increased
      likelihood of impaired quality of life in young men with chronic prostatitis-like
      symptoms. In addition, our findings suggest that pain severity is the most
      influential variable for determining quality of life in this population.

PMID- 15242358
TI  - Effectiveness of percent free prostate specific antigen as a predictor of
      prostate cancer detection on repeat biopsy.
AB  - BACKGROUND: The aim of this study was to identify predictors that can increase
      the accuracy of detecting prostate cancer on subsequent biopsies. METHODS:
      Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA)
      levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies
      of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26
      (11.1%) underwent two or more repeat biopsies. We evaluated the results of
      prostate biopsies in relation to the morbidity of prostate cancer detected on
      repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%)
      had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or
      more repeat biopsies, and five of these patients were found to have early stage
      prostate cancer. On repeat biopsy, there was a significant difference in percent
      free PSA between the cancer-detected group and the no-cancer-detected group (P <
      0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off
      value for percent free PSA of 11%, demonstrating a significant difference in the
      cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re
      biopsies showed that cancer-detected cases showed a raised PSA value and a
      simultaneously reduced percent free PSA (these differences were statistically
      significant). CONCLUSIONS: A low percent free PSA level increased the probability
      of a positive result in repeat biopsy. An increase in the accuracy of detecting
      cancer, especially on repeat biopsy, will promote the detection of more early
      stage prostate cancer.

PMID- 15242360
TI  - The trend of managing prostate cancer in Taiwan.
AB  - BACKGROUND: The purpose of this study is to investigate the current trends of
      Taiwanese urologists in managing prostate cancer (CaP). This will help us to
      establish our own consensus and recommend appropriate treatment options to the
      related patients. METHODS: From November 2000 to April 2001, a questionnaire
      concerning the alertness of detecting CaP, diagnostic tools used for establishing
      the staging of CaP before radical surgery, the tolerated age for surgery and the
      use of hormone therapy for advanced CaP was mailed to the 465 urologists in
      active practice in the Taiwan area. RESULTS: A total of 240 (51.6%) physicians
      responded to our questionnaire. 89.1% of the respondents would add serum
      prostatic-specific antigen (PSA) to detect suspected malignancy during the work
      up for benign prostatic hyperplasia in their daily practice. About three quarters
      of the respondents adopted free/total PSA in assisting the decision for prostate
      biopsy. 78% require a bone scan before radical surgery even when PSA is less than
      10 ng/mL and the age tolerated for radical surgery is 75 years. 60.8% still
      believed that maximal androgen blockade is effective for advanced CaP.
      CONCLUSIONS: The trend of treating CaP provides a useful insight into the
      variations in clinical practice of Taiwanese urologists and may help to develop a
      more widely accepted guideline by our urological community.

PMID- 15242359
TI  - Single-blind, randomized controlled study of the clinical and urodynamic effects
      of an alpha-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment
      of benign prostatic hyperplasia.
AB  - AIM: The aim of our study was to examine the efficacy of naftopidil in terms of
      the international prostate symptom score (IPSS) and urodynamic parameters in the
      treatment of benign prostatic hyperplasia (BPH). Eviprostat was used as a control
      to study the efficacy of naftopidil. METHODS: Forty-nine patients with BPH (mean
      age 67.9 +/- 7.8 years) were involved in the study. Patients were randomly
      assigned either to the naftopidil group, which was treated with the alpha-blocker
      naftopidil (50-75 mg daily, 36 patients), or the eviprostat group, which was
      treated with phytotherapy (six tablets of eviprostat daily, 13 patients).
      RESULTS: The mean total IPSS, the total storage and voiding symptom scores, and
      the quality of life score decreased significantly (P < 0.0001 for each variable)
      in the naftopidil group, but not in the eviprostat group. In the naftopidil
      group, analyses showed significant increases in average and maximum flow rate and
      bladder capacity at first desire to void (P < 0.001, P = 0.001 and P = 0.024,
      respectively), and significant decreases in the postvoid residual, the percent of
      residual and the Abrams-Griffiths number (P = 0.009, P = 0.008 and P = 0.042,
      respectively). However, in the eviprostat group, no significant changes were
      noted in terms of these symptomatic and urodynamic parameters. In the
      pressure/flow study, an improvement in the International Continence Society
      nomogram grade was noted in 29% of the naftopidil group, but in only 16% of the
      eviprostat group. Among the 14 patients in the naftopidil group, detrusor
      overactivity disappeared in 21% and cystometric capacity increased in 36%, but no
      improvement in detrusor overactivity was noted in the eviprostat group.
      CONCLUSIONS: Naftopidil appears to have been effective in this short-term
      treatment of BPH.

PMID- 15242362
TI  - The etiology of erectile dysfunction and contributing factors in different age
      groups in Turkey.
AB  - BACKGROUND: The aim of the present study was to determine the pathophysiological
      factors which cause erectile dysfunction (ED), as well as the risk factors in
      different age groups in Turkey. METHODS: A total of 948 patients with ED who were
      admitted to three andrology clinics were evaluated in terms of etiological
      factors. They underwent a multidisciplinary diagnostic evaluation. Erectile
      dysfunction was classified as primarily organic, primarily psychogenic, mixed or
      unknown in etiology. RESULTS: Psychogenic ED was diagnosed in 65.4% of the
      patients and organic ED was diagnosed in 34.6% of patients overall. In patients
      under 40 years, the rate of psychogenic ED was 83% and the rate of organic ED was
      17%, but in the patients over 40 years, the rate of psychogenic ED was 40.7% and
      the rate of organic ED was 59.3%. The causes of organic ED were identified as
      arteriogenic ED, 40.5%; cavernosal factor (venogenic) ED, 10%; neurogenic ED,
      12.5%; endocrinologic ED, 1.8%; mixed type ED, 11.8%; and drug induced ED, 4.5%.
      CONCLUSION: Our data represent a higher ratio of ED in patients under 40, which
      are mostly psychogenic, This finding potentially results from local social and
      cultural differences.

PMID- 15242361
TI  - Safety and efficacy of vardenafil in patients with erectile dysfunction: result
      of a bridging study in Japan.
AB  - AIM: Vardenafil is a selective and highly potent phosphodiesterase type 5 (PDE5)
      inhibitor for the treatment of erectile dysfunction (ED), with improved
      selectivity for PDE5 and demonstrated efficacy for improving sexual function in
      men with ED. The current study investigated the safety and efficacy of this new
      PDE5 inhibitor in Japanese men with ED. METHODS: This was a prospective, double
      blind, randomized clinical trial designed to evaluate the efficacy and safety of
      vardenafil. Following a 4-week treatment-free observation period, 283 eligible
      patients were randomized to 12 weeks treatment with vardenafil 5 mg, 10 mg, 20
      mg, or placebo. Primary efficacy responses were assessed using the scores of Q3
      and Q4 of the international index of erectile function (IIEF). RESULTS: All three
      vardenafil doses showed significantly better improvement than the placebo group
      in Q3 and Q4 scores of the IIEF questionnaire, either at 12 weeks or at the 'last
      observation carried forward' (LOCF, P < 0.0001). Q3 scores were improved to 4.06
      with vardenafil 5 mg, 4.53 with vardenafil 10 mg, and 4.64 with vardenafil 20 mg,
      versus 3.17 with placebo. Comparable scores for Q4 were 3.47, 4.15 and 4.31
      versus 2.31 for placebo. Up to 86% of patients achieved improved erections as
      assessed by the global assessment question (GAQ). Reported adverse event rates
      were 35.3%, 45.3% and 54.5% with vardenafil 5 mg, 10 mg and 20 mg, respectively,
      versus 21.1% in the placebo group. No serious adverse drug reactions were
      reported. The most common treatment-emergent adverse events were transient
      headache, flushing and rhinitis, which were mostly mild. CONCLUSION: Vardenafil
      is an effective and well-tolerated treatment for ED and provides improvement in
      key indices of erectile function among Japanese men with ED. The results of our
      trial show that up to nearly 90% of patients achieve improved erections with the
      administration of vardenafil.

PMID- 15242363
TI  - Erectile dysfunction in hemodialysis patients with diabetes mellitus: association
      with age and hemoglobin A1c levels.
AB  - AIM: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM)
      as well as those undergoing hemodialysis (HD). The purpose of this study is to
      investigate the frequency and severity of ED in HD patients with DM and those
      without DM. In addition, we examined the relationship between erectile function
      and several risk factors, including presence of DM and hemoglobin A1c levels in
      HD patients. METHODS: This study involved 180 patients on HD, including 66 HD
      patients with DM (DM-HD) and 114 patients without DM (non-DM-HD). We evaluated
      erectile function using an abridged five-item version of the international index
      of erectile function (IIEF-5). Logistic regression analysis was used to
      investigate the relationship between presence of ED and several risk factors.
      RESULTS: The total score of IIEF-5 in DM-HD patients (9.5 +/- 4.2) was
      significantly lower than in non-DM-HD patients (13.5 +/- 5.7). The prevalence of
      severe ED was 42.4% and 18.4% in DM-HD patients and non-DM-HD patients,
      respectively. Age, cardiovascular disease history, and DM were identified as
      independent risk factors for the presence of ED. Furthermore, age and elevated
      hemoglobin A1c levels were identified as independent risk factors for the
      presence of severe ED. CONCLUSION: DM-HD patients are more likely to have ED, and
      particularly severe forms of ED, than non-DM-HD patients. DM and elevated
      hemoglobin A1c levels were associated with the presence of ED or severe ED,
      respectively. Aging was identified as an independent factor in both ED and severe
      ED.

PMID- 15242364
TI  - Clinical parameters that predict histology of postchemotherapy retroperitoneal
      lymph node mass in testicular cancer.
AB  - BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of
      metastatic testicular cancers can be cured by chemotherapy followed by
      retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND
      confers no therapeutic benefit if the residual mass contains no viable cells.
      Therefore, to determine which parameters predict a patient's likelihood of having
      only necrosis in the residual mass, we retrospectively analyzed clinical
      parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from
      27 patients with metastatic testicular cancer were analyzed. The histology of the
      primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the
      patients with non-seminoma showed a normalization of tumor markers after
      chemotherapy. Analysis of clinical parameters included data for the initial
      histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal
      mass size, and the histology of the dissected RPLNs. RESULTS: Histological
      examination of dissected RPLNs showed residual tumor in 27% of seminoma patients
      and 38% of non-seminoma patients. In seminoma patients, no viable cells were
      found in all six patients with pretreatment lactate dehydrogenase (LDH) levels
      below 7.5 times the upper limit of normal, or in all five of the patients with
      postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable
      cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP)
      levels less than 2700 ng/mL, or in eight of nine patients with residual mass less
      than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment
      tumor marker levels are possible predictors for necrosis of the residual mass in
      testicular cancer patients.

PMID- 15242365
TI  - Health-related quality of life after chemotherapy for advanced germ cell tumors:
      a comparison of standard-dose and high-dose chemotherapy.
AB  - BACKGROUND: The objective of this study was to evaluate the health-related
      quality of life (HRQoL) in patients with germ cell tumors who received standard
      dose chemotherapy or high-dose chemotherapy combined with peripheral blood stem
      cell transplantation (PBSCT), and to compare the HRQoL of these patients with
      patients who had undergone surveillance therapy only. METHODS: Among the 102
      patients included in this study, 38 underwent standard-dose cisplatin-based
      combination chemotherapy alone, 24 received high-dose chemotherapy with PBSCT
      following standard-dose chemotherapy, and 40 underwent surveillance monitoring.
      HRQoL was evaluated using the SF-36 survey, which contains 36 questions that
      assess eight quality-of-life aspects, including physical functioning, role
      physical functioning, bodily pain, general health, vitality, social functioning,
      role-emotional functioning and mental health. RESULTS: The follow-up period of
      the surveillance group was significantly longer than that of the remaining two
      groups receiving chemotherapy; however, scale scores were not affected by the
      duration of follow up in either group. No significant difference was observed in
      any scale scores between the patients undergoing chemotherapy and those in the
      surveillance group. In comparison with the general population in the USA, social
      functioning in both the chemotherapy and surveillance groups was significantly
      lower, whereas vitality in these two groups was significantly higher. Patients
      undergoing standard-dose chemotherapy alone had a significantly higher score for
      mental health than those undergoing high-dose chemotherapy. However, there were
      no significant differences in the remaining seven scores, irrespective of the
      type of chemotherapy. CONCLUSIONS: Seven of the eight scale scores of HRQoL were
      favorable in patients who received chemotherapy or surveillance, and no
      significant difference was observed between these two groups. Moreover, with the
      exception of the mental health score, HRQoL was not significantly affected by the
      type of chemotherapy. Therefore, patients who received chemotherapy, including
      high-dose chemotherapy with PBSCT, seem to be generally satisfied with their
      overall HRQoL.

PMID- 15242366
TI  - Laparoscopic drainage of nocardial adrenal abscess in an HIV positive patient.
AB  - We report a rare case of a nocardial adrenal abscess in an HIV patient that
      underwent the first drainage of adrenal abscess by laparoscopy. Adrenal abscesses
      are exceedingly rare in adults and prove to be a diagnostic challenge.
      Laparoscopic adrenal exploration is both a diagnostic and therapeutic modality
      with low perioperative morbidity that should be considered in the management of
      indeterminate adrenal masses and abscesses.

PMID- 15242367
TI  - Resection of local recurrence of renal cell carcinoma in a hemodialysis patient 6
      years after radical nephrectomy.
AB  - Left radical nephrectomy was performed on a 39-year-old-man because of renal cell
      carcinoma (grade 1, clear cell and granular cell carcinoma: pT3b pN0 pM0), 6
      years after the beginning of hemodialysis. The second surgical intervention for
      local recurrence was performed 6 years after the first operation (grade 2 > 3,
      clear cell and granular cell carcinoma). This is the second published case report
      of the resection of a local recurrence of renal cell carcinoma after nephrectomy
      in a hemodialysis patient. Even after the curative operation, follow up for local
      recurrence should be continued in hemodialysis patients, especially for high
      stage renal cell carcinoma.

PMID- 15242368
TI  - Dexamethasone and interleukin-2 combination therapy for advanced renal cell
      carcinoma in a patient with paraneoplastic inflammatory syndrome.
AB  - Interleukin-2 (IL-2) in combination with dexamethasone was administered to a 48
      year-old man with renal cell carcinoma accompanied by paraneoplastic inflammatory
      syndrome, including progressive multiple lung metastases and inferior vena caval
      tumor thrombus. Although non-steroidal anti-inflammatory drugs had no apparent
      antipyretic effect on the systemic inflammatory syndrome, oral administration of
      dexamethasone achieved complete antipyresis and improved his quality of life.
      After a 4-week period of IL-2 treatment, regression of metastasized lesions was
      demonstrated despite concurrent oral administration of dexamethasone. Steroids
      might reduce the action of immunotherapeutic drugs, but in some cases,
      combination therapy can achieve both alleviation of the paraneoplastic syndrome
      and tumor shrinkage.

PMID- 15242369
TI  - Papillary renal cell carcinoma radiographically mimicking massive calcification.
AB  - A 53-year-old male was referred to the Department of Urology, Hokkaido Kouseiren
      Kutchan Kousei Hospital for a left renal mass incidentally found by computed
      tomography. The tumor was 29 mm in diameter and showed ring-like calcification
      and heterogeneous enhancement by the contrast medium. The patient underwent left
      partial nephrectomy after the diagnosis of left renal cell carcinoma. Contrary to
      the radiographic finding, there was no palpable calcified lesion in the
      macroscopic specimen. Histopathologically, the tumor showed features of papillary
      renal cell carcinoma with massive psammoma bodies which might have been the cause
      for mimicking radiographic calcification.

PMID- 15242370
TI  - Hydronephrosis due to ureteral endometriosis treated by transperitoneal
      laparoscopic ureterolysis.
AB  - Ureteral obstruction secondary to endometriosis is relatively uncommon. We
      present a 43-year-old multiparous woman who suffered from periodic left loin pain
      in the terminal period of her menstruation. Excretory urogram demonstrated left
      hydronephrosis and hydroureter and obstruction of the lower left ureter just
      inferior to the left sacroiliac joint without urolithiasis. An enhanced computed
      tomography scan showed soft tissue density mass around the left ureter at the
      level of the stenosis. She underwent transperitoneal laparoscopic ureterolysis
      and adhesiotomy of the left ureter under the diagnosis of ureteral endometriosis.
      Because blueberry spots were clearly observed on the pelvic brim, the fibrous
      tissue surrounded the ureter was removed with peritoneal bleeding spots.
      Histological examination of the surrounding tissue confirmed the ectopic
      endometriosis. Even though retroperitoneoscopy is frequently used for ureteral
      lesion, transperitoneal laparoscopy has an advantage for resection of ectopic
      endometriosis surrounding the ureter.

PMID- 15242371
TI  - Urinary schistosomiasis in a Japanese man.
AB  - A 29-year-old Japanese man with a history of travel to Africa visited the
      Department of Urology, Nara Medical University complaining of intermittent
      asymptomatic gross hematuria over a period of 30 months. As he was suspected of
      being infested with schistosomal parasites based on his past history of swimming
      in Malawi Lake during his stay in Egypt two years previously, we examined his
      urine microscopically for the presence of Schistosoma haematobium eggs and
      diagnosed him as having urinary schistosomiasis. Endoscopic examination revealed
      multiple small erythematous torose lesions on the right posterior wall of the
      urinary bladder. Since he was treated by oral administration of praziquantel
      every 6 h for 2 days (total daily dose of 2400 mg), a specific anthelmintic drug
      for schistosomiasis, the disease has been successfully kept under control without
      significant lesions in the bladder mucosa after the immediate disappearance of
      the eggs in his urine.

PMID- 15242372
TI  - Urethral 'recurrence' found 14 years after radical cystectomy.
AB  - We report a case of transitional cell urethral cancer diagnosed 14 years after
      radical cystectomy. Traditionally, in the postcystectomy setting, these cancers
      have been referred to as 'recurrences'. We review the biological models for the
      oncogenesis of these cancers and propose that they are typically a result of a
      field cancerization effect, rather than being derived from the same clone
      responsible for the original urothelial tumor.

PMID- 15242373
TI  - Simplified treatment of massive rectal bleeding following prostate needle biopsy.
AB  - Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound
      guided prostate biopsy, but it usually stops spontaneously. We report a case of
      life-threatening rectal bleeding following this procedure. Bleeding was
      controlled using an ordinary condom, which was successfully inflated in the
      rectum over the bleeding site.

PMID- 15242374
TI  - Urethral leiomyoma expressing estrogen receptors.
AB  - A case of urethral leiomyoma is presented. The patient was a 48-year-old female
      who was hospitalized with a 4-year history of a progressively enlarging urethral
      mass. Based on clinical diagnosis of benign urethral tumor, local excision was
      performed. Histological diagnosis was urethral leiomyoma and the tumor cells
      demonstrated immunoreactivity for estrogen receptors. We report our experience of
      a leiomyoma of the urethra expressing estrogen receptors.

PMID- 15242375
TI  - Spontaneous expulsion of a bullet via the urethra.
AB  - The rare clinical occurrence of the spontaneous passage of bullet which was not
      found during an operation after a gunshot wound to the bladder in a 28-year-old
      man is described.

PMID- 15242376
TI  - Acute scrotum caused by Henoch-Schonlein purpura.
AB  - A boy aged 3 years and 11 months with arthralgia and purpuric skin rash was
      diagnosed with Henoch-Schonlein purpura (HSP) following an acute occurrence of
      his scrotal pain and swelling 17 days after the appearance of arthralgia.
      Immediate scrotal exploration was performed to confirm vasculitis of the left
      epididymis compatible with a scrotal manifestation of HSP. Postoperative course
      was uneventful. Twenty-five cases of HSP with acute scrotum reported in Japan,
      including this case, are calculated and discussed.

PMID- 15242377
TI  - Laparoscopic pyelolithotomy--a technique for the management of stones in the
      ectopic pelvic kidney.
AB  - We present our preliminary experience with the technique of laparoscopic
      pyelolithotomy for ectopic pelvic kidney calculi. This surgery has low morbidity
      and is ideally suited for the ectopic pelvic kidney with a laterally or
      anteriorly directed pelvis.

PMID- 15242379
TI  - The modulating effect of culture on the expression of dental anxiety in children:
      a literature review.
AB  - The experience of anxiety is a universal human phenomenon. Studies have shown a
      world-wide variation in the prevalence of dental anxiety with estimates ranging
      between 3% and 43%. The aetiology of dental anxiety is multifactorial, with
      factors acting in synergy to affect its expression. For children, age and gender
      play fundamental roles in its expression. However, these two factors are
      modulated by other variables such as culture which may influence the context in
      which anxiety is experienced, the interpretation of its meaning and responses to
      it. The modulating effect of culture in synergy with other variables may be one
      of the reasons why reports on dental anxiety have varied from region to region.
      This paper attempts to identify the interrelating roles of culture, age and
      gender, and how these relationships may affect variability in the expression and
      measurement of dental anxiety in children.

PMID- 15242380
TI  - Special Care Dentistry: attitudes of Specialists in Paediatric Dentistry
      practising in the UK to the creation of a new specialty.
AB  - OBJECTIVES: This study was designed to examine the attitudes of Specialists in
      Paediatric Dentistry (SPDs) practising in the UK towards the creation of a
      specialty of Special Care Dentistry (SCD). DESIGN: Data were collected by postal
      questionnaire. Sample and methods. Two hundred and eleven dentists whose names
      were entered on the General Dental Council's Specialist List in Paediatric
      Dentistry, and who were resident and practising in the UK, were asked to complete
      a questionnaire consisting of both open and closed questions. RESULTS:
      Questionnaires were returned by 167 (79.2%) of the eligible SPDs. One hundred and
      sixty respondents (95.8%) expressed an opinion in relation to the creation of a
      specialty of SCD. One hundred and forty-three respondents (85.6%) stated that
      they supported such a proposal. However, slightly fewer (n = 149) respondents
      were prepared to indicate what they considered to be the remit of the proposed
      specialty. Ninety-two respondents (55.1%) considered that it should be restricted
      to the provision of specialist care for adults with 'special needs'; the
      remaining 57 respondents felt that it should provide specialist care across the
      entire age spectrum. CONCLUSIONS: Among SPDs, there is overwhelming support for
      the creation of a specialty of SCD, the majority view being that this should be
      dedicated to the provision of specialist care for adults with 'special needs'.

PMID- 15242381
TI  - The effects of diet, breast-feeding and weaning on caries risk for pre-term and
      low birth weight children.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of dental
      disease in 3-4-year-old children born pre-term and low birth weight (PLBW) in
      East London, UK, to make comparisons with normal birth weight children (NBW), and
      to investigate the impact of dietary habits on the development of dental caries
      in primary teeth. DESIGN: This was a cross-sectional study. SUBJECTS AND METHODS:
      The subjects were 100 children (54 boys and 46 girls) with a mean age (+/- SD) of
      41.70 +/- 5.11 months. The children were resident within walking distance of the
      dental hospital and were invited to attend with their parents. Demographic data
      and information about feeding practices from infancy to the present were
      ascertained by structured questionnaire. Dental caries status was determined, and
      height, weight and head circumference were also measured. RESULTS: Sixty children
      had experienced dental caries with a mean (+/- SD) dmft of 2.98 +/- 3.93, 25 of
      whom had a dmft greater than 5. Normal birth weight children (3.00 +/- 4.18) and
      boys (3.55 +/- 4.48) had a significantly increased dmft over PLBW children (2.95
      +/- 3.35) and girls (2.29 +/- 3.04). The PLBW children were more likely to have
      used a bottle from birth and one in four children were still using a bottle at
      the time of the dental examination. The PLBW children were significantly more
      likely to eat sugar than NBW children, scoring 5.53 +/- 2.10 and 4.61 +/- 1.94,
      respectively. CONCLUSIONS: A clear relationship exists between poor diet and PLBW
      in a group of children resident in the East End of London. Targeted infant
      feeding programmes, education and support for families with regard to dental care
      is of importance to avoid an unnecessary amount of dental disease in young
      children.

PMID- 15242382
TI  - Fluoride content in bottled waters, juices and carbonated soft drinks in Mexico
      City, Mexico.
AB  - OBJECTIVE: The objective of this study was to analyse 283 samples of soft drinks
      available in the metropolitan market of Mexico City, Mexico: 105 juices, 101
      nectars, 57 carbonated drinks and 20 bottled waters. MATERIALS AND METHODS:
      Samples of the beverages were analysed using an Orion 720A potentiometer and an
      Orion 9609BN F ion-specific electrode. RESULTS: Fluoride concentration in the
      above-mentioned products ranged from 0.07 to 1.42 p.p.m. It was found that
      fluoride concentrations varied according to the brand, flavour and presentation
      of the product. The highest mean concentration of fluoride was found in the
      juices and cola drinks (0.67 +/- 0.38 and 0.49 +/- 0.41 p.p.m., respectively).
      The mean fluoride concentration for carbonated drinks was 0.43 +/- 0.36 p.p.m.
      Bottled waters had a fluoride concentration of 0.21 +/- 0.08 p.p.m. CONCLUSIONS:
      The findings suggest that fluoride ingested through bottled drinks represents an
      important part of the total fluoride ingested by the population. In view of the
      wide variation of fluoride concentration in the tested products, it is necessary
      to implement regulatory guidelines for controlling its concentration in order to
      prevent dental fluorosis.

PMID- 15242383
TI  - Fluid for thought: availability of drinks in primary and secondary schools in
      Cardiff, UK.
AB  - OBJECTIVE: While adequate hydration is undoubtedly essential for health, well
      being, performance and learning, it is important to recognize that drinks may
      also have significant detrimental effects on both general and dental health.
      Since, on weekdays, at least half of a child's recommended daily fluid intake
      must be imbibed at school, this study sought to examine the provision of drinks
      in that setting. SUBJECTS AND METHODS: A self-administered postal questionnaire
      study was sent to the head teachers of all 107 state primary and all 20 state
      secondary schools in Cardiff, South Wales, UK. RESULTS: A response rate of 81.9%
      was achieved. Children had access to fresh drinking water from at least one
      drinking fountain in 69 (66.4%) of the 104 schools who responded to the
      questionnaire. Milk was available in 69 (80.2%) of the 86 responding primary
      schools. Sixteen (88.9%) of the 18 responding secondary schools had drink vending
      machines selling a variety of drinks. CONCLUSIONS: While primary schools appear
      largely to restrict the availability of drinks to those conducive to the
      maintenance of good general and dental health, secondary schools appear to foster
      the use of vending machines. Guidelines should be developed on the use and
      content of vending machines in schools in order to both meet school objectives
      and promote healthy choices.

PMID- 15242384
TI  - Microleakage assessment of pit and fissure sealant with and without the use of
      pumice prophylaxis.
AB  - OBJECTIVES: This study evaluated the effect of pumice prophylaxis on the level of
      microleakage around and between the sealant and enamel. MATERIALS AND METHODS: A
      total of 32 freshly extracted sound upper first premolars, assigned as suitable
      for sealant application, were chosen and divided randomly into two groups: (1) a
      test group, without prophylaxis; and (2) a control group, with prophylaxis.
      Sealant was applied to all teeth using the same conventional technique, with
      prophylaxis being omitted in the test group. The sealed teeth were thermocycled
      (120 x 30 s, 5 and 55 degrees C cycles) and then immersed in 2% Basic Fuchsin
      solution for 72 h. Each tooth was sectioned and examined for dye penetration
      under a stereomicroscope (x 60 magnification). RESULTS: No dye penetration was
      seen in 19 (29.6%) of the teeth in the test group and 36 (56.2%) of the teeth in
      the control group. Dye had penetrated to the base of the fissure in 31 (48.4%) of
      the teeth in the test group and 23 (35.9%) of the teeth in the control group.
      Using a chi-square test for trend, the frequency of microleakage was
      significantly higher in the test group compared to the controls (P < 0.016).
      CONCLUSION: Prophylaxis has a role in improving sealant retention. Removing this
      step may cause an increase in microleakage.

PMID- 15242385
TI  - Nevoid basal cell carcinoma syndrome: a review of the literature and a report of
      a case.
AB  - The purpose of this paper is to report the development of multiple odontogenic
      keratocysts (OKCs) in a 15-year-old female with nevoid basal cell carcinoma
      syndrome (NBCCS) and review the literature pertinent to NBCCS. Although more than
      100 abnormalities have been reported in NBCCS, the development of OKCs is one of
      its principle features. In view of this, the patient was subjected to further
      medical, dermatological and radiographic investigation. Multiple basal cell naevi
      and skeletal anomalies associated with NBCCS were found. Because of the autosomal
      dominant inheritance of this syndrome, the patient's family was then
      investigated. The patient's father was found to have multiple OKCs. The report
      highlights the need for vigilance in considering the diagnosis of NBCCS in all
      cases of OKCs, particularly those affecting young patients.

PMID- 15242386
TI  - Papillon-Lefevre syndrome: a report of two cases.
AB  - Papillon-Lefevre syndrome is a rare disease characterized by skin lesions caused
      by palmar-plantar hyperkeratosis, and severe periodontal destruction involving
      both the primary and permanent dentitions. It is transmitted as an autosomal
      recessive condition and consanguinity of parents is evident in about one-third of
      cases. This paper describes two preschool children who presented at the
      Paediatric Dentistry Department, Sheffield, UK, with progressively loosening
      teeth and discomfort during eating. The medical history revealed scaling on the
      hands and feet, which had been medically diagnosed as eczema. Papillon-Lefevre
      syndrome was diagnosed in both cases.

PMID- 15242387
TI  - Talon cusp associated with other dental anomalies: a case report.
AB  - Talon cusp is an uncommon dental anomaly referring to an accessory cusp
      projecting from the cingulum area, or cemento-enamel junction of maxillary or
      mandibular anterior teeth, in both the primary and permanent dentition. This
      paper reports a rare case of talon cusp affecting the mandibular right central
      incisor and maxillary right lateral incisor, together with other dental
      abnormalities, viz. an inverted impacted migrating mandibular right second
      premolar; complete agenesis of the maxillary and mandibular third molars, the
      maxillary right second permanent molar, and the mandibular left permanent central
      incisor; severe crowding; deep bite; hypoplastic teeth; bilateral reverse cross
      bite in the premolar region; and a retrognathic mandible. The presence of this
      number of dental anomalies in a single patient is rare.

PMID- 15242388
TI  - Defective enamel ultrastructure in diabetic rodents.
AB  - We investigated six different types of diabetic rodents. Four expressed a genetic
      obesity resulting in diabetes. One developed diabetes induced by a diet-dependent
      obesity, and one with genetic diabetes received anti-diabetic medication. The
      tooth samples were examined under a scanning electron microscope and with an
      energy dispersive microanalysis (EDX). The electron micrographs showed severe,
      varying degrees of damage within the six different diabetic animal types, such as
      irregular crystallite deposition and prism perforations in genetically obese
      animals compared to less-disordered prism structures in diet-dependent obesity.
      Anti-diabetic medication resulted in normal enamel ultrastructure. The EDX
      analysis revealed a reduction in the amount of calcium and phosphorus in all
      regions affected by diabetes. Based on these animal studies, we suggest that both
      juvenile diabetes type I (in infants) and adult diabetes type II (in pregnant
      mothers, affecting the developing foetus) may affect the normal development of
      teeth in humans.

PMID- 15242391
TI  - V(D)J recombination.

PMID- 15242392
TI  - The phylogenetic origins of the antigen-binding receptors and somatic
      diversification mechanisms.
AB  - The adaptive immune system arose in ancestors of the jawed vertebrates
      approximately 500 million years ago. Homologs of immunoglobulins (Igs), T-cell
      antigen receptors (TCRs), major histocompatibility complex I (MHC I) and MHC II,
      and the recombination-activating genes (RAGs) have been identified in all extant
      classes of jawed vertebrates; however, no definitive homolog of any of these
      genes has been identified in jawless vertebrates or invertebrates. RAG-mediated
      recombination and associated junctional diversification of both Ig and TCR genes
      occurs in all jawed vertebrates. In the case of Igs, somatic variation is
      expanded further through class switching, gene conversion, and somatic
      hypermutation. Although the identity of the 'primordial' receptor that was
      interrupted by the recombination mechanism in jawed vertebrates may never be
      established, many different families of genes that exhibit predicted
      characteristics of such a receptor have been described both within and outside
      the jawed vertebrates. Recent data from various model systems point toward a
      continuum of immune receptor diversity, encompassing many different families of
      recognition molecules whose functions are integrated in an organism's response to
      pathogenic invasion. Various approaches, including both genomic and protein
      functional analyses, currently are being applied in jawless vertebrates,
      protochordates, and other invertebrate deuterostome systems and may yield
      definitive evidence regarding the presence or absence of adaptive immune homologs
      in species lacking adaptive immune systems. Such studies have the potential for
      uncovering previously unknown mechanisms of generating receptor diversity.

PMID- 15242393
TI  - In vitro and in vivo studies on the generation of the primary T-cell receptor
      repertoire.
AB  - The primary T-cell receptor repertoire is generated by somatic rearrangement of
      discontinuous gene segments. The shape of the combinatorial repertoire is
      stereotypical and, in part, evolutionarily conserved among mammals. Rearrangement
      is initiated by specific interactions between the recombinase and the
      recombination signals (RSs) that flank the gene segments. Conserved sequence
      variations in the RS, which modulate its interactions with the recombinase,
      appear to be a major factor in shaping the primary repertoire. In vitro,
      biochemical studies have revealed distinct steps in these complex recombinase-RS
      interactions that may determine the final frequency of gene segment
      rearrangement. These studies offer a plausible model to explain gene segment
      selection, but new, more physiological approaches will have to be developed to
      verify and refine the mechanism by which the recombinase targets the RS in its
      endogenous chromosomal context in vivo.

PMID- 15242394
TI  - Regulation of T-cell receptor beta-chain gene assembly by recombination signals:
      the beyond 12/23 restriction.
AB  - Assembly of antigen receptor genes is regulated in several important contexts
      during lymphocyte development. This regulation occurs through modulation of gene
      segment accessibility to the V(D)J recombinase and/or at the level of the
      recombination reaction due, in part, to constraints imposed by recombination
      signal (RS) sequences. RSs are composed of conserved heptamer and nonamer
      sequences that flank relatively non-conserved spacer sequences of either 12 or 23
      base pairs. Recombination occurs only between RSs of dissimilar spacer lengths, a
      restriction known as the 12/23 rule. Recently, we have shown that RSs can impose
      significant constraints on antigen receptor gene assembly beyond enforcing the
      12/23 rule. This restriction, termed B12/23, was revealed by analysis of T-cell
      receptor beta (TCRbeta) locus rearrangements, where Dbeta 12RSs and not Jbeta
      12RSs are capable of efficiently targeting Vbeta 23RSs' rearrangement. The B12/23
      restriction occurs at or prior to the DNA-cleavage step of the V(D)J
      recombination reaction, relies on features of the Dbeta 12RSs and Vbeta 23RSs,
      and is not absolutely dependent on lymphoid-specific factors other than the
      recombinase-activating gene-1 (RAG-1) and RAG-2 proteins. By preserving Dbeta
      gene segment utilization, the B12/23 restriction is required, at a minimum, for
      the generation of a diverse repertoire of TCRbeta chains.

PMID- 15242395
TI  - Many levels of control of V gene rearrangement frequency.
AB  - V, D, and J gene segments rearrange at very different frequencies. As with most
      biological systems, there are multiple levels of control of V gene recombination
      frequency, and here we review some of the work from our laboratory that addresses
      these various control mechanisms. One of the important factors that affect non
      random V gene rearrangement frequency is the natural heterogeneity in
      recombination signal sequences (RSSs). Not only does variation in the heptamer
      and nonamer affect rearrangement, but variation in the spacer can also
      dramatically affect recombination. However, there are clearly other factors which
      control V gene rearrangement, as revealed by the fact that genes with identical
      RSSs can rearrange at different frequencies in vivo. Some of these other
      influences most likely affect the earliest stages of control--the change from an
      inaccessible state to an accessible state. Transcription factors can play a role
      in inducing these changes. Rearrangement of many VkappaI genes can be induced in
      a non-lymphoid cell line after ectopic expression of E2A, while neighboring
      VkappaII and VkappaIII genes do not rearrange, demonstrating that at least one
      level of control of induction of accessibility occurs at the level of the
      individual gene. Also, changes in chromatin structure can affect accessibility
      and might influence individual V gene rearrangement frequency.

PMID- 15242396
TI  - Computational tools for understanding sequence variability in recombination
      signals.
AB  - The recombination signals (RSs) that guide V(D)J rearrangement are remarkably
      diverse. In mice, fewer than 16% of RSs carry consensus heptamers and nonamers
      and none also contain a consensus spacer sequence. It is increasingly clear that
      this variability regulates recombination: genetic variability in RSs may help
      enforce allelic exclusion, determine the general nature of antigen receptor
      repertoires, and mitigate autoreactivity in B lymphocytes. The great diversity of
      RSs has largely precluded, however, empiric determinations of how RS sequence
      affects recombination. For example, 4(39) unique 23-RSs are possible or
      approximately 3 x 10(23) sequences; some 7 x 10(13) unique 23-RSs can be produced
      just by changes in the spacer. In contrast, the recombination activities of only
      100 or so RSs have been measured, and it is unlikely that the activities of even
      a tiny fraction of extant RSs can be determined. We have addressed the problem of
      how sequence determines the efficiency of RS templates by generating
      computational models that describe the correlation structure of mouse RSs. These
      models successfully predict RS activity and identify functional, cryptic RSs
      (cRSs). These models permit studies to identify RSs and cRSs for empiric study
      and constitute a tool useful for understanding RS structure and function.

PMID- 15242397
TI  - Putting the pieces together: identification and characterization of structural
      domains in the V(D)J recombination protein RAG1.
AB  - V(D)J recombination generates functional immunoglobulin and T-cell receptor genes
      in developing lymphocytes. The recombination-activating gene 1 (RAG1) and RAG2
      proteins catalyze site-specific DNA cleavage in this recombination process.
      Biochemical studies have identified catalytically active regions of each protein,
      referred to as the core regions. Here, we review our progress in the
      identification and characterization, in biophysical and biochemical terms, of
      topologically independent domains within both the non-core and core regions of
      RAG1. Previous characterizations of a structural domain identified in the non
      core region of RAG1 from residues 265-380, referred to as the zinc-binding
      dimerization domain, are discussed. This domain contains two zinc-binding motifs,
      a RING finger and a C2H2 zinc finger. Core RAG1 also consists of multiple
      domains, each of which functions individually in one or more of the essential
      macromolecular interactions formed by the intact core protein. Two structural
      domains referred to as the central and the C-terminal domains that include
      residues 528-760 and 761-979 of RAG1, respectively, have been identified. The
      interactions of the central and C-terminal domains in core RAG1 with the
      recombination signal sequence (RSS) have contributed additional insight to a
      developing model for the RAG1-RSS complex.

PMID- 15242398
TI  - Recombination-activating gene proteins: more regulation, please.
AB  - Developing B and T cells assemble gene segments in order to create the variable
      regions of immunoglobulin and T-cell receptors required by our adaptive immune
      response. The chemistry of this recombination pathway requires a specific
      nuclease and a more general repair pathway for double-strand breaks. A complex of
      the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the
      nuclease activity. In fact, RAG1 and RAG2 probably coordinate many steps
      involving the coding and signaling DNA sequences. Studies using deletion and
      truncation mutants of the RAG proteins demonstrate that each of these contain a
      functional core region, representing about two-thirds of the polypeptides. While
      the core regions are sufficient to catalyze recombination in test systems, the
      full-length proteins seem to show more complicated behaviors in vivo. A plausible
      explanation is that regions outside the core help in the proper regulation of
      recombination. The non-core region of RAG1 has been found to contain a ubiquitin
      ligase. Regulatory functions may contribute to autoregulation of the proteins
      involved, fidelity of the reaction, protection of the cell from translocations,
      coordination of recombination with the cell cycle, and possibly modification of
      the chromatin structure of target DNA.

PMID- 15242399
TI  - The bounty of RAGs: recombination signal complexes and reaction outcomes.
AB  - V(D)J recombination is a form of site-specific DNA rearrangement through which
      antigen receptor genes are assembled. This process involves the breakage and
      reunion of DNA mediated by two lymphoid cell-specific proteins, recombination
      activating genes RAG-1 and RAG-2, and ubiquitously expressed architectural DNA
      binding proteins and DNA-repair factors. Here I review the progress toward
      understanding the composition, assembly, organization, and activity of the
      protein-DNA complexes that support the initiation of V(D)J recombination, as well
      as the molecular basis for the sequence-specific recognition of recombination
      signal sequences (RSSs) that are the targets of the RAG proteins. Parallels are
      drawn between V(D)J recombination and Tn5/Tn10 transposition with respect to the
      reactions, the proteins, and the protein-DNA complexes involved in these
      processes. I also consider the relative roles of the different sequence elements
      within the RSS in recognition, cleavage, and post-cleavage events. Finally, I
      discuss alternative DNA transactions mediated by the V(D)J recombinase, the
      protein-DNA complexes that support them, and factors and forces that control
      them.

PMID- 15242400
TI  - The role of the non-homologous end-joining pathway in lymphocyte development.
AB  - One of the most toxic insults a cell can incur is a disruption of its linear DNA
      in the form of a double-strand break (DSB). Left unrepaired, or repaired
      improperly, these lesions can result in cell death or neoplastic transformation.
      Despite these dangers, lymphoid cells purposely introduce DSBs into their genome
      to maximize the diversity and effector functions of their antigen receptor genes.
      While the generation of breaks requires distinct lymphoid-specific factors, their
      resolution requires various ubiquitously expressed DNA-repair proteins, known
      collectively as the non-homologous end-joining pathway. In this review, we
      discuss the factors that constitute this pathway as well as the evidence of their
      involvement in two lymphoid-specific DNA recombination events.

PMID- 15242401
TI  - The DNA-dependent protein kinase: the director at the end.
AB  - Efficient repair of DNA double-strand breaks is essential for the maintenance of
      chromosomal integrity. In higher eukaryotes, non-homologous end-joining (NHEJ)
      DNA is the primary pathway that repairs these breaks. NHEJ also functions in
      developing lymphocytes to repair strand breaks that occur during V(D)J
      recombination, the site-specific recombination process that provides for the
      assembly of functional antigen-receptor genes. If V(D)J recombination is
      impaired, B- and T-lymphocyte development is blocked resulting in severe combined
      immunodeficiency disease. In the last decade, an intensive research effort has
      focused on NHEJ resulting in a reasonable understanding of how double-strand
      breaks are resolved. Six distinct gene products have been identified that
      function in this pathway (Ku70, Ku86, XRCC4, DNA ligase IV, Artemis, and DNA
      PKcs). Three of these comprise one complex, the DNA-dependent protein kinase (DNA
      PK). This protein complex is central during NHEJ, because DNA-PK initially
      recognizes and binds to the damaged DNA and then targets the other repair
      activities to the site of DNA damage. In this review, we discuss recent
      developments that have provided insight into how DNA-PK functions, once bound to
      DNA ends.

PMID- 15242402
TI  - Artemis sheds new light on V(D)J recombination.
AB  - V(D)J recombination represents one of the three mechanisms that contribute to the
      diversity of the immune repertoire of B lymphocytes and T lymphocytes. It also
      constitutes a major checkpoint during the development of the immune system.
      Indeed, any V(D)J recombination deficiency leads to a block of B-cell and T-cell
      maturation in humans and animal models, leading to severe combined
      immunodeficiency (T-B-SCID). Nine factors have been identified so far to
      participate in V(D)J recombination. The discovery of Artemis, mutated in a subset
      of T-B-SCID, provided some new information regarding one of the missing V(D)J
      recombinase activities: hairpin opening at coding ends prior to DNA repair of the
      recombination activating genes 1/2-generated DNA double-strand break. New
      conditions of immune deficiency in humans are now under investigations and should
      lead to the identification of additional V(D)J recombination/DNA repair factors.

PMID- 15242403
TI  - Sibling rivalry: competition between Pol X family members in V(D)J recombination
      and general double strand break repair.
AB  - The nonhomologous end-joining pathway is a major means for repairing double
      strand breaks (DSBs) in all mitotic cell types. This repair pathway is also the
      only efficient means for resolving DSB intermediates in V(D)J recombination, a
      lymphocyte-specific genome rearrangement required for assembly of antigen
      receptors. A role for polymerases in end-joining has been well established. They
      are a major factor in determining the character of repair junctions but, in
      contrast to 'core' end-joining factors, typically appear to have a subtle impact
      on the efficiency of end-joining. Recent work implicates several members of the
      Pol X family in end-joining and suggests surprising complexity in the control of
      how these different polymerases are employed in this pathway.

PMID- 15242404
TI  - How to keep V(D)J recombination under control.
AB  - Breaking apart chromosomes is not a matter to be taken lightly. The possible
      negative outcomes are obvious: loss of information, unstable chromosomes,
      chromosomal translocations, tumorigenesis, or cell death. Utilizing DNA
      rearrangement to generate the desired diversity in the antigen receptor loci is a
      risky business, and it must be carefully controlled. In general, the regulation
      is so precise that the negative consequences are minimal or not apparent. They
      are visible only when the process of V(D)J recombination goes awry, as for
      example in some chromosomal translocations associated with lymphoid tumors.
      Regulation is imposed not only to prevent the generation of random breaks in the
      DNA, but also to direct rearrangement to the appropriate locus or subregion of a
      locus in the appropriate cell at the appropriate time. Antigen receptor
      rearrangement is regulated essentially at four different levels: expression of
      the RAG1/2 recombinase, intrinsic biochemical properties of the recombinase and
      the cleavage reaction, the post-cleavage /DNA repair stage of the process, and
      accessibility of the substrate to the recombinase. Within each of these broad
      categories, multiple mechanisms are used to achieve the desired aims. The major
      focus of this review is on accessibility control and the role of chromatin and
      nuclear architecture in achieving this regulation, although other issues are
      touched upon.

PMID- 15242405
TI  - Regulation of immunoglobulin heavy-chain gene rearrangements.
AB  - Regulated assembly of antigen receptor gene segments to produce functional genes
      is a hallmark of B- and T-lymphocyte development. The immunoglobulin heavy-chain
      (IgH) and T-cell receptor beta-chain genes rearrange first in B and T lineages,
      respectively. Both loci require two recombination events to assemble functional
      genes; D-to-J recombination occurs first followed by V-to-DJ recombination.
      Despite similarities in overall rearrangement patterns, each locus has unique
      regulatory features. Here, we review the characteristics of IgH gene
      rearrangements such as developmental timing, deletion versus inversion, DH gene
      segment utilization, ordered recombination of VH gene segments, and feedback
      inhibition of rearrangement in pre-B cells. We summarize chromatin structural
      features of the locus before and during recombination and, wherever possible,
      incorporate these into working hypotheses for understanding regulation of IgH
      gene recombination. The picture emerges that the IgH locus is activated in
      discrete, independently regulated domains. A domain encompassing DH and JH gene
      segments is activated first, within which recombination is initiated. VH genes
      are activated subsequently and, in part, by interleukin-7. These observations
      lead to a model for feedback inhibition of IgH rearrangements.

PMID- 15242406
TI  - Monoallelic gene expression: a repertoire of recurrent themes.
AB  - The development of mature B and T cells in the lymphoid system involves a series
      of molecular decisions that culminate in the expression of a single antigen
      receptor on the cell surface, a phenomenon termed allelic exclusion. While
      feedback inhibition of the recombinase-activation gene proteins evidently plays
      an important role in the maintenance of allelic exclusion, the initial
      restriction of rearrangement to only one allele in each cell seems to be achieved
      through monoallelic epigenetic changes. Epigenetic mechanisms involved in the
      establishment of allelic exclusion also play a central role in other types of
      monoallelic expression, including X-chromosome inactivation in female cells, and
      parental imprinting. In all three systems, the inequality of the two alleles
      seems to be achieved mainly by differential DNA methylation, asynchronous DNA
      replication, differential chromatin modifications, unequal nuclear localization,
      and non-coding RNA. In this review, we discuss the unifying features among these
      monoallelically expressed systems and the unique characteristics displayed by
      each of them.

PMID- 15242407
TI  - Regulation of activation and recombination of the murine Igkappa locus.
AB  - The murine immunoglobulin (Ig) kappa locus has been intensively studied in an
      attempt to understand its developmentally regulated activation for both
      transcription and V(D)J recombination. A variety of signaling proteins, cis
      acting DNA elements, and trans-acting DNA-binding proteins have been discovered
      and shown to be involved in the regulated changes in chromatin structure, which
      are associated with recombinase accessibility. In addition, key roles have been
      suggested for DNA methylation and replication in kappa-locus expression and
      rearrangement. This review summarizes data in this area and considers what
      studies of the murine kappa locus have revealed about the lineage specificity,
      order, and allelic exclusion of lymphoid V(D)J recombination.

PMID- 15242408
TI  - Enforcing order within a complex locus: current perspectives on the control of
      V(D)J recombination at the murine T-cell receptor alpha/delta locus.
AB  - V(D)J recombination proceeds according to defined developmental programs at T
      cell receptor (TCR) and immunoglobulin loci as a function of cell lineage and
      stage of differentiation. Although the molecular details are still lacking, such
      regulation is thought to occur at the level of accessibility of chromosomal
      recombination signal sequences to the recombinase. The unique and complex
      organization of the TCRalpha/delta locus poses intriguing regulatory challenges
      in this regard: embedded TCRalpha and TCRdelta gene segments rearrange at
      distinct stages of thymocyte development, there is a highly regulated progression
      of primary followed by secondary rearrangements involving Jalpha segments, and
      there are important developmental constraints on V gene segment usage. The locus
      therefore provides a fascinating laboratory in which to explore the basic
      mechanisms underlying developmental control. We provide here a current view of
      cis-acting mechanisms that enforce the TCRalpha/delta locus developmental
      program, and we emphasize the unresolved issues that command the attention of our
      and other laboratories.

PMID- 15242409
TI  - The taming of a transposon: V(D)J recombination and the immune system.
AB  - The genes that encode immunoglobulins and T-cell receptors must be assembled from
      the multiple variable (V), joining (J), and sometimes diversity (D) gene segments
      present in the germline loci. This process of V(D)J recombination is the major
      source of the immense diversity of the immune repertoire of jawed vertebrates.
      The recombinase that initiates the process, recombination-activating genes 1
      (RAG1) and RAG2, belongs to a large family that includes transposases and
      retroviral integrases. RAG1/2 cleaves the DNA adjacent to the gene segments to be
      recombined, and the segments are then joined together by DNA repair factors. A
      decade of biochemical research on RAG1/2 has revealed many similarities to
      transposition, culminating with the observation that RAG1/2 can carry out
      transpositional strand transfer. Here, we discuss the parallels between V(D)J
      recombination and transposition, focusing specifically on the assembly of the
      recombination nucleoprotein complex, the mechanism of cleavage, the disassembly
      of post-cleavage complexes, and aberrant reactions carried out by the recombinase
      that do not result in successful locus rearrangement and may be deleterious to
      the organism. This work highlights the considerable diversity of transposition
      systems and their relation to V(D)J recombination.

PMID- 15242410
TI  - V(D)J recombination: how to tame a transposase.
AB  - Since the discovery that the recombination-activating gene (RAG) proteins were
      capable of transposition in vitro, investigators have been trying to uncover
      instances of transposition in vivo and understand how this transposase has been
      harnessed to do useful work while being inhibited from causing deleterious
      chromosome rearrangements. How to preserve the capacity of the recombinase to
      promote a certain class of rearrangements while curtailing its ability to
      catalyze others is an interesting problem. In this review, we examine the
      progress that has been made toward understanding the regulatory mechanisms that
      prohibit transposition in order to formulate a model that takes into account the
      diverse observations that have been made over the last 15 years. First, we touch
      on the striking mechanistic similarities between transposition and V(D)J
      recombination and review evidence suggesting that the RAG proteins may be members
      of the retroviral integrase superfamily. We then dispense with an old theory that
      certain standard products of V(D)J recombination called signal joints protect
      against deleterious transposition events. Finally, we discuss the evidence that
      target capture could serve a regulatory role and close with an analysis of
      hairpins as preferred targets for RAG-mediated transposition. These novel
      strategies for harnessing the RAG transposase not only shed light on V(D)J
      recombination but also may provide insight into the regulation of other
      transposases.

PMID- 15242411
TI  - New concepts in the regulation of an ancient reaction: transposition by
      RAG1/RAG2.
AB  - The lymphoid-specific factors, recombination-activating gene 1 (RAG1) and RAG2,
      initiate V(D)J recombination by introducing DNA double-stand breaks at specific
      sites in the genome. In addition to this critical endonuclease activity, the RAG
      proteins catalyze other chemical reactions that can affect the outcome of V(D)J
      recombination, one of which is transposition. While the transposition activity of
      the RAG proteins is thought to have been critical for the evolution of modern
      antigen-receptor loci, it has also been proposed to contribute to chromosomal
      translocations and lymphoid malignancy. A major challenge has been to determine
      how the transposition activity of the RAG proteins is regulated in vivo. Although
      a variety of mechanisms have been suggested by recent studies, a clear resolution
      of this issue remains elusive.

PMID- 15242413
TI  - Transient global amnesia -- not always a benign process.
AB  - OBJECTIVES: Transient global amnesia (TGA) is an episodic dysfunction of
      declarative memory, which is assumed to be a benign disorder. Brain perfusion
      single photon emission computed tomography (SPECT) was shown to be abnormal
      during the acute stage and to become normal with normalization of memory
      function. No data are known about the brain perfusion pattern among these
      patients with recurrent TGA. MATERIAL AND METHODS: Sixteen patients with TGA were
      studied with an initial brain imaging during the acute stages of their attack,
      and a second imaging was performed after 3 months. In the event of a patients
      having a second abnormal brain perfusion HMPAO SPECT, a third imaging was
      performed after 1 year. RESULTS: Hypofusion perfusion was demonstrated in all
      cases during the acute stage. In all patients who had a first TGA, a normal SPECT
      was demonstrated after 3 months. In three patients with recurrent TGA, the brain
      perfusion remained abnormal after 3 months and after 1 year. CONCLUSIONS: A
      normal perfusion in TGA after 3 months can be expected in a patient with a first
      attack. In patients with recurrent TGA attacks, a persistent focal hypoperfusion
      can be expected. This subgroup of patients may demonstrate a non-benign type of
      TGA, eventually due to a different etiology of event.

PMID- 15242414
TI  - The effects of endurance training in persons with a hereditary myosin myopathy.
AB  - OBJECTIVE: To evaluate muscle performance and its consequences in eight
      individuals with a hereditary myopathy and the effects of an 8-week endurance
      training program. MATERIAL AND METHODS: Handgrip, muscle strength and endurance
      and oxygen consumption by breath-by-breath analysis during a stepless bicycle
      ergonometer test were evaluated. Walking, balance test and activities of daily
      living (ADL) were assessed, and a questionnaire for activity level and perceived
      symptoms was used. The design was a before-after trial in comparison with data
      from a control population, bicycling at 70% of maximal workload, 30 min/day, 5
      days/week for 8 weeks. RESULTS: The subjects were weaker than age-matched
      controls. After training, the peak watt increased by almost 20% (P < 0.05).
      Muscle strength (flexion/extension) and isometric endurance (40% of maximum at 60
      degrees ) did not change significantly. The average self-selected walking speed
      increased significantly (P < 0.05) from 1.25 to 1.45 m/s. Compliance was
      excellent and no serious adverse events occurred. CONCLUSION: Endurance training
      seems to function for this myopathy.

PMID- 15242415
TI  - Muscle magnetic resonance imaging shows distinct diagnostic patterns in Welander
      and tibial muscular dystrophy.
AB  - OBJECTIVES: This is a report on a retrospective muscle magnetic resonance imaging
      (MRI) study on 11 patients affected by Welander distal myopathy (WDM) and 22
      patients with tibial muscular dystrophy (TMD) carried out in order to define the
      pattern and characteristics of muscle involvement. RESULTS: WDM patients showed
      involvement of gastrocnemius, soleus, tibial anterior (TA) and extensor digitorum
      longus (EDL), as well as hamstrings and hip adductor muscles. TMD patients showed
      involvement of the TA and EDL muscles, and in some patients also hamstring and
      posterior compartment muscles of the legs. Some patients showed asymmetry of
      muscle involvement. CONCLUSION: We conclude that muscle MRI examination proved to
      be very useful in the determination of the exact pattern of muscle involvement in
      WDM and TMD. Clinical testing using the Medical Research Council scale is not
      sensitive enough to establish the pattern of muscle involvement in focal muscle
      diseases.

PMID- 15242416
TI  - High mortality of subjects with endemic ataxic polyneuropathy in Nigeria.
AB  - BACKGROUND: Endemic ataxic polyneuropathy, a neurological syndrome that was
      thought to be benign, has been shown to persist in some communities in south
      western Nigeria, where it was first described in the 1950s. OBJECTIVES: This
      study was conducted to compare mortality of cases and controls, and to determine
      if mortality is related to exposure to cyanide from cassava foods. MATERIAL AND
      METHODS: Cases of endemic ataxic polyneuropathy and two groups of controls, one
      group living in an endemic community and the other group living in a non-endemic
      community, were followed for 25 months. The outcome was death from medical
      causes. RESULTS: A total of 5970 subjects, 204 cases and 5766 controls - 4000
      controls in the endemic community and 1766 controls in the non-endemic community,
      were followed. A total of 153 subjects died, 24 cases, 115 controls in the
      endemic community, and 14 controls in the non-endemic community. Relative risks
      of death (95% CI), adjusted for age and gender, were 4.5 (2.3-8.9) for cases (P <
      0.0001), but 2.6 (1.5-4.6) for controls living in the endemic community (P =
      0.001). CONCLUSION: This study shows that endemic ataxic polyneuropathy decreases
      survival. The finding of lower risk of death in the community with higher
      exposure to cyanide from cassava foods indicates that mortality of endemic ataxic
      polyneuropathy is not associated with exposure to cyanide from cassava foods.

PMID- 15242417
TI  - Incidence and clinical features of acute inflammatory polyradiculoneuropathy in
      Lombardy, Italy, 1996.
AB  - OBJECTIVE: To assess the annual incidence of typical Guillain-Barre syndrome
      (GBS) and its main variants (atypical GBS) in a well-defined population from a
      large area. MATERIAL AND METHODS: A population-based prospective survey of GBS
      was undertaken during the calendar year 1996 in Lombardy, Italy (population
      8,891,652). Typical and atypical GBS was diagnosed using the National Institutes
      of Neurological and Communicative Disorders and Stroke (NINCDS) and Ropper
      criteria. Eligible cases were hospital inpatients traced through a regional
      registry, the hospital discharge diagnoses, and an ongoing case-control study.
      Diagnostic and demographic findings were collected for each case. Complete
      clinical and laboratory features were available for 80% of cases. RESULTS: A
      total of 138 patients (males 74; females 64) aged 2-91 years fulfilled the
      diagnostic criteria for typical GBS (128) or atypical GBS (10). GBS variants
      included Miller-Fisher syndrome (four cases), cranial polyneuritis (three cases),
      pure motor GBS (two cases), and sensory loss with areflexia (one case). The crude
      annual incidence of GBS was 1.55 per 100,000 (typical GBS 1.43; atypical GBS
      0.11; male 1.67; female 1.43; age <35 years, 0.79; 35-54 years, 1.33; 55-74
      years, 3.22; 75+ years, 4.67). The overall rate was 1.58 when age- and sex
      adjusted to the 1996 Italian population. Previous infections were reported for
      37% of patients. The electrophysiological findings indicated demyelination in
      51%, primary axonopathy in 14%, and mixed myelin and axon involvement in 27%.
      CONCLUSIONS: The incidence of typical GBS is comparable with that in other
      reports using the NINCDS diagnostic criteria. Atypical GBS accounts for a limited
      number of cases.

PMID- 15242418
TI  - Long-term outcome of cerebral infarction in young adults.
AB  - OBJECTIVES: We analysed the long-term outcome of 232 young adults aged 15-49
      years with first-ever cerebral infarction in 1988-1997 in western Norway.
      MATERIAL AND METHODS: Mortality, recurrence, epilepsy, functional state as
      evaluated by modified Rankin scale (mRS), and employment were analysed at follow
      up (mean time 5.7 years). RESULTS: Twenty-three (9.9%) patients had died.
      Recurrence occurred in 9.9%, and post-stroke seizures developed in 10.5%.
      Recurrence was associated with diabetes mellitus (P = 0.005). Favourable
      functional outcome (mRS = 2) was found in 77.9%. The functional outcome was
      better in posterior than anterior circulation infarctions (P = 0.011).
      Unfavourable functional outcome (mRS > 2) was associated with diabetes mellitus
      (P = 0.001) and severity of neurological deficits on admission for the index
      stroke (P < 0.001). Only 58.3% were employed at follow-up. CONCLUSION: This
      population-based study shows that, although the majority had favourable
      functional outcome, cerebral infarction had major long-term impact on young
      adults as evaluated by mortality, recurrence and employment status.

PMID- 15242419
TI  - The antibodies against Bordetella pertussis in sera of patients with Parkinson's
      disease and other non-neurological diseases.
AB  - OBJECTIVES: It has been reported that the prevalance of parkinsonism might be
      associated with exposure to whooping cough. METHODS: Examination of levels of
      antibodies against Bordetella pertussis in serum using enzyme-linked
      immunosorbent assay (ELISA) tests [presence of IgG antibodies against filamentous
      hemagglutinin and pertussis toxin (PT)] were performed in 81 persons (including
      45 patients with controls) (age-matched groups). RESULTS: Positive results were
      found in patients with Parkinson's disease (PD), patients with other non
      inflammatory diseases, and controls (about 40-45% in each group). A detailed
      examination of separate responses (IgG and IgA antibodies against PT, and a whole
      cell immune response) and of the serum level of immunoglobulins IgG, IgA and IgM
      was also performed. CONCLUSION: Our results demonstrate numerous cases of
      whooping cough serum antibodies among the adult population (also among PD
      patients). The results of our research, i.e. a common occurrence of Bordetella
      pertussis infection do not provide evidence of relationship between PD and the
      above-mentioned infection.

PMID- 15242420
TI  - Mortality in Parkinson's disease and its association with dementia and
      depression.
AB  - OBJECTIVE: To compare the mortality rate in Parkinson's disease (PD) with a
      control group without PD, and to assess the relationship between mortality and
      features of PD. MATERIAL AND METHODS: Ninety PD patients and 50 controls,
      mortality ascertained at 11 years follow-up. RESULTS: The hazard ratio (HR) for
      mortality in PD patients compared with controls was 1.64 (95% CI: 1.21-2.23).
      Multivariate analysis showed age, dementia and depression were independent
      predictors of mortality but age at onset of PD and severity of neurological
      symptoms were not. The HR for age was 1.09 (95% CI: 1.05-1.13), for dementia 1.94
      (95% CI: 1.26-2.99), and for depression 2.66 (95% CI: 1.59-4.44). CONCLUSION:
      Mortality in PD is increased compared with controls. Psychological variables are
      important predictors of mortality in PD.

PMID- 15242421
TI  - Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia
      patients.
AB  - OBJECTIVES: To investigate a possible implication of inflammatory processes in
      the development of dementia in cerebrovascular disease. PATIENTS AND METHODS: We
      examined the levels of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of
      patients with Alzheimer's disease (AD) (n = 26), ischemic cerebrovascular disease
      without dementia (CVD) (n = 11), vascular dementia (VD) (n = 11), and other
      neurological disorders (n = 21) using sensitive enzyme-linked immunosorbent
      assay. RESULTS: The CSF concentrations of IL-6 were significantly elevated in
      patients with VD compared with those of patients with AD or CVD. CONCLUSION: The
      CSF IL-6 levels are increased in patients with VD, suggesting that inflammatory
      mechanisms may be involved in the development of cognitive decline in some
      patients with cerebrovascular disease. CSF IL-6 may be a biological marker for
      dementia in cerebrovascular disease.

PMID- 15242422
TI  - Midbrain hypometabolism as early diagnostic sign for progressive supranuclear
      palsy.
AB  - OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early
      phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2
      deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis
      of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using
      SPM99 and analysis of covariance to eliminate the effect of aging, the
      differences between PSP and normals were displayed as a statistical map. In the
      PSP, we also investigated the correlation with duration and with the subscores of
      Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of
      midbrain was significantly lower in PSP than in normals. However, correlation was
      not found between the metabolism of midbrain and clinical deterioration.
      CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of
      midbrain in PSP, which is independent of the clinical deterioration. The
      hypometabolism of midbrain is one of the most promising sign for early diagnosis
      of PSP.

PMID- 15242423
TI  - Glucocorticoid regulation of the inflammatory response to injury.
AB  - During the first half of the 20th century, physiologists were interested in the
      adrenal glands primarily because adrenalectomized animals failed to survive even
      mild degrees of systemic stress. It eventually became clear that hormones
      secreted by the adrenal cortex were critical for survival and, in this context,
      adrenal cortical hormones were widely considered to support or stimulate
      important responses to stress or injury. With the purification and manufacture of
      adrenal cortical hormones in the 1930s and 1940s, clinicians suddenly discovered
      the potent anti-inflammatory actions of glucocorticoids (GCs). This dramatic, and
      unexpected, discovery has dominated clinical and laboratory research into GC
      actions throughout the second half of the 20th century. More recent research is
      again reporting GC-induced stimulatory effects on a variety of inflammatory
      response components. These effects are usually observed at low GC concentrations,
      close to concentrations that are observed in vivo during basal, unstimulated
      states. For example, GC-mediated stimulation has been reported for the hepatic
      acute-phase response, for cytokine secretion, expression of cytokine/chemokine
      receptors, and for the pro-inflammatory mediator, macrophage migration inhibition
      factor. It seems clear that the long-held clinical view that GCs act solely as
      anti-inflammatory agents needs to be re-assessed. Varying doses of GCs do not
      lead simply to varying degrees of inflammation suppression, but rather GCs can
      exert a full range of effects from permissive to stimulatory to suppressive.

PMID- 15242424
TI  - Arginine vasopressin and serum nitrite/nitrate concentrations in advanced
      vasodilatory shock.
AB  - BACKGROUND: Arginine-vasopressin (AVP) can successfully stabilize hemodynamics in
      patients with advanced vasodilatory shock. It has been suggested that inhibition
      of cytokine-induced nitric oxide production may be an important mechanism
      underlying AVP-induced vasoconstriction. Therefore, serum concentrations of
      nitrite/nitrate (NOx), the stable metabolite of nitric oxide, were measured in
      patients suffering from advanced vasodilatory shock treated with either AVP in
      combination with norepinephrine (NE) or NE alone. METHODS: This trial was a
      separate study arm of a previously published prospective, randomized, controlled
      study on the effects of AVP in advanced vasodilatory shock. Thirty-eight patients
      were prospectively randomized to receive a combined infusion of AVP (4 U h(-1))
      and NE, or NE infusion alone. Serum NOx concentrations were measured at baseline,
      24, and 48 h after randomization. The increase in mean arterial pressure during
      the first hour after study enrollment was documented in all patients. RESULTS: No
      difference in NOx concentrations was found between groups throughout the study
      period. AVP patients demonstrated a significantly greater increase in mean
      arterial pressure than NE patients (22 +/- 10 vs. 5 +/- 9 mmHg; P < 0.001). The
      magnitude of pressure response to AVP was not correlated with NOx concentrations
      before start of AVP infusion (Pearson's correlation coefficient, -.009; P =
      0.971). CONCLUSION: Cardiovascular effects of AVP infusion in advanced
      vasodilatory shock are not mediated by a clinically relevant reduction in serum
      NOx concentrations. Therefore, hemodynamic improvement of patients in advanced
      vasodilatory shock during continuous infusion of AVP has to be attributed to
      other mechanisms than inhibition of nitric oxide synthase. In addition, the
      magnitude of pressure response to AVP is not correlated with baseline
      concentrations of NOx.

PMID- 15242425
TI  - Effectiveness and efficiency of intensive care medicine: variable costs in
      different diagnosis groups.
AB  - BACKGROUND: To establish the effectiveness of ICU treatment and the efficiency in
      the use of resources in patients stratified according to 10 diagnosis and two
      levels-of-care. To propose strategies aimed at reducing costs and improving
      efficiency in each patient group. METHODS: Multicentre prospective observational
      study. ICUs enrolled two cohorts of up to 10 consecutive patients with ICU stay
      >/= 48 h. Each with one of these diagnoses: trauma, brain-trauma, brain
      hemorrhage, stroke, acute-on-chronic-obstructive-pulmonary disease, lung
      injury/acute respiratory distress syndrome, heart failure, and
      scheduled/unscheduled abdominal surgery. The presence of active-life support
      divides high from low level-of-care treatments. Variable ICU costs were collected
      daily (bottom-up) for 21 days. We evaluated effectiveness (hospital survival) and
      efficiency (hospital-survivors variable-cost as a ratio of overall cost).
      RESULTS: Forty-two Italian general ICUs recruited 529 patients in 5 months. Mean
      ICU variable-costs significantly differed with diagnosis and level-of-care. Costs
      were positively affected by ICU length-of-stay, by duration of active-treatment.
      Outcome variably influenced costs. Medians of variable-costs per patient (1715
      Euro) and patient-groups efficiencies (60.7%) identified four possible
      combinations between (low and high) cost and (low and high) efficiency groups.
      Moreover, efficiency was better than effectiveness in stroke, brain-hemorrhage
      and trauma, while it was worse in heart failure, acute-on-COPD or acute-lung
      injury. Overall ICU cost attributed only to survivors ranged from 699 (scheduled
      surgical) to 5906 (unscheduled surgical) Euro. Cost of non-survivors distributed
      to all patient was between 95 (scheduled-surgical) to 1633 (unscheduled-surgical)
      Euro. CONCLUSIONS: Analysis of variable patient-specific cost was used as a tool
      to assess intensive care performance in patient subgroups with different
      diagnosis and levels-of-care.

PMID- 15242426
TI  - The use and safety of transoesophageal echocardiography in the general ICU -- a
      minireview.
AB  - BACKGROUND: The efficacy of transoesophageal echocardiography (TEE) has been
      evaluated predominantly in medical and cardiac surgical ICUs. This article
      reviews the pertinent literature and evaluates the impact of TEE in a general
      surgical ICU. METHODS: Twenty studies on TEE in the ICU were evaluated for
      complications, indications, diagnostic, therapeutic, and surgical impact on
      patient management. Diagnostic impact was defined as identification of the
      underlying cardiovascular pathology, therapeutic impact as changes in patient
      management and surgical impact as indication for operative procedures. In
      addition, we reviewed the TEE reports and patient charts of 216 critically ill
      patients in a 16-bed multidisciplinary surgical ICU at our university hospital,
      who underwent a TEE for differential diagnosis of hemodynamic instability from
      July 1995 to December 1998 to assess the impact of TEE on patient management in a
      general surgical ICU. RESULTS: The diagnostic, therapeutic and surgical impact in
      a total of 2,508 patients ranged from 44 to 99% (weighted mean 67.2%), 10-69%
      (36.0%), and 2-29% (14.1%), respectively. The complication rate was 2.6%, with no
      examination related mortality. In our series in a general surgical ICU, a
      diagnostic, therapeutic and surgical impact was inferred in 191 (88.4%), 148
      (68.5%) and 12 (5.6%) patients, respectively. Adverse effects were observed in
      5.6%. CONCLUSION: TEE is safe, well-tolerated and useful in the management of
      critically ill patients. This applies as well for hemodynamically unstable
      patients in a general surgical ICU.

PMID- 15242427
TI  - Changes in cerebral oxygenation during cold (28 degrees C) and warm (34 degrees
      C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH
      stat) in patients undergoing coronary artery bypass graft surgery.
AB  - BACKGROUND: Impaired cerebral oxygenation, which is reflected by measuring
      jugular bulb oxygenation, is thought to play an important role in the development
      of neurological injury after cardiac operations with cardiopulmonary bypass
      (CPB). The effects of cardiopulmonary temperature and blood gas strategy on
      cerebral oxygenation are not fully appreciated. METHODS: Sixty patients were
      randomly allocated into four equal groups (cold alpha-stat, cold pH-stat, warm
      alpha-stat and warm pH-stat) to compare the effect of these perfusion strategies
      on cerebral oxygenation monitored by jugular bulb oximetry [jugular bulb oxygen
      saturation (SjO(2)) and arterial-jugular bulb oxygen content difference
      (AjDO(2))]. Jugular bulb oxygen saturation and AjDO(2) were measured before CPB,
      after 5, 20, 40 min on CPB, at start and end of rewarming, 5 min before the end
      of CPB and 10 min after CPB. Two-way analysis of variance was used to model the
      lowest SjO(2) and highest AjDO(2) during CPB, with CPB temperature and blood gas
      management as contributing factors. RESULTS: Significant changes in SjO(2) were
      only related to the type of blood gas management, with no significant difference
      between warm and cold CPB patients. In addition, during rewarming, desaturation
      (SjO(2) </= 50%) occurred in seven patients of 30 in the alpha-stat groups and in
      one patient of 30 in the pH-stat groups (P = 0.021), and in five patients of 30
      in the cold groups vs. three of 30 in the warm groups (P = 0.434). However, no
      significant changes were found in the highest AjDO(2) between the four groups.
      CONCLUSION: Cold CPB failed to offer any further brain protection in terms of
      better preservation of cerebral oxygenation than warm CPB. Therefore, warm CPB
      (34 degrees C) with different blood gas strategies appears to be a satisfactory
      alternative to cold CPB (28 degrees C).

PMID- 15242428
TI  - Pulmonary net release of tissue-type plasminogen activator during porcine primary
      and secondary acute lung injury.
AB  - BACKGROUND: Tissue-type plasminogen activator (tPA) is a key mediator of
      fibrinolysis. Matching of pulmonary perfusion and ventilation is a critical
      denominator of oxygenation in acute lung injury (ALI). This study investigates
      pulmonary venoarterial plasma tPA gradients in association with acute ALI induced
      by bronchoalveolar lavage (BAL) and endotoxinemia (ETX). METHODS: Twenty-one
      anaesthetized, ventilated pigs were allocated to control (CTRL, n=5),
      bronchoalveolar saline lavage (BAL, n=8) or infusion of Escherichia coli
      endotoxin (ETX, n=8). Total tPA was analyzed in plasma (ELISA calibrated for
      porcine tPA). The inflammatory response was assessed by TNFa levels (ELISA). All
      variables were assessed at baseline and 2 h following ALI. RESULTS:
      Bronchoalveolar lavage and ETX induced similar increases in pulmonary shunt
      whereas pulmonary vascular resistance was significantly more increased in ETX
      animals. Cardiac output remained stable in BAL animals but decreased in ETX
      animals. The pulmonary venoarterial tPA plasma gradient increased in ETX animals,
      yielding a positive pulmonary net flux of tPA, which was absent in BAL animals.
      TNFalpha levels increased in ETX, but not in BAL, animals. A significant
      correlation was observed between TNFalpha and tPA plasma levels in ETX animals.
      All variables remained unchanged in CTRL animals. CONCLUSION: Plasma changes of
      tPA levels support a pulmonary release of tPA in early experimental ALI induced
      by acute ETX but not lavage, and are related to the inflammatory response.
      Despite increased vascular fibrinolytic capacity in ETX animals, pulmonary
      dysfunction was not different from BAL animals. The results demonstrate the close
      relation between inflammation and coagulation in early ALI.

PMID- 15242429
TI  - Pulmonary gas distribution during ventilation with different inspiratory flow
      patterns in experimental lung injury -- a computed tomography study.
AB  - BACKGROUND: There is still controversy about the optimal inspiratory flow pattern
      for ventilation of patients with acute lung injury. The aim of this study was to
      compare the effects of pressure-controlled ventilation (PCV) with a decelerating
      inspiratory flow with volume-controlled ventilation (VCV) with constant
      inspiratory flow on pulmonary gas distribution (PGD) in experimentally induced
      ARDS. METHODS: Sixteen adult sheep were randomized to be ventilated with PCV or
      VCV after surfactant depletion by repeated bronchoalveolar lavage. Positive end
      expiratory pressure (PEEP) was increased in a stepwise manner from zero end
      expiratory pressure (ZEEP) to 7, 14 and 21 cm H(2)O in hourly intervals.
      Respiratory rate, inspiration-to-expiration ratio and tidal volume were kept
      constant. Central hemodynamics, gas exchange and airway pressures were measured.
      Electron beam computed tomographic (EBCT) scans of the entire lungs were
      performed at baseline (preinjury) and each level of end-expiratory pressure
      during an inspiratory and expiratory hold maneuver. The lungs were three
      dimensionally reconstructed and volumetric assessments were made separating the
      lungs into four subvolumes classified as overinflated, normally aerated, poorly
      aerated and nonaerated. RESULTS: Pressure-controlled ventilation led to a
      decrease in peak airway pressure and an increase in mean airway pressure. No
      differences between groups were found regarding plateau pressures, hemodynamics
      and gas exchange. Recruitment, defined as a decrease in expiratory lung volume
      classified as nonaerated, was similar in both groups and predominantly associated
      with PEEP. Overinflated lung volumes were increased with PCV. CONCLUSIONS: In
      this model of acute lung injury, ventilation with decelerating inspiratory flow
      had no beneficial effects on PGD when compared with ventilation with constant
      inspiratory flow, while the increase in overinflated lung volumes may raise
      concerns regarding potential ventilator-associated lung injury.

PMID- 15242430
TI  - Aminotransferases after experimental pneumoperitoneum in dogs.
AB  - BACKGROUND: Laparoscopic surgery has rapidly become a popular and widely used
      technique. Elevated intra abdominal pressure due to gas insufflation for
      laparoscopic surgery may result in a number of local and systemic effects on the
      organism. The effects of pneumoperitoneum on the cardiovascular and respiratory
      system are well known today, but very few studies have been carried out on the
      consequences of pneumoperitoneum on hepatic integrity. The aim of the present
      study was to assess changes in aminotransferases, bilirubin and prothrombin time
      after pneumoperitoneum in dogs. METHODS: The effects of different levels and
      duration of intra abdominal pressure and different gases on liver function test
      were investigated in dogs. The levels of aspartate aminotransferase, alanine
      aminotransferase, total and direct bilirubin, and prothrombin time, according to
      the duration and the level of pneumoperitoneum and gas, were measured at 6, 12,
      24 and 48 h of desufflation. RESULTS: The levels of total bilirubin, direct
      bilirubin and prothrombin time showed no significant alteration. A statistically
      significant (P < 0.01) elevation of aspartate aminotransferase and alanine
      aminotransferase was recorded in the group of animals with higher intra abdominal
      pressure and longer duration of pneumoperitoneum. They returned to normal values
      within 48 h. CONCLUSION: Transient elevation of hepatic transaminases occurred
      after laparoscopic surgery, but they returned to normal values within 48 h. These
      increases were more prominent with higher and longer intra abdominal pressures
      irrespective of the type of insufflated gas. Alteration in aminotransferases was
      not associated with any clinical signs of hepatic dysfunction in experimental
      animals.

PMID- 15242431
TI  - Early bioavailability of paracetamol after oral or intravenous administration.
AB  - BACKGROUND: Paracetamol is a peripherally acting analgesic commonly used in
      multimodal post-operative pain management to reduce the need for more potent
      analgesics with their unwanted side-effects. The dose and optimal galenical form
      for achieving analgesic concentrations is not well defined. The primary aim of
      this pilot project was to study the early bioavailability for two fixed doses of
      orally administrated paracetamol and one dose of intravenous propacetamol, all of
      which were given after minor surgery. METHODS: Thirty-five patients undergoing
      day surgery were divided into five groups, seven patients each. Groups received
      either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol
      tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol
      tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma
      concentration of paracetamol during the first 80 min after administration.
      RESULTS: Within 40 min, intravenous propacetamol gave a median plasma paracetamol
      concentration of 85 micromol/l (range 65-161) and decreased thereafter. After
      oral administration, median plasma paracetamol concentration increased with
      increasing dose and time, but there were huge inter-individual differences at all
      time points studied. At 80 min after oral paracetamol the median plasma
      concentrations were 36 and 129 micromol/l for the 1- and 2-g groups,
      respectively, with an overall range between 0 and 306 micromol/l. CONCLUSION:
      Oral administration of paracetamol as part of multimodal pain management
      immediately post-operatively resulted in a huge and unpredictable variation in
      plasma concentration compared with the intravenous administration.

PMID- 15242432
TI  - Can chronic poststernotomy pain after cardiac valve replacement be reduced using
      thoracic epidural analgesia?
AB  - BACKGROUND: The aim of our study was to evaluate the use of thoracic epidural
      analgesia (TEA) in acute pain management after cardiac valve replacement and
      determine if the incidence of chronic pain related to the sternotomy was reduced
      by the use of TEA. This patient group was chosen to exclude pain related to the
      use of the internal mammary artery and angina pectoris. METHODS: Patients
      scheduled for elective cardiac valve replacement were offered TEA. A match
      control group was selected. Epidural catheter placement, complications and
      postoperative neurological state were noted for both groups. Eighteen months
      postoperatively, a questionnaire was sent out concerning pain management, wound
      discomfort and pain. RESULTS: Forty-nine patients were included. The TEA group
      consisted of 35 patients. At 18 months' follow up, 37% from the TEA group and 21%
      from the control group had pain or discomfort related to the sternum (NS). Two in
      the TEA group had severe pain. CONCLUSION: We found in our small material that
      TEA provided excellent analgesia in the peri- and postoperative period, but we
      did not find a protective effect of TEA on chronic poststernotomy pain, neither
      weak pain nor severe pain.

PMID- 15242433
TI  - Intrathecal morphine provides effective and safe analgesia in children after
      cardiac surgery.
AB  - BACKGROUND: The purpose of this prospective, randomized, blinded to observer
      study was to assess the analgesic effect and safety of intrathecal morphine (ITM)
      in post-operative pain control in children after heart surgery with a sternotomy
      incision. METHODS: Eighty children, 3-55 kg in body weight, undergoing elective
      cardiac surgery with opioid-based anaesthesia were randomly divided into two
      treatment groups to receive either 20 micrograms/kg ITM at induction of
      anaesthesia or control. To standardize the protocol for administration of post
      operative rescue intravenous morphine boluses and infusion (20-60
      micrograms/kg/h), the Cardiac Analgesic Assessment Scale (CAAS) was used.
      RESULTS: Nine patients were excluded from the study after randomization. Thirty
      five patients were enrolled to the ITM group and 36 to the control group. The
      groups were similar for demographics and intra-operative clinical
      characteristics. The mean time for the first intravenous morphine dose from ITM
      administration or equivalent time zero in the control group was significantly
      longer (P = 0.003) in the ITM group compared with the control group (12.3 vs. 8.7
      h). Time from Paediatric Intensive Care Unit (PICU) admission to the start of
      intravenous morphine was also significantly longer (P = 0.01) in the ITM group
      (6.0 vs. 3.4 h). The total intravenous morphine consumption over the mean 19 post
      operative hours was significantly lower (P = 0.03) in the ITM group. However, the
      use of ITM did not result in earlier extubation or earlier discharge from the
      PICU. Of the 35 patients who received ITM at induction of anesthesia, 20% (n = 7)
      did not require any additional morphine in the PICU compared with three out of 36
      control group patients. This did not reach statistical significance. The
      incidence of adverse events was low in both groups. CONCLUSIONS: An ITM dose of
      20 micrograms/kg had a significant (P = 0.03) intravenous morphine-sparing effect
      after cardiac surgery. Effective analgesia was observed for 12 h after
      administration of intrathecal morphine.

PMID- 15242434
TI  - Is a double-injection technique superior to a single injection in posterior
      subgluteal sciatic nerve block?
AB  - BACKGROUND AND OBJECTIVES: Currently, no information is available on the effects
      of a double-injection technique on onset time and efficacy following subgluteal
      sciatic nerve blockade. We hypothesized that the success rate and time to onset
      of subgluteal nerve block following a double-injection technique would be
      superior to that after a single injection. METHODS: Fifty ASA I or II patients
      undergoing foot or ankle surgery randomly received a single or double injection
      subgluteal sciatic nerve block. Group S (n=25) received a single injection of 30
      ml of 0.75% ropivacaine to the sciatic nerve. In Group D (n = 25), 15 ml of the
      same solution was injected to each sciatic nerve component. Completion of sensory
      and motor blockade, and patient acceptance, was evaluated by a blinded
      anesthesiologist. RESULTS: Complete sensory and motor blockade of the foot was
      achieved faster with the double injection (7.4 [5.9-8.8] min and 12.3 [10.4-14.2]
      min, respectively) than with the single-injection technique (12.5 [10.7-14.3] min
      and 18.8 [16.7-21.0] min, respectively) (P<0.001 and P<0.001, respectively).
      Success rate and acceptance were similar in both groups. Severe or moderate
      discomfort during the procedure was less frequent after a single injection (P =
      0.013). CONCLUSIONS: Both the single- and double-injection technique for
      subgluteal sciatic nerve blockade resulted in acceptable anesthesia in most
      patients. The double injection generated a faster onset of anesthesia than the
      single injection. However, the double-injection technique caused more patient
      discomfort during establishment of the nerve block.

PMID- 15242435
TI  - Efficacy of the A-line AEP monitor as a tool for predicting successful insertion
      of a laryngeal mask during sevoflurane anesthesia.
AB  - BACKGROUND: The use of clinical signs for assessing depth of anesthesia is
      unreliable during periods with little noxious stimulation. A patient may appear
      adequately anesthetized at one moment at a given level of stimulation, but may
      later, when facing other more intense stimuli, show signs of insufficient
      anesthesia. In order to prevent under- or overdosing of anesthetics, an
      anesthesia depth monitor that is able to predict responses to noxious stimulation
      would therefore be useful. Auditory evoked potentials (AEP) is one of several
      physiological parameters under investigation. The method has been improved by
      rapid extraction and conversion of the AEP curve into an index (A-Line ARX Index
      = AAI). We aimed to determine the clinically required depth of anesthesia,
      measured by the A-line AEP Monitor, for at least 90% probability of acceptable
      insertion conditions for a laryngeal mask airway (LMA). METHODS: We studied 112
      patients anesthetized by mask with increasing concentration of sevoflurane in
      oxygen. The monitor was programmed to give an alarm at AAI between 15 and 40
      according to randomization. When the alarm sounded, the end-expiratory
      sevoflurane concentration was recorded and the LMA inserted. Insertion conditions
      were assessed by an observer blinded to the AAI. RESULTS: The ED(95) and
      prediction probability (P(K)) for AAI were 14.5 (CI 7.4-21.6) and 0.76 (0.66
      0.86), respectively, while the ED(95) and P(K) for expiratory sevoflurane
      concentration were 4.36% (CI 3.73-4.98) and 0.95 (0.91-0.99). CONCLUSIONS: AAI
      indicates the level of depth of anesthesia necessary for acceptable laryngeal
      mask insertion conditions. End-expiratory sevoflurane concentration was the
      better predictor.

PMID- 15242436
TI  - Nitrous oxide increases the incidence of bowel distension in patients undergoing
      elective colon resection.
AB  - BACKGROUND: Nitrous oxide rapidly inflates gas-filled spaces such as the
      intestines; but whether the resulting bowel distension is clinically important
      remains unclear. We therefore tested the hypothesis that nitrous oxide produces
      clinically important bowel distension. METHODS: Patients scheduled for colon
      resection were anesthetized with isoflurane and 35% oxygen and randomly assigned
      to 65% nitrous oxide (n = 175) or 65% nitrogen in air (n = 169). At the end of
      surgery, blinded surgeons rated the degree of bowel distension as none, mild,
      moderate, or severe. Patients reported pain, and nausea and vomiting (PONV) 2 h
      after surgery. Data are reported as means (SD). P < 0.05 was statistically
      significant. RESULTS: Morphometric and demographic data were similar in the
      groups. The duration of surgery was 3.0 (1.2) h in the nitrous oxide group and
      3.4 (1.5) h in the air group (P = 0.017). Postoperative self-reported pain scores
      (visual analog scale, 0-100 mm) were greater in the nitrous oxide group (43 [30]
      mm) than in the air group (35 [31] mm, P = 0.018). Although the incidence of PONV
      was similar in the groups, VAS scores for nausea were significantly greater in
      the nitrous oxide group (P = 0.040). Moderate-to-severe bowel distension was
      observed in 23% of nitrous oxide patients, but in only 9% of patients in the air
      group (P < 0.001). The number-needed-to-harm for moderate or severe bowel
      distension from nitrous oxide was thus seven. CONCLUSIONS: Our results suggest
      that avoiding nitrous oxide administration during prolonged bowel operations will
      minimize bowel distension and possibly reduce postoperative pain related to it.

PMID- 15242437
TI  - Anaesthesia in day case laparoscopic female sterilization: a comparison of two
      anaesthetic methods.
AB  - BACKGROUND: Laparoscopic sterilization (LS) in women is a procedure frequently
      carried out in a day case setting. The purpose of the study was to measure
      postoperative pain, nausea and vomiting (PONV), the incidence of unplanned
      overnight admissions and patient satisfaction with two different anaesthetic
      methods. METHODS: From August 1997 to January 1999 the LS patients were
      anaesthetized with propofol + fentanyl/alfentanil, N2O and atracurium, and from
      January 1999 to end of 2001 they were given TIVA with propofol + remifentanil.
      Postoperative pain was managed with standardized high doses of paracetamol and
      NSAID in both groups. Data were collected from hospital records and from
      questionnaires given to all the patients. RESULTS: Six hundred and eighty-one
      women were sterilized. There were no significant differences in postoperative
      pain between the two groups, with 8.2 and 12.1 per cent, respectively,
      experiencing severe pain. Significantly fewer patients experienced moderate or
      severe postoperative nausea after the introduction of remifentanil anaesthesia
      (3.3 vs. 11.7%, P = 0.001). Eleven patients (1.8%) were admitted overnight, with
      no difference between the two groups. 94.5% and 96.3% of the patients were either
      satisfied or very satisfied with their treatment (P = 0.50). CONCLUSION: Both
      anaesthetic methods provide equally good postoperative pain relief, few unplanned
      admissions and a high degree of patient satisfaction when combined with
      postoperative paracetamol and NSAID. Patients anaesthetized with remifentanil and
      propofol have less postoperative nausea.

PMID- 15242438
TI  - Effects of neuromuscular-blocking drugs in rats in vivo: direct measurements in
      the diaphragm and tibialis anterior muscle.
AB  - BACKGROUND: Effects of neuromuscular-blocking drugs are often investigated in
      rodents using both the diaphragm in vitro and the tibialis anterior muscle in
      vivo. Differences in the properties of these muscles cannot be neglected. We
      evaluated the neuromuscular effects of drugs on the rat diaphragm in vivo in
      comparison with the tibialis anterior muscle, directly measuring twitch tension
      with a force transducer. METHODS: Respectively using sternotomy and an approach
      via the gluteal space, transducers were attached to the diaphragm and the
      tibialis anterior muscle. Phrenic and sciatic nerves were stimulated
      supramaximally by single square pulses to record isometric contraction of
      muscles. Pancuronium, vecuronium, or rocuronium was infused continuously at a
      rate adjusted repeatedly until stable tension was obtained. Effective doses for
      50% (ED 50) and 90% (ED 90) depression of tension were calculated, using a
      cumulative infusion dosing method. RESULTS: Isometric contraction of the
      diaphragm could be recorded despite movements of the heart and lungs. For all
      three drugs, both mean ED 50 and ED 90 were more than twice as large for the
      diaphragm as for the tibialis anterior (P<0.05). In addition, slopes of dose
      response curves for the diaphragm were significantly less steep than those of the
      tibialis anterior for the three drugs. CONCLUSION: Neuromuscular-blocking effects
      on the diaphragm can be recorded in vivo. According to direct contractile force
      measurement, the diaphragm is more resistant to non-depolarizing neuromuscular
      blocking drugs than the tibialis anterior muscle.

PMID- 15242439
TI  - Adrenaline administration during cardiopulmonary resuscitation: poor adherence to
      clinical guidelines.
AB  - BACKGROUND: Adrenaline does not appear to improve the outcome after cardiac
      arrest in clinical trials in spite of beneficial effects in experimental studies.
      The objective of this study was to determine whether adrenaline was administered
      in accordance with advanced cardiac life support (ACLS) guidelines during adult
      cardiopulmonary resuscitation (CPR). METHODS: From 15 January to 31 December
      2000, all patients at Uppsala University Hospital in whom CPR was attempted were
      registered prospectively. The duration of CPR was documented in the register and
      the total dose of adrenaline was retrieved retrospectively from patient records.
      From these data the average interval between adrenaline doses was calculated.
      RESULTS: Data for evaluation of the between-dose interval of adrenaline was
      available in 53 of 107 registered cardiac arrests. In 68% (36/53) the average
      between-dose interval was longer than the 3-5 min recommended in the guidelines,
      and 8% (4/53) received no adrenaline. The median interval between adrenaline
      doses during CPR was 6.5 min (25th-75th percentile: 5.1-10.4). Adherence to
      guidelines was lower in out-of-hospital cardiac arrest than in in-hospital
      cardiac arrest (P = 0.01). CONCLUSIONS: In the majority of cases adrenaline did
      not appear to be administered according to current ACLS guidelines.

PMID- 15242440
TI  - Rapid reversal of global left ventricular dysfunction after accidental injection
      of 0.75 mg epinephrine in a 20-year-old patient.
AB  - We report an accidental injection of epinephrine before spinal anaesthesia in a
      20-year-old patient who subsequently developed immediate myocardial ischemia and
      global left ventricular dysfunction (ejection fraction of 20%). Hemodynamic
      status dramatically improved after nitroglycerin, calcium antagonists, acetyl
      salicylic acid and unfractionated heparin injections. Over 24 h, patient's
      ejection fraction fully recovered without kinetic abnormality.

PMID- 15242441
TI  - Subcutaneous emphysema following severe vomiting after emerging from general
      anesthesia.
AB  - Postoperative nausea and vomiting-related subcutaneous emphysema is an unexpected
      complication, especially after uneventful surgery and anesthesia. Here we report
      and discuss two cases of subcutaneous emphysema following severe retching and
      vomiting which resolved spontaneously after several days.

PMID- 15242442
TI  - Anesthetic management for separation of craniopagus twins.
AB  - We report the anesthetic management of a case of separation of craniopagus twins
      with unbalanced cross circulation and one twin with renal dysfunction. After
      intravenous induction, anesthesia was maintained with isoflurane inhalation and
      propofol infusion. Twin A survived but Twin B died after the surgery. The
      anesthetic problems during the operation are discussed.

PMID- 15242443
TI  - Sequential combined spinal-epidural anesthesia for cesarean section in a woman
      with a double-outlet right ventricle.
AB  - The number of women with complex cyanotic heart disease reaching childbearing age
      is continuously increasing. For anesthesiologists, management of this 'new'
      obstetric population is particularly challenging. We report the case of a
      parturient with a palliated double-outlet right ventricle, who underwent a
      cesarean section at 34 weeks with low-dose sequential combined spinal-epidural
      anesthesia with patient-controlled epidural postoperative analgesia. Anesthetic
      considerations and specific limitations of invasive monitoring are discussed,
      along with a review of recent literature on maternal and neonatal complications
      associated with pregnancies in women with cyanotic congenital heart disease.

PMID- 15242444
TI  - Decreasing the incidence of post-dural puncture headache.

PMID- 15242445
TI  - Airway management in a high-risk infant with multiple congenital anomalies and
      difficult airway.

PMID- 15242446
TI  - Two cases of atrioventricular junctional rhythm induced by administration of
      regional injection of epinephrine.

PMID- 15242447
TI  - Anaesthetic management of unexpected subglottic stenosis in an achondroplasic
      dwarf.

PMID- 15242448
TI  - Hearing loss following general anesthesia.

PMID- 15242449
TI  - Updated perspectives on emerging vibrios associated with human infections.
AB  - This review describes the ecological, clinical and epidemiological features of
      emerging vibrios and discusses what laboratory methods are being used for the
      detection of pathogenic vibrios in clinical, environmental and food samples.
      After selecting articles illustrative of the current scientific research on
      pathogenic vibrios, the review focuses on the need for better insight into the
      risk factors of emerging infections to establish adequate prevention procedures.

PMID- 15242450
TI  - Quantitative RT-PCR for the enumeration of noroviruses (Norwalk-like viruses) in
      water and sewage.
AB  - AIMS: Aims of investigation: (i) develop a quantitative RT-PCR for noroviruses
      and (ii) evaluate it on environmental samples. METHODS AND RESULTS: Noroviruses
      in environmental water samples were concentrated by
      adsorption/elution/flocculation. Sewage was processed by clarification and
      protein flocculation. Norovirus-specific cDNA produced by primer-directed reverse
      transcription of extracted RNA was amplified by LightCycler and accumulation of
      product monitored by observation of fluorescence induced by the incorporation of
      SYBR Green. Absolute quantitation of product was achieved by construction of
      standard curves using quantitative standards produced by cloning a modified
      sequence of the 3'-region of the forward norovirus primer. Reaction specificity
      was confirmed by analysis of product melting curves. CONCLUSIONS: Sewage was
      found to contain up to 1.8 x 10(6) norovirus cDNA copies per 100 ml and effluent
      contained up to 1.7 x 10(6) copies per 10 l. Marine bathing water and
      recreational river waters also contained noroviruses. Sample inhibition was
      detected to varying degrees in most sample types. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study will enable quantitative comparisons be made of samples from
      different locations and treatment processes, and inform the debate on the
      revision of the EU Bathing Water Directive; it will have important implications
      for the analysis of samples derived from different aquatic matrices, and from
      foods.

PMID- 15242451
TI  - High-level gene expression in Lactobacillus plantarum using a pheromone-regulated
      bacteriocin promoter.
AB  - AIMS: To use promoters and regulatory genes involved in the production of the
      bacteriocin sakacin P to obtain high-level regulated gene expression in
      Lactobacillus plantarum. METHODS AND RESULTS: In a plasmid containing all three
      operons naturally involved in sakacin P production, the genes encoding sakacin P
      and its immunity protein were replaced by the aminopeptidase N gene from
      Lactococcus lactis (pepN) or the beta-glucuronidase gene from Escherichia coli
      (gusA). The new genes were precisely fused to the start codon of the sakacin P
      gene and the stop codon of the immunity gene. This set-up permitted regulated
      (external pheromone controlled) overexpression of both reporter genes in L.
      plantarum NC8. For PepN, production levels amounted to as much as 40% of total
      cellular protein. CONCLUSIONS: Promoters and regulatory genes involved in
      production of sakacin P are suitable for establishing inducible high-level gene
      expression in L. plantarum. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      describes a system for controllable gene expression in lactobacilli, giving some
      of the highest expression levels reported so far in this genus.

PMID- 15242452
TI  - Assessment of ciliates in the sheep rumen by DGGE.
AB  - AIMS: This work was carried out to develop a rapid molecular profiling technique
      to screen ciliate populations in the rumen of sheep. METHODS AND RESULTS: DGGE
      was used to study the ciliate diversity in the rumen of sheep. There was
      considerable variation between sheep which were co-housed, and fed the same diet.
      However, no difference in the major banding patterns was detected, when samples
      were collected from a single sheep sampled at different points. Following dietary
      changes, use of a pair-wise comparison of lanes, demonstrated that although there
      was still diversity between the ciliate population of sheep, the effects as a
      result of dietary changes were greater. CONCLUSIONS: The technique generated
      molecular profiles which are sufficiently different to allow comparison between
      samples, and to permit molecular ecological studies on the rumen ciliate
      population. SIGNIFICANCE AND IMPACT OF THE STUDY: The outcome of this study means
      that ciliate diversity in the rumen may now be studied by those unfamiliar with
      morphological identification of these organisms.

PMID- 15242453
TI  - Rapid and quantitative detection of the microbial spoilage in chicken meat by
      diffuse reflectance spectroscopy (600-1100 nm).
AB  - AIMS: To evaluate the feasibility of visible and short-wavelength near-infrared
      (SW-NIR) diffuse reflectance spectroscopy (600-1100 nm) to quantify the microbial
      loads in chicken meat and to develop a rapid methodology for monitoring the onset
      of spoilage. METHODS AND RESULTS: Twenty-four prepackaged fresh chicken breast
      muscle samples were prepared and stored at 21 degrees C for 24 h. Visible and SW
      NIR was used to detect and quantify the microbial loads in chicken breast muscle
      at time intervals of 0, 2, 4, 6, 8, 10, 12 and 24 h. Spectra were collected in
      the diffuse reflectance mode (600-1100 nm). Total aerobic plate count (APC) of
      each sample was determined by the spread plate method at 32 degrees C for 48 h.
      Principal component analysis (PCA) and partial least squares (PLS) based
      prediction models were developed. PCA analysis showed clear segregation of
      samples held 8 h or longer compared with 0-h control. An optimum PLS model
      required eight latent variables for chicken muscle (R = 0.91, SEP = 0.48 log CFU
      g(-1)). CONCLUSIONS: Visible and SW-NIR combined with PCA is capable of
      perceiving the change of the microbial loads in chicken muscle once the APC
      increases slightly above 1 log cycle. Accurate quantification of the bacterial
      loads in chicken muscle can be calculated from the PLS-based prediction method.
      SIGNIFICANCE AND THE IMPACT OF THE STUDY: Visible and SW-NIR spectroscopy is a
      technique with a considerable potential for monitoring food safety and food
      spoilage. Visible and SW-NIR can acquire a metabolic snapshot and quantify the
      microbial loads of food samples rapidly, accurately, and noninvasively. This
      method would allow for more expeditious applications of quality control in food
      industries.

PMID- 15242454
TI  - Evaluation of Cryptosporidium parvum oocyst recovery efficiencies from various
      filtration cartridges by electrochemiluminescence assays.
AB  - AIMS: To evaluate four types of filtration cartridges for their capacities,
      efficiency for capture and release of Cryptosporidium parvum oocysts for
      detection. METHODS AND RESULTS: Filtration cartridges included in this evaluation
      were IDEXX Filta-Max, Gelman Envirochek HV, Corning CrypTest, and Filterite
      Sigma+. Various dosages of C. parvum oocysts were spiked into water samples with
      a wide range of turbidity (10-50 NTU). Electrochemiluminescence assays were
      employed to enumerate viable or total number of C. parvum oocysts in these
      eluates. Among the cartridges tested, Filta-Max consistently showed higher oocyst
      recovery efficiency, especially with large volume, highly turbid water samples.
      CONCLUSIONS: Filta-Max filter is the best performer because of its higher oocyst
      recovery efficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: The overall
      sensitivities of various C. parvum oocyst detection assays in water samples can
      be improved if highly efficient oocyst recovery filtration cartridges such as
      Filta-Max are incorporated in sample preparation.

PMID- 15242455
TI  - Co-composting of PAH-contaminated soil with poultry manure.
AB  - AIMS: To investigate the effects of co-composting poultry manure with soil
      contaminated with different concentrations of polycyclic aromatic hydrocarbons
      (PAHs), on the degradation of selected PAHs in a static-pile compost system.
      METHODS: Mispah form (Food & Agricultural Organisation, FAO : lithosol) soil
      contaminated with PAHs was co-composted with poultry manure for 19 months. The
      soil was mixed with wood chips in a ratio of 1:1 to improve aeration and then
      mixed with poultry manure in a ratio of 4:1. A data logger measured temperature
      monthly. Residual concentrations of selected PAHs in the compost were determined
      monthly by gas chromatography/flame ionisation detection (GC/FID). Moisture, pH,
      ash content and C:N ratios were also monitored monthly. Microbial activity was
      measured by measuring CO(2) evolution. CONCLUSIONS: The results obtained in this
      experiment have shown that co-composting poultry manure with PAH-contaminated
      soil is capable of removing large concentrations of high molecular weight PAH
      from contaminated soil to levels below 1 mg kg(-1) in 19 months. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The paper adds to the body of knowledge necessary for the
      development of a cost effective technology for the remediation of soil
      contaminated with high molecular weight PAHs by providing information on the
      behaviour of selected PAHs and factors such as nutrient ratio, temperature and pH
      during composting.

PMID- 15242456
TI  - Decontamination effect of electrolysed NaCl solutions on carp.
AB  - AIMS: To evaluate the efficacy of electrolysed NaCl solutions (EW) for
      disinfecting bacterial isolates from carp, and the potential application of EW to
      reducing the bacterial load in whole carp and carp fillets. METHODS AND RESULTS:
      EW was produced by using a two-compartment batch-type electrolysed apparatus.
      Pure cultures (in vitro), whole carp (skin surface) and carp fillets were treated
      with EW to detect its antimicrobial effects. The anodic solution [EW (+)]
      completely inhibited growth of the isolates. Furthermore, dipping the fish
      samples in EW (+) reduced the mean total count of aerobic bacteria on the skin of
      whole carp and in fillets by 2.8 and 2.0 log(10), respectively. The cathodic
      solution [EW (-)] also reduced growth of the isolates from carp by ca 1.0
      log(10). Moreover, the total counts of aerobic bacteria in whole carp (on the
      skin) and fillets were reduced by 1.28 and 0.82 log(10), respectively.
      CONCLUSIONS: EW (+) has a strong bactericidal effect on bacteria isolated from
      carp. SIGNIFICANCE AND IMPACT OF THE STUDY: Treatment with EW (+) could extend
      the shelf life of these fish.

PMID- 15242457
TI  - Chlorophyllin protects HEp-2 cells from nuclear fragmentation induced by
      poliovirus.
AB  - AIMS: Chlorophyllin (CHLN) is a synthetic derivative of chlorophyll that
      possesses antimutagenic activity against several environmental contaminants. In
      the present study, CHLN was assayed for its capacity to prevent nuclear
      fragmentation (NF) in HEp-2 cells infected with poliovirus. METHODS AND RESULTS:
      CHLN was assayed at concentrations of 0.5 and 2.5 microg ml(-1), and NF was
      monitored using the comet assay and acridine orange staining. We demonstrated
      that CHLN reduced the percentage of NF in poliovirus-infected HEp-2 cells, when
      cells were treated with drug before infection or exposed continuously to drug.
      However, the highest degree of protection was achieved when the virus was exposed
      to CHLN before infection followed by protocol where infected cultures were
      continuously exposed to the drug after infection. CONCLUSIONS: It is suggested
      that CHLN primarily binds to the virus which inhibits cell penetration, thereby
      maintaining nuclear integrity. SIGNIFICANCE AND IMPACT OF THE STUDY: Considering
      that CHLN has several beneficial properties and no significant toxic effects in
      humans and animals, it would be an ideal candidate drug to test for antiviral
      activity.

PMID- 15242458
TI  - Streptomyces sp. strain isolated from river water has high bisphenol A
      degradability.
AB  - AIMS: We report the identification of the bisphenol A (BPA) biodegradability in
      Streptomyces sp. strain isolated from river water. METHODS AND RESULTS: The water
      samples spiked with BPA (1 mg l(-1)) and the culture solution of Streptomyces sp.
      strain were placed at 30 degrees C for 10 days and were analysed by high
      performance liquid chromatography. A half-life for BPA degradation was between 3
      and 4 days. The removal rate of BPA was >90% for 10 days. CONCLUSIONS: These
      results show that the Streptomyces sp. strain isolated from river water has high
      BPA degradability. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this
      is the first report of BPA degradation by Streptomyces sp. strain.

PMID- 15242459
TI  - Characterization of a protease of a feather-degrading Microbacterium species.
AB  - AIMS: To characterize a new feather-degrading bacterium. METHODS AND RESULTS: The
      strain kr10 producing a high keratinolytic activity when cultured on native
      feather broth was identified as Microbacterium sp., based on phenotypical
      characteristics and 16S rDNA sequence. The bacterium presented optimum growth and
      feather-degrading activity at pH 7.0 and 30 degrees C. Complete feather
      degradation was achieved during cultivation. The keratinase was partially
      purified by gel filtration chromatography. It was optimally active at pH 7.0 and
      55 degrees C. The enzyme was inhibited by 1,10-phenanthroline, EDTA, p
      chloromercuribenzoic acid, 2-mercaptoethanol and metal ions like Hg(2+), Cu(2+)
      and Zn(2+). SIGNIFICANCE AND IMPACT OF THE STUDY: A new Microbacterium sp. strain
      was characterized presenting high feather-degrading activity, which appears to be
      associated to a metalloprotease-type keratinase. This micro-organism has enormous
      potential for use in biotechnological processes involving keratin hydrolysis.

PMID- 15242460
TI  - Comparison of primers for the detection of Salmonella enterica serovars using
      real-time PCR.
AB  - AIMS: To evaluate the specificity and sensitivity of PCR primers for the
      detection of Salmonella enterica in a real-time PCR assay using pure cultures.
      METHODS AND RESULTS: Unenriched whole cells in sterile water were used as
      template for each PCR. SYBR Green dye was used for the nonspecific detection of
      dsDNA. The real-time PCR detection limits of five previously published primer
      sets used in conventional PCR applications were not below 3 x 10(3) CFU per
      reaction (rxn). A new primer set, Sen, was designed, which detected Salm.
      enterica Newport down to 6 CFU rxn(-1) in one case, and gave an average detection
      limit of 35 CFU rxn(-1) over three separate runs. CONCLUSIONS: Primers originally
      designed for end-point PCR did not have adequate specificity or sensitivity
      compared with those specifically designed for real-time PCR. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study emphasizes the importance of evaluating real-time
      PCR primer sets in pure cultures prior to testing in field samples. This study
      will benefit other researchers in selecting an appropriate primer set for real
      time PCR detection of Salm. enterica.

PMID- 15242461
TI  - Virucidal activity of the new disinfectant monopercitric acid.
AB  - AIMS: The virucidal efficacy of monopercitric acid (MPCA) was evaluated against
      the enveloped vaccinia virus as well as the nonenveloped adenovirus type 2 and
      poliovirus type 1. The results were compared with that obtained with peracetic
      acid (PAA). METHODS AND RESULTS: In the virucidal suspension test without and
      with protein burden, all viruses were inactivated by 0.5% MPCA within 0.5 min or
      by 0.1% MPCA within 5 min as measured by a >10(4)-fold reduction in virus titres.
      For MPCA, there was a better virucidal efficacy than for PAA which inactivated
      all viruses included in the test within 15-30 min at a concentration of 0.2%.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The high virucidal activity, short exposure
      times, and nontoxic by-products seem to make MPCA suitable as disinfectant for
      medical use and should warrant further investigation.

PMID- 15242462
TI  - Manipulating the pyruvate dehydrogenase bypass of a multi-vitamin auxotrophic
      yeast Torulopsis glabrata enhanced pyruvate production.
AB  - AIMS: To investigate the relationship between the activity of pyruvate
      dehydrogenase (PDH) bypass and the production of pyruvate of a multi-vitamin
      auxotrophic yeast Torulopsis glabrata. METHODS AND RESULTS: Torulopsis glabrata
      CCTCC M202019, a multi-vitamin auxotrophic yeast that requires acetate for
      complete growth on glucose minimum medium, was selected after nitrosoguanidine
      mutagenesis of the parent strain T. glabrata WSH-IP303 screened in previous study
      [Li et al. (2001) Appl. Microbiol. Biotechnol. 55, 680-685]. Strain CCTCC M202019
      produced 21% higher pyruvate than the parent strain and was genetically stable in
      flask cultures. The activities of the pyruvate metabolism-related enzymes in
      parent and mutant strains were measured. Compared with the parent strain, the
      activity of pyruvate decarboxylase (PDC) of the mutant strain CCTCC M202019
      decreased by roughly 40%, while the activity of acetyl-CoA synthetase (ACS) of
      the mutant increased by 103.5 or 57.4%, respectively, in the presence or absence
      of acetate. Pyruvate production by the mutant strain CCTCC M202019 reached 68.7 g
      l(-1) at 62 h (yield on glucose of 0.651 g g(-1)) in a 7-l jar fermentor.
      CONCLUSIONS: The increased pyruvate yield in T. glabrata CCTCC M202019 was due to
      a balanced manipulation of the PDH bypass, where the shortage of cytoplasmic
      acetyl-CoA caused by the decreased activity of PDC was properly compensated by
      the increased activity of ACS. SIGNIFICANCE AND IMPACT OF THE STUDY: Manipulating
      the PDH bypass may provide an alternative approach to enhance the production of
      glycolysis-related metabolites.

PMID- 15242463
TI  - Levels of zoonotic agents in British livestock manures.
AB  - AIMS: To determine the prevalence and levels of zoonotic agents in livestock
      wastes. METHODS AND RESULTS: A proportionally weighted survey was undertaken and
      livestock waste samples analysed quantitatively for Escherichia coli O157,
      pathogenic Listeria, Salmonella, Campylobacter, Giardia and Cryptosporidium. A
      significant proportion of wastes contained at least one zoonotic agent.
      Relationships were found between dry matter content and the presence and levels
      of some zoonotic agents. CONCLUSIONS: British livestock wastes contain measurable
      levels of the zoonotic agents that cause most cases of gastroenteritis in the UK.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Animal wastes are disposed of by spreading
      to agricultural land used for the production of crops and livestock grazing. As
      British wastes are contaminated with significant levels of zoonotic agents, the
      practice may represent a way for pathogens to travel further up the food chain.

PMID- 15242464
TI  - Isolation of bacteriophages from the oral cavity.
AB  - AIMS: To isolate bacteriophages lytic for oral pathogens from human saliva,
      dental plaque and mature biofilms constituted from saliva-derived bacteria.
      METHODS AND RESULTS: Saliva and dental plaque samples from healthy volunteers and
      from patients with gingivitis and periodontitis were examined for the presence of
      lytic bacteriophage using a panel of oral pathogens and bacteria isolated from
      the samples. Samples were also enriched for bacteriophage using static culture
      techniques and mature biofilms. A limited number of samples contained
      bacteriophage particles that were visualized using electron microscopy. Cultures
      yielded phage infecting non-oral bacteria (Proteus mirabilis) but no
      bacteriophage specific for recognized oral pathogens were found. Some micro
      organisms from the oral microflora elaborated antibacterial substances that
      inhibited growth of other residents of the oral cavity. CONCLUSIONS: Unlike other
      ecosystems, the composition of the oral cavity does not appear to be heavily
      influenced by interactions between bacteriophages and their hosts. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Bacteriophage for control of oral infections may need to
      be obtained from other sources. Antibacterial substances derived from some
      members of the oral microflora warrant investigation as potential antibiotics.

PMID- 15242465
TI  - The outcome of physical symptoms with treatment of depression.
AB  - OBJECTIVE: This study examined the prevalence, impact on health-related quality
      of life (HRQoL), and outcome of physical symptoms in depressed patients during 9
      months of antidepressant therapy. DESIGN: Open-label, randomized, intention-to
      treat trial with enrollment occurring April through November 1999. SETTING:
      Thirty-seven primary care clinics within a research network. PATIENTS: Five
      hundred seventy-three depressed patients started on one of three selective
      serotonin reuptake inhibitors (SSRIs) by their primary care physician and who
      completed a baseline interview. INTERVENTIONS: Patients were randomized to
      receive fluoxetine, paroxetine, or sertraline. MEASUREMENTS AND MAIN RESULTS:
      Outcomes assessed included physical symptoms, depression, and multiple domains of
      HRQoL. Prevalence of physical symptoms was determined at baseline and after 1, 3,
      6, and 9 months of treatment. Stepwise linear regression models were used to
      determine the independent effects of physical symptoms and depression on HRQoL
      domains. Of the 14 physical symptoms assessed, 13 were present in at least a
      third to half of the patients at baseline. Each symptom showed the greatest
      improvement during the initial month of treatment. In contrast, depression
      continued to show gradual improvement over a 9-month period. Physical symptoms
      had a predominant effect on pain (explaining 17% to 18% of the variance),
      physical functioning (13%), and overall health perceptions (13% to 15%).
      Depression had the greatest impact on mental (26% to 45%), social (14% to 32%),
      and work functioning (9% to 32%). CONCLUSIONS: Physical symptoms are prevalent in
      depressed patients and initially improve in the first month of SSRI treatment.
      Unlike depression, however, improvement in physical symptoms typically plateaus
      with minimal resolution in subsequent months.

PMID- 15242466
TI  - Violence, mental health, and physical symptoms in an academic internal medicine
      practice.
AB  - OBJECTIVE: To assess how physical and/or sexual intimate partner violence (IPV),
      child abuse, and community violence relate to long-term mental and physical
      problems; to examine the overlap between different forms of violence and the
      impact of experiencing multiple forms of violence. DESIGN: Cross-sectional
      survey. SETTING: Three general internal medicine practices affiliated with an
      academic medical center. PARTICIPANTS: English-speaking women aged 25 to 60.
      MEASUREMENTS: Telephone or in-person interview and chart review. RESULTS: One
      hundred seventy-four women completed interviews. A majority of participants
      experienced more than one form of violence. In separate multivariate analyses,
      each form of violence was associated with depressive symptoms or with at least 6
      chronic physical symptoms, after adjustment for demographic factors and substance
      abuse. The degree of association with health outcomes was similar for each form
      of violence (odds ratio [OR], 2.4 to 3.9; P < .003). The association with chronic
      physical symptoms remained significant for IPV (OR, 3.3; P < .002) and community
      violence (OR, 3.4; P < .003), even after adjustment for depression and
      posttraumatic stress disorder. There were dose-response relationships between the
      number of forms of violence experienced and the odds of depressive symptoms and
      the odds of multiple chronic physical symptoms. CONCLUSIONS: Multiple types of
      victimizations may contribute to patients' current mental health and physical
      problems. Research or clinical protocols that only focus on one form of violence
      may underestimate the complexity of women's experiences and needs.

PMID- 15242467
TI  - Efficacy of bupropion for relapse prevention in smokers with and without a past
      history of major depression.
AB  - BACKGROUND: This study evaluated the efficacy of bupropion for relapse prevention
      in smokers with and without a past history of major depressive disorder. Changes
      in depressive symptoms were also examined. DESIGN: Data were gathered
      prospectively from a randomized, double-blind relapse prevention trial of
      bupropion conducted at five study sites. A total of 784 smokers (54% female, 97%
      white) were enrolled. Using the Structured Clinical Interview for Depression, 17%
      of the subjects reported a past history of major depressive disorder at baseline.
      All subjects received open-label bupropion SR (300 mg/d) for 7 weeks. Subjects
      abstinent from smoking at the end of 7 weeks (N = 429) were randomized to
      bupropion SR (300 mg/d) or placebo for the remainder of the year and followed for
      1 year off medication. The primary outcome measures were median time to relapse
      to smoking and the 7-day point-prevalence smoking abstinence rate. Self-reported
      abstinence from smoking was verified by expired air carbon monoxide. The Beck
      Depression Inventory was used to assess depressive symptoms at baseline and at
      weeks 8 and 12. RESULTS: Median time to relapse did not differ by past history of
      major depressive disorder. Bupropion was associated with higher point-prevalence
      smoking abstinence at the end of medication compared to placebo (P = .007),
      independent of a past history of major depressive disorder. Moreover, change in
      depressive symptoms during the double-blind phase did not differ for those with
      and without a past history of major depressive disorder. CONCLUSIONS: Extended
      use of bupropion for relapse prevention is effective for smokers with and without
      a history of major depression.

PMID- 15242468
TI  - Randomized trial examining the effect of two prostate cancer screening
      educational interventions on patient knowledge, preferences, and behaviors.
AB  - OBJECTIVE: To assess the effect of video and pamphlet interventions on patient
      prostate cancer (CaP) screening knowledge, decision-making participation,
      preferences, and behaviors. DESIGN: Randomized, controlled trial. SETTING: Four
      midwestern Veterans Affairs medical facilities. PATIENTS/PARTICIPANTS: One
      thousand, one hundred fifty-two male veterans age 50 and older with primary care
      appointments at participating facilities were randomized and 893 completed follow
      up. INTERVENTIONS: Patients were randomized to mailed pamphlet, mailed video, or
      usual care/control. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed by phone
      survey 2 weeks postintervention included a 10-item knowledge index; correct
      responses to questions on CaP natural history, treatment efficacy, the prostate
      specific antigen (PSA)'s predictive value, and expert disagreement about the PSA;
      whether screening was discussed with provider; screening preferences; and PSA
      testing rates. Mean knowledge index scores were higher for video (7.44; P = .001)
      and pamphlet (7.26; P = .03) subjects versus controls (6.90). Video and pamphlet
      subjects reported significantly higher percentages of correct responses relative
      to controls to questions on CaP natural history (63%, 63%, and 54%,
      respectively); treatment efficacy (19%, 20%, and 5%), and expert disagreement
      (28%, 19%, and 8%), but not PSA accuracy (28%, 22%, and 22%). Pamphlet subjects
      were more likely than controls to discuss screening with their provider (41% vs
      32%; P = .03) but video subjects were not (35%; P = .33). Video and pamphlet
      subjects were less likely to intend to have a PSA, relative to controls (63%,
      65%, and 74%, respectively). PSA testing rates did not differ significantly
      across groups. CONCLUSIONS: Mailed interventions enhance patient knowledge and
      self-reported participation in decision making, and alter screening preferences.
      The pamphlet and video interventions evaluated are comparable in effectiveness.
      The lower-cost pamphlet approach is an attractive option for clinics with limited
      resources.

PMID- 15242469
TI  - Prostate and colon cancer screening messages in popular magazines.
AB  - OBJECTIVES: To 1) compare the number of articles published about prostate, colon,
      and breast cancer in popular magazines during the past 2 decades, and 2) evaluate
      the content of in-depth prostate and colon cancer screening articles identified
      from 1996 to 2001. DESIGN: We used a searchable database to identify the number
      of prostate, colon, and breast cancer articles published in three magazines with
      the highest circulation from six categories. In addition, we performed a
      systematic review on the in-depth (> or = 2 pages) articles on prostate and colon
      cancer screening that appeared from 1996 through 2001. RESULTS: Although the
      number of magazine articles on prostate and colon cancer published in the 1990s
      increased compared to the 1980s, the number of articles is approximately one
      third of breast cancer articles. There were 36 in-depth articles from 1996 to
      2001 in which prostate or colon cancer screening were mentioned. Over 90% of the
      articles recommended screening. However, of those articles, only 76% (25/33; 95%
      confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of
      screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were
      only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to
      45%) of the articles provided all the necessary information needed for the reader
      to make an informed decision. CONCLUSIONS: In-depth articles about prostate and
      colon cancer in popular magazines do not appear as frequently as articles about
      breast cancer. The available articles on prostate and colon cancer screening
      often do not provide the information necessary for the reader to make an informed
      decision about screening.

PMID- 15242470
TI  - Agreement of four competing guidelines on prevention of venous thromboembolism
      and comparison with observed physician practices: a cross-sectional study of
      1,032 medical inpatients.
AB  - OBJECTIVE: To assess the degree of agreement between four competing guidelines
      regarding the recommendation for prophylactic heparin therapy and to report to
      what extent actual practice agreed with or differed from the recommendations made
      before these guidelines were disseminated. DESIGN: Four French guidelines were
      applied to data from a cross-sectional study conducted before their
      dissemination. SETTING: Twenty-six medical units of a teaching and a nonteaching
      hospital. PATIENTS: One thousand thirty-two medical inpatients. MAIN
      MEASUREMENTS: Interguideline agreement rated by the kappa coefficient and
      percentage of patients receiving prophylactic heparin treatment. RESULTS: The
      percentage of patients requiring prophylactic treatment ranged from 35.4% to
      54.6% (overall kappa coefficient, 0.65 [0.63 to 0.68]), depending on the
      guideline. The four guidelines agreed in recommending prophylactic heparin
      treatment in 330 patients (32.0%). The corresponding rate of prophylactic
      treatment use was 57.0% (188/330). None of the guidelines recommended
      prophylactic heparin treatment in 385 patients (37.3%). The physicians did not
      order prophylactic treatment in 80.3% of these patients (309/385). The guidelines
      disagreed in recommending prophylactic treatment in 317 patients (30.7%). The
      corresponding rate of prophylactic treatment use was 32.8% (104/317). CONCLUSION:
      The four guidelines agreed in 69.3% of patients but physician practices were
      already quite appropriate in these patients before the guidelines were
      disseminated. Active dissemination of the guidelines can be expected to improve
      physician practices in the treatment of these patients, but likely with limited
      impact. In contrast, the four guidelines disagreed in 30.7% of patients. Further
      clinical trials are needed in this subgroup of patients.

PMID- 15242471
TI  - Barriers to patient-physician communication about out-of-pocket costs.
AB  - BACKGROUND: Though many patients and physicians believe that they should discuss
      out-of-pocket costs, research suggests that they infrequently do. OBJECTIVE: To
      examine barriers preventing patient-physician communication about out-of-pocket
      costs among study subjects recalling a time when they wanted to discuss these
      costs but did not do so. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      surveys of 133 general internists and 484 of their patients from 3 academic and
      18 community practices in a large midwestern metropolitan region. MEASUREMENTS:
      Patient- and physician-reported barriers to discussing out-of-pocket costs. MAIN
      RESULTS: Overall, 54 patients (11%) and 27 physicians (20%) were able to recall a
      specific time when they wanted to discuss out-of-pocket costs but did not do so.
      Among patients, a wide variety of barriers were reported including their own
      discomfort (19%), insufficient time (13%), a belief that their physician did not
      have a viable solution (11%), and concerns about the impact of discussions on
      quality of care (9%). Among physicians, the most common barriers reported were
      insufficient time (67%) and a belief that they did not have a solution to offer
      (19%). CONCLUSIONS: Efforts to promote discussions of out-of-pocket costs should
      emphasize the legitimacy of patients' concerns and brief actionable alternatives
      that physicians can take to address them.

PMID- 15242472
TI  - Creating a quality improvement elective for medical house officers.
AB  - The Accreditation Council on Graduate Medical Education (ACGME) requires that
      house officers demonstrate competencies in "practice-based learning and
      improvement" and in "the ability to effectively call on system resources to
      provide care that is of optimum value." Anticipating this requirement, faculty at
      a Boston teaching hospital developed a 3-week elective for medical house officers
      in quality improvement (QI). The objectives of the elective were to enhance
      residents' understanding of QI concepts, their familiarity with the hospital's QI
      infrastructure, and to gain practical experience with root-cause analysis and QI
      initiatives. Learners participated in three didactic seminars, joined hospital
      based QI activities, conducted a root-cause analysis, and completed a QI project
      under the guidance of a faculty mentor. The elective enrolled 26 residents in 3
      years. Sixty-three percent of resident respondents said that the elective
      increased their understanding of QI in health care; 88% better understood QI in
      their own institution.

PMID- 15242473
TI  - Will insured citizens give up benefit coverage to include the uninsured?
AB  - OBJECTIVE: To describe the willingness of insured citizens to trade off their own
      health benefits to cover the uninsured. DESIGN: Descriptive study of individual
      and group decisions and decision making using quantitative and qualitative
      methods. SETTING AND PARTICIPANTS: Twenty-nine groups of citizens (N = 282)
      residing throughout Minnesota. INTERVENTIONS: Groups participated in Choosing
      Healthplans All Together (CHAT), a simulation exercise in which participants
      choose whether and how extensively to cover health services in a hypothetical
      health plan constrained by limited resources. We describe individual and group
      decisions, and group dialogue concerning whether to allocate 2% of their premium
      to cover uninsured children in Minnesota, or 4% of their premium to cover
      uninsured children and adults. MEASUREMENTS AND MAIN RESULTS: While discussing
      coverage for the uninsured, groups presented arguments about personal
      responsibility, community benefit, caring for the vulnerable, social impact, and
      perceptions of personal risk. All groups chose to insure children; 22 of 29
      groups also insured adults. More individuals chose to cover the uninsured at the
      end of the exercise, after group deliberation, than before (66% vs 54%; P <
      .001). Individual selections differed from group selections more often for the
      uninsured category than any other. Nevertheless, 89% of participants were willing
      to abide by the health plan developed by their group. CONCLUSION: In the context
      of tradeoffs with their own health insurance benefits, groups of Minnesotans
      presented value-based arguments about covering the uninsured. All 29 groups and
      two thirds of individuals chose to contribute a portion of their premium to
      insure all children and most groups chose also to insure uninsured adults.

PMID- 15242474
TI  - Quality of preventive clinical services among caregivers in the health and
      retirement study.
AB  - We examined the association between caregiving for a spouse and preventive
      clinical services (self-reported influenza vaccination, cholesterol screening,
      mammography, Pap smear, and prostate cancer screening over 2 years and monthly
      self-breast exam) for the caregiver in a cross-sectional analysis of the Health
      and Retirement Study, a nationally representative sample of U.S. adults aged > or
      = 50 years (N = 11,394). Spouses engaged in 0, 1-14, or > or = 14 hours per week
      of caregiving. Each service was examined in logistic regression models adjusting
      for caregiver characteristics. After adjustment for covariates, there were no
      significant associations between spousal caregiving and likelihood of caregiver
      receipt of preventive services.

PMID- 15242475
TI  - Should aspirin be continued in patients started on warfarin?
AB  - BACKGROUND AND OBJECTIVE: Clinicians frequently face the decision of whether to
      continue aspirin when starting patients on warfarin. We performed a meta-analysis
      to characterize the tradeoffs involved in this common clinical dilemma. DATA
      SOURCES: Multiple computerized databases (1966 to 2003), reference lists of
      relevant articles, conference proceedings, and queries of primary authors. STUDY
      SELECTION: Randomized trials comparing warfarin plus aspirin versus warfarin
      alone. Studies with target international normalized ratios (INRs) <2 were
      excluded. DATA EXTRACTION: Two reviewers independently extracted baseline data
      and major outcomes: rates of thromboembolism, hemorrhage, and all-cause
      mortality. DATA SYNTHESIS: Nine studies met the inclusion criteria. Of the five
      that enrolled patients with mechanical heart valves, four used the same target
      INR in both groups, while one used a reduced target INR for the warfarin plus
      aspirin group. Pooling the results of the first four studies demonstrated that
      combination of warfarin plus aspirin significantly decreased thromboembolic
      events (relative risk [RR], 0.33; 95% confidence interval [CI], 0.19 to 0.58),
      increased major bleeding (RR, 1.58; 95% CI, 1.02 to 2.44), and decreased all
      cause mortality (RR, 0.43; 95% CI, 0.23 to 0.81) compared to warfarin alone. The
      one valve trial using a reduced INR in the warfarin plus aspirin group reported
      no difference in thromboembolic outcomes but found decreased major bleeding and a
      significant mortality benefit with combination therapy. Of the remaining trials,
      three evaluated a warfarin indication not routinely used in the United States
      (post-myocardial infarction), and the only trial that considered atrial
      fibrillation was terminated early due to inadequate enrollment. CONCLUSIONS: For
      mechanical heart valve patients, the benefits of continuing aspirin when starting
      warfarin therapy are clear. For other routine warfarin indications, there are not
      adequate data to guide this common clinical decision.

PMID- 15242476
TI  - Fostering professionalism in medical education: a call for improved assessment
      and meaningful incentives.
AB  - Increasing attention has been focused on developing professionalism in medical
      school graduates. Unfortunately, the culture of academic medical centers and the
      behaviors that faculty model are often incongruent with our image of
      professionalism. The need for improved role modeling, better assessment of
      student behavior, and focused faculty development is reviewed. We propose that
      the incentive structure be adjusted to reward professional behavior in both
      students and faculty. The third-year medicine clerkship provides an ideal
      opportunity for clinician-educators to play a leading role in evaluating,
      rewarding, and ultimately fostering professionalism in medical school graduates.

PMID- 15242477
TI  - The many faces of depression in primary care.

PMID- 15242478
TI  - Altruism and coverage of the uninsured.

PMID- 15242480
TI  - The role of culture and cross-cultural miscommunication in the perpetuation of
      disparities.

PMID- 15242483
TI  - Does antibody to hepatitis B surface antigen protect renal transplant patients
      from hepatitis B?

PMID- 15242484
TI  - Reasons for creation of permanent ileostomy for the management of idiopathic
      chronic constipation.
AB  - The aim of the present study was to examine the reasons for initiation of end
      ileostomy for management of intractable constipation over the last 35 years. A
      total of 62 patients with intractable constipation, on whom an end ileostomy was
      created during the period from 1966 to 2001, were recorded. The incidence of
      initiating a terminal ileostomy as a further surgical intervention to the total
      number of managed patients in examined studies varied from 2 to 25%. Preoperative
      unevaluated anal and rectal abnormalities formed the highest proportion compared
      with other reasons (65%, 40/62). A better understanding of the functional colonic
      and anorectal abnormalities may facilitate changes in surgical therapy.

PMID- 15242485
TI  - Hepatitis B virus infection after renal transplantation in the presence of
      antibody to hepatitis B surface antigen immunity.
AB  - BACKGROUND AND AIM: Hepatitis B virus (HBV) infection has been known to be
      hampered by immunity against hepatitis B surface antigen (HBsAg). However, HBV
      with mutations within the common antigenic epitope of HBsAg, the "a" determinant
      region, can escape from humoral immunity. Moreover, HBV infection by "a"
      determinant mutants in chronic HBV patients has been reported after renal
      transplantation. In the present study, the authors investigated HBV infection
      after renal transplantation despite passive immunization or resolved HBV
      infection. METHODS: A total of 1682 patients who underwent a renal transplant
      between 1979 and 1998 at the Severance Hospital, Yonsei University College of
      Medicine, Korea, were enrolled. The sequence of the HBV genome was analyzed from
      two patients with antibody to HBsAg (anti-HBs) immunity. RESULTS: Of 1682
      patients who were HBsAg negative before transplantation, 21 patients were found
      to be HBsAg positive, with elevated aspartate aminotransferase and alanine
      aminotransferase levels after transplantation. Interestingly, six of 21 (28.6%)
      patients were anti-HBs positive before the transplantation. Sequence analysis of
      the cloned HBV from two of six patients with anti-HBs immunity showed no evidence
      of significant mutations within the "a" determinant region, suggesting a wild
      type of HBV. Their donors were not exposed to HBV before transplantation (all HBV
      markers were negative). Seven deaths of 21 patients were ascribed to HBV-related
      complications. CONCLUSIONS: Regardless of anti-HBs immunity, HBV infection
      occurred in immunosuppressed patients in a high endemic area. The molecular
      mechanism and clinical impact of HBV infection after renal transplantation in
      patients with anti-HBs immunity should be further reappraised.

PMID- 15242486
TI  - Non-alcoholic steatohepatitis in type 2 diabetes mellitus.
AB  - BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is commonly associated
      with type 2 diabetes mellitus (DM). Prevalence of NASH in type 2 DM has not been
      well studied and there is an epidemic rise in type 2 DM in Asian and Western
      populations. Its association with chronic liver disease in the form of NASH makes
      it an important health problem. Hence we have studied its prevalence and
      correlation of biochemical parameters with histological grades of non-alcoholic
      fatty liver disease (NAFLD) in otherwise asymptomatic type 2 DM patients.
      METHODS: One hundred and forty-eight individuals were screened. Forty-eight
      individuals were excluded due to history of alcohol intake or liver disease as a
      result of other causes. One hundred non-alcoholic individuals with type 2 DM
      underwent abdominal ultrasonography (US abdomen). Forty-nine patients had
      evidence of fatty liver on US abdomen, and 32 of these 49 patients underwent
      liver biopsy. RESULTS: Four of 32 (12.5%) individuals had steatosis alone. Mild,
      moderate and severe NASH was present in 21/32 (65.5%), 4/32 (12.5%) and 3/32
      (9.35%), respectively. Fibrosis was present in 7/32 (21.8%) patients (four grade
      1 and three grade 3). There was no significant difference in body mass index
      (BMI), transaminase levels, serum cholesterol and triglyceride levels among
      patients with non-alcoholic fatty liver disease. CONCLUSION: We conclude that the
      prevalence of NASH is high in type 2 DM patients and liver biopsy is the only
      investigation to differentiate between non-alcoholic fatty liver and
      steatohepatitis.

PMID- 15242487
TI  - Optimal treatment strategy for elderly patients with hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: The age distribution of patients with hepatocellular
      carcinoma (HCC) now peaks at nearly 70 years in Japan and this is continually
      increasing. Whether such elderly patients with HCC aged 80 years or older should
      be treated, and if so, how they should be selected for treatment remains
      uncertain. The present study was undertaken to determine any differences in the
      clinical characteristics and prognostic features between patients with HCC aged
      80 years or older and those younger than 80 years of age. We also aimed to
      identify any significant variables in the prognosis of elderly patients with HCC
      aged 80 years or older. METHODS: Seven hundred and four patients with HCC,
      diagnosed during a 12-year period from January 1989 to December 2000, were
      categorized into two groups as follows: (i) 36 patients aged 80 years or older at
      the detection of HCC were defined as the elderly group and; (ii) 668 patients
      younger than 80 years of age were placed in the non-elderly group. Clinical
      variables were analyzed and compared between the two groups, and any significant
      variables in the prognosis were simultaneously determined. RESULTS: Regarding
      sex, viral markers, concentration of serum alpha-fetoprotein, diameter and number
      of tumors, Child's grade, presence of portal thrombosis, histology grade of HCC
      and any types of treatment, no significant difference was found between the two
      groups. The 1-year and 3-year survival rates in the elderly group (54.1 and
      28.1%, respectively) were not significantly different from those in the non
      elderly group (69.9 and 43.2%, respectively; P = 0.1053). The only significant
      factor in the prognosis in the elderly group was the presence of portal
      thrombosis, although a Child's grade of B or C was almost a significant factor
      with a P-value of 0.063. Tumor size measuring more than 3 cm in the greatest
      dimension, non-solitary tumor, Child's grade of B or C, and the presence of
      portal thrombosis were all found to be prognostic factors in the non-elderly
      group using a multivariate analysis. CONCLUSIONS: An advanced stage of HCC, not
      advanced age, influenced the survival rate in these elderly patients. Therefore,
      an optimal treatment strategy should be applied for elderly patients with HCC who
      demonstrate less prognostic factors in the same manner as that for non-elderly
      patients.

PMID- 15242488
TI  - Apoptotic pathway related to oval cell proliferation.
AB  - BACKGROUND AND AIM: Oval cells, liver stem cell-derived cells, are generated from
      the liver periportal region and spread into the parenchyma by an autocrine
      signaling pathway. The mechanism behind how oval cells take their place among
      packed silent hepatocytes, however, is not well understood. We hypothesized that
      apoptosis involves a decrease in hepatocytes surrounding oval cells. METHODS:
      Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in
      the liver. Apoptosis was assessed by measuring the activity of caspase-3, -8 and 
      9, and apoptosis-related molecules such as caspase-3, Fas, Fas-L and Bax were
      also assessed by immunohistochemical analysis and reverse transcriptase
      polymerase chain reaction (RT-PCR). Apoptosis was confirmed by TUNEL staining.
      Regarding antiapoptotic factors, nuclear factor-kappaB (NF-kappaB) DNA binding
      activity and proliferating cell nuclear antigen (PCNA) expression were examined.
      RESULTS: NF-kappaB elevated at the early stage of oval cell proliferation.
      Conversely, caspase activity increased after NF-kappaB elevation. The mRNA of
      caspase-3, Fas, Fas-L and Bax was induced during and after AAF/PH treatment.
      Immunohistochemically, oval cells lacked the expression of these proteins,
      whereas the hepatocytes, particularly those surrounding oval cells, expressed
      strongly. CONCLUSIONS: The present study suggests that the apoptosis in
      hepatocytes through both extrinsic and intrinsic pathways mediates oval cell
      proliferation.

PMID- 15242489
TI  - Prevalence of immune disturbances and chronic liver disease in family members of
      patients with primary biliary cirrhosis.
AB  - BACKGROUND AND AIMS: Primary biliary cirrhosis (PBC) has been reported in up to 4
      6% of first degree relatives of patients with the disease. In addition, immune
      abnormalities, including hypergammaglobulinemia, autoantibodies and increased
      frequency of autoimmune disorders, were reported in family members of PBC
      patients. The aim of the present study was to investigate the prevalence of PBC
      in relatives of patients with PBC, and to investigate the occurrence of chronic
      liver disease (CLD) and immune abnormalities in these subjects. METHODS: One
      hundred first degree relatives of 26 patients with PBC were interviewed and
      submitted to physical examination and determination of liver enzymes, gamma
      globulin, bilirubin and auto-antibodies, including antinuclear (ANA), antismooth
      muscle (SMA), antimitochondrial antibodies (AMA) by indirect immunofluorescence
      (IIF) and anti-M2 antibody by immunoblotting (IB). RESULTS: Immune disturbances
      were rarely observed in relatives of PBC patients. Higher gamma-globulin levels,
      SMA and ANA were detected in four, eight and two family members, respectively. In
      most subjects, these autoantibodies were either in low titers or associated with
      concurrent diseases. Only four relatives had extrahepatic autoimmune diseases and
      another eight exhibited other CLD. Primary biliary cirrhosis was detected in a
      sister of one patient. Additionally, two other relatives of PBC patients who
      tested negative for AMA by IIF showed reactivity for anti-M2 by IB. CONCLUSIONS:
      Immune disturbances, including ANA and SMA, are uncommon in family members of PBC
      patients. Conversely, anti-M2 antibodies and overt PBC do occur in relatives of
      PBC patients, even in Brazil where the disease is quite rare.

PMID- 15242490
TI  - Effects of pravastatin and bezafibrate on biliary lipid excretion and hepatic
      expression of Abcg5 and Abcg8 in the rat.
AB  - BACKGROUND AND AIM: Multidrug resistance associated gene product 2 (Mdr2) is
      believed to have a significant role in biliary cholesterol and phospholipid
      secretions. Both pravastatin and bezafibrate resulted in Mdr2 induction, but
      increased cholesterol secretion was observed only in pravastatin treatment. To
      explore the mechanism, the hepatic expression of genes that are responsible for
      the metabolism of the lipids was studied. METHODS: Rats were divided into three
      experimental groups: (i) the control group; (ii) the bezafibrate group, which was
      fed a diet containing 0.45% bezafibrate for 5 days; and (iii) the pravastatin
      group, which was fed a diet containing 0.1% pravastatin for 5 days. Serum,
      hepatic and biliary lipids were measured by colorimetric assays and hepatic mRNA
      related to lipid metabolism was studied by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: In the bezafibrate group biliary phospholipid
      secretion was increased although cholesterol secretion was not increased. In the
      pravastatin group, biliary cholesterol and phospholipid secretions were
      significantly increased. The biliary cholesterol/phospholipid ratio was decreased
      in the bezafibrate group, but the ratio did not change in the pravastatin group.
      Hepatic Mdr2, Abcg5 and Abcg8 mRNA expression was remarkably increased in the
      pravastatin group in comparison with the control group (184%, 264% and 247% of
      control value, respectively). In the bezafibrate group the hepatic gene
      expression of Mdr2 was increased (157% of control value), but there were no
      significant changes in hepatic Abcg5 and Abcg8 mRNA expression compared with the
      control group. CONCLUSIONS: Compared with Mdr2, Abcg5 and Abcg8 seem to be more
      essential transporters for biliary secretion of cholesterol. Pravastatin
      upregulated Abcg5/Abcg8 while bezafibrate did not, which appears to explain the
      different effects of these compounds on biliary lipid secretion.

PMID- 15242492
TI  - Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic
      prevalence, histological and clinical characteristics.
AB  - BACKGROUND AND AIM: Heterotopic gastric mucosal patch, which has a 0.1-10%
      frequency, is encountered when the cervical esophagus is examined carefully
      during endoscopy. In this study, we aimed to determine the prevalence of the
      patch in the cervical esophagus, to identify its macroscopic and histological
      characteristics and to evaluate demographic and clinical features. METHODS: Six
      hundred and sixty patients (317 male, 343 female; mean age 50.28 years, range 14
      90) with upper gastrointestinal symptoms had elective esophagogastroduodenoscopy
      and the cervical esophagus was examined for the patch during withdrawal of the
      endoscope. Biopsies were obtained from the antrum and the patch. Helicobacter
      pylori was assessed using an immunohistochemical method. RESULTS: The patch was
      found in 11 patients of 660, with a prevalence of 1.67%. Patch size ranged
      between 5 and 30 mm, appeared as a single patch in nine patients and as twin
      patches in two patients. Mean age and male : female ratio were not significantly
      different from the patient population without patches, but the female sex was
      predominant (three men, eight women; mean age 43.6 years, range 32-64). In five
      of 11 patients, the upper esophageal and laryngopharyngeal symptoms were
      remarkable. Eight patients in whom histological confirmation was carried out
      showed three fundic and five antral-type mucosa. Two of five patients with antral
      H. pylori also had the bacteria in the patch. H. pylori prevalence in the patch
      was 25%. CONCLUSION: Heterotopic gastric mucosal patches in the proximal
      esophagus should not be overlooked during endoscopy because they may lead to
      important complications in relation to their acid secretion, which may vary
      according to their parietal cell mass.

PMID- 15242491
TI  - Induction of a 72-kDa heat shock protein and protection against
      lipopolysaccharide-induced liver injury in cirrhotic rats.
AB  - BACKGROUND AND AIM: A 70-kDa heat shock protein (stress-inducible HSP70, HSP72)
      has been reported to be a cytoprotectant in a variety of organs. It has been
      reported that HSP72 protected non-cirrhotic rats against endotoxemia. However,
      its cytoprotective effect against endotoxemia in cirrhotic rats has not yet been
      studied. In this study, we investigated the cytoprotective effect of HSP72 on
      lipopolysaccharide (LPS)-induced liver injury in carbon tetrachloride (CCl(4))
      induced cirrhotic rats. METHODS: Liver cirrhosis was produced by an 8-week
      intraperitoneal injection of CCl(4) in male Sprague-Dawley rats. Expression of
      HSP72 was investigated using western blot analysis. Cirrhotic rats were given an
      intraperitoneal injection of LPS (10 mg/kg) with or without hyperthermia (42.5
      degrees C, 15 min) preconditioning. Liver injury was assessed biochemically
      (aspartate transaminase, alanine transaminase, bilirubin, lactate dehydrogenase,
      creatinine) and histologically. The plasma tumor necrosis factor (TNF)-alpha
      level was determined. RESULTS: Hyperthermia preconditioning induced a 4-fold
      increase in HSP72 in the cirrhotic rat liver. Pre-induction of HSP72 prevented
      LPS-induced liver injury, as evaluated using serum biochemical parameters and
      histology with reduced TNF-alpha response. CONCLUSION: These findings suggest
      that pre-induction of HSP72 may provide therapeutic strategies for Gram-negative
      sepsis-induced liver injury in liver cirrhosis.

PMID- 15242493
TI  - Efficacy of electrolyzed acid water in reprocessing patient-used flexible upper
      endoscopes: Comparison with 2% alkaline glutaraldehyde.
AB  - BACKGROUND AND AIM: Two percent glutaraldehyde, the most widely used liquid
      chemical germicide (LCG), may be hazardous to patients and medical personnel.
      Alternatives to glutaraldehyde, such as electrolyzed acid water (EAW), are being
      developed, but data from well-controlled studies with patient-used endoscopes are
      rare. The purpose of the present paper was to evaluate the high-level
      disinfection capability of EAW and compare it with glutaraldehyde. METHODS: A
      random sample of 125 endoscopes was collected immediately after upper endoscopic
      examination. After careful manual cleaning, endoscopes were divided into a
      glutaraldehyde and EAW group. After the disinfection procedure, samples from
      working channel (S-1), insertion tube (S-2), umbilical cord (S-3), and angulation
      knob (S-4) were taken and cultured. Another twenty endoscopes were experimentally
      contaminated with hepatitis B virus (HBV) and samples were collected after
      contamination (T-1), after manual cleaning (T-2), and after final disinfection (T
      3). Polymerase chain reaction (PCR) for HBV-DNA was performed. RESULTS: In the
      EAW group, culture-positive rates were 3.2% in S-1, 9.5% in S-2, 3.2% in S-3, and
      27.0% in the S-4 samples. There was no significant difference between the EAW and
      glutaraldehyde groups for all sampling sites. However, in both groups,
      disinfection of the angulation knobs (S-4) was less efficient than the others.
      For the T-1 site, HBV-DNA was detected from all of them, and in 95% (19/20) of T
      2. However, HBV-DNA was not detected from T-3 samples. CONCLUSIONS: Electrolyzed
      acid water is as efficient as glutaraldehyde in eliminating bacteria from patient
      used endoscopes. After disinfection procedures using both methods, HBV-DNA was
      not detected from any endoscopes experimentally contaminated with HBV-positive
      mixed sera. However, some bacteria may remain on the surface of the endoscopes.
      Therefore, more careful precleaning of the endoscopes may help achieve high-level
      disinfection in the clinical setting.

PMID- 15242494
TI  - Small bowel bacterial overgrowth is a common cause of chronic diarrhea.
AB  - BACKGROUND AND AIMS: Often a cause for chronic non-specific diarrhea (> or =3
      stools per day for more than 4 weeks) is not identified. Small bowel bacterial
      overgrowth (SBO) can occur without morphological damage and remains difficult to
      diagnose. Often diarrhea is treated empirically with antibiotics with a good
      response. The aims of the present study were first to investigate the prevalence
      of SBO in a consecutive series of patients with chronic diarrhea and second to
      compare the utility of duodenal fluid culture and (14)C-d-xylose breath/lactulose
      test in diagnosing SBO. METHODS: In the first study, the cause of chronic
      diarrhea was prospectively diagnosed in 87 subjects. In the second study, tests
      of SBO were compared in 18 subjects with chronic diarrhea and 15 subjects with
      reflux oesophagitis used as control subjects. Duodenal fluid was aspirated at
      endoscopy and cultured and later a (14)C-d-xylose breath/lactulose test was
      performed. RESULTS: In the first study, SBO was present in 48% of those with
      chronic diarrhea. In the second study, the diarrhea group had an average (range)
      stool frequency of 5.5 (3-10) per day and had normal duodenal biopsies. A total
      of 33%, 50%, 67% of subjects had SBO by duodenal culture alone, by a (14)C-d
      xylose breath/lactulose test alone and by a combination of both tests,
      respectively. In the control group, 0%, 13% and 13% had SBO by duodenal culture
      alone, by (14)C-d-xylose breath/lactulose test alone and by combination of tests,
      respectively. CONCLUSION: Small bowel bacterial overgrowth is a common (33-67%)
      cause of chronic diarrhea.

PMID- 15242495
TI  - Immune response in mouse experimental cholangitis associated with colitis induced
      by dextran sulfate sodium.
AB  - BACKGROUND AND AIM: Primary sclerosing cholangitis is frequently complicated by
      inflammatory bowel disease. Although many colitis models have been reported,
      little information has been obtained about complicated cholangitis. The aim of
      the present study was to determine whether hepatobiliary disorders occur in mice
      experimental colitis, and to clarify the underlying mechanisms. METHODS: The CD-1
      mice were fed standard chow with or without dextran sulfate sodium in the
      drinking water, followed by histological examination of the liver and colon.
      Mononuclear cells were isolated from these organs, and cytokine production was
      assessed. The CD4/CD8 ratio and the population of natural killer T (NKT) cells
      were analyzed by flow cytometry. RESULTS: Inflammatory cell infiltration and
      focal necrosis in the liver were found in 33% of treated mice. In treated mice,
      the CD4/CD8 ratio increased in the liver, whereas no such change was found in the
      colon. Also an increase of interferon-gamma and a decrease of interleukin-4
      production were observed. The NKT cell population showed transient changes in the
      liver and colon. CONCLUSIONS: Hepatobiliary disorders were complicated with
      experimental colitis in CD-1 mice. Immunological findings indicate a T-helper-1
      dominant underlying mechanism, and NKT cells may play a pathogenic role in this
      model. This model may help to elucidate the relationship between hepatic and
      colonic inflammations.

PMID- 15242496
TI  - Mutational spectrum of K-ras oncogene among Indian patients with gallbladder
      cancer.
AB  - BACKGROUND AND AIM: Gallbladder cancer (GBC) is a common abdominal malignancy in
      India with an obscure etiology. However, long-standing stones and chronic
      infection in gallbladder have been suspected as possible etiologic factors. As
      carcinogenesis complicating chronic inflammation proceeds through the stages of
      dysplasia and metaplasia, mutation in the K-ras gene may be an important marker
      for GBC. The aim of the present study was to detect K-ras mutation in cytological
      smears from GBC. METHODS: Malignant cells were marked on slides of cytological
      smears obtained from 39 patients with cytologically proven GBC. Marked cells were
      scraped off and DNA was extracted. Polymerase chain reaction coupled with
      restriction fragment length polymorphism (RFLP) analysis was performed to detect
      the point mutation in codon 12 of the K-ras gene. RESULTS: Mutation in codon 12
      of K-ras oncogene was detected in eight (38%) of 21 PCR amplified samples by this
      technique. Six of eight specimens with K-ras (codon 12) mutation corresponded to
      coexisting gallstone disease. Five patients with K-ras (codon 12) mutation were
      found to have stage IV malignancy. CONCLUSIONS: Mutation in codon 12 of the K-ras
      oncogene occurs in more than one-third of GBC in northern India. Its detection
      from fine-needle aspirates may prove useful as an adjunct to cytological
      examination. The presence of this mutation suggests that chronic inflammation may
      play an etiologic role in gallbladder carcinogenesis.

PMID- 15242497
TI  - Autonomic responses to heartburn induced by esophageal acid infusion.
AB  - BACKGROUND AND AIM: Studies have shown that altered visceral perception and lower
      pain thresholds in patients with symptomatic gastroesophageal reflux disease
      (GERD) and non-cardiac chest pain. Autonomic changes associated with the
      perception of heartburn in patients with GERD are poorly understood. METHODS: A
      total of 12 GERD patients (six male, six female; mean age 37.2 +/- 2.7 years) and
      12 controls (five male, seven female; mean age 32.8 +/- 2.2 years) were studied.
      The study protocol included a 20-min water infusion (6 mL/min), and 20-min acid
      infusion (0.1 N HCl, 6 mL/min). Spectral analysis of heart-rate variability (HRV)
      was used to assess autonomic functioning. The measured HRV indices included the
      power in the low-frequency (LF) band (0.04-0.15 Hz) reflecting sympathetic tone,
      and power in the high-frequency (HF) band (0.15-0.5 Hz) reflecting vagal tone,
      and the LF/HF ratio as an indicator of sympathovagal balance. RESULTS: The GERD
      group experienced more heartburn than controls with acid infusion. Between-group
      comparisons showed no significant changes in LF band power in any period. The HF
      band power was significantly lower in GERD patients during all infusion periods.
      The LF/HF ratio was significantly larger in GERD patients. CONCLUSIONS: The
      perception of heartburn induced by esophageal acid infusion is associated with a
      simultaneous increase in sympathetic modulation in patients with GERD. The
      autonomic responses with esophageal acid infusion are significantly different
      between healthy subjects and GERD patients.

PMID- 15242498
TI  - Relationship of smoking and coffee and alcohol consumption with seroconversion to
      Helicobacter pylori: a longitudinal study in hospital workers.
AB  - BACKGROUND AND AIM: There are few data concerning the relationship between
      Helicobacter pylori seroconversion, and smoking habits and coffee and alcohol
      consumption. The aim of the present study was to investigate the relationship
      between smoking habits, coffee and alcohol consumption, and H. pylori
      seroconversion. METHODS: The data used were derived from a sample of 238 subjects
      (hospital employees) who were initially (on 1994) seronegative to H. pylori.
      These subjects were tested again 5 years later (1999). Information concerning
      smoking habits and coffee and alcohol consumption was collected by the use of a
      special questionnaire, which was completed by the same cohort of subjects in two
      different periods (1994 and 1999). Logistic regression was used to assess the
      relationship between H. pylori seroconversion and the aforementioned lifestyle
      factors. RESULTS: Neither smoking nor coffee consumption was significantly
      related to H. pylori seroconversion. Adjusted odds ratio for alcohol drinkers as
      compared with non-/occasional drinkers was 0.59 (95% confidence interval [CI]:
      0.31-1.16, P = 0.13). However, the odds ratio was significantly lower (0.26,
      95%CI: 0.07-0.95, P = 0.042) in subjects who reported moderate alcohol
      consumption at first (1994) examination, as compared with non-/occasional
      drinkers. Small and heavy drinking were not associated with H. pylori
      seroconversion. CONCLUSIONS: There is no significant relation between H. pylori
      seroconversion and smoking and coffee consumption. The present findings suggest
      that moderate alcohol consumption might be inversely associated with H. pylori
      seroconversion.

PMID- 15242499
TI  - Images of interest. Gastrointestinal: multiple endocrine neoplasia type I and
      duodenal gastrinomas.

PMID- 15242500
TI  - Images of interest. Gastrointestinal: esophagitis caused by alendronate.

PMID- 15242501
TI  - Images of interest. Hepatobiliary and pancreatic: choledochocele.

PMID- 15242502
TI  - Images of interest. Hepatobiliary and pancreatic: peritoneal dissemination
      mimicking liver metastases.

PMID- 15242503
TI  - Genetic disorders in pancreatitis.

PMID- 15242504
TI  - Endoscopic findings of adenocarcinoma arising from short-segment Barrett's
      esophagus.
AB  - Adenocarcinoma arising from short-segment Barrett's esophagus (SSBE) is rare in
      Japan, although the incidence of this condition is increasing in Western
      countries. Four cases of early adenocarcinoma arising from SSBE were diagnosed
      and treated at Niigata-prefectural Yoshida Hospital. All patients were male,
      variously 55, 71, 73 and 79 years of age. All four patients had long-term
      gastroesophageal reflux disease, although one patient had erosive esophagitis and
      three patients did not have erosive esophagitis. Three patients were diagnosed as
      having Helicobacter pylori-free stomach. All adenocarcinomas occurred close to
      the squamocolumnar junction. Patients with SSBE should undergo detailed
      endoscopic examination of the squamocolumnar junction in order to detect early
      adenocarcinoma arising from SSBE.

PMID- 15242505
TI  - Stellate-type scirrhous dysplastic nodules in liver cirrhosis: identical to focal
      nodular hyperplasia-like nodules?

PMID- 15242506
TI  - Silent colorectal carcinoma and pyogenic liver abscess.

PMID- 15242507
TI  - Significance of combined spiral 3-D computed tomography angiogram and pneumocolon
      for primary mesenteric stromal tumor.

PMID- 15242508
TI  - Carcinosarcoma of the liver: a case report with interesting histologic and
      immunohistochemical features.

PMID- 15242509
TI  - Case of HELLP syndrome with an unusual presentation.

PMID- 15242510
TI  - Kupffer cell function of hepatocellular adenoma: pulse sequence effects in
      superparamagnetic iron oxide-enhanced magnetic resonance imaging.

PMID- 15242511
TI  - Rhabdomyolysis triggered by cytomegalovirus infection in a heart transplant
      patient on concomitant cyclosporine and atorvastatin therapy.

PMID- 15242512
TI  - Prevalence and characterization of integrons in blood culture Enterobacteriaceae
      and gastrointestinal Escherichia coli in Norway and reporting of a novel class 1
      integron-located lincosamide resistance gene.
AB  - BACKGROUND: Class 1 integrons contain genetic elements for site-specific
      recombination, capture and mobilization of resistance genes. Studies
      investigating the prevalence, distribution and types of integron located
      resistance genes are important for surveillance of antimicrobial resistance and
      to understand resistance development at the molecular level. METHODS: We
      determined the prevalence and genetic content of class 1 integrons in
      Enterobacteriaceae (strain collection 1, n = 192) and E. coli (strain collection
      2, n = 53) from bloodstream infections in patients from six Norwegian hospitals
      by molecular techniques. Class 1 integrons were also characterized in 54 randomly
      selected multiresistant E. coli isolates from gastrointestinal human infections
      (strain collection 3). RESULTS: Class 1 integrons were present in 10.9% of the
      Enterobacteriaceae blood culture isolates of collection 1, all but one (S. Typhi)
      being E. coli. Data indicated variations in class 1 integron prevalence between
      hospitals. Class 1 integrons were present in 37% and 34% of the resistant blood
      culture isolates (collection 1 and 2, respectively) and in 42% of the resistant
      gastrointestinal E. coli. We detected a total of 10 distinct integron cassette
      PCR amplicons that varied in size between 0.15 kb and 2.2 kb and contained
      between zero and three resistance genes. Cassettes encoding resistance to
      trimethoprim and aminoglycosides were most common. We identified and
      characterized a novel plasmid-located integron with a cassette-bound novel gene
      (linF) located downstream of an aadA2 gene cassette. The linF gene encoded a
      putative 273 aa lincosamide nucleotidyltransferase resistance protein and
      conferred resistance to lincomycin and clindamycin. The deduced LinF amino acid
      sequence displayed approximately 35% identity to the Enterococcus faecium and
      Enterococcus faecalis nucleotidyl transferases encoded by linB and linB'
      CONCLUSIONS: The present study demonstrated an overall low and stable prevalence
      of class 1 integron gene cassettes in clinical Enterobacteriaceae and E. coli
      isolates in Norway. Characterization of the novel lincosamide resistance gene
      extends the growing list of class 1 integron gene cassettes that confer
      resistance to an increasing number of antibiotics.

PMID- 15242513
TI  - Dosage-dependent effects of permethrin-treated nets on the behaviour of Anopheles
      gambiae and the selection of pyrethroid resistance.
AB  - BACKGROUND: The evolution and spread of pyrethroid resistance in Anopheles
      gambiae s.s, the major malaria vector in sub-Saharan Africa, is of great concern
      owing to the importance of pyrethroid-treated nets in the WHO global strategy for
      malaria control. The impact of kdr (the main pyrethroid-resistance mechanism) on
      the behaviour of An. gambiae is not well understood. The objective of this study
      was to determine whether high or low doses of permethrin differ in their
      resistance-selection effects. METHODS: The effect of permethrin treatment was
      assessed under laboratory conditions using the tunnel test technique against
      susceptible, heterozygous and homozygous genotypes. Experimental huts trials were
      then carried out in Benin to assess the level of personal protection conferred by
      nets treated with a variety of permethrin concentrations and their impact on the
      selection for kdr allele. RESULTS: Tunnel tests showed that nets treated with
      permethrin at 250 and 500 mg/m2 induced higher mortality and blood feeding
      reduction among susceptible and heterozygous (RS) females as compared to the
      lower concentration (100 mg/m2). The experimental hut trials showed that the best
      personal protection was achieved with the highest permethrin concentration (1,000
      mg/m2). Mosquito genotyping revealed a non-linear relationship in the survival of
      kdr susceptible and resistant genotypes with permethrin dosage. Higher dosages (>
      or =250 mg/m2) killed more efficiently the RS genotypes than did lower dosages
      (50 and 100 mg/m2). CONCLUSION: This study showed that nets treated with high
      permethrin concentrations provided better blood feeding prevention against
      pyrethroid-resistant An. gambiae than did lower concentrations. Permethrin
      treated nets seem unlikely to select for pyrethroid resistance in areas where the
      kdr mutation is rare and present mainly in heterozygous form.

PMID- 15242515
TI  - Association for Immunotherapy of Cancer: Cancer Immunotherapy - 2nd Annual
      Meeting. Mainz, Germany, 6-7 May 2004. Abstracts.

PMID- 15242514
TI  - Analysis of IgG with specificity for variant surface antigens expressed by
      placental Plasmodium falciparum isolates.
AB  - BACKGROUND: Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum
      infected erythrocytes that can sequester in placental intervillous space by
      expressing particular variant surface antigens (VSA) that can mediate adhesion to
      chondroitin sulfate A (CSA) in vitro. IgG antibodies with specificity for the VSA
      expressed by these parasites (VSAPAM) are associated with protection from
      maternal anaemia, prematurity and low birth weight, which is the greatest risk
      factor for death in the first month of life. METHODS: In this study, the
      development of anti-VSAPAM antibodies in a group of 151 women who presented to
      the maternity ward of Albert Schweitzer Hospital in Lambarene, Gabon for delivery
      was analysed using flow cytometry assays. Plasma samples from placenta infected
      primiparous women were also investigated for their capacity to inhibit parasite
      binding to CSA in vitro. RESULTS: In the study cohort, primiparous as well as
      secundiparous women had the greatest risk of infection at delivery as well as
      during pregnancy. Primiparous women with infected placentas at delivery showed
      higher levels of VSAPAM-specific IgG compared to women who had no malaria
      infections at delivery. Placental isolates of Gabonese and Senegalese origin
      tested on plasma samples from Gabon showed parity dependency and gender
      specificity patterns. There was a significant correlation of plasma reactivity as
      measured by flow cytometry between different placental isolates. In the plasma of
      infected primiparous women, VSAPAM-specific IgG measured by flow cytometry could
      be correlated with anti-adhesion antibodies measured by the inhibition of CSA
      binding. CONCLUSION: Recognition of placental parasites shows a parity- and sex-
      dependent pattern, like that previously observed in laboratory strains selected
      to bind to CSA. Placental infections at delivery in primiparous women appear to
      be sufficient to induce functional antibodies which can both recognize the
      surface of the infected erythrocytes as well as block their binding to CSA. The
      correlation between serum reactivities of placental field isolates from different
      geographic locations and collected at different times is indicative of the
      conserved nature of the antigen(s) mediating PAM.

PMID- 15242516
TI  - Pattern of carbon dioxide production and retention is similar in adult pigs when
      fed hourly, but not when fed a single meal.
AB  - BACKGROUND: The understanding of bicarbonate kinetics and CO2 retention in the
      body is necessary to conduct amino acid tracer oxidation studies in both humans
      and laboratory animals. Significant metabolic activity is associated with eating
      which can affect bicarbonate steady state kinetics. A study was conducted to
      assess the impact of feeding regimen on the recovery of labelled bicarbonate and
      energy expenditure in adult female pigs (sows). Five catheterized sows (235 +/- 5
      kg) were fed semi-synthetic diets as: a single meal 2 h into the infusion after
      an overnight fast, or in eight hourly meals starting 2 h before the infusion.
      Oxygen consumption, CO2 production and 14CO2 recovery (ie fraction not retained)
      were determined during primed, constant intravenous infusions of NaH14CO3.
      RESULTS: The 14CO2 recovery (%) after fasting (58.1 +/- 4.8) was lower than that
      after single meal feeding (78.8 +/- 5.9) or hourly meal feeding (81.0 +/- 2.6, P
      = 0.03). CO2 production correlated with 14CO2 recovery during hourly feeding (r =
      0.40, P = 0.01); this relationship was not significant after single meal feeding
      (P = 0.30), probably due to physical activity-associated CO2 production.
      CONCLUSIONS: The correlation of CO2 retention factors with CO2 production during
      hourly feeding suggests that this regimen should be preferred for future amino
      acid kinetics studies.

PMID- 15242518
TI  - Growth cone pathfinding: a competition between deterministic and stochastic
      events.
AB  - BACKGROUND: Growth cone migratory patterns show evidence of both deterministic
      and stochastic search modes. RESULTS: We quantitatively examine how these two
      different migration modes affect the growth cone's pathfinding response, by
      simulating growth cone contact with a repulsive cue and measuring the resultant
      turn angle. We develop a dimensionless number, we call the determinism ratio Psi,
      to define the ratio of deterministic to stochastic influences driving the growth
      cone's migration in response to an external guidance cue. We find that the growth
      cone can exhibit three distinct types of turning behaviors depending on the
      magnitude of Psi. CONCLUSIONS: We conclude, within the context of these in silico
      studies, that only when deterministic and stochastic migration factors are in
      balance (i.e. Psi ~ 1) can the growth cone respond constructively to guidance
      cues.

PMID- 15242519
TI  - Rapid identification and mapping of insertion sequences in Escherichia coli
      genomes using vectorette PCR.
AB  - BACKGROUND: Insertion sequences (IS) are small DNA segments capable of
      transposing within and between prokaryotic genomes, often causing insertional
      mutations and chromosomal rearrangements. Although several methods are available
      for locating ISs in microbial genomes, they are either labor-intensive or
      inefficient. Here, we use vectorette PCR to identify and map the genomic
      positions of the eight insertion sequences (IS1, 2, 3, 4, 5, 30, 150, and 186)
      found in E. coli strain CGSC6300, a close relative of MG1655 whose genome has
      been sequenced. RESULTS: Genomic DNA from strain CGSC6300 was digested with a
      four-base cutter Rsa I and the resulting restriction fragments ligated onto
      vectorette units. Using IS-specific primers directed outward from the extreme
      ends of each IS and a vectorette primer, flanking DNA fragments were amplified
      from all but one of the 37 IS elements identified in the genomic sequence of
      MG1655. Purification and sequencing of the PCR products confirmed that they are
      IS-associated flanking DNA fragments corresponding to the known IS locations in
      the MG1655 genome. Seven additional insertions were found in strain CGSC6300
      indicating that very closely related isolates of the same laboratory strain (the
      K12 isolate) may differ in their IS complement. Two other E. coli K12
      derivatives, TD2 and TD10, were also analyzed by vectorette PCR. They share 36 of
      the MG1655 IS sites as well as having 16 and 18 additional insertions,
      respectively. CONCLUSION: This study shows that vectorette PCR is a swift,
      efficient, reliable method for typing microbial strains and identifying and
      mapping IS insertion sites present in microbial genomes. Unlike Southern
      hybridization and inverse PCR, our approach involves only one genomic digest and
      one ligation step. Vectorette PCR is then used to simultaneously amplify all IS
      elements of a given type, making it a rapid and sensitive means to survey IS
      elements in genomes. The ability to rapidly identify the IS complements of
      microbial genomes should facilitate subtyping closely related pathogens during
      disease outbreaks.

PMID- 15242520
TI  - A multistage theory of age-specific acceleration in human mortality.
AB  - BACKGROUND: Humans die at an increasing rate until late in life, when mortality
      rates level off. The causes of the late-life mortality plateau have been debated
      extensively over the past few years. Here, I examine mortality patterns
      separately for each of the leading causes of death. The different causes of death
      show distinct mortality patterns, providing some clues about the varying
      acceleration of mortality at different ages. RESULTS: I examine mortality
      patterns by first plotting the data of mortality rate versus age on a log-log
      scale. The slope of the age-specific mortality rate at each age is the age
      specific acceleration of mortality. About one-half of total deaths have causes
      with similar shapes for the age-specific acceleration of mortality: a steady rise
      in acceleration from midlife until a well-defined peak at 80 years, followed by a
      nearly linear decline in acceleration. This first group of causes includes heart
      disease, cerebrovascular disease, and accidental deaths. A second group,
      accounting for about one-third of all deaths, follows a different pattern of age
      specific acceleration. These diseases show an approximately linear rise in
      acceleration to a peak at 35-45 years of age, followed by a steep and steady
      decline in acceleration for the remainder of life. This second group includes
      cancer, chronic respiratory diseases, and liver disease. I develop a multistage
      model of disease progression to explain the observed patterns of mortality
      acceleration. CONCLUSIONS: A multistage model of disease progression can explain
      both the early-life increase and late-life decrease in mortality acceleration. An
      early-life rise in acceleration may be caused by increasing rates of transition
      between stages as individuals grow older. The late-life decline in acceleration
      may be caused by progression through earlier stages, leaving only a few stages
      remaining for older individuals.

PMID- 15242521
TI  - APC: the toll road to continued high quality communication.
AB  - In this article we briefly review the reasons and advantages that underly our
      publisher's decision to introduce article-processing charges (APC) for
      manuscripts submitted to Cell Communication and Signaling. The charge is an
      attempt to develop a new business model for distributing biomedical information
      and has been accepted in a number of other journals. APCs will enable BioMed
      Central to continue to provide their excellent service and will help to establish
      our journal.

PMID- 15242523
TI  - Gene transfer of connexin43 into skeletal muscle.
AB  - Cellular cardiomyoplasty using skeletal myoblasts may be beneficial for infarct
      repair. One drawback to skeletal muscle cells is their lack of gap junction
      expression after differentiation, thus preventing electrical coupling to host
      cardiomyocytes. We sought to overexpress the gap junction protein connexin43
      (Cx43) in differentiated skeletal myotubes, using retroviral, adenoviral, and
      plasmid-mediated gene transfer. All strategies resulted in overexpression of Cx43
      in cultured myotubes, but expression of Cx43 from constitutive viral promoters
      caused significant death upon differentiation. Dye transfer studies showed that
      surviving myotubes contained functional gap junctions, however. Retrovirally
      transfected myoblasts did not express Cx43 after grafting into the heart,
      possibly due to promoter silencing. Adenovirally transfected myoblasts expressed
      abundant Cx43 after forming myotubes in cardiac grafts, but grafts showed signs
      of injury at 1 week and had died by 2 weeks. Interestingly, transfection of
      already differentiated myotubes with adenoviral Cx43 was nontoxic, implying a
      window of vulnerability during differentiation. To test this hypothesis, Cx43 was
      expressed from the muscle creatine kinase (MCK) promoter, which is active only
      after myocyte differentiation. The MCK promoter resulted in high levels of Cx43
      expression in differentiated myotubes but did not cause cell death during
      differentiation. MCK-Cx43-transfected myoblasts formed viable cardiac grafts and,
      in some cases, Cx43-expressing myotubes were in close apposition to host
      cardiomyocytes, possibly allowing electrical coupling. Thus, high levels of Cx43
      during skeletal muscle differentiation cause cell death. When, however,
      expression of Cx43 is delayed until after differentiation, using the MCK
      promoter, myotubes are viable and express gap junction proteins after grafting in
      the heart. This strategy may permit electrical coupling of skeletal and cardiac
      muscle for cardiac repair.

PMID- 15242522
TI  - PTTG/securin activates expression of p53 and modulates its function.
AB  - BACKGROUND: Pituitary tumor transforming gene (PTTG) is a novel oncogene that is
      expressed abundantly in most tumors. Overexpression of PTTG induces cellular
      transformation and promotes tumor formation in nude mice. PTTG has been
      implicated in various cellular processes including sister chromatid separation
      during cell division as well as induction of apoptosis through p53-dependent and
      p53-independent mechanisms. The relationship between PTTG and p53 remains
      unclear, however. RESULTS: Here we report the effects of overexpression of PTTG
      on the expression and function of p53. Our results indicate that overexpression
      of PTTG regulates the expression of the p53 gene at both the transcriptional and
      translational levels and that this ability of PTTG to activate the expression of
      p53 gene is dependent upon the p53 status of the cell. Deletion analysis of the
      p53 gene promoter revealed that only a small region of the p53 gene promoter is
      required for its activation by PTTG and further indicated that the activation of
      p53 gene by PTTG is an indirect effect that is mediated through the regulation of
      the expression of c-myc, which then interacts with the p53 gene promoter. Our
      results also indicate that overexpression of PTTG stimulates expression of the
      Bax gene, one of the known downstream targets of p53, and induces apoptosis in a
      human embryonic kidney cell line (HEK293). This stimulation of bax expression by
      PTTG is indirect and is mediated through modulation of p53 gene expression.
      CONCLUSIONS: Overexpression of PTTG activates the expression of p53 and modulates
      its function, with this action of PTTG being mediated through the regulation of c
      myc expression. PTTG also up-regulates the activity of the bax promoter and
      increases the expression of bax through modulation of p53 expression.

PMID- 15242524
TI  - Conditionally replication-competent adenoviral vectors with enhanced infectivity
      for use in gene therapy of melanoma.
AB  - To generate vector Ad.Tyr-E1A, which is cytolytic for tyrosinase-positive
      melanoma cells, we replaced the adenoviral E1A promoter with a human tyrosinase
      enhancer/promoter. To overcome the low transduction efficiency in populations of
      melanoma cells that exhibit a low level of the coxsackievirus-adenovirus receptor
      (CAR), we inserted an RGD-4C peptide into the HI loop of the fiber knob domain of
      the Ad.Tyr-E1A vector. The resulting vector was named Ad.Tyr-E1A(RGD). As a
      result of these changes, the transduction efficiency of the RGD-modified vector
      was increased both in vitro and in vivo. Western blot analysis proved that
      infection of cells with the Ad.Tyr-E1A(RGD) vector led to expression of the E1A
      gene selectively in tyrosinase-positive melanoma cell lines, but not in
      tyrosinase-negative cell lines. The Ad.Tyr-E1A(RGD) vector was as potent in its
      cytotoxic effect as a tumor nonselective vector (Ad.CMV-E1A) in tyrosinase
      positive melanoma cell lines. The Ad.Tyr-E1A(RGD) vector produced a higher vector
      particle yield in tumor cells than did the Ad.Tyr-E1A vector. Intratumoral
      injection of the Ad.Tyr-E1A(RGD) vector into xenotransplanted human melanoma
      tumors led to tumor regression in vivo. The combination of tumor-specific
      replication and enhanced infectivity generates a more potent CRAD vector for gene
      therapy of melanoma.

PMID- 15242525
TI  - Enhanced transgene expression in quiescent and activated human CD8+ T cells.
AB  - The level of expression of retroviral vector-encoded proteins in T cells,
      decreasing during periods of quiescence, could be an obstacle to their clinical
      utility. To identify promoter systems that could increase the strength and
      persistence of transgene expression in primary human CD8(+) T cells, we designed
      a panel of Moloney retroviral vectors to express a destabilized enhanced green
      fluorescent protein (d4EGFP) reporter protein (t(1/2) = 4 hr). We found that the
      promoters phosphoglycerate kinase (Pgk), beta-actin, and long terminal repeat
      (LTR) produced the highest levels of d4EGFP expression in proliferating T cells,
      but that expression dramatically declined in quiescent cells with all promoters.
      To improve gene expression, we examined the effect of the beta-interferon (IFN)
      scaffold attachment region (SAR). This SAR augmented expression from mammalian
      promoters in cycling T cells, but had a small effect on maintenance of expression
      in resting T cells. However, when the SAR was combined with the LTR promoter, it
      significantly enhanced expression in resting and cycling cells. These data
      support use of the IFN-beta SAR with the LTR in Moloney retroviral vectors to
      help sustain gene expression in resting primary human CD8(+) T cells and to
      enhance gene expression in activated T cells.

PMID- 15242526
TI  - Osteoinduction by bone morphogenetic protein 2-expressing adenoviral vector:
      application of biomaterial to mask the host immune response.
AB  - We constructed a human bone morphogenetic protein 2 (BMP-2)-expressing adenoviral
      vector, AxCABMP-2, which showed osteoinduction in immunosuppressed rats. In
      immunocompetent rats, new bone was not induced, because of the rapid elimination
      of transduced cells. Biomaterials such as collagen can be used as carriers for
      the delivery of DNA vectors, allowing prolonged expression of plasmid DNA in
      normal animals. We evaluated osteoinduction with AxCABMP-2 and atelopeptide type
      I collagen in immunocompetent rats. Collagen plus AxCABMP-2 (BMP group), collagen
      plus AxCALacZ (LacZ group), or collagen alone (CL group) was implanted into calf
      muscle pouches in immunocompetent rats, or AxCABMP-2 alone (injection group) was
      injected into the calf muscle. On days 3, 7, 14, and 21 after treatment,
      osteoinduction was evaluated. In the BMP group, bone formation was not observed
      on days 3 and 7. On day 14, radiographic formation was seen, but little bone
      formation was detected histologically. On day 21, new bone formation was observed
      both radiologically and histologically. In the other groups, osteoinduction was
      not found at any time. Immunohistochemical analysis on days 3 and 7 revealed
      decreased immunogenicity in the BMP group compared with the injection group.
      These findings suggested that collagen was an effective masking material for our
      vector.

PMID- 15242527
TI  - Survival of encapsulated human primary fibroblasts and erythropoietin expression
      under xenogeneic conditions.
AB  - Allogeneic cells are the most attractive source for cell transplantation, as the
      use of xenogeneic cells is hampered by safety concerns and the use of autologous
      cells involves practical difficulties. The immune rejection of allogeneic cells
      can be overcome by physical immunoprotection provided by polymer encapsulation.
      To study the variability of cell and donor sources, we compared different primary
      human cells as candidates for gene therapy-mediated delivery of human
      erythropoietin (hEpo). DARC-3.1 fibroblasts, MDX-01 fibroblasts, and ARPE-19
      retinal pigment epithelial cells were encapsulated into polyethersulfone hollow
      fibers and implanted for 1 month in nude mice as well as in immunocompetent and
      FK506-immunosuppressed mice to test their in vivo resistance, with the assumption
      that xenogeneic conditions constitute a stringent model for human application.
      DARC-3.1 fibroblasts showed the best survival, prompting us to evaluate cell
      lineages from the same donor (DARC-3.2) or another donor (DARC-4.3 and DARC-4.4).
      With the exception of DARC-4.3, the remaining three lineages showed comparable
      survival in immunocompetent C3H and DBA/2J mice. DARC-3.1 fibroblasts were
      retrovirally engineered with hEpo cDNA, reaching a secretion level of 170 IU of
      hEpo per 10(6) cells per day. Encapsulated DARC-3.1-hEpo cells led to
      significantly increased hematocrits in the various hosts and under various
      transplantation conditions. The present study shows that encapsulated primary
      human DARC-3.1 fibroblasts are able to survive under xenogeneic conditions and,
      once engineered with hEpo cDNA, to increase the hematocrit of transplanted mice.

PMID- 15242528
TI  - Novel bidirectional vector strategy for amplification of therapeutic and reporter
      gene expression.
AB  - Molecular imaging methods have previously been employed to image tissue-specific
      reporter gene expression by a two-step transcriptional amplification (TSTA)
      strategy. We have now developed a new bidirectional vector system, based on the
      TSTA strategy, that can simultaneously amplify expression for both a target gene
      and a reporter gene, using a relatively weak promoter. We used the synthetic
      Renilla luciferase (hrl) and firefly luciferase (fl) reporter genes to validate
      the system in cell cultures and in living mice. When mammalian cells were
      transiently cotransfected with the GAL4-responsive bidirectional reporter vector
      and various doses of the activator plasmid encoding the GAL4-VP16 fusion protein,
      pSV40-GAL4-VP16, a high correlation (r(2) = 0.95) was observed between the
      expression levels of both reporter genes. Good correlations (r(2) = 0.82 and
      0.66, respectively) were also observed in vivo when the transiently transfected
      cells were implanted subcutaneously in mice or when the two plasmids were
      delivered by hydrodynamic injection and imaged. This work establishes a novel
      bidirectional vector approach utilizing the TSTA strategy for both target and
      reporter gene amplification. This validated approach should prove useful for the
      development of novel gene therapy vectors, as well as for transgenic models,
      allowing noninvasive imaging for indirect monitoring and amplification of target
      gene expression.

PMID- 15242529
TI  - Interleukin 13 gene transfer in liver ischemia and reperfusion injury: role of
      Stat6 and TLR4 pathways in cytoprotection.
AB  - Ischemia and reperfusion injury (IRI) represents the major problem in clinical
      liver transplantation. We have shown that transcription of signal transducer and
      activator of transcription 4 (Stat4) plays a key role in the mechanism of hepatic
      IRI, whereas local induction of interleukin 13 (IL-13) is cytoprotective. The
      disruption of innate Toll-like receptor 4 (TLR4) signaling prevents mouse livers
      from undergoing fulminant IRI. This study analyzes in vivo interplay between
      innate (TLR4) and adaptive (Stat6) immunity in Ad-IL-13 (recombinant adenovirus
      encoding IL-13) cytoprotection in hepatic IRI. Using a partial 90-min lobar warm
      ischemia model, groups of wild-type and Stat6-deficient knockout mice were
      assessed for the severity of hepatocellular damage at 6 hr postreperfusion.
      Unlike in wild-type mice, treatment of Stat6 knockout recipients with Ad-IL-13
      failed to improve hepatic function/histology. The expression of mRNAs encoding
      tumor necrosis factor alpha/IL-1 beta and IL-2/interferon gamma remained
      depressed in the wild-type plus Ad-IL-13 group, but not in the Stat6 knockout
      plus Ad-IL-13 group. Ad-IL-13 increased antioxidant heme oxygenase 1 (HO-1)
      expression and prevented TLR4 activation in livers of Stat6-competent (wild-type)
      mice. In contrast, low HO-1 expression and enhanced TLR4 expression were recorded
      in Stat6 knockout recipients despite Ad-IL-13 therapy. Thus (1) Stat6 is required
      for Ad-IL-13 to prevent IRI, and (2) depression of TLR4 activation is Stat6
      dependent. In conclusion, the Stat6 pathway operates as a key negative regulator
      in the hepatic inflammatory ischemia-reperfusion response. This study outlines
      requirements for Ad-IL-13 use to maximize the organ donor pool through the use of
      liver transplants despite prolonged ischemia.

PMID- 15242530
TI  - Immunotherapy of cancer using systemically delivered gene-modified human T
      lymphocytes.
AB  - The use of gene-engineered T cells expressing chimeric single-chain (scFv)
      receptors capable of codelivering CD28 costimulation and T cell receptor zeta
      chain (TCR-zeta) activation signals has emerged as a promising treatment regimen
      for cancer. Using retroviral transduction, primary human T lymphocytes were gene
      engineered to express the scFv-CD28-zeta chimeric receptor reactive with the
      ErbB2 tumor-associated antigen. We demonstrated the ability of these gene
      engineered human T cells to produce high levels of cytokines, proliferate
      vigorously, and mediate lysis of ErbB2(+) tumors in an antigen-specific manner.
      Furthermore, such gene-engineered human T cells significantly delayed the growth
      of two distinct subcutaneous ErbB2(+) human tumors in irradiated nonobese
      diabetic-severe combined immunodeficient (NOD-SCID) mice after systemic
      administration. These preclinical studies are an important proof of principle
      that human T cells may be genetically redirected to tumors in cancer patients.

PMID- 15242531
TI  - Immune responses to recombinant adeno-associated virus vectors: putting
      preclinical findings into perspective.

PMID- 15242532
TI  - Incidence and risk factors for sexually transmitted infections among women in an
      Alabama HIV clinic.
AB  - The objectives of this study were to assess the prevalence and incidence of
      curable sexually transmitted infections (STI), i.e., gonorrhea, chlamydial
      infection, or trichomoniasis, in a cohort of HIV-infected women. The study
      population was derived from women seeking primary care at an outpatient
      university HIV clinic who were participants in a women's natural history study.
      Enrollees (n = 225) were predominantly African-American, heterosexually infected,
      with mean age 35 years. Mean entry CD4+ T cell count was 405 cells/mm3. Over 6%
      were STI positive at initial screening. Subsequently, the combined curable STI
      incidence was 4.82/1000 woman-months over a median of 33 months of observation.
      Of 36 incident STIs, trichomoniasis was most common (n = 32). Predictors for
      acquisition of a curable STI included absenteeism at scheduled clinic
      appointments, RR = 1.99 (1.28, 3.08), and a higher CD4+ T cell count, RR = 1.15
      (1.0028, 1.3115) for 100 cells. Interventions to prevent curable STI in HIV
      infected women are warranted in primary care settings.

PMID- 15242533
TI  - Reduced value of thallium-201 single-photon emission computed tomography in the
      management of HIV-related focal brain lesions in the era of highly active
      antiretroviral therapy.
AB  - To evaluate the diagnostic value of thallium-201 single-photon emission computed
      tomography (201Tl SPECT) in the management of focal brain disorders in the era of
      highly active antiretroviral therapy (HAART), a validation study of diagnostic
      procedure was performed in a tertiary clinical care center in Italy. Thirty-eight
      consecutive HIV-infected patients with neurological impairment and focal brain
      lesions (FBL) were enrolled in a prospective evaluation and underwent diagnostic
      procedures according to a standardized protocol based on modified previously
      released guidelines. Six out of seven PCNSL presented high uptake at 201Tl SPECT
      [sensitivity 86% (95% CI 42-99); specificity 77% (95% CI 58-90); positive
      predictive value (PPV) 46% (95% CI 20-74); negative predictive value (NPV) 96%
      (95% CI 78-100)]. Among toxoplasmic encephalitis (TE) cases 14 showed no uptake
      and 5 showed an increased uptake [sensitivity 74% (95% CI 49-90); specificity 42%
      (95% CI 21-66); PPV 56% (95% CI 35-75); NPV 61% (95% CI 32-85)]. Patients taking
      HAART were more likely to display an increased uptake of 201Tl in the cerebral
      lesions than patients without HAART (OR 5.07; 95% CI 1.19-21.5). Considering only
      the patients with diagnosis of TE, 60% of patients who showed high radionuclide
      uptake were taking HAART, while 79% of patients without relevant uptake were not
      taking HAART. As a result of the impact of HAART, the diagnostic value of 201Tl
      SPECT in the management of HIV-associated FBL could be substantially reduced.
      This observation suggests that in HAART-treated patients, this diagnostic tool be
      used only when combined with other more specific diagnostic markers.

PMID- 15242534
TI  - Evaluation of the virological and metabolic effects of switching protease
      inhibitor combination antiretroviral therapy to nevirapine-based therapy for the
      treatment of HIV infection.
AB  - In spite of indisputable benefits, the use of antiretroviral therapy is
      associated with multiple metabolic complications. Switching to simpler regimens
      might maintain viral suppression, improve metabolic side effects, and provide
      insight into the pathogenesis of these complications. Our objective was to
      carefully characterize the virological and metabolic effects of switching from a
      successful protease inhibitor (PI)-based antiretroviral regimen to a
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with
      nevirapine (NVP). Forty patients, taking their first successful (less than 40 HIV
      RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not
      tolerate NVP, substitution with efavirenz was allowed. The duration of the study
      was 48 weeks. At 12 weeks intervals subjects had multiple virological and
      metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin,
      blood lipids, and lipoproteins. A subgroup of 18 patients also had body
      composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as
      well as insulin tolerance tests. Ninety-five percent of the patients maintained
      viral suppression (95% CI 88-100%); only one patient failed and another developed
      hepatitis. There were improvements in glucose (decreased fasting glucose,
      insulin, and improved insulin tolerance) and lipid metabolism (decreased
      triglycerides and increased HDL), but no changes in body composition and bone
      mineral density. Our study supports a pathogenic role for PIs in the development
      of hypertriglyceridemia and insulin resistance, but a more limited role in the
      fat redistribution syndrome.

PMID- 15242535
TI  - Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks
      after single-dose nvp prophylaxis: HIVNET 012.
AB  - We compared nevirapine (NVP) resistance (NVPR) mutations in maternal plasma 7
      days vs. 6-8 weeks after single-dose NVP prophylaxis. In the HIVNET 012 trial,
      Ugandan women received a single dose of NVP in labor for prevention of HIV-1
      mother-to-child transmission. NVPR mutations were detected in 70 (25%) of 279
      women 6-8 weeks after NVP. Samples collected 7 days after NVP were analyzed from
      a subset of those 279 women. Genotyping was performed with the ViroSeq HIV-1
      Genotyping System. NVPR was analyzed using paired samples from 7 days and 6-8
      weeks after NVP. Sixty-five women had genotyping results obtained for samples
      collected at both 7 days and 6-8 weeks post-NVP. Twenty-one (32%) of those women
      had NVPR mutations detected in one or both samples. This included three women
      with NVPR at 7 days only, seven with NVPR at 6-8 weeks only, and 11 with NVPR at
      both time points. Eight women had >1 NVPR mutation detected 7 days after NVP.
      Y181C was the most common NVPR mutation detected at 7 days, whereas K103N was the
      most common NVPR mutation detected at 6-8 weeks. We conclude that NVPR may be
      detected in women as early as 7 days after single-dose NVP. Complex patterns of
      NVPR are detected in some women. The Y181C NVPR mutation often fades from
      detection by 6-8 weeks. In contrast, the K103N mutation emerges more slowly, but
      often remains detectable 6-8 weeks after NVP.

PMID- 15242536
TI  - gp340 (SAG) binds to the V3 sequence of gp120 important for chemokine receptor
      interaction.
AB  - Human saliva contains multiple components that inhibit HIV-1 infection in vitro,
      which may contribute to low oral HIV-1 transmission. Salivary agglutinin (SAG) is
      a high-molecular-weight glycoprotein encoded by DMBT-1 and identical to gp340, a
      member of the lung scavange receptor, cysteine-rich receptor family. gp340 binds
      to surfactants A and D, which is believed to function in the clearance of
      microorganisms from the lung, as part of the innate immune response. Previously
      we reported that SAG (gp340) specifically inhibits HIV-1 infection with broad
      activity against diverse HIV-1 isolates. This gp340 inhibitory activity is
      mediated by binding to viral gp120 and involves a region different from the CD4
      binding site on gp120. Here, we report that the gp340-binding region is localized
      to a linear, highly conserved sequence near the stem of the V3 loop that is
      critical for chemokine receptor interaction during viral binding and infection.
      The interaction of gp340 with gp120 is enhanced by prebinding of sCD4 to gp120,
      suggesting that gp340 inhibitory activity is mediated by blocking access of the
      gp120 to the chemokine receptor.

PMID- 15242537
TI  - AZT enhances osteoclastogenesis and bone loss.
AB  - A variety of metabolic complications have been reported to be associated with
      highly active antiretroviral therapy (HAART), including osteopenia and
      osteoporosis. In this study, we determine the effects of zidovudine (AZT), a
      nucleoside reverse transcriptase inhibitor, on osteoclastogenesis in a cultured
      mouse macrophage preosteoclast cell line (RAW264.7), in mouse primary bone marrow
      macrophage-monocyte precursors, and on bone mineral density in mice. The results
      indicate that AZT induces an increase in osteoclastogenesis in the mouse
      preosteoclast cell line and in mouse bone marrow osteoclast precursors in the
      presence of RANKL. This increased osteoclastogenesis is dependent upon the
      concentration of AZT. AZT increases the promoter activity of tartrate-resistant
      acid phosphatase (TRAP) and the binding and function of the nuclear transcription
      protein, NF-kappaB, in RAW264.7 cells. Therefore, the effect of AZT is mediated,
      at least in part, by enhancing RANKL-mediated osteoclastogenesis. Bone mineral
      density (BMD) in AZT-treated mice is decreased and histopathology shows marked
      osteopenia. These results support an important role of AZT-stimulated
      osteoclastogenesis in HAART-induced osteopenia.

PMID- 15242538
TI  - Increased frequency of CD27- (naive) B cells and their phenotypic alteration in
      HIV type 1-infected patients.
AB  - To investigate HIV-1-related B cell disorders, the quantity of peripheral CD27
      negative (CD27-) B cells, their CD38, CD95, and bcl-2 intensities, and their
      apoptosis susceptibility were examined by flow cytometry analysis in 16 drug
      naive patients, 27 HAART-treated patients, and 20 uninfected controls. CD27- B
      cells have been recognized as naive B cells. The mean percentage of CD27- B cells
      was significantly higher in drugnaive patients (88.1%) and in HAART-treated
      patients (83.9%) than in controls (68.6%) (p < 0.01). The intensities of CD38 and
      CD95 on CD27- B cells were significantly higher in drug-naive patients than in
      controls (p < 0.01). The intensity of CD95 on CD27- B cells in HAART-treated
      patients was lower than that of drug-naive patients, but significantly higher
      than that of controls (p < 0.01). The intensity of bcl-2 on CD27- B cells in drug
      naive patients was lower than that of controls. In drug-naive patients, CD27-B
      cells with high CD38 expression represented low bcl-2 expression. The CD27- B
      cells of drug-naive patients showed an increased susceptibility to apoptosis,
      characterized by diminished cell size and a high frequency of annexin-V binding,
      compared with controls and HAART-treated patients. These findings suggested that
      HIV-1 infection affects peripheral CD27- (naive) B cells as well as CD27+
      (memory) B cells and that CD27- B cells might be activated and rendered highly
      susceptible to apoptosis by HIV-1 infection. Some phenotypic alterations in CD27-
      B cells may continue after the reduction of HIV-1 loads by effective antiviral
      therapy.

PMID- 15242539
TI  - CCR5 receptor expression is down-regulated in HIV type 2 infection: implication
      for viral control and protection.
AB  - HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to
      disease and decreased rate of transmission. Observational studies in Senegal have
      demonstrated protection from HIV-1 infection, although the putative mechanism for
      immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a
      cohort of commercial sex workers in Dakar, Senegal and identified individuals
      with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up
      regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5
      was not correlated with activation markers (HLA-DR), beta-chemokine levels, or
      plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell
      activity as measured by intracellular cytokine production. We postulate that down
      regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease
      course and to the protective mechanism against HIV-1 superinfection, mediated in
      part by HIV-2-specific cellular immune responses.

PMID- 15242540
TI  - Lymphocyte homeostasis in HIV-infected northern Thais.
AB  - Cross-sectional laboratory data were used to model the patterns of total
      lymphocyte count and lymphocyte subpopulation counts among persons with chronic
      HIV-1 subtype E (CRF01_AE) infection during the 6.5 years preceding death. The
      data cover 331 HIV-infected decedents from a heterosexual HIV transmission study
      of 590 northern Thai couples enrolled in 1992-1998. From blood collected at
      enrollment, the lymphocyte phenotypes (CD3, CD8, CD4, natural killer, and B
      cells) were stained using two-color monoclonal antibody combinations and
      quantified by flow cytometry. Piecewise linear splines modeled the associations
      between lymphocyte levels and time before death. Mean CD3, CD8, and B cell levels
      showed no temporal associations from 6.5 to 2 years before death, but each
      declined significantly during the 2 years before death. CD3 levels declined 31.0%
      [95% confidence interval (-40.3%, -19.8%)] and CD8 levels declined 24.6% (-35.4%,
      -13.5%) annually in the 2 years prior to death. In contrast, CD4 and NK cell
      levels declined little from 6.5 to 4.5 years before death but declined
      significantly over the 4.5 years prior to death. CD4 levels declined 22.1% (
      29.2%, -12.0%) annually from 4.5 to 2 years prior to death and 63.7% (-72.3%, 
      53.6%) annually over the remaining 2 years. Similar lymphocyte patterns have been
      reported in U. S. and European populations with HIV-1 subtype B infection.

PMID- 15242541
TI  - Enhanced sensitivity of detection of cytotoxic T lymphocyte responses to HIV type
      1 proteins using an extended in vitro stimulation period for measuring effector
      function in volunteers enrolled in an ALVAC-HIV phase I/II prime boost vaccine
      trial in Thailand.
AB  - A phase I/II prime-boost vaccine trial in HIV-1-seronegative adults was conducted
      in Thailand using ALVAC-HIV (vCP1521) as a prime, boosting with either oligomeric
      gp160 TH023/LAI or Chiron HIV Thai subtype E (CM235) plus U. S. subtype B (SF2)
      gp120. Cytotoxic T lymphocyte (CTL) assays were conducted at one of the vaccine
      trial sites (Siriraj Hospital) at a single time point following the completion of
      immunization demonstrated that 8 of 50 (16%) vaccine recipients showed HIV
      specific CTL by standard chromium release assay (CRA) after in vitro stimulation
      (IVS) for 2 weeks. Five additional vaccinees (13/50 = 26%) showed CTL responses
      after IVS for up to 4 weeks. Moreover, one volunteer with a positive CTL response
      to a single HIV antigen at Day 14 demonstrated a response to an additional HIV-1
      antigen(s) after the longer IVS period. CTL activity was CD8+ restricted. Despite
      extension of the IVS up to 4 weeks, no CTL responses were detected in placebo
      recipients. These results imply that extension of the IVS period may increase the
      sensitivity of the CRA when measuring HIV-specific CTL in ALVAC-HIV prime-boost
      recipients without compromising specificity.

PMID- 15242542
TI  - Multiprotein HIV type 1 clade B DNA and MVA vaccines: construction, expression,
      and immunogenicity in rodents of the MVA component.
AB  - Recombinant modified vaccinia virus Ankara (MVA) expressing SIV or SHIV Gag-Pol
      and Env, alone or in conjunction with a related DNA vaccine, effectively controls
      immunodeficiency virus infections in nonhuman primates. Here we describe the
      construction, characterization, and immunogenicity of MVA/HIV 48, a candidate HIV
      1 clade B Gag-Pol-Env vaccine. A novel transfer vector was designed to allow the
      incorporation of HIV genes regulated by vaccinia virus promoters together with a
      reporter gene into a single site in the MVA genome and to automatically delete
      the reporter after the initial isolation of the recombinant MVA. MVA/HIV 48
      contains chimeric HIV-1 HXB-2/BH10 gag-pol sequences, a deletion of integrase,
      inactivating point mutations in reverse transcriptase, and HIV-1 ADA env
      sequences with a truncation of most of the cytoplasmic domain to enhance
      expression on the plasma membrane. Cells infected with MVA/HIV 48 expressed HIV
      proteins, which were processed to the expected size. The Env was inserted into
      the plasma membrane and was functional in a CCR5 coreceptor-dependent cell fusion
      assay. Moreover, virus-like particles were released into the medium and budding
      particles containing Env were visualized by immunoelectron microscopy. Rodents
      that were immunized with MVA/HIV 48 produced antibodies, which neutralized a
      heterologous HIV-MN strain, and Gag-specific CD8 T cells. In the accompanying
      paper, we show that MVA/HIV 48 provided efficient boosting of an HIV DNA vaccine.

PMID- 15242543
TI  - Multiprotein HIV type 1 clade B DNA/MVA vaccine: construction, safety, and
      immunogenicity in Macaques.
AB  - Recently, a simian/human immunodeficiency virus (SHIV) vaccine consisting of
      priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env
      expressing recombinant modified vaccinia Ankara (rMVA) has successfully
      controlled a virulent SHIV challenge in a macaque model. In this, and the
      accompanying paper, we report on the construction and testing of a Gag-Pol-Env
      DNA/MVA vaccine for HIV-1/AIDS. The DNA vaccine, pGA2/JS2, expresses aggregates
      of Gag proteins and includes safety mutations that render it integration, reverse
      transcription, and packaging defective. The rMVA vaccine, MVA/HIV 48, is
      integration and reverse transcription defective and has a truncated Env to
      enhance expression on the plasma membrane. In a study in rhesus macaques, priming
      with pGA2/JS2 and boosting with MVA/HIV 48 raised high frequencies of T cells for
      Gag and Env and lower frequencies of T cells for PR, RT, and Tat. Stimulations
      with five peptide pools for Gag and seven peptide pools for Env revealed epitopes
      for cellular immune responses throughout Gag and Env. On average, CD4 T cells
      from the vaccinated animals recognized 7.1 peptide pools and CD8 T cells, 3.2
      peptide pools. Both the height and the breadth of the elicited cellular response
      provide hope that this multiprotein DNA/MVA vaccine will successfully control
      clade B isolates of HIV-1, as well as contribute to the control of other clades
      and recombinant forms of HIV-1/AIDS.

PMID- 15242544
TI  - Identification of a highly divergent HIV type 2 and proposal for a change in HIV
      type 2 classification.
AB  - We report the complete genome sequence of a highly divergent strain of human
      immunodeficiency virus type 2 (HIV-2), 96FR12034, identified in France from a
      patient of West African origin. This lineage, H, represents only the third
      definitive instance of a monkey-to-human transfer of SIVsm that has given rise to
      pathogenic HIV-2. As the different "subtypes" of HIV-2 are analogous to the
      different groups of HIV-1 we propose that HIV-2 subtypes henceforth by renamed
      groups in agreement with the HIV Nomenclature Committee. The single-strain
      lineages C to G and the 96FR12034 lineage identified here should be considered
      only as putative groups until related strains are identified that confirm
      circulation of these viruses in the human population.

PMID- 15242545
TI  - V118I substitution in the reverse transcriptase gene of HIV type 1 CRF02_AG
      strains infecting drug-naive individuals in Cameroon.
AB  - We describe the resistance-associated substitutions that are present in the
      reverse transcriptase (RT) genes of HIV-1 CRF02_AG strains infecting drug-naive
      villagers of Cameroon. The 11 sequences analyzed were previously subtyped as
      CRF02_AG in the gag, pro, and env genes, and this work revealed that most (10/11)
      had a concordant subtype (CRF02_AG) in the pol gene, while one sequence had
      discordant subtype (A1) in the pol gene. Classification of the CRF02_AG sequences
      was further confirmed by recombination breakpoint analysis, which revealed a
      mosaic composition similar to the reference strain IbNG. Analysis of the RT genes
      for resistance-associated substitutions revealed two sequences containing a V118I
      substitution. Even though no other resistance-associated substitutions were
      found, the presence of V118I, which is implicated in resistance to reverse
      transcriptase inhibitors, in CRF02_AG strains infecting drug-naive individuals
      should be considered when introducing these antiretrovirals in areas where
      CRF02_AG is the predominant subtype, such as Cameroon.

PMID- 15242546
TI  - A New STLV-1 in a household pet Cercopithecus nictitans from Gabon.
AB  - A recent serological survey of wild-born captive monkeys from Gabon, Central
      Africa, revealed that 1 of 20 Cercopithecus nictitans tested was infected with a
      new simian T cell lymphotropic virus type 1 (STLV-1). We investigated the
      molecular relationship between the STLV-1 strain present in this C. nictitans
      (CN01) and the other available HTLV/STLV strains. Phylogenetic analysis of the
      env (gp46 and gp21) region showed that the new STLV(nict) clusters with the HTLV
      1/STLV-1 group and not with the other nictitans STLVs belonging to the STLV-3
      group. Moreover, our new STLV(nict) is closely related to the molecular subtype
      D, which presently includes five HTLV-1 and three mandrill STLV-1 strains from
      Gabon and two from Cameroon. These data show that C. nictitans may be the natural
      carrier of two different molecular types of STLV, one related to STLV-3 and the
      other possibly one of the simian STLV type 1 counterparts of HTLV-1 subtype D.

PMID- 15242547
TI  - Compartmentalization of drug resistance-associated mutations in a treatment-naive
      HIV-infected female.
AB  - Development of a drug-resistant variant of HIV-1 has been one of the major
      concerns contributing to the transmission of the virus. A 40-year-old woman
      presented to the clinic with micosis and oral candidiasis. The subject was
      referred for HIV-1 diagnosis. Subsequent investigations revealed a very low CD4 T
      cell count (48 cell/microl blood) and high plasma HIV-1 RNA load (4.33 x 10(5)
      copy/ml). A 1.3-kb pol fragment was sequenced in virus collected from plasma and
      the vaginal compartment. Plasma virus had no mutation in reverse transcriptase
      and one mutation in protease (L63P). On the other hand vaginal virus contained
      L63P and M184V mutations in protease and reverse transcriptase, respectively.
      These mutations were accompanied by several other mutations in previously
      identified CTL epitopic regions of the two genes. In the absence of
      antiretroviral treatment, a drug-resistant mutant was thought to develop because
      of immune pressure. This is the first report describing the role of immune
      pressure in the development of a drug-resistant virus.

PMID- 15242548
TI  - Redox control of blood coagulation.

PMID- 15242549
TI  - Functional role of NADPH oxidase in activation of platelets.
AB  - Involvement of phagocyte NADPH oxidase in host defense response is well
      established. In contrast, little is known about the functional role of NADPH
      oxidase in platelets. In this study, we analyzed involvement of platelet NADPH
      oxidase in aggregation of human platelets and in amplification of production of
      reactive oxygen species (ROS) by activated human neutrophils. Apocynin, a known
      NADPH oxidase inhibitor, as well as superoxide dismutase mimetic
      Mn(III)tetrakis(1-methyl-1-pyridyl)porphyrin, inhibited ROS generation by
      collagen-activated platelets, collagen-induced aggregation of platelets, as well
      as collagen-induced release of thromboxane B2. These data suggest the key role of
      intracellular ROS derived from NADPH oxidase in the control of thromboxane A2
      (TXA2) production in platelets stimulated by collagen. Apocynin also inhibited
      thrombin-induced ROS production and thrombin-induced platelet aggregation.
      Activation of neutrophils with latex resulted in an outburst of ROS that was
      inhibited by apocynin. ROS production by latex-stimulated platelets was modest
      and also inhibited by apocynin. However, when a mixture of platelets and
      neutrophils was stimulated with latex, ROS production was three to six times
      higher in comparison with activation of neutrophils alone. Platelet-dependent
      augmentation of neutrophil ROS production was abrogated by TXA2 synthase
      inhibitor (furegrelate, 1 microM) or by aspirin (300 microM). In summary, NADPH
      oxidase in platelets seems to play a major role as an intracellular signaling
      mechanism in the activation of platelets. However, in host defense response
      involving neutrophils and platelets, platelets enhance ROS production by
      neutrophils and possibly their cytotoxic potential via the release of TXA2, which
      in turn in platelets is not affected by the extracellular release of free
      radicals.

PMID- 15242550
TI  - Superoxide-related signaling cascade mediates nuclear factor-kappaB activation in
      acute inflammation.
AB  - The nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a
      pivotal role in the induction of genes involved in physiological processes, as
      well as in the response to inflammation. In this study, we used a selective
      nonpeptidyl superoxide dismutase mimetic, M40403, to investigate the role of
      superoxide anion in NF-kappaB activation during acute inflammation in mice.
      Injection of carrageenan into the pleural cavity of mice induced an acute
      inflammatory response characterized by fluid accumulation in the pleural cavity
      that contained a large number of neutrophils, as well as an increased production
      of tumor necrosis factor-alpha and interleukin-1beta. All parameters of
      inflammation were attenuated by M40403 (10 mg/kg i. p., 30 min prior to
      carrageenan administration). These inflammatory events were associated with the
      activation of NF-kappaB in the lung. In particular, the appearance of inhibitory
      protein kappaB-alpha (IkappaB-alpha) in homogenates of lung tissues was
      investigated by immunoblot analysis at 4 h after carrageenan administration.
      IkappaB-alpha levels were substantially reduced in the lung tissue from
      carrageenan-treated mice in comparison with sham-treated mice. Furthermore, to
      detect NF-kappaB/DNA binding activity, whole extracts from lung tissue of each
      mouse were analyzed by electrophoretic mobility-shift assay. The DNA binding
      activity significantly increased in whole extracts obtained from lung tissues of
      vehicle-treated mice 4 h after carrageenan administration. Treatment of mice with
      M40403 caused a significant inhibition of carrageenan-induced IkappaB-alpha
      degradation and NF-kappaB/DNA binding activity. These data confirm that M40403
      exerts a potent antiinflammatory activity and clearly demonstrate that the
      reduction of the inflammatory process is associated with modification of the
      activation of signal transduction pathways.

PMID- 15242551
TI  - Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of
      tissue factor pathway inhibitor through association with its carboxy-terminal
      region.
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that
      inhibits the initial reactions of blood coagulation. In this study, we explored
      the nature of active components that reduce the anticoagulant activity of TFPI in
      oxidized low-density lipoprotein (ox-LDL). The organic solvent-soluble fraction
      obtained from ox-LDL was fractionated by normal-phase HPLC. The binding profile
      of each fraction to TFPI showed a single peak eluting near purified oxidized
      phospholipid. To explore further the components in oxidized phospholipid that
      inhibit TFPI activity, we used oxidized phospholipids that mimic the biological
      activity of ox-LDL. The oxidation products of 1- and/or 2-oleoyl
      phosphatidylcholine or phosphatidylethanolamine were the most potent inhibitors
      of TFPI activity, whereas those of arachidonyl phosphatidylcholine possessed only
      a weak inhibitory effect on the TFPI activity. These oxidized phospholipids
      mainly associated with the C-terminal basic region of the TFPI molecule. The
      results indicate that oxidation products of delta-9 unsaturated phospholipids are
      candidate active components of ox-LDL that impair the function of TFPI through
      specific association with its C-terminal basic region.

PMID- 15242552
TI  - Rac regulates thrombin-induced tissue factor expression in pulmonary artery
      smooth muscle cells involving the nuclear factor-kappaB pathway.
AB  - Pulmonary hypertension is associated with enhanced thrombogenicity of the vessel
      wall contributing to vascular remodeling. However, the signaling mechanisms
      promoting this prothrombotic state are not resolved. Here we investigated the
      role of the GTPase Rac in the regulation of tissue factor (TF) expression and
      activity in response to thrombin in pulmonary artery smooth muscle cells (PASMC).
      TF mRNA and protein expression and surface procoagulant activity were increased
      by thrombin in PASMC. These responses were enhanced in the presence of the
      constitutively active Rac mutant RacG12V, but were abrogated in cells expressing
      dominant-negative RacT17N. Thrombin and RacG12V also increased human TF promoter
      activity primarily involving a sequence between -636 and -111 bp containing a
      distal, nuclear factor-kappaB (NFkappaB)-dependent enhancer element. Indeed,
      thrombin and RacG12V stimulated NFkappaB-dependent transcriptional activity, and
      overexpression of p50/p65 significantly increased human TF promoter activity.
      Moreover, in RacG12V-overexpressing cells, TF promoter activity was significantly
      decreased by coexpression of dominant-negative mutants of IkappaBalpha and
      IkappaBKalpha, which prevent NFkappaB activation. As enhanced NFkappaB activity
      has been observed in patients with pulmonary hypertension, Rac-dependent
      activation of the NFkappaB pathway may be a critical element promoting thrombin
      induced TF expression and activity, and thus a prothrombotic state in pulmonary
      hypertension.

PMID- 15242553
TI  - Enhanced plasminogen activator inhibitor-1 expression in transgenic mice with
      hepatocyte-specific overexpression of superoxide dismutase or glutathione
      peroxidase.
AB  - In this study, we developed a double-transgenic mouse model allowing hepatocyte
      specific and regulated expression of the redox-modifying enzymes copper/zinc
      superoxide dismutase (SOD) and glutathione peroxidase (GPX) by using a
      tetracycline-regulatable gene expression system. Within this system, the SOD and
      GPX level can be regulated deliberately by addition or removal of doxycycline
      hydrochloride to the drinking water. As reactive oxygen species (ROS) have been
      implicated in a number of pathological conditions, such as atherosclerosis,
      thrombosis, or liver fibrosis, processes that are also frequently associated with
      enhanced levels of plasminogen activator inhibitor-1 (PAI-1), it was the aim of
      the present study to investigate the influence of SOD and GPX overexpression on
      the regulation of PAI-1. PAI-1 mRNA and protein levels in tetracycline
      transactivator-dependent SOD-overexpressing double-transgenic mice reached values
      2.5- to threefold above the normal mRNA level. By applying doxycycline, a
      deinduction of the PAI-1 levels was observed. By using the same protocol, PAI-1
      mRNA and protein levels were enhanced in GPX double-transgenic mice, and again
      this response was blunted by the addition of doxycycline. These studies provide
      some new information regarding the role of ROS within the proteolytic processes
      in hepatocytes that require PAI-1.

PMID- 15242554
TI  - Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis.
AB  - Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative
      stress. Although some studies implicate HO-1 in modulating thrombosis after
      vascular injury, the impact of HO-1 on the rate of clot formation in vivo is
      poorly defined. This study examined the potential function of HO-1 in regulating
      platelet-dependent arterial thrombosis. Platelet-rich thrombi were induced in
      C57BL/6J mice by applying 10% ferric chloride to the exposed carotid artery. Mean
      occlusion time of wild-type mice (n = 10) was 14.6 +/- 1.0 min versus 12.9 +/-
      0.6 min for HO-1-/- mice (n = 11, p = 0.17). However, after challenge with hemin,
      mean occlusion time was significantly longer in wild-type mice (16.3 +/- 1.2 min,
      n = 15) than HO-1-/- mice (12.0 +/- 1.0 min, n = 9; p = 0.021). Hemin
      administration induced an approximately twofold increase in oxidative stress,
      measured as plasma thiobarbituric acid reactive substances. Immunohistochemical
      analysis revealed that hemin induced a robust increase in HO-1 expression within
      the carotid arterial wall. Ex vivo blood clotting within a collagen-coated
      perfusion chamber was studied to determine whether the accelerated thrombosis
      observed in HO-1-/- mice was contributed to by effects on the blood itself. Under
      basal conditions, mean clot formation during perfusion of blood over collagen did
      not differ between wild-type mice and HO-1-/- mice. However, after hemin
      challenge, mean clot formation was significantly increased in HO-1-/- mice
      compared with wild-type controls. These results suggest that, under basal
      conditions, HO-1 does not exert a significant effect on platelet-dependent clot
      formation in vivo. However, under conditions that stimulate HO-1 production,
      platelet-dependent thrombus formation is inhibited by HO-1. Enhanced HO-1
      expression in response to oxidative stress may represent an adaptive response
      mechanism to down-regulate platelet activation under prothrombotic conditions.

PMID- 15242555
TI  - The role of thiols and disulfides in platelet function.
AB  - Disulfide bonds formed in newly synthesized proteins in the endoplasmic reticulum
      of cells are important for protein structure and stability. Recent research,
      however, emphasizes a role for thiol-disulfide reactions with disulfide bond
      rearrangement as a dynamic process in cell and protein function, and in platelet
      function in particular. Protein disulfide isomerase was found on the platelet
      surface where it appears to play an important role in the platelet responses of
      aggregation and secretion, as well as activation of the platelet fibrinogen
      receptor, the alphaIIbbeta3 integrin. Additionally, sulfhydryl groups in
      alphaIIbbeta3 have been implicated in the activation of this integrin.
      Physiologic concentrations of reduced glutathione generate sulfhydryls in
      alphaIIbbeta3 and potentiate sulfhydryl-dependent reactions in alphaIIbbeta3.
      Sulfhydryl labeling in alphaIIbbeta3 is inhibited by phenylarsine oxide, a
      reagent that binds to vicinal thiols. As vicinal thiols are in equilibrium with
      disulfide bonds, they provide redox-sensitive sites in alphaIIbbeta3 able to
      respond to external or cytoplasmic reducing equivalents. Furthermore, protein
      disulfide isomerase and sulfhydryls are now implicated in platelet adhesion by a
      second platelet integrin, the alpha2beta1 collagen receptor. Most recently,
      extracellular sulfhydryls in the P2Y12 ADP receptor were found to be required for
      platelet activation by this receptor. We here provide an overview of this field
      with a focus on recent developments, and conclude with a working model.

PMID- 15242556
TI  - Oxidant stress and platelet activation in hypercholesterolemia.
AB  - Hypercholesterolemia is the dominant risk factor associated with atherothrombotic
      disorders in the western world. Consequently, much attention has been devoted to
      defining its role in the pathogenesis of atherosclerosis. It is currently
      recognized that hypercholesterolemia induces phenotypic changes in the
      microcirculation that are consistent with oxidative and nitrosative stresses.
      Superoxide is generated via several cellular systems and, once formed,
      participates in a number of reactions, yielding various free radicals, such as
      hydrogen peroxide, peroxynitrite, or oxidized low-density lipoproteins. Once
      oxidant stress is invoked, characteristic pathophysiologic features ensue, such
      as platelet activation and lipid peroxidation, which are both involved in the
      initiation and progression of the atherosclerotic lesions. Thus, therapeutic
      strategies that act to maintain the normal balance in the oxidant status of the
      vascular bed may prove effective in reducing the deleterious consequences of
      hypercholesterolemia.

PMID- 15242557
TI  - Integrins and coagulation: a role for ROS/redox signaling?
AB  - Integrin regulation and signaling play a central role in the hemostasis process,
      particularly at the level of endothelial cells by regulating the contractility
      and barrier function of these cells and in platelets by controlling adhesion and
      aggregation at the site of cell injury. Reactive oxygen species (ROS) have
      emerged as an important mediator both transducing the signals associated with
      integrin activation and modulating integrin function. Ligation of integrins in
      endothelial cells and platelets induces activation of the Ras/mitogen-activated
      protein kinase, nuclear factor-kappaB, and phosphatidylinositol 3-kinase and Rho
      GTPases pathways. Following vessel-wall injury and associated with activation and
      recruitment of platelets, there is a production of ROS concomitant with the
      stimulation of the blood coagulation. Moreover, ROS are capable of inducing
      conformational changes in integrins to change their binding affinity and
      function. This review will explore how ROS have emerged as an important modulator
      of integrins in coagulation through both outside-in (integrins stimulating ROS
      production to effect intracellular events) and inside-out signaling
      (intracellular ROS altering integrin function).

PMID- 15242558
TI  - Insights into the redox control of blood coagulation: role of vascular NADPH
      oxidase-derived reactive oxygen species in the thrombogenic cycle.
AB  - Various cardiovascular diseases including thrombosis, atherosclerosis,
      (pulmonary) hypertension and diabetes, are associated with disturbed coagulation.
      Alterations in the vessel wall common to many cardiovascular disorders have been
      shown to initiate the activity of the coagulation system, but also to be the
      result of an abnormal coagulation system. The primary link between the
      coagulation and the vascular system appears to be tissue factor (TF), which is
      induced on the surface of vascular cells and initiates the extrinsic pathway of
      the blood coagulation cascade, leading to the formation of thrombin. Thrombin can
      also interact with the vascular wall via specific receptors and can increase
      vascular TF expression. Such a "thrombogenic cycle" may be essentially involved
      in the pathogenesis of cardiovascular disorders associated with an abnormal
      coagulation. Therefore, the identification of the signaling pathways regulating
      this cycle and each of its relevant connecting links is of fundamental importance
      for the understanding of these disorders and their putative therapeutic
      potential. Reactive oxygen species (ROS) and the ROS-generating NADPH oxidases
      have been shown to play important roles as signaling molecules in the
      vasculature. In this review, we summarize the data supporting a substantial role
      of ROS in promoting a thrombogenic cycle in the vascular system.

PMID- 15242559
TI  - Oxidative stress and hypoxia: implications for plasminogen activator inhibitor-1
      expression.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of
      urokinase-type and tissue-type plasminogen activators. It has gained special
      interest among clinicians because a number of pathological conditions, such as
      myocardial infarction, atherosclerosis, thrombosis, several types of cancer, and
      the metabolic syndrome, as well as type 2 diabetes mellitus, are associated with
      increased PAI-1 levels. Interestingly, a number of these diseases are also
      accompanied by oxidative stress and the enhanced production of reactive oxygen
      species or tissue hypoxia. This article tries to summarize some aspects leading
      to enhanced PAI-1 production under oxidative stress or hypoxia.

PMID- 15242560
TI  - Preischemic selenium status as a major determinant of myocardial infarct size in
      vivo in rats.
AB  - Prospective epidemiological studies have shown that the incidence of numerous
      cardiovascular pathologies is correlated with body selenium status. However, it
      remains unclear whether selenium status also influences the outcome of myocardial
      infarction. The aim of the present study was to test whether dietary selenium
      intake affects myocardial necrosis induced by transient regional ischemia in vivo
      in rats. For this purpose, male Wistar rats received either a high-selenium (High
      Se: 1.5 mg of Se/kg) or a low-selenium (Low-Se: 0.05 mg of Se/kg) diet for 10
      weeks. Animals were subjected to 30 min of myocardial ischemia induced by
      coronary artery ligation followed by 60 min of reperfusion. Pre- and postischemic
      blood samples were collected for glutathione (GSH and GSSG) determination and for
      glutathione peroxidase (GSH-Px) assessment. Our results show that high-selenium
      intake reduces myocardial infarct size (High-Se: 25.16 +/- 1.19% versus Low-Se:
      36.51 +/- 4.14%, p < 0.05), preserves postischemic GSH/GSSG ratio (High-Se: 1.37
      +/- 0.37 versus Low-Se: 0.47 +/- 0.10, p < 0.05), increases plasma GSH-Px
      activity, and improves postischemic mean arterial pressure. In conclusion,
      preischemic body selenium status is a major determinant of the outcome of
      myocardial ischemia in vivo in rats probably because it influences the cellular
      redox status.

PMID- 15242561
TI  - Research in primary oral healthcare. Where have we been? Where are we going?

PMID- 15242562
TI  - The Effectiveness of Systemp.desensitizer in the treatment of dentine
      hypersensitivity.
AB  - PURPOSE: This study reports the effectiveness of Systemp.desensitizer (Ivoclar
      Vivadent, Schaan, Liechtenstein), when used both with and without an acid-etch
      step, in the treatment of patients with dentine hypersensitivity in UK dental
      practices. MATERIALS AND METHODS: Ten general dental practitioners (GDPs) were
      selected from two practice-based research groups. The GDPs were each requested to
      use Systemp.desensitizer in the treatment of at least ten patients who presented
      with pain due to dentine hypersensitivity. Systemp.desensitizer was applied to
      the sensitive dentine area in strict accordance with the manufacturer's handling
      instructions, except that the patients were divided into two groups. For the
      first, group NE, the procedure was to isolate the tooth, gently blot it dry with
      cotton wool pellets, rub Systemp.desensitizer into the tooth for 20 seconds, then
      gently air-dry it. For the second, group E, the procedure was identical except
      that after isolation, the treatment area was etched for 15 seconds with 35%
      phosphoric acid. Patients were asked to complete a pro forma using a 10 cm visual
      analogue scale designed to provide details of the extent of their pain before
      treatment, 24 hours post-treatment, one week post-treatment, one month post
      treatment, and three months post-treatment. The zero end of the scale was marked
      'no pain' and the 10 cm end was marked 'extreme pain'. The percentage change in
      the patients' perception of their pain, relative to pretreatment, was calculated
      using repeated measures analysis and suitable follow-up confidence intervals for
      the mean changes in perceived pain. Comparisons were then made between the
      treatment groups NE and E. RESULTS: Ninety-one patients completed the first pro
      forma and 77 completed all the pro formas. Overall, there was a significant
      reduction in pain at each of the time points after treatment but the pattern of
      pain reduction across the two groups was different. In general, the non-etched
      group (group NE) saw an 'immediate' reduction in pain which was then fairly
      consistent across the longer term, whilst, in general, the etched group (group E)
      saw less reduction in pain 24 hours after treatment, and then further reduction
      in pain at both one week and one month after treatment. Thus the non-etched group
      experienced an early reduction whilst the etched group took longer to perceive a
      reduction in pain; however, there were no statistically significant differences
      between the reductions in pain scores between the two groups at any of the time
      points after treatment. CONCLUSION: It is concluded that Systemp.desensitizer was
      effective in reducing pain from dentine hypersensitivity in the patients treated,
      and this finding was unaffected by whether or not the tooth was acid-etched prior
      to application of the reagent.

PMID- 15242563
TI  - An audit of antibiotic prescribing by vocational dental practitioners.
AB  - OBJECTIVES: To investigate antibiotic prescribing of a group of vocational dental
      practitioners (VDPs) and assess the implications for postgraduate education.
      DESIGN: A prospective audit was carried out by VDPs in general dental practice in
      2003. RESULTS: A total of seven vocational training schemes comprising 64 VDPs
      took part. Most showed some awareness of the indications for therapeutic
      prescribing but the prescribing patterns of a number were influenced by the
      pressure of time and workload and difficulty in making a definitive diagnosis.
      There were wide variations in the therapeutic antibiotic regimens used, with most
      not conforming to the guidelines available. The majority of VDPs showed a good
      understanding of the requirement for prescribing prophylactic antibiotics for
      patients with a cardiac defect but a number also prescribed when there were no
      medical indications to do so. CONCLUSIONS: From this audit it is clear that, on
      occasions, the prescribing of antibiotics by VDPs was not consistent with current
      knowledge and within the guidelines available. This calls into question the
      efficacy of present undergraduate teaching or the retention of knowledge. The
      results suggest that formal education on antibiotic prescribing in general dental
      practice should take place during the VT year.

PMID- 15242564
TI  - Rectangular collimation and radiographic efficacy in eight general dental
      practices in the West Midlands.
AB  - INTRODUCTION: Rectangular collimation is recommended in order to reduce radiation
      doses to patients. However, anecdotal reports suggest that it may result in more
      retakes, with a possible net increase in patient dosage. METHOD: To test this
      hypothesis, eight general dental practitioners were recruited to participate in a
      project. Each took 25 pairs of bitewing radiographs of patients before and 25
      after fitting rectangular collimators to their x-ray machines. Double-pack films
      were used so that duplicates could be examined. These were assessed by a
      consultant oral radiologist according to the National Radiographic Protection
      Board (NRPB) grading system for positioning and general film quality. RESULTS:
      Initially, positioning quality was above the target level for six of the eight
      dentists; however, for all but one, this dropped after using rectangular
      collimation. General film quality was of a lower overall standard initially.
      Using rectangular collimation had an effect on general film quality but the
      direction and size of this varied among the dentists. CONCLUSION: It was
      concluded that amongst the participating dentists, although numbers of retakes
      increased by 7%, there would be a net reduction in dosage to patients following
      rectangular collimation.

PMID- 15242565
TI  - An investigation of aspects of design of resin-bonded bridges in general dental
      practice and hospital services.
AB  - PURPOSE OF STUDY: To assess the design of resin-bonded bridges (RBBs) by
      dentists, the quality of information provided to a dental laboratory, and aid
      identification of best practice. DESIGN: A retrospective case series study of
      slips for RBB construction, sent by hospital and general dental practitioners to
      a dental laboratory based in a postgraduate dental institute in Scotland, UK.
      MAIN FINDINGS: 384 forms were reviewed. For single-tooth replacements, 40% of
      designs for upper anterior bridges and 46% for lower posterior bridges were fixed
      fixed (F-F) when a cantilever design was a better option. Thirty-six (9.3%) of
      RBB designs involved double abutting. On the laboratory forms, fewer than five
      (1%) cases included instructions about the thickness of the metal framework and
      in 48% there was no reference to the extension of the metal framework. PRINCIPAL
      CONCLUSIONS: For single-tooth replacements, a relatively high percentage of
      dentists prescribed a fixed-fixed design for RBBs, despite the evidence
      advocating the use of a cantilever design. A significant number of dentists used
      double abutments. The information provided to the laboratory for the construction
      of resin-bonded bridges was often insufficient.

PMID- 15242566
TI  - Lip and tongue piercing: experiences and views of general dental practitioners in
      South lancashire.
AB  - PURPOSE OF THE STUDY: To ascertain the numbers of patients with pierced lips or
      tongues seen by dentists during routine consultations. The study also examined
      the provision of advice by dentists, and the nature of piercing-related
      complications. BASIC PROCEDURE: A postal questionnaire was sent to dentists in
      two Primary Care Trust areas in South Lancashire. MAIN FINDINGS: Sixty-four of
      the 106 questionnaires were returned, giving a response rate of 60%. Sixty-two
      dentists (96.9%) reported that they had seen patients with lip or tongue
      piercings during the previous 12 months and that they had seen a mean number of
      2.8 patients with lip piercing and a mean of 9.0 patients with tongue piercing. A
      total of 56.5% of the dentists gave advice on oral hygiene and 79.0% on possible
      damage to the oral structures. Twenty-seven dentists (43.5%) said that their
      patients had oral health problems as a result of lip or tongue piercing.
      PRINCIPAL CONCLUSIONS: The dentists who responded to the questionnaire commonly
      saw lip and tongue piercings. All dentists should therefore be prepared to offer
      appropriate advice. A public health information leaflet available in all medical
      and dental practices would help to ensure that patients were better informed
      about body piercing and its complications.

PMID- 15242567
TI  - Antibody to immunoglobulin G and polyethylene glycol augment cyclic adenosine
      monophosphate production by TSH receptor antibody bound to porcine thyroid cells.
AB  - Anti-immunoglobulin G (IgG) augments cyclic adenosine monophosphate (cAMP)
      production by thyroid-blocking antibody (TBAb) bound to porcine thyroid cells
      (PTC). This is described as a conversion phenomenon. We reported the effect of
      polyethylene glycol (PEG) to augment thyroid-stimulating antibody (TSAb) activity
      in a PTC assay. In the present experiment we examined the effect of anti
      immunoglobulin G (IgG) and PEG on cAMP production from TBAb or TSAb bound to PTC.
      TBAb bound to PTC was separated from unbound TBAb by centrifugation after a first
      incubation (0.5 hour at 37 degrees C) of TBAb-IgG with PTC. TBAb bound to PTC
      were incubated with anti-human (h)IgG or hIgG fragments [F(ab')(2), Fc, Fd, H
      chain or L-chain] for 4 hours at 37 degrees C in the second incubation. Anti-IgG
      or anti-IgG fragments increased cAMP production. No conversion was caused by
      protein A, protein L, or PEG (5%). PEG did not augment cAMP production by these
      IgG antibodies. PEG augmented cAMP production during incubation of TSAb-IgG bound
      to PTC, but anti-IgG did not. PEG significantly augmented cAMP production by
      coincubation of TSAb-IgG bound to PTC and the unbound TSAb-IgG (obtained from the
      first incubation). A similar augmentative effect of PEG was also observed in
      experiments using TSAb-F(ab')(2) and TSAb-Fab. cAMP production by PTC bound by
      both TBAb- and TSAb-IgG was increased by co-incubation with anti-IgG, but was not
      increased by PEG. In conclusion, anti-IgG specifically increased cAMP production
      from TBAb bound to PTC (conversion phenomenon) and PEG specifically increased
      cAMP production by TSAb bound to PTC. Different mechanisms enhance cAMP
      production by TSAb and conversion of TBAb.

PMID- 15242569
TI  - Gene therapy for thyroid cancer: current status and future prospects.
AB  - Despite multimodality treatment for thyroid cancer, including surgical resection,
      radioiodine therapy, thyrotropin (TSH)-suppressive thyroxine treatment, and
      chemotherapy/radiotherapy, survival rates have not improved over the last
      decades. Therefore, development and evaluation of novel treatment strategies,
      including gene therapy, are urgently needed. A variety of gene therapy approaches
      have been evaluated for the treatment of follicular cell-derived and medullary
      thyroid cancer, including corrective gene therapy (p53 restoration, expression of
      a dominant negative RET mutant), cytoreductive gene therapy (suicide gene/prodrug
      strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir,
      antiangiogenic therapy with endostatin) and immunomodulatory gene therapy
      (expression of interleukin (IL)-2 and IL-12). Furthermore, cloning of the sodium
      iodide symporter (NIS) gene has paved the way for the development of a novel
      cytoreductive gene therapy strategy based on NIS gene transfer followed by the
      application of radioiodine therapy ((131)I). NIS gene delivery into medullary and
      follicular cell-derived thyroid cancer cells has been shown to be capable of
      establishing or restoring radioiodine accumulation and might therefore represent
      an effective therapy for medullary and dedifferentiated thyroid tumors that lack
      iodide accumulating activity. The data summarized in this review article clearly
      demonstrate that the currently available strategies represent potentially
      curative novel therapeutic approaches for future gene therapy of thyroid cancer.
      The combination of different therapeutic genes has been demonstrated to be very
      useful to enhance therapeutic efficacy and seems to have a promising role at
      least as part of a multimodality approach for advanced thyroid cancer.

PMID- 15242568
TI  - Increased intensities of fas expression on peripheral T-cell subsets in severe
      autoimmune thyroid disease.
AB  - Fas (CD95)-Fas ligand (FasL; CD178)-induced apoptosis is necessary for the
      maintenance of self-tolerance. To clarify whether or not any abnormalities in the
      Fas-FasL system exist in patients with autoimmune thyroid disease (AITD), we
      examined the expression of Fas and FasL on peripheral T lymphocytes by three
      color flow cytometry in 113 patients with AITD and 49 healthy controls. The
      intensities of Fas expression in both CD4(+) and CD8(+) T cells decreased in
      thyrotoxic patients with Graves' disease (GD), but increased in both patients
      with severe Hashimoto's disease (HD) undergoing treatment and seriously
      intractable patients with GD continuously positive for thyrotropin (TSH) receptor
      antibody despite treatment with antithyroid drugs for more than 5 years. The
      proportion of Fas expression was increased in CD4(+) T cells from patients with
      untreated GD, and in CD8(+) T cells from patients with severe HD. The proportion
      of CD8(+) T cells decreased in patients with severe HD. FasL were not expressed
      on T cells in controls and patients with AITD. These results indicate that (1).
      the intensities of Fas expression on peripheral T cells increase in severe
      autoimmune thyroid diseases and (2). both the intensity and the proportion of Fas
      expression may be important for the induction of apoptosis.

PMID- 15242570
TI  - Thyroid function in seventy-five healthy preterm infants thirty to thirty-five
      weeks of gestational age: a prospective and longitudinal study during the first
      year of life.
AB  - Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of
      gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine
      (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3))
      (radioimmunoassay) were measured in the mother and in the cord at delivery and in
      the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6
      months, and 12 months of postnatal age. These values were compared to those of
      healthy full-term infants of the same postnatal age (22 at 24 hours from our
      hospital and from previously reported data at others times). Mean 24-hour TSH
      values were significantly lower (p < 0.001) in preterm than in full-term infant
      populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL);
      however, all TSH values of preterm infants were in the range of the full-term
      values. Mean 24-hour free T(4) values were similar in preterm and full-term
      infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants
      had free T(4) values within the range of those of full-term infants at 24 hours.
      Mean T(4) and T(3) values were significantly lower in preterm than in full-term
      neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were
      significantly higher in preterm than in full-term newborns. From 1 week onwards,
      all thyroid function values were in the same range in both populations. In
      conclusion, individual thyroid function was similar in healthy preterms and full
      terms from the first 24 hours of life. Normative data in preterm infants during
      the first year of life applying the latest luminescence techniques currently used
      worldwide are reported.

PMID- 15242571
TI  - Subclinical hypothyroidism is associated with insulin resistance in rheumatoid
      arthritis.
AB  - We investigated the prevalence of subclinical hypothyroidism and its association
      with insulin resistance and other cardiovascular (CV) risk factors in rheumatoid
      arthritis (RA). We recorded thyroid function tests, insulin resistance markers
      comprising the Homeostasis Model Assessment for insulin resistance (HOMA-IR), the
      Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides/high
      density lipoprotein (HDL) cholesterol ratios, and other CV risk factors in 126
      patients with RA. Fifteen (12%) were taking thyroxine for hypothyroidism and 14
      (11%) had subclinical hypothyroidism (thyrotropin > 4 mU/L and normal free
      thyroxine levels). Compared to the 97 euthyroid patients, the QUICKI was lower
      and the HOMA-IR higher in treated (p = 0.031 for both) and subclinical (p = 0.004
      for both) hypothyroid cases while the triglycerides/HDL cholesterol ratios were
      higher in subclinical (p = 0.039) but not in treated hypothyroid (p = 0.365)
      cases. Treated hypothyroid patients were more often hypertensive (n = 11 [75%])
      than euthyroid patients (n = 36 [37%]) (p = 0.008). No other differences in
      characteristics were found among the three groups. After controlling for
      potentially confounding variables, subclinical hypothyroidism remained
      independently predictive of the HOMA-IR and QUICKI (p <or= 0.06) while treated
      hypothyroidism did not (p = 0.2). Subclinical hypothyroidism was commonly
      encountered and associated with insulin resistance and its related dyslipidemia
      in RA. Evaluation of thyroid function should be considered in future studies
      aimed at delineating CV risk in RA.

PMID- 15242572
TI  - Surgical treatment of Graves' disease in children.
AB  - Thyroidectomy may be indicated in children with Graves' disease who have adverse
      reactions to antithyroid drugs or who relapse after antithyroid drug therapy. We
      investigated the characteristics of childhood Graves' disease from the standpoint
      of surgical outcome. Between 1989 and 1998, 1897 patients with Graves' disease
      underwent thyroidectomy and their thyroid function could be evaluated 2 to 3
      years after thyroidectomy. The patients were divided into three groups according
      to age at thyroidectomy: 74 patients were 15 years old or less (children), 345
      patients 16 to 20 years of age (adolescents), and 1478 patients 21 years of age
      or more (adults). The children included higher proportions of patients who had a
      large goiter (> 100 g), high thyrotropin-binding inhibitory immunoglobulin (TBII)
      level (> 50%), and small remnant thyroid (< 4 g). At 2 to 3 years after
      thyroidectomy, the overt recurrence rate of the children, adolescents, and adults
      was 9.5%, 4.9%, and 5%, respectively. The cumulative recurrence-free rate of the
      children, adolescents, and adults at 5 years after thyroidectomy was 82%, 90%,
      and 92%, respectively. Surgical complications were more frequently observed in
      children. Considering the aggressiveness of childhood Graves' disease, subtotal
      thyroidectomy with thyroid remnant less than 3 g is the procedure of choice for
      preventing recurrent hyperthyroidism.

PMID- 15242573
TI  - Prognostic scoring systems in patients with follicular thyroid cancer: a
      comparison of different staging systems in predicting the patient outcome.
AB  - BACKGROUND: The use of prognostic scoring systems is important for predicting the
      survival of individuals with thyroid carcinoma. Relatively few studies have
      addressed this issue for patients with follicular thyroid cancer. The goal of
      this retrospective study was to establish the best and most pertinent prognostic
      scoring system to predict survival in patients with follicular thyroid cancer.
      METHODS: We selected 86 patients with follicular thyroid cancer treated at
      University of California, San Francisco (UCSF) hospitals from January 1954 to
      April 1998. The mean follow-up time was 11.5 years. There were 60 women (70%) and
      26 men (30%), with a mean age if 48.6 years. Prognostic scoring systems included
      tumor, node, metastases (TNM), European Organization for Research and Treatment
      of Cancer (EORTC), Age, Grade, Extent, Size (AGES), Age, Metastases, Extent, Size
      (AMES), and the Metastases, Age, Completeness of resection, Invasion, Size
      (MACIS). Survival time was calculated using the Kaplan-Meier method. Using Cox
      proportional hazards analysis, the relative importance of each scoring method was
      determined by calculating the proportion of variation in survival time explained
      (PVE). RESULTS: Kaplan-Meier analysis indicated that all scoring systems were
      significant predictors of survival time (p < 0.0001). The PVE associated with
      each system was (from highest to lowest) 0.48 for MACIS, 0.46 for AGES, 0.44 for
      EORTC, 0.40 for AMES, and 0.33 for TNM. These results indicate that the MACIS
      scoring system accounted for a great proportion of explained variance in survival
      and is a more precise predictor of survival compared to the other scoring
      systems. CONCLUSIONS: TNM, EORTC, AGES, AMES, and MACIS, all provided useful
      prognostic information about the survival in our 86 patients with follicular
      thyroid cancers. The MACIS classification, however, was the most accurate
      predictor using PVE as a method of evaluation. Future scoring systems considering
      additional prognostic factors, may obtain a higher PVE.

PMID- 15242574
TI  - Antithyroid drug-induced agranulocytosis: special reference to normal white blood
      cell count agranulocytosis.
AB  - This retrospective study was aimed at revealing the incidence of normal white
      blood cell (WBC) count agranulocytosis in patients treated with antithyroid drugs
      (ATDs). From January 1975 to December 2001, 109 patients (0.35%) presented with
      ATD-induced agranulocytosis at our clinic. In 18 patients (16.5%), the WBC count
      exceeded 3.0 x 10(9)/L at the onset of agranulocytosis. Ten showed a downward
      trend in WBC count (3.0-3.9 x 10(9)/L) after the initiation of ATDs. Four had
      symptoms of infection. In the remaining 4 patients, routine WBC and granulocyte
      count monitoring detected an agranulocytosis. During the first 3 months of ATD
      treatment, 3347 patients (10.9%) had WBC count 3.0-3.9 x 10(9)/L even once with
      no symptom and normal granulocyte count and 26672 patients had WBC count >or= 4.0
      x 10(9)/L with no symptom and normal granulocyte count. When agranulocytosis was
      found, twelve patients with normal WBC count agranulocytosis (0.36%) had WBC
      count 3.0-3.9 x 10(9)/L with no symptom, whereas only 2 patients with
      agranulocytosis (0.008%) had WBC count >or= 4.0 x 10(9)/L with no symptom. In
      conclusion, clinicians should take normal WBC count agranulocytosis into
      consideration at least during the first 3 months of antithyroid drug therapy,
      especially when WBC count is 3.0-3.9 x 10(9)/L.

PMID- 15242575
TI  - Subcutaneous administration of recombinant human thyrotropin as an alternative to
      thyroid hormone withdrawal in patients with anticoagulated thyroid cancer:
      preliminary results.
AB  - For patients with thyroid cancer taking anticoagulants, because of hematoma risk
      at the injection site, intramuscular injections (IM) of recombinant human
      thyrotropin (rhTSH) are usually avoided and patients remain hypothyroid. The aim
      of the present study was to evaluate if subcutaneous injections (SC) of rhTSH are
      an alternative to IM. Five consecutive patients receiving anticoagulants were
      evaluated. The dose regimen was similar to the traditional follow-up protocol (2
      x 0.9 mg, SC route). rhTSH administration elicited a sharp and prompt increase in
      serum TSH that peaked at day 3 (24 hours after the second rhTSH injection), with
      mean values of 246 +/- 68 mU/L. In one patient with a large thyroid remnant,
      thyroglobulin (Tg) rose from 18 ng/mL to 450 ng/mL. No adverse effects were
      observed. We conclude that SC injection of rhTSH represents a safe and efficient
      procedure in the monitoring of patients with thyroid cancer taking
      anticoagulants.

PMID- 15242576
TI  - Lack of efficacy of recombinant human thyrotropin versus thyroid hormone
      withdrawal for radioiodine therapy imaging in a patient with differentiated
      thyroid carcinoma lung metastases.
AB  - The treatment of lung metastases of thyroid cancer is nearly exclusively limited
      to the administration of iodine-131. For patients presented with micronodular
      lesions, the therapeutic response is often excellent, increasing life expectancy.
      Because of the necessity of multiple iodine-131 treatments in the course of this
      therapy, and subsequently, the lack of tolerance of hormonal withdrawal, the use
      of recombinant human thyrotropin (rhTSH) as a method of stimulation could
      represent an interesting alternative. However, as in the present case, the
      stimulation by rhTSH can be less effective than hormonal withdrawal, as shown in
      the posttherapy scan to detect metastatic lesions and thus could be detrimental
      to the treatment efficiency.

PMID- 15242577
TI  - Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary
      thyroid carcinoma.
AB  - OBJECTIVE: Medullary thyroid carcinoma (MTC) originates from C-cells. A wide
      variety of tumor markers including calcitonin (CT), carcinoembryonic antigen
      (CEA), and chromogranin A are produced by MTC. Surgery remains the only
      potentially curative therapy, and early detection of the primary remains the most
      important prognostic factor for a positive outcome for the patient. The following
      case concerns a 50-year-old woman with histologically proven MTC, who completely
      lacked serum elevation of both CT and CEA. METHODS: We performed a total
      thyroidectomy with lymphadenectomy in the central compartment. Histologic
      sections were stained for CT, CEA, and chromogranin A. Additionally we examined
      the patient's blood for mutations in the RET proto-oncogene. RESULTS: Serum CT
      and CEA were below the detection level in the serum. The tumor showed weak
      staining for CT, but strong staining for CEA and chromogranin A. Sequencing of
      the RET-proto-oncogene revealed no mutations. Five years after the operation, the
      patient remains well and shows no signs of tumor recurrence. CONCLUSIONS: We
      hereby report of a patient with neither plasma elevation of CT nor CEA. From the
      clinical standpoint, it is important to determine how this subgroup of MTC should
      be followed because CT and CEA are of no clinical use.

PMID- 15242578
TI  - Cryptococcal thyroiditis and hyperthyroidism.
AB  - We report a case of cryptococcal thyroiditis presenting with hyperthyroidism that
      evolved through a transient euthyroid phase to hypothyroidism and finally
      recovered to normal function. This four-phase clinical presentation is similar to
      that of subacute thyroiditis, and it is unusual in the setting of infectious
      nonviral thyroiditis. Cryptococcal thyroiditis is rare; only three cases have
      been reported. Our patient is the first who survived the disseminated
      cryptococcal infection with thyroid involvement, thus enabling longitudinal
      clinical and endocrinologic follow-up.

PMID- 15242579
TI  - Activation of thyroid tissue in thyroglossal duct.

PMID- 15242580
TI  - Progression of subacute (de Quervain's) thyroiditis into Hashimoto's thyroiditis.

PMID- 15242581
TI  - Increased TBG during pregnancy and increased hormonal requirements.

PMID- 15242582
TI  - How to kill an enzyme (in more ways than one).

PMID- 15242583
TI  - Visualizing the house from the brick.

PMID- 15242584
TI  - siRNAs at RISC.

PMID- 15242585
TI  - Attack of the killer tomato pathogens.

PMID- 15242586
TI  - Intra-protein proton transfer; presentation of the most massive flux in the
      biosphere at quantum chemistry resolution.

PMID- 15242587
TI  - Structurally analogous proteins do exist!

PMID- 15242588
TI  - A novel approach to high-throughput screening; a solution for structural
      genomics?

PMID- 15242589
TI  - Seeing GroEL at 6 A resolution by single particle electron cryomicroscopy.
AB  - We present a reconstruction of native GroEL by electron cryomicroscopy (cryo-EM)
      and single particle analysis at 6 A resolution. alpha helices are clearly visible
      and beta sheet density is also visible at this resolution. While the overall
      conformation of this structure is quite consistent with the published X-ray data,
      a measurable shift in the positions of three alpha helices in the intermediate
      domain is observed, not consistent with any of the 7 monomeric structures in the
      Protein Data Bank model (1OEL). In addition, there is evidence for slight
      rearrangement or flexibility in parts of the apical domain. The 6 A resolution
      cryo-EM GroEL structure clearly demonstrates the veracity and expanding scope of
      cryo-EM and the single particle reconstruction technique for macromolecular
      machines.

PMID- 15242590
TI  - Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT
      domains.
AB  - BRCT tandem domains, found in many proteins involved in DNA damage checkpoint and
      DNA repair pathways, were recently shown to be phosphopeptide binding motifs.
      Using solution nuclear magnetic resonance (NMR) spectroscopy and mutational
      analysis, we have characterized the interaction of BRCA1-BRCT domains with a
      phosphoserine-containing peptide derived from the DNA repair helicase BACH1. We
      show that a phenylalanine in the +3 position from the phosphoserine of BACH1 is
      bound to a conserved hydrophobic pocket formed between the two BRCT domains and
      that recognition of the phosphate group is mediated by lysine and serine side
      chains from the amino-terminal BRCT domain. Mutations that prevent phosphopeptide
      binding abolish BRCA1 function in DNA damage-induced checkpoint control. Our NMR
      data also reveal a dynamic interaction between BRCA1-BRCT and BACH1, where the
      bound phosphopeptide exists as an equilibrium of two conformations and where
      BRCA1-BRCT undergoes a transition to a more rigid conformation upon peptide
      binding.

PMID- 15242592
TI  - West Nile virus core protein; tetramer structure and ribbon formation.
AB  - We have determined the crystal structure of the core (C) protein from the Kunjin
      subtype of West Nile virus (WNV), closely related to the NY99 strain of WNV,
      currently a major health threat in the U.S. WNV is a member of the Flaviviridae
      family of enveloped RNA viruses that contains many important human pathogens. The
      C protein is associated with the RNA genome and forms the internal core which is
      surrounded by the envelope in the virion. The C protein structure contains four
      alpha helices and forms dimers that are organized into tetramers. The tetramers
      form extended filamentous ribbons resembling the stacked alpha helices seen in
      HEAT protein structures.

PMID- 15242591
TI  - Structures of sortase B from Staphylococcus aureus and Bacillus anthracis reveal
      catalytic amino acid triad in the active site.
AB  - Surface proteins attached by sortases to the cell wall envelope of bacterial
      pathogens play important roles during infection. Sorting and attachment of these
      proteins is directed by C-terminal signals. Sortase B of S. aureus recognizes a
      motif NPQTN, cleaves the polypeptide after the Thr residue, and attaches the
      protein to pentaglycine cross-bridges. Sortase B of B. anthracis is thought to
      recognize the NPKTG motif, and attaches surface proteins to m-diaminopimelic acid
      cross-bridges. We have determined crystal structure of sortase B from B.
      anthracis and S. aureus at 1.6 and 2.0 A resolutions, respectively. These
      structures show a beta-barrel fold with alpha-helical elements on its outside, a
      structure thus far exclusive to the sortase family. A putative active site
      located on the edge of the beta-barrel is comprised of a Cys-His-Asp catalytic
      triad and presumably faces the bacterial cell surface. A putative binding site
      for the sorting signal is located nearby.

PMID- 15242593
TI  - Joint X-ray and NMR refinement of the yeast L30e-mRNA complex.
AB  - L30e, a Saccharomyces cervisiae ribosomal protein, regulates its own expression
      by binding to a purine-rich asymmetric internal loop located in both its pre-mRNA
      and mature mRNA. A crystal structure of an MBP-L30e fusion protein in complex
      with an RNA containing the pre-mRNA regulatory site was solved at 3.24 A.
      Interestingly, the structure of the RNA differed from that observed in a
      previously determined NMR structure of the complex. Analysis of the NMR data led
      to the identification of a single imino proton resonance in the internal loop
      that had been incorrectly assigned and was principally responsible for the
      erroneous RNA structure. A structure refinement was performed using both the X
      ray diffraction data and the NMR-derived distance and angle restraints. The joint
      NMR and X-ray refinement resulted in improved stereochemistry and lower
      crystallographic R factors. The RNA internal loop of the MBP-L30e-mRNA complex
      adopts the canonical K-turn fold.

PMID- 15242594
TI  - Ab initio structure determination and functional characterization of CBM36; a new
      family of calcium-dependent carbohydrate binding modules.
AB  - The enzymatic degradation of polysaccharides harnesses multimodular enzymes whose
      carbohydrate binding modules (CBM) target the catalytic domain onto the
      recalcitrant substrate. Here we report the ab initio structure determination and
      subsequent refinement, at 0.8 A resolution, of the CBM36 domain of the
      Paenibacillus polymyxa xylanase 43A. Affinity electrophoresis, isothermal
      titration calorimetry, and UV difference spectroscopy demonstrate that CBM36 is a
      novel Ca(2+)-dependent xylan binding domain. The 3D structure of CBM36 in complex
      with xylotriose and Ca(2+), at 1.5 A resolution, displays significant
      conformational changes compared to the native structure and reveals the molecular
      basis for its unique Ca(2+)-dependent binding of xylooligosaccharides through
      coordination of the O2 and O3 hydroxyls. CBM36 is one of an emerging spectrum of
      carbohydrate binding modules that increasingly find applications in industry and
      display great potential for mapping the "glyco-architecture" of plant cells.

PMID- 15242595
TI  - Crystal structure of human vinculin.
AB  - Alterations in the actin cytoskeleton following the formation of cell-matrix and
      cell-cell junctions are orchestrated by vinculin. Vinculin associates with a
      large number of cytoskeletal and signaling proteins, and this flexibility is
      thought to contribute to rapid dissociation and reassociations of adhesion
      complexes. Intramolecular interactions between vinculin's head (Vh) and tail (Vt)
      domains limit access of its binding sites for other adhesion proteins. While the
      crystal structures of the Vh and Vt domains are known, these domains represent
      less than half of the entire protein and are separated by a large central region
      of unknown structure and function. Here we report the crystal structure of human
      full-length vinculin to 2.85 A resolution. In its resting state, vinculin is a
      loosely packed collection of alpha-helical bundles held together by Vh-Vt
      interactions. The three new well ordered alpha-helical bundle domains are similar
      in their structure to either Vh (Vh2 and Vh3) or to Vt (Vt2) and their loose
      packing provides the necessary flexibility that allows vinculin to interact with
      its various protein partners at sites of cell adhesion.

PMID- 15242596
TI  - Structure of a lipid droplet protein; the PAT family member TIP47.
AB  - The perilipin/ADRP/TIP47 (PAT) proteins localize to the surface of intracellular
      neutral lipid droplets. Perilipin is essential for lipid storage and hormone
      regulated lipolysis in adipocytes, and perilipin null mice exhibit a dramatic
      reduction in adipocyte lipid stores. A significant fraction of the approximately
      200 amino acid N-terminal region of the PAT proteins consists of 11-mer helical
      repeats that are also found in apolipoproteins and other lipid-associated
      proteins. The C-terminal 60% of TIP47, a representative PAT protein, comprises a
      monomeric and independently folded unit. The crystal structure of the C-terminal
      portion of TIP47 was determined and refined at 2.8 A resolution. The structure
      consists of an alpha/beta domain of novel topology and a four-helix bundle
      resembling the LDL receptor binding domain of apolipoprotein E. The structure
      suggests an analogy between PAT proteins and apolipoproteins in which helical
      repeats interact with lipid while the ordered C-terminal region is involved in
      protein:protein interactions.

PMID- 15242597
TI  - Tandem repeat of a seven-bladed beta-propeller domain in oligoxyloglucan reducing
      end-specific cellobiohydrolase.
AB  - Oligoxyloglucan reducing-end-specific cellobiohydrolase (OXG-RCBH; EC 3.2.1.150)
      is an exoglucanase that recognizes the reducing end of oligoxyloglucan and
      releases two glucosyl residue segments from the main chain. The X-ray crystal
      structure of OXG-RCBH determined at 2.2 A resolution reveals a unique feature of
      this enzyme; OXG-RCBH consists of a tandem repeat of two similar domains, which
      are both folded into seven-bladed beta-propeller structures. The sequence
      alignment of the propeller blades, based on the structure, indicates that a weak
      repeat of the amino acid sequence occurred seven times to construct each domain.
      There is a cleft that can accommodate the substrate oligosaccharide between the
      two domains, which is a putative substrate binding subsite. Mutation of either
      Asp35 or Asp465, located in the putative catalytic center, to Asn resulted in a
      protein with no detectable catalytic activity, indicating the critical role of
      these amino acids in catalysis.

PMID- 15242598
TI  - Automated analysis of vapor diffusion crystallization drops with an X-ray beam.
AB  - Crystallogenesis, usually based on the vapor diffusion method, is currently
      considered one of the most difficult steps in macromolecular X-ray
      crystallography. Due to the increasing number of crystallization assays performed
      by protein crystallographers, several automated analysis methods are under
      development. Most of these methods are based on microscope images and shape
      recognition. We propose an alternative method of identifying protein crystals: by
      directly exposing the crystallization drops to an X-ray beam. The resulting
      diffraction provides far more information than classical microscope images. Not
      only is the presence of diffracting crystals revealed, but also a first
      estimation of the space group, cell parameters, and mosaicity is obtained. In
      certain cases, it is also possible to collect enough data to verify the presence
      of a specific substrate or a heavy atom. All these steps are performed without
      the sometimes tedious necessity of removing crystals from their crystallization
      drop.

PMID- 15242599
TI  - Structure of an anti-Lewis X Fab fragment in complex with its Lewis X antigen.
AB  - The Lewis X trisaccharide is pivotal in mediating specific cell-cell
      interactions. Monoclonal antibody 291-2G3-A, which was generated from mice
      infected with schistosomes, has been shown to recognize the Lewis X
      trisaccharide. Here we describe the structure of the Fab fragment of 291-2G3-A,
      with Lewis X, to 1.8 A resolution. The crystallographic analysis revealed that
      the antigen binding site is a rather shallow binding pocket, and residues from
      all six complementary determining regions of the antibody contact all sugar
      residues. The high specificity of the binding pocket does not result in high
      affinity; the K(D) determined by isothermal calorimetry is 11 microM. However,
      this affinity is in the same range as for other sugar-antibody complexes. The
      detailed understanding of the antibody-Lewis X interaction revealed by the
      crystal structure may be helpful in the design of better diagnostic tools for
      schistosomiasis and for studying Lewis X-mediated cell-cell interactions by
      antibody interference.

PMID- 15242600
TI  - Structural differences in the DNA binding domains of human p53 and its C. elegans
      ortholog Cep-1.
AB  - The DNA binding domains of human p53 and Cep-1, its C. elegans ortholog,
      recognize essentially identical DNA sequences despite poor sequence similarity.
      We solved the three-dimensional structure of the Cep-1 DNA binding domain in the
      absence of DNA and compared it to that of human p53. The two domains have similar
      overall folds. However, three loops, involved in DNA and Zn binding in human p53,
      contain small alpha helices in Cep-1. The alpha helix in loop L3 of Cep-1 orients
      the side chains of two conserved arginines toward DNA; in human p53, both
      arginines are mutation hotspots, but only one contacts DNA. The alpha helix in
      loop L1 of Cep-1 repositions the entire loop, making it unlikely for residues of
      this loop to contact bases in the major groove of DNA, as occurs in human p53.
      Thus, during evolution there have been considerable changes in the structure of
      the p53 DNA binding domain.

PMID- 15242601
TI  - Pathway complexity of Alzheimer's beta-amyloid Abeta16-22 peptide assembly.
AB  - Recent studies suggest that both soluble oligomers and insoluble fibrils have
      toxic effects in cell cultures, raising the interest in determining the first
      steps of the assembly process. We have determined the aggregation mechanisms of
      Abeta(16-22) dimer using the activation-relaxation technique and an approximate
      free energy model. Consistent with the NMR solid-state analysis, the dimer is
      predicted to prefer an antiparallel beta sheet structure with the expected
      registry of intermolecular hydrogen bonds. The simulations, however, locate three
      other antiparallel minima with nonnative beta sheet registries and one parallel
      beta sheet structure, slightly destabilized with respect to the ground state.
      This result is significant because it can explain the observed dependency of beta
      sheet registry on pH conditions. We also find that assembly of Abeta(16-22) into
      dimers follows multiple routes, but alpha-helical intermediates are not
      obligatory. This indicates that destabilization of alpha-helical intermediates is
      unlikely to abolish oligomerization of Abeta peptides.

PMID- 15242602
TI  - The solution structure of type III effector protein AvrPto reveals conformational
      and dynamic features important for plant pathogenesis.
AB  - Pseudomonas syringae pv. tomato, the causative agent of bacterial speck disease
      of tomato, uses a type III secretion system (TTSS) to deliver effector proteins
      into the host cell. In resistant plants, the bacterial effector protein AvrPto
      physically interacts with the host Pto kinase and elicits antibacterial defense
      responses. In susceptible plants, which lack the Pto kinase, AvrPto acts as a
      virulence factor to promote bacterial growth. The solution structure of AvrPto
      reveals a functional core consisting of a three-helix bundle motif flanked by
      disordered N- and C-terminal tails. Residues required for Pto binding lie in a 19
      residue Omega loop. Modeling suggests a hydrophobic patch involving the
      activation loop of Pto forms a contact surface with the AvrPto Omega loop and
      that helix packing mediates interactions between AvrPto and putative virulence
      targets Api2 and Api3. The AvrPto structure has a low stability that may
      facilitate chaperone-independent secretion by the TTSS.

PMID- 15242603
TI  - Crystal structure of activated HutP; an RNA binding protein that regulates
      transcription of the hut operon in Bacillus subtilis.
AB  - HutP is an L-histidine-activated RNA binding protein that regulates the
      expression of the histidine utilization (hut) operon in Bacillus subtilis by
      binding to cis-acting regulatory sequences on the hut mRNA. The crystal structure
      of HutP complexed with an L-histidine analog showed a novel fold; there are four
      antiparallel beta strands in the central region of each monomer, with two alpha
      helices each on the front and back. Two HutP monomers form a dimer, and three
      dimers are arranged in crystallographic 3-fold symmetry to form a hexamer. A
      histidine analog was located in between the two monomers of HutP, with the
      imidazole group of L-histidine hydrogen bonded to Glu81. An activation mechanism
      is proposed based on the identification of key residues of HutP. The HutP binding
      region in hut mRNA was defined: it consists of three UAG trinucleotide motifs
      separated by four spacer nucleotides. Residues of HutP potentially important for
      RNA binding were identified.

PMID- 15242604
TI  - Mechanism of primary proton transfer in bacteriorhodopsin.
AB  - Recent structures of putative intermediates in the bacteriorhodopsin photocycle
      have provided valuable snapshots of the mechanism by which protons are pumped
      across the membrane. However, key steps remain highly controversial, particularly
      the proton transfer occurring immediately after retinal trans-->cis
      photoisomerization. The gradual release of stored energy is inherently
      nonequilibrium: which photocycle intermediates are populated depends not only on
      their energy but also on their interconversion rates. To understand why the
      photocycle follows a productive (i.e., pumping), rather than some unproductive,
      relaxation pathway, it is necessary to know the relative energy barriers of
      individual steps. To discriminate between the many proposed scenarios of this
      process, we computed all its possible minimum-energy paths. This reveals that not
      one, but three very different pathways have energy barriers consistent with
      experiment. This result reconciles the conflicting views held on the mechanism
      and suggests a strategy by which the protein renders this essential step
      resilient.

PMID- 15242605
TI  - Convergent recognition of the IgE binding site on the high-affinity IgE receptor.
AB  - Two structurally distinct classes of peptides were recently identified by phage
      display that bind the high-affinity IgE receptor, FcepsilonRI, and block IgE
      binding and subsequent receptor activation. Both classes adopt highly stable
      structures in solution, one forming a beta hairpin, with the other forming a
      helical "zeta" structure. Despite these differences, the two classes bind
      competitively to the same site on the receptor. Structural analyses of both
      peptide-receptor complexes by NMR spectroscopy and/or X-ray crystallography
      reveal that the unrelated peptide scaffolds have nevertheless converged to
      present a similar three-dimensional surface to interact with FcepsilonRI and that
      their modes of interaction share a key feature of the IgE-FcepsilonRI complex,
      the proline/tryptophan sandwich.

PMID- 15242606
TI  - Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary
      form of hypertension.
AB  - WNK kinases comprise a small group of unique serine/threonine protein kinases
      that have been genetically linked to pseudohypoaldosteronism type II, an
      autosomal dominant form of hypertension. Here we present the structure of the
      kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation.
      A lysine residue (Lys-233) is found in the active site emanating from strand
      beta2 rather than strand beta3 as in other protein kinases. The activation loop
      adopts a unique well-folded inactive conformation. The conformations of the P+1
      specificity pocket, the placement of the conserved active site threonine (Thr
      386), and the exterior placement of helix C, contribute to the low activity
      state. By homology modeling, we identified two hydrophobic residues in the
      substrate-binding groove that contribute to substrate specificity. The structure
      of the WNK1 catalytic domain, with its unique active site, may help in the design
      of therapeutic reagents for the treatment of hypertension.

PMID- 15242607
TI  - 1.2 A crystal structure of the serine carboxyl proteinase pro-kumamolisin;
      structure of an intact pro-subtilase.
AB  - Kumamolisin, an extracellular proteinase derived from an acido/thermophilic
      Bacillus, belongs to the sedolisin family of endopeptidases characterized by a
      subtilisin-like fold and a Ser-Glu-Asp catalytic triad. In kumamolisin, the Asp82
      carboxylate hydrogen bonds to Glu32-Trp129, which might act as a proton sink
      stabilizing the catalytic residues. The 1.2/1.3 A crystal structures of the Glu32
      ->Ala and Trp129-->Ala mutants show that both mutations affect the active-site
      conformation, causing a 95% activity decrease. In addition, the 1.2 A crystal
      structure of the Ser278-->Ala mutant of pro-kumamolisin was determined. The
      prodomain exhibits a half-beta sandwich core docking to the catalytic domain
      similarly as the equivalent subtilisin prodomains in their catalytic-domain
      complexes. This pro-kumamolisin structure displays, for the first time, the
      uncleaved linker segment running across the active site and connecting the
      prodomain with the properly folded catalytic domain. The structure strongly
      points to an initial intramolecular activation cleavage in subtilases, as
      presumed for pro-subtilisin and pro-furin.

PMID- 15242608
TI  - Structural snapshots of human HDAC8 provide insights into the class I histone
      deacetylases.
AB  - Modulation of the acetylation state of histones plays a pivotal role in the
      regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal
      of acetyl groups from lysines near the N termini of histones. This reaction
      promotes the condensation of chromatin, leading to repression of transcription.
      HDAC deregulation has been linked to several types of cancer, suggesting a
      potential use for HDAC inhibitors in oncology. Here we describe the first crystal
      structures of a human HDAC: the structures of human HDAC8 complexed with four
      structurally diverse hydroxamate inhibitors. This work sheds light on the
      catalytic mechanism of the HDACs, and on differences in substrate specificity
      across the HDAC family. The structure also suggests how phosphorylation of Ser39
      affects HDAC8 activity.

PMID- 15242609
TI  - Differential corticostriatal plasticity during fast and slow motor skill learning
      in mice.
AB  - BACKGROUND: Motor skill learning usually comprises "fast" improvement in
      performance within the initial training session and "slow" improvement that
      develops across sessions. Previous studies have revealed changes in activity and
      connectivity in motor cortex and striatum during motor skill learning. However,
      the nature and dynamics of the plastic changes in each of these brain structures
      during the different phases of motor learning remain unclear. RESULTS: By using
      multielectrode arrays, we recorded the simultaneous activity of neuronal
      ensembles in motor cortex and dorsal striatum of mice during the different phases
      of skill learning on an accelerating rotarod. Mice exhibited fast improvement in
      the task during the initial session and also slow improvement across days.
      Throughout training, a high percentage of striatal (57%) and motor cortex (55%)
      neurons were task related; i.e., changed their firing rate while mice were
      running on the rotarod. Improvement in performance was accompanied by substantial
      plastic changes in both striatum and motor cortex. We observed parallel
      recruitment of task-related neurons in both structures specifically during the
      first session. Conversely, during slow learning across sessions we observed
      differential refinement of the firing patterns in each structure. At the neuronal
      ensemble level, we observed considerable changes in activity within the first
      session that became less evident during subsequent sessions. CONCLUSIONS: These
      data indicate that cortical and striatal circuits exhibit remarkable but
      dissociable plasticity during fast and slow motor skill learning and suggest that
      distinct neural processes mediate the different phases of motor skill learning.

PMID- 15242610
TI  - The hereditary spastic paraplegia gene, spastin, regulates microtubule stability
      to modulate synaptic structure and function.
AB  - BACKGROUND: Hereditary Spastic Paraplegia (HSP) is a devastating neurological
      disease causing spastic weakness of the lower extremities and eventual axonal
      degeneration. Over 20 genes have been linked to HSP in humans; however, mutations
      in one gene, spastin (SPG4), are the cause of >40% of all cases. Spastin is a
      member of the ATPases associated with diverse cellular activities (AAA) protein
      family, and contains a microtubule interacting and organelle transport (MIT)
      domain. Previous work in cell culture has proposed a role for Spastin in
      regulating microtubules. RESULTS: Employing Drosophila transgenic methods for
      overexpression and RNA interference (RNAi), we have investigated the role of
      Spastin in vivo. We show that Drosophila Spastin (D-Spastin) is enriched in axons
      and synaptic connections. At neuromuscular junctions (NMJ), Dspastin RNAi causes
      morphological undergrowth and reduced synaptic area. Moreover, Dspastin
      overexpression reduces synaptic strength, whereas Dspastin RNAi elevates synaptic
      currents. By using antibodies against posttranslationally modified alpha-Tubulin,
      we find that Dspastin regulates microtubule stability. Functional synaptic
      defects caused by Dspastin RNAi and overexpression were pharmacologically
      alleviated by agents that destabilize and stabilize microtubules, respectively.
      CONCLUSIONS: Loss of Dspastin in Drosophila causes an aberrantly stabilized
      microtubule cytoskeleton in neurons and defects in synaptic growth and
      neurotransmission. These in vivo data strongly support previous reports,
      providing a probable cause for the neuronal dysfunction in spastin-linked HSP
      disease. The role of Spastin in regulating neuronal microtubule stability
      suggests therapeutic targets for HSP treatment and may provide insight into
      neurological disorders linked to microtubule dysfunction.

PMID- 15242611
TI  - A phylogenetically based secondary structure for the yeast telomerase RNA.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein complex whose RNA moiety dictates
      the addition of specific simple sequences onto chromosomes ends. While relevant
      for certain human genetic diseases, the contribution of the essential telomerase
      RNA to RNP assembly still remains unclear. Phylogenetic analyses of vertebrate
      and ciliate telomerase RNAs revealed conserved elements that potentially organize
      protein subunits for RNP function. In contrast, the yeast telomerase RNA could
      not be fitted to any known structural model, and the limited number of known
      sequences from Saccharomyces species did not permit the prediction of a yeast
      specific conserved structure. RESULTS: We cloned and analyzed the complete
      telomerase RNA loci (TLC1) from all known Saccharomyces species belonging to the
      "sensu stricto" group. Complementation analyses in S. cerevisiae and end mappings
      of mature RNAs ensured the relevance of the cloned sequences. By using
      phylogenetic comparative analysis coupled with in vitro enzymatic probing, we
      derived a secondary structure prediction of the Saccharomyces cerevisiae TLC1
      RNA. This conserved secondary structure prediction includes a central domain that
      is likely to orchestrate DNA synthesis and at least two accessory domains
      important for RNA stability and telomerase recruitment. The structure also
      reveals a potential tertiary interaction between two loops in the central core.
      CONCLUSIONS: The predicted secondary structure of the TLC1 RNA of S. cerevisiae
      reveals a distinct folding pattern featuring well-separated but conserved
      functional elements. The predicted structure now allows for a detailed and
      rationally designed study to the structure-function relationships within the
      telomerase RNP-complex in a genetically tractable system.

PMID- 15242612
TI  - Butterfly wing pattern evolution is associated with changes in a Notch/Distal
      less temporal pattern formation process.
AB  - In butterflies there is a class of "intervein" wing patterns that have lines of
      symmetry halfway between wing veins. These patterns occur in a range of shapes,
      including eyespots, ellipses, and midlines, and were proposed to have evolved
      through developmental shifts along a midline-to-eyespot continuum. Here we show
      that Notch (N) upregulation, followed by activation of the transcription factor
      Distal-less (Dll), is an early event in the development of eyespot and intervein
      midline patterns across multiple species of butterflies. A relationship between
      eyespot phenotype and N and Dll expression is demonstrated in a loss-of-eyespot
      mutant in which N and Dll expression is reduced at missing eyespot sites. A
      phylogenetic comparison of expression time series from eight moth and butterfly
      species suggests that intervein N and Dll patterns are a derived characteristic
      of the butterfly lineage. Furthermore, prior to eyespot determination in eyespot
      bearing butterflies, N and Dll are transiently expressed in a pattern that
      resembles ancestral intervein midline patterns. In this study we establish N
      upregulation as the earliest known event in eyespot determination, demonstrate
      gene expression associated with intervein midline color patterns, and provide
      molecular evidence that wing patterns evolved through addition to and truncation
      of a conserved midline-to-eyespot pattern formation sequence.

PMID- 15242613
TI  - FtsZ exhibits rapid movement and oscillation waves in helix-like patterns in
      Escherichia coli.
AB  - Prokaryotes contain cytoskeletal proteins such as the tubulin-like FtsZ, which
      forms the Z ring at the cell center for cytokinesis, and the actin-like MreB,
      which forms a helix along the long axis of the cell and is required for shape
      maintenance. Using time-lapse analysis of Escherichia coli cells expressing FtsZ
      GFP, we found that FtsZ outside of the Z ring also localized in a helix-like
      pattern and moved very rapidly within this pattern. The movement occurred
      independently of the presence of Z rings and was most easily detectable in cells
      lacking Z rings. Moreover, we observed oscillation waves of FtsZ-GFP in the helix
      like pattern, particularly in elongated cells, and the period of this oscillation
      was similar to that of the Min proteins. The MreB helix was not required for the
      rapid movement of FtsZ or the oscillation of MinD. The results suggest that FtsZ
      not only forms the Z ring but also is part of a highly dynamic, potentially
      helical cytoskeleton in bacterial cells.

PMID- 15242614
TI  - Spatial coding of the predicted impact location of a looming object.
AB  - Avoiding or intercepting looming objects implies a precise estimate of both time
      until contact and impact location. In natural situations, extrapolating a
      movement trajectory relative to some egocentric landmark requires taking into
      account variations in retinal input associated with moment-to-moment changes in
      body posture. Here, human observers predicted the impact location on their face
      of an approaching stimulus mounted on a robotic arm, while we systematically
      manipulated the relation between eye, head, and trunk orientation. The projected
      impact point on the observer's face was estimated most accurately when the target
      originated from a location aligned with both the head and eye axes. Eccentric
      targets with respect to either axis resulted in a systematic perceptual bias
      ipsilateral to the trajectory's origin. We conclude that (1) predicting the
      impact point of a looming target requires combining retinal information with eye
      position information, (2) that this computation is accomplished accurately for
      some, but not all, possible combinations of these cues, (3) that the
      representation of looming trajectories is not formed in a single, canonical
      reference frame, and (4) that the observed perceptual biases could reflect an
      automatic adaptation for interceptive/defensive actions within near peripersonal
      space.

PMID- 15242615
TI  - Positioning and elongation of the fission yeast spindle by microtubule-based
      pushing.
AB  - In eukaryotic cells, proper position of the mitotic spindle is necessary for
      successful cell division and development. We explored the nature of forces
      governing the positioning and elongation of the mitotic spindle in
      Schizosaccharomyces pombe. We hypothesized that astral microtubules exert
      mechanical force on the S. pombe spindle and thus help align the spindle with the
      major axis of the cell. Microtubules were tagged with green fluorescent protein
      (GFP) and visualized by two-photon microscopy. Forces were inferred both from
      time-lapse imaging of mitotic cells and, more directly, from mechanical
      perturbations induced by laser dissection of the spindle and astral microtubules.
      We found that astral microtubules push on the spindle poles in S. pombe, in
      contrast to the pulling forces observed in a number of other cell types. Further,
      laser dissection of the spindle midzone induced spindle collapse inward. This
      offers direct evidence in support of the hypothesis that spindle elongation is
      driven by the sliding apart of antiparallel microtubules in the spindle midzone.
      Broken spindles recovered and mitosis completed as usual. We propose a model of
      spindle centering and elongation by microtubule-based pushing forces.

PMID- 15242616
TI  - Regulation of sister chromatid cohesion between chromosome arms.
AB  - Sister chromatid separation in anaphase depends on the removal of cohesin
      complexes from chromosomes. In vertebrates, the bulk of cohesin is already
      removed from chromosome arms during prophase and prometaphase, whereas cohesin
      remains at centromeres until metaphase, when cohesin is cleaved by the protease
      separase. In unperturbed mitoses, arm cohesion nevertheless persists throughout
      metaphase and is principally sufficient to maintain sister chromatid cohesion.
      How arm cohesion is maintained until metaphase is unknown. Here we show that
      small amounts of cohesin can be detected in the interchromatid region of
      metaphase chromosome arms. If prometaphase is prolonged by treatment of cells
      with microtubule poisons, these cohesin complexes dissociate from chromosome
      arms, and arm cohesion is dissolved. If cohesin dissociation in prometaphase
      arrested cells is prevented by depletion of Plk1 or inhibition of Aurora B, arm
      cohesion is maintained. These observations imply that, in unperturbed mitoses,
      small amounts of cohesin maintain arm cohesion until metaphase. When cells
      lacking Plk1 and Aurora B activity enter anaphase, chromatids lose cohesin. This
      loss is prevented by proteasome inhibitors, implying that it depends on separase
      activation. Separase may therefore be able to cleave cohesin at centromeres and
      on chromosome arms.

PMID- 15242617
TI  - Microtubule dynamics are necessary for SRC family kinase-dependent growth cone
      steering.
AB  - Dynamic microtubules explore the peripheral (P) growth cone domain using F actin
      bundles as polymerization guides. Microtubule dynamics are necessary for growth
      cone guidance; however, mechanisms of microtubule reorganization during growth
      cone turning are not well understood. Here, we address these issues by analyzing
      growth cone steering events in vitro, evoked by beads derivatized with the Ig
      superfamily cell adhesion protein apCAM. Pharmacological inhibition of
      microtubule assembly with low doses of taxol or vinblastine resulted in rapid
      clearance of microtubules from the P domain with little effect on central (C)
      axonal microtubules or actin-based motility. Early during target interactions, we
      detected F actin assembly and activated Src, but few microtubules, at apCAM bead
      binding sites. The majority of microtubules extended toward bead targets after F
      actin flow attenuation occurred. Microtubule extension during growth cone
      steering responses was strongly suppressed by dampening microtubule dynamics with
      low doses of taxol or vinblastine. These treatments also inhibited growth cone
      turning responses, as well as focal actin assembly and accumulation of active Src
      at bead binding sites. These results suggest that dynamic microtubules carry
      signals involved in regulating Src-dependent apCAM adhesion complexes involved in
      growth cone steering.

PMID- 15242618
TI  - Polo-like kinase-2 is required for centriole duplication in mammalian cells.
AB  - Centriole duplication initiates at the G1-to-S transition in mammalian cells and
      is completed during the S and G2 phases. The localization of a number of protein
      kinases to the centrosome has revealed the importance of protein phosphorylation
      in controlling the centriole duplication cycle. Here we show that the human Polo
      like kinase 2 (Plk2) is activated near the G1-to-S transition of the cell cycle.
      Endogenous and overexpressed HA-Plk2 localize with centrosomes, and this
      interaction is independent of Plk2 kinase activity. In contrast, the kinase
      activity of Plk2 is required for centriole duplication. Overexpression of a
      kinase-deficient mutant under S-phase arrest blocks centriole duplication.
      Downregulation of endogenous Plk2 with small hairpin RNAs interferes with the
      ability to reduplicate centrioles. Furthermore, centrioles failed to duplicate
      during the cell cycle of human fibroblasts and U2OS cells after overexpression of
      a Plk2 dominant-negative mutant. These results show that Plk2 is a physiological
      centrosomal protein and that its kinase activity is likely to be required for
      centriole duplication near the G1-to-S phase transition.

PMID- 15242619
TI  - Identification of the gene encoding bursicon, an insect neuropeptide responsible
      for cuticle sclerotization and wing spreading.
AB  - To accommodate growth, insects must periodically replace their exoskeletons.
      After shedding the old cuticle, the new soft cuticle must sclerotize.
      Sclerotization has long been known to be controlled by the neuropeptide hormone
      bursicon, but its large size of 30 kDa has frustrated attempts to determine its
      sequence and structure. Using partial sequences obtained from purified cockroach
      bursicon, we identified the Drosophila melanogaster gene CG13419 as a candidate
      bursicon gene. CG13419 encodes a peptide with a predicted final molecular weight
      of 15 kDa, which likely functions as a dimer. This predicted bursicon protein
      belongs to the cystine knot family, which includes vertebrate transforming growth
      factor-beta (TGF-beta) and glycoprotein hormones. Point mutations in the bursicon
      gene cause defects in cuticle sclerotization and wing expansion behavior.
      Bioassays show that these mutants have decreased bursicon bioactivity. In situ
      hybridization and immunocytochemistry revealed that bursicon is co-expressed with
      crustacean cardioactive peptide (CCAP). Transgenic flies that lack CCAP neurons
      also lacked bursicon bioactivity. Our results indicate that CG13419 encodes
      bursicon, the last of the classic set of insect developmental hormones. It is the
      first member of the cystine knot family to have a defined function in
      invertebrates. Mutants show that the spectrum of bursicon actions is broader than
      formerly demonstrated.

PMID- 15242621
TI  - France rethinks research plans.

PMID- 15242620
TI  - Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA methylation triggered by
      inverted repeats.
AB  - In a number of organisms, transgenes containing transcribed inverted repeats
      (IRs) that produce hairpin RNA can trigger RNA-mediated silencing, which is
      associated with 21-24 nucleotide small interfering RNAs (siRNAs). In plants, IR
      driven RNA silencing also causes extensive cytosine methylation of homologous DNA
      in both the transgene "trigger" and any other homologous DNA sequences-
      "targets". Endogenous genomic sequences, including transposable elements and
      repeated elements, are also subject to RNA-mediated silencing. The RNA silencing
      gene ARGONAUTE4 (AGO4) is required for maintenance of DNA methylation at several
      endogenous loci and for the establishment of methylation at the FWA gene. Here,
      we show that mutation of AGO4 substantially reduces the maintenance of DNA
      methylation triggered by IR transgenes, but AGO4 loss-of-function does not block
      the initiation of DNA methylation by IRs. AGO4 primarily affects non-CG
      methylation of the target sequences, while the IR trigger sequences lose
      methylation in all sequence contexts. Finally, we find that AGO4 and the DRM
      methyltransferase genes are required for maintenance of siRNAs at a subset of
      endogenous sequences, but AGO4 is not required for the accumulation of IR-induced
      siRNAs or a number of endogenous siRNAs, suggesting that AGO4 may function
      downstream of siRNA production.

PMID- 15242622
TI  - Stem cell boost.

PMID- 15242623
TI  - Alexander Schier.

PMID- 15242625
TI  - Qualia.

PMID- 15242626
TI  - Neuronal cell types.

PMID- 15242627
TI  - Synchronous replication initiation of the two Vibrio cholerae chromosomes.

PMID- 15242628
TI  - Social behavior: how do fish find their shoal mate?
AB  - Fish form social aggregations called shoals which often consist of fish with
      similar morphologies. Experiments using zebrafish pigment variants demonstrate
      that fish can select shoal mates solely on the basis of their color patterns, and
      that early experience plays a key role in determining these shoaling preferences.

PMID- 15242629
TI  - Prokaryotic development: a new player on the cell cycle circuit.
AB  - A genetic regulatory circuit recently described in the bacterium Caulobacter
      crescentus generates reciprocal oscillations in the abundance of two key
      transcription factors to control landmark events in the cell cycle.

PMID- 15242630
TI  - Epithelium-mesenchyme: a balancing act of RhoGAP and RhoGEF.
AB  - Transitions between epithelium and mesenchyme, in either direction, contribute
      repeatedly to animal development. Three striking papers suggest that distinct
      components with opposite activities, which together form a complex known for its
      role in cytokinesis, control these opposite transitions.

PMID- 15242631
TI  - Evolution: sperm ejection near and far.
AB  - In promiscuous fruit flies, the last male to inseminate a female has a
      fertilising advantage. Recent evidence indicates that this happens because
      females eject previously stored semen after a new copulation, revealing female
      bias in sperm use and the resulting battle of the sexes over fertilisation.

PMID- 15242632
TI  - Evolution: red algal genome affirms a common origin of all plastids.
AB  - Photosynthetic organelles (plastids) come in many forms and were originally
      thought to have multiple origins. The complete genome of the thermophilic red
      alga Cyanidioschizon merolae provides further evidence that all plastids derive
      from a single endosymbiotic event more than 600 million years ago.

PMID- 15242633
TI  - Cognitive neuroscience: acting on numbers.
AB  - The parietal cortex is a central part of the brain's system for representing
      numbers and magnitudes. Activity in the parietal cortex might reflect number
      representation or actions made in response to the numbers.

PMID- 15242634
TI  - Actin cytoskeleton: formins lead the way.
AB  - Formins are eukaryotic proteins that potently influence actin polymerization
      dynamics. Recent evidence strongly suggests that these proteins move processively
      with the elongating barbed ends of actin filaments.

PMID- 15242635
TI  - Visual cortex: the continuing puzzle of area V2.
AB  - Surprisingly little is known about the role of V2 in visual processing. A recent
      study found that the responses of V2 neurons to pairs of angled lines could be
      predicted from their responses to the individual line components. A simple
      analysis shows how these neurons may simply sum the responses from one or more
      orientation selective V1 neurons.

PMID- 15242636
TI  - Bidirectional transport along microtubules.
AB  - Active transport by microtubule motors has a plethora of crucial roles in
      eukaryotic cells. Organelles often move bidirectionally, employing both plus-end
      and minus-end directed motors. Bidirectional motion is widespread and may allow
      dynamic regulation, error correction and the establishment of polarized organelle
      distributions. Emerging evidence suggests that motors for both directions are
      simultaneously present on cellular 'cargo', but that their activity is
      coordinated so that when plus-end motors are active, minus-end motors are not,
      and vice versa. Both the dynein cofactor dynactin and the Klarsicht (Klar)
      protein appear to be important for such coordination. The direction of net
      transport depends on the balance between plus-end directed and minus-end directed
      motion. In several model systems, factors crucial for setting this balance have
      now been identified, setting the stage for a molecular dissection of the
      underlying regulatory mechanisms. These analyses will likely provide insight into
      motor cooperation in general.

PMID- 15242637
TI  - Small RNAs shed some light.
AB  - Small regulatory RNAs can act by pairing with their target messages, targeting
      themselves and the mRNA for degradation; Lenz et al. (this issue of Cell) now
      report that multiple small RNAs are essential regulators of the quorum-sensing
      systems of Vibrio species, including the regulation of virulence in V. cholerae.

PMID- 15242638
TI  - Neddylating the guardian; Mdm2 catalyzed conjugation of Nedd8 to p53.
AB  - The tumor suppressor and transcriptional regulator p53 is perhaps one of the most
      regulated proteins in the cell nucleus and is acted upon by a variety of protein
      kinases, acetylases, ubiqutin ligases and hydrolases, and SUMO-conjugating
      enzymes. Now new work suggests a role for an additional modification-neddylation
      in negative regulation of p53 transcriptional activity.

PMID- 15242639
TI  - Huntington's disease: new paths to pathogenesis.
AB  - Huntington's disease is a progressive autosomal dominant neurodegenerative
      disorder caused by expansion of a CAG repeat coding for polyglutamine in the
      huntingtin protein. A recent report suggests a new mechanism involving altered
      interactions with a protein involved in axonal transport, leading to loss of
      neurotrophic factor transport. This suggests an intriguing convergence to
      previously described pathways implicating neurotrophin transcription in HD
      pathogenesis.

PMID- 15242640
TI  - Initiating cellular stress responses.
AB  - The phosphoinositide 3-kinase related kinases (PIKKs) mediate responses to
      diverse stresses, including DNA double-strand breaks (DSBs), abnormal replication
      fork progression, the recognition of premature termination codons in mRNAs, and
      inadequate nutrient availability. Rigorous control of these kinases limits
      cellular damage and promotes cell viability in the presence of stress. Control
      mechanisms include the localization of PIKKs into multiprotein complexes at the
      sites of damage and mediation of protein-protein contacts such that substrates
      are allowed access to the PIKK catalytic domains.

PMID- 15242641
TI  - Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b
      cells contributes to the allelic exclusion of light-chain expression.
AB  - Regulated gene rearrangement is thought to underlie allelic exclusion, the
      observation that an individual B cell expresses only a single immunoglobulin
      molecule. Previous data has implicated transcriptional activation of rearranging
      loci in the regulation of their accessibility to the V(D)J recombinase. Using
      homologous recombination in ES cells, we have generated "knockin" mice which
      express a GFP cDNA from an unrearranged immunoglobulin kappa light-chain allele.
      Surprisingly, we find that only a small fraction of kappa alleles are highly
      transcribed in a population of pre-B cells, that such transcription is
      monoallelic, and that these highly transcribed alleles account for the vast
      majority of kappa light-chain gene rearrangement. These data lead us to suggest
      that probabilistic enhancer activation and allelic competition are part of the
      mechanism of kappa locus allelic exclusion and may be a general mechanism
      contributing to cellular differentiation during development.

PMID- 15242642
TI  - Exploration of essential gene functions via titratable promoter alleles.
AB  - Nearly 20% of yeast genes are required for viability, hindering genetic analysis
      with knockouts. We created promoter-shutoff strains for over two-thirds of all
      essential yeast genes and subjected them to morphological analysis, size
      profiling, drug sensitivity screening, and microarray expression profiling. We
      then used this compendium of data to ask which phenotypic features characterized
      different functional classes and used these to infer potential functions for
      uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1,
      URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA
      charging (GSN1). In addition, apparent negative feedback transcriptional
      regulation of both ribosome biogenesis and the proteasome was observed. We
      furthermore show that these strains are compatible with automated genetic
      analysis. This study underscores the importance of analyzing mutant phenotypes
      and provides a resource to complement the yeast knockout collection.

PMID- 15242643
TI  - Maintaining the ribosomal reading frame: the influence of the E site during
      translational regulation of release factor 2.
AB  - Maintenance of the translation reading frame is one of the most remarkable
      achievements of the ribosome while decoding the information of an mRNA. Loss of
      the reading frame through spontaneous frameshifting occurs with a frequency of
      one in 30,000 amino acid incorporations. However, at many recoding sites, the
      mechanism that controls reading frame maintenance is switched off. One such
      example is the programmed +1 frameshift site of the prfB gene encoding the
      termination factor RF2, in which slippage into the forward frame by one
      nucleotide can attain an efficiency of approximately 100%, namely, four orders of
      magnitude higher than normally observed. Here, using the RF2 frameshift window,
      we demonstrate that premature release of the E site tRNA from the ribosome is
      coupled with high-level frameshifting. Consistently, in a minimal system, the
      presence of the E site tRNA prevents the +1 frameshift event, illustrating the
      importance of the E site for reading-frame maintenance.

PMID- 15242644
TI  - Single processing center models for human Dicer and bacterial RNase III.
AB  - Dicer is a multidomain ribonuclease that processes double-stranded RNAs (dsRNAs)
      to 21 nt small interfering RNAs (siRNAs) during RNA interference, and excises
      microRNAs from precursor hairpins. Dicer contains two domains related to the
      bacterial dsRNA-specific endonuclease, RNase III, which is known to function as a
      homodimer. Based on an X-ray structure of the Aquifex aeolicus RNase III, models
      of the enzyme interaction with dsRNA, and its cleavage at two composite catalytic
      centers, have been proposed. We have generated mutations in human Dicer and
      Escherichia coli RNase III residues implicated in the catalysis, and studied
      their effect on RNA processing. Our results indicate that both enzymes have only
      one processing center, containing two RNA cleavage sites and generating products
      with 2 nt 3' overhangs. Based on these and other data, we propose that Dicer
      functions through intramolecular dimerization of its two RNase III domains,
      assisted by the flanking RNA binding domains, PAZ and dsRBD.

PMID- 15242645
TI  - The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in
      Vibrio harveyi and Vibrio cholerae.
AB  - Quorum-sensing bacteria communicate with extracellular signal molecules called
      autoinducers. This process allows community-wide synchronization of gene
      expression. A screen for additional components of the Vibrio harveyi and Vibrio
      cholerae quorum-sensing circuits revealed the protein Hfq. Hfq mediates
      interactions between small, regulatory RNAs (sRNAs) and specific messenger RNA
      (mRNA) targets. These interactions typically alter the stability of the target
      transcripts. We show that Hfq mediates the destabilization of the mRNA encoding
      the quorum-sensing master regulators LuxR (V. harveyi) and HapR (V. cholerae),
      implicating an sRNA in the circuit. Using a bioinformatics approach to identify
      putative sRNAs, we identified four candidate sRNAs in V. cholerae. The
      simultaneous deletion of all four sRNAs is required to stabilize hapR mRNA. We
      propose that Hfq, together with these sRNAs, creates an ultrasensitive regulatory
      switch that controls the critical transition into the high cell density, quorum
      sensing mode.

PMID- 15242646
TI  - Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity.
AB  - The only reported role for the conjugation of the NEDD8 ubiquitin-like molecule
      is control of the activity of SCF ubiquitin ligase complexes. Here, we show that
      the Mdm2 RING finger E3 ubiquitin ligase can also promote NEDD8 modification of
      the p53 tumor suppressor protein. Mdm2 is itself modified with NEDD8 with very
      similar characteristics to the autoubiquitination activity of Mdm2. By using a
      cell line (TS-41) with a temperature-sensitive mutation in the NEDD8 conjugation
      pathway and a p53 mutant that cannot be NEDDylated (3NKR), we demonstrate that
      Mdm2-dependent NEDD8 modification of p53 inhibits its transcriptional activity.
      These findings expand the role for Mdm2 as an E3 ligase, providing evidence that
      Mdm2 is a common component of the ubiquitin and NEDD8 conjugation pathway and
      indicating the diverse mechanisms by which E3 ligases can control the function of
      substrate proteins.

PMID- 15242647
TI  - Multiubiquitin chain receptors define a layer of substrate selectivity in the
      ubiquitin-proteasome system.
AB  - Recruitment of ubiquitinated proteins to the 26S proteasome lies at the heart of
      the ubiquitin-proteasome system (UPS). Genetic studies suggest a role for the
      multiubiquitin chain binding proteins (MCBPs) Rad23 and Rpn10 in recruitment, but
      biochemical studies implicate the Rpt5 ATPase. We addressed this issue by
      analyzing degradation of the ubiquitinated Cdk inhibitor Sic1 (UbSic1) in vitro.
      Mutant rpn10Delta and rad23Delta proteasomes failed to bind or degrade UbSic1.
      Although Rpn10 or Rad23 restored UbSic1 recruitment to either mutant, rescue of
      degradation by Rad23 uncovered a requirement for the VWA domain of Rpn10. In vivo
      analyses confirmed that Rad23 and the multiubiquitin binding domain of Rpn10
      contribute to Sic1 degradation. Turnover studies of multiple UPS substrates
      uncovered an unexpected degree of specificity in their requirements for MCBPs. We
      propose that recruitment of substrates to the proteasome by MCBPs provides an
      additional layer of substrate selectivity in the UPS.

PMID- 15242648
TI  - A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell
      migration.
AB  - Border cell migration in the Drosophila ovary is a relatively simple and
      genetically tractable model for studying the conversion of epithelial cells to
      migratory cells. Like many cell migrations, border cell migration is inhibited by
      a dominant-negative form of the GTPase Rac. To identify new genes that function
      in Rac-dependent cell motility, we screened for genes that when overexpressed
      suppressed the migration defect caused by dominant-negative Rac. Overexpression
      of the Drosophila inhibitor of apoptosis 1 (DIAP1), which is encoded by the
      thread (th) gene, suppressed the migration defect. Moreover, loss-of-function
      mutations in th caused migration defects but, surprisingly, did not cause
      apoptosis. Mutations affecting the Dark protein, an activator of the upstream
      caspase Dronc, also rescued RacN17 migration defects. These results indicate an
      apoptosis-independent role for DIAP1-mediated Dronc inhibition in Rac-mediated
      cell motility.

PMID- 15242649
TI  - Huntingtin controls neurotrophic support and survival of neurons by enhancing
      BDNF vesicular transport along microtubules.
AB  - Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and
      responsible for the neuronal toxicity associated with Huntington's disease (HD).
      Although wild-type huntingtin possesses antiapoptotic properties, the
      relationship between the neuroprotective functions of huntingtin and pathogenesis
      of HD remains unclear. Here, we show that huntingtin specifically enhances
      vesicular transport of brain-derived neurotrophic factor (BDNF) along
      microtubules. Huntingtin-mediated transport involves huntingtin-associated
      protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component
      of molecular motors. BDNF transport is attenuated both in the disease context and
      by reducing the levels of wild-type huntingtin. The alteration of the
      huntingtin/HAP1/p150(Glued) complex correlates with reduced association of motor
      proteins with microtubules. Finally, we find that the polyQ-huntingtin-induced
      transport deficit results in the loss of neurotrophic support and neuronal
      toxicity. Our findings indicate that a key role of huntingtin is to promote BDNF
      transport and suggest that loss of this function might contribute to
      pathogenesis.

PMID- 15242650
TI  - Neuroscience and computation.

PMID- 15242651
TI  - Homeostatic plasticity in the CNS: synaptic and intrinsic forms.
AB  - The study of experience-dependent plasticity has been dominated by questions of
      how Hebbian plasticity mechanisms act during learning and development. This is
      unsurprising as Hebbian plasticity constitutes the most fully developed and
      influential model of how information is stored in neural circuits and how neural
      circuitry can develop without extensive genetic instructions. Yet Hebbian
      plasticity may not be sufficient for understanding either learning or
      development: the dramatic changes in synapse number and strength that can be
      produced by this kind of plasticity tend to threaten the stability of neural
      circuits. Recent work has suggested that, in addition to Hebbian plasticity,
      homeostatic regulatory mechanisms are active in a variety of preparations. These
      mechanisms alter both the synaptic connections between neurons and the intrinsic
      electrical properties of individual neurons, in such a way as to maintain some
      constancy in neuronal properties despite the changes wrought by Hebbian
      mechanisms. Here we review the evidence for homeostatic plasticity in the central
      nervous system, with special emphasis on results from cortical preparations.

PMID- 15242652
TI  - Brain plasticity and ion channels.
AB  - It is generally believed that spatio-temporal configurations of distributed
      activity in the brain contribute to the coding of neuronal information and that
      synaptic contacts between nerve cells could play a central role in the formation
      of privileged pathways of activity. Synaptic plasticity is not the only mode of
      regulation of information processing in the brain and persistent regulations of
      ionic conductances in some specialized neuronal areas such as the dendrites, the
      cell body and the axon could also modulate, in the short- and the long-term, the
      propagation of information in the brain. Persistent changes in intrinsic
      excitability have been reported in several brain areas in which activity is
      modified during a classical conditioning. The role of synaptic activity seems to
      be determinant in the induction but the learning rules and the underlying
      mechanisms remain to be defined. This review discusses the role of neuronal
      activity in the induction of intrinsic plasticity in cortical, hippocampal and
      cerebellar neurons. Activation and inactivation properties of ionic channels in
      the axon determine the short-term dynamics of axonal propagation and synaptic
      transmission. Activation of glutamate receptors initiates a long-term
      modification in neuronal excitability that may represent the substrate for the
      mnesic engram and for the stabilization of the epileptic state. Similarly to
      synaptic plasticity, long-lasting intrinsic plasticity appears to be reversible
      and to express a certain level of input or cellular specificity. These non
      synaptic forms of plasticity affect the signal propagation in the axon, the
      dendrites and the soma. They not only share common learning rules and induction
      pathways with the better known synaptic plasticity such as NMDA receptor
      dependent LTP and LTD but also contribute in synergy with these synaptic changes
      to the formation of a coherent mnesic engram.

PMID- 15242653
TI  - Hippocampal long term potentiation: silent synapses and beyond.
AB  - Long-term, activity-driven synaptic plasticity allows neuronal networks to
      constantly and durably adjust synaptic gains between synaptic partners. These
      processes have been proposed to serve as a substrate for learning and memory.
      Long-term synaptic potentiation (LTP) has been observed at many central
      excitatory synapses and perhaps most extensively studied at Schaffer collaterals
      synapses onto hippocampal CA1 neurons. Multiple contradictory models were
      proposed to account for this form of LTP. However, recent evidence suggests that
      some synapses are initially devoid of functional AMPA receptors which can be
      incorporated during LTP. This new model appears to account for most, but not all,
      properties of this form of plasticity. Indeed, several mechanisms seem to act in
      parallel to specifically enhance AMPA-receptor mediated synaptic transmission.

PMID- 15242654
TI  - Prefrontal cortex function, quasi-physiological stimuli, and synaptic plasticity.
AB  - The prelimbic area of rat medial frontal cortex may be functionally analogous to
      human/primate dorsolateral prefrontal cortex. This area may be involved in
      selective attention to the external stimuli and the coupling of the attention to
      a repertory of actions. It was suggested that this function may rely on a form of
      long-term memory [Biol. Rev. 77 (2002) 563]. Indeed, during learning of this type
      of behavior, a portion of prelimbic neurons persistently change their firing
      characteristics [Prog. Brain Res. 126 (2000) 287]. It is therefore important to
      study long-term potentiation (LTP) and depression (LTD) in rat prelimbic neurons.
      In this article, the author first briefly reviews recent findings on the
      prefrontal cortex function and discusses that the prefrontal cortex may be
      involved in long-term memory. Second, the author will show some new results which
      indicate that quasi-physiological patterns of stimuli mimicking prelimbic
      neuronal activity during behavior can induce LTP in prelimbic pyramidal neuron
      synapses. These results suggest that prelimbic neuronal activity during behavior
      may lastingly modify prelimbic synaptic efficacy.

PMID- 15242655
TI  - Acetylcholine-dependent potentiation of temporal frequency representation in the
      barrel cortex does not depend on response magnitude during conditioning.
AB  - The response properties of neurons of the postero-medial barrel sub-field of the
      somatosensory cortex (the cortical structure receiving information from the
      mystacial vibrissae can be modified as a consequence of peripheral manipulations
      of the afferent activity. This plasticity depends on the integrity of the
      cortical cholinergic innervation, which originates at the nucleus basalis
      magnocellularis (NBM). The activity of the NBM is related to the behavioral state
      of the animal and the putative cholinergic neurons are activated by specific
      events, such as reward-related signals, during behavioral learning. Experimental
      studies on acetylcholine (ACh)-dependent cortical plasticity have shown that ACh
      is needed for both the induction and the expression of plastic modifications
      induced by sensory-cholinergic pairings. Here we review and discuss ACh-dependent
      plasticity and activity-dependent plasticity and ask whether these two mechanisms
      are linked. To address this question, we analyzed our data and tested whether
      changes mediated by ACh were activity-dependent. We show that ACh-dependent
      potentiation of response in the barrel cortex of rats observed after sensory
      cholinergic pairing was not correlated to the changes in activity induced during
      pairing. Since these results suggest that the effect of ACh during pairing is not
      exerted through a direct control of the post-synaptic activity, we propose that
      ACh might induce its effect either pre- or post-synaptically through activation
      of second messenger cascades.

PMID- 15242656
TI  - Shunting inhibition, a silent step in visual cortical computation.
AB  - Brain computation, in the early visual system, is often considered as a
      hierarchical process in which features extracted in a given sensory relay are not
      present in previous stages of integration. In particular, orientation preference
      and its fine tuning selectivity are functional properties shared by most cortical
      cells and they are not observed at the preceding geniculate stage. A classical
      problem is identifying the mechanisms and circuitry underlying these
      computations. Several organizational principles have been proposed, giving
      different weights to the feedforward thalamocortical drive or to intracortical
      recurrent architectures. Within this context, an important issue is whether
      intracortical inhibition is fundamental for the genesis of stimulus selectivity,
      or rather normalizes spike response tuning with respect to other features such as
      stimulus strength or contrast, without influencing the selectivity bias and
      preference expressed in the excitatory input alone. We review here experimental
      observations concerning the presence or absence of inhibitory input evoked by non
      preferred orientation/directions. Intracellular current clamp and voltage clamp
      recordings are analyzed in the light of new methods allowing us (1) to increase
      the visibility of inhibitory input, and (2) to continuously measure the visually
      evoked dynamics of input conductances. We conclude that there exists a diversity
      of synaptic input combinations generating the same profile of spike-based
      orientation selectivity, and that this diversity most likely reflects anatomical
      non-homogeneities in input sampling provided by the local context of the columnar
      and lateral intracortical network in which the considered cortical cell is
      embedded.

PMID- 15242657
TI  - The "silent" surround of V1 receptive fields: theory and experiments.
AB  - The spiking response of a primary visual cortical cell to a stimulus placed
      within its receptive field can be up- and down-regulated by the simultaneous
      presentation of objects or scenes placed in the "silent" regions which surround
      the receptive field. We here review recent progresses that have been made both at
      the experimental and theoretical levels in the description of these so-called
      "Center/Surround" modulations and in the understanding of their neural basis.
      Without denying the role of a modulatory feedback from higher cortical areas,
      recent results support the view that some of these phenomena result from the
      dynamic interplay between feedforward projections and horizontal intracortical
      connectivity in V1. Uncovering the functional role of the contextual periphery of
      cortical receptive fields has become an area of active investigation. The
      detailed comparison of electrophysiological and psychophysical data reveals
      strong correlations between the integrative behavior of V1 cells and some aspects
      of "low-level" and "mid-level" conscious perception. These suggest that as early
      as the V1 stage, the visual system is able to make use of contextual cues to
      recover local visual scene properties or correct their interpretation. Promising
      ideas have emerged on the importance of such a strategy for the coding of visual
      scenes, and the processing of static and moving objects.

PMID- 15242658
TI  - Pattern formation and cortical maps.
AB  - The response selectivities of neurons in adult primary sensory cortices depend on
      intricate patterns of synaptic connections; these selectivities are arranged over
      cortex in equally rich fashion. Characterising these patterns, and particularly
      the activity-dependence (and independence) of their developmental trajectories,
      has been a major task for experimental and theoretical neuroscience. Here, we
      describe and analyse a paradigmatic algorithm for activity-dependent development
      of the refinement and generation of neuronal selectivities, and relate it to some
      of the wealth of suggestions in the literature.

PMID- 15242659
TI  - Role of statistical symmetries in sensory coding: an optimal scale invariant code
      for vision.
AB  - The visual system is the most studied sensory pathway, which is partly because
      visual stimuli have rather intuitive properties. There are reasons to think that
      the underlying principle ruling coding, however, is the same for vision and any
      other type of sensory signal, namely the code has to satisfy some notion of
      optimality--understood as minimum redundancy or as maximum transmitted
      information. Given the huge variability of natural stimuli, it would seem that
      attaining an optimal code is almost impossible; however, regularities and
      symmetries in the stimuli can be used to simplify the task: symmetries allow
      predicting one part of a stimulus from another, that is, they imply a structured
      type of redundancy. Optimal coding can only be achieved once the intrinsic
      symmetries of natural scenes are understood and used to the best performance of
      the neural encoder. In this paper, we review the concepts of optimal coding and
      discuss the known redundancies and symmetries that visual scenes have. We discuss
      in depth the only approach which implements the three of them known so far:
      translational invariance, scale invariance and multiscaling. Not surprisingly,
      the resulting code possesses features observed in real visual systems in mammals.

PMID- 15242660
TI  - V1 mechanisms and some figure-ground and border effects.
AB  - V1 neurons have been observed to respond more strongly to figure than background
      regions. Within a figure region, the responses are usually stronger near figure
      boundaries (the border effect), than further inside the boundaries. Sometimes the
      medial axes of the figures (e.g., the vertical midline of a vertical figure
      strip) induce secondary, intermediate, response peaks (the medial axis effect).
      Related is the physiologically elusive "cross-orientation facilitation", the
      observation that a cell's response to a grating patch can be facilitated by an
      orthogonally oriented grating in the surround. Higher center feedbacks have been
      suggested to cause these figure-ground effects. It has been shown, using a V1
      model, that the causes could be intra-cortical interactions within V1 that serve
      pre-attentive visual segmentation, particularly, object boundary detection.
      Furthermore, whereas the border effect is robust, the figure-ground effects in
      the interior of a figure, in particular, the medial axis effect, are by-products
      of the border effect and are predicted to diminish to zero for larger figures.
      This model prediction (of the figure size dependence) was subsequently confirmed
      physiologically, and supported by findings that the response modulations by
      texture surround do not depend on feedbacks from V2. In addition, the model
      explains the "cross-orientation facilitation" as caused by a dis-inhibition, to
      the cell responding to the center of the central grating, by the background
      grating. Furthermore, the elusiveness of this phenomena was accounted for by the
      insight that it depends critically on the size of the figure grating. The model
      is applied to understand some figure-ground effects and segmentation in
      psychophysics: in particular, that contrast discrimination threshold is lower
      within and at the center of a closed contour than that in the background, and
      that a very briefly presented vernier target can perceptually shine through a
      subsequently presented large grating centered at the same location.

PMID- 15242661
TI  - Local neurons play key roles in the mammalian olfactory bulb.
AB  - Over the past few decades, research exploring how the brain perceives,
      discriminates, and recognizes odorant molecules has received a growing interest.
      Today, olfaction is no longer considered a matter of poetry. Chemical senses
      entered the biological era when an increasing number of scientists started to
      elucidate the early stages of the olfactory pathway. A combination of genetic,
      biochemical, cellular, electrophysiological and behavioral methods has provided a
      picture of how odor information is processed in the olfactory system as it moves
      from the periphery to higher areas of the brain. Our group is exploring the
      physiology of the main olfactory bulb, the first processing relay in the
      mammalian brain. From different electrophysiological approaches, we are
      attempting to understand the cellular rules that contribute to the synaptic
      transmission and plasticity at this central relay. How olfactory sensory inputs,
      originating from the olfactory epithelium located in the nasal cavity, are
      encoded in the main olfactory bulb remains a crucial question for understanding
      odor processing. More importantly, the persistence of a high level of
      neurogenesis continuously supplying the adult olfactory bulb with newborn local
      neurons provides an attractive model to investigate how basic olfactory functions
      are maintained when a large proportion of local neurons are continuously renewed.
      For this purpose, we summarize the current ideas concerning the molecular
      mechanisms and organizational strategies used by the olfactory system to encode
      and process information in the main olfactory bulb. We discuss the degree of
      sensitivity of the bulbar neuronal network activity to the persistence of this
      high level of neurogenesis that is modulated by sensory experience. Finally, it
      is worth mentioning that analyzing the molecular mechanisms and organizational
      strategies used by the olfactory system to transduce, encode, and process odorant
      information in the olfactory bulb should aid in understanding the general neural
      mechanisms involved in both sensory perception and memory. Due to space
      constraints, this review focuses exclusively on the olfactory systems of
      vertebrates and primarily those of mammals.

PMID- 15242662
TI  - Investigations into the organization of information in sensory cortex.
AB  - One might take the exploration of sensory cortex in the first decades of the last
      century as the opening chapter of modern neuroscience. The combined approaches of
      (i) measuring effects of restricted ablation on functional capacities, both in
      the clinic and the laboratory, together with (ii) anatomical investigations of
      cortical lamination, arealization, and connectivity, and (iii) the early
      physiological probing of sensory representations, led to a fundamental body of
      knowledge that remains relevant to this day. In our time, there can be little
      doubt that its organization as a mosaic of columnar modules is the pervasive
      functional property of mammalian sensory cortex [Brain 120 (1997) 701]. If one
      accepts the assertion that columns and maps must improve the functioning of the
      brain (why else would they be the very hallmark of neocortex?), then the
      inevitable question is: exactly what advantages do they permit? In this review of
      our recent presentation at the workshop on Homeostasis, plasticity and learning
      at the Institut Henri Poincare, we will outline a systematic approach to
      investigating the role of modular, map-like cortical organization in the
      processing of sensory information. We survey current evidence concerning the
      functional significance of cortical maps and modules, arguing that sensory cortex
      is involved not solely in the online processing of afferent data, but also in the
      storage and retrieval of information. We also show that the topographic framework
      of primary sensory cortex renders the encoding of sensory information efficient,
      fast and reliable.

PMID- 15242663
TI  - Place cells, neocortex and spatial navigation: a short review.
AB  - Hippocampal place cells are characterized by location-specific firing, that is
      each cell fires in a restricted region of the environment explored by the rat. In
      this review, we briefly examine the sensory information used by place cells to
      anchor their firing fields in space and show that, among the various sensory cues
      that can influence place cell activity, visual and motion-related cues are the
      most relevant. We then explore the contribution of several cortical areas to the
      generation of the place cell signal with an emphasis on the role of the visual
      cortex and parietal cortex. Finally, we address the functional significance of
      place cell activity and demonstrate the existence of a clear relationship between
      place cell positional activity and spatial navigation performance. We conclude
      that place cells, together with head direction cells, provide information useful
      for spatially guided movements, and thus provide a unique model of how spatial
      information is encoded in the brain.

PMID- 15242664
TI  - Persistent activity in limbic system neurons: neurophysiological and modeling
      perspectives.
AB  - Neural activity persisting for one to hundreds of seconds has been postulated to
      be a substrate of memory. This review article illustrates examples of such
      activity in limbic system structures including the hippocampus, postsubiculum,
      and the anterodorsal thalamus. These neuronal responses include better known
      correlates with the spatial position as well as with head direction of the animal
      relative to its environment as well as other lesser known examples. Since head
      direction responses are greater when the animal is actively moving than when
      passively rotated, it has been proposed that there might be a general mechanism
      where the behavioral state of the animal can provide modulatory gating of such
      persistent signals. This would regulate the relative influence of these signals
      on downstream structures. Neural network attractor models of the head direction
      cell system are presented to demonstrate how these responses might originate, as
      well as the dynamics by which they are updated during movements.

PMID- 15242665
TI  - Various synaptic activities and firing patterns in cortico-striatal and striatal
      neurons in vivo.
AB  - It is commonly assumed that spontaneous activity of striatal output neurons is
      characterized by a two-state behavior. This assumption is mainly based on in vivo
      intracellular recordings under urethane and/or ketamine-xylazine anesthesia
      showing that striatal neurons oscillate between two preferred membrane
      potentials, a Down state (hyperpolarized level), resulting from an inwardly
      rectifying potassium conductance, and an Up state (depolarized level) caused by
      complex interactions between a barrage of cortical synaptic excitation and
      voltage-dependent potassium conductances. However, a recent comparative study
      using different anesthetics showed that striatal neurons can exhibit various
      shapes of synaptic activity depending on the temporal structure and the degree of
      synchronization of their cortico-striatal afferents. These new data demonstrate
      that the "classical" Up and Down states do not provide the unique spontaneous
      activity that can be encountered in striatal neurons in vivo. Rather we propose
      that striatal neurons should exhibit various synaptic activities and firing
      patterns depending on the states of vigilance. This hypothesis would be validated
      in further experiments in which the intracellular activity of striatal neurons
      will be recorded during the natural sleep-wake cycle.

PMID- 15242666
TI  - Conditional visuo-motor learning in primates: a key role for the basal ganglia.
AB  - Sensory guidance of behavior often involves standard visuo-motor mapping of body
      movements onto objects and spatial locations. For example, looking at and
      reaching to grasp a glass of wine requires the mapping of the eyes and hand to
      the location of the glass in space, as well as the formation of a hand
      configuration appropriate to the shape of the glass. But our brain is far more
      than just a standard sensorimotor mapping machine. Through evolution, the brain
      of advanced mammals, in particular human and non-human primates, has acquired a
      formidable capacity to construct non-standard, arbitrary mapping using
      associations between external events and behavioral responses that bear no direct
      relationship. For example, we have all learned to stop at a red traffic light and
      to go at a green one, or to wait for a specific tone before dialing a phone
      number and to hang up when hearing a busy signal. These arbitrary associations
      are acquired through experience, thereby providing primates with a rich and
      flexible sensorimotor repertoire. Understanding how they are learned, and how
      they are recalled and used when the context requires them, has been one of the
      challenging issues for cognitive neuroscience. Valuable insights have been gained
      over the last two decades through the convergence of multiple complementary
      approaches. Human neuropsychology and experimental lesions in monkeys have
      identified a network of brain structures important for conditional sensorimotor
      associations, whereas imaging studies in healthy human subjects and
      electrophysiological recordings in awake monkeys have sought to identify the
      different functional processes underlying the overall function. The present
      review focuses on the contribution of a network linking the prefrontal cortex,
      basal ganglia, and dorsal premotor cortex, with special emphasis on results from
      recording experiments in monkeys. We will first review data pointing to a
      specific contribution of each component of the network to the performance of well
      learned arbitrary visuo-motor associations, as well as data suggesting how novel
      associations are formed. Then we will propose a model positing that each
      component of the fronto-striatal network makes a specific contribution to the
      formation and/or execution of sensorimotor associations. In this model, the basal
      ganglia are thought to play a key role in linking the sensory, motor, and reward
      information necessary for arbitrary mapping.

PMID- 15242667
TI  - Anatomical funneling, sparse connectivity and redundancy reduction in the neural
      networks of the basal ganglia.
AB  - The major anatomical characteristics of the main axis of the basal ganglia are:
      (1) Numerical reduction in the number of neurons across layers of the feed
      forward network, (2) lateral inhibitory connections within the layers, and (3)
      neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia
      neurons and on the efficacy of information transmission along the basal ganglia
      axis. We recorded the simultaneous activity of neurons in the output stages of
      the basal ganglia as well as the activity of dopaminergic and cholinergic neurons
      during the performance of a probability decision-making task. We found that the
      functional messages of the cholinergic and dopaminergic neurons differ, and that
      the cholinergic message is less specific than that of the dopaminergic neurons.
      The output stage of the basal ganglia showed uncorrelated neuronal activity. We
      conclude that despite the huge numerical reduction from the cortex to the output
      nuclei of the basal ganglia, the activity of these nuclei represents an optimally
      compressed (uncorrelated) version of distinctive features of cortical
      information.

PMID- 15242668
TI  - Detection of sequences in the cerebellar cortex: numerical estimate of the
      possible number of tidal-wave inducing sequences represented.
AB  - The two major cortices of the brain--the cerebral and cerebellar cortex--are
      massively connected through intercalated nuclei (pontine, cerebellar and thalamic
      nuclei). We suggest that the two cortices co-operate by generating precise
      temporal patterns in the cerebral cortex that are detected in the cerebellar
      cortex as temporal patterns assembled spatially in the mossy fibers. We will
      begin by showing that the tidal-wave mechanism works in the cerebellar cortex as
      a read-out mechanism for such spatio-temporal patterns due to the synchronous
      activity they generate in the parallel fiber system which drives the Purkinje
      cells--the output neurons of the cerebellar cortex--to fire action potentials. We
      will review the anatomy of the mossy fibers and show that within a "beam", or
      "row" of cerebellar cortex the mossy fibers in principle could embed a vast
      number of tidal-wave generating sequences. Based on anatomical data we will argue
      that the cerebellar mossy fiber-granule cell-Purkinje cell system can potentially
      detect and--through learning--select from an enormous number of spatio-temporal
      patterns.

PMID- 15242669
TI  - Recurrent neural networks of integrate-and-fire cells simulating short-term
      memory and wrist movement tasks derived from continuous dynamic networks.
AB  - Dynamic recurrent neural networks composed of units with continuous activation
      functions provide a powerful tool for simulating a wide range of behaviors, since
      the requisite interconnections can be readily derived by gradient descent
      methods. However, it is not clear whether more realistic integrate-and-fire cells
      with comparable connection weights would perform the same functions. We therefore
      investigated methods to convert dynamic recurrent neural networks of continuous
      units into networks with integrate-and-fire cells. The transforms were tested on
      two recurrent networks derived by backpropagation. The first simulates a short
      term memory task with units that mimic neural activity observed in cortex of
      monkeys performing instructed delay tasks. The network utilizes recurrent
      connections to generate sustained activity that codes the remembered value of a
      transient cue. The second network simulates patterns of neural activity observed
      in monkeys performing a step-tracking task with flexion/extension wrist
      movements. This more complicated network provides a working model of the
      interactions between multiple spinal and supraspinal centers controlling
      motoneurons. Our conversion algorithm replaced each continuous unit with multiple
      integrate-and-fire cells that interact through delayed "synaptic potentials".
      Successful transformation depends on obtaining an appropriate fit between the
      activation function of the continuous units and the input-output relation of the
      spiking cells. This fit can be achieved by adapting the parameters of the
      synaptic potentials to replicate the input-output behavior of a standard
      sigmoidal activation function (shown for the short-term memory network).
      Alternatively, a customized activation function can be derived from the input
      output relation of the spiking cells for a chosen set of parameters (demonstrated
      for the wrist flexion/extension network). In both cases the resulting networks of
      spiking cells exhibited activity that replicated the activity of corresponding
      continuous units. This confirms that the network solutions obtained through
      backpropagation apply to spiking networks and provides a useful method for
      deriving recurrent spiking networks performing a wide range of functions.

PMID- 15242670
TI  - Intracranial EEG and human brain mapping.
AB  - This review is an attempt to highlight the value of human intracranial recordings
      (intracranial electro-encephalography, iEEG) for human brain mapping, based on
      their technical characteristics and based on the corpus of results they have
      already yielded. The advantages and limitations of iEEG recordings are introduced
      in detail, with an estimation of their spatial and temporal resolution for both
      monopolar and bipolar recordings. The contribution of iEEG studies to the general
      field of human brain mapping is discussed through a review of the effects
      observed in the iEEG while patients perform cognitive tasks. Those effects range
      from the generation of well-localized evoked potentials to the formation of large
      scale interactions between distributed brain structures, via long-range synchrony
      in particular. A framework is introduced to organize those iEEG studies according
      to the level of complexity of the spatio-temporal patterns of neural activity
      found to correlate with cognition. This review emphasizes the value of iEEG for
      the study of large-scale interactions, and describes in detail the few studies
      that have already addressed this point.

PMID- 15242671
TI  - Exploring the nonlinear dynamics of the brain.
AB  - The growing need for a better understanding of large-scale brain dynamics has
      stimulated in the last decade the development of new and more advanced data
      analysis techniques. Progress in this domain has greatly benefited from
      developments in nonlinear time series analysis. This review gives a short
      overview of some of the nonlinear properties one may wish to infer from brain
      recordings and presents some examples and recent applications.

PMID- 15242672
TI  - Magnetoencephalography and its Achilles' heel.
AB  - Magnetoencephalography (MEG) has practically unlimited temporal resolution.
      Fundamental physical reasons, however, restrict the capability of MEG to separate
      simultaneously active sources. After a brief tutorial introduction into MEG,
      various aspects of spatial resolution are reviewed with the help of examples.
      First the estimation of a single current dipole is examined. A consideration of
      the resolution field shows that the spatial selectivity of the estimated dipole
      moment is highly dependent on methodological issues. A subsequent consideration
      of various two-dipole configurations illustrates how the topography of the
      magnetic field depends on the distance between the two dipoles and their relative
      orientations. The resolution fields associated with the estimation of the dipole
      moments reveal a strong interference for closely spaced dipoles. A simple model
      suggests that the standard deviations of the estimated moments are inversely
      proportional to the distance of the dipoles. Spatial information provided by
      techniques like functional magnetic resonance imaging (fMRI) could help to
      overcome problems resulting from the limited spatial resolution of MEG
      (multimodal integration). But a straightforward synthesis, according to the
      principle that fMRI provides the spatial structure of the sources and MEG adds
      the temporal information, is probably doomed to failure in many situations. A
      serious dilemma, among other problems, is that the fMRI signal generally
      represents a temporal integral over several seconds: The knowledge that a certain
      brain region was active sometime or other is not necessarily helpful for
      disentangling the MEG activity within a specified short time window. An
      intriguing fact is that the spatio-temporal pattern of the MEG signals can be
      considered as a signature of the brain which is suitable for hypothesis testing
      with high temporal and spatial resolution.

PMID- 15242673
TI  - Modelling the formation of working memory with networks of integrate-and-fire
      neurons connected by plastic synapses.
AB  - In this paper we review a series of works concerning models of spiking neurons
      interacting via spike-driven, plastic, Hebbian synapses, meant to implement
      stimulus driven, unsupervised formation of working memory (WM) states. Starting
      from a summary of the experimental evidence emerging from delayed matching to
      sample (DMS) experiments, we briefly review the attractor picture proposed to
      underlie WM states. We then describe a general framework for a theoretical
      approach to learning with synapses subject to realistic constraints and outline
      some general requirements to be met by a mechanism of Hebbian synaptic
      structuring. We argue that a stochastic selection of the synapses to be updated
      allows for optimal memory storage, even if the number of stable synaptic states
      is reduced to the extreme (bistable synapses). A description follows of models of
      spike-driven synapses that implement the stochastic selection by exploiting the
      high irregularity in the pre- and post-synaptic activity. Reasons are listed why
      dynamic learning, that is the process by which the synaptic structure develops
      under the only guidance of neural activities, driven in turn by stimuli, is hard
      to accomplish. We provide a 'feasibility proof' of dynamic formation of WM states
      in this context the beneficial role of short-term depression (STD) is
      illustrated. by showing how an initially unstructured network autonomously
      develops a synaptic structure supporting simultaneously stable spontaneous and WM
      states in this context the beneficial role of short-term depression (STD) is
      illustrated. After summarizing heuristic indications emerging from the study
      performed, we conclude by briefly discussing open problems and critical issues
      still to be clarified.

PMID- 15242675
TI  - Warfarin and the vitamin K-dependent gamma-carboxylation system.
AB  - Insight into the molecular basis for genetic warfarin resistance has recently
      been accomplished by the identification of an 18-kDa protein of the endoplasmic
      reticulum that is targeted by the drug. When expressed in eukaryotic and insect
      cells, the protein reduces vitamin K1 2,3-epoxide in a warfarin-sensitive
      reaction. This finding strongly suggests that the protein is part of the vitamin
      K cycle, which is essential for the production of vitamin K-dependent proteins.
      Identification of the 18-kDa protein has aided the understanding of the vitamin K
      dependent gamma-carboxylation system at the molecular level.

PMID- 15242674
TI  - Optimal computation with attractor networks.
AB  - We investigate the ability of multi-dimensional attractor networks to perform
      reliable computations with noisy population codes. We show that such networks can
      perform computations as reliably as possible--meaning they can reach the Cramer
      Rao bound--so long as the noise is small enough. "Small enough" depends on the
      properties of the noise, especially its correlational structure. For many
      correlational structures, noise in the range of what is observed in the cortex is
      sufficiently small that biologically plausible networks can compute optimally. We
      demonstrate that this result applies to computations that involve cues of varying
      reliability, such as the position of an object on the retina in bright versus dim
      light.

PMID- 15242676
TI  - The thyroglobulin gene: the third locus for autoimmune thyroid disease or a false
      dawn?
AB  - Genetic studies have identified the HLA and CTLA4 regions as susceptibility loci
      for the development of common autoimmune thyroid diseases (AITDs), including
      Graves' disease and autoimmune hypothyroidism. Despite numerous studies, the
      identification of a third locus has remained elusive. Genetic-linkage studies
      have implicated chromosome 8q24 as a susceptibility locus for AITD. The gene
      encoding thyroglobulin (Tg), which encodes a major thyroid autoantigen, maps to
      this region, and a recent study has reported the association of several exonic
      single-nucleotide polymorphisms (SNPs) with disease. Although these preliminary
      data are potentially exciting, caution needs to be exercised, and replication of
      the data sought before Tg can be designated as the third locus for AITD.

PMID- 15242677
TI  - The thyroglobulin gene as the first thyroid-specific susceptibility gene for
      autoimmune thyroid disease.
AB  - Recent linkage and association studies provide evidence for thyroglobulin (Tg)
      being an autoimmune thyroid disease (AITD) susceptibility gene. The Tg locus has
      been reported to be linked with AITD in two independent studies, and further
      analysis demonstrated that markers within the Tg gene were associated with AITD.
      Furthermore, missense single-nucleotide polymorphisms (SNPs) in the Tg gene were
      shown to be associated with autoimmune thyroiditis in both mice and humans. If Tg
      is confirmed as a susceptibility gene for AITD, it could provide a novel
      therapeutic target.

PMID- 15242678
TI  - Stem cells as therapy for hearing loss.
AB  - One of the greatest challenges in the treatment of inner-ear disorders is to find
      a cure for the hearing loss that is caused by the loss of cochlear hair cells or
      spiral ganglion neurons. The recent discovery of stem cells in the adult inner
      ear that are capable of differentiating into hair cells, as well as the finding
      that embryonic stem cells can be converted into hair cells, raise hope for the
      future development of stem-cell-based treatment regimens. Here, we propose
      different approaches for using stem cells to regenerate the damaged inner ear and
      we describe the potential obstacles that translational approaches must overcome
      for the development of stem-cell-based cell-replacement therapies for the damaged
      inner ear.

PMID- 15242679
TI  - Gastric autoimmunity: the role of Helicobacter pylori and molecular mimicry.
AB  - Pathogens can induce autoreactive T cells to initiate autoimmune disease by
      several mechanisms. Pathogen-induced inflammation results in the enhanced
      presentation of self antigens, which causes the expansion of the activated
      autoreactive T cells that are required for disease onset. Alternatively, a
      pathogen might express antigens with epitopes that are structurally similar to
      epitopes of autoantigens, resulting in a mechanism of molecular mimicry. This is
      the case for Helicobacter pylori-associated human autoimmune gastritis, in which
      the activated CD4+ Th1 cells that infiltrate the gastric mucosa cross-recognize
      the epitopes of self gastric parietal cell H(+)K(+)-ATPase and of various H.
      pylori proteins. Therefore, in genetically susceptible individuals, H. pylori
      infection can start or worsen gastric autoimmunity, leading to atrophic
      gastritis.

PMID- 15242680
TI  - Nitric-oxide-donating NSAIDs as agents for cancer prevention.
AB  - Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs), which
      consist of an NSAID with an NO-donating moiety covalently attached to it, promise
      to contribute significantly towards the development of effective chemoprevention
      strategies against cancer. NO-NSAIDs inhibit the growth of cultured cancer cells
      10-6000-fold more potently than their parent NSAIDs and prevent colon cancer in
      animal tumor models. Clinical data indicate that they are extremely safe.
      Mechanistically, NO-aspirin, the best-studied NO-NSAID, has pleiotropic effects
      on cell signaling (it inhibits Wnt signaling, induces nitric oxide synthase and
      NF-kappaB activation and induces cyclooxygenase-2 expression), and this
      mechanistic redundancy might be central to its mode of action against cancer. The
      apparent safety and superior efficacy of NO-NSAIDs makes them promising
      chemopreventive agents against cancer.

PMID- 15242681
TI  - Epstein-Barr virus sustains Burkitt's lymphomas and Hodgkin's disease.
AB  - Two proteins of Epstein-Barr Virus make formerly unrecognized contributions to
      maintaining the tumors of Burkitt's lymphomas and Hodgkin's disease. The Epstein
      Barr nuclear antigen 1 (EBNA1) protein can support the synthesis and maintenance
      of the viral genome. New data show that inhibiting EBNA1 in Burkitt's lymphoma
      cells induces cell death by apoptosis. Therefore, EBNA1 inhibits apoptosis and,
      according to recent findings, does so independently of other viral genes. The
      latent membrane protein 2a (LMP2a) binds to signaling molecules that are engaged
      by the B-cell receptor and inhibits the signaling that is mediated by antigen
      binding. New findings have revealed how LMP2a overcomes the apoptosis that
      normally results from the absence of functional B-cell receptors, and explain how
      Hodgkin's disease tumor cells, which are B cells, survive but lack functional
      antibodies.

PMID- 15242682
TI  - Bisphosphonates: new therapeutic agents for the treatment of bone tumors.
AB  - Bisphosphonates (BPs) have been used successfully for many years to reduce the
      skeletal complications associated with the benign and malignant bone diseases
      that are characterized by enhanced osteoclastic bone resorption. Until recently,
      it was thought that the clinical efficacy of BPs in the treatment of cancer
      patients with bone metastases was purely a result of the inhibition of osteoclast
      mediated bone resorption. However, recent studies have demonstrated that BPs
      inhibit the growth, attachment and invasion of cancer cells in culture and
      promote their apoptosis. These results suggest that BPs are also anti-cancer
      agents, raising the possibility that BPs could inhibit cancer-cell colonization
      in visceral organs. However, results from clinical trials are conflicting, and
      whether BPs possess anti-cancer effects or not remains controversial.

PMID- 15242683
TI  - Functional genetics and experimental models of human cancer.
AB  - Abundant evidence supports the hypothesis that cancer arises from normal cells
      through the stepwise accumulation of genetic mutations. The study of cells
      obtained from patients with cancer has identified numerous molecules and pathways
      that fundamentally contribute to malignant transformation; however, cancer cell
      lines are often difficult to isolate or maintain, and the cell lines that are
      available for experimentation represent only a small subset of late-stage human
      cancers. Recent work has elucidated the role of telomerase in regulating human
      cell lifespan and has enabled the development of new experimental systems to
      study human cancer. This review highlights the recent progress in combining
      genetic methods and primary human cells to understand the role of specific genes
      and pathways in cancer pathogenesis.

PMID- 15242684
TI  - The RET proto-oncogene: a potential target for molecular cancer therapy.
AB  - The inhibition of activated receptor tyrosine kinases has defined a new era of
      selective cancer therapy. The value of these approaches has been demonstrated for
      a growing number of tyrosine kinases. Gain-of-function alterations within the RET
      proto-oncogene are responsible for the development of medullary, as well as
      papillary, thyroid carcinoma and make it a candidate for the design of targeted
      therapies. Recently, various strategies have been used to block the activity of
      RET in pre-clinical models, providing evidence that RET is a potential target for
      a selective cancer-therapy approach, especially when considering that the
      inhibition of RET activity is sufficient to revert neoplastic characteristics.
      Although the ideal clinically useful therapeutic option has yet to be developed,
      successes with other selective tyrosine kinase inhibitors encourages further
      effort.

PMID- 15242685
TI  - Language and conceptual development.

PMID- 15242686
TI  - Monkey homologues of language areas: computing the ambiguities.
AB  - The 'language-readiness' of human brains most probably resulted from modification
      of structures present in non-human primate brains, but identifying such
      homologues and the nature of their modifications has been highly problematic. In
      a recent article, Arbiband Bota suggest that these problems can be overcome using
      a neuroinformatics approach. But its assumptions ignore many non-local, activity
      dependent, regressive, and allometric effects of neurodevelopment that violate
      assumptions of classic homology. What if these effects are what matter most?

PMID- 15242688
TI  - Why rejection hurts: a common neural alarm system for physical and social pain.
AB  - Numerous languages characterize 'social pain', the feelings resulting from social
      estrangement, with words typically reserved for describing physical pain ('broken
      heart', 'broken bones') and perhaps for good reason. It has been suggested that,
      in mammalian species, the social-attachment system borrowed the computations of
      the pain system to prevent the potentially harmful consequences of social
      separation. Mounting evidence from the animal lesion and human neuroimaging
      literatures suggests that physical and social pain overlap in their underlying
      neural circuitry and computational processes. We review evidence suggesting that
      the anterior cingulate cortex plays a key role in the physical-social pain
      overlap. We also suggest that the physical-social pain circuitry might share
      components of a broader neural alarm system.

PMID- 15242689
TI  - An alternative view of the mental lexicon.
AB  - An essential aspect of knowing language is knowing the words of that language.
      This knowledge is usually thought to reside in the mental lexicon, a kind of
      dictionary that contains information regarding a word's meaning, pronunciation,
      syntactic characteristics, and so on. In this article, a very different view is
      presented. In this view, words are understood as stimuli that operate directly on
      mental states. The phonological, syntactic and semantic properties of a word are
      revealed by the effects it has on those states.

PMID- 15242690
TI  - Core systems of number.
AB  - What representations underlie the ability to think and reason about number?
      Whereas certain numerical concepts, such as the real numbers, are only ever
      represented by a subset of human adults, other numerical abilities are widespread
      and can be observed in adults, infants and other animal species. We review recent
      behavioral and neuropsychological evidence that these ontogenetically and
      phylogenetically shared abilities rest on two core systems for representing
      number. Performance signatures common across development and across species
      implicate one system for representing large, approximate numerical magnitudes,
      and a second system for the precise representation of small numbers of individual
      objects. These systems account for our basic numerical intuitions, and serve as
      the foundation for the more sophisticated numerical concepts that are uniquely
      human.

PMID- 15242691
TI  - Comparative mapping of higher visual areas in monkeys and humans.
AB  - The advent of functional magnetic resonance imaging (fMRI) in non-human primates
      has facilitated comparison of the neurobiology of cognitive functions in humans
      and macaque monkeys, the most intensively studied animal model for higher brain
      functions. Most of these comparative studies have been performed in the visual
      system. The early visual areas V1, V2 and V3, as well as the motion area MT are
      conserved in humans. Beyond these areas, differences between human and monkey
      functional organization are increasingly evident. At the regional level, the
      monkey inferotemporal and intraparietal complexes appear to be conserved in
      humans, but there are profound functional differences in the intraparietal cortex
      suggesting that not all its constituent areas are homologous. In the long term,
      fMRI offers opportunities to compare the functional anatomy of a variety of
      cognitive functions in the two species.

PMID- 15242692
TI  - Genes and the parsing of cognitive processes.
AB  - Now that the human genome has been sequenced there exists the possibility of
      identifying specific genes that affect human cognition. In this article, recent
      studies that have found associations between common gene variants and specific
      cognitive processes are reviewed. Several principles for evaluating this new
      field are also discussed. The interpretation of results is far from simple
      because a single gene can affect multiple processes, multiple genes can impact on
      a single process, and multiple cognitive processes are intercorrelated. In
      general, functional neuroimaging has been a more sensitive assay of cognitive
      processing than behavioral measures used alone, although there are important
      caveats regarding its use. Replicated findings so far involve associations
      between a COMT polymorphism and prefrontally-based executive functions and
      neurophysiology, and a BDNF polymorphism and medial-temporal-cortex based
      declarative memory processes. Implicit in this review is a concern that many of
      the cognitive paradigms used evolved for purposes well outside those described
      here. As such it may be necessary to view cognition in novel ways, based on
      constraints imposed by genomics and neurobiology, in order to increase the effect
      size of genotypic influences on cognition.

PMID- 15242693
TI  - EDR is a stress-related survival factor from stroma and other tissues acting on
      early haematopoietic progenitors (E-Mix).
AB  - The erythroid differentiation regulator (EDR) is a highly conserved autocrine
      factor produced in many tissues. Its haemoglobin synthesis-inducing activity for
      human and murine erythroleukaemia cell lines had been detected in WEHI-3
      conditioned medium. EDR functions were analysed in detail. It is released from
      cells immediately in response to various stressful conditions and enhances cell
      survival particularly at a lower concentration range and low cell density. At
      high cell density and high EDR concentration the opposite effect of an increase
      in cell death was observed. Its essential function within a tissue is considered
      to be the maintenance of growth homeostasis. Cells kept in culture for weeks show
      a decreasing responsiveness to EDR supply. This was also noted in freshly cloned
      EDR-responsive mouse erythroleukaemia cells pointing to a molecular adaptation
      process. Human haematopoietic progenitors were amplified 7-fold by EDR when kept
      at low cytokine levels. At saturating levels progenitors giving rise to at least
      two lineages in semisolid medium (E-mix) respond to EDR with an average 1.87-fold
      increase in colony numbers and a bell-shaped dose-response curve. Of the more
      mature BFU-E compartment a response was observed particularly in cases with low
      colony numbers. Given the release from irradiated stromal cells and the ability
      to partly substitute for stromal cells in the Burkitt's lymphoma cell line BL-70,
      EDR functions as a stromal survival factor for stroma-responsive cells.

PMID- 15242694
TI  - Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate
      with clinical outcome in metastatic breast cancer patients treated with
      chemotherapy.
AB  - INTRODUCTION: To assess the relationship of various growth factors and cytokines
      with the clinical outcome in metastatic breast cancer patients receiving
      chemotherapy. METHODS: Consecutive, metastatic breast cancer patients with
      measurable disease and receiving palliative chemotherapy were prospectively
      evaluated for the predictors of progression free survival (PFS) and overall
      survival (OAS) in relation to serum insulin, insulin resistance, interleukin-6
      (IL-6), and tumour necrosis factor-alpha (TNF-alpha). RESULTS: Estrogen receptor
      (ER) status, serum IL-6 and serum TNF- were the independent determinants of PFS,
      with RR=0.28 (0.13-0.60), P=0.001, RR=2.48 (1.24-5.61), P=0.012, and RR=0.48
      (0.23-1.01), P=0.053, respectively. The factors related with OAS in the
      multivariate analysis were histological grade (RR=7.88 (2.33-26.62), P=0.001), ER
      status (RR=0.18 (0.06-0.57), P=0.003), serum insulin (RR=0.87 (0.77-0.97),
      P=0.016), and serum IL-6 (RR=5.99 (1.89-18.97), P=0.002). CONCLUSIONS: We show
      for the first time that fasting serum insulin and TNF-alpha levels are
      independent predictors for OAS and PFS, respectively, in metastatic breast cancer
      patients. In addition, we also confirm that IL-6 is a poor prognosticator in this
      group. These results suggest that insulin and TNF-alpha are important
      biomolecules that may be directly involved in vivo in the progression of
      metastatic breast cancer.

PMID- 15242695
TI  - Burn injury induces an inhibitory signal in the lung Smad pathway.
AB  - Smad signaling mediates the cellular response to transforming growth factor-beta
      (TGF-beta). We hypothesize that variations in Smad signaling modify the response
      to TGF-beta signaling in the lung after injury. C57BLKS/J mice were subjected to
      an 18% surface area burn injury, sacrificed at specific time points and their
      lung tissue was harvested. Lung TGF-beta1 expression, as determined by RT-PCR,
      ELISA and PAI/Luciferase assay, was not affected by injury. Western blots for
      Smad2/3 and Smad4 on nuclear fractions revealed decreased Smad2, Smad3, and Smad4
      protein levels at 3h, while their total cellular levels did not differ from
      control mice. Smad7 protein increased transiently at 3 h. Correlating with Smad
      inhibition, transcription in type I alpha-2 collagen was also transiently
      depressed. By RT-PCR, Smad3 and Smad7 mRNAs decreased at 3 h, while Smad2 and
      Smad4 mRNA levels remained constitutive. Burn injury did not alter lung TGF-beta1
      expression but caused Smad inhibition through decreased nuclear translocation of
      Smad2, Smad3, and Smad4, and upregulated Smad7. Transcription was not the key
      regulatory step in Smad protein expression, as transient decreases in Smad3 and
      Smad7 mRNA did not correlate with protein levels. It appears that Smad activity
      may in part attenuate TGF-beta activity after burn injury.

PMID- 15242696
TI  - Low stimulated IL-4 secretion in PBMC from patients with chronic idiopathic
      urticaria.
AB  - An imbalance between the Th1 and Th2 arms of the cellular immune system has been
      reported in several autoimmune diseases but not in chronic idiopathic urticaria
      (CIU). Peak, total secretion and secretory pattern of the Th1 cytokines (IFNgamma
      and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and
      stimulated peripheral blood mononuclear cells (PBMC) from nineteen CIU patients,
      six acute urticaria patients and twelve controls. Stimulated IL-4 secretion was
      significantly reduced in CIU patients as indicated by their five- and three-fold
      lower peak levels and total IL-4 secretion, respectively. The IL-4 secretory
      pattern overtime was also markedly different in patients and controls. The late
      secretion of IFNgamma at 144 h was also reduced in CIU patients. These
      aberrations were not detectable in AU patients. Secretion of IL-2 was lower in
      CIU and AU patients as compared to controls while IL-10 secretion was comparable
      in the three groups. Our data demonstrate for the first time a predominantly
      reduced IL-4 secretion in CIU patients. This is associated with reduced secretion
      of both IL-2 and IFNgamma. These findings indicate a generalized down-regulation
      of both Th1 and Th2 cytokines' secretion in CIU.

PMID- 15242697
TI  - Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and
      subclinical renal injury at cardiac surgery.
AB  - Whilst elevated urinary transforming growth factor beta-1 (TGFbeta) is associated
      with chronic renal dysfunction its role in acute peri-operative renal dysfunction
      is unknown. In contrast, peri-operative increases in urinary IL-1 receptor
      antagonist (IL-1ra) and TNF soluble receptor-2 (TNFsr-2) mirror pro-inflammatory
      activity in the nephron and correlate with renal complications. Steroids modulate
      some plasma cytokines (decreasing TNFalpha, IL-8, IL-6 and increasing IL-10),
      whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri
      operative renal injury is unknown. Patients undergoing coronary artery bypass
      grafting with cardiopulmonary bypass (CPB) were randomised to receive
      methylprednisolone (n = 18) or placebo (n = 17) before induction of anaesthesia.
      Plasma and urinary pro- and anti-inflammatory cytokine balance was determined
      along with subclinical proximal tubular injury and dysfunction, measured by
      urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1
      microglobulin/creatinine ratios, respectively. In the control group compared with
      baseline, plasma IL-8, TNFalpha, IL-10, IL-1ra and TNFsr-2 were significantly
      elevated along with urinary IL-1ra, TNFsr-2 and TGFbeta1. Urinary NAG/creatinine
      and alpha-1-microglobulin/creatinine ratios rose from completion of
      revascularisation until 6 h with recovery at 24 h with a further rise in
      NAG/creatinine ratio at 48 h. Compared to placebo, the methylprednisolone group
      showed significantly reduced plasma IL-8, TNFalpha, IL-1ra and TNFsr-2 whereas
      plasma IL-10 increased. Compared to placebo, the methylprednisolone group
      demonstrated significantly reduced urinary NAG/creatinine ratio, TNFsr-2 and
      TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios
      increased. CONCLUSIONS: Methylprednisolone administration during cardiac surgery
      significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFbeta1 and
      subclinical renal injury but not dysfunction.

PMID- 15242698
TI  - Adiponectin and the systemic inflammatory response in weight-losing patients with
      non-small cell lung cancer.
AB  - The aim of the present study was to examine the relationship between adiponectin
      and the systemic inflammatory response in weight-losing patients with non-small
      cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins,
      interleukin-6, leptin (total and free) and adiponectin were carried out on
      healthy subjects (n = 13) and non-small cell lung cancer patients with weight
      loss (n = 20). The groups were age and sex matched. Compared with the controls
      the cancer group had a lower BMI (p < 0.01), mid-upper arm circumference (p <
      0.001), triceps skinfold thickness (p < 0.05) and circulating concentrations of
      albumin (p < 0.001), haemoglobin (p < 0.05), free and total leptin (p < 0.05) and
      adiponectin (p < 0.01). In contrast, the cancer group had elevated circulating
      concentrations of interleukin-6 and C-reactive protein concentrations (p <
      0.001). In the cancer group circulating adiponectin concentrations were
      significantly inversely correlated with both free (rs = -0.675, p = 0.001) and
      total leptin concentrations (rs = -0.690, p = 0.001). However, neither weight
      loss, interleukin-6 or C-reactive protein concentrations were correlated with
      either adiponectin, free or total leptin concentrations in the cancer group.
      These results suggest that adipokine production is normal and is unlikely to play
      a major role in the abnormal fat metabolism in weight-losing cancer patients.

PMID- 15242700
TI  - Advances in the study of Anopheles funestus, a major vector of malaria in Africa.
AB  - The recent literature on cytogenetic and molecular studies of Anopheles funestus,
      a major vector of malaria in Africa, is reviewed. Molecular data from West and
      Central Africa suggest a new species in the group closely allied to Anopheles
      rivulorum. Cytogenetic and molecular studies of populations from West, Central,
      East and southern Africa indicate considerable genetic structuring within An.
      funestus itself, which may well restrict the spread of pyrethroid resistance that
      has been demonstrated in southern Africa.

PMID- 15242701
TI  - Using RNA interference to develop dengue virus resistance in genetically modified
      Aedes aegypti.
AB  - Diseases caused by arthropod-borne viruses are significant public health
      problems, and novel methods are needed to control pathogen transmission. We
      hypothesize that genetic manipulation of Aedes aegypti mosquitoes can profoundly
      and permanently reduce vector competence and subsequent transmission of dengue
      viruses (DENV) to human hosts. We have identified RNA interference (RNAi) as a
      potential anti-viral, intracellular pathway in the vector that can be triggered
      by expression of virus-specific, double stranded RNAs (dsRNAs) to reduce vector
      competence to DENV. We identified DENV-derived RNA segments using recombinant
      Sindbis viruses to trigger RNAi, that when expressed in mosquitoes ablate
      homologous DENV replication and transmission. We also demonstrated that heritable
      expression of DENV-derived dsRNA in cultured mosquito cells can silence virus
      replication. We now have developed a number of transgenic mosquito lines that
      transcribe the effector dsRNA from constitutive promoters such as immediate early
      1 (baculovirus) and polyubiquitin (Drosophila melanogaster). We have detected
      DENV-specific small interfering RNAs, the hallmark of RNAi, in at least one of
      these lines. Surprisingly, none of these lines expressed dsRNA in relevant
      tissues (e.g., midguts) that will ultimately affect transmission. A major
      challenge now is to express the effector dsRNA from tissue-specific promoters to
      allow RNAi to silence virus replication at critical sites in the vector such as
      midguts and salivary glands. If successful, this strategy has the advantage of
      harnessing a naturally occurring vector response to block DENV infection in a
      mosquito vector and profoundly affect virus transmission.

PMID- 15242702
TI  - Insect-malaria parasites interactions: the salivary gland.
AB  - Mosquito salivary glands are organs specialized in the production of a complex
      mix of molecules that digest carbohydrates from plant nectars, and facilitate
      blood feeding by the lubrication of mouthparts and the inhibition of homeostasis.
      Malaria sporozoites invade salivary glands and are injected with the saliva into
      vertebrate hosts during blood feeding. Sporozoites utilize molecules on their
      surface coat and outer pellicle membrane to adhere and invade specific regions of
      the salivary gland lobes. They transverse the secretory cells and are stored in
      the salivary duct, where transcription of new genes prepares them for vertebrate
      host invasion. Although it is probably that specific carbohydrate molecules on
      the surface of salivary glands function as parasites receptors, these have not
      been identified, neither other molecules nor mechanisms used by the parasite to
      invade, survive and mature within these organs. The recent advances in the
      sequence of the genomes of Anopheles gambiae and Plasmodium falciparum, and new
      developments in genomics and proteomics may help to elucidate the participating
      molecules, their regulation and interactions.

PMID- 15242703
TI  - Mosquito--malaria interactions: a reappraisal of the concepts of susceptibility
      and refractoriness.
AB  - This paper considers the available literature on the transmission of malaria by
      insects and concludes that, in contrast to the commonly held view (that implies
      mosquitoes are naturally vectors of malaria), it is more useful to consider that
      mosquitoes, like plants, normally express a variety of gene products, which
      together render the host resistant to infection. The consequences of this
      hypothesis upon current research are that when studying the passage of the
      malarial parasite through a competent vector it is relevant to ask either 'How
      have the natural innate defences of the insect failed?' or 'What mechanisms has
      the parasite used to overcome these defences?' At the population level, the
      hypothesis is consistent with the conclusions of Koella et al. that the
      evolutionary cost of maintaining defence mechanisms that can render the mosquito
      refractory (e.g. melanization) has prevented fixation of the necessary gene(s) in
      the insect population. We simply extend that concept by stating the innate and
      genetic defences that confer the natural (and sometimes incomplete) resistance to
      infection are of sustainable cost, with the consequence that the encoding genes
      may become highly prevalent or fixed in a population.

PMID- 15242704
TI  - Mosquito transposable elements.
AB  - The completion of the genome assembly for the African malaria mosquito, Anopheles
      gambiae, and continuing genomic efforts for the yellow fever mosquito, Aedes
      aegypti, have allowed the use of bioinformatics tools to identify and
      characterize a diverse array of transposable elements (TEs) in these and other
      mosquito genomes. An overview of the types and number of both RNA-mediated and
      DNA-mediated TEs that are found in mosquito genomes is presented. A number of
      novel and interesting TEs from these species are discussed in more detail. These
      findings have significant implications for our understanding of mosquito genome
      evolution and for future modifications of natural mosquito populations through
      the use of TE-mediated genetic transformation.

PMID- 15242706
TI  - The molecular basis of insecticide resistance in mosquitoes.
AB  - Insecticide resistance is an inherited characteristic involving changes in one or
      more insect gene. The molecular basis of these changes are only now being fully
      determined, aided by the availability of the Drosophila melanogaster and
      Anopheles gambiae genome sequences. This paper reviews what is currently known
      about insecticide resistance conferred by metabolic or target site changes in
      mosquitoes.

PMID- 15242707
TI  - Mosquito midgut barriers to malaria parasite development.
AB  - Malaria is one of the deadliest infectious diseases and kills more than one
      million people every year. For transmission to occur, the malaria parasite has to
      complete an elaborate developmental program in hostile mosquito environment.
      Thus, understanding the molecular mechanisms by which mosquitoes limit the
      parasite development may lead to new methods for controlling malaria. There has
      been considerable progress during the last decade in this research area. This
      review focuses on the mosquito response to midgut invasion of the malaria
      parasite and examines the role of mosquito digestive enzymes, peritrophic matrix
      and microvillar proteins as barriers to parasite development.

PMID- 15242708
TI  - Immune responses in Anopheles gambiae.
AB  - Transmission of human malaria requires a successful development of Plasmodium
      parasites in anopheline mosquitoes. Insects have developed efficient immune
      responses to oppose microbial and eukaryotic invaders. The completion of the
      sequencing of the Anopheles genome provides a wealth of information on putative
      immune genes that are homologous to components of the Drosophila and mammalian
      immune systems. In this review, we will summarize our present knowledge of immune
      responses in the mosquito Anopheles gambiae and attempt a comparative analysis of
      insect immune systems.

PMID- 15242705
TI  - Olfactory regulation of mosquito-host interactions.
AB  - Mosquitoes that act as disease vectors rely upon olfactory cues to direct several
      important behaviors that are fundamentally involved in establishing their overall
      vectorial capacity. Of these, the propensity to select humans for blood feeding
      is arguably the most important of these olfactory driven behaviors in so far as
      it significantly contributes to the ability of these mosquitoes to transmit
      pathogens that cause diseases such as dengue, yellow fever and most significantly
      human malaria. Here, we review significant advances in behavioral, physiological
      and molecular investigations into mosquito host preference, with a particular
      emphasis on studies that have emerged in the post-genomic era that seek to
      combine these approaches.

PMID- 15242709
TI  - Interactions between malaria parasites and their mosquito hosts in the midgut.
AB  - This review examines what is presently known of the molecular interactions
      between Plasmodium and Anopheles that take place in the latter's midgut upon
      ingestion of the parasites with an infectious blood meal. In order to become
      'established' in the gut and to transform into a sporozoite-producing oocyst, the
      malaria parasite needs to undergo different developmental steps that are often
      characterized by the use of selected resources provided by the mosquito vector.
      Moreover, some of these resources may be used by the parasite in order to
      overcome the insect host's defence mechanisms. The molecular partners of this
      interplay are now in the process of being defined and analyzed for both
      Plasmodium and mosquito and, thus, understood; these will be presented here in
      some detail.

PMID- 15242710
TI  - Nutritional regulation of JH synthesis: a mechanism to control reproductive
      maturation in mosquitoes?
AB  - Juvenile hormone (JH) titers must be modulated to permit the normal progress of
      development and reproduction in mosquitoes. In adult female Aedes aegypti, JH
      levels are low at adult eclosion, elevated in sugar-fed females and low again
      after a blood meal. Although degradation plays a role, JH titer is fundamentally
      determined by the rate of biosynthesis in the corpora allata gland (CA). CA from
      newly eclosed females (0-1 h after emergence) exhibit a very low basal JH
      biosynthetic activity, Aedes-allatotropin stimulates the CA in newly emerged
      females to produce JH. There is a correlation between nutritional reserves at
      adult emergence (teneral reserves) and CA activity. JH synthesis is significantly
      reduced in teneral females that emerge with low nutritional reserves. Taking a
      blood meal results in a reduction of CA activity. The biosynthetic activity of
      Ae. aegypti CA is significantly inhibited by factors present in the head, as well
      as by Anopheles gambiae PISCF-allatostatin. Nutritional signals affect the
      release of allatotropin and allatostatins by the brain resulting in the
      activation or inhibition of JH synthesis. JH is therefore an important part of a
      transduction mechanism that connects changes in the nutritional status with
      activation of specific physiological events during reproduction.

PMID- 15242711
TI  - Tn5 as an insect gene vector.
AB  - The purpose of this study was to explore alternatives to insect-derived
      transposable elements as insect gene vectors with the intention of improving
      existing insect transgenesis methods. The mobility properties of the bacterial
      transposon, Tn5, were tested in mosquitoes using a transient transposable element
      mobility assay and by attempting to create transgenic insects. Tn5 synaptic
      complexes were assembled in vitro in the absence of Mg(2+) and co-injected with a
      target plasmid into developing yellow fever mosquito, Aedes aegypti, embryos.
      Target plasmids recovered from embryos a day later were screened for the presence
      of Tn5. Recombinants (transposition events) were found at a frequency of 1.2 x
      10(-3). Some transposition events did not appear to be associated with canonical
      9 bp direct duplications at the site of insertion and also were associated with
      either deletions or rearrangements. A Tn5 element containing the brain-specific
      transgene, 3 x P3DsRed, was assembled into synaptic complexes in vitro and
      injected into pre-blastoderm embryos of Ae. aegypti. Of the approximately 900
      embryos surviving injection and developing into adults, two produced transgenic
      progeny. Both transgenic events involved the co-integrations of approximately
      five elements resulting in nested and tandem arrayed Tn5::3 x P3DsRed elements.
      This study extends the known host range of Tn5 to insects and makes available to
      insect biologists and others another eukaryotic genome-manipulation tool. The
      hyperactivity of synaptic complexes may be responsible for the unusual clustering
      of elements and managing this aspect of the element's behavior will be important
      in future applications of this technology to insects.

PMID- 15242712
TI  - Impact of population age structure on Wolbachia transgene driver efficacy:
      ecologically complex factors and release of genetically modified mosquitoes.
AB  - Wolbachia symbionts hold theoretical promise as a way to drive transgenes into
      insect vector populations for disease prevention. For simplicity, current models
      of Wolbachia dynamics and spread ignore ecologically complex factors such as the
      age structure of vector populations and overlapping vector generations. We
      developed a model including these factors to assess their impact on the process
      of Wolbachia spread into populations of three mosquito species (Anopheles
      gambiae, Aedes aegypti and Culex pipiens). Depending on the mosquito species,
      Wolbachia parameters, released mosquito life stage and initial age structure of
      the target population, the number of Wolbachia-infected mosquitoes that we
      predict would need to be released ranged from less than the threshold calculated
      by the simple model to a 10-30-fold increase. Transgenic releases into age
      structured populations, which is an expectation for wild mosquitoes, will be
      difficult and depending on the circumstances may not be economically or
      logistically feasible due to the large number of infected mosquitoes that must be
      released. Our results support the perspective that understanding ecological
      factors is critical for designing transgenic vector-borne disease control
      strategies.

PMID- 15242713
TI  - Aedes aegypti genomics.
AB  - The mosquito, Aedes aegypti, is the primary, worldwide arthropod vector for the
      yellow fever and dengue viruses. As it is also one of the most tractable mosquito
      species for laboratory studies, it has been and remains one of the most
      intensively studied arthropod species. This has resulted in the development of
      detailed genetic and physical maps for Ae. aegypti and considerable insight into
      its genome organization. The research community is well-advanced in developing
      important molecular tools that will facilitate a whole genome sequencing effort.
      This includes generation of BAC clone end sequences, physical mapping of selected
      BAC clones and generation of EST sequences. Whole genome sequence information for
      Ae. aegypti will provide important insight into mosquito chromosome evolution and
      allow for the identification of genes and gene function. These functions may be
      common to all mosquitoes or perhaps unique to individual species, possibly
      specific to host-seeking and blood-feeding behaviors, as well as the innate
      immune response to pathogens encountered during blood-feeding. This information
      will be invaluable to the global effort to develop novel strategies for
      preventing arthropod-borne disease transmission.

PMID- 15242715
TI  - Classification and epidemiology of hypersensitivity drug reactions.
AB  - Nonimmune hypersensitivity reactions are unpredictable adverse drug reactions
      that are clinically similar to allergic reactions for which no drug-specific
      antibodies or T lymphocytes are identified. Few tools allow a definite diagnosis,
      and most of the available ones need to be validated. True epidemiologic data are
      limited, and most of the available information on the incidence, mortality, and
      socioeconomic impact should be discussed with caution.

PMID- 15242714
TI  - Wolbachia and cytoplasmic incompatibility in mosquitoes.
AB  - Wolbachia are maternally inherited bacteria that induce cytoplasmic
      incompatibility in mosquitoes, and are able to use these patterns of sterility to
      spread themselves through populations. For this reason they have been proposed as
      a gene drive system for mosquito genetic replacement, as well as for the
      reduction of population size or for modulating population age structure in order
      to reduce disease transmission. Here, recent progress in the study of mosquito
      Wolbachia is reviewed. We now have much more comprehensive estimates of the
      parameters that can affect the spread of Wolbachia through natural populations
      from low starting frequencies, and for waves of spread to be maintained in the
      face of partial barriers to gene flow. In Aedes albopictus these dynamics are
      extremely favourable, with very high maternal transmission fidelity and levels of
      incompatibility recorded. Correspondence between measurements taken in the lab
      and field is much better than in the Drosophila simulans model system. Important
      research goals are also discussed, including Wolbachia transformation,
      interspecific transfer and the elucidation of the mechanisms of incompatibility
      and rescue; all will be aided by a wealth of new Wolbachia genome information.

PMID- 15242716
TI  - Clinical evaluation and management of drug hypersensitivity.
AB  - Adverse drug reactions are a major health problem in the inpatient and outpatient
      clinical setting. Although all of the immune mechanisms of drug reactions are not
      well characterized, a detailed medication history, knowledge of the signs and
      symptoms associated with known immune mechanisms, and knowledge of the types of
      medications typically associated with distinct immune reactions are helpful in
      implicating the causative drug. Standardized testing for drug reactions is
      limited, especially for non-IgE-mediated reactions. Management consists of
      stopping the offending drug, treating the acute reaction, and making a
      determination concerning future use of the drug.

PMID- 15242717
TI  - Immune mechanism of drug hypersensitivity.
AB  - Drug hypersensitivity reactions can lead to a great variety of different
      diseases. The main cause is a specific interaction of antibodies or T cells with
      a drug. In addition to the hapten concept, some drugs can bind directly to T-cell
      receptors and stimulate them. Based on recent investigation on different
      exanthemas, an extended classification of the Gell and Coombs type IV reaction is
      proposed.

PMID- 15242718
TI  - Dermatologic drug reactions.
AB  - Cutaneous drug reactions have a variety of clinical presentations. This review
      focuses on the most common or severe cutaneous reaction patterns. Knowledge of
      the clinical morphology and the most commonly associated medication aids in rapid
      diagnosis and institution of the appropriate therapy.

PMID- 15242719
TI  - Drug desensitization.
AB  - Although most patients who report a history of drug allergy are not truly
      allergic, this article focuses on those individuals with confirmed drug
      hypersensitivity. Desensitization is an immunologic method that allows allergic
      patients to receive the sensitizing drug safely. Classically, the procedure is
      applied in IgE-mediated reactions, but its use has been extended to other drug
      reactions. The most common clinical scenarios wherein desensitization may be
      needed are reviewed. The discussion includes rapid desensitization of patients
      with IgE-mediated allergies to penicillin and other classes of antibiotics, and
      sulfonamide desensitization of HIV-positive patients.

PMID- 15242720
TI  - Dilemmas and controversies in penicillin allergy.
AB  - Since the initial reports of penicillin and beta-lactam drugs causing allergic
      reactions, much has been elucidated regarding their pathophysiology and mechanism
      of action. Despite advances in testing for penicillin allergy, with IgE
      antibodies and skin tests available for the major and minor determinants of
      penicillin, these reactions remain a challenge to all physicians. They have
      characteristically been classified according to mechanism and time. Herein, the
      authors propose a classification system of penicillin allergy based on
      immunologic mechanisms.

PMID- 15242721
TI  - Cephalosporin allergy.
AB  - Allergic reactions to cephalosporins may occur because of sensitization to
      cephalosporin determinants shared with penicillin or to unique cephalosporin
      haptens. The exact nature of the haptenic determinants resulting from the
      degradation of currently available cephalosporins is incompletely understood.
      Cephalosporin skin testing or specific IgE immunoassays have limited clinical
      utility. Patients with a history of allergy to cephalosporins or penicillin may
      be at increased risk for a reaction to cephalosporins. Skin testing for an
      allergy to penicillin may be helpful in patients with a history of penicillin
      allergy who have a clinical indication for cephalosporin use. Most of these
      patients have negative tests and should not be at increased risk for a reaction
      to cephalosporins.

PMID- 15242722
TI  - Sulfonamide hypersensitivity.
AB  - Sulfonamide antibiotics can result in a wide variety of hypersensitivity
      reactions. No validated diagnostic tests are available for sulfonamide reactions;
      therefore, clinicians must rely on the combination of a careful patient history,
      review of medical records, and a sound knowledge base regarding the common
      clinical manifestations of sulfonamide hypersensitivity reactions. Although HIV
      infected individuals have a high risk for hypersensitivity reactions to
      sulfamethoxazole, readministering the drug can usually be performed safely by
      using a desensitization protocol. Sulfonamide-containing medications that are not
      antibiotics also have the capacity for causing hypersensitivity reactions.
      Whether the sulfa moiety confers a risk of cross-reaction is controversial. The
      preponderance of available evidence suggests that sulfonamide antibiotics
      probably do not cross-react with sulfonamide nonantibiotics.

PMID- 15242724
TI  - Anaphylactoid and adverse reactions to radiocontrast agents.
AB  - Over the past 75 years, radiocontrast agents have provided numerous diagnostic
      and therapeutic advances. The benefits of these agents must be weighed against
      the potential risks for each individual undergoing radiologic tests. This summary
      is intended to be a guide for the allergy and immunology specialist to direct him
      or her to the current literature regarding adverse reactions to traditional and
      less commonly used radiologic contrast agents.

PMID- 15242723
TI  - Aspirin and NSAID sensitivity.
AB  - Aspirin and the older nonsteroidal anti-inflammatory drugs (NSAIDs) that block
      cyclo-oxygenase-1 (COX-1) induce asthma attacks in patients with aspirin
      exacerbated respiratory disease and urticaria in patients with chronic idiopathic
      urticaria. Weak inhibitors of COX-1, such as acetaminophen and salsalate,
      crossreact also but only with high doses of the drugs. Partial inhibitors of both
      COX-1 and COX-2, such as nimesulide and meloxicam, also cross-react but only at
      high drug doses. COX-2 inhibitors do not cross-react; however, all NSAIDs,
      including the selective COX-2 inhibitors, can sensitize patients and induce
      urticaria or anaphylaxis on next exposure to the drug.

PMID- 15242725
TI  - HIV and drug allergy.
AB  - Twenty individual antiretroviral drugs and two coformulation products are
      approved by the US Food and Drug Administration for the treatment of HIV-infected
      individuals. Many of these drugs have been associated with
      allergic/hypersensitivity reactions to varying degrees. The antiretroviral drugs
      that are most commonly associated with these types of reactions are abacavir, all
      of the nonnucleoside reverse transcriptase inhibitors, and amprenavir.
      Trimethoprim-sulfamethoxazole, although not an antiretroviral drug, is
      extensively used for the treatment and prophylaxis of HIV-related opportunistic
      infections and has been associated with a significant rate of adverse reactions.
      The authors provide an overview of these drug-related reactions and discuss their
      pathogenesis and management.

PMID- 15242726
TI  - Multiple antibiotic allergy syndrome.
AB  - Allergists/immunologists are commonly referred patients with histories of
      multiple antibiotic allergies and must determine what antibiotics they can safely
      use. This review covers articles published through September 2003. The history
      and definition of multiple antibiotic allergy syndrome are discussed. The
      clinical and laboratory evidence suggesting that certain individuals make
      allergic antibody to unrelated antibiotics is explored. A framework for dealing
      with this potentially vexing problem on a clinical level is developed. Areas that
      require additional research and development are outlined.

PMID- 15242728
TI  - Mending the broken heart: ischemic preconditioning-stimulated myocardial
      angiogenesis.

PMID- 15242729
TI  - Glutamate transport in the heart: lessons learned from the brain.

PMID- 15242730
TI  - Glycogen in the heart--an expanded view.

PMID- 15242731
TI  - Genetic manipulation of myocardial beta-adrenergic receptor activation and
      desensitization.
AB  - Heart failure (HF) represents one of the leading causes of morbidity and
      mortality in developed nations today. Although this disease process represents a
      final common endpoint for several entities, including hypertension, coronary
      artery disease, and cardiomyopathy, a predominant characteristic of end-stage HF
      is an altered beta-adrenergic receptor signaling cascade. In the heart, beta
      adrenergic receptors (beta ARs), members of the superfamily of G-protein-coupled
      receptors (GPCRs), modulate cardiac function by controlling chronotropic,
      inotropic, and lusitropic responses to catecholamines of the sympathetic nervous
      system. In HF, beta ARs are desensitized and downregulated in a maladaptive
      response to chronic stimulation. This process is largely mediated by G-protein
      coupled receptor kinases (GRKs), which phosphorylate GPCRs leading to functional
      uncoupling. The most abundant cardiac GRK, known as GRK2 or beta AR kinase 1
      (beta ARK1), is increased in human HF, and has been implicated in the
      pathogenesis of dysfunctional cardiac beta AR signaling. The association of beta
      ARs and GRKs with impaired cardiac function has been extensively studied using
      transgenic mouse models, which have demonstrated that beta ARK1 plays a vital
      role in the regulation of myocardial beta AR signaling. These findings have
      caused beta ARs and GRKs to be regarded as potential therapeutic targets, and
      gene therapy strategies have been used to manipulate the beta AR signaling
      pathway in myocardium, leading to improved function in the compromised heart.
      Ultimately, these genetic modifications of the heart may represent new potential
      therapies for human HF.

PMID- 15242732
TI  - Coronary microembolization.
AB  - Atherosclerotic plaque rupture is a key event in the pathogenesis of acute
      coronary syndromes and during coronary interventions. Atherosclerotic plaque
      rupture does not always result in complete thrombotic occlusion of the entire
      epicardial coronary artery with subsequent acute myocardial infarction, but may
      in milder forms result in the embolization of atherosclerotic and thrombotic
      debris into the coronary microcirculation. This review summarizes the available
      morphological evidence for coronary microembolization in patients who died from
      coronary artery disease, most notably from sudden death. Then the experimental
      pathophysiology of coronary microembolization in animal models of acute coronary
      syndromes is detailed. Finally, the review presents the available clinical
      evidence for coronary microembolization in patients, highlights its key features-
      arrhythmias, contractile dysfunction, microinfarcts and reduced coronary reserve-
      , compares these features to those of the experimental model and addresses its
      prevention by mechanical protection devices and glycoprotein IIb/IIIa antagonism.

PMID- 15242734
TI  - Endogenous glycogen prevents Ca2+ overload and hypercontracture in harp seal
      myocardial cells during simulated ischemia.
AB  - The purpose of this study was to determine if elevated myocardial glycogen
      content could obviate Ca(2+) overload and subsequent myocardial injury in the
      setting of low oxygen and diminished exogenous substrate supplies. Isolated harp
      seal cardiomyocytes, recognized as having large glycogen stores, were incubated
      under conditions simulating ischemia (oxygen and substrate deprivation) for 1 h.
      Rat cardiomyocytes were used for comparison. Freshly isolated seal cardiomyocytes
      contained approximately 10 times more glycogen than those from rats (479 +/- 39
      vs. 48 +/- 5 nmol glucose/mg dry weight (dry wt), mean +/- S.E., n = 6), and
      during ischemia lactate production was significantly greater in seal compared to
      rat cardiomyocytes (660 +/- 99 vs. 97 +/- 14 nmol/mg dry wt), while glycogen
      content decreased both in seal (from 479 +/- 39 to 315 +/- 58 nmol glucose/mg dry
      wt) and rat cardiomyocytes (from 48 +/- 5 to 18 +/- 5 nmol glucose/mg dry wt).
      Cellular ATP was well maintained in ischemic seal cardiomyocytes, whereas it
      showed a 65% decline (from 31 +/- 3 to 11 +/- 1 nmol ATP/mg dry wt) in rat
      cardiomyocytes. Similarly, total seal cardiomyocyte Ca(2+) content was not
      affected by ischemia, while Ca(2+) increased from 8.5 +/- 2.0 to 13.3 +/- 2.0
      nmol/mg dry wt in ischemic rat myocytes. Rat cardiomyocytes also showed a notable
      decline in the percentage of rod-shaped cells in response to ischemia (from 66 +/
      4% to 30 +/- 3%), and cell morphology was unaffected in seal incubations.
      Addition of iodoacetate (IAA, an inhibitor of glycolysis) to seal cardiomyocytes,
      on top of substrate and oxygen deprivation, reduced the cellular content of ATP
      by 52.9 +/- 4.4% (from 25 +/- 4 to 11 +/- 2 nmol ATP/mg dry wt) and the
      percentage of rod-shaped myocytes from 51 +/- 3% to 28 +/- 4%, while total Ca(2+)
      content was unchanged by these conditions. Seal cardiomyocytes thus tolerate low
      oxygen conditions better than rat cardiomyocytes. This finding is most likely due
      to a higher glycolysis rate in seals, fueled by larger myocardial glycogen
      stores.

PMID- 15242733
TI  - Localization and function of the brain excitatory amino acid transporter type 1
      in cardiac mitochondria.
AB  - Glutamate is the only amino acid extracted by healthy myocardium in net amounts,
      with uptake further increased during hypoxic or ischemic conditions. Glutamate
      supplementation provides cardioprotection from hypoxic and reperfusion injury
      through several metabolic pathways that depend upon adequate transport of
      glutamate into the mitochondria. Glutamate transport across the inner
      mitochondrial membrane is a key component of the malate/aspartate shuttle.
      Glutamate transport in the brain has been well characterized since the discovery
      of the excitatory amino acid transporter (EAAT) family. We hypothesize that a
      protein similar to EAAT1 found in brain may function as a glutamate transporter
      in cardiac mitochondria. Rat heart total RNA was screened by reverse
      transcriptase-polymerase chain reaction with an array of primer pairs derived
      from the rat brain EAAT1 cDNA sequence, yielding a 3786-bp cDNA comprising a 1638
      bp open reading frame identical to rat brain EAAT1 with flanking 5'- and 3'
      untranslated regions. Northern blot analysis confirmed a 4-kb mRNA product in rat
      heart and brain, with greater abundance in brain. A protein of the predicted
      approximate 60-kD size was recognized in myocardial lysates by an anti-EAAT1
      polyclonal antibody produced against an amino-terminal peptide from human EAAT1.
      The protein enriched in rat heart mitochondria by immunoblot, co-localized with
      the mitochondrial protein cytochrome c by immunohistochemistry, and further
      localized to the inner mitochondrial membrane upon digitonin fractionation of the
      mitochondria. In myocytes overexpressing EAAT1, activity of the malate/aspartate
      shuttle increased by 33% compared to non-transfected cells (P = 0.004). These
      data indicate that EAAT1 is expressed in myocardial mitochondria, and functions
      in the malate/aspartate shuttle, suggesting a role for EAAT1 in myocardial
      glutamate metabolism.

PMID- 15242735
TI  - Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in
      naive myocardium but is essential for the development of late preconditioning.
AB  - The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion
      injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(
      /-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion
      injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of
      reperfusion. When wild-type mice were preconditioned with six cycles of 4-min
      coronary occlusion/4-min reperfusion 24 h before the 30-min occlusion, infarct
      size was reduced from 58.6 +/- 1.9% of the risk region to 19.3 +/- 3.6%,
      indicating a late preconditioning (PC) effect. In non-preconditioned TNF-alpha(-/
      ) mice, infarct size was similar to that observed in wild-type mice (55.5 +/-
      3.7%). However, in TNF-alpha(-/-) mice preconditioned with six
      occlusion/reperfusion cycles 24 h earlier, infarct size was not reduced (55.2 +/-
      5.7%), indicating that the late PC protection against infarction was completely
      abolished. While minimal TNF-alpha immunoreactivity was detected in sham-operated
      hearts, extensive TNF-alpha expression was noted in the cytoplasm of
      cardiomyocytes in the ischemic/reperfused region 30 min after the PC ischemia. At
      30 min after PC, wild-type mice exhibited increased DNA-binding activity of
      nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) and nuclear
      translocation of p65, c-Jun and c-Fos; all of these changes were absent in TNF
      alpha(-/-) mice. These data demonstrate that TNF-alpha does not modulate infarct
      size in the naive (non-preconditioned) state but is essential for the development
      of the late phase of ischemic PC, possibly via the activation of NF-kappa B and
      AP-1 transcription factors.

PMID- 15242736
TI  - Mitochondrial Ca2+ flux and respiratory enzyme activity decline are early events
      in cardiomyocyte response to H2O2.
AB  - Oxidative stress is involved in mitochondrial apoptosis, and plays a critical
      role in ischemic heart disease and cardiac failure. Exposure of cardiomyocytes to
      H(2)O(2) leads to oxidative stress and mitochondrial dysfunction. In this study,
      we investigated the temporal order of mitochondrial-related events in the
      neonatal rat cardiomyocyte response to H(2)O(2) treatment. At times ranging from
      10 to 90 min after H(2)O(2) treatment, levels were determined for respiratory
      complexes I, II, IV and V, and citrate synthase activities, mitochondrial Ca(2+)
      flux, intracellular oxidation, mitochondrial membrane potential and apoptotic
      progression. Complexes II and IV activity levels were significantly reduced
      within 20 min of H(2)O(2) exposure while complexes I and V, and citrate synthase
      were unaffected. Mitochondrial membrane potential declined after 20 and 60 min of
      H(2)O(2) exposure while intracellular oxidation, declining complex I activity and
      apoptotic progression were detectable only after 60 min. Measurement of
      mitochondrial Ca(2+) ([Ca(2+)](m)) using rhodamine 2 detected an early
      accumulation of [Ca(2+)](m) occurring between 5 and 10 min. Pretreatment of
      cardiomyocytes with either ruthenium red or cyclosporin A abrogated the H(2)O(2)
      induced decline in complexes II and IV activities, indicating that [Ca(2+)](m)
      flux and onset of mitochondrial permeability transition pore opening likely
      precede the observed early enzymatic decline. Our findings suggest that
      [Ca(2+)](m) flux represents an early pivotal event in H(2)O(2)-induced
      cardiomyocyte damage, preceding and presumably leading to reduced mitochondrial
      respiratory activity levels followed by accumulation of intracellular oxidation,
      mitochondrial membrane depolarization and apoptotic progression concomitant with
      declining complex I activity.

PMID- 15242737
TI  - Inhibition of COX pathway in experimental myocardial infarction.
AB  - Release of inflammatory mediators within the ischemic myocardium has long been
      thought to contribute to myocardial damage and dysfunction. Myocardial infarction
      (MI) and congestive heart failure (CHF) were induced in rats by ligating the left
      coronary artery. Animals were treated with the selective cyclooxygenase-2 (COX-2)
      inhibitor-5,5-dimethyl-3-(3-fluorophenyl1)-4-(4-methyl-sulphonyl-2(5H)-fluranone
      (DFU), low-, high-dose acetyl salicylic acid (aspirin), or vehicle for 3 months.
      Strong immunoreactivity for COX-2 was detected in the cardiomyocytes, vascular
      endothelial cells, and macrophages in the infarcted myocardium. Compared to the
      vehicle, treatment with DFU significantly reduced left ventricular end-diastolic
      pressure, central venous pressure, lung wet/dry ratio and infarct size, and
      improved cardiac contractility (P < 0.05). In comparison, treatment with low or
      high doses of aspirin did not significantly impact any of these parameters. These
      findings demonstrate that induction of myocardial COX-2 in rats with CHF
      secondary to MI contributes to the cardiac injury and dysfunction associated with
      this disease, and that therapy aimed at inhibiting this enzymatic pathway at the
      onset of the disease may be beneficial in the treatment of MI and CHF.

PMID- 15242738
TI  - Characterization of a KCNQ1/KVLQT1 polymorphism in Asian families with LQT2:
      implications for genetic testing.
AB  - Congenital long QT syndrome (LQTS) is a genetic disease that predisposes affected
      individuals to arrhythmias, syncope, and sudden death. Mutations in several ion
      channel genes have been discovered in different families with LQTS: KCNQ1
      (KVLQT1, LQT1), KCNH2 (HERG, LQT2), SCN5A (LQT3), KCNE1 (minK, LQT5), and KCNE2
      (MiRP1, LQT6). Previously, the P448R-KVLQT1 missense mutation has been reported
      as an LQT1-causing mutation. In this report, we demonstrate the presence of the
      P448R polymorphism in two, unrelated Chinese LQTS families. Although absent from
      500 reference alleles derived from 150 white and 100 African-American subjects,
      P448R was present in 14% of healthy Chinese volunteers. Given the inconsistencies
      between the genotype (LQT1) and clinical phenotype (LQT2) in our two LQTS
      families, together with the finding that the P448R appears to be a common, ethnic
      specific polymorphism, mutational analysis was extended to the other LQTS-causing
      genes resulting in the identification of distinct HERG missense mutations in each
      of these two families. Heterologous expression of P448R-KVLQT1 yielded normal,
      wild-type (WT) currents. In contrast, the two unique HERG mutations resulted in
      dominant-negative suppression of the WT HERG channel. Our study has profound
      implications for those engaged in genetic research. Importantly, one child of the
      original proband was initially diagnosed with LQT1 based upon the presence of
      P448R-KVLQT1 and was treated with beta-blockers. However, he did not possess the
      subsequently determined LQT2-causing mutation. On the other hand, his untreated
      P448R-negative brother harbored the true, disease-causing HERG mutation. These
      findings underscore the importance of distinguishing channel polymorphisms from
      mutations pathogenic for LQTS and emphasize the importance of using appropriate
      ethnically matched controls in the genotypic analysis of LQTS.

PMID- 15242740
TI  - The sarcoplasmic reticulum proteins are targets for calpain action in the
      ischemic-reperfused heart.
AB  - Ca(2+) overload and free-radical injury are two mutually non-exclusive phenomena
      suggested to cause myocardial ischemia-reperfusion (IR)-induced contractile
      dysfunction; however, the mechanisms underlying their effects are not clear. One
      possible mechanism is the proteolytic modification of proteins by Ca(2+)
      dependent proteases, such as calpains, which are activated during Ca(2+) overload
      that occurs in IR. The sarcoplasmic reticulum (SR) plays a central role in
      mediating cardiac contractility and therefore any impairment in SR function will
      induce cardiac contractile dysfunction. We therefore investigated the possibility
      whether SR proteins were the target for calpain action in IR. Langendorff
      perfused rat hearts were subjected to IR in the presence and absence of
      leupeptin, a calpain inhibitor and the effects of calpain inhibition was examined
      on cardiac performance, SR function, and its regulation by protein
      phosphorylation as well as expression of SR Ca(2+)-cycling and -regulatory
      proteins. Our results show a depression in cardiac contractile function and
      activation of calpain during IR. Treatment with leupeptin recovered cardiac
      contractile function and attenuated calpain activity in IR hearts. The
      cardioprotection observed upon leupeptin treatment was associated with improved
      SR function and regulation. The recovery in SR function and regulation was
      consistent with prevention of IR-induced decrease in the expression of key SR
      Ca(2+)-handling and -regulatory proteins. Our results suggest that a
      downregulation of SR proteins by calpain may be a mechanism by which Ca(2+)
      overload causes cardiac contractile dysfunction during IR.

PMID- 15242739
TI  - Post-transcriptional alterations in the expression of cardiac Na+ channel
      subunits in chronic heart failure.
AB  - Clinical and experimental evidence has recently accumulated about the importance
      of alterations of Na(+) channel (NaCh) function and slow myocardial conduction
      for arrhythmias in infarcted and failing hearts (i.e., heart failure, HF). The
      present study evaluated the molecular mechanisms of local alterations in the
      expression of NaCh subunits which underlie Na(+) current (I(Na)) density decrease
      in HF. HF was induced in five dogs by sequential coronary microembolization and
      developed approximately 3 months after the last embolization (left ventricle
      (LV), ejection fraction = 27 +/- 7%). Five normal dogs served as a control group.
      Ventricular cardiomyocytes were isolated enzymatically from LV mid-myocardium and
      I(Na) was measured by whole-cell patch-clamp. The mRNA encoding the cardiac
      specific NaCh alpha-subunit Na(v)1.5, and one of its auxiliary subunits beta 1
      (NaCh beta 1), were analyzed by competitive reverse transcription-polymerase
      chain reaction. Protein levels of Na(v)1.5, NaCh beta 1 and NaCh beta 2 were
      evaluated by western blotting. The maximum density of I(Na)/C(m) was decreased in
      HF (n = 5) compared to control hearts (33.2 +/- 4.4 vs. 50.0 +/- 4.9 pA/pF, mean
      +/- S.E.M., n = 5, P < 0.05). The steady-state inactivation and activation of
      I(Na) remained unchanged in HF compared to control hearts. The levels of mRNA
      encoding Na(v)1.5, and NaCh beta 1 were unaltered in FH. However, Na(v)1.5
      protein expression was reduced about 30% in HF, while NaCh beta 1 and NaCh beta 2
      protein were unchanged. We conclude that experimental HF in dogs results in post
      transcriptional changes in cardiac NaCh alpha-subunit expression.

PMID- 15242741
TI  - Cellular and molecular mechanisms of systolic and diastolic dysfunction in an
      avian model of dilated cardiomyopathy.
AB  - We investigated the cellular and molecular mechanisms of systolic and diastolic
      dysfunction in a furazolidone (Fz)-induced model of dilated cardiomyopathy (DCM)
      in turkey poults. Serial echocardiograms disclosed marked systolic dysfunction in
      the Fz-treated poults, and ventricular weight and left ventricular (LV)/body
      weight ratio were significantly increased. Isolated heart experiments were
      performed to determine LV pressure-volume (P-V) relationships. In addition, LV
      sarcomere lengths (SLs) were measured after hearts had been fixed, and wall
      stress (sigma)-SL relationships were determined. When compared to control hearts,
      LV chamber volume in DCM hearts was approximately 3-fold increased, the active or
      developed LV P-V relationship was markedly depressed, the passive or diastolic P
      V relationship was steeper, and SLs were significantly shorter. However, the
      developed sigma-SL relationships of DCM and control hearts were not different
      indicating that intrinsic myocardial capacity to generate active force is
      unaffected in this model of DCM. In contrast, passive sigma, and passive tension
      in trabecular muscle preparations increased much more steeply with SL in DCM than
      normal hearts. Trabecular muscle experiments disclosed that the increase in
      passive myocardial stiffness was primarily collagen based. Titin, the giant
      sarcomeric molecule, which is an important determinant of passive myocyte
      properties in normal myocardium, did not contribute significantly to increased
      passive myocardial stiffness in DCM. We conclude that increased collagen-based
      passive myocardial stiffness is the major cause of the steeper passive or
      diastolic P-V relationship in DCM. Further, altered passive myocardial properties
      and ventricular geometry in DCM play a critical role to reduce ventricular
      systolic function by limiting SL extension during diastole, thereby limiting the
      use of the myocardial length-tension relationship.

PMID- 15242742
TI  - Oscillatory shear stress upregulation of endothelial nitric oxide synthase
      requires intracellular hydrogen peroxide and CaMKII.
AB  - We have previously shown that hydrogen peroxide (H(2)O(2)) upregulates
      endothelial nitric oxide synthase (eNOS) expression via a calcium/calmodulin
      dependent protein kinase II (CaMKII)-mediated mechanism whereas it also acutely
      activates eNOS enzyme. We hypothesized that oscillatory shear stress (OSS), which
      stimulates endogenous H(2)O(2), would have effects on eNOS expression and
      function similar to that of exogenous H(2)O(2). Exposure of bovine aortic
      endothelial cells to OSS (+/-15 dynes/cm(2)) increased eNOS mRNA expression by 3
      fold. Pretreatment with either polyethylene glycol-catalase (PEG-CAT, a scavenger
      of H(2)O(2)) or KN93, an inhibitor of CaMKII, abolished this response. OSS
      activated CaMKII in an H(2)O(2)-dependent fashion whereas unidirectional laminar
      shear stress (LSS) inhibited CaMKII phosphorylation. Inhibition of c-Src
      (essential for LSS upregulation of eNOS) had no effect on OSS upregulation of
      eNOS. Additionally, OSS stimulated NO* production acutely. Scavenging of H(2)O(2)
      by PEG-CAT attenuated OSS stimulation of NO* by 50% whereas it had no effect on
      LSS regulation of NO* production. These data suggest that intracellular H(2)O(2)
      and CaMKII mediate OSS upregulation of eNOS. The acute activation of eNOS by OSS
      also partially requires H(2)O(2). As OSS has been shown previously to stimulate
      sustained production of superoxide (O(2)*-) which would inactivate NO*, these
      responses may represent attempted compensation to restore NO* bioavailability in
      areas exposed to OSS. Simultaneous stimulation of O(2)*- and NO* by this
      mechanism, however, could facilitate peroxynitrite formation and protein
      nitration, which may enhance atherosclerotic lesion formation. Both OSS and LSS
      upregulate eNOS expression but via different signaling mechanisms.

PMID- 15242743
TI  - Cholinergic-adrenergic antagonism in the induction of tachyarrhythmia by
      electrical stimulation in isolated rat atria.
AB  - Atrial tachyarrhythmias (AT) are the most common cardiac rhythm disturbance. In
      the present study, we analyzed the cholinergic-adrenergic interaction in the in
      vitro induction of cholinergic-dependent tachyarrhythmia by high-frequency
      electric stimulation. Tachyarrhythmia was evoked in isolated rat right atria by
      trains of electric stimuli. Atrial response was expressed as the tachyarrhythmia
      induction index (ATI, i.e. the fraction of applied trains that resulted in
      arrhythmia induction). ATI was reversibly increased by 0.6 microM carbachol
      (CCh), which also decreased atrial spontaneous rate (ASR). In contrast, 10 nM
      isoproterenol (ISO), 100 microM tyramine and the phosphodiesterase inhibitor
      isobutyl-methylxanthine (IBMX, 100 microM) increased ASR and decreased ATI.
      Amiodarone (AMI, 10 microM) reduced ATI in the presence and absence of CCh.
      Further CCh addition restored ATI in atria treated with either IBMX or AMI, but
      not when both compounds were present. Increase in ATI by CCh in atria pretreated
      with IBMX plus ISO was significantly attenuated by 3 mM NaF. The antagonism
      between cholinergic muscarinic and beta-adrenergic receptor stimulation (the
      former facilitating and the latter inhibiting tachyarrhythmia installation)
      possibly involves regulation of the phosphorylation status of adenosine cyclic 3'
      5'-monophosphate (cAMP)-dependent protein kinase substrates. Additionally, cAMP
      independent, AMI-sensitive mechanism stimulated by CCh (possibly muscarinic
      dependent K(+) current activation) seems to contribute to AT facilitation.

PMID- 15242744
TI  - Semliki Forest virus is an efficient and selective vector for gene delivery in
      infarcted rat heart.
AB  - Gene therapy is emerging as a realistic addition to the therapeutic arsenal in
      heart failure, but the search for suitable vectors for cardiac transfection is
      still ongoing. In this study, we explore the applicability of recombinant Semliki
      Forest virus (SFV) in heart failure. SFV was intracoronarily delivered 2 weeks
      after induction of myocardial infarction in the rat model for heart failure.
      Duration of SFV expression was determined, and tissue distribution was studied by
      histochemical, biochemical, and reverse transcriptase-polymerase chain reaction
      (RT-PCR) analyses. Expression of SFV-mediated transfection in the heart reached
      its maximum after 48-72 h and subsided within a week. Intracoronary
      administration of SFV efficiently transfected the non-infarcted cardiac wall,
      resulting in high levels of beta-galactosidase (beta-gal) activity (1337 +/- 537
      IU/mg) and lacZ RNA in the hearts of all rats, whereas brain, kidney, liver,
      lung, spleen, and testis were lacZ negative. In conclusion, intracoronarily
      delivered SFV has a favourable distribution pattern, showing expression of the
      transgene restricted to the heart.

PMID- 15242745
TI  - Effect of bullfrog LH and FSH on newt testes under different temperatures.
AB  - Environmental temperature plays important roles for amphibian gonadal function.
      In this study, we examined the responses of testicular tissue of adult male newts
      (Cynops pyrrhogaster) to amphibian gonadotropins both in vitro and in vivo under
      different temperatures. When minced testes were incubated in vitro at different
      temperatures (8-37 degrees C) under an atmosphere of 95% O(2)-5% CO(2) for 3h
      with bullfrog luteinizing hormone (LH) or follicle-stimulating hormone (FSH), LH
      stimulated testosterone production more than FSH. The testosterone production
      increased as the incubation temperature increased. Hypophysectomized newts were
      injected with bullfrog LH or FSH and maintained at 8 or 18 degrees C. In the 18
      degrees C group, the testicular weight of the hypophysectomized control decreased
      when compared with that of with the intact control. The testicular weight of the
      LH-treated hypophysectomized group decreased more than that of the
      hypophysectomized control, indicating that LH induced the evacuation of mature
      spermatozoa from the testes of LH-treated hypophysectomized newts. In the FSH
      treated newts, the testicular weight was greater than that in the
      hypophysectomized control, and was maintained at a value similar to that of the
      intact control. In the 8 degrees C group, there was no significant difference in
      testicular size among the intact control, hypophysectomized control, and FSH
      treated newts. LH strongly induced spermiation as it did at 18 degrees C. The
      plasma testosterone level in the hypophysectomized newts decreased dramatically,
      but LH was effective in restoring it. Its effect was more potent at 8 degrees C
      than at 18 degrees C. On the other hand, FSH did not induce a significant
      increase in the plasma testosterone levels at either temperatures. The results
      indicate a temperature-dependent difference in responsiveness of the testis both
      in vitro and in vivo to LH and FSH.

PMID- 15242746
TI  - Hormone release is tied to changes in cell size in the osmoreceptive prolactin
      cell of a euryhaline teleost fish, the tilapia, Oreochromis mossambicus.
AB  - Prolactin (PRL) cells from a teleost fish, the tilapia, Oreochromis mossambicus,
      facilitate the direct study of osmoreception. The release of two prolactins,
      PRL(188) and PRL(177), which act in freshwater osmoregulation in teleost fish,
      rises in vitro within 5 min after extracellular osmolality falls. An increase in
      cell size accompanied this rise. Cell size and PRL release also increased, albeit
      more slowly, following the partial replacement of medium NaCl (55 mOsmolal) with
      an equivalent concentration of urea, a membrane-permeant molecule. Similar
      replacement using mannitol, which is membrane-impermeant, elicits no response.
      These findings suggest that osmoreception is linked to changes in cell volume
      rather than to extracellular osmolality per se.

PMID- 15242747
TI  - Hormonal influence on amylase gene expression during Seabass (Lates calcarifer)
      larval development.
AB  - alpha-Amylase gene expression was detected in newly hatched seabass (Lates
      calcarifer) larvae and peaked at around first feeding. This suggests a greater
      importance of carbohydrates during early larval development than might be
      expected for carnivorous fishes. In vivo cortisol and triiodothyronine (T(3))
      treatment of seabass larvae upregulated alpha-amylase gene expression. The
      identification of a functional glucocorticoid-response element (GRE) on the
      amylase gene promoter indicates that cortisol (glucocorticoid) stimulation of
      amylase gene expression is direct via GRE. However no TRE (thyroid-response
      element) was found on the amylase gene and its promoter, and various
      concentrations of T(3) (1nM-10microM) also did not induce alpha-amylase gene
      promoter activity in rat AR42-J cells transfected with the promoter construct,
      unlike dexamethasone treatment. This suggests that T(3) stimulation of amylase
      gene expression in vivo was indirect, probably secondary to its promotion of one
      or more developmental processes.

PMID- 15242748
TI  - Reproductive activity in captive female Honey possums, Tarsipes rostratus,
      assessed by faecal steroid analysis.
AB  - Hormonal changes associated with reproductive activity in the unique pollen and
      nectar-feeding marsupial Honey possum, Tarsipes rostratus, have been monitored by
      the measurement of sex steroids excreted via the faeces. From a radio-metabolism
      study, 63% of administered [(14)C]oestradiol was excreted in the faeces and 37%
      via the urine. Peak levels in the faeces were reached 6h after injection and by a
      mean 12h, 95% of steroid was eliminated. The principal metabolic products of
      progesterone that were identified by chromatographic analysis were the isomers
      5alpha- and 5beta-pregnan-3beta-ol-20-one with only trace amounts of progesterone
      and the isomers 5beta-pregnan-3beta,20beta- and 20alpha-diols. Extended excretory
      profiles for faecal progestagens (PM) and oestradiol-17beta (E(2)) are reported
      for the first time in a marsupial. The profiles from 4 females held in indoor
      cages with an artificial photoperiod suggest that long days inhibit reproductive
      activity in this species, as is the case in a number of other marsupials. One
      female appeared to resume cycling after a 5-month period and the time between
      peak levels of both E(2) and PM suggest that the length of the oestrous cycle in
      the Honey possum is approximately 25 days. The PM profile suggests that the
      corpora lutea secrete low levels of progesterone for approximately the first 19
      days after ovulation, followed by increased rates of excretion during the final 6
      days.

PMID- 15242749
TI  - Growth hormone differentially regulates muscle myostatin1 and -2 and increases
      circulating cortisol in rainbow trout (Oncorhynchus mykiss).
AB  - Myostatin (MSTN) negatively regulates muscle growth in vertebrates. Salmonids
      produce two myostatin transcripts from separate genes. Surprisingly, quantitative
      analyses indicate different regulatory mechanisms for the two myostatin genes in
      rainbow trout. MSTN1 mRNA levels were elevated 26% following recombinant bovine
      growth hormone (rbGH) treatment, while MSTN2 mRNA levels were reduced 74%
      compared to controls. MSTN precursor protein (42kDa) levels were elevated in rbGH
      treated fish compared to controls. In addition, circulating cortisol levels were
      elevated 71% following rbGH treatment compared to controls. In treated and
      control fish, cortisol levels were elevated 245% at day 0 compared to subsequent
      days. Treated fish exhibited cortisol levels 207% higher than controls at 0.5
      day, and remained at least 50% higher for 7 days following treatment. This
      pattern of change was positively correlated to MSTN1 mRNA levels. This is the
      first time a direct relationship has been reported between GH, cortisol, and
      myostatin. In addition, following rbGH administration, myosin protein
      concentrations in skeletal muscle samples increased, suggesting that GH regulates
      expression of the most abundant muscle protein. These results indicate the two
      myostatin genes are differentially regulated and may possess different functions
      in rainbow trout muscle, and suggests a possible interaction between GH,
      cortisol, and muscle growth.

PMID- 15242750
TI  - Sexual differentiation traits in functional males with female genital apertures
      (male symbol fga) in the woodlice Armadillidium vulgare Latr. (Isopoda,
      Crustacea).
AB  - This study reports the results of examination of the gonadal morphology and
      ultrastructural features of the androgenic hormone (AH)-producing androgenic
      gland cells of laboratory stocks of functional male woodlice, Armadillidium
      vulgare, with female genital apertures ( male symbol fga), with and without
      experimentally induced infections of the sex-ratio-distorting endobacterial
      parasite, Wolbachia. Males ( male symbol fga) have been reported in wild
      populations containing individuals infected with this maternally transmitted sex
      ratio-distorting parasite. We report a reduction of testicular segment (utricle)
      number, androgenic gland cell hypertrophy, and electron-dense ultrastructural
      cytological features in male symbol fga males. The presence of the Wolbachia
      parasite had no effect on the features we examined. These results suggest that
      male symbol fga males are produced as the result of a delayed expression/action
      of the male sex-determining AH which causes a "lag-phase" delay in male
      differentiation in genetic males and is not due to the presence, in genetic
      females, of a hypothetical, epigenetic "M" gene as suggested by Rigaud and
      Juchault. Our results favor the interpretation of males as true genetic (ZZ)
      males in which the delayed AH action appears to involve cellular AH trafficking
      pathways which may be controlled by an impaired autosomal gene responsible for AH
      action.

PMID- 15242751
TI  - Structural determination and histochemical localization of ghrelin in the red
      eared slider turtle, Trachemys scripta elegans.
AB  - We purified ghrelin peptide and determined the cDNA sequence encoding the
      precursor protein from the stomach of the red-eared slider turtle, Trachemys
      scripta elegans. The Trachemys ghrelin is comprised of 25-amino acids and has the
      sequence GSSFLSPEYQNTQQRKDPKKHTKLN. The third serine residue was modified by n
      octanoic (C8:0), decanoic (C10:0) or unsaturated decanoic acid (C10:1). The
      carboxyl-terminal end of the peptide was not amidated, as seen in the ghrelins of
      other land vertebrates. Quantitative real-time PCR analysis revealed high levels
      of gene expression in the stomach and moderate levels in the large intestine and
      pancreas. Histochemical studies of turtle stomach revealed that ghrelin
      immunopositive (ghrelin-ip) cells, which were small and round, were observed in
      the mucosal layer of the stomach but not in the myenteric plexus, and ghrelin
      mRNA-expressing (ghrelin-ex) cells detected by in situ hybridization were
      scattered in a similar distribution as ghrelin-ip cells. These results indicate
      that ghrelin is present in reptiles.

PMID- 15242752
TI  - Environmental estrogens can affect the function of mussel hemocytes through rapid
      modulation of kinase pathways.
AB  - Estrogens and estrogenic chemicals can affect several vertebrate non-reproductive
      functions, the immune response in particular. We have previously shown that in
      the hemocytes of the marine mollusc Mytilus the natural estrogen 17beta-estradiol
      (E(2)) can affect the immune function through rapid tyrosine kinase-mediated
      signalling pathways converging on phosphorylation of both mitogen activated
      protein kinases (MAPKs) and signal transducers and activators of transcription
      (STATs), whose activation plays a key role in the immune response. In this work
      the effects of synthetic estrogens (such as DES), estrogenic chemicals (such as
      Bisphenol A, Nonylphenol), and plant estrogens (genistein) on mussel hemocytes
      were evaluated. The results demonstrate that all the EDCs tested exert in vitro
      effects similar to those of E(2) on lysosomal membrane stability, although at
      concentrations 1000 times higher than those of the natural estrogen. When the
      effects of DES, BPA, and NP on tyrosine kinase-mediated cell signalling were
      investigated, estrogenic compounds showed distinct effects on the phosphorylation
      state of MAPK and STAT members. In particular, only DES, like E(2), induced p38
      MAPK phosphorylation, whereas BPA and NP seem to have opposite effects. Moreover,
      different EDCs significantly decreased the tyrosine phosphorylation state of
      STAT3 and STAT5, showing a distinct effect with respect to E(2). Experiments with
      specific kinase inhibitors showed that activation of p38 MAPK, but also of ERK
      MAPK and PI3-kinase, plays a key role in mediating the effect of DES. On the
      other hand, the effects of NP were partly mediated by ERK MAPK activation. BPA
      induced lysosomal membrane destabilisation was unaffected by either MAPK or PI3-K
      inhibitors. However, hemocyte pre-treatment with the PKC inhibitor GF109203X
      prevented the effects of both BPA and NP, this indicating that kinase pathways
      other than those involving MAPKs are also responsible for mediating the effects
      of certain EDCs. Overall, the results support the hypothesis that EDCs may
      rapidly modulate the function of mussel hemocytes through activation of
      transduction pathways involving different kinase-mediated cascades. Moreover, the
      effects of EDCs on the phosphorylation state of transcription factor STATs
      suggest that these compounds may lead to changes in gene expression secondary to
      modulation of kinase/phosphatases. Our data address to the importance of
      investigating full range responses to estrogenic chemicals and may help
      understanding their basic mechanisms of action in ecologically relevant
      invertebrate species.

PMID- 15242753
TI  - Molecular characterization of the leopard gecko POMC gene and expressional change
      in the testis by acclimation to low temperature and with a short photoperiod.
AB  - The gene for proopiomelanocortin (POMC), a common precursor of malanotropins,
      corticotropin, and beta-endorphin, was isolated and analyzed in the squamata
      species, the leopard gecko, Eublepharis macularius. Leopard gecko POMC (lgPOMC)
      cDNA is composed of 1299bp, excluding the poly(A) tail, and encodes 270 amino
      acids. The deduced amino acid sequence showed the same structural organization as
      that of other species and displayed identity with those of other vertebrates: 68%
      with mud turtles, 57/57% with African clawed frog A/B, 53% with chickens, and 45%
      with mice. In a phylogenic tree, the lgPOMC clustered with the sequences of the
      mud turtle POMC and python POMC. The lgPOMC gene comprises three exons and two
      introns and this structure is consistent with humans, rats, mice, African clawed
      frog and zebrafish. RT-PCR analysis revealed that the lgPOMC mRNA was expressed
      only in the whole brain, pituitary, and gonads. To analyze in more detail, a
      competitive assay system to quantify the expression levels of POMC mRNA was
      established. We measured the POMC mRNA expression levels in the leopard gecko
      testes following transfer from a condition of 29 degrees C, 16L/8D to 18 degrees
      C, 10L/14D over 6 weeks. This 6-week acclimation increased the POMC mRNA
      expression levels significantly. This suggests that the leopard gecko POMC
      derived peptides play a role in the mediation of the effect of environmental
      factors on reproduction.

PMID- 15242754
TI  - Molecular cloning and expression of preproadrenomedullin gene from common carp
      Cyprinus carpio L.
AB  - A preproadrenomedullin (preproAM) gene was isolated from common carp Cyprinus
      carpio L. by PCR mediated homology cloning. The isolated gene was composed of
      516bp, which translated to a protein having 171 amino acid residues. The signal
      peptide was composed of 23 amino acid residues and predicted adrenomedullin (AM)
      was conserved in this sequence and made up of 49 amino acid residues. AM gene
      from carp shared identities of 64.0, 44.2, and 46.0% to takifugu (AM-1), human,
      and rat AM orthologues, respectively. The analysis of genomic structure revealed
      that carp preproAM gene is spread over two exons interrupted by one intron
      (92bp). AM genes clustered together and carp AM gene showed similarity to
      takifugu AM-1 gene according to the phylogenetic analysis. Expression analysis
      revealed that carp AM gene expressed constitutively in all the organs confirmed.
      Moreover, we demonstrated that expression of carp AM gene increased by treatment
      of LPS or hydrocortisone in different tissues by quantitative real-time PCR.

PMID- 15242755
TI  - Cloning and tissue distribution of the chicken type 2 corticotropin-releasing
      hormone receptor.
AB  - We report the cloning of the complete coding sequence of the putative chicken
      type 2 corticotropin-releasing hormone receptor (CRH-R2) by rapid amplification
      of cDNA ends (RACE). The chicken CRH-R2 is a 412-amino acid 7-transmembrane G
      protein-coupled receptor, showing 87% identity to the Xenopus laevis and
      Oncorhynchus keta CRH-R2s, and 78-80% to mammalian CRH-R2s. The distribution of
      CRH-R2 mRNA was studied by RT-PCR analysis and compared to CRH-R1 distribution.
      Both CRH-R1 and CRH-R2 mRNA are expressed in the main chicken brain parts. In
      peripheral organs, CRH-R1 mRNA shows a more restricted distribution, whereas CRH
      R2 mRNA is expressed in every tissue investigated, indicating that a number of
      actions of CRH and/or CRH-like peptides remain to be discovered in the chicken as
      well as in other vertebrates.

PMID- 15242756
TI  - Connexin 26-mediated gap junctional intercellular communication suppresses
      paracellular permeability of human intestinal epithelial cell monolayers.
AB  - In some cell types, gap junctional intercellular communication (GJIC) is
      associated with tight junctions. The present study was performed to determine the
      roles of GJIC in regulation of the barrier function of tight junctions. Caco-2
      human colonic cells were used as a monolayer model, and barrier function was
      monitored by measuring mannitol permeability and transepithelial electrical
      resistance (TER). The monolayers were chemically disrupted by treatment with
      oleic acid and taurocholic acid. Western blotting analyses were performed to
      evaluate the protein levels of connexins, which are components of gap junctional
      intercellular channels. Cx26 expression was detected in preconfluent Caco-2
      cells, and its level increased gradually after the monolayer reached confluency.
      These results prompted us to examine whether overexpression of Cx26 affects
      barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed
      significantly lower mannitol permeability and higher TER than mock transfectants
      when the monolayers were chemically disrupted. The levels of claudin-4, an
      important component of tight junctions, were significantly increased in the
      stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play
      a crucial role in enhancing the barrier function of Caco-2 cell monolayers.

PMID- 15242758
TI  - Telomere length mediates the effects of telomerase on the cellular response to
      genotoxic stress.
AB  - Telomerase inhibition may be a novel anti-cancer strategy that can be used in
      combination with conventional therapies, such as DNA damaging agents. There are
      conflicting reports as to whether and to what extent telomerase and telomere
      length influence the sensitivity of cells to genotoxins. To understand the
      relationship between telomere length, telomerase expression, and sensitivity to
      genotoxic stress, we expressed the catalytic subunit of telomerase, hTERT, in
      human fibroblasts having different telomere lengths. We show that telomerase
      confers resistance to ionizing radiation, bleomycin, hydrogen peroxide, and
      etoposide only in cells with short, presumably near-dysfunctional, telomeres.
      This resistance depended on the ability of telomerase to elongate the short
      telomeres, and telomerase did not protect cells with long telomeres.
      Interestingly, although long telomeres had no effect on sensitivity to etoposide
      and bleomycin, they exacerbated sensitivity to hydrogen peroxide, supporting the
      idea that, compared to other types of DNA damage, telomeres are particularly
      vulnerable to oxidative damage. Our findings identify a mechanism and conditions
      under which telomerase and telomeres affect the response of human cells to
      genotoxic agents and may have important implications for anti-cancer
      interventions.

PMID- 15242757
TI  - BRCA1 185delAG mutation inhibits Akt-dependent, IAP-mediated caspase 3
      inactivation in human ovarian surface epithelial cells.
AB  - BRCA1 mutations have long been associated with altered apoptosis. We have
      recently reported that caspase 3 activation is increased in human ovarian surface
      epithelial (OSE) cells expressing a germline N-terminal BRCA1 185delAG mutation.
      Here, we report increased caspase 3 activity in 185delAG OSE cells associated
      with decreased expression of cIAP-1 and X-linked inhibitor of apoptosis (XIAP),
      and decreased ubiquitination of caspase 3. Overexpression of XIAP restored active
      caspase 3 ubiquitination and lowered levels of caspase 3 activity. Further, the
      BRCA1 185delAG mutation was associated with reduced levels of phosphorylated
      Akt1. Transfection with activated Akt1 led to increased cIAP-1 and XIAP levels
      similar to that seen in BRCA1 185delAG cell lines. Taken together, these data
      suggest a direct link between the BRCA1 185delAG mutation and alterations in the
      caspase-mediated apoptotic pathway.

PMID- 15242759
TI  - Interaction of the disintegrin and cysteine-rich domains of ADAM12 with integrin
      alpha7beta1.
AB  - We describe a novel interaction between the disintegrin and cysteine-rich (DC)
      domains of ADAM12 and the integrin alpha7beta1. Integrin alpha7beta1 extracted
      from human embryonic kidney 293 cells transfected with alpha7 cDNA was retained
      on an affinity column containing immobilized DC domain of ADAM12. 293 cells
      stably transfected with alpha7 cDNA adhered to DC-coated wells, and this adhesion
      was partially inhibited by 6A11 integrin alpha7 function-blocking antibody. The
      X1 and the X2 extracellular splice variants of integrin alpha7 supported equally
      well adhesion to the DC protein. Integrin alpha7beta1-mediated cell adhesion to
      DC had different requirements for Mn2+ than adhesion to laminin. Furthermore,
      integrin alpha7beta1-mediated cell adhesion to laminin, but not to DC, resulted
      in efficient cell spreading and phosphorylation of focal adhesion kinase (FAK) at
      Tyr397. We also show that adhesion of L6 myoblasts to DC is mediated in part by
      the endogenous integrin alpha7beta1 expressed in these cells. Since integrin
      alpha7 plays an important role in muscle cell growth, stability, and survival,
      and since ADAM12 has been implicated in muscle development and regeneration, we
      postulate that the interaction between ADAM12 and integrin alpha7beta1 may be
      relevant to muscle development, function, and disease. We also conclude that
      laminin and the DC domain of ADAM12 represent two functional ligands for integrin
      alpha7beta1, and adhesion to each of these two ligands via integrin alpha7beta1
      triggers different cellular responses.

PMID- 15242760
TI  - Prosaposin: a new player in cell death prevention of U937 monocytic cells.
AB  - We report that prosaposin binds to U937 and is active as a protective factor on
      tumor necrosis factor alpha (TNFalpha)-induced cell death. The prosaposin-derived
      saposin C binds to U937 cells in a concentration-dependent manner, suggesting
      that prosaposin behaves similarly. Prosaposin binding induces U937 cell death
      prevention, reducing both necrosis and apoptosis. This effect was inhibited by
      mitogen-activated protein ERK kinase (MEK) and sphingosine kinase (SK)
      inhibitors, indicating that prosaposin prevents cell apoptosis by activation of
      extracellular signal-regulated kinases (ERKs) and sphingosine kinase. Prosaposin
      led to rapid ERK phosphorylation in U937 cells as detected by anti-phospho-p44/42
      mitogen-activated protein (MAP) kinase and anti-phosphotyrosine reactivity on ERK
      immunoprecipitates. It was partially prevented by apo B-100 and pertussis toxin
      (PT), suggesting that both lipoprotein receptor-related protein (LRP) receptor
      and Go-coupled receptor may play a role in the prosaposin-triggered pathway.
      Moreover, sphingosine kinase activity was increased by prosaposin treatment as
      demonstrated by the enhanced intracellular formation of sphingosine-1-phosphate
      (S-1-P). The observation that the phosphatidylinositol 3-kinase (PI3K) inhibitor
      wortmannin prevented the prosaposin effect on cell apoptosis suggests that
      sphingosine kinase exerts its anti-apoptotic activity by the PI3K-Akt pathway.
      Thus, cell apoptosis prevention by prosaposin occurs through ERK phosphorylation
      and sphingosine kinase. The biological effect triggered by prosaposin might be
      extended to primary cells because it triggers Erk phosphorylation in peripheral
      blood mononuclear cells (PBMCs). This is the first evidence of a biological
      effect consequent to a signal transduction pathway triggered by prosaposin in
      cells of non-neurological origin.

PMID- 15242761
TI  - m-Calpain implication in cell cycle during muscle precursor cell activation.
AB  - Milli-calpain, a member of the ubiquitous cysteine protease family, is known to
      control late events of cell-cell fusion in skeletal muscle tissue through its
      involvement in cell membrane and cytoskeleton component reorganization. In this
      report, we describe the characterization of m-calpain compartmentalization and
      activation during the initial steps of muscle precursor cell recruitment and
      differentiation. By immunofluorescence analysis, we show that m-calpain is
      present throughout the cell cycle in the nucleus of proliferating myoblast C2
      cells. However, when myoblasts enter a quiescent/G0 stage, m-calpain staining is
      detected only in the cytoplasm. Moreover, comparison of healthy and injured
      muscle shows distinct m-calpain localization in satellite stem cells. Indeed, m
      calpain is not found in quiescent satellite cells, but following muscle injury,
      when satellite cells start to proliferate, m-calpain appears in the nucleus. To
      determine the implication of m-calpain during the cell cycle progression,
      quiescent myoblasts were forced to re-enter the cell cycle in the presence or not
      of the specific calpain inhibitor MDL 28170. We demonstrate that this calpain
      inhibitor blocks the cell cycle, prevents accumulation of MyoD in the G1 phase
      and enhances Myf5 expression. These data support an important new role for m
      calpain in the control of muscle precursor cell activation and thus suggest its
      possible implication during the initial events of muscle regeneration.

PMID- 15242762
TI  - PML-nuclear bodies accumulate DNA in response to polyomavirus BK and simian virus
      40 replication.
AB  - Promyelocytic nuclear bodies (PML-NBs) are distinct nuclear structures that are
      involved in apoptosis, differentiation, transcriptional regulation and DNA damage
      response. These bodies have also been shown to associate with nuclear sites of
      viral DNA replication. In the present study, we used BrdU pulse labeling to
      demonstrate that PML-NBs accumulate newly synthesized DNA in cells infected by
      the polyomaviruses simian virus 40 (SV40) or polyomavirus BK (BKV). Sequestration
      of DNA molecules in these structures depended on active viral DNA replication,
      and was observed exclusively in cells that contained prominent viral replication
      domains. Furthermore, a significant portion of the accumulated DNA was found to
      be single-stranded, indicating that the sequestered DNA had been subjected to
      processing by nuclease or DNA unwinding activities. siRNA-mediated suppression of
      the PML protein prevented the recruitment of single-stranded DNA into nuclear
      foci, but did not significantly affect the overall efficiency of viral DNA
      replication. These results indicate a role of PML and PML-NBs in post-replication
      DNA processing, and suggest that PML-NBs become linked to sites of viral DNA
      synthesis due to a role of these structures in DNA metabolism.

PMID- 15242763
TI  - Newcastle disease virus neuraminidase primes neutrophils for stimulation by
      galectin-3 and formyl-Met-Leu-Phe.
AB  - Human neutrophils are activated by the beta-galactoside-binding lectin galectin
      3, provided that the cells are primed by in vivo extravasation or by in vitro
      preactivation with, for example, LPS. Removal of terminal sialic acid can change
      neutrophil functionality and responsiveness due to exposure of underlying
      glycoconjugate receptors or change in surface charge. Here, we investigated
      whether such alteration of the cell surface carbohydrate composition can alter
      the responsiveness of the cells to galectin-3. Neutrophils were treated with
      neuraminidases (NA) of different origins: Clostridium perfringens (CP),
      Salmonella typhimurium, Vibrio cholerae, and Newcastle disease virus (NDV). In
      the presence of NDV-NA, but no other NA, the otherwise non-responding neutrophils
      responded readily to galectin-3 by activation of the NADPH-oxidase. The galectin
      3 priming effect was inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N
      acetyl-neuraminic acid. Earlier studies have shown that priming of the neutrophil
      response to galectin-3 with, for example, LPS is paralleled by degranulation of
      intracellular vesicles and granules and upregulation of potential galectin-3
      receptors. Also, NDV-NA (but not CP-NA) treatment induced degranulation, shown as
      an upregulation of complement receptor 3. Since not only the galectin response
      but also the response to the chemoattractant fMLF was primed, NDV-NA appears to
      induce a general priming phenomenon, possibly due to receptor upregulation by
      degranulation.

PMID- 15242764
TI  - Endogenously released Smac is insufficient to mediate cell death of human lung
      carcinoma in response to etoposide.
AB  - Cytotoxic agents eliminate tumor cells via different mechanisms including
      apoptosis, although this process is not equally efficient in all kinds of cancer
      cells. Thus, small cell lung carcinomas (SCLCs) are more sensitive than non-small
      cell lung carcinomas (NSCLCs) to therapy-induced killing. During apoptosis,
      several apoptogenic proteins release from the mitochondria. Among these proteins
      is Smac/DIABLO. Overexpression of Smac effectively potentiates apoptosis by
      neutralizing the caspase-inhibitory function of the inhibitors of apoptosis
      proteins (IAPs). However, the physiological relevance of endogenously released
      Smac in the promotion of malignant cell death is still unclear. Analysis of a
      panel of human lung cancer cell lines revealed that there is no altered Smac
      expression in NSCLC and SCLC that might initially impair the drug-induced cell
      death. Upon engagement of the mitochondrial pathway of apoptosis, etoposide
      provoked cytosolic accumulation of Smac along with cytochrome c and loss of the
      mitochondrial membrane potential. Most of these events as well as nuclear
      apoptotic changes required caspase activation in SCLC, but not in NSCLC.
      Unexpectedly, pan-caspase inhibition had no effect on Smac release. Co-treatment
      of SCLC with the IAP-binding peptide Smac-N7 enhanced etoposide-induced apoptosis
      in a concentration-dependent manner, whereas Smac downregulation by small
      interfering RNA (siRNA) did not influence caspase-3/-7 activities, nuclear
      morphological changes, DNA fragmentation, and plasma membrane integrity. Release
      of cytochrome c and mitochondrial protease Omi/HtrA2 is still detectable at these
      conditions. These data suggest that Smac deficiency may be compensated for by
      action of redundant determinants to kill cancer cells. Thus, translocation of
      endogenous Smac into cytosol does not play a critical role in cell death of human
      lung carcinoma after etoposide treatment.

PMID- 15242765
TI  - The abnormal spindle protein is required for germ cell mitosis and oocyte
      differentiation during Drosophila oogenesis.
AB  - In this study, we present evidence that the asp function is required in oogenesis
      for germline cell divisions as well as for cyst polarity and oocyte
      differentiation. Consistent with previously described roles in spindle
      organization during Drosophila meiosis and mitosis, asp mutation leads to severe
      defects in spindle microtubule organization within the germarium. The mitotic
      spindles of the mutant cystocytes are composed by wavy microtubules and have
      abnormal poles that often lack gamma-tubulin. The fusome structure is also
      compromised. In the absence of asp function, the cystocyte divisions fail
      resulting in egg chamber with fewer than 16 germ cells. Moreover, the microtubule
      network within the developing germline cysts may assemble incorrectly in turn
      affecting the microtubule based transport of the specific determinants that is
      required during mid-oogenesis for the oocyte differentiation program.

PMID- 15242766
TI  - Interaction of cortactin and Arp2/3 complex is required for sphingosine-1
      phosphate-induced endothelial cell remodeling.
AB  - Sphingosine-1-phosphate (S1P) induces capillary formation of endothelial cells on
      Matrigel in accompany with actin assembly and accumulation of cortactin and
      Arp2/3 complex at the cell-leading edge. Suppression of cortactin expression with
      a cortactin antisense oligo significantly impaired S1P-induced capillary
      formation, migration of endothelial cells, and actin assembly at the cell
      periphery. Overexpression of wild-type cortactin tagged by green fluorescent
      protein (GFP) increased the S1P-induced tube formation and cell motility, whereas
      the cells overexpressing the mutant formed poorly capillary network and became
      less motile in response to S1P. Analysis of distribution in Triton X-100
      insoluble fractions demonstrated that the cortactin mutant inhibited the
      association of wild-type cortactin and Arp2/3 complex with the actin-enriched
      complex. Furthermore, actin polymerization at and distribution of Arp2/3 complex
      as well as endogenous cortactin into the cell-leading edge mediated by S1P was
      disturbed. These data suggest that the interaction between cortactin and Arp2/3
      complex plays an important role in S1P-mediated remodeling of endothelial cells.

PMID- 15242767
TI  - DNA methylation control of tissue polarity and cellular differentiation in the
      mammary epithelium.
AB  - Alterations in gene expression accompany cell-type-specific differentiation. In
      complex systems where functional differentiation depends on the organization of
      specific cell types into highly specialized structures (tissue morphogenesis), it
      is not known how epigenetic mechanisms that control gene expression influence
      this stepwise differentiation process. We have investigated the effect of DNA
      methylation, a major epigenetic pathway of gene silencing, on the regulation of
      mammary acinar differentiation. Our in vitro model of differentiation encompasses
      human mammary epithelial cells that form polarized and hollow tissue structures
      (acini) when cultured in the presence of basement membrane components. We found
      that acinar morphogenesis was accompanied with chromatin remodeling, as shown by
      alterations in histone 4 acetylation, heterochromatin 1 protein, and histone 3
      methylated on lysine 9, and with an increase in expression of MeCP2, a mediator
      of DNA-methylation-induced gene silencing. DNA hypomethylation induced by
      treatment with 5-aza-2' deoxycytidine during acinar differentiation essentially
      prevented the formation of apical tissue polarity. This treatment also induced
      the expression of CK19, a marker of cells that are in a transitional
      differentiation stage. These results suggest that DNA methylation is a mechanism
      by which mammary epithelial differentiation is coordinated both at the tissue and
      cellular levels.

PMID- 15242768
TI  - Functional interaction between nuclear matrix-associated HBXAP and NF-kappaB.
AB  - Hepatitis B virus X-associated protein (HBXAP) is a plant homeodomain (PHD)
      finger-containing protein implicated in transcription regulation. However, the
      underlying molecular mechanism remains to be defined. Here, we show that HBXAP
      represses NF-kappaB-mediated gene activation in a dose-dependent manner. Our
      results showed that HBXAP and NF-kappaB colocalize to the nuclear matrix with
      specific physical interaction between them. HBXAP may depend on its nuclear
      matrix localization for its repression of NF-kappaB-mediated gene repression. A
      specific nuclear matrix targeting sequence of HBXAP was identified. The sequence
      is included in a region encompassing amino acids 688-722 that could form a coiled
      coil structure. The 18-amino acid stretch lies at the core of that structure. The
      present results showed that either the coiled-coil conformation or the PHD finger
      domain is crucial for the transcription repression activity of HBXAP on NF-kappaB
      mediated gene activation. Taken together, our results suggest that HBXAP may
      function as a negative regulator for TNF-alpha-induced, NF-kappaB-mediated gene
      activation.

PMID- 15242769
TI  - Demystifying SP cell purification: viability, yield, and phenotype are defined by
      isolation parameters.
AB  - Side population (SP) cells isolated from bone marrow, skeletal muscle, and skin
      have been shown to engraft in dystrophic muscle. However, there have been
      questions on the phenotypical heterogeneity, tissue of origin, and relationships
      among SP cell populations extracted from different tissues. Studies on bone
      marrow SP cells have followed a consistent protocol for their isolation and
      results obtained are concordant. In contrast, protocols for the isolation of
      muscle SP cells vary greatly, and consequently reports on their phenotype,
      differentiation potential and origin have been inconsistent. To address this
      controversy, we demonstrate that isolation parameters, such as tissue
      dissociation, cell counting, Hoechst concentration, and stringency in the
      selection of SP cells, have an effect on the yield, viability, and homogeneity of
      SP cells derived from bone marrow, skeletal muscle, and skin. In this paper, we
      demonstrate that SP cells isolated from the bone marrow are distinct from SP
      cells extracted from skeletal muscle and skin tissues. This study offers an
      explanation for the controversy surrounding muscle SP cells, provides a detailed
      standardized protocol for their isolation, and highlights basic guidelines for
      reproducible and reliable isolation of SP cells from any tissue.

PMID- 15242770
TI  - Erythropoietin-dependent autocrine secretion of tumor necrosis factor-alpha in
      hematopoietic cells modulates proliferation via MAP kinase--ERK-1/2 and does not
      require tyrosine docking sites in the EPO receptor.
AB  - Primary erythroid cells and erythroid cell lines may synthesize and secrete tumor
      necrosis factor-alpha (TNF-alpha) following stimulation with erythropoietin
      (EPO). The effect of triggering TNF-alpha synthesis and secretion was
      investigated in erythroleukemia and myeloid cell lines: HCD57, DA3-EPOR, and BAF3
      EPOR. The EPO-induced, membrane-bound form of autocrine TNF-alpha seemed to
      enhance proliferation of HCD57 and DA3-EPOR cells; however, the concentration of
      secreted autocrine/paracrine TNF-alpha was never sufficient to have an effect.
      Autocrine TNF-alpha acts through TNFRII receptors to stimulate proliferation.
      Modulation of mitogen-activated protein kinase (MAPK)/extracellular signal
      related kinase (ERK-1/2) activity by the membrane-bound form of autocrine TNF
      alpha apparently played a central role in the control of EPO-dependent
      proliferation of HCD57 and DA3-EPOR cells. Primary erythroid cells and DA3-EPOR
      cells were found to express similar, high levels of both TNFRI and TNFRII,
      showing that differential expression of TNF-alpha receptors does not explain why
      primary cells are inhibited and DA3-EPOR cells are stimulated by autocrine TNF
      alpha. BAF3 cells expressing a mutant EPOR with no cytoplasmic tyrosine residues
      were capable of triggering EPO-dependent TNF-alpha synthesis and secretion,
      indicating that tyrosine-docking sites in the EPOR were not required for EPO
      dependent TNF-alpha secretion.

PMID- 15242771
TI  - Akt is a major angiogenic mediator downstream of the Ang1/Tie2 signaling pathway.
AB  - Tie2 and VEGF receptors (VEGFRs) are tyrosine kinases that play essential roles
      in angiogenesis. Activation of both receptors leads to the activation of Akt, an
      important mediator of cell survival and cell motility. In this study, we compared
      the role of Akt in Tie2-mediated versus VEGF-mediated endothelial cell (EC)
      survival and EC sprouting. Our data show that Akt is required and sufficient to
      mediate Ang1-induced EC survival in response to growth factor depletion. Blocking
      Akt function abolishes angiopoietin 1 (Ang1), a ligand for Tie2, mediated EC
      survival, and activating Akt rescues a Tie2 blockade-induced EC apoptosis. In
      contrast, activating Akt rescues EC apoptosis induced by a VEGF blockade, but
      interestingly, blocking Akt function has no effects on VEGF-induced EC survival,
      demonstrating that Akt is sufficient but not required for VEGF-mediated EC
      survival. In addition, we show that both Ang1 and VEGF induce EC sprouting in a
      three-dimensional collagen gel, which depends on the activation of Akt. Blocking
      Akt action inhibited EC sprouting induced by Ang1 or VEGF. Therefore, the data
      show that Akt is the primary mediator of Ang1-induced EC survival while multiple
      pathways are involved downstream of VEGF responsible for EC survival. However,
      Akt is required and sufficient to mediate the EC sprouting induced by both Ang1
      and VEGF.

PMID- 15242772
TI  - Tumor cell locomotion: differential dynamics of spontaneous and induced migration
      in a 3D collagen matrix.
AB  - Although great strides have recently been made in elucidating the factors
      initiating tumor cell migration and the relevant cellular pathways involved, the
      constituent components of migratory dynamics for individual tumor cell motion
      have still not been resolved. Utilizing a three-dimensional (3D) collagen assay
      and computer-assisted, continuous single cell tracking, we investigated the basic
      parameters for both the spontaneous and norepinephrine-induced migration of
      highly metastatic MBA-MB-468 breast, PC-3 prostate, and SW 480 colon carcinoma
      cells. We show that tumor cells do not migrate with uniform migrational structure
      and speed as previously thought, but rather, the induction of locomotion elicits
      significant increases in speed, break frequency, and total cell displacement, but
      decreases in break length and no change in the recruitment of nonlocomotory
      cells. We furthermore illustrate the corresponding morphological changes of
      induced tumor cell migration with emphasis on motion in a collagen matrix. These
      results demonstrate the complexity of tumor cell migration, and the compulsion
      for incorporating not only knowledge of intracellular pathways, but also
      fundamental parameters of migratory behavior into any expansive theory of tumor
      cell migration and metastasis formation. We furthermore establish the analytical
      methodology of investigating both the stimulation and potential pharmaceutical
      inhibition of tumor cell migration.

PMID- 15242773
TI  - Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent
      phenotype and cell cycle arrest in normal human diploid fibroblasts.
AB  - Exposure of WI38 human diploid fibroblasts (HDFs) to hydrogen peroxide (H2O2)
      induced premature senescence. The senescent HDFs were permanently arrested and
      exhibited a senescent phenotype including enlarged and flattened cell morphology
      and increased senescence-associated beta-galactosidase (SA-beta-gal) activity.
      The induction of HDF senescence was associated with an activation of p53,
      increased expression of p21Cip1/WAF1, and hypophosphorylation of retinoblastoma
      protein (Rb), while no changes in the expression of p16Ink4a, p27Kip1, and p14Arf
      were observed. Exposure of WI38 cells to H2O2 also selectively activated
      phosphatidylinostol 3-kinase (PI3 kinase) and mitogen-activated protein kinase
      (MAPK) kinase (MEK), while no changes in p38 MAPK and Jun kinase (JNK) activities
      were observed. Selective inhibition of PI3 kinase activity with LY294002
      abrogated H2O2-induced cell enlargement and flattened morphology and
      significantly attenuated the increase in SA-beta-gal activity, but did not affect
      H2O2-induced cell cycle arrest. In contrast, selective inhibition of MEK and p38
      MAPK with PD98059 and SB203580, respectively, produced no significant effect on
      H2O2-induced senescent phenotype and cell cycle arrest. These findings
      demonstrate that expression of the senescent phenotype can be uncoupled from cell
      cycle arrest in prematurely senescent cells induced by H2O2 and does not
      contribute to the maintenance of permanent cell cycle arrest.

PMID- 15242774
TI  - Interferon induces the interaction of prothymosin-alpha with STAT3 and results in
      the nuclear translocation of the complex.
AB  - Interferons (IFNs) play critical roles in host defense by modulating the
      expression of various genes via tyrosine phosphorylation of STAT transcription
      factors. Many cytokines including IFNs induce tyrosine phosphorylation of the
      STAT3 transcription factor, which regulates acute phase gene expression. Using
      the yeast two-hybrid interaction trap, in which a tyrosine kinase is introduced
      into the yeast to allow tyrosine phosphorylation of bait proteins, prothymosin
      alpha (ProTalpha) was identified to interact with the amino terminal half of
      tyrosine-phosphorylated STAT3. ProTalpha is a small, acidic, extremely abundant,
      and essential protein that may play a role in chromatin remodeling, and has been
      implicated in regulating the growth and survival of mammalian cells. Besides the
      interaction of tyrosine-phosphorylated STAT3 with ProTalpha in yeast cells, IFN
      induced the interaction of ProTalpha with STAT3 in mammalian cells, and this
      interaction was dependent on the tyrosine phosphorylation of STAT3. Moreover,
      IFNalpha induces the translocation of STAT3 and ProTalpha from the cytoplasm to
      the nucleus where these proteins colocalize. Since ProTalpha has an extremely
      strong nuclear localization and STAT proteins apparently lack any nuclear
      localization signals, the association of STAT3 with ProTalpha may provide a
      mechanism to result in STAT localization in the nucleus.

PMID- 15242775
TI  - Galphaq/11 signaling induces apoptosis through two pathways involving reduction
      of Akt phosphorylation and activation of RhoA in HeLa cells.
AB  - We have previously reported that expression of the constitutively active mutant
      of Galpha11 or stimulation of m1 muscarinic acetylcholine receptor induced
      proteolytic activation of Rho-associated kinase (ROCK-I) by caspase and apoptosis
      in HeLa cells. In this study, we investigate the molecular mechanisms of
      Galphaq/11-induced apoptosis in m1 muscarinic acetylcholine receptor-expressing
      HeLa cells. Overexpression of Bcl-2 inhibited carbachol-induced ROCK-I cleavage,
      indicating a mitochondrial apoptotic pathway. Overexpression of the
      constitutively active mutant of Akt that delivers an anti-apoptotic survival
      signal had a similar influence. Insulin, a major survival factor in many cells,
      strongly increased phosphorylation of Akt, which was completely blocked by
      carbachol. This latter effect was partially inhibited by treatment with the
      tyrosine phosphatase inhibitors, orthovanadate and pervanadate. In parallel with
      these observations, carbachol attenuated insulin-stimulated tyrosine
      phosphorylation of insulin receptor substrate-1, an effect eliminated by
      orthovanadate. On the other hand, carbachol induced rapid stimulation of
      endogenous RhoA, and expression of a constitutively active mutant of RhoA
      increased ROCK-I cleavage. Orthovanadate and the dominant negative mutant of RhoA
      partially, and their combination completely, inhibited carbachol-induced ROCK-I
      cleavage and apoptosis. These results demonstrate that Gq/11 signaling induces
      apoptosis by reducing insulin-stimulated Akt phosphorylation through tyrosine
      dephosphorylation and activating RhoA in HeLa cells.

PMID- 15242776
TI  - Complexes of gamma-tubulin with nonreceptor protein tyrosine kinases Src and Fyn
      in differentiating P19 embryonal carcinoma cells.
AB  - Nonreceptor protein tyrosine kinases of the Src family have been shown to play an
      important role in signal transduction as well as in regulation of microtubule
      protein interactions. Here we show that gamma-tubulin (gamma-Tb) in P19 embryonal
      carcinoma cells undergoing neuronal differentiation is phosphorylated and forms
      complexes with protein tyrosine kinases of the Src family, Src and Fyn. Elevated
      expression of both kinases during differentiation corresponded with increased
      level of proteins phosphorylated on tyrosine. Immunoprecipitation experiments
      with antibodies against Src, Fyn, gamma-tubulin, and with anti-phosphotyrosine
      antibody revealed that gamma-tubulin appeared in complexes with these kinases. In
      vitro kinase assays showed tyrosine phosphorylation of proteins in gamma-tubulin
      complexes isolated from differentiated cells. Pretreatment of cells with Src
      family selective tyrosine kinase inhibitor PP2 reduced the amount of
      phosphorylated gamma-tubulin in the complexes. Binding experiments with
      recombinant SH2 and SH3 domains of Src and Fyn kinases revealed that protein
      complexes containing gamma-tubulin bound to SH2 domains and that these
      interactions were of SH2-phosphotyrosine type. The combined data suggest that Src
      family kinases might have an important role in the regulation of gamma-tubulin
      interaction with tubulin dimers or other proteins during neurogenesis.

PMID- 15242777
TI  - Pyrrolidine dithiocarbamate and zinc inhibit proteasome-dependent proteolysis.
AB  - Proteasomes play important roles in a variety of cellular processes such as cell
      cycle progression, signal transduction and immune responses. Proteasome activity
      is important in maintaining rapid turnover of short-lived proteins, as well as
      preventing accumulation of misfolded or damaged proteins. Alteration in ubiquitin
      proteasome function may be detrimental to its crucial role in maintaining
      cellular homeostasis. Here, we have found that treatment of pyrrolidine
      dithiocarbamate (PDTC), a zinc ionophore, resulted in the accumulation of several
      proteasome substrates including p53 and p21 in HeLa cells. The PDTC effect was
      due to an extended half-life of these proteins through the mobilization of zinc.
      PDTC and/or zinc also increased fluorescence intensity of Ub(G76V)-GFP fusion
      protein that is degraded rapidly by the ubiquitin-proteasome system. Treatment of
      cells with zinc induced formation of ubiquitinated inclusions in the centrosome,
      a histological marker of proteasome inhibition. Western blotting showed zinc
      induced increase in laddering bands of polyubiquitin-conjugated proteins. In
      vitro study, zinc inhibited the ubiquitin-independent proteasomal degradations of
      p21 and alpha-synuclein. These results suggest that zinc may modulate cell
      functions through its action on the turnover of proteins that are susceptible to
      proteasome-dependent proteolysis.

PMID- 15242778
TI  - The suppressor of cytokine signaling (SOCS)-7 interacts with the actin
      cytoskeleton through vinexin.
AB  - To understand the function of the suppressor of cytokine signaling (SOCS)-7, we
      have looked for proteins interacting with SOCS-7 in a stringent yeast two-hybrid
      screen of a human leukocyte cDNA-library. We identified the cytoskeletal molecule
      vinexin as a partner interacting with SOCS-7. Tests with deletion mutants of SOCS
      7 demonstrated that a central region of the molecule containing several proline
      rich regions, N-terminal to the SH2 domain, was responsible for the binding to
      vinexin. It is thus likely that one of the SH3 domains of vinexin interacts with
      a poly-proline region of SOCS-7. The interaction with vinexin was confirmed
      biochemically as vinexin-alpha was co-precipitated with SOCS-7. Confocal laser
      scanning microscopy in HEK293T, MCF-7, and 3T3-L1 cells showed that part of the
      transfected SOCS-7-green fluorescent protein (GFP) molecules merged with vinexin
      and with actin. Taken together, our data indicate that SOCS-7 interacts with
      vinexin and the actin cytoskeleton.

PMID- 15242779
TI  - In vitro assembly properties of mutant and chimeric intermediate filament
      proteins: insight into the function of sequences in the rod and end domains of
      IF.
AB  - The factors and mechanisms regulating assembly of intermediate filament (IF)
      proteins to produce filaments with their characteristic 10 nm diameter are not
      fully understood. All IF proteins contain a central rod domain flanked by
      variable head and tail domains. To elucidate the role that different domains of
      IF proteins play in filament assembly, we used negative staining and electron
      microscopy (EM) to study the in vitro assembly properties of purified bacterially
      expressed IF proteins, in which specific domains of the proteins were either
      mutated or swapped between a cytoplasmic (mouse neurofilament-light (NF-L)
      subunit) and nuclear intermediate filament protein (human lamin A). Our results
      indicate that filament formation is profoundly influenced by the composition of
      the assembly buffer. Wild type (wt) mouse NF-L formed 10 nm filaments in assembly
      buffer containing 175 mM NaCl, whereas a mutant deleted of 18 NH2-terminal amino
      acids failed to assemble under similar conditions. Instead, the mutant assembled
      efficiently in buffers containing CaCl2 > or = 6 mM forming filaments that were
      10 times longer than those formed by wt NF-L, although their diameter was
      significantly smaller (6-7 nm). These results suggest that the 18 NH2-terminal
      sequence of NF-L might serve two functions, to inhibit filament elongation and to
      promote lateral association of NF-L subunits. We also demonstrate that
      lengthening of the NF-L rod domain, by inserting a 42 aa sequence unique to
      nuclear IF proteins, does not compromise filament assembly in any noticeable way.
      Our results suggests that the known inability of nuclear lamin proteins to
      assemble into 10 nm filaments in vitro cannot derive solely from their longer rod
      domain. Finally, we demonstrate that the head domain of lamin A can substitute
      for that of NF-L in filament assembly, whereas substitution of both the head and
      tail domains of lamins for those of NF-L compromises assembly. Therefore, the
      effect of lamin A "tail" domain alone, or the synergistic effect of lamin "head"
      and the "tail" domains together, interferes with assembly into 10-nm filaments.

PMID- 15242780
TI  - Epigenetic activation of the 5-hydroxytryptamine (serotonin) receptor 2C in
      embryonal carcinoma cells is DNA replication-dependent.
AB  - The epigenetic states of key regulatory genes must be altered to drive cell fate
      decisions in differentiating cells. This process must be coupled, at least
      transiently, to the DNA replication machinery. Only a few genes, however, have
      been shown to require DNA replication for their activation or repression upon
      induction of differentiation. We have developed a methodology for examining how
      gene expression is coupled to cell division during the early stages of
      differentiation of embryonal carcinoma (EC) cells. Using this approach, we find
      that the expression of the 5-hydroxytryptamine (serotonin) receptor 2C (Htr2c) is
      strongly increased in the second division after all-trans retinoic acid addition.
      We propose that the epigenetic activation of Htr2c in EC cells results from a
      chromatin remodeling process that requires at least two passages through S phase.

PMID- 15242781
TI  - Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids.
AB  - Polysialic acid (polySia) is a unique and highly regulated posttranslational
      modification of the neural cell adhesion molecule (NCAM). The presence of polySia
      affects NCAM-dependent cell adhesion and plays an important role during brain
      development, neural regeneration and plastic processes including learning and
      memory. Polysialylated NCAM is expressed on several neuroendocrine tumors of high
      malignancy and correlates with poor prognosis. Two closely related enzymes, the
      polysialyltransferases ST8SiaII and ST8SiaIV, catalyze the biosynthesis of
      polySia. However, the impact of each enzyme in NCAM polysialylation is not
      understood. Here, we describe the selective cell-based in vitro inhibition of
      ST8SiaII using synthetic sialic acid precursors. We provide evidence for
      different substrate affinities of ST8SiaII and ST8SiaIV. These data open the
      possibility to study the individual role of the two enzymes during various
      aspects of brain development and function and in tumorigenesis.

PMID- 15242782
TI  - Subcellular localization of A and B Nm23/NDPK subunits.
AB  - The human Nm23-H1/NDPK A and Nm23-H2/NDPK B encode for two subunits of nucleoside
      diphosphate kinase--a ubiquitous enzyme that transfers the terminal phosphates
      from ATP to (d)NDPs. Although having an 88% amino acid sequence identity and an
      already assigned biochemical role in the cell, the two subunits appear to have
      additional and distinctive cell functions. In particular, both subunits have been
      reported to be involved in tumor progression and metastasis. The aim of this
      study was to determine the specific, and potentially distinct, localizations of
      both subunits in tumor cells of different origin and differentiation and
      therefore to search for a possible link between their localization and the stage
      of disease. We used the GFP reporter system to analyze the ectopic expression of
      GFP-Nm23 proteins in head and neck tumor cell lines by fluorescent microscopy
      techniques. Our experiments revealed that GFP-fused Nm23-H1 and -H2 proteins
      display the same localization in transfected cells, regardless of their origin
      and differentiation status. The proteins are principally found in the cytosol and
      the endoplasmic reticulum. Moreover, some cells exhibit nuclear staining, which
      appears to be cell cycle-dependent.

PMID- 15242783
TI  - Evidence for disulfide involvement in the regulation of intramolecular autolytic
      processing by human adamalysin19/ADAM19.
AB  - Human adamalysin 19 (a disintegrin and metalloproteinase 19, hADAM19) is
      activated by furin-mediated cleavage of the prodomain followed by an autolytic
      processing within the cysteine-rich domain at Glu586-Ser587, which occurs
      intramolecularly, producing an NH2 terminal fragment (N-fragment) associated with
      its COOH-terminal fragment (C-fragment), most likely through disulfide bonds.
      When stable Madin-Darby canine kidney (MDCK) transfectants overexpressing soluble
      hADAM19 were treated with dithiothreitol (DTT) or with media at pH 6.5, 7.5, or
      8.5, the secretion and folding of the enzyme were not affected. Autolytic
      processing was blocked by DTT and pH 6.5 media, which favor disulfide reduction,
      but was increased by pH 8.5 media, which promotes disulfide formation. Cys605,
      Cys633, Cys639, and Cys643 of the C-fragment appear to be partially responsible
      for the covalent association between the C-fragment and the N-fragment. A new
      autolytic processing site at Lys543-Val544 was identified in soluble mutants when
      these cysteine residues were individually mutated to serine residues. Shed
      fragments were also detectable in the media from MDCK cells stably expressing the
      full-length Cys633Ser mutant. Ilomastat/GM6001 inhibited hADAM19 with an IC50 of
      447 nM, but scarcely affected the shedding process. The cysteine-rich domain
      likely forms disulfide bonds to regulate the autolytic processing and shedding of
      hADAM19.

PMID- 15242784
TI  - PAF is involved in the Mycoplasma arthritidis superantigen-triggering pathway for
      iNOS and COX-2 expression in murine peritoneal cells.
AB  - We investigated the capacity of Mycoplasma arthritidis mitogen (MAM) to induce
      (a) expression of the inducible enzymes cyclo-oxygenase (COX-2) and nitric oxide
      synthase (iNOS), (b) production of prostaglandin E2 (PGE2) and nitric oxide (NO),
      and (c) involvement of platelet-activating factor (PAF) in the MAM-induced
      activation pathway. Resident peritoneal cells from C3H/HePas mice were incubated
      with MAM in the presence or absence of a PAF-antagonist (WEB2170) or COX-2
      inhibitors (nimesulide or NS398). Enzyme expression was evaluated by
      immunoblotting, PGE2 by EIA, and NO by Griess reaction. Following MAM-stimulation
      of peritoneal cells, expression of COX-2 was detected at 3 h (peak levels at 12
      h) and of iNOS at 6 h (peak levels at 20 h). PGE2 increased till 20 h, decreasing
      thereafter, whereas NO increased with time. WEB2170 (5 x 10(-5) M) treatment
      caused 44% inhibition of NO output and reduced iNOS expression (48% at the peak
      of expression). Concomitant treatment with WEB2170 and nimesulide (10(-5) M)
      reversed these inhibitory effects. WEB2170 reduced COX-2 expression (43% at the
      peak of expression) and prevented the decline in PGE2 levels after 20 h. These
      results suggest the involvement of PAF in the signaling pathway triggered by MAM
      that leads to expression of iNOS and COX-2, and show that PAF regulates the
      production of NO, possibly by controlling levels of PGE2.

PMID- 15242785
TI  - Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen.
AB  - Tenascin-X (TNX) is an extracellular matrix glycoprotein. We previously
      demonstrated that TNX regulates the expression of type VI collagen. In this
      study, we investigated the binding of TNX to type I collagen as well as to type
      VI collagen and the effects of these proteins on fibrillogenesis of type I
      collagen. Full-length recombinant TNX, which is expressed in and purified from
      mammalian cell cultures, and type VI collagen purified from bovine placenta were
      used. Solid-phase assays revealed that TNX or type VI collagen bound to type I
      collagen, although TNX did not bind to type VI collagen, fibronectin, or laminin.
      The rate of collagen fibril formation and its quantity, measured as increased
      turbidity, was markedly increased by the presence of TNX, whereas type VI
      collagen did not increase the quantity but accelerated the rate of collagen
      fibril formation. Combined treatment of both had an additive effect on the rate
      of collagen fibril formation. Furthermore, deletion of the epidermal growth
      factor-like (EGF) domain or fibrinogen-like domain of TNX attenuated the initial
      rate of collagen fibril formation. Finally, we observed abnormally large collagen
      fibrils by electron microscopy in the skin from TNX-deficient (TNX-/-) mice
      during development. These findings demonstrate a fundamental role for TNX and
      type VI collagen in regulation of collagen fibrillogenesis in vivo and in vitro.

PMID- 15242786
TI  - ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome
      alignment and meiotic spindle organization in metaphase II stage mouse oocytes.
AB  - ATRX is a centromeric heterochromatin binding protein belonging to the SNF2
      family of helicase/ATPases with chromatin remodeling activity. Mutations in the
      human ATRX gene result in X-linked alpha-thalassaemia with mental retardation
      (ATRX) syndrome and correlate with changes in methylation of repetitive DNA
      sequences. We show here that ATRX also functions to regulate key stages of
      meiosis in mouse oocytes. At the germinal vesicle (GV) stage, ATRX was found
      associated with the perinucleolar heterochromatin rim in transcriptionally
      quiescent oocytes. Phosphorylation of ATRX during meiotic maturation is dependent
      upon calcium calmodulin kinase (CamKII) activity. Meiotic resumption also
      coincides with deacetylation of histone H4 at lysine 5 (H4K5 Ac) while ATRX and
      histone H3 methylated on lysine 9 (H3K9) remained bound to the centromeres and
      interstitial regions of condensing chromosomes, respectively. Inhibition of
      histone deacetylases (HDACs) with trichostatin A (TSA) disrupted ATRX binding to
      the centromeres of hyperacetylated chromosomes resulting in abnormal chromosome
      alignments at metaphase II (MII). Similarly, while selective ablation of ATRX by
      antibody microinjection and RNA interference (RNAi) had no effect on the
      progression of meiosis, it had severe consequences for the alignment of
      chromosomes on the metaphase II spindle. These results suggest that genome-wide
      epigenetic modifications such as global histone deacetylation are essential for
      the binding of ATRX to centromeric heterochromatin. Moreover, centromeric ATRX is
      required for correct chromosome alignment and organization of a bipolar meiotic
      metaphase II spindle.

PMID- 15242787
TI  - Fertilization stimulates long-lasting oscillations of CaMKII activity in mouse
      eggs.
AB  - Elucidation of the biochemical mechanisms by which specific proteins transduce
      the all important intracellular calcium (Ca2+) signal at fertilization into
      events of egg activation will increase our understanding of the regulation of the
      onset of development and the extent to which these signals can be experimentally
      modified. Previously, we reported data supporting the hypothesis that mouse eggs
      have the capability to generate oscillations of the activity of Ca2+ and
      calmodulin-dependent kinase II (CaMKII), regulating the cell cycle and secretion.
      This study directly demonstrates transient increases of enzyme activity in
      relatively close synchrony with Ca2+ oscillations for the first hour of
      fertilization in single mouse eggs monitored for both Ca2+ and CaMKII activity.
      The extent of the enzyme activity increase was correlated with the level of
      intracellular Ca2+. After a rise in activity, the decrease in activity did not
      appear to be due to negative feedback from elevated Ca2+ or CaMKII activity over
      time, since enzyme activity persisted after 8 min of elevated Ca2+ from 7%
      ethanol activation. The contribution of CaMKII from a single sperm to the rise in
      CaMKII activity at fertilization appeared to be negligible. Also, long-term cell
      cycle inhibition was observed in fertilized eggs with the CaMKII antagonist
      myrAIP (50 microM), which did not inhibit the first large Ca2+ transient or
      subsequent early oscillations but did reduce the percentage of eggs fertilized.
      Thus, mammalian eggs appear to drive many activation events over time to
      completion with repeated short bursts of Ca2+ oscillation-dependent CaMKII
      activity, rather than by a steady-state, continuously elevated level of CaMKII
      activity that is maintained by periodic Ca2+ oscillations.

PMID- 15242788
TI  - Fertilization and InsP3-induced Ca2+ release stimulate a persistent increase in
      the rate of degradation of cyclin B1 specifically in mature mouse oocytes.
AB  - Vertebrate oocytes proceed through meiosis I before undergoing a cytostatic
      factor (CSF)-mediated arrest at metaphase of meiosis II. Exit from MII arrest is
      stimulated by a sperm-induced increase in intracellular Ca2+. This increase in
      Ca2+ results in the destruction of cyclin B1, the regulatory subunit of cdk1 that
      leads to inactivation of maturation promoting factor (MPF) and egg activation.
      Progression through meiosis I also involves cyclin B1 destruction, but it is not
      known whether Ca2+ can activate the destruction machinery during MI. We have
      investigated Ca2+ -induced cyclin destruction in MI and MII by using a cyclin B1
      GFP fusion protein and measurement of intracellular Ca2+. We find no evidence for
      a role for Ca2+ in MI since oocytes progress through MI in the absence of
      detectable Ca2+ transients. Furthermore, Ca2+ increases induced by photorelease
      of InsP3 stimulate a persistent destruction of cyclin B1-GFP in MII but not MI
      stage oocytes. In addition to a steady decrease in cyclin B1-GFP fluorescence,
      the increase in Ca2+ stimulated a transient decrease in fluorescence in both MI
      and MII stage oocytes. Similar transient decreases in fluorescence imposed on a
      more persistent fluorescence decrease were detected in cyclin-GFP-injected eggs
      undergoing fertilization-induced Ca2+ oscillations. The transient decreases in
      fluorescence were not a result of cyclin B1 destruction since transients
      persisted in the presence of a proteasome inhibitor and were detected in controls
      injected with eGFP and in untreated oocytes. We conclude that increases in
      cytosolic Ca2+ induce transient changes in autofluorescence and that the pattern
      of cyclin B1 degradation at fertilization is not stepwise but exponential.
      Furthermore, this Ca2+ -induced increase in degradation of cyclin B1 requires
      factors specific to mature oocytes, and that to overcome arrest at MII, Ca2+ acts
      to release the CSF-mediated brake on cyclin B1 destruction.

PMID- 15242789
TI  - A new role for BMP5 during limb development acting through the synergic
      activation of Smad and MAPK pathways.
AB  - In an attempt to identify new genes implicated in the control of programmed cell
      death during limb development, we have generated a cDNA library from the
      regressing interdigital tissue of chicken embryos. We have analyzed 804 sequences
      from this library and identified 23 genes involved in apoptosis in different
      models. One of the genes that came up in the screening was the Bone Morphogenetic
      Protein family member, Bmp5, that has not been previously involved in the control
      of apoptosis during limb development. In agreement with a possible role in the
      control of cell death, Bmp5 exhibited a regulated pattern of expression in the
      interdigital tissue. Transcripts of Bmp5 and BMP5 protein were abundant within
      the cytoplasm of the fragmenting apoptotic interdigital cells in a way suggesting
      that delivery of BMPs into the tissue is potentiated during apoptosis. Gain-of
      function experiments demonstrated that BMP5 has the same effect as other
      interdigital BMPs inducing apoptosis in the undifferentiated mesoderm and growth
      in the prechondrogenic mesenchyme. We have characterized both Smad proteins and
      MAPK p38 as intracellular effectors for the action of BMPs in the developing limb
      autopod. Activation of Smad signaling involves the receptor-regulated genes Smad1
      and -8, and the inhibitory Smad6, and results in both the upregulation of gene
      transcription and protein phosphorylation with subsequent nuclear translocation.
      MAPK p38 is also quickly phosphorylated after BMP stimulation in the limb
      mesoderm. Treatment with the inhibitor of p38, SB203580, revealed that there are
      interdigital genes induced by BMPs in a p38-dependent manner (DKK, Snail and
      FGFr3), and genes induced in a p38-independent manner (BAMBI, Msx2 and Smads).
      Together, our results suggest that Smad and MAPK pathways act synergistically in
      the BMP pathway controlling limb development.

PMID- 15242790
TI  - Choroideremia gene product affects trophoblast development and vascularization in
      mouse extra-embryonic tissues.
AB  - Choroideremia (CHM) is a hereditary eye disease caused by mutations in the X
      linked CHM gene. Disruption of the Chm gene in mice resulted in prenatal death of
      Chm-/Y males and Chm-/Chm+ females that had inherited the mutation from their
      mothers. Male chimeras and Chm+/Chm- females with paternal transmission of the
      mutation were viable and had photoreceptor degeneration reminiscent of human
      choroideremia. Here, we show that Chm-/Y males and Chm-/Chm+ females were
      retarded at e7.5 and died before e11.5 due to multiple defects of the extra
      embryonic tissues. Mutant embryos exhibited deficiency of diploid trophoblasts
      associated with overabundance of giant cells. In yolk sac and placenta, severe
      defects in vasculogenesis were obvious. Chm-/Y males exhibited more pronounced
      phenotypes than Chm-/Chm+ females. The lethal genotypes could be rescued by
      tetraploid aggregation. Chm-/Chm+ females, but not Chm-/Y males, could also be
      rescued when their Chm+/Chm- mothers were mated with Mus spretus males. Backcross
      analysis suggested that the viability of interspecies hybrid Chm-/Chm+ females
      may be due to expression from the Chm allele on the M. spretus X-chromosome
      rather than a modifier effect. Our results demonstrate that Chm is essential for
      diploid trophoblast development and plays a role in the vascularization in
      placenta and yolk sac.

PMID- 15242791
TI  - XCdh1 is involved in progesterone-induced oocyte maturation.
AB  - The molecular events triggered during progesterone-induced oocyte maturation in
      Xenopus are not well understood. One of the first events is the activation of the
      MAPK cascade and the maturation-promoting factor (MPF). The latter triggers
      meiosis I resumption and meiosis II progression until the metaphase II arrest.
      The release of the metaphase II is mediated by the anaphase-promoting complex
      (APC)-dependent degradation of cyclin B. This degradation activity requires the
      APC activator Cdc20 that activates ubiquitination reactions by recruiting
      substrates to the APC. However, recent reports in different organisms involve
      other APC regulators during different phases of the meiotic cycle. Therefore, we
      investigated the role of another APC regulator, XCdh1 during the G2/M transition
      in meiosis I in the Xenopus oocyte. Here, we report that XCdh1 protein is
      expressed in oocytes. Besides, injection of specific XCdh1 antisense inhibits
      progesterone-induced G2/M transition that can be rescued by adding back the
      purified human Cdh1 protein. On the other hand, ectopic expression of low levels
      of XCdh1 protein has a positive effect on the G2/M transition by facilitating
      this process. Moreover, the sole injection of XCdh1 mRNA triggers Mos protein
      synthesis and biphosphorylation of MAPK in absence of progesterone. Altogether,
      these data show that XCdh1 has a positive role during the G2/M transition in the
      oocyte. According to our results, its role could be independent of the APC.

PMID- 15242792
TI  - Sonic Hedgehog functions by localizing the region of proliferation in early
      developing feather buds.
AB  - Feathers are formed following a series of reciprocal signals between the
      epithelium and the mesenchyme. Initially, the formation of a dense dermis leads
      to the induction of a placode in the overlying ectoderm. The ectoderm
      subsequently signals back to the dermis to promote cell division. Sonic Hedgehog
      (Shh) is a secreted protein expressed in the ectoderm that has previously been
      implicated in mitogenic and morphogenetic processes throughout feather bud
      development. We therefore interfered with Shh signaling during early feather bud
      development and observed a dramatic change in feather form and prominence.
      Surprisingly, outgrowth did occur and was manifest as irregular, fused, and
      ectopic feather domains at both molecular and morphological levels. Experiments
      with Di-I and BrdU indicated that this effect was at least in part caused by the
      dispersal of previously aggregated proliferating dermal cells. We propose that
      Shh maintains bud development by localizing the dermal feather progenitors.

PMID- 15242793
TI  - Role of BMP signaling and the homeoprotein Iroquois in the specification of the
      cranial placodal field.
AB  - Different types of placodes originate at the anterior border of the neural plate
      but it is still an unresolved question whether individual placodes arise as
      distinct ectodermal specializations in situ or whether all or a subset of the
      placodes originate from a common preplacodal field. We have analyzed the
      expression and function of the homeoprotein Iro1 in Xenopus and zebrafish
      embryos, and we have compared its expression with several preplacodal and
      placodal markers. Our results indicate that the iro1 genes are expressed in the
      preplacodal region, being one of the earliest markers for this area. We show that
      an interaction between the neural plate and the epidermis is able to induce the
      expression of several preplacodal markers, including Xiro1, by a similar
      mechanism to that previously shown for neural crest induction. In addition, we
      analyzed the role of BMP in the specification of the preplacodal field by
      studying the expression of the preplacodal markers Six1, Xiro1, and several
      specific placodal markers. We experimentally modified the level of BMP activity
      by three different methods. First, we implanted beads soaked with noggin in early
      neurula stage Xenopus embryos; second, we injected the mRNA that encodes a
      dominant negative of the BMP receptor into Xenopus and zebrafish embryos; and
      third, we grafted cells expressing chordin into zebrafish embryos. The results
      obtained using all three methods show that a reduction in the level of BMP
      activity leads to an expansion of the preplacodal and placodal region similar to
      what has been described for neural crest regions. By using conditional constructs
      of Xiro1, we performed gain and loss of function experiments. We show that Xiro1
      play an important role in the specification of both the preplacodal field as well
      as individual placodes. We have also used inducible dominant negative and
      activator constructs of Notch signaling components to analyze the role of these
      factors on placodal development. Our results indicate that the a precise level of
      BMP activity is required to induce the neural plate border, including placodes
      and neural crest cells, that in this border the iro1 gene is activated, and that
      this activation is required for the specification of the placodes.

PMID- 15242794
TI  - Prenatal exposure to thyroid hormone is necessary for normal postnatal
      development of murine heart and lungs.
AB  - Maternal hypothyroxinemia during early pregnancy poses an increased risk for poor
      neuropsychological development of the fetus. We tested the hypothesis that
      maternal hypothyroidism before the onset of fetal thyroid function also affects
      postnatal development of heart and lungs. This question was addressed in
      transgenic mice that express herpes simplex virus thymidine kinase in their
      thyroidal follicle cells. Treatment with ganciclovir rendered these mice severely
      hypothyroid because viral thymidine kinase converts ganciclovir into a cytotoxic
      nucleoside analog. Since ganciclovir crosses the placenta, it also destroyed the
      thyroid of transgenic embryos while leaving the thyroids of nontransgenic
      littermates unaffected. Hypothyroidism of both mother and fetus did not affect
      prenatal heart and lung development. However, the postnatal switch from beta- to
      alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and
      the increase of SERCA-2a mRNA expression did not occur in the ventricular
      myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact
      thyroid) offspring of hypothyroid mothers. Similarly, postnatal animals of the
      latter two groups retained elevated surfactant protein (SP) A, B, and C mRNA
      levels in their alveolar epithelium. In hypothyroid pups from hypothyroid
      mothers, these changes were accompanied by decreased alveolar septation. Our
      study shows that these effects of maternal hypothyroidism become manifest after
      birth and are aggravated by the concomitant existence of neonatal hypothyroidism.

PMID- 15242795
TI  - Neural cells in the esophagus respond to glial cell line-derived neurotrophic
      factor and neurturin, and are RET-dependent.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is expressed in the
      gastrointestinal tract of the developing mouse and appears to play an important
      role in the migration of enteric neuron precursors into and along the small and
      large intestines. Two other GDNF family members, neurturin and artemin, are also
      expressed in the developing gut although artemin is only expressed in the
      esophagus. We examined the effects of GDNF, neurturin, and artemin on neural
      crest cell migration and neurite outgrowth in explants of mouse esophagus,
      midgut, and hindgut. Both GDNF and neurturin induced neural crest cell migration
      and neurite outgrowth in all regions examined. In the esophagus, the effect of
      GDNF on migration and neurite outgrowth declined with age between E11.5 and
      E14.5, but neurturin still had a strong neurite outgrowth effect at E14.5.
      Artemin did not promote neural migration or neurite outgrowth in any region
      investigated. The effects of GDNF family ligands are mediated by the Ret tyrosine
      kinase. We examined the density of neurons in the esophagus of Ret-/- mice, which
      lack neurons in the small and large intestines. The density of esophageal neurons
      in Ret-/- mice was only about 4% of the density of esophageal neurons in Ret+/-
      and Ret+/+ mice. These results show that GDNF and neurturin promote migration and
      neurite outgrowth of crest-derived cells in the esophagus as well as the
      intestine. Moreover, like intestinal neurons, the development of esophageal
      neurons is largely Ret-dependent.

PMID- 15242796
TI  - En1 and Wnt7a interact with Dkk1 during limb development in the mouse.
AB  - Wnt signaling plays an essential role in induction and development of the limb.
      Missing digits are one consequence of the reduced Wnt signaling in Wnt7a null
      mice, while extra digits result from excess Wnt signaling in mice null for the
      Wnt antagonist Dkk1. The extra digits and expanded apical ectodermal ridge (AER)
      of Dkk1-deficient mice closely resemble En1 null mice. To evaluate the in vivo
      interaction between En1 and the canonical Wnt signaling pathway, we generated
      double and triple mutants combining the hypomorphic doubleridge allele of Dkk1
      with null alleles of En1 and Wnt7a. Reducing Dkk1 expression in Dkk1d/+Wnt7a-/-
      double mutants prevented digit loss, indicating that Wnt7a acts through the
      canonical pathway during limb development. Reducing Dkk1 levels in Dkk1d/dEn1-/-
      double mutants resulted in severe phenotypes not seen in either single mutant,
      including fused bones in the autopod, extensive defects of the zeugopod, and loss
      of the ischial bone. The subsequent elimination of Wnt7a in Dkk1d/dEn1-/-Wnt7a-/-
      triple mutants resulted in correction of most, but not all, of these defects. The
      failure of Wnt7a inactivation to completely correct the limb defects of
      Dkk1d/dEn1-/- double mutants indicates that Wnt7a is not the only gene regulated
      by En1 during development of the mouse limb.

PMID- 15242797
TI  - The cell lineage of the polyplacophoran, Chaetopleura apiculata: variation in the
      spiralian program and implications for molluscan evolution.
AB  - Polyplacophorans, or chitons, are an important group of molluscs, which are
      argued to have retained many plesiomorphic features of the molluscan body plan.
      Polyplacophoran trochophore larvae posses several features that are distinctly
      different from those of their sister trochozoan taxa, including modifications of
      the ciliated prototrochal cells, the postrochal position of the larval eyes or
      ocelli, epidermal calcareous spicules, and a collection of serially reiterated
      epidermal shell plates. Despite these differences, chitons demonstrate a
      canonical pattern of equal spiral cleavage shared by other spiralian phyla that
      permits the identification of homologous cells across this animal clade. Cell
      lineage analysis using intracellular labeling on one chiton species, Chaetopleura
      apiculata, shows that the ocelli are generated from different lineal precursors
      (second-quartet micromeres: 2a, 2c) compared to those in all other spiralians
      studied to date (first-quartet micromeres: 1a, 1c). This situation implies that
      significant changes have also occurred in terms of the inductive interactions
      that control eye development in the spiralians. Although radical departures from
      the spiralian developmental program are seen in some molluscs (i.e.,
      cephalopods), the findings presented here indicate that important changes can
      occur even within the highly constrained framework of the spiral cleavage
      program. Among spiralians, variation has been reported for the origin of the
      anterior, sensory, apical organ, which arises from the 1c and 1d micromeres in C.
      apiculata. The prototroch of C. apiculata consists of two to three irregular rows
      of ciliated cells but arise from 1q and 2q daughters, similar to that of
      Ischnochiton rissoi, as well as the gastropod, Patella vulgata. Despite certain
      early claims, there is no supporting evidence that any of the shell plates arise
      pretrochally in C. apiculata. The first seven of eight definitive shell plates
      that arise in the larva originate from shell secreting grooves in the postrochal
      region (derived from 2c, 2d, 3d). Earlier descriptions indicate that the eighth
      plate arises later at metamorphosis, and as this is formed posteriorly, it too
      forms in the postrochal region. On the other hand, epidermal spicules originate
      from both pretrochal and postrochal cells (1a,1d, 2a, 2c, 3c, 3d). The
      significance of these observations is discussed in light of various hypotheses
      concerning the origin of the conchiferan shell. This study reveals conservation,
      as well as evolutionary novelty, in the assignment of specific cell fates in the
      spiralians.

PMID- 15242798
TI  - The role of Pax2 in mouse inner ear development.
AB  - The paired box transcription factor, Pax2, is important for cochlear development
      in the mouse inner ear. Two mutant alleles of Pax2, a knockout and a frameshift
      mutation (Pax21Neu), show either agenesis or severe malformation of the cochlea,
      respectively. In humans, mutations in the PAX2 gene cause renal coloboma syndrome
      that is characterized by kidney abnormalities, optic nerve colobomas and mild
      sensorineural deafness. To better understand the role of Pax2 in inner ear
      development, we examined the inner ear phenotype in the Pax2 knockout mice using
      paint-fill and gene expression analyses. We show that Pax2-/- ears often lack a
      distinct saccule, and the endolymphatic duct and common crus are invariably
      fused. However, a rudimentary cochlea is always present in all Pax2 knockout
      inner ears. Cochlear outgrowth in the mutants is arrested at an early stage due
      to apoptosis of cells that normally express Pax2 in the cochlear anlage. Lack of
      Pax2 affects tissue specification within the cochlear duct, particularly regions
      between the sensory tissue and the stria vascularis. Because the cochlear
      phenotypes observed in Pax2 mutants are more severe than those observed in mice
      lacking Otx1 and Otx2, we postulate that Pax2 plays a key role in regulating the
      differential growth within the cochlear duct and thus, its proper outgrowth and
      coiling.

PMID- 15242799
TI  - Cardiac neural crest ablation alters Id2 gene expression in the developing heart.
AB  - Id proteins are negative regulators of basic helix-loop-helix gene products and
      participate in many developmental processes. We have evaluated the expression of
      Id2 in the developing chick heart and found expression in the cardiac neural
      crest, secondary heart field, outflow tract, inflow tract, and anterior
      parasympathetic plexus. Cardiac neural crest ablation in the chick embryo, which
      causes structural defects of the cardiac outflow tract, results in a significant
      loss of Id2 expression in the outflow tract. Id2 is also expressed in Xenopus
      neural folds, branchial arches, cardiac outflow tract, inflow tract, and
      splanchnic mesoderm. Ablation of the premigratory neural crest in Xenopus embryos
      results in abnormal formation of the heart and a loss of Id2 expression in the
      heart and splanchnic mesoderm. This data suggests that the presence of neural
      crest is required for normal Id2 expression in both chick and Xenopus heart
      development and provides evidence that neural crest is involved in heart
      development in Xenopus embryos.

PMID- 15242800
TI  - Proteolytic cleavage of the cell surface protein p160 is required for detachment
      of the fertilization envelope in the sea urchin.
AB  - Sea urchin eggs secrete a serine protease activity, CGSP1, at fertilization that
      is essential for the block to polyspermy. Several targets of this proteolytic
      activity on the plasma membrane were identified here using a cell surface
      biotinylation approach. Amino acid microsequencing of one of these proteins led
      to the identification of a 4.75-kb cDNA clone from a Strongylocentrotus
      purpuratus ovary cDNA library that encodes a 160-kDa protein called p160. This
      protein contains five CUB domains and a putative transmembrane domain suggesting
      that p160 is an integral membrane protein with protein-protein interaction motifs
      facing the extracellular matrix of the egg. Whole-mount immunolocalization
      studies demonstrate that p160 is on the surface of the egg, enriched at the tips
      of microvilli. The protein is removed at fertilization in a protease-dependent
      manner, and functional assays suggest that p160 serves to link the plasma
      membrane to the vitelline layer until fertilization. Thus, p160 is a key
      candidate for a vitelline-layer linker protein, the selective proteolysis of
      which functions in the block to polyspermy in the sea urchin egg.

PMID- 15242801
TI  - Gap junctional communication is required to maintain mouse cortical neural
      progenitor cells in a proliferative state.
AB  - The mechanisms that determine whether neural stem cells remain in a proliferative
      state or differentiate into neurons or glia are largely unknown. Here we
      establish a pivotal role for gap junction-mediated intercellular communication in
      determining the proliferation and survival of mouse neural progenitor cells
      (NPCs). When cultured in the presence of basic fibroblast growth factor (bFGF),
      NPCs express the gap junction protein connexin 43 and are dye-coupled. Upon
      withdrawal of bFGF, levels of connexin 43 and dye coupling decrease, and the
      cells cease proliferating and differentiate into neurons; the induction of gap
      junctions by bFGF is mediated by p42/p44 mitogen-activated protein kinases.
      Inhibition of gap junctions abolishes the ability of bFGF to maintain NPCs in a
      proliferative state resulting in cell differentiation or cell death, while
      overexpression of connexin 43 promotes NPC self-renewal in the absence of bFGF.
      In addition to promoting their proliferation, gap junctions are required for the
      survival of NPCs. Gap junctional communication is therefore both necessary and
      sufficient to maintain NPCs in a self-renewing state.

PMID- 15242802
TI  - CiYB1 is a major component of storage mRNPs in ascidian oocytes: implications in
      translational regulation of localized mRNAs.
AB  - In ascidian eggs, the existence of several localized maternal cytoplasmic
      determinants has been proposed and the importance of localized mRNAs for tissue
      differentiation has been demonstrated. We previously identified the ascidian Y
      box proteins (CiYB1, 2 and 3), homologues of which are known to be involved in
      the storage of maternal mRNA in oocytes of other organisms. In this study, we
      found that CiYB1 protein is abundant in the gonad, egg, and embryo. Purification
      of messenger ribonucleoprotein (mRNP) particles from the gonad revealed that
      CiYB1 was one of their major components. A significant change in the distribution
      of CiYB1 protein from stored mRNP particles in the gonad to the ribosome fraction
      in eggs and embryos was observed. This change correlates most likely with the
      shift of stored maternal mRNAs to polyribosomes. Moreover, we found that CiYB1
      colocalized with Cipem and Ci-macho1 mRNAs, which are localized at the posterior
      end of the embryo at the cleavage stage. Cipem and Ci-macho1 mRNAs were co
      immunoprecipitated with CiYB1 in the oocyte and embryo lysates. The formation of
      a complex between Cipem mRNA and CiYB1 protein resulted in translational
      repression in the in vitro translation system. Our results indicate that
      associating with CiYB1 protein contributes to the translational control of the
      localized mRNA in eggs and embryos.

PMID- 15242803
TI  - Structure-function analysis of the Drosophila retinal determination protein
      Dachshund.
AB  - Dachshund (Dac) is a highly conserved nuclear protein that is distantly related
      to the Ski/Sno family of corepressor proteins. In Drosophila, Dac is necessary
      and sufficient for eye development and, along with Eyeless (Ey), Sine oculis
      (So), and Eyes absent (Eya), forms the core of the retinal determination (RD)
      network. In vivo and in vitro experiments suggest that members of the RD network
      function together in one or more complexes to regulate the expression of
      downstream targets. For example, Dac and Eya synergize in vivo to induce ectopic
      eye formation and they physically interact through conserved domains. Dac
      contains two highly conserved domains, named DD1 and DD2, but no function has
      been assigned to either of them in an in vivo context. We performed structure
      function studies to understand the relationship between the conserved domains of
      Dac and the rest of the protein and to determine the function of each domain
      during development. We show that only DD1 is essential for Dac function and while
      DD2 facilitates DD1, it is not absolutely essential in spite of more than 500
      million years of conservation. Moreover, the physical interaction between Eya and
      DD2 is not required for the genetic synergy between the two proteins. Finally, we
      show that DD1 also plays a central role for nuclear localization of Dac.

PMID- 15242804
TI  - Specification of polarity of teloblastogenesis in the oligochaete annelid
      Tubifex: cellular basis for bilateral symmetry in the ectoderm.
AB  - Ectodermal teloblastogenesis in the oligochaete annelid Tubifex is a
      spatiotemporally regulated process that gives rise to four bilateral pairs of
      ectoteloblasts (N, O, P, and Q) that assume distinct fates. Ectoteloblasts on
      either side of the embryo arise from an invariable sequence of asymmetric cell
      divisions of a proteloblast, NOPQ, which occur with a defined orientation with
      respect to the embryonic axes: the N teloblast is generated first and located
      ventralmost, and the Q teloblast, which is generated next, is located dorsalmost;
      finally, the O and P teloblasts are generated by almost equal division of their
      precursor cell, OP. Polarity of teloblastogenesis on one side of the embryo is a
      mirror image of the other; this mirror symmetry of ectoteloblasts about the
      embryo's midline gives rise to the bilaterally symmetric organization of the
      ectoderm. In this study, we examined whether cellular interactions are involved
      in specification of polarity of asymmetric cell divisions in NOPQ cells. A set of
      cell transplantation experiments demonstrated that NOPQ cells are initially
      uncommitted in terms of division pattern and cell fates: If a left NOPQ cell is
      transplanted to the right side of a host embryo, it exhibits a polarity
      comparable to that of right NOPQ cells. The results of another set of cell
      transplantation experiments suggest that contact between NOPQ cells serves as an
      external cue for their polarization, irrespective of their position in the
      embryo, and that in the absence of host NOPQ cells, transplanted NOPQ cells can
      be polarized according to positional information residing in the host embryo. The
      competence of NOPQ cells to respond to external cues tapers down before their
      division into N and OPQ. A set of cell ablation experiments demonstrated that
      neighboring cells such as posteriorly located M teloblasts and anterolaterally
      located micromeres play a role in controlling spatial aspects of NOPQ's behavior
      that gives rise to their division along the dorsoventral axis. These results
      suggest that NOPQ cells, which do not initially have a rigidly fixed polarity,
      become polarized through external cues. Possible sources of signals for this
      polarizing induction are discussed in the light of the present results.

PMID- 15242805
TI  - The C. elegans ezrin-radixin-moesin protein ERM-1 is necessary for apical
      junction remodelling and tubulogenesis in the intestine.
AB  - Members of the ezrin-radixin-moesin (ERM) family of proteins have been found to
      serve as linkers between membrane proteins and the F-actin cytoskeleton in many
      organisms. We used RNA interference (RNAi) approach to assay ERM proteins of the
      Caenorhabditis elegans genome for a possible involvement in apical junction (AJ)
      assembly or positioning. We identify erm-1 as the only ERM protein required for
      development and show, by multiple RNA interference, that additional four-point
      one, ezrin-radixin-moesin (FERM) domain-containing proteins cannot compensate for
      the depletion of ERM-1. ERM-1 is expressed in most if not all cells of the embryo
      at low levels but is upregulated in epithelia, like the intestine. ERM-1 protein
      co-localizes with F-actin and the intermediate filament protein IFB-2 at the
      apical cell cortex. ERM-1 depletion results in intestine-specific phenotypes like
      lumenal constrictions or even obstructions. This phenotype arises after
      epithelial polarization of intestinal cells and can be monitored using markers of
      the apical junction. We show that the initial steps of epithelial polarization in
      the intestine are not affected in erm-1(RNAi) embryos but the positioning of
      apical junction proteins to an apico-lateral position arrests prematurely or
      fails, resulting in multiple obstructions of the intestinal flow after hatching.
      Mechanistically, this phenotype might be due to an altered apical cytoskeleton
      because the apical enrichment of F-actin filaments is lost specifically in the
      intestine. ERM-1 is the first protein of the apical membrane domain affecting
      junction remodelling in C. elegans. ERM-1 interacts genetically with the catenin
      cadherin system but not with the DLG-1 (Discs large)-dependent establishment of
      the apical junction.

PMID- 15242806
TI  - Increased uptake of antisense oligonucleotides by delivery as double stranded
      complexes.
AB  - Antisense oligonucleotides were potentially very powerful tools to modulate gene
      expression. Progress in chemical modification of oligonucleotides to enhance the
      strength and stability of interaction, without loosing specificity, has made the
      antisense strategy very attractive for therapeutic manipulation of the gene
      expression. However, pharmacological applications of oligonucleotides have been
      hindered by the inability to effectively deliver these compounds to their sites
      of action within cells. In this study we evaluated a new concept for antisense
      delivery in cellular systems. We have shown that formation of a duplex between
      the active oligonucleotide (with a chemically modified backbone) and an easily
      degradable complementary oligodeoxynucleotide in the presence of Lipofectamine
      2000 leads to better intracellular uptake and more significant pharmacological
      effect of the active oligonucleotide. To evaluate our approach we targeted the
      MDR1 gene, which coded for P-glycoprotein, a membrane ATPase associated with
      multi-drug resistance in tumor cells. The 2'-O-methyl gapmer antisense RNA
      (active component of the duplex) was complementary to a site flanking the AUG of
      the MDR1 message. Effective inhibition of P-glycoprotein expression was attained
      with sub-micromolar concentrations of duplexes under serum-replete conditions and
      was much stronger than with traditional single stranded antisense delivery. The
      results obtained suggested that double stranded delivery could provide a simple
      and effective means for enhancing cell uptake of pharmacologically active
      oligonucleotides.

PMID- 15242807
TI  - Metformin-induced stimulation of AMP-activated protein kinase in beta-cells
      impairs their glucose responsiveness and can lead to apoptosis.
AB  - Metformin is an anti-diabetic drug that increases glucose utilization in insulin
      sensitive tissues. The effect is in part attributable to a stimulation of AMP
      activated protein kinase (AMPK). The present study demonstrates that metformin
      (0.5-2mM) also dose-dependently activates AMPK in insulin-producing MIN6 cells
      and in primary rat beta-cells, leading to increased phosphorylation of acetyl coA
      carboxylase (ACC). The maximal effect was reached within 12h and sustained up to
      48h. After 24h exposure to metformin (0.5-1mM), rat beta-cells exhibited a
      reduced secretory and synthetic responsiveness to 10mM glucose, which was also
      the case following 24h culture with the AMPK-activator 5-amino-imidazole-4
      carboxamide riboside (AICAR; 1mM). Longer metformin exposure (>24h) resulted in a
      progressive increase in apoptotic beta-cells as was also reported for AICAR;
      metformin-induced apoptosis was reduced by compound C, an AMPK-inhibitor. As with
      AICAR, metformin activated c-Jun-N-terminal kinase (JNK) and caspase-3 prior to
      the appearance of apoptosis. It is concluded that metformin-induced AMPK
      activation in beta-cells reduces their glucose responsiveness and may, following
      sustained exposure, result in apoptosis.

PMID- 15242808
TI  - A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory
      mediators in osteoarthritis.
AB  - ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4
      triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2
      (COX-2) with antiinflammatory activity in animal models. In the present study, we
      investigated the effect of this compound on the production of catabolic or
      antiinflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage
      explants, ITB inhibited the production of prostaglandin E(2) (PGE(2)), tumour
      necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a
      concentration-dependent manner, whereas nitrite was partially reduced. On the
      contrary, ITB increased the production of interleukin (IL)-10 and the expression
      of heme oxygenase-1 (HO-1). ITB inhibited the production of catabolic mediators
      at concentrations able to increase IL-10 and HO-1 in OA cartilage, suggesting
      that this compound may be useful in the prevention of cartilage degradation.

PMID- 15242809
TI  - Prostaglandin H synthases: members of a class of quasi-linear threshold switches.
AB  - Prostaglandin H synthase (PTGS or COX) enzymes catalyze rate-limiting steps in
      the synthesis of potent prostanoids, including various prostaglandins,
      thromboxane, and prostacyclin. Mechanisms that have evolved for regulating
      prostanoid biosynthesis reflect a tension between achieving a rapid but measured
      response to cellular signals while minimizing spurious activation by signal
      noise. We found through mathematical modeling that the PTGS enzymes can be
      thought of as regulatory switches with approximately linear output above an
      adjustable threshold. In vivo synthesis allows continuous production while signal
      remains above threshold. Different isoforms show specific adaptions reflecting
      their physiological roles as constitutive or inducible enzymes. Mathematical
      modeling helps explain how these adaptations enable the PTGS1 and PTGS2 enzymes
      to maintain their physiological roles while avoiding potentially damaging
      consequences.

PMID- 15242810
TI  - Prevention of UVB-induced photoinflammation and photoaging by a polymethoxy
      flavonoid, nobiletin, in human keratinocytes in vivo and in vitro.
AB  - Exposure to ultraviolet B (UVB) irradiation induces acute skin inflammation such
      as erythema (sunburn) and edema, and prostaglandin (PG)E2 in the epidermis plays
      an important role as its prominent mediator. In the present study, we
      investigated the effect of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) from
      Citrus depressa, on the production of PGE2 in UVB-irradiated human keratinocytes.
      When keratinocytes were irradiated with 60mJ of UVB/cm2, the production and gene
      expression of cyclooxygenase (COX)-2, but not COX-1, were augmented along with an
      increase in PGE2 levels. The augmented COX-2 production was transcriptionally
      suppressed by nobiletin. In addition, neither the release of [14C]arachidonic
      acid from membrane phospholipids nor the gene expression of cytosolic
      phospholipase A2 (cPLA2) was altered in UVB-irradiated human keratinocytes.
      However, nobiletin was found to inhibit the release of [14C]arachidonic acid by
      decreasing the Ca2+ -dependent activity of cPLA2. Furthermore, topical treatment
      of nobiletin on the skin of the back prevented the UVB-induced increase of
      transepidermal water loss and hyperplasia of the epidermis in hairless mice.
      Therefore, these results suggest that nobiletin inhibits the UVB-induced
      production of PGE2 not only by suppressing the expression of COX-2 but also by
      decreasing the activity of cPLA2 in human keratinocytes. Furthermore, nobiletin
      may be useful as a novel sunscreen reagent to be applied for protection against
      photoinflammation and photoaging.

PMID- 15242811
TI  - Dendritic cells maturation promoted by M1 and M4, end products of steroidal
      ginseng saponins metabolized in digestive tracts, drive a potent Th1
      polarization.
AB  - Ginseng is a medicinal herb widely used in Asian countries, and many of its
      pharmacological actions are attributed to the ginsenosides. Dendritic cells (DCs)
      play a pivotal in the initiation of T-cell-mediated immune responses, making them
      an attractive cellular adjuvant for use in cancer vaccines. In this study, we
      investigated whether M1 and M4, end products of steroidal ginseng saponins
      metabolized in digestive tracts, can drive DCs maturation from human monocytes in
      vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days, followed by
      another 2 days in the presence of M1, M4 or TNF-alpha as a maturation stimulus.
      Stimulation with 20 microM of M1 or M4 increased expression level of CD80, CD83
      and CD86 as expressed by mean fluorescence intensity (MFI) and decreased
      endocytic activity. M4-primed mature DCs also displayed enhanced T cells
      stimulatory capacity in a MLR, as measured by T cell proliferation. Mature DCs
      differentiated with M1 or M4 induced the differentiation of naive T cells towards
      a helper T cell type 1 (Th1) response at DC/T (1:5) cells ratio depending on IL
      12 secretion. In CTL assay, the production of IFN-gamma and 51Cr release on M4
      primed mature DCs was more augmented than of immature DCs or TNF-alpha-primed
      mature DCs. These results suggest that M4 may be used on DC-based vaccines for
      cancer immunotherapy.

PMID- 15242812
TI  - Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid
      leukemia cell line-K562.
AB  - C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina
      platensis is of greater importance because of its various biological and
      pharmacological properties. It is a water soluble, non-toxic fluorescent protein
      pigment with potent anti-oxidant, anti-inflammatory and anti-cancer properties.
      In the present study the effect of highly purified C-PC was tested on growth and
      multiplication of human chronic myeloid leukemia cell line (K562). The results
      indicate significant decrease (49%) in the proliferation of K562 cells treated
      with 50 microM C-PC up to 48 h. Further studies involving fluorescence and
      electron microscope revealed characteristic apoptotic features like cell
      shrinkage, membrane blebbing and nuclear condensation. Agarose electrophoresis of
      genomic DNA of cells treated with C-PC showed fragmentation pattern typical for
      apoptotic cells. Flow cytometric analysis of cells treated with 25 and 50 microM
      C-PC for 48 h showed 14.11 and 20.93% cells in sub-G0/G1 phase, respectively. C
      PC treatment of K562 cells also resulted in release of cytochrome c into the
      cytosol and poly(ADP) ribose polymerase (PARP) cleavage. These studies also
      showed down regulation of anti-apoptotic Bcl-2 but without any changes in pro
      apoptotic Bax and thereby tilting the Bcl-2/Bax ratio towards apoptosis. These
      effects of C-PC appear to be mediated through entry of C-PC into the cytosol by
      an unknown mechanism. The present study thus demonstrates that C-PC induces
      apoptosis in K562 cells by cytochrome c release from mitochondria into the
      cytosol, PARP cleavage and down regulation of Bcl-2.

PMID- 15242813
TI  - Inhibitory effects of halothane on the thermogenic pathway in brown adipocytes:
      localization to adenylyl cyclase and mitochondrial fatty acid oxidation.
AB  - Volatile anesthetics such as halothane efficiently inhibit nonshivering
      thermogenesis as well as the cellular manifestation of that phenomenon:
      norepinephrine-induced respiration in brown adipocytes. To identify the molecular
      site(s) of action of such anesthetics, we have examined the effect of halothane
      on the sequential intracellular steps from the interaction of norepinephrine with
      isolated brown adipocytes to the stimulation of mitochondrial respiration
      (=thermogenesis). We did not identify an inhibition at the level of the
      adrenergic receptors, but a first site of inhibition was identified as the
      generation of cAMP by adenylyl cyclase; this led to inhibition of norepinephrine
      induced expression of the uncoupling protein-1 (UCP1) gene and reduced
      norepinephrine-induced lipolysis as secondary effects. Although an inhibition of
      lipolysis in itself would inhibit thermogenesis, circumvention of this inhibition
      revealed that a second, postlipolytic, site of inhibition existed: halothane also
      inhibited the stimulatory effect of exogenous fatty acids on cellular
      respiration. This inhibition was independent of the presence of UCP1 in the
      mitochondria of the cells and was thus not directly on the thermogenic uncoupling
      mechanism. Since not only fatty acid oxidation but also pyruvate oxidation were
      inhibited by halothane in isolated mitochondria, whereas glycerol-3-phosphate
      oxidation was not, the second site of action of halothane, evident when
      cyclase/lipolytic inhibition was circumvented, was located to the respiratory
      chain, complex I. The results thus explain the inhibition of nonshivering
      thermogenesis by identifying two sites of action of halothane in brown
      adipocytes. In addition, the results may open for new formulations of the
      molecular background to anesthesia.

PMID- 15242814
TI  - Activation and induction of cyclic AMP phosphodiesterase (PDE4) in rat pulmonary
      microvascular endothelial cells.
AB  - Regulation of the rolipram-sensitive cAMP-specific phosphodiesterase 4 (PDE4)
      gene family was studied in rat pulmonary microvascular endothelial cells
      (RPMVECs). Total PDE4 hydrolysis was increased within 10 min after addition of
      forskolin (10 microM), reached a maximum at 20-40 min, and then gradually
      declined in the cells. A similar activation of PDE4 activity was observed using a
      protein kinase A (PKA) activator, N(6)-monobutyryl cAMP. Both the forskolin and
      the N(6)-monobutyryl cAMP activated PDE4 activities were blocked by the PKA
      specific inhibitor, H89. This forskolin-stimulated and PKA-mediated short-term
      activation of PDE4 activity was further confirmed by in vitro phosphorylation of
      87kDa PDE4A6 and 83kDa PDE4B3 polypeptides using exogenous PKA Calpha. Increased
      immunoreactivity of phosphorylated PDE4A6 in situ was detected in Western blots
      by a PDE4A-phospho antibody specific to the putative PKA phosphorylation sites.
      Following long-term treatment of RPMVECs with rolipram and forskolin medium (RFM)
      for more than 60 days, PDE4 activity reached ten-fold higher values than control
      RPMVECS with twenty-fold increases detected in intracellular cAMP content. The
      RFM cells showed increased immunoreactivities of the constitutive 4A6 and 4B3
      isoforms plus two novel splice variants at 101kDa (4B1) and 71kDa (4B2).
      Treatment with H89 did not inhibit the PDE4 elevation in RFM cells. In addition
      to the increased levels of PDE4 in RFM cells, immunofluorescence showed a
      translocation of PDE4A and 4B to a nuclear region, which was normally not
      observed in RPMVECs. The PDE4 activity in RFM cells decayed rapidly with an even
      faster decline of intracellular cAMP content when forskolin/rolipram were removed
      from the medium. These results suggest that both the activation (short-term) and
      induction (long-term) of PDE4A/4B isoforms in RPMVECs are closely modulated by
      the intracellular cAMP content via both post-translational and synthetic
      mechanisms.

PMID- 15242815
TI  - Possible (enzymatic) routes and biological sites for metabolic reduction of
      BNP7787, a new protector against cisplatin-induced side-effects.
AB  - Disodium 2,2'-dithio-bis-ethane sulfonate (BNP7787) is under investigation as a
      potential new chemoprotector against cisplatin-induced nephrotoxicity. The
      selective protection of BNP7787 appears to arise from the preferential uptake of
      the drug in the kidneys, where BNP7787 would undergo intracellular conversion
      into mesna (2-mercapto ethane sulfonate), which in turn can prevent cisplatin
      induced toxicities. In the present study, we have investigated whether the
      reduction of BNP7787 into the reactive compound mesna is restricted to the kidney
      or whether it can also occur in other organs, cells and physiological
      compartments, including the cytosolic fraction of the renal cortex, plasma, red
      blood cells (RBCs), liver and small intestine from rats and several tumors (OVCAR
      3, MRI-H-207 and WARD). We also determined whether the endogenous thiols
      glutathione (GSH) and cysteine and the enzyme systems glutaredoxin and
      thioredoxin, which are all present in the kidney, can be involved in the BNP7787
      reduction. UV detection and micro-HPLC with dual electrochemical detection were
      used to analyze the various incubation mixtures. Our observations are that, in
      contrast to plasma, a very large reductive conversion of BNP7787 to mesna was
      measured in RBC lysate. Intact RBCs, however, did not take up BNP7787. Although
      BNP7787 could be reduced in cytosol of liver and several tumors, this reduction
      will not be relevant in vivo, since these tissues do not take up large amounts of
      BNP7787. Kidney cortex cytosol was, similar to the small intestine cytosol, able
      to substantially reduce BNP7787 to mesna. The ability to reduce BNP7787 in the
      presence of the endogenous thiols GSH and cysteine, the glutaredoxin system as
      well as the thioredoxin system, could at least in part explain the high BNP7787
      reductive activity of the kidney cortex cytosol. In conclusion, the high
      reduction of BNP7787 into mesna in the kidney as well as our earlier observation
      that the distribution of BNP7787 and mesna was mainly restricted to rat kidney
      are strong arguments in favor of selective protection of the kidney by BNP7787.

PMID- 15242816
TI  - Interactions of phospholipase D and cytochrome P450 protein stability.
AB  - Previous studies have suggested a relationship between cytochrome P450 (P450) 3A
      (CYP3A) conformation and the phospholipid composition of the associated membrane.
      In this study, we utilized a novel microsomal incubation system that mimics many
      of the characteristics of CYP3A degradation pathway that have been observed in
      vivo and in cultured cells to study the effects of phospholipid composition on
      protein stability. We found that addition of phosphatidylcholine-specific
      phospholipase D (PLD) stabilized CYP3A in this system, but that
      phosphatidylinositol-specific phospholipase C (PLC) was without effect. Addition
      of phosphatidic acid also stabilized CYP3A protein in the microsomes. The use of
      1,10-phenanthroline (phenanthroline), an inhibitor of PLD activity, decreased
      CYP3A stability in incubated microsomes. Similarly, 6-h treatment of primary
      cultures of rat hepatocytes with phenanthroline resulted in nearly complete loss
      of CYP3A protein. Treatment of rats with nicardipine or dimethylsulfoxide (DMSO),
      which have been shown to affect CYP3A stability, altered the phospholipid
      composition of hepatic microsomes. It did not appear, though, that the changes in
      phospholipid composition that resulted from these in vivo treatments accounted
      for the change in CYP3A stability observed in hepatic microsomes from these
      animals.

PMID- 15242817
TI  - Acetaminophen alters microsomal ryanodine Ca2+ channel in HepG2 cells
      overexpressing CYP2E1.
AB  - Acetaminophen hepatotoxicity is mediated by an initial metabolic activation and
      covalent binding of drug metabolites to liver proteins. Acetaminophen metabolites
      have been shown to affect rat liver microsomal Ca2+ stores, but the mechanism is
      not well understood. The aim of the current work was to find out if the
      metabolism of acetaminophen by CYP2E1 affects ryanodine-sensitive Ca2+ stores in
      the endoplasmic reticulum of transduced HepG2 cells. Five millimoles
      acetaminophen decreased proliferation of CYP2E1-overexpressing HepG2 cells,
      increased cytosolic Ca2+ levels and produced significant cytotoxicity, while only
      little, mostly anti-proliferative effects were found in HepG2 cells lacking
      CYP2E1. CYP2E1 inhibitor-4-methylpyrazole decreased drug cytotoxicity in
      transduced cells and normalized elevated Ca2+ levels. Acetaminophen cytotoxicity
      was significantly higher in CYP2E1 expressing cells with depleted glutathione. In
      the cells engineered to overexpress CYP2E1, an increased [3H]ryanodine affinity
      (by 45%) and increased ligand maximal binding to ryanodine receptors (by 64%) was
      observed, most probably due to increased association rate of [3H]ryanodine. Ca2+
      loading was decreased by about 53% in microsomal fractions isolated from
      transduced cells treated with acetaminophen and by 92% in glutathione depleted
      transfected cells treated with the drug. Ca2+/Mg2+-ATPase activity was unchanged
      in all microsomal fractions. Such effects were not observed in cells lacking
      CYP2E1. Our results confirm significant role of CYP2E1 in metabolic activation of
      acetaminophen and indicate that ryanodine receptors located in the liver
      endoplasmic reticulum are sensitive targets for acetaminophen metabolites.

PMID- 15242818
TI  - DNA damage and cytotoxicity in pancreatic beta-cells expressing human CYP2E1.
AB  - Epidemiological studies have identified nitrosamines as a risk factor for Type I
      (insulin dependent) diabetes mellitus. These compounds require bioactivation by
      cytochrome P450 2E1 (CYP2E1) for exertion of their toxic effects. Two mammalian
      insulin secreting pancreatic beta-cell lines BRIN BD11h2E1 and INS-1h2E1, which
      express human full length CYP2E1 cDNA, were used to elucidate the role of CYP2E1
      mediated nitrosamine bioactivation in pancreatic beta-cell dysfunction and
      destruction. These cell lines were shown to metabolise dimethylnitrosamine to
      produce formaldehyde at rates of 3.41 +/- 0.24 and 3.65 +/- 0.26 nmol/minmg
      microsomal protein, respectively. Following incubation with various
      concentrations of the nitrosamines dimethylnitrosamine, N-nitrosopyrrolidine and
      1-nitrospiperidine, all of which are bioactivated by CYP2E1, cytotoxicity and DNA
      damage were assessed using either the neutral red assay or comet assay
      respectively. Exposure of CYP2E1 expressing cells to nitrosamines resulted in
      significant dose-dependent decreases in cell viability, which were not seen in
      cells which did not express CYP2E1. Following culture with nitrosamine
      concentrations as low as 2.5mM 1-nitrosopiperidine, cell viability was
      significantly lower in BRIN BD11h2E1 and INS-1h2E1 cell lines in comparison to
      the BRIN BD11 and INS-1 parental cell lines (72.5 +/- 4.96 and 66.4 +/- 3.09% in
      BRIN BD11h2E1 and INS-1h2E1 versus 109.0 +/- 3.40 and 100.0 +/- 3.25% in BRIN
      BD11 and INS-1 respectively, P < 0.001). The highest dose of any of the
      nitrosamines tested failed to significantly reduce cell viability in the cells
      which lacked CYP2E1. Expression of CYP2E1 did not cause any change in the basal
      level of DNA damage in any of the cell lines. However, 16 h exposure to various
      nitrosamines resulted in significant dose-dependent DNA damage in the BRIN
      BD11h2E1 and INS-1h2E1 cells compared to their respective non CYP2E1-expressing
      parental controls, e.g. DNA damage increased from 34.38 +/- 1.25 to 44.01 +/-
      1.56% DNA in comet tail in BRIN BD11h2E1 cells incubated with 10 or 40 mM N
      nitrosopyrrolidine, respectively (P < 0.001). Similar treatment of the BRIN BD11
      and INS-1 cell lines did not result in a significant increase in DNA damage
      (20.33 +/- 1.0 and 22.4 +/- 0.98% DNA in comet tail). The pancreatic beta-cell is
      richly vascularised and expresses CYP2E1. This study suggests that expression of
      human CYP2E1 in pancreatic beta-cells make them highly susceptible to
      cytotoxicity and DNA damage by nitrosamines and other agents bioactivated by
      CYP2E1.

PMID- 15242819
TI  - Increased human cytomegalovirus replication in fibroblasts after treatment with
      therapeutical plasma concentrations of valproic acid.
AB  - Valproic acid (2-propylpentanoic acid, VPA), an effective inhibitor of histone
      deacetylases (HDAC) is used for the treatment of epilepsia. In this study,
      structure-activity relationships for the action of structurally modified VPA
      derivatives on human cytomegalovirus (HCMV) replication and HDAC inhibition were
      defined. Pretreatment of human foreskin fibroblasts with VPA (0.125-1mM) caused a
      concentration-dependent increase of HCMV immediate early and antigen late antigen
      expression. Structure-activity relationships of VPA derivatives for HCMV
      stimulation were compared to those for teratogenic action and those for HDAC
      inhibition. Side chain elongation and introduction of a triple bond in 4-position
      of the other chain caused teratogenicity, stimulated HCMV replication, and
      increased HDAC inhibition, as demonstrated by enhanced levels of acetylated
      histones. Teratogenic VPA derivatives with a branched chain in 3-position as well
      as a non-teratogenic anticonvulsive active VPA derivative did not stimulate HCMV
      or accumulation of acetylated histones. This demonstrates a strict correlation
      between inhibition of HDAC and increased HCMV replication.

PMID- 15242820
TI  - Reversal of antigen-dependent signaling by two mutations in antibody/receptor
      chimera: implication of inverse agonism in cytokine receptor superfamily.
AB  - Understanding the receptor activation mechanism is essential for the rational
      design of pharmacologically active ligand molecules. However, the activation
      mechanism of most cytokine receptors remains still unclear, and while agonism and
      antagonism have been described for ligand-mimetic peptides, there has been no
      report of inverse agonism that has been characterized for G protein-coupled
      receptors (GPCRs). To explore the activation mechanism of cytokine receptors,
      here we tried to investigate how agonism and antagonism could be altered by
      randomizing antibody variable region of an antibody/cytokine receptor chimera
      recognizing hen egg lysozyme (HEL) as an agonist. Based on our previous finding
      that the co-expression of V(H)-gp130 and V(L)-erythropoietin receptor (EpoR)
      chimeras transduced strict and efficient HEL-dependent cell growth signal, a V(H)
      gp130 library encoding four randomized CDR2 residues was retrovirally infected to
      IL-3-dependent Ba/F3 cells already transfected with V(L)-EpoR. The selection
      without IL-3 resulted in a clonal expansion of the transduced cells, and
      interestingly some of which showed HEL dose-dependent growth suppression. Our
      results clearly indicate that agonism and antagonism of the antibody/cytokine
      receptor chimera can be readily switched by a subtle modification of the ligand
      binding domain as well as that of GPCRs, also implying the existence of inverse
      agonism in cytokine receptor superfamily.

PMID- 15242821
TI  - Membrane-related effects underlying the biological activity of the anthraquinones
      emodin and barbaloin.
AB  - Commercial plant extracts containing anthraquinones are being increasingly used
      for cosmetics, food and pharmaceuticals due to their wide therapeutic and
      pharmacological properties. In this work, the interaction with model membranes of
      two representative 1,8-dihydroxyanthraquinones, barbaloin (Aloe) and emodin
      (Rheum, Polygonum), has been studied in order to explain their effects in
      biological membranes. Emodin showed a higher affinity for phospholipid membranes
      than barbaloin did, and was more effective in weakening hydrophobic interactions
      between hydrocarbon chains in phospholipid bilayers. Whereas emodin induced the
      formation of hexagonal-H(II) phase, barbaloin stabilized lamellar structures.
      Barbaloin promoted the formation of gel-fluid intermediate structures in
      phosphatidylglycerol membranes at physiological pH and ionic strength values. It
      is proposed that emodin's chromophore group is located at the upper half of the
      membrane, whereas barbaloin's one is in a deeper position but having its
      glucopyranosyl moiety near the phospholipid/water interface. Moreover, membrane
      disruption by emodin or barbaloin showed specificity for the two major
      phospholipids present in bacterial membranes, phosphatidylethanolamine and
      phosphatidylglycerol. In order to relate their strong effects on membranes to
      their biological activity, the capacity of these compounds to inhibit the
      infectivity of the viral haemorrhagic septicaemia rhabdovirus (VHSV), a negative
      RNA enveloped virus, or the growth of Escherichia coli was tested. Anthraquinone
      loaded liposomes showed a strong antimicrobial activity whereas these compounds
      in their free form did not. Both anthraquinones showed antiviral activity but
      only emodin was a virucidal agent. In conclusion, a molecular mechanism based on
      the effect of these compounds on the structure of biological membranes is
      proposed to account for their multiple biological activities. Anthraquinone
      loaded liposomes may suppose an alternative for antimicrobial, pharmaceutical or
      cosmetic applications.

PMID- 15242822
TI  - Inhibition of the functional expression of N-methyl-D-aspartate receptors in a
      stably transformed cell line by cyclosporin A.
AB  - The L(tk-) cell line L12-G10 stably transformed with the human N-methyl-D
      aspartate (NMDA) receptor subunits NR1-1a/NR2A showed a Ca(2+)-dependent increase
      in cell death, loss of mitochondrial membrane potential, and ATP depletion after
      agonist stimulation. Treatment of the cells with cyclosporine A (CsA) for 4h
      reduced glutamate-induced cell death by 60% (IC(50) of 7.1microM). The
      immunophilin binding drug FK506 was not effective. Short preincubation with CsA
      for 10 min already decreased the glutamate-induced loss of mitochondrial membrane
      potential while the NMDA receptor function is not affected. However, pretreatment
      of the cells with CsA (30 microM) for 6h reduced membrane associated NR1-1a
      protein amount by approximately 85%, whereas mRNA expression remained unaffected.
      These results suggest, that the cytoprotective effect of CsA in L12-G10 cells is
      due to the inhibition of the permeability transition pore on the one hand and to
      the inhibition of the expression of functional NMDA receptors by an additional
      posttranscriptional mechanism on the other hand.

PMID- 15242823
TI  - Signal transduction pathways implicated in the decrease in CYP1A1, 1A2 and 3A6
      activity produced by serum from rabbits and humans with an inflammatory reaction.
AB  - Incubation of serum from rabbits with a turpentine-induced inflammatory reaction
      and from humans with an upper respiratory viral infection with hepatocytes from
      rabbits with a turpentine-induced inflammatory reaction for 4h reduces total
      cytochrome P450 content and activity of cytochrome P450 isoforms CYP1A1/1A2 and
      3A6 without affecting the expression of these proteins. To document the signal
      transduction pathways implicated in the decrease in CYP1A1/1A2 and 3A6 activity,
      hepatocytes from rabbits with a turpentine-induced inflammatory reaction were
      incubated with serum from rabbits with a turpentine-induced inflammatory
      reaction, serum from individuals with a viral infection and interleukin-6 for 4h
      in presence of inhibitors of protein kinases. The sera-induced decrease in
      CYP1A1/1A2 and 3A6 activity was partially prevented by the inhibition of Janus
      associated protein tyrosine kinase, double-stranded RNA-dependent protein kinase,
      protein kinase C, and p42/44 mitogen-activated protein kinase. The serum from
      rabbits with a turpentine-induced inflammatory reaction increased the
      phosphorylation of Erk1/2, effect prevented by PD98059 but not by bis
      indolylmaleimide, a specific inhibitor of protein kinase C. The results
      demonstrated that the decrease in total cytochrome P450 content and in CYP1A1/1A2
      and 3A6 activity by sera and interleukin-6 involves the activation of protein
      tyrosine kinases, p42/44 mitogen-activated protein kinase and protein kinase C.
      Indirect evidence supported that nitric oxide is implicated in the decrease in
      activity of these enzymes.

PMID- 15242824
TI  - Methadone metabolism by human placenta.
AB  - Methadone pharmacotherapy is considered the standard for treatment of the
      pregnant heroin/opioid addict. One of the factors affecting the transfer kinetics
      of opioids across human placenta and their levels in the fetal circulation is
      their metabolism by the tissue. The aim of this investigation is to identify the
      enzyme(s) responsible for the metabolism of methadone, determine the kinetics of
      the reaction and the metabolites formed utilizing placental tissue obtained from
      term healthy pregnancies. Microsomal fractions of trophoblast tissue homogenates
      had the highest activity in catalyzing the metabolism of methadone. The product
      formed was identified by HPLC-UV as 2-ethylidine-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP). Inhibitors selective for cytochrome P450 (CYP)
      isozymes were used to identify the enzyme catalyzing the biotransformation of
      methadone. Aminoglutethimide and 4-hydroxyandrostenedione inhibited EDDP
      formation by 88 and 70%, respectively, suggesting that CYP19/aromatase is the
      enzyme catalyzing the reaction. This was confirmed by the effect of monoclonal
      antibodies raised against CYP19 that caused an 80% inhibition of the reaction.
      The apparent K(m) and V(max) values for the CYP19 catalyzed metabolism of
      methadone to EDDP were 424 +/- 92 microM and 420 +/- 89 pmol(mgprotein)(-1)min(
      1), respectively. Kinetic analysis of a cDNA-expressed CYP19 for the metabolism
      of methadone to EDDP was identical to that by placental microsomes. Taken
      together, these data indicate that CYP19/aromatase is the major enzyme
      responsible for the metabolism of methadone to EDDP in term human placentas
      obtained from healthy pregnancies.

PMID- 15242825
TI  - Protein intake regulates the vasodilatory function of the kidney and NMDA
      receptor expression.
AB  - Glycine infusion in normal rats causes an increase in renal plasma flow and
      glomerular filtration rate (GFR). Although the renal response to glycine infusion
      is well characterized, the mechanism initiating this vasodilation is unknown. We
      recently observed functionally active N-methyl-d-aspartate (NMDA) receptors in
      the kidney, located primarily in tubular structures. The mechanisms regulating
      activity of the NMDA receptor within the kidney are also unknown, as is its
      normal day-to-day functional role. Therefore, we hypothesize that dietary protein
      may impact the functional response to glycine infusion in both untreated rats and
      rats pretreated with angiotensin-converting enzyme (ACE) inhibitor and,
      furthermore, that renal NMDA receptors may be involved in the glycine response.
      Surprisingly, 2 wk of low-protein diet (8% protein vs. 21% protein in control
      diet) totally inhibited the glycine-induced vasodilation and GFR response.
      Associated with the absence of renal vasodilation, a significant reduction in
      proximal tubular reabsorption was observed during glycine infusion in low-protein
      diet rats. In contrast to the disease models previously studied in our
      laboratory, administration of ACE inhibitors did not restore the glycine response
      in rats treated with low-protein diet. Western blots of normal- and low-protein
      diet kidneys demonstrate that the newly described renal NMDA receptor is
      downregulated in rats fed a low-protein diet. Low-protein feeding results in loss
      of glycine-induced vasodilation and GFR responses associated with decreased renal
      NMDA receptor expression. Kidney NMDA receptor expression is conditioned by
      protein intake, and this receptor may play an important role in the kidney
      vasodilatory response to glycine infusion and protein feeding in rats.

PMID- 15242826
TI  - Increased release of serotonin from rat ileum due to dexfenfluramine.
AB  - Plasma levels of serotonin are elevated in primary pulmonary hypertension even
      after bilateral lung transplantation, suggesting a possible etiologic role.
      Serotonin is released primarily from the small intestine. Anorectic agents, such
      as dexfenfluramine, which can cause pulmonary hypertension, are known to inhibit
      potassium channels in vascular smooth muscle cells. We examined the hypothesis
      that dexfenfluramine may stimulate release of serotonin from the ileum by
      inhibition of K+ channels. In an isolated loop of rat ileum perfused with a
      physiological salt solution, the administration of dexfenfluramine, its major
      metabolite D-norfenfluramine, the potassium channel blocker 4-aminopyridine (5
      mM), and caffeine (30 mM) increased serotonin levels in the venous effluent.
      Potassium chloride (60 mM) tended to increase serotonin levels. In genetically
      susceptible individuals, dexfenfluramine may induce pulmonary hypertension by
      increasing cytosolic calcium in enterochromaffin cells of the small intestine,
      thus releasing serotonin and causing vasoconstriction. This work indicates that
      dexfenfluramine and its major metabolite d-norfenfluramine can increase serotonin
      release from the small intestine.

PMID- 15242827
TI  - Seasonality of dihydropyridine receptor binding in the heart of an anoxia
      tolerant vertebrate, the crucian carp (Carassius carassius L.).
AB  - Prolonged anoxia tolerance of facultative anaerobes is based on metabolic
      depression and thus on controlled reduction of energy-utilizing processes. One
      proposed survival mechanism is the closing of ion channels to decrease energetic
      cost of ion pumping (Hochachka PW. Science 231: 234-241, 1986). To test this
      hypothesis, the involvement of L-type Ca2+ channels in seasonal anoxia tolerance
      of the vertebrate heart was examined by determining the number of [methyl
      3H]PN200-110 (a ligand of L-type Ca2+ channel alpha-subunit) binding sites of the
      cardiac tissue and the density of Ca2+ current in ventricular myocytes of an
      anoxia-resistant fish species, the crucian carp. In their natural environment,
      the fish were exposed for > 3 mo of hypoxia (O2 < 2.5 mg/l) followed by almost 8
      wk of anoxia that resulted in abrupt depletion of cardiac glycogen stores in late
      spring. Unexpectedly, however, the number of [methyl-3H]PN200-110 binding sites
      did not decline in hypoxia/anoxia as predicted by the channel arrest hypothesis
      but remained constant for most of the year. However, in early summer, the number
      of [methyl-3H]PN200-110 binding sites doubled for a period of approximately 2 mo,
      which functionally appeared as a 74% larger Ca2+ current density. Thus the anoxia
      tolerance of the carp heart cannot be based on downregulation of Ca2+ channel
      units in myocytes but is likely to depend on suppressed heart rate, i.e.,
      regulation of the heart at the systemic level, and direct depressive effects of
      low temperature on Ca2+ current to achieve savings in cardiac work load and ion
      pumping. The summer peak in the number of functional Ca2+ channels indicates a
      short period of high cardiac activity possibly associated with reproduction and
      active perfusion of tissues after the winter stresses.

PMID- 15242828
TI  - Differential gene expression associated with euryhalinity in sea bream (Sparus
      sarba).
AB  - Certain fish have the remarkable capability of euryhalinity, being able to
      withstand large variations in salinity for indefinite periods. Using the highly
      euryhaline species, silver sea bream (Sparus sarba), as an experimental model,
      some of the molecular processes involved during ion regulation (Na+-K+-ATPase),
      cytoprotection [heat shock protein (hsp) 70], and growth (somatotropic axis) were
      studied. To perform these studies, seven key genes involved in these processes
      were cloned, and the tissue-specific expression profiles in fish adapted to
      salinities of 6 parts per thousand (ppt; hypoosmotic), 12 ppt (isoosmotic), 33
      ppt (seawater), and 50 ppt (hypersaline) were studied. In gills, the
      transcriptional and translational expression profiles of Na+-K+-ATPase alpha- and
      beta-subunit genes were lowest in isoosmotic-adapted fish, whereas in kidneys the
      expression of the beta-subunit increased in seawater- and hypersaline-adapted
      groups. The hsp70 multigene family, comprising genes coding for heat shock
      cognate (hsc70), inducible heat shock protein (hsp70), and a heat shock
      transcription factor (hsf1), was found to be highly upregulated in gills of
      seawater- and hypersaline-adapted fish. In liver, hsc70 expression was lowest in
      isoosmotic groups, and in kidneys the hsp70 multigene family remained unchanged
      over the salinity range tested. The regulation of the somatotropic axis was
      studied by measuring pituitary growth hormone expression and liver IGF-I
      expression in salinity-adapted fish. The expression amounts of both genes
      involved in the somatotropic axis were highest in fish maintained at an
      isoosmotic salinity. The results of this study provide new information on key
      molecular processes involved in euryhalinity of fish.

PMID- 15242829
TI  - Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric
      emptying in rats.
AB  - We compared the effects of the two molecular forms of the brain-gut peptide YY
      (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received
      20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol x
      kg(-1) x min(-1)) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol x kg(
      1) x min(-1)), either alone or combined, and gastric emptying of saline was
      measured during the last 10 min of infusion. For comparison, human PYY(3-36) was
      administered at 0, 17, and 50 pmol x kg(-1) x min(-1). Gastric emptying was
      decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol x kg(-1)
      x min(-1) of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50,
      100, and 170 pmol x kg(-1) x min(-1) of rat PYY(3-36); and by 35 and 53% in
      response to 17 and 50 pmol x kg(-1) x min(-1) of human PYY(3-36), respectively.
      Estimated ED50s were 470 and 37 pmol x kg(-1) x min(-1) for rat PYY(1-36) and
      PYY(3-36), respectively. In general, within an experiment, coadministration of
      PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was
      comparable to that produced when either peptide was given alone. We conclude that
      1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent
      inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude
      more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and
      rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36)
      do not appear to interact in an additive or synergistic manner to inhibit gastric
      emptying.

PMID- 15242830
TI  - Reduced baroreflex control of heart period after bed rest is normalized by acute
      plasma volume restoration.
AB  - Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an
      apparent abnormality of baroreflex regulation of cardiac period. In a previous
      study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute
      induced hypovolemia led to similar impairments in spontaneous baroreflex control
      of cardiac period, suggesting that a reduction in plasma volume may be
      responsible for this abnormality after bed rest. Therefore we hypothesized that
      this reduced "baroreflex function" could be restored by intravenous volume
      infusion equivalent to the reduction in plasma volume after bed rest. Six healthy
      subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial
      blood pressure and ECG were recorded during 6 min of spontaneous respiration and
      fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic
      blood pressure and R-R interval was performed. Plasma volume was measured with
      Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz
      catheter). After bed rest, studies were repeated before and after plasma volume
      restoration, with which both plasma volume and left ventricular end-diastolic
      pressure were restored to pre-bed rest levels by intravenous dextran40 infusion
      (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an
      index of vagally mediated arterial-cardiac baroreflex function, decreased
      significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest.
      However, reduced transfer function gain was normalized to the pre-bed rest level
      (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result
      confirms that reductions in plasma volume, rather than a unique autonomic nervous
      system adaptation to bed rest, are largely responsible for the observed changes
      in spontaneous arterial-cardiac baroreflex function after bed rest.

PMID- 15242831
TI  - Endogenous testosterone increases L-type Ca2+ channel expression in porcine
      coronary smooth muscle.
AB  - Evidence indicates that gender and sex hormonal status influence cardiovascular
      physiology and pathophysiology. We recently demonstrated increased L-type voltage
      gated Ca2+ current (ICa,L) in coronary arterial smooth muscle (CASM) of male
      compared with female swine. The promoter region of the L-type voltage-gated Ca2+
      channel (VGCC) (Cav1.2) gene contains a hormone response element that is
      activated by testosterone. Thus the purpose of the present study was to determine
      whether endogenous testosterone regulates CASM ICa,L through regulation of VGCC
      expression and activity. Sexually mature male and female Yucatan swine (7-8 mo;
      35-45 kg) were obtained from the breeder. Males were left intact (IM, n=8),
      castrated (CM, n=8), or castrated with testosterone replacement (CMT, n=8; 10
      mg/day Androgel). Females remained gonad intact (n=8). In right coronary
      arteries, both Cav1.2 mRNA and protein were greater in IM compared with intact
      females. Cav1.2 mRNA and protein were reduced in CM compared with IM and restored
      in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM
      compared with IM and restored in CMT. In males, a linear relationship was found
      between serum testosterone levels and ICa. In vitro, both testosterone and the
      nonaromatizable androgen, dihydrotestosterone, increased Cav1.2 expression.
      Furthermore, this effect was blocked by the androgen receptor antagonist
      cyproterone. We conclude that endogenous testosterone is a primary regulator of
      Cav1.2 expression and activity in coronary arteries of males.

PMID- 15242832
TI  - Nitric oxide donor induces temporal and dose-dependent reduction of gene
      expression in human endothelial cells.
AB  - The present study tested the hypothesis that acute increases in nitric oxide (NO)
      exert substantial influences on gene transcription in endothelial cells (ECs) via
      guanylyl cyclase (GC). Human umbilical veins ECs (HUVECs) were exposed to 0.1, 1,
      and 10 mM of sodium nitroprusside (SNP) for 4 h and to 1 mM SNP or 250 microM of
      (Z)-1[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA
      NONOate) for 2, 4, 8, and 24 h. Also, cells were exposed to DETA-NONOate in the
      presence and absence of the GC inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1
      one (ODQ; 10 microM) for 4 h. RNA was isolated, reverse transcribed, Cy3 and Cy5
      labeled, and analyzed using cDNA microarrays. Increasing doses of SNP
      predominantly depressed gene expression in HUVECs. Gene function was related to
      growth, adhesion, and cell structure. DETA-NONOate evoked a wave of expression
      changes (maximum at 4 h), with a remarkable downregulation of the transcription
      factors MSX1, RELB, and Egr-1. Both SNP- and DETA-NONOate-induced gene expression
      had faded after 24 h, despite continued elevation of cGMP in the medium.
      Coadministration of ODQ decreased many, but not all, of the transcriptional
      responses to DETA-NONOate. NO pronouncedly depressed EC gene expression, in
      particular of transcription factors. The observation that many, but not all,
      transcriptional changes induced by NO could be inhibited by inhibition of GC
      indicates the presence of GC-independent NO actions on gene expression. Thus EC
      gene expression responds to NO; however, the transcriptional response fades
      during prolonged exposure. This could allow the EC to respond to increased shear,
      without vigorous changes in gene expression.

PMID- 15242833
TI  - Time-dependent remodeling of transmural architecture underlying abnormal
      ventricular geometry in chronic volume overload heart failure.
AB  - To test the hypothesis that the abnormal ventricular geometry in failing hearts
      may be accounted for by regionally selective remodeling of myocardial laminae or
      sheets, we investigated remodeling of the transmural architecture in chronic
      volume overload induced by an aortocaval shunt. We determined three-dimensional
      finite deformation at apical and basal sites in left ventricular anterior wall of
      six dogs with the use of biplane cineradiography of implanted markers. Myocardial
      strains at end diastole were measured at a failing state referred to control to
      describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk
      (means +/- SE) of volume overload, the myocardial volume within the marker sets
      increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/-
      0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet
      shear at the basal site increased progressively toward the final study (0.040 +/-
      0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a
      significant increase in wall thickness at the final study (0.181 +/- 0.047; P <
      0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of
      the transmural architecture is regionally heterogeneous in chronic volume
      overload. The early differences in fiber elongation seem most likely due to a
      regional gradient in diastolic wall stress, whereas the late differences in wall
      thickness are most likely related to regional differences in the laminar
      architecture of the wall. These results suggest that the temporal progression of
      ventricular remodeling may be anatomically designed at the level of regional
      laminar architecture.

PMID- 15242834
TI  - Opening of mitochondrial KATP channels enhances cardioprotection through the
      modulation of mitochondrial matrix volume, calcium accumulation, and respiration.
AB  - Previously, we have shown that the pharmacological opening of the mitochondrial
      ATP-sensitive K channels with diazoxide (DZX) enhances the cardioprotection
      afforded by magnesium-supplemented potassium (K/Mg) cardioplegia. To determine
      the mechanisms involved in the cardioprotection afforded by K/Mg + DZX
      cardioplegia, rabbit hearts (n=24) were subjected to isolated Langendorff
      perfusion. Control hearts were perfused for 75 min. Global ischemia (GI) hearts
      were subjected to 30 min of equilibrium, 30 min of GI, and 15 min of reperfusion.
      K/Mg and K/Mg + DZX cardioplegia hearts received either K/Mg or K/Mg + DZX for 5
      min before GI and reperfusion. Tissue was harvested for mitochondrial isolation
      and transmission electron microscopy (TEM). Mitochondrial structure, area, matrix
      volume, free calcium, and oxygen consumption were determined. TEM demonstrated
      that GI mitochondria were damaged and that K/Mg and K/Mg + DZX preserved
      mitochondrial structure. TEM and light scattering demonstrated separately that
      mitochondrial matrix and cristae area and matrix volume were significantly
      increased after GI and reperfusion with GI > K/Mg + DZX > K/Mg hearts (P <0.05
      vs. control). Mitochondrial free calcium was significantly increased in GI and
      K/Mg hearts. K/Mg + DZX significantly decreased mitochondrial free calcium
      accumulation (P <0.05 vs. GI and K/Mg). State 3 oxygen consumption and
      respiratory control index in malate (complex I substrate)- and succinate (complex
      II substrate)-energized mitochondria were significantly decreased (P <0.05 vs.
      control) in the GI and K/Mg + DZX groups. These data indicate that the enhanced
      cardioprotection afforded by K/Mg + DZX cardioplegia occurs through the
      preservation of mitochondrial structure and the significant decrease in
      mitochondrial free calcium accumulation and mitochondrial state 3 oxygen
      consumption.

PMID- 15242835
TI  - Adenylyl cyclase type VI corrects cardiac sarcoplasmic reticulum calcium uptake
      defects in cardiomyopathy.
AB  - Calcium malfunction plays a central role in heart failure. Here, we provide
      evidence that adenylyl cyclase type VI restores sarco(endo)plasmic reticulum 2a
      (SERCA2a) affinity for calcium and maximum velocity of cardiac calcium uptake by
      sarcoplasmic reticulum in murine dilated cardiomyopathy. Restoration of normal
      SERCA2a affinity for calcium is associated not only with decreased phospholamban
      protein expression but also with increased phospholamban phosphorylation by PKA
      activation. The ratio of phosphorylated ryanodine receptor 2 (RyR2) to RyR2
      protein was increased, but the amount of phosphorylated RyR2 was unaffected.
      These data provide a possible mechanism by which adenylyl cyclase type VI (in
      contrast to other signaling elements associated with increased cAMP generation)
      has a salutary effect in the failing heart.

PMID- 15242836
TI  - Periods of intermittent hypoxic apnea can alter chemoreflex control of
      sympathetic nerve activity in humans.
AB  - Obstructive sleep apnea is associated with sustained elevation of muscle
      sympathetic nerve activity (MSNA) and altered chemoreflex control of MSNA, both
      of which likely play an important role in the development of hypertension in
      these patients. Additionally, short-term exposure to intermittent hypoxic apneas
      can produce a sustained elevation of MSNA. Therefore, we tested the hypothesis
      that 20 min of intermittent hypoxic apneas can alter chemoreflex control of MSNA.
      Twenty-one subjects were randomly assigned to one of three groups (hypoxic apnea,
      hypercapnic hypoxia, and isocapnic hypoxia). Subjects were exposed to 30 s of the
      perturbation every minute for 20 min. Chemoreflex control of MSNA was assessed
      during baseline, 1 min posttreatment, and every 15 min throughout 180 min of
      recovery by the MSNA response to a single hypoxic apnea. Recovery hypoxic apneas
      were matched to a baseline hypoxic apnea with a similar nadir oxygen saturation.
      A significant main effect for chemoreflex control of MSNA was observed after 20
      min of intermittent hypoxic apneas (P <0.001). The MSNA response to a single
      hypoxic apnea was attenuated 1 min postexposure compared with baseline (P
      <0.001), became augmented within 30 min of recovery, and remained augmented
      through 165 min of recovery (P <0.05). Comparison of treatment groups revealed no
      differences in the chemoreflex control of MSNA during recovery (P=0.69). These
      data support the hypothesis that 20 min of intermittent hypoxic apneas can alter
      chemoreflex control of MSNA. Furthermore, this response appears to be mediated by
      hypoxia.

PMID- 15242837
TI  - Saturation of high-frequency oscillations of R-R intervals in healthy subjects
      and patients after acute myocardial infarction during ambulatory conditions.
AB  - This study was designed to assess the relationship between R-R interval length
      and heart rate (HR) variability in healthy subjects and patients after an acute
      myocardial infarction (AMI). Twenty-four-hour ambulatory ECG recordings were
      obtained for 76 healthy subjects and 82 post-AMI patients. The high-frequency
      (HF, 0.15-0.4 Hz) spectral power of R-R intervals was analyzed in 5-min sequences
      over 24 h and plotted as a function of the corresponding mean R-R interval
      length. Quadratic regression model was used to study the relationship between R-R
      interval length and HF power. If a distinct deflection point (R-R0) occurred in
      the quadratic regression (r >0.50) model before maximum R-R interval, indicating
      the plateau of HF power, the relationship between R-R interval and HF power was
      defined as saturated. Otherwise, the relationship was defined as linear (r >0.50)
      or low correlated (r >0.50). The relationship was saturated in 35, linear in 38,
      and low correlated in 3 healthy subjects. In post-AMI patients, the relationship
      was saturated in 9 subjects, linear in 44 subjects, and low correlated in 29
      patients. The HF power analyzed from the 24-h period did not differ between the
      saturated and linear groups, but when analyzed from the linear portion only, HF
      spectral power was smaller in the linear than the saturated group both among
      healthy subjects (P <0.05) and post-AMI patients (P <0.05). Saturation of the HF
      oscillations of R-R intervals is a common phenomenon in healthy subjects and also
      present in post-AMI patients during ambulatory conditions. This saturation effect
      may bias the quantification of cardiac vagal function when HR variability is
      analyzed from Holter recordings.

PMID- 15242838
TI  - Novel method for measuring junctional proton permeation in isolated ventricular
      myocyte cell pairs.
AB  - Partial exposure of single ventricular myocytes to membrane-permeant weak acids
      or bases, using a dual-microperfusion technique, generates large and stable
      intracellular pH (pHi) gradients. In this study, we have investigated the
      feasibility of using the technique to estimate junctional proton permeability.
      This was done by recording the pHi gradient developed across the junctional
      region of a pair of conjoined ventricular myocytes, isolated enzymically from a
      guinea pig heart when one of the cells was partially exposed to acetate or
      ammonium. We show that under HEPES-buffered conditions, the junctional
      discontinuity in the pHi profile can be used to derive an apparent proton
      permeability coefficient (PHapp). The mean PHapp obtained was 4.45 +/- 0.21.10(
      4) cm/s (n=43) at an average junctional pHi of 7.04 +/- 0.02. In the presence of
      the junctional inhibitor alpha-glycyrrhetinic acid, exposure of the proximal cell
      to weak acid or base produced no pHi change in the distal cell, confirming that
      distal changes were normally caused by acid-base flux through connexons assembled
      into junctional channels. The validity of the dual-microperfusion method was
      tested further by using a diffusion-permeation-reaction model for intracellular
      protons, designed to highlight possible errors in the estimates of PHapp. Our
      technique for measuring PHapp provides a useful alternative to the previous, more
      invasive technique of locally loading acid through a cell-attached patch pipette.
      The technique may provide a simple method for investigating the factors
      regulating cell-to-cell proton transmission.

PMID- 15242839
TI  - Novel targets of ANG II regulation in mouse heart identified by serial analysis
      of gene expression.
AB  - Although the central role of ANG II in cardiovascular homeostasis is well
      appreciated, the molecular circuitry of its many actions is not completely
      understood. With the use of serial analysis of gene expression to assess global
      transcriptional changes in the heart of mice after continuous 7-day ANG II
      administration, we identified patterns of gene expression indicative of cardiac
      remodeling, including coordinate regulation of genes previously described in a
      context of processes associated with hypertrophy and fibrosis. In addition, we
      discovered several novel ANG II targets, including characterized genes of known
      function, recently annotated genes of unknown function, and the putative genes
      not yet present in current databases. The serial analysis of gene expression
      approach to assess the role of ANG II presented in this report provides new
      venues for inquiries into ANG II-mediated cardiac function.

PMID- 15242840
TI  - Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator
      associated pneumonia.
AB  - The impact of methicillin resistance on morbidity and mortality of patients
      suffering from severe Staphylococcus aureus infections remains highly
      controversial. We analyzed a retrospective cohort of 97 patients with methicillin
      susceptible and 74 patients with methicillin-resistant Staphylococcus aureus
      ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was
      appropriate for every patient. Patients with methicillin-resistant Staphylococcus
      aureus VAP were older, had higher disease-severity scores, and had been on
      mechanical ventilation longer at onset of VAP. Factors associated with 28-day
      mortality retained by multivariate logistic regression analysis were: age (odds
      ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1
      organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p =
      0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22).
      The percentages of infection relapse or superinfection did not differ
      significantly between the two patient groups. In conclusion, after controlling
      for clinical and physiologic heterogeneity between groups, methicillin resistance
      did not significantly affect 28-day mortality of patients with Staphylococcus
      aureus VAP receiving appropriate antibiotics.

PMID- 15242841
TI  - Is interleukin-13 critical in maintaining airway hyperresponsiveness in allergen
      challenged mice?
AB  - Interleukin (IL)-13 is regarded as being a central effector in the
      pathophysiology of airway hyperresponsiveness. We have described a mouse model in
      which chronic allergen exposure results in sustained airway hyperresponsiveness
      and aspects of airway remodeling, and here sought to demonstrate that this
      component of airway hyperresponsiveness is independent of biologically active IL
      13. Sensitized mice were subjected to either brief or chronic periods of allergen
      exposure and studied 24 hours after brief or 4 weeks after chronic allergen
      inhalation. A soluble murine anti-IL-13 receptor fusion protein that specifically
      binds to and neutralizes IL-13 was given daily during the 4 days before the day
      of outcome measurements in both protocols. Outcome measurements included airway
      responses to intravenous methacholine, bronchoalveolar lavage fluid cell counts,
      and airway morphometry. Compared with the saline control, brief allergen
      challenge resulted in airway hyperresponsiveness, which was prevented by anti-IL
      13 treatment. Chronic allergen challenge resulted in sustained airway
      hyperresponsiveness and indices of airway remodeling; IL-13 blockade failed to
      reverse this sustained airway hyperresponsiveness. These results confirm that IL
      13 is critical for the development of airway hyperresponsiveness associated with
      brief allergen exposure, but is not necessary to maintain the sustained airway
      hyperresponsiveness associated with airway remodeling.

PMID- 15242842
TI  - Quantitative assessment of tracheal collapsibility in infants with
      tracheomalacia.
AB  - Infantile tracheomalacia is a potentially life-threatening disease requiring
      prolonged artificial respiratory support. Diagnosis and management of this
      disease may be further improved by establishing a suitable objective and
      quantitative assessment protocol for tracheal collapsibility. It is our
      hypothesis that tracheal collapsibility can be represented by the relationship
      between intraluminal pressure and the cross-sectional area of the trachea. To
      test this hypothesis, static pressure/area relationships of the trachea were
      obtained from anesthetized and paralyzed infants, who were diagnosed as having
      tracheomalacia by endoscopic observation. These relationships were fitted on a
      linear regression model, followed by calculation of the estimated closing
      pressure. The tracheal closing pressure ranged from -8 to -27 cm H(2)O,
      suggesting easy collapsibility of the trachea during crying or coughing and
      noncollapsibility during the spontaneous respiratory cycle, which coincided with
      the infants' symptoms. It is our conclusion that tracheal collapsibility of
      infants with tracheomalacia can be quantitatively assessed by the static
      pressure/area relationship of the trachea obtained under general anesthesia and
      paralysis.

PMID- 15242843
TI  - The influence of active and passive smoking on habitual snoring.
AB  - The impact of active smoking, passive smoking, and obesity on habitual snoring in
      the population is mainly unknown. We aimed to study the relationship of habitual
      snoring with active and passive tobacco smoking in a population-based sample. A
      total of 15,555 of 21,802 (71%) randomly selected men and women aged 25-54 years
      from Iceland, Estonia, Denmark, Norway, and Sweden answered a postal
      questionnaire. Habitual snoring, defined as loud and disturbing snoring at least
      3 nights a week, was more prevalent among current smokers (24.0%, p < 0.0001) and
      ex-smokers (20.3%, p < 0.0001) than in never-smokers (13.7%). Snoring was also
      more prevalent in never-smokers exposed to passive smoking at home on a daily
      basis than in never-smokers without this exposure (19.8% vs. 13.3%, p < 0.0001).
      The frequency of habitual snoring increased with the amount of tobacco smoked.
      Active smoking and passive smoking were related to snoring, independent of
      obesity, sex, center, and age. Ever smoking accounted for 17.1% of the
      attributable risk of habitual snoring, obesity (body mass index > or = 30
      kg/m(2)) for 4.3%, and passive smoking for 2.2%. Smoking, both current and ex
      smoking, is a major contributor to habitual snoring in the general population.
      Passive smoking is a previously unrecognized risk factor for snoring among
      adults.

PMID- 15242844
TI  - Contributions of non-occupational activities to total noise exposure of
      construction workers.
AB  - This paper describes how exposures received during routine and episodic non
      occupational activities contribute to total noise exposure in a group of
      occupationally exposed workers. Two-hundred and sixty-six construction
      apprentices enrolled in a longitudinal hearing loss study and completed
      questionnaires at 1 yr of follow-up to determine their episodic activities (e.g.
      concert attendance, power tool use, firearms exposure). Noise exposure levels for
      these episodic exposures were determined from the published literature. Routine
      activities were assessed using activity cards filled out over 530 subject-days,
      along with noise dosimetry measurements made over 124 subject-days of
      measurement. Equivalent Leq exposure levels were then calculated for specific
      activities. These activity-specific Leq values were combined into estimated
      individual annual Leq exposure levels for the 6760 nominal annual non
      occupational hours in a year (LAeq6760h), which were then transformed into
      equivalent levels for a 2000 h exposure period (LA2000hn) for comparison with
      occupational noise exposure risk criteria. The mean non-occupational LAeq6760h
      exposure values for the cohort ranged from 56 to 87 dBA (equivalent LA2000hn 62
      93 dBA). At the mid range of the routine and episodic activity exposure level
      distribution, the mean LAeq6760h was 73 dBA (LA2000hn 78 dBA). Nineteen percent
      of the LA2000hn non-occupational exposures exceeded 85 dBA, the generally
      recommended occupational limit for a 2000 h workyear, at the mid-range of
      exposure levels. Due to a lack of available data, firearms use could not be
      incorporated into the total noise exposure estimates. However, firearms users
      reported more exposure to other noisy non-occupational activities and had
      statistically significantly higher estimated exposure levels even without
      including their firearms exposure than did non-shooters. When compared with the
      high levels of occupational noise found in construction, non-occupational noise
      exposures generally present little additional exposure for most workers. However,
      they may contribute significantly to overall exposure in the subset of workers
      who frequently participate in selected noisy activities.

PMID- 15242845
TI  - Characterization of ciliated bronchial epithelium 1, a ciliated cell-associated
      gene induced during mucociliary differentiation.
AB  - Lung epithelial structure is altered in asthma; however, the precise mechanisms
      underlying epithelial repair, including differentiation from basal to columnar
      epithelial cells, are not well defined. In the course of random sequencing of a
      cDNA library from human lung biopsies, we have identified a novel gene, ciliated
      bronchial epithelium 1 (CBE1). Expression of CBE1 was induced during in vitro
      differentiation of bronchial epithelial cells. Synchronous expression with tektin
      and hepatocyte nuclear factor 3/forkhead homologue 4, down-regulation by
      interleukin-13, and its tissue distribution strongly suggested that CBE1 is
      associated with ciliated cells. Two isoforms of the 0.7-kb full-length cDNA were
      identified, resulting in open reading frames with different carboxyl termini,
      with no homology to known proteins. Expression of CBE1 in ciliated epithelial
      cells was confirmed by immunohistochemistry. Quantitative reverse transcription
      polymerase chain reaction analysis using bronchial biopsies showed no difference
      of expression of CBE1 between normal subjects and subjects with asthma.
      Expression studies showed that CBE1 is nuclear- or perinuclear-localized,
      depending on cell type. Regulated expression during differentiation and the
      subcellular localization of CBE1 suggest that it may play an important role in
      the differentiation and/or function of ciliated cells in human airways.

PMID- 15242846
TI  - Cigarette smoke induces persisting increases of vasoactive mediators in pulmonary
      arteries.
AB  - The pathogenesis of cigarette smoke-induced pulmonary hypertension is not
      understood. We previously reported that a single smoke exposure acutely but
      transiently upregulated gene expression of the vasoconstrictor/vasoproliferative
      agents endothelin (ET) and vascular endothelial growth factor in pulmonary
      arteries from rat lungs. To determine whether similar changes occurred with
      chronic smoke exposure, we exposed Hartley guinea pigs, an outbred strain that
      develops pulmonary hypertension, to smoke for 2, 4, or 12 wk. Small
      intrapulmonary artery branches were isolated using laser capture microdissection,
      and gene expression was determined by real-time polymerase chain reaction. In
      smoke-exposed animals, there were significantly elevated but variable increases
      in gene expression, with some animals demonstrating 30- to 50-fold increases.
      Increases in ET and vascular endothelial growth factor expression occurred early
      and persisted through the exposure period, whereas increases in expression of the
      vasodilator, endothelial nitric oxide synthase, developed more slowly. Protein
      levels of these mediators were also elevated by immunohistochemical staining and
      correlated with increases in gene expression levels. We conclude that, in some
      animals, cigarette smoke induces persisting and marked vascular production of
      mediators that control vascular muscularization and contraction/dilation. These
      changes may be important in the development of smoke-induced pulmonary
      hypertension.

PMID- 15242847
TI  - Corticosteroid and cytokines synergistically enhance toll-like receptor 2
      expression in respiratory epithelial cells.
AB  - Respiratory epithelial cells play important roles not only in host defense
      mechanisms, but also in inflammatory responses. Inhaled corticosteroids are
      widely used for the treatment of patients with inflammatory lung disorders,
      including asthma, chronic obstructive pulmonary disease, and sarcoidosis.
      Corticosteroids effectively reduce the production of inflammatory mediators, such
      as cytokines and chemokines. Although these molecules are also essential for host
      defense responses, there is no convincing evidence that inhaled corticosteroids
      increase susceptibility to lower respiratory tract infections. To test the
      involvement of Toll-like receptor (TLR) family molecules in this phenomenon, we
      examined the effects of various cytokines and corticosteroid on the expression of
      TLRs in human respiratory epithelial cells. Among the TLRs tested, TLR2
      expression was significantly enhanced after stimulation with a combination of
      tumor necrosis factor-alpha and interferon-gamma. Dexamethasone synergistically
      enhanced TLR2 expression in combination with tumor necrosis factor-alpha and
      interferon-gamma in terms of both mRNA and protein levels. Furthermore, increased
      cell-surface TLR2 was functional, judging from the remarkable induction of
      interleukin-6, interleukin-8, and beta-defensin-2 after stimulation with
      peptidoglycan. These results provide evidence for a novel function of
      corticosteroids in airway inflammatory disorders, and indicate that the use of
      inhaled corticosteroids in such disorders may have a beneficial role in host
      defense mechanisms.

PMID- 15242848
TI  - Hyperventilation.

PMID- 15242849
TI  - Flies, mice, and surprises in dissecting environmental lung injury.

PMID- 15242850
TI  - Interferon-gamma 1b in idiopathic pulmonary fibrosis: what we know and what must
      we learn.

PMID- 15242851
TI  - A century of pulmonary hemodynamics.

PMID- 15242852
TI  - Mentoring: seven roles and some specifics.

PMID- 15242853
TI  - Diagnostic access for sleep apnea in Spain.

PMID- 15242854
TI  - Diagnostic access for sleep apnea in Hong Kong.

PMID- 15242855
TI  - Endothelial dysfunction and sleep apnea.

PMID- 15242856
TI  - Ethics and standard of care in clinical trials.

PMID- 15242857
TI  - Nicotine and hypersensitivity pneumonitis.

PMID- 15242858
TI  - Reduced vascular NO bioavailability in diabetes increases platelet activation in
      vivo.
AB  - OBJECTIVE: Platelet activation is a feature of cardiovascular disease that is
      also characterized by endothelial dysfunction. The direct relationship between
      impaired endothelium-derived NO bioavailability and platelet activation remains
      unclear. We investigated whether acute inhibition of NO production modulates
      platelet activation in mice and whether specific rescue of endothelial function
      in diabetes modifies platelet activation. METHODS AND RESULTS: Intravenous
      injection of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester in wild
      type (WT) mice significantly reduced platelet vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation and increased platelet surface expression
      of P-selectin, CD40 ligand, and fibrinogen platelet binding, demonstrating that
      NO production exerts tonic inhibition of platelet activation in mice. Diabetes
      was induced by streptozotocin injection in WT or endothelial-targeted guanosine
      5'-triphosphate cyclohydrolase I (GCH)-transgenic (GCH-Tg) mice protected from
      endothelial dysfunction in diabetes by sustained levels of tetrahydrobiopterin in
      vascular endothelium. Platelet VASP phosphorylation was significantly reduced in
      diabetic WT but not in diabetic GCH-Tg mice. P-selectin, CD40 ligand expression,
      and fibrinogen binding were increased in diabetic WT mice but remained unchanged
      compared with controls in endothelial-targeted GCH-Tg mice. CONCLUSIONS: Platelet
      activation results from acute and chronic reduction in NO bioactivity. Rescue of
      platelet activation in diabetes by endothelial-specific restoration of NO
      production demonstrates that platelet function in vivo is principally regulated
      by endothelium-derived NO. Endothelial dysfunction caused by uncoupling of
      endothelial NO synthase is well described in diabetes mellitus and may lead to
      platelet activation. Acute loss of systemic NO bioavailability causes platelet
      activation. eNOS uncoupling prevention in diabetes preserved systemic NO
      bioavailability and maintained a physiological platelet state without activation
      in vivo.

PMID- 15242859
TI  - Acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) is responsible for
      elevated intestinal ACAT activity in diabetic rats.
AB  - OBJECTIVE: Diabetes-induced dyslipidemia is seen in streptozotocin-induced
      diabetic rats. This is caused, in part, by elevated intestinal acyl-coenzyme
      A:cholesterol acyltransferase (ACAT) activity. Because two ACAT isozymes (ACAT-1
      and ACAT-2) were identified, in the present study we determined which ACAT
      isozyme was involved in the elevated intestinal ACAT activity in diabetic rats.
      METHODS AND RESULTS: We cloned a full-length cDNA of rat ACAT-2. Its
      overexpression in ACAT-deficient AC29 cells demonstrated that the ACAT activity
      is derived from the cloned cDNA, and a 45-kDa protein of rat ACAT-2 cross-reacts
      with an anti-human ACAT-2 antibody. The tissue distribution of rat ACAT-2 mRNA
      revealed its restricted expression to liver and small intestine.
      Immunohistochemical analyses using an anti-human ACAT-2 antibody demonstrated
      that ACAT-2 is localized in villus-crypt axis of rat small intestine. The
      intestinal ACAT activity in diabetic rats was significantly immunodepleted by an
      anti-ACAT-2 antibody but not by an anti-ACAT-1 antibody. Finally, intestinal ACAT
      2 in diabetic rats significantly increased at both protein and mRNA levels as
      compared with that in control rats. CONCLUSIONS: Our data demonstrate that ACAT-2
      isozyme is responsible for the increased intestinal ACAT activity of diabetic
      rats, suggesting an important role of ACAT-2 for dyslipidemia in diabetic
      patients. Diabetic rats exhibit dyslipidemia caused, in part, by elevated
      intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. We
      determined which ACAT isozyme (ACAT-1 or ACAT-2) was involved in the elevated
      intestinal ACAT activity in diabetic rats. We demonstrated an important role of
      ACAT-2, implicating its involvement in dyslipidemia in diabetic patients.

PMID- 15242860
TI  - cAMP-response element-binding protein mediates tumor necrosis factor-alpha
      induced vascular smooth muscle cell migration.
AB  - OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) contributes to
      formation of vascular stenotic lesions such as atherosclerosis and restenosis
      after angioplasty. Previous studies have demonstrated that tumor necrosis factor
      alpha (TNF-alpha) is a potent migration factor for VSMCs. cAMP-response element
      binding protein (CREB) is the stimulus-induced transcription factor and activates
      transcription of target genes such as c-fos and interleukin-6. We examined
      whether CREB is involved in TNF-alpha-induced VSMC migration. METHODS AND
      RESULTS: TNF-alpha induced CREB phosphorylation with a peak at 15 minutes of
      stimulation. Pharmacological inhibition of p38 mitogen-activated protein kinase
      (p38-MAPK) inhibited TNF-alpha-induced CREB phosphorylation. Adenovirus-mediated
      overexpression of dominant-negative form of CREB suppressed TNF-alpha-induced
      CREB phosphorylation and c-fos mRNA expression. VSMC migration was evaluated
      using a Boyden chamber. Overexpression of dominant-negative form of CREB
      suppressed VSMC migration as well as Rac1 expression induced by TNF-alpha.
      Overexpression of dominant-negative Rac1 also inhibited TNF-alpha-induced VSMC
      migration. CONCLUSIONS: Our results suggest that p38-MAPK/CREB/Rac1 pathway plays
      a critical role in TNF-alpha-induced VSMC migration and may be a novel
      therapeutic target for vascular stenotic lesion. Migration of vascular smooth
      muscle cells (VSMCs) contributes to formation of vascular stenotic lesions. TNF
      alpha, a potent migration factor for VSMCs, activated CREB through p38 mitogen
      activated protein kinase (p38-MAPK). CREB inhibition suppressed TNF-alpha-induced
      VSMC migration and Rac1 expression. These results suggest p38-MAPK/CREB/Rac1
      pathway mediates TNF-alpha-induced VSMC migration.

PMID- 15242861
TI  - Potential role for mitogen-activated protein kinase phosphatase-1 in the
      development of atherosclerotic lesions in mouse models.
AB  - OBJECTIVE: Mitogen-activated protein kinase phosphatase-1 (MKP-1) is one of
      several oxidized-l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3
      phosphorylcholine (Ox-PAPC)-induced genes identified in human aortic endothelial
      cells (HAEC). We previously reported that MKP-1 activity is required for Ox-PAPC
      mediated endothelial/monocyte interactions; however, an in vivo role of MKP-1 in
      atherogenesis has not been investigated. METHODS AND RESULTS: We now report that
      MKP-1 protein is expressed in the atherosclerotic lesions of mice. MKP-1 mRNA
      expression is highly induced in C57BL6/J mice on an atherogenic diet, low-density
      lipoprotein receptor (LDLR) (-/-) mice on a Western diet, and 10-week or older
      ApoE (-/-) mice on a chow diet. In ApoE (-/-) mice treated with 1 mg/mL of sodium
      orthovanadate (NaOV), a specific inhibitor of tyrosine phosphatases including MKP
      1, total phosphatase activity and MKP-1 protein were decreased in both the aortic
      lesions and liver lysates. In 3 animal models of atherosclerosis [C57BL6/J mice
      on an atherogenic diet for 15 weeks, LDLR (-/-) mice on a Western diet for 10
      weeks, and ApoE (-/-) mice on a chow diet for 8 weeks], mice treated with NaOV
      had significantly smaller atherosclerotic lesions when compared with the control
      group. CONCLUSIONS: MKP-1 expression is associated with hypercholesterolemia and
      atherosclerosis, and inhibition of MKP-1 activity may prevent atherosclerotic
      lesion development in mice. MKP-1 is required for Ox-PAPC-mediated
      endothelial/monocyte interactions; however, an in vivo role of MKP-1 in
      atherogenesis has not been investigated. We now report that MKP-1 protein is
      expressed in the atherosclerotic lesions of mice and inhibition of tyrosine
      phosphatase activity and MKP-1 protein reduce atherosclerotic lesions in mouse
      models.

PMID- 15242862
TI  - Homeobox protein Hex facilitates serum responsive factor-mediated activation of
      the SM22alpha gene transcription in embryonic fibroblasts.
AB  - OBJECTIVE: Hex (hematopoietically expressed homeobox), a member of homeobox
      family of transcription factors, has been implicated in the vascular development
      because of its expression in hemangioblast, a hypothetical stem cell that gives
      rise to both angioblasts and hematopoietic lineages. In the present study, we
      examined the role of Hex in the differentiation of vascular smooth muscle cells.
      METHODS AND RESULTS: We constructed adenovirus expressing Hex, to which we refer
      to as AxCA/Hex, and transduced murine embryonic fibroblasts, 10T1/2 cells.
      Northern blot analyses showed that Hex increased the mRNA levels of smooth muscle
      alpha-actin and SM22alpha but not of calponin and smooth muscle myosin heavy
      chain. Transient transfection assays showed that Hex activates the transcription
      from the SM22alpha promoter in a CArG box-dependent manner. Electrophoretic
      mobility shift assays demonstrate that Hex is not able to bind to CArG box, but
      binding of serum responsive factor (SRF) to CArG box is enhanced in AxCA/Hex
      transduced cells. Recombinant Hex protein produced by in vitro translation system
      augmented the binding activity of SRF to CArG box. Immunoprecipitation
      experiments revealed the physical association between Hex and SRF. CONCLUSIONS:
      Hex induces transcription of the SM22alpha gene by facilitating the interaction
      between SRF and its cognate binding site in pluripotent embryonic fibroblasts.
      This study demonstrates that Hex, a hematopoietically expressed homeobox protein,
      induces transcription of the SM22alpha gene by facilitating the interaction
      between SRF and its cognate binding site in embryonic fibroblasts. These findings
      will provide the clue for understanding the mechanisms by which bone marrow
      derived SMC precursor cells undergo differentiation.

PMID- 15242863
TI  - Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and
      B-100 kinetics using stable isotopes.
AB  - OBJECTIVE: Our purpose was to determine the relationship between apolipoprotein
      (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic
      humans. METHODS AND RESULTS: The kinetics of apoA-I within high-density
      lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins,
      and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein
      (LDL) were examined with a primed constant infusion of [5,5,5-(2)H(3)] leucine in
      the fed state (hourly feeding) in 23 subjects after consumption of a 36% total
      fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by
      SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass
      spectrometry. Kinetic parameters were calculated by multicompartmental modeling
      of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL
      apoB-100 pool size (PS; r=0.49; P=0.017) and LDL cholesterol (r=0.61; P=0.002),
      whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB
      48 FCR (r=-0.40; P=0.05) but not with very low-density lipoprotein apoB-100 FCR.
      CONCLUSIONS: Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB
      100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant
      clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a
      finding indicating that alterations in intestinal lipoproteins may be more
      important in determining HDL cholesterol levels than changes in liver
      lipoproteins. Using stable isotopes in humans, 2 links were observed between apoA
      I and apoB kinetics: (1) when LDL apoB-100 PS is high, there is increased apoA-I
      PR; and (2) delayed chylomicron remnant clearance is associated with enhanced
      apoA-I FCR, indicating that alterations in intestinal lipoproteins may be more
      important in determining HDL-C levels than changes in liver lipoprotein
      particles.

PMID- 15242864
TI  - Elevated fluid shear stress enhances postocclusive collateral artery growth and
      gene expression in the pig hind limb.
AB  - OBJECTIVE: The role of fluid shear stress (FSS) in collateral vessel growth
      remains disputed and prospective in vivo experiments to test its morphogenic
      power are rare. Therefore, we studied the influence of FSS on arteriogenesis in a
      new model with extremely high levels of collateral flow and FSS in pig and rabbit
      hind limbs. METHODS AND RESULTS: A side-to-side anastomosis was created between
      the distal stump of one of the bilaterally occluded femoral arteries with the
      accompanying vein. This clamps the collateral reentry pressure at venous levels
      and increases collateral flow, which is directed to a large part into the venous
      system. This decreases circumferential wall stress and markedly increases FSS.
      One week after anastomosis, angiographic number and size of collaterals were
      significantly increased. Maximal collateral flow exceeded by 2.3-fold that
      obtained in the ligature-only hind limb. Capillary density increased in lower leg
      muscles. Immunohistochemistry revealed augmented proliferative activity of
      endothelial and smooth muscle cells. Intercellular adhesion molecule-1 and
      vascular cell adhesion molecule (VCAM)-1 were upregulated, and monocyte invasion
      was markedly increased. In 2-dimensional gels, actin-regulating cofilin1 and
      cofilin2, destrin, and transgelin2 showed the highest degree of differential
      regulation. CONCLUSIONS: High levels of FSS cause a strong arteriogenic response,
      reinstate cellular proliferation, stimulate cytoskeletal rearrangement, and
      normalize maximal conductance. FSS is the initiating molding force in
      arteriogenesis. The role of fluid shear stress on the development of a collateral
      circulation was studied by abruptly increasing collateral blood flow by a distal
      femoral artery-to-vein anastomosis. This increased number and size of collateral
      vessels to a hitherto unknown degree. Fluid shear stress is the primary and
      strongest arteriogenic stimulus.

PMID- 15242865
TI  - A multicentre, randomised, double blind, placebo controlled phase II study of
      subcutaneous interferon beta-1a in the treatment of patients with active
      rheumatoid arthritis.
AB  - OBJECTIVE: To assess the efficacy of interferon beta (IFN beta) in combination
      with methotrexate in treatment of patients with rheumatoid arthritis. METHODS:
      209 patients with active rheumatoid arthritis, who had been on methotrexate for
      at least six months and at a stable dose for four weeks before study entry, were
      randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN
      beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously
      three times weekly for 24 weeks. The primary efficacy measure was a change in
      radiological scores at week 24. The secondary endpoint was the proportion of
      patients who met the ACR 20% improvement criteria at the end of the study.
      Synovial biopsy specimens were obtained before and after treatment from a subset
      of patients. Immunohistochemistry was used to detect the presence of inflammatory
      cells and the results were measured by digital image analysis. Collagen
      crosslinks were measured in urine at different times throughout the study.
      RESULTS: Analysis of radiological scores and clinical variable showed no changes
      in any of the groups, and there were no differences between the groups. On
      microscopic analysis of synovial tissue there was no significant change in the
      scores for infiltration by inflammatory cells after IFN beta treatment. Urinary
      levels of collagen crosslinks were unchanged between the treatment groups.
      CONCLUSIONS: At the doses tested, treatment with IFN beta three times weekly in
      combination with methotrexate did not have a clinical or radiological effect in
      patients with rheumatoid arthritis.

PMID- 15242866
TI  - Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on
      safety.
AB  - Anti-TNFalpha therapy may have associated risks of serious infection, congestive
      heart failure, malignancy, and multiple sclerosis. The magnitude of these risks
      is difficult to assess. This article reviews publications on the current
      knowledge about the safety of these agents.

PMID- 15242867
TI  - Randomised controlled trial assessing the impact of a nurse delivered, flow
      monitored protocol for optimisation of circulatory status after cardiac surgery.
AB  - OBJECTIVE: To assess whether a nurse led, flow monitored protocol for optimising
      circulatory status in patients after cardiac surgery reduces complications and
      shortens stay in intensive care and hospital. DESIGN: Randomised controlled
      trial. SETTING: Intensive care unit and cardiothoracic unit of a university
      teaching hospital. PARTICIPANTS: 174 patients who underwent cardiac surgery
      between April 2000 and January 2003. INTERVENTIONS: Patients were allocated to
      conventional haemodynamic management or to an algorithm guided by oesophageal
      Doppler flowmetry to maintain a stroke index above 35 ml/m2. RESULTS: 26 control
      patients had postoperative complications (two deaths) compared with 17 (four
      deaths) protocol patients (P = 0.08). Duration of hospital stay in the protocol
      group was significantly reduced from a median of nine (interquartile range 7-12)
      days to seven (7-10) days (P = 0.02). The mean duration of hospital stay was
      reduced from 13.9 to 11.4 days, a saving in hospital bed days of 18% (95%
      confidence interval -12% to 47%). Usage of intensive care beds was reduced by 23%
      (-8% to 59%). CONCLUSION: A nurse delivered protocol for optimising circulatory
      status in the early postoperative period after cardiac surgery may significantly
      shorten hospital stay.

PMID- 15242868
TI  - Hospital at home for patients with acute exacerbations of chronic obstructive
      pulmonary disease: systematic review of evidence.
AB  - OBJECTIVES: To evaluate the efficacy of hospital at home schemes compared with
      inpatient care in patients with acute exacerbations of chronic obstructive
      pulmonary disease (COPD). DESIGN: A systematic review of randomised controlled
      trials. MAIN OUTCOME MEASURE: Mortality and readmission to hospital. RESULTS:
      Seven trials with 754 patients were included in the review. Hospital readmission
      and mortality were not significantly different when hospital at home schemes were
      compared with inpatient care (relative risk 0.89, 95% confidence interval 0.72 to
      1.12, and 0.61, 0.36 to 1.05, respectively). However, compared with inpatient
      care, hospital at home schemes were associated with substantial cost savings as
      well as freeing up hospital inpatient beds. CONCLUSIONS: Hospital at home schemes
      can be safely used to care for patients with acute exacerbations of COPD who
      would otherwise be admitted to hospital. Clinicians should consider this form of
      management, especially as there is increasing pressure for inpatient beds in the
      United Kingdom.

PMID- 15242869
TI  - Characterization of acute lymphoblastic leukemia progenitor cells.
AB  - Only some acute lymphoblastic leukemia (ALL) cells are thought to be capable of
      proliferating to maintain the leukemic clone, and these cells may be the most
      relevant to target with treatment regimens. We have developed a serum-free
      suspension culture (SC) system that supported growth of B-ALL cells from 33
      patients for up to 6 weeks. ALL cells from 28 cases (85%) were expanded in this
      system, and growth was superior in SC than in long-term bone marrow culture. To
      characterize ALL progenitors, cells were sorted for expression of CD34 and CD10
      or CD19 and the subfractions assayed in SC and in nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. Cells capable of long-term
      proliferation in vitro and NOD/SCID repopulation were derived only from the
      CD34(+)/CD10(-) and CD34(+)/CD19(-) subfractions, and these cells could engraft
      secondary recipients. The engrafted cells had the same immunophenotype and
      karyotype as was seen at diagnosis, suggesting they had differentiated in vivo.
      These results demonstrate that ALL cells capable of long-term proliferation in
      vitro and in vivo are CD34(+)/CD10(-)/CD19(-). This suggests that cells with a
      more immature phenotype, rather than committed B-lymphoid cells, may be the
      targets for transformation in B-ALL.

PMID- 15242870
TI  - E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class
      II transactivator promoter III (CIITA-PIII).
AB  - In B cells, expression of CIITA and resulting major histocompatibility complex II
      (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent
      studies have established that CIITA-PIII also participates in the expression of
      CIITA in activated human T cells, dendritic cells, and monocytes. In this study
      we characterized the various regulatory elements and interacting factors of CIITA
      PIII that account for specific activation in B lymphocytes. We identified 2 E-box
      motifs and an Ets/ISRE-consensus element (EICE) in CIITA-PIII as playing a
      crucial role in the B-cell-specific transcriptional regulation of CIITA.
      Abolishment of factor binding to these elements resulted in a strong reduction of
      CIITA-PIII activation in B cells only, whereas it did scarcely affect or not
      affect the activity of CIITA-PIII in activated T cells and monocytes. We show
      that in B cells, E47 and PU.1/IRF-4 interact with the E-box motifs and the EICE,
      respectively, and act synergistically in the activation of CIITA-PIII. Moreover,
      functional inhibition of either E47 or IRF-4 resulted in strong reduction of
      CIITA-PIII activity in B lymphocytes only. The finding that PU.1, IRF-4, and E47
      play an important role in the B-cell-mediated activation of CIITA-PIII provides a
      link between antigen presentation functions and activation and differentiation
      events in B lymphocytes.

PMID- 15242871
TI  - NK cell activation by dendritic cells (DCs) requires the formation of a synapse
      leading to IL-12 polarization in DCs.
AB  - Mature dendritic cells (mDCs) can trigger the effector functions of natural
      killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies
      targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in
      NK cell interferon gamma (IFN-gamma) secretion promoted by mDCs. However, NK cell
      activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell
      activation involved the formation of stimulatory synapses between DCs and NK
      cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling
      and lipid raft mobilization in DCs. Moreover, the disruption of the DC
      cytoskeleton using pharmacologic agents or the loss-of-function mutation of the
      Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation.
      Synapse formation promoted the polarized secretion of preassembled stores of IL
      12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required
      for IFN-gamma secretion by NK cells, as assessed using inhibitors of cytoskeleton
      rearrangements and transwell experiments. Therefore, the cross-talk between DCs
      and NK cells is dictated by functional synapses.

PMID- 15242872
TI  - KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in
      sickle reticulocytes.
AB  - KCl cotransport (KCC) activation by cell swelling and pH was compared in sickle
      (SS) and normal (AA) red blood cells (RBCs). KCC fluxes had the same relationship
      to mean corpuscular hemoglobin concentration (MCHC) in SS and AA RBCs when
      normalized to the maximal volume-stimulated (VS(max)) flux (MCHC < 270 g/L [27
      g/dL]). Acid-stimulated (pH 6.9) KCC flux in SS RBCs was 60% to 70% of VS(max)
      KCC versus 20% in AA RBCs. Density gradients were used to track changes in
      reticulocyte MCHC during KCC-mediated regulatory volume decrease (RVD). Swelling
      to MCHC of 260 g/L (26 g/dL) produced Cl-dependent RVD that resulted in higher
      MCHC in SS than AA reticulocytes. In acid pH, RVD was also greater in SS than AA
      reticulocytes. Sulfhydryl reduction by dithiothreitol (DTT) lowered VS(max) KCC
      flux in AA and SS RBCs by one third but did not alter swelling-induced RVD. DTT
      lowered acid-activated KCC in SS RBCs by 50% and diminished acid-induced RVD in
      SS reticulocytes. Thus, swelling activation of KCC is normal in SS RBCs but KCC
      mediated RVD produces higher MCHC in SS than AA reticulocytes. Acid activation of
      KCC is exaggerated in SS RBCs and causes dehydration in SS reticulocytes. KCC
      response to acid stimulation was mitigated by DTT, suggesting that it arises from
      sulfhydryl oxidation.

PMID- 15242873
TI  - Suspended cells from trabecular bone by collagenase digestion become virtually
      identical to mesenchymal stem cells obtained from marrow aspirates.
AB  - Several reports describe that the explant culture of the trabecular bone after
      collagenase treatment produces mesenchymal stem cells (MSCs). However, the
      suspended cells had not been intensively examined concerning MSCs. We
      hypothesized that the cells would acquire the properties of MSCs during their
      expansion and therefore compared them with marrow aspirate-derived MSCs. Human
      trabecular bones were washed, digested, filtered, and expanded clonally for 14
      days. Their proliferation ability (n = 9) and differentiation potentials for
      chondrocyte, adipocyte, and osteoblast (n = 6) were similar with those of marrow
      aspirate-derived MSCs. Epitope and mRNA analysis revealed some differences in
      both types of cells, which disappeared with expansion and subcultivation. A mixed
      population of collagenase-released (CR) cells had similar differentiation
      potentials with CR clone, CD31(+) fraction, and osteoblastic cells. For
      quantitative study, trabecular bone and bone marrow were harvested by single
      aspiration using a biopsy needle (n = 16). Although the total nucleated cell
      number harvested was similar, the colony-forming efficiency of CR cells was
      approximately 100-fold higher than that of BM cells and more than 1 million CR
      cells could be obtained in 14 days from all donors. Enzymatically released cells
      from trabecular bone became virtually identical to marrow aspirate-derived MSCs,
      demonstrating that a trabecular bone fragment can be an alternative source of
      MSCs.

PMID- 15242874
TI  - Enhancement of stress-induced apoptosis in B-lineage cells by caspase-9
      inhibitor.
AB  - We have established human B-lineage (BLIN) acute lymphoblastic leukemia cell
      lines that retain a dependency on fibroblast monolayers for survival and
      proliferation. Eight hours following removal from adherent cell contact BLIN
      cells undergo a decrease in mitochondrial transmembrane potential and an increase
      in annexin V binding. Unexpectedly, the caspase-9 inhibitor (C9i)
      benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone enhanced the appearance of
      apoptotic cells within 8 hours following removal of BLIN cells from fibroblast
      monolayers. C9i enhancement of apoptosis was dose dependent and did not occur
      with irreversible inhibitors of caspases-2, -3, -6, and -8. C9i also enhanced
      apoptosis in cord blood-derived CD19(+) B-lineage cells (but not myeloid cells)
      removed from murine stromal cells. Longer exposure (> 18 hours) to C9i culminated
      in apoptosis in a panel of B-lineage acute lymphoblastic leukemia (ALL) cell
      lines in the presence or absence of fibroblast monolayers, as well as in 2
      proliferating leukemic cell lines (RAMOS and CEM). BLIN-4L cells made deficient
      in caspase-9 by RNA interference exhibited no resistance to apoptotic signals and
      actually showed increased apoptotic sensitivity to staurosporine. These
      collective results suggest that a 4-amino acid caspase inhibitor of caspase-9 can
      promote apoptosis and that at least some types of apoptotic pathways in B-lineage
      ALL do not require caspase-9.

PMID- 15242875
TI  - Apoptotic bodies from endothelial cells enhance the number and initiate the
      differentiation of human endothelial progenitor cells in vitro.
AB  - Endothelial progenitor cells (EPCs) play a role in the repair of ischemic or
      injured tissue. Because endothelial injury can be associated with apoptosis, we
      have investigated whether apoptotic bodies from mature endothelial cells (ECs)
      may affect growth and differentiation of EPCs in vitro. A 24-hour incubation of
      isolated human EPCs with apoptotic bodies-rich medium (ABRM) from ECs led to a
      significant increase in the number of spindle-shaped attached cells. EPCs were
      characterized by DiI-Ac-LDL/lectin staining and measurement of CD34 and kinase
      insert domain receptor (KDR) expression. The treatment with ABRM resulted in a 2
      fold increase of DiI-Ac-LDL/lectin-positive cells and up-regulation of CD34 (22%
      +/- 2% versus 13% +/- 3%, P < .05 and KDR (49% +/- 12% versus 19% +/- 7%, P <
      .05). Fluorescence and confocal laser microscopy demonstrated the uptake of
      apoptotic bodies by the EPCs. Apoptotic bodies-depleted medium had no effect,
      whereas the incubation with suspension of apoptotic bodies induced effects
      similar to those of ABRM. Our results suggest that apoptotic bodies from ECs are
      taken up by EPCs, increasing their number and differentiation state. Such a
      mechanism may facilitate the repair of injured endothelium and may represent a
      new signaling pathway between progenitor and damaged somatic cells.

PMID- 15242876
TI  - Leukocyte immunoglobulin-like receptors: novel innate receptors for human
      basophil activation and inhibition.
AB  - Basophils, recruited from the blood to tissues, have been implicated by their
      presence in diverse allergic disorders including bronchial asthma, allergic
      rhinitis, and cutaneous contact hypersensitivity. We hypothesized that like other
      leukocytes involved in inflammatory responses, basophils would express members of
      the leukocyte immunoglobulin-like receptor (LIR) family of immuno-regulatory
      molecules on their cell surface. We identified LIR7, an activating member coupled
      to the common Fc receptor gamma chain, and LIR3, an inhibitory member containing
      cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, on these cells from
      human peripheral blood. Cross-linking of LIR7 resulted in the concentration
      dependent net release of histamine (29.8 +/- 10.8%) and cysteinyl leukotrienes
      (cysLTs) (31.4 +/- 8.7 ng/10(6) basophils) that were maximal at 30 minutes, and
      of interleukin-4 (IL-4) (410.2 +/- 61.6 pg/10(6) basophils) that was maximal at 4
      hours and comparable with the response initiated by cross-linking of the high
      affinity receptor for immunoglobulin E (FcepsilonRI). Coligation of LIR3 to LIR7
      or to FcepsilonRI by means of a second monoclonal antibody significantly
      inhibited net histamine release, cysLT production, and IL-4 generation. That LIR3
      is profoundly counter-regulatory for both adaptive and innate receptors suggests
      a broad role in containment of the inflammatory response.

PMID- 15242877
TI  - BCL2 protein expression parallels its mRNA level in normal and malignant B cells.
AB  - The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center
      (GC) B cells has been controversial. Previous reports have indicated
      posttranscriptional regulation plays a dominant role. However, a number of recent
      studies contradicted these reports. Using real-time polymerase chain reaction
      (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the
      level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells
      from laser capture microdissection. Both quantitative RT-PCR measurements of
      microdissected GC cells from tonsils showed that GC cells had low expression of
      BCL2 transcripts commensurate with the low protein expression level. These
      results are in agreement with microarray studies on fluorescence-activated cell
      sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2
      mRNA and protein expression on a series of 30 cases of diffuse large B-cell
      lymphoma (DLBCL) and found, in general, a good correlation. The results suggested
      that BCL2 protein expression is regulated at the transcriptional level in normal
      B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.

PMID- 15242878
TI  - Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in
      plasmas of patients with the antiphospholipid syndrome.
AB  - Annexin A5 (A5) forms 2-dimensional crystals over phospholipid bilayers, blocking
      their availability for coagulation reactions. Recently, human antiphospholipid
      (aPL) monoclonal antibodies (mAbs) have been demonstrated by atomic force
      microscopy (AFM) to disrupt this crystallization and accelerate coagulation. We
      therefore performed a study with small, well-defined groups of patients to
      investigate whether these effects on A5 binding and activity are also detectable
      in plasmas from patients with the aPL syndrome. A5 binding to phospholipid was
      significantly reduced by plasmas of patients with the aPL syndrome and
      thromboembolism compared with healthy controls (mean +/- SD, 26.7 +/- 4.3 ng/well
      [n = 25] vs 30.5 +/- 3.1 ng/well [n = 20], P < .01) and the non-aPL
      thromboembolism group (29.9 +/- 3.2 ng/well [n = 15], P < .05). A5 anticoagulant
      activity was reduced by plasmas of patients with aPL syndrome and thromboembolism
      compared with aPL antibodies without thrombosis (182 +/- 31% [n = 25] vs 210 +/-
      35% [n = 26], P < .01), non-aPL thromboembolism (229 +/- 16% [n = 15], P < .001),
      and healthy controls (231 +/- 14% [n = 30], P < .001). In conclusion, in
      accordance with recent AFM data with monoclonal human aPL antibodies, plasmas
      from patients with aPL antibodies with thromboembolism reduce both A5 binding to
      phospholipid and A5 anticoagulant activity. This "annexin A5 resistance"
      identifies a novel mechanism for thrombosis in the aPL syndrome.

PMID- 15242880
TI  - Paxillin selectively associates with constitutive and chemoattractant-induced
      high-affinity alpha4beta1 integrins: implications for integrin signaling.
AB  - Leukocyte alpha4beta1 integrins regulate hematopoietic and lymphoid development,
      as well as the emigration of circulating cells to sites of inflammation. Because
      vascular cell adhesion molecule-1 (VCAM-1) binding to high-affinity alpha4beta1
      is stable, these integrins can be detected and selectively precipitated from cell
      lysates using VCAM-1/Fc. With this approach, high-affinity alpha4beta1 integrin
      expression was demonstrated on lymphocytes in the bone marrow, thymus, spleen,
      and the peritoneal cavity of normal mice, but not in peripheral lymph nodes.
      Immature lymphocytes preferentially expressed high-affinity alpha4beta1 in the
      bone marrow and thymus. Paxillin is a cytoplasmic adaptor molecule that can bind
      to the alpha4 tail and initiate signaling. Paxillin was associated selectively
      with high-affinity integrins that were isolated from human Jurkat T cells or from
      murine tissues, and blotting with a phospho-specific antibody demonstrated that
      Ser988 in the alpha4 cytoplasmic tail was dephosphorylated in high-affinity but
      not low-affinity integrins. A rapid and transient alpha4beta1 affinity up
      regulation in formyl peptide receptor-transfected U937 cells stimulated with N
      formyl-methyonyl-leucyl-phenylalanine (fMLP) correlated temporally with induced
      paxillin binding to alpha4 integrins. These data suggest that ligand binding to
      high-affinity alpha4beta1 integrins may initiate outside-in signaling cascades
      through paxillin that regulate leukocyte maturation and emigration.

PMID- 15242879
TI  - Enforced expression of an Flt3 internal tandem duplication in human CD34+ cells
      confers properties of self-renewal and enhanced erythropoiesis.
AB  - To investigate the role of constitutively active internal tandem duplication
      (ITD) mutants of the Fms-like tyrosine kinase 3 (Flt3) receptor in
      leukemogenesis, we introduced the Flt3-ITD, W51, into human cord blood CD34+
      cells and evaluated their phenotype in diverse hematopoietic assays. W51
      expression resulted in a strong proliferative advantage and enhanced
      erythropoiesis as determined by immunophenotyping, colony assays, and molecular
      analyses. In MS-5 stromal cocultures, numerous early cobblestone areas (CAs) were
      generated within 10 to 14 days. Such W51-associated early CAs disappeared by 4
      weeks, yet retained self-renewal properties as demonstrated by generation of
      secondary and tertiary CAs upon replating. This phenotype appears related to the
      expression of W51 since it was abolished by exposure to the FLT3 inhibitor,
      AG1295, but not to the c-kit inhibitor PD16. Wild-type Flt3-overexpressing CD34+
      cells exposed to high levels of its physiologic ligand did not produce early CAs,
      highlighting differences in intracellular signaling between wild-type Flt3 and
      W51. W51-associated signal transducer and activator of transcription 5 (Stat5)
      activation plays a major role in this phenotype, although additional downstream
      targets of W51 may be relevant. Flt3-ITD+ acute myeloid leukemia (AML) blasts
      from patients invariably generated early AG1295-sensitive CAs in MS-5 cocultures,
      further validating the phenotype observed in transduced CD34+ cells.

PMID- 15242881
TI  - Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant
      hematopoiesis.
AB  - Internal tandem duplications (ITDs) of the FMS-like tyrosine kinase 3 (FLT3)
      receptor tyrosine kinase are found in approximately 30% of patients with acute
      myelogenous leukemia (AML) and are associated with a poor prognosis. FLT3 ITD
      mutations result in constitutive kinase activation and are thought to be
      pathogenetically relevant, implicating FLT3 as a plausible therapeutic target.
      MLN518 (formerly CT53518) is a small molecule inhibitor of the FLT3, KIT, and
      platelet-derived growth-factor receptor (PDGFR) tyrosine kinases with significant
      activity in murine models of FLT3 ITD-positive leukemia. Given the importance of
      FLT3 and KIT for normal hematopoietic progenitor cells, we analyzed the effect of
      MLN518 on murine hematopoiesis under steady-state conditions, after chemotherapy
      induced myelosuppression, and during bone marrow transplantation. In these
      assays, we show that MLN518 has mild toxicity toward normal hematopoiesis at
      concentrations that are effective in treating FLT3 ITD-positive leukemia in mice.
      We also demonstrate that MLN518 preferentially inhibits the growth of blast
      colonies from FLT3 ITD-positive compared with ITD-negative patients with AML, at
      concentrations that do not significantly affect colony formation by normal human
      progenitor cells. In analogy to imatinib mesylate in BCR-ABL-positive acute
      leukemia, MLN518-induced remissions may not be durable. Our studies provide the
      basis for integrating this compound into chemotherapy and transplantation
      protocols.

PMID- 15242883
TI  - Patient choice in the NHS.

PMID- 15242882
TI  - The phenotype of motor neuropathies associated with BSCL2 mutations is broader
      than Silver syndrome and distal HMN type V.
AB  - Silver syndrome is a rare autosomal dominant neurodegenerative disorder
      characterized by marked amyotrophy and weakness of small hand muscles and
      spasticity in the lower limbs. The locus for Silver syndrome (SPG17) was assigned
      to a 13 cM region on chromosome 11q12-q14 in a single large pedigree. We recently
      found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy
      (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V
      (distal HMN V). Here we report the clinical features of two families with
      heterozygous BSCL2 mutations. Interestingly, both families show a clinical
      phenotype different from classical Silver syndrome, and in some patients the
      phenotype is also different from distal HMN V. Patients in the first family had
      marked spasticity in the lower limbs and very striking distal amyotrophy that
      always started in the legs. Patients in the second family had distal amyotrophy
      sometimes starting and predominating in the legs, but no pyramidal tract signs.
      These observations broaden the clinical phenotype of disorders associated with
      BSCL2 mutations, having consequences for molecular genetic testing.

PMID- 15242884
TI  - Non-parenteral vaccines.

PMID- 15242885
TI  - Transplantation for alcoholic liver disease.

PMID- 15242886
TI  - Open access to industry's clinically relevant data.

PMID- 15242887
TI  - Doctors and the war on terrorism.

PMID- 15242888
TI  - HIV/AIDS is spreading fastest in eastern Europe and Asia.

PMID- 15242891
TI  - Netherlands plans system for reporting errors.

PMID- 15242893
TI  - Screening for sickle cell disease and thalassaemia saving lives.

PMID- 15242892
TI  - Whistleblower charges medical oversight bureau with corruption.

PMID- 15242894
TI  - Nigerian state of Kano resumes polio vaccination.

PMID- 15242897
TI  - BMA demands ban on smoking in enclosed workplaces in the United Kingdom.

PMID- 15242902
TI  - Woman forced to have three embryos implanted is allowed fetal reduction to save
      her life.

PMID- 15242911
TI  - US to introduce new rules on air pollution.

PMID- 15242914
TI  - Reform of undergraduate medical teaching in the United Kingdom: a triumph of
      evangelism over common sense.

PMID- 15242915
TI  - Common skin infections in children.

PMID- 15242916
TI  - Avulsion fracture of the ischial tuberosity in adolescents--an easily missed
      diagnosis.

PMID- 15242917
TI  - Initial management of a major burn: II--assessment and resuscitation.

PMID- 15242918
TI  - British American Tobacco and Formula One motor racing.

PMID- 15242919
TI  - Star wars, NHS style.

PMID- 15242920
TI  - Performance assessment is here to stay.

PMID- 15242921
TI  - Representation of authors and editors from poor countries: quality medical
      research from poor countries could be privileged in high impact journals.

PMID- 15242922
TI  - Representation of authors and editors from poor countries: partnerships may well
      be unequal.

PMID- 15242923
TI  - Representation of authors and editors from poor countries: observed publication
      bias may reflect who is funding research.

PMID- 15242924
TI  - Raised cardiac troponins: troponins seem to be sensitive but not specific.

PMID- 15242925
TI  - Raised cardiac troponins: troponin is raised in pre-eclampsia.

PMID- 15242926
TI  - Brief lifestyle interventions for hypertension: opportunity to provide useful
      information has been missed.

PMID- 15242927
TI  - Treatment of hepatic encephalopathy: it's not lactulose.

PMID- 15242928
TI  - Patient organisations in ME and CFS seek only understanding.

PMID- 15242934
TI  - Targeting CD40L: a promising therapeutic approach.

PMID- 15242935
TI  - Current advances in dengue diagnosis.

PMID- 15242936
TI  - Enzyme-linked immunosorbent assays using recombinant envelope protein expressed
      in COS-1 and Drosophila S2 cells for detection of West Nile virus immunoglobulin
      M in serum or cerebrospinal fluid.
AB  - Humans infected with West Nile virus (WNV) develop immunoglobulin M (IgM)
      antibodies soon after infection. The microtiter-based assays for WNV IgM antibody
      detection used by most state public health and reference laboratories utilize WNV
      antigen isolated from infected Vero cells or recombinant envelope protein
      produced in COS-1 cells. Recombinant antigen produced in COS-1 cells was used to
      develop a WNV IgM capture enzyme immunoassay (EIA). A supplementary EIA using WNV
      envelope protein expressed in Drosophila melanogaster S2 cells was also
      developed. Both assays detected WNV IgM in the sera of experimentally infected
      rhesus monkeys within approximately 10 days postinfection. Human sera previously
      tested for WNV IgM at a state public health laboratory (SPHL) were evaluated
      using both EIAs. Among the sera from 20 individuals with laboratory-confirmed WNV
      infection (i.e., IgM-positive cerebrospinal fluid [CSF]) that were categorized as
      equivocal for WNV IgM at the SPHL, 19 were IgM positive and one was negative by
      the new EIAs. Of the 19 IgM-positive patients, 15 were diagnosed with meningitis
      or encephalitis; the IgM-negative patient was not diagnosed with neurological
      disease. There was 100% agreement between the EIAs for the detection of WNV IgM.
      CSF samples from 21 individuals tested equivocal for WNV IgM at the SPHL; all 21
      were positive in both bead assays, and 16 of these patients were diagnosed with
      neurological disease. These findings demonstrate that the new EIAs accurately
      identify WNV infection in individuals with confirmed WNV encephalitis and that
      they exhibit enhanced sensitivity over that of the microtiter assay format.

PMID- 15242937
TI  - Characterization of immunodominant linear B-cell epitopes on the carboxy terminus
      of the rinderpest virus nucleocapsid protein.
AB  - The nucleocapsid (N) protein of rinderpest virus (RPV) is one of the most
      abundant and immunogenic viral proteins expressed during natural or experimental
      infection. To identify immunogenic epitopes on the N protein, different forms of
      RPV N protein, including the full-length protein (N(1-525)), an amino-terminal
      construct (N(1-179)), and a carboxy-terminal construct (N(414-496)), were
      expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins.
      The antigenicity of each recombinant protein was evaluated by Western
      immunoblotting. All recombinants were recognized by hyperimmune RPV bovine
      antisera, indicating that immunoreactive epitopes may be present at both ends of
      the N protein. However, GST-N(414-496) was much more antigenic than GST-N(1-179)
      when tested with sera from vaccinated cattle, suggesting that an immunodominant
      or highly immunogenic epitope(s) may be located at the carboxy terminus of the N
      protein. Epitope mapping with overlapping peptides representing different regions
      of the carboxy terminus (amino acids 415 to 524) revealed three nonoverlapping
      antigenic sites in regions containing the residues (440)VPQVRKETRASSR(452) (site
      1), (479)PEADTDPL(486) (site 2), and (520)DKDLL(524) (site 3). Among these,
      antigenic site 2 showed the strongest reactivity with hyperimmune anti-RPV bovine
      sera in a peptide enzyme-linked immunosorbent assay but did not react with
      hyperimmune caprine sera raised against peste-des-petits-ruminants virus, which
      is antigenically closely related to RPV. Identification of an immunodominant
      linear antigenic site at the carboxy terminus of the N protein may provide an
      antigen basis for designing diagnostics specific for RPV.

PMID- 15242938
TI  - Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against
      the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in
      patients with pneumonia due to the SARS coronavirus.
AB  - By using a recombinant severe acute respiratory syndrome coronavirus (SARS-CoV)
      nucleocapsid protein-based enzyme-linked immunosorbent assay (ELISA) and serum
      specimens serially collected (from day 0 to day 240 after symptom onset) from
      patients with pneumonia due to SARS-CoV, we analyzed the longitudinal profiles of
      immunoglobulin G (IgG), IgM, and IgA antibodies against the SARS-CoV nucleocapsid
      protein in patients with pneumonia due to SARS-CoV. For IgG, the median optical
      density at 450 nm (OD450) turned positive at day 17 and a biphasic response was
      observed. At day 240, all patients were still positive for anti-nucleocapsid
      protein IgG antibody. For IgM, the median OD450 turned positive at day 20.5,
      peaked at about day 80, and fell to below the baseline level at about day 180. At
      day 240, 36% of the patients were still positive for anti-nucleocapsid protein
      IgM antibody. For IgA, the median OD450 turned positive at day 17, peaked at
      about day 50, and fell to below the baseline level at about day 180. At day 240,
      36% of the patients were still positive for anti-nucleocapsid protein IgA
      antibody. The time of seroconversion detected by the recombinant SARS-CoV
      nucleocapsid protein-based ELISA and that detected by indirect immunofluorescence
      assay were similar. The median times of seroconversion for IgG, IgM, and IgA
      detected by the indirect immunofluorescence assay were 17 days (17 days by
      ELISA), 16.5 days (20.5 days by ELISA), and 17.5 days (17 days by ELISA),
      respectively, after disease onset. One, four, and one of the six patients who
      died did not produce any IgG, IgM, and IgA antibodies against the nucleocapsid
      protein of SARS-CoV, respectively, although these antibodies were detected in all
      six patients by the indirect immunofluorescence assay. Further studies should be
      performed to see whether SARS-CoV nucleocapsid protein antibody positivity has
      any prognostic significance.

PMID- 15242939
TI  - Reliability of immunoglobulin G antitoxoplasma avidity test and effects of
      treatment on avidity indexes of infants and pregnant women.
AB  - The immunoglobulin G antitoxoplasma avidity test (Vidas; BioMerieux) is an
      immunoenzymatic test useful for excluding acute infection after the onset of
      pregnancy. The avidity index (AI) is the ratio of the signal in a test sample
      washed with urea, which disrupts low-avidity complexes, to that washed without
      urea. An AI of >0.3 is taken to mean that infection had occurred more than 4
      months ago. The increase of the AI with time and the influence of the different
      treatments given to pregnant women and their newborns were evaluated. A total of
      59 pregnant women (271 sera) and their 60 neonates (199 sera) were tested from
      1998 to 2002. There were five groups of women based on the type and duration of
      treatment given. Thirteen pregnant women (group 1) did not receive any treatment,
      15 (group 2), 11 (group 3), and 17 (group 4) women received treatment with
      spiramycin (9 MIU/day) for 0.5 to 2, 2.5 to 5, and 5.5 to 8 months, respectively,
      and the last 3 women (group 5) received tritherapy (pyrimethamine-sulfonamide and
      spiramycin alternatively) for 1.5 to 2.5 months. All of the maternal sera
      collected in the first 6 months had an AI of <0.30, with a mean of 0.07 (range,
      0.01 to 0.21). The increase was slow (0.02/month), and there was no significant
      difference when comparisons were made between the treatment groups. Neonates with
      proven maternofetal transmission had an increasing AI, unlike those without
      transmission. However, long-term therapy with pyrimethamine-sulfonamide, as
      opposed to treatment with spiramycin alone, was found to slow down the
      progression of the AI. An AI of >0.2 is sufficient to exclude acute infection in
      pregnant women. In neonates, it is not of major use to diagnose congenital
      infection; however, it could be a good indicator of compliance and efficacy of
      treatment of infected infants.

PMID- 15242940
TI  - Reduction of influenza virus titer and protection against influenza virus
      infection in infant mice fed Lactobacillus casei Shirota.
AB  - We investigated whether oral administration of Lactobacillus casei strain Shirota
      to neonatal and infant mice ameliorates influenza virus (IFV) infection in the
      upper respiratory tract and protects against influenza infection. In a model of
      upper respiratory IFV infection, the titer of virus in the nasal washings of
      infant mice administered L. casei Shirota (L. casei Shirota group) was
      significantly (P < 0.05) lower than that in infant mice administered saline
      (control group) (10(2.48) +/- 10(0.31) and 10(2.78) +/- 10(0.4), respectively).
      Further, the survival rate of the L. casei Shirota group was significantly (P <
      0.05) higher than that of the control group (14.3 versus 40.0%). One day after
      infection, pulmonary NK cell activity and interleukin-12 production by
      mediastinal lymph node cells of mice in the L. casei Shirota group were
      significantly greater than those of mice in the control group. These findings
      suggest that oral administration of L. casei Shirota activates the immature
      immune system of neonatal and infant mice and protects against IFV infection.
      Therefore, oral administration of L. casei Shirota may accelerate the innate
      immune response of the respiratory tract and protect against various respiratory
      infections in neonates, infants, and children, a high risk group for viral and
      bacterial infections.

PMID- 15242941
TI  - Allergenic characterization of tropomyosin from the dusky brown cockroach,
      Periplaneta fuliginosa.
AB  - Household arthropods are one of the most common causes of allergic diseases. Four
      species of cockroaches are found to reside in Korean homes, but published work
      deals almost exclusively with the German and American cockroaches. This study was
      undertaken to investigate the cross-reactive allergenic components of the dusky
      brown cockroach, Periplaneta fuliginosa. Enzyme-linked immunosorbent assay
      (ELISA) inhibition and immunoblot analyses for the dusky brown cockroach were
      performed with Blattella germanica and Dermatophagoides farinae allergic sera.
      cDNA encoding tropomyosin, which is a well known cross-reactive pan-allergen, was
      cloned by reverse transcriptase PCR, and recombinant protein was produced by
      using a pET-28b expression system. Native tropomyosin was purified by ammonium
      sulfate fractionation and electroelution. The immunoglobulin E (IgE) reactivities
      of native and recombinant tropomyosins were compared by an ELISA inhibition
      study. All 30 sera tested showed P. fuliginosa-specific IgE, and the IgE-binding
      reactivity of the P. fuliginosa extract was inhibited as much as 79.4% by a B.
      germanica extract and as much as 63.3% by a D. farinae extract. The deduced amino
      acid sequence of cloned cDNA was identical with that of Periplaneta americana
      tropomyosin (98.5% nucleotide sequence identity). Seven of 26 (26.9%) allergic
      sera had IgE specific for recombinant protein, and the maximum inhibition of P.
      fuliginosa-specific IgE achieved with recombinant tropomyosin was 37.7% at an
      inhibitor concentration of 10 microg/ml. Native tropomyosin inhibited the binding
      of IgE to the P. fuliginosa, B. germanica, and D. farinae extracts by 65.0, 51.8,
      and 39% at an inhibitor concentration of 1 microg/ml. P. fuliginosa appears to
      possess allergens that are highly cross-reactive with allergens of B. germanica
      and D. farinae. Tropomyosin was found to be a major allergenic component
      accounting for the cross-reactivity between cockroaches and dust mites.

PMID- 15242942
TI  - Bifidobacterial species differentially affect expression of cell surface markers
      and cytokines of dendritic cells harvested from cord blood.
AB  - The gut microbiota may be important in the postnatal development of the immune
      system and hence may influence the prevalence of atopic diseases. Bifidobacteria
      are the most numerous bacteria in the guts of infants, and the presence or
      absence of certain species could be important in determining the geographic
      incidence of atopic diseases. We compared the fecal populations of bifidobacteria
      from children aged 25 to 35 days in Ghana (which has a low prevalence of atopy),
      New Zealand, and the United Kingdom (high-prevalence countries). Natal origin
      influenced the detection of bifidobacterial species in that fecal samples from
      Ghana almost all contained Bifidobacterium infantis whereas those of the other
      children did not. Choosing species on the basis of our bacteriological results,
      we tested bifidobacterial preparations for their effects on cell surface markers
      and cytokine production by dendritic cells harvested from cord blood. Species
      specific effects on the expression of the dendritic-cell activation marker CD83
      and the production of interleukin-10 (IL-10) were observed. Whereas CD83
      expression was increased and IL-10 production was induced by Bifidobacterium
      bifidum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum, B.
      infantis failed to produce these effects. We concluded that B. infantis does not
      trigger the activation of dendritic cells to the degree necessary to initiate an
      immune response but that B. bifidum, B. longum, and B. pseudocatenulatum induce a
      Th2-driven immune response. A hypothesis is presented to link our observations to
      the prevalence of atopic diseases in different countries.

PMID- 15242943
TI  - Development of a macroarray to specifically analyze immunological gene expression
      in swine.
AB  - DNA arrays are useful tools for simultaneously studying the expressions of a
      large number of genes. Herein, we describe the construction and the optimization
      of conditions for a low-density DNA macroarray specific for the porcine immune
      system. This specific DNA macroarray contains 63 gene products, including 20
      cytokines, 11 chemokines, and 12 immunologically relevant receptors. It was
      constructed by designing gene-specific oligonucleotide primers from porcine
      sequences available in the EMBL or TIGR expressed sequence tag data bank and
      using primers from conserved regions of aligned sequences from other species for
      sequences unavailable for swine. Amplicons produced by reverse transcription-PCR
      were cloned, sequenced, and spotted onto nylon filters. A trial DNA array was
      first produced to optimize the intensity, specificity, and variability of signals
      from amplicons amplified with either gene-specific or universal primers. The DNA
      macroarray was then validated by comparing the gene expression profile of
      nonstimulated peripheral blood mononuclear cells (PBMCs) to that of phorbol 12
      myristate 13-acetate and ionomycin (PMA-Iono)-stimulated PBMCs from three
      different animals over a 48-h time period. As already described for more
      conventional techniques, we showed that certain genes, such as those for CD40,
      gamma interferon, interleukin 2 (IL-2), the IL-2 receptor, and tumor necrosis
      factor alpha, were upregulated in PMA-Iono-stimulated PBMCs. A detailed analysis
      also indicated a downregulation of several genes which are expressed mainly by
      macrophages (IL-1, IL-8, AMCF-1, natural-resistance-associated macrophage
      protein, neutrophil chemotactic protein, DAP-12, and monocyte chemoattractant
      protein) in samples stimulated for 24 h with PMA-Iono compared to their levels of
      expression in control samples. These results indicate that the DNA macroarray
      that we constructed can be a useful tool for simultaneously monitoring the mRNA
      expression of immunologically relevant genes in different porcine samples.

PMID- 15242944
TI  - Evaluation and validation of an enzyme-linked immunosorbent assay and an
      immunochromatographic test for serological diagnosis of severe acute respiratory
      syndrome.
AB  - A newly developed severe acute respiratory syndrome (SARS)-specific enzyme-linked
      immunosorbent assay (ELISA) was further validated to confirm cutoff values and
      evaluate its diagnostic performance with clinical samples. In parallel, an
      immunochromatographic test was also evaluated. A total of 227 clinical serum
      specimens collected from SARS patients were used in the study, together with 385
      samples from healthy donors. By use of an immunofluorescent (IF) test as the
      "gold standard", both the ELISA and the immunochromatographic test were able to
      detect immunoglobulin G antibodies to SARS not only from late-convalescent-stage
      samples (>21 days from the onset of clinical symptoms), as previously
      established, but also from early-acute-phase samples (1 to 10 days from onset).
      The ELISA, using an optical density (OD) of 0.25 as its cutoff value, produced
      the best sensitivity while maintaining high specificity. It detected SARS
      specific antibodies in 58, 70, 75, and 95%, respectively, of the four groups of
      samples collected from patients 1 to 10 days, 11 to 20 days, 21 to 30 days, and
      more than 30 days after the onset of clinical symptoms. Similarly, the
      immunochromatographic test detected SARS-specific antibodies in 55, 68, 81, and
      79% of the four groups, respectively. The overall specificities for the ELISA and
      the rapid test were 99.5 and 97.7%, respectively. Although the positive
      correlation observed between the ELISA OD values and the IF titers was moderate
      (r = 0.6915; P < 0.001), the detection rates of both the ELISA and the rapid test
      were found well in agreement with the IF titers.

PMID- 15242945
TI  - Recombinant GRA4 or ROP2 protein combined with alum or the gra4 gene provides
      partial protection in chronic murine models of toxoplasmosis.
AB  - The efficacy of vaccination with Toxoplasma gondii recombinant GRA4 (rGRA4) and
      ROP2 (rRPO2) proteins and a mix of both combined with alum were evaluated in
      C57BL/6 and C3H mice. In C57BL/6 mice, rGRA4 and rGRA4-rROP2 immunizations
      generated similar levels of immunoglobulin G1 (IgG1) and IgG2a isotypes against
      GRA4, whereas immunizations with rROP2 and the mix induced a predominant IgG1
      production against ROP2. All groups of C3H vaccinated mice exhibited higher
      levels of IgG1 than IgG2a. rGRA4-stimulated splenocytes from vaccinated mice
      produced primarily gamma interferon while those stimulated with rROP2 produced
      interleukin-4. Challenge of rGRA4- or rGRA4-rROP2-vaccinated mice from both
      strains with ME49 cysts resulted in fewer brain cysts than the controls, whereas
      vaccination with rROP2 alone only conferred protection to C3H mice. Immunization
      with a plasmid carrying the entire open reading frame of GRA4 showed a protective
      level similar to that of rGRA4 combined with alum. These results suggest that
      GRA4 can be a good candidate for a multiantigen anti-T. gondii vaccine based on
      the use of alum as an adjuvant.

PMID- 15242946
TI  - Cholera toxin B-subunit gene enhances mucosal immunoglobulin A, Th1-type, and
      CD8+ cytotoxic responses when coadministered intradermally with a DNA vaccine.
AB  - A plasmid vector encoding the cholera toxin B subunit (pCtB) was evaluated as an
      intradermal genetic adjuvant for a model DNA vaccine expressing the human
      papillomavirus type 16 L1 capsid gene (p16L1) in mice. p16L1 was coadministered
      with plasmid pCtB or commercial polypeptide CtB as a positive control.
      Coadministration of pCtB induced a significant increment of specific anti-L1
      immunoglobulin A (IgA) antibodies in cervical secretions (P < 0.05) and fecal
      extracts (P < 0.005). Additionally, coadministration of pCtB enhanced the
      production of interleukin-2 and gamma interferon by spleen cells but did not
      affect the production of interleukin-4, suggesting a Th1-type helper response.
      Furthermore, improved CD8+ T-cell-mediated cytotoxic activity was observed in
      mice vaccinated with the DNA vaccine with pCtB as an adjuvant. This adjuvant
      effect was comparable to that induced by the CtB polypeptide. These results
      indicate that intradermal coadministration of pCtB is an adequate means to
      enhance the mucosa-, Th1-, and CD8(+)-mediated cytotoxic responses induced by a
      DNA vaccine.

PMID- 15242947
TI  - Delineation of the role of platelet-activating factor in the immunoglobulin G2
      antibody response.
AB  - Localized aggressive periodontitis (LAgP) is a chronic inflammatory disease
      characterized by severe destruction of periodontal tissues surrounding the first
      molars and incisors. LAgP subjects produce large amounts of immunoglobulin G2
      (IgG2) antibody against oral pathogens, and this response is inversely correlated
      with the severity of disease. We previously demonstrated that platelet-activating
      factor (PAF) is required for optimal IgG2 responses. The present investigation
      was designed to determine the mechanism of IgG2 induction by PAF. Exogenous PAF
      acetylhydrolase suppressed approximately 80% of pokeweed mitogen-stimulated IgG2
      production, confirming that PAF is essential for optimal responses. PAF-activated
      leukocytes produced gamma interferon (IFN-gamma), a Th1 cytokine that has been
      associated with IgG2 responses in previous studies. The monocyte-derived
      cytokines interleukin-12 (IL-12) and IL-18 are upstream of IFN-gamma production,
      and IgG2 production was suppressed by neutralizing antibodies against these
      proteins. In addition, PAF induced monocyte-derived dendritic cells (DC) but not
      macrophages (MPhi) to secrete IL-12 and IL-18. This observation was interesting
      because monocyte differentiation in LAgP subjects is skewed to the DC phenotype.
      Although other investigators have implicated IFN-gamma in IgG2 production, its
      precise role in this response is controversial. Our studies suggest that IFN
      gamma induces isotype switching to IgG2 but only in concert with the Th2 cytokine
      IL-4. Thus, it appears that the unique PAF metabolism of LAgP monocytes or DC
      promotes Th1 responses that are essential for optimal IgG2 antibody production.
      As IgG2 antibodies opsonize oral bacteria and promote their clearance and
      destruction, these alterations in PAF metabolism may be essential for limiting
      disease severity in LAgP patients.

PMID- 15242948
TI  - Use of recombinant ESAT-6:CFP-10 fusion protein for differentiation of infections
      of cattle by Mycobacterium bovis and by M. avium subsp. avium and M. avium subsp.
      paratuberculosis.
AB  - Immunological diagnosis of Mycobacterium bovis infection of cattle is often
      confounded by cross-reactive responses resulting from exposure to other
      mycobacterial species, especially Mycobacterium avium. Early secretory antigenic
      target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are dominant gamma
      interferon (IFN-gamma)-inducing antigens of tuberculous mycobacteria, and they
      are absent from many environmental nontuberculous mycobacteria. Because M. avium
      exposure is the primary confounding factor in the diagnosis of M. bovis-infected
      animals, in vitro responses to a recombinant ESAT-6:CFP-10 (rESAT-6:CFP-10)
      fusion protein by blood leukocytes from cattle naturally exposed to M. avium or
      experimentally challenged with Mycobacterium avium subsp. avium or Mycobacterium
      avium subsp. paratuberculosis were compared to responses by M. bovis-infected
      cattle. Responses to heterogeneous mycobacterial antigens (i.e., purified protein
      derivatives [PPDs] and whole-cell sonicates [WCSs]) were also evaluated. Tumor
      necrosis factor alpha (TNF-alpha), IFN-gamma, and nitric oxide responses by M.
      bovis-infected cattle to rESAT-6:CFP-10 exceeded (P < 0.05) the corresponding
      responses by cattle naturally sensitized to M. avium. Experimental infection with
      M. bovis, M. avium, or M. avium subsp. paratuberculosis induced significant (P <
      0.05) IFN-gamma and nitric oxide production to WCS and PPD antigens, regardless
      of the mycobacterial species used for the preparation of the antigen. Responses
      to homologous crude antigens generally exceeded responses to heterologous
      antigens. Nitric oxide and IFN-gamma responses to rESAT-6:CFP-10 by blood
      leukocytes from M. bovis-infected calves exceeded (P < 0.05) the corresponding
      responses of noninfected, M. avium-infected, and M. avium subsp. paratuberculosis
      infected calves. Despite the reported potential for secretion of immunogenic ESAT
      6 and CFP-10 proteins by M. avium and M. avium subsp. paratuberculosis, it
      appears that use of the rESAT-6:CFP-10 fusion protein will be useful for the
      detection of tuberculous cattle in herds with pre-existing sensitization to M.
      avium and/or M. avium subsp. paratuberculosis.

PMID- 15242949
TI  - Eucaryotic expression of the nucleocapsid protein gene of porcine circovirus type
      2 and use of the protein in an indirect immunofluorescence assay for serological
      diagnosis of postweaning multisystemic wasting syndrome in pigs.
AB  - The purpose of this study was to develop a sensitive, rapid, and inexpensive
      immunofluorescence assay (IFA) using a recombinant porcine circovirus type 2
      (PCV2) nucleocapsid protein for the serological detection of PCV2-specific
      antibodies in pig sera. The viral nucleocapsid protein encoded by the PCV2 ORF2
      gene has recently been identified as the most immunoreactive viral protein that
      carries type-specific antigenic determinants. The ORF2 sequence of the IAF-2897
      strain of PCV2 has been cloned into a pCEP5 eucaryotic expression vector under
      the control of the cytomegalovirus promoter, downstream of a polyhistidine
      sequence tag. The recombinant plasmid was used in transfection experiments with
      human epithelial kidney 293 cells that were further tested, and positive
      expression of the viral nucleocapsid protein was confirmed by IFA and Western
      blotting. Strong, specific fluorescence was observed in the nuclei of transfected
      cells. Test specificity to PCV2 was verified with several related infectious
      agents. Sensitivity was compared to that of standard IFA using PCV2-infected
      cells by evaluating the reactivities of 44 field serum samples from pigs on farms
      with a porcine population suffering from postweaning multisystemic wasting
      syndrome. The recombinant nucleocapsid-based test was able to detect 15 more
      positive-testing pigs than the PCV2-based IFA. Therefore, the relative
      sensitivity of the latter test was estimated at only 57.1% compared to that of
      the recombinant nucleocapsid-based test. The recombinant fusion protein has been
      purified by affinity chromatography and is being used to develop further
      sensitive serological tests.

PMID- 15242951
TI  - Use of bispecific antibodies in molecular velcro assays whose specificity
      approaches the theoretical limit of immunodetection for Bordetella pertussis.
AB  - A bispecific monoclonal antibody (bsMAb) that detects Bordetella pertussis, the
      causative agent of whooping cough, and horseradish peroxidase (HRPO) has been
      developed by use of the quadroma technology. A quadroma, P123, was produced by
      fusing two well-characterized hybridomas against the bacterium and the enzyme and
      was subcloned to obtain a stable bsMAb-secreting cell line. The quadroma was
      theoretically expected to produce up to 10 different molecular species of
      immunoglobulins, so secreted bispecific antibody was complexed with excess HRPO
      and the HRPO-bsMAb complex was purified in one step by benzhydroxamic acid
      agarose affinity cochromatography. An ultrasensitive homosandwich molecular
      "velcro" enzyme-linked immunosorbent assay for the detection of B. pertussis
      whole bacteria with HRPO-bsMAb was established in both microplate and
      nasopharyngeal swab formats. This assay demonstrates a high sensitivity that
      approaches the theoretical limit of detection of one bacterium. This new
      nanoprobe can be used to develop a new generation of assays that are simple,
      inexpensive alternatives to quantitative PCR and that can be used by clinical
      laboratories. This strategy of homosandwich assays with solid-phase monospecific
      antibodies and solution-phase bsMAb with specificity for the same repeating
      surface determinants can be applied to generate ultrasensitive immunodiagnostic
      assays for viruses and bacteria.

PMID- 15242950
TI  - Bacterial clearance and cytokine profiles in a murine model of postsurgical
      nosocomial pneumonia.
AB  - The development of a nosocomial pneumonia is facilitated by alterations in host
      innate pulmonary antibacterial defenses following surgical trauma, which can
      result in decreased pulmonary bacterial clearance and increased morbidity and
      mortality. In a murine model of postoperative nosocomial infection, surgical
      stress (laparotomy) decreased Escherichia coli clearance from the lungs of
      animals that underwent surgery. Consistent with previous studies, (i) pulmonary
      levels of tumor necrosis factor alpha at 6 h and of interleukin-1beta (IL-1beta),
      IL-6, and gamma interferon (IFN-gamma) at 24 h post-bacterial infection (PBI)
      were decreased in animals that underwent laparotomy 24 h prior to E. coli
      infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC
      and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli
      animals compared to E. coli-only animals; however, at 24 h PBI, levels were
      higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant
      protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group;
      (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total
      number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was
      decreased in comparison to that in E. coli-only animals, resulting in decreased
      bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI.
      Similar changes in cytokine profiles, pulmonary bacterial clearance, and
      mortality were consistent with reported findings in patients following surgical
      trauma. This model, therefore, provides a clinically relevant system in which the
      molecular and cellular mechanisms that lead to the development of nosocomial
      pneumonia can be further explored.

PMID- 15242952
TI  - Evolution of vaccinia virus-specific CD8+ cytotoxic T-lymphocyte responses in
      primary vaccinees and revaccinees.
AB  - Determination of successful vaccination with vaccinia virus is based on visual
      confirmation of a dermal response (take). Some revaccinees do not manifest a
      take, which may be due to a preexisting immunity rather than to poor technique or
      inadequate virus. Cytotoxic T-lymphocyte (CTL) response appears to be the most
      important immune defense in limiting response to vaccination. We evaluated
      vaccinia virus-specific CTL responses in revaccinees. Subjects with and without
      takes displayed comparable CTL responses. Vaccinia virus-specific CD8+ CTL
      responses may be useful in interpreting the response to vaccination, particularly
      in individuals who are revaccinated and have difficult-to-interpret visual takes.

PMID- 15242953
TI  - Evaluation of recombinant antigen-based assays for diagnosis of bullous
      autoimmune diseases.
AB  - The diagnosis of autoimmune bullous diseases is based on clinical observation and
      on the presence of autoantibodies directed to molecules involved in the adhesion
      systems of the skin. Immunofluorescence assays are the currently accepted method
      for detection of autoantibodies; such assays depend greatly on the skill of
      operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1),
      Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous
      pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA)
      for the detection of specific antibodies. The present study was undertaken to
      evaluate the sensitivity and specificity of these immunoassays and to determine
      the correlation between the results and the clinical aspects of diseases. Serum
      samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous
      pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from
      patients with unrelated autoimmune conditions were tested. Anti-desmoglein
      reactivity was detected in all the patients with pemphigus and in none of the
      controls. Patients with the more benign form of cutaneous disease had anti-Dsg1
      antibodies, while patients with deeper cutaneous lesions or with mucosal
      involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay
      was positive for 66.6% of patients with bullous pemphigoid and for none of the
      patients with mucous membrane pemphigoid, and no reactivity was detected in the
      control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the
      diagnosis of pemphigus and provide information on the clinical phenotype of the
      disease. However, the sensitivity of EIA for detection of autoantibodies in
      bullous pemphigoid should be improved by the use of additional antigens or
      epitopes.

PMID- 15242954
TI  - Novel hairpin-shaped primer assay to study the association of the -44 single
      nucleotide polymorphism of the DEFB1 gene with early-onset periodontal disease.
AB  - A powerful, cost-effective new method for studying single-nucleotide
      polymorphisms (SNPs) is described. This method is based on the use of hairpin
      shaped primers (HP), which give a sensitive and specific PCR amplification of
      each specific allele, without the use of costly fluorophore-labeled probes and
      any post-PCR manipulation. The amplification is monitored in real-time using SYBR
      Green I dye and takes only 2 h to yield results. The HP assay has a simple design
      and utilizes a conventional real-time PCR apparatus. The -44 C-->G transversion
      in the DEFB1 gene (which encodes human beta-defensin 1) has been previously
      associated with Candida carriage in oral epithelia. In this study, we analyzed
      the association between early-onset periodontal disease (EOP) and the -44 SNP. We
      used an HP assay to study the distribution of the -44 SNP in 264 human DNAs
      obtained from two cohorts of EOP patients and healthy controls from different
      ethnic backgrounds. The results indicate that the -44 SNP has a similar
      distribution between EOP and healthy patients, suggesting that it is not
      associated with the disease.

PMID- 15242955
TI  - HLA class II profile and distribution of HLA-DRB1 and HLA-DQB1 alleles and
      haplotypes among Lebanese and Bahraini Arabs.
AB  - The gene frequencies of HLA class II alleles were studied in 95 healthy Lebanese
      Arab and 72 healthy Bahraini Arab subjects. Our aim was to establish the genetic
      relationship between Bahraini and Lebanese Arabs in terms of HLA class II gene
      and haplotype frequencies and to compare these results with frequencies for other
      countries with populations of Caucasian and non-Caucasian descent. Subjects were
      unrelated and of both sexes, and HLA-DRB1 and -DQB1 genotyping was done by the
      PCR sequence-specific primer technique. Comparative analysis of the HLA-DR and 
      DQ alleles revealed differences in the allelic distribution among Bahraini and
      Lebanese subjects. Analysis of the 25 HLA-DRB1 alleles that have been
      investigated showed that the DRB1*040101 and DRB1*110101 alleles were more
      frequent among Lebanese, whereas DRB1*030101 and DRB1*160101 alleles were more
      frequent among Bahrainis. Similarly, of the seven HLA-DQB1 alleles analyzed, the
      presence of DQB1*0201 was more frequent among Bahrainis, whereas DQB1*030101 was
      more frequent among Lebanese. The DRB1*160101-DQB1*050101 (0.1318 versus 0.0379%)
      and DRB1*030101-DQB1*0201 (0.1202 versus 0.0321%) haplotypes were more frequent
      among Bahrainis, while the DRB1*110101-DQB1*030101 (0.3142 versus 0.1198%) and
      DRB1*040101-DQB1*0302 (0.1416 versus 0.0278%) haplotypes were more frequent in
      Lebanese subjects. Furthermore, a high prevalence of the DRB1*040101-DRB1*110101
      DQB1*0302-DQB1*030101 (12.63 versus 1.35%, P = 0.015) and the homozygous
      DRB1*110101-DRB1*110101-DQB1*030101-DQB1*030101 (7.37 versus 0.00%, P = 0.046)
      genotypes was seen among Lebanese, and DRB1*070101-DRB1*160101-DQB1*0201
      DQB1*050101 (6.76 versus 0.00%, P = 0.034) was seen more frequently among
      Bahraini subjects. Our results underline significant differences between these
      two populations in HLA class II distribution, provide basic information for
      further studies of major histocompatibility complex heterogeneity among Arabic
      speaking countries, and serve as a reference for further anthropological studies.

PMID- 15242956
TI  - Use of a novel enzyme immunoassay based on detection of circulating antigen in
      serum for diagnosis of Helicobacter pylori infection.
AB  - Recently, noninvasive diagnostic tests for Helicobacter pylori infection have
      gained in significance. We have developed a sensitive and specific noninvasive
      immunoassay based on the detection of an H. pylori circulating antigen (HpCA) in
      sera from H. pylori-infected individuals. Monospecific antibody and Western blot
      analyses were used to demonstrate the presence of the target antigen in H. pylori
      cell lysate and serum samples. A novel enzyme-linked immunosorbent assay (ELISA)
      was developed for the detection of HpCA in serum. Endoscopic biopsy specimens
      from the gastric antra of 221 individuals (143 males and 78 females) with
      dyspeptic symptoms were evaluated for H. pylori infection, with culture used as a
      "gold standard" for diagnosis. The target H. pylori antigen was identified at 58
      kDa. HpCA has been detected by ELISA with high degrees of sensitivity,
      specificity, and efficiency (>90%), and ELISA results show no significant
      difference (P > 0.05) from results of H. pylori culture of gastric biopsy
      specimens. The test's positive and negative predictive values were also high (95
      and 86%, respectively). In conclusion, a sensitive and specific immunoassay was
      developed for the detection of HpCA in human serum. This test can be applied for
      noninvasive laboratory and field diagnoses of H. pylori infection.

PMID- 15242958
TI  - Comparison of immunofluorescence, Western blotting, and cross-adsorption assays
      for diagnosis of African tick bite fever.
AB  - In testing paired serum samples from 40 consecutive cases of African tick bite
      fever, we detected diagnostic antibodies against spotted fever group rickettsiae
      in 45% of the patients by immunofluorescence assay (IFA) and in 100% of the
      patients by Western blotting (WB) (P < 0.01). A specific diagnosis of Rickettsia
      africae infection could be established in 15% of the patients by IFA and in 73%
      of the patients by a combination of WB and cross-adsorption assays (P < 0.01).

PMID- 15242957
TI  - Effect of pregnancy and human immunodeficiency virus infection on intracellular
      interleukin-2 production patterns.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection decreases the production of
      interleukin-2 (IL-2) from CD4+ and CD8+ T cells. Recombinant IL-2 (rIl-2) has
      been given to HIV-infected individuals to generate significant increases in CD4+
      T-cell counts. There are limited data regarding the effects of pregnancy and HIV
      infection on IL-2 production in humans. To investigate the effects of human
      pregnancy, HIV infection, and HIV therapy on IL-2 production, we evaluated 61
      women. Intracellular IL-2 production by CD4+ T cells from nonpregnant HIV
      infected women was significantly lower than in that in uninfected women (45% +/-
      8% versus 52% +/- 8%, P = 0.04). In contrast, there was no difference in levels
      of intracellular IL-2 production between HIV-infected and uninfected pregnant
      women. These observations suggest that pregnancy may down-regulate IL-2
      production regardless of HIV infection status. Future studies should evaluate IL
      2 production patterns in larger cohorts of women so that the physiological
      significance of IL-2 down-regulation in pregnancy can be further evaluated. This
      information is essential to assess the possible use of IL-2 supplementation
      therapy as a means of enhancing immune responses among HIV-infected pregnant
      women.

PMID- 15242959
TI  - Impact of serological methodology on assessment of the link between Chlamydia
      pneumoniae and vascular diseases.
AB  - We assessed the impact of five serologic tests on the link between Chlamydia
      pneumoniae and abdominal aortic aneurysms (AAA). The results of the tests were
      inconsistent. Agreement among the five tests was generally poor. Detection of the
      link between C. pneumoniae and AAA depends on the serologic methodology chosen.

PMID- 15242960
TI  - Kinetics of severe acute respiratory syndrome (SARS) coronavirus-specific
      antibodies in 271 laboratory-confirmed cases of SARS.
AB  - The sensitivities and specificities of an immunofluorescence assay and an enzyme
      immunoassay for detection of antibodies specific for severe acute respiratory
      syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS
      cases. The appearance and persistence of SARS-CoV-specific antibodies were
      assessed, with immunoglobulin G detected in 59% of samples collected within 14
      days and persisting for 60 to 95 days after the onset of illness.

PMID- 15242961
TI  - Identification and phenotyping of leukocytes in bovine bronchoalveolar lavage
      fluid.
AB  - A method is proposed to identify leukocyte subpopulations in bovine
      bronchoalveolar lavage fluid by dual-laser flow cytometry. The technique uses
      several parameters, i.e., exclusion of highly autofluorescent alveolar
      macrophages and inclusion of leukocytes on the basis of labeling by specific
      antibodies and light scatter characteristics.

PMID- 15242962
TI  - Evaluation of a monoclonal antibody-based test for detection of Helicobacter
      pylori-specific antigen in stool samples from mice.
AB  - A test using monoclonal antibodies for detection of antigen in stool samples was
      compared with culture and histology for noninfected (n = 25), Helicobacter pylori
      infected (n = 25), and Helicobacter felis-infected (n = 6) mice. Sensitivity and
      specificity were 96%. The monoclonal antibody-based test is therefore a
      noninvasive technique that is able to diagnose H. pylori infection in mice.

PMID- 15242963
TI  - Clinical evaluation of a chemiluminescence immunoassay for determination of
      immunoglobulin g avidity to human cytomegalovirus.
AB  - Clinical evaluation of a novel fully automated chemiluminescence immunoassay for
      determination of immunoglobulin G avidity to human cytomegalovirus (HCMV) showed
      92.8% sensitivity and 84.7% specificity in detecting a recent (< or =90 days)
      primary HCMV infection. The assay appears useful for accurately diagnosing recent
      primary HCMV infections.

PMID- 15242964
TI  - Association between familial deficiency of mannose-binding lectin and mutations
      in the corresponding gene and promoter region.
AB  - In a recent report, our group presented clinical research data supporting the
      role of mannose-binding lectin (MBL) deficiency in susceptibility to
      meningococcal disease (W. A. Bax, O. J. J. Cluysenaer, A. K. M. Bartelink, P. C.
      Aerts, R. A. B. Ezekowitz, and H. van Dijk, Lancet 354:1094-1095, 1999). This
      association was reported earlier by Hibberd et al. (M. L. Hibberd, M. Sumiya, J.
      A. Summerfield, R. Booy, M. Levin, and the Meningococcal Research Group, Lancet
      353:1049-1053, 1999) but was not based on family data. Our study included three
      members of one family who had acquired meningococcal meningitis in early
      adulthood. The objective of the present study was to investigate whether the
      genotypes of the MBL gene in this family, analyzed by PCR, correlate with MBL
      concentrations. We found that genotype variants in the MBL gene and promoter
      region match the low functional MBL levels (<0.25 microg of equivalents/ml) in
      the sera of the three patients in this family and that a significant correlation
      between genotype MBL deficiency and meningococcal disease existed.

PMID- 15242965
TI  - Long-term effects of immunization with recombinant lipoprotein outer surface
      protein a on serologic test for lyme disease.
AB  - Immunization with recombinant lipoprotein outer surface protein A vaccine is
      known to interfere with some serologic tests for Lyme disease. We tested sera
      from 152 vaccine recipients by using in-house and commercial Western blot assays
      and found that vaccination caused interference in up to 25% of recipients and can
      persist for over 6 years.

PMID- 15242966
TI  - Normal values for CD4 and CD8 lymphocyte subsets in healthy Chinese adults from
      Shanghai.
AB  - The aim of this study was to establish reference ranges for lymphocyte subsets in
      Chinese adults. Venous blood specimens were obtained from 614 healthy, human
      immunodeficiency virus (HIV)-seronegative adults in Shanghai. Flow cytometry was
      used to determine percentages and absolute numbers of CD4 and CD8 T lymphocytes.
      Mean values for CD4 and CD8 lymphocytes were 727 and 540 cells/microl,
      respectively, yielding a CD4/CD8 ratio of 1.49. While CD8 lymphocyte values
      varied with age and gender, no significant differences in CD4 lymphocyte values
      were observed. Shanghai adults had approximately 100 fewer CD4 lymphocytes/microl
      on average than Caucasians, suggesting that lower CD4 lymphocyte cutoffs for
      classifying and monitoring HIV infection may be needed in China.

PMID- 15242967
TI  - Evaluation of Clonorchis sinensis recombinant 7-kilodalton antigen for
      serodiagnosis of clonorchiasis.
AB  - The diagnostic applicability of the Clonorchis sinensis recombinant 7-kDa protein
      was evaluated. In enzyme-linked immunosorbent assays and immunoblots, the protein
      showed high sensitivities (81.3 and 71.9%, respectively) and specificities (92.6
      and 89.7%, respectively) for sera obtained from various helminthic infections.
      Some paragonimiasis sera showed cross-reactions. The antigen might be valuable in
      the serodiagnosis of human clonorchiasis.

PMID- 15242968
TI  - Transcriptional regulation of cardiac progenitor cell populations.
AB  - Transcriptome-wide analysis of dynamically regulated progenitor cell populations
      has the potential to elucidate key aspects of cardiac development. The heart, as
      the first organ to develop in the mammal, is a technically challenging but
      clinically relevant target for study. To define the transcriptional program of
      the cardiac progenitor, we used a novel transgenic strategy and fluorescence
      activated cell sorting to reliably label and isolate cardiac progenitors directly
      from mouse embryos. Pure populations of cardiac progenitor cells were isolated
      from the cardiac crescent and 2 subsequent stages of heart development: the
      linear heart tube and the looping heart. RNA was isolated from stage-specific
      cardiac progenitors and subjected to transcriptome analysis by oligonucleotide
      array hybridization. The cardiac transcriptional regulatory programs were
      compared with the molecular programs of age-matched noncardiac embryonic cells,
      embryonic stem cells, adult cardiomyocytes, and each other to identify sets of
      genes exhibiting differential expression in the cardiac progenitor cell
      population. These results define the transcriptional profile of mammalian cardiac
      progenitor cells and provide insight into the molecular regulation of the
      earliest periods of heart development.

PMID- 15242969
TI  - Subcortical Ca2+ waves sneaking under the plasma membrane in endothelial cells.
AB  - Subplasmalemmal Ca2+, dynamically equilibrated with extracellular Ca2+, affects
      numerous signaling molecules, effectors, and events within this restricted space.
      We demonstrated the presence of a novel Ca2+ wave propagating beneath the plasma
      membrane in response to acute elevation of extracellular [Ca2+], by targeting a
      Ca2+ sensor, cameleon, to the endothelial plasmalemma. These subcortical waves,
      spatially distinct from classical cytosolic Ca2+ waves, originated in localized
      regions and propagated throughout the subplasmalemma. Translocation of an
      expressed GFP fused with a PH domain of PLC from the plasma membrane to the
      cytosol accompanied these subcortical waves, and U73122 attenuated not only the
      GFP-PH translocation, but also the peak amplitude of the subcortical Ca2+ waves;
      this finding suggests the involvement of local IP3 production through PLC
      mediated PIP2 hydrolysis in the initiation of these waves. Changes in NO
      production as well as PKCbeta-GFP translocation from the cytosol to the plasma
      membrane, but not of GFP-PLA2 to perinuclear endomembranes, were associated with
      the subplasmalemmal Ca2+ changes. Thus, extracellular Ca2+ maintains the basal
      PLC activity of the plasma membrane, is involved in the initiation of
      compartmentalized subcortical Ca2+ waves, and regulates Ca2+-dependent signaling
      molecules residing in or translocated to the plasma membrane. The full text of
      this article is available online at http://circres.ahajournals.org.

PMID- 15242970
TI  - Creation of a genetic calcium channel blocker by targeted gem gene transfer in
      the heart.
AB  - Calcium channel blockers are among the most commonly used therapeutic drugs.
      Nevertheless, the utility of calcium channel blockers for heart disease is
      limited because of the potent vasodilatory effect that causes hypotension, and
      other side effects attributable to blockade of noncardiac channels. Therefore,
      focal calcium channel blockade by gene transfer is highly desirable. With a view
      to creating a focally applicable genetic calcium channel blocker, we
      overexpressed the ras-related small G-protein Gem in the heart by somatic gene
      transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium
      current density in ventricular myocytes, resulting in the abbreviation of action
      potential duration. Furthermore, transduction of Gem resulted in a significant
      shortening of the electrocardiographic QTc interval and reduction of left
      ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV)
      node significantly slowed AV nodal conduction (prolongation of PR and AH
      intervals), which was effective in the reduction of heart rate during atrial
      fibrillation. Thus, these results indicate that gene transfer of Gem functions as
      a genetic calcium channel blocker, the local application of which can effectively
      modulate cardiac electrical and contractile function.

PMID- 15242972
TI  - Postconditioning: a form of "modified reperfusion" protects the myocardium by
      activating the phosphatidylinositol 3-kinase-Akt pathway.
AB  - Brief intermittent episodes of ischemia and reperfusion, at the onset of
      reperfusion after a prolonged period of ischemia, confer cardioprotection, a
      phenomenon termed "ischemic postconditioning" (Postcond). We hypothesized that
      this phenomenon may just represent a modified form of reperfusion that activates
      the reperfusion injury salvage kinase (RISK) pathway. Isolated perfused rat
      hearts were subjected to: (a) 35 minutes of ischemia and 120 minutes of
      reperfusion, and infarct size was determined by tetrazolium staining; or (b) 35
      minutes of ischemia and 7 minutes of reperfusion, and the phosphorylation states
      of Akt, endothelial NO synthase (eNOS), and p70S6K were determined. Postcond
      reduced infarct size from 51.2+/-3.4% to 31.5+/-4.1% (P<0.01), an effect
      comparable with ischemic preconditioning (IPC; 27.5+/-2.3%; P<0.01). Of interest,
      the combined protective effects of IPC and Postcond were not additive (30.1+/
      4.8% with IPC+Postcond; P=NS). Inhibiting phosphatidylinositol 3-kinase (PI3K) at
      reperfusion using LY or Wortmannin (Wort) during the first 15 minutes of
      reperfusion completely abolished Postcond-induced protection (31.5+/-4.1% with
      Postcond versus 51.7+/-4.5% with Postcond+LY, P<0.01; 56.2+/-10.1% with Postcond+
      Wort; P<0.01), suggesting that Postcond protects the heart by activating PI3K
      Akt. Western blot analysis demonstrated that Postcond induced a significant
      increase in phosphorylation of Akt, eNOS, and p70S6K in an LY- and Wort-sensitive
      manner. In conclusion, we show for the first time that ischemic Postcond protects
      the myocardium by activating the prosurvival kinases PI3K-Akt, eNOS, and p70S6K
      in accordance with the RISK pathway.

PMID- 15242971
TI  - Program of cell survival underlying human and experimental hibernating
      myocardium.
AB  - Hibernating myocardium refers to chronically dysfunctional myocardium in patients
      with coronary artery disease in which cardiac viability is maintained and whose
      function improves after coronary revascularization. It is our hypothesis that
      long-term adaptive genomic mechanisms subtend the survival capacity of this
      ischemic myocardium. Therefore, the goal of this study was to determine whether
      chronic repetitive ischemia elicits a gene program of survival protecting
      hibernating myocardium against cell death. Accordingly, we measured the
      expression of survival genes in hibernating myocardium, both in patients
      surgically treated for hibernation and in a chronic swine model of repetitive
      ischemia reproducing the features of hibernation. Human hibernating myocardium
      was characterized by an upregulation of genes and corresponding proteins involved
      in anti-apoptosis (IAP), growth (VEGF, H11 kinase), and cytoprotection (HSP70,
      HIF-1alpha, GLUT1). In the swine model, the same genes and proteins were
      upregulated after repetitive ischemia, which was accompanied by a concomitant
      decrease in myocyte apoptosis. These changes characterize viable tissue, because
      they were not found in irreversibly injured myocardium. Our report demonstrates a
      novel mechanism by which the activation of an endogenous gene program of cell
      survival underlies the sustained viability of the hibernating heart. Potentially,
      promoting such a program offers a novel opportunity to salvage postmitotic
      tissues in conditions of ischemia.

PMID- 15242973
TI  - Regulation of vascular L-type Ca2+ channels by phosphatidylinositol 3,4,5
      trisphosphate.
AB  - Modulation of voltage-gated L-type Ca2+ channels by phosphoinositide 3-kinase
      (PI3K) regulates Ca2+ entry and plays a crucial role in vascular excitation
      contraction coupling. Angiotensin II (Ang II) activates Ca2+ entry by stimulating
      L-type Ca2+ channels through Gbeta-sensitive PI3K in portal vein myocytes.
      Moreover, PI3K and Ca2+ entry activation have been reported to be necessary for
      receptor tyrosine kinase-coupled and G protein-coupled receptor-induced DNA
      synthesis in vascular cells. We have previously shown that tyrosine kinase
      regulated class Ia and G protein-regulated class Ib PI3Ks are able to modulate
      vascular L-type Ca2+ channels. PI3Ks display 2 enzymatic activities: a lipid
      kinase activity leading to the formation of phosphatidylinositol 3,4,5
      trisphosphate [PI(3,4,5)P3 or PIP3] and a serine-kinase activity. Here we show
      that exogenous PIP3 applied into the cell through the patch pipette is able to
      reproduce the Ca2+ channel-stimulating effect of Ang II and PI3Ks. Moreover, the
      Ang II-induced PI3K-mediated stimulation of Ca2+ channel and the resulting
      increase in cytosolic Ca2+ concentration are blocked by the anti-PIP3 antibody.
      Mutants of PI3K transfected into vascular myocytes also revealed the essential
      role of the lipid-kinase activity of PI3K in Ang II-induced Ca2+ responses. These
      results suggest that PIP3 is necessary and sufficient to activate a Ca2+ influx
      in vascular myocytes stimulated by Ang II.

PMID- 15242974
TI  - Angiogenic effects of adrenomedullin in ischemia and tumor growth.
AB  - Adrenomedullin (AM) is a novel vasodilating peptide involved in the regulation of
      circulatory homeostasis and implicated in the pathophysiology of cardiovascular
      disease. We tested the hypothesis that AM also possesses angiogenic properties.
      Using laser Doppler perfusion imaging, we found that AM stimulated recovery of
      blood flow to the affected limb in the mouse hind-limb ischemia model. AM exerted
      this effect in part by promoting expression of vascular endothelial growth factor
      (VEGF) in the ischemic limb, and immunostaining for CD31 showed the enhanced flow
      to reflect increased collateral capillary density. By enhancing tumor
      angiogenesis, AM also promoted the growth of subcutaneously transplanted sarcoma
      180 tumor cells. However, heterozygotic AM knockout mice (AM+/-) showed
      significantly less blood flow recovery with less collateral capillary development
      and VEGF expression than their wild-type littermates. Similarly, mice treated
      with AM22-52, a competitive inhibitor of AM, showed reduced capillary
      development, and growth of sarcoma 180 tumors was inhibited in AM+/- and AM22-52
      treated mice. Notably, administration of VEGF or AM rescued blood flow recovery
      and capillary formation in AM+/- and AM22-52-treated mice. In cocultures of
      endothelial cells and fibroblasts, AM enhanced VEGF-induced capillary formation,
      whereas in cultures of endothelial cells AM enhanced VEGF-induced Akt activation.
      These results show that AM possesses novel angiogenic properties mediated by its
      ability to enhance VEGF expression and Akt activity. This may make AM a useful
      therapeutic tool for relieving ischemia; conversely, inhibitors of AM could be
      useful for clinical management of tumor growth.

PMID- 15242975
TI  - Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on
      cross-talk between the PI3K and MAPK signaling pathways.
AB  - Atheroma formation involves the movement of vascular smooth muscle cells (VSMC)
      into the subendothelial space. The aim of this study was to determine the
      involvement of PI3K and MAPK pathways and the importance of cross-talk between
      these pathways, in glucose-potentiated VSMC chemotaxis to serum factors. VSMC
      chemotaxis occurred in a serum gradient in 25 mmol/L glucose (but not in 5 mmol/L
      glucose) in association with increased phosphorylation (activation) of Akt and
      ERK1/2 in PI3K and MAPK pathways, respectively. Inhibitors of these pathways
      blocked chemotaxis, as did an mTOR inhibitor. VSMC expressed all class IA PI3K
      isoforms, but microinjection experiments demonstrated that only the p110beta
      isoform was involved in chemotaxis. ERK1/2 phosphorylation was reduced not only
      by MAPK pathway inhibitors but also by PI3K and mTOR inhibitors; when PI3K was
      inhibited, ERK phosphorylation could be induced by microinjected activated Akt,
      indicating important cross-talk between the PI3K and ERK1/2 pathways. Glucose
      potentiated phosphorylation of molecules in the p38 and JNK MAPK pathways
      inhibited these pathways but did not affect chemotaxis. The statin, mevinolin,
      blocked chemotaxis through its effects on the MAPK pathway. Mevinolin-inhibited
      chemotaxis was restored by farnesylpyrophosphate but not by
      geranylgeranylpyrophosphate; in the absence of mevinolin, inhibition of
      farnesyltransferase reduced ERK phosphorylation and blocked chemotaxis,
      indicating a role for the Ras family of GTPases (MAPK pathway) under these
      conditions. In conclusion, glucose sensitizes VSMC to serum, inducing chemotaxis
      via pathways involving p110beta-PI3K, Akt, mTOR, and ERK1/2 MAPK. Cross-talk
      between the PI3K and MAPK pathways is necessary for VSMC chemotaxis under these
      conditions.

PMID- 15242976
TI  - Protein kinase Cepsilon overexpression alters myofilament properties and
      composition during the progression of heart failure.
AB  - We report characterization of a transgenic mouse that overexpresses
      constitutively active protein kinase Cepsilon in the heart and slowly develops a
      dilated cardiomyopathy with failure. The hemodynamic, mechanical, and biochemical
      properties of these hearts demonstrate a series of temporal events that mark the
      progression of the disease. In the 3-month transgenic (TG) animals, contractile
      properties and gene expression measurements are normal, but an increase in
      myofibrillar Ca2+ sensitivity and thin filament protein phosphorylation is noted.
      At 6 months, there is a decrease in the myofibrillar Ca2+ sensitivity, a
      significant increase in beta-myosin heavy chain mRNA and protein, normal cardiac
      function, but a blunted response to an inotropic challenge. The transition at 9
      months is especially interesting because age-related changes appear to contribute
      to the decline in function seen in the TG heart. At this point, there is a
      decline in baseline function and maximum tension produced by the myofibrils,
      which is coincident with the onset of atrial myosin light chain isoform re
      expression in the ventricles. In the 12-month TG mice, there is clear hemodynamic
      and geometric evidence of failure. Alterations in the composition of the
      myofibrils persist but the phosphorylation of myosin light chain 2v is
      dramatically different at this age compared with all others. We interpret these
      data to implicate the disruption of the myofibrillar proteins and their
      interactions in the propagation of dilated cardiac disease.

PMID- 15242977
TI  - Thromboxane A2 receptor signaling inhibits vascular endothelial growth factor
      induced endothelial cell differentiation and migration.
AB  - Vascular endothelial growth factor (VEGF) is an important patho-physiological
      mediator of angiogenesis. VEGF-induced endothelial cell (EC) migration and
      angiogenesis often occur in complicated environments containing multiple agents
      capable of modifying the response. Thromboxane (TX) A2 is released from multiple
      cell types and is a prime mediator of pathogenesis of many vascular diseases.
      Human EC express both TXA2 receptor (TP) isoforms; however, the effects of
      individual TP isoforms on VEGF-induced EC migration and angogenesis are unknown.
      We report here that the TXA2 mimetic [1S-(1alpha, 2beta(5Z), 3alpha(1E, 3R),
      4alpha]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxab icyclo-[2.2.1]heptan
      2yl]-5'-heptenoic acid (IBOP) (100 nmol/L) is a potent antagonist (IC50 30
      nmol/L) of VEGF-induced EC migration and differentiation. TPbeta, but not
      TPalpha, expression is required for the inhibition of VEGF-induced migration and
      angiogenesis. IBOP costimulation suppressed nitric oxide (NO) release from VEGF
      treated EC through decreased activation of Akt, eNOS, and PDK1. TPbeta
      costimulation also ablated the increase in focal adhesion formation in response
      to VEGF. This mechanism was characterized by decreased recruitment of focal
      adhesion kinase (FAK) and vinculin to the alpha(v)beta3 integrin and reduced FAK
      and Src activation in response to VEGF. Addition of NO donors together with
      transfection of a constitutively active Src construct could circumvent the
      blockade of VEGF-induced migration by TP; however, neither intervention alone was
      sufficient. Thus, TP stimulation appears to limit angiogenesis, at least in part,
      by inhibiting the pro-angiogenic cytokine VEGF. These data further support a role
      for antagonism of TP activation in enhancing the angiogenic response in tissues
      exposed to elevated TXA2 levels in which revascularization is important.

PMID- 15242978
TI  - Role of itraconazole metabolites in CYP3A4 inhibition.
AB  - Itraconazole (ITZ) is a potent inhibitor of CYP3A in vivo. However, unbound
      plasma concentrations of ITZ are much lower than its reported in vitro Ki, and no
      clinically significant interactions would be expected based on a reversible
      mechanism of inhibition. The purpose of this study was to evaluate the reasons
      for the in vitro-in vivo discrepancy. The metabolism of ITZ by CYP3A4 was
      studied. Three metabolites were detected: hydroxy-itraconazole (OH-ITZ), a known
      in vivo metabolite of ITZ, and two new metabolites: keto-itraconazole (keto-ITZ)
      and N-desalkyl-itraconazole (ND-ITZ). OHITZ and keto-ITZ were also substrates of
      CYP3A4. Using a substrate depletion kinetic approach for parameter determination,
      ITZ exhibited an unbound K(m) of 3.9 nM and an intrinsic clearance (CLint) of
      69.3 ml.min(-1).nmol CYP3A4(-1). The respective unbound Km values for OH-ITZ and
      keto-ITZ were 27 nM and 1.4 nM and the CLint values were 19.8 and 62.5 ml.min(
      1).nmol CYP3A4(-1). Inhibition of CYP3A4 by ITZ, OH-ITZ, keto-ITZ, and ND-ITZ was
      evaluated using hydroxylation of midazolam as a probe reaction. Both ITZ and OH
      ITZ were competitive inhibitors of CYP3A4, with unbound Ki (1.3 nM for ITZ and
      14.4 nM for OH-ITZ) close to their respective Km. ITZ, OH-ITZ, keto-ITZ and ND
      ITZ exhibited unbound IC50 values of 6.1 nM, 4.6 nM, 7.0 nM, and 0.4 nM,
      respectively, when coincubated with human liver microsomes and midazolam
      (substrate concentration < Km). These findings demonstrate that ITZ metabolites
      are as potent as or more potent CYP3A4 inhibitors than ITZ itself, and thus may
      contribute to the inhibition of CYP3A4 observed in vivo after ITZ dosing.

PMID- 15242979
TI  - Frayed nerves in myocardial infarction: the importance of rewiring.

PMID- 15242980
TI  - Plasticity of myocytes and capillaries: a possible coordinating role for VEGF.

PMID- 15242981
TI  - Mesenchymal stem cells and their potential as cardiac therapeutics.
AB  - Mesenchymal stem cells (MSCs) represent a stem cell population present in adult
      tissues that can be isolated, expanded in culture, and characterized in vitro and
      in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes,
      and they can support hematopoietic stem cells or embryonic stem cells in culture.
      Evidence suggests MSCs can also express phenotypic characteristics of
      endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte
      cells. When introduced into the infarcted heart, MSCs prevent deleterious
      remodeling and improve recovery, although further understanding of MSC
      differentiation in the cardiac scar tissue is still needed. MSCs have been
      injected directly into the infarct, or they have been administered intravenously
      and seen to home to the site of injury. Examination of the interaction of
      allogeneic MSCs with cells of the immune system indicates little rejection by T
      cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the
      shelf" therapeutic use for multiple recipients. Clinical use of cultured human
      MSCs (hMSCs) has begun for cancer patients, and recipients have received
      autologous or allogeneic MSCs. Research continues to support the desirable traits
      of MSCs for development of cellular therapeutics for many tissues, including the
      cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide
      an excellent model for development of stem cell therapeutics, and their potential
      use in the cardiovascular system is currently under investigation in the
      laboratory and clinical settings.

PMID- 15242982
TI  - Optical imaging of the heart.
AB  - Optical techniques have revolutionized the investigation of cardiac cellular
      physiology and advanced our understanding of basic mechanisms of electrical
      activity, calcium homeostasis, and metabolism. Although optical methods are
      widely accepted and have been at the forefront of scientific discoveries, they
      have been primarily applied at cellular and subcellular levels and considerably
      less to whole heart organ physiology. Numerous technical difficulties had to be
      overcome to dynamically map physiological processes in intact hearts by optical
      methods. Problems of contraction artifacts, cellular heterogeneities, spatial and
      temporal resolution, limitations of surface images, depth-of-field, and need for
      large fields of view (ranging from 2x2 mm2 to 3x3 cm2) have all led to the
      development of new devices and optical probes to monitor physiological parameters
      in intact hearts. This review aims to provide a critical overview of current
      approaches, their contributions to the field of cardiac electrophysiology, and
      future directions of various optical imaging modalities as applied to cardiac
      physiology at organ and tissue levels.

PMID- 15242983
TI  - Lipids from oxidized low-density lipoprotein modulate human trophoblast invasion:
      involvement of nuclear liver X receptors.
AB  - Human embryonic implantation involves major invasion of the uterine wall and
      remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT).
      Abnormalities in these early steps of placental development lead to poor
      placentation and fetal growth defects and are frequently associated with
      preeclampsia, a major complication of human pregnancy. We recently showed that
      oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and
      inhibit cell invasion in a concentration-dependent manner. The aim of the present
      study was to better understand the mechanisms by which oxLDL modulate trophoblast
      invasion. We therefore investigated the presence of oxLDL receptors in our cell
      culture model of human invasive primary EVCT. We found using immunocytochemistry
      and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger
      receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We
      next examined the effect of low-density lipoprotein oxidative state on
      trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell.
      We demonstrated that only oxLDL containing a high proportion of oxysterols and
      phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X
      receptor (LXR) and peroxisomal proliferator-activated receptor gamma (PPARgamma),
      respectively, reduced trophoblast invasion. We next investigated the presence and
      the role of these nuclear receptors and found that in addition to PPARgamma,
      human invasive trophoblasts express LXRbeta, and activation of these nuclear
      receptors by specific synthetic or natural ligands inhibited trophoblast
      invasion. Finally, using a PPARgamma antagonist, we suggest that LXRbeta, rather
      than PPARgamma, is involved in oxLDL-mediated inhibition of human trophoblast
      invasion in vitro.

PMID- 15242984
TI  - Estrogen induces nitric oxide production via activation of constitutive nitric
      oxide synthases in human neuroblastoma cells.
AB  - Although it is becoming increasingly evident that nitric oxide (NO) mediates some
      of estrogen's actions in the brain, the effects of estrogen on NO production
      through NO synthases (NOS) in neuronal cells have not yet been identified. Here
      we assessed changes in NO production induced by 17beta-estradiol (E2) in cells of
      neuronal origin using human SK-N-SH neuroblastoma cells, which we show express
      all three isoforms of NOS. Involvement of NOS isoforms in E2-induced NO
      production was examined using isoform-specific NOS inhibitors. E2 (10(-10)-10(-6)
      m) induced rapid increases in NO release and changes in endothelial NOS (eNOS)
      expression, which were blocked by ICI 182,780, an antagonist of estrogen
      receptors. Increased levels of NO release and NOS activity induced by E2 were
      blocked by N5-(1-Imino-3-butenyl)-L-ornithine, a neuronal NOS inhibitor, and N(5)
      (1-Iminoethyl)-L-ornithine, an eNOS inhibitor, but not by 1400W, an inducible NOS
      inhibitor. These results demonstrate that E2-stimulated NO production occurs via
      estrogen receptor-mediated activation of the constitutive NOSs, neuronal NOS and
      eNOS. The E2-induced NO increase was abolished when extracellular Ca2+ was
      removed from the medium or after the addition of nifedipine, an L-type channel
      blocker, and was partially inhibited using 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid acetoxymethyl ester, an intracellular Ca2+ chelator.
      However, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl
      ester itself also caused an increase in NO release that was blocked by 1400W,
      suggesting that inducible NOS mediates this response. Together these data reveal
      that constitutive NOS activities are responsible for E2-induced NO production in
      neuroblastoma cells and that differential activation of NOS isoforms in these
      cells occurs in response to different treatments.

PMID- 15242985
TI  - Developmental and hormonally regulated messenger ribonucleic acid expression of
      KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent
      luteinizing hormone-releasing activity of KiSS-1 peptide.
AB  - The gonadotropic axis is centrally controlled by a complex regulatory network of
      excitatory and inhibitory signals that is activated at puberty. Recently, loss of
      function mutations of the gene encoding G protein-coupled receptor 54 (GPR54),
      the putative receptor for the KiSS-1-derived peptide metastin, have been
      associated with lack of puberty onset and hypogonadotropic hypogonadism. Yet the
      pattern of expression and functional role of the KiSS-1/GPR54 system in the rat
      hypothalamus remain unexplored to date. In the present work, expression analyses
      of KiSS-1 and GPR54 genes were conducted in different physiological and
      experimental settings, and the effects of central administration of KiSS-1
      peptide on LH release were assessed in vivo. Persistent expression of KiSS-1 and
      GPR54 mRNAs was detected in rat hypothalamus throughout postnatal development,
      with maximum expression levels at puberty in both male and female rats.
      Hypothalamic expression of KiSS-1 and GPR54 genes changed throughout the estrous
      cycle and was significantly increased after gonadectomy, a rise that was
      prevented by sex steroid replacement both in males and females. Moreover,
      hypothalamic expression of the KiSS-1 gene was sensitive to neonatal imprinting
      by estrogen. From a functional standpoint, intracerebroventricular administration
      of KiSS-1 peptide induced a dramatic increase in serum LH levels in prepubertal
      male and female rats as well as in adult animals. In conclusion, we provide novel
      evidence of the developmental and hormonally regulated expression of KiSS-1 and
      GPR54 mRNAs in rat hypothalamus and the ability of KiSS-1 peptide to potently
      stimulate LH secretion in vivo. Our current data support the contention that the
      hypothalamic KiSS-1/GPR54 system is a pivotal factor in central regulation of the
      gonadotropic axis at puberty and in adulthood.

PMID- 15242986
TI  - Cross-talk between phosphatidylinositol 3-kinase/AKT and c-jun NH2-terminal
      kinase mediates survival of isolated human islets.
AB  - Therapeutic strategies aimed at the inhibition of specific cell death mechanisms
      may increase islet yield and improve cell viability and function after routine
      isolation. The aim of the current study was to explore the possibility of AKT-JNK
      cross-talk in islets after isolation and the relevance of c-jun NH2-terminal
      kinases (JNK) suppression on islet survival. After routine isolation, increased
      AKT activity correlated with suppression of JNK activation, suggesting that they
      may be related events. Indeed, the increase in AKT activation after isolation
      correlated with suppression of apoptosis signal-regulating kinase 1 (ASK1), a
      kinase acting upstream of JNK, by phosphorylation at Ser83. We therefore examined
      whether modulators of phosphatidylinositol 3-kinase (PI3K)/AKT signaling affected
      JNK activation. PI3K inhibition led to increased JNK phosphorylation and islet
      cell death, which could be reversed by the specific JNK inhibitor SP600125. In
      addition, IGF-I suppressed cytokine-mediated JNK activation in a PI3K-dependent
      manner. We also demonstrate that inhibition of PI3K rendered islets more
      susceptible to cytokine-mediated cell death. SP600125 transiently protected
      islets from cytokine-mediated cell death, suggesting that JNK may not be
      necessary for cytokine-induced cell death. When administered immediately after
      isolation, SP600125 improved islet survival and function, even 48 h after removal
      of SP600125, suggesting that JNK inhibition by SP600125 may be a viable strategy
      for improving isolated islet survival. Taken together, these results demonstrate
      that PI3K/AKT suppresses the JNK pathway in islets, and this cross-talk
      represents an important antiapoptotic consequence of PI3K/AKT activation.

PMID- 15242987
TI  - Mechanisms of arginine-vasopressin-induced Ca2+ oscillations in beta-cells (HIT
      T15): a role for oscillating protein kinase C.
AB  - We examined the role of protein kinase C (PKC) for the generation of arginine
      vasopressin (AVP)-linked Ca2+ oscillations in beta-cells (HIT-T15). Activation of
      PKC by phorbol-12,13-dibutyrate (PDBu) reduced the frequency and finally
      abolished AVP-induced Ca2+ oscillations. The PKC inhibitors Go 6976, Ro-32-0432,
      or chelerythrine converted Ca2+ oscillations to a plateau-like rise in cytosolic
      free Ca2+, and PKC down-regulation reduced the percentage of cells exhibiting AVP
      induced Ca2+ oscillations. Several mechanisms were identified by which PKC could
      exert feedback on the AVP-linked Ca2+ oscillator. PDBu, but not the PKC
      inhibitors, inhibited AVP-stimulated inositol 1,4,5-trisphosphate production and
      mobilization of internal Ca2+. Ca2+ influx through voltage-sensitive Ca2+
      channels was attenuated by PDBu and PKC inhibitors, indicating complex PKC
      dependent regulation of voltage-sensitive Ca2+ channels involving stimulatory as
      well as inhibitory components. Furthermore, AVP caused oscillatory translocation
      of yellow fluorescent protein (YFP)-tagged PKCalpha and PKCbetaIota to the plasma
      membrane, which paralleled the Ca2+ oscillations in single cells. Repetitive
      translocation of YFP-PKCalpha and -PKCbetaIota could also be elicited by
      repetitive release of caged Ca2+. By contrast, AVP-stimulated translocation of
      YFP-PKCepsilon was monophasic, not synchronized with Ca2+ oscillations, and could
      not be mimicked by release of caged Ca2+. In conclusion, undisturbed activation
      of PKCs is a necessary intermediate to generate or maintain AVP-induced Ca2+
      oscillations in pancreatic beta-cells. The data further suggest that classical
      PKCs, predominantly by inhibition of inositol 1,4,5-trisphosphate production,
      provide the negative feedback required for AVP-induced Ca2+ oscillations to occur
      that is mediated by their repetitive activation by oscillating Ca2+
      concentrations.

PMID- 15242988
TI  - Extracellular signal-regulated kinases are involved in the acute activation of
      steroidogenesis in immature rat Leydig cells by human chorionic gonadotropin.
AB  - We studied the involvement of the ERK cascade in human chorionic gonadotropin
      (hCG)-induced steroidogenesis by primary cultures of immature rat Leydig cells.
      Our findings indicate that protein kinase A and protein kinase C function as
      upstream kinases in connection with transduction of the signal from the
      gonadotropin receptor to the ERK cascade. These MAPKs enhance the stimulatory
      effects of hCG on the de novo synthesis of the steroidogenic acute regulatory
      protein and the activity of protein phosphatase 2A, which are associated with
      increased androgen production by the Leydig cell. Specific inhibition of ERK1/2
      by Uo126 suppressed all of these cellular responses to hCG. In contrast,
      steroidogenesis from 22OHC (a cell-permeable form of cholesterol) is not
      inhibited by Uo126, suggesting that cholesterol delivery to mitochondria is being
      affected by this compound. We propose that the ERK cascade is an important part
      of the signal transduction pathway involved in the rapid hormonal responses of
      Leydig cells to trophic hormones. In hCG-activated Leydig cells, these MAPKs may
      play a role in controlling the biosynthesis of the steroidogenic acute regulatory
      protein as well as regulating protein phosphatase 2A activity, thereby governing
      cholesterol transport across the mitochondrial membrane.

PMID- 15242989
TI  - Role of growth hormone (GH) in liver regeneration.
AB  - Liver regeneration is a fundamental mechanism by which the liver responds to
      injury. This process is regulated by endogenous growth factors and cytokines, and
      it involves proliferation of all mature cells that exist within the intact organ.
      To understand the role of the GH/IGF-I axis in liver regeneration, we performed
      partial hepatectomies in three groups of mice: GH antagonist (GHa) transgenic
      mice, in which the action of GH is blocked; liver IGF-I-deficient mice that lack
      IGF-I specifically in the liver and also lack the acid-labile subunit (ALS;
      LID+ALSKO mice), in which IGF-I levels are very low and GH secretion is
      increased; and control mice. Interestingly, the survival rate of GHa transgenic
      mice was dramatically reduced after partial hepatectomy (57%) compared with the
      survival rate of controls (100%) or LID+ALSKO mice (88%). In control mice, the
      liver was completely regenerated after 4 d, whereas liver regeneration required 7
      d in LID+ALSKO mice. In contrast, in GHa mice, liver regeneration reached only
      70% of the original liver mass after 4 d and did not improve thereafter.
      Strikingly, 36 and 48 h after hepatectomy, the livers of control and LID+ALSKO
      mice, respectively, exhibited intense 5-bromo-2'-deoxyuridine (BrdU) staining,
      whereas BrdU staining was dramatically decreased in the livers of GHa-treated
      mice. These results suggest that GH plays a critical role in liver regeneration,
      although whether it acts directly or indirectly remains to be determined.

PMID- 15242990
TI  - Multilevel modelling and malaria: a new method for an old disease.
AB  - BACKGROUND: Malaria is influenced by a web of individual and ecological factors,
      i.e. factors relating to people and relating to environment. For a long time
      analysing these factors concurrently has raised statistical problems. Multilevel
      modelling provides a new attractive solution, which is still uncommon in tropical
      medicine. METHODS: Using an actual data set of 3864 individuals from 38 villages
      of the Highland Madagascar, a two-level modelling process is presented.
      Individual malaria parasitaemia is modelled step by step according to age
      (individual factor), altitude, and DDT indoor house-spraying status (village
      factors). RESULTS: The hierarchical organization of a data set in levels, fixed
      and random effects, and cross-level interactions are considered. Accurate
      estimations of standard errors, impact of unknown or unmeasured variables
      quantified and accounted for through random effects, are the highlighted
      advantages of multilevel modelling. CONCLUSION: While not denying the importance
      of understanding an aetiological chain, the authors recommend an increased use of
      multilevel modelling, mainly to identify accurately ecological targets for public
      health policy.

PMID- 15242991
TI  - The effect of human immunodeficiency virus on sperm parameters and the outcome of
      intrauterine insemination following sperm washing.
AB  - BACKGROUND: This is the first study to assess the outcome of sperm washing and
      intrauterine insemination (IUI) cycles in human immunodeficiency virus-positive
      (HIV(+)) men to determine any predictors of success, as well as evaluating the
      effect of HIV on sperm parameters. METHODS: Semen characteristics were evaluated
      in 106 HIV(+) men and a control group of 234 HIV(-) men, and the effect of
      markers of HIV disease assessed. Age, stimulation regime, sperm parameters,
      markers of HIV disease and the use of anti-retrovirals were assessed as
      predictors of the outcome of sperm washing/IUI cycles in the HIV(+) men. RESULTS:
      Ejaculate volume, sperm concentration, total count, progressive motility and
      normal morphology were all significantly higher in the control group compared to
      the HIV(+) men (P<0.05). A significant positive correlation was observed between
      CD4 count and sperm concentration, total count, motility, progressive motility
      type 'a'+'b' and post-preparation concentration and a significant negative
      correlation with normal sperm morphology of both raw and post-preparation
      samples. No correlation was observed between viral load (VL), years since
      diagnosis, use of anti-retrovirals or duration of use and any sperm parameter.
      The only factors that significantly improved IUI outcome were a VL <1000
      copies/ml and the use of anti-retrovirals. CONCLUSIONS: These data demonstrate
      that sperm parameters are significantly impaired by the presence of HIV infection
      and in particular correlate with CD4 count. Undetectable VL and the use of anti
      retrovirals improve the outcome of IUI/sperm washing in HIV(+) men.

PMID- 15242992
TI  - Prevalence of depressive and anxiety disorders in an assisted reproductive
      technique clinic.
AB  - BACKGROUND: Little is known about the prevalence of specific depressive and
      anxiety disorders in women before a new course of assisted reproductive
      technology treatment. Few studies have adopted the proper psychiatric diagnostic
      procedures. METHODS: All consecutive women visiting the assisted reproduction
      clinic of a university-affiliated medical centre, with the intention of starting
      a new assisted reproduction treatment course, were recruited. A psychiatrist made
      a diagnosis of psychiatric disorders using a structured interview, the Mini
      International Neuropsychiatric Interview (MINI). RESULTS: Of a total of 112
      participants, 40.2% had a psychiatric disorder. The most common diagnosis was
      generalized anxiety disorder (23.2%), followed by major depressive disorder
      (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity
      did not differ from those without in terms of age, education, income, or years of
      infertility. Women with a history of previous assisted reproduction treatment did
      not differ from those without in depression or anxiety. CONCLUSIONS: Depressive
      and anxiety disorders were highly prevalent among women who visited an assisted
      reproduction clinic for a new course of the treatment. Demographic features and a
      history of previous assisted reproduction treatment were not risk factors for
      these psychiatric morbidities in the assisted reproduction clinic.

PMID- 15242993
TI  - A prospective randomized study of laparoscopy and minilaparotomy in the
      management of benign adnexal masses.
AB  - BACKGROUND: Recent prospective and randomized studies have demonstrated that
      laparoscopy is better than laparotomy in the treatment of benign adnexal masses.
      The aim of this study is to analyse the perioperative outcomes of laparoscopy and
      minilaparotomy in these patients, in a prospective and randomized manner.
      METHODS: Between January 2003 and August 2003, 100 consecutive women with a
      diagnosis of presumed benign adnexal mass and requiring surgical treatment were
      randomly assigned to minilaparotomy and laparoscopy. Randomization was
      centralized and computer-based. RESULTS: All operative procedures were performed
      without conversion to laparotomy. In the group of patients submitted to
      minilaparotomy, a shorter operating time than patients submitted to operative
      laparoscopy (mean+/-SD: 71.9+/-31.8 versus 87.0+/-44.8 min; P<0.05) was found. On
      the other hand, there were significant differences in terms of postoperative
      ileus (1.1+/-0.4 days in laparoscopy and 1.4+/-0.6 in minilaparotomy P<0.023),
      without affecting the day of discharge. No intraoperative or early complications
      were registered in either group. CONCLUSIONS: Taking into account that
      laparoscopy has to be considered the first choice for benign adnexal surgery, our
      data suggest that minilaparotomy could offer the gynaecology surgeon a valid
      alternative in the minimally invasive surgery field, especially in specific
      settings.

PMID- 15242994
TI  - Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women
      with endometriosis.
AB  - BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the
      peritoneal cavity is a possible etiologic factor for development of
      endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect
      by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and
      DR5. In the present study, we addressed the possibility that the TRAIL/OPG system
      is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG
      and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis
      were measured using specific enzyme-linked immunoabsorbent assay. The expression
      of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription
      polymerase chain reaction. RESULTS: OPG concentrations in PF of women with
      endometriosis were significantly higher than those of women without endometriosis
      (P=0.006). With respect to the stages of the disease, the concentrations of OPG
      in women with stage III/IV endometriosis were significantly higher than in those
      without endometriosis and those with stage I/II endometriosis. On the other hand,
      the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV
      endometriosis compared to those in non-endometriosis and stage I/II
      endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic
      tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is
      involved in the pathophysiology of endometriosis, possibly affecting the
      apoptosis of endometriotic cells.

PMID- 15242995
TI  - Soluble factors from human endometrium promote angiogenesis and regulate the
      endothelial cell transcriptome.
AB  - BACKGROUND: Angiogenesis and vascular remodeling play critical roles in the
      cyclical growth and regression of endometrium. They also appear to play roles in
      the pathogenesis of endometriosis. METHODS AND RESULTS: Supernatants were
      collected from cultured endometrium isolated from women with and without
      endometriosis. These supernatants induced endothelial cell proliferation and
      angiogenesis in vitro. They contained vascular endothelial growth factor (VEGF)
      A, and their proliferative effects on endothelial cells were partially abrogated
      by a blocking anti-VEGF-A antibody. Gene array analysis showed that culture
      supernatants from proliferative phase endometrium, and to a lesser extent
      secretory phase endometrium, induced significant changes in the transcriptome of
      endothelial cells. We could not detect any association between endometriosis and
      the ability of endometrial-derived soluble factors to promote angiogenesis or to
      regulate the endothelial transcriptome. In addition, we could not detect any
      association between endometriosis and the concentration of VEGF-A in supernatants
      from cultured endometrium or in menstrual effluent. CONCLUSIONS: We have shown
      that endometrium cultured in vitro produced soluble factors, including VEGF-A,
      that promoted angiogenesis. Proliferative phase endometrium promoted significant
      endothelial cell transcriptome changes that appear overall to be pro-angiogenic.
      These transcriptome changes provide insight into the dynamic control of vessel
      structure on which both eutopic endometrium and endometriotic lesions depend.

PMID- 15242996
TI  - Cytoplasmic droplets are normal structures of human sperm but are not well
      preserved by routine procedures for assessing sperm morphology.
AB  - BACKGROUND: There is a discrepancy between the use of terminology employed by
      clinicians and basic scientists concerning the cytoplasmic droplets of sperm.
      Most clinicians consider their presence on sperm to be indicative of abnormal
      sperm, whereas basic scientists consider them to be attributes of normal sperm.
      METHODS: The presence of cytoplasmic droplets on human sperm was examined using
      conventional air-dried, fixed and stained sperm smears and in living and fixed
      wet preparations. RESULTS: Cytoplasmic droplets were found on the majority of
      motile sperm and in fixed preparations but only half of them were found in air
      dried smears. There was no relationship between the presence of abnormally large
      cytoplasmic droplets, indicative of abnormal sperm, and the droplets found on
      living cells. CONCLUSION: The term 'cytoplasmic droplet' is confusingly used to
      describe two different sperm structures: large amounts of retained, excessive
      cytoplasmic remnants, that survive the air-drying procedure and are observed on
      abnormal sperm in conventionally stained sperm smears, and osmotically sensitive
      vesicles that are present on normal living sperm. A plea is made to retain the
      term 'cytoplasmic droplet' for the latter structure of normal sperm and to use
      the term 'excess residual cytoplasm' to describe the abnormally retained
      cytoplasm observed on abnormal sperm in smears.

PMID- 15242997
TI  - Inhibiting MMP activity prevents the development of endometriosis in the chicken
      chorioallantoic membrane model.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are essential for extracellular
      matrix remodelling and may contribute to the development of endometriosis.
      Transplantation of endometrium onto the chicken chorioallantoic membrane (CAM)
      results in endometriosis-like lesion formation, a process that requires extensive
      tissue remodelling. We investigated the expression of a wide range of MMPs in
      menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal
      endometriosis and in endometriosis in the rectovaginal space, as well as the
      function of MMPs in early lesion formation in the CAM model. METHODS: Expression
      of MMPs was evaluated by immunohistochemistry and MMP function was studied in the
      CAM by inhibiting MMP activity during lesion formation. RESULTS: Nearly all MMPs
      were present in all tissues studied. No significant differences in the expression
      of a majority of MMPs were found in endometriosis-like lesions in CAMs when
      compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13
      activities significantly impaired endometriosis-like lesion formation in CAMs.
      CONCLUSIONS: The MMP expression profiles of experimentally induced endometriosis
      in CAMs and human endometriosis are similar. The prevention of endometriosis-like
      lesion formation in the CAM by inhibiting MMP activity strongly suggests that
      MMPs have a function in the early development of endometriotic lesions.

PMID- 15242998
TI  - Uterine leiomyoma and menstrual cycle characteristics in a population-based
      cohort study.
AB  - BACKGROUND: We examined the association of uterine leiomyoma with menstrual cycle
      characteristics in a population of non-care-seeking women. METHODS: This cross
      sectional study uses data from the Seveso Women's Health Study (SWHS), a
      population-based cohort in Italy. Participants included 341 premenopausal women,
      30-60 years old, who had an intact uterus and were not pregnant, lactating, or
      using oral contraception or intra-uterine devices. We examined the presence of
      any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual
      cycle length, flow length and heaviness of flow. The association of leiomyoma
      number, volume, tissue layer location and axial position with menstrual cycle
      characteristics was also examined. RESULTS: Uterine leiomyomata were detected in
      73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma
      was not significantly related to menstrual cycle length, flow length or heaviness
      of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8
      4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number,
      volume, tissue layer location (subserosal or intramural) and axial position
      (anterior or posterior) of the leiomyoma were also not related to menstrual cycle
      characteristics. CONCLUSION: In this Italian population of women not seeking
      gynaecological care, menstrual characteristics are not related to leiomyoma.

PMID- 15242999
TI  - Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene
      citrate-resistant polycystic ovary syndrome. Impact on women's health-related
      quality of life.
AB  - BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment
      strategy for women with clomiphene citrate (CC)-resistant polycystic ovary
      syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative
      treatment modality, leading to a comparable cumulative pregnancy rate. In
      deciding which treatment to opt for, women's health-related quality of life
      (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women
      with PCOS were randomly assigned to receive either the electrocautery strategy,
      entailing laparoscopic electrocautery of the ovaries followed by CC and
      recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with
      rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36,
      Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression
      Scale, administered before randomization and 2, 12 and 24 weeks thereafter.
      RESULTS: The intention to treat analysis revealed no significant differences
      between the treatment groups on any of the scales at any point during follow-up.
      In women without an ongoing pregnancy, those treated with rFSH showed
      significantly more depressive symptoms than women allocated to the electrocautery
      strategy, with or without CC, although differences were small. CONCLUSIONS:
      Overall, HRQoL was not affected in both groups. In women still under treatment,
      rFSH was slightly more burdensome for women's HRQoL than electrocautery with or
      without CC.

PMID- 15243000
TI  - Fertility and pregnancy outcomes in men and women with cystic fibrosis in the
      United Kingdom.
AB  - BACKGROUND: The survival of patients with cystic fibrosis (CF) now occurs into
      the fourth decade of life. Our aim was to evaluate the fertility and pregnancy
      outcomes of men and women with cystic fibrosis within a large British cohort.
      METHODS: A population based cohort study of 4659 males and females registered
      with the UK Cystic Fibrosis Database in 2001. RESULTS: Poor respiratory health
      (forced expiratory volume in 1 s FEV1 <50%) and CF-related diabetes increased
      significantly post-puberty compared with childhood. Few individuals with CF
      sought fertility treatment (1% men, 0.5% women) or achieved pregnancies (1.3% of
      partners of men, 5.7% women). However, the majority of pregnancies had a good
      outcome (67% live term birth among male partners, 74% among women). Women who
      achieved a pregnancy were less likely to suffer from poor respiratory health
      (FEV1 <50%), age adjusted Odds Ratio 0.6 (95% CI 0.3-0.9), less likely to be
      homozygous for the DF508 genotype OR 0.5 (95% CI 0.3-0.9) and had a significantly
      earlier median age at diagnosis (0 years vs 2 years, P=0.001). CONCLUSIONS:
      Increasing numbers of males and females with cystic fibrosis are reaching
      reproductive age but currently very few have a child. Optimal adult health should
      improve the reproductive prognosis for both men and women.

PMID- 15243001
TI  - Preferential transfer of endogenous ovarian steroid hormones to the uterus during
      both the follicular and luteal phases.
AB  - BACKGROUND: Ovarian steroids are thought to be released into the systemic
      circulation and reach the uterus via the uterine arteries. However, results of
      experimental and clinical studies suggest the existence of local transfer of
      steroids from the ovary to the uterus. This study aimed to verify the existence
      of preferential distribution of ovarian steroids to the uterus in the two phases
      of the menstrual cycle. METHODS: We performed parallel measurements of serum
      levels of estradiol and progesterone in the systemic circulation (arterial and
      venous) and in the uterine vessels in two groups of cycling women; one group were
      in the follicular phase (six women) and the other group were in the luteal phase
      (10 women) of the menstrual cycle. RESULTS: Both in the follicular phase and in
      the luteal phase groups, mean estradiol levels in the uterine blood were
      significantly higher than in both sides of the systemic circulation (F = 7.30, df
      = 15, P < 0.006; and F = 4.70, df = 27, P < 0.02). Similar results were obtained
      in the luteal phase group for progesterone (F = 9.38, df = 27, P < 0.0001). Both
      estradiol and progesterone levels in arterial and venous systemic blood were
      similar. CONCLUSIONS: The results of this study demonstrate that ovarian steroid
      levels are significantly higher in the uterine vessels than in both sides of the
      systemic blood circulation, and strongly suggest the existence in the female
      pelvis of mechanisms of local distribution of ovarian hormones.

PMID- 15243002
TI  - Pregnancy outcome after blastocyst transfer as compared to early cleavage stage
      embryo transfer.
AB  - BACKGROUND: Retrospective cohort study to evaluate differences in outcome when
      embryo transfer was performed either on day 2-3 (cleavage stage, CS-group) or on
      day 4-5 (blastocyst stage, BS-group). METHODS: A total of 1259 consecutive cycles
      yielding 500 live born babies performed at a single centre in Bregenz, Austria,
      were included. Main outcome measures were implantation and (multiple) pregnancy
      rates and neonatal outcome including birth defects. RESULTS: Total Pregnancy rate
      was 44% vs 28% (P < 0.001) and the total 'take home baby rate' was 37% vs 22% in
      the BS-group and the CS-group, respectively. Rate of multiple gestations (34% vs
      17%, P = 0.001) was significantly higher among the BS-group, resulting in a
      higher rate of preterm deliveries < 36 weeks (26% vs 17%, P = 0.045). Female
      factor causing infertility (40% vs 21%, P < 0.001) was significantly higher among
      the BS-group. For the CS-group, rate of singleton pregnancies (83% vs 66%, P =
      0.001) and idiopathic cause of infertility (34% vs 22%, P = 0.012) were
      significantly higher. No statistically significant differences were found in sex,
      Caesarean section rate, Apgar score and umbilical artery pH-values, total mean
      birth weight, admission rate to intensive care unit, days of hospitalization and
      number of minor and major birth defects. CONCLUSIONS: Our data suggest that
      blastocyst transfer may lead to a higher pregnancy rate with an overall better
      take-home baby rate (THBR) at the cost of higher rates of multiples and preterm
      deliveries.

PMID- 15243003
TI  - What is the most relevant standard of success in assisted reproduction? Singleton
      live births should also include preterm births.
AB  - An intensive debate is ongoing in this journal concerning the most appropriate
      endpoint after assisted reproduction techniques. The endpoint suggested by the
      first authors was Birth Emphasizing a Successful Singleton at Term (BESST). We
      have evaluated the most appropriate endpoint from different perspectives:
      patients, public, health authorities, obstetric and IVF clinics. We find
      singleton live birth highly relevant as an outcome parameter as multiple
      pregnancies are the main factor responsible for the overall poorer obstetric and
      neonatal outcome in IVF pregnancies, and multiple pregnancies are mostly an
      avoidable iatrogenic complication. However, our proposal is that both preterm and
      term singletons should be included since the prematurity rate is an outcome that
      is largely uninfluenced by the IVF clinics. In conclusion, we propose singleton
      live birth per cycle initiated as the most appropriate main outcome after
      assisted reproduction. Prematurity should in addition be reported separately as a
      secondary outcome.

PMID- 15243004
TI  - Influence of the number of motile spermatozoa inseminated and of their morphology
      on the success of intrauterine insemination.
AB  - BACKGROUND: Although intrauterine insemination (IUI) is one of the most common
      assisted reproductive technology methods in the world, the relative influence of
      various semen characteristics on the likelihood of a successful outcome is
      controversial. The aim of our study was to assess the results of IUI as a
      function of both the number of motile spermatozoa inseminated (NMSI) and the
      percentage of morphologically normal spermatozoa after preparation. METHODS: This
      was a retrospective study of 889 couples who underwent 2564 IUI cycles of ovarian
      stimulation with HMG or recombinant FSH in our centre between January 1991 and
      December 2000. RESULTS: A total of 331 clinical pregnancies were obtained, for a
      pregnancy rate/cycle of 12.91%. When the NMSI was < 1 x 10(6), the pregnancy
      rate/cycle was significantly lower (3.13%) than in any of the subgroups with NMSI
      > or = 2 x 10(6). Sperm morphology, assessed before or after preparation, was not
      in itself a significant factor that affected the likelihood of IUI success.
      Nonetheless, when the post-migration rate of normal sperm was < 30%, the
      pregnancy rate/cycle was 5.43% when NMSI was < 5 x 10(6) and 18.42% when NMSI was
      > or = 5 x 10(6) (P = 0.008). Pregnancy rates did not differ significantly
      according to NMSI when the percentage of normal sperm after preparation was > or
      = 30%, or according to percentage of normal sperm when the NMSI was > or = 5 x
      10(6). CONCLUSIONS: Our results show that a minimum of 5 x 10(6) motile
      spermatozoa should be inseminated when the normal morphology of the sperm after
      preparation is < 30%; the quantity compensates at least in part for the defective
      quality. If this threshold of NMSI cannot be obtained, IVF should be recommended.

PMID- 15243005
TI  - Advanced glycation end products induce secretion of chemokines and apoptosis in
      human first trimester trophoblasts.
AB  - BACKGROUND: We studied the effects of advanced glycation end products (AGEs),
      which are known to accumulate in patients with diabetes, autoimmune diseases, or
      that smoke, on human trophoblasts. METHODS: First trimester human chorionic villi
      of 6-10 week gestation were obtained. Expression and localization of the receptor
      for AGEs (RAGE) was examined by western blotting and immunohistochemistry.
      Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, regulated upon
      activation, normal T-cell expressed and secreted (RANTES), and human chorionic
      gonadotropin (hCG) in culture medium were measured by ELISA. Trophoblastic
      apoptosis was evaluated by the Hoechst 33258 staining and the in situ nick end
      labeling technique. RESULTS: RAGE was localized in trophoblasts. AGEs
      significantly stimulated secretion of both MIP-1alpha and MIP-1beta from
      trophoblasts in a time- and dose-dependent manner. AGEs significantly induced
      apoptosis and reduced secretion of hCG. Increased secretions of MIP-1alpha and
      MIP-1beta by AGEs were significantly suppressed by inhibitors of nitric oxide
      synthase (NOS) or nafamostat mesilate, a synthetic serine protease inhibitor and
      a suppressor of transcription factor, NF-kappaB activation. These agents also
      suppressed the effects of AGEs on hCG secretion and trophoblastic apoptosis.
      CONCLUSIONS: These AGE-mediated changes in trophoblasts may lead to impairment of
      implantation and placentation. NOS inhibitors or nafamostat mesilate may modify
      these effects.

PMID- 15243006
TI  - Chromosomal abnormality rate in human pre-embryos derived from in vitro
      fertilization cycles cultured in the presence of Follicular-Fluid Meiosis
      Activating Sterol (FF-MAS).
AB  - BACKGROUND: The objective of the study was to investigate the effect of
      Follicular-Fluid Meiosis Activating Sterol (FF-MAS) when added to the culture
      media on the incidence of chromosomal abnormalities and pre-embryo development in
      human pre-embryos. METHODS: 243 women undergoing IVF/ICSI treatment donated 353
      oocytes in a multicentre, prospective, randomized, double blind, four-arm,
      controlled trial performed at Danish and Swedish public and private IVF centers.
      Metaphase II oocytes were randomly assigned to: FF-MAS 5 microM, FF-MAS 20
      microM, ethanol 0.2% (vehicle control) or water for injection (inert control).
      The exposure regimen of FF-MAS to the human oocytes was 4 h prior to
      fertilization by ICSI and 20 h exposure post ICSI. The primary endpoint was the
      incidence of numerical chromosomal abnormalities. Secondary endpoints were
      cleavage rate and pre-embryo quality. RESULT: On the pre-embryo level, no
      significant differences in chromosomal abnormality rate were observed among the
      four groups. However, the percentage of uniformly normal pre-embryos was
      significantly lower in the pooled FF-MAS group (5 microM: 12% and 20 microM: 17%)
      than in the pooled control group (inert control 32% and vehicle control 42%). A
      high level of mosaicism (41-60%) was found in all groups. At the blastomere
      level, the percentage of blastomeres categorized as normal was significantly
      lower in the FF-MAS 5 microM group (41%) and the FF-MAS 20 microM (29%) group
      versus the inert (52%) and the vehicle (61%) groups. Significantly reduced
      cleavage and good quality pre-embryo rates were found in both FF-MAS groups.
      CONCLUSION: FF-MAS increased the rate of aneuploidy and had detrimental effects
      on cleavage and pre-embryo development, when exposed both before and after
      fertilization.

PMID- 15243008
TI  - Early cleavage is a valuable addition to existing embryo selection parameters: a
      study using single embryo transfers.
AB  - BACKGROUND: To reduce the twin pregnancy rate, elective single embryo transfer
      (eSET) is increasingly implemented. Improvement of the results obtained with eSET
      can be achieved by better selection of the most viable embryo. This study
      investigated the predictive value of early cleavage (EC) as an additional
      parameter for selecting the embryo with the highest implantation potential by
      using data from SET's. METHODS: Data from 165 SET's were retrospectively
      evaluated. Cleavage to the 2-cell stage was determined 23-26 h after injection or
      25-28 h after insemination. Selection of the embryo to be transferred was based
      on cell morphology and cell number on the day of transfer, not on the EC status.
      Additional information on the predictive value of EC on developmental potential
      was obtained by analysing 253 transfers with two embryos (double embryo transfer,
      DET) and blastocyst formation of 1160 surplus embryos. Logistic regression was
      used to determine the predictors of pregnancy or blastocyst development. RESULTS:
      A significantly higher pregnancy rate was observed after transfer of single EC
      embryos compared to single non-EC embryos (46 versus 18%). This result was
      confirmed by the significantly higher pregnancy rate after DET with two EC
      embryos as compared to DET with two non-EC embryos (45 versus 25%) and the
      blastocyst formation of EC embryos compared to non-EC embryos (66 versus 40%).
      Logistic regression showed that EC is an independent predictor for both pregnancy
      and blastocyst development in addition to cell morphology and cell number.
      CONCLUSIONS: In order to improve the selection of the embryo with the highest
      implantation potential, selection for transfer should not be based on cell number
      and morphology on the day of transfer alone, but also on early cleavage status.

PMID- 15243007
TI  - Effect of age on ovarian stromal flow measured by three-dimensional ultrasound
      with power Doppler in Chinese women with proven fertility.
AB  - BACKGROUND: Increasing age is associated with reduced ovarian stromal blood flow
      detected by three-dimensional (3D) power Doppler ultrasound in infertile
      patients. However, little information exists in the literature regarding the
      effect of age on the ovarian stromal blood flow in fertile women. METHODS: On the
      second to fourth day of their menstrual cycle, fertile Chinese women who had
      regular monthly cycles and no history of tubal and ovarian surgery underwent a
      transvaginal scan with 3D power Doppler to determine total antral follicle count
      (AFC), total ovarian volume, total ovarian vascularization index (VI)/flow index
      (FI)/vascularization flow index (VFI). Serum FSH and vascular endothelial growth
      factor concentrations were checked. RESULTS: Out of 177 women scanned, 138 women
      were included in the final analysis. Total AFC and serum FSH were significantly
      different among four age groups (< or = 30, 31-35, 36-40 and > or = 41 years).
      Total ovarian VI and VFI were significantly lower in women aged > or = 41 years.
      AFC had the best correlation with the age of women, followed by serum FSH
      concentration and ovarian 3D power Doppler indices. The rate of decline of total
      ovarian VI was 0.18% per year. CONCLUSION: Ovarian stromal blood flow was
      significantly reduced only in women aged > or = 41 years.

PMID- 15243009
TI  - Posthumous sperm retrieval for the purpose of later insemination or IVF in
      Israel: an ethical and psychosocial critique.
AB  - In October 2003, the Attorney General of the Government of Israel published
      guidelines allowing posthumous sperm retrieval for the purpose of later
      insemination or IVF by the surviving female partner. This paper presents an
      ethical and psycho-social critique of the guidelines, which challenges their
      basic premise that personal autonomy over-rides any other ethical principle and
      argues that the autonomy of the adult should not over-ride the well-being of the
      offspring. It also shows that, despite the centrality of autonomy in the
      guidelines, they actually infringe on the autonomy of the deceased, and pose
      challenges to that of the surviving partner. It questions the propriety and very
      possibility of ascertaining the 'presumed wishes' of the deceased for a
      posthumous child. Finally, it argues against the document's presentation of
      posthumous sperm retrieval as a medical procedure and contends that, on the
      contrary, medicine and science are suborned to the exploitation of the dead.

PMID- 15243010
TI  - Controlled-release methylphenidate improves attention during on-road driving by
      adolescents with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a
      3- to 4-fold increase in both driving-related accidents and associated injuries.
      Methylphenidate (MPH) is the most commonly prescribed psychostimulant medication
      for ADHD. It has been demonstrated to improve performance on a driving simulator.
      This study investigated whether a once-daily, long-acting, osmotic, controlled
      release MPH formulation improves the driving performance of ADHD adolescents
      while driving their own car on an actual road segment. METHODS: Twelve ADHD
      diagnosed male adolescent drivers (mean age, 17.8 years) prescribed a standard
      dose of 1.0 mg/kg (if they were not already taking methylphenidate) of controlled
      release MPH participated in this repeated-measures crossover study. On 2 separate
      occasions (off/on medication randomized), participants drove a standard 16-mile
      road course incorporating rural, highway, and urban streets. A rater, blind to
      medication conditions, sat in the back seat and rated impulsive (eg, "cutting
      off" another driver) and inattentive (eg, drove past designated turn) driving
      errors. RESULTS: Impulsive driving errors were observed to occur rarely under
      both medication and no medication conditions. Inattentive driving errors were
      more common and were significantly reduced while the subject was on medication
      (4.6 versus 7.8; P <.01). The improvement in driving performance (change in
      number of errors recorded) from first to second testing was positively correlated
      with medication dosage (r = 0.60; P <.01). CONCLUSIONS: Once-daily controlled
      release MPH improves real-life driving performance of adolescent males diagnosed
      with ADHD. In particular, it significantly reduces driving errors arising from
      inattention.

PMID- 15243011
TI  - Guaifenesin as a treatment for primary dysmenorrhea.
AB  - BACKGROUND: Dysmenorrhea is highly prevalent and causes much work loss and
      discomfort. A treatment with a new mechanism of action could benefit women of
      menstruating age. A study was undertaken to assess the efficacy of guaifenesin as
      a treatment for primary dysmenorrhea because of its effects of cervical dilation
      and cervical mucous thinning. METHODS: Thirty-four subjects with primary
      dysmenorrhea were enrolled in a double-blind, placebo-controlled study. Three
      treatment surveys measured 10 symptoms (lower abdominal pain, general abdominal
      pain, back pain, headache, nausea, diarrhea, constipation, menstrual flow,
      weakness, and activities of daily living) on a 100-mm visual analog scale.
      Nonstudy analgesic use was also measured. RESULTS: Twenty-five subjects returned
      the first treatment survey, and 17 returned all 3 surveys. Results were
      nonsignificant, but guaifenesin trended toward being better than placebo for
      dysmenorrhea pain and associated constitutional symptoms and caused no worsening
      of symptoms. Lower abdominal mean pain scores from the first survey decreased 38
      mm for guaifenesin versus 7 mm for placebo. By the third survey, only 2 of 8
      guaifenesin participants took nonstudy analgesics compared with all 9 placebo
      subjects. CONCLUSIONS: Guaifenesin may be useful in the treatment of primary
      dysmenorrhea. A larger study is needed to validate these initial findings.

PMID- 15243012
TI  - Carbohydrate-deficient transferrin: validity of a new alcohol biomarker in a
      sample of patients with diabetes and hypertension.
AB  - OBJECTIVE: To test the reliability and validity of a new alcohol biomarker.
      DESIGN: Cross-sectional with matched control. Alcohol use, symptoms of alcohol
      dependence, health status, current medications, carbohydrate-deficient
      transferrin (CDT) levels, and gamma-glutamyl transferase levels were assessed.
      Validity of the %CDT test was estimated using a drinking cutoff of 90 or more
      drinks in the previous 30 days. PARTICIPANTS: Sample (n = 799) included 89
      patients with type 2 diabetes, 299 patients with hypertension, 209 patients with
      hypertension and type 2 diabetes, and 202 matched control subjects with neither
      diabetes nor hypertension. RESULTS: Three hundred ninety-six women and 403 men
      ages 30 to 60 participated in the study. Six percent (45 of 799) reported
      drinking more than 14 drinks per week, 2% (n = 17) met criteria for alcohol
      abuse, and 3% (n = 23) met DSM-IV criteria for dependence. The overall
      sensitivity of the %CDT test was 61% with a specificity of 85%. A receiver
      operating characteristic curve was used to determine that the best fit was for
      persons who reported >90 drinks per month and a CDT level >2.5% with an area
      under the curve of 0.83. Test-retest reliability (R) was 0.94. CONCLUSIONS: %CDT
      levels are useful in detecting and/or confirming high-risk drinking in patients
      being treated for type 2 diabetes and hypertension.

PMID- 15243013
TI  - Radiographs in the office: is a second reading always needed?
AB  - BACKGROUND: We evaluated the frequency, nature, and importance of the changes in
      patient care that occurred as a result of differences in outpatient radiograph
      readings for cases in which the primary care clinician, hypothetically, would not
      request a second reading by a radiologist. METHODS: During 4 months, 1393 pairs
      of radiographic readings were collected from 9 volunteer primary care practices
      with 86 clinicians and a second reading by one of 42 radiologists. For 553,
      hypothetically, the clinician would not request a consultation from a
      radiologist. Review analysis of the 553 pairs revealed 100 (18.1%) radiographs in
      which the radiologist's reading did not agree with the clinician's reading. Data
      from the original visit and subsequent related care were abstracted from patient
      charts and reviewed. Changes in clinical care resulting from the radiologist's
      reading were identified. RESULTS: The radiologists' second reading of these 553
      sets of radiographs resulted in 14 (2.5% of 553 and 14% of 100) cases of one or
      more changes in care. We found 38 documented or presumed changes in care and zero
      substantial changes in care. CONCLUSIONS: Primary care clinicians are able to
      identify radiographs for which a second reading by a radiologist will not result
      in substantial changes in care.

PMID- 15243014
TI  - Smoking cessation in pregnancy: a review of postpartum relapse prevention
      strategies.
AB  - OBJECTIVE: Review and examine existing research, current strategies, and
      directions for future research on smoking cessation relapse and relapse
      prevention in pregnancy and postpartum. METHODS: A MEDLINE/PubMed search in 2002
      and 2003 for articles containing the key words "smoking," "pregnancy,"
      "cessation," and "cessation relapse prevention" and references of retrieved
      papers yielded a review of more than 500 articles. Only 14 of these addressed
      program-based strategies to increase cessation among pregnant women through
      relapse prevention programs. CONCLUSION: Although there is much information on
      the rationale and strategies for smoking cessation for pregnant women, fewer
      studies exist on how to prevent relapse. Maintaining and accelerating progress in
      cessation during pregnancy and postpartum requires more research that focuses on
      relapse prevention and cessation. Programs should incorporate stresses particular
      to postpartum women, should be part of routine health care, and should involve
      the woman's social support network, including her partner, to maximize
      effectiveness.

PMID- 15243015
TI  - Advanced life support in obstetrics in Ecuador: teaching the teachers.
AB  - The advanced life support in obstetrics (ALSO) course is designed to help
      maternity care providers prepare for obstetrical emergencies. A team of 12 US
      physicians and a medical interpreter recently taught the ALSO course in Ecuador,
      with the goal of addressing Ecuador's high maternal and infant mortality rates.
      To have a greater impact, a teach-the-teacher model was used so that Ecuadorian
      physicians can now hold their own ALSO courses. In the process of implementing
      the courses, valuable lessons were learned which can be applied to future ALSO
      courses in developing countries and in the United States.

PMID- 15243016
TI  - Zebras on the commons: rare conditions in family practice.
AB  - BACKGROUND: Family physicians (FPs) specialize in the management of common
      problems, but we know little about their role in the care of patients with rare
      conditions. OBJECTIVE: To describe the roles FPs play in the identification and
      management of patients with rare conditions in a typical practice. METHODS:
      Office record review of 100 patients with rare conditions in the everyday,
      community-based, private practice of 4 FPs. Analysis of patient demographic
      characteristics, diagnoses, and the roles played by the FP in the patient's care,
      including diagnosis, treatment, referral, and long-term patient management.
      RESULTS: These FPs cared for patients with a wide variety of rare disorders
      across the spectrum of patient age and sex, organ system involved, and medical
      specialty area. FPs identified the problem in 89%, diagnosed the disorder in 54%,
      provided acute care in 56%, and provided continuing care for 76% of patients. FPs
      consulted other physicians in 85% of cases. The condition was life threatening in
      58% of patients. CONCLUSIONS: Family physicians provide a broad range of services
      to a wide variety of patients with rare medical problems.

PMID- 15243017
TI  - Influenza vaccination in pregnancy: current practices in a suburban community.
AB  - PURPOSE: The Centers for Disease Control (CDC) identify women in their second and
      third trimesters as a high-risk population warranting influenza vaccination. This
      study attempted to characterize understanding of these guidelines and obstacles
      to their implementation in a suburban community. METHODS: Family physicians and
      obstetricians with admitting privileges to a community-based hospital were
      surveyed regarding estimated vaccine availability and administration in their
      practices and regarding knowledge of indications and contraindications to
      influenza vaccination in pregnancy. RESULTS: Of the 20 obstetricians and 66
      family physicians completing the survey, 68.4% of obstetricians and 90.5% of
      family physicians carried the vaccine in their offices (P =.027). Both
      obstetricians and family physicians incorrectly perceived multiple factors as
      contraindications to influenza vaccination in pregnancy. Obstetricians and family
      physicians reported similar proportions of their pregnant patients received the
      vaccine (35 versus 40%). CONCLUSIONS: In this study, more family physicians had
      the influenza vaccine available than obstetricians, but there was no difference
      in estimated rates of vaccination during pregnancy or in the understanding of its
      indications and contraindications. Finally, no physicians in our community
      reported providing influenza vaccination in pregnancy at recommended frequencies.
      Further research is needed to clarify methods of improving vaccination rates in
      both family practice and obstetric settings.

PMID- 15243018
TI  - Obstructive sleep apnea in pregnancy.
AB  - A 25-year-old woman, gravida 4 para 2, at 37 weeks gestation was evaluated and
      treated for preeclampsia. Overnight, the patient had a witnessed apneic episode
      with maternal oxygen desaturation and concurrent fetal heart rate deceleration.
      She subsequently delivered an infant that was small for gestational age. This is
      the first case described with confirmed obstructive sleep apnea by formal
      polysomnography and witnessed maternal desaturation with fetal heart rate
      decelerations. Recognizing obstructive sleep apnea (OSA) early in gestation will
      help dictate treatment options and may prevent adverse maternal fetal outcomes.
      Continuous positive airway pressure (CPAP) seems to be a safe treatment with
      minimal adverse effects. Questioning of patients at the first prenatal visit and
      monitoring for increased snoring during gestation may help detect early signs and
      symptoms of OSA. Treatment of OSA with CPAP might improve perinatal outcomes.

PMID- 15243019
TI  - Cerebral venous thrombosis as a cause of acute headache.

PMID- 15243020
TI  - Subacromial/subdeltoid septic bursitis associated with isotretinoin therapy and
      corticosteroid injection.

PMID- 15243021
TI  - Recurrent herpes simplex type 2 virus (Mollaret) meningitis.

PMID- 15243022
TI  - Factor V Leiden mutation and pregnancy.

PMID- 15243024
TI  - No significant decrease in antibiotic use from 1992 to 2000, in the French
      community.
AB  - OBJECTIVES: To analyse trends in antibiotic exposure of the French population
      from 1992 to 2000. METHODS: The analysis used data provided by a representative
      annual nationwide survey of health care consumption in the community. RESULTS:
      The frequency of antibiotic use increased from 4.7 per 100 person-months in 1992
      to 7.3 in 1995, and remained stable from 1998 to 2000. Children under 7 years of
      age were three times more strongly exposed to antibiotics than older subjects.
      Respiratory tract infections of probable viral aetiology and sore throat
      accounted for >50% of antibacterial prescriptions. CONCLUSIONS: We identified two
      major priorities for campaigns designed to reduce antibiotic exposure of the
      French population in the community, namely respiratory tract infections of
      presumed viral origin, and children under 7 years of age.

PMID- 15243023
TI  - Dissemination amongst humans and food products of animal origin of a Salmonella
      typhimurium clone expressing an integron-borne OXA-30 beta-lactamase.
AB  - OBJECTIVES: Characterization of the molecular basis for beta-lactam resistance
      and evaluation of the clonal relatedness among nine isolates of multidrug
      resistant Salmonella typhimurium recovered from seven clinical human samples and
      two pork end products. METHODS: The isolates were examined for susceptibility to
      antimicrobial agents. The relationships between resistance genes, class 1
      integrons, plasmids and isolates were screened by molecular methods such as
      polymerase chain reaction and restriction fragment length analysis. RESULTS: A
      bla(OXA-30) gene, located in a class 1 integron, was detected in all isolates.
      This integron was present on a conjugative plasmid in all but one isolate. By
      pulsed-field gel electrophoresis, it was determined that all strains share the
      same chromosomal type. CONCLUSIONS: This study demonstrates the spread of an OXA
      30-producing S. typhimurium in Portugal, suggesting dissemination of a resistant
      clone through the food chain.

PMID- 15243025
TI  - Helicobacter pylori antibiotic resistance patterns and genotypes in adult
      dyspeptic patients from a regional population in North Wales.
AB  - OBJECTIVE: Surveillance data on Helicobacter pylori antibiotic susceptibilities
      in Wales are limited, despite resistance being a key factor in treatment failure.
      A single-centre survey was undertaken over 3 years to determine local antibiotic
      resistance rates on isolates from dyspeptic patients in Bangor, Gwynedd (North
      Wales). METHODS: Susceptibilities were determined for 363 isolates by disc
      diffusion and the Etest. Isolates were also genotyped (cagA presence and vacA
      allelic types). RESULTS: Overall in vitro resistance rates were 24% for
      metronidazole and 7% for clarithromycin, with 4% resistant to both antibiotics.
      Resistant strains typically had high MICs of >256 mg/L. Tetracycline resistance
      was identified in only one isolate whereas no isolates showed resistance to
      amoxicillin. There was a two-fold increase in resistance over the study period.
      No gender and age associations with resistance were detected. Resistant and
      susceptible isolates were genotypically diverse with respect to cagA/vacA type
      but the vacA s1m2 form was a feature of all clarithromycin-resistant isolates
      compared with 56% of the susceptible isolates. CONCLUSION: Although the overall
      antibiotic resistance rates of H. pylori from North Wales were low compared with
      many other regions in Europe, continued surveillance, particularly of high-level
      resistance (MIC >256 mg/L), is recommended to monitor the effects of the 'test
      and treat' strategy for H. pylori eradication.

PMID- 15243026
TI  - Anomaly and correlation of killing in the therapeutic properties of silver (I)
      chelation with glutamic and tartaric acids.
AB  - OBJECTIVES: To investigate whether silver chelates or silver ions are more
      effective as therapeutic agents, and to examine their mode of action so that
      safer and stable compounds that have a broad spectrum of therapeutic activities
      can be developed. METHODS: Efficacy was investigated against Pseudomonas
      aeruginosa (ATCC 15442) by determining MIC via a broth macrodilution procedure
      using NCCLS methods for antibiotic susceptibility testing. RESULTS: It was found
      that the responsible agent for silver therapeutic properties is the silver
      chelates rather than silver ions, contradicting previous findings, and the
      efficacy profiles mimic that of free silver ions present in solution.
      CONCLUSIONS: Silver therapeutic activities seem to be more effective as complexes
      an intracellular package-rather than free silver ions, demonstrating that the
      effect of silver is linked to cells' DNA unwinding, and not respiratory or
      membrane functionality as was traditionally recognized.

PMID- 15243027
TI  - Vancomycin-induced deletion of the methicillin resistance gene mecA in
      Staphylococcus aureus.
AB  - OBJECTIVE: To elucidate factors that contribute to the development of vancomycin
      resistance in methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Forty
      nine MRSA isolates were subjected to passage selection with vancomycin to isolate
      mutants with reduced susceptibility to vancomycin. One mutant was chosen for
      detailed molecular and biochemical characterization. RESULTS: Five vancomycin
      resistant mutants (vancomycin MICs, 6-12 mg/L) were obtained in vitro from five
      MRSA parent isolates. Upon acquisition of vancomycin resistance, all mutants
      showed a concomitant decrease in oxacillin resistance. In one particular MRSA
      strain, selection for vancomycin resistance repeatedly produced deletions and
      rearrangements, including loss of the mecA gene. Pleiotropic phenotypical
      changes, such as yellow pigment formation, loss of haemolysis, thickened cell
      wall, increased resistance to lysostaphin and reduced cell wall turnover were
      observed in this mutant. CONCLUSION: Acquisition of vancomycin resistance in one
      MRSA strain triggered mecA deletion suggesting that this deletion, coupled to
      other rearrangements and/or mutations, may be responsible for the increased
      vancomycin resistance phenotype.

PMID- 15243028
TI  - Anti-staphylococcal activity of indolmycin, a potential topical agent for control
      of staphylococcal infections.
AB  - OBJECTIVES: We sought to investigate the anti-staphylococcal activity of
      indolmycin, with particular emphasis on comparing its activity with fusidic acid
      and mupirocin. METHODS: Established procedures were used to examine the activity
      of indolmycin against a range of clinical isolates, including strains resistant
      to fusidic acid and mupirocin. Indolmycin-resistant mutants were recovered and
      characterized phenotypically and genotypically. RESULTS: Indolmycin was
      bacteriostatic and demonstrated good activity against MSSA (methicillin
      susceptible Staphylococcus aureus), MRSA (methicillin-resistant S. aureus) and
      VISA (vancomycin-intermediate S. aureus), including strains resistant to
      mupirocin or fusidic acid. Spontaneous indolmycin-resistant mutants occurred at a
      lower frequency than those selected by mupirocin or fusidic acid and exhibited no
      cross-resistance with the comparative drugs. High-level resistance (indolmycin
      MIC 128 mg/L) that was associated with an H43N mutation in tryptophanyl-tRNA
      synthetase (TrpS), the target enzyme of indolmycin, resulted in loss of bacterial
      fitness. However, the locus responsible for low-level indolmycin resistance
      (indolmycin MICs 8-32 mg/L) was not identified. CONCLUSIONS: Indolmycin is a
      potent anti-staphylococcal agent, which exhibits activity against mupirocin- and
      fusidic acid-resistant strains. Indolmycin might be a candidate for development
      as a topical agent in the treatment of staphylococcal infections and nasal
      carriage of MRSA.

PMID- 15243029
TI  - Mutant prevention concentrations of ciprofloxacin and enrofloxacin for Salmonella
      enterica.
AB  - OBJECTIVES: To determine the mutant prevention concentrations (MPCs) of
      ciprofloxacin and enrofloxacin against four strains of Salmonella enterica
      serovar Enteritidis and four strains of S. Typhimurium including one fully
      susceptible, one multiply resistant (MAR), one GyrA mutant and one GyrA/MAR
      mutant. Further, to examine mutants arising after exposure to sub-MPC
      concentrations of the antibiotics for susceptibility to ciprofloxacin and
      enrofloxacin, and cyclohexane tolerance. METHODS: MICs were determined using the
      agar dilution method of the BSAC. The MPC was recorded as the lowest
      concentration of antibiotic to inhibit growth from an inoculum of 10(10) cfu.
      RESULTS: The MPCs and resulting MPC/MIC ratios of enrofloxacin were generally two
      to four-fold higher than for ciprofloxacin. At 24 h for both antibiotics, MPCs
      were lowest for the fully susceptible strains (0.25-0.5 mg/L), similar for the
      MAR (1-4 mg/L) and GyrA (2-4 mg/L) mutants and highest for the GyrA/MAR mutants
      (1-8 mg/L). MPC/MIC ratios at 24 h were 2-16 for all strains except those for the
      MAR strains without mutation in gyrA where the ratios were 8-64. CONCLUSIONS: The
      ability to eradicate Salmonella in vivo depends on many factors such as
      antibiotic susceptibility of the strain, dose and route of administration. It is
      suggested that these MPC values will be useful when considering dosing
      strategies. In view of the high MPC/MIC ratio, MAR strains with wild-type gyrA,
      although susceptible to ciprofloxacin (MICs 0.06-0.13 mg/L), may give rise to
      treatment failures.

PMID- 15243030
TI  - Inability of L22 ribosomal protein alteration to increase macrolide MICs in the
      absence of efflux mechanism in Haemophilus influenzae HMC-S.
AB  - BACKGROUND: Haemophilus influenzae HMC-C with high-level macrolide resistance
      after multi-step selection by clarithromycin reverted spontaneously and became
      hypersusceptible to macrolides. OBJECTIVE: Determination of macrolide resistance
      mechanism(s) in hypersusceptible and hyperresistant strains. METHODS: The
      presence of macrolide efflux in the strains was studied by radioactive
      erythromycin accumulation. Ribosomal mutations were investigated by sequencing.
      The possible role of acrAB clusters in macrolide resistance was studied by
      sequencing and expression analysis. RESULTS: The parent strain had no ribosomal
      alteration, but both high-level resistant and hypersusceptible strains had R88P
      mutations in ribosomal protein L22. Radioactive macrolide accumulation studies
      pointed to the presence of macrolide efflux in the high-level resistant and
      parent strains, but not in the hypersusceptible derivative. Transformation of
      hypersusceptible strains using total DNA from the parent strain restored the
      macrolide efflux system in the hypersusceptible strain, which was confirmed by
      MIC levels and radioactive erythromycin accumulation similar to that of the
      mutant resistant strain. Analysis of sequence and transcription of acrAB gene
      clusters showed no significant differences between resistant and hypersusceptible
      derivatives. CONCLUSION: Mutation in ribosomal protein L22 alone does not confer
      high-level macrolide resistance unless efflux is present.

PMID- 15243031
TI  - The effect of the beta2-adrenoceptor agonist prodrug BRL-47672 on cardiovascular
      function, skeletal muscle myosin heavy chain, and MyoD expression in the rat.
AB  - The intracellular mechanisms that regulate changes in postnatal myosin heavy
      chain (MHC) expression are not well established. The major objective of this
      study was to examine the acute and chronic effects of administration of BRL
      47672, the prodrug of the beta2-adrenoceptor agonist clenbuterol on MHC and MyoD
      transcription factor expression to determine whether or not changes in MHC
      composition are preceded by changes in MyoD protein expression. To assess to what
      extent the use of BRL-47672 minimized cardiovascular effects, its hemodynamic
      actions were compared with those of clenbuterol. The effect of BRL-47672 on heart
      rate, mean arterial blood pressure, and hindquarters vascular conductance was
      significantly less than that of clenbuterol after a single i.p. injection (250
      microg kg(-1) body mass). In the main study, 4-week old rats were given BRL-47672
      (900 microg kg(-1) body mass) or an equivalent volume of saline (control) daily
      for 1, 28, or 56 days. Soleus muscle (SOL) was excised and MHC and MyoD
      expression analyzed. After 4 weeks, SOL from the BRL-47672-treated animals had
      significantly faster MHC composition (49 +/- 2% MHCIIA) compared with those from
      the control animal (39 +/- 3% MHCIIA, P <0.05). MyoD expression increased by 40%
      after 1 day of BRL-47672 administration (P <0.05) before a change in MHC
      composition. In conclusion, these data suggest that increased expression of fast
      type MHCIIA expression in rat SOL induced by BRL-47672 administration is preceded
      by changes in the level of MyoD transcription factor expression.

PMID- 15243032
TI  - Rapid detection of antimicrobial-resistant organism carriage: an unmet clinical
      need.

PMID- 15243033
TI  - Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid
      protein in sars patients by enzyme-linked immunosorbent assay.
AB  - We report the development of an enzyme-linked immunosorbent assay (ELISA) for the
      detection of severe acute respiratory syndrome (SARS) coronavirus (CoV)
      nucleocapsid protein. The assay was carried out with hyperimmune polyclonal
      nucleocapsid-specific antibodies from guinea pigs and rabbits immunized with
      recombinant His(6)-tagged SARS CoV nucleocapsid protein. The assay was used for
      the detection of SARS CoV nucleocapsid protein in nasopharyngeal aspirate, urine,
      and fecal samples collected from patients with confirmed SARS between days 2 and
      33 after the onset of illness. The ELISA was capable of detecting this protein in
      SARS CoV cell culture lysates at 15 50% tissue culture infective doses/ml but did
      not produce positive signals when tested with cell culture lysates of human
      coronaviruses OC43 and 229E. When tested with 120 nasopharyngeal aspirate, 100
      urine, and 100 fecal specimens from hospitalized patients without SARS, the assay
      was shown to have high specificities-96.7, 99, and 96%, respectively. In an
      evaluation of clinical specimens from SARS patients, 34 (52%) of 66
      nasopharyngeal aspirate samples from 50 patients, 5 (5%) of 94 urine samples from
      94 patients, and 36 (55%) of 65 fecal samples from 65 patients tested positive
      for SARS CoV nucleocapsid protein. Nucleocapsid protein could be detected from
      days 6 to 24 in nasopharyngeal aspirate specimens, from days 11 to 31 in urine
      specimens, and from days 8 to 32 in fecal specimens after the onset of illness.
      Moreover, the protein could be detected in 25 (83%) of 30 nasopharyngeal aspirate
      specimens obtained from days 11 to 15 and in all 7 fecal specimens obtained from
      days 21 to 32. Since the present ELISA is more convenient and economical than
      reverse transcription-PCR, it may serve as an alternative tool for the early
      diagnosis of SARS CoV infection in laboratories with limited resources and
      expertise and for mass screening for the reservoir of SARS CoV. Further studies
      on serial clinical specimens should reveal the duration of nucleocapsid protein
      shedding and may reveal a higher detection rate in SARS patients.

PMID- 15243034
TI  - Reference system for characterization of Bordetella pertussis pulsed-field gel
      electrophoresis profiles.
AB  - Pulsed-field gel electrophoresis (PFGE) has been used as an epidemiological tool
      for surveillance studies of Bordetella pertussis since the early 1990s. To date
      there is no standardized procedure for comparison of results, and therefore it
      has been difficult to directly compare PFGE results between laboratories. We
      propose a profile-based reference system for PFGE characterization of B.
      pertussis strain variation and to establish traceability of B. pertussis PFGE
      results. We initially suggest 35 Swedish reference strains as reference material
      for PFGE traceability. This reference material is deposited at the Culture
      Collection of the University of Gothenburg, Gothenburg, Sweden. Altogether, 1,810
      Swedish clinical isolates from between 1970 and 2003 were studied, together with
      the Swedish Pw vaccine strain, six reference strains, and two U.S. isolates. Our
      system provides evidence that profiles obtained by using only one enzyme, i.e.,
      XbaI, give enough data to analyze the epidemiological relationship between them.
      Characterization with one enzyme is far less labor intensive, yielding results in
      half the time than when a two-enzyme procedure is used. Also, we can see that
      there is a correlation between PFGE profile and pertactin type. One common PFGE
      profile, BpSR11 (n = 455), showed 100% prn2 and 100% Fim3 when analyzed for
      pertactin type and serotype. On the other hand, strains with the same profile may
      express various serotypes when isolated over longer periods of time. Subculturing
      of the same isolate eight times or lyophilization caused no change in PFGE
      profile.

PMID- 15243035
TI  - Bacteremia in an immunocompromised patient caused by a commensal Neisseria
      meningitidis strain harboring the capsule null locus (cnl).
AB  - We recently described the capsule null locus (cnl) of constitutively
      unencapsulated Neisseria meningitidis clonal lineages. cnl meningococci were
      recovered from healthy carriers at high frequency. We here report on the first
      case of invasive disease caused by cnl meningococci in a severely
      immunosuppressed patient with chronic graft-versus-host disease after allogeneic
      peripheral blood stem cell transplantation. The sequence type 845 strain was
      extensively typed and, furthermore, shown to be sensitive to serum bactericidal
      activity.

PMID- 15243036
TI  - Molecular characterization of extended-spectrum beta-lactamases produced by
      clinical isolates of Klebsiella pneumoniae and Escherichia coli from a Korean
      nationwide survey.
AB  - To determine the prevalence and genotypes of extended-spectrum beta-lactamases
      (ESBLs) among clinical isolates of Klebsiella pneumoniae and Escherichia coli, we
      performed antibiotic susceptibility testing, pI determination, induction testing,
      transconjugation, and DNA sequencing analysis. Among the 509 isolates collected
      from 13 university hospitals in Korea, 39.2% produced ESBLs. ESBL-producing
      isolates were detected in every region in Korea. A total of 44.6% of the isolates
      produced both TEM- and SHV-type ESBLs, and 52% of ESBL-producing isolates
      transferred resistance to ceftazidime by transconjugation. The ESBLs were TEM-19,
      TEM-20, TEM-52, SHV-2a, SHV-12, and one new variant identified for the first time
      in Korea, namely, TEM-116. TEM-1 and SHV-12 were by far the most common variants.
      TEM-1, TEM-116, and SHV-12 showed a high prevalence in K. pneumoniae. Two
      isolates (E. coli SH16 and K. pneumoniae SV3) produced CMY-1-like beta
      lactamases, which play a decisive role in resistance to cefoxitin and cefotetan,
      as well as TEM-type enzymes (TEM-20 and TEM-52, respectively). Using MIC patterns
      and DNA sequencing analysis, we postulated a possible evolution scheme among TEM
      type beta-lactamases in Korea: from TEM-1 to TEM-19, from TEM-19 to TEM-20, and
      from TEM-20 to TEM-52.

PMID- 15243037
TI  - Detection of human immunodeficiency virus type 1 antiretroviral resistance
      mutations by high-density DNA probe arrays.
AB  - Genotypic resistance testing has become an important tool in the clinical
      management of patients infected with human immunodeficiency virus type 1 (HIV-1).
      Standard sequencing methodology and hybridization-based technology are the two
      principal methods used for HIV-1 genotyping. This report describes an evaluation
      of a new hybridization-based HIV-1 genotypic test of 99 clinical samples from
      patients infected mostly with HIV-1 subtype B and receiving treatment. This test
      combines RNA extraction with magnetic silica particles, amplification by nested
      reverse transcriptase PCR, and detection with high-density probe arrays designed
      to detect 204 antiretroviral resistance mutations simultaneously in Gag cleavage
      sites, protease, reverse transcriptase, integrase, and gp41. The nested reverse
      transcriptase PCR success rates at viral loads exceeding 1,000 copies/ml were 98%
      for the 2.1-kb amplicon that covers the Gag cleavage sites and the protease and
      reverse transcriptase genes, 92% for the gp41 amplicon, and 100% for the
      integrase amplicon. We analyzed 4,465 relevant codons with the HIV-1 DNA chip
      genotyping assay and the classic sequence-based method. Key resistance mutations
      in protease and reverse transcriptase were identified correctly 95 and 92% of the
      time, respectively. This test should be a valuable alternative to the standard
      sequence-based system for HIV-1 drug resistance monitoring and a useful
      diagnostic tool for simultaneous multiple genetic analyses.

PMID- 15243038
TI  - High-throughput method for detecting genomic-deletion polymorphisms.
AB  - DNA microarrays have been successfully used with different microorganisms,
      including Mycobacterium tuberculosis, to detect genomic deletions relative to a
      reference strain. However, the cost and complexity of the microarray system are
      obstacles to its widespread use in large-scale studies. In order to evaluate the
      extent and role of large sequence polymorphisms (LSPs) or insertion-deletion
      events in bacterial populations, we developed a technique, termed deligotyping,
      which hybridizes multiplex-PCR products to membrane-bound, highly specific
      oligonucleotide probes. The approach has the benefits of being low cost and
      capable of simultaneously interrogating more than 40 bacterial strains for the
      presence of 43 genomic regions. The deletions represented on the membrane were
      selected from previous comparative genomic studies and ongoing microarray
      experiments. Highly specific probes for these deletions were designed and
      attached to a membrane for hybridization with strain-derived targets. The targets
      were generated by multiplex PCR, allowing simultaneous amplifications of 43
      different genomic loci in a single reaction. To validate our approach, 100
      strains that had been analyzed with a high-density microarray were analyzed. The
      membrane accurately detected the deletions identified by the microarray approach,
      with a sensitivity of 99.9% and a specificity of 98.0%. The deligotyping
      technique allows the rapid and reliable screening of large numbers of M.
      tuberculosis isolates for LSPs. This technique can be used to provide insights
      into the epidemiology, genomic evolution, and population structure of M.
      tuberculosis and can be adapted for the study of other organisms.

PMID- 15243039
TI  - Prospective study of a real-time PCR that is highly sensitive, specific, and
      clinically useful for diagnosis of meningococcal disease in children.
AB  - Due to the early administration of antibiotics, meningococcal disease is
      increasingly difficult to diagnose by culturing. Laboratory studies have shown
      PCR to be sensitive and specific, but there have been few clinical studies. The
      objectives of this study were to determine the diagnostic accuracy and clinical
      usefulness of meningococcal PCR through a prospective comparison of real-time
      PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF).
      The setting was a tertiary-care pediatric hospital in Australia, and the
      participants were 118 children admitted with possible septicemia or meningitis.
      The main outcome measures-sensitivity, specificity, and positive and negative
      predictive values-were compared to a "gold standard " fulfilling clinical and
      laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold
      standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was
      positive for 21 (88%), and real-time PCR was positive for 23 (96%). The
      sensitivity, specificity, and positive and negative predictive values of real
      time PCR (the most sensitive test) for all specimens were, respectively, 96% (95%
      confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to 100%), 100%
      (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to
      100%). Of 54 patients with suspected meningococcal disease at admission, 23 had
      positive PCR results. Only one PCR specimen was positive in a patient thought
      unlikely to have meningococcal disease at admission. Blood PCR remained positive
      for 33% of patients tested at up to 72 h. Real-time PCR has high positive and
      negative predictive values in this clinical setting, with better confirmation of
      cases than nested PCR. Targeting patients for PCR based on admission criteria
      appears to be practical, and the test may remain useful for several days after
      the start of antibiotic administration.

PMID- 15243040
TI  - Molecular typing of Neisseria gonorrhoeae isolates by pyrosequencing of highly
      polymorphic segments of the porB gene.
AB  - For prevention and control of gonorrhea, an objective, highly discriminating, and
      reproducible molecular epidemiological characterization of Neisseria gonorrhoeae
      is essential. In the present study, in pursuance of providing such qualities,
      pyrosequencing technology, a fast real-time DNA sequence analysis, was applied to
      six short, highly polymorphic porB gene segments, with subsequent genetic variant
      (genovar) determination of the bacterial isolates. The sequencing templates were
      obtained by real-time PCR amplification, which also included fluorescence melting
      curve analysis of the entire porB gene in order to determine the genogroup
      (porB1a or porB1b allele) prior to pyrosequencing analysis. The PSQ 96 MA system
      used allowed rapid (in approximately 1.5 h) determination of 96 sequences of 20
      to 65 correct nucleotides each. The results were reproducible and mostly in
      concordance with the results of conventional Sanger dideoxy sequencing, with the
      exception of shorter read lengths and some uncertainty in determining the correct
      number of identical nucleotides in homopolymeric segments. The number of sequence
      variants identified in each of the six highly polymorphic segments of the porB1a
      and porB1b alleles (encoding surface-exposed amino acid loops of the mature PorB
      protein) ranged from 5 to 11 and from 8 to 39, respectively. Among porB1a
      isolates (n = 22) and porB1b isolates (n = 65), 22 and 64 unique genovars,
      respectively, were identified. All isolates were typeable. The present results
      provide evidence of a high discriminatory ability, practically the same as that
      for sequencing of the entire porB gene. In conclusion, the fast and high
      throughput pyrosequencing technology can be used for molecular epidemiological
      characterization of N. gonorrhoeae.

PMID- 15243041
TI  - Combination of PCR targeting the VD2 of omp1 and reverse line blot analysis for
      typing of urogenital Chlamydia trachomatis serovars in cervical scrape specimens.
AB  - In this study we developed and evaluated a new PCR-based typing assay, directed
      to the VD2 region of the omp1 gene, for the detection and typing of urogenital
      Chlamydia trachomatis infections. A nested VD2 PCR-reverse line blot (RLB) assay
      was developed for the typing of nine different urogenital serovars of C.
      trachomatis. The assay developed was tested with reference strains of C.
      trachomatis serovars and cervical scrapes of 86 Colombian women previously found
      to be positive for C. trachomatis by using plasmid PCR. Two sets of primers
      directed to the VD2 region of the omp1 gene of C. trachomatis were designed, and
      fragments of 220 and 166 bp were generated in the primary and nested PCRs,
      respectively. In addition, an RLB assay was developed to identify nine different
      urogenital serovars of C. trachomatis (Ba, D, E, F, G, H, I, J, and K) and group
      controls, including group B (Ba, D, and E), group C (I, J, K, and H), and an
      intermediate group (F and G). Using this assay, we were able to type 81 of the 86
      samples (94.2%). Of these samples, 91.3% were single C. trachomatis infections,
      and 8.7% were multiple infections. The most common serovars identified were
      serovars D (22.2%), F (18.5%), G (13.6%), and E (12.3%). Of the women with
      multiple C. trachomatis infections, >50% contained both serovars D and E. The
      nested VD2 PCR-RLB developed is a simple, fast, and specific method for the
      identification of individual urogenital C. trachomatis serovars previously
      detected by using plasmid PCR. Moreover, it is an appropriate method for studying
      multiple C. trachomatis infections and for use in large epidemiological studies.

PMID- 15243042
TI  - Performance of a new, rapid assay for detection of Trichomonas vaginalis.
AB  - Trichomonas vaginalis infection is highly prevalent, may have serious health
      consequence, and is readily treatable. However, screening has been limited by
      currently available tests, which tend to be insensitive, expensive, or require a
      delay before results are reported. The XenoStrip-Tv (Xenotope Diagnostics, Inc.,
      San Antonio, Tex.) was evaluated on vaginal swab specimens from 936 women
      attending sexually transmitted disease clinics in Seattle, Wash. (n = 497), and
      Birmingham, Ala. (n = 439). T. vaginalis prevalence by culture (InPouch; Biomed)
      was 8.7% in Seattle and 21.0% in Birmingham. Compared to culture, the XenoStrip
      assay in Seattle was 76.7% (95% confidence interval [95% CI] = 61.4 to 88.2)
      sensitive and 99.8% (95% CI = 98.8 to 99.9) specific, and in Birmingham it was
      79.4% (95% CI = 69.6 to 87.1) sensitive and 97.1% (95% CI = 94.8 to 98.6)
      specific. The positive predictive values were 97.1% in Seattle and 87.9% in
      Birmingham; the negative predictive values were 97.8 and 94.7%, respectively.
      Rapid test performance did not vary by vaginal symptoms or by the presence of
      other vaginal or cervical syndromes or infections. The sensitivity did vary by
      day of culture-positive result, with a 71% decline in XenoStrip sensitivity for
      every additional day delay until T. vaginalis was first detected in cultures
      (odds ratio = 0.29, 95% CI = 0.18 to 0.49). The rapid assay was more sensitive
      than wet preparation microscopy (78.5% versus 72.4% [P = 0.04]) but was less
      specific (98.6% versus 100% [P = 0.001]). The XenoStrip rapid assay is well
      suited for use in settings with a moderately high prevalence of T. vaginalis
      infection, particularly when microscopy is not practical.

PMID- 15243043
TI  - Risk factors for sporadic cryptosporidiosis among immunocompetent persons in the
      United States from 1999 to 2001.
AB  - Many studies have evaluated the role of Cryptosporidium spp. in outbreaks of
      enteric illness, but few studies have evaluated sporadic cryptosporidiosis in the
      United States. To assess the risk factors for sporadic cryptosporidiosis among
      immunocompetent persons, a matched case-control study was conducted in seven
      sites of the Foodborne Diseases Active Surveillance Network (FoodNet) involving
      282 persons with laboratory-identified cryptosporidiosis and 490 age-matched and
      geographically matched controls. Risk factors included international travel (odds
      ratio [OR] = 7.7; 95% confidence interval [95% CI] = 2.7 to 22.0), contact with
      cattle (OR = 3.5; 95% CI = 1.8 to 6.8), contact with persons >2 to 11 years of
      age with diarrhea (OR = 3.0; 95% CI = 1.5 to 6.2), and freshwater swimming (OR =
      1.9; 95% CI = 1.049 to 3.5). Eating raw vegetables was protective (OR = 0.5; 95%
      CI = 0.3 to 0.7). This study underscores the need for ongoing public health
      education to prevent cryptosporidiosis, particularly among travelers, animal
      handlers, child caregivers, and swimmers, and the need for further assessment of
      the role of raw vegetables in cryptosporidiosis.

PMID- 15243044
TI  - Molecular epidemiology of tuberculosis among immigrants in Hamburg, Germany.
AB  - To study the characteristics of tuberculosis (TB) in foreign-born individuals
      living in Hamburg, Germany, and to discover in what way foreign-born individuals
      contribute to the incidence of TB in Hamburg, an in-depth epidemiological study
      was performed by a combination of classical and molecular methods. In total, 796
      patients with TB were analyzed between 1997 and 2002 (88.7% of all patients with
      culture-positive TB in the study period). Of this total, 334 were foreign-born
      patients from 43 different countries. Of these, only 31 cases were identified as
      a consequence of the screening of 12,176 asylum seekers at entry. Of the foreign
      born patients, 41.9% had been living in Germany for more than 5 years. On the
      basis of the IS6110 typing results for isolates from all patients, 246 patients
      (31%) were classified into 68 clusters, with each cluster containing from 2 to 38
      patients. Among foreign-born individuals, 86 (26%) were represented in 40
      clusters. In multivariate analyses, a previous history as a TB contact had the
      highest predictive risk for clustering among foreign-born patients, followed by
      drug addiction, alcohol dependence, being an asylum seeker, and unemployment.
      Epidemiological links verifying recent transmission could be confirmed for 39 of
      the 86 foreign-born members (45.3%) who formed a cluster, comprising 16 source
      patients and 23 directly infected patients. Of 2,227 previously known contacts of
      foreign-born patients subjected to traditional contact investigation, 14 foreign
      born individuals (0.6%) subsequently contracted culture-confirmed TB, but only 9
      transmissions could be confirmed by IS6110 typing (39.1% of the 23 confirmed
      fresh infections retrospectively confirmed by IS6110 typing). In conclusion, only
      a minority of TB cases among foreign-born individuals are detected by screening
      of asylum seekers or conventional contact tracing. Recent transmission does not
      play an important role in TB among immigrants in Hamburg.

PMID- 15243045
TI  - Performance of commercially available enzyme immunoassays for detection of
      antibodies against herpes simplex virus type 2 in African populations.
AB  - Data are accumulating on the performance of enzyme immunoassays (EIAs) for the
      detection of herpes simplex virus type 2 (HSV-2) infection in North America and
      Europe, but little is known about their performance in other populations. Nine
      test kits were evaluated with 330 serum samples from sub-Saharan Africa. The
      tests were first compared to the monoclonal antibody (MAb) EIA (Central Public
      Health Laboratory, London, United Kingdom). Samples that gave discordant results
      in the MAb EIA and in the three tests that performed best compared to the MAb EIA
      were tested by Western blotting (University of Washington, Seattle). A random
      sample of concordant samples was also tested, and the sensitivities and
      specificities of the different tests were calculated, taking into account this
      sampling strategy. The sensitivities of the tests ranged from 86 to 100%; the
      specificities ranged from 47 to 99%. The tests that performed best were the Gull
      Premier EIA (sensitivity, 86.3%; specificity, 97.6%) and the Kalon Biological
      (sensitivity, 92.3%; specificity, 97.7%) and Biokit (sensitivity, 86.7%;
      specificity, 92.6%) tests. It cannot be assumed that enzyme immunoassays for the
      detection of HSV-2 infection that perform well in industrialized countries will
      perform equally well in other populations.

PMID- 15243046
TI  - Isolation of recombinant antibodies against EspA and intimin of Escherichia coli
      O157:H7.
AB  - Intimin, Tir, and EspA proteins are expressed by attaching-effacing Escherichia
      coli, which include enteropathogenic and enterohemorrhagic E. coli pathotypes.
      EspA proteins are part of the type three secretion system needle complex that
      delivers Tir to the host epithelial cell, while surface arrayed intimin docks the
      bacterium to the translocated Tir. This intimate attachment leads to attaching
      and effacing lesions. Recombinant forms of these effector proteins from
      enterohemorrhagic E. coli O157:H7 were produced by using E. coli expression
      vectors. Binding of intimin and Tir fragments in enzyme-linked immunosorbent
      assay (ELISAs) demonstrated the interaction of intimin fragments containing the C
      terminal 282 or 188 amino acids to a Tir fragment containing amino acid residues
      258 to 361. Recombinant intimin and EspA proteins were used to elicit immune
      responses in rabbits and immune phage-display antibody libraries were produced.
      Screening of these immune libraries by conventional phage-antibody panning and
      colony filter screening produced a panel of antibodies with specificity for EspA
      or intimin. Antibodies recognizing different C-terminal epitopes on intimin bound
      specifically to the gamma intimin of O157:H7 and not to other classes of intimin.
      Antibodies recognizing EspA from E. coli O157 also recognized the protein from
      the eae-deficient O157 mutant DM3 and from E. coli O111. Anti-intimin antibodies
      were also produced as fusion proteins coupled to the reporter molecule alkaline
      phosphatase, allowing the one-step detection of gamma intimin. The isolated
      recombinant monoclonal antibodies were functional in a range of assay formats,
      including ELISA, Western blotting, and dot blots, thus demonstrating their
      diagnostic potential.

PMID- 15243047
TI  - Intra- and interlaboratory study of a method for testing the antifungal
      susceptibilities of dermatophytes.
AB  - The National Committee for Clinical Laboratory Standards (NCCLS) M38-A standard
      for the susceptibility testing of conidium-forming filamentous fungi does not
      explicitly address the testing of dermatophytes. This multicenter study,
      involving six laboratories, investigated the MIC reproducibility of seven
      antifungal agents tested against 25 dermatophyte isolates (5 blinded pairs of
      five dermatophyte species per site for a total of 300 tests), using the method of
      dermatophyte testing developed at the Center for Medical Mycology, Cleveland,
      Ohio. The dermatophytes tested included Trichophyton rubrum, Trichophyton
      mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum
      canis. Seven antifungals with activity against dermatophytes were tested,
      including ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole,
      terbinafine, and voriconazole. Interlaboratory MICs for all isolates were in 92
      to 100% agreement at a visual endpoint reading of 50% inhibition as compared to
      the growth control and 88 to 99% agreement at a visual endpoint reading of 80%
      inhibition as compared to the growth control. Intralaboratory MICs between
      blinded pairs were in 97% agreement at a visual endpoint reading of 50%
      inhibition as compared to the growth control and 96% agreement at a visual
      endpoint reading of 80% inhibition as compared to the growth control. Data from
      this study support consideration of this method as an amendment to the NCCLS M38
      A standard for the testing of dermatophytes.

PMID- 15243048
TI  - Use of robotized DNA isolation and real-time PCR to quantify and identify close
      correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides
      in plasma and cerebrospinal fluid from patients with systemic meningococcal
      disease.
AB  - The present study, using robotized DNA isolation and quantitative PCR based on
      the Neisseria meningitidis-specific capsular transport A gene, demonstrates the
      ease, rapidity, specificity, and sensitivity of quantifying neisserial DNA in
      plasma (n = 65) and cerebrospinal fluid (CSF) (n = 12) from patients with
      systemic meningococcal disease. We found a close correlation between the levels
      of neisserial DNA and lipopolysaccharides in plasma (r = 0.905) and in CSF (r =
      0.964). The median concentration of neisserial DNA in plasma in 23 patients with
      persistent shock was 2 x 10(7) copies/ml, versus <10(3) copies/ml in 42 nonshock
      patients. Furthermore, quantitative PCR made possible estimates of the total
      number of meningococci in plasma, as opposed to conventional blood cultures,
      suggesting about 1,000 dead meningococci for every viable bacterium. Finally,
      with logistic regression analyses, neisserial DNA may predict a patient's disease
      severity and outcome at hospital admission. The number of meningococci in plasma
      and CSF appears to be the main determinant of the lipopolysaccharide levels,
      clinical presentation, and outcome.

PMID- 15243049
TI  - Coexistence of multiple genotypes, including newly identified genotypes, in
      outbreaks of gastroenteritis due to Norovirus in Japan.
AB  - Norovirus (NV) (formerly called Norwalk-like virus) is the most common cause of
      acute nonbacterial gastroenteritis in humans. Recently, we reported an NV
      genotyping scheme based on variability in the capsid N-terminal/shell (N/S)
      domain gene (Katayama et al., Virology 299:225-239, 2002). We found 19 genotypes,
      including nine of genogroup I and 10 of genogroup II. In the present study, we
      investigated the molecular epidemiology of NV from 66 outbreaks that occurred in
      Saitama Prefecture, Japan, from 1997 to 2002. We screened 416 stool specimens by
      a real-time reverse transcription (RT)-PCR method (Kageyama et al., J. Clin.
      Microbiol. 41:1548-1557, 2003) and detected 156 NV-positive specimens, from which
      we amplified the capsid N/S domain gene by RT-PCR and then cloned the PCR
      products. After sequencing these clones, we obtained 368 sequence variants
      (strains). By applying our classification scheme to the strains from Saitama and
      other published strains, we identified a total of 31 genotypes, including an
      additional five genotypes for genogroup I and seven for genogroup II. Of the 31
      genotypes, 26 were present in the Saitama area during that time period. These
      results provide additional evidence for the great diversity of human NV
      genotypes. Specimens from all shellfish-related infections contained multiple
      genotypes, including several new genotypes. On the other hand, single genotypes
      were observed mostly in outbreaks that originated in semiclosed communities.
      Thus, the number of NV genotypes in each outbreak depended on the route of
      transmission.

PMID- 15243050
TI  - Evaluation of the Binax NOW, BD Directigen, and BD Directigen EZ assays for
      detection of respiratory syncytial virus.
AB  - The Binax NOW assay (Binax, Inc., Portland, Maine) and the BD Directigen EZ assay
      (Becton Dickinson and Company, Sparks, Md.), two new rapid immunoassays for
      detection of respiratory syncytial virus (RSV), as well as the BD Directigen RSV
      assay (DRSV) (Becton Dickinson and Company) and direct immunofluorescence
      staining (DFA) were compared with culture for detection of RSV in fresh specimens
      from both children and adults during the 2002-2003 respiratory virus season. The
      majority (95%) of specimens were nasal or nasopharyngeal washes or aspirates. A
      total of 47 (26%) were culture positive for RSV. The overall sensitivities of DFA
      (n = 149), NOW (n = 118), EZ (n = 88), and DRSV (n = 180) compared with culture
      (n = 180) were 93, 89, 59, and 77%, respectively. The specificities of DFA, NOW,
      EZ, and DRSV were 97, 100, 98, and 96%, respectively. However, when results were
      separated into those from children and those from adults, DFA was the only rapid
      test adequate for detection of RSV (sensitivity of 100% compared to 0, 0, and 25%
      for NOW, EZ, and DRSV, respectively) in adults. For children the sensitivities of
      DFA, NOW, EZ, and DRSV were 93, 94, 72, and 81%. The NOW assay was the most
      sensitive and specific and the easiest to perform of the kit tests for detecting
      RSV in children. None of these three rapid kit tests was sensitive for detecting
      RSV in specimens from adults. DFA remains the rapid method of choice for
      detecting RSV in the adult population.

PMID- 15243051
TI  - Assessment of partial sequencing of the 65-kilodalton heat shock protein gene
      (hsp65) for routine identification of Mycobacterium species isolated from
      clinical sources.
AB  - We assessed the ability of an in-house database, consisting of 111 hsp65
      sequences from putative and valid Mycobacterium species or described groups, to
      identify 689 mycobacterial clinical isolates from 35 species or groups. A
      preliminary assessment indicated that hsp65 sequencing confirmed the
      identification of 79.4% of the isolates from the 32 species examined, including
      all Mycobacterium tuberculosis complex isolates, all isolates from 13 other
      species, and 95.6% of all M. avium-M. intracellulare complex isolates.
      Identification discrepancies were most frequently encountered with isolates
      submitted as M. chelonae, M. fortuitum, M. gordonae, M. scrofulaceum, and M.
      terrae. Reexamination of isolates with discrepant identifications confirmed that
      hsp65 identifications were correct in a further 40 isolates. This brought the
      overall agreement between hsp65 sequencing and the other identification methods
      to 85.2%. The remaining 102 isolates had sequence matches below our acceptance
      criterion, had nondifferential sequence matches between two or more species, were
      identified by 16S rRNA sequencing as a putative taxonomic group not contained in
      our database, or were identified by hsp65 and 16S rRNA gene sequencing as a
      species not in our biochemical test database or had conflicting identifications.
      Therefore, to incorporate the unconfirmed isolates it was necessary to create 29
      additional entries in our hsp65 identification database: 18 associated with valid
      species, 7 indicating unique sequences not associated with valid or putative
      species or groups, and 4 associated with unique, but currently described
      taxonomic groups. Confidence in the hsp65 sequence identification of a clinical
      isolate is best when sequence matches of 100% occur, but our data indicate that
      correct identifications can be confidently made when unambiguous matches
      exceeding 97% occur, but are dependent on the completeness of the database. Our
      study indicates that for hsp65 sequencing to be an effective means for
      identifying mycobacteria a comprehensive database must be constructed. hsp65
      sequencing has the advantage of being more rapid and less expensive than
      biochemical test panels, uses a single set of reagents to identify both rapid-
      and slow-growing mycobacteria, and can provide a more definitive identification.

PMID- 15243052
TI  - Dissociation of serum and liver hepatitis C virus RNA levels in patients
      coinfected with human immunodeficiency virus and treated with antiretroviral
      drugs.
AB  - We examined hepatitis C virus (HCV) RNA levels in serum, peripheral blood
      mononuclear cells (PBMC), and the liver for 135 patients with chronic HCV
      infections, 44 of whom were human immunodeficiency virus (HIV) positive and
      treated with highly active antiretroviral therapy (group A), 66 of whom were HIV
      negative (group B), with abnormal serum alanine aminotransferase (ALT) values,
      and 25 of whom were HIV negative, with ALT values of </=1.5 times the normal
      value (group C). Patients had not been treated with interferon, with or without
      ribavirin, at the time of the study. A statistically significant correlation
      between HCV RNA levels in the liver and serum was reproducibly documented,
      whereas this was inconsistent for serum and PBMC. A comparative evaluation of HCV
      RNA levels in the liver and PBMC showed significantly lower values for group A
      than for groups B and C (P < 0.01 and P < 0.0001, respectively). In contrast, HCV
      RNA levels in serum were significantly higher for group A than for group B (P <
      0.001). A dissociation between HCV RNA levels in serum and the liver was found
      for patients with HIV-HCV coinfections. Although the relative contribution of
      extrahepatic reservoirs, including lymphoid cells, to HCV RNA levels in serum is
      unclear, it may be speculated that a low intrahepatic HCV burden is caused by
      restored immunocompetence after successful antiretroviral therapy in coinfected
      patients.

PMID- 15243053
TI  - Measles virus genotyping by nucleotide-specific multiplex PCR.
AB  - A simple genotyping method based on multiplex PCR has been developed to
      discriminate between all active measles virus (MV) clades and genotypes (A, B3.1,
      B3.2, C2, D2-D9, G2-G3, and H1-H2). The sequencing reaction was replaced by six
      multiplex PCRs: one to identify the clade and five to identify the respective
      genotype. Primers were sensitive to clade- and genotype-specific nucleotides and
      generated fragments of type-specific sizes that were analyzed by conventional
      agarose gel electrophoresis. On the basis of all published MV sequences, positive
      and negative predictive values of 99.2% and 98.6% were calculated. Variability in
      the primer binding sites, which could potentially reduce sensitivity, was very
      limited among published sequences. As new genotypes are described, additional
      specific primers can be included in the multiplex PCR with relative ease.
      Although sequencing remains the "gold standard," the present method should
      facilitate MV genotyping especially in developing countries and will therefore
      contribute to enhanced MV control and elimination strategies as recommended by
      the World Health Organization.

PMID- 15243054
TI  - Molecular analysis of the microflora associated with dental caries.
AB  - Molecular techniques have revealed many novel, presumed unculturable, taxa in
      oral infections. The aim of this study was to characterize the bacterial
      community of the middle and advancing front of carious dental lesions by cultural
      and molecular analyses. Samples were collected with a hand excavator from five
      teeth with carious lesions involving dentine. Samples were cultured on blood agar
      and Rogosa agar incubated in air plus 5% CO(2) and on fastidious anaerobe agar
      anaerobically. DNA was also extracted directly from the samples and 16S rRNA
      genes were amplified by PCR with universal primers. PCR products were
      singularized by cloning, and the cloned inserts and cultured isolates were
      identified by 16S rRNA gene sequence analysis. We identified 95 taxa among the
      496 isolates and 1,577 clones sequenced; 44 taxa were detected by the molecular
      method alone; 31 taxa were previously undescribed. Only three taxa, Streptococcus
      mutans, Rothia dentocariosa, and an unnamed Propionibacterium sp., were found in
      all five samples. The predominant taxa by anaerobic cultivation were the novel
      Propionibacterium sp. (18%), Olsenella profusa (14%), and Lactobacillus rhamnosus
      (8%). The predominant taxa in the molecular analysis were Streptococcus mutans
      (16%), Lactobacillus gasseri/johnsonii (13%), and Lactobacillus rhamnosus (8%).
      There was no significant difference between the compositions of the microflora in
      the middle and advancing front samples (P < 0.05, Wilcoxon matched pairs, signed
      ranks test). In conclusion, combined cultural and molecular analyses have shown
      that a diverse bacterial community is found in dentinal caries and that numerous
      novel taxa are present.

PMID- 15243055
TI  - High prevalence of hepatitis C virus type 5 in central France evidenced by a
      prospective study from 1996 to 2002.
AB  - From 1996 to 2002, hepatitis C virus (HCV) typing was prospectively performed for
      1,281 unselected HCV-infected and viremic patients, irrespective of their
      clinical status. Eighty-three patients (6.5%) were coinfected with human
      immunodeficiency virus (HIV) and HCV. A total of 1,195 strains were identified by
      a serotype screening (Murex HCV Serotyping 1-6 assay) and/or genotyping (Inno
      LiPA HCV II) test. The distribution of HCV types showed an unusually high rate of
      type 5 (14.2%) that was stable over time and was the third most frequent type,
      after type 1 (59.1%) and type 3 (15.1%). HCV type 5 was more frequent in patients
      who were older than 50 (P = 10(-6)), but its frequency did not differ
      significantly by gender (P = 0.21). Serotyping was performed for 1,160 strains
      but failed for 30.2% of them. The efficiency depended on HIV status (for HCV-HIV
      coinfected patients, half of the strains were untypeable) and HCV type.
      Genotyping was performed for 428 samples, with an overall efficiency of 99.3%. It
      failed in three cases, which were subsequently identified as HCV type 2.
      Serotyping and genotyping results for 39 patients showed discrepancies between
      the two methods for 4 patients, who had HCV type 2, type 6, or mixed infections.
      Thus, HCV type 5 may also be encountered frequently in Western countries. Its
      apparent confinement to a restricted area raises the question of how it emerged
      and underscores the need for further studies of HCV type prevalence, routes of
      transmission, pathogenicity, and responses to treatment.

PMID- 15243056
TI  - Improved sensitivity of nucleic acid amplification for rapid diagnosis of
      tuberculous meningitis.
AB  - Early diagnosis of tuberculous meningitis (TBM) is essential for a positive
      outcome; but present microbiological diagnostic techniques are insensitive, slow,
      or laborious. We evaluated the standard BDProbeTec ET strand displacement
      amplification method (the standard ProbeTec method) for the detection of
      Mycobacterium tuberculosis complex organisms in parallel with the ProbeTec method
      with a modified pretreatment procedure with 101 prospectively collected
      cerebrospinal fluid specimens from 94 patients with suspected TBM. By the
      modified method, the sample-washing step was omitted. A definitive diagnosis was
      attained by culture. Thirteen specimens from 12 patients were culture positive
      for M. tuberculosis complex organisms; three specimens (23%) were microscopy
      positive for acid-fast bacilli. Among the culture-positive specimens, the
      standard ProbeTec method was positive for 8 (61.5%) and the modified assay was
      positive for 10 (76.9%). The overall specificity by both procedures was 98.8%
      compared to the results of culture. After discrepancy analysis, conducted by
      reviewing the patients' previous laboratory data, the specificity increased to
      100%. If the cutoff value for respiratory specimens was adjusted from the
      recommended value of 3,400 to 1,000, the sensitivity of the modified procedure
      increased to 84.7%, with unchanged specificity. Results were obtained in 3 to 4
      h. The new pretreatment procedure with the ProbeTec assay described here provides
      a rapid, simple, and sensitive tool for the diagnosis of TBM.

PMID- 15243057
TI  - Comparison of three nucleic acid amplification tests for detection of Chlamydia
      trachomatis in urine specimens.
AB  - Traditionally, culture and immunoassays have been performed for the detection of
      sexually transmitted diseases, including Chlamydia trachomatis. However, these
      assays may often require invasive specimen collection methods, such as female
      cervical and male urethral swabs. Recently, nucleic acid amplification tests
      (NAATs) have been approved for testing for the presence of C. trachomatis in
      urine samples. Our objective was to compare the sensitivities and specificities
      of C. trachomatis detection in urine samples with three NAATs: the Abbott LCx
      (LCx), BD ProbeTec ET (ProbeTec), and Gen-Probe APTIMA Combo 2 (AC2). Urine
      specimens (n = 506) were collected from both symptomatic and asymptomatic males
      and females from various high school health clinics. Specimens were tested for C.
      trachomatis with the three NAATs, and a true-positive result was defined as any
      two positive NAATs. The C. trachomatis prevalence was 14.8% (75 of 506 samples).
      Of the 75 urine samples defined as true positives, LCx detected 72, ProbeTec 72,
      and AC2 detected 75. The sensitivities of LCx, ProbeTec, and AC2 for C.
      trachomatis detection were 96.0, 96.0, and 100%, and the specificities were 99.1,
      100, and 98.8%, respectively. Four of five samples that were positive with AC2
      and negative with LCx and ProbeTec were found to be positive with an alternative
      target TMA-based NAAT, APTIMA C. trachomatis, suggesting that they may have been
      true positives. Two of four uniquely positive LCx samples available for
      subsequent testing were both found to be positive by Roche PCR. We found that the
      LCx, ProbeTec, and AC2 NAATs are highly sensitive and specific methods for the
      detection of C. trachomatis in urine specimens and can be recommended for
      noninvasive screening of C. trachomatis in urine.

PMID- 15243058
TI  - Molecular epidemiology of Mycobacterium tuberculosis in western Sweden.
AB  - The genetic diversity of Mycobacterium tuberculosis isolates among patients from
      Sweden was determined by a combination of two PCR-based techniques (spoligotyping
      and variable number of tandem repeats analysis). It resulted in a clustering of
      23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered
      isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing
      (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI;
      6.2%) families. A comparison of the spoligotypes with those in the international
      spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of
      all isolates typed were grouped into six major shared types. A comparison of the
      spoligotypes with those in databases for Scandinavian countries showed that 33%
      of the isolates belonged to an ill-defined T family, followed by the EAI (22%),
      Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families.
      Both the highest number of cases and the proportion of clustered cases were
      observed in patients ages 15 to 39 years. Nearly 10% of the isolates were
      resistant to one or more drugs (essentially limited to isoniazid monoresistance).
      However, none of the strains were multidrug resistant. Data on the geographic
      origins of the patients showed that more than two-thirds of the clustered
      patients with tuberculosis were foreign-born individuals or refugees. These
      results are explained on the basis of both the historical links within specific
      countries and recently imported cases of tuberculosis into Sweden.

PMID- 15243059
TI  - Studies on the involvement of the exopolysaccharide produced by cystic fibrosis
      associated isolates of the Burkholderia cepacia complex in biofilm formation and
      in persistence of respiratory infections.
AB  - Bacteria belonging to the Burkholderia cepacia complex (BCC) are important
      opportunistic pathogens that lead to respiratory infections in patients with
      cystic fibrosis (CF). The clinical outcome following colonization with BCC
      bacteria is highly variable, and so far, unpredictable. A large percentage (80 to
      90%) of BCC isolates from CF patients produce the exopolysaccharide (EPS)
      cepacian, which has been hypothesized to play a role in the colonization and
      persistence of these bacteria in the CF lung. In this work, we demonstrate that
      although it is not required for the initiation of biofilm formation, cepacian
      plays a role in the establishment of thick biofilms. This conclusion was based on
      a comparison of the abilities of EPS-defective mutants derived from a B. cepacia
      mucoid CF isolate by random plasposon insertion mutagenesis and the ability of
      the parental strain to form biofilms. However, the systematic characterization of
      108 CF isolates, corresponding to 15 distinct strains, indicated that other
      strain-dependent factors are also involved in the development of thick, mature
      biofilms. The isolates examined belonged to the species B. cepacia, B.
      multivorans, B. cenocepacia, and B. stabilis and were obtained during a 7-year
      period of surveillance from 21 CF patients receiving care at the major Portuguese
      CF center. Most of them (90%) were serial isolates from 12 persistently infected
      patients. In spite of the concept that bacteria growing in biofilms display more
      resistance to antibiotics and to host phagocyte killing than do planktonically
      growing cells, no clear correlation could be established between the ability of
      the various strains examined to produce EPS and/or to form biofilms in vitro and
      the persistence or virulence of the respiratory infections they caused in
      different patients.

PMID- 15243060
TI  - Highly sensitive assay for detection of enterovirus in clinical specimens by
      reverse transcription-PCR with an armored RNA internal control.
AB  - The objective of the present study was the development of a diagnostic reverse
      transcription (RT)-PCR for the specific detection of enterovirus (EV) RNA in
      clinical specimens controlled by an internal control (IC) RNA. The IC RNA
      contains the same primer binding sites as EV RNA but has a different probe
      region. The IC RNA was packaged into an MS2 phage core particle (armored) and was
      added to the clinical sample to allow monitoring of both extraction efficiency
      and RT-PCR efficiency. Serial dilutions of the IC RNA were made, and the
      detection limit of the RT-PCR was tested in a background of EV RNA-negative
      cerebrospinal fluid. The sensitivity and specificity of the RT-PCR assay were
      tested by using all 64 known EV serotypes, several non-EV serotypes, and two
      Quality Control for Molecular Diagnostics (QCMD) Program EV proficiency panels
      from 2001 and 2002. In total, 322 clinical specimens were tested by RT-PCR, and
      to establish the clinical utility of the RT-PCR, a comparison of the results of
      viral culture and RT-PCR was done with 87 clinical specimens. The lower limit of
      sensitivity was reached at about 150 copies of IC RNA/ml. All 64 EV serotypes
      were positive, while all non-EV serotypes were negative. All culture-positive
      samples of the 2001 QCMD proficiency panel (according to the 50% tissue culture
      infective doses per milliliter) were positive by RT-PCR. Invalid results, i.e.,
      negativity for both EV RNA and IC RNA, due to inhibition of RT-PCR were observed
      for 33.3% of the members of the 2002 QCMD proficiency panel and 3.1% of the
      clinical specimens. Inhibition of RT-PCR could be relieved by the addition of 400
      ng of bovine alpha-casein per microl to both the RT reaction mixture and the PCR
      mixture. With this optimized protocol, the results for all samples of the 2002
      QCMD proficiency panel and all clinical specimens except one fecal sample (0.3%)
      were valid. Evaluation of the clinical samples demonstrated that EV infection
      could be detected in 12 of 87 samples (13.8%) by RT-PCR, while viral culture was
      negative. Our data show that the RT-PCR with armored IC RNA offers a very
      reliable and rapid diagnostic tool for the detection of EV in clinical specimens
      and that the addition of bovine alpha-casein relieved inhibition of the RT-PCR
      for 99.7% of clinical specimens.

PMID- 15243061
TI  - Prevalence of the hifBC, hmw1A, hmw2A, hmwC, and hia Genes in Haemophilus
      influenzae Isolates.
AB  - Adherence of Haemophilus influenzae to respiratory epithelial cells is the first
      step in the pathogenesis of H. influenzae infection and is facilitated by the
      action of several adhesins located on the surface of the bacteria. In this study,
      prevalences of hifBC, which represent the pilus gene cluster; hmw1A, hmw2A, and
      hmwC, which represent high-molecular-weight (HMW) adhesin genes; and hia, which
      represents H. influenzae adhesin (Hia) genes were determined among clinical
      isolates of encapsulated type b (Hib) and nonencapsulated (NTHi) H. influenzae.
      hifBC genes were detected in 109 of 170 (64%) Hib strains and in 46 of 162 (28%)
      NTHi isolates (P = 0.0001) and were more prevalent among the invasive type b
      strains than invasive NTHi strains (P = 0.00003). Furthermore, hifBC genes were
      significantly more prevalent (P = 0.0398) among NTHi throat isolates than NTHi
      middle ear isolates. hmw1A, hmw2A, hmwC, and hia genes were not detected in Hib
      strains. Among NTHi isolates, the prevalence of hmw1A was 51%, the prevalence of
      hmw2A was 23%, the prevalence of hmwC was 48%, and the prevalence of hia was 33%.
      The hmw genes were significantly more prevalent among middle ear than throat
      isolates, while hia did not segregate with a respiratory tract site. These
      results show the variability of the presence of adhesin genes among clinical H.
      influenzae isolates and suggest that hemagglutinating pili may play a larger role
      in H. influenzae nasopharyngeal colonization than in acute otitis media whereas
      the HMW adhesins may be virulence factors for acute otitis media.

PMID- 15243062
TI  - Use of in vivo-generated biofilms from hemodialysis catheters to test the
      efficacy of a novel antimicrobial catheter lock for biofilm eradication in vitro.
AB  - This biofilm study was conducted to assess the in vitro activity of tetrasodium
      EDTA on catheters that had been routinely removed from hemodialysis patients at
      Leeds Teaching Hospitals Trust due to maturation of fistula. Catheters were
      screened by culture of through-catheter flush, and isolates were identified by
      standard methodologies; 20 isolates were found to be biofilm positive. Initial
      biofilm cell count levels averaged above 10(5) CFU/1-cm catheter section.
      Bacteria identified in the biofilms were gram-negative (1 isolate), gram-positive
      (11 isolates), or mixed species (8 isolates). After a 24-h lock, 40 mg of
      tetrasodium EDTA per ml was effective at eradicating the total biofilm viable
      count in almost all cases. The efficacy of tetrasodium EDTA as a catheter lock
      potentially shows that this agent could substantially reduce catheter-related
      infections and be used to treat patients with limited access.

PMID- 15243063
TI  - Widespread dissemination in The Netherlands of the epidemic berlin methicillin
      resistant Staphylococcus aureus clone with low-level resistance to oxacillin.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen
      and represents a growing public health burden due to the emergence and spread of
      epidemic strains, particularly within the hospital environment. An epidemic MRSA
      clone, with characteristic low-level resistance to oxacillin, emerged in the year
      2000 and became endemic in the Netherlands. Multilocus sequence typing
      characterized the strain as sequence type 45, which was previously designated the
      Berlin epidemic MRSA clone. In 2 years, this strain has become the predominant
      MRSA clone in the Netherlands.

PMID- 15243064
TI  - Comparative evaluation of the new version of the INNO-LiPA Mycobacteria and
      genotype Mycobacterium assays for identification of Mycobacterium species from
      MB/BacT liquid cultures artificially inoculated with Mycobacterial strains.
AB  - The performance of two DNA line probe assays, a new version of INNO-LiPA
      Mycobacteria (Innogenetics, Ghent, Belgium) and the GenoType Mycobacterium (Hain
      Diagnostika, Nehren, Germany), were evaluated for identification of mycobacterial
      species isolated from liquid cultures. Both tests are based on a PCR technique
      and designed for simultaneous identification of different mycobacterial species
      by reverse hybridization and line probe technology. The INNO-LiPA Mycobacteria v2
      targeting the 16S-23S rRNA gene spacer region was developed for the simultaneous
      identification of 16 different mycobacterial species. The GenoType Mycobacterium,
      which targets the 23S rRNA gene, allows simultaneous identification of 13
      mycobacterial species. Both tests were evaluated on 110 mycobacterial strains
      belonging to 22 different mycobacterial species (20 reference strains, 83
      clinical strains, and 4 Mycobacterium kansasii strains isolated from tap water)
      that were previously inoculated into MB/BacT bottles. The sensitivity of both
      methods, defined as the number of positive results obtained with the
      Mycobacterium genus probe together with an interpretable result on the number of
      samples tested was 110 of 110 (100%) for INNO-LiPA and 102 of 110 (92.7%) for
      GenoType. For samples with interpretable results, INNO-LiPA was able to correctly
      identify 109 of 110 samples (99.1%), whereas the GenoType correctly identified
      100 of 102 samples (98.0%). Both tests were easy to perform, rapid, and reliable
      when applied to mycobacterial identification directly from MB/BacT bottles.

PMID- 15243065
TI  - Comparison of the APTIMA CT and GC assays with the APTIMA combo 2 assay, the
      Abbott LCx assay, and direct fluorescent-antibody and culture assays for
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae.
AB  - The Gen-Probe APTIMA Combo 2 (AC2) is a Food and Drug Administration-cleared
      nucleic acid amplification test (NAAT) for the detection of Chlamydia trachomatis
      and Neisseria gonorrhoeae from urine and urogenital swab specimens. The Centers
      for Disease Control and Prevention have recommended confirmation of positive NAAT
      results in low-prevalence populations. APTIMA CT (ACT) and APTIMA GC (AGC) are
      two discrete NAATs for C. trachomatis and N. gonorrhoeae detection that are
      suitable for confirming AC2-positive results because they target different
      nucleic acid sequences. Our objective was to determine if ACT and AGC could be
      used as confirmatory tests for AC2 and to correlate the APTIMA assays with
      culture, direct fluorescent-antibody (DFA), and LCx CT and GC assays. Urine and
      swab specimens (1,304) were initially tested with either culture, DFA, or LCx,
      followed by AC2. A subset (675) was then tested with ACT and AGC. There was
      absolute concordance between ACT-AGC and AC2. LCx did not detect 1 of 14 AC2-ACT-
      and 1 of 6 AC2-AGC-positive urine samples, and it yielded one C. trachomatis- and
      one N. gonorrhoeae-positive swab result that were not detected by AC2 and ACT
      AGC. Culture failed to detect 5 of 20 AC2-ACT and 3 of 4 AC2-AGC positives, and
      DFA missed 4 of 4 AC2-ACT positives. Thus, ACT and AGC relative sensitivity
      compared to that of AC2 was 100%. All APTIMA assays detected more confirmed
      positive results than culture, DFA, and LCx. The performance of APTIMA assays was
      not altered by the use of various swab types and by long-term storage of
      specimens. All APTIMA assays are highly sensitive and rapid. ACT and AGC can be
      recommended for confirmation of positive results from other NAATs, such as AC2
      and LCx.

PMID- 15243066
TI  - Endemic, epidemic clone of Salmonella enterica serovar typhi harboring a single
      multidrug-resistant plasmid in Vietnam between 1995 and 2002.
AB  - Salmonella enterica serovar Typhi strains resistant to ampicillin,
      chloramphenicol, tetracyclines, streptomycin, and cotrimoxazole, isolated from
      sporadic cases and minor outbreaks in Vietnam between 1995 and 2002, were typed
      and compared. Plasmid fingerprinting, Vi bacteriophage typing, XbaI pulsed-field
      gel electrophoresis, and PstI ribotyping showed that endemic, epidemic multidrug
      resistant typhoid fever was due, for at least 74.1% of the isolates, to one or
      two clones of serovar Typhi harboring a single resistance plasmid. PstI
      ribotyping was used as a basic technique to ensure that a serovar Typhi expansion
      was clonal.

PMID- 15243067
TI  - Clonal relatedness of enterotoxigenic Escherichia coli strains isolated from a
      cohort of young children in Guinea-Bissau.
AB  - In a cohort study of 200 young children in Guinea-Bissau, it was previously found
      that some enterotoxigenic Escherichia coli (ETEC) strains were more pathogenic
      than others, depending on the type of toxin that they could produce, and that
      natural ETEC infections induced substantial protection against new infections
      with ETEC strains that had the same combination of toxins and colonization
      factors (CFs). We wanted to describe the clonal relatedness of the ETEC strains
      isolated during this study and to investigate whether the protective antigens and
      the virulence factors that were responsible for the pathogenic traits were common
      to strains that were clonally closely related or whether they were more likely to
      be encoded by the ETEC virulence plasmids that normally encode the toxins and the
      CFs. By performing repetitive sequence-based PCR analysis of strains representing
      452 infections, we found that strains that had the same toxin-CF profile were
      usually closely related, although a few were unrelated. Strains that did not have
      the same toxin-CF profiles but that were positive for a given toxin or for a
      given CF were not consistently more closely related to each other than to strains
      that were negative for the same toxin or CF. Our results indicate that the
      pathogenic traits of ETEC were mainly attributed to genes carried on the ETEC
      virulence plasmids. Because most strains that had the same toxin-CF profile were
      closely related, it seems likely that the toxin-CF-specific protection was clonal
      and was not targeting antigens encoded by the virulence plasmids. These results
      are of relevance to the ETEC vaccine development effort.

PMID- 15243069
TI  - Further standardization of broth microdilution methodology for in vitro
      susceptibility testing of caspofungin against Candida species by use of an
      international collection of more than 3,000 clinical isolates.
AB  - The influence of test variables on in vitro susceptibility testing of caspofungin
      was examined with 694 isolates of Candida albicans including seven laboratory
      derived glucan synthesis mutants. The conditions providing the greatest
      separation between the mutant strains and the clinical isolates were RPMI medium,
      MIC end point criterion of partial inhibition, and incubation for 24 h. These
      testing conditions were then applied to 3,322 isolates of Candida spp. (3,314
      clinical isolates and eight glucan synthesis mutants). Among the 11 isolates for
      which caspofungin MICs were >/=2 microg/ml, eight were accounted for by the
      glucan synthesis mutants. The MICs for >99% of isolates were </=1 microg/ml, and
      thus these isolates were differentiated from strains with reduced in vitro and in
      vivo susceptibilities to caspofungin.

PMID- 15243068
TI  - Molecular epidemiology of Serratia marcescens in two hospitals in Gdansk, Poland,
      over a 5-year period.
AB  - The history of the Serratia marcescens population in two hospitals in Danzig,
      Poland, over a 5-year period was analyzed in a study that combined MIC
      evaluation, typing by randomly amplified polymorphic DNA (RAPD) analysis and
      pulsed-field gel electrophoresis, and analysis of extended-spectrum beta
      lactamases (ESBLs). We analyzed 354 isolates collected from 341 patients in two
      teaching hospitals in Danzig, Poland, from 1996 to 2000. The antimicrobial
      susceptibility profiles varied greatly, and for resistance to newer beta-lactams,
      probable AmpC cephalosporinase derepression and ESBL production occurred in about
      23 and 19% of the isolates, respectively. RAPD typing, by which 69 types were
      discerned altogether, revealed a high degree of clonal diversity among the
      populations. However, the four most prevalent types were highly predominant,
      grouping approximately 71% of the isolates studied. These clones were observed in
      the two hospitals and were strong contributors to both outbreaks and the
      background of endemicity of the S. marcescens infections. Some of the strains
      that were not so widely spread (12 RAPD types; approximately 14% of the isolates)
      were responsible for several smaller outbreaks, and the remaining isolates
      represented unique RAPD types (53 types; approximately 15% of the isolates) and
      were probably sporadic introductions from other environments. ESBLs were
      identified in several different clones, and some of these had most likely already
      been introduced into the hospitals as ESBL producers, whereas the others acquired
      the ESBL-encoding genes from other enterobacterial strains in these environments.
      The CTX-M-3 enzyme, which is widely observed in Poland, was the most common ESBL
      type among the S. marcescens isolates, followed by TEM-47 and SHV-5. The complex
      epidemiology of ESBLs, especially in 1999 and 2000, must have arisen from the
      introduction of ESBL producers from other centers, their clonal dissemination,
      and the constant penetration of the S. marcescens populations with plasmids with
      ESBL genes. Multiple S. marcescens isolates were obtained from 11 patients, who
      probably represented both patients with recolonizations and reinfections and
      patients with recurrences of infections with the evolution of the strain's
      susceptibility.

PMID- 15243070
TI  - Simultaneous runs of the Bayer VERSANT HIV-1 version 3.0 and HCV bDNA version 3.0
      quantitative assays on the system 340 platform provide reliable quantitation and
      improved work flow.
AB  - Branched DNA (bDNA) assays to quantify human immunodeficiency virus type 1 (HIV
      1) and hepatitis C virus (HCV) consist of three distinct steps, including sample
      processing, hybridization, and detection, and utilize the System 340 platform for
      plate incubation and washing. Sample processing differs: HIV-1 from 1 ml of
      plasma is concentrated by high-speed centrifugation, whereas HCV plasma or serum
      samples are used without concentration. The first step of hybridization involves
      viral lysis at 63 degrees C: HIV-1 is performed in a heat block, whereas HCV is
      performed in System 340. The remaining hybridization and detection steps are
      similar for HIV-1 and HCV and executed on System 340. In the present study, the
      HIV-1 bDNA assay was adapted for viral lysis in the System 340 platform. The
      adaptation, test method 2, includes a 20-s vortex of concentrated viral pellet
      and lysis working solution, transfer of viral lysate to the 96-well capture
      plate, and transfer to System 340 programmed for HCV assay specifications. With
      test method 2, specificity and quantification were within assay specifications.
      HCV bDNA methodology remains unchanged. Hence, an HIV-1 and an HCV bDNA can be
      run simultaneously on System 340. With simultaneous testing, laboratories can run
      full plates, as well as combinations of full and partial plates. Also,
      simultaneous HIV-1 and HCV bDNA permits labor consolidation and improved workflow
      while maintaining multitasking and rapid patient result turnaround.

PMID- 15243071
TI  - Quantitative analysis of diverse Lactobacillus species present in advanced dental
      caries.
AB  - Our previous analysis of 65 advanced dental caries lesions by traditional culture
      techniques indicated that lactobacilli were numerous in the advancing front of
      the progressive lesion. Production of organic acids by lactobacilli is considered
      to be important in causing decalcification of the dentinal matrix. The present
      study was undertaken to define more precisely the diversity of lactobacilli found
      in this environment and to quantify the major species and phylotypes relative to
      total load of lactobacilli by real-time PCR. Pooled DNA was amplified by PCR with
      Lactobacillus genus-specific primers for subsequent cloning, sequencing, and
      phylogenetic analysis. Based on 16S ribosomal DNA sequence comparisons, 18
      different phylotypes of lactobacilli were detected, including strong
      representation of both novel and gastrointestinal phylotypes. Specific PCR
      primers were designed for nine prominent species, including Lactobacillus
      gasseri, L. ultunensis, L. salivarius, L. rhamnosus, L. casei, L. crispatus, L.
      delbrueckii, L. fermentum, and L. gallinarum. More than three different species
      were identified as being present in most of the dentine samples, confirming the
      widespread distribution and numerical importance of various Lactobacillus spp. in
      carious dentine. Quantification by real-time PCR revealed various proportions of
      the nine species colonizing carious dentine, with higher mean loads of L. gasseri
      and L. ultunensis than of the other prevalent species. The findings provide a
      basis for further characterization of the pathogenicity of Lactobacillus spp. in
      the context of extension of the carious lesion.

PMID- 15243072
TI  - Cross-resistance between fluconazole and ravuconazole and the use of fluconazole
      as a surrogate marker to predict susceptibility and resistance to ravuconazole
      among 12,796 clinical isolates of Candida spp.
AB  - Cross-resistance within a class of antimicrobial agents is a problem that is
      often encountered with antibacterial agents, and it is also an issue with
      antifungal agents. A current example is ravuconazole, a new triazole antifungal
      with an expanded spectrum and potency against Candida spp., Aspergillus spp., and
      other opportunistic fungal pathogens. The present study addresses the issue of
      cross-resistance between fluconazole and ravuconazole and the use of fluconazole
      as a surrogate marker to predict the susceptibility of Candida spp. to
      ravuconazole. Reference broth microdilution MIC results for 12,796 strains of
      Candida spp. isolated from more than 200 medical centers worldwide were used.
      Ravuconazole MICs and tentative interpretive categories (susceptible, </=1
      microg/ml; resistant, >/=2 microg/ml) were compared with those of fluconazole by
      using regression statistics and error rate bounding analyses. For all 12,796
      isolates, the absolute categorical agreement rate was 92.5% (rate of false
      susceptible results, or very major errors [VME], 0.1%). Ravuconazole was active
      (MIC, </=1 microg/ml) against 99.9% of the fluconazole-susceptible isolates, 96%
      of the fluconazole-susceptible dose-dependent isolates, and 49% of the
      fluconazole-resistant isolates, including 99% of the Candida krusei isolates.
      Since ravuconazole is 16- to 32-fold more potent than fluconazole, the
      performance of fluconazole as a surrogate marker for ravuconazole susceptibility
      was improved by designating those isolates with fluconazole MICs of </=32
      microg/ml susceptible to ravuconazole, resulting in a categorical agreement rate
      of 98.3%, with a VME rate of 0.3% (99 and 0.4%, respectively, when C. krusei was
      omitted). Cross-resistance between fluconazole and ravuconazole applies most
      directly to fluconazole-resistant Candida glabrata and is variable among other
      species of Candida. Fluconazole may serve as a surrogate marker to predict the
      susceptibility of Candida spp. to ravuconazole.

PMID- 15243073
TI  - Geographic variation in the susceptibilities of invasive isolates of Candida
      glabrata to seven systemically active antifungal agents: a global assessment from
      the ARTEMIS Antifungal Surveillance Program conducted in 2001 and 2002.
AB  - We examined the susceptibilities to amphotericin B, flucytosine, fluconazole,
      posaconazole, ravuconazole, voriconazole, and caspofungin of 601 invasive
      isolates of Candida glabrata and grouped the isolates by geographic location:
      North America (331 isolates), Latin America (58 isolates), Europe (135 isolates),
      and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested
      are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at
      a MIC of </=1 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml; 99.2% S) were
      the most active agents in all geographic regions. Fluconazole susceptibility was
      highest in the Asia-Pacific region (80.5% S, 3.9% resistant [R]) and lowest in
      North America (64% S, 10.3% R) and Latin America (62.1% S, 3.4% R). The extended
      spectrum triazoles were most active in the Asia-Pacific region (90 to 96.1% S)
      and least active in North America (82.5 to 90.3% S). All 46 isolates that were
      resistant to fluconazole were susceptible to caspofungin (MIC(90), 0.06
      microg/ml) and flucytosine (MIC(90), 0.12 microg/ml) and exhibited variable cross
      resistance to posaconazole, ravuconazole, and voriconazole.

PMID- 15243074
TI  - Evaluation of the Hyplex BloodScreen Multiplex PCR-Enzyme-linked immunosorbent
      assay system for direct identification of gram-positive cocci and gram-negative
      bacilli from positive blood cultures.
AB  - We evaluated the Hyplex BloodScreen PCR-enzyme-linked immunosorbent assay (ELISA)
      system (BAG, Lich, Germany), a new diagnostic test for the direct identification
      of gram-negative bacilli and gram-positive cocci from positive blood cultures,
      with 482 positive BACTEC 9240 blood culture bottles. The test involves
      amplification of the bacterial DNA by multiplex PCR and subsequent hybridization
      of the PCR product to specific oligonucleotide probes in an ELISA-based format.
      The available probes allow the separate detection of Escherichia coli,
      Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella spp., Staphylococcus
      aureus, Staphylococcus epidermidis, Enterococcus faecalis/Enterococcus faecium,
      Streptococcus pyogenes, and Streptococcus pneumoniae and the staphylococcal mecA
      gene. The Hyplex BloodScreen test showed an overall sensitivity of 100% for the
      identification of gram-negative bacilli and 96.6 to 100% for the identification
      of gram-positive cocci (S. aureus, 100%; S. epidermidis, 97.2%; Enterococcus
      faecalis/Enterococcus faecium, 96.6%; and Streptococcus pneumoniae, 100%). The
      specificities of the test modules ranged from 92.5 to 100% for gram-negative
      bacilli and 97.7 to 100% for gram-positive cocci (Escherichia coli, 92.5%;
      Pseudomonas aeruginosa, 98.5%; Klebsiella spp., 100%; Enterobacter aerogenes,
      100%; S. aureus, 100%, S. epidermidis, 97.7%; Enterococcus faecalis/Enterococcus
      faecium, 99.6%; Streptococcus pyogenes, 100%; and Streptococcus pneumoniae,
      99.3%). The result of the mecA gene detection module correlated with the result
      of the phenotypic oxacillin resistance testing in all 38 isolates of
      Staphylococcus aureus investigated. In conclusion, the Hyplex BloodScreen PCR
      ELISA system is well suited for the direct and specific identification of the
      most common pathogenic bacteria and the direct detection of the mecA gene of
      Staphylococcus aureus in positive blood cultures.

PMID- 15243075
TI  - Molecular and ultrastructural characterization of porcine hippurate-negative
      Brachyspira pilosicoli.
AB  - Brachyspira pilosicoli, the causative agent of porcine intestinal spirochetosis,
      usually has hippurate-cleaving capacity. We have regularly isolated hippurate
      negative B. pilosicoli from cases of porcine diarrhea. In this study, we show
      that these biochemically atypical B. pilosicoli isolates can be classified as B.
      pilosicoli. 16S ribosomal DNA was partially sequenced from eight hippurate
      negative and two hippurate-positive B. pilosicoli-like isolates from seven herds.
      The differences in nucleotide sequence with B. pilosicoli P43/6/78 type strain
      were not associated with hippurate cleavage. In 877 bp, the hippurate-negative
      isolates had a similarity of 98.63 to 100% to the type strain, with the
      corresponding figures for the two hippurate-positive isolates being 98.86 and
      100%. The nucleotide sequences of hippurate-positive isolates were identical to
      the respective sequences of hippurate-negative isolates from one herd. The DNA
      macrorestriction patterns of a total of 20 hippurate-negative and -positive B.
      pilosicoli isolates were diverse, and no clustering in conjunction with the
      hippurate reaction was found. In two herds, hippurate-positive and -negative B.
      pilosicoli isolates had a common macrorestriction pattern. The ultrastructure of
      hippurate-negative isolates was similar to the type strain. In conclusion, B.
      pilosicoli can be either hippurate positive or negative and, thus, the scheme for
      biochemical differentiation of porcine Brachyspira should be revised to include
      identification of hippurate-negative B. pilosicoli.

PMID- 15243076
TI  - Comparison of different methods of isolation of DNA of commonly encountered
      Candida species and its quantitation by using a real-time PCR-based assay.
AB  - Molecular diagnosis based on genomic amplification methods such as real-time PCR
      assay has been reported as an alternative to conventional culture for early
      detection of invasive candidiasis. However, a major limitation of the molecular
      method is the difficulty associated with breaking fungal cell walls since the DNA
      extraction step still requires more than half of a working day. It has been
      suggested that PCR detection of free template DNA in serum is preferred over the
      use of whole blood for the diagnosis of systemic candidiasis. In this study, two
      conventional procedures (the first [the HLGT method] consists of boiling sera in
      an alkaline guanidine-phenol-Tris reagent, and the second [the PKPC method] uses
      proteinase K digestion, followed by organic extraction) and three commercially
      available kits for DNA isolation were evaluated for sensitivity, purity, cost,
      and use of template for most clinically important Candida species in a TaqMan
      based PCR assay. To optimize these procedures, we evaluated the effect of adding
      0.5% bovine serum albumin to DNA extracts and found that it decreased the effects
      of inhibitors. The QIAamp DNA blood kit did significantly shorten the duration of
      the DNA isolation but was among the most expensive procedures. Furthermore, the
      QIAamp DNA blood kit proved to be as sensitive as the HLGT DNA isolation method
      for PCR amplification from 52 serum samples from hematology or oncology patients
      with clinically proven or suspected systemic Candida infections. All PCR-positive
      samples showed approximately the same Candida species load by both procedures
      (100% correspondence), whereas one discordant result was obtained between PCR and
      blood culture.

PMID- 15243077
TI  - Multiplex real-time PCR for detection of anaplasma phagocytophilum and Borrelia
      burgdorferi.
AB  - A multiplex real-time PCR assay was developed for the simultaneous detection of
      Anaplasma phagocytophilum and Borrelia burgdorferi. The assay was tested on
      various Anaplasma, Borrelia, Erhlichia, and Rickettsia species, as well as on
      Bartonella henselae and Escherichia coli, and the assay was found to be highly
      specific for A. phagocytophilum and the Borrelia species tested (B. burgdorferi,
      B. parkeri, B. andersonii, and B. bissettii). The analytical sensitivity of the
      assay is comparable to that of previously described nested PCR assays (A.
      phagocytophilum, 16S rRNA; B. burgdorferi, fla gene), amplifying the equivalent
      of one-eighth of an A. phagocytophilum-infected cell and 50 borrelia spirochetes.
      The dynamic range of the assay for both A. phagocytophilum and B. burgdorferi was
      >/=4 logs of magnitude. Purified DNA from A. phagocytophilum and B. burgdorferi
      was spiked into DNA extracted from uninfected ticks and from negative control
      mouse and human bloods, and these background DNAs were shown to have no
      significant effect on sensitivity or specificity of the assay. The assay was
      tested on field-collected Ixodes scapularis ticks and shown to have 100%
      concordance compared to previously described non-probe-based PCR assays. To our
      knowledge, this is the first report of a real-time multiplex PCR assay that can
      be used for the simultaneous and rapid screening of samples for A.
      phagocytophilum and Borrelia species, two of the most common tick-borne
      infectious agents in the United States.

PMID- 15243078
TI  - Multiplex PCR assay for detection of Streptococcus suis species and serotypes 2
      and 1/2 in tonsils of live and dead pigs.
AB  - A PCR assay was developed for the detection of Streptococcus suis serotypes 2 and
      1/2. This multiplex PCR is based on the amplification of the gene coding for 16S
      rRNA of S. suis and on the amplification of the cps2J gene coding for the capsule
      of S. suis serotypes 2 and 1/2. An internal control was constructed and added in
      this test to monitor the efficiency of amplification in each reaction. To
      evaluate the specificity of the test, 31 strains of other bacterial species
      related to S. suis or isolated from pigs and 42 strains of S. suis serotypes 1
      and 3 to 34 were analyzed. The detection threshold of the test was 28 S. suis
      CFU/ml. The specificity and the sensitivity of the multiplex PCR test and the
      presence of an internal control allowed the analysis of biological samples
      without a culture step. The PCR assay was then applied to the detection of 14 S.
      suis serotype 1/2 strains, 88 S. suis serotype 2 strains isolated from pigs, and
      25 S. suis serotype 2 strains isolated from humans. This test was also applied to
      analyze tonsil samples of pigs experimentally infected and carrier pigs without
      any symptoms.

PMID- 15243079
TI  - Detection and typing of human papillomavirus by e6 nested multiplex PCR.
AB  - A nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus
      primers and type-specific primers was evaluated for the detection and typing of
      human papillomavirus (HPV) genotypes 6/11, 16, 18, 31, 33, 35, 39, 42, 43, 44,
      45, 51, 52, 56, 58, 59, 66, and 68 using HPV DNA-containing plasmids and cervical
      scrapes (n = 1,525). The performance of the NMPCR assay relative to that of
      conventional PCR with MY09-MY11 and GP5+-GP6+ primers, and nested PCR with these
      two primer sets (MY/GP) was evaluated in 495 cervical scrapes with corresponding
      histologic and cytologic findings. HPV prevalence rates determined with the NMPCR
      assay were 34.7% (102 of 294) in the absence of cervical intraepithelial
      neoplasia (CIN 0), 94.2% (113 of 120) in the presence of mild or moderate
      dysplasia (CIN I/II), and 97.8% (44 of 45) in the presence of severe dysplasia
      (CIN III). The combination of all four HPV detection methods applied in the study
      was taken as "gold standard": in all three morphological subgroups the NMPCR
      assay had significantly (P < 0.0001) higher sensitivities than the MY09-MY11 and
      GP5+-GP6+ assays and sensitivities comparable or equal to those of the MY/GP
      assay. All 18 HPV genotypes investigated were detected among the clinical
      samples. The ratio of high- to low-risk HPV genotypes increased from 4:1 (80 of
      103) in CIN 0 to 19:1 (149 of 157) in CIN I to III. Multiple infections were
      detected in 47.9% (124 of 259) of the patients. In conclusion, the novel NMPCR
      method is a sensitive and useful tool for HPV DNA detection, especially when
      exact HPV genotyping and the identification of multiple HPV infections are
      required.

PMID- 15243080
TI  - Diversity among community isolates of methicillin-resistant Staphylococcus aureus
      in Australia.
AB  - Community methicillin-resistant Staphylococcus aureus (CMRSA) strains are being
      isolated with increasing frequency around the world. In Western Australia CMRSA
      are endemic in geographically remote communities and have been found to belong to
      five different contour-clamped homogeneous electric field (CHEF) electrophoretic
      patterns. Representatives of each of these CHEF patterns have been compared to
      CMRSA representative of CHEF patterns from other Australian states and New
      Zealand. With one exception, all of the isolates were nonmultiresistant and were
      not resistant to many antimicrobial agents other than the beta-lactams. With one
      exception, which is not believed to be a CMRSA, all of the isolates harbored a
      beta-lactamase plasmid. Erythromycin resistance was associated with a 2-kb
      plasmid. One of the beta-lactamase plasmids was found to be able to acquire
      additional resistance determinants to become a multiple resistance plasmid. There
      were 10 multilocus sequence types belonging to eight distantly related clonal
      complexes of S. aureus. One new sequence type was found. Although most of the
      CMRSA harbored the type IVa SCCmec, a type IV structural variant was found and
      two new SCCmec types were identified. Protein A gene (spa) typing revealed two
      new spa types and, with two exceptions, corresponded to multilocus sequence
      typing. In contrast to other reports on CMRSA, most of the CMRSA strains studied
      here did not contain the Panton-Valentine leukocidin genes. The results also
      demonstrate that nonmultiresistant hospital strains such as UK EMRSA-15 may be
      able to circulate in the community and could be mistaken for CMRSA based on their
      resistance profiles.

PMID- 15243081
TI  - Comparison of three commercially available serologic assays used to detect human
      parvovirus B19-specific immunoglobulin M (IgM) and IgG antibodies in sera of
      pregnant women.
AB  - A split-sample study was conducted to evaluate the performances of three enzyme
      immunoassays (EIAs) utilizing one or more conformational antigens to detect human
      parvovirus B19 (B19V)-specific immunoglobulin M (IgM) or IgG in the sera of 198
      pregnant women. We compared EIAs available from Biotrin International, Inc.
      (Dublin, Ireland), Medac Diagnostika (Wedel, Germany), and Mikrogen (Martinsried,
      Germany). Specimens with discordant results were analyzed further using an
      immunofluorescence assay (Biotrin). Equivocal data accounted for close to half of
      all the discrepant results for both IgM and IgG, with 7 of 15 discrepant results
      from the Medac and Mikrogen kits involving equivocal data and the Biotrin kit
      giving a single equivocal result. For each specimen, a consensus was established
      from the four test results if agreement occurred among at least three of four
      results. Overall, the highest percentage of agreement with the consensus results
      was seen when Biotrin kits were used; 194 (100%) of 194 and 194 (99.5%) of 195
      results for IgM and IgG, respectively, agreed with the consensus results. When
      Medac kits were used, 189 (97.4%) of 194 and 191 (97.9%) of 195 results for IgM
      and IgG, respectively, agreed with the consensus, and when Mikrogen kits were
      used, 179 (92.3%) of 194 and 193 (99%) of 195 results for IgM and IgG,
      respectively, agreed with the consensus. Given the consensus results, the Medac
      EIA appeared to generate presumed false-positive results for IgM and the Mikrogen
      EIA appeared to generate presumed false-positive results for IgG and IgM. In
      summary, the Biotrin EIAs produced far fewer equivocal results than the other
      assays and results of the Biotrin EIAs agreed more often with the consensus
      results than did those of the other commercially available EIAs for detecting
      B19V-specific IgM and IgG antibodies.

PMID- 15243082
TI  - Discovery of novel human and animal cells infected by the severe acute
      respiratory syndrome coronavirus by replication-specific multiplex reverse
      transcription-PCR.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative
      agent of the recent outbreak of severe acute respiratory syndrome. VeroE6 cells,
      fetal rhesus monkey kidney cells, and human peripheral blood mononuclear cells
      were the only cells known to be susceptible to SARS-CoV. We developed a multiplex
      reverse transcription-PCR assay to analyze the susceptibility of cells derived
      from a variety of tissues and species to SARS-CoV. Additionally, productive
      infection was determined by titration of cellular supernatants. Cells derived
      from three species of monkey were susceptible to SARS-CoV. However, the levels of
      SARS-CoV produced differed by 4 log(10). Mink lung epithelial cells (Mv1Lu) and R
      Mix, a mixed monolayer of human lung-derived cells (A549) and mink lung-derived
      cells (Mv1Lu), are used by diagnostic laboratories to detect respiratory viruses
      (e.g., influenza virus); they were also infected with SARS-CoV, indicating that
      the practices of diagnostic laboratories should be examined to ensure appropriate
      biosafety precautions. Mv1Lu cells produce little SARS-CoV compared to that
      produced by VeroE6 cells, which indicates that they are a safer alternative for
      SARS-CoV diagnostics. Evaluation of cells permissive to other coronaviruses
      indicated that these cell types are not infected by SARS-CoV, providing
      additional evidence that SARS-CoV binds an alternative receptor. Analysis of
      human cells derived from lung, kidney, liver, and intestine led to the discovery
      that human cell lines were productively infected by SARS-CoV. This study
      identifies new cell lines that may be used for SARS-CoV diagnostics and/or basic
      research. Our data and other in vivo studies indicate that SARS-CoV has a wide
      host range, suggesting that the cellular receptor(s) utilized by SARS-CoV is
      highly conserved and is expressed by a variety of tissues.

PMID- 15243083
TI  - Use of swabs without transport media for the Gen-Probe Group A Strep Direct Test.
AB  - For several years we used rayon or Dacron swabs with liquid transport media for
      collection and transport of throat swab specimens for testing with the Gen-Probe
      Group A Strep Direct Test (GASDT). A report of favorable results with a Dacron
      swab without any transport media for GASDT by another laboratory prompted us to
      compare detection of group A streptococci (GAS) with and without transport media
      (referred to as "wet" and "dry" swabs, respectively). Phase one of this study
      used swabs seeded with GAS. Initially, six recent clinical isolates of GAS were
      inoculated onto wet and dry swabs and stored at room temperature (RT). After 1,
      2, and 3 days of storage, colony counting and GASDT were performed with the
      swabs. The results, expressed as the mean percentage of the results at zero time,
      were as follows: for GASDT with wet swabs at 1, 2, and 3 days, 62, 51, and 56%,
      respectively; for GASDT with dry swabs at 1, 2, and 3 days, 105, 80, and 85%,
      respectively; for colony counts with wet swabs at 1, 2, and 3 days, 52, 26, and
      13%, respectively; for colony counts with dry swabs at 1, 2, and 3 days, 10, 0,
      and 0%, respectively. An additional six strains of GAS were tested in a similar
      manner, except that extracts of pharyngeal flora (PF) were added to the inocula.
      The results obtained with extracts of PF were comparable to those obtained with
      GAS alone. We also compared the performance of GASDT with wet and dry swabs
      stored at RT and 4 degrees C. Ten strains of GAS were inoculated onto wet and dry
      swabs, and GASDT was performed each day for 9 days. The GASDT results for swabs
      on day 9, expressed as the mean percentage of the results obtained at zero time,
      were as follows: dry swab and 4 degrees C, 59%; wet swab and 4 degrees C, 31%;
      dry swab and RT, 33%; and wet swab and RT, 19%. In phase two of this study we
      conducted a clinical evaluation to determine whether the differences observed
      with seeded specimens would also be evident with patient specimens. We used a
      single dry Dacron swab paired with a single rayon Bacti-Swab with liquid Stuart
      transport medium for the clinical evaluation. Specimens were collected from 1,005
      outpatients, plated onto a Strep Selective Agar plate, and then tested within 30
      min by GASDT. If culture of GAS from the same swab is used to define a true
      positive test result, the sensitivities and specificities were as follows: GASDT
      with wet swabs, 86.2 and 98.5%, respectively; GASDT with dry swabs, 90.7 and
      98.1%, respectively. However, the use of culture as the "gold standard" may
      understate the actual performance characteristics of GASDT, particularly for the
      dry swabs. In conclusion, for GASDT the use of swabs without transport media may
      be preferable to the use of swabs with transport media.

PMID- 15243084
TI  - Amplicon sequencing and improved detection of human rhinovirus in respiratory
      samples.
AB  - Improved knowledge of the genotypic characteristics of human rhinovirus (HRV) is
      required, as are nucleic detection assays with the capacity to overcome both the
      similarities between members of the family Picornaviridae and the wide diversity
      of different HRV serotypes. The goal of the present study was to investigate the
      variability and the genotypic diversity of clinical strains circulating in the
      community. Since most reverse transcription (RT)-PCR assays available cannot
      differentiate HRV from other members of the family Picornaviridae, we also
      validated an assay specific for HRV detection. The 5' noncoding regions of 87
      different HRV serotypes and clinical isolates were sequenced. On the basis of
      sequence analysis and phylogenetic determination, we first confirmed that all
      clinical isolates were HRV. We then validated a real-time RT-PCR assay that was
      able not only to detect all HRV serotypes and all clinical isolates tested but
      also to accurately discriminate between rhinovirus and other viruses from the
      family Picornaviridae. This assay was negative with isolates of coxsackievirus
      (types A and B), echovirus, enterovirus, parechovirus, and poliovirus, as well as
      nonpicornaviruses. Among a series of bronchoalveolar lavage specimens, 4% (7 of
      161) were positive by culture, whereas 13% (21 of 161) were positive by RT-PCR.
      In the present study we showed that to specifically identify HRV in clinical
      specimens, diagnostic assays need to overcome both the diversities and the
      similarities of picornaviruses. By sequencing the 5' noncoding regions of
      rhinoviruses recovered from clinical specimens, we designed probes that could
      specifically detect rhinovirus.

PMID- 15243085
TI  - Immunohistostaining assays for detection of Chlamydia pneumoniae in
      atherosclerotic arteries indicate cross-reactions with nonchlamydial plaque
      constituents.
AB  - Detection of Chlamydia pneumoniae antigens in PCR-negative atheromata by
      immunohistochemistry assays has given rise to controversies regarding a link
      between the bacterium and atherosclerosis. One hundred ninety-seven human
      arterial segments removed surgically were examined for C. pneumoniae DNA by
      conventional PCR with three different primer pairs and by real-time PCR in two
      different laboratories. No C. pneumoniae DNA was detected. Eighty atherosclerotic
      lesions were studied by immunohistochemistry assays. Immunoreactivity for C.
      pneumoniae was frequently present but was not related to the extent of
      atherosclerosis. Mammary arteries showed immunoreactivity. Serial sections of 17
      atheromata were analyzed by Western blotting, histological staining, and UV
      fluorescence microscopy. Chlamydial proteins were not detected. The sites with
      positive results by C. pneumoniae immunohistostaining assays precisely matched
      the sites with autofluorescent ceroid deposits. Immunoblotting and antigenic
      staining for C. pneumoniae were negative in tests with fetal aortas. The absence
      of C. pneumoniae DNA in human atherosclerotic lesions, together with negative
      results for C. pneumoniae proteins by Western blotting analysis, and the perfect
      matching of C. pneumoniae immunoreactive sites with sites with autofluorescent
      ceroid deposits suggest a nonspecific reactivity of antichlamydial antibodies
      with plaque constituents. On the basis of the results of the present study, there
      are no arguments for an etiologic role of C. pneumoniae in atherosclerosis.

PMID- 15243087
TI  - Use of oligonucleotide microarrays for rapid detection and serotyping of acute
      respiratory disease-associated adenoviruses.
AB  - The cessation of the adenovirus vaccination program for military trainees has
      resulted in several recent acute respiratory disease (ARD) outbreaks. In the
      absence of vaccination, rapid detection methods are necessary for the timely
      implementation of measures to prevent adenovirus transmission within military
      training facilities. To this end, we have combined a fluorogenic real-time
      multiplex PCR assay with four sets of degenerate PCR primers that target the E1A,
      fiber, and hexon genes with a long oligonucleotide microarray capable of
      identifying the most common adenovirus serotypes associated with adult
      respiratory tract infections (serotypes 3, 4, 7, 16, and 21) and a representative
      member of adenovirus subgroup C (serotype 6) that is a common cause of childhood
      ARD and that often persists into adulthood. Analyses with prototype strains
      demonstrated unique hybridization patterns for representative members of
      adenovirus subgroups B(1), B(2), C, and E, thus allowing serotype determination.
      Microarray-based sensitivity assessments revealed lower detection limits (between
      1 and 100 genomic copies) for adenovirus serotype 4 (Ad4) and Ad7 cell culture
      lysates, clinical nasal washes, and throat swabs and purified DNA from clinical
      samples. When adenovirus was detected from coded clinical samples, the results
      obtained by this approach demonstrated an excellent concordance with those
      obtained by the more established method of adenovirus identification as well as
      by cell culture with fluorescent-antibody staining. Finally, the utility of this
      method was further supported by its ability to detect adenoviral coinfections,
      contamination, and, potentially, recombination events. Taken together, the
      results demonstrate the usefulness of the simple and rapid diagnostic method
      developed for the unequivocal identification of ARD-associated adenoviral
      serotypes from laboratory or clinical samples that can be completed in 1.5 to 4.0
      h.

PMID- 15243086
TI  - Antigenic evidence of prevalence and diversity of Mycobacterium tuberculosis
      arabinomannan.
AB  - Arabinomannan (AM) is a polysaccharide of the mycobacterial capsule. The capsular
      polysaccharides of various microorganisms are diverse, and this diversity is
      important for classification of organisms into serotypes and vaccine development.
      In the present study we examined the prevalence and diversity of AM among
      Mycobacterium tuberculosis strains using four AM-binding monoclonal antibodies
      (MAbs). One of these MAbs, MAb 9d8, is known to bind to AM specifically. By whole
      cell enzyme-linked immunosorbent assay (ELISA), the AM recognized by MAb 9d8 was
      detected on the surfaces of 9 of 11 strains, while 2 strains showed no reactivity
      with MAb 9d8. However, the AM recognized by MAb 9d8 was found in the culture
      supernatants of all 11 M. tuberculosis strains tested, as demonstrated by capture
      ELISA. Other AM-binding MAbs reacted both with the surfaces and with the culture
      supernatants of all 11 strains. Mice immunized with an experimental AM
      recombinant Pseudomonas aeruginosa exoprotein A (rEPA) conjugate vaccine had an
      increased antibody response to AM and a moderate reduction in the numbers of CFU
      in their organs 7 days after challenge. Our results indicate that AM was detected
      in all M. tuberculosis strains tested, with differences in epitope distributions
      of certain strains. In addition, our results suggest that an experimental AM-rEPA
      vaccine has a moderate effect on the numbers of CFU in organs early after
      infection.

PMID- 15243088
TI  - Molecular genotyping of a large, multicentric collection of tubercle bacilli
      indicates geographical partitioning of strain variation and has implications for
      global epidemiology of Mycobacterium tuberculosis.
AB  - Tuberculosis continues to be a major killer disease, despite an all-out effort
      launched against it in the postgenomic era. We describe here the population
      structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide
      scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more
      than 1,100 independent isolates from 11 different countries. The bacterial
      strains were genotyped based on a total of 136 +/- 1 different FAFLP markers at
      the genome sequence interface, with details on IS6110 profiles, drug resistance
      status, clinicopathological observations, and host status integrated into the
      analysis process. The strains were found to cluster with possible geographic
      affinities, including the parameters of host species type, IS6110 profile, and
      drug susceptibility status. Of the five most commonly amplified fragment sets (or
      amplitypes), type A predominated in strains of mixed origin, deposited in The
      Netherlands; type B was exclusively observed for Indian isolates; type C was
      found mainly in strains from Peru and Australia; and types D and E predominated
      in European strains from France and Italy. The amplitypes were independent of
      certain large sequence polymorphisms representing two important deletions, TbD1
      and Rd9. It appears that M. tuberculosis has a high genomic diversity with a
      possible geographic evolution. This may have occurred due to specific genomic
      deletions and synonymous substitutions selected rigorously against host defenses
      and environmental stresses on an evolutionary timescale. The genotypic data
      reported here are additionally significant for genotype-phenotype correlations
      and for determining whether pathogen diversity is a reflection f the host
      population diversity.

PMID- 15243089
TI  - High genetic diversity revealed by variable-number tandem repeat genotyping and
      analysis of hsp65 gene polymorphism in a large collection of "Mycobacterium
      canettii" strains indicates that the M. tuberculosis complex is a recently
      emerged clone of "M. canettii".
AB  - We have analyzed, using complementary molecular methods, the diversity of 43
      strains of "Mycobacterium canettii" originating from the Republic of Djibouti, on
      the Horn of Africa, from 1998 to 2003. Genotyping by multiple-locus variable
      number tandem repeat analysis shows that all the strains belong to a single but
      very distant group when compared to strains of the Mycobacterium tuberculosis
      complex (MTBC). Thirty-one strains cluster into one large group with little
      variability and five strains form another group, whereas the other seven are more
      diverged. In total, 14 genotypes are observed. The DR locus analysis reveals
      additional variability, some strains being devoid of a direct repeat locus and
      others having unique spacers. The hsp65 gene polymorphism was investigated by
      restriction enzyme analysis and sequencing of PCR amplicons. Four new single
      nucleotide polymorphisms were discovered. One strain was characterized by three
      nucleotide changes in 441 bp, creating new restriction enzyme polymorphisms. As
      no sequence variability was found for hsp65 in the whole MTBC, and as a single
      point mutation separates M. tuberculosis from the closest "M. canettii" strains,
      this diversity within "M. canettii" subspecies strongly suggests that it is the
      most probable source species of the MTBC rather than just another branch of the
      MTBC.

PMID- 15243090
TI  - Purification of Enterocytozoon bieneusi spores from stool specimens by gradient
      and cell sorting techniques.
AB  - A three-step method for the purification of Enterocytozoon bieneusi spores from
      stool specimens was developed. The primary process of purification of the spores
      from bacterial contaminants involved Percoll gradient centrifugation followed by
      additional separation using cesium chloride density gradient centrifugation. The
      cesium chloride-isolated spores were further purified using a flow cytometer with
      cell sorting capabilities. Sorting was performed without the use of antibodies,
      fluorochromes, or dyes, leaving the sorted spores in their native state, which
      appears to be less destructive for spores. When quantified by flow cytometry
      using tubes with known numbers of highly fluorescent polystyrene beads, the
      sorted material showed a slight decrease in light scatter characteristics
      compared with the slightly larger Encephalitozoon species spores. Although the
      overall recovery of the E. bieneusi spores was low, calcofluor and Gram
      chromotrope staining, indirect immunofluorescence assay, and transmission
      electron microscopy revealed that the sorted material was highly purified and
      contained large numbers of E. bieneusi spores and relatively few bacteria and
      other debris. The sorted material appeared to be sufficiently pure and could be
      used for in vitro culture and for the development of a variety of diagnostic
      reagents as well as in studying the genome of E. bieneusi and host-parasite
      interactions.

PMID- 15243091
TI  - Detection and genotyping of Entamoeba histolytica, Entamoeba dispar, Giardia
      lamblia, and Cryptosporidium parvum by oligonucleotide microarray.
AB  - Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum are the most
      frequently identified protozoan parasites causing waterborne disease outbreaks.
      The morbidity and mortality associated with these intestinal parasitic infections
      warrant the development of rapid and accurate detection and genotyping methods to
      aid public health efforts aimed at preventing and controlling outbreaks. In this
      study, we describe the development of an oligonucleotide microarray capable of
      detecting and discriminating between E. histolytica, Entamoeba dispar, G. lamblia
      assemblages A and B, and C. parvum types 1 and 2 in a single assay. Unique
      hybridization patterns for each selected protozoan were generated by amplifying
      six to eight diagnostic sequences/organism by multiplex PCR; fluorescent labeling
      of the amplicons via primer extension; and subsequent hybridization to a set of
      genus-, species-, and subtype-specific covalently immobilized oligonucleotide
      probes. The profile-based specificity of this methodology not only permitted for
      the unequivocal identification of the six targeted species and subtypes, but also
      demonstrated its potential in identifying related species such as Cryptosporidium
      meleagridis and Cryptosporidium muris. In addition, sensitivity assays
      demonstrated lower detection limits of five trophozoites of G. lamblia. Taken
      together, the specificity and sensitivity of the microarray-based approach
      suggest that this methodology may provide a promising tool to detect and genotype
      protozoa from clinical and environmental samples.

PMID- 15243092
TI  - Development and clinical evaluation of a highly sensitive DNA microarray for
      detection and genotyping of human papillomaviruses.
AB  - Human papillomavirus (HPV) has been found in cervical cancer, tonsillar cancer,
      and certain types of head and neck cancers. We report on a DNA microarray-based
      method for the simultaneous detection and typing of HPVs. The genotype spectrum
      discriminated by this HPV DNA microarray includes 15 high-risk HPV genotypes and
      12 low-risk HPV genotypes. The HPV DNA microarray showed high degrees of
      specificity and reproducibility. We evaluated the performance of the HPV DNA
      microarray by application to three HPV-positive cell lines (HeLa, Caski, and SiHa
      cells) and two HPV-negative cell lines (C33A and A549 cells). The HPV DNA
      microarray successfully identified the known types of HPV present in the cell
      lines. The detection limit of the HPV DNA microarray was at least 100-fold higher
      than that of PCR. To assess the clinical applicability of the HPV DNA microarray,
      we performed the HPV genotyping assay with 73 nonmalignant and malignant samples
      from 39 tonsillar cancer patients. Twenty-five of the 39 (64.1%) malignant
      samples were positive for HPV, whereas 3 of 34 (8.8%) nonmalignant samples were
      positive for HPV. This result shows a preferential association of HPV with
      tonsillar carcinomas. The correlations of the presence of HPV with the grade of
      differentiation and risk factors were not significant. Our data show that the HPV
      DNA microarray may be useful for the diagnosis and typing of HPV in large-scale
      epidemiological studies.

PMID- 15243093
TI  - Use of applied biosystems 7900HT sequence detection system and Taqman assay for
      detection of quinolone-resistant Neisseria gonorrhoeae.
AB  - Mutations in quinolone resistance-determining regions (QRDRs) have been
      associated with quinolone-resistant Neisseria gonorrhoeae (QRNG). Since
      diagnostic nucleic acid amplification tests for gonococci are now in frequent
      use, molecular detection of QRNG could facilitate surveillance in the absence of
      culture. Here we describe a real-time molecular assay for detecting QRDR
      mutations in gonococci.

PMID- 15243094
TI  - LightCycler-based differentiation of Mycobacterium abscessus and Mycobacterium
      chelonae.
AB  - In this study we introduce a rapid procedure to identify Mycobacterium abscessus
      (types I and II) and M. chelonae using LightCycler-based analysis of the hsp65
      gene. Results from 36 clinical strains were compared with hsp65 gene restriction
      analysis and biochemical profiles of bacilli. As all three methods yielded
      identical results for each isolate, this procedure offers an excellent
      alternative to previously established nucleic acid amplification-based techniques
      for the diagnosis of mycobacterial diseases.

PMID- 15243095
TI  - Detailed protocol for purification of Chlamydia pneumoniae elementary bodies.
AB  - A detailed protocol for the growth and harvest of purified elementary bodies of
      Chlamydia pneumoniae is presented. This procedure utilizes a flask-to-flask
      passage scheme designed to achieve high bacterial titers in a short period of
      time.

PMID- 15243096
TI  - Identification of the severe acute respiratory syndrome coronavirus by
      simultaneous multigene DNA sequencing.
AB  - The recent severe acute respiratory syndrome (SARS) outbreak resulted in calls
      for an accurate diagnostic test that can be used not only for routine testing but
      also for generating nucleotide sequences to monitor the epidemic. Although the
      identity of the SARS coronavirus (SARS-CoV) genome was confirmed by DNA
      sequencing, it is impractical to sequence the entire 29-kb SARS-CoV genome on a
      routine basis. Therefore, alternative assay methods such as the enzyme-linked
      immunosorbent assay and PCR have been pursued for routine testing, primarily to
      resolve probable cases. We report here a modification of standard DNA sequencing
      technology for accurate identification of SARS-CoV in routine testing. Instead of
      requiring the sequencing of the whole SARS-CoV genome, our modification enables
      the simultaneous sequencing of three regions of the SARS-CoV genome, the spike
      protein-encoding gene (35 nucleotides), gene M (43 nucleotides), and gene N (45
      nucleotides), in a single electropherogram. Comparing these nucleotide sequences
      to DNA databank entries (National Institutes of Health) conclusively identified
      them as SARS-CoV sequences.

PMID- 15243097
TI  - Influenza B virus victoria group with a new glycosylation site was epidemic in
      Japan in the 2002-2003 season.
AB  - In the 2002-2003 season, influenza B virus Victoria strains were epidemic after a
      6-year absence in Kobe City, Japan. They reacted poorly to the immune ferret sera
      prepared for use against the previous strain. An amino acid substitution in the
      HA1 region caused them to acquire an N-linked glycosylation site.

PMID- 15243098
TI  - Cloning and characterization of Trichophyton rubrum genes encoding actin, Tri r2,
      and Tri r4.
AB  - The three structural genes of Trichophyton rubrum encoding actin (3,429 bp) and
      two antigens, Tri r2 (2,950 bp) and Tri r4 (3,988 bp), were cloned and
      characterized. They contained six, four, and five exons, respectively. The T.
      rubrum actin protein sequence revealed extremely high homology to other fungal
      actins.

PMID- 15243099
TI  - Performance of the MagNA pure LC robot for extraction of Chlamydia trachomatis
      and Neisseria gonorrhoeae DNA from urine and swab specimens.
AB  - DNA from uncentrifuged urines (n = 195 and n = 202) and cervical swabs (n = 221
      and n = 601) was extracted by the MagNA Pure LC robot and the Amplicor method to
      validate the robot's extraction for Chlamydia trachomatis and Neisseria
      gonorrhoeae testing by Roche PCR. The robot provided a highly sensitive and
      specific method of DNA extraction.

PMID- 15243100
TI  - Phenotypic and molecular characterization of erythromycin resistance in four
      isolates of Streptococcus-like gram-positive cocci causing bacteremia.
AB  - Among nine patients with bacteremia caused by Granulicatella or Gemella in a 6
      year period (July 1995 to June 2001), three had bacteremia caused by erythromycin
      resistant Granulicatella adiacens and one had bacteremia caused by erythromycin
      resistant Gemella haemolysans. All four isolates possessed mef genes, whereas
      none possessed ermT, ermTR, or ermB genes.

PMID- 15243101
TI  - Serotypes and genotypes of erythromycin-resistant group B streptococci in Korea.
AB  - Among 78 erythromycin-resistant group B streptococcus (GBS) isolates from Korea,
      ermB was detected in 58 (74.4%), mefA was detected in 14 (17.9%), and ermTR was
      detected in 6 (7.7%). The most prevalent serotypes of erythromycin-resistant GBS
      were V (detected in 34 isolates [43.6%]) and III (detected in 33 isolates
      [42.3%]). All serotype V erythromycin-resistant GBS harbored the ermB gene.

PMID- 15243102
TI  - A novel multiplex real-time PCR assay for rapid typing of major staphylococcal
      cassette chromosome mec elements.
AB  - We describe a novel procedure for rapid typing of the staphylococcal cassette
      chromosome mec element, a molecular marker allowing discrimination between
      community- and hospital-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) strains. Oligonucleotides targeting the recombinase genes were type
      specific and used to type a collection of 399 MRSA isolates recovered during
      patient screening at admission. This novel assay constitutes a valuable tool for
      evaluating the molecular epidemiology of MRSA and adjusting infection control
      strategies against MRSA.

PMID- 15243103
TI  - Genotypic profile of human herpesvirus 8 (Kaposi's sarcoma-associated
      herpesvirus) in urine.
AB  - Human herpesvirus 8 (HHV-8) open reading frame K1 sequences amplified from the
      urine of 5 of 78 (6.4%) infected people in Malawi were monotypic. In two people,
      urinary and oral sequences were genotypically different. Comprehensive evaluation
      of HHV-8 transmission may require characterization of HHV-8 shed both in urine
      and orally.

PMID- 15243104
TI  - Real-time PCR assay for detection and genotype differentiation of Giardia lamblia
      in stool specimens.
AB  - Real-time PCR, using dual-labeled fluorescent probes targeting the beta-giardin
      gene, was used to detect Giardia lamblia in human stool specimens and to
      discriminate between isolates from the two major genetic assemblages of G.
      lamblia infective to humans, assemblages A and B.

PMID- 15243105
TI  - Genetic relatedness and quinolone resistance of Campylobacter jejuni strains
      isolated in 2002 in Hong Kong.
AB  - Pulsed-field gel electrophoresis fingerprints of 98 Campylobacter jejuni isolates
      from patients (85) and chicken carcasses (13) in Hong Kong in 2002 demonstrated
      high genetic diversity. The prevalence of quinolone resistance among the isolates
      was 85.9%, and replacement of the threonine-86 residue in the gyrase subunit A
      was the major resistance mechanism.

PMID- 15243106
TI  - Application of oxidation-reduction assay for monitoring treatment of patients
      with pulmonary tuberculosis.
AB  - By oxidation-reduction assay, the viability of Mycobacterium tuberculosis in
      sputum specimens was evaluated. The technique is based on the Alamar Blue and
      Malachite Green dyes, which change their color in response to M. tuberculosis
      growth. The method is simple, permits visual reading of results, and is
      applicable for laboratories with limited resources.

PMID- 15243107
TI  - Evaluation of a real-time PCR assay using the LightCycler system for detection of
      parvovirus B19 DNA.
AB  - We evaluated the artus RealArt Parvovirus B19 LC PCR reagent (artus biotech USA,
      San Francisco, Calif.) for real-time PCR detection of parvovirus B19 DNA by
      retesting 71 specimens previously submitted to our laboratory. The artus assay,
      which produces a quantitative result and provides an internal PCR control,
      appeared to be slightly more sensitive than our conventional qualitative PCR
      assay.

PMID- 15243108
TI  - Epidemiological investigation of bloodstream infections by extended spectrum
      cephalosporin-resistant Escherichia coli in a Taiwanese teaching hospital.
AB  - In an epidemiologic and case-control study including 30 case patients over a 3.5
      year period in a Taiwanese university hospital, only beta-lactamase inhibitor use
      and extended-spectrum cephalosporin use were identified as independent risk
      factors for nosocomial CMY-2-producing Escherichia coli bloodstream infection,
      and CMY-2 producers were found more prevalent than extended-spectrum beta
      lactamase-producing isolates.

PMID- 15243109
TI  - Detection of Pneumocystis jiroveci in respiratory specimens by four staining
      methods.
AB  - We examined four staining methods on replicate smears of 313 respiratory
      specimens submitted for Pneumocystis jiroveci examination. The sensitivity and
      specificity of Calcofluor white stain (CW) were 73.8 and 99.6%, respectively. The
      sensitivity and specificity of Grocott-Gomori methenamine silver stain (GMS) were
      79.4 and 99.2%, respectively. The sensitivity and specificity of Diff-Quik stain
      were 49.2 and 99.6%, respectively. The sensitivity and specificity of Merifluor
      Pneumocystis stain were 90.8 and 81.9%, respectively. Only CW and GMS had
      positive and negative predictive values of >90%.

PMID- 15243110
TI  - Direct identification of Mycobacterium haemophilum in skin lesions of
      immunocompromised patients by PCR-restriction endonuclease analysis.
AB  - PCR-restriction endonuclease analysis (PRA) was used for direct identification of
      Mycobacterium haemophilum in clinical specimens from immunocompromised patients.
      PRA correctly identified M. haemophilum in four smear-positive specimens. Direct
      identification by PRA takes 2 to 3 working days compared to the 3 to 5 weeks
      required for culture isolation and identification by conventional methods.

PMID- 15243111
TI  - Diagnostic utility and clinical significance of naso- and oropharyngeal samples
      used in a PCR assay to diagnose Mycoplasma pneumoniae infection in children with
      community-acquired pneumonia.
AB  - PCR assays of naso- and oropharyngeal samples among hospitalized children appear
      equally effective for the diagnosis of serologically confirmed community-acquired
      mycoplasmal pneumonia. However, the combination of results from both sites yields
      optimal sensitivity (57%), specificity (98%), and positive (92%) and negative
      (82%) predictive values when compared with Mycoplasma pneumoniae enzyme-linked
      immunosorbent assay.

PMID- 15243112
TI  - Differences in clinical manifestation of Streptococcus pneumoniae infection are
      not correlated with in vitro production and release of the virulence factors
      pneumolysin and lipoteichoic and teichoic acids.
AB  - Production and release of the pneumococcal virulence factors pneumolysin and
      lipoteichoic and teichoic acid in 75 clinical isolates were investigated. No
      difference was found between strains causing systemic infection or localized
      respiratory infection and isolates from asymptomatic carriers. This suggests that
      the presence of pneumolysin and lipoteichoic and teichoic acid is a necessary but
      not a sufficient condition for pneumococcal infection and development of invasive
      disease.

PMID- 15243113
TI  - Evaluation of indirect fluorescence antibody assay for detection of Bartonella
      clarridgeiae and Seroprevalence of B. clarridgeiae among patients with suspected
      cat scratch disease.
AB  - The possibility of Bartonella clarridgeiae being a causative agent of cat scratch
      disease (CSD) was investigated by using indirect fluorescence antibody assays
      with 288 suspected CSD patients. Immunoglobulin G antibody to noncocultivated B.
      clarridgeiae was suitable only for detection of B. clarridgeiae antibody.
      Significant cross-reactivity between Bartonella henselae and B. clarridgeiae was
      noted, and no CSD case caused by B. clarridgeiae was detected.

PMID- 15243114
TI  - Use of two sensitive and specific immunoblot markers, em70 and em90, for
      diagnosis of alveolar echinococcosis.
AB  - Antibodies against Echinococcus multilocularis metacestodes were screened by
      immunoblotting sera from patients with alveolar echinococcosis (n = 39), cystic
      echinococcosis (n = 109), or other parasitic infections (n = 66) and healthy
      individuals (n = 32). Two antigens, approximately 70 and 90 kDa, are found to be
      valuable for confirmatory diagnosis, with a sensitivity and specificity of 100
      and 99.51%, respectively.

PMID- 15243116
TI  - Quality control guidelines for BAL9141 (Ro 63-9141), an investigational
      cephalosporin, when reference MIC and standardized disk diffusion susceptibility
      test methods are used.
AB  - BAL9141 is a novel cephalosporin with a broad spectrum of activity, including
      activity against methicillin-resistant staphylococci. This multicenter study was
      performed to establish quality control (QC) guidelines for susceptibility testing
      of BAL9141 in phase 3 clinical trials and after U.S. Food and Drug Administration
      approval. The proposed 3 or 4 log(2) dilution MIC ranges encompass 97.8 to 100.0%
      of reported results, while the proposed 7- to 9-mm-zone-diameter QC ranges
      included 95.2 to 99.4% of the participant-reported disk diffusion results.

PMID- 15243115
TI  - Clinical and microbiological analysis of bloodstream infections caused by
      Chryseobacterium meningosepticum in nonneonatal patients.
AB  - Chryseobacterium meningosepticum bloodstream infections in 11 nonneonatal
      patients were reported. More than half of the infections were community acquired.
      PCR assays indicated that the organisms produced extended-spectrum beta
      lactamases as well as metallo-beta-lactamases. Genotyping showed diverse
      fingerprints among the isolates. Six patients survived without appropriate
      antibiotic treatment. Host factors are the major determinant of the outcomes of
      C. meningosepticum infections.

PMID- 15243117
TI  - Extended-spectrum-beta-lactamase (TEM-52)-producing strains of Salmonella
      enterica of various serotypes isolated in France.
AB  - From 2002 to 2003, four isolates of Salmonella enterica serotypes Typhimurium,
      Enteritidis, Blockley, and Panama, isolated in France from patients with
      gastroenteritis, were found to produce extended-spectrum beta-lactamase TEM-52.
      The study showed the bla(TEM-52) gene to be located in a Tn3-like structure and
      carried by 100- or 32-kb conjugative plasmids.

PMID- 15243118
TI  - Fungemia caused by Zygoascus hellenicus in an allogeneic stem cell transplant
      recipient.
AB  - Zygoascus hellenicus (Candida hellenica) was isolated from a blood culture from a
      patient who had received an allogeneic stem cell transplant. The isolate
      displayed an antifungal susceptibility pattern of decreased susceptibility to
      fluconazole and itraconazole, high susceptibility to voriconazole, and low
      susceptibility to caspofungin. The organism was misidentified by a commercial
      yeast identification system. This is the first reported case of human infection
      with this rare ascomycetous yeast.

PMID- 15243119
TI  - First comprehensively documented case of Paracoccus yeei infection in a human.
AB  - Paracoccus yeei was isolated in pure culture from an aerobic blood culture and
      bulla fluid from a 67-year-old male. The biochemical identification scheme for
      this recently described species is outlined. Because of its reaction pattern it
      is not unlikely that P. yeei is underdiagnosed.

PMID- 15243120
TI  - Septic arthritis of the knee due to Fusobacterium necrophorum.
AB  - Gram-negative, anaerobic bacilli are unusual organisms to be isolated in cases of
      acute septic arthritis. We report the isolation of Fusobacterium necrophorum from
      joint aspirate in a case of acute septic arthritis, which presented 3 weeks after
      the drainage of a dental abscess.

PMID- 15243121
TI  - Prosthetic mitral valve endocarditis due to Ochrobactrum anthropi: case report.
AB  - We describe a case of infective endocarditis in a prosthetic mitral valve due to
      Ochrobactrum anthropi. Although O. anthropi is an emerging pathogen in
      immunocompromised patients, infections with the bacterium have very rarely been
      documented in healthy hosts, and endocarditis is rare. To our knowledge, only two
      cases of O. anthropi endocarditis have been reported in the medical literature.

PMID- 15243122
TI  - Bacteriology of a bear bite wound to a human: case report.
AB  - Human contact with bears has become more frequent, as has the resultant bear
      maulings and bite injuries. We report the bacteriology of a patient bitten by a
      grizzly bear (Ursus arctos) from the Rocky Mountains foothills area east of Banff
      National Park, Alberta, Canada. The patient received field care, including
      metronidazole and cefazolin. Subsequent deep-wound cultures grew Serratia
      fonticola, Serratia marcescens, Aeromonas hydrophila, Bacillus cereus, and
      Enterococcus durans but no anaerobes.

PMID- 15243123
TI  - Legionella pneumophila serogroup 1 antigen can be detected in sputum samples by
      an immunochromatographic assay.

PMID- 15243124
TI  - Human tracheopulmonary myiasis.

PMID- 15243125
TI  - Internal amplification control for PCR should not be mandatory in the clinical
      medical environment.

PMID- 15243126
TI  - Differential localization and expression of urokinase plasminogen activator
      (uPA), its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in
      endometrial tissue during the menstrual cycle.
AB  - Normal endometrium is a highly dynamic tissue, which responds to ovarian steroids
      with cyclic proliferation, differentiation (secretion), and degradation
      (menstruation). The urokinase plasminogen activator (uPA)-dependent proteolytic
      cascade as well as ligand activation of the uPA receptor (uPAR) is critically
      involved in physiological as well as pathophysiological aspects of tissue
      expansion and remodelling. Cyclic variation and distribution of uPA, uPAR and
      plasminogen activator inhibitor 1 (PAI-1) mRNA were examined by in situ
      hybridization, real-time PCR and northern blot in normal endometrium. Their
      corresponding proteins were localized with immunohistochemistry. uPA mRNA is
      exclusively expressed by stromal cells, whereas uPA protein is present in both
      epithelial and stromal cells. Immunostaining for uPA protein is reduced or
      undetectable at midcycle, thus coinciding with peak concentration of uPA in the
      uterine fluid. uPAR mRNA is expressed by epithelial cells in the proliferative
      phase and by stromal cells in the secretory phase. However, epithelial cells
      stain for uPAR protein throughout the cycle, suggesting that uPAR may detach from
      stromal cells and then bind to epithelial cells in the secretory phase. PAI-1
      mRNA is located in vessel walls. The late secretory phase has greatly increased
      expression of all three mRNA and their proteins, mainly in pre-decidual cells in
      the superficial stroma. Discordant localization of the mRNA and proteins suggest
      that uPA is produced by stromal cells, released and bound to epithelial cells in
      both the proliferative and secretory phases, whereas uPAR is released from the
      stroma and bound to epithelial cells in the secretory phase. Also, the present
      data together with earlier reports suggest that uPA is released from the
      epithelial cells to the uterine fluid.

PMID- 15243127
TI  - Basic fibroblast growth factor expression in isolated small human ovarian
      follicles.
AB  - Basic fibroblast growth factor (bFGF) is involved in cell proliferation,
      differentiation, and angiogenesis. It has long been known that bFGF acts as a
      powerful mitogen for various mammalian granulosa cells in culture. To investigate
      the possible involvement of bFGF expression in follicle initiation and growth in
      vivo, we performed nested RT-PCR on ovarian cortical biopsies and quantitative
      PCR on human follicle populations isolated by laser capture microdissection.
      Using morphological criteria, follicles were characterized as putative non
      growing, primary, or small secondary. RNA was extracted from samples, reverse
      transcribed, and relative gene expression levels determined with TaqMan real-time
      PCR, using 18S rRNA as the endogenous control. Results confirmed bFGF expression
      in human adult ovarian cortex, and in the isolated follicles a down-regulation of
      bFGF mRNA was evident as small follicles develop. This study demonstrates a
      possible relationship between bFGF mRNA expression and follicle development.

PMID- 15243128
TI  - Immortalization and characterization of human myometrial cells from term-pregnant
      patients using a telomerase expression vector.
AB  - An examination of cellular processes involved in myometrial function has been
      greatly assisted by the use of human myometrial cells in primary culture.
      However, these cells can be used only for several passages before they senesce,
      and responses to various agents change with time in culture. The use of
      transformed cells is limited, as they can be polynucleated and can lose or gain
      chromosomes. We have developed three telomerase-immortalized cell lines from term
      pregnant human myometrium to eliminate variability between passage numbers and
      allow genetic manipulations of myometrial cells to fully characterize signal
      pathways. These cells have a normal karyotype and were verified to be uterine
      smooth muscle by immunocytochemical staining for smooth muscle cell-specific
      alpha-actin and high affinity oxytocin antagonist binding sites. The three cell
      lines and the cells in primary culture from which they were derived were examined
      by cDNA microarray analysis. Of >10 000 expressed genes, there were consistent
      changes in the expression of approximately 1% in the three immortalized cell
      lines. We were unable to detect any significant differences between primary and
      immortalized cells in signal pathways such as epidermal growth factor-stimulated
      epidermal growth factor receptor phosphorylation, insulin-stimulated Akt
      phosphorylation, oxytocin and lysophosphatidic acid-stimulated extracellular
      signal-regulated kinase 1 and 2 phosphorylation, myosin light chain
      phosphorylation, and interleukin-1 induction of IkappaBalpha degradation. The
      immortalized cells should be useful for a range of studies, including high
      throughput analyses of the effects of environmental agents on the human
      myometrium.

PMID- 15243129
TI  - Reexpression of p8 contributes to tumorigenic properties of pituitary cells and
      appears in a subset of prolactinomas in transgenic mice that hypersecrete
      luteinizing hormone.
AB  - Targeted overexpression of LH in transgenic mice causes hyperproliferation of Pit
      1-positive pituitary cells and development of functional adenomas. To
      characterize gene expression changes associated with pituitary tumorigenesis, we
      performed microarray studies using Affymetrix GeneChips comparing expression
      profiles from pituitary tumors in LH-overexpressing mice to wild-type control
      pituitaries. We identified a number of candidate genes with altered expression in
      pituitary tumors. One of these, p8 (candidate of metastasis-1), encodes a native
      high-mobility group-like transcription factor previously shown to be necessary
      for ras-mediated transformation of mouse embryonic fibroblasts and also
      implicated in breast cancer progression. Herein, we show that expression of p8,
      normally quiescent in adult pituitary, localizes to tumor foci containing
      lactotropes, suggesting a linkage with their transformation. To further establish
      the functional significance of p8 in pituitary tumorigenesis, we constructed
      several clonal cell lines with reduced expression of p8 from a parent GH3
      somatolactotrope cell line. These clonal derivates, along with the parent cell
      line, were tested for tumorigenicity by injection into athymic mice. When
      compared with wild-type GH3 with higher levels of p8, GH3 cells with reduced
      expression of p8 displayed attenuated tumor development or failed to develop
      tumors at all. Similar results were obtained with gonadotrope-derived cell lines
      that displayed reduced expression of p8. Together, these data suggest that
      maintenance of the transformed phenotype of pituitary GH3 cells requires
      expression of p8 and that it may play a similar role when reexpressed in a subset
      of lactotropes that form prolactinomas in vivo.

PMID- 15243130
TI  - Down-regulation by nuclear factor kappaB of human 25-hydroxyvitamin D3 1alpha
      hydroxylase promoter.
AB  - 1,25-(OH)(2) vitamin D(3) is important for calcium homeostasis and cell
      differentiation. The key enzyme for the activation of liver-derived 25(OH)
      vitamin D(3) is 25-hydroxyvitamin D(3) 1alpha-hydroxylase. It is expressed mainly
      in the kidney but also in peripheral tissues. A 1413-bp fragment of the 1alpha
      hydroxylase promoter was cloned into luciferase vectors pGL2basic and pGL3basic.
      Sequence analyses revealed four base exchanges and three base deletions compared
      with the published sequence which were identically found in five control persons.
      In silico promoter analyses revealed 17 putative nuclear factor (NF)kappaB sites,
      10 of which were found to bind NFkappaB in EMSA experiments. Cotransfection of
      NFkappaB p50 and p65 subunits resulted in dramatic reduction of the promoter
      activity of the full-length construct as well as a series of 5'-deletion
      constructs. Deletion of the farmost 3'-situated NFkappaB-responsive element
      almost abolished NFkappaB responsiveness. Treatment of human embryonic kidney 293
      cells with sulfasalazine, a NFkappaB inhibitor, resulted in enhanced 1alpha
      hydroxylase mRNA production. Down-regulation of 1alpha-hydroxylase promoter
      through NFkappaB signaling may contribute to the pathogenesis of inflammation
      associated osteopenia/osteoporosis.

PMID- 15243131
TI  - Mechanisms regulating the constitutive activation of the extracellular signal
      regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of
      ribonucleic acid interference for ERK1/2 on cancer cell proliferation.
AB  - The ERK1/2 MAPK pathway is a critical signaling system that mediates ligand
      stimulated signals for the induction of cell proliferation, differentiation, and
      cell survival. Studies have shown that this pathway is constitutively active in
      several human malignancies and may be involved in the pathogenesis of these
      tumors. In the present study we examined the ERK1/2 pathway in cell lines derived
      from epithelial and granulosa cell tumors, two distinct forms of ovarian cancer.
      We show that ERK1 and ERK2 are constitutively active and that this activation
      results from both MAPK kinase-dependent and independent mechanisms and is
      correlated with elevated BRAF expression. MAPK phosphatase 1 (MKP-1) expression,
      which is involved in ERK1/2 deactivation, is down-regulated in the cancer cells,
      thus further contributing to ERK hyperactivity in these cells. Treatment of these
      cancer cell lines with the proteasome inhibitor ZLLF-CHO increased MKP-1 but not
      MKP-2 expression and decreased ERK1/2 phosphorylation. More importantly,
      silencing of ERK1/2 protein expression using RNA interference led to the complete
      suppression of tumor cell proliferation. These results provide evidence that the
      ERK pathway plays a major role in ovarian cancer pathogenesis and that down
      regulation of this master signaling pathway is highly effective for the
      inhibition of ovarian tumor growth.

PMID- 15243132
TI  - Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on
      firing up adipose tissue metabolism.
AB  - The three beta AR (beta-adrenergic receptor) subtypes (beta(1)AR, beta(2)AR, and
      beta(3)AR) are members of the large family of G protein-coupled receptors, each
      of which is coupled to G alpha s and increases in intracellular cAMP levels. In
      white adipose tissues, catecholamine activation of the beta ARs leads to the
      mobilization of stored fatty acids and regulates release of several adipokines,
      whereas in brown adipose tissue they stimulate the specialized process of
      adaptive nonshivering thermogenesis. Noteworthy, in most models of obesity the
      beta AR system is dysfunctional, and its ability to stimulate lipolysis and
      thermogenesis are both impaired. Nevertheless, selective agonists for the
      beta(3)AR, a subtype that is found predominantly in adipocytes, have been able to
      prevent or reverse obesity and accompanying insulin resistance in animal models.
      Whether this is a viable therapeutic option for human obesity is much debated
      with regard to the existence of brown adipocytes in humans or their ability to be
      recruited. Nevertheless, probing the physiological changes in adrenoceptor
      function in rodent obesity, as well as the process by which beta(3)AR agonists
      promote a thermogenic shift in fuel use, have yielded unexpected new insights
      into beta AR signaling and adipocyte physiology. These include the recent
      discovery of an essential role of p38 MAPK in mediating adaptive thermogenesis,
      as well as the accessory role of the ERK MAPK pathway for the control of
      lipolysis. Because these metabolic events were traditionally ascribed solely to
      the cAMP/protein kinase A system, the integration of these signaling mechanisms
      may pose new therapeutic directions in the quest to counter the obesity epidemic
      in our midst.

PMID- 15243133
TI  - Postural and locomotor control in normal and vestibularly deficient mice.
AB  - We investigated how vestibular information is used to maintain posture and
      control movement by studying vestibularly deficient mice (IsK-/- mutant). In
      these mutants, microscopy showed degeneration of the cristae of the semicircular
      canals and of the maculae of the utriculi and sacculi, while behavioural and
      vestibulo-ocular reflex testing showed that vestibular function was completely
      absent. However, the histology of Scarpa's ganglia and the vestibular nerves was
      normal in mutant mice, indicating the presence of intact central pathways. Using
      X-ray and high-speed cineradiography, we compared resting postures and locomotion
      patterns between these vestibularly deficient mice and vestibularly normal mice
      (wild-type and IsK+/-). The absence of vestibular function did not affect resting
      posture but had profound effects on locomotion. At rest, the S-shaped, sagittal
      posture of the vertebral column was the same for wild-type and mutant mice. Both
      held the head with the atlanto-occipital joint fully flexed, the cervico-thoracic
      junction fully flexed, and the cervical column upright. Wild-type mice extended
      the head and vertebral column and could walk in a straight line. In marked
      contrast, locomotion in vestibularly deficient mice was characterized by circling
      episodes, during which the vertebral column maintained an S-shaped posture. Thus,
      vestibular information is not required to control resting posture but is
      mandatory for normal locomotion. We propose that vestibular inputs are required
      to signal the completion of a planned trajectory because mutant mice continued
      rotating after changing heading direction. Our findings support the hypothesis
      that vertebrates limit the number of degrees of freedom to be controlled by
      adopting just a few of the possible skeletal configurations.

PMID- 15243134
TI  - A quantitative analysis of cell volume and resting potential determination and
      regulation in excitable cells.
AB  - This paper quantifies recent experimental results through a general physical
      description of the mechanisms that might control two fundamental cellular
      parameters, resting potential (Em) and cell volume (Vc), thereby clarifying the
      complex relationships between them. Em was determined directly from a charge
      difference (CD) equation involving total intracellular ionic charge and membrane
      capacitance (Cm). This avoided the equilibrium condition dEm/dt = 0 required in
      determinations of Em by previous work based on the Goldman-Hodgkin-Katz equation
      and its derivatives and thus permitted precise calculation of Em even under non
      equilibrium conditions. It could accurately model the influence upon Em of
      changes in Cm or Vc and of membrane transport processes such as the Na+-K+-ATPase
      and ion cotransport. Given a stable and adequate membrane Na+-K+-ATPase density
      (N), Vc and Em both converged to unique steady-state values even from sharply
      divergent initial intracellular ionic concentrations. For any constant set of
      transmembrane ion permeabilities, this set point of Vc was then determined by the
      intracellular membrane-impermeant solute content (X-i) and its mean charge
      valency (zX), while in contrast, the set point of Em was determined solely by zX.
      Independent changes in membrane Na+ (PNa) or K+ permeabilities (PK) or activation
      of cation-chloride cotransporters could perturb Vc and Em but subsequent reversal
      of such changes permitted full recovery of both Vc and Em to the original set
      points. Proportionate changes in PNa, PK and N, or changes in Cl- permeability
      (PCl) instead conserved steady-state Vc and Em but altered their rates of
      relaxation following any discrete perturbation. PCl additionally determined the
      relative effect of cotransporter activity on Vc and Em, in agreement with recent
      experimental results. In contrast, changes in Xi- produced by introduction of a
      finite permeability term to X- (PX) that did not alter zX caused sustained
      changes in Vc that were independent of Em and that persisted when PX returned to
      zero. Where such fluxes also altered the effective zX they additionally altered
      the steady state Em. This offers a basis for the suggested roles of amino acid
      fluxes in long-term volume regulatory processes in a variety of excitable
      tissues.

PMID- 15243135
TI  - Postsynaptic production of nitric oxide implicated in long-term depression at the
      mature amphibian (Bufo marinus) neuromuscular junction.
AB  - We report here evidence for endogenous NO signalling in long-term (>1 h) synaptic
      depression at the neuromuscular junction induced by 20 min of 1 Hz nerve
      stimulation. Synaptic depression was characterized by a 46% reduction in the end
      plate potential (EPP) amplitude and a 21% decrease in miniature EPP (MEPP)
      frequency, but no change to MEPP amplitude, indicating a reduction in evoked
      quantal release. Both the membrane-impermeant NO scavenger cPTIO and the NOS
      inhibitor L-NAME blocked depression, suggesting that it is induced by NO
      originating from a source outside the terminal. The depression was dependent on
      activation of muscle-type, but not neuronal-type, nAChRs and was still observed
      when Ca2+ release from the sarcoplasmic reticulum and muscle contraction were
      blocked with dantrolene. These data suggest that the depression depends on
      transmission, but not muscle contraction. The calcineurin inhibitors cyclosporin
      A and FK506, as well as ODQ, an inhibitor of NO-sensitive soluble guanylyl
      cyclase, Rp-8-pCPT-cGMPS, an inhibitor of cGMP-dependent protein kinase, and the
      calmodulin antagonist phenoxybenzamine also blocked depression. We propose that
      low frequency synaptic transmission leads to production of NO at the synapse and
      depression of transmitter release via a cGMP-dependent mechanism. The NO could be
      generated either directly from the muscle, or possibly from the Schwann cell in
      response to an unidentified muscle-derived messenger. We showed that the long
      lasting depression of transmitter release was due to sustained activity of the NO
      signalling pathway, and suggest dephosphorylation of NOS by calcineurin as the
      basis for continued NO production.

PMID- 15243136
TI  - Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in
      mammalian ventricular myocytes.
AB  - After sarcoplasmic reticulum (SR) Ca2+ depletion in intact ventricular myocytes,
      electrical activity promotes SR Ca2+ reloading and recovery of twitch amplitude.
      In ferret, recovery of twitch and caffeine-induced contracture required fewer
      twitches than in rabbit or rat. In rat, there was no difference in action
      potential duration at 90% repolarization (APD90) at steady state (SS) versus at
      the first post-depletion (PD) twitch. The SS APD90 was similar in ferret and
      rabbit (but longer than in rat). However, compared to SS, the PD APD90 was
      lengthened in ferret, but shortened in rabbit. When rabbit myocytes were
      subjected to AP-clamp patterns during SR Ca2+ reloading (ferret- or rabbit-type
      APs), reloading was much faster using the ferret AP templates. We conclude that
      the faster SR Ca2+ refilling in ferret is due to the increased Ca2+ influx during
      the longer PD AP. The PD versus SS APD90 difference was suppressed by
      thapsigargin in ferret (indicating Ca2+ dependence). In rabbit, the PD AP
      shortening depended on the preceding diastolic interval (rather than Ca2+),
      because rest produced the same AP shortening, and SS APD90 increased as a
      function of frequency (in contrast to ferret). Transient outward current (Ito)
      was larger and recovered from inactivation much faster in ferret than in rabbit.
      Moreover, slow Ito recovery (tau approximately 3 s) in rabbit was a much larger
      fraction of Ito. Our data and a computational model (including two Ito
      components) suggest that in rabbit the slowly recovering Ito is responsible for
      short post-rest and PD APs, for the unusual frequency dependence of APD90, and
      ultimately for the slower post-depletion SR Ca2+ reloading.

PMID- 15243137
TI  - Nerve growth factor favours long-term depression over long-term potentiation in
      layer II-III neurones of rat visual cortex.
AB  - Nerve growth factor (NGF) has been shown to regulate plasticity in the visual
      cortex of monocularly deprived animals. However, to date, few attempts have been
      made to investigate the role of NGF in synaptic plasticity at the cellular level.
      In the study reported here we looked at the effects of exogenously applied NGF on
      synaptic plasticity of layer II-III regular spiking (RS) neurones in visual
      cortex of 16- to 18-day-old rats. We found that local application of NGF
      converted high frequency stimulation (HFS)-induced long-term potentiation (LTP)
      into long-term depression (LTD). We showed that this shift of synaptic plasticity
      was also obtained with bath application of NGF during HFS. Application of NGF
      subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF
      efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of
      TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low
      frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or
      blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of
      the LTD induced by LFS. Thus, the NGF effect is selective for synaptic
      modifications induced by HFS in RS cells. The present results indicate that NGF
      may modulate the sign of long-term changes of synaptic efficacy in response to
      high frequency inputs.

PMID- 15243138
TI  - Mechanism of spontaneous excitability in human embryonic stem cell derived
      cardiomyocytes.
AB  - Human embryonic stem cell-derived cardiomyocytes (hES-CMs) are thought to
      recapitulate the embryonic development of heart cells. Given the exciting
      potential of hES-CMs as replacement tissue in diseased hearts, we investigated
      the pharmacological sensitivity and ionic current of mid-stage hES-CMs (20-35
      days post plating). A high-resolution microelectrode array was used to assess
      conduction in multicellular preparations of hES-CMs in spontaneously contracting
      embryoid bodies (EBs). TTX (10 microm) dramatically slowed conduction velocity
      from 5.1 to 3.2 cm s(-1) while 100 microm TTX caused complete cessation of
      spontaneous electrical activity in all EBs studied. In contrast, the Ca2+channel
      blockers nifedipine or diltiazem (1 microm) had a negligible effect on
      conduction. These results suggested a prominent Na+ channel current, and
      therefore we patch-clamped isolated cells to record Na+ current and action
      potentials (APs). We found for isolated hES-CMs a prominent Na+ current (244 +/-
      42 pA pF(-1) at 0 mV; n=19), and a hyperpolarization-activated current (HCN), but
      no inward rectifier K+ current. In cell clusters, 3 microm TTX induced longer AP
      interpulse intervals and 10 microm TTX caused cessation of spontaneous APs. In
      contrast nifedipine (Ca2+ channel block) and 2 mm Cs+ (HCN complete block)
      induced shorter AP interpulse intervals. In single cells, APs stimulated by
      current pulses had a maximum upstroke velocity (dV/dtmax) of 118 +/- 14 V s(-1)
      in control conditions; in contrast, partial block of Na+ current significantly
      reduced stimulated dV/dtmax (38 +/- 15 V s(-1)). RT-PCR revealed NaV1.5, CaV1.2,
      and HCN-2 expression but we could not detect Kir2.1. We conclude that hES-CMs at
      mid-range development express prominent Na+ current. The absence of background K+
      current creates conditions for spontaneous activity that is sensitive to TTX in
      the same range of partial block of NaV1.5; thus, the NaV1.5 Na+ channel is
      important for initiating spontaneous excitability in hES-derived heart cells.

PMID- 15243139
TI  - Slow skeletal muscles of the mouse have greater initial efficiency than fast
      muscles but the same net efficiency.
AB  - The aim of this study was to determine whether the net efficiency of mammalian
      muscles depends on muscle fibre type. Experiments were performed in vitro (35
      degrees C) using bundles of muscle fibres from the slow-twitch soleus and fast
      twitch extensor digitorum longus (EDL) muscles of the mouse. The contraction
      protocol consisted of 10 brief contractions, with a cyclic length change in each
      contraction cycle. Work output and heat production were measured and enthalpy
      output (work + heat) was used as the index of energy expenditure. Initial
      efficiency was defined as the ratio of work output to enthalpy output during the
      first 1 s of activity. Net efficiency was defined as the ratio of the total work
      produced in all the contractions to the total, suprabasal enthalpy produced in
      response to the contraction series, i.e. net efficiency incorporates both initial
      and recovery metabolism. Initial efficiency was greater in soleus (30 +/- 1%;
      n=6) than EDL (23 +/- 1%; n=6) but there was no difference in net efficiency
      between the two muscles (12.6 +/- 0.7% for soleus and 11.7 +/- 0.5% for EDL).
      Therefore, more recovery heat was produced per unit of initial energy expenditure
      in soleus than EDL. The calculated efficiency of oxidative phosphorylation was
      lower in soleus than EDL. The difference in recovery metabolism between soleus
      and EDL is unlikely to be due to effects of changes in intracellular pH on the
      enthalpy change associated with PCr hydrolysis. It is suggested that the
      functionally important specialization of slow-twitch muscle is its low rate of
      energy use rather than high efficiency.

PMID- 15243140
TI  - A novel physiological mechanism of glycine-induced immunomodulation: Na+-coupled
      amino acid transporter currents in cultured brain macrophages.
AB  - Glycine is known to modulate immune cell responses. However, the physiological
      mechanisms underlying inhibitory effects of glycine on macrophages are not well
      understood. Here we show that glycine is capable of inducing inward currents in
      brain macrophages (microglia). In contrast to glycine, the glycine receptor
      agonist taurine failed to elicit currents. Glycine-evoked currents of brain
      macrophages were unaffected by strychnine, Cl(-)-free extracellular solution, N
      [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (NFPS) and amoxapine,
      but were abolished upon omission of extracellular Na(+). Furthermore, glycine
      caused increases in the intracellular Na(+) concentration and pronounced membrane
      depolarization. Glycine-evoked depolarization was Na(+) dependent and occurred
      independently of the intracellular Cl(-) concentration. Similarly to glycine,
      glutamine and alpha-(methylamino)isobutyric acid (MeAIB) elicited inward currents
      in brain macrophages. In the presence of either glutamine or MeAIB, glycine
      induced currents were inhibited. It is concluded that neither functional glycine
      receptors nor glycine transporters are expressed in brain macrophages. We suggest
      that glycine mediates its effects by activation of system A Na(+)-coupled neutral
      amino acid transporters.

PMID- 15243141
TI  - Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and
      inhibits CBF-mediated transcription activation in vitro.
AB  - To understand the role of the CCAAT-binding factor, CBF, in transcription, we
      developed a strategy to purify the heterotrimeric CBF complex from HeLa cell
      extracts using two successive immunoaffinity chromatography steps. Here we show
      that the p32 protein, previously identified as the ASF/SF2 splicing factor
      associated protein, copurified with the CBF complex. Studies of protein-protein
      interaction demonstrated that p32 interacts specifically with CBF-B subunit and
      also associates with CBF-DNA complex. Cellular localization by immunofluorescence
      staining revealed that p32 is present in the cell throughout the cytosol and
      nucleus, whereas CBF is present primarily in the nucleus. A portion of the p32
      colocalizes with CBF-B in the nucleus. Interestingly, reconstitution of p32 in an
      in vitro transcription reaction demonstrated that p32 specifically inhibits CBF
      mediated transcription activation. Altogether, our study identified p32 as a
      novel and specific corepressor of CBF-mediated transcription activation in vitro.

PMID- 15243142
TI  - Optimization of probe length and the number of probes per gene for optimal
      microarray analysis of gene expression.
AB  - Gene-specific oligonucleotide probes are currently used in microarrays to avoid
      cross-hybridization of highly similar sequences. We developed an approach to
      determine the optimal number and length of gene-specific probes for accurate
      transcriptional profiling studies. The study surveyed probe lengths from 25 to
      1000 nt. Long probes yield better signal intensity than short probes. The signal
      intensity of short probes can be improved by addition of spacers or using higher
      probe concentration for spotting. We also found that accurate gene expression
      measurement can be achieved with multiple probes per gene and fewer probes are
      needed if longer probes rather than shorter probes are used. Based on theoretical
      considerations that were confirmed experimentally, our results showed that 150mer
      is the optimal probe length for expression measurement. Gene-specific probes can
      be identified using a computational approach for 150mer probes and they can be
      treated like long cDNA probes in terms of the hybridization reaction for high
      sensitivity detection. Our experimental data also show that probes which do not
      generate good signal intensity give erroneous expression ratio measurement
      results. To use microarray probes without experimental validation, gene-specific
      probes approximately 150mer in length are necessary. However, shorter
      oligonucleotide probes also work well in gene expression analysis if the probes
      are validated by experimental selection or if multiple probes per gene are used
      for expression measurement.

PMID- 15243143
TI  - Effects of hsp70.1 gene knockout on the mitochondrial apoptotic pathway after
      focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Murine heat-shock protein 70 (HSP70) protein, which is
      produced from 2 genes, hsp70.1 and hsp70.3, is known to protect the brain against
      ischemic injury. However, little information is available on the antiapoptotic
      mechanism of HSP70.1 protein after cerebral ischemia. To evaluate the role of
      HSP70.1 protein in ischemia, we analyzed the mitochondrial apoptotic pathway
      using hsp70.1 knockout (KO) mice and their wild-type (WT) mice. METHODS: hsp70.1
      KO and WT mice underwent focal ischemia for 120 minutes. DNA fragmentation was
      evaluated by TUNEL staining. Cytochrome c release and the activation of caspase-3
      were analyzed by Western blotting and immunohistochemistry. RESULTS: hsp70.1 mRNA
      was not detected in hsp70.1 KO mice after ischemia, and HSP70 protein expression
      was markedly suppressed versus WT mice. KO mice showed a significantly greater
      infarction volume and DNA fragmentation in the cortex than WT mice at 24 hours
      after ischemia. At 8 hours, cytochrome c release into the cytoplasm was markedly
      higher in KO mice than in WT mice. Caspase-3 activation was also significantly
      enhanced in KO mice versus WT mice, as evidenced by higher levels of activated
      caspase-3 and cleaved gelsolin. CONCLUSIONS: These findings suggest that the
      deletion of the hsp70.1 gene increases cytochrome c release into the cytoplasm
      and subsequent caspase-3 activation, thereby exacerbating apoptosis after focal
      cerebral ischemia.

PMID- 15243144
TI  - Poststroke neurological improvement within 7 days is associated with subsequent
      deterioration.
AB  - BACKGROUND AND PURPOSE: Improvement in the National Institutes of Health Stroke
      Scale (NIHSS) 24 hours after stroke has been associated with subsequent
      neurological deterioration. We hypothesized that a similar association would be
      apparent for events occurring after 7 days, when acute changes from edema and
      herniation are less common. We evaluated the degree of NIHSS improvement at 7
      days (recovery) as a predictor of subsequent neurological deterioration from day
      7 to day 90. METHODS: We studied all patients of the Glycine Antagonist
      (gavestinel) In Neuroprotection (GAIN) International Trial with ischemic stroke
      alive at day 7, excluding patients with hemorrhagic events and deaths from
      nonstroke-related causes. The GAIN International Trial was a randomized, double
      blind, placebo-controlled, and parallel-group trial; because the study drug had
      no effect on stroke outcome, treatment groups were combined for this analysis.
      Neurological deterioration was assessed by the combined measure, including: (1)
      stroke-related events recorded as "serious adverse events," (2) recurrent stroke
      recorded on a separate case report form, and (3) any NIHSS worsening. RESULTS:
      Among 1187 patients included, 25% had >65% recovery. Deterioration was more
      prevalent in the group with >65% early recovery (15.5% versus 10.3%; P=0.01).
      Logistic regression modeling indicated that recovery was associated with
      subsequent neurological deterioration (odds ratio, 1.2; 95% CI, 1.1 to 1.3, per
      10% recovery) after adjusting for age, NIHSS at 7 days, and stroke subtype.
      CONCLUSIONS: Substantial neurological recovery at 7 days is associated with
      subsequent neurological deterioration.

PMID- 15243145
TI  - Informed consent for thrombolytic therapy for patients with acute ischemic stroke
      treated in routine clinical practice.
AB  - BACKGROUND AND PURPOSE: Little is known about informed consent for tissue
      plasminogen activator (tPA). Our objectives were to determine how frequently
      informed consent is obtained when tPA is given to stroke patients in clinical
      practice and whether the person providing consent (patient or surrogate) was the
      appropriate decision-maker. METHODS: This retrospective cohort included acute
      stroke patients given tPA in 10 Connecticut hospitals (1996-1998). Consent was
      defined as any documentation of discussion about risks and benefits of tPA.
      Patients had adequate decision-making capacity if they were alert, oriented, and
      without aphasia or neglect (patient was appropriate decision-maker). Patients
      with any of these deficits were considered to have diminished capacity (surrogate
      was appropriate decision-maker). RESULTS: Among 63 patients who received tPA, 53
      (84%) had informed consent documented; 16/53 (30%) gave their own consent. Among
      patients with adequate decision-making capacity, 5/8 (63%) had consent by
      surrogate. Among patients with diminished capacity, 7/38 (18%) provided their own
      consent. CONCLUSIONS: A substantial percentage of patients who received tPA for
      stroke had no consent documented. Surrogates often provided consent when the
      patients had capacity; conversely, patients with diminished capacity sometimes
      provided their own consent. Given the urgency and weight of the decision
      regarding tPA, more explicit informed consent and capacity assessment should be
      considered for treatment protocols.

PMID- 15243146
TI  - Targeting neuroprotection clinical trials to ischemic stroke patients with
      potential to benefit from therapy.
AB  - BACKGROUND AND PURPOSE: Clinical trials of neuroprotective drugs have had limited
      success. We investigated whether selecting patients according to prognostic
      features would improve the statistical power of a trial to identify an
      efficacious treatment. METHODS: Using placebo data from the Glycine Antagonist in
      Neuroprotection (GAIN) International and National Institute of Neurological
      Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA)
      clinical trials, we developed and validated simple prognostic models for stroke
      trial end points: Barthel Index > or =95, modified Rankin Scale < or =1, National
      Institutes of Health Stroke Scale < or =1, and Glasgow Outcome Scale=1. Using
      these models, we simulated 1000 clinical trials and estimated, under several
      hypothetical treatment effect patterns of neuroprotection, the effect on
      statistical power of including only patients with moderate prognosis. We
      calculated the number of patients that would have to be enrolled to maintain the
      statistical power achieved in selecting the whole trial population. Reanalysis of
      actual data from the NINDS rtPA trials confirmed the results independently.
      RESULTS: Selecting patients with moderate prognosis (predicted probability of
      favorable outcome 0.2 to 0.8) enabled a sample size reduction, without loss of
      statistical power, of between 54.6% (51.3% to 57.6%) and 68.6% (66.0% to 71.1%),
      depending on the treatment effect pattern and outcome measure. These benefits
      were largely due to the exclusion of patients with poor prognosis. CONCLUSIONS:
      Targeting patients with potential to benefit enables a substantial sample size
      reduction without compromising statistical power or duration of recruitment. As
      part of a broader trial design strategy, informed use of prognostic data
      available acutely would help in identifying effective neuroprotective treatments.

PMID- 15243147
TI  - Rates and determinants of site-specific progression of carotid artery intima
      media thickness: the carotid atherosclerosis progression study.
AB  - BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) progression rates
      are increasingly used as an intermediate outcome for vascular risk. The carotid
      bifurcation (BIF) and internal carotid artery (ICA) are predilection sites for
      atherosclerosis. IMT measures from these sites may be a better estimate of
      atherosclerosis than common carotid artery (CCA) IMT. The study aim was to
      evaluate site-specific IMT progression rates and their relationships to vascular
      risk factors compared with baseline IMT measurements. METHODS: In a community
      population (n=3383), ICA-IMT, BIF-IMT, CCA-IMT, and vascular risk factors were
      evaluated at baseline and at 3-year follow-up. RESULTS: Mean (SD) IMT progression
      was significantly greater at the ICA (0.032 [0.109] mm/year) compared with the
      BIF (0.023 [0.108] mm/year) and the CCA (0.001 [0.040] mm/year) (P<0.001). Only
      ICA-IMT progression significantly correlated with baseline vascular risk factors
      (age, male gender, hypertension, diabetes, and smoking). Change in risk factor
      profile over follow-up, estimated using the Framingham risk score, was a
      predictor of IMT progression only. For all arterial sites, correlations were
      stronger, by a factor of 2 to 3, for associations with baseline IMT compared with
      IMT progression. CONCLUSIONS: Progression rates at the ICA rather than the CCA
      yield greater absolute changes in IMT and better correlations with vascular risk
      factors. Vascular risk factors correlate more strongly with baseline IMT than
      with IMT progression. Prospective data on IMT progression and incident vascular
      events are required to establish the true value of progression data as a
      surrogate measure of vascular risk.

PMID- 15243148
TI  - Increased stiffness of the carotid wall material in patients with spontaneous
      cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: The cause of spontaneous cervical artery dissection
      (sCAD) is largely unknown. An underlying connective tissue disorder has often
      been postulated, but arterial mechanical properties have rarely been studied. The
      study aim was to determine the elastic properties of a cervical artery, the
      common carotid artery, and a distal muscular artery, the radial artery in sCAD
      patients. METHODS: We studied 32 patients with previous sCAD (median delay: 2.2
      years) and 32 control subjects with similar age and blood pressure. Internal
      diameter, intima-media thickness, distensibility, and Young's elastic modulus
      were determined at the site of the right and left common carotid arteries and the
      radial artery using noninvasive high-resolution echotracking systems. RESULTS: In
      patients with previous sCAD, cross-sectional distensibility and compliance of the
      affected carotid artery did not differ from those of the contralateral carotid
      artery. Young's elastic modulus (ie, the stiffness of the wall material) was 58%
      higher (0.44+/-0.32 versus 0.28+/-0.15 kPa.10(3), P<0.001) and circumferential
      wall stress was 14% higher (56+/-12 versus 49+/-12 kPa, P<0.001) in sCAD patients
      than in controls. The highest tertile of common carotid artery Young's elastic
      modulus was associated with an 8-fold higher risk of sCAD. Aortic stiffness,
      assessed from the carotid-femoral pulse wave velocity, and radial artery
      parameters did not differ between sCAD and controls. CONCLUSIONS: Carotid
      arteries, but not aorta and radial artery, displayed abnormal elastic properties
      in sCAD patients. Higher stiffness of carotid wall material and circumferential
      wall stress could increase the risk of dissection in these patients.

PMID- 15243149
TI  - Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography:
      diagnostic performance and reproducibility of 3 different methods.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to compare diagnostic
      performance and reproducibility of 3 different methods of quantifying stenosis on
      contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial
      digital subtraction angiography (DSA) as the reference standard. METHODS: 167
      symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were
      prospectively recruited to undergo CEMRA. Severity of stenosis was measured
      according to the North American Symptomatic Trial Collaborators (NASCET),
      European Carotid Surgery Trial (ECST), and the common carotid (CC) methods.
      Measurements for each method were made for 284 vessels (142 included patients) on
      both CEMRA and DSA in a blinded and randomized manner by 3 independent attending
      neuroradiologists. RESULTS: Significant differences in prevalence of severe
      stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding
      the least and NASCET the most cases of severe stenosis. Overall, all 3 methods
      performed similarly well in terms of intermodality correlation and agreement. No
      significant differences in interobserver agreement were found on either modality.
      With CEMRA, however, we found a significantly lower sensitivity for detection of
      severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as
      reference standard. CONCLUSIONS: Uniformity of carotid stenosis measurement
      methods is desirable because patient management may otherwise differ
      substantially. All 3 methods are adequate for use with DSA. With CEMRA, however,
      this study supports use of the NASCET method because of improved sensitivity for
      detecting severe stenosis.

PMID- 15243150
TI  - Admission fibrinolytic profile is associated with symptomatic hemorrhagic
      transformation in stroke patients treated with tissue plasminogen activator.
AB  - BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (SICH) is the most
      feared complication after tissue plasminogen activator (tPA) stroke treatment.
      Endogenous fibrinolysis inhibitors play an essential role in the
      coagulation/fibrinolysis balance and may be involved in the bleeding process. We
      aim to determine the predictive value of pretreatment levels of fibrinolysis
      inhibitors (PAI-1, lipoprotein(a), TAFI, and homocysteine) on SICH. METHODS:
      Consecutive tPA-treated stroke patients with middle cerebral artery occlusion
      were studied. Baseline blood samples were obtained just before tPA administration
      and fibrinolysis inhibitors were determined. A second computed tomography (CT)
      scan was obtained at 24 hours or when a neurological worsening occurred to rule
      out SICH. RESULTS: Seventy-seven patients (40% women, age 75 years) were studied.
      Median admission National Institutes of Health Stroke Scale was 17 (range, 7 to
      22) and mean time to treatment was 160 minutes. Six patients (7.9%) presented
      with a SICH. In analyses based on clinical and CT variables, no relation could be
      found with SICH. When laboratory data were analyzed, patients who experienced
      SICH showed lower baseline PAI-1 (21.7+/-3.5 ng/mL versus 31.8+/-12.1 ng/mL;
      P<0.01) and higher TAFI (216.7+/-78.4% versus 162.1+/-54.2%; P=0.03).
      Homocysteine and lipoprotein(a) were not related to SICH. The only factors
      associated with SICH were TAFI >180% (OR, 12.9; CI, 1.41 to 118.8; P=0.02) and
      PAI-1 <21.4 ng/mL (OR, 12.75; CI, 1.17 to 139.2; P=0.04). The combination of
      admission PAI-1 <21.4 ng/mL and TAFI >180% had a sensibility of 75% and a
      specificity of 97.6% (P<0.01) predicting SICH, with a positive predictive value
      of 75% and negative predictive value of 97.6%. CONCLUSIONS: Baseline PAI-1 and
      TAFI levels predict SICH after stroke tPA therapy. In the future, these
      biomarkers could be used to improve thrombolysis safety.

PMID- 15243151
TI  - A twist in an early end.

PMID- 15243152
TI  - Spiraling toward death.

PMID- 15243153
TI  - All pain, no gain.

PMID- 15243154
TI  - Immunotherapy for Alzheimer's disease.
AB  - Strong evidence exists indicating that chronic neuroinflammation contributes to
      the progression of Alzheimer's disease (AD). A major focus of AD-associated
      research has been amyloid-beta (Abeta) protein deposits. Vaccination with Abeta
      stimulates phagocytosis of Abeta in transgenic mouse models of AD, leading to
      clearance of the deposits. Similar vaccination in humans with AD has, however,
      led to meningoencephalitis in some cases. The difference probably depends on the
      initial level of brain inflammation, which is much higher in bona fide AD in
      humans than in the transgenic mice. Because both pro- and anti-inflammatory
      activation of immune cells are possible, stimulating the phagocytic action of
      microglia while simultaneously stimulating anti-inflammatory activity might be
      beneficial in AD.

PMID- 15243155
TI  - Origins of recently gained introns in Caenorhabditis.
AB  - The genomes of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae
      both contain approximately 100,000 introns, of which >6,000 are unique to one or
      the other species. To study the origins of new introns, we used a conservative
      method involving phylogenetic comparisons to animal orthologs and nematode
      paralogs to identify cases where an intron content difference between C. elegans
      and C. briggsae was caused by intron insertion rather than deletion. We
      identified 81 recently gained introns in C. elegans and 41 in C. briggsae. Novel
      introns have a stronger exon splice site consensus sequence than the general
      population of introns and show the same preference for phase 0 sites in codons
      over phases 1 and 2. More of the novel introns are inserted in genes that are
      expressed in the C. elegans germ line than expected by chance. Thirteen of the
      122 gained introns are in genes whose protein products function in premRNA
      processing, including three gains in the gene for spliceosomal protein SF3B1 and
      two in the nonsense-mediated decay gene smg-2. Twenty-eight novel introns have
      significant DNA sequence identity to other introns, including three that are
      similar to other introns in the same gene. All of these similarities involve
      minisatellites or palindromes in the intron sequences. Our results suggest that
      at least some of the intron gains were caused by reverse splicing of a
      preexisting intron.

PMID- 15243156
TI  - Wild chimpanzee dentition and its implications for assessing life history in
      immature hominin fossils.
AB  - Data from three African field sites on Pan troglodytes demonstrate an unambiguous
      pattern of a slower growth rate in wild vs. captive chimpanzee populations. A
      revised dental growth chronology for chimpanzees is similar to estimated timing
      of Homo erectus and therefore has implications for interpreting life history in
      hominins.

PMID- 15243157
TI  - The voltage-gated Na+ channel NaVBP has a role in motility, chemotaxis, and pH
      homeostasis of an alkaliphilic Bacillus.
AB  - The prokaryotic voltage-gated Na(+) channel, NaChBac, is one of a growing channel
      superfamily of unknown function. Here we show that Na(V)BP, the NaChBac homologue
      encoded by ncbA in alkaliphilic Bacillus pseudofirmus OF4, is a voltage-gated
      Na(+) channel potentiated by alkaline pH. Na(V)BP has roles in motility,
      chemotaxis, and pH homeostasis at high pH. Reduced motility of bacteria lacking
      functional Na(V)BP was reversed by restoration of the native channel but not by a
      mutant Na(V)BP engineered to be Ca(2+)-selective. Motile ncbA mutant cells and
      wild-type cells treated with a channel inhibitor exhibited behavior opposite to
      the wild type in response to chemoeffectors. Mutants lacking functional Na(V)BP
      were also defective in pH homeostasis in response to a sudden alkaline shift in
      external pH under conditions in which cytoplasmic [Na(+)] is limiting for this
      crucial process. The defect was exacerbated by mutation of motPS, the motility
      channel genes. We hypothesize that activation of Na(V)BP at high pH supports
      diverse physiological processes by a combination of direct and indirect effects
      on the Na(+) cycle and the chemotaxis system.

PMID- 15243158
TI  - Niche tradeoffs, neutrality, and community structure: a stochastic theory of
      resource competition, invasion, and community assembly.
AB  - Stochastic niche theory resolves many of the differences between neutral theory
      and classical tradeoff-based niche theories of resource competition and community
      structure. In stochastic niche theory, invading species become established only
      if propagules can survive stochastic mortality while growing to maturity on the
      resources left unconsumed by established species. The theory makes three
      predictions about community structure. First, stochastic niche assembly creates
      communities in which species dominate approximately equally wide "slices" of the
      habitat's spatial heterogeneity. These niche widths generate realistic
      distributions of species relative abundances for which, contrary to neutral
      theory but consistent with numerous observations, there are strong correlations
      among species traits, species abundances, and environmental conditions. Second,
      slight decreases in resource levels are predicted to cause large decreases in the
      probability that a propagule would survive to be an adult. These decreases cause
      local diversity to be limited by the inhibitory effects of resource use by
      established species on the establishment (recruitment) of potential invaders. If
      resource pulses or disturbance allowed invaders to overcome this recruitment
      limitation, many more species could indefinitely coexist. Third, the low
      invasibility of high diversity communities is predicted to result not from
      diversity per se, but from the uniformly low levels of resources that occur in
      high-diversity communities created by stochastic competitive assembly. This
      prediction provides a potential solution to the invasion paradox, which is the
      tendency for highly diverse regions to be more heavily invaded.

PMID- 15243159
TI  - Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d
      restricted T cells.
AB  - A group of T cells recognizes glycolipids presented by molecules of the CD1
      family. The CD1d-restricted natural killer T cells (NKT cells) are primarily
      considered to be self-reactive. By employing CD1d-binding and T cell assays, the
      following structural parameters for presentation by CD1d were defined for a
      number of mycobacterial and mammalian lipids: two acyl chains facilitated
      binding, and a polar head group was essential for T cell recognition. Of the
      mycobacterial lipids tested, only a phosphatidylinositol mannoside (PIM)
      fulfilled the requirements for CD1d binding and NKT cell stimulation. This PIM
      activated human and murine NKT cells via CD1d, thereby triggering antigen
      specific IFN-gamma production and cell-mediated cytotoxicity, and PIM-loaded CD1d
      tetramers identified a subpopulation of murine and human NKT cells. This
      phospholipid, therefore, represents a mycobacterial antigen recognized by T cells
      in the context of CD1d.

PMID- 15243160
TI  - GTF2IRD2 is located in the Williams-Beuren syndrome critical region 7q11.23 and
      encodes a protein with two TFII-I-like helix-loop-helix repeats.
AB  - Williams-Beuren syndrome (also known as Williams syndrome) is caused by a
      deletion of a 1.55- to 1.84-megabase region from chromosome band 7q11.23.
      GTF2IRD1 and GTF2I, located within this critical region, encode proteins of the
      TFII-I family with multiple helix-loop-helix domains known as I repeats. In the
      present work, we characterize a third member, GTF2IRD2, which has sequence and
      structural similarity to the GTF2I and GTF2IRD1 paralogs. The ORF encodes a
      protein with several features characteristic of regulatory factors, including two
      I repeats, two leucine zippers, and a single Cys-2/His-2 zinc finger. The genomic
      organization of human, baboon, rat, and mouse genes is well conserved. Our exon
      by-exon comparison has revealed that GTF2IRD2 is more closely related to GTF2I
      than to GTF2IRD1 and apparently is derived from the GTF2I sequence. The
      comparison of GTF2I and GTF2IRD2 genes revealed two distinct regions of homology,
      indicating that the helix-loop-helix domain structure of the GTF2IRD2 gene has
      been generated by two independent genomic duplications. We speculate that GTF2I
      is derived from GTF2IRD1 as a result of local duplication and the further
      evolution of its structure was associated with its functional specialization.
      Comparison of genomic sequences surrounding GTF2IRD2 genes in mice and humans
      allows refinement of the centromeric breakpoint position of the primate-specific
      inversion within the Williams-Beuren syndrome critical region.

PMID- 15243161
TI  - Obstacles to successful antiretroviral treatment of HIV-1 infection: problems &
      perspectives.
AB  - Mutations in human immunodeficiency virus type 1 (HIV-1) are a major impediment
      to successful highly active antiretroviral therapy (HAART) and the design of anti
      HIV vaccines. Although HAART has made long-term suppression of HIV a reality,
      drug resistance, drug toxicity, drug penetration, adherence to therapy, low
      levels of continued viral replication in cellular reservoirs and augmentation of
      host immune responses are some of the most important challenges that remain to be
      sorted out. Continuing viral replication in the face of HAART leads to the
      accumulation of drug resistance mutations, increase in viral loads and eventual
      disease progression. Patients who fail therapy have minimal options for their
      clinical management. Therefore, a clear understanding of the pathogenesis of drug
      resistant HIV-1, and all of the issues that influence the success of HAART is
      urgently needed. In the present article, we discuss various obstacles to HIV
      therapy, and provide perspectives relating to these issues that are critical in
      determining the success or failure of HAART.

PMID- 15243162
TI  - Immune response to Leishmania infection.
AB  - Antileishmanial immune response is shown to be host genotype dependent so that
      some inbred strains of mouse are susceptible while others are resistant. The
      resistance is conferred by T-helper type-1 (Th1) cells while the susceptibility
      is conferred by Th2 cells. Th1 cells secrete IL-2 and IFN-gamma but Th2 cells
      secrete IL-4, IL-5 and IL-10. It has been shown that IFN-gamma activates
      macrophages to express iNOS2, the enzyme catalyzing the formation of nitric
      oxide. Nitric oxide kills the intracellular amastigotes. In contrast, Th2 immune
      response limits the action of Th1 functions via IL-10 and IL-4, which deactivate
      macrophages helping intracellular parasite growth and disease progression. Being
      a parasite, Leishmania ensures its own survival by modulating host immune system
      either by inducing immunosuppression or by promoting pro-parasitic host
      functions. A detailed knowledge of this host-parasite interaction would help in
      designing prophylactic and therapeutic strategies against this infection.

PMID- 15243163
TI  - Detecting mycobacteraemia for diagnosing tuberculosis.
AB  - BACKGROUND & OBJECTIVES: In human immunodeficiency virus (HIV) infected persons
      with pulmonary tuberculosis (TB), sputum may not always show acid fast bacilli
      (AFB). Moreover, in most cases of suspected extrapulmonary TB (irrespective of
      HIV status) mycobacteria-containing material is not readily available for
      investigation. This study evaluated whether blood culture for Mycobacterium
      tuberculosis bacteraemia (mycobacteraemia) help in diagnosing TB in such cases.
      METHODS: A total of 93 consecutive subjects with a clinical diagnosis of
      tuberculosis with or without laboratory confirmation, 42 with and 38 without
      coexisting HIV infection, and 13 patients with HIV infection without clinical
      evidence of TB were enrolled. Mycobacterial blood cultures were done using lysis
      centrifugation technique followed by subculturing onto the modified Lowenstein
      Jenson medium (LJ-1) and Selective Kirchner's medium followed by subculturing
      onto the modified Lowenstein-Jenson medium (LJ-2, LJ-3). RESULTS: Of the 15
      (16.2%) subjects with evidence of mycobacteremia in 4 (26.7%) blood was the
      first/ only source of diagnosing TB. Among 80 patients with clinical diagnosis of
      TB whether supported by laboratory tests or not, 14 (17.5%) had mycobacteraemia.
      Among the 21 HIV infected patients with laboratory proven TB, 9 (43%) had
      mycobacteraemia. INTERPRETATION & CONCLUSION: Blood culture appears to be a
      useful additional test to diagnose TB in persons with HIV infection. In patients
      without HIV infection, but with clinical picture compatible with TB, blood
      culture for mycobacteraemia may occasionally help in the diagnosis. We recommend
      the use of the lysis centrifugation technique followed by direct smear of the
      sediment along with inoculation of the sediment into both modified Lowenstein
      Jenson medium and the Selective Kirchner's medium with subsequent subculturing
      onto the modified Lowenstein-Jenson medium for mycobacterial blood culture for
      detecting mycobacteraemia.

PMID- 15243164
TI  - Duration of breast-feeding in Bangladesh.
AB  - BACKGROUND & OBJECTIVES: The duration of exclusive breast-feeding in Bangladesh
      is low. Though several studies have been carried out on breast-feeding in
      Bangladesh, the factors influencing the duration of breast-feeding are not
      studied. The purpose of this study was to assess the duration of breast-feeding
      among children in Bangladesh and to study socio-economic and demographic factors
      affecting the duration. METHODS: The study included 5068 mother-child pairs,
      selected on the basis of Bangladesh Demographic Health Survey (BDHS) of 1999
      2000. The risk of giving supplementary food at different ages was estimated by
      life table survival method. Independent effects of total duration of breast
      feeding of each of the study variables were estimated by using Cox's regression
      model. RESULTS: The median duration of full breast-feeding was 3.67 months
      whereas mean and median durations of total breast-feeding was 31.3 and 30 months
      respectively. Life table analysis showed that 69.9 per cent women gave
      supplementary food to their babies before reaching six months of age. Cox's
      regression analysis revealed that women who had lived in rural areas were less
      likely to terminate breast-feeding than those living in urban areas. Women who
      had completed at least secondary education were more likely to stop breast
      feeding than less or uneducated mothers. Children born in high economic status
      families had higher risk of stopping breast-feeding compared to those in low
      economic status families. Further, the deliveries assisted by the relatives had
      lower risk of terminating breastfeeding than by the health professionals.
      INTERPRETATION & CONCLUSION: According to the study results, women with higher
      education, high economic level, lower birth interval and delivery assisted by
      health personnel had lower duration of breastfeeding. Future breast-feeding
      programme in Bangladesh should give special attention to these women since they
      breast-feed relatively shorter periods of time.

PMID- 15243165
TI  - Performance evaluation of APACHE II score for an Indian patient with respiratory
      problems.
AB  - BACKGROUND & OBJECTIVES: Realising the utility of scoring systems in mortality
      prediction of critically ill patients admitted to intensive care units (ICUs),
      studies worldwide have expressed a need to validate the Acute Physiology and
      Chronic Health Evaluation (APACHE) II score for databases of respective
      countries. Literature available in this area in the Indian context is scanty. The
      present study was undertaken to evaluate the performance of APACHE II score in
      prediction of mortality risk, as well as in determination of model validity in
      critically ill Indian patients with respiratory problems. METHODS: The study was
      prospectively carried out over 18 months at respiratory ICU of a tertiary
      Institute in New Delhi, which admitted consecutive medical (with lung ailments)
      and surgical (who had undergone any elective thoracic surgical procedure under
      general anaesthesia) patients. Based on chief indication of ICU admission, the
      medical patients were further divided into sub-groups I (respiratory) and II (non
      respiratory). APACHE II points were assigned to all patients for calculating
      their individual predicted risks of mortality. Standard mortality ratio (SMR) was
      computed with 95 per cent confidence intervals (CI). Calibration of model was
      analysed by calculating Lemeshow and Hosmer goodness of fit X(2) statistic and by
      plotting calibration curve, whereas discrimination was evaluated by calculating
      area under a receiver operating characteristic (ROC) curve. RESULTS: Of the 393
      consecutive patients admitted to respiratory ICU during the study period, 63 were
      left out on account of exclusion criteria. Mean APACHE II score of the remaining
      330 patients was 12.87+/-8.25 and range from 1 to 47. There were 287 (87%)
      survivors and 43 (13%) non-survivors, whose mean APACHE II scores, being
      respectively 11.34+/-6.75 (range 1-37) and 23.09+/-10.01 (range 5-47), were
      significantly different (P<0.01). The study had a predicted mortality of 7.9 per
      cent and an SMR value of 1.65 (95% CI from 0.4 to 3.0). Mean APACHE II score of
      those having medical ailments was significantly higher (P<0.01) than surgical
      patients. The non-respiratory sub-group had a significantly higher (P<0.01) mean
      APACHE II score than respiratory sub-group. 59 per cent of patients did not get
      APACHE II points owing to being <45 yr of age. In addition, against 10
      immunocompromised patients, 77 others did not get APACHE II points despite having
      apparently compromised immunity due to co-existence of tuberculosis (TB),
      diabetes mellitus, dual pathologies or past history of anti-TB treatment.
      Observed and predicted mortality rose with 5-point APACHE II score, but did not
      correlate for patients of any comparable group. Average ICU stay of 16 days for
      those with medical disease was significantly longer (P<0.01) than 9.5 days for
      surgical patients. APACHE II scoring system showed a poor calibration and
      discrimination ability for Indian respiratory patients. INTERPRETATION &
      CONCLUSION: Despite the rise in observed and predicted mortality with 5-point
      APACHE II score, predicted mortality did not correlate with observed mortality
      for critically ill patients admitted to an Indian respiratory ICU. The scoring
      system also showed a poor calibration as well as discrimination. The model may be
      more useful for Indian patients by lowering down the cut-off value in allotment
      of age points and by awarding the weightage to factor like co-existing
      immunocompromised state.

PMID- 15243166
TI  - Rapid discrimination between strains of beta haemolytic streptococci by intact
      cell mass spectrometry.
AB  - BACKGROUND & OBJECTIVES: Beta haemolytic streptococci belonging to Lancefield
      group A, B, C and G cause a wide spectrum of clinical diseases. Hence there is a
      need for rapid and accurate typing of these strains. The present study was
      undertaken to evaluate the use of intact cell matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for rapid
      discrimination between strains of beta haemolytic streptococci. METHODS: Colonies
      of beta haemolytic streptococci were emulsified with chemical matrix on the
      sample slide, dried and analyzed by MALDI-TOF-MS. RESULTS: The reproducibility of
      results for all groups of beta haemolytic streptococci was good and spectra
      obtained for Lancefield group A, C and G streptococci showed discrimination
      between the groups on visual comparison. A finer difference in spectrum was
      observed among group A streptococci isolated from different locations at
      different periods of time. INTERPRETATION & CONCLUSION: MALDI-TOF-MS may be a
      potential tool in discriminating between strains of beta haemolytic streptococci,
      and also in the characterisation of untypable strains of group A streptococci.

PMID- 15243167
TI  - Online visibility and availability of journals can attract authors and readers.

PMID- 15243168
TI  - Heat hyperpyrexia: time to act.

PMID- 15243169
TI  - Diagnostic relevance of detection of mycobacteraemia.

PMID- 15243170
TI  - Breast-feeding practices in South Asia.

PMID- 15243171
TI  - Equating rehabilitation outcome scales: developing common metrics.
AB  - Transparency with regard to measuring devices is one of the fundamental
      requirements for progress in science. The ability to derive comparable measures
      from different measuring devices is the cornerstone of transparency. To this end,
      progress in measuring and understanding rehabilitation outcomes requires that
      there is a method of measuring outcomes that is independent of the particular
      collection of items that is used to assess the outcomes. The purpose of this
      study is to develop a equivalence between the PECS Motor Skills and Cognition and
      Communication LifeScales with the FIM Motor Skills and Cognitive items. However,
      only the results of the Motor Skills Scale are reported here in the interest of
      brevity. This equating is based on approximately 500 simultaneous evaluations
      using bout the PECS and FIM scales on admission and discharge. The patients in
      this study were consecutive admissions to a free-standing rehabilitation hospital
      in early 1998. Patients from five diagnostic groups were included in this study,
      Brain Injury, Spinal Cord Injury, Stroke, Neuromuscular, and Musculoskeletal. The
      results indicate that it is possible to construct a common equal interval
      translation between the PECS and FIM for the two scales. Measures on the common
      metric can be based to either scale and are independent of the number of items
      completed. This use of these anchored scales will allow institutions using either
      the PECS and FIM to make direct comparisons of clinical outcomes with other
      institutions, independent of the particular outcome tool used to evaluate
      patients.

PMID- 15243172
TI  - Using Rasch models to reveal contours of teachers' knowledge.
AB  - Teachers' knowledge is usually categorised into subject matter (SMK) and
      pedagogical content knowledge (PCK). Previously, measurement instruments and
      consequent cognitive scales have been developed to assess students' and teachers'
      subject knowledge. A number of qualitative studies have explored teachers'
      pedagogical content knowledge. This study developed a means to investigate one
      aspect of PCK--teachers' awareness of their students' knowledge--using a
      combination of measurement and qualitative interpretation. We asked teachers to
      estimate on a Likert scale (and also describe qualitatively) the difficulty their
      pupils would have with test items which we had already scaled using data from
      their pupils. We then constructed, using various models, a "Teacher's collective
      Perception of Item Difficulty" (TPID) scale and contrasted this with the
      student's ability scale by comparing the two sets of item-difficulty parameters.
      The results were triangulated with qualitative data. We suggest the methodology
      is best supported by an Inverse Partial Credit Model (IPCM) but we compare the
      results across alternative Rasch models.

PMID- 15243173
TI  - Validation of scores from self-learning scales for primary students using true
      score and Rasch measurement methods.
AB  - The validation of scores from the Self-learning Scales for primary pupils is
      presented in this study. The sample for the study comprised 1253 pupils from 20
      Year-3 and 20 Year-5 classes from ten primary schools in Hong Kong. The 10-item
      Usefulness Scale is designed to measure primary pupils' attitudes toward the
      usefulness of self-learning strategies situated in ten learning contexts. The 10
      item Deployment Scale is designed to measure pupils' frequency in using the self
      learning strategies. Both scales use 3-point Likert response scale. Construct
      validity of scores from the scales for use with primary pupils is supported by
      confirmatory factor analysis and Rasch measurement. Gender and year level
      differences were identified on the Rasch person measures. Generalizability of the
      scores from the two scales across gender and year level needs to be undertaken
      with caution.

PMID- 15243174
TI  - Reporting the incidence of school violence across grade levels in the U.S. using
      the Third International Mathematics and Science Study (TIMSS).
AB  - School violence has increasingly captured public attention due to deadly school
      shootings. Controversy on school violence is demonstrated by a mixed picture of
      school safety and the lack of consensus on the definitions of violence, which
      makes comparison of findings across studies difficult. This study extended the
      application of the Rasch model to school violence research using TIMSS data. The
      results show that school violence occurred at a level much lower than the
      predictions of the measurement model. Across all grade levels the most frequently
      reported type of violence is intimidation or verbal abuse of students and the
      least frequently reported physical injury to teachers or staff.

PMID- 15243175
TI  - Pre-equating: a simulation study based on a large scale assessment model.
AB  - Although post-equating (PE) has proven to be an acceptable method in the scaling
      and equating of items and forms, there are times when the turn-around period for
      equating and converting raw scores to scale scores is so small that PE cannot be
      undertaken within the prescribed time frame. In such cases, pre-equating (PrE)
      could be considered as an acceptable alternative. Assessing the feasibility of
      using item calibrations from the item bank (as in PrE) is conditioned on the
      equivalency of the calibrations and the errors associated with it vis a vis the
      results obtained via PE. This paper creates item banks over three periods of item
      introduction into the banks and uses the Rasch model in examining data with
      respect to the recovery of item parameters, the measurement error, and the effect
      cut-points have on examinee placement in both the PrE and PE situations. Results
      indicate that PrE is a viable solution to PE provided the stability of the item
      calibrations are enhanced by using large sample sizes (perhaps as large as full
      population) in populating the item bank.

PMID- 15243176
TI  - The equivalence of three data collection methods with field test data: a FACETS
      application.
AB  - The present study demonstrated the utility of the FACETS software for evaluating
      items in the field test stage of item development for a clinical early childhood
      instrument. The research focus was the equivalence of the parent/caretaker
      interview, structured assessment, and observational methods for data collection
      for a developmental inventory for children from birth to age seven. Data for this
      study were from a field test with some missing responses. The Rasch-based
      software FACETS was used to test the equivalence of the methods of data
      collection as well as to identify items for which the methods did not provide
      equivalent information. Thirty-five items were studied from the adaptive domain,
      26 items from the communication subdomain, 34 items from the motor domain, and 31
      from the personal-social domain. When the methods were unconstrained, the overall
      test indicated that at least two of the methods were not equivalent. However,
      FACETS bias analyses with the method measures constrained to equality allowed the
      identification of a limited number of items and associated methods that were
      possibly problematic. The use of FACETS allowed test developers to focus on items
      from a field test event that were inconsistent with the targeted test development
      model.

PMID- 15243177
TI  - Rasch measurement using dichotomous scoring.
AB  - The Rasch measurement model using dichotomous scoring of item response data from
      a newly created Mobility Scale administered to elderly independent living
      individuals is presented. The dichotomous scoring model, item calibration, person
      calibration, logit scale, normative scale score, reliability, and validity are
      explained. Results indicated that additional activity statements need to be
      written and tested to improve the Mobility Scale instrument.

PMID- 15243178
TI  - (3,2)D GFT-NMR experiments for fast data collection from proteins.
AB  - High throughput structure determination of proteins will contribute to the
      success of proteomics investigations. The G-Matrix Fourier Transformation NMR
      (GFT-NMR) method significantly shortens experimental time by reducing the number
      of the dimensions of data acquisition for isotopically labeled proteins (Kim, S.
      and Szyperski, T. (2003) J. Am. Chem. Soc. 125, 1385). We demonstrate herein a
      suite of ten 3D-->2D or (3,2)D GFT-NMR experiments using (13)C/(15)N-labeled
      ubiquitin. These experiments were completed within 18 hours, representing a 4- to
      18-fold reduction in data acquisition time compared to the corresponding
      conventional 3D experiments. A subset of the GFT-NMR experiments, (3,2)D HNCO,
      HNCACB, HN(CO)CACB, and 2D (1)H-(15)N HSQC, which are necessary for backbone
      assignments, were carried out within 6 hours. To facilitate the analysis of the
      GFT-NMR spectra, we developed automated procedures for viewing and analyzing the
      GFT-NMR spectra. Our overall strategy allows (3,2)D GFT-NMR experiments to be
      readily performed and analyzed. Nevertheless, the increase in spectral overlap
      and the reduction in signal sensitivity in these fast NMR experiments presently
      limit their application to relatively small proteins.

PMID- 15243179
TI  - Experiments for correlating quaternary carbons in RNA bases.
AB  - The paper presents a set of triple-resonance two-dimensional experiments for
      correlating all quaternary carbons in RNA bases to one or more of the base
      protons. The experiments make use of either three-bond proton-carbon couplings
      and one selective INEPT step (the long-range selective HSQC experiment) to
      transfer the magnetization between a proton and the carbon of interest and back,
      or they rely on one- and/or two-bond heteronuclear (the H(CN)C and H(N)C
      experiments) or carbon-carbon (the H(C)C experiment) couplings and multiple INEPT
      transfer steps. The effect of the large one-bond carbon-carbon coupling in t(1)
      is removed by a constant time evolution or by a selective refocusing. The
      performance of the proposed approach is demonstrated on a 0.5 mM 25-mer RNA. The
      results show that the experiments are applicable to samples containing agents for
      weak molecular alignment. The design of the correlation experiments has been
      supported by ab initio calculations of scalar spin-spin couplings in the free
      bases and the AU and GC base pairs. The ab initio data reveal surprisingly high
      values of guanine (2)J(N1C5) and uracil (2)J(N3C5) couplings that are in a
      qualitative agreement with the experimental data. The sensitivity of the spin
      spin couplings to base pairing as well as the agreement with the experiment
      depend strongly on the type of nuclei involved and the number of bonds separating
      them.

PMID- 15243180
TI  - Automated evaluation of chemical shift perturbation spectra: New approaches to
      quantitative analysis of receptor-ligand interaction NMR spectra.
AB  - This paper presents new methods designed for quantitative analysis of chemical
      shift perturbation NMR spectra. The methods automatically trace the displacements
      of cross peaks between a perturbed test spectrum and the reference spectrum (or
      among a series of titration spectra), and measure the changes of chemical shifts,
      heights, and widths of the altered peaks. The methods are primary aimed at the
      (1)H-(15)N HSQC spectra of relatively small proteins (<15 kDa) assuming fast
      exchange between free and ligand-bound states on the chemical shift time scale,
      or for comparing spectra of free and fully bound states in the slow exchange
      situation. Using the (1)H-(15)N HSQC spectra from a titration experiment of the
      74-residue Pex13p SH3 domain with a Pex14p peptide ligand (14 residues, K (d)=
      approximately 40 microM), we demonstrate the scope and limits of our automatic
      peak tracing (APET) algorithm for efficient scoring of high-throughput SAR by NMR
      type HSQC spectra, and progressive peak tracing (PROPET) algorithm for detailed
      analysis of ligand titration spectra. Simulated spectra with low signal-to-noise
      ratios (S/N ranged from 20 to 1) were used to demonstrate the reliability and
      reproducibility of the results when dealing with poor quality spectra. These
      algorithms have been implemented in a new software module, FELIX-Autoscreen, for
      streamlined processing, analysis and visualization of SAR by NMR and other high
      throughput receptor/ligand interaction experiments.

PMID- 15243181
TI  - NMR spectroscopic filtration of polypeptides and proteins in complex mixtures.
AB  - Due to the inherent complexity of the natural biological environment, most
      studies on polypeptides, proteins and nucleic acids have so far been performed in
      vitro, away from physiologically relevant conditions. Nuclear magnetic resonance
      is an ideal technique to extend the in vitro analysis of simple model systems to
      the more complex biological context. This work shows how diffusion-based
      spectroscopic selection can be combined with isotopic labeling to tackle and
      optimize the NMR analysis of specific macromolecules in multicomponent mixtures.
      Typical media include cell-free systems containing overexpressed proteins,
      lysates and proteolytic mixtures. We present a few variants of diffusion-edited
      HSQC pulse sequences for the selective spectroscopic detection of protein and
      polypeptide resonances within complex mixtures containing undesired species of
      smaller molecular weight. Due to diffusion-based filtering, peak intensities of
      fast diffusing small molecules are attenuated more than peaks due to large
      molecules. The basic sequence, denoted as PFGSTE-HSQC, combines translational
      diffusion-ordering with two dimensional heteronuclear single quantum correlation
      spectroscopy. The GCSTE-HSQC and BPPSTE-HSQC sequences include bipolar gradients
      and are therefore suitable for both diffusion-based filtering and determination
      of diffusion coefficients of individual mixture components. Practical
      applications range from protein stability/folding investigations in
      physiologically relevant contexts to prescreening of tertiary fold and resonance
      assignments in structural genomics studies. A few applications of diffusion
      edited HSQC to an E. coli cell lysate containing the (15)N-labeled B domain of
      streptococcal protein G (GB1), and to a (15)N-labeled N
      acetylglycine/apomyoglobin mixture are presented. In addition, we provide
      specific guidelines for experimental setup and parameter optimization.

PMID- 15243182
TI  - Alignment of chain-like molecules.
AB  - The steric obstruction model, that describes the enhanced alignment of folded
      proteins by anisotropic medium, is extended to account for the residual dipolar
      couplings of chain-like polypeptides. The average alignment of each chain segment
      is calculated from an ensemble of conformations represented by a spatial
      probability distribution. The segmental alignment depends on chain length,
      flexibility and segment's position in the chain. Residual dipolar couplings in
      turn depend on internuclear vector directions within each fragment. The results
      of calculations and simulations explain salient features of the experimental
      data. With this insight residual dipolar couplings can be interpreted to assess
      the degree of denaturation, local structures and spatial organization of weakly
      structured proteins.

PMID- 15243183
TI  - Measurements of residual dipolar couplings in peptide inhibitors weakly aligned
      by transient binding to peptide amyloid fibrils.
AB  - In this communication, we suggest that transferred residual dipolar couplings
      (trRDCs) can be employed to restrain the structure of peptide inhibitors
      transiently binding to beta-amyloid fibrils. The effect is based on the
      spontaneous alignment of amyloid fibrils with the fibril axis parallel to the
      magnetic field. This alignment is transferred to the transiently binding peptide
      inhibitor and is reflected in the size of the trRDCs. We find that the peptide
      inhibitor adopts a beta-sheet conformation with the backbone N-H and C-H dipolar
      vectors aligned preferentially parallel and perpendicular, respectively, to the
      fibril axis.

PMID- 15243184
TI  - 1H, 15N, and 13C resonance assignments of calmodulin complexed with the
      calmodulin-binding domain of calcineurin.

PMID- 15243185
TI  - 1H, 13C and 15N resonance assignments of the third spectrin repeat of alpha
      actinin-4.

PMID- 15243186
TI  - Backbone and side chain resonance assignments of domain III of the tick-borne
      Langat flavivirus envelope protein.

PMID- 15243187
TI  - 1H, 13C and 15N backbone resonance assignments of matrilysin (MMP7) complexed
      with a sulfonamide hydroxamate-type inhibitor.

PMID- 15243188
TI  - 1H, 13C and 15N assignments of the tandem WW domains of human MAGI-1/BAP-1.

PMID- 15243189
TI  - 1H, 13C and 15N resonance assignment of Cu(I)-pseudoazurin from Alcaligenes
      faecalis S-6.

PMID- 15243190
TI  - 1H, 13C, 15N resonance assignments of the cytokine LECT2.

PMID- 15243191
TI  - Backbone resonance assignments of the 18.5 kDa isoform of murine myelin basic
      protein (MBP).

PMID- 15243192
TI  - 1H, 13C and 15N resonance assignments of human 5,10-methenyltetrahydrofolate
      synthetase.

PMID- 15243193
TI  - Resonance assignments for the 18 kDa protein CC1736 from Caulobacter crescentus.

PMID- 15243194
TI  - 1H, 15N, and 13C chemical shift assignments of the Vibrio harveyi histidine
      phosphotransferase protein LuxU.

PMID- 15243195
TI  - 1H, 15N and 13C resonance assignments of the apo Sm14-M20(C62V) protein, a mutant
      of Schistosoma mansoni Sm14.

PMID- 15243198
TI  - The health and health status of older Korean Americans at the 100-year
      anniversary of Korean immigration.
AB  - There are 28 subgroups in the Asian American Pacific Islander (AAPI) ethnic
      population. They accounted for 12.5 million persons in the year 2002 or 4.4% of
      the non-institutionalized US population (Reeves&Bennett, 2003). It is a rapidly
      growing population in the United States, particularly in Southern California. The
      Korean American population is the fifth largest ethnic group in the heterogeneous
      AAPI population. Despite their increasing numbers there lacks data regarding the
      health status and healthcare utilization of the AAPI population. The aim of this
      study is to characterize the health status and healthcare utilization of an Asian
      American ethnic group, the Korean Americans. The data are from the 2000 Korean
      American Health Survey (KAHS). This survey of 1,660 Korean Americans living in
      Los Angeles County assessed their health status and medical needs and composed
      the largest sample recruited for a health study on Korean Americans to date. For
      the study 208 Koreans Americans aged 65 and over were reported. Descriptive
      statistics were performed to illustrate the health status and needs of the Korean
      American older persons. Over one-half of the sample, 69% of the Korean American
      older persons in the study reported a fair or poor health status. This is in
      stark contrast to a survey conducted by the Commonwealth Fund, which found that
      17% of the minorities and 30% of the Korean Americans rated their health as fair
      or poor (Commonwealth Fund, 2002). With regards to access to healthcare 21% of
      the Korean American older adults in the sample lacked health insurance and 31%
      had never visited a medical doctor within the last 12 months for a check up or
      consultation. It is felt that an individual's chance of being uninsured varies
      across the life span and that people 65 years and older have a minimal likelihood
      of being uninsured due to Medicare (IOM, 2001). However when looking at certain
      subgroups higher percentages of uninsured are revealed. One out of every three
      Koreans Americans in the US is uninsured compared to 21% of all AAPI and 14% non
      Latino whites. In California the proportion is even higher with almost half of
      all Koreans being uninsured (Brown et al. 2001). This type of discrepancy
      compounds the "Model Minority Myth" that AAPI population is a successful minority
      group and do not have barriers to health care (Chen et al. 1995). One study
      examining health services research status in the AAPI found that Korean Americans
      were one of the most understudied populations relative to their size (Andersen et
      al. 1995). Since the AAPI population and subgroups are often not included in
      health services research this results in "myths" or inaccuracies regarding their
      health. Studies of AAPI populations are needed to provide information regarding
      the health of the population, educate health care providers to assist them in the
      care of ethnic populations and seek interventions to remove health disparities in
      minority populations.

PMID- 15243197
TI  - Gender differences in economic support and well-being of older Asians.
AB  - This report provides a comprehensive analysis of gender differences in economic
      support and well-being in eight countries in Southern and Eastern Asia
      (Bangladesh, Malaysia, Indonesia, Singapore, Thailand, Vietnam, Philippines, and
      Taiwan). We examine multiple economic indicators, including sources of income,
      receipt of financial and material support, income levels, ownership of assets,
      and subjective well-being. Results show substantial variation in gender
      differences across indicators and provide an important qualification to widely
      held views concerning the globally disadvantaged position of older women. Whereas
      men tend to report higher levels of income than women, there is generally little
      gender difference in housing characteristics, asset ownership, or reports of
      subjective economic well-being. Unmarried women are economically advantaged
      compared to unmarried men in some respects, in part because they are more likely
      to be embedded in multigenerational households and receive both direct and
      indirect forms of support from family members.

PMID- 15243199
TI  - Middle-aged and older Latino American women in the patient-doctor interaction.
AB  - Latino women's views of and actual experiences in the patient-doctor interaction
      have been little explored. In focus groups with middle-aged and older Latino
      women, topics including assertiveness in the medical encounter, experiences in
      actual medical encounters, and characteristics of the "ideal" doctor were
      explored. Contrary to conceptualizations in the literature, assertiveness was
      viewed as a reciprocal process between patient and doctor, rather than the
      behavior of the patient alone. Assertiveness centered on obtaining answers to
      patient health questions. Strategies for self-advocacy were indirect, primarily
      changing doctors when dissatisfied; while strategies for advocating for family
      members were direct, primarily expressing dissatisfaction directly to medical
      staff. Undocumented immigrant status was described as limiting self-assertion and
      medical care access. Age was linked to doctor gender preferences. Middle-aged
      women preferred female doctors, while older women preferred male doctors. Across
      groups, women expressed preference for Spanish-speaking doctors, but not for
      doctors of the same ethnicity. Trustworthiness was identified by participants as
      the most important doctor characteristic, and learnable behaviors as exemplifying
      trustworthiness.

PMID- 15243200
TI  - Barriers to and unmet needs for supportive services: experiences of Asian
      American caregivers.
AB  - This study examined service barriers to and unmet needs for in-home and community
      based supportive services and identified risk factors that were related to unmet
      service needs reported by Asian American caregivers. Data were extracted from the
      Family Caregiving in the U.S. Survey, conducted by the National Alliance for
      Caregivers (NAC) and the American Association of Retired Persons (AARP) in 1997.
      The sample included 157 Asian American caregivers whose care receivers used
      supportive services in the past 12 months. Nearly one half of Asian American
      caregivers reported service barriers. The barriers they identified most often
      were related to personal issues that caregivers often felt "too proud to accept
      it" or "didn't want outsiders coming in." Other frequently reported barriers were
      related to service providers, including "service is not available," "bureaucracy
      too complex," or "can't find qualified providers." With respect to unmet service
      needs, more than one half of caregivers reported that services provided did not
      meet care receivers' needs. The service needs that caregivers most frequently
      reported as unmet were adult day care, meal services, and personal care. Results
      from a negative binomial regression analysis showed that elderly persons' chronic
      conditions, caregivers' educational attainment, and levels of informal assistance
      were significantly related to unmet service needs.

PMID- 15243201
TI  - Designer doping.

PMID- 15243202
TI  - Exercise training improves cardiac function postinfarction: special emphasis on
      recent controversies on na+/ca2+ exchanger.
AB  - Exercise training instituted after myocardial infarction improves many steps
      involved in cardiac excitation-contraction coupling. Focusing on Na/Caexchange,
      current controversies regarding whether it mediates Cainflux during an action
      potential, whether it is increased or decreased in disease models, whether
      protein kinase A alters its activity, and whether exercise training affects its
      function are reviewed. Finally, a novel target for exercise training in the heart
      is suggested.

PMID- 15243203
TI  - Glycogen synthase: key effect of exercise on insulin action.
AB  - Exercise improves insulin action in muscle, but the mechanisms are poorly
      characterized. Despite the notion that increased insulin signaling would
      accompany improved insulin sensitivity, this is not universally true. Increased
      activity or expression of other proteins seems to be more important. An increase
      in activity and expression of glycogen synthase and GLUT4 may be key to the
      effects of exercise.

PMID- 15243204
TI  - A multilevel approach to youth physical activity research.
AB  - Social environment factors are hypothesized to interact with individual-level
      factors to influence youth physical activity. Multilevel analytic approaches are
      ideal for examining the influence of the social environment on youth physical
      activity as they allow examination of research questions across multiple contexts
      and levels ( e.g., individual, family, and neighborhood levels).

PMID- 15243205
TI  - Multiple triggers for hyperthermic fatigue and exhaustion.
AB  - It has been proposed that a critical body temperature exists at which muscle
      activation is impaired through a direct effect of high brain temperature
      decreasing the central drive to exercise, but other factors may also inhibit
      performance in the heat. An integrative physiological model is presented to
      stimulate research into mechanisms of hyperthermic fatigue and exhaustion.

PMID- 15243206
TI  - Exercise training and sympathetic regulation in experimental heart failure.
AB  - In this review, we put forth the hypothesis that reduction in sympathetic outflow
      after exercise training of animals with heart failure is mediated by reductions
      in angiotensin II and in angiotensin type 1 receptors. Furthermore, we provide
      evidence that exercise training provides for an upregulation of the neuronal
      isoform of nitric oxide synthase in the central nervous system that is
      sympathoinhibitory.

PMID- 15243207
TI  - Adaptation of cardiac myocyte contractile properties to exercise training.
AB  - Recent work suggests that chronic exercise induces alterations in the contractile
      properties of cardiac myocytes. These alterations include increased sensitivity
      to activation by Ca, changes in the force-length relationship, and increased
      power output. A recently observed shift in expression of myosin light chain 1
      subunit isoforms induced by training may provide a molecular mechanism for these
      contractile alterations.

PMID- 15243208
TI  - Novel aspects of skeletal muscle glycogen and its regulation during rest and
      exercise.
AB  - Although it is often viewed as a homogenous substrate, glycogen is comprised of
      individual granules or 'glycosomes' that vary in their composition, subcellular
      localization, and metabolism. These differences result in additional levels of
      regulation allowing granules to be regulated individually or regionally within
      the cell during both rest and exercise.

PMID- 15243209
TI  - Statin policy and target populations: evidence-based or evidence-biased?

PMID- 15243210
TI  - Phenotypes, genotypes and response to statin therapy.
AB  - PURPOSE OF REVIEW: Response to statin treatment can vary widely from person to
      person as a result of inherited traits (genotype) and acquired characteristics
      such as obesity (phenotype). The aim of this review is to describe what is known
      about factors that determine a patient's response, and to offer a mechanism to
      explain how plasma triglyceride influences the nature and magnitude of lipid
      lowering on statin therapy. RECENT FINDINGS: In normotriglyceridemic individuals
      statins have little impact on the concentration of large VLDL, but as basal
      plasma triglyceride rises there is an increasing tendency for large VLDL,
      chylomicrons, chylomicron remnants and small, dense LDL to fall on treatment.
      These phenotype-dependent effects are in contrast to the phenotype-independent
      actions on IDL and LDL. Recent studies have also revealed that the principal
      mechanism by which statins lower VLDL (and LDL) in hypertriglyceridemic
      individuals is by stimulation of lipoprotein clearance. Individuals with low HDL
      cholesterol are increasingly treated with statins. The increase in this
      lipoprotein affects the subfraction distribution, with a specific increase in
      alpha1 HDL components. Polymorphism in the promoter for the ABCG8 gene has been
      linked to variations in response to statins; individuals with the rarer D19H
      genotype exhibit a greater reduction in LDL-cholesterol. Similarly, the magnitude
      of the statin-induced increase in HDL-cholesterol has been linked to a
      polymorphism in the promoter for apolipoprotein A1. SUMMARY: Statins are
      administered to a wide range of individuals on an empirical basis. Investigation
      of the phenotype and genotype influences on treatment response will allow a more
      tailored use of these drugs.

PMID- 15243211
TI  - CETP gene variation: relation to lipid parameters and cardiovascular risk.
AB  - PURPOSE OF REVIEW: Over the past decade lowering of low-density lipoprotein
      cholesterol levels has been established as the foundation for preventing coronary
      artery disease, but substantial additional risk reduction remains to be gained by
      modifying risk factors other than low-density lipoprotein-cholesterol. Raising
      high-density lipoprotein-cholesterol levels by inhibiting activity of the
      cholesteryl ester transfer protein (CETP) is a prime target. Research on
      naturally occurring variants in the CETP gene has yielded numerous insights that
      have been relevant for understanding lipoprotein metabolism, and crucial to the
      development of pharmacological CETP inhibition. RECENT FINDINGS: This review
      discusses a number of recently published studies, including a haplotype analysis
      of the CETP promoter region confirming that the -629 C-->A variant, not the TaqIB
      variant, is instrumental in determining CETP activity, as previously suggested.
      In addition, we discuss a recent meta-analysis which confirms that the I405V and
      TaqIB variants are indeed associated with lower CETP activity and higher high
      density lipoprotein-cholesterol levels. Also, we review two subanalyses of large
      randomized controlled pravastatin trials which found no evidence for a proposed
      pharmacogenetic interaction between the CETP TaqIB variant and pravastatin
      treatment. SUMMARY: The currently available evidence suggests that several
      genetic variants in the CETP gene are associated with altered CETP plasma levels
      and activity, high-density lipoprotein-cholesterol plasma levels, low-density
      lipoprotein and high-density lipoprotein particle size, and perhaps the risk of
      coronary artery disease. No evidence exists for a pharmacogenetic interaction
      between the CETP TaqIB variant and pravastatin efficacy.

PMID- 15243212
TI  - Paraoxonase 1 activity, concentration and genotype in cardiovascular disease.
AB  - PURPOSE OF REVIEW: To provide up-to-date information on the most recent advances
      in the epidemiology, biochemistry and molecular biology of the
      antiatherosclerotic enzyme paraoxonase 1. RECENT FINDINGS: Case-control and
      prospective studies published during the period covered by this review have
      indicated that paraoxonase 1 'status' (i.e. activity and/or concentration) was a
      more important coronary heart disease risk factor than the paraoxonase 1 genetic
      polymorphisms. New findings on the role of paraoxonase 1 in homocysteine
      metabolism are reviewed, as are advances in the nutritional and pharmacological
      regulation of paraoxonase 1. The recent controversy over whether paraoxonase 1 or
      platelet-activating factor acetylhydrolase is responsible for the antioxidant
      activity of high-density lipoprotein is also addressed. SUMMARY: In the light of
      recent findings, we believe that genetic epidemiological studies of the
      paraoxonase 1 polymorphisms in relation to coronary heart disease should no
      longer be undertaken unless they are very large and prospective in nature. More
      research should be undertaken to discover the biochemical mechanisms underlying
      the mode of action of paraoxonase 1 and the factors which modulate its activity
      and/or concentration. SPONSORSHIP: Bharti Mackness is funded by the International
      HDL Research Awards Programme. All authors receive research funding from the
      British Heart Foundation and Diabetes UK.

PMID- 15243213
TI  - Familial hypercholesterolemia in children.
AB  - PURPOSE OF THIS REVIEW: This review provides an update on recent advances in the
      diagnosis and management of children with familial hypercholesterolemia. RECENT
      FINDINGS: A large cross-sectional cohort study of paediatric familial
      hypercholesterolemia demonstrated that affected children had a 5-fold more rapid
      increase of carotid arterial wall intima-media thickness during childhood years
      than their affected siblings. This faster progression led to a significant
      deviation in terms of intima-media thickness from the age of 12 years and
      onwards. Low-density lipoprotein cholesterol was a strong and independent
      predictor of carotid artery intima-media thickness in these children, which
      confirms the pivotal role of low-density lipoprotein cholesterol for the
      development of atherosclerosis. In this condition lipid lowering by statin
      therapy is accompanied by carotid intima-media thickness regression in familial
      hypercholesterolemic children, which suggests that initiation of low-density
      lipoprotein cholesterol-reducing medication in childhood already can inhibit or
      possibly reduce the faster progression of atherosclerosis. Furthermore, these
      trials demonstrated that statins are safe and do not impair growth or sexual
      development in these children. Conversely, products containing plant sterols
      reduced low-density lipoprotein cholesterol levels by 14%, but did not improve
      endothelial dysfunction as assessed by flow-mediated dilatation. SUMMARY:
      Children with familial hypercholesterolemia clearly benefit from lipid-lowering
      strategies. Statins are safe agents and have been proven to reduce elevated low
      density lipoprotein cholesterol levels significantly. In addition, statins
      improve surrogate markers for atherosclerosis. Therefore these agents should
      become the pivotal therapy in children with familial hypercholesterolemia.

PMID- 15243214
TI  - Current management of severe homozygous hypercholesterolaemias.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in the management of
      patients with homozygous familial hypercholesterolaemia, autosomal recessive
      hypercholesterolaemia and familial defective apolipoprotein B. RECENT FINDINGS:
      Autosomal recessive hypercholesterolaemia has been described as a 'phenocopy' of
      homozygous familial hypercholesterolaemia. Although the clinical phenotypes are
      similar, autosomal recessive hypercholesterolaemia seems to be less severe, more
      variable within a single family, and more responsive to lipid-lowering drug
      therapy. The cardiovascular complications of premature atherosclerosis are
      delayed in some individuals and involvement of the aortic root and valve is less
      common than in homozygous familial hypercholesterolaemia. Apheresis is still the
      treatment of choice in homozygous familial hypercholesterolaemia and in autosomal
      recessive hypercholesterolaemia patients in whom maximal drug therapy does not
      achieve adequate control. In addition to the profound cholesterol-lowering
      effects of apheresis, other potentially beneficial phenomena have been
      documented: improved vascular endothelial function and haemorheology, reduction
      in lipoprotein (a) and procoagulatory status, and a decrease in adhesion
      molecules and C-reactive protein. SUMMARY: Patients with severe homozygous
      hypercholesterolaemia illustrate the natural history of atherosclerosis within a
      condensed timeframe. Effective cholesterol-lowering treatment started in early
      childhood is essential to prevent onset of life-threatening atherosclerotic
      involvement of the aortic root and valve, and the coronary arteries. Noninvasive
      methods for regular monitoring of the major sites involved in the atherosclerotic
      process are necessary in patients with no symptoms or signs of ischaemia.
      Management of patients with severe homozygous hypercholesterolaemia continues to
      be a major challenge.

PMID- 15243215
TI  - Combination therapy in the management of complex dyslipidemias.
AB  - PURPOSE OF REVIEW: Patients with dyslipidemias continue to be undertreated in
      both the primary and secondary prevention settings. Many patients have
      therapeutic needs that exceed simple reductions in low-density lipoprotein levels
      using statins. This review discusses the need for comprehensive management of all
      abnormalities in a given patient's lipoprotein profile and for the use of
      combinations of anti-lipidemic medications, when indicated. RECENT FINDINGS: The
      majority of high-risk patients with manifestations of atherosclerotic disease or
      who have a coronary artery disease risk equivalent are not meeting their various
      lipoprotein targets. There is considerable reluctance to titrate statins and to
      use combinations of anti-lipidemic medications in patients not reaching their
      various lipoprotein targets. Combinations of anti-lipidemic medications can be
      specifically tailored to address abnormalities in multiple lipoprotein fractions.
      Recent clinical trials clearly demonstrate that combination therapy is well
      tolerated and facilitates lipoprotein goal attainment. SUMMARY: Therapeutic
      approaches that incorporate the use of multiple anti-lipidemic medications should
      be more widely adopted in order to increase the number of patients able to meet
      their lipoprotein goals and to produce more substantially reduced risks for acute
      cardiovascular events.

PMID- 15243216
TI  - Applying apoB to the diagnosis and therapy of the atherogenic
      dyslipoproteinemias: a clinical diagnostic algorithm.
AB  - PURPOSE OF REVIEW: The first objective is to present the most recent evidence
      relating to the efficacy of apolipoprotein B as a diagnostic index of the risk of
      vascular disease and a therapeutic target for statin therapy. The second is to
      present a diagnostic algorithm for the apolipoprotein B100 dyslipidemias based on
      triglyceride and apoB. RECENT FINDINGS: The results from several recent
      prospective epidemiological studies demonstrate apoB to be superior to any of the
      cholesterol indices to estimate the risk of vascular disease. Similarly, the
      results of several of the major statin clinical trials demonstrate that apoB is a
      more adequate index of the adequacy of statin therapy than any of the cholesterol
      indices. Recent studies of lipoprotein subclass distribution in subjects with
      familial combined hyperlipidemia are reviewed. They demonstrate the limitations
      of the original lipid-based criteria and point to the necessity of using apoB as
      a fundamental diagnostic criterion for the disorder. A diagnostic algorithm for
      an apoB100 atherogenic dyslipoproteinemias is presented and the limitations of
      the lipid-based system described. SUMMARY: The evidence supporting the clinical
      use of apoB is solid, its measurement is standardized, and automated, inexpensive
      laboratory testing could easily be widely available. However, clinical benefit
      will only follow clinical application.

PMID- 15243217
TI  - Cardiovascular outcomes among participants with diabetes in the recent large
      statin trials.
AB  - PURPOSE OF REVIEW: Despite their increased cardiovascular risk and its continuous
      relationship with cholesterol, until recently only diabetic patients with marked
      dyslipidaemia were routinely offered lipid-lowering therapy. The secondary
      prevention statin trials led to more widespread cholesterol lowering in patients
      with coronary disease and diabetes. Here we review the results of recent
      randomized trials, which included substantial numbers of patients with diabetes
      and no vascular disease. RECENT FINDINGS: The MRC/BHF Heart Protection Study
      included 5963 participants with diabetes, of whom 2912 had no history of vascular
      disease at baseline. Patients were randomized to 40 mg simvastatin daily or
      matching placebo for 5 years, which, on average, reduced LDL by 1.0 mmol/l
      compared with placebo. Highly significant reductions of about one-quarter in
      major vascular events were seen both overall and in different types of patient
      with diabetes, including those with average and below average lipid levels.
      Recent data from the Antihypertensive and Lipid-Lowering Treatment to Prevent
      Heart Attack Trial and the Anglo-Scandinavian Cardiac Outcomes Trial support
      these findings and are consistent with these effects. SUMMARY: Good quality,
      randomized trials including substantial numbers of patients with diabetes show
      that such patients obtain the same proportional benefit as other groups studied.
      Given their increased cardiovascular risk, these findings argue for a simple
      strategy of considering routine statin therapy for patients with type 2 diabetes
      and adult patients with type 1 diabetes, irrespective of lipid levels. As generic
      statins become available this could have a greater impact on the burden of
      cardiovascular disease in diabetes than restricted and targeted therapy.

PMID- 15243218
TI  - Hyperlipidaemia and aortic valve disease.
AB  - PURPOSE OF REVIEW: Degenerative aortic valve stenosis is a common disease in the
      elderly, and traditional risk factors for atherosclerotic disease including
      hyperlipidaemia have been associated with the condition in several studies. This
      review addresses the role of the various risk factors and the potential for
      intervention. RECENT FINDINGS: The association of lipid abnormalities such as
      high lipoprotein(a) levels and the presence of the apolipoprotein E4 allele with
      aortic stenosis, as well as the presence of several inflammatory markers both in
      plasma and in surgically excised valves, suggest that the stenotic process is
      driven by many of the same factors behind atherosclerosis. The aortic valves of
      animals fed a cholesterol-rich diet exhibit many characteristics in common with
      the early stages of aortic stenosis. This opens up the potential of retarding the
      process through intervention strategies. SUMMARY: Hyperlipidaemia is associated
      with degenerative aortic valve stenosis, and the disease resembles the
      inflammatory process of atherosclerosis. Randomized controlled clinical trials
      will be needed to demonstrate the role of lipid intervention in patients with
      this condition.

PMID- 15243219
TI  - Statin therapy in the elderly.
AB  - PURPOSE OF REVIEW: The clinical efficacy and safety of statin therapy have been
      well established from a series of large-scale, randomized controlled trials.
      These trials, however, have predominantly recruited patients under the age of 70
      years. As a consequence, the use of statins in older patients has remained
      controversial. RECENT FINDINGS: The results of the first trial to look
      exclusively at the elderly--the Prospective Study of Pravastatin in the Elderly
      at Risk--have added enormously to our understanding of the use of statins in the
      elderly. These findings, together with those from the large elderly cohort within
      the Heart Protection Study and the smaller elderly subgroups within the other
      major statin trials, have forced us to re-evaluate any systematic exclusion of
      elderly patients from statin therapy. SUMMARY: The collective evidence now
      strongly supports the use of statins in the at-risk elderly population.

PMID- 15243220
TI  - Estrogens, lipoproteins, and cardiovascular risk factors: an update following the
      randomized placebo-controlled trials of hormone-replacement therapy.
AB  - PURPOSE OF REVIEW: The effects of hormone-replacement therapy on cardiovascular
      risk factors are examined. In an attempt to explain the results of recent
      randomized controlled trials in which no benefit of hormone-replacement therapy
      for postmenopausal women has been observed, RECENT FINDINGS: Changes in
      lipoproteins in response to hormone-replacement therapy have now been analysed
      for both primary and secondary prevention studies. In none of the large
      randomized controlled trials was there any effect of hormone-induced changes in
      low-density lipoprotein, high-density lipoprotein, or triglyceride on clinical
      outcome. Further detailed studies of lipoprotein metabolism have not revealed any
      adverse effect of hormone-replacement therapy. Recent analysis of the Heart
      Estrogen/Progestin-Replacement Study data suggests hormone-replacement therapy
      reduces the risk of developing diabetes. The effect of hormone-replacement
      therapy on inflammatory markers and on flow-mediated dilatation is largely
      beneficial, although the effect on flow-mediated dilatation is modulated
      according to endothelial function, which is adversely affected by known risk
      factors, including age and presence of atherosclerosis. In this respect the work
      on polymorphisms of estrogen receptor-alpha may in due course help to define
      those women who would benefit most from use of estrogen. Crucially, oral but not
      transdermal hormone-replacement therapy increases activated protein C resistance
      independently of the presence of factor V Leiden. This effect increases the risk
      of venous thromboembolic events, which is reflected in the results of a hospital
      case control study of thromboembolism. SUMMARY: Despite the outcome of the
      hormone-replacement therapy trials, recent work has confirmed the putative
      antiatherogenic effects of hormone-replacement therapy on lipoprotein metabolism.
      Metabolic differences of route of administration of estrogen, particularly on
      haemostatic variables, may explain this clinical paradox, which continues to be
      an important research area.

PMID- 15243221
TI  - Bibliography. Current world literature. Hyperlipidaemia and cardiovascular
      disease.

PMID- 15243222
TI  - Biomarkers for chronic disease.

PMID- 15243223
TI  - Vascular gene therapy: getting to know the players, avoiding the pitfalls.

PMID- 15243224
TI  - Lipid metabolism.

PMID- 15243225
TI  - The metabolic syndrome.

PMID- 15243226
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 15243227
TI  - Cardiovascular risk, the metabolic syndrome and the hypertriglyceridaemic waist.

PMID- 15243229
TI  - That's nursing! No, that's appalling.

PMID- 15243230
TI  - I'm no angel: I am a nurse--and that's enough.

PMID- 15243246
TI  - Pick a card--any card? Helping patients understand the new Medicare-approved drug
      discount cards.

PMID- 15243247
TI  - Is SARS reemerging? New cases of a global microbial threat.

PMID- 15243254
TI  - Calciphylaxis: an uncommon but potentially deadly form of skin necrosis.

PMID- 15243255
TI  - Reflections: the ice-bag incident.

PMID- 15243256
TI  - Oral complications at the end of life.

PMID- 15243258
TI  - Obstructive sleep apnea-hypopnea syndrome.

PMID- 15243260
TI  - Crisis in Darfur, Sudan.

PMID- 15243261
TI  - From Sudan to Omaha: how one community is helping African refugees find a new
      home.

PMID- 15243262
TI  - Enteral feedings: what the evidence says.

PMID- 15243264
TI  - A Medicare house call.

PMID- 15243268
TI  - Political action, anyone? Nurse members, the ANA urge more RNs to get involved at
      the local, state, and national levels.

PMID- 15243269
TI  - Perineural local anesthetic infusion.

PMID- 15243270
TI  - The evidence TRIP: a researcher helps nurses 'practice by evidence, not
      tradition'.

PMID- 15243271
TI  - Smallpox vaccination update.

PMID- 15243272
TI  - Cooling off hot flashes: uncoupling of the circadian pattern of core body
      temperature and hot flash frequency in breast cancer survivors.

PMID- 15243273
TI  - Effect of moderate-intensity exercise in alleviating menopausal symptoms.

PMID- 15243274
TI  - Hot flashes, core body temperature, and metabolic parameters in breast cancer
      survivors.
AB  - OBJECTIVE: To examine core body temperature, energy expenditure, and respiratory
      quotient among breast cancer survivors experiencing hot flashes and compare these
      data to published studies from healthy women. DESIGN: In an observational study,
      nine breast cancer survivors with daily hot flashes who met specified criteria
      spent 24 hours in a temperature- and humidity-controlled whole-room indirect
      calorimeter (ie, metabolic room). Demographic and disease/treatment information
      were obtained and the following were measured: hot flashes via sternal skin
      conductance monitoring (sampled every second); core body temperature via an
      ingested radiotelemetry pill (sampled every 10 seconds); and energy expenditure
      and respiratory quotient via a whole-room indirect calorimeter (calculated every
      minute). RESULTS: Circadian analysis of core temperature indicated wide
      variability with disrupted circadian rhythm noted in all women. Core temperature
      began to rise 20 minutes pre-flash to 7 minutes pre-flash (0.09 degrees C
      increase). Increases in energy expenditure and respiratory quotient increased
      with each hot flash. CONCLUSIONS: Findings are comparable to published data from
      healthy women and warrant replication in larger, more diverse samples of women
      treated for breast cancer.

PMID- 15243275
TI  - Effect of a yearlong, moderate-intensity exercise intervention on the occurrence
      and severity of menopause symptoms in postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of moderate-intensity exercise on the
      occurrence and severity of menopause symptoms. DESIGN: A yearlong, randomized,
      clinical trial, conducted in Seattle, WA, with 173 overweight, postmenopausal
      women not taking hormone therapy in the previous 6 months. The intervention was a
      moderate-intensity exercise intervention (n = 87) versus stretching control group
      (n = 86). Using logistic regression, odds ratios comparing exercise with controls
      were calculated at 3, 6, 9, and 12 months for menopause symptoms and their
      severity. RESULTS: There was a significant increase in hot flash severity and
      decreased risk of memory problems in exercisers versus controls over 12 months,
      although the numbers affected were small. No other significant changes in
      symptoms were observed. CONCLUSIONS: Exercise does not seem to decrease the risk
      of having menopause symptoms in overweight, postmenopausal women not taking
      hormone therapy and may increase the severity of some symptoms in a small number
      of women.

PMID- 15243276
TI  - Effects of social status and moderate alcohol consumption on mammary gland and
      endometrium of surgically postmenopausal monkeys.
AB  - OBJECTIVE: To evaluate the effects of social subordination stress and chronic
      moderate alcohol consumption on indices of breast and endometrial cancer risk.
      DESIGN: Forty-six adult, ovariectomized, cynomolgus monkeys (Macaca fascicularis)
      were trained to voluntarily drink a placebo or a two-drink/day equivalent of
      ethanol (0.5 g/kg), 5 days a week for 26 months, the latter resulting in average
      blood alcohol levels of 42 mg/100 mL. Indices of cell proliferation and sex
      steroid receptor abundance were measured. RESULTS: Compared with dominants,
      socially subordinate females had increased cell proliferation and proportions of
      glandular (P < 0.02) and epithelial tissue (P = 0.009) and less stroma (P < 0.02)
      in endometrium, and increased tissue thickness in breast (P < 0.05). There was no
      evidence of increased risk of breast or endometrial cancer with chronic moderate
      alcohol consumption, as indicated by markers of cell proliferation and sex
      steroid receptor abundance. Chronic moderate alcohol consumption did not effect
      circulating sex steroid concentrations (all P > 0.10). The adipocyte hormones
      leptin and adiponectin were correlated with indices of cell proliferation and sex
      steroid receptor abundance. CONCLUSIONS: These observations suggest that social
      status was more important than chronic moderate alcohol consumption in
      endometrial and breast biology of surgically postmenopausal females. Endogenous
      sex steroid metabolism was not significantly affected by chronic moderate alcohol
      exposure consistent with the lack of estrogen-like effects on breast and
      endometrium. Social subordination stress was associated with initial cellular
      changes that may increase endometrial cancer risk. Ovariectomized cynomolgus
      monkeys may be a useful model for the study of effects of social factors and
      obesity on breast and endometrial cancer risk.

PMID- 15243277
TI  - Effects of genistein on hot flushes in early postmenopausal women: a randomized,
      double-blind EPT- and placebo-controlled study.
AB  - OBJECTIVE: We evaluated and compared the effects of the phytoestrogen genistein,
      estrogen-progestogen therapy (EPT), and placebo on hot flushes and endometrial
      thickness in postmenopausal women. DESIGN: Ninety healthy, postmenopausal women,
      47 to 57 years of age, were randomly assigned to receive for 1 year continuous
      EPT (n = 30; 1 mg 17beta-estradiol combined with 0.5 mg norethisterone acetate),
      the phytoestrogen genistein (n = 30; 54 mg/day), or placebo (n = 30). Endometrial
      safety was evaluated by intravaginal ultrasounds at baseline, 6 and 12 months.
      RESULTS: By comparison with placebo, daily flushes reduced significantly by a
      mean of 22% (95% CI: -38 to -6.2; P < 0.01) after 3 months, by a mean of 29% (95%
      CI: -45 to -13; P < 0.001) after 6 months, and by a mean of 24% (95% CI: -43 to 
      5; P < 0.01) after 12 months of genistein treatment. Flush score decreased by a
      mean of 53% (95% CI: -79 to -26; P < 0.001) after 3 months, by a mean of 56% (95%
      CI: -83 to -28; P < 0.001) after 6 months, and by a mean of 54% (95% CI: -74 to 
      33; P < 0.001) after 12 months of EPT, as compared with placebo. No side effect
      was observed on the uterus of the participants. CONCLUSIONS: The present study
      confirms that genistein might have positive effects on hot flushes without a
      negative impact on endometrial thickness and suggests a future role of this
      phytoestrogen as a strategically therapeutic alternative in the management of
      postmenopausal symptoms.

PMID- 15243278
TI  - Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of
      postmenopausal osteoporosis.
AB  - OBJECTIVE: To compare the efficacy and tolerability of once-weekly (OW)
      alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of
      postmenopausal osteoporosis. DESIGN: This 12-month, randomized, double-blind
      study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at
      52 sites in the United States. Efficacy measurements included lumbar spine (LS),
      total hip, and trochanter bone mineral density (BMD) at 6 and 12 months,
      biochemical markers of bone turnover, and percent of women who maintained or
      gained BMD in response to treatment. The primary endpoint was percent change from
      baseline in LS BMD at 12 months. Adverse experiences were recorded to assess
      treatment safety and tolerability. RESULTS: Over 12 months, OW ALN produced a
      significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX (1.9%). The
      percentage of women with > or = 0% increase in LS BMD (ALN, 94%; RLX, 75%; P <
      0.001) and > or =3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001) were
      significantly greater with ALN than RLX. Total hip and trochanter BMD increases
      were also significantly greater (P < or =0.001) with ALN. Greater (P < 0.001)
      reductions in N-telopeptide of type I collagen and bone-specific alkaline
      phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No
      significant differences in the incidence of upper gastrointestinal or vasomotor
      adverse experiences were seen. CONCLUSION: ALN 70 mg OW produced significantly
      greater increases in spine and hip BMD and greater reductions in markers of bone
      turnover than RLX over 12 months. A greater percentage of women maintained or
      gained BMD on ALN than RLX. Both medications had similar safety and tolerability
      profiles.

PMID- 15243279
TI  - A randomized, placebo-controlled, crossover study of tibolone (Livial) on
      menopause symptoms, psychological well-being, and dyadic relationship of
      postmenopausal Chinese women and their spouses.
AB  - OBJECTIVE: To investigate the effects of 6-month treatment of tibolone on
      menopause symptoms, psychological well-being, and the dyadic relationship of
      postmenopausal Chinese women and their spouses. DESIGN: A randomized, double
      blind, crossover study was conducted in 100 postmenopausal Hong Kong Chinese
      women who received tibolone (2.5mg/day) and placebo. At baseline, 6-month and 13
      month visits, the women filled in the Greene Climacteric Scale (GCS), 12-item
      General Health Questionnaire (GHQ) and Dyadic Adjustment Scale (DAS), and their
      spouses completed GHQ and DAS. RESULTS: Both tibolone and placebo treatment were
      associated with a significant reduction in the GCS total scores after the first 6
      month interventional period (95% CI: -8.0 to -2.5 for tibolone, and -5.7 to -0.7
      for placebo). After the correction for placebo response, tibolone treatment was
      associated with a significant reduction in the GCS somatic subscore (-1.1 +/- 0.4
      for tibolone group versus 0.6 +/- 0.5 for placebo group, P < 0.05). There were no
      significant changes in the GHQ and DAS total scores of the women and their
      spouses after tibolone treatment, both with and without the correction for
      placebo response. CONCLUSIONS: Tibolone treatment had a significant beneficial
      effect on the somatic menopause symptoms but had no effect on the psychological
      well-being or marital relationship of the postmenopausal Chinese women and their
      spouses.

PMID- 15243280
TI  - Endometrial assessment in women using tibolone or placebo: 1-year randomized
      trial and 2-year observational study.
AB  - OBJECTIVE: To assess the effects of tibolone on the endometrium of postmenopausal
      women. DESIGN: A 1-year randomized, double-blind, placebo-controlled clinical
      trial and a 2-year open clinical trial. The placebo-controlled trial included 40
      participants: 20 in the placebo group and 20 in the tibolone group; in the open
      trial, 17 participants receiving tibolone were assessed over 24 months.
      Transvaginal ultrasonography was carried out to assess endometrial thickness, and
      endometrial appearance was assessed on hysteroscopy. In addition, endometrial
      samples were submitted to histological examination. The occurrence of uterine
      bleeding and other adverse effects was also assessed. RESULTS: Results suggest
      that tibolone does not exert a stimulatory effect on the endometrium: unaltered
      endometrial thickness, atrophic appearance of most endometria on hysteroscopy,
      and endometrial histology classified as atrophic, hypotrophic with incipient
      secretion, or hypotrophic with weak proliferation (one case). Tibolone was
      effective in the treatment of climacteric symptoms, and only 8.7% of the
      participants presented uterine bleeding during treatment. CONCLUSIONS: Tibolone
      seems to be an effective option for the treatment of climacteric symptoms in
      postmenopausal women, especially in women who do not want to experience uterine
      bleeding again.

PMID- 15243281
TI  - Raloxifene increases the capacity of serum to promote prostacyclin release in
      human endothelial cells: implication of COX-1 and COX-2.
AB  - OBJECTIVE: Prostacyclin is a potent vasodilator synthesized by two isoforms of
      cyclooxygenase in endothelium. The aim of this study was to investigate the
      effect of serum from postmenopausal women treated with raloxifene on prostacyclin
      production by human umbilical vein endothelial cells and on cyclooxygenases-1 and
      -2. DESIGN: Serum was collected from 21 women receiving 60 mg/day of raloxifene,
      at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were
      exposed to serum for 24 hours, and prostacyclin production was evaluated in
      supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS
      398) were used to investigate the relative contribution of each enzyme. Protein
      expression for each enzyme was determined using Western blot assays. RESULTS:
      Prostacyclin production was increased by 30% (P < or = 0.001) when serum from
      women treated for 3 and 6 months was added. SC-560 reversed prostacyclin
      production but did not change baseline values. NS-398, in turn, reduced
      prostacyclin production using sera from baseline, 3 and 6 months. Cyclooxygenases
      1 and -2 protein expression remained unaltered at each treatment step.
      CONCLUSIONS: Serum from women treated with raloxifene stimulated prostacyclin
      release from human umbilical vein endothelial cells in culture, an effect that
      seems mediated by increased cyclooxygenase-1 activity.

PMID- 15243282
TI  - The association between hormone therapy use and changes in strength and body
      composition in early postmenopausal women.
AB  - OBJECTIVE: To prospectively examine potential differences in upper- and lower
      body muscle strength, lower-body power, lean muscle mass, total body fat, intra
      abdominal fat, and energy expenditure (METS) variables in early postmenopausal
      women. Measurements were taken at baseline and 12 months. DESIGN: Prospective, 1
      year non-randomized [self-selected hormone therapy (HT) and non-HT-replaced],
      longitudinal study with participation from 136 normally active, early [14.2 +/-
      9.8 mo past menopause (51.1 +/- 3.0 y) mean age +/- SD] postmenopausal women.
      Total body fat mass, lean mass, and bone mass were assessed by dual-energy x-ray
      absorptiometry (Hologic), METS (6-mo activity recall questionnaire) upper- and
      lower-body peak force by isokinetic dynamometry (KinCom 500H, Chattex Corp.), and
      leg power by the Bassey Power Rig (Nottingham, UK). RESULTS: We observed no
      significant differences in central adipose tissue, total fat mass, lean muscle
      mass, strength, or lower limb power. However, estrogen did promote a maintenance
      affect in bone mineral density at the spine and total hip and an increase in
      greater trochanter bone mineral density (P < 0.01) in the estrogen-replaced
      group. CONCLUSION: Our findings suggest that HT does not play a role in either
      increasing or maintaining strength, lean muscle mass, lower limb power, or the
      attenuation of increases in total body or abdominal fat, at least in this group
      of postmenopausal women during the initial years of menopause

PMID- 15243283
TI  - Comparison of intranasal and transdermal estradiol on nasal mucosa in
      postmenopausal women.
AB  - OBJECTIVE: To compare nasal symptomatology and function and local concentrations
      of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide
      (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20
      postmenopausal women complaining of paradoxical nasal stuffiness before and after
      treatment with intranasal or transdermal E2. DESIGN: Twenty healthy
      postmenopausal women willing to start hormone therapy (HT) were allocated to one
      of two groups, using a computer-generated randomization list. Ten postmenopausal
      women were treated with transdermal 17beta-estradiol 50 microg daily plus
      nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group
      A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300
      microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole
      acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen
      fertile women undergoing nasal mucosa biopsy during plastic surgery were used as
      controls for the immunohistochemical evaluation (Group C). All women in groups A
      and B underwent evaluation of nasal stuffiness score, mucociliary transport time,
      rhinoscopy, and active anterior rhinomanometry at the beginning of the study and
      after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local
      concentrations of E2, ERalpha NPY were performed in groups A and B before and
      after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT
      improve nasal symptomatology and nasal mucosa appearance and reduce mean
      mucociliary transport time. The effectiveness of intranasally administered
      therapy at improving nasal function is significantly better than transdermal
      therapy. In comparison with premenopausal controls, untreated postmenopausal
      women of group A and B showed significantly decreased immunopositivity for E2,
      ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP
      and a decrease in NPY immunopositivity. Intranasal therapy was associated with a
      significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves
      nasal function and symptomatology in postmenopausal women with paradoxical nasal
      stuffiness, modulating nasal mucosa function through an action on cholinergic,
      adrenergic, and sensory peptides. Intranasally administered HT is more effective
      at improving nasal function than transdermal HT.

PMID- 15243284
TI  - Therapeutic decisions for menopause: results of the DAMES project in central
      Massachusetts.
AB  - OBJECTIVE: To investigate the factors that influence therapeutic decisions at
      menopause, particularly those related to the burden of menopause symptoms, in a
      population of women living in Massachusetts, as part of the multisite DAMES
      (Decisions At Menopause Study). DESIGN: A survey using face-to-face interviews
      with a randomly selected sample of 293 women aged 45 to 55 who are members of the
      Fallon Community Health Plan in Central Massachusetts. The instrument combined
      closed- and open-ended questions and elicited information about a number of
      health topics, including the symptoms experienced by respondents over the
      preceding month and the decisions they made regarding therapies. RESULTS: Symptom
      reporting was found to be relatively high, with more than half of the sample
      reporting hot flashes, sleep disturbances, joint pains, and headaches in the
      month preceding the survey; one third to one half of the women reported
      palpitations, night sweats, fatigue, and numbness. The highest frequency of
      symptoms occurred during perimenopause. Nearly four fifths of the women consulted
      a healthcare provider, and one fifth used hormone therapy. More than half of the
      respondents said menopause is a difficult phase, and about half found
      decisionmaking about it to be difficult. CONCLUSIONS: This study documents a
      relatively heavy burden of symptoms in a relatively healthy population and
      provides an update on earlier studies in Massachusetts.

PMID- 15243285
TI  - Serum leptin levels and body composition in postmenopausal women: effects of
      hormone therapy.
AB  - OBJECTIVE: To confirm the effect of postmenopausal hypoestrogenism and hormone
      therapy (HT) on body composition and serum leptin levels. DESIGN: Prospective,
      longitudinal study evaluating body composition (body mass index, and total and
      percent fat mass and lean mass measured at the arms, legs and trunk) with dual
      energy x-ray absorptiometry and serum leptin levels by radioimmunoassay in 44
      healthy postmenopausal women randomized to receive either no treatment (n = 22)
      or transdermal 17beta-estradiol (50 microg/day) in continuous regimen and
      nomegestrol (5 mg/day for 12 days/month) in a sequential regimen (n = 22).
      RESULTS: One year after the beginning of the study, in untreated women, total and
      trunk fat mass and percent fat were significantly increased, whereas trunk lean
      mass was significantly decreased. On the contrary, women treated with HT did not
      show any significant difference in body composition parameters. In untreated
      women, serum leptin levels were significantly increased at the end of the study
      in comparison with baseline values. Serum leptin levels at the other times
      evaluated were not significantly different from baseline values. In women treated
      with HT, serum leptin levels did not show significant changes throughout the
      study. CONCLUSIONS: Untreated postmenopausal women show an increase in total and
      percent fat mass and a centralization of fat distribution. Serum leptin levels
      parallel this increase, resulting in significantly higher levels 1 year after the
      study. Women treated with HT are protected against these changes. This may
      represent a protective mechanism against cardiovascular diseases.

PMID- 15243286
TI  - Profile of Female Sexual Function: a patient-based, international, psychometric
      instrument for the assessment of hypoactive sexual desire in oophorectomized
      women.
AB  - OBJECTIVE: The purpose of this study was to develop a self-administered, patient
      based questionnaire to assess loss of sexual desire and associated symptoms in
      postmenopausal women with hypoactive sexual desire disorder (HSDD) experiencing
      distress. DESIGN: Preliminary items and domains of sexual function were
      identified through individual and focus group interviews with postmenopausal
      women in the United States and Europe. A subset of items was selected for
      translation and further analysis. Cognitive interviews were conducted with women
      with HSDD and non-HSDD women in eight countries to ensure items would have the
      same meaning in seven languages. The resulting instrument was tested in 325
      oophorectomized women with HSDD and 255 age-matched nonoophorectomized control
      women in the United States, Canada, Europe, and Australia. RESULTS: Psychometric
      item reduction analyses resulted in 37 items organized into seven domains
      characterizing female sexual function in postmenopausal women with HSDD.
      Excellent reliability and validity of the domains of the Profile of Female Sexual
      Function (PFSF) were observed in all geographic areas tested. Statistically
      significant differences between oophorectomized women with low libido and control
      women were found for all domains and all geographic areas. CONCLUSIONS: The PFSF
      is a new instrument specifically designed for measurement of sexual desire in
      oophorectomized women with low libido. Robust psychometric properties have been
      established in a large number of geographic regions and languages, making it
      useful for assessing therapeutic change in multinational clinical trials.

PMID- 15243287
TI  - Preventing clinically evident coronary heart disease in the postmenopausal woman.
AB  - OBJECTIVE: This review summarizes data on the prevalent coronary heart disease
      risk factors of postmenopausal women and the pharmacologic and nonpharmacologic
      therapies available for preventing or treating them. DESIGN: Medline searches
      from 1966 on were used to identify manuscripts for coronary heart disease risk
      factor information, lipid levels as predictors of cardiovascular disease in
      women, non-pharmacologic therapies, side effects of statins, and lipid-lowering
      trials that included women and had myocardial infarction or coronary heart
      disease death as endpoints. RESULTS: Dyslipidemias that occur with menopause are
      particularly atherogenic and tend to cluster with other metabolic and
      nonmetabolic risk factors. Estrogen therapy, with or without progestogen, can no
      longer be recommended for primary or secondary prevention of cardiovascular
      disease in postmenopausal women. Statins have been effective in reducing
      cardiovascular-related morbidity and mortality and should be first-line therapy
      for lipid-lowering. CONCLUSIONS: A considerable number of women look to
      obstetricians-gynecologists for primary care. For postmenopausal women
      especially, primary care must include management of risk factors for coronary
      heart disease. Estrogen or estrogen plus progestin should be used only for
      symptomatic hot flashes and at the lowest dose possible. Statins should be first
      line therapy in preventive strategies for lipid-lowering.

PMID- 15243288
TI  - Prevention of osteoporosis and uterine effects in post-menopausal women taking
      raloxifene for 5 years.

PMID- 15243291
TI  - Severity of menopausal symptoms and use of both conventional and
      complementary/alternative theories.

PMID- 15243293
TI  - (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin
      8(4H)-one 1,1-dioxide (A-278637), a novel ATP-sensitive potassium channel opener:
      hemodynamic comparison to ZD-6169, WAY-133537, and nifedipine in the anesthetized
      canine.
AB  - The therapeutic utility of KATP channel opening agents (KCOs) in the treatment of
      overactive bladder may be limited by hypotension as a result of insufficient
      selectivity in vivo for bladder versus vasculature smooth muscle. Recently, we
      demonstrated that the putative uroselective KCOs, A-278637, ZD-6169, and WAY
      133537 suppress unstable bladder contraction in an in vivo pre-clinical pig model
      of detrusor instability secondary to partial outlet obstruction. In the present
      study in the anesthetized dog we targeted plasma concentrations 3-, 10-, and 30
      fold above a common index of in vivo efficacy (EC35) for suppression of unstable
      bladder contraction in pigs, to provide a comprehensive cardiovascular profile of
      these compounds. When compared at similar multiples of efficacy, dose-dependent
      reductions in SVR were greater in ZD-6169 and WAY-133537-treated animals versus A
      278637. A-278637, unlike ZD-6169 or WAY-133537, produced no effect on MAP at
      concentrations 10-fold above the EC35. At concentrations 30-fold above the EC35,
      MAP in A-278637-treated animals was reduced -11% from baseline versus -24% and 
      42% for ZD-6169 and WAY-133537. Accordingly, at plasma concentrations
      approximately 30-fold above the EC35 reflex-mediated increases in HR were modest
      for A-278637-treated animals (15% above baseline) versus ZD-6169 (22%) or WAY
      133537 (35%). Increases in both dP/dt and cardiac output occurred at lower
      therapeutic multiples and were greater in magnitude for animals treated with WAY
      133537 (66% and 64% above baseline, respectively, 60 minutes into compound
      infusion) and ZD-6169 (10% and 13%) versus A-278637 (-2% and 6%). Thus, A-278637
      exerted lesser effects on cardiovascular function at equivalent multiples of the
      EC35 than either ZD-6169 or WAY-133537. These data suggest that A-278637
      possesses a greater functional selectivity for urinary bladder versus vascular
      smooth muscle in vivo and that A-278637 may exhibit a more favorable therapeutic
      index than either ZD-6169 or WAY-133537.

PMID- 15243294
TI  - Sarafotoxin 6c (S6c) reduces infarct size and preserves mRNA for the ETB receptor
      in the ischemic/reperfused myocardium of anesthetized rats.
AB  - The aims of this study were to determine if the ETB receptor agonist, sarafotoxin
      6c (S6c) reduces myocardial infarct size following myocardial ischemia and
      reperfusion and to investigate whether any changes in mRNA for endothelin
      receptors in the injured myocardium were modified by S6c pretreatment.
      Hypnorm/Hypnovel anesthetized rats were subjected to occlusion of the left main
      coronary artery for 30 minutes, followed by 120 minutes reperfusion. Animals were
      administered a bolus dose of S6c (0.24 nmol kg-1 i.v., n = 10) or saline (n = 15)
      5 minutes prior to occlusion. At the end of reperfusion, hearts were stained with
      Evan's Blue dye to delineate area at risk. A 1.5- to 2.0-mm thick slice was cut
      transmurally 1 mm below the site of ligation for assessment of infarct size by
      triphenyltetrazolium chloride. A further transmural slice (2.5-3-mm thick) was
      cut for assessment of receptor mRNA levels by RTPCR. Administration of S6c caused
      a transient fall in mean arterial blood pressure (MABP) prior to occlusion and
      attenuated the fall in MABP induced by coronary occlusion. S6c significantly
      reduced infarct size (13 +/- 4% of area of slice at risk) compared with control
      hearts (35 +/- 5%; P < 0.05). In control hearts, there was a marked reduction in
      mRNA content for both ETA (50% reduction) and ETB (70% reduction) receptors in
      the ischemic zone, compared with non-ischemic tissue. In hearts pre-treated with
      S6c there was a reduction in ETA, but not ETB receptor mRNA in the ischemic zone.
      This study has shown that S6c reduces myocardial infarct size and results in
      preservation of ETB receptor mRNA in ischemic/reperfused tissue.

PMID- 15243295
TI  - Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated
      with an increase in calmodulin and a decrease in caveolin-1.
AB  - Isoflavones, such as daidzein, are proposed to possess vasculoprotective
      properties, perhaps through a mechanism similar to estrogen. Our experiments
      aimed to test the hypothesis that daidzein and 17 beta-estradiol enhance
      endothelium-dependent relaxation through an increase in NO synthesis due to an
      increase in activity or expression of endothelial nitric oxide synthase (eNOS).
      Male rats were treated with daidzein (0.2 mg/kg per day sc), 17 beta-estradiol
      (0.1 mg/kg per day sc), or vehicle for 7 days and reactivity of isolated aortic
      rings was then determined. ACh-induced relaxation was significantly enhanced in
      aortic rings from rats treated with daidzein or 17 beta-estradiol but the
      relaxant responses to the endothelium-independent dilators sodium nitroprusside
      or isoprenaline were not different. Nitrite production and the level of cGMP were
      significantly greater in aortae from daidzein and 17 beta-estradiol compared with
      vehicle-treated rats. Daidzein and 17 beta-estradiol did not alter eNOS protein
      in endothelium-intact aortae but reduced expression of caveolin-1 and increased
      expression of calmodulin, changes that would account for an increase in eNOS
      activity. There were no differences between groups in the expression of
      calmodulin and caveolin-1 in arteries when the endothelium was removed. Daidzein
      or 17 beta-estradiol treatment selectively enhances endothelium-dependent
      relaxation in male rats through an increase in eNOS activity. The increase in
      eNOS activity is associated with a decreased expression of caveolin-1 and an
      increased expression of calmodulin in endothelial cells.

PMID- 15243296
TI  - The relationship between flow-mediated brachial artery vasodilation and coronary
      vasomotor responses to bradykinin: comparison with those to acetylcholine.
AB  - Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment
      of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an
      agent for estimating coronary endothelial function. In contrast to ACh, there is
      no evidence for a relationship between FMD and coronary vasodilation to
      bradykinin (BK). The aim of this study was to compare the flow-mediated
      vasodilation of brachial artery with coronary vasomotor responses to
      intracoronary ACh or BK in patients with an angiographically normal left anterior
      descending coronary artery. Ninety-one patients underwent the cardiac
      catheterization examination with coronary endothelial function testing and the
      brachial ultrasound study. BK (0.2, 0.6, 2.0 microg/min) and ACh (3, 10, 30
      microg/min) were administered into the left coronary artery in a stepwise manner.
      Coronary blood flow was evaluated by the Doppler flow velocity measurement.
      Coronary diameters were measured by the quantitative coronary angiography. The
      assessment of endothelial function in the brachial artery was made in response to
      reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose
      dependent increases in epicardial coronary diameter and blood flow. There was a
      significant positive correlation between FMD- and BK-induced vasodilations of
      epicardial coronary arteries (0.2 microg/min: r = 0.30; 0.6 microg/min: r = 0.42;
      2.0 microg/min: r = 0.44, P < 0.01, respectively) and resistance coronary
      arteries (0.2 microg/min: r = 0.40; 0.6 microg/min: r = 0.56; 2.0 microg/min: r =
      0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of
      resistance but not epicardial coronary arteries. No correlation was seen between
      nitroglycerin-induced brachial artery vasodilation and BK-induced coronary
      vasodilation. The endothelial dysfunction of peripheral arteries correlated well
      with that of the coronary arteries especially vasomotor responses to BK.

PMID- 15243297
TI  - Characterization of purine receptors in mouse thoracic aorta.
AB  - The contracting and relaxing effects of purines and UTP were investigated on
      rings of mouse thoracic aorta in vitro. UTP, ATP gamma S, and alpha-beta
      Methyleneadenosine 5'triphosphate contracted rings with and without endothelium.
      On the contrary, adenosine, AMP, ADP, ATP, and 2-(methylthio)adenosine 5'
      diphosphate had no effect on relaxed rings. When rings were tonically contracted
      by U46619 a thromboxane A2 analogue, ATP, ADP, ATP gamma S, 2
      (methylthio)adenosine 5'-diphosphate, and UTP caused endothelium-dependent but
      not independent relaxations.I conclude that ATP acts on P2Y2 and P2Y1 receptors
      on the endothelial cells to cause endothelium-dependent relaxation. In this
      tissue, the relaxing effect of ATP dominates by endothelium-dependent ways when
      aorta rings are contracted by a stable thromboxane A2 analog. However receptors
      mediating contraction in response to purines and pyrimidines are present on
      smooth muscle cells. Indeed, the stimulation of P2Y receptors by UTP as well as
      the activation of P2X family receptors by ATP gamma S causes a contraction. The
      potential contractile effect of ATP seems masked by its hydrolysis by
      ectonucleotidases.

PMID- 15243298
TI  - Investigations on the pharmacology of the cardioprotective guanidine ME10092.
AB  - The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)
      guanidine), which possesses a strong cardioprotective effect to ischemia
      reperfusion, was assessed for different pharmacological actions that may underlie
      its cardioprotective effect. In the living rat ME10092 decreased the blood
      pressure and heart rate in a dose-dependent manner. We found ME10092 to bind to
      alpha 1- and alpha 2-adrenoreceptors with moderate affinity (Ki values 1-4
      microM), and to block adrenaline-elicited contractile responses in isolated
      guinea pig aortas. Our results indicate that ME10092 possesses a certain anti
      oxidant profile. Thus, in a competitive manner and with low affinity it inhibited
      the bovine milk xanthine oxidase enzyme, as well as NAD(P)H oxidase driven
      oxyradical formation in membrane fractions isolated from the rat brain. By using
      electron paramagnetic resonance we here show that, after its systemic
      administration, ME10092 modulates the nitric oxide (NO) content in several
      tissues of the rat in a time-dependent manner. However, in vitro ME10092
      inhibited the activities of nitric oxide synthases nNOS and eNOS, but not that of
      iNOS. Our data give evidence that the cardioprotective effect of ME10092 could be
      mediated through pharmacological mechanisms that include some modulation of NO
      production, as well as possible inhibition of radical formation during ischemia
      reperfusion.

PMID- 15243299
TI  - Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline
      induced pulmonary hypertension.
AB  - The functional roles of endothelin ETA and ETB receptors in the development of
      monocrotaline (MCT)-induced pulmonary hypertension were investigated using MCT
      treated rats in the absence or presence of a daily administration of A-192621, a
      selective ETB receptor antagonist, ABT-627, a selective ETA receptor antagonist,
      or a combination of both drugs. Four weeks after the injection of saline or MCT
      (60 mg/kg, s.c.), cardiac hypertrophy, right ventricular systolic pressure and
      morphologic changes of pulmonary arteries were evaluated. Compared with the
      control animals, MCT produced marked pulmonary hypertension associated with
      increases in right ventricular pressure and hypertrophy, and pulmonary arterial
      medial thickening. These MCT-induced alterations were markedly suppressed by
      daily treatment with ABT-627 for 4 weeks (10 mg/kg/d, twice daily), whereas
      treatment with A-192621 significantly aggravated the above MCT-induced pathologic
      changes. The blockade of both receptor subtypes by a combination of A-192621 and
      ABT-627 also significantly improved the MCT-induced pathologic changes, to the
      same extent as with ABT-627 administration. Thus, an exaggerated response to MCT
      during ETB receptor blockade also seems to be mediated by ETA receptor
      activation, thereby suggesting that ETA receptor-mediated action is exclusively
      contributive to the pathogenesis of MCT-induced pulmonary hypertension, although
      we cannot rule out a protective role of ETB receptor-mediated action.

PMID- 15243300
TI  - Antagonism by ranolazine of the pro-arrhythmic effects of increasing late INa in
      guinea pig ventricular myocytes.
AB  - The new anti-anginal drug ranolazine causes a slight (<10 milliseconds)
      prolongation of the QT interval, raising the concern that its use may be
      associated with an increased incidence of torsades de pointes ventricular
      tachyarrhythmias. The goal of this study was to show that ranolazine inhibits the
      late component of INa and attenuates prolongation of action potential duration
      when late INa is increased, both in the absence and presence of IK-blocking
      drugs. Currents and action potentials of guinea pig isolated ventricular myocytes
      were measured by whole-cell patch clamp. Sea anemone toxin (ATX)-II was used to
      increase late INa and mimic the effect of an SCN5A gene mutation. ATX-II (3-5
      nmol/L) increased late INa by 5-fold; ranolazine attenuated this increase of late
      INa by up to 61 +/- 8%. ATX-II (10-20 nmol/L) increased action potential duration
      (APD) by > 1 seconds, and caused early afterdepolarizations; both actions were
      attenuated by ranolazine (0.1-30 micromol/L). Ranolazine (10 micromol/L) reduced
      by 89% the 13.6-fold increase in variability of APD caused by 10 nmol/L ATX-II.
      The effects of ATX-II (3 nmol/L) in combinations with either the IKr blocker E
      4031 or the IKs blocker chromanol 293B to increase APD were attenuated 76 +/- 5%
      and 71 +/- 4%, respectively, by 10 micromol/L ranolazine. The results demonstrate
      that ranolazine reduces late INa and has an anti-arrhythmic effect when late INa
      is increased.

PMID- 15243301
TI  - Differential calcium regulation by hydrogen peroxide and superoxide in vascular
      smooth muscle cells from spontaneously hypertensive rats.
AB  - We investigated the role of reactive oxygen species (ROS), particularly hydrogen
      peroxide (H2O2) and superoxide anion (*O2-) in the regulation of vascular smooth
      muscle cell (VSMC) Ca2+ concentration ([Ca2+]i) and vascular contraction and
      assessed whether redox-dependent Ca2+ signaling and contraction are altered in
      hypertension. VSMCs and mesenteric arteries from Wistar Kyoto (WKY) and
      spontaneously hypertensive rats (SHR) were studied. Cells were stimulated with
      H2O2 (10(-4) mol/l) or LY83583 (*O2- generator, 10(-5) mol/l). [Ca2+]i and
      cytosolic *O2- were measured by fura-2AM and tempo-9-AC fluorescence
      respectively. L-type and T-type Ca2+ channels were assessed using
      verapamil/diltiazem and mibefradil respectively and mRNA and protein expression
      of these channels was assessed by real-time PCR and immunoblotting respectively.
      H2O2 time-dependently increased [Ca2+]i and contraction with significantly
      greater effects in SHR versus WKY (P < 0.001). LY83583 increased [Ca2+]i in both
      strains, but responses were blunted in SHR. Removal of extracellular Ca2+
      abrogated [Ca2+]i responses to H2O2 and *O2-. Verapamil and diltiazem, but not
      mibefradil, significantly decreased H2O2 -induced [Ca2+]i responses with greater
      effects in SHR (P < 0.01). L-type and T-type Ca2+ channel inhibition reduced
      LY83583-mediated [Ca2+]i increase only in WKY cells. Both types of Ca2+ channels
      were expressed (mRNA and protein) in VSMCs from WKY and SHR, with greater
      abundance in SHR than WKY (2- to 3-fold). These results demonstrate that ROS
      increase vascular [Ca2+]i and contraction, primarily via extracellular Ca2+
      influx. Whereas responses to H2O2 are enhanced, *O2- -mediated actions are
      blunted in SHR. These effects may relate to differential activation of Ca2+
      channels by H2O2 and *O2-. Enhanced activation of L-type Ca2+ channels and
      increased Ca2+ influx by H2O2 may contribute to increased Ca2+ signaling in VSMCs
      from SHR.

PMID- 15243302
TI  - Pharmacokinetics and steady-state bioequivalence of treprostinil sodium
      (Remodulin) administered by the intravenous and subcutaneous route to normal
      volunteers.
AB  - Treprostinil sodium is a chemically stable analogue of prostacyclin administered
      as a chronic, continuous subcutaneous infusion for the treatment of pulmonary
      arterial hypertension (PAH). There has been significant clinical interest in
      determining the feasibility of delivering treprostinil by intravenous infusion.
      Therefore, a bioequivalence and comparative pharmacokinetics study of the two
      routes of administration was conducted in normal volunteers. A randomized, two
      period, crossover study design was employed. Each subject was dosed at 10
      ng/kg/min for 72 hours by each route, with the infusions separated by a 4-day
      wash-out period. In the 51 subjects who received at least 24 hours of
      treprostinil administered subcutaneously and intravenously, the steady-state
      ratios of the geometric means (i.v./s.c.) and 90% confidence intervals for AUCss
      and Cmaxss were 92.9% (89.8-96.1%) and 106% (99.4-113%), respectively. Secondary
      pharmacokinetic assessments confirmed the comparability of the two routes of
      administration at steady state, and also demonstrated that the elimination half
      life of treprostinil was 4.4 and 4.6 hours following intravenous and subcutaneous
      administration, respectively. Based on these findings it was concluded that
      intravenously and subcutaneously administered treprostinil are bioequivalent at
      steady state.

PMID- 15243303
TI  - Rosiglitazone improves, while Glibenclamide worsens blood pressure control in
      treated hypertensive diabetic and dyslipidemic subjects via modulation of insulin
      resistance and sympathetic activity.
AB  - BACKGROUND: Type II diabetes is often associated with high blood pressure,
      elevated sympathetic activity, and high plasma insulin levels. Hypoglycemic
      agents may negatively interfere with blood pressure control, sympathetic
      activity, and plasma insulin level; therefore the choice of treatment in type II
      diabetes may be crucial. We aimed to compare the effects of two hypoglycemic
      drugs on blood glucose, blood pressure, sympathetic activity, and insulin levels
      in type II diabetic and hypertensive patients. METHODS: Forty-eight (24M, 24F)
      type II diabetic, hypertensive, and hyperlipidemic subjects were enrolled and
      treated for 4 weeks with an ACE inhibitor (Cilazapril) and a statin
      (Simvastatin). They were then randomized into two groups to receive a
      thiazolidinedione (Rosiglitazone; ROS) or a sulfonylurea (Glibenclamide; GLB) for
      8 weeks. Blood biochemistry, blood pressure, plasma insulin, endothelial
      function, and sympathetic skin activity were measured before and after treatment.
      RESULTS: A significant drop in systolic and diastolic blood pressure by 6.1 +/-
      4.1 mm Hg and 4.2 +/- 1.9 mm Hg respectively; a reduction in plasma insulin
      concentration by 4.3 +/- 1.9 mU/L and a decline in skin sympathetic activity were
      observed in the group receiving ROS. The GLB group showed an increase in systolic
      blood pressure by 3.1 +/- 2.5 mm Hg, no change in diastolic blood pressure,
      significant elevation in plasma insulin concentration by 2.3 +/- 1.4 mu/L, and
      augmentation of sympathetic activity. No significant changes in endothelial
      function were observed in either group. CONCLUSIONS: Rosiglitazone improved both
      plasma glucose and blood pressure levels, probably by attenuation of
      hyperinsulinemia and sympathetic activity, while Glibenclamide worsened blood
      pressure control possibly by elevation of insulin levels and activation of the
      sympathetic system.

PMID- 15243304
TI  - Different effects of calcium channel blockers on matrix metalloproteinase-2
      expression in cultured rat cardiac fibroblasts.
AB  - The cardiac effects of calcium channel blockers (CCBs) related to cardiac
      remodeling are inconsistent. Matrix metalloproteinases (MMPs) contribute to
      tissue remodeling. Cardiac fibroblasts play an important role in the regulation
      of collagen degradation by MMPs. Using gelatin zymography, Western blotting,
      Griess reagent, and a calcium kit-fluo 3, we investigated the effects of
      nifedipine, verapamil, diltiazem, and amlodipine on MMP-2 expression and further
      elucidate the mechanisms in cultured rat cardiac fibroblasts. Nifedipine
      increased and amlodipine decreased the expression of MMP-2; however, neither
      verapamil nor diltiazem altered MMP-2 expression. Nifedipine also increased
      nitrite production, and this increase was blunted by a nitric oxide (NO)
      synthases inhibitor (L-NAME). Nifedipine-induced MMP-2 expression was also
      blunted by L-NAME. An NO donor (sodium nitroprusside) induced MMP-2 expression.
      Data indicated that nifedipine might increase MMP-2 expression through a possible
      NO-dependent pathway. Amlodipine had no influence on nitrite production. The
      amlodipine-induced decrease of MMP-2 expression was abolished by two protein
      tyrosine kinase inhibitors, genistein and herbimycin A, indicating that
      amlodipine might decrease MMP-2 expression through a possible protein tyrosine
      kinase pathway. None of the four CCBs could alter the fluoscence intensity of
      fluo 3, indicating that the effects of CCBs on MMP-2 expression were independent
      of the variation in intracellular C2+ concentration. Our findings revealed that
      different CCBs exerted different effects on MMP-2 expression in cardiac
      fibroblasts.

PMID- 15243305
TI  - Pharmacodynamics of L-NMMA in type 1 diabetes patients and control subjects.
AB  - RATIONALE: L-NMMA is widely used in venous occlusion plethysmography studies to
      determine baseline NO production. Studies using L-NMMA indicate that endothelial
      dysfunction is present early in the course of diabetic microvascular
      complications. However, the optimal dose to maximally inhibit NO-production is
      unknown. OBJECTIVE: To determine the L-NMMA-dose that maximally reduces basal
      forearm blood flow (FBF). To investigate whether there are any differences in the
      response to L-NMMA between non-complicated type 1 diabetes patients and control
      subjects. METHODS: In eight non-complicated type 1 diabetes patients and nine
      healthy subjects FBF-responses to intra-arterial infusion of increasing doses of
      L-NMMA (0.01-1.6 mg/min/dL forearm volume [FAV]) were measured using the perfused
      forearm technique. RESULTS: Infusion of 0.8 mg/min/dL maximally reduced FBF. The
      dose of 1.6 mg/min/dL did not additionally reduce FBF. No differences existed
      between non-complicated type 1 diabetes patients and controls with regard to EC50
      (0.017 +/- 0.02 resp. 0.22 +/- 0.02 mg L-NMMA/min/dL) or maximal vasoconstrictive
      response (Delta FBF: 1.13 +/- 0.4 resp. 0.97 +/- 0.4 mL/min/dL). Throughout the
      study blood pressure increased significantly in both groups, possibly reflecting
      a systemic vasoconstrictive effect of L-NMMA. CONCLUSIONS: The maximal
      vasoconstrictive dose was 0.8 mg/min/dL in type 1 diabetes patients as well as
      the control subjects. There were no significant differences between non
      complicated type 1 diabetes subjects and controls with regard to the
      pharmacodynamics of L-NMMA. At high dosages of L-NMMA a systemic effect can not
      be ruled out.

PMID- 15243306
TI  - Cyclic GMP reduces myocardial stunning through non-cyclic GMP protein kinase
      mechanisms.
AB  - We tested the hypothesis that myocardial stunning would be reduced by increased
      cyclic GMP and cGMP protein kinase activity. Hearts were instrumented in eight
      open-chest anesthetized dogs. The left anterior descending coronary artery (LAD)
      was occluded for 15 minutes followed by a 30-minute recovery and infusion of 8
      Bromo-cGMP (0.1 and 1 microg/kg/min) during functional and metabolic data
      collection. Myocytes from circumflex and LAD regions were then used to obtain
      data at baseline, with 8-Br-cGMP (10(-7, -6, -5) M) and KT5823 10(-6) M, cGMP
      protein kinase inhibitor. The in vivo time delay of regional shortening increased
      significantly from 55 +/- 12 to 99 +/- 3 msec following stunning, but was reduced
      to 81 +/- 2 by 1 microg/kg/min 8-Br-cGMP. The % regional work during systole
      decreased during stunning (93 +/- 2 to 76 +/- 8%), but was restored by 8-Br-cGMP
      (91 +/- 7). Stunning lengthened the time of myocyte contraction and relaxation
      and reduced baseline shortening. 8-Br-cGMP reduced myocyte shortening in both
      regions. However, KT5823 only restored myocyte shortening in controls. These data
      indicated that regional myocardial stunning could be reduced by cyclic GMP but
      this appeared to be through non-cGMP protein kinase mechanisms.

PMID- 15243307
TI  - In vivo and in vitro characterization of the novel antiarrhythmic agent
      SSR149744C: electrophysiological, anti-adrenergic, and anti-angiotensin II
      effects.
AB  - SSR149744C (SSR, 2-butyl-3-[4-[3-(dibutylamino)pro-pyl]benzoyl]-1-benzofuran-5
      carboxylate isopropyl fumarate), is a new non-iodinated benzofuran derivative.
      The aim of this study was to evaluate in vivo its electrophysiological,
      hemodynamic, and anti-adrenergic properties and to determine its mechanism of
      action using in vitro studies. In chloralose-anesthetized dogs, SSR149744C (1-10
      mg/kg i.v.) prolonged the sinus cycle length, A-H interval, Wenckebach cycle
      length, atrial effective refractory period (ERP), and atrio-ventricular node ERP
      in a dose-dependent manner without change of ventricular ERP and HV, QRS, or QTc
      intervals. Arterial blood pressure and ventricular inotropism were slightly
      decreased. SSR149744C, which has no or low affinity for alpha 1 and beta 1
      adrenergic and angiotensin II AT1 receptors, reduced isoproterenol-induced
      tachycardia and phenylephrine- or angiotensin II-induced hypertension in
      anaesthetized dogs. In guinea pig papillary muscle, SSR149744C did not modify the
      resting potential, action potential amplitude and duration, but reduced the dV/dt
      max of the depolarization phase in a frequency-dependent manner. In isolated
      guinea pig cardiomyocytes and transfected CHO cells, SSR149744C (0.01-30 microM)
      inhibited several potassium currents: IKr (IC50 approximately 10 microM), IKs
      (IC50 approximately 30 microM), IK(ACh) (IC50 = 0.09 microM), and IKv1.5 (IC50 =
      2.7 microM), the L-type calcium current: ICa(L) (IC50 approximately 5 microM) and
      also the amplitude of [Ca2+]i transient and cell shortening. Therefore,
      SSR149744C appears to have a multifactorial mechanism of action, which combines
      the blockade of several ion channels with the inhibition of responses of alpha 1
      and beta 1 adrenergic as well as AT1 receptor stimulation. Like amiodarone,
      SSR149744C possesses the pharmacological effects of class I, II, III, and IV
      antiarrhythmic agents, which may confer upon this new drug a strong
      antiarrhythmic potential without ventricular proarrhythmia and iodine-related
      amiodarone-like side-effects.

PMID- 15243308
TI  - Vasopeptidase inhibition improves insulin sensitivity and endothelial function in
      the JCR:LA-cp rat.
AB  - The insulin-resistant, hyperinsulinemic, normoglycemic, and obese JCR:LA-cp rat
      was used to study the effects of ramipril (an ACE inhibitor) and AVE7688 (a dual
      inhibitor of ACE and neutral endopeptidases) on insulin sensitivity and vascular
      function. Both compounds reduced the surge of plasma insulin in a meal tolerance
      test by approximately 50%. Ramipril had no effect on acetylcholine-induced
      relaxation but increased the sensitivity to sodium nitroprus-side at low
      concentrations. AVE7688 significantly reduced the EC50 for acetylcholine to relax
      phenylephrine-contracted aortic rings. None of the compounds affected the
      baseline coronary flow and reactive hyperemia. Coronary flow response to
      bradykinin in AVE7688- and ramipril-treated rat hearts showed a significantly
      lower EC50 than in control rats. Maximum flow rate was not different between
      groups. In summary, both ramipril and AVE7688 had significant hypoinsulinemic and
      insulin-sensitizing effects. Whereas ramipril had limited vascular effects,
      AVE7688 had more marked beneficial vascular effects, probably of endothelial
      origin and possibly related to lowered insulin levels.

PMID- 15243310
TI  - Treatment of kidney disease and anemia in elderly, long-term care residents.

PMID- 15243309
TI  - Cilostazol and dipyridamole synergistically inhibit human platelet aggregation.
AB  - It has been previously shown that cilostazol (Pletal), a drug for relief of
      symptoms of intermittent claudication, potently inhibits cyclic nucleotide
      phosphodiesterase type 3 (PDE3) and moderately inhibits adenosine uptake. It
      elevates extracellular adenosine concentration, by inhibiting adenosine uptake,
      and combines with PDE3 inhibition to augment inhibition of platelet aggregation
      and vasodilation while attenuating positive chronotropic and inotropic effects on
      the heart. In the present study, we tested the hypothesis that cilostazol
      combined with a more potent adenosine uptake inhibitor, dipyridamole,
      synergistically inhibited platelet aggregation in human blood. In the presence of
      exogenous adenosine (1 microM), the combination of cilostazol and dipyridamole
      synergistically increased intra-platelet cAMP. Furthermore, cilostazol inhibited
      platelet aggregation in a washed platelet assay concentration-dependently with
      IC50s of 0.17 +/- 0.04 microM (P < 0.05 versus plus adenosine alone of 0.38 +/-
      0.05 microM), 0.11 +/- 0.06 microM (P < 0.05), and 0.01 +/- 0.01 microM (P <
      0.005) when combined with 1, 3, or 10 microM dipyridamole, respectively (n = 5).
      In whole blood, cilostazol (0.3 to 3 microM) and dipyridamole (1 or 3 microM)
      synergistically inhibited collagen- and ADP-induced platelet aggregation in
      vitro. Furthermore, the synergism was confirmed in an open-label, sequential
      study in healthy human subjects using ex vivo whole-blood collagen-induced
      platelet aggregation. Four hours after oral co-administration of cilostazol (100
      mg) and dipyridamole (200 mg), platelet aggregation was inhibited by 45 +/- 17%,
      while no significant inhibition was observed from subjects treated with either
      drug alone. The combination may provide a potential treatment of arterial
      thrombotic disorders.

PMID- 15243311
TI  - Recognizing and responding to atypical antipsychotic side effects.

PMID- 15243312
TI  - Avoiding malpractice: the role of proper nutrition and wound management.

PMID- 15243313
TI  - AMDA's top 10 policy issues for 2004.

PMID- 15243314
TI  - [Colorectal cancer and hepatic synchronous metastases: should the primary tumor
      be resected].

PMID- 15243315
TI  - Colorectal cancer with non-resectable synchronous metastases: should the primary
      tumor be resected?
AB  - OBJECTIVES: In asymptomatic patients presenting with non-resectable synchronous
      metastatic disease from colorectal adenocarcinoma, the beneficial effect of
      resecting the primary tumor remains to be documented. The aim of this study was
      to compare survival of patients with metastatic colorectal cancer who underwent
      elective resection of the primary tumor to those who did not. METHODS: A
      retrospective analysis of patients with metastatic colo-rectal cancer treated
      between June, 1996 and December, 1999 was performed. Overall survival was
      compared between patients who underwent first-line resection of the primary
      colorectal tumor (group 1) or those who did not undergo elective resection of the
      primary (group 2). The probability of surgical resection of the primary tumor for
      gastrointestinal complications in group 2 was evaluated. RESULTS: Thirty-one and
      23 patients were included in groups 1 and 2 respectively. Five patients (21.7%,
      95% confidence interval CI95% 4.9-38.5%) in group 2 required surgical treatment
      for intestinal obstruction due to the primary tumor. Two clinical characteristics
      were significantly different between groups 1 and 2: rectal localization (9.7%
      versus 34.7%; P=0.03) and presence of fewer than three metastases (29.0% versus
      4.3%; P=0.03). Survival curves were not significantly different (logrank). Median
      duration of survival was 21 and 14 Months, respectively (P=0.718). CONCLUSION: In
      patients with non-resectable synchronous metastatic disease, non-surgical
      management of the primary tumor is a rational alternative if asymptomatic. A
      prospective randomized trial integrating the quality-of-life factor should be
      organized.

PMID- 15243316
TI  - Effect of an oral bulking agent and a rectal laxative administered alone or in
      combination for the treatment of constipation.
AB  - OBJECTIVES: The aim of the present study was to search for a synergetic action
      between psyllium and a defecation-inducing drug, Eductyl, for symptom relief in
      patients suffering from chronic constipation. METHODS: Twenty healthy volunteers
      and 20 patients complaining of chronic constipation were included in a randomized
      crossover study. The study was divided into four 2-weeks periods: pre-inclusion
      and three periods of treatment with psyllium, Eductyl, and Eductyl + psyllium
      respectively. Colonic transit time was determined at the end of each period of
      treatment. During each of the four periods, a self-administered questionnaire was
      used to assess symptoms of constipation. RESULTS: For constipated patients,
      treatment with Eductyl and Eductyl-psyllium improved clinical symptoms of
      constipation: increased stool frequency, resulted in fewer hard stools and less
      sensation of incomplete evacuation and less straining to defecate. The
      improvement was associated with a decrease in total and segmental colonic transit
      time. The Eductyl-psyllium combination did not exhibit any synergetic effect.
      CONCLUSION: Treatment with Eductyl alone is more efficient than with psyllium
      alone in providing symptom relief. Combination with psyllium is not synergetic.

PMID- 15243317
TI  - [Gastric permeability and Helicobacter pylori].

PMID- 15243318
TI  - [Hepatitis C from body piercing: fashion phenomenon or a public heath problem?].

PMID- 15243319
TI  - [Economic assessment of HCV screening: make no mistake about your indicators!].

PMID- 15243320
TI  - [Fibrotest: epistemological evolution and ethical breakthrough].

PMID- 15243321
TI  - Isotopic exploration of hepatic hydrothorax: ten cases.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the performance of
      peritoneal scintigraphy for the diagnosis of peritoneopleural communication in
      patients with cirrhosis and to discuss its role in therapeutic management.
      PATIENTS AND METHODS: Ten patients with cirrhosis and pleural effusion were
      included in this study. Cirrhosis was due to viral hepatitis in eight patients,
      auto-immune disease in one patient and of unknown origin in one. The pleural
      effusion was right-sided in nine patients and bilateral in one. 99m-technetium
      sulfur colloid peritoneal scintigraphy was performed in all patients. RESULTS:
      Scintigraphy revealed peritoneopleural communication in nine patients. In four
      patients, radioactivity appeared in the pleural cavity within a few minutes after
      injection of the radiotracer. In three of them, a large diaphragmatic defect was
      demonstrated by ultrasonography, magnetic resonance imaging or thoracoscopy.
      Complete response to medical treatment was observed in four patients.
      Scintigraphy revealed rapid radioactivity migration in four patients; diuretic
      treatment led to resolution of the hydrothorax in one of them. Three patients
      whose hydrothorax was refractory to medical treatment were treated by pleurodesis
      with talc. Resolution of the hydrothorax was achieved in one of them. CONCLUSION:
      Peritoneal scintigraphy is a simple non-invasive method enabling confirmation of
      peritoneopleural communication in cirrhotic patients. The importance of the
      diaphragmatic defect can also be evaluated, providing a significant contribution
      to therapeutic decision-making.

PMID- 15243323
TI  - [Bacterial liver abscess].

PMID- 15243324
TI  - [Bacterial liver abscess].

PMID- 15243325
TI  - [Liver bacterial radiologist view point on bacterial liver abscess: from
      diagnosis to treatment].

PMID- 15243327
TI  - [Esophageal sarcomatoid carcinoma: report of a case with morphological,
      immunohistochemical and molecular study].
AB  - Sarcomatoid carcinoma is a rare tumor of the esophagus, characterized
      macroscopically by a polypoid aspect and histologically by the association of
      spindle cell carcinoma with sarcomatous pleomorphic component. We report here a
      case of esophagus sarcomatoid carcinoma. Diagnosis was based on
      immunohistochemical analysis of tIssue samples. Human papillomavirus (HVP)
      detection by PCR amplification of DNA extracted from tumoral tIssue was negative,
      ruling out the role of HPV infection in this tumor.

PMID- 15243328
TI  - [Gastric metastasis from ovarian carcinoma revealed by a gastro-splenic
      perforation].
AB  - Metastatic disease involving the stomach is unusual. We report the case of a
      gastric metastasis from ovarian cancer revealed by gastro-splenic perforation.
      The gastric metastasis was diagnosed 17 years after the diagnosis of primary
      cancer.

PMID- 15243329
TI  - [Periampullar gangliocytic paraganglioma resected by surgical ampullectomy: a
      case report].
AB  - We report the case of a 40-Year-old woman with duodenal gangliocytic
      paraganglioma of the ampulla of Vater. Preoperative diagnosis was periampullar
      tumor. Final diagnosis of duodenal gangliocytic paragangioma of the ampulla of
      Vater with negative margins was made by histological and immunohistochemical
      study of surgical ampullectomy specimen. This case report stresses the yield of
      immunohostochemical study in the diagnosis of duodenal gangliocytic
      paraganglioma, a rare entity.

PMID- 15243330
TI  - [Hepatocellular carcinoma without cirrhosis in a patient with nonalcoholic
      steatohepatitis].
AB  - All cases of hepatocellular carcinoma reported thus for in patients with
      nonalcoholic steatohepatitis have occurred on preexisting cirrhosis. We report
      the case of a 68-Year-old male patient with nonalcoholic steatohepatitis who
      developed hepatocellular carcinoma in the absence of cirrhosis. This observation
      suggests a possible relationship between nonalcoholic steatohepatitis and/or
      excess body weight, and hepatocellular carcinoma independent of cirrhosis.
      Further epidemiological studies are needed to evaluate the incidence of this
      association.

PMID- 15243331
TI  - [Chronic diarrhea induced by Cryptosporidium parvum in an immunocompetent adult:
      difficult diagnosis and unsatisfactory treatment].

PMID- 15243332
TI  - [Bone marrow aplasia following dipyrone treatment in a patient with Crohn's
      disease receiving long-term methotrexate].

PMID- 15243333
TI  - [Mumps acute pancreatitis in an elderly patient].

PMID- 15243334
TI  - [Amoxicillin induced acute hepatitis].

PMID- 15243335
TI  - [Cytolytic hepatitis induced by darbepoetin alpha treatment].

PMID- 15243336
TI  - [Hepatitis C virus from ear piercing].

PMID- 15243337
TI  - [5-aminosalicylates and colorectal cancer: preventive role in chronic
      inflammatory bowel disease?].

PMID- 15243338
TI  - [Hepatitis C virus and B cell lymphoma].

PMID- 15243339
TI  - [Insurance management of medical risks].

PMID- 15243340
TI  - [Evaluation of the effects of electric and magnetic fields in humans].
AB  - During the twentieth century, environmental exposure to electromagnetic fields
      generated by human activity has increased regularly, at the same time as the
      quest for electrical energy. Therefore we are all exposed to a complex set of
      electric and magnetic fields of weak intensity. The levels of exposure of the
      general population range from 5 to 50 V/m for electric fields and from 0.01 to
      0.2 micro T for magnetic fields. Fields in cause are essentially those associated
      to the use of the electric current (extremely low frequency, ELF: 50 Hz in
      France, 60 Hz in the United States) and those related to the use of cell phones
      (radio frequency: 900 and 1,800 MHz). The question of the possible risk on health
      by exposure to electric and/or magnetic fields became a concern to scientists and
      is now an important public debate. A number of expertises, led in particular by
      the WHO, leaning on the careful inspection of scientific publications from
      numerous countries, conclude that current data do not allow to assert the
      existence of sanitary effects; however our knowledge of the biologic effects of
      electromagnetic fields still contains certain gaps which should be filled.
      Indeed, the numerous epidemiological studies relative to the occurrence of cancer
      by exposure to electromagnetic fields are conflicting. In every case the increase
      of the risk, when described, is always weak. The measure of the Relative Risk
      (RR) which establishes the relation is approximately 2-3. At present, some data
      concerning the risk of childhood leukemia in the event of exposure of ELF
      generated in the home indicate that this risk can exist when children are
      chronically exposed to more than 0.4 micro T (the relative risk is in the order
      of 2). In the field of radio frequencies, the increasing use of cell phones (38
      million users in France) and their antennae - basis are another subject of
      concern for the effects on health they are susceptible to produce. Large-scale
      studies, implying numerous countries, carried on at present within the framework
      of the WHO should bring elements of answer to the unresolved questions.

PMID- 15243341
TI  - [Mastocytosis: advances in molecular diagnosis and therapeutics].
AB  - Systemic mastocytosis is a rare myeloproliferative-like disease, characterized by
      an abnormal proliferation of mast cells in various organs. Two types of clinical
      manifestations can be distinguished: those related to release of mast cell
      mediators release and those related to tumor proliferation involving different
      organs, these later defining systemic mastocytosis. Until recently, treatment was
      mainly symptomatic, without anti tumor effect. These last years, advances have
      been made in the understanding of the disease with the discovery of the presence,
      in a number of patients, of mutations of the c-kit oncogene, coding for the
      receptor of the major growth factor for mast cells. These mutations induce
      autophosphorylation of the c-kit receptor in the absence of its ligand, the Stem
      Cell Factor. Based on experiences acquired in the treatment of myeloproliferative
      disorders, evaluation of new therapeutics, such as cladribine or interferon
      alpha, is in progress. Finally, it would be possible to design, in the very next
      future, new tyrosine kinase inhibitors targeting specifically the mutant forms of
      c-Kit found in patients suffering from systemic mastocytosis.

PMID- 15243342
TI  - [Legionella and legionellosis: of water, bacteria and men].
AB  - Legionella species are natural dwellers of stagnant waters. Inhalation of
      contaminated aerosols may result in pneumonia, with a noteworthy mortality rate
      (20%). However, such infections are infrequent, when compared to the rate of
      human exposition to Legionella. Legionellosis apparently occurs in patients in
      which respiratory tract macrophages allow bacterial replication, especially that
      of Legionella pneumophila serogroup 1. Following a silent incubation period,
      large amounts of bacteria are released, resulting in a strong inflammatory
      response responsible for the severity of symptoms. The outcome depends on quick
      establishment of antibiotic therapy and early diagnosis is therefore necessary.
      Nowadays, the risk of acquiring legionellosis raises passionate discussions, in
      which the presence of Legionella in man-made water systems is often assimilated
      with the disease itself. Significant efforts are being made to detect and monitor
      the amount of Legionella in potentially contaminant environments. However, the
      prevention of legionellosis also requires that research efforts for a better
      understanding of the virulence mechanisms of infective strains are carried out.

PMID- 15243343
TI  - [Stem-cell engraftment as delayed therapy to repair organophosphate-induced brain
      damage].
AB  - Amongst organophosphate compounds, both pesticides and warfare neurotoxics are
      probably the most representative. These compounds are irreversible
      acetylcholinesterase inhibitors. Usual clinical signs observed after acute
      poisoning are mainly respiratory distress, convulsions and seizures. Following
      acute poisoning, an emergency treatment must be provided as soon as possible
      (maximum delay of 1 hour post-poisoning), to prevent irreversible brain damage
      and patient death. At the present time, there is no efficient delayed treatment
      which could be provided if this 1 hour latency is overpassed. However,
      neurogenesis by stem cell engraftment, eventually complemented by gene therapy
      strategy, could be a potential therapeutic approach to repair organophosphate
      induced brain damage. Main stem cell engraftement strategies successfully used
      for brain damage of various origins are reviewed in this Article.

PMID- 15243344
TI  - [Medication and pregnancy counseling, an incomfortable role for the retail
      pharmacists].
AB  - Tragedies subsequent to use of medication at the beginning of pregnancy have
      given rise to extreme distrust, placing the retail pharmacist in an uncomfortable
      situation. A survey of pharmacists in France has revealed that pregnant women ask
      for more information than any other patients, particularly when it comes to
      continuing medication started before pregnancy. In such cases, 57% of the polled
      pharmacists recommended discontinuation of the medication. Ninety percent thought
      they were sufficiently informed and massively recommended a prudent attitude.
      Their wish was to have an independent high-performance information tool
      available. There is such a tool: the Teratogenic Agent Information Center, rarely
      used by pharmacists. With the support of such a structure, 80% would be eager to
      take on more responsibilities in counseling patients and preventing teratogenic
      risks, in relation with other healthcare workers, thus guaranteeing high-quality
      medication counseling.

PMID- 15243345
TI  - [Informational causality of the effect of drug signal].
AB  - Application of the inflammation theory in pharmacology leads to discuss the
      causality of the drug signal effect and compare the properties of informational
      causality with substantial and energetic causalities. This provides particular
      insight concerning drug efficacy.

PMID- 15243346
TI  - [Initiation to military medical corps activity modalities: a teaching unit
      providing a new approach to recruiting reserve pharmacists].
AB  - During the last ten Years, major reforms have been implemented in the French
      armies due to discontinuation of mandatory enlistment. For the medical corps,
      recruitment and training for reservists has ceased since the national school for
      reserve officers in Libourne was closed. During this same time, the number of
      foreign engagements of the French armies has revealed the need for available
      young reserve officers in the medical corps. Reserve training of students in
      medicine, pharmacy, odontology, or nursing has been considered and different
      possibilities considered. One option is to develop a teaching unit during the
      third Year of the curriculum allowing volunteer students to become junior
      officers. For pharmacy students, specific training on drug supply, nuclear,
      biological and chemical weapons and terrorism as well as clinical chemistry,
      toxicology, and hygiene are also organized.

PMID- 15243347
TI  - [Tribute to Paul Janssen (1926-2003): two discoveries per year"].
AB  - Paul Janssen (1926-2003) performed during fifty Years an intense pharmaceutical
      research activity. From 1953 to 2003, he discovered numerous new drugs in various
      fields of pharmacology. He widened the neuroleptic spectrum with haloperidol and
      risperidone, the opioid one with dextromoramide, fentanyl and its short-life
      derivates, constipating agents like loperamide, hypnotics, anaesthetics. In the
      field of anti-infectious agents, he discovered azole antifungals, parasiticides
      among which levamisole and mebendazole. Other therapeutic classes have been
      enriched by JANSSEN's works: vasodilatating agents, antihypertensive and anti
      allergic drugs, etc. More recently, his research was oriented towards virology
      namely anti-HIV drugs. When Paul JANSSEN's life ended, his scientific production
      seemed to be one of the most eminent in the XXth century.

PMID- 15243348
TI  - [Diabetes mellitus, oxidative stress and advanced glycation endproducts].
AB  - Chronic hyperglycemia in diabetes mellitus is an oxidative stress created by an
      imbalance of prooxidants over antioxidant defenses. The pathogenesis would
      involve several mechanisms including glucose autoxidation, protein glycation, the
      polyol pathway, and overproduction of superoxide radicals in mitochondria and via
      NAD(P)H oxidase. Glycemic equilibrium plays a very important role in the
      prooxidant/antioxidant balance. Macromolecules such as found in the extracellular
      matrix, lipoproteins, and deoxyribonucleic acid also constitute targets for free
      radicals in diabetes mellitus. This oxidative tress is involved in the
      pathophysiology of diabetes complications. The chronic hyperglycemic status also
      favors glycation reactions (irreversible glucose binding on protein amino
      groups), thereby leading to advanced glycation endproducts. Via their recognition
      by cell receptors, advanced glycation endproducts also participate in the
      development of oxidative stress and the inflammatory status. Involvement of
      oxidative stress and advanced glycation endproducts in diabetes complications is
      the basis of the development of adjunct therapies with antioxidant and/or
      anti)advanced glycation endproducts molecules.

PMID- 15243349
TI  - [Synthetic drugs consumed at "rave parties"].
AB  - Significant health risks result from the rising consumption of psychoactive drugs
      employed for festive objectives. Once alerted by this new danger, the French
      interministerial mission for the fight against illicit drugs and drug abuse
      (MILDT) set up a system of chemical and social studies in collaboration with the
      European Office of Drugs and Drug Abuse. The goal of the project is to discover
      the chemical structure of currently used drugs, and to study and predict their
      pharmaco-toxicaological effects. Over the last five Years, the laboratory of the
      Fernand Widal Hospital has analyzed more than 2,000 samples: 181 different
      molecules have been identified, ranging from inoffensive agents to very active
      drugs, including some misused licit drugs. Many of the compounds identified are
      amphetamine derivatives. The most widespread drug was ecstasy. Consumers and
      dealers seek substances with more potent psycho-stimulating effects which are not
      on the narcotics list and less expensive, producing effects as close to ecstasy
      as possible. In this extremely permissive context, other non-amphetaminic
      products are in circulation, including anesthesics such as ketamine and CHB,
      leading users to unconscious assent. The medical risks increase even more when
      several psychoactive substances are consumed in combination.

PMID- 15243350
TI  - [Busulfan and cycosporin in bone graft children].
AB  - Most drugs exhibit both inter- and intra-individual pharmacokinetic and
      pharmacodynamic variability. This variability explains the different responses
      observed in patients exposed to standard doses and must be taken into
      consideration when the therapeutic window is narrow. Population pharmacokinetics
      provides mean (or median) values of pharmacokinetic parameters as well as the
      distribution pattern and the statistical relationship with covariables in a group
      of individuals presenting common characteristics. Among the different methods
      developed for population pharmacokinetics, the data pool method, as well as the
      two-step and one-step methods (NONMEM and NPEM) are attractive. Population models
      can then be developed using bayesian logistics to obtain an estimation of the
      pharmacokinetic parameters of a given patient and predict the most adapted dose
      in light of the therapeutic target (residual serum concentration, mean
      concentration.). Busulfan is an alkylizing agent used instead of radiotherapy for
      pre-graft preparation before bone marrow grafts in children. This compound
      requires dose monitoring because of its narrow therapeutic window: under-dosing
      raises the risk of graft rejection; inversely over-dosing can cause potentially
      fatal complications such as occlusive venous disease. Interindividual variability
      is characteristic of busulfan kinetics. Several factors can explain part of this
      variability: age, underlying disease, changes in liver function, drug
      bioavailability, chronobiology. The short treatments used (most protocols have 16
      doses given in four days) require rapid monitoring to propose effective
      adjustments. In this context, use of bayesian logistics to estimate the patient's
      pharmokinetic parameters is very useful for correct dosing. This type of
      monitoring could also be used for other compounds such as cyclosporine, with a
      narrow therapeutic window.

PMID- 15243351
TI  - [Pharmacokinetics and dose adaptation of ofloxacine, pefloxacine and
      ciprofloxacine during haemodialysis and continuous ambulatory peritoneal
      dialysis].
AB  - Fluoroquinolones present various pharmacokinetic properties. That's the way we
      carried out a bibliographic summary about the pharmacokinetics of pefloxacin,
      ofloxacin and ciprofloxacin in patients hit by chronic renal failure, under
      haemodialysis or under continuous ambulatory peritoneal dialysis. Then, we will
      describe how to adapt drug dose according to the degree of renal insufficiency
      and the used molecule.

PMID- 15243352
TI  - [Melt granulation with glyceryl palmitostearate to obtain taste-masked
      acetaminophen].
AB  - A melt granulation process designed to obtain a taste-masked acetaminophen using
      glyceryl palmitostearte (Precirol Ato 5) is described. Melting this lipid
      material in a high-smear mixer gives granules which can be directly compressed
      after blending with the required excipients. The phase diagram shows the absence
      of interaction between the phases of the two components and no effect on
      acetaminophen polymorphism. A water dispersible tablet formulation is proposed
      for oral administration of cristallized acetominophen (500 mg) devoid of
      bitterness of which 90% dissolves within 15 minutes.

PMID- 15243353
TI  - [Plasma assay of methadone enantiomers with high performance liquid
      chromatography].
AB  - 6-Dimethylamino-4,4-diphenylheptane-3-one (methadone) is a synthetic opioid.
      Presence of an assymetrical carbon in its structure explains existence of two
      enantiomers. Levogyral enantiomer or R-methadone exhibits an 25 fold superior
      analgesic activity to the dextrogyral enantiomer S-methadone. In order to run
      separately a plasma assay of these two enantiomers, a chromatographic chiral
      separation method coupled with an ultraviolet detection has been performed. It
      allows selective assay of each enantiomer. This method, although an analytical
      interference with d-propoxyphene, is sensitive, reproductible, specific and shows
      a convenient resolution for the analysis of both the stereospecific and racemic
      forms. This method can be applied for pharmacokinetic study of the drug in
      patients treated by methadone.

PMID- 15243354
TI  - [Revision of the European pharmaceutical legislation].
AB  - In accordance with the Regulation N 2309/93/EC, the Commission shall produce a
      synopsis of European registration operating procedures no later than 2001. On
      July 18, 2001, after a wide open consultation, the College of Commissioners
      adopted a Proposed Revision elaborated by the "DG Enterprises". This Proposed
      Revision was guided by the desire to facilitate access of citizens of the
      European Union to innovating and safe medications, to limit fragmentation of the
      interior market, prejudicial to the community pharmaceutical industry, and to
      prepare widening of the community. This synopsis focused essentially on
      registration procedures and pharmacovigilance, on patient information, on reform
      of the European agency for administrative protection of recorded data. The
      Proposed Revision is following the codecision procedure and should come into
      force, in a more or less amended form, at the end of 2004 at the latest.

PMID- 15243355
TI  - [Drug registration file prerequisites for European procedures].
AB  - The pharmacokinetic content of the drug registration file is now well
      standardized. The objectives of the pharmacokinetic documentation is to provide
      evidence supporting the dosing regimen in patients, to take into account the
      pathophysiological states of the populations at risk and to anticipate drug-drug
      interactions. Recommendations on study design and evaluation of parameters of
      interest are listed in various documents Issued by the Committee for Proprietary
      Medicinal Products and the International conferences on Harmonization, i.e. the
      Concept Papers, the Points to Consider and Notes for Guidance. The
      pharmacokinetic data of the registration file are used to document many sections
      of the Summary of the Product Characteristics.

PMID- 15243356
TI  - [An argument for the harmonization of technics and management of vascular
      pathologies].

PMID- 15243357
TI  - [Case report: imaging of the renal arteries: when, how and why?].

PMID- 15243358
TI  - [Imaging of the extracranial carotid arteries: when, how and why?].
AB  - The indications for treating carotid artery stenosis are related to the
      symptomatic nature of the lesion and the degree of stenosis. Duplex sonography is
      adequate for screening. While some groups believe that Duplex US alone or in
      combination with transcranial Doppler imaging may be sufficient for presurgical
      evaluation, it often is recommended to complete the evaluation with either MRA or
      CTA. Both techniques are advantageous since they allow evaluation of the cervical
      and intracranial arteries as well as cerebral parenchyma hence providing valuable
      information prior to definitive management. Catheter angiography remains
      indicated in patients with multi-vessel disease and ischemic cardiomyopathy, when
      results at non-invasive evaluation are discordant or in an emergency setting.
      Duplex US is used for routine follow-up of non-surgical lesions and after
      endarterectomy. Transcranial Doppler as well as advances in MRA and CTA
      techniques will be reviewed. Even though the treatment of atherosclerotic carotid
      artery stenoses remains primarily surgical, specific considerations related to
      angioplasty will be reviewed. Finally, diseases of the intracranial carotid
      artery and non-atherosclerotic diseases (dissection...) will also be discussed.

PMID- 15243360
TI  - [Case report: imaging of the lower limb arteries: when, how and why?].

PMID- 15243359
TI  - [Imaging of the lower limb arteries: when, how and why?].
AB  - Noninvasive screening of lower limb arterial disease has long been performed
      using color Doppler ultrasonography, whereas surgical or endovascular treatment
      planning relied on conventional angiography. With continued improvements of
      noninvasive imaging modalities, it is now possible to image the entire lower limb
      vasculature without arterial catheterization. Multidetector row helical CT
      angiography has the advantage of visualizing the arterial lumen and arterial wall
      calcifications, and nephrotoxicity is reduced by decreasing amounts of contrast
      medium. Three-dimensional MR angiography is a safe procedure, with high contrast
      sensitivity, and has recently benefited from step table technology that allows a
      single injection of contrast medium. The literature shows that both helical CT
      and MR angiography have high levels of accuracy, but outcome studies of their
      respective role in the setting of acute and chronic lower limb ischemia are
      lacking. These noninvasive techniques should play a major role in two main
      situations: first, in critical ischemia where therapeutic planning should ideally
      be achieved non invasively; second, in the follow-up of treated patients
      presenting with recurrent ischemia.

PMID- 15243361
TI  - [Imaging of the thoracic aorta in adults: when, how and why?].
AB  - CT, MRI and transesophageal echocardiography have become the standard of
      reference for evaluation of the thoracic aorta. Angiography is mainly performed
      as a presurgical procedure. Congenital pathologies observed during adulthood
      include coarctation, patent ductus arteriosus, and aberrant retroesophageal
      subclavian arteries. Imaging plays a major role for diagnosis and management of
      patients with acute aortic syndromes: intramural hematoma, dissection,
      penetrating ulcer and nondissecting aneurysms. Cross sectional imaging of the
      thoracic aortic wall allows evaluation of inflammatory diseases of the aorta or
      aortitis.

PMID- 15243362
TI  - [Imaging of abdominal aortic aneurysms: when, how and why?].
AB  - Usually atherosclerotic in origin, aneurysms of the abdominal aorta (AAA) tend to
      involve the infrarenal aorta. Their biphasic exponential growth pattern,
      initially slow then accelerated, results in a risk of rupture. Surgical
      management is recommended for aneurysm diameters of 45-50mm or for growth rates
      more than 5mm in 6 Months. Imaging is useful for detection and follow-up of
      nonsurgical aneurysms, presurgical evaluation of aneurysms, and postsurgical
      follow-up. Frequently asymptomatic, AAA frequently is an incidental finding at
      the time of abdominal US. The size of the aneurysm sac, the presence of a neck
      and the size of the iliac arteries are assessed at the time of initial US
      detection. US is sufficient for follow-up of small aneurysms. Cross sectional
      imaging evaluation is necessary when surgery is contemplated. Readily available,
      multidetector row CT scanners with advanced image post-processing capabilities
      provide all the necessary information prior to surgical or endovascular
      management: evaluation of the aneurysm sac and neck, iliac and visceral arteries,
      and adjacent organs. Angiography with graduated catheters remains sometimes
      indicated. MR angiography provides results similar to CT but is less readily
      available and is usually reserved for patients with contraindication to iodinated
      contrast material. While follow-up imaging after surgical management is seldom
      performed, it is mandatory after endovascular management and includes KUB,
      Doppler US and CT or MR angiography.

PMID- 15243363
TI  - [Case report: imaging of abdominal aortic aneurysms: when, how and why?].

PMID- 15243364
TI  - [Imaging of the lower limb veins: when and how?].
AB  - Evaluation for possible lower limb deep venous thrombosis (DVT) is a very
      frequently requested examination. In France, imaging diagnosis is essentially
      based on complete Doppler sonographic evaluation of both lower limbs. In patients
      with no co-morbid condition, the D-dimer assay is useful to exclude the
      possibility of DVT. A positive diagnosis of DVT is based on the lack of venous
      compressibility and abnormal Doppler signal. The diagnostic accuracy relies on
      adequate knowledge of vascular anatomy and sufficient training, especially at the
      calf level. For experienced sonographers, the accuracy is similar at the thigh
      and calf level. In patients with suspected pulmonary embolus, evaluation of the
      lower extremity veins is mandatory and frequently performed with CT immediately
      following CT pulmonary angiography. However, this examination has not been
      validated yet.

PMID- 15243365
TI  - [Case report: imaging of the lower limb veins: when and how?].

PMID- 15243366
TI  - [Imaging of the pulmonary arteries: when, how and when?].
AB  - For several years, catheter angiography was the standard imaging technique used
      for evaluating the pulmonary arteries. Technical advances with computed
      tomography have had a significant impact on chest imaging, especially the
      increasing availability of multidetector row CT units. CT pulmonary angiography
      (CTPA) is now the first line imaging technique to evaluate pulmonary arterial
      diseases, including pulmonary embolus. Pulmonary angiography is now essentially
      limited to the endovascular management of pulmonary arteriovenous malformations,
      pulmonary arteriovenous fistulas or pulmonary arterial aneurysms. Gadolinium
      enhanced MR angiography of the pulmonary arteries may be helpful in patients with
      contraindications to the use of iodinated contrast material.

PMID- 15243367
TI  - [Case report: imaging of the pulmonary arteries: when, how and when?].

PMID- 15243368
TI  - [Radiologic spectrum of specific vascular diseases].
AB  - The diagnosis of vascularitis should be proposed when a concentric and regular
      thickening of the wall of the aorta or one of its branches is observed or when
      there is late enhancement of the arterial wall, on sites which are usually free
      from atheromatous lesions and in a young patient. The radiologist must be aware
      of the associated clinical signs: oral and genital ulcerative lesions in the
      Behcet syndrome; finger necrosis in a young male smoker in Buerger disease; hip
      and shoulder arthropathy and headache in a 70 Year old female and Horton disease;
      pulseless upper limbs and inflammatory syndrome in a young adult for the Takayasu
      arteritis. The diagnosis of popliteal entrapment or adventitial cyst should be
      proposed in young patients without atheromatous lesions.

PMID- 15243369
TI  - [Case report: radiologic spectrum of specific vascular diseases].

PMID- 15243370
TI  - [Diffusion-weighted MR imaging of the abdomen: a new clinical tool?].

PMID- 15243371
TI  - [MR imaging and arrhythmogenic right ventricular dysplasia (ARVD)].
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy of unknown
      etiology responsible for 20% of cases of sudden death in young adults secondary
      to arrhythmia. It is characterized histologically by fatty or fibro-fatty
      infiltration of the right ventricular myocardium. Diagnostic criteria have been
      proposed for diagnosing ARVD. Imaging, especially MRI, plays an important role.
      MR imaging must be performed using cardiac gating, and should include both cine
      MR sequences for evaluation of segmental and global right ventricular function or
      any morphological change of the right ventricular shape, and anatomic sequences
      to detect fatty or fibro-fatty infiltration of the right ventricular myocardium.

PMID- 15243372
TI  - [Value of N-acetylcysteine to prevent nephrotoxicity from iodinated contrast
      agents].
AB  - Renal toxicity of contrast agents remains an up-to-date challenge. N'Acetyl
      cystein is an antioxyde agent which efficacy has been proved in various models of
      experimental renal ischemia and therefore proposed in the prevention of renal
      failure due to intravenous iodine contrast media. The Author of this review
      reports and comments these studies in order to better define indications of
      N'Acetyl cystein in this clinical context.

PMID- 15243374
TI  - [Pedunculated uterine leiomyoma].

PMID- 15243373
TI  - [Cerebellar cortical dysplasia: MRI aspects and significance].
AB  - Because it is now possible to obtain high-resolution multiplanar MR imaging of
      the cerebellum and because of the developing interest on the role of the
      cerebellum on higher brain functions, we have decided to study the process of
      cerebellar fissuration. All brain MRI examinations performed in children for
      varied neurological and neurosurgical indications, especially children with non
      specific mental retardation and patients with cerebral malformation detected at
      initial imaging work-up, were reviewed. Fissuration and lobulation anomalies
      (abnormal orientation of fissures, pseudopolymicrogyria, cortical thickening,
      subcortical cysts and heterotopia) were identified that we called cerebellar
      cortical dysplasia (CCD). In order to better understand the origin of this
      malformation, current data on cerebellar embryogenesis and histogenesis will be
      reviewed, and the pathological and radiological features will be illustrated.
      Milder forms of CCD represent a distinct group of anomalies that should be
      distinguished from other types of cerebellar dysplasia (agenesis, hypoplasia or
      complex dysplasia with involvement of the cerebellar vermis
      (rhombencephalosynapsis)) or combined cerebellar and cerebral dysplasia (muscular
      dystrophies and lissencephaly). Recognition of cerebellar cortical dysplasia
      could be a first step towards a broader understanding of its pathogenesis and
      significance.

PMID- 15243375
TI  - [Low dose helical CT pelvimetry: evaluation of radiation dose and image
      processing].
AB  - PURPOSE: to estimate from phantom measurements the radiation dose and the
      accuracy of helical ct pelvimetry. MATERIALS AND METHODS: Eight helical CT
      acquisitions using different tube current (100, 50, 25 or 10mAs) and pitch factor
      (1.125 or 1.375) settings but identical collimation (2mm) and kilovoltage (120
      kVp) were evaluated using a four-channel MDCT scanner and compared with
      conventional CT pelvimetry including a single scout and two transverse images. A
      plexiglas phantom combined with an ionization chamber was used to calculate the
      CTDIw and DLP for each acquisition. Then, an ex vivo phantom of bony pelvis was
      used to evaluate the accuracy of helical acquisitions for the measurement of
      pelvic diameters (i.e. the antero-posterior inlet, the transverse inlet and the
      interspinous distance). Reconstructions of helical acquisitions were performed
      using 2D MPR, 3D MIP and 3D SSD algorithms. RESULTS: CTDIw and DLP of
      conventional pelvimetry were 26 mGy and 42 mGy.cm respectively. The radiation
      dose of helical acquisitions decreased linearly with tube current (CTDIw: from 13
      to 1.3 mGy, DLP: from 218.3 to 18.7 mGy.cm). Compared to conventional CT, the
      dose was nearly similar at 25 mAs and reduced at 10 mAs. Helical acquisitions
      provided accurate measurements of pelvic diameters with a pitch of 1.125 and a 2D
      MPR algorithm to evaluate the AP inlet and a 3D MIP algorithm to evaluate the
      transverse inlet and the interspinous distance. Variations of tube current did
      not influence the accuracy of pelvic diameter measurement. CONCLUSION: Our
      results suggest that accurate low-dose helical CT pelvimetry using 10-25 mAs and
      a pitch factor of 1.125 combined with 2D MPR and 3D MIP reconstructions is
      possible.

PMID- 15243376
TI  - [Value of combined conventional and contrast enhanced sonography in the
      evaluation of hepatic disorders].
AB  - PURPOSE: To assess the value of combined conventional and contrast-material
      enhanced sonography for the characterization of focal liver lesions. MATERIALS
      AND METHODS: Simultaneous imaging with grey scale and contrast enhanced US was
      performed in 90 patients following Levovist injection (Schering, Berlin, Germany)
      using the "Agent Detection Imaging" method (ADI, Siemens-Acuson, Mountain View,
      USA). US scanning was performed at least 4 minutes after contrast injection with
      review of both grayscale and contrast enhanced modes. Results for detection and
      characterization of lesions were compared to the selected gold standard imaging
      modality (CT or MRI). RESULTS: Final diagnoses included: 20 normal examinations,
      41 patients with metastases, 6 patients with hepatocellular carcinoma, 13
      patients with hemangioma, 6 patients with other benign lesions, 4 patients with
      cysts and 6 patients with two types of lesions. Delayed phase contrast enhanced
      US allowed diagnosis of all lesions except for one metastasis and all
      hepatocellular carcinomas. While the diagnosis of hepatoma could not be
      confirmed, the features suggested a malignant etiology. For 7 patients with
      metastases, more lesions were detected at ADI (4.9 lesions) than at conventional
      US (1.1 lesion). For 3 patients, CT showed more lesions than ADI US (3.3 versus
      1.6 lesions). The accuracy of ADI US for differentiating between benign and
      malignant lesions was 98.7% compared to 49.6% for conventional US (p<0.001). The
      total number of lesions detected at ADI US was higher (p<0.01) than at
      conventional US and not significantly different from that obtained by the gold
      standard reference methods. Complete characterization was achieved in 92.2% of
      cases with ADI US compared to 59.2% with conventional US (p<0.001). CONCLUSION:
      Contrast-material enhanced US combined with conventional US markedly improves the
      diagnostic accuracy of US in terms of lesion detection and characterization.

PMID- 15243377
TI  - [Sonographic evaluation of periportal fibrosis in children living in a
      Schistosoma mansoni endemic region].
AB  - PURPOSE: To assess with ultrasound periportal fibrosis due to chronic Schistosoma
      mansoni infection in children living in an endemic region. Materials and methods.
      A total of 441 children underwent two stool examinations and abdominal
      sonography. Liver echotexture was assessed by two observers and compared to pre
      defined image patterns and a fibrosis score was assigned ranging from 0 to 8.
      Ultrasound features were correlated to age, sex, and parasitologic findings.
      RESULTS: Prevalence of Schistosoma mansoni infestation was 63%. Two cases of
      advanced fibrosis (E pattern or fibrosis score of 6) were observed. Fibrosis
      correlated with age. No correlation existed between fibrosis and intensity of egg
      output. A correlation between the two examinors was noted in 84% of examinations
      with a kappa coefficient of 0.7. CONCLUSION: Although severe periportal fibrosis
      is a rare finding in this endemic region, follow-up sonography must be performed
      because it is the only non invasive and reliable tool for detection of periportal
      fibrosis.

PMID- 15243378
TI  - [Urogenital bilharziasis: imaging diagnosis].
AB  - Urogenital bilharziasis is a well-known disease that seldom is encountered in
      western countries. Therefore, bilharziasis usually only is considered after
      tuberculosis, the main differential diagnosis, has been excluded. Using this
      case, we will discuss the value of different imaging techniques (especially that
      of CT combined with transrectal US) for diagnosing bilharziasis and review
      specific criteria to more easily distinguish both pathologies.

PMID- 15243379
TI  - [Atypical presentation of an intestinal duplication in a three month old child].
AB  - Intestinal duplication is an uncommon congenital anomaly that often is diagnosed
      during childhood. Ultrasound diagnosis is based on the presence of a
      characteristic double-walled cystic mass. We report a case of duplication in a
      three Month old child presenting with small bowel obstruction. This case is
      unusual due to the presence of calcifications that are uncommon in intestinal
      duplication.

PMID- 15243380
TI  - [Tension pneumothorax from a perforated gastric ulcer].
AB  - Fistulous communications between the abdomen and pleural space are rare. The
      Authors report a case of hydropneumothorax following transdiaphragmatic
      perforation of an anterior wall gastric ulcer.

PMID- 15243381
TI  - [Paratesticular rhabdomyosarcoma. A case report].
AB  - The rhabdomyosarcomas are rare tumors of mesenchymal tIssue. Whose most frequent
      localisations are genito-urinary, and occur in the child and young adult. It's an
      intrascrotal tumour, localised in the tunica vaginalis, epididymis or spermatic
      cord. The Authors report a case of paratesticular rhabdomyosarcoma in a 15 Year
      old child, who presented a right painless scrotal mass since two Months. The
      research of the tumoral markers is negative. Scrotal ultrasound shows a tissular
      mass in spermatic cord. Abdominal ultrasound and CT show retroperitoneal lymph
      node mass. Chest X-ray is normal. The intervention consists of a right
      castration. The histological examination of the spiceman confirms the diagnosis
      of the paratesticular rhabdomyosarcoma of the spermatic cord. The patient is
      treated by chemotherapy without improvement. Through this observation, the
      Authors underline the interest of the imagery and the aspects of the
      paratesticular tumours in ultrasound and CT.

PMID- 15243382
TI  - [Transradial approach for diagnostic angiography].
AB  - Seventy five arteriographies were performed via the transradial route using 5F
      130cm - long catheter. Prior to puncture the radial artery was evaluated with
      Allen test. Satisfying quality examinations were obtained for the thoracic aorta,
      selective carotid arteries examinations, infra renal aorta, pelvic and legs
      arteries. The major advantages obtained for the technique were the very low rate
      complication and technical failure. Transradial route for arteriography is a
      reasonable alternative approach to transfemoral or brachial arteriography for out
      patient management (peripheral angiography) in case in which transfemoral route
      is not feasible but also with patients with important haemorragic-risks.

PMID- 15243383
TI  - [What is your diagnosis? Inferior mesenteric vein pylephlebitis due to sigmoid
      diverticulitis ].

PMID- 15243384
TI  - [Treatment of hepatitis C and drug addiction: is the development of "clinically
      significant" fibrosis a good decision-making criterion?].

PMID- 15243385
TI  - Management of hepatitis C in active drugs users: experience of an addiction care
      hepatology unit.
AB  - OBJECTIVE: Recent guidelines on the management of patients chronic hepatitis C
      virus (HCV) infection recommend the same anti-HCV therapy for active intravenous
      drug users and other patients, however some physicians are reluctant to treat
      active drug users. The aim of this study was to compare hepatitis C management
      practices and clinical outcome after treatment between active intravenous drug
      users and other patients. METHODS: Four hundred and thirty-five naive HCV
      seropositive patients were recruited from 1990 to 2000 and followed up for a mean
      period of 2.5 years (SD 1 Year). At the beginning of the study, 116 of the
      patients were active intravenous drug users. Social, clinical, biological and
      histological data were collected. The different steps of HCV management and
      responses to treatment were compared between active intravenous drug users and
      other patients. RESULTS: There was no statistically significant difference in HCV
      management practices and compliance between active intravenous drug users and
      other patients: search for viral RNA (85% versus 67%), liver biopsy performed
      when indicated (82% versus 87%), initiation of anti-HCV treatment (33.6% versus
      43.2%), loss to follow up during treatment (24% vs 16%). The rate of sustained
      viral response was not significantly different between active intravenous drug
      users and other patients (28% versus 21%). At multivariate analysis, factors
      independently associated with sustained viral response were female gender (OR=5.6
      [1.02-41.2]), genotype 3 (OR=29.7 [1.4-61.7]), low viral load (OR=33.3 [2.25
      100]), low fibrosis score (OR=1.4 [1.0-2.0]), elevated transaminase level
      (OR=12.7 [0.9-97.2]), and bitherapy protocol (OR=10 [1.18-85.3]). CONCLUSION:
      This study illustrates that active intravenous drug use does not affect either
      patient compliance with proposed management or viral response to treatment, but
      pluridisciplinary care should focus both on drug addiction and HCV infection.

PMID- 15243386
TI  - [Hepatotoxicity associated with herbal remedies: clinical, biological,
      histological data and the mechanisms involved in some typical examples].

PMID- 15243387
TI  - [Are the definitions of functional digestive disorders based on the Rome criteria
      useful in clinical practice?].

PMID- 15243388
TI  - Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic
      criteria.
AB  - OBJECTIVES: The main objectives of this study were to assess whether the use of
      different definitions of irritable bowel syndrome (IBS) could influence
      measurements of its prevalence and characterize the patient population fulfilling
      these different diagnostic criteria. METHOD: A telephone survey was carried out
      by contacting 8,221 subjects aged >or=18 Years representative of the French
      population. A "screening" questionnaire based on three algorithms of IBS
      classification (Manning, with or without a notion of a minimal duration of
      symptoms, Rome I and Rome II) was used by specialised inquirers. RESULTS: Twenty
      three percent of the subjects interviewed stated that they had suffered from
      abdominal pain during the previous 12 Months. The prevalence of IBS considerably
      varied, depending on the diagnostic criteria used: 12% based on Manning criteria
      without reference to the duration of symptoms; 2.5% if the notion of duration of
      symptoms was added to the Manning criteria, and 2.1% and 1.1% based on the Rome I
      and Rome II criteria, respectively (the latter including the same notion of
      duration). In total, 212 subjects (2.6%) met at least one of the criteria
      including a minimal duration of symptoms, with a predominance for women (sex
      ratio close to 2). CONCLUSION: The prevalence of IBS is strongly dependent on the
      classification algorithm employed. The requirement of a minimum duration of
      symptoms eliminates IBS in a large number of subjects complaining of abdominal
      disorders. Once these methodological variations were taken into account, the
      prevalence of IBS in France was found to be comparable to that published in
      international literature.

PMID- 15243389
TI  - Validation of the French version of the Fecal Incontinence Quality-of-Life (FIQL)
      scale.
AB  - INTRODUCTION: The aim of this multicenter study was to validate the French
      version of the fecal incontinence quality-of-life scale (FIQL scale) developed in
      the Unites States of America. PATIENTS AND METHODS: The FIQL scale has 29 items
      in four scales: lifestyle, coping/behavior, depression/self-perception and
      embarrassment. Each item is scored from 1 to 4, with poorest quality-of-life
      scored 1. An average is calculated for each scale. After linguistic validation of
      the questionnaire, the French version of the FIQL scale was tested twice, at day
      0 and day 7, by 100 patients with fecal incontinence (FI). Construction validity,
      internal reliability, clinical validity and reproducibility were analysed.
      RESULTS: Analysis of convergent validity of the French version of the FIQL scale
      showed very good correlation between items and the corresponding scale for
      lifestyle (0.50-0.79) and depression/self-perception (0.44-0.74), good
      correlation for coping/behavior (0.31-0.70) and weak correlation for
      embarrassment (0.30-0.40). Valid discrimination was observed for 24 of the 29
      items. Internal reliability was good for each scale (alpha Cronbach between 0.78
      and 0.92). Scores determined with the FIQL scale were significantly correlated
      with Wexner FI scores, demonstrating the clinical validity of the instrument.
      Reproducibility, evaluated in patients whose FI was unchanged between day 0 and
      day 7, was good with intraclass correlation coefficients ranging from 0.80
      (embarrassment) to 0.93 (lifestyle). CONCLUSIONS: The linguistic and psychometric
      evaluation demonstrated the validity of the French version of the FIQL scale.
      This standardized instrument is now available for clinical use in France for
      quality-of-life assessment in patients with FI.

PMID- 15243390
TI  - Prospective evaluation of a new rapid urease test (Pronto Dry) for the diagnosis
      of Helicobacter pylori infection.
AB  - AIM: Rapid urease tests are commonly used to establish the diagnosis of
      Helicobacter pylori infection during upper endoscopy. The aim of this study was
      to evaluate the performance of a new rapid urease test (Pronto Dry) compared with
      histology as the gold standard. METHODS: Six gastric biopsies (three in the
      antrum and three in the fundus) were performed in 113 consecutive patients.
      Eighteen patients were later excluded from analysis because they did not fulfil
      the inclusion criteria. Four biopsies were examined by two experienced
      pathologists blinded to the rapid urease tests. Two biopsies (one from antrum and
      one from the fundus) were pooled for the rapid urease test which was read by the
      endoscopist 5 and 30 minutes later using the color scale (yellow, pink, orange,
      dark pink, fuchsia) provided by the manufacturer. RESULTS: According to the
      histology findings 32 of the 95 patients retained for analysis (33.7%) were
      positive for Helicobacter pylori. Considering that a positive test was indicated
      by the dark pink or fuchsia colors, sensitivity and specificity of Pronto Dry
      were 62.5% and 98.4% at 5 minutes and 84.4% and 98.4% at 30 minutes respectively.
      Twenty-one of the 28 positive rapid urease tests (75%) were already positive at 5
      minutes. CONCLUSION: Considering positive tests are indicated solely by the two
      darkest colors on the color scale, the performance of Pronto Dry is similar to
      that of other rapid urease tests. The rapid results provided by Pronto Dry in
      routine practice would seem to provide obvious advantages.

PMID- 15243391
TI  - [Desmoid tumors in familial adenomatous polyposis].

PMID- 15243392
TI  - [Folate metabolism and colorectal carcinogenesis].

PMID- 15243393
TI  - [Hepatic metastatic miliaria from a malignant melanoma: 2 case reports].
AB  - Malignant melanoma of uveal or cutaneous origins are diseases which may run a
      fulminant metastatic course immediately or after a prolonged disease-free period.
      The liver is the most common initial site of metastatic involvement.
      Nevertheless, hepatic metastatic miliaria spread is rare. In these cases,
      morphological studies are normal and only biological abnormalities including
      icteric cholestasis and hepatocellular insufficiency may suggest this diagnosis.
      We report two cases of hepatic metastatic miliaria from malignant melanoma
      diagnosed by percutaneous liver biopsy.

PMID- 15243394
TI  - [Paroxysmal nocturnal hemoglobinuria revealed by hepatic vein thrombosis (Budd
      Chiari syndrome) during Infliximab therapy].
AB  - We report the case of a 41-Year-old man presenting with hepatic vein thrombosis
      (Budd-Chiari syndrome) during Infliximab therapy for ankylosing spondylitis. The
      systematic work-up revealed paroxysmal nocturnal hemoglobinuria. One Year later
      the patient was receiving anticoagulation therapy and was in good condition. The
      role of Infliximab in the development of thrombosis in this patient with rare
      underlying thrombophilia is discussed.

PMID- 15243395
TI  - [Sarcomatoid carcinoma of the colon: report of a case and review of the
      literature].
AB  - Sarcomatoid carcinomas or carcinosarcoma are rare tumors composed of mixed
      carcinoma cells and mesenchymal cells. Thirteen cases with colorectal involvement
      have been published to date. We report a case of sarcomatoid carcinoma of the
      colon in a 67-Year-old woman hospitalized with a history of anemia and bloody
      stools. The patient underwent a left hemicolectomy. Immunohistochemistry revealed
      two cell components (undifferentiated carcinomatous and sarcomatous components).
      The patient died of her tumor 2 Months after the operation. Our review of the
      literature stresses the poor prognosis associated with colonic sarcomatoid
      carcinoma.

PMID- 15243396
TI  - [Membranous glomerulonephritis complicating hepatocellular carcinoma].
AB  - We report the case of a 65-Year-old man with advanced hepatocellular carcinoma
      related to alcoholic cirrhosis who was hospitalised for oliguric renal failure.
      Investigations showed a severe nephrotic syndrome related to paraneoplastic
      membranous glomerulonephritis. The patient's course was temporarily stabilized
      with loop diuretics and dialysis but the patient died of hemoperitoneum from a
      ruptured tumor.

PMID- 15243397
TI  - [Unexpected protective role of interferon-alpha against Mycobacterium
      tuberculosis during the course of hepatitis C antiviral therapy].

PMID- 15243398
TI  - [Pioglitazone-induced acute severe hepatitis].

PMID- 15243399
TI  - [Updating of the management of anorectal stromal tumors].

PMID- 15243400
TI  - [Use of endosonography in a patient with a rectal stromal tumor: a case study].

PMID- 15243401
TI  - [Metastatic obstruction of the small bowel complicating malignant pleural
      mesothelioma].

PMID- 15243402
TI  - [Collagenous colitis and temporal arteritis: a chance association?].

PMID- 15243404
TI  - PET/CT in diagnostic oncology.
AB  - In the last years positron emission tomography (PET) with 18F-fluorodeoxyglucose
      ([18F]FDG) has become an established technique for the staging and follow-up of a
      wide variety of neoplasms. As PET imaging is based on the physiological mediated
      distribution of the administered tracer, rather than on anatomic and structural
      characteristics of tissue, the addition of CT imaging to PET improves the
      interpretation of PET images. Recently, integrated PET/CT scanners have been
      developed that can produce directly functional PET and anatomical CT data 1
      session, without moving the patient and with minimal delay between the
      reconstruction and fusion of the 2 image data sets. In addition, CT images are
      also being used for attenuation correction in the reconstruction process of the
      PET emission data. A brief review of the most relevant technical characteristics
      of 3 PET/CT systems, which represent the state of the art of this technology, are
      described. Furthermore an overview of PET/CT acquisition protocols and clinical
      applications of PET/CT in oncology are described. Overall, advantages of PET/CT
      over PET that may influence the clinical routine, have been identified as a) the
      shorter image acquisition time with benefit on patients throughput and on patient
      compliance, b) the better accuracy in anatomically localizing focal areas of
      abnormal tracer uptake and defining tumor extent and c) the possibility to stage
      a disease in 1 single step.

PMID- 15243405
TI  - Position of nuclear medicine techniques in the diagnostic work-up of brain
      tumors.
AB  - Although any patient with a suspected brain tumor, either primary or metastatic,
      should be studied with anatomic imaging modalities such as angiography,
      computerized tomagraphy (CT) or magnetic resonance imaging (MRI), nuclear
      medicine techniques are available to further characterize some biological
      features of brain lesions and help in diagnosis and therapy planning. Bloob-brain
      barrier disruption can be easily assessed with single-photon emission tomography
      (SPET), whereas focal metabolic changes can be better demonstrated by positron
      emission tomography (PET) as specific radiopharmaceuticals are available to
      detect changes in glucose utilization and aminoacid uptake with this technique.
      Expression of specific tumoral antigens is the basis of imaging with
      radioimmunoscintigraphy, a promising technique that can be applied to brain tumor
      therapy. The major clinical applications of nuclear medicine in the study of
      brain tumors -- evaluation of the extension of a tumoral mass, differential
      diagnosis and evaluation of therapy and prognosis -- are discussed.

PMID- 15243406
TI  - Nuclear medicine in diagnosis, staging and follow-up of thyroid cancer.
AB  - Diagnostic strategy in thyroid cancer is conditioned by epidemiological,
      pathophysiological, cost-effective issues changing with age and countries.
      Nuclear medicine has a role mainly in differentiated carcinomas, i.e. in the
      large majority of thyroid cancers. In diagnosis of thyroid nodule (99m)Tc
      perthecnetate is indicated in patients with low TSH levels, multinodular goiter,
      solid nodules at US negative at FNA. Radiolabeled somatostatin analogs or
      Metaiodobenzylguanidine (MIBG) can be used in suspicion of medullary carcinoma.
      There is no role in staging. WBS with 131I has a role after surgical resection of
      the thyroid gland and it is no more suggested before ablative therapy, because of
      the possible stunning effect. In the follow-up thyroglobulin (Tg) test is
      mandatory both after therapy withdrawal or after rhTSH administration. Some
      authors already suggest to use this test alone, as 1st step, in patients with
      differentiated carcinoma at low risk of recurrence, but this approach is not yet
      generally accepted and it has not yet been validated in tumors at
      intermediate/high risk. WBS with 131I is ever indicated when autoantibodies can
      affect reliability of Tg values and in presence of high Tg levels to better
      define a radiometabolic therapy. In case of negative WBS, PET-FDG can be
      proposed. In WBS, 123I can be an alternative to 131I, but it is not yet generally
      accepted mainly because of its higher costs. The clinical use of rhTSH to
      increase accuracy both of Tg and WBS can be already accepted in patients at high
      risk following hypothyroidism, with a worst prognosis or a low pituitary
      response.

PMID- 15243407
TI  - Position of positron emission tomography and other imaging diagnostic modalities
      in esophageal cancer.
AB  - Positron emission tomography (PET) using the positron emitting glucose analogue
      18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody
      imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large
      cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore,
      there is a growing need for a clear definition of the relative position of PET
      within the currently available diagnostic modalities. Significant scientific data
      indicate that FDG-PET adds clinically useful information to the information
      obtained by standard means (mainly CT and endoscopic ultrasound) throughout the
      different phases of clinical patient management: 1) at initial diagnosis: PET
      detects more frequently distant lymph node involvement and organ metastases
      compared to conventional diagnostics, allowing a more accurate selection of the
      most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET
      allows early identification of non-responding patients. Indeed, the metabolic
      response as measured by serial FDG-PET can be used to predict the clinical and
      histopathological response. Moreover, the PET-response seems to be related to
      overall and disease free survival; 3) after a treatment: FDG-PET allows accurate
      assessment of the residual tumor load; 4) in the follow up: FDG-PET allows
      accurate detection and restaging of recurrent disease.

PMID- 15243408
TI  - Position of nuclear medicine modalities in the diagnostic workup of cancer
      patients: lung cancer.
AB  - This review summarizes the current literature and tries to define the status of
      nuclear medicine in the clinical workup of lung cancer patients. Nuclear medicine
      procedures and positron emission tomography (PET) with the EMEA-approved
      radiopharmaceutical fluorodeo-xyglucose (FDG) are indicated for the
      characterization of lung lesions; the nodal staging of non-small cell lung cancer
      (NSCLC); the detection of distant metastases; and for the diagnosis of recurrent
      disease. Recent studies have shown the clinical efficacy of nuclear medicine and
      especially of FDG-PET in the workup of lung cancer patients and its significant
      impact on patients' management. Conventional nuclear medicine procedures are
      established for the pre-therapeutic assessment of pulmonary perfusion and
      function (lung perfusion and ventilation scintigraphy) and for the detection of
      bone metastases (skeletal scintigraphy). In studies in thousands of patients, FDG
      PET has been proved to be the most accurate non-invasive diagnostic test for the
      characterization of lung nodules and masses. It can be recommended at least for
      patients with increased risk at surgery. FDG-PET should be applied in candidates
      for surgery of lung cancer, as mediastinoscopy may be omitted if PET shows no
      metastases in the mediastinum, and because FDG-PET avoids futile surgery by a
      more accurate selection of patients, especially by the detection of unexpected
      distant metastases. In candidates for thoracic radiotherapy, FDG-PET can help to
      exclude extrathoracic disease which needs systemic treatment and to better define
      the target volume for radiation therapy. The time has come for FDG-PET to find
      its place in new guidelines for the workup of lung cancer patients.

PMID- 15243409
TI  - Ovarian cancer management. Practice guidelines for nuclear physicians.
AB  - Ovarian cancer is a frequent and severe malignancy. Over 75% of cases are
      diagnosed at an advanced stage with disease spread beyond the ovaries. Despite
      the high response rates of initial treatments (i.e.,70-80%), the median
      progression-free survival of advanced ovarian cancer is 16-22 months, and the 5
      year overall survival, 20-30%. The majority of these patients relapse, with
      metastatic peritoneal spread, unresectable, or drug resistant disease. Our goal
      was to outline current knowledge about diagnosis, prognostic factors, and
      treatments, and to dwell on non-nuclear medicine and nuclear-medicine diagnostic
      procedures.

PMID- 15243410
TI  - Position of nuclear medicine techniques in the diagnostic work-up of
      neuroendocrine tumors.
AB  - In recent years nuclear medicine has contributed to the impressive development of
      the knowledge of neuroendocrine tumors in terms of biology (receptor
      scintigraphy), pharmacology (development of new tracers), and therapy
      (radiometabolic therapy). At present, it is impossible to plan the management of
      a patient affected by a neuroendocrine tumor without performing nuclear medicine
      examinations. The contribution of nuclear medicine had affected and improved the
      management of these patients by offering various important options that are part
      of the modern diagnosis and treatment protocols. The clinical experience and the
      literature confirm that, among the wide variety of tracers and nuclear medicine
      modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe
      octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use.
      Several new somatostatin analogues are under investigation. Positron emission
      tomography (PET) supplies a range of labelled compounds to be used for the
      visualization of tumor biochemistry. In addition to the first routinely used PET
      tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of
      radiopharmaceuticals based on different precursors such as fluorodopamine and 5
      hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the
      diagnosis of neuroendocrine tumors has to be based on integrated information
      derived from different examinations including nuclear medicine studies. The
      clinical presentation of neuroendocrine tumors is highly variable: sometimes they
      manifest typical or atypical symptoms but they may also be detected by chance
      during an X-ray or ultrasound examination carried out for other reasons. At
      disease presentation nuclear medicine modalities are sometimes able to direct
      physicians towards the clinical diagnosis thanks to the specificity of their
      imaging mechanisms. They also play a role in disease staging and restaging,
      patient follow-up and treatment monitoring. In addition, the biological
      characterisation of neuroendocrine tissues (receptor status, glucose metabolism,
      differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as
      a prognostic parameter and sometimes as a predictor of the response to treatment.

PMID- 15243411
TI  - The role of nuclear medicine in the diagnosis of cancer of unknown origin.
AB  - Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in
      biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies.
      These tumors have a specific biology with clinical characteristics of rapid
      progression and atypical metastases. Diagnostic evaluation is directed at the
      identification of treatable subset. Accurate diagnostic workup is crucial because
      both prognosis and survival rates depend mainly on detection of the primary tumor
      site. Although these patients undergo extensive imaging procedures, nuclear
      medicine techniques are under-utilized despite their ability of providing
      molecular information. Positron emission tomography has an emerging role in this
      clinical challenge along with other nuclear medicine methods including, bone
      scan, thyroid scintigraphy.

PMID- 15243412
TI  - Position of nuclear medicine modalities in the diagnostic work-up of breast
      cancer.
AB  - Breast tumors can be imaged by different modalities: mammography is the most
      widely used technique because of its diagnostic value, patient compliance and low
      costs. Some techniques such as ultrasound (US) are often indicated, while others,
      such as digital mammography and magnetic resonance imaging (MRI) are still under
      evaluation and seem to be very promising. Among the nuclear medicine techniques
      breast scintigraphy with (99m)Tc-labelled lipophilic cations (SestaMIBI or
      tetrofosmin), positron emission tomography (PET) with 18F-2-deoxy-2-fluoro-D
      glucose (FDG) have been evaluated in many clinical trials. At present breast
      scintigraphy has limited applications due to its poor spatial resolution, which
      has a minimum of 8 mm. It is questionable whether single photon emission
      tomography (SPECT) can offer any substantially better information on the breast;
      however, SPECT is more accurate in detecting axillary lymph nodes. Recent
      approaches using breast dedicated collimators and cameras have greatly improved
      the SPECT resolution and sensitivity. The most interesting technique offered by
      nuclear medicine today are PET and lymphoscintigraphy with the intraoperative
      detection of handled gamma probe. The sentinel node detection has achieved a
      large consensus of reliability and at present it has an important place in the
      clinical management. In the same time many authors have acknowledged the value of
      PET in the differential diagnosis of breast lesions and in locoregional staging,
      since breast cancer is strongly avid for glucose. PET demonstrated also its
      efficacy in detecting axillary lymph node metastases. Even in some clinical
      trials its accuracy proved nearly comparable to that of lymphoscintigraphy with
      sentinel node biopsy, other studies showed that PET scanning does not currently
      have adequate spatial resolution to detect both micro- and small macrometastatic
      disease in axillary lymph nodes. The added value of PET in breast cancer staging
      is that with a single examination PET allows the characterisation of breast
      lesions, in addition to complete viewing of the entire body. Whole-body PET may
      substitute other diagnostic assessments by examining the various regions of
      potential tumour spread. The current diagnostic work-up for pre- and
      postoperative staging includes various examinations: chest X-rays, US of the
      abdomen, mammography of the contralateral breast. Bone scintigraphy with (99m)Tc
      diphosphonates and laboratory tests can also be considered in women with large
      tumors or in symptomatic patients. Computed tomography (CT) and MRI may be used
      in order to resolve particular diagnostic problems. The current application of
      some of these modalities depends on the risk of the single patient of developing
      metastatic spread, which is revealed by a number of prognostic parameters of
      tumor aggressiveness and of course, clinical stage. Bone scintigraphy and PET may
      be useful in monitoring therapy response and in detecting tumour relapses during
      follow-up. In particular PET guided by tumor markers measurements shows to detect
      more lesions than other non nuclear medicine modalities.

PMID- 15243413
TI  - A novel treatment of hypermobile lateral meniscus with monopolar radiofrequency
      energy.
AB  - Orthopedic treatment with radiofrequency energy (RFE) was first used in shoulder
      surgery, and its effectiveness has been reported. The purpose of RFE treatment of
      soft tissue is to induce qualitative changes in collagen and obtain stability.
      Hypermobile lateral meniscus (HLM) is characterized by abnormal mobility
      resulting from rupture or defects of the popliteomeniscal fasciculi, but no
      satisfactory treatment has been reported. We followed up patients with HLM who
      underwent monopolar RFE treatment and confirmed its short-term effects by
      magnetic resonance imaging and second-look arthroscopy.

PMID- 15243414
TI  - Large lateral meniscal ganglion cyst extending into the intercondylar fossa of
      the knee.
AB  - We report the case of a 31-year-old, otherwise healthy man with a large intra
      articular meniscal ganglion cyst (27.7 x 13.5 mm) originating from the dorsal
      horn of the lateral meniscus. Clinically, the patient presented with knee pain in
      a squatting position. Magnetic resonance imaging revealed a large intra-articular
      cyst in the posterior compartment. At arthroscopic surgery, the ganglion cyst was
      found in the intercondylar space posteriorly to the posterior cruciate ligament.
      After removal of the ganglion cyst, a horizontal tear in the dorsal horn of the
      lateral meniscus was revealed and treated by partial meniscectomy. To our
      knowledge, a meniscal ganglion cyst originating from the lateral meniscus and
      extending into the joint is an extremely rare event, with only two previous
      reported cases. We review the current literature on the pathogenesis,
      distribution, and treatment of meniscal ganglion cysts.

PMID- 15243415
TI  - Medial meniscus anterior horn cyst: arthroscopic decompression.
AB  - Meniscus cysts are mostly seen with meniscus tears, and arthroscopic
      decompression of cysts is gaining great importance in their treatment. In this
      study, we present a medial meniscus anterior horn cyst without an accompanying
      tear in the meniscus. A 33-year-old male patient was seen with pain and a
      palpable mass in his right knee. He complained that the severity of the pain had
      increased over the previous year. After the clinical and radiologic examinations,
      a painless, fixed soft tissue mass averaging 4 x 5 cm was located just medial to
      tuberositas tibia. The cyst was decompressed arthroscopically. In the 18th month
      of follow up, the mass had totally disappeared and the patient had no pain.
      Medial meniscus cysts are seen nine times fewer than lateral meniscus cysts. They
      are mostly accompanied with meniscal tears. Total meniscectomy with arthrotomy,
      isolated cyst excision, cyst excision, and partial meniscectomy with arthrotomy
      and arthroscopic partial meniscectomy with cyst decompression are treatment
      modalities. Arthroscopic meniscal cyst decompression is an important treatment
      choice and should always be taken into consideration with low morbidity, short
      recovery period, low recurrence rate, preservation of range of motion, and
      permission for early mobilization and rehabilitation of the joint.

PMID- 15243416
TI  - Bilateral meniscal cysts of medial menisci occurring in a career soldier.
AB  - A young male career soldier presented with bilateral meniscal cysts of the medial
      menisci combined with a meniscal tear. This was confirmed by magnetic resonance
      imaging and was treated by arthroscopic procedures. An arthroscopic examination
      showed mucous fluid to be leaking from a torn portion of his left knee; however,
      no similar leaking was observed in his right knee. These arthroscopic results
      thus will support an etiology in which meniscal cysts occur as a result of an
      extrusion of synovial fluid through meniscal tears.

PMID- 15243417
TI  - Synovial cyst formation resulting from nonabsorbable meniscal repair devices for
      meniscal repair.
AB  - Several arthroscopic meniscal repair techniques and devices have been developed
      during the past decade. The Mitek Meniscal Repair System (Mitek, Ethicon,
      Norderstedt, Germany) is one of these devices. We report a case of synovial cyst
      formation after medial meniscus repair with a nonabsorbable Mitek Meniscal Repair
      System. The cyst in the right knee developed 5 months after the meniscus repair.
      After excision of the synovial cysts and removal of these devices, the mass and
      pain of the knee were relieved. To our knowledge, this is the first report of
      synovial cyst formation resulting from this device.

PMID- 15243419
TI  - Thromboembolic events after arthroscopic knee surgery.
AB  - We present a case of fatal pulmonary embolus after knee arthroscopy to raise
      awareness of the frequency of this complication and the need for consideration of
      thromboembolic prophylaxis before knee arthroscopy.

PMID- 15243418
TI  - Delayed biodegradation of a meniscal screw.
AB  - A biodegradable polylactide meniscal screw was removed 32 months after the
      original meniscal repair. It was then subjected to gel permeation chromatography
      and was found to have retained 64.7% of its original molecular weight. Although
      it is obvious that the manufacturers of biodegradable implants have succeeded in
      producing materials that retain their strength long enough to allow tissue
      healing, the question arises as to the true biodegradation time of the same
      implants.

PMID- 15243420
TI  - Arthroscopic treatment of an impinging mobile bearing in a unicompartmental knee
      arthroplasty.
AB  - We report a case of impingement between the mobile bearing of a unicompartmental
      knee arthroplasty and the edge of the tibial eminence. The diagnosis was
      confirmed and the impingement successfully treated arthroscopically.

PMID- 15243421
TI  - Arthroscopic resection of an intra-articular osteochondroma of the knee in the
      patient with multiple osteochondromatosis.
AB  - Osteochondroma is usually located outside of the joint and is asymptomatic. We
      have witnessed the symptoms of intra-articular osteochondroma of the knee joint
      and resected it arthroscopically. A 54-year-old woman with multiple
      osteochondromatosis presented with pain and a click on the right knee. Click was
      palpable and audible at the lateral aspect of the patellofemoral joint.
      Arthroscopy revealed that osteochondroma in the anterolateral site of the distal
      femur impinged the lateral edge of the lateral facets of the patella and the
      inflammatory change of the lateral capsule of the patellofemoral joint.
      Arthroscopic resection of this osteochondroma completely eliminated the symptoms.
      To our knowledge, this is the first report of arthroscopic resection of an
      osteochondroma in the intra-articular joint.

PMID- 15243422
TI  - Osteochondral grafting for cartilage defects in the patellar grooves of bilateral
      knee joints.
AB  - Autogenous osteochondral grafts have become popular recently for use in small,
      isolated, contained articular cartilage defects. We treated a 35-year-old man who
      had cartilage defects, which were the same shape and probably the result of
      overuse, in the patellar grooves of both knee joints. The left side was 30 x 25
      mm, and the right side was 17 x 17 mm in his right patellar groove, and 15 x 7 mm
      in his right medial femoral condyle. Therefore, we performed multiple
      osteochondral grafting of the bilateral lesions. Thirty-two months after his
      right knee operation (37 months after his left one), he had no pain or symptoms
      in his left knee and occasional mild pain and catching in his right knee. At
      second-look arthroscopy, the joint surface of the articular cartilage in the
      bilateral patellar groove was almost completely smooth. However, the whole of the
      weight-bearing area around the grafted plugs in the medial femoral condyle showed
      cartilage degeneration. Approximately 3 years after implantation of osteochondral
      grafts into similarly shaped cartilage lesions in the bilateral patellar grooves,
      the operative results were good. However, careful follow up is needed.

PMID- 15243423
TI  - Split-line pattern and histologic analysis of a human osteochondral plug graft.
AB  - The split-line pattern of collagen fibers in articular cartilage is oriented
      according to weight-bearing stresses. The importance of aligning the split-line
      pattern of articular cartilage in human osteochondral plug grafts relative to the
      surrounding cartilage has been proposed but not evaluated clinically. The purpose
      of this case report is to compare the articular split-line pattern with the
      histologic analysis of a specimen obtained from a patient who underwent an
      osteochondral plug transfer procedure with subsequent conversion to joint
      arthroplasty. The fresh osteochondral section obtained at total knee
      arthroplasty, including the area treated 18 months earlier with an osteochondral
      plug transfer, was fixed in formalin. Split-lines were demonstrated on the
      surface using a needle dipped in India ink. After decalcification and paraffin
      embedding, the specimen was sectioned and stained with Safranin O and fast green
      for histologic analysis. The split-line pattern of the anterior portion of the
      graft was oriented parallel to the resident cartilage; however, collagen
      orientation was divergent (approximately 30 degrees oblique) to the surrounding
      cartilage near the posterior portion of the graft. It was at this margin that
      further resident articular degeneration was noted despite the plug articular
      surface remaining relatively intact. Although bony incorporation of the plug
      occurred, there was a residual chondral cleft at the graft-host interface. Our
      report suggests that an osteochondral plug transfer can survive despite a
      slightly divergent collagen split-line pattern of plug relative to the resident
      articular bed. Perhaps more important to the clinical outcome is the selection of
      true focal, traumatic lesions rather than lesions degenerative in etiology, no
      matter how focal they appear.

PMID- 15243424
TI  - Allograft maturation in anterior cruciate ligament reconstruction.
AB  - This case report describes the histologic incorporation of a freeze-dried
      Achilles tendon allograft used for arthroscopic anterior cruciate ligament (ACL)
      reconstruction. The patient had regained stability from the procedure but had
      worsening pain over the medial compartment. The patient underwent total knee
      arthroplasty 2.5 years after ACL reconstruction. The surgeon was able to observe
      the graft in situ and examine the histology of the graft tunnel interface. This
      interface demonstrated Sharpey's fibers.

PMID- 15243425
TI  - Irreducible posterolateral knee dislocation resulting from a low-energy trauma.
AB  - A small amount of knee dislocations is included in the irreducible knee
      dislocations group. In such instance, medial femoral condyle is buttonholed
      through the gap formed by medial retinacular and capsular structures and this
      prevents reduction. In this study, we present two cases in which there were
      irreducible posterolateral knee dislocations resulting from a low-energy trauma.
      In both cases, dimple sign produced by the invagination of the medial retinacular
      structures and capsule and ecchymosis medially were noted. Soft tissue
      invaginated between the trochlea and intercondylar notch was extracted by open
      reduction.

PMID- 15243426
TI  - Intra-articular ganglia arising from the posterior joint capsule of the knee.
AB  - Magnetic resonance imaging (MRI) is an effective method to evaluate cystic
      lesions of the knee. Intra-articular ganglia of the knee joint was considered to
      be rare before the advent of MRI. However, because an MRI is often used to
      diagnose knee pathology, the reported prevalence of intra-articular ganglia has
      increased. We describe two cases of an intra-articular ganglion arising from the
      posterior joint capsule. Both cysts appeared to be arising from the posterior
      cruciate ligament by both MRI as well as arthroscopy through a lateral
      infrapatellar portal. However, arthroscopy through a posteromedial portal
      revealed the cysts to originate from the posterior joint capsule. It suggests
      that some of the ganglion arising from the posterior cruciate ligament reported
      in the literature might actually be from the posterior joint capsule. To prevent
      recurrence of a ganglion cyst, when preoperative MRI shows the mass to be located
      posterior to the cruciate ligaments, we recommend that the relationship of the
      ganglion cyst to the posterior joint capsule be evaluated at arthroscopy through
      the posteromedial or posterolateral portal.

PMID- 15243428
TI  - Arthroscopic treatment of an avulsion fracture of the ligamentum teres of the hip
      in an 18-year-old horse rider.
AB  - We present the case of an 18-year-old horse rider with an avulsion fracture of
      the ligamentum teres causing persistent hip pain and locking for 2 years. The
      patient had no history of major trauma; however, repeated minor hyperabduction
      injuries occurred. We were able to successfully treat this patient by
      arthroscopic removal of the bony fragments and two loose bodies and partial
      resection of the ligamentum teres.

PMID- 15243427
TI  - Arthroscopic Keller technique for Freiberg disease.
AB  - Freiberg disease is a disorder that has a predilection for the second metatarsal
      head. Keller excision of the base of the proximal phalanx is a procedure
      described for the treatment of late-stage Freiberg disease. We describe a case of
      a 60-year-old man, with a stage IV lesion according to Smillie's classification,
      treated by debridement, removal of the free body, and arthroscopic Keller
      excision. Arthroscopic treatment allows the patient to begin and maintain an
      aggressive postoperative physical therapy program immediately after surgery, thus
      decreasing the risk of scarring and contracture. At last evaluation, 2 years
      postoperatively, he is symptom-free. A suggested pattern of minimally invasive
      surgery management of this disease is proposed.

PMID- 15243429
TI  - Pseudoaneurysm after interscalene block for a rotator cuff repair.
AB  - We present a case of a 68-year-old female patient who had an interscalene nerve
      block (ISB) complicated by compression of her brachial plexus by a
      pseudoaneurysm. The complication occurred after the patient received an ISB as
      anesthesia for an outpatient shoulder procedure. Review of this complication
      should alert surgeons to consider this diagnosis as a possibility in patients
      with postoperative pain and/or neurologic compromise after receiving an ISB.

PMID- 15243430
TI  - Complete, superior labral radial tear and type II slap tear associated with
      greater tuberosity fracture.
AB  - This case report presents a unique variant of superior labral-bicep complex
      injury. The combination of a complete anterior-superior radial tear of the labrum
      and bicep anchor instability has not been described in previous classifications
      of these injuries. The injury was traumatic in nature and was associated with a
      displaced fracture of the greater tuberosity. The labral pathology was treated by
      an anatomic repair technique as described. Rationale for the repair performed, as
      well as implications of the injury treated by debridement alone, are discussed.
      Clinicians should be aware of different patterns of superior labral-bicep complex
      injuries and the implications on function and stability of the glenohumeral
      joint.

PMID- 15243431
TI  - Arthroscopic repair of a posterior humeral avulsion of the inferior glenohumeral
      ligament (HAGL) lesion.
AB  - Recently, the humeral avulsion of the inferior glenohumeral ligament (HAGL) has
      been described as a cause of shoulder instability. All documented cases in the
      literature describe the avulsion as an anterior and lateral disruption leading to
      anterior instability. We detail a previously unreported case of a HAGL lesion
      involving the posterior band of the inferior glenohumeral ligament. Arthroscopic
      reattachment using an additional posteroinferior portal resulted in a successful
      repair.

PMID- 15243432
TI  - Rupture of the biceps tendon after arthroscopic thermal capsulorrhaphy.
AB  - The use of thermal energy in the shoulder to tighten capsular tissues through
      collagen denaturation is well established. Although reported complication rates
      are low, the natural history of thermal manipulation to both target and
      collateral tissue is poorly defined. We report two cases of biceps tendon rupture
      after arthroscopic capsular shrinkage. Both patients were young, athletic men
      with normal long head biceps tendons at the time of surgery. Each patient
      experienced a complete tear of the long head with distal muscle retraction,
      resulting in a "Popeye" deformity, at 3 months postoperatively. One patient
      elected further surgery with biceps tenodesis. Both patients have returned to
      their athletic activities with minimal functional deficits.

PMID- 15243433
TI  - Biceps pulley impingement.
AB  - We present three cases of a detached biceps pulley, which impinges on
      posterosuperior glenoid labrum.

PMID- 15243434
TI  - Complications of thermal ablation in wrist arthroscopy.
AB  - Wrist arthroscopy is a valuable diagnostic and therapeutic tool. Thermal ablation
      can be used concomitantly to treat partial ligamentous tears, triangular
      fibrocartilage cartilage complex tears, and to perform partial synovectomy. We
      reviewed 47 consecutive patients who underwent wrist arthroscopy with concomitant
      thermal ablation between 1997 and 2001. Three patients sustained serious
      complications. The serious complications included, in all three patients, tendon
      ruptures and in one case, a 5 x 10-mm full-thickness skin burn. Thermal treatment
      of collagenous tissues has recently gained popularity in the orthopedic
      literature, but there is little information on the potential complications. The
      arthroscopist of large and small joints must be aware of the risks involved when
      using thermal ablation.

PMID- 15243435
TI  - All-arthroscopic removal of a suture anchor using an arthroscopic bur sheath.
AB  - Suture anchors are commonly used in shoulder repairs, especially arthroscopically
      performed repairs. Anchors can become prominent and require removal. We describe
      a technique of arthroscopic anchor removal using a bur sheath.

PMID- 15243436
TI  - Arthroscopic reduction and percutaneous fixation of a radial neck fracture in a
      child.
AB  - Radial neck fractures are frequent lesions in the developing elbow. For important
      angular displacement higher than 60 degrees, there are several alternative
      treatments. We present an unpublished technique of reduction with arthroscopic
      assistance and percutaneous stabilization that allows one to perform direct
      pressure to the radial head, better intra-articular evaluation, reduction
      control, with minimal soft tissue lesion, and reduce the need for intraoperative
      fluoroscopy.

PMID- 15243437
TI  - Minimally invasive transrotator cuff approach for arthroscopic stabilization of
      the posterosuperior glenoid labrum.
AB  - We describe a novel technique for repair of the superior glenoid labrum posterior
      to the biceps anchor. This approach optimizes access for fixation of the superior
      and posterosuperior labrum, but involves significantly less trauma to the rotator
      cuff and subacromial space compared with previously described transrotator cuff
      methods. We suspect that the relative lack of trauma to the rotator cuff and
      subacromial space accounts for the superior clinical scores and lower incidence
      of postoperative impingement symptoms with this technique compared with
      previously reported transrotator cuff methods.

PMID- 15243438
TI  - How to use cuff suture instruments: the concept of "concave in and concave out".
AB  - Arthroscopic reconstructive surgery of the shoulder is extremely demanding. The
      advent of suture anchors and knot-tying instruments has greatly facilitated its
      development. Knowledge of the anatomy and surgical principles alone is not
      enough. Familiarity with specific instruments is also important. We describe our
      experience with the Elite Cuff Stitch Suture Relay (Smith & Nephew, London,
      U.K.). We describe a new concept on how to use this suture passer or similar
      instrument. We advocate this new concept of "concave in and concave out."

PMID- 15243439
TI  - Preoperative ultrasonographic-guided marking of calcium deposits in the rotator
      cuff facilitates localization during arthroscopic surgery.
AB  - A new technique using a marking needle (Accura; Medical Device Technologies,
      Gainesville, FL) placed under ultrasonographic guidance preoperatively in a
      calcific deposit in the rotator cuff of the shoulder is described. When standard
      subacromial bursoscopy is performed, the needle is visualized in the bursa and
      followed to its position in the deposit. The deposit is opened and removed.

PMID- 15243440
TI  - Arthroscopic rotator interval repair: the three-step all-inside technique.
AB  - Many clinical reports have emphasized the importance of rotator interval lesions
      in patients with glenohumeral instability, and many investigators have described
      open repair techniques, either as a supplement to other capsule reconstruction or
      as an isolated procedure. In this article, an original arthroscopic technique for
      rotator interval closure is described. This technique allows the operator to
      accurately manage the degree of tightening of the rotator interval, the knot
      tying, and the suture cutting, under direct intra-articular arthroscopic vision.

PMID- 15243441
TI  - Arthroscopic posterior portal closure.
AB  - Posterior "working" portals in arthroscopic posterior stabilization could result
      in defects of the posterior capsule if not repaired. We describe a single portal
      technique used to close the posterior portal defect after arthroscopic
      stabilization. It is a safe and easy-to-perform technique, which could strengthen
      the structural integrity of the repair.

PMID- 15243442
TI  - The modified beachchair position for arthroscopic shoulder surgery: the La Jolla
      beachchair.
AB  - Arthroscopic surgery of the shoulder is usually performed in the lateral
      decubitus or beachchair position. The modified beachchair position described here
      allows arthroscopic procedures to be performed as in the lateral position yet
      maintains a semiupright orientation and permits conversion to open procedures as
      in the beachchair position. The results of this technique are reported for 50
      consecutive patients with a variety of diagnoses. This modified beachchair
      position was found to be quickly and easily accomplished with a minimum of
      special equipment.

PMID- 15243443
TI  - Arthroscopic Bankart repair in the beachchair position: a cannulaless method
      using an intra-articular suture relay technique.
AB  - In shoulder arthroscopy, cannulas with large diameters (7-9 mm) are commonly used
      both in the lateral decubitus and the beachchair position because they ensure the
      easy introduction of instruments into the intra-articular space and provide a
      clear arthroscopic view through the application of high intra-articular pressure.
      On the other hand, fluid extravasation and the resulting inconvenience due to the
      narrowing of the intra-articular working space are also obvious issues.
      Consequently, this makes arthroscopic stabilization surgery all the more
      challenging. To avoid these shortcomings of this procedure, we believe cannulas
      should be used only when necessary such as for knot tying and for transtendon
      portals. In this article, we report a unique and original method of arthroscopic
      Bankart repair in the beachchair position with limited use of cannulas of smaller
      diameter (5 mm) and its advantages over ordinary arthroscopic techniques using
      large-diameter cannulas in terms of preventing fluid extravasation and keeping a
      wide working space, which facilitates beneficial intra-articular techniques.

PMID- 15243444
TI  - Modified technique for arthroscopic Bankart repair using anchor sutures.
AB  - Bankart repair, or one of its modifications, is currently the gold standard
      procedure for treatment of anterior traumatic shoulder instability. It is now
      possible to perform the operation arthroscopically with the introduction of
      suture anchors. As described by Eugene Wolf, arthroscopic shoulder stabilization
      using the Mitek (Mitek Surgical Products, Ethicon, Edinburgh, U.K.) anchors
      requires two anterior portals and intra-articular knot tying. However, sliding
      the anchor on the inside limb of a suture loop could be challenging because the
      other limb could get tangled in the nitinol arc of the anchor. We describe a
      modification of the original technique to prevent that possibility and avoid any
      tension on the repair tissue during anchor passage. The proposed modification
      involves the use of a cheap, readily available silastic feeding tube to isolate
      the outside limb of the suture loop and stabilize labral tissues while the anchor
      is being passed. This tube also serves as a stent for knot tying. By allowing the
      whole operation to be performed through one anterior portal, the modified
      technique reduces possible morbidity associated with a second portal and further
      reduces cost.

PMID- 15243445
TI  - Lasso repair of SLAP or Bankart lesions: a new arthroscopic technique.
AB  - Restoring the anatomic position and securing a torn superior labrum or Bankart
      lesion to its bony bed on the superior or anterior glenoid is the objective of
      surgical repair. The following technique describes a method that we have found to
      be effective, reproducible, and more time-efficient in affecting this goal. This
      technique allows the sutures to be passed through the soft tissue in a single
      step and, in addition, makes suture management easier before knot tying.

PMID- 15243446
TI  - Superior labrum anterior posterior (SLAP) repair using the Neviaser portal.
AB  - Superior labrum anterior posterior (SLAP) repair using suture anchors requires
      successful passing of sutures through the labrum. The optimal angle for passing a
      penetrating suture retriever is perpendicular to the superior labrum. The
      Neviaser (superior-medial) portal, without a cannula, is ideally suited for this
      procedure. The authors demonstrate their technique and review the anatomy of this
      portal. The Neviaser portal is illustrated as an important working portal and not
      merely for inflow or outflow. The authors demonstrate that this is a safe and
      easy technique for SLAP repair.

PMID- 15243447
TI  - Arthroscopic humeral avulsion of the glenohumeral ligaments (HAGL) repair.
AB  - Humeral avulsion of the glenohumeral ligaments (HAGL lesion) is one of the
      pathologic lesions that occurs secondary to anterior glenohumeral instability.
      Although HAGL lesions occur less commonly than Bankart lesions in cases of
      anterior instability, it is necessary to understand this pathology and to make
      the necessary repair. An all-arthroscopic technique using suture anchors can be
      used to repair HAGL lesions, but it is a difficult and demanding technique. To
      facilitate this type of repair, the surgeon must be: (1) comfortable with both
      the 30 degrees and 70 degrees arthroscopes, (2) able to establish and use the 5
      o'clock portal, (3) able to abduct and externally rotate the arm, and (4) able to
      ensure secure fixation of the glenohumeral ligaments to bone through adequate
      knot and loop security.

PMID- 15243448
TI  - Ultrasonography for intraoperative control of the amount of bone resection in
      arthroscopic acromioclavicular joint resection.
AB  - Remaining superior osteophytes or osseous spurs after arthroscopic lateral
      clavicle resection can cause persistent pain and could lead to revision surgery.
      A new method of intraoperative ultrasonographic imaging of the result of the
      operation during arthroscopic lateral clavicle resection is presented. In 10
      patients with acromioclavicular arthritis, standardized arthroscopic lateral
      clavicle resection was performed. Intraoperatively, the space between the
      clavicle and the acromion was measured before and after arthroscopic
      acromioclavicular resection using a Sonosite 180 plus (SonoSite, Bothell, WA)
      with a 10-MHz broadband linear array in a sterile bag. The width of the joint
      space between the clavicle and the acromion was between 0.38 and 0.56 cm before
      operation and 0.92 cm and 1.28 cm after operation (nine cases). In one case, the
      anticipated minimum resection of 0.5 cm was not achieved at the sonographic
      measurement and further resection was required. Real-time ultrasonography allows
      exact measurement of the amount of resected bone during arthroscopic lateral
      clavicle resection. This could avoid revision surgery resulting from persisting
      disability caused by insufficient or extensive bone resection.

PMID- 15243449
TI  - Arthroscopic resection for the unstable inferior leaf of anterior horn in the
      horizontal tear of a lateral meniscus.
AB  - The unstable inferior leaf of the anterior horn in the horizontal tear of the
      lateral meniscus is a challenging lesion to the arthroscopist. However, there are
      no devices for it and no proper procedures are introduced. We describe a new
      arthroscopic technique of partial meniscectomy by using three portals. This
      technique uses a unique portal, extreme far anteromedially.

PMID- 15243450
TI  - Arthroscopic posterior cruciate ligament tibial inlay reconstruction.
AB  - Tibial inlay posterior cruciate ligament (PCL) reconstruction was developed to
      avoid "killer turn" of the tibial tunnel. It requires a surgical dissection to
      popliteal fossa and changing of the patient's position during operation. We
      report an arthroscopic tibial inlay PCL reconstruction technique to avoid
      morbidity from an open procedure. Achilles tendon-bone allograft was used for
      reconstruction, and bone plug was designed in a cylindrical shape vertical to the
      tendon direction for tibial fixation. The intra-articular length of PCL is
      measured, and the proximal graft is prepared with a whipstitch and an EndoPearl
      (Linvatec, Largo, FL) is connected for enhancing femoral fixation. After tibial
      graft fixation with an absorbable interference screw, tibial site fixation was
      reinforced with suture anchoring to a washer on the anterolateral surface of the
      tibia. Femoral fixation was done with another screw. It was possible to reproduce
      the original concept of PCL tibial inlay graft with our arthroscopic technique.

PMID- 15243451
TI  - An accessory portal for posterior cruciate ligament tibial insertion
      visualization.
AB  - Posterior cruciate ligament (PCL) reconstruction is infrequently performed,
      technically challenging, and has less predictable results compared with its
      anterior cruciate ligament (ACL) counterpart. Creation of a transtibial tunnel
      has been associated with catastrophic neurovascular complications, as well as
      tunnel malpositioning. This technical note reports the use of the femoral PCL
      tunnel to visually access the posterior slope for tibial tunnel creation. This
      technique modification allows concurrent placement of instruments through an
      inferomedial and/or posteromedial portal to facilitate PCL insertional
      debridement, placement of the tibial aimer, and creation of the tunnel. We feel
      that this technical modification provides superior visualization of this anatomic
      area.

PMID- 15243452
TI  - Posterolateral corner reconstruction using a hamstring allograft and a
      bioabsorbable tenodesis screw: description of a new surgical technique.
AB  - Capsuloligamentous posterolateral corner knee joint deficiencies cause increased
      anterior cruciate ligament forces during internal knee rotation and increased
      posterior cruciate ligament forces during external knee rotation. Undiagnosed
      posterolateral corner knee joint injury in combination with anterior cruciate
      ligament or posterior cruciate ligament injury can lead to failure of anterior
      cruciate ligament or posterior cruciate ligament reconstruction. The purpose of
      this technical note is to present a new posterolateral corner reconstruction
      technique for treating patients with chronic capsuloligamentous posterolateral
      corner deficiency. The technique uses a bioabsorbable tenodesis screw and a
      hamstring allograft to reconstruct the popliteofibular and lateral collateral
      ligaments.

PMID- 15243453
TI  - Transtibial tubercle fixation without hardware for anterior cruciate ligament and
      posterior cruciate ligament reconstruction: A new technique.
AB  - Tibial fixation with implants for both anterior and posterior cruciate ligament
      reconstructions (ACLR and PCLR) can be associated with a wide variety of
      problems. Common problems encountered include graft-tunnel mismatch when using
      grafts with bone blocks, graft damage or poor graft fixation using metal or
      absorbable implants, painful retained hardware requiring removal, and hardware
      interference during revision surgery. A new technique is presented using
      transosseous graft suture passage across the tibial tubercle followed by knot
      tying over a bone bridge. The technique provides a quick, simple, safe, and
      reproducible alternative for primary or supplemental tibial graft fixation
      without hardware in ACLR and PCLR.

PMID- 15243454
TI  - Allograft bone augmentation in anterior cruciate ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction is a commonly performed procedure
      associated with predictable results in most patients. Intraoperative and
      postoperative complications can occur in up to 20% of surgeries and could result
      in the need for revision procedures. The following technical report describes the
      use of allograft corticocancellous bone for supplemental interference fixation of
      a bone-patellar tendon-bone ACL autograft within a tibial tunnel in which
      anterior widening occurred as a complication of reaming. This technique was used
      to obtain and improve aperture outlet fixation of the autograft within the tibial
      tunnel while maintaining adequate position and tension on the ACL graft-fixation
      construct. Clinical follow up at 36 months has revealed radiographic
      incorporation of the allograft into the tibial tunnel as well as optimal
      subjective, objective, and functional outcomes as measured by patient response,
      physical examination, and serial KT-1000 (MEDmetric, San Diego, CA) arthrometer
      data. This technique could be useful in revision cases in which tunnel
      enlargement and/or widening is noted.

PMID- 15243455
TI  - Modified inside-out technique for meniscal repair.
AB  - A modified technique of the inside-out suture for arthroscopic repair of meniscus
      is described. Although the conventional inside-out technique is a fine modality
      of a meniscal repair, it is difficult to perform vertical suture and to attain
      good coaptation and strong fixation. We introduce a modified inside-out suture,
      which uses a suture hook, a zone-specific cannula, and a specially designed
      looped needle for an efficient meniscal repair. The modified inside-out suture
      technique provides vertically oriented suture, excellent tissue coaptation, and
      firm fixation. We recommend this technique as an excellent method for repairing a
      tear in most parts of the meniscus, especially the posteromedial corner.

PMID- 15243456
TI  - A simplified arthroscopic outside-in meniscus repair technique.
AB  - A simple and reproducible technique for meniscus tear repair is described. The
      technique requires the use of a 16-gauge intravenous catheter, a suture hook, and
      a knot pusher. The catheter is used for perforation of the meniscus and the tear
      site in two adjacent locations, then the two free suture ends are retrieved and
      passed along a small arthroscopic cannula placed at the ipsilateral joint space,
      and finally a sliding arthroscopic knot is tied and advanced to the meniscus
      surface with a knot pusher. This simple technique provides secure fixation of the
      meniscus tear during the healing period and has been proven successful and
      without complications in the patients in whom it has been used.

PMID- 15243457
TI  - Arthroscopic treatment of the arthrofibrotic knee.
AB  - The management of motion loss of the knee is challenging. A clear understanding
      of the pathoanatomic causes of motion loss is necessary to establish a careful
      and rational approach to treatment. Early recognition and physical therapy are
      effective for the majority of patients, but when these conservative measures
      fail, operative intervention is indicated. The purpose of this article is to
      outline a comprehensive approach to the arthroscopic evaluation and treatment of
      the arthrofibrotic knee. This technique is designed to allow the surgeon to
      systematically address the numerous causes of motion loss of the knee.

PMID- 15243458
TI  - New technique for chronic posterolateral instability of the knee: posterolateral
      reconstruction using the tibialis posterior tendon allograft.
AB  - Posterolateral instability of the knee is known as one of the most challenging
      injuries. Although several procedures have been designed for the posterolateral
      instability, there is no gold standard management as yet. We present a technique
      for posterolateral instability of the knee using a tibialis posterior tendon
      allograft, which reconstructs the lateral collateral ligament and popliteal
      tendon with its attachment to the tibia. This can correct not only varus, but
      also external rotary instability.

PMID- 15243459
TI  - Arthroscopic-assisted biceps tenodesis for ruptures of the long head of biceps
      brachii: The cobra procedure.
AB  - A number of open procedures have been presented in the literature that described
      the repair of the ruptured long head of biceps brachii (LHBB). Although
      arthroscopic biceps tenodesis techniques have been used to address partial tears
      or subluxation of the biceps, no arthroscopic technique to assist in the
      treatment of complete retracted ruptures of the LHBB has been described. This
      article describes an arthroscopic-assisted biceps tenodesis, using interference
      screw fixation, in the treatment of acute or chronic LHBB ruptures. An
      arthroscopic-assisted biceps tenodesis with interference screw fixation provides
      an alternative to open LHBB tenodesis. The ability to tenodese the retracted LHBB
      arthroscopically is a technologic advance that could reduce morbidity in
      comparison to open tenodesis, thus resulting in a better functional outcome.

PMID- 15243460
TI  - Simplifying arthroscopic suture retrieval with a knot pusher.
AB  - The author describes a technique for simplifying suture retrieval during
      arthroscopic procedures. During retrograde suture retrieval, it might be
      difficult to grasp sutures unless the suture is brought to the retrieving
      instrument. If the surgeon does not have an assistant with arthroscopic
      experience, guiding the suture to the retriever could be impossible. Using a
      closed-end knot pusher, the assistant can easily deliver the suture to the
      retriever. This technique allows even the least experienced arthroscopists to
      assist with suture retrieval.

PMID- 15243461
TI  - The private practice of oral and maxillofacial pathology--expanding career choice
      options.

PMID- 15243462
TI  - A mandibular central lesion with unusually rapid growth.

PMID- 15243463
TI  - Obesity and the practice of oral and maxillofacial surgery.
AB  - OBJECTIVES: Obesity is a disease that affects approximately 51 million Americans.
      The purpose of this paper is to establish the frequency of overweight and obese
      patients in an urban inner city oral and maxillofacial surgery (OMS) center, to
      provide an overview of the commonly applied standards and methods of establishing
      obesity, and to discuss the clinical and surgical implications that obesity has
      on the dispensing of office oral and maxillofacial surgical and anesthetic care.
      STUDY DESIGN: Consecutive patients presenting with oral and maxillofacial health
      needs were routinely screened for sex, age, blood pressure, pulse, height, and
      weight. Body Mass Index (BMI) was calculated in pounds using a standard
      mathematical formula for adults. Comparative statistical methods were used to
      depict the data. RESULTS: The study included 520 patients. The average age of all
      patients was 34.55 years, average height was 66.58 inches, and average weight was
      176.71 lbs with an average BMI of 28.5. One hundred ninety-four females (67%)
      were recorded as overweight and 130 females (45%) were recorded as obese
      (BMI>30). Fewer males were overweight (55%) or obese (25%). CONCLUSIONS: Sixty
      five percent of the patients observed in this study were judged as overweight or
      obese compared to a national average of 61%. Females of all ages were more likely
      to be overweight or obese compared to males. The complexities of treating a
      substantial number of obese patients in an OMS practice deserve more study.

PMID- 15243464
TI  - Analysis of soft tissue profile changes after mandibular advancement surgery.
AB  - The aim of this study was to analyze changes in soft tissue profile after
      mandibular advancement surgery, with special emphasis on the effect of skeletal
      relapse and different Class II facial patterns. The cephalometric radiographs of
      30 consecutive patients (24 women and 6 men, mean age 23 years) who underwent
      sagittal split osteotomy were studied. The radiographs were taken immediately
      before operation, at one week and 14 months postoperatively. To analyze the
      possible influence of hyper- and hypodivergent facial patterns, the patients were
      classified into low- (4 patients), medium- (16 patients) and high-angle (10
      patients) groups according to the magnitude of the mandibulonasal plane angle.
      The main movement occurred in the horizontal plane. Soft tissue pogonion and
      mentolabial fold were found to follow the underlying skeletal structures in a
      nearly 1:1 ratio. On final follow-up, skeletal relapse of 1.3 mm was measured at
      B-point and of 1.5 mm at pogonion. Taking the skeletal relapses into account, the
      ratios of both corresponding soft tissue references (alternative ratios) dropped
      to 60%. Soft tissue pogonion is the most reliable reference for the planning of
      mandibular advancement. The ratio of soft tissue movement to final skeletal
      position at the chin amounts to 60% for a realistic prediction. However, the low
      angle group differed from other groups by showing a markedly low soft-to-hard
      tissue ratio of only 14% at pogonion and a high ratio of 109% at the mentolabial
      fold. However, these differences in ratios between the groups were statistically
      not significant.

PMID- 15243465
TI  - Anxiety measurements in university students undergoing third molar extraction.
AB  - OBJECTIVE: This investigation was conducted to quantitate the anxiety associated
      with third molar extraction in university students, and to compare the measured
      anxiety before and after extraction and between men and women, first and second
      extraction, and impacted versus nonimpacted tooth extraction. STUDY DESIGN: The
      Japanese version of The State-Trait Anxiety Inventory (STAI), a psychological
      test, was given to 108 students undergoing third molar extraction. The students
      completed the test on the first examination (day 1), immediately before the
      extraction (day 2), and the day after the extraction (day 3). RESULTS: The state
      anxiety (STAI-S) score showed no significant difference between days 1 and 2, but
      the score on day 3 was lower than that on day 1, with a decrease in cases with a
      stage IV or V. Women showed more anxiety state on day 2 than men. The anxiety
      score on days 2 and 3 for the second extraction were significantly lower than
      those for the first extraction in 43 students who underwent third molar
      extractions twice. The change in the trait anxiety (STAI-T) stage was
      unremarkable among days 1, 2, and 3. No statistical difference was found in the
      anxiety between students undergoing impacted and nonimpacted third molar
      extraction. CONCLUSIONS: The anxiety status of students undergoing third molar
      extraction could be quantitatively evaluated using the STAI. The results of this
      investigation may provide oral maxillofacial surgeons with useful information
      about patients' anxiety throughout the tooth removal process.

PMID- 15243466
TI  - Backward distraction osteogenesis of condylar segment in patient with mandibular
      ramus deficiency--report of a case.
AB  - A backward distraction osteogenesis (BDO) of the condylar segment for treatment
      of mandibular ramus deficiency was developed. This report describes the clinical
      progress of a patient with mandibular ramus deficiency in whom satisfactory
      occlusion was achieved and maintained by gradual posterosuperior repositioning of
      the displaced condyles into the glenoid fossae during intermaxillary fixation.
      Findings of pre- and postoperative clinical and magnetic resonance imaging
      indicate that the effect of BDO on the temporomandibular joint was negligible.

PMID- 15243467
TI  - Canalicular adenoma of the palate: case report and literature review.
AB  - Canalicular adenoma is a rare benign salivary gland tumor of the oral cavity,
      typically located in the upper lip and buccal mucosa and infrequently found on
      the palate. The tumor is usually confined to soft tissue and rarely presents with
      bone erosion. A case of a large and locally-aggressive palatal canalicular
      adenoma is presented. The lesion presented herein was an asymptomatic ulcerated
      mass with significant bone erosion. The tumor was managed surgically with
      excision and reconstruction of the resulting palatal defect with a full
      temporalis muscle flap.

PMID- 15243468
TI  - Extraoral inverted teeth eruption: a case report.
AB  - A 14-year-old female presented with extraoral inverted eruption of left
      mandibular permanent molars 18 and 19 at the lower left inferior border of the
      mandible. Both the teeth started erupting 1 year after an extraoral surgical
      intervention for a discharging sinus 6 years ago. The subsequent eruption to the
      extraoral position of the permanent molars at the inferior border of mandible may
      be the result of the previous surgical procedure or pathology related to the
      abnormally positioned teeth. This case presents an infrequent complication
      affecting the adjacent permanent teeth.

PMID- 15243469
TI  - Isolation of non-tuberculosis mycobacteria in treated dental unit waterlines.
AB  - OBJECTIVE: The purpose of the study was to investigate the presence of non
      tuberculosis mycobacteria (NTM) in dental unit waterlines that were being
      routinely treated with an intermittent use waterline cleaner. STUDY DESIGN: The
      study was conducted at a hospital dentistry clinic where immunocompromised
      patients are seen. Water samples from two lines on one of two dental units were
      taken before and after routine weekend chemical treatment. Sampling was repeated
      on two subsequent occasions, on the same unit, at three monthly intervals.
      Laboratory techniques included centrifugation and membrane filtration to detect
      small numbers of organisms. RESULTS: Mycobacterium simiae was isolated from one
      of the four pre-treatment samples and from two of the four post-treatment
      samples. Mycobacterium mucogenicum was isolated from one of the four post
      treatment samples. CONCLUSIONS: This pilot study found that NTM were present in
      DUWLs that were being routinely treated with an intermittent use chemical
      cleaner. Practitioners are urged to understand the limitations of available DUWL
      treatments, and to consider the use of sterile water for non-surgical, as well as
      surgical, treatment of immunocompromised patients.

PMID- 15243470
TI  - Double-blind randomized, placebo-controlled study of pilocarpine to salvage
      salivary gland function during radiotherapy of patients with head and neck
      cancer.
AB  - OBJECTIVE: The efficacy of pilocarpine given during radiotherapy for head-neck
      cancer to reduce xerostomia was assessed. STUDY DESIGN: 58 patients receiving
      5000 cGy radiotherapy (RT) involving salivary glands bilaterally were selected at
      the Jewish General Hospital, Montreal, Canada. Patients were randomly assigned to
      pilocarpine (5 mg, PILO, n=29) or placebo group (PLA, n=29). These drugs were
      taken 5 times daily during radiotherapy (first study phase) and 4 times daily for
      5 weeks thereafter (second study phase). Saliva was collected and estimated for
      not stimulated and stimulated patients using the SAXON method. RESULTS: At the
      conclusion of the first phase, PILO patients reported a better global quality of
      life (P=.02) and less oral discomfort (P=.001) when compared to PLA. No
      significant difference was noted in the level of saliva, xerostomia, and other
      symptoms between patients in PILO and PLA. At the end of the second phase, a
      difference between groups was observed only for xerostomia and mucosal pain; both
      were significantly higher in PILO when compared to PLA (P <.05). CONCLUSION:
      Pilocarpine 5mg given 5 times daily did not appear to improve the production of
      saliva and global quality of life assessments, nor to decrease the symptoms of
      xerostomia 5 weeks after completion of RT in patients who were taking pilocarpine
      post-RT. There was a slight improvement in the quality of life and a decrease in
      the level of discomfort noted only after the first study phase. The limitations
      of this study are discussed.

PMID- 15243471
TI  - Denture stomatitis: a role for Candida biofilms.
AB  - OBJECTIVE: To assess the contribution of Candida biofilms to the etiology of
      denture stomatitis. STUDY DESIGN: Samples of denture acrylic were retrieved from
      patients with denture stomatitis and subjected to scanning electron microscopy
      (SEM) analysis. Oral swab and swish samples were taken from the same group of
      patients and representative C albicans isolates recovered were used to
      investigate the kinetics of biofilm development in vitro. RESULTS: Candida
      biofilms could be visualized by SEM directly from denture samples from patients
      with denture stomatitis. These biofilms showed a propensity to adhere along
      cracks and imperfections of the denture acrylic. C albicans clinical isolates
      were able to form biofilms in vitro, although differences in the extent of
      biofilm formation were observed for different isolates recovered from the same
      patient. Susceptibility testing indicated that the resulting biofilms showed
      increased resistance to antifungal treatment. Presence of serum and saliva
      conditioning films increased the initial adherence of selected isolates but had
      little effect in overall biofilm formation. CONCLUSIONS: Candida biofilms play a
      role in denture stomatitis.

PMID- 15243472
TI  - An association between oral lichen planus and a persistently dry mouth.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      oral lichen planus and dry mouth by comparing xerostomia scores of individuals
      with oral lichen planus to those of healthy matched controls. STUDY DESIGN:
      Patients who had attended 1 of 2 centers for the management of oral lichen planus
      (n=116), along with age- and sex-matched control subjects (n=348), were sent a
      questionnaire. Nonresponders were invited to complete the questionnaire by
      telephone in lieu of mailing a reply. A standardized medical history was obtained
      for all subjects. RESULTS: The difference between patients with oral lichen
      planus and control subjects for all xerostomia questions was statistically
      significant. In the lichen planus group, the mean xerostomia score was 20.4,
      whereas for control patients, the mean score was 14.7 (P <.001). Stepwise
      conditional logistic regression analysis for the matched case-control groups was
      performed. CONCLUSION: The results demonstrate an association between oral lichen
      planus and xerostomia in some individuals.

PMID- 15243473
TI  - Synchronous occurrence of ipsilateral synovial chondromatosis of the
      temporomandibular joint and pleomorphic adenoma of the parotid gland.
AB  - We present a unique case characterized by true coexistence of synovial
      chondromatosis (SC) of the temporomandibular joint (TMJ) with a salivary gland
      tumor, specifically pleomorphic adenoma, of the ipsilateral parotid gland. The
      possibility that the condition was the result of a single pathologic entity, ie,
      SC with extracapsular involvement or pleomorphic adenoma affecting the TMJ,
      received strong consideration. Nonetheless, careful assessment of the clinical,
      radiographic, MRI, and surgical findings strongly suggested the synchronous
      occurrence of 2 separate pathologic processes, despite their close proximity.
      Further, histopathologic examination confirmed the presence of both SC of the TMJ
      and pleomorphic adenoma of the superficial lobe of the ipsilateral parotid gland.
      Previous reports have pointed out the possibility of misdiagnosing extracapsular
      spread of SC as a salivary gland tumor. Vice versa, it has been noted that
      parotid gland tumors, especially malignant, may cause TMJ symptoms similar to
      those of SC. However, to the best of our knowledge, this is the first time that
      true synchronous occurrence of ipsilateral SC and pleomorphic adenoma, or parotid
      tumor of any kind, is reported.

PMID- 15243474
TI  - Electrolyte concentrations in saliva of children aged 6-10 years with Down
      syndrome.
AB  - STUDY DESIGN: In this study sodium, potassium, calcium, phosphorus, zinc, and
      magnesium ion concentration was analyzed in stimulated whole saliva in 22
      children with Down syndrome aged 6 to 10 years. These children were compared with
      21 healthy children of the same age. Stimulated saliva was collected by chewing a
      piece of parafilm for 10 minutes. The pH was measured with a portable pH meter
      after collection. Electrolyte concentrations were determined by inductively
      coupled argon plasma with atomic emission spectrometry. RESULTS: No statistically
      significant differences were observed in phosphorus, zinc, magnesium, and calcium
      concentration between the children with Down syndrome and the control children.
      The sodium concentration showed about 66.8% higher value in the Down syndrome
      than in the control group. On the other hand the flow rate and potassium
      concentration were lower in the Down syndrome than in the control group.
      CONCLUSION: Our results suggest that there is alteration in the metabolism of the
      duct and/or acinar cells of salivary glands of Down syndrome children.

PMID- 15243475
TI  - Hybrid odontogenic tumor of calcifying odontogenic cyst and ameloblastic fibroma.
AB  - Odontogenic tumors composed of 2 distinct types of lesions are unusual. We report
      an odontogenic tumor that was composed of calcifying odontogenic cyst and
      ameloblastic fibroma that occurred in the right posterior maxilla of a 22-year
      old Korean woman. The tumor had a cystic component with an ameloblastic
      epithelial lining and conglomerates of so-called ghost cells, and there were
      deposits of dentinoid material adjacent to the cyst. These are features
      characteristic of calcifying odontogenic cyst. Enamel organ-like epithelial
      islands were observed within a dental papilla-like stroma of the cyst wall.
      Additionally, a solid portion of the tumor had characteristic features of
      ameloblastic fibroma, i.e., a myxoid cellular stroma with numerous elongated
      islands of ameloblastic epithelium. Ghost cell masses were found in the area of
      ameloblastic fibroma as well. The distribution of the ghost cells suggests that
      this is a hybrid lesion rather than a collision tumor.

PMID- 15243476
TI  - Dentin dysplasia type I: report of atypical cases in the permanent and mixed
      dentitions.
AB  - Dentin dysplasia type I is a rare hereditary disturbance of dentin formation
      characterized clinically by nearly normal appearing crowns and severe
      hypermobility of teeth. Radiographic analysis shows obliteration of all pulp
      chambers, short, blunted, and malformed roots, and periapical radiolucencies of
      noncarious teeth. This paper presents 2 cases demonstrating both classic and
      atypical features of type I dentin dysplasia in the mixed and permanent
      dentitions. The clinical, radiographic, and histopathologic?findings of this
      condition and treatment are described.

PMID- 15243477
TI  - Low prevalence of HPV infection and its natural history in normal oral mucosa
      among volunteers on Miyako Island, Japan.
AB  - OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) infection
      in normal oral mucosa, and to observe the natural history in the oral cavity in
      oral swab samples collected from healthy volunteers on Miyako Island, Okinawa,
      Japan. STUDY DESIGN: The prevalence of HPV infection in oral buccal mucosa cell
      scrapes collected between 2000 and 2002 from a cohort of 668 healthy volunteers
      was determined. HPV DNA was detected by consensus polymerase chain reaction (PCR)
      using MY09/MY11 primers followed by direct cycle sequencing. Just over 2 years
      later the HPV-positive participants were reevaluated. RESULTS: Of the 668
      subjects, 662 samples were analyzed for HPV. HPV DNA was detected in 4 (0.6%)
      specimens. HPV type 16 (HPV16), HPV53, and HPV71, mucosal types, and HPV12, a
      cutaneous type, were all identified by direct sequencing. In the follow-up
      survey, the HPV71- and HPV12-positive participants again tested positive, while
      HPV DNA was not detected in the HPV16- and HPV53-positive participants.
      CONCLUSION: The results of this study among healthy individuals from Miyako
      Island suggest that oral HPV infection is uncommon. In this cohort, HPV71 and
      HPV12 were persistent, while HPV16 and HPV53 were transient in normal oral
      mucosa.

PMID- 15243478
TI  - A preliminary radiographic study of mandibular para-radicular third molar
      radiolucencies.
AB  - OBJECTIVES: To determine the frequency and describe a poorly documented
      radiographically observed variation of normal associated with the roots of
      mandibular third molars--the mandibular third molar para-radicular radiolucency
      (MPR). STUDY DESIGN: A systematic random sample of 822 dental school surgery and
      emergency charts was reviewed for radiographic evidence of the MPR. The frequency
      was determined and the variation in radiographic appearance was described.
      Clinical signs and symptoms were correlated with the presence of an MPR. RESULTS:
      The frequency of the MPR was 7.8% with a female-to-male ratio of 2.6:1.0. Of 6
      bilateral cases (9.4%) all occurred in female patients. The most common location
      was the distal surface of the mandibular third molar. Most (58.6%) were oval in
      shape. CONCLUSION: This radiographic finding most likely represents a variation
      of normal anatomy and based on this retrospective study does not appear to
      require treatment.

PMID- 15243479
TI  - Maxillary bone mineral density and its relationship to the bone mineral density
      of the lumbar spine and hip.
AB  - OBJECTIVE: We sought to measure the bone mineral density (BMD) of various regions
      in the maxilla before implant treatment and to investigate correlations between
      these values and the BMDs of the spine and hip. STUDY DESIGN: Eighteen patients
      were examined by means of quantitative computed tomography, and the BMD of the
      maxillary alveolar ridge was calculated. The same patients also underwent dual
      energy x-ray absorptiometry of the lumbar spine and the total hip. Analysis of
      variance was used to compare BMD values between and within individuals. The
      Pearson correlation coefficient was used to correct for sex and body mass and to
      calculate the correlation between the BMD of the maxillary alveolar ridge and the
      BMD of the spine and hip. RESULTS: The maxillary BMD varied significantly between
      individuals (P <.001) and within individuals (P <.001). The BMD of the anterior
      region of the maxilla was correlated significantly with the BMD of the lumbar
      spine (r=0.6; P <.05). CONCLUSION: A site-specific evaluation of maxillary bone
      tissue could be of value before implant treatment.

PMID- 15243480
TI  - Pseudo bilateral tonsilloliths: a case report and review of the literature.
AB  - Tonsilloliths are very rare concretions found in the tonsillar crypt. They are
      usually single and unilateral, but occasionally may be multiple or bilateral.
      Small concretions in the tonsils are common, but well formed giant unilateral or
      bilateral tonsilloliths are extremely uncommon. Only two cases of bilateral
      tonsilloliths have so far been reported in the literature. A case of unilateral
      tonsillolith, mimicking bilateral tonsilloliths taken with the orthopantogram
      (OPT) in a 57-year-old Malaysian Indian female with squamous cell carcinoma of
      the oral cavity is described. Although the OPT is a reliable and standard
      panoramic X-ray unit used in dentistry, superimposition of a lesion involving one
      side of the jaw creates a pseudo or ghost image on the contralateral side leading
      to a misdiagnosis of bilateral lesions. This report highlights that
      tonsilloliths, though rare, should be considered in the differential diagnosis of
      radiopaque masses involving the mandibular ramus, and that investigations such as
      CT scan or MRI may be required to differentiate pseudo or ghost images from true
      bilateral pathologies.

PMID- 15243481
TI  - A comparison of survival of teeth following endodontic treatment performed by
      general dentists or by specialists.
AB  - OBJECTIVE: A chart review was performed at 3 private general practices in
      different regions of Alabama to compare success of endodontic treatment provided
      by specialists versus generalists. STUDY DESIGN: To qualify for the study the
      general dentists had to perform some endodontic treatment and to refer some to
      endodontists. Success was defined as the treated tooth being present at 5 years
      after the date of treatment initiation. This criterion, was chosen because of its
      unequivocal categorization of results. Calibrated dentists reviewed over 3,000
      charts. RESULTS: 350 met the inclusion criteria. 195 teeth were treated by
      generalists, with an 89.7% success rate. 155 teeth were treated by endodontists,
      with a 98.1% success rate. CONCLUSION: In this limited survey, endodontic
      treatment by specialists was significantly more successful.

PMID- 15243482
TI  - Mycetoma of the maxillary sinus: endodontic and microbiological correlations.
AB  - OBJECTIVE: The purpose was to show the capacity of zinc oxide and eugenol to
      affect the growth of Aspergillus fumigatus. STUDY DESIGN: An in vitro
      microbiological analysis was conducted on samples from infected maxillary sinuses
      and on 3 different endodontic sealers. RESULTS: Tests showed that zinc oxide in
      solution favors the growth of Aspergillus fumigatus, while eugenol inhibits this
      growth, even when mixed with zinc oxide powder. This inhibiting effect decreases
      over time. A reduced effectiveness was demonstrated over a 75-day period.
      CONCLUSIONS: The hypothesis is that the diminishing concentration of eugenol over
      time in endodontic sealers allows the zinc oxide to support growth of Aspergillus
      fumigatus. This is reinforced by clinical experience, where mycetoma has
      developed years after endodontic therapy with excess sealer in the maxillary
      sinus.

PMID- 15243483
TI  - Injection pain and postinjection pain of the anterior middle superior alveolar
      injection administered with the Wand or conventional syringe.
AB  - OBJECTIVE: The purpose of this prospective, randomized, blinded study was to
      compare the pain of injection and post-injection pain of the AMSA injection using
      the computer-assisted Wand Plus injection system versus a conventional syringe.
      STUDY DESIGN: Using a crossover design, 40 subjects randomly received 2 blinded
      AMSA injections using the Wand Plus system and a conventional syringe, at 2
      separate appointments. The AMSA injection site was centered halfway between the
      midpalatine raphe and gingival margin of the first and second premolars. The pain
      of needle insertion, anesthetic solution deposition pain, and postinjection pain
      were recorded on a Heft-Parker VAS for the 2 AMSA injections. RESULTS: For needle
      insertion, 38% of the subjects had moderate/severe pain with the Wand Plus((R))
      and 34% moderate/severe pain with the conventional syringe, with no significant
      difference between techniques. There was a significant difference for solution
      deposition pain, with the conventional syringe causing more moderate/severe pain
      (42% conventional vs. 25% for the Wand Plus. Regarding postinjection pain, after
      numbness wore off there was no significant difference between the Wand Plus
      injection technique (0% moderate pain) and the conventional syringe technique (8%
      moderate pain). Postinjection, approximately 8% to 10% of the subjects
      experienced slight palatal swelling and 2% experienced temporary numbness. These
      problems resolved quickly and were considered minor. CONCLUSIONS: The AMSA
      injection, using the Wand Plus, resulted in similar pain ratings for needle
      insertion as the conventional syringe but statistically lower pain ratings upon
      anesthetic solution deposition. However, the AMSA, using either the Wand Plus or
      a conventional syringe, has the potential to be a painful injection. We found the
      incidence of postinjection pain and sequelae was low with both techniques.

PMID- 15243486
TI  - Measurement of health-related quality of life (HRQOL) associated with skin
      disease.

PMID- 15243487
TI  - White patches and bruised souls: advances in the pathogenesis and treatment of
      vitiligo.

PMID- 15243488
TI  - Fighting and living with vitiligo.

PMID- 15243490
TI  - The "bumps" on my face.

PMID- 15243489
TI  - Hamartomas and tubers from defects in hamartin-tuberin.

PMID- 15243491
TI  - Pseudoxanthoma elasticum 2004.

PMID- 15243492
TI  - PXE: the elephant in my room.

PMID- 15243493
TI  - Alopecia areata: current state of knowledge.

PMID- 15243494
TI  - Ahead with no hair.

PMID- 15243495
TI  - Pemphigus vulgaris--a model for cutaneous autoimmunity.

PMID- 15243496
TI  - Pemphigus: hard to diagnose and treat.

PMID- 15243497
TI  - Atopic dermatitis: broadening the perspective.

PMID- 15243498
TI  - Prison blues.

PMID- 15243499
TI  - Warning: bread may be harmful to your health.

PMID- 15243500
TI  - Extreme itching--a downhill experience.

PMID- 15243501
TI  - Ichthyosiform dermatoses: so many discoveries, so little progress.

PMID- 15243502
TI  - Everything and nothing about ichthyosis.

PMID- 15243503
TI  - An update on the pathogenesis and management of acne vulgaris.

PMID- 15243504
TI  - Acne: a patient's point of view.

PMID- 15243506
TI  - A battle with my skin.

PMID- 15243505
TI  - Innovations in the treatment of psoriasis.

PMID- 15243507
TI  - Cutaneous T-cell lymphoma.

PMID- 15243508
TI  - Clear intention.

PMID- 15243509
TI  - Losing the war on AIDS.

PMID- 15243510
TI  - The more things change, the more they stay inane: living with HIV/AIDS in 2004.

PMID- 15243511
TI  - Hemangiomas: past, present, and future.

PMID- 15243512
TI  - Summer's strawberry.

PMID- 15243513
TI  - Epidermolysis bullosa: then and now.

PMID- 15243514
TI  - A day in the life of a patient with DDEB.

PMID- 15243515
TI  - Contact dermatitis: a quarter century perspective.

PMID- 15243516
TI  - Mystery (misery) resolved.

PMID- 15243517
TI  - Cutaneous melanoma--past, present, and future.

PMID- 15243518
TI  - Surviving melanoma.

PMID- 15243519
TI  - Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar
      elastotic syndromes.
AB  - Elastic fibers in the extracellular matrix are an integral component of dermal
      connective tissue. The resilience and elasticity required for normal structure
      and function of the skin may be attributed to the network of elastic tissue.
      Advances in our understanding of elastic tissue physiology provide a foundation
      for studying the pathogenesis of elastic tissue disorders. Many acquired
      disorders are nevertheless poorly understood due to the paucity of reported
      cases. Several acquired disorders in which accumulation or elastotic degeneration
      of dermal elastic fibers produces prominent clinical and histopathologic features
      have recently been described. They include elastoderma, linear focal elastosis,
      and late-onset focal dermal elastosis and must be differentiated from better
      known disorders, among them acquired pseudoxanthoma elasticum, elastosis
      perforans serpiginosa, and Favre-Racouchot syndrome. Learning objective At the
      conclusion of this learning activity, participants should understand the
      similarities and differences between acquired disorders of elastic tissue that
      are characterized by an increase in elastic tissue, as well as the spectrum of
      solar elastotic dermatoses.

PMID- 15243520
TI  - Comparison of selective retinoic acid receptor- and retinoic X receptor-mediated
      efficacy, tolerance, and survival in cutaneous t-cell lymphoma.
AB  - Primary cutaneous T-cell lymphomas are non-Hodgkin's lymphomas with varied
      clinical presentation and prognosis. The most common subtypes of cutaneous T-cell
      lymphomas are the epidermotropic variants mycosis fungoides and Sezary syndrome.
      Treatment of mycosis fungoides has encompassed a variety of modalities including
      the use of retinoids with several studies evaluating their efficacy. The reported
      benefits and duration of response have varied in published data. The biological
      effect of retinoids is mediated by specific receptor families, retinoic acid
      receptor (RAR) and retinoic X receptor (RXR), with subsequently altered gene
      expression. There are no data available on cutaneous T-cell lymphomas that
      compare RAR and RXR retinoids. The objective of our retrospective, nonrandomized,
      single-center study was to compare the response, survival outcomes, and toxic
      effects in our phase II trial of the RAR-specific retinoid, all-trans retinoic
      acid, with clinical use of the RXR-specific retinoid, bexarotene, in patients
      with mycosis fungoides/Sezary syndrome who have relapsed. There was no
      statistical difference in response rates (12% vs 21%), response duration (20.5 vs
      7.3 months), event-free survival time (4 vs 5 months), or median survival when
      corrected for length of follow-up. Both have favorable toxicity profiles that can
      be managed with medications. The toxicity profile caused by bexarotene seems to
      be more limited to laboratory values and better tolerated, although generally
      associated with more severe grades of toxicity. In conclusion, both retinoids
      have modest objective response rates and, therefore, most likely will have
      limited impact as monotherapeutic agents. However, the immunomodulatory effects
      of RAR and RXR retinoids provide a rational basis for using retinoids in
      combination with other biologic immune response modifiers, phototherapy, or
      cytotoxic chemotherapy.

PMID- 15243521
TI  - An open trial of climatotherapy at the Dead Sea for patch-stage mycosis
      fungoides.
AB  - BACKGROUND: Climatotherapy at the Dead Sea (CDS) is a well-established
      therapeutic modality for moderate to severe psoriasis vulgaris, resulting in
      sustained remissions. It has also been found to be effective for atopic
      dermatitis, another T-cell-mediated dermatosis. OBJECTIVE: We sought to
      prospectively evaluate the efficacy of CDS in patch-stage mycosis fungoides.
      METHODS: A total of 12 patients with patch-stage mycosis fungoides (6 with stage
      IA and 6 with stage IB) were treated with CDS as monotherapy for 28 consecutive
      days according to the protocol for psoriasis, ie, a gradual increase of sun
      exposure to a maximum of 3 hours daily. RESULTS: A total of 9 patients achieved a
      complete clinical response (CCR), defined as no disease activity present; 2
      achieved an almost CCR, defined as the reduction by more than 90% of disease
      activity; and 1 achieved a partial response, ie, reduction by more than 50% of
      disease activity. A CCR was achieved in all the patients with stage IA disease
      and in 3 of the 6 patients with stage IB disease. Of the 9 with a CCR, 6 also
      showed histopathologic clearing. Duration of the remissions, during which no
      therapy was allowed except for emollients, lasted from 2 to 9 months (mean: 5
      months). No serious short-term side effects were recorded. CONCLUSION: CDS
      appears to be an effective, well-tolerated therapy for patch-stage mycosis
      fungoides.

PMID- 15243522
TI  - Granuloma annulare with a mycosis fungoides-like distribution and palisaded
      granulomas of CD68-positive histiocytes.
AB  - We describe 3 unusual cases of granuloma annulare with multiple macular lesions
      in a distribution that simulated mycosis fungoides in patients with no associated
      underlying diseases. Repeated biopsies showed typical well-formed palisading
      granulomas and no evidence of an atypical lymphocytic infiltrate. There was no
      vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients
      had no associated underlying diseases. Most of the histiocytes in the palisading
      granulomas were strongly positive for CD68. The lymphocytes were a minor
      component of the granulomatous inflammation and were predominantly CD8(+) T
      cells. The findings in these cases add to the spectrum of previously defined
      granulomatous eruptions of the skin.

PMID- 15243523
TI  - Ultraviolet exposure is a reinforcing stimulus in frequent indoor tanners.
AB  - BACKGROUND: Investigations into tanners' reasons for tanning have focused
      primarily on the perception of improved appearance. Reported relaxing effects of
      tanning suggest the possibility of a physiologic effect of UV that drives tanning
      behavior. OBJECTIVE: We sought to determine if there is a physiologic reinforcing
      effect of UV exposure, separate from appearance motivation, that may contribute
      to tanning behavior. METHODS: We determined the reinforcing effect of UV light in
      a series of controlled, blinded, repeated-choice trials of UV carefully designed
      to separate as cleanly as possible reinforcing effects of UV exposure from other
      factors including perceived benefits of having a tan. A total of 14 young adults
      who used tanning beds regularly were exposed to otherwise identical UV and non-UV
      tanning bed stimuli on Mondays and Wednesdays for 6 weeks. On Fridays,
      participants had concurrent access to the two beds. The primary dependent
      variable was the percentage of choice sessions during which more UV than non-UV
      tanning was chosen. RESULTS: In all, 12 participants chose additional tanning
      exposure on Fridays and, of these, 11 consistently used the UV bed for that
      exposure. Of the total 41 occasions when participants chose to tan on Friday, 39
      sessions (95%) were for the UV bed and only two for the non-UV bed. A more
      relaxed and less tense mood was reported after UV exposure compared with after
      non-UV exposure (P=.008 and P=.002, respectively). DISCUSSION: When exposed to UV
      and non-UV under blinded conditions, frequent tanners can distinguish the two
      conditions and undertake further UV exposure, indicating that UV is a reinforcing
      stimulus. The relaxing and reinforcing effects of UV exposure contribute to
      tanning behavior in frequent tanners and should be explored in greater detail.

PMID- 15243524
TI  - Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger
      RNA expression of proinflammatory cytokines.
AB  - BACKGROUND: Previous studies have documented humoral and cell-mediated
      immunologic defects in patients with vitiligo. OBJECTIVE: This 24-week study
      assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with
      generalized vitiligo as well as the pretreatment and post-treatment expression of
      cytokines in the depigmented and normal skin of patients compared with controls.
      METHODS: Twenty-three patients were enrolled in this investigation, and 19
      patients completed the study; 8 were male and 11 were female. Fifteen age-, race
      , and sex-matched control subjects were also included. Patients were treated with
      tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed
      at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were
      taken from the depigmented, non-sun-exposed skin and adjacent normal skin of
      patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of
      controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL
      10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were
      determined by real-time quantitative polymerase chain reaction. RESULTS: At 24
      weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There
      was a statistically significant decrease in overall disease severity scores at 24
      weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or
      neck lesions. Signs and symptoms of irritation were minimal. At baseline,
      compared with healthy controls, vitiligo patients demonstrated a statistically
      significant increase in the expression of IFN-gamma in involved and adjacent
      uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF
      alpha expression in involved and uninvolved skin (P=.01 and P=0.02,
      respectively); and significantly increased IL-10 expression in involved and
      uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha
      expression decreased in the depigmented and adjacent uninvolved skin (P <.001).
      There was no statistically significant change in IL-10 or IFN-gamma
      posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and
      effective therapy for patients with vitiligo. It further suggests that an
      imbalance in local cytokine expression may play a role in the pathogenesis of
      vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be
      associated with repigmentation of vitiligo.

PMID- 15243525
TI  - Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies.
AB  - BACKGROUND: Anti-desmoplakin (DP) antibodies are present in paraneoplastic
      pemphigus (PNP) as a component of a complex humoral autoimmune reaction
      characterized by antibodies against proteins of the plakin family, desmogleins,
      and an unidentified 170 kd protein. Anti-DP antibodies have also been rarely
      identified in other blistering diseases. The significance of anti-DP antibodies
      in the pathogenesis of bullous diseases is unclear. OBSERVATION: We studied 3
      patients with severe and chronic mucosal dominant pemphigus vulgaris (PV). In
      addition to anti-desmoglein 3 antibodies, these patients had anti-DP
      autoantibodies, demonstrable by immunofluorescence (IF), immunoprecipitation
      (IP), and indirect immunoelectromicroscopy (IIEM). This finding suggested these
      patients may have had PNP and not PV. However, antibodies against periplakin,
      envoplakin, bullous pemphigoid antigen 1 (BPAG 1), plectin, and 170 kd PNP
      antigen could not be detected using IP and immunoblotting. Extensive and repeated
      investigations for an underlying neoplasm throughout the follow-up period were
      consistently negative for all patients. CONCLUSION: This study demonstrates that
      anti-DP antibodies without the presence of any other anti-plakin antibodies are
      not specific for PNP, and are present in some cases of PV. Cellular disadhesion
      induced by anti-desmoglein antibodies can trigger an epitope-spreading phenomenon
      with a secondary formation of autoantibodies against desmoplakins, intracellular
      desmosomal antigens. The role of anti-DP antibodies in the pathogenesis of these
      PV patients is still unclear. The presence of anti-DP antibodies will produce a
      false positive serologic interpretation for the diagnosis of PNP especially if
      one uses only indirect IF on murine bladder, the most commonly employed screening
      test to identify PNP. More specific immunologic tests are required in this subset
      of patients with PV.

PMID- 15243526
TI  - Treatment of vitiligo by transplantation of cultured pure melanocyte suspension:
      analysis of 120 cases.
AB  - BACKGROUND: Despite the availability of various medical treatments for vitiligo,
      a large percentage of patients fail to achieve satisfactory results. Surgical
      techniques offer a potential solution for patients with vitiligo who fail to
      respond to medical treatments. OBJECTIVE: We evaluated the practicality in
      treating vitiligo by using cultured autologous pure melanocytes and investigated
      the different results among stable localized vitiligo, stable generalized
      vitiligo, and active generalized vitiligo. METHODS: In all, 120 patients with
      vitiligo were treated with transplantation of autologous cultured pure melanocyte
      suspension after carbon-dioxide laser abrasion. RESULTS: Patients with stable
      localized vitiligo experienced the highest percentage of excellent repigmentation
      with 84% achieving 90% to 100% coverage, followed by 54% of patients with stable
      generalized vitiligo, whereas only 14% of patients with active generalized
      vitiligo experienced good repigmentation. Age and sex of the patients, and size
      and location of the lesions, did not show significant influence on the results of
      transplantation. CONCLUSION: Autologous cultured pure melanocyte suspension
      combined with carbon-dioxide laser abrasion is an effective treatment for
      patients with stable vitiligo who fail to respond to medical treatments,
      especially for those with stable localized vitiligo.

PMID- 15243527
TI  - Eruptive linear papules on the abdomen of a woman with ascites.

PMID- 15243528
TI  - How to reply to referees' comments when submitting manuscripts for publication.
AB  - BACKGROUND: The publication of articles in peer-reviewed scientific journals is a
      fairly complex and step-wise process that involves responding to referees'
      comments. Little guidance is available in the biomedical literature on how to
      deal with such comments. OBJECTIVE: The objective of this article is to provide
      guidance to novice writers on dealing with peer review comments in a way that
      maximizes the chance of subsequent acceptance. METHODS: This will be a literature
      review and review of the author's experience as a writer and referee. RESULTS:
      Where possible, the author should consider revising and resubmitting rather than
      sending an article elsewhere. A structured layout for responding to referees'
      comments is suggested that includes the 3 golden rules: (1) respond completely;
      (2) respond politely; and (3) respond with evidence. CONCLUSION: Responding to
      referees' comments requires the writer to overcome any feelings of personal
      attack, and to instead concentrate on addressing referees' concerns in a
      courteous, objective, and evidence-based way.

PMID- 15243530
TI  - Rosacea subtype-directed therapy.
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely dermatologic
      topics. Commentaries from the Dialogues Editor-in-Chief, Warren R. Heymann, MD,
      are provided after each discussion as a topic summary. These highlights are
      provided as a special service to JAAD readers.

PMID- 15243529
TI  - Helen Ollendorff Curth and William Curth: from Breslau and Berlin to Bar Harbor.

PMID- 15243531
TI  - Surgical pearl: earlobe repair assisted by guidewire punch technique: a useful
      method to remove unwanted epithelial tracts caused by body piercing.

PMID- 15243532
TI  - Localized linear IgA disease induced by ampicillin/sulbactam.
AB  - We describe a patient who developed an exclusively perianal-intergluteal
      vesicular eruption after receiving a course of ampicillin/sulbactam. Direct
      immunofluorescence microscopy of perilesional skin demonstrated linear deposits
      of IgA along the dermal-epidermal junction. Circulating IgA autoantibodies
      against the 120-kd soluble ectodomain of bullous pemphigoid antigen 180 (LAD-1
      autoantigen) were detected by immunoblotting. Discontinuation of the antibiotics
      resulted in a rapid resolution of the skin lesions. This is a most unusual case
      of localized drug-induced linear IgA disease.

PMID- 15243533
TI  - Cutaneous findings in patients with pulmonary arterial hypertension receiving
      long-term epoprostenol therapy.
AB  - Pulmonary arterial hypertension (PAH) is a rare debilitating disease
      characterized by an increase in pulmonary vascular resistance and progressive
      right ventricular failure. PAH may be primary or associated with other conditions
      such as collagen vascular disease, portal hypertension, and HIV. Intravenous
      epoprostenol improves the survival, exercise tolerance, hemodynamics, and quality
      of life in patients with PAH and is believed to work through multiple pathways
      including vasodilation, opposition of smooth-muscle hypertrophy, and inhibition
      of platelet aggregation. Common dose-limiting side effects are flushing, jaw
      pain, arthralgias, myalgias, and headache, which are attributed to the
      vasodilatory effects of epoprostenol. In clinical practice, patients often
      develop persistent rash that is distinct from the flushing associated with
      epoprostenol. The specific findings both on physical examination and on
      dermatopathology have not, however, been well described. This report describes
      the cutaneous and dermatopathologic findings of 12 patients who developed
      persistent rash while receiving long-term prostacyclin for PAH.

PMID- 15243534
TI  - Management of multifocal primary cutaneous CD30 anaplastic large cell lymphoma.
AB  - Primary cutaneous CD30(+) anaplastic large cell lymphoma in adults is rare, but
      the prognosis is generally excellent. Skin lesions may be localized or, less
      commonly, multifocal. Although not extensively reported, multifocal primary
      cutaneous anaplastic large cell lymphoma tends to relapse after systemic
      chemotherapy and is generally considered more prone to progress to extracutaneous
      involvement than the localized disease. We report the case of a 21-year-old woman
      with primary cutaneous CD30(+) anaplastic large cell lymphoma manifesting as
      widespread papules and nodules. Despite remaining localized to the skin, the
      disease relapsed after multiple chemotherapy regimens and autologous stem-cell
      transplantation. Treatment with an experimental anti-CD30 monoclonal antibody was
      successful. Review of this case and similar cases illustrates that traditional
      combination chemotherapy may not be best. Newer treatments, including anti-CD30
      monoclonal antibodies, show promise. However, further study is needed to develop
      optimal therapeutic strategies.

PMID- 15243535
TI  - Clonal identity between skin and synovial tissue in a case of mycosis fungoides
      with polyarthritis.
AB  - Polyarthritis in the presence of a cutaneous T-cell lymphoma is a rare
      phenomenon. We describe a case of mycosis fungoides with development of a
      symmetric erosive polyarthritis of the small hand joints and feet, diagnosed as
      rheumatoid arthritis. An identical monoclonal T-cell population in the skin and
      in the synovium was detected by T-cell receptor gene rearrangement analysis,
      illustrating articular dissemination of lymphoma cells. Differentiating mycosis
      fungoides-associated arthritis from rheumatoid arthritis may have important
      implications for treatment. Based on this case, the relevant literature, and the
      newest disease concepts, pathogenic mechanisms and therapeutic options of mycosis
      fungoides-associated arthritis are discussed.

PMID- 15243536
TI  - A patient with both bullous pemphigoid and epidermolysis bullosa acquisita: an
      example of intermolecular epitope spreading.
AB  - Bullous pemphigoid (BP) and epidermolysis bullosa acquisita are distinct
      autoimmune blistering disorders. BP is characterized by autoantibodies directed
      against the NC16A domain of collagen XVII, whereas patients with epidermolysis
      bullosa acquisita have autoantibodies against the NC1 domain of type VII
      collagen. We followed up a patient with BP for 9 years. During that time his
      clinical disease took on several features suggestive of epidermolysis bullosa
      acquisita. The objective of this study was to determine if the patient's
      autoantibody profile reflected the change in his clinical picture. Enzyme-linked
      immunosorbent assay and immunoblotting for detection and subclass determination
      of autoantibodies to type XVII and type VII collagen were performed on banked
      patient sera from the 9-year period. The patient's initial autoantibodies were
      exclusively IgG1 directed against collagen XVII. During the course of his
      illness, the subclass specificity of the patient's type XVII collagen
      autoantibodies shifted to the IgG4 subclass and during the same time interval the
      patient developed IgG2 autoantibodies directed against type VII collagen. This
      patient with BP exhibited both subclass shifting and development of a second
      autoantibody system that correlated with a change in the clinical appearance of
      the disease. The analysis of the patient's autoantibodies provides strong
      evidence for the involvement of epitope spreading in the evolution of his
      autoimmune disease.

PMID- 15243537
TI  - Cutaneous T-cell lymphoma sparing resolving dermatomal herpes zoster lesions: an
      unusual phenomenon and implications for pathophysiology.
AB  - Exclusion of cutaneous T-cell lymphoma (CTCL) by another dermatosis has not been
      reported. The mechanism for the epidermotropism of helper T lymphocytes in this
      indolent malignancy is not known. Although there is evidence that Langerhans
      cells (LC) play a role in the epidermotropism of lymphocytes in CTCL, clinical or
      in vivo support is lacking. We describe a patient with CTCL who developed herpes
      zoster involving the left T8 dermatome. When his CTCL became widespread after the
      herpes zoster healed, the previously affected areas of herpes zoster and their
      periphery were clinically free of lymphoma. Immunohistochemical analysis of a
      clinically uninvolved patch revealed absence of CD1a(+) cells in the epidermis,
      consistent with loss of LC in the areas spared by CTCL. There was no loss of LC
      in areas affected by CTCL. This is an unusual inhibition of CTCL by a prior viral
      infection. The loss of LC in the clinically spared skin suggests a role for LC in
      the epidermotropism of lymphocytes in CTCL.

PMID- 15243538
TI  - Treatment of recalcitrant scleromyxedema with thalidomide in 3 patients.
AB  - Scleromyxedema is a generalized, papular, and sclerodermoid form of lichen
      myxedematosus associated with monoclonal gammopathy and systemic changes. Despite
      anecdotal reports of success with various agents, no satisfactory treatments are
      currently available. We report 3 adult patients with recalcitrant scleromyxedema
      associated with paraproteinemia who were treated with thalidomide. All 3 patients
      had marked improvement of the skin lesions and joint mobility after the first 2
      months of therapy, with further amelioration after 4 months, and reduction in
      paraprotein levels.

PMID- 15243539
TI  - Management of cutaneous lesions associated with an emerging epidemic: community
      acquired methicillin-resistant Staphylococcus aureus skin infections.

PMID- 15243540
TI  - A vesiculopustular variant of mycosis fungoides palmaris et plantaris
      masquerading as palmoplantar pustulosis with nail involvement.

PMID- 15243541
TI  - Enoxaparin sodium-induced bullous pemphigoid-like eruption: a report of 2 cases.

PMID- 15243542
TI  - Death from cerebrovascular infarction in a patient with PHACES syndrome.

PMID- 15243543
TI  - Metastatic transitional cell carcinoma of the bladder presenting as genital
      edema.

PMID- 15243544
TI  - Primary follicular mucinosis and association with mycosis fungoides and other
      cutaneous T-cell lymphomas.

PMID- 15243545
TI  - Psoriasis and vitiligo.

PMID- 15243546
TI  - Look out, dermatology: here comes Wal-Mart.

PMID- 15243548
TI  - The vitamin D dilemma.

PMID- 15243549
TI  - Special report: reassessment of the ORL-HNS workforce: perceptions and realities.
AB  - OBJECTIVE: This Workforce Study re-examined the current scope and geographic
      distribution of Otolaryngology practice and assessed the otolaryngologists' role
      in relation to other specialists in the diagnosis and treatment of disorders of
      the ear, nose, throat, and related structures of the head and neck. Study design
      A national survey and review of federal, corporate and administrative databases,
      coupled wih a focus group of otolaryngologists, were analyzed to compile
      physician manpower figures, state and regional demographic data, and prediction
      modeling of Managed Care and FFS environments. RESULTS: The current and predicted
      workforce supply and demographic data support a geographic and proportionate
      increase in the number of otolaryngologists practicing and entering the
      workforce. Additional findings involving the role of the specialty specifically
      identified an increase in the treatment of allergic disease within the Managed
      Care sector and a diminution of the gatekeeper concept. Demographic findings
      represent a stable age distribution of 40 to 49 and 50 to 59 year old
      otolaryngologists, with a noted increase in the number of women entering the
      field. Empiric data reflects the continuous, diverse and dominant role
      otolaryngologists maintain in the treatment and care of patients with
      otolaryngologic and head and neck disease. CONCLUSIONS: This study continues the
      effort to identify otolaryngology workforce demographic profiles and make
      recommendations for a future national practice model. Continuous reassessment of
      the specialty is required.

PMID- 15243550
TI  - Endoscopic treatment of laryngeal and tracheal stenosis-has mitomycin C improved
      the outcome?
AB  - OBJECTIVE: The management of laryngeal and tracheal stenosis remains a
      challenging problem despite advances in endoscopic surgical techniques. Scar
      formation and restenosis is the main cause of failure, and this study assesses
      the efficacy of two adjuvant treatments: endoscopic steroid injection and topical
      mitomycin C application. Study design and setting This is a retrospective cohort
      study comparing the efficacy of 3 endoscopic techniques: (1) carbon dioxide
      (CO(2)) laser incisions with bronchoscopic dilatation, (2) CO(2) laser with
      dilatation followed by steroid injection into the stenotic area, and (3) CO(2)
      laser with dilatation followed by topical application of mitomycin C. Included in
      the statistical analysis were 47 procedures performed by the senior investigator
      in a tertiary medical center between 1994 and 2001 based on their success or
      failure. RESULTS: The percentages of successful outcomes in the study groups were
      15%, 18.2%, and 75% with the CO(2) laser, CO(2) laser with steroid injection, and
      CO(2) laser with mitomycin C, respectively. Statistical comparisons reveal that
      the differences in outcomes were statistically significant (P < 0.05) between the
      mitomycin group and each of the other two treatment groups, whereas there was no
      statistically significant difference between the laser only and laser with
      steroid groups. There were no complications noted with the use of adjuvant
      medications. CONCLUSION: These patient group results indicate a statistically
      significant increase, from <20% to 75%, in the success rate of endoscopic
      treatment of acquired upper airway stenosis when topical mitomycin C is added to
      the treatment regimen. No benefit has been demonstrated for using intraoperative
      local steroid injections as an adjunct to laser treatment. Clinical significance
      Mitomycin C appears to be an effective and safe adjuvant treatment in the
      endoscopic management of laryngeal and tracheal stenosis.

PMID- 15243552
TI  - Pediatric suprastomal granuloma: management and treatment.
AB  - OBJECTIVE: Suprastomal granulomas (SSG) are a common complication of pediatric
      tracheotomy. Occasionally excision is indicated for obstructive granulomas. We
      report on our experience on the management of SSG requiring excision. Study
      design and setting A retrospective chart review of 68 patients who underwent SSG
      excision at a tertiary referral pediatric hospital between July 1997 and November
      2002. The medical charts were reviewed for excision techniques and outcomes.
      RESULTS: A total of 106 excisions of SSG were performed on 68 patients. Of the
      patients, 25 (36.8%) required multiple excisions. Removal techniques included
      sphenoid punch (34.9%), optical forceps (34.0%), open excision (22.6%),
      electrocautery (4.7%), and hook and eversion (3.8%). CONCLUSION: The majority of
      SSG do not require removal. If excision is indicated, we recommend using optical
      forceps for soft and friable lesions and the sphenoid punch for fibrous and firm
      granulomas. For granulomas that have a broad base, are very large, or where
      endoscopic instrumentation is not possible, we recommend open excision.

PMID- 15243553
TI  - Wireless pH testing as an adjunct to unsedated transnasal esophagoscopy: the
      safety and efficacy of transnasal telemetry capsule placement.
AB  - OBJECTIVES: The introduction of 48-hour wireless pH testing offers clinicians a
      new alternative for the objective documentation of reflux. The success of
      transnasal wireless pH capsule placement has not been previously described. The
      purpose of this investigation was to describe our experience with transnasal
      wireless pH capsule placement. METHODOLOGY: All patients undergoing unsedated
      transnasal esophagoscopy and wireless pH capsule placement between January 1,
      2003 and July 31, 2003 were prospectively evaluated. Data concerning patient
      tolerance, success of capsule placement and function, complications, and pH
      recordings were collected. RESULTS: During this time, 46 persons were evaluated.
      The mean age of the cohort was 52 years. Of the patients, 50% were male. The
      indications for the procedure were chronic cough (18/46), gastroesophageal reflux
      disease (18/46), and larygopharyngeal reflux (10). Of the procedures performed,
      85% (39/46) were successful. Complications included epistaxis (2/46),
      laryngospasm (2/46), and vasovagal reaction (1/46). CONCLUSIONS: The transnasal
      placement of a wireless pH capsule is a safe and effective diagnostic adjunct to
      unsedated transnasal esophagoscopy.

PMID- 15243554
TI  - Prevalence of extraesophageal reflux in patients with symptoms of
      gastroesophageal reflux.
AB  - OBJECTIVES: To compare the prevalence of extraesophageal reflux (EER) in patients
      with heartburn, posterior laryngitis (PL), and in healthy controls. Study design
      and setting A retrospective and prospective study including a total of 101
      subjects who underwent 24-hour dual-probe pH monitoring. RESULTS: 52% of the
      subjects with heartburn had EER. No significant differences were found between
      the PL and heartburn groups for any pharyngeal reflux parameters. However, supine
      pharyngeal reflux was significantly more prevalent in heartburn patients with
      GERD than in PL patients and healthy controls (P < 0.05). Significant positive
      correlation (P < 0.01) was found between the percentage of time pH <4 in the
      pharynx and in the distal esophagus. CONCLUSION: EER occurs in the majority of
      heartburn patients who are lacking laryngeal symptoms. Abnormal distal esophageal
      acid exposure makes the occurrence of EER more likely. SIGNIFICANCE: EER appears
      to be a continuum without clear-cut differences between the groups.

PMID- 15243555
TI  - Intracordal injection of autologous auricular cartilage in the paralyzed canine
      vocal fold.
AB  - OBJECTIVE: Vocal fold augmentation by injectable material under direct visual
      control is an easy and simple operation. However, when autologous fat or bovine
      collagen is used, resorption creates a problem. And autologous fascia is debating
      about absorption now days. This study is to evaluate the histology of minced and
      injected autologous auricular cartilage and fat graft in the augmentation of
      unilateral vocal fold paralysis using a canine model. METHOD: Nine dogs were
      operated. At first, a piece of auricular cartilage was harvested from ear and
      minced into tiny chips with a scalpel, and a piece of fat tissue was harvested
      from inguinal area and minced into tiny chips with a scalpel. Cutting off a
      section of the recurrent nerve paralyzed the right vocal fold. The minced
      cartilage and fat-paste (0.2 mL) was injected using a pressure syringe into the
      paralyzed thyroarytenoid muscle under direct laryngoscopy. Two animals were
      sacrificed at 3 days, three at 3 weeks, two at 3 months, one at 6 months, and one
      at 12 months. Each dog underwent laryngectomy and serial coronal sections of
      paraffin blocks from the posterior part of the vocal fold were made. RESULTS:
      There was no significant complication perioperatively and during follow-up. There
      was acute inflammatory findings in the graft at 3 days and 3 weeks. The injected
      cartilage remained in the larynx until 12 months. CONCLUSION: The autologous
      auricular cartilage graft is well tolerated and may be very effective material
      for volumetric augmentation on paralyzed vocal cord.

PMID- 15243556
TI  - Preliminary report of endolaryngeal and endotracheal laser surgery of juvenile
      onset recurrent respiratory papillomatosis by Nd:YAG laser and a new fiber
      guidance instrument.
AB  - OBJECTIVES: Recurrent respiratory papillomatosis (RRP) caused by human papilloma
      virus (type 6 and 11) is the most common benign neoplasm of the larynx in
      children. Despite being a benign disease, treatment is very difficult and is
      characterized by frequent recurrence, spread throughout the respiratory tract,
      and malignant degeneration. Besides surgical resection and the established CO(2)
      laser treatment, laser surgery by fiber-guided Nd:YAG laser light promises to be
      a bloodless and effective treatment procedure. To improve this new method, a
      novel fiber guidance instrument has been developed to aid in endolaryngal laser
      surgery of RRP. Study design and setting The method described uses a specially
      designed instrument for fiber guidance that is equipped with a bendable distal
      tip to move the fiber end precisely. Moreover, the instrument includes an
      additional channel for the suction of smoke and pyrolysis products. Up to now, 5
      patients (aged 4 to 8 years) with RRP were treated by Nd:YAG laser light (lambda
      = 1064 nm; power, 10 W; irradiance, 3.5 kW/cm(2), continuous wave) with a
      prototype version of the new instrument and were followed up for 12 months each.
      RESULTS: Because of the adequate length and the bendable distal tip with a range
      of -5 degrees up to 45 degrees to the optical axis of the fiber and less than 10%
      light loss at maximal deflection, RRP can be treated by Nd:YAG laser light easily
      and precisely. The continuous suctioning ensured an optimum view of the operating
      field and a minimal load of potential infectious laser plume and toxic pyrolysis
      products for the patient as well as for the physician. The laser treatment of RRP
      with the new fiber guidance instrument was only minimally traumatic. During 1
      year follow-up visits, all Nd:YAG laser light-treated patients, showed a
      regression of the disease. CONCLUSIONS: The new fiber guidance instrument enables
      a precise and easy treatment of the RRP with fiber-guided laser systems (eg,
      Nd:YAG-, diode-, and KTP-lasers) and an effective removal of infectious laser
      plume as well as toxic pyrolysis products. A follow-up period of 1 year revealed
      that Nd:YAG laser surgery seems to prevent a rapid recurrence of juvenile
      respiratory papillomatosis in the treated patients.

PMID- 15243557
TI  - Removal of fish bones in the oropharynx and hypopharynx under video laryngeal
      telescopic guidance.
AB  - OBJECTIVE: The study goal was to present the technique and results of removal of
      fish bones in the oropharynx and hypopharynx under video laryngeal telescopic
      guidance. Study design and set From January 2001 to December 2002, a total of 27
      patients with fish bones lodged in the oropharynx and hypopharynx were studied at
      the ENT Department of Taipei Medical University Hospital. RESULTS: All fish bones
      were removed smoothly without necessitating further procedures at the time of the
      initial clinical examination and had an uneventful clinical course. CONCLUSION:
      Removal of fish bones lodged at the tongue base, vallecula, and hypopharynx under
      video laryngeal telescopic guidance has the advantages of good illumination,
      clear visualization, and precise extraction.The technique has also proven to be
      efficient, safe, well tolerated, and with low morbidity. SIGNIFICANCE: Removal of
      the fish bones from difficult areas in oropharynx and hypopharynx with this
      technique can reduce the use of direct laryngoscope under general anesthesia.

PMID- 15243558
TI  - Fusaric acid: a novel agent and mechanism to treat HNSCC.
AB  - OBJECTIVE: A new class of carboxylic acids has tumoricidal activity for head and
      neck squamous cell cancer (HNSCC). Fusaric acid (FA) can chelate divalent
      cations, especially zinc, and inactivate zinc finger proteins involved in DNA
      repair and protein synthesis. METHODS: 2 squamous carcinoma lines were utilized
      for in vitro and in vivo portions of this study. Cell counting and flow cytometry
      were used to analyze cells in culture in treatment and control groups over 96
      hours. HNSCC subcutaneous implants were created in treatment and control groups
      of BALB-c nude mice (N = 30). RESULTS: In vitro studies demonstrated significant
      changes in cell numbers and cell cycle. In vivo studies of daily intralesional
      therapy for 1 month also showed reduced onset of growth and overall growth
      compared to controls. CONCLUSION: FA appears to have a tumoristatic/tumoricidal
      effect on HNSCC. Further nude mice studies are needed to optimize dosing and
      administration regimens for FA in anticipation of clinical trials.

PMID- 15243559
TI  - Predictors of wound complications after laryngectomy: A study of over 2000
      patients.
AB  - OBJECTIVES: To identify risk factors for and the rate of wound complications
      after laryngectomy in a large, prospectively collected national dataset, and to
      generate a predictive model. Study design We used the National Surgical Quality
      Improvement Program (NSQIP) registry created by the Department of Veterans
      Affairs (VA) to identify patients undergoing total laryngectomy from 1989 to 1999
      (n = 2063). We linked these data to inpatient and outpatient VA administrative
      records to capture data for prior radiation. Over 20 preoperative and
      intraoperative risk factors were analyzed using bivariate techniques. Those
      significant at the P < 0.01 level were analyzed with logistic regression and
      conjunctive consolidation to identify independent predictors of wound
      complications. RESULTS: The overall wound complication rate was 10.0%. In
      adjusted analyses, prolonged operative time (>10 hours, odds ratio = 2.10, 95%
      confidence interval: 1.32-3.36), exposure to prior radiation therapy (OR =1.63,
      1.07-2.46), presence of diabetes (OR =1.78, 1.04-3.04), preoperative
      hypoalbuminemia (OR =1.90, 1.32-2.74), anemia (OR =1.59, 1.07-2.36), and
      thrombocytosis (OR =1.48, 1.04-2.10) were independently associated with
      postoperative wound complications. A prognostic model using three variables-prior
      radiation therapy, diabetes, and hypoalbuminemia-provided excellent risk
      stratification into three tiers (6.3%, 13.7%, 21.7%). CONCLUSIONS: Preoperative
      radiation, prolonged operative time, low albumin, and diabetes were independently
      associated with postoperative wound infections. These results will help to
      identify patients at risk for wound complications, thus allowing for heightened
      surveillance and preventive measures where possible.

PMID- 15243560
TI  - Extended pericranial flap and bone graft reconstruction in anterior skull base
      surgery.
AB  - OBJECTIVES: The objectives of this study was to establish a rationale for
      repairing large anterior skull base defects with an extended pericranial flap and
      split calvarial bone graft; to define large anterior skull base defects as those
      spanning the anterior cranial measuring at least 3.0 x 4.0 cm; and to describe
      the surgical technique and compare it with alternative strategies. Study design
      Thirty-four patients underwent anterior craniofacial resection of anterior skull
      based tumors of varying histology with reconstruction using an extended
      pericranial flap and split calvarial bone graft. RESULTS: The survival of the
      pericranial flap and bone graft was maintained in 33 of 34 patients. There was 1
      episode of postoperative cerebrospinal fluid leak, 1 episode of osteomyelitis of
      the bone graft and an epidural abscess, and 1 episode of asymptomatic
      pneumocephalus. CONCLUSION: Split calvarial bone graft with an extended
      pericranial flap is an effective technique for reconstructing large anterior
      skull base defects.

PMID- 15243561
TI  - c-myc and bcl-2 Expression in supraglottic squamous cell carcinoma of the larynx.
AB  - OBJECTIVES: To evaluate the expression and prognostic significance of c-myc and
      bcl-2 oncogenes in squamous cell carcinoma (SCC) of the supraglottic larynx.
      Study design A retrospective cohort study of 61 patients who underwent surgery
      for SCC of the supraglottic larynx. Gender, age, TNM status, operative procedure,
      recurrences, and disease-free survival periods were recorded. METHODS:
      Hematoxylin and eosin-stained sections were reexamined for grade, invasion of
      tumor margins, lymphovascular invasion, lymphocyte infiltration, and perineural
      invasion. Immunohistochemical detection of c-myc and bcl-2 oncogenes was
      performed using monoclonal antibodies. RESULTS: No correlation was observed
      between either c-myc or bcl-2 and the clinical and histopathologic parameters.
      Survival analysis revealed no correlation of either c-myc (P = 0.88) or bcl-2 (P
      = 0.85) with the disease-free survival. c-myc expression was found to be
      significantly higher in bcl-2-positive patients (P = 0.001). CONCLUSION: Neither
      c-myc nor bcl-2 had shown to be prognostic factor for laryngeal carcinoma in this
      present study. Correlation between c-myc and bcl-2 supports the experimental
      observations of cooperative action between these two genes in tumorigenesis.

PMID- 15243562
TI  - Expression of mucin gene products in laryngeal squamous cancer.
AB  - OBJECTIVE: Mucins are high-molecular-weight glycoproteins present at the outer
      surface of mammalian cells. The objective of this study was to examine the
      expression of mucin (MUC) genes 3, 4, 5AC, 5B, 6, and 7 in early and late
      laryngeal squamous cancer using the in situ hybridization technique. Study design
      Retrospective analysis of pathological archive specimens. RESULTS: While MUC 3
      and 7 are expressed in a small proportion of early cancers, MUC 5AC, 5B, and 6
      are not expressed in laryngeal squamous cancer. MUC 4 was expressed in 13 of the
      30 patients. Ten patients and 3 patients with stage 1 and stage 4 disease
      respectively expressed MUC 4 gene (Fisher's exact, P = 0.02). MUC 4-positive
      patients had a definite trend towards better survival (log rank test, P = 0.05).
      In the presence of tumor stage and comorbidity grade, Cox's proportional hazards
      model failed to statistically confirm the survival advantage provided by MUC 4
      gene expression. CONCLUSION: There is a survival advantage for patients with
      advanced-stage nonmetastatic cancer when the MUC 4 gene is expressed. AIMS: To
      study the expression of mucin (MUC) genes 3, 4, 5AC, 5B, 6, and 7 in early and
      advanced squamous cell cancer of the larynx; to attempt to correlate changes in
      gene expression with tumor stage by studying stage I and stage IV (AJCC, 1988)
      tumors.

PMID- 15243563
TI  - Z-palatoplasty (ZPP): a technique for patients without tonsils.
AB  - OBJECTIVE: Patients without tonsils and with Friedman tongue position (FTP) III
      and IV are poor candidates for uvulopalatopharyngoplasty (UP3). Even when
      combined with adjunctive hyopharyngeal techniques, results are poor. We assessed
      a modified uvulopalatoplasty based on a bilateral Z-plasty in treating patients
      without tonsils who have obstructive sleep apnea/hypopnea syndrome (OSAHS).
      METHODS: 25 patients treated with a modified technique were matched with 25
      patients previously treated with classic UP3. All patients in both groups also
      had radiofrequency tongue base reduction. Preoperative vs. postoperative measures
      of objective treatment success and subjective symptoms were compared for the 2
      groups. Morbidity, including pain levels, narcotic use, and return to solid diet
      and normal activity, as well as complications were studied. RESULTS: Subjective
      improvement was good for both groups, but objective clinical improvement was
      significantly better for the experimental group. Morbidity and complications for
      the experimental group were comparable to the control group and to other
      published series on UP3. CONCLUSIONS: A modified technique for patients without
      tonsils who have OSAHS is presented. The new technique is more successful with
      acceptable morbidity for patients with OSAHS than classical techniques.

PMID- 15243564
TI  - Significance of asymptomatic tonsil asymmetry.
AB  - OBJECTIVE: Asymmetry of tonsils that arouses suspicion for malignancy is one of
      the indications for tonsillectomy. The purpose of this study was to evaluate the
      incidence of occult malignancy in patients with asymptomatic unilateral tonsillar
      enlargement. Study design and setting A prospective controlled trial was carried
      out in two institutions, Beyoglu Research and Training Hospital and Karaelmas
      University Hospital, during a 6-year period. Of patients selected for
      tonsillectomy, patients with unilateral tonsillar enlargement were identified and
      were included in this study. Patients who had risk factors that were significant
      for malignancy were excluded. After excision, two tonsil specimens were measured
      before sending for histology. Matched controls with symmetric tonsils underwent
      the same procedures. Preoperative diagnosis of tonsil asymmetry with the
      postoperative histologic diagnosis were correlated for the incidence of
      malignancy. RESULTS: Of the 792 patients undergoing tonsillectomy, 53 patients
      (6.69%) with asymmetry of tonsils and who had no other risk factors for
      malignancy underwent tonsillectomy. The size difference of the tonsils ranged
      from 0 to 19 mm. In the control group of 51 patients with symmetric tonsils, the
      size difference ranged from 0 to 8 mm. The analysis showed statistically
      significant difference in the degree of asymmetry between the two groups (P
      <.001). Most of the specimens contained reactive lymphoid hyperplasia in both
      groups (58.49% and 54.9%, respectively). No malignancies or unusual pathological
      findings were encountered on histologic examination in either group. Conclusion
      and significance Tonsil asymmetry may only be apparent in patients with an
      otherwise normal physical examination, secondary to benign hyperplasia or
      anatomical factors. Therefore, the presence of tonsil asymmetry without factors
      such as suspicious appearance, significant systemic signs and symptoms,
      progressive enlargement of the tonsil, concomitant neck adenopathies, and history
      of malignancy or immunocompromise, may not indicate malignancy, as a sole
      clinical feature.

PMID- 15243565
TI  - Adenotonsillectomy for obstructive sleep apnea in obese children.
AB  - OBJECTIVE: To study changes in sleep behavior and quality of life in obese
      children after adenotonsillectomy for obstructive sleep apnea. Study design and
      setting Prospective study at the University of New Mexico Children's Hospital.
      METHODS: Children who met inclusion criteria and had a respiratory distress index
      (RDI) greater than 5 were enrolled in the study and underwent adenotonsillectomy.
      All children underwent preoperative and postoperative full-night polysomnography.
      Age- and gender-specific percentile BMI was recorded at the time of
      polysomnography. Caregivers were asked to complete an OSA-18 quality of life
      survey prior to polysomnography and a second survey within 6 months of surgery.
      Scores from preoperative and postoperative polysomnography and OSA-18 surveys
      were compared using the paired Student's t test. RESULTS: The study population
      included 30 children. Twenty-six children (86%) were male. The mean age of the
      children at the time of inclusion in the study was 9.3 years; range, 3.0 to 17.2.
      The mean preoperative BMI was 28.6 (range, 19.2 to 47.1) and the mean
      postoperative BMI was 27.9 (range, 17.8 to 27.9). A 2-tailed paired t test showed
      that this difference is not statistically significant (P = 0.06). The mean
      preoperative RDI was 30.0 and the mean postoperative RDI was 11.6 (P < 0.001).
      The preoperative mean total OSA-18 score was 78.2 and the postoperative mean
      total score was 39.8 (P < 0.001). CONCLUSION: Obese children with OSA who undergo
      adenotonsillectomy show a marked improvement in RDI and in quality of life with
      no change in BMI. However, in the majority of children, OSA does not resolve.

PMID- 15243566
TI  - Postoperative infection in cochlear implant patients.
AB  - OBJECTIVE: Recently, the association of meningitis with cochlear implants has
      raised concern over the safety of these devices. We examined the incidence of all
      postoperative infections in patients undergoing cochlear implant surgery. Study
      design and settings A retrospective chart review of all patients undergoing
      cochlear implants at a private tertiary referral center from 1993 to 2002 was
      performed. Cochlear implant surgeries in 462 adults and 271 children were
      reviewed. Patients with evidence of a postoperative infection or infectious
      complication related to cochlear implantation were identified, and data on
      patient characteristics, surgery, and treatment outcome were obtained. RESULTS:
      The overall incidence of postoperative infection in our cochlear implant series
      was 4.1%. Major infectious complications occurred in 3.0% of cases, and the
      majority of infections required surgical intervention. A history of chronic ear
      disease may increase the risk of infectious complications. There were no cases of
      meningitis. CONCLUSIONS: Cochlear implants remain a safe procedure with a low
      complication rate. The majority of infections can be managed without removing the
      implant device. Advances in surgical technique and flap design have decreased the
      occurrence of wound-related complications. However, identification of risk
      factors for infection and optimization of treatment regimens will further reduce
      the complications associated with postoperative infection.

PMID- 15243567
TI  - Ototoxic protection of sodium thiosulfate: daily vs constant infusion.
AB  - OBJECTIVE: Compare the effect of a daily dose of sodium thiosulfate (STS) to
      continuous infusion of STS on Hartley albino guinea pig (HAGP) on cisplatin (CP)
      induced sensorineural hearing loss. Study design Prospective randomized pilot
      study comparing a single daily dose of STS to a constant controlled infusion of
      STS given the middle ear space (MES) with an ototoxic regimen of CP. The hearing
      thresholds will be obtained by auditory brainstem response (ABR) 1 week before
      and after treatment. Treatment effects on responses at 2, 8, and 16 kHz signals
      will be investigated by an analysis of variance with one between subjects'
      condition and two within subjects' conditions. SETTING: Basic science laboratory.
      RESULTS: STS protection resulted in significantly less hearing loss post
      treatment for the protected ears. Guinea pigs with continuous infusion of STS
      demonstrated less loss in the protected ear than those who received the single
      daily dose. As expected, hearing loss at 2 kHz was less than that at 8 and 16
      kHz. CONCLUSION: A continuous infusion of STS directly to the MES is better than
      a single daily dose of STS to the MES in reducing the ototoxicity of CP.
      SIGNIFICANCE: Any targeted protection, whether by continuous infusion or daily
      dose, is better than no protection against the sensorineural hearing loss of CP.

PMID- 15243568
TI  - Surgery of cerebellopontine angle epidermoid cysts: role of the widened
      retrolabyrinthine approach combined with endoscopy.
AB  - OBJECTIVES: To evaluate the use of the retrolabyrinthine approach (RLA) combined
      with endoscopy with particular reference to preservation of cranial nerve
      function and completeness of excision in surgery of epidermoid cysts. METHODS: A
      retrospective study was performed on a series of 8 consecutive patients of whom 7
      have undergone surgery. Main outcome measures Measures include audiological and
      neurological status preoperatively and postoperatively, size of the lesion, the
      surgical approach, completeness of excision, and operative morbidity. RESULTS:
      The tumors were all large, ranging from 2 x 3 cm to 6 x 6 cm. Presenting symptoms
      were headache (75%), dysequilibrium (62%), trigeminal nerve palsy (38%), abducens
      nerve palsy (25%), and, rarely, auditory symptoms. Seven patients underwent
      surgery, 5 by the RLA, 1 by a translabyrinthine approach (TLA), and 1 by a
      transcochlear approach. Complete excision was achieved in 5 of the 7 patients. A
      transtentorial approach was combined in 2 cases (1 RLA, 1 TLA). Endoscopy was
      used in 3 cases. It allowed a complete tumor excision. One case of keratinous
      meningitis was observed. Trigeminal nerve function returned to normal in all
      patients. Postoperative facial nerve function was grade I in 5 cases and grade
      III in 2 cases. Hearing was preserved in 3 cases as class A, 1 case as class B.
      In the 2 cases presenting with abducens nerve palsy preoperative symptoms were
      initially aggravated before returning to normal function by 1 year
      postoperatively. The RLA with endoscopy allowed less invasive surgery and
      preservation of hearing in 4 of the 5 cases where it was attempted. Tumor control
      appeared better than with the suboccipital approach. Mortality and postoperative
      morbidity also appear reduced. CONCLUSION: RLA combined with endoscopy should be
      considered as the standard approach for excision of epidermoid cysts. Extension
      of this approach into a TLA or transcochlear approach will depend on preoperative
      difficulties and preoperative hearing.

PMID- 15243569
TI  - Informed consent in functional endoscopic sinus surgery: the patient's
      perspective.
AB  - OBJECTIVE: Informed consent is essential prior to functional endoscopic sinus
      surgery (FESS). The content of this discussion is often determined by each
      surgeon. Many doctors discuss all potential complications. This may provoke
      anxiety or deter from beneficial surgery. Our goal was to examine the process
      from the patient's perspective. Study design A list of potential complications
      was reviewed with FESS patients. Patients were asked questions concerning their
      consent and the potential complications before and after FESS. RESULTS: Both
      before and after surgery, patients felt that discussion of most potential
      complications was important. Vision changes and cerebrospinal fluid leak (CSF)
      received the highest scores. No significant differences were found between
      primary and revision cases. CONCLUSION: Patients wanted most potential FESS
      complications to be discussed. Even though this triggered anxiety, they felt it
      was important to have a thorough disclosure. Findings presented may impact how
      surgeons counsel patients prior to FESS.

PMID- 15243570
TI  - Surgical management of paranasal sinus mucoceles: a long-term study of 60 cases.
AB  - Paranasal sinus mucocele is a benign pseudocystic lesion, which may originate
      from any of the sinus cavities. Although the diagnosis may be suggested by the
      clinical presentation, CT is necessary to accurately analyze the regional anatomy
      and extent of the lesion. MRI is helpful in defining the limited unusual lesions
      occurring in critical areas. Standard treatment is surgical marsupialization,
      through endonasal sinus surgery, which offers a conservative, minimally invasive
      approach, and respects the sinus architecture and natural drainage. Our long-term
      experience with the endonasal endoscopic approach for the treatment of mucoceles
      led us to subsequently expand our indications to include most mucoceles, either
      as the sole approach or associated with an external approach. Comprising the
      surgical experience of two collaborating universities, this paper describes the
      indications for the endonasal surgical approach and the long-term postoperative
      followup.

PMID- 15243571
TI  - Van der Woude syndrome: the most common cleft syndrome.

PMID- 15243572
TI  - Sarcoidosis of nasal ala and lower lip.

PMID- 15243573
TI  - Extensive laryngeal burn resulting from aspiration of gastric contents.

PMID- 15243576
TI  - A paradigm shift for erythropoietin: no longer a specialized growth factor, but
      rather an all-purpose tissue-protective agent.

PMID- 15243577
TI  - The vital osteoclast: how is it regulated?

PMID- 15243578
TI  - Cheating death: what can we learn from tumour resistance?

PMID- 15243579
TI  - The new kid on the block: the unfolded protein response in the pathogenesis of
      atherosclerosis.

PMID- 15243580
TI  - Erythropoietin as an antiapoptotic, tissue-protective cytokine.
AB  - Erythropoietin (EPO) increases the number of circulating erythrocytes primarily
      by preventing apoptosis of erythroid progenitors. In addition to this
      proerythroid action, results of recent studies show that systemically
      administered EPO is protective in vivo, in several animal models of neuronal
      injury. In vitro, EPO prevents neuronal apoptosis induced by a variety of
      stimuli. This review summarizes the neuroprotective actions of EPO and discusses
      the underlying mechanisms in terms of signal transduction pathways involved. The
      understanding of these mechanisms will help differentiate the neuroprotective
      actions of EPO from its role in the bone marrow.

PMID- 15243581
TI  - Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular
      mechanisms and clinical relevance.
AB  - The ability of glucocorticoids (GC) to efficiently kill lymphoid cells has led to
      their inclusion in essentially all chemotherapy protocols for lymphoid
      malignancies. This review summarizes recent findings related to the molecular
      basis of GC-induced apoptosis and GC resistance, and discusses their potential
      clinical implications. Accumulating evidence suggests that GC may induce cell
      death via different pathways resulting in apoptotic or necrotic morphologies,
      depending on the availability/responsiveness of the apoptotic machinery. The
      former might result from regulation of typical apoptosis genes such as members of
      the Bcl-2 family, the latter from detrimental GC effects on essential cellular
      functions possibly perpetuated by GC receptor (GR) autoinduction. Although other
      possibilities exist, GC resistance might frequently result from defective GR
      expression, perhaps the most efficient means to target multiple antileukemic GC
      effects. Numerous novel drug combinations are currently being tested to prevent
      resistance and improve GC efficacy in the therapy of lymphoid malignancies.

PMID- 15243582
TI  - Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic
      disease.
AB  - Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular
      disease, including ischemic heart disease, stroke, and peripheral vascular
      disease. Mutations in the enzymes responsible for homocysteine metabolism,
      particularly cystathionine beta-synthase (CBS) or 5,10-methylenetetrahydrofolate
      reductase (MTHFR), result in severe forms of HHcy. Additionally, nutritional
      deficiencies in B vitamin cofactors required for homocysteine metabolism,
      including folic acid, vitamin B6 (pyridoxal phosphate), and/or B12
      (methylcobalamin), can induce HHcy. Studies using animal models of genetic- and
      diet-induced HHcy have recently demonstrated a causal relationship between HHcy,
      endothelial dysfunction, and accelerated atherosclerosis. Dietary enrichment in B
      vitamins attenuates these adverse effects of HHcy. Although oxidative stress and
      activation of proinflammatory factors have been proposed to explain the
      atherogenic effects of HHcy, recent in vitro and in vivo studies demonstrate that
      HHcy induces endoplasmic reticulum (ER) stress, leading to activation of the
      unfolded protein response (UPR). This review summarizes the current role of HHcy
      in endothelial dysfunction and explores the cellular mechanisms, including ER
      stress, that contribute to atherothrombosis.

PMID- 15243583
TI  - Irradiation-induced progenitor cell death in the developing brain is resistant to
      erythropoietin treatment and caspase inhibition.
AB  - One hemisphere of postnatal day 8 (P8) rats or P10 mice was irradiated with a
      single dose of 4-12 Gy, and animals were killed from 2 h to 8 weeks after
      irradiation (IR). In the subventricular zone (SVZ) and the granular cell layer
      (GCL) of the dentate gyrus, harboring neural and other progenitor cells,
      nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active
      caspase-3, apoptosis-inducing factor and TUNEL (6-24 h). Ki67-positive
      (proliferating) cells had disappeared by 12 h and partly reappeared by 7 days
      post-IR. The SVZ and GCL areas decreased approximately 50% 7 days after IR. The
      development of white matter was hampered, resulting in 50-70% less myelin basic
      protein staining. Pretreatment with erythropoietin did not confer protection
      against IR. Caspase inhibition by overexpression of XIAP prevented caspase-9 and
      caspase-3 activation but not cell death, presumably because of increased caspase
      independent cell death.

PMID- 15243584
TI  - PI3K mediates protection against TRAIL-induced apoptosis in primary human
      melanocytes.
AB  - Melanocytes are cells of the epidermis that synthesize melanin, which is
      responsible for skin pigmentation. Transformation of melanocytes leads to
      melanoma, a highly aggressive neoplasm, which displays resistance to apoptosis.
      In this report, we demonstrate that TNF-related apoptosis-inducing ligand
      (TRAIL), which was thought to kill only transformed cells, promotes very
      efficiently apoptosis of primary human melanocytes, leading to activation of
      caspases 8, 9 and 3, and the cleavage of vital proteins. Further, we show that
      stem cell factor (SCF), a physiologic melanocyte growth factor that activates
      both the phosphatidyl-inositol-3 kinase (PI3K) and the extracellular regulated
      kinase (ERK) pathways, strongly protects melanocytes from TRAIL and staurosporine
      killing. Interestingly, inhibition of PI3K or its downstream target AKT
      completely blocks the antiapoptotic effect of SCF, while inhibition of ERK has
      only a moderate effect. Our data indicate that protection evoked by SCF/PI3K/AKT
      cascade is not mediated by an increase in the intracellular level of FLIP.
      Further, only a sustained PI3K activity can protect melanocytes from apoptosis,
      thereby indicating that the PI3K/AKT pathway plays a pivotal role in melanocyte
      survival. The results gathered in this report bring new information on the
      molecular mechanisms involved in primary melanocyte apoptosis and survival that
      would help to better understand the process by which melanomas acquire their
      resistance to apoptosis.

PMID- 15243585
TI  - p53 and its family members -- reporter genes may not see the difference.

PMID- 15243586
TI  - Occlusal seduction.

PMID- 15243587
TI  - Clinical waste companies.

PMID- 15243588
TI  - A view from overseas.

PMID- 15243598
TI  - How relevant is counselling in relation to dentistry?
AB  - This article attempts to explain reasons behind the general public's fear of
      dentistry by examining the historical perspective and, using case scenarios,
      demonstrates areas where patients' dental treatment might have been helped by the
      use of counselling. Distinguishing between the use of counselling skills vis-a
      vis professional counselling, the wider issues for the dental profession -
      education, boundaries and the need for referrals - are explored. It is suggested
      that if a counsellor were included as part of the dental team, patients and
      professionals would benefit. The counsellor could act as an advisor and educator
      for the team in addition to undertaking professional counselling on referral.
      Patients with anxiety or phobias could be recognised and helped appropriately and
      occupational stress experienced by practitioners would be reduced.

PMID- 15243599
TI  - Research in primary dental care. Part 5: devising a proposal, obtaining funding
      and ethical considerations.
AB  - In previous articles, we have considered how to formulate a research question and
      choose an appropriate methodological approach to answer that question, including
      the use of evidence-based research instruments or measurement scales. In this
      article, we put this information together in the form of a research proposal and
      consider how to obtain funding for the research project, as well as fulfil
      ethical requirements.

PMID- 15243600
TI  - A qualitative exploration of dental practitioners' knowledge, attitudes and
      practices towards HIV+ and patients with other 'high risk' groups.
AB  - This paper expands upon a previous quantitative study which measured dentists'
      knowledge, attitudes and practices towards patients carrying blood-borne viruses
      in order to identify potential barriers to the provision of adequate dental
      treatment. Although some useful findings were obtained in that study, it was
      suggested that further qualitative work needed to be conducted in order to
      provide the opportunity for dental practitioners' to expand, reflect and justify
      their opinions and beliefs in more detail. The aim of this study is to present
      the results of such a qualitative investigation.

PMID- 15243608
TI  - Treatment of temporomandibular disorders by stabilising splints in general dental
      practice: results after initial treatment.
AB  - INTRODUCTION: Little is known about how effective general dental practitioners
      (GDPs) are in treating temporomandibular disorders (TMD). The overall aim of this
      study was to compare the lower stabilising splint (SS) with a non-occluding
      control (CS) for the management of TMD in general dental practice. METHOD: A
      total of 93 TMD patients attending 11 GDPs were randomly allocated to SS or CS.
      Diagnosis was according to International Headache Society Criteria. Outcome
      criteria included pain visual analogue scale (VAS), number of tender muscles,
      aggregate joint tenderness, inter-incisal opening, TMJ clicks and headaches.
      Splints were fitted one week after baseline and patients were followed-up every
      three weeks to three months; those not responding to CS after six weeks (< 50%
      VAS reduction) were crossed over to SS for a further three months. RESULTS:
      Documentation was returned from nine GDPs for 72 patients (38 for SS, 34 for CS).
      At six weeks, mean improvements were noted for all outcome criteria, but less so
      for clicking. There were no significant differences between splints [chi(2)].
      Seventeen CS patients had < 50% VAS reduction and were provided with SS in the
      cross-over group. CS patients with >50% VAS reduction were significantly younger
      than CS patients who crossed-over (ANOVA, p=0.009) and had significantly less
      diagnoses of TMJ clicking (chi(2), p<0.05). At the conclusion of the trial 16
      patients were referred for specialist management: 11 non-responders (< 50% VAS
      reduction), one of whom needed occlusal adjustment and five responders also
      needing occlusal adjustment. CONCLUSIONS: At six weeks SS gave similar relief to
      CS for all outcome criteria. Patients who crossed-over from CS to SS were more
      likely to be older and have clicking TMJs. At the end of treatment nine of 11 non
      responders to SS had a diagnosis of disc displacement with reduction. However,
      80% TMD patients were managed effectively by GDPs using splints for periods of up
      to five months.

PMID- 15243609
TI  - A prospective randomised cross-over study of the effect of local haemostasis
      after third molar surgery on facial swelling: an exploratory trial.
AB  - OBJECTIVE: This study was undertaken in order to evaluate the effects of local
      haemostasis on the facial swelling induced in patients undergoing surgical
      removal of impacted mandibular third molar teeth. DESIGN: A prospective
      randomised cross-over study. SETTING: Department of Oral and Maxillofacial
      Surgery, Samsun, Turkey, 2002. MATERIALS AND METHODS: Twenty-five healthy
      patients who were having bilaterally symmetric, impacted third molar extraction
      were studied. The teeth were removed in two separate operations by two surgeons
      who had equal academic degrees. The patients were assigned to test and control
      groups by random selection. One side served as control and on the other local
      haemostasis was achieved by a haemostatic agent (oxidised regenerated cellulose).
      This was placed into the socket following gauze packing for 3 minutes (test). The
      operating time therefore significantly increased in the test group. Data was
      collected regarding the operating time, mouth opening and facial swelling.
      RESULTS: There were no statistically significant differences between the test and
      control groups for the mean values of the facial swelling and mouth opening at
      day 1 and 3 post-operatively (P > 0.05). Operating time was statistically longer
      for the test group than the control (P < 0.001). CONCLUSION: This study has shown
      that establishment of local haemostasis after removal of impacted mandibular
      third molars is not so effective in preventing facial swelling.

PMID- 15243610
TI  - Articaine and lignocaine efficiency in infiltration anaesthesia: a pilot study.
AB  - AIM: The purpose of this study was to evaluate the onset of action of pulpal and
      soft tissue anaesthesia, and pain experience after buccal and palatal
      infiltrative injections with 4% articaine with 1:100,000 adrenaline, and 2%
      lignocaine with 1:100,000 adrenaline. METHOD: A double blind cross-over study was
      conducted with 20 healthy adult subjects who, in two appointments at least two
      weeks apart, randomly received an infiltration anaesthesia with the solutions in
      the buccal and palatal regions of the upper right canine. The tooth was tested
      with a pulp tester before (to establish its baseline response), and after the
      injection, until return to the base threshold level. The pain experience caused
      by palatal injection was verified by the visual analogue scale (VAS). Data were
      analysed using Wilcoxons test (alpha = 0.05). RESULTS: There were no significant
      statistical differences between the solutions with respect to VAS (p = 0.45),
      onset of action (p = 0.80) and pulpal (p = 0.08) and soft tissue (p = 0.18)
      anaesthesia duration, although pulpal anaesthesia may have reached statistical
      significance if a higher number of volunteers had been used. CONCLUSION: Under
      the conditions of this study it can be concluded that both anaesthetic solutions
      showed similar pain experience.

PMID- 15243628
TI  - Crystal structure of a complex between anthrax toxin and its host cell receptor.
AB  - Anthrax toxin consists of the proteins protective antigen (PA), lethal factor
      (LF) and oedema factor (EF). The first step of toxin entry into host cells is the
      recognition by PA of a receptor on the surface of the target cell. Subsequent
      cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric
      PA63 pre-pore, which triggers endocytosis. Upon acidification of the endosome,
      PA63 forms a pore that inserts into the membrane and translocates EF and LF into
      the cytosol. Two closely related host cell receptors, TEM8 and CMG2, have been
      identified. Both bind to PA with high affinity and are capable of mediating
      toxicity. Here, we report the crystal structure of the PA-CMG2 complex at 2.5 A
      resolution. The structure reveals an extensive receptor-pathogen interaction
      surface mimicking the non-pathogenic recognition of the extracellular matrix by
      integrins. The binding surface is closely conserved in the two receptors and
      across species, but is quite different in the integrin domains, explaining the
      specificity of the interaction. CMG2 engages two domains of PA, and modelling of
      the receptor-bound PA63 heptamer suggests that the receptor acts as a pH
      sensitive brace to ensure accurate and timely membrane insertion. The structure
      provides new leads for the discovery of anthrax anti-toxins, and should aid the
      design of cancer therapeutics.

PMID- 15243629
TI  - Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV
      1.
AB  - In Old World primates, TRIM5-alpha confers a potent block to human
      immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into
      cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar
      activity in human cells. Among New World primates, only owl monkeys exhibit post
      entry restriction of HIV-1 (ref. 1). Paradoxically, the barrier to HIV-1 in owl
      monkey cells is released by capsid mutants or drugs that disrupt capsid
      interaction with CypA. Here we show that knockdown of owl monkey CypA by RNA
      interference (RNAi) correlates with suppression of anti-HIV-1 activity. However,
      reintroduction of CypA protein to RNAi-treated cells did not restore antiviral
      activity. A search for additional RNAi targets unearthed TRIMCyp, an RNAi
      responsive messenger RNA encoding a TRIM5-CypA fusion protein. TRIMCyp accounts
      for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection
      when transferred to otherwise infectable human or rat cells. It seems that
      TRIMCyp arose after the divergence of New and Old World primates when a LINE-1
      retrotransposon catalysed the insertion of a CypA complementary DNA into the
      TRIM5 locus. This is the first vertebrate example of a chimaeric gene generated
      by this mechanism of exon shuffling.

PMID- 15243630
TI  - Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in
      carcinoma derived cell lines.
AB  - EGP-2, also known as Ep-CAM, is expressed at high levels on the surface of most
      carcinomas and is therefore considered an attractive target for anticancer
      strategies. To explore the mechanisms regulating the expression of EGP-2,
      sequences 3.4 kb upstream of the transcription start site were isolated and
      assayed for their ability to control the expression of the EGP-2 cDNA, the green
      fluorescent protein, the luciferase reporter gene and the thymidine kinase and
      cytosine deaminase suicide genes. Expression of these chimeric constructs as
      assessed in a range of different cell lines was restricted to cell lines
      expressing EGP-2. In addition, only cells expressing EGP-2 were sensitive for
      gancyclovir after being transiently transfected with EGP-2 promoter-driven
      thymidine kinase. Deletion analyses defined 687 bp upstream as the basic proximal
      promoter region, which could confer epithelial-specific expression to the GFP
      reporter gene in vitro. As these EGP-2 sequences can confer promoter activity to
      reporter and suicide genes in an EGP-2 restricted manner, they may be useful for
      gene therapy of EGP-2 expressing carcinomas.

PMID- 15243631
TI  - Functional expression of thymidine kinase in human leukaemic and colorectal
      cells, delivered as EGFP fusion protein by herpesvirus saimiri-based vector.
AB  - Herpesvirus saimiri (HVS) has the capacity to incorporate large amounts of
      heterologous DNA and can infect many different human cell types. To develop its
      potential as a gene therapy vector, we cloned herpes simplex virus thymidine
      kinase (TK) gene into the HVS genome in the form of an enhanced green fluorescent
      protein (EGFP) fusion protein, using a cosmid-based approach. At multiplicity of
      infection = 100 over 90% of human leukemic K562 and Jurkat cells were transduced
      with HVS/EGFP-TK. Conditions of no selective pressure expression were maintained
      at > 92% per cell division. Expression of the EGFP-TK fusion protein rendered
      transfected leukaemic cells sensitive to cytotoxic treatment with the prodrugs
      ganciclovir (GCV) and (E)-5-(2-bromovinyl)-2'deoxyuridine (BVDU) at
      concentrations as low as 10 ng/ml. The viral vector was also screened against a
      panel of colorectal and pancreatic carcinoma cell lines. All cell lines were
      transduced but showed a range of sensitivity to infection. Three of the most
      easily transduced cell lines: Mia PaCa, HCT116 and SW948 transduced with HVS/EGFP
      TK were effectively ablated by subsequent treatment with GCV or BVDU. Our results
      show that in its current form HVS/EGFP-TK could be utilized as an antitumour
      agent, or it could be developed further by inclusion of a therapeutic gene, with
      TK presence ensuring a mechanism of controlled removal of modified cells when no
      longer necessary. These results suggest that HVS/EGFP-TK has a great potential
      for a number of gene therapy applications.

PMID- 15243632
TI  - Means, not ends.

PMID- 15243633
TI  - The Academy of Health Information Professionals: ripe for research.

PMID- 15243634
TI  - Race and librarianship: part I.

PMID- 15243635
TI  - Joanne Gard Marshall, AHIP, FMLA Medical Library Association President 2004-2005.

PMID- 15243636
TI  - Update on inflation of journal prices: Brandon/Hill list journals and the
      scientific, technical, and medical publishing market.
AB  - OBJECTIVE: The original study of journal prices, using the "Brandon/ Hill
      Selected List of Books and Journals for the Small Medical Library," was first
      published in 1980 and periodically updated. This research continues to measure
      price increases for these titles for the periods 1996 to 1999 and 1999 to 2002.
      METHODOLOGY: The 111 journal titles that have appeared in each published list
      from 1967 to 2001 were included in the study. Institutional subscription price
      data were gathered for each journal for the years 1996, 1999, and 2002 and were
      compared to the Consumer Price Index (CPI) for the same years. RESULTS: The
      average journal price continues to rise significantly and is independent of the
      CPI. The study found that prices have jumped 51.9% from 1996 to 1999 and 32% from
      1999 to 2002, which is consistent with nearly every recent journal price study.
      CONCLUSION: The unprecedented rise in journal prices negatively affects the
      purchasing power of medical libraries. This paper examines the economic and
      technological pressures on the science, technology, and medical journals market
      that contribute to high prices and identifies a number of initiatives in the
      biological and health sciences that utilize alternative models for disseminating
      scientific research.

PMID- 15243637
TI  - Quality markers and use of electronic journals in an academic health sciences
      library.
AB  - OBJECTIVES: Patterns of use of electronic versions of journals supplied by an
      academic health sciences library were examined to determine whether they differed
      from patterns of use among corresponding print titles and to relate the
      applicability of print collection development practices to an electronic
      environment. METHODS: Use data supplied by three major vendors of electronic
      journals were compared to reshelving data for corresponding print titles, impact
      factors, and presence on Brandon/Hill Lists. RESULTS: In collections where one
      click access from a database record to the full text of articles was possible,
      electronic use correlated with print use across journal pairs. In both versions,
      Brandon/Hill titles were used more frequently than non-Brandon/Hill titles, use
      had modest correlations with journals' impact factors, and clinical use appeared
      to be higher than research use. Titles that had not been selected for the
      library's print collections, but which were bundled into publishers' packages,
      received little use compared to electronic titles also selected in print.
      CONCLUSIONS: Collection development practices based on quality and user needs can
      be applied with confidence to the electronic environment. Facilitating direct
      connections between citation databases and the corresponding journal articles
      regardless of platform or publisher will support scholarship and quality health
      care.

PMID- 15243638
TI  - Health sciences librarians' attitudes toward the Academy of Health Information
      Professionals.
AB  - OBJECTIVES: The purpose of the study was to ascertain health sciences librarians'
      attitudes toward the Academy of Health Information Professionals (AHIP). SAMPLE:
      Systematic sampling was used to select 210 names from the list of members of the
      Midwest Chapter of the Medical Library Association. METHODS: A questionnaire
      containing open- and closed-ended questions was used to collect the data.
      RESULTS: A total of 135 usable questionnaires were returned. Of the respondents,
      34.8% are members of the academy and most are at the senior or distinguished
      member levels. The academy gives them a sense of professionalism and helps them
      to keep current with new trends. The majority of participants (65.2%) are not
      members of the academy. Among the various reasons proffered are that neither
      institutions nor employers require it and that there is no obvious benefit to
      belonging to the academy. CONCLUSIONS: More research needs to be done with a
      larger sample size to determine the attitudes of health sciences librarians,
      nationwide, toward the academy.

PMID- 15243639
TI  - Information-seeking behavior changes in community-based teaching practices.
AB  - A National Library of Medicine information access grant allowed for a
      collaborative project to provide computer resources in fourteen clinical practice
      sites that enabled health care professionals to access medical information via
      PubMed and the Internet. Health care professionals were taught how to access
      quality, cost-effective information that was user friendly and would result in
      improved patient care. Selected sites were located in medically underserved areas
      and received a computer, a printer, and, during year one, a fax machine.
      Participants were provided dial-up Internet service or were connected to the
      affiliated hospital's network. Clinicians were trained in how to search PubMed as
      a tool for practicing evidence-based medicine and to support clinical decision
      making. Health care providers were also taught how to find patient-education
      materials and continuing education programs and how to network with other
      professionals. Prior to the training, participants completed a questionnaire to
      assess their computer skills and familiarity with searching the Internet,
      MEDLINE, and other health-related databases. Responses indicated favorable
      changes in information-seeking behavior, including an increased frequency in
      conducting MEDLINE searches and Internet searches for work-related information.

PMID- 15243640
TI  - The use of personal digital assistants in the health sciences: results of a
      survey.
AB  - OBJECTIVES: The purpose of this study is to determine how personal digital
      assistants (PDAs) are used on an academic health sciences campus to define the
      level of training and support the library can provide to the students and
      faculty. METHOD: A Web-based questionnaire was developed. A total of 1,538 health
      sciences faculty and residents were sent an email message requesting
      participation. Data from the returned surveys were analyzed with SPSS. RESULTS:
      Sixty-one percent of survey respondents used PDAs. The address book, date book,
      and calculator were the most common uses reported for PDAs. Residents also
      reported a high use of drug databases on their PDAs. Most survey respondents
      indicated they would like to learn more about clinical resources for PDAs.
      CONCLUSIONS: Many opportunities exist for librarians to provide training and
      support for PDAs, in addition to evaluation and promotion of clinical software
      for PDAs.

PMID- 15243641
TI  - Comparison of Medical Subject Headings and text-word searches in MEDLINE to
      retrieve studies on sleep in healthy individuals.
AB  - OBJECTIVE: The objective was to investigate the performance of two search
      strategies in the retrieval of primary research papers containing descriptive
      information on the sleep of healthy people from MEDLINE. METHODOLOGY: Two search
      strategies-one based on the use of only Medical Subject Headings (MeSH), the
      second based on text-word searching-were evaluated as to their specificity and
      sensitivity in retrieving a set of relevant research papers published in the
      journal Sleep from 1996 to 2001 that were preselected by a hand search. RESULTS:
      The subject search provided higher specificity than the text-word search (66% and
      47%, respectively) but lower sensitivity (78% for the subject search versus 88%
      for the text-word search). Each search strategy gave some unique relevant hits.
      CONCLUSIONS: The two search strategies complemented each other and should be used
      together for maximal retrieval. No combination of MeSH terms could provide
      comprehensive yet reasonably precise retrieval of relevant articles. The text
      word searching had sensitivity and specificity comparable to the subject search.
      In addition, use of text words "normal," "healthy," and "control" in the title or
      abstract fields to limit the final sets provided an efficient way to increase the
      specificity of both search strategies.

PMID- 15243642
TI  - Issues surrounding the administration of a credit course for medical students:
      survey of US academic health sciences librarians.
AB  - OBJECTIVES: For librarians developing a credit course for medical students, the
      process often involves trial and error. This project identified issues
      surrounding the administration of a credit course, so that librarians nationally
      can rely more upon shared knowledge of common practices and less upon trial and
      error. METHODS: A questionnaire was sent to the education services librarian at
      each medical school listed in the 2000 AAMC Data Book. A second questionnaire was
      sent to those librarians who did not return the first one. RESULTS: Of the 125
      librarians surveyed, 82 returned the questionnaire. Of those 82, only 11 offered
      a credit course for medical students, though 19 more were in the process of
      developing one. Data were gathered on the following aspects of course
      administration: credit course offerings, course listing, information learned to
      administer the course, costs associated with the course, relationships with other
      departments on campus, preparation for teaching and grading, and evaluation of
      the course. CONCLUSIONS: Because of small number of respondents offering a credit
      course and institutional variations, making generalizations about issues
      surrounding the administration of a credit course is difficult. The article
      closes with a list of recommendations for librarians planning to develop a
      course.

PMID- 15243643
TI  - The introduction, methods, results, and discussion (IMRAD) structure: a fifty
      year survey.
AB  - BACKGROUND: The scientific article in the health sciences evolved from the letter
      form and purely descriptive style in the seventeenth century to a very
      standardized structure in the twentieth century known as introduction, methods,
      results, and discussion (IMRAD). The pace in which this structure began to be
      used and when it became the most used standard of today's scientific discourse in
      the health sciences is not well established. PURPOSE: The purpose of this study
      is to point out the period in time during which the IMRAD structure was
      definitively and widely adopted in medical scientific writing. METHODS: In a
      cross-sectional study, the frequency of articles written under the IMRAD
      structure was measured from 1935 to 1985 in a randomly selected sample of
      articles published in four leading journals in internal medicine: the British
      Medical Journal, JAMA, The Lancet, and the New England Journal of Medicine.
      RESULTS: The IMRAD structure, in those journals, began to be used in the 1940s.
      In the 1970s, it reached 80% and, in the 1980s, was the only pattern adopted in
      original papers. CONCLUSIONS: Although recommended since the beginning of the
      twentieth century, the IMRAD structure was adopted as a majority only in the
      1970s. The influence of other disciplines and the recommendations of editors are
      among the facts that contributed to authors adhering to it.

PMID- 15243644
TI  - Current findings from research on structured abstracts.
AB  - BACKGROUND: Structured abstracts were introduced into medical research journals
      in the mid 1980s. Since then they have been widely used in this and other
      contexts. AIM: The aim of this paper is to summarize the main findings from
      research on structured abstracts and to discuss the limitations of some aspects
      of this research. METHOD: A narrative literature review of all of the relevant
      papers known to the author was conducted. RESULTS: Structured abstracts are
      typically longer than traditional ones, but they are also judged to be more
      informative and accessible. Authors and readers also judge them to be more useful
      than traditional abstracts. However, not all studies use "real-life" published
      examples from different authors in their work, and more work needs to be done in
      some cases. CONCLUSIONS: The findings generally support the notion that
      structured abstracts can be profitably introduced into research journals. Some
      arguments for this, however, have more research support than others.

PMID- 15243645
TI  - Consumer health information provided by library and hospital Websites in the
      South Central Region.

PMID- 15243646
TI  - Delivery of Web-based instruction using Blackboard: a collaborative project.

PMID- 15243647
TI  - Two different point mutations in ABL gene ATP-binding domain conferring Primary
      Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report.
AB  - Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients.
      Point mutations have been detected in ATP-binding domain of ABL gene which
      disturbs the binding of Gleevec to this target leading to resistance. Detection
      of mutations is helpful in clinical management of imatinib resistance. We
      established a very sensitive (ASO) PCR to detect mutations in an imatinib
      resistant CML patient. Mutations C944T and T1052C were detected which cause
      complete partial imatinib resistance, respectively. This is the first report of
      multiple point mutations conferring primary imatinib resistance in same patient
      at the same time. Understanding the biological reasons of primary imatinib
      resistance is one of the emerging issues of pharmacogenomics and will be helpful
      in understanding primary resistance of molecularly-targeted cancer therapies. It
      will also be of great utilization in clinical management of imatinib resistance.
      Moreover, this ASO-PCR assay is very effective in detecting mutations related to
      imatinib resistance.

PMID- 15243649
TI  - Flow cytometry based techniques to study testicular acidophilic granulocytes from
      the protandrous fish gilthead seabream (Sparus aurata L.).
AB  - The gilthead seabream is a protandrous seasonal breeding teleost that is an
      excellent model for studying the testicular regression process which occurs in
      both seasonal testicular involution and sex reversion. Little is known about the
      cell types and the molecular mechanisms involved in such processes, mainly
      because of the lack of appropriate methods for testis dissociation, and
      testicular cell isolation, culture and functional characterization. We have
      previously reported that gilthead seabream acidophilic granulocytes infiltrate
      the testis at post-spawning stage, settle close to the spermatogonia and
      accumulate intracellular interleukin-1beta. In this paper, we report several flow
      cytometry based assays which allow to establish the role played by gilthead
      seabream testicular acidophilic granulocytes and permits their quantification.

PMID- 15243648
TI  - Use of Ion-Channel Modulating Agents to Study Cyanobacterial Na(+) - K(+) Fluxes.
AB  - Here we describe an experimental design aimed to investigate changes in total
      cellular levels of Na(+) and K(+) ions in cultures of freshwater filamentous
      cyanobacteria. Ion concentrations were measured in whole cells by flame
      photometry. Cellular Na(+) levels increased exponentially with rising alkalinity,
      with K(+) levels being maximal for optimal growth pH (~8). At standardized pH
      conditions, the increase in cellular Na(+), as induced by NaCl at 10 mM, was
      coupled by the two sodium channel-modulating agents lidocaine hydrochloride at 1
      microM and veratridine at 100 microM. Both the channel-blockers amiloride (1 mM)
      and saxitoxin (1 microM), decreased cell-bound Na(+) and K(+) levels. Results
      presented demonstrate the robustness of well-defined channel blockers and channel
      activators in the study of cyanobacterial Na(+)- K(+) fluxes.

PMID- 15243650
TI  - Dynamic force microscopy for imaging of viruses under physiological conditions.
AB  - Dynamic force microscopy (DFM) allows imaging of the structure and the assessment
      of the function of biological specimens in their physiological environment. In
      DFM, the cantilever is oscillated at a given frequency and touches the sample
      only at the end of its downward movement. Accordingly, the problem of lateral
      forces displacing or even destroying bio-molecules is virtually inexistent as the
      contact time and friction forces are reduced. Here, we describe the use of DFM in
      studies of human rhinovirus serotype 2 (HRV2) weakly adhering to mica surfaces.
      The capsid of HRV2 was reproducibly imaged without any displacement of the virus.
      Release of the genomic RNA from the virions was initiated by exposure to low pH
      buffer and snapshots of the extrusion process were obtained. In the following,
      the technical details of previous DFM investigations of HRV2 are summarized.

PMID- 15243651
TI  - [Cognitive therapy in patients with obsessive ruminations].
AB  - The article stands out the elevate amount of patients with obsessive-compulsive
      disorder who only or mainly present obsessive ruminations. Firstly, the basic
      concepts of behavioral model of obsessive-compulsive disorder are enunciated. In
      the second place, the limitations of behavioural treatment for patient with
      obsessive ruminations are discussed. Then, the general characteristics of
      cognitive model of compulsive-obsessive dysfunction are formulated. Finally,
      steps of cognitive treatment for patient with obsessive ruminations are outlined.

PMID- 15243652
TI  - [Glutamatergic neurotransmission, depression and antidepressants].
AB  - Depression is a psychiatric disorder that affects 20% of the population. Despite
      the efforts aimed to identify the mechanisms underlying its behavioral and
      affective symptoms, no consensus has been reached. In the last years two new
      theories, the glutamatergic and the genomic ones, have been proposed. Upon the
      first, the exposition to stressful stimuli increases hippocampal glutamatergic
      neurotransmission and triggers excitotoxic changes. The second one postulates
      that depression is closely correlated with neuronal atrophy due to a decrease in
      BDNF. The aim of this work is to review recent findings about the glutamatergic
      neurotransmission and its implication in animal models of depression, depressed
      patients and in both conditions after the antidepressant treatment. We also tried
      to identify possible links between these observations and the genomic theory.

PMID- 15243653
TI  - [Survey of attitudes to air travel after terrorist events of September 2001].
AB  - An opportunistic questionnaire study of peoples attitudes to, commercial flying
      and their behavioural responses after the events of September 11 2001 in the USA.
      Cohorts drawn from people attending a series of educational lectures, a specific
      leisure time activity and a travel health clinic 6 months after the disasters.
      More people appeared to worry about air travel 6 months after Sept 11 2001 than
      in reports prior to this date and the worried seem to experience a greater
      intensity of anxiety.

PMID- 15243654
TI  - [Early experiences and environment: their impact on neurodevelopment and the
      creation of mental processes].
AB  - Neurosciences have contributed to give support to the significance objects
      (mother, father, among others), affects, environment and different early
      experiences have in the unfolding and development of the child's mental structure
      and in this manner to throw light on intersubjective and intrapsychic
      relationships. This review focused on the impact of early mothering experiences
      and of the environment on molecular events linked to the processes of
      neurogenesis, synaptogenesis and the construction of circuits of processing and
      signalling, mainly in the hippocampus (structure connected with the processes of
      learning, memory and the control of response to stressors). Therefore, normal
      development,as well as mental pathology, is not the mere result from the action
      of present stressors (synchronic view), but its deepest roots lie in the matrix
      generated by the early experiences between mother and child and the environment
      inputs (diachronic view). Therefore, early experience, as well as secure
      attachment, can modulate the individual resilience in the face of future
      adversity.

PMID- 15243655
TI  - [Endemic social exclusion and early development: "made in Chacarita"].
AB  - My aim is to introduce in this article a project that two foundations are
      developing in Chacarita, a neighborhood in Buenos Aires City, heading to provide
      help and support to adolescent parents under social deprivation conditions and/or
      undergoing emotional problems. It is an action project embracing different
      strategies to work on the prevention of infant psychopathological disorders as
      well as the parenting process. The aspects on early development on children are
      specially emphasized describing the interventions to promote the development and
      the care of the protective factors, the resilience, as well as to approach the
      risk factors. This is illustrated threw a clinical case.

PMID- 15243656
TI  - [Importance of attachment in the development of psychism].
AB  - John Bowlby refers to attachment as the special affect and trust bond that a
      child establishes with other emotionally significant people, who constitute a
      source of security and protection. The main figure of attachment during childhood
      is generally the person who fulfills the maternal function (primary caregiver),
      although it is also established with the father, brothers/sisters, grandparents,
      and others. The approaching behavior could be activated by different stimuli
      which depends on each person and his/her developing stage. This bond is developed
      according to experiences and relationships in the first years of life -
      experiences stored in mental representations (internal working models), which
      influence the individual's psychic organization. Different instruments allow to
      make evident the different types of attachment bonds and to establish a
      correlation between parents and children. The Attachment makes up a valid
      theoretical and methodological model for the investigation, prevention and
      treatment in mental health.

PMID- 15243657
TI  - [Malnutrition, environment and children's development].
AB  - Protein energy malnutrition (PME) affects negatively children's somatic and
      cognitive development. Micronutrient deficiencies which usually coexist with PEM
      also have a negative influence on the cognitive development of children. The
      social and familiar environment in which disadvantaged children usually grow is
      very poor from the point of view of psychological and sensorial stimulation. All
      these factors together severely impede the full expression of poor children's
      genetic potential.

PMID- 15243658
TI  - [W. Bion's contribution to the discussion on nature vs. nurture. Early
      development and psychosis].
AB  - This papers presents a Mother-baby model of interaction that generates the
      capacity to think, linked to emotional life. With this model is possible to
      shorten the distances between those who think that mental pathology is caused by
      constitutional factors and those who use the "tabula rasa" model and assume that
      the environment failures are the cause of the pathology. The relation between
      concreteness and abstraction is explored as the basis for the capacity to mental
      development.

PMID- 15243659
TI  - [A baby is opening a door for us". Interview with Bernard Golse].

PMID- 15243660
TI  - [Social crisis, human rights and public hospital].

PMID- 15243661
TI  - [Tuberculosis contact tracing among children and adolescents, Brazil].
AB  - OBJECTIVE: To detect tuberculosis (TB) disease or infection among contacts of
      pulmonary TB patients. METHODS: Cross-sectional study in a Primary Healthcare
      unit in Rio de Janeiro (Brazil) with 184 child and adolescent contacts of
      pulmonary TB patients between March 1995 and March 1997. Subjects underwent
      clinical evaluation, chest radiographs, and tuberculin skin tests (TST); sputum
      smears were performed whenever possible. TB cases found were submitted to
      treatment and infected patients to chemoprophylaxis. Tuberculin converters, who
      tested positive for TST eight weeks after an initial negative result, received
      chemoprophylaxis. RESULTS: The sample included 98 boys and 86 girls; age ranged
      from 0 to 15 years; 26.9% were malnourished according to the Gomez criteria.
      Concerning the source of infection, 170 cases (92.4%) had household contacts, of
      which 66.5% were the child's parents. BCG vaccination was verified in 98.4% of
      children, and 14.7% of children had been revaccinated. Strong TST reactions were
      observed in 110/181 children. Seventy-six children (41.3%) were considered as
      infected by M. tuberculosis and 25 cases (13.6%) of TB were detected, of which
      seven (28%) were asymptomatic. There was greater occurrence of disease when the
      contact lived with more than one source of infection (p=0.02). CONCLUSIONS: The
      detection of TB disease and infection was high in the studied population. Contact
      control must be emphasized, for it allows for the diagnosis of TB in children who
      are still asymptomatic, in addition to identifying infected subjects who may
      profit from chemoprophylaxis.

PMID- 15243662
TI  - [Distribution of acute respiratory diseases in Brazil from 1996 to 2001, Brazil].
AB  - OBJECTIVE: Acute respiratory diseases -- ARD, mainly pneumonias, are the most
      important cause of death among children under five years of age and are
      responsible for severe diseases among people over sixty years of age. This study
      aims to describe the main epidemiological characteristics of ARD cases notified
      by healthcare centers. METHODS: ARD patients' records from medical consultations
      at 100 public health care centers and hospitals were reviewed every week in the
      period from 1996 to 2001 and data was filled out on a specific form. Data was
      classified as pneumonia and not pneumonia according to age groups. RESULTS:
      During this period, 2,050,845 ARD cases were informed. May and June were the
      months with the largest number of cases. ARDs were more frequent among children
      aged one to four years old. The latter concentrated about twice the number of
      cases of other age groups. Pneumonias represented approximately 7.7% of the ARD
      cases. CONCLUSIONS: The magnitude of ARD numbers may be observed and it should
      stimulate appropriate diagnosis, early treatment, and prevention, both in regard
      to the event itself and complications ensuing from it.

PMID- 15243663
TI  - [Use of an artificial neural network for detecting excess deaths due to cholera
      in Ceara, Brazil].
AB  - OBJECTIVE: To evaluate recurrent neural networks as a predictive technique for
      time-series in the health field. METHODS: The study was carried out during a
      cholera epidemic which took place in 1993 and 1994 in the state of Ceara,
      northeastern Brazil, and was based on excess deaths having 'poorly defined
      intestinal infections' as the underlying cause (ICD-9). The monthly number of
      deaths with due to this cause between 1979 and 1995 in the state of Ceara was
      obtained from the Ministry of Health's Mortality Information System (SIM). A
      network comprising two neurons in the input layer, twelve in the hidden layer,
      one in the output layer, and one in the memory layer was trained by
      backpropagation using the fist 150 observations, with 0.01 learning rate and 0.9
      momentum. Training was ended after 22,000 epochs. We compare the results with
      those of a negative binomial regression. RESULTS: ANN forecasting was adequate.
      Excessive mortality (number of deaths above the upper limit of the confidence
      interval) was detected in December 1993 and October/November 1994. However,
      negative binomial regression detected excess mortality from March 1992 onwards.
      CONCLUSIONS: The artificial neural network showed good predictive ability,
      especially in the initial period, and was able to detect alterations concomitant
      and a subsequent to the cholera epidemic. However, it was less precise that the
      binomial regression model, which was more sensitive to abnormal data concomitant
      with cholera circulation.

PMID- 15243664
TI  - [Use of drugs to treat respiratory tract infections in the community].
AB  - OBJECTIVE: This study describes the utilization of drugs to treat respiratory
      tract infections in a community setting. The description of antimicrobial and non
      antimicrobial drugs use is important to design interventions aimed at improving
      treatment strategies for these common illnesses. METHODS: In a population-based
      cross-sectional study, 6145 individuals living in an urban area in southern
      Brazil were inquired about the use of drugs for the treatment of respiratory
      tract infections in the 30 days previous to the interview. The Pearson chi-square
      test was used for statistical analyses. RESULTS: The global prevalence of
      respiratory infections treated with drugs was 6.3%. The prevalence was higher for
      children under 4 years of age (18%) and lower for the elderly (3%; p<0.001).
      Fifty-nine percent of the individuals used antimicrobials to treat respiratory
      infections. "Sore throat" was the main clinical condition associated with drug
      use (41%). Amoxicilin was the antimicrobial drug most frequently used (38%),
      while non-steroidal anti-inflamatory drugs were the most frequent among the non
      antimicrobial drugs (27%). CONCLUSIONS: Antimicrobials were used in nearly 60% of
      the respiratory tract infections treated with some drug, even though they are
      mostly viral in their origin. The indiscriminate use of these drugs not only
      raises the costs of treatments, but may also lead to the emergence of bacterial
      resistance against the antimicrobials.

PMID- 15243666
TI  - [Occurrence of hospital infection among interned elderly in a university
      hospital].
AB  - OBJECTIVE: Hospital infection is an important cause of morbidity and mortality in
      the elderly population. The objective of this study was to evaluate the
      occurrence of hospital infection and risk factors associated with it. METHODS:
      This is a prospective study of a sample of 332 elderly people, 60 years and
      older, interned in a university hospital, between September 1999 and February
      2000. Sample size was calculated according to the Fisher and Belle formula, with
      a confidence interval of 0.95%, from a total of 760 elderly patients interned, in
      proportion to the number of patients present in each in-patient unit, in the
      1997. Criteria for defining hospital infection were those established by the
      Center for Diseases and Prevention Control. Odds ratio and logistic regression
      were utilized for statistical analysis of the data. RESULTS: The rate of hospital
      infection was 23.6%. The prevalent topographies of infection were respiratory
      infections (27.6%), urinary tract infections (26.4%) and surgical wound
      infections (23.6%). The period of hospitalization of patients who did have
      hospital infections was 6.9 days, while those who had hospital infections were
      hospitalized for 15.9 days (p<0.05). Mortality rate among hospitalized patients
      was 9.6% and the rate of lethality among patients with hospital infection was
      22.9% (p<0.05). Risk factors found for hospital infection were cholangiography
      (odds ratio (OR) =46.4, confidence interval 95% (CI95%) =4.4-485); diabetes
      mellitus (OR=9.9, CI 95% =4.4-22.3); chronic obstructive pulmonary disease
      (OR=8.3, CI 95% =2.9-23.7); urinary catheters (OR=5, CI 95% =2.7-11.8);
      hospitalization with community infection (OR=3.9, CI 95% =1.7-8.9) and mechanic
      ventilation (OR=3.8, CI 95% =1.9-6.3). CONCLUSIONS: Hospital infection presented
      elevated incidence and lethality and it increased the period of hospitalization
      among the elderly studied.

PMID- 15243665
TI  - [Depressive symptoms and associated factors in an elderly population in southern
      Brazil].
AB  - OBJECTIVE: To determine the frequency of some depressive symptoms in the elderly,
      to build up a score of depressive symptoms and to evaluate the association
      between depressive symptoms and demographic, socioeconomic and behavioral
      variables. METHODS: A population-based cross-sectional study was conducted in
      individuals aged 60 and more living in the urban city area of Pelotas, Brazil.
      The sample was selected in multiple stages based on the city's census tracts. It
      was used a questionnaire comprising eight question commonly included in
      depression evaluation instruments and specific to the elderly. Analyses were
      carried out using multiple linear regressions following a hierarchical approach.
      RESULTS: A total of 583 subjects were interviewed and non-response rate was 4.7%.
      Each participant had on the average score of depressive symptoms was 3.4 (SD
      2.1)Lack of willingness to carry out daily activities was the most frequent
      symptom (73.9%) reported. In the adjusted analysis according to the conceptual
      framework, the following groups had statistically higher averages (p<0.05) of
      depressive symptoms: older women, individuals with less schooling, unemployed,
      smokers, and those whose family member or significant other died in the past
      year. CONCLUSIONS: It was found both high rates of isolated symptoms and high
      average of depressive symptoms in the study sample, highlighting the importance
      of studying specific symptoms of the elderly, which are different from those
      found in young adults.

PMID- 15243667
TI  - Trends in the modes of delivery and their impact on perinatal mortality rates.
AB  - OBJECTIVE: To determine changes in the incidence of vaginal deliveries, cesarean
      sections, and forceps deliveries and their potential association with fetal,
      early neonatal, and perinatal mortality rates over time. METHODS: A retrospective
      study was carried out and the occurrence of deliveries supervised by university
      services between January 1991 and December 2000 was determined. Data regarding
      fetal, early neonatal, and perinatal deaths were assessed using obstetric and
      pediatric records and autopsy reports. RESULTS: Of a total of 33,360 deliveries,
      the incidence of vaginal deliveries, cesarean sections, and forceps deliveries
      was relatively steady (around 60, 30, and 10%, respectively) while, at the same
      time, there was a marked reduction in fetal mortality (from 33.3 to 13.0 per
      thousand), early neonatal mortality (from 30.6 to 9.0 per thousand), and
      perinatal mortality (from 56.4 to 19.3 per thousand). CONCLUSIONS: The marked
      reduction in perinatal mortality rates seen during the study period without an
      increase in cesarean sections indicates that the decrease in perinatal mortality
      was not impacted by cesarean section rates. The plausible hypothesis seems to be
      that the reduction in perinatal mortality of deliveries performed under the
      supervision of university services was more likely to be associated with better
      neonatal care rather than the mode of delivery.

PMID- 15243668
TI  - [Quality of data on myocardial infarction deaths, Brazil].
AB  - OBJECTIVE: To evaluate the quality of data on acute myocardial infarction deaths
      from mortality information systems. METHODS: Data on in-hospital acute myocardial
      infarction mortality collected from database of the Mortality Information System
      (SIM) and Hospital Information System (SIH), in 2000, were analyzed. Then data
      collected from medical records from two hospitals affiliated to the Unified
      Health System (SUS) in Rio de Janeiro, Brazil, were also analyzed. Medical
      records, death certificates, and hospital admission forms (AIH) were compared
      using the World Health Organization criteria of acute myocardial infarction
      diagnosis. Agreement among different sources was analyzed using Cohen's Kappa
      statistics and intraclass correlation coefficient. RESULTS: In-hospital death
      registries in SIM are much larger than in SIH/SUS. There were identified three
      mechanisms that could explain most of the observed discrepancy: missing hospital
      admission forms (32.9%), different main diagnosis registered in SIH/SUS (19.2%),
      and under reporting of deaths in hospital admission forms (3.3%). The medical
      records review could confirm the diagnoses of acute myocardial infarction in
      67.1% of all deaths reported in death certificates. The sensitivity of data on
      acute myocardial infarction deaths in death certificates was about 90% for both
      health information systems analyzed. CONCLUSIONS: There is a need for actions to
      improve the quality of data registered in SIH/SUS such as standardization of
      criteria for issuing hospital admission forms during hospital emergencies and
      training local staff on registration systems.

PMID- 15243669
TI  - [Validity of self-reported weight and height and the body mass index within the
      "Pro-saude" study].
AB  - OBJECTIVE: Evaluate the validity of self-reported weight and height and the body
      mass index (BMI). METHODS: A study was made of 3,713 employees of a public
      university in Rio de Janeiro, in which they were participants in Phase 1 of a
      longitudinal study. Information was obtained through a self-administered
      questionnaire, and measurements were carried out after its application. Student's
      paired t-test, Bland & Altman's graphs and the intraclass correlation coefficient
      (ICC) were utilized to evaluate the differences between the measured and the
      reported parameters. The sensitivity and specificity of the various BMI
      categories were estimated. RESULTS: There was high agreement between the measured
      and reported weights (ICC=0.977) and heights (ICC=0.943). The BMI sensitivity, in
      its various categories, was around 80%, and the specificity was close to 92%.
      There was a slight and uniform tendency toward self-reported weight
      underestimation and self-reported height overestimation in both sexes.
      CONCLUSIONS: Self-reported and measured weight and height information had good
      agreement and validity. In similar populations, when few resources are available,
      it is possible to use self-reported data instead of actual measurements.

PMID- 15243670
TI  - [Lower extremity amputations in diabetic patients: a case-control study].
AB  - OBJECTIVE: Lower extremity amputation is an increasing problem among diabetic
      patients and an important public health problem. The study purpose was to
      identify factors associated with lower extremity amputation. METHODS: A matched
      case-control study was carried out among diabetic patients. Cases were selected
      in public health programs of the city of Sao Paulo, Brazil. One hundred and
      seventeen cases of diabetics with lower extremity amputation were compared to 234
      controls of diabetics without amputation, matched by sex, age, and duration of
      disease. Sociodemographic variables, life habits (smoking and alcohol drinking),
      clinical aspects, and health education in diabetes were included. Univariate
      analyses and conditional logistic regression method were applied to data.
      RESULTS: Data showed evidence of association for: smoking, last glucose test > or
      = 200 mg/dl, presence of peripheral somatic neuropathy and vibratory perception
      (tuning fork 128 Hz), and peripheral vascular disease. Diabetes treatment and
      attending nursing appointments for diabetes education were important factors for
      preventing lower extremity amputation in diabetic patients. CONCLUSIONS: The
      knowledge of determinants and intervening factors for this condition will lead to
      cost reduction and better quality of care delivered in public health services.

PMID- 15243671
TI  - [Social representations of the relationships between plant vases and the dengue
      vector].
AB  - OBJECTIVE: To investigate how houseplant 'caretakers' represent the relationship
      between plant vases and breeding sites for the dengue vector, in order to
      reformulate educational policies. METHODS: The present study was carried out
      among caretakers from three Sao Paulo State municipalities in which dengue is
      known to exist and in which extensive educational activities had been previously
      conducted. Twenty households from each of the municipalities studied were
      selected based on larval density evaluation bulletins elaborated by SUCEN
      (Endemic Disease Control Coordination) and classified as positive or negative for
      the presence of Aedes aegypti larvae in plant vases. The 60 participants were
      aged 20-65 years and were directly involved in plant care. Interviews were
      carried out using a semi-structured questionnaire, and recorded in cassette
      tapes. Data were tabulated using the collective subject discourse technique.
      RESULTS: Negative representations found included: erroneous information in the
      population's imaginary universe; disbelief that a 'tiny little mosquito' could
      cause such extensive problems; belief in the disease only after its concrete
      manifestation; and mistrust in educational activities in general. Positive
      representations included: understanding of the basic mechanism of dengue
      transmission; appreciation of the role and constant presence of sanitary
      authorities; understanding of their own share of responsibility in fighting the
      disease. CONCLUSIONS: With respect to vector control activities, the exceedingly
      synthetic messages emitted by the sanitary authorities prevent the information
      from being assimilated by the population to the desirable extent. Educational
      activities must be understood by the population to which they are destined if any
      behavioral changes are to take place.

PMID- 15243673
TI  - [The Baby-Friendly Hospital Initiative and breastfeeding in a neonatal unit].
AB  - OBJECTIVE: To evaluate the impact of the Baby-Friendly Hospital Initiative on
      breastfeeding practices among newborns admitted to a neonatal unit, during
      hospitalization and during the first six months of life. METHODS: The medical
      records of all newborns admitted to the neonatal unit of a teaching hospital in
      1994 (N=285) and 1998 (N=368) were reviewed, and information on the infants'
      feeding practices during hospitalization and during the first six months of life
      was analyzed. The duration of breastfeeding and exclusive breastfeeding and the
      differences between the two years were assessed using the Kaplan-Meier technique
      and the Log-Rank test. Logistic regression and Cox analysis were performed for
      confounder control. RESULTS: There was an important increase in the percentage of
      infants given breast milk exclusively (1.9% in 1994 to 41.7% in 1998) during
      hospitalization, and feeding with formula alone, observed in 17.7% of infants in
      1994, was no longer noted in 1998. With respect to breastfeeding practices during
      the first six months of life, the median duration of exclusive breastfeeding
      increased from 12 days in 1994 to 45 days in 1998. As to breastfeeding, which
      includes the ingestion of other types of food, no significant difference was
      observed. CONCLUSIONS: The implementation of the initiative in the studied
      hospital contributed towards an increase in the exclusive breastfeeding of
      newborn babies during neonatal unit admission and during the first six months of
      life.

PMID- 15243672
TI  - [Educational program in schistosomiasis: a model for a methodological approach].
AB  - OBJECTIVE: Lack of knowledge is one of the factors responsible for the
      persistence of infectious diseases in Brazil. This study had the objective of
      developing, implementing and evaluating a low-cost educational program using
      schistosomiasis patients as a model. METHODS: This was a descriptive study
      developed using a population of healthy people (group 1) and schistosomiasis
      patients (groups 2 and 3), with 20 individuals in each group. Teaching material
      (illustrated manual and album of leaflets) and a questionnaire consisting of 17
      questions to evaluate the groups' knowledge were devised. The questionnaire was
      applied to groups 1 and 2 before and to group 3 after the educational program.
      The variables studied were the educational program, level of schooling, age,
      clinical form of schistosomiasis, symptoms, and the subject's performance when
      answering the questionnaire. For the statistical analysis, Fisher's exact test
      and variance analysis with one fixed factor were utilized. RESULTS: The
      educational program was evaluated in the form of four topics: cycle, clinical
      presentation, treatment and prevention of the disease. The median number of
      correct responses to the questionnaire was higher for group 3 than for groups 1
      and 2, for all the topics dealt with. This median was also higher for group 2
      than for group 1, for all topics except for the item "prevention". CONCLUSIONS:
      The educational process applied was efficient and improved the knowledge of the
      disease. It may provide an effective low-cost methodological model that can also
      be applied to combating other endemic diseases.

PMID- 15243674
TI  - [Pharmacists' knowledge of sanitary legislation and professional regulations].
AB  - OBJECTIVE: To characterize the profile of pharmacists employed as technical
      supervisors in drugstores and evaluate their knowledge regarding certain aspects
      of the legislation controlling drugstores and the profession in general. METHODS:
      Based on 175 drugstores in the city of Ribeirao Preto, southeastern Brazil, 100
      pharmacists/technical supervisors were randomly selected. Data collection was
      done by means of in-person interviews, and was guided by a questionnaire
      evaluating knowledge and attitudes. Data were processed and analyzed using Epi
      Info and Stata software. Associations were sought between dependent and
      independent variables using Pearson's chi-squared and Fisher's exact tests.
      RESULTS: Most pharmacists were women (64%), aged 22-29 years (47%), graduated
      approximately three years prior to data collection, trained to work in the
      pharmaceutical industry (36%) or in clinical analysis (29%). Pharmacist's
      knowledge of sanitary legislation was considered as insufficient for 28% of
      subjects, regular for 50%, and good for 22%. Low levels of knowledge were
      observed regarding the legal requirement for the presence of a pharmacist during
      the entire drugstore opening hours, pharmacists' attributions, sale of
      antibiotics, and penicillin administration. It was found that most professionals
      have difficulties handling the concepts of 'generic' and 'similar' drugs. Low
      level of knowledge was not associated with any of the independent variables,
      indicating that this is a generalized phenomenon, i.e., one present among
      pharmacists of all age groups and both sexes, irrespective of the time since
      graduation, institution attended, and modality of graduation, among others.
      CONCLUSIONS: We conclude that training in the field of drug pharmaceutical care,
      during undergraduate studies and, especially, during traineeship in pharmacies
      and drugstores is deficient. It is necessary to divulge information concerning
      sanitary legislation so that pharmacists may fully exert their profession,
      without risk of legal threats or hazard to the population.

PMID- 15243675
TI  - [Validation of the "International Consultation on Incontinence Questionnaire --
      Short Form" (ICIQ-SF) for Portuguese].
AB  - OBJECTIVE: To translate into and validate for Portuguese the "International
      Consultation on Incontinence Questionnaire -- Short Form" (ICIQ-SF), a condition
      specific quality-of-life questionnaire for patients with urinary incontinence.
      METHODS: Two Brazilians independently translated the original ICIQ-SF into
      Portuguese. These two translations were harmonized, and then checked by
      independent back-translation by two native English speakers. The harmonized
      translation was pre-tested in a pilot study on 20 patients. The final version of
      the ICIQ-SF in Portuguese was applied to 123 consecutive patients aged 16 or over
      (29 males and 94 females) with a complaint of urinary incontinence, who had
      sought the Department of Urogynecology and Uroneurology of the School of Medical
      Sciences of Unicamp. The Portuguese version of the King's Health Questionnaire
      (KHQ) was also applied to the same group. The psychometric properties of the
      questionnaire, such as reliability and construct validity were assessed. RESULTS:
      The median age was 53 years (range: 16 to 86). The mean retest interval for the
      ICIQ-SF was 14.37 days (range: 6 to 41). No changes from the original format of
      the ICIQ-SF were observed at the end of the process of translation and cultural
      adaptation. The internal consistency was high (0.88), as measured by the Cronbach
      alpha coefficient. The test-retest value was considered moderate to strong, as
      measured by the weighted Kappa index (range: 0.72 to 0.75) and Pearson
      correlation coefficient (0.89). The correlation between the ICIQ-SF and KHQ was
      considered to be moderate to good for most items (range: 0.44 to 0.77). The
      evaluation of the construct and concurrent validity was also satisfactory and
      statistically significant. CONCLUSIONS: The "International Consultation on
      Incontinence Questionnaire" (ICIQ-SF) was successfully translated into Portuguese
      and validated for application to Brazilian female and male patients complaining
      of urinary incontinence, with satisfactory reliability and construct validity.

PMID- 15243676
TI  - [Psycometrics properties of subjetive indicator in children].
AB  - OBJECTIVE: To evaluate the psychometric properties of the Oral Heath Impact
      Profile (OHIP-14) to measure oral health in children. METHODS: The OHIP-14
      questionnaire was applied to 312 schoolchildren aged 12 years residing in Sabara,
      Brazil, in 2001. OHIP-14's reliability was evaluated using Cronbach's alpha and
      correlation intraclass coefficient. For examining content validity, Pearson's
      correlation and logistic regression analysis were applied. For construct
      validity, Student's t-test and Tukey-Kramer test were used. RESULTS: Tooth loss
      among the subjects was low in this study (between 85% and 100%). Caries
      prevalence was very low and not detectable in 59.0% of the sample. The logistic
      regression model showed high predictive values for reporting treatment need and
      intermediate values for dental caries perception. The comparison between
      different OHIP average scores, according to the DMF-S index's three categories of
      decayed, missing, filled surfaces, indicated significant difference only for the
      categories social disability and deficit. CONCLUSIONS: The study results
      indicated that the adolescents did not report high prevalence of oral conditions.
      The OHIP was associated with perceived treatment need, reporting of dental caries
      and increased DMF-S index. These results suggest that the OHIP has good
      psychometric properties when applied to children and could be a promising
      instrument for screening priority care groups.

PMID- 15243677
TI  - [Dental pain as the reason for visiting a dentist in a Brazilian adult
      population].
AB  - OBJECTIVE: The occurrence of orofacial pain and chronic pain are frequent
      subjects for study today, but few studies have been made on dental pain in
      Brazil. The objective of the study was to assess the prevalence of dental pain
      and the associated factors as the reason for visiting a dentist among adults.
      METHODS: A cross-sectional study was carried out among 860 workers aged 18-58
      years at a cooperative located in the State of Santa Catarina, in 1999. The
      clinical examinations and interviews were carried out by dentists who had
      received prior guidance. Complaints of dental pain as the reason for the last
      visit to a dentist were analyzed as the dependent variable, in relation to the
      socioeconomic and demographic conditions, access to dental services, shift
      pattern and caries (via the DMFT index), as the independent variables. Non
      conditional multiple logistic regression analysis was utilized. RESULTS: The
      prevalence of dental pain as the reason for the last visit to a dentist was 18.7%
      (CI 95%: 15.9-20.1) and the mean DMFT index (decayed, missing and filled teeth)
      was 20.2 (CI 95%: 19.7-20.7), with 54% represented by the 'missing' component.
      The following were independently associated with the presence of dental pain:
      schooling of less than or equal to eight years (OR=1.9; CI 95%: 1.1-3.1); four to
      fifteen teeth lost due to caries (OR=2.6; CI 95%: 1.4-4.9); 16 to 32 teeth lost
      due to caries (OR=2.5; CI 95%: 1.1-5.8); and not having visited the company's
      dental service (OR=2.8; CI 95%: 1.6-5.1). CONCLUSIONS: Dental pain reflects the
      severity of the dental caries, expressed by the 'missing' component of the DMFT
      and non-usage of the company's dental services. These factors are determined by
      social conditions and represented by the schooling level.

PMID- 15243678
TI  - [Evaluation of the fluoride concentration and consumption of mineral water].
AB  - OBJECTIVE: Considering that water is an importance source of fluoride intake, and
      that the consumption of mineral water and prevalence of dental fluorosis have
      been increasing, the aim of this study was to evaluate the consumption of mineral
      water and its fluoride concentration. METHODS: The study was performed in
      residential districts of the municipality of Bauru, State of Sao Paulo, by means
      of stratified sampling via clusters. Each cluster corresponded to one residential
      block. For randomization purposes, the residential blocks were numbered within
      the 17 districts established by the city plan. One thousand homes were thus
      visited. Mineral water samples were collected using previously labeled 50 ml
      plastic flasks. Fluoride analysis was done using an ion-sensitive electrode
      (Orion 9609), after buffering using TISAB II. Information on the consumption of
      mineral water was obtained by means of applying a questionnaire. RESULTS: Around
      29.72% of the city's population was consuming mineral water. In the 260 samples
      analyzed from 29 different brands of water, the fluoride concentration ranged
      from 0.045 to 1.515 mg/l. For one brand, the label stated that the fluoride
      concentration was 0.220 mg/l, but analysis revealed a concentration of 1.515
      mg/l. Moreover, some brands did not specify the fluoride concentration on the
      label and, for these, the analysis showed concentrations ranging from 0.049 to
      0.924 mg/l. CONCLUSIONS: The results demonstrated wide variation in fluoride
      concentrations and reinforce the importance of the control of such waters by the
      sanitary surveillance agency.

PMID- 15243679
TI  - [Mortality profile of female Rhodnius robustus (Heteroptera: Reduviidae)].
AB  - Mortality profile of 48 adult females of Rhodnius robustus shows that data
      analyzed by weeks and days have a statistical significantly fit (p<0.0001), that
      allows to affirm that mortality of this species is Gompertzian.

PMID- 15243680
TI  - Cryptosporidiosis occurrence in HIV+ patients attended in a hospital, Brazil.
AB  - Cryptosporidiosis occurrence was determined in HIV+ patient assisted in the
      Clinic of Infect-parasitic Diseases in a hospital of Nova Iguacu, Rio de Janeiro,
      Brazil, in the period from July/1998 to March/1999. In order to research, seventy
      five patient, carriers of diarrhea or not, were appraised. The samples of feces
      were collected and placed in saline solution with formaldehyde (5%). The Modified
      Ritchie technique was used for the oocysts research, and the smears were stained
      with Safranine O methylene blue. The results verified 9.33% of positive samples,
      with higher frequency of cases in patients of the masculine sex from 20 to 50
      years old, however without significant difference.

PMID- 15243681
TI  - [Implementation of workers' health program in the SUS/SP].

PMID- 15243682
TI  - [Anvisa enhances infection control in health services].

PMID- 15243683
TI  - (+)-discodermolide: a marine natural product against cancer.
AB  - (+)-discodermolide was isolated in 1990 by Gunasekera et al. from the deep-water
      Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way
      to the successful cancer drug Taxol that has become the best-selling anticancer
      drug in history. Taxol is also the first natural product described that
      stabilizes the microtubules involved in many aspects of cellular biology and that
      represent an important target of anticancer chemotherapeutics. However, (+)
      discodermolide appears to be far more potent than Taxol against tumors that have
      developed multiple-drug resistance, with an IC50 in the low nanomolar range. Due
      to these excellent results, this natural product was licensed to Novartis
      Pharmaceutical Corporation in early 1998. The present review covers the history,
      biological activity, total synthesis, and synthetic analogs of (+)
      discodermolide.

PMID- 15243684
TI  - Intracranial pressure. Part one: historical overview and basic concepts.

PMID- 15243685
TI  - Intracranial pressure. Part two: Clinical applications and technology.

PMID- 15243687
TI  - Length of stay and antipsychotic treatment costs of patients with acute psychosis
      admitted to hospital in Spain. Description and associated factors. The Psychosp
      study.
AB  - OBJECTIVE: The aim of this study was to describe the length of stay, cost of drug
      treatment, diagnostic tests and other therapeutic measures in acute psychotic
      patients admitted to acute in-patient psychiatric units and to analyse the
      factors associated with these. METHODS: A retrospective review was made of
      medical records of 200 patients admitted for acute psychosis in eight Spanish
      hospitals. Information was collected concerning the length of stay, cost of drug
      treatment and diagnostic tests; bivariate and multivariate analysis was made of
      factors associated with length of stay and cost of antipsychotic drug treatment.
      RESULTS: The average admission cost ranged between 2,830.29 and 3,624.95 euros,
      with a wide variability among hospitals. Of this cost, 94.3% corresponded to
      fixed costs, 3.4% to diagnostic tests and 2.4% to drug treatment (84.2% of this
      latter cost corresponded to antipsychotic drugs). Age younger than 25 years and a
      diagnosis of schizophrenia were associated with longer hospital stays; longer
      length of stay, the presence of aggressiveness/agitation, a diagnosis of
      schizophrenia, age younger than 25 years and the use of atypical antipsychotics
      were associated with higher costs in antipsychotic drug treatment. CONCLUSIONS:
      The hospital admission cost of an acute psychotic episode is mostly dependent on
      the structural costs derived from in-patient treatment. The differences in costs
      seem to be related to the different length of stay schemes used by the various
      hospitals rather than to the clinical characteristics of patients or the drugs
      used.

PMID- 15243686
TI  - Patterns of colonization by Pseudomonas aeruginosa in intubated patients: a 3
      year prospective study of 1,607 isolates using pulsed-field gel electrophoresis
      with implications for prevention of ventilator-associated pneumonia.
AB  - OBJECTIVE: To identify routes and patterns of colonization with Pseudomonas
      aeruginosa in intubated patients to design strategies of prevention for
      respiratory infection. DESIGN AND SETTING: Prospective and observational study in
      the 16-bed intensive care unit of a teaching hospital. PATIENTS AND PARTICIPANTS:
      Ninety-eight intubated patients were investigated over a 3-year period. Those
      ventilated less than 72 h were excluded. MEASUREMENTS AND RESULTS: Samples from
      the tap water from each patient's room, stomach, oropharynx, subglottic
      secretions, trachea, and rectum were collected when the patient was intubated,
      and then three times per week. Pulsed-field gel electrophoresis was performed to
      type the strains. We identified 1,607 isolates pertaining to 35 different
      pulsotypes. Overall 54.2% of patients presented colonization, and tracheal
      colonization was present in 30.5%. Ten patients had colonization at intubation,
      and four of these developed ventilator-associated pneumonia (VAP) after a mean of
      4+/-2 days. ICU-acquired colonization occurred in 31 patients, and 4 of these
      developed VAP after a median of 10+/-5 days. P. aeruginosa was isolated from the
      room's tap water in 62.4% of samples. More than 90% of tap water samples had
      pulsotypes 1 and 2, which were frequently isolated in the stomach (59%) but were
      only rarely associated with VAP. CONCLUSIONS: Although colonization/infection
      with P. aeruginosa in intubated patients tends to be endogenous, exogenous
      sources should not be ruled out. A combination of early identification (and
      eradication) of airways colonization by P. aeruginosa plus infection control
      measures targeted to reduce cross-contamination should be the basis to prevent
      pulmonary infection.

PMID- 15243688
TI  - Associations between visual and auditory hallucinations in children and
      adolescents, and tobacco use in adulthood.
AB  - AIMS: The cross-sectional association between tobacco use and psychotic features
      has been well established. If psychotic features precede tobacco use, then
      tobacco may be used to self-medicate psychotic symptoms. The aim was to assess if
      psychotic features in adolescents constitute a risk factor for later tobacco use.
      DESIGN: A random target sample of 2,600 children aged 4-16 years from the Dutch
      general population was followed up across a 14-year interval. At different ages
      (childhood, adolescence, young adulthood), information about visual and auditory
      hallucinations was obtained using standardized questionnaires for parents and
      subjects themselves. At outcome (ages 18-30), tobacco use was assessed. FINDINGS:
      Auditory hallucinations, but not visual hallucinations, in early and late
      adolescence, assessed via parents and adolescents themselves, predicted tobacco
      use in adulthood. CONCLUSIONS: The present study confirmed that auditory
      psychotic features in adolescence are associated with tobacco use in adulthood.
      Tobacco may be used to self-medicate auditory, but not visual, hallucinations.

PMID- 15243689
TI  - Negative and positive participant responses to the Composite International
      Diagnostic Interview. Results of the Netherlands Mental Health Survey and
      Incidence Study.
AB  - BACKGROUND: Little is known about the emotional responses of participants in
      community surveys to standardised psychiatric interviews like the Composite
      International Diagnostic Interview (CIDI). This study investigates the proportion
      of subjects responding negatively or positively to the CIDI, and identifies their
      sociodemographic, psychopathological, personality and social characteristics.
      METHODS: At the end of the three-wave Netherlands Mental Health Survey and
      Incidence Study, 4796 participants aged 18-64 at baseline were questioned about
      how the interviews had affected them. RESULTS: In all, 2.7% found the interviews
      quite distressing and 9.5% somewhat distressing. Compared to those without
      distress, they were more likely to be female, not living with a partner, not in
      paid employment, and to have a somatic disorder. A total of 5.7% of subjects
      reported that participation had helped them cope better with problems, and 3.4%
      reported they could now seek help more easily. These were more likely to be
      older, less educated, not in paid employment (except those seeking help more
      easily) and to have a somatic disorder. Both negative and positive responses were
      associated with mood, anxiety and substance use disorders and comorbidity, as
      well as with neuroticism, external mastery, low self-esteem and low social
      support. CONCLUSION: Only a small minority of participants reported distress from
      the interviews. This is an important finding for ethics committees charged with
      approving general population surveys that use the CIDI. It can also be valuable
      for planning such studies, enabling researchers to inform participants more fully
      about the effects of the interview before asking them for informed consent.

PMID- 15243690
TI  - Burden in adolescent children of parents with schizophrenia. The Edmonton High
      Risk Project.
AB  - OBJECTIVE: Adolescent children of parents with schizophrenia are generally
      overlooked in studies of family burden. Few published data exist about this
      younger cohort compared to adult family members such as parents, spouses, and
      siblings. This pilot study aims to examine the types of burden described by
      adolescent children of parents with a diagnosis of schizophrenia. METHODS:
      Thirteen adolescents (9F: 4M) between the ages of 13 and 18 who had at least one
      parent diagnosed with schizophrenia were administered a semi-structured interview
      as part of a pilot project to examine burden in this group. Questions asked
      during the interview were directed at the subject's knowledge of the disorder,
      relationship with the parent, impact of the disorder on personal life, coping
      strategies used, and future concerns. RESULTS: Responses showed that the
      adolescents were uninformed about their parent's illness, had difficulties
      dealing with symptoms (positive and negative), were required to assume additional
      household responsibilities, and were concerned about their parent's future
      welfare. CONCLUSION: This pilot study illustrates that children of individuals
      with schizophrenia feel their lives are impacted by their parent's illness. More
      research is needed in this area to quantify and describe the types of burden
      experienced by this vulnerable group to ensure availability of adequate support.

PMID- 15243691
TI  - The effects of religious versus secular education on suicide ideation and
      suicidal attitudes in adolescents in Turkey.
AB  - BACKGROUND: Religion is associated with lower rates of self-killing, but the
      mechanism underlying religion-suicide association is not clear. To better
      understand this relationship, the present study investigated the impact of
      religious versus secular education on suicidal ideation and attitudes towards
      suicide and a suicidal close friend in Turkish adolescents. Deduced from
      religious commitment, social integration, networking and stigma perspectives, the
      study tested five specific predictions. METHOD: A questionnaire was used to
      collect the data in a group of adolescents (n = 206) undergoing religious
      education and a group of adolescents (n = 214) undergoing secular education (N =
      420). RESULTS: Suicide ideation was more frequent in adolescents undergoing
      secular education than in those undergoing religious education. The secular group
      was more accepting of suicide than the religious group. Those from the religious
      group, however, were more accepting of a suicidal close friend than their secular
      counterparts. CONCLUSION: It seems that self-killing finds accepting attitudes in
      secular segments of societies and,hence, people consider self-killing as an
      option during times of personal crises. People from religious communities,
      however, seem not to accept self-killing as an option, but they are more positive
      toward persons who have considered suicide for one reason or another.

PMID- 15243692
TI  - Lay theories of schizophrenia. A cross-cultural comparison of British and Hong
      Kong Chinese attitudes, attributions and beliefs.
AB  - BACKGROUND: This study set out to compare British and Chinese young people's
      beliefs about the manifestations, causes and cures of schizophrenia. METHOD: A
      total of 339 participants completed a 60-item questionnaire to compare lay
      theories of schizophrenia between British (in England) and Chinese (in Hong Kong)
      participants. The participants completed the three-part questionnaire in their
      mother tongue looking at beliefs about schizophrenia in general, causal
      explanation for the aetiology of schizophrenia and optimal cures for the
      condition. It was hypothesized that the Chinese would possess more negative
      attitudes and beliefs about schizophrenia than the British. It was also predicted
      that the Chinese would tend to use primarily a sociological model to explain the
      aetiology of schizophrenia. RESULTS: These two hypotheses were confirmed after
      factor-analysing the internal structure of the three sections of the
      questionnaire. However, the Chinese, compared to the British, did not use more
      superstitious beliefs to explain the behaviour of people with schizophrenia.
      CONCLUSION: Concern with mental health literacy has led to more studies on lay
      theories about major mental illnesses (specifically schizophrenia) because these
      theories reflect societal attitudes to patients and behaviour toward them. This
      study suggests that even well-educated young people remain ignorant about one of
      the most challenging mental illnesses. Implications for help-seeking behaviour
      and the course of the illness in individuals are considered.

PMID- 15243693
TI  - Economic implications of shared care arrangements. A primary care based study of
      patients in an inner city sample.
AB  - BACKGROUND: Providing care for people with serious and enduring mental health
      problems has been prioritised in a number of countries. It has been recognised
      that good liaison between primary and secondary care services is required for
      care to be effective. However, little is known about the resource implications of
      different levels of 'shared care'. The aim of this study is to compare service
      use and costs of different levels of shared care between primary and secondary
      care services. METHOD: Service use data were collected at baseline and one year
      later for participants with severe mental illness and costs were calculated.
      Levels of shared care were categorised into low, medium and high tertiles.
      Comparisons were made between the groups using multivariate analysis to control
      for participant characteristics. RESULTS: Participants receiving a low level of
      shared care used residential care less and were less likely to have contacts with
      a psychiatrist or social worker than those receiving medium or high levels of
      shared care. Mean costs for a low level of shared care were significantly lower
      than for a medium level (a difference of pound 2606, 90% CI pound 452 to pound
      4923), but not significantly lower than for a high level of shared care
      (difference of pound 1867, 90% CI- pound 287 to pound 3903). CONCLUSION:
      Different levels of shared care are associated with different patterns of service
      use, with greater resource consumption associated with a medium level of shared
      care. Further work is required to investigate the causal links between integrated
      care and service use and costs.

PMID- 15243694
TI  - Psychiatric hospitalization and continuity of care in immigrants treated in
      Madrid (Spain).
AB  - BACKGROUND: The ethnic group and also the socioeconomic level of a patient are
      linked with the quality of the health care received that is associated, among
      other factors, with the continuity of care between the different services
      involved in treatment. The main goal of this study is to identify whether
      foreigners resident in Madrid run a greater risk than Spaniards of interruption
      in the continuity of their care after discharge from a psychiatric
      hospitalization. Other characteristics of the patients associated with disruption
      of care continuity are identified in order to be able to design specific actions
      with this group of subjects to foster their compliance with treatment. METHODS:
      An observational, prospective, controlled study is performed to analyse the risk
      of not attending the first outpatient appointment after discharge from hospital
      in 60 foreign patients versus 115 Spaniards admitted to four short-stay
      psychiatric hospitalization units in Madrid. RESULTS: The multivariate analysis
      indicates that the relevant factors associated with a break in the continuity of
      care are the fact of being an immigrant having a monthly income of less than 240
      <euro> [adjusted OR = 8.05 (2.59-25.05)], not having consulted with a mental
      health problem in the 6 months prior to admission [adjusted OR = 5.32 (1.84
      15.34)], the lack of collaboration with treatment by the family [adjusted OR =
      3.73 (1.33-10.42)] and suffering a personality disorder as the main diagnosis for
      admission [adjusted OR = 7.09 (1.26-39.98)], whereas the longer duration of the
      admission protects against the failure to attend the appointment after discharge
      [adjusted OR = 0.94 (0.90-0.99)]. CONCLUSIONS: While it is true that the results
      confirm the suspicion that the fact of being an immigrant hinders continuity of
      care in patients admitted to psychiatric hospitalization units in our community,
      this would not be the variable directly influencing the interruption of
      treatment, but rather a series of factors that are more likely to be associated
      with this group than with the native population. These variables are the ones
      that should alert us to the need for closer follow-up in the transfer of these
      patients from one mental health service to another.

PMID- 15243695
TI  - Mental health, burnout and job satisfaction among professionals in sheltered
      living in Flanders. A pilot study.
AB  - BACKGROUND: Interest has been growing over the last few years in the working
      conditions of professionals who deal with clients with severe and chronic mental
      illnesses. In this study, the relationship between the affective climate, as
      measured by the construct of expressed emotion, and professionals' feelings of
      well-being and burnout was investigated. It was hypothesised that high expressed
      emotion (EE) (= a high amount of criticism, hostility or emotional
      overinvolvement) would be related to high burnout scores. METHODS: Fifty-six
      professionals were interviewed about their schizophrenic clients who resided in
      sheltered-living houses in Flanders. EE was measured with two instruments, the
      Camberwell Family Interview (CFI) and the Perceived Criticism Scale (PCS). The
      professionals' characteristics were mental health (Symptom Checklist, SCL-90),
      job satisfaction (VEVAK), and burnout (a Dutch version of the Maslach Burnout
      Inventory, UBOS-C). RESULTS: Little indication was found for an association
      between EE and working conditions as measured with the CFI. For the PCS, a
      significant relationship was found between the resident version of the PCS and
      burnout. The professionals who were perceived by the residents as being very
      critical were less depersonalised and less emotionally exhausted than those who
      were not so perceived. CONCLUSIONS: High EE relationships can exist without
      feelings of stress and burnout.

PMID- 15243696
TI  - Work environment and job satisfaction. A psychometric evaluation of the Working
      Environment Scale-10.
AB  - BACKGROUND: The working environment in mental health wards has been shown to have
      profound effects on the health and work stability of mental health workers.
      Despite an apparent need for regular measurement of work environment, development
      of short and reliable instruments for such measurements has been largely
      neglected. The aim of the present study was to evaluate the psychometric
      properties of the Working Environment Scale-10 (WES-10). METHODS: During the
      period 1990 through 2000, a total of 640 staff members on 42 wards for psychotic
      patients completed the WES-10. To establish the number of subscales, a factor
      analysis was carried out. The internal consistency of the subscales was
      calculated as Cronbach's alpha. We also collected data concerning satisfaction
      with the ward, its patients and staff, and for how long the respondents had
      worked and expected to continue to work at the ward. RESULTS: We identified four
      subscales named: Self Realization, Workload, Conflict and Nervousness. The
      psychometric properties of the subscales proved to be acceptable. All the
      subscales were significantly correlated with at least one satisfaction item,
      and/or the time the staff expected to continue at the ward. Most notably, the
      Self Realization subscale was strongly correlated to general satisfaction with
      the ward, and to the time the staff expected to work on the ward in the future,
      while Conflict was strongly negatively correlated with liking for staff.
      CONCLUSION: The WES-10 appears to measure four clinically meaningful subscales.
      It seems well suited for use in further research and for evaluation of clinical
      milieus.

PMID- 15243698
TI  - Depressive symptoms amongst adolescent primary care attenders. Levels and
      associations.
AB  - BACKGROUND: Background High rates of depressive disorder have been documented
      amongst adolescents attending general practitioners (GPs) in urban areas.
      However, little is known about the associations of adolescent depression in
      primary care. METHOD: We completed a cross-sectional questionnaire survey of
      adolescents, their parents and general practitioners, following adolescent
      attendance at the surgery. RESULTS: We found high levels of depressive symptoms
      to be present in adolescent attenders of a broad range of social backgrounds.
      Depressive symptoms were associated with the following demographic and contextual
      factors: older age, female gender and parental psychiatric symptoms. They were
      also associated with the presence of physical symptoms causing psychosocial
      impairment, with health risks (use of cannabis and exposure to drugs) and with
      use of services (both primary care and mental health services). Levels of
      depressive symptoms were similar in urban and suburban groups. However,
      associations of depressive symptoms with smoking, exposure to drugs, cannabis use
      and primary care attendance were demonstrated in the suburban group and not the
      urban group. CONCLUSION: Adolescent GP attenders have high levels of depressive
      symptomatology. GP recognition and intervention should have the potential to
      impact on adolescent depression and on associated risks.

PMID- 15243697
TI  - Social exclusion in clients with comorbid mental health and substance misuse
      problems.
AB  - BACKGROUND: The concept of comorbid mental health problems and substance misuse
      has gained prominence in the last two decades, due in part to the closure of
      large psychiatric hospitals and to the increasing prevalence of drug use in the
      community. This client group has a dual requirement for both medical and social
      care needs and is at risk for social exclusion. METHODS: A retrospective matched
      case-control study to examine aspects of social exclusion between service users
      who have comorbid diagnoses and those with a single diagnosis. Samples were drawn
      from the service users of a mental health Trust in the South-East of England,
      from both Adult Mental Health (n = 400) and Drug and Alcohol services (n = 190).
      Data were collected from Care Programme Approach assessment forms and medical
      records. McNemar's chi(2) and odds ratios via a conditional logit regression
      model are used to test for differences in the social exclusion indicators.
      RESULTS: There were significant differences in social exclusion between the
      comorbid and singly diagnosed clients of the Adult Mental Health service, but
      differences were less pronounced between the comorbid and singly diagnosed
      clients of the specialist Drug and Alcohol service. CONCLUSIONS: Recent
      Government policy advocates treating comorbid clients within mainstream mental
      health services. Health care workers need to recognise the likelihood of high
      levels of social exclusion among clients with comorbid problems.

PMID- 15243700
TI  - Mutation at position -132 in the islet amyloid polypeptide ( IAPP) gene promoter
      enhances basal transcriptional activity through a new CRE-like binding site.
AB  - AIMS/HYPOTHESIS: Mutations in the islet amyloid polypeptide ( IAPP) gene may play
      a potential role in the abnormal regulation or expression of the peptide. The aim
      of this study was to determine the functional role of the -132 G/A mutation
      reported in the promoter region of the IAPP gene in a population of Spanish Type
      2 diabetic patients. METHODS: We investigated the transcriptional activity using
      MIN6 cells and luciferase reporter plasmids in several culture conditions. Key
      regulatory elements of the IAPP promoter region were also analysed by
      electrophoretic mobility shift assays (EMSA). RESULTS: The mutant construct
      doubled IAPP transcriptional activity ( p<0.001). Both constructs showed severely
      reduced promoter activity (four-fold decrease) in the presence of verapamil and
      diazoxide. In contrast, IAPP promoter activity was doubled after incubation with
      forskolin or dexamethasone, regardless of the glucose concentrations in the
      culture media. EMSA revealed that the -132 G/A mutation increased the binding
      affinity through two DNA-protein complexes. In addition, a cAMP-responsive
      element binding protein (CREB) was identified by super-shift EMSA.
      CONCLUSIONS/INTERPRETATION: Our studies show that the wild-type and the mutant
      constructs are regulated in a similar pattern under all conditions, strongly
      indicating that the -132 G/A mutation increases basal but not inducible
      transcription. These results may be explained by new binding to the mutant region
      through CREB and other transcription factors not yet identified.

PMID- 15243701
TI  - T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes
      that involves the abrupt onset of insulin-deficient hyperglycaemia. This subtype
      appears to be non-autoimmune because of the absence of diabetes-related
      autoantibodies in the serum, and of insulitis in pancreatic biopsy specimens. The
      pathogenesis of the disease is still unknown. In this study, we investigated
      whether T cell autoimmune responses are involved in fulminant Type 1 diabetes.
      METHODS: Cellular immune responses to beta cell autoantigens were studied by
      enzyme-linked immunospot (ELISPOT) assay in 13 fulminant Type 1 diabetic patients
      and 49 autoantibody-positive autoimmune Type 1 diabetic patients. Results were
      compared with those of 18 Type 2 diabetic patients, six secondary diabetic
      patients (diabetes due to chronic pancreatitis) and 35 healthy controls. RESULTS:
      Nine of 13 (69.2%) GAD-reactive Th1 cells, and three of 12 (25%) insulin-B9-23
      reactive Th1 cells were identified in fulminant Type 1 diabetic patients by
      ELISPOT, as in autoantibody-positive Type 1 diabetic patients. Four fulminant
      Type 1 diabetic patients possessed the highly diabetes-resistant allele DR2,
      three of whom had GAD-reactive Th1 cells in the periphery.
      CONCLUSIONS/INTERPRETATION: Peripheral immune reaction was observed in 69.2% of
      fulminant Type 1 diabetic patients, indicating that autoreactive T cells might
      contribute, at least in part, to the development of fulminant Type 1 diabetes.

PMID- 15243702
TI  - Ultrastructural alterations in capillaries of the diabetic hypertensive rat
      retina: protective effects of ACE inhibition.
AB  - AIMS/HYPOTHESIS: The ACE inhibitor cilazapril was administered to diabetic
      hypertensive rats to evaluate its ability to influence the development of retinal
      capillary alterations. METHODS: Normotensive (strain: Wistar Kyoto) and
      genetically hypertensive (strain: spontaneously hypertensive) rats were rendered
      diabetic by intravenous injections of streptozotocin. Half of the diabetic
      animals received cilazapril with their daily food. At 20 weeks of diabetes,
      endothelial cells, pericytes and extracellular matrix were assessed by
      ultrastructural morphometry. Each experimental group consisted of seven animals.
      RESULTS: Cilazapril normalised systolic arterial pressure in diabetic
      hypertensive rats (137+/-2 mm Hg compared with 188+/-16 mm Hg in non-medicated
      diabetic hypertensive rats, p<0.001). The number of endothelial intercellular
      junctions was reduced in untreated diabetic hypertensive rats (0.15+/-0.05,
      p<0.02, vs 0.47+/-0.20 in non-diabetic normotensive rats). In diabetic
      hypertensive animals treated with cilazapril, this loss was attenuated (0.32+/
      0.16, p<0.05). The significant thickening of the basement membrane observed in
      the diabetic normotensive (132.8+/-19.4 nm) and diabetic hypertensive (150.3+/
      20.2 nm) groups was decreased by cilazapril in the diabetic hypertensive group
      (116.7+/-11.0 nm, p<0.01), but was unaffected in the normotensive (131.9+/-17.3
      nm) group. No protective effect of the drug was observed in either group on
      pericytes. CONCLUSIONS/INTERPRETATION: Long-term administration of an effective
      antihypertensive therapy normalises endothelial alterations and basement membrane
      thickness in diabetic hypertensive conditions, and thus may account for the well
      known improvement of the blood-retinal barrier observed during antihypertensive
      treatment.

PMID- 15243703
TI  - Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition
      in the liver.
AB  - AIMS/HYPOTHESIS: We investigated the effect of elevated circulating NEFA on
      insulin-mediated hepatic glucose uptake (HGU) and whole-body glucose disposal (M)
      in eight healthy male subjects. METHODS: Studies were performed using positron
      emission tomography (PET) and [(18)F]-2-fluoro-2-deoxyglucose ([(18)F]FDG) during
      euglycaemic hyperinsulinaemia (0-120 min) and an Intralipid/heparin infusion
      (IL/Hep; -90-120 min). On a different day, similar measurements were taken during
      euglycaemic hyperinsulinaemia and saline infusion (SAL). Graphical and
      compartmental analyses were used to model liver data. RESULTS: Circulating NEFA
      increased approximately three-fold during IL/Hep, and declined by 81+/-7% in the
      SAL study ( p</=0.01). Both M (-28+/-7%) and HGU (-25+/-9%) were significantly
      lowered by NEFA elevation ( p=0.004 and p=0.035 respectively). In the whole data
      set, the decreases in M and HGU were positively correlated ( r=0.78, p=0.038). No
      evidence of [(18)F]FDG outflow was detected during the scanning time. HGU was
      correlated with the phosphorylation rate parameter ( r=0.71, p=0.003) as derived
      by compartmental modelling. CONCLUSIONS/INTERPRETATION: In healthy men, NEFA
      impair insulin-mediated HGU and whole-body glucose uptake to a similar extent.
      Our data suggest that multiple intracellular NEFA targets may concur to down
      regulate glucose uptake by the liver.

PMID- 15243706
TI  - Advanced backcross QTL analysis in progenies derived from a cross between a
      German elite winter wheat variety and a synthetic wheat (Triticum aestivum L.).
AB  - We report here the second advanced backcross quantitative trait locus (AB-QTL)
      analysis carried out in winter wheat. Seven agronomic traits were studied in a
      BC2F1 population derived from a cross between the German winter wheat variety
      Flair and the synthetic wheat line XX86 developed in Japan. We selected 111 BC2F1
      lines and genotyped these with 197 microsatellite markers. Field data for seven
      agronomic traits were collected from corresponding BC2F3 families that were grown
      at up to six locations in Germany. QTL analyses for yield and yield components
      were performed using single-marker regression and interval mapping. A total of 57
      putative QTLs derived from XX86 were detected, of which 24 (42.1%) were found to
      have a positive effect from the synthetic wheat XX86. These favourable QQTLs were
      mainly associated with thousand-grain weight and grain weight per ear. Many QTLs
      for correlated traits were mapped in similar chromosomal regions. The AB-QTL data
      obtained in the present study are discussed and compared with results from
      previous QTL analyses.

PMID- 15243705
TI  - Simple non-invasive assessment of advanced glycation endproduct accumulation.
AB  - AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the
      pathogenesis of chronic complications of diabetes mellitus and renal failure. All
      current measurements of AGE accumulation require invasive sampling. We exploited
      the fact that several AGE exhibit autofluorescence to develop a non-invasive tool
      for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We
      validated its use by comparing the values obtained using the AFR with the AGE
      content measured in extracts from skin biopsies of diabetic and control subjects.
      METHODS: Using the AFR with an excitation light source of 300-420 nm,
      fluorescence of the skin was measured at the arm and lower leg in 46 patients
      with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the
      majority of whom were Caucasian. Autofluorescence was defined as the average
      fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of
      the average fluorescence per nm over the 300-420-nm range. Skin biopsies were
      obtained from the same site of the arm, and analysed for collagen-linked
      fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)
      (carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). RESULTS:
      Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62,
      p</=0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were
      above the 95% CI of the mean value in control subjects, and correlated with age,
      diabetes duration, mean HbA(1)c of the previous year and creatinine levels.
      CONCLUSIONS/INTERPRETATION: The AFR offers a simple alternative to invasive
      measurement of AGE accumulation and, to date, has been validated in non-pigmented
      skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of
      AGE-related long-term complications in diabetes mellitus and in other conditions
      associated with AGE accumulation.

PMID- 15243707
TI  - A QTL that enhances and broadens Bt insect resistance in soybean.
AB  - Effective strategies are needed to manage insect resistance to Bacillus
      thuringiensis (Bt) proteins expressed in transgenic crops. To evaluate a multiple
      resistance gene pyramiding strategy, eight soybean (Glycine max) lines possessing
      factorial combinations of two quantitative trait loci (QTLs) from plant
      introduction (PI) 229358 and a synthetic Bt cry1Ac gene were developed using
      marker-assisted selection with simple sequence repeat markers. Field studies were
      conducted in 2000 and 2001 to evaluate resistance to corn earworm (Helicoverpa
      zea) and soybean looper (Pseudoplusia includens), and detached leaf bioassays
      were used to test antibiosis resistance to Bt-resistant and Bt-susceptible
      strains of tobacco budworm (TBW; Heliothis virescens). Based on defoliation in
      the field and larval weight gain on detached leaves, lines carrying a combination
      of cry1Ac and the PI 229358 allele at a QTL on linkage group M were significantly
      more resistant to the lepidopteran pests, including the Bt-resistant TBW strain,
      than were the other lines. This is the first report of a complementary additive
      effect between a Bt transgene and a plant insect resistance QTL with an
      uncharacterized mode of action that was introgressed using marker-assisted
      selection.

PMID- 15243708
TI  - [Circadian rhythms in endocrinology].
AB  - The function and fission properties of every cell in the organism follow a
      distinct rhythm. The synchronization of all these peripheral rhythms is
      controlled by a superordinate "master-clock", which is located in the nucleus
      suprachiasmaticus of the hypothalamus. Endocrine systems, aside from the
      autonomic nervous system, serve as efferent signals to transmit the rhythm to
      peripheral organs. The measurement of time-dependent changes in circulating
      hormone concentrations allows conclusions concerning the functionality of
      circadian rhythms and therefore represents a central approach in endocrine
      research. Regarding the interpretation of diurnal changes, one has to keep in
      mind that apart from the light/dark cycle other factors like the sleep/wake cycle
      or food intake also clearly influence the secretory activity of many endocrine
      organs. The dissociation of intrinsic circadian rhythms from other influencing
      factors requires the performance of costly and well-controlled experimental
      studies. Moreover, because of the complex interactions between hormones it is
      necessary to assess diurnal changes in activity of various endocrine systems in
      parallel. Only such an approach enables to understand the impact of endocrine
      rhythms on the complexly regulated homeostasis of e.g. glucose metabolism or the
      immune system.

PMID- 15243709
TI  - [Hereditary periodic fever].
AB  - Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D periodic fever
      syndrome (HIDS), and tumor necrosis factor receptor-associated periodic syndrome
      (TRAPS) are hereditary periodic fever syndromes. FMF is caused by mutations in
      the Mediterranean fever gene, HIDS by mutations in the mevalonat-kinase gene, and
      TRAPS by mutations in the TNF-receptor superfamily 1A gene. Impaired function of
      the encoded proteins, i.e. pyrin in FMF, mevalonat-kinase in HIDS, and the p55
      TNF-receptor in TRAPS, induces a dysregulated cytokine balance. Clinical
      manifestations are relapsing fever, serositis, arthralgia, myalgia, and
      miscellaneous forms of rash. The diagnosis is made through moleculargenetic
      analysis of mutations of the MEFV-gene (FMF), MVK-gene (HIDS), or TNFRSF1A-gene
      (TRAPS). Colchicine is the therapy of choice in FMF. HIDS is treated
      symptomatically. Impaired TNF-alpha regulation in TRAPS can be treated with
      etanercept.

PMID- 15243711
TI  - [gamma-Hydroxybutyrate intoxication].
AB  - The drug gamma-Hydroxybutyrate (GHB), also known as liquid ecstasy, has now
      reached Europe. Estimating the dosage of liquid GHB is especially difficult
      leading to unintentional intoxication because the exact concentration is not
      known. We repeatedly had to treat young patients intoxicated by GHB in our
      intensive care unit. We describe the course and treatment of three patients with
      GHB intoxication. If alcohol or mixed intoxication with drugs detected in
      traditional hospital toxicological assays has been excluded as the cause of
      unconsciousness in young patients from disco's, an intoxication with GHB should
      be considered. The therapy is mainly symptomatic and supportive but monitoring in
      an intensive care unit with the option of short term respirator therapy is
      necessary. Serum and urine samples taken on arrival should be conserved for
      further investigation in a forensic institute.

PMID- 15243710
TI  - [Survey on current practice of regional anaesthesia in Germany, Austria, and
      Switzerland. Part 2: Use, success rates and techniques].
AB  - The current practice of regional anaesthesia in German-speaking countries was
      investigated in a survey. The second part of the trilogy presents data about its
      use, success rates, and techniques. In 2002 questionnaires were mailed to 750
      randomly selected departments of anaesthesia of which 384 hospitals participated.
      Peripheral regional anaesthesia is used above all in traumatology and
      orthopaedics, 45% of the hospitals with paediatric surgery never used neuroaxial
      blocks. The residents achieved mean success rates of 69.7+/-11.8% for
      supraclavicular plexus block to 85.5+/-9.0% for spinal anaesthesia, the
      specialists in anaesthesia 79.2+/-11.3% (supraclavicular plexus block) to 91.0+/
      6.8% (spinal anaesthesia). Standards for basic techniques, recording of success
      rates, and for quality assurance of peripheral nerve blocks should be worked out
      to improve the application of peripheral regional anaesthesia procedures. In
      neuroaxial anaesthesia satisfying success rates were reached in German-speaking
      countries. In paediatric anaesthesia its use still has many opponents.

PMID- 15243712
TI  - Endoscopic aqueductoplasty in the treatment of aqueductal stenosis.
AB  - OBJECTIVE: Endoscopic aqueductoplasty is an option in the treatment of
      obstructive hydrocephalus caused by aqueductal stenoses. We report on our
      experience with this endoscopic technique, focussing on indications, operative
      technique, and results. METHODS: A series of 39 endoscopic aqueductoplasties was
      performed in 33 patients harbouring a hydrocephalus caused by aqueductal
      stenosis. In 13 patients, a third ventriculostomy was simultaneously performed.
      There was no endoscopy-related mortality. One aqueductoplasty had to be
      abandoned. In 7 patients, reclosure of the restored aqueduct required an
      endoscopic revision. In 25 patients (76%), the hydrocephalus-related symptoms
      resolved or improved. The condition was unchanged in 8 patients. Four patients
      needed to be shunted. The ventricles decreased in size in 22 patients (67%), were
      larger in 2, and unchanged in the remaining 9 patients. CONCLUSION: Endoscopic
      aqueductoplasty is a treatment option in patients with hydrocephalus caused by
      membranous aqueductal stenosis. Unfortunately, the reclosure rate is higher than
      initially expected. More experience and longer follow-up are necessary to
      determine the value of endoscopic aqueductoplasty in the treatment of
      hydrocephalus caused by aqueductal stenosis.

PMID- 15243713
TI  - The role of neuroendoscopy in the management of tectal gliomas.
AB  - OBJECTIVES: The objective was to determine the role of neuroendoscopy in the
      management of tectal plate gliomas. METHODS: Clinical and radiological data of
      children and adults who underwent neuroendoscopy were reviewed. Successful
      outcome was defined as shunt-freedom and resolution of symptoms and signs of
      raised intracranial pressure. RESULTS: Between 1 April 1998 and 31 March 2003, 11
      patients (6 males and 5 females) underwent endoscopic third ventriculostomy (ETV)
      for the management of hydrocephalus secondary to a tectal plate glioma. This
      comprises 4% of 258 patients who have undergone neuroendoscopic procedures in our
      unit. The median age at the time of surgery was 19 (range 9-59) years. In 4
      patients endoscopic biopsy of the tumour was performed at the same time. During a
      median follow-up period of 31 months (range 2-45), 4 patients underwent a second
      ETV, of whom 2 subsequently required insertion of ventriculoperitoneal (VP)
      shunts. Nine patients (82%) remain shunt-independent. Of the 4 tumours that were
      biopsied, a histological diagnosis of low-grade astrocytoma was made with
      certainty in only 2 cases. All tumours remained unchanged on follow-up MR
      imaging. CONCLUSIONS: Endoscopic third ventriculostomy can result in excellent
      control of hydrocephalus in patients with tectal plate gliomas. Tectal gliomas
      appear to be very slow growing tumours that can be managed conservatively in
      adults as well as children. Longer follow-up in larger studies is required.

PMID- 15243714
TI  - Mechanisms of heavy-metal sequestration and detoxification in crustaceans: a
      review.
AB  - This review is an update of information recently obtained about the
      physiological, cellular, and molecular mechanisms used by crustacean organ
      systems to regulate and detoxify environmental heavy metals. It uses the American
      lobster, Homarus americanus, and other decapod crustaceans as model organisms
      whose cellular detoxification processes may be widespread among both
      invertebrates and vertebrates alike. The focus of this review is the decapod
      hepatopancreas and its complement of metallothioneins, membrane metal transport
      proteins, and vacuolar sequestration mechanisms, although comparative remarks
      about potential detoxifying roles of gills, integument, and kidneys are included.
      Information is presented about the individual roles of hepatopancreatic
      mitochondria, lysosomes, and endoplasmic reticula in metal sequestration and
      detoxification. Current working models for the involvement of mitochondrial and
      endoplasmic reticulum calcium-transport proteins in metal removal from the
      cytoplasm and the inhibitory interactions between the metals and calcium are
      included. In addition, copper transport proteins and V-ATPases associated with
      lysosomal membranes are suggested as possible sequestration processes in these
      organelles. Together with several possible cytoplasmic divalent and trivalent
      anions such as sulfate, oxalate, or phosphate, accumulations of metals in
      lysosomes and their complexation into detoxifying precipitation granules may be
      regulated by variations in lysosomal pH brought about by bafilomycin-sensitive
      proton ATPases. Efflux processes for metal transport from hepatopancreatic
      epithelial cells to the hemolymph are described, as are the possible roles of
      hemocytes as metal sinks. While some of the cellular processes for isolating
      heavy metals from general circulation occur in the hepatopancreas and are
      beginning to be understood, very little is currently known about the roles of the
      gills, integument, and kidneys in metal regulation. Therefore, much remains to be
      clarified about the organs and mechanisms involved in metal homeostasis in
      decapod crustaceans.

PMID- 15243715
TI  - The positive predictive value of the breast imaging reporting and data system (BI
      RADS) as a method of quality assessment in breast imaging in a hospital
      population.
AB  - Evaluation of the diagnostic performance of mammography and US in our hospital,
      based upon the positive predictive value (PPV) for breast cancer of the breast
      imaging reporting and data system (BI-RADS) final assessment categories, has been
      performed. A follow-up study of 2,762 mammograms was performed, along with 955
      diagnostic exams and 1,807 screening exams. Additional US was performed in 655
      patients (23.7%). The combined reports were assigned a BI-RADS category. Follow
      up was obtained by pathologic examination, mammography at 12 months or from
      PALGA, a nationwide network and registry of histo- and cytopathology. Overall
      sensitivity was 85% (specificity 98.7%); sensitivity of the diagnostic
      examinations was 92.9% (specificity 97.7%) and of the screening examinations
      69.2% (specificity 99.2%). The PPV of BI-RADS 1 was 5 of 1,542 (0.3%), and of BI
      RADS 2, it was 6 of 935 (0.6%). BI-RADS 3 was 6 of 154 (3.9%), BI-RADS 4 was 39
      of 74 (52.7%) and BI-RADS 5 was 57 of 57 (100%). The difference between BI-RADS 1
      and 2 vs. BI-RADS 3 was statistically significant (P<0.01). Analysis of BI-RADS 3
      cases revealed inconsistencies in its assignment. Evaluation of the BI-RADS final
      assessment categories enables a valid analysis of the diagnostic performance of
      mammography and US and reveals tools to improve future outcomes.

PMID- 15243716
TI  - Comparison of whole-body STIR-MRI and 99mTc-methylene-diphosphonate scintigraphy
      in children with suspected multifocal bone lesions.
AB  - The study was performed to compare whole-body short time inversion recovery
      (STIR) MR imaging and (99m)Tc-methylene diphosphonate planar scintigraphy in the
      examination of children with suspected multifocal skeletal malignant lesions.
      Sixteen patients with known or suspected malignant skeletal disease underwent
      both whole-body STIR MR imaging and bone scintigraphy. The lesions were described
      and numbered according to scintigraphic evaluation criteria. Thus, 16 regions
      were analyzed in each patient for the comparison between the two modalities.
      Histology was proven in the primary malignant regions. Follow-up MRIs were
      registered. Scintigraphy and MRI follow-up were evaluated as gold standard. A
      total of 139 different lesions was observed by both modalities. Baseline whole
      body MRI revealed 119 bone lesions in 256 possible sites (46.5%); scintigraphy
      revealed only 58 lesions (22.6%). Congruence was observed in only four patients
      (25%). According to the location of the lesion, correlation was observed in
      39/139 lesions (28%). In all, 57.5% of the lesions were detected only by MRI and
      14.5% of the lesions were detected only by scintigraphy. Whole-body MRI was more
      sensitive (P<0.001). Of all lesions numbered which could be separated in the
      initial MRI, whole-body MRI detected 178 lesions in the patients. The results
      suggest that whole-body MRI using a STIR sequence is an effective radiation free
      method for examination of children with suspected multifocal bone lesions. MRI
      showed more lesions than conventional (99m)Tc-methylene diphosphonate
      scintigraphy. Therefore, whole-body MRI may be feasible as a screening modality
      for metastatic and skip lesions in osteosarcoma, PNET, Ewing sarcoma and
      Langerhans cell histiocytosis in children.

PMID- 15243717
TI  - Virtual endoscopy of the nasopharynx in the evaluation of its normal anatomy and
      alterations due to lymphoid hyperplasia: preliminary report.
AB  - The purpose of this study was to evaluate the diagnostic usefulness of virtual
      endoscopy in establishing the anatomic appearance of nasopharynx, both normal and
      affected by lymphoid hyperplasia. Thirty-seven patients affected by chronic
      rhinosinusal and otomastoid pathology, all studied by rhinoscopy, were examined
      with multislice computed tomography (CT) and virtual endoscopy of the
      nasopharynx. Rhinoscopy showed a completely normal nasopharynx in 15 cases and a
      variable grade of lymphoid hypertrophy in 22 patients. A general agreement was
      observed between traditional and virtual endoscopy findings in both subgroups.
      The tasca of Luschka was detected in 13/15 of normal subjects and only in 3/22
      patients. The Rosenmuller fossae appeared deeper in normal subjects and their
      symmetry could be considered an important criterion of normality. In all cases, a
      good evaluation of the tubaric ostium was obtained. Differentiation between
      hyperplasic lymphoid tissue and neoplasms is possible only in lymphoid
      hyperplasia characterized by median crest-like swelling with a narrow base. In
      most cases, differential diagnosis cannot be based only on morphological criteria
      of virtual endoscopy, but it should be evaluated considering the overall CT
      findings and clinical presentation.

PMID- 15243718
TI  - Kikuchi's disease involving the supraclavicular lymph nodes and associated with
      transient eruption.
AB  - A 26-year-old woman presented with high fever, marked supraclavicular
      lymphadenopathy, and morbilliform eruptions and was diagnosed with Kikuchi's
      disease (KD) based on pathologic findings from biopsied lymph nodes. All her
      manifestations of KD improved, however, without any specific treatment. The
      picture of transient morbilliform eruptions typified in KD here is seldom shown
      in the literature. In general, KD would run a benign course of supraclavicular
      lymphadenopathy.

PMID- 15243719
TI  - Sestamibi scintigraphy reveals adenocarcinoma of the lung.

PMID- 15243720
TI  - Genes of the constant regions of functional immunoglobulin heavy chain of
      Japanese flounder, Paralichthys olivaceus.
AB  - IgM and IgD genes of the Japanese flounder were cloned and characterized from a
      genomic bacterial artificial chromosome (BAC) library. The micro gene contained
      four constant region exons (Cmi1-Cmi4), and two transmembrane exons (miTM1 and
      miTM2), which conforms to the organizational pattern of all other vertebrate
      micro-chain genes examined so far. In the same BAC clone, the delta gene, which
      is homologous to the IgD gene in mammals and teleost fish, was found immediately
      (0.9 kb) downstream of the IgM gene. This gene encoded seven exons (Cdelta1
      Cdelta7) and two deltaTM exons (deltaTM1 and deltaTM2) and had no duplication of
      Cdelta1-Cdelta2, as found in Atlantic cod, or Cdelta2-Cdelta3-Cdelta4, as found
      in Atlantic salmon and channel catfish. Phylogenetic and sequence analyses
      strongly suggest that teleost delta is more closely related to non-IgM isotypes
      than IgM isotypes. The heavy chain (IgH) locus of Japanese flounder, which
      encodes microm, micros and deltam, was found to be fully functional.

PMID- 15243721
TI  - Effects of intracellular magnesium on Kv1.5 and Kv2.1 potassium channels.
AB  - We characterized the effects of intracellular Mg(2+) (Mg(2+) (i)) on potassium
      currents mediated by the Kv1.5 and Kv2.1 channels expressed in Xenopus oocytes.
      Increase in Mg(2+) (i) caused a voltage-dependent block of the current amplitude,
      apparent acceleration of the current kinetics (explained by a corresponding shift
      in the steady-state activation) and leftward shifts in activation and
      inactivation dependencies for both channels. The voltage-dependent block was more
      potent for Kv2.1 [dissociation constant at 0 mV, K(d)(0), was approximately 70 mM
      and the electric distance of the Mg(2+) binding site, delta, was 0.2] than for
      the Kv1.5 channel [K(d)(0) approximately 40 mM and delta = 0.1]. Similar shifts
      in the voltage-dependent parameters for both channels were described by the Gouy
      Chapman formalism with the negative charge density of 1 e(-)/100 A(2).
      Additionally, Mg(2+) (i) selectively reduced a non-inactivating current and
      increased the accumulation of inactivation of the Kv1.5, but not the Kv2.1
      channel. A potential functional role of the differential effects of Mg(2+) (i) on
      the Kv channels is discussed.

PMID- 15243722
TI  - Effect of the frequency of transcutaneous electrical nerve stimulation on
      analgesia during extracorporeal shock wave lithotripsy.
AB  - In this prospective, randomised, sham controlled study, we set out to determine
      which transcutaneous electrical nerve stimulation (TENS) therapy modality
      (conventional vs acupuncture-like) is more effective as a supplementary analgesic
      regimen during extracorporeal shock wave lithotripsy (ESWL). Patients were
      prospectively randomised to one of three groups. In Group I (n=22), conventional
      TENS (impulse pattern: continuous at 80 Hz; intensity: 10-30 mA) was applied. In
      Group II (n=22) acupuncture-like TENS (impulse pattern: burst at 2 Hz; intensity:
      15-50 mA) was applied. In Group III (n=22) (control group), stimulation was
      started at 1 mA and the intensity increased to no more than 10 mA until it
      produced a tickling sensation. Alfentanil was administered through a patient
      controlled analgesic device. Alfentanil consumption, hemodynamics and respiratory
      parameters, a 10-cm visual analogue pain scale, patient satisfaction, recovery
      and discharge times were evaluated. The consumption of alfentanil was
      significantly lower in Group I than in Groups II and III (P<0.0001). Pain scores
      were lower in Group I than in the other two groups (P<0.05). Patients in Group I
      were more satisfied with their analgesic medication than those in the other two
      groups (P<0.05). Both the time to an Aldrete score >8 and a modified post
      anaesthetic discharge score >8 were significantly shorter in Group I (2.3+/-1.8,
      49.1+/-14.6) than those of Groups II (4.6+/-2.2, 60.2+/-18.1) and III (4.9+/-2.8,
      58.4+/-16.5) (P<0.0001 and P<0.05, respectively). We conclude that the use of
      conventional TENS is effective in decreasing the analgesic requirements and the
      incidence of alfentanil-related side effects during ESWL.

PMID- 15243723
TI  - Bilateral orbital tumour as the presentation of mammographically occult breast
      cancer.
AB  - We report a rare case of bilateral orbital metastases as the presentation in a 63
      year-old woman. Biopsy of a diffusely infiltrated medial rectus muscle suggested
      metastatic adenocarcinoma. Investigation revealed a palpable mass of the right
      breast not shown on mammography or sonography. Invasive lobular carcinoma was
      found at core-needle biopsy with histological features identical to those of the
      orbital lesion. Metastases to the extraocular muscles are uncommon, particularly
      as the initial abnormality in the absence of disseminated disease.

PMID- 15243724
TI  - Transluminal color-coded three-dimensional magnetic resonance angiography for
      visualization of signal intensity distribution pattern within an unruptured
      cerebral aneurysm: preliminarily assessment with anterior communicating artery
      aneurysms.
AB  - The natural history of unruptured cerebral aneurysm is not known; also unknown is
      the potential growth and rupture in any individual aneurysm. The authors have
      developed transluminal color-coded three-dimensional magnetic resonance
      angiography (MRA) obtained by a time-of-flight sequence to investigate the
      interaction between the intra-aneurysmal signal intensity distribution patterns
      and configuration of unruptured cerebral aneurysms. Transluminal color-coded
      images were reconstructed from volume data of source magnetic resonance
      angiography by using a parallel volume-rendering algorithm with transluminal
      imaging technique. By selecting a numerical threshold range from a signal
      intensity opacity chart of the three-dimensional volume-rendering dataset several
      areas of signal intensity were depicted, assigned different colors, and
      visualized transparently through the walls of parent arteries and an aneurysm.
      Patterns of signal intensity distribution were analyzed with three operated cases
      of an unruptured anterior communicating artery aneurysm and compared with the
      actual configurations observed at microneurosurgery. A little difference in
      marginal features of an aneurysm was observed; however, transluminal color-coded
      images visualized the complex signal intensity distribution within an aneurysm in
      conjunction with aneurysmal geometry. Transluminal color-coded three-dimensional
      magnetic resonance angiography can thus provide numerical analysis of the
      interaction between spatial signal intensity distribution patterns and aneurysmal
      configurations and may offer an alternative and practical method to investigate
      the patient-specific natural history of individual unruptured cerebral aneurysms.

PMID- 15243725
TI  - A quantitative measure of myelination development in infants, using MR images.
AB  - The objective of this study was to measure myelination of frontal lobe changes in
      infants and young children. Twenty-four cases of infants and children (age range
      12-121 months) were evaluated by a quantitative assessment of T2-weighted MR
      image features. Reliable quantitative changes between white and gray matter
      correlated with developmental age in a group of children with no neurological
      findings. Myelination appears to be an increasing exponential function with the
      greatest rate of change occurring over the first 3 years of life. The
      quantitative changes observed were in accordance with previous qualitative
      judgments of myelination development. Children with periventricular leukomalacia
      (PVL) showed delays in achieving levels of myelination when compared to normal
      children and adjusted for chronological age. The quantitative measure of
      myelination development may prove to be useful in assessing the stages of
      development and helpful in the quantitative descriptions of white matter
      disorders such as PVL.

PMID- 15243727
TI  - Sensory biases produce alternation advantage found in sequential saccadic eye
      movement tasks.
AB  - In two-choice reaction time tasks, participants respond faster when the correct
      decision switches across consecutive trials. This alternation advantage has been
      interpreted as the guessing strategies of participants. Because the participants
      expect that the correct decision will switch across consecutive trials, they
      respond faster when this expectation is confirmed and they respond more slowly
      when it is disconfirmed. In this study, we evaluated the veracity of this
      expectancy interpretation. After replicating a long-lasting alternation advantage
      in saccadic reaction times (Experiment 1), we show that reducing the
      participants' ability to guess with a challenging mental rotation task does not
      change the alternation advantage, which suggests that expectancy is not
      responsible for the effect (Experiment 2). Next, we used prosaccade and
      antisaccade responses to dissociate between the sensory and motor contributions
      of the alternation advantage (Experiment 3) and we found that the alternation
      advantage originates from sensory processing. The implications of these findings
      are discussed with regard to guessing strategies, sensory processing, and how
      these findings may relate to inhibition of return.

PMID- 15243726
TI  - Distinction between high-grade gliomas and solitary metastases using peritumoral
      3-T magnetic resonance spectroscopy, diffusion, and perfusion imagings.
AB  - This study compared the effectiveness of relative cerebral blood volume, apparent
      diffusion coefficient, and spectroscopic imaging in differentiating between
      primary high-grade gliomas and solitary metastases. A 3.0-T MR unit was used to
      perform proton MR spectroscopy, diffusion imaging, and conventional MR imaging on
      26 patients who had solitary brain tumors (14 high-grade gliomas and 12
      metastases). All diagnoses were confirmed by biopsy. Twelve perfusion MR studies
      (8 high-grade gliomas and 4 metastases) were also performed. The results showed
      that the choline to creatine ratio and relative cerebral blood volume in the
      peritumoral regions of high-grade gliomas were significantly higher than they
      were in the metastases. The apparent diffusion coefficient values in tumoral and
      peritumoral regions of metastases were significantly higher than they were in the
      primary gliomas. Although conventional MR imaging characteristics of solitary
      metastases and primary high-grade gliomas may sometimes be similar, the
      peritumoral perfusion-weighted and spectroscopic MR imaging enable distinction
      between the two. Diffusion-weighted imaging techniques were complementary
      techniques to make a differential diagnosis between the two malignant tumors.

PMID- 15243728
TI  - Accuracy of internal dynamics models in limb movements depends on stability.
AB  - This study investigated the ability to use an internal model of the environmental
      dynamics when the dynamics were predictable but unstable. Subjects performed goal
      directed movements using a robot manipulandum while counteracting a force field,
      which created instability by assisting the movement in proportion to hand
      velocity. Subjects' performance was better on the last trial than on the first
      trial in the force field for all four movement directions tested: out, in, right
      and left. Subjects adapted to the force field primarily by increasing muscle co
      contraction, compared to null field movements, during all phases of movement.
      This co-contraction generally declined for both the deceleration and
      stabilization phases during the course of the first 25 movements in each
      direction, but tended not to decrease significantly thereafter. Catch trials at
      the end of the learning period suggested that increased viscoelastic impedance
      due to muscle co-contraction was used to counteract the force field. Only in the
      case of outward movements were aftereffects observed that were consistent with
      formation of an accurate internal model of the force field dynamics.
      Stabilization of the hand for outward movements required less muscle co
      contraction than for movements in other directions due to stability conferred by
      the geometry of the arm. The results suggest that the accuracy of an internal
      model depends critically on the stability of the coupled dynamics of the limb and
      the environment.

PMID- 15243730
TI  - Independent effects of endogenous and exogenous spatial cueing: inhibition of
      return at endogenously attended target locations.
AB  - Inhibition of return (IOR) is thought to reflect a bias against returning
      attention to previously attended locations. According to this view, IOR should
      occur only if attention is withdrawn from the target location prior to target
      appearance. In the present study, endogenous attention and exogenous cueing were
      manipulated orthogonally. IOR was observed both when a target appeared at an
      unexpected location, and when a target appeared at the expected location. A
      similar pattern of results was obtained in a reanalysis of data from a study with
      Neglect patients. These results suggest that IOR is independent of endogenous
      orienting.

PMID- 15243729
TI  - Visual illusion in virtual world alters women's target-directed walking.
AB  - In this study we investigated whether a visual illusion located in far space
      alters a person's open-loop, target-directed walking path in the same manner as
      it alters the perception of the target's position. Through the use of immersive
      VR the subject was able to walk physically to the location of a target embedded
      in a scene that was manipulated to create a visual illusion, known as the induced
      Roelofs effect. This illusion has been shown to alter the perception of a
      target's position. The experiment consisted of two tasks: a perception task and
      an action task. In the perception task, subjects viewed the scene for 1 s, it
      disappeared, and they were to report the target's location verbally. The results
      showed that the visual illusion altered the reported positions in all but one
      subject. In the action task, subjects viewed the scene for 1 s, it disappeared,
      and the subjects were asked to walk to the target's location. The results showed
      that the illusion significantly altered the walking paths of most of the women
      and less than half of the men. A significant gender effect was observed; women's
      walking paths deviated, on average, by 7.1 degrees and men's, by only 2.0 degrees
      . These results indicate that action tasks in far space are susceptible to the
      effects of visual illusions, unlike the action tasks in near space that
      reportedly have been resistant to them. Furthermore, the significant gender
      effect suggests that men and women either have different strategies and/or employ
      different mechanisms when executing a visually guided task in far space.

PMID- 15243731
TI  - Stepping over obstacles: anticipatory modifications in children with and without
      Down syndrome.
AB  - The purpose of this study was to explore the mechanism of anticipatory control of
      gait in relation to the perception of an obstacle. Typically developing (TD)
      children (4-7 years of age) and children with Down syndrome (5-6 years of age)
      walked and stepped over obstacles of two different heights-a "subtle" obstacle
      that was placed at a very low distance from the floor (1% of total body height)
      and an "obvious" obstacle that was placed at a much higher distance from the
      floor (15% of total body height). Spatial and temporal measures of the gait cycle
      were analyzed. TD children showed increased variability in pre-obstacle step
      lengths only in response to the higher obstacle. Children with DS showed a
      decrease in variability in response to the higher obstacle and marked qualitative
      changes in their gait cycle. Both groups of children were able to scale toe
      clearance with obstacle height. These results show that TD young children can
      make task-specific anticipatory adjustments by modulating step length and toe
      clearance. Children with DS show appropriate scaling of toe clearance and are
      beginning to show the emergence of anticipatory responses under specific
      environmental conditions.

PMID- 15243732
TI  - Short-term effects of functional electrical stimulation on motor-evoked
      potentials in ankle flexor and extensor muscles.
AB  - Stimulating sensory afferents can increase corticospinal excitability. Intensive
      use of a particular part of the body can also induce reorganization of neural
      circuits (use-dependent plasticity) in the central nervous system (CNS). What
      happens in the CNS when the nerve stimulation is applied in concert with the use
      of particular muscle groups? The purpose of this study was to investigate short
      term effects of electrical stimulation of the common peroneal (CP) nerve during
      walking on motor-evoked potentials (MEPs) in the ankle flexors and extensors in
      healthy subjects. Since the stimulation was applied during the swing phase of the
      step cycle when the ankle flexors are active, this is referred to as functional
      electrical stimulation (FES). The following questions were addressed: (1) can FES
      during walking increase corticospinal excitability more effectively than
      passively received repetitive nerve stimulation and (2) does walking itself
      improve the descending connection. FES was delivered using a foot drop stimulator
      that activates ankle dorsiflexors during the swing phase of the step cycle. MEPs
      in the tibialis anterior (TA) and soleus muscles were measured before, between,
      and after periods of walking with or without FES, using transcranial magnetic
      stimulation. After 30 min of walking with FES, the half-maximum peak-to-peak MEP
      (MEP(h)) in the TA increased in amplitude and this facilitatory effect lasted for
      at least 30 min. In contrast, walking had no effects on the TA MEP(h) without
      FES. The increase in the TA MEP(h) with FES (approximately 40%) was similar to
      that with repetitive CP nerve stimulation at rest. The soleus MEP(h) was also
      increased after walking with FES, but not without FES, which differs from the
      previous observation with CP nerve stimulation at rest. With FES, the TA silent
      period at MEP(h) was unchanged or slightly decreased, while it increased after
      walking without FES. Increased cortical excitability accompanied by unchanged
      cortical inhibition (no changes in the silent period with FES) suggests that FES
      did not simply increase general excitability of the cortex, but had specific
      effects on particular cortical neurons.

PMID- 15243733
TI  - Platinum concentration in silicone breast implant material and capsular tissue by
      ICP-MS.
AB  - Inductively coupled plasma-mass spectrometry (ICP-MS) was used to determine the
      concentration of platinum (Pt) in silicone breast implant gel (range, 0.26-48.90
      microg g(-1) Pt; n=15), elastomer (range, 3.05-28.78 microg g(-1) Pt; n=7),
      double lumen (range, 5.79-125.27 microg g(-1) Pt; n=7), foam (range, 5.79-8.36
      microg g(-1) Pt; n=2), and capsular tissue (range, 0.003-0.272 microg g(-1) Pt;
      n=15). The results show that very high levels of Pt are present in the encasing
      elastomer, double lumen, and foam envelope materials. Silicone breast implants
      can be a source of significant Pt exposure for individuals with these implants.

PMID- 15243734
TI  - Adsorptive stripping voltammetric determination of cobalt in the presence of
      dimethylglyoxime and cetyltrimethylammonium bromide.
AB  - A sensitive procedure for determination of micro-traces of Co(II) by adsorptive
      stripping voltammetry is proposed. The procedure exploits the enhancement of the
      cobalt peak obtained by use of the system Co(II)-dimethylglyoxime-piperazine-1,4
      bis(2-ethanesulfonic acid)-cetyltrimethylammonium bromide. Using the optimized
      conditions, a detection limit (based on the 3 sigma criterion) for Co(II) of 1.2
      x 10(-11) mol L(-1) (0.7 ng L(-1)) was achieved. The calibration plot for an
      accumulation time of 30 s was linear from 5 x 10(-11) to 4 x 10(-9) mol L(-1).
      The procedure was validated by analysis of certified reference materials and
      natural water samples.

PMID- 15243735
TI  - A double-blind randomized study comparing imipramine with fluvoxamine in
      depressed inpatients.
AB  - OBJECTIVE: To compare the efficacy of imipramine and fluvoxamine in inpatients
      from two centers suffering from a depressive disorder according to DSM IV
      criteria. METHODS: The study included 141 patients with a depressive disorder
      according to DSM IV criteria. After a drug-free and placebo run-in period of 1
      week, patients were randomized to imipramine or fluvoxamine; doses of both drugs
      were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks
      after attaining predefined adequate plasma level. RESULTS: The mean age of the
      study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141
      patients, 56 had episode duration longer than 1 year, 48 had mood congruent
      psychotic features, and 138 patients received medication. Seven patients did not
      complete the medication trial. The total number of patients using concurrent
      medication was 12/138 (8.6%). On the primary outcome criteria patients on
      imipramine improved significantly better on the change of illness severity score
      of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no
      significant difference in 50% or more reduction on the HRSD, the other primary
      outcome criterion. On the secondary outcome criteria the mean reduction of the
      HRSD scores was significantly larger in the imipramine group than in the
      fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136,
      P=0.033). There was no significant difference in the number of patients with an
      HRSD < or =7 at the final evaluation. CONCLUSIONS: In depressed inpatients
      imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated
      by all patients.

PMID- 15243736
TI  - Progressive ratio performance following challenge with antipsychotics,
      amphetamine, or NMDA antagonists in adult rats treated perinatally with
      phencyclidine.
AB  - RATIONALE: Previous research has shown that rats exposed perinatally to
      phencyclidine (PCP) exhibited neuroanatomical abnormalities and altered
      cognition. In addition to cognitive deficits, schizophrenic patients may also
      exhibit negative symptoms such as lack of motivation. OBJECTIVES: In this study,
      we used a progressive ratio (PR) schedule of food reinforcement to assess
      motivation following early exposure to PCP. METHODS: Male rat pups were injected
      SC with 10 mg/kg PCP on postnatal days (PN) 7, 9, and 11. On PN 120, they began
      training in a PR 5 schedule of food reinforcement. RESULTS: Significant PCP
      effects on acquisition and baseline performance were not noted. After acquisition
      of the task, challenges with PCP, dizocilpine, amphetamine, haloperidol, and
      clozapine resulted in dose-dependent decreases in response rates of similar
      magnitudes in both groups. In rats that continued to respond at higher doses,
      PCP, dizocilpine, and clozapine failed to alter breakpoints. In contrast, a 5.6
      mg/kg dose of amphetamine selectively increased breakpoints in PCP-treated rats,
      although very few rats responded at this dose. Haloperidol decreased breakpoints
      in most rats at non-sedating doses. CONCLUSIONS: These results suggest that a
      regimen of perinatal PCP administration sufficient to disrupt cognition did not
      alter motivation for food reinforcement, regardless of whether rats also received
      challenges with NMDA antagonists or antipsychotics. Interpretation of
      amphetamine's high dose effects on breakpoints was complicated by the failure of
      many rats to respond at this dose. Further research is needed to determine
      whether negative symptoms such as social withdrawal may be modeled within this
      neurodevelopmental approach to schizophrenia.

PMID- 15243738
TI  - Haemangiopericytoma of the thyroid gland in combination with Hashimoto's disease.
AB  - We present a hitherto unique case of haemangiopericytoma (HP) of the thyroid
      gland in a 15-year-old female patient suffering from Hashimoto's disease for
      several months. Since angiogenesis has been discussed to play a major role in
      both diseases, we examined the expression of vascular endothelial growth factor
      (VEGF), VEGF receptors (VEGFRs) and platelet-derived growth factor receptors
      (PDGFRs). Most interestingly, strong expression of PDGFR alpha and beta was found
      in spindle-shaped tumour cells and tumour vessels in HP, while VEGF and VEGFR
      type I and -II were negative in these regions. In contrast, VEGF was expressed in
      the lymphoid infiltrate of Hashimoto's disease. Since PDGFR-beta is commonly
      expressed in pericytes, we suggest that the strong expression discovered in this
      study further supports the view that HP is derived from pericytes. The
      combination of HP and Hashimoto's disease is most probably a coincidental event.
      However, this case confirms previous reports demonstrating that in patients with
      Hashimoto's disease different neoplasias can occur.

PMID- 15243739
TI  - Accumulation of genes for susceptibility to rust fungi for which barley is nearly
      a nonhost results in two barley lines with extreme multiple susceptibility.
AB  - Nonhost resistance is the most common type of resistance in plants. Understanding
      the factors that make plants susceptible or resistant may help to achieve durably
      effective resistance in crop plants. Screening of 109 barley (Hordeum vulgare L.)
      accessions in the seedling stage indicated that barley is a complete nonhost to
      most of the heterologous rust fungi studied, while it showed an intermediate
      status with respect to Puccinia triticina, P. hordei-murini, P. hordei-secalini,
      P. graminis f. sp. lolii and P. coronata ff. spp. avenae and holci. Accessions
      that were susceptible to a heterologous rust in the seedling stage were much more
      or completely resistant at adult plant stage. Differential interaction between
      barley accessions and heterologous rust fungi was found, suggesting the existence
      of rust-species-specific resistance. In particular, many landrace accessions from
      Ethiopia and Asia, and naked-seeded accessions, tended to be susceptible to
      several heterologous rusts, suggesting that some resistance genes in barley are
      effective against more than one heterologous rust fungal species. Some barley
      accessions had race-specific resistance against P. hordei-murini. We accumulated
      genes for susceptibility to P. triticina and P. hordei-murini in two genotypes
      called SusPtrit and SusPmur, respectively. In the seedling stage, these
      accessions were as susceptible as the host species to the target rusts. They also
      showed unusual susceptibility to other heterologous rusts. These two lines are a
      valuable asset to further experimental work on the genetics of resistance to
      heterologous rust fungi.

PMID- 15243740
TI  - Characterization of tomato endo-beta-1,4-glucanase Cel1 protein in fruit during
      ripening and after fungal infection.
AB  - The tomato (Lycopersicon esculentum Mill.) endo-beta-1,4-glucanase (EGase) Cel1
      protein was characterized in fruit using specific antibodies. Two polypeptides
      ranging between 51 and 52 kDa were detected in the pericarp, and polypeptides
      ranging between 49 and 51 kDa were detected in locules. The polypeptides
      recognized by Cel1 antiserum in fruit are within the size range predicted for
      Cel1 protein and could be derived from heterogeneous glycosylation. Cel1 protein
      accumulation was examined throughout fruit ripening. Cel1 protein appears in the
      pericarp at the stage in which many ripening-related changes start, and remains
      present throughout fruit ripening. In locules, Cel1 protein is already present at
      the onset of fruit ripening and remains constant during fruit ripening. This
      pattern of expression supports a possible role for this EGase in the softening of
      pericarp tissue and in the liquefaction of locules that takes place during
      ripening. The accumulation of Cel1 protein was also analyzed after fungal
      infection. Cel1 protein and mRNA levels are down-regulated in pericarp after
      Botrytis cinerea infection but are not affected in locular tissue. The same
      behavior was observed when fruits were infected with Penicillium expansum,
      another fungal pathogen. Cel1 protein and mRNA levels do not respond to wounding.
      These results support the idea that the tomato Cel1 EGase responds to pathogen
      infection and supports a relationship between EGases, plant defense responses and
      fruit ripening.

PMID- 15243737
TI  - Pharmacogenetics of antipsychotic-induced weight gain.
AB  - RATIONALE: Antipsychotic medications have been associated with considerable
      weight gain. The degree of inter-individual variability and known genetic
      contributions to obesity suggest a combination of genetic and environmental
      factors. In the absence of established mechanisms and valid predictors for this
      relevant adverse effect, pharmacogenetic studies may provide the basis for the
      development of individualized treatment and preventive interventions. OBJECTIVE:
      The aim of the present review is to analyze the theoretical and empirical
      knowledge base for the selection of the most promising target genes that may
      contribute to antipsychotic-induced weight gain. METHODS: Examination of the
      preclinical and clinical literature that can inform the rational choice of target
      genes that may play a role in the development of adverse changes in body
      composition associated with antipsychotic treatment. RESULTS: Theoretically,
      candidate gene selection can be guided by knowledge about molecular pathways
      associated with obesity, receptors modulated by antipsychotic drugs, and enzymes
      implicated in their metabolism and bioavailability. While most available data
      relate to the general mechanisms of obesity and few studies have directly
      examined the genetic contributions to antipsychotic-induced weight gain, several
      genes warrant further investigation. These include the 5-HT(2C), pro
      opiomelanocortin, leptin, ghrelin, tumor necrosis factor alpha, adiponectin,
      dopamine D(2) receptor, histamine-H(1) receptor, and alpha(1), beta(2) and
      beta(3) adrenergic receptor genes. CONCLUSIONS: Pharmacogenetic studies can
      provide powerful tools for the pre-treatment identification of individuals at
      high risk for antipsychotic-induced weight gain, to uncover biological mechanisms
      that may even generalize to non-drug-induced weight gain, and to isolate novel
      targets for treatments of weight gain and obesity. To enhance power, future
      studies should pay close attention to population selection and avoidance/control
      of confounds, particularly past treatment exposure.

PMID- 15243741
TI  - Regulatory volume increase after secretory volume decrease in colonic epithelial
      cells under muscarinic stimulation.
AB  - To address the question of whether colonic secretory cells change their volume in
      response to carbachol (CCh) stimulation and, if so, the mechanisms involved
      therein, we used two-photon laser scanning microscopy to measure the volume of
      individual epithelial cells in the fundus region of crypts isolated from the
      guinea-pig distal colon. We also measured the volume of human colonic epithelial
      T84 cells using an electronic sizing technique. Both types of colonocytes
      responded to stimulation by CCh with shrinkage and then underwent a regulatory
      volume increase (RVI), even during continued stimulation by CCh. The secretory
      volume decrease (SVD) induced by CCh was antagonized by atropine, BAPTA loading
      and niflumic acid, a blocker of Ca(2+)-activated Cl(-) channels. An increase in
      the intracellular free [Ca(2+)] was observed with fura-2 during these volume
      responses to CCh. Removal of all Na(+) or K(+) or of most of the Cl(-) from the
      extracellular solution abolished the RVI, but not the preceding SVD. The RVI, but
      not the preceding SVD, was abolished by bumetanide, a blocker of the Na(+)-K(+)
      2Cl(-) cotransporter. We conclude that guinea-pig crypt colonocytes and human T84
      cells exhibit a cytosolic Ca(2+)-dependent SVD and undergo a subsequent RVI that
      is dependent on the operation of Na(+)-K(+)-2Cl(-) cotransporters.

PMID- 15243742
TI  - Protein kinase A inhibits intermediate conductance Ca2+-activated K+ channels
      expressed in Xenopus oocytes.
AB  - Intermediate-conductance (IK) Ca(2+)-activated K(+) channels are expressed in
      many different cell types where they perform a variety of functions including
      cell volume regulation, transepithelial secretion, lymphocyte activation and cell
      cycle progression. IK channels are thought to be regulated by phosphorylation;
      however, whether kinases act directly on the channel is unclear. Using IK
      channels heterologously expressed in Xenopus oocytes, we demonstrate that IK
      channels are potently inhibited (60%) by the catalytic subunit of protein kinase
      A (PKA). Inhibition of IK channel current by PKA is abolished by mutation of four
      phosphorylation residues (S312, T327, S332, and T348) in the putative calmodulin
      binding region of the channel. Evidence for direct modulation of the IK channel
      by PKA was further demonstrated using GST fusion proteins. The major site of
      phosphorylation was found to be serine 332; however, other residues were also
      phosphorylated. We conclude that IK channels can be directly regulated by the
      cAMP second-messenger system. The mechanism appears to involve direct
      phosphorylation by PKA of a modulatory locus in the cytoplasmic region of the
      channel, the site at which calmodulin is thought to interact. Modulation of IK
      channels by protein kinases may be an important mechanism regulating cell
      function.

PMID- 15243743
TI  - Chronic pain after hernia repair: a randomized trial comparing Shouldice,
      Lichtenstein and TAPP.
AB  - INTRODUCTION: Chronic pain after hernia repair is common, and it is unclear to
      what extent the different operation techniques influence its incidence. The aim
      of the present study was to compare the three major standardized techniques of
      hernia repair with regard to postoperative pain. PATIENTS AND METHODS: Two
      hundred and eighty male patients with primary hernias were prospectively,
      randomly selected to undergo Shouldice, tension-free Lichtenstein or laparoscopic
      transabdominal pre-peritoneal (TAPP) hernioplasty repairs. Patients were examined
      after 52 months with emphasis on chronic pain and its limitations to their
      quality of life. RESULTS: Chronic pain was present in 36% of patients after
      Shouldice repair, in 31% after Lichtenstein repair and in 15% after TAPP repair.
      Pain correlated with physical strain in 25% of patients after Shouldice, in 20%
      after Lichtenstein and in 11% after TAPP repair. Limitations to daily life,
      leisure activities and sports occurred in 14% of patients after Shouldice, 13%
      after Lichtenstein and 2.4% after TAPP repair. CONCLUSION: Chronic pain after
      hernia surgery is significantly more common with the open approach to the groin
      by Shouldice and Lichtenstein methods. The presence of the prosthetic mesh was
      not associated with significant postoperative complaints. The TAPP repair
      represents the most effective approach of the three techniques in the hands of an
      experienced surgeon.

PMID- 15243744
TI  - Laparoscopic surgery in situs inversus: a literature review and a report of
      laparoscopic sigmoidectomy for diverticulitis in situs inversus.
AB  - BACKGROUND: Situs inversus (SI) is a rare autosomal recessive congenital defect
      in which the position of abdominal and/or thoracic organs is a "mirror image" of
      the normal one, in the sagittal plain. In 25% of these cases, SI is part of the
      Kartagener syndrome, together with bronchiectasis and chronic sinusitis. METHODS:
      We present a case of a patient with Kartagener syndrome and complete SI that was
      laparoscopically operated on for diverticulitis. We also review the published
      English information available on this rare condition. RESULTS: A review of the
      literature revealed another single case of laparoscopic sigmoidectomy and 27
      cases of other laparoscopic interventions in the presence of SI. Those
      laparoscopic procedures included basic procedures such as explorations and
      cholecystectomies, as well as advanced procedures such as gastrectomy and gastric
      bypass. CONCLUSION: The laparoscopic approach is feasible in cases of SI,
      although technically more complicated because of the different position of the
      organs and the different laparoscopic view of the anatomy.

PMID- 15243746
TI  - Circadian variation in base rate measures of cardiac autonomic activity.
AB  - To investigate the role of the circadian pacemaker in autonomic modulation of
      base rate cardiac activity, 29 healthy subjects participated in a constant
      routine protocol. They were randomly divided into two groups in order to
      manipulate prior wakefulness. Group 1 started at 0900 hours immediately after a
      monitored sleep period, while group 2 started 12 h later. Measures of interbeat
      intervals (IBIs), respiratory sinus arrhythmia (RSA, an estimate of
      parasympathetic activity), pre-ejection period (PEP, an estimate of sympathetic
      activity), and core body temperature (CBT) were recorded continuously. Multilevel
      regression analyses (across-subjects) revealed significant 24- and/or 12-h
      sinusoidal circadian variation for CBT, IBI, and RSA, but not for PEP. Subject
      specific 24+12 h sinusoidal fits demonstrated a convergence of phase distribution
      for IBI and RSA of group 1 similar to CBT, while PEP showed a relatively large
      (i.e. random) distribution of phase. In group 2, all cardiac measures showed
      large distributions of phase. Unexpected results in the cardiac measures were
      found in group 2, probably caused by group differences in prior activation. Also,
      effects of sleep deprivation were observed for IBI and RSA in group 2.
      Consequently, all cardiac measures revealed significant sinusoidal x group
      interactions, a result not shown in CBT. These findings were interpreted as an
      indication for circadian endogenous parasympathetic modulation of cardiac
      activity that is mainly confounded by prior wakefulness that extends 24 h, while
      the sympathetic modulation is relatively uncoupled from the endogenous circadian
      drive and mainly influenced by prior activation.

PMID- 15243747
TI  - Factors affecting swimming economy in children and adults.
AB  - The aim of this study was to examine the influence of several explanatory
      factors: anthropometry, buoyancy, passive underwater torque, drag and swimming
      technique on the energy cost of swimming front crawl in children and adults.
      Submaximal V(.)O(2) was measured in ten children (age 12) and 13 adults (age 21),
      as well as body length (BL), body mass, arm length, propelling size, active drag,
      hydrostatic lift, passive torque, intracyclic velocity fluctuation, hand slip,
      stroke length and body angle. The results show that body length ( r=0.74), body
      mass ( r=0.86) propelling size ( r=0.61), arm length ( r=0.66), distance between
      the center of mass and the center of volume (Delta d, r=0.74) and body angle
      during swimming ( r=-0.56) all showed significant linear relationships with the
      cost of swimming at 1.0 m x s(-1) (CS(1.0)). When normalizing the cost of
      swimming to body size (CS(1.0) x BL(-1)) there were no differences between the
      two groups. The conclusions of this study are that the combination of BL, body
      mass, active drag factor, passive torque, drag efficiency and hydrostatic lift
      were able to explain 97% of the variation in the cost of swimming for the whole
      group of swimmers. The size-independent factors of torque and floating abilities
      (density and Delta d in % of BL), together with swimming technique and active
      drag were found to explain 75% of the variations in CS(1.0) x BL(-1). The
      identical values for CS(1.0) x BL(-1) for children and adults are explained
      through the opposing effects of a better swimming technique in the adults, and a
      better passive torque in the children.

PMID- 15243748
TI  - The relationship between exercise-induced oxidative stress and the menstrual
      cycle.
AB  - The purpose of this study was to investigate the relationship between exercise
      induced oxidative stress and the menstrual cycle in healthy sedentary woman.
      Eighteen women with regular menstrual cycles participated in this research. The
      subjects monitored their basal body temperature (BBT) and carried out a urinary
      ovulation test (twice) for 2 months prior to the study to determine their
      menstrual cycle. The subjects performed bicycle ergometer exercise (for 30 min at
      60% V(.)>O(2max)) in each phase (menses, follicular and luteal phases) of the
      menstrual cycle. Serum estradiol and progesterone concentrations were determined
      from blood that was collected at rest. Serum thiobarbituric acid reactive
      substances (TBARS), total superoxide dismutase (T-SOD) and extracellular
      superoxide dismutase (EC-SOD) were determined as markers of oxidative stress in
      blood samples collected at rest and after exercise. TBARS was significantly lower
      after exercise [2.4 (0.5) nmol/ml] in the follicular phase, and T-SOD was
      significantly lower after exercise [3.2 (1.2) U/ml] in the luteal phase. EC-SOD
      did not show a significant change after exercise during each phase of the
      menstrual cycle. Furthermore, there was a negative correlation between estradiol
      and DeltaT-SOD ( r=-0.46, P<0.05) and between estradiol and DeltaEC-SOD ( r=
      0.55, P<0.05) during the menses. All data are presented as the mean value and its
      standard deviation. The results of this study suggest that when the estradiol
      level is high in a menstrual cycle, free radicals produced as a consequence of
      exercise may be easily eliminated by sedentary women with normal menstrual
      cycles.

PMID- 15243749
TI  - Upper trapezius muscle conduction velocity during fatigue in subjects with and
      without work-related muscular disorders: a non-invasive high spatial resolution
      approach.
AB  - The development of fatigue at the muscle fibre level can be assessed in terms of
      a decrease in conduction velocity (CV). The present study aimed to investigate if
      work-related muscular disorders in occupations characterised by static loads of
      long duration affect fatigue resistance in the painful muscle. A group of eight
      secretaries suffering from bilateral chronic muscle pain in the shoulder/neck
      region was compared to a group of healthy subjects. The upper trapezius muscle
      was studied under isometric contractions, holding the arm in the horizontal plane
      up to the endurance point. Changes in CV estimated at the motor unit level were
      investigated using a non-invasive high spatial resolution electromyographic (EMG)
      approach. In addition, the number of motor unit potentials per second (PPS), and
      the root mean square (RMS) of bipolar signals were assessed, and the results
      reported as the mean and standard error for each value. Subjects with work
      related disorders showed less pronounced changes in CV with respect to healthy
      subjects. No differences between subjects with and without work-related disorders
      were encountered for the PPS and RMS. The present findings on CV indicate an
      increased fatigue-related recruitment of MUs in the painful muscle with respect
      to a healthy muscle. The fact that this recruitment is not reflected in the PPS
      and RMS estimates might be due to a fatigue-induced decrease in the firing rate
      and/or the de-recruitment of fatigued MUs. Furthermore, methodological
      limitations of the adopted method in the estimation of 'global' parameters such
      as the PPS and RMS have to be considered.

PMID- 15243750
TI  - Effects of spontaneously chosen crank rate variations on electromyographic
      responses in sub-maximal arm exercise in inexperienced subjects.
AB  - The aim of the present study was to compare electromyographic responses during
      arm exercises with a crank rate chosen spontaneously ( T(S)) or set at 20% below
      or above ( T(-20), T(+20)) the spontaneously chosen crank rate (SCCR). Ten male
      physical education students performed arm exercises with intensities ranging from
      20% to 80% of maximal power. Muscular activity levels were analysed for the
      biceps brachii and the triceps brachii muscles using integrated rectified surface
      electromyography (iEMG). All values were presented as the mean and standard
      deviation. During T(S), the sum of iEMG for the two muscles studied was
      significantly ( P<0.05) lower than during T(+20) for each power output. No
      significant differences were observed in iEMG values between T(S) and T(-20). The
      hypothesis that SCCR relates to a minimisation of muscle activation during an
      upper body exercise was not confirmed. Variations superior or inferior to a 20%
      increase of the iEMG responses do not influence it. Moreover, the selection of
      crank rates depends on the power output and the SCCR increased significantly (
      P<0.05) with increasing power output.

PMID- 15243752
TI  - Reconstruction of a case of thallium poisoning using LA-ICP-SFMS.
AB  - The unique capabilities of laser ablation in combination with inductively coupled
      plasma sector field mass spectrometry (LA-ICP-SFMS) were employed to reconstruct
      details of a homicide by thallium poisoning, which took place 38 years ago in
      Austria. Thallium was determined in several human bone samples after acid
      digestion in a microwave oven. The ICP-SFMS results showed that the thallium
      concentration in the victim's bones was in the range 1.07-2.63 microg g(-1),
      which is up to 170 times higher compared to concentrations found in bones of
      persons who have died due to natural causes. The results were in accordance with
      the values obtained by graphite furnace atomic absorption spectrometry (GF-AAS).
      Laser ablation ICP-SFMS was applied to assess the time interval between the
      victim's poisoning and death. Several line scans with a laser spot size of 50 mum
      were performed on a thumbnail of the poisoned person and on a reference thumbnail
      by laser ablation ICP-SFMS. Thallium peaks were detected on the nail of the
      victim at a distance of 2.5 mm from the younger edge of the nail.

PMID- 15243751
TI  - Mitochondrial transmembrane potential is diminished in phorbol myristate acetate
      stimulated peritoneal resident macrophages isolated from wild-type mice, but not
      in those from gp91-phox-deficient mice.
AB  - Macrophages produce superoxide (O2-) during phagocytosis or upon stimulation with
      a variety of agents including phorbol myristate acetate (PMA) through the
      activation of NADPH oxidase, and the formed O2- is converted to other reactive
      oxygen species (ROS) such as hydrogen peroxide (H2O2). The aim of the present
      study was to elucidate the effect of the intracellularly produced ROS on
      mitochondrial transmembrane potential (MTP) in mouse (C57BL/6) peritoneal
      resident macrophages stimulated with PMA. Using a fluorescent dye, succinimidyl
      ester of dichlorodihydrofluorescein (H2DCFDA), O2- was visualized in
      intracellular compartments in a certain subpopulation of macrophages isolated
      from wild-type mice. Cells deficient in gp91-phox, one of the membrane components
      of NADPH oxidase, were negative for the fluorescence. When cells were loaded with
      both H2DCFDA and MitoCapture, a fluorescent dye for mitochondria, mitochondrial
      fluorescence was diminished in O2- -producing cells, but not in O2- -deficient
      cells. Flow cytometry also revealed the decrease of mitochondrial fluorescence in
      wild-type cells, but not in gp91-phox-deficient cells. The loss of mitochondrial
      fluorescence was prevented by microinjection of catalase into cells. The present
      findings demonstrate that MTP is diminished by ROS, including the H2O2 dismutated
      from O2-, produced intracellularly by activation of the NADPH oxidase in mouse
      peritoneal resident macrophages stimulated with PMA.

PMID- 15243754
TI  - Ovarian cyst in juvenile hypothyroidism.
AB  - CASE REPORT: A case of primary hypothyroidism in a pre-pubertal girl presenting
      with vaginal bleeding and unilateral ovarian cyst is reported. The cyst resolved
      spontaneously after the institution of thyroid hormone therapy. CONCLUSION:
      Watchful expectancy is recommended when an ovarian cyst is found in association
      with primary hypothyroidism and precocious puberty.

PMID- 15243753
TI  - Viability of X-autosome translocations in mammals: an epigenomic hypothesis from
      a rodent case-study.
AB  - X-autosome translocations are highly deleterious chromosomal rearrangements due
      to meiotic disruption, the effects of X-inactivation on the autosome, and the
      necessity of maintaining different replication timing patterns between the two
      segments. In spite of this, X-autosome translocations are not uncommon. We here
      focus on the genus Taterillus (Rodentia, Gerbillinae) which provides two sister
      lineages differing by two autosome-gonosome translocations. Despite the recent
      and dramatic chromosomal repatterning characterising these lineages, the X
      autosome translocated species all display intercalary heterochromatic blocks
      (IHBs) between the autosomal and the ancestral sexual segments. These blocks,
      composed of highly amplified telomeric repeats and rDNA clusters, are not
      observed on the chromosomes of the non-translocated species, nor the Y1 and Y2 of
      the translocated species. Such IHBs are found in all mammals documented for X
      autosome translocation. We propose an epigenomic hypothesis which explains the
      viability of X-autosome translocations in mammals. This posits that constitutive
      heterochromatin is probably selected for in X-autosome translocations since it
      may (1) prevent facultative heterochromatinization of the inactivated X from
      spreading to the autosomal part, and (2) allow for the independent regulation of
      replication timing of the sex and autosomal segments.

PMID- 15243755
TI  - Erythema multiforme major following docetaxel.
AB  - OBJECTIVE: The objective was to report a severe skin reaction, erythema
      multiforme major, following administration of docetaxel. CASE SUMMARY: A female
      patient receiving weekly docetaxel for metastatic breast cancer developed a
      severe skin reaction characterized by blistering target lesions on her upper and
      lower extremities as well as painful ulcers of her oropharynx. The diagnosis of
      erythema multiforme major was made and high-dose hydrocortisone began, with
      gradual resolution of her symptoms. DISCUSSION: The semi-synthetic taxoid
      docetaxel, which is increasingly being used in the treatment of breast cancer,
      has been associated with several adverse skin reactions, including
      hypersensitivity, nail pigmentation, nail onycholysis, erythrodysethesia, and
      scleroderma. We report the first case of erythema multiforme major (Stevens
      Johnson syndrome) following docetaxel. Erythema multiforme major is a rare
      inflammatory skin disease associated with certain drugs (i.e., sulfonamides, non
      steroidal anti-inflammatory agents, anticonvulsants). It is characterized by a
      distinguishing target skin lesion and ulceration of mucosal surfaces. In severe
      cases, systemic manifestations such as pneumonitis can also occur. Treatment
      involves use of moderate to high-dose corticosteroids. SUMMARY: Clinicians using
      docetaxel should be aware of the variety of skin reactions that can occur, how
      they can be avoided and their severity reduced. Severe skin reactions such as
      occurred with our patient should be recognized and treated promptly in
      consultation with a dermatologist.

PMID- 15243757
TI  - Hydramnios and small for gestational age are independent risk factors for
      neonatal mortality and maternal morbidity.
AB  - OBJECTIVE: The objective was to evaluate the contribution of hydramnios and small
      for gestational age (SGA) as a combined pathology to maternal and neonatal
      morbidity and mortality. METHODS: The study population consisted of 192 SGA
      neonates with hydramnios, 5,515 SGA neonates with a normal amount of amniotic
      fluids, 3,714 appropriate for gestational age (AGA) neonates with polyhydramnios
      and 83,763 AGA neonates with a normal amount of amniotic fluid. A cross-sectional
      population based study was designed between the four study groups. Multiple
      logistic regression analysis was used to assess the contribution of these
      abnormalities and different risk factors to maternal and perinatal complications.
      RESULTS: The combination of hydramnios/SGA was found to be an independent risk
      factor for perinatal mortality (OR 20.55; CI 12.6-33.4). Congenital anomalies,
      prolapse of cord, hydramnios, SGA and grand multiparity were also independent
      risk factors for perinatal mortality. Independent risk factors for neonatal
      complications were prolapse of umbilical cord (OR 4.13; 95% CI 1.48-11.5),
      hydramnios/SGA (OR 2.72; 95% CI 1.81-4.07), chronic hypertension (OR 2.45; 95% CI
      1.02-5.9), congenital malformations (OR 1.93; 95% CI 1.14-3.24) and SGA (OR 1.47;
      95% CI 1.07-2). Significant independent risk factors for medical interventions
      during labor were fetal distress (OR 198.46; 95% CI 47.27-825.27), GDM Class B-R
      (OR 21.22; 95% CI 2.34-192.25), GDM class A (OR 4.64; 95% CI 2.62-8.21), severe
      pregnancy-induced hypertension (PIH; OR 7.74; 95% CI 2.35-25.42), hydramnios (OR
      1.95; 95% CI 1.3-2.91), hydramnios/SGA (OR 1.84; 95% CI 1.12-3.02) and
      malpresentation (OR 1.56; 95% CI 1.32-1.84). CONCLUSION: The combination of
      hydramnios and SGA is an independent risk factor for perinatal mortality and
      maternal complications. We suggest that the growth restriction of these fetuses
      is responsible for the neonatal complications, while the hydramnios contributes
      mainly to maternal complications.

PMID- 15243756
TI  - High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid
      between patients with and without endometriosis.
AB  - OBJECTIVE: In the present study we compared the levels of CA-125, CA 19-9, and CA
      15-3 in the peritoneal fluid (PF) of patients with and without endometriosis,
      then assessed the possibility of a correlation among these tumor markers. STUDY
      DESIGN: Our study was a controlled clinical study of patients undergoing
      laparoscopy for infertility or other benign gynecology conditions. Peritoneal
      fluid samples were collected from 65 women with endometriosis and 43 women
      without pelvic disease. Levels of CA-125, CA 19-9 and CA 15-3 in the peritoneal
      fluid were determined by immunoradiometric assay. RESULTS: The concentration of
      CA-125 in PF from patients with endometriosis was significantly higher than that
      in the control group (p<0.001); for CA 19-9 and CA 15-3, PF concentrations were
      not statistically different between these two groups. Women with endometriosis
      had significantly higher levels of CA-125 in proliferative and secretory phases
      than the control group (p<0.001 and p<0.002 respectively); furthermore, in
      patients with endometriosis the CA 19-9 levels were significantly lower in
      secretory phase than the proliferative (p<0.004). The levels of CA-125 were
      significantly lower in women with tubal ligation, in comparison with infertility
      or pelvic pain in the control group (p<0.001). No significant difference was seen
      in women with infertility or pelvic pain in endometriosis group and the levels of
      CA-125, CA 19-9, and CA 15-3. We did not find any correlation between the stages
      of endometriosis and the concentration of CA-125, CA 19-9 and CA 15-3. A
      significant correlation between the CA 19-9 levels and CA 15-3 in patients with
      endometriosis was found (r=0.72, p=0.001). CONCLUSIONS: We found high
      concentrations of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid of women
      with and without endometriosis in the Yale series. However, the levels only of CA
      125 were higher in women with endometriosis, but without diagnostic value. The
      role of simultaneously high concentrations of CA 19-9 and CA 15-3 in women with
      endometriosis needs to be explored further.

PMID- 15243758
TI  - Factors influencing the quality of life after burst fractures of the
      thoracolumbar transition.
AB  - INTRODUCTION: Dorsal stabilisation has represented the standard procedure for the
      treatment of burst fractures of the thoracolumbar spine for a long time, but in
      the last few years the combined dorsoventral stabilisation has gained in
      significance due to its higher mechanical stability. However, there are no data
      yet available indicating whether the patients benefit from the combined operation
      with regard to their postoperative quality of life and what the advantages are in
      comparison with the dorsal procedures. Therefore, the question was researched in
      the framework of a matched-pairs analysis of patients suffering from an unstable
      fracture of the thoracolumbar transition. MATERIALS AND METHODS: From a
      consecutive series of patients treated in our clinic between 1995 and 2000, 10
      patients with combined and 10 patients with a purely dorsal stabilisation were
      selected and included in the study. Their quality of life was summed up in
      retrospect with the SF-36 questionnaire. The X-rays were analysed, and the Cobb
      angle as well as the sagittal index were calculated. Only patients with burst
      fractures of the thoracolumbar transition without accompanying co-morbidity and
      neurological deficits were included in the study. Both of the treated groups were
      matched with regard to sex, age and radiological patterns of injury. RESULTS:
      Patients who had undergone only a dorsal stabilisation showed a significant loss
      of correction according to the sagittal index at the time of the examination
      (0.88+/-0.02 postoperative vs 0.77+/-0.03 at 4 years postoperatively, p=0.01). In
      the group of patients treated with the combined therapy, there was no
      statistically relevant loss of correction with regard to the sagittal vertebral
      profile. The SF-36 questionnaire showed a reduced quality of life in both groups
      compared with an age-referenced norm population, especially concerning the
      parameters of bodily health. No statistically relevant difference was observed
      between the two groups. Further, there was no statistically relevant association
      between the parameters of the SF-36 and the clinical and radiological data. After
      performing several regression analyses it could be shown that the patient's
      mental health is a strong predictor of the postoperative vitality (r=0.803,
      p<0.01). However, none of the remaining parameters was able to predict the
      postoperative quality of life. CONCLUSION: The patients in this study showed a
      reduced quality of life, independent of the method of surgical treatment.
      Although better radiological results could be seen for the combined procedure,
      regarding the postoperative quality of life no advantage could be proved compared
      with the dorsally stabilized patients. Furthermore, there was no relation between
      the radiological results and the quality of life parameters. Therefore, it can be
      assumed that the injury itself seems to be the main cause of the decreased
      quality of life after a burst fracture of the thoracolumbar transition.

PMID- 15243760
TI  - Demyelinating peripheral neuropathy associated with hemophagocytic
      lymphohistiocytosis. An immuno-electron microscopic study.
AB  - We report the case of an 11-year-old male who developed subacute diffuse
      polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus
      infection. Parental consanguinity was present. The laboratory findings including
      bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH).
      Electrophysiological study of peripheral nerves revealed an intense and diffuse
      demyelinating process. The histological nerve lesions were severe and purely
      demyelinating. Most axons were intact. There was a diffuse infiltration of the
      nerve parenchyma by mononuclear cells. Immuno-electron microscopic study
      evidenced entry of macrophages into Schwann cell cytoplasm with dissociation of
      myelin sheaths. This boy died several months after the onset of the neuropathic
      symptoms. HLH is a rare genetic or acquired disorder in childhood characterized
      by abnormal immune activation, which induces an uncontrolled inflammatory
      response with sustained hyperactivation of T lymphocytes and macrophages. Only
      very rare cases of peripheral nerve involvement have been described in HLH. This
      is the first case showing that peripheral nerves, as other viscera, may be
      destroyed by the macrophagic infiltration, which characterizes HLH.

PMID- 15243759
TI  - Long gamma nail in the treatment of subtrochanteric fractures.
AB  - INTRODUCTION: The purpose of our study was to retrospectively evaluate the
      clinical and radiological results of subtrochanteric fractures treated with a
      long gamma nail (LGN). The LGN has been the implant of choice at our level-1
      trauma center since 1992. MATERIALS AND METHODS: Over a period of 7 years, we
      have treated 90 consecutive patients with subtrochanteric fractures. In order to
      evaluate the clinical and radiological outcomes, we reviewed the clinical and
      radiographic charts of these patients followed for a mean time of 2 years (range
      13-36 months). RESULTS: We found no intra- or perioperative complications nor
      early or late infection. Clinical and radiological union was achieved at a mean
      of 4.3 months in all of the patients (range 3-9 months); in 24 cases (30%) the
      distal locking bolts were retrieved in order to enhance callus formation and
      remodeling as a planned secondary surgery. Three patients (3.3%) needed unplanned
      secondary surgery for problems related to the nailing technique. Two mechanical
      failures with breakage of the nail were encountered due to proximal varus
      malalignment, of which one was treated with exchange nailing and grafting and the
      other one by removal of the broken hardware, blade-plating, and bone grafting.
      One fracture below a short LGN was treated by exchange nailing. CONCLUSIONS: The
      minimally invasive technique and simple application of the LGN lead to a low
      percentage of complications in these difficult fractures after a relatively short
      learning curve. The biomechanical properties of this implant allow early
      mobilization and partial weight-bearing even in patients with advanced
      osteoporosis.

PMID- 15243761
TI  - [Obesity and cardiovascular diseases-theoretical background and therapeutic
      consequences].
AB  - In the normal population, the prevalence of obesity is almost 20%. It is a
      condition influenced by genetic factors, so that individual behavior cannot be
      regarded as its sole cause. The amount of food is essentially determined by the
      hormone leptin, the feedback regulation of which can be disturbed by a
      modification of the molecule or a mutation of the receptor. A further important
      determinant is energy consumption, which is subject to large individual
      variations, which partly result from thermogenesis. With regard to the fat
      distribution, it is concentrated on the trunk in the android form as compared to
      the hips in the gynecoid form. The android form is subject to a higher incidence
      of cardiovascular morbidity and mortality. The indirect determination of body fat
      by measuring the body mass index (weight [kg]/body weight [m(2)]) is hence less
      reliable than measuring the waist (women > 80 cm, men > 94 cm). The effects of
      generalized obesity on cardiovascular function are chiefly an increase of blood
      volume and an eccentric left ventricular hypertrophy. This first of all results
      in diastolic dysfunction, which can give rise to a disturbance of systolic
      function in left ventricular dilatation. Concentric hypertrophy develops in the
      presence of arterial hypertension. This is twice as frequent in obese patients
      than in the normal population, which is due to increased activity of the
      sympathetic nervous system and stimulation of the renin-angiotensin system. A
      disturbance of lipid metabolism is observed four to six times more frequently.
      The qualitative change in LDL fraction with a raised concentration of low density
      LDL particles appears to be of crucial importance. With increasing fat mass, the
      sensitivity to insulin is lowered, so that in obesity the risk of developing
      diabetes mellitus type 2 is tripled. Since there has been a dramatic increase in
      the numbers of overweight children and adolescents (from 10.5% to 15.5% within
      the past five years), prevention programs should be started in good time. A
      reduction in calorie intake and an altered dietary composition (55% complex
      carbohydrates, 30% fat and 15% to 20% protein) on the one hand, and increased
      physical activity on the other hand continue to be the central components. The
      latter is especially effective when it regularly gives rise to an increased
      turnover of fatty acids as a result of an increased energy metabolism at moderate
      intensity. This leads to adaptation, i. e. an increase in the activity of
      lipoprotein lipase. If prevention programs and/or changes in lifestyle do not
      give rise to the desired weight reduction, medication is indicated in some
      adults. Sibutramine (Reductil and orlistate (Xenical) lead to an additional
      weight loss of up to 10%. However, consistent treatment of any cardiovascular
      risk factors present is more important. Treatment of arterial hypertension is of
      greatest prognostic significance, especially in concomitant diabetes mellitus. In
      individual cases and after thorough discussion of indication surgical options
      should be considered.

PMID- 15243762
TI  - [Minimally invasive quantitation of myocardial microvascular function using
      computed tomography: the blood volume-to-flow relationship].
AB  - The intramyocardial coronary microvasculature has an important role in regulating
      regional myocardial perfusion. Pathologic alterations of microvascular function
      may be present in early stages of coronary artery disease, myocardial
      hypertrophy, cardiomyopathy or systemic diseases such as arterial hypertension
      and diabetes mellitus. Fast computed tomography permits noninvasive simultaneous
      quantitation of regional intramyocardial blood volume and myocardial perfusion
      using indicator dilution principles. Our data indicate that especially the blood
      volume-to-flow relationship is sensitive enough to characterize and quantitate
      the functional impact of different pathologies along the coronary tree on
      microvascular function. This could be demonstrated for 1) acute impairment of
      microvascular function following coronary microembolization, 2) endothelial
      dysfunction induced by chronic hypercholesterolemia, 3) chronic epicardial non
      significant stenoses, 4) physiologic maturation of the normal microvasculature
      and 5) quantification of heterogeneity of microvascular function. These findings,
      the methodological background and the concept itself are presented in this
      article. Application of the blood volume-to-flow relationship is not limited to
      fast-CT but may be used in any cross sectional imaging technique, such as MRI or
      echocardiography, as long as intramyocardial blood volume and perfusion can be
      quantitated simultaneously. This new noninvasive approach to the quantification
      of intramyocardial microvascular function may prove a useful adjunct to those
      imaging techniques that are used to noninvasively quantitate epicardial stenoses
      or regional wall motion abnormalities.

PMID- 15243763
TI  - Escape from cardiomyocyte apoptosis by enterovirus persistence due to elevated
      soluble Fas-receptors.
AB  - BACKGROUND: Apoptosis causes loss of contractile cardiomyocytes in inflammatory
      heart disease. Despite recent examinations, the influence of virus infection on
      apoptosis remained ill-defined. METHODS: Apoptosis was assessed in left
      ventricular endomyocardial biopsies by the TUNEL method frompatients with chronic
      myocarditis and adeno-, cytomegalo- and enterovirus persistence. Soluble Fas
      ligands, sFas-receptors, TNF-alpha, IL-6, IL-10 and IFN-gamma were measured using
      ELISA technique. RESULTS: Elevated (P < 0.05) rates of apoptosis were found in
      patients with autoimmune myocarditis. Apoptosis was increased (P < 0.05) in the
      case of cytomegalovirus persistence, but not significantly increased in the
      presence of adenoviral genome. No evidence for apoptosis, but elevated
      concentrations of soluble Fas-receptors were found only in the case of
      enterovirus persistence. In turn, elevated percentages of apoptosis and normal
      soluble Fas-receptor concentrations were found in patients with chronic
      myocarditis. Serum levels of soluble Fas-ligands, TNF-alpha, IL-6, IL-10 and IFN
      gamma did not predict changes in TUNEL-positivity. CONCLUSIONS: Escape mechanisms
      to protect cardiomyocytes from apoptosis are yet not known for enterovirus
      infections. Soluble Fas-receptors have to be considered to counteract binding of
      soluble Fas-ligands that results in the blockade of apoptosis induction. It is a
      new finding that soluble Fasreceptors were elevated in the presence of
      enterovirus genome in the heart. Inhibition of apoptosis can impair virus
      clearing and prolong its replication with a potential worse outcome. In turn,
      sufficient protection from apoptosis in autoimmune myocarditis should reduce loss
      of cardiomyocytes. Therefore, the interaction of the Fas components could provide
      a new therapeutic target in myocarditis.

PMID- 15243764
TI  - Propranolol inhibits IK(Ado) by competitive A1-receptor interaction.
AB  - OBJECTIVES: Betablocking agents are known to exert anti-arrhythmic effects in
      ischemic myocardium due to blockade of myocardial beta-1-receptors. Since
      adenosine (Ado) induced muscarinic potassium current (IK(Ado)) and ATP sensitive
      potassium current (IK(ATP)) are discussed to be activated during ischemia we
      studied the effect of propranolol on IK(Ado) and IK(ATP). METHODS AND RESULTS:
      The effect of propranolol on muscarinic potassium current and IK(ATP) was studied
      in isolated rat atrial myocytes by means of the whole-cell voltage clamp tech-
      nique. Propranolol (50 microM) completely inhibited IK(Ado). IC50 was 7 microM.
      Inhibition of acetylcholine induced current (IK(ACh)) and GTP-gamma-S induced
      muscarinic potassium current was less potent (IC50 29 microM and 31 microM
      respectively). Propranolol was active from the outside only. Intracellular
      application did not significantly affect muscarinic potassium current. (+)
      propranolol, an isomer without beta-blocking properties, was as effective as (+/
      )-propranolol. The inwardly rectifying potassium current IK(ATP) showed minor
      sensitivity to the compound (10% current reduction, propranolol 50 microM).
      CONCLUSIONS: Propranolol inhibits IK(Ado). Inhibition is not due to beta-receptor
      blockade. Predominantly an interaction with A1-receptors seems to be involved.
      The observations in part might explain the anti-arrhythmic properties of the drug
      in ischemic/fibrillating myocardium based on the prolongation of refractoriness.

PMID- 15243765
TI  - Can serum NT-proBNP detect changes of functional capacity in patients with
      chronic heart failure?
AB  - Recently, in a cross-sectional study, a correlation of moderate degree was
      documented between serum BNP (brain natriuretic peptide) and exercise capacity in
      patients with chronic heart failure (CHF). However, it remains unknown if BNP,
      which increases in response to high myocardial wall stress, is sufficiently
      sensitive for changes in exercise capacity during clinical follow-up. To
      elucidate this, 42 CHF patients were recruited and randomized into a training (T;
      58 +/- 10 years; n = 14 NYHA II; n = 5 NYHA III) and a control group (CO; 54 +/-
      9, n = 17 NYHA II; n = 6 NYHA III). T carried out 12 weeks of endurance training
      on a cycle ergometer (4 sessions per week, 45 min duration). Venous blood
      sampling and cycle ergometry with simultaneous gas exchange measurements were
      carried out prior to and after the experimental phase. Due to its superior
      stability during laboratory procedures, NTproBNP was determined instead of BNP.
      Both proteins are secreted in equimolar amounts and share an identical diagnostic
      meaning. In both groups, NT-proBNP decreased slightly (T: from 1092 +/- 980 to
      805 +/- 724 pg x ml(-1); CO: from 1075 +/- 1068 to 857 +/- 1138 pg x ml(-1); T vs
      CO: p = 0.65). Anaerobic threshold (AT) as a measure of exercise capacity went up
      in T (from 0.96 +/- 0.17 to 1.10 +/- 0.22 l x min(-1)) but remained almost
      constant in CO (pre: 1.02 +/- 0.27; post: 1.00 +/- 0.27 l x min(-1); T vs CO: p <
      0.001). The correlation between changes in NT-proBNP and changes in AT remained
      insignificant (r = 0.02, p = 0.89)-even if only T was considered (r = 0.09, p =
      0.72). Improved exercise capacity in CHF patients due to 3 months of endurance
      training is not reflected in the course of NT-proBNP. These findings are
      inconsistent with a sufficient sensitivity of this parameter to detect changes in
      exercise capacity during clinical follow-up. Changes in NT-proBNP beyond its
      spontaneous variability are more likely to be detected following therapeutical
      interventions which aim more clearly at the myocardium. In determining
      alterations of functional capacity ergometric testing cannot be replaced by
      serial determinations of NT-proBNP.

PMID- 15243766
TI  - [Severe, non-infectious mitral valve endocarditis after mitral valve
      reconstruction in a 32-year old female with primary antiphospholipid syndrome].
AB  - BACKGROUND: A 32-year old female with primary antiphospholipid syndrome presented
      8 months after mitral valve reconstruction with progressive exertional dyspnea
      and echocardiographically demonstrable critical mitral stenosis and
      regurgitation. Tachycardia, weight loss, sleep disturbances and increasing
      nervosity led to the diagnosis of concomitant hyperthyroidism. After the patient
      stopped the oral anticoagulation by herself, a 'catastrophic antiphospholipid
      syndrome' with multiple microthromboembolic events in several organs developed
      rapidly within a few weeks. Severe respiratory failure was observed 14 days after
      admission at our hospital because of a pulmonary edema. TREATMENT: Removal of the
      annuloplasty ring and alloplastic mitral valve replacement with a 25 mm bilifleat
      valve. Postoperatively, the patient was placed on oral anticoagulation. Several
      pre- and postoperative plasmaphereses lowered the level of antiphospholipid
      antibodies. The patient additionally underwent radioiodtherapy 5 months
      postoperatively. RESULTS: While hemodynamics and diuresis remained sufficient,
      ventilatory support with tracheostomy was necessary for 16 postoperative days to
      achieve stable respiration. Thirty months later, the patient is well and without
      further cardiac and neurological dysfunction. CONCLUSION: Secondary cardiac valve
      operations on patients with primary antiphospholipid syndrome may be successfully
      performed within a multidisciplinary approach. Oral anticoagulation remains the
      treatment of choice to prevent further thromboembolic events.

PMID- 15243767
TI  - Combined transhepatic and transjugular approach for radiofrequency ablation of an
      accessory pathway in a child with complex congenital heart disease.
AB  - We report on a boy with recurrent drug resistant atrioventricular reentrant
      tachycardia. The patient had complex structural heart disease consisting of right
      atrial isomerism, systemic venous anomaly (mirror image orientation of the
      intrathoracic veins, hemiazygos continuation to the left-sided superior vena
      cava, with separate drainage of the hepatic veins into the left-sided atrium,
      congenitally corrected transposition (ccTGA), pulmonary atresia (PA), ventricular
      and atrial septal defects (VSD and ASD). At the age of 22 months RF ablation was
      performed. Access to the heart was obtained by percutaneous puncture of a hepatic
      vein, the left internal jugular vein, and femoral artery. Earliest retrograde
      atrial conduction during tachycardia was localized to the free wall of the left
      sided AV groove, and ablation in this area was successful. There were no
      procedure-related complications. RF ablation of accessory pathway is feasible in
      young children with complex structural heart disease and abnormal systemic venous
      return. In such patients access to the heart must be planned with the knowledge
      of the anatomy and judicious use of the hepatic venous approach, which should be
      done only by experienced investigators.

PMID- 15243768
TI  - Acute sialadenitis after percutaneous coronary intervention.
AB  - A 63 year old woman developed a swelling of the submandibular glands following
      PTCA. An ENT specialist made the presumptive diagnosis of viral sialadenitis. The
      submandibular swelling subsided completely within 48 hours. Sialadenitis is a
      rare side effect of ionic and nonionic radiocontrast agents. The pathogenic
      mechanism is not known. The swelling is self-limited with an excellent prognosis
      without specific therapy.

PMID- 15243769
TI  - Postcardiac injury syndrome following radiofrequeny ablation of atrial flutter.
AB  - We report the case of a 64-year-old woman who was admitted to our hospital for
      radiofrequency ablation of isthmus-dependent counterclockwise atrial flutter.
      Following an initially uncomplicated right atrial linear isthmus ablation that
      was associated with conversion of atrial flutter to sinus rhythm and evidence of
      complete isthmus block, the patient developed a small pericardial effusion, a
      marked and recurrent left-sided pleural effusion, and had significantly elevated
      inflammatory markers. After an extensive diagnostic work-up which excluded
      infectious, malignant and thromboembolic causes of the effusions, a diagnosis of
      postcardiac injury syndrome was made and the patient was treated with oral
      corticosteroids and nonsteroidal anti-inflammatory drugs. Over a treatment period
      of 2 months there was complete resolution of the pericardial and left-sided
      pleural effusions and normalization of inflammatory markers. Postcardiac injury
      syndrome is a rare complication of radiofrequency ablation that is characterized
      by signs of pericardial, pleural and pulmonary parenchymal inflammation.

PMID- 15243770
TI  - [Restrictive cardiomyopathy in childhood].
AB  - Restrictive cardiomyopathy is a rare heart muscle disease in childhood. By
      presenting a case report of a 15 year old adolescent, the aim of this article is
      to describe diagnosis, pathogenesis and therapy of restrictive cardiomyopathy. A
      review of the literature comprising pediatric studies on restrictive
      cardiomyopathy serves as a basis to discuss recommendations for therapeutic
      strategies in pediatric patients with this rare disease.

PMID- 15243772
TI  - Comments on "Investigation of intra-abdominal esophagus and hiatus in fetal rats
      with esophageal atresia and tracheo-esophageal fistula".

PMID- 15243773
TI  - Comment on stable postoperative biliary patients.

PMID- 15243774
TI  - Elastic bandaging for a ventral hernia.

PMID- 15243775
TI  - Acute retention of urine due to prolapsing stoma in a case of anorectal
      malformation with bladder neck fistula.
AB  - This case report describes an extremely premature infant who was born with a high
      anorectal malformation requiring a colostomy soon after birth. He later developed
      multiple episodes of acute urinary retention complicated by bilateral
      hydronephrosis and acute renal failure. The cause of the retention was found to
      be the prolapsing stoma, which was kinking the bladder neck.

PMID- 15243776
TI  - Esophageal replacement in children by an isoperistaltic gastric tube: a 12-year
      experience.
AB  - The colonic segment is the most frequently used material for replacing the
      esophagus in children; however, the use of a gastric tube has become a reliable
      alternative operation. Since 1987, we have used an isoperistaltic gastric tube to
      replace the esophagus in children, and we present a series of 21 patients.
      Indications for operation included caustic injury (nine), esophageal atresia
      (eight), peptic stricture (two), congenital stricture (one), and esophageal
      duplication (one). There was no death or necrosis of the graft during the early
      postoperative period. The esophagogastric anastomosis leaked in two cases, but
      both of them closed spontaneously. A temporary dumping syndrome was encountered
      in two children. Two patients had strictures of their upper anastomosis
      responding to dilatations. The two patients who had a pharyngogastric anastomosis
      developed either intractable stricture or nonfunctioning anastomosis. One of them
      died 9 months later from aspiration pneumonitis. At follow-up, 16 of 21 patients
      could accept a normal diet (13 were entirely asymptomatic, and three suffered
      occasional mild dysphagia). Two patients suffered significant dysphagia (one had
      a durable dilation of his gastric tube), and three needed a feeding jejunostomy.
      Acid secretion of the gastric tube was proved in nine cases. Two patients were
      shown to have cervical Barrett's esophagus above the anastomosis. These findings
      indicate the need for lifelong endoscopic follow-up for these patients.

PMID- 15243777
TI  - Intraoperative colonic lavage in infants using a Replogle tube.
AB  - On-table colonic lavage for preparing obstructed bowel prior to anastomosis or
      stoma formation is now routine in adults, but it is seldom used in paediatric
      practice. We describe a simple technique for intraoperative colonic lavage using
      inexpensive medical devices that are also readily available and disposable, a
      Replogle tube, a fine-bore sucker, and a 20-ml syringe. We have used this
      technique in infants with intestinal obstruction due to anorectal malformations,
      intestinal atresias, and post-NEC strictures, to good effect.

PMID- 15243779
TI  - Strengths and Difficulties Questionnaire (SDQ)--evaluations and applications.

PMID- 15243778
TI  - Molecular modeling of the interleukin-19 receptor complex. Novel aspects of
      receptor recognition in the interleukin-10 cytokine family.
AB  - The interleukin-10 (IL-10) cytokine family consists of several viral and human
      homologs that exhibit distinct receptor binding specificities. In the present
      study, the complex between interleukin-19 (IL-19) and its physiological receptor
      the interleukin-20 receptor alpha-chain (IL-20R1)-was modeled. The most prominent
      feature of this complex is an extended binding interface formed by a long loop of
      IL-20R1 and a bulge region of IL-19. The two regions exhibit complementary
      charges and have no structural counterparts in the IL-10/IL-10R1 complex but show
      some resemblance to the complex between interferon-gamma (IFN-gamma) and its
      receptor. Sequence comparison of the three cytokines (IL-19, IL-20, IL-24) that
      bind the IL-20R1 reveals a considerable conservation of the length of the
      interacting loops. One residue suggested to play a key role in receptor binding
      specificity is a conserved glutamate. The binding interface of IL-20R1 is rich in
      aromatic residues while the interfaces of its cytokine ligands are mainly formed
      by more flexible aliphatic amino acids. This structural feature might play an
      important role for the specific recognition of a single receptor chain by three
      different cytokines. [Figure: see text]. Comparison of the ligand/receptor
      interfaces in theA IL-10/IL-10R1,B IL-19/IL-20R1 andC IFN-gamma/receptor
      complexes. The translucent Connolly surfaces of the receptor and the ligand are
      shown in yellow and white, respectively. The backbone of the receptor and ligand
      are highlighted by a red and blue/green tube, respectively. For clarity, only one
      domain of the intertwined dimes is shown for IL-10 and IFN-gamma. Arrows denote
      the location of helix B and the corresponding structural elements in IL-19 and
      IFN-gamma as well as the location of receptor loop L2. As evident fromB andC an
      extended interaction surface is created in the IL-19/IL-20R1 and IFN
      gamma/receptor complexes by the interaction of this structural element with a
      long loop of the respective receptor.

PMID- 15243780
TI  - Normative data and scale properties of the German parent SDQ.
AB  - BACKGROUND AND OBJECTIVES: The Strengths and Difficulties Questionnaire (SDQ) is
      a short assessment instrument which addresses positive and negative behavioural
      attributes of children and adolescents and generates scores for clinically
      relevant aspects. Although this brief questionnaire has been widely used in
      Germany to gather information from parents, teachers, and older children
      themselves, normative results obtained with the German version have not yet been
      reported to the international scientific community. To allow comparisons with SDQ
      findings in other countries, normative data for the German parent-rated form as
      well as a community-based evaluation of scale properties are summarised and
      complemented by results obtained in a number of clinical samples. METHODS: Parent
      ratings were collected for a community-based sample of 930 children and
      adolescents aged between 6 and 16 years, in which both genders and all age levels
      were equally represented. Statistical evaluation of psychometric properties
      included a factor analysis verifying the proposed scale structure, assessment of
      scale homogeneities, and determination of age, gender and social class effects.
      Based on the distributions of SDQ scores observed in this normative sample,
      recommended bandings identifying normal, borderline, and clinical ranges were
      defined for each scale. RESULTS: Exact replication of the original scale
      structure, satisfactory internal reliabilities, and observation of the expected
      associations with age and gender confirmed the equivalence of the German SDQ
      parent questionnaire with the English original. Differences between community
      based results and clinical groups provided descriptive evidence of a dramatic
      impact of clinically defined psychiatric status on SDQ scores. CONCLUSIONS: After
      evaluating parent ratings obtained in a community-based sample, the German SDQ
      was shown to possess favourable psychometric properties. Thus, the German
      translation of this popular and versatile instrument seems to be a similarly
      reliable and useful assessment tool as the original English questionnaire.

PMID- 15243781
TI  - Validation of the parent and teacher SDQ in a clinical sample.
AB  - OBJECTIVES: This study examines whether the German translation of the Strengths
      and Difficulties Questionnaire (SDQ) is a reliable and valid screening instrument
      and whether it is as effective a tool for clinical diagnostics and scientific
      applications as the CBCL/TRF. METHODS: We examined 543 children and adolescents
      (147 girls and 396 boys) with ages ranging from 5 to 17 years and correlated the
      results of the parent and teacher SDQ as well as the CBCL/TRF with clinical
      diagnoses. Furthermore, the adequacy of the scale structure of the SDQ was tested
      using confirmatory and exploratory factor analyses. RESULTS: It was demonstrated
      that the scales of the parent and teacher versions were sufficiently homogeneous
      (0.72-0.83). Correlations between SDQ scales and corresponding CBCL/TRF scales
      showed a high degree of congruence, while an exact replication of the original
      SDQ scale structure could also be achieved. Parent and teacher versions of both
      questionnaires presented with good validity, not only with regard to the
      discrimination between child psychiatric patients and a representative community
      sample, but also in the identification of different categories of disorders
      within the clinical sample. CONCLUSION: The parent and teacher SDQs proved to be
      valid and helpful questionnaires for use in the framework of a multi-dimensional
      behavioural assessment, and appear to be well suited for screening purposes,
      longitudinal monitoring of therapeutic effects, and scientific research purposes.

PMID- 15243782
TI  - Evaluation of the self-reported SDQ in a clinical setting: do self-reports tell
      us more than ratings by adult informants?
AB  - OBJECTIVES: The aim of this study was to evaluate the German self-reported
      Strengths and Difficulties Questionnaire (SDQ) in a clinical setting. We also
      investigated whether this additional information gathered directly from older
      children and adolescents improves the prediction of clinical status when external
      ratings from their parents and/or teachers are already available. METHODS: SDQ
      self-reports were collected from 214 in- and outpatients (81 girls and 133 boys)
      aged 11 to 17 years who were seen at the department of child and adolescent
      psychiatry of the University of Gottingen. Results obtained with the self-rated
      questionnaire were compared with the parent and teacher SDQs, corresponding
      CBCL/YSR scores, and the clinical diagnostic classification. Finally, the
      additional diagnostic benefits of the self-reports were examined. RESULTS: The
      scales of the SDQ self-report proved to be sufficiently homogeneous, and
      acceptable correlations were found with the equivalent parent and teacher
      ratings. The self-rated version of the SDQ demonstrated good validity with
      respect to the differentiation between clinically defined cases and non-cases and
      in detecting various subcategories of psychiatric disorders within the clinic
      sample. SDQ self-reports significantly contributed to the prediction of
      diagnostic status, specifically if only parent or teacher ratings were available.
      CONCLUSIONS: The self-rated version of the SDQ was shown to be a reliable and
      valid method for the assessment of behavioural problems in children and
      adolescents. In the absence of adult informant reports from parents and teachers,
      the diagnostic value of self-ratings was also demonstrated.

PMID- 15243783
TI  - Using the Strengths and Difficulties Questionnaire (SDQ) multi-informant
      algorithm to screen looked-after children for psychiatric disorders.
AB  - BACKGROUND: Child psychiatric disorders are common among children in foster and
      residential care, but often go undetected and therefore untreated. AIMS: To
      assess the Strengths and Difficulties Questionnaire (SDQ) as a potential means
      for improving the detection of child psychiatric disorders in the community.
      METHOD: SDQ predictions and independent psychiatric diagnoses were compared in a
      community sample of 1,028 looked-after 5-17 year olds from a nationwide English
      survey. RESULTS: Multi-informant SDQs (parents, teachers, older children)
      identified individuals with a psychiatric diagnosis with a specificity of 80 %
      and a sensitivity of 85%. The SDQ prediction works best when SDQs have been
      completed by both carers and teachers. When it is only possible to have one adult
      informant, carers and teachers provide information of roughly equal predictive
      value. By contrast, self-reports by 11-17 year olds provide little extra
      information when there is already an adult informant. CONCLUSION: Using multi
      informant SDQs as a regular screening measure for looked-after children could
      potentially increase the detection of child psychiatric disorders, thereby
      improving access to effective treatments.

PMID- 15243784
TI  - The Strengths and Difficulties Questionnaire in the Nordic countries.
AB  - BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) has been
      translated into the different Nordic languages between 1996 and 2003. During the
      past few years, SDQs have been completed for nearly 100,000 children and
      adolescents in population-based studies as well as in clinical samples. The
      largest studies have been performed in Norway and Denmark, and in these countries
      the diagnostic interview DAWBA has also been used in conjunction with the SDQ.
      AIMS: In addition to a brief overview of past and ongoing SDQ work in Sweden,
      Finland, Norway, Denmark, and Iceland, we present scale means and standard
      deviations from selected community studies with comparable age groups, including
      parental reports for 7, 9 and 11 year-old children and self-reports of 13 and 15
      year-olds. CONCLUSIONS: The descriptive statistics suggest that the distributions
      of SDQ scores are very similar across the Nordic countries. Further collaborative
      efforts in establishing norms and evaluating the validity of the SDQ as a
      screening instrument are encouraged.

PMID- 15243785
TI  - The use of the Strengths and Difficulties Questionnaire (SDQ) in Southern
      European countries.
AB  - This paper reports a selection of completed or ongoing studies that have
      evaluated or applied the Strengths and Difficulties Questionnaire (SDQ) in five
      countries of Southern Europe: Italy, Spain, Portugal, Croatia, and France. In
      Italy, the SDQ has been used to study its concurrent validity with other norm
      based instruments (Child Behavior Checklist-CBCL and Disruptive Behavior Disorder
      Rating Scale-DBDRS), to assess the efficacy of a behavioural school training, and
      as part of an epidemiological study. In Spain, the SDQ was used to analyse the
      association between respiratory and other behavioural problems. In Portugal and
      Croatia, psychometric properties of the three versions of the SDQ (parent,
      teacher, and self-reports) were investigated in samples of children ranging from
      5 to 16 years. Past and ongoing studies in France have administered the SDQ to
      estimate inter-rater agreement between parents, teachers, and pupils, to carry
      out a large-scale epidemiological study, and to evaluate the efficacy of a parent
      training programme. In a second section, scale means obtained with the teacher
      version of the SDQ in three community-based samples of 7-8 year-old children from
      Italy, Portugal, and Spain are compared. The results show that, according to
      their teachers' ratings, Italian pupils showed less prosocial behaviour than
      their Spanish and Portuguese agemates, whereas the Portuguese children were rated
      as being more hyperactive and inattentive than comparable Italian and Spanish
      children. Possible causes underlying the observed differences between national
      SDQ means are discussed.

PMID- 15243786
TI  - The Strengths and Difficulties Questionnaire overseas: evaluations and
      applications of the SDQ beyond Europe.
AB  - BACKGROUND: During the few years that have passed since it became available, the
      Strengths and Difficulties Questionnaire (SDQ) has been extensively evaluated and
      widely applied to assess behaviour disorders of children and adolescents in
      European countries. In contrast, relatively few reports have published SDQ
      results obtained in other parts of the world, although its briefness and
      availability in over 40 languages make this instrument particularly attractive
      for international collaborations and cross-cultural comparisons concerning
      clinical and epidemiological issues. OBJECTIVES: This initial overview summarises
      some of these non-European experiences with the SDQ by presenting a selection of
      projects that have either psychometrically evaluated this novel questionnaire,
      applied it to screen for behaviour disorders, or employed its parent-, teacher-
      or self-rated versions as research tools. Since a large part of the mentioned
      studies are ongoing or have only recently been completed, much of the work
      reported here is still unpublished. CONCLUSIONS: Across a huge variety of
      cultures and languages, experience gained with the SDQ in other continents has
      supported European evidence of good psychometric properties and clinical utility
      of this questionnaire. Since worldwide usage of the SDQ can be expected to
      increase in the future, more international coordination is encouraged, in order
      to fully exploit the promising potentials of this versatile assessment tool and
      systematically investigate cross-cultural differences and similarities in child
      and adolescent behaviour.

PMID- 15243787
TI  - Effect of tooth-whitening strips and films on changes in color and surface
      roughness of resin composites.
AB  - Though the effectiveness of film and strip type tooth-whitening agents on the
      bleaching of tooth has been confirmed, there have been few studies on their
      influence on restorative materials. The purpose was to investigate the effect of
      tooth-whitening film and strip on the changes in color and surface roughness of
      dental resin composites. The composites used were Filtek Supreme (3M ESPE), Point
      4 (Kerr), and Spectrum TPH (Dentsply). Specimens were prepared 10 mm in diameter
      and 1 mm in thickness. Film type (Night Effect, Crest; Simply White Night,
      Colgate) and strip type (Whitestrips Professional, Crest; Claren, LG) agents were
      used, and bleaching procedures were performed for 2 weeks according to the
      manufacturers' recommendations. Color was measured according to the CIELab color
      scale with a spectrophotometer. Color difference ( DeltaE(*)(ab)) and surface
      roughness ( Ra) were measured. After bleaching, the DeltaE(*)(ab) values were
      0.90-1.67, which was too small to be perceptible (<3.3). The increase in Ra
      values was significant in some composite-whitening agent combinations ( P<0.01),
      however the value was less than 0.30 microm after bleaching. Therefore the change
      in surface roughness was clinically insignificant. We conclude that the influence
      of tooth-whitening film and strip on the color and surface roughness of dental
      resin composites was negligible.

PMID- 15243788
TI  - The activation of the [NiFe]-hydrogenase from Allochromatium vinosum. An infrared
      spectro-electrochemical study.
AB  - The membrane-bound [NiFe]-hydrogenase from Allochromatium vinosum can occur in
      several inactive or active states. This study presents the first systematic
      infrared characterisation of the A. vinosum enzyme, with emphasis on the spectro
      electrochemical properties of the inactive/active transition. This transition
      involves an energy barrier, which can be overcome at elevated temperatures. The
      reduced Ready enzyme can exist in two different inactive states, which are in an
      apparent acid-base equilibrium. It is proposed that a hydroxyl ligand in a
      bridging position in the Ni-Fe site is protonated and that the formed water
      molecule is subsequently removed. This enables the active site to bind hydrogen
      in a bridging position, allowing the formation of the fully active state of the
      enzyme. It is further shown that the active site in enzyme reduced by 1 bar H(2)
      can occur in three different electron paramagnetic resonance (EPR)-silent states
      with a different degree of protonation.

PMID- 15243789
TI  - A comparative, two-dimensional 14N ESEEM characterization of reduced [2Fe-2S]
      clusters in hyperthermophilic archaeal high- and low-potential Rieske-type
      proteins.
AB  - Proteins of the Rieske and Rieske-type family contain a [2Fe-2S] cluster with
      mixed ligation by two histidines and two cysteines, and play important roles in
      various biological electron transfer reactions. We report here the comparative
      orientation-selected ESEEM and HYSCORE studies of the reduced clusters from two
      hyperthermophilic Rieske-type proteins; a high-potential, archaeal Rieske protein
      called sulredoxin (SDX) from Sulfolobus tokodaii with weak homology to the
      cytochrome bc-associated Rieske proteins, and a low-potential, archaeal homolog
      of an oxygenase-associated Rieske-type ferredoxin (ARF) from Sulfolobus
      solfataricus. (14)N ESEEM and HYSCORE spectra of SDX and ARF show well-defined
      variations, which are primarily determined by changes of quadrupole couplings (up
      to 50% depending on the selected orientation) of the two coordinated nitrogens.
      These are due to variations in coordination geometry of the histidine imidazole
      ligands rather than to variations of hyperfine couplings of these nitrogens,
      which do not exceed 8-10%. The measured quadrupole couplings and their
      differences in the two proteins are consistent with those calculated using the
      reported crystal structures of high- and low-potential Rieske proteins. These
      results suggest that exploration of quadrupole tensors might provide a more
      accurate method for characterization of the histidine coordination in different
      proteins and mutants than hyperfine tensors, and might have potential
      applications in a wider range of biological systems.

PMID- 15243790
TI  - Is a single anterolateral screw-plate fixation sufficient for the treatment of
      spinal fractures in the thoracolumbar junction? A biomechanical in vitro
      investigation.
AB  - Controversy exists about the indications, advantages and disadvantages of various
      surgical techniques used for anterior interbody fusion of spinal fractures in the
      thoracolumbar junction. The purpose of this study was to evaluate the stabilizing
      effect of an anterolateral and thoracoscopically implantable screw-plate system.
      Six human bisegmental spinal units (T12-L2) were used for the biomechanical in
      vitro testing procedure. Each specimen was tested in three different scenarios:
      (1) intact spinal segments vs (2) monosegmental (T12/L1) anterolateral fixation
      (macsTL, Aesculap, Germany) with an interbody bone strut graft from the iliac
      crest after both partial corpectomy (L1) and discectomy (T12/L1) vs (3)
      bisegmental anterolateral instrumentation after extended partial corpectomy (L1),
      and bisegmental discectomy (T12/L1 and L1/L2). Specimens were loaded with an
      alternating, nondestructive maximum bending moment of +/-7.5 Nm in six
      directions: flexion/extension, right and left lateral bending, and right and left
      axial rotation. Motion analysis was performed by a contact-less three-dimensional
      optical measuring system. Segmental stiffness of the three different scenarios
      was evaluated by the relative alteration of the intervertebral angles in the
      three main anatomical planes. With each stabilization technique, the specimens
      were more rigid, compared with the intact spine, for flexion/extension (sagittal
      plane) as well as in left and right lateral bending (frontal plane). In these
      planes the bisegmental instrumentation compared to the monosegmental case had an
      even larger stiffening effect on the specimens. In contrast to these findings,
      axial rotation showed a modest increase of motion after bisegmental
      instrumentation. To conclude, the immobilization of monosegmental fractures in
      the thoracolumbar junction can be secured by means of bone grafting and the
      implant used in this study for all three anatomical planes. After bisegmental
      anterolateral stabilization a sufficient reduction of the movements was
      registered for flexion/extension and lateral bending. However, the observed
      slight increase of the range of motion in the transversal plane may lead to
      loosening of the implant before union. Therefore, the use of an additional dorsal
      fixation device should be considered.

PMID- 15243791
TI  - Fever in neutropenia in children and adolescents: evolution over time of main
      characteristics in a single center, 1993-2001.
AB  - GOALS OF WORK: To assess the evolution over time of main characteristics of
      episodes of fever in severe chemotherapy-induced neutropenia (FN) in children and
      adolescents with cancer treated for FN following nonmyeloablative chemotherapy,
      to compare the results with the experiences of other centers, and to assess the
      impact of the changes found on management of FN and on risk prediction rules.
      PATIENTS AND METHODS: Retrospective cohort study of all children and adolescents
      up to 18 years presenting with FN in a single pediatric oncology unit between
      1993 and 2001. MAIN RESULTS: In 132 patients, 364 episodes of FN were reported.
      The relative incidence of FN increased significantly over time in patients with
      precursor B-cell acute lymphoblastic leukemia (PBC-ALL), reflecting the increased
      intensity of chemotherapy. At presentation with FN, the proportions of patients
      (1) with PBC-ALL versus other malignancies, (2) with other malignancies being in
      complete remission, (3) with a central venous catheter, and (4) with shaking
      chills all significantly increased over time (overall proportions, 64%, 60%, 50%,
      and 5%, respectively; p <0.001 for all). In 337 (93%) episodes, ceftriaxone plus
      amikacin was used as empirical broad spectrum antimicrobial therapy. CONCLUSIONS:
      This study demonstrates that some characteristics of FN, though not necessarily
      its management, change over time, implying regular update of risk prediction
      rules. In contrast to other centers, the first-line antimicrobial therapy did not
      need modification because of changing resistance patterns.

PMID- 15243792
TI  - Lessons from an Ukrainian woman with clubbing and back pain.
AB  - We present this case that we consider of particular interest in palliative care
      because of the difficulty we encountered in palliating the patient's symptoms.
      The difficulties derived, at least in part, from particular personality traits
      and complex social circumstances. We think this case is an excellent example to
      demonstrate the complexity of the process of pain and the different resources and
      techniques that can be used to manage it. We also wish to underline the
      importance of clinical signs in diagnosis. In fact, this patient showed signs
      compatible with Pierre-Marie disease (or pulmonary hypertrophic osteoarthropathy,
      HOA). Finally, we would like to restate a possible link between neoplastic
      syndromes and the Chernobyl radiation disaster.

PMID- 15243793
TI  - Cytotoxic chemotherapy administered to two patients with partially refractory
      leukaemia while receiving intensive care treatment.
AB  - Administration of cytotoxic chemotherapy to a mechanically ventilated patient is
      a major undertaking. Induction of remission of leukaemia under such circumstances
      is an extremely rare event. We report two patients with partially refractory
      acute myeloid leukaemia who achieved remission of their leukaemia after receiving
      chemotherapy in the intensive care unit. Both patients were subsequently cured by
      allogeneic bone marrow transplant.

PMID- 15243794
TI  - [Psychological abnormalities in patients with complex regional pain syndrome
      (CRPS)].
AB  - QUESTION: Do comorbid psychological disorders, dysfunctional pain processing, and
      psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is
      a connection between clinical and psychological manifestations apparent? METHODS:
      In addition to securing information on case histories and performing clinical
      neurological examinations of chronic CRPS patients, the structured clinical
      interview (SCID), pain perception scale, and the Kiel Pain Inventory were
      employed. RESULTS: The structured clinical interview revealed evidence of a
      depressive episode in 65% of CRPS patients. Pain perception is similar to
      neuropathic pain syndromes and patient history revealed a slightly increased
      frequency of anxiety and affective disorders. Depressive syndrome occurred
      significantly more often in right-sided CRPS; otherwise, there were no
      significant correlations between medical history, clinical examination, and
      frequency of psychological disorders. However, CRPS patients with allodynia
      manifest clinical signs of special psychological distress. CONCLUSION: In chronic
      CRPS depressive syndrome frequently develops and psychological treatment can be
      recommended.

PMID- 15243795
TI  - Evidence that fungal pathogens inhibit recruitment of a shade-intolerant tree,
      white birch ( Betula papyrifera), in understory habitats.
AB  - Evidence from tropical forests suggests understory habitats are associated with a
      high risk of disease, which may prevent the establishment of vulnerable tree
      species; in contrast, canopy gaps can act as refuges from these pathogens.
      However, few studies have investigated the impacts of pathogens on regeneration
      in temperate forests. To determine whether losses to fungi of seeds of Betula
      papyrifera, a light-loving species, varied between habitats that differed in
      their degree of openness, we applied fungicide to seeds buried in old fields,
      treefall gaps, and forest understory sites. We found that the application of
      fungicide significantly reduced losses in all habitats, relative to control
      values. This effect was habitat-dependent: the benefit of fungicide was greater
      in forest understory than in openings. This suggests that B. papyrifera is
      prevented from establishing in understory environments in part by its
      susceptibility to pathogen attack, and not solely because of a high light
      requirement.

PMID- 15243797
TI  - Blood monocyte alteration caused by a hematozoan infection in the lizard Ameiva
      ameiva (Reptilia: Teiidae).
AB  - Although hematozoa have been described from many different host species, little
      is known about the infection and its relationship to the physiology of the host.
      We studied a hematozoan, regarded as a species of Lainsonia Landau, 1973
      (Lankestereliidae), which infects the monocytes of the lizard Ameiva ameiva. The
      infected animals show a huge monocytosis and morphological changes in the
      monocytes. Ultrastructurally, the parasite has an apical complex, dense bodies,
      electron lucent structures, plasma membrane projections and folding which may be
      involved with nutrition. The parasite occupies a parasitophorous vacuole (PV)
      exhibiting high electron density at its membrane. Mitochondria and the Golgi
      complex of the monocytes were concentrated around the PV, and the cytoplasm was
      totally occupied by a vimentin type of intermediate filament radiating from (or
      to) the cytosolic surface of the PV. Vimentin was identified by diameter
      measurement, immunofluorescence and immunoelectron microscopy. These observations
      indicate that this infection alters the physiological state of the host and
      suggest that this parasite has the ability to modify monocyte vimentin assembly.

PMID- 15243798
TI  - Immunohistochemical localisation of 3beta-hydroxysteroid dehydrogenase in
      Sarcocystis spp.
AB  - 3Beta-hydroxysteroid-dehydrogenase (3beta-HSD) is an isoenzyme that catalyses an
      essential step in the synthesis of all classes of active steroid hormones. The
      presence of steroid hormones of the vertebrate type in invertebrates is
      acknowledged in addition to a group of steroid-like hormones called ecdysteroids
      that were present in arthropods and helminths. In the present study, 3beta-HSD
      was detected in the bradyzoites enclosed in sarcocysts of Sarcocystis spp. with
      immunohistochemistry. The results suggest that self-originating steroid hormones
      may play important roles in the development of Sarcocystis spp., and possibly in
      the regulation of the reciprocal immune interaction between the host and these
      parasites.

PMID- 15243799
TI  - Cloning and characterization of the mitochondrial heat-shock protein 60 gene of
      Trichinella spiralis.
AB  - The full-length cDNA of mitochondrial heat-shock protein (hsp) 60 of the
      infective-stage larva of Trichinella spiralis was cloned by degenerative PCR and
      rapid amplification of cDNA end reactions. The 1,945 bp full-length cDNA sequence
      contained an open reading frame of 576 amino acids. A mitochondrial signal
      peptide was located at the N-terminal and a GGM motif at the C-terminal. The gene
      contained ten exons and nine introns. RT-PCR analysis indicated that thermal,
      cold, acidic and oxidative treatment did not elicit significant changes in the
      expression of mitochondrial hsp 60 in the larvae. Cluster analysis showed that
      the sequence of the hsp 60 gene of T. spiralis is closely related to that of
      Drosophila melanogaster.

PMID- 15243800
TI  - The usefulness of short-term in vitro cultivation for the detection and molecular
      study of Blastocystis hominis in stool specimens.
AB  - When in vitro cultivation was used as the 'gold standard' for the detection of
      Blastocystis hominis in stool specimens, simple smear and trichrome staining
      showed sensitivities of 16.7% and 40.2% and specificities of 94% and 80.4%,
      respectively. In vitro cultivation also enhanced PCR amplification for the
      detection of B. hominis in stool specimens. Our data show the usefulness of in
      vitro cultivation for the detection and molecular study of B. hominis in stool
      specimens.

PMID- 15243801
TI  - The antifilarial activity of a marine red alga, Botryocladia leptopoda, against
      experimental infections with animal and human filariae.
AB  - The antifilarial activity of the marine red alga Botryocladia leptopoda against
      rodent and human lymphatic filarial parasites is described. The animal filarial
      species included Litomosoides sigmodontis and Acanthocheilonema viteae maintained
      in cotton rats and Mastomys coucha, respectively, while a subperiodic strain of
      the human lymphatic filarial parasite Brugia malayi was maintained in M. coucha.
      The crude extract and its hexane fraction brought about a marked reduction in the
      peripheral microfilarial level in both of the rodent filarial parasites L.
      sigmodontis and A. viteae. The microfilaricidal effect began slowly from day 8 or
      15 after initiation of treatment and increased with time with a very high
      efficacy at the end of the observation period against both rodent filariids. The
      microfilaricidal efficacy was, however, not as prominent in the case of B.
      malayi. The antifilarial activity, which occurred in the hexane fraction, exerted
      action at a much lower dose. The product killed a significant proportion of A.
      viteae and L. sigmodontis adult parasites. In the case of B. malayi, although the
      macrofilaricidal efficacy was much less than that of the rodent parasites, it
      (hexane fraction) caused sterilization of a significant proportion of the
      surviving female parasites. The present findings indicate the possibility of
      developing an adulticidal and female sterilizing agent against filarial parasites
      from a marine red alga.

PMID- 15243802
TI  - Reduction in testosterone concentration and its effect on the reproductive output
      of chronic malaria-infected male mice.
AB  - An experimental host-parasite association involving BALB/c male mice infected
      with Plasmodium chabaudi chabaudi was used in order to investigate the influence
      of the parasite on the sexual physiology and behavior of infected hosts. Infected
      males displayed complete courtship behavior leading to ejaculation and sired
      litters on several occasions. A weekly assay of testosterone and corticosterone
      plasma concentrations revealed a twofold decrease in the testosterone level at 4
      and 5 weeks post-injection, during recrudescence. This imbalance was accompanied
      by a decrease in the overall duration of the social investigation contacts
      occurring during courtship and by a reduction in the fertilization rate of the
      infected animals. These physiological perturbations can be regarded as an
      adaptive response of the host to the recrudescing parasites, which illustrates
      the rodents' capacity for regulating the testosterone profiles needed to balance
      the competing demands of immunity and reproduction.

PMID- 15243803
TI  - The comparative development of Echinostoma caproni (Trematoda: Echinostomatidae)
      adults in experimentally infected hamsters and rats.
AB  - The aim of the present study was to compare the development of Echinostoma
      caproni (Trematoda: Echinostomatidae) adults in two host species displaying
      different degrees of compatibility with this parasite. For this purpose, the
      variability in the worm recovery, egg output, and morphology of E. caproni adults
      during the course of experimental infections in hamsters and rats was analyzed.
      Student's t-tests and two-factor ANOVA analysis with the time post-infection and
      the host species as independent variables, and Bonferroni t-tests as post hoc
      analysis were used for the study. Worm recovery and egg output were host species
      dependent. The values were significantly higher in the worms established in
      hamsters than those in rats. The oral sucker area, pre-pharynx length, and
      pharynx area were the most conservative features, and no significant variability
      related to the host species was detected. In contrast, body area, collar width,
      esophagus length, cirrus sac area, ventral sucker area, ovarian area and anterior
      and posterior testicular areas were significantly higher in those worms collected
      from hamsters. Moreover, significant worm age-host species interactions were
      found for body area, ovarian area, ventral sucker area, and anterior and
      posterior testicular areas.

PMID- 15243804
TI  - Differential proteomic analysis of human hepatocellular carcinoma cell line
      metastasis-associated proteins.
AB  - PURPOSE: The comparative study of differentially expression of protein profiles
      of hepatocellular carcinoma cell lines with various metastasic potential and
      screening key molecules related to hepatocellular carcinoma metastasis and
      recurrence. METHODS: Using two-dimensional electrophoresis and liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS),
      we analyzed differentially displayed proteomics of human hepatocellular carcinoma
      cell lines Hep3B, MHCC97L, MHCC97H with different metastasic potential. RESULTS:
      Approximate 1,000 protein spots were detected on silver-stained gel by
      ImageMaster (977+/-113 spots in Hep3B, 1092+/-40 in MHCC97L, and 889+/-14 in
      MHCC97H). Fifty distinct different protein spots were analyzed with online LC-ESI
      MS/MS. Only 26 protein spots had a positive result, including annexin1, S100A4,
      and so on. In comparison with nonmetastasis Hep3B cell lines, there were 16
      proteins overexpressed in MHCC97H and MHCC97L, 10 proteins underexpressed in
      MHCC97H and MHCC97L. Applying cell immunohistochemistry and RT-PCR, we further
      validated two interesting and different proteins, annexin1 and S100A4.
      CONCLUSION: The protein profile of metastatic hepatocellular carcinoma cell lines
      displayed obvious differences compared with non-metastatic liver cancer cell
      lines. The results imply that various different proteins may lead to HCC
      metastasis together.

PMID- 15243805
TI  - Potent antitumoral efficacy of a novel replicative adenovirus CNHK300 targeting
      telomerase-positive cancer cells.
AB  - PURPOSE: Telomerase reverse transcriptase (hTERT) is the key determinant of
      telomerase activity and plays a crucial role in cellular immortalization and
      oncogenesis. It will be a promising target for cancer gene therapy. We
      constructed a novel replicative adenovirus CNHK300 in which hTERT promoter with
      three extra E-boxes downstream of the promoter was introduced and used to
      regulate adenoviral E1a gene, and studied its properties of selective replication
      in cancer cells and antitumoral activity. METHODS: Luciferase assay was used to
      detect hTERT promoter activity. The selective replication of CNHK300 in cancer
      cells was investigated by E1a Western blot and green fluorescent protein (GFP)
      reporter gene assay. The antitumoral activity of CNHK300 and its toxicity were
      measured on animal models. RESULTS: Luciferase assay showed that introducing
      extra E-boxes downstream of hTERT promoter is beneficial to decreasing the
      promoter activity in normal cells without affecting its strong activity in cancer
      cells. Experiments in vitro and in vivo demonstrated that CNHK300 can selectively
      target to hTERT-positive cancer cells and replicate in them, resulting in
      oncolytic or antitumoral effect. CNHK300 is superior to ONYX-015 in terms of
      selective replication and oncolytic or antitumoral effect. The toxicity assay
      showed no signs of toxicity to liver cells even at the higher dosage of CNHK300
      in vivo. CONCLUSION: The hTERT promoter-controlled, replication-competent
      adenovirus CNHK300 is a promising system for targeted cancer gene therapy.

PMID- 15243806
TI  - Monitoring the clinical and biochemical response to enzyme replacement therapy in
      three children with Fabry disease.
AB  - Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting
      from a deficiency of the lysosomal enzyme alpha-galactosidase A. This leads to
      the progressive accumulation of glycosphingolipids in lysosomes of most visceral
      tissues and in body fluids. Following successful clinical trials in adults, two
      recombinant enzyme preparations of alpha-galactosidase have recently been
      licensed in Europe for the treatment of Fabry disease and treatment in children
      has commenced. We now report the clinical findings and the levels of
      globotriaosylceramide in plasma and urine in three boys who have been treated
      with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2
      years. In one boy there was a rapid improvement in all the clinical and
      biochemical parameters measured. This has been maintained. In the other two boys,
      who are siblings, there was no measurable clinical improvement after 1 year and
      the levels of globotriaosylceramide in plasma and urine, although lower than
      before treatment, were still considerably elevated. There was no evidence of
      blocking or neutralising antibodies so the dose of enzyme was increased to 2
      mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this
      was not accompanied by any reduction in the plasma or urine globotriaosylceramide
      levels. CONCLUSION: Measurement of globotriaosylceramide in plasma and urine may
      not be the most appropriate marker to monitor the progression of treatment by
      enzyme replacement therapy in all patients. Certainly the subjective clinical
      improvement in the two brothers in this report outweighed the objective
      biochemical findings.

PMID- 15243807
TI  - Nail dystrophy--a clinical sign of malnutrition in the disabled child.

PMID- 15243809
TI  - Langerhans histiocytosis, haemophagocytic syndrome and Epstein-Barr virus
      infection.

PMID- 15243808
TI  - Identical twin brothers concordant for Langerhans' cell histiocytosis and
      discordant for Epstein-Barr virus-associated haemophagocytic syndrome.
AB  - We report on identical twin brothers, one of whom presented at 14 months of age
      with fever and clinical, laboratory and histological evidence of Epstein-Barr
      virus-associated haemophagocytic syndrome (EBV-AHS) and 4 months later with
      typical signs and symptoms of Langerhans' cell histiocytosis (LCH). The other
      twin, without previous symptoms, also displayed at that time LCH associated with
      signs of recent EBV infection, but without symptoms of haemophagocytic syndrome.
      No mutation in the SH2D1A gene, as observed in X-linked lymphoproliferative
      disease, or in the perforin gene as observed in some cases of hereditary
      haemophagocytic syndrome, was found. CONCLUSION: the occurrence of
      haemophagocytic syndrome and Langerhans' cell histiocytosis, although genetically
      based, can be triggered by environmental agents and viruses, in particular
      Epstein-Barr virus.

PMID- 15243810
TI  - Hypothalamic adipic hypernatraemia syndrome with normal osmoregulation of
      vasopressin.
AB  - Adipsic hypernatraemia is an uncommon disorder in childhood caused by a defect in
      the osmoregulation of thirst, leading to impairment of water homeostasis and
      chronic hyperosmolality of body fluids. Adipsia is often associated with an
      abnormality in osmoregulated vasopressin secretion due to the close proximity of
      the hypothalamic osmoreceptors that control thirst with those regulating
      vasopressin secretion. Hypothalamic lesions of diverse aetiology (vascular
      abnormalities, neoplasms, granulomatous diseases, trauma etc.) have been
      described in this syndrome. We report a 12-year-old boy with evident weight loss
      due to hypernatraemic dehydration with a selective defect in osmoregulation of
      thirst and normal vasopressin secretion with no demonstrable structural lesion.
      To date, only six paediatric patients with this condition have been described in
      the literature. CONCLUSION: Hypothalamic adipsic hypernatraemia syndrome must be
      suspected when a dehydrated patient denies thirst. The study of antidiuretic
      function is necessary because the osmoregulation of vasopressin secretion could
      be altered.

PMID- 15243811
TI  - Steroid-sparing effect of tacrolimus in a patient with juvenile dermatomyositis
      presenting poor bioavailability of cyclosporine A.

PMID- 15243812
TI  - Rituximab in children with idiopathic thrombocytopenic purpura: does it really
      work?

PMID- 15243813
TI  - Recruitment of Hsp70 chaperones: a crucial part of viral survival strategies.
AB  - Virus proliferation depends on the successful recruitment of host cellular
      components for their own replication, protein synthesis, and virion assembly. In
      the course of virus particle production a large number of proteins are
      synthesized in a relatively short time, whereby protein folding can become a
      limiting step. Most viruses therefore need cellular chaperones during their life
      cycle. In addition to their own protein folding problems viruses need to
      interfere with cellular processes such as signal transduction, cell cycle
      regulation and induction of apoptosis in order to create a favorable environment
      for their proliferation and to avoid premature cell death. Chaperones are
      involved in the control of these cellular processes and some viruses reprogram
      their host cell by interacting with them. Hsp70 chaperones, as central components
      of the cellular chaperone network, are frequently recruited by viruses. This
      review focuses on the function of Hsp70 chaperones at the different stages of the
      viral life cycle emphasizing mechanistic aspects.

PMID- 15243814
TI  - Theoretical and numerical study of a bone remodeling model: the effect of
      osteocyte cells distribution.
AB  - It is well argued that osteocytes are mechanosensory cells and are involved in
      the regulation of bone remodeling. In previous works, the predictions from a
      simulation model have suggested that both the influencing distance of osteocytes
      and the magnitude of the mechanical loads determine the thickness of trabeculae
      whereas the number of osteocytes primarily affects the rate of bone remodeling.
      The question that remains not completely answered is: for the same number of
      osteocytes, what is the effect of different distributions on the remodeling
      process? Based on a particular regulatory bone remodeling model, the question is
      addressed, in part, by performing a stability analysis in connection with
      numerical simulations. The results allow us to demonstrate that, on one hand, we
      cannot reach a conclusion about the stability of the model for a nonuniform
      osteocyte distribution. This implies that there is no relationship between the
      different parameters conveying the stability of the model. On the other hand, we
      show that the osteocyte cell distribution has a significant influence on the bone
      morphology, which seems to be confirmed by simulations with real data obtained
      from rat tibia.

PMID- 15243815
TI  - Pre-treatment and post-treatment assessment of the C(6) test in patients with
      persistent symptoms and a history of Lyme borreliosis.
AB  - It was recently reported that antibody to C(6), a peptide that reproduces an
      invariable region of the VlsE lipoprotein of Borrelia burgdorferi, declined in
      titer by a factor of four or more in a significant proportion of patients after
      successful antibiotic treatment of acute localized or disseminated Lyme
      borreliosis. The present study evaluated the C(6) test as a predictor of therapy
      outcome in a population of patients with post-treatment Lyme disease syndrome.
      The serum specimens tested were from patients with well-documented, previously
      treated Lyme borreliosis who had persistent musculoskeletal or neurocognitive
      symptoms. All of the patients had participated in a recent double-blind, placebo
      controlled antibiotic trial in which serum samples were collected at baseline and
      6 months thereafter, i.show $132#e. 3 months following treatment termination. In
      this patient population no correlation was found between a decline of C(6)
      antibody titer of any magnitude and treatment or clinical outcome. Antibodies to
      C(6) persisted in these patients with post-treatment Lyme disease syndrome
      following treatment, albeit at a markedly lower prevalence and titer than in
      untreated patients with acute disseminated Lyme disease. The results indicate
      that C(6) antibody cannot be used to assess treatment outcome or the presence of
      active infection in this population.

PMID- 15243816
TI  - Relevance of genetically determined host factors to the prognosis of
      meningococcal disease.
AB  - To assess the relevance of genetically determined host factors for the prognosis
      of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis
      factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator
      inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with
      meningococcal disease and in 290 healthy controls matched by sex. Distribution of
      FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between
      patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or
      =1 point in the Barcelona prognostic system more frequently than patients with
      other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, P<0.0001),
      and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval,
      1.1-11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers
      of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

PMID- 15243817
TI  - Seroepidemiology of rubella in northern Greece.
AB  - In light of two rubella outbreaks in northern Greece during the last decade (1993
      and 1999) and periodic changes to the immunization strategy, the present study
      was conducted to determine the current status of rubella immunity in this region.
      Among the 729 subjects studied the total vaccination rate was 30.4% and the
      seroprevalence rate was 82.4% (odds ratio, 0.618; 95% confidence interval, 0.415
      0.921). A higher seroprevalence (83.2%) was observed among people born before
      1989, when the national rubella immunization program was introduced, compared to
      the individuals born after 1989 (67.1%; P=0.000). Among women of reproductive age
      (i.e. 16-40 years), who represented 69.6% of the study population, 10.3% were
      susceptible to rubella and only 16.4% were vaccinated. The results indicate a
      comprehensive policy is still needed in order to eliminate rubella and congenital
      rubella syndrome in Greece.

PMID- 15243818
TI  - Cultural issues skill.

PMID- 15243819
TI  - More impostors identified.

PMID- 15243820
TI  - 80-hour workweek-one solution.

PMID- 15243821
TI  - New research family medicine interest groups impact student interest.

PMID- 15243822
TI  - Conflict, collaboration and resolution.

PMID- 15243823
TI  - The CALMER approach: Teaching learners six steps to serenity when dealing with
      difficult patients.

PMID- 15243824
TI  - A problem-based approach to teaching outcomes research in family medicine
      residency.
AB  - OBJECTIVE: This study's objective was to introduce research concepts and skills
      in family medicine residency through a problem-based course. METHODS: Eight third
      year residents per year in 3 academic years participated. Groups of two-three
      were presented with the task of developing, executing, and reporting on a small
      research project within the family medicine clinic. RESULTS: Residents' research
      skills and attitudes toward research improved. The projects resulted in
      successful presentations to colleagues and submissions to national conferences
      and peer-reviewed journals. CONCLUSIONS: This problem- based approach to research
      education for family medicine residents is productive and enjoyable.

PMID- 15243825
TI  - Lessons from Andy.

PMID- 15243826
TI  - A walk (or run) in their shoes.

PMID- 15243827
TI  - Writing workshops for third-year residents.

PMID- 15243828
TI  - Factors associated with receiving hepatitis B vaccination among high-risk adults
      in the United States: an analysis of the National Health Interview Survey, 2000.
AB  - BACKGROUND AND OBJECTIVES: Although an effective vaccine against hepatitis B has
      been licensed in the United States since 1981, and successful childhood
      vaccination programs have been implemented, hepatitis B virus transmission
      continues to occur among high-risk adults. In this study, we identified factors
      associated with receipt of one or more doses of hepatitis B vaccine among adults
      at high risk for hepatitis B infection. METHODS: We analyzed data from the 2000
      National Health Interview Survey of selected adults ages 18-49 years who were at
      high risk for hepatitis B infection (n=1,036). Multivariable regression analysis
      was conducted to determine factors independently associated with vaccination.
      RESULTS: Although more than 80% (n=841) of high-risk adults reported previous
      visits to a clinician during the past year, only 30% (n=498) of men and 31%
      (n=538) of women reported having received a single dose of hepatitis B vaccine.
      Young age (18-29 years), never being married, past blood donation, and past human
      immunodeficiency virus (HIV) testing were independently associated with receiving
      vaccination for men. For women, young age (18-29 years) and previous vaccinations
      were significant factors associated with vaccination receipt. Additionally,
      having a primary care source (men) and seeing an obstetrician-gynecologist
      provider in the past year (women) were significantly associated with vaccination.
      CONCLUSIONS: Hepatitis B vaccination rates for high-risk adults are low, and
      missed opportunities are frequent. Additional strategies are needed to increase
      immunization rates of adults at high risk for hepatitis B.

PMID- 15243829
TI  - An evaluation of the care provided to patients prescribed controlled substances
      for chronic nonmalignant pain at an academic family medicine center.
AB  - BACKGROUND AND OBJECTIVES: Prescribing medications for chronic nonmalignant pain
      (CNMP) can be challenging for physicians for many reasons. In 1999, the state of
      Oregon implemented new guidelines governing the prescription of medications for
      CNMP. This study assessed the quality of care provided to CNMP patients,
      including the extent of compliance with the new state requirements 2 years after
      they were implemented. METHODS: We used telephone records to identify patients
      who had called for prescription refills between mid 2001 and mid 2002. We then
      reviewed medical records of those patients to identify those who received refills
      for opioids or benzodiazepines for treatment of chronic pain. Medical records
      were evaluated to measure the percentage of records exhibiting documentation of
      compliance with state prescribing laws and other features indicative of a high
      standard of care. RESULTS: Ninety seven percent of records included documentation
      of the diagnosis for which chronic therapy was indicated. Required Material Risk
      Notification Forms were absent from 100% of charts. Seventy-five percent of
      records document consultation with a pain specialist or other physician with
      specialty pertinent to the patient's source of pain. Medication contracts were
      only present in 39% of records, and documentation of a pain evaluation and
      functional evaluation was present in 67% and 54% of records, respectively.
      CONCLUSIONS: Review of medical records in our clinic documented less-than-optimal
      compliance with state laws regulating prescribing for CNMP and the need for
      improvement in assessment and care of these patients.

PMID- 15243830
TI  - Factors influencing cessation of pregnancy care in Oregon.
AB  - BACKGROUND AND OBJECTIVES: Anecdotal evidence suggests that many providers who
      previously delivered babies are no longer doing so, both in Oregon and
      nationally. This study determined the proportion of pregnancy care providers who
      have stopped or are planning to stop providing this care in Oregon and identified
      the important factors influencing such practice changes. METHODS: We mailed a
      survey in October and November 2002 to all obstetrician-gynecologists, family
      physicians, general practitioners, and certified nurse midwives practicing in
      Oregon. The survey inquired about whether they currently perform deliveries. If
      they did not do so, or if they did so but planned to stop, further questions were
      asked about reasons for not providing this care. RESULTS: A total of 2,158
      surveys were mailed; 1,232 were returned (58% adjusted response rate), and 1,069
      had sufficient information to be included in our analysis. Of respondents, 511
      (47.8%) currently perform deliveries. Of these, 157 (30.7%) indicated that they
      planned to stop doing so in 1 to 5 years, with cost of professional liability
      insurance (59%) and fear of lawsuits (43%) most frequently cited as major
      reasons. A total of 367 (34%) respondents had previously stopped performing
      deliveries. Providers who stopped providing this care since 1999 were
      significantly more likely to cite cost of medical liability insurance and low
      reimbursement as major reasons, compared to providers who stopped earlier.
      CONCLUSIONS: Our study suggests that as many as half of clinicians who previously
      performed or currently perform deliveries in Oregon are planning to stop or have
      already stopped providing this service, raising concern about access to pregnancy
      care services for women in the state.

PMID- 15243831
TI  - Audience response system: effect on learning in family medicine residents.
AB  - BACKGROUND AND OBJECTIVES: The use of an electronic audience response system
      (ARS) that promotes active participation during lectures has been shown to
      improve retention rates of factual information in nonmedical settings. This study
      (1) tested the hypothesis that the use of an ARS during didactic lectures can
      improve learning outcomes by family medicine residents and (2) identified factors
      influencing ARS-assisted learning outcomes in family medicine residents. METHODS:
      We conducted a prospective controlled crossover study of 24 family medicine
      residents, comparing quiz scores after didactic lectures delivered either as
      ordinary didactic lectures that contained no interactive component, lectures with
      an interactive component (asking questions to participants), or lectures with
      ARS. RESULTS: Post-lecture quiz scores (maximum score 7) were 4.25 +/- 0.28 (61%
      correct) with non-interactive lectures, 6.50 +/- 0.13 (n=22, 93% correct)
      following interactive lectures without ARS, and 6.70 +/- 0.13 (n=23, 96% correct)
      following ARS lectures. The difference in scores following ARS or interactive
      lectures versus non-interactive lectures was significant (P <.001). Mean quiz
      scores declined over 1 month in all three of the lecture groups but remained
      highest in the ARS group. Neither lecture factors (monthly sequence number) nor
      resident factors (crossover group, postgraduate training year, In-Training
      Examination score, or post-call status) contributed to these differences,
      although postcall residents performed worse in all lecture groups. CONCLUSIONS:
      Both audience interaction and ARS equipment were associated with improved
      learning outcomes following lectures to family medicine residents.

PMID- 15243832
TI  - A retrospective review of performance and utility of routine clinical pelvimetry.
AB  - BACKGROUND AND OBJECTIVES: Some authorities have questioned the utility of
      performing clinical pelvimetry as part of routine prenatal care. This study
      determined the frequency with which clinical pelvimetry is still performed at two
      military hospitals and whether the results of pelvimetry influence the management
      of labor and delivery. METHODS: We conducted a retrospective review of prenatal
      records at two military hospitals. One was an overseas hospital, and one was a
      family medicine teaching hospital in the United States. The records of 660
      pregnant women were reviewed to identify documentation that pelvimetry was
      performed during prenatal care and whether there was evidence that the physician
      managing labor and delivery altered management based on pelvimetry results.
      RESULTS: Seventy percent (461) of the 660 records reviewed had all pelvimetry
      measurements documented as normal, or the provider had written "good for TOL
      (trial of labor)," "proven to XX pounds," or similar annotation that pelvimetry
      was normal. Nine percent (58 records) had no documentation of pelvimetry
      (pelvimetry section left blank). The remaining 21% (141 charts) had at least one
      pelvimetry measurement listed as abnormal on the initial prenatal exam. No
      admission note, progress note, or operative note recorded during labor and
      delivery made reference to clinical pelvimetry results. No abnormal pelvimetry
      result was referenced in follow-up visits or appeared to make any difference in
      mode of delivery or treatment in labor. Two women (one at each institution) had
      initial visit notes indicating the need to consider radiographic pelvimetry based
      on the results of clinical exam, but this test was not done in either case, and
      both women delivered vaginally. CONCLUSIONS: Our study indicates that clinical
      pelvimetry does not change management of pregnant patients. Current practice is
      to allow all women a trial of labor regardless of pelvimetry results. This makes
      the routine performance and recording of clinical pelvimetry a waste of time, a
      potential liability, and an unnecessary discomfort for patients.

PMID- 15243833
TI  - Postoperative adverse events in teaching and nonteaching hospitals.
AB  - BACKGROUND AND OBJECTIVES: With the recent attention on quality of care and
      residency training, teaching hospitals are coming under greater scrutiny. Despite
      several studies, there is still no consensus on whether teaching hospitals
      deliver higher quality of care than nonteaching hospitals. METHODS: This was a
      retrospective cross-sectional study, using national hospital data. The sample
      consisted of 3,818 acute care hospitals in the National Inpatient Sample from
      1990-1996. The quality indicators were postoperative adverse events, including
      venous thrombosis/pulmonary embolism (DVT/PE), pulmonary compromise, pneumonia,
      and urinary tract infection (UTI). Hospitals were classified as major teaching,
      other teaching, and nonteaching. Quality indicator rates of hospital types were
      compared and multivariate regression performed to control for specific hospital
      characteristics. RESULTS: Teaching hospitals had higher rates of postoperative
      DVT/PE and pulmonary compromise but lower rates of UTI, compared with nonteaching
      hospitals. In the multivariate analysis, teaching hospitals were more likely to
      have higher postoperative DVT/PE rates, and other teaching hospitals had higher
      rates of pulmonary compromise and UTI. Postoperative pneumonia rates were higher
      in major teaching hospitals than nonteaching hospitals. CONCLUSIONS: Rates of
      postoperative adverse events were higher in teaching hospitals compared to
      nonteaching hospitals. These findings suggest that quality of care, as measured
      by postoperative adverse events, may not be higher in teaching hospitals.

PMID- 15243834
TI  - Health fair screening: the clinical utility of the comprehensive metabolic
      profile.
AB  - BACKGROUND AND OBJECTIVES: Health fairs are a common method used by providers and
      health care organizations to provide screening tests, including comprehensive
      metabolic profiles (CMPs), to asymptomatic individuals. No national organizations
      currently recommend the complete CMP as a screening test for asymptomatic
      individuals in primary care settings. This study evaluated the value of CMPs in a
      health fair setting by measuring the ability of a health fair CMP to predict new
      medical diagnoses among residents of a sparsely populated rural county. METHODS:
      Volunteer participants submitted fasting blood samples at a health fair conducted
      by a county health center in a county with 2,531 total residents. CMP values were
      determined to be "normal" or "abnormal" based on laboratory reference ranges and
      clinical judgment of the health center physicians. Medical records were reviewed
      4 months later to determine if participants with abnormal CMP values had been
      diagnosed with new medical conditions as a result of the screening tests.
      Analysis was conducted to evaluate CMP test characteristics and determine whether
      demographic factors or specific CMP values predicted new medical diagnoses in the
      participants. RESULTS: Out of 478 health fair participants, 73 individuals had at
      least one abnormal CMP value. The most frequently occurring abnormal value was an
      elevated glucose level, with Hispanic participants significantly more likely to
      have this abnormality than whites. After all evaluation was completed, only about
      1% of tested subjects had a new diagnosis as a result of the screening CMP test;
      most abnormal CMP tests did not result in a new diagnosis. The positive
      predictive value for an abnormal test resulting in a new medical diagnosis was
      0.356. CONCLUSIONS: Comprehensive metabolic profiles have limited value as a
      screening tool in asymptomatic populations at health fairs.

PMID- 15243835
TI  - I am.

PMID- 15243841
TI  - Mammography screening in Switzerland: limited evidence from limited data.
AB  - QUESTIONS UNDER STUDY: In Switzerland controversy exists on how to summarise the
      evidence on the efficacy and effectiveness, as well as adverse effects, of
      mammography screening, and breast cancer mortality trends are often discussed in
      the context of the impact of mammography. PRINCIPLES/METHODS: Single-study
      publications, meta-analyses, and reports by international expert groups on
      mammography screening are reviewed. Breast cancer mortality trends from 1970-2000
      are reported and discussed in the context of the Swiss screening situation.
      RESULTS: In Switzerland breast cancer mortality rates for female Swiss nationals
      aged 50-79 years fell between 1990 and 2000 by some 25% in all language regions.
      The data from randomised studies in large populations in several countries with
      well organised mammography programmes prompt the conclusion that participation in
      organised screening programmes with rigorous quality standards reduces breast
      cancer mortality. The achievable long-term reduction in breast cancer mortality
      ranges from 5-20% in the target population provided that appropriate diagnostic
      investigation and treatment are available. To achieve this in Switzerland 830 to
      3300 women need to be invited to screening for ten years to prevent one death
      from breast cancer. The risk-benefit profile of mammography screening is likely
      to be less favourable if mammographies are performed outside the context of
      organised screening programmes. In Switzerland we are now confronted with growing
      regional disparities in access to screening mammography which is under systematic
      quality control. CONCLUSIONS: The decrease in breast cancer mortality in
      Switzerland is most probably due to treatment developments and changes in cause
      of-death coding. Public health measures in Switzerland should aim at regulating
      quality control for screening mammography, monitoring mammography use and
      improving the information on mammography available to women. For an evidence
      based decision regarding health insurance coverage of screening mammography in
      2007, large gaps need to be filled. The current coexistence of systematic
      screening programmes and opportunistic screening, with distinct regional
      differences, provides a unique opportunity for research into the merits and
      drawbacks of the two approaches.

PMID- 15243842
TI  - Patient use of the Internet for health care information in Switzerland.
AB  - STUDY AIMS: The aim of this study was to examine for the first time the frequency
      of Internet use for medical purposes by patients in Switzerland. METHODS: In 2001
      over a period of one month, 1604 patients at 8 medical practices in Switzerland
      completed a self-administered questionnaire on their access to the Internet and
      any search for medical information using this media. The attending physician
      supplied the patient's diagnosis and information on the severity of the disorder
      motivating the visit using a separate questionnaire. RESULTS: 46% of the patients
      included in the study had a personal computer, 33% had an Internet connection and
      10% used the Internet to find medical information. Age was inversely associated
      with the probability of having an Internet access, whereas educational level and
      command of the English language were factors directly associated with this. Among
      those patients with access to the Internet, young adults (25 to 44 years) and
      those with knowledge of the English language searched for medical information
      significantly more frequently. Furthermore, patients attending urban medical
      practices and those with a more severe level of disease more often sought health
      care information on the Internet. CONCLUSIONS: The proportion of patients in
      Switzerland who search for medical information on the Internet is similar to the
      rates observed in European English-speaking countries. The Internet allows
      patients to actively search for information concerning their own health problems
      but is not currently the most common source of information used by patients.
      Since health professionals generate, directly or indirectly, most of the medical
      information published on the Internet, additional research is needed to better
      understand patients' needs and expectations concerning medical information using
      this media.

PMID- 15243843
TI  - Current trends in illegal drug use and drug related health problems in
      Switzerland.
AB  - BACKGROUND AND METHOD: As part of the evaluation of the Confederation's measures
      to reduce drug related problems, a review of available data on drug use and drug
      related problems in Switzerland has been conducted. Source of data included:
      population surveys (adults and teenagers), surveys among drug users, health
      statistics (drug related and AIDS related deaths, HIV case reporting, drug
      treatments) police statistics (denunciations for consumption). RESULTS: The aims
      of reducing the number of dependent hard drug users have been achieved where
      heroin is concerned. In particular, there seems to have been a decrease in the
      number of people becoming addicted to this substance. For all other illegal
      substances, especially cannabis, the trend is towards an increased use, as in
      many European countries. As regards dependent drug users, especially injecting
      drug users, progress has been made in the area of harm reduction and treatment
      coverage. CONCLUSION: This epidemiological assessment can be used in the
      discussions currently engaged about the revision of the Law governing narcotics
      and will be a baseline for future follow up of the situation.

PMID- 15243844
TI  - Stage of change of cigarette smoking in drug dependent patients.
AB  - Nicotine cessation programmes in Switzerland, which are commonly based on the
      stage of change model of Prochaska and DiClemente (1983), are rarely offered to
      patients with illicit drug dependence. This stands in contrast to the high
      smoking rates and the heavy burden of tobacco-related problems in these patients.
      The stage of change was therefore assessed by self-administered questionnaire in
      100 inpatients attending an illegal drug withdrawal programme. Only 15% of the
      patients were in the contemplation or decision stage. 93% considered smoking
      cessation to be difficult or very difficult. These data show a discrepancy
      between the motivation to change illegal drug consumption habits and the
      motivation for smoking cessation. The high proportion of patients remaining in
      the precontemplation stage for smoking cessation, in spite of their motivation
      for illicit drug detoxification, may be due to the perception that cessation of
      smoking is more difficult than illicit drug abuse cessation.

PMID- 15243845
TI  - Vitamin C--a challenge in management of rabies.

PMID- 15243846
TI  - Swiss Medical Weekly Young Investigator's Award 2003: Clustering of
      cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null
      mice.

PMID- 15243847
TI  - Chronic fatigue syndrome (cfs).
AB  - The Chronic Fatigue Syndrome (CFS) is described based on the revision of Fukuda
      et al. The question "whether CFS can be discussed as a homogenous disorder?" has
      been reviewed and the answer is "no". Other overlapping syndromes are mentioned.
      Disorders with fatigue as a symptom are depression, somatisation, irritable bowel
      syndrome, effort-syndrome, hyperventilation, conservation-withdrawal. Among the
      pathogenetic factors of CFS immune systems disorders, neuroendocrine
      abnormalities, autonomic activity, neuroimaging, neuropsychological
      abnormalities, exercise capacity and muscle function and psychological processes
      (attribution, perception, symptom avoidance and neutralisation of conflicts) are
      discussed. Since CFS cannot be comprehended without knowledge of the ontogenetic
      development of the affect "fatigue", it is extensively described. Based on this
      knowledge, fatigue as an affect and the CFS are embedded in a context, which has
      as its basis the fight-flight reaction and the conservation-withdrawal reaction.
      Weighing the evidence, it is concluded that CFS in its varieties can best be
      understood as a manifestation of the activation of the two biological emergency
      reactions: fight-flight and conservation-withdrawal. The physician should
      interview and examine each individual patient according to the Harvey Cushing
      dictum: The physician should not only study the diseased organ, but the man with
      his diseased organ, and not only these. He should comprehend the man with his
      diseased organ in his environment. This leads to study of the biological,
      psychological and social factors contributing to each patient's illness. Work-up
      and therapy have to be based on this integrated approach. The latter encompasses
      conflict centred psychotherapy, stepwise increasing physical activation and
      antidepressive drugs.

PMID- 15243848
TI  - Cardiac resynchronization in severe heart failure and left bundle branch block: a
      single center experience.
AB  - OBJECTIVE: To assess the feasibility and longterm outcome of cardiac
      resynchronization therapy (CRT) in patients with impaired left ventricular
      function (LVEF <35%), left bundle branch block (QRS >120 ms) and dyspnoea NYHA 0
      III at a single centre. METHODS AND RESULTS: Forty-seven patients were referred
      for implantation of a CRT device. In only 4 patients (9%) the device could not be
      implanted due to technical problems during the procedure. In the remaining 43
      patients (65 +/- 10 years; 7 female) a CRT device was implanted. Follow-up time
      was 12 +/- 10 months. Twenty-one patients had dilated cardiomyopathy (DCM) and 22
      patients had coronary artery disease (CAD). NYHA functional class improved from
      3.0 +/- 1.4 to 2.5 +/- 0.7 (p <0.0001), accompanied by an improvement of LVEF
      [median 20% (range 15-25) vs 32% (range 20-40); p <0.0001]. A significant
      reduction of hospitalisation time for heart failure was found when the year
      before and the year after device implantation [18 days (range 5-27) vs 1 day
      (range 0-3); p <0.0001] were compared. Twelve (28%) patients, 9 with CAD, and 3
      with DCM died. Two CAD patients and all patients with DCM who died had a combined
      CRT device with implantable cardioverter/defibrillator. CONCLUSION: In patients
      with severely impaired LVEF and wide QRS due to LBBB, CRT is feasible and safe.
      It improved dyspnoea and LVEF and reduced hospitalisation stays for heart failure
      during long-term follow-up.

PMID- 15243849
TI  - Comparison of MRI graded cartilage and MRI based volume measurement in knee
      osteoarthritis.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between the
      femoral, tibial and patellar cartilage volume and MRI grading of the articular
      cartilage in patients with knee OA. METHODS: Articular cartilage volumes of 65
      postmenopausal women were determined by processing images acquired in the
      sagittal plane using a fast spin echo proton density-weighted sequence. The
      articular cartilages were divided into 5 compartments including lateral and
      medial tibial, lateral and medial femoral and patellar compartments. The
      articular cartilages were graded using a modified Outerbridge classification.
      Grade 0 indicated intact cartilage, grade 1 chondral softening with normal
      contour, grade 2 superficial fraying, grade 3 surface irregularity and thinning
      and grade 4 full thickness cartilage loss. The grades of articular cartilage were
      compared with cartilage volume measurements. RESULTS: In medial femoral
      cartilage, grade 1 had more volume compared to grade 0 cartilage (p: 0.017). In
      medial tibial cartilage, grade 1 had more volume compared to grade 0 and grade 2
      cartilage (p: 0.045 and p: 0.027, respectively). In patellar cartilage, grade 1
      cartilage had significantly more volume than grade 0 cartilage (p: 0.007). In
      lateral tibial and femoral cartilages, no significant difference was observed
      between grade 0 and grade 1 cartilage. CONCLUSIONS: Cartilage volume correlates
      well with MR grading of articular cartilage. The higher the grade of the
      cartilage the less the volume, with the exception of grade 1 lesions. Grade 1,
      reflects oedema in the cartilage and has a conflicting effect on volume
      measurement. The combination of MRI based volume measurement and grading of
      articular cartilage may provide an accurate method for the non-invasive
      evaluation and follow-up of articular cartilage.

PMID- 15243850
TI  - Left ventricular hypertrophy: diagnostics pitfalls.
AB  - Isolated left ventricular hypertrophy, in the absence of hypertension or aortic
      stenosis, is commonly attributed to hypertrophic cardiomyopathy (HCM). According
      to the clinical setting, however, other differential diagnoses should be
      considered. The diagnosis of cardiac amyloidosis may be very challenging
      especially when the clinician is confronted with various aspects typical of both
      pathologies. The work-up of this case shows how non-invasive cardiac
      investigations are sometimes not sufficiently conclusive for distinguishing
      between the two pathologies, and that only endomyocardial biopsy (EMB) can
      confirm cardiac involvement secondary to systemic amyloidosis. The prognostic and
      therapeutic differences between the two diseases, as well as the contextual
      aspects of the case in point--namely a case of multiorgan failure--serve as an
      example of how a definitive diagnosis can be attained by means of a
      multidisciplinary approach in order to reach a definitive treatment plan.

PMID- 15243851
TI  - Guidelines for the clinical management of atrial fibrillation: a practical
      perspective.
AB  - PURPOSE: Since the management of atrial fibrillation may be difficult in the
      individual patient, our purpose was to develop simple clinical recommendations to
      help the general internist manage this common clinical problem. DATA SOURCES:
      Systematic review of the literature with evaluation of data-related evidence and
      framing of graded recommendations. DATA SYNTHESIS: Atrial fibrillation affects
      some 1% of the population in Western countries and is linked to a significant
      increase in morbidity and mortality. The management of atrial fibrillation
      requires individualised evaluation of the risks and benefits of therapeutic
      modalities, relying whenever possible on simple and validated tools. The two main
      points requiring a decision in clinical management are 1) whether or not to
      implement thromboembolic prevention therapy, and 2) whether preference should be
      given to a "rate control" or "rhythm control" strategy. Thromboembolic
      prophylaxis should be prescribed after individualised risk assessment: for
      patients at risk, oral anticoagulation with warfarin decreases the rate of
      embolic complications by 60% and aspirin by 20%, at the expense of an increased
      incidence of haemorrhagic complications. "Rate control" and "rhythm control"
      strategies are probably equivalent, and the choice should also be made on an
      individualised basis. To assist the physician in making his choices for the care
      of an atrial fibrillation patient we propose specific tables and algorithms, with
      graded recommendations. CONCLUSIONS: On the evidence of data from the literature
      we propose simple algorithms and tables for the clinical management of atrial
      fibrillation in the individual patient.

PMID- 15243852
TI  - Affective distress and fibromyalgia.
AB  - PRINCIPLES: Elevated rates of lifetime and current psychiatric disorders,
      elevations of psychological self-report measures assessing depression, anxiety
      and hypochondriasis have been reported in fibromyalgia syndrome (FMS) patients as
      well as studies refuting these findings. Studies comparing FMS patients with
      rheumatoid arthritis (RA) patients provide discrepant data. The aim of this paper
      is to compare FMS patients with RA patients and healthy controls with respect to
      psychological measures in a case control design. METHODS: Fifty subjects with
      FMS, 20 with RA and 42 healthy controls were assessed with respect to anxiety,
      depression, pain intensity and disability. Three logistical regression models
      were performed to test whether higher levels of a psychological measure
      (disability, depression or anxiety) are associated with one disease rather than
      another, or with one disease rather than with healthy controls. For each
      regression model, the best exploratory covariates were determined using receiver
      operating characteristic (ROC) curves. RESULTS: In the logistic regression,
      anxiety scores were the most important covariate determining the likelihood of
      having FMS whereas depression scores increased the chances of being an RA
      patient. Age and disability scores did not differ between FMS and RA.
      CONCLUSIONS: Affective distress is not specific to FMS patients, but the manner
      in which affective distress is incorporated into the patient's life is worth
      studying. FMS.seems to be associated with anxiety rather than depression.

PMID- 15243853
TI  - Low power laser treatment in patients with knee osteoarthritis.
AB  - The aim of this study was to investigate the analgesic efficacy of low power
      laser therapy in patients with knee osteoarthritis (OA). The study design was
      randomised, placebo-controlled and single blinded. Sixty patients with knee OA
      according to the American College of Rheumatology criteria were included and
      randomly assigned to three treatment groups: active laser with dosage of 3 J/per
      painful point, active laser with a dosage of 1.5/J per painful point and placebo
      laser treatment groups. A Gal-Al-As diode laser device was used as a source of
      low power laser with a power output of 50 mW and a wavelength of 830 nm. The
      patients were treated 5 times weekly with 10 treatments in all. The clinical
      assessments included Western Ontario and McMaster Universities osteoarthritis
      index (WOMAC) pain, stiffness and physical function subscales. In addition, the
      intensity of pain at rest and on activation was evaluated on a visual analogue
      scale. Compared to baseline, at week 3 and at month 6, no significant improvement
      was observed within the groups. Similarly, no significant differences were found
      among the treatment groups at any time. With the chosen laser type and dose
      regimen the results that we obtained in this study, suggest that low-level laser
      therapy has no effect on pain in patients with knee OA.

PMID- 15243854
TI  - Preimplantation diagnosis in Switzerland--birth of a healthy child after polar
      body biopsy.
AB  - In Switzerland preimplantation genetic diagnosis is limited by law to polar body
      biopsy (PBB). The indications for PBB include unexplained recurrent miscarriage
      and improvement of the outcome of in vitro fertilisation (IVF) cycles in women at
      an advanced reproductive age. In this article we report the first birth of a
      healthy child after polar body biopsy in Switzerland in a case of unexplained
      miscarriage after IVF.

PMID- 15243855
TI  - American Society of Clinical Oncology--40th Annual Meeting. Monoclonal
      antibodies. 5-8 June 2004, New Orleans, LA, USA.

PMID- 15243856
TI  - American Society of Clinical Oncology--40th Annual Meeting. EGFR/VEGF. 5-8 June
      2004, New Orleans, LA, USA.

PMID- 15243857
TI  - American Society of Clinical Oncology--40th Annual Meeting. Selected highlights.
      5-8 June 2004, New Orleans, LA, USA.

PMID- 15243858
TI  - American Diabetes Association--64th Scientific Sessions. 4-8 June 2004, Orlando,
      FL, USA.

PMID- 15243859
TI  - American Diabetes Association--64th Scientific Sessions. Targeting amylin. 4-8
      June 2004, Orlando, FL, USA.

PMID- 15243860
TI  - American Diabetes Association--64th Scientific Sessions. Insulin. 4-8 June 2004,
      Orlando, FL, USA.

PMID- 15243861
TI  - BIO 2004 Annual International Convention. Part I. 6-9 June 2004, San Francisco,
      CA, USA.

PMID- 15243862
TI  - BIO 2004 Annual International Convention. Part II. 6-9 June 2004, San Francisco,
      CA, USA.

PMID- 15243863
TI  - American Urological Association Annual Meeting--AUA 2004. 8-13 May 2004, San
      Francisco, CA, USA.
AB  - Significant areas of new drug development discussed at this year's American
      Urological Association (AUA) meeting included: antioxidants, immunosuppressants,
      anti-androgens, kinase inhibitors, immunotherapeutic agents and antitumor
      vaccines. The poster and podium sessions devoted to urologic neoplasia
      concentrated on novel drug and vaccine development.

PMID- 15243864
TI  - Pharmaceutical Sciences World Congress--Second World Congress of the Board of
      Pharmaceutical Sciences of FIP. The global translation of science into drug
      development in advancing therapy. 29 May-3 June 2004, Kyoto, Japan.

PMID- 15243865
TI  - Therapeutic insight 2004. 3-4 May 2004, Jersey City, NJ, USA.

PMID- 15243866
TI  - Psychiatric Disorders--SMi conference. 24-25 May 2004, London, UK.

PMID- 15243867
TI  - The potential for BACE1 inhibitors in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a debilitating neurodegenerative disease of the
      elderly characterized by the loss of memory and other cognitive functions.
      Currently marketed drugs for the treatment of this disease only offer symptomatic
      relief, and, consequently, there is a large unmet clinical need for disease
      modifying therapies for the treatment of AD. Substantial research efforts are
      focused on inhibiting the proteases involved in the generation of the
      amyloidogenic beta-amyloid (A beta) peptide. One of these key proteases, beta
      secretase, was identified as a novel transmembrane aspartic protease and named
      BACE1. Due to its pivotal role in A beta production, many pharmaceutical
      companies are actively pursuing the challenging task of developing BACE1
      inhibitors for evaluation in the clinic.

PMID- 15243868
TI  - Leukotriene modifiers in asthma management.
AB  - The prevalence of asthma is increasing, especially among children. Despite the
      attention focused on the acute phase of asthma, asthmatic airways demonstrate
      increased inflammatory cell infiltration and irreversible structural alterations
      (remodeling). Thus, therapy must transcend the control of symptoms and focus on
      the prevention of chronic inflammation, which progressively evolves toward airway
      remodeling. Leukotrienes have been demonstrated to play a causative role both in
      the early bronchoconstriction noted in asthmatics and in the late chronic
      inflammatory component, and drugs that can inhibit the actions or synthesis of
      leukotrienes (leukotriene modifiers) are now available by prescription.

PMID- 15243869
TI  - Histamine-selective H3 receptor ligands and cognitive functions: an overview.
AB  - This review presents a link between histamine and cognition and provides an
      overview on the effect of histamine and selective ligands of histamine receptors
      on experimental models for learning, memory and cognitive functions, with a
      special focus on recently developed H(3) receptor ligands. Studies suggest a
      tremendous potential for H(3) antagonists in cognitive function disorders.

PMID- 15243870
TI  - Suberanilohydroxamic Acid. Aton Pharma.
AB  - Aton Pharma Inc, under license from the Memorial Sloan-Kettering Cancer Center,
      is developing suberanilohydroxamic acid (SAHA), a cytodifferentiating agent and
      histone deacetylase inhibitor, as a potential cancer chemopreventive.

PMID- 15243871
TI  - ["Aside yet right in the middle" -- the situation of siblings of mentally ill
      patients].

PMID- 15243872
TI  - [Homeless women with psychiatric disorders -- a field study].
AB  - AIM: The aim of the study was to investigate the psychosocial situation of all
      homeless women in a southern German university town. METHOD: The scope, structure
      and whereabouts of the target group were initially unknown. 17 of 22 homeless
      women identified agreed to participate in an extensive study including the
      Structured Clinical Interview for DSM-IV (SKID-I). RESULTS: The prevalence of
      diagnosed psychiatric disorders was 71 %; the leading disorder was substance
      abuse/dependence (43 %), followed by anxiety disorders (35 %) and schizophrenia
      (12 %). Multiple diagnoses were made in 35 % of the women. DISCUSSION: Striking
      features were the often early onset of homelessness and the reticence in seeking
      help. The flight from violence was a crucial precipitant of the loss of the home
      and should also be discussed in the context of the development of the psychiatric
      disorders. This study is the first involving women outside major cities.
      Precipitant situation, need for help and help-seeking pattern appear to deviate
      markedly from those of homeless men. The results should be verified in further
      gender-specific studies.

PMID- 15243873
TI  - [Psychiatric morbidity in homeless single men].
AB  - AIM: The aim of this cross sectional study was to establish the extent of
      psychiatric morbidity among homeless men and compare this group with a sample of
      formerly homeless. METHOD: [corrected] 82 homeless and a comparison group of 37
      formerly homeless were interviewed using a psychopathological interview according
      to AMDP (Arbeitsgemeinschaft fur medizinische Dokumentation) as well as selected
      modules of the CIDI (Composite International Diagnostic Interview). Diagnoses
      were established according to ICD-10. RESULTS: The lifetime prevalence of
      psychiatric disorders was 95.1 %, the current prevalence was 87.8 %. Substance
      related disorders were the most common group of disorders. In the formerly
      homeless prevalences were slightly lower. CONCLUSIONS: Psychiatric morbidity
      among the homeless is high. Services have to be tailored to meet the needs of
      this special group. Formerly homeless continue to need intensive psychiatric
      input.

PMID- 15243874
TI  - [Frequent use of psychiatric inpatient services analysed from three different
      perspectives].
AB  - OBJECTIVE: Frequent utilization of psychiatric inpatient care was mainly analysed
      by quantitative methods. The present study combines quantitative with qualitative
      methods and discusses the results obtained from these different perspectives.
      METHOD: The quantitative analysis is based on data from 184 schizophrenia
      patients, who were observed over a period of 2(1/2) years. Twenty of the
      identified frequent users and 6 employees of psychiatric facilities were
      interviewed by means of qualitative methods as to the causes of frequent use of
      inpatient care. RESULTS: Predictors of frequent use identified in the
      quantitative study were found again in the qualitative analysis. Opportunities
      for alternative care for frequent users suggested by the staff of psychiatric
      facilities include social treatment in the community, day structuring activities
      and sheltered work. Patients consider work, compliance securing and better
      contact with office based psychiatrists to be important factors. CONCLUSIONS:
      Patients and staff give different priorities to their suggestions for
      interventions, but are, in most cases, of the opinion, that part of hospital
      admissions of frequent users could be avoidable by means of alternative services.

PMID- 15243875
TI  - [Bodyweight in inpatients with schizophrenia].
AB  - OBJECTIVE: Epidemiological studies show overweight to be a major health problem
      in Germany. There is some evidence that psychiatric patients often are
      overweight. In view of the high frequency of weight gain during the treatment
      with neuroleptics, particularly atypicals, in this study the bodyweight of
      schizophrenics should be examined. METHODS: The body-mass-index (BMI) of two
      samples of schizophrenic inpatients was compared to BMI-data of the German
      general population. RESULTS: 90 inpatients with the first episode of
      schizophrenic psychoses showed an average BMI of 22.2 +/- 3.3. The BMI in all age
      groups were lower compared to the general population, but in a follow-up these
      patients showed a higher weight gain. 238 chronic schizophrenic inpatients with
      at least 5 years duration of illness (mean 15.3 +/- 8.3 years) showed BMI-values
      in the range of the general population. Only the age group 30 - 35 years showed a
      significantly higher BMI. However, in many age groups of schizophrenic inpatients
      the proportion of obesity (BMI > 30) was higher compared to the general
      population. CONCLUSIONS: The bodyweight of first episode schizophrenics is lower
      compared to the general population. In contrast, chronic schizophrenic patients
      frequently are overweight or show obesity. However, thus far the causes of
      pronounced weight gain in schizophrenic patients remain to be elucidated.

PMID- 15243876
TI  - [A psychodynamic approach in counselling vulnerable persons for Chorea Huntington
      -- a case report].
AB  - The availability of predictive testing for neurodegenerative diseases such as
      Chorea Huntington has far-reaching consequences on psychological, ethical, and
      legal issues. The special situation of persons vulnerable for the disease
      requires a comprehensive counselling including psychotherapeutic measures. On the
      basis of a case report, the authors outline a psychodynamic practice, which
      intends not only the identification of deliberate arguments and development of
      coping strategies, but also a clarification of unconscious backgrounds and
      expectations. In the discussion, the necessity of sufficient time is stressed
      that allows the reflection of repressed motives in respect of the genetic
      testing.

PMID- 15243877
TI  - [Ziprasidone-augmentation of clozapine].
AB  - OBJECTIVES: In cases of treatment-resistant schizophrenic psychoses combined
      application of atypical antipsychotic drugs is an often-used strategy. METHOD: We
      report the case of a 35-year old man with paranoid schizophrenia, whose symptoms
      turned out to be resistant to the application of olanzapine, risperidone and
      quetiapine. After switch to clozapine paranoid delusions remitted, but
      schizophrenic negative symptoms persisted and side effects limited the patient's
      compliance. Augmentation with ziprasidone allowed a reduction of the clozapine
      dose and ameliorated the affective deficits. RESULTS: Positive and negative
      symptoms were well controlled. In spite of a transient hyperprolactinaemia and
      sexual dysfunction the patient was highly content. DISCUSSION: The combined
      application of ziprasidone and clozapine follows a neurobiological rationale,
      seems able to reduce side effects, and should be further evaluated with respect
      to risk and benefit in prospective studies.

PMID- 15243878
TI  - Comparison of various submucosal injection solutions for maintaining mucosal
      elevation during endoscopic mucosal resection.
AB  - BACKGROUND AND STUDY AIMS: One of the major complications of endoscopic mucosal
      resection (EMR) for gastrointestinal tumors is perforation, and the most
      effective way of preventing perforation is to elevate the lesion sufficiently by
      endoscopic injection of fluid into the submucosa. MATERIALS AND METHODS: In order
      to compare the lesion-lifting properties of several different solutions, 1 ml of
      each of the following solutions was injected into the submucosa of the resected
      porcine stomach: normal saline, 3.75 % NaCl, 20 % dextrose water, 10 % glycerin
      with 0.9 % NaCl plus 5 % fructose, and two sodium hyaluronate (SH) solutions.
      RESULTS: Significantly higher initial elevation was produced by both SH
      solutions, and it remained higher than that achieved by the other solutions at
      all times. Hypertonic solutions, especially 10 % glycerin with 0.9 % NaCl plus 5
      % fructose, tended to produce and maintain greater mucosal elevation than normal
      saline, but the difference was not significant. CONCLUSIONS: SH solutions were
      the most suitable ones for producing and maintaining long-term mucosal elevation,
      while the superiority of hypertonic solutions over normal saline was not clearly
      demonstrated.

PMID- 15243880
TI  - Magnifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using
      an endocytoscopy system.
AB  - BACKGROUND AND STUDY AIMS: The aim of the present study was to observe the
      endoscopic characteristics of cells on the surface layer of superficial
      esophageal carcinomas in vivo using an endocytoscopy system and to compare the
      findings with those in normal squamous epithelium. PATIENTS AND METHODS:
      Superficial esophageal cancers in 12 patients were examined with methylene blue
      staining using an endocytoscopy system. RESULTS: The endocytoscopy system and
      methylene blue staining made it possible to observe cells on the surface of the
      squamous epithelium in normal esophageal mucosa. Normal cells were arranged
      homogeneously, and the nucleus cytoplasm ratio was uniform and low. In esophageal
      cancers, the density of cells was found to be much greater than that in normal
      squamous epithelium. The cell distribution was also irregular and the cells were
      extremely heterogeneous, with the nuclei having different staining, size, and
      shape characteristics. The nucleus cytoplasm ratio was also very irregular.
      CONCLUSIONS: Examining esophageal tissue using the endocytoscopy system described
      here makes it possible to observe detailed histological alterations in esophageal
      lesions in vivo.

PMID- 15243879
TI  - Different mixtures of sodium hyaluronate and their ability to create submucosal
      fluid cushions for endoscopic mucosal resection.
AB  - BACKGROUND AND STUDY AIMS: Sodium hyaluronate (SH) is a promising submucosal
      injection solution during endoscopic mucosal resection, but its high cost is an
      obstacle to more widespread use. The aim of this study was to identify an
      appropriate low-cost SH solution by varying the molecular weight of SH and mixing
      various solutions with it. MATERIALS AND METHODS: The viscoelasticity of various
      SH solutions was first measured. The concentrations of two 1 % SH preparations
      with different molecular weights (800 kDa and 1900 kDa) were adjusted to 0.5 %,
      0.25 %, and 0.125 %, using 0.9 %/3.75 % normal saline (NS), 5 %/20 % dextrose
      water (DW), and a glycerin solution (Glyceol): 10 % glycerin with 0.9 % normal
      saline plus 5 % fructose. The ability of these SH solutions to create submucosal
      fluid cushions (SFCs) was then investigated in the stomachs of two live minipigs.
      RESULTS: The 0.25 % 1900 kDa SH/NS solution and the 0.125 % 1900 kDa SH/20 % DW
      solution created a similar viscoelasticity to that of the 0.5 % 800 kDa SH/NS
      solution. The ability of these solutions to create SFCs was also similar. In
      addition, the 0.125 % 1900 kDa SH/Glyceol solution created similar SFCs, with a
      synergistic effect of increased viscoelasticity and the hypertonic nature of
      glycerin. CONCLUSIONS: A mixture of higher molecular weight sodium hyaluronate
      with a sugar solution (particularly 20 % dextrose), with or without glycerin,
      should be regarded as a cost-effective option for creating SFCs instead of the
      conventional SH solution made with the same amount of a 1 % 800 kDa SH
      preparation and normal saline.

PMID- 15243881
TI  - Factors influencing clinical applications of endoscopic balloon dilation for
      benign esophageal strictures.
AB  - BACKGROUND AND STUDY AIMS: The purpose of this study was to investigate the
      safety and clinical effectiveness of a controlled radial expansion (CRE) balloon
      catheter in dilating benign esophageal strictures, and to assess factors
      influencing the effectiveness of this procedure. PATIENTS AND METHODS: From
      February 2000 to June 2002, 25 patients with documented benign esophageal
      strictures at our hospital were enrolled and treated with CRE balloon dilation.
      There were 17 men and eight women, with ages ranging from 30 to 82 years. The
      average age of the enrolled patients was 56.1 years. All of the strictures were
      dilated using CRE dilators under direct visualization, without fluoroscopic
      monitoring. The dilation diameters were planned in series up to 15 mm using a
      "rule of three". If dysphagia and esophageal strictures recurred during the
      clinical follow-up after completion of a series of dilations, additional dilation
      was carried out until symptomatic relief was achieved. Effective treatment was
      defined as the ability of patients with or without repeated dilations to maintain
      a solid or semisolid diet for more than 12 months. Depending on the effectiveness
      and duration of treatment, the patients were divided into three groups: group A,
      the successful group in which the initial series of dilations was effective
      without the need for any additional dilation for recurrent strictures or
      dysphagia; group B, the relapse group, in which the initial series of dilations
      was effective, but additional dilations were needed due to recurrent strictures
      or dysphagia; and group C, the group in which the initial series of dilations
      failed or consecutive dilations could not be carried out due to intolerance.
      RESULTS: The 25 patients received a total of 95 sessions of dilation (3.8 +/- 1.2
      sessions per patient). There were 11 patients in group A, 11 patients in group B,
      and three patients in group C. The median follow-up period was 16.5 months (range
      12 - 32 months). The number of initial dilations required to achieve symptomatic
      relief showed a negative correlation with the pre-dilation diameter of the
      strictures ( r = - 0.92, P < 0.01). Thinner strictures required more dilations
      before symptomatic relief was achieved. In addition, the stricture length in
      group B (5.4 +/- 3.4 cm) was significantly longer than that in group A (2.6 +/-
      1.1 cm) ( P = 0.009). The overall success rate was 88 % (22 of 25), including 100
      % in the 21 patients with a stricture length of less than 8 cm and 25 % in the
      four patients with a stricture length more than 8 cm ( P = 0.02). CONCLUSIONS:
      CRE balloon dilation without fluoroscopy is an effective treatment for esophageal
      strictures less than 8 cm in length. Pre-dilation diameter and stricture length
      are factors that influence the numbers of dilations required and the need for
      additional dilations.

PMID- 15243882
TI  - Computerized diagnosis of Helicobacter pylori infection and associated gastric
      inflammation from endoscopic images by refined feature selection using a neural
      network.
AB  - BACKGROUND AND STUDY AIM: We investigated whether analysis of endoscopic images
      using a refined feature selection with neural network (RFSNN) technique could
      predict Helicobacter pylori-related gastric histological features. PATIENTS AND
      METHODS: A total of 104 dyspeptic patients were prospectively enrolled for
      panendoscopy and gastric biopsy for histological evaluation using the updated
      Sydney system. The endoscopic images of each patient were analyzed to obtain 84
      image parameters. The significant image parameters from 30 randomly selected
      patients (15 with and 15 without H. pylori infection) associated with
      histological features were used to develop the RFSNN model. This was then used to
      test the sensitivity and specificity of the image parameters obtained from the
      remaining 74 patients for the prediction of the presence of H. pylori infection
      and related histological features. RESULTS: The RFSNN technique had a sensitivity
      of 85.4 % and a specificity of 90.9 % for the detection of H. pylori infection.
      Moreover, RFSNN was highly accurate (> 80 %) in predicting the presence of
      gastric atrophy, intestinal metaplasia and the severity of H. pylori-related
      gastric inflammation. CONCLUSIONS: RFSNN is an effective computerized technique
      for assessing the presence of H. pylori infection and related gastric
      inflammation and precancerous lesions. By using RFSNN to analyze endoscopic
      images, a comprehensive evaluation of the stomach may be done, thus avoiding the
      need for invasive but localized biopsy sampling for histological examination.

PMID- 15243883
TI  - Colon preparation for magnification endoscopy: a rapid novel approach.
AB  - BACKGROUND AND STUDY AIMS: Minute lesions in the colon are of increasing clinical
      interest. Conventional endoscopic techniques are inadequate for visualizing these
      lesions, and magnification chromoendoscopy is required to identify them. This
      study compared the effectiveness of a simpler colon preparation method with the
      standard technique. Patients and Methods : Seven patients received dilute
      methylene blue (0.05 %) by enema prior to the endoscopic evaluation. The extent,
      quality, and ease of dye delivery were compared with the standard methods.
      RESULTS: Dye delivery by enema extended to the splenic flexure and was uniformly
      applied, and advancement of the endoscope was easier. This alternative method was
      better tolerated by patients (visual analogue scale 1.9 +/- 0.3 vs. 3.8 +/- 0.8;
      P = 0.004). CONCLUSION: This rapid and reliable method of visualizing the entire
      left colon with dye magnification allows magnification chromoendoscopy to be
      carried out in a convenient manner that is also less painful for the patient.

PMID- 15243884
TI  - Endoscopic biopsies from normal-appearing terminal ileum and cecum in patients
      with suspected colonic tuberculosis.
AB  - BACKGROUND AND STUDY AIMS: Colonic tuberculosis is generally diagnosed by
      colonoscopy and targeted biopsy of lesions. However, the diagnostic yield of
      colonic biopsies is not very good. So far as we are aware, there have been no
      studies investigating the role of biopsies from endoscopically normal-appearing
      cecum and terminal ileum in diagnosing colonic or ileal tuberculosis, or both.
      PATIENTS AND METHODS: Patients with a clinical suspicion of colonic tuberculosis,
      in whom no endoscopic abnormalities were found on colonoscopy or ileoscopy, were
      included in the study. Multiple biopsies were obtained from the cecum and ileum.
      RESULTS: Fifty patients were studied. Intubation of the terminal ileum was
      possible in 43 patients (86 %). Histological examination of biopsies obtained
      from the cecum and terminal ileum showed noncaseating granuloma in two patients.
      Both of these biopsies were from the terminal ileum. In two other patients,
      collections of loosely arranged epithelioid cells were observed. This established
      the diagnosis in these four patients (8 %). In the remaining 46 patients,
      histology showed nonspecific inflammation in 18 patients (in the cecum in 15 and
      in the terminal ileum in seven). The other biopsies did not show any
      abnormalities (33 from the cecum, 34 from the terminal ileum). CONCLUSIONS:
      Histological examination of biopsies from the normal-appearing cecum and terminal
      ileum is useful in a small but significant number of patients with colonic
      tuberculosis.

PMID- 15243885
TI  - Endosonography versus helical computed tomography for locoregional staging of
      gastric cancer.
AB  - BACKGROUND AND STUDY AIMS: Endosonography (EUS) has been shown to be more
      accurate than incremental computed tomography (CT) in the local (T) and regional
      (N) staging of gastric carcinoma; however, EUS has never been compared with
      helical CT (HCT). The fifth edition of the TNM classification changed the
      guidelines for N-staging of gastric carcinoma. The accuracy of imaging methods in
      this new system remains unknown. PATIENTS AND METHODS: Staging accuracy of EUS
      and HCT were compared prospectively with pathological or intraoperative findings
      in 88 gastric carcinoma patients. Staging was done according to the fourth and
      fifth editions of the TNM classification. EUS was done with a radial echo
      endoscope, and HCT with a scanner with two rows of detectors (two-phase contrast
      enhanced scanning of a water-filled stomach). RESULTS: The T-staging accuracy of
      EUS (63 %, CI 52 - 73 %) was superior to the accuracy of HCT (44 %, CI 34 - 55 %;
      P = 0.021). N-staging accuracy of both methods was similar when the fourth
      edition of the TNM classification was used (EUS 47 %, CI 34 - 60 %; HCT 52 %, CI
      38 - 65 %). However, HCT was more accurate than EUS when the fifth edition of the
      classification was applied (EUS 30 %, CI 18 - 43 %, HCT 47 %, CI 34 - 60 %; P =
      0.044). The accuracy of detection of lymph node metastases was similar for both
      methods (EUS 67 %, CI 54 - 78 %; HCT 77 %, CI 64 - 86 %). CONCLUSIONS: EUS is
      more accurate than HCT in the T-staging of gastric carcinoma. Both methods are
      comparable for N-staging, when this is done according to the older, fourth
      edition of the TNM classification. If the fifth edition is used, EUS is less
      accurate than HCT.

PMID- 15243886
TI  - Endoscopic ultrasonography in the diagnosis and staging of neoplasms of the head
      and neck.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine-needle aspiration
      (EUS-FNA) is a minimally invasive and highly accurate method of detecting
      mediastinal lymph-node metastases in gastrointestinal and lung cancer. Little
      information is available regarding the use of EUS-FNA to stage tumors in the head
      and neck region. This study reports experience with EUS in the diagnosis and
      staging of these tumors and their mediastinal spread. PATIENTS AND METHODS: The
      records of patients who underwent EUS for diagnosis and/or staging of head and
      neck tumors were reviewed. Referral criteria were suspected invasion of the
      esophagus by a lower-neck mass on cervical computed tomography (CT) or magnetic
      resonance imaging (MRI), or mediastinal lymphadenopathy > 10 mm on a chest CT.
      RESULTS: Thirty-two patients (23 men, nine women; mean age 65 years, range 44 -
      80) were referred and underwent 35 EUS examinations. In one patient, EUS was not
      possible due to a benign esophageal stricture. In 17 patients with suspected
      esophageal invasion on CT scans, EUS demonstrated invasion of the esophagus in
      four cases and of the pleura in one; 12 tumors showed no visible invasion of
      adjacent structures. The other 17 examinations were carried out for suspected
      mediastinal metastatic disease. In eight cases, EUS-FNA confirmed metastatic
      disease, whereas only benign changes were shown in the other nine cases. EUS-FNA
      also provided the first tissue diagnosis in two primary tumors and identified
      malignancy in one patient with no CT suspicion of positive mediastinal lymph
      nodes. EUS avoided the need for more invasive investigations in all patients with
      mediastinal lymphadenopathy, and it changed the management in 12 of the 17
      patients (71 %) with suspected esophageal invasion and in eight of the 17
      patients (47 %) with suspected mediastinal disease. CONCLUSIONS: EUS with FNA
      provides a viable approach to the diagnosis and staging of tumors in the head and
      neck region when there is a suggestion of esophageal invasion on CT or MRI, or
      enlarged mediastinal lymph nodes. EUS with FNA may avoid the need for
      mediastinoscopy or other more invasive techniques for staging of these neoplasms.

PMID- 15243887
TI  - Influence of endoscopic papillary balloon dilation and endoscopic sphincterotomy
      on sphincter of oddi function: a randomized controlled trial.
AB  - BACKGROUND AND STUDY AIM: Endoscopic papillary balloon dilation (EPBD) is assumed
      to have a theoretical advantage over endoscopic sphincterotomy (EST) in
      preserving sphincter of Oddi function because it does not involve cutting the
      biliary sphincter. Although attempts have been made to study the influence of
      EPBD and EST on sphincter of Oddi function, there is little agreement on this
      issue. In this study we used a method different from those described in previous
      reports to clarify whether EPBD or EST preserves sphincter of Oddi function
      better. PATIENTS AND METHODS: 200 patients with bile duct stones who met the
      eligibility criteria were randomly assigned to EPBD (n = 104) or an EST (n = 96)
      group. Sphincter of Oddi function was estimated by measurement of the activity of
      pancreatic enzymes in the common bile duct (CBD). Pure bile was collected
      immediately before EPBD or EST, at 1 week and at 1 year after the procedure. We
      also statistically investigated 14 factors other than EPBD or EST that might have
      the potential to affect sphincter of Oddi function. RESULTS: There was no
      significant difference between the baseline characteristics of the EPBD and EST
      groups. A total of 91 patients (46 in the EPBD group and 45 in the EST group)
      remained in the trial. Pure bile was collected from the CBD of 86 patients (43
      EPBD and 43 EST) 1 week after the procedure. CBD stones were extracted
      successfully in all cases. Before the procedure, there were no significant
      differences in the levels of the five pancreatic enzymes between the EPBD and EST
      groups. At 1 week after the procedure, in both groups, there were significant
      increases in the levels of the five pancreatic enzymes. At 1 year after the
      procedure a complete series of pancreatic enzyme analyses was done in 33 patients
      (12 EPBD and 21 EST). There was no significant difference between the levels of
      the five pancreatic enzymes immediately before and 1 year after EPBD and EST.
      When the pancreatic enzyme levels of the two groups were directly compared, there
      was no significant difference at 1 year after the procedure, but the EPBD group
      had significantly higher levels at 1 week following the procedure. CONCLUSION: In
      this study it was found that in patients with CBD stones both EPBD and EST
      preserve sphincter of Oddi function.

PMID- 15243888
TI  - Ode to the submucosal fluid cushion.

PMID- 15243889
TI  - Endoscopic diagnosis and treatment of watermelon stomach.

PMID- 15243890
TI  - On writing: write the abstract, and a manuscript will emerge from it!

PMID- 15243891
TI  - Local endoscopic removal of duodenal carcinoid tumors.
AB  - A swift and aggressive diagnostic and therapeutic approach is advisable when
      managing submucosal or polypoid lesions in the duodenum, since it is not possible
      to distinguish small, benign, and unremarkable duodenal growths macroscopically
      from malignant tumors such as carcinoids. This paper presents a systematic review
      of the published literature listed in Medline, focusing on the results after
      endoscopic treatment of duodenal carcinoids during the last 15 years; on the
      biological behavior of duodenal carcinoids; and on the endoscopic appearance of
      duodenal carcinoids. Endoscopic ultrasonography (EUS) is extremely useful in the
      diagnostic and preoperative work-up. The results indicate that endoscopic removal
      of duodenal carcinoids smaller than 1 cm that are located outside the
      periampullary region, with no EUS signs of invasion of the muscularis propria, is
      a safe, patient-friendly, adequate, and effective treatment.

PMID- 15243892
TI  - European Society of Gastrointestinal Endoscopy guideline for video capsule
      endoscopy.

PMID- 15243893
TI  - Refractory Whipple's disease with anaemia: first lessons from capsule endoscopy.
AB  - Whipple's disease is a chronic multisystem disorder caused by infection with the
      rod-shaped bacterium, Tropheryma whippelii. We report the case of a 65-year-old
      woman with intestinal Whipple's disease that had been refractory to monotherapy
      with a number of antibiotics over a 2-year period. The patient then presented
      with watery diarrhoea, cachexia (body mass index 18 kg/m (2)) and chronic anaemia
      (haemoglobin 7.6 g/dl). Wireless capsule endoscopy showed that the disease
      affected the entire small intestine. Focal occult areas of bleeding were observed
      in different parts of the jejunum. The capsule's transit time through the small
      intestine was 2 hours 43 minutes. Capsule endoscopy allows novel insights into
      the pathophysiology of Whipple's disease.

PMID- 15243894
TI  - Esophageal perforation as a complication of EndoCinch endoluminal
      gastroplication.
AB  - Endoscopic gastroplasty is being promoted as a new minimally invasive procedure
      for the treatment of gastroesophageal reflux disease. In the case presented here,
      however, we encountered abdominal perforation as a severe complication of this
      procedure. Because immediate action was taken when the symptoms developed, and by
      maintaining close collaboration with the surgeons, it was possible to keep the
      treatment minimally invasive: the leakage was detected endoscopically and the
      defect was closed laparoscopically and covered by a fundoplication. This
      experience emphasises the importance of appropriate management of complications
      as part of the evaluation of new endoscopic methods.

PMID- 15243895
TI  - Cap-assisted endoscopic retrograde cholangiopancreatography in a patient with a
      Billroth II gastrectomy.

PMID- 15243896
TI  - A new device for endoscopic mucosal resection.

PMID- 15243897
TI  - Incorrect macroscopic diagnosis of colonic carcinoma made at endoscopy.

PMID- 15243898
TI  - Endoscopic papillary balloon dilation in the management of common bile duct
      stones in patients with Roux-En-Y reconstruction.

PMID- 15243899
TI  - Methylene blue dye injection: an adjuvant technique in the management of buried
      bumper syndrome?

PMID- 15243900
TI  - Primary natural killer-cell lymphoma of the gastrointestinal tract.

PMID- 15243901
TI  - [Evidence-based prevention of cholecystolithiasis].
AB  - Evidence based prevention of cholecystolithiasis. Cholesterol cholelithiasis is
      one of the most common and expensive gastroenterological diseases. Beside common
      exogenous risk factors, recent molecular genetic studies have identified genetic
      risk factors for both cholesterol and pigment stone formation. Examples are low
      phospholipid-associated cholelithiasis due to mutations of the gene encoding the
      hepatocanalicular phosphatidylcholine transporter, and pigment stones in
      association with mutations of the ileal bile salt transporter gene. Evidence
      based options for primary prevention of cholecystolithiasis include physical
      activity, slow weight reduction, regular vitamin C supplementation, and moderate
      coffee consumption. The ongoing genome projects provide the basis for future
      epidemiological studies of human gallstone (LITH) genes, which might offer new
      prospects for individual risk assessment and prevention of gallstones.

PMID- 15243902
TI  - [High prevalence of osteoporosis in adult cystic fibrosis patients].
AB  - BACKGROUND AND OBJECTIVE: In adult patients with cystic fibrosis bone metabolism
      may be altered by multiple mechanisms, such as abnormal calcium homeostasis,
      malnutrition, chronic inflammation or inactivity in the course of respiratory
      failure. In contrast to the high prevalence of osteoporosis in CF patients before
      lung transplantation, data from different CF collectives show great variation. It
      was the purpose of our cross-sectional study to determine changes in bone
      metabolism by measuring bone mineral density, and assessing calcium metabolism
      and clinical characteristics in adult patients (mean age 32 years) with cystic
      fibrosis. PATIENTS AND METHODS: Bone mineral density (quantitative digital
      radiography), parameters of calcium homeostasis and clinical characteristics were
      determined in 34 adult patients with cystic fibrosis. RESULTS: The mean age of
      the study population was 32 years (range 20 to 47; 21m: 13f). 13 patients had
      normal T-values (mean bone mineral density in young adults), whereas 11 patients
      (32 %) had osteopenia and 10 (29 %) had osteoporosis. Calcium homeostasis was
      abnormal in only one case. In contrast T-values were positively correlated with a
      low body mass index (p = 0.01) and a low one-second forced expiratory volume
      (FEV1) (p < 0.05). CONCLUSION: Decreased mineral bone density is a frequent
      complication in adult patients with cystic fibrosis, but does not occur
      inevitably even in long-standing disease (up to 47 years). In our cohort
      measurable alterations of calcium homeostasis could be avoided by consistent
      substitution policy. The main determinants of a low T-value were poor nutritional
      status, lowered serum calcium or phosphate concentrations and severely impaired
      lung function as indicator of the progression of the disease. Screening of adult
      patients with CF can be recommended especially in presence of malnutrition or
      poor lung function.

PMID- 15243903
TI  - [Ethical decision-making at the end of life--knowledge and attitudes of medical
      students].
AB  - BACKGROUND AND OBJECTIVE: Physicians are often confronted with ethical and legal
      questions at the end of life. In this study we asked medical students at the
      universities of Mainz and Berlin (Charite) about the "Guidelines on Physicians'
      Aid to the Dying" issued by the German Medical Association: their moral attitude
      and legal knowledge regarding the limitation of medical procedures at the end of
      life and their judgement about the quality of medical education on these topics.
      METHODS: 569 medical students in their 1. and 4. clinical semester as well as the
      final year of their studies in Mainz and students in their 5. year of studies in
      Berlin received a questionnaire containing 14 items relating to ethical and legal
      questions at the end of life. RESULTS: 308 (54.1%) completed the questionnaire.
      7.8% knew the contents of the "Guidelines on Physicians' Aid to the Dying".
      Between 10% (use of catecholamines) and 62% (parenteral feeding) viewed
      withholding or withdrawing life-sustaining measures from dying patients as
      illegal. 39-72% held the view that measures of nutrition and hydration were part
      of the indispensable basic medical care for every patient. 12-26% were unsure
      with respect to their moral views about withholding and withdrawal of therapy.
      82% felt insufficiently prepared for dealing with ethical questions at the end of
      life. CONCLUSION: Only a minority of medical students was informed about ethical
      principles and legal regulations regarding end-of-life decisions. Teaching of
      ethical and legal knowledge and integration of these issues into clinical problem
      solving should be mandatory.

PMID- 15243904
TI  - [Chronic upper abdominal pain without improvement after using proton pump
      inhibitors].
AB  - HISTORY AND CLINICAL FINDINGS: A 57-year-old woman was admitted to our hospital
      because of relapsing, therapy-resistant pain, predominantly in the upper abdomen.
      The symptoms began 6 years previously, after a resection of parts of the small
      intestine for an ileus of unclear cause. Subsequently 11 (!) gastroscopies showed
      repeatedly gastritis and Helicobacter pylori- negative gastric and/or small
      intestinal ulcers which were treated with proton pump inhibitors. This led to no
      significant improvement of the complaints and produced no healing. DIAGNOSTIC
      FINDINGS AND THERAPY: Gastroscopy showed, at the transition of the gastric fundus
      to the corpus, an area with multiple, fibrin coated ulcers. Histologically an
      active, chronic gastric ulcer was seen, with perifocally dense inflammatory
      infiltration by predominantly eosinophils. In the colon these histological
      findings, although clearly less pronouncedly, were also seen i.e. an eosinophilic
      gastroenteropathy. This was initially treated with 60 mg/day prednisone. Under
      this treatment she became completely symptom-free. After a dose reduction to 5 mg
      prednisone daily the symptoms occurred again. Thereupon long-term
      immunosuppressive therapy with 100 mg azathioprine daily was introduced. Regular
      clinical and endoscopic monitoring showed a complete remission of the ulcers and
      no complaints after 1.5 years. CONCLUSION: Our case report shows that in patients
      with uncharacteristic abdominal pain and gastric ulcers, which improve
      inadequately under the usual medication such as proton pump inhibitors, less
      common illnesses must be considered. Despite the rarity of eosinophilic
      gastroenteropathy the exact (histological) diagnosis plays an important role,
      because a specific therapy with corticosteroids and/or azathioprine can induce
      improvement of the symptoms.

PMID- 15243905
TI  - [Hypothyroidism--case report].

PMID- 15243906
TI  - [Hypothyroidism--diagnosis].

PMID- 15243907
TI  - [Hypothyroidism--therapy].

PMID- 15243910
TI  - [Acquired von Willebrand syndrome].

PMID- 15243911
TI  - [What should one pay attention to during surgery shortly after brachytherapy with
      coated stents?].

PMID- 15243912
TI  - [Simulation of a colon carcinoma: diuretic-induced ulcerative, stenosing ischemic
      colitis].

PMID- 15243913
TI  - Resistance to helminth infection: the case for interleukin-5-dependent
      mechanisms.

PMID- 15243914
TI  - Immune responses in human necatoriasis: association between interleukin-5
      responses and resistance to reinfection.
AB  - Cytokine and proliferative responses to Necator americanus infection were
      measured in a treatment-reinfection study of infected subjects from an area of
      Papua New Guinea where N. americanus is highly endemic. Before treatment, most
      subjects produced detectable interleukin (IL)-4 (97%), IL-5 (86%), and interferon
      (IFN)- gamma (64%) in response to adult N. americanus antigen. Pretreatment IFN-
      gamma responses were negatively associated with hookworm burden, decreasing by 18
      pg/mL for each increase of 1000 eggs/gram (epg) (n=75; P<.01). Mean IFN- gamma
      responses increased significantly after anthelmintic treatment, from 166 to 322
      pg/mL (n=42; P<.01). The intensity of reinfection was significantly negatively
      correlated with pretreatment IL-5 responses, decreasing by 551 epg for each 100
      pg/mL increase in production of IL-5 (n=51; P<.01). These data indicate that
      there is a mixed cytokine response in necatoriasis, with worm burden-associated
      suppression of IFN- gamma responses to adult N. americanus antigen. Resistance to
      reinfection is associated with the parasite-specific IL-5 response.

PMID- 15243916
TI  - Identification of genomic responses to collagen binding by trophozoites of
      Entamoeba histolytica.
AB  - Attachment of Entamoeba histolytica trophozoites to collagen is a known stimulus
      for parasite activation, leading to subsequent tissue destruction and invasion.
      To identify cellular mechanisms of trophozoite activation, we assessed global
      variations in gene expression during collagen interaction with E. histolytica. A
      shotgun DNA microarray was constructed by use of 9600 random inserts from an E.
      histolytica genomic DNA library. Through differential hybridization, key
      differences between gene expression in collagen-activated trophozoites and that
      in nonactivated trophozoites were identified. Fourteen differentially regulated
      clones were reproducibly identified and selected for sequencing. Among the genes
      identified were those coding for (1) components of a signaling cascade that had
      been previously hypothesized to transmit responses to cell attachment, (2)
      adapter proteins for vesicle formation, and (3) proteins that are implicated in
      cytoskeletal reorganization and locomotion. Two known virulence-factor genes-
      those for cysteine proteinases and amebapore--also were up-regulated in response
      to collagen stimulation. These results provide important new clues about how a
      pathogen orchestrates responses to the host environment as well as a new tool for
      the analysis of other aspects of Entamoeba species infection and pathogenicity.

PMID- 15243915
TI  - Iron deficiency and malaria among children living on the coast of Kenya.
AB  - Both iron deficiency and malaria are common in much of sub-Saharan Africa, and
      the interaction between these conditions is complex. To investigate the
      association between nutritional iron status, immunoglobulins, and clinical
      Plasmodium falciparum malaria, we determined the incidence of malaria in a cohort
      of children between the ages of 8 months and 8 years who were living on the
      Kenyan coast. Biochemical iron status and malaria-specific immune responses were
      determined during 2 cross-sectional surveys. We found that the incidence of
      clinical malaria was significantly lower among iron-deficient children (incidence
      rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.51-0.99; P<.05), that the
      incidence of malaria was significantly associated with plasma ferritin
      concentration (IRR for log ferritin concentration, 1.48; 95% CI, 1.01-2.17;
      P<.05), and that iron status was strongly associated with a range of malaria
      specific immunoglobulins. We conclude that iron deficiency was associated with
      protection from mild clinical malaria in our cohort of children in coastal Kenya
      and discuss possible mechanisms for this protection.

PMID- 15243917
TI  - A population-based study of vaginal human papillomavirus infection in
      hysterectomized women.
AB  - We compared point prevalences and determinants of human papillomavirus (HPV) DNA
      detection by testing enrollment vaginal specimens from hysterectomized women
      (n=569) and enrollment cervical specimens from nonhysterectomized women (n=6098)
      >or=30 years old, using MY09/MY11 L1 consensus-primer polymerase chain reaction.
      The subjects were participating in a population-based cohort study (n=10,049) in
      Guanacaste, Costa Rica, that was initiated in 1993. Non-cancer-associated HPV
      types, especially types 61, 71, and 72, were detected more frequently in the
      vaginal specimens from hysterectomized women (23.7% [95% confidence interval
      [CI], 20.3%-27.4%]) than in the cervical specimens from nonhysterectomized women
      (16.7% [95% CI, 15.7%-17.6%]) (P=.0001). There was no difference between the
      prevalences of cancer-associated HPV types in hysterectomized women and those in
      nonhysterectomized women; in both groups, the prevalence of HPV DNA was greater
      in women with multiple lifetime sex partners. We infer from our data that the
      cervical transformation zone may not be needed for cancer-associated HPV
      infection but may be uniquely susceptible to HPV-induced carcinogenesis; we also
      infer that specific phylogenetic groups of HPV (i.e., A3/A4/A15) may have a
      predilection for vaginal epithelium.

PMID- 15243918
TI  - Prevalence and determinants of genital infection with papillomavirus, in female
      and male university students in Busan, South Korea.
AB  - BACKGROUND: Little is known about the prevalence of human papillomavirus (HPV)
      infection in young adults in Asia. METHODS: We invited female and male students
      in Busan, South Korea, to participate in a survey that included, for females,
      self-collection of vaginal cells and, for males, physician-performed collection
      of exfoliated genital cells. The prevalences of 25 HPV types were evaluated, by a
      polymerase chain reaction-based assay, in 672 female students (median age, 19
      years) and in 381 male students (median age, 22 years). RESULTS: HPV DNA was
      detected more frequently in female students (15.2%) than in male students (8.7%);
      in both sexes, high-risk HPV types were predominant. Among sexually active
      students, HPV prevalence was 38.8% in females and 10.6% in males. In female
      students, currently smoking cigarettes and having multiple lifetime sex partners
      were the strongest risk factors for HPV infection; in male students, associations
      between HPV prevalence and sexual habits were similar to those in female students
      but never attained statistical significance. CONCLUSIONS: Young women in South
      Korea start having penetrative sexual intercourse relatively late (median age, 18
      years), but, once they begin, HPV prevalence quickly rises to levels comparable
      with those found in university students in the United States and in northern
      Europe. The high rate of participation in our study suggests that trials of new
      vaccines against HPV may be feasible among university students in South Korea.

PMID- 15243919
TI  - An elementary school outbreak of varicella attributed to vaccine failure: policy
      implications.
AB  - BACKGROUND: Since licensure in the United States, studies have shown that
      varicella vaccine's overall effectiveness ranges from 44% to 100%, with
      substantial protection against moderate and severe varicella; however,
      breakthrough illness has been documented in up to 56% of vaccinated individuals.
      METHODS: A varicella outbreak occurred in a Minnesota school with 319 students.
      Phone surveys were conducted with students' parents. Information was collected on
      students who had recent varicella infections, including onset date, rash
      characteristics, duration, and underlying medical conditions. RESULTS: Fifty-four
      cases occurred after a primary breakthrough case. Twenty-nine (53%) students had
      been vaccinated. Unvaccinated students had an increased risk of moderate
      varicella, compared with vaccinated students (relative risk [RR], 4.4 [95%
      confidence interval [CI], 2.2-9.1]; P<.001). The vaccine was 56% effective at
      preventing any varicella and 90% effective against moderate illness. Students
      vaccinated >or=5 years before the outbreak had a greater risk of breakthrough
      varicella than did those vaccinated within <or=4 years (RR, 2.6 [95% CI, 1.3
      5.4]; P<.01). CONCLUSIONS: Vaccinated students presented with milder varicella
      symptoms than did unvaccinated students. Individuals with breakthrough illness
      can be highly infectious. Time since varicella vaccination was associated with
      illness. Despite 29 breakthrough cases, the varicella vaccine conferred a high
      degree of protection against moderate illness.

PMID- 15243920
TI  - Shedding of human herpesvirus 8 in oral and genital secretions from HIV-1
      seropositive and -seronegative Kenyan women.
AB  - Polymerase chain reaction was used to determine the prevalence and correlates of
      human herpesvirus 8 (HHV8) in saliva, mouth, cervical, vaginal, plasma, and
      peripheral-blood mononuclear cell (PBMC) samples from 174 HHV8-seropositive
      female prostitutes in Mombasa, Kenya. The prevalence of detection of HHV8 was 32%
      in saliva samples, 28% in mouth swabs, 4% in cervical swabs, 2.3% in vaginal
      swabs, 9% in plasma samples, and 18% in PBMC samples. Human immunodeficiency
      virus type 1 (HIV-1) seropositivity was associated with detection of HHV8 from
      any mucosal surface (odds ratio, 2.1 [95% confidence interval, 1.1-4.0]). In HIV
      1-seropositive women, there was no association between detection of HHV8 and
      either CD4 count or HIV-1 viral load.

PMID- 15243921
TI  - Isopentenyl pyrophosphate-reactive Vgamma9Vdelta 2 T helper 1-like cells are the
      major gammadelta T cell subset recovered from lesions of patients with genital
      herpes.
AB  - Herpes simplex virus (HSV)-specific T cells are essential to control and resolve
      genital herpes (GH). To investigate the potential involvement of gamma delta T
      cells in GH, T cells were recovered and expanded, by mitogenic stimulation, to T
      cell lines from the genital lesions of 17 patients with GH and 5 control subjects
      who had other diseases. Relatively high numbers of gamma delta T cells-
      predominantly, V gamma 9V delta 2 T cells--were detected only in the T cell lines
      of the patients with GH. Intralesional V gamma 9V delta 2 T cell clones did not
      recognize HSV-infected cells, but they showed reactivity to isopentenyl
      pyrophosphate and Daudi cells. The T cell clones secreted interferon- gamma,
      tumor necrosis factor- alpha, interleukin (IL)-8, macrophage inflammatory protein
      1 alpha, and RANTES (regulated on activation, normally T cell expressed or
      secreted), but they secreted no or limited IL-4. The results of the present study
      suggest the infiltration and putative involvement of isopentenyl pyrophosphate
      reactive V gamma 9V delta 2 T helper 1-like cells in individuals with GH.

PMID- 15243922
TI  - Evaluation of systemic inflammatory responses in neonates with herpes simplex
      virus infection.
AB  - Neonatal herpes simplex virus (HSV) infection is a severe disease with high
      mortality and morbidity. To investigate the pathogenesis of neonatal HSV
      infection, we examined inflammatory responses and markers of apoptosis in
      patients with neonatal HSV infection. Concentrations of inflammatory cytokines
      and markers of apoptosis were significantly higher in patients with disseminated
      HSV infection and were correlated with HSV load. It appears that the
      immunopathological damage that results from host responses to viral infection
      leads to organ dysfunction in patients with neonatal HSV infection.

PMID- 15243923
TI  - Oral activity of ether lipid ester prodrugs of cidofovir against experimental
      human cytomegalovirus infection.
AB  - Infection with human cytomegalovirus (HCMV) can cause serious complications in
      bone-marrow and solid-organ transplant recipients, and current therapies are not
      optimal. We evaluated 2 orally active ether lipid ester analogues of cidofovir
      (CDV)--hexadecyloxypropyl-CDV (HDP-CDV) and octadecyloxyethyl-CVD (ODE-CDV)--in
      severe combined immunodeficient mice in which either human fetal retinal tissue
      or human fetal thymus and liver tissue had been implanted and was later infected
      with HCMV. Our results indicate that orally administered treatment with either
      HDP-CDV or ODE-CDV is 4-8-fold more active, on a molar basis, than is
      intraperitoneally administered CDV. These data suggest that HDP-CDV and ODE-CDV
      should be further evaluated as potential antiviral agents for treatment of HCMV
      infection.

PMID- 15243924
TI  - Higher human T lymphotropic virus (HTLV) provirus load is associated with HTLV-I
      versus HTLV-II, with HTLV-II subtype A versus B, and with male sex and a history
      of blood transfusion.
AB  - BACKGROUND: High human T lymphotropic virus (HTLV)-I provirus load (VL) has been
      associated with an increased risk of HTLV-associated myelopathy, but little is
      known about variation in HTLV-I or -II VLs by demographic characteristics and
      risk behaviors. METHODS: We measured HTLV-I and HTLV-II VLs in a large cohort of
      127 HTLV-I-seropositive and 328 HTLV-II-seropositive former blood donors, by use
      of real-time polymerase chain reaction using tax primers. Multivariable linear
      regression was used to control for confounding by relevant covariates. RESULTS:
      The mean VLs were 3.28 log(10) copies/10(6) peripheral blood mononuclear cells
      (PBMCs) (range, 0.5-5.3 log(10) copies/10(6) PBMCs) for HTLV-I and 2.60 log(10)
      copies/10(6) PBMCs (range, 0.05-5.95 log(10) copies/10(6) PBMCs) for HTLV-II
      (P<.0001). HTLV-II VLs were higher in those subjects with subtype A infection
      (mean, 2.82 log(10) copies/10(6) PBMCs) than in those with subtype B infection
      (mean, 2.29 log(10) copies/10(6) PBMCs) (P=.005). Higher HTLV-I VL was associated
      with previous receipt of a blood transfusion (P=.04), and lower HTLV-II VL was
      associated with female sex (P=.007). These associations persisted in virus
      specific multivariate linear regression models controlling for potential
      confounding variables. CONCLUSIONS: VL was significantly higher in HTLV-I than in
      HTLV-II infection and was higher in HTLV-II subtype A than in HTLV-II subtype B
      infection. Chronic HTLV VLs may be related to the infectious dose acquired at the
      time of infection, with higher VLs following acquisition by blood transfusion and
      lower VLs following sexual acquisition.

PMID- 15243925
TI  - Complexity and diversity of hepatitis C virus RNA in african americans and
      whites: analysis of the envelope-coding domain.
AB  - African Americans infected with hepatitis C virus (HCV) are less responsive than
      whites to interferon-based therapy. HCV quasi species have been implicated. Quasi
      species complexity and diversity were evaluated in matched African American and
      white individuals. Complexity and diversity in the first hypervariable region
      were similar in the 2 groups. Both the frequency of nonsynonymous amino acid
      substitutions and the mean ratio of nonsynonymous mutations to synonymous
      mutations were greater in clones derived from white patients. Racial differences
      in amino acid usage at otherwise conserved positions were observed. Differences
      in amino acid representation at key positions are suggestive of immunologic and
      functional selection along racial lines.

PMID- 15243926
TI  - Association of human-leukocyte-antigen class I (B*0703) and class II (DRB1*0301)
      genotypes with susceptibility and resistance to the development of severe acute
      respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is a public health concern worldwide. By
      studying the human leukocyte antigen (HLA) types A, B, DR, and DQ alleles in 90
      Chinese patients with serologically confirmed SARS infections, we identified a
      strong association between HLA-B*0703 (OR, 4.08; 95% CI, 2.03-8.18; P=.00072
      [Bonferroni-corrected P value, P(c) <.0022]) and -DRB1*0301 (OR, 0.06; 95%, 0.01
      0.47; P=.00008 [after Bonferroni correction, P<.0042]) and the development of
      SARS. Moreover, the frequency of B*0703 and B60 coinheritance (9.6%; 95% CI, 4.6%
      19.0%) in our SARS group was significantly higher (P=3x10(-9)) than that expected
      in the general population (0.4%). These genetic data will critically affect both
      the study of the pathogenesis of SARS and the design of vaccination programs.

PMID- 15243927
TI  - Effect of antiviral treatment on the outcome of secondary bacterial pneumonia
      after influenza.
AB  - Secondary bacterial pneumonia is an important cause of influenza-associated
      death. Although antibacterial therapy is standard, antiviral therapy has been
      ignored because viral infections usually resolve by the time bacterial pneumonia
      presents. In the present study, antiviral compounds were tested in a mouse model
      of secondary pneumococcal pneumonia after influenza. Treatment with oseltamivir
      improved survival in mice from 0% to 75%, even when therapy was delayed for up to
      5 days after infection with influenza virus. In mice, treatment with rimantadine
      had no effect on survival. Treatment with ampicillin cleared infection but, in
      the absence of treatment with oseltamivir, did not improve survival. Pneumonia
      developed in only 7 of the 22 mice receiving oseltamivir, and subsequent
      treatment with ampicillin resulted in cure (100% survival). Treatment of the
      predisposing influenza-virus infection with inhibitors specific for the viral
      neuraminidase may improve the efficacy of antibiotics and increase survival in
      persons who are at high risk for complications and mortality during influenza.

PMID- 15243928
TI  - Diagnostic and prognostic implications of endotoxemia in critical illness:
      results of the MEDIC study.
AB  - A novel assay for endotoxin, based on the ability of antigen-antibody complexes
      to prime neutrophils for an augmented respiratory burst response, was studied in
      a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the
      day of ICU admission, 57.2% of patients had either intermediate (>or=0.40
      endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative
      infection was present in 1.4% of patients with low EA levels, 4.9% with
      intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and
      a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of
      severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and
      16.8% for patients with low, intermediate, and high EA levels, respectively.
      Stepwise logistic regression analysis showed that elevated Acute Physiology and
      Chronic Health Evaluation II score, gram-negative infection, and emergency
      admission status were independent predictors of EA.

PMID- 15243929
TI  - Immune responses and antibody decay after immunization of adolescents and adults
      with an acellular pertussis vaccine: the APERT Study.
AB  - As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5
      serum samples were obtained, over an 18-month period, from 101 ACP-vaccine
      recipients and 99 control subjects, to assess ACP antibody response and decay.
      Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous
      hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by
      enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of
      the subjects, 16%-19% had preimmunization values of antibodies to PT that were
      above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the
      subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were
      above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3
      ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent
      decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%,
      respectively; the IgG antibody response and decay suggests that geometric mean
      titers likely remain above the LOQ for 2-9 years and above the threshold of
      detection for 4-13 years. These findings support the use of ACP booster
      immunizations for adolescents and adults, to provide sustained levels of
      antibody.

PMID- 15243930
TI  - Concentration of antipneumococcal antibodies as a serological correlate of
      protection: an application to acute otitis media.
AB  - BACKGROUND: For the licensing of new pneumococcal vaccines, it is vital to be
      able to predict their protective efficacy on the basis of immunogenicity.
      However, the serological correlates of protection have not been established for
      pneumococcal diseases. METHODS: A total of 1666 children were immunized with the
      pneumococcal conjugate vaccine. Acute otitis media (AOM) events were identified,
      and middle-ear fluid was cultured for pneumococci. The association between the
      concentration of antibodies against serotypes 6B, 19F, and 23F and the risk of
      AOM caused by the homologous serotypes or by the cross-reactive serotype 6A was
      assessed. An association model was used to predict efficacy at different
      geometric mean concentrations (GMCs). RESULTS: An association between antibody
      concentration and risk of AOM was found, but with large differences between
      serotypes. On the basis of the association, the predicted efficacy for 19F was
      negligible up to the highest GMC tested. In contrast, 6B was found to be highly
      efficacious (>65%) at a GMC of 0.5 microg/mL. CONCLUSIONS: The results challenge
      the view that a new vaccine candidate should always induce antibody
      concentrations that are not inferior to those produced by the licensed vaccine.
      Furthermore, the differences between serotypes caution against defining a common
      correlate of protection that is applicable to all serotypes.

PMID- 15243931
TI  - Immunogenicity of pneumococcal vaccination of patients with cochlear implants.
AB  - BACKGROUND: Pneumococcal meningitis is a rare but potentially fatal complication
      of cochlear implantation. METHODS: A prospective study was conducted of the
      immunogenicity of pneumococcal vaccination in 174 patients with cochlear implants
      (CIs). The cohort was divided into groups of patients with impaired hearing due
      to meningitis (P(1)), cranial malformations (P(2)), or an unknown cause (P(3))
      and was stratified by age as follows: <2 years (A(1)), 2-5 years (A(2)), and >5
      years (A(3)). We determined immunoglobulin (Ig) levels for IgG subclasses 1-4 and
      serum concentrations of antibodies against pneumococci before and 4-6 weeks after
      vaccination. Group A(1) received the 7-valent pneumococcal conjugate vaccine (PCV
      7), group A(2) received PCV-7 or the 23-valent pneumococcal polysaccharide
      vaccine (PPV-23), and group A(3) received PPV-23. RESULTS: IgG, IgM, and IgG1
      levels were significantly lower in group P(1), compared with the other patient
      groups and with historic data for healthy control subjects, suggesting a
      decreased antibody response. Group P(1) had lower levels of pneumococcal
      antibodies, compared with groups P(2) and P(3) before vaccination (P<.05,
      pneumococcal serotypes 4 and 9V). Irrespective of the underlying condition, all
      patients showed a sufficient antibody response after 1 dose of vaccine. In
      children 2-5 years of age, PCV-7 was significantly more immunogenic than PPV-23.
      CONCLUSIONS: PCV-7 should be administered to all CI recipients younger than 6
      years and older than 6 years who are at an increased risk for bacterial
      meningitis. CI recipients with a history of bacterial meningitis should undergo
      immunological evaluation.

PMID- 15243932
TI  - Use of type V group B streptococcal conjugate vaccine in adults 65-85 years old.
AB  - One-third of the cases of invasive group B streptococcal (GBS) disease now occur
      in adults >or=65 years old. Serotype V is most frequent among these invasive
      isolates. The safety and immunogenicity of type V GBS capsular polysaccharide
      (CPS)-tetanus toxoid (V-TT) conjugate vaccine (CV) were assessed in 32 healthy
      adults 65-85 years old who were randomized to receive a single intramuscular dose
      of V-TT CV (n=22) or licensed tetanus-diphtheria toxoid vaccine (Td) (n=10;
      double-masked design). V-TT CV elicited significant increases in type V CPS
      specific immunoglobulin (Ig) G, IgM, and IgA serum concentrations 4, 8, 26, and
      52 weeks after immunization. V-TT-induced type V CPS-specific antibodies promoted
      the opsonophagocytic killing of type V GBS in vitro. Both vaccines elicited
      similar concentrations of TT-specific IgG in 4-week postimmunization serum
      samples. These results suggest the potential for prevention of invasive type V
      GBS infections in healthy elderly adults through immunization.

PMID- 15243933
TI  - Immune responses to an oral typhoid vaccine strain that is modified to
      constitutively express Vi capsular polysaccharide.
AB  - Protection against typhoid fever might be best achieved by a vaccine that
      stimulates IgG antibody to Vi capsular polysaccharide (Vi) in serum, IgG antibody
      to O antigen in serum, and cell-mediated immune responses. Live typhoid vaccines
      have not elicited anti-Vi antibody, presumably because Vi expression is highly
      regulated. CVD 909 is an oral attenuated typhoid vaccine candidate that is
      engineered to constitutively express Vi. In the present study, CVD 909, at doses
      of 10(6-9) cfu, was orally administered to 32 healthy adults, and immune
      responses were measured. Although many of the volunteers generated antibody
      secreting cell responses to Vi, only 2 of the 32 volunteers generated anti-Vi IgG
      antibody in serum.

PMID- 15243934
TI  - Inhibition of complement activation by a secreted Staphylococcus aureus protein.
AB  - Staphylococcus aureus can cause a variety of acute and chronic diseases. The
      ability of S. aureus to cause persistent infections has been linked to its
      ability to evade or inactivate host immune responses. We have identified a
      secreted 19-kDa protein produced by S. aureus that binds to the complement
      protein C3. N-terminal sequencing of this protein identified it as the
      extracellular fibrinogen-binding protein (Efb). In this study, we demonstrate
      that Efb can bind to the alpha -chain of C3 and inhibit both the classical and
      alternative pathways of complement activation. In addition, we show that Efb can
      inhibit complement-mediated opsonophagocytosis in a dose-dependent manner and
      that Efb inhibits complement activity by blocking deposition of C3 or by
      preventing further complement activation beyond C3b. These data suggest that Efb
      is a virulence factor involved in facilitating persistent S. aureus infections by
      interfering with complement activity in vivo.

PMID- 15243935
TI  - Association of IL12RB1 polymorphisms with pulmonary tuberculosis in adults in
      Morocco.
AB  - Five disease-causing genes, including the IL12RB1 gene that encodes the beta 1
      chain of the receptor for interleukin (IL)-12 (IL-12R beta 1), are known to be
      associated with the syndrome of Mendelian susceptibility to mycobacterial
      diseases. Some IL-12R beta 1-deficient patients present with tuberculosis as the
      only clinical phenotype. A comprehensive genetic study of IL12RB1 was conducted
      among 101 Moroccan families, including 157 offspring (age, >15 years) who had
      culture-positive pulmonary tuberculosis (PTB). The promoter, exons, and flanking
      intron regions of IL12RB1 in 40 randomly selected patients with PTB were entirely
      sequenced, leading to the detection of 19 variants (including 10 novel
      mutations). Blood cells obtained from individuals who were homozygous for any of
      the 13 most common variants responded to IL-12, indicating that these
      polymorphisms were not loss-of-function mutations. By use of a family-based
      study, 2 promoter polymorphisms that were in strong linkage disequilibrium were
      found to be associated with PTB, especially -2C-->T (odds ratio for CT or TT vs.
      CC, 2.69 [95% confidence interval, 1.19-6.09]). This result suggests that IL12RB1
      polymorphisms might influence the risk of development of PTB in adults.

PMID- 15243936
TI  - Immune response to postprimary tuberculosis in mice: Mycobacterium tuberculosis
      and Miycobacterium bovis bacille Calmette-Guerin induce equal protection.
AB  - We addressed the question of whether protective immunity induced by natural
      infection with Mycobacterium tuberculosis and that induced by vaccination with
      Mycobacterium bovis bacille Calmette-Guerin (BCG) differ in the murine model. We
      infected mice with M. tuberculosis Erdman, cured them by chemotherapy, and
      subsequently reinfected them with a low dose of M. tuberculosis H37Rv. The course
      of tuberculosis was compared with that in mice previously vaccinated with BCG
      Danish 1331. Protection against postprimary M. tuberculosis infection did not
      differ significantly between the 2 groups. After challenge infection, numbers of
      interferon- gamma -positive splenocytes did not differ between mice with primary
      infection and vaccinated mice. Splenocytes from primary M. tuberculosis-infected
      mice conferred marginally higher protection than did those from BCG-vaccinated
      mice. Serum transfer did not protect against reinfection in either group. Our
      data emphasize that natural infection with M. tuberculosis and vaccination with
      BCG do not differ in their capacity to induce protective immunity against
      tuberculosis and support the notions that reinfection contributes to the
      development of active disease and that any novel vaccine against tuberculosis has
      to perform better than both vaccination with BCG and immunity evoked by natural
      infection.

PMID- 15243938
TI  - Tissue-associated cytokine expression in HIV-positive persons with oropharyngeal
      candidiasis.
AB  - Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common
      infection in human immunodeficiency virus (HIV)-positive persons. Although CD4(+)
      T cells are considered to be important for host defense against C. albicans at
      the oral mucosa, a recent immunohistochemical evaluation of T cells in OPC
      lesions of HIV-positive persons with reduced CD4(+) T cells showed high numbers
      of CD8(+) T cells. The present study investigated tissue-associated expression of
      cytokine and chemokine mRNA at the site of infection. Results showed some effects
      of HIV (primarily increased chemokine mRNA levels) but little effect of blood
      CD4(+) T cells. In contrast, mRNA for several proinflammatory, T helper, and
      CD8(+) T cell-associated cytokines and chemokines were increased in subjects with
      OPC versus those without. These results support the presence of CD8(+) T cells in
      OPC lesions and suggest evidence for a response against OPC, despite reduced
      levels of CD4(+) T cells.

PMID- 15243937
TI  - HIV RNA testing in the context of nonoccupational postexposure prophylaxis.
AB  - BACKGROUND: The specificity and positive predictive value of human
      immunodeficiency virus (HIV) RNA assays have not been evaluated in the setting of
      postexposure prophylaxis (PEP). METHODS: Plasma from subjects enrolled in a
      nonoccupational PEP study was tested with 2 branched-chain DNA (bDNA) assays, 2
      polymerase chain reaction (PCR) assays, and a transcription-mediated
      amplification (TMA) assay. Assay specificity and positive predictive value were
      determined for subjects who remained negative for HIV antibody for >or=3 months.
      RESULTS: In 329 subjects examined, the lowest specificities (90.1%-93.7%) were
      seen for bDNA testing performed in real time. The highest specificities were seen
      with batched bDNA version 3.0 (99.1%), standard PCR (99.4%), ultrasensitive PCR
      (100%), and TMA (99.6%) testing. Only the 2 assays with the highest specificities
      had positive predictive values >40%. For the bDNA assays, increasing the cutoff
      point at which a test is called positive (e.g., from 50 copies/mL to 500
      copies/mL for version 3.0) increased both specificity and positive predictive
      values to 100%. CONCLUSIONS: The positive predictive value of HIV RNA assays in
      individuals presenting for PEP is unacceptably low for bDNA-based testing and
      possibly acceptable for PCR- and TMA-based testing. Routine use of HIV RNA assays
      in such individuals is not recommended.

PMID- 15243939
TI  - Impairment of the Schistosoma mansoni-specific immune responses elicited by
      treatment with praziquantel in Ugandans with HIV-1 coinfection.
AB  - We show that Ugandan adults coinfected with Schistosoma mansoni and human
      immunodeficiency virus type 1 (HIV-1) are able to mount S. mansoni-specific
      immune responses but that few such responses increase after treatment with
      praziquantel (PZQ). Levels of soluble worm antigen (SWA)-specific immunoglobulin
      (Ig) G1, IgG2, IgG3, IgG4, interleukin (IL)-4, and IL-5 increased significantly
      in HIV-negative participants after treatment with PZQ, whereas most soluble egg
      antigen-specific antibody responses and levels of interferon- gamma were
      unaltered. Only levels of SWA-specific IL-5 increased in HIV-1-coinfected
      participants after treatment. These deficiencies in immune responses may account
      for the previously reported increased susceptibility to infection and reinfection
      with S. mansoni in individuals coinfected with HIV-1.

PMID- 15243940
TI  - HIV type 1 and cytomegalovirus coinfection in the female genital tract.
AB  - The relationship between human immunodeficiency virus (HIV) type 1 and human
      cytomegalovirus (CMV) was studied in blood, saliva, and cervicovaginal lavage
      (CVL) specimens from 33 HIV-1-infected women. An association between HIV-1 RNA
      and CMV DNA was found in the CVL specimens, which also were tested for cytokine
      levels. Women with detectable CMV DNA in CVL specimens were more likely to have
      higher interleukin (IL)-1 beta and IL-8 levels than were women with undetectable
      CMV DNA in CVL specimens. More than 1 strain of CMV was detected in specimens
      from 2 patients. These results suggest mechanisms by which CMV coinfection could
      affect HIV-1 disease progression.

PMID- 15243941
TI  - Requirement of interleukin-17A for systemic anti-Candida albicans host defense in
      mice.
AB  - T cells are required for normal host defense against fungal infection, and
      individuals with T cell-deficiency syndromes are highly susceptible to fungal
      pathogens. Interleukin (IL)-17A is a proinflammatory cytokine that interconnects
      myeloid and lymphoid host defense. The role of murine (m) IL-17A/mIL-17A receptor
      (R) interactions was evaluated in a murine model of systemic candidiasis. In
      response to systemic challenge with Candida albicans, expression of mIL-17A was
      induced, and IL-17AR knockout (IL-17AR(-/-)) mice had dose-dependent,
      substantially reduced survival. Fungal burden in the kidneys of IL-17AR(-/-) mice
      was dramatically increased (25-fold at 96 h). In IL-17AR(-/-) mice, both
      mobilization of peripheral neutrophils and their influx to infected organs were
      significantly impaired and delayed. In vivo expression of mIL-17A protected
      normal mice from a lethal dose of C. albicans (100% at day 7 and 65% at day 42).
      The data suggest that the mIL-17A/mIL-17AR system is required for normal fungal
      host defense in vivo. IL-17A could have potential as a therapeutic cytokine for
      systemic C. albicans infections in immunocompromised patients with cancer or
      advanced acquired immunodeficiency syndrome.

PMID- 15243942
TI  - Role of mannose-binding lectin in the innate defense against Candida albicans:
      enhancement of complement activation, but lack of opsonic function, in
      phagocytosis by human dendritic cells.
AB  - Mannose-binding lectin (MBL) is a serum collectin believed to be of importance in
      innate immunity. We have investigated the role of MBL in the first-line defense
      against Candida albicans, an opportunistic fungal pathogen. MBL bound C. albicans
      via its lectin domain, resulting in agglutination of the organisms upon their
      outgrowth of hyphae. In a human in vitro MBL system, deposition of C4 fragments
      on C. albicans was increased when exogenous MBL was added to serum samples from
      MBL-deficient individuals. Similar enhancement of deposition of iC3b also was
      observed. MBL and enhanced opsonic C3 fragments mediated by MBL did not
      facilitate opsonophagocytosis of the organisms by monocyte-derived dendritic
      cells (DCs). However, MBL was found to inhibit the growth of C. albicans
      independently of complement activation, although, with complement activation,
      further inhibition was observed. We concluded that MBL plays an important role in
      the first-line defense against C. albicans without the need for
      opsonophagocytosis by DCs, in which a direct interaction of MBL with C. albicans
      results in agglutination and accelerated complement activation via the lectin
      pathway, leading to inhibition of growth.

PMID- 15243943
TI  - Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of
      invasive aspergillosis: variables that affect performance.
AB  - Invasive aspergillosis (IA) is a frequent complication of blood or marrow
      transplantation. Previous studies have reported that the Aspergillus
      galactomannan enzyme immunoassay (GM EIA) may be a useful diagnostic tool for IA,
      but its sensitivity is variable. We examined the performance of the GM EIA in 986
      serum samples from 67 patients. Results demonstrated that decreasing the index
      cutoff for positivity to 0.5 increased its sensitivity, with minimal loss of
      specificity. The low cutoff increased the duration of test positivity before
      diagnosis by clinical means. Sensitivity was highest in patients who did not
      receive preventative mold-active antifungals (87.5%). A rabbit model demonstrated
      that the level of circulating antigen correlated with the tissue fungus burden. A
      quantifiable response to antifungal therapy in clinical samples and the rabbit
      model supports the development of this assay for early diagnosis and therapeutic
      monitoring. The 0.5 cutoff may allow for better performance as an early
      diagnostic test.

PMID- 15243944
TI  - Transmission of isoniazid-resistant tuberculosis.

PMID- 15243946
TI  - Seronegative hepatitis C virus infection, not just RNA detection.

PMID- 15243947
TI  - COMMENTARY: Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC. Oral
      transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman
      primates. J Infect Dis 1980; 142:205-208.

PMID- 15243948
TI  - Clustering-neural network models for freeway work zone capacity estimation.
AB  - Two neural network models, called clustering-RBFNN and clustering-BPNN models,
      are created for estimating the work zone capacity in a freeway work zone as a
      function of seventeen different factors through judicious integration of the
      subtractive clustering approach with the radial basis function (RBF) and the
      backpropagation (BP) neural network models. The clustering-RBFNN model has the
      attractive characteristics of training stability, accuracy, and quick
      convergence. The results of validation indicate that the work zone capacity can
      be estimated by clustering-neural network models in general with an error of less
      than 10%, even with limited data available to train the models. The clustering
      RBFNN model is used to study several main factors affecting work zone capacity.
      The results of such parametric studies can assist work zone engineers and highway
      agencies to create effective traffic management plans (TMP) for work zones
      quantitatively and objectively.

PMID- 15243950
TI  - A neural-network approach for visual cryptography and authorization.
AB  - In this paper, we propose a neural-network approach for visual authorization,
      which is an application of visual cryptography (VC). The scheme contains a key
      share and a set of user-shares. The administrator owns the key-share, and each
      user owns a user-share issued by the administrator from the user-share set. The
      shares in the user-share set are visually indistinguishable, i.e. they have the
      same pictorial meaning. However, the stacking of the key-share with different
      user-shares will reveal significantly different images. Therefore, the
      administrator (in fact, only the administrator) can visually recognize the
      authority assigned to a particular user by viewing the information appearing in
      the superposed image of key-share and user-share. This approach is completely
      different from traditional VC approaches. The salient features include: (i) the
      access schemes are described using a set of graytone images, and (ii) the
      codebooks to fulfil them are not required; and (iii) the size of share images is
      the same as the size of target image.

PMID- 15243949
TI  - Software reliability prediction using recurrent neural network with Bayesian
      regularization.
AB  - A recurrent neural network modeling approach for software reliability prediction
      with respect to cumulative failure time is proposed. Our proposed network
      structure has the capability of learning and recognizing the inherent internal
      temporal property of cumulative failure time sequence. Further, by adding a
      penalty term of sum of network connection weights, Bayesian regularization is
      applied to our network training scheme to improve the generalization capability
      and lower the susceptibility of overfitting. The performance of our proposed
      approach has been tested using four real-time control and flight dynamic
      application data sets. Numerical results show that our proposed approach is
      robust across different software projects, and has a better performance with
      respect to both goodness-of-fit and next-step-predictability compared to existing
      neural network models for failure time prediction.

PMID- 15243951
TI  - Complexity of error hypersurfaces in multilayer perceptrons.
AB  - Error hypersurfaces are very valuable to study because of their unique status in
      multilayer perceptron research. Given the architecture of a multilayer
      perceptron, if the pattern sets are different, so are the respective error
      hypersurfaces in the multilayer perceptron. Using the theory of groups and Polya
      Theorem, this paper constructs classes of congruent pattern sets and classes of
      congruent error hypersurfaces, and proves that the number of classes of congruent
      pattern sets is equal to the number of congruent error hypersurfaces. Calculation
      results lead to much fewer classes of congruent error hypersurfaces than the
      total error hypersurfaces, and show that as the input dimension N increases, the
      former number increases at a much lower rate than the latter number, thus
      simplifying the understanding of the complexity of classes of error
      hypersurfaces.

PMID- 15243952
TI  - Efficient training of RBF networks for classification.
AB  - Radial Basis Function networks with linear outputs are often used in regression
      problems because they can be substantially faster to train than Multi-layer
      Perceptrons. For classification problems, the use of linear outputs is less
      appropriate as the outputs are not guaranteed to represent probabilities. We show
      how RBFs with logistic and softmax outputs can be trained efficiently using the
      Fisher scoring algorithm. This approach can be used with any model which consists
      of a generalised linear output function applied to a model which is linear in its
      parameters. We compare this approach with standard non-linear optimisation
      algorithms on a number of datasets.

PMID- 15243953
TI  - On the limit cycle structure of threshold boolean networks over complete graphs.
AB  - In previous work, the limit structure of positive and negative finite threshold
      boolean networks without inputs (TBNs) over the complete digraph K(n) was
      analyzed and an algorithm was presented for computing this structure in
      polynomial time. Those results are generalized in this paper to cover the case of
      arbitrary TBNs over K(n). Although the limit structure is now more complicated,
      containing, not only fixed-points and cycles of length 2, but possibly also
      cycles of arbitrary length, a simple algorithm is still available for its
      determination in polynomial time. Finally, the algorithm is generalized to cover
      the case of symmetric finite boolean networks over K(n).

PMID- 15243955
TI  - Program funding. HIV, other social programs likely losers from tax cuts.

PMID- 15243954
TI  - Highlight issue on glycobiology dedicated to the memory of Victor Ginsburg.

PMID- 15243956
TI  - Military successfully reduces HIV-positive sailor's disability.

PMID- 15243957
TI  - Court says HIV is occupational hazard for prison officials.

PMID- 15243958
TI  - Parental rights. Child's viral load insufficient to strip mother of rights.

PMID- 15243959
TI  - Court-ordered HIV testing upheld for child molester.

PMID- 15243960
TI  - SSA. HIV-positive man ordered to repay SSI benefits.

PMID- 15243962
TI  - Award. Group honored as pioneer in developing world health.

PMID- 15243961
TI  - Hemophilic attorneys win judgment against lawyer.

PMID- 15243963
TI  - Treating primary HIV infection: HIV and the US sex-film industry.

PMID- 15243964
TI  - Oroesophageal candidiasis in a patient with AIDS.

PMID- 15243965
TI  - The HIV pandemic: the power of acting early.

PMID- 15243966
TI  - Anemia prevalence and associated risk factors in a single-center ambulatory HIV
      clinical cohort.
AB  - The prevalence of anemia in HIV-infected persons has not been well characterized
      in the HAART era. In a single-center, retrospective study, anemia prevalence and
      risk factors, including use of HAART, were assessed in an ambulatory clinical
      cohort of 758 HIV-infected patients for the calendar year 2000. The relationships
      between anemia (hemoglobin level less than 12.5 g/dL) and demographic variables,
      antiretroviral treatment regimens, and disease markers were analyzed. Mean
      baseline patient characteristics were hemoglobin level, 13.7 +/- 1.9 g/dL; CD4+
      cell count, 405 +/- 293/microL; and HIV RNA level, 77,841 +/- 148,394 copies/mL.
      Overall anemia prevalence was 30.3%. Multivariate logistic regression analysis
      demonstrated that anemia was associated with a CD4+ cell count below 50/microL,
      female sex, black race, a viral load above 100,000 copies/mL, zidovudine use, and
      older age. Severe anemia was less prevalent in this study population than in
      historical comparators; however, mild to moderate anemia rates remain high.

PMID- 15243967
TI  - Editorial comment: HAART and higher hemoglobin levels.

PMID- 15243968
TI  - Impact of once- and twice-daily dosing regimens on adherence and overall safety.
AB  - Low-frequency dosing regimens are the best options for long-term HAART with
      regard to convenience, adherence, and efficacy. In a drive to simplify HIV
      treatment, once-daily dosing has been advocated as more effective than twice
      daily dosing at maintaining adherence and, therefore, controlling viral load.
      However, there are only a limited number of systematic studies comparing the
      safety and efficacy of such regimens. This review presents an overview of reduced
      frequency dosing regimens from recent HAART trials and critically examines the
      factors related to adherence and therapeutic efficacy. Clinical data to guide
      individual treatment decisions are limited, and therapy--whether a once-daily,
      twice-daily, or other dosing schedule--should be selected based on individual
      patient needs.

PMID- 15243970
TI  - [16th mixed meeting Inserm-SNFMI. Pulmonary arterial hypertension].

PMID- 15243969
TI  - Editorial comment: thoughts on the once-daily-dosing bandwagon.

PMID- 15243971
TI  - Remifentanil produces vasorelaxation in isolated rat thoracic aorta strips.

PMID- 15243973
TI  - Read the instructions.

PMID- 15243974
TI  - Characterizing HPLC stationary phases.

PMID- 15243972
TI  - Physiology: does gut hormone PYY3-36 decrease food intake in rodents?
AB  - Batterham et al. report that the gut peptide hormone PYY3-36 decreases food
      intake and body-weight gain in rodents, a discovery that has been heralded as
      potentially offering a new therapy for obesity. However, we have been unable to
      replicate their results. Although the reasons for this discrepancy remain
      undetermined, an effective anti-obesity drug ultimately must produce its effects
      across a range of situations. The fact that the findings of Batterham et al.
      cannot easily be replicated calls into question the potential value of an anti
      obesity approach that is based on administration of PYY3-36.

PMID- 15243975
TI  - The single-cell scene.

PMID- 15243976
TI  - And the Oscar goes to...

PMID- 15243977
TI  - Micellar electrokinetic chromatography.

PMID- 15243978
TI  - Finding acrylamide.

PMID- 15243980
TI  - Adequate literacy and health literacy: prerequisites for informed health care
      decision making.

PMID- 15243979
TI  - Involvement of oxidative stress in the profibrotic action of aldosterone.
      Interaction wtih the renin-angiotension system.
AB  - BACKGROUND: The aim of this study was to investigate the involvement of
      angiotensin II and oxidative stress on cardiovascular damage induced by chronic
      subcutaneous aldosterone infusion in the absence of salt loading. METHODS:
      Sprague-Dawley rats were infused with d-aldosterone (0.75 microg/h
      subcutaneously) for 6 weeks. Blood pressure was measured with the tail-cuff
      method. Small arteries were investigated on a pressurized myograph.
      Cardiovascular and renal collagen was evaluated by Sirius red staining. Systemic
      oxidant excess was measured with plasma 8-isoprostane by ELISA and by measurement
      of thiobarbituric acid-reactive substances. Vascular reactive oxygen species were
      studied using hydroethidine and NADPH-generated superoxide anion measured by
      lucigenin chemiluminescence. RESULTS: After 6 weeks of treatment, systolic blood
      pressure was significantly increased in aldosterone-infused rats (170+/-8 v 123+/
      2 mm Hg in controls, P < .05). Progression of hypertension was partially
      prevented by co-administration of losartan (AT1 receptor blocker) or tempol
      (superoxide dismutase mimetic): 140+/-4 and 149+/-6 mm Hg, respectively, P < .05
      versus the aldosterone group. Aldosterone induced renal but not cardiac
      hypertrophy, which was not prevented by losartan or by tempol. Moreover, losartan
      and tempol failed to prevent vascular hypertrophy of resistance mesenteric
      vessels. However, losartan (0.77%+/-0.05%) and tempol (0.65%+/-0.10%) prevented
      cardiac fibrosis in the midmyocardium in the aldosterone group (1.03%+/-0.12% v
      0.68%+/-0.07% positive staining per area in control, P < .05). In the kidney,
      collagen accumulation of aldosterone-infused rats was also significantly
      decreased by losartan (-77%) and tempol (-60%). Similar effects were obtained on
      aortic fibrosis. Aldosterone increased serum 8-isoprostane levels.This increase
      was blunted by losartan and tempol. Losartan and tempol totally prevented
      vascular, cardiac, and renal increase of NADPH-induced superoxide production
      stimulated by aldosterone. CONCLUSIONS: Our data suggest that the profibrotic but
      not the hypertrophic action of aldosterone are mediated at least in part by
      reactive oxygen species generation and involve an interaction with the renin
      angiotensin system.

PMID- 15243981
TI  - Nutrition labeling at fast-food and other chain restaurants.

PMID- 15243982
TI  - Glutathione synthetase deficiency associated with antenatal cerebral bleeding.
AB  - We present a newborn with glutathione synthetase deficiency and intracranial
      haemorrhages. Because the latter are rare in term newborns a possible
      relationship with glutathione synthetase deficiency will be discussed.

PMID- 15243983
TI  - A Japanese case with inosine triphosphate pyrophosphohydrolase deficiency
      attributable to an enzymatic defect in white blood cells.
AB  - Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is characterized by
      abnormal accumulation of inosine triphosphate. We describe the first Japanese
      case with ITPase deficiency and demonstrate that the deficiency of ITPase
      activity is not only found in erythrocytes but also in white blood cells.

PMID- 15243984
TI  - A novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome
      detected by neonatal screening for galactosaemia.
AB  - A patient affected by Fanconi-Bickel syndrome detected by neonatal screening for
      galactosaemia is reported. Molecular studies of the GLUT2 gene led to the
      identification of a novel mutation of the glucose transporter.

PMID- 15243985
TI  - Mitochondrial respiratory chain disease presenting as progressive bulbar
      paralysis of childhood.
AB  - We report two siblings with a mitochondrial respiratory chain defect who
      presented with progressive bulbar paralysis of childhood (Fazio-Londe disease).
      Mitochondrial respiratory chain defects should be considered in differential
      diagnosis of this rare clinical entity.

PMID- 15243986
TI  - Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man
      and family studies.
AB  - Ornithine transcarbamylase deficiency (OTCD) resulting from deficiency of the
      mitochondrial enzyme OTC shows extensive phenotypic heterogeneity influenced by
      allelic heterogeneity and modifying environmental influences such as protein
      intake. We report the fatal late-onset presentation of OTCD in a 62-year-old man
      with the V337L mutation, a previous presentation in his grandson and negative
      clinical and biochemical screening of the proband's three daughters.

PMID- 15243987
TI  - Carrier screening for Canavan disease in Australia.
AB  - This study reports, for the first time, the carrier frequency of Canavan disease
      in the Ashkenazi Jewish population in Australia, and the identification of a
      novel mutation in the ASPA gene.

PMID- 15243989
TI  - Sedation with 4-hydroxybutyric acid: a potential pitfall in the diagnosis of
      SSADH deficiency.
AB  - Deficiency of succinic semialdehyde dehydrogenase (SSADH) is a rare
      neurometabolic disorder with accumulation of 4-hydroxybutyric acid (4-HBA) as a
      biochemical hallmark. We present a boy with an unresolved severe neurological
      disorder and intermittent elevation of 4-HBA in serum and CSF which was later
      shown to result from iatrogenic administration of 4-HBA for sedation purposes.

PMID- 15243988
TI  - [A structured treatment and educational program for patients with type 2 diabetes
      mellitus, insulin therapy and impaired cognitive function (DikoL)].
AB  - BACKGROUND AND PURPOSE: More than 50% of patients with type-2 diabetes mellitus
      and impaired cognitive function are overtaxed with some topics of established
      structured treatment and teaching programs for patients with insulin therapy.
      This leads to substantial deficits in respect of the patients' ability of
      diabetes self-management (insulin injections, self-monitoring) and the need for
      help by relatives and social workers. The consequences are an impaired quality of
      life and a great deal of expense in the welfare system. Since 1996, a specialized
      structured treatment and teaching program for patients with type-2 diabetes
      mellitus, insulin therapy, and impaired cognitive function (DikoL) has been
      developed. Main differences in comparison to established programs were less
      theoretical topics (no pathophysiology, no insulin action, no complicated
      calculation of carbohydrate pounds) and more time for practical exercise. In a
      randomized prospective study, the effectiveness of the DikoL program was
      evaluated. PATIENTS AND METHODS: All patients with type-2 diabetes mellitus (n =
      106, age 68.6 +/- 8.7 years, median diabetes duration 10.3 [0.03-35.4] years,
      HbAlC 10.3+ 1.7% [HPLC, Diamat, normal range 4.5-6.3%], cognitive function 87.7
      +12.3 IQ points), admitted to hospital to participate in a structured treatment
      and teaching program between April 1999 and June 2000, were studied. Patients
      with impaired cognitive function (< 91 IQ points) were randomized: they
      participated either in an established structured treatment and teaching program
      according to Berger et al. (standard group: n = 35) or in the DikoL program(DikoL
      group: n = 33). Immediately after participation and 0.5 years later, the quality
      of diabetes control, patients' knowledge of diabetes, their ability for diabetes
      self-management, and their satisfaction with the program were evaluated. RESULTS:
      Patients of the DikoL group had a comparable quality of diabetes control (HbAlc:
      DikoL vs. standard group: 8.5 + 1.3 vs. 8.3 +/- 1.4%; p = 0.62)and diabetes
      related knowledge (DikoL vs. standard group: 9.6 +/- 4.4 vs.10.3 + 3.8 points; p
      = 0.52), but significantly better results in respect of their ability for
      diabetes self-management (DikoL vs. standard group: 15.9 +/- 3.1 vs. 12.5 +/- 4.1
      points; p = 0.001) than patients of the standard group. Moreover, in the DikoL
      group there was a tendency to a lower number of patients needing third-party
      assistance (n = 1 patient of the DikoL group vs. n = 5 patients of the standard
      group; p = 0.13). There were no acute complications (hypoglycemia, comata, and
      foot ulcers) in neither group. Following participation in the DikoL program,
      patients reached a better score in the questionnaire evaluating satisfaction with
      the treatment and teaching program (DikoL vs. standard group:52.5 + 4.5 vs. 44.7
      + 76 points; p < 0,001). CONCLUSION: Following the wishes of the majority of
      diabetes educators as well as diabetologists but also patients' wishes, a
      specially designed structured treatment and teaching program for patients with
      type-2 diabetes mellitus, insulin therapy, and impaired cognitive function was
      designed. DikoL is the first program evaluated in a randomized, prospective
      trial. It clearly demonstrated a bet-ter outcome for patients with impaired
      cognitive function in respect of diabetes self-management and satisfaction. With
      its implementation, patients' quality of diabetes care can be improved in a
      substantial manner.

PMID- 15243990
TI  - Medicare cards: no match for online prices.

PMID- 15243991
TI  - The early-onset phenotype of mitochondrial trifunctional protein deficiency: a
      lethal disorder with multiple tissue involvement.
AB  - Mitochondrial trifunctional protein (TFP) deficiency is a clinically
      heterogeneous disorder with phenotypes of different severity. Early onset, severe
      forms predominantly exhibit cardiomyopathy, life-threatening arrhythmias and
      liver dysfunction; the later-onset, milder phenotype is mainly characterized by
      neuromyopathic features. The mechanisms that determine these heterogeneous
      presentations are unknown. We performed multiple tissue immunoblots from a
      patient with early-onset, lethal TFP deficiency and demonstrated absent TFP
      antigen in all. The predominant cardiac manifestation of severe TFP deficiency
      reflects its essential role in myocardial energetics, not its tissue-specific
      expression.

PMID- 15243992
TI  - The trouble with recalls.

PMID- 15243993
TI  - Designer eggs: best way to get your omega-3 fatty acids?

PMID- 15243994
TI  - Acute metabolic crisis with extreme deficiency of glutathione in combination with
      decreased levels of leukotriene C4 in a patient with glutathione synthetase
      deficiency.
AB  - A 32-year-old man with glutathione synthetase deficiency developing an acute
      metabolic crisis is described. During this acute episode, intracellular
      glutathione content in erythrocytes was below the detection limit (<0.3 mmol/L).
      Leukotriene C4 in CSF and urinary leukotriene E4 were massively decreased,
      indicating an imparied synthesis of cysteinyl leukotrienes. Clinical recovery
      after one week was accompanied by a clear improvement of these biochemical
      parameters. The highly disturbed glutathione synthesis is postulated to be the
      reason for a deficient synthesis of cysteinyl leukotrienes, which may at least in
      part be responsible for the severe clinical symptoms.

PMID- 15243995
TI  - Biobanks: simplifying consent.

PMID- 15243996
TI  - Aortic dissection in Turner syndrome.

PMID- 15243997
TI  - Parents' satisfaction with medical and social assistance provided to children
      with Down syndrome: experience in Estonia.
AB  - OBJECTIVE: Parents of children with mental or physical disabilities have been
      assumed to live more stressful lives than other parents, and people with Down
      syndrome (DS) may get second-rate care because of their diagnosis. The aim of
      this work is to investigate the extent of parents' satisfaction with medical and
      social services in Estonia provided for the DS individuals and their families.
      METHODS: From 1999 to 2001, fifty-nine DS families answered questionnaires in
      which we inquired about their satisfaction with medical and social assistance.
      RESULTS: We found that satisfaction with the quality of the information about DS
      is low, and most of the parents are not satisfied with the social benefits and
      rehabilitation options. CONCLUSIONS: The DS families need more medical
      information about this syndrome. The medical staff has to learn more about how to
      deliver bad news and how to support parents. More work needs to be done in the
      area of rehabilitation options and social assistance.

PMID- 15243998
TI  - Peptide aptamers: tools for biology and drug discovery.
AB  - Peptide aptamer technology is relatively youthful. It has the advantage over
      existing techniques that the reagents identified are designed for expression in
      eukaryotic cells. This allows the construction of molecular tools that allow the
      logic of genetics, from knockouts to extragenic suppressors, to be applied to
      studies of proteins in tissue culture cells. Until recently, the available tools
      have limited our understanding of cell biology. The same limitation restricts out
      ability to validate the numerous candidate drug targets emerging from genome-wide
      approaches to cellular biology. Peptide aptamers represent a stride forwards in
      the evolution of a modular, molecular tool kit for cell biology and for drug
      target validation. The authors predict that they will also play a role in the
      transition from genomic to proteomic microarray technology.

PMID- 15243999
TI  - Principles of managing the radiotherapy patient.

PMID- 15244000
TI  - Osteonecrosis: a multifactorial etiology.

PMID- 15244001
TI  - Tooth in the line of fracture.

PMID- 15244002
TI  - Condylar position in disc displacement.

PMID- 15244003
TI  - Ultra-high molecular weight polyethylene fossa wear and incidence of adverse
      effects.

PMID- 15244004
TI  - A plea for precise terminology.

PMID- 15244005
TI  - [General mobilization to face challenge of Alzheimer's disease].

PMID- 15244006
TI  - Paul Francis Wehrle.

PMID- 15244007
TI  - Effect of individual shades on reliability and validity of observers in colour
      matching.
AB  - The effect of individual shades in shade guides, on the reliability and validity
      of measurements in a colour matching process is very important. Observer's
      agreement on shades and sensitivity/specificity of shades, can give us an
      estimate of shade's effect on observer's reliability and validity. In the present
      study, a group of 16 students, matched 15 shades of a Kulzer's guide and 10 human
      incisors to Kulzer's and/or Vita's shade tabs, in 4 different tests. The results
      showed shades I, B10, C40, A35 and A10 were those with the highest reliability
      and validity values. In conclusion, a) the matching process with shades of
      different materials was not accurate enough, b) some shades produce a more
      reliable and valid match than others and c) teeth are matched with relative
      difficulty.

PMID- 15244008
TI  - A modern day application of the Rochette bridge.
AB  - A restoration that is frequently prescribed to provisionally restore the single
      unit edentulous space is the removable acrylic partial prosthesis. The Rochette
      bridge design provides an effective alternative when confronted with this
      clinical situation. The adaptable nature of this technique means that it can be
      utilised in a variety of clinical situations with success. The greatest benefits
      are seen in clinical situations where simple and aesthetic alteration of the
      pontic dimensions during treatment is necessary. It can also be used in long-term
      provisional situations where, if a removable acrylic partial prosthesis was used,
      multiple adjustments or remakes would be necessary. This paper presents three
      case reports where this technique has been utilised with distinctive advantages
      over a provisional removable partial acrylic prosthesis.

PMID- 15244009
TI  - Systemic antibiotics in the management of chronic periodontitis.
AB  - Multiple research studies have investigated the use of systemic antibiotics as
      adjunctive treatments in the management of chronic periodontitis. However, the
      great heterogeneity of study designs and variable outcomes that have been
      reported have led to confusion among the profession as to whether or not there is
      any clinical benefit of using systemic antibiotics. In this review, the potential
      advantages and disadvantages of using systemic antibiotics are considered
      together with outcomes from published clinical studies. Few published studies are
      of adequate quality to be considered in systematic reviews, and the outcomes are
      very varied. Drawing definitive conclusions is difficult, but given the lack of
      reliable data available, systemic antibiotics cannot be indicated as adjuncts in
      the treatment of chronic periodontitis.

PMID- 15244010
TI  - Prosthetic dentistry and the unilateral cleft lip and palate patient. The last 30
      years. A review of the prosthodontic literature in respect of treatment options.
AB  - All cleft lip and palate patients are unique and present with their own
      diagnostic and prosthodontic problems. Many patients have benefited, recently,
      from alveolar bone grafting and orthodontic realignment and require little or no
      prosthodontic treatment. Some treatment, however, has been planned with a
      prosthesis as the final restoration, as a sizeable number of such patients have
      not undergone the alveolar graft procedure, (or this has been unsuccessful), or
      they were deemed to be unsuitable because of the extent of their defect. The
      patients who have not received grafting and orthodontic realignment are therefore
      the patients who present the greatest prosthodontic challenge. This paper
      presents an overview of the work that has been carried out over the last thirty
      years in relation to the prosthodontic rehabilitation of the cleft lip and palate
      patient. It is clear that multidisciplinary treatment planning by surgeons,
      orthodontists and restorative dentists is required for the long-term benefit of
      this small but challenging group of patients.

PMID- 15244011
TI  - Flexural properties of prosthetic provisional polymers.
AB  - In this in-vitro study, the flexural strength and Young's-modulus of five resin
      based provisional materials were compared after repair. A three-point bending
      test and a fracture test of 3-unit fixed partial dentures (FPDs) were performed.
      Temphase (53.1 +/- 7.9 MPa), Luxatemp (45.2 +/- 7.8 MPa) and Trim (17.8 +/- 2.5
      MPa) showed significantly lower initial flexural strength compared to Provipont
      (54.3 +/- 10.5 MPa) and Protemp 3 Garant (58.9 +- 5.9 MPa). A significant
      decrease of flexural strength was found after the repair of Luxatemp and Temphase
      with provisional material on the oxygen-inhibited surface, and additionally, for
      Temphase with composite on mill-cut surface. The fracture strength of the FPDs
      varied between 655N for Trim and 1258N for Protemp3. After the repair, the
      results did not change significantly. The effectiveness of the repair using
      temporary materials was highly dependent on the type of material and the repair
      material. However, the repair of the FPDs with provisional resin may lead to
      minor changes in the fracture resistance. The high flexural strength and fracture
      resistance would favor Protemp3 and Provipont for long term clinical application.

PMID- 15244012
TI  - An in vitro investigation of bond strength of veneering composite resin to glass
      fibre veil reinforced composite.
AB  - Experimental light-curing polymer-monomer-gel-impregnated E-glass-fibre veil
      reinforced composite (i.e. a composite with randomly oriented fibres) was used as
      an adhesional substrate for veneering composite resin (VCR). Continuous
      unidirectional glass fibre composite was used as a control substrate. Both the
      fibre-reinforced composite substrate surfaces were ground or, optionally, the
      substrate surface was left untreated (containing oxygen-inhibited resin layer)
      before attaching to the VCR. No adhesive resin was used between the composites.
      Shear bond strength of VCR to the substrate was determined for dry and
      thermocycled specimens. The results of this study suggested that the VCR can
      better be bonded to the randomly oriented veil fibre-reinforced composite
      substrate than to the continuous unidirectional fibre-reinforced composite
      substrate.

PMID- 15244013
TI  - Comparison of cetraxate-based and pantoprazole-based triple therapies in the
      treatment of Helicobacter pylori infection.
AB  - BACKGROUND: Recent studies suggest that cetraxate possesses anti-Helicobacter
      pylori (H. pylori) activity. We therefore conducted this pilot study to
      investigate the efficacy of a cetraxate-based triple therapy and to compare the
      regimen with proton pump inhibitor-based triple therapy. METHODS: From April 2001
      to January 2002, a total of 58 H. pylori-infected patients were randomly assigned
      to 1 of 2 regimens for 1 week: cetraxate plus clarithromycin and amoxicillin (CCA
      group) or pantoprazole plus clarithromycin and amoxicillin (PCA group). Follow-up
      endoscopy was performed at 8 weeks after the end of treatment to assess the
      treatment response. RESULTS: Intention-to-treat analysis showed that the
      eradication rates of the CCA group (n = 27) and PCA group (n = 31) were 70.4% and
      93.5%, respectively. The CCA group had a significantly lower eradication rate
      than the PCA group (p = 0.03). Per-protocol analysis also showed similar results
      (69.2% vs. 96.7%, p = 0.01). However, the frequency of adverse events in the CCA
      group was lower than that of the PCA group (3.7% vs. 25.8%, p = 0.03). Univariate
      analysis showed that the eradication rate was significantly related to proton
      pump inhibitor therapy (93.5% vs. 70.4%, p = 0.03 ) and smoking habit (66.7 % vs.
      88.4%, p = 0.05), but multivariate analysis disclosed that proton pump inhibitor
      therapy was the only independent factor predicting treatment success (p < 0.05).
      CONCLUSIONS: Cetraxate-based triple therapy is less effective than pantoprazole
      based triple therapy in the treatment of H. pylori infection. However, the former
      has a lower frequency of adverse effects than the latter.

PMID- 15244014
TI  - Comparing the clinical outcomes of intrauterine insemination by two different
      density gradient preparation methods.
AB  - BACKGROUND: Sperm preparation has play an integral part in the success of in
      vitro fertilization. The aim of this study was to compare 2 different density
      gradient preparations for sperm separation in respect to sperm recovery,
      motility, motion parameters and clinical outcome after intrauterine insemination.
      METHODS: One-hundred and 21 women who received intrauterine insemination due to
      ovulation dysfunction were randomly allocated into 2 groups, using either the
      Percoll (Amersham, Pharmacia Biotech AB, Sweden) or the PureSperm (Nidacon,
      Goteborg, Sweden) density gradient method for sperm preparation. The
      characteristics of sperm before and after separation and the clinical outcome of
      intrauterine insemination were compared between the 2 groups. RESULTS: PureSperm
      and Percoll demonstrated comparable ability to recover the sperms with
      progressive motility. There was no difference in motion parameters and the number
      of sperm recovered with progressive motility between the Percoll and the
      PureSperm density gradient preparations. The clinical pregnancy rate was also
      comparable between the 2 groups, 12.5% (7/56) in the PureSperm group compared to
      13.8% (9/65) in the Percoll group, (p > 0.05). CONCLUSIONS: Despite using
      different density composition and volume, PureSperm demonstrated clinical effect
      comparable to that of Percoll in preparing sperm for intrauterine insemination.

PMID- 15244015
TI  - Managements of locally advanced unresectable thymic epithelial tumors.
AB  - BACKGROUND: Surgery is the treatment of choice for thymic epithelial tumors
      (TET), but the resectability is about 60-70%. For those with locally advanced
      unresectable TETs (LAU-TETs), some controversies about the prognostic factors and
      treatment modalities existed. The aims of this study are to elucidate the roles
      of various therapeutic options and to determine the survival and prognostic
      factors of LAU-TETs. METHODS: Twenty-seven patients diagnosed with LAU-TETs
      underwent treatment in Taipei Veterans General Hospital between 1979 and 1997.
      Multiple treatment modalities, including surgical intervention, irradiation and
      chemotherapy, were advocated for these patients. The clinicopathological factors
      and the effects of the treatment modalities were evaluated retrospectively.
      RESULTS: Twenty seven cases of LAU-TETs, included 18 thymomas (12 at stage III
      and 6 at stage IVa) and 9 thymic carcinomas (4 at stage III and 5 at stage IVa),
      were enrolled for study. The overall 5-year and 10-year survival rates were 54.6%
      and 35.1%, respectively. Patients receiving debulking surgery and those with
      irradiation dosage higher than 4400 cGy had significantly better survivals (P =
      0.021 and P = 0.016, respectively). CONCLUSIONS: Aggressive debulking surgery and
      sufficient irradiation dosage provide better survivals for patients with LAU
      TETs, especially for those with thymoma.

PMID- 15244016
TI  - Voice acoustic analysis of normal Taiwanese adults.
AB  - BACKGROUND: Because of advances in voice research, voice acoustic analysis
      including fundamental frequency (F0), sound pressure level (SPL), jitter,
      shimmer, harmonics-to-noise ratio (H/N ratio), and maximum phonation time (MPT)
      can now be easily recorded and analyzed with a computer. Because these systems
      are widely used in clinical practice, this study was designed to establish the
      normal acoustic analysis parameters in normal Taiwanese adults. METHODS: From
      Mar. 2002 to Dec. 2002, 45 Taiwanese women and 45 Taiwanese men younger than 50
      years old were recruited as subjects for this study. The commercially available
      Computer Speech Lab and Aerophone II system manufactured by Kay Elemetrics Corp.
      were used to record the aforementioned acoustic data under comfortable phonation.
      Each gender was separated equally into 3 age subgroups. Then differences between
      gender and age subgroups were investigated by statistics software SPSS 10.0. Our
      results were compared with data from previous reports. RESULTS: The value of F0
      (counting; vowel /a/) was greater for females (203.2 +/- 21.7; 213.4 +/- 25.4 Hz)
      than for males (118.3 +/- 17.3; 121.3 +/- 16.4 Hz). Conversely, the value of MPT
      was greater for males (28.0 +/- 9.4 sec) than for females (22.6 +/- 7.6 sec).
      There were no significant differences in average SPL and jitter between female
      (77.8 +/- 5.5 dB; 0.66 +/- 0.27%) and male (77.5 +/- 5.5 dB; 0.56 +/- 0.23%)
      subgroups. Except for shimmer and H/N ratio in the male subgroup, there were no
      differences in parameters within both gender subgroups with respect to age.
      CONCLUSIONS: We have developed a body of normal data for various parameters of
      acoustic analysis in different age groups and genders. It seems that the majority
      of voice characteristics of adults were relatively stable and did not change with
      aging between 20 and 49. But the shimmer and H/N ratio were variable in different
      genders and age groups. However, the voice characteristics of adults older than
      50 years old were not recorded in this study and therefore require further
      investigation.

PMID- 15244017
TI  - Do we get a "real" alignment of knee in the preoperative planning of high tibia
      osteotomy: a prospective study of reproducibility.
AB  - BACKGROUND: Precise preoperative measurement of knee alignment is needed to
      calculate the accurate angle of correction at proximal tibia osteotomy for medial
      gonarthrosis. METHODS: We performed a prospective study to compare the
      reproducibility of measuring the mechanical and anatomical axes. Thirty-two
      patients (32 knees) with medial compartment osteoarthritis to be treated with
      proximal tibia osteotomy were included in this study. Preoperatively, whole lower
      limb roentgenographs were obtained twice, and 2 independent radiologists measured
      the mechanical and anatomical axes from each roentgenograph. RESULTS: Measurement
      of mechanical and anatomical axes had a mean variability of 2.22 and 1.88
      degrees, respectively, which was not statistically significant (p = 0.267) in the
      assessment of reproducibility. With the anatomic axis, however, we found 0.61
      degree of variability to the roentgenographic procedures and 1.30 degree to the
      radiologists (p = 0.007). With the mechanical axis, the corresponding findings
      were 1.30 degree and 1.02 degree (p = 0.167). Despite the relative small number
      of patients in this series, errors in measurement of the anatomical axis seem
      mostly to originate from different radiologists, whereas errors in measurement of
      the mechanical axis seem to originate from both the radiologists and the
      procedures. The maximum variability in measuring both axes was 3 degrees, which
      is highly significant for a reliable calculation of the wedge when performing
      proximal tibia osteotomy. CONCLUSIONS: We suggest that, for accuracy and economy,
      measurement of the anatomical axis might be better. Furthermore, by measuring
      either mechanical or anatomical axis, the errors originating from
      roentgenographic measurement of knee alignment should be considered in
      preoperative planning.

PMID- 15244018
TI  - Endovascular stenting treatment for drug-refractory hypertension due to ostial
      stenosis of transplanted renal artery.
AB  - Transplanted renal artery stenosis (TRAS) is one of the major causes of poor
      blood pressure control, progressive renal dysfunction and finally renal graft
      failure in uremic patients receiving renal allograft transplantation.
      Percutaneous transluminal balloon angioplasty (PTA) with stenting is an effective
      treatment for TRAS but has rarely had validation for the ostial lesions of TRAS.
      We reported 2 patients developing drug-refractory hypertension along with
      impaired renal function who received PTA plus stent deployment therapy for severe
      ostial stenosis of graft renal artery. Both of the patients had improved
      allograft function gradually, and satisfactory blood pressure control after 3
      months follow-up. In conjugation with balloon angioplasty, stenting could provide
      a safe and effective revascularization strategy in conjunction with balloon
      angioplasty for ostial lesions of TRAS.

PMID- 15244019
TI  - Acquired fanconi syndrome induced by mixed Chinese herbs presenting as proximal
      muscle weakness.
AB  - We report a rare case with acquired Fanconi syndrome caused by mixed Chinese
      herbs, initially presenting as waddling gait and lower limb muscle atrophy. From
      a series of investigations, proximal renal tubule injury with functional defects
      and Chinese herb nephropathy were discovered. Hypophosphatemic osteomalacia and
      type II muscle fiber atrophy shown in muscle biopsy of left quadriceps may be
      associated with the sequelae of ingestion of mixed crude Chinese herbs.
      Aggressive and early alkali treatment with supplementation of phosphate and
      Vitamin D restored the patient's metabolic and musculoskeletal abnormalities.

PMID- 15244020
TI  - Continuous abdominal paracentesis for management of late type severe ovarian
      hyperstimulation syndrome.
AB  - The ovarian hyperstimulation syndrome (OHSS) is often observed in patients
      undergoing assisted reproductive technology (ART). In severe form OHSS is a
      serious and potentially life-threatening. Here we report a 36-year-old woman with
      primary infertility due to endometriosis who underwent controlled ovarian
      hyperstimulation. Ten days later, severe late-onset ovarian hyperstimulation
      syndrome, severe ascites and pulmonary effusion, developed. Continuous abdominal
      paracentesis of 5000 mL/day was performed on the third day. With this procedure,
      ascitic fluid was drained efficiently and the patient's condition improved. This
      report suggests that early continuous abdominal paracentesis with drainage of
      ascitic fluid is an efficacious procedure for management of the severe ovarian
      hyperstimulation syndrome as soon as euvolemia is achieved clinically.

PMID- 15244021
TI  - Nasopharyngeal carcinoma spreading along the eustachian tube: the imaging
      appearance.
AB  - Nasopharyngeal cancer (NPC) is one of the most common cancers in Taiwan. It can
      spread anteriorly, laterally, posteriorly, superiorly and inferiorly. Skull base
      invasion is the common presentation, in up to one-third of cases. We report a
      rare spreading pathway of NPC, via the eustachian tube. A 44-year-old male
      suffered from NPC and got radiotherapy about 2 years ago. He suffered from middle
      ear effusion and facial nerve palsy on the right side recently. The computed
      tomography and magnetic resonance image could clearly depict the infiltrating
      tumor over the mastoid region and tympanic cavity on the right side, spreading
      along the eustachian tube. It could result in eustachian tube dysfunction and
      middle ear effusion. The nature of the right facial palsy was most likely due to
      tumor infiltration.

PMID- 15244022
TI  - Lymphangioma of male exogenital organs.
AB  - Lymphangioma manifesting in the genitourinary tract is an uncommon disease.
      Cystic lymphangioma is a congenital lymphatic hamartoma known as lymphatic
      malformation. Herein we report 2 cases of lymphangioma of male exogenital organs.
      After complete excision of the tumor and subsequent follow-up for 6 months, both
      of them were free of recurrence. Ultrasonography and computed tomography scans
      are very useful in the differential diagnosis of this cystic disease.

PMID- 15244023
TI  - [Clinical practice guidelines: surgical treatment of tympanic membrane
      perforations in children].
AB  - A study group emanating from the French Society of Otolaryngologists and
      Associated Paediatric Otologists, anaesthetists and bacteriologists carried out a
      review of the world literature regarding the indications, technique and results
      of simple myringoplasty in children. The group assessed the levels of evidence
      present in published articles and the opinions of experts in the field, due to
      the lack of sufficient evidence. The study group then established recommendations
      for good practice. These were sent to otolaryngologists, paediatricians, general
      practitioners and anaesthetists involved in the care of children under the age of
      15 presenting with a simple non-infected tympanic membrane perforation and
      without affection of the ossicular chain. The full text of the recommendations is
      provided.

PMID- 15244024
TI  - A clinico-radiological study of the contralateral ear in acquired unilateral
      cholesteatoma.
AB  - OBJECTIVE: Clinico-audiological and CT scan assessments of the contralateral ear
      in patients with unilateral cholesteatoma can be a good predictive method for the
      fate of these ears. MATERIAL AND METHODS: Fifty patients with unilateral
      cholesteatoma and 25 control subjects with bilateral normal ears were subjected
      to otomicroscopical and audiological assessment. Axial and coronal computed
      tomography (CT) for the mastoid bone at 1 mm slice thickness was done for all
      ears. A simplified method was used to find out the surface area (SA) of the air
      cells at each individual section and semi-automatically calculate the total
      volume of the matstoid air cells. RESULTS: Otomicroscopically, 72% of the
      contralateral ears showed signs of retraction pockets, granulation tissues and
      other signs of chronicity. Audiologically 20% of the control ears showed moderate
      to severe conductive hearing loss while 10% showed mixed hearing loss. As regards
      mastoid pneumatization, the mean air cell volumes were 6.1, 12.68 and 29.92 CC in
      cholesteatomatous, contralateral and control ears respectively. This indicates a
      highly significant difference in the mean air cell volume between the control
      ears and the other two groups. CONCLUSION: It can be concluded that continuous
      follow up of the contralateral ear in cholesteatomatous ears is mandatory to
      detect subtle pathological changes and manage them early. Volumetry of
      contralateral ear using the applied simple method can lead to a reduction in
      major surgery and can affect the choice of the surgical approach.

PMID- 15244025
TI  - [Delayed facial palsy after vestibular schwannoma resection: the role of viral
      reactivation. Our experience in 8 cases].
AB  - OBJECTIVE: To study the role of herpes virus reactivation in the onset of more
      than three days-delayed facial paralysis (FP) following vestibular schwannoma
      (VS) surgery and advocate a specific medical management. MATERIAL AND METHODS:
      Retrospective study on 8 cases from a series of 348 patients operated on of a VS
      between 1996 and 2002. Seven of the eight patients were given intravenously
      acyclovir (30 mg x kg(-1) x d(-1) for 5 days) and methyl-prednisolone (2 mg x kg(
      1) x d(-1) for 7 days). A serologic testing looking for specific anti-herpes
      simplex viruses type 1 and 2 (HSV-2) and varicella-zoster virus (VZV) antibodies
      at the onset of the FP and 2 weeks later could be done in only 3 cases. RESULTS:
      Mean delay of FP onset was 8.75 days. Mean time for recovery with intravenous
      treatment was 90 days. All treated patients had a House and Brackmann grade 1
      recovery. The last one had only a grade 3 after 400 days of evolution: he could
      not be treated because of postoperative transient psychiatric problems. Serologic
      testing revealed in those patients in whom it could be done either a high level
      of anti-HSV or -VZV antibodies at the time of onset or a dramatic increase in
      anti-HSV or anti-VZV antibodies between the two samples, strongly suggesting a
      HSV or VZV reactivation. CONCLUSION: HSV or VZV reactivation can be evocated in
      most cases of delayed FPs arising in the postoperative course of VSs, suggesting
      usefulness of emergency-given steroid and acyclovir intravenous regimen to block
      virus replication and fight secondary oedema and inflammation causative of nerve
      lesions. Evoked reactivation mechanism is comparable to that already suspected in
      delayed FP arising with the same delay in middle ear surgical procedures.

PMID- 15244026
TI  - Bilateral latero-pontine infarction: a rare syndrome, an unusual imaging.
AB  - The authors present one case of bilateral infarction of the brain stem, in the
      territory of the antero-inferior cerebellar artery. Besides the fact that such
      bilateral ischaemic lesions are rare, the initial clinical presentation mimicking
      a vestibular neuronitis indicates that this latero-pontine syndrome may appear as
      a peripheral disorder. It also reminds clinicians that careful and repeated
      examinations should always be performed in all patients suffering from vertigo.
      An unusual iconography is also presented.

PMID- 15244027
TI  - The effect of the speaker gender on speech intelligibility in normal-hearing
      subjects with simulated high frequency hearing loss.
AB  - OBJECTIVE: To determine whether speaker gender affects speech discrimination
      scores, in normal hearing and simulated high frequency hearing loss situations.
      MATERIALS AND METHODS: Listeners were twenty normal volunteers. The speech
      stimuli were eight phonetically balanced monosyllabic word lists, uttered by a
      male and a female speakers. These lists were low-pass filtered at 1500, 2500 and
      3500 Hz's to represent high frequency hearing loss. To obtain speech
      discrimination scores, the subjects listened to each of the eight lists in a
      different filtering and talker conditions in a randomized order. For statistical
      analysis, Mann-Whitney U test was used. RESULTS: In normal hearing situation, the
      scores obtained by male and female speeches, were similar (p=0.60). On the
      contrary, statistically significant differences were observed in all of the three
      high frequency hearing loss situations (p<0.01). CONCLUSION: Female speech is
      significantly more difficult to discriminate than male speech in normal-hearing
      subjects with simulated high frequency hearing loss and probably in patients with
      high frequency hearing loss.

PMID- 15244028
TI  - [Early ENT manifestations of HIV infection/AIDS. An analysis of 76 cases observed
      in Africa].
AB  - OBJECTIVE: The aim of this work is to describe the ENT clinical manifestations by
      which HIV positive patients inaugurate their AIDS-illness and to classify these
      manifestations in respect to the biological state of the infection. MATERIAL AND
      METHOD: It was a multicenter, prospective study carried out in the ENT services
      of Yaounde (Cameroon), between the period of September 2000 and June 2002.
      Included in this study were HIV patients who started their AIDS with an ENT
      illness. The stage of evolution of the HIV infection was evaluated using the CD4
      and CD8 T lymphocyte counts. This was carried out using the Flux cytometric
      technique of Fascount/Becton. RESULTS: We thereafter recruited 76 patients. The
      incidence rate of ENT early manifestations in HIV positive patients was 11.5%.
      Pharyngeal and oral candidosis represented the most observed manifestation
      (30.60%), followed by peripheral facial paralysis (11.13%) and rhino-sinusitis
      (10.58%). Parotid gland hypertrophy represented 8.23% of the affections.
      Persistant cervical lymphadenopathy was observed in 7.05% of cases. Kaposi
      sarcoma and cervical lymph node tuberculosis represented each 3.53% of cases of
      the sample. The correlation of lymphocytic count and initial ENT manifestations
      showed that these manifestations were observed in all the biological states of
      the HIV/AIDS infection. CONCLUSION: The above mentioned ENT manifestations in the
      patient should motivate the request of the HIV screening tests.

PMID- 15244029
TI  - [Adenomatoid hamartoma of the ethmoid sinus: one case report].
AB  - INTRODUCTION: Hamartomas are non-malignant malformations or inborn errors of
      tissue development. In the head and neck region, especially in the nasal cavity
      and the ethmoid sinuses, they are relatively rare. PATIENTS AND METHODS: A case
      of respiratory epithelial adenomatoid hamartoma of the ethmoid sinus and a review
      of literature are reported in order to describe the diagnostic and therapeutic
      management of this tumour. RESULTS: A 74-year-old man complaining for unilateral
      nasal obstruction for years was referred to our institution. Clinical and
      radiological studies revealed a large intra-nasal tumour, osteolytic in nature,
      arising from the right ethmoidal sinus. Fifteen months after a complete excision
      of the tumour using an endoscopic procedure, the nasal cavity was free of tumour.
      DISCUSSION AND CONCLUSION: Very rare and classified as non-malignant tumours,
      hamartomas are composed of excessive proliferation of one or more cellular
      components specific to a given tissue. They can grow out of any part of the body
      for example the surface epithelium, seromucous glands and vessels. Hamartomas
      commonly originate from the lung, kidney and intestine. Their localisation in the
      nasal cavity, especially in the ethmoid sinus, is unusual, but it is really
      important to be known to distinguish hamartomas from papillomas and
      adenocarcinomas not to perform useless and destructive surgery.

PMID- 15244030
TI  - [The infrahyoid musculocutaneous flap: experience of 153 cases in the
      reconstruction of the oropharynx and oral cavity after tumoral excision].
AB  - The infrahyoid musculocutaneous flap was described by Wang in 1986. The authors
      utilize this type of flap since 1994 with an importance that increases in the
      field of head and neck reconstructive surgery. Their experience of 153
      reconstructions in oropharynx and oral cavity showed 128 (84%) cases with good
      cicatrisation and 25 (16%) with complications. In the cases with complications,
      they noted 17 partials necrosis (50% of the skin area), 4 late cicatrisation and
      4 total necrosis. Only the total necrosis necessitated the other new flap. These
      results show that the fiability and function of this flap creates an
      indispensable flap in reconstruction of the oropharynx and oral cavity.

PMID- 15244031
TI  - Schwannoma of the postcricoid region: report of a first case.
AB  - Schwannoma is one of the very rare benign tumours of the hypopharynx. It has to
      be distinguished from malignant tumours arising from this region. We report the
      management of a case of postcricoid schwannoma with a review of the literature.

PMID- 15244032
TI  - [Adult laryngeal cavernous hemangioma: a case report].
AB  - We describe a case of laryngeal venous malformation, discovered by dysphonia.
      This malformation has a different histology and evolution compared to infant
      laryngeal hemangioma. The histological exam shows large and multiple vessels
      lined by regular endothelium. There is no spontaneous regression; this
      malformation can be stable or increase and induce a laryngeal obstruction.
      Although inconstant, a bluish colour, seen at endoscopy, suggests the presence of
      venous malformation. The diagnostic is confirmed by MRI, which shows local
      extension. We propose regular clinical and radiological supervision for
      asymptomatic venous malformations. Treatment is recommended only for symptomatic
      patients usually by laryngeal microsurgery or cervicotomy. Per cutaneous
      sclerosis is an interesting alternative therapy alone or prior to surgery.
      Regular follow-up is essential in order to detect frequent recurrences.

PMID- 15244033
TI  - [Diagnosis management of Warthin tumour: clinical presentation, fine needle
      cytology and MRI].
AB  - OBJECTIVES: Warthin tumour is the second most frequent benign tumour of the
      parotid gland after pleomorphic adenoma. The aim of this retrospective study was
      to define clinical, cytological and MRI characteristics in order to work out a
      therapeutic strategy. MATERIAL AND METHOD: During the period May 1991-January
      2003, 53 patients with Warthin tumors were treated in our institution. Clinical
      data were reported from medical records reviewing. Histological diagnoses were
      compared with FNAB and MRI results. RESULTS: Warthin tumours represented 13% of
      all parotid lesions of our series. Mean age of patients was 58 year-old. Sex
      ratio was 3.8 men and 1 woman. Sensitivity of FNAB for Warthin tumour diagnosis
      was 75% while positive predictive value was 71%. Six cases of false positive
      patients were reported: 2 acinic cells carcinomas, 2 pleomorphic adenomas, 1
      dermoid cyst, 1 branchial cyst. CONCLUSIONS: Surgical management is based on
      partial parotidectomy that may be adapted to the tumour location. Because of
      elderly patients, benign nature and low risk of malignant transformation of
      Warthin tumours, one might prompt to adopt a conservative strategy, avoiding
      surgery in some cases. Despite diagnosis of Whartin tumour on FNAB and MRI, one
      must be cautious in recommending conservative treatment in order to avoid
      ignoring a surgical tumour.

PMID- 15244034
TI  - [Migraine, neurons and vessel].

PMID- 15244035
TI  - Prevention of homocysteine thiolactone induced atherogenesis in rats.
AB  - Thioretinamide was conjugated to coenzyme B12 to produce thioretinaco.
      Thioretinamide, thioretinaco, and coenzyme B12 were injected weekly into Rattus
      rattus that were also given atherogenic doses of homocysteine thiolactone. The
      presence or absence of lesions in aorta-intercostal artery junctions was
      examined. Control rats injected with homocysteine thiolactone (CON-Hcy) had 56.6
      +/- 5.8% lesions when compared to 34.8 +/- 3.4% in control rats injected with
      saline (CON-Sal). Rats that received homocysteine thiolactone injection with
      thioretinamide (NHTR-Hcy), thioretinaco ((NHTR)2B12-Hcy), and coenzyme B12 (B12
      Hcy) had 30.1 +/- 4.2%, 27.5 +/- 3.5%, and 22.8 +/- 3.0% lesions, respectively.
      These lesion rates were not different from those of rats receiving thioretinamide
      (NHTR-Sal), thioretinaco ((NHTR)2B12-Sal), and coenzyme B12 (B12-Sal) which were
      31.3 +/- 1.8%, 29.8 +/- 3.9%, and 32.0 +/- 4.6%, respectively. In this study the
      percentage of intercostal artery lesions in rats receiving thioretinamide and
      homocysteine (NHTR-Hcy), coenzyme B12 and homocysteine (B12-Hcy), and
      thioretinaco and homocysteine ((NHTR)2/B12-Hcy) were significantly lower, 53.2%,
      48.6%, and 40.3% respectively, compared to than that of the control group
      receiving homocysteine (CON-Hcy). Thioretinaco, thioretinamide, and coenzyme B12
      provided protective effects against the atherogen homocysteine thiolactone. A new
      method for the synthesis of the N-substituted derivative of homocysteine
      thiolactone, thioretinamide, was also reported.

PMID- 15244036
TI  - Concentration-dependent preferences of absorptive and excretive transport cause
      atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts
      as an interface between the body and ingested compounds.
AB  - Intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor
      of gliotoxin, was studied in isolated rat small intestine as a model cyclic
      dipeptide. Absorption clearance (CLabs) decreased in the presence of
      glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide
      cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C.
      These indicate that cyclo(Phe-Ser) is in part transported by PEPT1. However,
      Eadie-Hofstee plot of absorption revealed an atypical profile at lower
      concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative
      experiments of absorptive and excretive transport showed that excretive transport
      from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM
      cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the
      serosal side, and vise versa at a 1 mM cyclo(Phe-Ser). These results as well as
      the results of kinetic analysis indicate that intestinal absorption consists of
      passive transport, carrier-mediated absorptive transport by PEPT1 and carrier
      mediated excretive transport, resulting in atypical absorption. Although cyclic
      dipeptides have potentials for drug, their intestinal absorption may be complex.
      The results of this study lead us conclude that absorptive and excretive
      transport by the small intestine acts as an interface between the body and
      ingested compounds.

PMID- 15244037
TI  - Liver L-carnitine biosynthesis in non-pregnant, pregnant and lactating rabbits.
AB  - The present study reports liver carnitine biosynthesis and concentrations in non
      pregnant (dry), pregnant and lactating rabbits (n = 17). To determine carnitine
      biosynthesis in liver tissues; we purified gamma-butyrobetaine hydroxylase, a key
      enzyme in carnitine biosynthesis, and measured its activity. An isocratic high
      performance liquid chromatography (HPLC) method was used to determine L-carnitine
      levels in liver samples. When compared with dry period, during pregnancy, free
      and acid-soluble total carnitine concentrations did not change significantly
      (p>0.05). In contrast to free and acid-soluble total carnitine, short chain
      acylcarnitine concentration increased significantly in the second period of
      pregnancy, compared with non-pregnant rabbits. Highest concentrations of free,
      short-chain acyl- and acid-soluble total carnitine were measured at the 4th day
      of lactation (487 +/- 29; 392 +/- 26 and 879 +/- 38 nmol/g wet weight
      respectively). gamma-Butyrobetaine hydroxylase activity increased with the
      duration of pregnancy and in late pregnancy it increased significantly compared
      to previous periods. Highest activity was measured in early lactation period (361
      +/- 28 pmol carnitine/min/mg protein). We concluded that, biosynthesis of
      carnitine in liver increases gradually in late pregnancy and early lactation in
      rabbit, and this may be regulated by hormonal changes during these periods.

PMID- 15244038
TI  - Pharmacokinetic changes of intravenous 2-(allylthio) pyrazine, a chemoprotective
      agent, in rats with acute renal failure induced by uranyl nitrate.
AB  - It was reported that the total body clearance (CL) of 2-(allylthio)pyrazine (2
      AP) was significantly faster after intravenous administration of 2-AP to rats
      pretreated with 3-methylcholanthrene (an inducer of CYP1A1/2 and 2E1 in rats)
      than that in control rats. It was also found that the CYP2E1 increased 2-4 times
      in rats with acute renal failure induced by uranyl nitrate (U-ARF) compared with
      those in control rats. Therefore, it could be expected that the pharmacokinetics
      of 2-AP could be changed in rats with U-ARF. After intravenous administration of
      2-AP, 50 mg/kg, to rats with U-ARF, the area under the plasma concentration-time
      curve from time zero to time infinity (AUC) of 2-AP was significantly smaller
      (1030 versus 1360 microg min/ml) and this could be due to significantly faster CL
      of 2-AP (48.4 versus 36.8 ml/min/kg). This could be due to increased CYP2E1 in
      rats with U-ARF. More studies are required to find increased metabolite(s) of 2
      AP in rats with U-ARF.

PMID- 15244039
TI  - Pharmacokinetics of tolbutamide after oral administration in rabbits with folate
      induced renal failure.
AB  - The pharmacokinetic changes of tolbutamide were studied after oral administration
      to normal rabbits and mild and medium folate-induced renal failure rabbits.
      Tolbutmide 50 mg/kg was orally administered to the rabbits. The plasma
      concentrations of tolbutamide were significantly increased (p<0.05) at 9 to 24 hr
      in mild and medium folate-induced renal failure rabbits compared with those in
      normal rabbits. Therefore, the area under the plasma concentration-time curves
      (AUC) was significantly higher (p<0.05 and p<0.01 respectively) in mild and
      medium folate-induced renal failure rabbits (2906 microg/ml x hr and 4074
      microg/ml x hr) than that in normal rabbits (2295 microg/ml x hr). The cumulative
      urinary excretion of tolbutamide was significantly decreased (p<0.05) in medium
      folate-induced renal failure rabbits (3.3 mg) compared with the normal rabbits
      (5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly
      slower in medium folate-induced renal failure rabbits (0.027 hr(-1)) than that in
      normal rabbits(0.044 hr(-1)). The terminal half-life of tolbutamide in medium
      folate-induced renal failure rabbits (25.5 hr) was significantly longer (p<0.01)
      than in normal rabbits (15.7 hr). These results could be considered as possibly
      due to inhibited excretion of tolbutamide metabolites or retarded metabolism of
      tolbutamide.

PMID- 15244041
TI  - [Supportive care].

PMID- 15244040
TI  - Surfactant protein A and D (SP-A, AP-D) levels in patients with septic ARDS.
AB  - The levels of surfactant protein-A (SP-A) and surfactant protein-D (SP-D) in the
      serum of patients with septic acute respiratory distress syndrome (ARDS) were
      determined. Patients with sepsis without ARDS were examined as controls. The mean
      serum SP-A level in the former group was 37.6 +/- 16.2 ng/ml and in the latter
      group was 31.8 +/- 9.6 ng/ml. The difference between the two groups was not
      statistically significant. The maximum serum SP-D level was 83.0 +/- 33.9 ng/ml
      in the control group of patients without ARDS, and 476.3 +/- 391.2 ng/ml in the
      patients with ARDS. The level in the latter population was significantly higher
      than that in the former population. No significant correlation was observed
      between the SP-A and SP-D levels. These results suggest that the serum SP-D
      levels may serve as a good diagnostic indicator of ARDS in patients with sepsis.

PMID- 15244042
TI  - [Occlusion of central venous port catheters after simultaneous 24 h infusions of
      5-FU and calcium-folinic acid in patients with gastrointestinal cancer].
AB  - Folinic acid-modulated 5-FU regimens are standard elements in several
      chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative
      treatment of patients with gastrointestinal cancer. When the simultaneous mixed
      infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the
      BfArM in 2002, we introduced this application regimen in the treatment of our
      cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2])
      received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24
      hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600
      mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10
      ml/hour using a 24 h pump. Central venous catheters employed included single
      Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients
      catheter occlusion was noticed after 8-10 weekly applications of the mixed
      infusion. Heparine and subsequently urokinase were not successful in reversing
      the obstruction. All three catheters had to be explanted. Catheter tips in all
      cases showed a yellow cristalline precipitation. The crystallographic analysis
      exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we
      confirmed calcite formation causing catheter occlusion as a frequent complication
      during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic
      acid. This reaction could not be avoided by increasing infusion volume and the
      application flow rate. As a result of our findings, recommending using calcium
      folinic acid mixed with 5-FU has been withdrawn in the meantime.

PMID- 15244043
TI  - [New pharmaceutical and invasive approaches in cancer pain therapy].
AB  - Recent developments of newer opioids are now alternatives to morphine
      hydrochloride. Fentanyl and buprenorphine can be administered as trans dermal
      therapeutic systems. Hydromorphone and oxycodone can be given orally with
      different adverse profiles compared to morphine hydrochloride. Invasive
      therapeutic options should be kept in mind for patients refractory or resistant
      to conventional analgesic approaches. These approaches are presented and
      discussed, especially the neurolytic blockade of the celiac plexus which is
      important in the therapy of visceral pain. Epidural and intrathecal morphine
      administration can be used in the treatment of severe cancer pain.

PMID- 15244044
TI  - [Eating and drinking at the end of life. Nutritional support for cancer patients
      in palliative care].
AB  - Anorexia, malnutrition followed by cachexia is observed in up to 80% of cancer
      patients with advanced stages of their disease, particularly in head and neck
      cancer, gastro-intestinal cancer and lung cancer. Malnutrition is associated with
      an unfavourable prognosis and has been demonstrated to be associated with an
      increased morbidity and an increased readmission rate. Cachexia itself can be the
      primary cause of death in cancer patients. Early intervention and nutritional
      support may be helpful in preventing anorexia and further weight loss. Successful
      approaches in treating anorexia have been undertaken with corticosteroids and
      gestagenes.

PMID- 15244045
TI  - [Current development in the diagnostics and therapy of systemic fungal infections
      in cancer patients].
AB  - Invasive fungal infections are associated with a high morbidity and mortality.
      They are of growing concern and a severe infectious complication in cancer
      patients treated with intensive chemotherapy. Within the last five years
      substantial progress has been demonstrated for non-culture based diagnostics and
      treatment of invasive fungal infections. Recent developments in the epidemiology,
      diagnostics and treatment of fungal infections are reviewed and discussed in the
      context of the current state of art for the management of invasive fungal
      infections in cancer patients.

PMID- 15244046
TI  - [Opportunistic infections after treatment with monoclonal antibodies].
AB  - During recent years the therapeutic indications of monoclonal antibodies are on
      the increase. Most monoclonal antibodies are immunosuppressants. Thus,
      therapeutic successes are accompanied by an increase of serious infections.
      Closest cooperation between the haematologist/oncologist and the infectious
      diseases specialist is a prerequisite for the successful outcome of treatment of
      the individual patient. Rituximab and alemtuzumab especially pave the way for a
      variety of opportunistic infections. Prophylactic drugs directed against
      bacterial infections and invasive fungal infections have not been proven to be
      useful. Although the efficacy of prophylactic cotrimoxazole against Pneumocystis
      carinii pneumonia has not been thoroughly examined in this setting, it is usually
      given at a dose of two double-strength tablets every other day. Whether
      reactivation of herpes simplex and varizella zoster can be influenced
      prophylactically has not been studied in randomised trials. In case of fever and
      detection of cytomegalovirus reactivation preemptive therapy should be given.

PMID- 15244047
TI  - [Vaccination of the immunocompromised host].
AB  - Vaccinations are safe and effective in immunocompromised patients. Apparently
      most vaccines in this patient population are underutilized. General vaccination
      recommendations are expressed for influenza, diphtheria and tetanus.
      Pneumococcal, meningococcal und Haemophilus influenzae B immunizations are
      specially indicated for patients with or developing B-cell-deficiency. Live
      attenuated vaccines are usually contraindicated. The efficacy of the immunization
      and its indication can be additionally measured by antibody response, which is
      usually decreased compared to healthy subjects. Immunocompromised hosts with
      cancer will benefit from consistent immunization practices. Further clinical
      trials are urgently warranted.

PMID- 15244048
TI  - Supportive treatment for anemic cancer patients.
AB  - Anemia in cancer patients is frequent but often underestimated. Anemia affects
      the health-related quality of life and impacts prognosis and outcome of therapy.
      Treatment options include the administration of hematopoietic growth factors and
      red blood cell transfusions. Blood transfusions result in rapid but often
      transient improvement of anemia. Administration of epoetin or darbepoetin alfa
      increases hemoglobin levels, decreases blood transfusions, and improves quality
      of life in patients with cancer. Presently, trials investigate whether treatment
      of anemic cancer patients with erythropoietin impacts on outcome of chemo- and/or
      radiotherapy and on overall survival. Oncologists must be aware of the clinical
      relevance of anemia and offer adequate treatment options to their patients.
      Supportive treatment of anemic cancer patients presenting anemia-related symptoms
      should be performed to reduce symptoms in cancer patients and optimize outcome to
      anticancer therapy.

PMID- 15244049
TI  - [Immunotherapy of malignant diseases--developments and prospects].
AB  - Conventional strategies in cancer management, such as surgery, chemotherapy or
      radiation therapy are effective treatments for most tumors, but often fail in
      achieving complete remission. The reason for this failure is, that single tumor
      cells have already spread to various organs by the time the tumor is diagnosed
      and lead, often years later, to the development of metastases. Therefore it is
      insufficient to treat the tumor solely at its point of origin; tumor
      dissemination should be prevented too. Tumor immunotherapy is one of the
      treatment options that target tumor propagation. In cancer immunotherapy, the
      immune system of the patient is influenced such, that the tumor is recognized and
      attacked by the body's defences. Since these therapies specifically aim at tumor
      cells, they cause fewer adverse events and improve the quality of life of
      patients. This review outlines previous developments in cancer immunotherapies
      with a focus on active immunotherapies and vaccination strategies.

PMID- 15244050
TI  - Tick-borne encephalitis in childhood--consensus 2004.
AB  - Tick-borne encephalitis (TBE) is a communicable disease caused by a flavi-virus,
      ticks being the main vectors. The nervous system is affected, four clinical
      features of different severity are observed: meningitis, meningoencephalitis,
      meningoencephalomyelitis, meningoradiculoneuritis. TBE is a preventable disease,
      which is rapidly becoming a growing public health problem in Europe. So far no
      causal treatment is possible but an efficient, safe vaccination is available.
      During the 6th meeting of the International Scientific Working Group on TBE with
      the main conference issue "Tick-borne encephalitis in childhood" an international
      consensus was achieved. In countries where TBE is endemic--and not prevented by
      immunization--both children and adults are affected. The disease in children is
      generally milder, although severe illness may occur and even lead to permanent
      impairment of the quality of life due to neuropsychological sequelae. Therefore
      immunization should be offered to all children living in or traveling to endemic
      areas.

PMID- 15244051
TI  - Serendipity 1754-2004--and its children.

PMID- 15244052
TI  - Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its
      neurotoxins.
AB  - Until recently, all clostridia producing neurotoxins able to cause paralysis
      symptomatic of botulism were deemed to be Clostridium botulinum. Defining Cl.
      botulinum on the basis of this single phenotypic trait has resulted in the
      species encompassing metabolically very diverse organisms, and four distinct
      phenotypic groups are recognized within this taxon (designated groups I-IV).
      Nucleic acid hybridization and 16S ribosomal RNA sequencing studies have revealed
      the presence of four phylogenetically distinct lineages within the species, which
      correlate with these phenotypic divisions. In addition to marked phenotypic and
      genotypic heterogeneity between groups, the taxonomy of the species is further
      complicated by the existence of strains which are closely related, if not
      genetically identifiable, to members of each Cl. botulinum group, but are non
      toxigenic. Furthermore, strains of species other than Cl. botulinum (viz. Cl.
      baratii, Cl. butyricum) have been found which express botulinum neurotoxin
      (BoNT). Great advances have been made in recent years in elucidating the
      nucleotide sequences of genes encoding the various BoNT antigenic types (A
      through to G). Genealogical trees derived from BoNTs show marked discordance with
      those depicting 'natural' relationships inferred from 16S rRNA and phenotypic
      clusters, and strong evidence exists for BoNT gene transfer between some groups
      of Cl. botulinum (e.g. groups I and II), and with non-botulinum species.
      Botulinum neurotoxin is produced by Cl. botulinum as a non-covalently bound
      progenitor toxin complex of two or more protein components. Information on the
      evolutionary histories of the various non-toxic progenitor proteins is currently
      limited, although there is evidence of gene recombination. In particular, chimera
      like or mosaic non-toxic-non-haemagglutinins (NTNH) genes in group I Cl.
      botulinum have been described, and it is now apparent that the phylogeny of the
      NTNHs is not going to 'mirror' that of botulinal neurotoxins, although their
      genes are physically contiguous. In this article, the current state of knowledge
      of the phylogenetics of the species Cl. botulinum and its neurotoxins is
      reviewed, and a view is presented that a nomenclature based rigidly on BoNT
      production is no longer tenable.

PMID- 15244053
TI  - Acetoin production as an indicator of growth and metabolic inhibition of Listeria
      monocytogenes.
AB  - It has been shown that Listeria monocytogenes produces acetoin from glucose under
      aerobic conditions. A defined medium with glucose as the sole carbon source was
      used in an aerobic shake flask culture to reliably produce acetoin. Acetoin, the
      reactive compound in the Voges-Proskauer test, was assayable in the medium and
      was used to quantify the metabolic response when inhibitors were added to the
      medium. Inhibitors such as lactic, acetic, propionic and benzoic acids were used
      to demonstrate the utility of acetoin production as an indicator of metabolic
      disruption. With increasing levels of inhibitor, the metabolic and growth
      responses were measured by acetoin production and optical density change,
      respectively. Both measurements decreased in a similar manner with increasing
      inhibitor concentrations. The data also showed the apparent mode of action of the
      inhibitors. A bacteriostatic effect was observed for the protonated organic
      acids, acetic (4 mmol l(-1)) and propionic (4 mmol l(-1)), whereas protonated
      lactic (4 mmol l(-1)) and benzoic (0.16 mmol l(-1)) acids gave an irreversible
      (apparent bacteriocidal) effect. Lactic, acetic, and propionic acids showed
      stimulation of metabolic activity at low concentrations, but benzoic did not.
      Acetoin production is a novel method for quantifying and assessing the mode of
      action of inhibitors against L. monocytogenes. This system can be used to screen
      inhibitors for applications in food safety.

PMID- 15244054
TI  - Ecological determinants for germination and growth of some Aspergillus and
      Penicillium spp. from maize grain.
AB  - This study compared the effect of temperature (5-45 degrees C), water
      availability (water activity, aw; 0.995-0.75) and their interactions on the
      temporal rates of germination and mycelial growth of three mycotoxigenic strains
      of Aspergillus ochraceus and one isolate each of A. flavus, A. niger, Penicillium
      aurantiogriseum and P. hordei in vitro on a maize extract medium. Germination was
      very rapid at > 0.90 aw with an almost linear increase with time for all species.
      However, at < 0.90 aw, the germination rates of A. flavus and P. hordei were
      slower. The aw minima for germination were usually lower than for growth and
      varied with temperature. The effect of aw x temperature interactions on the lag
      phases (h), prior to germination, and on the germination rates (h(-1)), were
      predicted for the first time for these fungi using the Gompertz model modified by
      Zwietering. This showed that A. flavus, A. niger and the two Penicillium spp. had
      very short lag times between 0.995-0.95 aw over a wide temperature range. At
      marginal temperatures, these were significantly higher, especially at < 10
      degrees C for Aspergillus spp. and > 30 degrees C for Penicillium spp. There were
      also statistically significant differences between lag phases and germination
      rates for three different isolates of A. ochraceus. The Aspergillus spp. also
      germinated faster than the Penicillium spp. The temperature x aw profiles for
      mycelial growth varied considerably between species, both in terms of rates (mm
      d(-1)) and tolerances. Predictions of the effects of important environmental
      factors such as temperature, aw and their interactions on lag times to
      germination, germination rates and mycelial growth are important in the
      development of hurdle technology approaches to predicting fungal spoilage in
      agricultural and food products.

PMID- 15244055
TI  - The development of random DNA probes specific for Aeromonas salmonicida.
AB  - RAPD-PCR has been used to produce DNA probes for Aeromonas salmonicida. DNA
      hybridization studies showed that RAPD-PCR fragments of the same size did not
      necessarily hybridize to each other and therefore these sequences were not always
      homologous. However, a single RAPD-PCR fragment (designated 15e) was identified
      as being common to Aer. salmonicida. Subsequently, 15e was found to comprise five
      DNA fragments of similar size which differed in their nucleotide sequences. All
      five fragments were evaluated as DNA probes for the specific detection of Aer.
      salmonicida DNA: two hybridized specifically to DNA of all Aer. salmonicida
      isolates tested, including the four current subspecies and atypical isolates; one
      hybridized to subspecies salmonicida, achromogenes and masoucida, but not
      subspecies smithia; one hybridized to subspecies salmonicida and achromogenes,
      but not subspecies masoucida or smithia; and one hybridized to subspecies
      salmonicida, achromogenes and smithia, but not subspecies masoucida. It is
      believed that these fragments could be useful as non-radioactive probes for the
      safe and rapid diagnosis of these fish pathogens.

PMID- 15244056
TI  - The acetylcholinesterase ichthyotoxin is a common component in the extracellular
      products of Vibrionaceae strains.
AB  - In previous work, it was reported that a strain of Aeromonas hydrophila (B32)
      produces the most potent lethal toxin with neurotoxic activity described so far
      for fish. In the present study, the presence and distribution of this
      acetylcholinesterase toxin lethal for fish were determined in extracellular
      products (ECP) of 42 Vibrionaceae strains using both immunological and
      colorimetric methods. This neurotoxin was shown to be present in the majority of
      the ECP from the Aeromonas and Vibrio strains tested and is responsible for the
      specific acetylcholinesterase activity. Also, although the Western blot and
      Ouchterlony techniques are valid as qualitative methods for the detection of this
      toxin, the Western blot procedure was 100-fold more sensitive than the
      Ouchterlony technique.

PMID- 15244057
TI  - Biguanide-induced changes in Acanthamoeba castellanii: an electron microscopic
      study.
AB  - Trophozoites and cysts of Acanthamoeba castellanii were exposed to chlorhexidine
      diacetate (CHA) and polyhexamethylene biguanide (PHMB); changes in cell
      ultrastructure and surface structure were examined by both transmission and
      scanning electron microscopy. PHMB caused a greater degree of structural and
      membrane damage; the cytoplasmic contents were severely depleted and there were
      clusters of densely stained precipitates on the cell surface. Concentrations of
      CHA greater than 100 microg ml(-1) produced shrinkage from the cyst wall. At high
      concentrations, PHMB induced a slight withdrawal of the cytoplasm from the wall
      and, unlike CHA, induced swelling of the cysts. These findings do not define the
      mechanisms of action of CHA and PHMB, but provide evidence that a major target
      site for both agents is the plasma membrane. However, additional intracellular
      damage undoubtedly contributes to the lethal effects. The greater resistance of
      cysts may be associated with reduced biguanide uptake.

PMID- 15244058
TI  - Myxococcus xanthus biomass as biosorbent for lead.
AB  - This paper deals with lead biosorption by Myxococcus xanthus biomass in which dry
      biomass, accumulating up to 1.28 mmol of lead g(-1), is demonstrated to be a more
      efficient biosorbent than wet biomass. Dry biomass biosorption was found to be
      very rapid, reaching equilibrium after 5-10 min. Culture age, the initial lead
      concentration and pH affected this process, but temperature did not. Furthermore,
      by using sodium citrate as a desorbent agent, 92.17% of the biosorbed lead could
      be recovered. It was also established that the biosorbed lead is located on the
      cellular wall and within the characteristic extracellular polysaccharide of this
      micro-organism.

PMID- 15244059
TI  - Effect of probiotic CenBiot on the control of diarrhoea and feed efficiency in
      pigs.
AB  - The production and testing of a probiotic formulated with a strain of Bacillus
      cereus (Probiotic CenBiot) is reported. The strain was grown in fed batch
      fermenters, desiccated, and mixed with cornflour. To test the effect of the
      probiotic in controlling piglet diarrhoea, two groups of sows and their
      respective litters received feed supplemented with probiotic CenBiot or
      Furazolidone; the control group received the same basic feed but not
      supplemented. Probiotic CenBiot was as effective as Furazolidone, reducing the
      prevalence of diarrhoea to half that in the control group. It also significantly
      improved feed conversion, daily weight gain and total weight gain in pigs in the
      nursery phase. Feed conversion ratios of weaned pigs were 1.904, 2.146 and 2.099
      for the groups that received Probiotic CenBiot, a commercial probiotic, and basic
      feed, respectively. In terms of food consumption, the Probiotic CenBiot group
      consumed 12.6% less than the commercial probiotic group, and 10% less than the
      control group, to achieve the same weight.

PMID- 15244060
TI  - Lactobacillus helveticus heterogeneity in natural cheese starters: the diversity
      in phenotypic characteristics.
AB  - The study of wild strains from natural habitats is a useful means of
      understanding better the heterogeneity within a species of biotechnological
      importance, and of obtaining atypical isolates with unknown capabilities. In the
      present research carried out on different Lactobacillus helveticus strains
      isolated from natural cheese starters, it was observed that several
      biotechnologically important characteristics can differ greatly between strains.
      Biotypes were found which differ in terms of fructose, maltose and trehalose
      fermentation, acidifying activity, proteolytic and peptidase activity, and
      antibiotic and lysozyme resistance. The possibility of choosing Lact. heleveticus
      strains with specific biotechnological profiles will influence the quality and
      the variety of dairy products.

PMID- 15244061
TI  - Metabolic properties, stress tolerance and macromolecular profiles of rhizobia
      nodulating Hedysarum coronarium.
AB  - The drought-tolerant legume Hedysarum coronarium is a Mediterranean species
      valued as a forage crop for its high performance in stressful conditions. The
      plant shows peculiar capabilities of nodulating above pH 9 and thriving in highly
      calcareous soils. With the aim of providing an adequate characterization of its
      bacterial symbiotic partner, a study was undertaken, approaching from several
      viewpoints the physiology and structural features of bacteria isolated from
      nodules of H. coronarium. Tests involved trophic capabilities on different carbon
      and nitrogen sources, vitamin requirements, and resistance to factors including
      antibiotics, heavy metals, salinity, pH, and temperature. Enzyme activities,
      including those of cellulase, pectinase, urease, beta-galactosidase, nitrate and
      nitrite reductase, were evaluated. The DNA G + C percentage content was
      determined. Species-specific bacteriophages were isolated and a strain-typing
      grid established. In order to characterize further and fingerprint the different
      Rhizobium 'hedysari' isolates, electrophoretic pattern of proteins, plasmid DNA,
      and digested genomic DNA (in pulsed-field gel separation) were compared.
      Adansonian taxonomy yielded similarity clusters of the different isolates.

PMID- 15244062
TI  - Cell membrane integrity and lysis in Lactococcus lactis: the detection of a
      population of permeable cells in post-logarithmic phase cultures.
AB  - A method was developed that enabled an analysis of the proportion of permeable
      cells in a culture of Lactococcus lactis. This used the fluorescence of propidium
      iodide (PI) when in contact with DNA and the impermeability of the intact cell
      membrane to this compound. A permeability index was suggested that expresses the
      PI-induced fluorescence of a cell suspension as a percentage of the value
      obtained from wholly permeabilized cells after treatment with
      cetyltrimethylammonium bromide. This method was applied to the determination of
      cell permeability in death phase cultures. A large proportion of unlysed cells
      was freely permeable to PI, a finding that may have some significance for the
      investigation of the role of cell lysis in cheese maturation. This method is
      suggested as a useful addition to the techniques available for the study of cell
      damage in a variety of fields, and for the screening of cheese starter bacteria.

PMID- 15244063
TI  - Cultural conditions for the production of bacteriocin by a native isolate of
      Lactobacillus delbruecki ssp. bulgaricus CFR 2028 in milk medium.
AB  - The effect of growth parameters and the molecular basis for antibacterial
      activity by a natural isolate of Lactobacillus delbruecki ssp. bulgaricus CFR
      2028 was studied. The inhibition was tested against a toxigenic strain of
      Bacillus cereus F 4810. When grown in milk medium, the activity was highest at an
      incubation temperature of 37 degrees C in 48 h. The antibacterial activity
      appeared to be produced between late logarithmic and early stationary phases. The
      active principle was proteinaceous in nature (bacteriocin) and stable to low pH
      (3.8-5.0) and heat (75 degrees C for 30 min). There was also the possible role of
      hydrogen peroxide in bringing about inhibition. The strain of Lact. delbruecki
      ssp. bulgaricus CFR 2028 revealed the presence of plasmid DNA bands of 9.4 and
      6.5 kbp, respectively, in agarose gel electrophoresis. The above strain has the
      potential to be used as a biopreservative in popular Indian fermented foods.

PMID- 15244064
TI  - Pulsed-field electrophoretic fingerprinting of Salmonella indiana and its
      epidemiological applicability.
AB  - Eight Xba I-generated pulsed-field profile (PFP) types and four subtypes within
      one of the most common PFP types have been identified in Salmonella indiana from
      patients, poultry and human food in England and Wales in the three-year period
      from January 1994 to December 1996. Two PFP types have predominated, PFP X1 and
      PFP X2. Although the PFP X1 type was identified throughout the study period, the
      PFP X2 type was not identified until late 1995, subsequently becoming the most
      common PFP type in humans in the first six months of 1996 with a significant
      distribution in elderly patients. It is concluded that PFGE can be used in
      support of epidemiological investigations for the subdivision of Salm. indiana.
      Furthermore, as both conditions and interpretation criteria can be easily
      standardized, it is suggested that for many salmonella serotypes, PFGE can
      provide the basis for a definitive scheme of genotypic subtyping suitable for
      epidemiological investigations at both a national and international level.

PMID- 15244065
TI  - Enzymes involved in carbohydrate metabolism and their role on exopolysaccharide
      production in Streptococcus thermophilus.
AB  - The role of the enzymes uridine-5'-diphospho-(UDP) glucose pyrophosphorylase and
      UDP galactose 4-epimerase in exopolysaccharide production of Gal- ropy and non
      ropy strains of Streptococcus thermophilus in a batch culture was investigated.
      Growth of the ropy and non-ropy strains was accompanied by total release of the
      galactose moiety from lactose hydrolysis in modified Bellinker broth with lactose
      as the only carbon source. This was associated with a greater exopolysaccharide
      production by the ropy strain. The polymer produced by both strains in cultures
      with lactose or glucose as carbon sources contained glucose, galactose and
      rhamnose, indicating that glucose was used as a carbon source for bacterial
      growth and for exopolysaccharide formation. UDP-glucose pyrophosphorylase
      activity was associated with polysaccharide production during the first 12 h in a
      20 h culture in the ropy strain, but not in the non-ropy strain. UDP-galactose 4
      epimerase was not associated with exopolysaccharide synthesis in any strain. The
      evidence presented suggests that the glucose moiety from lactose hydrolysis is
      the source of sugar for heteropolysaccharide synthesis, due to a high UDP-glucose
      pyrophosphorylase activity.

PMID- 15244066
TI  - Phenotypic diversity of Xanthomonas sp. mangiferaeindicae.
AB  - Carbohydrate utilization profiles by means of the API (Appareils et Procedes
      d'Identification) system and sensitivity to antibiotics and heavy metal salts of
      68 Xanthomonas sp. mangiferaeindicae strains isolated in nine countries from
      mango (Mangifera indica L.) and other genera of the Anacardiaceae were examined
      to assess the variability of the taxon. The strains could be separated into 10
      groups according to Ward clustering. Apigmented strains isolated from the pepper
      tree [syn. Brazilian pepper] (Schinus terebenthifolius Raddi) could not be
      clearly differentiated from most apigmented strains isolated from mango. Yellow
      pigmented strains isolated from mango in Brazil and Reunion Island, apigmented
      strains isolated from mango in Brazil and from ambarella in the French West
      Indies, clustered in distinct groups. The results are consistent with those of
      other studies, based on isozyme analysis of esterase, phosphoglucomutase and
      superoxide dismutase, and hrp-RFLP analysis; they indicate the need for a
      comprehensive taxonomic evaluation of xanthomonads associated with Anacardiaceae.

PMID- 15244067
TI  - Selection of lactobacilli for chicken probiotic adjuncts.
AB  - During inhibitory activity screening of 296 strains of lactic acid bacteria from
      the gastro-intestinal tract of chicks, 77 strains showed inhibition against
      enteric indicator strains (Salmonella enteritidis and Escherichia coli). Eight
      different strains identified as Lactobacillus salivarius were selected for the
      following attributes: their ability to inhibit all the indicator strains; a high
      adhesion efficiency to the epithelial cells of chickens and also their resistance
      to a number of antibiotics, monensin, bile salts and pH 3.0. The inhibitory
      action was not affected by the addition of catalase and no inhibition was
      detected after neutralizing the supernatant culture fluid. The competitiveness of
      the most promising strains, Lact. salivarius CTC2183 and CTC2197, was assessed in
      chicken feed mixture and in vivo. It was concluded that both strains were capable
      of becoming predominant over the indigenous flora in the incubated chicken feed
      mixture. In vivo tests showed that Lact. salivarius CTC2197 was able to colonize
      and overcome Lact. salivarius CTC2183 and the indigenous flora in the crop and
      caecum of the inoculated chicks.

PMID- 15244068
TI  - A high prevalence of Clostridium botulinum type E in Finnish freshwater and
      Baltic Sea sediment samples.
AB  - The distribution of Clostridium botulinum serotypes A, B, E and F in aquatic
      environments of the Baltic Sea and Finnish mainland was examined. A total of 110
      samples were tested with a neurotoxin-specific PCR assay. Clostridium botulinum
      type E was found in 81% of sea and 61% of freshwater samples. No other
      toxinotypes were found. Spore counts were quantified by the most probable number
      method, Cl. botulinum type E kg(-1) averaging 940 in sea and 370 in freshwater
      samples. The overall prevalence and spore counts of Cl. botulinum type E in
      aquatic sediments correlated significantly with offshore bottom oxygen content,
      depth, and bioturbation activity, whereas there was no correlation with bottom
      water temperature. These findings indicate the possibility of Cl. botulinum type
      E multiplication or at least, suitable conditions for spore survival, in anoxic
      sediments.

PMID- 15244069
TI  - Inactivation of Salmonella typhi by high levels of volatile fatty acids during
      anaerobic digestion.
AB  - Survival of Salmonella typhi was investigated in an anaerobic digester for cattle
      dung with volatile fatty acid (VFA) levels of 5000 mg l(-1) and pH 6.0. The
      organism was added to the digester only once in the first experiment and daily in
      the other. Survival was monitored on alternate days. In the single dose
      experiment, the counts of Salm. typhi declined rapidly and the pathogen was
      completely eliminated within 12 d in the experimental digester (VFA ca 5000 mg l(
      1) and pH 6.0), whereas 26 d were required in the control digester (VFA ca 100 mg
      l(-1) and pH 6.8). T90 values for the experimental and control digesters were
      2.44 d and 4.80 d, respectively. In the daily dose experiment, a four log
      reduction in the pathogen count was observed in the experimental digester, but
      only a two log reduction in the control digester at the end of the experimental
      period. The mean T90 values for the experimental and the control digester were
      4.22 d and 18.63 d, respectively. In both the experiments, statistical analysis
      of the data showed significant differences in the survival pattern of Salm. typhi
      in the two digesters.

PMID- 15244070
TI  - Pitavastatin enhances the anti-fibrogenesis effects of candesartan, an
      angiotensin II receptor blocker, on CCl4-induced liver fibrosis in rats.
AB  - It has been shown that a statin (3-hydroxy-3-methyl-glutaryl coenzyme reductase
      inhibitor) enhances a suppressive effect of angiotensin II type 1 receptor (AT1
      R) blocker (ARB) on injury-induced transforming growth factor (TGF)-beta
      expression in kidneys. We have shown that TGF-beta plays a crucial role in the
      development of liver fibrosis. In this study, we tested whether a combinatory use
      of a statin (pitavastatin) and an ARB (candesartan) may further inhibit liver
      fibrogenesis in carbon tetrachloride (CCl4)-treated rats. Candesartan (8
      mg/kg/day) significantly suppressed injury-induced TGF-beta 1 expression in
      livers, and attenuated fibrogenesis, as evaluated by masson-trichrome staining
      and hydroxyproline content in livers. Pitavastatin (2 mg/kg/day) alone did not
      affect liver fibrogenesis. However, it enhanced significantly the suppressive
      effects of candesartan on TGF-beta 1 expression and fibrogenesis. Although we do
      not know the underlying molecular mechanisms at this moment, these results
      suggest that a combinatory use of a statin and an ARB may confer beneficial
      effects on human liver fibrogenesis.

PMID- 15244071
TI  - Baroreflex control of the heart rate during central hypovolemic stress in young
      and elderly men.
AB  - To test the hypothesis that tolerance to central hypovolemic stress is diminished
      with a reduced sensitivity of cardiac baroreflex in young and old men, twenty
      four healthy elderly male subjects (67.5+/-0.9 yrs) and 24 young male subjects
      (22.4+/-0.4 yrs) underwent a 21 min bout of ramped lower body negative pressure
      (LBNP) (0 to -60 mmHg, 10 mmHg each for 3 min). Heart rate(HR), blood pressure,
      thoracic impedance (Z0) and calf circumference were measured throughout the
      experimental period. The sensitivity (BRS) of arterial baroreflex control of the
      cardiac interval was calculated from spontaneous changes in beat-to-beat arterial
      pressure and the RR interval during the LBNP test. The occurrence of presyncope
      episodes during LBNP was 16.7% in elderly subjects and 37.5% in young subjects.
      The changes of HR, blood pressure, Z0 and calf circumference in the young (Young
      fainter group) and the elderly (Elderly fainter group) subjects who showed
      presyncope during LBNP did not differ from those in the subjects (Young and
      Elderly nonfainter groups) who did not show presyncope. The steady-state HR
      responses to the changes of Z0 during LBNP did not differ among the four groups.
      In young and elderly subjects, the baseline values of BRS in the fainter groups
      tended to be smaller than those in the nonfainter groups, and the difference in
      the young group was significant (P<0.05). No LBNP-related change of BRS was
      observed in elderly subjects, whereas a gradual LBNP-related decrease was
      observed in young subjects. These findings suggest that 1) aging does not
      increase intolerance to central hypovolemic stress induced by a given LBNP, 2)
      the reduced vagal BRS is related partly to low LBNP tolerance in young and
      elderly men.

PMID- 15244072
TI  - Dysfunction of macrophages in metallothionein-knock out mice.
AB  - Metallothionein (MT) is a low molecular weight protein, rich in cystein residues,
      and induced by stimulation with several stresses such as heavy metals, chemical
      agents, oxygen radicals and irradiation. It is involved in metal metabolism,
      detoxification and radical scavenging and also participates in immune responses.
      In this communication, to study the role of MT in immune responses, we analyzed
      immune functions, especially macrophage functions in MT-knock out (MT-KO) mice in
      vitro. When compared with wild type counterpart (MT-WT) mice, macrophages from MT
      KO mice showed a defect of phagocytic and antigen-presenting activity. Cytokine
      productions such as IL-1alpha, IL-6, IL-10 and IL-12 were reduced in macrophages
      from MT-KO mice. Furthermore, the expressions of CD80, CD86 and MHC class II
      molecules were also reduced in macrophages from MT-KO mice. No obvious
      dysfunction was observed in T cells and B cells. These results suggest that MT
      plays an important role in the regulation of immune responses, especially
      macrophage functions.

PMID- 15244074
TI  - [Intermodal timing cues for audio-visual speech recognition].
AB  - The purpose of this study was to investigate the limitations of lip-reading
      advantages for Japanese young adults by desynchronizing visual and auditory
      information in speech. In the experiment, audio-visual speech stimuli were
      presented under the six test conditions: audio-alone, and audio-visually with
      either 0, 60, 120, 240 or 480 ms of audio delay. The stimuli were the video
      recordings of a face of a female Japanese speaking long and short Japanese
      sentences. The intelligibility of the audio-visual stimuli was measured as a
      function of audio delays in sixteen untrained young subjects. Speech
      intelligibility under the audio-delay condition of less than 120 ms was
      significantly better than that under the audio-alone condition. On the other
      hand, the delay of 120 ms corresponded to the mean mora duration measured for the
      audio stimuli. The results implied that audio delays of up to 120 ms would not
      disrupt lip-reading advantage, because visual and auditory information in speech
      seemed to be integrated on a syllabic time scale. Potential applications of this
      research include noisy workplace in which a worker must extract relevant speech
      from all the other competing noises.

PMID- 15244073
TI  - Differences in mental health consultation between male and female workers in the
      health care center of a private enterprise.
AB  - This study attempted to clarify gender differences associated with mental health
      consultations at a health care center (X center) that services 40,638 (34,491 men
      and 6,147 women) workers and is operated by a Japanese company. Data from 940
      subjects (790 men and 150 women) undergoing first-time consultation at the X
      center between April 1996 and March 2001 were collected from the database. After
      matching age (within 3 years) and occupation between the male and female groups
      by pairing, 58 men and 58 women were compared. There was no difference in work
      inefficiency and diagnosis between the two groups, but the referral route of the
      first consultation differed significantly: males were more frequently self
      referred. Fewer female than male patients were found to have work-related
      complaints. With regard to these work-related complaints, inadequate
      relationships, and especially conflicts with superiors, were found to be the most
      frequent cause among patients of both genders, although differences in the
      content of these complaints did exist.

PMID- 15244075
TI  - ['Vegetable wasps and plant worms' and G-protein-coupled receptors].
AB  - Following the discovery of an immunosuppressive substance isolated from one of
      the entomopathogenic fungi 'vegetable wasps and plant worms', FTY720, whose
      immunosuppressive action is more potent than that of cyclosporin, was developed.
      In contrast to classical immunosuppressants such as cyclosporin, FTY720 does not
      affect the growth, maturation and activation of lymphocytes, but causes a
      reduction in the number of circulating lymphocytes as a result of enhanced homing
      of lymphocytes to the secondary lymphoid organs. It has recently been reported
      that FTY720 is phosphorylated in vivo by sphingosine kinase, and the
      phosphorylated FTY720 is a ligand of the receptors of sphingosine 1-phosphate
      (S1P), which are G-protein-coupled receptors. S1P has been recognized most
      prominently as a platelet-derived lipid mediator which regulates several
      functions of endothelial and smooth muscle cells. In addition, recent studies
      have suggested the crucial roles for S1P in immunological, and inflammatory
      modulation.

PMID- 15244076
TI  - [Screening for prostate cancer in Yahata, Kitakyushu].
AB  - A remarkable increase has occurred in the incidence of prostate cancer in many
      countries including Japan. For early detection of prostate cancer, mass screening
      was initiated in many areas in Japan. We began screening for prostate cancer in
      1993 in the Yahata area. Prior to 1996, prostate cancer screening consisted of
      interview, digital rectal examination, measurement of prostate specific antigen
      and transrectal ultrasonography. Since 1997, only an interview and PSA
      measurement has been performed. This screening program is provided free of
      charge. The men who had abnormal findings on the first screening were advised to
      visit an urologist for further examination. Over a period of 10 years, we
      detected prostate cancer in 6 out of 903 men (0.64%). Of those 6 patients, 5 had
      early localized cancer. In conclusion, we feel it is necessary to increase the
      number of subjects and visiting rate to an urologist, and to determine the
      diagnostic strategies including prostate biopsy on the second screening. In
      addition, the effectiveness of screening should be elucidated.

PMID- 15244077
TI  - [One case of Cronkhite-Canada syndrome, in which the course from onset to
      spontaneous curing could be followed].
AB  - The case is a 62 years old male. No polyposis was found by upper gastrointestinal
      endoscopy or barium enema examination performed at the time of cholecystectomy in
      March 1994. Symptoms such as dysgeusia, diarrhea, loss of hair and atrophy of
      nails began to appear from May. Examination of the digestive tract performed in
      October revealed clustered polyposis in the stomach, duodenum, small intestine
      and large intestine. Pathologically, all the polyps were found to be of the
      juvenile type, so a diagnosis of Cronkhite-Canada syndrome (CCS) was made.
      Histologic patterns of rectal polyp after polypectomy showed well differentiated
      adenocarcinoma continuous with the juvenile type polyp. The above-mentioned
      symptoms improved with the clinical course. At present, 6 years after the
      development of the disease, no recurrence of polyposis in the stomach and large
      intestine has been found. Our results suggest that ectodermal changes and lesions
      of the digestive tract in CCS appear and disappear in a short time.

PMID- 15244078
TI  - [Rehabilitation and return-to-work after laryngectomy: the role of industrial
      otolaryngologists].
AB  - Rehabilitation and return-to-work are important problems for laryngectomized
      patients. Here, we report 2 cases of laryngectomized middle-aged men, and discuss
      the role of otolaryngologists from the viewpoint of an industrial physician. The
      first case is a 55-year-old post-office male clerk, who underwent radical and
      reconstructive surgery for hypopharyngeal carcinoma. He started light work
      following 3-month-rest at home after discharge, and fully returned to his
      previous work 3 years later. The second case is a 50-year-old mailman who also
      underwent radical and reconstructive surgery for hypopharyngeal carcinoma. He
      could not return to work because of the recurrence of tumor during
      rehabilitation. In such cases, comprehensive management including medical, mental
      and social supports is essential according to the occupational environment.
      Industrial otolaryngologists should play an important role in rehabilitation and
      return-to-work of laryngectomized patients.

PMID- 15244079
TI  - Taste masking technologies in oral pharmaceuticals: recent developments and
      approaches.
AB  - Taste is one of the most important parameters governing patient compliance.
      Undesirable taste is one of several important formulation problems that are
      encountered with certain drugs. Oral administration of bitter drugs with an
      acceptable degree of palatability is a key issue for health care providers,
      especially for pediatric patients. Several oral pharmaceuticals, numerous food
      and beverage products, and bulking agents have unpleasant, bitter-tasting
      components. So, any pharmaceutical formulation with a pleasing taste would
      definitely be preferred over a competitor's product and would translate into
      better compliance and therapeutic value for the patient and more business and
      profits for the company. The desire of improved palatability in these products
      has prompted the development of numerous formulations with improved performance
      and acceptability. This article reviews the earlier applications and
      methodologies of taste masking and discusses the most recent developments and
      approaches of bitterness reduction and inhibition for oral pharmaceuticals.

PMID- 15244081
TI  - Assessment of degree of disorder (amorphicity) of lyophilized formulations of
      growth hormone using isothermal microcalorimetry.
AB  - When determining the degree of disorder of a lyophilized cake of a protein, it is
      important to use an appropriate analytical technique. Differential scanning
      calorimetry (DSC) and X-ray powder diffraction (XRPD) are the most commonly used
      thermoanalytical techniques for characterizing freeze-dried protein formulations.
      Unfortunately, these methods are unable to detect solid-state disorder at levels
      < 10%. Also, interpretation of DSC results for freeze-dried protein formulations
      can be difficult, as a result of the more complex thermal events occurring with
      this technique. For example, proteins can inhibit the thermally induced
      recrystallization of the lyophilized cake, resulting in potential
      misinterpretation of DSC degree of disorder results. The aim of this
      investigation was to study the use of isothermal microcalorimetry (IMC) in the
      assessment of degree of solid-state disorder (amorphicity) of lyophilized
      formulations of proteins. For this purpose, two formulations of growth hormone
      were prepared by lyophilization. These formulations consisted of the same amounts
      of protein, mannitol, glycine, and phosphate buffer, but differed in the freeze
      drying procedure. After lyophilization, the recrystallization of the samples was
      studied using IMC at 25 degrees C under different relative humidities (58-75%).
      The effect of available surface area was studied by determining the heat of
      recrystallization (Q) of the samples before and after disintegration of the
      cakes. The results showed that, in contrast to DSC, IMC allowed detection of the
      recrystallization event in the formulations. Although both formulations were
      completely disordered and indistinguishable according to XRPD method, IMC
      revealed that formulation B had a different solid-sate structure than formulation
      A. This difference was the result of differences in the freeze-drying parameters,
      demonstrating the importance of choosing appropriate analytical methodology.

PMID- 15244080
TI  - pH dependent uptake of loperamide across the gastrointestinal tract: an in vitro
      study.
AB  - Loperamide is a peripherally acting antidiarrheal opioid with some affinity for P
      glycoprotein (P-gp). One of the main reasons for its lack of central nervous
      system (CNS) activity is a combination first-pass metabolism and P-gp-mediated
      efflux preventing brain penetration. It was assumed that P-gp would also have a
      similar effect at the intestinal tract, limiting loperamide systemic absorption.
      However, previous in vitro studies had not determined loperamide flux using pH
      gradients present in the intestinal tract. Hence, our aim was to determine the
      influence of pH gradient conditions on the gastrointestinal uptake of loperamide,
      including any changes to its P-gp-mediated efflux. METHODS: Cellular uptake and
      transcellular transport were determined after exposure to various concentrations
      of loperamide (2-50 microM) with and without the presence of active efflux
      protein inhibitors. Loperamide was detected at 214 nm using high-performance
      liquid chromatography (HPLC) protocols. RESULTS: Bidirectional transport studies
      of 10 microM loperamide with a pH 6.0/7.4 apical (Ap)-to-basolateral (Bas)
      gradient showed efflux to be 17-fold higher than influx (10 ng/cm2/min Bas-->Ap
      compared to 0.6 for Ap-->Bas). This differential was much greater than when
      examined at pH 7.4/7.4 (only two-fold higher). The potent P-gp inhibitor, PSC
      833, had only a moderate effect at blocking loperamide efflux under pH gradient
      conditions, yet could equilibrate bidirectional transport at pH 7.4. This
      suggested the presence of significant P-gp independent mechanisms, preventing
      loperamide access to the basolateral chamber. Amiloride and 5-(N-ethyl-N
      isopropyl) amiloride had some effect on reducing efflux, hence the Na(+)--H(+)
      antiporter may have some involvement. Accumulation of loperamide into Caco-2
      cells reduced almost 70% at pH 6.0 compared to pH 7.4, yet P-gp was always able
      to approximately double the equilibrium concentration in the cells within a
      defined pH study. This showed that P-gp was not affected by pH conditions.
      CONCLUSIONS: P-gp-mediated efflux of loperamide is supplemented under pH gradient
      conditions. Hence, drugs used to decrease acid secretion in the stomach could
      result in higher plasma loperamide levels based on our in vitro system reflecting
      the in vivo environment. The addition of a P-gp inhibitor could potentially
      further increase the gastrointestinal absorption of loperamide.

PMID- 15244082
TI  - Profile of rhBMP-2 release from collagen minipellet and induction of ectopic bone
      formation.
AB  - For a cylindrical controlled-release formulation using collagen as a carrier,
      called the minipellet (MP), which contains rhBMP-2, the relationship between the
      diameter of MPs and rhBMP-2 release profiles was investigated, and its effect in
      inducing bone formation was evaluated. Samples with three different diameters
      were tested for each of the following formulations: MP without additives, MP with
      10% (w/w) glutamic acid (Glu) and 20% (w/w) alanine (Ala), and MP with 20% (w/w)
      Glu and 20% (w/w) Ala. The results of the in vitro release test and the amount of
      rhBMP-2 remaining in the MPs after subcutaneous implantation into mice were
      compared among different samples. It was found that the addition of Glu
      accelerated release of rhBMP-2 effectively. Release was accelerated as the
      diameter of MP became smaller and the amount of Glu added increased. The amount
      of calcium formed in 3 weeks after subcutaneous implantation into mice was dose
      dependent. The amount of calcium formed per unit rhBMP-2 dose tended to increase
      as the diameter of MP became smaller and the amount of Glu added became greater;
      calcification was thus associated with release rate. These results indicate that
      MPs with smaller diameters induce bone formation more efficiently. For use in the
      treatment of fracture, etc., MP is considered to be a suitable dosage form, which
      can be administered noninvasively.

PMID- 15244083
TI  - Production of Carbopol 974P and Carbopol 971P pellets by extrusion
      spheronization: optimization of the processing parameters and water content.
AB  - Pellets obtained by extrusion-spheronization represent multiparticulate dosage
      forms whose interest in intestinal drug delivery can be potentiated and targeted
      through bioadhesive properties. However, adhesion itself makes the process
      difficult or even impossible. The problem of tackiness encountered with
      bioadhesive wet masses was previously eliminated by the use of electrolytes such
      as CaCl2. This approach is known to reduce the viscosity of polyacrylic acids by
      disturbing the interactions between carboxylate groups on adjacent polymer
      molecules, thereby decreasing their bioadhesive properties. The present study
      aimed at producing pellets containing carbomers without addition of electrolytes
      in order to maintain their bioadhesive potentiality at its maximum. Carbopol 974P
      (10%, 15% and 20%) and Carbopol 971P (10%) were used in combination with Avicel
      PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350,
      700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes)
      and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain
      the highest yield of spherical pellets ranging 710-1000 microm in diameter. For
      pellets containing 10%, 15% Carbopol 974P or 10% Carbopol 971P and 45% water
      content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and
      time led to the highest yields and sphericities, respectively, 72% and 0.91, 67%
      and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol 974P could be
      achieved through the increase of the water content up to 58% and implementation
      of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and
      time. The yield and sphericity were 42% and 0.78 respectively.

PMID- 15244084
TI  - Oral controlled release formulation for highly water-soluble drugs: drug--sodium
      alginate--xanthan gum--zinc acetate matrix.
AB  - An oral controlled release formulation matrix for highly water-soluble drugs was
      designed and developed to achieve a 24-hour release profile. Using ranitidine HCl
      as a model drug, sodium alginate formulation matrices containing xanthan gum or
      zinc acetate or both were investigated. The caplets for these formulations were
      prepared by direct compression and the in vitro release tests were carried out in
      simulated intestinal fluid (SIF, pH 7.5) and simulated gastric fluid (SGF, pH
      1.2). The release of the drug in the sodium alginate formulation containing only
      xanthan gum completed within 12 hours in the SIF, while the drug release in the
      sodium alginate formulation containing only zinc acetate finished almost within 2
      hours in the same medium. Only the sodium alginate formulation containing both
      xanthan gum and zinc acetate achieved a 24-hour release profile, either in the
      SIF or in the pH change medium. In the latter case, the caplet released in the
      SGF for 2 hours was immediately transferred into the SIF to continue the release
      test. The results showed that the presence of both xanthan gum and zinc acetate
      in sodium alginate matrix played a key role in controlling the drug release for
      24 hours. The helical structure and high viscosity of xanthan gum might prevent
      zinc ions from diffusing out of the ranitidine HCl--sodium alginate--xanthan gum-
      zinc acetate matrix so that zinc ions could react with sodium alginate to form
      zinc alginate precipitate with a cross-linking structure. The cross-linking
      structure might control a highly water-soluble drug to release for 24 hours.
      Evaluation of the release data showed the release mechanism for the novel
      formulation might be attributed to the diffusion of the drug.

PMID- 15244085
TI  - Effect of poly (ethylene glycol) molecular weight and microparticle size on oral
      insulin delivery from P(MAA-g-EG) microparticles.
AB  - Five years of successful work in our lab have shown that graft copolymer networks
      of poly(methacrylic acid-g-ethylene) [P(MAA-g-EG)], are very promising candidates
      for oral drug delivery. In an acidic environment, these copolymers form
      interpolymer complexes, protecting the active agent from the harsh environment of
      the gastrointestinal tract. At high pH, these complexes dissociate, causing the
      polymer to swell and release the drug. Films of P(MAA-g-EG) with a monomer ratio
      of 1:1 (MAA:EG) were prepared by free radical solution UV-polymerization, washed
      in order to remove the unreacted monomer, and crushed to form microparticles with
      different particle size distribution. Previous studies in our lab have focused on
      using polymer disks in their swelling studies. The swelling properties of polymer
      disks vs. crushed particles were investigated via equilibrium swelling
      experiments in this study. Another goal in this study is to compare different PEG
      chain length (MW-400 and MW-1000) and different particle size (150-212 microns,
      90-150 microns and 25-90 microns) in their loading and release behavior. After 6
      hours of exposing the polymer with the insulin solution we achieved approximately
      90% of insulin loading.

PMID- 15244086
TI  - The use of near-infrared spectroscopy for the quantitation of a drug in hot-melt
      extruded films.
AB  - The objective of the study was to demonstrate the utility of near-infrared
      spectroscopy (NIRS) for quantitative analysis of a model drug in hot-melt
      extruded film formulations. Polyethylene oxide (PEO) films with clotrimazole (CT)
      as a model drug were prepared by hot-melt extrusion (HME) incorporating drug
      concentrations ranging from 0-20% and analyzed using a Fourier transform near
      infrared (FT-NIR) spectrophotometer in the reflectance mode, High performance
      liquid chromatography (HPLC) was the reference method used for this study. The
      NIR calibration model derived for CT was composed of 21 frequency ranges that
      were correlated to the values quantified using the HPLC reference method. The NIR
      method developed resulted in an assayed CT amount in the film matrix to be within
      3.5% of the quantity determined by the reference method. These studies clearly
      demonstrate that NIRS is a powerful method for the quantitation of active drug
      substances contained in films produced by HME and warrants further investigation.

PMID- 15244087
TI  - Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate
      using X-ray powder diffraction, near-infrared spectroscopy, and differential
      scanning calorimetry.
AB  - Efficient and accurate quantification of low amorphous and crystalline contents
      within pharmaceutical materials still remains a challenging task in the
      pharmaceutical industry. Since X-ray powder diffraction (XRPD) equipment has
      improved in recent years, our aim was 1) to investigate the possibility of
      substantially lowering the detection limits of amorphous or crystalline material
      to about 1% or 0.5% w/w respectively by applying conventional Bragg Brentano
      optics, combined with a fast and simple evaluation technique; 2) to perform these
      measurements within a short time to make it suitable for routine analysis; and 3)
      to subject the same data sets to a partial least squares regression (PLSR) in
      order to investigate whether it is possible to improve accuracy and precision
      compared to the standard integration method. Near-infrared spectroscopy (NIRS)
      and differential scanning calorimetry (DSC) were chosen as reference method. As
      model substance, alpha lactose monohydrate was chosen to create calibration
      curves based on predetermined mixtures of highly crystalline and amorphous
      substance. In contrast to DSC, XRPD and NIRS revealed an excellent linearity,
      precision, and accuracy with the percent of crystalline amount and a
      detectability down to about 0.5% w/w. Chemometric evaluation (partial least
      squares regression) applied to the XRPD data further improved the quality of our
      calibration.

PMID- 15244088
TI  - Development and evaluation of glyburide fast dissolving tablets using solid
      dispersion technique.
AB  - Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of
      variable bioavailability and bio-inequivalence related to its poor water
      solubility. This work investigated the possibility of developing glyburide
      tablets, allowing fast, reproducible, and complete drug dissolution, by using
      drug solid dispersion in polyethylene glycol. Phase-solubility studies were
      performed to investigate the drug-carrier interactions in solution, whereas
      differential scanning calorimetry, X-ray powder diffraction, and infrared
      spectroscopy were used to characterize the solid state of solid dispersions. The
      effects of several variables related to both solid dispersion preparation
      (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol
      molecular weight) and tablet production (direct compression or previous wet
      granulation, tablet hardness, drug, and solid dispersion particle size) on drug
      dissolution behavior were investigated. Tablets obtained by direct compression,
      with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35
      mesh, i.e., 850-500 microm) of micronized glyburide in polyethylene glycol 6000
      prepared by the cofusion method gave the best results, with a 135% increase in
      drug dissolution efficiency at 60 min in comparison with a reference tablet
      formulation containing the pure micronized drug. Moreover, the glyburide
      dissolution profile from the newly developed tablets was clearly better than
      those from various commercial tablets at the same drug dosage.

PMID- 15244089
TI  - Characterization of amphotericin B liposome formulations.
AB  - Liposomes composed of hydrogenated soya phosphatidylcholine (Emulmetik
      950)/cholesterol/charged lipids [dicetyl phosphate (-) or stearylamine (+)] were
      developed. The hydrogenated soya phosphatidylcholine/cholesterol/charged lipid
      liposomes at molar ratios of 1:1:0, 7:2:0, 7:2:1 (-), and 7:2:1 (+), with and
      without the entrapped amphotericin B (0.05 mg AmB/mg lipid), were prepared by a
      chloroform-film method with sonication. The charges of liposomes were
      characterized by a Zeta-Meter. The negative liposomes with and without the
      entrapped AmB showed higher surface charge density than other formulations. The
      size distribution of liposomes determined by standard error of the mean (SEM) was
      in the range of 0.115 to 0.364 microm. The smallest size was observed in the
      negative liposomes with the entrapped drug [7:2:1 (-) AmB]. The lamellarity of
      more than 15 layers was observed by transmission electron microscope (TEM) in the
      neutral liposomes with the entrapped drug [7:2 AmB]. The transition temperature
      and enthalpy of transition (deltaH) were determined by differential scanning
      calorimetry (DSC). Positive liposomes with the entrapped and unentrapped AmB
      demonstrated higher deltaH of the first peak than other formulations, indicating
      higher rigidity of liposomal membrane. The AmB contents in liposomes were
      determined by high-performance liquid chromatography (HPLC) with ultraviolet (UV)
      detection at 382 nm. The percentages of entrapment of AmB in all formulations
      were above 85%. The positive liposome [7:2:1 (+) AmB] formulation, which gave the
      highest thermal stability, was selected for further skin absorption evaluation.

PMID- 15244090
TI  - Release of diltiazem hydrochloride from hydrophilic matrices of polyethylene
      oxide and carbopol.
AB  - The mucoadhesion, swelling, and drug release behavior of polyethylene oxide (PEO)
      and carbopol (CP) matrices were studied using a water soluble model drug
      diltiazem hydrochloride. The mucoadhesive strength of the matrices increased with
      increase in polymer content. The results showed that PEO was more mucoadhesive
      than CP. Mucoadhesion of the tablets was dependent upon the swelling. Swelling
      was ascertained by measuring the axial and radial expansion of matrix tablets
      following exposure to media of physiological ionic strength. There was a marked
      increase in the swelling index of matrices containing high polymer content of PEO
      as compared to CP. Drug release kinetics were found to be closely related to
      dissolution and swelling properties of the matrices. The release was found to be
      non-Fickian with n (release exponent) values ranging from 0.45-0.58. At a
      constant polymer content (15.84% w/w), the main contributing factor for the
      mucoadhesion, swelling, and release was the amount of PEO.

PMID- 15244091
TI  - Patient Safety Alert. Finding root causes without blame helps eliminate errors.

PMID- 15244092
TI  - Avoid disasters during your next JCAHO survey: quality managers share secrets.

PMID- 15244093
TI  - Staff preparation pays off during a JCAHO survey.

PMID- 15244094
TI  - Care program incorporates office-based CM approach.

PMID- 15244095
TI  - Research to separate DP outcome, process goals.

PMID- 15244096
TI  - Is your organization thinking lean?

PMID- 15244097
TI  - Raise the bar for stroke care certification program.

PMID- 15244098
TI  - Serum antibodies to the major proteins found in cow's milk of Iranian patients
      with Type 1 diabetes mellitus.
AB  - The purpose of this study was to assess the humoral immune response to cow's milk
      proteins in Iranian children with Type 1 diabetes mellitus (T1DM). Eighty
      children aged 4-17 yr with T1DM from two centres in Iran (the Iranian Association
      of Diabetes in Tehran and Center for Diabetes Research in Hamedan), 37 apparently
      healthy siblings of diabetic patients (related controls), 82 apparently healthy
      age- and sex- matched controls (unrelated controls), and 32 patients aged 11-15
      yr with auto-immune thyroiditis were examined for specific whole antibodies
      (Igs), IgG, and IgM to the major proteins found in cow's milk or to ovo-albumin
      by enzyme-linked immunosorbent assay (ELISA). A crude extract was made from 2.5%
      fat pasteurized cow's milk. This extract, together with individual commercial
      major proteins of cow's milk, was then used as antigen to evaluate the humoral
      immune response of the subjects to the individual proteins found in cow's milk or
      to cow's milk as a whole. A questionnaire on medical history, duration of
      exclusive and non-exclusive breast-feeding and daily intake of dairy products was
      completed before blood sampling. Diabetic children had significantly higher serum
      levels of Igs, IgG and IgM to the proteins found in cow's milk than unrelated
      healthy controls (p<0.001). Healthy siblings of diabetic patients, compared to
      unrelated controls, had significantly higher levels of serum Igs and IgG to cow's
      milk proteins (p<0.05 and p<0.01, respectively). Serum levels of Igs and IgG to
      the cow's milk proteins showed a significantly negative correlation with duration
      of non-exclusive breast-feeding but positive correlation with daily intake of
      dairy products. These correlations were stronger when calculated just within the
      T1DM group. In this group, serum levels of IgM to cow's milk proteins also showed
      a positive correlation with daily intake of dairy products. Though serum levels
      of IgG to casein were insignificantly higher in diabetic children than in healthy
      controls, there was a significant negative correlation between serum levels of
      IgG to casein and duration of non-exclusive breast-feeding. Again in the T1DM
      group, this correlation was stronger. There was no significant difference in
      serum levels of Igs, IgG or IgM to other major proteins of cow's milk or to ovo
      albumin between groups. It was concluded that though high levels of Igs or IgG
      were found to cow's milk proteins, especially casein, it seems unrelated to the
      early introduction of cow's milk into an infant diet and the onset of T1DM in
      Iranian subjects.

PMID- 15244099
TI  - Effect of continuous subcutaneous insulin infusion vs multiple daily insulin
      injection with glargine as basal insulin: an open parallel long-term study.
AB  - Aim of this 1-yr open parallel study was to evaluate the efficacy of two regimens
      of intensive insulin treatment: continuous s.c. insulin infusion (CSII) and
      multiple daily insulin injection (MDI) treatment with lispro plus glargine in 48
      Type 1 diabetic patients that had been treated with MDI (regular or lispro
      insulin before each meal plus NPH) for at least 1 yr. Twenty-four patients
      treated with CSII, receiving lispro at multiple basal infusion rates plus boluses
      at meal (CSII group), were compared to 24 patients, matched for age, duration of
      diabetes and metabolic control, treated with MDI with lispro at each meal
      combined with glargine (glargine group). In the CSII group, compared to
      traditional MDI treatment, there was a decrease in HbA1c (9.0 +/- 1.3% during
      traditional MDI vs 8.0 +/- 1.0% during CSII, p<0.001), severe hypoglycaemic
      episodes (0.42 vs 0.17 per patient/yr, p<0.05), insulin requirement (48 +/- 11.7
      vs 35.9 +/- 8.5 U/day, p<0.001). In the glargine group, compared to MDI
      traditional treatment, there was a decrease in HbA1c (8.6 +/- 1.1 vs 7.9 +/-
      1.2%, p<0.001) and severe hypoglycaemic episodes (0.46 vs 0.21 per patient/yr,
      p<0.05). No significant difference between the CSII group and the glargine group
      was present in the degree of improvement in HbA1c and severe hypoglycaemic
      episodes. However, in the CSII group there was a significantly greater reduction
      in mean amplitude of glycaemic excursions (MAGE) and insulin requirement than in
      the glargine group. In conclusion, despite a similar improvement in metabolic
      control, CSII improves blood glucose variability when compared to MDI with
      glargine as basal insulin.

PMID- 15244100
TI  - The impairment of renal function is not associated to altered circulating
      vascular endothelial growth factor in patients with Type 2 diabetes and
      hypertension.
AB  - BACKGROUND: Metabolic and haemodynamic factors concur in the development of
      diabetic nephropathy. Moreover, in diabetes, the presence of hypertension may
      accelerate the development of renal damage. Vascular endothelial growth factor
      (VEGF) stimulates microvascular permeability, endothelium-dependent vasodilation
      and angiogenesis and its synthesis is enhanced by hyperglycaemia, advanced
      glycation end-products (AGEs), tissue hypoxia and hypertension. VEGF appears to
      play a central role in mediating diabetic vasculopathy, and although VEGF and its
      receptors are expressed at renal level, its action in renal pathophysiology is
      unknown. The aim of this study was to elucidate whether presence and/or severity
      of renal dysfunction is related to circulating VEGF in patients with Type 2
      diabetes and hypertension. DESIGN AND METHODS: Fifty hypertensive Type 2 diabetic
      patients and 20 non-diabetic patients were included in the study. Renal function
      parameters such as albumin excretion rate (AER), and glomerular filtration rate
      (GFR), and VEGF plasma levels were analysed in all subjects, whereas %HbA1c and
      AGEs levels were evaluated in diabetic patients. RESULTS: GFR was significantly
      decreased in diabetic patients compared with the control subjects (74.36 +/-
      15.95 vs 111.5 +/- 17.0 ml/min, p<0.0001). Three diabetic patients showed AER
      abnormalities (53.8 +/- 2.3 mg/24h). VEGF in diabetic patients was higher than in
      the control group (77.95 +/- 65.98 vs 49.30 +/- 40.8 pg/ml), but not
      significantly. %HbA1c and AGE levels were 6.6 +/- 1.5% and 11.59 +/- 8.09
      UAGE/ml, respectively. No correlation was found between renal function,
      circulating VEGF levels and metabolic control. CONCLUSION: Diabetes, in
      association with hypertension, significantly decreases renal function, but
      circulating VEGF may not reflect its concentration and action at renal level.

PMID- 15244101
TI  - The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2
      diabetes.
AB  - Plasma homocysteine is an established risk factor for vascular disease and
      precursor of the anti-oxidant glutathione. This study was designed to investigate
      the relationship of changes in homocysteine (Hcy) induced by oral folate to
      glutathione and measures of glycaemia and lipid metabolism in Type 2 diabetes
      (T2DM). Twenty-seven patients (26 male, 1 female, aged 48-68 years) with T2DM and
      microalbuminuria were treated with folic acid 10 mg daily for 3 months. During
      the study, diastolic blood pressure (p=0.04), HbA1c (p=0.04), serum triglycerides
      (p=0.04) and serum total/HDL-cholesterol ratio (p=0.004) all increased and serum
      HDL-cholesterol fell (p=0.006). The increased red cell folate correlated with a
      reduction in microalbuminuria (p=0.001). Overall, plasma glutathione increased
      (p=0.016) despite reduction in its precursor Hcy (p<0.001). Change in glutathione
      correlated inversely with change in HbA1c (p<0.02), total cholesterol (p=0.003)
      and triglycerides (p<0.02) and positively with HDL-cholesterol (p=0.033).
      Increase in glutathione correlated with levels of vitamin B6 (p<0.05). Metformin
      treatment protected against the rise in blood pressure (BP) (p=0.02),
      independently of changes in plasma glutathione. In summary, oral folic acid
      supplementation in T2DM reduced plasma Hcy and increased glutathione levels.
      HbA1c, triglycerides and HDL-cholesterol deteriorated during the trial: their
      levels correlated inversely with changes in glutathione. The increase in
      glutathione may depend on an adequate supply of B6, as changes in glutathione
      correlated with vitamin B6 levels. Reduced Hcy and increased glutathione may both
      mediate improvement in vascular function and outcome. Some aspects of the
      response to folate may be different in patients on metformin.

PMID- 15244102
TI  - The effect of 1-yr sibutramine treatment on glucose tolerance, insulin
      sensitivity and serum lipid profiles in obese subjects.
AB  - The treatment of obesity is strongly recommended because many studies have shown
      it to be a strong risk factor for cardiovascular disease. Although diet and
      exercise are valuable in the treatment of obesity, patient compliance is a major
      problem. Recently, several short- and long-term clinical studies have reported
      significant improvements in obesity treatment with sibutramine. This study aimed
      at demonstrating 1-yr outcome of sibutramine treatment on the lipid metabolism
      and glucose tolerance [with oral glucose tolerance test (OGTT)] in obese
      patients. Seventy-two obese subjects (body mass index >30 kg/m2) were given
      sibutramine at a dose of 10 mg/day and a 1200 calorie diet for 12 months. Nine
      patients were withdrawn from the study (5 because of side effects, 2 because of
      ineffective therapy and 2 for unknown reasons). Sixty-three (6 male, 57 female)
      patients completed the study. Clinical and laboratory measurements were performed
      at the beginning, and after 3, 6 and 12 months of treatment. At the end of the
      study, obese subjects had lower body weights, waist-to-hip ratios, serum
      triglyceride levels, and areas under the curve for glucose and insulin (all
      p<0.001). Serum HDL cholesterol levels and the insulin sensitivity index were
      higher after treatment (both p<0.001). Serum total and LDL cholesterol levels did
      not change significantly during the study. Our results indicate that 1-yr
      treatment with sibutramine along with a low-calorie diet in obese patients
      significantly improves glucose tolerance, insulin sensitivity and some lipid
      levels.

PMID- 15244103
TI  - Progression and distribution of plantar pressure in Type 2 diabetic patients.
AB  - The aim of this prospective 4-yr study was to analyse changes in mean plantar
      pressure (PP) over time and local shifts of maximal PP in Type 2 diabetic
      patients. One-hundred fifty-five Type 2 diabetic patients (age 58.9 +/- 7.5 yr,
      diabetes duration 11.0 +/- 7.6 yr, baseline HbA1c 9.6 +/- 1.6%) were examined
      with regard to foot abnormalities, neuropathy and measurement of PP during
      walking (pedobarography). They were assigned to two subgroups, namely normal PP
      (n=94) and elevated PP (n=57). Patients with an abnormal mean PP did not
      significantly differ from subjects with a normal PP with regard to sex, age,
      duration of diabetes and HbA1c. With the exception of the hallux, the mean PP was
      significantly increased in both groups at all other plantar sites. Maximum PP was
      located below the metatarsal heads (MTH) 2-5 and significantly increased from
      baseline (median, lower/upper quartile: 475, 355/715 kPa) to the end of the study
      (540, 435/749; p<0.0001). On the other hand, PP was normalized in 17 subjects
      (29.8%) who had an elevated PP at baseline. Furthermore, we observed a local
      shift in maximal PP towards the MTH 2-5 region. The percentage of patients who
      had their highest PP under MTH 2-5 was increased from 54.0% at baseline to 61.1%
      at the end of the study. In general, we registered an elevation of PP over time
      and a centralization towards sites which are generally prone to ulceration.

PMID- 15244104
TI  - Nutritional, glycometabolic and genetic factors affecting menarcheal age in
      cystic fibrosis.
AB  - Aims of this study were to investigate menarcheal age (MA) and menarcheal
      determinants in 25 girls with cystic fibrosis (CF) and to compare their MA with
      their respective mothers'. Patients' MA (13.3 +/- 1.1 yr) was on average
      significantly higher (p<0.0005) than that of the respective mothers (12.2 +/- 1.0
      yr) and positively related to it (r=0.055, p<0.005). Six girls experienced
      menarche after 14.2 yr, ie after the uppest limit of their mothers' MA range. The
      only parameter which significantly differentiated these 6 patients from the
      remaining 19 cases was body mass percentile (BMP). Moreover, in the entire
      patient series a negative correlation was found between MA and BMP. None of the
      other clinical parameters correlated significantly with MA. No differences in
      terms of MA were detected in the subgroups of patients with a different glucose
      tolerance (GT) status and the 12 girls with a pathological GT were not older at
      menarche than those with normal GT. No correlations were found between either
      glucose or insulin areas during oral GT test and MA. In the subgroups of patients
      with a different genotype menarche occurred at a similar age, irrespectively of
      their genotype. On the basis of our findings we conclude that: a) a menarcheal
      delay of approximately 1 yr exists between CF girls and their mothers; b)
      menarcheal delay in CF is not related to either genotype or disease severity or
      glycometabolic status; c) the only two factors which are able to affect MA in CF
      are maternal MA and nutritional status.

PMID- 15244105
TI  - Characteristics of Type 2 diabetic patients cared for by general practitioners
      either with medical nutrition therapy alone or with hypoglycaemic drugs.
AB  - The essential role of medical nutrition therapy (MNT) for people with diabetes is
      widely recognised, and its exclusive use is recommended in mild diabetes
      according to a stepwise therapeutic approach. We describe the characteristics of
      MNT-treated Type 2 diabetic patients (vs drugs) cared for by general
      practitioners (GPs) in order to check that appropriate differences did exist
      between the two groups, by auditing the data from our local shared-care program
      for diabetes. We had 16,000 diabetic patients (out of 630,000 inhabitants); 6,800
      of them (42.5%) cared for by GPs. Thirty-one percent (2,079 out of 6,800 patients
      cared for by GPs) were treated with MNT and 69% with drugs. The MNT-treated
      patients (vs drugs) were younger (66.1 +/- 10.7 vs 67.7 +/- 11.0 yr, p<0.01), had
      shorter disease duration (8.2 +/- 6.6 vs 11.2 +/- 7.6 yr, p<0.01), lower HbA1c
      (7.0 +/- 1.1 vs 7.8 +/- 1.6%, p<0.01) and body mass index (BMI) (28.6 +/- 4.6 vs
      29.0 +/- 4.9 kg/m2, p<0.01). They had less prevalence of high blood triglycerides
      (25.4% vs 29.0%, p<0.01). MNT-treated patients had less micro-albuminuria (5.3%
      vs 8.8%, p<0.01); less retinopathy both non-proliferant (6.5% vs 11.1%, p<0.01),
      and pre-proliferant (6.8% vs 12.7%, p<0.01), and proliferant (7.0% vs 12.9%,
      p<0.01); less peripheral neuropathy (3.9% vs 8.3%, p<0.01); and diabetic foot
      (1.0% vs 2.0%, p<0.01). They had less chronic heart failure (2.7% vs 4.6%,
      p<0.01), and claudicatio intermittens (3.3% vs 5.3%, p<0.01). In conclusion, the
      Type 2 diabetic patients cared for by GPs using MNT appropriately had a less
      severe form of diabetes.

PMID- 15244106
TI  - Short-term effects after a 3-month aerobic or anaerobic exercise programme in
      Hong Kong Chinese.
AB  - Information on the beneficial effects of exercise in Chinese concerning weight
      reduction and fat loss is limited. We studied 18 young, healthy Chinese
      volunteers and assessed the short-term effects of exercise on their
      anthropometric and biochemical parameters. They had not done regular exercise
      before the study and were randomly assigned to aerobic or anaerobic exercise
      group (9 subjects in each group). Professional trainers on aerobic and anaerobic
      exercise were invited to teach and supervise the whole group on the exercise
      programme. The study lasted 3 months with exercise of at least 3 sessions per
      week of 30 min each. Of the 18 subjects, 7 (38.9%) were men and 11 (61.1%) women.
      Their mean age was 28.9 +/- 3.6 yr (men: 29.6 +/- 4.2 yr, women: 28.5 +/- 3.4 yr,
      p value: NS). After the 3-month exercise programme, body weight and body mass
      index reduction were significant only in the aerobic group but not in the
      anaerobic one, while body fat percentage was improved in both groups. This
      suggests anaerobic exercise may increase the lean to fat body mass ratio. Plasma
      glucose was reduced in the aerobic group but not in the anaerobic one. Plasma
      insulin level was, otherwise, similar before and after exercise in both groups.
      This is compatible with a blunted insulin hormonal response to endurance exercise
      and an improved tissue sensitivity to insulin.

PMID- 15244107
TI  - [Study of the effect of Stressen on homocysteine blood levels in patients
      affected by vascular disease].
AB  - OBJECTIVE: This study was carried out to confirm the results obtained in a
      previous trial, where Stressen had reduced homocysteinemia in patients with
      elevated concentrations of this amino acid and affected by vascular disease.
      MATERIALS AND METHODS: 50 patients were enrolled and they received Stressen twice
      daily for 30 days. Basal levels of homocysteinemia were determined and, after the
      treatment, evaluation of this parameter was repeated. RESULTS: At enrollment
      homocysteinemia was 23.44 +/- 7.24 micromol/l; at the end of the treatment with
      Stressen it was reduced to 10.22 +/- 3.41 micromol/l, corresponding to a decrease
      of 56.4% (p<0.0001). No significant difference between sexes was noted.
      CONCLUSIONS: The results of this study confirm the efficacy of Stressen on
      homocysteine plasma levels and agree with literature about the relationship among
      vitamin B12, folate and homocysteine; the activity of the drug was therefore
      predictable considering its composition, constituted of cobamamide, calcium
      folinate and arginine glutamate.

PMID- 15244108
TI  - [Effect of Stressen on homocysteine blood levels in patients with cardiovascular
      disease or at risk by familial anamnesis].
AB  - OBJECTIVE: Moderate hyperhomocysteinemia, important risk factor for
      cardiovascular disease, produces an endothelial damage due to oxidative stress;
      high plasma levels of homocysteine can be related either to genetic aberrations
      or to reduced blood concentrations of folate and vitamin B12. The aim of this
      study is to evaluate the effect of Stressen on blood levels of this amino acid in
      patients affected by cardiovascular disease or in healthy hyperhomocysteinemic
      subjects, considered at risk of coronary diseases, due to familiar anamnesis.
      MATERIALS AND METHODS: Homocysteinemia was evaluated by means of an
      immunoenzymatic method in 26 subjects with basal values > 15 micromol/l and
      treated with Stressen, a 10 ml bottle twice daily. RESULTS: After 30 days of drug
      consumption, mean value of total homocysteinemia was 11.6 +/- 1.86 micromol/l,
      corresponding to a statistically significant mean reduction of 42.8% of basal
      values. CONCLUSIONS: Stressen significantly decreased total homocysteinemia in
      this studied population, showing to be suitable for prevention of cardiovascular
      and thromboembolic diseases.

PMID- 15244110
TI  - [The association of lung cancer with asbestos and tobacco smoking].
AB  - This work summarises the potential association link for lung cancer between
      asbestos and smoking. This link emerges not only from different epidemiological
      and experimental studies, but also from a wide data collection carried out by an
      omogeneous Italian industrial group. The examination of the data set has led to
      the conclusion that the simultaneous exposition to asbestos and tobacco's smoke
      entails a factor, usually multiplicative and also partially additive, in relation
      to lung cancer; on the other hand, it does not seem to have a great relevance for
      mesothelioma pleurico. On the basis of this evidence, the Authors focus in
      particular on the measures of prevention in the contest of work conditions, in
      order to highlight the impact of the two carcinogenic agents in workers.

PMID- 15244109
TI  - [Controlled study of the effect of Stressen on homocysteine blood levels in
      patients with vascular disease].
AB  - OBJECTIVE: Plasma levels of folate and vitamin B12 are inversely related to
      homocysteinemia and nowadays a further supplement of these vitamins, other than
      diet, is considered useful for lowering homocysteine blood levels. Stressen
      possesses the requirements for the control of this biochemical parameter; this
      study had the purpose to verify the activity of the product in patients affected
      by vascular disease. MATERIALS AND METHODS: 40 patients have taken a bottle of
      Stressen twice daily for 30 days and 20 subjects, suffering from the same
      pathology and non treated with the drug, have been considered as controls.
      Homocysteinemia was evaluated at the beginning and at the end of the treatment.
      RESULTS: Stressen determined a statistical reduction of 51.1% of basal
      concentration (p<0.0001), while levels of controls remained unchanged after the
      30 days period. CONCLUSIONS: Supplement of vitamin B12 and folate, consisting in
      Stressen administration, normalized homocysteinemia. Furthermore, arginine
      glutamate, in the composition of the product, represents substrate for NO
      synthase and could be particularly useful for the treatment of vascular disease,
      improving endothelial-dependent dilation.

PMID- 15244111
TI  - [Neuroprotective effects of topiramate].
AB  - Topiramate (TPM) is a new anti-convulsant drug, prescribed in epileptic seizure.
      Pharmacological actions of TPM are: a) a positive modulation of GABA receptors;
      b) inhibition of the kainite and aminohydroxymethylisoxazole propionic acid
      (AMPA) glutamate receptor sub-types; c) a use-dependent Na+ channel blocker.
      Recent studies suggest that TPM can have anti-excitotoxic properties, because it
      protects against motor neuron degeneration. Moreover, TPM enhances
      neuroprotection and reduces hemorrhagic incidence in focal cerebral ischemia.

PMID- 15244112
TI  - Antiepileptic drugs in migraine prophylaxis: state of the art.
AB  - Antiepileptic drugs have proven their efficacy in the prophylactic treatment of
      migraine. Our study comprises a clinical trial that examines the efficacy of
      gabapentin and topiramate and a description of the pharmacologic characteristics
      and the efficacy of tiagabine, lamotrigine, levetiracetam and zonisamide.
      Antiepileptic drugs have multiple modes of action which can explain their
      efficacy in reducing neuronal excitability which is proven in epilepsy and
      postulated in migraine. The relationship between epilepsy and migraine has, in
      fact, been much debated but never convincingly proven. Antiepileptic drugs could
      be useful in migraine prophylaxis as some of these have determined a reduction in
      the monthly frequency and intensity of crises in subjects suffering from migraine
      with and without aura. These are the aims that have been proposed by the U.S.
      Headache Consortium Evidence-Based Guidelines. Further double-blind placebo
      controlled studies are necessary in order to assess their safety and efficacy.

PMID- 15244113
TI  - [The right to be born and the need to be born healthy... questions in medical
      ethics].
AB  - INTRODUCTION: Science, thanks to the commitment of huge amount of human capitals,
      in many cases supported even by enormous fund investment, gain continuously
      ground reaching new position and spreading out the borders on human chances in a
      sphere so delicate like birth. New genetic screening tests, new contraceptive
      drugs using even more sophisticated features, comply with the new law on assisted
      insemination, put up new challenges involving all the scientific-social
      environments and necessitate precise answers on ethical side, but even concrete
      commitment on vocational training. PROBLEM: In this case we take working examples
      distinguished only on perception, as the pre-implant diagnosis, the morning after
      pill, and certain about the recent legislation on assisted insemination, to
      highlight their common scientific and cultural milieu. These problems call for an
      unquestionable and unique response, to restore clarity about choices involving
      the need and ability on human being to look for and find answers about
      existential matter as the beginning of life. Human being value and its
      significance need to be relentlessly restated, just because they are endlessly
      debated by a synergy of the emotional point of view, even impressive, and new
      stand out techniques. PROPOSAL: in that sense vocational training is undeniable
      goal, even more, but not only, in a Faculty of Medicine. A student needs to learn
      to reflect on the relations between scientific forthcoming and their ethical and
      bioethical repercussion.

PMID- 15244114
TI  - [Peripheral facial palsy in middle ear surgery: case report and review of
      literature].
AB  - We present a case of a patient who experienced right facial palsy after being
      operated for otosclerosis. Seventeen years before our patient had yet undergone
      the same operation on the contralateral ear and had presented a facial palsy. We
      also report another case of facial palsy and middle ear damage after an operation
      for otosclerosis. Facial palsy is a rare complication of middle ear surgery. It
      is probably caused by a viral relapse and it recedes after few weeks if a proper
      therapy is administrated to the patient. Thus we deem it is useless to perform
      immediately advanced, invasive and expensive tests. On the contrary we believe
      that it is useful, in those cases in which an otosclerotic patient has a history
      of herpes simplex virus infection, to administer a preventive antiviral therapy
      before the operation.

PMID- 15244115
TI  - [Solitary thyroid nodule].

PMID- 15244116
TI  - [Acathisia].

PMID- 15244117
TI  - Promoting physical activity in primary care: how to get over the hurdles?

PMID- 15244118
TI  - Accuracy of the clinical diagnosis of Down syndrome.
AB  - OBJECTIVES: To determine the accuracy of clinical diagnosis of Down syndrome,
      identify problems in reaching a diagnosis, to provide recommendations for
      improvement and estimate a minimum prevalence for all types of Down syndrome.
      DESIGN: A retrospective observational study was carried out over a five-year
      period. Genesis, a database located in the Department of Medical genetics, was
      used to identify the number of Down syndrome karyotypes including trisomy,
      translocation, and mosaic sample variants. Age of diagnosis was determined using
      date of receipt. Karyotyping requests for a clinical diagnosis of Down syndrome
      were also identified. Patient notes and cytogenetic laboratory reports were used
      to identify clinical indication for karyotyping. SETTING: Regional Genetics
      Centre, covering all cytogenetic analyses for referrals within the entire
      Northern Ireland population. RESULTS: 208 postnatal cases of Down syndrome were
      identified, 197 (94.7%) trisomy, 3 (1.45%) translocation, and 8 (3.85%) mosaic
      variants. 112 (54.8%) were male and 96 (46.2%) female. 268 samples were taken to
      confirm or exclude a clinical diagnosis of Down syndrome. 185 of these had Down
      syndrome, 77 were normal, and 6 had another abnormality. 90% and 100% of trisomy
      and translocation Down syndrome respectively were diagnosed on the basis of
      clinical features. This fell to 37.5% of mosaic Down syndrome patients being
      diagnosed clinically (p < 0.001). Simian crease, sandal gap, epicanthic folds,
      hypotonia, upslanting palpebral fissures, and protruding tongue are the most
      frequent characteristic features seen. Similarly epicanthic folds, protruding
      tongue, simian crease and sandal gap, hypotonia, and upslanting palpebral
      fissures are also described in a significant proportion of karyotypically normal
      individuals, thus arousing a suspicion of Down syndrome. 89.4% of patients were
      diagnosed between day 1 and 7 of life. Of 10.6% patients diagnosed after day 7 of
      life, 7.6% were adults and 3% children. The minimum prevalence was estimated at
      167.9 per 100,000, or 1 in 595 births. CONCLUSION: In a defined population, with
      a prevalence of around 1 in 600 births, accurate clinical diagnosis occurred in
      90%, 100%, and 37.5% of trisomy, translocation, and mosaic patients. 49.5% of
      patients had one or more of the following phenotypic findings: Simian crease,
      sandal gap, epicanthic folds, hypotonia, upslanting palpebral fissures, and
      protruding tongue. However, the same six features aroused a suspicion of Down
      syndrome in individuals with normal karyotyping, thus causing undue stress and
      worry to parents. Mosaic cases may be more common than previously recognised, and
      often do not have dysmorphic features. It is therefore a diagnosis that should
      always be considered in those who are educationally subnormal without a
      definitive diagnosis.

PMID- 15244119
TI  - Teaching PRHO prescribing.
AB  - Changes have occurred recently in the teaching syllabus in medical schools across
      the United Kingdom. These changes have taken the format of modular teaching with
      group participation and the grouping of topics such as anatomy, physiology and
      clinical medicine being combined. A short study was designed to assess if
      students of the new curriculum were competent at answering clinical questions
      that occur frequently, and common prescribing requests.

PMID- 15244120
TI  - Requests for emergency contraception at an accident and emergency department-
      assessing the impact of a change in legislation.
AB  - The aim of this study was to examine the pattern of attendance of patients
      requesting Emergency Hormonal Contraception (EHC) at an accident and emergency
      department before and after a government driven change in legislation, which
      allowed EHC to be sold over-the-counter by trained pharmacists, to women aged 16
      years and above. We employed retrospective comparative study using computer
      records of all accident and emergency attendances coded as requests for emergency
      contraception for the years 2000 and 2001. The number of patients requesting
      emergency contraception at the A&E department decreased after over-the-counter
      sales were introduced, from 196 in the year 2000 to 164 in 2001 (p = 0.037).
      Despite this, the number of teenagers requesting emergency contraception at the
      A&E department increased in 2001--from 63 in 2000 to 74 in 2001 (p = 0.0115).
      Most requests are received outside local pharmacy opening hours--63.77% in 2000
      and 62.2% in 2001. This study raises concerns that the government initiative
      allowing emergency hormonal contraception to be sold in pharmacies is having
      little impact on teenagers most in need of this service. A&E departments can
      expect to continue to receive a significant number of requests for emergency
      contraception. Further measures will be required to reduce the U.K.'s high rate
      of unplanned pregnancies.

PMID- 15244121
TI  - MR staging in carcinoma of the endometrium and carcinoma of the cervix.
AB  - This study aimed to evaluate MR as an imaging modality for the assessment of
      myometrial and cervical invasion in endometrial carcinoma and for the assessment
      of parametrial and lymph node involvement in cervical carcinoma. Twenty-eight
      patients with a preoperative histological diagnosis of endometrial
      carcinoma/cervical carcinoma were included in the study. The findings were
      compared with the surgical staging and the histopathological report of the
      hysterectomy specimen. Accuracy in detecting myometrial and cervical involvement
      in patients with endometrial carcinoma was 78% for both. Accuracy in detecting
      parametrial and lymph node involvement in patients with cervical carcinoma was
      71% and 86% respectively. MR is a reliable method for preoperative assessment of
      endometrial and cervical carcinoma. It helps decide operability, the type of
      operation and aids in the selection of patients who need to be considered for
      specialist referral to a gynaecologist oncologist.

PMID- 15244123
TI  - CT-guided fine-needle aspiration of lung nodules: effect on outcome of using
      coaxial technique and immediate cytological evaluation.
AB  - PURPOSE: To evaluate the risk of pneumothorax during CT-guided fine-needle
      aspiration (FNA) of lung nodules with single needle and coaxial needle techniques
      and to assess the effect on diagnostic accuracy of immediate cytological
      examination of lung FNA samples. MATERIALS AND METHODS: This prospective study
      analysed 53 patients undergoing transthoracic FNA biopsy of lung. 36 cases were
      performed by a radiologist using a coaxial technique, with 17 cases performed by
      a radiologist using a direct single-needle method. Effect of technique on
      occurrence of pneumothorax was recorded. FNA samples from all the patients in the
      study were examined immediately on-site by a cytologist or MLSO to determine
      whether sufficient aspirate had been obtained. Provisional diagnosis at immediate
      examination was compared to final diagnosis following full pathological
      evaluation. RESULTS: Coaxial and non-coaxial groups were comparable for age and
      gender. Number of pleural passes was significantly lower in coaxial group (P <
      0.01). Pneumothorax occurred in six (17%) of the 36 patients biopsied by coaxial
      technique, compared to four (24%) of the 17 patients by non-coaxial method (P =
      0.55). Chest tube placement was required in four patients (11%) in the coaxial
      group, and two patients (12%) in the non-coaxial group (P = 0.85). A provisional
      cytological diagnosis was recorded for 74% of the patients in the study. 83% of
      the provisional reports were accurate on comparison with full pathology report.
      Specimen size was sufficient in 81% of cases. CONCLUSIONS: The use of coaxial
      technique for CT-guided lung FNA biopsy reduced the number of pleural passes but
      did not significantly reduce the occurrence of pneumothorax. Immediate
      cytological examination of FNA specimens provided an accurate provisional
      diagnosis in the majority of cases, and should be routinely employed.

PMID- 15244122
TI  - Early experience with chronic hepatitis C in Northern Ireland: epidemiology and
      response to monotherapy.
AB  - Chronic hepatitis C virus (HCV) infection has become a major health problem
      affecting an estimated 170 million people worldwide. The epidemiology of HCV and
      its response to treatment in Northern Ireland has not been described before. Our
      aims were to determine the epidemiology, histological stage, suitability for
      treatment and response to treatment in patients with hepatitis C presenting to
      one clinic in Northern Ireland. All patients were prospectively recruited with
      hepatitis C attending the Liver Clinic, Royal Victoria Hospital during the period
      December 1992 to June 1997. Sixty patients (33 male, mean age 44 years, range 19
      84 years) who tested anti-HCV antibody positive were identified. The predominant
      genotypes were 1b (33%), 3a (28%) and 1a (26%). Most patients (78%) were
      asymptomatic at the time of detection and only four (7%) gave a history of
      jaundice. The most common modes of transmission were i.v. drug use in 30 (50%)
      and blood products in 20 (33%) patients. Forty-eight (86%) of the 56 patients
      tested were PCR positive for HCV RNA. Fifty-one patients (85%) underwent liver
      biopsy of whom 13 had cirrhosis (22% of original group). Twenty-nine patients
      were suitable for treatment, but three declined treatment and only 26 (43%)
      started interferon-alpha. During treatment 17 (65%) patients became PCR negative
      and eight (31%) remained PCR negative 12 months after completion of therapy.
      Liver histology was assessed before and after interferon treatment in 17 patients
      and showed no change in total necroinflammatory scores (p = 0.1) or staging of
      architectural change (p = 0.55). CONCLUSIONS: The epidemiology and response to
      therapy of HCV in Northern Ireland appear comparable to elsewhere in the UK. Only
      a minority of anti-HCV positive non-haemophiliac patients progress to have
      interferon therapy suggesting that the cost of treating chronic HCV may not be as
      great as initially thought.

PMID- 15244124
TI  - Consent to medical treatment--does doctor know best?

PMID- 15244125
TI  - Effort-induced thrombosis of the subclavian vein--a case of Paget-Schroetter
      syndrome.

PMID- 15244126
TI  - Elevated serum beta-hCG due to a tumour of unknown origin.

PMID- 15244127
TI  - Crutch induced axillary artery injury.

PMID- 15244128
TI  - Spontaneous rupture of kidney with peri-renal haematoma: a conservative approach.

PMID- 15244129
TI  - Cervical osteophyte causing perforation of the nasopharynx.

PMID- 15244130
TI  - Carcinoid tumour of the extrahepatic bile duct--report of a case and literature
      review.

PMID- 15244131
TI  - Diclofenac suppositories and acute ischaemic proctitis.

PMID- 15244132
TI  - Can transdermal nicotine patch cause acute intoxication in a child? A case report
      and review of literature.

PMID- 15244133
TI  - Morphology of the functionally univentricular heart.

PMID- 15244134
TI  - Hypoplasia of the left heart.

PMID- 15244135
TI  - Neonatal hemodynamics in patients with hypoplastic left heart syndrome.

PMID- 15244136
TI  - Assessment of the tricuspid valve in hypoplastic left heart syndrome.

PMID- 15244137
TI  - The Norwood procedure for hypoplastic left heart syndrome.

PMID- 15244138
TI  - A European perspective on the management of hypoplastic left heart syndrome.

PMID- 15244139
TI  - Recent innovations in the Norwood sequence of operations.

PMID- 15244140
TI  - Neonatal physiology of the functionally univentricular heart.
AB  - The neonate with functionally univentricular physiology presents unique
      challenges to the cardiac team. An integrated approach that applies working
      knowledge of cardiac anatomy, cardiopulmonary physiology, and basic principles of
      intensive care is essential to guide management of each individual patient. This
      requires cooperative and constructive involvement of a surgical, medical, nursing
      and respiratory care team experienced in the management of such patients. In the
      neonate with this physiology, systemic oxygen delivery is optimized by
      manipulating pulmonary and systemic resistances, augmenting total cardiac output,
      and utilizing strategies for ventilation that preserve optimal pulmonary
      recruitment.

PMID- 15244141
TI  - Use of routine ventricular assist following the first stage Norwood procedure.

PMID- 15244142
TI  - Surgical palliation of hypoplastic left heart syndrome: is there a role for
      hypothermic circulatory arrest?

PMID- 15244143
TI  - Antegrade regional cerebral perfusion.

PMID- 15244144
TI  - Achieving resonance in a programme for congenital cardiac surgery.

PMID- 15244145
TI  - Cardiac transplantation for hypoplastic left heart syndrome.
AB  - Future improvements can be expected in cardiac transplantation in children. We
      continue to advance our understanding of the immune system, and to develop more
      specific immunosuppressive agents. Ultimately, the future for recipients may be
      improved by strategies such as induction therapy or donor-derived chimeric
      destined transfusions, designed to enhance the tolerance of the host to a human
      leukocyte antigen incompatible graft. Improvements in tolerance of the host would
      allow for reduction or elimination of many, if not all, of the immunosuppressive
      agents, and for longevity extending well into the adulthood. Survival,
      particularly for infants, has improved dramatically in the last decade. The most
      recent results from the registry of the International Society of Heart and Lung
      Transplantation/United Network for Organ Sharing show that recipients less than
      one year old at transplantation, who survive the first year, have greater than a
      95% survival to four years (Fig. 1). As late outcomes continue to improve,
      transplantation will provide a better quality and duration of life for infants
      with hypoplastic left heart syndrome. It is possible, nonetheless, that some
      infants will require retransplantation, since the half life of a transplanted
      heart in children has been about 12 years. The alternative is conventional
      surgery with multiple palliative operations, and the need for later
      transplantation as end-stage cardiac function is reached. Efforts to increase
      potential donors and donor utilization can be supported by innovative schemes,
      such as ABO incompatible transplants. Additional efforts are made more urgent
      when the current data indicate excellent outcomes after transplantation, but a
      high mortality while waiting for transplantation.

PMID- 15244146
TI  - Echocardiographic evaluation before and after cardiac transplantation.

PMID- 15244147
TI  - Advances in methods for surveillance of rejection.

PMID- 15244148
TI  - Indications, criterions, and principles for biventricular repair.

PMID- 15244149
TI  - Biventricular repair in the management of hypoplastic left heart syndrome.

PMID- 15244150
TI  - Staged reconstructive surgery--the most appropriate therapy for hypoplastic left
      heart syndrome.

PMID- 15244151
TI  - Transplantation is the best treatment for hypoplastic left heart syndrome.

PMID- 15244152
TI  - Long-term follow-up after staged reconstruction or transplantation for patients
      with functionally univentricular heart.

PMID- 15244153
TI  - Achieving a balance in the current approach to the surgical treatment of
      hypoplastic left heart syndrome.
AB  - In the modern era, it is possible to achieve programmatic balance in the approach
      to the treatment of hypoplastic left heart syndrome by offering staged
      palliation, transplantation, and in suitable cases, biventricular repair.
      Strategies for optimal selection should continue to improve and evolve. Overall,
      the current hope for survival, and excellent quality of life, for patients with
      hypoplastic left heart syndrome and other forms of functionally univentricular
      heart is better than ever before. Pioneering efforts allowed what we achieve
      today. Our challenge is to continue to improve the surgical and medical care of
      these patients towards normalization of survival and quality of life for future
      generations. These goals will be achieved by capitalizing on current advances in
      the field, and continuing to "push the envelope", with research into new
      advances.

PMID- 15244154
TI  - [Electrodiagnosis, EMG, ENMG...: what do the future and the past tell us about
      the present?].
AB  - Neuromuscular imagery (NMI) of the future significantly extends the possibilities
      of nerve and muscle disorders investigation. It emphasizes some technical
      limitations inherent to electroneuromyography (ENMG) at the beginning of the 21st
      century, but also shows some progress that could have already been made to
      improve the quality of examination, as well as its comfort. In return, the
      history of these techniques points out a misunderstanding, by which
      electrodiagnosis and functional NMI have been asked to show morphological
      lesions, whereas their basic role is to highlight functional abnormalities that
      could account for patient complaints. Analysis of some frequent
      misinterpretations indicates that the functional point of view of ENMG and NMI
      requires to follow a suitable terminology, related to the anatomo-clinic one, but
      distinct from it. On the other hand, the example of purely functional
      abnormalities, like neuromuscular block, nerve conduction block and muscle
      excitability block, suggests that all electrophysiological abnormalities should
      be understood as membrane dysfunctions, before wondering whether they occur alone
      or accompanied with histological lesions. According to this specific point of
      view, the missions of present ENMG and future NMI are firstly to give patients an
      explanation of their complaints in terms of functional abnormalities, and
      secondly to try to bind these abnormalities to pathophysiological mechanisms
      defined at an anatomic level or at a molecular level.

PMID- 15244155
TI  - [Mechanisms which control the peripheral nerve excitability].
AB  - Peripheral nerve excitability is currently tested via the strength/duration
      curves, and by measuring the minimal intensity level (rheobase) of an efficient
      stimulation, and the minimal duration (chronaxy) for a stimulus equal to two
      times the minimal threshold. New "threshold tracking techniques" were recently
      described (Bostock et al., 1991), which afford an automatic evaluation of nerve
      excitabilty. These methods investigate the mechanisms responsible for the
      membrane potential: passive ionic currents, activity of ionic pumps like the Na-K
      ATPase; and the dynamic behaviour of large conductance sodium, potassium, and
      calcium channels, responsible for the generation and conduction of action
      potentials. Results obtained must however be evaluated taking into account the
      following items: stimulation is delivered through the skin and subcutaneous
      tissue; a nerve trunk is explored, and not a single fiber; most often the
      response is recorded over a muscle, hence through neuromuscular synapses.

PMID- 15244156
TI  - [The differential diagnosis of amyotrophic lateral sclerosis].
AB  - The diagnosis of amyotrophic lateral sclerosis (ALS) is mainly a clinical one.
      Nonetheless, electrophysiological studies must be performed early in order to
      confirm the diagnosis. The El Escorial criteria for the diagnosis of ALS,
      recently revisited in order to increase their sensitivity, have been widely
      accepted and help neurologists to categorize patients into various levels of
      certainty from clinical assessment. However, the variability in clinical findings
      early in the course of the disease and the lack of any biological diagnostic
      marker make absolute diagnosis difficult. In this review, I propose a strategy
      for establishing differential diagnoses when faced to a pure motor deficit at the
      first evaluation, or at the electrophysiological study or during follow up.

PMID- 15244157
TI  - [Clinical neurophysiology for estimation of progression and prognosis in ALS].
AB  - The role of clinical neurophysiology in the evaluation of disease progression in
      ALS has to be precised. To be included in the methodology of therapeutic trials,
      neurophysiological methods have to be quantitative, sensitive and reproducible.
      Their goal is to assess peripheral and central motor neuron loss but also
      compensatory processes such as reinnervation. The peripheral motor neuron loss
      can be evaluated by compound muscle action potential amplitude and mainly by
      motor unit number estimate (MUNE). Peripheral reinnervation can be evaluated by
      fiber density and macro-MUP amplitude. Functional aspects of reinnervation can be
      assessed by jitter measurement or the occurrence of decrement when using
      repetitive stimulation. Central motor neuron loss can be evaluated by
      transcranial magnetic stimulation and the triple collision technique (TST). Among
      the various electrophysiological approaches, MUNE and TST seem to be the most
      appropriate to evaluate peripheral and central motor neuron loss over time in
      ALS.

PMID- 15244158
TI  - [Advantages and limitations of the motor unit number estimation techniques].
AB  - It is now 30 years since the first motor unit number estimation (MUNE) technique
      was introduced by Allan McComas as a way of providing an objective, sensitive and
      reproducible means of measuring the number of motor axons in living human muscle
      or muscle group. MUNE techniques have substantially evolved over the past decade
      and have been applied, with increasing frequency, to the study of age effects on
      motoneurone population and muscle denervating disorders such as amyotrophic
      lateral sclerosis (ALS), spinal muscular atrophy, poliomyelitis and different
      types of inherited and acquired peripheral neuropathies. In the future, one of
      the most important topics involving MUNE, will probably be its use in monitoring
      the progress of ALS patients undergoing experimental drug trials. However, among
      incremental, multiple point stimulation, spike-triggered averaging, F-wave
      analysis and statistical methods, there is no consensus about the best MUNE
      method. There is only a general feeling that some techniques are more valid than
      others. For this reason, in the present review, brief descriptions of the
      distinct MUNE methods are presented. In the second part of the paper, advantages
      and limitations (alternation, sampling errors, temporal registration etc...) of
      the most commonly employed procedures are considered.

PMID- 15244159
TI  - [Microtraumatic peripheral neuropathies in sports].
AB  - The microtraumatic peripheral neuropathies encountered during athletic activities
      are not related to a specific sport, and are induced by overuse or forced
      constraints as seen in scapular syndromes, in distal neuropathies of upper and
      lower limbs, and in the foot. These neuropathies are less frequently seen than
      those following direct traumatic conditions. The constant increase in sport
      activities in the general population implies that each neurologist should ask for
      athletic habits of his patient in order not to miss the repetitive activities
      that can induce an atypical nerve injury. Electrodiagnostic (ENMG) studies in the
      background of sporting activities are performed in similar ways as in a general
      setting, but the synthesis may be more complex in relation to frequent associated
      orthopaedic disorders. ENMG studies are useful in the diagnosis of pain syndromes
      with or without paresthesia in sports-related nerve injuries.

PMID- 15244160
TI  - [Anterior interosseous nerve lesions revisited in 2004].
AB  - When the anterior interosseous nerve (AIN) is involved, a motor deficit of the
      distal pinch appears. It usually occurred suddenly, with or without pain and the
      deficit may be complete or partial. Other nerve lesions and some precipitating
      conditions can be noticed and are important to assess the exact mechanism of the
      nerve lesion. Partial AIN lesion is frequently misdiagnosed as tendon rupture.
      The electrodiagnostic examination should always study the pronator quadratus or
      another muscle innervated by the AIN, the AIN conduction and the motor and
      sensory median nerve conduction. Thus electrodiagnosis will always assess the AIN
      lesion and precise its axonal or compressive mechanism. Mononeuritis as neuralgic
      amyotrophy is the most frequent cause of AIN palsy and never requires surgery.
      Traumatic lesions are less frequent and usually recover spontaneously. Thus,
      surgery is rarely required before 12 to 18 months except when no recovery occurs
      after trauma.

PMID- 15244161
TI  - [Topographic and functional anatomy of cranial nerves].
AB  - This review summarizes the descriptive anatomy of cranial nerves III through XII,
      starting at their emergence from the neuraxis towards peripheral territories, as
      well as their functional anatomy. For each pair of cranial nerves, correlations
      are made between diseases, anatomo-clinical and anatomo-neurophysiological data.

PMID- 15244162
TI  - [Electrophysiological examination of the cranial nerves: technical aspects and
      practical applications].
AB  - Electrophysiological investigations of cranial nerves have long been limited to
      conventional electromyography, but recently have undergone new developments.
      Brainstem reflex testing is now well defined with correlations to imaging data.
      Brainstem reflexes can be tested in trigeminal and facial nerve diseases, but
      also in the case of intra-axial lesions. Surface neurography has developed to
      quantify troncular nerve responses, abnormal facial nerve responses or assessment
      of neuromuscular junction function through repetitive stimulation. Transcranial
      magnetic or electrical stimulation allows to functionnally investigate proximal
      cranial nerve segments as well as central pathways. Intra-operative monitoring of
      various cranial nerves can be useful but techniques still need to be validated.
      Therapeutic use of botulinum toxin involves the electromyographist, as well for
      the diagnosis as for EMG-guided injections.

PMID- 15244163
TI  - [The hypolossal-facial anastomosis in man. A model for studying peripheral and
      central nervous system plasticity].
AB  - Hypoglossal-facial anastomosis (HFA) is a cross-over between the proximal stump
      of the hypoglossal nerve (XII) and the distal one of the facial nerve (VII). The
      hypoglossal axons regrow within the sheaths of facial fibres, allowing the
      progressive reinnervation of the facial muscles. This model is interesting to
      study some mechanisms of plasticity of the nervous system for several reasons: 1)
      It is a quite simple and reproducible model of pathophysiological state. It
      allows the study of 2) the modifications of the nervous system induced by the
      HFA, both upwards and downwards to the lesion and 3) the modifications of reflex
      activities involving intrapontine connections such as the blink reflex. The
      electrophysiological features of the trigemino-facial (TF) and trigemino
      hypoglossal (TG) connections demonstrated that a central reorganisation of the
      blink reflex (BR) was induced by HFA: the afferent volleys of the TF and TH
      reflexes elicited by cutaneous and mucosal trigeminal afferents respectively have
      been shown to project onto common interneurones located within the trigeminal
      principal sensory nucleus. A long-term prospective study showed: 1) a
      reinnervation of the facial muscles by the hypoglossal axons is a necessary
      perequisite for the central reorganisation of BR, 2) a hyperinnervation of the
      facial muscles by the hypoglossal axons, 3) a transient and regressive cross
      innervation of paralyzed face by the healthy contralateral facial nerve.

PMID- 15244164
TI  - [Vasculitis and diseases of the peripheral nervous system].
AB  - Vasculitis commonly induces peripheral neuropathies. Neuropathy is isolated in
      one third of the cases or participates in a multisystemic disorder. The
      pathological mechanism is tissular ischaemia induced by inflammation and lesions
      of vessel walls. Pathophysiological classification of vasculitis is mainly based
      on the size of affected vessels but other approaches may be proposed such as
      immunological classification considering the presence or absence of immunological
      markers. The diagnosis is supported by neuropathological examination of muscle
      and nerve biopsies, but electrophysiological testing may contribute to establish
      the diagnosis and the prognosis of the disease by showing the highly suggestive
      pattern of multitroncular involvement and by evaluating the extent of the
      neuropathy and of axonal loss. In most cases, treatment with steroids and other
      immunosuppressive agents result in good but partial improvement.

PMID- 15244165
TI  - [Neurophysiology of systemic diseases].
AB  - Connective tissue diseases represent a varied and challenging group of disorders.
      Neuromuscular structures are highly susceptible targets for damage. In this
      review, the neurophysiological explorations of the neuromuscular complications
      are examined with particular attention to the peripheral nerve system. The most
      common presentations are sensorimotor polyneuropathy, mononeuritis multiplex,
      distal symmetric neuropathy, compression neuropathy and trigeminal sensory
      neuropathy.

PMID- 15244166
TI  - [How to clinically and electrophysiologically diagnose hereditary
      polyneuropathies without a family history?].
AB  - Sporadic cases of hereditary neuropathies are not uncommon. The most frequent
      clinical pictures are purely or predominantly motor neuropathies. A hereditary
      neuropathy of Charcot-Marie-Tooth should be suspected in the following
      situations: presence of scoliosis and pes cavus, distal weakness with forearm and
      leg distal muscle atrophy, discrepancy between relatively mild motor deficit and
      severe atrophy or markedly reduced spatial recruitment on needle EMG examination,
      severely altered sensory nerve action potentials with subtle sensory symptoms
      and, in the demyelinating type, homogenous slowing of nerve conduction in distal
      and proximal segments (normal terminal latency index), and between nerves of a
      same region or between axons of the same nerve (absence of temporal dispersion).
      Amyloid neuropathy should be considered in case of axonal sensori-motor
      polyneuropathy of subacute course, with autonomic dysfunction, plantar ulcers
      and/or subclinical carpal tunnel syndrome. Hereditary neuropathy with liability
      to pressure palsies usually gives a picture of multifocal neuropathy with nerve
      conduction slowing at usual compression sites. Finally, purely sensory hereditary
      neuropathies are rare and seldom cause diagnostic problems.

PMID- 15244168
TI  - [Value of electrophysiology in the follow-up of dysimmune polyneuropathies].
AB  - Electrophysiological follow-up of dysimmune neuropathies leads to consider
      various situations depending on the type of neuropathy. In Guillain-Barre
      syndrome, studies have highlighted the usefulness of early measurements of distal
      motor latencies and late responses at onset of paralysis, and of motor conduction
      velocities (MCVs), conduction blocks, sensory nerve action potentials and
      possible signs of axonal degeneration at the plateau of symptoms. However, none
      of these signs are predictive of clinical recovery, except early appearance of
      axonal degeneration which often indicates poor prognosis. In chronic inflammatory
      idiopathic demyelinating polyneuropathies, the follow-up mostly relies on motor
      conduction studies: increase or slowing of MCVs, shortening or prolongation of
      distal motor latencies, improvement or lengthening/disappearance of late
      responses and, more ancillary, sensory nerve action potential changes. Signs of
      axonal degeneration can worsen the prognosis. In multiple motor neuropathies with
      persistent conduction blocks, the most relevant electrophysiological criterion is
      increase or reduction of conduction blocks, as well as occurrence of new blocks
      and signs of axonal degeneration. In neuropathies associated with IgM monoclonal
      gammopathy of undetermined significance (MGUS) with anti-MAG antibodies, the
      electrophysiological follow-up mostly relies on the comparison between MCVs and
      distal motor latencies, as well as improvement or worsening of sensory nerve
      action potential amplitudes, and possible signs of axonal degeneration. In all
      those neuropathies however, therapeutic choices remain largely dependent on
      clinical scores, which have become increasingly standardized in recent years,
      although scales used by different groups are not universally accepted.

PMID- 15244167
TI  - [Neurotoxic effects of medications: an update].
AB  - Peripheral neuropathy is a common neurotoxic effect of medications.
      Antineoplastic agents and antiretroviral medications are most often involved:
      platinum compounds, vinca alkaloids, taxols and nucleoside reverse transcriptase
      inhibitors. These agents cause a dose-related axonal polyneuropathy. Symptoms are
      indicative of a predominantly sensory or sensory-motor neuropathy which in some
      cases is accompanied by dysfunction of autonomic nervous system. Depending on
      dosage and agent used symptoms resolve completely or not. Neurotoxic effect can
      appear immediately during or shortly after administration of the drug but
      sometimes after cessation of chemotherapy. In all cases the neuropathy alters the
      quality of life. A general predisposition for developing a neuropathy has been
      observed in nerves previously damaged by diabetes mellitus, alcohol or in
      inherited neuropathy. Within the past five years, some cases of neuropathy caused
      by alpha-interferon, statins or tacrolimus have been reported. Although rare,
      these aetiologies should be considered by physicians and the drugs removed when
      others causes of neuropathy have been excluded. Few cases of peripheral
      neuropathy have been recently reported with metronidazole, dapsone,
      nitrofurantoin or colchicin. Thalidomide induces a dose-dependant sensori-motor
      length-dependent axonal neuropathy. It should be judiciously used with close
      neurologic monitorin. Little is known about the mechanisms responsible for the
      development of neuropathy. Up to now, no drug is available to prevent or cure
      drug-induced neuropathies.

PMID- 15244169
TI  - [Contribution of autoantibodies to the diagnosis of peripheral neuropathies].
AB  - The identification of autoantibodies associated with dysimmune neuropathies was a
      major contribution to the characterisation of peripheral nerve disorders, the
      understanding of their pathophysiology, and the clinical diagnosis of
      neuropathies. This review focuses essentially on the interest of these antibodies
      in clinical practice. The methods used for their detection, their specificity and
      sensitivity is the first point to take into account. The second is the aim of the
      antibody detection, pathophysiological or diagnostic. The last is to adapt the
      search for antibodies to the clinical characteristics of the neuropathy.
      Antibodies directed to GM1, GQ1b and disyalilated gangliosides, and anti-MAG
      antibodies are very useful in the diagnosis of acute or chronic motor or sensory
      motor neuropathies with or without monoclonal IgM. Anti-onconeural anti-Hu and
      anti-CV2/CRMP antibodies allow when they are detected the diagnosis of
      paraneoplastic neuropathies. Neuropathies also occur in the setting of systemic
      diseases. Detection of antibodies associated with these diseases such as ANCA,
      soluble nuclear antigens, gliadin, or mitochondry may be helpful in the diagnosis
      of neuropathies.

PMID- 15244170
TI  - [Single-fibre electromyography].
AB  - Single-fibre electromyography (SF-EMG) is the most sensitive electrophysiological
      test for myasthenia gravis and other neuromuscular junction pathology. It is also
      useful in the assessment of motor unit morphology in some neuromuscular diseases.
      A special needle with a 25 microm recording surface is used to record the time
      locked potentials of 2 muscle fibers belonging to the same motor unit. Jitter is
      the variability in the arrival time of action potentials to the recording surface
      between consecutive discharges. The junctional part of the jitter depends on the
      amount of Ach released and on the sensitivity of the postsynaptic membrane and is
      related to the safety margin of neuromuscular transmission. Thus, SF-EMG can
      detect subclinical impairment of neuromuscular transmission, which cause an
      increased jitter. However, an increased jitter is not specific of neuromuscular
      transmission disorders, because it may be due to unstable conduction in motor
      nerves and muscle fibers. It is the extrajunctional part of the jitter. SFEMG is
      performed either during slight voluntary contraction (volitional SFEMG) or by
      axonal stimulation (stimulated SFEMG). Jitter is expressed as the mean of the
      absolute consecutive differences (MCD) of the latency between the time-locked
      potentials (volitional SFEMG) or from the stimulus to the negative peak of the
      potential (stimulated SFEMG). Recording is judged abnormal when more than 10% of
      the collected pairs are abnormal. On the other hand, single use coaxial needle
      electrodes which are cheaper could be an alternative for neuromuscular
      transmission analysis, because the jitter analysed with this type of needle was
      found highly comparable to that analysed with SF electrode. Moreover, jitter
      measurements coupled with fiber density estimates provide valuable information on
      the pathophysiology of the motor units in various neuromuscular disorders.

PMID- 15244171
TI  - [Neurophysiological investigations of respiratory function].
AB  - Neurophysiological assessment of breathing is mandatory for the diagnosis and
      management of respiratory problems occurring in neuromuscular disorders
      (neuromuscular complications of critical illness, spinal cord trauma, C4-C5
      radiculopathies, phrenic nerve neuropathy, diabetes mellitus, Guillain-Barre
      syndrome etc...). We review the methods of exploration (principles and normative
      data) of efferent pathways (phrenic nerve conduction, central motor conduction
      studies with transcranial magnetic stimulation, diaphragmatic EMG) and afferent
      pathways (somatosensory evoked potentials of the phrenic nerve, respiratory
      evoked potentials, sympathetic skin response during sudden occlusion of
      respiratory pathways during inspiration), as well as their main indications.

PMID- 15244172
TI  - [Somatosensory evoked potentials: clinical applications in peripheral
      neuropathies].
AB  - Somatosensory evoked potentials (SSEP) offer a reliable measurement of peripheral
      and central sensory conduction through the stimulation of mixed or purely
      sensitive nerves. If their interest is well known for the evaluation of central
      pathologies (cerebral or spinal), their precise indication and application field
      in peripheral neuropathies remains unclear. Some specific diseases, like lumbar
      or cervical radiculopathies or brachial plexopathies, have been extensively
      studied and large series have been reported in the literature. Relative
      sensitivity and specificity of SSEPs and electroneuromyography (ENMG) is a matter
      of debate for specific peripheral nerve affections. We present a practical
      approach in which SSEPs and ENMG data are integrated toward a better diagnosis.
      Clinical histories are exposed as an illustrative demonstration of specific
      interest for combined SSEPs and ENMG in the patient's functional evaluation and
      follow-up.

PMID- 15244173
TI  - [Clinical applications of repetitive transcranial magnetic stimulation].
AB  - Transcranial magnetic stimulation (TMS), when delivered in trains of pulses is
      able to induce long-lasting changes of excitability of neuronal networks, not
      only in the vicinity of the stimulating coil, but also at distant sites. Results
      of stimulation experiments over the motor cortex indicate that the effects
      (excitatory or inhibitory) depend on the frequency of stimulation. These data
      have prompted researchers to use repetitive transcranial magnetic stimulation
      (rTMS) as a therapeutic tool in various brain disorders, most notably depression.
      However, as long as large randomized trials have not been conducted, rTMS cannot
      be recommended as an alternative to validated conventional therapies of such
      disorders.

PMID- 15244174
TI  - [Surface electromyography procedure].
AB  - Surface electromyography (SEMG) is not yet able to substitute needle EMG for
      diagnosing neuromuscular diseases in our current clinical neurophysiological
      practice. Several research groups have been working to reach this goal. Thus, we
      already have available, though imperfect and open to criticism, tools to apply
      SEMG to follow-up studies of neuromuscular diseases. There are enough scientific
      data to integrate validated tools into EMG equipment, to provide recommended
      electrodes and developed techniques and methods for recording and analysing all
      SEMG components, so that we could study the suggested standardised parameters in
      our clinical routine context. Independently of the accuracy of clinical
      indications for the chosen methods, the requirements of sensitivity, specificity
      and reproducibility should be as substantial for ENG as for needle or surface
      EMG. They suppose an equal demanding procedure in doing exams and interpreting
      results. The respective contribution of ENG and needle or surface EMG is still to
      be confirmed. Respective value and limitations of the force measurements by
      manual or quantitative testing, functional scales, SEMG or motor unit number
      counting are not yet evaluated in follow-up studies of neuromuscular diseases.

PMID- 15244175
TI  - [Electrodiagnostic assessment of neuromuscular junction disorders].
AB  - Electrodiagnosis of neuromuscular junction disorders relies on repetitive nerve
      stimulation tests (RS) and single-fiber EMG (SFEMG). RS tests are usually
      performed on proximal and distal nerves (axillary, accessory, radial, facial,
      ulnar, median, peroneal). Ischemic test substantially improves ulnar RS
      sensitivity. More recently RS of masseter and hypoglossal nerves have been
      proposed to increase RS sensitivity in patients with bulbar symptoms in
      myasthenia gravis (MG). RS of phrenic and long thoracic nerves could be used in
      MG patients with respiratory symptoms. Sensitivities of these tests are widely
      different but they are complementary. SFEMG is far more sensitive but technical
      difficulties have limited its use. In generalized MG, RS should be performed
      first. Clinically involved muscles should be examined first, then other muscles.
      If RS tests are negative, SFEMG of facial muscles can be used. In ocular MG,
      SFEMG, if available, is the best option. In Lambert-Eaton myasthenic syndrome, a
      single shock on ulnar nerve before and after a brief maximum voluntary
      contraction should be used to demonstrate increment and 3 Hz RS a decrement. If
      negative, median and radial nerves should be studied. Additionally
      electrodiagnosis features of congenital myasthenic syndromes and botulism are
      reviewed.

PMID- 15244176
TI  - [The role of electrodiagnostic studies in the diagnosis of hypotonia in infancy].
AB  - Increased muscle extensibility and passivity characterize infantile hypotonia. It
      may reveal a peripheral neuromuscular disease as well as a disorder of the
      central nervous system. Electrodiagnostic studies in newborn and young infants
      are useful to guide the indication of other complementary investigations. Signs
      of denervation on needle electromyography strongly suggest infantile spinal
      muscular atrophy. Electrodiagnostic findings can distinguish rare conditions
      mimicking spinal muscular atrophy that are obstetrical tetraplegia and severe
      congenital neuropathies. Nerve conduction velocities are severely slowed in
      hereditary sensorimotor neuropathies and neurodegenerative disorders. Myopathic
      changes on needle electromyography are associated with congenital muscular
      dystrophies and structural or metabolic congenital myopathies. In congenital
      myotonic dystrophy, myotonic discharges can be recorded in the infant as well as
      in his/her mother. Myopathic changes may also be detected in collagen disorders,
      in cases of muscular atrophy secondary to hypomotility or malnutrition, and in
      patients with congenital myasthenic syndrome. Repetitive nerve stimulations are
      required to characterize myasthenic syndromes. Finally, normal results of
      electrodiagnostic studies constitute a relevant information that moves diagnostic
      procedures to search for central nervous system disorders. Benign congenital
      hypotonia is a quite rare condition that is diagnosed retrospectively, when
      hypotonia is strictly isolated and recovers completely before 2 years of age.

PMID- 15244177
TI  - [Strategies to interpret late waves in routine neurophysiology].
AB  - A number of late waves other than F and H spinal waves are commonly observed
      during motor nerve conduction studies. Simple criteria are available that allow
      an understanding of their origin and significance. A late wave can be
      characterized by 1) its origin, proximal or distal to the stimulator, 2) its
      position with reference to the spinal waves, 3) its latency, stable or not, 4)
      its appearance in response to all (constant) or not to all stimuli (inconstant),
      5) its persistence or not to intense stimuli, 6) its relative threshold, 7) its
      behavior to paired stimuli (namely if it is or not evoked twice by paired
      stimuli). By use of these criteria, one may distinguish the late waves that are
      evoked proximal to the stimulator (indirect late waves), such as the spinal
      responses (H and F), the motor axon reflex and the indirect double discharge,
      from those late waves that originate distally to the stimulator (direct late
      waves) such as the late potential, the myo-axonal ephaptic response and the
      direct double discharge. Signification of these late waves in relation to
      peripheral nerve disorders is discussed. Late potentials, motor axon reflex and
      ephaptic myo-axonal responses are signs of a prior axonal lesions, whereas
      indirect double discharges relate to an ongoing demyelinating process.

PMID- 15244178
TI  - [Neuropathy versus neuronopathy: distinctive features].
AB  - Neuropathy may be difficult to distinguish from neuronopathy, on both motor and
      sensory sides. A number of disorders that present with characteristic electro
      clinical features are readily recognized. Except for those, distinction of the
      lesions that concern the peripheral nerve cell or the axon may require support of
      clinical, electrophysiological and other ancillary tests. Distinction between
      motor neuropathy and neuronopathy can be based on the abnormalities of nerve
      conduction and on the signs that relate to the reinnervation process. Signs of
      terminal axonal reinnervation, such as motor axon reflex, may be observed in
      axonal neuronopathies, whereas only collateral reinnervation occurs in motor
      neuronopathies. Sensory axonopathies are usually characterized by clinical and
      electrophysiological findings that are axon length-dependent, by the course of
      the disorder that is most often chronic, and by possible reversibility. Sensory
      neuronopathies are usually subacute and induce clinical deficits that are more or
      less widespread to the whole body surface rather than distal. Follow-up studies
      disclose limited or absent recovery. A better knowledge of the structural
      differences of motor and sensory neurons and axons will improve our understanding
      and lead to the development of specific tests. Meanwhile, although some
      parameters and techniques should still be improved, electrophysiological and
      additional tests are useful to detect and to distinguish the peripheral nerve
      disorders that affect the nerve cell bodies and their axons.

PMID- 15244179
TI  - Thermic ablation with RF of liver metastases from colorectal cancer.
AB  - Aim of this study was to evaluate the role of radiofrequency ablation in the
      treatment of the hepatic metastasis of colorectal cancer. From November 1997 to
      July 2002 49 radiofrequency ablations have been performed in 19 patients (11 male
      and 8 female; mean age 65 years: range 50-78 years). The disease-free period was
      between 5 and 32 months. Nodules had a diameter <3 cm in 4 cases while in 3 cases
      a single lesion was present. One patient had a single lesion after 2 courses of
      intravenous systemic chemotherapy which had a reduced greater lesion (from 6 to 3
      cm) while a 2 cm lesion had disappeared. In the remaining 12 patients the mean
      number of lesions is 3 (range 1-13) with a diameter between 3 and 12 cm. The
      radiofrequency ablation has been performed during laparotomy and vascular
      exclusion through clampage of the liver hilum in 4 cases and percutaneously under
      ultrasound guide in the remaining 15 cases. All patients underwent follow up by
      computed tomography, CEA level and ultrasound every 3 months. One patient only
      has completed a 4 year follow up and is alive without local recurrence but with a
      cerebral metastasis. The other 18 patients have a 32 months follow up with a
      survival of 50% (9 on 18). In conclusion in our experience the radiofrequency
      ablation is a valid alternative method in the treatment of the hepatic metastasis
      of colorectal cancer.

PMID- 15244180
TI  - The clinical value of the procalcitonin in prediction of severity and outcome in
      acute pancreatitis.
AB  - BACKGROUND/AIMS: Early identification of patients with severe forms of acute
      pancreatitis (AP) and subsequent management of these high risk patients are the
      most important aims in order to decrease mortality from AP. Procalcitonin (PCT)
      as a marker for systemic inflammation appears to be a useful marker for early
      identification of severe forms. METHODOLOGY: 101 patients with confirmed AP have
      been admitted to department of general surgery. PCT values were measured in each
      patient on admission and after 12 hours. PCT levels were correlated to the
      disease's course and prognosis. Results are given through PPV and NPV.
      Immunoluminometric assay (BRAHMS Diagnostica) was used for measurement. RESULTS:
      PPV and NPV for prediction of disease's course were better for PCT than for CRP
      PPV 64.7% versus 36% and NPV 82,6% versus 79.6% and for prediction of fatal
      outcome PCT reached 75% and 100% for cut off value 5 ng/ml. CONCLUSIONS: PCT
      seems to be a useful screening parameter for detecting severe AP and for
      identifying the patients who need ICU treatment, ATB covering and who can benefit
      from the novel therapies.

PMID- 15244181
TI  - Intrahepatic Osler's disease: report of two cases and review of the literature.
AB  - Osler-Weber-Rendu disease is a hereditary vascular disease with multiple
      manifestations. The liver is involved rarely. Vascular abnormalities include
      telangiectasis and arteriovenous fistulas, sometimes associated with fibrosis and
      cirrhosis. Hepatic arteriovenous shunting may include secondary portal
      hypertension, reduced liver function and high cardiac output. Two cases of Osler
      Weber-Rendu disease with extensive hepatic arteriovenous fistulation were
      described in detail and we report on their clinical features. In the first
      patient, treatment was symptomatic since liver transplantation is not indicated
      because the patient was asymptomatic. Embolization treatment of hepatic arteries
      was indicated in the second patient because he had biliary disease and recurrent
      cholangitis secondary to vasculo-biliary shunts. Therapy with arterial
      embolization, banding, or ligature of hepatic arteries is still limited and
      provides unsatisfactory long-term results. Liver transplantation offers now
      another therapeutic option for patients with intrahepatic high shunting and
      secondary pulmonary hypertension.

PMID- 15244182
TI  - Sentinel lymph node biopsy with 99mTC tin-colloid in patients with gastric
      carcinoma.
AB  - BACKGROUND/AIMS: The sentinel lymph node (SLN) is defined as the first draining
      node from the primary lesion. The objective of this study was to determine the
      feasibility of SLN biopsy in patients with gastric cancer for assessment of lymph
      node status. METHODOLOGY: From November 2001 through to July 2002, SLN biopsy was
      performed in twenty-two consecutive patients whose preoperative imaging studies
      showed T2 or T1 and no lymph node metastasis. Three hours prior to each
      operation, 99mTc tin-colloid (2.0ml, 1.0mCi) was injected into the submucosa of
      gastric tumor via endoscope. After SLN biopsy had been performed using gamma
      probe (NEO2000 Gamma Detection System, Neoprobe CO, 1999, USA), all the patients
      underwent radical gastrectomy. The SLN was cut and immediately manipulated for
      frozen section, and processed to make paraffin block for H&E and
      immunohistochemistry (IHC) staining. RESULTS: On average, 1.8 (range 1-5) SLNs
      were identified per patient. The location of all SLNs was in the perigastric
      area. No skip metastases were found. SLNs were identified in 20 of the 22
      patients (success rate, 90.9%). The sensitivity of the SLN status in the
      diagnosis of the lymph node status was 82.2% (5/6) and the specificity was 100.0%
      (14/14). The diagnostic accuracy according to SLN status was 95.0% (19 of 20).
      CONCLUSIONS: SLN biopsy using radioisotope in patients with gastric cancer was a
      technically feasible procedure and a minimally invasive approach in the
      assessment of the nodal status in each patient.

PMID- 15244184
TI  - The effects of nitric oxide synthase blockers on mesenteric blood flow with bile
      duct ligation.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effects of nitric
      oxide synthesis inhibition by L-NNA (N-nitro-L-arginine) on mesenteric blood flow
      in bile duct ligated rats. METHODOLOGY: Forty female Wistar rats were allocated
      into four groups. Only common bile duct (CBD) was dissected with midline
      laparotomy (sham operated), CBD is ligated for obstructive jaundice (OJ group),
      with CBD dissection, 20 mg/kg L-NNA was given i.p. during 14 days (sham + L-NNA
      group), after CBD ligation, 20 mg/kg L-NNA was given i.p. during 14 days (OJ + L
      NNA group). At the end of the 14th day, the rats were re-anaesthesized,
      phenylephrine was administered within the left jugular vein and, arterial blood
      pressure monitorization was done via left carotid artery. Blood flow of the
      mesenteric artery (SMA) was also recorded. Resistance of the SMA was calculated
      and in addition, pressure responses to phenylephrine were detected.
      Histopathological examination of the liver and blood analyses were done. RESULTS:
      The mean blood pressure levels of the rats with OJ were lower than the control
      group (P>0.05). Blood flow of the SMA and vascular resistance of the rats with OJ
      have no significant difference with other groups. In CBD ligated animals, mean
      blood pressure and mesenteric vascular resistance increased by L-NNA but there
      was no difference in mesenteric blood flow rate and vasoconstrictive response to
      phenylephrine. On microscopic examination of the liver with OJ, bile duct
      proliferation and minimal mononuclear reaction were observed which was not
      affected by L-NNA administration. CONCLUSIONS: Hypotension, low systemic vascular
      resistance, and a reduced sensitivity to vasoconstrictors are features of
      cirrhosis. In obstructive jaundice impaired vascular responsiveness to
      vasoconstrictor stimuli like as cirrhosis was not observed and also there was no
      improvement by L-NNA on histopathologic findings and liver function tests.

PMID- 15244183
TI  - Primary tumors of the small bowel: diagnosis, treatment and prognostic factors.
AB  - BACKGROUND/AIMS: The neoplasms of the small intestine are rare and the
      preoperative diagnosis is difficult. The aim of this study is to review
      difficulties in diagnosis, treatment options and important prognostic factors.
      METHODOLOGY: Fifteen patients who underwent surgical resection for intestinal
      tumors from 1990 to 2000 in the Third Surgical Clinic of Izmir Ataturk Training
      and Research Hospital were reviewed retrospectively. Age, symptoms, diagnostic
      methods, operative procedures, and their effects on prognosis were evaluated.
      RESULTS: Seven patients were male and eight were female. The mean age was 52.3
      years (27-77). Eight patients underwent urgent intervention and seven had
      elective surgery. Three cases were diagnosed as small bowel tumor preoperatively.
      The radical resection of the small bowel neoplasm was possible in 12 patients
      (80%), eight of whom being malignant and four of whom being leiomyoma. Three
      patients with leiomyoma are still alive for 3.5, 6 and 9 years but one patient
      died perioperatively because of respiratory distress syndrome. Two cases with
      lymphoma survived for 16 and 37 months while another two have been still alive
      for 7 and 8 years. The patients who had malignant epithelial tumor,
      leiomyosarcoma, and malignant mesenchymal tumor survived for 17, 54, and 20
      months, respectively. The patient with malignant tumor of endocrine origin has
      still been living for 3 years. CONCLUSIONS: As a result we concluded that better
      evaluation of signs and symptoms may facilitate the diagnosis; and the most
      important prognostic factors are early diagnosis and radical surgery.

PMID- 15244185
TI  - The toxicity rates of two different regimens of irinotecan.
AB  - The role of chemotherapy in the management of advanced colorectal cancer has been
      well established. Although fluorouracil has been the main cytotoxic agent used
      for colorectal cancer, newer drugs have been developed with promising results. In
      this study, we compared two different doses of irinotecan combined with 5
      fluorouracil/leucoverin (5-FU/LV) in terms of progression-free and overall
      survival time and toxicity in the patients with recurrent or metastatic
      colorectal cancer. Patients were divided into groups. The first group received
      350 mg/m2 irinotecan every three weeks. The second group was treated by 150 mg/m2
      once a week for consecutive four weeks followed by a two-week drug-free interval.
      All the patients received 500 mg/m2 5-fluorouracil and 20 mg/m2 leucoverin every
      time they were treated with irinotecan. Median progression-free survival time was
      found to be 7 +/- 1 and 6 +/- 1 months in the first and seconds groups,
      respectively. Median overall survival time was found to be 19 +/- 4 and 12 +/- 4
      months in the first and second groups, respectively. Alopecia grade 3-4 reaction
      rates were found to be significantly higher in the first group, while
      hematological grade 3-4 toxicity rates were higher in the second group. Although
      overall and progression-free survival curves were found to be similar in each
      group, hematological complications were less and response rates were higher in
      the 3-week course group. The 3-week course seemed to have a more comfortable
      administration schedule as well. So, we suggest the 350 mg/m2 once every 3 weeks
      regimen.

PMID- 15244186
TI  - Serum paraoxonase levels in pancreatic cancer.
AB  - BACKGROUND/AIMS: Serum paraoxonase (PON) is a calcium-dependent esterase that is
      known to contribute to the antioxidant protection conferred by high-density
      lipoprotein (HDL) on low-density lipoprotein (LDL) oxidation. Serum PON activity
      was shown to be reduced in patients with diseases such as myocardial infarction,
      diabetes mellitus, etc in comparison to healthy subjects. However, the relation
      of serum PON levels to cancer is still not known. So, we intended to measure
      serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to
      investigate the relation of serum PON to plasma lipoproteins in the patients with
      pancreatic cancer. METHODOLOGY: We measured serum PON, HDL, LDL, and VLDL levels
      in 20 patients with pancreatic cancer and in 20 age-and gender-matched healthy
      controls. We investigated the relationship between PON and HDL, PON and LDL, and
      PON and VLDL. RESULTS: Serum HDL levels were lower in the patients than in
      controls (40.21 +/- 13.82 mg/dL, and 47.30 +/- 6.65 mg/dL, respectively)
      (p<0.05). Serum LDL and VLDL levels measured in the patient group were not
      significantly different from those of the control group. Serum PON levels were
      lower in the patients than in controls (61.57 +/- 22.44 U/L, and 87.50 +/- 23.39
      U/L, respectively) (p<0.005). There was a positive correlation between serum PON
      and HDL levels (r: 0.69, p<0.05). CONCLUSIONS: We concluded that the patients
      with pancreatic cancer had low PON and HDL levels compared to healthy controls.
      The importance of PON as a predictive risk factor for cancer should be assessed
      in future studies.

PMID- 15244187
TI  - Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer
      patients.
AB  - BACKGROUND/AIMS: in advanced cancer patients a cell-mediated immunological
      impairment, both at baseline and during postoperative period (surgical trauma
      response) is often found and is associated with poor prognosis. Furthermore it is
      well known that cortisol is strictly involved in the response to major surgical
      stress, has an important immunosuppression activity and causes a redistribution
      of immunological population cells in different tissues. The aim of the study was
      to verify serum levels and circadian rhythm of cortisol and ACTH in patients with
      colorectal cancer at baseline before surgery and in the postoperative period, and
      relate it to the immune status. METHODOLOGY: 40 patients (22 female, 18 male with
      a median age of 66 yrs) with histologically proven colorectal cancer undergoing
      to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+,
      cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at
      baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were
      studied in 18 patients. RESULTS: increase of cortisol serum level in the post
      operative period vs baseline was statistically significant both in 3rd and 7th
      days. A significant decrease of total and CD4+ lymphocytes count was found on
      both 3rd and 7th postoperative days compared to baseline and to normal values.
      The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and
      7th postoperative days respectively. At baseline 28% of patients had an altered
      cortisol circadian rhythm and it was significantly more frequent in patients with
      nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18
      patients evaluated for ACTH circadian rhythm displayed an alteration and it was
      significantly higher in patients with nodal involvement and metastatic disease
      (P<0.05). No relations between lymphocytopenia and alteration of night
      cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found,
      neither at baseline, 3rd and 7th postoperative days. CONCLUSIONS: it is known
      that lymphocytopenia, both at baseline and in the postoperative period, is
      associated with a poor prognosis in cancer patients and that cortisol plays an
      important role in the immune response. Our data show that lymphocytopenia often
      present in cancer patients, poor prognostic factor, seems not to be associated
      with ACTH and cortisol level and circadian rhythm alteration, both at baseline
      and after surgical stress. Otherwise even if paraneoplastic syndromes seems not
      to be related to colorectal cancer and no patient showed adrenocortical
      metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at
      baseline in 28% and 44% respectively. It was significantly associated with the
      presence of metastatic disease. These preliminary results suggest further
      investigations on relation between cancer and endocrine system.

PMID- 15244188
TI  - Comparison of the measurement methods of bursting pressure of intestinal
      anastomoses.
AB  - BACKGROUND/AIMS: This study was designed to determine whether there exists a
      difference between in vivo and in vitro measurements of bursting pressure (BP) of
      experimental intestinal anastomosis studied in Wistar-albino rats. METHODOLOGY:
      In the first group (n=8), the BP was measured using in vivo method without
      detaching the adhesions around the anastomosis. BP was determined with digital
      manometer, and then anastomotic region was removed to measure tissue
      hydroxyproline (HP) levels. In the second group (n=8), the BP was measured with
      in vitro method after the segment of intestine including the anastomosis was
      dissected and isolated. The isolated specimen was then submerged in a normal
      saline bath. BP was determined with a digital manometer and anastomotic region
      was removed to measure tissue HP levels. RESULTS: While HP value in the first
      group was 105.60 +/- 9.43 microg/mg dry tissue, it was found to be 121.11 +/-
      16.26 microg/mg dry tissue in the second group and this difference was not
      statistically significant (p=0.195). The BP was determined as 240.71 +/- 11.65
      mmHg in the first group, 144.71 +/- 16.41 mmHg in the second group and the
      difference was statistically significant (p=0.002). The anastomotic resistances
      to intraluminal pressure were found to be statistically different whereas tissue
      HP levels were normal between the groups. CONCLUSIONS: These results make us
      consider that mechanical changes occur about the isolated anastomotic line and
      dissection of adhesions weakens the anastomosis.

PMID- 15244189
TI  - Comparison of the experimental intestinal anastomoses performed by different
      surgeons.
AB  - BACKGROUND/AIMS: This study was designed to determine the effects of different
      surgeons on the experimental anastomosis studied in rats. METHODOLOGY: Sixteen
      Wistar-albino rats were equally separated into two groups. The rats operated on
      by the first surgeon were coded Group 1 and operated on by the other surgeon were
      coded Group 2. Both surgeons were trained on the gastrointestinal surgery. The
      procedure of the study were standardized and dictated to the surgeons. Bursting
      pressure and tissue hydroxyproline content were determined as parameters of the
      anastomotic strength and healing on the seventh day postoperatively. RESULTS: The
      bursting pressures were measured with a digital manometer and anastomotic lines
      were removed to measure tissue hydroxyproline level. While hydroxyproline value
      in the first group was 105.60 +/- 9.43 microg/mg dry tissue, it was found to be
      104.02 +/- 17.26 microg/mg dry tissue in the second group and this difference was
      not statistically significant (p=0.521). The bursting pressure was determined as
      240.71 +/- 11.65 mmHg in the first group, 190.75 +/- 14.09 mmHg in the second
      group and the difference was statistically significant (p=0.002). The anastomotic
      resistances to intraluminal pressure were found statistically different whereas
      tissue hydroxyproline levels were normal between the groups. CONCLUSIONS: These
      results make us to consider mechanical differences occur related to the surgeons
      in the studies performed with the same technical detail.

PMID- 15244190
TI  - Jejunal perforation in mentally retarded patient due to an ingested chicken bone.
AB  - We report a mentally retarded case with jejunal perforation by ingested chicken
      bone. Foreign body ingestion constructs a health threat for mentally retarded
      people. Under guidance of the literature, travel of the bones in the
      gastrointestinal tract, diagnosis and treatment strategies are evaluated.

PMID- 15244191
TI  - Clinicopathologic features, cellular differentiation, PCNA and P53 expressions in
      gastrointestinal stromal tumors.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors are currently defined, as
      specific c-kit positive primary mesenchymal tumors of the gastrointestinal tract.
      Although increasing tumor size and mitotic activity favours aggressive behaviour,
      no specific histological criteria that enable the prediction of biological
      behaviour have yet been identified. The purpose of this study is, (1) to
      determine whether cell differentiation of gastrointestinal stromal tumors could
      be detected through their expression of various antigens, (2) to correlate their
      macroscopic and histologic features with cell differentiation, p53 expression,
      PCNA score and clinical outcome. METHODOLOGY: 65 gastrointestinal stromal tumors
      were included in this study. All cases were reviewed in terms of clinical
      presentation and courses. The cell morphology, growth pattern, cellularity,
      pleomorphism, mucosal invasion, necrosis and mitotic index were evaluated. Tissue
      sections were immunostained with CD117, CD34, alpha-smooth muscle actin, and S
      100 protein. PCNA score and p53 expressions were investigated to determine
      whether these could be used as prognostic indicator. RESULTS: Clinical outcome
      was obtained for 42 of the 65 patients. The follow-up time ranged from 1 to 240
      months (median: 20 months). The tumors occurred in 34 female and 31 male
      patients, ranging in age from 1.5 months to 80 years (median: 53 years). Tumors
      were located in the stomach (19), duodenum (10), jejunum and ileum (19), the
      colon (5), the anorectal region (5) and in the mesentery or omentum (7). 55
      tumors had spindle, 7 showed spindle and epithelioid, 3 had pure epithelioid
      morphology. Mitotic rate was found significantly different between probably
      benign 11 cases and recurrent 11 and metastatic 25 cases (p=0.001).
      Immunohistochemically, CD117 positivity was found 52 tumors (80%). 4 of 13 CD117
      negative tumors were positive for CD34. 4 of 9 tumors showing were also a-SMA and
      S-100 negative. CD34 positivity was determinated in 44 tumors (67.6%). alpha-SMA
      reactivity was seen in 39 tumors (60%). Only 5 tumors showed S-100 protein
      reactivity (7.69%). Statistically, mitotic rate was found significantly different
      between probably benign 11 cases and recurrent 11 and metastatic 14 cases
      (p=0.001). Furthermore, there were significant differences between the probably
      benign neoplasms and recurrent or metastatic cases in following parameters; p53
      expression, PCNA score, presence of necrosis and cellularity. CONCLUSIONS: GISTs
      could be specifically differentiated neoplasms and their some other aspects
      should be clarified such as relations with c-kit and other oncogenes and dual or
      "null" differentiation in the same neoplasm.

PMID- 15244192
TI  - Cystic mesenchymal hamartoma of the liver report of a case and review of the
      literature.
AB  - Mesenchymal Hamartoma (MH) of the liver constitutes the third or the fourth most
      common tumour of the liver in childhood and occurs most commonly in the first two
      years of life. It is often misdiagnosed clinically as a malignant tumour because
      of its rapid increase in size within a short period of time, or as a hepatic
      collections or abscess because of its cystic appearance. Although a benign
      lesion, MH may cause heart failure due to arteriovenous shunts, or death as a
      result of respiratory complications. A typical case of MH was recently
      encountered in a 6-years-old-boy. The patient presented with progres sive
      abdominal distension; surgery revealed a large mass arising from the right lobe
      of the liver. The mass was predominantly formed by fluid collections. Loose
      mesenchymal tissue and branched, tortuous bile ducts were the key diagnostic
      features. When predominantly cystic, MH may mimic lymphangioma both grossly and
      microscopically. Prudent examination of the cystic structures can establish a
      correct diagnosis.

PMID- 15244193
TI  - Retrorectal benign cystic teratoma misdiagnosed with high lying pararectal
      abscess.
AB  - A case of presacral teratoma with abscess formation is presented in this report.
      Teratomas, like the chordomas and dermoids, constitute the largest group of
      retrorectal tumors. Their presentation has varied. Dependent to unique
      localization, cystic teratoma complicated with abscess formation are misdiagnosed
      as high lying pararectal abscesses. Both diagnostic and therapeutic difficulties
      were evaluated with literature review.

PMID- 15244194
TI  - Jejunal intussusception caused by an inflammatory fibroid polyp.
AB  - The case of a 56-year old male with a jejunal intussusception due to the
      inflammatory fibroid polyp is presented. In the literature, eleven cases with
      jejunojejunal intussusception due to IFP were reported. This rare entitiy was
      reviewed with different perspectives in this report.

PMID- 15244195
TI  - Increased fasting serum levels of growth hormone and gastrin in patients with
      gastric and large bowel cancer.
AB  - BACKGROUND: Growth hormone (GH), Insulin-like growth factor-I (somatomedine, IGF
      I) and gastrin seem to play a significant role in cell proliferation in mammalian
      and rat cells. The role of these factors in the etiology of gastric and large
      bowel cancer has not been completely elucidated. The aim of this study was to
      concurrently estimate the levels of GH, IGF-I and gastrin in a group of patients
      with gastric and colorectal cancer and to compare the results with those of a
      group of normal controls. PATIENTS AND METHODS: In 33 consecutive patients with
      gastric (16 patients) and large bowel (17 patients) cancer, the serum levels of
      GH, IGF-I and gastrin were measured by radioimmunoassay. Fifty-four normal people
      were served as controls. RESULTS: Significantly higher levels of serum GH (3.16
      +/- 3.12 ng/ml in gastric cancer patients vs. 3.01 +/- 2.91 ng/ml in colorectal
      cancer patients vs. 0.69 +/- 1.60 ng/ml in normal controls, adjusted P<0.001) and
      gastrin (98.2 +/- 87.9 pg/ml in gastric cancer patients vs. 95.3 +/- 85.4 pg/ml
      in colorectal cancer patients, vs. 47.5 +/- 32.4 pg/ml in normal controls,
      adjusted P<0.035 and <0.05 respectively) were found in both groups of patients
      compared with normal controls. The levels of IGF-I in patients with gastric and
      colorectal cancer although higher compared to normal controls did not reach
      statistical significance. (98.2 +/- 87.9 pg/ml vs. 95.3 +/- 85.4 vs. 47.5 +/-
      32.4 respectively) (adjusted P=0.070). CONCLUSION: It is concluded that in
      patients with gastric and colorectal cancer a significant increase of serum GH
      and gastrin can be found. This increase is likely to play a role in gastric and
      colorectal carcinogenesis.

PMID- 15244196
TI  - Lamivudine induced stable reversal in HBV liver cirrhosis Child C: a case report.
AB  - A 40-year-old viremic woman with HBV related liver cirrhosis (Child-Plugh - C)
      received 100 mg lamivudine daily for 24 months. Initially the patient was with
      hepato-splenomegaly, marked ascites and mild jaundice. There were no signs of
      portal encephalopaty and gastrointestinal haemorrhage. The baseline ALT was about
      6 times above the upper limit of normal. Hypoalbuminemia of 29 g/l as well as
      hyperbilirubinemia of 40 mmol/L and decreased protrombin index of 47% was found.
      Serological tests showed positive serum HBsAg and anti-HBe antibodies. The
      patient was HBeAg negative, but with detectable serum HBV DNA (500 pg/mL) by dot
      blot hybridization HDV, HCV and HIV co-infections were excluded. A marked
      improvement in liver function had been found at the end of the third month of
      therapy, with normalization of bilirubin and ALT activity. Serum albumin and
      protrombine index increased from 29 g/l to 36 g/l and from 47% to 92%,
      respectively. The patient was without ascites and Child-Plough score decreased
      from 10 to 5 points. Serum HBV DNA rapidly decreased at the end of first
      treatment month and was undetectable three months after the initiation of
      lamivudine therapy. We found two viremic episodes during the lamivudine
      treatment. However, Child-Pugh score did not increased and the patient remained
      with compensated liver disease and with lower ALT than baseline value. The main
      question is haw long such patients have to receive the lamivudine treatment.

PMID- 15244197
TI  - Role of endoscopy in the diagnosis of aneurysm-duodenal fistula.
AB  - BACKGROUND: Aneurysms complicated by enteric fistulae are uniformly fatal
      clinical conditions and therefore should be placed high on the list of possible
      diagnoses in any patient with aneurysmal disease and gastrointestinal bleeding. A
      number of different diagnostic techniques have been proposed, but most of them
      are usually of little help or even misleading. METHODOLOGY: Between May 2000 and
      April 2002, endoscopy was performed in 290 consecutive patients with upper
      gastrointestinal bleeding. We retrospectively evaluated that endoscopy may
      provide an important diagnostic clue in aneurysm-enteric fistulae. RESULTS: Three
      patients with gastrointestinal bleeding presented with aneurysmal disease
      complicated by duodenal fistula formation. Two patients presented with
      aortoduodenal fistula, and the last one hepatic artery aneurysm with duodenal
      fistula formation. In all of our cases, endoscopic findings were suggestive and
      helpful for the preoperative diagnosis. CONCLUSIONS: Considering that prompt
      aggressive surgical intervention is mandatory for survival and more than 90% of
      aneurysmal disease with duodenal fistula formation should be within range of the
      endoscopists, aggressive and thorough endoscopy with a high index of clinical
      suspicion seems to be the most important diagnostic test in these difficult
      cases.

PMID- 15244198
TI  - The role of serum leptin levels in chronic hepatitis C with steatosis.
AB  - BACKGROUND/AIMS: Leptin has recently been suggested to play a role in the
      pathogenesis of hepatic steatosis and steatohepatitis in the absence of viral
      infection. The aim of this study was to evaluate whether leptin levels are
      associated with hepatic steatosis in chronic hepatitis C. METHODOLOGY: Thirty-one
      patients (22 female, 9 male, mean age: 51 +/- 9) with histologically proven
      chronic hepatitis C were included in this prospective, controlled, observational,
      clinical study with blind outcome assessment. Patients with and without steatosis
      in liver biopsy served as each others' controls. RESULTS: Chronic hepatitis C
      patients with (n=23) and without steatosis (n=8) were similar with respect to
      their serum glucose, lipid and leptin levels (p>0.05). Serum leptin levels were
      correlated with both patient factors, such as obesity and with liver enzymes,
      such as ALT, AST only in patients with steatosis. Chronic hepatitis C patients
      with or without steatosis had similar leptin levels of 6.3 +/- 2.5 and 4.9 +/-
      2.5, respectively. CONCLUSION: Leptin levels were well correlated with
      antropometrical parameters in chronic hepatitis C patients. Leptin levels were
      associated with evidence of impaired hepatic function in patients with chronic
      HCV related steatosis. Serum leptin may be a prognostic marker for patients with
      chronic HCV infection with steatosis.

PMID- 15244199
TI  - Serum paraoxonase levels in gastric cancer.
AB  - BACKGROUND/AIMS: Serum paraoxonase (PON) is a calcium-dependent esterase that is
      known to contribute to the antioxidant protection conferred by high-density
      lipoprotein (HDL) on low-density lipoprotein (LDL) oxidation. Serum PON activity
      was shown to be reduced in patients with diseases such as myocardial infarction,
      diabetes mellitus, etc in comparison to healthy subjects. However, the relation
      of serum PON levels to cancer is still not known. So, we intended to measure
      serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to
      investigate the relation of serum PON to plasma lipoproteins in the patients with
      gastric cancer. METHODOLOGY: We measured serum PON, HDL, LDL and VLDL levels in
      20 patients with gastric cancer and in 20 age-and gender-matched healthy
      controls. We investigated the relationship between PON and HDL, PON and LDL, and
      PON and VLDL. RESULTS: Serum HDL levels were lower in the patients than in
      controls (33.10 +/- 7.75 mg/dL, and 47.30 +/- 6.65 mg/dL, respectively)
      (p<0.0001). Serum VLDL levels were lower in the patients than in controls (21.65
      +/- 6.92 mg/dL, and 33.10 +/- 6.09 mg/dL, respectively) (p<0.0001). Serum LDL
      levels measured in the patients were not significantly different from those of
      the controls. Serum PON levels were lower in the patients than in controls (67.10
      +/- 17.92 U/L, and 87.50 +/- 23.39 U/L, respectively) and there was a positive
      correlation between serum PON and HDL levels (r: 0.52, p<0.05). CONCLUSIONS: We
      concluded that the patients with gastric cancer had low serum PON, HDL, and VLDL
      levels compared to healthy controls. The importance of PON as a predictive risk
      factor for cancer should be assessed in future studies.

PMID- 15244200
TI  - The release of insulin in fatty liver.
AB  - AIMS: To evaluate the blood levels of lipids, insulin resistance and the release
      of insulin in the patients with fatty liver. METHODOLOGY: Ninety one patients
      with fatty liver and forty seven healthy subjects were included in the study. The
      diagnosis of fatty liver was established by measuring blood levels of lipids and
      measuring liver echogenity by ultrasound. Fasting plasma levels of lipids,
      glucose and insulin were measured in the patient group and control group, and the
      rate of insulin resistance was calculated. HOMA test was used to calculate the
      insulin resistance. INSULIN RESISTANCE: Fasting insulin value (microU/mL) x
      Fasting blood glucose value (mmol/L)/22.5 Liver echogenity was measured by a 3.75
      mHz ultrasound probe and was graded by comparison with renal cortical paranchymal
      echogenity in both groups. Increased blood levels of lipids and increased liver
      echogenity on the ultrasonography were accepted as fatty liver. Liver biopsy was
      not applied. The patients with liver and/or renal paranchymal disease were
      excluded from the study. The rate of release of insulin was calculated according
      to the following formula. 20 x plasma levels of insulin (mIU/mL)/plasma levels of
      glucose (mmol/L)-3.5 RESULTS: In the fatty liver group, plasma levels of
      cholesterol were 253.5 +/- 41.0 (161-440) mg/dL, plasma levels of triglycerides
      were 231.8 +/- 74.4 (45-493) mg/dL, grading of liver echogenity was 1.9 +/- 0.6
      (1-3), the rate of release of insulin was 111.5 +/- 82.2 (3-463.8) and the rate
      of insulin resistance was 22.4 +/- 4.1 (18.3-26.5). In the control group, plasma
      levels of cholesterol were 173.4 +/- 19.1 (122-207) mg/dL, plasma levels of
      triglycerides were 110.5 +/- 39.3 (40-185) mg/dL, grading of liver echogenity was
      1.0 +/- 0.1 (1-1), the rate of release of insulin was 129.6 +/- 84.1 (14.5-360)
      and the rate of insulin resistance was 20.3 +/- 2.1 (18.2-22.4). The rate of
      release of insulin and insulin resistance were similar in both groups (p>0.5).
      CONCLUSIONS: We observed that the rate of release of insulin in the patients with
      fatty liver was not different from that of the healthy subjects.

PMID- 15244201
TI  - The presence of the antigliadin antibodies in autoimmune thyroid diseases.
AB  - AIMS: To investigate the presence of the antigliadin antibodies in the patients
      with Graves' disease and Hashimoto's thyroiditis. METHODOLOGY: Four hundred
      patients with autoimmune thyroid disease (280 Graves' disease and 120 Hashimoto's
      thyroiditis ) were included in the study. The patients with celiac sprue patients
      were excluded. For the diagnosis of autoimmune thyroiditis, blood levels of
      thyrotropin (TSH), free thyroxine (FT4), and the titration of thyroid
      autoantibodies (TgAb and TmAb) were measured, and the thyroid gland was
      ultrasonographycally evaluated. After the diagnosis of autoimmune thyroid disease
      was established, the titration of antigliadin antibodies (Ig A and B) were
      routinely detected. RESULTS: Twenty two patients (5.5 per cent) with autoimmune
      thyroiditis had positive antigliadin antibodies. Polyglandular endocrine syndrome
      was diagnosed in most of these patients. CONCLUSIONS: We claim that polyglandular
      endocrine syndrome is the commonest cause of positivity of antigliadin antibodies
      in the patients with autoimmune thyroid disease.

PMID- 15244202
TI  - Liver function tests during antithyroid therapy in hyperthyroidism.
AB  - AIMS: To investigate the liver function tests during antithyroid treatment in the
      patients with hyperthyroidism. METHODOLOGY: Four hundred sixty five patients with
      hyperthyroidism (285 Graves' disease and 180 toxic nodular/multinodular goiter)
      and fifty healthy subjects were included in the study. The patients who had
      abnormal liver function tests were excluded from the study. Blood levels of
      thyrotropin (TSH), free thyroxine (FT4), alanine transaminase (ALT) and aspartate
      transaminase (AST) were detected at the beginning of the treatment (basal
      levels), and at the third and sixth months of the treatment. The patients were
      treated with propylthiouracil (PTU). RESULTS: Average of age was 40.1 +/- 5.8
      years in the patient group and was 37.3 +/- 4.5 years in the control group. TSH,
      FT4, ALT and AST levels measured in the patient and control group are shown in
      Table 1. Basal levels of TSH were lower in the study group than in the control
      group (p<0.001), and basal levels of FT4 were higher in the study group than in
      the control group (p<0.001). Basal levels of ALT and AST, and the levels of TSH,
      FT4, ALT and AST measured at the third and sixth months were similar in both
      groups. CONCLUSIONS: We did not find abnormal liver function tests during the
      antithyroid treatment in the patients with hyperthyroidism.

PMID- 15244203
TI  - Remifentanil/midazolam versus tramadol/midazolam use for colonoscopy.
AB  - One of the most commonly performed outpatient procedure is colonoscopy. The pain
      and anxiety is frequently associated with colonoscopy. The aim of this study was
      to compare the effectiveness of remifentanil/midazolam, and tramadol/midazolam
      for iv sedation and analgesia during colonoscopy. Twentysix patients (age range
      18-65 years) scheduled for ambulatory colonoscopy were included to study. All
      patients received midazolam 1 mg intravenous. After two minutes in Group R
      (remifentanil/midazolam, n=18) remifentanil bolus (10 microg) and infusion 0.03
      microg kg(-1) min(-1) were administered until adequate sedation level was
      achieved. In Group T (tramadol/midazolam, n=18) iv tramadol 50 mg was given
      concurrently. During procedure 2 L/min oxygen was supplemented via face mask to
      all patients. Haemodynamic variables, respiratory depression, level of sedation,
      postoperative recovery, patient and gastroenterologist satisfaction were
      surveyed. Patients were asked to verbally rate their level of pain, on an 10
      point numerical rating scale (1=no pain, 10=severe pain). Chi-square, student t
      test, and mann whitney U test were used for statistical analysis. Colonoscopy was
      carried out successfully in all patients. There were no episodes of desaturation
      or airway compromise. Haemodynamic parameters were similar in both groups.
      Sistolic arterial and diastolic arterial pressures were increased at 10 and 15
      minutes in all patients (P<0.05). There were no significant changes in heart rate
      in both groups. The level of sedation in group R was higher than group T during
      colonoscopy. The patients in group T had higher pain scores. Gastroenterologist
      satisfaction and patient satisfaction were similar in both groups. Our results
      suggests that, sedoanalgesia with midazolam/remifentanil may be an alternative to
      sedoanalgesia with midazolam/tramadol for colonoscopy.

PMID- 15244204
TI  - Crohn's disease; analysis of 105 patients.
AB  - In this paper, 105 patients with Crohn's disease, (47 M, 58 F), mean age 37.4 +/-
      42 years were evaluated clinically, demographically and epidemiologically. Mean
      age of patients at the time of diagnosis was 26.5 +/- 10.9 years. Follow-up
      period was 2.7 +/- 2.1 years on average. On admission, symptoms or signs were as
      follows: right lower quadrant pain 90.5%, abdominal mass 18.1%, enterocutaneous
      fistula 11.4% and subileus 9.5%. Diagnosis of Crohn's disease was established
      during appendectomy in 14 patients (13.3%). Family history of inflammatory bowel
      disease was determined only in six patients (5.7%). Intestinal localization were
      as follows: ileo colonic 52%, ileal 38%, colonic 10%. Clinical forms were
      inflammatory (68%), fistulous (23%) and obstructive (9%). Sacroiliitis (7.6%),
      ankylosing spondylitis (4.7%), erythema nodosum (2.9%), pyoderma gangrenosum (1%)
      were detected as extraintestinal manifestations. Of the patients, 12.4% underwent
      surgical intervention due to abscess drainage in 6.6%, fistulectomy in 3.8%,
      stricture resection in 1.9%. Medical therapy alone was sufficient in 75.3% of
      patients. As a result, our cases mentioned in this paper reflect the general
      characteristics of Crohn's disease and prominence of regular visits and
      treatment.

PMID- 15244205
TI  - Dual infection in chronic hepatitis C patients.
AB  - Hepatitis C and B virus(HCV, HBV) dual infection may occur and even persist in
      the same patient. Different results have been found in clinical and laboratory
      studies of dually infected patients. AIM: In our study, we aimed to investigate
      the effect of previous or present hepatitis B virus infection to clinical course
      and antiviral therapy in patients with chronic hepatitis C. METHOD: Hundredthirty
      consecutive patients with hepatitis C, who were referred to our gastroenterology
      unit, were studied retrospectively. Patients who were exposed to HBV infection
      were named as group 1, and patients who had pure hepatitis C infection were named
      as group 2. Fifty patients in group 1 were compared with 80 patients in group 2.
      HBs Ag was positive in 12, and HBV antibodies were positive in the other 38
      patients of group 1. RESULTS: Age, sex, follow-up duration, transaminase levels,
      liver synthesis functions, histopathological findings, Child-Pugh stages and
      presence of complications were not statistically different in groups 1 and 2. HBV
      DNA by PCR assay was negative in all 12 HBs Ag positive patients. Hepatocelluler
      carcinoma(HCC) was found totally in 8 cases, 2 in group 1 and 6 in group 2, while
      none in HBs Ag positive patients. Antiviral therapy was administired to 39
      patients, 15 in group 1 and 24 in group 2. There was no difference in regard to
      treatment duration and response to treatment between both groups. CONCLUSION: In
      our study, we have found previous or present HBV infections were observed
      frequently in chronic hepatitis C patients, although it's effect to clinical
      course and antiviral therapy is not significant.

PMID- 15244206
TI  - Lamivudine treatment in patients with hepatitis B virus induced liver cirrhosis.
AB  - BACKGROUND/AIMS: First studies have suggested a beneficial effect of lamivudine
      in patients with cirrhosis caused by replicating hepatitis B virus. Whether long
      term lamivudine therapy is effective in HBV-related liver cirrhosis patients was
      prospectively evaluated. METHODS: Thirty-one patients with hepatitis B virus
      related compensated/decompensated cirrhosis, all with quantitative DNA +ve by
      hybridization (10 HBeAg +ve, 21 anti-HBe +ve), received lamivudine 100 mg/day for
      average 16.3 (4-34) months. RESULTS: At the end of therapy HBeAg seroconversion
      was observed in one patient. HBV DNA lost in all patients except two. Albumin
      levels increased (p<0.05). ALT levels and Child-Pugh-Turcotte scores decreased
      (p<0.05). Any complication related with liver cirrhosis was not observed during
      treatment period despite spontaneous ascitic infection in one and hepatic coma in
      two were occurred before therapy. Only one patient had clinical breakthrough
      presented by increase in ALT levels and reappearing of HBV DNA during therapy.
      CONCLUSION: In patients with cirrhosis caused by replicating hepatitis B virus,
      prolonged therapy with lamivudine is well tolerated and resulted in improved
      serum biochemical values and loss of HBV DNA. Clinical improvements may also
      occur.

PMID- 15244207
TI  - Cyclosporin for severe ulcerative colitis attacks.
AB  - BACKGROUND/AIMS: Cyclosporin-A is used as alternative medical therapy in steroid
      refractory ulcerative colitis with severe activity. In spite of known
      effectivity, the long term results of cyclosporin-A therapy is not clear for
      today. METHODS: The results of 13 steroid refractory patients that treated with
      cyclosporin-A were retrospectively assessed. Cyclosporin-A was started as orally,
      8 mg/kg/day in 4 patients and intravenously, 4 mg/kg/day in 9 patients.
      Intravenous therapy changed to oral therapy one week after beginning. Patients
      also received 5-ASA and azathioprine. Steroid was tapered. RESULTS: Ten patients
      responded to treatment in a mean of 9 days (range: 2-30 days). Three unresponded
      patients underwent total colectomy on 7, 11 and 19th day of therapy. Ten
      initially responded patients received the drug for average 4.9 months. Of these,
      four relapsed during and one relapsed soon after therapy. Four of 5 relapser
      patients underwent colectomy. One patient that not accepted surgical intervention
      is still receiving medical therapy. Remaining 5 patients, 38% of total group; 50%
      of patients that initially responded, maintain the remission at the end of
      average 17 months of follow up period. CONCLUSION: Cyclosporin-A therapy in
      severe ulcerative colitis that is refractory to steroids, provides initial
      remission in 80% of patients and allows 40% to retain their colon for 1 year.

PMID- 15244208
TI  - The effect of pneumatic balloon dilatation on gastric emptying in patients with
      achalasia.
AB  - Achalasia is a disease that characterized by relaxation hazard of lower
      esophageal sphincter. In patients with achalasia, it's known that gastric
      emptying time is delayed. In this study we aimed to evaluate the difference
      between the gastric emptying time before and after pneumatic balloon dilatation.
      Nine achalasia patients (7 female, mean age 51.5 +/- 13.1, range 36-71 year) that
      were diagnosed as clinically, radiologically and manometrically were enrolled
      into the study. In all patients, before and after pneumatic dilatation, gastric
      emptying time was measured with radionuclide method after eating a solid meal. In
      severely effected patients labeled egg was passed to stomach by a nasogastric
      tube. One hour after observing initial gastric activity, irradiation was detected
      dynamically. Radionuclide emptying time before (T1/2) dilatation was a mean of
      301.9 +/- 64.7, and after dilatation 221.7 +/- 370.8 minute (p=0.018). As a
      result, elongation in gastric emptying time in patients with achalasia
      significantly decreases after effective pneumatic balloon dilatation.

PMID- 15244209
TI  - Terlipressin and albumin combination treatment in hepatorenal syndrome.
AB  - OBJECTIVES: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis,
      leading to death in nearly all of cases in the absence of liver transplantation.
      Several treatments have been attempted as a bridge to liver transplantation.
      Promising results have been shown with terlipressin and albumin treatment. The
      aim of this retrospective study was to evaluate our patients with HRS and the
      effects of combined therapy of terlipressin and albumin on survival. PATIENTS AND
      METHODS: Twenty two patients (15 with type 1 HRS and 7 with type 2 HRS) who were
      admitted to our clinic between 1996 and 2001, were enrolled. All 7 pts with type
      1 HRS were given terlipressin 2-4 mg/day and albumin 2 x 20 g/day for 6 days
      (range: 3-14). RESULTS: Rate of mortality in hospital was 64% in total group, 80%
      in type 1 and 29% in type 2. Additionally rate of death was 57% in type 1
      patients that received terlipressin+albumin and 100% in unreceived ones (p<0.05).
      CONCLUSION: In this retrospective study, survival following improvement in renal
      function was noted in nearly half (43%) of type 1 patients that received
      terlipressin+albumin. Parameters associated with response to terlipressin+albumin
      and increased survival should be defined better in a large cohort of cirrhotic
      patients with HRS.

PMID- 15244210
TI  - In treatment of active duodenal ulcer and Helicobacter pylori eradication.
AB  - AIM: To compare the efficacy of lansoprazole and pantoprazole in treatment of
      active duodenal ulcer and Helicobacterpylori eradication. METHODOLOGY: A total of
      50 patients, with a positive rapid urease test and endoscopically diagnosed
      active duodenal ulcer, were randomly assigned to one of two treatment groups
      after endoscopic examinations. Patients in the first group received lansoprazole
      30 mg b.d., amoxycillin 1000mg b.d., clarithromycin 500 mg b.d.; patients in the
      second group received pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d.,
      clarithromycin 500 mg b.d for two weeks. Patients were scheduled for repeat
      endoscopic examination; repeat rapid urease test, and histological examination 4
      weeks after the end of the therapy. RESULTS: Hp was eradicated in 84.2% of the
      patients received lansoprazole and in 83.3% of the patients received
      pantoprazole. The difference was not significant (P>0.05). In the lansoprazole
      group 90.5%, and in the pantoprazole group 83.3% of the patients experienced
      complete duodenal ulcer healing at the time of follow-up endoscopic examination.
      We found no statistical significant difference between the two groups.
      CONCLUSION: Lansoprazole and pantoprazole both have similar effect in eradication
      of Hp, and in terms of ulcer healing. Comparative studies in larger trials are
      needed to compare the efficacy of lansoprazole and pantoprazole in treatment of
      active duodenal ulcers.

PMID- 15244211
TI  - Long-lasting reflux episodes in gastroesophageal reflux and its complications in
      children.
AB  - BACKGROUND/AIMS: The aim of the study was to test the hypothesis that long
      lasting reflux episodes (episodes longer than 5 minutes and longest reflux
      episode) are more and are longer in patients with complicated gastroesophageal
      reflux (GER), such as reflux esophagitis, etc. MATERIAL AND METHODS: In a
      prospective study 120 children (age 2 months to 14 years) were evaluated for the
      presence of GER and its complications (respiratory disease, reflux esophagitis).
      Out of them 51 were without GER (control group). With functional GER were 17,
      respiratory disease and GER had 21, and RE 16. Diagnosis of GER was established
      by computed 24 hour pH monitoring (C24hpHM) using Digitrapper Mark III,
      Synectics, Sweden. GER was positive if pH<4 was >5% of investigated time. Number
      of reflux episodes (NRE), episodes longer than 5 minutes (EL5), the longest
      reflux episodes (LRE), reflux index (RI) and duration of investigation were
      considered for the purpuse of this study. RESULTS: There was no significant
      statistical difference for the duration of procedure between the groups (Kruskal
      Wallis test p>0.05). There was significant statistical difference for all
      parameters between control group and group with RE (Kruskal-Wallis test p<0.05).
      In RE patients there was significantly higher number of EL5, and longer duration
      of LRE compared with uncomplicated GER, functional GER, and GER with respiratory
      disease (Kruskal-Wallis test p<0.05). Between respiratory disese and functional
      GER there was no significant statistical difference. There was significant
      statistical difference between mild and severe RE for EL5 and LRE (Kruskal-Wallis
      test p<0.05). CONCLUSION: We confirmed that long lasting reflux episodes (EL5,
      LRE) are significantly higher in number and longer duration in children with RE,
      and together with acid reflux area, and impaired esophageal clearance contribute
      to development of RE.

PMID- 15244212
TI  - Malignancy risk of gastric ulcers: could it be higher than the expected values?
AB  - There are many reported methods in the literature for the discrimination between
      malignant and benign gastric ulcers by endoscopic evaluation, but unfortunately
      this could not be done in 20% of the cases. The sensitivity for diagnosis of
      malignant ulcers increases by multiple biopsies and endoscopies. In this study,
      solitary gastric ulcers which were detected at 1680 gastroscopies between January
      2001 and June 2002 are evaluated. The ulcers which were on gastric mass, multiple
      little aphthous ulcers and ulcers with hemorrhagic erosions having a diameter
      less than 0.5 cm are excluded from the study. There were a total of 32 patients,
      20 males and 10 females, having a median age of 54.8 years. In the initial
      biopsy, only nine patients had malignancy results. The 23 cases having benign
      results had medical treatment with proton pump inhibitors for four weeks. At the
      end of this period, they had their second gastroscopic evaluation. The ulcers of
      14 patients did not heal and second round biopsies were per formed. Additionally
      four cases had malignant results following the second round biopsy. After 4 weeks
      the remaining 10 cases had their third round of gastroscopy which revealed that
      two patients still had the ulcer. A third round biopsy was done and one case had
      a malignancy result. A total of 14 malignancy cases was encountered, and nine of
      them was adenocarcinoma, four were signet cell carcinoma and one case was MALT
      lymphoma. 78% of the malignant cases were encountered at the proximal site of the
      incisura angularis, and in 64% of these malignant cases nodular lesions around
      the ulcer were encountered. The four ulcers out of eight which were settled at
      the smaller curvature site were malignant, and only one ulcer at cardia was also
      malignant. The main method for the discrimination of malign-benign ulcer is still
      biopsy. The follow up of the patients with repeated multiple biopsies may
      increase the sensitivity for diagnosis of malignancies in the solitary gastric
      ulcer.

PMID- 15244213
TI  - Serum gastrin levels in patients with inflammatory bowel disease.
AB  - The aim of this study was to estimate the levels of serum gastrin in a group of
      patients with either ulcerative colitis or Crohn's disease and to compare the
      results with those of a group of normal controls. In 108 consecutive patients
      with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with
      indetermined colitis) serum levels of gastrin were measured by radioimmunoassay.
      One hundred and eight normal people were served as controls. The levels of serum
      gastrin were significantly elevated in patients with Crohn's disease compared to
      normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05),
      irrespectively of the activity of the disease. On the contrary, patients with
      ulcerative colitis exhibited no significant differences compared to normal
      controls. Differences between Crohn's disease and ulcerative colitis patients
      were statistically significant (P<0.001). The rate of infection by Helicobacter
      pylori in patients with inflammatory bowel disease was statistically
      significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001).
      It is concluded that patients with active or inactive Crohn's disease have
      increased levels of serum gastrin. This may have implications concerning the high
      incidence of upper GI lesions found in patients with Crohn's disease despite the
      very low incidence of Helicobacter pylori infection.

PMID- 15244214
TI  - Relation between Helicobacter pylori infection, thyroid hormone levels and
      cardiovascular risk factors on blood donors.
AB  - The aim of this study was to assess the relationship between Helicobacter pylori
      (Hp) infection, serum thyroid hormone levels and certain cardiovascular risk
      factors in normal volunteers. In 110 blood donors (85 men, 25 women, aged 35.6 +/
      9.76) the serum levels of IgG antibodies against Hp were estimated using a
      sensitive immunoassay. Serum estimation of T3, T4, TSH, FT3, FT4, thyroid
      (microsomial) autoantibodies, C-Reactive-Protein, a1-acid-glycoprotein, vitamin
      B12, folic acid, cholesterol, triglycerides, total lipids, HDL, LDL, and
      antibodies against hepatitis A, was also carried-out. In all subjects a number of
      clinicoepidemiological parameters including body mass index, smoking habits,
      educational level, number of siblings and presence of symptoms from the digestive
      system were carefully recorded. Statistical analyses were performed using the
      SPSS statistical package. Helicobacter pylori infection was found in 54 subjects
      (49.1%). On univariate analysis, significant differences between subjects
      positive and negative for Helicobacter pylori infection were found for FreeT3
      (3.11 +/- 0.5 pmol/ vs. 3.42 +/- 0.8 pmol/l, P=0.025), FreeT4 (1.04 +/- 0.2 ng/dl
      vs. 1.17 +/- 0.3 ng/dl, P=0.025), and thyroid autoanti bodies (23.65 +/- 24 vs.
      14.97 +/- 8, P=0.018). Significant differences were also found for Cholesterol
      (207.8 +/- 39 mg/dl vs. 193.3 +/- 40 md/dl, P=0.05), LDL (133.2 +/- 32 mg/dl vs.
      119.6 +/- 40 mg/dl, P=0.05) and folic acid (7.66 +/- 3.7 ng/ml vs. 6.39 +/- 2.5
      ng/ml, P=0.038). A significantly positive correlation of Hp infection with age
      and number of siblings and a negative one with educational level were noticed. No
      differences concerning the levels of acute phase proteins, vitamin B12,
      antibodies against hepatitis A, body mass index, and smoking habits were found.
      On logistic regression analysis, significant differences remained only for
      thyroid autoantibodies (Odds ratio for titer ?30: 7.8, P=0.012), age (Odds Ratio
      for those aged >40 years vs those aged <40 years: 3.8, P=0.022) and educational
      level (Odds ratio for elementary 8.7 and moderate 5.1 vs higher education,
      P=0.003 and P=0.011 respectively). It is concluded that a relationship exist
      between Hp infection and the presence of high titers of thyroid autoantibodies in
      blood donors. There are no indications of the existence of a relationship between
      Hp infection with thyroid hormone levels, lipid concentrations and other
      cardiovascular risk factors.

PMID- 15244215
TI  - Early protein intakes and adiposity: reloaded or downloaded?
AB  - It has been hypothesized that feeding human milk through the first year of life
      may have a protective effect towards a later adiposity development, in contrast
      with formula feeding. The low protein content of human milk has been hypothesized
      as a plausible biological hypothesis. Regardless, it is often underscored that
      feeding human milk is associated with a higher rate of weight gain in the first
      two months of life. CONCLUSION: In our opinion, it seems that the protective
      effect of human milk, if any, on adiposity development is far more complex, and
      tightly bound to the peculiarity of human milk composition and breastfeeding
      practice.

PMID- 15244216
TI  - Calculation of resting energy expenditure in obese children.
AB  - For the calculation of resting energy expenditure, which is the main part of
      total energy expenditure in children with low physical activity, Fusch et al.
      have developed an equation. CONCLUSION: This equation might be useful for
      research but not in daily work with obese patients.

PMID- 15244217
TI  - Increased QT dispersion in breath-holding spells.
AB  - Breath-holding spells (BHS) in children can be a frightening and clinically
      challenging paroxysmal, non-epileptic childhood disorder. The pathophysiology has
      been found to incorporate central nervous system dysregulation in addition to an
      underlying genetic predisposition. Akalin and colleagues found group differences
      (BHS versus controls) in QT dispersion and QTc dispersion. These differences,
      however, may have been affected mainly by normal sinus arrhythmia from the
      predominant cyanotic BHS cohort. CONCLUSION: The subtle differences measured in
      the current study between pallid and cyanotic breath-holder groups, in terms of
      increased QTc dispersion in the pallid group, may represent an additional factor
      impacted upon by the resting state of underlying central autonomic dysregulation.

PMID- 15244218
TI  - Monitoring of IgE-mediated food allergy in childhood.
AB  - Testing for IgE-mediated allergy is performed to reach or refute a suspected
      allergy. But a positive test does only indicate sensitization and not necessarily
      clinical allergy. A diagnostic challenge procedure is therefore necessary. Also,
      in the phase of tolerance development a challenge is needed as clinical tolerance
      is reached before allergen-specific IgE antibodies have disappeared. During
      recent years, an increasing interest has been given to the possibility of using
      the concentration of specific IgE and the size of the skin prick test wheal to
      tell the optimal time to do a challenge without exposing the child to a risk of a
      severe reaction. CONCLUSION: Algorithms on when to do and when not to do a food
      challenge may be useful but should be used with great caution. Reasonable
      consideration should be paid to the severity of previous reactions and the kind
      of allergen involved.

PMID- 15244219
TI  - Neural maturation of breastfed and formula-fed infants.
AB  - BACKGROUND: Human milk provides infants with a full complement of all
      polyunsaturated fatty acids, including docosahexaenoic acid (DHA) and arachidonic
      acid (AA). Formula milks only contain the precursors of DHA, AA and linoleic
      acid, and hence formula-fed infants must synthesize their own DHA and AA. AIM: To
      evaluate the effect of feeding--whether breastfeeding or formula-feeding--in
      early infancy upon subsequent neurodevelopment and achievement of optimum brain
      function. SUBJECTS AND METHODS: The study included 53 normal, healthy infants (30
      exclusively breastfed infants and 23 exclusively formula-fed infants) at the age
      of 1 y (+/-1 mo). Each infant was subjected to a full physical and neurological
      examination together with neurophysiological studies including flash visual
      evoked potential (FVEP), brainstem auditory evoked potential (BAEP) and
      somatosensory evoked potential (SSEP). RESULTS: There was significant
      prolongation of P100 wave latency of FVEP in formula-fed infants, together with
      significant prolongation of absolute latency of waves I, III and V of BAEP in
      formula-fed infants compared with breastfed infants. There was significant
      prolongation in inter-peak latencies between cortical and Erb's components in
      formula-fed infants compared with breastfed infants. CONCLUSION: We can conclude
      that VEP, BAEP and SSEP are more mature in breastfed infants relative to formula
      fed infants at 1 y of age, and thus breast milk helps earlier development and
      maturation of some aspects of the nervous system than milk formulas.

PMID- 15244220
TI  - Resting energy expenditure in obese children aged 4 to 15 years: measured versus
      predicted data.
AB  - AIM: To measure the relationship of resting energy expenditure (REE) and body
      composition, and to compare REE data calculated from anthropometric parameters
      using published equations with measurements obtained by indirect calorimetry (IC)
      in a population of obese paediatric patients. METHODS: The study included 82
      healthy obese paediatric subjects (49 boys, 33 girls; body mass index 29.6 +/-
      5.0 kg/m , age 1 1.4 +/- 2.6 y, weight 72.4 +/- 20.9 kg, height 155 +/- 14 cm).
      REE was measured by IC, body composition was determined by dual energy X-ray
      absorptiometry (DXA). Bootstrap analysis was performed to validate the step-down
      linear regression analysis results. RESULTS: Lean body mass (LBM) and weight were
      identified as the most significant determinants of REE. LBM was the best single
      predictor (r = 0.78; p < 0.001) for REE. Regression equations are given in the
      text. Prediction of REE on the basis of published anthropometric formulas was
      strongly dependent from the equation used. Some equations tend to underestimate
      REE in the population studied with a considerable systematic error. CONCLUSION:
      In the present paper we show that (1) the published equations to predict REE in
      obese subjects yield scattered data and some are even biased by a systematic
      error, and that (2) the inclusion of DXA-derived LBM improves accuracy and
      precision of predicted REE in boys and girls aged from 4 to 10 y and in boys from
      11 to 15 y.

PMID- 15244221
TI  - Bone mass evaluated by calcaneous ultrasound and radial peripheral computed
      tomography in 726 youngsters.
AB  - AIM: To compare the results of ultrasound and computed peripheral tomography in
      evaluating bone mass in a population of normal children. METHODS: Seven hundred
      and twenty-six healthy school children (260 males; age 8.3-20.9 y) underwent
      calcaneous ultrasound and peripheral computed tomography at the ultradistal
      radius. Broadband ultrasound attenuation (BUA) and areal and volumetric bone
      mineral density (aBMD and vBMD) were evaluated. The results were compared and
      correlated among them and with auxological parameters (height, BMI and pubertal
      stages) using the software package SPSS for Windows. RESULTS: The three variables
      examined (BUA, aBMD and vBMD) all showed a progressive increase with age and a
      positive correlation with age, height and BMI. When the population was subdivided
      according to pubertal stages, all variables showed a progressive increase, the
      difference being significant when stages 1-2 were compared with stages 4-5. A
      significant correlation was present among BUA, aBMD and vBMD even if the Pearson
      correlation coefficient was not high. CONCLUSIONS: The similar pattern of BUA,
      aBMD and vBMD with respect to age, height and pubertal stages indicates that
      ultrasound could be a reliable method to screen bone mass abnormalities in
      children. The low correlation coefficient, however, suggests that the methods
      employed measure different bone parameters. Moreover, the different skeletal
      locations could also account for these results.

PMID- 15244222
TI  - Ultrasound bone measurements in pre-adolescent girls: interaction between
      ethnicity and lifestyle factors.
AB  - AIM: We obtained calcaneal ultrasound measurements in 198 girls between 7.5 and
      11.7 y of age, representing ethnic groups (black [n = 80], white [n = 41], mixed
      ancestral origin [n = 77]) in South Africa. METHODS: Anthropometry was assessed.
      Demographics, physical activity, habitual dietary calcium intake and pubertal
      development were quantified by questionnaires. Broadband ultrasound attenuation
      (BUA) and speed of sound (SOS) of the left calcaneus were measured. Girls in
      Tanner breast stage 5 and/or those menstruating were excluded from analysis.
      RESULTS: Black girls were lighter than white girls (31.4 +/- 7.8 vs 34.8 +/- 7.5
      kg; p < 0.05), and shorter than girls of mixed ancestral origin (1.29 +/- 0.08 vs
      1.34 +/- 0.07 m; p < 0.001) and white girls (1.35 +/- 0.07 m; p < 0.001), after
      adjusting for age. Reported calcium intake scores were higher in black than white
      girls (21.6 +/- 11.1 vs 16.1 +/- 8.4; p < 0.01). Total peak bone strain score
      (TPBSS) was higher in white compared to black girls (6.8 +/- 4.8 vs 5.0 +/- 4.7;
      p < 0.05), while walking energy expenditure (MET h/wk) was higher in black girls
      compared to the other groups (p < 0.001). BUA and SOS were higher in the black
      girls (59.6 +/- 13.7 dB/MHz; 1575.1 +/- 22.6 m/s; p < 0.001) and girls of mixed
      ancestral origin (59.0 +/- 12.5 dB/MHz; 1567.8 +/- 26.1 m/s; p < 0.01) than in
      the white girls (50.4 +/- 8.7 dB/MHz; 1552.1 +/- 19.5 m/s). Co-varying for age
      and weight did not affect these results. Walking energy expenditure (r = 0.20)
      and calcium score (r = 0.17) were correlated (p < 0.05) with SOS for the whole
      group. CONCLUSION: Ultrasound parameters were lower in the white compared to the
      black girls, who consumed more calcium on average, but who were lighter, shorter
      and performed less impact activity. This suggests that interactions between
      ethnicity and lifestyle factors determine bone quality in premenarcheal girls.

PMID- 15244223
TI  - Monitoring of IgE-mediated food allergy in childhood.
AB  - BACKGROUND: The prevalence of IgE-mediated food allergy (FA) in childhood varies
      from 6% to 8% in the first year of life compared to 1% to 2% in adults. In
      contrast to adults, FA in childhood, often part of the "allergic march", resolves
      in more than 85% of children, especially those with hypersensitivity to cow's
      milk and egg. AIM: This paper explains the rationale for continuing care for
      childhood FA and describes how children should be monitored for
      resolution/persistence of FA. METHODS: A clinical, multidisciplinary approach and
      management algorithm based on relevant, peer-reviewed original research articles
      and reviews using the keywords anaphylaxis, atopic eczema, children, milk
      allergy, double-blind placebo-controlled food challenge, egg allergy,
      epinephrine, failure to thrive, food allergy, food challenge, food
      hypersensitivity, immunoglobulin E, nutrition, natural history, paediatrics,
      peanut allergy, prevalence, psychosocial factors, quality of life,
      radioallergosorbent test, and tolerance from years 1966 to 2003 in MEDLINE.
      Additional studies were identified from article reference lists. RESULTS: A
      combination of outcome measures, a multidisciplinary approach involving a
      dietitian and allergy nurse specialist, and a management algorithm are useful
      tools in clinical management. CONCLUSIONS: Prospective studies of non-selected
      children, optimally from birth cohorts, are needed to evaluate the effects of
      such management programmes regarding FA in childhood.

PMID- 15244224
TI  - A high neonatal serum eosinophil cationic protein level is a risk factor for
      atopic symptoms.
AB  - AIM: To show whether neonatal eosinophil counts (EC) and eosinophil cationic
      protein (ECP) can be used in assessing the risk of atopy, alone or in combination
      with family history of atopy (FHa). PATIENTS AND METHODS: A group of 63 newborns
      was included: 38 with FHa, 25 without FHa. A blood sample was collected on the
      4th day of life for EC and ECP evaluation. Clinical follow-up was conducted after
      1, 3, 6, 12, 18, 24 and 36 mo. The chi2 test and the Student's t-test were used
      to compare dichotomic and continuous variables, respectively. Variables shown to
      be significant by univariate analysis were evaluated with a multivariate
      regression model and the relative risks (RR) were estimated. RESULTS: Twenty-six
      newborns (41%) displayed atopic manifestations during the follow-up. Twenty-one
      (55%) of 38 newborns with FHa displayed atopic symptoms versus 5/25 (20%) without
      FHa (p 0.012). Neither EC nor serum ECP levels were significantly different
      between newborns with FHa and newborns without. ECP levels did not differ between
      newborns with single heredity and newborns with dual heredity. EC did not differ
      significantly between newborns who developed atopy and those who did not.
      Instead, serum ECP levels were significantly higher in newborns who developed
      atopy (mean 27.9 microU/l vs 16.8 microU/l). Atopic manifestations appeared in 16
      (62%) of 26 newborns with ECP > or = 18 microU/l compared with 10 (27%) of 37
      with ECP < 18 microU/l (p = 0.006). In the multivariate regression model, with
      ECP < 18 microU/l and no FHa as reference class, the class 1 (no FHa and ECP > or
      = 18 microU/l) has a low RR (1.4), class 2 (FHa and ECP < 18 microU/l) an
      intermediate RR (2.7) and class 3 (FHa and ECP > or = 18 microU/l) a very high RR
      (16.3). CONCLUSIONS: Neonatal serum ECP levels, in contrast with EC, were
      significantly higher in newborns who developed atopic manifestations during
      follow-up. The risk of atopy was about twice as great when ECP was > or = 18
      microU/l (and four times as great in multivariate analysis). When serum ECP was
      combined with FHa, the RR for newborns with FHa and ECP > or = 18 microU/l was 16
      times greater than for those without FHa and ECP < 18 microU/l. The
      identification of newborns at "extremely high atopic risk" (FHa and ECP > or = 18
      microU/l) may be expecially useful--in clinical practice--in newborns with only
      one atopic parent or sibling, for whom it is not universally agreed that dietary
      and environmental prevention measures should be applied.

PMID- 15244225
TI  - Increased QT dispersion in breath-holding spells.
AB  - AIM: Breath-holding spells are common in infancy and early childhood, and
      patients are frequently referred to paediatric cardiology clinics for exclusion
      of heart disease. Recent data reveal subsequent development of epilepsy and
      neurocardiogenic syncope. Autonomic dysregulation and increased vagal stimulation
      leading to cardiac arrest and cerebral ischaemia is considered as the cause. Iron
      deficiency anaemia may be associated with these spells. We studied QT dispersion
      for the assessment of ventricular repolarization in these patients. METHODS: The
      study group consisted of 19 girls and 24 boys between 3 and 108 mo of age (mean
      +/- SD = 22.7 +/- 17.7 mo); and the control group consisted of 13 girls and 12
      boys between 3 and 57 mo of age (mean +/- SD = 22.9 +/- 15.1 mo). QT interval was
      measured; corrected QT interval (QTc), QT dispersion (QTd) and QTc dispersion
      (QTcd) were calculated from 12-lead surface electrocardiograms of the patients
      and the control group. RESULTS: There was no statistically significant difference
      in terms of QT and QTc intervals between patient and control groups, while QTd
      and QTcd values were significantly increased in patients with breath-holding
      spells compared to the healthy children. QT dispersion was 59.5 +/- 35.9 ms and
      44.8 +/- 11.9 ms, respectively, in patients and controls (p < 0.05). QTc
      dispersion was 102.1 +/- 41.9 ms and 79.6 +/- 24.6 ms, respectively (p < 0.01).
      The presence of iron deficiency did not effect the QT and QTc dispersion.
      CONCLUSION: QT dispersion is increased in patients with breath-holding spells,
      and this finding justifies further investigation for rhythm abnormalities and
      autonomic dysfunction in this patient group.

PMID- 15244226
TI  - The effect of prenatal consultation with a neonatologist on human milk feeding in
      preterm infants.
AB  - OBJECTIVE: To study the effect of prenatal consultation (PC) with a neonatologist
      on the incidence and duration of human milk feeding (HMF) in preterm infants.
      DESIGN/METHODS: A retrospective matched case-control study was preformed at a
      perinatal centre. Study infants were preterm infants (23-35 wk) whose mothers had
      received PC emphasizing the importance of HMF. Control infants were matched by
      birthweight, gestational age and multiplicity. RESULTS: Each group included 29
      mothers and 46 preterm infants. Mean gestational age was 30.1 +/- 3 wk in both
      groups. Mean birthweight was 1329 +/- 489 (PC) and 1334 +/- 441 g (control). PC
      infants received HMF for significantly longer, both in the hospital and after
      discharge (hospital: PC 37 +/- 34 d vs control 15 +/- 19 d, p = 0.001; discharge
      PC 60 +/- 57 d vs control 21 +/- 32 d; p = 0.0001). No significant difference in
      neonatal morbidity was detected between the groups. CONCLUSIONS: PC is associated
      with significantly longer HMF in preterm infants, both in hospital and after
      discharge.

PMID- 15244227
TI  - Randomized controlled trial of skin-to-skin contact from birth versus
      conventional incubator for physiological stabilization in 1200- to 2199-gram
      newborns.
AB  - AIM: Conventional care of prematurely born infants involves extended maternal
      infant separation and incubator care. Recent research has shown that separation
      causes adverse effects. Maternal-infant skin-to-skin contact (SSC) provides an
      alternative habitat to the incubator, with proven benefits for stable prematures;
      this has not been established for unstable or newborn low-birthweight infants.
      SSC from birth was therefore compared to incubator care for infants between 1200
      and 2199 g at birth. METHODS: This was a prospective, unblinded, randomized
      controlled clinical trial; potential subjects were identified before delivery and
      randomized by computerized minimization technique at 5 min if eligible.
      Standardized care and observations were maintained for 6 h. Stability was
      measured in terms of a set of pre-determined physiological parameters, and a
      composite cardio-respiratory stabilization score (SCRIP). RESULTS: 34 infants
      were analysed in comparable groups: 3/18 SSC compared to 12/13 incubator babies
      exceeded the pre-determined parameters (p < 0.001). Stabilization scores were
      77.11 for SSC versus 74.23 for incubator (maximum 78), mean difference 2.88 (95%
      CI: 0.3-5.46, p = 0.031). All 18 SSC subjects were stable in the sixth hour,
      compared to 6/13 incubator infants. Eight out of 13 incubator subjects
      experienced hypothermia. CONCLUSION: Newborn care provided by skin-to-skin
      contact on the mother's chest results in better physiological outcomes and
      stability than the same care provided in closed servo-controlled incubators. The
      cardio-respiratory instability seen in separated infants in the first 6 h is
      consistent with mammalian "protest-despair" biology, and with "hyper-arousal and
      dissociation" response patterns described in human infants: newborns should not
      be separated from their mothers.

PMID- 15244228
TI  - Methicillin-resistant Staphylococcus aureus bacteraemia in neonatal intensive
      care units: an analysis of 90 episodes.
AB  - AIM: To delineate the clinical features of methicillin-resistant Staphylococcus
      aureus (MRSA) bacteraemia in infants hospitalized at the neonatal intensive care
      unit. METHODS: Episodes of MRSA bacteraemia in Chang Gung Children's Hospital
      neonatal intensive care unit from 1997 to 1999 were reviewed for incidence,
      predisposing factors, clinical presentations, treatment and outcome. RESULTS:
      Ninety episodes of MRSA bacteraemia were identified. The overall rate of MRSA
      bacteraemia was 1.05 per 1000 patient days during the 3-y period. Most of the
      patients were premature infants (76%), with prior operation or invasive
      procedures (39%), had an indwelling intravascular catheter (79%) and exposure to
      antibiotic therapy (96%). A localized cutaneous infection was found in 53.3% of
      the episodes. The most common clinical diagnoses were catheter-related infections
      (54.4%), skin and soft tissue infections (21.1%), bacteraemia without a focus
      (20%) and pneumonia (16.7%). Metastatic infection occurred in 18% of these
      infants. Among the patients treated with vancomycin for < or = 14 d, 88.7% did
      not develop any complications, and 11.3% developed a recurrence. CONCLUSIONS:
      MRSA is an established pathogen in our NICU. MRSA bacteraemia in the neonates
      predominantly presented as catheter-related infections, and metastatic infections
      were not infrequently seen. In uncomplicated MRSA bacteraemia, treatment with
      vancomycin for < or = 14 d seems to be adequate.

PMID- 15244229
TI  - The role of matrix metalloproteinases -9 and -2 in development of neonatal
      chronic lung disease.
AB  - AIM: Matrix metalloproteinases (MMPs) -9 and -2 degrade type-IV collagen, a major
      constituent of lung basement membrane, and may have a role in the pathogenesis of
      neonatal chronic lung disease (CLD). We determined factors influencing MMP levels
      in neonatal bronchoalveolar lavage (BAL) fluid to establish whether an imbalance
      between MMP and its inhibitor could be implicated in CLD. METHODS: We measured
      MMP-9 and -2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in 316
      BAL fluid samples from 121 babies of gestational ages 23 to 42 wk over the first
      14 d of life to determine effects of gestation and postnatal age. Median MMP-9, 
      2, TIMP-1 and MMP-9/TIMP-1 ratio in BAL were further studied in a subgroup of 85
      babies <33 wk gestation to determine their ability to predict CLD and to
      establish effects of antenatal corticosteroid therapy (ANCS). RESULTS: MMP-9, -2
      and TIMP levels did not vary with postnatal age over the first week. Median MMP-9
      levels and MMP-9/TIMP-1 ratio increased with decreasing gestation in preterm
      babies. The MMP-9/TIMP-1 ratio was higher in babies who developed CLD, implying a
      proteinase/antiproteinase imbalance, but this association disappeared when
      controlled for gestational age. ANCS had no effect on BAL fluid MMP or TIMP
      levels. CONCLUSION: MMPs may have a role in the development of lung injury and
      fibrosis, but estimating their levels in the first week of life does not help
      with prediction of CLD.

PMID- 15244230
TI  - Prediction of early tolerance to enteral feeding by measurement of superior
      mesenteric artery blood flow velocity: appropriate- versus small-for-gestational
      age preterm infants.
AB  - AIM: To evaluate whether serial Doppler measurements of superior mesenteric
      artery blood flow velocity could predict early tolerance to enteral feeding in
      preterm infants. METHODS: In a prospective study, 54 healthy preterm neonates
      were assigned to one of the following groups: neonates with birthweight
      appropriate for gestational age (group 1), neonates small for gestational age
      without (group 2) and with prenatal haemodynamic disturbances (group 3). We
      studied Doppler blood flow velocity and resistance index before and after the
      first feed. RESULTS: Contrary to patients of group 3, infants in groups 1 and 2
      showed a significant increase in blood flow velocity and a significant decrease
      in resistance index from the preprandial values after the first feed. At each
      postprandial time, we found significant differences in all velocity and
      resistance measurements between patients of group 3 and patients of both groups 1
      and 2. In all patients, we found that the value of mean velocity measured 30 min
      after the first feed was the most predictive of early feed tolerance, with 95%
      sensitivity and 94% specificity when mean velocity >0.38 m/s. CONCLUSION: Small
      for-gestational-age preterm infants with prenatal haemodynamic disturbances have
      an unusual intestinal haemodynamic response to the first feed. In the whole group
      of preterm infants, the value of mean velocity measured 30 min after the first
      feed is a good tool for the clinician in predicting early enteral feeding.

PMID- 15244231
TI  - Relationship of maternal autoimmune response to clinical manifestations in
      children with congenital complete heart block.
AB  - OBJECTIVE: To study the autoimmune response in mothers of children with
      congenital heart block (CHB) diagnosed at different ages and with different
      clinical manifestations. PATIENTS AND METHODS: Clinical data and sera for the
      determination of immunological tests were available from 104 mothers of 113
      children born between 1950 and 2000 and diagnosed with CHB before the age of 16
      y. Prenatal diagnosis was performed in 74 (65%) children of 65 mothers, and 39
      (35%) children had postnatal diagnosis of CHB. Maternal antibodies to 52 kd and
      60 kd SS-A, and to 48 kd SS-B were determined by time-resolved fluoroimmunoassay
      (TR-FIA) and to antinuclear antibodies (ANA) by immunoflurescense (IF). RESULTS:
      Out of the 65 mothers of children with in utero diagnosed CHB, 88% had antibodies
      to 52 kd SS-A and 83% had ANA. Antibodies to 60 kd SS-A and 48 kd SS-B were less
      frequently present, in 48% and in 54% of the mothers, respectively. Seven (11%)
      of the mothers were negative by all immunoassays. Of the 13 mothers of children
      with in-infancy diagnosed CHB, one mother had high-titer ANA. After 1 y of age,
      CHB was diagnosed in 26 children; at 1 to 6 y in 16 and after 7 y in 10 children;
      1/16 and 1/10 patients had positive antibodies. In all twin pregnancies (n = 4)
      and in all families with recurring cases of CHB (n = 5), maternal antibodies were
      positive in at least one assay. The titer of 48 kd anti-SS-B antibodies was
      significantly higher in children with cutaneous neonatal lupus (98.1 vs 41.0; p =
      0.02). All mothers whose children died before the age of 4 y (n = 8) and 85%
      (11/13) of mothers whose children developed cardiomyopathy had elevated antibody
      titers in at least one assay. However, we could not find any prognostic value of
      maternal antibody levels or specificities on the clinical outcome of the children
      with CHB. CONCLUSIONS: Although rare, late detection or postnatal progression of
      CHB in antibody-mediated CHB should be taken into consideration. Maternal
      antibody levels or specificities have prognostic effect neither on the clinical
      outcome of the child with CHB nor on the risk of reappearance in the same family.

PMID- 15244232
TI  - Nicotine exposure in breastfed infants.
AB  - AIM: To study exposure to nicotine in breastfed infants in relation to parental
      smoking habits. MATERIAL AND METHODS: Forty mother-infant pairs were studied.
      Twenty non-smoking mothers, 18 smoking (2-20 cigarettes per day) and two snuff
      taking mothers were included. All infants were healthy, exclusively breastfed and
      their postnatal age was 6 wk. During a home visit, parental smoking habits were
      recorded, and the time of mothers' last smoke or taking of snuff and
      breastfeeding were recorded. Breast milk and infant urine samples were collected.
      Concentrations of nicotine and cotinine were analysed with gas chromatography.
      The amount of milk ingested during the home visit was calculated by weighing the
      infants. RESULTS: Two non-smoking and non-snuff-taking women had milk containing
      nicotine (28 and 13 microg/l, respectively). Both had smoking spouses. In the
      smoking and snuff-taking group, the mean (SD) milk nicotine concentration was 44
      (38) microg/l (n = 36). When milk samples taken 7 h and 0.6 h after smoking were
      compared, the concentration of milk nicotine increased from 21 to 51 microg/l (p
      < 0.01). The two snuff-taking mothers exposed their children to higher milk
      nicotine concentrations than all but two of the smokers. The concentrations of
      the metabolite cotinine in infant urine correlated with the dose of nicotine
      ingested during the home visit (r = 0.84, p < 0.01). CONCLUSIONS: Breastfed
      infants with a smoking or snuff-taking mother are exposed to nicotine in breast
      milk. The mean intake of nicotine via milk is 7 microg/kg/d. With a shorter time
      between the mothers' smoking and breastfeeding, the milk nicotine concentration
      will increase. Both passive smoking at home and snuff-taking were associated with
      measurable nicotine levels in milk. Healthcare personnel promoting breastfeeding
      should be aware of these factors influencing exposure to nicotine in the
      breastfed infant.

PMID- 15244233
TI  - Height, weight, body mass index and pubertal development references for children
      of Moroccan origin in The Netherlands.
AB  - AIM: To provide growth and sexual maturation reference data for Moroccan children
      living in The Netherlands and to compare them with the reference data of children
      of Dutch origin. METHODS: Cross-sectional growth and demographic data were
      collected from 2880 children of Moroccan origin and 14,500 children of Dutch
      origin living in The Netherlands in the age range 0-20 y. Growth references for
      length, height, weight, weight-for-height, body mass index (BMI) and head
      circumference were constructed with the LMS method. Predictive variables for
      height and BMI were assessed by regression analyses. Reference curves for sexual
      maturation were estimated by a generalized additive model. RESULTS: Moroccan
      young adults were on average 9 cm shorter than their Dutch contemporaries. Mean
      final height was 174.7 cm for males and 161.3 cm for females. Height differences
      in comparison with Dutch children increase from 2 y onwards. Height SDS was
      predominantly associated with target height. Compared to Dutch children,
      maturation started 0.2 and 0.9 y later for girls and boys, respectively. Median
      age at menarche was 12.9 y, 3.6 mo earlier than in Dutch girls (p = 0.001). BMI
      of Moroccan children was above that of Dutch children, especially for girls. BMI
      SDS was associated with birthweight in the age group 0 - < or = 5 y. CONCLUSION:
      Moroccan children living in The Netherlands are substantially shorter than Dutch
      children. Girls have higher weight-for-height and BMI for age. Median age at
      menarche occurs earlier. Given these differences, separate growth charts for the
      Moroccan children are useful.

PMID- 15244234
TI  - Intestinal microflora in breastfed colicky and non-colicky infants.
AB  - BACKGROUND: Infantile colics are a common problem in the first months of life.
      During this period, a process of intestinal colonization rapidly occurs. A
      difference in the gut microflora could play an important role in the pathogenesis
      of colics, changing the metabolism of carbohydrates and fatty acids. Actually, in
      the literature, only few data have been collected about this topic. In this
      study, we evaluated intestinal microflora in breastfed colicky and non-colicky
      infants. METHODS: Seventy-one breastfed infants, aged 3.2 +/- 0.6 wk, free from
      episodes of gastroenteritis and without previous assumption of antibiotic and
      probiotic drugs, were enrolled in the study. They were divided into two groups:
      colicky (42 cases) and non-colicky (29 cases), according to Wessel's criteria.
      Stool samples were collected, diluted and cultured on several selective media to
      detect lactobacilli, clostridia, gram-negative anaerobes and Enterobacteriaceae.
      Statistical analysis was performed using Student's t-test, chi2 test and a non
      parametric test (Mann-Whitney U-test). RESULTS: Differences in gut microflora
      were found among colicky and non-colicky infants: colicky infants were less
      frequently colonized by Lactobacillus spp., and more frequently by anaerobic gram
      negative bacteria. CONCLUSION: Our study indicates that colicky infants have
      different patterns of gut microflora. Further studies are required to understand
      whether gut microflora is the primary cause of colics or its consequence.

PMID- 15244235
TI  - A comparison of Likert scale and visual analogue scales as response options in
      children's questionnaires.
AB  - AIM: To examine which response options children prefer and which they find
      easiest to use, and to study the relative reliability of the different response
      options. METHODS: A consecutive group of unselected children (n = 120) filled out
      three questionnaires in a paediatric outpatient clinic. Each questionnaire
      included seven similar questions, but had different response options: the Likert
      scale, the Visual Analogue Scale (VAS) and the numeric VAS. In general, the
      questions were not related to the children's particular diseases, but dealt with
      the frequency of simple activities, their feelings and opinions. The pages with
      the three different response options were offered in random order. Afterwards,
      the children rated their preference and ease of use of the different response
      options on a scale from one to 10. RESULTS: Children preferred the Likert scale
      (median mark 9.0) over the numeric VAS (median mark 8.0) and the simple VAS
      (median 6.0). They considered the Likert scale easiest to fill out (median mark
      10 vs 9 and 7.5 for the numeric and simple VAS, respectively). Results of the
      different response options correlated strongly with each other (rho = 0.67-0.90,
      p < 0.05). CONCLUSION: Children prefer the Likert scale over the numeric and
      simple VAS and find it easiest to complete. The Likert scale, the simple VAS and
      the numeric VAS are of comparable reliability. The Likert scale is recommended
      for use in questionnaires for children, although research into larger and more
      diverse samples is needed.

PMID- 15244236
TI  - Prevalence and significance of minor anomalies in children with impaired
      development.
AB  - AIM: To compare the prevalence of Waldrop's minor physical anomalies in children
      with developmental disorders (mental retardation, hearing and visual impairment)
      and healthy schoolchildren. METHODS: The study was carried out on a sample of 469
      children (223 children with developmental disorders and 246 healthy
      schoolchildren). RESULTS: Significant differences were found between the children
      with developmental disorders and the healthy children with regard to the number
      of minor anomalies and their weighted scores according to Waldrop. Multivariate
      discriminant analysis with two discriminative functions explained as much as
      96.51% of the total variability and significantly distinguished the healthy
      children from the children with developmental disorders. However, no clear
      distinction was found between the mentally retarded children and those with
      visual impairment. Interrelation of the number and sum of the weighted scores of
      minor anomalies showed similar minor anomalies in the mentally retarded children
      (mean per person 3.65 and 3.82, respectively), the children with visual
      impairment (3.24 and 3.50), the children with hearing impairment (3.84 and 3.67)
      and the control group (1.70 and 1.46), although at different levels. CONCLUSIONS:
      The high prevalence of multiple minor anomalies in children with developmental
      disorders suggests that during early development, factors which cause the
      specific developmental disorder and the occurrence of a minor anomaly have a
      joint effect.

PMID- 15244237
TI  - Successful use of recombinant factor VIIa for management of severe menorrhagia in
      an adolescent with an acquired inhibitor of human thrombin.
AB  - Antibodies directed against human thrombin are exceedingly rare, having only been
      reported in adult patients with underlying diseases. Consensus on the most
      appropriate management has not yet been reached. A 12-y-old girl presented with
      intractable menorrhagia several days after an acute infectious episode.
      Laboratory tests revealed disturbed clotting tests: prothrombin index 17%,
      activated partial thromboplastin time >150 s, thrombin time >120 s, and failure
      to achieve correction with a normal pooled plasma. Further studies demonstrated
      the presence of an antibody directed against human thrombin. Viral serology
      revealed a 1/128 titre for adenovirus. Massive haemorrhage was unresponsive to
      standard treatments, but intravenous administration of recombinant factor VIIa
      resulted in a successful outcome. CONCLUSION: This is the first report of an anti
      human thrombin antibody associated with severe bleeding in a child. Recombinant
      factor VIIa could represent a novel therapeutic approach for such patients.

PMID- 15244238
TI  - Video reveals self-stimulation in infancy.
AB  - The medical literature on early childhood masturbation is sparse. Only 12
      patients who presented with infantile self-stimulation under the age of 1 y are
      described. During the last 2 y, five girls under 1 y of age presented at our
      department with self-stimulating behaviour. The diagnosis of this behaviour was
      difficult, but could be made by watching a video of the attacks. Infantile self
      stimulation is often misdiagnosed and unnecessary investigations and useless
      treatments are often prescribed. Video recording can be of great help to put
      forward the correct diagnosis. Masturbation is not so uncommon and treatment
      consists mostly in reassuring the parents. It can, however, be associated with
      behavioural problems. Few data are available on the clinical outcome of childhood
      masturbation, but most children seem to develop normally. CONCLUSION: Infantile
      self-stimulation should always be considered in the differential diagnosis of
      "strange episodes or attacks".

PMID- 15244239
TI  - Characteristics of respiratory syncytial virus-related apnoea in three infants.
AB  - Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young
      infants and can be the first presentation of an acquired RSV infection. We
      describe polysomnographic recordings of three infants revealing prolonged RSV
      related apnoea before RSV infection was diagnosed. The apnoeas were of central
      origin. The caregivers had not noted any apparent life-threatening events (ALTE)
      prior to the polysomnography. Cardiorespiratory monitoring after the acute
      infection did not reveal any further apnoeas. CONCLUSION: Central, prolonged
      apnoea can be the first sign of an acquired RSV infection in young infants in the
      absence of other respiratory symptoms and without any previous observation of
      apnoea by the caregivers.

PMID- 15244240
TI  - Linear IgA bullous dermatosis of neonatal onset: case report and review of the
      literature.
AB  - Several small blisters were noticed on the forehead and the trunk of a newborn
      boy on day 1. The blisters gradually enlarged and spread over the whole body
      including the oral mucosa. A skin biopsy was performed twice and subepidermal
      bullae with polymorphonuclear and mononuclear cell infiltration were
      demonstrated. Direct immunofluorescence showed linear IgA, IgG and C3 depositions
      along the basement membrane zone and this finding led to a diagnosis of linear
      IgA bullous dermatosis. So far, internationally, only one case has ever been
      reported on the disease at neonatal onset. The skin lesions spontaneously
      regressed and the mucosal lesions were controlled with diaminodiphenylsulfone.
      CONCLUSION: In neonates with prolonged blistering, autoimmune disease such as
      linear IgA bullous dermatosis should be considered within the differential
      diagnosis and an immunofluorescence study must be performed.

PMID- 15244241
TI  - New findings in partial trisomy 16q: clinical report.
AB  - Partial trisomy 16q is a rare disorder associated with significant dysmorphism,
      psychomotor retardation and limited postnatal survival. A female infant with a
      partial trisomy 16q from a de novo translocation 11;16 is described. Clinical
      findings were consistent with previous reports, with the exceptions of
      megalocornea, partial callosal agenesis and mild bilateral occipital lobe
      hypoplasia. CONCLUSION: Based on this clinical report, megalocornea, partial
      callosal agenesis and mild bilateral occipital lobe hypoplasia should perhaps be
      included in the list of anomalies associated with partial trisomy 16q.

PMID- 15244242
TI  - Fatty acid composition of human milk lipids in Chilean women.

PMID- 15244243
TI  - Severe acute respiratory syndrome in children: a clue to better understanding the
      disease and advancing towards solutions.

PMID- 15244244
TI  - How reliable is clinical assessment in neonatal jaundice?

PMID- 15244245
TI  - Proxy ratings of patient quality of life--factors related to patient-proxy
      agreement.
AB  - It is generally agreed that patients are the best raters of their quality of life
      (QL). Where it is not possible to obtain information from the patient the use of
      proxies can be an alternative. The proxy can be a significant other or a
      healthcare provider. The use of a proxy offers a solution to non-response. The
      accuracy of proxy reports is most typically determined by examining the extent to
      which patient and proxy ratings agree. A literature overview shows that agreement
      depends on several factors. Methodological limitations may have an impact on
      agreement. Agreement also varies according to the QL domains under study; the
      highest agreement is usually found for concrete domains. In addition, patient and
      proxy characteristics are related to agreement. When designing QL studies the
      threat of selection bias due to exclusion of patients has to be balanced against
      the threat of information bias due to proxy ratings.

PMID- 15244246
TI  - Mutation and accumulation of p53 related to results of adjuvant therapy of
      postmenopausal breast cancer patients.
AB  - p53 protein accumulation and gene mutation have been implicated in resistance to
      cytotoxic treatment. This study was performed to further assess the predictive
      value of p53 in breast cancer. Postmenopausal patients were randomized to
      adjuvant chemotherapy with cyclophosphamide, metothrexate, or 5-fluorouracil
      (CMF) vs. postoperative radiotherapy. The patients were also randomized to
      adjuvant tamoxifen vs. no endocrine treatment. Immunohistochemistry (IHC) and
      single-strand conformation polymorphism (SSCP), followed by direct sequencing,
      was performed. The p53 altered group, regarded as positive for p53 gene mutation
      and/or p53 protein accumulation, tended to benefit more from CMF than from
      radiotherapy as compared with others regarding distant recurrences. In the group
      lacking p53 alteration there was a significantly decreased local recurrence rate
      in the radiotherapy group as compared with the CMF group (RR = 0.24, 95% CI =
      0.083 0.62), whereas no benefit from radiotherapy was found for patients showing
      p53 alterations. Tamoxifen significantly decreased the rate of distant recurrence
      for estrogen receptor-positive patients with no apparent difference in relation
      to p53 alteration. It is suggested that p53 alteration indicates benefit from CMF
      compared with radiotherapy regarding distant recurrence-free survival and the
      best local control with radiotherapy is achieved in the absence of p53
      alteration. Finally, altered p53 status is probably not a marker of resistance to
      tamoxifen.

PMID- 15244247
TI  - A phase I safety and pharmacokinetic study of OGT 719 in patients with liver
      cancer.
AB  - OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with
      a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the
      capacity selectively to bind to asialoglycoprotein receptors that are found
      exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of
      this study was to establish the safety and to examine the pharmacokinetics of
      this novel compound in patients with liver cancer. Fourteen patients received a
      total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000
      mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was
      administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for
      5 days every 4 weeks. Pharmacokinetic parameters were studied during the first
      cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The
      maximum plasma concentration was attained within 5 min of completing the infusion
      and almost doubled, dose dependently, with a doubling of the infused dose. The
      plasma level declined rapidly in a monophasic manner with an elimination half
      life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under
      the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity),
      area under the curve to infinity) doubled at the higher dose level. None of the
      patients had a significant tumor response. Elimination half-life of OGT 719 by 3
      h intravenous infusion is short and monophasic. Toxicity was minimal at the
      highest dose level.

PMID- 15244248
TI  - Reactive oxygen species production by blood neutrophils of patients with
      laryngeal carcinoma and antioxidative enzyme activity in their blood.
AB  - Squamous cell carcinoma of the head and neck is a devastating illness with a
      severe impact on affected individuals. Several mechanisms may lead to oxidative
      stress in tumor-bearing patients, among others chronic inflammation. Inflammatory
      cells, especially macrophages and neutrophil leukocytes, may produce reactive
      oxygen species (ROS) which participate in carcinogenesis and tumor-associated
      immunosuppression. The aim of the study presented in this paper was to compare
      the production of reactive oxygen species (ROS)--superoxide anion (O2-) and
      hydrogen peroxide (H2O2)--by neutrophils isolated from the blood of 16 patients
      with larynx carcinoma and 15 healthy controls. The serum activity of superoxide
      dismutase and catalase as well as the total peroxidase activity in serum have
      also been estimated. The production of ROS, especially spontaneous and phorbol 12
      myristate 13-acetate (PMA)-induced O2-, was relatively higher in the patients
      with larynx carcinoma than in the healthy controls and increased parallel with
      the tumor stage (tumor, node, metastasis-TNM staging). The serum activity of
      catalase and peroxidase was also highest in the patients with stage T3 and T4
      larynx carcinoma. After partial or total laryngectomy, a significant decrease in
      ROS production and the serum activity of catalase and peroxidase was observed. In
      contrast, the serum level of superoxide dismutase, which had been low prior to
      surgery, especially in the patients with advanced tumor stages (T3-T4), increased
      significantly afterwards. The results indicate the existence of oxidative stress
      in the blood of patients with larynx carcinoma and its significant decrease after
      partial or total laryngectomy.

PMID- 15244249
TI  - Biopolymer-mediated suramin chemotherapy in the treatment of experimental brain
      tumours.
AB  - Suramin inhibits tumour growth and neoangiogenesis by blocking several growth
      factor receptors. In this study the toxicity and efficacy of intralesional
      delivery of suramin incorporated in a controlled-release polymer were assessed in
      a rat 9L tumour model. Initially, the toxicity of the compound was evaluated in
      adult Fisher 344 rats. The animals were intracerebrally implanted with an
      ethylene vinyl acetate copolymer. These experiments showed early toxicity in the
      rats implanted with a 50% load-polymer and 100% mortality within 48 h, whereas in
      rats implanted with a 33% load-polymer only transient behavioural changes were
      observed. In a second experiment the rats were stereotactically implanted with 9L
      cells in the frontal region. Two days after inoculation of cells, the animals
      were divided into two groups: one group received a 33% suramin load-biopolymer at
      the tumour implantation site, while the control group received polymer implants
      only. The interstitial release of suramin in the brain did not produce any
      improvement in survival of 9L tumour-bearing rats, with a mean survival of 14.2
      +/- 1 days for the suramin-treated group versus 13.8 +/- 2 for the control group
      (p = 0.82). We conclude that intralesional polymer-mediated chemotherapy with
      suramin does not prolong survival in rats with intracerebral 9L tumours.

PMID- 15244250
TI  - A limiting factor for the progress of radionuclide-based cancer diagnostics and
      therapy--availability of suitable radionuclides.
AB  - Advances in diagnostics and targeted radionuclide therapy of haematological and
      neuroendocrine tumours have raised hope for improved radionuclide therapy of
      other forms of disseminated tumours. New molecular target structures are
      characterized and this stimulates the efforts to develop new radiolabelled
      targeting agents. There is also improved understanding of factors of importance
      for choice of appropriate radionuclides. The choice is determined by physical,
      chemical, biological, and economic factors, such as a character of emitted
      radiation, physical half-life, labelling chemistry, chemical stability of the
      label, intracellular retention time, and fate of radiocatabolites and
      availability of the radionuclide. There is actually limited availability of
      suitable radionuclides and this is a limiting factor for further progress in the
      field and this is the focus in this article. The probably most promising
      therapeutic radionuclide, 211At, requires regional production and distribution
      centres with dedicated cyclotrons. Such centres are, with a few exceptions in the
      world, lacking today. They can be designed to also produce beta- and
      Augeremitters of therapeutic interest. Furthermore, emerging satellite PET
      scanners will in the near future demand long-lived positron emitters for
      diagnostics with macromolecular radiopharmaceuticals, and these can also be
      produced at such centres. To secure continued development and to meet the
      foreseen requirements for radionuclide availability from the medical community it
      is necessary to establish specialized cyclotron centres for radionuclide
      production.

PMID- 15244251
TI  - A phase II study of UFT and Leucovorin in combination with mitomycin C in
      patients with metastatic colorectal cancer.
AB  - The main objectives of this phase II study were to determine efficacy and safety
      of the combination of UFT with Leucovorin and mitomycin C in patients with
      metastatic colorectal cancer. Ninety-seven patients were treated with UFT (91
      patients 300 mg/m2, 6 patients 250 mg/m2) + Leucovorin 90 mg days 1-28 q 5 weeks.
      During the first 4 cycles the patients also received mitomycin C 7 mg/m2 on day
      1. At the end of 4 courses patients with benefit from the treatment could receive
      further courses of UFT and Leucovorin alone. Two patients had a complete response
      (2%), 20 (21%) had a partial response, 40 (41%) had no change, 19 (20%) had
      progression, and 16 (17%) were not evaluable for response. The overall response
      rate by intention to treat was 22/97 (23%). Median time to progression was 5
      months and median survival 13 months. Severe (grade 3-4) toxicities included:
      anorexia 3%, nausea 6%, vomiting 7%, diarrhoea 7%, and fatigue 9%. Febrile
      neutropenia, renal failure, and thrombocytopenia were seen in 1% of the patients,
      respectively. The combination of UFT with Leucovorin and mitomycin C shows
      similar clinical activity with regard to overall response rate (23%) and survival
      (13 months) to other frontline 5-fluorouracil-based therapies in metastatic
      colorectal cancer patients. The results indicate that mitomycin C did not
      increase either efficacy or toxicity. Therefore, phase III trials with this
      regimen cannot be recommended.

PMID- 15244252
TI  - Evaluation of arm and shoulder mobility and strength after modified radical
      mastectomy and radiotherapy.
AB  - Seventy-five women, of whom 30 had received postoperative radiotherapy, were
      tested for range of motion (ROM) and shoulder strength with a goniometer and an
      isokinetic device (Orthotron II), respectively. On the individual level,
      irradiated patients exhibited significantly reduced range of motion (varying from
      p < 0.05 to p < 0.001) for all movements compared with the non-operated side. In
      contrast, in the non-irradiated patients only flexion was significantly reduced
      (p < 0.05). The same individual pattern was evident for shoulder strength where
      all movements except external rotation were significantly reduced in irradiated
      patients (varying from p < 0.05 to p < 0.001). Non-irradiated patients exhibited
      a significant reduction in shoulder strength for flexion and abduction (p <
      0.05), whereas other movements were less affected. The observed differences in
      ROM and strength were less pronounced when analyzed on a group level, but were
      still significant for ROM (p < 0.001) for flexion and abduction. Group level
      analysis also showed reduced shoulder strength for all movements but only
      rotation was significantly (p < 0.01) impaired.

PMID- 15244253
TI  - Voice quality after treatment for T1a glottic carcinoma--radiotherapy versus
      laser cordectomy.
AB  - The purpose of this study was to assess the anatomic and functional outcomes and
      compare the voice quality in patients affected by T1a glottic carcinoma treated
      with curative intent with radiotherapy or laser cordectomy. Fifty-seven cases
      were analysed: 27 after curative radiotherapy and 30 after laser cordectomy. All
      patients were studied with videolaryngostroboscopy, voice analysis by narrow
      spectrogram, and vocal parameters (Jitter, Shimmer, noise/harmonic ratio, and
      diplophonia). Videolaryngostroboscopy showed severe glottic inadequacy in 25% of
      cases treated with radiation and insufficient compensation 'ventricular band' or
      'with arytenoid hyperadduction' in 65% of cases after surgery. Severe dysphonia
      on the electro-acoustic analysis of voice was observed in 25% of cases after
      radiation and 70% after laser (p < 0.001). Fundamental frequency and vocal
      parameters showed more favourable results in the radiation group (p < 0.001).
      Voice assessment showed better results after radiotherapy compared with laser
      cordectomy. Voice outcome should be carefully considered in the treatment
      decision for T1 glottic carcinoma.

PMID- 15244254
TI  - The estimated economic value of the welfare loss due to prostate cancer pain in a
      defined population.
AB  - The aim of the study reported here was to estimate the economic value of the
      welfare loss due to prostate cancer pain by estimating the extent to which pain
      affects health-related quality of life among patients with prostate cancer. The
      material consisted of a point estimate of health status among men with prostate
      cancer in a well-defined population of 200000 males. Clinical data concerning the
      disease at diagnosis (extracted from patients' records and the Regional Prostate
      Cancer Registry), and health utility ratings (using EuroQol) were obtained from 1
      156 males with prostate cancer. A descriptive model showed that optimal treatment
      that would reduce pain to zero during the whole episode of disease would add on
      average 0.85 quality-adjusted life years (QALY) to every man with prostate
      cancer. Based on an estimate of the willingness to pay for a QALY the economic
      value of this welfare loss due to prostate cancer pain is in the magnitude of
      Euro 86 600 000 per year (Euro 19 800000 per million men in Sweden).

PMID- 15244255
TI  - Parental longevity and prognosis in elderly patients with aggressive non
      Hodgkin's lymphoma.
AB  - In general, elderly patients with aggressive non-Hodgkin's lymphoma (NHL) have a
      less favourable prognosis than younger patients. Established predictors of
      prognosis in NHL are less discriminatory in the elderly, which is why there is a
      need for additional markers giving guidance on treatment decisions and prediction
      of outcome. The expected length of life of an individual in the general
      population is intimately associated with that of his/her parents. The aim of this
      study was to test the hypothesis that parental longevity is associated with
      improved outcome also among elderly patients with aggressive NHL and thus serves
      as an easily accessible non-disease associated prognostic factor. A total of 220
      patients ( > 60 years) with aggressive NHL with a median age of 71 years (range
      60-86) were included. Patients were randomized to receive CHOP or CNOP
      (doxorubicin replaced with mitoxantrone) chemotherapy with or without the
      addition of granulocyte colony-stimulating factor. The median follow-up time was
      56 (19-89) months. Parental data regarding age at death were available through
      parish offices for 425 (97%) parents. Relative risk (RR) of death (disease
      specific and all-cause) associated with parental lifespan was assessed using Cox
      proportional hazards regression analyses, with adjustment for sex, age,
      prognostic index, symptoms, and calendar period of diagnosis. Maternal lifespan
      below (versus above) median was associated with a borderline significant reduced
      disease-specific (adjusted RR of death from NHL = 1.5; 95% confidence interval
      1.0-2.1) and overall survival. The effect of maternal lifespan was somewhat more
      pronounced in patients receiving CHOP than CNOP treatment. Paternal lifespan
      below the median was associated with a borderline significant increased disease
      specific (adjusted RR of death from NHL = 0.8 [0.5-1.0]) and overall survival.
      Combined, maternal, and paternal lifespan had little impact on survival. These
      effects were true also when CHOP and CNOP treated patients were analysed
      separately. Maternal and paternal lifespan may predict survival in NHL, but with
      opposing effects. At present parental age appears not to be a clinically useful
      predictor of prognosis in the elderly with aggressive NHL.

PMID- 15244256
TI  - Liver insufficiency due to breast cancer metastases--fast biological response
      with capecitabine.

PMID- 15244258
TI  - Biophoton. Preface.

PMID- 15244257
TI  - Guideline for the management of upper respiratory tract infections.
AB  - INTRODUCTION: Inappropriate use of antibiotics for upper respiratory tract
      infections (URTIs), many of which are viral, adds to the burden of antibiotic
      resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae,
      responsible for most cases of acute otitis media (AOM) and acute bacterial
      sinusitis (ABS). METHOD: The Infectious Diseases Society of Southern Africa held
      a multidisciplinary meeting to draw up a national guideline for the management of
      URTIs. Background information reviewed included randomised controlled trials,
      existing URTI guidelines and local antibiotic susceptibility patterns. The
      initial document was drafted at the meeting. Subsequent drafts were circulated to
      members of the working group for modification. The guideline is a consensus
      document based upon the opinions of the working group. OUTPUT: Penicillin remains
      the drug of choice for tonsillopharyngitis. Single-dose parenteral administration
      of benzathine penicillin is effective, but many favour oral administration twice
      daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A
      dose of 90 mg/ kg/day is recommended in general, which should be effective for
      pneumococci with high-level penicillin resistance (this is particularly likely in
      children < or = 2 years of age, in day-care attendees, in cases with prior AOM
      within the past 6 months, and in children who have received antibiotics within
      the last 3 months). Alternative antibiotic choices are given in the guideline
      with recommendations for their specific indications. These antibiotics include
      amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide
      groups of agents and the respiratory fluoroquinolones. CONCLUSION: The guideline
      should assist rational antibiotic prescribing for URTIs. However, it should be
      updated when new information becomes available from randomised controlled trials
      and surveillance studies of local antibiotic susceptibility patterns.

PMID- 15244259
TI  - Properties of biophotons and their theoretical implications.
AB  - The word "biophotons" is used to denote a permanent spontaneous photon emission
      from all living systems. It displays a few up to some hundred photons/(s x cm2)
      within the spectral range from at least 260 to 800 nm. It is closely linked to
      delayed luminescence (DL) of biological tissues which describes the long term and
      ultra weak reemission of photons after exposure to light illumination. During
      relaxation DL turns continuously into the steady state biophoton emission, where
      both, DL and biophoton emission exhibit mode coupling over the entire spectrum
      and a Poissonian photo count distribution. DL is representing excited states of
      the biophoton field. The physical properties indicate that biophotons originate
      from fully coherent and sometimes even squeezed states. The physical analysis
      provides thermodynamic and quantum optical interpretation, in order to understand
      the biological impacts of biophotons. Biological phenomena like intracellular and
      intercellular communication, cell growth and differentiation, interactions among
      biological systems (like "Gestaltbildung" or swarming), and microbial infections
      can be understood in terms of biophotons. "Biophotonics", the corresponding field
      of applications, provide a new powerful tool for assessing the quality of food
      (like freshness and shelf life), microbial infections, environmental influences
      and for substantiating medical diagnosis and therapy.

PMID- 15244260
TI  - Biophoton emission of a lichen species Parmelia tinctorum.
AB  - The properties of biophoton signals emitted by samples of lichen species P.
      tinctorum are investigated. The shape of a light induced signal is determined
      from 5 ms onwards using successively the bin resolution of 1, 10 and 100 ms; 1000
      measurements in successive bins are made at each resolution. The measurement of
      the shape is repeated at various temperatures in the range (1 degree-40 degrees
      C) in steps of 1 degree C. It is found that a biophoton signal is very sensitive
      to temperature and different portions of the signal show different sensitivity.
      The temperature dependence of the decaying part is even qualitatively different
      from that of the non-decaying part. The signal responds to temperature changes of
      0.1 degrees C in less than 1 ms. The effect of monochromatic stimulation on the
      strengths of the signal and its red, blue and green spectral components are
      determined in the wavelength range (400-700) nm in steps of 10 nm. The signal and
      its broad spectral components have similar excitation curves. The relative
      strength of spectral component appears independent of the stimulating wavelength.
      The shape of the decaying portion of the signal and its red, blue and green
      components is also determined. The character of decay in all four cases is non
      exponential. The measurements with various interference filters spanning the
      entire visible region are made with the bin size of 20 s. These measurements are
      qualitative because of large fluctuations but suggest that the spectral
      components of a biophoton signal are distributed in the entire visible region.
      The probabilities of detecting different number of photons in the non-decaying
      portion are determined by making 30,000 measurements in each set with the bin
      size of 50, 100, 200, 300, 400, 500 and 700 ms. The probabilities determine the
      parameters of a squeezed state of light--the magnitude of its displacement
      parameter is different but the phase of its displacement parameter and its
      squeezing parameter are same for different sizes of a bin. These measurements
      further indicate that the average signal strength remains constant for 19 hr.

PMID- 15244261
TI  - Oscillations in ultraweak photon emission of Acetabularia acetabulum (L.).
AB  - Ultraweak photon emission of dark-incubated A. acetabulum cells were measured
      with the use of a sensitive electronphotomultiplier of the Hamamatsu 550 type.
      The photon count series were subjected to Fourier analysis for 2-1020 sec period
      range. The average level of photon emission in samples containing 50 cells was
      approximately. 40% above background. Cell cultures were prepared at least 24 hr
      before the photon emission measurements and kept un-disturbed ("established
      cultures"). This paper reports results of Fourier analysis of a number of samples
      of Acetabularia cells. In a single population cells periodicity of light emission
      was not defined directly from Fourier transformation. A large number of analyses,
      however, if they are combined and compared with background data, reveal a cell
      culture specific frequency pattern. The results suggest the idea that established
      cell-cultures are characterized by higher intensities of long period (minutes)
      oscillations occurs, while a relative decrease was observed in the short period
      (few seconds) range. The long period oscillations were not detected in cell
      cultures that were prepared within 1 hr before the photon emission measurements.
      It is concluded that Fourier analysis of ultraweak photon emission, even with
      relatively low signals, appears to be possible. It may serve as a non-invasive
      tool for monitoring the physiological state of cells, or for studying the control
      of intercellular dynamics.

PMID- 15244262
TI  - Temperature dependence of ultraweak photon emission in fibroblastic
      differentiation after irradiation with artificial sunlight.
AB  - Yield of ultraweak photon emission in a cell culture model for biophotonic
      measurements using fibroblastic differentiation depended on the temperature of
      photonic measurement. The ultraweak photon emission of medium was significantly
      higher at 37 degrees C than at 25 degrees C and after UVB-irradiation this
      difference was even more pronounced. While with cells in the medium no
      temperature dependence could be determined in unirradiated samples, after UVB
      irradiation of cells an increase of biophotonic emission was observed in
      postmitotic fibroblasts. While after several UVB exposures normal cells begin to
      absorb the ultraviolet light, cells from patients with the disease Xeroderma
      Pigmentosum loose this capacity. In view that fibroblasts play an essential role
      in skin aging, skin carcinogenesis and wound healing, the biophotonic model using
      the fibroblastic differentiation system provides to be a new and powerful non
      invasive tool for the development of skin science.

PMID- 15244263
TI  - Biophotonic patterns of optical interactions between fish eggs and embryos.
AB  - The optical (non-substantial) interactions between various biological samples
      have been evident in a number of cases mainly by the effects on their functional
      activity and developmental patterns. However, the mechanisms of these
      interactions have remained obscure. Effect of optical interaction has been
      observed on the intensity and Fourier patterns of biophoton emission of fish
      embryos. We demonstrate that: (1) the short-term optical interactions are
      accompanied by a gradual decrease of a total emission intensity of the
      interacting batches; (2) this effect is spread laterally to that part of a batch
      which does not have any direct optical contacts with its partner; and (3) the
      long-term optical contacts lead to a mutual exchange of spectral characteristics
      of interacting batches in which the total spectral density values are reversed
      (often with an overshoot). The reversal rate depends upon the developmental
      distance between the optical partners and the initial differences of their
      spectral characteristics. The results are discussed in terms of a sub-radiance
      and Le Chatelier principle.

PMID- 15244264
TI  - Solid state approach in biophoton research.
AB  - Main characteristics of the delayed luminescence (DL) emitted in the seconds
      range from biological systems is analyzed. The correlation between change in DL
      and cell's organization, and similarity with some characteristics of DL from
      solid state system suggest to connect DL in biological system to decay of
      collective electron states, formed during energy and charge transport along the
      macromolecular ordered structures which form the cell. Results of a proposed
      soliton model are discussed, together with some phenomenological evidence which
      emphasize the possibility of using DL measurements as an intrinsic probe in
      biophysical investigations.

PMID- 15244265
TI  - Biophoton emission of human body.
AB  - For the first time systematic measurements of the "ultraweak" photon emission of
      the human body (biophotons) have been performed by means of a photon detector
      device set up in darkness. About 200 persons have been investigated. In a
      particular case one person has been examined daily over several months. It turned
      out that this biophoton emission reflects, (i) the left-right symmetry of the
      human body; (ii) biological rhythms such as 14 days, 1 month, 3 months and 9
      months; (iii) disease in terms of broken symmetry between left and right side;
      and (iv) light channels in the body, which regulate energy and information
      transfer between different parts. The results show that besides a deeper
      understanding of health, disease and body field, this method provides a new
      powerful tool of non-invasive medical diagnosis in terms of basic regulatory
      functions of the body.

PMID- 15244266
TI  - Photon counting statistics analysis of biophotons from hands.
AB  - The photon counting statistics of biophotons emitted from hands is studied with a
      view to test its agreement with the Poisson distribution. The moments of observed
      probability up to seventh order have been evaluated. The moments of biophoton
      emission from hands are in good agreement while those of dark counts of
      photomultiplier tube show large deviations from the theoretical values of Poisson
      distribution. The present results are consistent with the conventional delta
      value analysis of the second moment of probability.

PMID- 15244267
TI  - Left-right asymmetry of biophoton emission from hemiparesis patients.
AB  - Left-right biophoton asymmetry from the palm and the dorsum of hands from 7
      Korean hemiparesis patients were studied. There is a strong tendency that the
      left-hemiparesis patients emit more biophotons from the right than the left
      hands, while the right-hemiparesis patient emits more from the left hand.
      Acupuncture treatment reduces dramatically the left-right asymmetry of biophoton
      emission rates. However there is no systematic difference for the patients in the
      emission rates from the palm and the dorsum of hands.

PMID- 15244268
TI  - Registration of spontaneous photon emission from virus-infected cell cultures:
      development of experimental system.
AB  - Detection of spontaneous photon emission from virus-infected cells was attempted
      using cell monolayer cultures prepared from the established cell lines differing
      by origin and sensitivity to viruses. The experimental system was elaborated
      permitting maintenance of the cell monolayer cultures grown upon quartz slides
      placed inside quartz cuvettes within the photomultiplier chamber during prolonged
      time periods (till 24-36 hr) covering the whole virus multiplication cycle. Rich
      nutritive medium was employed, providing undisturbed cell viability and virus
      induced cytopathic effect (CPE) development during such prolonged experiment,
      each ingredient of the medium being checked as potential parasitic emitter or
      extinguisher of the cell-specific emission. As presupposed 'positive control',
      the in vivo cultivated chorio-allantoic membranes (CAM) of 10-days-old chick
      embryonated eggs were used. The virus-infected CAMs showed specific peculiarities
      of the emission dynamics as compared to monotonous dynamics shown by non-infected
      CAMs. Similar dynamic regularities were observed in cell monolayer cultures
      containing much lesser (by order) number of cells per exposed sample. Using the
      elaborated system, some specific changes in the virus-infected cells were found,
      being correlated with two stages of virus replication cycle: the initial stage,
      synchronous penetration of the pre-adsorbed virus inside the cell, and a later
      stage, characterized by intensive CPE manifestations.

PMID- 15244269
TI  - Biophoton research in blood reveals its holistic properties.
AB  - Monitoring of spontaneous and luminophore amplified photon emission (PE) from non
      diluted human blood under resting conditions and artificially induced immune
      reaction revealed that blood is a continuous source of biophotons indicating that
      it persists in electronically excited state. This state is pumped through
      generation of electron excitation produced in reactive oxygen species (ROS)
      reactions. Excited state of blood and of neutrophil suspensions (primary sources
      of ROS in blood) is an oscillatory one suggesting of interaction between
      individual sources of electron excitation. Excited state of blood is extremely
      sensitive to the tiniest fluctuations of external photonic fields but resistant
      to temperature variations as reflected in hysteresis of PE in response to
      temperature variations. These data suggest that blood is a highly cooperative non
      equilibrium and non-linear system, whose components unceasingly interact in time
      and space. At least in part this property is provided by the ability of blood to
      store energy of electron excitation that is produced in course of its own normal
      metabolism. From a practical point of view analysis of these qualities of blood
      may be a basement of new approach to diagnostic procedures.

PMID- 15244270
TI  - Biophotons from stressed and dying organisms: toxicological aspects.
AB  - Cells and organisms exposed to detrimental and toxic substances show different
      responses in photon emission dependent on amount, kind and exposure time of toxin
      as well as on the organism investigated. Radical reaction-generating substances
      and dehydrating, lipid dissolving and protein denaturating toxins which do not
      induce direct chemiluminescence resulting from reactive oxygen species were
      applied. Lethal doses of toxins and stress factors such as osmotics and
      temperature evoke increase in the intensity of photon emission resulting from a
      rapid and irreversible perturbation of homeostasis. Bacterial and fungal toxins
      that elicit hypersensitive death of plant cells or defense response correlated
      with photon emission are also briefly discussed. Collective molecular
      interactions contribute to the photon-generating degradative processes in
      stressed and dying organisms. The measurements of biophoton signals and analysis
      of their parameters are used to elucidate the possible mechanisms of the toxin
      organism interaction and the resistance of organisms. Toxicological perspectives
      of the use of these sensitive and rapid measurements as a part of direct toxicity
      assessment are discussed.

PMID- 15244271
TI  - Endogenous enzyme reactions closely related to photon emission in the plant
      defense response.
AB  - Lipoxygenase (LOX) and peroxidase (POD) reactions, which are involved in the
      production of reactive oxygen and radical species, are shown to be associated
      with ultraweak photon emission in plant defense mechanisms. These enzyme
      reactions induced high-level ultraweak photon emission in an in vitro reaction
      system. The application of LOX to sweet potato slices caused photon emission
      directly in plants. LOX substrate promoted photon emission in chitosan-treated
      sweet potato, and LOX inhibitor markedly suppressed this emission. Therefore, a
      LOX-related pathway, including LOX and other downstream reactions, is principally
      associated with photon emission in plant defense mechanisms.

PMID- 15244272
TI  - Variability of spectra of laser-induced fluorescence of colonic mucosa: its
      significance for fluorescence detection of colonic neoplasia.
AB  - To determine the extent of a natural variability of the spectra of the
      autofluorescence and its significance for a reproducibility of different
      approaches typically used in studies on fluorescence detection of colonic
      lesions. Two independent series of experiments have been conducted during three
      years in the same laboratory. Macroscopic tissue specimens obtained during
      operations of patients with colonic cancers were studied in vitro. The tissues
      were excited using UV lines of c.w. He-Cd laser and pulsed nitrogen laser and the
      autofluorescence spectra were recorded for areas visually diagnosed as normal or
      pathologically changed mucosa. Natural variability of the autofluorescence
      spectra of colonic tissues seems to be most important factor limiting sensitivity
      and specificity of the diagnostic algorithms. The mean fluorescence spectra
      obtained for normal mucosa and its neoplastic lesions differ significantly but
      the differences are difficult to observe because of the high natural variability
      among the individual spectra. Further studies of biological basis of the colonic
      autofluorescence are necessary for a progress in the field of fluorescence
      detection of colonic neoplastic lesions.

PMID- 15244273
TI  - Time-slot modulated electromagnetic fields of wireless communication systems: is
      there a health risk for man?
AB  - The safety guidelines of ICNIRP on bio-effects of low energy fields are based
      absorption and transformation into thermal effects. These guidelines are much
      higher than for acute reactions and long time exposure. It is pointed out that
      the guidelines for cordless telephone and mobile phone should correspond to long
      time exposure to low energetic electromagnetic fields.

PMID- 15244274
TI  - Quantum coherence of biophotons and living systems.
AB  - Coherence is a property of the description of the system in the classical
      framework in which the subunits of a system act in a cooperative manner.
      Coherence becomes classical if the agent causing cooperation is discernible
      otherwise it is quantum coherence. Both stimulated and spontaneous biophoton
      signals show properties that can be attributed to the cooperative actions of many
      photon-emitting units. But the agents responsible for the cooperative actions of
      units have not been discovered so far. The stimulated signal decays with non
      exponential character. It is system and situation specific and sensitive to many
      physiological and environmental factors. Its measurable holistic parameters are
      strength, shape, relative strengths of spectral components, and excitation curve.
      The spontaneous signal is non-decaying with the probabilities of detecting
      various number of photons to be neither normal nor Poisson. The detected
      probabilities in a signal of Parmelia tinctorum match with probabilities expected
      in a squeezed state of photons. It is speculated that an in vivo nucleic acid
      molecule is an assembly of intermittent quantum patches that emit biophoton in
      quantum transitions. The distributions of quantum patches and their lifetimes
      determine the holistic features of biophoton signals, so that the coherence of
      biophotons is merely a manifestation of the coherence of living systems.

PMID- 15244275
TI  - Single photon detectors for biology: present and future.
AB  - A summary of the status of present technology for the detection of single photons
      is presented with a view towards applications in biophotonics. Included are
      careful discussions of the numerous problems that can be encountered and how to
      get around them with the hope that this will be of help to biologists interested
      in doing work in the field of biophotonics. Emphasis is placed on traditional
      devices, but the field is one which is continuously developing and we review the
      status of new and very interesting technologies which are becoming available. The
      paper is meant to be fairly self-contained and assumes no extensive knowledge of
      the physics of photodetection.

PMID- 15244276
TI  - 'Virtual' photons as carriers of consciousness--a critical comment.

PMID- 15244277
TI  - Measurement of dynamic end-to-end cavity phase shifts in cesium-fountain
      frequency standards.
AB  - We have measured a previously unobserved systematic frequency shift in our cesium
      fountain frequency standard, NIST-F1. This shift, predicted theoretically
      previously, mimics the well-known end-to-end phase shift in atomic beam standards
      when synchronous thermal transients are present. Detuning the microwave cavity
      several megahertz from resonance reduces this effect to the deltaf/f = 1o(-16)
      level.

PMID- 15244278
TI  - Finite element modelling of nanostructured piezoelectric resonators (NAPIERs).
AB  - A new modification to the traditional piezoelectric thin film bulk acoustic wave
      resonator (FBAR) and solidly mounted acoustic wave resonator (SMR) is proven to
      significantly improve their performances. The proposed design involves the
      surface micro/nano structuring of planar piezoelectric thin films to realize an
      array of a large number of rod-like structures. In contrast to the plate-like
      thickness extensional resonance in traditional FBAR and SMR devices, the rod-like
      structures can be excited in their length extensional resonance, yielding a
      higher electromechanical coupling factor and effectively eliminating the spurious
      resonances from lateral modes of vibration. The designs have been investigated by
      two and three-dimensional finite element analyses and one-dimensional
      transmissionline modelling. The results show that significant increases in the
      electromechanical coupling factor of ca. 40% can be achieved by using the rod
      like length extensional resonances as compared with the plate-like thickness
      extensional resonances in traditional devices. Simulations show that rod width-to
      thickness aspect ratios of less than 0.5 could result in an electromechanical
      coupling factor (k2eff) of over 10% for a zinc oxide device, compared with
      approximately 7% for a conventional design.

PMID- 15244279
TI  - Fabrication of modified lead titanate piezoceramics with zero temperature
      coefficient and its application on SAW devices.
AB  - The Samarium-modified, lead titanate ceramics with a composition of
      (Pb0.67Ca0.15Sr0.06Sm0.08) (Ti0.98Mn0.02)O3 were prepared by conventional mixed
      oxide method. By properly varying the sintering and poling conditions, the
      samples with zero temperature coefficient of resonant frequency were fabricated.
      The piezoelectric and dielectric properties were measured; it showed that the
      samples with zero temperature coefficient still keep high-thickness,
      electromechanical coupling coefficient, kt (>0.55), and small planar
      electromechanical coupling coefficient, kp. Surface acoustic wave (SAW) filters
      were fabricated; and the properties, including phase velocity and
      electromechanical coupling coefficient, were measured. Microstructural and
      compositional analyses have been carried out using scanning electron microscopy
      and x-ray diffraction.

PMID- 15244280
TI  - Contact analysis and mathematical modeling of traveling wave ultrasonic motors.
AB  - An analysis of the contact layer and a mathematical modeling of traveling wave
      ultrasonic motors (TWUM) are presented for the guidance of the design of contact
      layer and the analyses of the influence of the compressive force and contact
      layer on motor performance. The proposed model starts from a model previously
      studied but differs from that model in that it adds the analysis of the contact
      layer and derives the steady-state solutions of the nonlinear equations in the
      frequency domain, rather than in the time domain, for the analyses of vibrational
      responses of the stator and operational characteristics of the motor. The maximum
      permissible compressive force of the motor, the influences of the contact layer
      material, the thickness of the contact layer, and the compressive force on motor
      performance have been discussed. The results show that by using the model, one
      can understand the influence of the compressive force and contact layer material
      on motor performance, guide the choice of proper contact layer material, and
      calculate the maximum permissible compressive force and starting voltage.

PMID- 15244281
TI  - An ultrasonic motor driven by the phase-velocity difference between two traveling
      waves.
AB  - This paper presents a new ultrasonic motor in which the rotor rotation speed is
      locked by the phase-velocity difference between the two traveling waves
      propagating on the stator and the rotor. First, the unique construction to excite
      two traveling waves both in the stator and the rotor is described. Then, the
      operation principle of the present motor is revealed by our careful experiments.
      Dynamics of the two traveling waves are measured by an in-plane laser Doppler
      vibrometer under various conditions, as well as the motor performances. Our
      experiments show that the rotation speed of the motor is equal to the phase
      velocity difference between the two traveling waves on the contact surfaces of
      rotor and stator. It is confirmed that the rotor rotates so as to cancel the
      phase-velocity difference between the traveling vibrations along the
      circumferences of the rotor and stator. If the load does not exceed the maximum
      torque that is determined by the vibration amplitude, the rotation speed is
      subject only to the phase-velocity difference.

PMID- 15244282
TI  - Development of an improved calibration method for the LFB ultrasonic material
      characterization system.
AB  - We investigated standard specimens for accurately calibrating the line-focus-beam
      ultrasonic material characterization (LFB-UMC) system without system
      dependencies. We evaluated several types of lithium tantalate (LiTaO3) substrates
      using two LFB-UMC systems with different device/system characteristics to measure
      and calibrate the propagation characteristics of the leaky surface acoustic waves
      (LSAWs), and analyzed the variations between the calibrated results. We concluded
      from this analysis that, by selecting materials with the cut surfaces and
      propagation directions of standard specimens that are identical to the objects to
      be calibrated, calibration errors resulting from different performance
      characteristics between the two systems could be nearly eliminated. Also,
      analytical errors caused by the effects of spectra with two close peaks (another
      propagation wave mode), one of the most common problems of characterization in
      the past, could be eliminated at the same time by this method.

PMID- 15244283
TI  - Elastic, dielectric, and piezoelectric losses in piezoceramics: how it works all
      together.
AB  - The quality factor along with electromechanical coupling coefficient (CEMC) is
      commonly used as a measure of the energy efficiency of a piezoelectric transducer
      (PT) working as an energy converter. Losses in piezoceramics are
      phenomenologically considered to have three coupled mechanisms: dielectric,
      elastic, and piezoelectric. Their cumulative performance first of all determines
      the PT quality factor characterizing the efficiency of vibrational energy
      accumulation, and related to it dissipative effects. The extended definition of
      the PT electromechanical quality factor (EMQ) with permanent energy exchange
      between electrical source of excitation and PT was proposed. The EMQ analysis has
      been conducted on the basis of complex material constants for both stiffened and
      unstiffened canonical vibrational modes. The efficiency of mechanically free and
      electrically excited piezoceramic transducers in a wide frequency range of PT
      harmonics, especially between the fundamental resonance and antiresonance
      frequencies, was investigated, and the effect of piezoelectric loss anomaly with
      extremely low total losses was predicted. Particularly, optimization of PT
      excitation with connected reactive (capacitive) element was conducted to provide
      higher PT mechanical vibrational characteristics with less total losses. The
      requirements to the piezoceramic material parameters, types of transducer
      vibrations, and especially to the piezoelectric loss factor in the range of
      physically valid values were established to provide maximal EMQ.

PMID- 15244284
TI  - Improved parametric imaging of scatterer size estimates using angular
      compounding.
AB  - The feasibility of estimating and imaging scatterer size using backscattered
      ultrasound signals and spectral analysis techniques was demonstrated previously.
      In many cases, size estimation, although computationally intensive, has proven to
      be useful for monitoring, diagnosing, and studying disease. However, a difficulty
      that is encountered in imaging scatterer size is the large estimator variance
      caused by statistical fluctuations in echo signals from random media. This paper
      presents an approach for reducing these statistical uncertainties. Multiple
      scatterer size estimates are generated for each image pixel using data acquired
      from several different directions. These estimates are subsequently compounded to
      yield a single estimate that has a reduced variance. In this feasibility study,
      compounding was achieved by translating a sectored-array transducer in a
      direction parallel to the acquired image plane. Angular compounding improved the
      signal-to-noise ratio (SNR) in scatterer size images. The improvement is
      proportional to the square root of the effective number of statistically
      independent views available for each image pixel.

PMID- 15244285
TI  - Linear approach to axial resolution in elasticity imaging.
AB  - Thus far axial resolution in elasticity imaging has been addressed only
      empirically. No clear analytical approaches have emerged because the estimator is
      non-linear in the data, correlation functions are nonstationary, and system
      responses vary spatially. This paper describes a linear systems approach based on
      a small-strain impulse approximation that results in the derivation of a local
      impulse response (LIR) and local modulation transfer function (LMTF). Closed-form
      solutions for strain LIR are available to provide new insights on the role of
      instrumentation and processing on axial strain resolution. Novel phantom
      measurements are generated to validate results. We found that the correlation
      window determines axial resolution in most practical situations, but that the the
      same system properties that determine B-mode resolution ultimately limit
      elasticity imaging.

PMID- 15244286
TI  - Controlled ultrasound tissue erosion.
AB  - The ability of ultrasound to produce highly controlled tissue erosion was
      investigated. This study is motivated by the need to develop a noninvasive
      procedure to perforate the neonatal atrial septum as the first step in treatment
      of hypoplastic left heart syndrome. A total of 232 holes were generated in 40
      pieces of excised porcine atrial wall by a 788 kHz single-element transducer. The
      effects of various parameters [e.g., pulse repetition frequency (PRF), pulse
      duration (PD), and gas content of liquid] on the erosion rate and energy
      efficiency were explored. An Isppa of 9000 W/cm2, PDs of 3, 6, 12, and 24 cycles;
      PRFs between 1.34 kHz and 66.7 kHz; and gas saturation of 40-55% and 79-85% were
      used. The results show that very short pulses delivered at certain PRFs could
      maximize the erosion rate and energy efficiency. We show that well-defined
      perforations can be precisely located in the atrial wall through the controlled
      ultrasound tissue erosion (CUTE) process. A preliminary in vivo experiment was
      conducted on a canine subject, and the atrial septum was perforated using CUTE.

PMID- 15244287
TI  - Measurement of the material properties of viscous liquids using ultrasonic guided
      waves.
AB  - The theoretical basis for a testing tool in the form of a circular waveguide for
      measuring both the dynamic viscosity and the longitudinal bulk velocity of
      viscous liquids is presented. It is based on the measurements of the attenuation
      of the fundamental torsional mode, T(0,1), and the fundamental longitudinal mode,
      L(0,1), of the waveguide when immersed in the liquid. The modeling techniques to
      extract the shear viscosity and the longitudinal bulk velocity are explained and
      experimentally verified. Results for two viscous liquids are presented: good
      agreement between theory and experiment was obtained.

PMID- 15244288
TI  - Evaluation of mass-produced commercial LiTaO3 single crystals using the LFB
      ultrasonic material characterization system.
AB  - A mass-production line of lithium tantalate (LiTaO3) crystals with a maximum
      charge number of 60 for surface acoustic wave (SAW) devices was evaluated with
      the line-focus-beam (LFB) ultrasonic material characterization system. Some
      serious problems associated with chemical compositions were observed and resolved
      by measuring the velocities of Rayleigh-type leaky surface acoustic waves
      (LSAWs), VLSAW, for two groups of LiTaO3 wafers: 21 36 degrees Y X-LiTaO3 wafers
      selected randomly from crystal ingots grown with different charge numbers in
      different furnaces, and 14 42 degrees Y X-LiTaO3 wafers obtained at the top,
      middle, and bottom parts from 5 crystals selected from 39 crystals grown
      successively in the same furnace and crucible. Using the measured VLSAW and the
      predetermined relationship between VLSAW and Li2O concentrations, M(Li2O), we
      estimated the average M(Li2O) controlled in the current mass-production line to
      be about 48.77 mol% with a maximum difference of 0.75 mol%. The composition for
      each crystal ingot increased linearly about 0.04 mol% from the top to the bottom,
      and no dependence on the charge number was observed, as the melt composition used
      for the mass production was controlled through Curie temperature (TC)
      measurements. A nearly true congruent composition of 48.49 Li2O-mol% was obtained
      through the precise VLSAW data for the 42 degrees Y X-LiTaO3 wafers, that was
      about 0.3 mol% less than the melt composition in the production line. It was also
      pointed out that the TC measurement conditions, including room temperatures
      surrounding the measurement systems, should be re-examined for reliable
      production control. A guideline for more efficient mass production of the
      crystals has been established concerning the true congruent composition as the
      starting material.

PMID- 15244289
TI  - Directional scholte wave generation and detection using interdigital capacitive
      micromachined ultrasonic transducers.
AB  - Directional generation and detection of Scholte waves and other guided modes in
      liquids and microfluidic channels by capacitive micromachined ultrasonic
      transducers (cMUTs) is reported. An interdigital transducer structure along with
      a phased-excitation scheme is used to enhance the directionality of Scholte
      interface waves in microfluidic environments. Finite element models are developed
      to predict the performance of the devices in both fluid half-spaces and
      microchannels. Experiments on the interdigital cMUTs show that a five-finger-pair
      device in a water half-space has 12 dB of directionality in generating Scholte
      waves at the design frequency of 10 MHz. A 10-finger device operating at 10 MHz
      in a water-filled microchannel has 13.4 dB of directionality. These
      directionality figures agree well with the modeling results. Using the results of
      the finite element model of a cMUT in a fluid half-space, it was determined that
      41% of the acoustic power radiated into the fluid is contained in the Scholte
      wave propagating in the desired lateral direction. Transducers are demonstrated
      to perform bidirectional pumping in fluid channels with input power levels in the
      milliwatt range. Interdigital cMUTs fabricated using low temperature processes
      can be used as compact ultrasonic transducers with integrated electronics for
      sensing and actuation in fluidic environments.

PMID- 15244290
TI  - A direct energy balance method for approximating envelope decay of oscillating
      MEMS structures.
AB  - The real pole component (envelope decay coefficient) of an oscillating
      microelectromechanical systems (MEMS) structure is calculated directly in the
      energy domain without using an equation of motion. Similar to the simplified
      Rayleigh frequency calculation in which maximum potential and kinetic energy are
      equated, our method equates the initial minus dissipated energy to present
      energy.

PMID- 15244291
TI  - Signs of life. Capital markets may jumpstart once-stagnant assisted living
      sector.

PMID- 15244292
TI  - Where do we go from here?

PMID- 15244293
TI  - Advice from the experts. Tips for assisted living executives.

PMID- 15244294
TI  - Uncle Sam at your service. Securing public funding has pitfalls and drawbacks,
      but the socio-economic benefits can make all the hard work worthwhile.

PMID- 15244295
TI  - Splish splash... Adding alcohol-based handrubs to hand hygiene routines
      contributes to patient safety, saves lives and adds to operational efficiency.

PMID- 15244296
TI  - The history of interventional ultrasound.
AB  - Ultrasound has been used to guide interventional procedures for more than 30
      years. Initial applications included biopsy techniques and simple aspiration of
      fluid collections. However, with improved sonographic imaging and the use of
      different ultrasonic probes as well as development of less invasive therapies,
      there has been an increase in the use of ultrasound to guide interventional
      procedures. Interventional ultrasound has become routine in most medical
      specialties. Because of the remarkable success of interventional procedures
      guided by sonography, combined with an outstanding safety record, there is no
      doubt that there will be a future increase in the number and types of
      interventional procedures performed under sonographic guidance.

PMID- 15244297
TI  - Transvaginal color Doppler sonography versus sonohysterography in the diagnosis
      of endometrial polyps.
AB  - OBJECTIVE: To compare the diagnostic performance of transvaginal color Doppler
      sonography (TVCD) and sonohysterography (SHG) in the diagnosis of endometrial
      polyps. METHODS: Fifty-one women (mean age, 51 years; range, 27-75 years) with
      clinical or B-mode sonographic suspicion of endometrial polyps were included in
      this prospective study. Transvaginal color Doppler sonography first and then SHG
      were performed in all patients. On TVCD, a polyp was suspected when a vascular
      pedicle penetrating the endometrium from the myometrium was identified. On SHG, a
      polyp was suspected when a focal polypoid lesion was seen within the endometrial
      cavity. All patients underwent hysteroscopy and endometrial biopsy, the findings
      of which were used as the criterion standard. Sensitivity and specificity for
      TVCD and SHG were calculated and compared by the McNemar test. RESULTS:
      Hysteroscopy and endometrial biopsy findings were as follows: endometrial polyps,
      41; endometrial hyperplasia, 3; cystic atrophy, 4; proliferative endometrium, 2;
      and endometritis, 1. Sensitivity and specificity for TVCD and SHG were 95% and
      80% and 100% and 80%, respectively (McNemar test, P = .5) CONCLUSIONS:
      Transvaginal color Doppler sonography and SHG had similar performance for
      diagnosing endometrial polyps.

PMID- 15244298
TI  - Accuracy of diagnosis of retained products of conception after dilation and
      evacuation.
AB  - OBJECTIVE: Uterine re-evacuation samples taken in cases of suspected residua
      after curettage are occasionally negative for gestational tissue. We aimed at
      evaluating the occurrence of such postcurettage re-evacuation-negative samples
      and at exploring factors that may influence their occurrence. METHODS: This was a
      cross-sectional comparative retrospective study of 69 consecutive women who
      underwent uterine re-evacuation for suspected postcurettage gestational remnants.
      Pathologic reports of samples drawn during re-evacuations were reviewed to
      determine whether the extracted tissue contained gestational tissue. The presence
      of factors that may influence the rate of a positive or negative sample (eg,
      sonographic findings, gestational age at initial procedure, and presenting
      symptom) was noted and compared between women with and without histologically
      verified remnants. RESULTS: Twenty-eight (41%) of the re-evacuation samples were
      histopathologically positive for gestational remnants. Residual tissue was more
      commonly found when the initial evacuation was performed at a more advanced
      gestational age (> 15 weeks). Women referred by emergency department attendants
      had significantly fewer positive samples. Normal expert sonographic examination
      practically excluded yielding samples. Conversely, no negative samples were
      preceded by sonographic reports mentioning residua. CONCLUSIONS: Most re
      evacuation samples taken during a re-evacuation procedure for suspected residua
      are negative for gestational tissue. Parameters that are likely related to
      histologically confirmed gestational residual tissue are advanced gestational age
      at initial evacuation, level of the sonographer's skill, persistent bleeding as
      the presenting symptom, and a sonographic report specifically mentioning retained
      gestational tissue.

PMID- 15244299
TI  - First-trimester sonographic diagnosis of holoprosencephaly: value of the
      "butterfly" sign.
AB  - OBJECTIVE: To study the value of choroid plexus dysmorphology as a screening tool
      for the first-trimester sonographic diagnosis of holoprosencephaly in a high-risk
      population. METHODS: A total of 378 consecutive pregnancies undergoing chorionic
      villus sampling between 11 and 14 weeks' gestation were scanned before the
      procedure, following the recommendations of the Fetal Medicine Foundation
      (London, England). A cross-sectional view of the fetal brain, including the
      visualization of both choroid plexuses (the "butterfly" sign), was obtained in
      all cases. RESULTS: There were 3 cases in which the butterfly sign was not
      identified. In these cases, the first-trimester diagnosis of holoprosencephaly
      was confirmed by the presence of a single monoventricular cavity and fused
      thalami. Two of these fetuses had features of facial dysmorphism at the time of
      presentation and 2 had extracranial anomalies, including a cystic hygroma in 1
      and a small omphalocele and polydactyly in another. Chromosomal analysis showed
      trisomy 13 in 2 cases and a ring chromosome 13 in the other. CONCLUSIONS: This
      series suggests that failure to identify the butterfly sign is a warning sign of
      holoprosencephaly in the first trimester. Systematic identification of the
      butterfly sign at the time of sonographic assessment of nuchal translucency
      provides a valuable tool for the early screening of holoprosencephaly.

PMID- 15244300
TI  - Sonographic diagnosis of urethral anomalies in infants: value of perineal
      sonography.
AB  - OBJECTIVE: To assess the value of urethral sonography including a perineal
      approach in evaluating urethral anomalies in infants. METHODS: A radiology
      database review identified 88 patients (mean age +/- SD, 64 +/- 84 days) who
      underwent voiding cystourethrography (VCUG) and urethral sonography as part of
      extended sonography of the urinary tract. Sonographic and VCUG images and reports
      were reviewed to assess agreement between both modalities for detection of
      urethral anomalies. RESULTS: Sonography facilitated the correct diagnosis of all
      3 posterior urethral valves. The only urethral diverticulum, the only ectopic
      ureteric insertion into the urethra, the only urogenital sinus, and the only
      urethrovaginal fistula were also shown on sonography. In 73 (94%) of 78 cases,
      sonography correctly showed the absence of anomalies. In 5 infants, sonography
      could not reliably assess the urethra and showed indirect signs of urethral
      anomalies; however, these patients had normal urethras on VCUG. CONCLUSIONS: Our
      data show that sonography of the urethra is a valuable tool for diagnosis of
      urethral anomalies. Especially, negative findings on sonography are highly
      suggestive of the absence of urethral anomalies. Positive or equivocal
      sonographic findings should indicate VCUG.

PMID- 15244301
TI  - Utility and safety of ultrasound-guided fine-needle aspiration of salivary gland
      masses including a cytologist's review.
AB  - OBJECTIVE: To evaluate the utility and safety of ultrasound-guided fine-needle
      aspiration of the salivary glands for diagnosis of focal masses in the salivary
      glands, including the prevalence of nondiagnostic sampling, the impact of the
      presence of a cytologist during the procedure, and the usefulness of flow
      cytometry. METHODS: A retrospective analysis of 43 ultrasound-guided fine-needle
      aspirations of the salivary glands from 36 lesions in 33 patients was performed.
      Fine-needle aspirations were obtained under sonographic guidance, and 1 to 6
      punctures were made with 20- to 25-gauge needles. Ultrasound-guided fine-needle
      aspirations obtained in the presence of a cytologist were compared with those
      performed without a cytologist regarding the adequacy of the specimen and the
      number of punctures performed. Postprocedural complications and the frequency
      with which flow cytometry was performed were noted. Cytopathologic diagnosis was
      correlated with clinical follow-up (n = 33) and surgical pathologic findings (n =
      10). RESULTS: Cytologic diagnosis was made in 31 (94%) of 33 patients, confirming
      a neoplastic process in 18 (50%) of 36 and a non-neoplastic process in 16 (44%)
      of 36. Although the presence of a cytologist at the bedside resulted in a higher
      prevalence of diagnostic sampling (P < .05), it did not alter the number of
      punctures performed (mean, 3 punctures). No complications were encountered except
      for pain in 2 patients. Flow cytometry was helpful in 8 (22%) of 36 patients.
      CONCLUSIONS: Ultrasound-guided fine-needle aspiration of the salivary glands is a
      safe procedure with a low prevalence of nondiagnostic sampling. Approximately 44%
      of patients can be spared surgical intervention through diagnosis of a non
      neoplastic process. The presence of a cytologist increases the likelihood of
      obtaining a diagnostic sample. Flow cytometry was helpful in 22% of patients.

PMID- 15244302
TI  - Diagnosis of intracranial dural arteriovenous fistulas by carotid duplex
      sonography.
AB  - OBJECTIVE: To validate carotid duplex sonography (CDS) in diagnosis of
      intracranial dural arteriovenous fistulas (AVFs) against the standard of cerebral
      catheter angiography. METHODS: We investigated 35 patients with dural AVFs and 64
      patients without dural AVFs confirmed by the catheter angiographic studies.
      Twenty CDS parameters in 4 categories, including resistive index (RI), flow
      volume, peak systolic velocity, and end-diastolic velocity, were evaluated.
      Abnormal CDS findings were defined as the data above 95th percentile or below 5th
      percentile values from 180 control subjects. We determined the sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      in each CDS parameter. RESULTS: The parameter of RI of the external carotid
      artery (ECA; cutoff points: right, 0.72; left, 0.71) yielded the highest
      sensitivity (74%), specificity (89%), positive predictive value (79%), negative
      predictive value (86%), and accuracy (84%) for predicting dural AVFs. All other
      ECA-related parameters yielded sensitivity lower than 70%, and those related to
      the internal carotid artery were lower than 30%. The sensitivity values for the
      parameter of RI of the ECA in different locations of dural AVFs were 54% (7 of 13
      patients) in cavernous sinus dural AVFs and 86% (19 of 22 patients) in non
      cavernous sinus dural AVFs (P = .05). CONCLUSIONS: The RI of the ECA is the best
      CDS parameter for predicting intracranial dural AVFs. Carotid duplex sonography
      can be used as the initial screening tool for diagnosis in patients having
      symptoms related to dural AVFs.

PMID- 15244303
TI  - Residents should not independently perform focused abdominal sonography for
      trauma after 10 training examinations.
AB  - OBJECTIVES: To assess whether 10 focused abdominal sonography for trauma (FAST)
      examinations could be used as a minimum standard for training, as suggested
      previously. METHODS: This was a retrospective review of patients with abdominal
      trauma who underwent resident-performed FAST examinations before surgical or
      Department of Radiology evaluation. RESULTS: Six hundred ninety-eight patients
      were examined by resident-performed FAST followed by reference standard
      evaluations. Four hundred twelve patients were evaluated by residents who
      previously performed 10 FAST examinations; 154 were evaluated by 29 residents
      performing their 11th through 30th examinations; and 258 were evaluated by 10
      residents performing their 31st and subsequent examinations. The results of
      resident-performed FAST for intraperitoneal free fluid were as follows: 11 to 20
      examinations--sensitivity, 73.9% (95% confidence interval, 51.3%-88.9%);
      specificity, 98.8% (92.5%-99.9%); true-positive findings, 17; true-negative, 81;
      false-positive, 1; false-negative, 6; total patients, 105; 21 to 30 examinations-
      sensitivity, 100% (73.2%-100%); specificity, 97.1% (83.3%-99.9%); true-positive,
      14; true-negative, 34; false-positive, 1; false-negative, 0; total patients, 49;
      31 and more examinations--sensitivity, 94.8% (88.6%-97.9%); specificity, 98.6%
      (94.5%-99.8%); true-positive, 110; true-negative, 140; false-positive, 2; false
      negative, 6; total patients, 258. CONCLUSIONS: The suggestion that 10
      examinations could be used as a minimum standard for training in FAST
      examinations was not validated.

PMID- 15244304
TI  - Sonographic duplication artifact of the spinal cord in infants and children.
AB  - OBJECTIVE: To describe the features of sonographic duplication artifacts that we
      have occasionally seen when imaging the spinal cord of infants and children,
      mostly with postrepair myelomeningocele. METHODS: Sonography of the spine was
      performed for the evaluation of neonates with suspected spinal cord abnormalities
      and of older children in the follow-up of postrepair open-spine defects. RESULTS:
      Each of our patients had a single spinal cord, but the duplication artifact was
      seen with 2 brands of scanners and with both linear array and vector array
      transducers. CONCLUSIONS: The finding of duplication artifacts when imaging the
      spinal cord of infants and children should be recognized as such and should not
      be misinterpreted as representing diastematomyelia or diplomyelia.

PMID- 15244305
TI  - Imaging of adnexal masses in pregnancy.
AB  - OBJECTIVE: To illustrate the imaging appearances of a variety of adnexal masses
      in pregnancy. METHODS: Cases of adnexal masses in pregnancy were chosen to
      illustrate the appearance on ultrasonography and magnetic resonance imaging.
      RESULTS: Adnexal masses in pregnancy have a wide spectrum of imaging
      characteristics and clinical manifestations. Sonography is important in
      diagnosing, monitoring, and determining the malignant potential of these masses.
      Common adnexal lesions seen in pregnancy include simple cysts, hemorrhagic cysts,
      leiomyomas, and hyperstimulated ovaries in patients who have undergone assisted
      fertility. Uncommon adnexal lesions specific to pregnancy include hyperreactio
      luteinalis, theca lutein cysts with moles, and luteomas. Adnexal masses
      associated with pain include ovarian torsion and heterotopic pregnancy. Adnexal
      lesions that are found incidentally include teratomas, endometriomas,
      hydrosalpinx, cystadenomas, and cystadenocarcinomas. When the diagnosis of the
      adnexal mass cannot be made on the basis of sonographic appearance alone,
      magnetic resonance imaging may help. CONCLUSIONS: Familiarity with the
      clinicopathologic and sonographic features of common and uncommon adnexal masses
      in pregnancy is important for diagnosis and treatment.

PMID- 15244306
TI  - Angiographic power 3-dimensional quantitative analysis in gynecologic solid
      tumors: feasibility and reproducibility.
AB  - OBJECTIVE: To determine the reproducibility of a simplified method of power
      Doppler 3-dimensional (3D) sonographic examination. METHODS: Twenty-nine patients
      with solid pelvic masses underwent transvaginal 3D power Doppler evaluation. The
      volume of interest was obtained by drawing the margins of the largest section of
      the mass in the 3 orthogonal planes. The 3D vascular parameters ("relative
      color," "average color," and "flow measure") obtained by our method were compared
      with those calculated by a manufacturer-suggested model based on several parallel
      section planes drawn on the longitudinal frames. The intraobserver variability
      was quantified on 5 different 3D images acquired by the same operator at 5-minute
      intervals for each patient. The intraobserver variability was also assayed in 10
      patients at 24-hour intervals. Ten patients were scanned by a second sonographer
      for interobserver variability. RESULTS: There was high agreement between the 3D
      parameters obtained with the 2 methods. The 3D indices were similar in repeated
      observations at 5-minute intervals (median coefficients of variation for relative
      color, average color, and flow measure, 10.9, 4.5, and 13.0, respectively) and at
      24-hour intervals (intraclass correlation coefficients for relative color,
      average color, and flow measure, 0.920, 0.978, and 0.978) and by the second
      sonographer (interclass correlation coefficients for relative color, average
      color, and flow measure, 0.978, 0.966, and 0.997). CONCLUSIONS: The acceptable
      rates of intraobserver and interobserver variability make this approach
      potentially suitable for research protocols.

PMID- 15244307
TI  - Evaluation of lymph node perfusion using continuous mode harmonic ultrasonography
      with a second-generation contrast agent.
AB  - OBJECTIVE: To evaluate the contribution of continuous mode contrast-enhanced
      harmonic ultrasonography (CE-HUS) with a second-generation contrast agent to the
      characterization of superficial lymphadenopathies with respect to conventional
      ultrasonographic techniques (B-mode and power Doppler). METHODS: Fifty-six lymph
      nodes from 45 patients were studied both by conventional techniques and by CE
      HUS. The dimensions, intranodal architecture, margins, and location of vessels
      were evaluated. Subsequently, all the lymph nodes were examined by CE-HUS, and
      enhancement of echogenicity was evaluated. The diagnoses obtained by means of
      fine-needle aspiration cytologic examination, surgical biopsy, or both were
      compared with those obtained by ultrasonography. RESULTS: Of the lymph nodes
      examined, 30 were benign and 26 were malignant (18 metastases and 8 non-Hodgkin
      lymphomas). The study using CE-HUS showed intense homogeneous enhancement in 28
      of 30 reactive lymph nodes; perfusion defects in 17, of which 15 were neoplastic
      and 2 were inflammatory; intense but inhomogeneous speckled enhancement in the
      early arterial phase in 5 cases of lymphoma; and, last, scarce or absent
      intranodal enhancement in 4 metastases. The specificity, sensitivity, and
      accuracy of conventional techniques in differentiation between benign and
      malignant lymph nodes were 76%, 80%, and 78% versus 93%, 92%, and 92.8% for CE
      HUS. The increase in correct diagnoses was significant (P = .05) when
      conventional ultrasonography was tested against CE-HUS. CONCLUSIONS: Superficial
      lymph nodes can be characterized as being neoplastic or benign with a high degree
      of diagnostic accuracy on the basis of the perfusion characteristics evaluated by
      CE-HUS. This technique has been shown to afford a higher degree of accuracy than
      currently obtainable by any other ultrasonographic technique.

PMID- 15244308
TI  - Increased through-transmission in abdominal tuberculous lymphadenitis.
AB  - OBJECTIVE: To describe 2 cases of abdominal tuberculosis in which sonographic
      evaluation of mesenteric lymphadenopathy showed increased through-transmission
      suggestive of caseating necrosis. METHODS: Two patients with abdominal pain and
      other symptoms (including fever, diarrhea, and weight loss) underwent abdominal
      sonography with a 6-MHz curved array transducer. One patient also underwent
      sonographically guided fine-needle aspiration of multiple lymph nodes, and the
      other underwent computed tomography, colonoscopy, and colon biopsy. RESULTS: In
      both patients, sonography showed multiple rounded hypoechoic lesions with
      increased ultrasound through-transmission suggestive of necrotic lymphadenopathy.
      No color flow was shown. In 1 case, the posterior acoustic enhancement was
      accentuated in the harmonic imaging mode. In the other case, the lesions shown on
      sonography corresponded to computed tomographic findings of low-density lymph
      nodes. Results of fine-needle aspiration and colon biopsy were positive for
      tuberculosis. CONCLUSIONS: Posterior acoustic enhancement in abdominal
      lymphadenopathy can suggest the diagnosis of tuberculous lymphadenitis. Detection
      of this finding is facilitated by scanning in the harmonic mode. Necrotic nodes
      will lack color flow and can be distinguished from lymphadenopathy of other
      causes. Sonography can also be used for fine-needle aspiration of necrotic nodes
      to yield a definitive diagnosis.

PMID- 15244309
TI  - Color Doppler sonographic findings of inflamed and perforated Meckel
      diverticulum.
AB  - OBJECTIVE: To describe color Doppler sonographic findings in 2 cases of inflamed
      and perforated Meckel diverticulum. METHODS: Two patients with inflamed and
      perforated Meckel diverticulum underwent color Doppler sonographic studies.
      RESULTS: Gray scale sonographic examination identified a fixed cystlike structure
      with a gut signature surrounded by a hyperechoic layer. Color Doppler sonography
      revealed hyperemia in the diverticular wall and hyperechoic layer, which was more
      intense in 1 patient. CONCLUSIONS: Identification of a fixed cystlike structure
      with a gut signature and wall hyperemia suggests the diagnosis of inflamed Meckel
      diverticulum; when a hyperechoic layer surrounds this structure, perforation of
      the diverticulum should be suspected.

PMID- 15244310
TI  - Intrathoracic postesophagectomy stomach: the role of chest sonography in
      pediatric patients.
AB  - OBJECTIVE: Sonography is a reliable imaging tool, complementary to plain
      radiography in certain pediatric chest disorders. It can assist in localizing and
      characterizing mediastinal, pleural, and pulmonary opacities. We have found that
      sonography is also valuable in elucidating postoperative chest radiography. In
      this series, our objective was to assess the value of sonography for
      understanding the radiologic changes in the child after esophagectomy and to
      highlight its ability to show the intrathoracic stomach. METHODS: Sonography was
      performed with a 5- to 12-MHz linear array transducer via anterior, lateral, and
      posterior intercostal approaches of the abnormal hemithorax in supine, prone,
      and, when necessary, upright positions. RESULTS: The distended fluid- or food
      filled stomach was identified on sonography as the source of the undefined
      thoracic opacity on plain radiography in 2 patients. CONCLUSIONS: The
      postoperative pediatric chest radiograph is often difficult to understand.
      Sonography can differentiate between lung consolidation or pleural fluid and a
      food- or fluid-filled stomach. Simple maneuvers such as postural changes can
      confirm in the diagnosis.

PMID- 15244311
TI  - Prenatal sonographic diagnosis of hemivertebra.
AB  - OBJECTIVE: To describe our experience in prenatal diagnosis of hemivertebra.
      METHODS: This is a case series of patients referred to our tertiary medical
      center over a 3-year period. All fetuses were scanned by high-resolution real
      time scanners. The apparent vertebral anomaly was assessed in a real-time manner
      by a joint team of obstetricians, sonographers, and pediatric orthopedic
      surgeons. A complete anomaly survey of other fetal organs was performed on each
      fetus. All patients were given proper counseling by the same joint team. All
      patients had detailed obstetric and neonatal follow-up. Prenatal sonograms,
      neonatal medical records, and clinical courses were evaluated retrospectively.
      RESULTS: During the 3 years, 6 cases of hemivertebra were identified in our
      department. Gestational age at diagnosis was 14 to 23 weeks. Two patients had
      conception by assisted reproductive technology. Associated anomalies included
      VATER syndrome (vertebral defects, imperforate anus, tracheoesophageal fistula,
      and radial and renal dysplasia), gastroschisis, and pyelectasis. Outcomes in
      fetuses without major associated anomalies were fair. CONCLUSIONS: Diagnosis of
      isolated hemivertebra might be associated with a favorable outcome. The 3 key
      factors in achieving an optimal spine at maturity, early diagnosis, anticipation,
      and prevention of deterioration, might be enhanced by our joint multidisciplinary
      approach to the diagnosis of skeletal anomalies.

PMID- 15244312
TI  - Sonographic diagnosis in iatrogenic entrapment of a femoropopliteal bypass graft.

PMID- 15244313
TI  - Sonography of acute appendicitis in a 9-month-old infant.

PMID- 15244314
TI  - Sonographic diagnosis of a serous tumor of low malignant potential of the
      fallopian tube.

PMID- 15244315
TI  - Fetal Dandy-Walker malformation complicated by late third-trimester unilateral
      intraventricular hemorrhage.

PMID- 15244316
TI  - Three-dimensional sonographic diagnosis of a large cystic neck lymphangioma.

PMID- 15244317
TI  - Calcipotriol cream in the treatment of flexural psoriasis.
AB  - In patients with psoriasis, 2-6% suffer from flexural psoriasis. Areas where
      flexural psoriasis is found are the axillae, groin, submammary region, perianal
      region, and retroauricular fold. Eleven patients with flexural psoriasis were
      enrolled in this study: six men and five women, aged between 5 and 55 years. All
      patients had common psoriasis presented with psoriatic lesions involving the
      axillae, groin and submammary region. Each patient was instructed to apply
      calcipotriol 50 microg/gm twice daily for 6 weeks. The treatment assessment,
      based on changes in erythema, scaling and thickness scores, was carried out at 2,
      4 and 6 weeks. The overall assessment of our cases in this study showed a marked
      and significant improvement in the treated intertriginous areas. The mean scores
      of erythema, scaling and thickness before treatment were 2.7, 2.3 and 2.5,
      respectively. There was a marked and dramatic improvement in seven patients
      (63.6%) within the first 2 weeks in which the response was more significant than
      other nonintertriginous psoriatic lesions. At the end of treatment, 10 patients
      (91%) showed complete clearance, and the mean scores were reduced to 0. One
      patient showed only moderate improvement. No significant adverse effect was
      reported. In conclusion, calcipotriol cream is effective, safe and well tolerated
      in the treatment of flexural psoriasis. Because tar preparations and anthralin
      are irritants and potent steroids are absorbed more in these areas, calcipotriol
      cream could be a better choice for the treatment of these cases.

PMID- 15244318
TI  - Low-power laser in osteoarthritis of the cervical spine.
AB  - Patients with symptomatic osteoarthritis of the cervical spine were treated with
      very low-power modulated laser (LPL). Two applications were performed at an
      interval of 20 days. Changes in pain and ultrasound thickness of the soft
      connective tissue layer above the right and the left superior trapezium were
      studied. No worsening of pain was observed. Pain improved after the first
      application of LPL in 9 out of 14 patients, but the difference was not
      significant. Pain improvement remained stable between the first assessment and
      the second assessment, which was performed after 20 days. In comparison with the
      first application, at the second application the number of patients with improved
      pain after LPL increased to 12 out of 14 (p < 0.01). An appreciable difference in
      the thickness of the subcutaneous soft tissue layer overlying the two superior
      trapezia was demonstrated in all patients at the first examination. Comparison of
      the measurements before and after the application of LPL showed significant
      differences.

PMID- 15244319
TI  - Bound thrombin-induced upregulation of myosin heavy chain isoform, SMemb
      messenger RNA expression in cultured rabbit vascular smooth muscle cells.
AB  - To investigate whether bound thrombin can induce modulation of SMemb expression
      in vascular smooth muscle (VSM) cells, messenger RNA (mRNA) expression was
      measured by in situ hybridization (ISH) and reverse transcription-polymerase
      chain reaction (RT-PCR) in cultured rabbit aortic VSM cells. To test the
      concentration- and time-dependent effect of bound thrombin on the expression of
      SMemb, confluent VSM cells were incubated for 48 h in 10% FBS-DMEM containing 0,
      3, 10 and 30 units/ml of bound thrombin. In addition, the confluent VSM cells
      were incubated for 6, 12, 24 and 48 h in 10% FBS-DMEM containing 10 units/ml of
      bound thrombin. Consequently, bound thrombin significantly increased SMemb mRNA
      in a concentration- and time-dependent manner. When compared with the effect of
      rabbit fibrinogen (10 microg/ml) and native thrombin (10 units/ml), SMemb mRNA
      was significantly increased by bound thrombin and was slightly increased by
      native thrombin, but not by fibrinogen. Other myosin heavy chain (MHC) isoform
      (SM1 and SM2) mRNA expressions were not changed by fibrinogen, native thrombin or
      bound thrombin. ISH revealed that there was no significant difference in the
      expression of MHC mRNAs among fibrinogen, native thrombin or bound thrombin.
      Western blot analysis demonstrated that the SMemb protein level was significantly
      increased by 2.5-fold by bound thrombin. When the clot-forming activities in
      cultured medium containing native thrombin or bound thrombin were measured from
      0.5 to 48 h, the activity of bound thrombin declined more slowly than that of
      native thrombin. In conclusion, bound thrombin could upregulate the expression of
      SMemb mRNA and protein in cultured VSM cells and the activity of bound thrombin
      was maintained for longer than that of native thrombin in culture medium.

PMID- 15244320
TI  - Power Doppler analysis of tendon vascularization.
AB  - Forty-nine patients with tendonitis (patellar in 16, quadriceps in two, Achilles
      in 12, rotator cuff disease in 19) and 47 patients with tenosynovitis (acute
      tenosynovitis in 25, stenosing tenosynovitis in 22) underwent ultrasound (US) and
      Power Doppler (PD)-US examination. Spectral analysis of flow signals was
      performed in all patients. Ten patients (six with tendonitis, four with
      tenosynovitis) were rewired after medical therapy. Six healthy volunteers were
      also examined for control purposes. Three different patterns of flow distribution
      were found in patients with tendonitis and active tenosynovitis. The vessels of
      tendons without tendon sheaths began with great peduncles at the level of the
      peritendinous soft tissues and were then distributed inside the tendon (pattern
      I). A clear peritendinous hypervascular pattern was found in all active
      tenosynovitis, but no vessels were found inside the tendons (pattern II). In some
      cases of intratendinous or partial lesions PD-US revealed some vessels located
      near or inside the lesion (pattern II). On spectral analysis these vessels
      corresponded to arteries with a low resistance index or small venules. PD-US
      revealed a significant reduction of flow signals in patients rewired after
      medical therapy. No pathological flow signals were found either in patients with
      stenosing tenosynovitis or in the control group. PD-US gives us an in vivo
      confirmation of tendon vascularity. Spectral analysis adds further information to
      gray-scale US.

PMID- 15244321
TI  - Assessment of residual immunoreactivity in red or white wines clarified with pea
      or lupin extracts.
AB  - Vegetable proteins could be a suitable alternative to animal proteins in the
      clarification of wine, but their residues could represent a risk for subjects
      with food allergy or intolerance. The aim of this study was to investigate the
      presence of specific immunoreactivity in red and white wines treated, as must or
      wine, with vegetable proteins in the clarification process. The proteins
      considered were prepared from lupins and peas, which are not included among the
      allergens listed in annex Illbis of Directive 2003/89/EC. The presence of
      residual immunoreactivity to specific rabbit anti-lupin and anti-pea polyclonal
      antibodies in treated wines was assessed by electrophoresis (SDS-PAGE) and
      immunoblotting. Residual protein was not detectable in red wines clarified with
      lupin, pea or a mixture of pea and lupin proteins or in white wines clarified
      with pea proteins. A small number of musts treated with lupin or pea proteins and
      white wines treated with lupin proteins yielded equivocal results, probably
      because of the presence of interfering material (e.g., sugar-rich proteins from
      grape and yeast). The use of bentonite as a secondary clarifying agent is
      therefore recommended since its combination with vegetable proteins is
      particularly effective in removing overall protein immunoreactivity.

PMID- 15244322
TI  - Photolysis of naphthenic acids in natural surface water.
AB  - Naphthenic acids are toxic and corrosive substances in oil sands leachates
      comprising a group of saturated aliphatic and alicyclic carboxylic acids in
      hydrocarbon deposits (petroleum, oil sands bitumen, and crude oils). In the
      current study, photolysis was applied to naphthenic acid mixtures and individual
      compounds to determine the efficacy of a variety of UV/vis radiation sources for
      reducing both concentration and aryl hydrocarbon (Ah) receptor binding as a
      measure of toxicity. The results show that the concentrations of neither the
      compounds nor the mixtures were significantly reduced in Athabasca River water,
      although compositional changes occurred within the mixtures and Ah receptor
      binding potential was affected by photolysis. Photolysis at UV254 was the most
      effective radiation source applied in all instances.

PMID- 15244323
TI  - Photo-assisted oxidation of chlorophenols in aqueous solutions using hydrogen
      peroxide and titanium dioxide.
AB  - In the present work, the efficiency of phenol and chlorophenol degradation under
      irradiation using hydrogen peroxide as oxidant and titanium dioxide powder as
      photo-catalyst was investigated. In the absence of titanium oxide, increased
      concentrations of hydrogen peroxide resulted in higher conversions. Generally,
      phenol was the most readily oxidized compound, whereas in excess of hydrogen
      peroxide, the more chlorine atoms were present in the ring, the less degradable
      the chlorophenol was, in terms of initial rate of oxidation. In the case of 4
      chlorophenol, the catalytic photo-oxidation efficiency with hydrogen peroxide and
      titanium oxide was dependent on the catalyst concentration exhibiting a maximum
      at 0.025-0.05 g L(-1) titanium oxide. The combined use of titanium oxide and
      hydrogen peroxide resulted in higher degree of oxidation compared to results
      obtained when using hydrogen peroxide. Finally, the presence of Fe(III) proved to
      be beneficial for the photo-catalytic oxidation only in the presence of hydrogen
      peroxide.

PMID- 15244324
TI  - Reductive dechlorination of tetrachloroethene by a mixed bacterial culture
      growing on ethyl lactate.
AB  - Chloroethenes like tetrachloroethene (PCE) are the most prevalent groundwater
      contaminants in the USA. Their presence as nonaqueous phase liquids (NAPLs) makes
      remediation difficult. Among options for NAPL cleanup, co-solvent injection has
      demonstrated success. However, the process has the potential to leave
      considerable residue of the co-solvent as well as residual chloroethene. Our
      rationale in this study was to examine whether this residual solvent could be a
      potential electron donor for the remediation of the residual chloroethene. We
      hypothesized that ethyl lactate, a "green" solvent, could serve both as a NAPL
      extraction solvent and an electron donor for reductive dechlorination of residual
      chloroethene. We examined whether a mixed culture known to degrade PCE with
      lactate could also grow on ethyl lactate and whether it could stimulate PCE
      dechlorination. Biomass growth and PCE dechlorination were observed by protein
      and chloride production, respectively, in the culture; with a specific
      dechlorination rate of 50 150 microg (mg cell d)(-1). Ethyl lactate abiotically
      breaks down to ethanol and lactate, the latter being a rich source of hydrogen fo
      reductive dechlorination. The results demonstrate that ethyl lactate may be
      promising for in situ bioremediation following NAPL extraction.

PMID- 15244325
TI  - Microbial indicators for differentiation of human- and pig-sourced fecal
      pollution.
AB  - Microbial indicators, the ratio of fecal coliforms (FC) to fecal streptococci
      (FS) and a newly defined enterococcus ratio, were used to differentiate pollution
      sources. FC FS values for municipal sewage were significantly higher than those
      values of the effluent from piggery wastewater. Enterococcus ratio, the ratio of
      (Enterococcus durans + E. hirae) to (Enterococcus faecalis + E. faecium), of
      human-sourced wastewater (0.90) was much lower than for pig-sourced wastewater
      (5.55). When FC/FS and enterococcus ratio were applied to a contaminated river
      study, both were corresponded well with the population density distribution of
      humans and pigs. FC/FS and enterococcus ratio are feasible microbial indicators
      for human- and pig-sourced wastewater pollution identification in field study.

PMID- 15244326
TI  - Stability of bacterial coaggregates in extreme environments.
AB  - The stability of coaggregates formed by the interaction of Acinetobacter
      johnsonii S35 and Oligotropha carboxidovorans S23, both of which are
      nonflocculating sludge bacteria, was evaluated by a spectrophotometric assay of
      aggregation index and phase contrast microscopy. Exposure of coaggregates to
      conditions of various pH (3-11) or temperature (10-5 degrees C) did not cause
      significant deflocculation and high aggregation index (85-93%) was still
      maintained as compared to 93.3% under normal conditions. Further, heat
      pretreatment of A. johnsonii S35 and O. carboxidovorans S23 cells at 60 or 80
      degrees C did not prevent their subsequent coaggregation indicating that the
      interacting cell surface structures are heat-resistant. However, dual exposure of
      coaggregates to low temperature (10 degrees C) and extreme pH caused disruption
      of coaggregates coupled with the reduction in aggregation index below 28% (pH 3)
      and 49% (pH 11). Use of sterile filtrate of settled sewage (SFSS) in place of
      electrolyte solution as coaggregating medium produced usual large coaggregates
      (above 100 microm) indicating reproducibility of this coaggregation in sewage
      treatment plants. SFSS coaggregates incurred lesser deflocculation (50 and 85%,
      respectively) at extreme pH (3 and 11, respectively) and low temperature. This
      study demonstrated that although bacterial coaggregates are strong and stable
      against individual pH or temperature stress, a dual stress might deteriorate the
      performance and quality of treated waters.

PMID- 15244327
TI  - Cyanobacterial bloom control by ultrasonic irradiation at 20 kHz and 1.7 MHz.
AB  - Ultrasonic irradiations at high frequency of 1.7 MHz and low frequency of 20 kHz
      were tested to prevent cyanobacteria Spirulina platensis from bloom. The
      inhibition effectiveness at 1.7 MHz was much greater than that at 20 kHz. The
      cyanobacteria biomass was reduced by 63% after 5 min ultrasonic irradiation at
      1.7 MHz, whereas three days were needed for the tested cyanobacteria to recover
      its original density. However, longer exposure time did not significantly enhance
      the inhibition. It was observed after ultrasonic irradiation that the gas
      vesicles in cells collapsed, which may result in cyanobacterial precipitation and
      photosynthetic inhibition. The concentration of chlorophyll a (Chla) was reduced
      and its biosynthesis was delayed in a 4-day continuous culture. The fluorescence
      spectra at 77K of phycobilisome (PBS) and absorption spectra of intact cells in
      vivo showed that light energy transfer in PBS was inhibited and phycocyanin (PC)
      was damaged much more acutely compared with Chla. These results indicated that 5
      min ultrasonic irradiation at 1.7 MHz every third day might be an effective and
      economic operation mode for practical application.

PMID- 15244328
TI  - Design of biological filter for iron and manganese removal from water.
AB  - The technology core of biological removal of iron and manganese by contact
      oxidation is iron and manganese oxidizing bacteria. This article made a study on
      down flow and up flow filtration, the results show that down flow filtration of
      the homogenous filter medium is more adapted to the reproduction of biotic
      formation. Homogeneous filter increase the depth of effective biological filter
      and the biomass that develop the bio-chemical capability of the biological
      filter. Homogeneous filter increase removal capability of Fe/Mn and alleviate the
      formation of sludge cake, which can get a quite backwash. Down flow homogeneous
      biological filter can solve some engineering problems of heterogeneous up flow
      filtration. The down flow homogeneous biological filter is more adapted to the
      removal of Fe/Mn in groundwater.

PMID- 15244329
TI  - Eutrophication modeling in Shihmen Reservoir, Taiwan.
AB  - Based on the measured data, including total phosphorus, chlorophyll a, and Secchi
      disk depth, the Shihmen Reservoir in the state of mesotrophic to eutrophic. A two
      dimensional, laterally averaged, finite-difference hydrodynamic, and water
      quality model was applied to simulate water quality conditions in the reservoir
      to determine appropriate strategies for the management of water quality. Data
      collected in the field for a two-year period were utilized to calibrate and
      verify the model. The model calibration and verification were achieved with water
      surface elevation, temperature, and water quality constituents such as nutrients,
      dissolved oxygen, and chlorophyll a. Then the model was used to simulate
      chlorophyll a concentrations under several scenarios corresponding to various
      waste load reduction ratios. A 90% reduction of nutrient loadings will upgrade
      the existing eutrophic/mesotrophic conditions to oligotrophic condition in both
      2001 and 2002, exception January in 2001. The modeling effort had yielded
      valuable information that can be used by decision maker for the evaluation of
      different management strategies of reduction of nutrients coming from the
      catchment area.

PMID- 15244330
TI  - Extraction of heavy metals by 2-mercaptoethoxy groups attached to silica gel.
AB  - Silica gel is currently being used as a support for various straight chain mono-
      and bifunctional compounds such as amines, thiols (mercaptans), and
      mercaptoalochols. The current study reports the results of an investigation of a
      2-mercaptoethoxy moiety covalently attached to silica gel. The condensation was
      effected by acid-catalyzed condensation of toluene solution of 2-mercaptoethanol
      and silica gel and azeotropically removing the water using a Dean-Stark tube. As
      a coordinating agent, this bifunctional compound was used in the removal of
      copper(II), cadmium(II), and lead(II) from standard aqueous solutions. Using
      silica gel support, the removal percentages were 91-93% for the three metals.

PMID- 15244331
TI  - Elemental analysis of soft plaque and calcified plaque deposits from human
      coronary arteries and aorta.
AB  - Twenty-five samples of soft plaque and calcified plaque deposits from human
      hearts or aorta were analyzed using inductively coupled plasma-mass spectrometry
      (ICP-MS). The determined elements were Ca, P, Na, K, Mg, Zn, Cu, Ba, Pb, Fe, Al,
      Si, and S. Results showed that the concentration of all elements in the soft
      plaque was at the micromolar level. In the calcified deposits, the concentrations
      of Ca and P were at least an order of magnitude higher than the soft plaque, but
      the other elements were at the same order of magnitude. In the calcified plaque
      the molar ratios of Ca/P suggested that a significant portion existed as
      hydroxyapatite Ca10(PO4)6(OH)3. However, their absolute concentrations indicated
      that this compound was not a major component of the plaque although it may play a
      major role in determining the crystal structure of the deposit. In some samples
      the Ca/P ratio was too high to conform to hydroxyapatite. In others it was too
      low. This indicated that both the calcium and phosphorus existed in other
      chemical forms which varied from sample to sample. In the soft tissue the P level
      was high indicating it existed primarily in chemical forms other than
      hydroxyapatite. The presence of homocysteine is often associated with heart
      disease. However, the low levels of sulfur indicate that although it may be
      present, it is not a major component of the plaque, but may nevertheless play an
      important role in its formation.

PMID- 15244332
TI  - Determination of elements in native and bypass human coronary artery plaque
      deposits from the same heart using inductively coupled plasma-mass spectrometry.
AB  - As part of an ongoing study on atherosclerotic arteries, the concentrations of 12
      elements in a native and by-pass human coronary artery plaque deposits from five
      human hearts were determined using inductively coupled plasma-mass spectrometry
      (ICP-MS). These elements were Ca, P, Na, K, Mg, Zn, Cu, Pb, Fe, Al, Si, and S.
      For Zn, Ca, Pb, Fe, Al, and Si, the levels were at the fractional micromol/g
      levels and they probably played an unimportant role in plaque development. Sulfur
      levels varied from 23 to 140 micromols indicative of the possible presence of
      homocysteine, but there appeared to be no consistent relationship between by-pass
      and native concentrations. The calcium and phosphorus concentrations were
      relatively high in all cases, but the ratio of their molecular concentrations did
      not correspond to hydroxyapatite, which is conventionally considered to be the
      chemical form of calcium in heart plaque. In the mature native plaque, high
      calcium/phosphorus ratios indicated calcium in chemical forms other than
      hydroxyapatite. In undeveloped by-pass plaque, the phosphorus concentration was
      too high to be as hydroxyapatite but may be phospholipids. Because it is
      difficult to get suitable samples, only five heart samples were available.
      Therefore, these results should be treated as preliminary.

PMID- 15244334
TI  - Using genetic algorithm to identify completely unknown system in FTIR spectra
      analysis.
AB  - The article mainly focuses on how to identify completely unknown systems in FTIR
      spectra analysis by Genetic Algorithm (GA). The technique of multiplespot
      crossover combined with quantitative and adaptive mutation is used and the whole
      process is controlled by the fitness value and probability of selection in GA. A
      standard pure FTIR spectra database containing 101 air toxic organic compounds is
      set up. Six unknown samples are identified and quantitatively analyzed. The
      results indicate that GA can successfully identify even a perplexing sample
      containing 18 components. The concentration of each component in the samples can
      be determined at the same time. The maximal relative error is no more than 10%.
      It means that GA has the capability of simultaneous identification and
      prediction, especially for those completely unknown mixed spectra in FTIR.

PMID- 15244333
TI  - Computational prediction of 7-ethoxyresorufin-O-diethylase (EROD) and luciferase
      (luc) inducing potency for 75 congeners of chloronaphthalene.
AB  - Based on available toxicological data and matrix of structural descriptors 7
      ethoxyresorufin-O-diethylase (EROD) and luciferase (luc) inducing potency for 75
      congeners of chloronaphthalene was predicted using quantitative structure
      activity relationships (QSAR) strategy. The most active congeners in EROD and
      luciferase bioassays were CN congeners nos. 75 and 67. Some empirical rules
      describing toxic PCNs were formulated.

PMID- 15244335
TI  - Identification of recalcitrant hydrocarbons present in a drilling waste-polluted
      soil.
AB  - During spills of hydrocarbons in soil, it has been observed that aliphatic and
      the slightly aromatic hydrocarbons are first to be removed, however, branched
      aliphatic and aromatic compounds, polycyclic aromatic hydrocarbons (PAHs) and
      their similar heteroatoms with sulfur (PAS) remain strongly absorbed to soil
      particles. It is important to point out that studies of biodegradation of alkyl
      substituted PAHs and PAS are scarce and most of them have been carried out using
      only available standard compounds. The aim of this investigation was to identify
      and to quantify the aliphatic, alkyl polycyclic aromatic, and sulfured
      recalcitrant fractions present in a contaminated soil with drilling wastes. A
      modified method of shaking-centrifugation extraction was implemented for the
      extraction of compounds from contaminated soil. The organic extract obtained was
      purified and fractionated using aluminum oxide. Gas Chromatograph with flame
      ionization detector (GC-FID) and Gas Chromatograph with mass spectrometer
      detector (GC-MS) identified the aliphatic, PAHs and PAS fractions. Hydrocarbon
      composition in the soil contaminated with 140,000 mg TPHs/Kg soil, consisted in
      80% of branched aliphatic compounds of C10 to C22, 15% of alkyl PAHs, and 5% of
      PAS compounds. Lineal, lineal branched, and cyclic branched aliphatic
      hydrocarbons, as well as their alkyl naphthalene, anthracene and phenantrene,
      methyldibenzothiophene, dimethyldibenzothiophene, and dimethylnaphto[2,3
      b]thiophene compounds were identified by CG-MS. The identification of compounds
      in soil P31, allowed us to speculate on the origin of the contamination and the
      natural attenuation that had occurred at this site.

PMID- 15244336
TI  - Trace metal distribution in surface soils of Novi Sad and bank sediment of the
      Danube River.
AB  - Concentration ofCu. Cd, Pb, Zn, As, Mn, and Fe in the Novi Sad city urban area
      surface soil samples and the Danube bank sediment sample were measured in 2001.
      The results correspond to a network of six representative sampling sites in which
      the main soil properties, organic matter, water content, pH, and particle size
      have also been determined. The geometric mean content of Zn, Cu, Cd, and Pb
      obtained from soil samples throughout the Novi Sad urban area (61.32, 28.39,
      0.151, and 2.70 mg/kg, respectively) was compared with the geometric mean
      concentration in world soils. It was revealed only one site (sampling site No. 3)
      with Zn and Cu content higher than the allowed ones set by Dutch authorities used
      for investigation of a site for possible rehabilitation (Dutch A values).

PMID- 15244337
TI  - Use of plants to monitor contamination of air by SO2 in and around refinery.
AB  - The generation of SO2 from a refinery may affect the surrounding environment.
      Moreover, SO2 and its by-products are phytotoxic as berg. This study aims to
      investigate plant responses to SO2. The work has been designed with emphasis on
      using the plants directly in monitoring the contamination of the atmospheric air
      by SO2. An assessment was made of the impacts of long-term SO2 emissions from an
      oil refinery on plants located in nearby areas that are likely to be exposed to
      emission fallout. Three different plant species (Prosopis cineraria. Azadirachta
      indica, and Phoenix dactilifera) common to the environment of the Arabian Gulf
      were selected at different distances and directions from the refinery. The
      analysis of the sulphate contents of these plants were used as bioindicators for
      monitoring SO2 concentration levels in and around the refinery. The results of
      this study showed that the three different plant species responsed differently to
      SO2 in terms of their sulphate contents. Generally, all three species were found
      to be sensitive to SO2 exposure. Furthermore, the concentration of sulphate was
      found to be much higher closer to the refinery. On the basis of this study, it
      can be stated that even though SO2 levels were lower than the permissible limit
      values, the sulphate contents accumulated in the plants were likely to cause
      plant injury especially in the vicinity of the source. This suggests that the
      present environmental guidelines for SO2 may not protect sensitive plant species.

PMID- 15244338
TI  - Evaluation of techniques for control of disinfection by-products: a pilot study.
AB  - The purpose of this study was to evaluate the effects of various treatment
      processes as they relate to the development of disinfection by-products (DBPs).
      At an existing municipal water supply, several tests were performed, including:
      air-stripping, potassium permanganate (KMnO4) addition, pH adjustment, evaluation
      of corrosion control inhibitors, final disinfection, and granular activated
      carbon (CAC) filtration. Several HAAs were shown to increase at higher pH. The
      use of air stripping greatly reduced the required amount of chlorine
      disinfectant. Air stripping, permanganate addition, and chloramination reduced
      DBPs below 20 microg/L. Stiles-Kem 7840 addition effectively controlled lead and
      copper concentrations in the distribution system. The use of chloramination its a
      secondary disinfectant is recommended to meet stage 1 of the disinfection by
      product rule.

PMID- 15244339
TI  - Leaching behavior of lead from ultrasonically treated MSWI fly ash.
AB  - This study was conducted to evaluate the effect of ultrasound widely used for
      extraction of contaminants and for synthesis of complexes, on extraction and
      stabilization of heavy metals in MSWI fly ash. Ten grams of fly ash was treated
      at 10 of liquid--solid (L/S) ratio with and without ultrasonic irradiation of 20
      kHz. The extractability of Pb from fly ash was enhanced by ultrasound at the
      acidic condition. At neutral and alkaline conditions, however, ultrasound did not
      affect the enhancement of extractability. The results of the maximum availability
      leaching test (MALT) of the residues treated under various pH conditions with or
      without ultrasound indicated that the stability of Pb in the fly ash residues was
      enhanced after ultrasonic irradiation irrespective of treated pH conditions.
      However, there was a critical point on the enhancement of lead stability in the
      residues even though the extraction efficiency of Pb decreased gradually with
      increasing ultrasonic intensity during fly ash treatment. Ultrasonic irradiation
      was effective for phosphate stabilization of Pb in fly ash. Irrespective of
      leaching tests, less amount of Pb was leached out from the phosphate stabilized
      residues treated with ultrasound than without ultrasound. The extraction
      efficiency of Pb from fly ash decreased with increasing treatment time but the
      fractions available for leaching at MALT increased with increasing treatment
      time. Conclusively, although the effect of ultrasound on the extraction of Pb
      from fly ash highly depends on the pH condition of solvent, the stability of lead
      in the fly ash residues can be enhanced with ultrasonic irradiation.

PMID- 15244340
TI  - Behavior of toxic metals and radionuclides during molten salt oxidation of
      chlorinated plastics.
AB  - Molten salt oxidation is one of the promising alternatives to incineration for
      chlorinated organics without the emission of chlorinated organic pollutants. This
      study investigated the behavior of three hazardous metals (Cd, Pb, and Cr) and
      four radioactive metal surrogates (Cs, Ce, Gd, and Sm) in the molten Na2CO3
      oxidation reactor during the destruction of PVC plastics. In the tested
      temperature ranges (1143 1223K) and NaCl content (0-10%), the impact of
      temperature on the retention of cadmium and lead in the molten salt reactor was
      very small, but that of the NaCl content for their retention was relatively
      higher. The influence of NaCl accumulation was, however, proven to be practically
      negligible due to the low-temperature operating characteristics of the molten
      salt oxidation system. Neither temperature increase nor chlorine accumulation in
      the MSO reactor reduced the retention of Cr, Ce, Gd, and Sm. Over 99.98% of these
      metals remained in the reactor. The influence of the temperature on the cesium
      behavior is relatively large for a chlorine addition, however, over 99.7% of
      cesium remained in the reactor throughout the entire test. The experimental metal
      entrainment rate and the entrained metal particle size distribution agree well
      with the theoretical equilibrium metal distributions.

PMID- 15244341
TI  - Retardation of phosphate release from freshwater benthic sediments by application
      of ocher pellets with calcium nitrate.
AB  - This article presents an in situ treatment method for retardation of phosphate
      release from freshwater benthic sediments. The method is based on the addition of
      ocher pellets into benthic sediments. The pellets consist of ocher and calcium
      nitrate (OCN pellet). The OCN pellet slowly releases calcium and nitrate,
      together with ocher, into the sediment water interface, where all three
      components play an important role in reducing phosphate release from sediments.
      Each component was applied to sediments to examine the individual effects in this
      study. Bench scale experiments were performed with the following treatments: (1)
      ocher, (2) calcium, (3) nitrate, (4) calcium nitrate, (5) calcium nitrate and
      ocher, and 6) no treatment. The sediment without any treatment released a
      phosphate flux of 10.82 mg/m2/d. The sediment with ocher, calcium, and nitrate
      treatments, released phosphate fluxes of 8.41, 6.41, and 0.95 mg/m2/d,
      respectively. This can be attributed to the fact that nitrate, acting as an
      electron acceptor of organic matter degradation, prevents the dissolution of
      phosphate bound to iron oxides. In addition, calcium and ocher can bind the
      dissolved phosphate. An increase of pH together with nitrate reduction helps the
      calcium bind to phosphate. Ocher also can act as a vehicle to bring the calcium
      nitrate from the water surface to the bottom. The proposed method has two major
      advantages compared to previous methods: (1) effective reduction of phosphate
      release due to the synergism of calcium, nitrate, and ocher; and (2) ease of use
      in natural systems, in such manner that the OCN pellets can be simply scattered
      over the water surface.

PMID- 15244342
TI  - Study on catalytic incineration of methane using Cr2O3/gamma-Al2O3 as the
      catalyst.
AB  - A fixed bed reactor was employed to investigate the catalytic incineration of CH4
      by various supported transition metal oxide catalysts, with a view of finding the
      optimal one. Results indicated that the active species, the support, the metal
      content, the weight hourly space velocity (WHSV), and the inlet CH4 concentration
      were all important factors affecting CH4 oxidation. Cr2O3/gamma-Al2O3 was found
      to be the most active catalyst among the seven gamma-Al2O3-supported metal oxide
      catalysts tested. With Cr2O3 as the active species, gamma-Al2O3 was the most
      suitable of six supports tested. Furthermore, the optimal Cr content of Cr2O3/
      gamma-Al2O3 was 9 wt.%. X-ray diffraction (XRD) patterns showed that it was
      formation of CrO3 crystals that caused a decline in catalyst activity at Cr
      content above 9wt.%. Using the optimal Cr2O3/gamma-Al2O3 catalyst, CH4 was
      completely oxidized at about 390 degrees C. much lower than the temperature
      required by noble metal catalysts for the same outcome. The stability of
      Cr2O3/gamma-Al2O3 was good and was not affected by the reaction temperature,
      demonstrated by a nearly constant conversion rate of CH4 of 57% at 350 degrees C
      and 97% at 380 degrees C during a 20 h on-stream test. However, WHSV and inlet
      concentration of CH4 did affect CH4 conversion noticeably. For complete oxidation
      of CH4, the reaction temperature required increased with WHSV and inlet CH4
      concentration.

PMID- 15244343
TI  - Non-synaptic interaction between neurons in the brain, an analog system: far from
      Cajal-Sherringtons's galaxy.
AB  - The functional interactions between neurons without synaptic contacts are
      specialized to function on a time scale of seconds (minutes) and a distance scale
      of hundreds of micrometers. These nonsynaptic receptors and transporters are of
      high affinity, have many implications for psychiatry for understanding e.g.
      depression, changes in mood, in appetite, affective illnesses etc. It is,
      therefore, suggested that many drugs applied in psychiatric diseases, exert their
      effects after diffusion through extracellular spaces and may mimic the mode, or
      may influence the effect of endogenous ligands. The nonsynaptic chemical
      communication between neurons, and between neurones and target cells, via both
      pre- and postsynaptic sites, seems likely to achieve growing recognition. This
      system has a similar degree of selectivity to that of synaptic circuitry but
      have, in addition, a domain of versatility and plasticity in "hardwired"
      circuitry. The brain is a wired instrument, but its neurons, besides cabled
      information processing (through synapses), are able to talk to each other without
      synaptic contact. It is suggested, therefore that the nonsynaptic tonic
      presynaptic modulation of chemical transmission, plays a physiological role in
      the brain in shaping emotion, behaviour or learning processes, or in controlling
      the balance between sympathetic and parasympathetic nervous system, or the
      nonsynaptic released transmitter is able to produce responses of the target cells
      and a local fine tuning of cytokine production (cf. Elenkov et al., 2000),
      steroid secretion and possible many other functions not yet discovered. The
      spatial and temporal effect of transmitters on nonsynaptic receptors located on
      axon terminals, adopts the strength of transmission to a given situation. This
      will not only influence the function of the neurons system in health and disease,
      but also therapeutic and untoward effects of drugs that bind these nonsynaptic
      receptors and transporters (Vizi, 2000).

PMID- 15244344
TI  - [Role of endo-osseus implant in odonto-oral rehabilitation].
AB  - Dental implants have critically changed the restorative procedures available to
      edentulous patients. Biocompatible materials, precise surgical techniques and
      improved instrumentation give well trained practicioners various opportunities to
      achieve successful treatments. The necessity of combining full expertise in
      surgery and rational prosthetic planning with comprehensive occlusal management
      is emphasized. Recent advances in periodontal treatment of osseous and soft
      tissue defects, new grafting techniques and surgical approaches have dramatically
      enlarged the scope of oral implantology.

PMID- 15244346
TI  - [The beautiful adventure of Televie].

PMID- 15244345
TI  - [Contribution of F.N.R.S. and of its associated Fonds to the development of
      medical scientific research in the French Community of Belgium].
AB  - Basic life sciences hold a preponderant position amongst scientific research
      supported by the FNRS and its associated funds in the French Community of
      Belgium. This status shows itself in training for researchers as well as in the
      development of research program, and even in the scientific influence of
      researchers in Belgium and abroad. An associated fund, the F.R.S.M., and
      "Televie" are devoted to them. However, the financial means of the French
      Community of Belgium remain limited and are considerably lower than those of our
      neighbouring countries. So what is the future for medical scientific research in
      our Community?

PMID- 15244347
TI  - [Cell therapy for heart failure].

PMID- 15244348
TI  - On professionalism.

PMID- 15244349
TI  - Acute medicine: making it work for patients.

PMID- 15244350
TI  - Pleural effusions.

PMID- 15244351
TI  - Pulmonary hypertension: diagnosis and treatment.

PMID- 15244352
TI  - Suspected pulmonary embolism.

PMID- 15244353
TI  - Outpatient management of chronic obstructive pulmonary disease.

PMID- 15244354
TI  - Community acquired pneumonia.

PMID- 15244355
TI  - Developing clinical ethics committees.
AB  - Formal clinical ethics review first developed in the USA and most hospitals there
      have structures in place. This is often a clinical ethics committee. Developments
      have been slower in the UK, where there has been uncertainty and variability
      about the role of clinical ethics committees. Even in the USA, their exact role
      is uncertain. Although we now have a good idea of the mechanisms for ethical
      review of clinical issues in NHS trusts and health authorities, the desirability,
      composition and terms of reference for clinical ethics committees should be
      agreed as part of the clinical governance agenda.

PMID- 15244356
TI  - Percutaneous endoscopic gastrostomy: an effective strategy for gastrostomy
      feeding in patients with dementia.
AB  - Percutaneous endoscopic gastrostomy (PEG) is an accepted technique for longterm
      enteral feeding. Its use has increased because of its simplicity and low
      complication rate. The demands for gastrostomy insertion have risen and now
      encompass indications where the long-term outcomes are uncertain. Dementia has
      become one of the commonest indications for gastrostomy feeding. This article
      reviews the justification for PEG feeding in dementia and suggests a practical
      approach for this difficult clinical situation. The clinical strategy described
      in this paper can be applied to other neurodegenerative diseases and provides a
      framework for improving a PEG service.

PMID- 15244357
TI  - 'If it helps my patient...' Perspectives on complementary medicine.
AB  - The argument 'if it helps my patient, I don't need science to prove that it
      works' is rife in complementary medicine. This article is an attempt to examine
      it from the perspective of the provider of complementary medicine, the clinical
      scientist and the politician. It is concluded that the dichotomy between
      experience and science is a regrettable misunderstanding. The revised argument
      should be 'if it helps my patient, I want research undertaken to find out whether
      more people could benefit from it'.

PMID- 15244358
TI  - The good doctor: the carer's perspective.
AB  - Carers are family members, friends, and neighbours who perform medical tasks and
      personal care, manage housekeeping and financial affairs, and provide emotional
      support to people who are ill, disabled, or elderly. From a carer's perspective,
      the primary requisite for a good doctor is competence. Assuming equal technical
      skills and knowledge, the difference between 'good' and 'bad' doctors comes down
      to attitudes and behaviour-communication. An important aspect of communication is
      what doctors say to carers, and how they interpret what carers say to them. Body
      language-stances, gestures and expression-communicates as well. Good doctors are
      surrounded by courteous, helpful and efficient assistants. Doctors can make two
      types of errors in dealing with carers. Type 1 errors occur when doctors exclude
      the carer from decision making and information. Type 2 errors occur when doctors
      speak only to the carer and ignore the patient. Good doctors, patients and carers
      confront the existential meaning of illness together.

PMID- 15244359
TI  - Protecting and using patient information: the role of the Caldicott Guardian.
AB  - All patient information is confidential and must be protected and used
      appropriately by all members of the healthcare team. Caldicott Guardians have a
      strategic, advisory and facilitative role to ensure that the Caldicott Principles
      underpin the approach organizations develop to protect and use patient
      identifiable information. It is essential all staff and students receive
      appropriate training and are aware that the responsibility for protecting and
      using patient information lies with the organisation headed by the Chief
      Executive and with each individual.

PMID- 15244360
TI  - The eye in systemic vasculitis.
AB  - The term 'vasculitis' includes a wide range of disorders characterised by
      inflammation of the wall of blood vessels, sometimes with necrosis, leading to
      ischaemia of the affected organ. The exact pathogenesis of most of these
      vasculitides is not fully understood and although the presence of circulating
      auto-antibodies seems to be a common feature among them, each vasculitis has its
      unique pathogenesis and a predilection for vessels of a defined size. Systemic
      vasculitis may be associated with ocular complications which include scleritis,
      keratitis, uveitis and optic neuropathy. These can precede the symptoms/signs of
      the systemic disease and therefore their recognition may lead to detection of the
      underlying disorder. The eye may also be affected by the treatment required to
      control the systemic disease.

PMID- 15244361
TI  - The need for mandatory clinical recording standards.
AB  - Current health information initiatives and targets set by the UK government have
      brought about a flurry of activity in the National Health Service to try to reach
      those targets. One target is to implement an electronic patient record system as
      a replacement for the present paper-based system of record keeping. However, this
      will not be an easy task; simply introducing information technology into an
      already chaotic system will only compound existing problems. This article
      highlights the gaps that must be filled before an electronic record system can be
      effectively implemented. The two major elements that are missing are mandatory
      clinical recording standards and a profession that is responsible for monitoring
      and enforcing those standards. Some examples of relevant standards for clinical
      recording are provided and the role of a health information management profession
      is described.

PMID- 15244362
TI  - The story of Clostridium botulinum: from food poisoning to Botox.
AB  - In the last fifty years, Clostridium botulinum has become notorious for its
      ability to produce the deadly botulinum neurotoxins. While botulinum toxin A,
      better known as Botox, is universally recognised by the public as a cosmetic
      enhancement tool, the botulinum neurotoxins are commonly used off-label for many
      medical conditions in ophthalmology, neurology and dermatology. The versatility
      of these botulinum toxins has made Clostridium botulinum one of the most widely
      known bacterial pathogens in medical history. This article outlines the discovery
      of botulinum toxins through to their present day applications in medicine.

PMID- 15244363
TI  - Intensive care requirements for an ageing population--a microcosm of problems
      facing the NHS?
AB  - The changing patterns of admissions to an intensive care unit (ICU) were
      investigated in relation to age. The local population and the patients admitted
      to ICU in each year from 1996 to 2002 were stratified by age. The trend in the
      ratio of admissions to population showed the most extreme changes in those aged >
      or = 60 years. For this group, there was an increase of 2.62 admissions per
      10,000 population per year (95% Confidence interval (CI) 1.41 to 3.85, p =
      0.004). APACHE II (Acute Physiology and Chronic Health Evaluation II) scores
      increased by 0.45 points per year (95% CI 0.16 to 0.74, p = 0.013) and length of
      ICU stay increased by 0.21 days per year (95% CI 0.03 to 0.38, p = 0.032). This
      rapid increase in the use of ICU resources by patients aged > or = 60 years over
      a period of six years, combined with an ageing population, suggests that current
      projections of future ICU provision may be inadequate.

PMID- 15244364
TI  - Accountability, trust and informed consent in medical practice and research.
AB  - During the last 25 years public policy in the UK has aimed to replace 'club'
      cultures and their supposedly suspect reliance on trust between professionals and
      public with a new public culture based on accountability and 'transparency'.
      These transformations have changed both clinical practice and public health
      policy in deep ways. Are the new conceptions of accountability adequate? Are
      obligations to be 'transparent' any more than requirements to disclose
      information which overlook the need for genuine communication? Can demands for
      ever fuller informed consent improve accountability to individual patients and
      research subjects? Could we devise more intelligent conceptions of accountability
      that support more intelligent placing and refusal of trust? What might
      intelligent conceptions of accountability suggest about proper clinical practice,
      public health medicine and professional responsibilities?

PMID- 15244365
TI  - Recent advances in diabetic nephropathy.
AB  - Diabetic nephropathy is the most common cause world-wide of renal failure
      requiring renal replacement therapy, most patients having type 2 rather than type
      1 diabetes. Cardiovascular risk increases progressively as nephropathy develops.
      In addition to abnormalities in the glomerular endothelium and mesangium, recent
      data suggest that changes are also seen in the glomerular epithelial cell or
      podocyte. The foot processes of the podocyte broaden and efface and there is loss
      of podocyte specific proteins such as nephrin. Eventually there is loss of
      podocytes themselves. These changes may contribute to proteinuria. The
      development of nephropathy can be prevented by good glucose and blood pressure
      control. Once microalbuminuria or proteinuria are present, control of
      intraglomerular pressure, using inhibitors of the renin-angiotensin system, and
      control of systemic blood pressure are paramount, and can delay the need for
      renal replacement therapy by many years. Aggressive management of cardiovascular
      risk factors also slows the progression of nephropathy and prevents
      cardiovascular events.

PMID- 15244366
TI  - I waxes and I wanes, Sir.

PMID- 15244367
TI  - Careers in academic medicine.

PMID- 15244368
TI  - Withdrawing nutrition and hydration.

PMID- 15244369
TI  - Diagnosing acute headache.

PMID- 15244370
TI  - Bioterrorism: the need to be prepared.

PMID- 15244371
TI  - Liaison neurology for acute medical admissions.

PMID- 15244372
TI  - Morphological features of the microdistribution of naturally occurring 10Pb/2l0Po
      and 226Ra in the teeth of children and juveniles.
AB  - PURPOSE: To examine the microdistribution of natural alpha-radioactivity in
      deciduous teeth of children and the permanent teeth of juveniles extracted for
      orthodontic purpose from across the UK. MATERIALS AND METHODS: The
      microdistribution of 210Pb-supported 210Po and 226Ra in 708 deciduous and
      permanent teeth and 32 foetal teeth was measured on 1442 TASTRAK alpha-particle
      track detectors. RESULTS: Of the various findings, a number are of special
      interest. Around half of the 210Pb activity in the outer enamel of deciduous
      teeth appears to have been acquired in utero as a result of transplacental
      transfer. In deciduous and permanent teeth, 226Ra is concentrated mainly in the
      circumpulpal region, while the highest levels of 210Po are on the highly
      calcified outer enamel surface. Furthermore, activity concentrations recorded on
      this surface were In-normally distributed. CONCLUSIONS: 210Pb-supported 210Po
      activity on the outer enamel surface of permanent teeth constitutes an assay of
      cumulative environmental exposure with which to assess exposure in bone, both in
      utero and in childhood. Such assessment can be used to study geographical
      variations in the alpha-activity in teeth. More work is also required to
      determine the concentrations of both 210Po and 210Pb in the foetal skeleton.

PMID- 15244373
TI  - Aspects of the geographical variations of naturally occurring 210Pb/210Po in
      permanent teeth of juveniles in the UK.
AB  - PURPOSE: To study geographical variations in the level of naturally occurring
      210Pb-supported 210Po in permanent teeth of juveniles in the UK. MATERIALS AND
      METHODS: Permanent teeth extracted from 278 juveniles for orthodontic purposes
      were obtained from 48 counties in the UK. 210Po activity concentration was
      measured on the outer enamel surface using TASTRAK alpha-particle-sensitive
      plastic track detectors. RESULTS: Geometric mean +/- SE activity concentrations
      in teeth from urban, suburban and rural areas, excluding the high radon area of
      Devon, were 8.41 + 0.25/-0.24, 7.76 + 0.37/-0.35 and 7.20 +0.49/-0.46 Bq kg(-1),
      respectively. Overall, there was no significant association between alpha
      activity on the outer enamel surface of permanent teeth and proximity to the
      major UK motorways. However, when the data were considered with respect to the
      prevailing south-westerly wind on the western side of the UK, a statistically
      significant association with respect to donors living downwind (on the easterly
      side) of the motorways was found. This effect was greater for sections of the M5
      and M6 motorways that traverse urban areas. 210Po levels in teeth were also
      associated with domestic radon concentration. This effect was comparable with
      that from traffic and urban pollution. CONCLUSIONS: Higher levels of 210Pb
      supported 210Po are seen in permanent teeth of juveniles near sources of
      increased exposure in the UK. Inhalation uptake is an important pathway of
      exposure, especially with respect to domestic radon exposure. The results might
      be important in assessing integrated exposure to 210Po in the skeleton and
      consequent high linear energy transfer dose to bone marrow.

PMID- 15244374
TI  - Oxidative and genotoxic damage after radio-iodine therapy of Graves'
      hyperthyroidism.
AB  - PURPOSE: To evaluate genetic damage and oxidative stress following a single
      therapeutic dose of 131I in Graves' disease patients monitored up to 180 days
      after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as
      the increase in micronuclei in peripheral lymphocytes of patients. As indicators
      of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed
      in the plasma of patients, as well as the release of plasmic clastogenic factors
      measured by the induction of micronuclei in vitro in peripheral lymphocytes of a
      healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal
      level was restored within 7 days. No statistically significant variations were
      observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the
      peripheral lymphocytes of patients was correlated (p < 0.001) with the release of
      clastogenic factor in the plasma. The highest micronucleus value was negatively
      correlated (p < 0.03) with the lowest vitamin E level observed in each patient.
      CONCLUSIONS: Micronuclei induction was the direct consequence not only of the
      energy deposition of 131I on the genetic material, but also of oxidative stress,
      likely via the release of clastogenic factor.

PMID- 15244375
TI  - Novel radioprotectant drugs for sparing radiation-induced damage to the physis.
AB  - PURPOSE: To determine if pentoxifylline, interleukin 1alpha, selenium and
      misoprostol can minimize damage to physeal longitudinal growth during single
      radiation dose exposure in an animal model. MATERIALS AND METHODS: Eighty-seven
      weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups
      received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left
      limb serving as an internal control. Pentoxifylline was injected 30 min before
      exposure, sodium selenite and interleukin 1alpha 24 h before exposure and
      misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks,
      animals were sacrificed, the hind limb lengths were measured and detailed
      histomorphometric analysis was performed. RESULTS: Statistically significant
      reductions (p < or = 0.03) in mean limb length discrepancy compared with
      irradiation alone were seen following administration of pentoxifylline (50 mg kg(
      1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol
      (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6
      weeks despite treatment, but length discrepancy reduction was highly correlated
      with the appearance of regenerative clones. CONCLUSIONS: Each drug reduced the
      amount of anticipated growth arrest in the animal model and some compared
      favourably in magnitude with that previously demonstrated for the established
      radioprotectant drug amifostine. Restoration of growth appears related to
      appearance of regenerative clones.

PMID- 15244376
TI  - DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed
      field gel electrophoresis. II. Simulation with a generalized broken stick model.
AB  - PURPOSE: To characterize the differences among the experimental DNA fragmentation
      spectra induced in Chinese hamster V79 cells by gamma-rays, low-energy protons
      and alpha-particles through the use of a phenomenological model. MATERIALS AND
      METHODS: A model of DNA fragmentation was developed as a generalization of the
      broken-stick model, in which the double-strand breaks induced by radiation were
      considered randomly placed, but in which the manifestly non-random fragmentation
      of the control sample was fully taken into account and considered as the initial
      fragment distribution. Further, an analytical method was introduced that allowed
      an evaluation of the deviation from randomness of the fragmentation induced by
      radiation. RESULTS: The analysis of the experimental distribution of DNA
      fragments showed that there was a progressive departure from randomness in
      radiation-induced fragmentation going from gamma-rays to protons and then to
      alpha-particles. This deviation was characterized by an enhanced induction of
      fragments, and therefore by a larger correlation of double-strand breaks, in the
      experimental range of lower molecular weights. CONCLUSION: The analysis shows
      that low-energy light ions induce DNA fragmentation, at the loop level of the
      chromatin organization, that can be significantly non-random. The same analysis
      can readily be applied at different length scales, and thus it could offer a
      basis for the study of the link between DNA damage, correlated at various spatial
      scales and biological end-points.

PMID- 15244377
TI  - Radiation-induced fragmentation of cardiolipin in a model membrane.
AB  - PURPOSE: To obtain evidence for the possibility of free-radical fragmentation of
      cardiolipin under the action of ionizing radiation as measured by its aqueous
      dispersion from liposomes. MATERIALS AND METHODS: Liposomes of
      tetramyristoylcardiolipin (TMCL) were exposed to gamma-rays from 60Co or 137Cs
      sources at doses between 1 and 24kGy. Fragmentation products were identified
      using thin-layer chromatography and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Using MALDI-TOF MS and
      thin-layer chromatography, it was shown that gamma-irradiation of liposomes
      consisting of TMCL was accompanied by free-radical fragmentation of the lipid to
      form dimiristoylphosphatidic acid and dimiristoylphosphatidyl hydroxyacetone. The
      yields of dimiristoylphosphatidic acid were greater than those of
      dimiristoylphosphatidyl hydroxyacetone, and formation of the named compounds was
      inhibited by dissolved oxygen. CONCLUSION: It is shown for the first time that on
      gamma-irradiation, cardiolipin can undergo free-radical fragmentation in its
      polar component.

PMID- 15244378
TI  - John Rock: pioneer in the development of oral contraceptives.

PMID- 15244379
TI  - On the "significance" of monoclonal gammopathy of undetermined significance.

PMID- 15244380
TI  - Myelofibrosis: thalidomide finds a new disease.

PMID- 15244381
TI  - Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined
      significance: the original Mayo Clinic series 25 years later.
AB  - OBJECTIVE: To determine the long-term outcome of patients with monoclonal
      gammopathy of undetermined significance (MGUS). PATIENTS AND METHODS: We reviewed
      the medical records of 241 patients with MGUS who were examined at the Mayo
      Clinic in Rochester, Minn, between January 1, 1956, and December 31, 1970.
      RESULTS: Follow-up was 3579 person-years (median, 13.7 years; range, 0-39 years).
      Only 14 patients (6%) were alive and had no substantial increase of M protein at
      last follow-up; 138 patients (57%) died without evidence of multiple myeloma or a
      related disorder; a malignant lymphoplasma cell proliferative disorder developed
      in 64 patients (27%). The interval from diagnosis of MGUS to diagnosis of
      multiple myeloma or related disorder ranged from 1 to 32 years (median, 10.4
      years). CONCLUSIONS: The median survival rate of study patients with MGUS was
      only slightly shorter than that of a comparable US population. Risk of
      progression of MGUS to lymphoplasma cell malignancy is indefinite and persists
      even after more than 30 years of follow-up, with no reliable predictors of
      malignant evolution.

PMID- 15244382
TI  - Clinical course of patients with relapsed multiple myeloma.
AB  - OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM)
      that relapses after initial therapy. PATIENTS AND METHODS: Patients with MM, seen
      at the Mayo Clinic in Rochester, Minn, between January 1, 1985, and December 31,
      1998, were identified from a prospectively maintained database. Our study
      population consisted of 578 patients with newly diagnosed MM who were followed up
      and monitored throughout their clinical course at our institution. RESULTS: The
      median age of the 578 patients with MM was 65 years (range, 26-92 years); 228
      patients (39%) were women. The median follow-up of 71 surviving patients was 55
      months (range, 0-202 months). The overall survival (OS) for the 578 patients at
      1, 2, and 5 years was 72%, 55%, and 22%, respectively; the median OS from initial
      therapy was 28.4 months. The median OS of 355 patients who experienced relapse
      after initial treatment was 17.1 months from initiation of the second therapy,
      and 84% died within 5 years. The duration of response decreased consistently with
      each successive regimen. Patients with a high plasma cell labeling index (> or =
      1.0%), low platelet count (< 150 x 10(9)/L), high creatinine level (> or = 2.0
      mg/dL), and low albumin level (< 3.0 g/dL) had a poorer prognosis. CONCLUSIONS:
      Our study revealed decreasing response duration with increasing number of salvage
      regimens, probably reflecting acquired drug resistance and an increasing
      proliferative rate of the myeloma cells. Patients who experienced relapse after
      initial treatment and received salvage therapy had a median survival of nearly
      1.5 years. This must be remembered when making treatment decisions for these
      patients and must be factored in when assessing the efficacy of new therapies.

PMID- 15244385
TI  - Characteristics of 100 consecutive patients presenting with orthostatic
      hypotension.
AB  - OBJECTIVE: To elucidate the demographic and clinical characteristics of a
      consecutive series of patients who presented for evaluation of orthostatic
      hypotension. PATIENTS AND METHODS: From January 1, 1997, through September 30,
      2001, we assessed retrospectively the demographic and clinical characteristics,
      antihypertensive medication use, and blood pressure variability in 100
      consecutive patients with orthostatic hypotension who underwent 24-hour
      ambulatory blood pressure monitoring (OH group) and in a convenience sample of
      100 age-matched patients who underwent 24-hour ambulatory blood pressure
      monitoring for evaluation of hypertension (HTN group). RESULTS: The OH group had
      a mean +/- SD age of 71.6 +/- 9.4 years, and 42% were women. The most common
      symptoms were light-headedness and weakness. Comorbid conditions included
      neurologic diseases (38%), preexisting hypertension (36%), hyperlipidemia (31%),
      cardiac arrhythmias and coronary artery disease (45%), and neoplasm (28%). During
      ambulatory blood pressure monitoring, postprandial decreases in blood pressure
      were noted in 83% of the OH group, supine or sleep hypertension in 84%, and
      noncompensatory heart rate variability in 75%. Findings on autonomic testing were
      abnormal in 99% of patients, serum creatinine value was increased in 30%,
      proteinuria was present in 27%, and left ventricular hypertrophy was present in
      20%. CONCLUSIONS: Orthostatic hypotension is present in a heterogeneous group of
      disease states, is usually symptomatic, and is often associated with an abnormal
      blood pressure profile of reversal of circadian pattern, postprandial
      hypotension, and noncompensatory heart rate variability. Consequent target organ
      (kidney) damage can be as frequent as in patients who undergo 24-hour ambulatory
      blood pressure monitoring for evaluation of hypertension.

PMID- 15244384
TI  - Durable responses to thalidomide-based drug therapy for myelofibrosis with
      myeloid metaplasia.
AB  - OBJECTIVE: To present the results of a long-term analysis of 2 sequential phase 2
      trials of thalidomide (alone or in combination) for palliation of myelofibrosis
      with myeloid metaplasia (MMM). PATIENTS AND METHODS: We analyzed (March 1999 to
      August 2003) initial and long-term outcomes from 36 patients with symptomatic MMM
      who had enrolled in either our thalidomide single-agent trial (n=15) or our trial
      of low-dose thalidomide (50 mg/d) combined with prednisone (n=21). RESULTS: Among
      the 36 study patients, 20 (56%) showed some improvement in their clinical course.
      Response rates for specific end points included improvements in anemia (15 of 36
      [42%]), thrombocytopenia (10 of 13 [77%]), or splenomegaly (5 of 30 [17%]). The
      combination of low-dose thalidomide and prednisone, as opposed to single-agent
      thalidomide, was better tolerated and more efficacious. After a median follow-up
      of 25 months (range, 20-56 months), 10 of 36 patients (28%) showed an ongoing
      response, including 8 patients in whom protocol treatment has been discontinued
      for a median of 21 months (range, 16-31 months). Durable treatment responses were
      documented for only anemia and thrombocytopenia. Treatment response was not
      affected by the baseline status of bone marrow fibrosis, angiogenesis,
      osteosclerosis, cytogenetics, or circulating myeloid progenitor (CD34) cell
      count. Unusual drug effects, all reversible, included leukocytosis (8 patients)
      and/or thrombocytosis (6 patients). CONCLUSIONS: Thalidomide (alone or combined
      with prednisone) is an effective first-line treatment of symptomatic anemia or
      thrombocytopenia in MMM. Thalidomide-based therapy has the potential to produce
      durable responses in MMM-associated cytopenias, even after discontinuation of the
      drug.

PMID- 15244383
TI  - Thalidomide for patients with relapsed multiple myeloma after high-dose
      chemotherapy and stem cell transplantation: results of an open-label multicenter
      phase 2 study of efficacy, toxicity, and biological activity.
AB  - OBJECTIVES: To determine the progression-free survival at 12 weeks, to evaluate
      the toxic effects, and to analyze the biological activity of thalidomide in
      patients with relapsed multiple myeloma (MM) after high-dose chemotherapy and
      stem cell transplantation. PATIENTS AND METHODS: From 1999 to 2001, we performed
      a multicenter prospective phase 2 study in patients with MM that relapsed after
      high-dose chemotherapy and stem cell transplantation to evaluate the efficacy of
      oral thalidomide, with dose escalation from 200 to 600 mg/d over 12 weeks and a
      subsequent maintenance phase of 200 mg/d for up to 1 year. Outcome was correlated
      with serum and plasma levels of vascular endothelial growth factor and serum
      levels of tumor necrosis factor alpha, soluble intercellular adhesion molecule 1,
      interferon gamma, interleukin (IL) 2, and IL-6 during treatment. RESULTS: Thirty
      patients were treated (19 men and 11 women; median age, 58 years). The median
      number of prior therapies was 5, and the median duration from diagnosis of MM to
      study enrollment was 4.3 years. The 12-week progression-free survival rate was
      67% (95% confidence interval [CI], 48%-86%). The observed response rate (partial
      response plus minor response) was 43% (95% CI, 28%-60%) with a median duration of
      6 months. Attributable toxicities included constipation, fatigue, rash, and
      neuropathy, which was dose limiting in 8 patients (27%). Dose escalation from 200
      to 600 mg/d was achieved in 50% of patients. Although responses were observed
      with lower doses, possibly eliminating the need to escalate the dose, responses
      were also seen in patients who completed the dose escalation. Some patients had
      disease progression while receiving the maintenance dose of 200 mg/d. Analysis of
      biomarker assays did not identify any biomarker associated with greater response,
      but a significant increase in levels of soluble intercellular adhesion molecule
      1, IL-2, and interferon gamma was seen with thalidomide therapy. CONCLUSION: The
      optimal thalidomide dose varies, and adverse effects can be dose limiting. The
      dose of thalidomide therapy should be based on the individual patient to ensure
      that it is well tolerated and that a response is achieved.

PMID- 15244386
TI  - Clinicoradiological features of pulmonary infarctions mimicking lung cancer.
AB  - OBJECTIVE: To describe presenting features of pulmonary infarction that may
      simulate those of lung cancer. PATIENTS AND METHODS: We reviewed the medical
      records of 43 patients with pulmonary infarction diagnosed by surgical lung
      biopsy at the Mayo Clinic in Rochester, Minn, from January 1, 1996, to December
      31, 2002. Of 16 patients presenting with an undiagnosed solitary pulmonary nodule
      or mass, 6 had features suggestive of lung cancer on additional imaging,
      including abnormalities on contrast-enhancement computed tomography (CT),
      positron emission tomography (PET), or nonsurgical lung biopsy before surgical
      resection. We examined the presenting symptoms, epidemiological, clinical, and
      radiological features, and clinical course of these 6 patients. RESULTS: All 6
      patients, ranging in age from 41 to 85 years, had a history of smoking and
      underlying cardiopulmonary disease. In 5 of the 6 patients, CT showed a nodule in
      the subpleural region of the lung. Three patients had abnormalities on contrast
      enhancement CT, 2 had abnormalities on PET, and 1 had abnormal cytologic findings
      on a transthoracic needle biopsy of the lung; all these studies showed
      abnormalities suggestive of lung cancer. Surgical resection of the nodule or mass
      revealed pulmonary infarction associated with organizing thrombi in all 6
      patients. CONCLUSIONS: Pulmonary infarctions can closely mimic the
      clinicoradiological characteristics of lung cancer, an association not reported
      previously. Furthermore, cytologic changes that occur in pulmonary infarctions
      may produce malignant-appearing cells on needle biopsy of the lung. The
      possibility of pulmonary infarction should be considered in the differential
      diagnosis of a solitary lung nodule or mass located in the subpleural region,
      even in the absence of clinically recognized venous thromboembolism.

PMID- 15244387
TI  - Thalidomide: tragic past and promising future.

PMID- 15244388
TI  - The increasing need for anticoagulant therapy to prevent stroke in patients with
      atrial fibrillation.
AB  - Ischemic stroke, a major complication of atrial fibrillation (AF), is believed to
      result from atrial thrombus formation caused by ineffective atrial contraction.
      Oral anticoagulant therapy effectively reduces the risk of ischemic stroke in
      patients with AF; this therapy is recommended for patients with any frequency or
      duration of AF and other risk factors for stroke, such as increased age (>75
      years), hypertension, prior stroke, left ventricular dysfunction, diabetes, or
      heart failure. Recently published data comparing rate-control and rhythm-control
      strategies in AF emphasized the importance of maintaining an international
      normalized ratio higher than 2.0 during warfarin therapy and the need for
      continuing anticoagulant therapy to prevent stroke in high-risk patients, even if
      the strategy is rhythm control. Hemorrhagic complications can be minimized by
      stringent control of the international normalized ratio (particularly in elderly
      patients) and appropriate therapy for comorbidities such as hypertension, gastric
      ulcer, and early-stage cancers. Undertreatment of patients with AF is a
      continuing problem, particularly in the elderly population. Patients perceived as
      likely to be noncompliant, such as the functionally impaired, are less likely to
      receive warfarin therapy. However, stroke prevention with anticoagulants is cost
      effective and improves quality of life, despite the challenges of maintaining
      appropriate anticoagulation with monitoring and warfarin dose titration. New
      medications in development with more predictable dosing and fewer drug-drug
      interactions may reduce the complexities of achieving optimal anticoagulation and
      increase the practicality of long-term anticoagulant therapy for patients with AF
      at risk of stroke.

PMID- 15244389
TI  - Peripheral symmetrical gangrene.

PMID- 15244390
TI  - An algorithm for the management of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a common disorder with a prevalence of 5% to 15%.
      Primary care physicians must become familiar with management of this disorder.
      This algorithm for the management of RLS was written by members of the Medical
      Advisory Board of the Restless Legs Syndrome Foundation and is based on
      scientific evidence and expert opinion. Restless legs syndrome is divided into
      intermittent, daily, and refractory types. Nonpharmacological approaches,
      including mental alerting activities, avoiding substances or medications that may
      exacerbate RLS, and addressing the possibility of iron deficiency, are discussed.
      The role of carbidopa/levodopa, dopamine agonists, opioids, benzodiazepines, and
      anticonvulsants for the different types of the disorder is delineated.

PMID- 15244391
TI  - 70-year-old woman with rash and muscle weakness.

PMID- 15244392
TI  - Linezolid-associated peripheral neuropathy.
AB  - Linezolid is the first drug in a new class of synthetic antimicrobials, the
      oxazolidinones, to be approved by the Food and Drug Administration. Linezolid is
      active against methicillin- and vancomycin-resistant gram-positive
      microorganisms. We describe 2 patients who developed peripheral neuropathy after
      prolonged treatment with linezolid. Linezolid-associated peripheral neuropathy
      has not been well documented. Most reported cases of linezolid-associated
      peripheral neuropathy have occurred in patients who took linezolid for a period
      longer than the recommended 28 or fewer days. Health care providers must be alert
      to the potential for serious adverse effects associated with linezolid use,
      including peripheral neuropathy.

PMID- 15244393
TI  - Tracheal myxoma: a rare benign tracheal tumor.
AB  - Benign tracheal tumors are rare. We describe a 39-year-old man who underwent
      resection of a tracheal myxoma, a previously unrecognized benign tracheal
      neoplasm. He presented with a 9-month history of wheezing, cough, and dyspnea on
      exertion. Treatment with bronchodilators and corticosteroids administered by
      inhalation and systemically did not diminish his symptoms. Pulmonary function
      tests showed a pattern of airflow limitation consistent with variable
      extrathoracic obstruction. Chest radiography and computed tomography revealed a
      tracheal mass. Tracheal resection of the tumor with reconstruction was curative.
      The patient is free of disease 7 years after surgery.

PMID- 15244394
TI  - Introduction to the symposium on cerebrovascular diseases.

PMID- 15244395
TI  - Evaluation and management of asymptomatic carotid artery stenosis.
AB  - Internal carotid artery stenosis (ICAS) is responsible for approximately 30% of
      ischemic strokes. Internal carotid artery stenosis of greater than 50% is present
      in about 4% to 8% of the population aged 50 to 79 years. Natural history studies
      and clinical trials have shown a small increase in stroke risk in patients with
      increasing degrees of ICAS, especially in those with greater than 80% reduction
      in carotid artery diameter. Randomized, prospective multicenter trials have
      revealed the superiority of carotid endarterectomy (CEA) over medical therapy in
      recently symptomatic patients with severe ICAS. However, the evidence from
      several randomized controlled trials of CEA in asymptomatic patients does not
      support the use of CEA in most of these patients; also, the role of noninvasive
      screening in this patient population remains uncertain and controversial.
      Furthermore, there is considerable uncertainty about whether the statistical
      benefit of avoiding a nondisabling stroke is worth the overall cost and risk of
      the procedure. Clinicians continue to struggle with treatment decisions for
      patients with asymptomatic ICAS. Carotid endarterectomy for asymptomatic ICAS
      should be considered only for medically stable patients with 80% or greater
      stenosis who are expected to live at least 5 years, and only in centers with
      surgeons who have a demonstrated low (<3%) perioperative complication rate. We
      outline the prevalence and natural history of ICAS, the evidence for CEA in
      patients with asymptomatic ICAS, the roles of screening and monitoring for ICAS,
      the methods of evaluating ICAS, and the implications for practicing clinicians.

PMID- 15244396
TI  - Morbidity after brachytherapy for prostate adenocarcinoma.

PMID- 15244397
TI  - Morbidity after brachytherapy for prostate adenocarcinoma.

PMID- 15244398
TI  - Morbidity after brachytherapy for prostate adenocarcinoma.

PMID- 15244399
TI  - Rituximab-induced acute pulmonary fibrosis.

PMID- 15244400
TI  - Deciding on transplantation for myelofibrosis: setting the record straight.

PMID- 15244401
TI  - Practical algorithms in anemia diagnosis.

PMID- 15244402
TI  - Steroids and combinatorial chemistry.

PMID- 15244403
TI  - Solid-phase synthesis of alpha-(2-(benzylthio)-1,4-dihydro-6-methyl-4-p
      tolylpyrimidine-5-carboxamido) acids: a new strategy to create diversity in
      heterocyclic scaffolds.

PMID- 15244404
TI  - Efficient synthesis of highly substituted diaryl ethers on solid supports using
      the Ullmann reaction.

PMID- 15244405
TI  - Preparation of poly(ethylene glycol) sulfonamide: synthesis of N-supported beta
      aminoesters via the aza-Baylis-Hillman reaction.

PMID- 15244406
TI  - Solid-supported solution-phase synthesis of 4-amino-1,2,4,5-tetrahydro-2
      benzazepine-3-ones.
AB  - Starting from Boc-o-aminomethylphenylalanine, a solution-phase parallel synthesis
      of 2,4-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described.
      This heterocycle has two nitrogen functions, which are differentiated and can be
      selectively substituted. The sources of diversity are aldehydes for the R(1)
      position and carboxylic acids, sulfonyl chlorides, or isocyanates for the R(2)
      position. High-throughput synthesis and purification of this multistep synthetic
      sequence was accomplished using polymer-bound reagents and scavengers and liquid
      liquid extraction protocols, and a small library of compounds was prepared.
      Polymer-bound cyanoborohydride was found to work well for the reductive
      amination. Scavenging of excess of amine was performed by polymer-bound
      benzaldehyde, and cyclization was performed in the presence of polymer-bound
      coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). After Boc
      deprotection, the second nitrogen can be acylated using carboxylic acids,
      sulfonylated or converted to a urea. The acylation is again performed by polymer
      bound EDC. Excellent yields and purities were obtained.

PMID- 15244407
TI  - Safety-catch approach to orthogonal synthesis of a triazine library.
AB  - A novel safety-catch method for orthogonal synthesis of highly pure
      trisubstituted triazines was developed. Since the polymer-support used in this
      method is not acid-labile, this strategy can be uniquely applied to the synthesis
      of acid-sensitive triazine library compounds. This method will dramatically
      increase the diversity of triazine and other related heterocyclic library
      compounds.

PMID- 15244408
TI  - High-throughput purification of combinatorial libraries II: Automated separation
      of single diastereomers from a 4-amido-pyrrolidone library containing intentional
      diastereomer pairs.
AB  - A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of
      diastereomers was produced by solution-phase parallel syntheses and purified by
      an automated high-throughput purification system. A total of 2592 4-amido
      pyrrolidinones were ultimately isolated as single diastereomers from a matrix of
      1920 syntheses. After the four-step synthesis and HPLC purification, the average
      yield of a single diastereomer was 36.6%. The average chemical purity was >90%,
      and the average diastereomeric purity was >87%. The choice of chiral amines used
      to make amides with heterocyclic acid chlorides had a dramatic effect on success.
      Analysis of the relationship between amines used for synthesis and the
      diastereomeric separation showed that amides made from chiral 1,2-amino alcohols
      gave superior separation to amides from chiral morpholines. The presence of a
      hydrogen bond donor on the amide side chain seems to be required for a better
      diastereomeric separation.

PMID- 15244409
TI  - Solid-phase synthesis of 1-substituted tetrahydroisoquinoline derivatives
      employing BOC-protected tetrahydroisoquinoline carboxylic acids.
AB  - Compounds containing the tetrahydroisoquinoline ring system were prepared using
      solid-supported ester derivatives on a nucleophile-sensitive resin, starting from
      the corresponding BOC-protected amino acids. The key heterocyclic intermediates
      were obtained from the Pictet-Spengler reaction between ethyl glyoxylate or
      methyl 4-formylbenzoate and dopamine or 3-hydroxyphenethylamine. After the
      resulting amino esters were converted to the BOC derivatives, the phenolic
      hydroxyl groups were alkylated with a series of alkyl halides to afford the
      corresponding ethers. Ester hydrolysis afforded the BOC-protected
      tetrahydroisoquinoline carboxylic acid scaffolds, which were then attached to (4
      hydroxyphenyl)sulfide resin (Marshall linker) as the corresponding ester. The BOC
      group was removed under acidic conditions, and the resulting support-bound amine
      hydrochlorides were converted to the corresponding amides using a set of
      carboxylic acids. The support-bound amides were liberated with amines to produce
      the desired tetrahydroisoquinoline carboxamides. Optimization of the resin
      loading conditions is described in addition to the identification of impurities
      observed during the development of the optimum conditions for solid-phase
      synthesis.

PMID- 15244410
TI  - Two dialkoxynaphthalene aldehydes as backbone amide linkers for solid-phase
      synthesis.
AB  - Two new solid-phase handles for backbone amide anchoring based on regioisomeric
      dialkoxynaphthalene aldehydes (NALdehydes) were synthesized in five convenient
      steps from the corresponding commercially available dihydroxynaphthalenes. The
      two NALdehydes were coupled to an aminomethyl polystyrene support, the first
      monomer attached by efficient reductive amination, and the secondary amine
      acylated to form naphthalene amide linker (NAL-1 and NAL-2) anchoring. After on
      resin synthesis, release of peptides was effected with TFA/H(2)O (95:5), TFA/DCM
      (50:50), or low TFA concentrations. The properties of the NAL handles were
      evaluated in the solid-phase synthesis of a series of peptides, in which NAL-2
      showed the best cleavage properties.

PMID- 15244411
TI  - Microwave-assisted parallel synthesis of a 4,6-diamino-2,2-dimethyl-1,2-dihydro-1
      phenyl-s-triazine library.
AB  - Microwave-assisted parallel synthesis of a library of 20 phenyl dihydrotriazines
      was successfully achieved and compared to an identical library generated by
      conventional parallel synthesis. Microwave synthesis dramatically decreased
      reaction times from an average of 22 h to 35 min, and compounds generated using
      microwave irradiation were purer. Isolated yields of all the compounds were
      comparable when the two methods were used.

PMID- 15244412
TI  - Two- and three dimensional combinatorial chemistry from multicomponent Grignard
      reagents.
AB  - The conjugate addition of five component Grignard reagents to methyl ecgonidine
      was used to create libraries of 3-substituted tropanes. By variation in the
      reagent combination in 10 such 5-membered sublibraries, a library of 25 compounds
      was made in a two-dimensional format. Screening of this library led to
      identification of two new potent monoamine transporter ligands that were
      subsequently synthesized. The most potent compound in this library was
      (1R,2S,3S,5S)-3-(3,4-dimethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2
      carboxylic acid methyl ester, which inhibited dopamine transporter (hDAT) binding
      and reuptake with a K(i) of 26 and 20 nM, respectively. The conjugate addition to
      a 5-membered library of methyl ecgonidine analogues with variation of nitrogen
      substituent was also carried out and used to create 15 sublibraries of 25
      compounds, which displayed 125 compounds in a three-dimensional format. From this
      3D library, several potent dopamine transport inhibitors were likewise identified
      and synthesized. The most potent hDAT inhibitor discovered was (1R,2S,3S,5S)-3
      (3,4-dimethylphenyl)-8-pentyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl
      ester. The study also showed that 3-alkyltropanes were poor inhibitors of
      monoamine transporters.

PMID- 15244413
TI  - MS-Express: data-extracting and -processing software for high-throughput
      experimentation with mass spectrometry.
AB  - High-throughput experiments (HTE) result in large amounts of raw data that have
      to be evaluated for sample classification. Especially mass spectrometry, a widely
      used detection method in catalytic HTE applications, produces enormous amounts of
      data. In the past few years, in catalysts research, several test rigs based on
      mass spectrometric detection have been independently reported by different
      groups. In a typical HTE, the catalysts are tested sequentially; the recording of
      the scans, however, occurs continuously. For this reason, the scans of interest
      have to be extracted from the raw data, and scans belonging to the same sample
      have to be averaged in a tedious procedure before further processing. In this
      publication, we present our custom-designed software MS-Express (mass
      spectrometry data-extracting and -processing software), an efficient tool for HTE
      MS data evaluation. MS-Express not only sorts the data, it also establishes
      statistical significance with the help of reference and blank data and provides
      concise information about abundance and intensity distributions of expected
      peaks. A special feature is that the program also reports unexpected MS signals,
      which potentially lead to unexpected discoveries.

PMID- 15244414
TI  - OptiDock: virtual HTS of combinatorial libraries by efficient sampling of binding
      modes in product space.
AB  - Products from combinatorial libraries generally share a common core structure
      that can be exploited to improve the efficiency of virtual high-throughput
      screening (vHTS). In general, it is more efficient to find a method that scales
      with the total number of reagents (Sigma growth) rather with the number of
      products (Pi growth). The OptiDock methodology described herein entails selecting
      a diverse but representative subset of compounds that span the structural space
      encompassed by the full library. These compounds are docked individually using
      the FlexX program (Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. J. Mol. Biol.
      1995, 251, 470-489) to define distinct docking modes in terms of reference
      placements for combinatorial core atoms. Thereafter, substituents in R-cores
      (consisting of the core structure substituted at a single variation site) are
      docked, keeping the core atoms fixed at the coordinates dictated by each
      reference placement. Interaction energies are calculated for each docked R-core
      with respect to the target protein, and energies for whole compounds are
      calculated by finding the reference core placement for which the sum of
      corresponding R-core energies is most negative. The use of diverse whole
      compounds to define binding modes is a key advantage of the protocol over other
      combinatorial docking programs. As a result, OptiDock returns better-scoring
      conformers than does serially applied FlexX. OptiDock is also better able to find
      a viable docked pose for each library member than are other combinatorial
      approaches.

PMID- 15244415
TI  - Designing a multiroute synthesis scheme in combinatorial chemistry.
AB  - Solid-phase mix-and-split combinatorial synthesis is often used to produce large
      arrays of compounds to be tested during the various stages of the drug
      development process. This method can be represented by a synthesis graph in which
      nodes correspond to grow operations and arcs to beads transferred among the
      different reaction vessels. In this work, we address the problem of designing
      such a graph which maximizes the number of produced target compounds (namely,
      compounds out of an input library of desired molecules), given constraints on the
      number of beads used for library synthesis and on the number of reaction vessels
      available for concurrent grow steps. We present a heuristic based on a discrete
      search for solving this problem, test our solution on several data sets, explore
      its behavior, and show that it achieves good performance.

PMID- 15244416
TI  - Device for preparing combinatorial libraries in powder metallurgy.
AB  - This paper describes a powder-metering, -mixing, and -dispensing mechanism that
      can be used as a method for producing large numbers of samples for metallurgical
      evaluation or electrical or mechanical testing from multicomponent metal and
      cermet powder systems. It is designed to make use of the same commercial powders
      that are used in powder metallurgy and, therefore, to produce samples that are
      faithful to the microstructure of finished products. The particle assemblies
      produced by the device could be consolidated by die pressing, isostatic pressing,
      laser sintering, or direct melting. The powder metering valve provides both
      on/off and flow rate control of dry powders in open capillaries using acoustic
      vibration. The valve is simple and involves no relative movement, avoiding
      seizure with fine powders. An orchestra of such valves can be arranged on a
      building platform to prepare multicomponent combinatorial libraries. As with many
      combinatorial devices, identification and evaluation of sources of mixing error
      as a function of sample size is mandatory. Such an analysis is presented.

PMID- 15244417
TI  - Potential protease inhibitors based on a functionalized cyclic sulfamide
      scaffold.
AB  - Exploratory studies related to the design and synthesis of functionalized cyclic
      sulfamides (I) as potential inhibitors of proteolytic enzymes were carried out.
      The structural motif and three diversity sites embodied in the scaffold render it
      amenable to combinatorial parallel synthesis and the facile generation of lead
      discovery prospecting libraries. The scaffold was readily assembled starting with
      (DL) serine methyl ester, and a series of compounds was generated and screened
      against human leukocyte elastase. Modification of the P(1) recognition element,
      believed to be accommodated at the primary specificity site (S(1) subsite) of the
      enzyme, yielded compounds that inhibited the enzyme by an apparent hyperbolic
      partial mixed-type inhibition.

PMID- 15244418
TI  - Solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline derivatives employing
      support-bound tyrosine esters in the Pictet-Spengler reaction.
AB  - The solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline-3-carboxamides
      employing carboxyl-supported, o-alkylated tyrosine esters in a Pictet-Spengler
      reaction is described. Esterification of [4-(hydroxyphenyl)thiomethyl]polystyrene
      (Marshall resin) with ethers of N-BOC-L-tyrosine using diisopropylcarbodiimide
      (DIC) and 4-dimethylaminopyridine (4-DMAP) afforded the solid-supported ester
      derivatives. Removal of the BOC group with trifluoroacetic acid (TFA) afforded
      the carboxyl-supported tyrosine ester, which was then treated with
      paraformaldehyde and TFA to afford the desired solid-supported counterpart.
      Acylation of the secondary amine with arylsulfonyl chlorides followed by reaction
      with amines resulted in the formation of the desired 2-arylsulfonyl-7-alkoxy
      1,2,3,4-tetrahydroisoquinoline-3-carboxamides. Alternatively, the support-bound
      tetrahydroisoquinoline-3-carboxylate derivatives could be treated with an
      aldehyde and a reducing agent to give the corresponding support-bound tertiary
      amine. Exposure of these resin-bound products to amines afforded the
      corresponding 2-alkyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides
      after cleavage from the resin. Alternative routes to the desired chemotypes, as
      well optimization of the conditions for the Pictet-Spengler reaction and the
      conditions for the acylation and reductive amination of the support-bound
      secondary amines, are also described.

PMID- 15244419
TI  - Synthesis of substituted thienopyrimidine-4-ones.
AB  - The parallel solution-phase synthesis of more than 3000 substituted
      thienopyrimidin-4-ones has been accomplished. Key reactions include assembly of
      the 2-thioxopyrimidin-4-one ring by condensation of isomeric
      aminothiophenecarboxylates or their appropriate reactive derivatives
      (isothiocyanates or dithiocarbamates) with the corresponding isothiocyanates or
      amines. The libraries from libraries were then obtained in good yields and
      purities using solution-phase alkylation and acylation methodologies. Simple
      manual techniques for parallel reactions using special CombiSyn synthesizers were
      coupled with easy purification procedures (crystallization from the reaction
      mixtures) to give high-purity final products. The scope and limitations of the
      developed approach are discussed.

PMID- 15244420
TI  - Automated flow-through synthesis of heterocyclic thioethers.
AB  - The fully automated, sequential flow-through synthesis of a 44-member array of
      thioethers 10[1-4,1-11] employing a resin "capture and release" reactor column is
      described. The array incorporates four different heterocyclic scaffolds, and the
      synthesis was performed using a custom-built robotic synthesizer that is able to
      (i) load and regenerate the reactor column and (ii) array each product into a
      single vial using UV threshold detection. All the compounds were obtained in high
      yield (>75%) and excellent purity (>95%) without the need for further
      purification.

PMID- 15244421
TI  - Anomalous regioselective four-member multicomponent Biginelli reaction II: one
      pot parallel synthesis of spiro heterobicyclic aliphatic rings.
AB  - In a previous preliminary study, we found that a cyclic five-member ring beta
      keto ester (lactone) reacts with one molecule of urea and two of aldehyde to give
      a new family of spiro heterobicyclic aliphatic rings in good yields with no
      traces of the expected dihydropyrimidine (Biginelli) products. The reaction is
      driven by a regiospecific condensation of two molecules of aldehyde with urea and
      beta-keto-gamma-lactone to afford only products harboring substitutions
      exclusively in a syn configuration (Byk, G.; Gottlieb, H. E.; Herscovici, J.;
      Mirkin, F. J. Comb. Chem. 2000, 2, 732-735). In the present work ((a) Presented
      in part at ISCT Combitech, October 15, 2002, Israel, and Eurocombi-2, Copenhagen
      2003 (oral and poster presentation). (b) Also in American Peptide Society
      Symposium, Boston, 2003 (poster presentation). (c) Abstract in Biopolymers 2003,
      71 (3), 354-355), we report a large and exciting extension of this new reaction
      utilizing parallel organic synthesis arrays, as demonstrated by the use of chiral
      beta-keto-gamma-lactams, derived from natural amino acids, instead of tetronic
      acid (beta-keto-gamma-lactone) and the potential of the spirobicyclic products
      for generating "libraries from libraries". Interestingly, we note an unusual and
      important anisotropy effect induced by perpendicular interactions between rigid
      pi systems and different groups placed at the alpha position of the obtained
      spirobicyclic system. Stereo/regioselectivity of the aldehyde condensation is
      driven by the nature of the substitutions on the starting beta-keto-gamma-lactam.
      Aromatic aldehydes can be used as starting reagents with good yields; however,
      when aliphatic aldehydes are used, the desired products are obtained in poor
      yields, as observed in the classical Biginelli reaction. The possible reasons for
      these poor yields are addressed and clarify, to some extent, the complexity of
      the Biginelli multicomponent reaction mechanism and, in particular, the mechanism
      of the present reaction. Finally, we have investigated and proposed a mechanism
      for this new reaction by intercepting several intermediates.

PMID- 15244423
TI  - A fluorous-tagged, acid-labile protecting group for the synthesis of carboxamides
      and sulfonamides.
AB  - A new acid-labile, fluorous-tagged protecting group that facilitates the
      preparation of carboxamides and sulfonamides by parallel solution-phase synthesis
      is introduced. Its use is exemplified by the preparation of a 27-member library
      of biaryl sulfonamides and an 18-member library of biaryl carboxamides.
      Intermediates were purified by solid-phase extraction over reversed-phase
      fluorous silica gel to afford library members in high yields and purities (>95%)
      without the need for column chromatographic purification.

PMID- 15244422
TI  - Solid-phase synthesis and spectral properties of 2-alkylthio-6H-pyrano[2,3
      f]benzimidazole-6-ones: a combinatorial approach for 2-alkylthioimidazocoumarins.
AB  - The solid-phase synthesis of 2-alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones (2
      alkylthioimidazocoumarins) is described. 7-Fluoro-4-methyl-6-nitro-2-oxo-2H-1
      benzopyran-3-carboxylic acid was coupled to Rink amide resin via its carboxyl
      group. The resin-bound scaffold then underwent aromatic nucleophilic substitution
      with primary amines, followed by reduction of the nitro group with tin (II)
      chloride. Subsequent cyclization of the o-dianilino intermediates with
      thiocarbonyldiimidazole (TCD) afforded resin-bound 1,3-dihydro-2-thioxo-6H
      pyrano[2,3-f]benzimidazole-6-ones, which were then S-alkylated with alkyl halides
      in the presence of N,N-diisopropylethylamine (DIEA). The desired products were
      obtained in good yield with high purity after trifluoroacetic acid cleavage. The
      unique spectral properties of 2-alkylthioimidazocoumarins indicate that they may
      be useful in photodynamic therapy.

PMID- 15244424
TI  - Biomedical application of commercial polymers and novel polyisobutylene-based
      thermoplastic elastomers for soft tissue replacement.
AB  - Novel polyisobutylene-based thermoplastic elastomers are introduced as
      prospective implant materials for soft tissue replacement and reconstruction. In
      comparison, poly(ethylene terephthalate) (PET), poly(tetrafluoroethylene) (PTFE),
      polypropylene (PP), polyurethanes (PU), and silicones are outlined from well
      established implant history as being relatively inert and biocompatible
      biomaterials for soft tissue replacement, especially in vascular grafts and
      breast implants. Some general considerations for the design and development of
      polymers for soft tissue replacement are reviewed from the viewpoint of material
      science and engineering, with special attention to synthetic materials used in
      vascular grafts and breast implants.

PMID- 15244425
TI  - Role of substituents on the properties of some polysaccharides.
AB  - This paper concerns the influence of the chemical structure on the physical
      properties of some polysaccharides. Especially, we proposed to discuss the role
      of the substituents on these properties. In some cases, non-carbohydrate
      substituents play a minor role on rheological properties in the presence of a
      salt excess as shown on xanthan and succinoglycan. The rheology of aqueous
      solution of these stereoregular polysaccharides is controlled by the conformation
      (helical conformation) whose stability is not largely influenced by these
      substituents. On the other hand, the interaction between galactomannan and
      xanthan depends on the presence of acetyl substituents on xanthan but also on the
      xanthan conformation. However, for polymers such as gellan, XM-6 or BEC 1615,
      complete deacetylation induces the ability to form physical gels in given
      thermodynamic conditions. The presence of carbohydrate substituents or short side
      chains was also examined. Especially in the gellan family, the role of position
      of substitution (position 3 on the glucose unit C or position 6 on the A glucose)
      was presented. It is concluded that the substituents giving the higher stability
      for the helical conformation (higher DeltaH and Tm values) also cause a lower
      salt sensitivity for the helical stability. The role of the substituents on the
      properties is also described for natural polymers and their chemically or
      enzymatically modified derivatives.

PMID- 15244426
TI  - Microbial degradation of poly(amino acid)s.
AB  - Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with
      various biological functions and putative technical applications and play,
      therefore, an important role both in nature and in human life. Because of their
      biocompatibility and their synthesis from renewable resources, poly(amino acid)s
      may be employed for many different purposes covering a broad spectrum of medical,
      pharmaceutical, and personal care applications as well as the domains of
      agriculture and of environmental applications. Biodegradability is one important
      advantage of naturally occurring poly(amino acid)s over many synthetic polymers.
      The intention of this review is to give an overview about the enzyme systems
      catalyzing the initial steps in poly(amino acid) degradation. The focus is on the
      naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and
      poly(gamma-glutamic acid); but biodegradation of structurally related synthetic
      polyamides such as poly(aspartic acid) and nylons, which are known from various
      technical applications, is also included.

PMID- 15244427
TI  - Facile, controlled, room-temperature RAFT polymerization of N
      isopropylacrylamide.
AB  - Poly(N-isopropyl acrylamide) is a thermoresponsive polymer that has been widely
      investigated for drug delivery. Herein, we report conditions facilitating the
      controlled, room-temperature RAFT polymerization of N-isopropylacrylamide
      (NIPAM). The key to success is the appropriate choice of both a suitable RAFT
      chain transfer agent (CTA) and initiating species. We show that the use of 2
      dodecylsulfanylthiocarbonylsulfanyl-2-methyl propionic acid, a trithiocarbonate
      RAFT CTA, in conjunction with the room-temperature azo initiator 2,2'-azobis(4
      methoxy-2,4-dimethylvaleronitrile), in DMF, at 25 degrees C, yields conditions
      leading to NIPAM homopolymerizations which bear all of the characteristics of a
      controlled/"living" polymerization. We also demonstrate facile size exclusion
      chromatographic analysis of PNIPAM samples in DMF at 60 degrees C, directly on
      aliquots withdrawn during the polymerizations, which avoids the problems
      previously reported in the literature.

PMID- 15244428
TI  - Stereocomplex formation between enantiomeric poly(lactic acid)s. 12. spherulite
      growth of low-molecular-weight poly(lactic acid)s from the melt.
AB  - The spherulite growth of stereocomplex crystallites in the blend from low
      molecular-weight poly(L-lactide) [i.e., poly(L-lactic acid) (PLLA)] and poly(D
      lactide) [i.e., poly(D-lactic acid) (PDLA)] from the melt, together with that of
      the homocrystallites in pure PLLA and PDLA films, was investigated using
      polarization optical miscroscopy. The spherulite growth of stereocomplex
      crystallites occurred at a wider temperature range (</=190 degrees C) compared
      with that of homocrystallites (</=140 degrees C). At 140 degrees C, the
      spherulite radius growth rate (G) for the stereocomplex crystallites (136.4
      microm min(-1)) was an order of magnitude higher than those for the
      homocrystallites of PLLA (11.8 microm min(-1)) and PDLA (15.7 microm min(-1)),
      whereas the induction period was shorter for the spherulties of stereocomplex
      crystallites (0.0 min) than for the spherulties of homocrystallites of PLLA (2.6
      min) and PDLA (0.7 min). In addition to these two factors, the higher spherulite
      density of stereocomplex crystallites compared with those of the homocrystallites
      of PLLA and PDLA resulted in rapid completion of overall crystallization of
      stereocomplex. The front factor (G(0)) and nucleation constant (K(g)) for the
      stereocomplex crystallites in the temperature range of 140-190 degrees C were
      estimated to be 3.56 x 10(12) microm min(-1) and 8.42 x 10(5) K(2), respectively.
      The G(0) value for stereocomplex crystallites was 1 and 2 orders of magnitude
      higher than those for the homocrystallites of PLLA (9.69 x 10(11) microm min(-1))
      and PDLA (8.79 x 10(10) microm min(-1)), whereas the K(g) value for stereocomplex
      crystallites was twice those for the homocrystallites of PLLA (4.95 x 10(5) K(2))
      and PDLA (4.20 x 10(5) K(2)).

PMID- 15244429
TI  - Effect of water on the surface molecular mobility of poly(lactide) thin films: an
      atomic force microscopy study.
AB  - Physical properties associated with molecular mobility on the surface of thin
      films with 300 nm thickness for poly(lactide)s (PLAs) were studied under vacuum
      conditions as well as under aqueous conditions by using friction force mode
      atomic force microscopy (AFM). Two types of PLAs were applied for the
      experimental samples as uncrystallizable PLA (uc-PLA) and crystallizable PLA (c
      PLA). The friction force on the surface of thin films was measured as a function
      of temperature to assess the surface molecular mobility both under vacuum and
      under aqueous conditions. A lower glass-transition temperature of the uc-PLA
      surface in water was detected than that under vacuum conditions. In the case of
      the c-PLA thin film, change in friction force was detected at a lower temperature
      under aqueous conditions than in vacuo. A morphological change was observed in
      the c-PLA thin film during heating process from room temperature to 100 degrees C
      by temperature-controlled AFM. The surface of the c-PLA thin film became rough
      due to the cold crystallization, and the crystallization of c-PLA molecules in
      water took place at a lower temperature than in vacuo. These friction force
      measurements and AFM observations suggest that molecular motion on the surface of
      the both uc- and c-PLA thin films is enhanced in the presence of water molecules.
      In addition, in situ AFM observation of the enzymatic degradation process for the
      c-PLA thin film crystallized at 160 degrees C was carried out in buffer solution
      containing proteinase K at room temperature. The amorphous region around the
      hexagonal crystal was eroded within 15 min. It has been suggested that the
      adsorption of water molecules on the PLA film surface enhances the surface
      molecular mobility of the glassy amorphous region of PLA and induces the
      enzymatic hydrolysis by proteinase K.

PMID- 15244430
TI  - Investigation into the diffusion of water into HEMA-co-MOEP hydrogels.
AB  - Cross-linked homopolymers and copolymers of 2-hydroxyethyl methacrylate, HEMA,
      and ethylene glycol methacrylate phosphate, MOEP, have been synthesized, and the
      diffusion of water into these systems has been investigated. Only polymers with 0
      20 mol % MOEP exhibited ideal swelling behavior as extensive fracturing occurred
      in the systems with greater than 20 mol % MOEP as the polymers began to swell
      during water sorption. Gravimetric studies were used in conjunction with magnetic
      resonance imaging of the diffusion front to elucidate the diffusion mechanism for
      these systems. In the case of the cross-linked HEMA homopolymer gels, the water
      transport mechanism was determined to be concentration-independent Fickian
      diffusion. However, as the fraction of MOEP in the network increased, the
      transport mechanism became increasingly exponentially concentration-dependent but
      remained Fickian until the polymer consisted of 30 mol % MOEP where the water
      transport could no longer been described by Fickian diffusion.

PMID- 15244431
TI  - Bio-based polymeric composites comprising wood flour as filler.
AB  - The increasing effort on development of bio-based polymeric materials in recent
      years is motivated by the basic concept of meeting the sustainability criteria
      for industrial development in the third millennium. Within this framework, our
      research group is currently involved in assessing the potentiality of some agro
      industrial overproduction and byproducts in the formulation of eco-compatible bio
      based polymeric materials displaying, among others, the propensity to biodegrade
      under controlled environment conditions. In the present work, beech wood flour
      (Bwf) composites were prepared from plasticized poly(3-hydroxybutyrate) (PHB).
      The type of plasticizer [tri(ethylene glycol) bis(2-ethylhexanoate) (TEGB) and
      poly(ethylene glycol) (PEG200)] and the amount [5 and 20 wt %] were selected as
      independent variables in a factorial design. Thermal and mechanical properties of
      90 wt % PHB composites were investigated. Incorporation of PEG200 was found to
      compromise thermal stability of PHB as demonstrated by the higher decrease on the
      onset decomposition temperature (T(d)) and the drop in its average molecular
      weight (M(w)). The present study underlines the fact that TEGB/PHB/beech wood
      flour composites can be optimized to obtain new materials for disposable items.

PMID- 15244432
TI  - Gelation of xyloglucan by addition of epigallocatechin gallate as studied by
      rheology and differential scanning calorimetry.
AB  - Interaction of tamarind seed xyloglucan (TSX) and epigallocatechin gallate (EGCG)
      was investigated. TSX alone showed the rheological behaviors of dilute and
      semidilute solution types in the temperature range from 10 to 50 degrees C and
      the concentration range from 1 to 10%. Addition of a small amount of EGCG changed
      the rheological properties of TSX solutions to induce a thermoreversible
      gelation. The sol-gel transition was detected as a crossover of the storage and
      loss shear moduli at a certain temperature in thermal scanning rheological
      measurements and an endo- and exo- thermic peaks in curves obtained by
      differential scanning calorimetry on heating and cooling. High storage modulus of
      the gels at all experimental frequencies also indicated the formation of a
      network structure. Increase in the gel strength and the enthalpy of the
      transition with increasing EGCG concentration at fixed TSX concentration
      suggested that EGCG was directly involved in the network formation through
      association with TSX. The TSX gel was obtained by addition of appropriate amount
      of EGCG. Addition of an excessive amount of EGCG induced precipitation.

PMID- 15244433
TI  - Solvent specified conformation in poly(alpha-L-glutamic acid) thin films.
AB  - The ability to control conformational properties of polypeptides in their films
      is of considerable interest for many possible applications of these materials. By
      rational choice of the solvent system for film fabrication, control over the
      conformation of the main chain, the intermolecular hydrogen bonding in the side
      chain is easily achieved in poly(alpha-L-glutamic acid) (PLGA) thin films. The
      spectral data from circular dichromism (CD), FT-IR, and solid state (13)C NMR
      spectroscopies suggest that the beta-sheet conformation is dominant in PLGA films
      cast from trifluoroacetic acid (TFA) solution, whereas the right-handed alpha
      helix is dominant in those cast from pyridine or DMF solution. In comparison with
      films cast from TFA solutions, the films fabricated from pyridine or DMF
      solutions exhibit strong intermolecular hydrogen bondings between -COOH groups
      and have a more ordered arrangement of side chains. Moreover, the extent of alpha
      helix conformation of the PLGA backbone in films cast from pyridine or DMF
      solution is several times higher than that observed in the PLGA powder
      precipitated from aqueous solution at pH 4. All spectroscopic studies indicate
      clearly that the solvents (used for casting these films) play a crucial role in
      directing the organization of PLGA in these thin films.

PMID- 15244434
TI  - Spectroscopic study of extracellular polymeric substances from Bacillus subtilis:
      aqueous chemistry and adsorption effects.
AB  - Reactions at ionizable functional groups in extracellular polymeric substances
      (EPS) from Bacillus subtilis are found to affect aqueous phase conformation and
      adsorption to mineral surfaces. Characterization by HPSEC, XPS, and FTIR
      indicates a wide range in apparent molecular mass (0.57-128 kDa), with functional
      group composition depending on cell growth phase (exponential vs stationary) and
      location in suspension (free vs cell-bound). ATR-FTIR spectroscopy shows
      complexation and dissociation of protons on acidic functional groups that result
      in alpha-helical protein conformation at pH < 2.6 and random coil (unordered)
      conformation at higher pH (>6). EPS exhibit higher affinity for adsorption to
      alpha-FeOOH than amorphous SiO(2) because of surface charge effects. Increased
      amide II band intensity and an amide I band shift to higher frequency indicate
      changes in protein structure upon adsorption. Goethite-EPS spectra show emergent
      vibrations consistent with P-O-Fe bonding, which suggests a role of
      phosphodiester groups in the adsorption reaction.

PMID- 15244435
TI  - External chirality-triggered helicity control promoted by introducing a beta-Ala
      residue into the N-terminus of chiral peptides.
AB  - The noncovalent chiral domino effect (NCDE), defined as chiral interaction upon
      an N-terminus of a 3(10)-helical peptide, will provide a unique method for
      structural control of a peptide helix through the use of external chirality. On
      the other hand, the NCDE has not been considered to be effective for the helicity
      control of peptides strongly favoring a one-handed screw sense. We here aim to
      promote the NCDE on peptide helicity using two types of nonapeptides: H-beta-Ala
      Delta(Z)Phe-Aib-Delta(Z)Phe-X-(Delta(Z)Phe-Aib)(2)-OCH(3) [Delta(Z)Phe =
      alpha,beta-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], where X as
      the single chirality is L-leucine (1) or L-phenylalanine (2). NMR, IR, and CD
      spectroscopy as well as energy calculation revealed that both peptides alone form
      a right-handed 3(10)-helix. The original CD amplitudes or signs in chloroform,
      irrespective of a strong screw-sense preference in the central chirality,
      responded sensitively to external chiral information. Namely added Boc-L-amino
      acid stabilized the original right-handed helix, while the corresponding d-isomer
      destabilized it or transformed it into a left-handed helix. These peptides were
      also shown to bind more favorably to an L-isomer from the racemate. Although
      similar helicity control was observed for analogous nonapeptides bearing an N
      terminal Aib residue (Inai, Y.; et al. Biomacromolecules 2003, 4, 122), the
      present findings demonstrate that the N-terminal replacement by the beta-Ala
      residue significantly improves the previous NCDE to achieve more effective
      control of helicity. Semiempirical molecular orbital calculations on complexation
      of peptide 2 with Boc-(L or D)-Pro-OH reasonably explained the unique
      conformational change induced by external chirality.

PMID- 15244436
TI  - Improving the environment for immobilized dehydrogenase enzymes by modifying
      Nafion with tetraalkylammonium bromides.
AB  - Recent research in our group has shown that mixture-casting Nafion with
      quaternary ammonium bromides can increase the electrochemical flux of redox
      couples through the membrane and allow for larger redox species to diffuse to the
      electrode surface. The research has also suggested that when these salts are cast
      with Nafion micellar pore size is changing. Therefore, it was proposed that the
      quaternary ammonium salts could be employed to tailor the structure of the Nafion
      membrane for immobilizing enzymes in the polymer. For cations with a high
      affinity for the sulfonic acid groups of Nafion, the modified structure of Nafion
      can also help to stabilize the enzyme and increase activity by providing a
      protective outer shell and an ideal chemical environment that resists a decrease
      in pH within the pore structure. This research examines the ability to immobilize
      dehydrogenase enzymes in Nafion that has been modified with quaternary ammonium
      bromides. Fluorescence assays, fluorescence microscopy, and cyclic voltammetric
      studies were employed to analyze the ability to immobilize an enzyme within the
      membrane, to determine the activity of the immobilized enzyme and to examine the
      transport of coenzyme within the membrane. Dehydrogenase enzymes immobilized in
      tetrabutylammonium bromide/Nafion membranes have shown high catalytic activity
      and enzyme active lifetimes of greater than 45 days. A variety of dehydrogenase
      enzymes have been successfully immobilized in the membrane, including: alcohol
      dehydrogenase, aldehyde dehydrogenase, glucose dehydrogenase, and lactic
      dehydrogenase.

PMID- 15244437
TI  - Characterization of nanostructure of stimuli-responsive polymeric composite
      membranes.
AB  - To elucidate the mechanism of stimuli-responsive permeability and to optimize the
      design, the nanostructure of polymeric composite membranes, developed in our
      laboratory, was characterized. The membranes were prepared to contain various
      amounts of stimuli-responsive nanoparticles of poly(N-isopropylacrylamide-co
      methacrylic acid), with or without polyelectrolyte coating. Scanning electron
      microscopy and X-ray photoelectron spectroscopy were used respectively to examine
      the morphology and surface chemical composition, whereas atomic force microscopy
      and laser scanning confocal microscopy were employed to characterize the in situ
      surface and internal structure of the membranes in aqueous media of various pHs.
      The porous structure was evidenced in the presence of the nanoparticles. The
      surface content of the nanoparticles increased with increasing particle
      concentration while the polyelectrolyte coating was nearly undetectable. AFM
      images revealed that the particles in the membranes shrank with a concomitant
      increase in pore size as the buffer pH decreased. LSCM results indicated that
      particles were distributed through the membrane as interconnected clusters.

PMID- 15244438
TI  - Nanostructures of complexes formed by calf thymus DNA interacting with cationic
      surfactants.
AB  - Synchrotron small-angle X-ray scattering was used to study the nanostructures of
      the complexes formed by calf thymus DNA interacting with cationic lipids (or
      surfactants) of didodecyldimethylammonium bromide (DDAB), cetyltrimethylammonium
      bromide (CTAB), and their mixture with a zwitterionic lipid of 1-palmitoyl-2
      hydroxy-sn-glycero-3-phosphocholine (PHGPC). The effects of lipid/DNA ratios, DNA
      chain flexibility, lipid topology, and neutral lipid mixing on the nanostructures
      of DNA-lipid complexes were investigated. The complexes between double-stranded
      DNA (dsDNA) and double-tailed DDAB formed a bilayered lamellar structure, whereas
      the complexes between dsDNA and single-tailed CTAB preferred a structure of 2D
      hexagonal close packing of cylinders. With single stranded DNA (ssDNA)
      interacting with CTAB, the complexes showed a Pm3n cubic structure due to the
      different chain flexibility between dsDNA and ssDNA. The lipid molecules bound by
      rigid dsDNA like to form cylindrical micelles, whereas lipids bound to flexible
      ssDNA could form spherical or short cylindrical micelles. The addition of the
      neutral single-chained PHGPC lipids to the CTAB lipids could induce a structural
      transition of dsDNA-lipid complexes from a 2D hexagonal to a multi-bilayered
      lamellar structure. The parallel DNA strands were intercalated in the water
      layers of lamellar stacks of the mixed lipid bilayers. The DNA-DNA spacing
      depended on the ratios of charged lipid to neutral lipid, and charged lipid to
      DNA, respectively.

PMID- 15244439
TI  - Designing new materials from wheat protein.
AB  - We recently discovered that wheat gluten could be formed into a tough,
      plasticlike substance when thiol-terminated, star-branched molecules are
      incorporated directly into the protein structure. This discovery offers the
      exciting possibility of developing biodegradable high-performance engineering
      plastics and composites from renewable resources that are competitive with their
      synthetic counterparts. Wheat gluten powder is available at a cost of less than
      dollars 0.5/lb, so if processing costs can be controlled, an inexpensive
      alternative to synthetic polymers may be possible. In the present work, we
      demonstrate the ability to toughen an otherwise brittle protein-based material by
      increasing the yield stress and strain-to-failure, without compromising
      stiffness. Water absorption results suggest that the cross-link density of the
      polymer is increased by the presence of the thiol-terminated, star-branched
      additive in the protein. Size-exclusion high performance liquid chromatography
      data of molded tri-thiol-modified gluten are consistent with that of a polymer
      that has been further cross-linked when compared directly with unmodified gluten,
      handled under identical conditions. Remarkably, the mechanical properties of our
      gluten formulations stored in ambient conditions were found to improve with time.

PMID- 15244440
TI  - Mechanical properties of biomimetic tissue adhesive based on the microbial
      transglutaminase-catalyzed crosslinking of gelatin.
AB  - Fibrin sealants are a type of soft tissue adhesive that employs biochemical
      reactions from the late stages of the blood coagulation cascade. Intrinsic to
      these adhesives are a structural protein and a transglutaminase crosslinking
      enzyme. We are investigating an alternative biomimetic adhesive based on gelatin
      and a calcium-independent microbial transglutaminase (mTG). Rheological
      measurements show that mTG catalyzes the conversion of gelatin solutions into
      hydrogels, and gel times are on the order of minutes depending on the gelatin
      type and concentration. Tensile static and dynamic loading of the adhesive
      hydrogels in bulk form demonstrated that the Young's modulus ranged from 15 to
      120 kPa, and these bulk properties were comparable to those reported for
      hydrogels obtained from fibrin-based sealants. Lap-shear adhesion tests of
      porcine tissue were performed using a newly published American Society for
      Testing and Materials (ASTM) standard for tissue adhesives. The gelatin-mTG
      adhesive bound the opposing tissues together with ultimate adhesive strengths of
      12-23 kPa which were significantly higher than the strength observed for fibrin
      sealants. Even after failure, strands of the gelatin-mTG adhesive remained
      attached to both of the opposing tissues. These results suggest that gelatin-mTG
      adhesives may offer the benefits of fibrin sealants without the need for blood
      products.

PMID- 15244441
TI  - Synthesis and characterization of PEG dimethacrylates and their hydrogels.
AB  - Facile synthesis and detailed characterization of photopolymerizable and
      biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene
      glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s
      of various molecular masses (M(n) = 1000 to 8000 g/mol) were reacted with
      methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and
      PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to
      achieve fast reaction conversions under solvent free conditions. Combined
      analyses of (1)H NMR and MALDI-TOF MS confirmed the formation of prepolymers of
      high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the
      PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield
      hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the
      biocompatibility. Preliminary rheology and uniaxial compression measurements
      showed varied mechanical response, and biocompatibility studies showed that cells
      are completely viable in both types of hydrogels after two weeks.

PMID- 15244442
TI  - Single-molecular pair unbinding studies of Mannuronan C-5 epimerase AlgE4 and its
      polymer substrate.
AB  - Alginate biosynthesis involves C-5-mannuronan epimerases catalyzing the
      conversion of beta-D-mannuronic acid to alpha-L-guluronic acid at the polymer
      level. Mannuronan epimerases are modular enzymes where the various modules yield
      specific sequential patterns of the converted residues in their polymer products.
      Here, the interaction between the AlgE4 epimerase and mannuronan is determined by
      dynamic force spectroscopy. The specific unbinding between molecular pairs of
      mannuronan and AlgE4 as well as its two modules, A and R, respectively, was
      studied as a function of force loading rate. The mean protein-mannuronan
      unbinding forces were determined to be in the range 73-144 pN, depending on the
      protein, at a loading rate of 0.6 nN/s, and increased with increasing loading
      rate. The position of the activation barrier was determined to be 0.23 +/- 0.04
      nm for the AlgE4 and 0.10 +/- 0.02 nm for its A-module. The lack of interaction
      observed between the R-module and mannuronan suggest that the A-module contains
      the binding site for the polymer substrate. The ratio between the epimerase
      mannuronan dissociation rate and the catalytic rate for epimerization of single
      hexose residues suggests a processive mode of action of the AlgE4 epimerase
      yielding the observed sequence pattern in the uronan associated with the A-module
      of this enzyme.

PMID- 15244443
TI  - Volume phase transition of bovine vitreous body in vitro and determination of its
      dynamics.
AB  - The phase equilibrium property and structural and dynamical properties of bovine
      vitreous body was studied by macroscopic observation of swelling behavior and
      dynamic light scattering under various conditions. It was found that the vitreous
      body collapses into a compact state isotropically or anisotropically depending on
      the external conditions. The vitreous body collapses while maintaining the shape
      when the pH (</= 4) and the concentration of calcium ions (</= 1 mol/L) are
      changed, whereas it collapses along the orbital axis in a mixed solvent of
      methanol and water. From observations of the dynamics of light scattered by the
      vitreous body, intensity autocorrelation functions that revealed two independent
      diffusion coefficients, D(fast) = 7.8 +/- 1.5 x 10 (- 8) cm(2)/s and D(slow) =
      3.8 +/- 0.60 x 10 (-9) cm(2)/s, were obtained. The diffusion coefficients were
      found to be statistically independent of position within a focal depth range of 1
      1.5 mm. Divergent behavior in the measured total scattered light intensities and
      diffusion coefficients was observed as the concentration of calcium ion
      approached the critical threshold, 1 mol/L. Namely, a slowing down of the dynamic
      modes accompanied by increased "static" scattered intensities was observed. The
      divergent behavior in the scattered light intensities and diffusion coefficients
      was reversible. This is indicative of the occurrence of a phase transition upon
      calcium ion concentration.

PMID- 15244444
TI  - Morphology of elastic poly(L-lactide-co-epsilon-caprolactone) copolymers and in
      vitro and in vivo degradation behavior of their scaffolds.
AB  - Very elastic PLCL [poly(L-lactide-co-epsilon-caprolactone), 50:50] copolymers
      were synthesized and extruded into porous tubular scaffolds (pore size 150 +/- 50
      microm, porosity 90%) for the application to tissue engineering. The copolymers
      were basically random and amorphous. However, two T(g)'s (glass transition
      temperatures) were observed in dynamic mechanical thermal analysis and also in
      differential scanning calorimetry thermograms. Furthermore, microdomains (about
      17 nm in size) were indicated on the small-angle X-ray scattering profile and
      finally confirmed by transmission electron microscopy. Therefore, the PLCL
      copolymer was probably composed of a soft matrix of mainly epsilon-caprolactone
      moieties and hard domains containing more L-lactide units to exhibit a rubberlike
      elasticity in virtue of the physically cross-linked structure. The smooth muscle
      cells seeded scaffolds were implanted into nude mice subcutaneously for up to 15
      weeks to monitor the in vivo degradation. In addition, they were degraded in
      vitro in phosphate buffer solution (pH 7.4) for up to 1 year to compare the
      results each other. All the scaffolds degraded slowly in vivo and in vitro even
      in the form of a highly porous thin membrane. However, the degradation rate was
      somewhat faster for in vivo than for in vitro. This should be explained by
      enzymes that might have played a certain role in the degradation in the body. In
      addition, the epsilon-caprolactone moieties degraded faster than the L-lactide
      units did in these PLCL scaffolds, although their hydrophilicities are in the
      opposite order. This behavior appeared more prominently in the in vivo case. This
      should result from that the amorphous regions composed of mainly epsilon
      caprolactone units might have been first attacked by water because water can
      penetrate into the amorphous regions easier than the hard domains containing more
      L-lactides.

PMID- 15244445
TI  - Oligochitosan derivatives bearing electron-deficient aromatic rings for
      adsorption of amitriptyline: implications for drug detoxification.
AB  - The objective of this work is the synthesis of water-soluble oligochitosan
      derivatives with electron deficient aromatic rings for selective and rapid
      adsorption of amitriptyline through pi-pi complexation. Oligochitosan was
      chemically modified under homogeneous conditions in dimethyl sulfoxide (DMSO).
      (1)H NMR, FT-IR, and MALDI-TOF were employed in characterization, confirming that
      the electron deficient aromatic rings were chemically attached to the backbone of
      oligochitosan. Thromboelastography (TEG) revealed functionalized oligochitosan
      derivatives did not affect blood clotting. (1)H NMR was also utilized to observe
      the aromatic-aromatic interaction between electron deficient aromatic rings on
      oligochitosan and electron rich aromatic rings in amitriptyline. The chemical
      shift variation of aromatic protons in oligochitosan derivatives was followed to
      monitor the aromatic-aromatic interaction. Upfield shift of aromatic protons on
      benzenesulfonyl and dinitrobenzenesulfonyl groups was observed upon the addition
      of amitriptyline, supporting the formation of pi-pi complexes through aromatic
      aromatic interactions. Dinitrobenzenesulfonyl rings show a larger variation in
      chemical shift due to the presence of the electron deficient nitro groups.

PMID- 15244446
TI  - Structural processes during starch granule hydration by synchrotron radiation
      microdiffraction.
AB  - Starch granule hydration has been examined on the level of a single potato starch
      granule by static and dynamic synchrotron radiation (SR) microdiffraction
      techniques. A cryofrozen, hydrated granule was mapped through a 5 microm SR-beam
      in order to investigate its internal organization. The edge of the granule showed
      fiber texture scattering due to radially oriented amylopectin helices. The
      variation of fiber texture across the granule center supports the model of
      concentric shells. The crystalline phase appears, however, to increase strongly
      toward the granule center due to a random amylopectin fraction, which could be
      related to crystallization of short-range ordered amylopectin during hydration.
      During gelatinization, the shell structure breaks down and remaining fiber
      textured amylopectin domains belong probably to the swollen starch granule
      envelope. Hydration of a granule was initiated by a microdrop generator and
      followed in situ by SR-microdiffraction. A fast hydration process with a half
      time of about 7 s seems to reflect the porous nature of starch granules. The size
      of the hydrated domains suggests that this process is limited to the level of
      amylopectin side chain clusters. Longer hydration times are assumed to involve
      remaining short-range ordered amylopectin and results in larger domains.

PMID- 15244447
TI  - Vinyl polymers based on L-histidine residues. Part 1. The thermodynamics of
      poly(ampholyte)s in the free and in the cross-linked gel form.
AB  - Amphiphilic vinyl polymers (in the free and cross-linked forms), carrying
      carboxyl and imidazole groups, were prepared by a radical polymerization of the
      purposely synthesized N-acryloyl-L-histidine. The protonation thermodynamic
      studies (at 25 degrees C in 0.15 M NaCl) showed high polyelectrolyte character of
      the soluble polymer. Unlike the linear decreasing trend of the basicity constant,
      over the whole range of alpha (degree of protonation), the enthalpy changes for
      the protonation of the imidazole nitrogen in the polymer showed a decreasing
      pattern only at alpha > 0.5. This was ascribed to the formation of hydrogen bonds
      between protonated and free neighboring monomer units. Viscometric data revealed
      a minimum hydrodynamic volume of the polymer at its isoelectric point (pH 5),
      whereas at higher or lower pHs, the macromolecule expanded greatly as a
      consequence of the charged sites formation. This produced a preferential
      solvation of the protonated imidazole and carboxylate ions, the latter being
      surrounded by more water molecules in the hydration shell. The peculiar hydration
      behavior was confirmed in the cross-linked polymer. The hydrogel showed an
      equilibrium degree of swelling (EDS), strongly dependent on pH, in a similar
      manner as viscometric data of the soluble polymer. A linear relationship between
      the reduced viscosity and the EDS was found. The polymer was non toxic against
      the RAW264 cell line.

PMID- 15244448
TI  - Structural details of crystalline cellulose from higher plants.
AB  - It is commonly assumed that cellulose from higher plants contains the Ialpha and
      Ibeta crystalline allomorphs together with surface and disordered chains. For
      cellulose Ialpha, the evidence for its presence in higher plants is restricted to
      the C-4 signals in the solid-state (13)C NMR spectrum, which match those of
      crystalline cellulose Ialpha from algal sources. Algal cellulose Ialpha can be
      converted to the Ibeta form by high-temperature annealing. We used this approach
      to generate cellulose samples differing in Ibeta content from flax fibers and
      celery collenchyma, which respectively are representative of textile (secondary
      wall) and primary-wall cellulose. It was then possible to isolate the detailed
      spectral contributions of the surface, Ibeta and Ialpha-like phases from linear
      combinations of the observed (13)C NMR and FTIR spectra. The (13)C NMR spectra
      resembled those of highly crystalline tunicate or algal cellulose Ibeta and
      Ialpha, with slight differences implying increased disorder and minor
      conformational discrepancies. The FTIR spectrum of the Ibeta form was closely
      similar to its more crystalline counterparts, but the FTIR spectrum of the Ialpha
      form was not. In addition to increased bandwith indicative of lower order, it
      showed substantial differences in the profile of hydroxyl stretching bands. These
      results confirm that higher plants synthesize cellulose Ibeta but show that the
      Ialpha-like chains, although conformationally quite similar to crystalline algal
      cellulose Ialpha, sit in a different hydrogen-bonding environment in higher
      plants. The differences are presumably occasioned by the small diameter of the
      crystallites and the influence of the crystallite surface on chain packing.

PMID- 15244449
TI  - In vitro reconstitution of fibrillar collagen type I assemblies at reactive
      polymer surfaces.
AB  - The reconstitution of fibrillar collagen and its assemblies with heparin and
      hyaluronic acid was studied in vitro. Fibril formation kinetics were analyzed by
      turbidity and depletion measurements in solutions containing varied
      concentrations of collagen and glycosaminoglycans. Fibril-forming collagen
      solutions were further applied for the coating of planar substrates which had
      been modified with alternating maleic anhydride copolymer films before. The
      immobilized collagen assemblies were characterized with respect to the deposited
      amount of protein using ellipsometry and acidic hydrolysis/HPLC-based amino acid
      analysis, respectively. AFM, SEM, and cLSM were utilized to gain information on
      structural features and patterns formed by surface-attached fibrils depending on
      the initial solution concentrations of collagen. The results revealed that the
      addition of heparin and hyaluronic acid affected both the fibril dimensions and
      the meshwork characteristics of the surface-bound fibrils.

PMID- 15244450
TI  - Giant bent-core mesogens in the thread forming process of marine mussels.
AB  - In marine mussels (Mytilus), byssal threads are made in minutes from
      prefabricated smectic polymer liquid crystals by a process resembling reaction
      injection molding. The mesogens in these arrays are known to be natural block
      copolymers with rodlike collagen cores. Using atomic force microscopy, it was
      shown that these collagenous mesogens are bent-core or banana-shaped in a manner
      that is consistent with and predictable from their amino acid sequence. The
      overall bend angle in preCOL-NG in Mytilus galloprovincialis is about 130
      degrees. The mesogens have a center-to-center separation of approximately 22 nm
      and a length of 200 nm. It is evident that the smectic structure of the
      prefabricated mesophases remains largely intact over 1-3 microm distances in the
      molded fibers and is presumably locked in place during molding by cross-linking.
      Like the smectic liquid crystals of many synthetic banana mesogens, the
      collagenous mesogens of the byssal threads exhibit SmC(2) symmetry with a
      characteristic tilt of 24.6 degrees. At about 100% extension, this tilt is
      considerably reduced and the globular end domains are no longer visible
      presumably because they have been unraveled.

PMID- 15244451
TI  - Zein adsorption to hydrophilic and hydrophobic surfaces investigated by surface
      plasmon resonance.
AB  - Zein, the prolamine of corn, has been investigated for its potential as an
      industrial biopolymer. In previous research, zein was plasticized with oleic acid
      and formed into sheets/films. Physical properties of films were affected by film
      structure and controlled in turn by zein-oleic acid interactions. The nature of
      such interactions is not well understood. Thus, protein-fatty acid interactions
      were investigated in this work by the use of surface plasmon resonance (SPR).
      Zein adsorption from 75% aqueous 2-propanol solutions, 0.05% to 0.5% w/v, onto
      hydrophilic and hydrophobic self-assembled monolayers (SAMs) formed by 11
      mercaptoundecanoic acid and 1-octanethiol, respectively, was monitored by high
      time resolution SPR. Initial adsorption rate and ultimate surface coverage
      increased with bulk protein concentration for both surfaces. The initial slope of
      plotted adsorption isotherms was higher on 11-mercaptoundecanoic acid than on 1
      octanethiol, indicating higher zein affinity for hydrophilic SAMs. Also, maximum
      adsorption values were higher for zein on hydrophilic than on hydrophobic SAMs.
      Flushing off loosely bound zein in the SPR cell allowed estimation of apparent
      monolayer values. Differences in monolayer values for hydrophobic and hydrophilic
      surfaces were explained in terms of zein adsorption footprint.

PMID- 15244452
TI  - Guanidine hydrochloride can induce amyloid fibril formation from hen egg-white
      lysozyme.
AB  - The formation of amyloid fibrils is an intractable problem in which normally
      soluble protein polymerizes and forms insoluble ordered aggregates. Such
      aggregates can range from being a nuisance in vitro to being toxic in vivo. The
      latter is true for lysozyme, which has been shown to form toxic deposits in
      humans. In the present study, the effects of partial denaturation of hen egg
      white lysozyme via incubation in a concentrated solution of the denaturant
      guanidine hydrochloride are investigated. Results show that when lysozyme is
      incubated under moderate guanidine hydrochloride concentrations (i.e., 2-5 M),
      where lysozyme is partially unfolded, fibrils form rapidly. Thioflavin T, Congo
      red, X-ray diffraction, transmission electron microscopy, atomic force
      microscopy, and circular dichroism spectroscopy are all used to verify the
      production of fibrils under these conditions. Incubation at very low or very high
      guanidine hydrochloride concentrations fails to produce fibrils. At very low
      denaturant concentrations, the structure of lysozyme is fully native and very
      stable. On the other hand, at very high denaturant concentrations, guanidine
      hydrochloride is capable of dissolving and dis-aggregating fibrils that are
      formed. Raising the temperature and/or concentration of lysozyme accelerates
      fibril formation by further adding to the concentration of partially unfolded
      species. The addition of preformed fibrils also accelerates fibril formation but
      only under partially unfolding conditions. The results presented here provide
      further evidence that partial unfolding is a prerequisite to fibril formation.
      Partial denaturation can accelerate fibril formation in much the same way that
      mutations have been shown to accelerate fibril formation.

PMID- 15244453
TI  - Polyamidoamine (Yet Not PAMAM) dendrimers as bioinspired materials for drug
      delivery: structure-activity relationships by molecular simulations.
AB  - In this paper, we report the results obtained from a comprehensive
      characterization of newly synthesized dendrimeric molecules in a solvated
      environment, by computer-aided simulations. The evidences allowed us to formulate
      some structure-activity relationships (SARs) between the experimentally verified
      cytotoxicity/noncytotoxicity of these compounds and some molecular features such
      as, for instance, radius of gyration, molecular shape, and dimensions. In
      particular, all noncytotoxic dendrimers were characterized by a more dense and
      globular shape and by a smoother surface pattern, as quantified by their fractal
      dimension D.

PMID- 15244454
TI  - Production of bioactive cellulose films reconstituted from ionic liquids.
AB  - A new method for introducing enzymes into cellulosic matrixes which can be formed
      into membranes, films, or beads has been developed using a cellulose-in-ionic
      liquid dissolution and regeneration process. Initial results on the formation of
      thin cellulose films incorporating dispersed laccase indicate that active enzyme
      encapsulated films can be prepared using this methodology and that precoating the
      enzyme with a second, hydrophobic ionic liquid prior to dispersion in the
      cellulose/ionic liquid solution can provide an increase in enzyme activity
      relative to that of untreated films, presumably by providing a stabilizing
      microenvironment for the enzyme.

PMID- 15244455
TI  - Polymorphism of cellulose I family: reinvestigation of cellulose IVI.
AB  - Polymorphs of cellulose I, III(I), and IV(I) have been investigated by X-ray
      diffraction, FT-IR, and solid-state (13)C NMR spectroscopy. Highly crystalline
      cellulose III(I) samples were prepared by treating cellulose samples in
      supercritical ammonia at 140 degrees C for 1 h, and conventional cellulose III(I)
      samples were prepared by liquid ammonia treatment. The cellulose IV(I) sample of
      highest crystallinity was that prepared from Cladophora cellulose III(I) in
      supercritical ammonia, followed by the sample treated in glycerol at 260 degrees
      C for 0.5 h, whereas the lowest crystallinity was observed in ramie cellulose
      prepared by conventional liquid ammonia treatment followed by glycerol annealing.
      In general, the perfection of cellulose IV(I) depends on the crystallinity of the
      original material: either of the starting cellulose I or of the cellulose III(I)
      after ammonia treatment. The product thus obtained was analogous to cellulose
      I(beta), which is what it should be called rather than cellulose IV(I). If the
      existence of the polymorph cellulose IV(I) is not accepted, the observations on
      which it has been based may be explained by the fact that the structure termed
      cellulose IV(I) is cellulose I(beta) which contains lateral disorder.

PMID- 15244456
TI  - Chemical modification of silk sericin in lithium chloride/dimethyl sulfoxide
      solvent with 4-cyanophenyl isocyanate.
AB  - This paper reports chemical modification of silk sericin in LiCl/dimethyl
      sulfoxide (DMSO) solvent with 4-cyanophenyl isocyanate. Sericin is a highly
      hydrophilic protein secreted by Bombyx mori, serving as a protein glue in a
      cocoon. LiCl/DMSO was found to be a good solvent of sericin and useful for
      homogeneous modification of its abundant hydroxyl groups under nonaqueous
      condition. Fourier transform infrared (FTIR) analysis of the modified sericins
      revealed that 4-cyanophenyl groups were incorporated into sericin molecules
      mainly through urethane linkages. Several characteristics of the modified
      sericins such as solubility characteristic, hygroscopic property, and thermal
      stability were investigated. Secondary structure analysis using FTIR spectra
      suggested that formation of strong intermolecular hydrogen bonds was inhibited by
      the modification that is probably attributable to the incorporation of bulky 4
      cyanophenyl groups. These results demonstrate that chemical modification of
      sericin using LiCl/DMSO solvent markedly alters its characteristics.

PMID- 15244457
TI  - Synthesis and characterization of thermoset biodegradable elastomers based on
      star-poly(epsilon-caprolactone-co-D,L-lactide).
AB  - Biodegradable elastomers represent a useful class of biomaterials. In this paper,
      we synthesize thermoset elastomers by utilizing the living nature of ring-opening
      polymerization of a star copolymer of D,L-lactide and epsilon-caprolactone
      initiated with glycerol and catalyzed by stannous 2-ethylhexanoate. The star
      copolymers were synthesized of varying molecular weight and monomer composition
      and cross-linked by compression molding using a dilactone, bis(epsilon
      caprolactone-4-yl)propane dissolved in epsilon-caprolactone monomer. The
      elastomers were then characterized by differential scanning calorimetry and
      uniaxial tensile testing and their physical properties related to the nature of
      the star copolymer prepolymers. The results demonstrate a means of predictably
      altering the elastomer physical properties by adjusting the star copolymer
      prepolymer initial molecular weight and monomer ratio.

PMID- 15244458
TI  - NMR imaging of the diffusion of water at 310 K into semi-IPNs of PEM and
      poly(HEMA-co-THFMA) with and without chlorhexidine diacetate.
AB  - Magnetic resonance imaging has been used to monitor the diffusion of water at 310
      K into a series of semi-IPNs of poly(ethyl methacrylate), PEM, and copolymers of
      2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA.
      The diffusion was found to be well described by a Fickian kinetic model in the
      early stages of the water sorption process, and the diffusion coefficients were
      found to be slightly smaller than those for the copolymers of HEMA and THFMA,
      P(HEMA-co-THFMA), containing the same mole fraction of HEMA in the matrix. A
      second stage sorption process was identified in the later stage of water sorption
      by the PEM/PTHFMA semi-IPN and for the systems containing a P(HEMA-co-THFMA)
      component with a mole fraction HEMA of 0.6 or less. This was characterized by the
      presence of water near the surface of the cylinders with a longer NMR T(2)
      relaxation time, which would be characteristic of mobile water, such as water
      present in large pores or surface fissures. The presence of the drug
      chlorhexidine in the polymer matrixes at a concentration of 5.625 wt % was found
      not to modify the properties significantly, but the diffusion coefficients for
      the water sorption were systematically smaller when the drug was present.

PMID- 15244459
TI  - Novel thymine-functionalized polystyrenes for applications in biotechnology. 2.
      Adsorption of model proteins.
AB  - This paper investigates the adsorption of bovine serum albumin (BSA) and bovine
      hemoglobin (BHb) model proteins onto novel thymine-functionalized polystyrene (PS
      VBT) microspheres, in comparison with polystyrene (PS) microspheres. Maximum
      adsorption was obtained for both proteins near their corresponding isoelectric
      points (pI at pH = 4.7 for BSA and 7.1 for BHb). FTIR and adsorption isotherm
      analysis demonstrated that, although both proteins were physisorbed onto PS
      through nonspecific hydrophobic interactions, adsorption onto the functionalized
      copolymers occurred by both physisorption and chemisorption via hydrogen bonding.
      FTIR analysis also indicated conformational changes in the secondary structure of
      BSA and BHb adsorbed onto PS, whereas little or no conformation change was seen
      in the case of adsorption onto PS-VBT. Atomic force microscopy (AFM), consistent
      with the isotherm results, also demonstrated monolayer adsorption for both
      proteins. AFM images of BSA adsorbed onto copolymers with 20 mol % surface VBT
      loading showed exclusively end-on orientation. Adsorption onto copolymers with
      lower functionality showed mixed end-on and side-on orientation modes of BSA, and
      only the side-on orientation was observed on PS. The AFM results agreed well with
      theoretically calculated and experimentally obtained adsorption capacities. AFM
      together with calculated and observed adsorption capacity data for BHb indicated
      that this protein might be highly compressed on the copolymer surface. Adsorption
      from a binary mixture of BSA and BHb onto PS-VBT showed good separation at
      pH=7.0; approximately 90% of the adsorbed protein was BHb. The novel copolymers
      have potential applications in biotechnology.

PMID- 15244460
TI  - Understanding the mechanism of action of poly(amidoamine)s as endosomolytic
      polymers: correlation of physicochemical and biological properties.
AB  - Bioresponsive poly(amidoamine)s (PAA)s are currently under development as
      endosomolytic polymers for intracellular delivery of proteins and genes. Here for
      the first time, small-angle neutron scattering (SANS) is used to systematically
      investigate the pH-dependent conformational change of an endosomolytic polymer,
      the PAA ISA 23. The radius of gyration of the ISA23 was determined as a function
      of pH and counterion, the aim being to correlate changes in polymer conformation
      with membrane activity assessed using a rat red blood cell haemolysis assay. With
      decreasing pH, the ISA23 radius of gyration increased to a maximum (R(g)
      approximately 80 A) around pH = 3, before subsequently decreasing once more. At
      high pH and therefore high ionic strengths, the polymer is negatively charged and
      adopts a rather compact structure (R(g) approximately 20 A), presumably with the
      dissociated carboxylic groups on the exterior of the polymer coil. At low pH, the
      coil again collapses (R(g) < 20 A), presumably due to the effects of the high
      ionic strength. It is concluded that the nature of the salt form has no direct
      bearing on the size of the polymer coil, but it does indirectly determine the
      prevailing pH and, hence, polymer conformation. Pulsed-gradient spin-echo NMR
      measurements were in good agreement with the SANS estimates of the radius of
      gyration, although ISA23 polydispersity does complicate the data
      interpretation/comparison. These results support the proposed mode of action of
      PAAs, namely a coil expansion on passing from a neutral pH (extracellular) to an
      acidic pH (endosomal and lysosomal) environments. The results do, however,
      suggest that the charge on the polymer shows a closer correlation with the
      haemolysis activity rather than the polymer conformation.

PMID- 15244461
TI  - Electro-spinning and electro-blowing of hyaluronic acid.
AB  - In this study, hyaluronic acid (HA) was electro-spun and electro-blown to prepare
      nonwoven nanofibrous membranes. Critical parameters for processing and
      corresponding effects on the membrane morphology were investigated using the
      methods of rheology and scanning electron microscopy (SEM). During electro
      spinning, the optimal HA concentration window for nanofibrous formation was
      determined within a narrow range of 1.3-1.5 w/v %, corresponding to a solution
      viscosity range of 3-30 Pa s at a shear rate of 1 s(-1). SEM results indicated
      that, with increases in (1) the total concentration by blending of low molecular
      weight HA, (2) the evaporation rate by the addition of ethanol, and/or (3) the
      feeding rate of solution, the electro-spinning performance for creating
      nanofibers was improved. However, the improvement was not sufficient to achieve a
      consistent production of high quality nonwoven nanofiber membranes. This problem
      was overcome by a new electro-blowing process using the combination of air flow
      and electro-spinning. Although air blowing at room temperature around the
      spinneret orifice did not exhibit a remarkable enhancement of nanofiber formation
      of HA, the performance was significantly improved with an increase in the air
      blowing rate. SEM results showed that the temperature of air-blowing was the most
      effective parameter in ensuring HA nanofiber formation. As the temperature of the
      blown air increased from 25 to 57 degrees C, the nanofiber formation became
      consistent and uniform. A high quality HA nonwoven membrane of nanofibers was
      successfully produced by blowing air at 57 degrees C with a 70 ft(3)/hr flow
      rate.

PMID- 15244462
TI  - Composition and structure of whey protein/gum arabic coacervates.
AB  - Complex coacervation in whey protein/gum arabic (WP/GA) mixtures was studied as a
      function of three main key parameters: pH, initial protein to polysaccharide
      mixing ratio (Pr:Ps)(ini), and ionic strength. Previous studies had already
      revealed under which conditions a coacervate phase was obtained. This study is
      aimed at understanding how these parameters influence the phase separation
      kinetics, the coacervate composition, and the internal coacervate structure. At a
      defined (Pr:Ps)(ini), an optimum pH of complex coacervation was found (pH(opt)),
      at which the strength of electrostatic interaction was maximum. For (Pr:Ps)(ini)
      = 2:1, the phase separation occurred the fastest and the final coacervate volume
      was the largest at pH(opt) = 4.0. The composition of the coacervate phase was
      determined after 48 h of phase separation and revealed that, at pH(opt), the
      coacervate phase was the most concentrated. Varying the (Pr:Ps)(ini) shifted the
      pH(opt) to higher values when (Pr:Ps)(ini) was increased and to lower values when
      (Pr:Ps)(ini) was decreased. This phenomenon was due to the level of charge
      compensation of the WP/GA complexes. Finally, the structure of the coacervate
      phase was studied with small-angle X-ray scattering (SAXS). SAXS data confirmed
      that at pH(opt) the coacervate phase was dense and structured. Model calculations
      revealed that the structure factor of WP induced a peak at Q = 0.7 nm(-1),
      illustrating that the coacervate phase was more structured, inducing the stronger
      correlation length of WP molecules. When the pH was changed to more acidic
      values, the correlation peak faded away, due to a more open structure of the
      coacervate. A shoulder in the scattering pattern of the coacervates was visible
      at small Q. This peak was attributed to the presence of residual charges on the
      GA. The peak intensity was reduced when the strength of interaction was
      increased, highlighting a greater charge compensation of the polyelectrolyte.
      Finally, increasing the ionic strength led to a less concentrated, a more
      heterogeneous, and a less structured coacervate phase, induced by the screening
      of the electrostatic interactions.

PMID- 15244463
TI  - Mechanical properties of poly(lactic acid)/starch composites compatibilized by
      maleic anhydride.
AB  - Blending poly(lactic acid) (PLA) with wheat starch compatibized by maleic
      anhydride (MA) was performed with a lab-scale co-extruder. An initiator, 2,5
      bis(tert-butylperoxy)-2,5 dimethylhexane (L101), was used to improve
      compatability among PLA, starch and MA. Interfacial adhesion between PLA and
      starch was significantly improved. Mechanical properties increased markedly
      compared to the virgin composites of PLA/starch. The PLA/starch composites at a
      constant ratio of 55/45 compatibilized by 1% MA and initiated by 10% L101 (MA
      basis) resulted in the highest tensile strength and elongation.

PMID- 15244464
TI  - Toward non-toxic antifouling: synthesis of hydroxy-, cinnamic acid-, sulfate-,
      and zosteric acid-labeled poly[3-hydroxyalkanoates].
AB  - The side-chain double bonds of bacterial poly[3-hydroxyalkanoate-co-3
      hydroxyalkenoate] (PHAE, 1) were transformed into thioether bonds (derivative 2)
      via the radical addition reaction of 11-mercapto-1-undecanol. The terminal
      hydroxy functionalities of derivative 2 were subsequently esterified with
      cinnamic acid (derivative 3), sulfatized with ClSO(3)H (derivative 4), or coupled
      with tert-butyldimethylsilyl-protected coumaric acid, to give, after deprotection
      with tetrabutylammonium fluoride (derivative 5) followed by sulfatization, p
      (sulfooxy) cinnamic acid- (zosteric acid) labeled PHAE (derivative 6). The
      reactions proceeded with good yields and little side reactions, which was
      confirmed with (1)H NMR and GPC experiments. These functionalized polyesters are
      currently investigated as environmentally friendly coatings to protect surfaces
      from biofouling.

PMID- 15244465
TI  - Effective enhancement of short-chain-length-medium-chain-length
      polyhydroxyalkanoate copolymer production by coexpression of genetically
      engineered 3-ketoacyl-acyl-carrier-protein synthase III (fabH) and
      polyhydroxyalkanoate synthesis genes.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that have a wide
      variety of physical properties dependent on the lengths of the pendant groups of
      the monomer units in the polymer. PHAs composed of mostly short-chain-length
      (SCL) monomers are often stiff and brittle, whereas PHAs composed of mostly
      medium-chain-length (MCL) monomers are elastomeric in nature. SCL-MCL PHA
      copolymers can have properties between the two states, dependent on the ratio of
      SCL and MCL monomers in the copolymer. It is desirable to elucidate new and low
      cost ways to produce PHA composed of mostly SCL monomer units with a small mol %
      of MCL monomers from renewable resources, since this type of SCL-MCL PHA
      copolymer has superior qualities compared to SCL homopolymer. To address this
      issue, we have created strains of recombinant E. coli capable of producing beta
      ketothiolase (PhbA) and acetoacetyl-CoA synthase (PhbB) from Ralstonia eutropha,
      genetically engineered 3-ketoacyl-ACP synthase III (FabH) from Escherichia coli,
      and genetically engineered PHA synthases (PhaC) from Pseudomonas sp. 61-3 to
      enhance the production of SCL-MCL PHA copolymers from glucose. The cumulative
      effect of having two monomer-supplying pathways and genetically engineered PHA
      synthases resulted in higher accumulated amounts of SCL-MCL PHA copolymer from
      glucose. Polymers were isolated from two recombinant E. coli strains, the first
      harboring the phbAB, fabH(F87T), and phaC1(SCQM) genes and the second harboring
      the phbAB, fabH(F87W), and phaC1(SCQM) genes. The thermal and physical properties
      of the isolated polymers were characterized. It was found that even a very low
      mol % of MCL monomer in a SCL-MCL PHA copolymer had dramatic effects on the
      thermal properties of the copolymers.

PMID- 15244466
TI  - 20S proteasome prevents aggregation of heat-denatured proteins without PA700
      regulatory subcomplex like a molecular chaperone.
AB  - The eukaryotic 20S proteasome is the multifunctional catalytic core of the 26S
      proteasome, which plays a central role in intracellular protein degradation.
      Association of the 20S core with a regulatory subcomplex, termed PA700 (also
      known as the 19S cap), forms the 26S proteasome, which degrades ubiquitinated and
      nonubiquitinated proteins through an ATP-dependent process. Although proteolytic
      assistance by this regulatory particle is a general feature of proteasome
      dependent turnover, the 20S proteasome itself can degrade some proteins directly,
      bypassing ubiquitination and PA700, as an alternative mechanism in vitro. The
      mechanism underlying this pathway is based on the ability of the 20S proteasome
      to recognize partially unfolded proteins. Here we show that the 20S proteasome
      recognizes the heat-denatured forms of model proteins such as citrate synthase,
      malate dehydrogenase. and glyceraldehydes-3-phosphate dehydrogenase, and prevents
      their aggregation in vitro. This process was not followed by the refolding of
      these denatured substrates into their native states, whereas PA700 or the 26S
      proteasome generally promotes their reactivation. These results indicate that the
      20S proteasome might play a role in maintaining denatured and misfolded
      substrates in a soluble state, thereby facilitating their refolding or
      degradation.

PMID- 15244467
TI  - Rheological and structural properties of aqueous alginate during gelation via the
      Ugi multicomponent condensation reaction.
AB  - Turbidity, structure, and rheological features during gelation via the Ugi
      multicomponent condensation reaction of semidilute solutions of alginate have
      been investigated at different polymer and cross-linker concentrations and
      reaction temperatures. The gelation time of the system decreased with increasing
      polymer and cross-linker concentrations, and a temperature rise resulted in a
      faster gelation. At the gel point, a power law frequency dependence of the
      dynamic storage modulus (G' proportional, variant omega(n)(')) and loss modulus
      (G' ' proportional, variant omega(n)(' ')) was observed for all gelling systems
      with n' = n' ' = n. By varying the cross-linker density at a fixed polymer
      concentration (2.2 wt %), the power law exponent is consistent with that
      predicted (0.7) from the percolation model. The value of n decreases with
      increasing polymer concentration, whereas higher temperatures give rise to higher
      values of n. The elastic properties of the gels continue to grow over a long time
      in the postgel region, and at later stages in the gelation process, a solidlike
      response is observed. The turbidity of the gelling system increases as the gel
      evolves, and this effect is more pronounced at higher cross-linker concentration.
      The small-angle neutron scattering results reveal large-scale inhomogeneities of
      the gels, and this effect is enhanced as the cross-linker density increases. The
      structural, turbidity, and rheological features were found to change over an
      extended time after the formation of the incipient gel. It was demonstrated that
      temperature, polymer, and cross-linker concentrations could be utilized to tune
      the physical properties of the Ugi gels such as structure, transparency, and
      viscoelasticity.

PMID- 15244468
TI  - Effects of residual zinc compounds and chain-end structure on thermal degradation
      of poly(epsilon-caprolactone).
AB  - Effects of chain-end structure and residual metal compounds on thermal
      degradation of poly(epsilon-caprolactone) (PCL) were investigated by means of
      thermogravimetric and pyrolysis-gas chromatograph mass spectrometric analyses.
      Four types of PCL samples with different chain-end structures (alpha-carboxylic
      acid-omega-hydroxyl-PCL, alpha-dodecyl ester-omega-hydroxyl-PCL, alpha-carboxylic
      acid-omega-acetyl-PCL, and alpha-dodecyl ester-omega-acetyl-PCL) were prepared by
      ring-opening polymerization of epsilon-caprolactone in the presence of zinc-based
      catalyst and by subsequent acetylation reaction of polymers with acetic
      anhydride. PCL samples with different zinc contents were obtained by washing with
      acetic acid in chloroform solution of polymer. Thermal degradation behaviors of
      these PCL samples with different chain-end structures were examined under both
      isothermal and nonisothermal conditions. From both the isothermal and
      nonisothermal experiments, the thermal degradation of PCL samples containing high
      amounts of residual zinc compounds from synthesis process revealed the selective
      unzipping depolymerization step below 300 degrees C producing epsilon
      caprolactone exclusively. In contrast, zinc-free PCL samples were stable at
      temperatures below 300 degrees C, and the thermal degradation occurred only at
      temperatures above 300 degrees C regardless of the chain-end structure. From (1)H
      NMR analysis of the residual molecules after isothermal degradation of zinc-free
      PCL, it was confirmed that the omega-chain-end of residual molecules was 5
      hexenoic acid unit. However, the cyclic monomer and oligomers were detected as
      the volatile products of zinc-free PCL samples. These results suggest that the
      dominant reaction of thermal degradation for PCL above 300 degrees C is a
      competition between the random chain scission via cis elimination reaction and
      the cyclic rupture via intramolecular transesterification of PCL molecules.

PMID- 15244469
TI  - Preparation and in vitro evaluation of primaquine-conjugated gum arabic
      microspheres.
AB  - Gum arabic, a branched polysaccharide, was oxidized using periodate to generate
      reactive aldehyde groups on the biopolymer. Primaquine, an 8-aminoquinoline, was
      covalently coupled onto oxidized gum arabic via an imine bond and simultaneously
      fabricated into microspheres of less than 2 microm in size by heat denaturation
      in a reverse emulsion of 1:1 light paraffin oil and toluene stabilized by
      sorbitan sesquioleate as the surfactant. The covalent binding of primaquine to
      the polysaccharide using the clinically used water-soluble form of the drug
      primaquine phosphate was achieved in the presence of borate buffer of pH 11. Up
      to 35% of the drug could be bound to the polymer backbone depending on the
      concentration of the drug employed initially and the degree of oxidation of the
      polysaccharide. Interestingly, both the aliphatic and the hindered aromatic amino
      groups of primaquine were found to react with the aldehyde functions through
      Schiff base formation leading to cross-linking of the polysaccharide with the
      drug itself. In vitro release of the drug from microspheres into phosphate
      buffered saline (PBS, pH 7.4, 0.1 M) at 37 degrees C showed that the release of
      primaquine from the matrix was slow, although gradually increased with time. The
      maximum released was below 50% of the drug payload even after 10 days. Release
      into simulated gastric and intestinal fluids was faster compared to the release
      in PBS due to rapid hydrolysis of the Schiff's linkage in the gastric fluid. A
      possible reason for the poor hydrolytic susceptibility of the Schiff's linkage is
      suggested based on the unequal reactivity of the amino groups on primaquine and
      its relevance in possible therapeutic application of this polymer-drug conjugate
      discussed.

PMID- 15244470
TI  - Characterization of surface-immobilized layers of intact liposomes.
AB  - Surface-immobilized liposome layers are of interest for various potential
      applications such as localized drug delivery, but their characterization is
      challenging. We have employed an AFM method and fluorescent dye release to
      analyze anchored liposomes. In addition, we studied whether the liposomes are
      surface-bound solely via specific interaction (NeutrAvidin/biotin) or whether
      physisorptive binding also plays a role. Liposomes containing PEG-biotin lipids
      were affinity bound to NeutrAvidin molecules which had been immobilized onto
      solid supports via three different hydrogel interlayers. After liposome docking,
      approaching the surface with a colloid probe mounted onto an AFM cantilever
      showed considerable compression behavior, consistent with expectation based on
      intact, deformable liposomes but not lipid bilayers, thus showing that disruption
      of liposomes did not occur upon immobilization onto these support surfaces.
      Plastic deformation suggestive of liposome disruption on compression was not
      observed. The kinetics of fluorescent dye release also demonstrated that intact
      liposomes had been successfully immobilized onto all three supports. Blocking
      surface-immobilized NeutrAvidin molecules with excess biotin in solution before
      exposure to liposomes showed that the docking of liposomes was dependent largely
      but not exclusively on biotin-NeutrAvidin affinity binding, with evidence for
      some nonspecific physisorption, as the extent of liposome binding onto blocked
      NeutrAvidin surfaces was appreciably lower than for unblocked surfaces but not
      zero. Finally, consecutive addition of further NeutrAvidin and liposome layers
      enabled fabrication of multilayers, and this was clearly seen in AFM
      compressibility and fluorescent dye release measurements.

PMID- 15244471
TI  - Gliadins polymerized with cysteine: effects on the physical and water barrier
      properties of derived films.
AB  - To study the effects of disulfide bonds on certain functional properties of films
      made from the wheat gluten proteins gliadin and glutenin, cysteine was used to
      promote the formation of interchain disulfide bridges between gliadins in 70%
      ethanolic solution. Disulfide-mediated polymerization of gliadins was confirmed
      by means of SDS-PAGE analysis. After chemical treatment of gliadins, films were
      solution cast and the effects of both glycerol (used as a plasticizer) and
      relative humidity were studied on water vapor permeability, moisture sorption
      isotherms at 23 degrees C, and the optical properties of the films. The results
      were compared with those obtained from analogous films made from untreated
      glutenin macromolecules. Cysteine-mediated polymerization of gliadins improved
      the water vapor resistance of films achieving values close to those obtained for
      glutenin films. Development of intra- and interchain disulfide bonds did not
      change the moisture sorption capacity of the films but transparency was slightly
      diminished.

PMID- 15244472
TI  - AFM study of the elastin-like biopolymer poly(ValGlyGlyValGly).
AB  - In this paper, we report an AFM study on the supramolecular structures adopted by
      the synthetic polypentapeptide poly(ValGlyGlyValGly), whose monomeric sequence is
      an abundant, simple building block of elastin. The polypeptide was analyzed by
      deposition from both methanolic and aqueous suspensions, showing different
      behaviors. In methanol, the polypeptide is able to evolve, in a time-dependent
      way, from layers to ribbons to beaded filaments. When the equilibrium is reached,
      the formation of well-defined dendritic structures is also observed. This
      restructuring of the polypentapeptide seems to be reminiscent of a sort of
      Rayleigh instability. When deposited from aqueous suspensions, the polypeptide
      self-assembles either in fibrillar networks or in amyloid-like patterns, both of
      them being found in elastin or elastin-related polypeptides. As a general
      finding, poly(ValGlyGlyValGly) seems to constitute an excellent mimetic of the
      supramolecular properties of native elastin.

PMID- 15244473
TI  - Atomic force microscopy of pea starch: origins of image contrast.
AB  - Atomic force microscopy (AFM) has been used to image the internal structure of
      pea starch granules. Starch granules were encased in a nonpenetrating matrix of
      rapid-set Araldite. Images were obtained of the internal structure of starch
      exposed by cutting the face of the block and of starch in sections collected on
      water. These images have been obtained without staining, or either chemical or
      enzymatic treatment of the granule. It has been demonstrated that contrast in the
      AFM images is due to localized absorption of water within specific regions of the
      exposed fragments of the starch granules. These regions swell, becoming "softer"
      and higher than surrounding regions. The images obtained confirm the "blocklet
      model" of starch granule architecture. By using topographic, error signal and
      force modulation imaging modes on samples of the wild-type pea starch and the
      high amylose r near-isogenic mutant, it has been possible to demonstrate
      differing structures within granules of different origin. These architectural
      changes provide a basis for explaining the changed appearance and functionality
      of the r mutant. The growth-ring structure of the granule is suggested to arise
      from localized "defects" in blocklet distribution within the granule. It is
      proposed that these defects are partially crystalline regions devoid of amylose.

PMID- 15244474
TI  - Material properties of plasticized hardwood xylans for potential application as
      oxygen barrier films.
AB  - Free films based on glucuronoxylan isolated from aspen wood were prepared by
      casting from aqueous solutions and drying in a controlled environment. Addition
      of xylitol or sorbitol facilitated film formation and thus examination of the
      material properties of these films. The mechanical properties of the films were
      evaluated using tensile testing and dynamic mechanical analysis in a controlled
      ambient relative humidity. The strain at break increased, and the stress at break
      and Young's modulus of the films decreased with increasing amounts of xylitol and
      sorbitol due to plasticization. At high amount of plasticizer, it was found that
      films with xylitol gave lower extensibility. Wide-angle X-ray scattering analysis
      showed that xylitol crystallized in a distinct phase, which we believe
      contributes to the more brittle behavior of these films. The effect of the
      plasticizers on the glass transition temperature was determined using dynamic
      mechanical analysis and differential scanning calorimetry. An increased amount of
      plasticizer shifted the glass transition to lower temperatures. The effect of
      moisture on the properties of plasticized films was investigated using water
      vapor sorption isotherms and by humidity scans in dynamic mechanical analysis.
      Sorption isotherms showed a transition from type II to type III when adding
      plasticizer. The films showed low oxygen permeability and thus have a potential
      application in food packaging.

PMID- 15244475
TI  - Structure and dynamics of flour by solid state NMR: effects of hydration and
      wheat aging.
AB  - The effects of accelerated aging of wheat seeds on structural and dynamic
      properties of dry and hydrated (ca 10 wt % H(2)O) flour at a molecular level were
      investigated by several high and low resolution solid-state NMR techniques.
      Identification and characterization of domains with different mobility was
      performed by (13)C direct excitation (DE) and cross-polarization (CP) magic angle
      spinning (MAS), as well as by (1)H static and MAS experiments. (1)H spin-lattice
      relaxation times (T(1) and T(1)(rho)) measurements were carried out to
      investigate molecular motions in different frequency ranges. Experimental data
      show that the main components of flour (starch and gluten proteins) are in a
      glassy phase, whereas the mobile fraction is constituted by lipids and, in
      hydrated samples, absorbed water. A lower proportion of rigid domains, as well as
      an increased dynamics of all flour components are observed after both seeds aging
      and flour hydration. Linear average dimensions between 20 and 200 A are estimated
      for water domains in hydrated samples.

PMID- 15244476
TI  - Optimization of the preparation of aqueous suspensions of waxy maize starch
      nanocrystals using a response surface methodology.
AB  - Response surface methodology was used to investigate the effect of five selected
      factors on the selective H(2)SO(4) hydrolysis of waxy maize starch granules.
      These predictors were temperature, acid concentration, starch concentration,
      hydrolysis duration, and stirring speed. The goal of this study was to optimize
      the preparation of aqueous suspensions of starch nanocrystals, i.e., to determine
      the operative conditions leading to the smallest size of insoluble hydrolyzed
      residue within the shortest time and with the highest yield. Therefore empirical
      models were elaborated for the hydrolysis yield and the size of the insoluble
      residues using a central composite face design involving 31 trials. They allowed
      us to show that it was possible to obtain starch nanocrystals after only 5 days
      of H(2)SO(4) hydrolysis with a yield of 15 wt % and having the same shape as
      those obtained from the classical procedure after 40 days of HCl treatment, with
      a yield of 0.5 wt %.

PMID- 15244477
TI  - Binding of Mg2+, Cd2+, and Ni2+ to liquid crystalline NaDNA: polarized light
      microscopy and NMR investigations.
AB  - The interaction of the divalent metal ions Mg(2+), Cd(2+), and Ni(2+) with liquid
      crystalline NaDNA solutions (molar ratios Me(2+)/DNA-phosphate </=0.050) was
      investigated by polarized light microscopy and multinuclear (31)P, (2)H, and
      (23)Na NMR. Our findings show that the state of the cholesteric NaDNA phase at
      equal MgCl(2), CdCl(2), or NiCl(2) concentration is affected in a different way
      and to a different extent by the nature of the divalent cation. Indeed, we found
      that the occurrence of an isotropic phase is markedly favored by Mg(2+), and to a
      lower extent by Cd(2+), and that the pitch of the cholesteric phase decreases in
      the presence of Cd(2+) or Ni(2+). (23)Na NMR spectroscopy also shows differences
      between the binding behavior of Mg(2+) and the transition metal ions in the
      counterion atmosphere around DNA. The results are discussed in terms of different
      binding modes of the metal ions.

PMID- 15244478
TI  - Uniaxial drawing and mechanical properties of poly[(R)-3-hydroxybutyrate]/poly(L
      lactic acid) blends.
AB  - Blends of poly(L-lactic acid) (PLLA) with two kinds of poly[(R)-3
      hydroxybutyrate] (PHB) having different molecular weights, commercial-grade
      bacterial PHB (bacterial-PHB) and ultrahigh molecular weight PHB (UHMW-PHB), were
      prepared by the solvent-casting method and uniaxially drawn at two drawing
      temperatures, around PHB's T(g) (2 degrees C) for PHB-rich blends and around
      PLLA's T(g) (60 degrees C) for PLLA-rich blends. Differential scanning
      calorimetry analysis showed that this system was immiscible over the entire
      composition range. Mechanical properties of all of the samples were improved in
      proportion to the draw ratio. Although PLLA domains in bacterial-PHB-rich blends
      remained almost unstretched during cold drawing, a good interfacial adhesion
      between two polymers and the reinforcing role of PLLA components led to enhanced
      mechanical properties proportionally to the PLLA content at the same draw ratio.
      On the contrary, in the case of UHMW-PHB-rich blends, the minor component PLLA
      was found to be also oriented by cold drawing in ice water due to an increase in
      the interfacial entanglements caused by the very long chain length of the matrix
      polymer. As a result, their mechanical properties were considerably improved with
      increasing PLLA content compared with the bacterial-PHB system. Scanning electron
      microscopy observations on the surface and cross-section revealed that a layered
      structure with uniformly oriented microporous in the interior was obtained by
      selectively removal of PLLA component after simple alkaline treatment.

PMID- 15244479
TI  - Dehydration of an ethanol/water azeotrope by novel organic-inorganic hybrid
      membranes based on quaternized chitosan and tetraethoxysilane.
AB  - To control swelling of quaternized chitosan (q-Chito) membranes, mixtures of q
      Chito as an organic component and tetraethoxysilane (TEOS) as an inorganic
      component were prepared using the sol-gel reaction, and novel q-Chito/TEOS hybrid
      membranes were formed. In the separation of an ethanol/water azeotrope by
      pervaporation, the effect of TEOS content on the water/ethanol selectivity of q
      Chito/TEOS hybrid membranes was investigated. Hybrid membranes containing up to
      45 mol % TEOS exhibited higher water/ethanol selectivity than the q-Chito
      membrane. This resulted from depressed swelling of the membranes by formation of
      a cross-linked structure. However, introduction of excess TEOS led to greater
      swelling of the hybrid membranes. Therefore, the water/ethanol selectivity of the
      hybrid membranes containing more than 45 mol % TEOS was lower than that of the q
      Chito membrane. The relationship between the structure of q-Chito/TEOS hybrid
      membranes and their permeation and separation characteristics during
      pervaporation of an ethanol/water azeotrope is discussed in detail.

PMID- 15244480
TI  - Evaluation of a novel poly(epsilon-caprolactone)-organosiloxane hybrid material
      for the potential application as a bioactive and degradable bone substitute.
AB  - A novel poly(epsilon-caprolactone)-organosiloxane hybrid material containing
      calcium salt (Si-O-PCL) was prepared and evaluated as a bioactive and degradable
      bone substitute material. The Si-O-PCL hybrid was synthesized by the end-capping
      of 3-isocyanatopropyl triethoxysilane with alpha,omega-hydroxyl PCL following sol
      gel reaction with calcium nitrate tetrahydrate. Its tensile mechanical properties
      were evaluated, and additional specimens were exposed to simulated body fluid
      (SBF) for the time range from 3 h to 7 days. The SBF exposure led to the
      deposition of a layer of apatite crystals on the surface of the Si-O-PCL hybrid
      within 9 h of soaking. The tensile strength was around 18 MPa, Young's modulus
      was around 200 MPa, and the strain at break was around 290%. This material is
      likely to have a potential application as a bioactive and degradable bone
      substitute because of its apatite forming ability, biodegradability, and
      mechanical properties comparable to those of human cancellous bone.

PMID- 15244481
TI  - Protamine assembled in multilayers on colloidal particles can be exchanged and
      released.
AB  - Biocomposite thin films assembled on colloidal particles by means of layer-by
      layer adsorption have been suggested as drug carriers and diagnostic devices.
      Protamine (PRM)/dextransulfate (DXS) and protamine/bovine serum albumine (BSA)
      multilayers were fabricated on colloidal silica and subsequently investigated by
      means of fluorescence activated cell sorting (FACS) and microelectrophoresis.
      Fluorescein labeled polyelectrolytes were embedded at different positions in the
      multilayers as a marker for layer growth. FACS showed that PRM and DXS formed
      regular growing stable multilayers, yet adsorbed PRM can be nevertheless
      exchanged with PRM in solution during layer formation and also after the
      multilayer formation has been completed. Up to 90% of the PRM pool was available
      for exchange. PRM together with BSA as demonstrated by SFM did not form
      multilayers under the applied conditions although the zeta-potential, commonly
      used as an indicator for stepwise adsorption, observed characteristic
      alternations. The capability of bound PRM to exchange with PRM in solution is
      attributed to its relatively small size. The demonstrated exchange may have
      importance in designing multilayers with smart release features. Furthermore,
      FACS proved to be a rather suitable means to quantify the aggregation behavior
      during coating and washing. Singulets, doublets, triplets, and aggregates of
      higher order could be clearly resolved. The aggregation of particles coated with
      PRM/DXS layers was higher than that of silica particles coated with PAH/PSS
      layers. In the first case about 50% of all recorded events are attributed to
      aggregats, while the PAH/PSS coating produced only about 10% aggregates.

PMID- 15244482
TI  - Identification of the Anabaena sp. strain PCC7120 cyanophycin synthetase as
      suitable enzyme for production of cyanophycin in gram-negative bacteria like
      Pseudomonas putida and Ralstonia eutropha.
AB  - The cyanophycin synthetase gene cphA1 encoding the major cyanophycin synthetase
      (CphA) of Anabaena sp. strain PCC7120 was expressed in Escherichia coli
      conferring so far the highest specific CphA activity to E. coli (6.7 nmol
      arginine per min and mg protein). CphA1 and cphA genes of Synechocystis sp.
      strains PCC6803 and PCC6308 and Synechococcus strain MA19 were also expressed in
      wild types and polyhydroxyalkanoate-negative (PHA) mutants of Pseudomonas putida
      and Ralstonia eutropha. Recombinant strains of these bacteria expressing cphA1
      accumulated generally more cyanophycin (23.0 and 20.0% of cellular dry matter,
      CDM, respectively) than recombinants expressing any other cphA (6.8, 9.0, or
      15.8% of CDM for P. putida strains and 7.3, 12.6, or 14.1% of CDM for R.
      eutropha). Furthermore, PHA-negative mutants of P. putida (9.7, 10.0, 17.5, or
      24.0% of CDM) and R. eutropha (8.9, 13.8, 16.0, or 22.0% of CDM) accumulated
      generally more cyanophycin than the corresponding PHA-positive parent strains
      (6.8, 9.0, 15.8, and 23.0% of CDM for P. putida strains and 7.3, 12.6, 14.1, or
      20.0% of CDM for R. eutropha strains). Recombinant strains of Gram-positive
      bacteria (Bacillus megaterium, Corynebacterium glutamicum) were not suitable for
      cyanophycin production due to accumulation of less cyanophycin and retarded
      release of cyanophycin. PHA-negative mutants of P. putida and R. eutropha
      expressing cphA1 of Anabaena sp. strain PCC7120 are therefore preferred
      candidates for industrial production of cyanophycin.

PMID- 15244483
TI  - Properties and microstructure of thermo-pressed wheat gluten films: a comparison
      with cast films.
AB  - Wheat gluten films were prepared by thermo-pressing, and their mechanical
      properties were compared to those of cast films. The stress-strain relationship
      was established for films with various amounts of glycerol. Both relationships
      were quite different, revealing a different network organization. Thermo-pressed
      films presented higher stress values than cast films, but the effect of the
      glycerol amount was similar in both cases, an increase of the glycerol amount
      leading to a decrease of both films stress. The glycerol influence on the strain
      at break of thermo-pressed films was very limited, with strain values reaching a
      maximum around 200%. The role of disulfide bridges on themomoulded films
      mechanical properties was investigated, and it was shown that some rearrangements
      and a significative protein insolubilization occurred during the process. The
      effective flow porosity of the protein network for thermo-pressed films was
      estimated by water capillary rise measurements to about 7%. Scanning electron
      microscopy was used to obtain some information about the microstructure of both
      cast and thermo-pressed films.

PMID- 15244484
TI  - Novel poly(ethylene glycol) embedded polyamidoamine side chain dendritic
      polyurethane architecture: synthesis and preliminary studies on the cytotoxicity
      and interaction with tryptophan molecule.
AB  - Novel polyamidoamine (PAMAM) side chain dendritic polyurethane (SCDPU-PEG)
      architecture embedded with poly(ethylene glycol) has been prepared. This novel
      SCDPU-PEG was characterized by means of FT-IR, NMR ((1)H and (13)C)
      spectroscopic, GPC, and thermal analyses and intrinsic viscosity measurements.
      Studies on cytotoxicity by means of MTT assay and interaction of L-tryptophan
      with this polydendron have been achieved.

PMID- 15244485
TI  - Thermal degradation processes of end-capped poly(L-lactide)s in the presence and
      absence of residual zinc catalyst.
AB  - Thermal degradation processes of end-capped poly(L-lactide)s (PLLAs) were
      investigated by means of several thermoanalytical techniques under both
      isothermal and nonisothermal conditions. Based on the thermogravimetric analysis,
      it was found that two distinct processes at temperatures below and above 330
      degrees C were existed in the nonisothermal degradation for PLLA samples
      depending on the amounts of residual zinc compounds from synthesis process.
      Isothermal degradation experiments at different temperature regions showed that
      the sample weight of PLLA decreased linearly with time in both cases, whereas the
      changes in molecular weight revealed different tendency for the temperature. On
      the basis of characterization of the residual PLLA molecules after isothermal
      degradation at 330 degrees C, it was confirmed that the omega chain end of the
      residual molecules was an acrylic ester unit. Majority of volatile products
      during thermal degradation of PLLA was the lactide regardless of the degradation
      temperature. From these results, it is concluded that, during the thermal
      degradation of PLLA samples in the presence of large amounts of residual zinc
      compounds, the zinc compounds catalyze both the intermolecular
      transesterification generating PLLA with low molecular weights and the selective
      unzipping depolymerization of PLLA with low molecular weights at temperatures
      below 330 degrees C. In contrast, the primary reaction of thermal degradation for
      PLLA in the absence of residual zinc compounds above 330 degrees C is a
      competition between the random chain scission via a cis-elimination reaction and
      the cyclic rupture via intramolecular transesterification of PLLA molecules. In
      addition, it was evidenced that the racemization of lactic acid units in the main
      chain of PLLA molecules occurred at temperatures above 330 degrees C.

PMID- 15244486
TI  - Biomimetic cooperative interactions of dried cross-linked poly(N-6
      aminohexylacrylamide) with binary mixtures of solvent vapors.
AB  - Biomimetic cooperativity of hydration effect and effect of ethanol favorable for
      binding of bad organic sorbates were observed for their vapor sorption by cross
      linked poly(N-6-aminohexylacrylamide) (PNAHAA) in the absence of liquid phase.
      The vapor sorption isotherms were determined for these systems by the static
      method of gas chromatographic headspace analysis at 298 K. The hydration above
      0.09-0.13 g of H(2)O/(g of polymer) gives a cooperative increase in the PNAHAA
      binding affinity for benzene, cyclohexane, dioxane, and propanols up to a level
      which does not change by further hydration, indicating the polymer
      antiplasticization. Bad sorbates (dioxane, benzene) were observed to have a
      biomimetic cooperative influence on the binding of ethanol by the dried PNAHAA.
      This cooperativity does not occur in ternary systems with good nonhydroxylic
      sorbate acetonitrile.

PMID- 15244488
TI  - An economic model of 2-hour post-dose ciclosporin monitoring in renal
      transplantation.
AB  - BACKGROUND: Monitoring of microemulsion ciclosporin (cyclosporine; Neoral) by 2
      hour post-dose drug concentrations (C2) is an accurate measure of ciclosporin
      absorption efficiency and exposure, and appears superior to trough (C0)
      monitoring for prediction of rejection risk. A predictive decision model was used
      to determine if this approach also reduces total treatment costs in the first 12
      months after renal transplantation. METHODS: Parameter estimates for key clinical
      events were derived from the literature and from prospective pharmacokinetic
      studies comprising 234 adult HLA-non-identical renal graft recipients at seven
      Canadian centres. Patients were treated with microemulsion ciclosporin (Neoral),
      corticosteroids and azathioprine or mycophenolate mofetil. Using the perspective
      of the Canadian healthcare provider, total treatment costs for the C2 versus the
      C0 strategy were modelled over 12 months, and then remodelled using conservative
      estimates to extend the timeframe to 5 years. Health resources were valued in
      1999 Canadian dollars. RESULTS: The incidence of acute rejection was estimated to
      be 25% at 1 year in patients monitored by C0 and 18% in those monitored by C2.
      Patient survival was considered to be independent of monitoring strategy, and
      graft loss was predicted to be 1.4% lower in the C2 group. The studies suggested
      no important differences in comorbidity and the costs of C0 and C2 monitoring and
      ambulatory-based adverse events were held equivalent. Using these inputs, the
      average cost per patient for the first year post-transplant was Can dollars
      46,857 for C0 monitoring and Can dollars 45,306 for C2 monitoring, rising to Can
      dollars 146,879 and Can dollars 142,569 after 5 years. The predicted cost for
      initial hospitalisation was Can dollars 11,280 for C0 and Can dollars 10,806 for
      C2 monitoring. The cost of maintenance immunosuppressive drug use, graft loss and
      dialysis was Can dollars 19,098 in the C0 group and Can dollars 18,612 in the C2
      group, while acute rejection treatment costs were Can dollars 2169 and Can
      dollars 1577, respectively. An additional Can dollars 14,310 was consumed by
      other events, including repeat hospitalisation, for each group. Sensitivity
      analysis indicated that the most influential parameters affecting savings due to
      C2 monitoring were a reduction in the duration of initial and follow-up
      hospitalisations and reduced risks of acute rejection and subsequent graft loss.
      CONCLUSIONS: Compared with traditional trough concentration monitoring,
      ciclosporin monitoring at 2 hours post-dose produced a predicted saving of Can
      dollars 1551 during the first year after renal transplant. Although modelling
      assumptions become more restrictive over time, this projection allows a
      preliminary assessment of the long-term economic impact of the routine use of C2
      monitoring.

PMID- 15244489
TI  - From randomised clinical trials to clinical practice : a pragmatic cost
      effectiveness analysis of Paclitaxel in first-line therapy for advanced ovarian
      cancer.
AB  - INTRODUCTION: Paclitaxel plus cisplatin is considered to be the standard first
      line therapy for advanced ovarian cancer. Previous to this study, economic data
      on this combination resulted from randomised clinical trials (RCTs). Therefore,
      the objective of this study was to compare the clinical and economic outcomes
      associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC)
      regimens using a pragmatic perspective based on daily clinical practice in a
      French university hospital. METHOD: A retrospective cost-effectiveness analysis,
      from the hospital-payer perspective, was carried out as a before-after case study
      in fifty-nine consecutive women with verified International Federation of
      Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated
      between 1995 and 2000. Median overall survival (OS) was used as the primary
      endpoint. The quality-adjusted time was assessed by the quality-adjusted time
      without symptoms or toxicity (Q-TWiST) method. Direct medical costs were
      collected for each patient. Monetary values for French prices in the year 2000
      were used and converted to US dollars using an exchange rate of USD 1 = 7 French
      francs. Several univariate sensitivity analyses were carried out varying unit
      costs, medical practices and administration of paclitaxel. RESULTS: The
      incremental cost of the PC regimen was USD 10,716 per patient. OS and quality
      adjusted time were improved by 10.8 and 9.3 months with the PC regimen. The cost
      per life-year gained and per added QALY were USD 11,907 and USD 13,827,
      respectively. The robustness of the results was confirmed in sensitivity
      analyses. CONCLUSION: Our study suggests that PC may be a cost-effective regimen
      for advanced ovarian cancer in a French university hospital setting. We reported
      higher incremental costs and lower clinical benefits than RCT-based findings,
      suggesting that RCT-based findings were clearly balanced by our pragmatic
      approach based on clinical practices. Observational studies can provide
      complementary and balanced data for decision making.

PMID- 15244490
TI  - Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of
      osteoarthritis and rheumatoid arthritis patients in the UK.
AB  - INTRODUCTION: The objective of this study was to evaluate the potential economic
      implications of using etoricoxib versus non-selective NSAID alternatives in the
      treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in
      the UK. STUDY DESIGN: Decision-analytical modelling was used to calculate the
      expected costs and consequences of the use of etoricoxib compared with non
      selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus
      histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous
      treatment period of 1 year. METHODS: The model considered direct medical costs
      from the perspective of the UK National Health Service (NHS) and used data from
      phase IIb and III clinical trials of etoricoxib to determine probabilities of
      gastrointestinal (GI) events. Model outcomes were defined as resource-consuming
      GI-related events, including clinically evident gastroduodenal perforations,
      symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs
      ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002
      values) for the treatment of OA and RA as well as GI events were based on
      published literature and information available from UK-specific sources. MAIN
      OUTCOME MEASURES AND RESULTS: The model suggests that etoricoxib is cost saving
      compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus
      misoprostol. The model also suggests that etoricoxib is cost effective in terms
      of the incremental cost per QALY gained for non-selective NSAIDs alone (pound
      19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The
      incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non
      selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2
      antagonists. For patients without the presence of specific GI risk factors
      (history of GI event, corticosteroid use or disability), etoricoxib may be cost
      effective for patients over age 56 years, assuming a cost-effectiveness threshold
      of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in
      patients of all ages who had at least one specific GI risk factor. CONCLUSIONS:
      The model suggests, with its underlying assumptions and data, that etoricoxib is
      a cost-effective alternative to therapeutic regimens involving non-selective
      NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving
      and dominant over non-selective NSAIDs used together with a PPI or misoprostol.
      When compared with non-selective NSAIDs alone or non-selective NSAIDs co
      prescribed with H2 antagonists, the incremental cost per QALY gained with use of
      etoricoxib was within the generally accepted threshold for cost effectiveness
      (less than pound 30,000 per QALY gained).

PMID- 15244491
TI  - Economic assessment of the secondary prevention of ischaemic stroke with
      dipyridamole plus aspirin (Aggrenox/Asasantin) in France.
AB  - OBJECTIVE: To assess the cost effectiveness of aspirin 25 mg plus dipyridamole
      200 mg twice daily in the secondary prevention of ischaemic stroke, according to
      the French social security perspective, using efficacy data from the second
      European Stroke Prevention Study (ESPS-2). The ESPS-2 was a double-blind, placebo
      controlled clinical trial which assessed the efficacy of four secondary
      prevention strategies: (i) placebo; (ii) aspirin (acetylsalicylic acid) 25 mg
      twice daily; (iii) dipyridamole 200 mg twice daily; and (iv) aspirin 25 mg plus
      dipyridamole 200 mg twice daily. METHOD: We performed a cost-effectiveness
      analysis with Monte Carlo simulations to compute confidence intervals. We
      combined data from various sources including the Dijon Stroke Registry, Institut
      National de la Statistique et des Etudes Economiques, Etude du Cout de
      l'Infarctus Cerebral (Study of the Cost of Cerebral Infarction [ECIC]) study and
      the ESPS-2 trial. RESULTS: According to our findings, a preventive strategy with
      aspirin 25 mg plus dipyridamole 200 mg twice daily is associated with net
      benefits per avoided stroke recurrence amounting to USD 23,932 (95% CI -USD
      32,609, USD 35,772) compared with aspirin 25 mg twice daily alone, and USD 31,555
      (95% CI USD 4921, USD 74,515) compared with dipyridamole alone (1997 values).
      Sensitivity analysis demonstrated that dipyridamole plus aspirin was still cost
      effective when the average cost of adverse effects per episode (ignored in the
      original estimation of the cost-effectiveness ratios due to a lack of data) was
      assumed to be USD 8600 (50,000 French francs); this cost is unlikely as most of
      the adverse effects associated with aspirin plus dipyridamole are only slight to
      moderate in severity. CONCLUSIONS: In the secondary prevention of stroke in
      France, this study suggests, given its underlying assumptions and data, that
      aspirin 25 mg plus dipyridamole 200 mg twice daily is likely to be a cost
      effective strategy from the social security perspective, when compared with other
      relevant strategies that were evaluated in the ESPS-2 trial.

PMID- 15244492
TI  - Warfarin in the secondary prevention of thromboembolism in atrial fibrillation:
      impact of bioavailability on costs and outcomes.
AB  - BACKGROUND: The bioavailability of warfarin is an important factor affecting the
      achievement of therapeutic anticoagulation. It is uncertain whether less
      expensive generic preparations of warfarin would compromise prevention of
      thromboembolism or increase bleeding risk in patients with atrial fibrillation.
      OBJECTIVE: To compare the cost effectiveness of strategies using warfarin
      products with variable bioavailability in patients with a prior stroke or
      transient ischaemic attack related to atrial fibrillation. DESIGN: A Markov
      decision-analytic model simulating health and economic outcomes over 1 year using
      the perspective of a government provincial payer was created. Four strategies
      were compared (where F = 1 is the assumed bioavailability of the
      branded/reference product): (i) warfarin F = 1; (ii) warfarin F = 1.25; (iii)
      warfarin F = 0.80; and (iv) alternating warfarin F = 1.25 and 0.80 every other
      month. Direct medical costs for drugs, physician fees, laboratory testing and
      hospitalisation for morbid events were obtained from a government payer, a local
      accounting system and the medical literature. The cost of warfarin F = 1 was
      equivalent to the cost of the brand name warfarin and the cost of warfarin F not
      equal 1 was equivalent to generic warfarin. RESULTS: In our institution, warfarin
      F = 1 was similar in cost to the other three strategies (Can dollars 1361 vs Can
      dollars 1334-1613) and may be more effective than switching between generic
      preparations which have bioavailabilities at the extremes of acceptable limits
      (thromboembolism and bleeds 7. 1% vs 9.3%). CONCLUSIONS: In patients with atrial
      fibrillation and a prior ischaemic stroke or transient ischaemic attack, the use
      of one warfarin agent within the range of acceptable bioavailability can be
      considered economically attractive from the healthcare perspective.

PMID- 15244493
TI  - On cost effectiveness and sample size in clinical trials.

PMID- 15244496
TI  - Metabolites and bioequivalence: past and present.
AB  - Although it is widely recognised that measurement of metabolite concentrations is
      crucial to understanding the clinical pharmacology characteristics of a new
      molecular entity, a clear consensus on the role of metabolites in the assessment
      of bioequivalence has never been achieved within the scientific community.
      However, a regulatory policy for the role of metabolites in bioavailability and
      bioequivalence has been established by the US FDA. One school of thought believes
      that the parent drug alone is sensitive to picking up formulation differences,
      whereas another school of thought believes that establishing bioequivalence
      criteria on all the species that contribute to safety and efficacy is the only
      way to ensure the switchability of two products. In this paper, a brief review of
      the pharmacokinetics of metabolites under different scenarios is presented and
      the history of the role of metabolites in the assessment of bioequivalence is
      summarised. Relevant examples from the literature illustrating conflicting
      opinions on the need for the measurement of metabolites in bioequivalence studies
      are given. Cases from the literature in which the parent drug is able to meet the
      90% confidence intervals while the metabolite(s) fail to do so, and vice versa,
      are presented to illustrate the difficulty in choosing the pertinent entity to
      measure. The relevant current US FDA policy and guidelines related to
      bioavailability and bioequivalence are discussed and contrasted with the rules
      and regulations applicable in Canada and Europe.

PMID- 15244497
TI  - Tazarotene does not affect the pharmacokinetics and efficacy of a
      norethindrone/ethinylestradiol oral contraceptive.
AB  - OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic interaction
      between oral tazarotene and an oral contraceptive containing norethindrone 1mg
      and ethinylestradiol 0.035 mg (Ortho-Novum 1/35). DESIGN: Two separate open
      label, parallel-group, single-centre, pharmacokinetic and pharmacodynamic
      interaction studies. PARTICIPANTS AND METHODS: Twenty-seven healthy women (age 20
      55 years) completed Study I, with a duration of 64 days during three consecutive
      menstrual cycles. Ortho-Novum 1/35 was taken once daily from study day 0 (first
      cycle day 1) to day 61 (third cycle day 6), and oral tazarotene 1.1 mg was
      coadministered daily from study day 34 (second cycle day 7) to day 61. Twenty
      nine healthy women (age 20-44 years) completed Study II, with a duration of 75
      days during three consecutive menstrual cycles. Ortho-Novum 1/35 was taken once
      daily from study day 0 (first cycle day 1) to day 74 (third cycle day 19), and
      oral tazarotene 6 mg was coadministered daily from study day 48 (second cycle day
      21) to day 74. In both studies, the pharmacokinetics of tazarotenic acid on study
      day 61 (third cycle day 6) were evaluated from plasma tazarotenic acid
      concentrations. Pharmacokinetic parameters of plasma norethindrone and
      ethinylestradiol were compared before and after tazarotene administration (cycle
      day 6 of the second and third cycles, respectively). Serum luteinising hormone
      (LH) and follicle-stimulating hormone (FSH) concentrations were compared before
      and after tazarotene administration (cycle days 2, 4 and 6 of the second and
      third cycles, respectively). In Study II, serum progesterone concentrations were
      also determined on cycle days 18 and 20 of the second and third cycles.
      Tazarotenic acid was determined by liquid chromatography-tandem mass
      spectrometry. Ethinylestradiol and norethindrone were determined by gas
      chromatography-mass spectrometry. LH and FSH were assayed by microparticle enzyme
      immunoassay in Study I and by double-antibody radioimmunoassay in Study II.
      Progesterone was determined by solid-phase radioimmunoassay. RESULTS: In Study I
      (tazarotene 1.1 mg), the area under the plasma concentration-time curve from zero
      to 24 hours (AUC24) and the peak concentration in plasma (Cmax) for tazarotenic
      acid were 121 +/- 27 microg. h/L and 28.9 +/- 9.4 microg/L (mean +/- SD),
      respectively. In Study II (tazarotene 6 mg), AUC24 and Cmax for tazarotenic acid
      were 379 +/- 78 microg. h/L and 111 +/- 37 microg/L (mean +/- SD), respectively.
      In both studies, for both norethindrone and ethinylestradiol, the 90% CIs of
      AUC24 and Cmax on cycle day 6 before and after tazarotene administration were
      within the 80-125% boundary. In Study I, the 90% CIs of serum FSH and LH
      concentrations on cycle day 4 were within the 80-125% boundary. FSH and LH
      concentrations on cycle day 6 were marginally/partially outside the 80-125%
      boundary as a result of high variability. However, the mean FSH and LH serum
      concentrations on cycle day 6 of the third cycle were lower than those of the
      second cycle. In Study II, the 90% CIs of serum FSH, LH and progesterone
      concentrations were all within the 80-125% boundary, except for LH on cycle day
      2. LH concentrations on cycle day 2 were marginally/partially outside the 80-125%
      boundary as a result of high variability. However, the mean serum LH
      concentration on cycle day 2 of the third cycle was lower than that of the second
      cycle. CONCLUSIONS: Oral tazarotene up to 6 mg once daily does not affect the
      pharmacokinetics and efficacy of Ortho-Novum 1/35.

PMID- 15244498
TI  - Evaluation of pharmacokinetic interactions after oral administration of
      mycophenolate mofetil and valaciclovir or aciclovir to healthy subjects.
AB  - OBJECTIVE: To investigate a potential pharmacokinetic interaction between
      mycophenolate mofetil (MMF) and aciclovir or valaciclovir. STUDY DESIGN AND
      PARTICIPANTS: Fifteen healthy subjects were enrolled in a prospective,
      randomised, open-label, single-dose, cross-over study conducted at a single
      centre. Subjects received each of the following five oral treatments: (i)
      aciclovir 800 mg alone; (ii) valaciclovir 2 g alone; (iii) MMF 1 g alone; (iv)
      valaciclovir 2 g + MMF 1 g; and (v) aciclovir 800 mg + MMF 1 g. The following
      pharmacokinetic parameters were estimated for aciclovir, mycophenolic acid (MPA)
      and its inactive glucuronide metabolite (MPAG) from the plasma concentration-time
      data using noncompartmental methods: area under the concentration-time curve from
      zero to infinity (AUC infinity), terminal elimination half-life (t1/2z), peak
      concentration (Cmax) and time to Cmax (tmax). The renal clearance (CLR) of
      aciclovir was also calculated. These parameters were compared when aciclovir or
      valaciclovir were coadministered with MMF relative to aciclovir, valaciclovir or
      MMF given alone. RESULTS AND DISCUSSION: Aciclovir Cmax, tmax and AUC infinity
      were significantly increased by 40%, 0.38 hour and 31%, respectively, following
      coadministration of aciclovir and MMF, whereas aciclovir t1/2z was significantly
      decreased by 11%. Following coadministration of valaciclovir and MMF, aciclovir
      pharmacokinetic parameters were not significantly modified except for tmax (about
      0.5 hour shorter with MMF). MPA and MPAG pharmacokinetic parameters were not
      significantly modified following coadministration of MMF with valaciclovir or
      aciclovir except for MPAG AUC infinity, which was decreased by 12% with
      valaciclovir. Our results are similar to those reported in the literature, except
      for MPAG AUC. In urine, following coadministration of aciclovir and MMF,
      aciclovir CLR was significantly decreased by 19%. Competition between MPAG and
      aciclovir for renal tubular secretion could partly explain this phenomenon.
      Following coadministration of valaciclovir and MMF, aciclovir CLR was not
      significantly modified. CONCLUSION: In healthy subjects, interactions are
      observed after coadministration of MMF and aciclovir, but the extent of the
      interactions is unlikely to be of clinical significance. These interactions
      should be investigated in patients with abnormal renal function.

PMID- 15244499
TI  - New advances and potential therapies for the treatment of asthma.
AB  - Asthma is a disease of the airways with an underlying inflammatory component. The
      prevalence and healthcare burden of asthma is still rising and is predicted to
      continue to rise in the current century. Inhaled beta(2)-adrenoceptor agonists
      and corticosteroids form the basis of the treatments available to alleviate the
      symptoms of asthma. There is a need for novel, safe treatments to tackle the
      underlying inflammation that characterizes asthma pathology. Furthermore, there
      is a requirement for new treatments to be developed as oral therapy in order to
      alleviate patient compliance issues, especially in children. A multitude of new
      approaches and new targets are being investigated, which may provide
      opportunities for novel therapeutic interventions in this debilitating disease.
      For simplicity, these approaches can be divided into two categories. The first
      comprises therapies directed against specific components or steps seen in
      allergic asthma. By 'components' we mean the key inflammatory cells (T cells [in
      particular T(h)2], B cells, eosinophils, mast cells, basophils and antigen
      presenting cells [APC]) and mediators (immunoglobulin E [IgE], cytokines,
      histamines, leukotrienes and prostanoids) believed to be involved in the chronic
      inflammation seen in asthma. By 'steps' we mean the allergic response, such as
      antigen processing and presentation, T(h)2-cell activation, B-cell isotype
      switching, mast cell involvement and airway remodeling. The other category of
      novel approaches to disease modification in asthma encompasses general anti
      inflammatory therapies including phosphodiesterase 4 (PDE4) inhibitors, p38
      mitogen-activated protein kinase (MAPK) inhibitors, peroxisome proliferator
      activated receptor-gamma (PPARgamma) agonists, and lipoxins.

PMID- 15244500
TI  - Blood products for hemophilia: past, present and future.
AB  - Hemophilia is an inherited bleeding disorder, which in its severe form is
      characterized by recurrent hemarthrosis and internal bleeding. In the absence of
      effective treatment the prognosis is poor, but the development of blood products
      in the last few decades has transformed the outlook, and patients can now live
      essentially normal lives. Treatment options vary around the world, with
      cryoprecipitate still the mainstay of therapy in many developing countries. Many
      patients were infected with hepatitis and/or HIV through the use of coagulation
      factor concentrates before the introduction of physical methods of viral
      inactivation in the mid-1980s. In more affluent countries, the debate in recent
      years has focused on the relative merits of plasma versus recombinant products.
      Coagulation factor concentrates are expensive, and cost-benefit and quality-of
      life studies will assume an increasing importance in guiding the selection of
      products. Looking to the future, genetic engineering offers the potential to
      create coagulation factors with enhanced properties, such as reduced
      immunogenicity and prolonged half-life. Transgenic animals are a potential source
      of therapeutic materials. Several trials of gene therapy for hemophilia are
      already underway.

PMID- 15244495
TI  - Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ
      transplantation.
AB  - The aim of this review is to analyse critically the recent literature on the
      clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ
      transplant recipients. Dosage and target concentration recommendations for
      tacrolimus vary from centre to centre, and large pharmacokinetic variability
      makes it difficult to predict what concentration will be achieved with a
      particular dose or dosage change. Therapeutic ranges have not been based on
      statistical approaches. The majority of pharmacokinetic studies have involved
      intense blood sampling in small homogeneous groups in the immediate post
      transplant period. Most have used nonspecific immunoassays and provide little
      information on pharmacokinetic variability. Demographic investigations seeking
      correlations between pharmacokinetic parameters and patient factors have
      generally looked at one covariate at a time and have involved small patient
      numbers. Factors reported to influence the pharmacokinetics of tacrolimus include
      the patient group studied, hepatic dysfunction, hepatitis C status, time after
      transplantation, patient age, donor liver characteristics, recipient race,
      haematocrit and albumin concentrations, diurnal rhythm, food administration,
      corticosteroid dosage, diarrhoea and cytochrome P450 (CYP) isoenzyme and P
      glycoprotein expression. Population analyses are adding to our understanding of
      the pharmacokinetics of tacrolimus, but such investigations are still in their
      infancy. A significant proportion of model variability remains unexplained.
      Population modelling and Bayesian forecasting may be improved if CYP isoenzymes
      and/or P-glycoprotein expression could be considered as covariates. Reports have
      been conflicting as to whether low tacrolimus trough concentrations are related
      to rejection. Several studies have demonstrated a correlation between high trough
      concentrations and toxicity, particularly nephrotoxicity. The best predictor of
      pharmacological effect may be drug concentrations in the transplanted organ
      itself. Researchers have started to question current reliance on trough
      measurement during therapeutic drug monitoring, with instances of toxicity and
      rejection occurring when trough concentrations are within 'acceptable' ranges.
      The correlation between blood concentration and drug exposure can be improved by
      use of non-trough timepoints. However, controversy exists as to whether this will
      provide any great benefit, given the added complexity in monitoring.
      Investigators are now attempting to quantify the pharmacological effects of
      tacrolimus on immune cells through assays that measure in vivo calcineurin
      inhibition and markers of immunosuppression such as cytokine concentration. To
      date, no studies have correlated pharmacodynamic marker assay results with
      immunosuppressive efficacy, as determined by allograft outcome, or investigated
      the relationship between calcineurin inhibition and drug adverse effects. Little
      is known about the magnitude of the pharmacodynamic variability of tacrolimus.

PMID- 15244501
TI  - The role of recombinant hirudins in the management of thrombotic disorders.
AB  - Native hirudin is the most potent natural direct thrombin inhibitor currently
      known; it is capable of inhibiting not only fluid phase, but also clot-bound
      thrombin. Recombinant technology now allows production of recombinant hirudins (r
      hirudins), which are available in sufficient purity and quantity with essentially
      unaltered thrombin-inhibitory potency. As thrombin is known to play a key role in
      a number of thrombotic disorders, numerous studies focused on the impact of r
      hirudins on the clinical course in these diseases. R-hirudins provided
      significantly more stable anticoagulation than standard heparin, but demonstrated
      a relatively narrow therapeutic range with relevant bleeding risk even at
      clinically effective doses. In doses that are not associated with an increased
      bleeding risk, r-hirudins often failed to demonstrate significant superiority to
      heparin. To date, r-hirudins have a definite role in the treatment of heparin
      induced thrombocytopenia, where they markedly reduce the high risk of thrombosis.
      For prophylaxis of deep vein thrombosis, r-hirudins have been shown to be
      superior to both unfractionated and low molecular weight heparin, but are not
      extensively used in this indication. In acute coronary syndromes, a definite role
      of r-hirudins has not yet been firmly established. When applied in an appropriate
      dose as adjunct to thrombolysis in patients with acute myocardial infarction,
      randomized, controlled trials did not show a consistent benefit of r-hirudins,
      especially in the long-term. In patients undergoing coronary balloon angioplasty
      for acute coronary syndromes, promising effects in the early postprocedural phase
      did not translate to an improved outcome after 6 months. In patients with
      unstable angina pectoris, efficacy and safety of r-hirudins as primary
      antithrombotic therapy are still under debate. In the future, r-hirudins are to
      be compared with alternative or additional potent antithrombotic agents or
      treatment strategies. This comparison will ultimately lead to their final
      placement in the management of thrombotic disorders.

PMID- 15244502
TI  - Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo
      modulation of cytokine activities.
AB  - Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom
      replaces the central atom of oxygen. They are indicated in non-neoplastic
      diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease,
      and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma
      and bone metastases secondary to breast and prostate cancer. There is now
      extensive in vitro evidence suggesting a direct antitumor effect of
      bisphosphonates at different levels of action. Some new in vitro and in vivo
      studies support the cytostatic effects of bisphosphonates on tumor cells, and the
      effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion,
      and invasion, with particular attention to biological properties. Well designed
      clinical trials are necessary to investigate whether the antitumor potential of
      bisphosphonates may be clinically relevant. On the basis of their effects on
      macrophages, we may divide bisphosphonates into two distinct categories:
      aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus
      inducing an acute-phase response, and non-aminobisphosphonates that can be
      metabolized into macrophages and that may inhibit the inflammatory response of
      macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory
      response, in particular, related to modifications of the cytokine network.
      Several in vivo studies have demonstrated an acute-phase reaction after the first
      administration of aminobisphosphonates, with a significant increase in the main
      pro-inflammatory cytokines. However, a peculiar aspect concerning the action of
      non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the
      inhibition of the release of inflammatory mediators from activated macrophages,
      such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition
      of inflammatory responses is demonstrated in both in vivo and in vitro models.
      This activity suggests the use of non-aminobisphosphonates in several
      inflammatory diseases characterized by macrophage-mediated production of acute
      phase cytokines, as prevention of erosions in rheumatoid arthritis, and of
      loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing
      spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.

PMID- 15244503
TI  - Photodynamic treatment of the dermatophyte Trichophyton rubrum and its
      microconidia with porphyrin photosensitizers.
AB  - The application of photosensitizers for the treatment of fungal infections is a
      new and promising development within the field of photodynamic treatment (PDT).
      Dermatophytes, fungi that can cause infections of the skin, hair and nails, are
      able to feed on keratin. Superficial mycoses are probably the most prevalent of
      infectious diseases in all parts of the world. One of the most important
      restrictions of the current therapeutic options is the return of the infection
      and the duration of the treatment. This is especially true in the case of
      infections of the nail (tinea unguium) caused by Trichophyton rubrum, an
      anthropophilic dermatophyte with a worldwide distribution. Recently, we
      demonstrated that 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine
      trichloride (Sylsens B) and deuteroporphyrin monomethylester were excellent
      photosensitizers toward T. rubrum when using broadband white light. This study
      demonstrates the photodynamic activity of these photosensitizers with red light
      toward both a suspension culture of T. rubrum and its isolated microconidia. The
      higher penetration depth of red light is important for the PDT of nail
      infections. In addition, we tested the photodynamic activity of a newly
      synthesized porphyrin, quinolino-[4,5,6,7-efg]-7-demethyl-8-deethylmesoporphyrin
      dimethylester, displaying a distinct peak in the red part of the spectrum.
      However, its photodynamic activity with red light toward a suspension culture of
      T. rubrum appeared to be only fungistatic. Sylsens B was the best photosensitizer
      toward both T. rubrum and its microconidia. A complete inactivation of the fungal
      spores and destruction of the fungal hyphae was found. In studies into the
      photostability, Sylsens B appeared to be photostable under the conditions used
      for fungal PDT. A promising result of this study is the demonstration of the
      complete degradation of the fungal hyphae in the time after the PDT and the
      inactivation of fungal spores, both with red light. These results offer the
      ingredients for a future treatment of fungal infections, including those of the
      nail.

PMID- 15244504
TI  - Probing the active site of trypsin with rose bengal: insights into the
      photodynamic inactivation of the enzyme.
AB  - In this work the active site of trypsin has been probed with the dye rose bengal.
      The dye binds competitively to the enzyme, and it can be used as a probe of the
      active site of the enzyme. On the basis of the emission wavelength, the binding
      site of trypsin is relatively polar and is similar to that of acetone in its
      polarity. The triplet state of rose bengal is quenched by trypsin. This quenching
      may be caused by the tryptophan and tyrosine residues that are in the near
      vicinity of the trypsin active site. This quenching can compete with the
      formation of singlet oxygen from the excited triplet state of rose bengal. We
      demonstrate that the singlet oxygen involved in the photoinactivation of trypsin
      is produced by the free rose bengal in solution and the bound dye is incapable of
      producing singlet oxygen. This explains the lack of correlation between
      photoinactivation efficiency and sensitizer binding capability previously
      reported by Wade and Spikes.

PMID- 15244505
TI  - Correlation between oxygen consumption and photobleaching during in vitro
      photodynamic treatment with ATX-S10.Na(II) using pulsed light excitation:
      dependence of pulse repetition rate and irradiation time.
AB  - We revealed that in ATX-S10.Na(II)(13,17-bis (1-carboxypropionyl) carbamoylethyl
      8-etheny-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetraethyl porphyrin
      sodium)-mediated photodynamic therapy using 667 nm nanosecond-pulsed light
      excitation at a peak intensity of 2.0 MW/cm(2), phototoxicity increased with
      decreasing pulse repetition rate in the range of 5-30 Hz for A549 cell cultures.
      To examine the relation between the reaction mechanism and measured
      phototoxicity, we carefully measured the kinetics of photochemical oxygen
      consumption and photobleaching during irradiation of ATX-S10.Na(II)-sensitized
      A549 monolayer cultures. Measurements of oxygen consumption with a
      microelectrode, which was performed just above the cells, showed that there was
      no significant difference between the magnitudes of decrease in oxygen at the
      three repetition rates at the same cumulative fluence. Loss of ATX-S10.Na(II)
      fluorescence intensity also exhibited little repetition rate dependence when
      compared at the same cumulative fluence. We investigated the correlation between
      oxygen consumption and photobleaching during irradiation and obtained
      "fluorescence-oxygen diagrams." The diagrams showed dynamic changes between
      oxygen-dependent and oxygen-independent photobleaching at the higher repetition
      rates of 10 and 30 Hz, whereas such change was not clearly seen over the whole
      irradiation time at 5 Hz. These results suggest that the reduced phototoxicity at
      high repetition rates might be due to an oxygen-independent reaction. We presumed
      that the change in the reaction mechanism was associated with the local
      concentrations of the photosensitizer and oxygen in cells during irradiation.

PMID- 15244506
TI  - Molecular mechanism(s) for UV-B irradiation-induced glutathione depletion in
      cultured human keratinocytes.
AB  - Glutathione (GSH) plays a central role in maintenance of cellular redox
      homeostasis and protection against oxidative injury. Ultraviolet B (UV-B)
      irradiation-induced GSH depletion is believed to be involved in the pathogenesis
      of several cutaneous disorders. In this study, the molecular mechanism(s) of UV-B
      induced GSH depletion was investigated in cultured human keratinocytes, HaCaT
      cells. We found that UV-B irradiation caused GSH depletion in a dose- and time
      dependent manner in HaCaT cells. The mechanistic studies showed that UV-B-induced
      GSH depletion did not result from the GSH efflux. UV-B irradiation appeared to
      cause a slight decrease in enzymatic activity of gamma-glutamate cysteine ligase
      (GCL), a rate-limiting enzyme in GSH biosynthesis. UV-B irradiation resulted in
      the GCL cleavage through the activation of a caspase cascade. Inhibition of total
      caspase activity by the general caspase inhibitor, zVAD-fmk, partially reversed
      the UV-B-induced GSH depletion. More importantly, we found that UV-B irradiation
      could dramatically decrease the cystine uptake through the functional inhibition
      of the system Xc(-), a cystine transporter on the cell membrane. The results
      suggest that the inactivation of cystine transporter system Xc(-) was a major
      contributor to the UV-B-mediated decrease of GSH levels in human keratinocytes.

PMID- 15244507
TI  - Spatial distribution of upper-room germicidal UV radiation as measured with
      tubular actinometry as compared with spherical actinometry.
AB  - Chemical actinometry of UV germicidal irradiation using sections of quartz tubing
      as compared with quartz spheres as irradiation vessels has been investigated .
      Vessels were either 3 mm inner diameter quartz tubing, 46 cm in length (tubular
      actinometry), or 1 cm quartz spheres (spherical actinometry). The vessels
      containing an iodide/iodate actinometric solution were suspended from the ceiling
      at 24 positions in a room (6 x 6 m) containing five germicidal lamp fixtures in
      the corners and in the center of the room. The lamp fixtures were louvered
      collimating the radiation in the horizontal (x, y) plane. Hence, the tubes, which
      span the depth of the radiation field, essentially integrate the radiation along
      the z-axis for a given x, y position. The pseudospatial average fluence rate
      obtained using tubular actinometry was 18 mW/cm(2) for the volume contained in
      the upper 46 cm (18 inch) of the room. Spherical actinometry, which measured the
      fluence rate in the center of the beam, provided an average value of 32 mW/cm(2)
      over the volume of the beam. A comparison of the fluence rates obtained by these
      two methods allowed the average depth of the beam to be estimated as 26 cm. It is
      concluded that tubular actinometry is more advantageous than spherical
      actinometry for this application.

PMID- 15244508
TI  - Isolation and characterization of a novel cross-link lesion in d(CpC) induced by
      one-electron photooxidation.
AB  - Recently we reported the identification and characterization of a novel cross
      link lesion formed between two adjacent cytosines in d(CpC), which is the major
      product formed upon 365 nm photoirradiation of d(CpC) in the presence of 2-methyl
      1,4-naphthoquinone. In this study we discuss the isolation and structure
      characterization of another cross-link lesion formed under the same irradiation
      condition. Electrospray ionization mass spectroscopy, tandem mass spectrometry
      and two-dimensional nuclear Overhauser effect spectroscopy results demonstrate
      that the C6 carbon atom of the 5' cytosine and the N3 nitrogen atom of the 3'
      cytosine are covalently bonded. In addition, the 5' cytosine moiety is deaminated
      and the C5 carbon atom in this cytosine is oxidized to a carbonyl group.

PMID- 15244509
TI  - Tattoo pigments are cleaved by laser light-the chemical analysis in vitro provide
      evidence for hazardous compounds.
AB  - In the western world, more than 80 million people decorate their skin with
      tattoos. Tattoo colorants are injected into the skin, like medical drugs. Most
      tattoo colorants are industrial pigments, and chemical industries have never
      produced them for human use but only to stain consumer goods. Up to 10% of
      tattooed people request removal of their tattoos because of an improved self
      image or social stigmatization. In contrast to tattooing, physicians usually
      perform the tattoo removal. For that purpose laser light at very high intensities
      irradiates the skin to destroy the tattoo pigments. Based on a recent analysis of
      tattoo pigments, two widely used azo compounds were irradiated in suspension with
      laser and subsequently analyzed by using quantitative high-performance liquid
      chromatography and mass spectrometry. The high laser intensities cleaved the azo
      compounds, leading to an increase of decomposition products such as 2-methyl-5
      nitroaniline, 2-5-dichloraniline and 4-nitro-toluene, which are toxic or even
      carcinogenic compounds. Moreover, the results of the chemical analysis show that
      the tattoo colorants already contain such compounds before laser irradiation.
      Because of a high number of patients undergoing laser treatment of tattoos and
      based on the results of our findings in vitro, it is an important goal to perform
      a risk assessment in humans regarding laser-induced decomposition products.

PMID- 15244510
TI  - Awareness and high relative mortality rates in the asian pacific.

PMID- 15244512
TI  - Epidemiology of liver cancer: an overview.
AB  - The incidence of liver cancer varies widely throughout the world, with high rates
      in sub - Saharan Africa, eastern and southeastern Asia, and Melanesia and a low
      incidence in Northern and Western Europe and the Americas. Primary cancers of the
      liver in adults are of two main histological types: hepatocellular carcinoma,
      which is derived from hepatocytes, and cholangiocarcinoma, which is derived from
      the epithelial lining of the intrahepatic bile ducts. Hepatocellular cancer is a
      frequently occurring tumor in individuals in many developing countries, where
      several important risk factors have been demonstrated, including chronic
      infection with hepatitis B and C viruses and other environmental factors, such as
      exposure to aflatoxin, consumption of alcohol, and cigarette smoking. By
      contrast, cholangiocarcinoma is less common, accounting for only 7.7% of
      malignant tumors of the liver in the United States. However, in parts of
      Southeast Asia, cholangiocarcinoma occurs more frequently; it is responsible for
      more than 60% of liver tumors in northeastern Thailand. The geographic
      distribution worldwide coincides with endemic areas of the liver flukes,
      Opisthorchis viverrini and Clonorchis sinensis. The interaction between genes and
      the environment and the interplay of environmental factors, which include diet
      and other lifestyle parameters, illustrate the complexity underlying
      susceptibility.

PMID- 15244511
TI  - Cancer burden and trends in the Asian Pacific Rim region.
AB  - This paper describes the current cancer burden and time trends, discusses
      dominant risk factors and prevention and control strategies, and makes future
      projections for the top eight cancers (stomach, lung, liver, colon/rectum,
      esophagus, breast, cervix, and leukemia) in the Asian Pacific Rim region. The
      future cancer trends through to the year 2050 are projected based on population
      dynamics, including population growth and ageing. In 2000, the Asian Pacific Rim
      had over 3 million new cancer cases, over 2 million cancer deaths, and 5.4
      million people living with cancer. In 2050, 7.8 million new cancer cases and 5.7
      million deaths from cancer are projected. The current cancer burden and the
      future projection provide facts that cancer is and will be a very serious public
      health problem in the Asian Pacific Rim region and will assist public health
      officers and cancer researchers in the design and establishment of public health
      policies, prioritization of future research, and application of current knowledge
      in the prevention and control of cancer.

PMID- 15244513
TI  - Indian food ingredients and cancer prevention - an experimental evaluation of
      anticarcinogenic effects of garlic in rat colon.
AB  - The major food items of Indian cuisine include rice, wheat, diary products, and
      abundant fruits and vegetables. Beside these, there are several kinds of herbs
      and spices as important ingredients, containing many phytochemicals with
      medicinal properties, adding taste to Indian cuisine. An impressive body of data
      exists in support of the concept that Indian food ingredients can be used in
      preventive strategies aimed at reducing the incidence and mortality of different
      types of cancers because of their antioxidative, antimutagenic and
      anticarcinogenic properties. Vital ingredients used in Indian cooking include
      turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic
      is an indispensable ingredient of Indian food and this report concerns the
      chemopreventive efficacy of garlic in an azoxymethane induced rodent colon
      carcinogenesis model. The effect of garlic was evaluated in terms of aberrant
      crypt foci, putative preneoplastic lesions in the colon. In addition, cell
      proliferation and levels of apoptosis were determined and the expression of
      cyclooxygenase-2 protein was analyzed. Following treatment, significant
      inhibition of cell proliferation and induction of apoptosis, as well as
      suppression of cyclooxygenase-2 activity were observed, associated with
      significant reduction in the incidence of aberrant crypt foci. The study points
      to combined protective effects of garlic components on colon carcinogenesis.

PMID- 15244514
TI  - Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase
      genes and the susceptibility to esophageal and stomach cancer with smoking.
AB  - Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are
      major enzymes in the metabolism of folates, involved in DNA 'breaks', instability
      and hypomethylation. To investigate the possible relations between the TS 3'-UTR
      and MTHFR C677T polymorphisms and environmental factors impacting on risk of
      esophageal and stomach cancers, we conducted a case-control study in a high
      incidence region of China for these cancers. We recruited 138 esophageal and 155
      stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes
      were detected by RFLP assay, using PCR products. The frequency of the -6 bp
      homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians,
      although the present distribution was not in Hardy-Weinberg equilibrium. Ever
      smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54,
      1.60-7.82) for cases of esophageal and stomach cancers, respectively, when
      compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No
      combination between the TS and MTHFR genotypes gave increased ORs. The present
      results suggest that TS polymorphism may modify the risk of esophageal and
      stomach cancer with smoking, pointing to the necessity for further investigations
      with information on folate and methionine intake with a larger population.

PMID- 15244515
TI  - Defective repair of UV-induced DNA damage in cultured primary skin fibroblasts
      from Saudi thyroid cancer patients.
AB  - This study was conducted to examine the sensitivity of primary skin fibroblasts
      from Saudi thyroid cancer (TC) patients to ultraviolet (UV) irradiation. Cell
      survival was studied by a colony forming assay and DNA repair defects with a host
      cell reactivation (HCR) assay using UV-irradiated Herpes Simplex Virus (HSV). In
      addition, p53 gene expression was examined in the same TC cells exhibiting
      enhanced radiosensitivity. Skin fibroblasts from TC patients (n=4) showed
      significantly enhanced sensitivity to UV radiation. The average UV dose to reduce
      survival to 37% of the initial survival (D(37)) value (in Jm(-2)) for fibroblasts
      from TC patients was 4.6 (3.7-5.6) compared to 7.3 (6.3-8.3) for healthy
      individuals (n=3). UV-sensitive xeroderma pigmentosum (XP) cells, which were used
      as positive control, were found to be extremely sensitive with a D(37) value of
      0.6 Jm(-2). In a host cell reactivation assay, UV-irradiated HSV was tested for
      its plaque-forming ability (PFA), by plating infected fibroblasts from TC
      patients (used as host cells) on African Green Monkey (Vero) kidney cells to form
      plaques. A significant reduction in the PFA of the UV-irradiated virus (about
      three fold) on TC cells compared to fibroblasts from the healthy subjects was
      seen, suggesting a DNA-repair deficiency in the primary fibroblasts of the TC
      patients. Furthermore, no significant accumulation in radiation-induced p53
      expression was observed in cells from the TC patients. Our results, based on a
      relatively small group of subjects, indicate that Saudi TC patients primary
      fibroblasts (non-cancerous in nature) may be carriers of cancer-susceptible
      gene(s) arising from defective DNA repair/processing. These results warrant a
      larger study to investigate the role of UV-induced bulky DNA damage in thyroid
      cancer susceptibility.

PMID- 15244516
TI  - Experience with a self-administered device for cervical cancer screening by Thai
      women with different educational backgrounds.
AB  - BACKGROUND: This descriptive study was carried out to test the acceptability of a
      self-administered device for cervical cancer screening and assess certain risk
      factors in relation to the cancer in two districts of Khon Kaen province in
      Northeast Thailand. METHODS: A total of 354 women from the villages were selected
      (including 143 teachers from secondary and primary schools; 24 health officers
      from the rural health centres, and 37 nurses from the University Hospital, Khon
      Kaen University). The Kato device was introduced and used by the women, who were
      then asked to give their opinion on its usage. RESULTS: The Kato device was
      generally well accepted by the women. However, many of those with a higher
      educational background were more sceptical towards the device than their
      counterparts from the villages. CONCLUSIONS: A suitable approach to strengthen
      the control of cervical cancer in the rural areas of Thailand might be to
      introduce the Kato device as an integral part of primary health care. The
      introduction of the device should go along with health education on the
      importance of avoiding infection with the papilloma viruses. This message should
      be transmitted to both females and males.

PMID- 15244518
TI  - Retinoblastoma in Karachi, Pakistan.
AB  - The objective was to assess epidemiologic aspects of retinoblastoma development
      in Karachi, Pakistan. Incident cases, diagnosed clinically or microscopically and
      registered at Karachi Cancer Registry (KCR) during 1(st)January 1998 to 31(st)
      December 2002 were reabstracted, rechecked and reanalyzed for this purpose. One
      hundred and one cases of retinoblastoma were reported to KCR over the 5 years
      (1998-2002). Fifty-seven were residents of Karachi, 34 (59.6%) males and 23
      (40.4%) females. The gender ratio (M:F) was 1.5. The mean age at diagnosis was
      3.96 years (95% CI 2.92; 4.99) and 3.85 years (95% CI 2.72; 4.98) in males and
      females respectively. The annual crude incidence of retinoblastomas in Karachi
      was 4.0/100,000 and 2.4/100,000 in children under the age of 5 and 10 years
      respectively, the corresponding age standardized rates being 5.3/100,000 and
      4.8/100,000. The age groups at risk of developing retinoblastoma, associated
      morbidity and possibility of almost 100% 5-year survival with available
      treatments, calls for ophthalmologic screening of all infants below 1 year, and
      high-risk children until the age of 7 years. In order to detect retinoblastoma,
      as early as possible, health education for parents and health providers, and
      improved training of ophthalmologists is essential. Genetic testing for siblings
      and children of retinoblastoma cases and identification of high-risk children
      would be helpful, but lacks financial feasibility in developing countries at
      present. Future health care planning should focus on capacity building for
      neonatal ophthalmologic screening, handling of parents'and children'emotional
      reactions and opportunities for education, occupational training and cosmetic
      rehabilitation for surviving retinoblastoma patients.

PMID- 15244517
TI  - Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by
      diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and
      inhibition of nitric oxide production.
AB  - Selenium, an essential micronutrient, plays important roles against different
      diseases, including several types of cancer. In the present study, antioxidative
      and chemopreventive properties of a synthetic organoselenium compound,
      diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a)
      anthracene - croton oil induced two-stage mouse skin carcinogenesis model. The
      compound was administered orally to carcinogen-treated mice at two different non
      toxic doses, 2mg/kg. b.w. and 3mg/kg. b.w. Significant inhibition in the
      incidence of papilloma formation (53-80%) as well as in the cumulative numbers of
      papillomas per papilloma bearing mouse were observed in the treated groups as
      compared to the carcinogen control group. The compound was also found to
      upregulate significantly different phase II detoxifying enzymes such as
      glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin
      cytosol when measured after 15 days and also after 12 weeks of the first 7,12
      dimethylbenz (a) anthracene treatment. Lipid peroxidation measured with reference
      to thiobarbituric acid reactive substances in skin microsomes was significantly
      inhibited (p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate.
      Considerable inhibition of the level of nitric oxide production in peritoneal
      macrophages was observed after 12 weeks (p<0.05). Thus the compound appears to
      exert chemopreventive activity in terms of papilloma formation, which may be
      through modulation of cutaneous lipid peroxidation, the phase II detoxifying
      enzyme system and nitric oxide production.

PMID- 15244519
TI  - Knowledge, attitude and safe behaviour of nurses handling cytotoxic anticancer
      drugs in Ege University Hospital.
AB  - Many antineoplastic drugs are known to be carcinogenic, teratogenic and mutagenic
      to humans. There is thus a potential risk due to occupational exposure to
      cytotoxic drugs (CDs). Nurses and pharmacists are the main groups that are
      exposed to these drugs in the ambulatory care and hospital settings. An analytic
      cross sectional study was here carried out in order to evaluate the level of
      knowledge of nurses on the health effects and the routes of exposure to CDs, to
      clarify the protective measures while handling these agents and to determine the
      influence of this knowledge on clinical attitudes, behaviour and actual usage of
      safety measures. The level of knowledge of the nurses concerning antineoplastics
      was not satisfactory. Findings for nurses' safety behaviour and usage of
      recommended health safety measures showed that, notwithstanding the rules and
      regulations pertaining to CDs, nurses did not comply with them fully. In service
      training is a very effective tool to increase the level of knowledge. This study
      also revealed the necessity for improvement of the working environment and the
      availability of appropriate protective equipment.

PMID- 15244520
TI  - Decreasing trend in the incidence of stomach cancer in Mumbai, India, during 1988
      to 1999.
AB  - The time trend in incidence of stomach cancer in males and females in Mumbai,
      India during 1988 to 1999 was estimated using data collected by the Bombay
      Population-based Cancer Registry. During the 12-year period, a total of 3657
      stomach cancer cases (3.9% of all cancers) were registered by the Bombay
      Population-based Cancer Registry of which 2467 (5.1% of all male cancers) were in
      males and 1184 (2.6% of all female cancers) in females. For evaluation of the
      trend, we applied a linear regression model based on the logarithm of the
      observed incidence rates. The annual percentage changes were also computed for
      the incidence rates for evaluating the time trend. A statistically significant
      decreasing trend in the overall age-adjusted incidence rates of stomach cancer
      was observed during the period 1988 to 1999, with an yearly decrease of 4.44% in
      males and 2.56% in females. This decrease was most striking in males in the age
      groups 40-59 and 60+, and in females only in the age group 40-59. The probability
      estimates indicated that one out of every 92 men and one out of every 187 women
      will contract a stomach cancer at some time in their whole life and 95% of the
      chance is after his or her 40th birthday. The decreasing trend in the age
      adjusted incidence rates of stomach cancer in both the sexes indicates that there
      is a critical change in the etiology of this cancer. The findings may provide
      clues relating to various life-style and environmental changes impacting on
      stomach cancer incidence.

PMID- 15244521
TI  - Population-based survival from cancers having a poor prognosis in Mumbai
      (Bombay), India.
AB  - BACKGROUND: Oesophagus, stomach, pancreas and lung cancers contribute more than
      35% of the total cancer incidence in Mumbai and survival rates for these cancers
      are very poor in most populations in the world. The authors here report and
      discuss the population-based survival from these cancers in Mumbai, India.
      METHODS: Follow-up information on 5717 cancers patients having a low prognosis,
      registered in the Mumbai Population-Based Cancer Registry for the period 1987
      1991, was obtained by a variety of methods, including matching with death
      certificates from the Mumbai vital statistics registration system,
      postal/telephone enquiries, home visits and scrutiny of medical records. The
      survival for each case was determined as the duration between the date of
      diagnosis and date of death, loss to follow-up or the closing date of the study
      at the end of 1996. Cumulative observed and relative survival rates were
      calculated by the Hakulinen Method. For comparison of results with other
      populations, age-standardized relative survival (ASRS) was calculated by directly
      standardizing age specific relative survival to the specific age distributions of
      the estimated global incidence of major cancers in 1985. The log rank test was
      used with univariate analysis to identify the potentially important prognostic
      variables. The variables showing statistical significance in univariate analysis
      were introduced stepwise into a Cox Regression model to identify the independent
      predictors of survival. RESULTS: The 5-year relative survival rates were 11.8%
      for oesophagus, 10.1% for the stomach, 4.1% for the pancreas, and 7.0% for lung.
      Females had higher survival rates than males, except with lung cancer. Lower
      survival was observed for those younger than 35 years for all 4 sites. For each
      site, survival declined with advancing age. Single patients who remained
      unmarried had better survival, except with pancreatic cancer. For all sites
      Muslims had a better survival and Christians had a lower survival as compared to
      Hindus. Education did not show any pattern for any site. Survival decreased
      rapidly with advancing clinical extent of disease for all sites. Survival for
      localized cancer ranged from 12.5% to 31.3%, for regional spread 1.3% to 3.4% and
      with distant metastasis not a single site recorded more than 1%. On multivariate
      analysis, extent of disease emerged as an independent predictor of survival with
      all the sites. Also, age for oesophagus, stomach and lung, religion for
      oesophagus and stomach, and education for stomach and lung, emerged as
      independent predictors of survival. CONCLUSION: All the sites included in the
      study demonstrated very low survival rates with significant variation. Comparison
      with other populations revealed lower survival rates than for Shanghai-China. In
      remaining populations, survival proportions did not show much variation for
      pancreas and lung cancers. For stomach cancer, European countries showed better
      survival rates. Early detection with treatment is clearly important to reduce the
      mortality from these cancers.

PMID- 15244522
TI  - Increased risk of endometrial abnormalities in breast cancer patients taking
      tamoxifen: the need for gynaecologic surveillance.
AB  - OBJECTIVE: To evaluate the risk of abnormally thickened endometrium associated
      with tamoxifen treatment in postmenopausal breast cancer patients. METHODS: Two
      groups of asymptomatic postmenopausal breast cancer patients were recruited in
      the study. The first consisted of 70 patients taking 20mg/day of tamoxifen for at
      least 6 months. The second group included 140 patients without tamoxifen
      treatment. Endometrial evaluation using transvaginal ultrasonography (TVS) was
      conducted for all patients. Fractional curettage was carried out for patients
      whose endometrial thickness was greater than 5 mm on TVS. RESULTS: The prevalence
      of abnormally thickened endometrium (greater than 5 mm on TVS) was significantly
      higher in patients receiving tamoxifen (58.57% VS 10.71 %, P = 0.0001). Patients
      undergoing tamoxifen treatment had a 5.61 relative risk of developing abnormally
      thickened endometrium (95% CI= 2.65 -11.86). CONCLUSION: Tamoxifen significantly
      increases the risk of developing abnormally thickened endometrium in
      postmenopausal breast cancer patients. There is, thus, a true need for
      gynaecologic surveillance in such patients to early detect neoplastic change of
      endometrium that may arise as a result of tamoxifen use.

PMID- 15244523
TI  - High frequency of acute promyelocytic leukemia in northwest Iran.
AB  - Acute promyelocytic leukemia (APL) or M3 is a subtype of acute myeloid leukemia,
      according to the French-American-British group classification. High frequencies
      of APL have been reported previously by many investigators. We here studied AML
      patients to determine the frequency of APL in Tabriz in northwest Iran. We
      reviewed 483 AML patients from 1996-2003. M2 and M3 cases accounted for 43.4% and
      19.4% of the total, respectively. Our study thus provides further evidence of
      high frequencies of APL associated with geographical areas. Further studies
      should now be performed to evaluate genetic and environmental predisposing
      factors in Iran.

PMID- 15244524
TI  - Chemomodulatory action of Brassica compestris (var sarason) on hepatic carcinogen
      metabolizing enzymes, antioxidant profiles and lipid peroxidation.
AB  - The effect of two different doses (400 and 800 mg/kg body wt/day for 15 days) of
      a 95% ethanolic extract of the seeds of Brassica compestris (var sarason) was
      examined on carcinogen metabolizing phase-I and phase-II enzymes,antioxidant
      enzymes and glutathione content and lipid peroxidation in the liver of Swiss
      albino mice. Positive control mice were treated with butylated hydroxyanisole
      (BHA). Significant elevation in the levels of cytochrome p450 (p<0,.05),
      cytochrome b5 (p < 0.05) glutathione s-transferase (p<0.01), DT-diaphorase
      (p<0.05), superoxide dismutase (p<0.01), catalase (p < 0.001) and reduced
      glutathione (p<0.001) was noted in the group treated with 800 mg/kg body wt. of
      Brassica extract in comparison with the negative control group. Brassica
      compestris acted as a bifunctional inducer since it induced both phase - I and
      phase - H enzyme systems. Since phase-I and phase-II enzymes are considered to be
      reliable markers for evaluating the chemoprevention efficacy of particular test
      materials,these findings are suggestive of potential chemopreventive roles for
      Brassica seed extract.

PMID- 15244526
TI  - Knowledge about cancer in West Bengal - a pilot survey.
AB  - A pilot survey was conducted based on 900 respondents of the population of West
      Bengal to assess their level of awareness regarding cancer with the aim of
      estimating associations between response variables (knowledge about cancer) and
      predictor variables (age, sex, level of education). The data of the pilot survey
      revealed that 98% of the respondents had heard of the disease 'Cancer'.
      Unfortunately only 35% of the respondents were aware of the 7-danger signals
      (i.e. the primary symptoms of cancer) as defined by the World Health Organisation
      (WHO). None of the respondents knew all 7-primary symptoms of cancer and the
      majority (about 88%) knew only one or two (mainly tumour lumps and ulcers). Only
      44.67% were aware of the major risk factors (like smoking and tobacco chewing).
      The percentage of the respondents believing that most cancers are curable in
      early stages was 58%. Some of the respondents (21%) expressed the vague idea that
      cancer is a infectious disease which is creating a problem of isolation from the
      family/society with some unfortunate cancer patients. Over 11% of the respondents
      suggested that a cancer diagnosis should be kept secret from neighbours due to
      some social stigma like problems with daughters' marriage. Only 8% had
      experienced any cancer awareness programme conducted by any organisation, only
      37% had listened to any cancer awareness programme conducted by the All India
      Radio, only 36% had seen any cancer awareness programme conducted by Doordarsan/
      private Television channels, only 34% had read cancer awareness articles in the
      newspapers/magazines and only 13% had seen posters/hoardings regarding cancer
      awareness. The results thus revealed a huge lack regarding cancer awareness in
      the region. Most of the respondents (68%) expressed a wish for starting cancer
      awareness programmes. From the Pilot Survey it has been found that the average
      Knowledge Index of the respondents is 58+ 1.7 irrespective of the socio-economic
      and personal status. On testing of associations, there was no statistically
      significant association of the Knowledge Index with the domicile status (rural or
      urban), sex, occupation and religion of the respondents. However, statistically
      significant links were evident with the level of education (p=0.00001), social
      participation (p=0.00004) and income (p=0.00013) of the respondents.

PMID- 15244525
TI  - Comparative evaluation of antiproliferative activity and induction of apoptosis
      by some fluoroquinolones with a human non-small cell lung cancer cell line in
      culture.
AB  - Lung cancer is the leading cause of cancer- related death in the world today.
      Since the effective management of drug resistant lung cancer, and particularly
      non-small cell lung carcinomas is a major problem, attempts need to be made to
      identify new potential anticancer drugs that can kill non-small cell lung cancer
      cells efficiently. In the present study, a human non-small cell lung carcinoma
      NCI-H460 cell line was used to evaluate the antiproliferative activity of
      Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin. As
      determined by Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused
      cellular growth inhibition in a concentration and time-dependent manner. Enoxacin
      was found to be the most effective Fluoroquinolone followed by Norfloxacin,
      Ciprofloxacin and Levofloxacin. Growth inhibitory effects were also found to be
      independent of the concentrations of serum growth factors in culture medium or
      variation of initial cell seeding density and proved to be irreversible in
      nature. Appearance of rounded cells with altered morphology and cell surface
      blebbing indicated cell killing by apoptosis. Cell shrinkage, nuclear
      condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG
      staining confirmed this to be the case. Thus, this investigation clearly
      demonstrated that the NCI-H460 human non-small cell lung carcinoma cell line is
      highly sensitive to Fluoroquinolone treatment. The Fluoroquinolones used in this
      study which are clinically used as antibacterial agents, can also inhibit tumor
      cell growth suggesting their potential use in a strategy for cancer treatment
      which might help in controlling cancer.

PMID- 15244527
TI  - Knowledge and concerns about cancer in patients with primary gynecologic cancers.
AB  - OBJECTIVE: The aim of this study was to measure the level of knowledge about
      cancer among patients with primary gynecologic cancers and the rate of awareness
      for diagnosis. METHODS: Two hundred patients with primary gynecologic cancers in
      Vaie Asr & Mirza Kochak Khan hospitals, Tehran/Iran, participated and entered the
      study and were interviewed by trained nurses. The interview included questions
      about knowledge of their cancer and risk factors. RESULTS: One hundred fifteen of
      200 subjects (58%) knew that their disease was malignant, of which 56 were aware
      of the exact diagnosis. Fifty six percent of the subjects believed that doctors
      must say the true diagnosis. The level of general knowledge about cancer was poor
      in 34%of cases. Regarding cancer risk factors, 47% had a poor level of knowledge.
      Misconception about injury and depression as predisposing factors were common.
      Level of general knowledge was significantly higher in younger than in older
      patients (p<0.05). Also patients with a greater length of formal education had a
      higher level of knowledge (p<0.0001). Patients who received information from
      medical personnel and who were aware of diagnosis had a higher level of knowledge
      (p<0.0001). CONCLUSION: The level of knowledge about cancer should be promoted in
      both the general public and in patients. Medical personnel may play a great role
      in this field.

PMID- 15244528
TI  - Ethnic and age variation of cancer of the reproductive system in women of
      Kyrgyzstan.
AB  - The purpose of this research was to assess the ethnic and age variation in the
      incidence rates of cancer of the female reproductive system (cancers of the
      breast, cervix uteri, corpus uteri and ovaries) in Kyrgyzstan. A retrospective
      approach was adopted covering the period from 1995 to 2002 with descriptive and
      analytical methods to estimated incidence rates in women of Russian and Kyrgyz
      nationalities. Values were found to be higher in Russian women but decreasing
      over time, while increase was observed for the Kyrgyz. Breast cancers were most
      common in Russian women and in their Kyrgyz counterparts cancer of the cervix
      uteri predominated. The data reveal age and ethnic variation in cancer
      localization.

PMID- 15244529
TI  - Breast cancer in Iran: a survival analysis.
AB  - A prospective study was undertaken to examine survival in Iranian breast cancer
      patients. One hundred and sixty-seven breast cancer patients diagnosed in 1997
      were entered into the study and followed up for five years. The mean age of the
      patients at diagnosis was 47.2 (SD = 13.5), ranging from 24 to 81 years. A total
      of 39 patients were lost in the follow-up period, leaving 128 for analysis of
      data. Of these, 79 were alive and 49 were dead after five years. Most patients
      (61%) presented with advanced disease. Using life table analysis, the overall
      relative 5-year survival rate was found to be 62% (SE = 0.04). In addition, after
      adjustment for age at diagnosis, initial treatment (mastectomy, breast conserving
      surgery, and neo-adjuvant therapy), and disease stage, using Cox's regression
      model, it was found that receiving neo-adjuvant therapy as the initial treatment
      was an independent predictor of poorer survival (Hazard ratio = 4.56, 95% CI 2.20
      9.44, P<0.0001). The other variables (older age and late stage disease), although
      associated with high hazards rates, were not significant. The study findings
      suggest that overall relative survival rate in Iranian breast cancer patients
      stands between western and eastern European countries and needs to be improved.
      It seems that early detection and better management using standard guidelines
      might contribute considerably to improvement of survival in women experiencing
      breast cancer.

PMID- 15244531
TI  - Hybrid method for simulating front propagation in reaction-diffusion systems.
AB  - We study the propagation of pulled fronts in the A<--> A+A microscopic reaction
      diffusion process using Monte Carlo simulations. In the mean field approximation
      the process is described by the deterministic Fisher-Kolmogorov-Petrovsky
      Piscounov equation. In particular, we concentrate on the corrections to the
      deterministic behavior due to the number of particles per correlated volume
      Omega. By means of a hybrid simulation scheme, we manage to reach large
      macroscopic values of Omega, which allows us to show the importance in the
      dynamics of microscopic pulled fronts of the interplay of microscopic
      fluctuations and their macroscopic relaxation.

PMID- 15244530
TI  - Improving cancer care in India: prospects and challenges.
AB  - The World Cancer Report, a 351 - page global report issued by International
      Agency for Research on Cancer (IARC) tells us that cancer rates are set to
      increase at an alarming rate globally (Stewart and Kleiues 2003). Cancer rates
      could increase by 50 % to 15 million new cases in the year 2020. This will be
      mainly due to steadily aging populations in both developed and developing
      countries and also to current trends in smoking prevalence and the growing
      adoption of unhealthy lifestyles. The report also reveals that cancer has emerged
      as a major public health problem in developing countries, matching its effect in
      industrialized nations. Healthy lifestyles and public health action by
      governments and health practitioners could stem this trend, and prevent as many
      as one third of cancers worldwide. In a developing country such as India there
      has been a steady increase in the Crude Incidence Rate (CIR) of all cancers
      affecting both men and women over the last 15 years. The increase reported by the
      cancer registries is nearly 12 per cent from 1985 to 2001, representing a 57 per
      cent rise in India's cancer burden. The total number of new cases, which stood at
      5.3 lakhs Care lakh is 100,000 in 1985 has risen to over 8.3 lakhs today. The
      pattern of cancers has changed over the years, with a disturbing increase in
      cases that are linked to the use of tobacco. In 2003, there were 3.85 lakhs of
      cases coming under this category in comparison with 1.94 lakhs cases two decades
      ago. Lung cancer is now the second most common cancer among men. Earlier, it was
      in fifth place. Among women in urban areas, cancer of the uterine cervix had the
      highest incidence 15 years ago, but it has now been overtaken by breast cancer.
      In rural areas, cervical cancer remains the most common form of the disease (The
      Hindu 2004).

PMID- 15244532
TI  - Electrostatic attraction between neutral microdroplets by ion fluctuations.
AB  - The interaction between two aqueous droplets containing ions is investigated. The
      ion-fluctuation correlation gives rise to attraction between two neutral
      microdroplets, similar to the van der Waals interaction between neutral atoms.
      Electrostatic attraction consists of contributions from various induced multipole
      multipole interactions, including dipole-dipole < P(2)(z) >(2) r(-6), dipole
      quadrupole < P(2)(z) > < Q (2)(zz ) > r(-8), dipole-octupole < P(2)(z) > < O
      (2)(zzz ) > r(-10), and quadrupole-quadrupole interactions < Q (2)(zz ) >(2) r(
      10). The mean-square multipole moments are determined analytically by linear
      response theory. The fluctuation-driven attraction is so strong at short distance
      that it may dominate over the Coulomb repulsion between like-charged droplets.
      These theoretical results are confirmed by Monte Carlo simulations.

PMID- 15244533
TI  - Self-assembled uniaxial and biaxial multilayer structures in chiral smectic
      liquid crystals frustrated between ferro- and antiferroelectricity.
AB  - With a view to obtain a molecular model for the subphases produced by the
      frustration between ferro- and antiferroelectricity in chiral smectic liquid
      crystals, we report results on two compounds and observe (i) the staircase
      character of uniaxial Sm C(*)(alpha) itself in the bulk and (ii) the multipeaked
      characteristic reflection bands due to the modulated helical structures just
      above the Sm C(*)(A) temperature range. We suggest the emergence of several
      uniaxial and biaxial subphases. The results show that both types of subphases can
      be specified by q(T) = [F] / ( [A] + [F] ) in the zero-order approximation; [A]
      and [F] are the numbers of antiferroelectric and ferroelectric orderings in the
      unit cell. We consider the basis of both types of subphases, particularly the
      description of the short-pitch helical structure of Sm C(*)(alpha), in terms of
      the molecular models so far proposed and emphasize the important role played by
      the discrete flexoelectric polarization.

PMID- 15244534
TI  - Partition function, metastability, and kinetics of the escape transition for an
      ideal chain.
AB  - An end-tethered polymer chain squeezed between two pistons undergoes an abrupt
      transition from a confined coil state to an inhomogeneous flower-like
      conformation partially escaped from the gap. We present a rigorous analytical
      theory for the equilibrium and kinetic aspects of this phenomenon for a Gaussian
      chain. Applying the analogy with the problem of the adsorption of an ideal chain
      constrained by one of its ends, we obtain a closed analytical expression for the
      exact partition function. Various equilibrium thermodynamic characteristics (the
      fraction of imprisoned segments, the average compression, and lateral forces) are
      calculated as a function of the piston separation. The force versus separation
      curve is studied in two complementary statistical ensembles, the constant force
      and the constant confinement width ones. The differences in these force curves
      are significant in the transition region for large systems, but disappear for
      small systems. The effects of metastability are analyzed by introducing the
      Landau free energy as a function of the chain stretching, which serves as the
      order parameter. The phase diagram showing the binodal and two spinodal lines is
      presented. We obtain the barrier heights between the stable and metastable states
      in the free energy landscape. The mean first passage time, i.e., the lifetime of
      the metastable coil and flower states, is estimated on the basis of the Fokker
      Planck formalism. Equilibrium analytical theory for a Gaussian chain is
      complemented by numerical calculations for a lattice freely jointed chain model.

PMID- 15244535
TI  - Scaling and crossovers in activated escape near a bifurcation point.
AB  - Near a bifurcation point a system experiences a critical slowdown. This leads to
      scaling behavior of fluctuations. We find that a periodically driven system may
      display three scaling regimes and scaling crossovers near a saddle-node
      bifurcation where a metastable state disappears. The rate of activated escape W
      scales with the driving field amplitude A as ln W proportional, variant ( A(c) 
      A)(xi), where A(c) is the bifurcational value of A. With increasing field
      frequency the critical exponent xi changes from xi=3/2 for stationary systems to
      a dynamical value xi=2 and then again to xi=3/2. The analytical results are in
      agreement with the results of asymptotic calculations in the scaling region.
      Numerical calculations and simulations for a model system support the theory.

PMID- 15244536
TI  - Noise-enhanced stability in fluctuating metastable states.
AB  - We derive general equations for the nonlinear relaxation time of Brownian
      diffusion in randomly switching potential with a sink. For piece-wise linear
      dichotomously fluctuating potential with metastable state, we obtain the exact
      average lifetime as a function of the potential parameters and the noise
      intensity. Our result is valid for arbitrary white noise intensity and for
      arbitrary fluctuation rate of the potential. We find noise enhanced stability
      phenomenon in the system investigated: The average lifetime of the metastable
      state is greater than the time obtained in the absence of additive white noise.
      We obtain the parameter region of the fluctuating potential where the effect can
      be observed. The system investigated also exhibits a maximum of the lifetime as a
      function of the fluctuation rate of the potential.

PMID- 15244537
TI  - Analytical results for fundamental time-delayed feedback systems subjected to
      multiplicative noise.
AB  - We study the stochastic behavior of fundamental time-delayed feedback systems
      subjected to multiplicative noise. We derive exact results for the first and
      second moments and the autocorrelation function. For a particular class of
      systems we show how the variance depends on the amplitude of the multiplicative
      noise. Furthermore, we identify parameter regions of stationary solutions with
      finite and infinite variances. Finally, we suggest that delay-induced Levy
      flights may occur in time-delayed feedback systems involving multiplicative
      noise.

PMID- 15244538
TI  - Ornstein-Zernike equation and Percus-Yevick theory for molecular crystals.
AB  - We derive the Ornstein-Zernike equation for molecular crystals of axially
      symmetric particles and apply the Percus-Yevick approximation. The one-particle
      orientational distribution function rho((1)) (Omega) has a nontrivial dependence
      on the orientation Omega, in contrast to a liquid, and is needed as an input.
      Despite some differences, the Ornstein-Zernike equation for molecular crystals
      has a similar structure as for liquids. We solve both equations numerically for
      hard ellipsoids of revolution on a simple cubic lattice. Compared to molecular
      liquids, the orientational correlators in direct and reciprocal space exhibit
      less structure. However, depending on the lengths a and b of the rotation axis
      and the perpendicular axes of the ellipsoids, respectively, different behavior is
      found. For oblate and prolate ellipsoids with b greater, similar 0.35 (in units
      of the lattice constant), damped oscillations in distinct directions of direct
      space occur for some of the orientational correlators. They manifest themselves
      in some of the correlators in reciprocal space as a maximum at the Brillouin zone
      edge, accompanied by a maximum at the zone center for other correlators. The
      oscillations indicate alternating orientational fluctuations, while the maxima at
      the zone center originate from ferrorotational fluctuations. For a less, similar
      2.5 and b less, similar 0.35, the oscillations are weaker, leading to no marked
      maxima at the Brillouin zone edge. For a greater, similar 3.0 and b less, similar
      0.35, no oscillations occur any longer. For many of the orientational correlators
      in reciprocal space, an increase of a at fixed b or vice versa leads to a
      divergence at the zone center q=0, consistent with the formation of
      ferrorotational long-range fluctuations, and for some oblate and prolate systems
      with b less, similar 1.0 a simultaneous tendency to divergence of few other
      correlators at the zone edge is observed. Comparison of the orientational
      correlators with those from Monte Carlo simulations shows satisfactory agreement.
      From these simulations we also obtain a phase boundary in the a-b plane for order
      disorder transitions.

PMID- 15244539
TI  - Colored-noise-induced discontinuous transitions in symbiotic ecosystems.
AB  - A symbiotic ecosystem is studied by means of the Lotka-Volterra stochastic model,
      using the generalized Verhulst self-regulation. The effect of fluctuating
      environment on the carrying capacity of a population is taken into account as
      dichotomous noise. The study is a follow-up of our investigation of symbiotic
      ecosystems subjected to three-level (trichotomous) noise [Phys. Rev. E 65, 051108
      (2002)]]. Relying on the mean-field theory, an exact self-consistency equation
      for stationary states is derived. In some cases the mean field exhibits
      hysteresis as a function of noise parameters. It is established that random
      interactions with the environment can cause discontinuous transitions. The
      dependence of the critical coupling strengths on the noise parameters is found
      and illustrated by phase diagrams. Predictions from the mean-field theory are
      compared with the results of numerical simulations. Our results provide a
      possible scenario for catastrophic shifts of population sizes observed in nature.

PMID- 15244540
TI  - Broad relaxation spectrum and the field theory of glassy dynamics for pinned
      elastic systems.
AB  - We study thermally activated, low-temperature equilibrium dynamics of elastic
      systems pinned by disorder using one loop functional renormalization group (FRG).
      Through a series of increasingly complete approximations, we investigate how the
      field theory reveals the glassy nature of the dynamics, in particular divergent
      barriers and barrier distributions controling the spectrum of relaxation times.
      First, we naively assume a single relaxation time tau(k) for each wave vector k,
      leading to analytical expressions for equilibrium dynamical response and
      correlations. These exhibit two distinct scaling regimes (scaling variables T
      k(theta) ln t and t/ tau(k), respectively, with T the temperature, theta the
      energy fluctuation exponent, and tau(k) approximately e(c k(-theta) /T) ) and are
      easily extended to quasiequilibrium and aging regimes. A careful study of the
      dynamical operators encoding for fluctuations of the relaxation times shows that
      this first approach is unsatisfactory. A second stage of approximation including
      these fluctuations, based on a truncation of the dynamical effective action to a
      random friction model, yields a size (L) dependent log-normal distribution of
      relaxation times (effective barriers centered around Ltheta and of fluctuations
      approximately L(theta/2) ) and some procedure to estimate dynamical scaling
      functions. Finally, we study the full structure of the running dynamical
      effective action within the field theory. We find that relaxation time
      distributions are nontrivial (broad but not log normal) and encoded in a closed
      hierarchy of FRG equations divided into levels p=0,1, em leader, corresponding to
      vertices proportional to the pth power of frequency omega(p). We show how each
      level p can be solved independently of higher ones, the lowest one (p=0)
      comprising the statics. A thermal boundary layer ansatz (TBLA) appears as a
      consistent solution. It extends the one discovered in the statics which was shown
      to embody droplet thermal fluctuations. Although perturbative control remains a
      challenge, the structure of the dynamical TBLA which encodes barrier
      distributions opens the way for deeper understanding of the field theory approach
      to glasses.

PMID- 15244541
TI  - Scaling and universality of inherent structure simulations.
AB  - In this paper we explore the inherent structures (IS) approach to the dynamics of
      the East constrained kinetic Ising model. The inherent structures do not capture
      the nature of the dynamics of many quantities, including the spin autocorrelation
      function. Simply monitoring the quenched energy fluctuations, i.e., IS energy,
      results in an oversimplified single order-parameter description of the system's
      dynamics, but examining other features, such as domain dynamics or normal modes,
      may give a more complete and useful picture of the dynamics. The universality in
      the behavior of the IS energy of this model does not reveal nonuniversal features
      of the kinetics that determine long-time relaxation of the system. As a result,
      popular functional forms, such as the stretched exponential relaxation or
      Gaussian distribution of energies, may be a numerical fit to data with little
      physical justification. Filtering data can be shown to erase features of the
      system and the resulting quantities resemble more universal functional forms that
      lack physical insight. These results for the East model have implications for IS
      simulations of realistic systems and suggest careful analysis including the
      examination of other potential order parameters is necessary to evaluate the
      validity of applications of universal and scaling arguments to IS simulations.

PMID- 15244542
TI  - Bethe ansatz solution of zero-range process with nonuniform stationary state.
AB  - The eigenfunctions and eigenvalues of the master equation for zero-range process
      with totally asymmetric dynamics on a ring are found exactly using the Bethe
      ansatz weighted with the stationary weights of particle configurations. The Bethe
      ansatz applicability requires the rates of hopping of particles out of a site to
      be the q numbers [n](q). This is a generalization of the rates of hopping of
      noninteracting particles equal to the occupation number n of a site of departure.
      The noninteracting case can be restored in the limit q-->1. The limiting cases of
      the model for q=0, infinity correspond to the totally asymmetric exclusion
      process, and the drop-push model, respectively. We analyze the partition function
      of the model and apply the Bethe ansatz to evaluate the generating function of
      the total distance traveled by particles at large time in the scaling limit. In
      case of nonzero interaction, q not equal 1, the generating function has the
      universal scaling form specific for the Kardar-Parizi-Zhang universality class.

PMID- 15244543
TI  - Comparison of aperiodic stochastic resonance in a bistable system realized by
      adding noise and by tuning system parameters.
AB  - Two methods of realizing aperiodic stochastic resonance (ASR) by adding noise and
      tuning system parameters in a bistable system, after a scale transformation, can
      be compared in a real parameter space. In this space, the resonance point of ASR
      via adding noise denotes the extremum of a line segment, whereas the method of
      tuning system parameters presents the extrema of a parameter plane. We
      demonstrate that, in terms of the system performance, the method of tuning system
      parameters takes the precedence of the approach of adding noise for an adjustable
      bistable system. Besides, adding noise can be viewed as a specific case of tuning
      system parameters. Further research shows that the optimal system found by tuning
      system parameters may be subthreshold or suprathreshold, and the conventional ASR
      effects might not occur in some suprathreshold optimal systems.

PMID- 15244544
TI  - Self-diffusion in a system of interacting Langevin particles.
AB  - The behavior of the self-diffusion constant of Langevin particles interacting via
      a pairwise interaction is considered. The diffusion constant is calculated
      approximately within a perturbation theory in the potential strength about the
      bare diffusion constant. It is shown how this expansion leads to a systematic
      double expansion in the inverse temperature beta and the particle density rho.
      The one-loop diagrams in this expansion can be summed exactly and we show that
      this result is exact in the limit of small beta and rhobeta constants. The one
      loop result can also be resummed using a semiphenomenological renormalization
      group method which has proved useful in the study of diffusion in random media.
      In certain cases the renormalization group calculation predicts the existence of
      a diverging relaxation time signaled by the vanishing of the diffusion constant,
      possible forms of divergence coming from this approximation are discussed.
      Finally, at a more quantitative level, the results are compared with numerical
      simulations, in two dimensions, of particles interacting via a soft potential
      recently used to model the interaction between coiled polymers.

PMID- 15244545
TI  - Directed polymers and interfaces in random media: free-energy optimization via
      confinement in a wandering tube.
AB  - We analyze, via Imry-Ma scaling arguments, the strong disorder phases that exist
      in low dimensions at all temperatures for directed polymers and interfaces in
      random media. For the uncorrelated Gaussian disorder, we obtain that the optimal
      strategy for the polymer in dimension 1+d with 0<d<2 involves at the same time
      (i) a confinement in a favorable tube of radius R(S) approximately L (nu(S) )
      with nu(S) =1/(4-d)<1/2 (ii) a superdiffusive behavior R approximately Lnu with
      nu=(3-d)/(4-d)>1/2 for the wandering of the best favorable tube available. The
      corresponding free energy then scales as F approximately Lomega with omega=2nu-1
      and the left tail of the probability distribution involves a stretched
      exponential of exponent eta=(4-d)/2. These results generalize the well known
      exact exponents nu=2/3, omega=1/3, and eta=3/2 in d=1, where the subleading
      transverse length R(S) approximately L(1/3) is known as the typical distance
      between two replicas in the Bethe ansatz wave function. We then extend our
      approach to correlated disorder in transverse directions with exponent alpha
      and/or to manifolds in dimension D+d= d(t) with 0<D<2. The strategy of being both
      confined and superdiffusive is still optimal for decaying correlations ( alpha<0
      ), whereas it is not for growing correlations ( alpha>0 ). In particular, for an
      interface of dimension ( d(t) -1) in a space of total dimension 5/3< d(t) <3 with
      random-bond disorder, our approach yields the confinement exponent nu(S) =( d(t) 
      1)(3- d(t) )/(5 d(t) -7). Finally, we study the exponents in the presence of an
      algebraic tail 1/ V1+micro in the disorder distribution, and obtain various
      regimes in the (micro,d) plane.

PMID- 15244546
TI  - Calculations of free energies in liquid and solid phases: fundamental measure
      density-functional approach.
AB  - In this paper, a theoretical description of the free energies and correlation
      functions of hard-sphere (HS) liquid and solid phases is developed using
      fundamental measure density-functional theory. Within the framework of Weeks
      Chandler-Andersen perturbation theory, free energies of liquid and solid phases
      with many interaction potentials can be obtained from these characteristics of
      the HS system within a single theoretical description. An application to the
      Lennard-Jones system yields liquid-solid coexistence results in good agreement
      with the ones from simulations.

PMID- 15244547
TI  - Stationary Kolmogorov solutions of the Smoluchowski aggregation equation with a
      source term.
AB  - In this paper we show how the method of Zakharov transformations may be used to
      analyze the stationary solutions of the Smoluchowski aggregation equation with a
      source term for arbitrary homogeneous coagulation kernel. The resulting power-law
      mass distributions are of Kolmogorov type in the sense that they carry a constant
      flux of mass from small masses to large. They are valid for masses much larger
      than the characteristic mass of the source. We derive a "locality criterion,"
      expressed in terms of the asymptotic properties of the kernel, that must be
      satisfied in order for the Kolmogorov spectrum to be an admissible solution.
      Whether a given kernel leads to a gelation transition or not can be determined by
      computing the mass capacity of the Kolmogorov spectrum. As an example, we compute
      the exact stationary state for the family of kernels, K(zeta) ( m(1), m(2) )= (
      m(1) m(2) )(zeta/2) which includes both gelling and nongelling cases, reproducing
      the known solution in the case zeta=0. Surprisingly, the Kolmogorov constant is
      the same for all kernels in this family.

PMID- 15244548
TI  - Heat transfer in the Knudsen layer.
AB  - A concept of the surface heat conductivity determining a heat transfer in the
      Knudsen layer was introduced. It has the same order with respect to the Knudsen
      number as the bulk heat transfer and must be taken into account in practical
      calculations. Using the Onsager principle the coefficient of the surface heat
      conductivity was related to the thermal slip coefficient.

PMID- 15244549
TI  - Replica Ornstein-Zernike self-consistent theory for mixtures in random pores.
AB  - We present a self-consistent integral equation theory for a binary liquid in
      equilibrium with a disordered medium, based on the formalism of the replica
      Ornstein-Zernike (ROZ) equations. Specifically, we derive direct formulas for the
      chemical potentials and the zero-separation theorems (the latter provide a
      connection between the chemical potentials and the fluid cavity distribution
      functions). Next we solve a modified-Verlet closure to ROZ equations, which has
      built-in parameters that can be adjusted to satisfy the zero-separation theorems.
      The degree of thermodynamic consistency of the theory is also kept under control.
      We model the binary fluid in random pores as a symmetrical binary mixture of
      nonadditive hard spheres in a disordered hard-sphere matrix and consider two
      different values of the nonadditivity parameter and of the quenched matrix
      packing fraction, at different mixture concentrations. We compare the theoretical
      structural properties as obtained through the present approach with Percus-Yevick
      and Martinov-Sarkisov integral equation theories, and assess both structural and
      thermodynamic properties by performing canonical standard and biased grand
      canonical Monte Carlo simulations. Our theory appears superior to the other
      integral equation schemes here examined and provides reliable estimates of the
      chemical potentials. This feature should be useful in studying the fluid phase
      behavior of model adsorbates in random pores in general.

PMID- 15244550
TI  - Brillouin neutron scattering in heavy water: evidence for two-mode collective
      dynamics.
AB  - A high resolution (1.5 meV) inelastic neutron scattering experiment was carried
      out, aiming at an accurate investigation of the high frequency and low momentum
      dynamic response in heavy water. The experimental data confirm the existence of a
      dispersionless mode, besides the ordinary longitudinal collective dynamics. A
      simplified model, based on the interaction of two vibrational branches, is
      proposed to interpret the observed features of the dynamic spectra. The validity
      extent of this scheme is proved by applying it to room temperature neutron and x
      ray data, to temperature and pressure dependent x-ray data, and to room
      temperature neutron data of vibrational density of states. The overall
      successfull results provided by this model, in conjunction with the combined
      analysis of the x-ray and neutron data on collective dynamics, enable a deeper
      insight into the complex mechanisms of the water dynamics and provide a simple
      phenomenological explanation for the transition from ordinary to fast sound.

PMID- 15244551
TI  - Reaction ensemble Monte Carlo technique and hypernetted chain approximation study
      of dense hydrogen.
AB  - In spite of the simple structure of hydrogen, up to now there is no unified
      theoretical and experimental description of hydrogen at high pressures. Recent
      results of Z-pinch experiments show a large deviation from those obtained by
      laser driven ones. Theoretical investigations including ab initio computer
      simulations show considerable differences at such extreme conditions from each
      other and from experimental values. We apply the reaction ensemble Monte Carlo
      technique on one hand and a combination of the hypernetted chain approximation
      with the mass action law on the other to study the behavior of dense hydrogen at
      such conditions. The agreement between both methods for the equation of state and
      for the Hugoniot curve is excellent. Comparison to other methods and experimental
      results is also performed.

PMID- 15244552
TI  - Excitation lines and the breakdown of Stokes-Einstein relations in supercooled
      liquids.
AB  - By applying the concept of dynamical facilitation and analyzing the excitation
      lines that result from this facilitation, we investigate the origin of decoupling
      of transport coefficients in supercooled liquids. We illustrate our approach with
      two classes of models. One depicts diffusion in a strong glass former, and the
      other in a fragile glass former. At low temperatures, both models exhibit
      violation of the Stokes-Einstein relation, D approximately tau(-1), where D is
      the self-diffusion constant and tau is the structural relaxation time. In the
      strong case, the violation is sensitive to dimensionality d, going as D
      approximately tau(-2/3) for d=1 and as D approximately tau(-0.95) for d=3. In the
      fragile case, however, we argue that dimensionality dependence is weak, and show
      that for d=1, D approximately tau(-0.73). This scaling for the fragile case
      compares favorably with the results of a recent experimental study for a three
      dimensional fragile glass former.

PMID- 15244553
TI  - Liquid-liquid phase transitions for soft-core attractive potentials.
AB  - Using event-driven molecular dynamics simulations, we study a three-dimensional
      one-component system of spherical particles interacting via a discontinuous
      potential combining a repulsive square soft core and an attractive square well.
      In the case of a narrow attractive well, it has been shown that this potential
      has two metastable gas-liquid critical points. Here we systematically investigate
      how the changes of the parameters of this potential affect the phase diagram of
      the system. We find a broad range of potential parameters for which the system
      has both a gas-liquid critical point C1 and a liquid-liquid critical point C2.
      For the liquid-gas critical point we find that the derivatives of the critical
      temperature and pressure, with respect to the parameters of the potential, have
      the same signs: they are positive for increasing width of the attractive well and
      negative for increasing width and repulsive energy of the soft core. This result
      resembles the behavior of the liquid-gas critical point for standard liquids. In
      contrast, for the liquid-liquid critical point the critical pressure decreases as
      the critical temperature increases. As a consequence, the liquid-liquid critical
      point exists at positive pressures only in a finite range of parameters. We
      present a modified van der Waals equation which qualitatively reproduces the
      behavior of both critical points within some range of parameters, and gives us
      insight on the mechanisms ruling the dependence of the two critical points on the
      potential's parameters. The soft-core potential studied here resembles model
      potentials used for colloids, proteins, and potentials that have been related to
      liquid metals, raising an interesting possibility that a liquid-liquid phase
      transition may be present in some systems where it has not yet been observed.

PMID- 15244554
TI  - Velocity distribution for a two-dimensional sheared granular flow.
AB  - The velocity distribution for a two-dimensional collection of disks of number
      density n per unit area and radius a in a channel of width L is studied. The
      particle-particle collisions are considered to be inelastic with a coefficient of
      restitution e, while the particle-wall coefficients of restitution are inelastic
      with a tangential and normal coefficients of restitution, e(t) and e(n),
      respectively. The Knudsen number, which is the ratio of the channel width and the
      mean free path of the particles, is varied from Kn<<1 to Kn>>1. In the limit of
      high Knudsen number, the distribution function for the streamwise velocity is
      bimodal, as predicted by theory [J. Fluid Mech. 340, 3l9 (1997)]], and the
      scalings of the moments of the velocity distribution with the Knudsen number are
      in agreement with the theory. In the low Knudsen number limit, the distribution
      function for the streamwise velocity is a Gaussian if the coefficient of
      restitution is close to 1, but assumes the form of a "composite Gaussian" if the
      coefficient of restitution is not close to 1. The distribution function has a
      complex structure in the intermediate regime, where there are three maxima in the
      distribution function near the wall, while the distribution function is bimodal
      at the center. The granular temperature is accurately predicted by kinetic theory
      at the center of the channel, but there is dissipation at the wall due to
      inelastic particle-wall collisions, which results in a significant decrease in
      the temperature even when the coefficient of restitution is 0.9; this finding is
      in agreement with previous results with bumpy wall boundary conditions and with
      specular reflection conditions. The slip velocity at the wall has a power law
      dependence on the Knudsen number, and the exponent in this power law depends on
      the coefficients of restitution.

PMID- 15244555
TI  - Cohesion induced by a rotating magnetic field in a granular material.
AB  - We report experiments on a magnetic cohesive granular material made of steel
      spheres in the millimeter range. A magnetic field magnetizes the spheres, so that
      an interaction force between grains appears. A rotating magnetic field is applied
      parallel to plane of the quasi-two-dimensional cell containing the spheres so
      that only the time averaged force between two particles will be considered. Both
      maximum angle of stability and angles of repose are measured. The maximum angle
      of stability is found to depend linearly on the interaction force. Another
      noticeable feature is the lack of dependence of the maximum angle of stability on
      the initial height of the heap. We show that the angle of repose is less
      sensitive to the magnetic interaction force than the maximum of stability. At
      last, we discuss the importance of using a rotating field rather than a constant
      one. In particular, we report some measurements of both the maximum angle of
      stability and the angle of repose in constant field, which show a strong
      dependence of the angles of avalanche on the direction of the field.

PMID- 15244556
TI  - Inherent rheology of a granular fluid in uniform shear flow.
AB  - In contrast to normal fluids, a granular fluid under shear supports a steady
      state with uniform temperature and density since the collisional cooling can
      compensate locally for viscous heating. It is shown that the hydrodynamic
      description of this steady state is inherently non-Newtonian. As a consequence,
      the Newtonian shear viscosity cannot be determined from experiments or simulation
      of uniform shear flow. For a given degree of inelasticity, the complete nonlinear
      dependence of the shear viscosity on the shear rate requires the analysis of the
      unsteady hydrodynamic behavior. The relationship to the Chapman-Enskog method to
      derive hydrodynamics is clarified using an approximate Grad's solution of the
      Boltzmann kinetic equation.

PMID- 15244557
TI  - Thermal convection in monodisperse and bidisperse granular gases: a simulation
      study.
AB  - We present results of a simulation study of inelastic hard disks vibrated in a
      vertical container. An event-driven molecular dynamics method is developed for
      studying the onset of convection. Varying the relevant parameters (inelasticity,
      number of layers at rest, intensity of the gravity) we are able to obtain a
      qualitative agreement of our results with recent hydrodynamical predictions.
      Increasing the inelasticity, a first continuous transition from the absence of
      convection to one convective roll is observed, followed by a discontinuous
      transition to two convective rolls, with hysteretic behavior. At fixed
      inelasticity and increasing gravity, a transition from no convection to one roll
      can be evidenced. If the gravity is further increased, the roll is eventually
      suppressed. Increasing the number of monolayers the system eventually localizes
      mostly at the bottom of the box: in this case multiple convective rolls as well
      as surface waves appear. We analyze the density and temperature fields and study
      the existence of symmetry breaking in these fields in the direction perpendicular
      to the injection of energy. We also study a binary mixture of grains with
      different properties (inelasticity or diameters). The effect of changing the
      properties of one of the components is analyzed, together with density,
      temperature, and temperature ratio fields. Finally, the presence of a low
      fraction of quasielastic impurities is shown to determine a sharp transition
      between convective and nonconvective steady states.

PMID- 15244558
TI  - Granular systems on a vibrating wall: the kinetic boundary condition.
AB  - Dense granular media, fluidized by a vibrating wall, is studied in the high
      vibrating frequency limit, where the plate vibration frequency is much greater
      than the collision frequency, and the plate acceleration is much greater than
      gravity. Using kinetic theory, it is shown that, regardless of the fluid density,
      external field, or restitution coefficient between particles, there is an
      asymptotic scaling for saying that if Aomega is kept constant, then different
      amplitudes A (with the corresponding frequencies omega ) produce the same
      macroscopic result. Furthermore, it is found that in the limit of high
      frequencies, the boundary condition associated with the vibrating wall can be
      replaced by a stationary heat source. The value of the heat flux depends linearly
      with density even for dense fluids. Numerical comparisons with molecular dynamics
      simulations confirm these predictions and show that the substitution of the
      vibrating wall by a thermal one gives poor results, while the substitution by a
      heat source is very accurate.

PMID- 15244559
TI  - Slow drag in granular materials under high pressure.
AB  - The resistance offered by a cylindrical rod to creeping cross flow of granular
      materials under pressure is investigated. The experimental system consists of a
      confined bed of granular particles, which are compacted under high pressure to
      consolidate the granular medium. A cylindrical rod is pulled at a constant and
      slow rate through the granular medium, and the measured pulling resistance is
      characterized as a drag force. The influence of various parameters such as the
      velocity of the cylindrical rod, the rod diameter and length, the granular
      particle size, and the compaction pressure on the required drag force is
      investigated experimentally. Nondimensional analysis is performed to simplify the
      relationships between these variables. The results show that the drag force is
      independent of the drag velocity, is linearly proportional to compaction pressure
      and rod diameter, and increases with rod length and particle size. Additional
      compaction experiments show that the effective density of the granular bed
      increases linearly with pressure, and similar behavior is noted for all particle
      sizes. These results should prove useful in the development of constitutive
      equations that can describe the motion of solid objects through compacted
      granular media under high pressure, such as during ballistic penetration of soils
      or ceramic armors.

PMID- 15244560
TI  - Fluctuations of the solid discharge of gravity-driven particle flows in a
      turbulent stream.
AB  - Substantial variations in the particle flux are commonly observed in field
      measurements on gravel-bed rivers and in laboratory experiments mimicking river
      behavior on a smaller scale. These fluctuations can be explained by the natural
      variability of sediment supply and hydraulic conditions. We conducted laboratory
      experiments of particle transport down a two-dimensional inclined channel, for
      which the boundary conditions were properly controlled. Most flow variables and
      the features of particle trajectories were measured using a high-speed camera.
      The particles were 6-mm glass beads entrained by a rapid, turbulent,
      supercritical water flow. Even under these well-controlled experimental
      conditions and despite steady supply, solid discharge exhibited significant
      variations with time. The objective of this paper was to pinpoint the origins of
      these fluctuations by investigating different flow conditions. Two experiments
      were done with a fixed (smooth or corrugated) channel bottom and two others were
      run with a mobile bed (involving layers of closely packed particles lying along
      the channel base, which could be entrained by the stream); in the latter case,
      two particle arrangements were tested. It was found that, to a large extent,
      fluctuations reflected the finite size of the observation window. For fixed beds,
      the characteristic time scale of fluctuations and their probability distribution
      can be predetermined by evaluating the mean and fluctuating velocities of a
      single particle. Solid-discharge fluctuations were exacerbated when the bed was
      mobile because (i) the moving solid phase and the stationary bed exchanged
      particles and (ii) collective entrainment of particles occurred.

PMID- 15244561
TI  - Anisotropic energy distribution in three-dimensional vibrofluidized granular
      systems.
AB  - We examine the energy flows in a three-dimensional model of a granular system
      consisting of N inelastic hard spheres contained in an open cylinder of radius R
      under the influence of gravity. Energy is supplied to the system in the vertical
      direction by a vibrating base and is transferred to the perpendicular directions
      through particle-particle collisions. We examine how the local and global
      dissipation of energy by particle-particle and particle-wall collisions depends
      on the number of particles, the velocity of the vibrating base, and the
      restitution coefficients.

PMID- 15244562
TI  - Structural crossover in dense irreversibly aggregating particulate systems.
AB  - Cluster-cluster aggregation has been simulated by off-lattice Monte Carlo methods
      for diffusion-limited (DLCA), ballistic-limited, and reaction-limited cluster
      aggregation classes. We find that as the system evolves and becomes dense, the
      largest cluster develops a hybrid structure with mass fractal dimension D(f)
      approximately 2.6 over large length scales, while at smaller length scales, the
      early time dilute-limit fractal structure is frozen in. The largest cluster is
      thus an aggregate of smaller aggregates with a different fractal dimension, and
      we call it a "superaggregate." The crossover length separating the two
      morphologies, which we call the critical radius of gyration, can be calculated
      based on a simple theory that assumes a monodisperse cluster size distribution.
      This agrees well with simulation results for DLCA. However, for other classes we
      find that the increasing polydispersity in cluster size pushes the simulated
      crossover length radius of gyration to values systematically larger than the
      predicted value.

PMID- 15244563
TI  - Key-lock mechanism in nematic colloidal dispersions.
AB  - We consider the interaction between two-dimensional nematic colloids and planar
      or sculpted walls. The elastic interaction between colloidal disks and flat
      walls, with homeotropic boundary conditions, is always repulsive. These
      repulsions may be turned into strong attractions at structured or sculpted walls,
      with cavities that match closely the shape and size of the colloids. This key
      lock mechanism is analyzed in detail for colloidal disks and spherocylindrical
      cavities of various length to depth ratios, by minimizing the Landau-de Gennes
      free energy functional of the nematic orientational order parameter. We find that
      the attractions occur only for walls with cavities within a small range of the
      colloidal size and a narrow range of orientations with respect to the cavity's
      symmetry axis.

PMID- 15244564
TI  - Anisotropic diffusion-limited aggregation.
AB  - Using stochastic conformal mappings, we study the effects of anisotropic
      perturbations on diffusion-limited aggregation (DLA) in two dimensions. The
      harmonic measure of the growth probability for DLA can be conformally mapped onto
      a constant measure on a unit circle. Here we map m preferred directions for
      growth to a distribution on the unit circle, which is a periodic function with m
      peaks in [-pi,pi) such that the angular width sigma of the peak defines the
      "strength" of anisotropy kappa= sigma(-1) along any of the m chosen directions.
      The two parameters (m,kappa) map out a parameter space of perturbations that
      allows a continuous transition from DLA (for small enough kappa ) to m needlelike
      fingers as kappa--> infinity. We show that at fixed m the effective fractal
      dimension of the clusters D(m,kappa) obtained from mass-radius scaling decreases
      with increasing kappa from D(DLA) approximately 1.71 to a value bounded from
      below by D(min) = 3 / 2. Scaling arguments suggest a specific form for the
      dependence of the fractal dimension D(m,kappa) on kappa for large kappa which
      compares favorably with numerical results.

PMID- 15244565
TI  - Chirality of electrodeposits grown in a magnetic field.
AB  - Electrodeposits grown around a point cathode in a flat, horizontal
      electrochemical cell have fractal form. When grown in the presence of a
      perpendicular applied magnetic field, the deposits develop a spiral structure
      with chirality which reverses on switching the field direction. These structures
      are modeled numerically using biased variants of the diffusion limited
      aggregation (DLA) model. The effects of electric and magnetic fields are modeled
      successfully by varying the probabilities that a random walker will move in a
      given direction as a result of a Coulomb force and the Lorentz force-induced flow
      of electrolyte past the deposit surface. By contrast, a numerical model which
      considers only the effect of the Lorentz force on individual ions, without
      reference to the surface of the growing deposit, produces spiral structures with
      incorrect chirality. The modified DLA model is related to the differential
      equations for diffusion, migration, and convection. Length scales in the problem
      are understood by associating the step length of the random walker with the
      diffusion layer thickness, the lookup radius with the hydrodynamic boundary layer
      thickness and a point on the numerical deposit with a nucleation center for
      growth of a crystallite.

PMID- 15244566
TI  - Synthetic view of two-dimensional aggregation.
AB  - Extensive Monte Carlo simulations using short-range and medium-range interactions
      reveal the existence of quasisteady out-of-equilibrium phases in two-dimensional
      (2D) atom or cluster aggregation at different coverages namely fractal-type,
      dendrites, compact islands with faceted or rough boundaries, as well as gas or
      fluid phases. Different aggregation processes are identified. For medium-range
      effective pair potentials such as the one used for copper atoms, 2D liquid
      droplets are found.

PMID- 15244567
TI  - Diffusion-limited deposition of dipolar particles.
AB  - Deposits of dipolar particles are investigated by means of extensive Monte Carlo
      simulations. We found that the effect of the interactions is described by an
      initial, nonuniversal, scaling regime characterized by orientationally ordered
      deposits. In the dipolar regime, the order and geometry of the clusters depend on
      the strength of the interactions and the magnetic properties are tunable by
      controlling the growth conditions. At later stages, the growth is dominated by
      thermal effects and the diffusion-limited universal regime obtains, at finite
      temperatures. At low temperatures the crossover size increases exponentially as T
      decreases and at T=0 only the dipolar regime is observed.

PMID- 15244568
TI  - Effect of three-body interactions on the phase behavior of charge-stabilized
      colloidal suspensions.
AB  - We study numerically the effect of attractive triplet interactions on the phase
      behavior of suspensions of highly charged colloidal particles at low salinity. In
      our computer simulations, we employ the pair and triplet potentials that were
      obtained from a numerical Poisson-Boltzmann study [Phys. Rev. E 66, 011402
      (2002)]]. On the basis of free energy calculations, we determine the phase
      diagram of an aqueous suspension of identical spheres of diameter sigma=32 nm and
      charge Z=80 as a function of colloid concentration and salinity, both for the
      purely pairwise additive system and for the system with pair and triplet
      interactions. The main effect of including the triplet interactions is a
      destabilization of the body-centered-cubic (bcc) crystal phase in favor of the
      face-centered-cubic (fcc) crystal phase. As a consequence the phase diagram
      features the coexistence of a rather dilute fluid with an almost-close-packed fcc
      phase at low salinity and bcc-fcc coexistence with a big density jump at
      intermediate salinity. The triplet attractions do not affect the phase behavior
      at sufficiently high salinity; under these conditions the system is well
      described by the pairwise potential.

PMID- 15244569
TI  - Dynamics of normal and superfluid fogs using diffusing-wave spectroscopy.
AB  - The dynamics of normal and superfluid fogs are studied using the technique of
      diffusing-wave spectroscopy. For a water fog generated with a 1.75 MHz
      piezoelectric driver below the liquid surface, the 7 microm diameter droplets are
      found to have diffusive dynamics for correlation times long compared to the
      viscous time. For a fog of 10 microm diameter superfluid helium droplets in
      helium vapor at 1.5 K the motion appears to be ballistic for correlation times
      short compared to the viscous time. The velocity correlations between the helium
      droplets are found to depend on the initial velocity with which the droplets are
      injected from the helium surface into the fog.

PMID- 15244570
TI  - Coarsening dynamics of ternary amphiphilic fluids and the self-assembly of the
      gyroid and sponge mesophases: Lattice-Boltzmann simulations.
AB  - By means of a three-dimensional amphiphilic lattice-Boltzmann model with short
      range interactions for the description of ternary amphiphilic fluids, we study
      how the phase separation kinetics of a symmetric binary immiscible fluid is
      altered by the presence of the amphiphilic species. We find that a gradual
      increase in amphiphile concentration slows down domain growth, initially from
      algebraic to logarithmic temporal dependence, and, at higher concentrations, from
      logarithmic to stretched-exponential form. In growth-arrested stretched
      exponential regimes, at late times we observe the self-assembly of sponge
      mesophases and gyroid liquid-crystalline cubic mesophases, hence confirming that
      (a) amphiphile-amphiphile interactions need not be long-ranged in order for
      periodically modulated structures to arise in a dynamics of competing
      interactions, and (b) a chemically specific model of the amphiphile is not
      required for the self-assembly of cubic mesophases, contradicting claims in the
      literature. We also observe a structural order-disorder transition between sponge
      and gyroid phases driven by amphiphile concentration alone or, independently, by
      the amphiphile-amphiphile and the amphiphile-binary fluid coupling parameters.
      For the growth-arrested mesophases, we also observe temporal oscillations in the
      structure function at all length scales; most of the wave numbers show slow
      decay, and long-term stationarity or growth for the others. We ascribe this
      behavior to a combination of complex amphiphile dynamics leading to Marangoni
      flows.

PMID- 15244571
TI  - Two-dimensional lattice-fluid model with waterlike anomalies.
AB  - We investigate a lattice-fluid model defined on a two-dimensional triangular
      lattice, with the aim of reproducing qualitatively some anomalous properties of
      water. Model molecules are of the "Mercedes Benz" type, i.e., they possess a D3
      (equilateral triangle) symmetry, with three bonding arms. Bond formation depends
      both on orientation and local density. We work out phase diagrams, response
      functions, and stability limits for the liquid phase, making use of a generalized
      first order approximation on a triangle cluster, whose accuracy is verified, in
      some cases, by Monte Carlo simulations. The phase diagram displays one ordered
      (solid) phase which is less dense than the liquid one. At fixed pressure the
      liquid phase response functions show the typical anomalous behavior observed in
      liquid water, while, in the supercooled region, a reentrant spinodal is observed.

PMID- 15244572
TI  - Ubiquity of domain patterns in sheared viscoelastic fluids.
AB  - A ubiquitous domain pattern is observed in two-phase viscoelastic fluids falling
      within the simple paradigm of soft viscoelastic domains suspended in a less
      viscoelastic fluid under shear flow. Three strikingly different complex fluids
      exhibit the same shear-induced domain structure, which we relate to the
      elasticity of the dispersed phase via an approximate Weissenberg number. We
      suggest a physical mechanism for the formation of this pervasive pattern,
      independent of the dynamic origin of the elasticity of the suspended phase.

PMID- 15244573
TI  - Dynamics of growth in a three-component mixture with competing interactions.
AB  - We study numerically the dynamics, in two dimensions, of phase separation in
      ternary mixtures with dipolar interactions which lead to the formation of
      modulated phases. We distinguish three different modulated phases: a hexagonal
      phase of droplets, a lamellar phase, and a hexagonal phase of bubbles. Inside the
      crystal structures an additional phase separation occurs "coloring" the texture.
      The dynamics in the droplet phase mixes the two kinds of droplets of different
      composition. The lamellar phase does not evolve toward parallel lamellae, and the
      phase separation inside the channels proceeds until they reach a grain boundary.
      The hexagonal bubble phase is never formed due to the phase separation that forms
      an interface of bubbles which blocks the contact between the two phases. In its
      place we find an unsuspected lamellar phase.

PMID- 15244574
TI  - Fragility in p-spin models.
AB  - We investigate the relation between fragility and phase space properties - such
      as the distribution of states - in the mean-field p -spin model, a solvable model
      that has been frequently used in studies of the glass transition. By direct
      computation of all the relevant quantities, we find that (i) the recently
      observed correlation between fragility and vibrational properties at low
      temperature is present in this model and (ii) the total number of states is a
      decreasing function of fragility, at variance with what is currently believed. We
      explain these findings by taking into account the contribution to fragility
      coming from the transition paths between different states. Finally, we propose a
      geometric picture of the phase space that explains the correlation between
      properties of the transition paths, distribution of states, and their vibrational
      properties. However, our analysis may not apply to strong systems where
      inflection points in the configurational entropy as a function of the temperature
      are found.

PMID- 15244575
TI  - Ising fluids in an external magnetic field: an integral equation approach.
AB  - The phase behavior of Ising spin fluids is studied in the presence of an external
      magnetic field with the integral equation method. The calculations are performed
      on the basis of a soft mean spherical approximation using an efficient algorithm
      for solving the coupled set of the Ornstein-Zernike equations, the closure
      relations, and the external field constraint. The phase diagrams are obtained in
      the whole thermodynamic space including the magnetic field H for a wide class of
      Ising fluid models with various ratios R of the strengths of magnetic to
      nonmagnetic Yukawa-like interactions. The influence of varying the inverse
      screening lengths z(1) and z(2), corresponding to the magnetic and nonmagnetic
      Yukawa parts of the potential, is investigated too. It is shown that changes in R
      as well as in z(1) and z(2) can lead to different topologies of the phase
      diagrams. In particular, depending on the value of R, the critical temperature of
      the liquid-gas transition either decreases monotonically, behaves
      nonmonotonically, or increases monotonically with increasing H. The para-ferro
      magnetic transition is also affected by changes in R and the screening lengths.
      At H=0, the Ising fluid maps onto a simple model of a symmetric nonmagnetic
      binary mixture. For H--> infinity, it reduces to a pure nonmagnetic fluid. The
      results are compared with available simulations and the predictions of other
      theoretical methods. It is demonstrated that the mean spherical approximation
      appears to be more accurate compared with mean field theory, especially for
      systems with short ranged attraction potentials (when z(1) and z(2) are large).
      In the Kac limit z(1), z(2) -->+0, both approaches tend to nearly the same
      results.

PMID- 15244576
TI  - Modeling and simulation for phase coarsening: a comparison with experiment.
AB  - The phase coarsening of precipitates is modeled in the framework of Debye-Huckel
      theory. The interactions observed among a population of precipitates dispersed
      throughout a matrix can be described by diffusion screening. The relationship
      between the maximum particle radius and the volume fraction of the phases is
      established, and the rate of coarsening is related to the volume fraction and the
      self-similar particle size distribution. We simulated the dynamics of late-stage
      phase separation using multiparticle diffusion methods. Experimental measurements
      on the rates of coarsening of delta(') ( Al3 Li) precipitates in binary Al-Li
      alloys are compared with our results using modeling and simulation. The
      theoretically predicted particle size distributions and the maximum radius
      expected for particles in the microstructure agree well with recent experimental
      results.

PMID- 15244577
TI  - Can a droplet break up under flow without elongating? Fragmentation of smectic
      monodisperse droplets.
AB  - We study the fragmentation under shear flow of smectic monodisperse droplets at
      high volume fraction. Using small angle light scattering and optical microscopy,
      we reveal the existence of a break-up mechanism for which the droplets burst into
      daughter droplets of the same size. Surprisingly, this fragmentation process,
      which is strain controlled and occurs homogeneously in the cell, does not require
      any transient elongation of the droplets. Systematic experiments as a function of
      the initial droplet size and the applied shear rate show that the rupture is
      triggered by an instability of the inner droplet structure.

PMID- 15244578
TI  - Role of the density in the crossover region of o-terphenyl and poly(vinyl
      acetate).
AB  - The coupling between the reorientation of molecular probes and the density in one
      low-molar mass glass former [ o -terphenyl (OTP)] and one polymer [poly(vinyl
      acetate) (PVAc)] is studied in the Goldstein's crossover region where the
      structural (alpha) and the secondary (beta) relaxations bifurcate. The coupling
      is found to be strong in OTP and virtually absent in PVAc. The probes sense both
      the alpha and beta relaxations, and locate their splitting accurately. It is
      concluded that the density affects the relaxation occurring in the crossover
      region of OTP but not of PVAc at subnanometer length scales. The findings are
      compared with recent assessments of the role of the molecular packing close and
      above the glass transition temperature T(g).

PMID- 15244579
TI  - Compression of a capsule: mechanical laws of membranes with negligible bending
      stiffness.
AB  - The compression of a capsule between two plates is considered. The problem is
      solved numerically for a capsule made of an incompressible liquid drop surrounded
      by a thin elastic membrane which has a negligible bending stiffness. Numerical
      results are provided for three different mechanical laws of the membrane. By
      considering elastic moduli independent of the deformation, we show that the
      isotropic dilation plays the major role. In particular, an asymptotic behavior
      independent of the shear modulus is found for large deformations. For more
      complex models, the deformation limits beyond which the variation of elastic
      moduli starts to play a role are examined. The results indicate that the
      distinction between the different models requires a careful inspection of both
      small and large deformations. The theoretical predictions are compared with
      experimental results. For millimetric capsules with membranes made of covalently
      linked human serum albumin and alginate, the best agreement is obtained by
      considering that the elastic moduli are independent of the deformation and range
      from 0.1 to 4 N/m.

PMID- 15244580
TI  - Model for spreading of liquid monolayers.
AB  - Manipulating fluids at the nanoscale within networks of channels or chemical
      lanes is a crucial challenge in developing small scale devices to be used in
      microreactors or chemical sensors. In this context, ultrathin (i.e., monolayer)
      films, experimentally observed in spreading of nanodroplets or upon extraction
      from reservoirs in capillary rise geometries, represent an extreme limit which is
      of physical and technological relevance since the dynamics is governed solely by
      capillary forces. In this work we use kinetic Monte Carlo (KMC) simulations to
      analyze in detail a simple, but realistic model proposed by Phys. Rev. Lett. 76,
      86 (1996)]] for the two-dimensional spreading on homogeneous substrates of a
      fluid monolayer which is extracted from a reservoir. Our simulations confirm the
      previously predicted time dependence of the spreading, X ( t--> infinity ) =A
      square root of t, with X (t) as the average position of the advancing edge at
      time t, and they reveal a nontrivial dependence of the prefactor A on the
      strength U0 of interparticle attraction and on the fluid density C0 at the
      reservoir as well as an U0 -dependent spatial structure of the density profile of
      the monolayer. The asymptotic density profile at long time and large spatial
      scale is carefully analyzed within the continuum limit. We show that including
      the effect of correlations in an effective manner into the standard mean-field
      description leads to predictions both for the value of the threshold interaction
      above which phase segregation occurs and for the density profiles in excellent
      agreement with KMC simulation results.

PMID- 15244581
TI  - Field theoretic calculation of the surface tension for a model electrolyte
      system.
AB  - We carry out the calculation of the surface tension for a model electrolyte to
      first order in a cumulant expansion about a free-field theory equivalent to the
      Debye-Huckel approximation. In contrast with previous calculations, the surface
      tension is calculated directly without recourse to integrating thermodynamic
      relations. The system considered is a monovalent electrolyte with a region at the
      interface, of width h, from which the ionic species are excluded. In the case
      where the external dielectric constant epsilon(0) is smaller than the electrolyte
      solution's dielectric constant epsilon we show that the calculation at this order
      can be fully regularized. In the case where h is taken to be zero the Onsager
      Samaras limiting law for the excess surface tension of dilute electrolyte
      solutions is recovered, with corrections coming from a nonzero value of
      epsilon(0) /epsilon.

PMID- 15244582
TI  - Interfacial structure at a two-dimensional wedge filling transition: Exact
      results and a renormalization group study.
AB  - Interfacial structure and correlation functions near a two-dimensional wedge
      filling transition are studied using effective interfacial Hamiltonian models. An
      exact solution for short range binding potentials and results for Kratzer binding
      potentials show that sufficiently close to the filling transition a new length
      scale emerges and controls the decay of the interfacial profile relative to the
      substrate and the correlations between interfacial positions above different
      positions. This new length scale is much larger than the intrinsic interfacial
      correlation length, and it is related geometrically to the average value of the
      interfacial position above the wedge midpoint. The interfacial behavior is
      consistent with a breather mode fluctuation picture, which is shown to emerge
      from an exact decimation functional renormalization group scheme that keeps the
      geometry invariant.

PMID- 15244583
TI  - Phase behavior of a binary symmetric mixture in slitlike pores with opposing
      walls: application of density functional approach.
AB  - We study adsorption of a symmetric binary Lennard-Jones mixture, which exhibits
      partial mixing in a bulk phase, in slitlike pores formed by the walls having
      antisymmetric properties with respect to the components. The calculations are
      carried out by means of a density functional approach. We show that under
      suitable conditions the pore filling may occur as a sequence of two first-order
      transitions. The capillary condensation may lead to an "antisymmetric" liquidlike
      film, the symmetry of which follows the symmetry of the adsorbing potential, or
      to a "demixed" film, the symmetry of which is only weakly associated with the
      symmetry of the adsorption potential. The additional first-order antisymmetric
      demixed film transition begins at the triple point temperature and ends at the
      critical end point temperature.

PMID- 15244584
TI  - Numerical simulation of a continuum model of growth of thin composite films.
AB  - We present the results of extensive numerical integration in ( 1+1 ) dimensions
      of a set of equations that couple the Kardar-Parisi-Zhang (KPZ) equation to the
      time-dependent Ginzburg-Landau (TDGL) equation, recently proposed for modeling
      the growth of thin composite solid films. We find that for times t shorter than a
      crossover time t(c) the mean domain size L(t) grows logarithmically with the
      time, whereas for t>> t(c) L(t) grows as t(1/ z(m) ), with z(m) being
      nonuniversal and depending on the parameters of the model. The roughness exponent
      is also found to be nonuniversal. Thus, neither the dynamics of the domains'
      growth is governed by the TDGL equation, nor is the scaling of the surface
      roughness described by the KPZ equation.

PMID- 15244585
TI  - Relaxation processes in Langmuir films under lateral compression.
AB  - The orientational relaxation process of the director n to its equilibrium
      orientation n(eq), in the Langmuir film, during the lateral compression in
      absence of flow, is investigated. The relaxation time, during compression of 4-n
      pentyl- 4(') -cyanobiphenyl monolayer (multilayer) films on the water surface,
      using the Ericksen-Leslie theory, has been calculated for a number of dynamic
      regimes. It is also shown that the viscous and electric forces exerted per unit
      volume of the monolayer Langmuir film may excite the solitary wave propagating
      along the air-water interface.

PMID- 15244586
TI  - Persistence in nonequilibrium surface growth.
AB  - Persistence probabilities of the interface height in ( 1+1 ) - and ( 2+1 ) 
      dimensional atomistic, solid-on-solid, stochastic models of surface growth are
      studied using kinetic Monte Carlo simulations, with emphasis on models that
      belong to the molecular beam epitaxy (MBE) universality class. Both the initial
      transient and the long-time steady-state regimes are investigated. We show that
      for growth models in the MBE universality class, the nonlinearity of the
      underlying dynamical equation is clearly reflected in the difference between the
      measured values of the positive and negative persistence exponents in both
      transient and steady-state regimes. For the MBE universality class, the positive
      and negative persistence exponents in the steady-state are found to be
      theta(S)(+) =0.66+/-0.02 and theta(S)(-) =0.78+/-0.02, respectively, in ( 1+1 )
      dimensions, and theta(S)(+) =0.76+/-0.02 and theta(S)(-) =0.85+/-0.02,
      respectively, in ( 2+1 ) dimensions. The noise reduction technique is applied on
      some of the ( 1+1 ) -dimensional models in order to obtain accurate values of the
      persistence exponents. We show analytically that a relation between the steady
      state persistence exponent and the dynamic growth exponent, found earlier to be
      valid for linear models, should be satisfied by the smaller of the two steady
      state persistence exponents in the nonlinear models. Our numerical results for
      the persistence exponents are consistent with this prediction. We also find that
      the steady-state persistence exponents can be obtained from simulations over
      times that are much shorter than that required for the interface to reach the
      steady state. The dependence of the persistence probability on the system size
      and the sampling time is shown to be described by a simple scaling form.

PMID- 15244587
TI  - Self-assembled nanoparticle deposits formed at the contact line of evaporating
      micrometer-size droplets.
AB  - We report on the formation of self-assembled rings of Co Pt3 nanoparticles (ring
      diameter ranging from 0.6 to 1.5 microm, particle diameter 6 nm ) formed in an
      evaporating thin film. The latter was achieved on the surface of water by
      spreading a binary mixture composed of two solutions: nitrocellulose dissolved in
      amyl acetate and Co Pt3 particles stabilized by hexadecylamine dissolved in
      hexane. The self-assembly process of the nanometer-sized particles into
      micrometer-sized rings results from phase separation in a thin film of the mixed
      solutions, leading to a bilayer, and the subsequent decomposition during solvent
      evaporation of the top hexadecylamine-rich layer into droplets. Finally, the
      evaporation of the remaining solvent from these droplets gives rise to a
      retraction of their contact line. The Co Pt3 particles located at the contact
      line follow its motion and self-assemble along this line.

PMID- 15244588
TI  - Modified cellular automaton model for the prediction of dendritic growth with
      melt convection.
AB  - A modified cellular automaton (MCA) coupled with a momentum and species transport
      model has been developed in order to predict the evolution of dendritic
      morphology during solidification of alloys in the presence of melt convection. In
      the present model, the cellular automaton algorithm for dendritic growth is
      incorporated with the transport model, for calculating fluid flow and mass
      transfer by both convention and diffusion. The MCA model takes into account the
      effects of the constitutional undercooling and the curvature undercooling on the
      equilibrium interface temperature. It also considers the preferred growth
      orientation of crystals and solute redistribution during solidification. In the
      transport model, which is coupled with cellular automaton approach, the SIMPLE
      scheme is employed to solve the governing equations of momentum and species
      transfers. The present model was applied to model solutal dendritic growth of an
      Al-3mass%Cu alloy in a forced flow. The simulations reproduced the typical
      asymmetric growth features of convective dendrites with various preferred
      orientations. The effects of inlet flow velocity on the solute redistribution and
      the growth velocity of a dendritic tip were quantitatively investigated.

PMID- 15244589
TI  - Boundary lubrication with a glassy interface.
AB  - Recently introduced constitutive equations for the rheology of dense, disordered
      materials are investigated in the context of stick-slip experiments in boundary
      lubrication. The model is based on a generalization of the shear transformation
      zone (STZ) theory, in which plastic deformation is represented by a population of
      mesoscopic regions which may undergo nonaffine deformations in response to
      stress. The generalization we study phenomenologically incorporates the effects
      of aging and glassy relaxation. Under experimental conditions associated with
      typical transitions from stick-slip to steady sliding and stop-start tests, these
      effects can be dominant, although the full STZ description is necessary to
      account for more complex, chaotic transitions.

PMID- 15244590
TI  - Onset and manipulation of self-assembled morphology in freely standing polymer
      trilayer films.
AB  - We have used reflected light microscopy to study the lateral morphology which
      self-assembles at elevated temperatures in films consisting of a polyisoprene
      (PI) layer capped on both sides by polystyrene (PS) layers: freely standing
      PS/PI/PS trilayer films. Heating of the trilayer films causes the formation of a
      periodic, lateral morphology which is driven by the attractive dispersion
      interaction acting across the film. In our studies of the temperature dependence
      of the morphology, we find that the onset temperature for the formation of the
      morphology increases with increasing heating rate. By heating the films to
      temperatures greater than the glass transition temperature of the PS-capping
      layers, the morphology is removed. By heating and then cooling the films, the
      morphology formed upon heating disappears and reforms at right angles to the
      original morphology with a larger periodicity characteristic of the lower
      temperature. These results can be explained by considering the time and
      temperature dependence of Young's modulus of PS.

PMID- 15244591
TI  - Statistical mechanics of fluids adsorbed in planar wedges: finite contact angle.
AB  - I consider the statistical mechanics of inhomogeneous fluids applied to fluids
      adsorbed in planar wedges. Exact results are described that belong to an infinite
      subset of models defined as the intersection of any two identical semi-infinite
      planar wall-fluid potentials. This geometry is interesting as a generic example
      of adsorption onto structured interfaces and of interfacial phase transitions
      controlled by the substrate geometry. Previously described virial theorems are
      extended to the case of a general wall-fluid model. This enables the
      consideration of wedge filling when Young's contact angle far from the wedge apex
      is finite. The virial theorems generate two important relations: the wedge sum
      rules. The first sum rule links the interfacial free energy far from the wedge
      apex to the structure induced at the apex. The second sum rule links the free
      energy of the apex region to the structure induced by the apex. When Young's
      contact angle at the wedge walls is finite these relations further yield an exact
      result for the macroscopic contact angle in terms of the nanoscopic structure at
      the three-phase contact line (the intersection of the liquid-vapor surface with a
      wedge wall): the contact angle sum rule. These exact results are of direct
      relevance to computer simulation studies of adsorbed films. In addition, they
      take on special significance in the vicinity of continuous interfacial phase
      transitions: an approach to complete filling and the filling transition at bulk
      liquid-vapor coexistence.

PMID- 15244592
TI  - Coexistence of polar and nonpolar domains and their photocontrol in the B7 phase
      of a bent-core liquid crystal containing azo dyes.
AB  - Coexisting polar and nonpolar domains have been studied by means of texture
      observation, x-ray analysis, optical second-harmonic generation (SHG), and SHG
      microscopy in the B7 phase of a bent-core mesogen doped with azo dyes. The bent
      core molecules take a planar orientation and show high birefringence in the polar
      domain, while they take a homeotropic orientation and show low birefringence in
      the nonpolar domain. Good correspondence between real and SHG images was observed
      under a SHG microscope; the bright (high-birefringent) domain is SHG active and
      the dark (low-birefringent) domain is not SHG active. Photoisomerization of the
      azo dyes causes layer reorientation from the layer perpendicular to the substrate
      to that parallel to it.

PMID- 15244593
TI  - Evidence for different polymorphisms with and without an external electric field
      in a series of bent-shaped molecules.
AB  - Five fluid tilted mesophases are observed in a series of achiral banana-shaped
      compounds. The terminal chain length is the pertinent molecular parameter which
      induces the polymorphism change. All the phases, refer to tilted lamellar
      structure without in-plane order in the layers. The observation of monolayer,
      bilayer, ribbon phase, and undulated structures recalls the richness of the
      polymorphism of the frustrated polar calamitic liquid crystals. Among the
      mesophases, we highlight two: a Sm-C G2 phase corresponding to a bilayer
      structure made of Sm-CG layers, and its two-dimensional variant, Sm- Ctilde; G2.
      The five mesophases observed at zero field are switchable under electric field.
      At least three ferroelectric phases are induced by an applied field. There is no
      direct correspondence between the zero field phases and the phases observed under
      electric field. These observations show that different polymorphisms exist in the
      series with and without an applied field. A unique ( E,T ) phase diagram is
      presented, corresponding to the superposition of the ( E,T ) diagrams obtained
      for each homolog of the series, where the influence of the chain length is
      equivalent to a shift on the temperature axis.

PMID- 15244594
TI  - Potential of mean force between a spherical particle suspended in a nematic
      liquid crystal and a substrate: sphere size effects.
AB  - The expanded ensemble density of states method (ExEDOS) is used to investigate
      the effective interaction of a spherical colloidal particle suspended in a
      confined liquid crystal (LC) with a substrate. The potential of mean force (PMF)
      is determined as a function of the normal distance between the particle and the
      substrate's surface. The presence of the substrate induces a layered structure of
      the LC, which in turn greatly influences the PMF. We analyze the structure of the
      Saturn ring defect that accompanies the colloidal sphere, and find that the ring
      is displaced slightly towards the surface when the sphere is within the first LC
      surface layer. A transition occurs from an overall attraction of the colloid to
      the substrate to a global repulsion when the sphere's radius is roughly twice the
      length of the LC molecules.

PMID- 15244595
TI  - Landau-de Gennes model for nonuniform configurations in nematic liquid
      crystalline elastomers.
AB  - Through a mean field theory, an elastic free energy describing the nonuniform
      elastic textures observed in nematic elastomers, is proposed. To construct it, an
      order parameter that describes the nematic-isotropic phase transition through the
      change of the elastic properties of the strain tensor at the transition point is
      introduced. The resulting elastic free energy can be written in a form that
      resembles the Frank free energy of the usual nematic liquid crystals, becoming
      equivalent to it when the size of the elastic nematic domains is a fixed constant
      along the whole sample. Using this approach, a model for nonhomogeneous
      deformations found by Macromolecules 33, 7675 (2000)] in elastomeric thin films
      of urethane/urea is proposed.

PMID- 15244596
TI  - Computer simulation of a liquid-crystal anchoring transition.
AB  - We present a study of the effects of confinement on a system of hard Gaussian
      overlap particles interacting with planar substrates through the hard-needle-wall
      potential. Using geometrical arguments to calculate the molecular volume absorbed
      at the substrates, we show that both planar and homeotropic arrangements can be
      obtained using this model. Monte Carlo simulations are then used to perform a
      systematic study of the model's behavior as a function of the system density and
      the hard-needle-wall interaction parameter. As well as showing the homeotropic to
      planar anchoring transition, the anchoring phase diagrams computed from these
      simulations indicate regions of bistability. This bistable behavior is examined
      further through the explicit simulation of field-induced two-way switching
      between the two arrangements.

PMID- 15244597
TI  - First-order isotropic-smectic-A transition in liquid-crystal-aerosil gels.
AB  - The short-range order which remains when the isotropic to smectic- A transition
      is perturbed by a gel of silica nanoparticles (aerosils) has been studied using
      high-resolution synchrotron x-ray diffraction. The gels have been created in situ
      in decylcyanobiphenyl, which has a strongly first-order isotropic to smectic- A
      transition. The effects are determined by detailed analysis of the temperature
      and gel density dependence of the smectic structure factor. In previous studies
      of the continuous nematic to smectic- A transition in a variety of thermotropic
      liquid crystals the aerosil gel appeared to pin, at random, the phase of the
      smectic density modulation. For the isotropic to smectic- A transition the same
      gel perturbation yields different results. The smectic correlation length
      decreases more slowly with increasing random-field variance in good quantitative
      agreement with the effect of a random pinning field at a transition from a
      uniform phase directly to a phase with one-dimensional translational order. We
      thus compare the influence of random fields on a freezing transition with and
      without an intervening orientationally ordered phase.

PMID- 15244598
TI  - Surface-induced orientational phase transition in a lyotropic liquid crystal
      observed by nonlinear optical techniques.
AB  - We have observed a phase transition from a uniaxial to a biaxial nematic phase in
      a lyotropic liquid crystal as a function of decreasing film thickness. The
      results, obtained by optical second-harmonic generation experiments in a wedged
      cell geometry, are supported by additional Z -scan measurements and can be
      interpreted by wall-induced ordering effects.

PMID- 15244599
TI  - Photorefractive effect due to a photoinduced surface-charge modulation in undoped
      liquid crystals.
AB  - We demonstrate that some peculiarities of the surface-induced photorefractive
      effect (SIPRE) in undoped nematic planar cells can be simply explained
      considering the electric field induced by a modulated surface-charge
      distribution. Polarization-dependent forced light scattering and two-beam
      coupling experiments indicate that the observed anisotropy of the diffraction
      efficiency and the energy transfer between the pump beams strongly depend on the
      experimental geometry. The investigation suggests that the unusual dichotomy
      between local and nonlocal behavior can be ascribed to a modulated longitudinal
      electric field component, in phase with the interference pattern, which is not
      accountable by the conventional photorefractivity. In a simple and general
      approach we demonstrate that the conceived charge distribution model for the
      SIPRE produces a space-charge field having two orthogonal modulated components,
      in-phase and pi/2 out of phase, respectively. The electric field configuration
      within the nematic sample gives reason for the main experimental features.

PMID- 15244600
TI  - Molecular reorientations in liquid crystals pentyloxybenzylidine hexylanilene
      (PBHA) and butyloxybenzylidine octylanilene (BBOA).
AB  - Molecular reorientational motions in undeuterated pentyloxybenzylidine
      hexylanilene (PBHA or 5O.6) and butyloxybenzylidine octylanilene (BBOA or 4O.8)
      as studied by the quasielastic neutron scattering (QENS) technique in their
      different mesophases are reported. Models are built up in stages to account for
      the experimental elastic incoherent structure factor (EISF). It is found that
      there exist simultaneous reorientational motions of the chain group and the
      reorientational motions of the whole molecule around its molecular axis in the
      smectic- G, smectic- B, and smectic- C phases. In smectic- A and nematic phases,
      additional body axis fluctuations are found to exist in both 5O.6 and 4O.8
      systems. The average amplitude of body axis fluctuations is found to be
      approximately 15 degrees and 25 degrees, respectively, in the smectic- A and
      nematic phases of 5O.6, and approximately 14 degrees and 29 degrees,
      respectively, in 4O.8.

PMID- 15244601
TI  - Theory of chiral periodic mesophases formed from an achiral liquid of bent-core
      molecules.
AB  - The theory of unconventional one-dimensional periodic mesophases forming in a
      liquid of achiral bent-core molecules is presented. The order parameter is a
      polarization wave. Three distinct phases which can be stabilized directly from
      the isotropic liquid phase are associated with linear, circular, and elliptic
      polarizations of the wave. The elliptic polarization leads to the structure of
      the commonly studied B2 "bent-core" mesophase whereas the recently discovered
      C(p) phase may be assigned to the linear polarization. We present the molecular
      configurations and macroscopic properties of the stable states. Their behavior
      under chiral doping and electric field application are investigated and the
      corresponding phase diagrams are calculated.

PMID- 15244602
TI  - Relationship between surface order and surface azimuthal anchoring strength of
      nematic liquid crystals.
AB  - The liquid-crystal molecular order near the rubbed polymer surface is reexamined
      by the improved torque balance method. The surface azimuthal anchoring strength
      measured by the improved torque balance method is several times larger than that
      believed conventionally, considered to be significantly affected by the phase
      transition behavior. Based on this result, it can be argued that the correlation
      between the rubbing strength and the surface azimuthal anchoring strength should
      be improved in consideration of the mechanism of surface order.

PMID- 15244603
TI  - Bulk inhomogeneous phases of anisotropic particles: a fundamental measure
      functional study of the restricted orientations model.
AB  - The phase diagram of prolate and oblate particles in the restricted orientations
      approximation (Zwanzig model) is calculated. Transitions to different
      inhomogeneous phases (smectic, columnar, oriented, or plastic solid) are studied
      through minimization of the fundamental measure functional (FMF) of hard
      parallelepipeds. The study of parallel hard cubes (PHC's) as a particular case is
      also included motivated by recent simulations of this system. As a result a rich
      phase behavior is obtained which include, apart from the usual liquid crystal
      phases, a very peculiar phase (called here discotic smectic) which was already
      found in the only existing simulation of the model, and which turns out to be
      stable because of the restrictions imposed on the orientations. The phase diagram
      is compared at a qualitative level with simulation results of other anisotropic
      particle systems.

PMID- 15244604
TI  - Diffusion model of photoaligning in azo-dye layers.
AB  - The model of the rotational diffusion of the azo-dye molecules under the action
      of polarized uv light was used to explain the formation of the photoinduced order
      in azo-dye layers. We consider both the approximations of negligible and strong
      molecular interaction during the process of the reorientation under the field of
      a polarized light. We constructed an experimental setup, based on a photoelastic
      modulator, that allows accurate in situ measurements of the phase retardation
      delta of thin film as a function of the exposure time t(exp) and exposure power W
      (W/ cm(2) ). A good agreement with experiment was observed. Fitting the
      experimental curves delta ( t(exp) ) for different power values W, we can
      estimate the coefficient of rotational diffusion D, azo-dye order parameter S (
      t(exp) ), and other parameters of the rotational diffusion model.

PMID- 15244605
TI  - Traveling waves in ferroelectric smectic-C liquid crystals.
AB  - This article investigates, by means of Lie point symmetries, traveling wave
      solutions to a dynamic equation that frequently arises in the theory of
      ferroelectric smectic- C liquid crystals under the influence of an electric
      field. The equation considered has three sinusoidal nonlinearities and possible
      time-dependent solutions are discussed in the context of minima and maxima of the
      electric energy density for these liquid crystals: solutions travel between such
      constant equilibrium states. Implicit solutions to an approximation of the
      governing dynamic equation are determined. Nondimensional control parameters that
      characterize changes in the availability of equilibrium states as the magnitude
      of the field increases are also identified.

PMID- 15244606
TI  - Tunable photonic defect modes in a cholesteric liquid crystal induced by optical
      deformation of helix.
AB  - We have demonstrated, based on numerical analyses, that the introduction and
      tuning of photonic defect modes in a cholesteric liquid crystal (CLC) can be
      realized by the local deformation of its one-dimensional periodic helical
      structure. The defect modes appear in transmission spectra only when incident
      circularly polarized light has the same handedness as CLC's. The tuning of defect
      modes position can be performed upon both local elongation and shortening of the
      helix; however, the direction of the shift of the defect mode wavelength is
      opposite. By controlling the degree of the deformation of helix, a continuous
      shift of the defect modes can be realized. Our results will open the way for the
      optical introduction and tuning of defect modes in CLC's.

PMID- 15244607
TI  - Field control of the surface electroclinic effect in chiral smectic-A liquid
      crystals.
AB  - The surface electroclinic effect, which causes an azimuthal deviation of the
      layer normal from the surface rubbing direction in cells of chiral smectic- A
      liquid crystals, can be eliminated (and even reversed) by applying an electric
      field during cooling from the isotropic phase. The observed dependence of layer
      orientation on field strength leads to a model in which the surface electroclinic
      tilt results from an effective surface electric field. The experiements suggest a
      general method for controlling the azimuthal layer alignment of chiral smectic
      cells.

PMID- 15244608
TI  - Static properties of a simulated supercooled polymer melt: structure factors,
      monomer distributions relative to the center of mass, and triple correlation
      functions.
AB  - We analyze structural and conformational properties in a simulated bead-spring
      model of a nonentangled, supercooled polymer melt. We explore the statics of the
      model via various structure factors, involving not only the monomers, but also
      the center of mass (CM). We find that the conformation of the chains and the CM
      CM structure factor, which is well described by a recently proposed approximation
      [Europhys. Lett. 58, 53 (2002)]], remain essentially unchanged on cooling toward
      the critical glass transition temperature T(c) of mode-coupling theory. Spatial
      correlations between monomers on different chains, however, depend on
      temperature, albeit smoothly. This implies that the glassy behavior of our model
      cannot result from static intrachain or CM-CM correlations. It must be related to
      interchain correlations at the monomer level. Additionally, we study the
      dependence of interchain correlation functions on the position of the monomer
      along the chain backbone. We find that this site dependence can be well accounted
      for by a theory based on the polymer reference interaction site model. We also
      analyze triple correlations by means of the three-monomer structure factors for
      the melt and for the chains. These structure factors are compared with the
      convolution approximation that factorizes them into a product of two-monomer
      structure factors. For the chains this factorization works very well, indicating
      that chain connectivity does not introduce special triple correlations in our
      model. For the melt deviations are more pronounced, particularly at wave vectors
      close to the maximum of the static structure factor.

PMID- 15244609
TI  - Role of curvature elasticity in sectorization and ripple formation during melt
      crystallization of polymer single crystals.
AB  - The present article focuses on theoretical elucidation of possible effect of
      mechanical deformation on spatio-temporal emergence of unusual polymer morphology
      subjected to quiescent isothermal crystallization conditions. The present theory
      developed is based on a phase field model consisted of non-conserved time
      dependent Ginzburg-Landau equation having an asymmetric double well potential in
      the crystal order parameter signifying metastability for crystallization, coupled
      with the chain tilt angle involving curvature elasticity and strain recovery
      potentials. Under quiescent crystallization conditions, the curvature elasticity
      term is needed to discern the emergence of sectorized single crystals. Upon
      coupling with the strain recovery potential, the numerical calculation captures
      ripple formation running across the long lamellar growth front, which may be
      attributed to lamellar buckling caused by the volume shrinkage. Of particular
      interest is that these simulated topologies of the single crystals are in good
      accord with the growth character of syndiotactic polypropylene single crystals
      observed experimentally by us during isothermal crystallization from the melt.

PMID- 15244610
TI  - Thermal expansion behavior of ultrathin polymer films supported on silicon
      substrate.
AB  - The thermal expansion behavior of polystyrene (PS) thin films was investigated
      using x-ray reflectivity, focusing on ultrathin films below 10 nm. It was found
      that the glass transition temperature T(g) decreases with thickness as reported
      by many researchers while it is almost independent of thickness and constant at
      354 K for films below approximately 10 nm. The thickness dependence of T(g) was
      well reproduced by a two-layer model consisting of a mobile surface layer with
      T(g) of 354.5 K and a bulklike layer with T(g) of 373 K ( =bulk T(g) ),
      suggesting that the so-called immobile dead layer near the substrate is
      negligible or very thin in this system. This surface T(g) of 354 K was confirmed
      by the relaxation of surface roughness of as-deposited films at about 354 K. It
      was also found that the thermal expansivity decreases with thickness in the
      glassy state as well as in the molten state while the reduction is smaller in the
      molten state.

PMID- 15244611
TI  - Extinction dynamics of Lotka-Volterra ecosystems on evolving networks.
AB  - We study a model of a multispecies ecosystem described by Lotka-Volterra-like
      equations. Interactions among species form a network whose evolution is
      determined by the dynamics of the model. Numerical simulations show power-law
      distribution of intervals between extinctions, but only for ecosystems with
      sufficient variability of species and with networks of connectivity above certain
      threshold that is very close to the percolation threshold of the network. The
      effect of slow environmental changes on extinction dynamics, degree distribution
      of the network of interspecies interactions, and some emergent properties of our
      model are also examined.

PMID- 15244612
TI  - Combined Monte Carlo and quantum mechanics study of the hydration of the guanine
      cytosine base pair.
AB  - We present a computer simulation study of the hydration of the guanine-cytosine
      (GC) hydrogen-bonded complex. Using first principles density-functional theory,
      with gradient-corrected exchange-correlation and Monte Carlo simulation, we
      include thermal contribution, structural effects, solvent polarization, and the
      water-water and water-GC hydrogen bond interaction to show that the GC
      interaction in an aqueous environment is weakened to about 70% of the value
      obtained for an isolated complex. We also analyze in detail the preferred
      hydration sites of the GC pair and show that on the average it makes around five
      hydrogen bonds with water.

PMID- 15244613
TI  - Diffusion in correlated random potentials, with applications to DNA.
AB  - Many biological processes involve one-dimensional diffusion over a correlated
      inhomogeneous energy landscape with a correlation length xi(c). Typical examples
      are specific protein target location on DNA, nucleosome repositioning, or DNA
      translocation through a nanopore, in all cases with xi(c) approximately 10 nm. We
      investigate such transport processes by the mean first passage time (MFPT)
      formalism, and find diffusion times which exhibit strong sample to sample
      fluctuations. For a displacement N, the average MFPT is diffusive, while its
      standard deviation over the ensemble of energy profiles scales as N(3/2) with a
      large prefactor. Fluctuations are thus dominant for displacements smaller than a
      characteristic N(c) >> xi(c) : typical values are much less than the mean, and
      governed by an anomalous diffusion rule. Potential biological consequences of
      such random walks, composed of rapid scans in the vicinity of favorable energy
      valleys and occasional jumps to further valleys, is discussed.

PMID- 15244614
TI  - Replica model for an unusual directed polymer in 1+1 dimensions and prediction of
      the extremal parameter of gapped sequence alignment statistics.
AB  - Sequence alignment is one of the most important bioinformatics tools for modern
      molecular biology. The statistical characterization of gapped alignment scores
      has been a long-standing problem in sequence alignment research. In this paper,
      we provide a self-contained exposition of sequence alignment, a short review
      about how this problem is related to the directed polymer problem in statistical
      physics, and some analytical results that can be used for predicting alignment
      score statistics. Basically, we present two classes of solutions for the gapped
      alignment statistics by explicitly calculating the evolution of the few-replica
      partition function in 1+1 dimensions. We have obtained the conditions under which
      the more important extremal parameter lambda, characterizing the alignment score
      statistics, becomes predictable.

PMID- 15244615
TI  - Non-Euclidean properties of spike train metric spaces.
AB  - Quantifying the dissimilarity (or distance) between two sequences is essential to
      the study of action potential (spike) trains in neuroscience and genetic
      sequences in molecular biology. In neuroscience, traditional methods for sequence
      comparisons rely on techniques appropriate for multivariate data, which typically
      assume that the space of sequences is intrinsically Euclidean. More recently,
      metrics that do not make this assumption have been introduced for comparison of
      neural activity patterns. These metrics have a formal resemblance to those used
      in the comparison of genetic sequences. Yet the relationship between such metrics
      and the traditional Euclidean distances has remained unclear. We show, both
      analytically and computationally, that the geometries associated with metric
      spaces of event sequences are intrinsically non-Euclidean. Our results
      demonstrate that metric spaces enrich the study of neural activity patterns,
      since accounting for perceptual spaces requires a non-Euclidean geometry.

PMID- 15244616
TI  - Soft Listeria: actin-based propulsion of liquid drops.
AB  - We study the motion of oil drops propelled by actin polymerization in cell
      extracts. Drops deform and acquire a pearlike shape under the action of the
      elastic stresses exerted by the actin comet, a tail of cross-linked actin
      filaments. We solve this free boundary problem and calculate the drop shape
      taking into account the elasticity of the actin gel and the variation of the
      polymerization velocity with normal stress. The pressure balance on the liquid
      drop imposes a zero propulsive force if gradients in surface tension or internal
      pressure are not taken into account. Quantitative parameters of actin
      polymerization are obtained by fitting theory to experiment.

PMID- 15244617
TI  - Statistical mechanics of double-helical polymers.
AB  - We introduce a simple geometric model for a double-stranded and double-helical
      polymer. We study the statistical mechanics of such polymers using both
      analytical techniques and simulations. Our model has a single energy scale which
      determines both the bending and twisting rigidity of the polymer. The helix melts
      at a particular temperature T(c) below which the chain has a helical structure
      and above which this structure is disordered. Under extension we find that for
      small forces, the behavior is very similar to wormlike chain behavior but becomes
      very different at higher forces.

PMID- 15244618
TI  - Unzipping of DNA with correlated base sequence.
AB  - We consider force-induced unzipping transition for a heterogeneous DNA model with
      a correlated base sequence. Both finite-range and long-range correlated
      situations are considered. It is shown that finite-range correlations increase
      stability of DNA with respect to the external unzipping force. Due to long-range
      correlations the number of unzipped base pairs displays two widely different
      scenarios depending on the details of the base sequence: either there is no
      unzipping phase transition at all, or the transition is realized via a sequence
      of jumps with magnitude comparable to the size of the system. Both scenarios are
      different from the behavior of the average number of unzipped base pairs (non
      self-averaging). The results can be relevant for explaining the biological
      purpose of correlated structures in DNA.

PMID- 15244619
TI  - Host-parasite coevolution and optimal mutation rates for semiconservative
      quasispecies.
AB  - In this paper, we extend a model of host-parasite coevolution to incorporate the
      semiconservative nature of DNA replication for both the host and the parasite. We
      find that the optimal mutation rate for the semiconservative and conservative
      hosts converge for realistic genome lengths, thus maintaining the admirable
      agreement between theory and experiment found previously for the conservative
      model and justifying the conservative approximation in some cases. We demonstrate
      that, while the optimal mutation rate for a conservative and semiconservative
      parasite interacting with a given immune system is similar to that of a
      conservative parasite, the properties away from this optimum differ
      significantly. We suspect that this difference, coupled with the requirement that
      a parasite optimize survival in a range of viable hosts, may help explain why
      semiconservative viruses are known to have significantly lower mutation rates
      than their conservative counterparts.

PMID- 15244620
TI  - Hydrodynamic interactions between rotating helices.
AB  - Escherichia coli bacteria use rotating helical flagella to swim. At this scale,
      viscous effects dominate inertia, and there are significant hydrodynamic
      interactions between nearby helices. These interactions cause the flagella to
      bundle during the "runs" of bacterial chemotaxis. Here we use slender-body theory
      to solve for the flow fields generated by rigid helices rotated by stationary
      motors. We determine how the hydrodynamic forces and torques depend on phase and
      phase difference, show that rigid helices driven at constant torque do not
      synchronize, and solve for the flows. We also use symmetry arguments based on
      kinematic reversibility to show that for two rigid helices rotating with zero
      phase difference, there is no time-averaged attractive or repulsive force between
      the helices.

PMID- 15244621
TI  - Random walks of molecular motors arising from diffusional encounters with
      immobilized filaments.
AB  - Movements of molecular motors on cytoskeletal filaments are described by directed
      walks on a line. Detachment from this line is allowed to occur with a small
      probability. Motion in the surrounding fluid is described by symmetric random
      walks. Effects of detachment and reattachment are calculated by an analytical
      solution of the master equation in two and three dimensions. Results are obtained
      for the fraction of bound motors, their average velocity, displacement, and
      dispersion. The analytical results are in good agreement with results from Monte
      Carlo simulations and confirm the behavior predicted by scaling arguments. The
      diffusion coefficient parallel to the filament becomes anomalously large since
      detachment and subsequent reattachment, in the presence of directed motion of the
      bound motors, leads to a broadening of the density distribution. The occurrence
      of protofilaments on a microtubule is modeled by internal states of the binding
      sites. After a transient time, all protofilaments become equally populated.

PMID- 15244622
TI  - Analytical description of finite size effects for RNA secondary structures.
AB  - The ensemble of RNA secondary structures of uniform sequences is studied
      analytically. We calculate the partition function for very long sequences and
      discuss how the crossover length, beyond which asymptotic scaling laws apply,
      depends on thermodynamic parameters. For realistic choices of parameters this
      length can be much longer than natural RNA molecules. This has to be taken into
      account when applying asymptotic theory to interpret experiments or numerical
      results.

PMID- 15244623
TI  - Chain persistency in single-stranded DNA.
AB  - We develop a theoretical approach to hairpin-loop formation of single-stranded
      (ss) DNA by treating the strand as a two-state system in which bases are either
      "stacked" or "unstacked." The looping kinetics of ssDNA is shown to be
      intrinsically different from that of a wormlike chain; it is mainly controlled by
      stacking-breakage probability, not by the mean curvature of loops, and highly
      sensitive to the composition of the loop as seen in recent experiments. Our
      estimate of a stacking energy for poly ( dA ), -3.9 kcal/mol, is consistent with
      known results.

PMID- 15244624
TI  - Analytical analysis of a vesicle tumbling under a shear flow.
AB  - Vesicles under a shear flow exhibit a tank-treading motion of their membrane,
      while their long axis points with an angle <pi/4 with respect to the shear stress
      if the viscosity contrast between the interior and the exterior is not large
      enough. Above a certain viscosity contrast, the vesicle undergoes a tumbling
      bifurcation, a bifurcation which is known for red blood cells. We have recently
      presented the full numerical analysis of this transition. In this paper, we
      introduce an analytical model that has the advantage of being both simple enough
      and capturing the essential features found numerically. The model is based on
      general considerations and does not resort to the explicit computation of the
      full hydrodynamic field inside and outside the vesicle.

PMID- 15244625
TI  - Measure profile surrogates: a method to validate the performance of epileptic
      seizure prediction algorithms.
AB  - In a growing number of publications it is claimed that epileptic seizures can be
      predicted by analyzing the electroencephalogram (EEG) with different
      characterizing measures. However, many of these studies suffer from a severe lack
      of statistical validation. Only rarely are results passed to a statistical test
      and verified against some null hypothesis H0 in order to quantify their
      significance. In this paper we propose a method to statistically validate the
      performance of measures used to predict epileptic seizures. From measure profiles
      rendered by applying a moving-window technique to the electroencephalogram we
      first generate an ensemble of surrogates by a constrained randomization using
      simulated annealing. Subsequently the seizure prediction algorithm is applied to
      the original measure profile and to the surrogates. If detectable changes before
      seizure onset exist, highest performance values should be obtained for the
      original measure profiles and the null hypothesis. "The measure is not suited for
      seizure prediction" can be rejected. We demonstrate our method by applying two
      measures of synchronization to a quasicontinuous EEG recording and by evaluating
      their predictive performance using a straightforward seizure prediction
      statistics. We would like to stress that the proposed method is rather universal
      and can be applied to many other prediction and detection problems.

PMID- 15244626
TI  - Semiconservative replication in the quasispecies model.
AB  - This paper extends Eigen's quasispecies equations to account for the
      semiconservative nature of DNA replication. We solve the equations in the limit
      of infinite sequence length for the simplest case of a static, sharply peaked
      fitness landscape. We show that the error catastrophe occurs when micro, the
      product of sequence length and per base pair mismatch probability, exceeds 2 ln
      [2/ ( 1+1/k ) ], where k>1 is the first-order growth rate constant of the viable
      "master" sequence (with all other sequences having a first-order growth rate
      constant of 1 ). This is in contrast to the result of ln k for conservative
      replication. In particular, as k--> infinity, the error catastrophe is never
      reached for conservative replication, while for semiconservative replication the
      critical micro approaches 2 ln 2. Semiconservative replication is therefore
      considerably less robust than conservative replication to the effect of
      replication errors. We also show that the mean equilibrium fitness of a
      semiconservatively replicating system is given by k ( 2 e(-micro/2) -1 ) below
      the error catastrophe, in contrast to the standard result of k e(-micro) for
      conservative replication (derived by Kimura and Maruyama in 1966). From this
      result it is readily shown that semiconservative replication is necessary to
      account for the observation that, at sufficiently high mutagen concentrations,
      faster replicating cells will die more quickly than more slowly replicating
      cells. Thus, in contrast to Eigen's original model, the semiconservative
      quasispecies equations are able to provide a mathematical basis for explaining
      the efficacy of mutagens as chemotherapeutic agents.

PMID- 15244627
TI  - Pattern formation and nonlocal logistic growth.
AB  - Logistic growth process with nonlocal interactions is considered in one
      dimension. Spontaneous breakdown of translational invariance is shown to take
      place at some parameter region, and the bifurcation regime is identified for
      short and long-range interactions. Domain walls between regions of different
      order parameter are expressed as soliton solutions of the reduced dynamics for
      nearest-neighbor interactions. The analytic results are confirmed by numerical
      simulations.

PMID- 15244628
TI  - Transition path sampling study of flip-flop transitions in model lipid bilayer
      membranes.
AB  - The microscopic dynamics of lipids in biomembranes is of special relevance in the
      study of chemical reactions produced in cells. The mechanism of the exchange of a
      model lipid molecule between both sides of a flexible bilayer membrane or flip
      flop in an aqueous environment has been studied by computer simulation using the
      recently developed transition path sampling technique, since flip-flop
      transitions are infrequent events of the lipid dynamics. In addition, structural
      changes in the membrane have been investigated at ambient conditions and for
      increasing temperature. Our results highlight the cooperative effort of the whole
      system in order to allow a lipid molecule to cross the bottleneck in
      configuration space associated with the transition state of the flip-flop event.
      Within the time interval of the transition, all molecules of the system
      significantly change the frequency of their molecular motions.

PMID- 15244629
TI  - Electrostatic contribution to twist rigidity of DNA.
AB  - The electrostatic contribution to the twist rigidity of DNA is studied, and it is
      shown that the Coulomb self-energy of the double-helical sugar-phosphate backbone
      makes a considerable contribution-the electrostatic twist rigidity of DNA is
      found to be C(elec) approximately 5 nm, which makes up about 7% of its total
      twist rigidity ( C(DNA) approximately 75 nm). The electrostatic twist rigidity is
      found, however, to depend only weakly on the salt concentration, because of a
      competition between two different screening mechanisms: (1) Debye screening by
      the salt ions in the bulk, and (2) structural screening by the periodic charge
      distribution along the backbone of the helical polyelectrolyte. It is found that,
      depending on the parameters, the electrostatic contribution to the twist rigidity
      could stabilize or destabilize the structure of a helical polyelectrolyte.

PMID- 15244630
TI  - Effect of chain connectivity on the structure of Lennard-Jones liquid and its
      implicationon statistical potentials for protein folding.
AB  - Statistical contact potentials and bead-spring models have been widely used for
      computational studies of protein folding. However, there has been speculation
      that systematic error may arise in the contact energy calculations when the
      statistical potentials are deduced under the assumption that the chain
      connectivity in proteins can be ignored. To address this issue, we have performed
      molecular-dynamics simulations to study the structure and dynamics of a simple
      liquid system in which the beads are either connected or unconnected with
      springs. Results from the present study provide useful information for assessing
      the accuracy of the statistical potentials for protein structure simulations.

PMID- 15244631
TI  - Diffusion of actin filaments within a thin layer between two walls.
AB  - Diffusion of the protein filaments F -actin confined in a thin layer between two
      walls is studied using the methods of single filament fluorescence imaging and
      particle tracking. The translational and rotational diffusion coefficients are
      measured for F -actin of lengths in the range of 1.5-5 microm. The length
      dependence of the measured diffusion coefficients is consistent with the
      predicted two-dimensional projection of the diffusion of a cylinder in an
      unbounded fluid. Fits based on the formulas for diffusion in the bulk fluid yield
      higher apparent viscosity values than that of the buffer solution by a factor of
      2 for a layer thickness between 0.7 and 1.6 microm. We show that the measured
      results can be accounted for by correction based on the hydrodynamic theory of a
      long cylinder between confining walls.

PMID- 15244632
TI  - Rupture of a liposomal vesicle.
AB  - We discuss pore dynamics in osmotically stressed vesicles. A set of equations
      which govern the liposomal size, internal solute concentration, and pore diameter
      is solved numerically. We find that dependent on the internal solute
      concentration and vesicle size, liposomes can stay pore free, nucleate a short
      lived pore, or nucleate a long-lived pore. The phase diagram of pore stability is
      constructed, and the different scaling regimes are deduced analytically.

PMID- 15244633
TI  - Phase shifts of synchronized oscillators and the systolic-diastolic blood
      pressure relation.
AB  - We study the phase-synchronization properties of systolic and diastolic arterial
      pressure in healthy subjects. We find that delays in the oscillatory components
      of the time series depend on the frequency bands that are considered, in
      particular we find a change of sign in the phase shift going from the very low
      frequency band to the high frequency band. This behavior should reflect a
      collective behavior of a system of nonlinear interacting elementary oscillators.
      We prove that some models describing such systems, e.g., the Winfree and the
      Kuramoto models, offer a clue to this phenomenon. For these theoretical models
      there is a linear relationship between phase shifts and the difference of natural
      frequencies of oscillators and a change of sign in the phase shift naturally
      emerges.

PMID- 15244634
TI  - Solvent-induced micelle formation in a hydrophobic interaction model.
AB  - We investigate the aggregation of amphiphilic molecules by adapting the two-state
      Muller-Lee-Graziano model for water, in which a solvent-induced hydrophobic
      interaction is included implicitly. We study the formation of various types of
      micelle as a function of the distribution of hydrophobic regions at the molecular
      surface. Successive substitution of nonpolar surfaces by polar ones demonstrates
      the influence of hydrophobicity on the upper and lower critical solution
      temperatures. Aggregates of lipid molecules, described by a refinement of the
      model in which a hydrophobic tail of variable length interacts with different
      numbers of water molecules, are stabilized as the length of the tail increases.
      We demonstrate that the essential features of micelle formation are primarily
      solvent-induced, and are explained within a model which focuses only on the
      alteration of water structure in the vicinity of the hydrophobic surface regions
      of amphiphiles in solution.

PMID- 15244635
TI  - Non-Markovian rotating unstable processes driven by Gaussian colored noise.
AB  - In this paper the statistical properties of the mean passage time distribution
      are used to characterize the decay process of non-Markovian rotating unstable
      processes driven by Gaussian colored noise and subjected to the influence of a
      constant external force. The time characterization will be linear and studied in
      two limiting cases: large and intermediate times. General systems of two
      variables are studied. In both schemes we show that, for small correlation time
      of the noise, the non-Markovian effects are taken into account by an effective
      noise intensity. To compare qualitatively the non-Markovian time scale with
      respect to the Markovian case, we apply those results to determine the detection
      bandwidth of a large external signal in a laser system.

PMID- 15244636
TI  - Simple model for nonexponential relaxation in complex dynamics.
AB  - The nonexponential relaxation occurring in complex dynamics manifested in a wide
      variety of systems is analyzed through a simple model of diffusion in phase
      space. It is found that the inability of the system to find its equilibrium state
      in any time scale becomes apparent in an effective temperature field, which leads
      to a hierarchy of relaxation times responsible for the slow relaxation phenomena.

PMID- 15244637
TI  - Simple jumping process with memory: transport equation and diffusion.
AB  - We present a stochastic jumping process, defined in terms of jump-size
      probability density and jumping rate, which is a generalization of the well-known
      kangaroo process. The definition takes into account two process values: after and
      before the jump. Therefore, the process is able to preserve memory about its
      previous values. It possesses a simple stationary limit. Its master equation is
      interpreted as the kinetic equation with variable collision rate. The process can
      be easily applied to model systems which relax to distributions other than
      Maxwellian. The case of a constant jumping rate corresponds to the diffusion
      process, either normal or ballistic.

PMID- 15244638
TI  - Rejection properties of stochastic-resonance-based detectors of weak harmonic
      signals.
AB  - In [Phys. Rev. E 57, 6470 (1998)]] a thorough characterization in terms of
      receiver operating characteristics of stochastic-resonance detectors of weak
      harmonic signals of known frequency in additive Gaussian noise was given. It was
      shown that strobed sign-counting based strategies can be used to achieve a nice
      trade-off between performance and cost, by comparison with noncoherent
      correlators. Here we discuss the more realistic case where besides the sought
      signal (whose frequency is assumed known) further unwanted spectrally nearby
      signals with comparable amplitude are present. Rejection properties are discussed
      in terms of suitably defined false-alarm and false-dismissal probabilities for
      various values of interfering signal(s) strength and spectral separation.

PMID- 15244639
TI  - Roughness of a tilted anharmonic string at depinning.
AB  - We consider the discretized model of a driven string with an anharmonic elastic
      energy, in a two-dimensional random potential, as introduced by [Phys. Rev. Lett.
      87, 187002 (2001)]]. Using finite size scaling, we numerically compute the
      roughness of the string in a uniform applied force at the critical depinning
      threshold. By considering a string with a net average tilt, we demonstrate that
      the anharmonic elastic energy crosses the model over to the quenched KPZ
      universality class, in agreement with recent theoretical predictions.

PMID- 15244640
TI  - Phase separation in model polydisperse ferrofluids.
AB  - The influence of polydispersity on the phase equilibrium properties of a dipolar
      system with additional short-range (repulsive+attractive) interactions (modeled
      by a shifted Lennard-Jones pair potential) is studied by means of Gibbs ensemble
      Monte Carlo simulations. The critical temperature and density as well as the
      magnetization at the critical point are calculated as a function of the applied
      magnetic field, and the obtained results are compared with the data determined in
      a monodisperse equivalent of the system.

PMID- 15244641
TI  - Hydrodynamic properties of carbon nanotubes.
AB  - We study water flowing past an array of single walled carbon nanotubes using
      nonequilibrium molecular dynamics simulations. For carbon nanotubes mounted with
      a tube spacing of 16.4 x 16.4 nm and diameters of 1.25 and 2.50 nm, respectively,
      we find drag coefficients in reasonable agreement with the macroscopic, Stokes
      Oseen solution. The slip length is -0.11 nm for the 1.25 nm carbon nanotube, and
      0.49 for the 2.50 nm tube for a flow speed of 50 m/s, respectively, and 0.28 nm
      for the 2.50 nm tube at 200 m/s. A slanted flow configuration with a stream- and
      spanwise velocity component of 100 ms(-1) recovers the two-dimensional results,
      but exhibits a significant 88 nm slip along the axis of the tube. These results
      indicate that slip depends on the particular flow configuration.

PMID- 15244642
TI  - Atomic packing of the inherent structure of simple liquids.
AB  - We report a universal inherent packing structure underlying the simple liquids,
      the normalized distribution functions of which are independent of temperature and
      density. The inherent packing state, carrying the maximized configurational
      entropy, has intrinsic connections with the maximally random jammed state of hard
      spheres.

PMID- 15244643
TI  - Thermodynamical scaling of the glass transition dynamics.
AB  - Classification of glass-forming liquids based on the dramatic change in their
      properties upon approach to the glassy state is appealing, since this is the most
      conspicuous and often-studied aspect of the glass transition. Herein, we show
      that a generalized scaling, log (tau) proportional, variant T-1 V-gamma, where
      gamma is a material constant, yields superpositioning for ten glass formers,
      encompassing van der Waals molecules, associated liquids, and polymers. The
      exponent gamma reflects the degree to which volume governs the temperature and
      pressure dependence of the relaxation times.

PMID- 15244644
TI  - Nematic-isotropic phase transition in diblock fused-sphere chain fluids.
AB  - A density-functional theory for the isotropic-nematic phase transition in fluids
      of rigid or semiflexible fused hard-sphere chains, developed previously by the
      authors, is extended to diblock chains each consisting of both a rigid and a
      flexible part. The theory is compared with recent Monte Carlo simulation results
      of McBride et al. The theoretical results for the variation of pressure and
      nematic order parameter with density agree well with the simulation data over
      density ranges where the simulations find isotropic and nematic phases.

PMID- 15244645
TI  - Dependence of threshold behavior upon surface distribution of polymer chains in a
      twisted nematic liquid crystal.
AB  - On the basis of a general Rapini and Papoular equation and a unified surface
      anchoring energy theory, dependence of the threshold behavior of the liquid
      crystal director upon the statistical distribution of polyimide chains is
      theoretically investigated for a twisted nematic liquid crystal cell. We assumed
      that the anisotropy distribution of polyimide chains induced by the rubbing can
      be dominated by a Gaussian distribution around the rubbing direction. Our results
      show that the threshold behavior of a twisted nematic liquid crystal is affected
      strongly by the surface distribution of polymer chains.

PMID- 15244646
TI  - Simple swimmer at low Reynolds number: three linked spheres.
AB  - We propose a very simple one-dimensional swimmer consisting of three spheres that
      are linked by rigid rods whose lengths can change between two values. With a
      periodic motion in a nonreciprocal fashion, which breaks the time-reversal
      symmetry as well as the translational symmetry, we show that the model device can
      swim at low Reynolds number. This model system could be used in constructing
      molecular-sized machines.

PMID- 15244647
TI  - Comment on "Diffusion of epicenters of earthquake aftershocks, Omori's law, and
      generalized continuous-time random walk models".
AB  - Modeling of earthquake sequences using an epidemic-type aftershock sequence model
      by Phys. Rev. E 66, 061104 (2002)] has led these authors to conclude that
      previous analyses of apparent earthquake diffusions were flawed. We show here
      that diffusion analyses based on spatiotemporal correlation measures for
      earthquake populations are an appropriate method for capturing the space-time
      coupling present in earthquake triggering processes.

PMID- 15244649
TI  - Eigenvalue density of correlated complex random Wishart matrices.
AB  - Using a character expansion method, we calculate exactly the eigenvalue density
      of random matrices of the form M dagger M where M is a complex matrix drawn from
      a normalized distribution P(M) approximately exp(-Tr [AMB M dagger]) with A and B
      positive definite (square) matrices of arbitrary dimensions. Such so-called
      correlated Wishart matrices occur in many fields ranging from information theory
      to multivariate analysis.

PMID- 15244650
TI  - Coevolution of dynamical states and interactions in dynamic networks.
AB  - We explore the coupled dynamics of the internal states of a set of interacting
      elements and the network of interactions among them. Interactions are modeled by
      a spatial game and the network of interaction links evolves adapting to the
      outcome of the game. As an example, we consider a model of cooperation in which
      the adaptation is shown to facilitate the formation of a hierarchical interaction
      network that sustains a highly cooperative stationary state. The resulting
      network has the characteristics of a small world network when a mechanism of
      local neighbor selection is introduced in the adaptive network dynamics. The
      highly connected nodes in the hierarchical structure of the network play a
      leading role in the stability of the network. Perturbations acting on the state
      of these special nodes trigger global avalanches leading to complete network
      reorganization.

PMID- 15244651
TI  - Universal behavior of the coefficients of the continuous equation in competitive
      growth models.
AB  - The competitive growth models (CGM) involving only one kind of particles, are a
      mixture of two processes, one with probability p and the other with probability 1
      p. The p dependence produce crossovers between two different regimes. We
      demonstrate that the coefficients of the continuous equation, describing their
      universality classes, are quadratic in p (or 1-p ). We show that the origin of
      such dependence is the existence of two different average time rates. Thus, the
      quadratic p dependence is a universal behavior of all the (CGM). We derive
      analytically the continuous equations for two CGM, in 1+1 dimensions, from the
      microscopic rules using a regularization procedure. We propose generalized
      scalings that reproduce the scaling behavior in each regime. In order to verify
      the analytic results and the scalings, we perform numerical integrations of the
      derived analytical equations. The results are in excellent agreement with those
      of the microscopic CGM presented here and with the proposed scalings.

PMID- 15244652
TI  - Extreme fluctuations in small-world networks with relaxational dynamics.
AB  - We study the distribution and scaling of the extreme height fluctuations for
      Edwards-Wilkinson-type relaxation on small-world substrates. When random links
      are added to a one-dimensional lattice, the average size of the fluctuations
      becomes finite (synchronized state) and the extreme height diverges only
      logarithmically in the large system-size limit. This latter property ensures
      synchronization in a practical sense in small-world coupled multi-component
      autonomous systems. The statistics of the extreme heights is governed by the
      Fisher-Tippett-Gumbel distribution.

PMID- 15244653
TI  - Percolation transition in a two-dimensional system of Ni granular ferromagnets.
AB  - We model magnetotransport features of the quenched condensed granular Ni thin
      films by a random two-dimensional resistor network in order to test the condition
      where a single bond dominates the system. The hopping conductivity is assumed to
      depend on the distance between neighboring ferromagnetic grains and the mutual
      orientation of the magnetic moments of these grains. We find that the quantity
      characterizing the transition from weak disorder (not sensitive to a change of a
      single bond resistivity) to strong disorder (very sensitive to such changes)
      scales as kappa/L(1/1.3), where L is the size of the system and kappa is a
      measure of disorder.

PMID- 15244654
TI  - Coexistence of stable particle and hole solutions for fixed parameter values in a
      simple reaction diffusion system.
AB  - We present a simple autocatalytic reaction-diffusion model for two variables,
      which shows for fixed parameter values the simultaneous stable coexistence of
      particle solutions as well of two types of hole solutions. The associated
      spatially homogeneous system is characterized by the coexistence of one stable
      fixed point and a stable limit cycle solution. We compare our results to other
      dissipative systems which have for fixed parameters either stable particle or
      stable hole solutions including the quintic complex Ginzburg-Landau equation and
      the envelope equation for optical bistability as well as other reaction-diffusion
      models.

PMID- 15244655
TI  - Bifurcation of conical magnetic field.
AB  - A strong magnetic field develops via bifurcation in a flow with accretion, as
      analytical and numerical solutions of magnetohydrodynamic equations show.
      Examples are swirl-free and swirling jets, and thermal convection near a point
      source of heat and gravity. The features of the resulting conical similarity
      magnetic flows are analogous to those observed in cosmic jets.

PMID- 15244656
TI  - Collective modes of quasi-two-dimensional Yukawa liquids.
AB  - Particles in dusty plasmas are often confined to a quasi-two-dimensional
      arrangement. In such layers--besides the formation of compressional and (in
      plane) shear waves--an additional collective excitation may also show up, as
      small-amplitude oscillations of the particles perpendicular to the plane are also
      possible. We explore through molecular dynamics simulations the properties
      (fluctuation spectra, dispersion relation, Einstein frequency) of this out-of
      plane transverse mode in the strongly coupled liquid phase of Yukawa systems.

PMID- 15244657
TI  - Alfven limit in fast ignition.
AB  - Fast ignition inertial confinement fusion relies on rapidly heating the
      compressed fuel to ignition using a laser-generated electron beam. The current
      required far exceeds the Alfven limit, so it can only propagate while the plasma
      provides a nearly coincident return current. The resistive decay of the return
      current is shown to be too rapid for the originally proposed scheme to work.
      Possible solutions to this problem are to increase the mean energy of the beam,
      to heat the fuel to a higher temperature by lowering the beam radius and
      duration, to use multiple beams, and to use an annular beam. Considering the
      laser wavelength required shows that increasing the mean energy and number of
      beams are the most practical solutions.

PMID- 15244658
TI  - Boosted propagation of femtosecond filaments in air by double-pulse combination.
AB  - Two femtosecond pulses in convergent geometry are combined with an appropriate
      time delay, in order to double the length of the plasma channel created by
      multiphoton ionization of air. Suitable parameters are estimated analytically and
      tested by direct numerical simulations.

PMID- 15244659
TI  - Least-squares finite-element lattice Boltzmann method.
AB  - A new numerical model of the lattice Boltzmann method utilizing least-squares
      finite element in space and Crank-Nicolson method in time is presented. The new
      method is able to solve problem domains that contain complex or irregular
      geometric boundaries by using finite-element method's geometric flexibility and
      numerical stability, while employing efficient and accurate least-squares
      optimization. For the pure advection equation on a uniform mesh, the proposed
      method provides for fourth-order accuracy in space and second-order accuracy in
      time, with unconditional stability in the time domain. Accurate numerical results
      are presented through two-dimensional incompressible Poiseuille flow and Couette
      flow.

PMID- 15244660
TI  - Lattice kinetic simulations in three-dimensional magnetohydrodynamics.
AB  - A lattice kinetic algorithm to simulate three-dimensional (3D) incompressible
      magnetohydrodynamics is presented. The fluid is monitored by a distribution
      function, which obeys a scalar kinetic equation, subject to an external force due
      to the imposed magnetic field. Following the work of J. Comput. Phys. 179, 95
      (2002)], the magnetic field is represented by a different three-component vector
      distribution function, which obeys a corresponding vector kinetic equation.
      Discretization of the 3D phase space is based on a 19-bit scheme for the
      hydrodynamic part and on a 7-bit scheme for the magnetic part. Numerical results
      for magnetohydrodynamic (MHD) flow in a rectangular duct with insulating and
      conducting walls provide excellent agreement with corresponding analytical
      solutions. The scheme maintains in all cases tested the MHD constraint inverted
      Delta.B=0 within machine round-off error.

PMID- 15244661
TI  - Violation of the Widom scaling law for effective crossover exponents.
AB  - In this work we consider the universal crossover behavior of two nonequilibrium
      systems exhibiting a continuous phase transition. Focusing on the field driven
      crossover from mean-field to non-mean-field scaling behavior we show that the
      well-known Widom scaling law is violated for the effective exponents in the so
      called crossover regime.

PMID- 15244662
TI  - Dynamics and asymptotical behavior of spreading processes in a closed system.
AB  - We construct differential-integrative equations to investigate the effects of
      different distributions for the incubation period, defined as the period between
      receiving of the message and the beginning of the active state, and for the
      active period, the length of the active state, on the spreading dynamics in a
      closed system where one member can be dynamically linked to any other with given
      probability. The evolution of the ensemble-averaged infected rate gamma(t) is
      calculated by solving the equations for various distribution functions. Both the
      short-term oscillations and long-term saturation crucially depend on the form and
      parameters of the distribution functions. The obtained results may provide
      insights into the characteristics of oscillations and a prognosis of a spreading
      process in closed system.

PMID- 15244663
TI  - Dynamic scaling of fronts in the quantum XX chain.
AB  - The dynamics of the transverse magnetization in the zero-temperature XX chain is
      studied with emphasis on fronts emerging from steplike initial magnetization
      profiles. The fronts move with fixed velocity and display a staircase like
      internal structure whose dynamic scaling is explored both analytically and
      numerically. The front region is found to spread with time subdiffusively with
      the height and the width of the staircase steps scaling as t(-1/3) and t(1/3),
      respectively. The areas under the steps are independent of time; thus the
      magnetization relaxes in quantized "steps" of spin flips.

PMID- 15244664
TI  - Temporal series analysis approach to spectra of complex networks.
AB  - The spacing of nearest levels of the spectrum of a complex network can be
      regarded as a time series. Joint use of the multifractal detrended fluctuation
      approach (MF-DFA) and diffusion entropy (DE) is employed to extract
      characteristics from this time series. For the Watts-Strogatz small-world model,
      there exists a critical point at rewiring probability P(r) =0.32. For a network
      generated in the range 0< P(r) <0.32, the correlation exponent is in the range of
      1.0-1.64. Above this critical point, all the networks behave similar to that at
      p(r) =1. For the Erdos-Renyi model, the time series behaves like fractional
      Brownian motion noise at p(ER) =1/N. For the growing random network (GRN) model,
      the values of the long-range correlation exponent are in the range of 0.74-0.83.
      For most of the GRN networks the probability distribution function of a
      constructed time series obeys a Gaussian form. In the joint use of MF-DFA and DE,
      the shuffling procedure in DE is essential to obtain a reliable result.

PMID- 15244665
TI  - Behavior of susceptible-infected-susceptible epidemics on heterogeneous networks
      with saturation.
AB  - We investigate saturation effects in susceptible-infected-susceptible models of
      the spread of epidemics in heterogeneous populations. The structure of
      interactions in the population is represented by networks with connectivity
      distribution P(k), including scale-free (SF) networks with power law
      distributions P(k) approximately k(-gamma). Considering cases where the
      transmission of infection between nodes depends on their connectivity, we
      introduce a saturation function C(k) which reduces the infection transmission
      rate lambda across an edge going from a node with high connectivity k. A mean
      field approximation with the neglect of degree-degree correlation then leads to a
      finite threshold lambda(c) >0 for SF networks with 2<gamma</=3. We also find, in
      this approximation, the fraction of infected individuals among those with degree
      k for lambda close to lambda(c). We investigate via computer simulation the
      contact process on a heterogeneous regular lattice and compare the results with
      those obtained from mean-field theory with and without neglect of degree-degree
      correlations.

PMID- 15244666
TI  - Scale-free networks of earthquakes and aftershocks.
AB  - We propose a metric to quantify correlations between earthquakes. The metric
      consists of a product involving the time interval and spatial distance between
      two events, as well as the magnitude of the first one. According to this metric,
      events typically are strongly correlated to only one or a few preceding ones.
      Thus a classification of events as foreshocks, main shocks, or aftershocks
      emerges automatically without imposing predetermined space-time windows. In the
      simplest network construction, each earthquake receives an incoming link from its
      most correlated predecessor. The number of aftershocks for any event, identified
      by its outgoing links, is found to be scale free with exponent gamma=2.0(1). The
      original Omori law with p=1 emerges as a robust feature of seismicity, holding up
      to years even for aftershock sequences initiated by intermediate magnitude
      events. The broad distribution of distances between earthquakes and their linked
      aftershocks suggests that aftershock collection with fixed space windows is not
      appropriate.

PMID- 15244667
TI  - Phase transitions of the Ashkin-Teller model including antiferromagnetic
      interactions on a type of diamond hierarchical lattice.
AB  - Using the real-space renormalization-group transformation, we study the phase
      transitions of the Ashkin-Teller model including the antiferromagnetic
      interactions on a type of diamond hierarchical lattices, of which the number of
      bonds per branch of the generator is odd. The isotropic Ashkin-Teller model and
      the anisotropic one are, respectively, investigated. We find that the phase
      diagram, for the isotropic Ashkin-Teller model, consists of five phases, two of
      which are associated with the partially antiferromagnetic ordering of the system,
      while the phase diagram, for the anisotropic Ashkin-Teller model, contains 11
      phases, six of which are related to the partially antiferromagnetic ordering of
      the system. The correlation length critical exponents and the crossover exponents
      are also calculated.

PMID- 15244668
TI  - Conformal field theory of the Flory model of polymer melting.
AB  - We study the scaling limit of a fully packed loop model in two dimensions, where
      the loops are endowed with a bending rigidity. The scaling limit is described by
      a three-parameter family of conformal field theories, which we characterize via
      its Coulomb-gas representation. One choice for two of the three parameters
      reproduces the critical line of the exactly solvable six-vertex model, while
      another corresponds to the Flory model of polymer melting. Exact central charge
      and critical exponents are calculated for polymer melting in two dimensions.
      Contrary to predictions from mean-field theory we show that polymer melting, as
      described by the Flory model, is continuous. We test our field theoretical
      results against numerical transfer matrix calculations.

PMID- 15244669
TI  - Postcollapse dynamics of self-gravitating Brownian particles and bacterial
      populations.
AB  - We address the postcollapse dynamics of a self-gravitating gas of Brownian
      particles in D dimensions in both canonical and microcanonical ensembles. In the
      canonical ensemble, the postcollapse evolution is marked by the formation of a
      Dirac peak with increasing mass. The density profile outside the peak evolves
      self-similarly with decreasing central density and increasing core radius. In the
      microcanonical ensemble, the postcollapse regime is marked by the formation of a
      "binarylike" structure surrounded by an almost uniform halo with high
      temperature. These results are consistent with thermodynamical predictions in
      astrophysics. We also show that the Smoluchowski-Poisson system describing the
      collapse of self-gravitating Brownian particles in a strong-friction limit is
      isomorphic to a simplified version of the Keller-Segel equations describing the
      chemotactic aggregation of bacterial populations. Therefore, our study has direct
      applications in this biological context.

PMID- 15244670
TI  - Effect of adaptive cruise control systems on traffic flow.
AB  - The flow of traffic composed of vehicles that are equipped with adaptive cruise
      control (ACC) is studied using simulations. The ACC vehicles are modeled by a
      linear dynamical equation that has string stability. In platoons of all ACC
      vehicles, perturbations due to changes in the lead vehicle's velocity do not
      cause jams. Simulations of merging flows near an onramp show that if the total
      incoming rate does not exceed the capacity of the single outgoing lane, free flow
      is maintained. With larger incoming flows, a state closely related to the
      synchronized flow phase found in manually driven vehicular traffic has been
      observed. This state, however, should not be considered congested because the
      flow is maximal for the density. Traffic composed of random sequences of ACC
      vehicles and manual vehicles has also been studied. At high speeds (approximately
      30 m/s ) jamming occurs for concentrations of ACC vehicles of 10% or less. At 20%
      no jams are formed. The formation of jams is sensitive to the sequence of
      vehicles (ACC or manual). At lower speeds (approximately 15 m/s ), no critical
      concentration for complete jam suppression is found. Rather, the average velocity
      in the pseudojam region increases with increasing ACC concentration. Mixing 50%
      ACC vehicles randomly with manually driven vehicles on the primary lane in onramp
      simulations shows only modestly reduced travel times and larger flow rates.

PMID- 15244671
TI  - Numerical study of domain coarsening in anisotropic stripe patterns.
AB  - We study the coarsening of two-dimensional smectic polycrystals characterized by
      grains of oblique stripes with only two possible orientations. For this purpose,
      an anisotropic Swift-Hohenberg equation is solved. For quenches close enough to
      the onset of stripe formation, the average domain size increases with time as
      t(1/2). Further from onset, anisotropic pinning forces similar to Peierls
      stresses in solid crystals slow down defects, and growth becomes anisotropic. In
      a wide range of quench depths, dislocation arrays remain mobile and dislocation
      density roughly decays as t(-1/3), while chevron boundaries are totally pinned.
      We discuss some agreements and disagreements found with recent experimental
      results on the coarsening of anisotropic electroconvection patterns.

PMID- 15244672
TI  - Regularly alternating spin-1/2 anisotropic XY chains: the ground-state and
      thermodynamic properties.
AB  - Using the Jordan-Wigner transformation and continued fractions we calculate
      rigorously the thermodynamic quantities for the spin-1/2 transverse Ising chain
      with periodically varying intersite interactions and/or on-site fields. We
      consider in detail the properties of the chains having a period of the transverse
      field modulation equal to 3. The regularly alternating transverse Ising chain
      exhibits several quantum phase transition points, where the number of transition
      points for a given period of alternation strongly depends on the specific set of
      the Hamiltonian parameters. The critical behavior in most cases is the same as
      for the uniform chain. However, for certain sets of the Hamiltonian parameters
      the critical behavior may be changed and weak singularities in the ground-state
      quantities appear. Due to the regular alternation of the Hamiltonian parameters
      the transverse Ising chain may exhibit plateaulike steps in the zero-temperature
      dependence of the transverse magnetization vs transverse field and many-peak
      temperature profiles of the specific heat. We compare the ground-state properties
      of regularly alternating transverse Ising and transverse XX chains and of
      regularly alternating quantum and classical chains. Making use of the
      corresponding unitary transformations we extend the elaborated approach to the
      study of thermodynamics of regularly alternating spin-1/2 anisotropic XY chains
      without field. We use the exact expression for the ground-state energy of such a
      chain of period 2 to discuss how the exchange interaction anisotropy destroys the
      spin-Peierls dimerized phase.

PMID- 15244673
TI  - Return times of random walk on generalized random graphs.
AB  - Random walks are used for modeling various dynamics in, for example, physical,
      biological, and social contexts. Furthermore, their characteristics provide us
      with useful information on the phase transition and critical phenomena of even
      broader classes of related stochastic models. Abundant results are obtained for
      random walk on simple graphs such as the regular lattices and the Cayley trees.
      However, random walks and related processes on more complex networks, which are
      often more relevant in the real world, are still open issues, possibly yielding
      different characteristics. In this paper, we investigate the return times of
      random walks on random graphs with arbitrary vertex degree distributions. We
      analytically derive the distributions of the return times. The results are
      applied to some types of networks and compared with numerical data.

PMID- 15244674
TI  - Ising model on the edge-dual of random networks.
AB  - We consider the Ising model on the edge dual of uncorrelated random networks with
      arbitrary degree distribution. These networks have a finite clustering in the
      thermodynamic limit. High- and low-temperature expansions of Ising model on the
      edge dual of random networks are derived. A detailed comparison of the critical
      behavior of Ising model on scale free random networks and their edge dual is
      presented.

PMID- 15244675
TI  - Phase transitions in periodically driven macroscopic systems.
AB  - We study the large-time behavior of a class of periodically driven macroscopic
      systems. We find, for a certain range of the parameters of either the system or
      the driving fields, the time-averaged asymptotic behavior effectively is that of
      certain other equilibrium systems. We then illustrate with a few examples how the
      conventional knowledge of the equilibrium systems can be made use of in choosing
      the driving fields to engineer new phases and to induce new phase transitions.

PMID- 15244676
TI  - Role of clustering and gridlike ordering in epidemic spreading.
AB  - The spreading of an epidemic is determined by the connectivity patterns which
      underlie the population. While it has been noted that a virus spreads more easily
      on a network in which global distances are small, it remains a great challenge to
      find approaches that unravel the precise role of local interconnectedness. Such
      topological properties enter very naturally in the framework of our two-time-step
      description, also providing an approach to track a probabilistic system. The
      method is elaborated for SIS-type epidemic processes, leading to a quantitative
      interpretation of the role of loops up to length 4 in the onset of an epidemic.

PMID- 15244677
TI  - Quiescent string dominance parameter F and classification of one-dimensional
      cellular automata.
AB  - The classification of rules may be one of the most fundamental targets in the
      study of cellular automata. In this paper, we propose a method for achieving such
      a classification, in which a new quiescent string dominance parameter F, which is
      orthogonal to lambda, is introduced. For N -neighbor and K -state cellular
      automata, in the region 1/K<lambda<1-1/K, the maximum F corresponds to the class
      III rules, and its minimum, to the class II or class I rules. Therefore,
      transition of the pattern class takes place between them without fail. By using
      lambda and F, the phase diagram of cellular automata is determined in the
      (lambda, F ) plane for five-neighbor and four-state cellular automata. The phase
      diagram indicates that along the F axis, class III rules are distributed in a
      large F region, while class I and class II rules are, in a small F region, and
      class IV rules are found in the overlapping region of class II and III rules.
      These distributions are almost independent of lambda. Along the lambda axis, all
      four pattern classes are found in the region 0.25<lambda<0.75, and no correlation
      between pattern class and lambda parameter is observed.

PMID- 15244678
TI  - Boundary and impurity effects on the entanglement of Heisenberg chains.
AB  - We study entanglement of a pair of qubits and the bipartite entanglement between
      the pair and the rest within open-ended Heisenberg XXX and XY models. The open
      boundary condition leads to strong oscillations of entanglements with a two-site
      period, and the two kinds of entanglements are 180 degrees out of phase with each
      other. The mean pairwise entanglement and ground-state energy per site in the XXX
      model are found to be proportional to each other. We study the effects of a
      single bulk impurity on entanglement, and find that there exist threshold values
      of the relative coupling strength between the impurity and its nearest neighbors,
      after which the impurity becomes pairwise entangled with its nearest neighbors.

PMID- 15244679
TI  - Effective temperature in nonequilibrium steady states of Langevin systems with a
      tilted periodic potential.
AB  - We theoretically study Langevin systems with a tilted periodic potential. It is
      known that the ratio Theta of the diffusion constant D to the differential
      mobility mu(d) is not equal to the temperature of the environment (multiplied by
      the Boltzmann constant), except in the linear response regime, where the
      fluctuation dissipation theorem holds. In order to elucidate the physical meaning
      of Theta far from equilibrium, we analyze a modulated system with a slowly
      varying potential. We derive a large scale description of the probability density
      for the modulated system by use of a perturbation method. The expressions we
      obtain show that Theta plays the role of the temperature in the large scale
      description of the system and that Theta can be determined directly in
      experiments, without measurements of the diffusion constant and the differential
      mobility. Hence the relation D= mu(d) Theta among the independent measurable
      quantities D, mu(d), and Theta can be interpreted as an extension of the Einstein
      relation.

PMID- 15244680
TI  - Resonance overlap, secular effects, and nonintegrability: an approach from
      ensemble theory.
AB  - The time evolution of a classical multiresonance nonintegrable Hamiltonian system
      with few degrees of freedom is analyzed on the ensemble level. Time-dependent
      perturbation analysis is applied to the Liouville equation to determine the most
      secular series for the time evolution of the expectation value of some physical
      observables. In contrast to the so-called lambda(2) t expansion for thermodynamic
      systems, which is well known in nonequilibrium statistical physics, we find a
      square root of lambda t expansion in small nonintegrable systems with few degrees
      of freedom. This asymptotic expansion exists only on the level of ensemble but
      not on the level of trajectories. Moreover, the time symmetry of this expansion
      is broken as in nonequilibrium statistical mechanics. The relation of the
      Chirikov overlapping criterion to our approach is discussed.

PMID- 15244681
TI  - Measure of predictability.
AB  - Many techniques have been developed to measure the difficulty of forecasting data
      from an observed time series. This paper introduces a measure which we call the
      "forecast entropy" designed to measure the predictability of a time series. We
      use attractors reconstructed from the time series and the distributions in the
      regular and tangent spaces of the data which comprise the attractor. We then
      consider these distributions on different scales. We present a formula for
      calculating the forecast entropy. To provide a standard of predictability, we
      define an idealized random system whose forecast entropy will be maximal; we then
      use this measure to rescale the forecast entropy to lie in the range [0,1]. The
      time series obtained from several chaotic systems as well as from a pseudorandom
      system are studied using this measure. We present evidence that the forecast
      entropy can be used as a tool for determining optimal delays and embedding
      dimensions used for reconstructing better attractors. We also show that the
      forecast entropy of a random system has completely different characteristics from
      that of a deterministic one.

PMID- 15244682
TI  - Evolutionary minority game: the roles of response time and mutation threshold.
AB  - In the evolutionary minority game, agents are allowed to evolve their strategies
      ("mutate") based on past experience. We explore the dependence of the system's
      global behavior on the response time and the mutation threshold of the agents. We
      find that the precise values of these parameters determine if the strategy
      distribution of the population has a U shape, inverse U shape, or W shape. It is
      shown that in a free society (market), highly adaptive agents (with short
      response times) perform best. In addition, "patient" agents (with high mutation
      thresholds) outperform "nervous" ones.

PMID- 15244683
TI  - Melting of polydisperse hard disks.
AB  - The melting of a polydisperse hard-disk system is investigated by Monte Carlo
      simulations in the semigrand canonical ensemble. This is done in the context of
      possible continuous melting by a dislocation-unbinding mechanism, as an extension
      of the two-dimensional hard-disk melting problem. We find that while there is
      pronounced fractionation in polydispersity, the apparent density-polydispersity
      gap does not increase in width, contrary to 3D polydisperse hard spheres. The
      point where the Young's modulus is low enough for the dislocation unbinding to
      occur moves with the apparent melting point, but stays within the density gap,
      just like for the monodisperse hard-disk system. Additionally, we find that
      throughout the accessible polydispersity range, the bound dislocation-pair
      concentration is high enough to affect the dislocation-unbinding melting as
      predicted by Kosterlitz, Thouless, Halperin, Nelson, and Young.

PMID- 15244684
TI  - Hard disks in narrow channels.
AB  - The thermodynamic and dynamical behavior of a gas of hard disks in a narrow
      channel is studied theoretically and numerically. Using a virial expansion, we
      find that the pressure and collision frequency curves exhibit a singularity at a
      channel width corresponding to twice the disk diameter. As expected, the maximum
      Lyapunov exponent is also found to display a similar behavior. At high density,
      these curves are dominated by solidlike configurations which are different from
      the bulk ones, due to the channel boundary conditions.

PMID- 15244685
TI  - Stability of vacuum in coupled directed percolation processes.
AB  - We study the absorbing phase transitions in coupled directed percolation (DP)
      processes with N -species particles in one dimension. The interspecies coupling
      is linear, bidirectional, and excitatory. We find that the presence of a
      spontaneous annihilation process A-->0 is essential in stabilizing the absorbing
      phase (vacuum). In the coupled contact processes, the vacuum is stable and the
      system exhibits DP type transitions, regardless of the coupling strength, for all
      N. However, in the coupled branching annihilation random walks with one offspring
      (BAW), where particle annihilations occur only through binary diffusion processes
      A+A-->0, the vacuum becomes unstable with respect to an arbitrarily small
      branching rate in a sufficiently strong coupling regime for N> or =3. The N=2 BAW
      exhibits the DP type transition for any coupling strength, but the inclusion of
      interspecies hard core (HC) interaction makes the vacuum unstable again and the
      system is always active in a strong coupling regime. Critical behavior near the
      zero branching point is characterized by the mean-field scaling exponents, beta=
      nu(radially) = 1/2 and nu(axially) =1, regardless of the presence of HC
      interaction. We also discuss the effects of the asymmetric coupling.

PMID- 15244686
TI  - Statistical mechanics and thermodynamic limit of self-gravitating fermions in D
      dimensions.
AB  - We discuss the statistical mechanics of a system of self-gravitating fermions in
      a space of dimension D. We plot the caloric curves of the self-gravitating Fermi
      gas giving the temperature as a function of energy and investigate the nature of
      phase transitions as a function of the dimension of space. We consider stable
      states (global entropy maxima) as well as metastable states (local entropy
      maxima). We show that for D> or =4, there exists a critical temperature (for
      sufficiently large systems) and a critical energy below which the system cannot
      be found in statistical equilibrium. Therefore, for D> or =4, quantum mechanics
      cannot stabilize matter against gravitational collapse. This is similar to a
      result found by Ehrenfest (1917) at the atomic level for Coulomb forces. This
      makes the dimension D=3 of our Universe very particular with possible
      implications regarding the anthropic principle. Our study joins a long tradition
      of scientific and philosophical papers that examined how the dimension of space
      affects the laws of physics.

PMID- 15244687
TI  - Reinforcing the resilience of complex networks.
AB  - Given a connected network, it can be augmented by applying a growing strategy
      (e.g., random- or preferential-attachment rules) over the previously existing
      structure. Another approach for augmentation, recently introduced, involves
      incorporating a direct edge between any two nodes which are found to be connected
      through at least one self-avoiding path of length L. This work investigates the
      resilience of random- and preferential-attachment models augmented by using the
      three schemes identified above. Considering random- and preferential-attachment
      networks, their giant cluster are identified and reinforced, then the resilience
      of the resulting networks with respect to highest-degree node attack is
      quantified through simulations. Statistical characterization of the effects of
      augmentations over some of the network properties is also provided. The results,
      which indicate that substantial reinforcement of the resilience of complex
      networks can be achieved by the expansions, also confirm the superior robustness
      of the random expansion. An important obtained result is that the initial growth
      scheme was found to have little effect over the possibilities of further
      enhancement of the network by subsequent reinforcement schemes.

PMID- 15244688
TI  - Totally asymmetric exclusion process on chains with a double-chain section in the
      middle: computer simulations and a simple theory.
AB  - Computer simulations of the totally asymmetric simple-exclusion process on chains
      with a double-chain section in the middle are performed in the case of random
      sequential update. The outer ends of the chain segments connected to the middle
      double-chain section are open, so that particles are injected at the left end
      with rate alpha and removed at the right end with rate beta. At the branching
      point of the graph (the left end of the middle section) the particles choose with
      equal probability 1/2 which branch to take and then simultaneous motion of the
      particles along the two branches is simulated. With the aid of a simple theory,
      neglecting correlations at the junctions of the chain segments, the possible
      phase structures of the model are clarified. Density profiles and nearest
      neighbor correlations in the steady states of the model at representative points
      of the phase diagram are obtained and discussed. Cross correlations are found to
      exist between equivalent sites of the branches of the middle section whenever
      they are in a coexistence phase.

PMID- 15244689
TI  - Anisotropic limit of the bond-percolation model and conformal invariance in
      curved geometries.
AB  - We investigate the anisotropic limit of the bond-percolation model in d
      dimensions, which is equivalent to a (d-1) -dimensional quantum q-->1 Potts
      model. We formulate an efficient Monte Carlo method for this model. Its
      application shows that the anisotropic model fits well with the percolation
      universality class in d dimensions. For three-dimensional rectangular geometry,
      we determine the critical point as t(c) =8.6429(4), and determine the length
      ratio as alpha(0) =1.5844(3), which relates the anisotropic limit of the
      percolation model and its isotropic version. On this basis, we simulate critical
      systems in several curved geometries including a spheroid and a spherocylinder.
      Using finite-size scaling and the assumption of conformal invariance, we
      determine the bulk and surface magnetic exponents in two and three dimensions.
      They are in good agreement with the existing results.

PMID- 15244690
TI  - Dynamics of rumor spreading in complex networks.
AB  - We derive the mean-field equations characterizing the dynamics of a rumor process
      that takes place on top of complex heterogeneous networks. These equations are
      solved numerically by means of a stochastic approach. First, we present
      analytical and Monte Carlo calculations for homogeneous networks and compare the
      results with those obtained by the numerical method. Then, we study the spreading
      process in detail for random scale-free networks. The time profiles for several
      quantities are numerically computed, which allows us to distinguish among
      different variants of rumor spreading algorithms. Our conclusions are directed to
      possible applications in replicated database maintenance, peer-to-peer
      communication networks, and social spreading phenomena.

PMID- 15244691
TI  - Random matrix ensembles from nonextensive entropy.
AB  - The classical Gaussian ensembles of random matrices can be constructed by
      maximizing Boltzmann-Gibbs-Shannon's entropy, S(BGS) = -integral
      dH[P(H)]ln[P(H)], with suitable constraints. Here, we construct and analyze
      random-matrix ensembles arising from the generalized entropy S(q) = [1- integral
      dH [P(H)](q)] /(q-1) (thus, S1 = S(BGS) ). The resulting ensembles are
      characterized by a parameter q measuring the degree of nonextensivity of the
      entropic form. Making q-->1 recovers the Gaussian ensembles. If q not equal 1,
      the joint probability distributions P(H) cannot be factorized, i.e., the matrix
      elements of H are correlated. In the limit of large matrices two different
      regimes are observed. When q<1, P(H) has compact support, and the fluctuations
      tend asymptotically to those of the Gaussian ensembles. Anomalies appear for q>1
      : Both P(H) and the marginal distributions P( H(ij) ) show power-law tails.
      Numerical analyses reveal that the nearest-neighbor spacing distribution is also
      long-tailed (not Wigner-Dyson) and, after proper scaling, very close to the
      result for the 2 x 2 case--a generalization of Wigner's surmise. We discuss
      connections of these "nonextensive" ensembles with other non-Gaussian ones, such
      as the so-called Levy ensembles and those arising from soft confinement.

PMID- 15244692
TI  - Experiment, theory, and simulation of the evacuation of a room without
      visibility.
AB  - We study the evacuation process from a smoky room by means of experiments and
      simulations. People in a dark or smoky room are mimicked by "blind" students
      wearing eye masks. The evacuation of the disoriented students from the room is
      observed by video cameras, and the escape time of each student is measured. We
      find that the disoriented students exhibit a distinctly different behavior
      compared to a situation in which people can see their environment. Our
      experimental results are related to a theoretical approach and reproduced by an
      extended lattice gas model taking into account the empirically observed behavior.
      Our particular focus is on the mean value and distribution of escape times. For a
      large number of people in the room, the escape time distribution is wide because
      of jamming. Surprisingly, adding more exits does not improve the situation in the
      expected way, since most people use the exit that is discovered first, which may
      be viewed as a kind of herding effect based on nonlocal, but direct acoustic
      interactions. Moreover, the average escape time becomes minimal for a certain
      finite number of people in the dark or smoky room. These nonlinear effects have
      practical implications for emergency evacuation and the planning of safer
      buildings.

PMID- 15244693
TI  - Fast algorithm for detecting community structure in networks.
AB  - Many networks display community structure--groups of vertices within which
      connections are dense but between which they are sparser--and sensitive computer
      algorithms have in recent years been developed for detecting this structure.
      These algorithms, however, are computationally demanding, which limits their
      application to small networks. Here we describe an algorithm which gives
      excellent results when tested on both computer-generated and real-world networks
      and is much faster, typically thousands of times faster, than previous
      algorithms. We give several example applications, including one to a
      collaboration network of more than 50,000 physicists.

PMID- 15244694
TI  - Driven diffusive systems: how steady states depend on dynamics.
AB  - In contrast to equilibrium systems, nonequilibrium steady states depend
      explicitly on the underlying dynamics. Using Monte Carlo simulations with
      Metropolis, Glauber, and heat bath rates, we illustrate this expectation for an
      Ising lattice gas, driven far from equilibrium by an "electric" field. While heat
      bath and Glauber rates generate essentially identical data for structure factors
      and two-point correlations, Metropolis rates give noticeably weaker correlations,
      as if the "effective" temperature were higher in the latter case. We also measure
      energy histograms and define a simple ratio which is exactly known and closely
      related to the Boltzmann factor for the equilibrium case. For the driven system,
      the ratio probes a thermodynamic derivative which is found to be dependent on
      dynamics.

PMID- 15244695
TI  - Percolation on a multifractal.
AB  - We investigate percolation phenomena in multifractal objects that are built in a
      simple way. In these objects the multifractality comes directly from the
      geometric tiling. We identify some differences between percolation in the
      proposed multifractals and in a regular lattice. There are basically two sources
      of these differences. The first is related to the coordination number, which
      changes along the multifractal. The second comes from the way the weight of each
      cell in the multifractal affects the percolation cluster. We use many samples of
      finite size lattices and draw the histogram of percolating lattices against site
      occupation probability. Depending on a parameter characterizing the multifractal
      and the lattice size, the histogram can have two peaks. We observe that the
      percolation threshold for the multifractal is lower than that for the square
      lattice. We compute the fractal dimension of the percolating cluster and the
      critical exponent beta. Despite the topological differences, we find that the
      percolation in a multifractal support is in the same universality class as
      standard percolation.

PMID- 15244696
TI  - Generalized determinant solution of the discrete-time totally asymmetric
      exclusion process and zero-range process.
AB  - We consider the discrete-time evolution of a finite number of particles obeying
      the totally asymmetric exclusion process with backward-ordered update on an
      infinite chain. Our first result is a determinant expression for the conditional
      probability of finding the particles at given initial and final positions,
      provided that they start and finish simultaneously. The expression has the same
      form as the one obtained by J. Stat. Phys. 88, 427 (1997)] for the continuous
      time process. Next we prove that under some sufficient conditions the determinant
      expression can be generalized to the case when the particles start and finish at
      their own times. The latter result is used to solve a nonstationary zero-range
      process on a finite chain with open boundaries.

PMID- 15244697
TI  - Cooperating attackers in neural cryptography.
AB  - A successful attack strategy in neural cryptography is presented. The neural
      cryptosystem, based on synchronization of neural networks by mutual learning, has
      been recently shown to be secure under different attack strategies. The success
      of the advanced attacker presented here, called the "majority-flipping attacker,"
      does not decay with the parameters of the model. This attacker's outstanding
      success is due to its using a group of attackers which cooperate throughout the
      synchronization process, unlike any other attack strategy known. An analytical
      description of this attack is also presented, and fits the results of
      simulations.

PMID- 15244698
TI  - Estimating mutual information.
AB  - We present two classes of improved estimators for mutual information M(X,Y), from
      samples of random points distributed according to some joint probability density
      mu(x,y). In contrast to conventional estimators based on binnings, they are based
      on entropy estimates from k -nearest neighbor distances. This means that they are
      data efficient (with k=1 we resolve structures down to the smallest possible
      scales), adaptive (the resolution is higher where data are more numerous), and
      have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly
      due to nonuniformity of the density at the smallest resolved scale, giving
      typically systematic errors which scale as functions of k/N for N points.
      Numerically, we find that both families become exact for independent
      distributions, i.e. the estimator M(X,Y) vanishes (up to statistical
      fluctuations) if mu(x,y)=mu(x)mu(y). This holds for all tested marginal
      distributions and for all dimensions of x and y. In addition, we give estimators
      for redundancies between more than two random variables. We compare our
      algorithms in detail with existing algorithms. Finally, we demonstrate the
      usefulness of our estimators for assessing the actual independence of components
      obtained from independent component analysis (ICA), for improving ICA, and for
      estimating the reliability of blind source separation.

PMID- 15244699
TI  - First-order phase transition of fixed connectivity surfaces.
AB  - We report numerical evidence of the discontinuous transition of a tethered
      membrane model which is defined within a framework of the membrane elasticity of
      Helfrich. Two kinds of phantom tethered membrane models are studied via the
      canonical Monte Carlo simulation on triangulated fixed connectivity surfaces of
      spherical topology. One surface model is defined by the Gaussian term and the
      bending energy term, and the other, which is tensionless, is defined by the
      bending energy term and a hard wall potential. The bending energy is defined by
      using the normal vector at each vertex. Both models undergo the first-order phase
      transition characterized by a gap of the bending energy. The phase structure of
      the models depends on the choice of discrete bending energy.

PMID- 15244700
TI  - Absorbing state phase transitions with quenched disorder.
AB  - Quenched disorder--in the sense of the Harris criterion--is generally a relevant
      perturbation at an absorbing state phase transition point. Here using a strong
      disorder renormalization group framework and effective numerical methods we study
      the properties of random fixed points for systems in the directed percolation
      universality class. For strong enough disorder the critical behavior is found to
      be controlled by a strong disorder fixed point, which is isomorph with the fixed
      point of random quantum Ising systems. In this fixed point dynamical correlations
      are logarithmically slow and the static critical exponents are conjecturedly
      exact for one-dimensional systems. The renormalization group scenario is
      confronted with numerical results on the random contact process in one and two
      dimensions and satisfactory agreement is found. For weaker disorder the numerical
      results indicate static critical exponents which vary with the strength of
      disorder, whereas the dynamical correlations are compatible with two possible
      scenarios. Either they follow a power-law decay with a varying dynamical
      exponent, like in random quantum systems, or the dynamical correlations are
      logarithmically slow even for a weak disorder. For models in the parity
      conserving universality class there is no strong disorder fixed point according
      to our renormalization group analysis.

PMID- 15244701
TI  - Derivation of amplitude equations for nonlinear oscillators subject to arbitrary
      forcing.
AB  - By using a generalization of the multiple scales technique we develop a method to
      derive amplitude equations for zero-dimensional forced systems. The method allows
      to consider either additive or multiplicative forcing terms and can be
      straightforwardly applied to the case that the forcing is white noise. We give
      examples of the use of this method to the case of the van der Pol-Duffing
      oscillator. The writing of the amplitude equations in terms of a Lyapunov
      potential allow us to obtain an analytical expression for the probability
      distribution function which reproduces reasonably well the numerical simulation
      results.

PMID- 15244702
TI  - Influence of branch points in the complex plane on the transmission through
      double quantum dots.
AB  - We consider single-channel transmission through a double quantum dot system
      consisting of two single dots that are connected by a wire and coupled each to
      one lead. The system is described in the framework of the S matrix theory by
      using the effective Hamiltonian of the open quantum system. It consists of the
      Hamiltonian of the closed system (without attached leads) and a term that
      accounts for the coupling of the states via the continuum of propagating modes in
      the leads. This model allows one to study the physical meaning of branch points
      in the complex plane. They are points of coalesced eigenvalues and separate the
      two scenarios with avoided level crossings and without any crossings in the
      complex plane. They influence strongly the features of transmission through
      double quantum dots.

PMID- 15244703
TI  - Optical patterns with different wavelengths.
AB  - The semiconductor resonator is an example of an optical system where two
      modulational instabilities with different wave numbers coexist. In the limit of
      nascent bistability, the dynamics is generically described by a nonvariational
      real order parameter equation, of which we give a detailed derivation. This
      considerably simplifies the linear and weakly nonlinear stability analyses. When
      the two instabilities are close together, we derive normal form equations and put
      special emphasis on "envelope" branches of solutions. These particular solutions
      may connect the two instability points or form an isola. On the basis of these
      rigorous results, we finally discuss the case of distant modulational
      instabilities, in both one and two transverse dimensions.

PMID- 15244704
TI  - Continuous control of chaos based on the stability criterion.
AB  - A method of chaos control based on stability criterion is proposed in the present
      paper. This method can stabilize chaotic systems onto a desired periodic orbit by
      a small time-continuous perturbation nonlinear feedback. This method does not
      require linearization of the system around the stabilized orbit and only an
      approximate location of the desired periodic orbit is required which can be
      automatically detected in the control process. The control can be started at any
      moment by choosing appropriate perturbation restriction condition. It seems that
      more flexibility and convenience are the main advantages of this method. The
      discussions on control of attitude motion of a spacecraft, Rossler system, and
      two coupled Duffing oscillators are given as numerical examples.

PMID- 15244705
TI  - Semiclassical approximations based on complex trajectories.
AB  - The semiclassical limit of the coherent state propagator <z" absolute value of e(
      i H T/Planck's over 2 pi) z'> involves complex classical trajectories of the
      Hamiltonian H(u,v) = <v absolute value of H u> satisfying u(0) = z' and v(T) =
      z"*. In this work we study mostly the case z' = z". The propagator is then the
      return probability amplitude of a wave packet. We show that a plot of the exact
      return probability brings out the quantal images of the classical periodic
      orbits. Then we compare the exact return probability with its semiclassical
      approximation for a soft chaotic system with two degrees of freedom. We find two
      situations where classical trajectories satisfying the correct boundary
      conditions must be excluded from the semiclassical formula. The first occurs when
      the contribution of the trajectory to the propagator becomes exponentially large
      as Planck's over 2 pi goes to zero. The second occurs when the contributing
      trajectories undergo bifurcations. Close to the bifurcation the semiclassical
      formula diverges. More interestingly, in the example studied, after the
      bifurcation, where more than one trajectory satisfying the boundary conditions
      exist, only one of them in fact contributes to the semiclassical formula, a
      phenomenon closely related to Stokes lines. When the contributions of these
      trajectories are filtered out, the semiclassical results show excellent agreement
      with the exact calculations.

PMID- 15244706
TI  - Eigenmodes and symmetry selection mechanisms in circular large-aperture vertical
      cavity surface-emitting lasers.
AB  - The characteristics of the spatial eigenmodes of vertical-cavity surface-emitting
      lasers with a large circular aperture are considered close to the lasing
      threshold. Experiments yield patterns based on rotational symmetry ("flowerlike"
      patterns) or on Cartesian symmetry (stripelike patterns) for very close operating
      conditions. The former are compatible with the boundary conditions whereas the
      latter are expected in infinite devices. Theoretically, the problem is considered
      in the framework of an eigenmode analysis of a linear partial differential
      equation for the optical field valid at threshold. This formulation allows for a
      simple implementation of asymmetries due to the reflection properties of Bragg
      mirrors as well as of transverse variations of gain and refractive index due to
      the device structure or due to imperfections in the growth process. A sharp
      transition between flowerlike modes and stripelike modes is shown to occur, if
      the device aperture is increased.

PMID- 15244707
TI  - Pattern formation in diffusive-advective coupled map lattices.
AB  - We investigate pattern formation and evolution in coupled map lattices when
      advection is incorporated, in addition to the usual diffusive term. All patterns
      may be suitably grouped into five classes: three periodic, supporting static
      patterns and traveling waves, and two nonperiodic. Relative frequencies are
      determined as a function of all model parameters: diffusion, advection, local
      nonlinearity, and lattice size. Advection plays an important role in coupled map
      lattices, being capable of considerably altering pattern evolution. For instance,
      advection may induce synchronization, making chaotic patterns evolve
      periodically. As a byproduct we describe a practical algorithm for classifying
      generic pattern evolutions and for measuring velocities of traveling waves.

PMID- 15244708
TI  - Role of complexing agents in the appearance of Turing patterns.
AB  - In this paper we study a four-species reaction-diffusion system where Turing
      patterns are stabilized by the presence of fast reversible reactions between the
      morphogens and two different mobile complexing agents (CAs) that are not
      necessarily in excess. We provide a quantitative explanation of how the
      interaction with the CA changes the size of the Turing space making it possible
      to observe patterns even in a region where the free diffusion coefficients of the
      relevant species are equal, as is usually the case in real systems. Our
      analytical treatment gives a series of mathematical relations that can be helpful
      for those designing experiments where Turing patterns are expected to appear. We
      also show how the mobility of CAs affect the characteristic size of the pattern.
      Finally, we provide an example of biological interest in order to illustrate the
      main procedures and results.

PMID- 15244709
TI  - Three-body dynamics in a (1+1) -dimensional relativistic self-gravitating system.
AB  - The results of our study of the motion of a three particle, self-gravitating
      system in general relativistic lineal gravity is presented for an arbitrary ratio
      of the particle masses. We derive a canonical expression for the Hamiltonian of
      the system and discuss the numerical solution of the resulting equations of
      motion. This solution is compared to the corresponding nonrelativistic and post
      Newtonian approximation solutions so that the dynamics of the fully relativistic
      system can be interpreted as a correction to the one-dimensional Newtonian self
      gravitating system. We find that the structure of the phase space of each of
      these systems yields a large variety of interesting dynamics that can be divided
      into three distinct regions: annulus, pretzel, and chaotic; the first two being
      regions of quasiperiodicity while the latter is a region of chaos. By changing
      the relative masses of the three particles we find that the relative sizes of
      these three phase space regions changes, and that this deformation can be
      interpreted physically in terms of the gravitational interactions of the
      particles. Furthermore, we find that many of the interesting characteristics
      found in the case where all of the particles share the same mass also appear in
      our more general study. We find that there are additional regions of chaos in the
      unequal mass system which are not present in the equal mass case. We compare
      these results to those found in similar systems.

PMID- 15244710
TI  - Consequences of nonlocal connections in networks of chaotic maps under threshold
      activated coupling.
AB  - We study the effects of random nonlocal connections on networks of chaotic maps
      under threshold activated coupling. In threshold regimes where a large number of
      unsynchronized attractors occur under regular connections, we show how nonlocal
      rewirings yield synchronized networks. However, the dependence of the
      synchronized fraction on the fraction of randomized nonlocal links is typically
      nonmonotonic here. Further, the mean time to reach synchronization with respect
      to the fraction of rewiring also indicates an optimum degree of nonlocality for
      which synchronization is most efficiently achieved.

PMID- 15244711
TI  - Onset of synchronization in systems of globally coupled chaotic maps.
AB  - We study the transition to coherence of an ensemble of globally coupled chaotic
      maps allowing for ensembles of nonidentical maps and for noise. The transition
      coupling strength is determined from a kind of transfer function of the
      perturbation evolution. We present analytical results, and we test these results
      using numerical experiments for several large systems consisting of ensembles of
      many coupled maps. The later includes ensembles of identical noiseless maps,
      identical maps subject to noise, and ensembles of nonidentical maps. One of our
      examples suggests that the validity of the perturbation theory approach can be
      problematic for an ensemble of noiseless identical maps if the maps are
      nonhyperbolic. However, for such a case, noise and/or parameter spread seems to
      have a regularizing effect restoring the validity of perturbation theory.

PMID- 15244712
TI  - Experimental control of coherence of a chaotic oscillator.
AB  - We give experimental evidence that a delayed feedback control strategy is able to
      efficiently enhance the coherence of an experimental self-sustained chaotic
      oscillator obtained from a CO2 laser with electro-optical feedback. We
      demonstrate that coherence control is achieved for various choices of the delay
      time in the feedback control, including values that would lead to the
      stabilization of an unstable periodic orbit embedded within the chaotic
      attractor. The relationship between the two processes is discussed.

PMID- 15244713
TI  - Average patterns and coherent phenomena in wide aperture lasers.
AB  - Using a realistic model of wide aperture, weakly astigmatic lasers we develop a
      framework to analyze experimental average intensity patterns. We use the model to
      explain the appearance of patterns in terms of the modes of the cavity and to
      show that the breaking of the symmetry of the average intensity patterns is
      caused by overlaps in the frequency spectra of nonvanishing of modes with
      different parity. This result can be used even in systems with very fast dynamics
      to detect experimentally overlaps of frequency spectra of modes.

PMID- 15244714
TI  - Dislocation dynamics in an anisotropic stripe pattern.
AB  - The dynamics of dislocations confined to grain boundaries in a striped system are
      studied using electroconvection in the nematic liquid crystal N4. In
      electroconvection, a striped pattern of convection rolls forms for sufficiently
      high driving voltages. We consider the case of a rapid change in the voltage that
      takes the system from a uniform state to a state consisting of striped domains
      with two different wave vectors. The domains are separated by domain walls along
      one axis and a grain boundary of dislocations in the perpendicular direction. The
      pattern evolves through dislocation motion parallel to the domain walls. We
      report on features of the dislocation dynamics. The kinetics of the domain motion
      is quantified using three measures: dislocation density, average domain wall
      length, and total domain wall length per area. All three quantities exhibit
      behavior consistent with power-law evolution in time, with the defect density
      decaying as t(-1/3), the average domain wall length growing as t(1/3), and the
      total domain wall length decaying as t(-1/5). The two different exponents are
      indicative of the anisotropic growth of domains in the system.

PMID- 15244715
TI  - Controllability of flow turbulence.
AB  - In this paper, we study the controllability of real-world flow turbulence
      governed by the two-dimensional Navier-Stokes equations, using strategies
      developed in chaos control. A case of control/synchronization of turbulent
      dynamics is observed when only one component of the velocity field vector is
      unidirectionally coupled to a target state, while the other component is
      uncoupled. Unlike previous results, it is shown that the dynamics of the whole
      velocity field cannot be completely controlled/synchronized to the target, even
      in the limit of long time and strong coupling strength. It is further revealed
      that the controlled component of the velocity field can be fully
      controlled/synchronized to the target, but the other component, which is not
      directly coupled to the target, can only be partially controlled/synchronized to
      the target. By extending an auxiliary method to distributed dynamic systems, the
      partial synchronization of two turbulent orbits in the present study can be
      categorized in the domain of generalized synchronization of spatiotemporal
      dynamics.

PMID- 15244716
TI  - Spatial patterns of desynchronization bursts in networks.
AB  - We adapt a previous model and analysis method (the master stability function),
      extensively used for studying the stability of the synchronous state of networks
      of identical chaotic oscillators, to the case of oscillators that are similar but
      not exactly identical. We find that bubbling induced desynchronization bursts
      occur for some parameter values. These bursts have spatial patterns, which can be
      predicted from the network connectivity matrix and the unstable periodic orbits
      embedded in the attractor. We test the analysis of bursts by comparison with
      numerical experiments. In the case that no bursting occurs, we discuss the
      deviations from the exactly synchronous state caused by the mismatch between
      oscillators.

PMID- 15244717
TI  - Classical intermittency and the quantum Anderson transition.
AB  - We investigate the properties of quantum systems whose classical counterpart
      presents intermittency. It is shown, by using recent semiclassical techniques,
      that the quantum spectral correlations of such systems are expressed in terms of
      the eigenvalues of an anomalous diffusion operator. For certain values of the
      parameters leading to ballistic diffusion and 1/f noise the spectral properties
      of our model show similarities with those of a disordered system at the Anderson
      transition. In Hamiltonian systems, intermittency is closely related to the
      presence of cantori in the classical phase space. We suggest, based on this
      relation, that our findings may be relevant for the description of the spectral
      correlations of Hamiltonians with a classical phase space homogeneously filled by
      cantori. Finally we discuss the extension of our results to higher dimensions and
      their relation to Anderson models with long-range hopping.

PMID- 15244718
TI  - Resonance tongues and patterns in periodically forced reaction-diffusion systems.
AB  - Various resonant and near-resonant patterns form in a light-sensitive Belousov
      Zhabotinsky (BZ) reaction in response to a spatially homogeneous time-periodic
      perturbation with light. The regions (tongues) in the forcing frequency and
      forcing amplitude parameter plane where resonant patterns form are identified
      through analysis of the temporal response of the patterns. Resonant and near
      resonant responses are distinguished. The unforced BZ reaction shows both
      spatially uniform oscillations and rotating spiral waves, while the forced system
      shows patterns such as standing-wave labyrinths and rotating spiral waves. The
      patterns depend on the amplitude and frequency of the perturbation, and also on
      whether the system responds to the forcing near the uniform oscillation frequency
      or the spiral wave frequency. Numerical simulations of a forced FitzHugh-Nagumo
      reaction-diffusion model show both resonant and near-resonant patterns similar to
      the BZ chemical system.

PMID- 15244719
TI  - Crash test for the Copenhagen problem.
AB  - The Copenhagen problem is a simple model in celestial mechanics. It serves to
      investigate the behavior of a small body under the gravitational influence of two
      equally heavy primary bodies. We present a partition of orbits into classes of
      various kinds of regular motion, chaotic motion, escape and crash. Collisions of
      the small body onto one of the primaries turn out to be unexpectedly frequent,
      and their probability displays a scale-free dependence on the size of the
      primaries. The analysis reveals a high degree of complexity so that long term
      prediction may become a formidable task. Moreover, we link the results to chaotic
      scattering theory and the theory of leaking Hamiltonian systems.

PMID- 15244720
TI  - Liquid flow induced by ion evaporation in an electrified meniscus.
AB  - A simple model is proposed for the flow around the apex of a meniscus of a liquid
      undergoing ion evaporation in a vacuum under the action of a high electric field.
      The model includes a simplified description of the effect of the space charge
      surrounding the evaporating surface, and the idealizations that ion evaporation
      occurs at a constant surface field and that the electric field and viscous forces
      are negligible in the liquid. In agreement with known experimental and
      theoretical results for liquid metal ion sources, numerical solutions of the
      model problem show that the meniscus develops a protrusion and the current
      voltage characteristic is linear in a range of voltages above an extinction
      voltage at which evaporation switches off. An oscillatory regime and transient
      evolutions ending in surface pinch-off and the emission of a drop are described,
      and the stabilizing effect of the pressure variations due to the evaporation flux
      is discussed. Asymptotic estimates for large evaporation flow rates are worked
      out.

PMID- 15244721
TI  - Three-dimensional simulation of square jets in cross-flow.
AB  - Direct numerical simulations are performed to predict the three-dimensional
      unsteady flow interactions in the near-field of a square jet issuing normal to a
      cross-flow. The simulated flow features reveal the formation of an upstream
      horseshoe vortex system, which is the result of an interaction between the
      oncoming channel floor shear layer and the transverse jet; the growth of a
      sequence of Kelvin-Helmholtz instability-induced vortical rollers in the mixing
      layer between the jet and the cross-flow, which wrap around the front side of the
      jet; and the inception process of the counter-rotating vortex pair (CVP), which
      is initiated through the folding of the lateral jet shear layers. It has been
      observed that for a square jet in cross-flow, the developed Kelvin-Helmholtz
      instability induced shear layer rollers do not form closed circumferential vortex
      rings. Along the downstream side of the jet, the extended tails of such rollers
      gradually join the locally evolving CVP. The very inception of the CVP is,
      however, observed to take place within the cross-flow-induced skewed lateral jet
      shear layers, and such inception was seen to occur slightly below the jet
      orifice. The simulated results also reveal the growth of the upright wake
      vortices from the topological singular points that developed on the cross-flow
      floor boundary layer. The accumulated floor vortices are seen to spiral around
      the critical points and subsequently leave the channel floor uprightly. During
      upward motion these vortices eventually get entrained into the CVP core. It has
      been made clear topologically that the unstable local surface excitations are the
      seeds from which upright vortices grow. Interestingly, such findings remain quite
      consistent with the existing experimental predictions for a round jet.
      Simulations were performed for two moderate values of the Reynolds number 225 and
      300, based on the jet width and the average cross-flow inlet velocity, and for
      two different values of the jet to cross-stream velocity ratio, 2.5 and 3.5.

PMID- 15244722
TI  - Dynamics of laser-induced electroconvection pulses.
AB  - We first report that, for planar nematic 4-methoxy-benzilidene-4-butylaniline
      (MBBA), the electroconvection threshold voltage has a nonmonotonic temperature
      dependence, with a well-defined minimum, and a slope of about -0.12 V/degrees C
      near room temperature at 70 Hz. Motivated by this observation, we have designed
      an experiment in which a weak continuous-wave absorbed laser beam with a diameter
      comparable to the pattern wavelength generates a locally supercritical region, or
      pulse, in dye-doped MBBA. Working 10-20 % below the laser-free threshold voltage,
      we observe a steady-state pulse shaped as an ellipse with the semimajor axis
      oriented parallel to the nematic director, with a typical size of several
      wavelengths. The pulse is robust, persisting even when spatially extended rolls
      develop in the surrounding region, and displays rolls that counterpropagate along
      the director at frequencies of tenths of Hz, with the rolls on the left (right)
      side of the ellipse moving to the right (left). Systematic measurements of the
      sample-voltage dependence of the pulse amplitude, spatial extent, and frequency
      show a saturation or decrease when the control parameter (evaluated at the center
      of the pulse) approaches approximately 0.3. We propose that the model for these
      pulses should be based on the theory of control-parameter ramps, supplemented
      with new terms to account for the advection of heat away from the pulse when the
      surrounding state becomes linearly unstable. The advection creates a negative
      feedback between the pulse size and the efficiency of heat transport, which we
      argue is responsible for the attenuation of the pulse at larger control-parameter
      values.

PMID- 15244723
TI  - Experimental demonstration of thermoacoustic energy conversion in a resonator.
AB  - Using thermoacoustic energy conversions, both amplification and damping of
      acoustic intensity are demonstrated. A differentially heated regenerator is
      installed near the velocity node of the resonator and thereby a high specific
      acoustic impedance and a traveling wave phase are obtained. It is shown that the
      gain of acoustic intensity resulting from the traveling wave energy conversion
      reaches 1.7 in a positive temperature gradient and 0.3 in a negative gradient.
      When the regenerator is replaced with a stack, it is found that the gain reaches
      2.3, exceeding the temperature ratio (=1.9) of both ends of the stack. This is
      brought about by the addition of standing wave energy conversion. The present
      results would contribute to the development of new acoustic devices using
      thermoacoustic energy conversion.

PMID- 15244724
TI  - Chaotic flow and efficient mixing in a microchannel with a polymer solution.
AB  - Microscopic flows are almost universally linear, laminar, and stationary because
      the Reynolds number, Re, is usually very small. That impedes mixing in
      microfluidic devices, which sometimes limits their performance. Here, we show
      that truly chaotic flow can be generated in a smooth microchannel of a uniform
      width at arbitrarily low Re, if a small amount of flexible polymers is added to
      the working liquid. The chaotic flow regime is characterized by randomly
      fluctuating three-dimensional velocity field and significant growth of the flow
      resistance. Although the size of the polymer molecules extended in the flow may
      become comparable to the microchannel width, the flow behavior is fully
      compatible with that in a macroscopic channel in the regime of elastic
      turbulence. The chaotic flow leads to quite efficient mixing, which is almost
      diffusion independent. For macromolecules, mixing time in this microscopic flow
      can be three to four orders of magnitude shorter than due to molecular diffusion.

PMID- 15244725
TI  - Double Rosensweig instability in a ferrofluid sandwich structure.
AB  - We consider a horizontal ferrofluid layer sandwiched between two layers of
      immiscible nonmagnetic fluids. In a sufficiently strong vertical magnetic field
      the flat interfaces between magnetic and nonmagnetic fluids become unstable to
      the formation of peaks. We theoretically investigate the interplay between these
      two instabilities for different combinations of the parameters of the fluids and
      analyze the evolving interfacial patterns. We also estimate the critical magnetic
      field strength at which thin layers disintegrate into an ordered array of
      individual drops.

PMID- 15244726
TI  - Macroscopic permeability of three-dimensional fracture networks with power-law
      size distribution.
AB  - Fracture network permeability is investigated numerically by using a three
      dimensional model of plane polygons uniformly distributed in space with sizes
      following a power-law distribution. Each network is triangulated via an advancing
      front technique, and the flow equations are solved in order to obtain detailed
      pressure and velocity fields. The macroscopic permeability is determined on a
      scale which significantly exceeds the size of the largest fractures. The
      influence of the parameters of the fracture size distribution--the power-law
      exponent and the minimal fracture radius--on the macroscopic permeability is
      analyzed. Eventually, a general expression is proposed, which is the product of a
      dimensional measure of the network density, weighted by the individual fracture
      conductivities, and of a fairly universal function of a dimensionless network
      density, which accounts for the influences of the fracture shapes and of the
      parameters of their size distribution. Two analytical formulas are proposed which
      successfully fit the numerical data over a wide range of network densities.

PMID- 15244727
TI  - Band gaps in the propagation and scattering of surface water waves over
      cylindrical steps.
AB  - Here we investigate the propagation and scattering of surface water waves in the
      presence of arrays of bottom-mounted cylindrical steps. Both periodic and random
      arrangements of the steps are considered. The wave transmission through the
      arrays is computed using the multiple scattering method based upon a recently
      derived formulation. For the periodic case, the results are compared to the band
      structure calculation. We demonstrate that complete band gaps can be obtained in
      such a system. Furthermore, we show that the randomization of the location of the
      steps can significantly reduce the transmission of water waves. Comparison with
      other systems is also discussed.

PMID- 15244728
TI  - Nonlinear flows in nearly incompressible hydrodynamic fluids.
AB  - Nearly incompressible viscous hydrodynamic fluids are investigated using
      nonlinear fluid simulations. Nearly incompressible fluids possess acoustic modes
      through high frequency fluctuations associated with the subsonic fluid Mach
      number. These modes, in combination with the fluid modes, drive linearly unstable
      modes and nonlinearly excite flows. The nonlinear flows damp the long wavelengths
      in our simulations, and are dissipated resonantly when certain nonlinear
      conditions are satisfied. In agreement with our analytic analysis, the
      nonlinearly saturated flows in nearly incompressible fluids are generated through
      the action of the Reynolds stress forces.

PMID- 15244729
TI  - Sedimentation dynamics of spherical particles in confined geometries.
AB  - We study the steady-state dynamics of sedimenting non-Brownian particles in
      confined geometries with full hydrodynamic interactions at small but finite
      Reynolds numbers. We employ extensive computer simulations using a method where a
      continuum liquid phase is coupled through Stokesian friction to a discrete
      particle phase. In particular, we consider a sedimentation box which is otherwise
      periodic except that it is confined by two parallel walls parallel to gravity
      with a spacing Lx. By systematically varying Lx we explore the change in dynamics
      from a quasi-two-dimensional (2D) case to a three-dimensional case. We find that
      in such confined geometries there is a depletion of particle number density at
      the walls for small volume fractions, while for large volume fractions there is
      an excess number of particles at the walls. For the average sedimentation
      velocity, we find that the Richardson-Zaki law is well obeyed but the decrease of
      the velocity for dilute systems is slower for smaller values of Lx. We study the
      anisotropy of the velocity fluctuations and find that in the direction of gravity
      there is excellent agreement with the predicted scaling with respect to Lx. We
      also find that the behavior of the corresponding diffusion coefficients as a
      function of Lx is qualitatively different in the direction parallel to gravity
      and perpendicular to it. In the quasi-2D limit where particles block each other,
      the velocity fluctuations behave differently from the other confined systems.

PMID- 15244730
TI  - Hexagonal pattern instabilities in rotating Rayleigh-Benard convection of a non
      Boussinesq fluid: experimental results.
AB  - Motivated by the Kuppers-Lortz instability of roll patterns in the presence of
      rotation, we have investigated the effects of rotation on a hexagonal pattern in
      Rayleigh-Benard convection. While several theoretical models have been developed,
      experimental data cannot be found in the literature. In order to check the
      validity of the predictions and to study the effects of rotation on the behavior
      of the system, we present experimental results for a non-Boussinesq Rayleigh
      Benard convection with rotation about the vertical axis. Rotation introduces an
      additional control parameter, namely the dimensionless rotation rate Omega= 2 pi
      f d(2)/nu, where f is the rotation rate (in Hz), d is the thickness of the cell,
      and nu is the kinematic viscosity. We observe that the cell rotation induces a
      slow rotation of the pattern in the opposite direction (approximately Omega x 10(
      4) ) in the rotating frame. Moreover, it tends to destroy the convective pattern.
      No oscillation of the hexagonal pattern over the range of its existence (Omega<
      or =6) has been observed.

PMID- 15244731
TI  - Time-dependent gap Hele-Shaw cell with a ferrofluid: evidence for an interfacial
      singularity inhibition by a magnetic field.
AB  - We consider the flow of a ferrofluid droplet in a Hele-Shaw cell with a time
      dependent gap width. When the surface tension and applied magnetic field are
      zero, interfacial instabilities develop and the droplet breaks. We execute a mode
      coupling approach to the problem and focus on understanding how the development
      of singularities is affected by the action of an external field. Our analytical
      results indicate that the introduction of an azimuthal magnetic field profoundly
      modifies pattern formation, allowing the inhibition of interfacial singularities.
      We suggest the magnetic field can be used as a controllable parameter to
      discipline singular behavior.

PMID- 15244732
TI  - Cascade time scales for energy and helicity in homogeneous isotropic turbulence.
AB  - We extend the Kolmogorov phenomenology for the scaling of energy spectra in high
      Reynolds-number turbulence, to explicitly include the effect of helicity. There
      exists a time scale tau(H) for helicity transfer in homogeneous, isotropic
      turbulence with helicity. We arrive at this time scale using the phenomenological
      arguments used by Kraichnan to derive the time scale tau(E) for energy transfer
      [J. Fluid Mech. 47, 525 (1971)]]. We show that in general tau(H) may not be
      neglected compared to tau(E), even for rather low relative helicity. We then
      deduce an inertial range joint cascade of energy and helicity in which the
      dynamics are dominated by tau(E) in the low wave numbers with both energy and
      helicity spectra scaling as k(-5/3); and by tau(H) at larger wave numbers with
      spectra scaling as k(-4/3). We demonstrate how, within this phenomenology, the
      commonly observed "bottleneck" in the energy spectrum might be explained. We
      derive a wave number k(h) which is less than the Kolmogorov dissipation wave
      number, at which both energy and helicity cascades terminate due to dissipation
      effects. Data from direct numerical simulations are used to check our
      predictions.

PMID- 15244733
TI  - Swift-Hohenberg model for magnetoconvection.
AB  - A model system of partial differential equations in two dimensions is derived
      from the three-dimensional equations for thermal convection in a horizontal fluid
      layer in a vertical magnetic field. The model consists of an equation of Swift
      Hohenberg type for the amplitude of convection, coupled to an equation for a
      large-scale mode representing the local strength of the magnetic field. The model
      facilitates both analytical and numerical studies of magnetoconvection in large
      domains. In particular, we investigate the phenomenon of flux separation, where
      the domain divides into regions of strong convection with a weak magnetic field
      and regions of weak convection with a strong field. Analytical predictions of
      flux separation based on weakly nonlinear analysis are extended into the fully
      nonlinear regime through numerical simulations. The results of the model are
      compared with simulations of the full three-dimensional magnetoconvection
      problem.

PMID- 15244734
TI  - Sign-symmetry of temperature structure functions.
AB  - New scalar structure functions with different sign-symmetry properties are
      defined. These structure functions possess different scaling exponents even when
      their order is the same. Their scaling properties are investigated for second and
      third orders, using data from high-Reynolds-number atmospheric boundary layer. It
      is only when structure functions with disparate sign-symmetry properties are
      compared can the extended self-similarity detect two different scaling ranges
      that may exist, as in the example of convective turbulence.

PMID- 15244735
TI  - Intermittency exponent of the turbulent energy cascade.
AB  - We consider the turbulent energy dissipation from one-dimensional records in
      experiments using air and gaseous helium at cryogenic temperatures, and obtain
      the intermittency exponent via the two-point correlation function of the energy
      dissipation. The air data are obtained in a number of flows in a wind tunnel and
      the atmospheric boundary layer at a height of about 35 m above the ground. The
      helium data correspond to the centerline of a jet exhausting into a container.
      The air data on the intermittency exponent are consistent with each other and
      with a trend that increases with the Taylor microscale Reynolds number,
      R(lambda), of up to about 1000 and saturates thereafter. On the other hand, the
      helium data cluster around a constant value at nearly all R(lambda), this being
      about half of the asymptotic value for the air data. Some possible explanation is
      offered for this anomaly.

PMID- 15244736
TI  - Stable sonoluminescence within a water hammer tube.
AB  - The sonoluminescence (SL) from the collapse of a single gas bubble within a
      liquid can be produced repetitively using an acoustic resonator. An alternative
      technique using a water hammer tube, producing SL from bubbles of greater size,
      is described here. A sealed vertical tube partly filled with a liquid and a gas
      at low pressure is subjected to vertical vibrations. The oscillation of the
      pressure within the liquid column, due to inertial forces, excites cavitation
      bubbles to grow and collapse. Rotation is used to confine the bubbles to the axis
      of the tube. Bright SL emissions were observed in a number of liquids. Repetitive
      emission was produced from bubbles in condensed phosphoric acid. Bubbles of 0.4
      mm ambient radius (containing 2x 10(14) xenon atoms) were excited by vibration at
      35 Hz. Approximately 10(12) photons were emitted per collapse in the range 400
      700 nm (over four orders of magnitude greater than the brightest SL reported
      previously), corresponding to a 1% efficiency of the conversion of mechanical
      energy into light.

PMID- 15244737
TI  - Crossing the elliptic region in a hyperbolic system with change-of-type behavior
      arisingin flow between two parallel plates.
AB  - Change-of-type behavior from hyperbolic to elliptic is common to quasilinear
      hyperbolic systems. This issue is addressed here for the particular case of
      miscible flow of three fluids between two parallel plates. Change of type occurs
      at the leading edge of the displacement front and reflects the failing of the
      equilibrium assumption, necessary for the quasilinear hyperbolic formalism, at
      the front. To cross the elliptic region requires the solution of the full, higher
      dimensionality problem, obtained here using lattice gas simulations. For the
      specific example, it is found that the system self-selects a front structure
      independent of injection conditions.

PMID- 15244738
TI  - Spatially modulated thermal convection of viscoelastic fluids.
AB  - The thermal convection of modulated viscoelastic flow is examined in this study.
      The modulation is assumed to be weak enough for a regular perturbation solution
      to be implemented. In addition to being more accurate, the second-order
      perturbation results reveal new physical phenomena that could not be predicted by
      the first-order analysis. Inertia was found to enhance globally the discrepancies
      between the first- and the second-order perturbation solution. A comparison
      between the Newtonian and the non-Newtonian solution is carried out and the
      influences of inertia, modulation amplitude, and wave number are emphasized. The
      present results show that elasticity has a marked effect on fluid patterns,
      especially regarding the roll structure and symmetry. The influence of elasticity
      is greater for larger Rayleigh number and aspect ratio.

PMID- 15244739
TI  - Electrostatic modes in collisional complex plasmas under microgravity conditions.
AB  - A linear dispersion relation in a highly collisional complex plasma, including
      ion drift, was derived in the light of recent PKE-Nefedov wave experiment
      performed under microgravity conditions onboard the International Space Station.
      Two modifications of dust density waves with wave frequencies larger than the
      dust-neutral collision frequency were obtained. The relevance to the space
      observations was analyzed and a comparison of theory and observations was made
      for two different complex plasma domains formed by small and large
      microparticles. Good qualitative agreement is found between the measurements and
      the theoretical dispersion relations. This allows a determination of the basic
      complex plasma parameters.

PMID- 15244740
TI  - Description of strongly coupled Yukawa fluids using the variational modified
      hypernetted chain approach.
AB  - The variational modified hypernetted chain approach as proposed by J. Stat. Phys.
      42, 437 (1986)] is used to describe strongly coupled Yukawa fluids. The integral
      equations of interest can be solved using the spherical harmonic oscillator wave
      functions as a seed. Comparisons are done with simulation results for equation of
      state and transport coefficients over the entire fluid domain for a wide range of
      the system parameters.

PMID- 15244741
TI  - Kinetic theory of Jeans instability.
AB  - Kinetic treatment of the Jeans gravitational instability, with collisions taken
      into account, is presented. The initial-value problem for the distribution
      function which obeys the kinetic equation, with the collision integral conserving
      the number of particles, is solved. Dispersion relation is obtained and analyzed.
      New modes are found. Collisions are shown not to affect the Jeans instability
      criterion. Although the instability growth rate diminishes, the collisions they
      cannot quench the instability. However, the oscillation spectrum is modified
      significantly: even in the neighborhood of the threshold frequency omega=0
      (separating stable and unstable modes) the spectrum of oscillations can strongly
      depend on the collision frequency. Propagating (rather than aperiodic) modes are
      also found. These modes, however, are strongly damped.

PMID- 15244742
TI  - Preplasma conditions for operation of 10-Hz subjoule femtosecond-laser-pumped
      nickel-likex-ray lasers.
AB  - We present measurements of electron densities of plasmas with femtosecond (fs)
      temporal resolution. The plasmas are generated by laser pulses with different
      intensities at different time delays. Such plasmas are of great interest as
      preplasmas for transient, collisionally excited x-ray lasers. The laser pulses
      producing the plasmas are generated by stretching part of a 130-fs laser pulse of
      the ATLAS titanium-sapphire laser of our institute and focusing this radiation to
      a line on molybdenum and silver slab targets. The electron density is measured as
      a function of distance from the target by interferometry using a Wollaston prism.
      Using an ultrashort probe pulse allows one to obtain data extremely close, about
      10 microm, to the target surface. Experimental data are compared with simulations
      using the MULTI hydrocode. The results allow comparison of the ablation from a
      hard (Mo) and a soft (Ag) material, optimization of prepulse-main pulse delay
      times, and selection of the best pump geometry allowing for propagation of the
      pump and x-ray beams. These points are key elements for the development of a high
      repetition-rate soft-x-ray laser.

PMID- 15244743
TI  - Collisional-radiative study of lithium plasmas.
AB  - The sensitivity of lithium plasma models to the underlying atomic data is
      investigated. Collisional-radiative modeling is carried out with both the Los
      Alamos and ADAS suite of codes. The effects of plane-wave Born, distorted-wave,
      and nonperturbative R -matrix with pseudostates and time-dependent close-coupling
      electron impact atomic data on derived plasma quantities such as the ionization
      balance and radiated power are studied. Density and temperature regimes are
      identified where nonperturbative excitation and ionization rate coefficients must
      be used. The electron temperature and density ranges investigated were 0.2 eV< or
      = T(e) < or =90 eV and 10(10) cm(-3) < or = N(e) < or = 10(14) cm(-3).

PMID- 15244744
TI  - Propagation characteristics and guiding of a high-power microwave in plasma
      waveguide.
AB  - The propagation characteristics of a high-power microwave [electromagnetic (em)
      wave] in a plasma waveguide are reported. The plasma waveguide is formed by
      expanding plasmas via the ponderomotive force of the high-power microwave and the
      microwave pulse remains trapped within the plasma waveguide and is guided in it.
      With the increase of the incident microwave power, the width of the plasma
      waveguide increases and the half width of the radial electric field distribution
      decreases. This shows that the em wave modifies the refractive index of the
      plasma waveguide area. For a plasma waveguide with narrower width, the microwave
      propagates along the plasma waveguide at the fundamental TE mode, while as the
      waveguide width increases the higher mode component starts appearing. Analytical
      treatment to the propagation of the electromagnetic wave in a dielectric
      waveguide having a step-index profile and the numerical calculations for the
      radial distribution of the electric field show fairly good agreement with the
      results observed in the present experiments.

PMID- 15244745
TI  - Inverse bremsstrahlung and temperature relaxation in moderately coupled two
      temperature plasmas.
AB  - The balance equation for the energy in moderately coupled two-temperature
      plasmas, in the presence of an external radiation field, is derived and analyzed.
      The analysis is based on the Singwi-Tosi-Land-Sjolander closure assumption. The
      different terms in the derived equation are identified as the rate of collisional
      energy absorption from the external field (inverse bremsstrahlung), and the rate
      of energy transfer between the electrons and the ions in the presence of the
      radiation field (relaxation). It is shown how these terms, which have a
      structurally similar appearance, reduce to known expressions for relaxation and
      inverse bremsstrahlung in the appropriate limits. It is found that, relative to
      the known expressions, electron-ion correlation tends to enhance the rates of
      re1axation and of the inverse bremsstrahlung process.

PMID- 15244746
TI  - Optical-field-ionization effects on the propagation of an ultraintense laser
      pulse in high- Z gas jets.
AB  - Interaction of an ultraintense, a(0) >>1, laser pulse with an underdense Ar
      plasma is analyzed via a two-dimensional particle-in-cell simulation which self
      consistently includes optical-field ionization. In spite of rapid growth of ion
      charge Z and, hence, electron density at the laser front, relativistic self
      focusing is shown to persist owing to a reduction of the expected plasma
      defocusing resulting from the weak radial dependence of the ion charge on laser
      intensity (even for Z/gamma>1 where gamma is the electron relativistic factor).

PMID- 15244747
TI  - Resonance acceleration of electrons in combined strong magnetic fields and
      intense laser fields.
AB  - The acceleration mechanism of electrons in combined strong axial magnetic fields
      and circularly polarized laser pulse fields is investigated by solving the
      dynamical equations for relativistic electrons both numerically and analytically.
      We find that the electron acceleration depends not only on the laser intensity,
      but also on the ratio between electron Larmor frequency and laser frequency. As
      the ratio approaches unity, a clear resonance peak is observed, corresponding to
      the laser-magnetic resonance acceleration. Away from the resonance regime, the
      strong magnetic fields still affect the electron acceleration dramatically. We
      derive an approximate analytical solution of the relativistic electron energy in
      adiabatic limit, which provides a full understanding of this phenomenon.
      Application of our theory to fast ignition of inertial confinement fusion is
      discussed.

PMID- 15244748
TI  - Laser self-focusing in the presence of quasistatic axial direct current.
AB  - We try to understand the presence of a quasistatic magnetic field on the basis of
      the stability of the laser-plasma system. A general theoretical model of laser
      self-focusing in the absence of a quasistatic magnetic field (QMF) is extended to
      discuss self-focusing in the presence of a QMF. Various transverse intensity
      profiles under different axial collective electronic speeds V(z) are calculated.
      Numerical results indicate that for suitable laser power and plasma density, the
      increment in V(z) can lead to a further separation between the photon fluid and
      the electron fluid and hence a decrement in the energy of the laser-plasma
      system. This causes it to be possible for the system state without a QMF, or V(z)
      =0 state, to be not stable relative to some V(z) not equal 0 states.

PMID- 15244749
TI  - Dusty plasmas in a constant electric field: role of the electron drag force.
AB  - We investigate the forces experienced by a microparticle immersed in a weakly
      ionized plasma with constant electric field. These are electric force and the
      forces associated with the momentum transfer from electrons and ions drifting in
      the field (electron and ion drag forces). It is shown that the effect of the
      electron drag, which is often neglected, can be substantial in a certain
      parameter range. Numerical calculation of the forces for a reasonable set of
      plasma parameters is performed to illustrate the importance of this effect.

PMID- 15244750
TI  - Internal versus external conductivity of a dense plasma: many-particle theory and
      simulations.
AB  - In the long-wavelength limit k=0, the response function has been investigated
      with respect to the external and internal fields which is expressed by the
      external and internal conductivity, respectively. Molecular dynamics simulations
      are performed to obtain the current-current correlation function and the
      dynamical collision frequency which are compared with analytical expressions.
      Special attention is given to the dynamical collision frequency and the
      description of plasma oscillations in the case of k=0. The relation between the
      external and internal conductivity and the current-current correlation function
      is analyzed.

PMID- 15244751
TI  - Pump side scattering in ultrapowerful backward Raman amplifiers.
AB  - Extremely large laser power might be obtained by compressing laser pulses through
      backward Raman amplification (BRA) in plasmas. Premature Raman backscattering of
      a laser pump by plasma noise might be suppressed by an appropriate detuning of
      the Raman resonance, even as the desired amplification of the seed persists with
      a high efficiency. In this paper we analyze side scattering of laser pumps by
      plasma noise in backward Raman amplifiers. Though its growth rate is smaller than
      that of backscattering, the side scattering can nevertheless be dangerous,
      because of a longer path of side-scattered pulses in plasmas and because of an
      angular dependence of the Raman resonance detuning. We show that side scattering
      of laser pumps by plasma noise in BRA might be suppressed to a tolerable level at
      all angles by an appropriate combination of two detuning mechanisms associated
      with plasma density gradient and pump chirp.

PMID- 15244752
TI  - K(alpha) fluorescence measurement of relativistic electron transport in the
      context of fast ignition.
AB  - Electron transport within solid targets, irradiated by a high-intensity short
      pulse laser, has been measured by imaging K(alpha) radiation from high- Z layers
      (Cu, Ti) buried in low- Z (CH, Al) foils. Although the laser spot is
      approximately 10 microm [full width at half maximum (FWHM)], the electron beam
      spreads to > or =70 microm FWHM within <20 microm of penetration into an Al
      target then, at depths >100 microm, diverges with a 40 degree spreading angle.
      Monte Carlo and analytic models are compared to our data. We find that a Monte
      Carlo model with a heuristic model for the electron injection gives a reasonable
      fit with our data.

PMID- 15244753
TI  - Ultrashort laser pulses and electromagnetic pulse generation in air and on
      dielectric surfaces.
AB  - Intense, ultrashort laser pulses propagating in the atmosphere have been observed
      to emit sub-THz electromagnetic pulses (EMPS). The purpose of this paper is to
      analyze EMP generation from the interaction of ultrashort laser pulses with air
      and with dielectric surfaces and to determine the efficiency of conversion of
      laser energy to EMP energy. In our self-consistent model the laser pulse
      partially ionizes the medium, forms a plasma filament, and through the
      ponderomotive forces associated with the laser pulse, drives plasma currents
      which are the source of the EMP. The propagating laser pulse evolves under the
      influence of diffraction, Kerr focusing, plasma defocusing, and energy depletion
      due to electron collisions and ionization. Collective effects and recombination
      processes are also included in the model. The duration of the EMP in air, at a
      fixed point, is found to be a few hundred femtoseconds, i.e., on the order of the
      laser pulse duration plus the electron collision time. For steady state laser
      pulse propagation the flux of EMP energy is nonradiative and axially directed.
      Radiative EMP energy is present only for nonsteady state or transient laser pulse
      propagation. The analysis also considers the generation of EMP on the surface of
      a dielectric on which an ultrashort laser pulse is incident. For typical laser
      parameters, the power and energy conversion efficiency from laser radiation to
      EMP radiation in both air and from dielectric surfaces is found to be extremely
      small, < 10(-8). Results of full-scale, self-consistent, numerical simulations of
      atmospheric and dielectric surface EMP generation are presented. A recent
      experiment on atmospheric EMP generation is also simulated.

PMID- 15244754
TI  - Nonlocal effects in high-energy charged-particle beams.
AB  - Within the framework of the thermal wave model, an investigation is made of the
      longitudinal dynamics of high-energy charged-particle beams. The model includes
      the nonlinear self-consistent interaction between the beam and its surroundings
      in terms of a coupling impedance, and when resistive as well as reactive parts
      are included, the evolution equation becomes a generalized nonlinear Schrodinger
      equation including a nonlocal nonlinear term. The consequences of the resistive
      part on the propagation of particle bunches are examined using analytical as well
      as numerical methods.

PMID- 15244755
TI  - Mechanisms for phase distortion in a traveling wave tube.
AB  - We present a view of the physics of phase distortion in a traveling wave tube
      (TWT) based on unique insights afforded by the MUSE models of a TWT [IEEE Trans.
      Plasma Sci. 30, 1063 (2002)]]. The conclusion, supported by analytic theory and
      simulations, is that prior to gain compression phase distortion is due to
      harmonic frequencies in the electron beam and the resulting "intermodulation"
      frequency at the fundamental, and not the often cited "slowing down of electrons
      in the electron beam." We draw these conclusions based on MUSE simulations that
      allow explicit control of electron beam frequency content, an analytic solution
      to the S-MUSE model [IEEE Trans. Plasma Sci. 30, 1063 (2002)]] that reveals that
      phase distortion is due to the fact that the fundamental frequency is an
      intermodulation product of itself, and large signal LATTE [IEEE Trans. Plasma
      Sci. 30, 1063 (2002)]] simulations that are modified to remove the effect of the
      slowing down of electrons in the electron beam. As applications of the theory we
      compare S-MUSE simulations to an amplitude phase model using the analytic phase
      transfer curve, we study dependence of phase distortion on circuit dispersion and
      electron beam parameters at the second harmonic with large signal LATTE
      simulations for narrow and wide band TWT designs, and we consider the phase
      distortion theory in the context of TWT linearization.

PMID- 15244756
TI  - Model for nonlinear behavior in the self-amplified spontaneous-emission free
      electron laser.
AB  - We introduce a simplified model for the saturation of a self-amplified
      spontaneous-emission free-electron laser. Within this model, we determine the
      effect of nonlinearity upon the statistical properties of the output radiation.
      Comparing our results with the computer simulations of Saldin, Schneidmiller, and
      Yurkov [The Physics of Free Electron Lasers (Springer-Verlag, Berlin, 2000)], we
      find that the model provides a good description of the average intensity, field
      correlation function, and coherence time, but underestimates the intensity
      fluctuation. Asymmetric spectral broadening phenomena are not included in the
      model.

PMID- 15244757
TI  - One-dimensional ordering of ultra-low-density ion beams in a storage ring.
AB  - The two-particle model, first introduced by Hasse, is employed to predict the
      beam temperature at which a one-dimensional ordered state of ions will be
      established in a cooler storage ring. The proposed state does not have the ions
      (in the beam frame) at rest, but simply has them not passing each other; i.e.,
      remaining in the same (ordered) sequence. The model is applicable to an ultra-low
      density beam where collective Coulomb interactions are negligible. It is pointed
      out that the nature of the anomalous beam behavior observed in electron-cooling
      experiments at GSI (Darmstadt) and MSL (Stockholm) is approximately free from
      such parameters as the lattice design, ion species, beam density, and energy. On
      the basis of the model, which is put in Hamiltonian form, scaled, and numerically
      studied, a universal criterion of one-dimensional beam ordering at low line
      density is derived. Analytic work is employed to explain the numerical results
      and derives an approximate criterion.

PMID- 15244758
TI  - Trapping and steering on lattice strings: Virtual slow waves and directional and
      nonpropagating excitations.
AB  - Using a lattice string model, a number of peculiar excitation situations related
      to nonpropagating excitations and nonradiating sources are demonstrated. External
      fields can be used to trap excitations locally but also lead to the ability to
      steer such excitations dynamically as long as the steering is slower than the
      field's wave propagation. I present explicit constructions of a number of
      examples, including temporally limited nonpropagating excitations, directional
      excitation and virtually slowed propagation. Using these dynamical lattice
      constructions I demonstrate that neither persistent temporal oscillation nor
      static localization are necessary for nonpropagating excitations to occur.

PMID- 15244759
TI  - Exact analytic expressions for electromagnetic propagation and optical nonlinear
      generation in finite one-dimensional periodic multilayers.
AB  - The translation matrix formalism has been used to find an exact analytic solution
      for linear light propagation in a finite one-dimensional periodic stratified
      structure. This modal approach allows us to derive a closed formula for the
      electric field in every point of the structure, by simply imposing a convenient
      form for the boundary conditions. We show how to apply this result to second
      harmonic generation in the undepleted pump regime.

PMID- 15244760
TI  - Description of readout processes during strong beam coupling.
AB  - We show, using the symmetry properties of the coupled-wave equations for the
      transmission and reflection geometries, that any readout characteristic of
      dynamic spatially nonuniform index gratings in photorefractive crystals can be
      explicitly expressed through the characteristics of the recording light beams.
      This approach is applied to describe the impact of beam coupling on the
      diffraction efficiency of dynamic gratings and on the output intensities of the
      light beams at instantaneous input phase changes (light grating translation).
      Further implications of this general approach are discussed.

PMID- 15244761
TI  - Inverse scattering transform for the derivative nonlinear Schrodinger equation
      with nonvanishing boundary conditions.
AB  - An inverse scattering transform for the derivative nonlinear Schrodinger equation
      with nonvanishing boundary conditions is derived by introducing an affine
      parameter to avoid constructing Riemann sheets. A one-soliton solution simpler
      than that in the literature is obtained, which is a breather and degenerates to a
      bright or dark soliton as the discrete eigenvalue becomes purely imaginary. The
      solution is mapped to that of the modified nonlinear Schrodinger equation by a
      gaugelike transformation, predicting some sub-picosecond solitons in optical
      fibers.

PMID- 15244762
TI  - Energy spectrum evolution of a diffuse field in an elastic body caused by weak
      nonlinearity.
AB  - We study the evolution of diffuse elastodynamic spectral energy density under the
      influence of weak nonlinearity. It is shown that the rate of change of this
      quantity is given by a convolution of the linear energy at two frequencies.
      Quantitative estimates are given for sample aluminum and fused silica blocks of
      experimental interest.

PMID- 15244763
TI  - Localized and stationary light wave modes in dispersive media.
AB  - In recent experiments, localized and stationary optical wave packets have been
      generated in second-order nonlinear processes with femtosecond pulses, whose
      asymptotic features relate to those of nondiffracting and nondispersing
      polychromatic Bessel beams in linear dispersive media. We investigate the nature
      of these linear waves and show that they can be identified with the X-shaped (O
      shaped) modes of the hyperbolic (elliptic) wave equation in media with normal
      (anomalous) dispersion. Depending on the relative strengths of mode phase
      mismatch, group velocity mismatch with respect to a plane pulse, and the defeated
      group velocity dispersion, these modes can adopt the form of pulsed Bessel beams,
      focus wave modes, and X waves (O waves), respectively.

PMID- 15244764
TI  - Properties of one-dimensional photonic crystals containing single-negative
      materials.
AB  - The transmission properties of a one-dimensional photonic crystal containing two
      kinds of single-negative (permittivity- or permeability-negative) media are
      studied theoretically. We show that this structure can possess a type of photonic
      gap with zero effective phase (phi(eff) ). The zero-phi(eff) gap distinguishes
      itself from a Bragg gap in that it is invariant with a change of scale length and
      is insensitive to thickness fluctuation. In contrast to a photonic gap
      corresponding to zero averaged refractive index, the zero-phi(eff) gap can be
      made very wide by varying the ratio of the thicknesses of two media. An
      equivalent transmission-line model is utilized to explain the properties. A
      photonic quantum-well structure based on zero-phi(eff) gaps is proposed as a
      multiple channeled filter that is compact and robust against disorder.

PMID- 15244765
TI  - Noisy spectra, long correlations, and intermittency in wave turbulence.
AB  - We study the k-space fluctuations of the wave action about its mean spectrum in
      the turbulence of dispersive waves. We use a minimal model based on the random
      phase approximation (RPA) and derive evolution equations for the arbitrary-order
      one-point moments of the wave intensity in the wave-number space. The first
      equation in this series is the familiar kinetic equation for the mean wave-action
      spectrum, whereas the second and higher equations describe the fluctuations about
      this mean spectrum. The fluctuations exhibit a nontrivial dynamics if some long
      coordinate-space correlations are present in the system, as it is the case in
      typical numerical and laboratory experiments. Without such long-range
      correlations, the fluctuations are trivially fixed at their Gaussian values and
      cannot evolve even if the wave field itself is non-Gaussian in the coordinate
      space. Unlike the previous approaches based on smooth initial k-space cumulants,
      the RPA model works even for extreme cases where the k-space fluctuations are
      absent or very large and intermittent. We show that any initial non-Gaussianity
      at small amplitudes propagates without change toward the high amplitudes at each
      fixed wave number. At each fixed amplitude, however, the probability distribution
      function becomes Gaussian at large time.

PMID- 15244766
TI  - Splitting and tuning characteristics of the point defect modes in two-dimensional
      phononic crystals.
AB  - Point defect modes of acoustic wave in two-dimensional square arrays of square
      water rods in a mercury host were studied. The defects are created by three kinds
      of geometry, namely, square defect, circular defect, and rectangular defect,
      respectively. The results show that for both square defect and circular defect,
      the defect modes are only related to the defect filling fraction F(d), but not
      with the geometry of defects (square or circular), as well as the orientations of
      the square defect. For the rectangular defect, the defect modes could be tuned by
      changing the ratio of edge width of the defect, moreover, the double degenerate
      one will split into two nondegenerate modes when the ratio of edge widths Lx /
      L(y) >9.0. Meanwhile the corresponding pressure distributions also will be
      changed.

PMID- 15244767
TI  - Symmetric and asymmetric solitons in linearly coupled Bragg gratings.
AB  - We demonstrate that a symmetric system of two linearly coupled waveguides, with
      Kerr nonlinearity and resonant grating in both of them, gives rise to a family of
      symmetric and antisymmetric solitons in an exact analytical form, a part of which
      exists outside of the bandgap in the system's spectrum, i.e., they may be
      regarded as embedded solitons (ES's, i.e., the ones partly overlapping with the
      continuous spectrum). Parameters of the family are the soliton's amplitude and
      velocity. Asymmetric ES's, unlike the regular (nonembedded) gap solitons (GS's),
      do not exist in the system. Moreover, ES's exist even in the case when the
      system's spectrum contains no bandgap. The main issue is the stability of the
      solitons. We demonstrate that some symmetric ES's are stable, while all the
      antisymmetric solitons are unstable; an explanation is given to the latter
      property, based on the consideration of the system's Hamiltonian. We produce a
      full stability diagram, which comprises both embedded and regular solitons,
      quiescent and moving. A stability region for ES's is found around the point where
      the constant of the linear coupling between the two cores is equal to the Bragg
      reflectivity coefficient accounting for the linear conversion between the right-
      and left-traveling waves in each core, i.e., the ES's are the "most endemic"
      solitary solitons in this system. The stability region quickly shrinks with the
      increase of the soliton's velocity c, and completely disappears when c exceeds
      half the maximum velocity. Collisions between stable moving solitons of various
      types are also considered, with a conclusion that the collisions are always
      quasielastic.

PMID- 15244768
TI  - Soliton solution of continuum magnetization equation in a conducting ferromagnet
      with a spin-polarized current.
AB  - Exact soliton solutions of a modified Landau-Lifshitz equation for the
      magnetization of conducting ferromagnet in the presence of a spin-polarized
      current are obtained by means of inverse scattering transformation. From the
      analytical solution the effects of spin current on the frequency, wave number,
      and dispersion law of spin wave are investigated. The one-soliton solution
      indicates obviously current-driven precession and periodic shape variation as
      well. The inelastic collision of solitons, by which we mean the shape change
      before and after collision, appears due to the spin current. We, moreover, show
      that complete inelastic collisions can be achieved by adjusting spectrum and
      current parameters. This may lead to an potential technique for shape control of
      spin wave.

PMID- 15244769
TI  - Guiding optical flows by photonic crystal slabs made of dielectric cylinders.
AB  - We investigate the electromagnetic propagation in two-dimensional photonic
      crystals, formed by parallel dielectric cylinders embedded in a uniform medium.
      The frequency band structure is computed using the standard plane-wave expansion
      method, while the propagation and scattering of the electromagnetic waves are
      calculated by the multiple scattering theory. It is shown that within partial
      band gaps, the waves tend to bend away from the forbidden directions. Such a
      property may render novel applications in manipulating optical flows. In
      addition, the relevance with the imaging by flat photonic crystal slabs will also
      be discussed.

PMID- 15244770
TI  - Band structure and omnidirectional photonic band gap in lamellar structures with
      left-handed materials.
AB  - We theoretically investigate the photonic band structure of one-dimensional
      superlattices composed of alternating layers of right-handed and left-handed
      materials (RHM and LHM). The dispersion curves are mainly studied by assuming
      that the dielectric permittivity and magnetic permeability are constant in each
      layer. It is shown that such structures can exhibit new types of electromagnetic
      modes and dispersion curves that do not exist in usual superlattices composed
      only of RHM. In particular, we emphasize the possibility of bands that originate
      from the interface modes localized at the boundary between a LHM and RHM or from
      confined modes in one type of layers. These waves are evanescent in both or in
      one constituent of the superlattice. One of the pass bands may lie below the
      light lines of the constituting material and go down to the static limit of a
      vanishing frequency omega, even at a value of the wave vector k(//) (parallel to
      the layers) that is different from zero. For a given value of the wave vector
      k(//), the dispersion curves omega versus k(z) (where k(z) is the Bloch wave
      vector of the periodic system along the axis of the superlattice) may exist only
      in a limited part of the superlattice Brillouin zone and exhibit a zigzag
      behavior instead of a monotonic behavior as in usual superlattices. With an
      appropriate choice of the parameters, we show that it is possible to realize an
      absolute (or omnidirectional) band gap for either transverse electric (TE) or
      transverse magnetic (TM) polarization of the electromagnetic waves. A combination
      of two multilayer structures composed of RHM and LHM is proposed to realize, in a
      certain range of frequency, an omnidirectional reflector of light for both
      polarizations.

PMID- 15244771
TI  - Stable vortex solitons supported by competing quadratic and cubic nonlinearities.
AB  - We address the stability problem for vortex solitons in two-dimensional media
      combining quadratic and self-defocusing cubic [chi(2):chi(3)- ] nonlinearities.
      We consider the propagation of spatial beams with intrinsic vorticity S in such
      bulk optical media. It was earlier found that the S=1 and S=2 solitons can be
      stable, provided that their power (i.e., transverse size) is large enough, and it
      was conjectured that all the higher-order vortices with S> or =3 are always
      unstable. On the other hand, it was recently shown that vortex solitons with S>2
      and very large transverse size may be stable in media combining cubic self
      focusing and quintic self-defocusing nonlinearities. Here, we demonstrate that
      the same is true in the chi(2):chi(3)- model, the vortices with S=3 and S=4 being
      stable in regions occupying, respectively, approximately 3% and 1.5% of their
      existence domain. The vortex solitons with S>4 are also stable in tiny regions.
      The results are obtained through computation of stability eigenvalues, and are
      then checked in direct simulations, with a conclusion that the stable vortices
      are truly robust ones, easily self-trapping from initial beams with embedded
      vorticity. The dependence of the stability region on the chi(2) phase-mismatch
      parameter is specially investigated. We thus conclude that the stability of
      higher-order two-dimensional vortex solitons in narrow regions is a generic
      feature of optical media featuring the competition between self-focusing and self
      defocusing nonlinearities. A qualitative analytical explanation to this feature
      is proposed.

PMID- 15244772
TI  - Propagation inhibition and localization of electromagnetic waves in two
      dimensional random dielectric systems.
AB  - We rigorously calculate the propagation and scattering of electromagnetic waves
      by rectangular and random arrays of dielectric cylinders in a uniform medium. For
      regular arrays, the band structures are computed and complete bandgaps are
      discovered. For random arrays, the phenomenon of wave transmission and scattering
      is investigated and compared in two scenarios: (1) Wave propagating through the
      array of cylinders; this is the scenario which has been commonly considered in
      the literature, and (2) wave transmitted from a source located inside the
      ensemble. We show that within complete band gaps, results from the two scenarios
      are similar. Outside the gaps, however, there could be a distinct difference,
      that is, wave transmission can be inhibited by disorders in the first scenario,
      but such an inhibition may not prevail in the second scenario.

PMID- 15244773
TI  - Quantum effects in the evolution of vortices in the electromagnetic field.
AB  - We analyze the influence of electron-positron pairs creation on the motion of
      vortex lines in electromagnetic field. In our approach the electric and magnetic
      fields satisfy nonlinear equations derived from the Euler-Heisenberg effective
      Lagrangian. We show that these nonlinearities may change the evolution of
      vortices.

PMID- 15244774
TI  - Lateral shift of the transmitted light beam through a left-handed slab.
AB  - It is reported that when a light beam travels through a slab of left-handed
      medium in the air, the lateral shift of the transmitted beam can be negative as
      well as positive. The necessary condition for the lateral shift to be positive is
      given. The validity of the stationary-phase approach is demonstrated by numerical
      simulations for a Gaussian-shaped beam. A restriction to the slab's thickness is
      provided that is necessary for the beam to retain its profile in the traveling.
      It is shown that the lateral shift of the reflected beam is equal to that of the
      transmitted beam in the symmetric configuration.

PMID- 15244775
TI  - One-dimensional bright discrete solitons in media with saturable nonlinearity.
AB  - A problem of pulse propagation in a homogeneous nonlinear waveguide array with
      saturable nonlinearity is studied. The corresponding model equation is the
      discretized Vinetskii-Kukhtarev equation with neglected influence of diffusion of
      charge carriers. For periodic boundary conditions, exact homogeneous and
      oscillating stationary solutions are found. A wide instability region of the
      homogeneous, array-independent solution is identified. An approximate analytical
      solution for the bright one-dimensional discrete soliton where the energy is
      concentrated mainly in a few waveguides is obtained. The soliton stability is
      investigated both analytically and numerically and a cascade nature of the
      saturation mechanism is revealed.

PMID- 15244777
TI  - Generalized 1/k-ensemble algorithm.
AB  - We generalize the 1/k-ensemble algorithm so that it can be used for both discrete
      and continuous systems, and show that the generalization is correct numerically
      and mathematically. We also compare the efficiencies of the generalized 1/k
      ensemble algorithm and the generalized Wang-Landau algorithm through a neural
      network example. The numerical results favor to the generalized 1/k-ensemble
      algorithm.

PMID- 15244776
TI  - Diffraction in crystalline colloidal-array photonic crystals.
AB  - We characterized the diffraction and crystal structure of a crystalline colloidal
      array (CCA) photonic crystal composed of 270 nm diameter polystyrene spheres
      which have a nearest neighbor spacing of approximately 540 nm. This CCA diffracts
      light in first order at approximately 1200 nm and shows strong diffraction in the
      visible spectral region from higher order planes. We quantitatively examined the
      relative diffraction intensities of the putative fcc (111), (200), (220), and
      (311) planes. Comparing these intensities to those calculated theoretically we
      find that the crystal structure is fcc with significant stacking faults.
      Essentially, no light transmits at the Bragg angle for the fcc (111) planes even
      through thin approximately 40 microm thick CCA. However, much of this light is
      diffusely scattered about the Bragg angle due to crystal imperfections.
      Significant transmission occurs from thin samples oriented at the Bragg condition
      for the fcc (200), (220), and (311) planes. We also observe moderately intense
      two-dimensional diffraction from the first few layers at the crystal surfaces. We
      also examined the sample thickness dependence of diffraction from CCA photonic
      crystals prepared from approximately 120 nm polystyrene spheres whose fcc (111)
      planes diffract in the visible spectral region. These experimental observations,
      aided by calculations based upon a simple but flexible model of light scattering
      from an arbitrary collection of colloidal spheres, make clear that fabrication of
      three-dimensional photonic band gap crystals will be challenged by crystal
      imperfections.

PMID- 15244778
TI  - Absorbing boundaries in time-dependent problems with discretized energy continua.
AB  - We develop a general method for removing artifacts associated with the numerical
      solution of time-dependent Schrodinger equation (TDSE) involving a (multiple)
      energy continuum discretization. This method is the equivalent to absorbing
      boundaries in the case where the space is discretized. By removing the reflected
      part of the wave function (on the artificial boundaries of the system), one is
      able to reduce the computational cost of the calculations, with a benefit scaling
      as the power of the continuum multiplicity. As a demonstration, we apply our
      method to the TDSE of a hydrogen atom subjected to a laser pulse, the spontaneous
      emission of a two-level atom in free space, and the interaction of two photons
      with a two-level atom and a defect mode at the edge of a photonic band gap.

PMID- 15244779
TI  - Extremal optimization at the phase transition of the three-coloring problem.
AB  - We investigate the phase transition in vertex coloring on random graphs, using
      the extremal optimization heuristic. Three-coloring is among the hardest
      combinatorial optimization problems and is equivalent to a 3-state anti
      ferromagnetic Potts model. Like many other such optimization problems, it has
      been shown to exhibit a phase transition in its ground state behavior under
      variation of a system parameter: the graph's mean vertex degree. This phase
      transition is often associated with the instances of highest complexity. We use
      extremal optimization to measure the ground state cost and the "backbone," an
      order parameter related to ground state overlap, averaged over a large number of
      instances near the transition for random graphs of size n up to 512. For these
      graphs, benchmarks show that extremal optimization reaches ground states and
      explores a sufficient number of them to give the correct backbone value after
      about O (n(3.5)) update steps. Finite size scaling yields a critical mean degree
      value alpha(c) =4.703 (28). Furthermore, the exploration of the degenerate ground
      states indicates that the backbone order parameter, measuring the constrainedness
      of the problem, exhibits a first-order phase transition.

PMID- 15244780
TI  - Nonlinear stochastic resonance with subthreshold rectangular pulses.
AB  - We analyze the phenomenon of nonlinear stochastic resonance (SR) in noisy
      bistable systems driven by pulsed time periodic forces. The driving force
      contains, within each period, two pulses of equal constant amplitude and duration
      but opposite signs. Each pulse starts every half period and its duration is
      varied. For subthreshold amplitudes, we study the dependence of the output signal
      to-noise ratio and the SR gain on the noise strength and the relative duration of
      the pulses. We find that the SR gains can reach values larger than unity, with
      maximum values showing a nonmonotonic dependence on the duration of the pulses.

PMID- 15244781
TI  - Scale-free networks with tunable degree-distribution exponents.
AB  - We propose and study a model of scale-free growing networks that gives a degree
      distribution dominated by a power-law behavior with a model-dependent, hence
      tunable, exponent. The model represents a hybrid of the growing networks based on
      popularity-driven and fitness-driven preferential attachments. As the network
      grows, a newly added node establishes m new links to existing nodes with a
      probability p based on popularity of the existing nodes and a probability 1-p
      based on fitness of the existing nodes. An explicit form of the degree
      distribution P(p,k) is derived within a mean field approach. For reasonably large
      k, P(p,k) approximately k(-gamma(p)) F(k,p), where the function F is dominated by
      the behavior of 1/ln (k/m) for small values of p and becomes k independent as p-
      >1, and gamma(p) is a model-dependent exponent. The degree distribution and the
      exponent gamma(p) are found to be in good agreement with results obtained by
      extensive numerical simulations.

PMID- 15244782
TI  - Error-correcting codes on scale-free networks.
AB  - We investigate the potential of scale-free networks as error-correcting codes. We
      find that irregular low-density parity-check codes with the highest performance
      known to date have degree distributions well fitted by a power-law function p (k)
      approximately k(-gamma) with gamma close to 2, which suggests that codes built on
      scale-free networks with appropriate power exponents can be good error-correcting
      codes, with a performance possibly approaching the Shannon limit. We demonstrate
      for an erasure channel that codes with a power-law degree distribution of the
      form p (k) = C (k+alpha)(-gamma), with k> or =2 and suitable selection of the
      parameters alpha and gamma, indeed have very good error-correction capabilities.

PMID- 15244783
TI  - Particle-cluster aggregation on a small-world network.
AB  - To describe the aggregation behaviors on substrates with long-range jump paths, a
      model of particle-cluster aggregation on a two-dimensional small-world network is
      presented. This model is characterized by two parameters: the clustering exponent
      alpha and the long-range connection rate phi. The results show that there exists
      an asymptotic fractal dimension D(max)(f) that depends upon alpha. With decrement
      of alpha, D(max)(f) varies from 1.7 to 2.0, which corresponds to a crossover from
      diffusion-limited-aggregation-like to dense growth. The change of the aggregation
      pattern results from the long-range connection in the network, which reduces the
      effect of screening during the aggregation. When the system size is not large
      enough, the effective fractal dimension D(f) depends upon phi because of the
      finite-size effect. With primitive analysis, we obtain the expression of the
      effective fractal dimension D(f) with the network parameters alpha and phi.

PMID- 15244784
TI  - Factors that predict better synchronizability on complex networks.
AB  - While shorter characteristic path length has in general been believed to enhance
      synchronizability of a coupled oscillator system on a complex network, the
      suppressing tendency of the heterogeneity of the degree distribution, even for
      shorter characteristic path length, has also been reported. To see this, we
      investigate the effects of various factors such as the degree, characteristic
      path length, heterogeneity, and betweenness centrality on synchronization, and
      find a consistent trend between the synchronization and the betweenness
      centrality. The betweenness centrality is thus proposed as a good indicator for
      synchronizability.

PMID- 15244785
TI  - Evolutionary dynamics and the phase structure of the minority game.
AB  - We show that a simple evolutionary scheme, when applied to the minority game
      (MG), changes the phase structure of the game. In this scheme each agent evolves
      individually whenever his wealth reaches the specified bankruptcy level, in
      contrast to the evolutionary schemes used in the previous works. We show that
      evolution greatly suppresses herding behavior, and it leads to better overall
      performance of the agents. Similar to the standard nonevolutionary MG, the
      dependence of the standard deviation sigma on the number of agents N and the
      memory length m can be characterized by a universal curve. We suggest a crowd
      anticrowd theory for understanding the effect of evolution in the MG.

PMID- 15244786
TI  - Directed fixed energy sandpile model.
AB  - We numerically study the directed version of the fixed energy sandpile. On a
      closed square lattice, the dynamical evolution of a fixed density of sand grains
      is studied. The activity of the system shows a continuous phase transition around
      a critical density. While the deterministic version has the set of nontrivial
      exponents, the stochastic model is characterized by mean field like exponents.

PMID- 15244787
TI  - Dynamics of stock prices.
AB  - We show that the dynamics of stock prices can be accurately described as a
      continuous time random walk with a time dependent diffusion coefficient. The time
      evolution of the diffusion coefficient can be derived from tick by tick databases
      provided the stock price is characterized in terms of a couple of values
      describing the best ask and the best bid. We are then led to a finding and,
      namely, that the transition rate of the random walk process is different from the
      frequency of transactions. Our results allow us to obtain a fast and reliable
      determination of the diffusion coefficient and precisely confirm that fat tails
      in the distribution of price variations are due to volatility fluctuations.

PMID- 15244788
TI  - Ising model in scale-free networks: a Monte Carlo simulation.
AB  - The Ising model in uncorrelated scale-free networks has been studied by means of
      Monte Carlo simulations. These networks are characterized by a degree (or
      connectivity) distribution P (k) approximately k(-gamma). The ferromagnetic
      paramagnetic transition temperature has been studied as a function of the
      parameter gamma. For gamma>3 our results agree with earlier analytical
      calculations, which found a phase transition at a temperature T(c) (gamma) in the
      thermodynamic limit. For gamma< or =3, a ferromagnetic-paramagnetic crossover
      occurs at a size-dependent temperature T(co), and the system is in the ordered
      ferromagnetic state at any temperature for a system size N--> infinity. For
      gamma=3 and large enough N, the crossover temperature is found to be T(co)
      approximately A ln N, with a prefactor A proportional to the mean degree. For
      2<gamma<3, we obtain T(co) approximately <k>N(z), with an exponent z that
      decreases as gamma increases. This exponent is found to be lower than predicted
      by earlier calculations.

PMID- 15244789
TI  - Synchronization-based estimation of all parameters of chaotic systems from time
      series.
AB  - By a simple combination of adaptive scheme and linear feedback with the updated
      feedback strength, for a large class of chaotic systems it is proved rigorously
      by using the invariance principle of differential equations that all unknown
      model parameters can be estimated dynamically. This approach supplies a
      systematic and analytical procedure for estimating parameters from time series,
      and it is simple to implement in practice. In addition, this method is quite
      robust against the effect of noise and able to respond rapidly to changes in
      operating parameters of the experimental system. Lorenz and Rossler hyperchaos
      systems are used to illustrate the validity of this technique.

PMID- 15244790
TI  - Morphological evolution in the electrodeposition of the Pb-Sn binary system.
AB  - Morphological evolution in the electrodeposition of Pb-Sn binary system is
      studied. As the second component increases, the morphology of the codeposit
      changes from dendrite to ramification, to dense branch, and finally to fractal
      structure, respectively. The evolution arises from the influence of
      crystallographic texture, which leads to a splitting of dendritic tips and the
      formation of ramified morphology. This work provides direct evidence to explore
      the crystallographic influence on the morphological evolution in
      electrodeposition.

PMID- 15244791
TI  - Control of on-off intermittency by slow parametric modulation.
AB  - We study on-off intermittent behavior in two coupled double-well Duffing
      oscillators with stochastic driving and demonstrate that, by using slow harmonic
      modulation applied to an accessible system parameter, the intermittent attractors
      can be completely eliminated. The influence of noise is also investigated. Power
      law scaling of the average laminar time with a critical exponent of -1 as a
      function of both the amplitude and frequency of the control modulation is found
      near the onset of intermittency, which is a signature of on-off intermittency.

PMID- 15244792
TI  - Dust acoustic shock waves.
AB  - It is shown that nonlinear equations governing the dynamics of large amplitude
      nondispersive dust acoustic waves admit nonstationary dust acoustic shock waves.
      Analytical and numerical results for the latter are presented, and the relevance
      of our investigation to laboratory experiments is discussed.

PMID- 15244794
TI  - Resolving an anomaly between measured spectral linewidths of n=3 transitions in N
      II and O III spectra.
AB  - A reported anomaly in the experimental scaling of the widths of Stark broadened
      n=3, Delta n=0 spectral lines along the carbon isoelectronic sequence is not
      observed in the present experiments. The ratio omega(N)/omega(O) of widths for N
      II lines compared to those for the narrower O III lines for the same transitions
      is now measured as lying between two theoretical predictions, both of which show
      a value omega(z-1)/omega(z) greater than unity continuing throughout the
      sequence. In the earlier measurements, the widths (in frequency units) were
      actually measured as being smaller for N II than for O III, i.e., a ratio omega(z
      1)/omega(z) less than unity.

PMID- 15244793
TI  - Streamer branching rationalized by conformal mapping techniques.
AB  - Spontaneous branching of discharge channels is frequently observed, but not well
      understood. We recently proposed a new branching mechanism based on simulations
      of a simple continuous discharge model in high fields. We here present analytical
      results for such streamers in the Lozansky-Firsov limit where they can be modeled
      as moving equipotential ionization fronts. This model can be analyzed by
      conformal mapping techniques which allow the reduction of the dynamical problem
      to finite sets of nonlinear ordinary differential equations. Our solutions
      illustrate that branching is generic for the intricate head dynamics of streamers
      in the Lozansky-Firsov limit.

PMID- 15244795
TI  - Guided elastic waves along a rod defect of a two-dimensional phononic crystal.
AB  - It was shown that elastic waves propagating out-of-plane in a two-dimensional
      phononic crystal can experience full-band-gaps for nonzero values of the wave
      vector component parallel to the rods. By further inserting a rod defect, it is
      demonstrated that modes propagating along the rod defect can be localized within
      the band-gaps of the phononic crystal. Such waveguide modes are exhibited for a
      tungsten/epoxy composite containing an aluminum nitride rod as the rod defect. It
      is expected that guided modes of such a structure can be excited and detected
      electrically owing to the piezoelectric effect.

PMID- 15244796
TI  - Solutions for solitons in nonlinear optically induced lattices.
AB  - We calculate stationary configurations of superposed states "soliton + cnoidal
      wave lattice" of the vector nonlinear Schrodinger equation, using the Darboux
      transformation technique. The obtained expressions contain the Jacobi elliptic
      and theta functions, and are easily manageable. There are five stationary
      configurations, in which one of the defocusing media is stable, while those of
      the focusing medium are classified into two weakly unstable and two unstable. The
      checking of the solutions as well as the construction of their typical shapes is
      accomplished with the help of symbolic package MATHEMATICA.

PMID- 15244797
TI  - Cooling rate, heating rate, and aging effects in glassy water.
AB  - We report a molecular dynamics simulation study of the properties of the
      potential energy landscape sampled by a system of water molecules during the
      process of generating a glass by cooling, and during the process of regenerating
      the equilibrium liquid by heating the glass. We study the dependence of these
      processes on the cooling/heating rates as well as on the role of aging (the time
      elapsed in the glass state). We compare the properties of the potential energy
      landscape sampled during these processes with the corresponding properties
      sampled in the liquid equilibrium state to elucidate under which conditions glass
      configurations can be associated with equilibrium liquid configurations.

PMID- 15244798
TI  - Microstructure in a settling suspension of hard spheres.
AB  - We report direct observations of the structure factor in a settling suspension,
      using numerical simulations based on a lattice-Boltzmann model of the fluid. We
      find that the horizontal density fluctuations in bounded suspensions are strongly
      suppressed by the settling process, vanishing as k(2) at long wavelengths. Our
      measurements of the structure factor confirm the qualitative predictions of one
      of several competing theories, although this theory does not yet explain why
      container walls are so important. Our results contradict the idea that a settling
      suspension is inevitably stratified by hydrodynamic dispersion at the suspension
      supernatent interface.

PMID- 15244799
TI  - Effect of large hydrostatic pressure on the dielectric loss spectrum of type- a
      glass formers.
AB  - New dielectric spectroscopy results are reported for propylene carbonate (PC),
      glycerol, and threitol, measured at very high (1.8 GPa) pressure. These glass
      formers all exhibit an excess wing in their dielectric spectrum above T(g). We
      show that the shape of the alpha peak and excess wing of PC are invariant to
      pressure and temperature, when compared at a fixed value of the alpha -relaxation
      time. However, for the hydrogen-bonded liquids, there is a marked breakdown of
      this temperature-pressure superpositioning, due to a change in chemical structure
      (i.e., concentration of hydrogen bonds) with change of temperature or pressure.
      For all these materials, we can conclude that the excess wing is merely a
      secondary relaxation, masked under ordinary conditions by the intense,
      overlapping alpha peak.

PMID- 15244800
TI  - Generation, propagation, and switching of orientational waves in photoexcited
      liquid-crystalline monolayers.
AB  - Photoinduced orientational waves in illuminated liquid-crystalline monolayers is
      one of the most remarkable far-from-equilibrium phenomena that systems of soft
      condensed matter exhibit. We model this behavior from a phenomenological point of
      view, taking the anisotropic photoexcitation of molecules into account. Numerical
      simulations as well as theoretical analyses of the model reveal that the
      intricate interplay between the spontaneous splay deformation of the liquid
      crystalline order and the anisotropy of the photoexcitation can lead to the
      generation and propagation of orientational waves. The model can explain all the
      salient features of the phenomenon-in particular, the anomalous reversal of the
      propagation direction upon 90 degrees rotation of the polarization direction of
      illumination, which evaded theoretical explanation for nearly a decade.

PMID- 15244801
TI  - Size of outbreaks near the epidemic threshold.
AB  - The spread of infectious diseases near the epidemic threshold is investigated.
      Scaling laws for the size and the duration of outbreaks originating from a single
      infected individual in a large susceptible population are obtained. The maximal
      size of an outbreak n(*) scales as N(2/3) with N the population size. This
      scaling law implies that the average outbreak size [n]scales as N(1/3). Moreover,
      the maximal and the average duration of an outbreak grow as t(*) approximately
      N(1/3) and [t] approximately ln N, respectively.

PMID- 15244802
TI  - Diffusion of hard sphere fluids in disordered media: a molecular dynamics
      simulation study.
AB  - Molecular dynamic simulations are reported for the static and dynamic properties
      of hard sphere fluids in matrices (or media) composed of quenched hard spheres.
      The effect of fluid and matrix density, matrix structure, and fluid to matrix
      sphere size ratio on the static and dynamic properties is studied using
      discontinuous molecular dynamics. The matrix density has a stronger effect on the
      self-diffusion coefficient than the fluid density, especially at high matrix
      densities where the geometric constraints due to the quenched spheres are
      significant. When the ratio of the size of the fluid spheres to that of the
      matrix spheres is equal to or greater than one, the diffusion increases as the
      fluid density is increased, at constant total volume fraction. This trend is
      however reversed if the ratio is smaller than one. Different methods of
      generating the matrix have a very strong effect on the dynamic properties even
      though the static correlations are similar. An analysis of the single-chain
      structure factor of the particle trajectories shows a change in the particle
      diffusive behavior at different time scales, suggestive of a hopping mechanism,
      although normal diffusion is recovered at long times. At high matrix densities,
      there is considerable heterogeneity in the diffusion of the fluid particles. The
      simulations demonstrate that the correlations in the matrix play a significant
      role on the diffusion of fluid spheres. For example, the diffusion constant in
      matrices constructed by different methods can be an order of magnitude different
      even though the pair correlation functions are almost identical.

PMID- 15244803
TI  - Thermodynamics and the glass transition in model energy landscapes.
AB  - We determine the liquid-state thermodynamics for a model energy landscape
      corresponding to soft spheres with a mean-field attraction. We consider two
      approximations, in which the distribution of potential energy minima is either
      Gaussian or binomial, and for each we calculate the liquid spinodal, binodal, and
      "effective" glass transition locus. The resulting models provide a unified
      description of the liquid state across the complete range from low-temperature
      glassiness to high-temperature instability with respect to the vapor phase.

PMID- 15244804
TI  - Slow dynamics in gelation phenomena: from chemical gels to colloidal glasses.
AB  - We here discuss the results of three-dimensional Monte Carlo simulations of a
      minimal lattice model for gelling systems. We focus on the dynamics investigated
      by means of the time autocorrelation function of the density fluctuations and the
      particle mean-square displacement. We start from the case of chemical gelation,
      i.e., with permanent bonds, and characterize the critical dynamics as determined
      by the formation of the percolating cluster, as actually observed in polymer
      gels. By opportunely introducing a finite bond lifetime tau(b), the dynamics
      displays relevant changes and eventually the onset of a glassy regime. This has
      been interpreted in terms of a crossover to dynamics more typical of colloidal
      systems and a connection between classical gelation and recent results on
      colloidal systems is suggested. By systematically comparing the results in the
      case of permanent bonds to finite bond lifetime, the crossover and the glassy
      regime can be understood in terms of effective clusters.

PMID- 15244805
TI  - Macroscopic limit cycle via pure noise-induced phase transitions.
AB  - Bistability generated via a pure noise-induced phase transition is reexamined
      from the view of bifurcations in macroscopic cumulant dynamics. It allows an
      analytical study of the phase diagram in more general cases than previous
      methods. In addition, using this approach we investigate spatially extended
      systems with two degrees of freedom per site. For this system, the analytic
      solution of the stationary Fokker-Planck equation is not available and a standard
      mean field approach cannot be used to find noise-induced phase transitions. A
      different approach based on cumulant dynamics predicts a noise-induced phase
      transition through a Hopf bifurcation leading to a macroscopic limit cycle
      motion, which is confirmed by numerical simulation.

PMID- 15244806
TI  - Modelization of surface diffusion of a molecular dimer.
AB  - A simple model for a dimer molecular diffusion on a crystalline surface, as a
      function of temperature, is presented. The dimer is formed by two particles
      coupled by a quadratic potential. The dimer diffusion is modeled by an overdamped
      Langevin equation in the presence of a two-dimensional periodic potential.
      Numerical simulation's results exhibit some dynamical properties observed, for
      example, in Si2 diffusion on a silicon [100] surface. They can be used to predict
      the value of the effective friction parameter. Comparison between our model and
      experimental measurements is presented.

PMID- 15244807
TI  - Thermalization of an anisotropic granular particle.
AB  - We investigate the dynamics of a needle in a two-dimensional bath composed of
      thermalized point particles. Collisions between the needle and points are
      inelastic and characterized by a normal restitution coefficient alpha<1. By using
      the Enskog-Boltzmann equation, we obtain analytical expressions for the
      translational and rotational granular temperatures of the needle and show that
      these are, in general, different from the bath temperature. The translational
      temperature always exceeds the rotational one, though the difference decreases
      with increasing moment of inertia. The predictions of the theory are in very good
      agreement with numerical simulations of the model.

PMID- 15244808
TI  - Aggregation process on complex networks.
AB  - We study the dynamics of the aggregation of particles and the evolution of the
      mass distribution, on a complex network which is built following the Watts
      Strogatz model. The particles perform random walks following the links on the
      network, and aggregate when they meet other particles. On disordered networks the
      density of particles decays as t(-1), while on regular networks it decays as t(
      1/2). For intermediate levels of network disorder the dynamics follows that of
      regular networks at intermediate density, and for low density the disorder of the
      network becomes relevant and the density decays as t(-1). The crossover time
      between these two regimes scales with network disorder as t approximately p(-2).
      We study also an annealed model for the aggregation process, in which the
      quenched disorder of the network is replaced by stochastic long range jumps in
      the particle dynamics. The annealed model is found to obey a different scaling
      with network disorder, with a crossover time t approximately p(-1).

PMID- 15244809
TI  - Two rubber balloons: phase diagram of air transfer.
AB  - Two identical rubber balloons are partially inflated with air (to different
      extent) and connected by a hose with a valve. It is found that depending on
      initial balloon volumes, when the valve is opened the air will flow either from
      the larger (fuller) balloon to the smaller (emptier) balloon, or from the smaller
      balloon to the larger one. The phenomenon is explained in terms of the nonideal
      rubber elasticity of balloons. The full phase diagram for the air flow dynamics
      is constructed.

PMID- 15244810
TI  - Resonant activation in discrete systems.
AB  - The resonant activation phenomenon (RAP) in a discrete system is studied using
      the master equation formalism. We show that the RAP corresponds to a nonmonotonic
      behavior of the frequency dependent first passage time probability density
      function (PDF). An analytical expression for the resonant frequency is
      introduced, which, together with numerical results, helps understand the RAP
      behavior in the space spanned by the transition rates for the case of reflecting
      and absorbing boundary conditions. The limited range of system parameters for
      which the RAP occurs is discussed. We show that a minimum and a maximum in the
      mean first passage time can be obtained when both boundaries are absorbing.
      Relationships to some biological systems are suggested.

PMID- 15244811
TI  - Noise suppression and spectral decomposition for state-dependent noise in the
      presence of a stationary fluctuating input.
AB  - It recently has been shown that the observed noise amplitude of an intrinsically
      noisy system may be reduced by causing the underlying state to fluctuate [Phys.
      Rev. Lett. 86, 950 (2001)]]. This paper extends the previous theory by
      considering the full power spectrum of the output signal, interpreting noise
      reduction in terms of the low-frequency end of the spectrum as well as the
      integrated spectrum. Our treatment accounts for arbitrarily sized fluctuations
      and deals with both continuous and discretely sampled observations. We show that
      noise suppression is possible if and only if the stationary average of the
      intensity of state-dependent noise decreases. We apply our analysis to an example
      involving saturable electrical conduction discussed in the original paper by
      Vilar and Rubi.

PMID- 15244812
TI  - Frequency dependence and equilibration of the specific heat of glass-forming
      liquids.
AB  - We have performed molecular dynamics simulations on a glass-forming liquid
      consisting of a three-dimensional binary mixture of soft spheres. We show that a
      peak in the specific heat versus temperature can occur because a glassy system
      that shows no signs of aging progresses so slowly through the energy landscape
      that the minimum sampling time needed to obtain accurate thermodynamic averages
      exceeds the observation time. We develop a systematic technique to determine the
      equilibrium value of the specific heat and the minimum sampling time. Below the
      temperature of the specific heat peak, the minimum sampling time is orders of
      magnitude longer than the alpha relaxation time. We find that an equilibrium
      system that is not undergoing structural relaxation or aging has a frequency
      dependent specific heat that rises as the frequency decreases. The rise occurs at
      frequencies corresponding to periods that are long enough for the system to
      sample statistically independent energies. When the period is comparable to the
      minimum sampling time, the frequency dependent specific heat reaches a plateau.
      As a result, the specific heat has a frequency dependence at frequencies orders
      of magnitude lower than is implied by the inverse alpha relaxation time.

PMID- 15244813
TI  - Structural relaxation in supercooled orthoterphenyl.
AB  - We report molecular-dynamics simulation results performed for a model of
      molecular liquid orthoterphenyl in supercooled states, which we then compare with
      both experimental data and mode-coupling-theory (MCT) predictions, aiming at a
      better understanding of structural relaxation in orthoterphenyl. We pay special
      attention to the wave number dependence of the collective dynamics. It is shown
      that the simulation results for the model share many features with experimental
      data for real system, and that MCT captures the simulation results at the
      semiquantitative level except for intermediate wave numbers connected to the
      overall size of the molecule. Theoretical results at the intermediate wave number
      region are found to be improved by taking into account the spatial correlation of
      the molecule's geometrical center. This supports the idea that unusual dynamical
      properties at the intermediate wave numbers, reported previously in simulation
      studies for the model and discernible in coherent neutron-scattering experimental
      data, are basically due to the coupling of the rotational motion to the
      geometrical-center dynamics. However, there still remain qualitative as well as
      quantitative discrepancies between theoretical prediction and corresponding
      simulation results at the intermediate wave numbers, which call for further
      theoretical investigation.

PMID- 15244815
TI  - Gaussian kinetic model for granular gases.
AB  - A kinetic model for the Boltzmann equation is proposed and explored as a
      practical means to investigate the properties of a dilute granular gas. It is
      shown that all spatially homogeneous initial distributions approach a universal
      "homogeneous cooling solution" after a few collisions. The homogeneous cooling
      solution (HCS) is studied in some detail and the exact solution is compared with
      known results for the hard sphere Boltzmann equation. It is shown that all
      qualitative features of the HCS, including the nature of overpopulation at large
      velocities, are reproduced by the kinetic model. It is also shown that all the
      transport coefficients are in excellent agreement with those from the Boltzmann
      equation. Also, the model is specialized to one having a velocity independent
      collision frequency and the resulting HCS and transport coefficients are compared
      to known results for the Maxwell model. The potential of the model for the study
      of more complex spatially inhomogeneous states is discussed.

PMID- 15244814
TI  - Anomalous diffusivity and electric conductivity for low concentration
      electrolytes in nanopores.
AB  - We apply equilibrium and nonequilibrium molecular dynamics simulations to study
      the dynamic properties of electrolytes in nanopores. The realistic primitive
      model and the restrictive primitive model widely used in the statistical
      mechanics of liquid-state theory are applied to model the electrolytes. The
      electrolytic ions are immersed in water, treated in this work as either a
      dielectric continuum ignoring the size of solvent molecules or a macroscopic
      dielectric continuum (polar property) plus neutral soft spheres, and the aqueous
      electrolyte is put in a confined space. To simulate a condition mimicking closely
      processes of practical interest and yet maintaining the simulation
      computationally manageable, we consider an infinitely long and uncharged
      cylindrical tube. The equilibrium property of the self-diffusion coefficient D
      and the nonequilibrium property of electric conductivity sigma are computed in
      terms of electrolyte concentration, particle size, and cylindrical pore radius.
      The simulation results for the continuum solvent restrictive primitive model and
      continuum solvent primitive model show normal behavior for D versus pore radius R
      at ionic concentration 0.1M -i.e., D decreases with decreasing R -display an R
      independence of D at a certain threshold concentration and undergo an anomalous
      increase in D with reducing R at a lower value 0.025 M. The mechanism of the
      anomaly at the ionic concentration 0.025 M was sought for and interpreted in this
      work to arise from the energetic and entropic factors. Our simulated data of
      sigma at this same concentration follow the same trend as D. To delve further
      into the transport properties, we perform simulation studies for the discrete
      solvent primitive model and make a detailed analysis of the characteristic of the
      ion radial density functions. Comparison of the latter functions with those in
      the continuum solvent primitive model sheds light on the simulated diffusion
      coefficient within the context of discrete solvent primitive model which is about
      two orders of magnitude less. This difference in D is naturally attributed to the
      solvent effect. Similar disparities were reported by others for the discrete and
      continuum restrictive primitive models.

PMID- 15244816
TI  - Boundary conditions and defect lines in the Abelian sandpile model.
AB  - We add a defect line of dissipation, or crack, to the Abelian sandpile model. We
      find that the defect line renormalizes to separate the two-dimensional plane into
      two half planes with open boundary conditions. We also show that varying the
      amount of dissipation at a boundary of the Abelian sandpile model does not affect
      the universality class of the boundary condition. We demonstrate that a universal
      coefficient associated with height probabilities near the defect can be used to
      classify boundary conditions.

PMID- 15244817
TI  - Steady-state representation of the homogeneous cooling state of a granular gas.
AB  - The properties of a dilute granular gas in the homogeneous cooling state are
      mapped to those of a stationary state by means of a change in the time scale that
      does not involve any internal property of the system. The new representation is
      closely related with a general property of the granular temperature in the long
      time limit. The physical and practical implications of the mapping are discussed.
      In particular, simulation results obtained by the direct simulation Monte Carlo
      method applied to the scaled dynamics are reported. This includes ensemble
      averages and also the velocity autocorrelation function, as well as the self
      diffusion coefficient obtained from the latter by means of the Green-Kubo
      representation. In all cases, the obtained results are compared with theoretical
      predictions.

PMID- 15244818
TI  - Screening of spherical colloids beyond mean field: a local density functional
      approach.
AB  - We study the counterion distribution around a spherical macroion and its osmotic
      pressure in the framework of the recently developed Debye-Huckel-hole-cavity
      (DHHC) theory. This is a local density functional approach which incorporates
      correlations into Poisson-Boltzmann theory by adding a free energy correction
      based on the one-component plasma. We compare the predictions for ion
      distribution and osmotic pressure obtained by the full theory and by its zero
      temperature limit with Monte Carlo simulations. They agree excellently for weakly
      developed correlations and give the correct trend for stronger ones. In all
      investigated cases the DHHC theory and its computationally simpler zero
      temperature limit yield better results than the Poisson-Boltzmann theory.

PMID- 15244820
TI  - Structural and computational depth of diffusion-limited aggregation.
AB  - Diffusion-limited aggregation (DLA) is studied from the perspective of
      computational complexity. A parallel algorithm is exhibited that requires a
      number of steps that scales as the depth of the tree defined by the cluster. The
      existence of this algorithm suggests a connection between a fundamental
      computational and structural property of DLA.

PMID- 15244819
TI  - Electrokinetic behavior of two touching inhomogeneous biological cells and
      colloidal particles: effects of multipolar interactions.
AB  - We present a theory to investigate electrokinetic behavior, namely,
      electrorotation and dielectrophoresis under alternating current (ac) applied
      fields for a pair of touching inhomogeneous colloidal particles and biological
      cells. These inhomogeneous particles are treated as graded ones with physically
      motivated model dielectric and conductivity profiles. The mutual polarization
      interaction between the particles yields a change in their respective dipole
      moments, and hence in the ac electrokinetic spectra. The multipolar interactions
      between polarized particles are accurately captured by the multiple images
      method. In the point-dipole limit, our theory reproduces the known results. We
      find that the multipolar interactions as well as the spatial fluctuations inside
      the particles can affect the ac electrokinetic spectra significantly.

PMID- 15244821
TI  - Depletion potential in colloidal mixtures of hard spheres and platelets.
AB  - The depletion potential between two hard spheres in a solvent of thin hard
      disclike platelets is investigated by using either the Derjaguin approximation or
      density functional theory. Particular attention is paid to the density dependence
      of the depletion potential. A second-order virial approximation is applied, which
      yields nearly exact results for the bulk properties of the hard-platelet fluid at
      densities two times smaller than the density of the isotropic fluid at isotropic
      nematic phase coexistence. As the platelet density increases, the attractive
      primary minimum of the depletion potential deepens and an additional small
      repulsive barrier at larger sphere separations develops. Upon decreasing the
      ratio of the radius of the spheres and the platelets, the primary minimum
      diminishes and the position of the small repulsive barrier shifts to smaller
      values of the sphere separation.

PMID- 15244822
TI  - Structure of a soft-sphere fluid at a soft repulsive wall: a comparison of
      weighted density-functional theories.
AB  - Density-functional theory is used to investigate the structure of a soft-sphere
      fluid at a soft wall. The fluid is modeled by an inverse sixth-power repulsive
      pair potential and the fluid particles interact with a flat stationary wall
      defined by an inverse-twelth power repulsive external potential. For comparison
      we examine results using three weighted density approximations (WDA), namely
      those due to Phys. Rev. A 32, 2909 (1985)]], Phys. Rev. A 39, 426 (1989)]], and
      the partitioned WDA of Mol. Phys. 90, 951 (1997)]]. The degree to which each of
      these approximations can accurately predict the structure of the fluid at the
      wall is evaluated for several densities through comparison with Monte Carlo
      simulation data.

PMID- 15244823
TI  - Polystyrene thin films in CO(2).
AB  - In air, or vacuum environments, liquid polystyrene (PS) thin films (thickness,
      h<100 nm ) supported by SiOx /Si substrates are structurally metastable or
      unstable, depending on film thickness. They rupture and eventually form droplets
      on the SiOx /Si substrates (dewet) due to the influence of destabilizing long
      ranged van der Waals dispersion forces. We used scanning force microscopy to
      examine the structural stability of liquid PS films in the thickness range 5
      nm<h<100 nm in liquid and in supercritical carbon dioxide ( CO2 ) environments.
      All films in this thickness range were metastable; holes developed throughout the
      films and over time these holes grew, impinged, and eventually formed droplets.
      The rate of destabilization is controlled by three factors: film thickness,
      temperature, and CO2 pressure (which dictates CO2 volume fraction in the films).
      Calculations of the effective interface potentials suggest that the energy
      barrier for nucleation and growth of holes in CO2 is larger than that in air, and
      in the limit of vanishingly low PS volume fraction the films should be stable.

PMID- 15244824
TI  - Epitaxial growth of a colloidal hard-sphere hcp crystal and the effects of
      epitaxial mismatch on crystal structure.
AB  - We demonstrate the epitaxial growth of hard-sphere hcp and double hcp crystals
      using a surface pattern that directly dictates the stacking sequence. A detailed
      three-dimensional analysis based on real-space measurements is performed on
      crystal structure as a function of template-crystal mismatch, which demonstrates
      the possibilities of colloidal epitaxy as a model system for studying the effects
      of a patterned substrate on crystal structure. Perfect template-induced hcp
      crystal growth occurs at an isotropically deformed template. At deformed lattices
      we observe growth of a non-close-packed superstructure and of a perfect (100)
      aligned fcc crystal. Small mismatches lead to increased out-of-plane
      displacements followed by a structural breakup in "crystal" grains where particle
      positions in successive layers are strictly periodic and "defect" grains where
      these positions are displaced with respect to each other. Large mismatches
      prevent crystallization in the surface layers. The volume fraction was found to
      vary drastically (up to about 20% ) as a function of template deformation.

PMID- 15244825
TI  - Spatial persistence and survival probabilities for fluctuating interfaces.
AB  - We report the results of numerical investigations of the steady-state (SS) and
      finite-initial-conditions (FIC) spatial persistence and survival probabilities
      for (1+1) -dimensional interfaces with dynamics governed by the nonlinear Kardar
      Parisi-Zhang equation and the linear Edwards-Wilkinson (EW) equation with both
      white (uncorrelated) and colored (spatially correlated) noise. We study the
      effects of a finite sampling distance on the measured spatial persistence
      probability and show that both SS and FIC persistence probabilities exhibit
      simple scaling behavior as a function of the system size and the sampling
      distance. Analytical expressions for the exponents associated with the power-law
      decay of SS and FIC spatial persistence probabilities of the EW equation with
      power-law correlated noise are established and numerically verified.

PMID- 15244826
TI  - Pattern formation in crystal growth under parabolic shear flow. II.
AB  - Wavy pattern of ice with a specific wavelength occurs during ice growth from a
      thin layer of undercooled water flowing down the surface of icicles or inclined
      plane. In a previous paper [Phys. Rev. E 68, 021603 (2003)]], we have found that
      restoring forces due to gravity and surface tension is a factor for stabilization
      of morphological instability of the solid-liquid interface. However, the
      mechanism for the morphological instability and stability of the solid-liquid
      interface has not been well understood. In the present paper, it is shown that a
      phase difference between fluctuation of the solid-liquid interface and
      distribution of heat flux at the deformed solid-liquid interface, which depends
      on the magnitude of the restoring forces, is a cause of the instability and
      stability of the interface. This mechanism is completely different from the usual
      Mullins-Sekerka instability due to diffusion and stabilization due to the Gibbs
      Thomson effect.

PMID- 15244827
TI  - Kinetic control of surface patterning by laser-induced photochemical deposition
      in liquid solutions. I. Theoretical developments.
AB  - We theoretically analyze the real-time formation of holographic grating driven by
      laser-photochemical deposition in liquid solutions. Considering the one-photon
      excitation of a two-level system, we present a reaction/diffusion description of
      the species produced photochemically by the excitation of a continuous laser
      wave. By assuming that a deposit is heterogeneously nucleated on the substrate
      when concentration of the reaction product reaches solubility, we develop a
      thermodynamic analysis of its late-stage growth under laser irradiation. A rate
      equation is proposed and used to describe the kinetics of three different types
      of patterning: dot array, periodic line writing, and holographic grating formed
      by two interfering beams. In each case, the predicted deposit growth laws show
      the emergence of scaling regimes that give rise to a universal picture of the
      processes involved, whatever the initial photosensitive medium is. Due to the
      crucial role played by patterned coatings in numerous practical applications
      (lithography or holography, for instance), this control in situ of the kinetics
      offers the opportunity to totally monitor the desired patterning. It also
      suggests the way to develop a unified description for holographic grating
      formation driven by photochemical deposition.

PMID- 15244828
TI  - Kinetic control of surface patterning by laser-induced photochemical deposition
      in liquid solutions. II. Experimental investigations.
AB  - We experimentally analyze the real-time formation of periodic surface patterning
      resulting from laser-driven photochemical deposition in liquid solutions. Using
      photochemical deposition of chromium hydroxide layers driven by a continuous Ar+
      laser wave in a potassium chromate solution, we analyze the kinetic formation of
      three different types of patterning: dot array, periodic line writing, and
      holographic grating formed by interfering beams. Results are also presented for
      both flat and curved substrates. In each case, the deposit growth laws are
      measured and they show the emergence of scaling regimes that are predicted by our
      model [Phys. Rev. E 69, 051605 (2004)]]. Data taken from literature are also
      confronted to the model. The observed agreement suggests that a unified picture
      of the processes involved for photodeposition driven by a one-photon absorption
      can be devised, whatever the initial photosensitive medium is. This kinetic
      control of photodeposition, associated to the versatility in monitoring the
      geometry of laser/medium interaction and the flexibility in deposited materials
      by various photochemical reactions, offers a valuable level of development in
      substrate patterning for lithographic or holographic applications.

PMID- 15244829
TI  - Phase-field modeling of binary alloy solidification with coupled heat and solute
      diffusion.
AB  - A phase-field model is developed for simulating quantitatively microstructural
      pattern formation in solidification of dilute binary alloys with coupled heat and
      solute diffusion. The model reduces to the sharp-interface equations in a
      computationally tractable thin-interface limit where (i). the width of the
      diffuse interface is about one order of magnitude smaller than the radius of
      curvature of the interface but much larger than the real microscopic width of a
      solid-liquid interface, and (ii). kinetic effects are negligible. A recently
      derived antitrapping current [Phys. Rev. Lett. 87, 115701 (2001)]] is used in the
      solute conservation equation to recover precisely local equilibrium at the
      interface and to eliminate interface stretching and surface diffusion effects
      that arise when the solutal diffusivities are unequal in the solid and liquid.
      Model results are first compared to analytical solutions for one-dimensional
      steady-state solidification. Two-dimensional thermosolutal dendritic growth
      simulations with vanishing solutal diffusivity in the solid show that both the
      microstructural evolution and the solute profile in the solid are accurately
      modeled by the present approach. Results are then presented that illustrate the
      utility of the model for simulating dendritic solidification for the large ratios
      of the liquid thermal to solutal diffusivities (Lewis numbers) typical of alloys.

PMID- 15244830
TI  - Linear morphological stability analysis of the solid-liquid interface in rapid
      solidification of a binary system.
AB  - The interface stability against small perturbations of the planar solid-liquid
      interface is considered analytically in linear approximation. Following the
      analytical procedure of Trivedi and Kurz [Acta Metall. 34, 1663 (1986)]], which
      is advancing the original treatment of morphological stability by Mullins and
      Sekerka [J. Appl. Phys. 35, 444 (1964)]] to the case of rapid solidification, we
      extend the model by introducing the local nonequilibrium in the solute diffusion
      field around the interface. A solution to the heat- and mass-transport problem
      around the perturbed interface is given in the presence of the local
      nonequilibrium solute diffusion. Using the developing local nonequilibrium model
      of solidification, the self-consistent analysis of linear morphological stability
      is presented with the attribution to the marginal (neutral) and absolute
      morphological stability of a rapidly moving interface. Special consideration of
      the interface stability for the cases of solidification in negative and positive
      thermal gradients is given. A quantitative comparison of the model predictions
      for the absolute morphological stability is presented with regard to experimental
      results of Hoglund and Aziz [D. E. Hoglund and M. J. Aziz, in Kinetics of Phase
      Transformations, edited by M.O. Thompson, M. J. Aziz, and G. B. Stephenson, MRS
      Symposia Proceedings No. 205 (Materials Research Society, Pittsburgh, 1991), p.
      325] on critical solute concentration for the interface breakdown during rapid
      solidification of Si-Sn alloys.

PMID- 15244831
TI  - Anisotropy and nonequilibrium effects on the light scattered from suspension in a
      nematic solvent.
AB  - We investigate the effects produced on the light scattering spectrum by the
      anisotropic diffusion of impurities in an incompressible nematic solvent. The
      spectrum is calculated by using a fluctuating hydrodynamic description when the
      system is both in a fully thermodynamic equilibrium state and in a nonequilibrium
      steady state induced by a dye-concentration gradient. In the former state, the
      isotropic pretransitional phase as well as the nematic phase of the solvent are
      considered. This spectrum is symmetric (Lorentzian) with respect to the frequency
      shifts, but anisotropic through its explicit dependence on the ratio of the
      diffusion coefficients of the dye parallel and normal to the mean molecular axis
      of the nematic. The values of these coefficients were taken from experimental
      measurements of diffusion of methylred and nitrosodimethylaniline in a N -( p 
      methoxybenzylidene)- p -butylaniline (MBBA) solvent. This anisotropy changes the
      height and the width at mid height with respect to the isotropic case in amounts
      which for MBBA vary up to 36% and 26%. We also calculate the spectrum in the
      presence of a concentration gradient of the dye and find that its presence gives
      rise to an asymmetry of the spectrum in its dependence on the frequency shift;
      its maximum increases and is displaced with respect to its equilibrium position.
      The size and direction of this shift are proportional to the magnitude of the dye
      concentration gradient and depend on its relative orientation with respect to the
      scattering vector. For small dimensionless concentration gradients (
      approximately 10(-2) ), this effect is maximum when these vectors are parallel
      and the scattering angle is low ( approximately 1 degrees ). The maximum degree
      of departure from equilibrium is significant and turns out to be approximately
      55%. In view of the significant changes in the spectrum, our theoretical analysis
      suggests that these effects might be observable.

PMID- 15244832
TI  - Isotropic-nematic phase transition in suspensions of filamentous virus and the
      neutral polymer Dextran.
AB  - We present an experimental study of the isotropic-nematic phase transition in an
      aqueous mixture of charged semiflexible rods ( fd virus) and neutral polymer
      (Dextran). A complete phase diagram is measured as a function of ionic strength
      and polymer molecular weight. At high ionic strength we find that adding polymer
      widens the isotropic-nematic coexistence region with polymers preferentially
      partitioning into the isotropic phase, while at low ionic strength the added
      polymer has no effect on the phase transition. The nematic order parameter is
      determined from birefringence measurements and is found to be independent of
      polymer concentration (or equivalently the strength of attraction). The
      experimental results are compared with the existing theoretical predictions for
      the isotropic-nematic transition in rods with attractive interactions.

PMID- 15244833
TI  - Structural transitions in holographic polymer-dispersed liquid crystals.
AB  - Dynamic light scattering was used to analyze the structural and dynamic
      properties of nematic director field within liquid crystal domains formed in
      holographic polymer-dispersed liquid crystal transmission gratings. Samples
      prepared from two different types of prepolymer mixture: one curable with visible
      (VIS) and another curable with UV light were investigated. In both formulations a
      critical slowing down of thermal director fluctuations, signifying the second
      order structural transition of the nematic director field was observed in the
      vicinity of some critical external electric field as well as close to some
      critical temperature. For VIS samples also the size and the shape of phase
      separated droplets and viscoelastic and surface anchoring parameters of the
      liquid crystalline (LC) material forming the droplets were deduced. The
      viscoelastic constants were found to significantly deviate from the viscoelastic
      parameters of the pure LC mixture.

PMID- 15244834
TI  - Splayed polarization in the ferroelectric phase of a bent-core liquid crystal as
      studied by optical second-harmonic generation.
AB  - Splayed polarization orientation has been confirmed in the anticlinic
      ferroelectric phase of a bent-core liquid crystal containing chiral end chains, P
      8 -OPIMB6(*), by optical second-harmonic generation (SHG). The in-plane
      anisotropy of the SHG signal exhibits an unusual six-peak pattern under the
      rotation of parallel polarizers in the absence of an electric field, while a
      usual four-peak pattern simulatable using a uniform molecular orientation model
      is observed under a field. The unusual pattern was explained by considering a
      splayed polarization orientation including the effect of polarization charges.

PMID- 15244835
TI  - Mapping molecular conformation and orientation of polyimide surfaces for
      homeotropic liquid crystal alignment by nonlinear optical spectroscopy.
AB  - Surface-specific sum-frequency vibrational spectroscopy and second-harmonic
      generation were used to study the structures of polyimide (PI) surfaces for
      homeotropic liquid crystal (LC) alignment and the molecular orientation of LC
      adsobates on these surfaces. The imide ring was perpendicular to the surface with
      one of CO bonds protruding out of the surface and the other pointing into the
      bulk rather than flat on the surface. The ester CO bond in the side chain was
      sticking out of the surface with a tilt angle of about 45 degrees -55 degrees
      from the surface normal, indicating that the rigid side chain core was, more or
      less, along the surface normal. The part of alkyl chain on the top of the side
      chain followed the orientation of the side chain core and protruded out of the
      surface with some gauche defects. The cyano biphenyl LC molecules were adsorbed
      on the PI preferentially with the terminal cyano group facing the PI surface.

PMID- 15244836
TI  - X-ray and dielectric measurements of the smectic- A -hexatic- B transitionin bulk
      and confined geometries.
AB  - We report x-ray and dielectric measurements on a liquid crystal exhibiting a
      smectic- A -hexatic- B (Sm- A -Hex- B ) transition in bulk and confined
      geometries. The confined geometry experiments have been performed by filling the
      compound, n -butyl 4(') - n -hexyloxybiphenyl-4-carboxylate, into Anopore
      membranes with 20 nm pore size. The surprising result seen in the x-ray studies
      on both the bulk and the Anopore samples is the presence of unusually strong
      second harmonic reflection arising from the smectic layers in both the Sm- A and
      Hex- B phases. In fact, the third harmonic reflection is also observed in the
      entire temperature range of the Hex- B phase and close to the transition in the
      Sm- A phase of the bulk sample, with the ratio of I(2qo) / I(qo), and I(3qo) /
      I(qo) being approximately 1/40 and 1/470, respectively (here I(qo), I(2qo), and
      I(3qo) correspond to the peak intensities of the first, second, and third
      harmonic reflections). These features point to the fact that the layering is much
      better defined in this system, unlike the usual description of pure sinusoidal
      mass density wave with a typical value of 10(-4) for I(2qo) / I(qo). Another
      notable feature observed is that whereas the extent of positional correlations of
      the molecules within the smectic layer, is comparable in the Sm- A phase of the
      bulk and Anopore samples, the correlations are reduced in the Hex- B phase. In
      the bulk as well as the Anopore case, the critical behavior of the positional
      correlations is found to be well described by a power-law expression with the
      exponent alpha being slightly larger for the Anopore sample. It is also seen that
      the weak first order nature of the transition seen in the bulk, gets weakened
      further, perhaps becoming second order. Despite such significant differences
      between the bulk and Anopore samples, the dynamics associated with the director
      fluctuations is only slightly influenced by confinement.

PMID- 15244837
TI  - Anomalous intensity dependence of optical reorientation in azo-dye-doped nematic
      liquid crystals.
AB  - The intensity dependence of optical nonlinearity in a nematic liquid crystal
      doped with an azo-dye is investigated. The reorientational part of the
      nonlinearity changes from self-defocusing to self-focusing character while the
      intensity passes through the saturation value of trans-cis photoisomerization.
      This observation, in accordance with previous models, indicates that the optical
      torque generated by the trans-isomers is of opposite sign than the torque
      generated by the cis-isomers. At very low intensities a further reorientational
      nonlinearity was found, which is attributed to light-induced orientational
      redistribution of adsorbed molecules at the surface.

PMID- 15244838
TI  - Influence of the ions on the dynamical response of a nematic cell submitted to a
      dc voltage.
AB  - The influence of the ions present in a liquid crystal on the dynamical response
      of a nematic slab submitted to a dc voltage is studied. The evolution of the
      system toward the equilibrium state is investigated by solving the continuity
      equation for the electric charge, taking into account the current of drift and of
      diffusion. Our analysis shows that the formation of the double layers close to
      the electrodes strongly modifies the distribution of the electric field across
      the sample. We evaluate the surface polarization due to the ions movements and
      the contribution to the anisotropic part of the surface energy having a
      dielectric origin. We show also that, even if the optical response of the liquid
      crystal is a slow phenomenon, the distribution of the ionic charge is rather
      fast. Consequently, the presence of the ions cannot be neglected in the
      determination of the flexoelectric coefficients when the nematic sample is
      submitted to a square wave having a period of the order of 1 s.

PMID- 15244839
TI  - Pretransitional anomalies in the shear flow near a second-order nematic-smectic-
      a phase change.
AB  - Pretransitional anomalies in a shear flow near a second order nematic-smectic- A
      ( NA ) phase transition temperature T(NA), for liquid crystals (LC's), taking
      into account the fluctuations of the local smectic order parameter above the
      T(NA), are investigated. It is shown that the tumbling instability of the Couette
      shear flow for polar LC compounds, such as 4-n-octyl- 4(') -cyanobiphenyl (8CB),
      in the vicinity of T(NA), e.g., at a few tens of mK from T(NA) in the nematic
      phase, occurs at any shear rate gamma;.

PMID- 15244840
TI  - Dynamics of nematic elastomers.
AB  - We study the low-frequency, long-wavelength dynamics of soft and semisoft nematic
      elastomers using two different but related dynamic theories. Our first
      formulation describes the pure hydrodynamic behavior of nematic elastomers in
      which the nematic director has relaxed to its equilibrium value in the presence
      of strain. We find that the sound-mode structure for soft elastomers is identical
      to that of columnar liquid crystals. Our second formulation generalizes the
      derivation of the equations of nematohydrodynamics by Forster et al. to nematic
      elastomers. It treats the director explicitly and describes slow modes beyond the
      hydrodynamic limit.

PMID- 15244841
TI  - Energy-landscape-model analysis for irreversibility and its pulse-width
      dependence in cells subjected to a high-intensity ultrashort electric pulse.
AB  - We provide a simple, but physical analysis for cell irreversibility and apoptosis
      in response to an ultrashort (nanosecond), high-intensity electric pulse. Our
      approach is based on an energy landscape model for determining the temporal
      evolution of the configurational probability function p(q). The primary focus is
      on obtaining qualitative predictions of a pulse width dependence to apoptotic
      cell irreversibility that has been observed experimentally. The analysis couples
      a distributed electrical model for current flow with the Smoluchowski equation to
      provide self-consistent, time-dependent transmembrane voltages. The model
      captures the essence of the experimentally observed pulse-width dependence, and
      provides a possible physical picture that depends only on the electrical trigger.
      A number of interesting features are predicted.

PMID- 15244842
TI  - Elastic deformations of grafted layers with surface stress.
AB  - We calculate the elastic response of thin films grafted to a solid substrate
      whose upper surface is subject to a stress. This issue is addressed in the
      context of biological cell adhesion where adhesive junctions consist of a thin
      layer of proteins grafted to the extracellular matrix and sheared by the cell
      contractility apparatus. We show that the finite thickness of the layer limits
      stress-induced deformations to short ranges proportional to the thickness of the
      film. In addition, we show that the attachment boundary condition creates an
      effective shear response to surface stresses that couples all the directions,
      even for fluidlike layers. We predict that perturbations with wavelengths of
      order of the film thickness induce resonancelike responses for isotropic
      rubberlike materials or anisotropic media with high shear moduli. We use these
      results to predict the elastic deformations of a layer of proteins under shear
      stress and propose that the resulting, polarized elastic response to local
      surface forces can explain the observed, anisotropic growth of cell-substrate
      junctions when subject to external stresses.

PMID- 15244843
TI  - Models to analyze small-angle neutron scattering from unilamellar lipid vesicles.
AB  - Small-angle scattering has been employed to study the structure of lipid bilayers
      in unilamellar vesicles. This paper evaluates the use of a model approach for the
      analysis of such data. A long molecular dynamics simulation of a
      dipalmitoylphosphatidylcholine bilayer in the L(alpha) phase provides detailed
      structural information from which scattering length density profiles and
      scattering intensity are obtained. A sequence of increasingly realistic models
      are defined and then fit to the simulated scattering intensity data for values of
      q that are experimentally accessible. The models are evaluated by how well they
      fit the intensity data and the structural parameters of the simulation. Although
      the conventional approach that extracts only the radius of gyration from a Kratky
      Porod plot provides a reasonable fit to much of the data, the available
      experimental q range supports refined models with two independent parameters. Of
      the many two-parameter models, we propose that particular choices should be
      inspired by the functional form of the scattering length density profile of
      simulations. Constraints that limit realistic models to two independent
      parameters are described in detail. The analysis supports the proposition that
      reliable results for area/lipid and hydrocarbon thickness can be obtained from
      small-angle neutron scattering of unilamellar vesicles.

PMID- 15244844
TI  - Phase transition of traveling waves in bacterial colony pattern.
AB  - Depending on the growth condition, bacterial colonies can exhibit different
      morphologies. Many previous studies have used reaction diffusion equations to
      reproduce spatial patterns. They have revealed that nonlinear reaction term can
      produce diverse patterns as well as nonlinear diffusion coefficient. Typical
      reaction term consists of nutrient consumption, bacterial reproduction, and
      sporulation. Among them, the functional form of sporulation rate has not been
      biologically investigated. Here we report experimentally measured sporulation
      rate. Then, based on the result, a reaction diffusion model is proposed. One
      dimensional simulation showed the existence of traveling wave solution. We study
      the wave form as a function of the initial nutrient concentration and find two
      distinct types of solution. Moreover, transition between them is very sharp,
      which is analogous to phase transition. The velocity of traveling wave also shows
      sharp transition in nonlinear diffusion model, which is consistent with the
      previous experimental result. The phenomenon can be explained by separatrix in
      reaction term dynamics. Results of two-dimensional simulation are also shown and
      discussed.

PMID- 15244845
TI  - Dynamics of the minimally frustrated helices determine the hierarchical folding
      of small helical proteins.
AB  - In this paper we aim at determining the key residues of small helical proteins in
      order to build up reduced models of the folding dynamics. We start by arguing
      that the folding process can be dissected into concurrent fast and slow dynamics.
      The fast events are the quasiautonomous coil-to-helix transitions occurring in
      the minimally frustrated initiation sites of folding in the early stages of the
      process. The slow processes consist in the docking of the fluctuating helices
      formed in these critical sites. We show that a neural network devised to predict
      native secondary structures from sequence can be used to estimate the
      probabilities of formation of these helical traits as they are embedded in the
      protein. The resulting probabilities are shown to correlate well with the
      experimental helicities measured in the same isolated peptides. The relevance of
      this finding to the hierarchical character of folding is confirmed within the
      framework of a diffusion-collision-like mechanism. We demonstrate that
      thermodynamic and topological features of these critical helices allow accurate
      estimation of the folding times of five proteins that have been kinetically
      studied. This suggests that these critical helices determine the fundamental
      events of the whole folding process. A remarkable feature of our model is that
      not all of the native helices are eligible as critical helices, whereas the whole
      set of the native helices has been used so far in other reconstructions of the
      folding mechanism. This stresses that the minimally frustrated helices of these
      helical proteins comprise the minimal set of determinants of the folding process.

PMID- 15244846
TI  - Dynamics of biological molecules irradiated by short x-ray pulses.
AB  - Very short and intense x-ray pulses can be used for diffraction imaging of single
      biological molecules. Inevitably, x-ray absorption initiates damage that degrades
      the molecule's image. This paper presents a continuum model of the physics that
      leads to damage when a small particle absorbs a large x-ray dose. The main
      processes are found to be ionization and Coulomb-force driven atomic motion.
      Trapping of electrons, Debye shielding, and nonuniform collisional ionization all
      have a significant effect on the overall damage kinetics.

PMID- 15244847
TI  - Polymer-induced bundling of F actin and the depletion force.
AB  - The inert polymer polyethylene glycol (PEG) induces a "bundling" phenomenon in F
      actin solutions when its concentration exceeds a critical onset value C(o). Over
      a limited range of PEG molecular weight and ionic strength, C(o) can be expressed
      as a function of these two variables. The process is reversible, but hysteresis
      is also observed in the dissolution of the bundles, with ionic strength having a
      large influence. Additional actin filaments are able to join the previously
      formed bundles. PEG polymers are not incorporated into the actin bundles.
      Estimates of the Asakura-Oosawa depletion force, Coulomb repulsion, and van der
      Waals potential are combined in order to explain the bundling effect and
      hysteresis. Conjectures are presented concerning the apparent limit in bundle
      size.

PMID- 15244848
TI  - Sampling tissue volumes using frequency-domain photon migration.
AB  - We demonstrate the use of Monte Carlo simulations to generate photon scattering
      density functions (PSDFs) that represent the tissue volume sampled by steady
      state and frequency-domain photon migration. We use these results to illustrate
      how scaling laws can be developed to determine the mean sampling depth of the
      multiply scattered photons detected by photon migration methods that remain valid
      outside the bounds of the standard diffusion approximation, i.e., at small source
      detector separations and in media where the optical absorption is significant
      relative to scattering. Using both the PSDF computation and the newly formulated
      scaling laws, we focus on a comprehensive description of the effects of source
      modulation frequency, optical absorption, and source-detector separation on the
      depth of the sampled tissue volume as well as the sensitivity of frequency-domain
      photon migration measurements to the presence of a localized absorption
      heterogeneity.

PMID- 15244849
TI  - Transmission of stimulus-locked responses in two coupled phase oscillators.
AB  - A model of two n:m coupled phase oscillators is studied, where both oscillators
      are subject to random forces, but only one oscillator is repetitively stimulated
      with a pulsatile stimulus. The focus of the paper is on transmission of transient
      responses as well as transient synchronization and desynchronization, which are
      stimulus locked, i.e., tightly time locked to the stimulus. A bistability or
      multistability of stable synchronized states of the two-phase oscillators (modulo
      2pi ) occurs due to the n:m coupling. Accordingly, after stimulation the two
      oscillators may tend to qualitatively different stable states, which leads to a
      cross-trial (CT) response clustering (i.e., a switching between qualitatively
      different poststimulus responses across trials) of either one of the oscillators
      or both. A stochastic CT phase resetting analysis allows one to detect such
      transient responses and provides a reliable estimation of the transmission time.
      In contrast, CT averaging (averaging over an ensemble of responses), CT standard
      deviation, and CT cross correlation fail in studying the transmission of such
      stimulus-locked responses, even in the simpler case of 1:1 coupling. In
      particular, even though being used as golden standard for the analysis of evoked
      responses in medicine and neuroscience, CT averaging typically causes severe
      artifacts and misinterpretations.

PMID- 15244850
TI  - Percolation and Burgers' dynamics in a model of capillary formation.
AB  - Capillary networks are essential in vertebrates to supply tissues with nutrients.
      Experiments of in vitro capillary formation show that cells randomly spread on a
      gel matrix autonomously organize to form vascular networks. Cells form
      disconnected networks at low densities and connected ones above a critical
      density. Above the critical density the network is characterized by a typical
      mesh size approximately 200 microm, which is approximately constant on a wide
      range of density values. In this paper we present a full characterization of a
      recently proposed model which reproduces the main features of the biological
      system, focusing on its dynamical properties, on the fractal properties of
      patterns, and on the percolative phase transition. We discuss the relevance of
      the model in relation with some experiments in living beings and proposed
      diagnostic methods based on the measurement of the fractal dimension of vascular
      networks.

PMID- 15244851
TI  - Analytical study of the effect of recombination on evolution via DNA shuffling.
AB  - DNA shuffling is an evolutionary protocol wherein cycles of selection,
      recombination, mutation, and amplification are employed to evolve proteins and
      DNA sequences. Experiments have shown its superiority to traditional protocols
      which do not employ recombination. Motivated by DNA shuffling, we investigate a
      multilocus evolutionary model that incorporates selection, recombination, and
      point mutations. Due to simplicity of the model, for the case of an infinite
      population we can obtain a full analytical treatment of both its dynamical and
      equilibrium properties, and study the benefit of recombination explicitly and
      quantitatively. We also briefly discuss finite-population size corrections.

PMID- 15244852
TI  - Role of evolution by natural selection in population dynamics.
AB  - Using a Monte Carlo approach we study the role of inheritance and natural
      selection in the dynamics of populations. We show that a population subject to
      inheritance has a much better chance of survival in a given condition than a
      population where new generations do not inherit genomes of their parents. The
      dependence of the survival chance on such factors as selection pressure,
      fecundity, or carrying capacity of the system is much stronger when selection and
      inheritance are present. We demonstrate, in accordance with biological
      observations, that in certain conditions evolution can save a population which
      would perish without it.

PMID- 15244853
TI  - Adaptation and enslavement in endosymbiont-host associations.
AB  - The evolutionary persistence of symbiotic associations is a puzzle. Adaptation
      should eliminate cooperative traits if it is possible to enjoy the advantages of
      cooperation without reciprocating-a facet of cooperation known in game theory as
      the Prisoner's Dilemma. Despite this barrier, symbioses are widespread and may
      have been necessary for the evolution of complex life. The discovery of
      strategies such as tit-for-tat has been presented as a general solution to the
      problem of cooperation. However, this only holds for within-species cooperation,
      where a single strategy will come to dominate the population. In a symbiotic
      association each species may have a different strategy, and the theoretical
      analysis of the single-species problem is no guide to the outcome. We present
      basic analysis of two-species cooperation and show that a species with a fast
      adaptation rate is enslaved by a slowly evolving one. Paradoxically, the rapidly
      evolving species becomes highly cooperative, whereas the slowly evolving one
      gives little in return. This helps understand the occurrence of endosymbioses
      where the host benefits, but the symbionts appear to gain little from the
      association.

PMID- 15244854
TI  - Adaptive time-frequency parametrization of epileptic spikes.
AB  - Adaptive time-frequency approximations of signals have proven to be a valuable
      tool in electroencephalogram (EEG) analysis and research, where it is believed
      that oscillatory phenomena play a crucial role in the brain's information
      processing. This paper extends this paradigm to the nonoscillating structures
      such as the epileptic EEG spikes, and presents the advantages of their
      parametrization in general terms such as amplitude and half-width. A simple
      detector of epileptic spikes in the space of these parameters, tested on a
      limited data set, gives very promising results. It also provides a direct
      distinction between randomly occurring spikes or spike/wave complexes and
      rhythmic discharges.

PMID- 15244855
TI  - Patterns in syntactic dependency networks.
AB  - Many languages are spoken on Earth. Despite their diversity, many robust language
      universals are known to exist. All languages share syntax, i.e., the ability of
      combining words for forming sentences. The origin of such traits is an issue of
      open debate. By using recent developments from the statistical physics of complex
      networks, we show that different syntactic dependency networks (from Czech,
      German, and Romanian) share many nontrivial statistical patterns such as the
      small world phenomenon, scaling in the distribution of degrees, and
      disassortative mixing. Such previously unreported features of syntax organization
      are not a trivial consequence of the structure of sentences, but an emergent
      trait at the global scale.

PMID- 15244856
TI  - Discerning aggregation in homogeneous ensembles: a general description of photon
      counting spectroscopy in diffusing systems.
AB  - In order to discern aggregation in solution, we present a quantum mechanical
      analog of the photon statistics from fluorescent molecules diffusing through a
      focused beam. A generating functional is developed to fully describe the
      experimental physical system as well as the statistics. Histograms of the
      measured time delay between photon counts are fit by an analytical solution
      describing the static as well as diffusing regimes. To determine empirical
      fitting parameters, fluorescence correlation spectroscopy is used in parallel to
      the photon counting. For expedient analysis, we find that the distribution's
      deviation from a single Poisson shows a difference between two single fluor
      monomers or a double fluor aggregate of the same total intensities. Initial
      studies were performed on fixed-state aggregates limited to dimerization. However
      preliminary results on reactive species suggest that the method can be used to
      characterize any aggregating system.

PMID- 15244857
TI  - Folding and form: insights from lattice simulations.
AB  - Monte Carlo simulations of a Miyazawa-Jernigan lattice-polymer model indicate
      that, depending on the native structure's geometry, the model exhibits two broad
      classes of folding mechanisms for two-state folders. Folding to native structures
      of low contact order is driven by backbone distance and is characterized by a
      progressive accumulation of structure towards the native fold. By contrast,
      folding to high contact order targets is dominated by intermediate stage contacts
      not present in the native fold, yielding a more cooperative folding process.

PMID- 15244858
TI  - Effects of synaptic conductance on the voltage distribution and firing rate of
      spiking neurons.
AB  - A neuron in an active cortical circuit is subject to a fluctuating synaptic drive
      mediated by conductance changes. It was recently demonstrated that synaptic
      conductance effects in vivo significantly alter the integrative properties of
      neurons. These effects are missed in models that approximate the synaptic drive
      as a fluctuating current. Here the membrane-potential distribution and firing
      rate are derived for the integrate-and-fire neuron with delta correlated
      conductance-based synaptic input using the Fokker-Planck formalism. A number of
      different input scenarios are examined, including balanced drive and fluctuation
      changes at constant conductance, the latter of which corresponds to shifts in
      synchrony in the presynaptic population. This minimal model captures many
      experimentally observed conductance-related effects such as reduced membrane
      potential fluctuations in response to increasing synaptic noise. The solvability
      of the model allows for a direct comparison with current-based approaches,
      providing a basis for assessing the validity of existing approximation schemes
      that have dealt with conductance change. In particular, a commonly used heuristic
      approach, whereby the passive membrane time constant is replaced by a drive
      dependent effective time constant, is examined. It is demonstrated that this
      approximation is valid in the same limit that the underlying diffusion
      approximation holds, both for delta correlated as well as filtered synaptic
      drive.

PMID- 15244859
TI  - Hierarchical structure in healthy and diseased human heart rate variability.
AB  - It is shown that the healthy and diseased human heart rate variability (HRV)
      possesses a hierarchical structure of the She-Leveque (SL) form. This structure,
      first found in measurements in turbulent fluid flows, implies further details in
      the HRV multifractal scaling. The potential of diagnosis is also discussed based
      on the characteristics derived from the SL hierarchy.

PMID- 15244860
TI  - Theoretical and computational methods for the noninvasive detection of gastric
      electrical source coupling.
AB  - The ability to study the pathology of the stomach noninvasively from magnetic
      field measurements is important due to the significant practical advantages
      offered by noninvasive methods over other techniques of investigation. The
      inverse biomagnetic problem can play a central role in this process due to the
      information that inverse solutions can yield concerning the characteristics of
      the gastric electrical activity (GEA). To analyze gastrointestinal (GI) magnetic
      fields noninvasively, we have developed a computer implementation of a least
      squares minimization algorithm that obtains numerical solutions to the
      biomagnetic inverse problem for the stomach. In this paper, we show how electric
      current propagation and the mechanical coupling of gastric smooth muscle cells
      during electrical control activity can be studied using such solutions. To
      validate our model, two types of numerical simulations of the GEA were developed
      and successfully used to demonstrate the ability of our computer algorithm to
      detect and accurately analyze these two phenomena. We also describe our analysis
      of experimental, noninvasively acquired gastric biomagnetic data as well as the
      information of interest that our numerical method can yield in clinical studies.
      Most importantly, we present experimental evidence that the coupling of gastric
      electrical sources can be observed using noninvasive techniques of measurement,
      in our case with the use of a superconducting quantum interference device
      magnetometer. We discuss the relevance and implications of our achievement to the
      future of GI research.

PMID- 15244861
TI  - Effect of intracrystalline water on longitudinal sound velocity in tetragonal hen
      egg-white lysozyme crystals.
AB  - Longitudinal sound velocity of tetragonal hen-egg-white (HEW) lysozyme crystals
      was measured during air drying by ultrasonic pulseecho method. The sound velocity
      increases with exposure to open air and approaches a constant value. The maximum
      value is approximately 2900 m/s that is about 1.6 times as much as that of
      original one before drying. In addition, the sound velocity clearly recovers to
      original one after immersing the dried crystal in solution. Therefore, the sound
      velocity in tetragonal HEW lysozyme crystals can be reversibly changed due to
      dehydration and rehydration. These changes in sound velocity are discussed in the
      light of water-mediated intramolecular and intermolecular interactions in the
      crystals.

PMID- 15244862
TI  - Clusters in a magnetic toy model for binary granular piles.
AB  - Results on a generalized magnetically controlled ballistic deposition model of
      granular piles are reported in order to search for the effect of "spin flip"
      probability q in building a granular pile. Two different regimes of spin cluster
      site distributions have been identified, a borderline q(c) (betaJ) where J is the
      interaction potential strength.

PMID- 15244863
TI  - Structure of nonuniform polymer melts: density functional perturbation approach.
AB  - A density functional perturbation approximation for polyatomic molecules, which
      is based on the fundamental-measure theory for hard-core repulsion and the hybrid
      weighted-density approximation for chain connectivity, was proposed to clarify
      the structure of polymer melts at interfaces. It was applied to predict the local
      density distributions, adsorption isotherms, and surface excess of a freely
      jointed tangent hard-sphere chain in hard slit pores. Wertheim's first-order
      perturbation theory extended by J. Chem. Phys. 112, 2368 (2002)] was used to
      calculate the weight function and second-order direct correlation function due to
      the chain connectivity. The theoretical results are in excellent agreement with
      the computer simulations.

PMID- 15244864
TI  - Generalized survival in equilibrium step fluctuations.
AB  - We investigate the dynamics of a generalized survival probability S(t,R) defined
      with respect to an arbitrary reference level R (rather than the average) in
      equilibrium step fluctuations. The exponential decay at large time scales of the
      generalized survival probability is numerically analyzed. S(t,R) is shown to
      exhibit simple scaling behavior as a function of system size L, sampling time
      deltat, and the reference level R. The generalized survival time scale tau(s) (R)
      associated with S(t,R) is shown to decay exponentially as a function of R.

PMID- 15244865
TI  - Equilibrium of anchored interfaces with quenched disordered growth.
AB  - The roughening behavior of a one-dimensional interface fluctuating under quenched
      disorder growth is examined while keeping an anchored boundary. The latter
      introduces detailed balance conditions which allows for a simple but thorough
      analysis of equilibrium aspects at both macroscopic and microscopic scales. It is
      found that the interface roughens linearly with the substrate size only in the
      vicinity of special disorder realizations. Otherwise, it remains stiff and
      tilted.

PMID- 15244866
TI  - Numerical evidence for stretched exponential relaxations in the Kardar-Parisi
      Zhang equation.
AB  - We present results from extensive numerical integration of the Kardar-Parisi
      Zhang (KPZ) equation in 1+1 dimensions aimed to check the long-time behavior of
      the dynamical structure factor of that system. Over a number of decades in the
      size of the structure factor we confirm scaling and stretched exponential decay.
      We also give an analytic expression that yields a very good approximation to the
      numerical data. Our result clearly favors stretched exponential decay over recent
      results claiming to yield the exact time dependent structure factor of the 1+1 
      dimensional KPZ system. We suggest a possible solution to that contradiction.

PMID- 15244867
TI  - Comment on "Mechanical analog of temperature for the description of force
      distribution in static granular packings".
AB  - It has been proposed by Ngan [Phys. Rev. E 68, 011301 (2003)] that the granular
      contact force distribution may be analytically derived by minimizing the analog
      of a thermodynamic free energy, in this case consisting of the total potential
      energy stored in the compressed contacts minus a particular form of entropy
      weighted by a parameter. The parameter is identified as a mechanical temperature.
      I argue that the particular form of entropy cannot be correct and as a result the
      proposed method produces increasingly errant results for increasing grain
      rigidity. This trend is evidenced in Ngan's published results and in other
      numerical simulations and experiments.

PMID- 15244869
TI  - Efficiency and reliability of epidemic data dissemination in complex networks.
AB  - We study the dynamics of epidemic spreading processes aimed at spontaneous
      dissemination of information updates in populations with complex connectivity
      patterns. The influence of the topological structure of the network in these
      processes is studied by analyzing the behavior of several global parameters, such
      as reliability, efficiency, and load. Large-scale numerical simulations of update
      spreading processes show that while networks with homogeneous connectivity
      patterns permit a higher reliability, scale-free topologies allow for a better
      efficiency.

PMID- 15244870
TI  - Quantum dissipation due to the interaction with chaos.
AB  - We discuss the possibility of having "quantum dissipation" due to the interaction
      with chaotic degrees of freedom. We define the conditions that should be
      satisfied in order to have a dissipative effect similar to the one due to an
      interaction with a (many body) bath. We also compare with the case where the
      environment is modeled by a random matrix model. In the case of interaction with
      "chaos" we observe a regime where the relaxation process is nonuniversal and
      reflects the underlaying semiclassical dynamics. As an example we consider a two
      level system (spin) that interacts with a two-dimensional anharmonic oscillator.

PMID- 15244871
TI  - Characteristics of a delayed system with time-dependent delay time.
AB  - The characteristics of a time-delayed system with time-dependent delay time is
      investigated. We demonstrate that the nonlinearity characteristics of the time
      delayed system are significantly changed depending on the properties of time
      dependent delay time and especially that the reconstructed phase trajectory of
      the system is not collapsed into simple manifold, differently from the delayed
      system with fixed delay time. We discuss the possibility of a phase space
      reconstruction and its applications.

PMID- 15244872
TI  - Bernstein-Greene-Kruskal solitary waves in three-dimensional magnetized plasma.
AB  - We study the width-amplitude relation for three-dimensional Bernstein-Greene
      Kruskal (BGK) electrostatic solitary waves in magnetized plasmas, taking into
      account the dynamics of both electrons and ions. We obtain two coupled
      inequalities that constrain the amplitude and the widths parallel and
      perpendicular to the magnetic field for a Gaussian potential, and demonstrate how
      the solution space is further constrained by the finite temperature ratio between
      electrons and ions. The description is valid for both the electron and ion mode
      solitary waves. Our results provide a quantitative basis for understanding the
      ubiquity of BGK waves in widely different classes of collisionless plasmas.

PMID- 15244873
TI  - Prediction of simultaneously large and opposite generalized Goos-Hanchen shifts
      for TE and TM light beams in an asymmetric double-prism configuration.
AB  - It is predicted that large and opposite generalized Goos-Hanchen (GGH) shifts may
      occur simultaneously for TE and TM light beams upon reflection from an asymmetric
      double-prism configuration when the angle of incidence is below but near the
      critical angle for total reflection, which may lead to interesting applications
      in optical devices and integrated optics. Numerical simulations show that the
      magnitude of the GGH shift can be of the order of beam's width.

PMID- 15244874
TI  - Controlling light by light in a one-dimensional resonant photonic crystal.
AB  - We consider the interaction and stability of gap solitons in a one-dimensional,
      resonant, photonic crystal with a defect state produced by a linear localized
      mode, or by an incoherent pump. Soliton propagation is investigated using both an
      analytical treatment and the direct numerical integration of the two-wave Maxwell
      Bloch equations. Our results demonstrate that the soliton can be trapped,
      reflected from, or tunnel through the defect state.

PMID- 15244875
TI  - Improved extremal optimization for the Ising spin glass.
AB  - A version of the extremal optimization (EO) algorithm introduced by Boettcher and
      Percus is tested on two- and three-dimensional spin glasses with Gaussian
      disorder. EO preferentially flips spins that are locally "unfit"; the variant
      introduced here reduces the probability of flipping previously selected spins.
      Relative to EO, this adaptive algorithm finds exact ground states with a speedup
      of order 10(4) (10(2) ) for 16(2) - (8(3) -) spin samples. This speedup increases
      rapidly with system size, making this heuristic a useful tool in the study of
      materials with quenched disorder.

PMID- 15244876
TI  - Entropy of pseudo-random-number generators.
AB  - Since the work of Phys. Rev. Lett. 69, 3382 (1992)]] some pseudo-random-number
      generators are known to yield wrong results in cluster Monte Carlo simulations.
      In this contribution the fundamental mechanism behind this failure is discussed.
      Almost all random-number generators calculate a new pseudo-random-number x(i)
      from preceding values, x(i) =f( x(i-1), x(i-2), ..., x(i-q) ). Failure of these
      generators in cluster Monte Carlo simulations and related experiments can be
      attributed to the low entropy of the production rule f() conditioned on the
      statistics of the input values x(i-1), ..., x(i-q). Being a measure only of the
      arithmetic operations in the generator rule, the conditional entropy is
      independent of the lag in the recurrence or the period of the sequence. In that
      sense it measures a more profound quality of a random-number generator than
      empirical tests with their limited horizon.

PMID- 15244877
TI  - Scaling law in target-hunting processes.
AB  - We study a hunting process for a target, in which the hunter tracks the goal by
      smelling odors it emits. The odor intensity is supposed to decrease with the
      diffusion distance. The Monte Carlo experiment is carried out on a two
      dimensional square lattice. Having no idea of the location of the target, the
      hunter determines its moves only by random attempts in each direction. By sorting
      the searching time in each simulation and introducing a variable x to reflect the
      sequence of searching times, we obtain a curve with a wide plateau, indicating
      the most probable time of successfully finding the target. The simulations reveal
      a scaling law for the searching time versus the distance to the position of the
      target. The scaling exponent depends on the sensitivity of the hunter. Our model
      may be a prototype in studying such searching processes as various food-foraging
      behaviors of wild animals.

PMID- 15244878
TI  - Random matrix approach to multivariate correlations: some limiting cases.
AB  - Recent advances have shown that the empirical correlation matrices of dynamical
      systems can be modeled as random matrices, for most part, chosen from an
      appropriate ensemble of the random matrix theory (RMT). In this work, we study
      certain limiting cases where this approach could potentially break down. Using a
      combination of analytical and numerical tools, we especially study the eigenvalue
      density and its spacing distribution. We show that the correlation matrices
      obtained from multivariate spatiotemporal timeseries, in a regime of
      spatiotemporal chaos, lead to strong deviations from RMT. We illustrate the
      results with time-series data drawn from coupled map lattices. We also explore
      the transition to the RMT regime from the limiting cases.

PMID- 15244879
TI  - Fcc-bcc transition for Yukawa interactions determined by applied strain
      deformation.
AB  - Calculations of the work required to transform between bcc and fcc phases yield a
      high-precision bcc-fcc transition line for monodisperse point Yukawa (screened
      Coulomb) systems. Our results agree qualitatively but not quantitatively with
      recently published simulations and phenomenological criteria for the bcc-fcc
      transition. In particular, the bcc-fcc-fluid triple point lies at a higher
      inverse screening length than previously reported.

PMID- 15244880
TI  - Thermodynamic properties of He-H2 fluid mixtures over a wide range of
      temperatures and pressures.
AB  - The effect of pressure P and temperature T on the properties of mixing of helium
      hydrogen (He-H2 ) fluid mixture is studied based on statistical mechanical
      perturbation theory. The constituent species are considered to be interacting via
      a pair potential consisting of short range repulsion and a long range attraction
      which has been included through a double Yukawa (DY) potential. He and H2 are the
      lightest elements; therefore, the quantum effect is included via first-order
      quantum correction in the framework of Wigner-Kirkwood expansion. The
      dimerization of the H2 molecule is treated as a hard convex body fluid for which
      the equation of state (EOS) can be derived from hard sphere system based on
      scaled particle theory. An advanced and most recent EOS has been used for our
      investigation. The use of the DY potential, which can readily be simulated to
      empirical potentials, has enabled us to obtain analytical expressions for
      attractive and quantum energy contributions in terms of Laplace transforms. With
      a view to ensure internal consistency of the various thermodynamic functions to
      extract information on segregation and order in the mixture, different functions,
      such as compressibility factor, Gibbs free energy of mixing, entropy of mixing,
      and concentration fluctuations in the long wavelength limit, have been calculated
      as functions of composition of the mixture over an extended region of P and T.
      The results suggest that segregation, heterocoordination, or both may occur in
      the He-H2 mixture depending upon its composition, pressure, and temperature.

PMID- 15244881
TI  - Traffic behavior near an off ramp in the cellular automaton traffic model.
AB  - In this paper, we investigate the off-ramp system on the highway using the
      cellular automaton traffic model. Both the system without an exit lane (case 1)
      and that with an exit lane (case 2) are considered. The phase diagram and its
      variation with L(D) (the length of exit lane in case 2 and the length of a
      special lane-changing section in case 1) is studied. Two phase regions are found
      in case 1 and a new phase, i.e., the maximum flux phase, is reported in case 2.
      The density (velocity) distribution near the off ramp and the influence of L(D)
      on the traffic flow are also discussed in both cases.

PMID- 15244882
TI  - Wave formation by time delays in randomly coupled oscillators.
AB  - We study the dynamics of randomly coupled oscillators when interactions between
      oscillators are time delayed due to the finite and constant speed of coupling
      signals. Numerical simulations show that the time delays, proportional to the
      Euclidean distances between interacting oscillators, can induce near regular
      waves in addition to near in-phase synchronous oscillations even though
      oscillators are randomly coupled. We discuss the stability conditions for the
      wave states and the in-phase synchronous states.

PMID- 15244883
TI  - Common scaling patterns in intertrade times of U. S. stocks.
AB  - We analyze the sequence of time intervals between consecutive stock trades of
      thirty companies representing eight sectors of the U.S. economy over a period of
      4 yrs. For all companies we find that: (i) the probability density function of
      intertrade times may be fit by a Weibull distribution, (ii) when appropriately
      rescaled the probability densities of all companies collapse onto a single curve
      implying a universal functional form, (iii) the intertrade times exhibit power
      law correlated behavior within a trading day and a consistently greater degree of
      correlation over larger time scales, in agreement with the correlation behavior
      of the absolute price returns for the corresponding company, and (iv) the
      magnitude series of intertrade time increments is characterized by long-range
      power-law correlations suggesting the presence of nonlinear features in the
      trading dynamics, while the sign series is anticorrelated at small scales. Our
      results suggest that independent of industry sector, market capitalization and
      average level of trading activity, the series of intertrade times exhibit
      possibly universal scaling patterns, which may relate to a common mechanism
      underlying the trading dynamics of diverse companies. Further, our observation of
      long-range power-law correlations and a parallel with the crossover in the
      scaling of absolute price returns for each individual stock, support the
      hypothesis that the dynamics of transaction times may play a role in the process
      of price formation.

PMID- 15244884
TI  - Small numerators cancelling small denominators of the high-temperature scaling
      variables: a systematic explanation in arbitrary dimensions.
AB  - We describe a method to express the susceptibility and higher derivatives of the
      free energy in terms of the scaling variables (Wegner's nonlinear scaling fields)
      associated with the high-temperature (HT) fixed point of the Dyson hierarchical
      model in arbitrary dimensions. We give a closed form solution of the linearized
      problem. We check that up to order 7 in the HT expansion, all the poles ("small
      denominators") that would naively appear in some positive dimension are canceled
      by zeros ("small numerators"). The requirement of continuity in the dimension can
      be used to lift ambiguities which appear in calculations at fixed dimension. We
      show that the existence of a HT phase in the infinite volume limit for a
      continuous set of values of the dimension, requires that this mechanism works to
      all orders. On the other hand, most poles at negative values of the dimensional
      parameter [where the free energy density is not well-defined, but renormalization
      group (RG) flows can be studied] persist and reflect the fact that for special
      negative values of the dimension, finite-size corrections become leading terms.
      We show that the inverse problem is also free of small denominator problems and
      that the initial values of the scaling variables can be expressed in terms of the
      infinite volume limit of the susceptibility and higher derivatives of the free
      energy. We discuss the existence of an infinite number of conserved quantities
      (RG invariants) and their relevance for the calculation of universal ratios of
      critical amplitudes.

PMID- 15244885
TI  - Scaling of the linear response in simple aging systems without disorder.
AB  - The time-dependent scaling of the thermoremanent and zero-field-cooled
      susceptibilities in ferromagnetic spin systems undergoing aging after a quench to
      a temperature at or below criticality is studied. A recent debate on their
      interpretation is resolved by showing that for systems with a short-ranged
      equilibrium spin-spin correlator and above their roughening temperature, the
      field-cooled susceptibility chi(FC)(t)-chi(0) approximately t(-A), where chi(0)
      is related to the equilibrium magnetization and the exponent A is related to the
      time-dependent scaling of the interface width between ordered domains. The same
      effect also dominates the scaling of the zero-field-cooled susceptibility
      chi(ZFC)(t,s), but does not enter into the thermoremanent susceptibility
      rho(TRM)(t,s). However, there may be large finite-time corrections to the scaling
      of rho(TRM)(t,s) which are explicitly derived and may be needed in order to
      extract reliable aging exponents. Consistency with the predictions of local scale
      invariance is confirmed in the Glauber-Ising and spherical models.

PMID- 15244886
TI  - Vortex velocity probability distributions in phase-ordering kinetics.
AB  - The calculation of the point vortex velocity probability distribution function
      (VVPDF) is extended to a larger class of systems beyond the nonconserved time
      dependent Ginzburg-Landau (TDGL) model treated earlier. The range is extended to
      include certain anisotropic models and the conserved order parameter case. The
      VVPDF still satisfies scaling with large velocity tails as for the nonconserved
      isotropic case. It is shown that the average vortex speed can be self
      consistently expressed in terms of correlation functions associated with a
      Gaussian auxiliary field. In the conserved order parameter case the average
      vortex speed decays as t(-1) compared to the t(-1/2) decay for the nonconserved
      case.

PMID- 15244887
TI  - Entropy and information in neural spike trains: progress on the sampling problem.
AB  - The major problem in information theoretic analysis of neural responses and other
      biological data is the reliable estimation of entropy-like quantities from small
      samples. We apply a recently introduced Bayesian entropy estimator to synthetic
      data inspired by experiments, and to real experimental spike trains. The
      estimator performs admirably even very deep in the undersampled regime, where
      other techniques fail. This opens new possibilities for the information theoretic
      analysis of experiments, and may be of general interest as an example of learning
      from limited data.

PMID- 15244888
TI  - Disorder-induced rounding of the phase transition in the large-q-state Potts
      model.
AB  - The phase transition in the q -state Potts model with homogeneous ferromagnetic
      couplings is strongly first order for large q, while it is rounded in the
      presence of quenched disorder. Here we study this phenomenon on different two
      dimensional lattices by using the fact that the partition function of the model
      is dominated by a single diagram of the high-temperature expansion, which is
      calculated by an efficient combinatorial optimization algorithm. For a given
      finite sample with discrete randomness the free energy is a piecewise linear
      function of the temperature, which is rounded after averaging, however, the
      discontinuity of the internal energy at the transition point (i.e., the latent
      heat) stays finite even in the thermodynamic limit. For a continuous disorder,
      instead, the latent heat vanishes. At the phase transition point the dominant
      diagram percolates and the total magnetic moment is related to the size of the
      percolating cluster. Its fractal dimension is found d(f) = ( 5 + square root of
      5)/4 and it is independent of the type of the lattice and the form of disorder.
      We argue that the critical behavior is exclusively determined by disorder and the
      corresponding fixed point is the isotropic version of the so-called infinite
      randomness fixed point, which is realized in random quantum spin chains. From
      this mapping we conjecture the values of the critical exponents as beta=2- d(f),
      beta(s) =1/2, and nu=1.

PMID- 15244889
TI  - Glassy phase in the Hamiltonian mean-field model.
AB  - We study the relaxation dynamics of a Hamiltonian system of N fully coupled XY
      spins. The thermodynamics of the system predicts a ferromagnetic and a
      paramagnetic phase. Starting from out-of-equilibrium initial conditions, the
      dynamics at constant energy drives the system into quasistationary states (QSSs)
      characterized by dynamical frustration. We introduce the spin polarization as an
      order parameter which allows us to interpret the dynamically generated QSS regime
      as a glassy phase of the model.

PMID- 15244890
TI  - Approach to equilibrium in adiabatically evolving potentials.
AB  - For a potential function (in one dimension) which evolves from a specified
      initial form V(i)(x) to a different V(f)(x) asymptotically, we study the
      evolution, in an overdamped dynamics, of an initial probability density to its
      final equilibrium. There can be unexpected effects that can arise from the time
      dependence. We choose a time variation of the form V(x,t) = V(f)(x) + (V(i) -
      V(f)) e(-lambda t). For a V(f)(x), which is double welled and a V(i)(x) which is
      simple harmonic, we show that, in particular, if the evolution is adiabatic, this
      results in a decrease in the Kramers time characteristic of V(f)(x). Thus the
      time dependence makes diffusion over a barrier more efficient. There can also be
      interesting resonance effects when V(i)(x) and V(f)(x) are two harmonic
      potentials displaced with respect to each other that arise from the coincidence
      of the intrinsic time scale characterizing the potential variation and the
      Kramers time. Both these features are illustrated through representative
      examples.

PMID- 15244891
TI  - Nonlinear dynamics, rectification, and phase locking for particles on symmetrical
      two-dimensional periodic substrates with dc and circular ac drives.
AB  - We investigate the dynamical motion of particles on a two-dimensional symmetric
      periodic substrate in the presence of both a dc drive along a symmetry direction
      of the periodic substrate and an additional circular ac drive. For large enough
      ac drives, the particle orbit encircles one or more potential maxima of the
      periodic substrate. In this case, when an additional increasing dc drive is
      applied in the longitudinal direction, the longitudinal velocity increases in a
      series of discrete steps that are integer multiples of a omega/(2 pi), where a is
      the lattice constant of the substrate. Fractional steps can also occur. These
      integer and fractional steps correspond to distinct stable dynamical orbits. A
      number of these phases also show a rectification in the positive or negative
      transverse direction where a nonzero transverse velocity occurs in the absence of
      a dc transverse drive. We map out the phase diagrams of the regions of
      rectification as a function of ac amplitude, and find a series of tongues. Most
      of the features, including the steps in the longitudinal velocity and the
      transverse rectification, can be captured with a simple toy model and by
      arguments from nonlinear maps. We have also investigated the effects of thermal
      disorder and incommensuration on the rectification phenomena, and find that for
      increasing disorder, the rectification regions are gradually smeared and the
      longitudinal velocity steps are no longer flat but show a linearly increasing
      velocity.

PMID- 15244892
TI  - Biased growth processes and the "rich-get-richer" principle.
AB  - We study a simple stochastic system with a "rich-get-richer" behavior, in which
      there are 2 states, and N particles that are successively assigned to one of the
      states, with a probability p(i) that depends on the states' occupation n(i) as
      p(i) = n(gamma)(i)/ n(gamma)(1) + n(gamma)(2)). We show that there is a phase
      transition as gamma crosses the critical value gamma(c) =1. For gamma<1, in the
      thermodynamic limit the occupations are approximately the same, n(1)
      approximately n(2). For gamma>1, however, a spontaneous symmetry breaking occurs,
      and the system goes to a highly clustered configuration, in which one of the
      states has almost all the particles. These results also hold for any finite
      number of states (not only two). We show that this "rich-get-richer" principle
      governs the growth dynamics in a simple model of gravitational aggregation, and
      we argue that the same is true in all growth processes mediated by long-range
      forces like gravity.

PMID- 15244893
TI  - Stable method for the calculation of partition functions in the
      superconfiguration approach.
AB  - A general method for the calculation of the partition function of a canonical
      ensemble of noninteracting bound electrons is presented. It consists in a doubly
      recursive procedure with respect to the number of electrons and the number of
      orbitals. Contrary to existing approaches, this recursion relation contains no
      alternate summation of positive and negative numbers, which was the main source
      of numerical uncertainties. It is accompanied with a normalization of partition
      function through the determination of a free parameter consistent with the zeroth
      order saddle-point approximation. The recursion relation allows one to calculate
      accurately partition functions for ions with a large number of orbitals, and is
      therefore important for calculations relying on the superconfiguration
      approximation.

PMID- 15244894
TI  - Stochastic resonance in biological nonlinear evolution models.
AB  - We investigate stochastic resonance in the nonlinear, one-dimensional Fisher
      Eigen model (FEM), which represents an archetypal model for biological evolution
      based on a global coupling scheme. In doing so we consider different periodically
      driven fitness functions which govern the evolution of a biological phenotype
      population. For the case of a simple harmonic fitness function we are able to
      derive the exact analytic solution for the asymptotic probability density. A
      distinct feature of this solution is a phase lag between the driving signal and
      the linear response of the system. Furthermore, for more complex systems a
      general perturbation theory (linear response approximation) is put forward. Using
      the latter approach, we investigate stochastic resonance in terms of the spectral
      amplification measure for a quadratic, a quartic single-peaked, and for a
      bistable fitness function. Our analytical results are also compared with those of
      detailed numerical simulations. Our findings vindicate that stochastic resonance
      does occur in these nonlinear, globally coupled biological systems.

PMID- 15244895
TI  - Quantum spherical spin models.
AB  - A recently introduced class of quantum spherical spin models is considered in
      detail. Since the spherical constraint already contains a kinetic part, the
      Hamiltonian need not have kinetic term. As a consequence, situations with or
      without momenta in the Hamiltonian can be described, which may lead to different
      symmetry classes. Two models that show this difference are analyzed. Both models
      are exactly solvable and their phase diagram is analyzed. A transversal external
      field leads to a phase transition line that ends in a quantum critical point. The
      two considered symmetries of the Hamiltonian considered give different critical
      phenomena in the quantum critical region. The model with momenta is argued to be
      analog to the large-N limit of an SU(N) Heisenberg ferromagnet, and the model
      without momenta shares the critical phenomena of an SU(N) Heisenberg
      antiferromagnet.

PMID- 15244896
TI  - Dynamics of the adaptive natural gradient descent method for soft committee
      machines.
AB  - Adaptive natural gradient descent (ANGD) method realizes natural gradient descent
      (NGD) without needing to know the input distribution of learning data and reduces
      the calculation cost from a cubic order to a square order. However, no
      performance analysis of ANGD has been done. We have developed a statistical
      mechanical theory of the simplified version of ANGD dynamics for soft committee
      machines in on-line learning; this method provides deterministic learning
      dynamics expressed through a few order parameters, even though ANGD intrinsically
      holds a large approximated Fisher information matrix. Numerical results obtained
      using this theory were consistent with those of a simulation, with respect not
      only to the learning curve but also to the learning failure. Utilizing this
      method, we numerically evaluated ANGD efficiency and found that ANGD generally
      performs as well as NGD. We also revealed the key condition affecting the
      learning plateau in ANGD.

PMID- 15244897
TI  - Extended heat-fluctuation theorems for a system with deterministic and stochastic
      forces.
AB  - Heat fluctuations over a time tau in a nonequilibrium stationary state and in a
      transient state are studied for a simple system with deterministic and stochastic
      components: a Brownian particle dragged through a fluid by a harmonic potential
      which is moved with constant velocity. Using a Langevin equation, we find the
      exact Fourier transform of the distribution of these fluctuations for all tau. By
      a saddle-point method we obtain analytical results for the inverse Fourier
      transform, which, for not too small tau, agree very well with numerical results
      from a sampling method as well as from the fast Fourier transform algorithm. Due
      to the interaction of the deterministic part of the motion of the particle in the
      mechanical potential with the stochastic part of the motion caused by the fluid,
      the conventional heat fluctuation theorem is, for infinite and for finite tau,
      replaced by an extended fluctuation theorem that differs noticeably and
      measurably from it. In particular, for large fluctuations, the ratio of the
      probability for absorption of heat (by the particle from the fluid) to the
      probability to supply heat (by the particle to the fluid) is much larger here
      than in the conventional fluctuation theorem.

PMID- 15244898
TI  - Transient characteristics of chaos synchronization in a semiconductor laser
      subject to optical feedback.
AB  - We have investigated the transient characteristics of two types of chaos
      synchronization in a semiconductor laser subject to optical feedback: complete
      synchronization and strong injection locking-type synchronization. We have
      calculated the statistical distribution of the transient response time of
      synchronization when the initial position in the starting attractor is varied.
      For complete synchronization, the distribution of the transient response time has
      much larger average and variance than the average period of the chaotic
      oscillations. Conversely, a short transient response time is obtained for strong
      injection locking-type synchronization. We found that the transient response time
      is dependent upon the maximum Lyapunov exponent of the chaotic temporal waveform
      for complete synchronization, whereas it is almost constant for strong injection
      locking-type synchronization.

PMID- 15244899
TI  - Spatiotemporal chaos control with a target wave in the complex Ginzburg-Landau
      equation system.
AB  - An effective method for controlling spiral turbulence in spatially extended
      systems is realized by introducing a spatially localized inhomogeneity into a two
      dimensional system described by the complex Ginzburg-Landau equation. Our
      numerical simulations show that with the introduction of the inhomogeneity, a
      target wave can be produced, which will sweep all spiral defects out of the
      boundary of the system. The effects exist in certain parameter regions where the
      spiral waves are absolutely unstable. A theoretical explanation is given to
      reveal the underlying mechanism.

PMID- 15244900
TI  - Chemical waves with line defects in the Belousov-Zhabotinsky reaction.
AB  - We report our experimental observations of line-defected chemical waves in a
      quasi-two-dimensional reaction-diffusion system of Belousov-Zhabotinsky reaction.
      The observed line defects are explicit, which can be directly monitored in real
      time. In the parameter space, the state of the chemical waves with line defects
      is located between two regimes of the defect-mediated turbulence. The line
      defects appear in target waves as well as in spiral waves. We demonstrate that
      the line defects come out in traveling waves as the later reorganize their
      spatial topologies to adapt to the change in the local dynamics from simple to
      complex oscillations or vice versa.

PMID- 15244901
TI  - Macroscopic detection of the strong stochasticity threshold in Fermi-Pasta-Ulam
      chains of oscillators.
AB  - The largest Lyapunov exponent of a system composed by a heavy impurity embedded
      in a chain of anharmonic nearest-neighbor Fermi-Pasta-Ulam oscillators is
      numerically computed for various values of the impurity mass M. A crossover
      between weak and strong chaos is obtained at the same value epsilon(T) of the
      energy density epsilon (energy per degree of freedom) for all the considered
      values of the impurity mass M. The threshold epsilon(T) coincides with the value
      of the energy density epsilon at which a change of scaling of the relaxation time
      of the momentum autocorrelation function of the impurity occurs and that was
      obtained in a previous work [Phys. Rev. E 65, 036228 (2002)]]. The complete
      Lyapunov spectrum does not depend significantly on the impurity mass M. These
      results suggest that the impurity does not contribute significantly to the
      dynamical instability (chaos) of the chain and can be considered as a probe for
      the dynamics of the system to which the impurity is coupled. Finally, it is shown
      that the Kolmogorov-Sinai entropy of the chain has a crossover from weak to
      strong chaos at the same value of the energy density as the crossover value
      epsilon(T) of largest Lyapunov exponent. Implications of this result are
      discussed.

PMID- 15244902
TI  - Experimental simulation of quantum graphs by microwave networks.
AB  - We present the results of experimental and theoretical study of irregular,
      tetrahedral microwave networks consisting of coaxial cables (annular waveguides)
      connected by T joints. The spectra of the networks were measured in the frequency
      range 0.0001-16 GHz in order to obtain their statistical properties such as the
      integrated nearest neighbor spacing distribution and the spectral rigidity
      Delta(3) (L). The comparison of our experimental and theoretical results shows
      that microwave networks can simulate quantum graphs with time reversal symmetry.
      In particular, we use the spectra of the microwave networks to study the periodic
      orbits of the simulated quantum graphs. We also present experimental study of
      directional microwave networks consisting of coaxial cables and Faraday isolators
      for which the time reversal symmetry is broken. In this case our experimental
      results indicate that spectral statistics of directional microwave networks
      deviate from predictions of Gaussian orthogonal ensembles in random matrix theory
      approaching, especially for small eigenfrequency spacing s, results for Gaussian
      unitary ensembles. Experimental results are supported by the theoretical analysis
      of directional graphs.

PMID- 15244903
TI  - Topological aspects of the structure of chaotic attractors in R3.
AB  - Strange attractors with Lyapunov dimension d(L) <3 can be classified by branched
      manifolds. They can also be classified by the bounding tori that enclose them.
      Bounding tori organize branched manifolds (classes of strange attractors) in the
      same way as the branched manifolds organize the periodic orbits in a strange
      attractor. We describe how bounding tori are constructed and expressed in a
      useful canonical form. We present the properties of these canonical forms and
      show that they can be uniquely coded by analogs of periodic orbits of period g-1,
      where g is the genus. We describe the structure of the global Poincare surface of
      section for an attractor enclosed by a genus- g torus and determine the
      transition matrix for flows between the g-1 components of the Poincare surface of
      section. Finally, we show how information about a bounding torus can be extracted
      from scalar time series.

PMID- 15244904
TI  - Design and robustness of delayed feedback controllers for discrete systems.
AB  - We study a matrix form of time-delay feedback control in the context of discrete
      time maps of high dimension. In almost all cases where standard proportional
      feedback control methods can achieve control, time-delay feedback controllers
      containing only static elements can be designed to achieve identical linear
      stability properties. Analysis of an example involving a ring of coupled maps
      that can be controlled at only two sites demonstrates that the time-delay
      controller equivalent to a standard optimal controller can be equally robust in
      the presence of noise, except at special points in parameter space where the
      uncontrolled system has a mode with Floquet multiplier exactly equal to 1.
      Numerical simulations confirm the results of the analysis.

PMID- 15244905
TI  - Testing time symmetry in time series using data compression dictionaries.
AB  - Time symmetry, often called statistical time reversibility, in a dynamical
      process means that any segment of time-series output has the same probability of
      occurrence in the process as its time reversal. A technique, based on symbolic
      dynamics, is proposed to distinguish such symmetrical processes from asymmetrical
      ones, given a time-series observation of the otherwise unknown process. Because
      linear stochastic Gaussian processes, and static nonlinear transformations of
      them, are statistically reversible, but nonlinear dynamics such as dissipative
      chaos are usually statistically irreversible, a test will separate large classes
      of hypotheses for the data. A general-purpose and robust statistical test
      procedure requires adapting to arbitrary dynamics which may have significant time
      correlation of undetermined form. Given a symbolization of the observed time
      series, the technology behind adaptive dictionary data compression algorithms
      offers a suitable estimate of reversibility, as well as a statistical likelihood
      test. The data compression methods create approximately independent segments
      permitting a simple and direct null test without resampling or surrogate data. We
      demonstrate the results on various time-series-reversible and irreversible
      systems.

PMID- 15244906
TI  - Domain of attraction for stabilized orbits in time delayed feedback controlled
      Duffing systems.
AB  - Time delayed feedback control is well known as a practical method for stabilizing
      unstable periodic orbits embedded in chaotic attractors. However, this control
      method still has an open problem of estimating domain of attraction for target
      unstable periodic orbits. In this paper, we numerically discuss the domain of
      attraction in Duffing systems under the control method. The disturbance to
      initial conditions reveals that the domain of attraction possibly exhibits self
      similar structures in its boundaries.

PMID- 15244907
TI  - Resonant patterns in noisy active media.
AB  - We investigate noise-controlled resonant response of active media to weak
      periodic forcing, both in excitable and oscillatory regimes. In the excitable
      regime, we find that noise-induced irregular wave structures can be reorganized
      into frequency-locked resonant patterns by weak signals with suitable
      frequencies. The resonance occurs due to a matching condition between the signal
      frequency and the noise-induced inherent time scale of the media. m:1 resonant
      regions similar to the Arnold tongues in frequency locking of self-sustained
      oscillatory media are observed. In the self-sustained oscillatory regime, noise
      also controls the oscillation frequency and reshapes significantly the Arnold
      tongues. The combination of noise and weak signal thus could provide an efficient
      tool to manipulate active extended systems in experiments.

PMID- 15244908
TI  - Spectral properties and classical decays in quantum open systems.
AB  - We study the relationship between the spectral properties of diffusive open
      quantum maps and the classical spectrum of Ruelle-Pollicott resonances. The
      leading resonances determine the asymptotic time regime for several quantities of
      interest--the linear entropy, the Loschmidt echo, and the correlations of the
      initial state. A numerical method that allows an efficient calculation of the
      leading spectrum is developed using a truncated basis adapted to the dynamics.

PMID- 15244909
TI  - Maturation of crack patterns.
AB  - Superficial (two-dimensional) crack patterns appear when a thin layer of material
      elastically attached to a substrate contracts. We study numerically the
      maturation process undergone by these crack patterns when they are allowed to
      adapt in order to reduce its energy. The process models the evolution in depth of
      cracks in geological formations and in starch samples ("columnar jointing"), and
      also the time evolution (over thousands of years) of crack patterns in frozen
      soils. We observe an evolution towards a polygonal pattern that consists of a
      fixed distribution of polygons with mainly five, six, and seven sides. They
      compare very well with known experimental examples. The evolution of one of these
      "mature" patterns upon reduction of the degree of contraction is also considered.
      We find that the pattern adapts by closing some of the cracks and rearranging
      those in the immediate neighborhood. This produces a change of the mean size of
      the polygons, but remarkably no changes of the statistical properties of the
      pattern. Comparison with the same behavior recently observed in starch samples is
      presented.

PMID- 15244910
TI  - Control of Hamiltonian chaos as a possible tool to control anomalous transport in
      fusion plasmas.
AB  - It is shown that a relevant control of Hamiltonian chaos is possible through
      suitable small perturbations whose form can be explicitly computed. In
      particular, it is possible to control (reduce) the chaotic diffusion in the phase
      space of a Hamiltonian system with 1.5 degrees of freedom which models the
      diffusion of charged test particles in a turbulent electric field across the
      confining magnetic field in controlled thermonuclear fusion devices. Though still
      far from practical applications, this result suggests that some strategy to
      control turbulent transport in magnetized plasmas, in particular, tokamaks, is
      conceivable. The robustness of the control is investigated in terms of a
      departure from the optimum magnitude, of a varying cutoff at large wave vectors,
      and of random errors on the phases of the modes. In all three cases, there is a
      significant region of maximum efficiency in the vicinity of the optimum control
      term.

PMID- 15244911
TI  - Random Boolean network model exhibiting deterministic chaos.
AB  - This paper considers a simple Boolean network with N nodes, each node's state at
      time t being determined by a certain number of parent nodes, which may vary from
      one node to another. This is an extension of a model studied by Andrecut and Ali
      [Int. J. Mod. Phys. B 15, 17 (2001)]], who consider the same number of parents
      for all nodes. We make use of the same Boolean rule as Andrecut and Ali, provide
      a generalization of the formula for the probability of finding a node in state 1
      at a time t, and use simulation methods to generate consecutive states of the
      network for both the real system and the model. The results match well. We study
      the dynamics of the model through sensitivity of the orbits to initial values,
      bifurcation diagrams, and fixed point analysis. We show that the route to chaos
      is due to a cascade of period-doubling bifurcations which turn into reversed
      (period-halving) bifurcations for certain combinations of parameter values.

PMID- 15244912
TI  - Embeddings of a strange attractor into R3.
AB  - The algorithm for determining a global Poincare section is applied to a
      previously studied dynamical system on R2 x S1 and a one-parameter family of
      embeddings of the strange attractor it generates into R3. We find that the
      topological properties of the attractor are embedding dependent to a limited
      extent. These embeddings rigidly preserve mechanism, which is a simple stretch
      and fold. The embeddings studied show three discrete topological degrees of
      freedom: parity, global torsion, and braid type of the genus-one torus bounding
      the embedded attractor.

PMID- 15244913
TI  - Encircling an exceptional point.
AB  - We calculate analytically the geometric phases that the eigenvectors of a
      parametric dissipative two-state system described by a complex symmetric
      Hamiltonian pick up when an exceptional point (EP) is encircled. An EP is a
      parameter setting where the two eigenvalues and the corresponding eigenvectors of
      the Hamiltonian coalesce. We show that it can be encircled on a path along which
      the eigenvectors remain approximately real and discuss a microwave cavity
      experiment, where such an encircling of an EP was realized. Since the wave
      functions remain approximately real, they could be reconstructed from the nodal
      lines of the recorded spatial intensity distributions of the electric fields
      inside the resonator. We measured the geometric phases that occur when an EP is
      encircled four times and thus confirmed that for our system an EP is a branch
      point of fourth order.

PMID- 15244915
TI  - Amplification of noise in a cascade chemical reaction.
AB  - Networks of chemical reactions have been given much attention recently. However,
      dynamical aspects of such networks remain to be elucidated. In this paper, we
      study a cascade chemical reaction, consisting of a series of downstream-coupled
      Brusselators. Along the cascade of reaction, small fluctuations naturally
      existing in the concentration of chemical species are amplified. Such
      amplification of small noise leads to the formation of chemical oscillations in
      the downstream chemical species. The amplification rate of small noise in the
      concentration along the cascade is studied and the method to calculate the
      amplification rate analytically is developed. It is also shown that the nonlinear
      evolution of the chemical oscillation in the downstream reaction strongly depends
      on the frequency of the initial inlet chemical concentration.

PMID- 15244914
TI  - Phase-locked patterns and amplitude death in a ring of delay-coupled limit cycle
      oscillators.
AB  - We study the existence and stability of phase-locked patterns and amplitude death
      states in a closed chain of delay coupled identical limit cycle oscillators that
      are near a supercritical Hopf bifurcation. The coupling is limited to nearest
      neighbors and is linear. We analyze a model set of discrete dynamical equations
      using the method of plane waves. The resultant dispersion relation, which is
      valid for any arbitrary number of oscillators, displays important differences
      from similar relations obtained from continuum models. We discuss the general
      characteristics of the equilibrium states including their dependencies on various
      system parameters. We next carry out a detailed linear stability investigation of
      these states in order to delineate their actual existence regions and to
      determine their parametric dependence on time delay. Time delay is found to
      expand the range of possible phase-locked patterns and to contribute favorably
      toward their stability. The amplitude death state is studied in the parameter
      space of time delay and coupling strength. It is shown that death island regions
      can exist for any number of oscillators N in the presence of finite time delay. A
      particularly interesting result is that the size of an island is independent of N
      when N is even but is a decreasing function of N when N is odd.

PMID- 15244916
TI  - Universal spectral statistics in Wigner-Dyson, chiral, and Andreev star graphs.
      I. Construction and numerical results.
AB  - In a series of two papers we investigate the universal spectral statistics of
      chaotic quantum systems in the ten known symmetry classes of quantum mechanics.
      In this first paper we focus on the construction of appropriate ensembles of star
      graphs in the ten symmetry classes. A generalization of the Bohigas-Giannoni
      Schmit conjecture is given that covers all these symmetry classes. The conjecture
      is supported by numerical results that demonstrate the fidelity of the spectral
      statistics of star graphs to the corresponding Gaussian random-matrix theories.

PMID- 15244917
TI  - Universal spectral statistics in Wigner-Dyson, chiral, and Andreev star graphs.
      II. Semiclassical approach.
AB  - A semiclassical approach to the universal ergodic spectral statistics in quantum
      star graphs is presented for all known ten symmetry classes of quantum systems.
      The approach is based on periodic orbit theory, the exact semiclassical trace
      formula for star graphs, and on diagrammatic techniques. The appropriate spectral
      form factors are calculated up to one order beyond the diagonal and self-dual
      approximations. The results are in accordance with the corresponding random
      matrix theories which supports a properly generalized Bohigas-Giannoni-Schmit
      conjecture.

PMID- 15244918
TI  - Dynamics of two mutually coupled semiconductor lasers: instantaneous coupling
      limit.
AB  - We consider two semiconductor lasers coupled face to face under the assumption
      that the delay time of the injection is small. The model under consideration
      consists of two coupled rate equations, which approximate the coupled Lang
      Kobayashi system as the delay becomes small. We perform a detailed study of the
      synchronized and antisynchronized solutions for the case of identical systems and
      compare results from two models: with the delay and with instantaneous coupling.
      The bifurcation analysis of systems with detuning reveals that self-pulsations
      appear via bifurcations of stationary (i.e., continuous wave) solutions. We
      discover the connection between stationary solutions in systems with detuning and
      synchronous (also antisynchronous) solutions of coupled identical systems. We
      also identify a codimension 2 bifurcation point as an organizing center for the
      emergence of chaotic behavior.

PMID- 15244919
TI  - Universal instabilities of radio-frequency traps.
AB  - Using standard tools of nonlinear dynamics we analyze recently discovered
      instabilities of radio-frequency charged-particle traps. In the cw-driven
      cylindrical Kingdon trap the instabilities occur at the two values eta*(3)
      =3.6130467...and eta*(4) =4.4311244...of the trap's control parameter eta.
      Analytical estimates based on the theory of Mathieu functions predict eta*(3) =pi
      square root of [(363-32 pi(2))/(66 pi square root of (6-48
      pi(2))]=3.6923922...and eta*(4) = [(square root of pi)/2) x [(363-32
      pi(2))/(square root of (1089+48 pi(2))-12 pi)](1/2) =4.4965466... The kicked
      Kingdon trap, an analytically solvable model, predicts eta*(3) = 1/3 square root
      of 105=3.4156502...and eta*(4) = square root of 17=4.1231056... We show that
      similar instabilities occur in the two-particle Paul trap and the cw-driven
      spherical Kingdon trap.

PMID- 15244920
TI  - Attraction of spiral waves by localized inhomogeneities with small-world
      connections in excitable media.
AB  - Trapping and untrapping of spiral tips in a two-dimensional homogeneous excitable
      medium with local small-world connections are studied by numerical simulation. In
      a homogeneous medium which can be simulated with a lattice of regular
      neighborhood connections, the spiral wave is in the meandering regime. When
      changing the topology of a small region from regular connections to small-world
      connections, the tip of the spiral waves is attracted by the small-world region,
      where the average path length declines with the introduction of long distant
      connections. The "trapped" phenomenon also occurs in regular lattices where the
      diffusion coefficient of the small region is increased. The above results can be
      explained by the eikonal equation, the Luther equation, and the relation between
      the core radius and the diffusion coefficient.

PMID- 15244921
TI  - Phase-dependent output of scattering process for traveling breathers.
AB  - Scattering process between one-dimensional traveling breathers (TBs), i.e.,
      oscillatory traveling pulses, for the complex Ginzburg-Landau equation (CGLE)
      with external forcing and a three-component activator-substrate-inhibitor model
      are studied. The input-output relation depends in general on the phase of two TBs
      at collision point, which makes a contrast to the case for the steady traveling
      pulses. A hidden unstable solution called the scattor plays a crucial role to
      understand the scattering dynamics. Stable and unstable manifolds of the scattor
      direct the traffic flows of the scattering process. A transition point of the
      input-output relation in a parameter space such as from preservation to
      annihilation corresponds to when the orbit crosses the stable manifold of the
      scattor. The phase dependency of input-output relation comes from the fact that
      the profiles at collision point make a loop parametrized by the phase and it
      traverses the stable manifold of the scattor. A global bifurcation viewpoint is
      quite useful not only to understand how TBs emerge but also to detect scattors.
      It turns out that the scattor for the CGLE (respectively the three-component
      system) becomes an unstable time-periodic (respectively stationary) solution.

PMID- 15244922
TI  - Noise-induced coherence in bistable systems with multiple time delays.
AB  - We study the correlation properties of noise-driven bistable systems with
      multiple time-delay feedbacks. For small noisy perturbation and feedback
      magnitude, we derive the autocorrelation function and the power spectrum based on
      the two-state model with transition rates depending on the earlier states of the
      system. A comparison between the single and double time delays reveals that the
      auto correlation functions exhibit exponential decay with small undulation for
      the double time delays, in contrast with the remarkable oscillatory behavior at
      small time lags for the single time delay.

PMID- 15244923
TI  - Effect of parameter mismatch on the synchronization of chaotic semiconductor
      lasers with electro-optical feedback.
AB  - We investigate the detrimental effects of parameter mismatch on the
      synchronization of semiconductor lasers with electro-optical feedback, whose
      intensity dynamics can display a hyperchaotic behavior. Analytical techniques are
      developed to study the statistical properties of the synchronization error as a
      function of the various types of mismatches. The multiple mismatch case, which is
      of high experimental interest, is also studied and some compensation conditions
      allowing the improvement of the synchronization are derived. The analytical
      predictions are confirmed by numerical simulations and by some experimental
      measurements.

PMID- 15244924
TI  - Classical, semiclassical, and quantum investigations of the four-sphere
      scattering system.
AB  - A genuinely three-dimensional system, viz. the hyperbolic four-sphere scattering
      system, is investigated with classical, semiclassical, and quantum mechanical
      methods at various center-to-center separations of the spheres. The efficiency
      and scaling properties of the computations are discussed by comparisons to the
      two-dimensional three-disk system. While in systems with few degrees of freedom
      modern quantum calculations are, in general, numerically more efficient than
      semiclassical methods, this situation can be reversed with increasing dimension
      of the problem. For the four-sphere system with large separations between the
      spheres, we demonstrate the superiority of semiclassical versus quantum
      calculations, i.e., semiclassical resonances can easily be obtained even in
      energy regions which are unattainable with the currently available quantum
      techniques. The four-sphere system with touching spheres is a challenging problem
      for both quantum and semiclassical techniques. Here, semiclassical resonances are
      obtained via harmonic inversion of a cross-correlated periodic orbit signal.

PMID- 15244925
TI  - Irrational phase synchronization.
AB  - We study the occurrence of physically observable phase locked states between
      chaotic oscillators and rotors in which the frequencies of the coupled systems
      are irrationally related. For two chaotic oscillators, the phenomenon occurs as a
      result of a coupling term which breaks the 2 pi invariance in the phase
      equations. In the case of rotors, a coupling term in the angular velocities
      results in very long times during which the coupled systems exhibit alternatively
      irrational phase synchronization and random phase diffusion. The range of
      parameters for which the phenomenon occurs contains an open set, and is thus
      physically observable.

PMID- 15244926
TI  - Traveling waves in rotating Rayleigh-Benard convection.
AB  - A combined analytical, numerical, and experimental study of the traveling-wave
      wall mode in rotating Rayleigh-Benard convection is presented. No-slip top and
      bottom boundary conditions are used for the numerical computation of the linear
      stability, and the coefficients of the linear complex Ginzburg-Landau equation
      are then computed for various rotation rates. Numerical results for the no-slip
      boundary conditions are compared with free-slip calculations and with
      experimental data, and detailed comparison is made at a dimensionless rotation
      rate Omega=274. It is found that the inclusion of the more realistic no-slip
      boundary conditions for the top and bottom surfaces brings the numerical linear
      stability analysis into better agreement with the experimental data compared with
      results using free-slip top/bottom boundary conditions. Some remaining
      discrepancies may be accounted for by the finite conductivity of the sidewall
      boundaries.

PMID- 15244927
TI  - Probability density functions of decaying passive scalars in periodic domains: an
      application of Sinai-Yakhot theory.
AB  - Employing the formalism introduced by Phys. Rev. Lett. 63, 1962 (1989)], we study
      the probability density functions (pdf's) of decaying passive scalars in periodic
      domains under the influence of smooth large scale velocity fields. The particular
      regime we focus on is one where the normalized scalar pdf's attain a self-similar
      profile in finite time, i.e., the so-called strange or statistical eigenmode
      regime. In accordance with the work of Sinai and Yakhot, the central regions of
      the pdf's are power laws. However, the details of the pdf profiles are dependent
      on the physical parameters in the problem. Interestingly, for small Peclet
      numbers the pdf's resemble stretched or pure exponential functions, whereas in
      the limit of large Peclet numbers, there emerges a universal Gaussian form for
      the pdf. Numerical simulations are used to verify these predictions.

PMID- 15244928
TI  - Self-similar scaling in decaying numerical turbulence.
AB  - Decaying turbulence is studied numerically using as initial condition a random
      flow whose shell-integrated energy spectrum increases with wave number k like
      k(q). Alternatively, initial conditions are generated from a driven turbulence
      simulation by simply stopping the driving. It is known that the dependence of the
      decaying energy spectrum on wave number, time, and viscosity can be collapsed
      onto a unique scaling function that depends only on two parameters. This is
      confirmed using three-dimensional simulations and the dependence of the scaling
      function on its two arguments is determined.

PMID- 15244929
TI  - Micromanipulation of sonoluminescing bubbles.
AB  - Micromanipulation of sonoluminescing bubbles is achieved by generating a complex
      sound field consisting of spatially distributed modes of higher harmonics of a
      basic driving frequency. Bubbles can be manipulated in space and shifted to any
      desired spot. The interaction with the complex sound field also allows for
      specification of the violence of a bubble collapse.

PMID- 15244930
TI  - Dependence of turbulent Rayleigh-Taylor instability on initial perturbations.
AB  - The dependency of the self-similar Rayleigh-Taylor bubble acceleration constant
      alpha(b)(identical with [(amplitude)/2] x (displacement) x (Atwood number)) on
      the initial perturbation amplitude h(0k) is described with a model in which the
      exponential growth of a small amplitude packet of modes makes a continuous
      nonlinear transition to its "terminal" bubble velocity proportional, variant
      Fr[equal to(Froude number)(1/2)]. Then, by applying self-similarity (diameter
      proportional, variant amplitude), alpha(b) is found to increase proportional to
      Fr and logarithmically with h(0k). The model has two free parameters that are
      determined from experiments and simulations. The augmentation of long wavelength
      perturbations by mode coupling is also evaluated. This is found to decrease the
      sensitivity of alpha(b) on the initial perturbations when they are smaller than
      the saturation amplitude of the most unstable modes. These results show that
      alpha(b) can vary by a factor of 2-3 with initial conditions in reasonable
      agreement with experiments and simulations.

PMID- 15244931
TI  - Coherent structures in boundary layers of Rayleigh-Benard convection.
AB  - A coherent structure is revealed experimentally by a dyeing technique in the
      boundary layer of Rayleigh-Benard convection in water. Dye accumulates in streaks
      aligned with the mean flow. Possible mechanisms for the formation of these
      streaks are discussed.

PMID- 15244932
TI  - Generation of streamwise vortices in square sudden-expansion flows.
AB  - The intent of the present work is to investigate the nature of jet spreading and
      the process of evolution of the associated embedded streamwise vortices for the
      steady flow through a two-step square sudden expansion. Simulations are performed
      to review the flow physics within a square channel which undergoes a first
      expansion with an uniform step height 0.75h ( h being the inlet channel width);
      and at a streamwise distance 8h from the plane of first expansion the channel
      goes through another expansion with the second step height being half of the
      first step height. Unlike asymmetric jets, the square jet is observed to
      experience relatively faster nonuniform azimuthal perturbations during its
      streamwise evolution and at some downstream location the jet expands in such a
      way that it looks as if it has locally rotated by 45 degrees. The developed four
      pairs of outflow type streamwise vortices (with each pair occupying their
      position at the end of a jet diagonal), which dominated over the first expansion
      zone, seems to control the azimuthal jet deformation process through their
      induced outward velocity. Another important aspect of the present investigation
      is that here we have established a unique pressure analysis which efficiently
      predicts the presence of all the streamwise vortices in the setup and also their
      nature of dynamics without any ambiguity. Moreover, the presented pressure
      analysis suggests that nonuniform lateral flow acceleration within the channel,
      as induced by the developed transverse pressure gradient skewing, influences the
      generation of the streamwise vortices. The pressure analysis also successfully
      predicts every local change in the dynamics of the embedded streamwise vortices,
      during the downstream evolution of the jet.

PMID- 15244933
TI  - Turbulent transition of thermocapillary flow induced by water evaporation.
AB  - Water has been examined for thermocapillary convection while maintained just
      outside the mouth of a stainless-steel, conical funnel where it evaporated at
      different but steady rates. Evaporation at a series of controlled rates was
      produced by reducing the pressure in the vapor-phase to different but constant
      values while maintaining the temperature of the water a few millimeters below the
      interface at 3.56+/-0.03 degrees C in each case. Since water has its maximum
      density at 4 degrees C, these conditions ensured there would be no buoyancy
      driven convection. The measured temperature profile along the liquid-vapor
      interface was found to be approximately axisymmetric and parabolic with its
      minimum on the center line and maximum at the periphery. The thermocapillary flow
      rate was determined in two ways: (1) It was calculated from the interfacial
      temperature gradient measured along the interface. (2) The deflection of a 12.7
      microm-diameter, cantilevered probe inserted into the flow was measured and the
      liquid velocity required to give that deflection determined. The values
      determined by the two methods agree reasonably. As the vapor-phase pressure was
      reduced, the thermocapillary flow rate increased until a limiting value was
      reached. When the pressure was reduced further, certain of the variable relations
      underwent a bifurcation and the power spectrum of the probe displacement
      indicated it was a periodic function with frequency locking. These results
      suggest that thermocapillary flow plays an important role in the energy transport
      near the interface of evaporating water. In particular, it appears that the
      subinterface, uniform-temperature layer, reported in earlier studies, results
      from the mixing produced by the thermocapillary flow. The Stefan boundary
      condition is often applied to determine the energy flux to an interface where
      phase change is occurring; however, when there is strong convective flow parallel
      to the interface, the normal Stefan condition does not give an adequate
      description of the energy transport.

PMID- 15244935
TI  - Falling films and the Marangoni effect.
AB  - The instability of a falling liquid film of an aqueous surfactant solution along
      a vertical slope with surfactant adsorption-desorption at its open surface
      originating surface stresses (Marangoni effect) is investigated. The diffusion of
      surfactant to the film surface from the bulk and desorption of surfactant to the
      gas phase are taken into account. The Navier-Stokes and Fick equations are
      reduced to a system of simpler hence, analytically and numerically, more
      tractable nonlinear evolution equations albeit with nine dimensionless
      parameters. The linear stability analysis yields a dispersion equation that is
      numerically solved and eigenvalues are obtained for various values of significant
      dimensionless parameters. A very rich picture of instabilities appears. In
      addition to the earlier known (Kapitza) hydrodynamic mode there are up to four
      new (Marangoni-driven) diffusion modes. Two modes travel with the liquid velocity
      on the film surface and the other two travel on their own downstream and
      upstream, respectively. One diffusion mode could be identified, in the reference
      frame moving with the liquid on the film surface, as a monotonic instability mode
      hence leading to a patterned film surface. All other modes are oscillatory ones.
      Resonance of modes is also predicted for suitable combinations of the parameters
      of the problem. The mode observed depends upon the surface stress (in terms of a
      dimensionless Marangoni number), the particular choice of the adsorption
      desorption kinetics, and the surface tension state equation at the open surface
      of the film.

PMID- 15244934
TI  - Spiral vortices and Taylor vortices in the annulus between rotating cylinders and
      the effect of an axial flow.
AB  - We present numerical simulations of vortices that appear via primary bifurcations
      out of the unstructured circular Couette flow in the Taylor-Couette system with
      counter rotating as well as with corotating cylinders. The full, time dependent
      Navier Stokes equations are solved with a combination of a finite difference and
      a Galerkin method for a fixed axial periodicity length of the vortex patterns and
      for a finite system of aspect ratio 12 with rigid nonrotating ends in a setup
      with radius ratio eta=0.5. Differences in structure, dynamics, symmetry
      properties, bifurcation, and stability behavior between spiral vortices with
      azimuthal wave numbers M=+/-1 and M=0 Taylor vortices are elucidated and compared
      in quantitative detail. Simulations in axially periodic systems and in finite
      systems with stationary rigid ends are compared with experimental spiral data. In
      a second part of the paper we determine how the above listed properties of the M=
      1, 0, and 1 vortex structures are changed by an externally imposed axial through
      flow with Reynolds numbers in the range -40< or =Re< or =40. Among other things
      we investigate when left handed or right handed spirals or toroidally closed
      vortices are preferred.

PMID- 15244936
TI  - Comparison between theoretical predictions and direct numerical simulation
      results for a decaying turbulent suspension.
AB  - A recently developed theoretical model for a turbulently flowing suspension has
      been applied to a homogeneous, isotropic, and decaying turbulent suspension. The
      predictions are compared with results from direct numerical simulations. The
      agreement is reasonable. Special attention is paid to a physical explanation of
      the influence of the particles on the turbulence of the carrier fluid.

PMID- 15244937
TI  - Breakup of a fluid thread in a confined geometry: droplet-plug transition,
      perturbation sensitivity, and kinetic stabilization with confinement.
AB  - We investigate the influence of geometrical confinement on the breakup of long
      fluid threads in the absence of imposed flow using a lattice Boltzmann model. Our
      simulations primarily focus on the case of threads centered coaxially in a tube
      filled with another Newtonian fluid and subjected to both impulsive and random
      perturbations. We observe a significant slowing down of the rate of thread
      breakup ("kinetic stabilization") over a wide range of the confinement, Lambda=
      R(tube)/R(thread) < or =10 and find that the relative surface energies of the
      liquid components influence this effect. For Lambda<2.3, there is a transition in
      the late-stage morphology between spherical droplets and tube "plugs." Unstable
      distorted droplets ("capsules") form as transient structures for intermediate
      confinement (Lambda approximately equal 2.1-2.5). Surprisingly, the thread
      breakup process for more confined threads (Lambda< or =1.9 ) is found to be
      sensitive to the nature of the initial thread perturbation. Localized impulsive
      perturbations ("taps") cause a "bulging" of the fluid at the wall, followed by
      thread breakup through the propagation of a wave-like disturbance ("end-pinch
      instability") initiating from the thread rupture point. Random impulses along the
      thread, modeling thermal fluctuations, lead to a complex breakup process
      involving a competition between the Raleigh and end-pinch instabilities. We also
      briefly compare our tube simulations to threads confined between parallel plates
      and to multiple interacting threads under confinement.

PMID- 15244938
TI  - Initial-value-problem solution for isolated rippled shock fronts in arbitrary
      fluid media.
AB  - Following the work of Roberts [Los Alamos Scientific Laboratory Report No. LA
      299, 1945 (unpublished)], we investigate the effect of small two-dimensional
      perturbations on an isolated, planar shock front moving steadily through an
      inviscid fluid medium with an arbitrary equation of state (EOS). In the context
      of an initial-value problem, we derive explicit analytical expressions for the
      linearized, time-dependent Fourier coefficients associated with an initial
      corrugation of the front. The temporal evolution of these coefficients
      superficially resembles the attenuated "ringing" of a damped harmonic oscillator,
      but with the important distinctions that the frequency of oscillation is not
      constant, and that the damping factor is not simply an exponential function of
      time t. It is shown that at least two three-parameter families of stable
      solutions exist, one more strongly damped than the other. In both cases, we find
      that the envelope of oscillations decays asymptotically as t(-3/2), with shorter
      wavelengths dying out earlier than longer ones. For a particular perturbed-shock
      system, the strength of the front and the EOS properties of the material through
      which it propagates determine the applicable family of solutions. Theoretical
      predictions agree well with FAST2D numerical simulations for several examples
      derived from the CALEOS library.

PMID- 15244939
TI  - "Clusterization" and intermittency of temperature fluctuations in turbulent
      convection.
AB  - Temperature time traces are obtained in turbulent thermal convection at high
      Rayleigh numbers. Measurements are made in the midplane of the apparatus, near
      the sidewall but outside the boundary layer. A telegraph approximation for
      temperature traces is generated by setting the fluctuation amplitude to 1 or 0
      depending on whether or not it exceeds the mean value. Unlike the standard
      diagnostics of intermittency, the telegraph approximation allows one to
      distinguish the tendency of events to cluster (clusterization) from their large
      scale variability in amplitude. A qualitative conclusion is that amplitude
      intermittency might mitigate clusterization effects.

PMID- 15244940
TI  - Long-term behavior of cooling fluid in a rectangular container.
AB  - In this study, the long-term behavior of cooling an initially quiescent
      isothermal Newtonian fluid in a rectangular container with an infinite length by
      unsteady natural convection due to a fixed wall temperature has been investigated
      by scaling analysis and direct numerical simulation. Two specific cases are
      considered. Case 1 assumes that the cooling of the fluid is caused by the imposed
      fixed temperature on the vertical sidewall while the top and bottom boundaries
      are adiabatic. Case 2 assumes that the cooling is caused by the imposed fixed
      temperature on both the vertical sidewall and the bottom boundary while the top
      boundary is adiabatic. The appropriate parameters to represent the long-term
      behavior of the fluid cooling in the container are the transient average fluid
      temperature T(a)(t) over the whole volume of the container per unit length (i.e.,
      the transient area average fluid temperature, as used in the subsequent numerical
      simulations) at time t and the average Nusselt number on the cooling boundary. A
      scaling analysis has been carried out which shows that for both cases
      theta(a)(tau) scales as e(-C(ARa)(-1/4) tau), where theta(a)(tau) is the
      dimensionless form of T(a)(t), tau is the dimensionless time, A is the aspect
      ratio of the container, Ra is the Rayleigh number, and C is a proportionality
      constant. A series of direct numerical simulations with the selected values of A,
      Ra, and Pr (Pr is the Prandtl number) in the ranges of 1/3< or =A< or =3, 6 x
      10(6) < or =Ra< or =6 x 10(10), and 1< or =Pr< or =1000 have been carried out for
      both cases to validate the developed scaling relations. It is found that these
      numerical results agree well with the scaling relations. The numerical results
      have also been used to quantify the scaling relations and it is found that
      C=0.645 and 0.705 respectively for Cases 1 and 2 with Ra, A and Pr in the above
      mentioned ranges.

PMID- 15244941
TI  - Log-stable laws as asymptotic solutions to a fragmentation equation: application
      to the distribution of droplets in a high Weber-number spray.
AB  - In this paper, it will be shown that "totally skewed to the left" log-stable
      distributions are suitable asymptotic solutions to a fragmentation equation. This
      result generalizes Kolmogorov's work on log-normal distribution for the drops'
      size number distribution of particles under pulverization. Indeed, Kolmogorov's
      discrete process is extended to a continuous time Markov process for the volume
      distribution instead of the number distribution. New hypotheses are then
      introduced which lead to log-stable distributions as asymptotic solutions of the
      fragmentation equation. Log-stable laws are then used to fit experimental
      probability distribution function (pdf) of Simmons and Hanratty measuring drop
      sizes in a horizontal annular gas-liquid flow at high Weber number [Int. J.
      Multiphase Flow 27, 861 (2001)]]. Log-stable pdf better fits to the experimental
      pdf than usual empirical spray pdf and especially, because of the heavy tail of
      the associated stable distribution, in the small drops part of the distribution.

PMID- 15244942
TI  - Formulation of turbulence mechanics.
AB  - This paper presents a setup of turbulence mechanics for averaged description of
      turbulence, founded on laws of momentum, moment of momentum, and energy,
      complemented by common rheological principles for formulating constitutive
      relations between generalized forces and generalized velocities of the
      description. A kinematical-geometrical principle is adopted to determine internal
      rotating degrees of freedom of turbulent media generated by the eddy structure of
      turbulent flow fields. The connection between the formulated mechanics and some
      models (as K-epsilon model), widely used in practical engineering flow
      calculations, is established. As an example, the formulated mechanics is applied
      to describe some classical flow patterns.

PMID- 15244943
TI  - Relaxation towards localized vorticity states in drift plasma and geostrophic
      flows.
AB  - The drift of ions in a magnetized plasma or the height fluctuations of a rotating
      fluid layer are described by the conservation equation of a potential vorticity.
      This potential vorticity contains an intrinsic length scale, the hybrid Larmor
      radius in plasma, and the Rossby length in the quasigeostrophic flow. The
      influence of this scale in the evolution of a random initial vorticity field is
      investigated using a thermodynamic approach. In contrast to the perfect fluid
      case, where the vorticity tends to a well defined stationary state, complete
      relaxation towards an equilibrium state is not observed in numerical simulations
      of quasigeostrophic decaying turbulence. The absence of global thermodynamic
      equilibrium is explained by the relaxation towards states of local equilibrium
      where the vorticity is concentrated. The interaction between these separated
      regions is extremely weak. Explicit, axisymmetric, localized solutions of the
      mean field integrodifferential equation of extremal entropy states are obtained
      using asymptotic methods. A comparison of the computed solutions with the
      observed coherent structures shows that they effectively correspond to states in
      local thermodynamic equilibrium.

PMID- 15244944
TI  - Horizontal thermocapillary convection of succinonitrile: steady state,
      instabilities, and transition to chaos.
AB  - We present the bifurcation pattern of the thermocapillary horizontal convection
      flow of succinonitrile (SCN) in an open top parallelepipedic cavity with
      dimensions 4 x 1 x 1. The bifurcation parameter is the Rayleigh number (Ra) that
      was investigated in the range [150;5x 10(8)] while the Marangoni number (Ma) was
      kept at Ma= 10(4). Several steady flow configurations are described for Ra< or =5
      x 10(7). Then the occurrence of periodic and quasiperiodic flows is shown for
      values of Ra<5 x 10(8) and at Ra=5 x 10(8) the chaos arises. It is also proved
      numerically the coexistence of different temporal regimes at the same value of Ra
      according to the thermal history of the fluid.

PMID- 15244945
TI  - Treatment of compounds and alloys in radiation hydrodynamics simulations of
      ablative laser loading.
AB  - Different methods were compared for constructing models of the behavior of a
      prototype intermetallic compound, nickel aluminide, for use in radiation
      hydrodynamics simulations of shock wave generation by ablation induced by laser
      energy. The models included the equation of state, ionization, and radiation
      opacity. The methods of construction were evaluated by comparing the results of
      simulations of an ablatively generated shock wave in a sample of the alloy. The
      most accurate simulations were obtained using the "constant number density"
      mixture model to calculate the equation of state and opacity, and Thomas-Fermi
      ionization. This model is consistent with that found to be most accurate for
      simulations of ablatively shocked elements.

PMID- 15244946
TI  - Parametric instabilities in magnetized multicomponent plasmas.
AB  - This paper investigates the excitation of various natural modes in a magnetized
      bi-ion or dusty plasma. The excitation is provided by parametrically pumping the
      magnetic field. Here two ionlike species are allowed to be fully mobile. This
      generalizes our previous work where the second heavy species was taken to be
      stationary. Their collection of charge from the background neutral plasma
      modifies the dispersion properties of the pump and excited waves. The
      introduction of an extra mobile species adds extra modes to both these types of
      waves. We first investigate the pump wave in detail, in the case where the
      background magnetic field is perpendicular to the direction of propagation of the
      pump wave. Then we derive the dispersion equation relating the pump to the
      excited wave for modes propagating parallel to the background magnetic field. It
      is found that there are a total of twelve resonant interactions allowed, whose
      various growth rates are calculated and discussed.

PMID- 15244947
TI  - Thermalization of a UV laser ablation plume in a background gas: From a directed
      to a diffusionlike flow.
AB  - Combined diagnostic measurements of deposition rates and ion time-of-flight
      signals have been employed to study the expansion of a laser ablation plume into
      a background gas. With increasing gas pressure the angular distribution of the
      collected ablated atoms becomes broader, while the total collected yield
      decreases. The total collected yield shows three separate regimes with increasing
      pressure, a vacuumlike regime, a transition regime with increasing plume
      broadening and splitting of the ion signal, and at the highest pressure a
      diffusionlike regime with a broad angular distribution. In the high-pressure
      regime the expansion can be described by a simple model based on diffusion from a
      confined plume.

PMID- 15244948
TI  - Ion temperature gradient instability in a dusty plasma.
AB  - An analysis of the temperature-gradient-driven ( eta(i) ) instability of drift
      waves in dusty plasma is presented. Various limits that allow for the coupling of
      the drift wave with the dynamics of dust grains are discussed. In particular, the
      cases of tiny (magnetized) and relatively heavy (unmagnetized) grains are
      studied. It is shown that in both limits the behavior of the eta(i) mode is
      considerably affected by the dust dynamics. The growth rate turns out to be
      higher in the presence of dust, and the instability threshold is lower, resulting
      in a more unstable plasma.

PMID- 15244949
TI  - X-ray line polarization of He-like Si satellite spectra in plasmas driven by high
      intensity ultrashort pulsed lasers.
AB  - We present a modeling study of x-ray line polarization in plasmas driven by high
      intensity, ultrashort duration pulsed lasers. Electron kinetics simulations of
      these transient and nonequilibrium plasmas predict non-Maxwellian and anisotropic
      electron distribution functions. Under these conditions, the magnetic sublevels
      within fine structure levels can be unequally populated which leads to the
      emission of polarized lines. We have developed a time-dependent, collisional
      radiative atomic kinetics model of magnetic sublevels to understand the
      underlying processes and mechanisms leading to the formation of polarized x-ray
      line emission in plasmas with anisotropic electron distribution functions. The
      electron distribution function consists of a thermal component extracted from
      hydrodynamic calculations and a beam component determined by PIC simulations of
      the laser-plasma interaction. We focus on the polarization properties of the He
      like Si satellites of the L y(alpha) line, discuss the time evolution of
      polarized satellite spectra, and identify suitable polarization markers that are
      sensitive to the anisotropy of the electron distribution function and can be used
      for diagnostic applications.

PMID- 15244950
TI  - Radiation reaction and relativistic hydrodynamics.
AB  - By invoking the radiation reaction force, first perturbatively derived by Landau
      and Lifschitz, and later shown by Rohrlich to be exact for a single particle, we
      construct a set of fluid equations obeyed by a relativistic plasma interacting
      with the radiation field. After showing that this approach reproduces the known
      results for a locally Maxwellian plasma, we derive and display the basic
      dynamical equations for a general magnetized plasma in which the radiation
      reaction force augments the direct Lorentz force.

PMID- 15244951
TI  - Magnetic helicity evolution in a periodic domain with imposed field.
AB  - In helical hydromagnetic turbulence with an imposed magnetic field (which is
      constant in space and time) the magnetic helicity of the field within a periodic
      domain is no longer an invariant of the ideal equations. Alternatively, there is
      a generalized magnetic helicity that is an invariant of the ideal equations. It
      is shown that this quantity is not gauge invariant and that it can therefore not
      be used in practice. Instead, the evolution equation of the magnetic helicity of
      the field describing the deviation from the imposed field is shown to be a useful
      tool. It is demonstrated that this tool can determine steady state quenching of
      the alpha-effect. A simple three-scale model is derived to describe the evolution
      of the magnetic helicity and to predict its sign as a function of the imposed
      field strength. The results of the model agree favorably with simulations.

PMID- 15244952
TI  - Parametric study of ion acceleration in a one-dimensional plasma expansion using
      the particle-in-cell simulation.
AB  - The one-dimensional expansion of a plasma off a planar wall into a vacuum is
      studied using particle-in-cell computer simulation. Particular emphasis is put on
      the acceleration of ions in the plasma. Energy transfer from the electronic to
      the ionic subsystem, the energy spectra of the ions, and the center-of-mass
      motion of the ion cloud are monitored. Various parameters that influence the
      acceleration process are studied: the presence of several ion charge states, of
      neutrals, the effects of a binary mixture of ions, and of a thermal
      nonequilibrium between ions and electrons.

PMID- 15244953
TI  - Numerical investigation of particle formation mechanisms in silane discharges.
AB  - The formation of particles in low-pressure silane discharges has been studied
      extensively over the last decade. In this paper we try to identify, by numerical
      simulations, the precursors of the dust formation and we examine the gas-phase
      reactions leading to larger clusters, and finally to nanometer or micrometer
      sized particles. A one-dimensional fluid model is used, which incorporates
      silicon hydrides (Si(n)H(m)) containing up to 12 silicon atoms. A set of 68
      species, including neutrals, radicals, ions, and electrons, is taken into
      account. The importance of various cluster reaction sequences is discussed.
      Besides the discussion of ion-molecule and ion-ion reactions, the role of the
      vibrationally excited silane molecules and of SiH3 radicals on the particle
      growth process is studied. Finally, the effect of temperature variation on the
      density of the dust particles is investigated.

PMID- 15244954
TI  - Electron acceleration by an intense short pulse laser in a static magnetic field
      in vacuum.
AB  - Electron acceleration by a laser pulse having Gaussian radial and temporal
      profiles of intensity has been studied in a static magnetic field in vacuum. The
      starting point of the magnetic field has been taken around the point where the
      peak of the pulse interacts with the electron and the direction of the static
      magnetic field is taken to be the same as that of the magnetic field of the laser
      pulse. The electron gains considerable energy and retains it in the form of
      cyclotron oscillations even after the passing of the laser pulse in the presence
      of an optimum static magnetic field. The optimum value of the magnetic field
      decreases with laser intensity and initial electron energy. The energy gain also
      depends upon the laser spot size and peaks for a suitable value. The energy
      gained by the electron increases with laser intensity and initial electron
      energy. The electron trajectory and energy gain for different parameters such as
      laser intensity, initial electron energy, and laser spot size have been
      presented.

PMID- 15244955
TI  - Finding a nonlinear lattice with improved integrability using Lie transform
      perturbation theory.
AB  - A condition for improved dynamic aperture for nonlinear, alternating gradient
      transport systems is derived using Lie transform perturbation theory. The Lie
      transform perturbation method is used here to perform averaging over fast
      oscillations by canonically transforming to slowly oscillating variables. This is
      first demonstrated for a linear sinusoidal focusing system. This method is then
      employed to average the dynamics over a lattice period for a nonlinear focusing
      system, provided by the use of higher order poles such as sextupoles and
      octupoles along with alternate gradient quadrupoles. Unlike the traditional
      approach, the higher order focusing is not treated as a perturbation. The Lie
      transform method is particularly advantageous for such a system where the form of
      the Hamiltonian is complex. This is because the method exploits the property of
      canonical invariance of Poisson brackets so that the change of variables is
      accomplished by just replacing the old ones with the new. The analysis shows the
      existence of a condition in which the system is azimuthally symmetric in the
      transformed, slowly oscillating frame. Such a symmetry in the time averaged frame
      renders the system nearly integrable in the laboratory frame. This condition
      leads to reduced chaos and improved confinement when compared to a system that is
      not close to integrability. Numerical calculations of single-particle
      trajectories and phase space projections of the dynamic aperture performed for a
      lattice with quadrupoles and sextupoles confirm that this is indeed the case.

PMID- 15244956
TI  - Electron bunch trapping and compression by an intense focused pulse laser.
AB  - A focused short-pulse laser of TEM (1,0)+TEM (0,1) mode has two intensity peaks
      in the radial direction, so that the transverse ponderomotive force may trap
      electrons between the two peaks. At the same time the longitudinal ponderomotive
      force may accelerate electrons at the head of the laser pulse, when the laser is
      focused. When the electrons move to the laser tail, the laser may diverge and the
      electron deceleration becomes relatively weak. Our numerical analyses demonstrate
      that electrons are trapped well by the laser potential well, and that at the same
      time the acceleration by the longitudinal ponderomotive force induces the
      electron bunch compression. This trapping and compression mechanism is unique:
      the electron bunch can be compressed to the scale of the laser pulse length.

PMID- 15244957
TI  - Collisional dynamics of vortices in light condensates.
AB  - Through numerical simulation, we have studied the nucleation and annihilation of
      two-dimensional optical vortex solitons hosted in finite size light beams. Our
      study covers a wide range of angular momentum l> or =1, also referred to as its
      topological charge. We demonstrate that surface tension of light beams prevents
      beam filamentation for a certain range of total reflection angles even if the
      hosted hole splits and decays into several vortices with lower values of l. We
      also discuss a mechanism for vortex nucleation starting from Gaussian beams that
      can be used for experimental purposes. Our work adds extra support to the idea
      that light beams in cubic-quintic nonlinear materials can undergo a phase
      transition from a photon gas to a liquid of light.

PMID- 15244958
TI  - Passive system with tunable group velocity for propagating electrical pulses from
      sub- to superluminal velocities.
AB  - We report an observation of tunable group velocity from sub-luminal to
      superluminal in a completely passive system. Electric pulses are sent along a
      spatially periodic conducting medium containing a punctual nonlinearity, and the
      resulting amplitude-dependent phase shift allows us to control dispersion and the
      propagation velocity at the stop band frequency.

PMID- 15244959
TI  - Gap maps and intrinsic diffraction losses in one-dimensional photonic crystal
      slabs.
AB  - A theoretical study of photonic bands for one-dimensional (1D) lattices embedded
      in planar waveguides with strong refractive index contrast is presented. The
      approach relies on expanding the electromagnetic field on the basis of guided
      modes of an effective waveguide, and on treating the coupling to radiative modes
      by perturbation theory. Photonic mode dispersion, gap maps, and intrinsic
      diffraction losses of quasi guided modes are calculated for the case of self
      standing membranes as well as for silicon-on-insulator structures. Photonic band
      gaps in a waveguide are found to depend strongly on the core thickness and on
      polarization, so that the gaps for transverse electric and transverse magnetic
      modes most often do not overlap. Radiative losses of quasiguided modes above the
      light line depend in a nontrivial way on structure parameters, mode index, and
      wave vector. The results of this study may be useful for the design of integrated
      1D photonic structures with low radiative losses.

PMID- 15244960
TI  - Finite-size effect on one-dimensional coupled-resonator optical waveguides.
AB  - We study the finite-size effect on the dispersion relation, group velocity, and
      transmission curves of one-dimensional finite-size coupled-resonator optical
      waveguide (CROW) structures. Both the dispersion relation and the group velocity
      curves of a finite-size CROW oscillate along those of the corresponding infinite
      extended ones. The oscillations can be suppressed by matching the equivalent
      admittance of the surrounding medium to that of the unit cell. Thelen's method is
      used to find the parameters of the matching layer to reduce oscillations on the
      group velocity and transmission spectra, and to analyze the structure parameters
      that determine the bandwidth and the group velocity.

PMID- 15244961
TI  - Three-wave solitons and continuous waves in media with competing quadratic and
      cubic nonlinearities.
AB  - We formulate a general model of three-wave optical interactions (in the spatial
      domain), which combines quadratic (chi(2)) and cubic (chi(3)) nonlinearities, the
      latter including four-wave mixing. The model can be realized in chi(2) materials
      where an effective chi(3) nonlinearity is engineered by means of the quasi-phase
      matching technique. Both self-focusing and self-defocusing chi(3) nonlinearities
      are considered. The birefringence of the two fundamental-frequency (FF) waves is
      taken into regard. Several types of solitons in this system are found, by means
      of the variational approximation and numerical methods. These are exact single
      component solitons and generic three-wave (3W) ones, which are classified by
      relative signs of their components. Stability of the solitons is investigated by
      means of the Vakhitov-Kolokolov (VK) criterion, and then tested by direct
      simulations. One type of the single-component FF solitons (the "fast" one, in
      terms of the known two-component birefringent chi(3) model) is, chiefly,
      unstable, as in that model, but nevertheless a stability interval is found for
      it, which provides for the first example of stable fast solitons. The other FF
      soliton (the "slow" one, in terms of the same chi(3) model, where it is always
      stable) has its stability and instability regions. A single-component soliton in
      the second harmonic (SH) is found too; it also has its stability region, contrary
      to the common belief that such a soliton must always be unstable due to the
      parametric interaction. The 3W solitons are stable indeed if this is predicted by
      the VK condition, in the case when all the three components are positive.
      Following variation of the chi(2) mismatch parameter, the 3W soliton bifurcates
      from the SH one, and at another point it bifurcates back into the slow-FF single
      component soliton; conjectured normal forms of the respective bifurcations are
      given. 3W solitons with different signs of their components may be unstable
      contrary to the VK criterion, which is explained by consideration of the chi(2)
      term in the system's Hamiltonian. In direct simulations, unstable solitons evolve
      into stable breathers. A different instability takes place in the case of the
      self-defocusing chi(3) nonlinearity, when all the solitons blow up into a
      turbulent state. Parallel to the solitons, continuous-wave solutions are studied
      too. In terms of the existence and stability, they resemble solitons of similar
      types.

PMID- 15244962
TI  - Range of validity of the Rayleigh hypothesis.
AB  - The parameter range over which the Rayleigh hypothesis (RH) for optical gratings
      might be validly applied to analysis of high power backward wave oscillators has
      been investigated numerically. It had been pointed out that from a rigorous
      mathematical viewpoint, RH was only valid for a shallow corrugation of slow wave
      structure (SWS) such that h K0 <0.448; here, h and K0 are, respectively, the
      amplitude and wave number of the periodicity in a sinusoidal planar grating. We
      numerically analyze the electromagnetic fields in the axisymmetric SWS with and
      without use of RH. The field patterns and eigenfrequency for the SWS are solved
      numerically for a given k(z) by using the code HIDM (higher order implicit
      difference method) that is free from the RH. It is found that, for a deep
      corrugation, h K0 =5 x 0.448, using RH is still valid for obtaining the
      dispersion relation, although the Floquet harmonic expansion (FHE) fails to
      correctly represent the field patterns inside the corrugation. Accordingly, there
      exists a discrepancy between the validity of using RH for obtaining dispersion
      relations and for an exact convergence of FHE everywhere in the SWS.

PMID- 15244963
TI  - Dynamics of the Ablowitz-Ladik soliton train.
AB  - It is shown that dynamics of a train of N weakly interacting Ablowitz-Ladik
      solitons with (almost) equal velocities and masses is governed by the complex
      Toda chain model. The integrability of the complex Toda chain model provides the
      means to describe analytically various dynamical regimes of the N-soliton train
      and to predict initial soliton parameters responsible for each of the regimes.
      Numerical simulations corroborate well analytical predictions. A specific feature
      arising for the discrete soliton train system is the appearance of an additional
      (with respect to the lattice spacing) spatial scale-intersoliton distance. We
      comment on interplay between both spatial scales.

PMID- 15244964
TI  - Ray and wave instabilities in twisted graded-index optical fibers.
AB  - We study ray and wave propagation in an elliptical graded-index optical fiber or
      lens with a twisted axis and show analytically the existence of an instability
      for both ray trajectories and beam moments in a finite range of axis twist rate
      embedded within the spatial frequencies of periodically focused rays for the
      untwisted fiber. By considering the paraxial ray equations and the paraxial wave
      dynamics in a rotating frame that follows the fiber axis twist, we reduce the
      dynamical problem of ray trajectories to the classical Blackburn's pendulum,
      which shows a dynamical instability, corresponding to classical diverging
      trajectories, due to the competing effects of confining potential, Coriolis
      force, and centrifugal force. A closed set of linear evolution equations for
      generalized beam moments are also derived from the paraxial wave equation in the
      rotating reference frame, revealing the existence of a dynamical moment
      instability in addition to the trajectory instability. A detailed analysis of
      beam propagation is presented in case of a Gaussian beam, and different dynamical
      regimes are discussed.

PMID- 15244965
TI  - Breather statics and dynamics in Klein-Gordon chains with a bend.
AB  - In this paper, we examine a nonlinear model with an impurity emulating a bend. We
      justify the geometric interpretation of the model and connect it with earlier
      work on models including geometric effects. We focus on both the bifurcation and
      stability analysis of the modes that emerge as a function of the strength of the
      bend angle, but we also examine dynamical effects including the scattering of
      mobile localized modes (discrete breathers) off of such a geometric structure.
      The potential outcomes of such numerical experiments (including transmission,
      trapping within the bend as well as reflection) are highlighted and qualitatively
      explained. Such models are of interest both theoretically in understanding the
      interplay of breathers with curvature, but also practically in simple models of
      photonic crystals or of bent chains of DNA.

PMID- 15244966
TI  - Rolling and slipping motion of Euler's disk.
AB  - We present an experimental study of the motion of a circular disk spun onto a
      table. With the help of a high speed video system, the temporal evolution of (i)
      the inclination angle alpha, (ii) the angular velocity omega, and (iii) the
      precession rate Omega are studied. The influence of the mass of the disk as well
      as the friction between the disk and the supporting surface are considered. Both
      inclination angle and angular velocity are observed to decrease according to a
      power law. We also show that the precession rate diverges as the motion stops.
      Measurements are performed very near the collapse as well as on long range times.
      Times to collapse have been also measured. Results are compared with previous
      theoretical and experimental works. The major source of energy dissipation is
      found to be the slipping of the disk on the plane.

PMID- 15244967
TI  - One-dimensional nondiffracting pulses.
AB  - A general expression describing nondiffracting pulses whose transverse profile is
      a one-dimensional image is presented. The pulse turns out to be expressed as a
      superposition of two fields, possessing a purely translational dynamics, whose
      profiles are related to the field distribution on the the waist plane through an
      Hilbert transformation. The space-time structure of the generally X-shaped pulse
      is investigated and a simple relation connecting its transverse and the
      longitudinal widths is established. Specific analytical examples are considered
      and, in particular, the fundamental one-dimensional X waves are deduced and
      compared to their two-dimensional counterparts.

PMID- 15244968
TI  - Soliton ratchets induced by excitation of internal modes.
AB  - Recently Phys. Rev. Lett. 88, 184101 (2002)]] used a symmetry analysis to predict
      the appearance of directed energy current in homogeneously spatially extended
      systems coupled to a heat bath in the presence of an external ac field E (t).
      Their symmetry analysis allowed them to make the right choice of E (t) so as to
      obtain symmetry breaking which causes directed energy transport for systems with
      a nonzero topological charge. Their numerical simulations verified the existence
      of the directed energy current. They argued that the origin of their strong
      rectification in the underdamped limit is due to the excitation of internal modes
      and their interaction with the translational kink motion. The internal mode
      mechanism as a cause of current rectification was also proposed by Salerno and
      Zolotaryuk [Phys. Rev. E. 65, 056603 (2002)]]. We use a rigorous collective
      variable for nonlinear Klein-Gordon equations to prove that the rectification of
      the current is due to the excitation of an internal mode Gamma (t), which
      describes the oscillation of the slope of the kink, and due to a dressing of the
      bare kink by the ac driver. The internal mode Gamma (t) is excited by its
      interaction with the center of mass of the kink, X (t), which is accelerated by E
      (t). The external field E (t) also causes the kink to be dressed. We derive the
      expressions for the dressing and numerically solve the equations of motion for
      Gamma (t), X (t), and the momentum P (t), which enable us to obtain the explicit
      expressions for the directed energy current and the ac driven kink profile. We
      then show that the directed energy current vanishes unless the slope Gamma (t) is
      a dynamical variable and the kink is dressed by the ac driver.

PMID- 15244969
TI  - Light angular momentum flux and forces in birefringent inhomogeneous media.
AB  - The angular momentum carried by a monochromatic optical field is separated into
      an orbital and a spin part beyond the paraxial approximation. These quantities
      have been distinguished on the grounds of the different mechanical effects they
      produce in transparent and birefringent media endowed with internal degrees of
      freedom. The orbital and the spin angular momentum flux densities exhibited are
      shown to be divergence free in homogeneous and isotropic media and to give back
      the correct expressions in the paraxial limit.

PMID- 15244970
TI  - Electromagnetic scattering by optically anisotropic magnetic particle.
AB  - The Mie theory for electromagnetic scattering by spherical particle is extended
      to the case of magnetic particle with gyromagnetic type of permeability.
      Specifically, we first construct for the magnetic induction B(I) inside the
      particle a new set of vector basis functions, which are the solution of the wave
      equation for B(I) and expanded in terms of the usual vector spherical wave
      functions (VSWF's) with different values of wave vector k(l). The relationship
      between k(l) and the frequency is obtained as the eigenvalues of an eigensystem
      determined by the permeability tensor. The incident and scattered fields are
      expanded as usual in terms of the VSWF's. By matching the boundary conditions, a
      linear set of coupled equations for the expansion coefficients are obtained and
      then solved for the solution to the scattering problem. Preliminary numerical
      results are presented for the case in which the scattering is due solely to the
      optical anisotropy within the particle. The scattering efficiency is found to
      exhibit miscellaneous dependence on the incident angle, the polarization, the
      degree of anisotropy, as well as the size parameter. In addition, the possibility
      of the photonic Hall effect for one Mie scatterer is confirmed.

PMID- 15244971
TI  - Existence of short-time approximations of any polynomial order for the
      computation of density matrices by path integral methods.
AB  - In this paper I provide significant mathematical evidence in support of the
      existence of direct short-time approximations of any polynomial order for the
      computation of density matrices of physical systems described by arbitrarily
      smooth and bounded from below potentials. While for Theorem 2, which is
      "experimental," I only provide a "physicist's" proof, I believe the present
      development is mathematically sound. As a verification, I explicitly construct
      two short-time approximations to the density matrix having convergence orders 3
      and 4, respectively. Furthermore, in Appendix B, I derive the convergence
      constant for the trapezoidal Trotter path integral technique. The convergence
      orders and constants are then verified by numerical simulations. While the two
      short-time approximations constructed are of sure interest to physicists and
      chemists involved in Monte Carlo path integral simulations, the present paper is
      also aimed at the mathematical community, who might find the results interesting
      and worth exploring. I conclude the paper by discussing the implications of the
      present findings with respect to the solvability of the dynamical sign problem
      appearing in real-time Feynman path integral simulations.

PMID- 15244972
TI  - Lattice Boltzmann method for the compressible Euler equations.
AB  - The lattice Boltzmann model for the compressible Euler equations is proposed
      together with its rigorous theoretical background. The proposed model has
      completely overcome the defects of the previous model that the specific-heat
      ratio cannot be chosen freely. The macroscopic variables obtained from the
      solution are shown to satisfy, in the limit of the small Knudsen number, the
      compressible Euler equations if the variation of the solution is moderate. This
      is the case where no shock waves or contact discontinuities appear. In contrast,
      when the solution makes steep variation at several localized regions due to the
      appearance of shock waves and contact discontinuities, the corresponding
      macroscopic variables satisfy the weak form of the Euler equations. Their
      derivation is carried out rigorously by taking into account the scale of
      variation of the solution correctly. This is the first study that has laid the
      theoretical foundation of the lattice Boltzmann model for the simulation of flows
      with shock waves and contact discontinuities. Numerical examples and the error
      estimates are also given, which are consistent with the above theoretical
      arguments.

PMID- 15244973
TI  - Magnetization curves as probes of Monte Carlo simulation of nonequilibrium
      states.
AB  - The influence of parameter choice in the Monte Carlo simulation of zero-field
      cooled-field-cooled magnetization curves of granular systems is analyzed. The
      main simulation techniques are summarized and compared, in terms of the
      determination of macroscopic quantities usually associated with nanoscopic
      details of the sample.

PMID- 15244974
TI  - Adaptive integration method for Monte Carlo simulations.
AB  - We present an adaptive sampling method for computing free energies, radial
      distribution functions, and potentials of mean force. The method is characterized
      by simplicity and accuracy, with the added advantage that the data are obtained
      in terms of quasicontinuous functions. The method is illustrated and tested with
      simulations on a high density fluid, including a stringent consistency test
      involving an unusual thermodynamic cycle that highlights its advantages.

PMID- 15244975
TI  - Heisenberg-Fisher thermal uncertainty measure.
AB  - We establish a connection among (i) the so-called Wehrl entropy, (ii) Fisher's
      information measure I(beta), and (iii) the canonical ensemble entropy for the one
      dimensional quantum harmonic oscillator (HO). We show that the contribution of
      the excited HO spectrum to the mean thermal energy is given by I(beta), while the
      pertinent canonical partition function is essentially given by another Fisher
      measure: the so-called shift invariant one. Our findings should be of interest in
      view of the fact that it has been shown that the Legendre transform structure of
      thermodynamics can be replicated without any change if one replaces the Boltzmann
      Gibbs-Shannon entropy by Fisher's information measure [Phys. Rev. E 60, 48
      (1999)]]. Fisher-related uncertainty relations are also advanced, together with a
      Fisher version of thermodynamics' third law.

PMID- 15244976
TI  - Density fluctuations near the liquid-gas critical point of a confined fluid.
AB  - We report the results of an experimental study of the effect of a dilute silica
      network on liquid-gas critical phenomena in carbon dioxide (CO2). Using small
      angle neutron scattering, we measured the correlation length of the density
      fluctuations in bulk (xi(bulk)) and confined CO2 (xi(conf)) as a function of
      temperature and average fluid density. We find that quenched disorder induced by
      an aerogel suppresses density fluctuations: xi(conf) loses the Ising model
      divergence characteristic of xi(bulk) and does not exceed the size of pores in
      the homogeneous region.

PMID- 15244977
TI  - Wealth accumulation with random redistribution.
AB  - We study the wealth distribution in random multiplicative processes with random
      redistribution. The equilibrium distribution can be extended to the negative
      wealth. The extreme wealths follow power law distributions and the same exponent
      is found for both the large wealths and the large debts. We propose a mean-field
      model to emphasize the fluctuations in the thermodynamic limit. The exact
      solution can be obtained analytically.

PMID- 15244978
TI  - Cellular automata on high-dimensional hypercubes.
AB  - The emergence of nontrivial collective behavior is studied in large families of
      cellular automata rules implemented on high-dimensional hypercubes. Evidence is
      found that the region of rule space where such macroscopic dynamics exists is
      well-defined in the infinite-dimension limit.

PMID- 15244979
TI  - Statistics of active versus passive advections in magnetohydrodynamic turbulence.
AB  - Active turbulent advection is considered in the context of magnetohydrodynamics.
      In this case, an auxiliary passive field bears no apparent connection to the
      active field. The scaling properties of the two fields are different. In the
      framework of a shell model, we show that the two-point structure function of the
      passive field has a unique zero mode, characterizing the scaling of this field
      only. In other words, the existence of statistical invariants for the decaying
      passive field carries no information on the scaling properties of the active
      field.

PMID- 15244980
TI  - Electromagnetic density of modes for a finite-size three-dimensional structure.
AB  - The concept of the density of modes has been lacking a precise mathematical
      definition for a finite-size structure. With the explosive growth in the
      fabrication of photonic crystals and nanostructures, which are inherently finite
      in size, a workable definition is imperative. We give a simple and physically
      intuitive definition of the electromagnetic density of modes based on the Green's
      function for a generic three-dimensional open cavity filled with a linear,
      isotropic, dielectric material.

PMID- 15244981
TI  - Plane-wave diffraction at the periodically corrugated boundary of vacuum and a
      negative-phase-velocity material.
AB  - Considering the diffraction of a plane wave by a periodically corrugated half
      space, we show that the transformation of the refracting medium from positive
      (negative) phase velocity to negative (positive) phase velocity type has an
      influence on the diffraction efficiencies. This effect increases with increasing
      corrugation depth, owing to the presence of evanescent waves in the troughs of
      the corrugated interface.

PMID- 15244982
TI  - Real-time analysis of the telegrapher's equation for tunneling processes.
AB  - Based on a close analogy with an RLC circuit, a model for interpreting delay
      times in forbidden regimes (tunneling) is formulated, avoiding the analytical
      continuation into imaginary time. In this way, a reasonable description of
      experimental data, which were previously reported for a waveguide propagation
      below the cutoff frequency at approximately 9.5 GHz, is obtained.

PMID- 15244983
TI  - Random phase vector for calculating the trace of a large matrix.
AB  - We derive an estimate of the statistical error in calculating the trace of a
      large matrix by using random vectors, and show that the random phase vector gives
      the results with the smallest statistical error for a given basis set. This
      result supports use of random phase vectors in the calculation of density of
      states and linear response functions of large quantum systems.

PMID- 15244984
TI  - Using overlap and funnel sampling to obtain accurate free energies from
      nonequilibrium work measurements.
AB  - Two concepts are presented for accurate nonequilibrium work free-energy
      measurements, realized both in molecular simulation and experiment. First, the
      need for an intermediate important to both the reference and the target systems
      (overlap) is indicated. Second, the use of a soft path from each end point to the
      intermediate (funnel) is demonstrated. Schemes implementing these concepts
      dramatically improve efficiency and accuracy of free energy calculations, as
      shown by calculation of the free energy of ion charging in water, and the free
      energy change in mutation of an adenosine molecule.

PMID- 15244985
TI  - Nucleation and growth in pressure-induced phase transitions from molecular
      dynamics simulations: mechanism of the reconstructive transformation of NaCl to
      the CsCl-type structure.
AB  - We perform path sampling molecular dynamics on the pressure-induced
      reconstructive phase transition from NaCl to CsCl type structure. Unlike the
      molecular dynamics simulations prior to this work our approach does not drive the
      process by applying elevated pressure. As a consequence, we are able to observe
      nucleation events that initiate the successive transformation of the crystal. The
      competing phases are separated by an interface exhibiting a well-defined
      structure that propagates through the crystal during phase transition.

PMID- 15244986
TI  - Exact hydrodynamics of a trapped dipolar Bose-Einstein condensate.
AB  - We present exact results in the Thomas-Fermi regime for the statics and dynamics
      of a harmonically trapped Bose-Einstein condensate that has dipole-dipole
      interactions in addition to the usual s-wave contact interactions. Remarkably,
      despite the nonlocal and anisotropic nature of the dipolar interactions, the
      density profile in a general time-dependent harmonic trap is an inverted
      parabola. The evolution of the condensate radii is governed by local, ordinary
      differential equations, and as an example we calculate the monopole and
      quadrupole shape oscillation frequencies.

PMID- 15244987
TI  - External time-varying fields and electron coherence.
AB  - The effect of time-varying electromagnetic fields on electron coherence is
      investigated. A sinusoidal electromagnetic field produces a time-varying Aharonov
      Bohm phase. In a measurement of the interference pattern which averages over this
      phase, the effect is a loss of contrast. This is effectively a form of
      decoherence. We calculate the magnitude of this effect for various
      electromagnetic field configurations. The result seems to be sufficiently large
      to be observable.

PMID- 15244988
TI  - Superfluidity of trapped dipolar fermi gases.
AB  - We derive the phase diagram for ultracold trapped dipolar Fermi gases. Below the
      critical value of the dipole-dipole interaction energy, the BCS transition into a
      superfluid phase ceases to exist. The critical dipole strength is obtained as a
      function of the trap aspect ratio. Alternatively, for a given dipole strength
      there is a critical value of the trap anisotropy for the BCS state to appear. The
      order parameter exhibits a novel nonmonotonic behavior at the criticality.

PMID- 15244989
TI  - Coincidence bell inequality for three three-dimensional systems.
AB  - We construct a Bell inequality for coincidence probabilities on a three three
      dimensional (qutrit) system. We show that this inequality is violated when each
      observer measures two noncommuting observables, defined by the so-called unbiased
      six-port beam splitter, on a maximally entangled state of two qutrits. The
      strength of the violation agrees with the numerical results presented by
      Kaszlikowski et al, quant-ph/0202019. It is proven that the inequality defines
      facets of the polytope of local variable models.

PMID- 15244990
TI  - Diffusion on a solid surface: anomalous is normal.
AB  - We present a numerical study of classical particles diffusing on a solid surface.
      The particles' motion is modeled by an underdamped Langevin equation with
      ordinary thermal noise. The particle-surface interaction is described by a
      periodic or a random two-dimensional potential. The model leads to a rich variety
      of different transport regimes, some of which correspond to anomalous diffusion
      such as has recently been observed in experiments and Monte Carlo simulations. We
      show that this anomalous behavior is controlled by the friction coefficient and
      stress that it emerges naturally in a system described by ordinary canonical
      Maxwell-Boltzmann statistics.

PMID- 15244991
TI  - Coagulation by random velocity fields as a Kramers problem.
AB  - We analyze the motion of a system of particles suspended in a fluid which has a
      random velocity field. There are coagulating and noncoagulating phases. We show
      that the phase transition is related to a Kramers problem, and we use this to
      determine the phase diagram in two dimensions, as a function of the dimensionless
      inertia of the particles, epsilon, and a measure of the relative intensities of
      potential and solenoidal components of the velocity field, Gamma. We find that
      the phase line is described by a function which is nonanalytic at epsilon=0, and
      which is related to escape over a barrier in the Kramers problem. We discuss the
      physical realizations of this phase transition.

PMID- 15244992
TI  - Sneutrino condensate source for density perturbations, leptogenesis, and low
      reheat temperature.
AB  - We bring together some known ingredients beyond the standard model physics that
      can explain the hot big bang model with the observed baryon asymmetry and also
      the fluctuations in the cosmic microwave background radiation with a minimal set
      of assumptions. We propose an interesting scenario where the inflaton energy
      density is dumped into an infinitely large extra dimension. Instead of the
      inflaton it is the right handed sneutrino condensate, which is acquiring a
      nonzero vacuum expectation value during inflation, whose fluctuations are
      responsible for the density perturbations seen in the cosmic microwave background
      radiation with a spectral index n(s) approximately 1. The decay of the condensate
      is explaining the reheating of the Universe with a temperature, T(rh)< or =10(9)
      GeV, and the baryon asymmetry of order one part in 10(10) with no baryon
      isocurvature fluctuations.

PMID- 15244993
TI  - D-term inflation without cosmic strings.
AB  - We present a superstring-inspired version of D-term inflation that does not lead
      to cosmic string formation and appears to satisfy the current cosmic microwave
      background constraints. It differs from minimal D-term inflation by a second pair
      of charged superfields that makes the strings nontopological (semilocal). The
      strings are also Bogomol'nyi-Prasad-Sommerfield strings, so the scenario is
      expected to survive supergravity corrections. The second pair of charged
      superfields arises naturally in several brane and conifold scenarios, but its
      effect on cosmic string formation had not been noticed so far.

PMID- 15244994
TI  - Unified model for vortex-string network evolution.
AB  - We describe and numerically test the velocity-dependent one-scale string
      evolution model, a simple analytic approach describing a string network with the
      averaged correlation length and velocity. We show that it accurately reproduces
      the large-scale behavior (in particular the scaling laws) of numerical
      simulations of both Goto-Nambu and field theory string networks. We explicitly
      demonstrate the relation between the high-energy physics approach and the damped
      and nonrelativistic limits which are relevant for condensed matter physics. We
      also reproduce experimental results in this context and show that the vortex
      string density is significantly reduced by loop production, an effect not
      included in the usual "coarse-grained" approach.

PMID- 15244997
TI  - Semileptonic hyperon decays and Cabibbo-Kobayashi-Maskawa unitarity.
AB  - Using a technique that is not subject to first-order SU(3) symmetry breaking
      effects, we determine the V(us) element of the Cabibbo-Kobayashi-Maskawa matrix
      from data on semileptonic hyperon decays. We obtain V(us)=0.2250(27), where the
      quoted uncertainty is purely experimental. This value is of similar experimental
      precision to the one derived from K(l3), but it is higher and thus in better
      agreement with the unitarity requirement, |V(ud)|(2)+|V(us)|(2)+|V(ub)|(2)=1. An
      overall fit, including the axial contributions and neglecting SU(3) breaking
      corrections, yields F+D=1.2670 +/-0.0035 and F-D=-0.341+/-0.016 with
      chi(2)=2.96/3 degrees of freedom.

PMID- 15244999
TI  - Enhanced stability of superheavy nuclei due to high-spin isomerism.
AB  - Configuration-constrained calculations of potential-energy surfaces in even-even
      superheavy nuclei reveal systematically the existence at low excitation energies
      of multiquasiparticle states with deformed axially symmetric shapes and large
      angular momenta. These results indicate the prevalence of long-lived,
      multiquasiparticle isomers. In a quantal system, the ground state is usually more
      stable than the excited states. In contrast, in superheavy nuclei the
      multiquasiparticle excitations decrease the probability for both fission and
      alpha decay, implying enhanced stability. Hence, the systematic occurrence of
      multiquasiparticle isomers may become crucial for future production and study of
      even heavier nuclei. The energies of multiquasiparticle states and their alpha
      decays are calculated and compared to available data.

PMID- 15244998
TI  - Photoproduction of eta-mesic 3He.
AB  - The photoproduction of eta-mesic 3He has been investigated using the TAPS
      calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive
      cross section for the reaction gamma3He-->etaX has been measured for photon
      energies from threshold to 820 MeV. The total and angular differential coherent
      eta cross sections have been extracted up to energies of 745 MeV. A resonancelike
      structure just above the eta production threshold with an isotropic angular
      distribution suggests the existence of a resonant quasibound state. This is
      supported by studies of a competing decay channel of such a quasibound eta-mesic
      nucleus into pi(0)pX. A binding energy of (-4.4+/-4.2) MeV and a width of (25.6+/
      6.1) MeV is deduced for the quasibound eta-mesic state in 3He.

PMID- 15245000
TI  - High-spin structure beyond band termination in 157Er.
AB  - The angular-momentum induced transition from a deformed state of collective
      rotation to a noncollective configuration has been studied. In 157Er this
      transition manifests itself as favored band termination near I=45 Planck's. The
      feeding of these band terminating states has been investigated for the first time
      using the Gammasphere spectrometer. Many weakly populated states lying at high
      excitation energy that decay into these special states have been discovered.
      Cranked Nilsson-Strutinsky calculations suggest that these states arise from
      weakly collective "core-breaking" configurations.

PMID- 15245001
TI  - Bloch oscillations of ultracold atoms: a tool for a metrological determination of
      h/m Rb.
AB  - We use Bloch oscillations in a horizontal moving standing wave to transfer a
      large number of photon recoils to atoms with a high efficiency (99.5% per cycle).
      By measuring the photon recoil of 87Rb, using velocity-selective Raman
      transitions to select a subrecoil velocity class and to measure the final
      accelerated velocity class, we have determined h/m(Rb) with a relative precision
      of 0.4 ppm. To exploit the high momentum transfer efficiency of our method, we
      are developing a vertical standing wave setup. This will allow us to measure
      h/m(Rb) better than 10(-8) and hence the fine structure constant alpha with an
      uncertainty close to the most accurate value coming from the (g-2) determination.

PMID- 15245002
TI  - Radiative lifetime of a bound excited state of Te-.
AB  - We report on the first experimental study of the lifetime of a bound excited
      state of a negative ion. A new experimental technique was developed and used to
      measure the radiative lifetime of the 5p(5) (2)P(1/2) level of Te-. The
      experiment was performed in a magnetic storage ring, where a laser beam was
      applied along one of the straight sections. In the experiment the population of
      the excited J=1/2 level was probed each time the Te- ions passed through the
      laser field. A decay curve was built up by sampling the population of the excited
      level of the Te- ions as a function of time after injection into the ring. A
      multiconfiguration Dirac-Hartree-Fock calculation was performed in conjunction
      with the experiment. The calculation yielded a radiative lifetime of 0.45 s, in
      excellent agreement with the measured value of 0.42(5) s.

PMID- 15245003
TI  - Electron temperature of ultracold plasmas.
AB  - We study the evolution of ultracold plasmas by measuring the electron
      temperature. Shortly after plasma formation, competition between heating and
      cooling mechanisms drives the electron temperature to a value within a narrow
      range regardless of the initial energy imparted to the electrons. In agreement
      with theory predictions, plasmas exhibit values of the Coulomb coupling parameter
      Gamma less than 1.

PMID- 15245004
TI  - Sagnac interferometry based on ultraslow polaritons in cold atomic vapors.
AB  - The advantages of light and matter-wave Sagnac interferometers--large area on one
      hand and high rotational sensitivity per unit area on the other--can be combined
      utilizing ultraslow light in cold atomic gases. While a group-velocity reduction
      alone does not affect the Sagnac phase shift, the associated momentum transfer
      from light to atoms generates a coherent matter-wave component which gives rise
      to a substantially enhanced rotational signal. It is shown that matter-wave
      sensitivity in a large-area interferometer can be achieved if an optically dense
      vapor at subrecoil temperatures is used. Already a noticeable enhancement of the
      Sagnac phase shift is possible, however, with far fewer cooling requirements.

PMID- 15245005
TI  - Dynamic nonlinear X waves for femtosecond pulse propagation in water.
AB  - Recent experiments involving femtosecond pulses in water displayed long-distance
      propagation analogous to that reported in air. We verify this phenomenon
      numerically and show that the propagation is dynamic as opposed to self-guided.
      Furthermore, we demonstrate that the propagation can be interpreted as being due
      to dynamic nonlinear X waves whose robustness and role in long-distance
      propagation follows from the interplay between nonlinearity and chromatic
      dispersion.

PMID- 15245006
TI  - Incomplete photonic band gap as inferred from the speckle pattern of scattered
      light waves.
AB  - Motivated by recent experiments on intensity correlations of the waves
      transmitted through disordered media, we demonstrate that the speckle pattern
      from disordered photonic crystal with incomplete band gap represents a sensitive
      tool for determination of the stop-band width. We establish the quantitative
      relation between this width and the angular anisotropy of the intensity
      correlation function.

PMID- 15245007
TI  - Light filaments without self-channeling.
AB  - The propagation of intense 200 fs pulses in water reveals light filaments not
      sustained by static balance between Kerr-induced self-focusing and plasma-induced
      defocusing. Numerical calculations outline the occurrence of a possible scenario
      where filaments appear because of spontaneous reshaping of the Gaussian input
      beam into a conical wave, driven by the requirement of maximum localization,
      maximum stationarity, and minimum nonlinear losses.

PMID- 15245008
TI  - Photonic band-gap inhibition of modulational instabilities.
AB  - Spatial structures as a result of a modulational instability are studied in a
      nonlinear cavity with a photonic crystal. The interaction of the modulated
      refractive index with the nonlinearity inhibits the instability via the creation
      of a photonic band gap. A novel mechanism of light localization due to defects
      and pattern inhibition is also described.

PMID- 15245009
TI  - Ultralow loss, high Q, four port resonant couplers for quantum optics and
      photonics.
AB  - We demonstrate a low-loss, optical four port resonant coupler (add-drop
      geometry), using ultrahigh Q (>10(8)) toroidal microcavities. Different regimes
      of operation are investigated by variation of coupling between resonator and
      fiber taper waveguides. As a result, waveguide-to-waveguide power transfer
      efficiency of 93% (0.3 dB loss) and nonresonant insertion loss of 0.02% (<0.001
      dB) for narrow bandwidth (57 MHz) four port couplers are achieved in this work.
      The combination of low-loss, fiber compatibility, and wafer-scale design would be
      suitable for a variety of applications ranging from quantum optics to photonic
      networks.

PMID- 15245010
TI  - Noise-induced macroscopic bifurcations in globally coupled chaotic units.
AB  - Large populations of globally coupled identical maps subjected to independent
      additive noise are shown to undergo qualitative changes as the features of the
      stochastic process are varied. We show that, for strong coupling, the collective
      dynamics can be described in terms of a few effective macroscopic degrees of
      freedom, whose deterministic equations of motion are systematically derived
      through an order parameter expansion.

PMID- 15245011
TI  - Logarithmic periodicities in the bifurcations of type-I intermittent chaos.
AB  - The critical relations for statistical properties on saddle-node bifurcations are
      shown to display undulating fine structure, in addition to their known smooth
      dependence on the control parameter. A piecewise linear map with the type-I
      intermittency is studied and a log-periodic dependence is numerically obtained
      for the average time between laminar events, the Lyapunov exponent, and attractor
      moments. The origin of the oscillations is built in the natural probabilistic
      measure of the map and can be traced back to the existence of logarithmically
      distributed discrete values of the control parameter giving Markov partition.
      Reinjection and noise effect dependences are discussed and indications are given
      on how the oscillations are potentially applicable to complement predictions made
      with the usual critical exponents, taken from data in critical phenomena.

PMID- 15245012
TI  - Fourier law in the alternate-mass hard-core potential chain.
AB  - We study energy transport in a one-dimensional model of elastically colliding
      particles with alternate masses m and M. In order to prevent total momentum
      conservation, we confine particles with mass M inside a cell of finite size. We
      provide convincing numerical evidence for the validity of Fourier law of heat
      conduction in spite of the lack of exponential dynamical instability. Comparison
      with previous results on similar models shows the relevance of the role played by
      total momentum conservation.

PMID- 15245013
TI  - Standing-wave oscillations in binary mixture convection: from the onset via
      symmetry breaking to period doubling into chaos.
AB  - Oscillatory solution branches of the hydrodynamic field equations describing
      convection in the form of a standing wave (SW) in binary fluid mixtures heated
      from below are determined completely for several negative Soret coefficients psi.
      Galerkin as well as finite-difference simulations were used. They were augmented
      by simple control methods to obtain also unstable SW states. For sufficiently
      negative psi, unstable SWs bifurcate subcritically out of the quiescent
      conductive state. They become stable via a saddle-node bifurcation when lateral
      phase pinning is exerted. Eventually their invariance under timeshift by half a
      period combined with reflection at midheight of the fluid layer gets broken.
      Thereafter, they terminate by undergoing a period-doubling cascade into chaos.

PMID- 15245014
TI  - Patterns in melting snow and vapor deposited layers.
AB  - We have observed a natural periodic pattern occurring in partially melted snow
      lying on the ground under certain atmospheric conditions. We explain this
      phenomenon quantitatively by considering heat flow through this layer coexisting
      in two phases (snow and water). Our model equations exhibit a range of patterns
      depending on the average density of snow. Strikingly similar patterns have been
      observed by Plass and co-workers in monolayer depositions of Pb on heated PbCu
      substrates. We argue that the physics of the two phenomena, differing in length
      scales by 7 orders of magnitude, is similar.

PMID- 15245015
TI  - Fluid invasion in porous media: viscous gradient percolation.
AB  - We suggest that the dynamics of stable viscous invasion fronts in porous media
      depends on the volume capacitance of the media. At high volume capacitance, our
      network simulations provide numerical evidence of a scaling relation between the
      front width and its velocity. In the low volume capacitance regime, we derive a
      new effective scaling supported by network simulations and that is in agreement
      with previous experiments on imbibition in paper and collections of glass beads.

PMID- 15245017
TI  - Excitation of localized rotating waves in plasma density cavities by scattering
      of fast magnetosonic waves.
AB  - An analytic description of electromagnetic waves in an inhomogeneous plasma is
      applied to investigate excitation of localized rotating waves below the lower
      hybrid frequency through scattering of fast magnetosonic waves on a density
      cavity. The magnetosonic wave is focused to left-handed rotating oscillations. We
      find the amplitude of the localized oscillations, resonance frequencies, and the
      width of the resonances. The theory is relevant for the lower hybrid solitary
      structures observed in space plasmas and is shown to be consistent with
      observations by the Freja satellite.

PMID- 15245016
TI  - Soliton synchrotron afterglow in a laser plasma.
AB  - Coherent synchrotron radiation can be emitted by relativistic electromagnetic
      subcycle solitons dwelling in a low-temperature collisionless plasma. Using three
      dimensional particle-in-cell simulations we show that solitons, left in a wake of
      a relativistically intense short circularly polarized laser pulse in the plasma,
      emit spiral electromagnetic wave, as a result of charge density oscillations in
      the wall of the soliton cavity. This high-frequency afterglow persists for tens
      of Langmuir periods.

PMID- 15244995
TI  - Measurement of time-dependent CP asymmetries in B0-->D(*)+/-pi-/+ decays and
      constraints on sin(2beta+gamma).
AB  - We present a measurement of CP-violating asymmetries in fully reconstructed B0-
      >D(*)+/-pi-/+ decays in approximately 88 x 10(6) upsilon(4S)-->BBmacr; decays
      collected with the BABAR detector at the PEP-II asymmetric-energy B factory at
      SLAC. From a time-dependent maximum-likelihood fit we obtain the following for
      the CP-violating parameters: a=-0.022+/-0.038 (stat)+/-0.020 (syst), a*=-0.068+/
      0.038 (stat)+/-0.020 (syst), c(lep)=+0.025+/-0.068 (stat)+/-0.033 (syst), and
      c*(lep)=+0.031+/-0.070 (stat)+/-0.033 (syst). Using other measurements and
      theoretical assumptions we interpret the results in terms of the angles of the
      Cabibbo-Kobayashi-Maskawa unitarity triangle, and find |sin((2beta+gamma)|>0.69
      at 68% confidence level. We exclude the hypothesis of no CP violation
      [sin(2beta+gamma)=0] at 83% confidence level.

PMID- 15244996
TI  - Measurement of time-dependent CP asymmetries and constraints on sin(2beta+gamma)
      with partial reconstruction of B0-->D*-/+pi+/- decays.
AB  - We present a measurement of time-dependent CP-violating asymmetries in decays of
      neutral B mesons to the final states D(*-/+)pi(+/-), using approximately 82x10(6)
      BBmacr; events recorded by the BABAR experiment at the PEP-II e(+)e(-) storage
      ring. Events containing these decays are selected with a partial reconstruction
      technique, in which only the high-momentum pi(+/-) from the B decay and the low
      momentum pi(-/+) from the D(*-/+) decay are used. We measure the amplitude of the
      asymmetry to be -0.063+/-0.024(stat)+/-0.014(syst) and compute bounds on
      |sin((2beta+gamma)|.

PMID- 15245018
TI  - Instability versus equilibrium propagation of a laser beam in plasma.
AB  - We obtain, for the first time, an analytic theory of the forward stimulated
      Brillouin scattering instability of a spatially and temporally incoherent laser
      beam that controls the transition between statistical equilibrium and
      nonequilibrium (unstable) self-focusing regimes of beam propagation. The
      stability boundary may be used as a comprehensive guide for inertial confinement
      fusion designs. Well into the stable regime, an analytic expression for the
      angular diffusion coefficient is obtained, which provides an essential correction
      to a geometric optic approximation for beam propagation.

PMID- 15245020
TI  - Confinement of pure-electron plasmas in a toroidal magnetic-surface
      configuration.
AB  - A pure-electron plasma has been confined in a toroidal magnetic-surface
      configuration for as long as classical diffusion time due to neutral collisions.
      By controlling the potential of the internal conductor, long-term stable
      confinement of electrons has been achieved in a toroidal geometry.

PMID- 15245019
TI  - Shock melting of a two-dimensional complex (dusty) plasma.
AB  - Shock waves with a linear front were experimentally studied in a monolayer
      hexagonal Yukawa lattice which was formed from charged monodisperse plastic
      microspheres and levitated in the sheath of a radio-frequency discharge. It was
      found that the shock can cause phase transitions from a crystalline to gaslike
      and liquidlike states. Melting occurred in two stages. First, the lattice was
      compressed in the direction of shock propagation and second, the particle
      velocities were randomized a few lattice lines downstream. The Mach number of the
      shock reached 2.7.

PMID- 15245021
TI  - Interfacial friction of thin 3He slabs in the Knudsen limit.
AB  - A high precision torsional oscillator has been used to study 3He films of
      thickness from 100 to 350 nm, in the temperature range 5<T<200 mK. This thickness
      is much smaller than the viscous penetration depth, and also much smaller than
      the low temperature inelastic mean-free path of 3He quasiparticles. Such films
      are observed to decouple from the motion of the oscillator below 60 mK. We
      interpret the frequency shift and dissipation data in terms of an interfacial
      friction model.

PMID- 15245022
TI  - Crystallization of micelles at chemically terminated interfaces.
AB  - In aqueous solutions and for high concentrations triblock copolymers are known to
      aggregate. As a critical volume fraction of micelles is reached they crystallize.
      We report on grazing incident small angle neutron scattering as an experimental
      tool to investigate the crystallization of spherical polymer micelles in the
      immediate vicinity of a flat solid interface. We find for an attractive surface
      potential a face centered close packed structure with a random orientation
      perpendicular to the normal of the interface. For a repulsive potential
      crystallization is suppressed.

PMID- 15245023
TI  - Continuous depinning transition with an unusual hysteresis effect.
AB  - We identify a strange hysteresis which occurs in models of the depinning
      transition with both elastic and transient overshoot stresses. This hysteresis
      occurs generically despite the fact that the phase transition is still second
      order. We calculate the size of the hysteresis gap exactly in a large class of
      models. Because it is caused by irrelevant perturbations, the hysteresis does not
      show up in the field theory of the continuum limit. But since it is a real
      phenomenon it may be a cause for the hysteresis observed in natural depinning. We
      therefore discuss its experimental and numerical signatures which include
      microscopic nucleation.

PMID- 15245024
TI  - Long-time relaxation dynamics of langmuir films of a glass-forming polymer:
      evidence of glasslike dynamics in two dimensions.
AB  - We have carried out an experimental study on the mechanical relaxation of
      Langmuir films of a glass-forming polymer, poly-(4-hydroxystyrene), a good
      example of a two-dimensional system made of condensed polymer coils (at poor
      solvent conditions). This study allows us to explore the response functions of
      the film and the temperature and density dependencies of the relaxation time. The
      dynamical properties show glasslike features (non-Debye mechanical response and
      non-Arrhenius relaxation times) reconcilable within the frame of the mode
      coupling model.

PMID- 15245025
TI  - Stable fourfold configurations for small vacancy clusters in silicon from ab
      initio calculations.
AB  - Using density-functional-theory calculations, we have identified new stable
      configurations for tri-, tetra-, and pentavacancies in silicon. These new
      configurations consist of combinations of a ring hexavacancy with three, two, or
      one interstitial atoms, respectively, such that all atoms remain fourfold. As a
      result, their formation energies are lower by 0.6, 1.0, and 0.6 eV, respectively,
      than the "part of a hexagonal ring" configurations, believed until now to be the
      lowest-energy states.

PMID- 15245026
TI  - Optimal bounds on the trapping constant and permeability of porous media.
AB  - We derive exact expressions for so-called "void" bounds on the trapping constant
      gamma and fluid permeability k for coated-sphere and coated-cylinder models of
      porous media. We find that in some cases the bounds are optimal. In these
      instances, exact expressions are obtained for the relevant length scale that
      arises in the void bounds, which depends on a two-point correlation function that
      characterizes the porous medium. This is the first time that model
      microstructures have been found that exactly realize bounds on either the
      trapping constant or fluid permeability.

PMID- 15245027
TI  - Unusually dense crystal packings of ellipsoids.
AB  - In this Letter, we report on the densest-known packings of congruent ellipsoids.
      The family of new packings consists of crystal arrangements of spheroids with a
      wide range of aspect ratios, and with density phi always surpassing that of the
      densest Bravais lattice packing phi approximately equal to 0.7405. A remarkable
      maximum density of phi approximately equal to 0.7707 is achieved for maximal
      aspect ratios larger than sqrt[3], when each ellipsoid has 14 touching neighbors.
      Our results are directly relevant to understanding the equilibrium behavior of
      systems of hard ellipsoids, and, in particular, the solid and glassy phases.

PMID- 15245028
TI  - Structural relaxation in liquid water by inelastic UV scattering.
AB  - Using the novel synchrotron radiation based inelastic ultraviolet scattering
      technique, the dynamic structure factor of normal and supercooled liquid water
      has been measured at a momentum transfer Q approximately equal to 0.1 nm(-1), in
      the temperature range 260-340 K. The structural (alpha) relaxation has been
      observed in the supercooled temperature region (T< or =273 K), where the inverse
      relaxation time matches the frequency of the probed sound modes. The T dependence
      of the relaxation time shows a diverging behavior with a critical temperature T
      approximately equal to 220 K. These results provide a unique experimental
      opportunity to frame the dynamics of water in the mode-coupling theory.

PMID- 15245029
TI  - Kinking nonlinear elastic solids, nanoindentations, and geology.
AB  - The physical mechanism responsible for nonlinear elastic, hysteretic, and
      discrete memory response of nonlinear mesoscopic elastic solids has to date not
      been identified. We show, by nanoindenting mica single crystals, that this
      response is most likely due to the formation of dissipative and fully reversible,
      dislocation-based kink bands. We further claim that solids with high c/a ratios,
      which per force are plastically anisotropic, should deform by kinking, provided
      they do not twin. These kinking nonlinear elastic solids include layered ternary
      carbides, nitrides, oxides, and semiconductors, graphite, and the layered phases,
      such as mica, present in nonlinear mesoscopic elastic solids.

PMID- 15245030
TI  - Homogeneous crystallization of poly(ethylene oxide) confined to droplets: the
      dependence of the crystal nucleation rate on length scale and temperature.
AB  - We present a study of homogeneous nucleation in polymer crystallization. Crystal
      nucleation is observed within discrete droplets of poly(ethylene oxide) that are
      formed by the dewetting of a thin film. The samples provide an ensemble of
      impurity-free droplets, with length scales that can easily be measured. Droplet
      crystallization is found in two distinct temperature regimes corresponding to
      homogeneous and heterogeneous nucleation. Here we focus on homogeneous nucleation
      and show that the nucleation rate scales with the volume of the crystallizable
      domain, indicating that we are observing homogeneous nucleation in the bulk of
      the droplets. In addition, the dependence of the nucleation rate on temperature
      is consistent with classical nucleation theory.

PMID- 15245031
TI  - Phase diagram of water from computer simulation.
AB  - The phase diagram of water as obtained from computer simulations is presented for
      the first time for two of the most popular models of water, TIP4P and SPC/E. This
      Letter shows that the prediction of the phase diagram is an extremely stringent
      test for any water potential function, and that it may be useful in developing
      improved potentials. The TIP4P model provides a qualitatively correct description
      of the phase diagram, unlike the SPC/E model which fails in this purpose. New
      behavior not yet observed experimentally is predicted by the simulations: the
      existence of metastable reentrant behavior in the melting curves of the low
      density ices (I,III,V) such that it could be possible to transform them into
      amorphous phases by adequate changes in pressure.

PMID- 15245032
TI  - Reliable first-principles alloy thermodynamics via truncated cluster expansions.
AB  - In alloys cluster expansions (CE) are increasingly used to combine first
      principles electronic-structure calculations and Monte Carlo methods to predict
      thermodynamic properties. As a basis-set expansion in terms of lattice
      geometrical clusters and effective cluster interactions, the CE is exact if
      infinite, but is tractable only if truncated. Yet until now a truncation
      procedure was not well defined and did not guarantee a reliable truncated CE. We
      present an optimal truncation procedure for CE basis sets that provides reliable
      thermodynamics. We then exemplify its importance in Ni3V, where the CE has failed
      unpredictably, and now show agreement to a range of measured values, predict new
      low-energy structures, and explain the cause of previous failures.

PMID- 15245033
TI  - Quantitative phase diagrams of branching and annihilating random walks.
AB  - We demonstrate the full power of nonperturbative renormalization group methods
      for nonequilibrium situations by calculating the quantitative phase diagrams of
      simple branching and annihilating random walks and checking these results against
      careful numerical simulations. Specifically, we show, for the [see text] case,
      that an absorbing phase transition exists in dimensions d=1 to 6 and argue that
      mean-field theory is restored not in d=3, as suggested by previous analyses, but
      only in the limit d--> infinity.

PMID- 15245034
TI  - Spatially heterogeneous dynamics and dynamic facilitation in a model of viscous
      silica.
AB  - We perform molecular dynamics simulations to study the structural relaxation
      dynamics of a model of viscous silica, the prototype of a strong glass former. We
      find that the melt dynamics are spatially heterogeneous regardless of whether the
      bulk relaxation is non-Arrhenius or Arrhenius, and cannot be understood as a
      statistical bondbreaking process. Further, we show that stringlike motion is
      suppressed by the covalent bondings, yet high particle mobility propagates
      continuously, supporting the concept of dynamic facilitation emphasized in recent
      theoretical work.

PMID- 15245035
TI  - Influence of step-edge barriers on the morphological relaxation of nanoscale
      ripples on crystal surfaces.
AB  - We show that the decay of sinusoidal ripples on crystal surfaces, where mass
      transport is limited by the attachment and detachment of atoms at the step edges,
      is remarkably different from the decay behavior that has been reported until now.
      Unlike the decreasing or at most constant rate of amplitude decay of sinusoidal
      profiles observed in earlier work, we find that the decay rate increases with
      decreasing amplitude in this kinetic regime. The rate of shape invariant
      amplitude relaxation is shown to be inversely proportional to both the square of
      the wavelength and the current amplitude. We have also carried out numerical
      simulations of the relaxation of realistic sputter ripples.

PMID- 15245036
TI  - Evidence for power-law dominated noise in vacuum deposited CaF2.
AB  - We have studied the surface roughness of CaF2 vacuum deposited on glass using
      atomic force microscopy for film coverages spanning an order of magnitude. We
      find the roughness exponent alpha=0.88+/-0.03, the growth exponent beta=0.75+/
      0.03, and the dynamic exponent z=alpha/beta=1.17+/-0.06. Multifractality is also
      present, along with power-law behavior in the nearest neighbor height difference
      probability distribution. The results indicate noise dominated by a power-law
      distribution with exponent micro+1 approximately 4.6.

PMID- 15245037
TI  - Ordering of a thin lubricant film due to sliding.
AB  - A thin lubricant film confined between two substrates in moving contact is
      studied using Langevin molecular dynamics with the coordinate- and velocity
      dependent damping coefficient. It is shown that an optimal choice of the
      interaction within the lubricant can lead to minimal kinetic friction as well as
      to low critical velocity of the stick-slip to smooth-sliding transition. The
      strength of this interaction should be high enough (relative to the strength of
      the interaction of lubricant atoms with the substrates) so that the lubricant
      remains in a solid state during sliding. At the same time, the strength of the
      interaction should not be too high, in order to allow annealing of defects in the
      lubricant at slips.

PMID- 15245038
TI  - Revisiting elastic interactions between steps on vicinal surfaces: the buried
      dipole model.
AB  - We expose a new analytical method for computing elastic displacements and
      interactions due to steps on vicinal surfaces. The model of a "buried dipole"
      allows us to take into account the specific geometry of the step while performing
      anisotropic linear elasticity calculations. The displacements found show a
      remarkable agreement with molecular dynamics simulations for Cu and Pt (001) and
      (111) vicinals. The interaction energy between steps strongly depends on the
      dipole direction.

PMID- 15245039
TI  - Spectral function of the one-dimensional Hubbard model away from half filling.
AB  - We calculate the photoemission spectral function of the one-dimensional Hubbard
      model away from half filling using the dynamical density-matrix renormalization
      group method. An approach for calculating momentum-dependent quantities in finite
      open chains is presented. Comparison with exact Bethe ansatz results demonstrates
      the unprecedented accuracy of our method. Our results show that the photoemission
      spectrum of the quasi-one-dimensional conductor TTF-TCNQ provides evidence for
      spin-charge separation on the scale of the conduction bandwidth.

PMID- 15245040
TI  - Cavity polaritons in InGaN microcavities at room temperature.
AB  - Cavity polaritons are observed in InGaN quantum well (QW) microcavities at room
      temperature. High-quality microcavities are fabricated by the wafer-bonding of
      InGaN QW layers and dielectric distributed Bragg reflectors. The anticrossing
      behavior of strong exciton-photon coupling is confirmed by vacuum-field Rabi
      splitting obtained from reflection measurements. This strong coupling is also
      enhanced by increasing the integrated oscillator strength coupled to the cavity
      mode. The oscillator strength of InGaN QW excitons is 1 order of magnitude larger
      than that of GaAs QW excitons.

PMID- 15245041
TI  - Experimental separation of Rashba and Dresselhaus spin splittings in
      semiconductor quantum wells.
AB  - The relative strengths of Rashba and Dresselhaus terms describing the spin-orbit
      coupling in semiconductor quantum well (QW) structures are extracted from
      photocurrent measurements on n-type InAs QWs containing a two-dimensional
      electron gas (2DEG). This novel technique makes use of the angular distribution
      of the spin-galvanic effect at certain directions of spin orientation in the
      plane of a QW. The ratio of the relevant Rashba and Dresselhaus coefficients can
      be deduced directly from experiment and does not relay on theoretically obtained
      quantities. Thus our experiments open a new way to determine the different
      contributions to spin-orbit coupling.

PMID- 15245042
TI  - Fano resonance for Anderson impurity systems.
AB  - We present a general theory for the Fano resonance in Anderson impurity systems.
      It is shown that the broadening of the impurity level leads to an additional and
      important contribution to the Fano resonance around the Fermi surface, especially
      in the mixed valence regime. This contribution results from the interference
      between the Kondo resonance and the broadened impurity level. Being applied to
      the scanning tunneling microscopic experiments, we find that our theory gives a
      consistent and quantitative account for the Fano resonance line shapes for both
      Co and Ti impurities on Au or Ag surfaces. The Ti systems are found to be in the
      mixed valence regime.

PMID- 15245043
TI  - Resonant spin Hall conductance in two-dimensional electron systems with a Rashba
      interaction in a perpendicular magnetic field.
AB  - We study transport properties of a two-dimensional electron system with Rashba
      spin-orbit coupling in a perpendicular magnetic field. The spin-orbit coupling
      competes with Zeeman splitting to introduce additional degeneracies between
      different Landau levels at certain magnetic fields. This degeneracy, if occurring
      at the Fermi level, gives rise to a resonant spin Hall conductance, whose height
      is divergent as 1/T and whose weight is divergent as -ln(T at low temperatures.
      The Hall conductance is unaffected by the Rashba coupling.

PMID- 15245044
TI  - Detection of a Landau band-coupling-induced rearrangement of the Hofstadter
      butterfly.
AB  - The spectrum of 2D electrons subjected to a weak 2D potential and a perpendicular
      magnetic field is composed of Landau bands with a fractal internal pattern of
      subbands and minigaps referred to as Hofstadter's butterfly. The Hall conductance
      may serve as a spectroscopic tool as each filled subband contributes a specific
      quantized value. Advances in sample fabrication now finally offer access to the
      regime away from the limiting case of a very weak potential. Complex behavior of
      the Hall conductance is observed and assigned to Landau band-coupling-induced
      rearrangements within the butterfly.

PMID- 15245045
TI  - Violation of the electric-dipole selection rules in indirect multiphoton
      excitation of image-potential states on Ag(100).
AB  - Photoemission from image potential states on Ag(100) is investigated using angle
      resolved multiphoton photoemission induced by 150 fs laser pulses. For the first
      time we demonstrate that image potential states populated by indirect transitions
      can be observed with light polarized parallel to the plane of incidence and light
      polarized normal to the plane of incidence. The latter is a process normally
      forbidden by the dipole transition selection rules. These findings are related to
      the creation of a hot-electron population whose properties largely remains to be
      understood.

PMID- 15245046
TI  - Nuclear-spin-induced oscillatory current in spin-blockaded quantum dots.
AB  - We show experimentally that electron transport through GaAs-based double quantum
      dots can be affected by ambient nuclear spin states in a certain regime where
      transport is blocked in the absence of electron spin flip. Current through the
      dots oscillates in time with a period up to 200 s depending on magnetic field.
      Oscillation is quenched by application of a continuous wave ac magnetic field
      which can induce nuclear magnetic resonance in 71Ga or 69Ga. A possible mechanism
      for dynamically polarizing the nuclear spins is proposed.

PMID- 15245047
TI  - Possible observation of phase coexistence of the nu=1/3 fractional quantum hall
      liquid and a solid.
AB  - We have measured the magnetoresistance of a very low density and extremely high
      quality two-dimensional hole system. With increasing magnetic field applied
      perpendicularly to the sample we observe the sequence of insulating, nu=1/3
      fractional quantum Hall liquid, and insulating phases. In both of the insulating
      phases in the vicinity of the nu=1/3 filling the magnetoresistance has an
      unexpected oscillatory behavior with the magnetic field. These oscillations are
      not of the Shubnikov-de Haas type and cannot be explained by spin effects. They
      are most likely the consequence of the formation of a new electronic phase which
      is intermediate between the correlated Hall liquid and a disorder pinned solid.

PMID- 15245048
TI  - Mesoscopic transport in chemically doped carbon nanotubes.
AB  - Electronic quantum transport is investigated in boron- and nitrogen-doped carbon
      nanotubes using tight-binding methods correlated to ab initio calculations. The
      present technique accurately accounts for both effects of dopants, namely, charge
      transfer and elastic scattering. Generic transport properties such as conduction
      mechanisms, mean-free paths, and conductance scalings are derived for various
      concentration of randomly distributed boron and nitrogen dopants. Our
      calculations allow direct comparison with experiments and demonstrate that a
      small amount of dopants (<0.5%) can drastically modify the electronic transport
      properties of the tube, which is certainly a key effect feature for envisioning
      nanoelectronics.

PMID- 15245049
TI  - Novel phase separation and spin dynamics of lightly doped La2-xSr2CuO4 probed by
      La-nuclear quadrupole resonance.
AB  - We report novel magnetic properties in the slightly hole-doped Mott-insulator
      La(2-x)SrxCuO4 via the La-nuclear quadrupole resonance (NQR) measurements. At
      x=0.018, the antiferromagnetic (AFM) La-NQR spectrum affected by internal fields
      comes out as the temperature decreases below T(N) approximately 150 K, whereas
      the nonmagnetic one persists to be observed down to a temperature T(f)
      approximately 20 K at which the nuclear-relaxation rate has a pronounced peak.
      This demonstrates that the phase separation of nonmagnetic and AFM phases occurs
      between T(f) and T(N). The novel phase separation is suggested as due to the
      partial destruction of the AFM phase caused by mobile holes via the formation of
      an extended spin-singlet state between Cu-derived spins and hole spins.

PMID- 15245050
TI  - Lattice theory for low energy fermions at nonzero chemical potential.
AB  - We construct a lattice theory describing a system of interacting nonrelativistic
      spin s=1/2 fermions at nonzero chemical potential. The theory is applicable
      whenever the interparticle separation is large compared to the range of the two
      body potential and does not suffer from a sign problem. In particular, the theory
      could be useful in studying the thermodynamic limit of fermion systems for which
      the scattering length is much larger than the interparticle spacing, with
      applications to realistic atomic systems and dilute neutron gases.

PMID- 15245051
TI  - Electron transport through YBa2Cu3O7-delta grain boundary interfaces between 4.2
      and 300 K.
AB  - The current-induced dissipation in YBa(2)Cu(3)O(7-delta) grain boundary tunnel
      junctions has been measured between 4.2 and 300 K. It is found that the
      resistance of 45 degrees (100)/(110) junctions decreases linearly by a factor of
      4 when their temperature is increased from 100 to 300 K. At the superconducting
      transition temperature T(c) the grain boundary resistance of the normal state and
      of the superconducting state extrapolates to the same value.

PMID- 15245052
TI  - Growth of a vortex polycrystal in type II superconductors.
AB  - We discuss the formation of a vortex polycrystal in type II superconductors from
      the competition between pinning and elastic forces. We compute the elastic energy
      of a deformed grain boundary, which is strongly nonlocal, and obtain the
      depinning stress for weak and strong pinning. Our estimates for the grain size
      dependence on the magnetic field strength are in good agreement with previous
      experiments on NbMo. Finally, we discuss the effect of thermal noise on grain
      growth.

PMID- 15245053
TI  - Half-integer Shapiro steps at the 0-pi crossover of a ferromagnetic Josephson
      junction.
AB  - We investigate the current-phase relation of S/F/S junctions near the crossover
      between the 0 and the pi ground states. We use Nb/CuNi/Nb junctions where this
      crossover is driven both by thickness and temperature. For a certain thickness a
      nonzero minimum of critical current is observed at the crossover temperature. We
      analyze this residual supercurrent by applying a high frequency excitation and
      observe the formation of half-integer Shapiro steps. We attribute these
      fractional steps to a doubling of the Josephson frequency due to a sin((2phi)
      current-phase relation. This phase dependence is explained by the splitting of
      the energy levels in the ferromagnetic exchange field.

PMID- 15245054
TI  - Manifestation of the magnetic resonance mode in the nodal quasiparticle lifetime
      of the superconducting cuprates.
AB  - Studying the nodal quasiparticles in superconducting cuprates by photoemission
      with highly improved momentum resolution, we show that a new "kink" feature in
      the scattering rate is a key to uncover the nature of electron correlations in
      these compounds. Our data provide evidence that the main doping independent
      contribution to the scattering can be well understood in terms of the
      conventional Fermi liquid model, while the additional doping dependent
      contribution has a magnetic origin. This sheds doubt on applicability of a phonon
      mediated pairing mechanism to high-temperature superconductors.

PMID- 15245055
TI  - Muon spin relaxation measurements of NaxCoO2.yH2O.
AB  - Using the transverse field muon spin relaxation technique, we measure the
      temperature dependence of the magnetic field penetration depth lambda, in the
      NaxCoO2.yH(2)O system. We find that lambda, which is determined by the superfluid
      density n(s) and the effective mass m*, is very small and on the edge of the TF
      microSR sensitivity. Nevertheless, the results indicate that this system obeys
      the Uemura relation. By comparing lambda with the normal state electron density,
      we conclude that m* of the superconductivity carrier is 70 times larger than the
      mass of bare electrons. Finally, the order parameter in this system cannot be
      described by a complete gap over the entire Fermi surface.

PMID- 15245056
TI  - Ferroelectricity and giant magnetocapacitance in perovskite rare-earth
      manganites.
AB  - The relationships among magnetism, lattice modulation, and dielectric properties
      have been investigated for RMnO3 (R=Eu, Gd, Tb, and Dy). These compounds show a
      transition to an incommensurate lattice structure below their Neel temperature,
      and subsequently undergo an incommensurate-commensurate (IC-C) phase transition.
      For TbMnO3 and DyMnO3 it was found that the IC-C transition is accompanied by a
      ferroelectric transition, associated with a lattice modulation in the C phase.
      DyMnO3 shows a gigantic magnetocapacitance with a change of dielectric constant
      up to Deltaepsilon/epsilon approximately 500%.

PMID- 15245057
TI  - Origin of higher order magnetic exchange: evidence for local dimer exchange
      striction in CsMn0.28Mg0.72Br3 probed by inelastic neutron scattering.
AB  - The origin of higher-order exchange interactions in localized S-state systems has
      been the subject of intensive investigations in the past. In particular, it has
      been suggested that a biquadratic exchange term may arise from the magnetoelastic
      energy. Here we report on the pressure and temperature dependence of the
      excitation spectra of magnetic Mn2+ dimers in CsMn0.28Mg0.72Br3 probed by
      inelastic neutron scattering. Biquadratic exchange and a strong distance
      dependence of the bilinear exchange are observed. It is shown that the mechanism
      of local exchange striction may explain the occurrence of biquadratic exchange in
      accordance with the elastic properties of the compound.

PMID- 15245058
TI  - Phase transitions in a disordered system in and out of equilibrium.
AB  - The equilibrium and nonequilibrium disorder-induced phase transitions are
      compared in the random-field Ising model. We identify in the demagnetized state
      the correct nonequilibrium hysteretic counterpart of the T=0 ground state, and
      present evidence of universality. Numerical simulations in d=3 indicate that
      exponents and scaling functions coincide, while the location of the critical
      point differs, as corroborated by exact results for the Bethe lattice. These
      results are of relevance for optimization, and for the generic question of
      universality in the presence of disorder.

PMID- 15245059
TI  - Surface roughness induced extrinsic damping in thin magnetic films.
AB  - The ferromagnetic relaxation caused by the surface roughness induced 2-magnon
      scattering is investigated. Approximate analytical solution predicts
      nonexponential decay of the uniform precession excitations of the form exp[
      |t/tau3/2|3/2]. This behavior as well as the dependence of the decay time
      tau(3/2) on roughness parameters are confirmed by micromagnetic simulations.

PMID- 15245060
TI  - Displacement profile of charge density waves and domain walls at critical
      depinning.
AB  - The influence of a strong surface potential on the critical depinning of an
      elastic system driven in a random medium is considered. If the surface potential
      prevents depinning completely the curvature C of the displacement profile
      exhibits at zero temperature a pronounced rhombic hysteresis curve of width 2f(c)
      with the bulk depinning threshold f(c). The hysteresis disappears at nonzero
      temperatures if the driving force is changed adiabatically. If the surface depins
      by the applied force or thermal creep, C is reduced with increasing velocity. The
      results apply, e.g., to driven magnetic domain walls, fluxline lattices, and
      charge-density waves.

PMID- 15245061
TI  - Unusual oscillation in tunneling magnetoresistance near a quantum critical point
      in Sr3Ru2O7.
AB  - We performed single-electron tunneling measurements on bilayer ruthenate
      Sr3Ru2O7. We observe an unusual oscillation in tunneling magnetoresistance near
      the metamagnetic quantum phase transition. The characteristic features of this
      oscillation suggest that it is unrelated to traditional quantum oscillations
      caused by orbit quantization. In addition, tunneling spectra are found to change
      sharply in the low bias voltage range of V<2 mV near the transition field. These
      observations reveal that the Fermi surface of Sr3Ru2O7 changes in a surprising
      way as the system undergoes strong critical fluctuations.

PMID- 15245062
TI  - Interchange of the quantum states of confined excitons caused by radiative
      corrections in CuCl films.
AB  - The energy states of a particle confined in a narrow space are discrete and lined
      up in the order of n=1,2,3,.... However, if the particle interacts with a
      radiation field, modification of the energy, referred to radiative correction,
      will occur and quantum states are expected to interchange. We investigated the
      center-of-mass confinement of excitons in CuCl films by a new method based on
      "nondegenerate two-photon excitation scattering." The energies of confined
      excitons in a 19.3 nm thick film are found to be lined up in the order of
      n=1,3,5, because the radiative correction is very weak. On the other hand, in a
      35.3 nm thick film, in which the radiative correction becomes large, the energies
      of quantum states are ordered n=2,3,4,1,5,7. This interchange is confirmed by
      comparing the calculated scattering spectra, in which radiative correction is
      taken into account, with the measured ones.

PMID- 15245063
TI  - Scaling of excitons in carbon nanotubes.
AB  - Light emission from carbon nanotubes is expected to be dominated by excitonic
      recombination. Here we calculate the properties of excitons in nanotubes embedded
      in a dielectric, for a wide range of tube radii and dielectric environments. We
      find that simple scaling relationships give a good description of the binding
      energy, exciton size, and oscillator strength.

PMID- 15245064
TI  - Experimental demonstration of entanglement-enhanced classical communication over
      a quantum channel with correlated noise.
AB  - We present an experiment demonstrating the entanglement enhanced capacity of a
      quantum channel with correlated noise, modeled by a fiber optic link exhibiting
      fluctuating birefringence. In this setting, introducing entanglement between two
      photons is required to maximize the amount of information that can be encoded
      into their joint polarization degree of freedom. We demonstrated this effect
      using a fiber-coupled source of entangled photon pairs based on spontaneous
      parametric down-conversion, and a linear-optics Bell state measurement. The
      obtained experimental classical capacity with entangled states is equal to 0.82+/
      0.04 per a photon pair, and it exceeds approximately 2.5 times the theoretical
      upper limit when no quantum correlations are allowed.

PMID- 15245065
TI  - Anomalous hydrodynamic interaction in a quasi-two-dimensional suspension.
AB  - We study the correlated Brownian motion of micron-sized particles suspended in
      water and confined between two plates. The hydrodynamic interaction between the
      particles exhibits three anomalies. (i) The transverse coupling is negative;
      i.e., particles exert "antidrag" on one another when moving perpendicular to
      their connecting line. (ii) The interaction decays with interparticle distance r
      as 1/r(2), faster than in unconfined suspensions but slower than near a single
      wall. (iii) At large distances, the pair interaction is independent of
      concentration within the experimental accuracy. The confined suspension thus
      provides an unusual example of long-range, yet essentially pairwise, correlations
      even at high concentration. These effects are shown to arise from the two
      dimensional dipolar form of the flow induced by single-particle motion.

PMID- 15245066
TI  - Relaxation to equilibrium can be hindered by transient dissipative structures.
AB  - Relaxation processes in a closed chemical reaction-diffusion system which can
      potentially form Turing-like patterns during the transient are investigated to
      address the question given by the title. We find that when certain conditions are
      fulfilled the relaxation process is indeed drastically hindered, once the pattern
      is formed. This slowing down is shown to be due to stepwise relaxation, where
      each plateau in the relaxation process corresponds to residence at a certain
      spatial pattern. Mechanism and universality of the phenomena are discussed.

PMID- 15245067
TI  - Jamming threshold of dry fine powders.
AB  - We report a novel experimental study on the jamming transition of dry fine
      powders with controlled attractive energy and particle size. Like in attractive
      colloids dry fine particles experience diffusion-limited clustering in the
      fluidlike regime. At the jamming threshold fractal clusters crowd in a metastable
      state at volume fractions depending on attractive energy and close to the volume
      fraction of hard nonattractive spheres at jamming. Near the phase transition the
      stress-(volume fraction) relationship can be fitted to a critical-like functional
      form for a small range of applied stresses sigma approximately (phi-phi(J))(beta)
      as measured on foams, emulsions, and colloidal systems and predicted by numerical
      simulations on hard spheres.

PMID- 15245068
TI  - Comment on "Positivity of quasilocal mass".

PMID- 15245070
TI  - Intrinsic tunneling or Joule heating?

PMID- 15245072
TI  - Complexity of random energy landscapes, glass transition, and absolute value of
      the spectral determinant of random matrices.
AB  - Finding the mean of the total number N(tot) of stationary points for N
      dimensional random energy landscapes is reduced to averaging the absolute value
      of the characteristic polynomial of the corresponding Hessian. For any finite N
      we provide the exact solution to the problem for a class of landscapes
      corresponding to the "toy model" of manifolds in a random environment. For N>>1
      our asymptotic analysis reveals a phase transition at some critical value mu(c)
      of a control parameter mu from a phase with a finite landscape complexity: N(tot)
      approximately e(N Sigma), Sigma(mu<mu(c))>0 to the phase with vanishing
      complexity: Sigma(mu>mu(c))=0. Finally, we discuss a method of dealing with the
      modulus of the spectral determinant applicable to a broad class of problems.

PMID- 15245073
TI  - Model for fluctuating inflaton coupling: sneutrino induced adiabatic
      perturbations and nonthermal leptogenesis.
AB  - We discuss a unique possibility of generating adiabatic density perturbations and
      leptogenesis from the spatial fluctuations of the inflaton decay rate. The key
      assumption is that the initial isocurvature perturbations are created in the
      right-handed sneutrino sector during inflation which is then converted into
      adiabatic perturbations when the inflaton decays. We discuss distinct imprints on
      the cosmic microwave background radiation, which can distinguish nonthermal
      versus thermal leptogenesis.

PMID- 15245074
TI  - New dark energy constraints from supernovae, microwave background, and galaxy
      clustering.
AB  - Using supernova, cosmic microwave background, and galaxy clustering data, we make
      the most accurate measurements to date of the dark energy density rho(X) as a
      function of cosmic time, constraining it in a rather model-independent way,
      assuming a flat universe. We find that Einstein's simplest scenario, where
      rho(X)(z) is constant, remains consistent with these new tight constraints and
      that a big crunch or big rip is more than 50 Gyr away for a broader class of
      models allowing such cataclysmic events. We discuss popular pitfalls and hidden
      priors.

PMID- 15245075
TI  - Discovering the Higgs bosons of minimal supersymmetry with muons and a bottom
      quark.
AB  - We investigate the prospects for the discovery at the CERN Large Hadron Collider
      (LHC) of a neutral Higgs boson produced with one bottom quark followed by Higgs
      decay into a muon pair. We work within the framework of the minimal
      supersymmetric model. The dominant physics background from the production of b
      mu(+)mu(-), j mu(+)mu(-), j=g,u,d,s,c, and bbW+W- is calculated with realistic
      acceptance cuts. Promising results are found for the CP-odd pseudoscalar (A0) and
      the heavier CP-even scalar (H0) Higgs bosons with masses up to 600 GeV. This
      discovery channel with one energetic bottom quark greatly improves the discovery
      potential of the LHC beyond the inclusive channel pp-->phi(0)-->mu(+)mu(-)+X.

PMID- 15245077
TI  - Mass of the eta b and alpha s from the nonrelativistic renormalization group.
AB  - We sum up the next-to-leading logarithmic corrections to the heavy-quarkonium
      hyperfine splitting, using the nonrelativistic renormalization group. On the
      basis of this result, we predict the mass of the eta(b) meson to be
      M(eta(b))=9421+/-11(th)+9-8(delta alpha(s)) MeV. The experimental measurement of
      M(eta(b)) with a few MeV error would be sufficient to determine alpha(s)(M(Z))
      with an accuracy of +/-0.003. For the hyperfine splitting in charmonium, the use
      of the nonrelativistic renormalization group brings the perturbative prediction
      significantly closer to the experimental figure.

PMID- 15245078
TI  - Physical nucleon properties from lattice QCD.
AB  - We investigate various resummations of the chiral expansion and fit to the
      extremely accurate lattice QCD data for the mass of the nucleon recently obtained
      by the CP-PACS group. Using a variety of finite-range regulators, we demonstrate
      a remarkably robust chiral extrapolation of the nucleon mass. The systematic
      error associated with the chiral extrapolation alone is estimated to be less than
      1%.

PMID- 15245079
TI  - Combined nuclear-molecular resonance inelastic scattering of x rays.
AB  - We report on theoretical and experimental studies of nuclear inelastic scattering
      in a molecular crystal, whose atoms experience both molecular and lattice
      vibrations. In this case scattering proceeds as combined nuclear-molecular
      resonance inelastic scattering. The lattice vibrations give rise to inelastic
      scattering around the molecular resonances with an energy dependence identical to
      that around the nuclear resonance. The incoherent nature of the scattering in the
      molecular resonances results in a proper balance of elastic and inelastic
      components, which has important implications for studies of heterogeneous
      systems.

PMID- 15245080
TI  - State selective enhanced production of excited fragments and ionic fragments of
      gaseous Si(CH3)2Cl2 and solid-state analogs following core-level excitation.
AB  - State-selective fragmentation dynamics for excited fragments and ionic fragments
      of gaseous and condensed Si(CH3)2Cl2 following Cl 2p and Si 2p core-level
      excitations have been characterized. The Cl 2p-->15a1* excitation of Si(CH3)2Cl2
      induces significant enhancement of the Cl+ desorption yield in the condensed
      phase and the Si(CH3)+2 and SiCH+3 yields in the gaseous phase. The core-to
      Rydberg excitations at both Si 2p and Cl 2p edges lead to enhanced production of
      the excited fragments. These complementary results provide deeper insight into
      the origin of state-selective fragmentation of molecules via core-level
      excitation.

PMID- 15245081
TI  - Control of Raman lasing in the nonimpulsive regime.
AB  - We explore coherent control of stimulated Raman scattering in the nonimpulsive
      regime. Optical pulse shaping of the coherent pump field leads to control over
      the stimulated Raman output. A model of the control mechanism is investigated.

PMID- 15245082
TI  - Polarization and trapping of weakly bound atoms in penning trap fields.
AB  - The ATHENA and ATRAP groups at CERN recently reported the production of weakly
      bound antihydrogen atoms in a non-neutral positron-antiproton plasma. This Letter
      derives an equation of motion for weakly bound atoms in the electric and magnetic
      fields of the plasma and trap. The atoms are polarized by the electric field and
      can be trapped radially in the edge region of the plasma where the electric field
      is maximum.

PMID- 15245083
TI  - Nonlinear dynamics of incommensurate surface layers.
AB  - We describe analytically the nonlinear dynamics of the incommensurate surface
      layer ("self-modulated" system) with a spatially periodical structure. In the
      framework of the Frenkel-Kontorova model the nonlinear excitations of the
      periodic soliton lattice, such as moving additional kinks and gap solitons, are
      investigated.

PMID- 15245084
TI  - Structure of wave functions of pseudointegrable billiards.
AB  - Wave functions of pseudointegrable plane polygonal billiards are investigated. It
      is demonstrated that they have clear structures (superscars) related with
      families of classical periodic orbits which do not disappear at large energy.

PMID- 15245085
TI  - Flow of He II due to an oscillating grid in the low-temperature limit.
AB  - The macroscopic flow properties of pure He II are probed in the limit of zero
      temperature using an oscillating grid. As the oscillation amplitude passes a
      first critical threshold, the resonant frequency starts decreasing but the flow
      remains nondissipative. Beyond a second critical amplitude, the flow undergoes a
      transition to turbulence and becomes dissipative. Nonlinearity and hysteresis
      observed between the thresholds are attributed to a boundary layer of quantized
      vortices.

PMID- 15245086
TI  - Control of spatiotemporal disorder in parametrically excited surface waves.
AB  - Interacting surface waves, parametrically excited by two commensurate
      frequencies, yield a number of nonlinear states. Near the system's bicritical
      point, a state, highly disordered in space and time, results from competition
      between nonlinear states. Experimentally, this disordered state can be rapidly
      stabilized to a variety of nonlinear states via open-loop control with a small
      amplitude third frequency excitation, whose temporal symmetry governs the
      temporal and the spatial symmetry of the selected nonlinear state. This technique
      also excites rapid switching between nonlinear states.

PMID- 15245087
TI  - Drag reduction by polymers in wall bounded turbulence.
AB  - We elucidate the mechanism of drag reduction by polymers in turbulent wall
      bounded flows: while momentum is produced at a fixed rate by the forcing, polymer
      stretching results in the suppression of momentum flux to the wall. On the basis
      of the equations of fluid mechanics we develop the phenomenology of the "maximum
      drag reduction asymptote" which is the maximum drag reduction attained by
      polymers. Based on Newtonian information only we demonstrate the existence of
      drag reduction, and with one experimental parameter we reach agreement with the
      experimental measurements.

PMID- 15245088
TI  - Growth of density inhomogeneities in a flow of wave turbulence.
AB  - We consider the flow being a superposition of random waves and describe the
      evolution of the spectrum of the passive scalar in the leading (fourth) order
      with respect to the wave amplitudes. We find that wave turbulence can produce an
      exponential growth of the passive scalar fluctuations when either both solenoidal
      and potential components are present in the flow or there are potential waves
      with the same frequencies but different wave numbers.

PMID- 15245089
TI  - Fluid pinch-off dynamics at nanometer length scales.
AB  - The breakup of a drop of inviscid fluid into two smaller drops is determined by a
      competition between surface and inertial forces. This process forms a thin
      filament of fluid with a connecting neck that shrinks to zero diameter at a
      finite time singularity. We present measurements of the electrical resistance of
      a liquid bridge of mercury as it undergoes pinch off. The electrical measurements
      allow us to probe the region of the singularity down to nanosecond times and
      nanometer lengths. Near pinch off, the resistance of the liquid bridge diverges
      as t(-2/3), as expected for inviscid flow.

PMID- 15245090
TI  - Flux conversion and evidence of relaxation in a high-beta plasma formed by high
      speed injection into a mirror confinement structure.
AB  - High-beta plasmoids can survive the violent dynamics of supersonic reflection off
      mirror structures, producing a stable high-beta field-reversed configuration
      (FRC). This shows both the robustness of FRCs and their tendency to assume a
      preferred plasma state, possibly conforming to a relaxation principle. The key
      observations are (1) approximate preservation of the magnetic helicity, (2)
      substantial conversion from toroidal to poloidal magnetic flux, (3) substantial
      toroidal flow, and (4) a high-beta quiescent final state. These results are from
      the Translation, Confinement, and Sustainment experiment where a disorganized
      plasmoid is injected at super-Alfvenic speed into a confinement chamber. After
      successive reflections from end mirrors, the plasmoid settled into a near-FRC
      state with high beta and low toroidal magnetic field. The flux conversion and
      helicity preservation are inferred by an interpretive model.

PMID- 15245091
TI  - Spatial and temporal structure of edge-localized modes.
AB  - This Letter provides information on the spatial and temporal structure of
      periodic eruptions observed in magnetically confined laboratory fusion plasmas,
      called edge-localized modes (ELMs), and highlights similarities with solar
      eruptions. Taken together, the observations presented in this Letter provide
      strong evidence for ELMs being associated with a filamentlike structure. These
      filaments are extended along a field line, are generated on a 100 micros time
      scale, erupt from the outboard side, and connect back into the plasma. Such
      structures are predicted by a theoretical model based on the "ballooning"
      instability, developed for both solar and tokamak applications.

PMID- 15245092
TI  - Measurement of Landau damping and the evolution to a BGK equilibrium.
AB  - Linear Landau damping and nonlinear wave-particle trapping oscillations are
      observed with standing plasma waves in a trapped pure electron plasma. For low
      wave amplitudes, the measured linear damping rate agrees quantitatively with
      linear Landau damping theory. At larger amplitudes, the wave initially damps at
      the Landau rate, then regrows and oscillates, approaching a steady state, as
      predicted by O'Neil in 1965 [Phys. Fluids 8, 2255 (1965)]]. This BGK equilibrium
      is observed to decay slowly due to external dissipation.

PMID- 15245093
TI  - Light-induced giant softening of network glasses observed near the mean-field
      rigidity transition.
AB  - The longitudinal acoustic (LA) mode of bulk GexSe1-x glasses is examined in
      Brillouin scattering (BS) over the 0.15<x<1/3 range using near band-gap radiation
      (lambda=647.1 nm). The LA-mode frequency (nu(LA)) softens with increasing laser
      power in an athermal and reversible manner by nearly 30% (=Delta nu(LA)/nu(LA))
      near x=x(c)=0.19(1) or mean coordination number, r(c)=2+2x(c)=2.38(2), close to
      the mean-field rigidity percolation transition (r(t)=2.40). BS is a bulk probe of
      elasticity, and photosoftening is maximized here when network stress is minimized
      near the elastic phase transition.

PMID- 15245094
TI  - Effect of low-level radiation on the low temperature acoustic behavior of a-SiO2.
AB  - We report on the mechanical behavior of an a-SiO2 84 kHz torsional oscillator
      operated between 100> or =T> or =1.0 mK. Below 10 mK we observed well
      differentiated transient responses which we attribute to the interaction with low
      level background radiation (gamma quanta and cosmic ray micro) and which can be
      modeled in terms of a change in the spring constant.

PMID- 15245095
TI  - Structural amorphous steels.
AB  - Recent advancement in bulk metallic glasses, whose properties are usually
      superior to their crystalline counterparts, has stimulated great interest in
      fabricating bulk amorphous steels. While a great deal of effort has been devoted
      to this field, the fabrication of structural amorphous steels with large cross
      sections has remained an alchemist's dream because of the limited glass-forming
      ability (GFA) of these materials. Here we report the discovery of structural
      amorphous steels that can be cast into glasses with large cross-section sizes
      using conventional drop-casting methods. These new steels showed interesting
      physical, magnetic, and mechanical properties, along with high thermal stability.
      The underlying mechanisms for the superior GFA of these materials are discussed.

PMID- 15245096
TI  - Unusual glass-forming ability of bulk amorphous alloys based on ordinary metal
      copper.
AB  - We report the unusual glass-forming ability (GFA) of a family of Cu-based alloys,
      Cu46Zr47-xAl7Yx (0<x< or =10, in at. %), and investigate the origin of this
      unique property. By an injection mold casting method, these alloys can be readily
      solidified into amorphous structures with the smallest dimension ranging from 4
      mm up to 1 cm without detectable crystallinity. Such superior GFA is found
      primarily due to the alloying effect of Y, which lowers the alloy liquidus
      temperature and brings the composition closer to a quaternary eutectic. Other
      beneficial factors including appropriate atomic-size mismatch and large negative
      heat of mixing among constituent elements are also discussed.

PMID- 15245076
TI  - Study of B+/ --> J/psi pi+/- and B+/ -->J/psi K+/- decays: measurement of the
      ratio of branching fractions and search for direct CP violation.
AB  - We study B+/ --> J/psi pi(+/-) and B+/ --> J/psi K+/- decays in a sample of about
      89 x 10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric B
      factory at SLAC. We observe a signal of 244+/-20 B+/ --> J/psi pi(+/-) events and
      determine the ratio B(B+/ --> J/psi pi(+/-))/B(B+/ --> J/psi K+/-) to be [5.37+/
      0.45(stat)+/-0.11(syst)]%. The charge asymmetries for the B+/ --> J/psi pi(+/-)
      and B+/ --> J/psi K+/- decays are determined to be A(pi)=0.123+/-0.085(stat)+/
      0.004(syst) and A(K)=0.030+/-0.015(stat)+/-0.006(syst), respectively.

PMID- 15245097
TI  - Roughening of fracture surfaces: the role of plastic deformation.
AB  - Post mortem analysis of fracture surfaces of ductile and brittle materials on the
      microm-mm and the nm scales, respectively, reveal self-affine cracks with
      anomalous scaling exponent zeta approximately 0.8 in three dimensions and zeta
      approximately 0.65 in two dimensions. Attempts to use elasticity theory to
      explain this result failed, yielding exponent zeta approximately 0.5 up to
      logarithms. We show that when the cracks propagate via plastic void formations in
      front of the tip, followed by void coalescence, the void positions are positively
      correlated to yield exponents higher than 0.5.

PMID- 15245098
TI  - Universal dynamic fragmentation in D dimensions.
AB  - A generic model is introduced for brittle fragmentation in D dimensions, and this
      model is shown to lead to a fragment-size distribution with two distinct
      components. In the small fragment-size limit a scale-invariant size distribution
      results from a crack branching-merging process. At larger sizes the distribution
      becomes exponential as a result of a Poisson process, which introduces a large
      scale cutoff. Numerical simulations are used to demonstrate the validity of the
      distribution for D=2. Data from laboratory-scale experiments and large-scale
      quarry blastings of granitic gneiss confirm its validity for D=3. In the
      experiments the nonzero grain size of rock causes deviation from the ideal model
      distribution in the small-size limit. The size of the cutoff seems to diverge at
      the minimum energy sufficient for fragmentation to occur, but the scaling
      exponent is not universal.

PMID- 15245099
TI  - Observation of ordered phases of fullerenes in carbon nanotubes.
AB  - We have assembled molecular arrays of C60 inside double-walled carbon nanotubes
      (DWNTs) with internal diameters of 11-26 A and directly observed the existence of
      different crystalline phases of C60 previously predicted theoretically. The
      structure of the encapsulated C60 crystal is defined by the internal diameter of
      the DWNT, as the molecules adjust their packing arrangement in order to maximize
      van der Waals interactions. We have also shown that fullerenes in C(60)@DWNT
      interact with the outer layer of DWNTs, as demonstrated by the efficient filling
      of DWNTs with internal diameters of less than 12 A.

PMID- 15245100
TI  - Collective nature of the boson peak and universal transboson dynamics of glasses.
AB  - Using probe molecules with resonant nuclei and nuclear inelastic scattering, we
      are able to measure the density of states exclusively for collective motions with
      a correlation length of more than approximately 20 A. Such spectra exhibit an
      excess of low-energy modes (boson peak). This peak behaves in the same way as
      that observed by conventional methods. This shows that a significant part of the
      modes constituting the boson peak is of collective character. At energies above
      the boson peak, the reduced density of states of the collective motions
      universally exhibits an exponential decrease.

PMID- 15245101
TI  - Soft lubrication.
AB  - We consider some basic principles of fluid-induced lubrication at soft
      interfaces. In particular, we quantify how a soft substrate changes the geometry
      of and the forces between surfaces sliding past each other. By considering the
      model problem of a symmetric nonconforming contact moving tangentially to a thin
      elastic layer, we determine the normal force in the small and large deflection
      limit, and show that there is an optimal combination of material and geometric
      properties which maximizes the normal force. Our results can be generalized to a
      variety of other geometries which show the same qualitative behavior. Thus, they
      are relevant in the elastohydrodynamic lubrication of soft elastic and
      poroelastic gels and shells, and in the context of biolubrication in
      cartilaginous joints.

PMID- 15245102
TI  - Unsteady crack motion and branching in a phase-field model of brittle fracture.
AB  - Crack propagation is studied numerically using a continuum phase-field approach
      to mode III brittle fracture. The results shed light on the physics that controls
      the speed of accelerating cracks and the characteristic branching instability at
      a fraction of the wave speed.

PMID- 15245103
TI  - Novel isotope effects observed in polarization echo experiments in glasses.
AB  - In recent years unexpected magnetic field effects have been observed in
      dielectric measurements on insulating glasses at very low temperatures.
      Polarization echo experiments have indicated that atomic tunneling systems are
      responsible for these effects and that the nuclear properties of the tunneling
      particles are of importance. Subsequently, it was suggested that the magnetic
      field effects are caused by tunneling systems carrying a nuclear quadrupole
      moment. Now we have studied the isotope effect in echo experiments on fully
      deuterated and ordinary glycerol clearly showing the crucial role of the nuclear
      quadrupole moments for the magnetic field effects. In addition, we have observed
      a new effect in the decay of spontaneous echoes in zero magnetic field for the
      deuterated samples which can be explained in terms of a quantum beating involving
      the quadrupole levels.

PMID- 15245104
TI  - Long-range critical wetting: observation of a critical end point.
AB  - Alkanes deposited on aqueous substrates exhibit two different types of wetting
      behavior: alternatively to the usual first-order wetting transition, a sequential
      wetting scenario of a long-range critical wetting transition preceded by a first
      order thin-thick transition may be observed. Here, we present the first
      successful experimental attempt to locate the transition point between the
      standard first-order wetting and the long-range critical wetting: a critical end
      point, observed in a mixture of pentane and hexane which is deposited on an
      aqueous solution of glucose. Furthermore, we present the first direct measurement
      of the contact angle in the intermediate wetting state (frustrated-complete
      wetting) in the sequential-wetting scenario of hexane on brine and compare to
      theoretical predictions.

PMID- 15245105
TI  - Viscosity at the dynamic crossover in o-terphenyl and salol under high pressure.
AB  - The viscosities of two prototypical glass formers, o-terphenyl and phenyl
      salicylate (salol), are shown to exhibit a change in their temperature and
      pressure dependences at a constant value of the viscosity. This is the first
      evidence of a dynamic crossover in the viscosity induced by pressure. The
      characteristic value associated with the change in dynamics is material
      dependent, but independent of temperature and pressure. These results are in
      accord with the previous finding, for other glass formers, that the dielectric
      relaxation time assumes a density-independent value at the dynamic crossover.

PMID- 15245106
TI  - Drift causes anomalous exponents in growth processes.
AB  - The effect of a drift term in the presence of fixed boundaries is studied for the
      one-dimensional Edwards-Wilkinson equation, to reveal a general mechanism that
      causes a change of exponents for a very broad class of growth processes. This
      mechanism represents a relevant perturbation and therefore is important for the
      interpretation of experimental and numerical results. In effect, the mechanism
      leads to the roughness exponent assuming the same value as the growth exponent.
      In the case of the Edwards-Wilkinson equation this implies exponents deviating
      from those expected by dimensional analysis.

PMID- 15245107
TI  - Kinetic roughening of laser deposited polymer films: crossover from single
      particle character to continuous growth.
AB  - The crossover in kinetic roughening of thin films from a particle-character
      dominated regime to continuous growth behavior has been observed in this work.
      This has been accomplished by atomic force microscopy investigations of pulsed
      laser deposited amorphous organic films with thicknesses ranging from several
      nanometers to more than 4 microm. The early-stage random-deposition-like
      processes end once a closed layer is formed, which grows without saturation on
      the characteristic length scales. In addition, the influence of oblique film
      deposition has been examined and interpreted.

PMID- 15245108
TI  - Quantitative evaluation of spatial coherence of the electron beam from low
      temperature field emitters.
AB  - By using multiwalled carbon nanotubes as an element of a nanobiprism, we
      evaluated quantitatively the coherence of electrons emitted from tungsten tips at
      room temperature and 78 K, and found an enhancement of coherence at 78 K. The
      increase of the transverse coherence length of the electron beam agreed well with
      that of the inelastic mean free path of electrons in solids, demonstrating the
      direct relationship between the coherences of the electron beam and the original
      electronic states. On the basis of this experimental fact, we comment on the
      interpretation of recent Hanbury Brown-Twiss type experiments for electrons
      reported by Kiesel et al. [Nature (London) 418, 392 (2002)]].

PMID- 15245109
TI  - Kinetic roughening of ion-sputtered Pd(001) surface: beyond the Kuramoto
      Sivashinsky model.
AB  - We investigate the kinetic roughening of Ar+ ion-sputtered Pd(001) surface both
      experimentally and theoretically. In situ real-time x-ray reflectivity and in
      situ scanning tunneling microscopy show that nanoscale adatom islands form and
      grow with increasing sputter time t. Surface roughness W(t) and lateral
      correlation length xi(t) follow the scaling laws W(t) approximately t(beta) and
      xi(t) approximately t(1/z) with the exponents beta approximately 0.20 and 1/z
      approximately 0.20, for an ion beam energy epsilon=0.5 keV, which is inconsistent
      with the prediction of the Kuramoto-Sivashinsky (KS) model. We thereby extend the
      KS model by applying the coarse-grained continuum approach of the Sigmund theory
      to the order of O(inverted Delta(4),h(2)), where h is the surface height, and
      derive a new term of the form inverted Delta(2)(inverted Delta h)(2) which plays
      a decisive role in describing the observed morphological evolution of the
      sputtered surface.

PMID- 15245110
TI  - Atomistic and lattice model of a grain boundary defaceting phase transition.
AB  - Recent calculations have shown that grain boundary (GB) stress is too small to
      stabilize finite GB facets, suggesting that the existing theory of GB defaceting
      phase transitions is incomplete. We perform molecular dynamics calculations,
      which show a reversible phase transition at approximately 400 K with a concerted
      shuffle of two atoms at the facet junction as the elementary excitation. Based on
      this excitation we formulate an appropriate lattice model, perform Monte Carlo
      simulations, and establish an analytical relationship between the elementary
      excitation energy and the transition temperature.

PMID- 15245111
TI  - Step edge sputtering yield at grazing incidence ion bombardment.
AB  - The surface morphology of Pt(111) was investigated by scanning tunneling
      microscopy after 5 keV Ar+ ion bombardment at grazing incidence in dependence of
      the ion fluence and in the temperature range between 625 and 720 K. The average
      erosion rate was found to be strongly dependent on the ion fluence and the
      substrate temperature during bombardment. This dependence is traced back to the
      variation of step concentration with temperature and fluence. We develop a simple
      model allowing us to determine separately the constant sputtering yields for
      terraces and for impact area stripes in front of ascending steps. The
      experimentally determined yield of these stripes--the step-edge sputtering yield-
      is in excellent agreement with our molecular dynamics simulations performed for
      the experimental situation.

PMID- 15245112
TI  - Dependence of quasiliquid thickness on the liquid activity: a bulk thermodynamic
      theory of the interface.
AB  - Studies of the phenomenon of quasiliquid formation span systems as diverse as
      noble gases, complex organic molecules, and metals, and span triple point
      temperatures from 25 to 933 K. We show that when viewed as a single phenomenon
      essentially all published measurements of the quasiliquid layer thickness on
      solids below the melting point can be plotted as a function of the thermodynamic
      activity. Two classes of behavior are then observed: one for molecular systems
      and one for atomic systems. We derive a dependence on activity through a grand
      canonical lattice gas calculation. This is the only such unifying theory of this
      phenomenon.

PMID- 15245113
TI  - van der Waals density functional for general geometries.
AB  - A scheme within density functional theory is proposed that provides a practical
      way to generalize to unrestricted geometries the method applied with some success
      to layered geometries [Phys. Rev. Lett. 91, 126402 (2003)]]. It includes van der
      Waals forces in a seamless fashion. By expansion to second order in a carefully
      chosen quantity contained in the long-range part of the correlation functional,
      the nonlocal correlations are expressed in terms of a density-density interaction
      formula. It contains a relatively simple parametrized kernel, with parameters
      determined by the local density and its gradient. The proposed functional is
      applied to rare gas and benzene dimers, where it is shown to give a realistic
      description.

PMID- 15245114
TI  - Fermi surface and quasiparticle dynamics of Na0.7CoO2 investigated by angle
      resolved photoemission spectroscopy.
AB  - We present the first angle-resolved photoemission study of Na0.7CoO2, the host
      material of the superconducting NaxCoO2.nH(2)O series. Our results show a hole
      type Fermi surface, a strongly renormalized quasiparticle band, a small Fermi
      velocity, and a large Hubbard U. The quasiparticle band crosses the Fermi level
      from M toward Gamma suggesting a negative sign of effective single-particle
      hopping t(eff) (about 10 meV) which is on the order of magnetic exchange coupling
      J in this system. Quasiparticles are well defined only in the T-linear
      resistivity (non-Fermi-liquid) regime. Unusually small single-particle hopping
      and unconventional quasiparticle dynamics may have implications for understanding
      the phase of matter realized in this new class of a strongly interacting quantum
      system.

PMID- 15245115
TI  - ARPES on Na0.6CoO2: Fermi surface and unusual band dispersion.
AB  - The electronic structure of single crystals Na0.6CoO2, which are closely related
      to the superconducting Na0.3CoO2.yH(2)O (T(c) approximately 5 K), is studied by
      angle-resolved photoelectron spectroscopy. While the measured Fermi surface (FS)
      is consistent with the large FS enclosing the Gamma point from the band theory,
      the predicted small FS pockets near the K points are absent. In addition, the
      band dispersion is found to be highly renormalized, and anisotropic along the two
      principal axes (Gamma-K, Gamma-M). Our measurements also indicate that an
      extended flatband is formed slightly above E(F) along Gamma-K.

PMID- 15245116
TI  - Dimerization in a half-filled one-dimensional extended hubbard model.
AB  - We use a density-matrix renormalization group method to study quantitatively the
      phase diagram of a one-dimensional extended Hubbard model at half filling by
      investigating the correlation functions and structure factors. We confirmed the
      existence of a novel narrow region with long-range bond-order-wave order that was
      highly controversial recently between the charge-density-wave phase and Mott
      insulator phase. We determined accurately the position of the bicritical point
      U(b) approximately 7.2t, V(b) approximately 3.746t, which is quite different from
      previous studies.

PMID- 15245117
TI  - Exact bond ordered ground state for the transition between the band and the Mott
      insulator.
AB  - We derive an effective Hamiltonian H(eff) for an ionic Hubbard chain, valid for
      t<<U,Delta, where t is the hopping, U is the Coulomb repulsion, and Delta is the
      charge-transfer energy. H(eff) is the minimal model for describing the transition
      between the band insulator (BI) (Delta-U>>t) and the Mott insulator (MI) (U
      Delta>>t). Using spin-particle transformations [Phys. Rev. Lett. 86, 1082
      (2001)]], we map H(eff)(U=Delta) into an SU(3) antiferromagnetic Heisenberg model
      whose exact ground state is known. In this way, we show rigorously that a
      spontaneously dimerized insulating ferroelectric phase appears in the transition
      region between the BI and the MI.

PMID- 15245118
TI  - Coulomb drag as a probe of the nature of compressible States in a magnetic field.
AB  - Magnetodrag reveals the nature of compressible states and the underlying
      interplay of disorder and interactions. At nu=3/2 clear T(4/3) dependence is
      observed, which signifies the metallic nature of the N=0 Landau level. In
      contrast, drag in higher Landau levels reveals an additional contribution, which
      anomalously grows with decreasing T before turning to zero following a thermal
      activation law. The anomalous drag is discussed in terms of electron-hole
      asymmetry arising from disorder and localization, and the crossover to normal
      drag at high fields as due to screening of disorder.

PMID- 15245119
TI  - Band-structure modulation in carbon nanotube T junctions.
AB  - We show that the band structure of metallic carbon nanotubes can be dramatically
      altered by the local electrostatic field. This is realized by coupling chemically
      functionalized nanotubes to form T junctions. The bar of the T is the conducting
      channel and the leg of the T is used for local gating. Transport measurements
      reveal that an energy gap develops upon application of a local electric field in
      both devices with or without linker molecules at the junction. We propose that
      the mechanism of the band gap modulation in the T junctions without linker
      molecules is the field effect, with the linker molecules introducing additional
      electromechanical and chemical effects.

PMID- 15245120
TI  - Coulomb scattering in a 2D interacting electron gas and production of EPR pairs.
AB  - We propose a setup to generate nonlocal spin Einstein-Podolsky-Rosen pairs via
      pair collisions in a 2D interacting electron gas, based on constructive two
      particle interference in the spin-singlet channel at the pi/2 scattering angle.
      We calculate the scattering amplitude via the Bethe-Salpeter equation in the
      ladder approximation and small r(s) limit and find that the Fermi sea leads to a
      substantial renormalization of the bare scattering process. From the scattering
      length, we estimate the current of spin-entangled electrons and show that it is
      within experimental reach.

PMID- 15245121
TI  - Dependence of spin susceptibility of a two-dimensional electron system on the
      valley degree of freedom.
AB  - We report measurements of the spin susceptibility, chi proportional, variant
      g(v)g*m*, in an AlAs two-dimensional electron system where, via the application
      of in-plane stress, we transfer electrons from one ellipsoidal conduction-band
      valley to another (g(v) is the valley degeneracy, and m* and g* are the electron
      effective mass and g factor). At a given density, when the two valleys are
      equally populated (g(v)=2), the measured g*m* is smaller than when only one
      valley is occupied (g(v)=1). This observation counters the common assumption that
      a two-valley two-dimensional system is effectively more dilute than a single
      valley system because of its smaller Fermi energy.

PMID- 15245122
TI  - Charge ordering, commensurability, and metallicity in the phase diagram of the
      layered NaxCoO2.
AB  - The phase diagram of nonhydrated NaxCoO2 has been determined by changing the Na
      content x using a series of chemical reactions. As x increases from 0.3, the
      ground state goes from a paramagnetic metal to a charge-ordered insulator (at
      x=1/2), then to a "Curie-Weiss metal" (around 0.70), and finally to a weak-moment
      magnetically ordered state (x>0.75). The unusual properties of the state at 1/2
      (including particle-hole symmetry at low T and enhanced thermal conductivity) are
      described. The strong coupling between the Na ions and the holes is emphasized.

PMID- 15245123
TI  - Dephasing in disordered metals with superconductive grains.
AB  - The temperature dependence of electron dephasing time tau(phi)(T) is calculated
      for a disordered metal with a small concentration of superconductive grains.
      Above the macroscopic superconducting transition line, when electrons in the
      metal are normal, Andreev reflection from the grains leads to a nearly
      temperature-independent contribution to the dephasing rate. In a broad
      temperature range tau(-1)(phi)(T) strongly exceeds the prediction of the
      classical theory of dephasing in normal disordered conductors, whereas
      magnetoresistance is dominated (in two dimensions) by the Maki-Tompson correction
      and is positive.

PMID- 15245124
TI  - Spin dynamics of the electron-doped high-T(c) superconducting cuprates.
AB  - We show that a basic difference between the electron- and hole-doped cuprates is
      their proximity to two different quantum critical points in a 2D free fermion
      system on a square lattice and that the spin dynamics observed recently for the
      first time in the electron-doped Nd2-xCexCuO4, very different from that in the
      hole-doped cuprates, can be understood as a consequence of this effect.

PMID- 15245125
TI  - Quantum phase transitions in the cuprate superconductor Bi2Sr2-xLaxCuO6+delta.
AB  - To elucidate a quantum phase transition (QPT) in Bi(2)Sr(2-x)La(x)CuO(6+delta),
      we measure charge and heat transport properties at very low temperatures and
      examine the following characteristics for a wide range of doping: normal-state
      resistivity anisotropy under 58 T, temperature dependence of the in-plane thermal
      conductivity kappa(ab), and the magnetic-field dependence of kappa(ab). It turns
      out that all of them show signatures of a QPT at the 1/8 hole doping. Together
      with the recent normal-state Hall measurements under 58 T that signified the
      existence of a QPT at optimum doping, the present results indicate that there are
      two QPTs in the superconducting doping regime of this material.

PMID- 15245126
TI  - Lattice gas dynamics: application to driven vortices in two dimensional
      superconductors.
AB  - A continuous time Monte Carlo lattice gas dynamics is developed to model driven
      steady states of vortices in two dimensional superconducting networks. Dramatic
      differences are found when compared to a simpler Metropolis dynamics. Subtle
      finite size effects are found at low temperature, with a moving smectic that
      becomes unstable to an anisotropic liquid on sufficiently large length scales.

PMID- 15245127
TI  - Off-site repulsion-induced triplet superconductivity: a possibility for chiral
      p(x+y)-wave pairing in Sr2RuO4.
AB  - In order to probe the effect of charge fluctuations on triplet pairing, we study
      the pairing symmetry in the one-band Hubbard model having the off-site Coulomb
      repulsion (V) on top of the on-site repulsion as a model for the gamma band of
      Sr2RuO4, a strong candidate for a triplet pairing superconductor. The result,
      obtained with the dynamical cluster approximation combined with the quantum Monte
      Carlo method, and confirmed from the fluctuation exchange approximation, shows
      that while d(x(2)-y(2)) pairing dominates over p in the absence of V,
      introduction of V makes p(x+y) and d(xy) dominant. The gap function for the
      chiral p(x+y)+ip(x-y) has nodes that are consistent with the recent measurement
      of specific heat in rotated magnetic fields in the ruthenate. This suggests that
      the off-site repulsion may play an essential role in triplet superconductivity in
      this material.

PMID- 15245128
TI  - Creation of an antiferromagnetic exchange spring.
AB  - We present evidence for the creation of an exchange spring in an antiferromagnet
      due to exchange coupling to a ferromagnet. X-ray magnetic linear dichroism
      spectroscopy on single crystal Co/NiO(001) shows that a partial domain wall is
      wound up at the surface of the antiferromagnet when the adjacent ferromagnet is
      rotated by a magnetic field. We determine the interface exchange stiffness and
      the antiferromagnetic domain wall energy from the field dependence of the
      direction of the antiferromagnetic axis, the antiferromagnetic pendant to a
      ferromagnetic hysteresis loop. The existence of a planar antiferromagnetic domain
      wall, proven by our measurement, is a key assumption of most exchange bias
      models.

PMID- 15245129
TI  - Inelastic ultraviolet scattering from high frequency acoustic modes in glasses.
AB  - The dynamic structure factor of vitreous silica and glycerol has been measured as
      a function of temperature and of the momentum transfer up to Q=0.105 nm(-1) using
      a novel experimental technique, the inelastic ultraviolet scattering. As in the
      case of Brillouin light scattering and ultrasonic measurements, the temperature
      dependence of the acoustic attenuation shows a plateau below the glass transition
      whose amplitude scales as Q2. Moreover, a slight temperature dependence of
      attenuation has been found in vitreous silica at about 130 K, which seems to be
      reminiscent of the peak measured at lower Qs. These two findings strongly support
      the idea that anharmonicity is responsible for sound attenuation at ultrasonic
      and hypersonic frequencies. Finally, we demonstrate that the attenuation
      mechanism should show a change of regime between 0.105 and 1 nm(-1).

PMID- 15245130
TI  - Exciton regeneration at polymeric semiconductor heterojunctions.
AB  - Control of the band-edge offsets at heterojunctions between organic
      semiconductors allows efficient operation of either photovoltaic or light
      emitting diodes. We investigate systems where the exciton is marginally stable
      against charge separation and show via E-field-dependent time-resolved
      photoluminescence spectroscopy that excitons that have undergone charge
      separation at a heterojunction can be efficiently regenerated. This is because
      the charge transfer produces a geminate electron-hole pair (separation 2.2-3.1
      nm) which may collapse into an exciplex and then endothermically (E(A)=100-200
      meV) back transfer towards the exciton.

PMID- 15245131
TI  - Can laser light cool semiconductors?
AB  - Laser cooling in semiconductors is theoretically investigated including arbitrary
      external efficiency and photon recycling. Experimental conditions needed to
      attain net cooling in GaAs are derived.

PMID- 15245132
TI  - Energy loss of photoelectrons by interaction with image charge.
AB  - By measuring the photoelectron spectra of the Cu(001) and Cu(110) surfaces
      excited by tunable-laser photons of very low energy (4.50-4.95 eV), we have found
      that the photoelectron can lose energy through interaction with its image charge.
      This energy loss occurs just outside the solid surface and appears as a spike
      structure at the vacuum edge in the photoemission spectra. The requirement for
      observing this energy loss structure is the absence of unoccupied states at the
      vacuum level at the Gamma point to which zero kinetic energy electrons can
      return.

PMID- 15245133
TI  - Entanglement energetics at zero temperature.
AB  - We show how many-body ground state entanglement information may be extracted from
      subsystem energy measurements at zero temperature. Generically, the larger the
      measured energy fluctuations are, the larger the entanglement is. Examples are
      given with the two-state system and the harmonic oscillator. Comparisons made
      with recent qubit experiments show that this type of measurement provides another
      method to quantify entanglement with the environment.

PMID- 15245134
TI  - Interfacing quantum-optical and solid-state qubits.
AB  - We present a generic model of coupling quantum-optical and solid-state qubits,
      and the corresponding transfer protocols. The example discussed is a trapped ion
      coupled to a charge qubit (e.g., Cooper pair box). To enhance the coupling and to
      achieve compatibility between the different experimental setups we introduce a
      superconducting cavity as the connecting element.

PMID- 15245135
TI  - Scaling of microtubule force-velocity curves obtained at different tubulin
      concentrations.
AB  - We present a single curve that describes the decay in average growth velocity for
      microtubules in response to a mechanical force. Curves obtained at two new and
      one previously studied tubulin concentrations coalesce when normalized with the
      growth velocity at zero load. This scaling provides direct evidence for a force
      independent molecular off rate, in agreement with Brownian ratchet models. In
      addition, microtubule length changes were measured with a precision up to 10 nm,
      revealing that microtubules under load abruptly switch between different growth
      velocities.

PMID- 15245136
TI  - Tracking waves and vortex nucleation in excitable systems with anomalous
      dispersion.
AB  - We report experimental results obtained from a chemical reaction-diffusion system
      in which wave propagation is limited to a finite band of wavelengths and in which
      no solitary pulses exist. Wave patterns increase their size through repeated
      annihilation events of the frontier pulse that allow the succeeding pulses to
      advance farther. A related type of wave dynamics involves a stable but slow
      frontier pulse that annihilates subsequent waves in front-to-back collisions.
      These so-called merging dynamics give rise to an unexpected form of spiral wave
      nucleation. All of these phenomena are reproduced by a simple, three-species
      reaction-diffusion model that reveals the importance of the underlying anomalous
      dispersion relation.

PMID- 15245137
TI  - Shot noise of a quantum shuttle.
AB  - We formulate a theory for shot noise in quantum nanoelectromechanical systems. As
      a specific example, the theory is applied to a quantum shuttle, and the zero
      frequency noise, measured by the Fano factor F, is computed. F reaches very low
      values (F approximately 10(-2)) in the shuttling regime even in the quantum
      limit, confirming that shuttling is universally a low noise phenomenon. In
      approaching the semiclassical limit, the Fano factor shows a giant enhancement (F
      approximately 10(2)) at the shuttling threshold, consistent with predictions
      based on phase-space representations of the density matrix.

PMID- 15245138
TI  - Double layers and interparticle forces in colloid science and biology: analytic
      results for the effect of ionic dispersion forces.
AB  - We study analytically two of the central problems of colloid science: the
      structure of the double layer surrounding a charged particle and the forces
      between two such particles. Traditionally, these have been understood using a
      combination of electrostatic forces acting on the ions and the entropy of the
      same ions. Here we derive explicit formulas showing how the often dominant
      dispersion forces between ions and the surfaces can dramatically change the
      structure of the double layer and the forces.

PMID- 15245139
TI  - Comment on "Solitonlike solutions of the Grad-Shafranov equation".

PMID- 15245141
TI  - Comment on "Search for anomalous effects in H2O/D2O mixtures by neutron total
      cross section measurements".

PMID- 15245143
TI  - Bright Bose-Einstein gap solitons of atoms with repulsive interaction.
AB  - We report on the first experimental observation of bright matter wave solitons
      for 87Rb atoms with repulsive atom-atom interaction. This counterintuitive
      situation arises inside a weak periodic potential, where anomalous dispersion can
      be realized at the Brillouin zone boundary. If the coherent atomic wave packet is
      prepared at the corresponding band edge, a bright soliton is formed inside the
      gap. The strength of our system is the precise control of preparation and real
      time manipulation, allowing the systematic investigation of gap solitons.

PMID- 15245144
TI  - Atom interferometry with trapped fermi gases.
AB  - We realize an interferometer with an atomic Fermi gas trapped in an optical
      lattice under the influence of gravity. The single-particle interference between
      the eigenstates of the lattice results in macroscopic Bloch oscillations of the
      sample. The absence of interactions between fermions allows a time-resolved study
      of many periods of the oscillations, leading to a sensitive determination of the
      acceleration of gravity. The experiment proves the superiority of noninteracting
      fermions with respect to bosons for precision interferometry and offers a way for
      the measurement of forces with microscopic spatial resolution.

PMID- 15245145
TI  - Signatures of superfluidity for Feshbach-resonant Fermi gases.
AB  - We consider atomic Fermi gases where Feshbach resonances can be used to study the
      whole BCS-Bose-Einstein condensate crossover. We show how a probing field
      transferring atoms out of the superfluid can be used to detect the onset of the
      superfluid transition in the high-T(c) and BCS regimes. The number of transferred
      atoms, as a function of the energy given by the probing field, peaks at the gap
      energy. The shape of the peak is asymmetric due to the single particle excitation
      gap. Since the excitation gap also includes a pseudogap contribution, the
      asymmetry alone is not a signature of superfluidity. The incoherent nature of the
      noncondensed pairs leads to broadening of the peak. The broadening decays below
      the critical temperature, causing a drastic increase in the asymmetry. This
      provides a signature of the transition.

PMID- 15245146
TI  - Experimental evidence of coexisting periodic stochastic resonance and coherence
      resonance phenomena.
AB  - We report evidence of coexisting period stochastic resonance (PSR) and coherence
      resonance (CR) phenomena in an electrochemical cell. The anodic voltage (V) in
      the cell is chosen such that the anodic current (I) exhibits excitable fixed
      point behavior. Subsequently, the anodic voltage is modulated by an external
      perturbation that is a composite of a subthreshold periodic pulse signal and
      Gaussian white noise (GWN). As the amplitude of the GWN is increased, the
      regularity of the invoked dynamics is analyzed using normalized variance curve.
      The calculated resonance curve shows a double minima, implying the existence of
      two optimum noise levels where enhanced regularity of the induced spike sequence
      is detected. Numerical simulations corroborate experimental findings.

PMID- 15245147
TI  - Classical and quantum fluctuation theorems for heat exchange.
AB  - The statistics of heat exchange between two classical or quantum finite systems
      initially prepared at different temperatures are shown to obey a fluctuation
      theorem.

PMID- 15245148
TI  - Stability of atomic clocks based on entangled atoms.
AB  - We analyze the effect of realistic noise sources for an atomic clock consisting
      of a local oscillator that is actively locked to a spin-squeezed (entangled)
      ensemble of N atoms. We show that the use of entangled states can lead to an
      improvement of the long-term stability of the clock when the measurement is
      limited by decoherence associated with instability of the local oscillator
      combined with fluctuations in the atomic ensemble's Bloch vector. Atomic states
      with a moderate degree of entanglement yield the maximal clock stability,
      resulting in an improvement that scales as N(1/6) compared to the atomic shot
      noise level.

PMID- 15245149
TI  - New limits on the drift of fundamental constants from laboratory measurements.
AB  - We have remeasured the absolute 1S-2S transition frequency nu(H) in atomic
      hydrogen. A comparison with the result of the previous measurement performed in
      1999 sets a limit of (-29+/-57) Hz for the drift of nu(H) with respect to the
      ground state hyperfine splitting nu(Cs) in 133Cs. Combining this result with the
      recently published optical transition frequency in 199Hg+ against nu(Cs) and a
      microwave 87Rb and 133Cs clock comparison, we deduce separate limits on
      alpha/alpha=(-0.9+/-2.9) x 10(-15) yr(-1) and the fractional time variation of
      the ratio of Rb and Cs nuclear magnetic moments mu(Rb)/mu(Cs) equal to (-0.5+/
      1.7) x 10(-15) yr(-1). The latter provides information on the temporal behavior
      of the constant of strong interaction.

PMID- 15245151
TI  - Nuclear stopping from 0.09A to 1.93A GeV and its correlation to flow.
AB  - We present a complete systematics (excitation functions and system-size
      dependences) of global stopping and side flow for heavy ion reactions in the
      energy range between 0.09A and 1.93A GeV. For the heaviest system, Au+Au, we
      observe a plateau of maximal stopping extending from about 0.2A to 0.8A GeV with
      a fast drop on both sides. The degree of stopping, which is shown to remain
      significantly below the expectations of a full stopping scenario, is found to be
      highly correlated to the amount of side flow.

PMID- 15245152
TI  - Deformation of the N=Z nucleus 76Sr using beta-decay studies.
AB  - A novel method of deducing the deformation of the N=Z nucleus 76Sr is presented.
      It is based on the comparison of the experimental Gamow-Teller strength
      distribution B(GT) from its beta decay with the results of quasi-random-phase
      approximation calculations. This method confirms previous indications of the
      strong prolate deformation of this nucleus in a totally independent way. The
      measurement has been carried out with a large total absorption gamma
      spectrometer, "Lucrecia," newly installed at CERN-ISOLDE.

PMID- 15245150
TI  - Wess-Zumino current and the structure of the decay tau- -->K- pi- K+ nu tau.
AB  - We present the first study of the vector (Wess-Zumino) current in tau(-)-->K-pi
      K+nu(tau) decay using data collected with the CLEO III detector at the Cornell
      Electron Storage Ring. We determine the quantitative contributions to the decay
      width from the vector and axial vector currents. Within the framework of a model
      by Kuhn and Mirkes, we identify the quantitative contributions to the total decay
      rate from the intermediate states omegapi, rho(')pi, and K*K.

PMID- 15245153
TI  - Analog states of 7He observed via the 6He(p,n) reaction.
AB  - Isobaric analog states of 7He have been investigated by a novel technique
      involving the observation of the resonant yield of neutrons from the 6He(p,n)
      reaction in coincidence with gamma rays from the decay of the (0(+),T=1) state in
      6Li. The gamma rays provide a clean signature for the isospin-conserving neutron
      decay of the low-lying isobaric analog resonances. It is conclusively shown that
      the analog of the recently observed low-lying spin-orbit partner of the 7He
      ground state does not exist. Evidence is presented that this state lies at much
      higher energies, in agreement with microscopic calculations.

PMID- 15245154
TI  - Radiative corrections to the polarizability of helium.
AB  - The complete alpha(3) QED correction to the helium atom polarizability is
      computed assuming an infinite nuclear mass and found to be equal to
      0.000030666(3) a.u., with the contribution from the electric-field dependence of
      the Bethe logarithm amounting to 0.000000193(2) a.u. After including the alpha(2)
      and alpha(3) corrections for the nuclear recoil and the leading part of the
      alpha(4) QED correction, we find that the molar polarizability of 4He is
      0.51725419(9)(4) cm(3)/mol. The first of the two error bounds is dominated by the
      uncertainty of alpha(4) and higher-order QED corrections and the second reflects
      the uncertainty of the Avogadro constant.

PMID- 15245155
TI  - Dynamically and quasiforbidden transitions in photoionization of open-shell
      atoms: a combined experimental and theoretical study.
AB  - Completely fine-structure-resolved photoelectron spectra produced from sodium
      atoms selectively excited into the Na* 2p(6)3p (2)P(1/2) and (2)P(3/2) states
      were obtained using a third generation synchrotron source in conjunction with
      laser pumping and high-resolution spectrometry. The spectra show dramatically
      different behaviors. The strong variations observed in the regions of the Na+
      2p(5)3p (1,3)L(J) photolines and the Na+ 2p(5)4p (1,3)L(J) shakeup satellites are
      explained within a generalized geometrical model, accounting for the intermediate
      angular momentum coupling in the ionic states.

PMID- 15245156
TI  - Identifying entanglement using quantum ghost interference and imaging.
AB  - We report a quantum interference and imaging experiment which allows identifying
      the entanglement in momentum and position variables of a two-photon system. The
      measurements show indeed that the uncertainties in the sum of momenta and in the
      difference of positions of the entangled two-photon satisfy both EPR inequalities
      Delta(k(1)+k(2))<min((Delta k(1),Delta k(2)) and Delta(x(1)-x(2))<min((Delta
      x(1),Delta x(2)). These two inequalities, together, represent a nonclassicality
      condition. Our measurements provide a direct way to distinguish between quantum
      entanglement and classical correlation in continuous variables for systems of
      pairs of photons.

PMID- 15245157
TI  - Inadequacy of perfect-reflector models in cavity QED for systems with low
      frequency excitations.
AB  - It is shown that the model of perfectly reflecting boundaries widely employed in
      cavity QED is unsuitable for systems that have long-wavelength excitations. A
      prime example is a free charged particle near a reflecting wall. Modeling the
      wall as perfectly reflecting from the outset ignores evanescent waves that couple
      to the particle through virtual excitations at low energies, which can lead to
      errors in order of magnitude and even sign. The example of a free electron near
      an imperfectly reflecting wall characterized by a constant frequency-independent
      refractive index n is investigated in detail by determining its energy shift
      relative to an electron in vacuum through both nonrelativistic and relativistic
      calculations.

PMID- 15245158
TI  - Theory of the Kapitza-Dirac diffraction effect.
AB  - We treat the Kapitza-Dirac diffraction effect observed recently by Batelaan et
      al. using a newly developed nonperturbative quantum-field scattering theory. Our
      theory shows that an electron beam passing perpendicularly through a focused
      standing light wave can produce diffraction patterns. Our theory predicts (1) the
      minimum value of the ponderomotive energy is (Planck's over 2 pi
      omega)(2)/m(e)c(2), (2) the critical laser intensity above which the first pair
      of electron diffraction peaks will occur, and (3) the existence of sidebands in
      the electron spectra separated far from the central band by a momentum of several
      hundred photons. Our theory provides a unified explanation of the experimental
      results of Bucksbaum et al. and Batelaan et al.

PMID- 15245159
TI  - Escaping from nonhyperbolic chaotic attractors.
AB  - The noise-induced escape process from a nonhyperbolic chaotic attractor is of
      physical and fundamental importance. We address this problem by uncovering the
      general mechanism of escape in the relevant low noise limit using the Hamiltonian
      theory of large fluctuations and by establishing the crucial role of the primary
      homoclinic tangency closest to the basin boundary in the dynamical process. In
      order to demonstrate that, we provide an unambiguous solution of the variational
      equations from the Hamiltonian theory. Our results are substantiated with the
      help of physical and dynamical paradigms, such as the Henon and the Ikeda maps.
      It is further pointed out that our findings should be valid for driven flow
      systems and for experimental data.

PMID- 15245160
TI  - Theory of pattern formation of metallic microparticles in poorly conducting
      liquids.
AB  - We develop a continuum theory of self-assembly and pattern formation in metallic
      microparticles immersed in a poorly conducting liquid in a dc electric field. The
      theory is formulated in terms of conservation laws for the densities of immobile
      particles (precipitate) and bouncing particles (gas) coupled to the Navier-Stokes
      equation for the liquid. This theory successfully reproduced the correct topology
      of the phase diagram and primary patterns observed in the experiment [Phys. Rev.
      Lett. 90, 114301 (2003)]]: static crystals, honeycombs, dynamic pulsating rings,
      and rotating multipetal vortices.

PMID- 15245161
TI  - Blue sky catastrophe in double-diffusive convection.
AB  - A global bifurcation of the blue sky catastrophe type has been found in a small
      Prandtl number binary mixture contained in a laterally heated cavity. The system
      has been studied numerically applying the tools of bifurcation theory. The
      catastrophe corresponds to the destruction of an orbit which, for a large range
      of Rayleigh numbers, is the only stable solution. This orbit is born in a global
      saddle-loop bifurcation and becomes chaotic in a period-doubling cascade just
      before its disappearance at the blue sky catastrophe.

PMID- 15245162
TI  - Plasma rotation induced by directed waves in the ion-cyclotron range of
      frequencies.
AB  - Changes of the toroidal plasma rotation induced by directed waves in the ion
      cyclotron range of frequencies (ICRF) have been identified experimentally for the
      first time on the JET tokamak. The momentum carried by the waves is initially
      absorbed by fast resonating ions, which subsequently transfer it to the bulk
      plasma. Thus, the results provide evidence for the influence of ICRF heated fast
      ions on plasma rotation.

PMID- 15245163
TI  - Guiding of intense laser beams in highly ionized plasma columns generated by a
      fast capillary discharge.
AB  - We have demonstrated the guiding of laser pulses with peak intensities up to 2.2
      x 10(17) W/cm(2) in a 5.5 cm long plasma column containing highly charged Ar ions
      generated by a fast capillary discharge. A rapid discharge-driven hydrodynamic
      compression guides progressively lower order modes through a plasma with
      increasing density and degree of ionization, until the guide collapses on axis.
      The lowest order mode (FWHM approximately 50 microm) is guided with 75%
      transmission efficiency shortly before the plasma reaches the conditions for
      lasing in Ne-like Ar. The subsequent rapid plasma expansion forms a significantly
      leakier and more absorbent guide.

PMID- 15245164
TI  - Suppression of large edge-localized modes in high-confinement DIII-D plasmas with
      a stochastic magnetic boundary.
AB  - A stochastic magnetic boundary, produced by an applied edge resonant magnetic
      perturbation, is used to suppress most large edge-localized modes (ELMs) in high
      confinement (H-mode) plasmas. The resulting H mode displays rapid, small
      oscillations with a bursty character modulated by a coherent 130 Hz envelope. The
      H mode transport barrier and core confinement are unaffected by the stochastic
      boundary, despite a threefold drop in the toroidal rotation. These results
      demonstrate that stochastic boundaries are compatible with H modes and may be
      attractive for ELM control in next-step fusion tokamaks.

PMID- 15245165
TI  - Destabilization of fast-ion-induced long sawteeth by localized current drive in
      the JET tokamak.
AB  - In a tokamak fusion reactor the energetic alpha particles will transiently
      stabilize the magnetohydrodynamic activity causing sawtooth oscillations. The
      crash events terminating long sawtooth free periods can provide seed islands for
      neoclassical tearing modes [Phys. Rev. Lett. 88, 105001 (2002)]]. To shorten the
      sawtooth periods localized current drive near the q=1 surface is a possibility.
      This Letter provides the first experimental evidence for the effectiveness of
      this method in the different physics regime associated with fast-ion-induced long
      sawteeth on the JET tokamak.

PMID- 15245166
TI  - Validation of neoclassical bootstrap current models in the edge of an H-mode
      plasma.
AB  - Analysis of the parallel electric field E(parallel) evolution following an L-H
      transition in the DIII-D tokamak indicates the generation of a large negative
      pulse near the edge which propagates inward, indicative of the generation of a
      noninductive edge current. Modeling indicates that the observed E(parallel)
      evolution is consistent with a narrow current density peak generated in the
      plasma edge. Very good quantitative agreement is found between the measured
      E(parallel) evolution and that expected from neoclassical theory predictions of
      the bootstrap current.

PMID- 15245167
TI  - Phonon-roton excitations in liquid 4He at negative pressures.
AB  - We present neutron scattering measurements of the phonon-roton excitations of
      superfluid 4He held at negative pressures from zero to -5 bar. The liquid was
      stretched to negative pressures by immersing it in the porous medium MCM-41. In
      the wave vector range 0.35< or =Q< or =1.55 A(-1) and temperature T=0.4 K
      investigated, the phonon and maxon energies decrease systematically below bulk
      values as the negative pressure is increased. The energies are consistent with
      extrapolation of positive pressure values from which the negative internal
      pressure can be estimated. The maximum negative pressure realized is consistent
      with surface tension arguments and the MCM-41 pore diameter of 47 A.

PMID- 15245168
TI  - Stochastic dynamics of nanoscale mechanical oscillators immersed in a viscous
      fluid.
AB  - The stochastic response of nanoscale oscillators of arbitrary geometry immersed
      in a viscous fluid is studied. Using the fluctuation-dissipation theorem, it is
      shown that deterministic calculations of the governing fluid and solid equations
      can be used in a straightforward manner to directly calculate the stochastic
      response that would be measured in experiment. We use this approach to
      investigate the fluid coupled motion of single and multiple cantilevers with
      experimentally motivated geometries.

PMID- 15245169
TI  - Density-of-states Monte Carlo simulation of a binary glass.
AB  - A newly proposed Monte Carlo formalism has been used to simulate a glass-forming
      liquid above and below the glass transition temperature. The heat capacity
      exhibits a sharp peak at a temperature lower than that reported from extensive
      molecular dynamics simulations. Its height is larger than that reported earlier.
      At temperatures below mode coupling, the average inherent-structure energy of the
      configurations generated in this work is significantly lower than that reported
      in the literature. The entropy of the supercooled liquid is calculated directly
      from our simulations and that of a disordered solid is calculated by a normal
      mode analysis. We find that at low temperatures these two entropy curves become
      essentially parallel. They do not intersect each other, raising questions about
      the existence of a Kauzmann temperature in this glass-forming mixture.

PMID- 15245170
TI  - Solid-solid phase transformation via virtual melting significantly below the
      melting temperature.
AB  - A new phenomenon is theoretically predicted, namely, that solid-solid
      transformation with a relatively large transformation strain can occur through
      virtual melting along the interface at temperatures significantly (more than 100
      K) below the melting temperature. The energy of elastic stresses, induced by
      transformation strain, increases the driving force for melting and reduces the
      melting temperature. Immediately after melting, the stresses relax and the
      unstable melt solidifies. Fast solidification in a thin layer leads to nanoscale
      cracking, which does not affect the thermodynamics and kinetics of solid-solid
      transformation. Seven theoretical predictions are in quantitative agreement with
      experiments conducted on the beta-->delta transformation in the HMX energetic
      crystal.

PMID- 15245171
TI  - Surface crystallization of amorphous solid water.
AB  - We demonstrate that the crystallization of thin, supported amorphous solid water
      layers is initiated at the water surface. This is concluded from the observation
      of sequential crystallization of amorphous water at the surface, in the bulk, and
      at the water-support interface. A surface nucleation model quantitatively
      reproduces the observed transformation kinetics at the three sites.

PMID- 15245172
TI  - Anomalous dielectric behavior of water in ionic newton black films.
AB  - The electrostatics of two charged surfactant layers in aqueous media
      (surfactant/water/surfactant films) is investigated using molecular dynamics
      simulations. In the films studied (with a surfactant-surfactant distance from
      approximately 35 A to contact) we observe an anomalous dielectric response of
      water. The electrostatic potential phi(z) inside the aqueous core of the films
      (containing bulk water with rho=1 g/cm(3)) is completely different from that
      expected for a film containing a dielectric medium with the dielectric constant
      of water. In addition, our results are not consistent with a local relation
      between the water polarization P(z)(z) and the electric field E(z)(z). The
      polarization P(z)(z) is maximum at the interfaces (due to solvent molecules
      forming part of the structure of the surfactant layers) and decays from the
      interfaces inside the aqueous core with a decay length of order of approximately
      10 A.

PMID- 15245173
TI  - Circular dichroism in core level photoemission from an adsorbed chiral molecule.
AB  - The results of experimental measurements and theoretical simulations of circular
      dichroism in the angular dependence (CDAD) of photoemission from atomic core
      levels of each of the enantiomers of a chiral molecule, alanine, adsorbed on
      Cu(110) are presented. Measurements in, and out of, substrate mirror planes
      distinguish CDAD due to the chirality of the sample and the experimental
      geometry. The effect due to sample chirality is relatively weak, so such
      measurements may not provide a routine spectral fingerprint of adsorbate
      chirality.

PMID- 15245174
TI  - Persistent droplet motion in liquid-liquid dewetting.
AB  - When a nonvolatile liquid film dewets from a partly compatible liquid substrate,
      the advancing dewetting front leaves behind droplets formed through a Rayleigh
      instability mechanism at its rim. We have found that these droplets continue to
      move in the direction of the dewetting front for extended periods (of order one
      day) with an initial droplet velocity varying linearly with the droplet size, and
      a displacement varying logarithmically with time. We attribute this persistent
      motion to a transient surface tension gradient on the substrate liquid surface
      trailing the dewetting front.

PMID- 15245175
TI  - Kinetics in surface reconstructions on GaAs(001).
AB  - We have successfully controlled the surface structures of GaAs(001) by changing
      incident As-molecular species. Under As4 fluxes, the c(4 x 4) reconstruction with
      Ga-As dimers [c(4 x 4)alpha structure] is obtained, but the formation of three As
      As dimer structures [c(4 x 4)beta structure] is kinetically limited. On the other
      hand, the structure change from the (2 x 4), through c(4 x 4)alpha, to c(4 x
      4)beta phases is observed under As2 fluxes. We found that the c(4 x 4)alpha
      structure is energetically metastable and provides a kinetic pathway for the
      structure change between the (2 x 4) and c(4 x 4)beta phases under As2 fluxes.

PMID- 15245176
TI  - Ground state phases of the half-filled one-dimensional extended hubbard model.
AB  - Using quantum Monte Carlo simulations, results of a strong-coupling expansion,
      and Luttinger liquid theory, we determine quantitatively the ground state phase
      diagram of the one-dimensional extended Hubbard model with on-site and nearest
      neighbor repulsions U and V. We show that spin frustration stabilizes a bond
      ordered (dimerized) state for U approximately V/2 up to U/t approximately 9,
      where t is the nearest-neighbor hopping. The transition from the dimerized state
      to the staggered charge-density-wave state for large V/U is continuous for U < or
      approximately 5.5 and first order for higher U.

PMID- 15245177
TI  - Influence of the incommensurability in Sr14-xCaxCu24O41 Family Compounds.
AB  - We study the influence of the structural modulation on the low energy physics of
      the Sr14-xCaxCu24O41 oxides, using ab initio determination of the on-site and
      nearest-neighbor effective parameters. The structural modulations appear to be
      the key degree of freedom responsible for the low energy properties, such as the
      electron localization, the formation of dimers in the x=0 compound, or the
      antiferromagnetic order in the x=13.6 compound.

PMID- 15245179
TI  - Spin-charge separation in two-dimensional frustrated quantum magnets.
AB  - The dynamics of a mobile hole in two-dimensional frustrated quantum magnets is
      investigated by exact diagonalization techniques. Our results provide evidence
      for spin-charge separation upon doping the kagome lattice, a prototype of a spin
      liquid. In contrast, in the checkerboard lattice, a symmetry broken valence bond
      crystal, a small quasiparticle peak is seen for some crystal momenta, a finding
      interpreted as a restoration of weak holon-spinon confinement.

PMID- 15245178
TI  - Two-dimensional charge order in layered 2-1-4 perovskite oxides.
AB  - Monte Carlo simulations are performed on the three-dimensional (3D) Ising model
      with the 2-1-4 layered perovskite structure as a minimal model for checkerboard
      charge ordering phenomena in layered perovskite oxides. Because of the interlayer
      frustration, only 2D long-range order emerges with a finite correlation length
      along the c axis. Critical exponents of the transition change continuously as a
      function of the interlayer coupling constant. The interlayer long-range Coulomb
      interaction decays exponentially and is negligible even between the second
      neighbor layers. Instead, monoclinic distortion of a tetragonal unit cell lifts
      the macroscopic degeneracy to induce a 3D charge ordering. The dimensionality of
      the charge order in La0.5Sr1.5MnO4 is discussed from this viewpoint.

PMID- 15245180
TI  - Effects of nitridation on the characteristics of silicon dioxide: dielectric and
      structural properties from ab initio calculations.
AB  - By combining ab initio calculations and classical molecular dynamics, we
      determine how the inclusion of nitrogen in a silica matrix changes its dielectric
      constant, and elucidate the underlying mechanisms. We find that there is an
      entire range of nitrogen concentrations (up to approximately 25%) for which the
      structural pattern of the oxide is preserved in bulk SiON, and the dielectric
      constant increases mainly because of the variation of the ionic polarizability.
      This behavior is not sensitive to hydrogen passivation of nitrogen. The few
      defects, which are associated with electron states near the gap, are mainly
      centered on undercoordinated nitrogen and undercoordinated silicon, and tend to
      be removed by hydrogen.

PMID- 15245181
TI  - Ultrafast dynamic control of spin and charge density oscillations in a GaAs
      quantum well.
AB  - We use subpicosecond laser pulses to generate and monitor in real time collective
      oscillations of electrons in a modulation-doped GaAs quantum well. The observed
      frequencies match those of intersubband spin- and charge-density excitations.
      Light couples to coherent density fluctuations through resonant stimulated Raman
      scattering. Because the spin- and charge-related modes obey different selection
      rules and resonant behavior, the amplitudes of the corresponding oscillations can
      be independently controlled by using shaped pulses of the proper polarization.

PMID- 15245182
TI  - Theory of plasmon-assisted transmission of entangled photons.
AB  - The recent surface plasmon entanglement experiment [Nature (London) 418, 304
      (2002)]] is theoretically analyzed. The entanglement preservation upon
      transmission in the nonfocused case is found to provide information about the
      interaction of the biphoton and the metallic film. The entanglement degradation
      in the focused case is explained in the framework of a fully multimode model.
      This phenomenon is a consequence of the polarization-selective filtering behavior
      of the metallic nanostructured film. It is shown that the "which-way" labels that
      degrade entanglement are not located in the degrees of freedom of the metallic
      film but rather in the spatial degrees of freedom of the photon field.

PMID- 15245183
TI  - Two-dimensional electron-hole liquid in single Si quantum wells with large
      electronic and dielectric confinement.
AB  - We report a luminescence study of the electronic properties of the 2D electron
      hole liquid in crystalline Si quantum wells with SiO2 dielectric barriers. The
      Fermi-Dirac condensation of e-h pairs into a metallic liquid is strongly enhanced
      by spatial localization. We present experimental evidence for the formation of
      liquid nanodroplets, with size increasing with e-h pair density. The quantum
      confined regime is observed for well width below 15 nm. The data are analyzed in
      a confinement model that takes account of the band-gap renormalization by 2D many
      body effects and the increase of the Coulomb interactions due to the dielectric
      mismatch between the Si well and the SiO2 barriers.

PMID- 15245184
TI  - New type of B-periodic magneto-oscillations in a two-dimensional electron system
      induced by microwave irradiation.
AB  - We observe a new type of magneto-oscillations in the photovoltage and the
      longitudinal resistance of a two-dimensional electron system. The oscillations
      are induced by microwave radiation and are periodic in magnetic field. The period
      is determined by the microwave frequency, the electron density, and the distance
      between potential probes. The phenomenon is accounted for by interference of
      coherently excited edge magnetoplasmons in the contact regions and offers
      perspectives for developing new tunable microwave and terahertz detection schemes
      and spectroscopic techniques.

PMID- 15245185
TI  - Theoretical and experimental studies of carbon nanotube electromechanical
      coupling.
AB  - We present an investigation into electromechanical coupling in carbon nanotubes
      by focusing on phonon frequency shifts as a result of charge injection. A nearest
      neighbor, tight-binding theoretical model is accompanied by a computational
      explication carried out using the Vienna ab initio simulation package density
      functional theory code. Raman spectroscopic measurements of the electromechanic
      couplings under varied but controlled charge injection conditions are also
      carried out, and the close agreement between the model results and the measured
      Raman peak shifts suggests that geometrical changes of charged carbon nanotubes
      previously observed or speculated in different experiments can indeed originate
      from the simple quantum effects described herein.

PMID- 15245186
TI  - Quantum confinement and electronic properties of silicon nanowires.
AB  - We investigate the structural, electronic, and optical properties of hydrogen
      passivated silicon nanowires along [110] and [111] directions with diameter d up
      to 4.2 nm from first principles. The size and orientation dependence of the band
      gap is investigated and the local-density gap is corrected with the GW
      approximation. Quantum confinement becomes significant for d<2.2 nm, where the
      dielectric function exhibits strong anisotropy and new low-energy absorption
      peaks start to appear in the imaginary part of the dielectric function for
      polarization along the wire axis.

PMID- 15245187
TI  - Long-range nonlocal flow of vortices in narrow superconducting channels.
AB  - We report a new nonlocal effect in vortex matter, where an electric current
      confined to a small region of a long and sufficiently narrow superconducting wire
      causes vortex flow at distances hundreds of intervortex separations away. The
      observed remote traffic of vortices is attributed to a very efficient transfer of
      a local strain through the one-dimensional vortex lattice (VL), even in the
      presence of disorder. We also observe mesoscopic fluctuations in the nonlocal
      vortex flow, which arise due to "traffic jams" when vortex arrangements do not
      match a local geometry of a superconducting channel.

PMID- 15245188
TI  - Evidence for the coexistence of an anisotropic superconducting gap and nonlocal
      effects in the nonmagnetic superconductor LuNi2B2C.
AB  - A study of the dependence of the heat capacity C(p)(alpha) on the field angle in
      LuNi2B2C reveals an anomalous disorder effect. For pure samples, C(p)(alpha)
      exhibits a fourfold variation as the field H<H(c2) is rotated in the [001] plane,
      with minima along <100> (alpha=0). A slightly disordered sample, however,
      develops anomalous secondary minima along <110> for mu(0)H>1 T, leading to an
      eightfold pattern at 2 K and 1.5 T. The anomalous pattern is discussed in terms
      of coexisting superconducting gap anisotropy and nonlocal effects.

PMID- 15245189
TI  - Universal conductance of nanowires near the superconductor-metal quantum
      transition.
AB  - We consider wires near a zero temperature transition between superconducting and
      metallic states. The critical theory obeys hyperscaling, which leads to a
      universal frequency, temperature, and length dependence of the conductance;
      quantum and thermal phase slips are contained within this critical theory.
      Normal, superconducting, and mixed (SN) leads on the wire determine distinct
      universality classes. For the SN case, wires near the critical point have a
      universal dc conductance which is independent of the length of the wire at low
      temperatures.

PMID- 15245191
TI  - Ferromagnetic stability in Fe nanodot assemblies on Cu(111) induced by indirect
      coupling through the substrate.
AB  - We report collective ferromagnetic behavior with high Curie temperatures (T(c))
      in Fe dot assemblies supported by the Cu(111) surface. Our ability to tune the
      average size and spacing of the individual dots allows us to conclude that
      enhanced magnetic anisotropy cannot account for this high-T(c) ferromagnetic
      order. Because our Monte Carlo simulations have ruled out the dipolar interaction
      as the dominant factor in this system, we attribute the origin of the
      ferromagnetic order to indirect exchange coupling via the Cu(111) substrate.

PMID- 15245190
TI  - Direct observation of the flux-line vortex glass phase in a type II
      superconductor.
AB  - The order of the vortex state in La1.9Sr0.1CuO4 is probed using muon-spin
      rotation and small-angle neutron scattering. A transition from a Bragg glass to a
      vortex glass is observed, where the latter is composed of disordered vortex
      lines. In the vicinity of the transition the microscopic behavior reflects a
      delicate interplay of thermally induced and pinning-induced disorder.

PMID- 15245192
TI  - First-principles study of ferromagnetism in epitaxial Si-Mn thin films on
      Si(001).
AB  - Density-functional theory calculations are employed to investigate both the
      epitaxial growth and the magnetic properties of thin Mn and MnSi films on
      Si(001). For single Mn adatoms, we find a preference for the second-layer
      interstitial site. While a monolayer Mn film is energetically unfavorable, a
      capping-Si layer significantly enhances the thermodynamic stability and induces a
      change from antiferromagnetic to ferromagnetic order. For higher Mn coverage, a
      sandwiched Si-Mn thin film (with CsCl-like crystal structure) is found to be the
      most stable epitaxial structure. We attribute the strong ferromagnetic intralayer
      coupling in these films to Mn 3d-Si 3s3p exchange.

PMID- 15245193
TI  - Picosecond dynamics of the photoinduced spin polarization in epitaxial (Ga,Mn)as
      films.
AB  - Static and time-resolved magneto-optical spectra of the ferromagnetic
      semiconductor (Ga,Mn)As show that a pulsed photoexcitation with a fluence of 10
      microJ/cm(2) is equivalent to the application of an external magnetic field of
      about 1 mT, which relaxes with a decay time of 30 ps. This relaxation is
      attributed to the spin relaxation of electrons in the conduction band and is
      found to be not affected by interactions with Mn ions.

PMID- 15245194
TI  - Soft x-ray resonant diffraction study of magnetic and orbital correlations in a
      manganite near half doping.
AB  - We have utilized resonant x-ray diffraction at the Mn L(II,III) edges in order to
      directly compare magnetic and orbital correlations in Pr0.6Ca0.4MnO3. Comparing
      the widths of the magnetic and orbital diffraction peaks, we find that the
      magnetic correlation length exceeds that of the orbital order by nearly a factor
      of 2. Furthermore, we observe a large (approximately 3 eV) spectral weight shift
      between the magnetic and orbital resonant line shapes, which cannot be explained
      within the classic Goodenough picture of a charge-ordered ground state. To
      explain the shift, we calculate the orbital and magnetic resonant diffraction
      line shapes based on a relaxed charge-ordered model.

PMID- 15245195
TI  - Imaging density disturbances in water with a 41.3-attosecond time resolution.
AB  - We show that the momentum flexibility of inelastic x-ray scattering may be
      exploited to invert its loss function, allowing real time imaging of density
      disturbances in a medium. We show the disturbance arising from a point source in
      liquid water, with a resolution of 41.3 attoseconds (4.13 x 10(-17) s) and 1.27 A
      (1.27 x 10(-8) cm). This result is used to determine the structure of the
      electron cloud around a photoexcited chromophore in solution, as well as the wake
      generated in water by a 9 MeV gold ion. We draw an analogy with pump-probe
      techniques and suggest that energy-loss scattering may be applied more generally
      to the study of attosecond phenomena.

PMID- 15245196
TI  - Pinning of tumoral growth by enhancement of the immune response.
AB  - Tumor growth is a surface phenomenon of the molecular beam epitaxy universality
      class in which diffusion at the surface is the determining factor. This Letter
      reports experiments performed in mice showing that these dynamics can, however,
      be changed. By stimulating the immune response, we induced strong neutrophilia
      around the tumor. The neutrophils hindered cell surface diffusion so much that
      they induced new dynamics compatible with the slower quenched-disorder Edwards
      Wilkinson universality class. Important clinical effects were also seen,
      including remarkably high tumor necrosis (around 80%-90% of the tumor), a general
      increase in survival time [the death ratio in the control group is 15.76 times
      higher than in the treated group (equivalent to a Cox's model hazard ratio of
      0.85; 95% confidence interval 0.76-0.95, p=0.004)], and even the total
      elimination of some tumors.

PMID- 15245197
TI  - Structure of autocatalytically branched actin solutions.
AB  - The average branching number and cluster size in branched actin solutions with
      filament capping are evaluated using analytic theory and simulation methods. The
      average number of daughter branches per filament in steady state is much less
      than unity, regardless of the concentration of branching stimulant. Much more
      highly branched structures are obtained in the initial stages of polymerization.

PMID- 15245198
TI  - Dynamical motifs: building blocks of complex dynamics in sparsely connected
      random networks.
AB  - Spatiotemporal network dynamics is an emergent property of many complex systems
      that remains poorly understood. We suggest a new approach to its study based on
      the analysis of dynamical motifs-small subnetworks with periodic and chaotic
      dynamics. We simulate randomly connected neural networks and, with increasing
      density of connections, observe the transition from quiescence to periodic and
      chaotic dynamics. This transition is explained by the appearance of dynamical
      motifs in the structure of these networks. We also observe domination of periodic
      dynamics in simulations of spatially distributed networks with local connectivity
      and explain it by the absence of chaotic and the presence of periodic motifs in
      their structure.

PMID- 15245199
TI  - Mechanical restriction versus human overreaction triggering congested traffic
      states.
AB  - A new cellular automaton traffic model is presented. The focus is on mechanical
      restrictions of vehicles realized by limited acceleration and deceleration
      capabilities. These features are incorporated into the model in order to
      construct the condition of collision-free movement. The strict collision-free
      criterion imposed by the mechanical restrictions is softened in certain traffic
      situations, reflecting human overreaction. It is shown that the present model
      reliably reproduces most empirical findings including synchronized flow, the so
      called pinch effect, and the time-headway distribution of free flow. The findings
      suggest that many free flow phenomena can be attributed to the platoon formation
      of vehicles (platoon effect).

PMID- 15245200
TI  - Can low-lying Roper states be explained as antidecuplet members?

PMID- 15245201
TI  - Tkachenko oscillations and the compressibility of a rotating Bose-Einstein
      condensate.
AB  - The elastic oscillations of the vortex lattice of a cold Bose gas (Tkachenko
      modes) are shown to play a crucial role in the saturation of the compressibility
      sum rule, as a consequence of the hybridization with the longitudinal degrees of
      freedom. The presence of the vortex lattice is responsible for a q2 behavior of
      the static structure factor at small wave vectors q, which implies the absence of
      long range order in 2D configurations at zero temperature. Sum rules are used to
      calculate the Tkachenko frequency in the presence of harmonic trapping. Results
      are derived in the Thomas-Fermi regime and compared with experiments as well as
      with previous theoretical estimates.

PMID- 15245202
TI  - Bell states of atoms with ultralong lifetimes and their tomographic state
      analysis.
AB  - Arbitrary atomic Bell states with two trapped ions are generated in a
      deterministic and preprogrammed way. The resulting entanglement is quantitatively
      analyzed using various measures of entanglement. For this, we reconstruct the
      density matrix using single qubit rotations and subsequent measurements with near
      unity detection efficiency. This procedure represents the basic building block
      for future process tomography of quantum computations. As a first application,
      the temporal decay of entanglement is investigated in detail. We observe
      ultralong lifetimes for the Bell states Psi(+/-), close to the fundamental limit
      set by the spontaneous emission from the metastable upper qubit level and longer
      than all reported values by 3 orders of magnitude.

PMID- 15245203
TI  - Feshbach resonance induced shock waves in Bose-Einstein condensates.
AB  - We propose a method for generating shock waves in Bose-Einstein condensates by
      rapidly increasing the value of the nonlinear coefficient using Feshbach
      resonances. We show that in a cigar-shaped condensate there exist primary
      (transverse) and secondary (longitudinal) shock waves. We analyze how the shocks
      are generated in multidimensional scenarios and describe the related
      phenomenology.

PMID- 15245204
TI  - BCS-BEC crossover at finite temperature for superfluid trapped Fermi atoms.
AB  - We consider the BCS-BEC (Bose-Einstein-condensate) crossover for a system of
      trapped Fermi atoms at finite temperature, both below and above the superfluid
      critical temperature, by including fluctuations beyond mean field. We determine
      the superfluid critical temperature and the pair-breaking temperature as
      functions of the attractive interaction between Fermi atoms, from the weak- to
      the strong-coupling limit (where bosonic molecules form as bound-fermion pairs).
      Density profiles in the trap are also obtained for all temperatures and
      couplings.

PMID- 15245205
TI  - Exact ground states of rotating Bose gases close to a Feshbach resonance.
AB  - We study the ground states of rotating Bose gases when interactions are affected
      by a nearby Feshbach resonance. We show that exact ground states at high angular
      momentum can be found analytically for a general model for the resonant
      interactions. We identify parameter regimes where the exact ground states are
      exotic fractional quantum Hall states, the excitations of which obey nonabelian
      exchange statistics.

PMID- 15245206
TI  - Mayer sampling: calculation of cluster integrals using free-energy perturbation
      methods.
AB  - Free-energy simulation methods are applied toward the calculation of cluster
      integrals that appear in diagrammatic methods of statistical mechanics. In this
      approach, Monte Carlo sampling is performed on a number of molecules equal to the
      order of the integral, and configurations are weighted according to the absolute
      value of the integrand. An umbrella-sampling average yields the value of the
      cluster integral in reference to a known integral. Virial coefficients, up to the
      sixth for the Lennard-Jones model and the fifth for the SPCE model of water, are
      calculated as a demonstration.

PMID- 15245207
TI  - Tip-enhanced coherent anti-stokes Raman scattering for vibrational nanoimaging.
AB  - An electric field enhanced by a metallic nanoprobe has locally induced coherent
      anti-Stokes Raman scattering (CARS) of adenine molecules in a nanometric DNA
      network structure. Owing to the third-order nonlinearity, the excitation of the
      CARS polarization is extremely confined to the end of the tip apex, resulting in
      a spatial resolution far beyond the diffraction limit of light. Our tip-enhanced
      CARS microscope visualized the DNA network structure at a specific vibrational
      frequency (approximately 1337 cm(-1)) corresponding to the ring-breathing mode of
      diazole of adenine molecules.

PMID- 15245208
TI  - Ultraprecise atomic mass measurement of the alpha particle and 4He.
AB  - The atomic masses of the alpha particle and 4He have been measured by means of a
      Penning trap mass spectrometer which utilizes a frequency-shift detector to
      observe single-ion cyclotron resonances in an extremely stable 6.0 T magnetic
      field. The present resolution of this instrument approaches 0.01 ppb [10 ppt
      (parts per trillion)] and is limited primarily by the effective stability (<5
      ppt/h) of the magnet over hundreds of hours of observation. The leading
      systematic shift [at -202(9) ppt] is due to the image charge located in the trap
      electrodes. The new value for the atomic mass of the alpha particle is 4 001 506
      179.147(64) nu and the corresponding value for the mass of 4He is 4 002 603
      254.153(64) nu (nu=10(-9) u). The 16 ppt uncertainty is at least 20 times smaller
      than any previous determination.

PMID- 15245209
TI  - Covariant information-density cutoff in curved space-time.
AB  - In information theory, the link between continuous information and discrete
      information is established through well-known sampling theorems. Sampling theory
      explains, for example, how frequency-filtered music signals are reconstructible
      perfectly from discrete samples. In this Letter, sampling theory is generalized
      to pseudo-Riemannian manifolds. This provides a new set of mathematical tools for
      the study of space-time at the Planck scale: theories formulated on a
      differentiable space-time manifold can be equivalent to lattice theories. There
      is a close connection to generalized uncertainty relations which have appeared in
      string theory and other studies of quantum gravity.

PMID- 15245210
TI  - Einstein gravity on the codimension 2 brane?
AB  - We look at general brane worlds in six-dimensional Einstein-Gauss-Bonnet gravity.
      We find the general matching conditions for the brane world, which remarkably
      give precisely the four-dimensional Einstein equations for the brane, even when
      the extra dimensions are noncompact and have infinite volume. Relaxing regularity
      of the curvature in the vicinity of the brane, or having a thick brane, gives
      rise to an additional term containing information on the brane's embedding in the
      bulk. We comment on the relevance of these results to a possible solution of the
      cosmological constant problem.

PMID- 15245212
TI  - Neutrino telescopes as a direct probe of supersymmetry breaking.
AB  - We consider models where the scale of supersymmetry breaking lies between 5 x
      10(6) and 5 x 10(8) GeV. In this class of theories, which includes models of
      mediated supersymmetry breaking, the lightest supersymmetric particle is the
      gravitino, and the next to lightest is typically a long-lived charged slepton
      with a lifetime between a microsecond and a second, depending on its mass. We
      investigate the production of these particles by the diffuse flux of high energy
      neutrinos colliding with nucleons in the Earth, and the potential for their
      observation in large ice or water Cerenkov detectors. The small production cross
      section is partially compensated by the very long range of sleptons. The signal,
      two well-separated parallel tracks, has very little background. Using the Waxman
      Bahcall limit for the neutrino flux results in up to four events a year in km3
      experiments.

PMID- 15245214
TI  - Gapless color-flavor-locked quark matter.
AB  - In neutral cold quark matter that is so dense that the strange quark mass Ms is
      unimportant, all three quark flavors pair in a color-flavor locked (CFL) pattern,
      and all nine fermionic quasiparticles have a gap Delta (or 2Delta). We argue
      that, as the density decreases (or Ms increases), there is a quantum phase
      transition (at M(2s/mu approximately 2Delta) to a new "gapless CFL phase" in
      which only seven quasiparticles have a gap. There is still an unbroken U(1)(Q)
      gluon/photon, but, unlike CFL, gapless CFL is a Q conductor with gapless
      (charged) quasiquarks and a nonzero electron density at zero temperature, so its
      low energy effective theory and astrophysical properties are qualitatively new.
      At the transition, the dispersion relations of both gapless quasiparticles are
      quadratic, but for larger M2s/mu, one becomes conventionally linear while the
      other remains quadratic, up to tiny corrections.

PMID- 15245216
TI  - Two-dimensional trapping of dipolar molecules in time-varying electric fields.
AB  - Simultaneous two-dimensional trapping of neutral dipolar molecules in low- and
      high-field seeking states is analyzed. A trapping potential of the order of 20 mK
      can be produced for molecules such as ND3 with time-dependent electric fields.
      The analysis is in agreement with an experiment where slow molecules with
      longitudinal velocities of the order of 20 m/s are guided between four 50 cm long
      rods driven by an alternating electric potential at a frequency of a few kHz.

PMID- 15245217
TI  - Nearest-neighbor-atom core-hole transfer in isolated molecules.
AB  - A new phenomenon sensitive only to next-door-neighbor atoms in isolated molecules
      is demonstrated using angle-resolved photoemission of site-selective core
      electrons. Evidence for this interatomic core-to-core electron interaction is
      observable only by measuring nondipolar angular distributions of photoelectrons.
      In essence, the phenomenon acts as a very fine atomic-scale sensor of nearest
      neighbor elemental identity.

PMID- 15245218
TI  - Propensity rule for novel selective double photoexcitation of helium atoms in
      strong static electric fields.
AB  - We studied the double photoexcitation spectra of helium in a strong dc electric
      field and compared the results with the recent experimental data of Harries et
      al. [Phys. Rev. Lett. 90, 133002 (2003)]]. We derived the propensity rules based
      on the crossing or noncrossing of energies in the Stark map to predict the
      selective subset of doubly excited states that are preferentially populated in
      such experiments. It is shown that the propensity rule is a consequence of the
      ubiquitous correlation properties of doubly excited states in general.

PMID- 15245219
TI  - Quantum feedback control of atomic motion in an optical cavity.
AB  - We study quantum feedback cooling of atomic motion in an optical cavity. We
      design a feedback algorithm that can cool the atom to the ground state of the
      optical potential with high efficiency despite the nonlinear nature of this
      problem. An important ingredient is a simplified state-estimation algorithm,
      necessary for a real-time implementation of the feedback loop. We also describe
      the critical role of parity dynamics in the cooling process and present a simple
      theory that predicts the achievable steady-state atomic energies.

PMID- 15245215
TI  - Observation of the Hadronic transitions chi(b1,2)(2P)-->omegaUpsilon(1S).
AB  - The CLEO Collaboration has made the first observations of hadronic transitions
      among bottomonium (bbmacr;) states other than the dipion transitions among
      Upsilon(nS) states. In our study of Upsilon(3S) decays, we find a significant
      signal for Upsilon(3S)-->gammaomegaUpsilon(1S) that is consistent with radiative
      decays Upsilon(3S)-->gammachi(b1,2)(2P), followed by chi(b1,2)(2P)-
      >omegaUpsilon(1S). The branching ratios we obtain are B[chi(b1)(2P)-
      >omegaUpsilon(1S)]=(1.63(+0.35+0.16)(-0.31-0.15))% and B[chi(b2)(2P)-
      >omegaUpsilon(1S)]=(1.10(+0.32+0.11)(-0.28-0.10))%, in which the first error is
      statistical and the second is systematic.

PMID- 15245220
TI  - Measurement of Cu K-shell and Ag L-shell ionization cross sections by low-energy
      positron impact.
AB  - Inner shell ionization cross sections by low-energy positron impact have been
      measured. Development of an x-ray detector with thin Si(Li) crystals has enabled
      the first measurements of the absolute cross sections for the positron impacts in
      the energy range below 30 keV. Threshold behavior of the measured cross sections
      for the Cu K shell and Ag L shell are compared with the theoretical results of
      Gryzinski and Kowalski [Phys. Lett. A 183, 196 (1993)]] and Khare and Wadehra
      [Can. J. Phys. 74, 376 (1996)]]. Good agreement has been found for the Cu K
      shell, while the experimental values for the Ag L shell were found to be smaller
      than the corresponding theoretical results.

PMID- 15245221
TI  - Practical means for the study of electron correlation in atoms.
AB  - Electron correlation is basic to the understanding of a diverse range of physical
      and chemical phenomena, yet, there have been no direct measurements of the
      correlated motion of electrons. Measurement of the correlated momenta of atomic
      electrons is possible via electron-impact double ionization provided that the
      ionizing collisions are both impulsive and binary, and the three-body scattering
      mechanism is known. The results reported here satisfy these conditions, and a
      practical means for the study of atomic electron correlation through measurement
      of two-electron momentum densities is presented.

PMID- 15245222
TI  - Raman spectroscopy of small para-H2 clusters formed in cryogenic free jets.
AB  - Small para-H2 clusters (pH2)N with N=2,...,8 have been identified by Raman
      spectroscopy in cryogenic free jets of the pure gas, near the Q(0) Raman line of
      the H2 monomer. The high resolution in space, time, and number size makes it
      possible to follow their growth kinetics with distance from the orifice. At lower
      source temperatures liquid clusters appear early in the expansion and then
      undergo a gradual phase transition to the solid state. The technique is very
      promising for exploring superfluidity in pure (pH2)N clusters.

PMID- 15245211
TI  - Search for narrow tt resonances in pp collisions at square root of (s)=1.8 TeV.
AB  - A search for narrow resonances that decay into tt pairs has been performed using
      130 pb(-1) of data in the lepton + jets channel collected by the Dphi detector in
      pp collisions at square root of (s)=1.8 TeV. There is no significant deviation
      observed from the standard-model predictions at a top-quark mass of 175 GeV/c2.
      We therefore present upper limits at the 95% confidence level on the product of
      the production cross section and branching fraction to tt for narrow resonances
      as a function of the resonance mass MX. These limits are used to exclude the
      existence of a leptophobic top-color particle with mass MX<560 GeV/c2, using a
      theoretical cross section for a width GammaX=0.012MX.

PMID- 15245223
TI  - Kapitza-Dirac diffraction without standing waves: diffraction without a grating?
AB  - We discuss electron diffraction from two counterpropagating light waves with two
      different frequencies. We show that, even though these waves do not form a
      standing wave, electron diffraction similar to the conventional Kapitza-Dirac
      effect, i.e., scattering on a standing wave, is still possible. The nonlinear
      response of the electron to the laser fields creates a stationary diffraction
      grating from which the same electron scatters.

PMID- 15245224
TI  - Forces between a single atom and its distant mirror image.
AB  - An excited-state atom whose emitted light is backreflected by a distant mirror
      can experience trapping forces, because the presence of the mirror modifies both
      the electromagnetic vacuum field and the atom's own radiation reaction field. We
      demonstrate this mechanical action using a single trapped barium ion. We observe
      the trapping conditions to be notably altered when the distant mirror is
      translated across an optical wavelength. The well-localized barium ion enables
      the spatial dependence of the forces to be measured explicitly. The experiment
      has implications for quantum information processing and may be regarded as the
      most elementary optical tweezers.

PMID- 15245225
TI  - Random-phase solitons in nonlinear periodic lattices.
AB  - We predict the existence of random phase solitons in nonlinear periodic lattices.
      These solitons exist when the nonlinear response time is much longer than the
      characteristic time of random phase fluctuations. The intensity profiles, power
      spectra, and statistical (coherence) properties of these stationary waves conform
      to the periodicity of the lattice. The general phenomenon of such solitons is
      analyzed in the context of nonlinear photonic lattices.

PMID- 15245226
TI  - Observation of resonance soliton trapping due to a photoinduced gap in wave
      number.
AB  - We investigate the nonlinear propagation of two forward propagating modes coupled
      by a resonant traveling-wave grating, which is photoinduced by illuminating an
      optical fiber with a beat signal. This interaction, representative of systems
      whose dispersion relation K=K(Omega) exhibits a gap in momentum K, shows evidence
      of localization mediated by resonance solitons. The signature of a still (in the
      grating frame) soliton is grating-induced cancellation of modal group-velocity
      mismatch.

PMID- 15245227
TI  - Multifractal clustering in compressible flows.
AB  - A quantitative relationship is found between the multifractal properties of the
      asymptotic mass distribution in a random dissipative system and the long-time
      fluctuations of the local stretching rates of the dynamics. It captures
      analytically the fine aspects of the strongly intermittent clustering of
      dynamical trajectories. Applied to a simple compressible hydrodynamical model
      with known stretching-rate statistics, the relation produces a nontrivial
      spectrum of multifractal dimensions that is confirmed numerically.

PMID- 15245228
TI  - Periodic knolls and valleys: coexistence of solid and liquid states in granular
      suspensions.
AB  - We report the spontaneous emergence of a doubly periodic train of sedimented
      knolls in a dense suspension. These solidified knolls rise out of, and coexist
      alongside, a sea of freely flowing liquid in a slowly rotating horizontal bottle.
      We apply a variable viscosity model that permits simultaneous analysis of
      fluidlike and solidlike behaviors that are ubiquitous in a variety of sedimenting
      flows. The model generates qualitative agreement with experiments, and produces
      new insights into mechanisms by which sedimented structures form.

PMID- 15245229
TI  - Proposal for intense attosecond radiation from an x-ray free-electron laser.
AB  - We propose the use of an ultrarelativistic electron beam interacting with a few
      cycle, intense laser pulse and an intense pulse of the coherent x rays to produce
      a multi-MW intensity, x-ray pulses approximately 100 attoseconds in duration.
      Because of a naturally occurring frequency chirp, these pulses can be further
      temporally compressed.

PMID- 15245231
TI  - Multiple filamentation of terawatt laser pulses in air.
AB  - The filamentation of femtosecond light pulses in air is numerically and
      experimentally investigated for beam powers reaching several TW. Beam propagation
      is shown to be driven by the interplay between intense, robust spikes created by
      the defects of the input beam and random nucleation of light cells. Evolution of
      the filament patterns can be qualitatively reproduced by an averaged-in-time
      (2D+1)-dimensional model derived from the propagation equations for ultrashort
      pulses.

PMID- 15245230
TI  - Observation of laser driven supercritical radiative shock precursors.
AB  - We present a supercritical radiative shock experiment performed with the LULI
      nanosecond laser facility. Using targets filled with xenon gas at low pressure,
      the propagation of a strong shock with a radiative precursor is evidenced. The
      main measured shock quantities (electronic density and propagation velocity) are
      shown to be in good agreement with theory and numerical simulations.

PMID- 15245232
TI  - Kink instability in applied-field magneto-plasma-dynamic thrusters.
AB  - Measurements of magnetic and electrostatic fluctuations in an applied field
      magneto-plasma-dynamic thruster have shown that a m/n=1/1 kink mode becomes
      unstable whenever the Kruskal-Shafranov limit is violated. A positive correlation
      is established between the kink and performance degradation at high current,
      which has until now prevented the use of this kind of thruster in space missions.

PMID- 15245233
TI  - Exact maximal height distribution of fluctuating interfaces.
AB  - We present an exact solution for the distribution P(h(m),L) of the maximal height
      h(m) (measured with respect to the average spatial height) in the steady state of
      a fluctuating Edwards-Wilkinson interface in a one dimensional system of size L
      with both periodic and free boundary conditions. For the periodic case, we show
      that P(h(m),L)=L(-1/2)f(h(m)L(-1/2)) for all L>0, where the function f(x) is the
      Airy distribution function that describes the probability density of the area
      under a Brownian excursion over a unit interval. For the free boundary case, the
      same scaling holds, but the scaling function is different from that of the
      periodic case. Numerical simulations are in excellent agreement with our
      analytical results. Our results provide an exactly solvable case for the
      distribution of extremum of a set of strongly correlated random variables.

PMID- 15245234
TI  - Hallmark of perfect graphene.
AB  - Using first-principles calculations we show that the adsorption of atomic
      hydrogen on graphene opens a substantial gap in the electronic density of states
      in which lies a spin-polarized gap state. This spin is quenched by the presence
      of a rotated C-C bond (a Stone-Wales defect) adjacent to or distant from the H
      atom. We explain these findings and discuss the implications for nanotubes and
      magnetic nanographene. Furthermore, we demonstrate that the combined effect of
      high curvature and a Stone-Wales defect makes H2 chemisorption close to being
      thermodynamically favorable.

PMID- 15245235
TI  - Self-organized quantum-wire lattice via step flow growth of a short-period
      superlattice.
AB  - We develop a theoretical model for step flow growth of multilayer films, taking
      into account the interlayer step-step interaction induced by misfit strain. We
      apply the model to simulate the growth of strain-compensated short-period
      superlattices. Step-bunch ordering improves in successive layers, leading to self
      organized growth of a lattice of quantum wires. This quantum-wire array has some
      similarities to the "lateral composition modulation" observed experimentally in
      short-period superlattices.

PMID- 15245213
TI  - Search for the rare leptonic decay B+-->mu(+)nu(mu).
AB  - We have performed a search for the rare leptonic decay B+-->mu(+)nu(mu) with data
      collected at the Upsilon(4S) resonance by the BABAR experiment at the PEP-II
      storage ring. In a sample of 88.4 x 10(6) BB pairs, we find no significant
      evidence for a signal and set an upper limit on the branching fraction B(B+-
      >my(+)nu(my))< 6.6 x 10(-6) at the 90% confidence level.

PMID- 15245236
TI  - Density functional theory calculations establish the experimental evidence of the
      DX center atomic structure in CdTe.
AB  - The In DX center and the DX-like configuration of the Cd host atom in CdTe are
      investigated using density functional theory. The simultaneous calculation of the
      atomic structure and the electric field gradient (EFG) allows one to correlate
      the theoretically predicted structure of the DX center with an experimental
      observable, namely, the EFG obtained from radioactive 111In/111Cd probe atoms in
      In doped CdTe. In this way, the experimental identification of the DX center
      structure is established.

PMID- 15245237
TI  - Beta relaxation versus high frequency wing in the dielectric spectra of a binary
      molecular glass former.
AB  - The binary molecular glass former 2-picoline in tri-styrene is investigated by
      means of broadband dielectric spectroscopy with the aim of understanding the role
      of secondary relaxation processes that emerge during the glass transition. It is
      shown that the "high frequency wing," which is seen in neat picoline, becomes a
      separate process in the mixture and exhibits all the features of a Johari
      Goldstein relaxation. In particular, the previously found relation between
      activation energy and Tg is recovered. In addition, below Tg the width parameter
      of this secondary relaxation is shown to be governed by a common temperature
      dependence, and the time scale is characterized by an isokinetic point. Above Tg
      pronounced deviations from an Arrhenius behavior are observed.

PMID- 15245238
TI  - Polyamorphism of ice at low temperatures from constant-pressure simulations.
AB  - We report results of molecular dynamics simulations of amorphous ice in the
      pressure range 0-22.5 kbar. The high-density amorphous (HDA) ice prepared by
      compression of Ih ice at T=80 K is annealed to T=170 K at intermediate pressures
      in order to generate relaxed states. We confirm the existence of recently
      observed phenomena, the very high-density amorphous ice, and a continuum of HDA
      forms. We suggest that both phenomena have their origin in the evolution of the
      network topology of the annealed HDA phase with decreasing volume, resulting at
      low temperatures in the metastability of a range of densities.

PMID- 15245239
TI  - Is there a reentrant glass in binary mixtures?
AB  - By employing computer simulations for a model binary mixture, we show that a
      reentrant glass transition upon adding a second component occurs only if the
      ratio alpha of the short-time mobilities between the glass-forming component and
      the additive is sufficiently small. For alpha approximately 1, there is no
      reentrant glass, even if the size asymmetry between the two components is large,
      in accordance with the two-component mode-coupling theory. For alpha<<1, on the
      other hand, the reentrant glass is observed and reproduced only by an effective
      one-component mode-coupling theory.

PMID- 15245240
TI  - Atom movement in In3La studied via nuclear quadrupole relaxation.
AB  - Jump frequencies of Cd tracer atoms in In3La were measured via nuclear quadrupole
      relaxation caused by stochastic reorientation of the electric field gradient
      using the method of perturbed angular correlation of gamma rays. Activation
      enthalpies of 0.53(1) and 0.81(1) eV were found at the two phase boundaries,
      which differ in composition by only about 0.1 at. %. The jump frequency was found
      to be higher at the more In-rich phase boundary, ruling out a simple In-vacancy
      diffusion mechanism. Possible diffusion mechanisms and general applicability of
      the method are discussed.

PMID- 15245241
TI  - Spin susceptibility of two-dimensional electrons in narrow AlAs quantum wells.
AB  - We report measurements of the spin susceptibility in dilute two-dimensional
      electrons confined to a 45 A wide AlAs quantum well. The electrons in this well
      occupy an out-of-plane conduction-band valley, rendering a system similar to two
      dimensional electrons in Si-MOSFETs but with only one valley occupied. We observe
      an enhancement of the spin susceptibility over the band value that increases as
      the density is decreased, following closely the prediction of quantum Monte Carlo
      calculations and continuing at finite values through the metal-insulator
      transition.

PMID- 15245242
TI  - Cluster dynamical mean field analysis of the mott transition.
AB  - We investigate the Mott transition using a cluster extension of dynamical mean
      field theory (DMFT). In the absence of frustration we find no evidence for a
      finite temperature Mott transition. Instead, in a frustrated model, we observe
      signatures of a finite temperature Mott critical point in agreement with
      experimental studies of kappa organics and with single-site DMFT. As the Mott
      transition is approached, a clear momentum dependence of the electron lifetime
      develops on the Fermi surface with the formation of cold regions along the
      diagonal direction of the Brillouin zone. Furthermore, the variation of the
      effective mass is no longer equal to the inverse of the quasiparticle residue, as
      in DMFT, and is reduced approaching the Mott transition.

PMID- 15245243
TI  - Magnetic-field dependence of the anomalous noise behavior in a two-dimensional
      electron system in silicon.
AB  - Studies of low-frequency resistance noise show that the dramatic change in the
      dynamics of the two-dimensional electron system (2DES) in Si that occurs near the
      metal-insulator transition (MIT) persists in high parallel magnetic fields B such
      that the 2DES is fully spin polarized. This strongly suggests that charge, as
      opposed to spin, degrees of freedom are responsible for this effect. In the
      metallic phase, however, noise is suppressed by a parallel B, pointing to the
      role of spins. At low B, the temperature dependence of conductivity in the
      metallic phase provides evidence for a MIT.

PMID- 15245244
TI  - Anisotropic metal-insulator transition in epitaxial thin films.
AB  - By comparing the properties of In and Pb quantum wells in a scanning tunneling
      microscopy subsurface imaging experiment, we found the existence of lateral bound
      states, a 2D Mott-Hubbard correlation gap, induced by transverse confinement. Its
      formation is attributed to spin or charge overscreening of quasi-2D excitations.
      The signature of the 2D confinement-deconfinement transition is also
      experimentally observed, with the correlation gap being pinned in the middle of
      the conduction band. A self-organized 2D Anderson lattice is suggested as a new
      ground state.

PMID- 15245245
TI  - Appearance of fractional charge in the noise of nonchiral Luttinger liquids.
AB  - The current noise of a voltage biased interacting quantum wire adiabatically
      connected to metallic leads is computed in the presence of an impurity in the
      wire. We find that in the weak backscattering limit the Fano factor
      characterizing the ratio between noise and backscattered current crucially
      depends on the noise frequency omega relative to the ballistic frequency vF/gL,
      where vF is the Fermi velocity, g is the Luttinger liquid interaction parameter,
      and L is the length of the wire. In contrast to chiral Luttinger liquids the
      noise is not only due to the Poissonian backscattering of fractionally charged
      quasiparticles at the impurity, but it also depends on Andreev-type reflections
      at the contacts, so that the frequency dependence of the noise needs to be
      analyzed to extract the fractional charge e*=eg of the bulk excitations.

PMID- 15245246
TI  - Auger energy shifts in fcc AgPd random alloys from complete screening picture and
      experiment.
AB  - We extend the complete screening picture to ab initio calculations of Auger
      kinetic energy and Auger parameter shifts in metallic alloys. Experimental
      measurements of the L(3)M(4,5)M(4,5) Auger transition in fcc AgPd random alloys
      are compared with first-principles calculations and the results are in excellent
      agreement for both the Ag and Pd Auger shifts over the whole concentration range.
      We discuss the Auger kinetic energy shifts in terms of single-hole states for the
      2p(3/2) core level and double-hole states for the 3d(5/2) level.

PMID- 15245247
TI  - Shot noise in linear macroscopic resistors.
AB  - We report on direct experimental evidence of shot noise in a linear macroscopic
      resistor. The origin of the shot noise comes from the fluctuation of the total
      number of charge carriers inside the resistor associated with their diffusive
      motion under the condition that the dielectric relaxation time becomes longer
      than the dynamic transit time. The present results show that neither potential
      barriers nor the absence of inelastic scattering are necessary to observe shot
      noise in electronic devices.

PMID- 15245248
TI  - Spin injection in the nonlinear regime: band bending effects.
AB  - We report on electrical spin-injection measurements into a nonmagnetic
      semiconductor in the nonlinear regime. For voltage drops across the interface
      larger than a few mV the spin-injection efficiency decreases strongly. The effect
      is caused by repopulation of the minority spin level in the magnetic
      semiconductor due to band bending at the interface.

PMID- 15245249
TI  - Differential charge sensing and charge delocalization in a tunable double quantum
      dot.
AB  - We report measurements of a tunable double quantum dot, operating in the quantum
      regime, with integrated local charge sensors. The spatial resolution of the
      sensors allows the charge distribution within the double dot system to be
      resolved at fixed total charge. We use this readout scheme to investigate charge
      delocalization as a function of temperature and strength of tunnel coupling,
      demonstrating that local charge sensing can be used to accurately determine the
      interdot coupling in the absence of transport.

PMID- 15245250
TI  - Multimode transport in Schottky-barrier carbon-nanotube field-effect transistors.
AB  - We present a detailed study on the impact of multimode transport in carbon
      nanotube field-effect transistors. Under certain field conditions electrical
      characteristics of tube devices are a result of the contributions of more than
      one one-dimensional subband. Through potassium doping of the nanotube the impact
      of the different bands is made visible. We discuss the importance of scattering
      for a stepwise change of current as a function of gate voltage and explain the
      implications of our observations for the performance of nanotube transistors.

PMID- 15245251
TI  - Imaging phase separation near the Mott boundary of the correlated organic
      superconductors kappa-(BEDT-TTF)2X.
AB  - Electronic phase separation consisting of the metallic and insulating domains
      with 50-100 microm in diameter is found in the organic Mott system kappa-[(h8
      BEDT-TTF)(1-x)(d8-BEDT-TTF)x]2Cu[N(CN)2]Br by means of scanning microregion
      infrared spectroscopy using the synchrotron radiation. The phase separation
      appears below the critical end temperature 35-40 K of the first-order Mott
      transition. The observation of the macroscopic size of the domains indicates a
      different class of the intrinsic electronic inhomogeneity from the nanoscale one
      reported in the inorganic Mott systems such as high-Tc copper and manganese
      oxides.

PMID- 15245252
TI  - Enhancement of pairing correlation by t' in the two-dimensional extended t-J
      model.
AB  - We investigate the effects of the next-nearest-neighbor (t') and the third
      nearest-neighbor (t") hopping terms on superconductivity correlation in the 2D
      hole-doped extended t-J model based on the variational Monte Carlo, mean-field
      calculation and exact diagonalization method. Despite the diversity of the
      methods employed, the results all point to a consistent conclusion: While the d
      wave superconductivity correlation is slightly suppressed by t' and t" in
      underdoped regions, it is greatly enhanced in the optimal and overdoped regions.
      The optimal Tc is a result of the balance of these two opposite trends.

PMID- 15245253
TI  - Spin-flop transition and the anisotropic magnetoresistance of Pr(1.3
      x)La(0.7)CexCuO4: unexpectedly strong spin-charge coupling in the electron-doped
      cuprates.
AB  - We use transport and neutron-scattering measurements to show that a magnetic
      field-induced transition from noncollinear to collinear spin arrangement in
      adjacent CuO2 planes of lightly electron-doped Pr(1.3-x)La(0.7)CexCuO4 (x=0.01)
      crystals affects significantly both the in-plane and out-of-plane resistivity. In
      the high-field collinear state, the magnetoresistance (MR) does not saturate but
      exhibits an intriguing fourfold-symmetric angular dependence, oscillating from
      being positive at B//[100] to being negative at B//[110]. The observed MR of more
      than 30% at low temperatures induced by a modest modification of the spin
      structure indicates an unexpectedly strong spin-charge coupling in electron-doped
      cuprates.

PMID- 15245255
TI  - Orbital ordering, new phases, and stripe formation in doped layered nickelates.
AB  - Ground-state properties of layered nickelates are investigated based on the
      orbital-degenerate Hubbard model coupled with lattice distortions, by using
      numerical techniques. The Neel state composed of spin S=1 ions is confirmed in
      the undoped limit x = 0. At x = 1/2, novel antiferromagnetic states, called CE-
      and E-type phases, are found by increasing the Hund's coupling. (3x2-r2/3y2-r2)
      type orbital ordering is predicted to occur in a checkerboard-type charge-ordered
      state. At x = 1/3, both Coulombic and phononic interactions are found to be
      important, since the former stabilizes the spin stripe, while the latter leads to
      the striped charge order.

PMID- 15245254
TI  - Observation of the vortex lattice spinodal in NbSe2.
AB  - Metastable superheated and supercooled vortex states in NbSe2 crystals were
      probed with fast transport measurements over a wide range of field and
      temperature. The limit of metastability of the superheated vortex lattice defines
      a line in the phase diagram that lies below the superconducting transition and is
      clearly separated from it. This line is identified as the vortex lattice
      spinodal, and is in good agreement with recent theoretical predictions by Li and
      Rosenstein [Phys. Rev. B 65, 220504 (2002)]; cond-mat/0305258]. By contrast, no
      limit of metastability is observed for the supercooled disordered state.

PMID- 15245256
TI  - Hydrogen control of ferromagnetism in a dilute magnetic semiconductor.
AB  - We show that upon exposure to a remote dc hydrogen plasma, the magnetic and
      electronic properties of the dilute magnetic semiconductor Ga1-xMnxAs change
      qualitatively. While the as-grown Ga1-xMnxAs thin films are ferromagnetic at
      temperatures T less, similar 70 K, the samples are found to be paramagnetic after
      the hydrogenation, with a Brillouin-type magnetization curve even at T=2 K.
      Comparing magnetization and electronic transport measurements, we conclude that
      the density of free holes p is significantly reduced by the plasma process, while
      the density of Mn magnetic moments does not change.

PMID- 15245257
TI  - Return to return point memory.
AB  - We describe a new class of systems exhibiting return point memory (RPM),
      different from those discussed before in the context of ferromagnets. We show
      numerically that one-dimensional random Ising antiferromagnets have exact RPM
      when evolving from a large field, but not when started at finite field, unlike
      the ferromagnetic case. This implies that the standard approach to understanding
      ferromagnetic RPM will fail for this case. We also demonstrate RPM with a set of
      variables that keeps track of spin flips at each site. Conventional RPM for the
      spins is a projection of this result, suggesting that spin flip variables might
      be a more fundamental representation of the dynamics. We also present a mapping
      that embeds the antiferromagnetic chain in a two-dimensional ferromagnet, and
      prove RPM for spin-exchange dynamics in the interior of the chain with this
      mapping.

PMID- 15245258
TI  - Two-photon coherent control of a single quantum dot.
AB  - We report on two-photon coherent control of the biexciton state in single
      Stranski-Krastanov CdSe quantum dots. Clear interference patterns are observed at
      twice the optical frequency. The decay of the interference contrast is
      nonexponential and caused by a dynamical inhomogeneous broadening of the energy
      levels due to long-term fluctuations in the dot environment.

PMID- 15245259
TI  - All-optical subpicosecond magnetic switching in NiO(001).
AB  - Combining optical control theory with ab initio quantum chemistry and electronic
      crystal field theory we explore the laser induced femtosecond spin dynamics. We
      propose a scenario for ultrafast all-optical magnetic switching that results from
      the combination of spin-orbit coupling with appropriately shaped short laser
      pulses. We find that the application of the theory to the multiplet states within
      the gap of NiO(001) predicts for the first time the possibility of all-optical
      spin switching within 100 fs. The switching can be observed using any of the
      multiplets as the intermediate state.

PMID- 15245260
TI  - DNA spools under tension.
AB  - DNA spools, structures in which DNA is wrapped and helically coiled onto itself
      or onto a protein core, are ubiquitous in nature. We develop a general theory
      describing the nonequilibrium behavior of DNA spools under linear tension. Two
      puzzling and seemingly unrelated recent experimental findings, the sudden
      quantized unwrapping of nucleosomes and that of DNA toroidal condensates under
      tension, are theoretically explained and shown to be of the same origin. The
      study provides new insights into nucleosome and chromatin fiber stability and
      dynamics.

PMID- 15245261
TI  - Hidden symmetry in chains of biological coupled oscillators.
AB  - We experimentally investigated spatiotemporal patterns in chains of coupled
      biological oscillators with boundaries and found hidden symmetric patterns that
      are not straightforwardly derived from explicit geometrical symmetry of the
      systems. We propose a model of coupled oscillators in chains with a hidden
      oscillator interconnecting its boundaries. The model can explain all observed
      patterns including the hidden symmetric ones, while other models such as discrete
      analogs of Neumann boundary conditions in continuous systems cannot.

PMID- 15245262
TI  - Population dynamics with global regulation: the conserved Fisher equation.
AB  - We introduce and study a conserved version of the Fisher equation. Within a
      population biology context, this model describes spatially extended populations
      in which the total number of individuals is fixed due to either biotic or
      environmental factors. We find a rich spectrum of dynamical phases including a
      pseudotraveling wave and, in the presence of the Allee effect, a phase transition
      from a locally constrained high density state to a low density fragmented state.

PMID- 15245263
TI  - Do earthquakes exhibit self-organized criticality?
AB  - If earthquakes are phenomena of self-organized criticality (SOC), statistical
      characteristics of the earthquake time series should be invariant after the
      sequence of events in an earthquake catalog are randomly rearranged. In this
      Letter we argue that earthquakes are unlikely phenomena of SOC because our
      analysis of the Southern California Earthquake Catalog shows that the first
      return-time probability PM(T) is apparently changed after the time series is
      rearranged. This suggests that the SOC theory should not be used to oppose the
      efforts of earthquake prediction.

PMID- 15245264
TI  - Weighted evolving networks: coupling topology and weight dynamics.
AB  - We propose a model for the growth of weighted networks that couples the
      establishment of new edges and vertices and the weights' dynamical evolution. The
      model is based on a simple weight-driven dynamics and generates networks
      exhibiting the statistical properties observed in several real-world systems. In
      particular, the model yields a nontrivial time evolution of vertices' properties
      and scale-free behavior for the weight, strength, and degree distributions.

PMID- 15245265
TI  - Exact decoherence to pointer states in free open quantum systems is universal.
AB  - In this Letter it is shown that exact decoherence to minimal uncertainty Gaussian
      pointer states is generic for free quantum particles coupled to a heat bath. More
      specifically, the Letter is concerned with damped free particles linearly coupled
      under product initial conditions to a heat bath at arbitrary temperature, with
      arbitrary coupling strength and spectral densities covering the Ohmic, sub-Ohmic,
      and supra-Ohmic regime. Then it is true that there exists a time t(c) such that
      for times t>t(c) the state can always be exactly represented as a mixture (convex
      combination) of particular minimal uncertainty Gaussian states, regardless of and
      independent from the initial state. This exact "localization" is hence not a
      feature specific to high temperature and weak damping limit, but is a generic
      property of damped free particles.

PMID- 15245266
TI  - Observation of half-quantum defects in superfluid 3He-B.
AB  - In the course of high-precision measurements of the relation between the
      superflow current J through a weak link in 3He-B and the difference in order
      parameter phase between each side of the link phi in a flexible wall Helmholtz
      resonator equipped with a rotation pickup loop, we have observed the signature of
      a stable textural defect that sustains a change of the phase by pi across it.
      "Cosmiclike" solitons, proposed by Salomaa and Volovik and hitherto thought
      unstable, can constitute such a defect.

PMID- 15245267
TI  - Realization of the Einstein-Podolsky-Rosen paradox using momentum- and position
      entangled photons from spontaneous parametric down conversion.
AB  - We report on a momentum-position realization of the EPR paradox using direct
      detection in the near and far fields of the photons emitted by collinear type-II
      phase-matched parametric down conversion. Using this approach we achieved a
      measured two-photon momentum-position variance product of 0.01 variant Planck's
      over 2pi (2), which dramatically violates the bounds for the EPR and separability
      criteria.

PMID- 15245268
TI  - Evolution of wave-packet spread under sequential scattering of particles of
      unequal mass.
AB  - Under assumptions on initial wave-packet spreads and particle interactions,
      different mass particles scattering off one another will have the product
      sigma(2)(i)m(i) converge to a common value, where sigma(i) is the spread and m(i)
      is the mass of the ith particle. When this relation is satisfied, kinematic
      entanglement vanishes.

PMID- 15245269
TI  - Continuous melting of compact polymers.
AB  - The competition between chain entropy and bending rigidity in compact polymers
      can be addressed within a lattice model introduced by Flory in 1956 [Proc. R.
      Soc. London A 234, 60 (1956)]]. It exhibits a transition between an entropy
      dominated disordered phase and an energetically favored crystalline phase. The
      nature of this order-disorder transition has been debated ever since the
      introduction of the model. Here we present exact results for the Flory model in
      two dimensions relevant for polymers on surfaces, such as DNA adsorbed on a lipid
      bilayer. We predict a continuous melting transition and compute exact values of
      critical exponents at the transition point.

PMID- 15245270
TI  - Numerical simulation of orbiting black holes.
AB  - We present numerical simulations of binary black hole systems which for the first
      time last for about one orbital period for close but still separate black holes
      as indicated by the absence of a common apparent horizon. An important part of
      the method is the construction of comoving coordinates, in which both the angular
      and the radial motion are minimized through a dynamically adjusted shift
      condition. We use fixed mesh refinement for computational efficiency.

PMID- 15245271
TI  - Deflagrations and detonations in thermonuclear supernovae.
AB  - We study a type Ia supernova explosion using three-dimensional numerical
      simulations based on reactive fluid dynamics. We consider a delayed-detonation
      model that assumes a deflagration-to-detonation transition. In contrast with the
      pure deflagration model, the delayed-detonation model releases enough energy to
      account for a healthy explosion, and does not leave carbon, oxygen, and
      intermediate-mass elements in central parts of a white dwarf. This removes the
      key disagreement between simulations and observations, and makes a delayed
      detonation the mostly likely mechanism for type Ia supernovae.

PMID- 15245272
TI  - Measuring the small-scale power spectrum of cosmic density fluctuations through
      21 cm tomography prior to the epoch of structure formation.
AB  - The thermal evolution of the cosmic gas decoupled from that of the cosmic
      microwave background (CMB) at a redshift z approximately 200. Afterwards and
      before the first stars had formed, the cosmic neutral hydrogen absorbed the CMB
      flux at its resonant 21 cm spin-flip transition. We calculate the evolution of
      the spin temperature for this transition and the resulting anisotropies that are
      imprinted on the CMB sky due to linear density fluctuations during this epoch.
      These anisotropies, at an observed wavelength of 10.56[(1+z)/50] m, contain an
      amount of information that is orders of magnitude larger than any other
      cosmological probe.

PMID- 15245273
TI  - Dynamical approach to the cosmological constant.
AB  - We consider a dynamical approach to the cosmological constant. There is a scalar
      field with a potential whose minimum occurs at a generic, but negative, value for
      the vacuum energy, and it has a nonstandard kinetic term whose coefficient
      diverges at zero curvature as well as the standard kinetic term. Because of the
      divergent coefficient of the kinetic term, the lowest energy state is never
      achieved. Instead, the cosmological constant automatically stalls at or near
      zero. The merit of this model is that it is stable under radiative corrections
      and leads to stable dynamics, despite the singular kinetic term. The model is not
      complete, however, in that some reheating is required. Nonetheless, our approach
      can at the very least reduce fine-tuning by 60 orders of magnitude or provide a
      new mechanism for sampling possible cosmological constants and implementing the
      anthropic principle.

PMID- 15245274
TI  - In-medium effects on charmonium production in heavy-ion collisions.
AB  - Charmonium production in heavy-ion collisions is investigated within a kinetic
      theory framework incorporating in-medium properties of open- and hidden-charm
      states in line with recent QCD lattice calculations. A continuously decreasing
      open-charm threshold across the phase boundary of hadronic and quark-gluon matter
      is found to have important implications for the equilibrium abundance of
      charmonium states. The survival of J/psi resonance states above the transition
      temperature enables their recreation also in the quark-gluon plasma. Including
      effects of chemical and thermal off-equilibrium, we compare our model results to
      available experimental data at CERN SPS and BNL RHIC energies. In particular,
      earlier found discrepancies in the psi(')/psi ratio can be resolved.

PMID- 15245275
TI  - Quantum phase transitions in mesoscopic systems.
AB  - Quantum phase transitions in mesoscopic systems are studied. It is shown that the
      main features of phase transitions, defined for infinite number of particles, N-
      > infinity, persist even for moderate N approximately 10. A Landau analysis of
      first order transitions is done and a "critical" exponent at the spinodal point
      is defined. Two order parameters are introduced to distinguish first from second
      order transitions. Applications to atomic nuclei, molecules, atomic clusters, and
      finite polymers are mentioned. Experimental evidence in atomic nuclei is
      presented.

PMID- 15245276
TI  - Relativistic and QED corrections for the beryllium atom.
AB  - Complete relativistic and quantum electrodynamics corrections of order alpha(2)
      Ry and alpha(3) Ry are calculated for the ground state of the beryllium atom and
      its positive ion. A basis set of correlated Gaussian functions is used, with
      exponents optimized against nonrelativistic binding energies. The results for
      Bethe logarithms ln(k(0)(Be)=5.750 34(3) and ln(k(0)(Be+)=5.751 67(3) demonstrate
      the availability of high precision theoretical predictions for energy levels of
      the beryllium atom and light ions. Our recommended value of the ionization
      potential 75 192.514(80) cm(-1) agrees with equally accurate available
      experimental values.

PMID- 15245277
TI  - Fully differential rates for femtosecond multiphoton double ionization of neon.
AB  - We have investigated the full three-dimensional momentum correlation between the
      electrons emitted from strong field double ionization of neon when the
      recollision energy of the first electron is on the order of the ionization
      potential. The momentum correlation in the direction perpendicular to the laser
      field depends on the time difference of the two electrons leaving the ion. Our
      results are consistent with double ionization proceeding through transient double
      excited states that field ionize.

PMID- 15245278
TI  - Energy loss by keV ions in silicon.
AB  - Using silicon photodiodes with an ultrathin passivation layer, the average total
      energy lost to silicon target electrons (electronic stopping) by incident low
      energy ions and the recoil target atoms they generate is directly measured. We
      find that the total electronic energy deposition and the ratio of the total
      nuclear to electronic stopping powers for the incident ions and their recoils
      each follow a simple, universal representation, thus enabling systematic
      prediction of ion-induced effects in silicon. We also observe a velocity
      threshold at 0.05 a.u. for the onset of electronic stopping.

PMID- 15245279
TI  - Mutual projectile-target ionization via the two-center dielectronic interaction
      in relativistic ion-atom collisions.
AB  - We study mutual ionization in relativistic collisions between hydrogenlike
      projectiles and helium atoms: X(Z+)(1s)+He(1s(2))-->X((Z+1)+)+ He+(1s)+2e(-). At
      high collision velocities and for not too heavy projectiles, 2Z/v<<1 (v is the
      collision velocity), the mutual ionization proceeds via the direct interaction
      between two electrons bound (initially) to different colliding particles.
      Considering for the first time this fundamental process in the case of
      relativistic collisions, we calculate ionization cross sections and discuss
      manifestations of relativistic effects. In particular, we predict two novel and
      interesting phenomena: (i) considerable relativistic effects in collisions with
      low Lorentz factors gamma and (ii) the rapid saturation of these effects at
      higher gamma. Estimates show that the predicted effects can be experimentally
      tested using existing facilities and spectrometers.

PMID- 15245280
TI  - Single-photon generation from stored excitation in an atomic ensemble.
AB  - Single photons are generated from an ensemble of cold Cs atoms via the protocol
      of Duan et al. [Nature (London), ()]]. Conditioned upon an initial detection from
      field 1 at 852 nm, a photon in field 2 at 894 nm is produced in a controlled
      fashion from excitation stored within the atomic ensemble. The single-quantum
      character of field 2 is demonstrated by the violation of a Cauchy-Schwarz
      inequality, namely w(1(2),1(2)|1(1))=0.24+/-0.05 not > or = 1, where
      w(1(2),1(2)|1(1)) describes the detection of two events (1(2),1(2)) conditioned
      upon an initial detection 1(1), with w-->0 for single photons.

PMID- 15245281
TI  - Chaos in practically isolated microcavity lasers.
AB  - We report that essentially isolated microcavity lasers may interact in the most
      complicated manner and drive each other chaotic. As the optical isolation between
      these lasers reaches presently practically attainable limits, instead of
      approaching independent operation, the lasers exhibit mutually induced chaotic
      oscillations. The chaos arises from an intricate coupling of the nonlinearities
      associated with coupled optical resonators and those evolving from the population
      dynamics in the active region. The investigation is performed using a composite
      cavity theory and a class-B description of the gain medium. Bifurcation analysis
      identifies the source of instabilities and determines their robustness.

PMID- 15245282
TI  - Self-similar evolution of parabolic pulses in a laser.
AB  - Self-similar propagation of ultrashort, parabolic pulses in a laser resonator is
      observed theoretically and experimentally. This constitutes a new type of pulse
      shaping in mode-locked lasers: in contrast to the well-known static (solitonlike)
      and breathing (dispersion-managed soliton) pulse evolutions, asymptotic solutions
      to the nonlinear wave equation that governs pulse propagation in most of the
      laser cavity are observed. Stable self-similar pulses exist with energies much
      greater than can be tolerated in solitonlike pulse shaping, and this has
      implications for practical lasers.

PMID- 15245283
TI  - Beyond the diffusing-wave spectroscopy model for the temporal fluctuations of
      scattered light.
AB  - We extend the theory of diffusing-wave spectroscopy using a random-walk approach
      and a numerical solution of the radiative transfer equation. The theory is not
      restricted to the diffusive regime and allows one to describe the crossover
      between the single-scattering and the diffusive regimes, which has been observed
      experimentally. It also predicts a lower bound of the scattered-field correlation
      time at long paths. This extended theory should have broad experimental
      applications in the field of imaging through biological tissues.

PMID- 15245284
TI  - Shear band formation in granular media as a variational problem.
AB  - Strain in sheared dense granular material is often localized in a narrow region
      called the shear band. Recent experiments in a modified Couette cell provided
      localized shear flow in the bulk away from the confining walls. The nontrivial
      shape of the shear band was measured as the function of the cell geometry. First,
      we present a geometric argument for narrow shear bands that connects the function
      of their surface position with the shape in the bulk. Assuming a simple
      dissipation mechanism, we show that the principle of minimum dissipation of
      energy provides a good description of the shape function. Furthermore, we discuss
      the possibility and behavior of shear bands that are detached from the free
      surface and are entirely covered in the bulk.

PMID- 15245285
TI  - Beam-beam limit in e+e- circular colliders.
AB  - Beam-beam effects limit the luminosity of circular colliders. Once the bunch
      population exceeds a threshold, the luminosity increases at a slower rate. This
      phenomenon is called the beam-beam limit. Onset of the beam-beam limit has been
      analyzed with various simulation methods based on the weak-strong and strong
      strong models. We have observed that an incoherent phenomenon is mainly concerned
      in the beam-beam limit. The simulation have shown that equilibrium distributions
      of the two colliding beams are distorted from Gaussians when the luminosity is
      limited. The beam-beam limit is estimated to be xi approximately 0.1 for a B
      factory with damping time of several thousand turns.

PMID- 15245286
TI  - Nature of the isotope effect on transport in tokamaks.
AB  - The reduction of energy and particle losses with the increasing mass of the
      hydrogen isotope is more pronounced under conditions of improved confinement when
      the dominant ion temperature gradient instability is suppressed and other
      channels of anomalous transport are of importance. In this Letter, we reconsider
      the dissipative trapped electron (DTE) instability by taking into account finite
      Larmor radius effects in the analysis of the ion response to perturbations. By
      applying the improved mixing length approximation in order to estimate the
      transport coefficients, it is demonstrated that DTE contribution is intrinsically
      dependent on the isotope mass and provides a plausible explanation for the
      isotope effect. Contrary to the common belief, it is shown that the DTE
      turbulence may be of importance for reactor plasmas of low collisionality.

PMID- 15245287
TI  - Quantum size effects in the polarizability of carbon fullerenes.
AB  - We investigate the size-dependent dielectric response of carbon fullerenes with
      up to 3840 atoms in the framework of the linear response theory. Our results
      suggest a significant polarizability enhancement due to quantum size effects with
      respect to classical or semiclassical calculations. The accuracy of our results,
      based on a parametrized Hamiltonian, is verified by ab initio time dependent
      density functional calculations for smaller fullerenes. Our findings underline
      the importance of quantum effects in the electronic response of nano- and
      mesoscopic systems.

PMID- 15245288
TI  - Fracture of silicate glasses: ductile or brittle?
AB  - Atomic force microscopy is used to investigate the possibility of cavity
      formation during crack growth in silicate glasses. Matching areas on both
      fracture surfaces were mapped and then compared. For silica glass, and soda-lime
      silicate glass, the fracture surfaces matched to a resolution of better than 0.3
      nm normal to the surface and 5 nm parallel to the surface. We could find no
      evidence for cavity formation in our study and suggest that completely brittle
      fracture occurs in glass.

PMID- 15245289
TI  - Universality in the vibrational spectra of single-component amorphous clusters.
AB  - We have numerically investigated the vibrational spectra of amorphous single
      component clusters for several types of interactions among the particles. For all
      the potentials we have studied, we find that the density of states can be
      described, except at the two ends of the spectrum, by the same functional form to
      a very good approximation, and that the fluctuation properties of the spectra in
      this central region converge to those of the Gaussian orthogonal ensemble of
      random matrices with increasing system size. We conjecture that this scenario is
      true for a broad class of potentials.

PMID- 15245290
TI  - Harmonic lattice behavior of two-dimensional colloidal crystals.
AB  - Using positional data from videomicroscopy and applying the equipartition theorem
      for harmonic Hamiltonians, we determine the wave-vector-dependent normal mode
      spring constants of a two-dimensional colloidal model crystal and compare the
      measured band structure to predictions of the harmonic lattice theory. We find
      good agreement for both the transversal and the longitudinal modes. For q-->0,
      the measured spring constants are consistent with the elastic moduli of the
      crystal.

PMID- 15245291
TI  - Exceptional ideal strength of carbon clathrates.
AB  - We study by means of ab initio calculations the ideal tensile and shear strengths
      of the C-46 clathrate phase. While its bulk modulus and elastic constants are
      smaller than in diamond, its strength is found to be in all directions larger
      than the critical stresses associated with the diamond [111] planes of easy slip.
      This can be related to the frustration by the clathrate cage structure of the
      diamond to graphite instability under nonhydrostatic stress conditions
      [corrected] The criteria for designing strong materials are discussed.

PMID- 15245292
TI  - Spectroscopic evidence of polymorphism in vitreous B2O3.
AB  - Brillouin and Raman spectroscopy were performed on B2O3 glass compressed to 57
      GPa at 273 K. Upon compression the sound velocities increase smoothly and the
      boroxol ring Raman mode vanishes by 11 GPa. Upon decompression the sound
      velocities follow a different path and at 3 GPa a discontinuity of 3 km/s in V(p)
      and 2 km/s in V(s) returns the velocities to the values seen on compression.
      After the transition, the boroxol ring Raman mode reappears. A second pressure
      cycle produces the same behavior, suggesting the 3 GPa transition occurs between
      vitreous polymorphs with different boron coordination.

PMID- 15245293
TI  - In situ observation of carbon-nanopillar tubulization caused by liquidlike iron
      particles.
AB  - The tubulization process of amorphous carbon nanopillars was observed in situ by
      transmis-sion electron microscopy. Amorphous carbon nanopillars were transformed
      into graphitic tubules by annealing at 650-900 degrees C in the presence of iron
      nanoparticles. A molten catalyst nanoparticle penetrated an amorphous carbon
      nanopillar, dissolving it, and leaving a graphite track behind. An iron
      nanoparticle moved with its shape changing like an earthworm. We concluded that
      the tubulization mechanism is a solid-(quasiliquid)-solid mechanism where the
      carbon phase transformation is a kind of liquid phase graphitization of amorphous
      carbon catalyzed by liquefied metal-carbon alloy nanoparticles.

PMID- 15245294
TI  - Semiconducting surface reconstructions of p-type Si(100) substrates at 5 K.
AB  - We report scanning tunneling microscopy (STM) studies of the technologically
      important Si(100) surface that reveal at 5 K the coexistence of stable surface
      domains consisting of the p(2 x 1) reconstruction along with the c(4 x 2) and p(2
      x 2) reconstructions. Using highly resolved tunneling spectroscopic measurements
      and tight binding calculations, we prove that the p(2 x 1) reconstruction is
      asymmetric and determine the mechanism that enables the contrast variation
      observed in the formation of the bias-dependent STM images for this
      reconstruction.

PMID- 15245295
TI  - Ultrafast laser excitation of CO/Pt(111) probed by sum frequency generation:
      coverage dependent desorption efficiency.
AB  - CO photodesorption from Pt(111) induced by femtosecond laser pulses is probed by
      IR+visible sum frequency generation (SFG). Steady state analysis of SFG spectra
      at varying CO pressure and laser fluence allows one to measure a approximately 5
      orders of magnitude decrease of the photodesorption rate constant when CO
      coverage decreases from 0.37 to 0.07 monolayer. We ascribe this effect in the
      framework of the Menzel-Gomer-Redhead mechanism to electron delocalization in the
      CO layer. The lifetime of electronic excitation decreases when coverage
      decreases.

PMID- 15245296
TI  - Emergence of supersteps on KH2PO4 crystal surfaces.
AB  - In situ AFM investigation of growth on the [100] face of KH2PO4 in the presence
      of Al(III) and other trivalent metals reveals the emergence of a new type of
      morphological feature-the superstep. Supersteps, or step bunches consisting of 50
      1500 elementary steps, are responsible for growth at all supersaturations and
      exhibit behavior not predicted by accepted models. The step velocity of the
      superstep is greater than that of single atomic steps and increases with step
      height. The steepness of the step riser reaches a limiting value of only 11.8
      degrees.

PMID- 15245297
TI  - Critical role of surface steps in the alloying of Ge on Si(001).
AB  - Using low-energy electron microscopy, we show that intermixing of Ge on Si(001)
      during growth is enhanced on stepped surfaces and is hindered on terraces where
      step flow does not occur. On large terraces we have identified a dramatic and
      unanticipated structural rearrangement that facilitates intermixing: Pairs of
      steps spontaneously form and migrate over the surface, leaving alloyed regions in
      their wake. The driving force for step formation is the entropy gain associated
      with the enhanced intermixing of Ge.

PMID- 15245298
TI  - Shear at twin domain boundaries in YBa2Cu3O7-x.
AB  - The microstructure and strain state of twin domains in YBa2Cu3O7-x are discussed
      based upon synchrotron white-beam x-ray microdiffraction measurements. Intensity
      variations of the fourfold twin splitting of Laue diffraction peaks are used to
      determine the twin domain structure. Strain analysis shows that interfaces
      between neighboring twin domains are strained in shear, whereas the interior of
      these domains are regions of low strain. These measurements are consistent with
      the orientation relationships of twin boundaries within and across domains and
      show that basal plane shear stresses can exceed 100 MPa where twin domains meet.
      Our results support stress field pinning of magnetic flux vortices by twin domain
      boundaries.

PMID- 15245299
TI  - Effect of particle-hole asymmetry on the Mott-Hubbard metal-insulator transition.
AB  - The Mott-Hubbard metal-insulator transition is one of the most important problems
      in correlated-electron systems. In the past decade, much progress has been made
      in examining a particle-hole symmetric form of the transition in the Hubbard
      model with dynamical mean field theory, where it was found that the electronic
      self-energy develops a pole at the transition. We examine the particle-hole
      asymmetric metal-insulator transition in the Falicov-Kimball model and find that
      a number of features change when the noninteracting density of states has a
      finite bandwidth.

PMID- 15245300
TI  - Orbital-selective mott transitions in the degenerate Hubbard model.
AB  - We investigate the Mott transitions in two-band Hubbard models with different
      bandwidths. Applying dynamical mean field theory, we discuss the stability of
      itinerant quasiparticle states in each band. We demonstrate that separate Mott
      transitions occur at different Coulomb interaction strengths in general, which
      merge to a single transition only under special conditions. This kind of behavior
      may be relevant for the physics of the single-layer ruthenates, Ca2-xSrxRuO4.

PMID- 15245302
TI  - Climbing the entropy barrier: driving the single- towards the multichannel Kondo
      effect by a weak coulomb blockade of the leads.
AB  - We study a model proposed recently in which a small quantum dot is coupled
      symmetrically to several large quantum dots characterized by a charging energy
      E(c). Even if E(c) is much smaller than the Kondo temperature T(K), the long
      ranged interactions destabilize the single-channel Kondo effect and induce a flow
      towards a multichannel Kondo fixed point associated with a rise of the impurity
      entropy with decreasing temperature. Such an "uphill flow" implies a negative
      impurity specific heat, in contrast with all systems with local interactions. An
      exact solution found for a large number of channels allows us to capture this
      physics and to predict transport properties.

PMID- 15245301
TI  - de Haas-van Alphen effect across the metamagnetic transition in Sr3Ru2O7.
AB  - We report a study of the de Haas-van Alphen (dHvA) effect on the itinerant
      metamagnet Sr3Ru2O7. Extremely high sample purity allows the observation of dHvA
      oscillations both above and below the metamagnetic transition field of 7.9 T. The
      quasiparticle masses are fairly large away from the transition, and are enhanced
      by up to an extra factor of 3 as the transition is approached, but the Fermi
      surface topography change is quite small. The results are qualitatively
      consistent with a field-induced Stoner transition in which the mass enhancement
      is the result of critical fluctuations.

PMID- 15245303
TI  - Detection of quantum confined states in au nanoclusters by alkali ion scattering.
AB  - Charge state-resolved time-of-flight spectra were collected for 2.0 keV 23Na+
      scattered from Au nanoclusters deposited on TiO2(110). The neutral fraction of Na
      scattered from metallic Au is low ( approximately 3%), but it is surprisingly
      high (up to 50%) for small clusters. The results demonstrate that alkali ions
      couple to electronic states specific to the nanoclusters, and that the energy of
      the states is a function of the nanocluster size. This technique provides a new
      method for the spectroscopy of nanomaterials.

PMID- 15245304
TI  - Variable range hopping conduction in semiconductor nanocrystal solids.
AB  - The temperature and electrical field dependent conductivity of n-type CdSe
      nanocrystal thin films is investigated. In the low electrical field regime, the
      conductivity follows sigma approximately exp([-(T(*)/T)(1/2)] in the temperature
      range 10<T<120 K. At high electrical field, the conductivity is strongly field
      dependent. At 4 K, the conductance increases by 8 orders of magnitude over one
      decade of bias. At a very high field, conductivity is temperature independent
      with sigma approximately exp([-(E(*)/E)(1/2)]. The complete behavior is very well
      described by variable range hopping with a Coulomb gap.

PMID- 15245305
TI  - Polarization surface-charge density of single semiconductor quantum rods.
AB  - Electrostatic force microscopy was used to determine that single CdSe quantum
      rods (QRs) have a permanent polarization surface-charge density, an unexpected
      observation for supposedly well-shaped particles. The surface charge results from
      a slight angle between the QR sides and the direction of internal electric
      polarization. By contrast, despite the large dipole moment expected for CdSe QRs,
      none was observed. The unavoidable presence of permanently charged surfaces on
      CdSe QRs has the potential to impede the development of novel devices
      incorporating these materials.

PMID- 15245306
TI  - Evidence for Luttinger-liquid behavior in crossed metallic single-wall nanotubes.
AB  - Transport measurements through crossed metallic single-wall nanotubes are
      presented. We observe a zero-bias anomaly in one tube which is suppressed by a
      current flowing through the other nanotube. These results are compared with a
      Luttinger-liquid model which takes into account electrostatic tube-tube coupling
      together with crossing-induced backscattering processes. Explicit solution of a
      simplified model is able to describe qualitatively the observed experimental data
      with only one adjustable parameter.

PMID- 15245307
TI  - Fast initial decay of molecular excitations at insulator surfaces.
AB  - We investigate the initial decay of electron-hole excitations in a molecular
      layer after adsorption on an insulator substrate surface. This is done within ab
      initio many-body perturbation theory by calculating the time propagation of
      excited two-particle states. For a CO monolayer adsorbed on the MgO(001) surface
      we find very fast decay processes with lifetimes that are about 5 times shorter
      than the transfer of single charge carriers. This is due to a strong coupling of
      the molecular excitations to charge-transfer-exciton states between the adlayer
      and the substrate.

PMID- 15245308
TI  - Spatial structure of an individual Mn acceptor in GaAs.
AB  - The wave function of a hole bound to an individual Mn acceptor in GaAs is
      spatially mapped by scanning tunneling microscopy at room temperature and an
      anisotropic, crosslike shape is observed. The spatial structure is compared with
      that from an envelope-function, effective mass model and from a tight-binding
      model. This demonstrates that anisotropy arising from the cubic symmetry of the
      GaAs crystal produces the crosslike shape for the hole wave function. Thus the
      coupling between Mn dopants in GaMnAs mediated by such holes will be highly
      anisotropic.

PMID- 15245309
TI  - Spontaneous supercurrent induced by ferromagnetic pi junctions.
AB  - We present magnetization measurements of mesoscopic superconducting niobium loops
      containing a ferromagnetic (PdNi) pi junction. The loops are prepared on top of
      the active area of a micro-Hall sensor based on high mobility GaAs/AlGaAs
      heterostructures. We observe asymmetric switching of the loop between different
      magnetization states when reversing the sweep direction of the magnetic field.
      This provides evidence for a spontaneous current induced by the intrinsic phase
      shift of the pi junction. In addition, the presence of the spontaneous current
      near zero applied field is directly revealed by an increase of the magnetic
      moment with decreasing temperature, which results in half integer flux
      quantization in the loop at low temperatures.

PMID- 15245310
TI  - Giant Nernst effect in CeCoIn5.
AB  - We present a study of Nernst and Seebeck coefficients of the heavy-fermion
      superconductor CeCoIn5. Below 18 K, concomitant with a field-dependent Seebeck
      coefficient, a large sublinear Nernst signal emerges with a magnitude drastically
      exceeding what is expected for a multiband Fermi-liquid metal. In the mixed
      state, in contrast with all other superconductors studied before, this signal
      overwhelms the one associated with the motion of superconducting vortices. The
      results point to a hitherto unknown source of transverse thermoelectricity in
      strongly interacting electrons.

PMID- 15245311
TI  - Systematic effects of carbon doping on the superconducting properties of Mg(B1
      xCx)(2).
AB  - The upper critical field, H(c2), of Mg(B1-xCx)(2) has been measured in order to
      probe the maximum magnetic field range for superconductivity that can be attained
      by C doping. Carbon doped MgB2 filaments were prepared, and for carbon levels
      below 4% the transition temperatures are depressed by about 1 K/% C and
      H(c2)(T=0) rises by about 5 T/% C. This means that 3.8% C substitution will
      depress T(c) from 39.2 to 36.2 K and raise H(c2)(T=0) from 16.0 to 32.5 T. These
      rises in H(c2) are accompanied by a rise in resistivity at 40 K from about 0.5 to
      about 10 microOmega cm.

PMID- 15245312
TI  - Direct relation between the low-energy spin excitations and superconductivity of
      overdoped high-Tc superconductors.
AB  - The dynamic spin susceptibility, chi(")(omega), has been measured over the energy
      range of 2</=omega</=10 meV for overdoped La2-xSrxCuO4. Incommensurate (IC) spin
      excitations are observed at 8 K for all superconducting samples for
      0.25</=x</=0.28 with chi(") peaking at approximately 6 meV. The IC peaks at 6 meV
      become smaller in intensity with increasing x and, finally, become unobservable
      for a sample with x=0.30 which has no bulk superconductivity. The maximum chi(")
      decreases linearly with T(c)(onset) in the overdoped region, implying a direct
      cooperative relation between the spin fluctuations and the superconductivity.

PMID- 15245313
TI  - Thermoinduced magnetization in nanoparticles of antiferromagnetic materials.
AB  - We show that there is a thermoinduced contribution to the magnetic moment of
      nanoparticles of antiferromagnetic materials. It arises from thermal excitations
      of the uniform spin-precession mode, and it has the unusual property that its
      magnitude increases with increasing temperature. This has the consequence that
      antiferromagnetism is nonexistent in nanoparticles at finite temperatures and it
      explains magnetic anomalies, which recently have been reported in a number of
      studies of nanoparticles of antiferromagnetic materials.

PMID- 15245314
TI  - Intrinsic susceptibility and bond defects in the novel two dimensional frustrated
      antiferromagnet Ba2Sn2ZnCr7pGa10-7pO22.
AB  - We present microscopic and macroscopic magnetic properties of the highly
      frustrated antiferromagnet Ba(2)Sn(2)ZnCr(7p)Ga(10-7p)O22, respectively, probed
      with NMR and SQUID experiments. The T variation of the intrinsic susceptibility
      of the Cr3+ frustrated Kagome bilayer, chi(Kag), displays a maximum around 45 K.
      The dilution of the magnetic lattice has been studied in detail for
      0.29</=p</=0.97. Novel dilution independent defects, likely related with magnetic
      bond disorder, are evidenced and discussed. We compare our results to
      SrCr(9p)Ga(12-9p)O19. Both bond defects and spin vacancies do not affect the
      average susceptibility of the Kagome bilayers.

PMID- 15245315
TI  - Self-healing of CdSe nanocrystals: first-principles calculations.
AB  - Ab initio calculations of the structural, electronic, and optical properties of
      CdSe nanoparticles are presented. The atomic structures of the clusters are
      relaxed both in vacuum and in the presence of surfactant ligands. In both cases,
      we predict significant geometrical rearrangements of the nanoparticle surface
      while the wurtzite core is maintained. These reconstructions lead to the opening
      of an optical gap without the aid of passivating ligands, thus "self-healing" the
      surface electronic structure. Our calculations also predict the existence of a
      midgap state responsible for recently observed subband emission.

PMID- 15245316
TI  - Nanodot-cavity electrodynamics and photon entanglement.
AB  - Quantum electrodynamics of excitons in a cavity is shown to be relevant to
      quantum operations. We present a theory of an integrable solid-state quantum
      controlled-phase gate for generating entanglement of two photons using a coupled
      nanodot-microcavity-fiber structure. A conditional phase shift of O(pi/10) is
      calculated to be the consequence of the giant optical nonlinearity keyed by the
      excitons in the cavities. Structural design and active control, such as
      electromagnetically induced transparency and pulse shaping, optimize the quantum
      efficiency of the gate operation.

PMID- 15245317
TI  - Light-induced gaps in semiconductor band-to-band transitions.
AB  - We observe a triplet around the third harmonic of the semiconductor band gap when
      exciting 50-100 nm thin GaAs films with 5 fs pulses at 3 x 10(12) W/cm(2). The
      comparison with solutions of the semiconductor Bloch equations allows us to
      interpret the observed peak structure as being due to a two-band Mollow triplet.
      This triplet in the optical spectrum is a result of light-induced gaps in the
      band structure, which arise from coherent band mixing. The theory is formulated
      for full tight-binding bands and uses no rotating-wave approximation.

PMID- 15245318
TI  - How to observe high-dimensional two-photon entanglement with only two detectors.
AB  - We propose a novel setup to investigate the entanglement of orbital angular
      momentum states living in a high-dimensional Hilbert space. We incorporate
      noninteger spiral phase plates in spatial analyzers, enabling us to use only two
      detectors. The two-photon states that are produced are not confined to a 2 x 2
      dimensional Hilbert space, and the setup allows the probing of correlations in a
      high-dimensional space. For the special case of half-integer spiral phase plates,
      we predict that the Clauser-Horne-Shimony-Holt-Bell parameter S is larger than
      achievable for two qubits (S=2 sqrt[2]), namely, S=31 / 5.

PMID- 15245319
TI  - Qubits versus bits for measuring an integral of a classical field.
AB  - Methods for measuring an integral of a classical field via local interaction of
      classical bits or local interaction of qubits passing through the field one at a
      time are analyzed. A quantum method, which has an exponentially better precision
      than any classical method we could see, is described.

PMID- 15245320
TI  - Entanglement as a precondition for secure quantum key distribution.
AB  - We demonstrate that a necessary precondition for an unconditionally secure
      quantum key distribution is that both sender and receiver can use the available
      measurement results to prove the presence of entanglement in a quantum state that
      is effectively distributed between them. One can thus systematically search for
      entanglement using the class of entanglement witness operators that can be
      constructed from the observed data. We apply such analysis to two well-known
      quantum key distribution protocols, namely, the 4-state protocol and the 6-state
      protocol. As a special case, we show that, for some asymmetric error patterns,
      the presence of entanglement can be proven even for error rates above 25% (4
      state protocol) and 33% (6-state protocol).

PMID- 15245321
TI  - Reconstruction of protein structures from a vectorial representation.
AB  - We show that the contact map of the native structure of globular proteins can be
      reconstructed starting from the sole knowledge of the contact map's principal
      eigenvector, and present an exact algorithm for this purpose. Our algorithm
      yields a unique contact map for all 221 globular structures of PDBselect25 of
      length N</=120. We also show that the reconstructed contact maps allow in turn
      for the accurate reconstruction of the three-dimensional structure. These results
      indicate that the reduced vectorial representation provided by the principal
      eigenvector of the contact map is equivalent to the protein structure itself.
      This representation is expected to provide a useful tool in bioinformatics
      algorithms for protein structure comparison and alignment, as well as a promising
      intermediate step towards protein structure prediction.

PMID- 15245322
TI  - Multichromophoric Forster resonance energy transfer.
AB  - The theory of Forster resonance energy transfer is generalized for
      multichromophoric (MC) and nonequilibrium situations. For the first time, it is
      clarified that the far-field linear spectroscopic information is insufficient for
      the determination of the reaction rate and that distance dependence of the rate
      can vary with the disorder and temperature. Application to a light harvesting
      complex LH2 reveals the important consequences of a MC structure.

PMID- 15245323
TI  - Universal behavior in a generalized model of contagion.
AB  - Models of contagion arise broadly in both the biological and the social sciences,
      with applications ranging from the transmission of infectious diseases to the
      spread of cultural fads. In this Letter, we introduce a general model of
      contagion which, by explicitly incorporating memory of past exposures to, for
      example, an infectious agent, rumor, or new product, includes the main features
      of existing contagion models and interpolates between them. We obtain exact
      solutions for a simple version of the model, finding that under general
      conditions only three classes of collective dynamics exist. Furthermore, we find
      that, for a given length of memory, the class into which a particular system
      falls is determined by only two parameters. Our model suggests novel measures for
      assessing the susceptibility of a population to large contagion events, and also
      a possible strategy for inhibiting or facilitating them.

PMID- 15245324
TI  - Scaling of directed dynamical small-world networks with random responses.
AB  - A dynamical model of small-world networks, with directed links which describe
      various correlations in social and natural phenomena, is presented. Random
      responses of sites to the input message are introduced to simulate real systems.
      The interplay of these ingredients results in the collective dynamical evolution
      of a spinlike variable S(t) of the whole network. The global average spreading
      length <L>(s) and average spreading time <T>(s) are found to scale as p(
      alpha)ln(N with different exponents. Meanwhile, S(t) behaves in a duple scaling
      form for N>>N(*): S approximately f(p(-beta)q(gamma)t), where p and q are
      rewiring and external parameters, alpha, beta, and gamma are scaling exponents,
      and f(t) is a universal function. Possible applications of the model are
      discussed.

PMID- 15245325
TI  - Organization of ecosystems in the vicinity of a novel phase transition.
AB  - It is shown that an ecosystem in equilibrium is generally organized in a state
      which is poised in the vicinity of a novel phase transition.

PMID- 15245326
TI  - Comment on "Electron correlation effects in resonant inelastic X-ray scattering
      of NaV2O5".

PMID- 15245328
TI  - Exchange model for oscillatory interlayer coupling and induced unidirectional
      anisotropy in [Pt/Co]3/NiO/[Pt/Co]3 multilayers.

PMID- 15245329
TI  - Anti-apoptotic protein Bcl-2 interacts with and destabilizes the
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA).
AB  - The anti-apoptotic effect of Bcl-2 is well established, but the detailed
      mechanisms are unknown. In the present study, we show in vitro a direct
      interaction of Bcl-2 with the rat skeletal muscle SERCA (sarcoplasmic/endoplasmic
      reticulum Ca2+-ATPase), leading to destabilization and inactivation of the
      protein. Recombinant human Bcl-2D21, a truncated form of Bcl-2 with a deletion of
      21 residues at the C-terminal membrane-anchoring region, was expressed and
      affinity-purified as a glutathione S-transferase fusion protein. Bcl-2D21 co
      immunoprecipitated and specifically interacted with SERCA in an in vitro-binding
      assay. The original level of Bcl-2 in sarcoplasmic reticulum vesicles was very
      low, i.e. hardly detectable by immunoblotting with specific antibodies. The
      addition of Bcl-2D21 to the sarcoplasmic reticulum resulted in the inhibition of
      the Ca2+-ATPase activity dependent on the Bcl-2D21/SERCA molar ratio and
      incubation time. A complete inactivation of SERCA was observed after 2.5 h of
      incubation at approx. 2:1 molar ratio of Bcl-2D21 to SERCA. In contrast, Bcl-2D21
      did not significantly change the activity of the plasma-membrane Ca2+-ATPase. The
      redox state of the single Cys158 residue in Bcl-2D21 and the presence of GSH did
      not affect SERCA inhibition. The interaction of Bcl-2D21 with SERCA resulted in a
      conformational transition of SERCA, assessed through a Bcl-2-dependent increase
      in SERCA thiols available for the labelling with a fluorescent reagent. This
      partial unfolding of SERCA did not lead to a higher sensitivity of SERCA towards
      oxidative inactivation. Our results suggest that the direct interaction of Bcl-2
      with SERCA may be involved in the regulation of apoptotic processes in vivo
      through modulation of cytoplasmic and/or endoplasmic reticulum calcium levels
      required for the execution of apoptosis.

PMID- 15245330
TI  - Comparative biochemical analysis of three bacterial prolyl endopeptidases:
      implications for coeliac sprue.
AB  - Prolyl endopeptidases have potential for treating coeliac sprue, a disease of the
      intestine caused by proteolytically resistant peptides from proline-rich
      prolamins of wheat, barley and rye. We compared the properties of three similar
      bacterial prolyl endopeptidases, including the known enzymes from Flavobacterium
      meningosepticum (FM) and Sphingomonas capsulate (SC) and a novel enzyme from
      Myxococcus xanthus (MX). These enzymes were interrogated with reference
      chromogenic substrates, as well as two related gluten peptides (PQPQLPYPQPQLP and
      LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), believed to play a key role in coeliac sprue
      pathogenesis. In vitro and in vivo studies were conducted to evaluate the
      activity, specificity and acid/protease stability of the enzymes. All peptidases
      were relatively resistant to acid, pancreatic proteases and membrane peptidases
      of the small intestinal mucosa. Although their activities against reference
      substrates were similar, the enzymes exhibited substantial differences with
      respect to chain length and subsite specificity. SC hydrolysed PQPQLPYPQPQLP
      well, but had negligible activity against LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF. In
      contrast, the FM and MX peptidases cleaved both substrates, although the FM
      enzyme acted more rapidly on LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF than MX. Whereas
      the FM enzyme showed a preference for Pro-Gln bonds, SC cleaved both Pro-Gln and
      Pro-Tyr bonds with comparable efficiency, and MX had a modest preference for Pro
      (Tyr/Phe) sites over Pro-Gln sites. While a more comprehensive understanding of
      sequence and chain-length specificity may be needed to assess the relative
      utility of alternative prolyl endopeptidases for treating coeliac sprue, our
      present work has illustrated the diverse nature of this class of enzymes from the
      standpoint of proteolysing complex substrates such as gluten.

PMID- 15245331
TI  - The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent
      transport of unconjugated bilirubin.
AB  - Results of previous studies have suggested that UCB (unconjugated bilirubin) may
      be transported by MRP1/Mrp1 (multidrug-resistance-associated protein 1). To test
      this hypothesis directly, [3H]UCB transport was assessed in plasma-membrane
      vesicles from MDCKII cells (Madin-Darby canine kidney II cells) stably
      transfected with human MRP1 or MRP2; wild-type MDCKII cells served as controls.
      As revealed by Western blotting, transfection achieved abundant expression of
      MRP1 and MRP2. [3H]UCB uptake was measured in the presence of 60 microM human
      serum albumin at a free (unbound) concentration of UCB (B(F)) ranging from 5 to
      72 nM and in the presence of 3 mM ATP or 3 mM AMP-PCP (adenosine 5'-[beta,gamma
      methylene]triphosphate). MRP1-transfected vesicles showed transport activity
      three and five times higher respectively compared with MRP2 or wild-type
      vesicles, whose transport did not differ significantly. [3H]UCB transport was
      stimulated 4-fold by 1.5 mM GSH, occurred into an osmotically sensitive space,
      was inhibited by 3 microM MK571 and followed saturative kinetics with K(m)=10+/-3
      nM (B(F)) and V(max)=100+/-13 pmol x min(-1) x (mg of protein)(-1). UCB
      significantly inhibited the transport of LTC4 (leukotriene C4), a leukotriene
      substrate known to have high affinity for MRP1. Collectively, these results prove
      directly that MRP1 mediates ATP-dependent cellular export of UCB and supports its
      role in protecting cells from bilirubin toxicity.

PMID- 15245333
TI  - Exercise testing.

PMID- 15245332
TI  - Basic residues play key roles in catalysis and NADP(+)-specificity in maize (Zea
      mays L.) photosynthetic NADP(+)-dependent malic enzyme.
AB  - C(4)-specific (photosynthetic) NADP(+)-dependent malic enzyme (NADP(+)-ME) has
      evolved from C(3)-malic enzymes and represents a unique and specialized form, as
      indicated by its particular kinetic and regulatory properties. In the present
      paper, we have characterized maize (Zea mays L.) photosynthetic NADP(+)-ME
      mutants in which conserved basic residues (lysine and arginine) were changed by
      site-directed mutagenesis. Kinetic characterization and oxaloacetate partition
      ratio of the NADP(+)-ME K255I (Lys-255-->Ile) mutant suggest that the mutated
      lysine residue is implicated in catalysis and substrate binding. Moreover, this
      residue could be acting as a base, accepting a proton in the malate oxidation
      step. At the same time, further characterization of the NADP(+)-ME R237L mutant
      indicates that Arg-237 is also a candidate for such role. These results suggest
      that both residues may play 'back-up' roles as proton acceptors. On the other
      hand, Lys-435 and/or Lys-436 are implicated in the coenzyme specificity (NADP(+)
      versus NAD(+)) of maize NADP(+)-ME by interacting with the 2'-phosphate group of
      the ribose ring. This is indicated by both the catalytic efficiency with NADP(+)
      or NAD(+), as well as by the reciprocal inhibition constants of the competitive
      inhibitors 2'-AMP and 5'-AMP, obtained when comparing the double mutant K435/6L
      (Lys-435/436-->Ile) with wild-type NADP(+)-ME. The results obtained in the
      present work indicate that the role of basic residues in maize photosynthetic
      NADP(+)-ME differs significantly with respect to its role in non-plant MEs, for
      which crystal structures have been resolved. Such differences are discussed on
      the basis of a predicted three-dimensional model of the enzyme.

PMID- 15245334
TI  - Microvolt T-wave alternans as predictor of electrophysiological testing results
      in professional competitive athletes.
AB  - BACKGROUND: Several studies have confirmed the equivalence of the microvolt T
      wave alternans (mTWA) and the electrophysiology (EPS) tests in cardiac disease.
      No data are available in populations of competitive athletes with arrhythmias
      that might jeopardize the pursuit of their professional career. METHODS: We
      prospectively studied 100 trained competitive athletes, including elite types
      (72/100), (mean age +/- standard deviation: 26.1 +/- 4.5 years). Forty-eight of
      them were wholly normal (Group A, mean age: 24.5 +/- 8.5 years) and 52 of them
      had severe arrhythmias (Group B, mean age: 28.2 +/- 11.5 years) and were
      symptomatic in 85% of cases for prolonged palpitations and syncope, but lacked
      any overt structural heart disease at standardized cardiological screening. All
      athletes were evaluated with the microvolt T-wave alternans exercise-stress test,
      using the Heart Wave System with Microvolt Sensors. Group B underwent EPS to
      evaluate inducibility to sustained ventricular tachycardia (VT) during programmed
      electrical stimulation. RESULTS: In Group A, the mTWA outcome was determinate in
      45 subjects (94%) and indeterminate in 3 (6%). No symptomatic event was reported
      in a follow-up of 36.1 months. In Group B, the mTWA test was positive in 7
      symptomatic subjects (15%), indeterminate in 3 (7%), and negative for the
      remaining 42 subjects (76%). Forty-one of 42 negative mTWA subjects were also
      negative in the EPS test, without any syncope or sustained VT during 25.3 months
      of follow-up. In the positive mTWA test subjects, 5 (72%) were positive for
      inducibility of rapid sustained monomorphic VT in EPS, 1 was positive for severe
      sustained atrial tachyarrhythmias, and 1 refused EPS. We were able to pronounce a
      correct diagnosis of lymphocytic myocarditis for only 1 mTWA and EPS-positive
      subject. For the other 4 positive patients with arrhythmogenic micropathology,
      severe arrhythmic events were revealed in the follow-up and aggressive hybrid
      treatment was necessary. CONCLUSION: Microvolt-TWA study seems to be a useful,
      noninvasive, and feasible tool for evaluating arrhythmic risk in the athletic
      population. The mTWA test showed a high negative predictive value, using both EPS
      and the follow-up observation for severe arrhythmic cardiac events as an
      endpoint. The positive predictive value was present in a limited number of cases
      that were, however, subjects with a high risk of sudden arrhythmic death.

PMID- 15245335
TI  - ST-depression with negative T waves in leads V4-V5--a marker of severe coronary
      artery disease in non-ST elevation acute coronary syndrome: a prospective study
      of Angina at rest, with troponin, clinical, electrocardiographic, and
      angiographic correlation.
AB  - BACKGROUND: The significance of ST-segment depression in acute coronary syndrome
      has been the subject of debate for many decades. Studies indicate that different
      manifestations of ST/T changes may have significantly different prognostic
      implications. METHODS AND RESULTS: We studied the correlation of ST/T changes in
      12-lead electrocardiography recorded during pain, to clinical and angiographic
      findings and in-hospital prognosis, in patients with non-ST-elevation acute
      coronary syndrome and elevated troponin levels. Fifty consecutive patients could
      be differentiated into two groups: (1) 25 patients with ST-segment depression and
      a negative T wave maximally in leads V4-5, (2) 25 patients with ST-segment
      depression and a positive T wave in the precordial lead with maximal ST-segment
      depression. Patients in group I had significantly more often left main or left
      main equivalent coronary artery disease; 76% versus 8% (P < 0.001), heart
      failure; 40% versus 4% (P = 0.005), and higher in-hospital mortality; 24% versus
      0% (P = 0.02), than patients in group II. The troponin levels did not differ
      significantly between the groups. CONCLUSIONS: In patients with non-ST-elevation
      acute coronary syndrome and elevated troponin levels two subgroups could be
      identified. Transient ST-segment depression and a negative T wave maximally in
      leads V4-5 during anginal pain predicts left main, left main equivalent, or
      severe three-vessel coronary artery disease with high sensitivity and
      specificity. In patients with ST-segment depression and a positive T wave, there
      is a high probability of one-vessel disease.

PMID- 15245336
TI  - Is baseline autonomic tone associated with new onset atrial fibrillation?:
      Insights from the framingham heart study.
AB  - BACKGROUND: Recent reports have indicated that autonomic tone fluctuations
      measured by heart rate variability (HRV) precede episodes of paroxysmal atrial
      fibrillation (AF). Little is known about the impact of baseline autonomic tone
      and the development of new onset AF in a population-based cohort. The purpose of
      this study was to assess the role of HRV as a predictor of new onset AF. METHOD:
      Ambulatory ECG recordings obtained from the Framingham Heart Study subjects
      attending a routine examination were processed for HRV. The HRV variables
      analyzed included standard deviation of normal R-R intervals (SDNN), low
      frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434
      women and 1142 men (54 +/- 14.1 years) eligible for the study. RESULTS: In 12
      years of follow-up, 65 women and 67 men had new onset AF. The study had 80% power
      to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in
      HRV. A one SD decrement in log LF/HF was associated with increased risk of
      developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06-1.44) in age- and
      sex-adjusted models; the association was no longer significant (HR = 1.15; 95% CI
      = 0.98-1.35) after adjusting for potential confounders. CONCLUSION: Autonomic
      dysregulation at baseline, as reflected by an altered HRV is associated with risk
      of AF; however, this association does not persist after adjusting for potential
      confounders. Much of the apparent association between HRV and AF is mediated by
      traditional risk factors.

PMID- 15245337
TI  - Detection of multivessel disease post myocardial infarction using an exercise
      induced QRS score.
AB  - OBJECTIVE: The aim of this study was to investigate the ability of Athens QRS
      score values to detect stenoses in other coronary arteries than the obstructed
      ones (which caused the myocardial infarction [MI]) in patients with a history of
      MI. METHODS: We studied 125 patients (93 males and 32 females, mean age 54 +/- 7
      years [range 45-68 years]) with a history of MI (46 patients with anterior MI, 54
      patients with inferior MI, 25 patients with lateral MI). All patients underwent
      treadmill exercise testing and coronary arteriography. RESULTS: Athens QRS score
      values were inversely related to the extent of CAD: -0.5 +/- 0.3 mm for patients
      with 1-VD (obstructed vessel), -3.4 +/- 2.2 mm for patients with 2-VD (obstructed
      vessel and stenosis in another vessel), and -5 +/- 1.8 mm for patients with 3-VD
      (obstructed vessel and stenoses in two more vessels). The ROC curves for the
      detection of multivessel disease showed that the area under the curve for QRS
      score values < -3 mm is significantly higher than the curve for ST-segment
      depression > or = 1 mm (0.948 vs 0.792, P < 0.001). CONCLUSIONS: Values of the
      Athens QRS score less than -3 may distinguish single- from multivessel coronary
      artery disease in patients with a history of MI.

PMID- 15245338
TI  - Sildenafil citrate does not alter ventricular repolarization properties: novel
      evidence from dynamic QT analysis.
AB  - BACKGROUND: Sildenafil citrate may have direct cardiac electrophysiological
      effects, and is possibly responsible for some cardiac events. The aim of our
      study was to investigate the effects of sildenafil citrate on QT dynamicity
      properties with a new QT analysis program showing even small changes in
      ventricular repolarization. METHODS: Twenty-four-hour Holter electrocardiographic
      recordings were used to obtain the data in the predrug phase (1-hour rest
      position before drug administration), and in the postdrug phase (1-hour rest
      position, which began 60 minutes after 50 mg oral sildenafil citrate
      administration). With the special QT analysis program (Verda, Reynolds Medical
      Ltd., UK); mean values of RR, QT, QTo (corrected QT), J (the exponent of
      correction formula) and S (QT/RR plots slope) parameters together with QT
      variability indexes (QTVI) were calculated for study phases. RESULTS: Mean +/-
      SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR:
      845 +/- 42 ms vs 816 +/- 46 ms, P < 0.05; QT: 371 +/- 8 ms vs 361 +/- 9 ms, P <
      0.05). However, sildenafil did not induce any significant change in mean +/- SEM
      values for QT(o), J, and S in postdrug phase compared with predrug phase (408 +/-
      10 ms vs 406 +/- 8 ms, 0.474 +/- 0.030 vs 0.433 +/- 0.025, 0221 +/- 0.020 vs
      0.198 +/- 0.017, respectively; P > 0.05). QTVIs were also not different in each
      phase (predrug: -0.874 +/- 0.071 vs postdrug: -0.997 +/- 0.067, P = 0.109).
      CONCLUSIONS: Fifty milligrams sildenafil does not affect QT dynamicity
      properties. The cardiac events associated with sildenafil could not be explained
      with ventricular arrhythmias.

PMID- 15245340
TI  - Decrease/disappearance of pacemaker stimulus "spikes" due to anasarca: further
      proof that the mechanism of attenuation of ECG voltage with anasarca is
      extracardiac in origin.
AB  - BACKGROUND: Recent work showed that AN leads to a decrement of the potentials of
      QRS complexes. Although the mechanism has been thought to be extracardiac in
      origin, and due to a decrease of the electrical impedance of the volume conductor
      from water overload, more proof on this will be welcome. It is hypothesized that
      the pacemaker "spikes" (PS) are independent of heart depolarization, and thus
      their change at the body surface with AN would be reflective of extracardiac
      influences. This study was designed to explore the impact of anasarca (AN) on the
      amplitude of PSs, and to further delineate the mechanism of ECG attenuation with
      AN. METHODS: The sum of PS measurements in millimeters in the 6 limb leads
      (SigmaPS6), and 12 ECG leads (SigmaPS12), and the sum of QRS complexes in the 6
      limb leads (SigmaQRS6), and 12 ECG leads (SigmaQRS12) were computed in six
      patients fitted with a pacemaker (3 with AN and 3 "controls"), and these
      variables were correlated with weight change. RESULTS: Correlation of percentage
      change in weight and SigmaPS12 was excellent (r = -0.88, P = 0.02), but not for
      SigmaPS6 (r = -0.73, P = 0.1). Also, the percentage weight correlated well with
      SigmaQRS6 (r = -0.82, P = 0.046), but not SigmaQRS12 (r = -0.61, P = 0.2).
      Correlation of percentage change in SigmaQRS6 and SigmaPS6 was excellent (r =
      0.91, P = 0.01), but not the percentage change in SigmaQRS12 and SigmaPS12 (r =
      0.72, P = 0.11). CONCLUSIONS: PSs undergo amplitude attenuation in patients
      developing AN, similar to the one noted in the QRS complexes. Since these changes
      are independent of the cardiac activation, and are similar in extent to those
      impacting the QRS complexes, the attenuation of the voltage of the entire ECG
      curve in AN appears to be extracardiac in origin.

PMID- 15245339
TI  - Temporal analysis of the depolarization wave of healed myocardial infarction in
      body surface potential mapping.
AB  - BACKGROUND: We studied the ability of different time segments of the
      depolarization wave recorded with body surface potential mapping (BSPM) to detect
      and localize myocardial infarction (MI). METHODS: BSPM was recorded in 24
      patients with remote MI and in 24 healthy controls. Cine and contrast-enhanced
      magnetic resonance imaging (MRI) was used as a reference method. Patients were
      grouped according to anatomical location of their MI. The QRS complex was divided
      into six temporally equal segments, for which time integrals were calculated.
      RESULTS: The time segments of the QRS complex showed different MI detection
      capability depending on MI location. For anterior infarction the second segment
      of the QRS complex was the best in MI detection and the optimal area was on the
      right inferior quadrant of the thorax (time integral average -1.5 +/- 1.8 mVms
      patients, 1.0 +/- 1.6 mVms controls, P = 0.002). For lateral infarction the first
      segment of the QRS complex performed best and the optimal area for MI detection
      was the left fourth intercostal area (time integral average 1.8 +/- 1.0 mVms
      patients, 0.7 +/- 0.5 mVms controls, P = 0.024). For inferior and posterior MI
      the mid-phases of the QRS complex were the best and the optimal area was the mid
      inferior area of the thorax (time integral average -6.2 +/- 8.3 mVms patients,
      3.3 +/- 4.3 mVms controls, P = 0.002; -9.1 +/- 6.1 mVms patients, 0.6 +/- 7.1
      mVms controls, P = 0.001, respectively). CONCLUSIONS: Time segment analysis of
      the depolarization wave offers potential for improving the detection and
      localization of healed MI.

PMID- 15245341
TI  - Patterns of QT dispersion in athletic and hypertensive left ventricular
      hypertrophy.
AB  - OBJECTIVE: The objective of this article is to assess whether left ventricular
      hypertrophy (LVH) due to physical training or of hypertensive patients shows
      similarities in QT length and QT dispersion. METHODS: A total of 51 subjects were
      studied: 17 essential hypertensive patients (27.7 +/- 5.6 years), 17 athletes
      involved in agonistic activity (canoeing) (24.8 +/- 6.1 years), and 17
      normotensive healthy subjects as control group (24.8 +/- 3.6 years). The testing
      protocol consisted of (1) clinic BP measurement, (2) echocardiography, (3) 12
      lead electrocardiographic examination (QT max, QTc max, QT min, QTc min, DeltaQT,
      DeltaQTc). RESULTS: There were no significant differences between the body
      surface area, height, and age of the three groups. Clinic blood pressure was
      higher in hypertensives (146.5 +/- 45.2/93.5 +/- 4.9 mmHg) versus athletes (120.9
      +/- 10.8/77.1 +/- 6.0 mmHg) and controls (123.5 +/- 4.8/78.8 +/- 2.9 mmHg) by
      definition. Indexed left ventricular mass (LVM/BSA) was significantly greater in
      both athletes (148.9 +/- 21.1 g/m2) and hypertensives (117.1 +/- 15.2 g/m2)
      versus controls (81.1 +/- 14.5 g/m2; P < 0.01), there being no statistical
      difference among them. LVH (LVMI > 125 g/m2) was observed in all athletes, while
      the prevalence in hypertensives was 50%. In spite of this large difference in
      cardiac structure there were no significant differences in QT parameters between
      athletes and the control group, while hypertensive patients showed a significant
      increase in QT dispersion versus the two other groups (DeltaQT 82 +/- 2.1, 48 +/-
      1.3, 49 +/- 2.3 ms; P < 0.01; DeltaQTc 88 +/- 2.0, 47 +/- 1.4, 54 +/- 2.7; P <
      0.01). CONCLUSIONS: LVH induced by physical training activity is not associated
      with an increase in QT dispersion, whereas pathological increase in LVM secondary
      to hypertension is accompanied by an increased QT dispersion.

PMID- 15245342
TI  - Abnormalities of the repolarization characteristics of patients with heart
      failure progress with symptom severity.
AB  - BACKGROUND: Congestive heart failure is a common condition with high mortality.
      Many of these deaths are sudden and unexpected. Ventricular action potential,
      surface repolarization (QT interval), and dispersion of repolarization are
      prolonged in the failing heart, contributing to arrhythmogenesis and sudden
      death. We studied the relationship between QT and heart rate (RR interval) from
      ambulatory recordings using a novel method in patients with ischemic heart
      disease and varying degrees of left-ventricular impairment (IHD) and compared
      them to healthy subjects (HS). We compare the degree of abnormality with the
      functional impairment and ejection fraction. METHODS: Using a previously
      described automated method for continuous estimation of the QT/RR characteristic
      that incorporates a correction formula for compensation of QT adaptation lag
      (VERDA, Del Mar Reynolds Medical Ltd., Hertford, UK), we compared recordings from
      41 IHD patients with age-matched HS. RESULTS: IHD Patients have prolonged 24-hour
      mean QTo (461 ms vs 426 ms, P < 0.01), and abnormal rate dependence relative to
      controls (24-hour mean slope: 0.20 vs 0.14, P < 0.001; J: 0.38 vs 0.28, P <
      0.001). There is increased temporal variation in J with respect to HS. These
      abnormalities of repolarization increase with worsening NYHA class, but do not
      correlate with ejection fraction. CONCLUSIONS: The use of a universal correction
      formula to compare dynamic QT data in IHD patients is inappropriate. The observed
      progressive abnormalities may be responsible for the high incidence of sudden
      death through promotion of arrhythmias.

PMID- 15245343
TI  - Enhanced external counterpulsation therapy: significant clinical improvement
      without electrophysiologic remodeling.
AB  - BACKGROUND: Enhanced external counterpulsation therapy (EECP), in addition to
      improving coronary flow and increasing the time to ischemia, noninvasively alters
      hemodynamics in patients with severe coronary artery disease (CAD). Other
      treatments that alter hemodynamics, for example, balloon valvuloplasty, left
      ventricular assist devices, and pharmacologic antagonism of the rennin
      angiotensin system, promote electrophysiologic remodeling, as evidenced by
      alterations in the QT interval. METHODS: We studied 28 patients who completed a 7
      week, 35-hour session of EECP to assess whether such therapy would also result in
      electrophysiologic remodeling. RESULTS: All patients had class II-III angina,
      imaging-proven ischemia, and severe, near-inoperable CAD. Of 28 patients, with a
      mean age 62 +/- 13 years (mean +/- SD), 78% were male, 46% diabetic, 82%
      hypertensive, 60% had undergone angioplasty, and 67% had undergone bypass
      surgery. The mean ejection fraction was 44% (range 25-60%). Following EECP, most
      patients (82%) had at least a one full class improvement in their anginal
      pattern. In most patients, there was substantial baseline conduction system
      disease present: a mean QRS of 105 +/- 19 ms. It is to be noted that there was no
      significant change in heart rate (HR), PR, QRS, or QT(c) intervals before and
      after EECP in either clinical responders or nonresponders. When analyzed by
      response to EECP, ejection fraction, or history of revascularization, there were
      still no detectable changes in ECG parameters (all P = NS). CONCLUSIONS: While
      EECP remains an effective treatment for severe CAD, it does not prompt early
      electrical remodeling of the heart.

PMID- 15245344
TI  - Risk stratification using heart rate turbulence and ventricular arrhythmia in
      MADIT II: usefulness and limitations of a 10-minute holter recording.
AB  - BACKGROUND: We evaluated the usefulness of heart rate turbulence (HRT) parameters
      and frequency of ventricular premature beats (VPBs) for risk-stratifying
      postinfarction patients with depressed left ventricular function enrolled in
      Multicenter Automatic Defibrillator Trial II (MADIT II). METHODS: In 884 MADIT II
      patients, 10-minute Holter monitoring at enrollment was used to evaluate HRT
      parameters and frequency of VPBs. The primary endpoints were defined as all-cause
      mortality in patients randomized to conventional treatment and as appropriate
      therapy for ventricular tachycardia or fibrillation in patients randomized to
      implantable cardioverter defibrillator (ICD) therapy. RESULTS: The median
      turbulence slope was lower in patients who died in comparison to survivors in the
      conventional arm (2.3 vs 4.5 ms/RR; P < 0.05); but it was not a significant
      predictor of mortality after adjustment for clinical covariates (age, ejection
      fraction, beta-blocker use, and BUN levels). There was no association between HRT
      parameters and arrhythmic events in ICD patients. Conventionally treated patients
      who died and ICD patients who had appropriate ICD therapy had significantly more
      frequent VPBs than those without such adverse events. After adjustment for
      clinical covariates, frequent VPBs>3/10 min were associated with death in the
      conventional arm (HR = 1.63; P = 0.070) and were predictive for appropriate ICD
      therapy in the ICD arm (HR = 1.75; P = 0.003). CONCLUSION: In postinfarction
      patients with severe left ventricular dysfunction, frequent VPBs are associated
      with increased risk of mortality and with appropriate ICD therapy. HRT obtained
      from 10-min Holter ECG showed a trend toward the association with mortality in
      univariate analysis but HRT parameters were not predictive of the outcome in
      multivariate analyses.

PMID- 15245345
TI  - Brugada and long QT-3 syndromes: two phenotypes of the sodium channel disease.
AB  - Brugada and long QT-3 syndromes are two allelic diseases caused by different
      mutations in SCN5A gene inherited by an autosomal dominant pattern with variable
      penetrance. Both of these syndromes are ion channel diseases of the heart
      manifest on surface electrocardiogram by ST-segment elevation in the right
      precordial leads and prolonged QT(c) interval, respectively, with predilection
      for polymorphic ventricular tachycardia and sudden death, which may be the first
      manifestation of the disease. Brugada syndrome usually manifests during adulthood
      with male preponderance, whereas long QT3 syndrome usually manifests in teenage
      years, although it can also manifest in adulthood. Class IA and IC antiarrhythmic
      drugs increase ST-segment elevation and predilection for polymorphic ventricular
      tachycardia and ventricular fibrillation in Brugada syndrome, whereas these
      agents shorten the repolarization and QT(c) interval, and thus may be beneficial
      in long QT-3 syndrome. Beta-blockade also increases the ST-segment elevation in
      Brugada syndrome but decreases the dispersion of repolarization in long QT-3
      syndrome. Mexiletine, a class IB sodium channel blocker decreases QT(c) interval
      as well as dispersion of repolarization in long QT-3 syndrome but has no effect
      on Brugada syndrome. The only effective treatment available at this time for
      Brugada syndrome is implantable cardioverter defibrillator, although repeated
      episodes of polymorphic ventricular tachycardia can be treated with
      isoproterenol. In symptomatic patients of long QT-3 syndrome in whom the torsade
      de pointes is bradycardia-dependent or pause-dependent, a pacemaker could be used
      to avoid bradycardia and pauses and an implantable cardioverter defibrillator is
      indicated where arrhythmia is not controlled with pacemaker and beta-blockade.
      However, the combination of new devices with pacemaker and cardioverter
      defibrillator capabilities appear promising in these patients warranting further
      study.

PMID- 15245346
TI  - Introductory note to a classic article by Robert A. Bruce.

PMID- 15245348
TI  - Beat-to-beat QT interval variability in atrial fibrillation with and without
      congestive cardiac failure.

PMID- 15245347
TI  - Exercising testing in adult normal subjects and cardiac patients. 1963.

PMID- 15245349
TI  - Allergy and eczema in context (and transition).

PMID- 15245350
TI  - The burden of atopy and asthma in children.
AB  - BACKGROUND: There has been a world-wide increase in the prevalence of atopic
      diseases. These atopic diseases, including asthma, allergic rhinoconjunctivitis
      and atopic eczema/dermatitis, are common in childhood and create a challenge of
      management for physicians and parents. METHODS: MEDLINE was searched for articles
      related to atopy, allergy asthma, allergic rhinoconjunctivitis and atopic
      eczema/dermatitis. RESULTS AND CONCLUSIONS: The conditions of asthma, allergic
      rhinoconjunctivitis and atopic eczema/dermatitis cause very significant burdens
      regarding the discomfort to the affected individual, management problems for the
      parent and physician and the economic cost to the family and the nation.

PMID- 15245351
TI  - A critical appraisal of 'evidence-based medicine' in allergy and asthma.
AB  - Clinical guidelines are 'systematically developed statements to assist
      practitioner and patient decisions about appropriate health care for specific
      clinical circumstances'. They may offer concise instructions on which diagnostic
      or screening tests to order, stipulate how medical services should be provided,
      how long patients should stay in hospital, or many other details relevant to
      clinical practice. This paper argues that guidelines should be simple, adapted to
      the clinical setting they inform and to treatment availability in their
      respective geographic context and that they should not be viewed as a yardstick
      but as support for physicians. The benefits of evidence-based-medicine (EBM),
      which defines the value of medical interventions in terms of empiric evidence
      from clinical trials, are growing in many contexts and are well described. Not
      sufficiently acknowledged, however, are the limits of EBM. A gap still exists
      between clinical research and clinical practice which should be better recognized
      and assessed.

PMID- 15245352
TI  - Characterization of bovine serum albumin epitopes and their role in allergic
      reactions.
AB  - OBJECTIVE: This review provides updated information on conformational and
      sequential epitopes identified in bovine serum albumin (BSA) and summarizes
      available data about the role of structural modifications on BSA
      antigenicity/allergenicity. DATA SOURCES: Data on beef allergy and BSA
      antigenicity are reported, with reference both to the basic literature and to
      clinical results obtained by our group. RESULTS AND DISCUSSION: BSA is an
      important allergen involved in milk and beef allergy. The presence of
      conformational epitopes has been suggested by indirect evidence, while at least
      one sequential epitope has been experimentally identified. The role of structural
      modifications on BSA antigenicity is discussed as well as the increased tolerance
      observed in allergic subjects consuming beef as strained (homogenized) and freeze
      dried derivatives. CONCLUSION: Study of the molecular characteristics of a known
      major allergen allows the identification of technological processes that may be
      capable of improving the tolerance of allergic subjects to a specific food. Even
      though any hoped for reduced allergenicity must be verified under medical
      supervision, the use of new products could obviate the need to avoid important
      foods such as meat in childhood.

PMID- 15245353
TI  - Immunoglobulin E- (IgE) and non-IgE-mediated reactions in the pathogenesis of
      atopic eczema/dermatitis syndrome (AEDS).
AB  - AEDS is a chronic, relapsing, highly pruritic inflammatory skin disease that
      commonly begins in childhood. Two forms of this disorder exist, i.e. an allergic
      (extrinsic) form and a nonallergic (intrinsic) form. There are clear genetic,
      humoral and cellular differences between the allergic and nonallergic forms of
      AEDS. The allergic variants express local IgE production in affected tissue and
      both allergic and nonallergic triggers play a major role in the expression of
      disease. The role of allergens is very important in the immunopathogenesis of
      AEDS. Nonimmunological triggers play a secondary modulatory role often hampering
      treatment effort and optimal response to therapeutic efforts.

PMID- 15245355
TI  - Role of oral food challenges in the diagnostic work-up of food allergy in atopic
      eczema dermatitis syndrome.
AB  - The diagnosis of food allergy in infants and children is still a challenging task
      for the pediatrician. While immediate-type allergic reactions to foods can be
      diagnosed quite easily, late-phase reactions, e.g. in atopic dermatitis, often
      represent a diagnostic challenge. Once classical diagnostic procedures such as
      history, skin prick tests, atopy patch test, and specific immunoglobulin E in
      serum have been exhausted, double-blind, placebo-controlled food challenges
      represent the state of the art. After an oligo-allergenic diet, suspected foods
      or placebo are given in a titrated manner until a clear clinical reaction or the
      highest dose. The observation period should be 48 h in the case of atopic
      dermatitis. Constant clinical monitoring is mandatory. Dietetic recommendations
      are given for 12 months. The effort involved in such a procedure is justified
      because it can help to avoid clinically relevant food allergens in some cases and
      in others can prevent children from being exposed unnecessarily to diets that may
      be harmful to them.

PMID- 15245354
TI  - Experience with quantitative IgE antibody analysis in relation to allergic
      disease within the BAMSE birth cohort--towards an improved diagnostic process.
AB  - This paper argues that with a certain allergen profile of airborne and food
      allergens and the use of total IgE-antibody levels, combined with the number of
      allergens positive at test represent a powerful tool to identify allergic disease
      in childhood. The allergens featured in such a profile will be dependent on the
      subject's age and geographical location.

PMID- 15245356
TI  - The utility of specific immunoglobulin E measurements in primary care.
AB  - BACKGROUND: The identification of atopic patients may not be considered a
      necessary step in the diagnosis process in primary care. This study investigated
      the impact of the addition of a specific immunoglobulin E (IgE) antibody test on
      the current management by primary-care physicians of patients with respiratory
      and skin symptoms. METHODS: The study had a prospective before-after design. It
      was conducted in two geographic areas of Italy and Spain and consisted of two
      parts, Part I and Part II. In each part patients were recruited according to
      inclusion and exclusion criteria. After the clinical examination, the patients
      were classified into one of the following categories using a physician's
      classification: allergic, nonallergic or uncertain. A blood sample was taken from
      each included patient for specific IgE antibody determination using a Pharmacia
      CAP System, including either Phadiatop Infant (0-5 years of age) or Phadiatop and
      food mix (fx5e) (>5 years of age). If a positive result was found, an additional
      6-26 specific IgE tests were performed. In Part I the result of the specific IgE
      antibody determinations was not available before the physician's classification
      was made. In contrast, in Part II, the result of the IgE test was available at
      the time when the physician's classification was made. Between Part I and Part II
      an educational intervention for physicians to improve their knowledge of blood
      testing for IgE-mediated allergy was carried out. RESULTS: A total of 721
      patients were included in the study. The agreement between classifications based
      on clinical data and IgE antibody results changed from a kappa coefficient of
      0.13 in Part I to 0.86 in Part II. With regard to the allergic status the
      proportion of uncertain cases was reduced from 26.3% in Part I to 4.1% in Part
      II. The proportion of patients that were advised to avoid allergens increased
      from 18% in Part I to 62% in Part II in the group of patients classified both by
      the clinician and the IgE test. CONCLUSIONS: The use of specific IgE antibody
      determinations improves the clinical management of patients with allergy related
      symptoms in primary care, allowing advice to be given on specific allergen
      avoidance. However, the applicability of this diagnostic tool in different areas
      and countries should be further assessed in cost-effectiveness studies.

PMID- 15245357
TI  - Breast-feeding and atopic eczema dermatitis syndrome: protective or harmful?
AB  - Numerous studies have addressed the potential of breast-feeding to protect for
      the development of allergic diseases, and in particular of atopic eczema
      dermatitis syndrome (AEDS). Although the majority of studies, as well as several
      meta-analyses, are strongly in favour of breast-feeding, there are some
      conflicting results and open issues. Furthermore, breast-feeding might be
      detrimental in a subgroup of young infants with severe early manifestations of
      AEDS and immunoglobulin E sensitizations to common foods. The aim of this review
      is not to analyse systematically the current literature, but to suggest a
      scientifically and clinically based analysis of the benefits of breast-feeding in
      atopic infants.

PMID- 15245358
TI  - Hypoallergenic formulas--when, to whom and how long: after more than 15 years we
      know the right indication!
AB  - Hypoallergenic formulas are processed by enzymatic hydrolysis of different
      protein sources such as bovine casein/whey and soy followed by further processing
      such as heat treatment and/or ultrafiltration, or they are based on amino acid
      mixtures. The products have been classified according to the degree of protein
      hydrolysis as 'extensively' or 'partially' hydrolysed protein products. Product
      properties may be characterized by biochemical techniques, and reduction of
      allergenicity may be assessed in vitro with various immunological methods, and in
      vivo with skin prick tests, patch tests and challenge tests. In vitro tests do
      not predict the allergenic effects in humans, and at present there is no evidence
      of a specific threshold of immunogenic protein. Only pure amino acid mixtures are
      considered to be nonallergenic. Other 'hypoallergenic' products contain residual
      allergenicity. At present, the potential of a product for treatment and
      prevention of food allergy can only be determined by clinical trials using
      scientifically appropriate standards. It has been recommended that dietary
      products for treatment of cow's milk protein allergy in infants should be
      tolerated by at least 90% (with 95% confidence) of infants with documented cow's
      milk protein allergy. Some extensively hydrolysed products and amino-acid-based
      products have met these criteria. Formulas intended for prevention should have a
      very low, if any, allergenic activity until otherwise proven. So far there are no
      firm criteria available for the design of hypoallergenic foods for prevention.
      Newborns included in prevention studies should be from high-risk families; they
      should be randomized at birth and fed the formula when supplements are needed for
      at least the first 4-6 months of life. Follow-up should be at least 18 months,
      and children should be investigated when symptoms appear. Validated clinical
      criteria, including controlled food challenges, should be used for diagnosis.
      Infants fed formulas that claim to prevent or delay allergy should have a
      statistically significant lower prevalence of allergy when compared with infants
      fed a standard cow's milk formula. Feeding high-risk infants a documented
      hypoallergenic formula combined with avoidance of solid foods during the first 4
      6 months reduces the cumulative incidence of cow's milk protein allergy and
      atopic dermatitis as compared with a standard cow's-milk-based formula. Partially
      hydrolysed formulas may have an effect, though it seems to be less than that of
      extensively hydrolysed formulas at present. Thus, if exclusive breast-feeding for
      4-6 months is not possible in high-risk infants, a documented hypoallergenic
      formula and avoidance of solid foods are recommended for the first 4 months of
      life.

PMID- 15245359
TI  - Environmental prevention in atopic eczema dermatitis syndrome (AEDS) and asthma:
      avoidance of indoor allergens.
AB  - Indoor allergens represent an important precipitating factor for both asthma and
      atopic eczema dermatitis syndromes (AEDS). There is also accumulating evidence
      that sensitization to those allergens is associated with the onset of atopic
      disorders. Patients with AEDS present aeroallergen-specific T-cell responses
      associated with worsening of symptoms when exposed to specific aeroallergens.
      Furthermore, application of indoor allergens to the skin of patient with AEDS
      induces a local eczematous response in one-third of these patients. Exposure to
      high concentrations of mite allergens in early infancy have been demonstrated to
      be a risk factor for developing atopic dermatitis during the first 3 years of
      life. Moreover, a clear dose-response relationship has been documented between
      mite exposure and disease activity. Primary prevention of AEDS by avoiding indoor
      allergen exposure has been proved to be effective only when allergenic foods have
      also been avoided. Mite allergen avoidance in infants with AEDS and food allergy
      may however, prevent mite sensitization and the onset of asthma. Indoor allergen
      avoidance has been demonstrated to be effective in the majority of studies
      performed in patients with established AEDS. Negative results may be explained
      either by individual susceptibility variation, by long duration of disease with
      the consequent irreversible pathological changes in the target tissue or by
      exposure to allergens outside the house. Education of the patients and public
      consciousness of the problems are crucial for the efficacy of indoor allergen
      avoidance in allergic diseases.

PMID- 15245360
TI  - The value of SCORAD and beyond. Towards a standardized evaluation of severity?
AB  - The clinical scoring systems of atopic dermatitis were analysed and compared.
      Some biological parameters that can correlate with the clinical score were also
      reviewed. After the definition of the disease based on validated clinical
      criteria, the second necessity was the availability of reliable severity scores
      to allow clinicians to verify the course of the disease and the efficacy of
      treatments. After many proposals, the SCORAD (SCORing Atopic Dermatitis), that
      required more than three years of work, was the first one that was validated.
      SCORAD is freely available from an internet site and can be easily calculated
      using dedicated software. EASI (Eczema Area and Severity Index) score has also
      been validated but it has been modified twice. Simpler systems include SASSAD
      (Six Area, Six Sign Atopic Dermatitis) and TIS score (Three-Item Severity score).
      In parallel, biological parameters were investigated. Eosinophil cationic
      protein, circulating basophils, major basic protein, soluble E-selectin,
      antistaphylococcal enterotoxin B, immunoglobulin E titres and macrophage-derived
      chemokine, can correlate significantly with the clinical score. The clinicians
      will not benefit directly from laboratory techniques and will employ clinical
      scores.

PMID- 15245361
TI  - Adverse food reactions by skin contact.
AB  - The skin is very much exposed to food contact, both in the occupational and
      nonoccupational settings. Through such an exposure, adverse reactions can occur
      that may be irritant or immunologic. Both such types of reactions are
      particularly common in children with atopic dermatitis. Immunologic reactions can
      be immediate (immunoglobulin E-mediated) or delayed (cell-mediated), and can be
      localized or systemic. The latter can be life-threatening, even following trivial
      exposure. Clinical and experimental data are accumulating to indicate that
      epicutaneous exposure to food can induce de novo systemic immunoglobulin E
      sensitization.

PMID- 15245362
TI  - Atopic keratoconjunctivitis.
AB  - Atopic keratoconjunctivitis (AKC) represents a disease usually classified under
      the term of allergic conjunctivitis together with seasonal allergic
      conjunctivitis (SAC), perennial allergic conjunctivitis (PAC) and vernal
      keratoconjunctivitis (VKC). However, AKC and VKC have clinical and
      pathophysiological features quite different from SAC and PAC, in spite of some
      common markers of allergy. This article aims to review personal studies
      suggesting that allergic conjunctivitis (similarly to asthma, rhinitis and atopic
      dermatitis) is a heterogeneous disease entity with different preferential
      pathogenetic mechanisms and a spectrum of clinical expression which varies
      according to individual cases. AKC and VKC may thus represent a model of atopy
      quite distinct from the classical type-1 hypersensitivity mechanism.

PMID- 15245363
TI  - Antihistamines: do they work? Further well-controlled trials involving larger
      samples are needed.
AB  - Histamine is one of the most important steps in the phlogistic allergic reaction.
      Its activity is due to the link to specific receptors on the cellular surface. H1
      receptors of second generation are the most currently prescribed drugs in
      allergic diseases for their high selectivity, little or no central sedative
      effect, rapid onset of action and long half lives. Antihistamines can modulate
      part of immunological mechanisms involved in the pathogenesis of allergic
      inflammation reducing mediator release and expression of adhesion molecules,
      regulating the release of cytokines, chemokines and consequently inflammatory
      cells recruitment. The anti-inflammatory effects of cetirizine, desloratadine and
      levocetirizine are reviewed. Quality of life is considered too, as a main
      parameter in a global evaluation of the antihistamine's effects.

PMID- 15245364
TI  - Dietary treatment of childhood atopic eczema/dermatitis syndrome (AEDS).
AB  - OBJECTIVE: This review summarizes the research and clinical evidence in favour of
      dietary intervention aimed at eliminating allergenic foods in the management of
      atopic eczema/dermatitis syndrome (AEDS). DATA SOURCES: The data source was
      PubMed, using a search algorithm selecting for clinical studies of AEDS, diet
      therapy and food allergy in all children to October 2003. Also included is a
      commentary based on the authors' clinical experience in the allergy unit of a
      university hospital in Italy. RESULTS: Fourteen prospective studies matched the
      entry criteria. Diverse trial designs, diagnostic criteria, types of dietary
      intervention and length of observation periods precluded meta-analytic methods.
      Allergenic food exclusion claimed efficacy in 13 of the 14 studies and was most
      useful in infants, in patients with elevated immunoglobulin E levels and/or
      multiple food sensitization and in patients with a diagnosis of food allergy.
      CONCLUSION: Dietary intervention in the form of an elimination diet is
      efficacious in children with AEDS when a specific diagnosis of food allergy has
      been made. Diagnostic evaluation of food allergy should be performed in all
      children with eczema, particularly in younger children and those with severe
      forms of the disease.

PMID- 15245365
TI  - Consensus guidelines in diagnosis and treatment of atopic dermatitis.
AB  - Atopic dermatitis is a common condition of great health significance. Consensus
      driven guidelines of care or specific practice parameters may be useful, as are
      treatment algorithms based upon disease severity. Development of consensus
      guidelines on diagnosis and treatment of atopic dermatitis are discussed, and
      disease-severity-based guidelines of care proposed.

PMID- 15245366
TI  - CD46: a complement regulator and pathogen receptor that mediates links between
      innate and acquired immune function.
AB  - In the last 10 years, the human cell-surface molecule, CD46, has evolved from
      'just another complement regulator' to a receptor for a striking array of
      pathogens. CD46 not only protects cells from complement-mediated attack and
      facilitates infection by a large number of pathogens, but also exerts complex
      effects on cellular immune function. It has been proposed that CD46 links innate
      and adaptive immunity by affecting cellular immune function in response to
      complement binding, and the role of CD46 in the pathogenesis of many infectious
      pathogens is now the subject of intense investigation. So far, the flood of
      information that implicates CD46 in modifying a host response to measles,
      Neisseria, human herpes virus 6, and pathogens that activate complement has not
      yet been matched with a comprehensive understanding of the molecular mechanisms
      by which CD46 affects immune function. This review summarizes the evidence that
      points to a significant role for CD46 in a range of pathological processes and
      describes how CD46 might exert its effects by altering signal transduction and
      antigen presentation pathways.

PMID- 15245367
TI  - Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized
      description of FCGR3B alleles.
AB  - The low-affinity Fc gamma receptor IIIb (Fc gamma RIIIb and CD16b) is constituted
      by a unique FCGR3B polypeptide chain that comprises two extracellular
      immunoglobulin-like domains, and is expressed as a glycosylphosphatidyl inositol
      anchored receptor on the neutrophils. The FCGR3B chain bears allotypes that
      define the human neutrophil antigen-1 (HNA-1 and NA) system involved in major
      post-transfusional reactions. FCGR3B is highly homologous to FCGR3A, which is
      expressed as a transmembrane receptor on natural killer cells and
      monocytes/macrophages. Its transcription products were not yet fully
      characterized. In the present work, we sequenced FCGR3B cDNAs with complete 3'
      untranslated region from purified granulocytes of HNA-1b/HNA-1b (NA2/NA2)
      genotyped donors. We characterized two FCGR3B cDNAs of different lengths
      corresponding to two polyadenylation sites. This result was corroborated by data
      raised by serial analysis of gene expression (SAGE). FCGR3B allele polymorphisms,
      from this article [FCGR3B*02 (HNA-1b, NA2)] and from the literature, are
      described for the first time according to the IMGT standardized nomenclature and
      to the IMGT unique numbering for C-LIKE-DOMAIN (http://imgt.cines.fr). These
      rules, described in the IMGT Scientific chart, are based on the IMGT-ONTOLOGY
      concepts. IMGT allele alignments and IMGT Collier de Perles graphical two
      dimensional representations are provided for the two Ig-like domains (or C-LIKE
      DOMAINs) [D1] and [D2] of FCGR3B*02. The standardized description of FCGR3B
      allele polymorphisms was approved by the IMGT Nomenclature Committee (IMGT-NC)
      and is freely available in IMGT repertoire at IMGT, http://imgt.cines.fr.

PMID- 15245368
TI  - Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules
      CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4).
AB  - The CD150 (SLAM) family consists of nine leukocyte cell-surface proteins involved
      in lymphocyte activation that belong to the immunoglobulin (Ig) superfamily. Six
      members of this family--CD84, CD150 (SLAM), CD229 (Ly9), CD244 (2B4), NTB-A, and
      CS1--associate with adapter proteins--SLAM-associated protein (SAP) and EAT-2.
      SAP is a short intracellular molecule that is mutated in humans with X-linked
      lymphoproliferative disease. Flow cytometric analysis of the expression of CD84,
      CD150, CD229, and CD244 cell-surface receptors on several leukocyte and
      lymphocyte subsets was performed. CD84 and CD150 were present on thymocytes,
      mature T cells and antigen-presenting cells. The expression of CD84 and CD150 was
      high on memory T cells. CD150 expression was strongly up-regulated after cell
      activation. In contrast to CD84, CD150 was absent on resting monocytes and
      immature dendritic cells (DCs). CD229 presented a pattern of expression
      restricted to lymphocytes. CD244 was preferentially expressed on natural killer
      cells, CD8(+) effector cells, resting monocytes, basophils, and eosinophils. We
      describe a broader distribution of CD84, CD150, CD229, and CD244 than previously
      reported and show that they are differentially expressed on hematopoietic cells.
      The heterogeneous expression of these receptors indicates that these molecules
      may play non-redundant functions in the regulation of both innate and adaptive
      immune responses.

PMID- 15245369
TI  - Molecular basis of predisposition to develop type 1 diabetes mellitus in North
      Indians.
AB  - Type 1 diabetes (T1D) mellitus is a multifactorial autoimmune disease where more
      than 90% of insulin-producing pancreatic beta cells are destroyed before the
      clinical manifestations, warranting a need to identify the children predisposed
      to get the disease. Of the 20 genomic intervals implicated for the risk to
      develop T1D, the major histocompatibility complex (MHC) region on chromosome
      6p21.31 (IDDM1) has been the major contributor, followed by 5' regulatory region
      of the insulin (INS) gene on chromosome 11p15.5 (IDDM2). MHC has a role in
      antigen presentation and IDDM2 has been shown to have a role in transcription of
      insulin in the thymus. Hence, alleles of human leukocyte antigen (HLA)-DRB1,
      DQB1, and insulin-linked variable number of tandem repeats (INS-VNTR) were
      studied in 110 T1D patients and 112 healthy controls using polymerase chain
      reaction and hybridization with sequence-specific oligonucleotide probes (PCR
      SSOP) and PCR restriction fragment length polymorphism (PCR-RFLP), respectively.
      HLA-DRB1*0301 was significantly increased in the T1D patients along with
      associated DQB1*0201 followed by DRB1*0401 and DRB1*0405. DRB1*0701 was observed
      to be the most protective allele followed by DRB1*0403 and DRB1*0404. Although
      DQB1*0302 which is associated with both the protective and susceptible DR4
      alleles was not significantly increased, heterozygous DQB1*0201, *0302 was
      significantly increased in the TID patients. Because INS-VNTR class I
      homozygosity was also significantly increased in the patients, simultaneous
      presence of DRB1*0301 along with homozygous INS-VNTR class I, gave a relative
      risk (RR) of 70.81. However, a similar analysis of DQB1*0201 and *0302 along with
      INS-VNTR alleles did not give such high RRs. Thus, the two independently
      assorting alleles at two loci i.e., DRB1*0301 and INS-VNTR class I, on two
      different chromosomes may have the potential to predict a prediabetic in North
      India.

PMID- 15245370
TI  - High-resolution DNA melting curve analysis to establish HLA genotypic identity.
AB  - High-resolution melting curve analysis is a closed-tube fluorescent technique
      that can be used for genotyping and heteroduplex detection after polymerase chain
      reaction. We applied this technique at the HLA-A locus and suggest that this
      method can be used as a rapid, inexpensive screen between siblings prior to
      living-related transplantation. At any locus, there are seven general cases of
      shared alleles among two individuals, ranging from identical homozygous genotypes
      (all alleles shared) to two heterozygous genotypes that share no alleles. We
      studied each case using previously typed cell lines to show that identity or non
      identity can be determined in all cases by high-resolution melting curve
      analysis. HLA genotype identity is suggested when two individuals have the same
      melting curves. Identity is confirmed by comparing the melting curve of a 1:1
      mixture with the individual melting curves. Non-identity at the amplified locus
      changes the heteroduplexes formed in the mixture compared with the original
      samples and alters the shape of the melting curve. The technique was tested on
      DNA from a 17-member CEPH family. High-resolution melting curve analysis revealed
      six different genotypes in the family. The genotype clustering was confirmed by
      sequence-based typing. Although this technique does not sequence or determine
      specific HLA alleles, it does rapidly establish identity at highly polymorphic
      HLA loci. The technique may also prove useful for confirmation of HLA genotypic
      identity between unrelated individuals prior to allogeneic hematopoietic stem
      cell transplantation.

PMID- 15245371
TI  - Comparative analysis of CD45 proteins in primate context: owl monkeys vs humans.
AB  - Transmembrane protein tyrosine phosphatase (PTPase) CD45 has been implicated in
      activating, differentiating and the development of different immune system cells.
      It regulates T-or B-cell activation during receptor-specific recognition by
      dephosphorylating tyrosine residues in protein kinase substrates. Aotus
      nancymaae, Aotus nigriceps, and Aotus vociferans CD45 nucleotide and deduced
      amino acid sequences are presented here, where we found 90-92% identity with the
      human counterpart in the nucleotide sequence and 83-86% in the amino acid
      sequence. Aotus CD45 alternative splicing isoforms include the same exons used in
      human CD45, producing several identical molecular weight nucleotide fragments.
      Most of the non-synonymous substitutions were found in the extracellular domain.
      The more conserved CD45 cytoplasmic portion has two intracellular phosphatase
      domains (D1 and D2) separated by a short spacer and some residues and motifs
      involved in signaling or molecular docking, intra- and intermolecular
      interactions and CD45 activity and activity regulation. All invariant residues
      and structural/functional motifs found in PTPases were totally conserved,
      suggesting that Aotus CD45 is a functional enzyme. Phylogenetic analysis has
      shown that the Aotus CD45 molecules are more related to the human homologs than
      to other reported vertebrate sequences and that the ancestral group of Aotus
      clade is A. vociferans. When Aotus species were compared, A. nigriceps and A.
      vociferans were the two most distant species, while A. nancymaae and A. nigriceps
      appeared to be a sister group. This could be relevant in deciding which Aotus
      species is to be used for studying particular immunological processes during
      lymphocyte activation or development.

PMID- 15245372
TI  - Polymorphisms of the equine major histocompatibility complex class II DRA locus.
AB  - The full extent of the polymorphism of ELA-DRA in Equidae is not yet known. Given
      the apparent differences in DRA polymorphisms between Equidae and other species,
      the aims of this study were to more fully characterize ELA-DRA, determine the
      extent of gene polymorphism and establish the allele-frequency distribution. An
      allele reference panel for the second exon of ELA-DRA was established by sequence
      based typing of 69 equine DNA samples consisting of various breeds of domestic
      horse (Equus caballus), together with donkeys (Equus asinus), Grant's zebras
      (Equus boehmi) and one onager (Equus hemionus). Five of the six previously
      reported alleles detected using single-strand conformation polymorphism were
      found: ELA-DRA*0101, ELA-DRA*0201, ELA-DRA*0301, ELA-DRA*0501 (Albright-Fraser DG
      et al. Polymorphism of DRA among equids. Immunogenetics 1996: 43: 315-7) and ELA
      DRA*0601 (GenBank accession number AF5419361). In addition to the previously
      reported alleles, five novel ELA-DRA alleles were detected within the ELA-DRA
      allele reference panel. One of these was identified in E. caballus (ELA
      DRA*JBH11), one in E. boehmi and E. hemionus (ELA-DRA*JBZ185) and three in E.
      asinus (ELA-DRA*JBD3, ELA-DRA*JBD17 and ELA-DRA*JBH45). A total of 565 equine DNA
      samples were screened using reference-strand-mediated conformation analysis, a
      double-stranded conformation-based mutation detection system that can be used to
      type existing ELA-DRA alleles and identify new variants. Based on our findings,
      at least 11 ELA-DRA alleles are now known to exist, and this level of
      polymorphism at the DRA locus appears to be unique to the genus Equus. Both the
      previously reported alleles and the new alleles displayed a species-specific
      distribution.

PMID- 15245373
TI  - Human leukocyte antigen-A, -B and -C alleles and human leukocyte antigen
      haplotypes in Turkey: relationship to other populations.
AB  - In this study, we present, for the first time, human leukocyte antigen (HLA)
      class I allele and haplotype frequencies at the DNA level in a sample of 142
      donors from Turkey. HLA typing was performed by medium-to-high resolution
      polymerase chain reaction sequence-specific oligonucleotide probes method. The
      most frequent HLA alleles at class I locus were A*0201(0.257), -B*35(0.204) and 
      Cw*04(0.173). A*0201-B*35-Cw*04(0.056) was the most common three-locus haplotype.
      Allele and haplotype frequency comparisons and neighbour-joining dendrograms,
      constructed using DA genetic distances and correspondence analysis using HLA-A, 
      B and -C, and -DRB1 allele frequencies, revealed similarities with other
      Mediterranean and European populations, but not with Mongol populations. These
      results agree with previous studies and confirm that the present day Turkish
      population is genetically more similar to its geographic neighbours than its
      historical neighbours in central Asia. The comprehensive HLA data on the Turkish
      population at the DNA level including up to six-locus putative haplotypes
      generated in this study will be useful for further studies.

PMID- 15245374
TI  - Investigation of killer cell immunoglobulin-like receptor gene diversity III.
      KIR2DL3.
AB  - The allelic variation of one of the chromosome 19 KIR genes, KIR2DL3, has been
      investigated using a polymerase chain reaction sequence-specific oligonucleotide
      probe-based methodology. The procedure has been applied to a healthy Northern
      Irish control group in order to establish phenotype and genotype frequencies in
      this Caucasian population. In addition, cell line DNA and Centre d'Etude du
      Humaine (CEPH) families, both from the 13th International Histocompatibility
      Workshop have been investigated, establishing control data for this gene.

PMID- 15245375
TI  - Haplotype variation at the IBD5/SLC22A4 locus (5q31) in coeliac disease in the
      Irish population.
AB  - In addition to the well-established association of coeliac disease (CD) with HLA
      DQ (6p21) and possibly CTLA4 (2q33), there is considerable evidence for a
      susceptibility locus on chromosome 5q, which contains many potential candidates
      for inflammatory disease, including a cluster of cytokine genes in 5q31. CD cases
      and controls were genotyped for four single-nucleotide polymorphism (SNP) markers
      that together characterize >90% of the haplotype variation at the IBD5 locus
      encoding, among others, the SLC22A4 gene. IBD5 and SLC22A4 map to 5q31 and have
      recently been associated with Crohn's disease and rheumatoid arthritis. Haplotype
      frequencies do not differ significantly between CD cases and controls in the
      Irish population, and therefore the chromosome 5 CD susceptibility locus most
      likely lies elsewhere on 5q.

PMID- 15245377
TI  - Polymorphism of HLA class I genes in the Brazilian population from the
      Northeastern State of Pernambuco corroborates anthropological evidence of its
      origin.
AB  - The allelic distribution of human leukocyte antigen (HLA) class I genes (HLA-A,
      HLA-B, and HLA-Cw) of the population from the State of Pernambuco in Northeastern
      Brazil was studied in a sample of 101 healthy unrelated individuals. Low to
      medium resolution HLA class I typing was performed using polymerase chain
      reaction-amplified DNA hybridized to sequence specific primers (PCR-SSPs). Twenty
      allele groups were detected for HLA-A, 28 for HLA-B, and 14 for HLA-Cw. The most
      frequent alleles were HLA-A*02(0.2871), HLA-B*15(0.1238), and HLA-Cw*04(0.2277),
      and the most frequent genotypes were A*02/A*02(0.0990), B*15/B*15(0.0594), and
      Cw*04/Cw*04 and Cw*07/Cw*07, both with a frequency of 0.0792. The observed
      heterozygosity for the studied loci was 79.21% for HLA-A, 87.13% for HLA-B, and
      77.23% for HLA-Cw. The most frequent haplotype was A*02-Cw*04-B*35(0.0485), which
      is also present in Western European, Amerindian, and Brazilian Mulatto
      populations, but absent in African populations. Taken together, these data
      corroborate the historic anthropological evidences of the origin of the
      Northeastern Brazilian population from Pernambuco.

PMID- 15245376
TI  - Lack of association between the -2518G/A polymorphism of the MCP-1 gene and
      ischaemic heart disease: a family-based investigation.
AB  - Using two recently described family-based tests of association, the possible role
      of the functional -2518G/A polymorphism in the promoter region of the monocyte
      chemoattractant protein-1 (MCP-1) gene in the susceptibility to ischaemic heart
      disease (IHD) was investigated in a well-defined Irish population. One thousand
      and twelve individuals from 386 families with at least one member prematurely
      affected with IHD were genotyped for the MCP-1 -2518G/A polymorphism. Using the
      combined transmission disequilibrium test and the pedigree disequilibrium test,
      no association between the MCP-1 -2518G/A polymorphism and IHD was found. Our
      data demonstrate that, in an Irish population, the MCP-1 -2518G/A polymorphism is
      not strongly associated with IHD.

PMID- 15245378
TI  - Identification of a new HLA-DRB1 allele in three members of an Italian family.
AB  - Abstract A new human leucocyte antigen (HLA)-DRB1 allele, HLA-DRB1*1149, has been
      identified in three members of an Italian family during routine sequence based
      typing. This new allele differs from HLA-DRB1*110101 only for a single nucleotide
      substitution at position 113 of exon 2 resulting in an amino acid change from
      Valine (GTG) to Alanine (GCG) at codon 38.

PMID- 15245379
TI  - A novel HLA-DRB1*13 allele (DRB1*1357) identified by polymerase chain reaction
      with sequence-specific primers and direct sequencing.
AB  - We describe the identification of a new DRB1*13 allele, DRB1*1357*, found in two
      Austrian Caucasian individuals. The novel allele was initially suspected because
      analysis with sequence-specific primers resulted in an unusual pattern of
      amplification. Thereafter, exon 2 was further characterized by sequence-based
      typing. The nucleotide sequence of DRB1*1357 is identical to DRB1*1319 except for
      a single substitution in codon 47 (TAC to TTC) leading to a change from
      phenylalanine to tyrosine.

PMID- 15245380
TI  - The cause of obesity: are we barking up the wrong tree?

PMID- 15245381
TI  - Childhood sexual abuse and obesity.
AB  - The causes of the current obesity epidemic are multifactorial and include
      genetic, environmental, and individual factors. One potential risk factor may be
      the experience of childhood sexual abuse. Childhood sexual abuse is remarkably
      common and is thought to affect up to one-third of women and one-eighth of men. A
      history of childhood sexual abuse is associated with numerous psychological
      sequelae including depression, anxiety, substance abuse, somatization, and eating
      disorders. Relatively few studies have examined the relationship between
      childhood sexual abuse and adult obesity. These studies suggest at least a modest
      relationship between the two. Potential explanations for the relationship have
      focused on the role of disordered eating, particularly binge eating, as well as
      the possible "adaptive function" of obesity in childhood sexual abuse survivors.
      Nevertheless, additional research on the relationship between childhood sexual
      abuse and obesity is clearly needed, not only to address the outstanding
      empirical issues but also to guide clinical care.

PMID- 15245382
TI  - Effects of obesity on women's reproduction and complications during pregnancy.
AB  - Obesity is increasing rapidly among women all over the world, and more women in
      fertile ages become overweight and obese. Among all other problems, women who are
      obese have higher rates of amenorrhoea and infertility. Obese women have a higher
      risk of complications during pregnancy such as hypertensive diagnoses and
      gestational diabetes, and delivery complications such as higher rates of
      caesarean sections and prolonged time of delivery. The aim of this article is to
      review the consequences of being obese during the reproductive life of a woman.

PMID- 15245383
TI  - Obesity as a disease: no lightweight matter.
AB  - The epidemic rise in obesity has fuelled the current debate over its
      classification as a disease. Contrary to just being a medical condition or risk
      factor for other diseases, obesity is a complex disease of multifaceted
      aetiology, with its own disabling capacities, pathophysiologies and
      comorbidities. It meets the medical definition of disease in that it is a
      physiological dysfunction of the human organism with environmental, genetic and
      endocrinological aetiologies. It is a response to environmental stimuli, genetic
      predisposition and abnormalities, and has a characteristic set of signs and
      symptoms with consistent anatomical alterations. Excess adipose tissue increases
      the work of the heart and leads to anatomical changes in this organ. It alters
      pulmonary, endocrine and immunological functions, all with adverse effects on
      health. Some of the complications of obesity include cardiovascular disease, non
      insulin-dependent diabetes mellitus, obstructive pulmonary disease, arthritis and
      cancer. Given the excess mortality, substantial morbidity and the economic toll
      of obesity, this is a disease that warrants serious attention by the medical
      community. Obesity's status and acceptance as a disease is pivotal in determining
      its treatment, reimbursement for treatment and the development of widespread
      interventions.

PMID- 15245384
TI  - Obesity, adipocytokines, and insulin resistance in breast cancer.
AB  - The adipocytokines are biologically active polypeptides that are produced either
      exclusively or substantially by the adipocytes, and act by endocrine, paracrine,
      and autocrine mechanisms. Most have been associated with obesity,
      hyperinsulinaemia, type 2 diabetes, and chronic vascular disease; in addition,
      six adipocytokines--vascular endothelial growth factor, hepatocyte growth factor,
      leptin, tumour necrosis factor-alpha, heparin-binding epidermal growth factor
      like growth factor, and interleukin-6--promote angiogenesis while one,
      adiponectin, is inhibitory. Obesity and insulin resistance have both been
      identified as risk factors for breast cancer and are associated with late-stage
      disease and poor prognosis. Angiogenesis is essential for breast cancer
      development and progression, and so it is plausible that obesity-related
      increases in adipocytokine production and a reduction in adiponectin may
      adversely affect breast cancer outcome by their angiogenesis-related activities.
      There is also experimental evidence that some adipocytokines can act directly on
      breast cancer cells to stimulate their proliferation and invasive capacity. Thus,
      adipocytokines may provide a biological mechanism by which obesity and insulin
      resistance are causally associated with breast cancer risk and poor prognosis.
      Both experimental and clinical studies are needed to develop this concept, and
      particularly in oestrogen-independent breast cancers where preventive and
      therapeutic options are limited.

PMID- 15245385
TI  - Psychiatric medication induced obesity: an aetiologic review.
AB  - A majority of psychiatric medications are known to generate weight gain and
      ultimately obesity in some patients. There is much speculation about the
      prevalence of weight gain and the degree of weight gain during acute and
      longitudinal treatment, but consensus shows that weight gain is prominent. The
      present review looked at the aetiology and cause of weight gain associated with
      psychotropic use and presents hypotheses as to why patients gain weight on
      antipsychotics, mood stabilizers and antidepressants. It is found that most
      psychotropic medications induce some weight gain, and clinicians are encouraged
      to utilize active interventions to alleviate the weight gain in order to prevent
      more serious obesity related comorbidities.

PMID- 15245386
TI  - Prevalence of obesity in Spain.
AB  - Obesity is a health problem affecting an important proportion of the Spanish
      population. Overweight is more common among men than women whereas, obesity is
      more prevalent among women. The most recent data (2001) from self-reported weight
      and height measurements of a Spanish representative sample (21120 subjects)
      revealed that the overall obesity prevalence in Spain was about 13%, while direct
      anthropometric data obtained from pooled surveys concerning eight Spanish regions
      (9885 subjects), which were carried out between 1990-2000 the obesity prevalence
      averaged 14.5%.

PMID- 15245388
TI  - Population structure of loggerhead shrikes in the California Channel Islands.
AB  - The loggerhead shrike (Lanius ludovicianus), a songbird that hunts like a small
      raptor, maintains breeding populations on seven of the eight California Channel
      Islands. One of the two subspecies, L. l. anthonyi, was described as having
      breeding populations on six of the islands while a second subspecies, L. l.
      mearnsi, was described as being endemic to San Clemente Island. Previous genetic
      studies have demonstrated that the San Clemente Island loggerhead shrike is well
      differentiated genetically from both L. l. anthonyi and mainland populations,
      despite the fact that birds from outside the population are regular visitors to
      the island. Those studies, however, did not include a comparison between San
      Clemente Island shrikes and the breeding population on Santa Catalina Island, the
      closest island to San Clemente. Here we use mitochondrial control region
      sequences and nuclear microsatellites to investigate the population structure of
      loggerhead shrikes in the Channel Islands. We confirm the genetic distinctiveness
      of the San Clemente Island loggerhead shrike and, using Bayesian clustering
      analysis, demonstrate the presence and infer the source of the nonbreeding
      visitors. Our results indicate that Channel Island loggerhead shrikes comprise
      three distinct genetic clusters that inhabit: (i) San Clemente Island, (ii) Santa
      Catalina Island and (iii) the Northern Channel Islands and nearby mainland; they
      do not support a recent suggestion that all Channel Island loggerhead shrikes
      should be managed as a single entity.

PMID- 15245387
TI  - Spatial genetic structure in two congeneric epiphytes with different dispersal
      strategies analysed by three different methods.
AB  - Three different approaches were used to assess the kinship structure of two
      epiphytic bryophytes, Orthotrichum speciosum and O. obtusifolium, that have
      different dispersal strategies. The two species were sampled in a 200 ha
      landscape where species occurrence and host trees had been mapped previously.
      Local environmental conditions at sampled trees were recorded and kinship between
      individuals was calculated based on amplified fragment length polymorphism (AFLP)
      marker data. We did not detect any association between AFLP-markers and
      investigated environmental conditions. In both species, significant kinship
      coefficients were found between individuals up to 300-350 m apart which shows
      that both species have a restricted dispersal range. The spatial kinship
      structure was detected with both autocorrelation analysis and generalized
      additive models (GAMs), but linear regression failed to detect any structure in
      O. speciosum. Although the dioecious O. obtusifolium is currently the more common
      species it may, none the less, due to its restricted dispersal range and
      reproduction mode, become threatened in the future by current silvicultural
      practices which enhance the distance between host trees and decrease their life
      span. Finally, GAMs seem most appropriate for analysing spatial genetic structure
      because the effects of local environmental conditions and spatial structure can
      be analysed simultaneously, no assumption of a parametric form between kinship
      coefficient and distance is required, and spatial data resolution is not lost in
      the arbitrary choice of distance classes characterizing autocorrelation analysis.

PMID- 15245389
TI  - Camouflaged invasion of Lake Malawi by an Oriental gastropod.
AB  - In this study we report the first animal invasion, to our knowledge, into Lake
      Malawi. The colonizer is a non-native morph of the gastropod Melanoides
      tuberculata that differs substantially in external shell characters from co
      occurring indigenous forms. However, because the species possesses extensive
      within-Africa geographical variation in shell morphology, it was unclear whether
      the invasion was range expansion of a native African morph, or a colonization
      from elsewhere. Mitochondrial DNA sequences indicate a southeast Asian origin for
      the invader, suggesting that shell variation found among indigenous allopatric
      populations camouflaged an intercontinental invasion.

PMID- 15245390
TI  - Strong genetic clines and geographical variation in gene flow in the rocky
      intertidal barnacle Balanus glandula.
AB  - A long-standing issue in marine biology is identifying spatial scales at which
      populations of sessile adults are connected by planktonic offspring. We examined
      the genetic continuity of the acorn barnacle Balanus glandula, an abundant member
      of rocky intertidal communities of the northeastern Pacific Ocean, and compared
      these genetic patterns to the nearshore oceanography described by trajectories of
      surface drifters. Consistent with its broad dispersal potential, barnacle
      populations are genetically similar at both mitochondrial (cytochrome oxidase I)
      and nuclear (elongation factor 1-alpha) loci across broad swaths of the species'
      range. In central California, however, there is a striking genetic cline across
      475 km of coastline between northern and southern populations. These patterns
      indicate that gene flow within central California is far more restricted
      spatially than among other populations. Possible reasons for the steep cline
      include the slow secondary introgression of historically separated populations, a
      balance between diversifying selection and dispersal, or some mix of both.
      Geographic trajectories of oceanic drifters closely parallel geographical
      patterns of gene flow. Drifters placed to the north (Oregon; approximately 44
      degrees N) and south (Santa Barbara, California; approximately 34 degrees N) of
      the cline disperse hundreds of kilometers within 40 days, yet over the long-term
      their trajectories never overlapped. The lack of communication between waters
      originating in Oregon and southern California probably helps to maintain strong
      genetic differentiation between these regions. More broadly, the geographical
      variation in gene flow implies that focusing on species-level averages of gene
      flow can mask biologically important variance within species which reflects local
      environmental conditions and historical events.

PMID- 15245391
TI  - Natural selection of the major histocompatibility complex (Mhc) in Hawaiian
      honeycreepers (Drepanidinae).
AB  - The native Hawaiian honeycreepers represent a classic example of adaptive
      radiation and speciation, but currently face one the highest extinction rates in
      the world. Although multiple factors have likely influenced the fate of Hawaiian
      birds, the relatively recent introduction of avian malaria is thought to be a
      major factor limiting honeycreeper distribution and abundance. We have initiated
      genetic analyses of class II beta chain Mhc genes in four species of
      honeycreepers using methods that eliminate the possibility of sequencing mosaic
      variants formed by cloning heteroduplexed polymerase chain reaction products.
      Phylogenetic analyses group the honeycreeper Mhc sequences into two distinct
      clusters. Variation within one cluster is high, with dN > dS and levels of
      diversity similar to other studies of Mhc (B system) genes in birds. The second
      cluster is nearly invariant and includes sequences from honeycreepers
      (Fringillidae), a sparrow (Emberizidae) and a blackbird (Emberizidae). This
      highly conserved cluster appears reminiscent of the independently segregating Rfp
      Y system of genes defined in chickens. The notion that balancing selection
      operates at the Mhc in the honeycreepers is supported by transpecies polymorphism
      and strikingly high dN/dS ratios at codons putatively involved in peptide
      interaction. Mitochondrial DNA control region sequences were invariant in the
      i'iwi, but were highly variable in the 'amakihi. By contrast, levels of
      variability of class II beta chain Mhc sequence codons that are hypothesized to
      be directly involved in peptide interactions appear comparable between i'iwi and
      'amakihi. In the i'iwi, natural selection may have maintained variation within
      the Mhc, even in the face of what appears to a genetic bottleneck.

PMID- 15245392
TI  - Living with uncertainty: genetic imprints of climate shifts in East Pacific
      anchovy (Engraulis mordax) and sardine (Sardinops sagax).
AB  - In the upwelling zone of the northeastern Pacific, cold nutrient-rich conditions
      alternate with warm nutrient-poor intervals on timescales ranging from months to
      millennia. In this setting, the abundances of Pacific sardine (Sardinops sagax)
      and northern anchovy (Engraulis mordax) fluctuate by several orders of magnitude,
      with sardine dominating during warm conditions and anchovy dominating during cool
      conditions. Two population models can explain the response of these fishes to
      adverse conditions. Under the basin model, species distributions contract to a
      central (optimal) range during population crashes. Expectations of this model may
      include a single range-wide population with a decline in genetic diversity on
      both sides of a central refuge. In contrast, the self-recruitment model invokes a
      series of local oceanographic domains that maintain semi-isolated subpopulations.
      During adverse conditions, some subpopulations cannot complete the life cycle
      within the local environment and are extirpated. Expectations of this model
      include some degree of population genetic structure and no clear gradient in
      genetic diversity. We examined mitochondrial DNA cytochrome b sequences to assess
      these competing models for anchovy (N = 196; 539 bp) and sardine (N = 107; 425
      bp). The mitochondrial DNA gene genealogies are shallow but diverse for both
      species. Haplotype frequencies are homogeneous among subpopulations, but genetic
      diversities peak for both species along Baja California and adjacent southern
      California. Mismatch distributions and Tajima's D-values reveal distinctive
      signatures of population bottlenecks and expansions. Sardine haplotypes coalesce
      at approximately 241,000 years bp, with an initial female effective population
      size Nf0 = 0 followed by exponential growth to Nf1 = 115 million. Anchovy
      haplotypes coalesce at approximately 282,000 years bp, with an initial population
      size of Nf0 = 14,000, followed by exponential growth to Nf1 = 2.3 million. These
      results indicate a founder event for sardine and a severe population decline for
      anchovy in the California Current during the late Pleistocene. Overall, these
      data support the basin model on decadal timescales, although local recruitment
      may dominate on shorter timescales.

PMID- 15245393
TI  - Effects of hydrographic barriers on population genetic structure of the sea star
      Coscinasterias muricata (Echinodermata, Asteroidea) in the New Zealand fiords.
AB  - New Zealand's 14 deep-water fiords possess persistent salinity stratification and
      mean estuarine circulation that may serve to isolate populations of marine
      organisms that have a dispersal larval phase. In order to investigate this idea,
      we analysed the population structure of the sea star Coscinasterias muricata
      using a mitochondrial DNA marker. Genetic differentiation among populations of C.
      muricata was analysed using 366 base pairs of mtDNA D-loop. We compared
      populations from the fiords with several others sampled from around New Zealand.
      At a macro-geographical scale (> 1000 km), restricted gene flow between the North
      and South Islands was observed. At a meso-geographical scale (10-200 km),
      significant population structure was found among fiords and between fiords and
      open coast. The pattern of population genetic structure among the fiords suggests
      a secondary contact between a northern population and a southern one, separated
      by a contact or mixing zone. These populations may have diverged by the effects
      of random genetic drift and population isolation as a consequence of the
      influence of estuarine circulation on dispersal. In northern Fiordland, genetic
      structure approximated an isolation by distance model. However, the pattern in
      genetic differences suggests that distance alone cannot explain the most
      divergent populations and that fiord hydrography may increase the effect of
      genetic drift within populations in the fiords. Finally, our study indicates that
      populations within the fiords underwent recent rapid expansion, followed most
      probably by genetic drift due to a lack of gene flow among the fiords.

PMID- 15245394
TI  - Genetic diversity and population structure of Tasmanian devils, the largest
      marsupial carnivore.
AB  - Genetic diversity and population structure were investigated across the core
      range of Tasmanian devils (Sarcophilus laniarius; Dasyuridae), a wide-ranging
      marsupial carnivore restricted to the island of Tasmania. Heterozygosity (0.386
      0.467) and allelic diversity (2.7-3.3) were low in all subpopulations and allelic
      size ranges were small and almost continuous, consistent with a founder effect.
      Island effects and repeated periods of low population density may also have
      contributed to the low variation. Within continuous habitat, gene flow appears
      extensive up to 50 km (high assignment rates to source or close neighbour
      populations; nonsignificant values of pairwise FST), in agreement with movement
      data. At larger scales (150-250 km), gene flow is reduced (significant pairwise
      FST) but there is no evidence for isolation by distance. The most substantial
      genetic structuring was observed for comparisons spanning unsuitable habitat,
      implying limited dispersal of devils between the well-connected, eastern
      populations and a smaller northwestern population. The genetic distinctiveness of
      the northwestern population was reflected in all analyses: unique alleles;
      multivariate analyses of gene frequency (multidimensional scaling, minimum
      spanning tree, nearest neighbour); high self-assignment (95%); two distinct
      populations for Tasmania were detected in isolation by distance and in Bayesian
      model-based clustering analyses. Marsupial carnivores appear to have stronger
      population subdivisions than their placental counterparts.

PMID- 15245395
TI  - Microsatellite variation reveals high levels of genetic variability and
      population structure in the gorgonian coral Pseudopterogorgia elisabethae across
      the Bahamas.
AB  - The primary mechanism of gene flow in marine sessile invertebrates is larval
      dispersal. In Pseudopterogorgia elisabethae, a commercially important Caribbean
      gorgonian coral, a proportion of the larvae drop to the substratum within close
      proximity to the maternal colony, and most matings occur between individuals in
      close proximity to each other. Such limited dispersal of reproductive propagules
      suggests that gene flow is limited in this gorgonian. In this study, we
      characterized the population genetic structure of P. elisabethae across the
      Bahamas using six microsatellite loci. P. elisabethae was collected from 18 sites
      across the Bahamas. Significant deviations from Hardy-Weinberg equilibrium due to
      deficits of heterozygotes within populations were detected for all 18 populations
      in at least one of the six screened loci. Levels of genetic structure among
      populations of P. elisabethae were high and significant. A distance analysis
      placed populations within three groups, one formed by populations located within
      Exuma Sound, a semi-isolated basin, another consisting of populations located
      outside the basin and a third group comprising two populations from San Salvador
      Island. The patterns of genetic variation found in this study are concordant with
      the life-history traits of the species and in part with the geography of the
      Bahamas. Conservation and management plans developed for P. elisabethae should
      considered the high degree of genetic structure observed among populations of the
      species, as well as the high genetic diversity found in the San Salvador and the
      Exuma Sound populations.

PMID- 15245396
TI  - Rapid recovery of genetic diversity of dogwhelk (Nucella lapillus L.) populations
      after local extinction and recolonization contradicts predictions from life
      history characteristics.
AB  - The dogwhelk Nucella lapillus is a predatory marine gastropod populating North
      Atlantic rocky shores. As with many other gastropod species, N. lapillus was
      affected by tributyltin (TBT) pollution during the 1970s and 1980s, when local
      populations became extinct. After a partial ban on TBT in the United Kingdom in
      1987, vacant sites have been recolonized. N. lapillus lacks a planktonic larval
      stage and is therefore expected to have limited dispersal ability. Relatively
      fast recolonization of some sites, however, contradicts this assumption. We
      compared levels of genetic diversity and genetic structuring between recolonized
      sites and sites that showed continuous population at three localities across the
      British Isles. No significant genetic effects of extinction/recolonization events
      were observed in SW Scotland and NE England. In SW England we observed a decrease
      in genetic diversity and an increase in genetic structure in recolonized
      populations. This last result could be an artefact, however, due to the
      superposition of other local factors influencing the genetic structuring of
      dogwhelk populations. We conclude that recolonization of vacant sites was
      accomplished by a relatively high number of individuals originating from several
      source populations (the 'migrant-pool' model of recolonization), implying that
      movements are more widespread than expected on the basis of development mode
      alone. Comparison with published data on genetic structure of marine organisms
      with contrasted larval dispersal supports this hypothesis. Our results also
      stress the importance of local factors (geographical or ecological) in
      determining genetic structure of dogwhelk populations.

PMID- 15245397
TI  - The diminutive supercolony: the Argentine ants of the southeastern United States.
AB  - Native to Argentina and Brazil, the Argentine ant (Linepithema humile) is an
      invasive species that has become established on six continents and many oceanic
      islands. In several parts of its introduced range, including the western United
      States, southern Europe and Chile, the Argentine ant is unicolonial, forming
      extensive supercolonies. We examined population genetic structure and intercolony
      aggression in two regions of the introduced range of this species in the United
      States: California and the southeastern United States. Our results show that the
      southeastern L. humile population has high genotypic variability and strong
      intercolony aggression relative to the California population. In the California
      population, intercolony aggression was absent and 23 alleles were found across
      seven polymorphic microsatellite loci. However, in the Southeast, aggression
      between colonies was high and 47 alleles were present across the same seven loci
      in an equal number of colonies. We suggest that distinctly different colonization
      patterns for California and the Southeast may be responsible for the striking
      disparity in the genetic diversity of introduced populations. Southeastern
      colonies may have descended from multiple, independent introductions from the
      native range, undergoing a bottleneck at each introduction. In contrast, the
      California supercolony may have originated from one or more colonies inhabiting
      the southeastern United States, thus experiencing a double bottleneck. The
      differences in present-day distribution patterns between California and the
      Southeast may be due to the combined effect of two factors: lower winter
      temperatures in the Southeast and/or competition with another successful and
      widely distributed ant invader, the fire ant Solenopsis invicta.

PMID- 15245398
TI  - Population genetics after fragmentation: the case of the endangered Spanish
      imperial eagle (Aquila adalberti).
AB  - The highly endangered Spanish imperial eagle, Aquila adalberti, has suffered from
      both population decline and fragmentation during the last century. Here we
      describe the current genetic status of the population using an extensive sampling
      of its current distribution range and both mitochondrial control region sequences
      and nuclear microsatellite markers. Results were evaluated in comparison to those
      obtained for the Eastern imperial eagle, Aquila heliaca, its nearest extant
      relative. Mitochondrial haplotype diversity was lower in the Spanish than in the
      Eastern species whereas microsatellite allelic richness and expected
      heterozygosity did not differ. Both allelic richness and expected heterozygosity
      were lower in the small Parque Nacional de Donana breeding nucleus compared to
      the remaining nuclei. A signal for a recent genetic bottleneck was not detected
      in the current Spanish imperial eagle population. We obtained low but significant
      pairwise FST values that were congruent with a model of isolation by distance.
      FST and exact tests showed differentiation among the peripheral and small Parque
      Nacional de Donana population and the remaining breeding subgroups. The centrally
      located Montes de Toledo population did not differ from the surrounding Centro,
      Extremadura and Sierra Morena populations whereas the latter were significantly
      differentiated. On the other hand, a Bayesian approach identified two groups,
      Parque Nacional de Donana and the rest of breeding nuclei. Recent migration rates
      into and from Parque Nacional de Donana and the rest of breeding nuclei were
      detected by assignment methods and estimated as 2.4 and 5.7 individuals per
      generation, respectively, by a Bayesian approach. We discuss how management
      strategies should aim at the maintenance of current genetic variability levels
      and the avoidance of inbreeding depression through the connection of the
      different nuclei.

PMID- 15245399
TI  - Phylogeographical structure, distribution and genetic variation of the green
      algae Ulva intestinalis and U. compressa (Chlorophyta) in the Baltic Sea area.
AB  - The marine algae Ulva intestinalis and U. compressa are morphologically plastic
      with many overlapping characters and are therefore difficult to distinguish from
      each other. The present distribution of U. intestinalis and U. compressa is
      investigated along the salinity gradient in the Baltic Sea area through analyses
      of internal transcribed spacer (ITS) sequence data. Also, the amount and
      distribution of intraspecific genetic polymorphism in the ITS region is studied
      allowing inferences on the phylogeographical pattern and postglacial
      recolonization of the Baltic Sea area. The data show that of the two species only
      U. intestinalis occurs in the Baltic Sea. The distribution of U. compressa is
      more restricted than previously reported, and it was not found in salinities
      lower than 15 ppt. All of Scandinavia and the Baltic Sea were covered with ice
      during the last ice age and the organisms in the Baltic Sea must have colonized
      the area after the ice had started to melt. The genetic diversity of U.
      intestinalis and U. compressa in the Baltic Sea and the neighbouring area was
      found to be reduced compared to that in the British Isles. This reduction may be
      the result of either a historical reduction of diversity or an adaptation of
      specific clones to the northern environmental conditions.

PMID- 15245400
TI  - Natural hybridization between Senecio jacobaea and Senecio aquaticus: molecular
      and chemical evidence.
AB  - Hybridization is known to be involved in a number of evolutionary processes,
      including species formation, and the generation of novel defence characteristics
      in plants. The genus Senecio of the Asteraceae family is highly speciose and has
      historically demonstrated significant levels of interspecific hybridization. The
      evolution of novel chemical defence characteristics may have contributed to the
      success of Senecio hybrids. Chemical defence against pathogens and herbivores has
      been studied extensively in the model species Senecio jacobaea, which is thought
      to hybridize in nature with Senecio aquaticus. Here, we use amplified fragment
      length polymorphisms (AFLPs) and pyrrolizidine alkaloid (PA) composition to
      confirm that natural hybridization occurs between S. jacobaea and the closely
      related species S. aquaticus. AFLPs are also used to estimate the ancestry of
      hybrids. We also demonstrate that even highly back-crossed hybrids can possess a
      unique mixture of defence chemicals specific to each of the parental species.
      This hybrid system may therefore prove to be useful in further studies of the
      role of hybridization in the evolution of plant defence and resistance.

PMID- 15245401
TI  - The effect of the last glacial age on speciation and population genetic structure
      of the endangered Ethiopian wolf (Canis simensis).
AB  - During the last glacial age, Afro-alpine habitats were widespread across the
      highlands of Ethiopia. A wolf-like canid ancestor is thought to have colonized
      this expanding habitat and given rise to a new species that was remarkably well
      adapted to the high altitude environment: the Ethiopian wolf Canis simensis.
      Here, we address the timing of genetic divergence and examine population genetic
      history and structure by investigating the distribution of mitochondrial DNA
      (mtDNA) sequence variation. The pattern of mtDNA variation and geographical
      distribution indicate an initial population expansion, probably immediately after
      divergence from the wolf-like ancestor, around 100,000 years ago. The partition
      of mtDNA haplotypes that followed was most likely the result of habitat reduction
      and fragmentation at the onset of deglaciation approximately 15,000 years ago.
      Phylogenetic and geographical associations suggest that the most likely genetic
      partitioning corresponds to three mountain areas, Arsi/Bale, Wollo/Shoa and
      Simien/Mt. Guna. Although there is a degree of clustering of haplotypes from both
      sides of the Rift Valley, the lack of reciprocal monophyly does not support the
      taxonomic classification of two subspecies. This study highlights the importance
      of populations north of the Rift Valley for the maintenance of genetic
      variability within the species and has consequent implications for conservation.

PMID- 15245402
TI  - Geographic genetic architecture of pocket gopher (Thomomys bottae) populations in
      Baja California, Mexico.
AB  - Phylogenetic analyses of complete mitochondrial cytochrome b sequences support
      the monophyly of pocket gopher (Thomomys bottae) populations from the 1000 km
      length of the Baja California peninsula of Mexico, relative to other geographical
      segments of the species range in western North America. The Baja California
      peninsula is an area that encompasses considerable ecomorphological and
      infraspecific diversity within this pocket gopher species. However, detailed
      population analyses encompassing 35 localities distributed over the southern half
      of the peninsula reveal only trivial phylogeographical structure. Rather, most of
      the 72 unique 500-base pair haplotypes examined from 142 individuals is
      restricted to single populations, although a few haplotypes are shared broadly
      across geography. Individual populations are typically comprised of haplotype
      sets from different branches in a network of relationships. Analysis of molecular
      variance (amova) indicates that approximately half of the total pool of variation
      is contained among individuals within local populations, and that only about 25%
      can be explained by the regional subdivisions of current subspecies distributions
      or physiographic realms. A hypothesized historical vicariant event that has been
      causally linked to the phylogeographical structure of other, codistributed
      species has had little influence on these pocket gopher populations, explaining
      only 13% of the total variation. The temporal depth, estimated by coalescence
      parameters, of the haplotype lineage in Baja California is relatively recent,
      approximately 300,000 generations; both the mismatch distribution of pairwise
      comparisons and a significantly positive exponential growth estimate support a
      recent history of expanding populations; but current, or recent past, migration
      estimates have remained small, are largely unidirectional from north to south,
      and weak isolation by distance is present. All data suggest that pocket gophers
      have relatively recently invaded the southern half of peninsular Baja California,
      with the genetic signature of expansion still evident but with sufficient time
      having lapsed to result in a weak isolation by distance pattern. The geographical
      assemblage of sampled populations thus appears as a meta-population, with limited
      gene flow contrasting with random haplotype loss due to drift in small, localized
      populations.

PMID- 15245403
TI  - Phylogeographical patterns in the American Pacific Northwest: lessons from the
      arionid slug Prophysaon coeruleum.
AB  - Some of the earliest studies of phylogenetic concordance involve native plants
      from the Pacific Northwest where many taxa showed clear genetic breaks between
      southern and northern populations. To test whether similar breaks also occur in
      invertebrate species with low dispersal capacities, genetic data from two
      mitochondrial genes are assembled for individuals of the arionid slug Prophysaon
      coeruleum throughout the species' range. Bayesian inference revealed three major
      clades and a total of eight subclades. It is argued that the demographic and
      genealogical past of P. coeruleum has resulted in a deep and shallow
      phylogeographical structure. The deep structure is at least 2.6-5.9 million years
      old and therefore clearly predates the Pleistocene period. Superimposed on this
      structure is a shallow structure that is most likely less than 2 million years
      old and probably the result of Pleistocene perturbations. Molecular analyses
      revealed that the three known colour traits in P. coeruleum do not represent
      monophyletic groups and that they do not match the patterns of genetic structure
      found. It is argued that the colour traits are perhaps a response to different
      levels of UV-radiation. The study adds to the increasing evidence that the
      phylogeographical structure of some taxa is more complex than previously thought.
      Moreover, it shows that genealogical concordance should not be deduced from
      phylogeographical patterns alone but should be based on an understanding of
      timing and causes of historical processes that lead to those patterns.

PMID- 15245404
TI  - Nest architecture and genetic differentiation in a species complex of Australian
      stingless bees.
AB  - We investigated the taxonomic significance of nest shape and its putative role in
      speciation in Trigona (Heterotrigona) carbonaria and T. (H.) hockingsi, two
      sibling species of stingless bee species from eastern Australia. These species
      are primarily distinguished by their nest architecture, as in all other respects
      they are nearly identical. We genotyped 130 colonies from six locations in
      Queensland at 13 microsatellite loci together with 106 additional colonies from
      six other Indo-Pacific Trigona species. Whether they were present in allopatry or
      in sympatry, colonies that displayed the T. carbonaria or the T. hockingsi nest
      architecture could be unambiguously differentiated at the genetic level. However,
      T. hockingsi colonies were classifiable into two highly differentiated
      paraphyletic and geographically separate populations, one in northern and one in
      southern Queensland. These two populations probably belong to two distinct
      species, T. hockingsi and T. davenporti nov. sp. Our results suggest that nest
      architecture characters are relevant but not sufficient criteria to identify
      species in this group. Consequently, modifications of nest architecture are
      probably not of prime importance in the speciation process of Australian
      stingless bees, although nest architecture differences probably result from
      relatively simple mechanisms. The rare interspecific hybrid colonies detected did
      not display a nest with an intermediate form between T. hockingsi and T.
      carbonaria.

PMID- 15245405
TI  - Red to Mediterranean Sea bioinvasion: natural drift through the Suez Canal, or
      anthropogenic transport?
AB  - The biota of the eastern basin of the Mediterranean Sea has experienced dramatic
      changes in the last decades, in part as a result of the massive invasion of Red
      Sea species. The mechanism generally hypothesized for the 'Red-to-Med' invasion
      is that of natural dispersal through the Suez Canal. To date, however, this
      hypothesis has not been tested. This study examines the mode of invasion, using
      as a model the mussel Brachidontes pharaonis, an acclaimed 'Lessepsian migrant'
      that thrives along the eastern Mediterranean coast. Our findings reveal two
      distinct lineages of haplotypes, and five possible explanations are discussed for
      this observation. We show that the genetic exchange among the Mediterranean, Gulf
      of Suez and the northern Red Sea is sufficiently large to counteract the build up
      of sequential genetic structure. Nevertheless, these basins are rich in unique
      haplotypes of unknown origin. We propose that it is historic secondary contact,
      an ongoing anthropogenic transport or both processes, that participate in driving
      the population dynamics of B. pharaonis in the Mediterranean and northern Red
      Sea.

PMID- 15245406
TI  - Global population structure and taxonomy of the wandering albatross species
      complex.
AB  - A recent taxonomic revision of wandering albatross elevated each of the four
      subspecies to species. We used mitochondrial DNA and nine microsatellite markers
      to study the phylogenetic relationships of three species (Diomedea antipodensis,
      D. exulans and D. gibsoni) in the wandering albatross complex. A small number of
      samples from a fourth species, D. dabbenena, were analysed using mitochondrial
      DNA only. Mitochondrial DNA sequence analyses indicated the presence of three
      distinct groups within the wandering albatross complex: D. exulans, D. dabbenena
      and D. antipodensis/D. gibsoni. Although no fixed differences were found between
      D. antipodensis and D. gibsoni, a significant difference in the frequency of a
      single restriction site was detected using random fragment length polymorphism.
      Microsatellite analyses using nine variable loci, showed that D. exulans, D.
      antipodensis and D. gibsoni were genetically differentiated. Despite the
      widespread distribution of D. exulans, we did not detect any genetic
      differentiation among populations breeding on different island groups. The lower
      level of genetic differentiation between D. antipodensis and D. gibsoni should be
      reclassified as D. antipodensis. Within the context of the current taxonomy,
      these combined data support three species: D. dabbenena, D. exulans and D.
      antipodensis.

PMID- 15245407
TI  - Genetic structure of nest aggregations and drone congregations of the southeast
      Asian stingless bee Trigona collina.
AB  - In stingless bees, sex is determined by a single complementary sex-determining
      locus. This method of sex determination imposes a severe cost of inbreeding
      because an egg fertilized by sperm carrying the same sex allele as the egg
      results in a sterile diploid male. To explore how reproductive strategies may be
      used to avoid inbreeding in stingless bees, we studied the genetic structure of a
      population of 27 colonies and three drone congregations of Trigona collina in
      Chanthaburi, Thailand. The colonies were distributed across six nest
      aggregations, each aggregation located in the base of a different fig tree.
      Genetic analysis at eight microsatellite loci showed that colonies within
      aggregations were not related. Samples taken from three drone congregations
      showed that the males were drawn from a large number of colonies (estimated to be
      132 different colonies in our largest swarm). No drone had a genotype indicating
      that it could have originated from the colony that it was directly outside.
      Combined, these results suggest that movements of drones and possibly movements
      of reproductive swarms among colony aggregations provide two mechanisms of
      inbreeding avoidance.

PMID- 15245409
TI  - Colony structure and parentage in wild colonies of co-operatively breeding
      Damaraland mole-rats suggest incest avoidance alone may not maintain reproductive
      skew.
AB  - Colonies of co-operatively breeding African mole-rats have traditionally been
      thought to be composed of a single breeding female, one or two breeding males,
      and their offspring. In the naked mole-rat (Heterocephalus glaber), the
      occurrence of facultative inbreeding means incest avoidance cannot prevent
      reproduction in subordinate group members, and physiological suppression of
      reproductive function by the breeding female occurs in both sexes. In contrast,
      previous studies of captive colonies of the Damaraland mole-rat (Cryptomys
      damarensis) suggest that breeding within a colony is restricted to a single
      breeding pair, simply because all other colony members are highly related (first-
      or second-order relatives) and this species is an obligate outbreeder. Using
      microsatellite markers, we investigated parentage and colony composition in 18
      wild Damaraland mole-rat colonies to determine whether inbreeding avoidance alone
      can explain the high levels of reproductive skew in this species. Multiple and
      unidentified paternity was widespread within colonies and immigrants of both
      sexes were regularly identified. Unrelated, opposite-sex nonbreeders were found
      coexisting in two colonies. These results suggest that, in the wild, conditions
      exist where nonreproductive females can come into contact with unrelated males,
      even when they do not disperse from their natal colony. Inbreeding avoidance
      alone is therefore insufficient to maintain the high levels of reproductive skew
      identified in this species suggesting that the breeding female somehow suppresses
      the reproductive function in nonbreeding females.

PMID- 15245408
TI  - Patterns of parental relatedness and pup survival in the grey seal (Halichoerus
      grypus).
AB  - Levels of parental relatedness can affect offspring survival and susceptibility
      to disease. We investigated parental relatedness of live and dead Halichoerus
      grypus pups between and within island populations and between possible causes of
      mortality. Nine microsatellites were used to calculate internal relatedness (IR)
      and standardized mean d2. We find that pups with higher than average levels of IR
      have significantly lower survival and that this varied between island populations
      and that certain loci contributed to the effect more than others. Although, there
      were no significant differences between causes of mortality, peritonitis,
      infection and stillborn had the highest levels of IR. These results provide
      evidence that parental relatedness is an important determinant of pre-weaning pup
      survival in the grey seal and that this may vary with cause of mortality given a
      larger sample size.

PMID- 15245410
TI  - Extreme queen-mating frequency and colony fission in African army ants.
AB  - Army ants have long been suspected to represent an independent origin of multiple
      queen-mating in the social Hymenoptera. Using microsatellite markers, we show
      that queens of the African army ant Dorylus (Anomma) molestus have the highest
      absolute (17.3) and effective (17.5) queen-mating frequencies reported so far for
      ants. This confirms that obligate multiple queen-mating in social insects is
      associated with large colony size and advanced social organization, but also
      raises several novel questions. First, these high estimates place army ants in
      the range of mating frequencies of honeybees, which have so far been regarded as
      odd exceptions within the social Hymenoptera. Army ants and honeybees are
      fundamentally different in morphology and life history, but are the only social
      insects known that combine obligate multiple mating with reproduction by colony
      fission and extremely male-biased sex ratios. This implies that the very high
      numbers of matings in both groups may be due partly to the relatively low costs
      of additional matings. Second, we were able to trace recent events of colony
      fission in four of the investigated colonies, where the genotypes of the two
      queens were only compatible with a mother-daughter relationship. A direct
      comparison of male production between colonies with offspring from one and two
      queens, respectively, suggested strongly that new queens do not produce a sexual
      brood until all workers of the old queen have died, which is consistent with kin
      selection theory.

PMID- 15245411
TI  - DNA analysis on fox faeces and competition induced niche shifts.
AB  - Interference competition can force inferior competitors to change their
      distribution patterns. It is, however, possible that the dominant competitor
      poses a higher threat during certain times of the year, for example during
      reproduction. In such cases, the inferior competitor is expected to change its
      distribution accordingly. We used a molecular species identification method on
      faeces to investigate how the spatial overlap between arctic and red foxes
      changes between seasons. The results show that arctic and red foxes are sympatric
      during winter, but allopatric in summer as arctic foxes retreat to higher
      altitudes further from the tree-line during the breeding season.

PMID- 15245412
TI  - Differences in mycorrhizal preferences between two tropical orchids.
AB  - Orchids parasitize their mycorrhizal fungi and are dependent on them for seed
      germination. Controversy reigns over how specific the mycorrhizal association is
      in tropical species. Although there is little experimental evidence to support
      any viewpoint, some variation is known to exist. We compared mycorrhizal
      specificity and performance in two phylogenetically related epiphytic orchids
      from Puerto Rico, Tolumnia variegata and Ionopsis utricularioides (Oncidiinae) by
      integrating two techniques: phylogenetic analysis of mycorrhizal fungi based on
      nuclear ribosomal internal transcribed spacer (ITS) sequences, and symbiotic seed
      germination experiments. Most of the mycorrhizal isolates from T. variegata fell
      into four different clades of Ceratobasidium, while most of those from I.
      utricularioides were restricted to a single clade of the same genus. Seeds of T.
      variegata germinated equally well with fungi from both T. variegata and I.
      utricularioides, but seeds of I. utricularioides germinated significantly better
      with its own isolates. Seeds of I. utricularioides germinated and developed
      faster than those of T. variegata. Both the molecular phylogeny and the seed
      germination experiments showed that T. variegata is a generalist in its
      association with fungal symbionts. In contrast, I. utricularioides is more
      specialized and more effective at exploiting a specific fungal clade. Our data
      are consistent with the theoretical trade-offs between specialized and
      generalized interactions.

PMID- 15245413
TI  - Reproductive effects and geographical distributions of two Wolbachia strains
      infecting the Neotropical beetle, Chelymorpha alternans Boh. (Chrysomelidae,
      Cassidinae).
AB  - Wolbachia are maternally inherited endocellular bacteria known to alter insect
      host reproduction to facilitate their own transmission. Multiple Wolbachia
      infections are more common in tropical than temperate insects but few studies
      have investigated their dynamics in field populations. The beetle, Chelymorpha
      alternans, found throughout the Isthmus of Panama, is infected with two strains
      of Wolbachia, wCalt1 (99.2% of beetles) and wCalt2 (53%). Populations infected
      solely by the wCalt1 strain were limited to western Pacific Panama, whereas
      populations outside this region were either polymorphic for single (wCalt1) and
      double infections (wCalt1 + wCalt2) or consisted entirely of double infections.
      The wCalt2 strain was not found as a single infection in the wild. Both strains
      caused cytoplasmic incompatibility (CI). The wCalt1 strain caused weak CI
      (approximately 20%) and the double infection induced moderate CI (approximately
      70-90%) in crosses with uninfected beetles. The wCalt1 strain rescued about 75%
      of eggs fertilized by sperm from wCalt2 males. Based on the relationships of
      beetle mtDNA and infection status, maternal transmission, and repeated population
      sampling we determined that the double infection invaded C. alternans populations
      about 100,000 years ago and that the wCalt2 strain appears to be declining in
      some populations, possibly due to environmental factors. This may be the first
      study to demonstrate an association between widespread strain loss and
      environmental factors in the field.

PMID- 15245414
TI  - Individual variability in herbivore-specific elicitors from the plant's
      perspective.
AB  - Lepidopteran larvae oral secretions and regurgitant (R), which contain a plethora
      of potential elicitors, are known to dramatically change a plant's wound
      response. We demonstrate, with a detailed microarray and secondary metabolite
      analysis, that the two most abundant fatty acid-amino acid conjugates (FACs) in
      the R of the specialist herbivore Manduca sexta (Lepidoptera, Sphingidae) can
      account for all measured direct (trypsin proteinase inhibitor: TPI) and indirect
      (cis-alpha-bergamotene) defences, the endogenous jasmonic acid burst that elicits
      them, and 86% of the induced transcriptional changes (89% up and 83% down) in its
      native host Nicotiana attenuata and hence are necessary and sufficient for the
      Manduca-specific modulation of the wound response. FACs were not found in eggs,
      but detected in larvae of all instars after their first meal. FACs were found in
      all regions of the alimentary canal and in the frass, but did not occur in
      salivary or mandibular glands, extracts of which were not active in any assay.
      Individual larvae differed substantially in their FAC composition and two FAC
      chemotypes were discernible: N-linolenoyl-L-glutamine biased R and N-linolenoyl-L
      glutamate biased R. We created synthetic blends of FACs to mimic these chemical
      phenotypes and determined whether plants respond differently to the different R
      chemotypes. Micorarray and TPI analysis revealed that plants do not
      differentiate. N. attenuata plants use FACs from feeding caterpillars to tailor
      their wound responses but do not use the variability in FAC ratios to recognize
      attack from an individual caterpillar.

PMID- 15245415
TI  - Diversity and specificity of Rhizobium leguminosarum biovar viciae on wild and
      cultivated legumes.
AB  - The symbiotic partnerships between legumes and their root-nodule bacteria
      (rhizobia) vary widely in their degree of specificity, but the underlying reasons
      are not understood. To assess the potential for host-range evolution, we have
      investigated microheterogeneity among the shared symbionts of a group of related
      legume species. Host specificity and genetic diversity were characterized for a
      soil population of Rhizobium leguminosarum biovar viciae (Rlv) sampled using six
      wild Vicia and Lathyrus species and the crop plants pea (Pisum sativum) and broad
      bean (Vicia faba). Genetic variation among 625 isolates was assessed by
      restriction fragment length polymorphism (RFLP) of loci on the chromosome
      (ribosomal gene spacer) and symbiosis plasmid (nodD region). Broad bean strongly
      favoured a particular symbiotic genotype that formed a distinct phylogenetic
      subgroup of Rlv nodulation genotypes but was associated with a range of
      chromosomal backgrounds. Host range tests of 80 isolates demonstrated that only
      34% of isolates were able to nodulate V. faba. By contrast, 89% were able to
      nodulate all the local wild hosts tested, so high genetic diversity of the
      rhizobial population cannot be ascribed directly to the diversity of host species
      at the site. Overall the picture is of a population of symbionts that is
      diversified by plasmid transfer and shared fairly indiscriminately by local wild
      legume hosts. The crop species are less promiscuous in their interaction with
      symbionts than the wild legumes.

PMID- 15245416
TI  - Identity and diversity of coral endosymbionts (zooxanthellae) from three Palauan
      reefs with contrasting bleaching, temperature and shading histories.
AB  - The potential of corals to associate with more temperature-tolerant strains of
      algae (zooxanthellae, Symbiodinium) can have important implications for the
      future of coral reefs in an era of global climate change. In this study, the
      genetic identity and diversity of zooxanthellae was investigated at three reefs
      with contrasting histories of bleaching mortality, water temperature and shading,
      in the Republic of Palau (Micronesia). Single-stranded conformation polymorphism
      and sequence analysis of the ribosomal DNA internal transcribed spacer (ITS)1
      region was used for genotyping. A chronically warm but partly shaded coral reef
      in a marine lake that is hydrographically well connected to the surrounding
      waters harboured only two single-stranded conformation polymorphism profiles
      (i.e. zooxanthella communities). It consisted only of Symbiodinium D in all 13
      nonporitid species and two Porites species investigated, with the remaining five
      Porites harbouring C*. Despite the high temperature in this lake (> 0.5 degrees
      above ambient), this reef did not suffer coral mortality during the (1998)
      bleaching event, however, no bleaching-sensitive coral families and genera occur
      in the coral community. This setting contrasts strongly with two other reefs with
      generally lower temperatures, in which 10 and 12 zooxanthella communities with
      moderate to low proportions of clade D zooxanthellae were found. The data
      indicate that whole coral assemblages, when growing in elevated seawater
      temperatures and at reduced irradiance, can be composed of colonies associated
      with the more thermo-tolerant clade D zooxanthellae. Future increases in seawater
      temperature might, therefore, result in an increasing prevalence of Symbiodinium
      phylotype D in scleractinian corals, possibly associated with a loss of diversity
      in both zooxanthellae and corals.

PMID- 15245417
TI  - Variation of female frequency and cytoplasmic male-sterility gene frequency among
      natural gynodioecious populations of wild radish (Raphanus sativus L.).
AB  - In gynodioecious plant populations, sex determination often involves both
      cytoplasmic male-sterility (CMS) genes and specific nuclear genes that restore
      male function. How gynodioecy is maintained under the joint dynamics of CMS and
      restorer genes remains controversial. Although many theoretical models deal with
      interactions between CMS genes and restorer genes with sexual phenotypes and
      predict changes in their frequencies, it is difficult to observe the frequencies
      because no molecular markers have been established for either CMS or restorer
      genes in well-studied gynodioecious plants. This is the first report of the
      frequency of a CMS gene determined using a molecular marker in natural
      populations of a gynodioecious plant. Using a set of CMS gene-specific polymerase
      chain reaction primers, we compared female and CMS gene frequencies in 18 natural
      populations of Raphanus sativus. Female frequency was relatively low, ranging
      from 0 to 0.21. In contrast, the CMS gene frequency was highly variable among
      populations, ranging from 0 to 1. Estimated restorer gene frequency seemed less
      variable than observed CMS gene frequency, probably due to higher gene flow than
      in the CMS gene. Genetic drift may play a role in maintaining high variability of
      the CMS gene, although other possibilities are not excluded.

PMID- 15245418
TI  - No evidence of an MHC-based female mating preference in great reed warblers.
AB  - Female mate-choice based on genetic compatibility is an area of growing interest.
      The major histocompatibility complex (MHC) genes are likely candidates for such
      mate-choice since these highly polymorphic genes may both increase offspring
      viability and also provide direct cues for mate-choice. In great reed warblers,
      females actively choose a breeding partner out of a handful of males that they
      visit and evaluate; thus, female preference for compatible or heterozygous MHC
      genes could have evolved. Here, I investigate whether great reed warbler females
      preferentially mate with males with dissimilar MHC class I alleles or with males
      that are heterozygous at MHC class I. Despite favourable conditions, a thorough
      screening method and a large sample size, there was no evidence of an MHC-based
      female mating preference based on either genetic compatibility or heterozygosity
      in this population. Power analyses of the data sets revealed that relatively
      small differences (15% and 8%, respectively) between true and random pairs should
      have been detected.

PMID- 15245419
TI  - Hybridization and contemporary evolution in an introduced cichlid fish from Lake
      Malawi National Park.
AB  - Rapidly evolving systems offer the chance to observe genetic and phenotypic
      change in real time. We exploit a well-characterized introduction of cichlid fish
      into Lake Malawi National Park to document a short history of habitat
      colonization and the evolution of genes and colour pattern. In the early 1960s, a
      fish exporter introduced individuals of Cynotilapia afra to a single site
      (Mitande Point) of Thumbi West Island and, as late as 1983, the species was
      confined to this location. In 2001, C. afra had colonized the entire perimeter of
      Thumbi West. In July of that year, we sampled C. afra individuals from six sites
      around the island and scored variation in dorsal fin colour as well as allelic
      diversity at six microsatellite loci. We found that, in two decades, C. afra had
      diverged into genetically distinct, phenotypically different northern and
      southern populations. We observed a high proportion of hybrids between the
      introduced C. afra and the native Metriaclima zebra on the southern coast of
      Thumbi West, and speculate that hybridization is facilitated by low water clarity
      at these windward sites. The short history of C. afra at Thumbi West is a
      microcosm of contemporary evolutionary divergence and may provide the opportunity
      to study the process from start to finish in genetic detail.

PMID- 15245420
TI  - Climate and habitat barriers to dispersal in the highly mobile grey wolf.
AB  - We reanalysed published data to evaluate whether climate and habitat are barriers
      to dispersal in one of the most mobile and widely distributed mammals, the grey
      wolf (Canis lupus). Distance-based redundancy analysis (dbRDA) was used to
      examine the amount of variation in genetic distances that could be explained by
      an array of environmental factors, including geographical distance. Patterns in
      genetic variation were also examined using MDS plots among populations and
      relationships between genetic structure and individual environmental variables
      were further explored using the BIOENV procedure. We found that, contrary to a
      previous report, a pattern of isolation with distance is evident on a continental
      scale in the North American wolf population. This pattern is apparently related
      to climate and habitat. Specifically, vegetation types appear to play a role in
      the genetic dissimilarities among populations. When we controlled for the effect
      of spatial variation, climate was still associated with genetic distance.
      Further, partitioning of geographical distances into latitudinal and longitudinal
      axes revealed that the east-west gradient had the strongest relationship with
      genetic distance. We suggest two possible mechanisms by which environmental
      conditions may influence the dispersal decisions made by wolves.

PMID- 15245421
TI  - World-wide survey of an Accord insertion and its association with DDT resistance
      in Drosophila melanogaster.
AB  - Previous work showed that insecticide resistance in Drosophila melanogaster is
      correlated with the insertion of an Accord-like element into the 5' region of the
      cytochrome P450 gene, Cyp6g1. Here, we study the distribution of the Accord-like
      element in 673 recently collected D. melanogaster lines from 34 world-wide
      populations. We also examine the extent of microsatellite variability along a 180
      kilobase (kb) genomic region of chromosome II encompassing the resistance gene.
      We confirm a 100% correlation of the Accord insertion with insecticide resistance
      and a significant reduction in variability extending at least 20 kb downstream of
      the Cyp6g1 gene. The frequency of the Accord insertion differs significantly
      between East African (32-55%) and nonAfrican (85-100%) populations. This pattern
      is consistent with a selective sweep driving the Accord insertion close to
      fixation in nonAfrican populations as a result of the insecticide resistance
      phenotype it confers. This study confirms that hitchhiking mapping can be used to
      identify beneficial mutations in natural populations.

PMID- 15245422
TI  - Update on graft versus host disease.

PMID- 15245423
TI  - Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes
      Aldh1a2 and Aldh1a3 indicate complex regulation.
AB  - Retinoic acid has long been known to alter skin and hair growth but an exact
      mechanism is unclear. This study was performed to examine the sites of endogenous
      retinoic acid synthesis in the cycling hair follicle to better understand the
      role retinoic acid plays in this process. Retinal dehydrogenases (Aldh1a1, 2, and
      3, formerly Raldh 1, 2, and 3) are the enzymes responsible for the last step in
      retinoic acid synthesis. Immunohistochemistry was performed on adult C57BL/6J
      mouse skin sections with antibodies against Aldh1a2 and Aldh1a3. Aldh1a2
      expression was seen primarily in the outer root sheath and basal/spinous layer
      during all stages of the hair cycle, and in the bulge during anagen and early
      catagen, whereas Aldh1a3 expression was primarily in the dermal papilla, pre
      cortex, and hair shaft during mid-late anagen. The expression patterns of these
      two similar retinoic acid synthesizing enzymes at specific follicular sites
      suggest that they mediate and are regulated by different epithelial proliferation
      and differentiation signaling pathways.

PMID- 15245424
TI  - Characterization of Lef-1 promoter segments that facilitate inductive
      developmental expression in skin.
AB  - Lymphoid Enhancer Factor 1 (Lef-1) is an important developmental transcription
      factor required for the inductive formation of several epithelial-derived organs
      including hair follicles. Inductive expression of Lef-1 mRNA is tightly regulated
      during embryo development, suggesting the involvement of a highly regulated
      promoter. In vitro analysis of the Lef-1 gene has demonstrated the existence of
      at least two spatially distinct promoters with multiple transcriptional start
      sites that are responsive to the canonical Wnt/beta-catenin pathway. Regions of
      the Lef-1 promoter required for inductive regulation in vivo, however, have yet
      to be determined. To this end, we utilized LacZ-reporter transgenic mice to
      define segments of the human Lef-1 promoter capable of reproducing mesenchymal-
      or epithelial-restricted transcriptional patterns of Lef-1 expression during hair
      and vibrissa follicle development. These studies have revealed that a 110 bp
      Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1
      promoter, plays an important role in regulating mesenchymal, and potentially
      epithelial, expression during follicle development in mouse embryos. This 2.5 kb
      Lef-1 promoter also demonstrated inductive mesenchymal expression during
      postnatal anagen stage hair-follicle cycling. Additionally, analysis of Lef-1
      promoter expression revealed previously uncharacterized regions of endogenous Lef
      1 expression seen in the sebaceous glands of vibrissa and hair follicles in
      transgenic lines harboring the minimal Lef-1 promoter and additional intronic
      sequences. In summary, these studies have begun to dissect the transcriptional
      diversity of the human Lef-1 promoter during the hair/vibrissa follicle and
      sebaceous gland formation.

PMID- 15245425
TI  - Expression of Frizzled genes in developing and postnatal hair follicles.
AB  - Embryonic hair follicle development and postnatal hair growth rely on
      intercellular communication within the epithelium and between epithelial and
      mesenchymal cells. Several members of the WNT family of paracrine intercellular
      signaling molecules are expressed in specific subsets of cells in developing and
      mature mouse hair follicles, suggesting them as candidates for some of the
      intercellular signals that operate in these organs. As WNT ligands activate
      several different signaling pathways, they may play multiple and complex roles in
      developing and postnatal skin. To begin to investigate these functions, we have
      used in situ hybridization to identify cells that express Frizzled (Fz) WNT
      receptor genes, and so are potentially receptive to WNT ligands. We find that
      several Fz genes are specifically expressed at sites of known activity of the
      WNT/beta-catenin signaling pathway, allowing us to identify candidate receptors
      for canonical WNT ligands important in appendage development. The expression of
      additional Fz genes is specifically elevated at locations and developmental
      stages other than those that display WNT/beta-catenin pathway activity,
      suggesting that signaling through alternate WNT pathways may contribute to the
      development and function of skin and hair.

PMID- 15245426
TI  - Expression profiles of tyrosine kinases in cultured follicular papilla cells
      versus dermal fibroblasts.
AB  - Tyrosine kinases play crucial roles in cell differentiation and proliferation.
      Using degenerative primed PCR followed by differential display, we analyzed the
      tyrosine kinase expression profiles of cultured rat follicular papilla (FP) cells
      versus dermal fibroblasts. We showed that c-met, cdc2, and tec were
      preferentially expressed in cultured FP cells, whereas alpha-platelet-derived
      growth factor receptor (alpha-PDGFR) was preferentially expressed in cultured
      fibroblasts. The cell type specificity of these tyrosine kinases was confirmed by
      semi-quantitative RT-PCR using both rat and human cultured cells. Consistent with
      these results, hepatocyte growth factor preferentially stimulated the growth of
      rat FP cells, whereas PDGF-AA preferentially stimulated rat fibroblasts. High
      concentrations of some these kinases are also found in the follicular matrix
      keratinocytes as revealed by in situ hybridization. The expression of specific
      tyrosine kinases in FP and matrix cells may play roles in regulating hair growth
      and cycling.

PMID- 15245427
TI  - A phenotype resembling the Clouston syndrome with deafness is associated with a
      novel missense GJB2 mutation.
AB  - Mutations in GJB2 (connexin26) are associated with skin disorders and deafness.
      The Clouston syndrome (MIM129500) is associated with mutations in GJB6
      (connexin30). Here, we describe a patient suffering from a Clouston-syndrome-like
      phenotype of thin hair, deafness, nail dystrophy, and mild erythrokeratoderma,
      caused by a novel spontaneous missense mutation in GJB2. The heterozygous
      mutation in codon 42, AAC>AAG, changes asparagine to lysine (N14K).
      Interestingly, this asparagine is near two of the residues mutated in Keratitis
      like ichthyosis deafness (KID) syndrome (G12R and S17F), yet the phenotype
      associated with N14K strongly differs from the KID phenotype. Instead, there is a
      clear phenotypic overlap with syndromes associated with connexin26 or 30
      mutations. Our finding suggest that careful audiological evaluation of patients
      suffering from Clouston-syndrome-like phenotypes is warranted and expand the
      spectrum of connexin26-associated disease.

PMID- 15245428
TI  - Adult-onset Alopecia areata is a complex polygenic trait in the C3H/HeJ mouse
      model.
AB  - Alopecia areata (AA) is an autoimmune disease that targets actively growing
      (anagen) hair follicles in humans and other mammals. C3H/HeJ, but not C57BL/6J,
      mice spontaneously develop an adult-onset form of AA. A segregating population of
      C3HB6F2 female mice (n=1096), generated from crossing these two strains, was used
      for genome-wide linkage analysis to identify AA genetic susceptibility. Previous
      analysis identified susceptibility intervals on chromosomes 17 (Alaa1) and 9
      (Alaa2). Using additional markers in these intervals and saturation mapping
      purported intervals on chromosomes 8 and 15, two additional regions were
      identified (Alaa3 and Alaa4, respectively). Human gene association studies
      identified specific human leukocyte antigen intervals comparable with those
      (major histocompatibility complex) found in Alaa1 in the mouse. Other human
      studies identified genes not found in this linkage study, but these human
      transcription factors are directly regulated by genes within Alaa1. These results
      indicate the necessity of integrating both gene association and genome-wide
      linkage studies in both mice and humans to understand the complex nature of these
      and other polygenic diseases.

PMID- 15245429
TI  - Human epidermal langerhans cells express the immunoregulatory enzyme indoleamine
      2,3-dioxygenase.
AB  - Langerhans cells (LC) are a special subset of dendritic cells integrating
      cutaneous immunity. The study of LC function is of major interest not only for
      efforts of vaccine design and immunotherapy but also for gaining an insight into
      the pathogenesis of immune-mediated cutaneous diseases and neoplasias. Recently,
      defined antigen-presenting cells were described that express indoleamine 2,3
      dioxygenase (IDO) and inhibit T cell proliferation in vitro and in vivo. Here, we
      show that stimulation with interferon-gamma (IFN-gamma) induces the expression of
      functionally active IDO in highly purified human epidermal LC. The induction of
      IDO after stimulation of LC with IFN-gamma seems to follow a defined kinetic with
      rapid upregulation followed by a downregulation after about 24 h of culture.
      Accordingly, proliferation of T cells induced by anti-CD3 antibodies was
      modulated by supernatants of IFN-gamma-activated human epidermal LC. Importantly,
      downregulation of T cell proliferation by supernatants of 24 h IFN-gamma
      activated LC was prevented by inhibition of IDO. These results indicate that LC
      not only have the capacity to stimulate but also to inhibit T cells, and suggest
      that LC possess an immunoregulatory function in promoting T cell tolerance by
      production of IDO.

PMID- 15245430
TI  - Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates
      keratinocyte differentiation.
AB  - Previous studies demonstrated that peroxisome-proliferator-activated receptor
      (PPAR)-alpha or PPAR-delta activation stimulates keratinocyte differentiation, is
      anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that
      treatment of cultured human keratinocytes with ciglitazone, a PPAR-gamma
      activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover,
      topical treatment of hairless mice with ciglitazone or troglitazone increases
      loricrin, involucrin, and filaggrin expression without altering epidermal
      morphology. These results indicate that PPAR-gamma activation stimulates
      keratinocyte differentiation. Additionally, PPAR-gamma activators accelerated
      barrier recovery following acute disruption by either tape stripping or acetone
      treatment, indicating an improvement in permeability barrier homeostasis.
      Treatment with PPAR-gamma activators also reduced the cutaneous inflammatory
      response that is induced by phorbol 12-myristate-13-acetate, a model of irritant
      contact dermatitis and oxazolone, a model of allergic contact dermatitis. To
      determine whether the effects of PPAR-gamma activators are mediated by PPAR
      gamma, we next examined animals deficient in PPAR-gamma. Mice with a deficiency
      of PPAR-gamma specifically localized to the epidermis did not display any
      cutaneous abnormalites on inspection, but on light microscopy there was a modest
      increase in epidermal thickness associated with an increase in proliferating cell
      nuclear antigen (PCNA) staining. Key functions of the skin including permeability
      barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and
      response to inflammatory stimuli were not altered in PPAR-gamma-deficient
      epidermis. Although PPAR-gamma activators stimulated loricrin and filaggrin
      expression in wild-type animals, however, in PPAR-gamma-deficient mice no effect
      was observed indicating that the stimulation of differentiation by PPAR-gamma
      activators is mediated by PPAR-gamma. In contrast, PPAR-gamma activators
      inhibited inflammation in both PPAR-gamma-deficient and wild-type mouse skin,
      indicating that the inhibition of cutaneous inflammation by these PPAR-gamma
      activators does not require PPAR-gamma in keratinocytes. These observations
      suggest that thiazolidindiones and perhaps other PPAR-gamma activators maybe
      useful in the treatment of cutaneous disorders.

PMID- 15245431
TI  - Tetracycline-regulated transactivators driven by the involucrin promoter to
      achieve epidermal conditional gene expression.
AB  - To achieve conditional gene expression in the differentiated layers of the
      epidermis, we generated transgenic mice with the tetracycline-regulated
      transactivator proteins, tTA (tetracycline transactivator) and rtTA (reverse
      tetracycline transactivator), expressed from the human involucrin promoter.
      Interaction with tetracycline turns off or turns on the tTA and rtTA molecules,
      respectively, allowing for regulation of downstream target genes during
      development and postnatally. These transactivator lines were crossed with
      reporter mice driving LacZ expression from a tetracycline response element to
      analyze the specificity and levels of target gene expression. Quantitative beta
      galactosidase experiments demonstrate a 30-fold induction, specific to epithelial
      tissues. Immunohistochemistry results illustrate that the beta-galactosidase
      staining follows that of endogenous involucrin expression. Induction initiates at
      embryonic day 14.5 with expression over the entire epidermal surface by E16.5.
      Together with other driver lines, expressing tetracycline transactivators in the
      mitotically active layers of the epidermis, these mice will allow investigators
      to specifically modulate expression of target genes to specific stages of
      epidermal differentiation.

PMID- 15245432
TI  - 17beta-estradiol stimulates the growth of human keratinocytes by inducing cyclin
      D2 expression.
AB  - Estrogen is reported to prevent age-associated epidermal thinning in the skin. We
      examined if 17beta-estradiol (E2) may enhance the growth of human keratinocytes,
      focusing on its effects on the expression of cell cycle-regulatory proteins. E2
      enhanced proliferation, bromodeoxyuridine incorporation of keratinocytes, and
      increased the proportion of cells in the S phase. The E2-induced stimulation of
      proliferation and bromodeoxyuridine incorporation was suppressed by antisense
      oligonucleotide against cyclin D2, which induces G1 to S phase progression. E2
      increased protein and mRNA levels of cyclin D2, and resultantly enhanced assembly
      and kinase activities of cyclin D2-cyclin-dependent kinases 4 or 6 complexes. E2
      enhanced cyclin D2 promoter activity, and the element homologous to cAMP response
      element (CRE) on the promoter was responsible for the effect. Cyclin D2
      expression was enhanced by antiestrogens, ICI 182,780 and 4-hydroxytamoxifen, and
      membrane-impermeable bovine serum albumin-conjugated E2, indicating the effects
      via membrane E2-binding sites. E2 increased the enhancer activity of CRE-like
      element and the amount of phosphorylated cAMP response element binding protein
      (CREB) binding this element, and the increases were suppressed by H-89, an
      inhibitor of cAMP-dependent protein kinase A. H-89 also suppressed E2-induced
      cyclin D2 expression, proliferation, and bromodeoxyuridine incorporation in
      keratinocytes. Antisense oligonucleotide against G-protein-coupled receptor GPR30
      suppressed the E2-induced increases of phosphorylated CREB, cyclin D2 level,
      proliferation, and bromodeoxyuridine incorporation in keratinocytes. These
      results suggest that E2 may stimulate the growth of keratinocytes by inducing
      cyclin D2 expression via CREB phosphorylation by protein kinase A, dependent on
      cAMP. These effects of E2 may be mediated via cell surface GPR30.

PMID- 15245433
TI  - 17beta-estradiol enhances the production of granulocyte-macrophage colony
      stimulating factor in human keratinocytes.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is effective for
      impaired wound repair. Estrogen is known to enhance wound repair. We examined if
      17beta-estradiol (E2) may in vitro enhance GM-CSF production in human
      keratinocytes. E2 and membrane-impermeable bovine serum albumin-conjugated E2
      increased GM-CSF secretion, mRNA stability, and promoter activity. The element
      homologous to activator protein-1 (AP-1) on the promoter was responsible for the
      activation. E2 enhanced transcriptional activity and DNA binding of AP-1. E2
      transiently generated c-Fos protein, and shifted AP-1 composition from c-Jun
      homodimers to c-Fos/c-Jun heterodimers in keratinocytes. E2-induced enhancement
      of GM-CSF secretion, mRNA stability, and promoter activity were not suppressed by
      estrogen receptor antagonist ICI 182,780, however, suppressed by conventional
      protein kinase C inhibitor Go6976 and PD98059, an inhibitor of mitogen-activated
      protein kinase kinase (MEK). Go6976 and PD98059 suppressed E2-induced c-Fos
      expression and enhancement of DNA-binding and transcriptional activity at AP-1.
      E2 induced membrane translocation of protein kinase Calpha, which was suppressed
      by phosphatidylinositol (PI)-specific phospholipase C (PLC) inhibitor U73122. E2
      stimulated the phosphorylation of extracellular signal-regulated kinase (ERK),
      which was suppressed by PD98059, Go6976, and U73122. E2 transiently generated
      inositol 1,4,5-triphosphate in keratinocytes, which was suppressed by U73122 and
      guanine nucleotide-binding protein inhibitor. These results suggest that E2 may
      enhance GM-CSF production via guanine nucleotide-binding protein-coupled membrane
      receptors and signaling cascade of PI-specific PLC/protein kinase Calpha/MEK/ERK.

PMID- 15245434
TI  - Human leukocyte elastase induces keratinocyte proliferation by epidermal growth
      factor receptor activation.
AB  - Epidermal hyperproliferation and neutrophil infiltration are major
      histopathological changes observed in psoriasis. Neutrophils contain human
      leukocyte elastase (HLE), which is released at sites of inflammation. HLE is
      present in psoriatic lesions and induces keratinocyte hyperproliferation in vitro
      and in vivo. To determine the molecular mechanisms linking a proteolytic effect
      of HLE and epidermal hyperproliferation, we examined the effects of HLE-induced
      signaling in human keratinocytes. Application of 100 nM HLE resulted in a
      transient calcium influx in FURA2-loaded human HaCaT keratinocytes observed by
      single-cell fluorescence imaging. The calcium signal was concentration dependent
      and was inhibited by addition of the HLE inhibitors elafin and secretory
      leukocyte protease inhibitor. The calcium signal was neither inhibited by
      pertussis toxin, cholera, or by pre-stimulation with trypsin. Incubation with the
      tyrosine kinase inhibitor genistein, a protein kinase C inhibitor, as well as
      incubation with neutralizing EGFR antibodies abolished the HLE-induced calcium
      influx. The supernatants of HLE-treated keratinocytes induced a calcium signal in
      separately cultured keratinocytes. This could be inhibited by the addition of
      anti-TGF-alpha antibodies. Application of HLE-induced keratinocyte proliferation,
      which could be inhibited by neutralizing of anti-EGFR and anti-TGF-alpha
      antibodies. Herein we demonstrate that HLE induces keratinocyte proliferation by
      proteolytic activation of an EGFR signaling cascade involving TGF-alpha.

PMID- 15245436
TI  - UV light from 290 to 325 nm, but not broad-band UVA or visible light, augments
      the formation of melanocytic nevi in a guinea-pig model for human nevi.
AB  - We have previously described a guinea-pig model where pigmented nevi similar to
      human nevi can be produced by application of low-dose topical 7,12
      dimethylbenzanthracene (DMBA) followed by solar-simulated light. Five groups of
      guinea-pigs were used to test the effect of various spectral bands of solar
      simulated light on low-dose DMBA-induced melanocytic nevi. Animals were
      irradiated with either UVB to near UVA2 (290-325 nm), UVA, visible light, full
      solar spectrum or no irradiation three times per wk for 12 mo to determine the
      broad-band effect of nevi-inducing irradiation. There was a significant increase
      in nevi/animal in the UVB-treated group (mean 1.53) compared with all groups
      (versus UVA 0.3, p<0.001; versus visible light 0.24, p<0.001; versus full
      spectrum (UVB+UVA+visible) 0.68, p=0.02; versus control (nil irradiation) 0.37,
      p=0.01). No differences in skin thickness were found between any group (p=0.11).
      In conclusion, we present a report of the active waveband of melanocytic nevi
      induction; where UVB to near UVA2 is the likely responsible waveband.
      Furthermore, because there was a significant decrease in nevi/animal receiving
      the full solar spectrum compared with the UVB group, it is possible that broad
      band UVA and or visible light may be inhibitory wavebands for nevi induction.

PMID- 15245435
TI  - Autocrine catecholamine biosynthesis and the beta-adrenoceptor signal promote
      pigmentation in human epidermal melanocytes.
AB  - Earlier it has been shown that human proliferating/undifferentiated basal
      keratinocytes hold the full capacity for autocrine catecholamine
      synthesis/degradation and express beta2-adrenoceptors (beta2-AR). In this report,
      we show that human melanocytes also express all of the mRNA and enzymes for
      autocrine synthesis of norepinephrine but fail to produce epinephrine. So far, it
      was established that human melanocytes express alpha1-AR which are induced by
      norepinephrine yielding the inosine triphosphate diacylglycerol signal. The
      presence of catecholamine synthesis and the beta2-AR signal escaped definition at
      that time. Using RT-PCR, immunofluorescence and radioligand binding with the
      beta2-AR antagonist (-)-[3H]CGP 12177, we show here that human melanocytes
      express functional beta2-AR (4230 receptors per cell) with a Bmax at 129.3 and a
      KD of 3.19 nM but lack beta1-AR expression. beta2-AR stimulation with epinephrine
      10(-6) M and salbutamol 10(-6)-10(-5) M yielded a strong cyclic adenosine
      monophospate (cAMP) response in association with upregulated melanin production.
      Taken together these results indicate that the biosynthesis and release of
      epinephrine (10(-6) M) by surrounding keratinocytes can provide the cAMP response
      leading to melanogenesis in melanocytes via the beta2-AR signal. Moreover, the
      discovery of this catecholaminergic cAMP response in melanocytes adds a new
      source for this important second messenger in melanogenesis.

PMID- 15245437
TI  - p38 Mitogen-Activated protein kinase mediates dual role of ultraviolet B
      radiation in induction of maturation and apoptosis of monocyte-derived dendritic
      cells.
AB  - Although ultraviolet B (UVB) induces apoptosis and functional perturbations in
      dendritic cells (DC), for example, Langerhans cells (LC), it also stimulates some
      LC into maturation after irradiation in vivo. To analyze its reciprocal effects
      on DC, we elucidated the direct effect of UVB on DC in vitro using human monocyte
      derived DC (MoDC). UVB from 50 to 200 J per m2 stimulated the maturation of MoDC
      with (1) augmented expression of CD86 and HLA-DR, (2) enhanced production of IL
      1beta, IL-6, IL-8, and TNF-alpha at both the mRNA and protein levels, and (3)
      enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses
      induced apoptotic cell death. Western-blot analysis of MoDC after UVB
      demonstrated a concentration-dependent phosphorylation of p38- and c-JUN N
      terminal kinase (JNK)-mitogen-activated protein kinases (MAPK), but not that of
      extracellular signal-regulated kinases. p38 MAPK-inhibitor, SB203580, inhibited
      both UVB-induced maturation and apoptosis of MoDC. Interestingly, MoDC that had
      undergone apoptosis exhibited an augmented expression of HLA-DR without
      upregulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our
      study revealed a dual effect of UVB, to stimulate maturation or to induce
      apoptosis in MoDC, depending on the dosage, via p38 MAPK pathway.

PMID- 15245438
TI  - CpG motifs are efficient adjuvants for DNA cancer vaccines.
AB  - DNA vaccines can induce impressive specific cellular immune response (IR) when
      taking advantage of their recognition as pathogen-associated molecular patterns
      (PAMP) through Toll-like receptors (TLR) expressed on/in cells of the innate
      immune system. Among the many types of PAMP, immunostimulatory DNA, so-called CpG
      motifs, was shown to interact specifically with TLR9, which is expressed in
      plasmacytoid dendritic cells (pDC), a key regulatory cell for the activation of
      innate and adaptive IR. We now report that CpG motifs, when introduced into the
      backbone, are a useful adjuvant for plasmid-based DNA (pDNA) vaccines to induce
      melanoma antigen-specific protective T cell responses in the Cloudman M3/DBA/2
      model. The CpG-enriched pDNA vaccine induced protection against subsequent
      challenge with melanoma cells at significantly higher levels than its parental
      unmodified vector. Preferential induction of an antigen-specific, protective T
      cell response could be demonstrated by (i) induction of antigen-dependent tumor
      cell protection, (ii) complete loss of protection by in vivo CD4+/CD8+T cell- but
      not NK cell-depletion, and (iii) the detection of antigen-specific T cell
      responses but not of relevant NK cell activity in vitro. These results
      demonstrate that employing PAMP in pDNA vaccines improves the induction of
      protective, antigen-specific, T cell-mediated IR.

PMID- 15245439
TI  - The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9
      dien-28-oic acid) induces apoptosis in Mycosis fungoides/Sezary syndrome cells.
AB  - The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9
      dien-28-oic acid) can serve as a ligand for the peroxisome proliferator activator
      receptor-gamma (PPAR-gamma) and has been shown to inhibit cell proliferation, and
      to induce differentiation and apoptosis in tumor cell lines. Bexarotene is an RXR
      selective retinoid that can induce apoptosis of mycosis fungoides (MF) and Sezary
      syndrome (SS) cells. Since the PPAR-gamma and RXR receptors can form
      heterodimers, we studied the effects of CDDO and its synergism with bexarotene on
      apoptosis in MF/SS cell lines (MJ, Hut78, and HH) and freshly isolated peripheral
      blood lymphocytes (PBL) from SS patients with circulating atypical T cells
      (CD4+CD26-). CDDO treatment at 1-5 microM for 48 h caused a concentration
      dependent apoptosis in three MF/SS cell lines and patients' PBL compared to
      vehicle controls. Bexarotene augmented CDDO-induced apoptosis in these cells.
      PPAR-gamma was expressed but decreased by 47% in MJ, 42% in Hut78, and 77% in HH
      cells following CDDO treatment. The anti-apoptotic protein bcl-xL, but not bcl-2,
      was decreased by 69% in MJ, 31% in Hut78, and 59% in HH cells and caspase-3 was
      activated following CDDO treatment. Interestingly, the PPAR-gamma antagonist T007
      did not block CDDO-induced apoptosis, and the more potent PPAR-gamma agonist
      rosiglitazone required much higher concentrations (>50 microM) than CDDO to
      induce apoptosis in MF/SS cells. In summary, CDDO induces apoptosis that is
      further enhanced by bexarotene and decreases the PPAR-gamma and bcl-xL proteins
      in MF/SS cells. CDDO's effects on MF/SS cells may be at least partly mediated
      through a PPAR-gamma-independent mechanism. Our findings suggest the rationale
      for further investigation of the clinical potential of CDDO, either alone or in
      combination with bexarotene for MF/SS patients.

PMID- 15245440
TI  - High prevalence of cutaneous human papillomavirus DNA on the top of skin tumors
      but not in "Stripped" biopsies from the same tumors.
AB  - Genomes of human papillomaviruses (HPV) are common in biopsies from non-melanoma
      skin cancers but are also found on healthy skin and it is possible that HPV
      positivity in tumor biopsies by PCR may merely reflect contamination of the
      lesion surface. To investigate this issue, 229 immunocompetent patients were
      tested for HPV DNA in swab samples collected on top of skin tumors and in
      biopsies of the same tumors, obtained after stripping with tape to remove
      superficial layers. HPV DNA was detected on top of 69% (159 of 229) of the
      lesions, and in 12% (28 of 229) of the stripped biopsies (p<0.001). The
      difference was seen for all four types of tumors studied. Seborrheic keratosis
      had 79% (34 of 43) HPV positivity on top of lesions versus 19% (eight of 43) in
      biopsies; actinic keratosis had 83% (38 of 46) HPV positivity on top versus 11%
      (five of 46) in biopsies; basal cell carcinoma had 63% (69 of 109) on top versus
      8% (nine of 109) in biopsies and squamous cell carcinoma had 58% (18 of 31) on
      top versus 19% (six of 31) in biopsies. HPV DNA is common in superficial layers
      of lesions, but is not necessarily present throughout tumors.

PMID- 15245441
TI  - Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and
      metastasis of B16F10 melanoma cells.
AB  - Although melanoma mostly affects the skin, it is notorious for its propensity to
      easily develop metastasis. Metastatic melanoma is highly resistant to a variety
      of therapies. We examined the anti-metastatic potential of peritumoral
      monotherapy against murine cutaneous B16F10 melanoma with synthetic
      oligodeoxynucleotides (ODN) containing unmethylated CpG motifs. We demonstrated
      that repeated peritumoral injections of CpG ODN significantly reduced skin tumor
      size. Peritumoral CpG ODN-treatment of skin tumors prevented the development of
      pulmonary B16F10 colonies. Adoptive transfer of splenocytes obtained from CpG ODN
      treated mice markedly reduced the number of previously established pulmonary
      colonies in recipient naive mice. T-lymphocyte depletion studies indicated that
      the anti-metastatic effect was dependent on both CD4+ and CD8+ T cells. These
      results suggest that CpG ODN are promising as a preventive and therapeutic anti
      metastatic measure against melanoma.

PMID- 15245442
TI  - Long-term murine keratinocyte cultures become tetraploid, yet maintain the
      ability to stratify.

PMID- 15245443
TI  - Cutaneous body image: empirical validation of a dermatologic construct.

PMID- 15245444
TI  - Serum antibodies against human intracisternal A-type particle (HIAP) endogenous
      retrovirus in Alopecia areata patients: a hallmark of autoimmune disease?

PMID- 15245445
TI  - Vanilloid receptor-1 (VR1) is widely expressed on various epithelial and
      mesenchymal cell types of human skin.

PMID- 15245446
TI  - Genes for freckles.

PMID- 15245452
TI  - Regulating the regulators: routing the Wnt-beta-catenin--Lef signals.

PMID- 15245453
TI  - Human papillomaviruses and the skin: more to be learned.

PMID- 15245455
TI  - How to avoid problems in redo coronary artery bypass surgery.
AB  - The objective of my presentation is to discuss the various intra- and
      perioperative problems related to redo coronary artery bypass surgery so that we
      can minimize complications during surgery and improve the final outcomes. When a
      patient accepts redo cardiac surgery in spite of known higher morbidity and
      mortality, the patient strongly believes that he will come out of this operation
      successfully and enjoy several more years of life. Weintraub reported that redo
      cardiac surgery has higher mortality and morbidity; 5% in elective cases, 11% in
      urgent cases, and 16.4% in emergency cases. He and associates described that the
      female gender, a low ejection fraction (EF), and preoperative arrhythmias are
      significant risk factors. Lemmer and associates described poor postoperative
      functional results with the majority of patients having emergency repeat coronary
      artery revascularization developing recurrent ischemic syndrome within a short
      period of time. I am outlining the problems from our experience of 543 patients
      in the last five years.

PMID- 15245456
TI  - Myocardial protection in reoperative coronary artery bypass grafting:.
AB  - Redo coronary artery bypass grafting (CABG) is associated with higher morbidity
      and mortality when compared to first-time CABG. Myocardial infarction and
      dysfunction contribute significantly to the increased risk of redo CABG. Results
      of reoperative coronary surgery have gradually improved, largely because of
      improvements in myocardial protection techniques. In the present review we will
      highlight the principles of myocardial protection in redo CABG patients with an
      emphasis on retrograde cardioplegia.

PMID- 15245457
TI  - The radial artery in reoperative coronary bypass surgery:.
AB  - BACKGROUND: Failure of saphenous vein grafts (SVG) is a significant cause for
      coronary reoperation (redo CABG). The radial artery (RA) because of its
      availability, and versatility is well suited to use (together with internal
      thoracic arteries (ITA) in redo CABG, especially to replace failed SVG. We
      evaluated our experience where the RA was a major conduit in redo CABG over the
      past 5 years. METHODS: From July 1996 to June 2002, 590 consecutive patients
      underwent redo CABG where one or both RA(s) were used, together with LITA or
      RITA. The mean age was 67.3 years, 82% were male, and 19% diabetic, 419 (71%) had
      Class III or IV angina, 135 (23%) had left main stenosis, and 210 (36%) had an
      LVEF < 0.50. There were a total of 877 RA conduits (303 single, 287 bilateral),
      518 new LITA or RITA. A mean of 2.8 new distal anastomoses constructed 92% (2.6
      per patient)of the arterial grafts. Follow-up was at 1 month, 3 months, and then
      yearly. The results were compared with 6466 primary CABG performed in the same
      time frame, and with a prior cohort of 741 consecutive patients having redo CABG
      without an RA in which identical operative techniques had otherwise been used.
      RESULTS: The 30-day mortality was 3.9% (23 patients). Morbidity was low.
      Perioperative myocardial infarction occurred in 16 (2.7%) patients, stroke in 10
      (1.7%), sternal infection in 10 (1.7%), donor site infection in 2 (0.3%), and
      IABP use in 23 patients (3.9%)-including 10 preoperatively. The results were
      better when compared to a prior cohort of 741 patients with redo CABG (1991 to
      1996) without use of the RA. The results were inferior to that of the
      contemporary primary CABG. Operative mortality was 3.9% versus 0.9%, p = 0.002,
      myocardial infarction 2.7% versus 0.8%, p = 0.03. CONCLUSION: The use of the RA
      (together with ITA) in redo CABG achieved total arterial revascularization in 92%
      of cases and is associated with excellent results, at least equal to or superior
      to those achieved previously.

PMID- 15245458
TI  - Redo mitral valve surgery-a long-term experience.
AB  - BACKGROUND: Our experience with reoperative mitral valve (MV) surgery over a 27
      year period is presented here. METHODS: From January 1975 to June 2002, 11,908
      operations were performed for MV disease. Out of these 744 were reoperations. The
      mean age at primary operation was 23.6 +/- 10.1 years (range 2 to 53 years) and
      at reoperation was 36.0 +/- 11.0 years (range 6 to 65 years) with a mean interval
      of 11.5 +/- 2.5 years. Mitral valve replacement (MVR) was performed following
      previous closed mitral valvotomy (CMV) in 408 patients, open mitral
      commissurotomy (OMC) in 21 patients, and MV repair in 58 patients, MVR in 80
      patients, homograft mitral valve replacement (HMVR) in 11 patients. The reasons
      for reoperation were mainly progression of lesions. Valve thrombosis and
      endocarditis were indications for reoperation following MVR. Twenty-eight
      patients underwent redo CMV, 53 patients underwent OMC, and 14 patients underwent
      MV Repair. RESULTS: Early mortality was 5.64% (n = 42). Hemorrhage and low
      cardiac output were the major causes. Follow-up was 124.8 +/- 30.5 months (2 to
      300 months). Follow-up was 88%. There were no late deaths in the valve repair
      group. There were three episodes of thromboembolism in this group (0.3% per
      patient-year). In the valve replacement group there were six late deaths; three
      due to valve thrombosis, one due to infective endocarditis, and two due to
      anticoagulant-related hemorrhage. There were 13 episodes of thromboembolism in
      this group (0.6% per patient-year). CONCLUSION: Redo MV surgery is safe and can
      be undertaken with acceptable mortality and morbidity.

PMID- 15245459
TI  - Aortic valve replacement in patients with previous cardiac surgery.
AB  - BACKGROUND: Whether minimally diseased aortic valves should be replaced during
      other necessary cardiac operations remains controversial. Part of the decision
      making process in that issue revolves around the risks of subsequent aortic valve
      replacement. This study evaluated the results of aortic valve replacement in
      patients following prior cardiac surgery. METHODS: From February, 1984 through
      December, 2001 first-time aortic valve replacement was performed in 132
      consecutive patients who had previous cardiac surgery utilizing cardiopulmonary
      bypass. Of those patients 89 (67%) had aortic valve replacement at a mean of 8.3
      years after prior coronary artery bypass grafting, and 43 (33%) had aortic valve
      replacement at a mean of 13.0 years after previous procedures other than
      myocardial revascularization. Hospital records of all patients were
      retrospectively reviewed. RESULTS: Early complications included operative
      mortality in six (6.7%) of the patients with prior coronary grafting and no
      mortality in the group with other prior operations. Patients having prior
      coronary grafting had more nonfatal complications than those with other previous
      procedures. CONCLUSIONS: Aortic valve replacement in patients following previous
      cardiac surgery can be accomplished with acceptable mortality and morbidity.
      Routine replacement of aortic valves that are minimally diseased during coronary
      artery bypass grafting may not be warranted.

PMID- 15245460
TI  - Off-pump surgery and alternatives to standard operation in redo coronary surgery.
AB  - BACKGROUND: Reoperative coronary artery bypass grafting (CABG) has been
      associated with higher mortality and morbidity than first-time CABG. Off-pump
      surgery has been introduced in an effort to reduce morbidity associated with
      traditional on-pump CABG. However, these techniques present unique challenges in
      the reoperative setting. A review of our experience was undertaken to determine
      safety, efficacy, and technical challenges in beating heart reoperative CABG.
      METHODS: From January 1999 through April 2003 reoperative CABG procedures
      performed by a single surgeon were treated on an "intention to treat" basis
      without cardiopulmonary bypass. A standardized operative technique employing
      suction stabilization and exposure devices were used for sternotomy procedures
      with stabilization devices employed for limited access single-vessel
      revascularization. RESULTS: Eighty-six of eighty-seven (99%) consecutive patients
      undergoing reoperative CABG had the procedure initiated off-pump. There were 24
      of 62 females/males (28%/72%) with a mean age of 64.3 (34 to 92). Eighty-one of
      eighty-six (94.2%) procedures were successfully completed off-pump. Five (5.8%)
      conversions were due to hemodynamic instability, inability to dissect dense
      adhesions (2), inability to locate an intramyocardial LAD (1). The procedures
      were performed via a median sternotomy in 67 patients (78%) and by limited
      anterior or lateral thoracotomy in 19 patients (22%). The operative mortality was
      2 of 86, predicted risk 6.7%. There was no mortality in the converted patients.
      Postoperative length of stay was 5.5 days. There were no strokes or perioperative
      myocardial infarctions. Complications included reoperation for bleeding in 2.2%.
      Sixty-one of sixty-six (92.4%) patients were able to be extubated in the
      operating room. The rate of transfusion was 23 in 86 patients (26.5%), and atrial
      fibrillation was 5 in 86 patients (5.8%). CONCLUSION: Off-pump CABG can
      technically be performed safely in most patients presenting for reoperative CABG.
      Outcomes appear to be improved compared with published outcomes of reoperative on
      pump CABG surgery.

PMID- 15245461
TI  - Evolution of redo cardiac surgery: review of personal experience.
AB  - This presentation summarizes the author's personal observations on the major
      advances in reoperative cardiac surgery. They include earlier referral for
      cardiac prosthetic and bioprosthetic cardiac valve dysfunction, alternative
      incisional approaches to minimize injury to adherent cardiac structures,
      alternative perfusion sites, improved hemostasis on cardiopulmonary bypass,
      improved myocardial protection, tailoring the valve prosthesis to the patients'
      anatomy and clinical situation, "no-touch" technique in reoperative coronary
      artery surgery, and increasing use of hypothermic circulatory arrest for
      recurrent ascending arch and descending thoracic pathology. Each of these is
      explained in detail with the appropriate references and retrospective data
      collections where appropriate. This risk of reoperative cardiac surgery will
      continue to improve as these and additional techniques continue to evolve and
      become simplified. Further investigation into the clinical uses of minimally
      invasive techniques including robot technology, may eventually reduce morbidity
      and mortality of reoperations to that equal to primary operations.

PMID- 15245462
TI  - Aortic root replacement in patients with previous heart surgery.
AB  - OBJECTIVE: The objective was to review the operative risk and outcomes of redo
      aortic root replacement. PATIENTS AND METHODS: From July 1990 to December 2001,
      aortic root replacement was performed in 165 patients who had at least one
      previous cardiac operation. Their mean age was 49 +/- 16 years and 78% were men.
      Twenty-eight patients had a previous aortic root replacement. The principal
      indication for surgery was prosthetic aortic valve dysfunction. All the patients
      had a dilated, calcified, ruptured, or some other abnormality of the aortic root.
      The follow-up was complete and extended from 0 to 12.5 years, mean of 3.8 years.
      RESULTS: There were 12 operative (7%) and 20 late deaths (12%). The survival at 8
      years was 68%+/- 6%. The principal cause of death was cardiovascular related. Age
      at increments of 5 years (risk ratio: 1.2; CI: 95%; 1.1 to 1.4) and preoperative
      New York Heart Association functional class IV (risk ratio: 2.2; CI: 95%: 1.1 to
      4.7) were the only two independent predictors of death. Two patients had a stroke
      and died; two patients developed three episodes of prosthetic valve endocarditis
      and died. Three patients were reoperated on because of endocarditis in one,
      bioprosthetic valve failure in one, and dehiscence of a prosthetic mitral valve
      in one. The freedom from reoperation at 8 years was 93%+/- 5%. CONCLUSIONS: Redo
      aortic root replacement can be done with low operative mortality in elective
      patients and the risk increases in those who need emergent surgery and are older.
      The long-term results are satisfactory and similar to those for patients who have
      aortic root replacement for the first time.

PMID- 15245464
TI  - Charting the future by examining the past:.

PMID- 15245463
TI  - Operative strategies to reduce complications in Novacor left ventricular assist
      device placement.
AB  - BACKGROUND: The original Novacor left ventricular assist device (LVAD) implant
      procedure has been extensively modified since its introduction. Our goal is to
      describe, in a concise and comprehensive fashion, the status of this evolution as
      we currently employ it at our institution. We will also investigate the possible
      impact of the adoption of this current methodology on the incidence of
      perioperative hemorrhage at our institution. METHODS: The number of units of
      blood transfused on the day of implant surgery and the incidence of reexploration
      for postoperative hemorrhage were compared between the early group of consecutive
      patients implanted before adoption of the described implant strategy (n = 10) and
      the late group of consecutive patients implanted after uniform implementation of
      this methodology (n = 20). RESULTS: Operative and immediate postoperative
      hemorrhage, as demonstrated by the number of blood transfusions on the day of
      implant surgery, was significantly reduced in the group of consecutive patients
      implanted after adoption of these techniques when compared to the group of
      patients implanted prior to technical modification. CONCLUSION: The currently
      utilized Novacor LVAD implant procedure is described in detail. The amount of
      blood transfused on the implant day has significantly decreased since the uniform
      adoption of the current procedure, suggesting that the degree of perioperative
      hemorrhage has been favorably affected. Although implantation complications can
      be surgeon, device, institution and patient-specific, the strategies employed in
      the current implant procedure may be helpful at other heart failure centers.

PMID- 15245465
TI  - Minimized mortality and neurological complications in surgery for chronic arch
      aneurysm: axillary artery cannulation, selective cerebral perfusion, and
      replacement of the ascending and total arch aorta.
AB  - OBJECTIVE: Cerebral complication is still a major concern in surgery for
      arteriosclerotic aortic arch disease. For preventing this complication, axillary
      artery cannulation, selective cerebral perfusion, and replacement of the
      ascending and arch aorta were applied to thoracic aortic aneurysm involving
      aortic arch. METHOD: From May 1999 to July 2002, consecutive 39 patients with
      true aneurysm (29 patients) or chronic aortic dissection (10 patients) involving
      aortic arch underwent replacement of the ascending and arch aorta with an
      elephant trunk under hypothermic cardiopulmonary bypass through the axillary
      artery cannulation and selective cerebral perfusion. The brain was continuously
      perfused without any intermission through the axillary artery. Concomitant
      operation included coronary artery bypass grafting (CABG) in two patients, aortic
      valve replacement (AVR) in one, Bentall operation in two, mitral valve
      replacement (MVR) in one, and aortic valve sparing operation in one. Patient age
      at operation was 40-84 (72 + 9) years and 24 of them were older than 70 years of
      age. RESULTS: There was one operative death (2.5%) due to bleeding from the left
      lung, and one hospital death due to respiratory failure. Postoperative permanent
      neurological dysfunction was found in one patient (2.5%). Two patients presented
      temporary neurological dysfunction (5%). Thirty-six of the 39 patients were
      discharged from hospital on foot. CONCLUSION: Continuous perfusion through the
      axillary artery with selective cerebral perfusion and replacement of the
      ascending and arch aorta may minimize cerebral complication leading to
      satisfactory results in patients with chronic aortic aneurysm involving aortic
      arch.

PMID- 15245466
TI  - Compression of mediastinal structures treated by extra-anatomic bypass grafting.
AB  - Extra-anatomic bypass grafts have been used to treat complex and recurrent forms
      of coarctation of the aorta. Here we describe the use of an extra-anatomic bypass
      graft from the ascending to supraceliac aorta to treat an unusual complication of
      compression of mediastinal structures caused by a bucket handle graft.

PMID- 15245467
TI  - Internal thoracic artery blood flow is not affected by major side branch.
AB  - We report a case of a 73-year-old man in which coronary angiography demonstrated
      a large side branch of the internal thoracic artery (ITA). The side branch was
      identified intraoperatively. As assessed intraoperatively by transit time Doppler
      flow measurement, temporary occlusion of the side branch showed no effect on ITA
      flow, which remained unchanged at 49 mL/min after anastomosis to left anterior
      descending coronary artery.

PMID- 15245468
TI  - Papillary fibroelastoma of the interatrial septum: a case report.
AB  - Primary cardiac tumors are rare, with benign lesions outnumbering malignant ones
      by a margin of over four to one. Amongst the benign cardiac neoplasms, papillary
      fibroelastomas are reported second only to myxomas. Papillary fibroelastomas
      commonly rise from heart valves and their size ranges from a few millimeters to
      well over 2.0 cm in diameter. While myxomas commonly arise from the interatrial
      septum, we present the rare example of a large papillary fibroelastoma arising
      from the left side of the interatrial septum.

PMID- 15245469
TI  - Operative management of atherosclerotic aortic aneurysm in a patient with
      bicuspid aortic valve disease.
AB  - An adult patient with a congenital bicuspid aortic valve, an aneurysm, and a
      calcific atherosclerotic plaque of the ascending aorta, underwent an aortic valve
      replacement, a vertical reduction aortoplasty, an endarterectomy, and a distal
      external synthetic wrapping.

PMID- 15245470
TI  - Ruptured giant syphilitic aneurysm of the descending aorta in an octogenarian.
AB  - Syphilis can lead to saccular aneurysms of the thoracic aorta. Today syphilitic
      aortic aneurysms are rare. The average time from primary infections to the
      development of aortic aneurysms is 10 to 15 years. An 83-year-old man was
      admitted with a giant aneurysm of the descending thoracic aorta. The patient had
      first experienced subacute pain in the left hemithorax some weeks previously.
      Computer tomography scan detected an 11 x 11 cm aneurysm of the descending aorta.
      Serodiagnostic tests for syphilis were highly positive. Femoro-femoral bypass was
      initiated and a tube graft was interposed. The postoperative course was
      uneventful, the patient was discharged at the twentieth postoperative day.
      Histological examination of the aneurysmal wall showed typical syphilitic
      changes. Postoperatively, Penicillin G was given for 6 months. Three years later
      the patient remains asymptomatic. Although extremely rare today, tertiary
      syphilis should be considered in the differential diagnosis of thoracic
      aneurysms. In selected octogenarians replacement of the descending aorta is
      possible.

PMID- 15245471
TI  - Cardiac hydatid cysts: surgical treatment and results.
AB  - From 1991 to 2000 six patients with intracardiac echinococcosis underwent
      surgical treatment. Four patients were females and two were males, age of the
      patients ranged from 20 to 68 years. Two patients had symptoms, all patients were
      diagnosed as a component of multi-organ echinococcosis and three of them
      underwent operation before. They were examined serologically and
      echocardiographically. Cardiac hydatidosis were diagnosed in right ventricle (in
      three cases), left ventricle (in one case), and interventricular septum (in two
      cases). Sternotomy was the approach used and all patients were operated on using
      cardiopulmonary bypass. Intraoperative rupture did not occur. There was no
      operative mortality, the only morbidity was complete atrioventricular block
      necessitating VVD pacemaker implantation in the patient with hydatid cyst
      involving the basal interventricular septum. All patients were followed by
      medical treatment with albendazole (400 mg/day) and no recurrences were reported
      in the late follow-up.

PMID- 15245472
TI  - Changing trends in mechanical circulatory assistance:.
AB  - BACKGROUND: The success of long-term implantable ventricular assist devices has
      led to their increased use in patients previously thought to be unsuitable for
      mechanical support. As a result, the demographic profile of patients presenting
      for LVAD support has changed over time. We reviewed our institutional experience
      to identify emerging risk factors and changing trends in patients who received
      the HeartMate VE LVAD. METHODS: The clinical records were reviewed of 131
      consecutive LVAD recipients between 1996 and 2001. All perioperative data were
      collected prospectively and entered into an institutional database. All patients
      received a preoperative risk stratification score based upon published criteria.
      The cohort was arbitrarily divided into early (n = 45), mid (n = 45), and late
      groups (n = 41). RESULTS: Overall operative mortality was 25% with no difference
      between groups. The mean risk score increased significantly over time (early 3.5
      +/- 0.4 vs. late 5.3 +/- 0.3, p < 0.05). The proportion of patients at high risk
      for mortality (score >5) was significantly higher in the late group (51% vs. 29%,
      p < 0.05). Although ventilation time and ICU stay was similar for all groups,
      hospital stay was longer in the late group (43 days vs. 23 days, p < 0.05). Mean
      duration of support fell from 90 to 59 days, but this failed to achieve
      statistical significance. Out-patient therapy decreased from 73% in the early
      group to 15% in the late group (p < 0.001). Multivariate analysis identified
      right heart failure (odds ratio 4.1, 95% CI 2-11) and risk score (OR 1.4, 95% CI
      1.2-1.6) as independent predictors of death. CONCLUSIONS: Despite an increasingly
      high risk patient population, the mortality associated with LVAD therapy has
      remained constant. Duration of LVAD support has decreased with a trend toward
      transplantation before hospital discharge. These data continue to support the
      aggressive institution of mechanical assistance for acute or chronic heart
      failure.

PMID- 15245473
TI  - John W. Kirklin: reminiscences of a surgical resident.

PMID- 15245474
TI  - Auxiliary subunit regulation of high-voltage activated calcium channels expressed
      in mammalian cells.
AB  - The effects of auxiliary calcium channel subunits on the expression and
      functional properties of high-voltage activated (HVA) calcium channels have been
      studied extensively in the Xenopus oocyte expression system, but are less
      completely characterized in a mammalian cellular environment. Here, we provide
      the first systematic analysis of the effects of calcium channel beta and alpha(2)
      delta subunits on expression levels and biophysical properties of three different
      types (Ca(v)1.2, Ca(v)2.1 and Ca(v)2.3) of HVA calcium channels expressed in tsA
      201 cells. Our data show that Ca(v)1.2 and Ca(v)2.3 channels yield significant
      barium current in the absence of any auxiliary subunits. Although calcium channel
      beta subunits were in principle capable of increasing whole cell conductance,
      this effect was dependent on the type of calcium channel alpha(1) subunit, and
      beta(3) subunits altogether failed to enhance current amplitude irrespective of
      channel subtype. Moreover, the alpha(2)-delta subunit alone is capable of
      increasing current amplitude of each channel type examined, and at least for
      members of the Ca(v)2 channel family, appears to act synergistically with beta
      subunits. In general agreement with previous studies, channel activation and
      inactivation gating was regulated both by beta and by alpha(2)-delta subunits.
      However, whereas pronounced regulation of inactivation characteristics was seen
      with the majority of the auxiliary subunits, effects on voltage dependence of
      activation were only small (< 5 mV). Overall, through a systematic approach, we
      have elucidated a previously underestimated role of the alpha(2)-delta(1) subunit
      with regard to current enhancement and kinetics. Moreover, the effects of each
      auxiliary subunit on whole cell conductance and channel gating appear to be
      specifically tailored to subsets of calcium channel subtypes.

PMID- 15245475
TI  - Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS
      SOD1 mice.
AB  - We have investigated the expression of Hsp25, a heat shock protein constitutively
      expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that
      express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting
      showed that a decrease of Hsp25 protein expression occurred in motoneurons of
      G93A mice prior to the onset of motoneuron death and muscle weakness. This
      decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as
      identified by cellulose acetate filtration and Western blot analysis. In contrast
      to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT
      PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels
      occurs post-transcriptionally. In view of the cytoprotective properties of Hsp25
      and the temporal relationship between decreased Hsp25 expression and the onset of
      motoneuron death, it is feasible that reduced Hsp25 concentration contributes to
      the degeneration of motoneurons in G93A mice. These data are consistent with the
      idea that mutant SOD1 may reduce the availability of the protein quality control
      machinery in motoneurons.

PMID- 15245476
TI  - Developmental up-regulation of MnSOD in rat oligodendrocytes confers protection
      against oxidative injury.
AB  - Periventricular leukomalacia, the predominant pathological lesion underlying
      cerebral palsy in premature infants, is thought to be the result of hypoxic
      ischemic injury to the cerebral white matter. The main cell type injured is the
      developing oligodendrocyte (OL), which has been shown to be more sensitive than
      mature OLs to both excitotoxic and oxidative mechanisms of injury. A maturation
      dependence of OL vulnerability to cystine deprivation-induced glutathione
      depletion has been previously demonstrated in culture. We hypothesized that
      mitochondria could be involved in this toxicity by generating superoxide and that
      increased superoxide dismutase (SOD) activity in mature OLs may account for their
      greater resistance. Cystine deprivation toxicity was found to be associated with
      mitochondrial dysfunction and intracellular superoxide accumulation in developing
      OLs. CuZnSOD protein expression and enzyme activity was similar along the OL
      lineage. In contrast, MnSOD was up-regulated in mature OLs, as manifested by a
      53% increase in its expression and a four-fold increase in its activity.
      Overexpressing MnSOD in developing OLs was associated with a protective effect on
      mitochondrial membrane potential and a decrease in cell death induced by mild
      cystine deprivation. The greater challenge presented by total cystine deprivation
      was resistant to MnSOD overexpression and appeared to be related to hydrogen
      peroxide toxicity. These data suggest a primary involvement of superoxide in
      glutathione depletion toxicity in developing OLs, and suggest an important role
      for MnSOD in the resistance observed in mature OLs.

PMID- 15245477
TI  - Apical endocytosis in outer hair cells of the mammalian cochlea.
AB  - Outer hair cells (OHCs), the sensory-motor cells of the mammalian cochlea,
      contain an endocytic tubulovesicular compartment below their apical stereocilia.
      We have used two-photon imaging of FM1-43 in the intact epithelium to show that
      these cells take up membrane in a Ca(2+)-dependent manner from a distinct apical
      site. The uptake rate was 0.8 microm(2)/s and internalized membrane was
      trafficked rapidly to a compartment along the lateral wall and distinct
      intracellular compartments. Double labelling with FM1-43 and DiOC(6), an
      endoplasmic reticulum (ER) marker, showed that these compartments are part of the
      tubulovesicular endoplasmic reticulum of OHCs. Labelling with a lysosomal marker
      showed that OHC lysosomes are restricted to the apex. Using the protein marker
      wheat germ agglutinin (WGA-FITC) we demonstrate that apical protein
      internalization and trafficking is about eight times slower than membrane
      internalization. Using double labelling with FM1-43 and WGA-FITC, we show that
      membrane and protein internalization are apically colocalized but that patterns
      of protein and membrane traffic differ. Protein was targeted only to the most
      apical third of the lateral wall. In control conditions, OHCs displayed only weak
      WGA-FITC surface labelling at the site of endocytosis. Lowering the rate of
      apical endocytosis increased this surface signal. The results suggest that OHCs
      endocytose membrane and membrane proteins with a high turnover rate and that
      these cells may use apical endocytosis to sort proteins via an indirect pathway
      to the lateral membrane.

PMID- 15245478
TI  - Brain hyperthermia induced by MDMA (ecstasy): modulation by environmental
      conditions.
AB  - Drugs of abuse, such as 3,4-methylenedioxymethamphetamine (MDMA), often have more
      powerful effects during states of increased activation and under specific
      environmental conditions. Because hyperthermia is a major complication of MDMA
      use and a factor potentiating neurotoxicity, we examined the effects of this drug
      (9 mg/kg, sc; approximately one-fifth of the known LD(50) in rats) on brain
      [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus
      temporalis) temperatures in male rats under conditions that either model human
      drug use (social interaction with female, warm temperature) or restrict heat
      dissipation from the brain (chronic occlusion of jugular veins). Under quiet
      resting conditions at 23 degrees C, MDMA induced a moderate but prolonged
      hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature
      increases than muscle, suggesting metabolic neural activation as a primary cause
      of brain hyperthermia. During social interaction with a female, brain
      hyperthermia induced by MDMA was significantly potentiated (+89%). Brain
      hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals
      with chronically occluded jugular veins, suggesting impaired cerebral outflow
      enhances intrabrain heat accumulation. At 29 degrees C, MDMA pushed temperatures
      in the brain to its biological limits (>41 degrees C; +268%), resulting in
      fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain
      activation and restricting heat dissipation, MDMA use under 'party' conditions
      may be much more dangerous than under standard laboratory conditions.

PMID- 15245479
TI  - Dendritic excitability and localization of GABA-mediated inhibition in spider
      mechanoreceptor neurons.
AB  - GABAergic inhibition of mechanosensory afferent axon terminals is a widespread
      phenomenon in vertebrates and invertebrates. Spider mechanoreceptor neurons
      receive efferent innervation on their peripherally located axons, somata and
      sensory dendrites, and the dendrites have recently been shown to be excitable.
      Excitability of the spider sensory neurons is inhibited by muscimol and GABA,
      agonists of ionotropic GABA receptors. Here we asked where in the neurons this
      inhibition occurs. We found no evidence for inhibition of action potentials in
      the sensory dendrites, but axonal action potentials were rapidly suppressed by
      both agonists. Earlier work showed that metabotropic GABA(B) receptors are
      located on the dendrites and distal somata of the spider sensory neurons, where
      they modulate voltage-activated conductances and may provide slower, prolonged
      inhibition. Therefore, GABA released from single peripheral efferents may
      activate both ionotropic and metabotropic receptor types, providing rapid
      suppression of axonal activity followed by slower inhibition that eventually
      prevents action potential initiation in the distal dendrites.

PMID- 15245480
TI  - Synchronization of oxytocin neurons in suckled rats: possible role of bilateral
      innervation of hypothalamic supraoptic nuclei by single medullary neurons.
AB  - We have previously shown that oxytocin neurons located in the four hypothalamic
      magnocellular nuclei display synchronous bursts of action potentials before each
      milk ejection. The mechanisms involved in such a synchronization have, however,
      not yet been elucidated. In this study, we test the hypothesis of an extranuclear
      synchronization arising from a common extrahypothalamic input innervating
      bilateral magnocellular nuclei. First, two different retrograde tracers were
      injected into the right and left supraoptic nuclei of rats that were fixed 5-7
      days later. Each tracer labelled numerous neurons in various brain regions
      ipsilateral or contralateral to the injection site, but colocalization of the two
      tracers within the same cell body could only be detected bilaterally in neurons
      in the ventromedial regions of the medulla oblongata. The axonal projections of
      these medullary neurons were then visualized by the unilateral microinjection of
      an anterograde tracer (BDA) within the ventromedial medulla oblongata. BDA
      labelled axons afferent to the hypothalamus were found to branch towards both
      supraoptic nuclei through medial portions of the optic chiasma. Finally, in
      anaesthetized lactating rats, surgical lesions were placed medially through the
      optic chiasma and the electrical activity of oxytocin neurons in bilateral
      supraoptic nuclei was pair-recorded during suckling. The incidence of synchronous
      bursts in oxytocin neurons located within bilateral supraoptic nuclei were
      dramatically altered only when the medial portions of the optic chiasma were
      totally lesioned. Taken together, these data suggest that medullary neurons
      afferent to bilateral supraoptic nuclei are involved in the recruitment and
      synchronization of bursting in oxytocin neurons during suckling.

PMID- 15245481
TI  - Distribution of HCN1 and HCN2 in rat auditory brainstem nuclei.
AB  - Auditory brainstem neurons that are involved in the precise analysis of the
      temporal pattern of sounds have ionic currents activated near the resting
      potential to shorten membrane time constants. One of these currents is the
      hyperpolarization-activated current (Ih). Molecular cloning of the channels
      underlying Ih revealed four different isoforms (HCN1-4). HCN1 and HCN2, which are
      widely distributed in the brain, differ in their activation kinetics, voltage
      dependence and sensitivity to cAMP. We determined the distribution of the HCN1
      and HCN2 isoform in the auditory brainstem and midbrain of young rats (P20-30),
      using standard immunohistochemical techniques. HCN1 antibodies gave rise to
      punctate staining on the somatic and dendritic membrane. Strong HCN1 staining was
      present on octopus and bushy cells of the ventral cochlear nucleus, principal
      neurons of the lateral and medial superior olive, and neurons of the ventral
      nucleus of the lateral lemniscus. No HCN1 staining was observed in the dorsal
      cochlear nucleus and the medial nucleus of the trapezoid body (MNTB). In
      contrast, HCN2 staining was strongest in the MNTB and the dorsal nucleus of the
      lateral lemniscus. Strong HCN2 antibody labelling was also observed in bushy
      cells of the ventral cochlear nucleus. In the central nucleus of the inferior
      colliculus only a subpopulation of neurons showed HCN1 or HCN2 immunolabelling.
      This differential distribution of HCN1 and HCN2 channels is in agreement with the
      physiologically observed Ih currents in corresponding neuronal populations and
      might represent the basis for functional heterogeneity and diverse sensitivity to
      neuromodulators.

PMID- 15245482
TI  - Sympathetic activation triggers endogenous opioid release and analgesia within
      peripheral inflamed tissue.
AB  - Stress induces analgesia by mechanisms within and outside the brain. Here we show
      that the sympathetic nervous system is an essential trigger of intrinsic opioid
      analgesia within peripheral injured tissue. Noradrenaline, injected directly into
      inflamed hind paws of male Wistar rats, produced dose-dependent antinociception,
      reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)-
      and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing
      immune cells and noradrenaline induced adrenergic receptor-specific release of
      beta-endorphin from immune cell suspensions. This antinociceptive effect of
      noradrenaline was reversed by micro - and delta-opioid antagonists as well as by
      anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by
      chemical sympathectomy and by adrenergic antagonists. These findings indicate
      that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on
      inflammatory cells to release beta-endorphin, which induces analgesia via
      activation of peripheral opioid receptors.

PMID- 15245483
TI  - Input- and subunit-specific AMPA receptor trafficking underlying long-term
      potentiation at hippocampal CA3 synapses.
AB  - Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres
      (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these
      synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR)
      dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for
      induction of MF LTP and AF LTP, respectively. This implies that molecular and
      functional properties differ between MF and AF synapses at both presynaptic and
      postsynaptic sites. In this study, we focused on the difference in the
      postsynaptic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptors (AMPARs) between these synapses. To trace the subunit-specific
      trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced
      into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis
      viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced
      by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were
      inserted into both MF and AF postsynaptic sites in a neuronal activity
      independent manner. Endogenous Ca(2+)-impermeable AMPARs at these synapses were
      replaced with exogenous Ca(2+)-permeable receptors, and Ca(2+) influx via the
      newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses.
      In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively
      incorporated into AF postsynaptic sites, and only a small amount into MF
      postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the
      activity of Ca(2+)/calmodulin-dependent kinase II or high-frequency stimulation
      to induce LTP at AF synapses, but not at MF synapses. These results indicate that
      MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in
      CA3 pyramidal neurons.

PMID- 15245484
TI  - Experimental evidence and modeling studies support a synchronizing role for
      electrical coupling in the cat thalamic reticular neurons in vivo.
AB  - Thalamic reticular (RE) neurons are crucially implicated in brain rhythms. Here,
      we report that RE neurons of adult cats, recorded and stained intracellularly in
      vivo, displayed spontaneously occurring spikelets, which are characteristic of
      central neurons that are coupled electrotonically via gap junctions. Spikelets
      occurred spontaneously during spindles, an oscillation in which RE neurons play a
      leading role, as well as during interspindle lulls. They were significantly
      different from excitatory postsynaptic potentials and also distinct from fast
      prepotentials that are presumably dendritic spikes generated synaptically.
      Spikelets were strongly reduced by halothane, a blocker of gap junctions. Multi
      site extracellular recordings performed before, during and after administration
      of halothane demonstrated a role for electrical coupling in the synchronization
      of spindling activity within the RE nucleus. Finally, computational models of RE
      neurons predicted that gap junctions between these neurons could mediate the
      spread of low-frequency activity at great distances. These experimental and
      modeling data suggest that electrotonic coupling within the RE nucleus plays an
      important role in the generation and synchronization of low-frequency (spindling)
      activities in the thalamus.

PMID- 15245485
TI  - Phenotypic expression of the targeted null-mutation in the dopamine transporter
      gene varies as a function of the genetic background.
AB  - The dopamine transporter (DAT) plays a critical role in calibrating the duration
      and intensity of dopamine (DA) neurotransmission. Mice in which the DAT gene has
      been genetically deleted exhibit constitutively high levels of extrasynaptic DA
      and spontaneous hyperactivity. Numerous studies have characterized the adaptive
      molecular, physiological, and behavioural consequences of abnormal DA
      neurotransmission in these mice. In order to determine the genetic background
      contribution to these phenotypes, the DAT mutation was transferred on C57BL/6JOrl
      (B6) or DBA/2JOrl (D2) inbred backgrounds for more than ten generations of back
      crossing to derive three B6-, D2-, and B6xD2(F(1))-DAT strains. We observed that
      the genetic background dramatically affects phenotypes previously reported on DAT
      knockout (KO) mice. Depending on the genetic background, it was possible to
      restore survival, growth rate and ability to lactate. Interactions with the
      genetic background were found to modulate both quantitative and qualitative
      patterns of novelty-driven spontaneous hyperactivity. The paradoxical calming
      effect of cocaine was observed for all DAT-KO mice. However, the genetic
      background influenced individual threshold responses to both locomotor and
      rewarding effects of cocaine. These findings reveal the extent of phenotypic
      variation associated with the DAT mutation. They also provide concrete arguments
      against the assumption that the normal function of a gene can be inferred
      directly from its mutant phenotype.

PMID- 15245486
TI  - Induction of pseudo-periodic oscillation in voltage-gated sodium channel
      properties is dependent on the duration of prolonged depolarization.
AB  - The neuronal voltage-gated sodium channels play a vital role in the action
      potential waveform shaping and propagation. Here, we report the effects of
      prolonged depolarization (1-160 s) on the detailed kinetics of activation, fast
      inactivation and recovery from slow inactivation in the rNa(v)1.2a voltage-gated
      sodium channel alpha-subunit expressed in Chinese hamster ovary (CHO) cells.
      Wavelet analysis revealed that the duration and amplitude of a prolonged
      sustained depolarization altered all the steady state and kinetic parameters of
      the channel in a pseudo-oscillatory fashion with time-variable period and
      amplitude, often superimposed on a linear trend. The half steady state activation
      potential showed a reversible depolarizing shift of 5-10 mV with duration of
      prolonged depolarization, while half steady state inactivation potential showed a
      hyperpolarizing shift of 43-55 mV. The time periods for most of the parameters
      relating to activation and fast and slow inactivation, lie close to 28-30 s,
      suggesting coupling of these kinetic processes through an oscillatory mechanism.
      Co-expression of the beta1-subunit affected the time periods of oscillation
      (close to 22 s for alpha + beta1) in steady state activation parameters.
      Application of a pulse protocol that mimicked paroxysmal depolarizing shift
      (PDS), a kind of depolarization seen in epileptic discharges, instead of a
      sustained depolarization, also caused oscillatory behaviour in the rNav1.2a alpha
      subunit. This inherent pseudo-oscillatory mechanism may regulate excitability of
      the neurons, account for the epileptic discharges and subthreshold membrane
      potential oscillation and offer a molecular memory mechanism intrinsic to the
      neurons, independent of synaptic plasticity.

PMID- 15245487
TI  - Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine
      kinases uCK-Mi and CK-B suggest a novel neuron-glial relationship for brain
      energy homeostasis.
AB  - The creatine/phosphocreatine shuttle system, as catalysed reversibly by creatine
      kinases, is thought to be essential for the storing and buffering of high
      phosphate-bound energy in tissues with high energy demand. In the present study,
      we aimed to clarify the cellular system of creatine biosynthesis and its energy
      metabolism in the mouse brain by immunohistochemistry for creatine biosynthetic
      enzyme S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT),
      ubiquitous mitochondrial creatine kinase (uCK-Mi) and brain-type cytoplasmic
      creatine kinase (CK-B). GAMT was expressed highly in oligodendrocytes and
      olfactory ensheathing glia and moderately in astrocytes, whereas GAMT was very
      low in neurons and microglia. By contrast, uCK-Mi was expressed selectively in
      neurons and localized in their mitochondria in dendrites, cell bodies, axons and
      terminals. The distinct and almost complementary distribution of GAMT and uCK-Mi
      suggests that the creatine in neuronal mitochondria is derived not only from the
      circulation, but also from local glial cells associated with these neuronal
      elements. By contrast, CK-B was selective to astrocytes among glial populations,
      and was exclusive to inhibitory neurons among neuronal populations.
      Interestingly, these cells with high CK-B immunoreactivity are known to be highly
      resistant to acute energy loss, such as hypoxia and hypoglycemia. Considering
      that phosphocreatine generates ATP much faster than the processes of glycolysis
      and oxidative phosphorylation, the highly regulated cellular expressions of
      creatine biosynthetic and metabolic enzymes suggest that the
      creatine/phosphocreatine shuttle system plays a role in brain energy homeostasis
      through a novel neuron-glial relationship.

PMID- 15245488
TI  - Both d- and l-glutamate induce transporter-mediated presynaptic autoinhibition of
      transmitter release.
AB  - In crayfish motor nerve terminals l-glutamate (Glu) is the excitatory transmitter
      and low l-Glu concentrations exert autoinhibition by inhibiting release of Glu
      quanta from the terminals. This autoinhibition has been shown to be mediated by
      binding and transport of l-Glu by Glu transporters in the presynaptic membrane.
      Activated transporters open an associated Cl(-) channel and inhibit release [J.
      Dudel & M. Schramm (2003) Eur. J. Neurosci., 18, 902-910]. The excitatory,
      glutamatergic synaptic transmission is specific for the l-Glu isomer. However,
      transporters are non-selective for the stereoisomers. It is shown here that low
      concentrations (5 micro m) of d- as well as l-Glu inhibit quantal release on
      average to 55 and 68%, respectively. The power of inhibition varies widely at
      different terminals but the local sensitivity to d-Glu is seen to be the same as
      that for l-Glu. l-Glutamate has been reported to reduce the mean amplitude of
      nerve terminal action currents (excitatory nerve terminal currents) by about 10%,
      presumably due to the opening of Cl(-) channels. Evidence is given that d-Glu
      also inhibits this by an average of 10% (P < 0.001), as expected if both l- and d
      Glu activate a transporter-associated Cl(-) conductance. The results give further
      support for this novel mechanism of regulation of synaptic strength.

PMID- 15245489
TI  - Regulation of photoreceptor Per1 and Per2 by light, dopamine and a circadian
      clock.
AB  - In the Xenopus laevis retina, a principal model for retinal circadian
      organization, photoreceptors have all the properties of circadian oscillators.
      However, rhythmic oscillations of Per1 gene expression in the inner retina (but
      not photoreceptors) have been reported in mice with the suggestion that mice and
      frogs have a different retinal circadian organization. Although it is known that
      two period genes (xPer1 and xPer2) exhibit different temporal patterns of
      expression in the Xenopus retina, and that one (xPer2) is directly responsive to
      light and dopamine, it is not known whether this reflects the properties of
      period genes within photoreceptor oscillators or among distinct retinal cell
      populations. We addressed this by determining the cellular site of light and
      dopamine regulated xPer2 expression, and the diurnal expression of both xPer1 and
      xPer2 using in situ hybridization. Our data show that both xPer1 and xPer2 are
      expressed in most cell types in the retina, including inner nuclear neurons and
      ganglion cells. However, light and quinpirole, a dopamine agonist, increase xPer2
      levels specifically in photoreceptors, and the effect of quinpirole, but not
      light, is blocked by pCPT-cAMP. Furthermore, antiphasic diurnal expression of
      xPer1 and xPer2 also occurs in photoreceptors. Our analysis does not provide
      insight into the near constitutive expression of period genes in the inner
      retina, but supports a model in which light- and dopamine regulated-xPer2 and
      rhythmic xPer1 play critical roles in entrainment and circadian oscillations
      within photoreceptors.

PMID- 15245490
TI  - TRPV1 and CB(1) receptor-mediated effects of the endovanilloid/endocannabinoid N
      arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal
      responses in the rat.
AB  - N-arachidonoyl-dopamine (NADA) is an endogenous ligand at TRPV1 and CB(1)
      receptors, which are expressed on primary afferent nociceptors. The aim of this
      study was to determine contributions of proposed pronociceptive TRPV1 and
      antinociceptive CB(1) receptors to effects of peripheral NADA on primary afferent
      fibre function. Effects of NADA on primary afferent nociceptor function,
      determined by whole cell patch clamp and calcium imaging studies of adult dorsal
      root ganglion (DRG) neurons, were determined. Application of NADA (1 microm) to
      DRG neurons depolarized the resting membrane potential (Vm) from -58 +/- 1 to -44
      +/- 3 mV (P < 0.00001) and evoked a significant increase (P < 0.0001) in
      intracellular calcium (74 +/- 11% of response to 60 mm KCl), compared to basal.
      The TRPV1 receptor antagonist capsazepine abolished NADA-evoked depolarization of
      Vm (P < 0.0001) and NADA-evoked calcium responses (P < 0.001), which were also
      blocked by the CB(1) receptor antagonist SR141716A (P < 0.001). Effects of NADA
      (1.5 microg and 5 microg/50 microL) on mechanically evoked responses of dorsal
      horn neurons in anaesthetized Sprague-Dawley rats were studied. Intraplantar
      injection of the higher dose of NADA (5 microg/50 microL) studied significantly
      inhibited innocuous (8, 10 g) mechanically evoked responses of dorsal horn
      neurons compared to vehicle, effects blocked by intraplantar injection of
      SR141716A. Higher weight (26-100 g) noxious-evoked responses of dorsal horn
      neurons were also significantly inhibited by NADA (5 microg/50 microL), effects
      blocked by intraplantar injection of the TRPV1 antagonist, iodo-resiniferatoxin.
      NADA has a complex pattern of effects on DRG neurons and primary afferent fibres,
      which is likely to reflect its dual site of action at TRPV1 and CB(1) receptors
      and the differential expression of these receptors by primary afferent fibres.

PMID- 15245491
TI  - Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling
      rat strains during massed amygdala kindling: a microdialysis study.
AB  - We investigated the neurochemistry of epileptic seizures in rats selectively bred
      to be seizure-prone (Fast) vs. seizure-resistant (Slow) to amygdala kindling.
      Microdialysis was used to measure levels of amino acids [glutamate, aspartate and
      gamma-aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and
      serotonin) during 'massed' stimulation (MS) (every 6 min) of the ipsilateral
      amygdala for a total of 40 stimulation trials. Behavioral seizure profiles
      together with their afterdischarge thresholds (ADTs) and associated durations
      were assessed during the procedure, and subsequently were redetermined 1, 7 and
      14 days later. Then normal 'daily' kindling commenced and continued until the
      animal reached the fully kindled state. During MS, several generalized seizures
      were triggered in Fast rats that were associated with long afterdischarge (AD)
      durations and intermittent periods of elevated thresholds, but in Slow rats, most
      stimulations were associated with stable ADTs and short ADs. Progressively
      increasing extracellular glutamate and decreasing GABA was observed in Fast rats
      during the MS, whereas Slow rats showed levels similar to baseline values. Levels
      of noradrenaline and dopamine, but not of serotonin, were also increased in both
      strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD
      durations occurred 7 and 14 days following MS, as well as subsequent strong
      positive transfer to daily kindling, all of which were not seen in Slow rats.
      Together, these results show that repeated, closely spaced stimulations of the
      amygdala can differentially alter excitatory and/or inhibitory transmitter levels
      in a seizure network, and that sensitivity to this manipulation is genetically
      determined.

PMID- 15245492
TI  - Increased expression of Nogo-A in hippocampal neurons of patients with temporal
      lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and
      biochemical changes in the hippocampal formation including extensive
      neurodegeneration, reorganization of mossy fibres and sprouting of interneurons.
      Although the anatomical features and some of the physiological consequences of
      hippocampal remodeling have been well documented, the molecular mechanisms
      underlying the profound and orientated outgrowth of hippocampal neurons in TLE
      are not yet understood. The reticulon protein Nogo-A has been associated with an
      inhibitory action on axon growth and plasticity. Using immunohistochemistry and
      in situ hybridization, we investigated the expression of Nogo-A in specimens
      obtained at surgery from patients with TLE compared with those obtained from
      autopsy controls. In control specimens, Nogo-A immunoreactivity and mRNA were
      mainly confined to oligodendrocytes. Only approximately 40% of the specimens
      revealed low expression of Nogo-A mRNA in neurons. In contrast, in TLE patients
      with and without Ammon's horn sclerosis, Nogo-A mRNA and immunoreactivity were
      markedly up-regulated in most neurons (3.6- and 4.4-fold increases in Nogo-A mRNA
      in granule cells of sclerotic and nonsclerotic specimens) and their processes
      throughout the hippocampal formation. Similar elevations in Nogo-A mRNA and
      protein levels were determined by quantitative RT-PCR and Western blotting. Since
      Nogo-A expression was also up-regulated in specimens without hippocampal
      sclerosis, it may be induced by seizures prior to progressing neurodegeneration.

PMID- 15245493
TI  - Interleukin-1beta modulates state-dependent discharge activity of preoptic area
      and basal forebrain neurons: role in sleep regulation.
AB  - Interleukin-1beta (IL-1) is a pro-inflammatory cytokine that has been implicated
      in the regulation of nonrapid eye movement (nonREM) sleep. IL-1, IL-1 receptors
      and the IL-1 receptor antagonist (ra) are present normally in discrete brain
      regions, including the preoptic area (POA) of the hypothalamus and the adjoining
      magnocellular basal forebrain (BF). The POA/BF have been implicated in the
      regulation of sleep-wakefulness. We hypothesized that IL-1 promotes nonREM sleep,
      in part by altering the state-dependent discharge activity of POA/BF neurons. We
      recorded the sleep-wake discharge profiles of 83 neurons in the lateral POA/BF
      and assessed the effects of IL-1, IL-1ra, and IL-ra + IL-1 delivered through a
      microdialysis probe on state-dependent neuronal discharge activity. IL-1
      decreased the discharge rate of POA/BF neurons as a group (n = 55) but wake
      related and sleep-related neurons responded differently. IL-1 significantly
      decreased the discharge rate of wake-related neurons. Of 24 wake-related neurons
      studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge
      in the presence of IL-1 during waking. IL-1 suppressed the discharge activity of
      18 of 19 responsive neurons. Of 13 sleep-related neurons studied, IL-1 increased
      the discharge activity of five and suppressed the discharge activity of four
      neurons. IL-1ra increased the discharge activity of four of nine neurons and
      significantly attenuated IL-1-induced effects on neuronal activity of POA/BF
      neurons (n = 19). These results suggest that the sleep-promoting effects of IL-1
      may be mediated, in part, via the suppression of wake-related neurons and the
      activation of a subpopulation of sleep-related neurons in the POA/BF.

PMID- 15245494
TI  - Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like
      symptomatology.
AB  - We recently found that female aromatase knockout (ArKO) mice that are deficient
      in oestradiol due to a targeted mutation in the aromatase gene show deficits in
      sexual behaviour that cannot be corrected by adult treatment with oestrogens. We
      determined here whether these impairments are associated with changes in general
      levels of activity, anxiety or 'depressive-like' symptomatology due to chronic
      oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild
      type (WT) females, as oestrogens have been shown to modulate dopaminergic,
      serotonergic and noradrenergic brain activities. ArKO females did not differ from
      WT in spontaneous motor activity, exploration or anxiety. These findings are in
      line with the absence of major neurochemical alterations in hypothalamus,
      prefrontal cortex or striatum, which are involved in the expression of these
      behaviours. By contrast, ArKO females displayed decreased active behaviours, such
      as struggling and swimming, and increased passive behaviours, such as floating,
      in repeated sessions of the forced swim test, indicating that these females
      exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not
      reverse the behavioural deficits observed in the forced swim test, suggesting
      that they may be due to the absence of oestradiol during development.
      Accordingly, an increased serotonergic activity was observed in the hippocampus
      of ArKO females compared with WT, which was also not reversed by adult oestradiol
      treatment. The possible organizational role of oestradiol on the hippocampal
      serotonergic system and the 'depressive-like' profile of ArKO females provide new
      insights into the pathophysiology of depression and the increased vulnerability
      of women to depression.

PMID- 15245495
TI  - Does amygdaloid corticotropin-releasing hormone (CRH) mediate anxiety-like
      behaviors? Dissociation of anxiogenic effects and CRH release.
AB  - The brain corticotropin-releasing hormone (CRH) circuits are activated by
      stressful stimuli, contributing to behavioral and emotional responses. The
      present study assessed anxiety-like responses and in vivo neurochemical
      alterations at the central nucleus of the amygdala (CeA) evoked by exposure to an
      unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments
      and those that affect CRH were assessed in this paradigm. Novel environment (new
      cage) markedly suppressed ingestion of a palatable snack. This effect was dose
      dependently antagonized by diazepam and was utilized as an index of anxiety in
      the rodent. Although exposure to a novel environment also stimulated the in vivo
      release of CRH and glutamate at the CeA, various CRH antagonists (e.g. alphah
      CRH, Calpha-MeCRH, CP-154,526, antisauvagine-30, preproTRH178-199) did not
      attenuate the stressor-elicited behavioral suppression, although Calpha-MeCRH was
      found to attenuate the freezing response elicited by contextual stimuli that were
      associated with previously administered footshock. Moreover, central infusion of
      CRH failed to suppress snack consumption in the home cage. Although diazepam had
      potent anxiolytic effects in this paradigm, this treatment did not prevent the
      stressor-associated release of CRH and glutamate at the CeA. Thus, while neural
      circuits involving CRH and/or glutamatergic receptors at the CeA may be activated
      by an unfamiliar environment, the data challenge the view that activation of
      these receptors is necessary for the expression of anxiety-like behavioral
      responses. Rather than provoking anxiety, these systems might serve to draw
      attention to events or cues of biological significance, including those posing a
      threat to survival.

PMID- 15245496
TI  - Amygdala central nucleus function is necessary for learning but not expression of
      conditioned visual orienting.
AB  - When exposed to pairings of a visual stimulus with food delivery, rats normally
      acquire both conditioned orienting responses directed toward the visual stimulus
      and conditioned food-related responses. Consistent with the results of previous
      lesion studies, reversible inactivation of amygdala central nucleus function
      before each conditioning session prevented the acquisition of conditioned
      orienting responses, whereas food-related behaviors were acquired normally. By
      contrast, neither inactivation nor neurotoxic lesions of central nucleus affected
      the expression of previously acquired conditioned orienting responses. Thus, the
      central nucleus is apparently not critical to the maintenance of information
      required for conditioned orienting, but instead is necessary for memory storage
      elsewhere. Specialized roles for components of a circuit for conditioned
      orienting, which includes the central nucleus, the substantia nigra, and
      dorsolateral striatum, are discussed.

PMID- 15245497
TI  - Contrasting effects of dopamine and glutamate receptor antagonist injection in
      the nucleus accumbens suggest a neural mechanism underlying cue-evoked goal
      directed behavior.
AB  - Discriminative stimuli (DSs) inform animals that reward can be obtained
      contingent on the performance of a specific behavior. Such stimuli reinstate drug
      seeking behavior, evoke dopamine release in the nucleus accumbens (NAc) and
      excite and inhibit specific subpopulations of NAc neurons. Here we show in rats
      that DSs can reinstate food-seeking behavior. In addition, we compare the effects
      of injecting dopamine receptor antagonists into the NAc with those of general NAc
      inactivation on the performance of a DS task. Selective antagonism of D1
      receptors reduced responding to the DS and increased the latency to respond,
      whereas general inactivation of NAc neuronal activity increased the latency to
      respond to the DS and increased behaviors extraneous to the task, such as
      responding in the absence of cues and responding on the inactive lever. Based on
      these results and our previous findings that NAc neuronal responses to DSs are
      dependent on the ventral tegmental area, we propose a model for the functional
      role of NAc neurons in controlling behavioral responses to reward-predictive
      stimuli.

PMID- 15245498
TI  - Microstimulation of V1 delays the execution of visually guided saccades.
AB  - Electrical stimulation delivered to V1 concurrently with the presentation of a
      visual target interferes with both the selection and the detection of targets
      positioned in the receptive field of the stimulated neurons. In the present
      study, we examined the temporal course of this effect by delivering electrical
      stimulation to V1 of rhesus monkeys at various times before the appearance of a
      visual target. Each trial was initiated by the appearance of a fixation spot
      that, once acquired, was followed by the presentation of a visual target in the
      receptive field of the stimulated neurons. A monkey was reward after making a
      saccadic eye movement to the target. A delay in saccade generation was obtained
      when stimulation was delivered while an animal maintained fixation on the
      fixation spot. No delay occurred when the visual target was placed outside the
      receptive field of the stimulated neurons. The best parameters for inducing the
      saccadic delay were: (i). anode-first pulses (as opposed to cathode-first pulses)
      and (ii). train durations greater than 40 ms and frequencies greater than 100 Hz.
      The lowest current threshold for producing a saccadic delay occurred at 1.5 mm
      below the top of superficial V1. The chronaxies of the directly stimulated
      elements mediating the delay ranged from 0.13 to 0.24 ms. These values overlap
      with those that have been described for phosphene induction in human V1. We
      discuss how the elements mediating the saccadic delay might interrupt a visual
      signal as it passes along the geniculostriate pathway.

PMID- 15245499
TI  - The basolateral complex of the amygdala mediates the modulation of intracranial
      self-stimulation threshold by drug-associated cues.
AB  - Learning and memory appear to be critical aspects of drug abuse; presumably
      playing an especially important role in craving and relapse. Thus, understanding
      the interaction of learning- and memory-related brain areas with the classical
      reward circuitry is of importance. Toward this goal, the effect of drug
      associated contextual cues on intracranial self-stimulation (ICSS) behaviour was
      assessed in rats. We used a method that allows the establishment of baseline
      behaviour, the pairing of drug exposure with unique cues, and testing the effect
      of cue exposure within the same apparatus. ICSS thresholds were decreased by
      morphine (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired
      drug-cue training sessions. Subsequent presentation of the drug-associated cues
      decreased thresholds in the absence of drug. Cues associated with saline had no
      effect. These results suggest a Pavlovian conditioning phenomenon in which the
      functioning of brain reward circuitry is modulated by drug-associated cues. In a
      second experiment, we tested the hypothesis that the mechanism by which
      conditioning affects ICSS thresholds may include the basolateral complex of the
      amygdala (BLC) due to its known role in conditioning and anatomical linkage with
      classical reward circuitry. Lesions of the BLC abolished the ability of cocaine
      associated cues to lower ICSS threshold. Lesions did not alter response
      capability or the unconditioned effect of cocaine. We conclude that the BLC is
      necessary for cues associated with previous drug exposure to modulate activity
      within or downstream from the classical reward circuitry of the medial forebrain
      bundle.

PMID- 15245500
TI  - Context-independent directional cue learning by hippocampal place cells.
AB  - In a symmetrical environment possessing no other polarizing visual cues, the
      spatially localized firing of hippocampal place cells can be primarily orientated
      by a reliable distal visual stimulus, such as a white cue card. However, if such
      a directional cue is made unreliable by being frequently moved in full view of
      the rat, the rat's internal sense of direction comes, over the course of a few
      days, to control the orientation of place fields instead. We investigated whether
      this simple form of 'cue-instability' learning would transfer to a new context,
      in which the firing patterns of the place cells become reorganized and in which a
      new spatial representation is thus active. We found that after cue-instability
      learning, the 'remapped' place field representation in the new environment was
      also orientated by the internal sense of direction of the rat rather than by the
      cue card, showing that the cue learning generalized from one context (and hence
      spatial representation) to another. This contrasts with another kind of place
      cell learning, in which the cells can acquire the ability to discriminate two
      spatial locations in one context but do not transfer this discrimination to a new
      context. We discuss the different effects of context changes on learned place
      cell activity in terms of the possible architecture of the inputs to place cells.

PMID- 15245501
TI  - The distributed neuronal systems supporting choice-making in real-life
      situations: differences between men and women when choosing groceries detected
      using magnetoencephalography.
AB  - In this work, magnetoencephalography was used to study the temporal dynamics of
      neural responses in 16 subjects (eight women, eight men) choosing among different
      day-to-day consumer items. At short latencies (< 150 ms), the evoked responses
      showed striate and extrastriate cortical activation common to the processing of
      general objects. At about 300 ms, women activated preferentially left posterior
      cortices, whereas men activated preferentially right temporal cortices. This may
      reflect sex/gender differences in cognitive strategies, emphasizing category
      specific knowledge in women and spatial memories in men. At latencies greater
      than 500 ms, right parietal cortices were preferentially activated when
      previously bought or used items were chosen. In contrast, left inferior and right
      orbital cortices were preferentially activated when selecting less-known items.
      This may be interpreted as representing the neural correlates of decisions where
      the outcome is consistent with previous experience, and of choices which are
      'difficult' in some sense. Analysis of coherent gamma-oscillations (20-45 Hz)
      revealed neural activity over left anterior and right dorsolateral cortices at
      long latency (> 1500 ms) when brand knowledge is low. This is consistent with the
      late binding of (brand) memories and evaluation of multiple sources of
      information when a choice is not obvious. gamma-Activity showed that women may
      activate larger neural networks when preference is high, suggesting that men and
      women exhibit different patterns of neural activity even though their overt
      performances are similar.

PMID- 15245502
TI  - Abnormalities of presynaptic protein CDCrel-1 in striatum of rats reared in
      social isolation: relevance to neural connectivity in schizophrenia.
AB  - Post-weaning social isolation-rearing of rats leads to behavioural and
      neurochemical sequelae that model aspects of schizophrenia, and it may be useful
      to test hypotheses related to putative molecular mechanisms of the illness. In
      humans, the presynaptic protein CDCrel-1 represents an interesting candidate
      molecule for the mechanism and aetiology of schizophrenia. CDCrel-1 modulates
      dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a
      region of chromosome 22q11 deleted in velo-cardio-facial and DiGeorge syndromes,
      which are associated with increased prevalence of schizophrenia. Using the
      isolation-rearing model, we measured immunoreactivity of the synaptic proteins
      CDCrel-1, synaptophysin and syntaxin. Male, Sprague-Dawley rats were raised in
      groups or in isolation for 12 weeks from weaning. Synaptic protein
      immunoreactivities were measured in striatal and hippocampal homogenates, using a
      sensitive enzyme-linked immunoadsorbent assay with monoclonal antibodies.
      Isolation-rearing produced region- and protein-specific effects. CDCrel-1
      immunoreactivity was significantly lower in the striatum and marginally higher in
      the hippocampus of isolation-reared compared with socially reared animals. There
      were no statistically significant differences in synaptophysin immunoreactivity
      in either region. Confocal microscopy demonstrated a high degree of
      colocalization between the two presynaptic proteins. In striatum, a robust
      relationship between CDCrel-1 and syntaxin immunoreactivities was observed in
      socially reared rats, this was lost in the isolation-reared animals. Altered
      levels of the septin CDCrel-1 in isolation-reared rats may contribute to changes
      in neuronal connectivity and neurotransmission, and suggest a potential role for
      CDCrel-1 in schizophrenia related to chromosome 22q11 deletion syndrome.

PMID- 15245503
TI  - Impaired behavioural flexibility and memory in mice lacking GDNF family receptor
      alpha2.
AB  - The glial cell line-derived neurotrophic factor (GDNF) family receptor GFRalpha2
      is the binding receptor for neurturin (NRTN). The main biological responses of
      GFRalpha2 are mediated via the Ret receptor tyrosine kinase, although it may also
      signal independently of Ret via the neural cell adhesion molecule NCAM. GFRalpha2
      is expressed in many neurons of both the central and peripheral nervous system.
      Mice lacking GFRalpha2 receptors do not exhibit any gross defects in the central
      nervous system structure. However, they display profound deficits in the
      parasympathetic and enteric nervous system, accompanied by significant reduction
      in body weight after weaning. Here we present the results of behavioural analysis
      of the GFRalpha2-knockout mice. The knockout mice did not differ from wild-type
      mice in basic tests of motor and exploratory activity. However, differences were
      established in several memory tasks. The knockout mice were not impaired in the
      acquisition of spatial escape strategy. However, the deficit in flexibility in
      establishing a new strategy was revealed during reversal learning with the
      platform in the opposite quadrant of the pool. Furthermore, the knockout mice
      displayed significant impairment in contextual fear conditioning and conditioned
      taste aversion tests of memory. The results suggest that GFRalpha2 signalling
      plays a role in the development or maintenance of cognitive abilities that help
      in solving complex learning tasks.

PMID- 15245504
TI  - Transcranial direct current stimulation disrupts tactile perception.
AB  - The excitability of the cerebral cortex can be modulated by various transcranial
      stimulation techniques. Transcranial direct current stimulation (tDCS) offers the
      advantage of portable equipment and could, therefore, be used for ambulatory
      modulation of brain excitability. However, modulation of cortical excitability by
      tDCS has so far mostly been shown by indirect measures. Therefore, we examined
      whether tDCS has a direct behavioral/perceptional effect. We compared tactile
      discrimination of vibratory stimuli to the left ring finger prior to, during and
      after tDCS applied for 7 min at 1-mA current intensity in 13 subjects.
      Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a
      within-subject design. The active electrode was placed over the corresponding
      somatosensory cortex at C4 according to the 10-20 EEG system and the reference
      electrode at the forehead above the contralateral orbita. Cathodal stimulation
      compared with sham induced a prolonged decrease of tactile discrimination, while
      anodal and sham stimulation did not. Thus, cortical processing can be modulated
      in a behaviorally/perceptually meaningful way by weak transcranial current
      stimulation applied through portable technology. This finding offers a new
      perspective for the treatment of conditions characterized by alterations of
      cortical excitability.

PMID- 15245505
TI  - Defective long-term repopulating ability in hematopoietic stem cells lacking the
      Polycomb-group gene rae28.
AB  - The rae28 gene (rae28) is a member of a Polycomb-group (PcG) complex 1, which is
      known to help maintain transcription states once these have been initiated, by
      generating heritable higher-order chromatin structures. In this study, we
      examined the capacity of rae28-deficient (rae28-/-) hematopoietic stem cells
      (HSCs) to generate long-term marrow reconstitution. rae28-/- fetal liver cells
      containing 20 competitive repopulation units (CRUs) were able to support the
      survival of lethally irradiated congenic mice for as long as 6 months. The marrow
      reconstituted with the rae28-/- cells, however, could not increase HSCs
      efficiently. This was evidenced by its inability to reconstitute marrow in serial
      transplantation experiments, as well as by the reduction in HSC-enriched Lin- c
      kit+ Sca-1high+ subpopulation in the bone marrow cells. Moreover, the
      reconstituted marrow produced less than half of the peripheral blood cells in
      each of the lineages examined. We also monitored the mean stem cell activity
      (MAS). MAS of rae28-/- CRUs was progressively reduced after transplantation, and
      after 12 months it was reduced to one-tenth of that of the wild-type. These in
      vivo results clearly indicate that rae28 is indispensable for the long-term
      repopulating ability of HSCs. We further referred to the plausible mechanisms
      underlying defective long-term repopulating ability of rae28-deficient HSCs and
      argued for its involvement in maintenance of cell proliferation capability as
      well as that in self-renewal ability.

PMID- 15245506
TI  - Favourable outcome for patients with myeloid disorders treated with fludarabine
      melphalan reduced-intensity conditioning and allogeneic bone marrow stem cell
      transplantation without the use of T-lymphocyte-depleting antibodies.
AB  - We report the use of reduced-intensity conditioning (RIC)-matched sibling
      allogeneic bone marrow stem cell transplantation as a method of establishing a
      graft-vs.-leukaemia (GvL) effect against myeloid disorders using a fludarabine
      melphalan protocol without the use of T-lymphocyte-depleting antibodies. The 16
      patients in this group had predominantly poor-risk acute myeloid leukaemia (AML)
      (n=10), AML/myelodysplasia (MDS) (n=2) and MDS (n=4). All but one patient
      achieved full haematopoietic engraftment. Thirteen of 16 patients are alive and
      in continued complete remission on completion of this study with a median follow
      up of 426 d (range 83-1524). The actuarial 4 yr disease-free and overall survival
      is 79% for both. Only one patient relapsed following transplant, giving a relapse
      rate of 6% during the study period. The treatment-related mortality was 13% (n=
      2). Overall, acute graft-vs.-host disease (GvHD) occurred in 53% (8/15), with
      acute GvHD grade II or above occurring in 47% (7/15). In the 13 evaluable
      patients, chronic GvHD occurred in 46% (6/13), with this being extensive in three
      patients. These results suggest that a GvL effect can be delivered against poor
      risk myeloid disorders with a low non-relapse mortality using this fludarabine
      melphalan RIC protocol.

PMID- 15245507
TI  - Clinical, haematological and histomorphological profile of adult myelodysplastic
      syndrome. Study of 96 cases in a single institute.
AB  - Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders
      characterised by ineffective and dyspoietic haematopoiesis. The natural history
      of these disorders is variable and ranges from a chronic to a rapid course
      towards leukaemic progression. Certain shortcomings have been encountered in the
      French-American-British (FAB) classification over the years, and therefore there
      is a need for an alternative method of classification. In 1999, the WHO published
      a revised classification of MDS. In the present study, we have analysed the
      clinical, haematological and histomorphological features in 96 cases of primary
      MDS seen in the department of haematology at the All India Institute of Medical
      Sciences (AIIMS) over a 6-yr period (1996-2001). Both FAB and WHO classifications
      have been incorporated and the Bournemouth scoring system applied in each case at
      presentation. The Bournemouth scoring system, in the absence of a cytogenetic
      study, offers a good prognostication and long-term survival estimate.

PMID- 15245508
TI  - Thalidomide alone or in combination with dexamethasone in patients with advanced,
      relapsed or refractory multiple myeloma and renal failure.
AB  - Salvage therapy of patients with advanced, relapsed and refractory multiple
      myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment.
      In particular, renal failure occurs in up to 50% of such patients, and this
      further limits the use of conventional chemotherapy. Thalidomide, both alone and
      in combination with dexamethasone, has been demonstrated to be useful in patients
      with advanced MM, as responses could be achieved in 30-60% of the cases. From May
      2000 to November 2003, 20 consecutive MM patients (15 males, five females, median
      age 66.5 yr) with stage III relapsed/refractory MM and renal failure, defined as
      serum creatinine >130 mmol/L, gave their informed consent to be enrolled in a
      clinical trial aimed at evaluating the efficacy and the toxic effects of
      thalidomide. Three patients were undergoing chronic haemodialysis during the time
      of entry in the study. Eight patients have been treated with thalidomide as a
      single agent, at a starting dose of 100 mg/d, that was to be increased to 400
      mg/d in case of good tolerance. Twelve patients have been treated with
      thalidomide at the maximum dose of 200 mg/d plus dexamethasone 40 mg/d for four
      consecutive days every 4 wk. A >50% decrease in serum or urine M component was
      observed in nine patients (45%), seven of whom have been treated with thalidomide
      + dexamethasone and three with thalidomide alone. Six additional patients
      achieved a minor response (>25% paraprotein decrease); the total response rate
      was thus 75%. Median response duration was 7 months (range 2-24 months). Four
      patients were refractory to treatment. Recovery of a normal renal function was
      observed in 12 of 15 responsive patients, two additional patients, in chronic
      haemodialysis, showed a reduction of serum creatinine. Toxicity profile of
      thalidomide with or without dexamethasone was comparable with that observed in
      patients with a normal renal function. In conclusion, our data show that
      thalidomide can be safely administered in patients with advanced MM and renal
      failure.

PMID- 15245509
TI  - Perioperative venous thromboembolism prophylaxis in Israel: a survey of academic
      surgical departments.
AB  - OBJECTIVE: Postoperative venous thromboembolism (VTE) represents a serious threat
      to patients undergoing surgical procedures. Without thromboprophylaxis, deep vein
      thrombosis occurs in up to 60% of patients undergoing major orthopedic surgery
      and 15% of patients undergoing major abdominal surgery. Although, many studies
      have shown the efficacy of pharmacologic and mechanical means of VTE prophylaxis,
      practice variations in this area abound worldwide. The purpose of this study was
      to determine the attitudes and practice of VTE prophylaxis of academic surgical
      department heads in Israel. METHODS: A questionnaire covering various aspects of
      VTE prophylaxis was mailed to all surgical department heads of university
      teaching hospitals in Israel. Three months later, the same questionnaire was sent
      to department heads who had not yet replied. Data retrieved from the returned
      questionnaires were analyzed. RESULTS: A total of 250 departments in 23 hospitals
      affiliated to the four medical schools in Israel were identified; 130 department
      heads (52%) returned the questionnaires. The current study analyzes results
      obtained from the general surgical, orthopedic, urological, vascular and
      gynecological departments only. The total number of responses from these
      departments was 90 (69% response rate). Sixty-seven percent of the departments
      considered VTE to be a clinical problem. Ninety-four percent of departments have
      a policy for VTE prophylaxis. The most frequently used modalities for VTE
      prophylaxis (more than one option possible) were low-molecular-weight heparin
      (LMWH) (59%), unfractionated heparin (43%) and an intermittent pneumatic
      compression device (20%). VTE prophylaxis is begun 12 h preoperatively by 33% of
      departments, 2-4 h preoperatively by 20% of departments and with premedication by
      8% of departments. VTE prophylaxis was continued during the postoperative period
      by all departments, with 52% stopping prophylaxis upon patient mobilization.
      Bleeding complications have been noted by 55% of departments, of these 9% were
      considered major. In general surgical, orthopedic and gynecologic departments,
      VTE prophylaxis was widely used for those procedures for which published
      guidelines exist, while considerable variation in VTE prophylaxis administration
      was demonstrated in a number of commonly encountered clinical situations for
      which there are no published recommendations. CONCLUSIONS: This study confirms
      that academic surgical departments in Israel conform to standard VTE prophylaxis
      guidelines. However, considerable variations in practice exist regarding the
      means of prophylaxis, onset of prophylaxis and its duration. These areas should
      be the focus of ongoing educational efforts including the development of uniform
      practice guidelines to improve the quality of care regarding VTE prophylaxis.
      Furthermore, attention should be given to methods for decreasing hemorrhage
      caused by LMWH and unfractionated heparin usage.

PMID- 15245510
TI  - Macrophages in spleen and liver direct the migration pattern of rat neutrophils
      during inflammation.
AB  - OBJECTIVE: The exact fate of polymorphonuclear neutrophilic granulocytes (PMN;
      neutrophils) after their mobilization from the bone marrow is not known. It is
      believed that they, after a relatively short lifespan (1-3 d), become apoptotic
      and phagocytosed by macrophages. We have recently shown that transfused
      neutrophils sequestrate not only in lungs, liver and spleen, but also to a large
      extent in the bone marrow, possibly because of uptake by macrophages. Hence, we
      studied if inactivation of macrophages would alter the pattern of neutrophil
      migration. METHODS: We used transfused congenic or syngeneic neutrophils in rats
      with or without sterile peritonitis, induced by a casein preparation (Bacto
      Tryptone). To perturb macrophage function, we either killed them with liposome
      encapsulated clodronate or overloaded them with inert phagocytosable particles.
      Transfused neutrophils were tracked with flow cytometric or radiometric methods.
      RESULTS: Not more than a small portion of the neutrophils migrated to the
      inflamed peritoneal cavity under any circumstance. Their ecotaxis to liver and
      spleen was reduced in rats with liver and spleen macrophages either congested
      with polystyrene particles or depleted by clodronate. The bone marrow uptake and
      blood retention of transfused neutrophils were increased in macrophage-depleted
      rats 18 h after transfusion. In rats depleted of liver macrophages only, the
      sequestration in the liver was reduced, without detectably changed uptake in bone
      marrow and spleen. CONCLUSION: Macrophages are instrumental to the neutrophil
      migration stream in the organism, and their function in this regard is robust and
      not easily decreased by inert phagocytosable particles or a killing agent.

PMID- 15245511
TI  - Periodic fever, mild arthralgias, and reversible moderate and severe organ
      inflammation associated with the V198M mutation in the CIAS1 gene in three German
      patients--expanding phenotype of CIAS1 related autoinflammatory syndrome.
AB  - Dominant mutations in the CIAS1 gene cause a spectrum of autoinflammatory
      diseases such as familial cold autoinflammatory syndrome, FCAS, which is
      characterized by episodes of urticaria, arthralgia, fever and conjunctivitis
      after generalized exposure to cold. We here describe patients of two German
      families with the 592G-->A, V198M mutation, which has been described to induce
      FCAS before. However, in our patients the clinical phenotype was very different
      from this disease. They never had urticaria, cold induced fever or
      conjunctivitis; instead the following symptoms occurred: Very regular periodic
      fever, irregular severe febrile episodes, relatively mild arthralgia, dry cough,
      cardiomyopathy, nephropathy and euthyroid thyroiditis all being reversible. We
      conclude that the clinical phenotype associated with mutations in the CIAS1 gene
      is much broader than assumed before.

PMID- 15245512
TI  - Large-vessel arteritis and myelodysplastic syndrome: report of two cases.
AB  - Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases
      such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The
      pathogenesis of these autoimmune complications remains unknown, but there is
      increasing evidence of profound immune dysregulation in MDS. In the few cases
      reported so far, vasculitides associated with MDS affected mainly cutaneous
      vessels. Here we describe two cases of acute large-vessel vasculitis in
      association with MDS. The first patient is a 67-yr-old male presenting with a
      massive large-vessel arteritis as primary manifestation of refractory anemia with
      excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who
      presented with acute thoracic aortitis after a 2-yr history of refractory anemia
      with ringed sideroblasts (RARS). Both patients received immunosuppressive
      treatment with steroids, leading to rapid improvement of systemic inflammatory
      symptoms, vessel wall injury and peripheral blood counts. Whereas the first
      patient displayed sustained favorable hematologic responses under long-term
      steroid therapy, there was a rapid transformation into secondary acute myeloid
      leukemia in the second patient. We conclude that large-vessel vasculitis should
      be added to the list of potential autoimmune complications in MDS. In this
      clinical setting, steroid therapy may alleviate inflammatory symptoms and result
      in beneficial hematologic responses.

PMID- 15245513
TI  - Rapidly progressive diffuse large B-cell lymphoma with initial clinical
      presentation mimicking seronegative Wegener's granulomatosis.
AB  - Here we present a 40-yr-old male patient with an aggressive B-cell lymphoma, who
      presented 2 yr earlier with polyarthritis, and was responsive to steroids and
      oral methotrexate. Thereafter he developed skin and lung lesions which on biopsy
      consisted of mixed 'inflammatory' infiltrates with granulomatous vasculitis. A
      diagnosis of seronegative Wegener's granulomatosis was made and the patient
      received a combination of prednisone and cyclophosphamide with clinical
      improvement and clearance of the radiological lesions in the lungs. The patient
      was now completely asymptomatic for 1 yr, but then generalized lymphadenopathy
      appeared, which was shown by histopathology to be large B-cell lymphoma, also
      involving the bone marrow. Despite intensive chemotherapy, his disease could not
      be controlled because of primary chemoresistance, which was perhaps in some way
      related to exposure to the suboptimal doses of chemotherapy given during the
      'inflammatory' period before the diagnosis of lymphoma was established. This case
      illustrates the occasional difficulty in distinguishing between extranodal
      lymphoproliferative diseases and autoimmune disorders especially when clonality
      cannot be proved. It also shows the possible risk of 'masking' a true lymphoma by
      treating non-malignant diseases with immunosuppressive agents, which may
      eventually contribute to the development of chemoresistant lymphoma.

PMID- 15245514
TI  - Bronchiolitis obliterans organizing pneumonia following chlorambucil treatment
      for chronic lymphocytic leukemia.
AB  - A 70-yr-old man developed cough, chest pain, hemoptysis and a pulmonary
      infiltrate shortly after initiation of treatment with chlorambucil for chronic
      lymphocytic leukemia. Chlorambucil was discontinued and an open lung procedure
      was performed with complete excision of the pulmonary lesion. The biopsy
      specimens showed histological alteration consistent with the diagnosis of
      bronchiolitis obliterans organizing pneumonia (BOOP). There was no evidence of
      other known causes usually associated with BOOP. The patient recovered completely
      after surgery. This report suggests that BOOP must be considered in the
      differential diagnosis of respiratory symptoms and pulmonary infiltrates in
      patients treated with chlorambucil.

PMID- 15245516
TI  - Successful treatment of advanced idiopathic myelofibrosis with imatinib mesylate.

PMID- 15245515
TI  - A rare case of interstitial pneumonitis after tandem high-dose melphalan
      conditioning and autologous stem cell transplantation in multiple myeloma.
AB  - A 57-yr-old woman with multiple myeloma received an autologous tandem transplant
      at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After
      the second transplant, interstitial pneumonitis (IP) ensued. The clinical course
      was life threatening and mechanical ventilation was required for 32 d. All
      attempts to identify an infectious agent failed. A presumptive diagnosis of
      idiopathic IP, possibly related to melphalan toxicity, was made. High-dose
      methylprednisolone administration led to rapid and durable improvement. Melphalan
      was employed for conditioning in the tandem setting with an interval of only 3-4
      months between two courses or a dose elevation to 225 instead of 200 mg/m2, may
      have induced IP which responded favorably to methylprednisolone.

PMID- 15245517
TI  - Nigerian dentists' knowledge and attitudes towards mouthguard protection.
AB  - The objective of this study was to assess the knowledge and attitudes of Nigerian
      dentists towards mouthguard protection. A pre-tested 15-item, one-page
      questionnaire was distributed to 185 dentists practising in different parts of
      the country with government hospitals or private establishments, by 'hand
      delivery' system. Filled and returned forms were 170 (response rate of 92%). The
      period of the survey was between April and August 2003. Dental graduates from the
      different dental schools in the country responded to this survey. About 49% of
      the respondents indicated having only classroom lectures on mouthguards during
      their undergraduate trainings, 11% said they had some laboratory sessions in
      addition while no form of education on mouthguards was received by 40%. About 82%
      had never recommended mouthguard protection for athletic patients, and the major
      reason was no formal training in the subject. Only 58.5% were familiar with the
      different types of mouthguards, 75.9% would not be able to supervise or fabricate
      mouthguards and 50.6% would prefer custom-made mouthguard for their athletic
      patients. About 84% felt the current training on mouthguards in Nigerian dental
      schools is inadequate. Over 98% agreed that mouthguard usage in contact sports
      should be encouraged with the involvement of the dentists. The knowledge and
      attitudes of the respondents towards mouthguard protection did not vary
      significantly across years of postqualification from dental schools as well as
      the professional status of the dentists (P > 0.05). Although Nigerian dentists
      support mouthguard protection in contact sports and want to be involved in the
      provision of mouthguards for athletes, their knowledge of the protective device
      is inadequate. There is need for attention to be given to this subject in the
      undergraduate curricula of our dental schools.

PMID- 15245518
TI  - Healing of 400 intra-alveolar root fractures. 1. Effect of pre-injury and injury
      factors such as sex, age, stage of root development, fracture type, location of
      fracture and severity of dislocation.
AB  - This retrospective study consisted of 400 root-fractured, splinted or non
      splinted incisors in young individuals aged 7-17 years (mean = 11.5 +/- 2.7 SD)
      who were treated in the period 1959-1995 at the Department of Pediatric
      Dentistry, Eastman Dental Institute, Stockholm. Four hundred of these root
      fractures were diagnosed at the time of injury; and 344 teeth were splinted with
      either cap-splints, orthodontic appliances, bonded metal wires, proximal bonding
      with composite resin or bonding with a Kevlar or glass fiber splint. In 56 teeth,
      no splinting was carried out for various reasons. In the present study, only pre
      injury and injury factors were analyzed. In a second study, treatment variables
      will be analyzed. The average observation period was 3.1 years +/- 2.6 SD. The
      clinical and radiographic findings showed that 120 teeth out of 400 teeth (30%)
      had healed by hard tissue fusion of the fragments. Interposition of periodontal
      ligament (PDL) and bone between fragments was found in 22 teeth (5%), whereas
      interposition of PDL alone was found in 170 teeth (43%). Finally, non-healing,
      with pulp necrosis and inflammatory changes between fragments, was seen in 88
      teeth (22%). In a univariate and multivariate stratified analysis, a series of
      clinical factors were analyzed for their relation to the healing outcome with
      respect to pulp healing vs. pulp necrosis and type of healing (hard tissue vs.
      interposition of bone and/or PDL or pulp necrosis). Young age, immature root
      formation and positive pulp sensibility at the time of injury were found to be
      significantly and positively related to both pulpal healing and hard tissue
      repair of the fracture. The same applied to concussion or subluxation (i.e. no
      displacement) of the coronal fragment compared to extrusion or lateral luxation
      (i.e. displacement). Furthermore, no mobility vs. mobility of the coronal
      fragment. Healing was progressively worsened with increased millimeter diastasis
      between fragments. Sex was a significant factor, as girls showed more frequent
      hard tissue healing than boys. This relationship could possibly be explained by
      the fact that girls experienced trauma at an earlier age (i.e. with more immature
      root formation) and their traumas were of a less severe nature. Thus, the pre
      injury or injury factors which had the greatest influence upon healing (i.e.
      whether hard tissue fusion or pulp necrosis) were: age, stage of root development
      (i.e. the size of the pulpal lumen at the fracture site) and mobility of the
      coronal fragment, dislocation of the coronal fragment and diastasis between
      fragments (i.e. rupture or stretching of the pulp at the fracture site).

PMID- 15245519
TI  - Healing of 400 intra-alveolar root fractures. 2. Effect of treatment factors such
      as treatment delay, repositioning, splinting type and period and antibiotics.
AB  - This is the second part of a retrospective study of 400 root-fractured permanent
      incisors. In this article, the effect of various treatment procedures is
      analyzed. Treatment delay, i.e. treatment later than 24 h after injury, did not
      change the root fracture healing pattern, healing with hard tissue between
      fragments (HH1), interposition of bone and/or periodontal ligament (PDL) or pulp
      necrosis (NEC). When initial displacement did not exceed 1 mm, optimal
      repositioning appeared to significantly enhance both the likelihood of pulpal
      healing and hard tissue repair (HH1). Significant differences in healing were
      found among the different splinting techniques. The lowest frequency of healing
      was found with cap splints and the highest with fiberglass or Kevlar splints. The
      latter splinting procedure showed almost the same healing result as non
      splinting. Comparison between non-splinting and splinting for non-displaced teeth
      was found to reveal no benefit from splinting. With respect to root fractures
      with displacement, too few cases were available for analysis. No beneficial
      effect of splinting periods greater than 4 weeks could be demonstrated. The
      administration of antibiotics had the paradoxical effect of promoting both HH1
      and NEC. No explanation could be found. It was concluded that, optimal
      repositioning seems to favor healing. Furthermore, the chosen splinting method
      appears to be related to healing of root fractures, with a preference to pulp
      healing and healing fusion of fragments to a certain flexibility of the splint
      and possibly also non-traumatogenic splint application. Splinting for more than 4
      weeks was not found to influence the healing pattern. A certain treatment delay
      (a few days) appears not to result in inferior healing. The role of antibiotics
      upon fracture healing is questionable.

PMID- 15245520
TI  - The biomechanical properties of the healing periodontium of replanted rat
      mandibular incisors.
AB  - One of the most important aspects in tooth replantation seems to be restoration
      of the tooth support function of the healing periodontal ligament (PDL). We
      examined the support function, as measured by the mechanical properties, of the
      healing PDL at 7, 14, and 21 days after replantation of the left mandibular
      incisor in rats. From each dissected left mandible, a transverse section(650
      microm in thickness) of the incisor was cut through an axis near the labial
      alveolar crest. Each section was intrusively loaded at a rate of 5 mm min(-1),
      and the shear stress-strain curve for the PDL was analyzed. Mechanical measures
      of the healing PDL showed gradual improvement after replantation. By 21 days, the
      mechanical strength returned to 53% of the control value; the extensibility, to
      85%; the stiffness, to 61%; and the toughness, to 52%. The healing PDL exhibited
      reattachment of fibers in the middle region of the PDL, and the birefringent
      collagen fibers appeared to have regained the functional orientation by 14 days.
      The ratios occupied by the birefringent collagen fibers in the tooth-related,
      middle, and bone-related areas of the healing PDL gradually improved and returned
      to 78, 51, and 48% of the respective control values by 21 days. These results
      suggest that the support function of the healing PDL is gradually restored and
      that the biomechanical restoration is closely related to the reorganization and
      reorientation of collagen fiber bundles in replanted rat incisors.

PMID- 15245521
TI  - Management of a complex dentoalveolar trauma with multiple avulsions: a case
      report.
AB  - Treatment of permanent tooth avulsions in an adolescent poses significant
      difficulties for the dental clinician. This case report gives details about the
      treatment of a complex dentoalveolar trauma involving multiple avulsions of
      primary molars, permanent incisors, permanent molars, and premolar toothbuds.
      Immediate treatment of the injury and short-term esthetic replacement of the
      dentition is described. A brief review of current research relative to the
      treatment of permanent tooth avulsions is provided.

PMID- 15245523
TI  - Re-eruption of traumatically intruded mature permanent incisor: case report.
AB  - This case report describes a case of intrusion of the right mature permanent
      central incisor. After gingivectomy and endodontic treatment with changes of the
      intracanal dressing (calcium hydroxide paste) every 30 days, spontaneous re
      eruption was observed. We conclude that waiting for spontaneous re-eruption
      associated with gingivectomy and endodontic treatment is an alternative treatment
      for severe intrusive luxations in mature permanent teeth.

PMID- 15245522
TI  - Successful treatment of a radicular groove by intentional replantation and
      Emdogain therapy.
AB  - Radicular groove is an anatomical malformation often predisposing to a severe
      periodontal defect. Treatment of such an anomaly presents a clinical challenge to
      the operator. Presented is a case of successful treatment of a radicular groove
      associated with a maxillary lateral incisor in a 15-year-old girl. A combination
      of endodontic, intentional replantation and Emdogain therapy was used. At 1-year
      follow-up, the patient was comfortable and active healing was evident.

PMID- 15245524
TI  - Infected immature teeth treated with surgical endodontic treatment and root
      reinforcing technique with glass ionomer cement.
AB  - The authors propose surgical endodontic treatment of immature teeth characterized
      by necrosis and infection, especially after failure of apexification or in the
      presence of older, fibrous, and extensive lesion. A glass ionomer cement,
      autopolymerizable and condensable, is used as retro-filling material and as a
      reinforcement material for the canal walls. The variety of different cases
      presented here show that this rapid technique is reliable and reproducible.

PMID- 15245526
TI  - A pilot study on the use of wet wraps in infants with moderate atopic eczema.
AB  - Wet wrap therapy (WWT) is a well-established treatment for severe atopic
      dermatitis (AD). However little evidence exists to justify widespread use in the
      community for less severe eczema. We compared the efficacy of WWT with a standard
      regime of hydrocortisone, to control moderate AD in children. We carried out a
      single-observer, randomized, controlled pilot study in 19 children under 5 years
      of age, with AD of 30% or more body surface area, using only 1% hydrocortisone
      (HC) prior to the study. Group one applied HC once in the morning for 2 weeks,
      with wet wraps twice daily for week 1, but only at night for week 2. Group two
      applied HC twice daily without wet wraps. Both applied emollient twice daily and
      as necessary. The primary outcome measure was the Six Area, Six Sign Atopic
      Dermatitis (SASSAD) severity score, and the secondary outcome measures were the
      Infants Dermatology Quality of Life Index (IDQOL), the Dermatitis Family Impact
      (DFI) score and the weight of topical steroids and emollients used. Over the 2
      week active therapy period the mean fall in SASSAD was 8 [95% confidence interval
      (CI), -18 to +2; P = 0.11] more in the non-WWT group, the median change in the
      IDQOL was 2 for Group one and 7 for Group two (95% CI for difference, -10 to +3;
      P = 0.24) and the median change in DFI score was 2 for Group one and 5 for Group
      two (95% CI for difference, -14 to +2; P = 0.42). This small study has shown that
      conventional therapy with HC and emollients alone is as effective as WWT for
      infants with moderately severe, widespread AD, and provides weak evidence to
      suggest that it may be more effective. We would not advocate routine use of WWT
      for moderate eczema without further evaluation.

PMID- 15245527
TI  - Psoriasis associated with vulval scarring.
AB  - Psoriasis is a chronic inflammatory skin disorder which is generally not
      associated with scarring. We report two patients with long-standing severe
      anogenital psoriasis, that was associated with loss of the labia minora, thus
      clinically mimicking the scarring associated with lichen sclerosus.
      Histopathological finding were however, consistent with psoriasis with no
      evidence of lichen sclerosus. Elastic fibres were present and there was no
      evidence of abnormal collagen or fibrous tissue. The association of vulval
      psoriasis with scarring has not been reported previously.

PMID- 15245528
TI  - Pyoderma gangrenosum associated with Takayasu's arteritis.
AB  - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by
      destructive, necrotizing and noninfective ulceration of the skin mostly on lower
      extremities. PG is well known as a complication of Takayasu's arteritis in Japan.
      However, this association is not commonly observed in North American and European
      patients. We describe a case of PG that was associated with Takayasu's arteritis
      who was successfully treated with systemic cyclosporin. We have reviewed 35 well
      documented PG cases with Takayasu's arteritis in comparison to 106 PG cases
      without Takayasu's arteritis. The results demonstrate that this association
      occurs predominantly in young females and that these cases exhibit more
      widespread PG lesions.

PMID- 15245529
TI  - Scleroderma and the taxanes. Is there really a link?
AB  - Scleroderma has been associated with exposure to many substances in the past
      ranging from vinyl chloride to silicon dioxide. In recent years there have been a
      number of case reports linking modern chemotherapy agents, such as the taxanes to
      the development of scleroderma like changes. We present a further case of
      scleroderma in association with chemotherapy but question the role of some of the
      agents previously implicated. A brief review of the current literature is
      included.

PMID- 15245530
TI  - Co-existence of lichen amyloidosus and angiolymphoid hyperplasia with
      eosinophilia.
AB  - Summary Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign
      vascular tumour. It presents with small, dull red papules or nodules usually on
      the ears and preauricular areas and only 20% of lesions are multiple. We report a
      case of multiple scattered lesions of ALHE in a patient who subsequently
      developed lichen amyloidosus. Cases of lichen amyloidosus in association with
      Kimura's disease have been reported previously, but there are no reports of
      lichen amyloidosus with ALHE. The coexistence of these two conditions implies
      that ALHE is an inflammatory disorder, as an inflammatory process resulting in
      basal layer damage is necessary for the occurrence of lichen amyloidosus.

PMID- 15245531
TI  - A granulomatous response to tribal medicine as a feature of the immune
      reconstitution syndrome.
AB  - Summary Immune reconstitution is a well recognized phenomenon associated with the
      use of highly active antiretroviral therapy (HAART) for HIV infection. After the
      administration of HAART there is a rise in CD4 T-cell count in the circulation
      brought about by cessation of HIV replication. This allows the body to respond to
      antigens that it previously ignored. This manifests itself most commonly as an
      overt illness to previously ignored pre-existing infections such as Mycobacterium
      tuberculosis, herpes simplex virus, varicella zoster virus, hepatitis B and C
      viruses, cytomegalovirus, cryptococcal infection, human papilloma virus and
      molluscum contagiosum. There are further reports of reactions to sarcoid and
      tattoo pigment and one previous case reported of a granulomatous reaction to a
      foreign body. We report another case of a foreign body granuloma reaction, to
      tribal medicine implanted in tribal marks made in childhood in a Zimbabwean
      woman. This reaction is part of the immune reconstitution syndrome.

PMID- 15245532
TI  - Concurrent subcutaneous and visceral basidiobolomycosis in a renal transplant
      patient.
AB  - Basidiobolomycosis is a chronic inflammatory disease that occurs exclusively in
      healthy individuals. Clinically, the infection is generally restricted to
      subcutaneous tissue; however, the disease has been documented to emerge in
      visceral organs but seldom spreads to cause disseminated infection. We describe
      the first culture-confirmed case of systemic Basidiobolus ranarum infection in an
      immunosuppressed patient. A 55-year-old female renal transplant recipient
      developed chronic hard nonpitting oedema of the right lower extremity and
      abdominal wall concurrent with the infection from the same organism involving the
      uterus, urinary bladder and intra-abdominal lymph nodes. The patient responded
      successfully, both clinically and radiographically, to medical therapy without
      surgical resection. The treatment regimen consisted of potassium iodide and
      trimethoprim/sulfamethoxazole for 3 months, and the patient remains clear of
      symptoms after 10 months' follow-up.

PMID- 15245533
TI  - Multicentric reticulohistiocytosis with generalized systemic involvement.
AB  - We describe a 33-year-old woman with a 2-year history of rheumatoid arthritis
      like joint changes and a 1-year history of papulonodules on the fingers, ears,
      oral mucosa, forearm, elbows and thighs, and erythematous plaques on the
      buttocks. Six months after the onset of the cutaneous lesions she had dyspnoea, 3
      months later she developed a husky sound. Biopsies from the nodules on the ear
      and left forearm revealed multinucleated giant cells with eosinophilic 'ground
      glass' cytoplasm. Bronchoscopy revealed that there were nodules in the bronchus.
      A biopsy taken from a nodule from the bronchus was consistent with multicentric
      reticulohistiocytosis. Fibrostic laryngoscopy showed a mass 1.5 x 2.0 cm(2) in
      size on the left aryepiglottic fold and posterior commissure. Magnetic resonance
      imaging revealed a large pleural effusion and pericardiac effusion. Ultrasound
      revealed splenomegaly and peritoneal fluid. Combination therapy with prednisone,
      cyclophosphamide and methotrexate significantly improved cutaneous and joint
      symptoms. The huge cutaneous erythematous plaques and the generalized systemic
      involvement make this case interesting.

PMID- 15245534
TI  - Severe sporotrichoid infection with Mycobacterium szulgai.
AB  - Mycobacterium szulgai is a nontuberculous, acid-fast bacillus or atypical
      mycobacteria, which prior to 1972 was not thought of as a pathogen. Since then
      most cases reported in the literature have been of pulmonary disease with only a
      few case reports of cutaneous disease. Our patient, who had an underlying,
      uncategorized, immunosuppressive condition, presented with multiple severe ulcers
      spreading proximally up the arms in a sporotrichoid pattern with more scatttered
      lesions on his legs. He made a full recovery with appropriate antimicrobial
      treatment.

PMID- 15245535
TI  - Psoralen plus ultraviolet A irradiation-induced lentigines arising in vitiligo:
      involvement of vitiliginous and normal appearing skin.
AB  - Psoralen plus ultraviolet A irradiation (PUVA therapy) is commonly used for the
      management of vitiligo in which perifollicular repigmentation is the usual
      response pattern. However, excessive PUVA therapy may be associated with adverse
      effects. We report a case of generalized vitiligo that has been extensively
      treated with topical and systemic PUVA therapy for several years with the
      development of extensive and widespread stellate and irregularly shaped black and
      brown macules (lentigines). Interestingly, the lentigines were observed not only
      in the normally pigmented skin but also within the depigmented lesions that were
      lacking the perifollicular response pattern. The lesions developed in the exposed
      and unexposed skin areas. No evidence of skin malignancy was observed clinically
      and no melanocyte atypia was detected histopathologically. Cryotherapy may be
      used in the management of the lentigines; however, because of the extent of
      lesions this was impractical in our case.

PMID- 15245536
TI  - Evidence for polyclonal infection of Epstein-Barr virus in a patient with primary
      cutaneous anaplastic large cell lymphoma.
AB  - We report a case of CD30 + primary cutaneous anaplastic large cell lymphoma. The
      lymphoma cells were shown to express the Epstein-Barr virus (EBV)-encoded small
      RNAs by in situ hybridization and to have EBV genomes by PCR, whereas no
      monoclonal band was detected by Southern blot analysis using the EBV terminal
      repeat probe. These data suggested polyclonal infection by EBV, which provides
      evidence that EBV plays little part in the pathogenesis of this tumour even in
      the infected cases.

PMID- 15245537
TI  - Rheumatoid papules treated with dapsone.
AB  - A patient with a long history of seropositive rheumatoid arthritis presented with
      a progressive papular eruption on the trunk. A skin biopsy showed a neutrophilic
      and palisaded granulomatous dermatitis compatible with rheumatoid papules. The
      eruption failed to respond to topical and systemic corticosteroids and the
      patient was treated with dapsone with complete resolution of the rash. Rheumatoid
      papules are a rare disorder seen in a variety of collagen vascular diseases. The
      literature concerning the treatment of rheumatoid papules is scanty. In this
      patient, dapsone was an effective treatment.

PMID- 15245538
TI  - Purpura fulminans -- a novel presentation of Churg Strauss syndrome.
AB  - Purpura fulminans is a rare syndrome of haemorrhagic necrosis of the skin and
      intravascular thrombosis associated with disseminated intravascular coagulopathy.
      It has not previously been reported as a presenting feature of Churg Strauss
      syndrome.

PMID- 15245539
TI  - Systemic lupus erythematosus or infection with HIV, or both?
AB  - The features of both HIV infection and connective tissue disease are often
      nonspecific and may mimic other disorders as well as each other. We treated a
      patient with presumed systemic lupus erythematosus (SLE) for 4 years, who finally
      admitted to longstanding infection with HIV. The coexistence of SLE and HIV is
      unusual and has, although reported in the rheumatological journals, not often
      been discussed in the dermatological literature.

PMID- 15245540
TI  - Acneiform follicular mucinosis.
AB  - Follicular mucinosis is a rare chronic inflammatory disease of unknown aetiology,
      presenting as mucin deposits around the follicles and sebaceous glands. It can
      progress to alopecia of the scalp and other hairy areas. Follicular mucinosis may
      be a benign primary idiopathic disorder or secondary to malignant
      lymphoproliferative disorders. It can present with shiny papules or sharply
      marginated infiltrated erythematous scaling plaques, with follicular accentuation
      on the scalp, neck, trunk and limbs. There are many local and systemic
      treatments. This paper discusses the case of an adult with an uncommon acneiform
      follicular mucinosis controlled with systemic corticosteroids.

PMID- 15245541
TI  - Haplotype associations of the MHC with psoriasis vulgaris in Chinese Hans.
AB  - Summary Haplotype associations of the major histocompatibility complex (MHC) with
      psoriasis vulgaris (PV) have been demonstrated in different racial or ethnic
      populations. The objective of this study was to demonstrate the different
      haplotype associations of the MHC in Chinese patients with psoriasis according to
      the type of onset and their sex. One hundred and thirty-eight patients with PV
      and 149 normal control subjects without psoriasis were typed for HLA-A, -B, -C, 
      DQA1, -DQB1 and -DRB1 by using the PCR with sequence-specific primers. The
      results showed: (i) HLA-A*26 (26.1% vs. 12.1%, Pc < 1 x 10(-5)), -B*27 (17.03%
      vs. 1.01%, Pc < 1 x 10(-7)), -Cw*0602 (15.58% vs. 5.03%, Pc < 1 x 10(-2)), 
      DQA1*0104 (19.93% vs. 9.40%, Pc < 1 x 10(-3)), -DQA1*0201 (22.40% vs. 10.74%, Pc
      < 1 x 10(-3)), -DQB1*0303 (18.12% vs. 9.73%, Pc < 1 x 10(-7)), and -DRB1*0701/02
      (26.09% vs. 9.73%, Pc < 1 x 10(-7)) were significantly increased in PV patients,
      while HLA-B*57, -DQB1*0201 were slightly increased in PV patients. HLA-Cw*0304
      (5.07% vs. 14.43%, Pc < 1 x 10(-3)), -DQA1*0501 (5.79% vs. 14.09%, Pc < 0.05)
      were found to be negatively associated with PV, but HLA-A*2 (2.54% vs. 6.38%, Pc
      < 0.5) was decreased in PV patients without statistical significance. (ii) HLA
      A*26-B*27 [P < 0.0001, odds ratio (OR) = 48.38], -A*26-Cw*0602 (P < 0.0001, OR =
      11.84), -B*27-Cw*0602 (P < 0.0001, OR = undefined), -DRB1*0701/02-B*27 (P <
      0.0001, OR = 22.62), -DRB1*0701/02-DQA1*0104 (P < 0.0002, OR = 3.59), 
      DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 5.63), -DQA1*0201-DQB1*0303 (P < 0.0002,
      OR = 7.77), -A*26-B*27-Cw*0602 (P < 0.0004, OR = undefined), -A*26-DRB1*0701/02
      DQA1*0201-DQB1*0303 (P < 0.01, OR = undefined) were identified as risk haplotypes
      for patients with PV in China. (iii) HLA-A*26 -B*27 (P < 0.0001, OR = 58.47), 
      DQA1*0201-DQB1*0303 (P < 0.0001, OR = 8.62), -DRB1*0701/02 -DQA1*0104 (P <
      0.0002, OR = 4.13), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 6.68) and -A*26
      DRB1*0701-DQA1*0201 -DQB1*0303 (P < 0.006, OR = undefined) were only
      significantly associated with type I psoriasis compared with controls, while
      others showed no differences in either type I or type II psoriasis. (iv) These
      associated haplotypes with PV were not different by sex, except that the
      frequency of DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 10.14) was higher in male
      patients with psoriasis. To summarize, this study demonstrated a differential
      association of HLA and identified some special risk haplotypes in Chinese
      patients with PV compared with other ethnic or racial populations.

PMID- 15245542
TI  - Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo.
AB  - Vitiligo is a common pigmentary disorder of the skin with selective destruction
      of melanocytes. The pathogenetic mechanisms in vitiligo have not been completely
      clarified. The aim of our investigation was to evaluate the oxidative stress in
      the pathogenesis of generalized vitiligo. Twenty-seven patients with generalized
      vitiligo and 24 phototype-, age-, and sex-matched healthy controls were included
      in this study. We analysed serum levels of malondialdehyde (MDA), nitric oxide
      (NO), and serum activities of superoxide dismutase (SOD) and xanthine oxidase
      (XO) in the patients with vitiligo and in the controls. We found significantly
      higher levels of MDA and XO activity (P < 0.001 and P < 0.05, respectively), and
      a significantly lower level of serum SOD activity (P < 0.05) in patients with
      vitiligo compared with the controls. However, the increase in the level of serum
      NO was insignificant (P > 0.05). These results suggest that lipid peroxidation of
      cellular membrane of melanocytes by free radicals may have a significant role in
      the pathogenesis of generalized vitiligo.

PMID- 15245543
TI  - Improvement of adult Still's disease with granulocyte and monocyte adsorption
      apheresis.
AB  - Adult Still's disease is characterized by a high spiking fever, transient skin
      rash, and polyarthralgia. Joint pain is one of the major complaints and is often
      intractable. We assessed the efficacy of granulocyte and monocyte adsorption
      apheresis (GCAP) therapy for treating arthralgia in adult Still's disease. A 33
      year-old woman with adult Still's disease who suffered from recalcitrant
      arthralgia resistant to systemic corticosteroids was treated with GCAP therapy.
      She underwent five GCAP treatments at 5-day intervals. Her joint pain responded
      dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating
      adult Still's disease. We present a detailed description of the patient and this
      novel therapy.

PMID- 15245544
TI  - History of psoriasis response to sunlight does not predict outcome of UVB
      phototherapy.
AB  - We prospectively asked 146 consecutive patients starting narrow-band UVB (NB-UVB)
      for psoriasis about the effects of sunlight on their psoriasis. Eighty-eight
      (60%) patients reported improvement with sunlight, six (4%) reported worsening,
      and 52 (36%) had not noted any change in their psoriasis with sunlight exposure.
      Overall, 101 (69%) were recorded to reach clearance or minimal residual activity
      (MRA), 24 (16.5%) to achieve moderate improvement, and 21 (14.5%) had other
      recorded outcomes (mainly 'did not attend'), with UVB phototherapy. Forty-two
      (72%) of the 58 who did not report improvement with sunlight went on to
      clearance/MRA with UVB compared to 59/88 (67%) of those who did report
      improvement (95% confidence interval for difference in percentage improving, -10%
      to 20%, P = 0.49). Patients' replies to questions about how their psoriasis
      responds to sunlight do not appear to predict response to UVB phototherapy in our
      patient population.

PMID- 15245545
TI  - Is slow nail growth a risk factor for onychomycosis?
AB  - This study was carried out to determine whether slow nail growth is a
      predisposing factor for onychomycosis or if onychomycosis results in slow nail
      growth. Forty-nine patients with unilateral onychomycosis of the great toenail
      were enrolled and classified in two groups according to the size of affected
      area, i.e. more than half or less than half of the toenail. The growth rates of
      affected and unaffected great toenails of all patients were measured. Before a
      normal appearance was reached, the growth rates of affected great toenails, when
      the affected area occupied more than half of total nail plate, was slower than
      that of the unaffected great toenails. After a normal appearance was achieved,
      there were no differences in growth rates between affected and unaffected great
      toenails. Therefore, this study of patients with unilateral toenail onychomycosis
      did not support the hypothesis that slow nail growth rate is a predisposing
      factor for onychomycosis.

PMID- 15245546
TI  - Topical provocation in fixed drug eruption due to metamizol and naproxen.
AB  - The aim of this study was to investigate the usefulness of topical provocation in
      the diagnosis of metamizol- and naproxen-induced fixed drug eruption (FDE). Five
      patients with metamizol- and four patients with naproxen-induced FDE established
      by oral provocation were tested with the causative drugs at concentrations of
      10%, 20%, and 50% in white petrolatum both on previously involved and uninvolved
      skin using the occlusive patch test technique. Additionally, four patients with
      metamizol- and five patients with naproxen-induced FDE, and 20 healthy controls
      were tested openly with drug preparations in dimethyl sulfoxide (DMSO). Tape
      stripping occlusive patch testing in petrolatum remained negative in all. Open
      testing with drug preparations in DMSO revealed positive results in all four
      patients tested with metamizol mainly at concentrations of 20%, and in three of
      five patients tested with naproxen exclusively at concentrations of 50%. No
      positive reaction was seen on previously uninvolved skin and in healthy controls
      with any drug concentration and pure DMSO. In conclusion, repeated open testing
      with concentrations of the drugs up to 50% in DMSO seems to be a reliable test
      method in metamizol-induced FDE whereas oral provocation is still the most
      reliable method for naproxen-induced FDE as false negative results were common
      when testing topically with naproxen.

PMID- 15245547
TI  - Mycobacterium chelonae I infection mimicking acne conglobata in an
      immunocompetent host.

PMID- 15245548
TI  - Changing pattern of drug-induced toxic epidermal necrolysis in developing
      countries.

PMID- 15245549
TI  - Erythema nodosum associated with carcinoid tumour.

PMID- 15245550
TI  - Acute lipodermatosclerosis in a 15-year-old girl?

PMID- 15245551
TI  - Acrokeratosis paraneoplastica (Bazex syndrome) associated with breast cancer.

PMID- 15245552
TI  - Acrokeratosis paraneoplastica associated with recurrent metastatic thymic
      carcinoma.

PMID- 15245553
TI  - Yellow nail syndrome and lung lymphoma.

PMID- 15245554
TI  - Van der Woude syndrome.

PMID- 15245555
TI  - Psoriasis vulgaris confined to vitiligo patches and occurring contemporaneously
      in the same patient.

PMID- 15245556
TI  - Naevoid hypertrichosis treated with alexandrite laser.

PMID- 15245557
TI  - Case 1.

PMID- 15245558
TI  - Case 2.

PMID- 15245559
TI  - Assessment in undergraduate dermatology.
AB  - Assessment should be considered at an early stage in curriculum planning and must
      strive for the best balance between validity (testing what is important) and
      reliability (providing inferences about the student's competence). The primary
      purpose of summative assessment in clinical medicine is to determine whether the
      candidate is competent. Dermatologists should use a range of summative assessment
      techniques that are appropriate for testing the curricular outcomes. These will
      include tests of application of knowledge and of clinical skills. All students
      should also receive regular formative assessment to allow them to measure their
      progress, but this is not used for summative decisions. We review the key issues
      surrounding assessment and some specific techniques that might be appropriate for
      testing learning outcomes in undergraduate dermatology, either in the context of
      a clinical placement or in an integrated assessment involving a number of
      specialties or systems.

PMID- 15245563
TI  - Primary rat muscle progenitor cells have decreased proliferation and myotube
      formation during passages.
AB  - Adult skeletal muscle contains populations of satellite cells and muscle-derived
      stem cells that are capable of forming multinucleate myotubes. The purpose of
      this study was to determine the phenotype of cells isolated from a common
      satellite cell isolation and passaging procedure from whole skeletal muscle. To
      ascertain the characteristics of the cellular phenotype, the myogenic markers
      MyoD and desmin, the satellite-cell-specific marker Pax7, and the haemopoietic
      stem cell markers CD34 and CD45 were examined by immunohistochemical analysis.
      Immediately after isolation, > 90% myogenic marker-positive cells were positive
      for desmin, MyoD and Pax7. In contrast, approximately 10% of the isolated cells
      expressed only CD34 or CD45. After three passages, the percentage of cells that
      were positive for the myogenic markers desmin, MyoD and Pax7 was reduced to
      approximately 55%, while the population of CD34- or CD45-positive cells increased
      to approximately 30% after the third passage. Immunohistochemical detection of
      bromodeoxyuridine demonstrated that the number of proliferating cells decreased
      progressively after each passaging. Finally, after the third passage the
      percentage of nuclei in myotubes decreased from 46.7% to 12.5%. Since passaging
      of muscle progenitor cells is common practice, the results of the current report
      suggest that characterization of cell heterogeneity needs to be made frequently.

PMID- 15245564
TI  - A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization
      into the peripheral blood.
AB  - A mathematical model for the kinetics of haemopoietic cells, including
      CD34+cells, is proposed. This minimal model reflects the known kinetics of
      haemopoietic progenitor cells, including peripheral blood CD34+ cells, white
      blood cells and platelets, in the presence of granulocyte colony-stimulating
      factor. Reproducing known perturbations within this system, subjected to
      granulocyte colony-stimulating factor treatment and apheresis of peripheral blood
      progenitor cells (CD34+ cells) in healthy individuals allows validation of the
      model. Predictions are made with this model for reducing the length of time with
      neutropenia after high-dose chemotherapy. Results based on this model indicate
      that myelosuppressive treatment together with infusion of CD34+ peripheral blood
      progenitor cells favours a faster recovery of the haemopoietic system than with
      granulocyte colony-stimulating factor alone. Additionally, it predicts that
      infusion of white blood cells and platelets can relieve the symptoms of
      neutropenia and thrombocytopenia, respectively, without drastically hindering the
      haemopoietic recovery period after high dose chemotherapy.

PMID- 15245565
TI  - Thrombopoietin, flt3-ligand and c-kit-ligand modulate HOX gene expression in
      expanding cord blood CD133 cells.
AB  - Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic
      and intrinsic stimuli. Extrinsic modulators include growth factors and cell
      adhesion molecules, whereas intrinsic regulation is achieved with many
      transcription factor families, of which the HOX gene products are known to be
      important in haemopoiesis. Umbilical cord blood CD133+ HSPC proliferation
      potential was tested in liquid culture with 'TPOFLK' (thrombopoietin, flt-3
      ligand and c-kit ligand, promoting HSPC survival and self-renewal), in comparison
      to 'K36EG' (c-kit-ligand, interleukins-3 and -6, erythropoietin and granulocyte
      colony-stimulating factor, inducing haemopoietic differentiation). TPOFLK induced
      a higher CD133+ HSPC proliferation (up to 60-fold more, at week 8) and maintained
      a higher frequency of the primitive colony-forming cells than K36EG. Quantitative
      polymerase chain reaction analysis revealed opposite expression patterns for
      specific HOX genes in expanding cord blood CD133+ HSPC. After 8 weeks in liquid
      culture, TPOFLK increased the expression of HOX B3, B4 and A9 (associated with
      uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in
      committed myeloid cells) when compared to K36EG. These results suggest that
      TPOFLK induces CD133+ HSPC proliferation, self-renewal and maintenance, up
      regulation of HOX B3, B4 and A9 and down-regulation of HOX B8 and A10 gene
      expression.

PMID- 15245566
TI  - Insulin reduces apoptosis and increases DNA synthesis and cell size via distinct
      signalling pathways in Drosophila Kc cells.
AB  - During development of Drosophila, cell proliferation and size are known to be
      regulated by insulin. Here we use Drosophila Kc cells to examine the molecular
      basis for the control of cell growth by insulin. Growing cells in the presence of
      insulin increased cell number above control levels at 16, 24, 48 and 72 h. We
      have demonstrated a novel anti-apoptotic effect of insulin (approximately 50%) in
      these cells, measured by caspase 3-like activity, which contributed to the
      increase in cell number. The anti-apoptotic effect was observed both in control
      cells and those in which apoptosis was induced by ultraviolet irradiation. An
      approximately 2-fold stimulation of bromodeoxyuridine incorporation demonstrated
      that insulin also increased Kc cell proliferation by stimulating new DNA
      synthesis. The ability of insulin to increase cell number, stimulate
      bromodeoxyuridine incorporation and reduce caspase 3-like activity was prevented
      by PD98059, which inhibits activation of the Drosophila extracellular signal
      regulated kinase (DERK) pathway, and was unaffected by wortmannin, an inhibitor
      of Drosophila phosphatidylinositol 3-kinase (DPI3K). Insulin also increased cell
      size approximately 2-fold and this was prevented by wortmannin and rapamycin, an
      inhibitor of Drosphilia target of rapamycin (DTOR). In summary, we show that DERK
      plays an important role in mediating the effect of insulin to reduce apoptosis
      and increase DNA synthesis whereas the DPI3K/DTOR/Dp70S6 kinase pathway mediates
      effects of insulin on cell size in Drosophila Kc cells.

PMID- 15245567
TI  - Telomere attrition and accumulation of senescent cells in cultured human
      endothelial cells.
AB  - The human umbilical vein endothelial cell (HUVEC) is an important model of the
      human endothelium that is widely used in vascular research. HUVECs and the adult
      endothelium share many characteristics including progression into senescence as
      the cells age. Despite this, the shortening of telomeres and its relationship to
      the progression into senescence are poorly defined in HUVECs. In this study of
      several HUVEC lines we show notable consistency in their growth curves. There is
      a steady decline in the growth rate of HUVECs grown continually in culture and we
      estimate complete cessation of growth after approximately 70 population
      doublings. The HUVECs lose telomeric DNA at a consistent rate of 90 base
      pairs/population doubling and show a progressive accumulation of shortened
      telomeres (below 5 kilobases). This telomeric loss correlates with the
      accumulation of senescent HUVECs in culture as assessed by staining for beta
      galactosidase activity at pH 6. Although the telomere length of a large
      population of cells is a relatively crude measure, we suggest that in HUVECs a
      mean telomere length (as measured by terminal restriction fragment length) of 5
      kilobases is associated with entry into senescence. These data demonstrate the
      strong relationship between telomere attrition and cell senescence in HUVECs.
      They suggest that DNA damage and subsequent telomere attrition are likely to be
      key mechanisms driving the development of endothelial senescence in the
      pathogenesis of vascular disease.

PMID- 15245568
TI  - Dose of proton pump inhibitors and the CYP2C19 genotype.

PMID- 15245569
TI  - CYP2C19 polymorphism and proton pump inhibitors.
AB  - Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole,
      pantoprazole and rabeprazole are eliminated by the hepatic route and the
      polymorphic CYP2C19 is mainly involved in their metabolism. In different
      populations three phenotypes have been identified: extensive metabolizers, poor
      metabolizers and individuals carrying one wild type and one mutant allele (het
      extensive metabolizers). Systemic exposure to the proton pump inhibitors as
      expressed by the AUC (area under the plasma level time profiles) is 5-12-times
      higher in poor metabolizers than in extensive metabolizers. As the
      pharmacodynamic response (elevation of intragastric pH) to the proton pump
      inhibitors is related directly to their AUC, a much higher pH can be monitored
      over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore,
      clinical efficacy of all proton pump inhibitors depend on maintaining
      intragastric pH above certain threshold levels and significantly higher
      eradication rates of Helicobacter pylori have been observed in patients of the
      poor metabolizers and het extensive metabolizers phenotype if compared to
      extensive metabolizers. Likewise, limited data suggest that proton pump
      inhibitors-induced healing rates in gastro-oesophageal reflux disease are
      apparently higher in poor metabolizers/het extensive metabolizers than in
      extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme
      and higher dosage in extensive metabolizers is likely to improve the clinical
      efficacy of proton pump inhibitors.

PMID- 15245570
TI  - Cellular mechanisms of atracurium-induced tetanic fade in the isolated rat
      muscle.
AB  - Although atracurium is a widely used neuromuscular blocker, we still lack
      knowledge regarding some of its cellular mechanisms of action. Thus, similar to
      other clinically used blockers atracurium induces, both in vivo and in vitro,
      fade of the tetanic contraction. However, the cellular mechanisms underlying this
      tetanic fade have never been systematically studied. In the present work these
      mechanisms were investigated in vitro. A sciatic nerve extensor digitorum longus
      muscle preparation of the rat was used. A combination of myographical and
      electrophysiological techniques was employed. Indirect twitches were evoked at
      0.1 Hz and tetanic contractions at 50 Hz. Trains of end-plate potentials were
      evoked at a frequency of 50 Hz. The electrophysiological variables used in the
      analysis of the trains of end-plate potentials were: peak amplitude of the first
      end-plate potential in the train, peak amplitude of plateau end-plate potentials
      in the train, tetanic run-down of the end-plate potentials' train, quantal
      content of first and plateau end-plate potentials in the train, quantal size. In
      the myographical study atracurium, at a concentration of 2.4 microM, induced a
      complete fade of the tetanic contraction while only slightly affected the twitch.
      In the electrophysiological study atracurium, at the same 2.4 microM
      concentration, significantly decreased the amplitude of both first end-plate
      potentials in the train (control: 14.4 mV; atracurium: 3.2 mV) and plateau end
      plate potentials (control: 10.8 mV; atracurium: 2.4 mV) and reinforced the
      tetanic run-down of the train of end-plate potentials, evaluated as the percent
      loss in amplitude of plateau end-plate potentials compared to first end-plate
      potentials in the trains (control: 25.2%; atracurium: 33.2%). Atracurium also
      significantly decreased the quantal content of first end-plate potentials in the
      train (control: 231; atracurium: 68), the quantal content of plateau end-plate
      potentials (control: 159; atracurium: 42) and the quantal size (control: 0.119
      mV; atracurium: 0.075 mV). In relative terms the decrease in quantal content was
      about twice as large as the decrease in quantal size. This indicates that the
      fade of the tetanic contraction induced by atracurium (2.4 microM) is due to both
      pre- and postsynaptic blocking effects, the presynaptic one being stronger.

PMID- 15245571
TI  - Aspirin attenuates the initiation but not the progression of atherosclerosis in
      apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet.
AB  - Aspirin has potent antiinflammatory properties and attenuates atherosclerosis in
      apolipoprotein-E-deficient mice fed a high-fat, high-cholesterol diet. In an
      attempt to clarify the contradictory results obtained with normal chow, we
      studied the effect of aspirin for a prolonged period of time. The mice were fed a
      commercial chow until the experiment began at 8 weeks of age. Blood samples were
      then obtained and several mice (n=8) were sacrificed. The diet of the remaining
      48 animals was supplemented with 200 g/kg palm fat and 1 g/kg cholesterol. They
      were then randomly divided into 2 groups, one of which received 0.5 mg/day of
      aspirin. The aspirin had a time-dependent effect. First, the extent of lesion
      decreased; then the effect was neutral; and, finally, after longer periods of
      being fed the atherogenic diet and receiving aspirin, the extent of the lesion
      increased. The transitory effect of aspirin should be elucidated in the absence
      of high dietary lipids.

PMID- 15245572
TI  - Influence of spironolactone treatment on gentamicin-induced nephrotoxicity in
      rats.
AB  - The effect of treatment of rats with gentamicin (80 mg/kg/day for 6 days), oral
      doses of spironolacatone (20 mg/kg/day for 6 days), and the combined treatment
      (spironolactone + gentamicin) on renal histology and reduced glutathione (GSH)
      concentration, and some serum constituents indicative of kidney function were
      studied. The serum concentrations of creatinine and urea were not significantly
      affected by spironolactone treatment, but were significantly elevated (P<0.05) by
      gentamicin administration. The antibiotic treatment also reduced GSH
      concentration and caused a moderate renal cortical necrosis. However, rats
      exposed to spironolactone + gentamicin revealed drastic increases in the serum
      urea and creatinine concentrations amounting to about 1.8 and 2.1 times those of
      rats treated with gentamicin alone, respectively. The histological examination of
      slides of the renal cortex of rats exposed to the combined drugs exhibited more
      extensive necrosis in the tubules when compared to those treated with gentamicin
      alone. The reduction in GSH induced by gentamicin was unaffected by the
      concomitant treatment of gentamicin and spironolactone. The concentration of
      gentamicin accumulated in the renal cortex was significantly larger (twofold) in
      rats treated concomitantly with spironolactone + gentamicin than in rats treated
      with gentamicin alone. The present results indicate that spironolactone
      aggravates gentamicin-induced nephrotoxicity in the rat.

PMID- 15245573
TI  - Effects of acute and chronic treatment with the sodium hydrogen exchanger 1 (NHE
      1) inhibitor cariporide on myocardial infarct mass in rabbits with
      hypercholesterolaemia.
AB  - We investigated the cardioprotective effect of acute and chronic sodium hydrogen
      exchanger 1 (NHE-1) inhibition with cariporide under pathological conditions in
      rabbits fed an atherogenic diet (0.25% cholesterol, 3% coconut oil), an
      experimental model of atherosclerosis. New Zealand White rabbits were fed over 4
      weeks with normal diet or with atherogenic diet and randomized in 3 subgroups
      (n=7 in each group); placebo, acute cariporide (0.3 mg/kg, 10 min. before
      occlusion of left anterior descending coronary artery and chronic cariporide (4
      weeks 0.1% in chow). In the final infarction experiments the animals were
      subjected to 30 min. of myocardial ischaemia by occlusion of a branch of the left
      anterior descending coronary artery followed by 2 hr of reperfusion. Infarct mass
      was evaluated by triphenyl-tetrazolium chloride staining and the infarct size
      expressed as a percentage of area at risk. Besides the assessment of aortic
      endothelium-dependent function aortic and cardiac vessels were inspected for
      atherosclerotic lesions. In cholesterol-fed rabbits, the infarct size was
      significantly increased when compared with normal diet animals (63+/-3% versus
      41+/-3%). Acute cariporide treatment reduced the infarct size in normal diet
      rabbits to 14%+/-3% (66% decrease, P<0.05) as well as in atherogenic diet rabbits
      to 22+/-3% (65% decrease, P<0.05). Chronic treatment with cariporide also reduced
      the infarct size significantly: normal diet 19+/-2% (53% decrease, P<0.05),
      atherogenic diet 32+/-3% (49% decrease, P<0.05). Total cholesterol serum levels
      in rabbits with atherogenic diet were significantly higher (15.3+/-2.7 mmol/l)
      than those on a standard diet (0.65+/-0.08 mmol/l). Chronic cariporide treatment
      significantly attenuated the increase of serum cholesterol (7.9+/-1.9 mmol/l) and
      improved the lipoprotein pattern. Although the aortas and heart vessels of
      hypercholesterolaemic animals were without any histological evidence of
      atherosclerosis they developed endothelial dysfunction (reduced endothelium
      dependent relaxation by ACh), which was prevented by chronic cariporide
      treatment. Acute and chronic treatment with the NHE-1 inhibitor cariporide
      significantly reduced infarct mass. This effect was associated with improved
      endothelial function.

PMID- 15245574
TI  - Comparison of patient questionnaires and plasma assays in intentional drug
      overdoses.
AB  - Our aim was to explore the agreement between clinically collected information on
      purported drug intake and plasma data in intentional drug overdose. We included
      all subjects with intentional drug overdose above 15 years of age consecutively
      admitted to the Emergency Department of the University Hospital during 4 months.
      Information about drugs used and sources of this information was collected and
      compared to presence of drug in plasma, concerning four drugs with high toxic
      potential (tricyclic antidepressants, meprobamate, paracetamol and ethanol).
      Sensitivity, specificity, predictive positive and negative values of all sources
      of information pooled were assessed for each drug. 413 intentional drug overdoses
      were included, 66% with more than one drug. According to clinical information, 8%
      took tricyclic antidepressants, 11% meprobamate, 9% paracetamol and 41% ethanol.
      Systematic plasma assays confirmed this in 59% of cases for tricyclic
      antidepressants, 76% for meprobamate and ethanol, and 77% for paracetamol. Plasma
      concentrations were considered toxic in 28% of cases for tricyclic
      antidepressants, 65% for meprobamate, 43% for ethanol and never for paracetamol.
      Tricyclic antidepressants and meprobamate were found unexpectedly in 3%,
      paracetamol in 7% and ethanol in 6%. Toxic concentrations were found only with
      meprobamate. The risk of erroneous, clinically collected information was greater
      by excess (25 to 40% false positives) than by lack (3 to 7% false negatives).
      Thus, the consequences of erroneous, clinically collected information were
      probably more excess cost for the institution than medical risk for the patients.
      However these results found at the population level may not be true at an
      individual level.

PMID- 15245575
TI  - Human skeletal muscle lactate dehydrogenase activity in the presence of some
      alcohol dehydrogenase inhibitors.
AB  - Methanol, ethylene glycol and other alcohol intoxications are complicated by
      severe acidosis which could be caused by formation of metabolic acids and
      additionally lactic acid production. An increasing nicotinamide adenine
      dinucleotide reduced/nicotinamide adenine dinucleotide oxidized (NADH/NAD) ratio
      during alcohol biotransformation is responsible for the induction of lactic
      acidosis. The main purpose of the present paper was to evaluate the effect of 4
      methylpyrazole, cimetidine, ethylenediaminetetraacetic acid disodium salt,
      ethanol and methanol on lactate dehydrogenase (E.C. 1.1.1.27) activity and to
      discuss this issue. The activity of the enzyme was determined
      spectrophotometrically, in vitro using human enzyme skeletal muscle homogenates.
      4-Methylpyrazole, cimetidine and ethylenediaminetetraacetic acid disodium salt at
      concentrations 0.01, 0.1, 1.0 mM and 12.5, 25.0, 50.0 mM of ethanol and methanol
      were studied. Our results showed that cimetidine increased lactate dehydrogenase
      activity as compared to the control at all tested concentrations. Such activity
      was noted for 4-methylpyrazole at 0.1 mM and higher concentration. By contrast,
      no significant effect on lactate dehydrogenase activity in the presence of
      ethylenediaminetetraacetic acid disodium salt, methanol and ethanol was observed.

PMID- 15245576
TI  - Up-regulation of endothelin receptor function and mRNA expression in airway
      smooth muscle cells following Sephadex-induced airway inflammation.
AB  - The hypothesis that up-regulation of bronchial constrictor endothelin receptors
      in airway smooth muscle cells may contribute to hyperreactivity during airway
      inflammation was tested in the present study by quantitative endothelin receptor
      mRNA analysis and functional responses in ring segments of rat trachea and
      bronchi. Real time reverse transcription polymerase chain reaction was used to
      quantify endothelin receptor expression in rat airway smooth muscle cells
      following Sephadex-induced inflammation. Compared with controls, Sephadex-induced
      airway inflammation caused a significant increase (3.9 times P<0.05) of
      endothelin receptor type B mRNA expression in bronchial smooth muscle cells, but
      not in tracheal smooth muscle cells. Functional myograph studies of bronchial and
      tracheal ring segments without epithelium (mechanically denuded) revealed an
      increase of the maximum contractile effects of endothelin-1 (a dual agonist for
      both endothelin type A and B receptors) and sarafotoxin 6c (a selective agonist
      for endothelin B receptors) in bronchial smooth muscle cells in Sephadex-induced
      inflammation, but not in tracheal smooth muscle cells. The enhanced maximal
      responses of bronchial smooth muscle cells to endothelin-1 and sarafotoxin 6c in
      Sephadex-induced inflammation support our molecular findings and hence imply a
      role for endothelin B receptors in airway hyperreactivity during airway
      inflammation.

PMID- 15245578
TI  - Sources of evidence in HIV/AIDS care: pilot study comparing family physicians and
      AIDS service organization staff.
AB  - BACKGROUND: The improvement of the quality of the evidence used in treatment
      decision-making is especially important in the case of patients with complicated
      disease processes such as HIV/AIDS for which multiple treatment strategies exist
      with conflicting reports of efficacy. Little is known about the perceptions of
      distinct groups of health care workers regarding various sources of evidence and
      how these influence the clinical decision-making process. Our objective was to
      investigate how two groups of treatment information providers for people living
      with HIV/AIDS perceive the importance of various sources of treatment
      information. METHODS: Surveys were distributed to staff at two local AIDS service
      organizations and to family physicians at three community health centres treating
      people living with HIV/AIDS. Participants were asked to rate the importance of 10
      different sources of evidence for HIV/AIDS treatment information on a 5-point
      Likert-type scale. Mean rating scores and relative rankings were compared.
      RESULTS: Findings suggest that a discordance exists between the two health
      information provider groups in terms of their perceptions of the various sources
      of evidence. Furthermore, AIDS service organization staff ranked health care
      professionals as the most important source of information whereas physicians
      deemed AIDS service organizations to be relatively unimportant. The two groups
      appear to share a common mistrust for information from pharmaceutical industries.
      CONCLUSIONS: Discordance exists between medical "experts" from different
      backgrounds relating to their perceptions of evidence. Further investigation is
      warranted in order to reveal any effects on the quality of treatment information
      and implications in the decision-making process. Possible effects on
      collaboration and working relationships also warrant further exploration.

PMID- 15245577
TI  - Antioxidant defense in Plasmodium falciparum--data mining of the transcriptome.
AB  - The intraerythrocytic malaria parasite is under constant oxidative stress
      originating both from endogenous and exogenous processes. The parasite is endowed
      with a complete network of enzymes and proteins that protect it from those
      threats, but also uses redox activities to regulate enzyme activities. In the
      present analysis, the transcription of the genes coding for the antioxidant
      defense elements are viewed in the time-frame of the intraerythrocytic cycle.
      Time-dependent transcription data were taken from the transcriptome of the human
      malaria parasite Plasmodium falciparum. Whereas for several processes the
      transcription of the many participating genes is coordinated, in the present case
      there are some outstanding deviations where gene products that utilize
      glutathione or thioredoxin are transcribed before the genes coding for elements
      that control the levels of those substrates are transcribed. Such insights may
      hint to novel, non-classical pathways that necessitate further investigations.

PMID- 15245579
TI  - Clinical utility of antinuclear antibody tests in children.
AB  - BACKGROUND: Antinuclear antibody (ANA) tests are frequently used to screen
      children for chronic inflammatory diseases such as systemic lupus erythematosus
      (SLE). However, the diagnostic utility of this test is limited because of the
      large number of healthy children who have low-titer positive tests. We sought to
      determine the clinical utility of ANA tests in screening children for rheumatic
      disease and to determine whether there are specific signs or symptoms that
      enhance the clinical utility of ANA tests in children. METHODS: We undertook a
      retrospective analysis of 509 new patient referrals. Charts of patients referred
      because of results of ANA testing were selected for further analysis. Children
      with JRA, SLE, and other conditions were compared using demographic data, chief
      complaints at the time of presentation, and ANA titers. RESULTS: One hundred ten
      patients were referred because of an ANA test interpreted as positive. Ten
      patients were subsequently diagnosed with SLE. In addition, we identified one
      patient with mixed connective tissue disease, and an additional child with
      idiopathic Raynaud's phenomenon. Eighteen children of the children referred for a
      positive ANA test had juvenile rheumatoid arthritis (JRA). Another 80 children
      with positive ANA tests were identified, the majority of whom (n = 39, 49%) had
      musculoskeletal pain syndromes. Neither the presence nor the titer of ANA served
      to distinguish children with JRA from children with other musculoskeletal
      conditions. Children with JRA were readily identified on the basis of the history
      and physical examination. Children with SLE were therefore compared with children
      with positive ANA tests who did not have JRA, designated the "comparison group."
      Non-urticarial rash was more common in children with SLE than in children without
      chronic inflammatory disease (p = 0.007). Children with SLE were also older (mean
      +/- sd = 14.2 +/- 2.5 years) than the comparison group (11.0 +/- 3.6 years; p =
      0.001). ANA titer was also a significant discriminator between children with SLE
      and children without chronic inflammatory disease. The median ANA titer in
      children with SLE was 1: 1,080 compared with 1:160 for other children (p <
      0.0001). ANA titers of >/=1,080 had a positive predictive value for SLE of 1.0
      while titers of </=1: 360 had a negative predictive value for lupus of 0.84.
      CONCLUSION: Age and ANA titer assist in discriminating children with SLE from
      children with other conditions. ANA tests are of no diagnostic utility in either
      making or excluding the diagnosis of JRA.

PMID- 15245580
TI  - Phase II study of neoadjuvant 5-FU + leucovorin + CPT-11 in patients with
      resectable liver metastases from colorectal adenocarcinoma.
AB  - BACKGROUND: Following resection of liver metastases from colorectal cancer, 5
      year survivals are reportedly 30 - 39%. It can be assumed that this clinical
      situation represents systemic disease. Therefore, it is postulated that systemic
      chemotherapy would improve outcomes, particularly in those whose disease is
      sensitive to the agents administered. One potential advantage of neoadjuvant
      chemotherapy is that it provides in vivo chemosensitivity data. Response to
      neoadjuvant chemotherapy could therefore guide adjuvant chemotherapy following
      resection of liver metastases from colorectal cancer. METHODS AND DESIGN: This is
      a prospective Phase II evaluation of outcomes in patients with potentially
      resectable liver metastases. Patients will receive neoadjuvant chemotherapy and
      will undergo resection. Postoperative chemotherapy will be directed by the degree
      of response to preoperative chemotherapy. All patients with Stage IV colorectal
      adenocarcinoma isolated to the liver that have disease that is amenable to
      complete ablation by resection, radiofrequency ablation, and/or cryoablation will
      be candidates for the trial. Patients will receive CPT-11 180 mg/m2 IV (over 90
      minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and
      calcium folinate 200 mg/m2 on days 1 and 2, every 2 weeks. Altogether, six cycles
      of chemotherapy will be administered. Patients will then undergo resection and/or
      radiofrequency ablation. Patients who had stable disease or a clinical response
      with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180
      mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22
      hour infusion and calcium folinate 200 mg/m2 on days 1 and 2 (given every 2
      weeks). Patients with resectable disease who had progressive disease during
      neoadjuvant chemotherapy will receive best supportive care or an alternative
      agent, at the discretion of the treating physician. Those patients who are not
      rendered free of disease following the neoadjuvant chemotherapy and surgery will
      receive best supportive care or an alternative agent, at the discretion of the
      treating physician. The primary endpoint of the study is disease-free survival.
      Secondary endpoints include overall survival, safety and feasibility, response to
      chemotherapy, and quality of life.

PMID- 15245581
TI  - Is the gene encoding Chibby implicated as a tumour suppressor in colorectal
      cancer ?
AB  - BACKGROUND: A novel member of the Wnt signalling pathway, Chibby, was recently
      identified. This protein inhibits Wnt/beta-catenin mediated transcriptional
      activation by competing with Lef-1 (the transcription factor and target of beta
      catenin) to bind to beta-catenin. This suggests that Chibby could be a tumour
      suppressor protein. The C22orf2 gene coding Chibby is located on chromosome 22, a
      region recurrently lost in colorectal cancer. Activation of the Wnt pathway is a
      major feature of colorectal cancer and occurs through inactivation of APC or
      activation of beta-catenin. All of this led us to analyse the possible
      implication of Chibby in colorectal carcinogenesis. METHODS: First, 36 tumour and
      matched normal colonic mucosa DNA were genotyped with five microsatellite markers
      located on chromosome 22 to search for loss of heterozygosity. Then, mutation
      screening of the C22orf2 coding sequence and splice sites was performed in the 36
      tumour DNA. Finally, expression of Chibby was analysed by quantitative RT-PCR on
      10 patients, 4 with loss of heterozygosity (LOH) on chromosome 22. RESULTS: Loss
      of heterozygosity involving the C22orf2 region was detected in 11 out of 36
      patients (30%). Sequencing analysis revealed a known variant, rs3747174, in exon
      5: T321C leading to a silent amino acid polymorphism A107A. Allelic frequencies
      were 0.69 and 0.31 for T and C variants respectively. No other mutation was
      detected. Among the 10 patients studied, expression analysis revealed that Chibby
      is overexpressed in 2 tumours and underexpressed in 1. No correlations were found
      with 22q LOH status. CONCLUSION: As no somatic mutation was detected in C22orf2
      in 36 colorectal tumour DNA, our results do not support the implication of Chibby
      as a tumour suppressor in colorectal carcinogenesis. This was supported by the
      absence of underexpression of Chibby among the tumour samples with 22q LOH. The
      implication of other Wnt pathway members remains to be identified to explain the
      part of colorectal tumours without mutation in APC and beta-catenin.

PMID- 15245582
TI  - Infection-dependent phenotypes in MHC-congenic mice are not due to MHC: can we
      trust congenic animals?
AB  - BACKGROUND: Congenic strains of mice are assumed to differ only at a single gene
      or region of the genome. These mice have great importance in evaluating the
      function of genes. However, their utility depends on the maintenance of this true
      congenic nature. Although, accumulating evidence suggests that congenic strains
      suffer genetic divergence that could compromise interpretation of experimental
      results, this problem is usually ignored. During coinfection studies with
      Salmonella typhimurium and Theiler's murine encephalomyelitis virus (TMEV) in
      major histocompatibility complex (MHC)-congenic mice, we conducted the proper F2
      controls and discovered significant differences between these F2 animals and MHC
      genotype-matched P0 and F1 animals in weight gain and pathogen load. To
      systematically evaluate the apparent non-MHC differences in these mice, we
      infected all three generations (P0, F1 and F2) for 5 MHC genotypes (b/b, b/q and
      q/q as well as d/d, d/q, and q/q) with Salmonella and TMEV. RESULTS: Infected P0
      MHC q/q congenic homozygotes lost significantly more weight (p = 0.02) and had
      significantly higher Salmonella (p < 0.01) and TMEV (p = 0.02) titers than the
      infected F2 q/q homozygotes. Neither weight nor pathogen load differences were
      present in sham-infected controls. CONCLUSIONS: These data suggest that these
      strains differ for genes other than those in the MHC congenic region. The most
      likely explanation is that deleterious recessive mutations affecting response to
      infection have accumulated in the more than 40 years that this B10.Q-H-2q MHC
      congenic strain has been separated from its B10-H-2b parental strain. During
      typical experiments with congenic strains, the phenotypes of these accumulated
      mutations will be falsely ascribed to the congenic gene(s). This problem likely
      affects any strains separated for appreciable time and while usually ignored, can
      be avoided with the use of F2 segregants.

PMID- 15245583
TI  - The uveo-meningeal syndromes.
AB  - BACKGROUND: The uveo-meningeal syndromes are a group of disorders that share
      involvement of the uvea, retina, and meninges. REVIEW SUMMARY: We review the
      clinical manifestations of uveitis and describe the infectious, inflammatory, and
      neoplastic conditions associated with the uveo-meningeal syndrome. CONCLUSIONS:
      Inflammatory or autoimmune diseases are probably the most common clinically
      recognized causes of true uveo-meningeal syndromes. These entities often cause
      inflammation of various tissues in the body, including ocular structures and the
      meninges (eg, Wegener granulomatosis, sarcoidosis, Behcet disease, Vogt-Koyanagi
      Harada syndrome, and acute posterior multifocal placoid pigment epitheliopathy).
      The association of an infectious uveitis with an acute or chronic
      meningoencephalitis is unusual but occasionally the eye examination may suggest
      an infectious etiology or even a specific organism responsible for a meningeal
      syndrome. One should consider the diagnosis of primary ocular-CNS lymphoma in
      patients 40 years of age or older with bilateral uveitis, especially with
      prominent vitritis, that fails to respond to treatment or who has associated
      neurologic findings. A paraneoplastic disorder has been described in patients who
      have combined optic neuritis and retinitis defined serologically by the presence
      of a paraneoplastic IgG autoantibody CRMP-5-IgG. These patients may have an
      inflammatory vitritis and may have signs of cerebrospinal fluid inflammation.

PMID- 15245585
TI  - How important is hyperglycemia during acute brain infarction?
AB  - BACKGROUND: Although well supported by animal studies, it remains unproven
      whether lowering hyperglycemia during acute cerebral infarction will improve
      outcomes. Further support for this therapeutic approach comes from clinical
      studies in acute myocardial infarction and in ventilated postsurgical patients,
      where lowering hyperglycemia improved outcomes. REVIEW SUMMARY: Animal studies
      support the hypothesis that hyperglycemia during acute brain ischemia augments
      the brain injury, but only in models with reperfusion. The available human
      studies to date are all observational and they usually find an association
      between hyperglycemia during acute cerebral infarction and worse outcome. Also,
      there is evidence that hyperglycemia during acute cerebral infarction is
      detrimental only with reperfusion. This association appears to be linear in the
      glucose ranges tested (normal to high). In addition, there is an association
      between admission hyperglycemia and hemorrhagic conversion of an acute cerebral
      infarct when thrombolytics are used. CONCLUSION: Sufficient evidence has
      accumulated to proceed to clinical efficacy trials to see if tight glycemic
      control compared with persistent hyperglycemia during acute cerebral infarction
      will improve outcomes. If such therapy proves beneficial, the increased cost,
      effort, and risk associated with tight glycemic control during acute cerebral
      infarction could be justified. Randomized clinical trials to test this hypothesis
      are currently in progress.

PMID- 15245586
TI  - Familial multiple sclerosis and other inherited disorders of the white matter.
AB  - BACKGROUND: An objective demonstration of lesions disseminated in time and space
      remains the core of the last revision of diagnostic criteria for multiple
      sclerosis (MS), but this update is now empowered by a weighted use of magnetic
      resonance imaging (MRI), which results in an earlier and more unambiguous
      diagnosis ("MS," "not MS," or "possible MS"). Nevertheless, the exclusion of
      other entities still remains an integral element of the diagnostic process.
      REVIEW SUMMARY: Exclusion of genetic disorders can be challenging in some cases
      with familial recurrence of MS, particularly when the transmission is mimicking a
      mendelian or a maternal pattern of inheritance. Vice versa, many forms of
      mendelian leukodystrophies and leukoencephalopathies present with juvenile or
      adult onset, progressive or relapsing-remitting courses, intrafamilial phenotypic
      heterogeneity and MRI signs of multifocal white matter (WM) pathology, features
      potentially leading to a temporary confusion with MS. With the recent
      availability of disease modifying medications in MS, the development of specific
      molecular therapies in inherited WM disorders, and the general recognition of the
      effectiveness of early treatments, the accuracy of initial diagnostic assessment
      has become critical. CONCLUSION: Considering the importance of disease specific
      treatments, here we review the major characteristics of familial MS and some of
      the inheritable diseases of the WM. Although no direct genetic link between MS
      and these WM abnormalities is known, molecular data from the field of rare
      genetic disorders may also provide some experimental paradigms to a further
      exploration of MS.

PMID- 15245587
TI  - The challenges of residents teaching neurology.
AB  - BACKGROUND: Teaching is integrated into the daily practice of residents, and it
      is a skill necessary for practice as well as academics. The settings in which
      teaching and learning take place are ubiquitous but include classrooms, small
      groups, bedside rounds, and grand rounds. Given the learning environment of
      residency, neurology residents should have working knowledge of basic principles
      of effective teaching to make learning successful. Teaching also reinforces
      knowledge, and residents will likely be better practitioners if some basic skills
      of teaching are practiced. REVIEW SUMMARY: Neurology teaching techniques for
      residents are rarely addressed in the medical literature. Although information
      regarding teaching principles in medicine exists, there is little information
      regarding how residents teach. We examine and review some of the more effective
      methods and appreciated qualities in teachers, with a particular emphasis for the
      neurology resident. We also review whom neurologists need to teach and the
      various settings in which teaching may take place. CONCLUSIONS: Neurology
      residents encounter a variety of audiences in a variety of settings that require
      diverse teaching skills to effectively convey information to other providers as
      well as patients. The majority of these skills should be learned in residency to
      establish a foundation for teaching, regardless of future practice settings.

PMID- 15245584
TI  - Parkinson disease: an update.
AB  - BACKGROUND: Over the past decade, the treatment of Parkinson disease (PD) has
      undergone tremendous changes. New drugs have been introduced to manage the
      cardinal motor symptoms of PD, and other agents have been borrowed to treat the
      nonmotor manifestations of the illness. For neurologists faced with the task of
      treating PD patients, the available array of medications may be confusing and
      intimidating. REVIEW SUMMARY: In this review, I summarize the newest approved
      medications for the treatment of PD, including the new dopamine agonists and
      catechol-O-methyl-transferase inhibitors. I also describe agents that are used to
      treat common problems in PD patients, including hallucinations, orthostasis,
      nausea, erectile dysfunction, depression, and memory loss. Guidelines for
      handling common scenarios in PD patients will be illustrated by 10 case
      histories. Finally, the most promising PD drugs that are currently in development
      will be reviewed. CONCLUSIONS: Neurologists have a vast armamentarium to treat
      both motor and nonmotor manifestations of PD. Understanding this array allows the
      astute clinician to improve the lives of their patients with PD.

PMID- 15245588
TI  - Interactions between Neisseria meningitidis and human cells that promote
      colonisation and disease.
AB  - Neisseria meningitidis is the leading cause of bacterial meningitis, a
      potentially fatal condition that particularly affects children. Multiple steps
      are involved during the pathogenesis of infection, including the colonisation of
      healthy individuals and invasion of the bacterium into the cerebrospinal fluid.
      The bacterium is capable of adhering to, and entering into, a range of human cell
      types, which facilitates its ability to cause disease. This article summarises
      the molecular basis of host-pathogen interactions at the cellular level during
      meningococcal carriage and disease.

PMID- 15245589
TI  - Heparanase as a molecular target of cancer chemotherapy.
AB  - Cancer cells require the ability to degrade the extracellular matrix (ECM) in
      order to turn into invasive and metastatic cancer cells. Many proteases and
      glycosidases are essential in the process of dissolving the components of the
      ECM. An endo-beta-D-glucuronidase, heparanase, is capable of specifically
      degrading one of the ECM components, heparan sulfate, and this activity is
      associated with the metastatic potential of tumor cells. Since heparanase mRNA is
      overexpressed in many human tumors (e.g., hepatomas, head and neck tumors, and
      esophageal carcinomas), the mechanisms regulating the activity of heparanase
      should be clarified; considering the possible role of heparanase in cancer, the
      development of heparanase inhibitors would appear to be advantageous. This review
      will focus on recent findings that have contributed to the characterization of
      heparanase and to the elucidation of the transcriptional regulation of heparanase
      mRNA expression, as well as the development of heparanase inhibitors.

PMID- 15245590
TI  - Comparative genomic hybridization (CGH)-arrays pave the way for identification of
      novel cancer-related genes.
AB  - Comparative genomic hybridization (CGH) has already made a significant impact on
      cancer cytogenetics. However, CGH to metaphase chromosomes can provide only
      limited resolution at the 5-10 Mb level. To circumvent this limitation, array
      based CGH has been devised. Since spotted DNAs in a CGH-array contain sequence
      information directly connected with the genome database, we can easily note
      particular biological aspects of genes that lie within regions involved in copy
      number aberrations. High-density, sub-megabase arrays can reveal nonrandom
      chromosome copy-number aberrations responsible for neoplastic transformation that
      have been masked under complex karyotypes in epithelial solid tumors. High
      density CGH-array therefore paves the way for identification of disease-related
      genetic aberrations that have not yet been detected by existing technologies, and
      array-based CGH technology should soon be practical for diagnosis of cancer or
      genetic diseases in the clinical setting.

PMID- 15245591
TI  - Prompt tumor formation and maintenance of constitutive NF-kappaB activity of
      multiple myeloma cells in NOD/SCID/gammacnull mice.
AB  - Clinically and biologically relevant animal models are indispensable to evaluate
      both the pathophysiology and strategies for diagnosis and treatment of multiple
      myeloma (MM). We examined the tumorigenicity of MM cell lines KMM-1 and U-266 in
      an in vivo cell proliferation model using NOD/SCID/gammacnull (NOG) mice. Two
      cell lines were inoculated either subcutaneously (s.c.) in the post-auricular
      region or intravenously (i.v.) in the tail of NOG mice. The KMM-1 cell line
      produced a progressively growing large tumor with infiltration of the cells
      expressing human lambda-chain in various organs of all NOG mice, while the U-266
      cell line failed to do so. Tumor cells grown in NOG mice maintained the original
      histomorphology, as well as expression patterns of tumor markers human lambda Ig
      light chain and VEGF. Tumor progression in mice also correlated with elevation of
      serum human soluble IL-6R and gp130. Tumor cells sustained a strong NF-kappaB
      activity in vivo and induced NF-kappaB components were indistinguishable from
      those in cells cultured in vitro. The rapid and efficient engraftment of the MM
      cell line in NOG mice suggests that this is a very useful animal model which
      could provide a novel system in which to clarify the mechanism of growth of
      cancer cells, as well as to develop new therapeutic regimens against MM.

PMID- 15245592
TI  - Frequent and preferential infection of Treponema denticola, Streptococcus mitis,
      and Streptococcus anginosus in esophageal cancers.
AB  - Multiple cancers frequently occur in the upper digestive tract. One possible
      explanation is that specific bacterial infection stimulates the normal epithelium
      to initiate inflammation and/or promotes carcinogenesis. This study was
      undertaken to determine which bacterial species is predominantly associated with
      esophageal cancer. We examined the bacterial diversity in this type of cancer and
      in the saliva from healthy people by using a culture-independent molecular
      method. Here we report the preferential and frequent infection of the oral
      periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus
      mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer
      from different regions of the world, and we also describe the induction of
      inflammatory cytokines by infection of S. anginosus and S. mitis. Our present
      data suggest that these three bacteria could have significant roles in the
      carcinogenic process of many cases of esophageal cancer by causing inflammation
      and by promoting the carcinogenic process, and that eradication of these three
      bacteria may decrease the risk of recurrence.

PMID- 15245593
TI  - Establishment of two cell lines from human gastric scirrhous carcinoma that
      possess the potential to metastasize spontaneously in nude mice.
AB  - Few experimental studies have been conducted to clarify the mechanism of
      development of metastasis in scirrhous carcinoma of the stomach. In the present
      study, we attempted to establish gastric carcinoma cell lines by incubation of
      cancer cells collected from the body fluids of patients with gastric cancer. At
      the same time, xenografting of these cells to nude mice was performed. It was
      found that, of the gastric carcinoma cell lines thus established, two cell lines,
      designated as HSC-44PE and HSC-58, formed s.c. tumors with a high infiltrative
      potential (often invading the lymphatics around the cancer tissue) when
      implanted. Metastasis to the lymph nodes and lungs was observed in 20-40% of all
      the animals, indicating that the two cell lines are also capable of metastasizing
      spontaneously. Through repeated selection, i.e., repeated cycles of removal,
      culture, and implantation of the HSC cancer cells from metastatic lesions, we
      obtained 5 subclones of HSC-44PE and HSC-58 (designated as m2509, m2615, m2792,
      m2917, and m2691), which, when implanted orthotopically, exhibited the following
      characteristics as compared to the parent cells: (1) a higher percentage take
      (survival), similar frequency of metastasis, shorter time to metastasis (less
      than 100 days), and consistent metastasizing potential; (2) a relatively high
      frequency of metastasis to lymph nodes, including distant metastasis to axillary
      lymph nodes; (3) the potential to cause occasional bloody ascites; (4) enhanced
      expression of dysadherin, CD44, and other molecules. This is the first report of
      cultured scirrhous gastric carcinoma cells showing the potential for spontaneous
      metastasis.

PMID- 15245594
TI  - Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma.
AB  - The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry
      in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30
      (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10
      (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No
      correlations between WT1 expression and clinicopathological parameters such as
      age, sex, T or N stage, tumor location, and tumor differentiation were observed.
      Treatment with WT1 antisense oligomers significantly inhibited the growth of five
      human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6,
      expressing the WT1 gene. These results indicate an important role of the WT1 gene
      in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and
      provide a rationale for new treatment strategies to treat pancreatic ductal
      adenocarcinoma by targeting the WT1 gene and its product.

PMID- 15245595
TI  - Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer.
AB  - It has recently been reported that CDH13 expression is silenced by aberrant
      methylation of the promoter region in several cancers. We examined the
      methylation status of the CDH13 gene in pancreatic cancer using methylation
      specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6
      pancreatic cancer cell lines examined. To confirm the status of the CDH13 gene in
      relation to the methylation pattern, we next examined CDH13 expression in these
      cell lines using reverse transcription (RT)-PCR. As expected, no CDH13 expression
      was detected in any of the 6 pancreatic cancer cell lines. Moreover, 5-aza-2'
      deoxycytidine (5-aza-dC) treatment of CDH13-methylated cell lines led to
      restoration of CDH13 expression. Among primary pancreatic cancers, 19 of 33 (58%)
      cases exhibited CDH13 methylation, while no cases exhibited it in corresponding
      normal pancreatic tissues. CDH13 methylation was detected even in relatively
      early pancreatic cancers, such as stage II cancers and cancers less than 2 cm in
      diameter. Our results suggest that the aberrant methylation of CDH13 occurs
      frequently in pancreatic cancer, even at a relatively early stage.

PMID- 15245596
TI  - Hepatitis C virus infection as a likely etiology of intrahepatic
      cholangiocarcinoma.
AB  - Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk
      factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have
      tested this hypothesis. We investigated ICC risk factors, with special reference
      to HCV infection. We conducted a hospital-based case-control study including 50
      ICC patients and 205 other surgical patients without primary liver cancer. HCV
      seropositivity was detected in 36% of ICC patients and 3% of controls. By
      univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies
      with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History
      of blood transfusion or diabetes mellitus, elevated serum total bilirubin,
      elevated aspartate aminotransferase and alanine aminotransferase, decreased serum
      albumin and decreased platelet count were identified as other possible ICC risk
      factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95%
      CI, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin,
      and decreased platelet count were found to be independent risk factors for ICC
      development. As liver status worsened, the adjusted OR for ICC tended to
      increase. HCV infection is a likely etiology of ICC in Japan.

PMID- 15245597
TI  - HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is
      diminished by green tea drinking.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with
      adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating
      lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1
      provirus load in the circulation may prevent these intractable diseases. Our
      previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea
      polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T
      cells. The present study aimed to investigate the in vivo effect of green tea
      polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1
      carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus
      DNA with or without administration of capsulated green tea extract powder. Thirty
      seven subjects were followed up for 5 months by measuring HTLV-1 provirus load
      after daily intake of 9 capsules of green tea extract powder per day (equivalent
      to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake
      of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed
      a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1
      carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood
      lymphocytes). Daily intake of the capsulated green tea for 5 months significantly
      diminished the HTLV-1 provirus load as compared with the controls (P = 0.031).
      These results suggest that green tea drinking suppresses proliferation of HTLV-1
      infected lymphocytes in vivo.

PMID- 15245598
TI  - A prospective study of reproductive and menstrual factors and colon cancer risk
      in Japanese women: findings from the JACC study.
AB  - The effects of reproductive factors on the etiology of colon cancer in Asian
      populations remain unexplored. So we examined 38,420 Japanese women aged 40-79
      years who responded to a questionnaire on reproductive and other lifestyle
      factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation
      of Cancer Risk. During an average 7.6 years of follow-up, we documented 207
      incident colon cancers. Multivariate analysis indicated that colon cancer risk
      was likely to be lower among parous women than among nulliparous. Women who had
      two abortions or more had a 72% higher risk of developing colon cancer [relative
      risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared
      with women who never had an abortion. The RR of colon cancer among postmenopausal
      women significantly decreased with increasing age at menarche (trend P = 0.01).
      No apparent association between colon cancer and gravida, age at first birth, age
      at menopause, or duration of menstruation was seen. These prospective data
      support the hypothesis that female reproductive events modify colon cancer risk,
      and suggest that reproductive factors, particularly age at menarche and having an
      abortion, may be of importance in the etiology of colon cancer among Japanese
      women.

PMID- 15245599
TI  - Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly
      developed monoclonal antibody GAH, in colorectal cancer xenografts.
AB  - MCC-465 is an immunoliposome-encapsulated doxorubicin. The liposome is tagged
      with polyethylene glycol and the F(ab')2 of a monoclonal antibody named GAH, a
      human antibody obtained by the hybridoma technique. The epitope recognized by GAH
      is not well characterized, but human gastric, colorectal, and mammary cancer
      cells were GAH-positive, while the normal counterparts were GAH-negative.
      Pegylated liposome doxorubicin (PLD) and MCC-465 did not show significant
      antitumor activity against GAH-negative Caco-2 xenografts. On the other hand, MCC
      465 exhibited significantly superior antitumor effects against GAH-positive WiDr
      Tc and SW837 xenografts, compared with PLD. Immunohistochemistry with GAH
      revealed that 94% (100 of 106) of surgical specimens of colorectal cancer were
      GAH-positive. These results warrant a phase I clinical trial of MCC-465 for
      patients with metastatic colorectal cancer.

PMID- 15245600
TI  - Direct inhibition of EGF receptor activation in vascular endothelial cells by
      gefitinib ('Iressa', ZD1839).
AB  - The development of gefitinib ('Iressa', ZD1839) by targeting the EGFR tyrosine
      kinase is a recent therapeutic highlight. We have reported that gefitinib is
      antiangiogenic in vitro, as well as in vivo. In this study, we asked if the anti
      angiogenic action of gefitinib is due to a direct effect on activation of
      vascular endothelial cells by EGF. EGF, as well as VEGF, caused pronounced
      angiogenesis in an avascular area of the mouse cornea, and i.p. administration of
      gefitinib almost completely blocked the response to EGF, but not to VEGF.
      Immunohistochemical analysis demonstrated phosphorylation of EGFR by EGF in the
      neovasculature, and gefitinib markedly reduced this effect. Gefitinib also
      inhibited downstream activation of ERK 1/2 via EGFR in cultured microvascular
      endothelial (HMVE) cells. These findings suggest that the anti-angiogenic effect
      of gefitinib in the vascular endothelial cells of neo-vasculature is partly
      attributable to direct inhibition of EGFR activation, and that endothelial cells
      in malignant tumors play a critical role in the cancer therapeutic efficacy of
      gefitinib.

PMID- 15245601
TI  - 8th annual International Congress on Hematological Malignancies, March 2004,
      Whistler, British Columbia, Canada.

PMID- 15245604
TI  - Molecular diagnosis and outcome prediction in diffuse large B-cell lymphoma and
      other subtypes of lymphoma.
AB  - Lymphoid malignancies are grouped and characterized by their morphology,
      immunophenotype, and genetic aberrations to help establish a diagnosis. Use of
      microarray technology enables the simultaneous determination of expression levels
      for thousands of genes, providing an additional powerful tool for improving
      disease classification. In this review, recent studies of diffuse large B-cell
      lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, mantle cell lymphoma
      (MCL), and follicular lymphoma are highlighted, and the impact of gene expression
      profiling on the molecular diagnosis of these diseases is discussed. Based on
      microarray-generated gene expression profiles, outcome predictors were
      constructed for DLBCL and MCL. Specific expression patterns of a limited number
      of genes at the time of diagnosis were linked to overall survival in DLBCL and
      MCL. Such predictors of prognosis may eventually lead to risk-adjusted treatment
      of lymphomas. Specific therapeutic targets may also emerge with increased insight
      into the molecular features of the different lymphomas, thus illustrating the
      usefulness of gene expression profiling not only to improve diagnosis and
      classification but also to generate prognostic indicators and targets for
      therapy.

PMID- 15245605
TI  - Paraneoplastic manifestations of lymphoma.
AB  - Paraneoplastic syndromes are manifestations of malignancies that have produced
      effects that are distant from the primary tumor or metastases. Paraneoplastic
      syndromes are not caused by local effects of compression or infiltration into
      tissues, but are generally due to ectopic hormone production, autoimmune
      phenomena, or overproduction of cytokines. Paraneoplasia may be the presenting
      symptom of underlying malignancy and can affect almost any organ system, such as
      the neurologic syndromes associated with small-cell lung cancer or hypercalcemia
      associated with squamous cell carcinomas. Lymphoproliferative disorders are also
      associated with many paraneoplastic disorders; however, to date, most published
      information has been in the form of case reports and series of small numbers of
      patients. In this review, the most common paraneoplastic syndromes associated
      with non-Hodgkin's lymphoma and Hodgkin's disease will be discussed.

PMID- 15245606
TI  - Treatment of non-Hodgkin's lymphomas in elderly patients.
AB  - The roles of evolving treatment strategies for non-Hodgkin's lymphomas (NHL) in
      elderly patients are still not well defined and their effects on the overall
      epidemiology of the disease are still not clear. Three questions arise when
      discussing the management of NHL in elderly patients. First, should older
      patients be treated with the same regimens usually administered to younger
      patients? Second, are health outcomes of elderly patients similar to those
      usually observed in young patients, particularly response rate and overall
      survival? Third, which strategies should be adopted to improve overall health
      outcomes? Periodic review of the literature and updated data on the management of
      NHL in elderly patients may provide an answer to all these queries. In essence,
      older patients must be treated with the same intensive approaches that are
      usually reserved for younger patients. The results reported in randomized
      controlled clinical trials are consistent with the capability of older patients
      to exhibit overall response rate, event-free survival, and overall survival
      similar to those observed in their younger counterparts. Combining chemotherapy
      and monoclonal antibodies seems to be the main optional strategy for better
      outcomes in elderly patients. In contrast, knowledge concerning the management of
      indolent lymphomas in elderly patients is still lacking, and available clinical
      data are limited in this setting, especially in patients with poor prognostic
      factors who may need an immediate therapeutic intervention.

PMID- 15245607
TI  - Pilot study of fixed-infusion rate gemcitabine with Cisplatin and dexamethasone
      in patients with relapsed or refractory lymphoma.
AB  - Management of patients with multiple-relapsed lymphoma meets with little success.
      The optimal use of available drugs in this situation is often unknown.
      Gemcitabine has documented efficacy in this setting. Pharmacodynamic data suggest
      that the optimal use may involve a fixed-rate infusion and coadministration with
      platinum compounds. In this study we explored the use of gemcitabine starting at
      a dose of 800 mg/m(2) administered at a fixed infusion rate of 10 mg/m(2) per
      minute with cisplatin 35 mg/m(2) intravenously, both given on day 1, and
      dexamethasone 20 mg daily for 4 days; the treatment was given every 2 weeks (days
      1 and 15 of a 28-day cycle) for the treatment of relapsed Hodgkin's and non
      Hodgkin's lymphoma. Dose escalation of gemcitabine was allowed according to phase
      I criteria. Twenty-two patients with a median of 4 prior treatments were enrolled
      (Hodgkin's lymphoma, n = 7; B-cell non-Hodgkin's lymphoma, n = 9; T-cell non
      Hodgkin's lymphoma, n = 6). Ten patients had relapsed after prior autologous
      transplantation. Grade 4 thrombocytopenia and neutropenia were the dose-limiting
      toxicities and occurred in 9 patients (41%) and 4 patients (18%), respectively.
      Initial dose escalation of gemcitabine was not possible. Responses were observed
      in 45% of the patients: 2 of 5 with T-cell non-Hodgkin's lymphoma (1 patient
      withdrew after first treatment and was evaluable only for toxicity), 4 of 7 with
      Hodgkin's lymphoma, and 4 of 9 with B-cell non-Hodgkin's lymphoma. The
      coadministration of gemcitabine 800 mg over 80 minutes with low-dose cisplatin
      and dexamethasone is feasible and sufficiently active in a heavily pretreated
      patient population with lymphoma.

PMID- 15245608
TI  - A large-scale study of bone marrow involvement in patients with Hodgkin's
      lymphoma.
AB  - This study was designed to identify variables that can predict bone marrow
      involvement (BMI) in Hodgkin's lymphoma (HL), and to analyze the benefit of
      bilateral over unilateral bone marrow trephine biopsy (BMB). From 1982 to 2000,
      BMB had been performed at diagnosis in 1161 patients with HL who had been
      followed from the institutions participating in the Piemonte Hodgkin's Disease
      Registry. Six hundred and sixteen patients (53%) had received bilateral BMB, and
      the remaining 545 patients (47%) received unilateral BMB. The relationships
      between BMB results and other clinical features were retrospectively studied with
      both univariate and multivariate analyses. Ninety-two patients (8%) showed BMI:
      51 of them were staged with bilateral and 41 with unilateral BMB. Among the 92
      patients with BMI, a second extranodal involvement was present in only 25
      patients (27%). In multivariate analysis, the 5 independent factors that
      predicted for BMI were B symptoms, infradiaphragmatic involvement, mixed
      cellularity (MC) and lymphocyte depleted (LD) histology, involvement of > or = 4
      lymphatic areas, and liver involvement. The probability of BMI according to the
      presence of these variables was distributed as follows: 0.3%, 2.5%, 7.6%, and 27%
      in patients positive for 0, 1, 2, and > or = 3 factors, respectively. Among 51
      patients staged with bilateral BMB, BMI was shown in both specimens in 33 cases
      (65%), whereas the positivity was limited to only 1 of the 2 specimens in the
      remaining 18 cases (35%). A score based on 5 variables can predict the
      probability of BMI, and BMB could be avoided in patients with a score of 0 and a
      probability of BMI of < 0.5%. When BMB is needed, the superiority of bilateral
      over unilateral biopsy is suggested.

PMID- 15245609
TI  - The use of gallium-67 scintigraphy to monitor tumor response rates and predict
      long-term clinical outcome in patients with lymphoma.
AB  - The aim of this study was to determine whether gallium (Ga)-67 scintigraphy can
      monitor the treatment response rates and predict the long-term clinical outcome
      in patients with lymphoma. Gallium-67 scintigraphy was performed upon admission
      (baseline Ga) in 33 consecutive, newly diagnosed patients. Twenty-eight patients
      (Hodgkin's disease, n = 18; non-Hodgkin's lymphoma, n = 13) with Ga avid tumors
      were included in the study. All the patients were treated with induction
      chemotherapy. Gallium-67 scintigraphy was performed in all patients after the
      first cycle of chemotherapy (post-cycle 1 Ga) and repeated after the fourth cycle
      (post-cycle 4 Ga) or after completion of treatment (end-of-chemotherapy Ga).
      Nineteen patients had a fast response (68%, negative in post-cycle 1 and end-of
      chemotherapy Ga), 4 intermediate response (14%, partial positive post-cycle 1 Ga
      that progressed to negative post-cycle 4 Ga), 3 slow response (11%, partial
      positive in both post-cycle 1 and post-cycle 4 Ga) and 2 no response (7%,
      positive in both post-cycle 1 and end-of-chemotherapy Ga). In patients who had
      either fast or intermediate response, 22 (96%) were free of disease at a median
      follow-up period of 30 months (range, 11-45 months). All 5 patients (100%) who
      had slow or no response had progressive disease or residual disease. In
      conclusion, the findings indicate that Ga could effectively be used to monitor
      the treatment response rates and predict the long-term clinical outcome in
      patients with lymphoma and should be used in treatment modifications aimed at
      reducing toxicity of effective therapy in patients with fast response and
      replacing treatments early in patients with slow or no response.

PMID- 15245610
TI  - Enhanced marrow [18F]fluorodeoxyglucose uptake related to myeloid hyperplasia in
      Hodgkin's lymphoma can simulate lymphoma involvement in marrow.
AB  - [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly
      used for the clinical staging of lymphomas and for assessment of response to
      therapy. We report the case of a woman with classic Hodgkin's lymphoma who had
      marked FDG uptake by tumor and bone marrow suggestive of diffuse marrow
      involvement by lymphoma. However, iliac crest bone marrow examination showed
      marked myeloid hyperplasia without evidence of lymphoma involvement. We discuss
      the implications for interpretation of FDG-PET imaging of bone marrow in
      lymphomas.

PMID- 15245612
TI  - The prevention of adjuvant hormonal therapy-induced bone loss in women with
      breast cancer.

PMID- 15245613
TI  - Monitoring the circulating levels of the HER2/neu oncoprotein in breast cancer.
AB  - The HER2/neu oncoprotein is a major target for the development of new cancer
      therapies and is similar to the estrogen receptor, which guides hormone therapy.
      The HER2/neu status is used to guide therapy decisions in patients with HER2/neu
      overexpressing breast cancer tumors. The HER2/neu oncogene, or c-erbB-2, encodes
      a transmembrane receptor protein that is expressed on normal epithelial cells and
      can be overexpressed in breast cancer cells. Studies have shown that the
      extracellular domain (ECD) of the HER2/neu oncoprotein is released from the cell
      and can be measured in the circulation of women with breast cancer. Enzyme-linked
      immunosorbent assay methods used to measure the circulating HER2/neu ECD have
      shown that the prevalence of elevated ECD levels is approximately 18.1% in women
      with primary breast cancer and approximately 45.6% in women with metastatic
      breast cancer (MBC). Many studies have monitored the circulating ECD levels after
      surgery and indicate that increasing ECD levels can indicate recurrence of breast
      cancer earlier than clinical diagnosis. Studies in women with MBC showed that
      serial changes in circulating HER2/neu ECD levels paralleled the clinical course
      of disease, regardless of the treatment regimen. Several studies identified a
      subgroup of patients with MBC who had HER2/neu-negative disease by tissue testing
      but developed elevated ECD levels with MBC. In contrast to tissue testing, which
      is a one-time event, monitoring the circulating levels of the HER2/neu ECD in
      patients with breast cancer provides a real-time assessment of the HER2/neu
      status and provides important information for managing the therapy of patients
      with MBC.

PMID- 15245614
TI  - Gemcitabine plus carboplatin combination therapy as second-line treatment in
      patients with relapsed breast cancer.
AB  - This study was designed to determine the safety and efficacy of the combination
      therapy of gemcitabine plus carboplatin when used as a second-line treatment in
      patients with metastatic breast cancer (MBC). From February 2002 to May 2003, 30
      previously treated patients with adenocarcinoma of the breast received
      gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the
      curve (AUC) of 5 on day 1. The carboplatin dose was changed to an AUC of 4.5
      because of toxicity, with cycles repeated every 3 weeks. Among 30 patients
      enrolled, 25 were assessable for response rate (RR). There was no complete
      response; 9 patients (30%) had partial response, for an overall RR of 30%. The
      median time to progression for the study group was 20.47 weeks (range, 8-46
      weeks). Treatment-related toxicities included grade 3/4 neutropenia in 50% of
      patients (20% of whom had febrile neutropenia), grade 3/4 anemia in 26.6% of
      patients, and grade 3/4 thrombocytopenia in 30%. Eleven patients (36.67%) had
      grade 1 alopecia, and 1 patient (3.33%) had grade 2 alopecia. Moderate nausea was
      observed in 8 patients (26.67%), and vomiting occurred in 7 patients. Four
      patients had asthenia and 3 (10%) experienced stomatitis. Three patients
      discontinued treatment because of hematologic toxicity (thrombocytopenia) and 2
      patients are still receiving treatment. Carboplatin plus gemcitabine is an active
      combination for patients with MBC despite significant but manageable hematologic
      toxicity.

PMID- 15245616
TI  - Adjuvant therapy for very young women with breast cancer: response according to
      biologic and endocrine features.
AB  - Incidence of breast cancer in patients aged < 20 years has been estimated to be
      0.1 per 100,000 women. Reported incidences are 1.4 for women aged 20-24 years,
      8.1 for women aged 25-29 years, and 24.8 for women aged 30-34 years. Younger
      patients have been found to have a more aggressive presentation of disease at
      diagnosis, which is associated with dire prognoses compared with those in
      premenopausal older patients. Several biologic features might explain the more
      aggressive behavior of breast cancer in younger patients: higher grade and higher
      expression of Ki67, higher occurrence of vessel invasion, and less expression of
      estrogen and progesterone receptors. Choice of adjuvant therapies for women aged
      <35 years with breast cancer is based on data derived from trials on cohorts of
      older patients. On average, the effect of chemotherapy for premenopausal patients
      is substantial: recent evidence suggested that very young women with endocrine
      responsive tumors had a higher risk of relapse than older premenopausal patients
      with similar tumors. This was not the case for patients with endocrine
      nonresponsive tumors, for which effects of chemotherapy were similar across ages.
      Very young women with this disease are faced with personal, family, professional,
      and quality-of-life issues that further complicate the phase of treatment
      decision-making. The development of more effective therapies for very young women
      with breast cancer requires tailored treatment investigations and research
      focused on issues specific to these patients.

PMID- 15245617
TI  - Biweekly docetaxel and vinorelbine as first-line chemotherapy in metastatic
      breast cancer.
AB  - This study was designed to evaluate the antitumor activity and tolerance of
      biweekly docetaxel plus vinorelbine as first-line chemotherapy in patients with
      metastatic breast cancer (MBC). Forty-one patients with measurable disease and no
      prior chemotherapy for MBC were treated with docetaxel 60 mg/m(2) plus
      vinorelbine 30 mg/m(2) on day 1, every 2 weeks for a maximum of 12 courses.
      Median age was 58 years (range, 23-75). Fourteen patients (34.1%) were
      premenopausal and 27 (65.9%) were postmenopausal. Most patients had received
      prior neoadjuvant/adjuvant chemotherapy (n = 27, 65.9%), radiation therapy (n =
      22, 53.6%), and hormone therapy (n = 21, 51.2%). The most frequent sites of
      metastasis were bone (n = 18, 43.9%), pleuropulmonary (n = 16, 39%), and liver (n
      = 14, 34.1%). Twenty-seven patients (65.9%) had more than one site of metastasis.
      Three hundred and thirty-nine courses were given (median, 8 courses per patient;
      range, 1-12). Median relative dose intensity was 85% for both docetaxel and
      vinorelbine. Grade 3/4 toxicities included neutropenia (14 patients, 34.1%),
      febrile neutropenia (n = 14, 34.1%), and stomatitis (n = 4, 9.8%). No treatment
      related deaths were reported. All patients were assessed for response in an
      intent-to-treat analysis. Four patients (9.8%) had a complete response and 19
      (46.3%) had a partial response (overall response rate, 56.1%; 95% CI, 42%-70%).
      Six patients (14.6%) had stable disease and 12 patients (29.3%) had progressive
      disease. With a median follow-up of 15.1 months or until death, median duration
      of response is 12.6 months. Median time to progression is 12.4 months. Median
      survival time is 19.6 months. This biweekly combination of docetaxel plus
      vinorelbine is feasible and active as first-line chemotherapy in patients with
      MBC. This regimen is safe and well tolerated.

PMID- 15245618
TI  - High-dose oral medroxyprogesterone acetate or tamoxifen as adjuvant hormone
      therapy for node-negative early-stage breast cancer: randomized trial with 7-year
      update.
AB  - A randomized adjuvant trial compared tamoxifen 20 mg daily for 5 years with high
      dose oral medroxyprogesterone acetate (MPA) 1 g orally for 9 months. One hundred
      ninety-four patients with histologically proven primary node-negative breast
      carcinoma were enrolled between December 1990 and October 1996, with 98 patients
      randomized into the tamoxifen arm and 96 into the MPA arm. At a median follow-up
      of 86 months, 25 relapses and 13 deaths were recorded. The relapse-free survival
      rate at 7 years in the tamoxifen arm was 93%, versus 81% in the MPA arm (P =
      0.02). The difference was observed in patients with stage T2 disease (100% in the
      tamoxifen group vs. 64% in the MPA group; P = 0.01), in younger and/or
      premenopausal patients (in patients < 50 years of age, 100% in the tamoxifen arm
      vs. 81% in the MPA arm [P = 0.02], and in patients > or = 50 years of age, 90% in
      the tamoxifen arm vs. 82% in the MPA arm [P = 0.16]). Also, the overall survival
      rate at 7 years was lower in women < 50 years of age (P = 0.04).

PMID- 15245619
TI  - Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated
      patients with metastatic breast cancer.
AB  - We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in
      patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients
      were enrolled, the majority of whom (95%) had been treated with an anthracycline
      and a taxane before study enrollment. Eligible women were treated with
      gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day
      cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg
      thereafter) until disease progression. The median patient age was 55 years, and
      the median number of previously administered (including adjuvant) chemotherapy
      regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by
      immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2
      negative on central pathology review and were ineligible for evaluation. Fifty
      nine of the 61 patients remained evaluable for response. The objective response
      rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39
      patients with HER2 3+ expression. The median response duration was 5.8 months,
      median overall survival was 14.7 months, and median time to disease progression
      was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of
      clinical congestive heart failure occurred. Grade 3/4 toxicities included
      asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or
      back pain in 3, and edema and nausea in 1 patient each. The combination of
      trastuzumab plus gemcitabine appears to be well tolerated and effective for
      patients with HER2-positive MBC previously treated with chemotherapy.

PMID- 15245620
TI  - Targeting the ubiquitin-proteasome pathway in breast cancer.
AB  - The 26S proteasome is an adenosine triphosphate-dependent multicatalytic protease
      that is responsible for most nonlysosomal intracellular protein degradation. To
      be selected for proteasomal degradation, proteins must be previously tagged with
      a polyubiquitin chain, which is then recognized by the proteasome; the ubiquitin
      chain is removed by isopeptidases and the protein is hydrolysed to small
      polypeptides. In addition to removing damaged/unnecessary proteins, the
      proteasome is also an important mechanism of regulation of some key regulatory
      proteins and their inhibitors. This regulation is crucial for the control of many
      cellular processes, including activation of transcription factors, cell cycle
      progression, and apoptosis. The critical role of the ubiquitin-proteasome pathway
      in tumor cells has led to the investigation of proteasome inhibition as a
      potential anticancer therapy. The dipeptide boronic acid analogue bortezomib,
      formerly known as PS-341, is a potent, highly selective, and reversible
      proteasome inhibitor. The first drug of this class to be used in the clinical
      setting, it has recently been approved by the US Food and Drug Administration for
      the treatment of relapsed and refractory multiple myeloma and is currently being
      tested in clinical trials for the treatment of a wide variety of malignancies.
      This article provides a summary of the biology of the ubiquitin-proteasome
      pathway, reviews the available preclinical and clinical data of proteasome
      inhibition as a therapeutic strategy in breast cancer, and discusses future
      combination regimens involving bortezomib.

PMID- 15245621
TI  - Graphical models for causation, and the identification problem.
AB  - This article (which is mainly expository) sets up graphical models for causation,
      having a bit less than the usual complement of hypothetical counterfactuals.
      Assuming the invariance of error distributions may be essential for causal
      inference, but the errors themselves need not be invariant. Graphs can be
      interpreted using conditional distributions, so that we can better address
      connections between the mathematical framework and causality in the world. The
      identification problem is posed in terms of conditionals. As will be seen, causal
      relationships cannot be inferred from a data set by running regressions unless
      there is substantial prior knowledge about the mechanisms that generated the
      data. There are few successful applications of graphical models, mainly because
      few causal pathways can be excluded on a priori grounds. The invariance
      conditions themselves remain to be assessed.

PMID- 15245622
TI  - Evaluation of treatment programs for persons with severe mental illness:
      moderator and mediator effects.
AB  - This study evaluated several statistical models for estimating treatment effects
      in a randomized, longitudinal experiment comparing assertive community treatment
      (ACT) versus brokered case management (BCM). In addition, mediator and moderator
      analyses were conducted. The ACT clients had improved outcomes in terms of
      housing and psychiatric symptoms than BCM clients. Case management housing
      assistance and financial assistance partially mediated housing outcomes. No
      reliable mediators were found for psychiatric symptoms, and no reliable
      moderators were found for either housing or psychiatric symptoms. The study also
      made several important methodological advances in the analysis of longitudinal
      data in randomized experiments.

PMID- 15245623
TI  - Evaluating child and youth homelessness.
AB  - Following a review of approaches taken to generate accurate estimates of the
      scale of child and youth homelessness in America, this article documents the
      methods and results of a multipronged count of homeless children and youth in New
      Haven, Connecticut. The survey used in this count accessed demographics and
      service needs, and was administered on the streets and in a wide range of service
      provision settings. A total of 170 homeless families were located, comprised
      primarily of young, single, African American women and their children. These
      families included 323 children, suggesting an annual prevalence of 1,688 in this
      community. This work addresses the paucity of information on homeless children
      and youth located in small to midsized cities

PMID- 15245624
TI  - Evaluating from the outside: conducting cross-cultural evaluation research on an
      American Indian reservation.
AB  - There is limited guidance for conducting competent and responsive cross-cultural
      evaluation research with American Indian communities. The authors draw on Fisher
      and Ball's Tribal Participatory Research Model to highlight ways in which this
      project is attempting to be culturally appropriate and sensitive as they partner
      with an American Indian community to implement and evaluate a youth-based
      initiative. Challenges encountered during the evaluation are shared, as well as
      the authors' collective responses to such challenges. Implications for future
      cross-cultural evaluation researchers are also discussed in light of these
      experiences.

PMID- 15245625
TI  - Unbinding biological autonomy: Francisco Varela's contributions to artificial
      life.

PMID- 15245626
TI  - Basic autonomy as a fundamental step in the synthesis of life.
AB  - In the search for the primary roots of autonomy (a pivotal concept in Varela's
      comprehensive understanding of living beings), the theory of autopoiesis provided
      an explicit criterion to define minimal life in universal terms, and was taken as
      a guideline in the research program for the artificial synthesis of biological
      systems. Acknowledging the invaluable contribution of the autopoietic school to
      present biological thinking, we offer an alternative way of conceiving the most
      basic forms of autonomy. We give a bottom-up account of the origins of "self
      production" (or self-construction, as we propose to call it), pointing out which
      are the minimal material and energetic requirements for the constitution of basic
      autonomous systems. This account is, indeed, committed to the project of
      developing a general theory of biology, but well grounded in the universal laws
      of physics and chemistry. We consider that the autopoietic theory was formulated
      in highly abstract terms and, in order to advance in the implementation of
      minimal autonomous systems (and, at the same time, make major progress in
      exploring the origins of life), a more specific characterization of minimal
      autonomous systems is required. Such a characterization will not be drawn from a
      review of the autopoietic criteria and terminology (a la Fleischaker) but demands
      a whole reformulation of the question: a proper naturalization of the concept of
      autonomy. Finally, we also discuss why basic autonomy, according to our account,
      is necessary but not sufficient for life, in contrast with Varela's idea that
      autopoiesis was a necessary and sufficient condition for it.

PMID- 15245627
TI  - The affirmation of self: a new perspective on the immune system.
AB  - The fundamental concepts of autopoiesis, which emphasize the circular
      organization underlying both living organisms and cognition, have been criticized
      on the grounds that since they are conceived as a tight logical chain of
      definitions and implications, it is often not clear whether they are indeed a
      scientific theory or rather just a potential scientific vocabulary of doubtful
      utility to working scientists. This article presents the deployment of the
      concepts of autopoiesis in the field of immunology, a discipline where working
      biologists themselves spontaneously have long had recourse to "cognitive"
      metaphors: "recognition"; a "repertoire" of recognized molecular shapes;
      "learning" and "memory"; and, most striking of all, a "self versus non-self"
      distinction. It is shown that in immunology, the concepts of autopoiesis can be
      employed to generate clear novel hypotheses, models demonstrating these ideas,
      testable predictions, and novel therapeutic procedures. Epistemologically, it is
      shown that the self-non-self distinction, while quite real, is misleadingly
      named. When a real mechanism for generating this distinction is identified, it
      appears that the actual operational distinction is between (a) a sufficiently
      numerous set of initial antigens, present from the start of ontogeny, in
      conditions that allow for their participation in the construction of the system's
      organization and operation, and (b) single antigens that are first presented to
      the system after two successive phases of maturation. To call this a self-non
      self distinction obscures the issue by presupposing what it ought to be the job
      of scientific investigation to explain.

PMID- 15245628
TI  - Thirty years of computational autopoiesis: a review.
AB  - Computational autopoiesis--the realization of autopoietic entities in
      computational media--holds an important and distinctive role within the field of
      artificial life. Its earliest formulation by Francisco Varela, Humberto Maturana,
      and Ricardo Uribe was seminal in demonstrating the use of an artificial,
      computational medium to explore the most basic question of the abstract nature of
      living systems--over a decade in advance of the first Santa Fe Workshop on
      Artificial Life. The research program it originated has generated substantive
      demonstrations of progressively richer, lifelike phenomena. It has also sharply
      illuminated both conceptual and methodological problems in the field. This
      article provides an integrative overview of the sometimes disparate work in this
      area, and argues that computational autopoiesis continues to provide an effective
      framework for addressing key open problems in artificial life.

PMID- 15245629
TI  - A possible route to prebiotic vesicle reproduction.
AB  - Spherical bounded structures such as those formed by surfactant aggregates
      (mostly micelles and vesicles), with an inside that is chemically and physically
      different from the outside medium, can be seen as primitive cell models. As such,
      they are fundamental structures for the theory of autopoiesis as originally
      formulated by Varela and Maturana. In particular, since self-reproduction is a
      very important feature of minimal cellular life, the study of self-reproduction
      of micelles and vesicles represents a quite challenging bio-mimetic approach. Our
      laboratory has put much effort in recent years into implementing self
      reproduction of vesicles as models for self-reproduction of cellular bounded
      structures, and this article is a further contribution in this direction. In
      particular, we deal with the so-called matrix effect of vesicles, related to the
      fact that when fresh surfactant is added to an aqueous solution containing
      preformed vesicles of a very narrow size distribution, the newly formed vesicles
      (instead of being polydisperse, as is usually the case) have dimensions very
      close to those of the preformed ones. In practice, this corresponds to a
      mechanism of reproduction of vesicles of the same size. In this article, the
      matrix effect is re-elaborated in the perspective of the origin of life, and in
      particular in terms of the prebiotic mechanisms that might permit the growth and
      reproduction of vesicles. The data are analyzed by dynamic light scattering with
      a new program that permits the calculation of the number-weighted size
      distribution. It is shown that, on adding a stoichiometric amount of oleate
      micelles to preformed oleate vesicles extruded at 50 and 100 nm, the final
      distribution contains about twice the initial number of particles, centered
      around 50 and 100 nm. The same holds when oleate is added to preformed
      phospholipid liposomes. By contrast, when the same amount of oleate is added to
      an aqueous solution (as a control experiment), a very broad distribution ranging
      between 20 and 1000 nm is obtained. The data can then be seen as a kind of
      reproduction of the same size vesicles, and the argument is advanced that this
      may correspond to a simple prebiotic mechanism of vesicle multiplication in
      prebiotic times, when only physical forces might be responsible for the basic
      mechanisms of early protocell growth and division. Preliminary data also show
      that repeated addition of oleate maintains the same basic initial features, and
      that surfactants other than oleate also respect the reproductive mode of the
      matrix effect.

PMID- 15245630
TI  - Autopoiesis and cognition in the game of life.
AB  - Maturana and Varela's notion of autopoiesis has the potential to transform the
      conceptual foundation of biology as well as the cognitive, behavioral, and brain
      sciences. In order to fully realize this potential, however, the concept of
      autopoiesis and its many consequences require significant further theoretical and
      empirical development. A crucial step in this direction is the formulation and
      analysis of models of autopoietic systems. This article sketches the beginnings
      of such a project by examining a glider from Conway's game of life in autopoietic
      terms. Such analyses can clarify some of the key ideas underlying autopoiesis and
      draw attention to some of the central open issues. This article also examines the
      relationship between an autopoietic perspective on cognition and recent work on
      dynamical approaches to the behavior and cognition of situated, embodied agents.

PMID- 15245631
TI  - Autopoiesis and cognition.
AB  - This article revisits the concept of autopoiesis and examines its relation to
      cognition and life. We present a mathematical model of a 3D tesselation
      automaton, considered as a minimal example of autopoiesis. This leads us to a
      thesis T1: "An autopoietic system can be described as a random dynamical system,
      which is defined only within its organized autopoietic domain." We propose a
      modified definition of autopoiesis: "An autopoietic system is a network of
      processes that produces the components that reproduce the network, and that also
      regulates the boundary conditions necessary for its ongoing existence as a
      network." We also propose a definition of cognition: "A system is cognitive if
      and only if sensory inputs serve to trigger actions in a specific way, so as to
      satisfy a viability constraint." It follows from these definitions that the
      concepts of autopoiesis and cognition, although deeply related in their
      connection with the regulation of the boundary conditions of the system, are not
      immediately identical: a system can be autopoietic without being cognitive, and
      cognitive without being autopoietic. Finally, we propose a thesis T2: "A system
      that is both autopoietic and cognitive is a living system."

PMID- 15245632
TI  - Autopoiesis and natural drift: genetic information, reproduction, and evolution
      revisited.
AB  - The contribution of the theory of autopoiesis to the definition of life and
      biological theory affirms biological autonomy as a central notion of scientific
      and philosophical inquiry, and opposes other biological approaches, based on the
      notion of genetic information, that consider reproduction and evolution to be the
      central aspects of life and living phenomenology. This article reviews the
      autopoietic criticisms of genetic information, reproduction, and evolution in the
      light of a biology that can solve the problem of living organization.

PMID- 15245633
TI  - The gift of mentoring.

PMID- 15245634
TI  - Comparison of symptoms of younger and older patients undergoing coronary artery
      bypass surgery.
AB  - Little is known about the symptom experience throughout the trajectory of
      recovery for patients after coronary artery bypass surgery (CABS). This study
      investigates the preoperative and postoperative symptoms experienced by younger
      (< 65 years) and older (> or = 65 years) patients (N= 102) who had undergone
      CABS. Reported preoperative symptoms were angina, shortness of breath, dizziness,
      and sweating. At 1 week post-CABS, symptoms were incisional pain, wound drainage,
      chest congestion, shortness of breath, dizziness, sweating, swollen feet, and
      loss of appetite; incisional pain and swollen feet were reported by a few
      patients at 6 weeks after CABS. The incidence and frequency of postoperative
      symptoms declined over time. There were several age-related differences in
      symptom reports prior to and at 1 and 6 weeks after the procedure. Such
      information can be used to plan the care of patients undergoing CABS, to prepare
      them for normal recovery, and to determine the need for symptom management by
      health care providers.

PMID- 15245636
TI  - An exploration of seniors' ability to report pain.
AB  - The purpose of this study was to evaluate the ability of a group of elderly
      residents to use self-report methods to measure their pain in an accurate
      fashion. Using a comparative descriptive design, completion rates of three pain
      assessment tools and the self-report skills of a sample of 130 long-term care
      residents with varying levels of cognitive impairment were evaluated. The
      majority of residents with mild to moderate cognitive impairment were able to
      complete at least one of the verbal pain assessment tools, with the Present Pain
      Intensity and Numerical Rating Scales being the preferred choices for use in
      clinical settings. However, the Faces Pain Scale appeared to be more challenging
      for residents to complete, suggesting that it requires further testing before it
      can be recommended for clinical use.

PMID- 15245637
TI  - Social support and positive health practices in early adolescents: a test of
      mediating variables.
AB  - This study examines the relationship between social support and positive health
      practices in early adolescents and tests two variables, loneliness and
      hopefulness, that theoretically mediate this relationship. The final sample of
      the study consisted of 134 adolescents, ages 12 to 14, who responded to
      instruments measuring social support, loneliness, hopefulness, and positive
      health practices in classroom settings. Correlational analysis supported the five
      hypothesized relationships. A series of regression analyses indicated that
      loneliness and hopefulness each were weak mediators of the relationship between
      social support and positive health practices. Implications for nursing practice
      are addressed.

PMID- 15245638
TI  - Use of a numeric visual analog anxiety scale among patients undergoing colorectal
      surgery.
AB  - The aim of this study was to evaluate the utility of a Numeric Visual Analog
      Anxiety Scale (NVAAS) as a potentially accurate and efficient way to determine
      presurgery anxiety among patients undergoing colorectal surgery. A secondary aim
      was to determine the relationship between NVAAS ratings of anxiety and
      postsurgery pain. Thirty-six patients scheduled for colorectal surgery were asked
      to rate their state anxiety on the NVAAS and to complete the State-Trait Anxiety
      Inventory (STAI). The NVAAS correlated significantly with STAI-state anxiety
      (0.64, p <.0001). The NVAAS measure of presurgery anxiety also correlated
      significantly with STAI-trait anxiety (0.46, p <.005) and postsurgery Visual
      Analog Scale pain ratings (0.35, p <.038). The NVAAS appears to be a valid and
      sensitive measure of anxiety among patients undergoing colorectal surgery. The
      NVAAS also has the advantage of being convenient and easy to use at bedside,
      increasing its clinical utility in medical nursing care.

PMID- 15245639
TI  - Physical fitness training: outcomes for adult oncology patients.
AB  - Physical activity and exercise participation are important considerations in the
      study and management of acute and long-term care for cancer patients. Although
      excessive rest and lack of physical activity are related to diminished physical
      fitness, reduced functional status, impaired cognition, and diminished quality of
      life, exercise prescription is not a standard treatment support for patients or
      survivors of cancer. In this retrospective study, it was hypothesized that
      routine participation in exercise could improve physical fitness for adults
      recently completing months of cancer treatment. Forty-five cancer patients were
      able to make considerable fitness gains over an 8-week period. A fitness program
      coordinated by an exercise physiologist, certified trainers, and an advanced
      practice cancer nurse was an effective method of organizing referral, monitoring
      individual patient concerns, and avoiding unnecessary risks.

PMID- 15245640
TI  - Release of silica, calcium, phosphorus, and fluoride from glass ionomer cement
      containing bioactive glass.
AB  - The aim of this study was to examine the release of silica (Si), calcium (Ca),
      phosphorous (P), and fluoride (F) from conventional glass ionomer cement (GI) and
      resin-modified glass ionomer cement (LCGI), containing different quantities of
      bioactive glass (BAG). Further aim was to evaluate in vitro biomineralization of
      dentine. The release of Si increased with the increasing immersion time from the
      specimens containing BAG, whereas the amount of Ca and P decreased indicating in
      vitro bioactivity of the materials. LCGI with 30wt% of BAG showed highest
      bioactivity. It also showed CaP-like precipitation on both the surface of the
      test specimens and on the dentin discs immersed with the material. Within the
      limitations of this study, it can be concluded that a dental restorative material
      consisting of glass ionomer cements and BAG is bioactive and initiates
      biomineralization on dentin surface in vitro.

PMID- 15245641
TI  - A novel use of genipin-fixed gelatin as extracellular matrix for peripheral nerve
      regeneration.
AB  - Application of combining herbal medicine and biomedical material science to nerve
      regeneration is a new approach. In this study, we describe a novel use of
      purified genipin, which can be extracted from Gardenia jasminoides Ellis, fixing
      the gelatin to be an extracellular matrix for peripheral nerve regeneration. A 10
      mm gap of rat sciatic nerve was created between the proximal and distal nerve
      stumps, which were sutured into silicone rubber tubes filled with either the
      genipin-fixed gelatin or collagen gel. Silicone rubber tubes filled with saline
      were used as controls. Six weeks after implantation, regeneration across the
      nerve gaps occurred in 80 and 90% of the animals from the groups of genipin-fixed
      gelatin and collagen, respectively, whereas only 30% in the control group. Large
      numbers of myelinated axons were also seen in the genipin-fixed gelatin (5104 +/-
      3278) and the collagen groups (8063 +/- 1807). These findings indicated that the
      genipin-fixed gelatin could be an acceptable extracellular matrix for nerve
      regeneration.

PMID- 15245642
TI  - Poly methacrylic acid-alginate semi-IPN microparticles for oral delivery of
      insulin: a preliminary investigation.
AB  - Microparticles of Poly methacrylic acid (P1) and novel semi-interpenetrating
      network composed of Poly methacrylic acid-alginate (P2) were prepared and their
      application in oral insulin delivery was evaluated. The microparticles were
      characterized by scanning electron microscopy (SEM) for morphological studies.
      Insulin loading onto the microparticles was performed by the diffusion filling
      method and insulin encapsulated microparticles were subjected to in vitro release
      study in buffer solution of pH 1.2 and 7.4. The release kinetics at pH 7.4
      exhibited sustained release of insulin for more than 5 h in case of PMAA
      microparticles whereas burst release of insulin (90% of total insulin loaded)
      within 1 h of study was observed in the case of PMAA-alginate microparticles. At
      pH 1.2, around 30% of insulin loaded was released from both microparticles within
      2 h of study.

PMID- 15245643
TI  - In vitro attachment of Staphylococcus epidermidis to surgical sutures with and
      without Ag-containing bioactive glass coating.
AB  - The ability of a silver-doped bioactive glass (AgBG) coating to prevent bacterial
      colonization on surgical sutures was investigated in vitro. Bioactive glass
      powders, in the form of 45S5 Bioglass and AgBG, were used to coat Mersilk sutures
      using an optimized 'in house' slurry-dipping process. In vitro experiments were
      carried out using Staphylococcus epidermidis under both batch and flow
      conditions. While the traditional batch culture testing was used to determine the
      number of viable cells adhered to the surface, the flow-cell was used to
      visualize attachment and detachment over time. Under batch conditions of up to
      180 min, statistically significant differences were observed in the colony
      forming units (CFU) per suture for both the coated and uncoated Mersilk sutures.
      The results showed that the AgBG coating had the greatest effect on limiting
      bacterial attachment (8 x 10(2) CFU) when compared to the 45S5 Bioglass coating
      (3.2 x 10(3) CFU) and the uncoated Mersilk (1.2 x 10(4) CFU). Also under flow
      conditions differences were seen between the coated and uncoated sutures.
      Therefore, this preliminary study has demonstrated the quantification and
      visualization of bacterial attachment onto sutures in order to compare the
      antibacterial properties of Ag-containing bioactive glass coatings. The
      bactericidal properties imparted by Ag-containing glass open new opportunities
      for use of the composite sutures in wound healing and body wall repair.

PMID- 15245644
TI  - Surface modification and characterization of chitosan film blended with poly-L
      lysine.
AB  - Biodegradable nerve guidance conduits (NGCs) represent a promising alternative to
      current clinical nerve repair procedures. Chitosan, a natural polysaccharide that
      has excellent biocompatibility and biodegradability, can be used as a nerve
      conduit material. The purpose of this work was to study the nerve cell affinity
      of chitosan modified by blending with different content of poly-L-lysine. PC12
      cells culture was used to evaluate the nerve cell affinity of the chitosan-poly-L
      lysine composite materials. The results showed that composite materials had
      significantly improved nerve cell affinity compared to chitosan as indicated by
      increased attachment, differentiation, and growth of nerve cells. The improved
      nerve cell affinity might be due to both the increased surface charge and
      hydrophilicity of composite materials. Composite material with 3 wt% poly-L
      lysine content (PL-3) is an even better material in nerve cell affinity than
      collagen, suggesting that poly-L-lysine-blended chitosan is a promising candidate
      material for nerve regeneration.

PMID- 15245645
TI  - You talking to me?

PMID- 15245646
TI  - The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland--a
      tale of conflict and resolution.
AB  - A theory is presented that explains the evolution of the pinealocyte from the
      common ancestral photoreceptor of both the pinealocyte and retinal photoreceptor.
      Central to the hypothesis is the previously unrecognized conflict between the two
      chemistries that define these cells-melatonin synthesis and retinoid recycling.
      At the core of the conflict is the formation of adducts composed of two molecules
      of retinaldehyde and one molecule of serotonin, analogous to formation in the
      retina of the toxic bis-retinyl ethanolamine (A2E). The hypothesis argues that
      early in chordate evolution, at a point before the genes required for melatonin
      synthesis were acquired, retinaldehyde--which is essential for photon capture-
      was depleted by reacting with naturally occurring arylalkylamines (tyramine,
      serotonin, tryptamine, phenylethylamine) and xenobiotic arylalkylamines. This
      generated toxic bis-retinyl arylalkylamines (A2AAs). The acquisition of
      arylalkylamine N-acetyltransferase (AANAT) prevented this by N-acetylating the
      arylalkylamines. Hydroxyindole-O-methyltransferase enhanced detoxification in the
      primitive photoreceptor by increasing the lipid solubility of serotonin and bis
      retinyl serotonin. After the serotonin --> melatonin pathway was established, the
      next step leading toward the pinealocyte was the evolution of a daily rhythm in
      melatonin and the capacity to recognize it as a signal of darkness. The shift in
      melatonin from metabolic garbage to information developed a pressure to improve
      the reliability of the melatonin signal, which in turn led to higher levels of
      serotonin in the photodetector. This generated the conflict between serotonin and
      retinaldehyde, which was resolved by the cellular segregation of the two
      chemistries. The result, in primates, is a pineal gland that does not detect
      light and a retinal photodetector that does not make melatonin. High levels of
      AANAT in the latter tissue might serve the same function AANAT had when first
      acquired- prevention of A2AA formation.

PMID- 15245647
TI  - A nitrate-induced frq-less oscillator in Neurospora crassa.
AB  - When nitrate is the only nitrogen source, Neurospora crassa's nitrate reductase
      (NR) shows endogenous oscillations in its nitrate reductase activity (NRA) on a
      circadian time scale. These NRA oscillations can be observed in darkness or
      continuous light conditions and also in a frq(9) mutant in which no functional
      FRQ protein is formed. Even in a white-collar-1 knockout mutant, NRA oscillations
      have been observed, although with a highly reduced amplitude. This indicates that
      the NRA oscillations are not a simple output rhythm of the white-collar-driven
      frq oscillator but may be generated by another oscillator that contains the nit-3
      autoregulatory negative feedback loop as a part. In this negative feedback loop,
      a product in the reaction chain catalyzed by nitrate reductase, probably
      glutamine, induces repression of the nitrate reductase gene and thus
      downregulates its own production. This is the first example of an endogenous,
      nutritionally induced daily rhythm with known molecular components that is
      observed in the absence of an intact FRQ protein.

PMID- 15245648
TI  - Light pulses do not induce c-fos or per1 in the SCN of hamsters that fail to
      reentrain to the photocycle.
AB  - Circadian activity rhythms of most Siberian hamsters (Phodopus sungorus sungorus)
      fail to reentrain to a 5-h phase shift of the light-dark (LD) cycle. Instead,
      their rhythms free-run at periods close to 25 h despite the continued presence of
      the LD cycle. This lack of behavioral reentrainment necessarily means that
      molecular oscillators in the master circadian pacemaker, the SCN, were unable to
      reentrain as well. The authors tested the hypothesis that a phase shift of the LD
      cycle rendered the SCN incapable of responding to photic input. Animals were
      exposed to a 5-h phase delay of the photocycle, and activity rhythms were
      monitored until a lack of reentrainment was confirmed. Hamsters were then housed
      in constant darkness for 24 h and administered a 30-min light pulse 2 circadian
      hours after activity onset. Brains were then removed, and tissue sections
      containing the SCN were processed for in situ hybridization. Sections were probed
      with Siberian hamster c-fos and per1 mRNA probes because light rapidly induces
      these 2 genes in the SCN during subjective night but not at other circadian
      phases. Light pulses induced robust expression of both genes in all animals that
      reentrained to the LD cycle, but no expression was observed in any animal that
      failed to reentrain. None of the animals exhibited an intermediate response. This
      finding is the first report of acute shift in a photocycle eliminating
      photosensitivity in the SCN and suggests that a specific pattern of light
      exposure may desensitize the SCN to subsequent photic input.

PMID- 15245649
TI  - Genetic analyses of a seasonal interval timer.
AB  - Seasonal clocks (e.g., circannual clocks, seasonal interval timers) permit
      anticipation of regularly occurring environmental events by timing the onset of
      seasonal transitions in reproduction, metabolism, and behavior. Implicit in the
      concept that seasonal clocks reflect adaptations to the local environment is the
      unexamined assumption that heritable genetic variance exists in the critical
      features of such clocks, namely, their temporal properties. These experiments
      quantified the intraspecific variance in, and heritability of, the
      photorefractoriness interval timer in Siberian hamsters (Phodopus sungorus), a
      seasonal clock that provides temporal information to mechanisms that regulate
      seasonal transitions in body weight. Twenty-seven families consisting of 54
      parents and 109 offspring were raised in a long-day photoperiod and transferred
      as adults to an inhibitory photoperiod (continuous darkness; DD). Weekly body
      weight measurements permitted specification of the interval of responsiveness to
      DD, a reflection of the duration of the interval timer, in each individual. Body
      weights of males and females decreased after exposure to DD, but 3 to 5 months
      later, somatic recrudescence occurred, indicative of photorefractoriness to DD.
      The interval timer was approximately 5 weeks longer and twice as variable in
      females relative to males. Analyses of variance of full siblings revealed an
      overall intraclass correlation of 0.71 +/- 0.04 (0.51 +/- 0.10 for male offspring
      and 0.80 +/- 0.06 for female offspring), suggesting a significant family
      resemblance in the duration of interval timers. Parent-offspring regression
      analyses yielded an overall heritability estimate of 0.61 +/- 0.2; h(2) estimates
      from parent-offspring regression analyses were significant for female offspring
      (0.91 +/- 0.4) but not for male offspring (0.35 +/- 0.2), indicating strong
      additive genetic components for this trait, primarily in females. In nature,
      individual differences, both within and between sexes, in the timekeeping
      properties of seasonal interval timers, and a strong heritable basis thereof,
      would provide ample substrate for selection to rapidly influence seasonal clocks.
      Balancing selection in environments where the onset of spring conditions varies
      from year to year could maintain genetic variance in interval timers and yield
      interval timers tuned to the local environment.

PMID- 15245650
TI  - Effect of circadian phase on performance of rats in the Morris water maze task.
AB  - The authors examined spatial working memory in the Morris water maze during the
      activity and rest periods of Wistar rats. Wheel-running activity was measured
      continuously as a marker of circadian phase. To minimize possible masking effects
      on performance, animals were placed in constant dim light the day before testing
      and tested in similar light conditions. Three experiments were run, each of them
      using animals varying in their previous experience in the water maze. Half of the
      animals of each experiment were tested 2 to 3 h after activity onset (active
      group), and the other half were tested 14 to 15 h after activity onset (inactive
      group). In the three experiments, a significant phase effect was observed in the
      animals' performance in the water maze; animals tested in the active phase showed
      steeper acquisition curves. These phase effects on performance are due to the
      animals' search pattern and not to a better acquisition and maintenance of
      spatial information; rats tested in the inactive phase found the platform faster
      on the first trial of the test, when the information on the location of the
      platform had not been presented to the animals. This effect vanished as the
      amount of training in the pool increased. Finally, swimming speed also showed a
      temporal effect, suggesting the existence of a phase effect for motivation to
      escape from the water; rats tested during their inactive phase tended to swim
      faster. All together, the data suggest a modulating effect of the biological
      clock on performance in the water maze, particularly when the animals are less
      experienced.

PMID- 15245651
TI  - Effects of moonlight exposure on plasma melatonin rhythms in the seagrass
      rabbitfish, Siganus canaliculatus.
AB  - Influences of light-dark (LD) cycle and moonlight exposure on plasma melatonin
      rhythms in the seagrass rabbitfish, Siganus canaliculatus, a lunar synchronized
      spawner, were determined by time-resolved fluoroimmunoassay (TR-FIA). When the
      fish were exposed to a natural LD (12:12) cycle, plasma melatonin levels
      exhibited a clear daily rhythm, with higher levels at midnight and lower levels
      during the day. These rhythms were not evident under either constant light (LL)
      or constant dark (DD) conditions. Plasma melatonin levels under LL condition were
      low and high under DD condition. These results indicate that plasma melatonin
      rhythms are driven by LD cycle in this species. When the fish were exposed to the
      4 lunar phases, plasma melatonin levels around the new moon were significantly
      higher than during the first quarter moon and the full moon. Exposure to
      experimental new moon and full moon conditions caused significant increases and
      decreases of plasma melatonin levels, respectively. The synchronous rhythmicity
      of melatonin levels in the plasma support the hypothesis that the seagrass
      rabbitfish perceives moonlight intensity and responds with secretion of melatonin
      into the bloodstream.

PMID- 15245652
TI  - Editorial: Brian Mitchell--religious insanity and the law.

PMID- 15245653
TI  - An exploratory examination of the Spiritual Well-Being Scale among incarcerated
      black and white male drug users.
AB  - A number of studies have examined the link between criminality and religiosity.
      However, only a limited number of studies have examined the relationship between
      spirituality and criminality. Because spirituality has been identified as a
      fundamental attribute of the personalities of Blacks, studies examining
      differences in the association between spirituality by ethnicity could provide
      information to understand the disparity of incarceration rates among Blacks and
      Whites. For this study, data were collected from 661 male prisoners with prior
      histories of drug use to examine spirituality that was assessed using two factors
      from a modified version of the Spiritual Well-Being Scale: relationship with a
      higher power and satisfaction with oneself in the world. Analyses revealed that
      White men reported significantly higher scores on both factors than Black men.
      The unexpected findings are discussed in light of the existing literature that
      identifies the significance of spirituality in the personality and coping style
      of Blacks.

PMID- 15245654
TI  - Muslims in prison: a case study from Ohio state prisons.
AB  - The present study explores core issues related to the understudied population of
      Muslim inmates. Mail questionnaires were sent to the full-time chaplains employed
      by religious services in thirty Ohio state male prisons. The survey examines: (1)
      characteristics of Muslim inmates, (2) patterns of identification with Islam, (3)
      religious behavior inside the prisons, and (4) relations between conversion to
      Islam and crime committed. Our findings indicate that while the vast majority of
      Muslim inmates are African-American, they are otherwise similar to the
      incarcerated population in terms of age, education, and marital status. Most of
      the Muslims in our sample converted while incarcerated. The devotion of Muslim
      prisoners in the sample tends to be high as demonstrated by adherence to central
      religious practices. Finally, we found no relationship between crime and
      conversion to Islam inside prison. Although our data must be understood as
      tentative, it offers a basis for further investigation of this population of
      inmates.

PMID- 15245655
TI  - The role of religiosity in the opposition to drug use.
AB  - This study examines the causal mechanism linking religiosity to opposition to
      drug use. Using an electronic mail survey of university students, data were
      obtained about the participants' religious beliefs, their perceptions of drug
      use, and their attitudes toward the use of six common drugs (alcohol, cigarettes,
      cocaine, heroin, LSD, and marijuana). Based on the data, path models were
      estimated for each substance to investigate the causal structure underlying four
      constructs: religiosity, perceived immorality of drug use, perceived self-harm of
      drug use, and attitudes toward the control of drug use (control attitudes). The
      results support that religiosity affects control attitudes indirectly through
      perceived immorality of drug use.

PMID- 15245656
TI  - American social work, corrections and restorative justice: an appraisal.
AB  - Social work played an active role in American corrections until the 1980s when
      the ethic of rehabilitation began to give way to a more conservative doctrine of
      retribution. Changes in the field of social work, characterized by preference of
      social workers to work only with certain populations, contributed to social
      work's diminishment in corrections. Although efforts at rehabilitation continue
      in corrections, the concept of restorative justice that emphasizes assisting
      victims, communities, and offenders in dealing with the consequences of crime is
      gaining acceptance in the field of corrections in the United States and in other
      countries. This study explored social work's presence in corrections, the decline
      of that presence, and how the concept of restorative justice can invigorate
      social work within the field of corrections. Several examples of social work's
      contemporary efforts to use the concept of restorative justice in the United
      Kingdom are presented.

PMID- 15245657
TI  - Applying social learning theory to childhood and adolescent firesetting: can it
      lead to serial murder?
AB  - Despite the fact that serial murder has existed for centuries, it has been given
      little academic attention in the social science literature. Existing studies have
      primarily examined the motivational factors involved in the commission of serial
      murder. However, research examining the childhood and adolescent backgrounds of
      serial murderers is scant. Based on three case studies of serial murderers, this
      study contributes to the existing literature by exploring the possible link
      between childhood and/or adolescent fire setting and adult serial murder by
      applying social learning theory.

PMID- 15245658
TI  - Believing is seeing III: perceptions of content in criminal psychological
      profiles.
AB  - This study explored Kocsis and Heller's findings concerning the relationship
      between one's belief and the perceived accuracy of a profile. The influence of
      types of information was also considered. A sample of 353 participants was used
      in the present experiment that gauged the perception of information contained in
      a profile. The results supported Kocsis and Heller's earlier findings with a
      positive relationship found between belief and perceived accuracy. The more an
      individual believes in profiling, the more likely he or she is to perceive a
      profile to be accurate. This relationship was most pronounced in participants'
      perceptions of information contained in a profile concerning an unknown
      offender's crime behavior and past history. The more an individual believes in
      profiling, the more information relating to these two factors is likely to be
      perceived. This relationship was not observed where information in the same
      profile involved physical features of the offender.

PMID- 15245659
TI  - A neural network applied to criminal psychological profiling: an Italian
      initiative.
AB  - The author presents a brief discussion of criminal profiling followed by an
      introduction to the Italian Neural Network for Psychological Criminal Profiling
      (NNPCP) project. This project, based on a so-called neural network and data
      mining, is an innovative technique being developed with the intention of
      extending criminal profiling to single serious crimes through the use of a
      computerized database.

PMID- 15245660
TI  - Social climate within an adolescent medium-secure facility.
AB  - The objectives of the study were to investigate the social climate of two
      different types of units (open vs. secure) contained within the same South London
      adolescent medium-secure facility. Two hypotheses were generated: (a) adolescents
      would rate the social climate of the whole facility in a more negative direction
      than staff and (b) adolescents and staff would rate the social climate of the
      open units in a more positive direction than the social climate of the secure
      units. 43 adolescents and 49 staff members from the open units and the secure
      units were recruited and completed the Correctional Institutions Environment
      Scale (CIES), a measure of social climate. Overall, adolescents tended to rate
      the facility in a more negative direction. All participants rated the open units
      in a more positive direction than secure units. However, on selected subscales
      there were differences. The findings of this study suggest that adolescents and
      staff may perceive their shared social climate differently. This may have
      implications for those attempting to develop positive social climates within
      secure services.

PMID- 15245661
TI  - Initial experience with the four-arm computer-enhanced telesurgery device in
      foregut surgery.
AB  - BACKGROUND: The da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA) has
      been used effectively and with good results. Previously, the surgeon could
      manipulate three arms on the robot: one camera port and two working ports. This
      configuration required a second surgeon for most general surgical procedures.
      Recently, the robotic device has been modified to include a fourth arm, adding
      another computer-assisted instrument that the surgeon can manipulate. In this
      report, we describe our experience with the da Vinci robot with a fourth arm
      modification for the performance of selected surgical procedures. MATERIALS AND
      METHODS: A total of six patients were prospectively enrolled and underwent
      surgery using the modified da Vinci robot. Their average age was 56 years. Five
      patients underwent Nissen fundoplication, and one patient underwent Heller
      myotomy. Operative time, defined as the time from skin incision to completed skin
      closure, as well as robotic time, defined as the time during which the robot was
      being used, were recorded. Intra-operative and perioperative complications were
      also recorded. RESULTS: Average operative and robotic times for Nissen
      fundoplication were 134 and 80 minutes, respectively. Operative and robotic times
      for the Heller myotomy were 118 and 70 minutes. All patients tolerated the
      procedure well and experienced no perioperative complications. CONCLUSIONS: The
      da Vinci robot with the addition of the fourth arm results in a efficient and
      safe operation and allows the surgeon to perform additional maneuvers without the
      use of a surgical assistant.

PMID- 15245662
TI  - Irrigation of port sites: prevention of port site metastases?
AB  - INTRODUCTION: Port site metastases can occur when free viable tumor cells implant
      at trocar wounds. Irrigation of port sites with cytotoxic agents has been
      suggested to prevent port site metastases. The objective of this study is to
      assess whether tumor growth at port sites can be reduced by irrigation of these
      port sites. METHODS: WAG rats were insufflated with CO(2) for 20 minutes and 5 x
      10(5) CC531 tumor cells were injected intraperitoneally. Port sites were
      irrigated after completion of the pneumoperitoneum with povidone-iodine, a
      mixture of taurolidine and heparin, or sodium chloride. Controls did not undergo
      any irrigation of port sites. In experiment 1, all 16 rats had all 4 irrigation
      modalities. In experiment 2, four groups of 20 rats had one type of irrigation on
      two trocar wounds. Tumor growth was evaluated 4 weeks after the procedure.
      RESULTS: No difference in tumor growth at trocar wounds was found between any
      type of irrigation and controls in both experiments. CONCLUSION: In this
      experimental model, no beneficial or adverse effects of irrigation of port sites
      could be shown.

PMID- 15245663
TI  - Laparoscopic biliopancreatic diversion with distal gastric preservation:
      technique and three-year followup.
AB  - BACKGROUND: Biliopancreatic diversion (BPD) has been used satisfactorily as one
      of several surgical treatments against morbid obesity in order to achieve long
      term weight reduction. Our goal was to develop the BPD laparoscopically in humans
      in order to improve postoperative recovery and to reduce early and late
      complications, above all those derived from the abdominal wall, while maintaining
      the weight reduction results achieved. In addition, in order to reduce the
      laparoscopic difficulty of BPD technique and some complications associated with
      gastrectomy, we only carried it out in cases in which we considered it
      indispensable. PATIENTS AND METHODS: Since October 2000 we have performed 50
      laparoscopic BPD with distal gastric preservation (39 women and 11 men). We
      preserve the distal stomach if the upper digestive endoscopy with biopsy does not
      show pathological findings. RESULTS: Two operations (within the first ten cases)
      were converted to open surgery. The average operating time was 177.7 minutes
      (range, 110-360 minutes). There were no immediate postoperative complications.
      There was no postoperative mortality. CONCLUSION: It has been proven that BPD can
      be performed satisfactorily using laparoscopy, but this technique requires a very
      skilled and experienced laparoscopic surgeon. Avoiding gastrectomy is a very
      interesting option in order to reduce technical difficulties, surgeon stress,
      duration of the operation, patient stress, and, probably, postoperative morbidity
      and mortality. Laparoscopic BPD with distal gastric preservation is a very
      promising bariatric procedure with potential advantages over laparoscopic BPD
      with gastrectomy or open BPD.

PMID- 15245664
TI  - Laparoscopic-assisted vaginal myomectomy through an anterior approach.
AB  - BACKGROUND: To evaluate the safety and efficacy of a combined laparoscopic and
      vaginal approach through the anterior cul-de-sac in dealing with fundal and/or
      anterior wall uterine myomata. PATIENTS AND METHODS: Seven women with symptomatic
      fundal and/or anterior wall uterine myomata were enrolled in this study. After
      laparoscopic identification of the location of the myomata, a guiding suture
      brought the dominant myoma down through the anterior cul-de-sac into the vagina
      via an anterior colpotomy. Resection and suturing were then performed
      transvaginally. RESULTS: Mean +/- standard deviation (SD) operative time, blood
      loss, and the length of hospital stay were 88.1 +/- 27.8 minutes, 278.6 +/- 131.8
      mL, and 2.9 +/- 0.7 days, respectively. No patients developed serious
      complications, and only four transient macroscopic hematuria occurred intra- and
      postoperatively. CONCLUSION: Although transient hematuria may occur, a combined
      laparoscopy and vaginal approach in dealing with fundal and/or anterior wall
      uterine fibroids through the anterior cul-de-sac is an alternative to pure
      laparoscopic myomectomy.

PMID- 15245665
TI  - A reappraisal of the indications for laparoscopic treatment of adrenal
      metastases.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) is unanimously recognized as the gold
      standard for the surgical treatment of adrenal lesions, but when to remove
      malignant lesions by this approach still remains controversial. STUDY DESIGN: We
      reviewed all cases of LA for suspected adrenal metastases carried out in our
      hospital, trying to focus on what should be the ideal preoperative workup, so as
      to avoid unnecessary operations. The possible role of fine needle aspiration
      biopsy (FNAB) in selecting patients was evaluated. RESULTS: Twenty-two patients
      underwent LA for suspected adrenal metastases from May 1994 to March 2003.
      Primary tumors were from lung in 14 cases, colon in 2 cases, kidney in 3 cases,
      thyroid in 2 cases, and breast in 1 case. LA was successfully performed in all
      but three cases. In 13 patients, 14 FNAB were performed: 8 cases proved to be
      true positive, 4 true negative, and 2 false negative. Final histology showed 6
      cortical adenomas. Local relapse was present only in one patient, who died after
      14 months. Of the metastatic patients, 8 are alive and free of disease after a
      mean followup of 39 months. CONCLUSIONS: The most accurate workup is of the
      greatest importance in order to avoid unnecessary surgery for suspected adrenal
      metastases. The absence of false positives (FP) and the fairly high number of
      true positives (TP) does not justify the effort of performing FNAB routinely.
      Indeed, laparoscopic exploration, being simple and quick, allows optimal
      diagnosis at a low cost, even when histological definition cannot be obtained.

PMID- 15245666
TI  - Can endoscopic injection of epinephrine prevent surgery in gastroduodenal ulcer
      bleeding? An analysis of 107 cases.
AB  - BACKGROUND: Gastroduodenal ulcers are still a common cause of severe upper
      gastrointestinal bleeding. Endoscopy has gained popularity worldwide over
      conventional open surgery for the treatment of upper gastrointestinal bleeding.
      This study aims to assess the efficacy of endoscopic injection of epinephrine in
      the treatment of gastroduodenal ulcer bleeding. METHODS: This study was conducted
      between March 2000 and March 2003. We analyzed 107 consecutive patients admitted
      to our department of trauma and emergency surgery with upper gastrointestinal
      bleeding. Endoscopy was performed on all 107 patients and bleeding ulcers were
      treated with injection of diluted epinephrine. RESULTS: Recurrent bleeding was
      seen in 21 patients (19.6%), all of whom underwent a second endoscopy. Four
      patients (3.7%) required a third endoscopy session and nine patients (8.5%)
      needed surgery after endoscopy failed. There were two mortalities (1.9%). The
      nine patients who required surgery and the two patients who died were all in the
      Forrest Ia and Ib groups of acute UGI hemorrhage. DISCUSSION: Endoscopic
      injection therapy with epinephrine reduces operation rates and can be used safely
      in adequate hemostasis of gastroduodenal ulcers.

PMID- 15245667
TI  - Endo-GIA for ligation of dilated cystic duct during laparoscopic cholecystectomy:
      an alternative, novel, and easy method.
AB  - BACKGROUND: This study prospectively assessed the efficacy and applicability of
      Endo-GIA for difficult and dilated cystic duct (CD) closure in 24 patients
      undergoing laparoscopic cholecystectomy (LC) due to CD stone. METHODS: From
      January 1998 to December 2002, 3325 patients underwent LC for gallbladder lesions
      at the department of general surgery at Chang Gung Memorial Hospital (Taipei,
      Taiwan), and 24 (0.72%) were identified as having dilated and difficult CD, which
      were ligated by Endo-GIA. This study prospectively followed these 24 patients and
      evaluated the management outcomes. The indications for LC in the 24 patients were
      symptomatic gallstones with or without common bile duct (CBD) stones (11
      patients), Mirizzi syndrome type I (two patients), acute cholecystitis (five
      patients), acute cholecystitis with acute cholangitis (two patients), acute
      cholangitis (one patient), biliary pancreatitis (two patients), and gallbladder
      polyp (one patient). RESULTS: No patients required conversion to open surgery.
      The CD were successfully ligated with Endo-GIA in all 24 patients with dilated
      and difficult CD during LC. The postoperative course was uneventful except in two
      patients. One patient suffered bile duct injury (Stewart-Way class II), and was
      managed successfully by repeated endoscopic stent. The other case was complicated
      with retained CBD stone due to migration of fragmented CD stone and was managed
      by endoscopic papillotomy and stone retrieval. Followup ranged from 1 to 40.2
      months (median, 18.5 months) and no other complications were discovered during
      the followup period. CONCLUSIONS: Endo-GIA is a safe and effective procedure for
      closing dilated and difficult CD. Endo-GIA could alternatively be attempted in
      other selected cases because of its ease of application.

PMID- 15245668
TI  - Outcome and cost comparison of laparoscopic transabdominal preperitoneal hernia
      repair versus Open Lichtenstein technique.
AB  - Laparoscopic hernia repair has all the advantages of a tension free repair. This
      study compares the laparoscopic transabdominal preperitoneal (TAPP) approach with
      tension-free open hernia repair in terms of operative time, postoperative pain,
      hospital stay, complications, and cost. Open and TAPP repairs using polypropylene
      mesh were performed in two groups of 25 male patients. The difference in
      operative times between the groups was not significant. Mean pain scores (0-100)
      for the open group were 54.12 +/- 13.06 at 12 hours and 37.24 +/- 11.38 at 24
      hours, significantly higher than the corresponding scores of 38.36 +/- 8.21 at 12
      hours and 20.92 +/- 8.73 at 24 hours for the TAPP group (P < 0.05). The mean
      postoperative analgesic dose was 6.72 +/- 2.72 in the TAPP group, which was
      insignificantly lower than 7.52 +/- 2.00 in the open group. Mean hospital stay
      was 2.24 +/- 0.97 days in the open group and 1.52 +/- 0.51 in the TAPP group,
      which was significant (P < 0.05). Twenty patients (80%) in the TAPP group rated
      themselves highly satisfied with the surgery as compared to 11 patients (44%) in
      the open group (P < 0.05). There was no recurrence in either group during a mean
      followup period of 13.5 months (range, 8-28 months). Laparoscopic hernia repair
      was significantly more expensive than open (1100 US dollars versus 629 US
      dollars). TAPP repair is superior to open repair in terms of shorter hospital
      stay, lower postoperative pain, and better patient satisfaction. It is also safe,
      with no recurrence in a short-term period. This technique will be the operation
      of choice for the treatment of groin hernia after long-term results have been
      established in our center.

PMID- 15245669
TI  - The comparison of the oxidative stress effects of different gases and intra
      abdominal pressures in an experimental rat model.
AB  - BACKGROUND: Laparoscopy is used for almost all types of abdominal surgery because
      of its advantages, which include shorter postoperative hospital stay. However,
      pneumoperitoneum used to facilitate the visual field has severe metabolic,
      hemodynamic, and inflammatory consequences depending on the pressure level and
      the gas used. Helium (He), an inert gas, has been recommended for establishment
      of pneumoperitoneum since it does not alter the blood pH and PCO(2). Yet the
      oxidative response after He insufflation remains unknown. This study was
      undertaken to compare the levels of free radical production and antioxidant
      status following He and CO(2) pneumoperitoneum at different intra-abdominal
      pressure values. MATERIALS AND METHODS: The subjects were 40 Sprague-Dawley male
      rats randomized to the following groups: He 10 (n = 8) was subjected to He
      pneumoperitoneum at 10 mm Hg for 60 minutes; He 15 (n = 8) was subjected to He
      pneumoperitoneum at 15 mm Hg for 60 minutes; CO(2) 10 (n = 8) was subjected to
      CO(2) pneumoperitoneum at 10 mm Hg for 60 minutes; CO(2) 15 (n = 8) was subjected
      to CO(2) pneumoperitoneum at 15 mm Hg for 60 minutes; and Control (n = 8) was
      subjected to sham operation without pneumoperitoneum. At the end of the
      experiment blood samples were obtained and plasma malondialdehyde, carbonyl, and
      sulphydryl levels were measured. RESULTS: CO(2) pneumoperitoneum produced higher
      malondialdehyde and carbonyl responses and sulphydryl consumption compared to He,
      especially at 15 mm Hg (P = 0.01, P = 0.01, and P = 0.059, respectively).
      CONCLUSION: Helium seems to limit the postoperative oxidative response following
      laparoscopy.

PMID- 15245670
TI  - Endoscopic hemostasis for bleeding gastric stromal tumors by application of
      hemoclip.
AB  - In the past, numerous reports have advocated primary surgical resection as a
      treatment of choice for bleeding gastric stromal tumors (GIST). There were scarce
      reports on primary hemostasis with endoscopic therapy. We encountered two
      patients who presented to our unit with acute bleeding from gastric fundal
      stromal tumor, in whom we were able to achieved successful endoscopic hemostasis
      with hemoclip therapy. We describe the management of these cases and reviewed the
      current management strategies in bleeding gastric stromal tumor.

PMID- 15245671
TI  - Spleen-preserving laparoscopic distal pancreatectomy after division of the
      splenic vessels.
AB  - A 37-year-old woman with a history of syncope was hospitalized with a diagnosis
      of hypoglycemia due to insulinoma. Computed tomography (CT) and magnetic
      resonance imaging revealed an enhanced solid mass, 1.5 cm in diameter, at the
      tail of the pancreas. Angiography via the splenic artery revealed a hypervascular
      mass. Because the tumor was located deep in the pancreatic parenchyma,
      laparoscopic distal pancreatectomy was performed. The pancreas was exposed by
      dissecting the greater omentum, and the tumor was located by intraoperative
      ultrasonography. After division of the splenic artery, the pancreas, main
      pancreatic duct, and splenic vein were transected with an endoscopic linear
      stapler. The pancreatic pedicle was divided at the splenic hilum to preserve the
      spleen. The postoperative course was uneventful except for the appearance of
      splenic infarction on a CT scan 2 weeks after surgery but without any overt
      symptoms. Spleen-preserving laparoscopic distal pancreatectomy by division of
      splenic vessels is a feasible treatment option for benign pancreatic disease.

PMID- 15245672
TI  - Simultaneous laparoscopic radical nephrectomy and laparoscopic sigmoidectomy for
      synchronous renal cell carcinoma and colonic adenocarcinoma.
AB  - Hand-assisted laparoscopic radical nephrectomy is an established therapeutic
      choice for localized renal cell carcinoma. Laparoscopic sigmoidectomy is becoming
      accepted for the treatment of locally advanced sigmoid colon cancer. Primary
      cancer may occur synchronously in two different organs, in which case
      simultaneous resection is recommended if possible. To our knowledge this is the
      first report of simultaneous laparoscopic resection of coexistent renal and
      colonic double primary malignant tumors.

PMID- 15245673
TI  - Laparoscopic varicocelectomy with lymphatic preservation using methylene blue
      dye.
AB  - A novel technique is described herein to perform a laparoscopic varicocelectomy
      using the high-ligation modified Palomo technique. The variation in this case is
      the preservation of lymphatic drainage by intraoperative identification of the
      lymphatics using intratesticular injection of methylene blue dye.

PMID- 15245674
TI  - Laparoscopic revision of gastric pacing wires.
AB  - Currently, electrical stimulation is utilized to treat morbid obesity,
      gastroparesis, and diaphragmatic paralysis. Although this technology is in its
      infancy, numerous case reports and small series appear throughout the literature.
      Furthermore, electrical stimulation is not relegated to only academic centers and
      tertiary referral centers. As these technologies continue to evolve and alter the
      treatment of several different pathophysiologic processes, the general surgeon
      needs to understand the technical aspects of these devices and their potential
      complications. This paper presents the management of a gastroparetic patient with
      chronic abdominal pain following the successful placement of gastric pacing
      wires. A 45-year-old female with idiopathic gastroparesis underwent laparoscopic
      placement of gastric pacing wires without complications. Four months
      postoperatively, she presented with chronic left upper quadrant abdominal pain.
      Her nausea and vomiting had dissipated and she was tolerating a regular diet.
      Abdominal and pelvic computed tomography (CT) was normal except for the presence
      of a generator and pacing wires. Ultimately, she required a diagnostic
      laparoscopy and an upper endoscopy. The upper endoscopy was normal. The
      diagnostic laparoscopy showed a wide adhesive band from the seromuscular tunnel
      of the pacing wires to the abdominal wall in the left upper quadrant. The band
      was lysed and an omental patch was sutured over the insertion site of the wires.
      On postoperative day 1, the patient was pain-free and discharged home on a
      regular diet. This case presents an unusual complication of electrical pacing
      wires. This patient experienced somatic pain due to an adhesive band from her
      pacing wires to the abdominal wall. Based on the findings of this case, an
      omental patch was placed on top of the seromuscular electrode tunnel in order to
      prevent adhesions and potentially persistent abdominal wall pain.

PMID- 15245675
TI  - Application of haptic feedback to robotic surgery.
AB  - Robotic surgical systems have greatly contributed to the advancement of minimally
      invasive endoscopic surgery. However, current robotic systems do not provide
      tactile or haptic feedback to the operating surgeon. Under certain circumstances,
      particularly with the manipulation of delicate tissues and suture materials, this
      may prove to be a significant irritation. We hypothesize that haptic feedback, in
      the form of sensory substitution, facilitates the performance of surgical knot
      tying. This preliminary study describes evidence that visual sensory substitution
      permits the surgeon to apply more consistent, precise, and greater tensions to
      fine suture materials without breakage during robot-assisted knot tying.

PMID- 15245676
TI  - Childhood sexual abuse: a gender perspective on context and consequences.
AB  - Literature on gender and child sexual abuse (CSA) has highlighted patterns of
      similarity and difference among survivors and the need for further research. This
      study relied on gender analysis of 128 women and 69 men, obtained through an
      examination of childhood hospital records, to further examine gender differences
      in mental health outcomes among abuse survivors and correlates of mental health
      outcomes including professional help seeking, family environment, and other
      trauma exposure. Overall, men and women were similar in the context and
      consequences of CSA. The role of the characteristics of CSA and contextual
      variables in explaining variance in mental health for 106 male victims and
      nonvictims was also examined. Among male participants, number of incidents of
      sexual abuse, injury at the hands of a caregiver, and exposure to other traumas
      significantly explained higher levels of an array of mental health symptoms.
      Implications for future research are discussed.

PMID- 15245677
TI  - Assessing sexual behavior in high-risk adolescents with the adolescent clinical
      sexual behavior inventory (ACSBI).
AB  - This study examined the reliability and validity of the Adolescent Clinical
      Sexual Behavior Inventory (ACSBI), a new 45-item measure, designed to elicit
      parent-and self-report regarding a range of sexual behaviors in high-risk
      adolescents. Using this measure, this study also investigated predictors of
      adolescent sexual behavior. Participants were 174 adolescents and their parents
      consecutively admitted to one of three clinical settings (i.e., inpatient
      treatment, partial hospital program, and outpatient clinic). Parent-and self
      reports of adolescent sexual behavior were moderately correlated, and there was a
      strong relationship between high-risk sexual behavior and adolescent emotional
      and behavioral problems, as well as sexual concerns, distress, and preoccupation.
      In addition to sexual abuse, physical abuse, life stress, and impaired family
      relationships also significantly predicted sexual behavior in adolescents.

PMID- 15245678
TI  - Challenging children in kin versus nonkin foster care: perceived costs and
      benefits to caregivers.
AB  - This study uses social exchange theory as a framework for examining 102 kin and
      157 nonkin foster parents' perceptions of their foster children, their
      relationships with them, and their own functioning. The authors argue that these
      perceptions reflect perceived costs and benefits of parenting these children,
      which may influence their investment in them. All children in the study were
      referred to Parent-Child Interaction Therapy (PCIT) for treatment of the
      children's behavior problems, participating with their foster parents. Analyses
      showed that nonkin caregivers rated their foster children's behavior problems as
      significantly more severe than kin caregivers but rated themselves as
      significantly less stressed. Analyses predicting early treatment termination
      showed that kin caregivers were more likely than nonkin caregivers to complete
      the course of treatment in PCIT, particularly if they reported elevated levels of
      parental distress. The authors discuss the implications of these findings for
      foster children's placement stability and long-term success.

PMID- 15245679
TI  - Legal outcomes for children who have been sexually abused: the impact of child
      abuse assessment center evaluations.
AB  - Fifty children who were seen at a Child Abuse Assessment Center (CAAC) were
      matched on age and relationship to perpetrator with 51 children not evaluated at
      a CAAC to determine whether the groups differed in legal outcomes in cases of
      sexual abuse. CAAC children were significantly more likely to have cases filed
      rather than no-actioned, to have more overall counts charged in filed cases, to
      have more counts charged against biological fathers and stepfathers who were
      alleged perpetrators, and to have a greater number of defendants pleading or
      being found guilty compared to cases involving children not seen at the CAAC.
      There were also significantly more cases filed for 4- to 6-year-olds and children
      at least 12 years old if they were seen at the CAAC. The implications of the
      results are discussed in light of the use of CAACs.

PMID- 15245680
TI  - The effects of early prevention programs for families with young children at risk
      for physical child abuse and neglect: a meta-analysis.
AB  - In this article, a meta-analysis is presented on 40 evaluation studies of early
      prevention programs for families with young children at risk for physical child
      abuse and neglect with mostly nonrandomized designs. The main aim of all programs
      was to prevent physical child abuse and neglect by providing early family
      support. For the meta-analysis, a multilevel approach was used. A significant
      overall positive effect was found, pointing to the potential usefulness of these
      programs. The study demonstrated a significant decrease in the manifestation of
      abusive and neglectful acts and a significant risk reduction in factors such as
      child functioning, parent-child interaction, parent functioning, family
      functioning, and context characteristics.

PMID- 15245681
TI  - How does trauma beget trauma? Cognitions about risk in women with abuse
      histories.
AB  - This study examined the associations between perceived risks and benefits of drug
      use, unsafe sexual behavior, alcohol consumption, and aggressive/illegal behavior
      and reports of expected involvement in those behaviors in a sample of 340 college
      women with and without histories of interpersonal victimization (i.e., child
      sexual abuse, child physical abuse, adult sexual assault, and aggravated
      assault). Trauma victims reported greater perceived benefits and lower perceived
      risks associated with risky sexual behavior, illicit drug use, and heavy
      drinking, but not aggressive/illegal behavior than nonvictims. Victims also
      reported greater expected involvement in risky sex behavior, drug use, and heavy
      drinking. Regression analyses revealed that the relationship between victim
      status and expected involvement in risky behaviors was mediated by cognitions
      about risks and benefits of risky behavior, controlling for trauma-related
      symptoms. Implications of the findings for the understanding of repeat
      victimization are discussed.

PMID- 15245682
TI  - Policy makers' perspectives on the utility of a national study of child
      maltreatment.
AB  - Reliable national child maltreatment data are needed for developing and modifying
      policies aimed at preventing child maltreatment and helping child victims of
      maltreatment. Health Canada hosted a daylong forum in 2002 to solicit feedback
      from senior Government of Canada policy and program officials involved in child
      welfare programs and research in regard to the data collected in the Canadian
      Incidence Study of Reported Child Abuse and Neglect (CIS). This article reviews
      the discussions and debates regarding the utility of the CIS data for government
      policy makers and reflects on the implications for surveillance and knowledge in
      the area of child maltreatment. The key themes are definitions and measurement
      issues, the value of enhanced and additional data, and challenges to linking
      research and practice.

PMID- 15245683
TI  - Perceptions of child maltreatment by parents from the Indian subcontinent:
      challenging myths about culturally based abusive parenting practices.
AB  - Clinicians and researchers emphasize the importance of recognizing differential
      cross-cultural definitions of child maltreatment, cautioning awareness that some
      ethnic groups may use harsher methods to discipline their children. Using a mixed
      method research approach, based on questionnaire and focus group data, 29 parents
      of South Asian descent provided input on their attitudes toward child discipline,
      maltreatment, and neglect. Study findings suggest that South Asian parents do not
      differ significantly from other populations in their judgment of appropriate
      parenting approaches; that is, persistent and excessive use of physical
      discipline was considered to be inappropriate, behaviors of parents that may have
      negative emotional consequences for children were recognized as inappropriate,
      and lack of proper supervision of children was seen as a concern. Notably,
      though, participants voiced their reluctance to contact child protective services
      should they encounter families struggling with abuse. Implications for practice
      and directions for future research are suggested.

PMID- 15245684
TI  - The impact of type of out-of-court disclosure in a child sexual assault trial.
AB  - This study investigated the impact of type of out-of-court disclosure in a child
      sexual assault case involving a 6-year-old alleged victim. Community participants
      read a fictional criminal trial summary of a child sexual assault case in which
      the alleged victim's out-of-court disclosure of the assault was: (a) complete on
      two occasions or (b) incomplete at first, but later included the full account of
      the incident. The results showed that there were more guilty verdicts, higher
      ratings of the defendant's guilt, and greater belief of the alleged victim when
      there was full disclosure on two occasions compared to when there was a delay in
      full disclosure. These results are discussed in terms of the impact the nature of
      out-of-court disclosure can have when a child testifies in a sexual assault case.

PMID- 15245686
TI  - Forensic odontology: the roles and responsibilities of the dentist.
AB  - Dentistry has much to offer law enforcement in the detection and solution of
      crime or in civil proceedings. Forensic dental fieldwork requires an
      interdisciplinary knowledge of dental science. Most often the role of the
      forensic odontologist is to establish a person's identity. Teeth, with their
      physiologic variations, pathoses and effects of therapy, record information that
      remains throughout life and beyond. The teeth may also be used as weapons and,
      under certain circumstances, may leave information about the identity of the
      biter. Forensic odontology has an important role in the recognition of abuse
      among persons of all ages. Dental professionals have a major role to play in
      keeping accurate dental records and providing all necessary information so that
      legal authorities may recognize malpractice, negligence, fraud or abuse, and
      identify unknown humans.

PMID- 15245687
TI  - Incorporating retrievability in fixed implant-supported prostheses by transverse
      fixation in the ITI abutment system.
AB  - This article describes the use of the ITI implant system in rehabilitation of the
      maxillary anterior sextant of a 41-year-old patient. The Syn-Octa TS abutment
      system was used in this case, along with a customized transfer aid for intraoral
      positioning of these elements. This system offers the advantage of retrievability
      of the prosthesis in multiunit cases.

PMID- 15245688
TI  - Congenital maxillary double lip: review of the literature and report of a case.
AB  - A double lip is an anomaly that may be either congenital or acquired. It occurs
      most often in the upper lip, although both upper and lower lips are occasionally
      involved. Surgical intervention (simple excision) produces good functional and
      cosmetic results. In this report, we describe a case of congenital double upper
      lip, present a review of the literature and discuss the differential diagnosis.
      Double lip is of special interest in dentistry because the general practitioner
      is often the first professional to detect and establish the diagnosis of this
      uncommon condition.

PMID- 15245689
TI  - A closer look at diagnosis in clinical dental practice: part 4. Effectiveness of
      nonradiographic diagnostic procedures and devices in dental practice.
AB  - This article, the fourth in a series, examines nonradiographic procedures and
      devices such as standard clinical and visual examination, apex locators, vitality
      testers and colour shade guides in light of the tools described in the first 2
      articles in the series. A variety of nonradiographic indices and scales are used
      in detecting periodontal disease and monitoring and assessing its treatment. The
      reliability of these diagnostic procedures directly affects treatment success,
      decisions to initiate more aggressive clinical interventions, and the ability to
      make an informed prognosis about the course of the disease. However, in many
      instances, the dependability of the measurements remains to be established.

PMID- 15245690
TI  - Effectiveness and cost-effectiveness of imatinib for first-line treatment of
      chronic myeloid leukaemia in chronic phase: a systematic review and economic
      analysis.
AB  - OBJECTIVES: To evaluate the effectiveness of imatinib as first-line treatment for
      chronic myeloid leukaemia (CML) compared with interferon-alpha (IFN-alpha),
      hydroxyurea and bone marrow transplantation (BMT), and the cost-effectiveness of
      imatinib compared with IFN-alpha and hydroxyurea. DATA SOURCES: Electronic
      databases. REVIEW METHODS: Selected studies and full-text articles were screened
      and rigorously selected. Survival was the key outcome measure. Surrogate outcome
      measures included haematological (blood) response and cytogenetic (bone marrow)
      response (CR). As no published cost-effectiveness studies were found that
      compared imatinib and IFN-alpha, an independent Markov model was constructed and
      this was compared with models submitted to the National Institute for Clinical
      Excellence by the manufacturer of imatinib. RESULTS: Intention-to-treat analysis
      showed that imatinib was associated with complete CR at 12 months follow-up of
      68% compared with 20% for the IFN-alpha plus Ara-C group. The estimated
      proportion of people taking imatinib who had not progressed to accelerated or
      blast phases at 12 months was 98.5%, and 93.1% for IFN-alpha plus Ara-C. Overall
      survival was not statistically significantly different. Withdrawal due to side
      effects was 2% for imatinib and 5.6% for IFN-alpha plus Ara-C. Cross-over due to
      intolerance was 0.7% and 22.8% for imatinib and for IFN-alpha plus Ara-C,
      respectively. Quality of life was better in the imatinib group than the IFN-alpha
      group when assessed at 1, 3 and 6 months. Median survival across the four IFN
      alpha versus hydroxyurea studies was 66 and 56.2 months, respectively. Median
      complete CR was 6% for IFN-alpha and 0 for hydroxyurea. Median withdrawal due to
      side-effects was 24% and 4% for IFN-alpha and hydroxyurea, respectively. Four out
      of the five studies comparing BMT and IFN-alpha showed a long-term survival
      advantage for BMT over IFN-alpha, but a short-term disadvantage. In four of the
      five studies comparing BMT and IFN-alpha, median survival had not yet been
      reached in the BMT groups in 6--10 years. Median survival in the IFN-alpha arms
      ranged from 5.2 to 7 years. The BMT group gained a survival advantage over IFN
      alpha at 3--5.5 years. In the BMT group death due to transplant-related
      complications ranged from 36 to 45%. The incremental cost-effectiveness ratio
      (ICER) of imatinib compared with IFN-alpha from the independent model was
      GBP26,180 per quality-adjusted-life-years (QALY) gained and was relatively
      robust. Imatinib was less cost-effective than hydroxyurea with an ICER of
      GBP86,934. CONCLUSIONS: Imatinib appears to be more effective than current
      standard drug treatments in terms of cytogenetic response and progression-free
      survival, with fewer side-effects. However, there is uncertainty concerning
      longer term outcomes, the development of resistance to imatinib, the duration of
      response and the place of imatinib relative to BMT. New issues are continually
      arising, such as optimal management pathways and combination therapies.
      Recommendations for research include: long-term follow-up data from the first-
      and second-line imatinib trials; investigation into specific subgroups, e.g. high
      risk patients, the elderly, children or those eligible for BMT; long-term
      comparisons of imatinib with BMT performed in early stages of CML; the use of
      imatinib in combination with other therapies, and further detailed economic
      studies. Investigation of the impact of CML and imatinib on quality of life is
      also important.

PMID- 15245691
TI  - When to treat patients with chronic hepatitis C.

PMID- 15245692
TI  - Abnormal liver tests with unexplained cause in patients with hepatitis C virus
      infection.

PMID- 15245693
TI  - ERCP in hepatic hydatid disease.

PMID- 15245694
TI  - Pyogenic and amebic liver abscesses.
AB  - Pyogenic and amebic liver abscesses are the two most common hepatic abscesses.
      Amebic abscesses are more common in areas where Entamoeba histolytica is endemic,
      whereas pyogenic abscesses are more common in developed countries. Pyogenic
      abscess severity is dependent on the bacterial source and the underlying
      condition of the patient. Amebic liver abscess is more prevalent in individuals
      with suppressed cell-mediated immunity, men, and younger people. The right lobe
      of the liver is the most likely site of infection in both types of hepatic
      abscess. Patients usually present with a combination of fever, right-upper
      quadrant abdominal pain, and hepatomegaly. Jaundice is more common in the
      pyogenic abscess. The diagnosis is often delayed and is usually made through a
      combination of radiologic imaging and microbiologic, serologic, and percutaneous
      techniques. Treatment involves antibiotics along with percutaneous drainage or
      surgery.

PMID- 15245695
TI  - Infectious complications of pancreatitis: diagnosis and management.
AB  - Infected pancreatic necrosis is the leading cause of death in patients with
      severe acute pancreatitis. Early prophylactic antibiotic treatment is effective
      in preventing conversion of sterile necrosis to pancreatic infection, but its
      effect on mortality remains unproven. Fungal infections may predict a worse
      outcome, but no evidence supports the use of antifungal prophylaxis. Because
      infection of pancreatic necrosis by enteric bacteria can develop despite
      prophylaxis, a high index of suspicion should allow early detection followed by
      aggressive management.

PMID- 15245696
TI  - Helminthic infections of the liver.
AB  - Human helminthic infestation is exceedingly common on a global scale, with as
      many as 1.5 to 2 billion people affected worldwide. Helminths (parasitic worms)
      that infect the liver and hepatobiliary system include nematodes (roundworms),
      cestodes (tapeworms), and trematodes (flatworms or flukes). The majority of
      morbidity and mortality from these infestations is caused by the host immune
      response to the larvae or adult worm. Helminthic disease manifestations vary from
      the extremes of asymptomatic carriage to cirrhosis and decompensated liver
      disease. Current basic science and clinical research focus on improvements in
      medical therapy, mass screening and chemoprophylaxis, and the development of
      preventative vaccine strategies.

PMID- 15245697
TI  - Update on Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 infection is one of the more intriguing emerging
      infectious diseases of the industrialized world. The clinical importance of this
      organism first came to light in the 1980s and has been associated with
      significant morbidity and mortality in the United States. The infection is more
      common in industrialized countries than developing ones and is most closely
      associated with asymptomatic colonization of cattle. Fecal oral transmission is
      the rule, with the inoculum needed for infection much smaller than that required
      for E. coli-related travelers' diarrhea. The organism can survive for months in
      the environment, and cross contamination is common. Watery diarrhea that
      progresses to bloody diarrhea without prominent fever is the classic
      presentation. The classic biopsy finding is similar to that of ischemic colitis,
      with acute inflammation and hemorrhage involving the superficial mucosa with
      preservation of the deeper crypts. E. coli O157:H7 has powerful Shigella-like
      toxins that are encoded by bacteriophages and can trigger thrombotic
      complications such as the hemolytic uremic syndrome or thrombotic
      thrombocytopenic purpura. The very young and the elderly are most at risk for
      serious disease and complications. Treatment with antibiotics has been reported
      to increase the risk for complications, but the evidence supporting this
      conclusion is unconvincing, with many variables affecting outcome in any one
      patient.

PMID- 15245698
TI  - Low-dose growth hormone in home parenteral nutrition for short bowel patients.

PMID- 15245699
TI  - Effect of enteral and parenteral nutrition on markers of severe acute
      pancreatitis.

PMID- 15245700
TI  - The use of oral rehydration solutions in children and adults.
AB  - The observation that the intestinal Na(+)-glucose cotransporter remains intact in
      most diarrheal illnesses led to development of the life-saving, low-cost
      technology of oral rehydration salt (ORS) solutions. The primary therapeutic role
      of ORS solutions is in prevention and treatment of dehydration during management
      of acute gastroenteritis. Successful oral rehydration therapy involves early use
      of ORS with maintenance or timely resumption of regular feeding. Since the
      inception of the oral rehydration approach more than three decades ago, the
      widespread use of ORS solutions has revolutionized the management and outcomes of
      acute gastroenteritis in children and adults. The efficacy of the World Health
      Organization ORS solution and of commercial ORS formulations has been enhanced by
      reducing osmolarity. Newer formulations of ORS are under active investigation,
      with promise of added benefits, including promotion of intestinal healing. This
      article reviews fluid and electrolyte transport in the gastrointestinal tract,
      the pathophysiologic mechanisms of acute diarrhea, and the basis and formulation
      of current and newer ORS solutions. Guidelines for efficacious use of ORS in the
      management of acute gastroenteritis and short gut syndrome are also provided.

PMID- 15245701
TI  - Ethics and gastrointestinal artificial feeding.
AB  - Medical ethics is the study of human values as they relate to the practice of
      medicine. Ethics intersects with gastroenterology primarily involving issues of
      gastric and intestinal artificial feeding at the end of life. Language imparts
      meaning. Gastric artificial feeding is not the same as eating. Recent data
      suggest that gastric artificial feeding does not prolong life in patients with
      dementia and dysphagia. Given the lack of documented benefit of gastrointestinal
      feeding in these patients, the literature has focused on selection of appropriate
      patients for this medical intervention. Ethical care involves compassion,
      communication, consultation, and collaboration in dealing with emotionally
      difficult circumstances.

PMID- 15245702
TI  - Nutritional support in acute pancreatitis.
AB  - Acute pancreatitis is one of the most catabolic of critical illnesses, and its
      clinical course is often prolonged. Consequently, the need for interventional
      nutritional support is great. Because of fears that feeding might exacerbate the
      tryptic autodigestion and disease process, total parenteral nutrition was used
      exclusively until recent years, when it was recognized that the complications of
      hyperglycemia and sepsis outweighed nutritional benefits. In clinical practice,
      enteral feeding has proven superior because it avoids these complications and
      maintains gut function, but enteral feeding needs to be given in a form that
      minimizes pancreatic stimulation. This review discusses the advances in our
      understanding of the pathophysiology of the disease, the results of recent
      clinical trials of nutritional support, and the challenges that remain in
      optimizing nutritional management.

PMID- 15245703
TI  - Metabolic and catheter complications of parenteral nutrition.
AB  - Since its introduction in the 1960s, total parenteral nutrition (TPN) has played
      a vital role in improving clinical outcomes for patients with acute and chronic
      illnesses. The evolution of TPN solutions and vascular access techniques,
      combined with an increased awareness and better understanding of the physiology
      of TPN, have improved the safety of this therapy. Nevertheless, complications are
      not uncommon and can be life threatening. This article provides an updated review
      on the metabolic and catheter complications associated with TPN.

PMID- 15245704
TI  - Metabolic bone disease and parenteral nutrition.
AB  - Metabolic bone disease (MBD) is abnormal bone metabolism and includes the common
      disorders of osteoporosis and osteomalacia, which can develop in patients
      receiving long-term parenteral nutrition (PN). Patients who require long-term PN
      have significant gastrointestinal failure and malabsorption, which is generally
      caused by severe inflammatory bowel disease, intestinal ischemia, or malignancy.
      The exact cause of MBD in long-term PN patients is unknown, but its origin is
      thought to be multifactorial, with factors including underlying disease, effect
      of medications used to treat this disease (eg, corticosteroids), and various
      components of the PN solution. Caring for patients on long-term PN requires
      routine assessment and monitoring for MBD. Appropriate adjustments of the PN
      solution can help reduce the risk for developing PN-associated MBD and in some
      instances improve bone mineral density. Recent developments in pharmacologic
      treatment for osteoporosis show promise for patients with MBD receiving PN.

PMID- 15245705
TI  - Editorial. Systematic review--what is it and how should it be used?

PMID- 15245706
TI  - Unravelling the complexity of muscle impairment in chronic neck pain.
AB  - Exercise interventions are deemed essential for the effective management of
      patients with neck pain. However, there has been a lack of consensus on optimal
      exercise prescription, which has resulted from a paucity of studies to quantify
      the precise nature of muscle impairment, in people with neck pain. This
      masterclass will present recent research from our laboratory, which has utilized
      surface electromyography to investigate cervical flexor muscle impairment in
      patients with chronic neck pain. This research has identified deficits in the
      motor control of the deep and superficial cervical flexor muscles in people with
      chronic neck pain, characterized by a delay in onset of neck muscle contraction
      associated with movement of the upper limb. In addition, people with neck pain
      demonstrate an altered pattern of muscle activation, which is characterized by
      reduced deep cervical flexor muscle activity during a low load cognitive task and
      increased activity of the superficial cervical flexor muscles during both
      cognitive tasks and functional activities. The results have demonstrated the
      complex, multifaceted nature of cervical muscle impairment, which exists in
      people with a history of neck pain. In turn, this has considerable implications
      for the rehabilitation of muscle function in people with neck pain disorders.

PMID- 15245707
TI  - The centralization phenomenon of spinal symptoms--a systematic review.
AB  - The centralization phenomenon was first described 20 years ago. It refers to the
      abolition of distal pain emanating from the spine in response to therapeutic
      exercises. Since then a number of papers on the subject have been published. A
      review of current knowledge is appropriate. Selection criteria were established
      prior to a computer-aided search for published papers. Two reviewers
      independently extracted data and checked quality; a third reviewer resolved any
      disagreements. A narrative review was conducted based on the findings. The review
      primarily considered prevalence, reliability of assessment, and prognostic
      significance. These have been most commonly reported, and are important to
      establish the clinical worth of this symptom response. Fourteen studies were
      identified. Quality of studies varied; prognostic studies were given a mean score
      of 3.3 out of 6 by using established quality criteria. The prevalence rate of
      pure or partial centralization was 70% in 731 sub-acute back patients, and 52% in
      325 chronic back patients. It is a symptom response that can be reliably assessed
      during examination (kappa values 0.51-1.0). Centralization was consistently
      associated with a range of good outcomes, and failure to centralize with a poor
      outcome. Centralization appears to identify a substantial sub-group of spinal
      patients; it is a clinical phenomenon that can be reliably detected, and is
      associated with a good prognosis. Centralization should be monitored in the
      examination of spinal patients.

PMID- 15245708
TI  - Clinicians' perceptions of minor cervical instability.
AB  - Appropriate musculoskeletal physiotherapy management of spinal conditions
      requires recognition of clinical patterns in order to make a provisional
      diagnosis. This study aimed to assist the recognition of minor cervical
      instability (MCI) by surveying clinicians experienced in the management of neck
      conditions. A total of 153 Australian physiotherapists with postgraduate
      qualifications in manipulative physiotherapy and experience in the management of
      neck conditions completed a questionnaire that required them to indicate the
      importance of 15 clinical findings in the diagnosis of MCI. The responses were
      examined descriptively then subjected to factor analysis to identify possible
      groupings of findings. Clinical findings considered by greater than 50% of
      respondents to be either very important or vitally important in the diagnosis of
      MCI were: a history of major trauma; reports of the neck catching or locking or
      giving way; poor muscular control; signs of hypermobility on X-ray; excessively
      free end-feel on passive motion testing and unpredictability of symptoms. The
      factor analysis resulted in four distinct factors, each clinically interpretable.
      Therapists treating patients with neck conditions should at least consider the
      possibility of MCI when presented with any of the six findings reported above or
      with any of the groupings of findings identified by the factor analysis.

PMID- 15245709
TI  - How common are side effects of spinal manipulation and can these side effects be
      predicted?
AB  - Little scientific support is available concerning usual and unusual reactions
      after spinal manipulation although such reactions are very common in clinical
      practice. Fifty-nine manipulative therapists were requested to enroll 15
      consecutive patients attending for their first visit to receive spinal
      manipulation. These patients were asked to complete a questionnaire after this
      first visit that asked for possible risk factors for spinal manipulation and
      asked about any side effects after the manipulation. The participating
      practitioners were asked to note medical diagnosis, manipulated spinal region,
      number of treated areas and type of additional treatment. Four hundred and sixty
      five valuable responses were analysed. Two hundred and eighty three patients
      (60.9%) reported at least one post-manipulative reaction. The most common were
      headache (19.8%), stiffness (19.5%), local discomfort (15.2%), radiating
      discomfort (12.1%) and fatigue (12.1%). Most of these reactions began within 4 h
      and generally disappeared within the next 24 h. Women were more likely to report
      adverse effects than men (P < 0.001). Multivariate analysis showed that upper
      cervical manipulation (OR: 3.20; 95%CI: 1.89-7.77), use of medication (OR: 2.20;
      95%CI: 1.31-3.69), gender (OR: 1.66; 95%CI: 1.01-2.75) and age (OR: 1.02; 95%CI:
      1.00-1.05) were independent predictors of headache after spinal manipulation. The
      results of this study indicate that reactions to spinal manipulation may be
      relatively common but are benign in nature and of short duration. Although it is
      difficult to label side effects as a risk, it is important to differentiate those
      patients who are susceptible to side effects in order to inform them correctly.

PMID- 15245710
TI  - Impaired trunk muscle function in sub-acute neck pain: etiologic in the
      subsequent development of low back pain?
AB  - Low back pain (LBP) and neck pain are associated with dysfunction of the trunk
      and neck muscles, respectively, and may involve common or similar mechanisms. In
      both cases, dysfunction may compromise spinal control. Anecdotally, neck pain
      patients commonly develop LBP. This study investigated the possibility that trunk
      muscle function is compromised in neck pain patients and that compromised trunk
      muscle function is associated with increased risk of LBP. Fifty-four neck pain
      patients and 52 controls were assessed on an abdominal drawing-in task (ADIT) and
      on self-report tests. Performance on the ADIT was able to detect neck pain
      patients with 85% sensitivity and 73% specificity. Catastrophizing and McGill
      pain questionnaire (affective) scores were higher in patients with an abnormal
      task response than in patients with an uncertain or normal response, although the
      self-report data did not predict task performance. Fifty subjects from each group
      were contactable by telephone at 2 years. They were asked whether they had
      experienced persistent or recurrent LBP since the assessment. Subjects (patients
      and controls) who obtained an abnormal response on the ADIT were 3 to 6 times
      more likely to develop persistent or recurrent LBP than those who obtained an
      uncertain or normal response. ADIT performance was the main predictor of
      development of LBP in patients. The results suggest that reduced voluntary trunk
      muscle control in neck pain patients is associated with an increased risk of
      developing LBP.

PMID- 15245711
TI  - A survey on the importance of lumbar coupling biomechanics in physiotherapy
      practice.
AB  - Knowledge of lumbar coupling biomechanics is foundational in many manual therapy
      disciplines. 3-D studies of lumbar coupling indicate that coupling direction may
      not be predictable. The purpose of this study was to investigate
      physiotherapists' perception of importance of lumbar coupling for validation of
      manual therapy, necessity in treatment, and perceived direction of lumbar
      coupling biomechanics. A sample of 369 physiotherapists within the United States
      volunteered to participate in this study. An ologit regression analysis
      investigated factors associated with perception of lumbar coupling. A Fleiss
      Kappa determined the agreement of coupling direction among physiotherapists. The
      majority of physiotherapists indicated that lumbar coupling biomechanics were
      important or very important, frequently used during treatment, and necessary for
      validation of manual therapy. The ologit regressions identified that the
      importance placed upon lumbar coupling biomechanics is highly related toward
      therapists' pre-concept of coupling. Kappa values for the five spinal segments
      were negative indicating worse than chance agreement: L1-2 = -0.10; L2-3 = -0.11;
      L3-4 = -0.09; L4-5 = -0.10; and L5-S1 = -0.09. The poor Kappa values, strong pre
      conceptual perceptions of coupling necessity, and the importance placed upon
      lumbar coupling for treatment could lead to disparities among physiotherapists in
      lumbar manual therapy assessment and treatment.

PMID- 15245713
TI  - Education in internal medicine.

PMID- 15245712
TI  - A case of selective paresis of the deep stabilization system due to borreliosis.

PMID- 15245714
TI  - Positron emission tomography: a coming of age?

PMID- 15245715
TI  - The antiphospholipid (Hughes') syndrome: changing the face of neurology.
AB  - Hughes' syndrome (the antiphospholipid syndrome (APS)) presents with recurrent
      thrombosis, recurrent miscarriage and neurological disease. The major pathogenic
      mechanism of the syndrome is vascular obstruction (both venous and arterial) due
      to hypercoagulability. Neurological manifestations are prominent and are often
      the dominant feature. Headache, migraine and cognitive dysfunction are common
      while other manifestations such as dementia, epilepsy, chorea, multiple sclerosis
      (MS), psychiatric disease, transverse myelitis, ocular syndromes, sensorineural
      hearing loss and movement disorders are also associated with the syndrome.
      Anticoagulation therapy (either aspirin or oral anticoagulants) can lead to
      significant improvement.

PMID- 15245716
TI  - Contribution of (18)fluoro-deoxyglucose positron emission tomography to the work
      up of patients with fever of unknown origin.
AB  - Background: Recent studies have suggested that (18)fluoro-deoxyglucose (FDG)
      positron emission tomography (PET) may be useful in the work-up of patients with
      fever of unknown origin (FUO), but its exact diagnostic yield has not been
      established. Methods: From January 1999 through December 2001, 74 (67%) of 110
      prospectively collected patients who fulfilled the revised criteria of classic
      FUO underwent a FDG-PET scan. The diagnostic yield of this technique was assessed
      after diagnostic work-up and follow-up. Abnormal FDG-PET scans that pointed to
      the final diagnosis were categorized as helpful; all other scans were considered
      noncontributory. Results: A final diagnosis was established in 39 (53%) of the 74
      patients who underwent FDG-PET. Fifty-three (72%) of the 74 FDG-PET scans were
      abnormal; 19 scans (36% of the abnormal scans or 26% of the total number of
      scans) were helpful. In the 39 patients with a final diagnosis, 49% of the scans
      were helpful. A diagnosis was established in 31 (58%) of the 53 patients with an
      abnormal scan and in 8 (38%) of the 21 patients with a normal scan (P=0.2).
      Baseline clinical variables (age and sex, as well as periodicity, duration, and
      height of the fever) and inflammatory parameters (erythrocyte sedimentation rate,
      C-reactive protein, and hemoglobin) did not predict the usefulness of FDG-PET.
      Conclusions: FDG-PET contributed positively to the diagnosis in a quarter of our
      patients with classical FUO. This number is lower than that found in previous
      studies. Yet, against the background of the wide array of heterogeneous disorders
      that make up the FUO spectrum and the low number of final diagnoses established
      (in only 53% of cases), the diagnostic yield of FDG-PET is encouraging.
      Therefore, the use of FDG-PET should be considered whenever a baseline work-up
      fails to reveal the cause of a prolonged, febrile illness.

PMID- 15245717
TI  - Accurate topographical diagnosis of urinary tract infection in male patients with
      (111)indium-labelled leukocyte scintigraphy.
AB  - Background: Although the clinical diagnosis of urinary tract infection (UTI) is
      straightforward, the precise localization of the urogenital organ affected by the
      infection is often difficult to establish. Methods: To evaluate this, we
      prospectively studied 20 males with a clinical diagnosis of acute pyelonephritis
      (APN), acute prostatitis (AP) and febrile UTI (FUTI), as well as seven control
      females with APN. (111)Indium-labelled leukocyte scintigraphy (ILS) was performed
      during the febrile episode and repeated when patients were free of symptoms.
      Results: ILS showed an abnormal uptake in a urinary organ in every case. All
      patients with AP showed uptake in the pelvic area. Four male patients presented
      AP, one of them had uptake in the lumbar area, one in the lumbar and pelvic area,
      and two in the area of the prostate only. Six out of seven patients with FUTI
      presented uptake in the pelvic area. All female patients showed kidney uptake.
      After the clinical resolution of the UTI, no residual uptake was found in any
      case except for one. Conclusions: These results suggest that ILS is very useful
      in localizing the affected organ in febrile UTI. Most male patients with a
      febrile UTI presented a prostatic involvement, suggesting that many cases of APN
      or FUTI in males may actually be cases of AP not recognized by standard clinical
      evaluation.

PMID- 15245718
TI  - Thrombotic risk in patients submitted to splenectomy for systemic lupus
      erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia.
AB  - Background: Splenectomy has been performed to treat refractory autoimmune
      thrombocytopenia. However, some reports have suggested that an increased risk of
      thrombosis could be present in splenectomized patients. This study aims to
      evaluate the possibility of an increased risk of thrombosis after splenectomy in
      patients with systemic lupus and antiphospholipid syndrome. Methods: Thrombotic
      related events in patients with systemic lupus erythematosus (SLE) and/or primary
      antiphospholipid syndrome (PAPS), before and after splenectomy for severe
      thrombocytopenia, were compared. Clinical data, laboratory investigations, and
      anticoagulation or antiaggregation treatment data were collected from the notes
      of outpatients attending three European centers. Results: Twenty patients who had
      had a splenectomy were identified: eight with SLE, five with PAPS, and seven with
      SLE and APS. The mean time between diagnosis and splenectomy was 3.1 years and
      mean follow-up was 6.5 years. There were no differences in anticardiolipin
      antibody titers, lupus anticoagulant, anti-DNA or anti-nuclear antibodies before
      and after surgery. The incidence of venous events before and after splenectomy
      was not significantly different. There was a trend towards an increase in the
      total number of arterial events post-splenectomy. In aCL-positive patients, and
      in the pre-splenectomy period, the total number of miscarriages was higher
      (p=0.017), as was the number of patients who had had a miscarriage (p=0.025).
      Conclusions: The total risk of thrombosis in patients with PAPS and SLE was not
      increased after splenectomy, but there was a trend towards an increase in the
      number of arterial events. Splenectomy induced long-term remission of
      thrombocytopenia (partial or complete) in all patients.

PMID- 15245719
TI  - Clinical and ethnic characteristics of stroke in an Israeli population: a study
      in a community hospital population.
AB  - Background: Stroke mainly affects the older population, although it has also been
      reported in younger patients. In this study, we focused on patients 65 years of
      age or younger with stroke. Methods: The files of three patient populations were
      studied: 93 patients aged 65 years or younger with stroke (group A), 93 patients
      older than 65 with stroke (group B), and 604 patients without stroke representing
      the general population of patients admitted to our service during January 2000
      (group C). We reviewed the patient files and compared patient characteristics,
      epidemiological features, clinical picture,imaging findings, and coagulation
      tests. Results: Overall, 318 patients were studied. The mean age of group A was
      55 years compared to 77 years in group B and 71 years in group C. In both stroke
      groups (A and B), the male: female ratio was 2:1, in contrast with a balanced
      ratio in group C. Most of the patients in group A (63%) were of Sephardic origin
      compared to 39% in group B (P=0.002) and 30% in group C. The clinical picture in
      both stroke groups (A and B) was similar. The risk factor smoking was reported by
      45% in group A and by only 29% in group B (P=0.034). Hypertension, diabetes
      mellitus, and hyperlipidemia were evenly prevalent in both stroke groups. The
      coagulation system was studied in the "young" patients (group A):
      hyperhomocysteinemia was found in 37%, high titers of anticardiolipin antibodies
      in 35%, low levels of antithrombin III in 13%, protein C deficiency in 5%, and
      activated protein C resistance (APCR) in 4%. Overall, 49% of the patients from
      group A were found to have coagulation abnormalities. Conclusions: We found in
      our study that the younger patient with stroke tends to be a Sephardic male with
      the classical risk factors as well as a history of smoking and coagulopathy.
      These findings suggest strict medical supervision and primary prophylaxis. This
      work also lays the basis for a prospective, interventional trial with younger
      patients.

PMID- 15245720
TI  - Effect of weight reduction on serum ghrelin and TNFalpha concentrations in obese
      women.
AB  - Background: Ghrelin causes weight gain by increasing food intake in rodents.
      Tumor necrosis factor alpha (TNFalpha) is produced by adipose tissue, modulates
      its metabolism and stimulates catabolic processes. The aim of our study was to
      evaluate whether weight loss treatment modulates serum concentrations of TNFalpha
      and ghrelin in obese women. Methods: The study groups included 46 women: 35 obese
      patients and 11 controls. Serum concentrations of ghrelin and TNFalpha were
      measured by ELISA before and after a 3-month weight reduction treatment that
      consisted of a 1000 kcal/day diet and physical exercises. Body composition was
      determined by impedance analysis using Bodystat. Results: There were no
      differences in plasma ghrelin concentrations between obese patients and controls.
      TNFalpha serum levels were higher in obese patients than in controls (p=0.000).
      The mean weight loss over the 3-month treatment period was 8.7+/-4.5 kg.
      Following weight loss, serum ghrelin concentration increased significantly
      (66.3+/-13.7 vs. 73.7+/-14.8 pg/ml; p=0.002) and TNFalpha concentrations
      decreased significantly (6.9+/-2.6 vs. 5.2+/-1.5 pg/ml; p=0.002). Ghrelin did not
      show a correlation with weight or percentage of body fat. There was a positive
      correlation between the increase in ghrelin and the decrease in body fat
      percentage during weight loss (p=0.002). Conclusion: The increase in serum
      ghrelin and the decrease in serum TNFalpha, as observed after weight reduction
      treatment in obese subjects, may constitute a counter-regulatory mechanism
      preventing further weight loss.

PMID- 15245721
TI  - The predictive value of white blood cell count on the success of primary
      percutaneous intervention of the left anterior descending artery in patients
      admitted with acute anterior wall myocardial infarction.
AB  - Background: Epidemiological studies have shown correlations between the white
      blood cell (WBC) count and the risk of acute myocardial infarction (AMI) and
      stroke. The risk of AMI is four times as great in patients with WBC counts in the
      high-normal range (>9000/microl) as it is in those in the low-normal range
      (<6000/microl). A high WBC count also predicts a greater risk of re-infarction
      and in-hospital death. Data are still missing about the role of WBC count in the
      success rate of primary angioplasty. Methods: A total of 125 consecutive patients
      aged 40-65 years (mean age 54+/-8 years) had a primary percutaneous coronary
      intervention (PCI) as their first-line therapy for AMI. We evaluated
      interrelationships between WBC count, hemoglobin (Hg), platelets (PLT), heart
      rate (HR), left ventricular systolic (LVS) pressure, left ventricular diastolic
      (LVD) pressure, and the success rate of primary angioplasty to the occluded left
      anterior descending artery (LAD) in patients with AMI. Results: Of the 125
      patients (30 females and 95 males), 72 underwent primary PCI to the LAD and 31
      patients were referred for an emergency coronary artery bypass graft surgery
      (CABG). One patient died. Twenty-one patients had non-occluded arteries, most of
      them with a fresh thrombus and after spontaneous reperfusion. Multiple logistic
      dregression analysis demonstrated that low ejection fraction (p=0.01) and high
      WBC counts (p=0.04) were correlated with failure of angioplasty and referral for
      an emergency CABG. WBC counts were positively correlated with heart rate
      (p=0.005), platelet count (p=0.0006), and Hg level (p=0.001). Conclusions: These
      data suggest that measuring WBC count on admission to the catheterization
      laboratory for primary angioplasty provides clinically important prognostic
      information.

PMID- 15245722
TI  - Usefulness of FDG-PET in detecting an ADH-secreting tumor: a case report.
AB  - We report a case of a 41-year-old woman who was diagnosed as having the syndrome
      of inappropriate secretion of ADH (SIADH). There was no evidence of any disorders
      of the central nervous system, lung diseases, or drugs causing SIADH. Positron
      emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) was performed and
      indicated a tumor of the uterine cervix. After resection of the tumor, both serum
      sodium level and serum osmolarity were normalized concomitantly with a decrease
      in serum ADH level. This is the first case report suggesting the usefulness of a
      FDG-PET scan to detect an occult cancer responsible for SIADH. It seems plausible
      that FDG-PET may be helpful in the diagnosis of other ectopic hormone-producing
      tumors such as ectopic ACTH-producing tumors that cause Cushing's syndrome.

PMID- 15245723
TI  - Nodular fasciitis: an unexpected finding on computed tomography and positron
      emission tomography.
AB  - Nodular fasciitis is an uncommon lesion that is also designated as a
      pseudosarcomatous, self-limiting reactive process. We describe a 40-year-old
      woman with a nodular fasciitis that was detected by computed tomography (CT),
      positron emission tomography (PET) with 18F-fluorodeoxyglucose (18-FDG), and
      histology while she was being examined for upper abdominal pain.

PMID- 15245724
TI  - Positron emission tomography as an aid in the diagnosis and follow-up of Riedel's
      thyroiditis.
AB  - We describe the usage of positron emission tomography (PET) as an aid in the
      initial diagnosis and follow-up of Riedel's thyroiditis. A 41-year-old patient
      was admitted for an enlarged and tender thyroid gland in association with severe
      systemic symptoms of inflammation. Imaging with fluorine-18 fluorodeoxyglucose
      (FDG) and PET demonstrated an intensive uptake of FDG in both lobes of the
      thyroid gland as an indication of severe inflammation. The diagnosis of Riedel's
      thyroiditis was confirmed by the histological findings of biopsy specimens taken
      during a palliative thyroid resection. The inflammatory symptoms and local pain
      dramatically disappeared after commencement of high-dose corticosteroid therapy.
      A follow-up PET scan after 2 weeks of corticosteroid treatment showed a 60%
      decrease in the uptake of FDG in the thyroid. This indicates that FDG metabolic
      activity can also be used to assess a patient's response to therapy in Riedel's
      thyroiditis.

PMID- 15245725
TI  - Intravascular malignant lymphomatosis diagnosed on a muscular biopsy: a case
      report.
AB  - Intravascular malignant lymphomatosis (IML) is characterized by proliferation of
      malignant lymphoid B cells within the lumens of small vessels. Common symptoms
      include general weakness and central neurological and cutaneous signs. Only
      histopathological analysis can confirm the diagnosis. We report on a 69-year-old
      man hospitalized for general weakness, inflammatory syndrome, and hemophagocytic
      syndrome (HS). Our observation shows that histopathological signs may be observed
      on a muscular biopsy without clinical or biological signs of muscular
      involvement.

PMID- 15245726
TI  - Management of massive lower gastrointestinal bleeding: should there be surgical
      intervention without initial endoscopy and radiological evidence of the source of
      bleeding?
AB  - We report two case histories of patients with massive rectal blood loss.
      Endoscopic and radiological investigations could not identify the source of
      bleeding at admission. Initially, both patients recovered without surgical
      intervention, receiving a large number of blood transfusions only. Extensive
      subsequent radiological analysis showed that the bleeding was due to a
      pathological part of the proximal jejunum in one case and of the colon
      transversum in the other. Although immediate surgical intervention was not needed
      at presentation, both patients underwent resection of a part of the bowel some
      time thereafter. Surgery was performed after hemodynamic stabilization in the
      first case. However, in the second case, emergency surgical intervention was
      needed due to persistent bleeding 4 days after admission. Both patients are still
      doing well half a year after this massive gastrointestinal (GI) hemorrhage. Aside
      from a small area of chronic inflammation and fibrosis of the jejunum in one
      patient, histopathological evaluation of the surgical resection specimens
      revealed no specific cause for these massive gastrointestinal bleedings. We
      discuss the general approach of gastrointestinal hemorrhage and the several
      (dis)advantages of the various imaging techniques and the order in which they
      should be used.

PMID- 15245727
TI  - Sarcoidosis presenting with isolated right paratracheal mass on chest X-ray.

PMID- 15245728
TI  - Hypercalcemia due to ectopic PTH?

PMID- 15245729
TI  - A de novo model of rational pharmacotherapy training: the interns' perspective.
AB  - Background: Poor prescribing habits can lead to ineffective and unsafe treatment,
      exacerbation or prolongation of illness, distress and harm to the patient, and
      higher costs. Rational pharmacotherapy training is very important for reducing
      poor prescribing practices, especially in developing countries. The aim of this
      study was to evaluate interns' satisfaction with a rational pharmacotherapy
      training program at the Department of Internal Medicine of our university.
      Methods: Rational pharmacotherapy training, designed by the WHO Action Program on
      Essential Drug Advice, was the subject of the study. Interactive learning
      methods, such as small group discussions and role-playing, were used as training
      methods. All of the interns in the class of 2003 participated in the training
      during their internal medicine internship period. Perceptions of the interns were
      collected via a 15-item feedback questionnaire. A 5-point Likert scale was used
      for scoring, and mean values were calculated for every item. Results: Mean values
      of all items were higher than 4, except for the control item. Interns'
      satisfaction with the training differed significantly in the third week, which
      focused on the physician-patient relationship. Interns suggested that this
      training should be performed in other classes and apprenticeship periods.
      Conclusions: This was the first training program in Turkey. Rational
      pharmacotherapy training should be integrated into the medical curriculum and
      performed using a multidisciplinary approach.

PMID- 15245730
TI  - Dynamic imaging of the immune system.

PMID- 15245731
TI  - Elucidating the functional anatomy of secondary lymphoid organs.
AB  - Functional anatomy offers an attempt to exploit anatomical information as a
      platform from which to decipher mechanistic details of complex or multistep
      immunological processes. Immune function depends on structural organization,
      therefore this approach contributes to a comprehensive understanding of the
      immune system. Major advances in functional anatomy require progress in both
      experimental techniques and analytical equipment - largely synonymous to
      refinement of the anatomist's favorite tool, the microscope. Here, we describe
      how currently available techniques co-operate to gain new insights into the
      biology of secondary lymphoid organs.

PMID- 15245732
TI  - Real-time imaging of T-cell development.
AB  - The cellular and molecular dynamics underlying intrathymic T-cell development are
      still poorly understood. Dynamic imaging techniques offer new opportunities for
      dissecting the complex journey of developing T cells in the thymus. In
      particular, two-photon laser scanning microscopy has recently demonstrated great
      promise in tracking lymphocyte behavior in tissue environments. Resolving
      thymocyte behavior at the single-cell level should help to clarify the mode of
      trafficking in the thymus and identify the spatio-temporal aspects of thymic
      selection events.

PMID- 15245733
TI  - In vivo imaging of leukocyte trafficking in blood vessels and tissues.
AB  - Selective recruitment of blood-borne leukocytes to tissues and their proper
      positioning within them is crucial for the many integrated functions of the
      immune system. Intravital microscopy (IVM) techniques have been employed for more
      than a century to study these events at the single-cell level in living animals.
      Conventional video-based IVM allows the visualization of extremely rapid adhesion
      events at the interface between blood and tissue. Multiphoton IVM is a relatively
      new tool for imaging the slower dynamics of cell migration and cell-cell
      interactions in the extravascular space in three dimensions. Fueled by the
      burgeoning development of sophisticated fluorescent markers and increasingly
      powerful imaging tools, we are currently witnessing the emergence of a new field
      in immuno-imaging, in which leukocyte function and cell-cell communication is
      explored in a truly physiological context.

PMID- 15245735
TI  - Real-time visualization of the cytoskeleton and effector functions in T cells.
AB  - Advances in imaging technology have been essential to our understanding of T-cell
      activation and effector functions. Much of the progress stems from the use of
      fluorescent fusion proteins combined with high resolution imaging techniques,
      including confocal and multiphoton microscopy. However, these techniques have
      limitations, and other modes of imaging, including new developments on the
      horizon, might add promising new tools for the visualization of cytoskeleton
      dependent processes in living cells.

PMID- 15245734
TI  - Using live FRET imaging to reveal early protein-protein interactions during T
      cell activation.
AB  - The emerging challenge for proteomics in general and lymphocyte biology in
      particular is to understand protein-protein interactions in the dynamic context
      of the living cell. Particularly interesting are the molecular dynamics of the T
      cell receptor-CD3 complex and other immunoreceptors in immune synapses.
      Fluorescence (or Forster) resonance energy transfer (FRET) is one of the few
      techniques that are capable of giving dynamic information about the nanometer
      range proximity between molecules, as opposed to simply the subcellular co
      localization that is provided by fluorescence microscopy. Spectral changes in
      fluorescence intensity and down modulation of donor lifetime are the basis for
      rapidly developing approaches to real-time FRET imaging. With two-photon
      excitation, FRET can now be extended to in vivo imaging.

PMID- 15245736
TI  - Host-pathogen interactions.

PMID- 15245737
TI  - Immunological memory to viral infection.
AB  - Immunological memory is defined by the ability of a host to remember a past
      encounter with a specific pathogen and to respond to it in an effective manner
      upon re-exposure. How long immunological memory can be maintained in the absence
      of re-infection continues to be a subject of great controversy. Recent studies on
      immunity following smallpox vaccination demonstrate that T-cell memory declines
      steadily with a half-life of 8-15 years, whereas antiviral antibody responses are
      maintained for up to 75 years without appreciable decline. By combining recent
      advances in quantitative immunology with historical accounts of protection
      against smallpox dating back to the time of Edward Jenner, we are gaining a
      better understanding of the duration and magnitude of immunological memory and
      how it relates to protective immunity.

PMID- 15245738
TI  - CD8+ T-cell memory: only the good ones last.
AB  - Generating long-lasting, protective CD8(+) T-cell memory via vaccination is
      critical for combating infectious diseases. Advances in the past year have
      provided many new insights into how memory CD8(+) T cells are generated. It is
      now recognized that CD8(+) T cells differentiate from 'effector memory' cells
      into 'central memory' cells, which are stably maintained and confer superior
      protective immunity. Furthermore, CD4(+) T-cell help plays an important role in
      guiding the differentiation of CD8(+) T cells into long-lasting, functional
      memory. These findings have important implications for developing vaccine
      strategies that induce high-quality CD8(+) T-cell memory, not just high quantity.

PMID- 15245739
TI  - Immune evasion by gamma-herpesviruses.
AB  - Persistent viruses, such as herpesviruses, transmit infection by evading
      cytotoxic T cells during lytic replication. The gamma-herpesviruses additionally
      evade T cells during the proliferation of latently infected lymphocytes to
      establish a persistent viral reservoir. Lytic gene expression in sites of
      lymphoproliferation appears to make a vital contribution to this latent immune
      evasion. Lytic antigens may therefore be a key immune target. Investigations into
      a murine gamma-herpesvirus have now provided evidence that vaccination with
      apathogenic, latency-deficient mutants can largely protect against subsequent
      wild-type gamma-herpesvirus latency establishment.

PMID- 15245740
TI  - Immune control of herpes simplex virus during latency.
AB  - Herpes simplex virus type 1 (HSV-1) persists within the host in the presence of
      concomitant immunity by establishing a latent infection within sensory neurons.
      HSV-1 latency is widely viewed as a neuron-enforced quiescent state of the virus,
      in which a lack of viral protein synthesis prevents recognition of the infected
      neuron by the host immune system. On the basis of recent findings, however, we
      propose a more dynamic view of HSV-1 latency characterized by persistent or
      intermittent low-level viral gene expression in some latently infected neurons.
      We further propose that HSV-1-specific memory/effector CD8(+) T lymphocytes that
      are retained in the ganglion in close apposition to the neurons prevent full
      reactivation and virion formation through IFN-gamma production and an additional
      undefined mechanism(s).

PMID- 15245741
TI  - Mechanisms of HIV-1 escape from immune responses and antiretroviral drugs.
AB  - Despite the fact that HIV-1 induces vigorous antiviral immune responses, viral
      replication is never completely controlled in infected individuals. Recent
      studies have provided insight into the mechanisms by which focused immune
      pressure directed at particular B or T cell epitopes leads to the rapid
      appearance of escape mutations. Even if anti-HIV-1 immune responses could be
      enhanced to the point where they inhibit viral replication to the same extent as
      certain combinations of antiretroviral drugs, eradication would be unlikely
      because of the persistence of the virus in an extremely stable latent reservoir
      in resting memory CD4(+) T cells.

PMID- 15245742
TI  - Recent insights into HIV-1 Vif.
AB  - The lentiviruses, including HIV-1 (but excluding equine infectious anemia virus),
      encode a viral infectivity factor (Vif) protein. Circumstantial evidence
      suggested that Vif acts to neutralize an inhibitory host defense mechanism, but
      progress in the field was limited because the identity of the cellular target was
      unknown. The recent identification of the elusive host cell factor let loose a
      flood of advances. These findings have revealed a novel innate defense mechanism
      against retroviruses. In infected cells, the cellular cytidine deaminase
      APOBEC3G, a relative of the activation-induced deaminase (AID), is encapsidated
      into assembling virions. The enzyme lies in the virion, waiting to wreak havoc on
      the viral genome in the next round of virus replication--unless it is first
      caught by Vif.

PMID- 15245743
TI  - Toll-like receptors and microbes take aim at each other.
AB  - Toll-like receptors (TLRs) are key components of effective innate immunity. As
      such, pathogenic microorganisms must evade recognition by TLRs, manipulate the
      consequences of TLR activation, or contend with the inflammatory consequences of
      TLR activation. Recent studies have improved our understanding of the various
      mechanisms by which pathogenic organisms manipulate the TLR recognition system.

PMID- 15245744
TI  - Pathogens use carbohydrates to escape immunity induced by dendritic cells.
AB  - Dendritic cells (DCs) play a central role in balancing immune responses between
      tolerance induction and immune activation. Under steady state conditions DCs
      continuously sample antigens, leading to tolerance, whereas inflammatory
      conditions activate DCs, inducing immune activation. DCs express C-type lectin
      receptors (CLRs) for antigen capture and presentation, whereas Toll-like
      receptors (TLRs) are involved in pathogen recognition and DC activation. Recent
      data demonstrate that communication between TLRs and CLRs can affect the
      direction of immune responses. Several pathogens specifically target CLRs to
      subvert this communication to escape immune surveillance, either by inducing
      tolerance or skewing the protective immune responses.

PMID- 15245745
TI  - Visualizing the immune response to pathogens.
AB  - Advances in immune visualization have enabled the physical tracking of immune
      responses in vivo. The adaptation of such technology to models of infectious
      disease holds the promise of a more detailed analysis of host-pathogen
      interactions in a natural setting. However, the visualization of pathogen
      specific immune responses in vivo confronts challenges that are inherent to the
      study of infectious disease systems. Recent attempts to track pathogen-specific
      immune responses in vivo validate the usefulness and underline the complexity of
      this experimental strategy.

PMID- 15245746
TI  - New models for the study of Mycobacterium-host interactions.
AB  - The outcome of Mycobacterium infection is determined by a series of complex
      interactions between the bacteria and host immunity. Traditionally, mammalian
      models and cultured cells have been used to study these interactions. Recently,
      ameba (Dictyostelium), fruit flies (Drosophila) and zebrafish, amenable to
      forward genetic screens, have been developed as models for mycobacterial
      pathogenesis. Infection of these hosts with mycobacteria has allowed the
      dissection of intracellular trafficking pathways (Dictyostelium) and the roles of
      phagocytic versus antimicrobial peptide responses (Drosophila). Real-time
      visualization of the optically transparent zebrafish embryo/larva has elucidated
      mechanisms by which Mycobacterium-infected leukocytes migrate and subsequently
      aggregate into granulomas, the hallmark pathological structures of tuberculosis.

PMID- 15245747
TI  - Heat-shock proteins and the host-pathogen interaction during bacterial infection.
AB  - Heat-shock proteins (HSPs) are expressed at high levels by bacterial pathogens
      during adaptation to intracellular survival. Both host and pathogen heat-shock
      proteins contribute to immunity by receptor-mediated activation of the innate
      immune response and by participation in the presentation of antigens for the
      adaptive immune response. Manipulation of these interactions presents a potential
      route to improved control of infection by vaccination or immunotherapy.

PMID- 15245748
TI  - Mycobacterium leprae-induced demyelination: a model for early nerve degeneration.
AB  - The molecular events that occur at the early phase of many demyelinating
      neurodegenerative diseases are unknown. A recent demonstration of rapid
      demyelination and axonal injury induced by Mycobacterium leprae provides a model
      for elucidating the molecular events of early nerve degeneration which might be
      common to neurodegenerative diseases of both infectious origin and unknown
      etiology. The identification of the M. leprae-targeted Schwann cell receptor,
      dystroglycan, and its associated molecules in myelination, demyelination and
      axonal functions suggests a role for these molecules in early nerve degeneration.

PMID- 15245749
TI  - Immunity to West Nile virus.
AB  - Over the past five years, West Nile (WN) virus has emerged as an important public
      health concern in the United States. Recent studies from experimental models of
      WN virus infection have increased our understanding of its pathogenesis and
      immunity. These include the demonstration that the gene encoding 2'
      5'oligoadenylate synthetase is responsible for murine susceptibility to WN virus,
      the elucidation of the contributions of B, CD8(+) and gamma T cells in the
      control of murine WN virus infection, and the use of active immunization with
      envelope protein and passive transfer of immunoglobulin for immunotherapy. These
      efforts will facilitate the development of effective vaccines and therapies to
      combat WN virus.

PMID- 15245750
TI  - The strategies of the Theileria parasite: a new twist in host-pathogen
      interactions.
AB  - Theileria parasites infect and transform cells of the ruminant immune system.
      Continuous proliferation and survival of Theileria-transformed cells involves the
      well-orchestrated activation of several host-cell signalling pathways.
      Constitutive NF-kappa B (nuclear factor kappa B) activation is accomplished by
      recruiting the IKK (I kappa B kinase) complex, a central regulator of NF-kappa B
      pathways, to the surface of the transforming schizont, where it becomes
      permanently activated. Constitutive activation of the PI-3K-PKB [phosphoinositide
      3-kinase-(Akt) protein kinase B] pathway is likely to be indirect and is
      essential for continuous proliferation. Theileria-transformed T cells express a
      range of anti-apoptotic proteins that can be expected to provide protection
      against apoptosis induced by death receptors, as well as cellular control
      mechanisms that are mobilised to eliminate cells that entered a cycle of
      uncontrolled proliferation.

PMID- 15245751
TI  - Stress cytokines: pivotal proteins in immune regulatory networks; Opinion.
AB  - Stress proteins have three immunological regulatory functions: within the cell,
      on the cell membrane as signalling receptors, and in the extracellular
      environment as stress cytokines. They can activate the immune system by providing
      danger signals or they may downregulate immune and inflammatory responses. In
      addition, they can modulate immune responses by acting as chaperones for
      antigenic peptides while they themselves are processed and presented to T cells
      as self-peptides. We predict that the exploitation of the downregulatory
      properties of stress cytokines will have therapeutic applications in the
      treatment of human chronic inflammatory diseases, such as rheumatoid arthritis.

PMID- 15245752
TI  - Distinct efficacy of pre-differentiated versus intact fetal mesencephalon-derived
      human neural progenitor cells in alleviating rat model of Parkinson's disease.
AB  - Neural progenitor cells have shown the effectiveness in the treatment of
      Parkinson's disease, but the therapeutic efficacy remains variable. One of
      important factors that determine the efficacy is the necessity of pre
      differentiation of progenitor cells into dopaminergic neurons before
      transplantation. This study therefore investigated the therapeutic efficacy of
      mesencephalon-derived human neural progenitor cells with or without the pre
      differentiation in alleviating a rat model of Parkinson's disease. We found that
      a combination of 50 ng/ml fibroblast growth factor 8, 10 ng/ml glial cell line
      derived neurotrophic factor and 10 microM forskolin facilitated the
      differentiation of human fetal mesencephalic progenitor cells into dopaminergic
      neurons in vitro. More importantly, after transplanted into the striatum of
      parkinsonian rats, only pre-differentiated grafts resulted in an elevated
      production of dopamine in the transplanted site and the amelioration of
      behavioral impairments of the parkinsonian rats. Unlike pre-differentiated
      progenitors, grafted intact progenitors rarely differentiated into dopaminergic
      neurons in vivo and emigrated actively away from the transplanted site. These
      data demonstrates the importance of pre-differentiation of human progenitor cells
      before transplantation in enhancing therapeutic potency for Parkinson's disease.

PMID- 15245753
TI  - In vivo and in vitro effects of homocysteine on Na+, K+-ATPase activity in
      parietal, prefrontal and cingulate cortex of young rats.
AB  - In the present study we determined the effect of chronic administration of
      homocysteine on Na+,K+-ATPase activity in synaptic membranes from parietal,
      prefrontal and cingulate cortex of young rats. We also studied the in vitro
      effect of homocysteine on this enzyme activity and on some oxidative stress
      parameters, namely thiobarbituric acid-reactive substances (TBA-RS) and total
      radical-trapping antioxidant potential (TRAP) in the same cerebral structures.
      For the in vivo studies, we induced elevated levels of homocysteine in blood (500
      microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet
      tissue) of young rats by injecting subcutaneously homocysteine (0.3-0.6
      micromol/g of body weight) twice a day at 8 h intervals from the 6th to the 28th
      postpartum day. Controls received saline in the same volumes. Rats were killed 12
      h after the last injection. Chronic administration of homocysteine significantly
      decreased (50%) Na+,K+-ATPase activity in parietal, increased (36%) in prefrontal
      and did not alter in cingulate cortex of young rats. In vitro homocysteine
      decreased Na+,K+-ATPase activity and TRAP and increased TBA-RS in all cerebral
      structures studied. It is proposed that the alteration of Na+,K+-ATPase and
      induction of oxidative stress by homocysteine in cerebral cortex may be one of
      the mechanisms related to the neuronal dysfunction observed in human
      homocystinuria.

PMID- 15245754
TI  - Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate
      on brain Na+, K+-ATPase activity.
AB  - Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited
      neurometabolic disorder clinically characterized by epilepsy and mental
      retardation and biochemically by accumulation of guanidinoacetate (GAA) and
      depletion of creatine. Although the neurological symptoms are predominant, the
      pathogenesis of the brain dysfunction in this disorder is not yet established. In
      the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase
      and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young
      rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity
      without affecting Mg2+-ATPase activity. We also evaluated the effect of
      glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and
      taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH,
      trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L
      NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity.
      Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA
      is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane
      alteration. The present data may contribute to the understanding of the
      neurological dysfunction characteristic of GAMT-deficient patients.

PMID- 15245755
TI  - A quantitative study of the neuronal nitric oxide synthase expression in the
      superficial layers of the adult rat superior colliculus after perinatal
      enucleation.
AB  - The level of expression of the neuronal nitric oxide synthase (nNOS) in the
      retinorecipient layers of rat superior colliculus (SC) was investigated in adult
      rats after neonatal enucleation using two biochemical methods: (1) measurement of
      the in vitro specific-activity of NOS by the conversion of [3H]-arginine to [3H]
      citrulline and (2) immunochemical analysis by western blotting and densitometry
      of immunoreactive bands using antibodies that recognise the three prominent
      isoforms of nNOS, alpha, beta and gamma. A total of 20 Lister rats were used in
      this study. We have shown that the deprivation of the retinocollicular
      projections at early postnatal ages induces no significant change in the specific
      activity of nNOS. We also have shown that the deafferentation does not
      significantly influence either the total amount of nNOS in the SC superficial
      layers or the relative contribution ratio of nNOS isoforms. In conclusion, the
      expression and activity of nNOS in the SC retinorecipient layers was shown not to
      be dependent on the presence of retinal afferents during development.

PMID- 15245756
TI  - Stem/progenitor cells in the postnatal inner ear of the GFP-nestin transgenic
      mouse.
AB  - Nestin promoter-GFP (green fluorescent protein) transgenic mice were used to
      determine the presence of stem/progenitor cells in the mouse inner ear. We
      examined the inner ear of mice at the following postnatal days (P): P0, P4, P5,
      P15 and P60. Hair cells stereocilia were identified with the use of the
      histochemical marker phalloidin. Whole endorgans or cryosections were analyzed
      under epi-fluorescent or confocal microscopy. From P0 to P5, GFP expressing cells
      were found in the vestibular sensory epithelia of the macula utricle, but not in
      the crista ampullaris. Cells within the stroma (tissue underneath the sensory
      epithelia), utricle, and crista were also GFP-positive. Satellite cells in the
      vestibular ganglia were GFP-positive, while vestibular ganglia neurons were not.
      In the organ of Corti, GFP signal was found in inner border and inner phalangeal
      cells that surround the inner hair cells (GFP-negative), Dieters cells and cells
      in the great epithelial ridge. Outer hair cells were mildly positive for GFP.
      Satellite cells in the spiral ganglia were GFP-positive, while spiral ganglia
      neurons were not. Similar GFP expression was found in the vestibule and cochlea
      of animals at P15, however, outer hair cells showed no GFP expression. The inner
      ear of P60 animals contained moderate GFP expression in the stroma of the crista
      ampullaris and utricle, but not within the sensory epithelia. In the organ of
      Corti, moderate GFP expression was found in a few Deiters cells. The present data
      indicates that the expression of nestin in the mouse inner ear is developmentally
      regulated; yet in the adult inner ear there are some nestin expressing cells,
      suggesting an intrinsic repair potential, although to a more limited extent than
      during early post-natal life.

PMID- 15245757
TI  - MyoD-lacZ transgenes are early markers in the neural retina, but MyoD function
      appears to be inhibited in the developing retinal cells.
AB  - Recent findings suggest that eye and skeletal muscle development in vertebrates
      share the same regulatory network. In that network, Pax3 gene is apparently
      activated through Dach/Eya/Six feedback loop to mediate MyoD-driven myogenesis.
      The purpose of this study was to investigate previously reported MyoD-lacZ
      expression in the developing mouse neural retina and to gain insight into the
      potential role of MyoD in the embryonic retinal cells. The analysis of MD6.0-lacZ
      and 258/-2.5lacZ transgenic embryos revealed that the retinal temporal expression
      pattern of the two transgenes resembled their expression pattern in the MyoD
      dependent precursor muscle cells. However, MyoD transcripts and protein could not
      be found in the sites of MyoD-lacZ retinal expression. Furthermore, our
      immunohistochemical analysis suggests the existence of diverse factors (e.g.,
      Pax6 and Chx10) within the retinal cells that differentially and inappropriately
      activate the two transgenes. Finally, the retinal phenotype observed in Pax7-/-
      knock-out mice suggests a role for Pax7 in photoreceptor cell differentiation,
      retinal lamination and in the etiopathology of retinoblastoma. Taken together,
      our data suggest that the MyoD gene evolved a different mechanism to achieve its
      down-regulation within the retina than that of the Myf5 gene.

PMID- 15245758
TI  - Extracellular superoxide concentration increases following cerebral hypoxia but
      does not affect cerebral blood flow.
AB  - Abnormalities of cerebral blood flow during and following hypoxia and ischemia
      contribute to the progression of tissue injury. Oxidative stress during and
      following hypoxia is known to markedly increase superoxide anion concentration.
      There is conflicting evidence that the concentration of superoxide anion
      regulates cerebral blood flow through its effect on vascular tone, although
      difficulties in measurement of superoxide anion complicate these studies. In
      order to test the hypothesis that changes in cerebral blood flow during and
      following hypoxia are due to changes in extracellular superoxide anion levels, we
      examined tissue oxygen levels by fiberoptic oximetry and superoxide anion levels
      using a previously validated cytochrome c coated electrode on the cortical
      surface and correlated these measurements to cerebral blood flow measured by
      laser Doppler in rats subjected to 20 min of hypoxia followed by hyperoxic
      reoxygenation recovery. The results showed a burst of superoxide anion with the
      onset of reoxygenation that temporally correlated with a transient peak in tissue
      oxygen tension lasting 10 min. and was eliminated by pretreatment with Cu-Zn
      superoxide dismutase conjugated to polyethylene glycol. Cerebral blood flow did
      not differ during hypoxia or recovery in the polyethylene glycol conjugated
      superoxide dismutase and control treatment groups. This study demonstrated no
      effect of increased superoxide anion concentration on cerebral blood flow during
      hyperoxic recovery following hypoxia.

PMID- 15245759
TI  - Differences in cell migration of cultured pituitary cells from infantile and
      adult rats: participation of the extracellular matrix and epidermal growth
      factor.
AB  - During early postnatal development in the rat, the tissue architecture of the
      pituitary gland shows changes, revealing an intense migration process of the
      cells. The aim of this work was to examine anterior pituitary cell migration over
      type I and III collagen as well as type IV collagen, of cultured pituitary cells
      from infantile rats and adult rats, and the participation of the epidermal growth
      factor in this process. Differences in cell migration rate over these two types
      of collagen substrates were observed at both ages, and all in all, three times
      more cells migrated over type I/III collagen than over type IV collagen. These
      data show the migration-promoting role of type I/III collagen for pituitary
      cells. Furthermore, when infantile cells were challenged to migrate over bovine
      serum albumin, the migration rate diminished, and, on the contrary, adult cell
      migration was higher. However, over collagen, infantile cells increased their
      migration rate with epidermal growth factor stimulation and adult cells showed a
      decrease in migration when the growth factor was in the medium. During migration,
      pituitary cells associated and arranged in clusters. This behavior increased in
      the presence of epidermal growth factor in the infantile cultures. Moreover,
      epidermal growth-factor-stimulated infantile cells formed larger aggregates.
      Adult cells also showed associative behavior, but more cells were observed
      isolated than in cluster arrangements and the growth factor did not induce
      changes in this behavior. Results showed a difference in the response of cell
      migration and cell association capacity to epidermal growth factor after
      migration of infantile and adult pituitary cells. With these observations we
      propose that epidermal growth factor is a cell regulator of the pituitary tissue
      re-arrangement process during the infantile period.

PMID- 15245760
TI  - Sleep science 50 years after the discovery of REM sleep: contributions of the
      Italian Association of Sleep Medicine.

PMID- 15245761
TI  - Evidence for a fourth locus for autosomal dominant nocturnal frontal lobe
      epilepsy.
AB  - Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have
      been identified in two members of the neuronal nicotinic acetylcholine receptor
      gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for alpha4 and
      beta2 subunit, respectively. However, mutations in these genes account for only a
      minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome
      15q24 the gene was not identified. The involvement of the three loci in the
      pathogenesis of ADNFLE was investigated in 12 unrelated Italian families,
      selected on the basis of anamnestic and video-polysomnographic data. Compliant
      family members were typed for polymorphic markers spanning the analyzed
      chromosome regions. Linkage analyses excluded association of all chromosome
      regions with ADNFLE in 72% of cases. In two, four and one families it was
      impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3,
      respectively, however, no mutations have been detected in the nicotinic receptor
      genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and
      ENFL3 are minor loci for the disease and point to the existence of at least a
      fourth locus for ADNFLE.

PMID- 15245762
TI  - Mental activity after early afternoon nap awakenings in healthy subjects.
AB  - Despite the common misconception that rapid eye movement (REM) sleep is a unique
      correlate of dreaming, reports of mental activity can be elicited after
      awakenings from any stage of nocturnal sleep. We extended the investigation to
      naps and tried to explore the relationship between recall length and level of
      sleep stage and depth preceding the awakening. We hypothesized that dream report
      length would be related to arousal level. In 10 healthy young adults, sleep EEG
      and EOG were recorded for four non-consecutive early afternoon naps. Dream
      recalls were recorded following 10 s, 1 min, and 6 min of NREM Stage 2 and after
      5 min of first REM period. We measured mental recall with total word count (TWC)
      method, sleep stages by using EEG visual scoring and Delta and Beta activity by
      period amplitude (PAA) and power spectral (PSA) analyses. All awakening
      conditions were followed by a dream report. TWC was significantly greater after
      REM than after 10 s and 1 min of NREM, and TWC did not differ among the NREM
      awakenings. Delta activity after REM was significantly lower compared to the NREM
      6 and 1 min while Beta activity did not differ across the conditions. Assuming
      that arousal level decreased with increased NREM duration and increasing Delta
      EEG activity, the constant TWC across the three NREM awakenings indicates that
      arousal level cannot be the only factor affecting dream report length. Some other
      factor such as memory processing may explain the longer dream reports following
      REM sleep, or it may be that the EEG is an imperfect indicator of arousal level.

PMID- 15245763
TI  - Recurrent nightmares and disorders of arousal in temporal lobe epilepsy.
AB  - Sleep is known to be severely altered in temporal lobe epilepsy (TLE).
      Furthermore, sleep deprivation is one of the key factors contributing to
      cognitive deficits and drug resistance in TLE. In the past, "non-ictal"
      parasomnias, as well as parasomnia-like nocturnal episodes ultimately diagnosed
      as seizures, have been documented in epileptic patients. However, recurrence of
      possibly "ictal" parasomnias in TLE has not been adequately appreciated. Through
      questionnaires and diaries distributed to TLE patients and their families in a
      tertiary center for epilepsy, 20 out of 168 patients seen in the last 2 years
      have been identified as, probands and extensively recorded during sleep. Patients
      presented with confusional arousals were 16, 14 with nightmares, and 2 with sleep
      walking episodes. Episodes (25) corresponding to clinical or subclinical seizures
      have been video-polygraphically recorded in 10/20 patients. Therapy optimization,
      pharmacological or surgical, resolved the episodes in 17/20 patients. A better
      seizure control with improved quality of life can be achieved by increasing and
      extending the practice of nocturnal recording in TLE patients.

PMID- 15245764
TI  - Is insomnia a neurophysiological disorder? The role of sleep EEG microstructure.
AB  - Unlike other sleep disorders, such as sleep-related breathing disorders and
      periodic limb movement (PLM), the nature and severity of which are quantified by
      specific respiratory and motor indexes, no apparent organ dysfunction underlies
      several cases of insomnia (in particular primary insomnia), which can be
      objectively diagnosed only through the structural alterations of sleep.
      Polysomnography (PSG) investigation indicates that insomnia is the outcome of a
      neurophysiological disturbance that impairs the regulatory mechanisms of sleep
      control, including sleep duration, intensity, continuity and stability. In
      particular, analysis of sleep microstructure has permitted to establish that
      etiologic factors of different nature (including depressive disorders) exert a
      common destabilizing action on sleep, which is reflected in an increase of cyclic
      alternating pattern (CAP) rate. These premises allow us to attribute a more
      objective identity to insomnia, which risks otherwise to be considered as an
      unexplainable mental complaint. In conclusion, PSG remains the "gold standard"
      for measuring sleep, and especially insomnia.

PMID- 15245765
TI  - Insomnia, quality of life and psychopathological features.
AB  - Most of the studies about chronic insomnia focused only on specific features,
      providing in this way a partial outlook of the problem. The aim of this study was
      to examine a sample of chronic insomniacs from different points of view, by
      estimating the prevalence of stress, psychopathological symptoms, psychiatric
      disorders, changes in quality of life and illness behaviour. Forty-three patients
      (54.4%) experienced some psychosocial stressors in the last 6 months preceding
      the enrollment in the study. More than 55% of insomniacs reported symptoms of
      psychopathology. One or more than one psychiatric disorder was diagnosed in 61.5%
      of insomniacs. Life events could play a role in facilitating the transformation
      of a psychopathological symptom in a psychiatric disorder, since patients with a
      psychiatric diagnosis showed a higher percent of stress. The more noticeable
      disability in the group of insomniacs with psychiatric disorders and the absence
      of a corresponding worsening in illness behaviour suggests that insomniacs
      feelings about their health status are so negative to be not fatherly worsen by
      comorbidity in spite of a worsen disability. The evaluation of insomniacs should
      be as much detailed as possible, without neglecting tests for the evaluation of
      disability and illness behaviour, which are important not only for a correct
      diagnosis but also for monitoring the effects of therapies.

PMID- 15245766
TI  - Body movements during night sleep in healthy elderly subjects and their
      relationships with sleep stages.
AB  - In order to enlighten the profile of body movements during sleep at old age, the
      night sleep of twelve elderly subjects was polygraphically investigated; seven
      young healthy subjects were the control group. Significantly less body movements
      during sleep were found in the elderly compared to young subjects, meaning that
      the decrease in the number of body movements observed from infancy to childhood
      up to adulthood also continues at later ages. Differently from young adult, whose
      sleep body movements mainly occur in stage REM, no specific sleep state and/or
      stage was preferentially associated with the occurrence of body movements in the
      elderly. These data may point to an age-related modification in the interaction
      between motor cortex control and subcortical circuits. Furthermore, when body
      movements occur in elderly individuals, they are significantly more often
      followed in the next 60 s by a sleep stage change or by a spontaneous behavioural
      awakening. This might reflect a peculiar inability of elderly subjects to sustain
      stable states, and could also suggest that body movements may act as a co-factor
      in a process, comprising other physiological changes, leading to state shifts.

PMID- 15245767
TI  - Quantitative analysis of sleep EEG microstructure in the time-frequency domain.
AB  - A number of phasic events influence sleep quality and sleep macrostructure. The
      detection of arousals and the analysis of cyclic alternating patterns (CAP)
      support the evaluation of sleep fragmentation and instability. Sixteen
      polygraphic overnight recordings were visually inspected for conventional
      Rechtscaffen and Kales scoring, while arousals were detected following the
      criteria of the American Sleep Disorders Association (ASDA). Three
      electroencephalograph (EEG) segments were associated to each event, corresponding
      to background activity, pre-arousal period and arousal. The study was
      supplemented by the analysis of time-frequency distribution of EEG within each
      subtype of phase A in the CAP. The arousals were characterized by the increase of
      alpha and beta power with regard to background. Within NREM sleep most of the
      arousals were preceded by a transient increase of delta power. The time-frequency
      evolution of the phase A of the CAP sequence showed a strong prevalence of delta
      activity during the whole A1, but high amplitude delta waves were found also in
      the first 2/3 s of A2 and A3, followed by desynchronization. Our results
      underline the strict relationship between the ASDA arousals, and the subtype A2
      and A3 within the CAP: in both the association between a short sequence of
      transient slow waves and the successive increase of frequency and decrease of
      amplitude characterizes the arousal response.

PMID- 15245768
TI  - Dream experience during REM and NREM sleep of patients with complex partial
      seizures.
AB  - This study examined the effectiveness of the cognitive processes underlying
      dreaming in patients with complex partial seizures (CPS), by assessing the
      frequency of recall and the structural organization of dreams reported after
      awakenings provoked alternately during REM and stage 2 NREM sleep on 12
      cognitively unimpaired CPS-patients (six with epileptic focus in the right
      hemisphere and six in the left one). Each patient was recorded for three
      consecutive nights, respectively, for adaptation to the sleep laboratory context,
      for polysomnography and for dream collection. The frequency of dream recall was
      lower after stage 2 NREM sleep than REM sleep, regardless of the side of
      epileptic focus, while the length and structural organization of dreams did not
      significantly differ in REM and NREM sleep. However, the length of story-like
      dreams was influenced by global cognitive functioning during REM sleep. These
      findings indicate that in CPSs-patients the elaboration of dream experience is
      maintained in both REM and NREM sleep, while the access to information for
      conversion into dream contents and the consolidation of dream contents is much
      less effective during NREM rather than during REM sleep. Further studies may
      distinguish between these two possibilities and enlighten us as to whether the
      impaired memory functioning during NREM sleep is a side effect of anticonvulsant
      treatment.

PMID- 15245769
TI  - Validity of a short insomnia questionnaire: the SDQ.
AB  - The SDQ is a brief self-report insomnia questionnaire, which permits the rapid
      evaluation of insomnia based on the DSM-IV and ICSD-R criteria. The SDQ was
      developed to provide a fast and valid instrument both for the pre-screening of
      subjects who complain of insomnia and for epidemiological studies based on
      standardized definitions of this sleep disorder. Two studies were carried out in
      order to assess the validity of the SDQ as a self-report measure of insomnia. In
      the first study the convergent validity of the SDQ was assessed with respect to
      the global score of the Pittsburgh Sleep Quality Index (PSQI) in a sample of
      general practitioners' patients. The second study assessed the sensitivity and
      the specificity of the SDQ in discriminating between insomniacs or normal
      sleepers in a sample of college students who were given an extensive sleep
      evaluation within an insomnia counseling program. The SDQ classifications have a
      good convergent validity with the global sleep quality scores of the PSQI and its
      classifications of students who complain of or who do not complain of problems of
      insomnia have a sensitivity of 95% and a specificity of 87%. Results indicate
      that the SDQ is a valid paper and pencil instrument to screen insomnia.

PMID- 15245770
TI  - A driving simulation task: correlations with Multiple Sleep Latency Test.
AB  - Sleepiness and driving is a dangerous combination that causes thousands of
      crashes each year resulting in injury and death. In the last few years, driving
      simulators have been used to study the performance decrements associated with
      drowsiness. We correlated performances of a driving simulation task in healthy
      volunteers in different alertness conditions with objective (MSLT: Multiple Sleep
      Latency Test) and subjective (SSS: Stanford Sleepiness Scale; VAS: Visual
      Analogue Scale) sleepiness measurements. The subjects were tested on two days,
      after a normal night of sleep and after a night of complete sleep deprivation.
      The study consists of four sessions of MSLT, each one followed by subjective
      measurements of sleepiness and by a 30 min driving simulation task with a
      monotonous driving scenario. The parameters that correlate most highly with MSLT
      are the standard deviation of lane position, the mean RT, crash frequency and
      exceeding the speed limit frequency. The monotonous driving simulation we adopted
      showed strong correlations with MSLT and subjective sleepiness scales in healthy
      subjects and is suitable to evaluate excessive daytime sleepiness in patients.

PMID- 15245771
TI  - Reliability of a driving simulation task for evaluation of sleepiness.
AB  - Driving Simulators reproduce situations that require tracking and visual
      searching, the main features of real driving. This study measured the reliability
      of a monotonous driving scenario to detect the circadian variations of alertness
      in healthy subjects. Five men and five women underwent a monotonous 30 min
      driving simulation task every 2 h. Before each driving task subjects completed
      the Stanford Sleepiness Scale (SSS) and the Visual Analogue Scale (VAS) to
      correlate the subjective measurements of sleepiness to the objective data of the
      simulator. Driving performances deteriorated or improved according to the
      circadian variation of alertness. The scenario is suitable to detect the
      consequences of sleepiness related to the circadian variations of alertness. The
      standard deviation of lane position, comparing the differences among the 10 min
      blocks in each task is the parameter most significant for the evaluation of
      sleepiness.

PMID- 15245772
TI  - Rapid eye movement density shows trends across REM periods but is uncorrelated
      with NREM delta in young and elderly human subjects.
AB  - Saccade-like eye movements are the most prominent phasic component of rapid eye
      movement (REM) sleep. Eye movement density (EMD) appears to be negatively related
      to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to
      determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a)
      whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is
      increased by daytime naps; and (c) whether EMD patterns across sleep cycles
      differ in the two age groups. Subjects participated in four separate 2-day
      recording sessions, each consisting of a baseline night, a daytime nap, and post
      nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM.
      EMD was not correlated with rate of non rapid eye movement (NREM) delta
      production (power/min) in the baseline sleep of either group. Changes in EMD and
      delta power/min on post nap nights also were uncorrelated. These data indicate
      that very strong changes in sleep depth (state) are required to overcome the
      individual stability (traits) of NREM delta and eye movement density. ANOVA for
      EMD across REM periods 1-4 showed a significant cycle effect and a significant
      age x cycle interaction. These effects were mainly due to YNs having depressed
      EMD in the first REM period, likely due to the low arousal level early in sleep
      in these subjects. Compared with waking saccades the saccade eye movements of REM
      sleep have received little investigation. Further study of these movements could
      shed new light on neurophysiology of REM sleep. Such studies might also be
      clinically useful because the density of these movements appears to be related to
      depression and (independently) to cognitive function in individuals with brain
      impairment.

PMID- 15245773
TI  - Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of
      the uterine cervix: a systematic review.
AB  - We identified eight randomised control trials of hydroxyurea and radiation versus
      radiotherapy alone (six published in full and two abstracts). Most concluded that
      outcomes were improved by use of hydroxyurea. However, methodological problems
      associated with these trials included small sample size, a large number of
      patient exclusions post randomisation, differing outcome definitions, subgroup
      analyses of already small numbers of patients and questionable rules for
      censoring, particularly a failure to include treatment related deaths in the
      survival analysis. All but two studies were of less than 50 patients. Patients
      were excluded from some analyses for treatment related reasons. The exclusion of
      such patients undoubtedly altered the conclusions of the studies. Even if there
      was a survival advantage attributed to hydroxyurea, overall survival was somewhat
      poor. We found the evidence regarding the use of hydroxyurea and radiotherapy to
      be inadequate for assessing its role in the treatment of cervical cancer.

PMID- 15245774
TI  - Modulation of the blood-brain barrier in oncology: therapeutic opportunities for
      the treatment of brain tumours?
AB  - Systemically administered chemotherapy is not very effective in the treatment of
      primary or metastatic brain tumours. An important reason for this low efficacy is
      insufficient drug delivery to the tumour site due to the presence of the blood
      brain barrier (BBB). In this review, we give an overview of strategies that were
      tested to bypass the BBB or to increase its permeability for anticancer drugs.
      Local drug administration through intracerebral implants offers only little
      benefit to patients with brain tumours, probably due to the limited diffusion of
      the drugs in brain tissue. Temporary disruption of the BBB can be achieved with
      intracarotid infusions of hypertonic mannitol. This method has been used with
      some success; however, toxic side effects and the high complexity of the surgical
      procedure limit its usefulness. More recently, the use of the bradykinin agonist
      cereport was shown to be useful in preclinical studies, but unfortunately
      clinical studies did not show improved efficacy. Since P-glycoprotein in the BBB
      restricts the brain entry of many anticancer drugs, inhibition of this drug
      transporter may be an option for improved drug delivery to brain tumours. Pre
      clinical studies have shown the feasibility to enhance the penetration of
      paclitaxel into the brain by co-administration with a potent P-glycoprotein
      inhibitor and further clinical research is warranted.

PMID- 15245775
TI  - Hepatic arterial infusion chemotherapy for metastatic colorectal cancer: a
      concise overview.
AB  - Patients with colorectal cancer commonly succumb to the sequelae of hepatic
      metastases. Response to systemic therapy is inadequate. Hepatic arterial infusion
      (HAI) exposes liver metastases to high local concentrations of drug. Herein, we
      review the randomized trials of HAI in colorectal cancer. Data for this review
      were identified by searches of MEDLINE and references from relevant articles
      using the search terms "infusion intra-arterial" and "colorectal cancer."
      Abstracts and reports from meetings were included only when they related directly
      to previously published work. Only papers published in English between 1966 and
      2003 were included. Randomized trials (5-fluorouracil- (5-FU-) or
      fluordeoxyuridine- (FUDR-) based regimens) often demonstrated superior response
      rates for HAI as compared to systemic chemotherapy (primary treatment or post
      resection). Enhanced survival has, however, shown only when HAI was combined with
      systemic chemotherapy in the post-resection setting. For 5-FU-based and perhaps
      other regimens, randomized trials of combined regional and systemic therapy
      versus systemic treatment alone may be needed in order to determine whether or
      not there is a survival advantage after HAI in unresectable patients, as has been
      recently demonstrated in resectable patients. A variety of agents other than 5-FU
      have also been given by HAI to patients with liver metastases from diverse
      cancers. Such regional therapy often yields encouraging response rates and impact
      on survival therefore merits investigation.

PMID- 15245776
TI  - DT-diaphorase: a target for new anticancer drugs.
AB  - DT-diaphorase (DTD) is an obligate two-electron reductase which bioactivates
      chemotherapeutic quinones. DTD levels are elevated in a number of tumour types,
      including non-small cell lung carcinoma, colorectal carcinoma, liver cancers and
      breast carcinomas, when compared to the surrounding normal tissue. The
      differential in DTD between tumour and normal tissue should allow targeted
      activation of chemotherapeutic quinones in the tumour whilst minimising normal
      tissue toxicity. The prototypical bioreductive drug is Mitomycin C (MMC) which is
      widely used in clinical practice. However, MMC is actually a relatively poor
      substrate for DTD and its metabolism is pH-dependent. Other bioreductive drugs
      have failed because of poor solubility and inability to surpass other agents in
      use. RH1, a novel diaziridinylbenzoquinone, is a more efficient substrate for
      DTD. It has been demonstrated to have anti-tumour effects both in vitro and in
      vivo and demonstrates a relationship between DTD expression levels and drug
      response. RH1 has recently entered a phase I clinical trial in solid tumours
      under the auspices of Cancer Research UK. Recent work has demonstrated that DTD
      is present in the nucleus and is associated with both p53 and the heat shock
      protein, HSP-70. Furthermore, DTD is inducible by several non-toxic compounds and
      therefore much interest has focussed on increasing the differential in DTD levels
      between tumour and normal tissues.

PMID- 15245777
TI  - Molecular biology of sporadic gastric cancer: prognostic indicators and novel
      therapeutic approaches.
AB  - Both the availability of multiple treatment modalities and novel therapeutic
      targets make the correct prognostic stratification and the identification of
      truly predictive factors an issue of major debate in gastric cancer. Along with
      "classic" prognostic factors such as those related to the diffusion of the tumour
      at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes
      or distant metastases) or those concerning the pathologic characteristics of the
      tumour, other, innovative, factors should be considered if a better definition of
      the characteristics of the tumour is to be given. These biological factors are
      often derived from the genetic process, which is thought to represent a crucial
      step to gastric cancer (DNA copy number changes, microsatellite instability,
      thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2,
      COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative
      prognostic indicators can also be considered predictive of response to therapy as
      they are a molecular target either to chemotherapeutics (i.e., thymidilate
      synthase that is targeted by 5FU) or to a new class of antineoplastic molecules
      (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix
      metalloproteinases, EGFR and VEGFR by specific inhibitors).

PMID- 15245778
TI  - Histone deacetylase inhibitors--a new tool to treat cancer.
AB  - Transcriptional regulation in eukaryotes is a multilevel hierarchical process. It
      is becoming clear that higher-order chromatin structure, occurring via
      modifications of histones in their nucleosome structure, plays a crucial role in
      regulating gene expression, both in normal and pathological states. Deacetylation
      of histones by histone deacetylases (HDACs) modifies the chromatin from an open
      gene active euchromatin structure to a closed gene silenced heterochromatin
      structure. Several cancer promoting mutations and chromosomal translocations
      result in repression of transcription through abnormal recruitment and activation
      of HDACs, leading to neoplastic transformation. This is the rationale for the
      evolvement of HDAC inhibitors as a new class in cancer therapy. Trials have shown
      anti-proliferation effect of histone deacetylase inhibitors in cell culture,
      animal models and in human with both hematological and solid tumors. The exact
      mechanism by which histone deacetylase inhibitors exert their effect is still
      obscure. Reversal of the alteration in gene expression by fusion transcription
      factors or overexpressed repressors is just one of several possible explanations.
      The territory of heterochromatin in the vicinity of the nuclear periphery raised
      the possibility of involvement of nuclear envelope proteins in the regulation of
      transcription. Our laboratory is interested in the transcription repression
      mechanism induced by the nuclear envelope lamina associated polypeptide 2 (LAP2)
      family of proteins through chromatin modification. Here, we will describe the
      structure of the nucleosome, review regulation of gene expression by acetylation
      of histones and give an update on the current phase I and phase II clinical
      trials with histone deacetylase inhibitors.

PMID- 15245779
TI  - Post-operative chemotherapy improves disease-free survival, but not overall
      survival in people with oesophageal squamous cell carcinoma.

PMID- 15245780
TI  - Consolidation radiotherapy may improve outcomes in people with Hodgkin's disease
      achieving complete remission after combination chemotherapy.

PMID- 15245781
TI  - Autologous bone marrow transplantation improves disease free survival but not
      overall survival in people with acute myeloid leukaemia.

PMID- 15245782
TI  - The effect of feet position on orthostatic posture in a female sample group.
AB  - Until now, the feet position effect on orthostatic posture has been investigated
      only in male or mixed sample groups. However, literature reports gender
      differences on orthostatic equilibrium. In order to study the effect of feet
      position on females and to complete the previous works, we tested a homogenous
      female sample group with 16 feet positions. Most of our results are in agreement
      with those already observed in male or mixed sample groups. The increase of the
      base of support induces an improvement of the orthostatic balance mainly on the
      medio-lateral axis. The stabilizing effect of the inner feet distance increase is
      more important than the one of the angle. We also noticed that the mean center of
      pressure position is located on the subjects' right side.

PMID- 15245783
TI  - Magnetic field exposure saves rat cerebellar granule neurons from apoptosis in
      vitro.
AB  - Accumulating evidence demonstrates that extremely low frequency magnetic fields
      (ELF-MFs) are capable of modifying neuronal function. Here we examine the effect
      of ELF-MF exposure on neuronal apoptosis. For this purpose cerebellar granule
      neurons (CGNs) from postnatal rats were employed, which are known to undergo
      apoptosis under normal condition (5.4 mM K+) in vitro. Exposure to a rotating (50
      Hz) ELF-MF for 5 days saved immature CGNs from apoptosis and promoted survival at
      the flux density of 300 mT, whereas virtually no neuronal survival was observed
      without exposure (sham). The survival-promoting effect of ELF-MFs occurred in a
      manner that depended on the size of culture flasks, suggesting that induced
      current plays a role in this phenomenon. A maximal survival-promoting effect was
      comparable to that of membrane depolarization (25 mM K+) and greater than that of
      brain-derived neurotrophic factor (BDNF). These results imply that ELF-MFs may
      serve as a potential tool for manipulating neuronal death and/or survival.

PMID- 15245785
TI  - Psychopathological traits and 5-HT2A receptor promoter polymorphism (-1438 G/A)
      in patients suffering from Anorexia Nervosa and Bulimia Nervosa.
AB  - Various studies have evaluated the possible role of the -1438G/A polymorphism
      within the 5-HT2A receptor gene in the susceptibility to Eating Disorders (EDs).
      One hundred and forty-eight ED patients (EDp) and 89 control subjects were
      interviewed by means of the Eating Disorder Examination (EDE) and analyzed for
      distribution of the -1438G/A polymorphism. Patients with the AA genotype
      suffering from Anorexia Nervosa and Bulimia Nervosa showed higher Weight and
      Shape Concern (P = 0.003 and P = 0.010, respectively) scores and greater overall
      severity of the ED psychopathology (EDE total score) (P = 0.012). The obtained
      preliminary data suggest the use of dimensional psychopathological measures in ED
      genetic studies.

PMID- 15245784
TI  - Association of interferon-alpha-induced depression and improved treatment
      response in patients with hepatitis C.
AB  - Thirty-nine patients with hepatitis C viral infection on interferon-alpha (IFN
      alpha) therapy were monitored weekly using the Beck Depression Inventory (BDI).
      Thirteen of thirty-nine patients (33%) developed IFN-alpha-induced major
      depressive disorder (MDD). During the course of IFN-alpha therapy, patients who
      became depressed were treated with citalopram, a selective serotonin reuptake
      inhibitor (SSRI) antidepressant. Results indicated that: (1) IFN-alpha response
      rates were significantly higher in those patients who developed IFN-alpha-induced
      MDD than in those who did not (end-of-treatment response (ETR) rates: 61.5%
      versus 26.9% and sustained viral response (SVR) rates: 38.5% versus 11.5%), (2)
      male patients with ETR to IFN-alpha therapy were, on average, approximately 33
      pounds lighter in body weight than male patients who did not respond, and (3)
      gender, race, past history of MDD, and past history of substance abuse were not
      significantly associated with ETR. In conclusion, our findings suggest that IFN
      alpha-induced MDD may be a predictor of a positive response to IFN-alpha therapy,
      or an indication of optimal dosing.

PMID- 15245786
TI  - Changes of high-affinity choline transporter CHT1 mRNA expression during
      degeneration and regeneration of hypoglossal nerves in mice.
AB  - The high-affinity choline transporter CHT1 works for choline uptake in the
      presynaptic terminals of cholinergic neurons. We examined its expression in the
      hypoglossal nucleus after unilateral hypoglossal nerve transection in mice by
      fluorescent in situ hybridization. One week after axotomy, CHT1 mRNA expression
      was lost in all hypoglossal motoneurons in the lesioned side. Two weeks after
      axotomy, CHT1 mRNA started to be re-expressed in a few motoneurons that recovered
      connections to tongue muscles as revealed by retrograde labeling with Fast Blue.
      After 4 weeks, most of axotomized hypoglossal motoneurons were reconnected and re
      expressed CHT1 mRNA as strongly as control neurons, and the regenerating
      cholinergic axons established mature neuromuscular junctions. These results
      suggest that the establishment of motor innervation is critical for CHT1 mRNA
      expression in hypoglossal neurons after axotomy.

PMID- 15245787
TI  - Catalase activity in cerebellum, hippocampus, frontal cortex and striatum after
      status epilepticus induced by pilocarpine in Wistar rats.
AB  - The mechanism underlying the vulnerability of the brain to status epilepticus
      (SE) induced by pilocarpine remains unknown. Oxidative stress has been implicated
      in a variety of acute and chronic neurologic conditions, including SE. The
      present study was aimed at was investigating the changes in catalase activity
      after pilocarpine-induced seizures and SE. The Control group was treated with
      0.9% saline (NaCl, subcutaneously (s.c.)) and sacrificed 1h after the treatment.
      Another group was treated with pilocarpine (400 mg/kg, s.c., Pilocarpine group)
      and sacrificed 1h after treatment. The catalase activity in the cerebellum,
      hippocampus, frontal cortex and striatum of Wistar rats was determined. The
      results have shown that pilocarpine administration and resulting SE produced a
      significant increase in the catalase activity in the hippocampus (36%), striatum
      (31%) and frontal cortex (15%) of treated adult rats. Nevertheless, in the adult
      rat cerebellum after SE induced by pilocarpine no change was observed in the
      catalase activity. Our results demonstrated a direct evidence of an increase in
      the activity of the scavenging enzyme (catalase) in different cerebral structures
      during seizure activity that could be responsible for eliminating oxygen free
      radicals and might be one of the compensatory mechanisms to avoid the development
      of oxidative stress during the establishment of SE induced by pilocarpine. Our
      reports also indicate clear regional differences in the catalase activity caused
      by pilocarpine-induced seizures and SE and the hippocampus might be the principal
      area affected and cerebellum does not modify for this parameter studied during
      epileptic activity.

PMID- 15245788
TI  - Intranasal administration of human IL-6 increases the severity of chemically
      induced seizures in rats.
AB  - Here we study the role of a pleiotropic pro-inflammatory cytokine, interleukin-6
      (IL-6), in epilepsy. To examine this problem, we used human recombinant IL-6
      applied intranasally (400 ng/40 microl) to rats 1h before seizures induced by
      systemic injection of pentylenenetrazole (PTZ, 75 mg/kg). Overall, compared to
      the saline-treated control animals (n = 11 in each group), IL-6-treated rats
      demonstrated elevated levels of IL-6 in the frontal lobe (measured by ELISA) and
      increased severity of PTZ-induced seizures (shorter latency, longer duration and
      higher mortality). Our findings show that IL-6 plays a pro-convulsant role in the
      brain and suggest that the IL-6 system may be a novel target for the development
      of anticonvulsant drugs.

PMID- 15245789
TI  - The potent inducible nitric oxide synthase inhibitor ONO-1714 inhibits neuronal
      NOS and exerts antinociception in rats.
AB  - We evaluated if ONO-1714, known as an inducible nitric oxide synthase (iNOS)
      inhibitor, could inhibit neuronal NOS (nNOS) and exert antinociception. ONO-1714
      potently inhibited both crude rat cerebellar NOS and recombinant human nNOS in
      vitro. Systemic ONO-1714 at 1-10 mg/kg suppressed carrageenan-induced thermal
      hyperalgesia in rats, an effect being equivalent to the antinociception caused by
      L-NAME or 7-nitroindazole at 25 mg/kg. The same doses of ONO-1714 also caused
      hypertension. Intrathecal (i.t.) ONO-1714 potently reduced the hyperalgesia, the
      effective dose range (0.2-0.6 microg/rat) being much lower than the
      antinociceptive dose (150 microg/rat) of i.t. L-NAME. Thus, ONO-1714 is
      considered a potent inhibitor of nNOS in addition to iNOS. The distinct relative
      antinociceptive activities of systemic and i.t. ONO-1714 are attributable to its
      possible poor blood-brain barrier permeability.

PMID- 15245790
TI  - APOE promoter polymorphisms and dementia in the elderly.
AB  - Previous observations suggest a contribution of two APOE promoter polymorphisms (
      219 G/T and -491 A/T) in dementia. From two independent populations of elderly
      (mean age of 84 and 85 years old, respectively), we observed that subjects
      bearing the -219T allele were at increased risk of dementia (OR = 1.9 (95% CI,
      1.3-2.8), P = 0.0003) or AD (OR = 2.0 (95% CI, 1.2-3.4), P < 0.008). Conversely,
      the -491 A/T variant was not associated with this risk of dementia in the
      elderly, as previously described. Haplotype estimations including the two
      promoter and the coding APOE polymorphisms indicated that the -491A/-219T/4
      haplotype was at risk for the development of dementia (OR = 3.5 (95% CI, 2.5
      5.0), P < 0.0001), whereas the -491A/-219G/4 haplotype was not (OR = 1.1 (95% CI,
      0.6-2.1)). Similar results were observed when restricted to Alzheimer's disease.
      In conclusion, these data indicate that the -219 G/T polymorphism is a genetic
      determinant of dementia in the elderly, independently of the 4 allele.

PMID- 15245791
TI  - Season of birth effect on personality in a general population.
AB  - Seasonality of births in schizophrenia and other mental disorders has been
      consistently observed. This may be through effects of unknown environmental
      factors that seasonally fluctuate on the brain development. The effects may
      affect cognitive function of the brain and behavioral characteristics that might
      be correlated with the development of personality not only in patients with
      mental disorders but also in healthy subjects. We, therefore, investigated the
      effects of season of birth on personality traits in healthy Japanese adults (n =
      397). Personality traits were evaluated using the NEO Personality Inventory
      Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during
      winter (December to February) than other subjects was observed (P = 0.036, after
      correction for the multiple testing, multiple regression analysis adjusting for
      age and sex). Other major factors of the NEO PI-R, including Neuroticism,
      Extraversion, Openness and Conscientiousness, were not affected by season of
      birth. Further studies may be recommended to confirm the results, considering the
      relatively limited sample size. Evaluation of cognitive functions and behaviors
      using other measures including event-related potentials and functional MRI may
      also help the interpretation of the present result.

PMID- 15245792
TI  - Similar profiles in human period1 gene expression in peripheral mononuclear and
      polymorphonuclear cells.
AB  - Increasing amounts of data have indicated the physiological significance of
      circadian clock gene regulation in various peripheral cells. In the present
      study, we examined expression of the human homolog of period1 (hPer1) in
      peripheral mononuclear cells (MNCs) and polymorphonuclear neutrophils (PMNs) in
      seven healthy young male volunteers (mean age, 21.0 years; range, 19-24 years)
      under modified constant routine conditions. The expression of hPer1 as determined
      by real-time PCR with gene-specific hybriprobes in MNCs and PMNs showed
      significant daily variations with similar acrophases and peak transcription in
      the subjective morning. The acrophases in hPer1 expression rhythms in MNCs and
      PMNs were found to correlate positively with that of the serum melatonin
      secretion rhythms, which is a reliable phase marker of the suprachiasmatic
      nucleus (SCN), the circadian master clock. The present findings indicate that
      clock gene activity could be preserved across different peripheral blood cell
      types and support the assumption that peripheral clocks are entrained by the SCN.

PMID- 15245793
TI  - Contribution of the medial amygdaloid nucleus to the development of hypertension
      in spontaneously hypertensive rats.
AB  - We previously demonstrated involvement of the medial amygdaloid nucleus in
      restraint stress-induced pressor responses in rats. In this study, neuronal
      perikarya in the medial amygdaloid nucleus of 4-week-old spontaneously
      hypertensive rats (SHR) were selectively destroyed with ibotenic acid. Bilateral
      lesions of the medial amygdaloid nucleus attenuated the development of
      hypertension in SHR. Body weight gain was not different between lesioned and sham
      lesioned SHR throughout the experimental periods. These data suggest that neurons
      in the medial amygdaloid nucleus may be involved in the development of
      hypertension in SHR.

PMID- 15245794
TI  - Galantamine and memantine produce different degrees of neuroprotection in rat
      hippocampal slices subjected to oxygen-glucose deprivation.
AB  - Recent clinical trials have shown that galantamine is efficacious in the
      treatment of mild to moderate Alzheimer's and vascular dementia, and memantine in
      severe stages of these diseases. Hence, the hypothesis that these two drugs might
      exert different degrees of neuroprotection has been tested. Rat hippocampal
      slices were subjected to oxygen and glucose deprivation (OGD) and to a re
      oxygenation period. Neuronal damage was monitored using the lactate dehydrogenase
      (LDH) released into the Krebs-bicarbonate medium as an indicator. Galantamine, a
      mild acetylcholinesterase (AChE) blocker and nicotinic receptor modulator, given
      30 min before and during OGD plus re-oxygenation (1, 2 and 3 h) significantly
      reduced LDH release by around 50%. Galantamine 5 microM reduced LDH release
      significantly during the re-oxygenation period while at 15 microM it afforded
      significant reduction of LDH release both during OGD and re-oxygenation.
      Memantine, a reversible blocker of NMDA receptors, at 10 microM only
      significantly reduced (40%) LDH release after 3 h re-oxygenation. The classical
      NMDA blocker MK-801 reduced LDH released around 40% at 1 microM at all re
      oxygenation times studied. These data indicate that galantamine has a
      neuroprotective window against anoxia wider than memantine. Whether these
      differences can be clinically relevant remain to be studied in appropriate
      clinical trials.

PMID- 15245795
TI  - Cellular localization of TRPC3 channel in rat brain: preferential distribution to
      oligodendrocytes.
AB  - In the present work we describe the cellular localization of TRPC3 in non
      excitable cells as compared to the neurons in normal rat brain. We performed a
      double labeling study for TRPC3 and one of the following cell-specific markers:
      mouse anti-glial fibrillary acidic protein (GFAP) for astrocytes; mouse anti-RIP
      for oligodendrocytes, or mouse anti-OX42 for microglia, or mouse anti-NeUN for
      neuronal nuclei or mouse anti-tyrosine hydroxylase (TH) for detection of
      dopaminergic neurons of the substantia nigra. Our double label immunofluorescence
      study showed that that TRPC3 is mainly localized in oligodendrocytes. These
      result were confirmed by the electron microscopy study, which showed TRPC3
      immunoreactivity in oligodendrocytes. Consistent with the evidence that calcium
      homeostasis is important to oligodendrocytes for development, myelination, and
      demyelination [Microsc. Res. Tech. 52 (2001) 672], we can speculate that the
      distribution of TRPC3 in oligodendrocytes plays a role in myelination and or
      demyelination processes.

PMID- 15245796
TI  - The beta-subunit composition of nicotinic acetylcholine receptors in the neurons
      of the guinea pig inferior mesenteric ganglion.
AB  - The antibodies against synthetic (183-192) fragments of beta2- and beta4-subunits
      of rat neuronal nicotinic acetylcholine receptor were used to study a beta
      subunit composition of nicotinic receptors in the inferior mesenteric ganglion of
      the guinea pig by both immunocytochemical staining and blocking of excitatory
      postsynaptic potentials induced by electric stimulation of the pre-ganglionic
      nerve (intermesenteric trunk). The beta4-specific antibody stained 59.8 +/- 7.5%
      of neurons and inhibited the synaptic responses in all (n = 10) neurons studied
      by 25.5 +/- 1.8%. The beta2-specific antibody did not stain ganglionic neurons
      and did not affect the synaptic transmission. Taking into account the previously
      obtained data on the alpha-subunits found in this ganglion, it is concluded that
      the neurons of inferior mesenteric ganglion contain nicotinic receptors of
      alpha3(alpha5)beta4 subtypes involved in synaptic transmission through the
      intermesenteric tract.

PMID- 15245798
TI  - Cisatracurium, but not mivacurium, inhibits survival and axonal growth of
      neonatal and adult rat peripheral neurons in vitro.
AB  - Cisatracurium and mivacurium are widely used neuromuscular blocking drugs.
      Previous reports have indicated growth-inhibitory effects of cisatracurium, but
      not mivacurium, on two human cell lines in vitro. These effects were ascribed to
      oxidative stress elicited by acrylate esters formed during cisatracurium
      breakdown. The aim of the present study was to investigate whether these agents
      would possibly interfere with the peripheral nervous system. Survival and axonal
      growth of rat primary neurons obtained from the superior cervical sympathetic
      ganglion (SCG) or from the adult dorsal root ganglion (DRG) were investigated
      after treatment with cisatracurium or mivacurium at concentrations from 1 to 10
      microM for 24 h. Cisatracurium, but not mivacurium, significantly decreased
      neuronal survival in a dose-dependent manner, and axonal length was considerably
      reduced by cisatracurium as compared to controls. It is concluded that high
      concentrations of cisatracurium are potentially neurotoxic.

PMID- 15245797
TI  - Substance P potentiates 5-HT3 receptor-mediated current in rat trigeminal
      ganglion neurons.
AB  - The present study aimed to investigate the interaction between the coexistent SP
      receptor and 5-HT3 receptor in trigeminal ganglion (TG) neurons using whole-cell
      patch clamp technique. The majority of the neurons examined responded to 5-HT
      with an inward current (I5-HT) (78.2%, 79/101) that could be blocked by 5-HT3
      receptor antagonist, ICS-205,930. The I5-HT was potentiated by preapplication of
      SP (10(-10) to 10(-8) M) in most 5-HT-sensitive cells(78.5%, 62/79).
      Coapplication of SP and GR-82334, antagonist of NK1 receptor, had no enhancing
      effect on I5-HT. The concentration-response curves for 5-HT with and without SP
      preapplication show that: (1) the threshold 5-HT concentrations with and without
      SP preapplication are basically the same, while SP preapplication increased the
      maximal value of I5-HT by 38.0% of its control; (2) the EC50 values of the curves
      with and without SP pretreatment are very close, i.e. 1.89 x 10(-5) M and 2.08 x
      10(-5) M (P > 0.1; n = 9), respectively. Intracellular dialysis of GDP-beta-S, a
      non-hydrolyzable GDP analog, and GF-109203X, a selective protein kinase C
      inhibitor, removed the SP potentiation of I5-HT. These results may offer a clue
      to understanding the mechanism underlying the generation and/or regulation of
      peripheral pain caused by tissue damage inflammation, etc.

PMID- 15245800
TI  - Using the Unified Modelling Language (UML) to guide the systemic description of
      biological processes and systems.
AB  - One of the main issues in Systems Biology is to deal with semantic data
      integration. Previously, we examined the requirements for a reference conceptual
      model to guide semantic integration based on the systemic principles. In the
      present paper, we examine the usefulness of the Unified Modelling Language (UML)
      to describe and specify biological systems and processes. This makes unambiguous
      representations of biological systems, which would be suitable for translation
      into mathematical and computational formalisms, enabling analysis, simulation and
      prediction of these systems behaviours.

PMID- 15245801
TI  - Model validation of biological pathways using Petri nets--demonstrated for
      apoptosis.
AB  - This paper demonstrates the first steps of a new integrating methodology to
      develop and analyse models of biological pathways in a systematic manner using
      well established Petri net technologies. The whole approach comprises step-wise
      modelling, animation, model validation as well as qualitative and quantitative
      analysis for behaviour prediction. In this paper, the first phase is addressed
      how to develop and validate a qualitative model, which might be extended
      afterwards to a quantitative model. The example used in this paper is devoted to
      apoptosis, the genetically programmed cell death. Apoptosis is an essential part
      of normal physiology for most metazoan species. Disturbances in the apoptotic
      process could lead to several diseases. The signal transduction pathway of
      apoptosis includes highly complex mechanisms to control and execute programmed
      cell death. This paper explains how to model and validate this pathway using
      qualitative Petri nets. The results provide a mathematically unique and valid
      model enabling the confirmation of known properties as well as new insights in
      this pathway.

PMID- 15245802
TI  - Discrete event, multi-level simulation of metabolite channeling.
AB  - Typically differential equations are employed to simulate cellular dynamics. To
      develop a valid continuous model based on differential equations requires
      accurate parameter estimations; an accuracy which is often difficult to achieve,
      due to the lack of data. In addition, processes in metabolic pathways, e.g.
      metabolite channeling, seem to be of a rather qualitative and discrete nature.
      With respect to the available data and to the perception of the underlying
      system, a discrete rather than a continuous approach to modeling and simulation
      seems more adequate. A discrete approach does not necessarily imply a more
      abstract view on the system. If we move from macro to micro and multi-level
      modeling, aspects of subsystems and their interactions, which have been only
      implicitly represented, become an explicit part of the model. To start exploring
      discrete event phenomena within metabolite channeling we choose the tryptophan
      synthase. Based on a continuous macro model, a discrete event, multi-level model
      is developed which allows us to analyze the interrelation between structural and
      functional characteristics of the enzymes.

PMID- 15245803
TI  - Optimal sampling time selection for parameter estimation in dynamic pathway
      modeling.
AB  - Systems Biology is an emerging research area, which considers mathematical
      representations of inter- and intra-cellular dynamics. Among the many research
      problems that have been addressed, dynamic modeling of signal transduction
      pathways has received increasing attention. The usual approach to represent intra
      cellular dynamics are nonlinear, usually ordinary, differential equations. The
      purpose of the models is to test and generate hypothesis of specific pathways and
      it is therefore required to estimate model parameters from experimental data. The
      experiments to generate data are complex and expensive, as a consequence of which
      the time series available are usually rather short, with few if any replicates.
      Almost certainly, not all variables one would like to include in a model can be
      measured. Parameter estimation is therefore an important research problem in
      Systems Biology and the focus of this paper. In particular, we are interested in
      optimizing the sampling time selection in order to minimize the variance of the
      parameter estimation error. With few sampling time points feasible, their
      selection is of practical importance in experimental design. Finally, the
      theoretical results are supported with an application.

PMID- 15245804
TI  - Dynamic Bayesian network and nonparametric regression for nonlinear modeling of
      gene networks from time series gene expression data.
AB  - We propose a dynamic Bayesian network and nonparametric regression model for
      constructing a gene network from time series microarray gene expression data. The
      proposed method can overcome a shortcoming of the Bayesian network model in the
      sense of the construction of cyclic regulations. The proposed method can analyze
      the microarray data as a continuous data and can capture even nonlinear relations
      among genes. It can be expected that this model will give a deeper insight into
      complicated biological systems. We also derive a new criterion for evaluating an
      estimated network from Bayes approach. We conduct Monte Carlo experiments to
      examine the effectiveness of the proposed method. We also demonstrate the
      proposed method through the analysis of the Saccharomyces cerevisiae gene
      expression data.

PMID- 15245805
TI  - Evidence-based urology--a utopia?

PMID- 15245807
TI  - Hormonal replacement therapy for aging men? The debate goes on.

PMID- 15245806
TI  - EAU guidelines on diagnosis and treatment of upper urinary tract transitional
      cell carcinoma.
AB  - OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for
      diagnosis, therapy and follow-up of upper urinary tract transitional cell
      carcinoma (UUTT) patients were established. Criteria for recommendations are
      based of level 2 only, as large randomised clinical trials have not been
      performed in this type of disease. METHOD: A systematic literature research using
      Medline Services was conducted. References were weighted by a panel of experts.
      RESULTS: TNM classification 2002 is recommended. Recommendations are developed
      for diagnosis, radical and conservative treatment and for local chemo
      immunotherapy. Prognostic factors are defined. Recommendations for follow-up
      after different types of treatment are given.

PMID- 15245808
TI  - Regenerative medicine in andrology: Tissue engineering and gene therapy as
      potential treatment options for penile deformations and erectile dysfunction.
AB  - Tissue engineering and gene therapy are currently investigated in animal studies
      for reconstructing penile tissue or treating erectile dysfunction. This review
      aims to examine these experimental efforts from the last years and tries to give
      a brief introduction to the basic methodology of these new techniques from the
      field of regenerative medicine.

PMID- 15245809
TI  - Non-invasive urothelial neoplasms: according to the most recent WHO
      classification.
AB  - The key points of the latest World Health Organization (WHO) classification of
      non-invasive urothelial tumors are: the description of the categories has been
      expanded in the current version to improve their recognition; one group
      (papillary urothelial neoplasm of low malignant potential) with particularly good
      prognosis does not carry the label of 'cancer'; it avoids use of ambiguous
      grading such as grade 1/2 or 2/3 (according to the WHO classification published
      in 1973, i.e., 1973 WHO classification); the group of non-invasive high grade
      carcinoma is large enough to contain virtually all those tumors that have
      biological properties (and a high level of genetic instability) similar to those
      seen in invasive urothelial carcinoma. This scheme is meant to replace the 1973
      WHO classification. Changes in classification have their own inherent problems,
      tending to lead to confusion, at least for a period of time. From the practical
      point of view, the use of both the 1973 and the latest WHO classifications is
      recommended until the latter is sufficiently validated.

PMID- 15245810
TI  - Handling and pathology reporting of prostate biopsies.
AB  - Appropriate handling and processing of prostate needle biopsies is critical for
      an optimal examination by pathologists. Reporting by pathologists should be
      accurate, unequivocal and concise, giving the information needed for the
      urologist. Quality parameters need to be developed to survey the performance of
      pathology laboratories.

PMID- 15245811
TI  - DD3PCA3 RNA analysis in urine--a new perspective for detecting prostate cancer.
AB  - OBJECTIVES: Serum tPSA lacks specificity. The DD3(PCA3) gene is highly specific
      for prostate cancer and is detectable in prostate cancer cells shed into urine
      after rectal palpation. A newly developed nucleic acid sequence based
      amplification assay (uPM3) for detecting DD3(PCA3) RNA in urine samples was
      evaluated prospectively in patients referred for prostate cancer detection.
      METHODS: The uPM3 assay simultaneously detects the relative expression of
      DD3(PCA3) RNA and PSAmRNA as a marker for prostate cells in urine. Urine samples
      were collected after attentive digital rectal palpation prior to transrectal
      guided prostate biopsy. Samples were provided as a single void specimen (20-30
      ml), stabilized in phosphate buffer and centrifuged. Lysis was performed on cell
      pellets DD3(PCA3) RNA and PSAmRNA were extracted and amplification was performed
      using isothermic nucleic acid based amplification (NASBA). The two targets were
      detected in real-time using specific beacons as probes in a thermostated
      spectrofluorimeter. Parameters of the amplification curve were defined after a
      logistic curve fitting routine and a classification tree model was constructed to
      predict the outcome of patients (i.e. cancer and non-cancer). RESULTS: 201
      patients were included in this prospective study. 158/201 analyzed urine samples
      contained enough prostate cells sufficient for DD3(PCA3) analysis (79% adequacy
      rate). Prostate cancer was found in 62 (39%) of the evaluable patients. Overall
      sensitivity, specificity, positive predictive value and negative predictive value
      for the uPM3 assay at a cut-off 0.5 probability were 82%, 76%, 67% and 87%
      respectively as compared to 98%, 5%, 40% and 83% respectively for tPSA (at a
      cutoff of 2.5 ng/ml). In the tPSA categories <4, 4-10 and >10 ng/ml sensitivity
      was 73%, 84% and 84% and specificity was 61%, 80% and 70%, respectively. The AUC
      (area under the curve) was 0.87 (CI 0.81-0.92). CONCLUSION: The uPM3 assay showed
      excellent clinical performances and a specificity far superior to tPSA.

PMID- 15245812
TI  - Erectile and urinary dysfunction after radical prostatectomy for prostate cancer
      in Quebec: a population-based study of 2415 men.
AB  - OBJECTIVE: To assess and quantify urinary and sexual function outcomes from a
      large scale cohort of Canadian men treated for localized prostate cancer.
      METHODS: A self-administered survey focusing on erectile (ED) and urinary
      dysfunction (UD) was completed by 2415 of 4546 men (response rate 53.1%) treated
      with prostatectomy for prostate cancer in the Province of Quebec between 1988 and
      1996. The time between treatment and survey completion ranged from 17 months to
      8.5 years. RESULTS: After prostatectomy, of 2227 men without ED before surgery,
      erections of adequate firmness for intercourse were reported by 25%. ED rate
      increased with age and ranged from 55% in men aged <60 years to 85% in men 75
      years or older. Of all, 19.1% reported ED treatment. ED rate was significantly
      related to UD severity. Severe UD, quantified as urinary leakage exceeding one
      tablespoon, was reported by 6.6%. Severe UD rate ranged from 4% in men aged <60
      years to 10% in men 75 years or older. Strictures were reported by 16.3% and were
      associated with a two-fold increase in severe UD rate (p<0.001). Finally, age and
      socioeconomic status represented important predictor variables in univariate and
      multivariate regression models. CONCLUSION: ED rate of 75% and severe UD rate of
      6.6% could be anticipated after RP. These outcomes are similar to unselected
      large scale, patient reported outcomes from the United States.

PMID- 15245813
TI  - Neutral third party versus treating institution for evaluating quality of life
      after radical cystectomy.
AB  - OBJECTIVE: To evaluate the possible impact of a neutral third party on the
      patients' responses to health-related quality of life (HRQL) instruments.
      METHODS: 119 patients operated at the Department of Urology in Lund with radical
      cystectomy and continent urinary tract reconstruction (continent cutaneous
      diversion or orthotopic bladder substitution) for locally advanced bladder cancer
      were included in the study. They were randomly divided in two groups, similar
      with regard to gender, age, length of follow-up, and type of reconstruction. The
      EORTC instruments QLQ-C30 and QLQ-BLM30 were sent to the patients. One group;
      "Lund patients", received the instruments from the Department of Urology in Lund,
      while the other group; "Stockholm patients", received the instruments from a
      neutral third party, i.e. "The Project Health and Well-Being" at the Karolinska
      Institutet in Stockholm. RESULTS: Response rates were high in both groups, 59 out
      of 60 among Lund patients and 57 out of 59 among Stockholm patients. There were
      statistically significantly more bowel problems reported in the Stockholm
      patients than in the Lund patients (p<0.05) in the QLQ-C30 instrument. Regarding
      type of reconstruction, the Stockholm patients with continent cutaneous diversion
      scored higher for constipation than the Lund patients (p<0.05), and the Stockholm
      patients with bladder substitution scored lower for emotional functioning and
      higher for dyspnoea and economical problems than the Lund patients (p<0.05. There
      were no statistically significant differences between the Lund patients and the
      Stockholm patients in the QLQ-BLM30 instrument. CONCLUSION: Though few factors
      differed between the two groups, the results may indicate that different results
      are obtained when a study is totally administered and analyzed by a neutral third
      party as compared with the surgeon or his or her institution. Larger studies are
      needed to further test this hypothesis.

PMID- 15245814
TI  - Hypoxia-inducible factor 1 alpha expression correlates with angiogenesis and
      unfavorable prognosis in bladder cancer.
AB  - INTRODUCTION AND OBJECTIVES: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a
      critical regulatory protein of cellular response to hypoxia and is closely
      related to the triggering of the angiogenic process. We examined the relationship
      between hypoxia and angiogenesis, as well as their prognostic impact in patients
      with urothelial bladder cancer. METHODS: The immunohistochemical expression of
      HIF-1 alpha was evaluated in 93 formalin-fixed paraffin-embedded primary
      transitional cell carcinoma tissue samples. HIF-1 alpha was recognized through
      nuclear staining of positive cells. The angiogenic profile was individually
      assessed immunohistochemically using a monoclonal antibody to vascular
      endothelial growth factor (VEGF) and microvessel density (MVD) was calculated
      with immunohistochemical staining of the adhesion molecule CD31 of the
      endothelial cells. RESULTS: A significant positive association between HIF-1
      alpha immunoreactivity and histological grade (p=0.009) was found. VEGF and MVD
      were closely related to tumor grade (p=0.06 and p<0.001) and clinical stage
      (p=0.04 and p<0.01, respectively). HIF-1 alpha was significantly correlated with
      VEGF expression (p=0.01) and MVD (p<0.001). Patients characterized by HIF-1 alpha
      overexpression had significantly worse overall (p=0.009) and disease-free
      survival (p=0.03). When HIF-1 alpha, histologic grade and stage were included in
      multivariate Cox regression analysis, HIF-1 alpha emerged as an independent
      prognostic factor (p=0.02) along with grade and stage, but lost its independent
      prognostic value after the inclusion of angiogenic factors in the multivariate
      model. In the subgroup of patients with T1 disease, HIF-1 alpha emerged as a
      significant negative predictor of the time to first recurrence. CONCLUSIONS: HIF
      1 alpha and angiogenesis markers may play an important predictive and prognostic
      role in patients with bladder cancer. HIF-1 alpha may be of biologic and clinical
      value as its overexpression is related to up-regulation of VEGF, the stimulation
      of angiogenesis and worse prognosis.

PMID- 15245815
TI  - Long-term efficacy of two cycles of BEP regimen in high-risk stage I
      nonseminomatous testicular germ cell tumors with embryonal carcinoma and/or
      vascular invasion.
AB  - OBJECTIVES: To report the long-term impact of two cycles of adjuvant chemotherapy
      on relapse rates and treatment-related morbidity in high-risk stage I
      nonseminomatous testicular germ cell tumors (NSGCTT I). MATERIAL AND METHODS:
      From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of
      vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen
      were treated with two courses of bleomycin, cisplatin, and etoposide (BEP).
      RESULTS: All patients but one (incidental death) were alive after an extended
      follow-up (median 113.2 months, range 63-189). No patients relapsed but two
      patients presented a second cancer in the remaining testis. Short-term toxicity
      was minimal and no long-term toxicity was observed. CONCLUSION: The present
      series, with extensive follow-up, demonstrated that the efficacy and toxicity of
      two cycles of BEP compared well with the results of surveillance strategies or
      RPLND in high-risk stage I NSGCTT.

PMID- 15245817
TI  - Organic, relational and psychological factors in erectile dysfunction in men with
      diabetes mellitus.
AB  - INTRODUCTION AND OBJECTIVES: Diabetes mellitus-induced erectile dysfunction
      (DMED) is thought to be multifactorial in aetiology and to include vascular,
      neurological, and psychological components. The aim of the present study is to
      determine the contribution of organic, relational, and intrapsychic components to
      the pathogenesis of ED in diabetic in comparison with non-diabetic patients.
      METHODS: We studied a consecutive series of 1027 using SIEDY structured
      interview. A complete physical examination and a series of metabolic,
      biochemical, hormonal, psychometric, penile vascular tests and nocturnal penile
      tumescence and rigidity evaluations were performed. RESULTS: 15% of patient
      studied were affected by DMED. Diabetic patients with DMED have a greater
      severity of erectile dysfunction and are more likely to have an organic, rather
      than an intrapsychic, component. Impaired sexual desire is less frequent in these
      patients and they had an higher prevalence of hypogonadism than non-diabetic
      individuals. CONCLUSION: Diabetic patients seeking treatment for erectile
      dysfunction have a greater severity of disease, less impaired sexual desire,
      suggesting that the need for medical care in diabetic patients with ED could be
      even greater than in their non-diabetic counterparts. Considering the higher
      prevalence of obesity-related decrease of testosterone levels in DMED, an
      appropriate screening and treatment of hypogonadism might improve the outcome of
      pharmacotherapy for ED in diabetic patients.

PMID- 15245816
TI  - Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third
      line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a
      phase II study.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of the combination of
      oxaliplatin and irinotecan in patients with relapsed or cisplatin-refractory germ
      cell tumors (GCT). PATIENTS AND METHODS: Eighteen patients with relapsed or
      cisplatin-refractory GCT were treated with oxaliplatin 85 mg/m(2) on days 1 and
      15, followed by irinotecan 80 mg/m(2) on days 1, 8 and 15, every four weeks for a
      maximum of six cycles. RESULTS: All patients were assessable for response and
      toxicity. Overall, 7 patients (40%) achieved a favorable response (4 complete and
      3 partial responses). One of the complete responders relapsed after 2.5 months
      and despite further treatment with high dose chemotherapy, he died two months
      later. The remaining 3 patients are continuously disease free for 11+, 14+ and
      19+ months. The partial responders subsequently progressed and died after 2, 3
      and 4.5 months, respectively. None of the patients with extragonadal mediastinal
      GCT responded to oxaliplatin and irinotecan chemotherapy. The investigated
      combination has a good tolerance. Neutropenia related toxicity (grade 3/4, 17%),
      neutropenic infections and sepsis were not common probably due to prophylactic
      use of hematopoietic colony stimulating factor (G-CSF). Thrombocytopenia and
      anemia were not a serious problem. Gastrointestinal side effects, specifically
      grade 3/4 diarrhea and nausea/vomiting were noted in 22% and 28% of patients,
      respectively. Oxaliplatin-associated neurotoxicity was rather low; grade 3
      peripheral sensory neuropathy was recorded in 11% of patients. CONCLUSION: The
      combination of oxaliplatin and irinotecan is feasible and associated with
      significant clinical antitumor activity, mild and manageable toxicity and easy
      outpatient administration in patients with relapsed or cisplatin-refractory germ
      cell cancer. This combination seems to offer a possibility for long-term disease
      free status (17%), despite the poor prognostic features of the study patient
      group.

PMID- 15245818
TI  - Lower urinary tract symptoms (LUTS) and sexual function in both sexes.
AB  - OBJECTIVES: It has been stated that lower urinary tract symptoms (LUTS) do not
      affect sexual function to any significant degree, but a recent study has
      suggested that there might be an association in men. The present study was
      conducted to investigate the relationship between LUTS and sexual problems in
      both men and women aged 40-65 years. METHODS: The survey was conducted in Denmark
      between May and June 2003. Detailed questionnaires were mailed to a random sample
      of 15,000 men and women aged 40-65 years. LUTS and sexual function were assessed
      by validated symptom scales. Multivariate regression analysis was performed using
      logistic regression for dichotomous dependent variables of sexual function. The
      independent variables for both sexes were age, LUTS, partner status, body mass
      index (BMI), alcohol consumption and co-morbidities. RESULTS: A total of 15,000
      questionnaires were mailed out, 8491 were completed and returned, and 7741 were
      deemed valuable and included in the analysis. LUTS and sexual dysfunction were
      common in both men and women. Logistic regression analysis of items related to
      erection problems and satisfaction with sex life in men and sexual function in
      women showed that LUTS are an independent risk factor for sexual dysfunction in
      both men and women aged 40-65 years. Significant effects on sexual function were
      also found for the independent variables of partner status and co-morbidities.
      CONCLUSIONS: The presence of LUTS is an independent risk factor for sexual
      dysfunction in men and women. These results highlight the clinical importance of
      evaluating LUTS in patients with sexual dysfunction, and the need to consider
      sexual issues in the management of patients with LUTS.

PMID- 15245819
TI  - The effect of tamsulosin on the resting tone and the contractile behaviour of the
      female urethra: a functional urodynamic study in healthy women.
AB  - AIMS: The aim of this functional urodynamic experiment was to study the effect of
      the selective alpha1(A)-blocker tamsulosin on the urethral pressure in healthy
      human females and assessed first the resting urethral pressure and second the
      urethral contractility in response to magnetic stimulation of the sacral roots.
      METHODS: 11 healthy female subjects gave their written informed consent and were
      included. A microtip pressure transducer catheter was inserted into the bladder
      and three baseline urethral pressure profiles were obtained. Another three
      urethral pressure profiles were recorded while magnetic single pulse stimulation
      of the sacral roots was performed above the motor threshold of the pelvic floor
      to evoke reproducible urethral contractions. Then the subjects received 0.4 mg of
      tamsulosin and the entire protocol was repeated 6 hours after drug
      administration. Cardiovascular monitoring was obtained during the baseline and
      follow-up measurements. Mean and maximal urethral pressure values calculated over
      the entire urethra, mean pressure values calculated over the proximal, middle and
      distal third of the urethra and the pressure amplitudes to magnetic stimulation
      at baseline were statistically compared to the follow-up measurements with
      tamsulosin. RESULTS: The oral administration of tamsulosin did not change the
      systemic blood pressure, but did significantly reduce the mean and maximal
      urethral pressure acquired over the entire urethra. When the proximal, middle and
      distal third of the urethra were analysed separately, there was a significant
      pressure reduction in all three segments. Amplitudes of the urethral contractions
      evoked by sacral magnetic stimulation remained unchanged after tamsulosin.
      CONCLUSIONS: These data show a significant relaxing effect of tamsulosin on the
      resting urethral tone in healthy females in vivo. These results may suggest
      tamsulosin as a new pharmacological approach to treat urinary retention due to
      overactive or non-relaxing urethra in women.

PMID- 15245820
TI  - Management of artificial urinary sphincter dysfunction.
AB  - OBJECTIVE: The long-term outcome of artificial urinary sphincter (AUS) is
      unpredictable because of, among others, the risk of breakdown of one of its
      components. Our objective was to define a strategy for an accurate diagnosis and
      an appropriate management of these problems. PATIENTS AND METHODS: From 1985 to
      2000, 298 AUS (AMS 800) have been implanted in 288 patients aged 53 +/- 21 years
      (8 to 87 years). There were 130 women with urinary stress incontinence, 84 with
      neurological disorders, 76 following prostatic surgery and 8 for other reasons.
      Diagnosis was often done following the recurrence of urinary incontinence. The
      pump was systematically checked and all patients underwent radiographic and
      urodynamic studies. We have systematically looked for the defective component in
      order to avoid replacing the entire sphincter. RESULTS: Fifty-five patients (19%)
      have been re-operated on after a median follow-up of 23 months (11 days-10
      years): Thirty-two only once, 20 twice and 3 patients 4 times. There were 55
      depressurizations, 18 device dysfunctions without depressurization and 11
      removals of the sphincter. Among the 55 depressurizations, 30 were related to a
      perforation of one component, 24 to a functional but insufficient sphincter and 1
      to tubing disconnection. In forty cases, only one component of the AUS was
      replaced while 2 components were replaced in 10 cases, the entire AUS in 4 cases
      and no component in one case. CONCLUSION: The longer the follow-up the greater is
      the probability of a dysfunction. We systematically continue to look for the
      defective component and just to replace it instead of the entire sphincter.

PMID- 15245821
TI  - P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the
      effect of intravesical resiniferatoxin.
AB  - OBJECTIVES: The ATP-gated purinergic receptor P2X3 is expressed by small diameter
      sensory neurons and has been identified in normal and neurogenic human bladder
      suburothelial fibres. Animal models have shown that ATP is released by the
      urothelium during bladder distension, suggesting a mechanosensory role for P2X3
      receptors in normal bladder function. Successful treatment of spinal neurogenic
      detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly
      acts on suburothelial C fibres, provides evidence for the emergence of a C fibre
      mediated spinal reflex. The aim of this study was to investigate the possible
      role of P2X3-positive innervation in this pathological voiding reflex by
      comparing suburothelial P2X3 immunoreactivity of controls and in patients with
      NDO before and after intravesical RTX. METHODS: Bladder biopsies were obtained
      from 8 controls and 20 patients with refractory NDO enrolled in a trial of
      intravesical RTX. P2X3 nerve fibre density and intensity were studied in the
      specimens by immunohistochemistry. RESULTS: P2X3-IR nerve fibres were
      significantly increased in patients with NDO compared to controls (p=0.014).
      Thirteen patients had pre- and post-RTX biopsies available for
      immunohistochemistry; 5 of them responded clinically and 8 were non-responders.
      In the 5 patients who responded to RTX, there was a significant decrease in P2X3
      positive fibres (p=0.032), whereas in non-responders, P2X3-IR nerve fibre density
      did not change significantly. CONCLUSIONS: In patients with NDO, the numbers of
      P2X3-IR nerve fibres were increased in the suburothelium. There was a significant
      decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential
      pathophysiological role for the P2X3 expressing fibres.

PMID- 15245822
TI  - Defining the components of a self-management programme for men with uncomplicated
      lower urinary tract symptoms: a consensus approach.
AB  - OBJECTIVE: To define the components of a self-management programme of lifestyle
      and behavioural interventions for symptom control in men with uncomplicated LUTS.
      The use of lifestyle and behavioural interventions for symptom control in men
      with uncomplicated LUTS is widespread in the UK, however the effectiveness of
      these interventions has never been formally evaluated. Defining the components of
      a self-management programme will allow effectiveness studies to take place.
      MATERIALS AND METHODS: An eight member multidisciplinary panel rated 94 items for
      their appropriateness to be incorporated into the self-management programme using
      The Research and Development Appropriateness Method--RAM (UCLA). The item list
      was developed using semi-structured interviews with health care professionals and
      a national UK practice survey. RAM is a formal consensus process where an expert
      panel rate items over two rounds. The first round is conducted by post and in the
      second round the panel meets to discuss their initial ratings chaired by an
      independent moderator, then a second and final vote is made. RESULTS: The panel
      agreed that 57 of the original 94 items were appropriate to be incorporated in
      the self-management programme. These interventions were contained within the
      following categories: patient assessment prior to starting a self-management
      programme (6), education and reassurance (4), fluid management (6), caffeine (4),
      alcohol (2), concurrent medication (2), types of toileting (2), bladder re
      training (15), miscellaneous (1), and implementation of a self-management
      programme (15). CONCLUSIONS: The components of a self-management programme of
      lifestyle and behavioural interventions for men with uncomplicated LUTS has been
      defined using the RAM consensus process. Now this problem of definition has been
      overcome, the effectiveness of self-management can be formally explored.

PMID- 15245823
TI  - Supra-ampullar cystectomy with preservation of sexual function and ileal
      orthotopic reservoir for bladder tumor: twenty years of experience.
AB  - OBJECTIVE: We describe the original surgical technique of supra-ampullar
      cystectomy associated with ileal neobladder, and present our results in terms of
      preservation of sexual potency, urinary continence and cancer control along
      twenty years of experience. MATERIALS AND METHODS: Twenty-eight consecutive
      patients with bladder tumor-27 transitional cell carcinomas (TCC) and 1
      leiomyosarcoma-underwent supra-ampullar cystectomy with ileal orthotopic
      neobladder (2 Camey I and 26 Camey II) between May 1984 and June 1999. The median
      age of the patients was 51.0 years (range 23-65). Preoperatively 24 patients had
      superficial high-risk TCC. Involvement of prostatic urethra was excluded by means
      of preoperative endoscopic biopsies. The bladder, part of the prostate with the
      prostatic urethra and regional lymph nodes were removed, while the vas deferens
      with deferential ampullae, seminal vesicles, ejaculatory ducts and the peripheral
      portion of the prostate were maintained. Median followup was 90.5 months (range
      10-228). RESULTS: Out of 28 patients 6 died of bladder cancer (all with
      metastases, 2 also with local recurrence); 4 out of the 22 patients who were free
      of disease at followup died of other causes. Potency was preserved in 26 patients
      (92.8%), reporting satisfactory sexual intercourses; 15 patients (53.5%) also
      maintained antegrade ejaculation allowing procreation in 3 cases. In one patient
      the orthotopic neobladder according to Camey I was converted into an ileal
      conduit because of the excessive capacity of the reservoir, high post-void
      residual and recurrent pyelonephritis. Of the remaining 27 patients 16 showed
      both daytime and nighttime urinary continence (average interval between
      micturitions = 3 hours), 6 were continent during the day and 5 performed self
      intermittent catheterization. CONCLUSION: Supra-ampullar cystectomy with
      detubularized ileal orthotopic neobladder allows to preserve sexual function in
      nearly all the cases and to maintain urinary continence in most patients, without
      compromising oncological outcome. The indication must be restricted to highly
      selected cases, without potential risk of local recurrences and concomitant
      prostatic carcinoma.

PMID- 15245824
TI  - Re: Hessels D, Klein Gunnewiek JMT, van Oort I, Karthaus HFM, van Leenders GJL,
      van Balken B, Kiemeney LA, Witjes JA, Schalken JA. DD3(PCA3)-based molecular
      urine analysis for the diagnosis of prostate cancer. Eur Urol 2003;44:8-16.

PMID- 15245825
TI  - Letter to the Editor; Re: Wirth MP, Weissbach L, Marx F-J, Heckl W, Jellinghaus
      W, Riedmiller H, Noack B, Hinke A, Froehner M. Prospective randomized trial
      comparing flutamide as adjuvant treatment versus observation after radical
      prostatectomy for locally advanced, lymph node-negative prostate cancer. Eur Urol
      2004;45:267-70.

PMID- 15245827
TI  - Religion and anxiety: a critical review of the literature.
AB  - Religion's effects on mental health have been debated for years, yet only in the
      last half century have these theories been empirically tested. While a number of
      mental health constructs have been linked to religion, one of the most prevalent
      and debilitating mental health indices, anxiety, has been largely ignored. This
      paper categorizes and critically reviews the current literature on religion and
      general indices of anxiety in terms of findings linking decreased anxiety to
      religiosity, increased anxiety to religiosity, and those finding no relation
      between anxiety and religiosity. Results from 17 studies are described and
      synthesized. Conceptual and methodological weaknesses that potentially threaten
      the validity and generalizability of the findings are discussed. Finally,
      conclusions and directions for future research are provided.

PMID- 15245828
TI  - Is cognitive behavior therapy developmentally appropriate for young children? A
      critical review of the evidence.
AB  - This paper questions the extent to which developmental considerations have been
      incorporated into the theory and practice of cognitive behavioral therapy (CBT).
      It focuses on children aged between 5 and 8 years because Piagetian developmental
      theory places them at a prelogical cognitive level, and thus, the use of a
      therapeutic approach that is based on a rationalist paradigm would be considered
      inappropriate. The cognitive demands made upon 5- to 8-year-old children by CBT
      are outlined, and the current developmental literature is reviewed in the light
      of this to evaluate the cognitive abilities of this age group. The models
      underpinning CBT are examined for evidence of the influence of developmental
      psychology, and the outcome literature of CBT techniques is then scrutinized to
      evaluate the efficacy of these techniques with young children. Conclusions are
      reached regarding the appropriateness of current cognitive-behavioral approaches
      with young children, and the implications for alternative approaches are briefly
      considered.

PMID- 15245829
TI  - Cognitive causes of social phobia: a critical appraisal.
AB  - This review examined critically studies issuing from the cognitive therapy (CT)
      model claiming to have unveiled cognitive causal factors of social phobia.
      Additionally, it examined outcome studies of CT-inspired interventions and other
      treatments having included measurements of cognitive constructs. Overall, we
      found no evidence consistently supporting the claim that social phobics are
      characterized by typical cognitive processes. Moreover, we found neither
      corroborating evidence for a controlling effect of such cognitive processes on
      social phobic conduct, nor consistent indications that cognitive therapies or
      techniques effect cognitive changes differently than other approaches. The
      evidence suggests rather, that cognitive factors change concurrently with other
      features of psychopathology as part of an overall improvement during or after
      effective therapy, regardless of therapeutic approach.

PMID- 15245830
TI  - Mutual influences on maternal depression and child adjustment problems.
AB  - Often undetected and poorly managed, maternal depression and child adjustment
      problems are common health problems and impose significant burden to society.
      Studies show evidence of mutual influences on maternal and child functioning,
      whereby depression in mothers increases risk of emotional and behavioral problems
      in children and vice versa. Biological mechanisms (genetics, in utero
      environment) mediate influences from mother to child, while psychosocial
      (attachment, child discipline, modeling, family functioning) and social capital
      (social resources, social support) mechanisms mediate transactional influences on
      maternal depression and child adjustment problems. Mutual family influences in
      the etiology and maintenance of psychological problems advance our understanding
      of pathways of risk and resilience and their implications for clinical
      interventions. This article explores the dynamic interplay of maternal and child
      distress and provides evidence for a biopsychosocial model of mediating factors
      with the aim of stimulating further research and contributing to more inclusive
      therapies for families.

PMID- 15245831
TI  - Models of adjustment to chronic illness: using the example of rheumatoid
      arthritis.
AB  - There are a number of theoretical frameworks that attempt to explain how
      individuals may adjust to threats to health and serious physical illness. The
      three major paradigms that attempt to organize key components of health and
      adaptation to illness include the following: the biomedical model which
      emphasizes disease; psychological models of adaptation to illness; and
      biopsychosocial models with the latter two emphasizing health, functioning, and
      well-being. Each of these three major paradigms, including biomedical,
      psychosocial, and biopsychosocial frameworks, is discussed and critiqued in turn,
      and contributions and theoretical issues in terms of adjustment to chronic
      illness, particularly rheumatoid arthritis (RA), are highlighted. Furthermore, a
      biopsychosocial framework for conceptualizing adjustment to physical illness is
      proposed that incorporates elements from key existing biomedical and psychosocial
      models of adaptation to chronic physical health issues.

PMID- 15245832
TI  - Virtual reality exposure therapy of anxiety disorders: a review.
AB  - Virtual reality exposure therapy (VRET) is an altered form of behavioral therapy
      and may be a possible alternative to standard in vivo exposure. Virtual reality
      integrates real-time computer graphics, body tracking devices, visual displays,
      and other sensory input devices to immerse patients in a computer-generated
      virtual environment. Research on this type of treatment for anxiety disorders is
      discussed in this article, and the mediating and moderating variables that
      influence VR treatment effectiveness as well. Evidence is found that VRET is
      effective for participants with fear of heights and of flying. For other phobias,
      research to date is not conclusive. More randomized clinical trials in which VRET
      is compared with standard exposure are required. Furthermore, studies are needed
      in which VRET is not just a component of the treatment package evaluated, but in
      which VRET should be assessed as a stand-alone treatment.

PMID- 15245833
TI  - A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus
      mechanisms.
AB  - Recently, experts have suggested that obsessive-compulsive disorder (OCD), a
      highly heterogeneous condition, is actually composed of distinct subtypes.
      Research to identify specific subtypes of OCD has focused primarily on symptom
      presentation. Subtype models have been proposed using factor analyses that yield
      dimensional systems of symptom categories, but not necessarily distinct subtypes.
      Other empirical work has considered the role of neuropsychological functioning
      and comorbidity as part of a comprehensive scheme for subtyping OCD. The
      identified dimensions from all of these studies have implications for the
      treatment of OCD. In this article, we review the research on subtypes of OCD,
      focusing on subtype schemes based upon overt symptom presentation and
      neuropsychological profiles. We also review research pertinent to alternative
      subtyping schemes, both conceptually and methodologically. The research is
      critically examined and implications for treatment are discussed. Recommendations
      for future investigations are offered.

PMID- 15245834
TI  - Psychological factors and cancer development: evidence after 30 years of
      research.
AB  - The question whether psychological factors affect cancer development has
      intrigued both researchers and patients. This review critically summarizes the
      findings of studies that have tried to answer this question in the past 30 years.
      Earlier reviews, including meta-analyses, covered only a limited number of
      studies, and included studies with a questionable design (group-comparison, cross
      sectional or semiprospective design). This review comprises only longitudinal,
      truly prospective studies (N=70). It was concluded that there is not any
      psychological factor for which an influence on cancer development has been
      convincingly demonstrated in a series of studies. Only in terms of 'an influence
      that cannot be totally dismissed,' some factors emerged as 'most promising':
      helplessness and repression seemed to contribute to an unfavorable prognosis,
      while denial/minimizing seemed to be associated with a favorable prognosis. Some,
      but even less convincing evidence, was found that having experienced loss events,
      a low level of social support, and chronic depression predict an unfavorable
      prognosis. The influences of life events (other than loss events), negative
      emotional states, fighting spirit, stoic acceptance/fatalism, active coping,
      personality factors, and locus of control are minor or absent. A methodological
      shortcoming is not to have investigated the interactive effect of psychological
      factors, demographic, and biomedical risk factors.

PMID- 15245835
TI  - The relations among depression in fathers, children's psychopathology, and father
      child conflict: a meta-analysis.
AB  - Research on parental depression is beginning to recognize the importance of
      studying fathers in relation to maladaptive outcomes in their offspring. Paternal
      depression is hypothesized to correlate with internalizing and externalizing
      psychopathology in children and adolescents and to compromise adaptive parent
      child relationships (e.g., increased conflict). In the present paper, meta
      analytic procedures were applied to this literature to address the magnitude and
      direction of covariation between paternal depression and children's functioning.
      In addition, we tested whether variation in findings could be accounted for by
      study characteristics. Results indicated that paternal depression was
      significantly related to offspring internalizing and externalizing
      psychopathology and father-child conflict. Larger effects for internalizing
      symptoms were associated with the use of community samples and symptom rating
      scales of internalizing problems.

PMID- 15245836
TI  - The transtheoretical model and motivational interviewing in the treatment of
      eating and weight disorders.
AB  - The transtheoretical stages of change model suffers from conceptual and empirical
      limitations, including problems of stage definition, measurement, and
      discreteness. Sequential transition across stages has not been established. The
      model lacks strong predictive utility, and there is little evidence that
      therapeutic interventions must be matched to stage to facilitate change. Initial
      tests applying the model to weight and eating disorders have been negative.
      Although the model is frequently associated with motivational interviewing (MI),
      no theory links the two. MI should be evaluated independently as a treatment for
      weight and eating disorders, to be used either alone or prior to treatments not
      explicitly addressing motivation. The conceptual compatibility and procedural
      overlap between cognitive behavioral therapy (CBT) and MI are analyzed.

PMID- 15245838
TI  - Ground based radon-222 observations and their application to atmospheric studies.
AB  - The aim of this paper is to review recent trends in the application of ground
      based radon observations to atmospheric research. In spite of over four decades
      of atmospheric radon monitoring, only in the past decade has the potential of
      this passive tracer been realised through a series of atmospheric model
      evaluation studies. Firstly, the key operational requirements for baseline radon
      detectors are briefly discussed, including lower limit of detection and response
      time. Then, current radon-related benchmarks for the evaluation of regional and
      global models are reviewed, with particular consideration given to the
      implications of data availability, resolution, site location and model
      spatial/temporal resolution. An 8-year subset of radon observations from the Cape
      Grim Baseline Air Pollution Station is used to suggest new benchmarks that
      exploit long-term data sets. Lastly an overview is presented of a technique that
      uses radon to estimate regional fluxes of climatically sensitive gases, with
      specific examples for CO2, CH4 and N2O.

PMID- 15245839
TI  - A radon and meteorological measurement network for the Alligator Rivers Region,
      Australia.
AB  - The network described in this paper has been set up to provide detailed time
      series data on concentrations of 222Rn in air at various locations within the
      Alligator Rivers Region, over a time frame of several years. These data will be
      important in assessing the effects of uranium mining operations on radon levels
      in the region, both in providing baseline and monitoring data and in calibrating
      and verifying predictive models. At present, three stations are operating in the
      region with a fourth being commissioned. Each station logs half hourly average
      radon concentrations and relevant meteorological data (wind speed, direction and
      variability, air pressure and temperature, relative humidity, soil temperature,
      rain and sunshine rates). It is intended to operate the four stations at selected
      locations for one- or two-year intervals, at the end of which three will be moved
      to new locations (one station at Mudginberri will be kept as a constant control
      station). Sites for which extensive datasets are currently available include:
      Jabiru Town, Jabiru East, Djarr Djarr, East Alligator Ranger Station and Nabarlek
      minesite. Illustrative data from these sites are presented.

PMID- 15245840
TI  - Uranium mine rehabilitation: the story of the South Alligator Valley
      intervention.
AB  - The rehabilitation of radioactively contaminated sites is an activity generally
      regarded with suspicion by the community. This is certainly the case for
      Australian Aboriginal traditional landowners. This paper describes the historical
      background to, and the successful development and implementation of, a
      consultation and planning process to rehabilitate former uranium mining and
      milling facilities on Aboriginal lands of the World Heritage-listed Kakadu
      National Park in northern Australia. The process of developing an appropriate
      community communication and consultation process to allay concerns about
      radioactivity is a cornerstone of the rehabilitation program. The initial stages
      of the program's implementation are also described. This program is also the
      first example of a radiological intervention under modern environmental and
      radiation protection legislation in the region. It was necessary to develop
      radiological standards for use in the program as none had been promulgated under
      existing relevant legislation.

PMID- 15245841
TI  - Quantifying the erosion processes and land-uses which dominate fine sediment
      supply to Moreton Bay, Southeast Queensland, Australia.
AB  - In this paper, the contributions from the three major erosion sources in the
      catchments of Moreton Bay are quantified, specifically for the <10 microm
      sediment size class. The erosion sources are classified as (i) sheet erosion from
      cultivated land, (ii) sheet erosion from uncultivated land, and (iii) subsoil
      erosion from gullies and channels. The catchments were the Brisbane and Logan
      rivers as well as the coastal catchments. A GIS based analysis of erosion risk
      was used to define areas of high erosion potential in each of the erosion source
      types. Radionuclide concentrations of 137Cs and 226Ra were measured on the <10
      microm fraction of eroding soils from these areas and then compared to
      concentrations on the same size fraction on deposited sediments within the
      rivers. A mixing model was then used to calculate the contributions from the
      different sources to the sediments. The contributions in the Brisbane and Logan
      catchments were found to be subsoil erosion (approximately 66 +/- 10%); sheet
      erosion from cultivated lands 33 +/- 10% and sheet erosion of uncultivated land 1
      +/- 10%. Surface and subsoil erosion contributions from the coastal catchments
      were found to be variable.

PMID- 15245842
TI  - 137Cs and excess 210Pb deposition patterns in estuarine and marine sediment in
      the central region of the Great Barrier Reef Lagoon, north-eastern Australia.
AB  - This paper focuses on the distribution of 137Cs and 210Pb(xs) in 51 estuarine and
      marine sediment cores collected between the Upstart Bay and Rockingham Bay in the
      Great Barrier Reef Lagoon, north-eastern Australia. Historical records of
      210Pb(xs) and 137Cs atmospheric deposition and present day terrestrial
      inventories in north-eastern Australia are presented. 210Pb(xs) and 137Cs fluxes
      measured on suspended sediments in the Burdekin River are considered to be a
      source of recent inputs of these nuclides to the nearshore region of this part of
      the Great Barrier Reef. Direct correlations between sediment nuclide inventories,
      maximum detectable depths, and sediment mass accumulation rates (MARs),
      calculated using both 137Cs and 210Pb(xs), are explored. In relation to
      inventories of 210Pb(xs), 60% of atmospheric fallout 137Cs appears to be missing
      from the sediments. The reasons for these differences in two tracers, primarily
      of atmospheric origin, are discussed in terms of the geochemical properties of
      these two nuclides. Evidence is presented to support the hypothesis that the
      137Cs distribution in these cores can be a useful independent tracer which
      provides confirmation of MARs calculated from the decay of 210Pb(xs).

PMID- 15245843
TI  - Biomagnification of 7Be, 234Th, and 228Ra in marine organisms near the northern
      Pacific coast of Japan.
AB  - Enrichment of natural radionuclides of thorium, radium and beryllium in several
      kinds of marine organisms was investigated near the Pacific coast of Miyagi
      Pref., Japan. The radioactivity of 7Be, 210Pb, 234Th, 238U, 228Ra and 137Cs was
      measured using gamma spectrometry. High concentrations of 234Th were observed in
      ascidian livers (50-400 Bq/kg dry) and excrement (2000-2900 Bq/kg dry), although
      the parent 238U concentrations were less than 3 Bq/kg dry. Such extreme
      disequilibrium between 238U and 234Th activity was observed in other organisms
      (barnacles, mussels and brown algae). Relatively high concentrations of 228Ra
      were detected in ascidian livers and were observed to decrease according to its
      half-life (5.75 year), suggesting disequilibrium with its parent 232Th. High
      concentrations (about 1900-5000 Bq/kg dry) of 7Be were detected in ascidian
      liver. Possible mechanisms for the observed biomagnification and bioaccumulation
      of these radionuclides in the organisms analyzed were proposed.

PMID- 15245844
TI  - Spatial distribution of 3H, 90Sr, 137Cs and (239,240)Pu in surface waters of the
      Pacific and Indian Oceans--GLOMARD database.
AB  - The data stored in the IAEA's Global Marine Radioactivity Database (GLOMARD)
      developed in the framework of the IAEA's project "Worldwide Marine Radioactivity
      Studies (WOMARS)" have been evaluated for Pacific and Indian Ocean surface
      waters. Four anthropogenic radionuclides-- 3H, 90Sr, 137Cs and (239,240)Pu --have
      been chosen as the most representative of anthropogenic radioactivity in the
      marine environment, comprising beta, gamma and alpha-emitters which are the most
      frequently analysed in the marine environment and which have (with the exception
      of tritium) the highest potential contribution to radiation doses to humans via
      seafood consumption. For the purposes of this study, the Pacific and Indian
      Oceans were divided into latitudinal boxes for which average radionuclide
      concentrations were estimated for the year 2000. The highest concentrations have
      been observed in the Japan Sea/East Sea and the North-West Pacific Ocean, the
      lowest in the Southern Ocean.

PMID- 15245845
TI  - 137Cs and (239+240)Pu levels in the Asia-Pacific regional seas.
AB  - 137Cs and (239+240)Pu data in seawater, sediment and biota from the regional seas
      of Asia-Pacific extending from 50 degrees N to 60 degrees S latitude and 60
      degrees E to 180 degrees E longitude based on the Asia-Pacific Marine
      Radioactivity Database (ASPAMARD) are presented and discussed. 137Cs levels in
      surface seawater have been declining to its present median value of about 3 Bq/m3
      due mainly to radioactive decay, transport processes, and the absence of new
      significant inputs. (239+240)Pu levels in surface seawater are much lower, with a
      median of about 6 mBq/m3. (239+240)Pu appears to be partly scavenged by particles
      and is therefore more readily transported down the water column. As with
      seawater, (239+240)Pu concentrations are lower than 137Cs in surface sediment.
      The median 137Cs concentration in surface sediment is 1.4 Bq/kg dry, while that
      of (239+240)Pu is only 0.2 Bq/kg dry. The vertical profiles of both 137Cs and
      (239+240)Pu in the sediment column of coastal areas are different from deep seas
      which can be attributed to the higher sedimentation rates and additional
      contribution of run-offs from terrestrial catchment areas in the coastal zone.
      Comparable data for biota are far less extensive than those for seawater and
      sediment. The median 137Cs concentration in fish (0.2 Bq/kg wet) is higher than
      in crustaceans (0.1 Bq/kg wet) or mollusks (0.1 Bq/kg wet). Benchmark values (as
      of 2001) for 137Cs and (239+240)Pu concentrations in seawater, sediment and biota
      are established to serve as reference values against which the impact of future
      anthropogenic inputs can be assessed. ASPAMARD represents one of the most
      comprehensive compilations of available data on 137Cs and (239+240)Pu in
      particular, and other anthropogenic as well as natural radionuclides in seawater,
      sediment and biota from the Asia-Pacific regional seas.

PMID- 15245847
TI  - Application of 210Pb-derived sedimentation rates and dinoflagellate cyst analyses
      in understanding Pyrodinium bahamense harmful algal blooms in Manila Bay and
      Malampaya Sound, Philippines.
AB  - The number of areas affected by toxic harmful algal bloom (HAB) in the
      Philippines has been increasing since its first recorded occurrence in 1983. Thus
      far, HAB has been reported in about 20 areas in the Philippines including major
      fishery production areas. The HAB-causing organism (Pyrodinium bahamense var.
      compressum) produces a cyst during its life cycle. Pyrodinium cysts which are
      deposited in the sediment column may play a role in initiating a toxic bloom.
      210Pb-derived sedimentation rate studies in the two important fishing grounds of
      Manila Bay and Malampaya Sound, Palawan have shown that Pyrodinium cysts may have
      been present in the sediment even before the first recorded toxic algal bloom in
      these areas. High sedimentation rates (approximately 1 cm/year) have been
      observed in the northern and western parts of Manila Bay. The results indicate
      that the sedimentation processes occurring in these bays would require subsurface
      cyst concentration analysis in evaluating the potential of an area to act as seed
      bed.

PMID- 15245846
TI  - 210Pb geochronology and trace metal fluxes (Cd, Cu and Pb) in the Gulf of
      Tehuantepec, South Pacific of Mexico.
AB  - Distributions of Al, Cd, Cu, Fe, Li, Mn and Pb were analyzed in a sediment core
      collected in the Gulf of Tehuantepec, an important fisheries region located in
      the South Pacific of Mexico, where data on metal accumulation and accretion rates
      were previously almost nonexistent. Depth profiles of metal concentrations were
      converted to time-based profiles by using a 210Pb-derived vertical accretion
      rate, estimated to be 0.05 cm year(-1) on the average. Sediments were dated up to
      8 cm depth, corresponding to a layer of ca. 140 years old. The historical changes
      of metal accumulation along the sediment core have shown a moderate enrichment of
      Cd, Cu and Pb concentrations at present, of about threefold the corresponding
      background concentrations. Chronological trace metal records showed that metal
      fluxes have increased over the last 20 years, reaching the maximum values at
      present of 2.5, 22.5 and 45.8 (microg cm(-2) year(-1)) for Cd, Pb and Cu,
      respectively. These increments in metal fluxes are likely influenced by the
      development of anthropogenic land-based activities since over this period of time
      oil production activities in the region have had a significant development.

PMID- 15245848
TI  - Using radiotracer techniques for coastal hydrodynamic model evaluation.
AB  - A three-dimensional (3D) water circulation and contaminant transport model of
      Manila Bay has been developed with the aim of better understanding the formation
      and movement of harmful algal blooms. Radiotracer techniques were used to
      evaluate the model by recording the dispersion of a tracer at depths of 2 and 15
      m near the injection point. The selected tracer was 99mTc eluted from a
      molybdenum/technetium medical generator. The rationale for the choice of the
      tracer and the location of the injection is discussed. At 2 m the transport was
      dominated by the prevailing winds, and at 15 m by tidally induced currents. The
      development of the hydrodynamic model and its experimental evaluation were
      iterative processes. The experimental study confirmed the need for full 3D
      modelling of Manila Bay; quantified the impact of the prevailing wind field on
      contaminant dispersion near the injection point; and allowed the calculation of
      transverse dispersivity to guide the selection of parameter values used in the
      overall model.

PMID- 15245849
TI  - Development and performance of the vehicle-mounted radiation monitoring equipment
      used in the Maralinga rehabilitation project.
AB  - The rehabilitation of the former nuclear test site at Maralinga involved (among
      other processes) the removal of contaminated soil from an area of approximately
      2.5 km2. The two most stringent rehabilitation criteria required measurements to
      ensure that no radioactive particle exceeding 100 kBq of 241Am activity, and no
      area of 1 ha exceeding 3 kBq/m2 of 241Am activity, remained in the rehabilitated
      area. The project timetable required that the area be scanned at the rate of
      approximately 3 ha/day. Two vehicle-mounted detection systems were developed and
      constructed to obtain the necessary measurements in the available timeframe. The
      scientific basis for the designs are presented, together with details of the
      selected equipment and technical solutions found. The performance of this
      equipment in the field is discussed in terms of both its scientific and technical
      operation. Based on the experience gained at Maralinga, improved versions of this
      equipment were produced under contract for the People's Republic of China.

PMID- 15245850
TI  - Recent advances in aerial gamma-ray surveying.
AB  - Aerial gamma-ray surveying uses NaI(Tl) detectors mounted in small aircraft to
      measure gamma radiation, emitted from the earth's surface. The data are collected
      as gamma-ray spectra, typically with 1 s counting times, from which are derived
      K, U and Th concentrations in the ground. Applications of aerial surveying
      include geological mapping for mineral exploration, soil mapping for agriculture,
      pollution studies and location of lost sources. Recent advances in applying
      statistical methods to the spectral data have resulted in large reductions in the
      noise levels in the surveys. Some of the methods available to do this include
      noise adjusted singular value decomposition (NASVD) [Proceedings of Exploration
      97: Fourth Decennial International Conference on Mineral Exploration (1997) 753]
      and maximum noise fraction (MNF) and enhanced MNF (eMNF) [Explor. Geophys. 31
      (2000) 73]. These methods, in general, apply normalization for variance to the
      spectra, use a principal component method to obtain the "significant" components
      of the data and reconstruct cleaned spectra, which are then processed in a
      standard manner to get radionuclide concentrations. However, they differ in the
      detail of the application and thus give slightly different results. In this
      paper, the application of noise reduction methods to various synthetic surveys is
      used to examine the strengths and weaknesses of the methods. In tests where there
      are high correlations between U and Th, the eMNF method performs best although
      the results are improved by prior clustering of the data by the Th/U ratio. If
      the data show no correlations, then the effectiveness of all the noise removal
      methods is reduced. If a data set is small (<1500 spectra), then MNF appears to
      be the better method. Consideration of the various tests suggests an optimum
      process whereby spectra are sorted into groups by the Th/U ratio of areas
      identified in a standard processing and then cleaned by eMNF or MNF, depending on
      the number of spectra in each group.

PMID- 15245851
TI  - Radionuclide applications in laboratory studies of environmental surface
      reactions.
AB  - The advantages of using radionuclides for laboratory studies of environmental
      processes include the wide range of element concentrations that can be studied,
      the capability to simultaneously study several isotopes in a single experiment,
      the direct applicability to the behaviour of radioactive waste or fallout, and
      the ability to study the mechanisms, reversibility and kinetics of environmental
      reactions under controlled conditions. These attributes are demonstrated using
      specific examples drawn from case studies in Australia, including radionuclide
      fallout onto tropical soils, the association of trace metals with harbour
      sediments and the behaviour of uranium in natural and contaminated systems.

PMID- 15245852
TI  - Properties of two tropical soils in relation to the transport of radionuclides in
      the rhizosphere.
AB  - The uptake of radionuclides by commercial crops is being studied at two sites,
      Blain and Tippera, in a research farm in the Northern Territory, Australia.
      Studies have been performed to characterise the properties of the two soils,
      particularly the hydraulic properties that are considered to significantly
      influence the transport and plant uptake of these radionuclides in the soils The
      Blain soil, a sandy loam, has been categorised as SM according to the Unified
      Soil Classification System. Quartz is the dominant mineral for the Blain soil.
      The Tippera soil, a kaolinitic clayey loam has been categorised as CL. Chemical
      analysis results were consistent with these findings. The saturated hydraulic
      conductivity values were of the order of 10(-4) cm/s for the Blain soil. These
      values were greater by 3-4 orders of magnitude than those for the Tippera soils.
      The results obtained from the hydraulic property measurements were used to
      estimate the unsaturated hydraulic properties. A bimodal description based on van
      Genuchten-type partial saturation functions was used for the estimation. The
      estimation was qualitatively consistent with the soil types.

PMID- 15245853
TI  - Seasonal changes of redox potential and microbial activity in two agricultural
      soils of tropical Australia: some implications for soil-to-plant transfer of
      radionuclides.
AB  - Very little is known of the factors controlling soil-to-plant transfer of
      radionuclides in tropical environments. As part of an IAEA/FAO coordinated
      research project (CRP) designed to elucidate some of those factors, near-surface
      samples of two agricultural red-earth soils (Blain and Tippera) were collected
      from a study site in the Northern Territory. The climate is tropical monsoonal
      with crops being grown over the wet season from December to March/April. It is
      important to understand soil variables that may be related to this dramatic
      seasonality. In this investigation, soil redox state and microbial populations
      were assessed before and after the growing season with a view to generating
      hypotheses for future evaluation. The X-ray absorption near edge structure
      (XANES) technique was used to determine overall changes in the solid-state redox
      speciation of Fe and Mn in soils across the growing period. Fe speciation did not
      change but approximately 10% of the total Mn was oxidised from Mn(II) to Mn(III)
      and Mn(IV) in both soils between October 1999 and April 2000. An apparent
      disconnect between Fe and Mn was not unexpected given the >10 times higher
      concentration of Fe in the soils compared with Mn. These results have
      implications for the bioavailability of redox sensitive radionuclides such as Tc
      and Pu. Similarly, microbial population estimates were derived before and after
      the growing period. Total bacterial populations did not vary from 10(6) to 10(7)
      colonies per gram. Fungal populations increased over the growing season from 3-6
      x 10(5) to 1-4 x 10(6) colonies per gram of soil. Fungi have the potential to
      decrease soil pH and hence increase the bioavailability of radionuclides such as
      Cs. In addition, fungi act to facilitate plant nutrition. This could lead to
      enhanced accumulation of nutrient analogues (e.g. Sr and Ra for Ca; Tc for Mn),
      but this effect may be masked by improved biomass production.

PMID- 15245854
TI  - 'Performance of understanding': a new model for assessment?

PMID- 15245855
TI  - Modularisation - flexible or restrictive professional education.
AB  - In response to the Dearing Report [Higher education in the learning society.
      Report of the National Committee of Inquiry into Higher Education. HMSO, London,
      1997] modularising courses has been a major activity in schools of nursing and
      midwifery. This should make it easier for students to transfer between courses,
      university to university with credit for academic achievement. In respect of
      mental health nursing students the effect upon opportunities for personal and
      professional development is considered. The paper questions whether a modular
      framework of learning experiences meaningfully prepares students for their future
      as mental health nurses. The continued use of an adapted [A. Beattie, in: P.
      Allan, M. Jolley (Eds.), The Curriculum in Nurse Education, Croom Helm, London,
      1997] fourfold curriculum model in working with students is contrasted with the
      process of modularisation. Challenges that have arisen for mental health nursing
      lecturers to continue with this are discussed.

PMID- 15245856
TI  - Remembrance of things past: the utilisation of context dependant and
      autobiographical recall as means of enhancing reflection on action in nursing.
AB  - Reflection on action is widely accepted as a means of developing an individual's
      experience and professional and scientific knowledge [Accident and Emergency
      Nursing 4 (1996) 135]. Reflection can occur when a nursing event is examined and
      explored which may lead to the individual acquiring new perspectives and new
      knowledge regarding the event. This paper contends that the exploration of an
      event in practice can be better understood if viewed in the context of previous
      similar experiences. A five stage structured process is suggested whereby the
      nurse intentionally returns to former places and recreates previously experienced
      affective states with the purpose of accessing context and state dependent
      memories. These rediscovered remembrances can then serve as the raw material for
      reflection on nursing problems and dilemmas. A comparison of the current problem
      with the past experience may lead to new learning and a deepening of the
      reflective process. The seminal work of Marcel Proust is referred to in order to
      illustrate the process and examples from practice are also identified.

PMID- 15245857
TI  - An empirically-derived clinical placement evaluation tool: a 3-country study.
AB  - We report the development of a brief and simple-to-complete clinical placement
      evaluation scale. Unlike many previous attempts to develop such tools, the one
      reported here gives reliable numerical scores with a firm empirical foundation.
      The scoring correlates well between three European countries: UK, Finland, and
      Germany.

PMID- 15245858
TI  - Empowerment and assessment: a dichotomy?
AB  - Institutions of higher education are sites where the rhetoric of learning
      increasingly collides with the diverse needs of both learners and educators.
      Demands on tertiary institutions from the workplace, students themselves and the
      increasing demand for skilled graduates in the face of diminishing resources
      strongly suggest that intelligent and creative approaches to learning play a
      pivotal role in the success of higher education. Throughout tertiary education
      the subject of assessment is central to the complex processes involved in student
      learning. Therefore, it is important that nursing academics and practitioners
      involved in assessing student learning develop insight and awareness of the
      theories and philosophies that underpin different assessment strategies. This
      will inform teaching and learning practice to the benefit of all stakeholders.
      This paper examines issues of assessment in higher education; it will locate and
      deconstruct some principles underpinning traditional and innovative methods
      associated with assessment and suggest that creative approaches that embrace
      adult learning principles will empower students and ultimately facilitate more
      effective learning.

PMID- 15245859
TI  - The questioning skills of tutors and students in a context based baccalaureate
      nursing program.
AB  - This paper explores, describes and compares the types and levels of questions
      asked by 30 randomly selected tutors (nurse educators) and their 314 students in
      context-based learning tutorial seminars in a Canadian baccalaureate nursing
      program. Thirty 90-min seminars were audio taped, transcribed and coded using a
      Questioning Framework designed for this study. The framework includes types and
      levels of questions, related wording and examples. The results of this study
      indicate that the majority of questions asked by tutors and students in the first
      three years of the program were framed at the low level (knowledge,
      comprehension, and application) and were aimed at seeking yes/no responses and
      factual information more so than probing. Although these questions are important
      to facilitate the teaching/learning process, educators and students need to
      increase the number of questions requiring analysis, synthesis, and evaluation as
      well as questions that involve probing, exploration, and explanation - questions
      believed to activate and facilitate critical thinking skills. Recommendations
      include the need for students and tutors to be taught how to question, the
      creation of a supportive environment for questioning and the use of appropriate
      strategies to teach the use of higher order questions. Future research using a
      cross sectional longitudinal design and qualitative approaches are also
      recommended. This study has direct implications for enhancing student learning
      and the development of nurse educators.

PMID- 15245860
TI  - A comparative study of the course-related family and financial problems of mature
      nursing students in Scotland and Australia.
AB  - This study reports a comparative survey of mature students undertaking pre
      registration undergraduate nursing education in Australia and Scotland. The study
      aimed to explore comparisons between the course-related and course-related
      financial difficulties faced by mature students in two very different educational
      and funding systems. Financial stress is a predictor of both physical and mental
      health problems. A similar pattern of course-related problems were reported by
      both Australian and Scottish students with the exception that Scottish students
      experienced more problems with childcare and caring for elderly relatives. Course
      related problems may be inherent in the nature of undergraduate nursing education
      although the relatively time-intensive nature of Scottish curricula may explain
      the childcare and elderly relatives difference. Scottish students reported higher
      overall financial-related problems but Australian students reported more problems
      with funding placements. These findings have implications for both curriculum
      designers and policy makers.

PMID- 15245861
TI  - Student impressions of clinical nursing.
AB  - Informal verbal reports of attitudes of nursing degree students over two years
      suggested a growing trend of lack of motivation in pursuing a career in nursing
      upon qualification. In an attempt to discover the reasons for this a small
      qualitative study was undertaken. Fourteen undergraduate nursing students from
      years 3 and 4 from a BSc Nursing Sciences (Hons) program were sampled using a
      volunteer sampling method. The degree program is one of two pre-registration
      programs, the other being the Diploma course. Audio-taping was used to record the
      responses of students in two focus groups convened for the purpose of this study.
      Three main themes: ward culture; mentors; and learning from the negative reflect
      the students' accounts of the influence of their clinical experiences on their
      motivation for a nursing career. Students indicated that their interest in
      nursing as a career was directly affected by their observations of trained nurses
      and the nurses' attitudes toward them as students.

PMID- 15245862
TI  - Portfolio assessment: practice teachers' early experience.
AB  - Experience was recognised to be a vital source of learning as long ago as 1762
      [Emile, Everyman, London, 1993] and reflection on practice experience may be one
      way forward in addressing nursing's anxieties concerning the practice theory gap.
      However, despite the acceptance that subjectivity in the process seems inevitable
      and potentially important, little is understood of the practitioner's experience
      of practice assessment. Two questionnaires sought the views of specialist
      community nursing practitioner (SCNP) programme (United Kingdom Central Council
      for Nursing, Midwifery and Health Visiting (UKCC) 2001) practice teachers (PTs)
      on the introduction of the portfolio approach to practice assessment. These were
      distributed to 62 and 76 PTs and the response rates were 32% and 50%,
      respectively. Responses of those PTs from the three specialisms participating in
      the piloting of the portfolio approach were compared with those using an existing
      approach. An action research method was adopted which attempted to use
      established theory to explain the challenges presented by the introduction of
      this approach and ultimately to raise the PT group's awareness of assessment
      issues. Both qualitative and quantitative data were collected and the findings
      support the use of the portfolio approach to practice assessment. The PT
      experience of portfolio use was found to be a largely positive one. PTs reported
      the utility of the portfolio in prompting student self-evaluation of learning.
      Concerns were expressed by PTs around the quality of portfolio evidence although
      many felt that it had promoted students' reflection on practice. Inter-PT
      reliability in practice assessment was identified as a topic for PT continuing
      professional development. Many sources of evidence, including patient feedback,
      were used by PTs in their assessment of students although PTs using the portfolio
      approach used less first-hand experience of students' practice in their
      assessments of competence, relying more on written evidence, than those PTs using
      a traditional approach to practice assessment.

PMID- 15245863
TI  - The workforce in health and social care services to older people: developing an
      education and training strategy.
AB  - Planning workforce development across the health and social care services for
      older people presents a formidable challenge. In England, Workforce Development
      Confederations are responsible for commissioning the education and training of
      the current and future health and social care workforce. This article reports on
      an analysis of local issues in planning the workforce for older people's services
      undertaken in one Confederation. It reports on the perceived priorities for
      developing the workforce in older peoples services in a policy environment where
      multiple initiatives were competing for attention. It highlights the key
      challenges in planning a strategy that embraces numerous service and education
      providers and offers practical solutions. Although this analysis was in one
      Confederation, the issues raised have relevance for other Confederations and
      their education and service partner organisations.

PMID- 15245864
TI  - In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination
      with isoniazid, against Mycobacterium tuberculosis.
AB  - The antimicrobial peptide protegrin-1 (PG-1) inhibited the growth in vitro of
      drug-susceptible and multidrug-resistant Mycobacterium tuberculosis; a lower
      activity was shown by human beta-defensin-1 (HBD-1) against both strains. The
      combination of PG-1 or HBD-1 with isoniazid significantly reduced M. tuberculosis
      growth in comparison with the peptides or isoniazid alone.

PMID- 15245865
TI  - Parabutoporin--an antibiotic peptide from scorpion venom--can both induce
      activation and inhibition of granulocyte cell functions.
AB  - Parabutoporin (PP) affects motility and NADPH oxidase activity in normal human
      polymorphonuclear neutrophils and in granulocytic HL-60 cells. These PP-induced
      interactions utilize a Rac activation pathway. PP induces chemotaxis of
      neutrophils and HL-60 cells via a pertussis toxin-sensitive way, thus using
      trimeric G-proteins. The enhanced chemotaxis is also apparent in undifferentiated
      HL-60 cells which lack functional formyl peptide receptors. On the other hand, PP
      strongly reduces the superoxide production by the NADPH oxidase complex after
      either PMA or fMLP activation of granulocytes. These combined results strongly
      suggest a direct activation of G-proteins and subsequent Rac activation as the
      basis for the observed effects. The unexpected inhibitory effect of PP, despite
      Rac activation, on superoxide production in granulocytes is explained by the
      direct interaction of membrane localized PP which prevents the formation of a
      functional NADPH oxidase complex.

PMID- 15245866
TI  - Identification of five new bradykinin potentiating peptides (BPPs) from Bothrops
      jararaca crude venom by using electrospray ionization tandem mass spectrometry
      after a two-step liquid chromatography.
AB  - Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were
      described in the middle of 1960s and were the first natural inhibitors of the
      angiotensin-converting enzyme displaying strong anti-hypertensive effects in
      human subjects. The BPPs can be recognized by their typical pyroglutamyl proline
      rich oligopeptide sequences presenting invariably a proline residue at the C
      terminus. In the present study, we identified 18 BPPs, most of them already
      described for the B. jararaca venom. We isolated and sequenced new peptides
      ranging from 5 to 14 amino acid residues exhibiting similar amino acid sequence
      features. The applied methodology consisted of a strait two-step liquid
      chromatography, followed by mass spectrometry analysis. Besides the amino acid
      sequence homology, the corresponding synthetic peptides were able to potentiate
      bradykinin on the isolated guinea-pig ileum.

PMID- 15245867
TI  - Actinchinin, a novel antifungal protein from the gold kiwi fruit.
AB  - An antifungal protein designated actinchinin, with an N-terminal sequence
      different from that of the thaumatin-like antifungal protein from green kiwi
      fruit, was isolated from the gold kiwi fruit. The antifungal protein, unlike its
      counterpart from green kiwi fruit, did not exert antifungal activity against
      Botrytis cinerea, but was active against Fusarium oxysporum which was
      unresponsive to thaumatin-like protein from green kiwi fruit. Actinchinin was
      isolated using a protocol that comprised ion exchange chromatography on CM
      cellulose, affinity chromatography on Affi-gel blue gel, ion exchange
      chromatography by fast protein liquid chromatography (FPLC) on Mono S, and gel
      filtration by FPLC on Superdex 75. Actinchinin was adsorbed on CM-cellulose, Affi
      gel blue gel and Mono S. It was devoid of mitogenic activity toward mouse
      splenocytes. In contrast to thaumatin-like protein from green kiwi fruit,
      actinchinin lacked HIV-1 reverse transcriptase inhibiting activity.

PMID- 15245868
TI  - Identification of a cDNA encoding DH, PBAN and other FXPRL neuropeptides from the
      tobacco hornworm, Manduca sexta, and expression associated with pupal diapause.
AB  - We have cloned the diapause hormone (DH)-pheromone biosynthesis activating
      neuropeptide (PBAN) cDNA from the suboesophageal ganglion (SG) of Manduca sexta
      pupae using rapid amplification of cDNA ends. The Mas-DH-PBAN cDNA encodes a
      preprohormone of 194 amino acids that contains five peptides (PBAN, DH-like, and
      alpha-, beta-, gamma-SGNP), all of which share a common FXPRL sequence at the C
      terminus. Yet, the sequences are rather distinct from those reported from other
      species: Mas-alpha-SGNP has a unique C-terminal FXPEL (the arginine or lysine at
      FXPR(or K)L is replaced by glutamic acid), Mas-gamma-SGNP is one amino acid
      shorter than its counterpart in other species, and Mas-PBAN contains two extra
      residues not seen in other species. Mas-DH-like peptide has the highest homology
      (83%) to Bombyx mori DH. Northern blot analysis shows a single mRNA corresponding
      in size to the Mas-DH-PBAN cDNA detected in brain-SG samples of pupae and adults,
      suggesting that these peptides are derived from a precursor through
      posttranslational processing. Using the more sensitive method of RT-PCR, DH-PBAN
      mRNA is also detectable in thoracic ganglia, although the expression is much
      lower than in the SG. Developmental profiles of DH-PBAN transcripts in the early
      pupal stage reveal different patterns in diapause and nondiapause individuals.
      While a conspicuous drop in expression of the DH-PBAN gene is noted in diapausing
      pupae 9 days after pupation, high expression persists in nondiapausing
      individuals. At earlier stages (wandering larva and day 3 pupae) expression is
      high in diapausing individuals but low in nondiapausing individuals. These
      observations suggest a possible contribution of the DH-like peptide to the
      induction phase of diapause in M. sexta.

PMID- 15245870
TI  - Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human
      coronary artery smooth muscle cells.
AB  - We examined the effects of tumor necrosis factor (TNF)-alpha on the expression
      and functionality of adrenomedullin (AM) receptors in cultured human coronary
      artery smooth muscle cells. Analysis of real-time quantitative polymerase chain
      reactions showed that these cells abundantly express two AM receptors comprised
      of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying
      protein 1 (RAMP1) or RAMP2. TNF-alpha induced time- and dose-dependent decreases
      in the expression of CRLR and RAMP1/2 mRNAs, thereby diminishing AM-evoked cAMP
      production. The suppression of these three mRNAs was unaffected by inhibiting
      NOS, protein kinase G, protein kinase A, superoxide formation or NF-kappaB
      activation.

PMID- 15245869
TI  - Differential gene expression of adrenomedullin receptors in pressure- and volume
      overloaded heart--role of angiotensin II.
AB  - Left ventricular (LV) adrenomedullin (AM) gene expression differs between
      pressure overload (POL) and volume overload (VOL) and angiotensin II could be a
      critical stimulator of AM gene expression in POL and VOL models. Calcitonin
      receptor-like receptor (CRLR) co-expressed with receptor activity modifying
      protein 2 (RAMP2) or RAMP3 functions as an AM receptor. Levels of CRLR, RAMP2 and
      RAMP3 mRNA that were significantly increased within 24 h returned to the basal
      level at 5 days after the imposition of POL in the present study. In contrast,
      mRNA levels of CRLR and RAMP2 gradually increased over 6 weeks after the
      imposition of VOL. Continuous infusion of angiotensin II stimulated LV AM gene
      and AM receptor gene expression independently of LV peak-systolic and LV end
      diastolic pressure. The gene expression of LV AM receptors increased in different
      types of cardiac overload. The present study revealed an intimate association
      between the AM signaling system and angiotensin II.

PMID- 15245871
TI  - The design of antagonist peptide of hIL-6 based on the binding epitope of hIL-6
      by computer-aided molecular modeling.
AB  - The interaction between human interleukin-6 (hIL-6) and human interleukin-6
      receptor (hIL-6R) is the initial and most specific step in the hIL-6 signaling
      pathway. Understanding its binding core and interaction mechanism at amino acid
      level is the basis for designing small IL-6 inhibiting molecules, such as
      peptides or lead compounds. With Docking method, the complex structure composed
      of hIL-6 and its alpha-subunit receptor (hIL-6R) was analyzed theoretically. By
      using structure-based analysis and phage display methods, the loop AB (from Lys67
      to Glu81) of hIL-6 was found to be the important binding epitope of hIL-6R. By
      means of computer-aided design, the mimic antagonist peptide (14 residues) was
      designed and synthesized. Using multiple myeloma cell line (XG7), IL-6 dependent
      cell line, as test model, the influence of antagonist peptides on the
      proliferation of XG7 cells was investigated. The results showed that the
      synthetic peptide could be competitive to bind to hIL-6R with hIL-6, and the
      effect was concentration dependent. The theoretical design approach is a powerful
      alternative to phage peptide library for protein mimics. Such mini-peptide is
      more amenable to synthetic chemistry and thus may be useful starting points for
      the design of small organic mimics.

PMID- 15245872
TI  - Endothelin 1 and 3 enhance neuronal nitric oxide synthase activity through ETB
      receptors involving multiple signaling pathways in the rat anterior hypothalamus.
AB  - We have previously reported that endothelin 1 and 3 (ET-1, ET-3) through the ETB
      receptor decrease norepinephrine release in the anterior hypothalamus and
      activate the nitric oxide (NO) pathway. In the present work we sought to
      establish the receptors and intracellular mechanisms underlying the increase in
      nitric oxide synthase (NOS) activity stimulated by ET-1 and ET-3 in the rat
      anterior hypothalamus. Results showed that ETs-stimulated NOS activity was
      inhibited by a selective ETB antagonist (BQ-788), but not by a selective ETA
      antagonist (BQ-610). In addition, NOS activity was not altered in the presence of
      an ETA agonist (sarafotoxin 6b), but it was enhanced in the presence of a ETB
      agonist (IRL-1620). Both Nomega-nitro-L-arginine methyl ester (NOS inhibitor),
      and 7-nitroindazole (neuronal NOS inhibitor) diminished ETs-stimulated NOS
      activity. The stimulatory effect of ETs on NOS activity was inhibited in the
      presence of PLC, PKC, PKA and CaMK-II inhibitors (U-73122, GF-109203X, H-89 and
      KN-62, respectively), and the IP3 receptor selective antagonist, 2-APB. Our
      results showed that both ET-1 and ET-3 modulate neuronal NOS activity through the
      ETB receptor in the rat anterior hypothalamus involving the participation of the
      PLC-PKC/IP3 pathway as well as PKA and CaMK-II.

PMID- 15245873
TI  - Facilitative effect of a novel AVP fragment analog, NC-1900, on memory retention
      and recall in mice.
AB  - In order to determine the mechanism of action of a new AVP(4-9) analog, NC-1900,
      on memory processes, memory retention and retrieval tests were conducted in a
      step-through passive avoidance (PA) task in mice. The administration of NC-1900
      facilitated memory retention and retrieval in the PA task through vasopressin1A
      (V1A) receptors but not V2 receptors. The effect of NC-1900 on memory retention
      test performance appeared to be due to activation of the protein kinase C (PKC)
      signaling pathway via V1A receptors; however, the modulation of PKC was not
      essential for the facilitative effect of the new peptide in the retrieval test.
      The facilitation of memory retrieval by NC-1900 may also be mediated by other non
      PKC-dependent signaling pathways, such as the phospholipase C-inositol
      trisphosphate pathway.

PMID- 15245874
TI  - Effects of peptide YY(3-36) on PRL secretion: pituitary and extra-pituitary
      actions in the rat.
AB  - Polypeptide YY(3-36) (PYY(3-36)) is a gastrointestinal secreted molecule, agonist
      of neuropeptide Y (NPY) receptor subtypes Y2 and Y5, that has been recently
      involved as anorexigenic signal in the network controlling food intake. Notably,
      several factors primarily involved in food intake control and energy homeostasis
      (as leptin, orexins, ghrelin and NPY) have been linked also to the regulation of
      anterior pituitary hormone secretion and carry out pleiotropic effects upon the
      reproductive axis. However, whether similar actions are conducted by PYY(3-36)
      remains so far largely unexplored. Present studies were undertaken to analyze the
      potential effects of PYY(3-36) in the control of prolactin (PRL) secretion in the
      rat. To this end, responses to PYY(3-36) in terms of PRL secretion were monitored
      in vitro, after pituitary exposure to 10(-8) to 10(-6) M concentrations, and in
      vivo, after i.p. administration of different doses of PYY(3-36) (3, 10 and 30
      microg/kg) to prepubertal male and female rats. In addition, the in vivo effects
      of PYY(3-36) were tested after central (i.c.v.) administration of 3 nmol of the
      peptide to prepubertal rats, and in hyperprolactinaemic aged females. PYY(3-36)
      stimulated, in a dose-dependent manner, in vitro PRL secretion by pituitaries
      from prepubertal male and female rats. In contrast, systemic administration of
      PYY(3-36) failed to modify serum PRL levels, whereas central infusion of PYY(3
      36) significantly inhibited PRL secretion in prepubertal rats. Finally, PRL
      secretion was stimulated in aged hyperprolactinaemic female rats by systemic
      administration of PYY(3-36). In conclusion, the anorexigenic peptide PYY(3-36)
      may participate in the control of PRL secretion in the prepubertal rat, acting at
      pituitary (stimulatory effect) and extra-pituitary (likely inhibitory action at
      the hypothalamus) sites of the lactotrope axis. Moreover, net actions of PYY(3
      36) on PRL secretion may depend on the age and prevailing PRL levels.

PMID- 15245875
TI  - Daily variation in the concentration of neuropeptide Y in the rat atrium: effects
      of age and photoperiodic conditions.
AB  - This study investigates the release characteristics of neuropeptide Y (NPY) from
      young (10 weeks) and old (22 months) rat atrium. Levels of NPY release from
      samples of atrium were studied by organ perifusion. Rats were exposed to
      light:dark (LD) cycles of 12:12 or 18:6 and sacrificed at different circadian
      stages: 0, 4, 7, 12, 18, and 20 h after dark onset (HADO) for LD 12:12 or 0, 2,
      3.5, 6, 15, and 22 HADO for LD 18:6. The heart was collected, and the right
      atrium was removed, weighed, and perifused with Krebs-bicarbonate buffer for 100
      min, including a period of 50 min for stabilization of secretion rate. NPY
      concentrations released by atrium did not differ between the two age groups. NPY
      exhibited daily variations in concentrations in LD 12:12, with a peak during the
      end of scotophase, at 12 HADO, in both the young and old rats. These variations
      were strongly modified in LD 18:6, where the pattern of the release exhibited two
      peaks occurring during the two thirds of dark (3.5 HADO) and light (22 HADO)
      periods. This strongly suggests that the NPY rhythm is dependent on the
      environmental light:dark cycle. In this paper we show that NPY concentrations in
      the rat atrium exhibit daily variations, which are maintained with ageing.
      Moreover, photoperiod greatly influences NPY levels in the atrium.

PMID- 15245876
TI  - The effect of neurotensin on insulin-induced proliferation of human fibroblasts.
AB  - Neurotensin has been shown to influence growth in a number of cancerous and non
      cancerous cells and to enhance the proliferative effects of growth factors
      without itself inducing proliferation. Here we show that neurotensin potentiates
      the proliferative effects of insulin on IMR90 human fibroblasts in a
      concentration and neurotensin receptor type 1-dependent manner. This potentiating
      effect of neurotensin was blocked by inhibitors of phospholipase C and protein
      kinase C, was accompanied by an increase in the level of soluble inositol
      phosphates and did not involve an autocrine factor. These results show that
      neurotensin can enhance insulin-dependent proliferation of human fibroblasts and
      suggest a possible role for neurotensin in tissue growth and repair.

PMID- 15245877
TI  - Cloning and characterization of the glucagon receptor from cynomologous monkey.
AB  - The glucagon receptor was cloned from cynolomologous monkey. A frame-shift
      mutation at the 3' end of the monkey transcript results in a C-terminal extension
      of 14 amino acids. This extension is not observed in either the human or rodent
      glucagon receptors. Monkey glucagon receptor was expressed in CHO cells, either
      with (mkGCGR) or without (mkGCGRDelta14) the 14-amino acid C-terminal extension
      to approximate the human receptor. Both forms of the monkey receptor bound
      glucagon with similar affinity and showed glucagon-stimulated cAMP production,
      however the full-length form of the monkey receptor (mkGCGR) was less sensitive
      to glucagon in its ability to stimulate cAMP than the shortened form
      (mkGCGRDelta14). PCR of genomic DNA from baboon and rhesus monkeys suggests that
      they express a form of the receptor similar to that of cynomologous monkey, while
      in chimpanzee, the receptor is similar to the human form.

PMID- 15245878
TI  - Effects of centrally injected GLP-1 in various experimental models of gastric
      mucosal damage.
AB  - Glucagon-like peptide-1 (GLP-1) is accepted to be a peptide involved in the
      central regulation of gastrointestinal function, but its potential
      gastroprotective effect is not clear. The aim of this study was to investigate
      whether intracerebroventricularly injected GLP-1 has protective effects on
      gastric mucosal lesions induced by several models, and if yes, whether these
      effects are due to the gastric antisecretory effect of the peptide. GLP-1 which
      was injected in three different doses (1, 10, 100 ng/10 microl; i.c.v.) to
      conscious rats prevented the mucosal lesions induced by reserpine and ethanol,
      but did not prevent the gastric mucosal lesions induced by pyloric ligation. In
      addition, 1 ng/10 microl dose of centrally injected GLP-1 inhibited gastric acid
      secretion in pylorus-ligated rats. As a result, we conclude that
      intracerebroventricularly injected GLP-1 may play a role in the prevention of
      gastric mucosal lesions induced by certain experimental models and this
      gastroprotective effect may be independent from its antisecretory effect.

PMID- 15245879
TI  - Exogeneous and endogenous CCK inhibit ethanol ingestion in Sardinian alcohol
      preferring rats.
AB  - Ethanol ingestion, like food ingestion, stimulates release of the signaling
      molecule cholecystokinin (CCK) from the small intestine. Here, we investigated
      the possibility that ethanol-induced CCK release might be a negative-feedback
      control of ethanol ingestion, similar to its function as part of the mechanism by
      which ingested food produces meal-ending satiation. We used Sardinian alcohol
      preferring (sP) and Marchesian Sardinian (msP) alcohol-preferring rats, two
      apparently identical substrains that spontaneously ingest pharmacologically
      relevant amounts of ethanol, as well as their background strain, Wistar (W) rats.
      We demonstrated that: (1) intraperitoneal (IP), but not intracerebroventricular,
      injections of 0.5-4 microg/kg CCK-8 produced transient, dose-related reductions
      in 10% ethanol ingestion; (2) this inhibitory effect of CCK-8 on ethanol intake
      appeared behaviorally similar to its inhibitory action on ingestion of sucrose
      solutions; (3) the inhibitory effect of IP CCK-8 on ethanol ingestion occurred
      without evidence of tolerance when tests were repeated on consecutive days; (4)
      IP CCK-8 reduced ethanol intake despite simultaneously reducing blood ethanol
      levels (BALs); and (5) antagonism of CCK1 receptors with devazepide increased
      ethanol intake, indicating that endogenous CCK normally limits the size of bouts
      of ethanol ingestion. These results implicate peripheral CCK in the control of
      ethanol ingestion in sP and msP alcohol-preferring rats.

PMID- 15245880
TI  - Involvement of D1 dopamine receptors in the cognitive effects of angiotensin IV
      and des-Phe6 angiotensin IV.
AB  - An important role for angiotensin IV (Ang IV) in the processes of learning and
      memory has now been well established. We have previously found that
      intracerebroventricular (ICV) administration of Ang IV as well as des-Phe6-Ang IV
      enhances learning of conditioned avoidance responses (CARs), facilitates recall
      of a passive avoidance (PA) task, and improves object recognition (OR) in rats.
      Since the dopaminergic system is crucial for the cognitive processes, in this
      study our aim was to determine the dopaminergic D1 mediation of these effects
      using SCH 23390 as a selective D1 receptor antagonist. Male Wistar rats (180-200
      g), pretreated with SCH 23390 (R-[+]-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine) 0.05 mg/kg intraperitoneally (IP), were given Ang IV
      or des-Phe6-Ang IV (1 nmol ICV) 1 h later and then tested in the above cognitive
      paradigms, as well as in the open field and an elevated 'plus' maze to control
      for the unspecific, respectively, motor and emotional, effects of our treatments.
      Both, Ang IV and des-Phe6-Ang IV effectively enhanced learning of CARs (P <
      0.05), recall of PA (P < 0.001), and improved OR (P < 0.001). Pretreatment with
      SCH 23390 abolished the cognitive effects of both peptides. SCH 23390, Ang IV,
      and des-Phe6-Ang IV, given at the same doses and routes as in the cognitive
      tests, did not significantly influence crossings, rearings and bar approaches in
      the open field, nor the parameters measured in the elevated 'plus' maze, thus
      making a major contribution of the unspecific effects of our treatments to the
      results of the memory tests improbable. In conclusion, these results indicate
      that the functional dopaminergic D1 receptors are necessary for the Ang IV and
      des-Phe6-Ang IV cognitive effects to occur.

PMID- 15245881
TI  - Role of substance P in hypersensitivity reactions induced by paclitaxel, an
      anticancer agent.
AB  - The role of substance P in adverse pulmonary reactions induced by an anticancer
      agent paclitaxel was investigated in rats and humans who undertook post-operative
      chemotherapy for ovarian cancer. In rats, paclitaxel caused a marked plasma
      extravasation and edema in lungs with a concomitant decrease in arterial partial
      oxygen pressure, which were reversed by an NK1 antagonist LY303870. Substance P
      level in rat plasma and bronchoalveolar lavage fluid increased after paclitaxel
      injection. In 13 patients, plasma level of substance P but not histamine
      significantly (P < 0.05) increased during paclitaxel infusion. Therefore,
      substance P rather than histamine may be involved in paclitaxel hypersensitivity.

PMID- 15245882
TI  - Antifungal peptides, a heat shock protein-like peptide, and a serine-threonine
      kinase-like protein from Ceylon spinach seeds.
AB  - Two antifungal peptides (designated alpha- and beta-basrubrins) with molecular
      masses of 4-5 kDa and distinct N-terminal sequences, and a peptide and a protein
      with N-terminal sequences resembling heat shock protein (hsp) and serine
      threonine kinase, respectively, were isolated from seeds of the Ceylon spinach
      Basella rubra. The purification procedure entailed saline extraction, (NH4)2SO4
      precipitation, ion exchange chromatography on DEAE-cellulose, affinity
      chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose,
      and FPLC-gel filtration on a Superdex peptide column. alpha- and beta-basrubrins
      inhibited mycelial growth in Botrytis cirerea with an IC50 value of 7.5 and 14.7
      microM, respectively, Mycosphaerella arachidicola with an IC50 of 12.4 and 6.9
      microM, and Fusarium oxysporum with an IC50 of 5.8 and 6.2 microM. Neither alpha
      basrubrin nor beta-basrubin exhibited DNase, RNase, lectin or protease activity,
      indicating that their antifungal action is not due to these activities. HIV-1
      reverse transcriptase was inhibited by alpha- and beta-basrubrins with an IC50 of
      246 and 370 microM, respectively. Translation in rabbit reticulocyte lysate was
      inhibited by alpha- and beta-basrubrins with an IC50 of 400 and 100 nM. The heat
      shock protein-like peptide and serine-threonine kinase-like protein exhibited a
      molecular mass of 3 and 30 kDa, respectively. They inhibited neither translation
      in a rabbit reticulocyte system at concentrations up to 50 microM nor HIV-1
      reverse transcriptase activity at concentrations up to 400 microM. They did not
      exert antifungal activity toward B. cinerea, M. arachidicola, and F. oxysporum
      when tested up to 16 microg. None of the aforementioned proteins demonstrated
      DNase, RNase, protease or lectin activity.

PMID- 15245884
TI  - pH-sensitive microsphere delivery increases oral bioavailability of calcitonin.
AB  - Oral calcitonin (CT) administration is aimed in the treatment of calcemia in
      order to circumvent the required regular injections. CT containing microspheres
      (MS) were designed for colonic delivery by applying a pH-sensitive polymer
      Eudragit P-4135F for a double emulsion [water/oil/water (w/o/w)] microsphere
      preparation technique. CT was incorporated in the internal aqueous phase and
      carboxyfluorescein was encapsulated similarly to allow the characterization of
      the MS dissolution behavior. Eudragit P-4135F was found to keep the leakage of CT
      and carboxyfluorescein in vitro at pH 6.8 below 20% within 4 h while at pH 7.4, a
      fast release was observed for both, dye and peptide. Plasma levels of
      carboxyfluorescein after oral MS administration proved a sustained release in a
      rat model, where Cmax of carboxyfluorescein solution was found at around 60 min
      while for MS formulations it was detected after 4 h. At a dose of 20 microg
      CT/kg, no significant calcemic effects were found by MS formulations. However,
      increasing the dose to 100 microg CT/kg resulted in a distinct calcemia and
      revealed the sustained release properties of the MS. The relative pharmacological
      effect became most intense after 8-12 h based on the selective pH-dependent
      delivery. MS showed a fourfold increase of the area above the curve of calcium
      blood level compared to levels reached after CT solution. The coencapsulation of
      chitosan in the MS as absorption enhancer did not show any additional effect. The
      MS formulations proved their applicability as a promising device for pH-dependent
      colonic CT delivery and might be useful for other peptides.

PMID- 15245883
TI  - Antifungal proteins and peptides of leguminous and non-leguminous origins.
AB  - Antifungal proteins and peptides, as their names imply, serve a protective
      function against fungal invasion. They are produced by a multitude of organisms
      including leguminous flowering plants, non-leguminous flowering plants,
      gymnosperms, fungi, bacteria, insects and mammals. The intent of the present
      review is to focus on the structural and functional characteristics of
      leguminous, as well as non-leguminous, antifungal proteins and peptides. A
      spectacular diversity of amino acid sequences has been reported. Some of the
      antifungal proteins and peptides are classified, based on their structures and/or
      functions, into groups including chitinases, glucanases, thaumatin-like proteins,
      thionins, and cyclophilin-like proteins. Some of the well-known proteins such as
      lectins, ribosome inactivating proteins, ribonucleases, deoxyribonucleases,
      peroxidases, and protease inhibitors exhibit antifungal activity. Different
      antifungal proteins may demonstrate different fungal specificities. The
      mechanisms of antifungal action of only some antifungal proteins including
      thaumatin-like proteins and chitinases have been elucidated.

PMID- 15245885
TI  - Characterization and in vitro degradation of poly(2,3-(1,4-diethyl tartrate)-co
      2,3-isopropyliden tartrate).
AB  - In the present study, a less known polyester based on tartaric acid was
      characterized with respect to its degradation mechanism. Poly(2,3-(1,4-diethyl
      tartrate)-co-2,3-isopropyliden tartrate) (PTA) differs from commonly used
      biodegradable polyesters, such as poly(lactides-co-glycolides) (PLGA) by the
      presence of additional cleavable bonds in the polymer side chains. This
      modification results in different polymer properties and influences polymer
      degradation. The hydrolytic degradation of PTA was studied in parallel to PLGA
      using disc-shape matrices, which were obtained by compression-molding. The discs
      were incubated in pH 7.4 phosphate buffer solution at 37 degrees C. The degraded
      samples were characterized for percentage mass loss, water absorption, decay of
      molecular weight and change in glass transition temperature. The results
      demonstrate that the degradation of PTA proceeds via bulk erosion similar to
      PLGA. However, the degradation of PTA implants is characterized by a rapid mass
      loss within a short period of time appearing after a definite lag phase without
      remarkable mass loss. This makes the polymer promising for pulsatile drug release
      systems.

PMID- 15245886
TI  - In vitro transdermal iontophoretic delivery of leuprolide under constant current
      application.
AB  - Transdermal delivery of Leuprolide, a nonapeptide LHRH agonist, was studied using
      constant current iontophoresis to explore methods for improving iontophoretic
      efficiency and determine the feasibility of delivery of therapeutic doses of the
      drug. Universal buffer consisting of citrate, phosphate and borate was used to
      carry out in vitro permeation experiments with heat separated human epidermis at
      pH 4.5 and 7.2. In addition, the effect of substituting this buffer with a
      macromolecular electrolyte, polymaleic acid, on the drug flux and the
      transference number was studied. Current densities from 0.5 to 2.3 microA/cm2
      were used requiring moderate potential differences between 60 and 420 mV to be
      applied thus limiting irreversible epidermal membrane alterations. The rather
      high electrical resistance of the epidermis of the order of 200 kohms cm2 was
      related to the sub-physiological electrolyte concentration. Resistance was
      continuously monitored to guarantee barrier integrity of the membrane. The
      permeation rate increased linearly with the current density for the universal
      buffer and was at pH 7.2 almost double that at pH 4.5 despite the greater ionic
      valence of the drug at pH 4.5 compared to pH 7.2; this being because of the
      opposite direction of the electroosmotic flow at the two pH values. Drug
      transference number at both pH values was approximately 0.5%. Replacement of the
      universal buffer with polymaleic acid yielded higher drug permeation rates and
      increased its transference number at comparable pH. Transference number, however,
      was still approximately 1% at the highest current density, showing that
      concomitant ions from added electrolyte or extracted from the skin and the
      electrodes accounted for 99% of the total current. Further, transference number
      of the drug with polymaleic acid appeared to increase with current density. The
      fluxes obtained for both electrolyte systems with the present experimental
      arrangement could be extrapolated to deliver therapeutically relevant doses of
      the drug.

PMID- 15245887
TI  - Oral delivery of macromolecules using intestinal patches: applications for
      insulin delivery.
AB  - Oral drug delivery, though attractive compared to injections, cannot be utilized
      for the administration of peptides and proteins due to poor epithelial
      permeability and proteolytic degradation within the gastrointestinal tract. A
      novel method is described that utilizes mucoadhesive intestinal patches to
      deliver therapeutic doses of insulin into systemic circulation. Intestinal
      patches localize insulin near the mucosa and protect it from proteolytic
      degradation. In vitro experiments confirmed the secure adhesion of patches to the
      intestine and the release of insulin from the patches. In vivo experiments
      performed via jejunal administration showed that intestinal insulin patches with
      doses in the range of 1-10 U/kg induced dose-dependent hypoglycemia in normal
      rats with a maximum drop in blood glucose levels of 75% observed at a dose of 10
      U/kg. These studies demonstrate that reduction in blood glucose levels comparable
      to that induced by subcutaneous injections can be achieved via enteral insulin
      absorption with doses only 2-10-fold higher than subcutaneous doses.

PMID- 15245888
TI  - Incorporation and controlled release of a hydrophilic antibiotic using
      poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds.
AB  - The successful incorporation and sustained release of a hydrophilic antibiotic
      drug (Mefoxin, cefoxitin sodium) from electrospun poly(lactide-co-glycolide)
      (PLGA)-based nanofibrous scaffolds without the loss of structure and bioactivity
      was demonstrated. The morphology and density of the electrospun scaffold was
      found to be dependent on the drug concentration, which could be attributed to the
      effect of ionic salt on the electrospinning process. The drug release behavior
      from the electrospun scaffolds and its antimicrobial effects on Staphylococcus
      aureus cultures were also investigated. In all tested scaffolds, the maximum
      dosage of drug was released after 1 h of incubation in water at 37 degrees C. The
      usage of the amphiphilic block copolymer (PEG-b-PLA) reduced the cumulative
      amount of the released drug at earlier time points and prolonged the drug release
      rate at longer times (up to a 1-week period). The antibiotic drug released from
      these electrospun scaffolds was effective in their ability to inhibit
      Staphylococcus aureus growth (>90%). The combination of mechanical barriers based
      on non-woven nanofibrous biodegradable scaffolds and their capability for local
      delivery of antibiotics increases their desired utility in biomedical
      applications, particularly in the prevention of post-surgical adhesions and
      infections.

PMID- 15245889
TI  - Iontophoretic delivery of 5-aminolevulinic acid and its methyl ester using a
      carbopol gel as vehicle.
AB  - The aim of this study was to evaluate a Carbopol gel as a vehicle for
      iontophoretic delivery of 5-aminolevulinic acid (ALA) and its methyl ester (m
      ALA). The formulation was characterized rheologically and the passive diffusion
      of ALA and m-ALA in the gels was measured. Addition of ALA and m-ALA did not
      change the rheological behavior of the gel and the diffusion coefficients of ALA
      and m-ALA were 4.4 +/- 1.2 x 10(-6) and 3.08 +/- 0.7 x 10(-7) cm2 s(-1),
      respectively. The anodal iontophoretic transport of ALA and m-ALA through porcine
      skin in vitro was followed for 15 h at a constant current of 0.4 mA. When
      incorporating ALA in the gel, the steady-state was reached in 10-12 h at a flux
      level of approx. 65 nmol cm(-2) h(-1) compared to 2.5-4 h and a level of
      approximately 145 nmol cm(-2) h(-1) for m-ALA. The total amount of m-ALA
      delivered after 15 h of iontophoresis resulted in a six-fold enhancement over ALA
      delivery. Iontophoretic delivery from the gel formulation seems to be better
      than, or comparable to, the passive delivery from formulations commonly used
      clinically, in spite of the 10-20 times lower concentration of the drug in the
      gel formulation. The skin uptake after iontophoresis for m-ALA showed a nine-fold
      increase over that of ALA in the stratum corneum (SC).

PMID- 15245890
TI  - In vitro study of release mechanisms of paclitaxel and rapamycin from drug
      incorporated biodegradable stent matrices.
AB  - We have studied the in vitro release kinetics of two important antirestenosis
      drugs from biodegradable stent matrices. A helical stent incorporating drugs was
      exposed to buffer, and both degradation-controlled and diffusion-controlled drug
      releases were observed. New methods for in vitro drug release for both paclitaxel
      and rapamycin have been developed. The release profile shows a slow diffusion
      controlled phase, followed by a more rapid degradation-controlled region. In the
      early part of the drug release, no burst effect is observed for either drug. This
      might be significant for paclitaxel administration, where cardiotoxicity has been
      sometimes of concern. By suitable polymer/drug formulations, it is possible to
      develop controlled release stent matrices that can exhibit a variety of release
      profiles. These release profiles may have relevance to antirestenotic effects and
      to local or systemic toxic effects.

PMID- 15245891
TI  - Pharmacoscintigraphic evaluation of riboflavin-containing microballoons for a
      floating controlled drug delivery system in healthy humans.
AB  - Hollow microspheres (microballoons) floating on artificial gastric juice were
      developed as a floating controlled drug delivery system in the stomach. The
      intragastric behavior of 99mTc labelled microballoons (MB) and nonfloating
      microspheres (NF) (control) following oral administration in fasted and fed
      humans was investigated by gamma scintigraphy. Simultaneously, pharmacokinetic
      examination of riboflavin released from MB and NF was conducted in fasted and fed
      human subjects. In the fed state, MB were dispersed in the upper portion of the
      stomach; moreover, MB were retained in the stomach up to 300 min compared with
      NF, which descended gradually into the lower part of stomach within 90 min. In
      the fasted state, MB floated for approximately 60 min, after which it was removed
      rapidly via the cyclic activity referred to as the interdigestive migrating motor
      complex (IMMC). NF were removed more rapidly, i.e., within 60 min.
      Pharmacokinetic parameters, e.g., excretion half-life time (t1/2) and total
      urinary excretion, were well correlated with the gastric residence time (GRT)
      determined by the gamma scintigraphy analysis. The present investigation suggests
      that MB are very useful for improving drug bioavailability, resulting in a more
      sustained pharmacological action.

PMID- 15245892
TI  - Biodistribution of pH-responsive liposomes for MRI and a novel approach to
      improve the pH-responsiveness.
AB  - The potential of pH-sensitive paramagnetic liposomes as a probe for monitoring
      acidic pH in tumours with magnetic resonance imaging has recently been
      demonstrated. If the blood retention time is prolonged, such liposomes can
      accumulate in tumour interstitium due to increased vascular permeability and
      interstitial retention. In the present study, biodistribution studies in healthy
      rats showed rapid clearance of the pH-sensitive system
      dipalmitoylphosphatidylethanolamine (DPPE)/dipalmitoylglycerosuccinate (DPSG)
      liposomal GdDTPA-BMA from the blood circulation with most of the Gd dose in the
      liver at 15 min post intravenous injection. Incorporation of 1.5 mol%
      polyethylene glycol (PEG) grafted DPPE (DPPE-PEG) in the above-mentioned
      formulation resulted in a significantly prolonged blood circulation time.
      However, the relaxometric pH-response of the DPPE/DPSG/DPPE-PEG system decreased
      as a function of mol% DPPE-PEG. Therefore, a compromise would be necessary
      between long blood residence time and a suitable pH-sensitivity of the liposomes.
      A possible approach to compensate for the reduced pH-sensitivity was
      investigated. Gadofosveset, a low-molecular weight Gd-chelate with high affinity
      for albumin, was encapsulated within DPPE/DPSG liposomes. This promising system
      showed in blood a markedly higher relaxometric response than the corresponding
      system with GdDTPA-BMA, due to release of gadofosveset at low pH and subsequent
      binding to albumin.

PMID- 15245893
TI  - Effect of drug physicochemical properties on swelling/deswelling kinetics and
      pulsatile drug release from thermoresponsive poly(N-isopropylacrylamide)
      hydrogels.
AB  - The effect of drug physicochemical properties on swelling/deswelling kinetics and
      pulsatile drug release from a thermoresponsive hydrogel was examined. Hydrogels
      were loaded with drug and thermally triggered swelling/deswelling and release
      experiments were performed. Two series of drugs of contrasting hydrophilicity and
      varying physicochemical properties were examined. Benzoic acid (BA), its methyl
      and propyl esters, and diltiazem base were used as model hydrophobic drugs.
      Sodium benzoate (NaB), diltiazem HCl (DHCl), vitamin B12 (VB12) and various
      dextrans (MW 4300, 10,200, 42,000, 68,800) were used as model hydrophilic agents
      of increasing size. The hydrogel swelling rate was slowed by the presence of the
      hydrophobic drugs and this decreased rate was solubility dependant for the
      benzoates. The hydrophilic series increased the rate of swelling compared to the
      unloaded system. In all cases, the magnitude and rate of hydrogel contraction
      were proportional to the extent of swelling prior to temperature switch. Drug
      release was by diffusion below the lower critical solution temperature (LCST),
      while a solubility-dependent drug pulse release on temperature switch was
      observed for the hydrophobic series. Effectiveness of thermal control of
      hydrophobic drug release increased with increasing solubility. The hydrophilic
      series produced a molecular size-dependent drug pulse on temperature switch above
      the LCST. Pulsatile on-off drug release was shown with DHCl, VB12 and the various
      dextrans. Drug solubility, size and chemical nature were shown to be of
      particular importance in the control of hydrogel swelling and drug release from
      thermosensitive hydrogels.

PMID- 15245894
TI  - Comparative study on sustained release of human growth hormone from semi
      crystalline poly(L-lactic acid) and amorphous poly(D,L-lactic-co-glycolic acid)
      microspheres: morphological effect on protein release.
AB  - Recombinant human growth hormone (rhGH) was encapsulated by a double emulsion
      solvent evaporation method within two biodegradable microspheres having different
      polymer compositions. Semi-crystalline poly(L-lactic acid) (PLA) and amorphous
      poly(D,L-lactic-co-glycolic acid) (PLGA) were used for the encapsulation of hGH.
      Protein release profiles from the two microspheres were comparatively evaluated
      with respect to their morphological difference. Both of the microspheres
      similarly exhibited rugged surface and porous internal structures, but their
      inner pore wall morphologies were quite different. The slowly degrading PLA
      microspheres had many nano-scale reticulated pores on the wall, while the
      relatively fast degrading PLGA microspheres had a non-porous and smooth wall
      structure. From the PLA microspheres, hGH was released out in a sustained manner
      with an initial approximately 20% burst, followed by constant release, and almost
      100% complete release after a 1-month period. In contrast, the PLGA microspheres
      showed a similar burst level of approximately 20%, followed by much slower
      release, but incomplete release of approximately 50% after the same period. The
      different hGH release profiles between PLA and PLGA microspheres were attributed
      to different morphological characters of the pore wall structure. The inter
      connected nano-porous structure of PLA microspheres was likely to be formed due
      to the preferable crystallization of PLA during the solvent evaporation process.

PMID- 15245895
TI  - Correlation of transdermal iontophoretic phenylalanine and mannitol transport:
      test of the internal standard concept under DC iontophoresis and constant
      resistance AC iontophoresis conditions.
AB  - The purpose of this study was to test the feasibility of using an internal
      standard approach to predict the transdermal flux of phenylalanine (Phe) across
      human epidermal membrane (HEM) in vitro during iontophoresis of constant direct
      current (DC), constant skin resistance alternating current (AC) with DC offset
      (AC-plus-DC), symmetric constant resistance AC (AC-only), and constant current DC
      with the application of a polyelectrolyte. Under the constant current DC and AC
      plus-DC conditions, a linear relationship between the permeation of Phe and that
      of mannitol was observed with a slope close to unity. The ratios of the Phe
      permeability coefficients to those of mannitol during iontophoresis with
      different HEM samples were essentially constant with significantly smaller inter
      sample and intra-sample variabilities than those of the raw Phe permeability
      coefficient data. This demonstrates that mannitol is a good internal standard for
      predicting the transdermal iontophoretic flux of Phe under these two conditions.
      On the other hand, the correlations of the permeability coefficients of Phe and
      mannitol under the AC-only iontophoresis and iontophoresis with the
      polyelectrolyte are poorer than those observed during DC and AC-plus-DC
      iontophoresis. The poor correlations are believed to be related to Phe being a
      zwitterion and its anionic form in HEM. Previously, iontophoretic transport of
      glucose has been demonstrated to be essentially the same as that of mannitol. The
      good correlations between Phe and mannitol transport across HEM during DC and AC
      plus-DC iontophoresis in the present study therefore suggest that glucose and its
      extraction can be used as the internal standard for iontophoretic Phe monitoring.

PMID- 15245896
TI  - A mathematical model of volatile release in mouth from the dispersion of gelled
      emulsion particles.
AB  - This paper presents a mathematical model of in-mouth volatile release from gelled
      emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS
      Breath analysis is presented to demonstrate the effect of particle size, oil
      content and oil-water partition coefficients. It is shown that in-mouth release
      of aroma from the dispersion of gelled emulsion particles follows a two-component
      kinetic equation with fast and slow components. Both the fast and slow rate
      constants depend on the particle size, oil content and oil water partition
      coefficient of the aroma. The relative amount of aroma contributing to the fast
      and slow components also depends on the size of the particles. In order to
      understand this unexpected behaviour, an analytical model was developed that
      considers the interplay between the mass transfer of flavour across the interface
      of the particles and that across the air-liquid interface. Analytical expressions
      for the two rate constants and the relative ratio of aroma contributing to the
      fast component have been derived. From this model, three regimes of in-mouth
      release of aroma from the dispersion of gelled emulsion particles were identified
      including, the emulsion regime, the transition regime and the gel particle
      regime. In the emulsion regime, changes in the size of gelled emulsion particles
      had negligible impact on the overall release. In the transition regime, the
      release was controlled by the interaction of flavour transfer from the particles
      with that across the air-water interface. In the gel particle regime, aroma
      release at long times was governed by the particles and that at short times was
      governed by the air-water interface, and the two processes were fully decoupled.
      A simple relationship was derived for the critical size above which the release
      of aroma from the dispersion of gelled emulsion particles is affected by the size
      of the particles.

PMID- 15245897
TI  - Tissue and intrahepatic distribution and subcellular localization of a
      mannosylated lipoplex after intravenous administration in mice.
AB  - We have previously reported that, unlike a lipoplex and mannosylated (Man)
      lipoplex underwent gene transfer to liver nonparenchymal cells (NPC) that possess
      mannose receptors after intravenous administration in mice. In this study, the
      tissue, intrahepatic distribution, and subcellular localization of the lipoplex
      after intravenous administration were investigated. DC-Chol liposome was selected
      as a cationic liposomes. After administration of lipoplex and Man lipoplex, the
      high gene expression was observed in the lung and liver, respectively. After
      administration of [32P]Man lipoplex, about 80% of [32P]plasmid DNA (pDNA) was
      accumulated in the liver. As for the intrahepatic distribution, the
      NPC/parenchymal cells (PC) ratio of [32P]Man lipoplex was 9.64, whereas the
      NPC/PC ratio of [32P]lipoplex was 1.93. The radioactivity in the cytosolic
      fraction of liver homogenate of [111In]Man lipoplex was two-fold higher than that
      of [111In]lipoplex, indicating that Man liposomes facilitate the release of pDNA
      into the cytosolic space. However, a rapid sorting of the radioactivity from
      endosomes to lysosomes was observed with the [111In]Man lipoplex. Also,
      amplification of pDNA by PCR suggested that the Man lipoplex is more rapidly
      degraded within the intracellular vesicles than the lipoplex. These results
      suggested that modulation of its intracellular sorting could improve the
      transfection efficiency of Man lipoplex.

PMID- 15245898
TI  - Protease-induced release of functional peptides from bioplexes.
AB  - Linking peptide functions directly to nucleic acids can be used to improve
      transfection. We have previously demonstrated this by sequence-specific
      hybridization of a bifunctional peptide nucleic acid (PNA) consisting of a
      nucleic acid binding moiety conjugated to a peptide. The resulting biological
      complex of PNA/DNA is called a Bioplex. The bifunctional PNA is continuously
      synthesized with one or more functional entities. For certain applications, it
      might be preferable to eliminate a functional entity after it has served its
      purpose. We have addressed this issue by adding a specific protease cleavage site
      to the construct. In this first approach, cathepsin L was used to cleave a linker
      sequence including a cathepsin L site: afrsaaq, thereby releasing the tri-peptide
      Arg-Gly-Asp (RGD) from the PNA anchor. In vitro and in vivo experiments showed an
      efficient cleavage of the peptide. Moreover, bifunctional PNA constructs were
      shown to retain activity of the second entity following removal of the first
      function. Since cathepsin L is ubiquitously expressed in eukaryotic cells and
      becomes active as the endosomal pH drops, inclusion of cathepsin sites makes it
      possible to remove functional entities in late endosomes/early lysosomes.

PMID- 15245899
TI  - Cationic lipid emulsions containing heavy oils for the transfection of adherent
      cells.
AB  - A new cationic emulsion system with high density was prepared increasing in vitro
      transfection efficiencies of adherent cells. Lipiodol with a density of 1.3
      (g/ml) was selected to increase the density of the DNA/emulsion complex. Cationic
      lipid emulsions were formulated with mixtures of lipiodol and squalene as the oil
      phase and 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a
      cationic lipid. These emulsions were used to find the correlation between the
      density and the in vitro transfection efficiency. The physical characteristics of
      the new emulsion formulations were also determined. Heavier DNA/cationic lipid
      emulsion complex showed higher in vitro transfection efficiency on adherent cell
      lines in the presence of 10% serum compared to lighter ones. The cationic lipid
      emulsion formulated with lipiodol and DOTAP was more stable and showed better in
      vitro transfection efficiency than other carriers without lipiodol. Due to the
      high density of the carrier, the DNA/carrier complex sank to the bottom of the
      wells, thereby increasing the contact between the complex and adherent cells. The
      new lipiodol emulsion with high density showed superior transfection activities
      on adherent cells in the presence of serum.

PMID- 15245900
TI  - Silence of the centromeres--not.
AB  - Centromeres are a conundrum; although many proteins associated with centomeres
      are conserved from yeast to humans, the underlying DNA sequence is not. A
      proposed solution to this problem is that an epigenetic, largely heterochromatic,
      state be imposed by these proteins. Recent analysis of a human neocentromere and
      the complete sequence of a rice centromere suggest that this epigenetic state can
      enable transcription of at least some genes within a centromere.

PMID- 15245901
TI  - Synthetic biology evolves.
AB  - Synthetic biology is advancing rapidly as biologists, physicists and engineers
      are combining their efforts to understand and program cell function. By
      characterizing isolated genetic components or modules, experimentalists have
      paved the way for more quantitative analyses of genetic networks. A recent paper
      presents a method of computational, or in silico, evolution in which a set of
      components can evolve into networks that display desired behaviors. An integrated
      approach that includes a strategy of in silico design by evolution, together with
      efforts exploiting directed evolution in vivo, is likely to be the next step in
      the evolution of synthetic biology.

PMID- 15245902
TI  - Double humanized yeast makes hydrocortisone.

PMID- 15245903
TI  - Hindsight rather than foresight: reality versus the EU draft guideline on
      pharmaceuticals in the environment.
AB  - The strategy of passing much of European Union (EU) waste water through a sewage
      treatment plant (STP) before discharging it into rivers or lakes has done much to
      improve the quality of our inland waterways. But we still face a very worrying
      situation. Environmental problems have surfaced in conjunction with the STPs and
      their effluent recipients, and attention has turned to human pharmaceuticals and
      endocrine active substances, in particular, as another source of potential
      pollutants. Trying to assess the detrimental effects of these chemicals on the
      aquatic environment represents an extreme cost in terms of animals, time and
      finance. Instead, it would be better to go back to basics and to prevent entry of
      these substances into our aquatic environment.

PMID- 15245904
TI  - Is confidence in the monitoring of GE foods justified?
AB  - Often the limits of detection of genetically engineered organisms (GEOs, LMOs,
      GMOs) determine what legislation sets as thresholds of allowable contamination of
      the human food chain with GEOs. Many countries have legislation that is triggered
      by certain thresholds of contamination. Importantly, international trade in food
      and animal feed is becoming increasingly vulnerable to interruptions caused by
      the ambiguity GEOs can create when shipments are monitored at the border. We
      examine the tools available for detection. Four key error-generating stages are
      identified with the aim of prompting a higher uniform standard of routine
      analysis at export and import points. Contamination of the New Zealand corn crop
      with GEOs is used as a case study for the application of monitoring tools and
      vulnerability to errors. These tools fail to meet emerging food safety
      requirements, but some improvements are in development.

PMID- 15245905
TI  - Biotechnology and the popular press: hype and the selling of science.
AB  - The popular media has emerged as an important source of scientific information.
      It has been suggested that the portrayal of genetics by the media is often
      inaccurate--a phenomenon branded 'genohype'--and, as a result, is having an
      adverse impact on public understanding and policy development. However, emerging
      data suggest that, in some circumstances, the media reporting of science is
      surprisingly accurate and portrays a message created by the scientific community.
      As such, there are reasons to believe that the hyping of research results might
      be part of a more systemic problem associated with the increasingly commercial
      nature of the research environment.

PMID- 15245906
TI  - Therapeutic potential of vitamin D-binding protein.
AB  - Vitamin D-binding protein (DBP) is a multi-functional plasma protein with many
      important functions. These include transport of vitamin D metabolites, control of
      bone development, binding of fatty acids, sequestration of actin and a range of
      less-defined roles in modulating immune and inflammatory responses. Exploitation
      of the unique properties of DBP could enable the development of important
      therapeutic agents for the treatment of a variety of diseases.

PMID- 15245907
TI  - Codon bias and heterologous protein expression.
AB  - The expression of functional proteins in heterologous hosts is a cornerstone of
      modern biotechnology. Unfortunately, proteins are often difficult to express
      outside their original context. They might contain codons that are rarely used in
      the desired host, come from organisms that use non-canonical code or contain
      expression-limiting regulatory elements within their coding sequence.
      Improvements in the speed and cost of gene synthesis have facilitated the
      complete redesign of entire gene sequences to maximize the likelihood of high
      protein expression. Redesign strategies are discussed here, including
      modification of translation initiation regions, alteration of mRNA structural
      elements and use of different codon biases.

PMID- 15245908
TI  - Scaffold-based tissue engineering: rationale for computer-aided design and solid
      free-form fabrication systems.
AB  - One of the milestones in tissue engineering has been the development of 3D
      scaffolds that guide cells to form functional tissue. Recently, mouldless
      manufacturing techniques, known as solid free-form fabrication (SFF), or rapid
      prototyping, have been successfully used to fabricate complex scaffolds.
      Similarly, to achieve simultaneous addition of cells during the scaffold
      fabrication, novel robotic assembly and automated 3D cell encapsulation
      techniques are being developed. As a result of these technologies, tissue
      engineered constructs can be prepared that contain a controlled spatial
      distribution of cells and growth factors, as well as engineered gradients of
      scaffold materials with a predicted microstructure. Here, we review the
      application, advancement and future directions of SFF techniques in the design
      and creation of scaffolds for use in clinically driven tissue engineering.

PMID- 15245909
TI  - Recent advances in enzyme assays.
AB  - Enzyme assays for high-throughput screening and enzyme engineering, which are
      often based on derivatives of coumarin, nitrophenol, fluorescein,
      nitrobenzofurazane or rhodamine dyes, can be divided into two categories: those
      that depend on labelled substrates, and those that depend on sensing the
      reactions of unmodified substrates. Labelled substrates include, for example,
      fluorogenic and chromogenic substrates that generate a reporter molecule by beta
      elimination, fluorescence resonance energy transfer (FRET) substrates and
      isotopic labels for enantioselectivity screening. By contrast, endpoint sensing
      can be done using amine reagents, fluorescent affinity labels for phosphorylated
      proteins, or synthetic multifunctional pores. Sensing assays can also be done in
      real time by using, for example, aldehyde trapping to follow vinyl ester
      acylation in organic solvent or calcein-copper fluorescence for sensing amino
      acids. The current trend is to assemble many such assays in parallel for enzyme
      profiling and enzyme fingerprinting.

PMID- 15245910
TI  - Modular protein engineering for non-viral gene therapy.
AB  - Despite the recognized potential of viral vectors for gene therapy, growing
      biological concerns are prompting the exploration of safer, non-viral vectors to
      deliver therapeutic nucleic acids. In this context, recombinant proteins can be
      bioproduced on a large scale, without the need for further in vitro
      modifications, being free of known or suspected biohazards. For these vehicles to
      act as efficient gene-delivery devices, they must perform relevant functions that
      mimic those of viruses; namely, nucleic acid condensation, targeted cell
      attachment and internalization, endosomal escape and nuclear transfer. Modular
      engineering enables the construction of chimeric polypeptides in which selected
      domains, potentially from different origins, provide the required activities. An
      equilibrate combination and spatial distribution of such partner elements has
      generated promising prototypes, able to deliver expressible DNA to tissue culture
      but also to specific cell-types in whole organisms.

PMID- 15245911
TI  - Characterization of the prothrombin gene expression during nerve differentiation.
AB  - The transcriptional regulation of the prothrombin gene expression in
      neuroblastomas was investigated because of the interest in non-hepatic thrombin
      expression and function in the nervous system. The data indicated that the murine
      prothrombin gene was distinctively transcribed in proliferating murine N2a cells
      and that the transcripts were decreased during the differentiation of N2a cells.
      The gene transcription in proliferating N2a cells was due to the C-I nuclear
      complex formation in the promoter region, -248/-140. Mutation analyses indicated
      that nucleotides from -237 to -231 are the core C-I binding site while the longer
      sequence -248/-140 is needed for the C-I binding. The C-I binding to the promoter
      -248/-140 could be inhibited by the presence of competitor probe -187/-166, and
      the mutation in nucleotides from -186 to -179 significantly diminished not only
      the formation of C-I binding in the promoter region but also the promoter
      activity in proliferating neuroblastoma cells. Cyclic AMP response element (CRE)
      modulator, CREM, appeared to selectively bind to the sequence encompassing -186/
      179. Taken together, the results indicate that the prothrombin gene transcription
      in proliferating N2a cells was critically dependent on the cooperative
      interaction between the factor(s) binding to the C-1 cis-acting element (-237/
      231) and the putative CRE site (-186/-179) in the prothrombin promoter, and that
      the lack of prothrombin expression that coincided with nerve differentiation was
      mainly due to the lack of C-I complex formation in the promoter.

PMID- 15245912
TI  - Analysis of gene expression in the bovine corpus luteum through generation and
      characterisation of 960 ESTs.
AB  - To gain new insights into gene identity and gene expression in the bovine corpus
      luteum (CL) a directionally cloned CL cDNA library was constructed, screened with
      a total CL cDNA probe and clones representing abundant and rare mRNA transcripts
      isolated. The 5'-terminal DNA sequence of 960 cDNA clones, composed of 192
      abundant and 768 rare mRNA transcripts was determined and clustered into 351 non
      redundant expressed sequence tag (EST) groups. Bioinformatic analysis revealed
      that 309 (88%) of the ESTs showed significant homology to existing sequences in
      the protein and nucleotide public databases. Several previously unidentified
      bovine genes encoding proteins associated with key aspects of CL function
      including extracellular matrix remodelling, lipid metabolism/steroid biosynthesis
      and apoptosis, were identified. Forty-two (12%) of the ESTs showed homology with
      human or with other uncharacterised ESTs, some of these were abundantly expressed
      and may therefore play an important role in primary CL function. Tissue
      specificity and temporal CL gene expression of selected clones previously
      unidentified in bovine CL tissue was also examined. The most interesting finds
      indicated that mRNA encoding squalene epoxidase was constitutively expressed in
      CL tissue throughout the oestrous cycle and 7-fold down-regulated (P < 0.05) in
      late luteal tissue, concomitant with the disappearance of systemic progesterone,
      suggesting that de novo cholesterol biosynthesis plays an important role in
      steroidogenesis. The mRNA encoding the growth factor, insulin-like growth factor
      binding protein-related protein 1 (IGFBP-rP1), remained constant during the
      oestrous cycle and was 1.8-fold up-regulated (P < 0.05) in late luteal tissue
      implying a role in CL regression.

PMID- 15245913
TI  - Dipeptidyl peptidase 9 has two forms, a broad tissue distribution, cytoplasmic
      localization and DPIV-like peptidase activity.
AB  - Dipeptidyl peptidase (DP) IV has a distinct substrate specificity in hydrolyzing
      a post-proline bond. Here we present novel data on the sizes and tissue
      distribution of human and rat gene products and the peptidase activity of the
      DPIV-related gene DP9. A short cDNA of 2589 bp and a long cDNA of 3006 bp of DP9
      were cloned. A ubiquitous predominant DP9 mRNA transcript at 4.4 kb represented
      the short form, whereas a less abundant 5.0-kb transcript present predominantly
      in muscle represented the long form. Both forms of DP9 have no transmembrane
      domain and two potential N-linked glycosylation sites. DP9 exhibited post-proline
      dipeptidyl aminopeptidase activity and was a cytoplasmic, 110-kDa monomer. Thus,
      the six DPIV gene family members have diverse characteristics: only DP9 and DP8
      have exclusively cytoplasmic localization and only DP9, DP8, fibroblast
      activation protein (FAP) and DPIV have peptidase activity.

PMID- 15245914
TI  - Molecular identification and expression of two non-P450 enzymes, monoamine
      oxidase A and flavin-containing monooxygenase 2, involved in phase I of
      xenobiotic biotransformation in the Pacific oyster, Crassostrea gigas.
AB  - Marine bivalve metabolism can be perturbed by hydrocarbon and pesticide pollution
      in coastal ecosystems. In this study, in the Pacific oyster, Crassostrea gigas,
      full-length cDNAs encoding two non-P450 phase I enzymes, flavin-containing
      monooxygenase 2 (FMO-2) and monamine oxidase A (MAO A), were characterized. Both
      sequences contained the co-factor fixation motifs characteristic of their
      respective enzyme families. Using reverse transcription polymerase chain reaction
      (RT-PCR), the messenger RNA (mRNA) transcription levels of these two enzymes in
      tissues of oysters exposed, under experimental conditions, to hydrocarbons and
      two pesticide treatments were investigated. The pesticide treatments were
      exposure to either glyphosate or to a mixture composed of atrazine, diuron and
      isoproturon. The results showed a strong differential expression of FMO-2 and MAO
      A that was both tissue-specific as well as time- and treatment-dependent. It was
      also clearly demonstrated that the transcription levels of MAO A (generally
      considered a constitutive enzyme without external regulation) were induced by
      hydrocarbons and pesticides in digestive gland and inhibited by pesticides in
      gill tissue. Furthermore, the transcription levels of FMO-2 and MAO A mRNA in
      digestive gland might be useful as a marker of hydrocarbon or pesticide exposure
      in monitoring programs.

PMID- 15245915
TI  - A conserved initiator element on the mammalian poly(ADP-ribose) polymerase-1
      promoters, in combination with flanking core elements, is necessary to obtain
      high transcriptional activity.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a conserved nuclear protein present in
      nearly all eukaryotes. In mammalian cells, its abundant expression and its
      ability to specifically bind to DNA strand breaks make it an important enzyme in
      the rapid cellular response to DNA damage. Although the promoter regions of the
      three known mammalian PARP-1 genes, from human, rat and mouse, are different,
      they share common features, such as multiple GC-rich regions, lack of a
      functional TATA box, and presence of a putative initiator element. In this study,
      we analyzed the core promoter region of the rat PARP-1 gene, and show that it
      contains a functional initiator element surrounding the transcription start site.
      This core element lies within an approximately 40-base-pair region that is highly
      conserved in all three mammalian PARP-1 promoters. Furthermore, we show that
      other core elements located upstream and downstream of the PARP-1 initiator,
      including a functional Sp1 target site, synergize to regulate rat PARP-1
      transcription. As the initiator region of all three PARP-1 gene promoters is
      highly conserved, their transcriptional regulation is likely achieved through
      similar mechanisms.

PMID- 15245916
TI  - Cloning of zebrafish metallothionein gene and characterization of its gene
      promoter region in HepG2 cell line.
AB  - The coding region of cDNA and genomic DNA, with its promoter region, of zebrafish
      metallothionein (zMT) gene homologous to the piscine MT-II was obtained. The A/T
      rich promoter region contains four metal regulatory elements (MREs), three
      activator protein 1 (AP1) and one specific protein 1 (Sp1) binding sites. The
      four MREs are organized into two clusters, a distal cluster with one MRE lying
      around 740 bp upstream of the transcription start point and a proximal cluster
      with three MREs located close to the TATA box. The metal induction ability of the
      promoter was assessed by transient luciferase gene expression assays in HepG2
      cells. The zMT promoter was inducible by Zn2+, Cd2+, Cu2+ and Hg2+ ions in
      decreasing inducibility, while inert to Ni2+, Pb2+ and Co2+ ions, and H2O2
      treatment in vitro. Deletion of the putative cis-acting elements in the promoter
      region revealed that the distal MRE (MREd) was important in mediating metal
      inducibility. Despite the binding of HepG2 cell nuclear protein factors to all
      MREs as confirmed by electrophoretic mobility shift assay (EMSA), the proximal
      MREs did not provide significant contribution to metal induction of zMT gene in
      HepG2 cells. The metal inducibility of zMT promoter required the cooperative
      effect of at least three MRE sites.

PMID- 15245917
TI  - Extraction of information on the buildup and consumption of reactive
      intermediates from quadruplex DNA assembly time courses.
AB  - A method was developed to detect the time course of the overall presence of
      intermediate species during K+-induced DNA quadruplex assembly from single
      stranded d(TG4) oligonucleotides in experiments in which only the combined
      circular dichroisms (CD) of all species present could be measured directly. The
      presence of intermediate species is determined unambiguously but quantitative
      estimates can be made only to the extent that the CD characteristics of all
      intermediates are known. The method consists of (i) obtaining CD spectra of known
      concentrations of initial and final species to determine their molar ellipticity
      coefficients, (ii) carrying out CD measurements of the kinetics of quadruplex
      assembly reactions at two different wavelengths, chosen to give optimal
      differentiation between the initial and final species, and (iii) using the
      results of (ii) to detect discrepancies between the rates of consumption of
      single strands and the generation of quadruplex to infer the presence of
      intermediate species. The analysis was facilitated by the validation and use of
      biphasic exponential expressions obtained from the SAS nonlinear curve fitting
      procedure NLIN in place of the raw CD data. The general method is described, then
      applied to data from [d(TG4)4.(K+)3] quadruplex assembly experiments.

PMID- 15245918
TI  - Cloning, expression, and pore-forming properties of mature and precursor forms of
      pleurotolysin, a sphingomyelin-specific two-component cytolysin from the edible
      mushroom Pleurotus ostreatus.
AB  - Pleurotolysin, a sphingomyelin-specific cytolysin consisting of A (17 kDa) and B
      (59 kDa) components from the basidiomycete Pleurotus ostreatus, assembles into a
      transmembrane pore complex. Here, we cloned complementary and genomic DNAs
      encoding pleurotolysin, and studied pore-forming properties of recombinant
      proteins. The genomic regions encoding pleurotolysin A and B contained two and
      eight introns, respectively, and putative promoter sequences. The complementary
      DNA (cDNA) for pleurotolysin A encoded 138 amino acid residues, and the predicted
      product was identical with natural pleurotolysin A, except for the presence of
      the first methionine. Recombinant pleurotolysin A lacking the first methionine
      was purified as a 17-kDa protein with sphingomyelin-binding activity. The cDNA
      for pleurotolysin B encoded a precursor consisting of 523 amino acid residues, of
      which N-terminal 48 amino acid residues were absent in natural pleurotolysin B.
      Mature and precursor forms of pleurotolysin B were expressed as insoluble 59- and
      63-kDa proteins, respectively, which were unfolded with 8 M urea and refolded by
      100-fold dilution with 10 mM Tris-HCl buffer, pH 8.5. Although neither
      recombinant pleurotolysin A nor B alone was hemolytically active at higher
      concentrations of up to 100 mg/ml, they cooperatively assembled into a membrane
      pore complex on human erythrocytes and lysed the cell as efficiently as the
      natural proteins at nanomolar concentrations. In contrast, the precursor of
      pleurotolysin B was much less hemolytically active than mature pleurotolysin B in
      the presence of pleurotolysin A.

PMID- 15245919
TI  - Molecular cloning and characterization of a cDNA encoding a kinase in Cucumis
      sativus and its expression by abiotic stress treatments.
AB  - As a part of an integrated study of stress-related gene expression, a cDNA clone
      coding for a protein kinase in the root of Cucumis sativus was isolated and
      characterized with respect to its sequence and the expression patterns upon
      various abiotic stress treatments. The predicted polypeptide of 352 amino acid
      residues contains characteristic features of both the serine/threonine and
      tyrosine kinase families. In vitro kinase assay confirmed that the isolated
      protein kinase has autophosphorylation activity. Southern blot analysis showed
      that the kinase gene is a single-copy gene. Northern blot analysis showed that
      the kinase gene was more abundantly expressed in the roots and shoots than in the
      leaves. A quantitative real-time reverse-transcription-polymerase chain reaction
      analysis revealed that, among the abiotic stresses tested, drought treatment
      markedly decreased the transcript level of the kinase, whereas the expression of
      the kinase gene significantly increased by cold treatment. High salinity did not
      influence its expression. The present report identifies a dual specificity
      protein kinase in cucumber that shows different responses to abiotic stress
      treatments.

PMID- 15245920
TI  - Characterization of a novel selenium methyltransferase from freshwater bacteria
      showing strong similarities with the calicheamicin methyltransferase.
AB  - A novel group of Se-methyltransferases is presented. The genetic determinant,
      named mmtA, which revealed this group was isolated from selenite and selenate
      resistant freshwater bacteria. E. coli expressing mmtA and grown with a Se
      supplement emitted dimethyl selenide (DMSe) and dimethyl diselenide (DMDSe).
      Phylogenetic analysis divided MmtA-like bacterial sequences into two clusters,
      one grouping MmtA with S- and O-methyltransferases, and one grouping UbiE C
      methyltransferases. Se methylation by some of these MmtA phyletic neighbours was
      investigated.

PMID- 15245922
TI  - Botulinum toxin: a new dimension in the treatment of lower urinary tract
      dysfunction.

PMID- 15245923
TI  - Update on ureteral stents.

PMID- 15245924
TI  - Endopyeloplasty versus endopyelotomy versus laparoscopic pyeloplasty for primary
      ureteropelvic junction obstruction.
AB  - OBJECTIVES: To present our intermediate-term (1-year) data on endopyeloplasty and
      retrospectively compare it with endopyelotomy and laparoscopic pyeloplasty in 44
      patients with primary ureteropelvic junction (UPJ) obstruction. Endopyeloplasty,
      horizontal percutaneous suturing of a conventional longitudinal endopyelotomy
      incision, is a promising novel option for minimally invasive management of UPJ
      obstruction. We recently developed the technique and demonstrated the clinical
      feasibility of percutaneous endopyeloplasty. METHODS: At our two institutions, 44
      consecutive, nonrandomized patients with primary UPJ obstruction underwent
      percutaneous endopyeloplasty (n = 15; group 1), percutaneous endopyelotomy (n =
      15; group 2), or laparoscopic dismembered pyeloplasty (n = 14; group 3). The
      study inclusion criteria were short segment (less than 1 cm) stenosis, no prior
      surgery for UPJ obstruction, and no crossing vessels in groups 1 and 2. The mean
      patient age was 30.3, 38.6, and 38.9 years and the duration of symptoms was 5.5,
      6, and 6.6 months in groups 1, 2, and 3, respectively. Postoperative success was
      evaluated by symptoms, intravenous urography, and/or diuretic renography.
      RESULTS: The mean operative time was 119 minutes in group 1, 52 minutes in group
      2, and 243 minutes in group 3 (P <0.001). Complications occurred in 3 patients in
      group 1 (fever in 2 and fluid extravasation in 1), 2 patients in group 2
      (bleeding in 1 and urinoma in 1), and no patients in group 3. The duration of
      double-J stent placement was 2, 4, and 6 weeks in groups 1, 2, and 3,
      respectively. A resolution of symptoms and unobstructed drainage on intravenous
      urography and/or diuretic renography was noted in 100% and 100% of patients in
      group 1 (mean follow-up 11.6 months), 93% and 88% of patients in group 2 (mean
      follow-up 31.4 months), and 93% and 100% of patients in group 3 (mean follow-up
      20 months). CONCLUSIONS: The results of this retrospective comparison of patients
      with primary UPJ obstruction suggest that percutaneous endopyeloplasty may have
      functional superiority over percutaneous endopyelotomy. The technical simplicity
      and shorter operative time of endopyeloplasty are advantages compared with
      laparoscopic pyeloplasty. Endopyeloplasty may be associated with a shorter
      duration of stenting compared with the other techniques. Longer term follow-up in
      a larger group of patients from multiple centers and a prospective randomized
      comparison among these various minimally invasive approaches are necessary to
      validate these preliminary results.

PMID- 15245926
TI  - Minimally invasive therapy for renal cell carcinoma: is there a new community
      standard?
AB  - OBJECTIVES: To evaluate current practice use of laparoscopic and minimally
      invasive therapies in the treatment of renal cell cancer. METHODS: A
      questionnaire was sent to 174 members of the Minnesota Urological Society. The
      first case scenario described a 6-cm lesion not amenable to nephron-sparing
      surgery. The second case scenario described a 3-cm lower pole exophytic mass
      amenable to nephron-sparing surgery. The treatment options included traditional
      therapy (open partial or radical nephrectomy) and minimally invasive therapy
      (laparoscopic radical or partial nephrectomy or renal cryoablation). RESULTS: Our
      survey response rate was 49%. For the first scenario, 86% of respondents would
      offer open radical nephrectomy; however, 57% would offer laparoscopic surgery. Of
      those urologists offering laparoscopic surgery, 14% would refer outside their
      practice and 43% would use a hand-assisted approach. Sixty-four percent of the
      metropolitan and 56% of the urban respondents would offer a form of minimally
      invasive therapy; only 29% of rural respondents offered these options. For the
      second scenario, 90% of respondents would offer open partial nephrectomy and 45%
      a minimally invasive therapy; however, 24% of these would refer outside their
      practice. Thirty-eight percent of respondents would offer laparoscopic partial
      nephrectomy and 22% of respondents would offer renal cryoablation. Urologists
      completing residency after 1990 were more likely to offer a minimally invasive
      option (65%) compared with urologists completing residency before 1990 (31%).
      CONCLUSIONS: Minimally invasive therapy for renal cell cancer is evolving into a
      community standard of care, with urologists relying heavily on outside referrals
      to access minimally invasive alternatives. Younger urologists living in
      metropolitan and urban areas are more likely to offer minimally invasive therapy.
      Additional emphasis should be placed on increasing the availability of minimally
      invasive techniques in rural settings.

PMID- 15245927
TI  - Retroperitoneoscopic partial nephrectomy with transient occlusion of renal artery
      for treatment of small renal tumors.
AB  - OBJECTIVES: To evaluate the results of retroperitoneoscopic partial nephrectomy
      with transient occlusion of the renal artery for treatment of patients with small
      renal tumors. METHODS: From May 2002 to March 2003, 12 consecutive patients with
      T1N0M0 renal tumors with a median diameter of 3.0 cm underwent
      retroperitoneoscopic partial nephrectomy. The renal artery was clamped
      transiently without occlusion of the renal vein and the tumor was excised with
      scissors. Intracorporeal renal cooling was achieved by cold saline perfusion of
      the renal pelvis through a single-J ureteral catheter. Hemostasis was achieved by
      approximating the renal parenchyma over the perirenal fatty tissue using a
      retroperitoneoscopic suturing technique. RESULTS: Of the 12 patients, 11
      successfully underwent partial nephrectomy retroperitoneoscopically. The median
      operative time, renal ischemic time, and amount of blood loss in the successful
      procedures was 220 minutes (range 132 to 340), 50 minutes (range 16 to 115), and
      150 mL (range 50 to 800), respectively. The renal calix was opened and repaired
      in 10 patients. The surgical margin was negative in all patients. The
      postoperative course was uneventful in all patients, and the return to work was
      achieved in a median of 18 days (range 9 to 39). The renal function of the
      affected kidney was well preserved postoperatively, when examined by renal
      scintigraphy. Neither local recurrence nor distant metastasis was found during
      the median follow-up period of 10 months (range 1 to 18). CONCLUSIONS:
      Retroperitoneoscopic partial nephrectomy with transient occlusion of the renal
      artery is a useful and less-invasive method for resection of small renal tumors.
      Additional technologic developments to reduce ischemic times and to cool the
      kidneys laparoscopically are required.

PMID- 15245928
TI  - Utility of frozen section analysis of resection margins during partial
      nephrectomy.
AB  - OBJECTIVES: To evaluate the utility of routine intraoperative frozen-section
      histologic analysis during partial nephrectomy to ensure negative surgical
      margins. Partial nephrectomy has gained acceptance for surgical treatment of
      small renal cancers. Many surgeons send specimens for intraoperative frozen
      section histologic analysis to ensure negative margins. METHODS: We reviewed the
      records of 78 patients who underwent partial nephrectomy for presumed malignancy.
      Patient demographics, intraoperative findings, and pathologic and clinical
      outcomes were analyzed. RESULTS: Seventy-nine partial nephrectomies were
      performed in 78 patients. Frozen sections were obtained intraoperatively in 76
      cases. In 1 case (1.3%), a single margin was interpreted as positive for
      carcinoma, prompting deeper resection. The final histopathologic finding was
      interpreted as angiomyolipoma rather than carcinoma. The final pathologic
      examination revealed renal cell carcinoma in 52 (66%) of 79 cases. The mean
      oncologic follow-up was 16.2 months. One local recurrence was noted (1.9%). It
      arose in the resection bed 19 months after removal of a 4.5-cm tumor (pathologic
      Stage T3a). Both intraoperative frozen section margins and final pathologic
      margins were negative in this case. One patient developed pulmonary metastases
      and represented the only metastatic recurrence, as well as the only cancer
      related death in our cohort (1.9%). CONCLUSIONS: Our data suggest that when
      partial nephrectomy is performed with attention to excising a perimeter of
      grossly normal-appearing parenchyma, sending specimens for intraoperative frozen
      section analyses may provide an unnecessary expense without providing meaningful,
      reliable information. Additional studies, including larger cohorts and extended
      follow-up, are needed to support these results.

PMID- 15245929
TI  - Laparoscopic partial nephrectomy in patients with neoplasia in a solitary kidney.
AB  - OBJECTIVES: To assess the renal function and describe our operative experience
      with laparoscopic partial nephrectomy (LPN) in patients with solitary kidneys.
      METHODS: The medical records were analyzed to find patients with a solitary
      kidney and renal neoplasms who underwent LPN. Demographic, operative, pathologic,
      and follow-up data were obtained. RESULTS: Four patients were identified with
      solitary kidneys who had undergone LPN. The mean operative time was 251 minutes,
      mean warm ischemic time 15 minutes, mean estimated blood loss 395 mL, and mean
      hospitalization stay 3 days. The mean preoperative creatinine was 1.5 mg/dL and
      the mean peak creatinine 2.0 mg/dL. All patients returned to their baseline
      creatinine levels in the follow-up period. The final pathologic finding was Stage
      pT1 in 1, pT3a in 2, and angiomyolipoma in 1 patient. All surgical margins were
      negative. No cancer recurrence developed in the patients, with a mean follow-up
      of 17 months (range 3 to 35). CONCLUSIONS: LPN in patients with a solitary kidney
      is feasible and a reasonable treatment alternative to open partial nephrectomy.

PMID- 15245930
TI  - Elective open nephron-sparing surgery for renal masses: single-center experience
      with 129 consecutive patients.
AB  - OBJECTIVES: To present our experience with elective, open, nephron-sparing
      surgery for renal masses in a contemporary, consecutive series. METHODS: In this
      retrospective study, the files of all patients who underwent elective nephron
      sparing surgery between January 1996 and December 2002 at our institution were
      reviewed. The preoperative workup included renal ultrasonography and abdominal
      computed tomography. The histologic findings, complications, and oncologic
      outcome were studied. The surgical technique (ischemia and regional hypothermia)
      was identical in all patients. RESULTS: A total of 129 patients (mean age 61
      years) were analyzed. The mean +/- standard deviation tumor size on preoperative
      computed tomography was 4.0 +/- 2.4 cm. Renal cell carcinoma was present in 86
      patients (66.7%), a benign cyst in 18 (13.9%), oncocytoma in 10 (7.8%),
      angiomyolipoma in 7 (5.5%), adenoma in 4 (3.1%), xanthogranulomatous
      pyelonephritis in 3 (2.3%), and metastasis of a malignant melanoma in 1 patient.
      Two patients (1.6%) required secondary nephrectomy because of postoperative
      bleeding. After a median follow-up of 34 months (range 2 to 91), no patient had
      developed local recurrence, one (0.8%) had developed lymph node metastasis, and
      two (1.6%) had developed distant metastases. The creatinine clearance decreased
      from 77 +/- 27 mL/min before surgery to 64 +/- 23 mL/min after a median of 34
      months. CONCLUSIONS: The results of this contemporary, monocenter experience
      underline the role of open, elective, nephron-sparing surgery for patients with
      small renal masses, particularly because benign histologic findings were present
      in almost one third of patients.

PMID- 15245931
TI  - Kidney function after nephrectomy for renal cell carcinoma.
AB  - OBJECTIVES: To evaluate the function of the remaining kidney after nephrectomy
      for renal cell cancer by technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3)
      renal scintigraphy. METHODS: We evaluated 30 consecutive patients who were
      undergoing unilateral radical nephrectomy by 99mTc-MAG3 scintigraphy. All
      patients underwent three consecutive 99mTc-MAG3 scintigraphy studies. The first
      study was performed before nephrectomy, the second 1 month after surgery, and the
      third 1 year after surgery. At these times, the serum creatinine levels were also
      evaluated. RESULTS: The mean preoperative MAG3 clearance of the remaining kidney
      of the 30 patients was 155.4 mL/min/1.73 m2. The mean MAG3 clearance of the
      remaining kidney had increased to 209.2 mL/min/1.73 m2 by 1 month after
      nephrectomy, and the average percentage increase was 39.5%. After 1 year, it had
      increased to 211.3 mL/min/1.73 m2, with a 40.5% average percentage increase. The
      preoperative MAG3 clearance of the remaining kidney was inversely correlated with
      the percentage of increase in MAG3 clearance of the remaining kidney. Abnormal
      serum creatinine levels (greater than 1.3 mg/dL) were more common after
      nephrectomy, occurring in 6 patients at 1 month and in 5 patients at 1 year
      postoperatively. In all 6 patients with elevated creatinine levels, the
      preoperative MAG3 clearance of the remaining kidney was less than 150 mL/min/1.73
      m2. CONCLUSIONS: Adaptive hyperfunction occurs soon after nephrectomy that is not
      associated with age or sex and continues for at least 1 year. A greater
      compensatory response is produced in patients with more severe renal
      deterioration. Using 99mTc-MAG3 scintigraphy, we may be able to predict
      postoperative renal function.

PMID- 15245934
TI  - Conservative management of incidental contrast-enhancing renal masses as safe
      alternative to invasive therapy.
AB  - OBJECTIVES: To describe small contrast-enhancing renal masses suggestive of
      cancer that were managed conservatively with watchful waiting and serial computed
      tomography scans. Advanced diagnostic imaging has led to the increased incidental
      detection of renal masses in patients whose multiple comorbid conditions preclude
      invasive management. METHODS: A retrospective review was conducted of 29
      consecutive patients with 29 incidentally detected asymptomatic renal masses less
      than 3.5 cm in diameter that were managed conservatively with watchful waiting
      (because of patient wishes or multiple comorbid conditions) and serial computed
      tomography scans. RESULTS: The average patient age was 70 years (range 51 to 88),
      and the average duration of follow-up imaging was 32 months (range 10 to 89). The
      average number of follow-up computed tomography scans was 4.9 per patient (range
      1 to 11). The average width of the renal masses at diagnosis was 1.83 cm (range
      0.4 to 3.5), and the average change in size per year was 0.12 cm for all
      patients. Four patients underwent radical nephrectomy because of growth of the
      renal mass (n = 1) or patient wishes (n = 3). The histologic findings in 3 of
      these 4 patients were consistent with renal cell carcinoma. Two patients
      underwent radiofrequency ablation of the masses. At last follow-up, metastatic
      disease had not developed in any patient, and no patient had died of renal cell
      carcinoma. Two patients had died of other causes. CONCLUSIONS: The results of our
      study showed that when comorbid conditions or patient wishes preclude invasive
      treatment, contrast-enhancing renal masses less than 3.5 cm wide that are
      suggestive of cancer can be safely managed with watchful waiting and serial
      computed tomography scans.

PMID- 15245935
TI  - Foley versus intermittent self-catheterization after transvaginal sling surgery:
      which works best?
AB  - OBJECTIVES: To determine whether the duration of catheter use differed between
      subjects using clean intermittent self-catheterization and those using continuous
      Foley catheterization after transvaginal sling surgery. METHODS: We performed a
      retrospective analysis of postoperative bladder drainage in 167 consecutive women
      undergoing transvaginal suburethral sling placement for stress urinary
      incontinence. The primary outcome measure was the duration of catheter use.
      Normal voiding was defined as a voided volume equal to twice the residual volume
      and a residual volume of less than 100 mL for 24 hours. The groups were compared
      for differences in demographic, preoperative, and postoperative variables using
      univariate and multivariate analyses. The potential confounding effects of age,
      concomitant procedures, sling material, preoperative Valsalva voiding, and
      voiding pressures were investigated using general linear models. RESULTS: A total
      of 122 subjects used clean intermittent self-catheterization and 45 had Foley
      catheter drainage. No differences were found between the groups in terms of
      concomitant procedures performed and preoperative diagnoses. The median duration
      of catheter use was 12 days (range 1 to 120) for women using clean intermittent
      self-catheterization versus 8 days (range 1 to 120) for those using Foley
      catheter drainage (P = 0.026). This difference was not influenced by age,
      concomitant procedures, sling material, preoperative Valsalva voiding, or
      preoperative voiding pressures according to the multivariate analyses.
      CONCLUSIONS: Although many advocate bladder retraining for postoperative bladder
      rehabilitation, continuous bladder drainage may result in quicker recovery of
      normal voiding after sling procedures.

PMID- 15245936
TI  - New perineal bone-anchored male sling: lessons learned.
AB  - OBJECTIVES: To identify factors affecting outcome after the male sling procedure
      for stress urinary incontinence. METHODS: A total of 46 incontinent men, with a
      mean age of 67 years, underwent perineal bone-anchored male sling placement.
      Three titanium bone screws with preattached pairs of No. 1 polypropylene sutures
      were placed directly into the medial aspect of each inferior ramus of the pubic
      bone. To compress the urethra, three different types of materials were used:
      absorbable biomaterial, silicone-coated polypropylene mesh, or a composite graft.
      Patient characteristics, incontinence etiology and severity before surgery, prior
      collagen injections, and type of material used were assessed, and the association
      with the outcome of the male sling procedure was determined. RESULTS: The
      procedure was successful in 35 (76%) of 46 patients at a mean follow-up of 18
      months (range 6 to 30). Nineteen patients were totally dry and 16 had improved
      50% or more compared with before surgery. Failure occurred in 11 patients (24%).
      Patients who received a composite graft or mesh alone had a better outcome
      compared with the absorbable sling group (97% and 75% versus 0%, respectively, P
      = 0.001). The severity of pretreatment incontinence also had a negative impact on
      the outcome. CONCLUSIONS: Patients with mild-to-moderate incontinence and the use
      of a composite graft had the best outcomes after the perineal bone-anchored male
      sling.

PMID- 15245937
TI  - Improvement in depression and health-related quality of life after sacral nerve
      stimulation therapy for treatment of voiding dysfunction.
AB  - OBJECTIVES: To assess depression and health-related quality of life (HRQOL) in 89
      people with refractory urge incontinence, nonobstructive urinary retention, or
      urgency frequency enrolled at 13 U.S. study centers. The subjects were part of a
      large international, multicenter, randomized clinical trial on the safety and
      efficacy of sacral nerve stimulation for the treatment of refractory voiding
      dysfunction. METHODS: The Beck Depression Index and the Medical Outcomes Study
      Short-Form 36 were used to assess depression and HRQOL at baseline and at two
      follow-up visits. RESULTS: Detectable levels of depression and reduced quality of
      life were noted at baseline. Subjects implanted with the stimulation device
      reported significant improvements in both HRQOL and depression at 3 months after
      implant that were maintained for the 6-month study period. Subjects assigned to
      the delayed implant group showed a slight worsening of HRQOL and depression from
      baseline to 3 months that continued through the 6-month visit. CONCLUSIONS: The
      results demonstrated the serious impact that unresolved voiding symptoms have on
      the physical, social, and psychological dimensions of quality of life. Treating
      refractory voiding dysfunction with sacral nerve stimulation resulted in
      improvement in both depression and HRQOL.

PMID- 15245938
TI  - Prospective quality-of-life assessment in patients receiving concurrent
      gemcitabine and radiotherapy as a bladder preservation strategy.
AB  - OBJECTIVES: To assess, in a Phase I study, whether bladder preservation with
      concurrent gemcitabine and radiotherapy (RT) influenced patient-reported quality
      of life (QOL) as determined by the Functional Assessment of Cancer Therapy
      Bladder (FACT-BL). METHODS: Between January 1998 and March 2002, 24 patients with
      urothelial carcinoma of the bladder were enrolled, and 23 patients underwent
      transuretheral resection of bladder tumor, followed by twice-weekly gemcitabine
      with concurrent RT. The initial dose was 10 mg/m2 given twice weekly and
      increased as tolerated. To assess treatment-related QOL, patients completed the
      FACT-BL questionnaire. RESULTS: Of the 24 patients enrolled, 23 (96%) were
      assessed for toxicity and response. The FACT-generic (G) QOL assessment was
      obtained from 22 (92%) of 23 patients. No statistically significant difference
      was found in the FACT-G or FACT-BL or the combination before, during, or after
      treatment. The FACT-BL values were lower in patients who received higher doses of
      gemcitabine (greater than 20 mg/m2 versus 20 mg/m2 or less). At least one dose
      limiting toxicity (DLT) was experienced by 5 (23%) of 22 patients. The FACT-G
      values were lower for those patients who experienced DLT (difference of -13.1, P
      = 0.07). The physical well-being scores for patients who experienced DLT were
      lower after treatment (difference of -5.2, P = 0.03) compared with those without
      DLT. CONCLUSIONS: Concurrent RT and gemcitabine failed to statistically influence
      patient-reported QOL, although patients who received higher doses reported lower
      FACT-BL scores. The results of this study suggest that concurrent gemcitabine
      with conformal RT is a tolerable treatment regimen for bladder preservation, as
      demonstrated by the excellent treatment compliance and similar FACT measurements.

PMID- 15245940
TI  - Intermittent catheterization time required after interstitial laser coagulation
      of the prostate.
AB  - OBJECTIVES: To evaluate and minimize the duration of clean intermittent
      catheterization (CIC) required after interstitial laser coagulation of the
      prostate in patients with benign prostatic hyperplasia. METHODS: Patients who did
      not show sufficient improvement in lower urinary tract symptoms or voiding
      dysfunctions with alpha-1 adrenergic blockers, and who agreed to undergo
      interstitial laser coagulation of the prostate, were enrolled in this study.
      Postoperatively, the indwelling Foley catheters were removed by the next morning.
      Patients were then required to undertake CIC with alpha-1 adrenergic blockade
      therapy until the postvoid residual urine volume decreased to less than 100 mL.
      RESULTS: Seventy-nine patients underwent interstitial laser coagulation of the
      prostate, and 70 underwent catheter-free trials by postoperative day 1. The mean
      age and preoperative prostate volume of these 70 patients was 70.3 years (SD 8.7)
      and 49.6 cm3 (SD 34.8), respectively. Forty-three patients experienced
      postoperative urinary retention, and 37 of these underwent CIC. The median
      postoperative catheterization time was 3 days (range 0 to 31), and all patients
      eventually became catheter free. Univariate analysis showed that postoperative
      urinary retention was associated with a preoperative prostate volume of 30 cm3 or
      larger, a maximal flow rate of less than 6 mL/s, and a postvoid residual urine
      volume of 100 mL or greater. Multivariate analysis showed that a preoperative
      prostate volume of 30 cm3 or larger was the most significant predictor of
      postoperative urinary retention. CONCLUSIONS: More than 60% of the patients
      experienced urinary retention after interstitial laser coagulation of the
      prostate. However, the results of the present study suggested that CIC and alpha
      1 adrenergic blockade therapy could manage post-treatment urinary retention with
      a relatively short catheterization time.

PMID- 15245939
TI  - Polymorphism within the cyclin D1 gene is associated with an increased risk of
      carcinoma in situ in patients with superficial bladder cancer.
AB  - OBJECTIVES: To evaluate the prognostic value of CCND1 polymorphism in superficial
      and invasive transitional cell cancer of the bladder. METHODS: CCND1 polymorphism
      of blood DNA from patients with transitional cell cancer of the bladder was
      evaluated using the polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: No statistically significant difference was found
      in the recurrence-free survival of patients with superficial (pTa-T1)
      transitional cell cancer after transurethral resection among different genotype
      groups (AA versus GG, P = 0.746; GA versus GG, P = 0.979). In patients with
      superficial bladder cancer, the occurrence of primary carcinoma in situ was
      significantly greater in patients with the AA genotype compared with those with
      the GA or GG genotypes (P = 0.006, chi-square test). No statistically significant
      difference was found in disease-specific survival after radical cystectomy among
      the different genotype subgroups (AA versus GG, P = 0.245; GA versus GG, P =
      0.649). CONCLUSIONS: Although CCND1 polymorphism is not able to serve as a
      prognostic marker for bladder cancer, the CCND1 variant A allele may recessively
      increase the risk of carcinoma in situ incidence in patients with superficial
      bladder cancer.

PMID- 15245941
TI  - Long-term outcome of patients with prostate cancer and pathologic seminal vesicle
      invasion (pT3b): effect of adjuvant radiotherapy.
AB  - OBJECTIVES: To evaluate the long-term outcome of patients with prostate cancer
      who have pathologic seminal vesicle invasion without lymph node metastasis
      (pT3bN0M0) and compare management strategies. METHODS: From October 1987 to
      August of 1997, 43 men underwent radical prostatectomy at Thomas Jefferson
      University Hospital, had pT3bN0M0 disease, complete preoperative and
      postoperative prostate-specific antigen (PSA) data, and a minimum of 2 years of
      follow-up. Eighteen patients with undetectable postoperative PSA levels received
      adjuvant radiotherapy (RT) within 6 months of surgery. Twelve patients with
      undetectable PSA levels postoperatively were considered for salvage treatment at
      biochemical progression. Thirteen patients with persistently elevated PSA levels
      postoperatively underwent immediate salvage RT. We evaluated the prognostic
      factors for freedom from biochemical failure (bNED), distant metastasis (DM),
      disease-specific survival, and overall survival. RESULTS: The median follow-up
      time was 5.9 years (range 2 to 10). Patients who received adjuvant RT had
      significantly greater 5-year bNED survival than patients who did not (80% versus
      8%, P <0.001) and increased freedom from DM that was of borderline significance
      (P = 0.05). The 5-year survival estimates for DM were 0% for the adjuvant RT
      versus 17% for the observed patient group. In patients with undetectable
      postoperative PSA levels, the preoperative PSA level was an independent
      prognostic factor for later disease progression. Patients with a preoperative PSA
      level of less than 20 ng/mL showed significantly greater 5-year bNED survival
      than those with a preoperative PSA level of 20 ng/mL or greater (56% versus 32%,
      P <0.05). The survival curves for risk of DM and death from prostate cancer for
      those two patient groups were not significantly different statistically.
      CONCLUSIONS: Although pathologic seminal vesicle invasion has been associated
      with poor prognosis and high DM risk, adjuvant RT may result in improved bNED
      survival in patients with undetectable PSA levels after radical prostatectomy.
      The effect on clinical outcome awaits additional follow-up.

PMID- 15245942
TI  - Five-year outcomes after neoadjuvant chemotherapy and conformal radiotherapy in
      patients with high-risk localized prostate cancer.
AB  - OBJECTIVES: To describe the 5-year outcomes of patients with high-risk localized
      prostate cancer treated with neoadjuvant estramustine and vinblastine followed by
      concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT).
      METHODS: A total of 23 patients completed therapy consisting of two 8-week cycles
      of vinblastine, weekly as 4 mg/m2, followed by 8 weeks of concomitant
      chemotherapy and 3D-CRT. Estramustine was given daily at 10 mg/kg in three
      divided doses. 3D-CRT consisted of a total dose of 7560 cGy. RESULTS: Assessable
      patients include 9 with Stage T3 or greater tumors and 5 with lymph node
      metastasis at diagnosis. All patients had a Gleason score 7 or greater. The
      median follow-up was 60 months. Of the 23 assessable patients, 15 (65%)
      experienced biochemical relapse by American Society for Therapeutic Radiology
      Oncology criteria. The median time to prostate-specific antigen relapse was 12
      months (range 7 to 16). Five patients (22%) developed metastases. The median time
      to metastasis had not been reached by last follow-up. Of the 23 assessable
      patients, 11 (48%) received no additional therapy and had noncastrate
      testosterone levels. Six patients had no evidence of disease and 9 patients were
      receiving androgen blockade. Three patients died (one of prostate cancer and two
      of other diseases). CONCLUSIONS: A substantial proportion of patients with
      unfavorable-risk localized prostate cancer achieved long-term disease control
      with estramustine and vinblastine and concurrent 3D-CRT, no significant long-term
      toxicities were seen and 48% underwent no further therapy after RT. These long
      term findings support the continued study of chemotherapy combined with RT as a
      potential alternative to prolonged androgen deprivation.

PMID- 15245943
TI  - General versus spinal anesthesia in patients undergoing radical retropubic
      prostatectomy: results of a prospective, randomized study.
AB  - OBJECTIVES: To evaluate the impact of general anesthesia (GA) versus spinal
      anesthesia (SpA) on intraoperative and postoperative outcome in patients
      undergoing radical retropubic prostatectomy. METHODS: Seventy-two consecutive
      patients with clinically localized prostate cancer were randomized into group 1
      (GA: 34 patients) or group 2 (L2-L3 or L3-L4 SpA: 38 patients) and underwent
      radical retropubic prostatectomy. The intraoperative and postoperative anesthetic
      and surgical variables were evaluated. RESULTS: The mean +/- SEM operative time
      was not significantly different between the two groups (P = 0.43). The overall
      blood loss was less in group 2 (P = 0.04). The mean +/- SEM postoperative time in
      the postoperative holding area was significantly shorter after SpA than after GA
      (P <0.0001). The perioperative pain outcome in the postoperative holding area was
      significantly better for group 2 than for group 1 (P = 0.0017), but postoperative
      pain on day 1 was not significantly different between the two groups. The
      postoperative sedation score was significantly less in group 2 than in group 1 (P
      <0.0001). On day 1, first flatus passed in a significantly larger number of
      patients in group 2 (P <0.0001), and the overall gait was greater for group 2
      patients (P = 0.02). CONCLUSIONS: These results suggest that SpA allows good
      muscle relaxation and a successful surgical outcome in patients undergoing
      radical retropubic prostatectomy with pelvic lymphadenectomy for clinically
      localized prostate cancer. Moreover, SpA results in less intraoperative blood
      loss, less postoperative pain, and a faster postoperative recovery than GA.

PMID- 15245944
TI  - Endorectal MRI for prediction of tumor site, tumor size, and local extension of
      prostate cancer.
AB  - OBJECTIVES: To assess the value of endorectal magnetic resonance imaging (MRI)
      for detecting the tumor site, tumor size, and disease extent in patients with
      localized prostate cancer. METHODS: The MRI findings were compared with the
      histopathologic findings of radical prostatectomy specimens in 95 patients.
      RESULTS: The histologic examination revealed 186 cancer foci. Endorectal MRI
      detected 109 cancer foci. The accuracy, sensitivity, and positive predictive
      value of endorectal MRI for detecting tumor foci greater than 1.0 cm in diameter
      was 79.8%, 85.3%, and 92.6%, respectively; the corresponding value for detecting
      tumor foci smaller than 1.0 cm was 24.2%, 26.2%, and 75.9%, respectively. The
      maximal tumor diameter on endorectal MRI correlated with that shown by histologic
      examination for tumors larger than 1.0 cm in diameter. However, it did not
      correlate significantly with the histologic diameter of tumors smaller than 1.0
      cm. The accuracy, sensitivity, specificity, positive predictive value, and
      negative predictive value of endorectal MRI was 74.7%, 57.1%, 82.1%, 57.1%, and
      82.1%, respectively, for the detection of extracapsular extension and was 75.8%,
      62.1%, 81.8%, 60.0%, and 83.1%, respectively, for local staging. CONCLUSIONS: The
      results of the present study suggest that endorectal MRI is useful for predicting
      local extension, as well as tumor site and tumor size, of cancer foci greater
      than 1.0 cm in diameter.

PMID- 15245945
TI  - Verification and incorporation biases in studies assessing screening tests:
      prostate-specific antigen as an example.
AB  - OBJECTIVES: Prostate-specific antigen (PSA) measurement is a widely used
      screening test for prostate cancer. However, studies assessing the performance of
      PSA suffer from verification bias and incorporation bias, because men with PSA
      levels less than 4 ng/mL do not undergo biopsy unless the digital rectal
      examination findings are suspicious for prostate cancer. We have reviewed how
      these biases have influenced such studies. METHODS: We compared the results of
      three studies that reported on the test characteristics of PSA, taking into
      account the types of bias present. We applied approximate verification bias
      corrections to previously reported age-specific reference ranges, based on the
      reported 22% cancer detection rate in the PSA range 2.5 to 4 ng/mL. To adjust for
      incorporation bias, we removed PSA from the criteria establishing the absence of
      prostate cancer and recalculated the test characteristics of PSA. RESULTS:
      Verification bias led to an elevation in the sensitivity estimates of PSA. The
      specificity increased or decreased depending on the type of bias present. After
      accounting for incorporation bias, the sensitivity of PSA testing at a 4-ng/mL
      cutoff level was less than 67%, and the specificity was more than 80.6%.
      CONCLUSIONS: Studies evaluating PSA testing have been biased because of the
      presence of verification and incorporation biases. Future studies must consider
      the possibility of these biases to obtain valid results.

PMID- 15245946
TI  - Searching the Internet for information on prostate cancer screening: an
      assessment of quality.
AB  - OBJECTIVES: To identify how on-line information relating to prostate cancer
      screening (PCS) is best sourced, whether through general, medical, or meta-search
      engines, and to assess the quality of that information. METHODS: Websites
      providing information about PCS were searched across 15 search engines
      representing three distinct types: general, medical, and meta-search engines. The
      quality of on-line information was assessed using the DISCERN quality assessment
      tool. Quality performance characteristics were analyzed by performing Mann
      Whitney U tests. Search engine efficiency was measured by each search query as a
      percentage of the relevant websites included for analysis from the total returned
      and analyzed by performing Kruskal-Wallis analysis of variance. RESULTS: Of 6690
      websites reviewed, 84 unique websites were identified as providing information
      relevant to PCS. General and meta-search engines were significantly more
      efficient at retrieving relevant information on PCS compared with medical search
      engines. The quality of information was variable, with most of a poor standard.
      Websites that provided referral links to other resources and a citation of
      evidence provided a significantly better quality of information. In contrast,
      websites offering a direct service were more likely to provide a significantly
      poorer quality of information. CONCLUSIONS: The current lack of a clear consensus
      on guidelines and recommendation in published data is also reflected by the
      variable quality of information found on-line. Specialized medical search engines
      were no more likely to retrieve relevant, high-quality information than general
      or meta-search engines.

PMID- 15245947
TI  - Patient, surgeon, and treatment characteristics associated with homologous blood
      transfusion requirement during radical retropubic prostatectomy: multivariate
      nomogram to assist patient counseling.
AB  - OBJECTIVES: To identify the preoperative patient, treatment, and surgeon factors
      associated with the administration of homologous blood transfusion during or
      after radical retropubic prostatectomy (RRP) to be able to better inform patients
      regarding the probability of transfusion. Homologous blood transfusion is
      sometimes required during or after RRP, but predictive models for estimating
      transfusion probability using patient and surgical characteristics are lacking.
      METHODS: Data were prospectively collected regarding patient characteristics,
      cancer severity, surgeon experience, anesthetic used, operative blood loss, and
      transfusion among 1123 consecutive RRP cases. Multivariate regression analysis
      identified baseline factors associated with a homologous transfusion requirement
      and generated a model for predicting the likelihood of perioperative homologous
      transfusion. RESULTS: Homologous transfusion was administered in 3.8% of
      subjects; the mean estimated blood loss was 953 mL. Multivariable regression
      analysis identified prostate size (P <0.0001, odds ratio [OR] 1.74), use of
      general anesthesia (P = 0.01, OR 2.22), use of neoadjuvant hormonal therapy (P =
      0.006, OR 3.35), and surgeon expertise (P <0.0001, OR 8.63) as independent risk
      factors associated with a need for perioperative homologous transfusion. The most
      influential factor, surgical expertise, clustered among surgeons who performed
      more than 15 RRPs annually, because these surgeons had lower transfusion rates
      and lower estimated blood loss more consistently than did surgeons who performed
      fewer RRPs annually. CONCLUSIONS: Larger prostate size, use of general
      anesthesia, use of neoadjuvant hormonal therapy, and annual surgeon case volume
      were independently associated with an increased probability that an individual
      patient would receive homologous transfusion during or after RRP. A nomogram
      indicating the probability of homologous transfusion based on these factors
      provides a benchmark of expected homologous transfusion rates according to
      individual patient and treatment parameters.

PMID- 15245948
TI  - Nerve-sparing laparoscopic radical prostatectomy: replicating the open surgical
      technique.
AB  - OBJECTIVES: To present a detailed demonstration of a nerve-sparing laparoscopic
      radical prostatectomy (LRP) technique that replicates anatomic nerve-sparing
      radical retropubic prostatectomy (RRP). Techniques for neurovascular bundle
      preservation during open RRP have undergone several decades of careful
      refinement. Identifying pre-existing anatomic planes and the avoidance of thermal
      injury near the nerves are principles considered paramount during nerve-sparing
      RRP. During LRP and robotic-assisted radical prostatectomy, the use of cautery
      for hemostasis during nerve dissection is common despite its unknown effects on
      cavernous nerve function. METHODS: We describe a combined antegrade and
      retrograde laparoscopic approach to neurovascular bundle dissection. The
      technique is demonstrated in the accompanying video segments. The use of
      specialized laparoscopic instrumentation, including a fine-tipped right-angle
      clamp and curved dissector, is discussed. The principles of meticulous tissue
      handling and avoidance of electrocautery are stressed. The preliminary outcomes
      are presented using data obtained using an abridged version of the International
      Index of Erectile Function and the Expanded Prostate Cancer Index Composite
      questionnaires. RESULTS: To date, our technique has been applied to LRP in more
      than 177 patients. Blood loss has been minimal (less than 300 mL), and
      intraoperative anatomic nerve preservation appeared excellent. On the basis of
      our early experience, 76% of patients engaging in sexual intercourse
      preoperatively who underwent bilateral nerve preservation (n = 21) reported the
      ability to engage in sexual intercourse 1 year after LRP. CONCLUSIONS: Our nerve
      sparing LRP technique replicates established open surgical principles of anatomic
      nerve-sparing RRP. The techniques described here minimize the potential for
      cavernous nerve damage from electrical energy or heat. Early functional outcomes
      appear comparable to the results obtained with open RRP performed at our
      institution.

PMID- 15245949
TI  - Effects of gonadotropin-releasing hormone agonists on bone metabolism markers and
      bone mineral density in patients with prostate cancer.
AB  - OBJECTIVES: To better understand bone metabolism and predict bone loss in
      treatment using gonadotropin-releasing hormone agonist for patients with prostate
      cancer. METHODS: The changes in bone mineral density and blood levels of bone
      metabolism markers and the level of pyridinoline cross-linked carboxy-terminal
      telopeptide of type I collagen, a specific marker of bone resorption, and carboxy
      terminal pro-peptide of human type I procollagen, a specific marker of bone
      formation, were examined in 27 consecutive patients with prostate cancer without
      bone metastasis. RESULTS: After 2 years of gonadotropin-releasing hormone
      treatment, the bone mineral density was significantly lower (median 0.937 g/cm2)
      than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of
      type I collagen began to increase significantly 6 months after the start of
      treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL,
      median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I
      procollagen began to show a significant rise 1 year after the start of treatment
      (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL,
      median 132.0, at 1 year). CONCLUSIONS: Functional coupling between bone
      resorption and formation was noted, and a decrease in bone mass, even in men,
      owing to androgen deficiency, was biochemically demonstrated. Fluctuations in
      these two bone metabolism markers preceded the decrease of bone mineral density.
      Therefore, these markers might be a predictor of bone loss.

PMID- 15245950
TI  - Association of lower urinary tract symptoms with erectile dysfunction in Japanese
      men.
AB  - OBJECTIVES: To assess the age-stratified prevalence of erectile dysfunction (ED)
      and how lower urinary tract symptoms (LUTS) are associated with ED, and to
      estimate the correlates of ED among Japanese men. METHODS: A self-administered
      questionnaire of the International Prostate Symptom Score and the abridged 5-item
      version of the International Index of Erectile Function were given to 3189
      noninstitutionalized men during a multiphasic health screening. The data from
      2084 men who provided complete responses to the questionnaire were analyzed.
      RESULTS: The prevalence of moderate to severe ED increased from 13.4% among those
      younger than 40 years to 20.6%, 39.9%, and 63.1% among those aged 40 to 49, 50 to
      59, and 60 years or older, respectively. Most were dissatisfied with their sex
      life regardless of age. The severity of ED was significantly associated with
      moderate to severe International Prostate Symptom Scores (age-adjusted odds ratio
      1.52), specifically in the urgency (1.75) and nocturia (1.36) domains, and for
      those with diabetes mellitus (2.54) and coronary artery disease (8.04).
      CONCLUSIONS: ED is highly prevalent among Japanese men with LUTS and is
      significantly associated with the severity of LUTS after controlling for age.
      This significant aspect of life for men of all ages should be taken into account
      when treating patients with LUTS.

PMID- 15245951
TI  - Does varicocele grade predict vein number and size at microsurgical subinguinal
      repair?
AB  - OBJECTIVES: To correlate the varicocele grade on physical examination with the
      number and size of the veins present and ligated during surgery. Varicoceles are
      correctable causes of male factor infertility. No prior anatomic studies have
      correlated the preoperative clinical grade of a varicocele with the number of
      veins discovered and ligated during microsurgical subinguinal repair. METHODS: A
      total of 65 consecutive men (mean age 33.8 years) diagnosed during office
      evaluation with either unilateral left varicocele or bilateral varicoceles
      underwent microsurgical subinguinal varicocelectomy by one urologist. At surgery,
      the number and size (small, less than 1.0 mm; medium, 1.0 mm or greater to less
      than 4.0 mm; large, 4.0 mm or greater) of the spermatic cord veins present and
      ligated were recorded. These findings were correlated with the size of the
      preoperative varicocele grade. RESULTS: Of the 71 varicocele units, 65 qualified
      for analysis. Of the patients with a grade 1 varicocele, a mean (+/-SD) of 2.4
      (+/-2.5) small veins, 4.7 (+/-2.1) medium veins, 0.3 (+/-0.58) large veins, and
      7.5 (+/-3.0) total veins were ligated. Of patients with a grade 2 varicocele, a
      mean of 2.6 (+/-2.3) small veins, 5.3 (+/-3.1) medium veins, 0.47 (+/-0.78) large
      veins, and 8.3 (+/-3.2) total veins were ligated. Of patients with grade 3
      varicoceles, a mean of 1.8 (+/-1.8) small veins, 4.6 (+/-2.3) medium veins, 1.0
      (+/-0.75) large veins, and 6.9 (+/-2.6) total veins were ligated. Using analysis
      of variance, the grade 3 varicoceles had significantly more large veins than did
      grade 1 varicoceles (P <0.05). CONCLUSIONS: Grade 3 varicoceles have a greater
      number of large veins compared with grade 1 varicoceles.

PMID- 15245952
TI  - Urachal inflammatory myofibroblastic tumor with ALK gene rearrangement: a study
      of urachal remnants.
AB  - OBJECTIVES: Abnormalities of the urachus are rare among children and include a
      patent tract and cyst formation. These structures can also be affected by
      infection and abscess development. They are usually diagnosed during infancy and
      treated by surgical resection. Involvement of this remnant by either benign or
      malignant tumors is very infrequent. A few cases of mesenchymal tumors, such as
      desmoid tumor and leiomyoma, involving the urachus have been described in
      published reports. METHODS: We studied an inflammatory myofibroblastic tumor
      arising from the urachus in a 10-year-old boy. In addition, we reviewed 101 cases
      of urachal remnants retrieved from the surgical pathology and autopsy files in
      the Department of Pathology at the Children's Hospital Boston diagnosed in the
      past 82 years. RESULTS: The urachal inflammatory myofibroblastic tumor showed
      anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and
      fluorescence in situ hybridization techniques. No other neoplasms were diagnosed
      in the analyzed population. CONCLUSIONS: We describe an example of inflammatory
      myofibroblastic tumor involving the urachus. Involvement of the urachus by tumors
      is rare, but these should be considered in the differential diagnosis of urachal
      lesions.

PMID- 15245953
TI  - Laparoscopic sacral colpoperineopexy for treatment of perineal body descent and
      vaginal vault prolapse.
AB  - Perineal body descent has been linked to pudendal nerve injury and anorectal
      disorders, including constipation, rectal pain, and fecal incontinence. Open
      sacral colpoperineopexy has been described for the treatment of perineal descent.
      We present a technique for laparoscopic sacral colpoperineopexy and highlight
      this approach with accompanying video segments.

PMID- 15245954
TI  - Preservation of accessory pudendal arteries during radical retropubic
      prostatectomy: surgical technique and results.
AB  - INTRODUCTION: Our institution previously described a surgical technique for
      preservation of accessory pudendal arteries at radical retropubic prostatectomy.
      Since then, we have expanded our experience. We now report our refinements in the
      surgical technique, illustrated with video, and the influence of accessory artery
      preservation on the recovery of sexual function after radical retropubic
      prostatectomy (RRP). TECHNICAL CONSIDERATIONS: Between 1987 and 2003, 2399 potent
      men underwent RRP. Of the 2399 men, 84 (4%) were identified with accessory
      pudendal arteries. Of the 84 men, 52, who underwent bilateral nerve-sparing
      surgery, were available for evaluation. We identified a control population,
      without accessory pudendal arteries, who were matched for age, stage, and
      neurovascular bundle status. Potency was defined as the ability to achieve
      unassisted intercourse with or without the use of sildenafil. In a Cox
      proportional hazards model, the effect of artery preservation increased the
      likelihood of potency more than twofold (relative risk 2.65; 95% confidence
      interval 1.11 to 6.32; P = 0.028). Kaplan-Meier analysis showed a significantly
      shorter median time to regain potency among those with artery preservation, 6
      versus 12 months (P = 0.020). CONCLUSIONS: Preservation of accessory pudendal
      arteries may favorably influence the recovery of sexual function and interval to
      recovery after RRP.

PMID- 15245955
TI  - Renal cell carcinoma in cross renal ectopia with fusion: diagnosis and operative
      planning by multidetector three-dimensional computed tomography.

PMID- 15245956
TI  - Retroperitoneal liposarcoma and aldosteronoma.

PMID- 15245957
TI  - Acute renal failure resulting from huge inguinal bladder hernia.
AB  - We report a case of a huge inguinal/scrotal bladder hernia presenting as acute
      renal failure. A 66-year-old man with a large scrotal mass presented with
      metabolic acidosis and azotemia and was admitted to the intensive care unit.
      Computed tomography displayed the bladder completely herniated into the scrotum
      and bilateral hydronephrosis. After stabilization and percutaneous nephrostomy
      placement, the patient's creatinine markedly improved, and the hernia was
      repaired. Bilateral ureteral obstruction from a bladder hernia is a very rare
      event. Computed tomography is rapid and helpful in this situation. Hernia repair
      can safely be performed after nephrostomy drainage.

PMID- 15245958
TI  - Three-chamber priapism in a patient with primary epithelioid hemangioendothelioma
      of penis.
AB  - A 58-year-old man presented with a 6-month history of painful progressive penile
      firmness, initially diagnosed as Peyronie's disease. Penile fibrosis involved the
      entire corpora cavernosa and spongiosum, making it consistent with three-chamber
      priapism. Cavernosal biopsies revealed epithelioid hemangioendothelioma, and the
      metastatic workup found hepatic and pulmonary lesions. The patient was treated
      with paclitaxel, but eventually died of cancer progression. Early infiltrative
      vascular malignancies of the penis may be indistinguishable from Peyronie's
      disease. A review of published reports revealed that penile masses associated
      with progressive growth, obstructive urinary symptoms, dysuria, or painful
      erections might warrant further evaluation with biopsies.

PMID- 15245959
TI  - Plasma cell infiltration of the urinary bladder.
AB  - We report a novel entity of plasma cell bladder infiltration without other
      demonstrable disease. The patient had severe irritative voiding symptoms,
      hematuria, and a diffuse mucosal infiltrate with 90% plasma cells. Although the
      patient demonstrated some clinical and pathologic evidence consistent with
      interstitial cystitis and eosinophilic cystitis, a predominant finding of focal
      plasma cell infiltration of the urinary bladder suggests a new or previously
      unrecognized clinical entity.

PMID- 15245960
TI  - Metastatic Merkel cell tumor to the prostate and bladder.
AB  - Merkel cell carcinoma is an uncommon cutaneous neoplasm of neuroendocrine origin.
      We report the case of a 71-year-old man with Merkel cell carcinoma metastases to
      the prostate and bladder presenting with lower urinary tract obstruction. Efforts
      should be made to optimize the patient's quality of life with the finding of
      metastatic Merkel cell carcinoma to the bladder or prostate until better adjuvant
      therapies are identified.

PMID- 15245961
TI  - Tuberculous epididymitis with extensive retroperitoneal and mediastinal
      involvement.
AB  - The incidence of tuberculosis in the United States is on the rise, in part,
      because of its association with acquired immunodeficiency syndrome. Genitourinary
      tuberculosis remains one of the most common forms of secondary or extrapulmonary
      disease. We present an unusual case of tuberculous epididymitis with extensive
      retroperitoneal and mediastinal spread. The possible routes of dissemination, as
      well as the efficacy of antimycobacterial therapy in the management of
      tuberculous epididymitis, are discussed and the relevant literature is reviewed.

PMID- 15245962
TI  - Quantitative detection of cytokeratin 20 mRNA expression in bladder carcinoma by
      real-time reverse transcriptase-polymerase chain reaction.
AB  - OBJECTIVES: To determine cytokeratin 20 (CK 20) expression in tumor tissue,
      normal urothelial tissue, bladder washings, and urine from patients with
      urothelial carcinoma by real-time reverse transcriptase-polymerase chain reaction
      using the LightCycler Instrument. METHODS: Urine, bladder washings, tumor, and
      normal urothelial tissue were obtained from 33 patients with bladder carcinoma.
      RNA was subsequently extracted. Twenty tissue samples from healthy volunteers
      were used as controls. Real-time reverse transcriptase-polymerase chain reaction
      with the LightCycler was performed using fluorescence-labeled CK 20 primers as
      the target gene and the porphobilinogen deaminase housekeeping gene as the
      internal standard. RESULTS: CK 20 mRNA expression was detected in all samples
      investigated. CK 20 expression in the tissue and urine samples from patients with
      tumor was significantly increased compared with that in normal urothelial tissue
      (P = 0.028) or urine from the negative control group (P = 0.012). The average CK
      20 expression was 70,140 arbitrary units (AU) in tumor tissue (30,533 AU in urine
      from patients with tumor) and 8460 AU in normal urothelial tissue (2234 AU in
      normal urine). A stage-related difference in CK 20 mRNA expression was observed
      in tumor tissue (P = 0.027) and for tumor grade G1-G2 versus G3 (P = 0.03).
      CONCLUSIONS: CK 20 mRNA expression levels in tissue and urine were elevated in
      patients with urothelial carcinoma compared with the levels in healthy
      individuals. CK 20 expression was also detectable in normal urine or normal
      urothelial tissue, but at significantly lower levels than in tumor samples.
      Fluorescence-labeled quantitative polymerase chain reaction using the LightCycler
      helped to differentiate between low-level CK 20 expression in normal urothelial
      tissue and the levels in tumor tissue samples. CK 20 might be an excellent and
      sensitive marker for tumor monitoring and routine follow-up in patients with
      transitional cell carcinoma.

PMID- 15245963
TI  - Differential expression of activator protein-2 isoforms in renal cell carcinoma.
AB  - OBJECTIVES: To investigate the expression of activator protein-2 (AP-2) in renal
      cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha),
      beta (beta), and gamma (gamma) are known to exhibit a highly homologous
      structure; however, their functions are considered to be different. AP-2 has been
      implicated to play a role in carcinogenesis, as well as in the development of the
      kidney. METHODS: The expression of the three AP-2 isoforms, alpha, beta, and
      gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal
      growth factor receptor and erbB2 expression in 42 patients with RCC was also
      evaluated to investigate the correlation with AP-2 isoforms. RESULTS: AP-2
      isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue
      specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP
      2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression
      than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of
      the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably,
      localized small cases had a significantly greater rate of nuclear staining for AP
      2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2
      cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor
      receptor and erbB2 expression did not correlate with expression of the AP-2
      isoforms. CONCLUSIONS: AP-2 isoforms were differentially expressed in RCC, as
      well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear
      cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and
      this transcription factor may be related to early carcinogenesis.

PMID- 15245965
TI  - Enhanced renal parenchymal cryoablation with novel 17-gauge cryoprobes.
AB  - OBJECTIVES: To evaluate novel, 17-gauge cryoprobes with a modified heat exchange
      mechanism to evaluate the area of ablation that could be achieved with 17-gauge
      (1.47-mm) cryoprobes. METHODS: Eleven pigs were divided into four groups. Each
      animal underwent laparoscopic creation of three cryolesions with an ellipical
      iceball-generating 17-gauge cryoprobe (group 1), one that generates a teardrop
      shaped iceball (group 2), a template of three standard 17-gauge cryoprobes (group
      3), or a single, standard, large-caliber (3.4-mm) cryoprobe (group 4). Each
      cryolesion was created with a standard double-freeze cycle. Intraoperative
      ultrasonography was used to measure the maximal iceball dimensions, and the renal
      temperatures were measured with a thermocouple. The animals were killed after 14
      days. The gross lesion size and histopathologic area of necrosis were documented.
      RESULTS: The mean temperature for the surrounding renal parenchyma was not
      significantly different among the groups. No statistically significant difference
      was noted in the size of the gross or histopathologic lesions created among the
      four groups. The gross lesion size correlated statistically significantly with
      the histologic area of necrosis (P <0.01). CONCLUSIONS: Despite the diminutive
      size of the 17-gauge cryoprobes tested, the probes ablated tissue volumes
      equivalent to that ablated using the larger, standard 3.4-mm cryoprobe or a
      configuration of three standard 17-gauge cryoprobes. These novel 17-gauge
      cryoprobes may facilitate ablation of small and medium-size renal tumors and may
      have expanded application for percutaneous ablation owing to the decreased risk
      of hemorrhage.

PMID- 15245964
TI  - Inhibitory effect of the antidepressant St. John's wort (hypericum perforatum) on
      rat bladder contractility in vitro.
AB  - OBJECTIVES: To evaluate the effect of St. John's wort (SJW), an effective and
      safe herbal antidepressant, on rat bladder contractility. Recent data have
      suggested a strong association between depression and urinary incontinence.
      METHODS: Strips were cut from the bladder body and placed in organ baths
      containing Krebs solution. Contractions were induced by electrical field
      stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)
      methylene adenosine triphosphate. RESULTS: St. John's wort was significantly more
      active in inhibiting the EFS-induced contractions than the alpha,beta-methylene
      adenosine triphosphate-induced contractions, suggesting both a presynaptic site
      of action and a direct inhibition of bladder smooth muscle. The inhibitory effect
      of SJW on EFS-induced contractions was unaffected by methysergide, haloperidol,
      phentolamine plus propranolol (antagonists that block the action of the
      neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own
      receptors), the L-type calcium channel antagonist verapamil, capsazepine (which
      blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A.
      However, the opioid receptor antagonist naloxone significantly reduced the
      inhibitory effect of SJW on EFS-induced contractions. Among the chemical
      constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid
      kaempferol showed inhibitory effects. CONCLUSIONS: The results of our study
      demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder
      and also directly inhibits smooth muscle contractility. The inhibitory effect on
      excitatory transmission could involve, at least in part, opioid receptors. SJW
      may be evaluated for its possible use in treating urinary incontinence in
      depressed patients.

PMID- 15245966
TI  - Positive correlation between allelic loss at chromosome 14q24-31 and poor
      prognosis of patients with renal cell carcinoma.
AB  - OBJECTIVES: To report our development of a new application of the inter-Alu long
      polymerase chain reaction (PCR) for genomic scanning to screen for tumor-specific
      alterations in tumor DNA. Using this method, we detected a rearranged chromosomal
      region in renal cell carcinomas (RCCs). We then examined tumor-specific allelic
      loss in this region using microsatellite markers and determined whether a
      relationship was present between this allelic loss and the clinicopathologic
      features of the patients. METHODS: The inter-Alu long PCR genomic scan method was
      performed using RCC DNA samples and primers specific for a minor subset of the
      human repeat sequence Alu. We analyzed DNA samples from 42 pairs of matched
      normal and nonpapillary RCC tissues with seven microsatellite markers. RESULTS:
      The inter-Alu long PCR genomic scan method revealed an altered DNA region on
      chromosome 14q24-31, which is the location of several putative tumor suppressor
      genes. At least one of seven microsatellite markers on chromosome 14q24-31 showed
      loss of heterozygosity in 23 (54.8%) of 42 informative cases of RCC. The
      prevalent loss region was confined to a 2-Mb region around D14S67. We found a
      positive correlation between the presence of the loss of heterozygosity on 14q24
      31 and tumor stage (P <0.05). We also found that cases with allelic loss at 14q24
      31 had a poor prognosis (P = 0.045). CONCLUSIONS: Our inter-Alu long PCR genomic
      scan method is a powerful method for the screening of DNA alterations, and our
      data suggest that the chromosome 14q24-31 region contains likely tumor suppressor
      genes associated with the progression of RCC.

PMID- 15245967
TI  - "On the physiology of micturition" by Denny-Brown and Robertson: a classic paper
      revisited.

PMID- 15245968
TI  - Anesthesia for prostate biopsy.

PMID- 15245969
TI  - Prostate cancer cells: detection and isolation from peripheral blood and bone
      marrow.

PMID- 15245970
TI  - Suprapubic stab cystostomy.

PMID- 15245972
TI  - High-grade urinary bladder leiomyosarcoma in adults.

PMID- 15245975
TI  - Whitmoreisms.

PMID- 15245973
TI  - Fascia lata graft for urethral fistula repair.

PMID- 15245976
TI  - Continued undertreatment of older men with localized prostate cancer.

PMID- 15245979
TI  - Chlorophyll a and its derivatives in sediments of the Odra estuary as a measure
      of its eutrophication.
AB  - Chlorophyll a and its selected derivatives, as well as chlorophylls b and c have
      been determined in samples of recent (0-10 cm) sediments, collected at 30
      stations in the Szczecin Lagoon, Pomeranian Bay and the Bornholm Deep. Samples
      were retrieved in different seasons between 1992 and 2001, including the time
      before and after the great flood of July 1997. Regarding the content of
      chlorophyll a and its derivatives in sediments, the Szczecin Lagoon may be
      classified as permanently eutrophic and the Pomeranian Bay and Bornholm Deep as
      mesotrophic. A lack of correlation between chlorophylls b, c and chlorophyll a
      indicated that intensive blooms of cyanobacteria occur in the Szczecin Lagoon,
      which is a characteristic of eutrophic zones. The chlorin a results are related
      to selected parameters characterizing the aquatic environment. The values for
      nutrients, salinity and temperature in near-bottom waters, as well as
      granulometry and organic carbon in the sediments verify the above conclusions.

PMID- 15245980
TI  - Sediment disturbance off the Tagus Estuary, Western Portugal: chronic
      contamination, sewage outfall operation and runoff events.
AB  - Sediment disturbance patterns in the coastal area off the Tagus Estuary
      (Portugal) have been assessed using a set of combined techniques. The potential
      sources of disturbance in the area include chronic contamination of the fine
      sediments originating from the estuary, a local input from a long-sea sewage
      outfall and occasional high runoff episodes following torrential rain. The
      Sediment Quality Triad approach, combining environmental chemistry (namely
      organic contaminants), macrofaunal benthic communities and laboratory sediment
      toxicity assays, was performed on sediment samples from 20 sites. The samples
      were collected before the outfall commenced operation and four years after
      commissioning, in order to evaluate the relative magnitudes of the three
      potential sources of disturbance. The sediment contamination created by the
      estuary was identified as the most important cause of reduced sediment quality,
      as disturbance in all three components of the Sediment Quality Triad were only
      found in a site located near the estuary.

PMID- 15245981
TI  - Chemical characterization of porewaters in an intertidal mudflat of the Seine
      estuary: relationship to erosion-deposition cycles.
AB  - A seasonal field study was carried out in the Seine estuary to determine the
      chemistry of sediment porewaters using the 'peeper' technique and changes in the
      elevation of the mudflats using the 'Altus' technique. This approach allowed us
      to evaluate the release of nutrients and to link these releases to the sediment
      hydrodynamics. Our results show that nutrient and organic matter cycling in a
      Seine estuary mudflat exhibits a seasonal behaviour, which is mainly influenced
      by variations in hydrodynamics. Sediments, rich organic matter, were input during
      floods and they were mineralized during summer and autumn, releasing nutrients
      and dissolved organic carbon into the sediment porewaters. The nutrient release,
      including ammonium, is mainly linked to the mineralization of organic matter,
      while the release of phosphate is delayed. The delay could be the result of
      phosphate association with organic matter and/or its co-precipitation with
      calcium and iron.

PMID- 15245982
TI  - Evaluation of metal contamination in coastal sediments of the Bay of Bengal,
      India: geochemical and statistical approaches.
AB  - Surface sediment samples collected from the inner shelf region of the Bay of
      Bengal, were analysed for the major elements and total and acetic acid available
      trace elements (Al, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, Si, Zn) to
      evaluate geochemical processes influencing their distribution. Major elemental
      analysis showed that the sediments had high concentrations of Si and relatively
      low concentrations of Al and Fe. Both major elemental and trace metal
      concentrations indicated that the sediments represent weathered products of
      granite and charnockite. Normalization of metals to Al indicated relatively high
      enrichment factors for Pb, Cd, Zn and Cr. The higher proportions of nondetrital
      Pb (66%), Cd (41%) and Co (28%) reveal metal contamination due to anthropogenic
      inputs. Factor analysis (FA) identified six possible types of sedimentological
      and geochemical associations. The dominant factor accounting for 26.9% of the
      total variance identifies an anthropogenic input and accumulation of nondetrital
      Cd, Co, Cr, Ni and Pb. Association of these metals with CaCO3 reveals that shell
      fragments in the surface sediments are likely act as a carrier phase for
      nondetrital metals. The results are discussed in the context of the sources and
      pathways of elements in the Bay of Bengal.

PMID- 15245983
TI  - Eutrophication in the Polish coastal zone: the past, present status and future
      scenarios.
AB  - In the Baltic Sea eutrophication processes have accelerated in the past 50 years
      of the 20th century and presently there exists a major ecological problem for
      this sea. The Polish coastal zone of the southern Baltic Sea is the recipient of
      riverine inputs from two major sources, namely the Odra and Vistula, as well as a
      number of smaller rivers along the central coast. Hence, the entire coastal zone
      remains under severe anthropogenic pressure. The variability of nutrient
      concentrations, especially the winter nutrient pool in the euphotic zone, summer
      level of total nitrogen and total phosphorus, together with such eutrophication
      indicators as water oversaturation with oxygen and the summer oxygen minimum,
      were analysed in the data time series 1959-2001. The temporal trends were
      investigated using linear regression and the non-parametric Whirsch test. The
      future characteristics of the Baltic Sea are discussed taking into account the
      development of driving forces.

PMID- 15245984
TI  - Dreissena polymorpha (Bivalvia: Dreissenidae) in the Neva Estuary (eastern Gulf
      of Finland, Baltic Sea): is it a biofilter or source for pollution?
AB  - The zebra mussel Dreissena polymorpha, a ponto-caspian byssate bivalve, forms
      permanent dense populations along the shoreline in the northern part of the inner
      Neva Estuary. Its total biomass along a 17 km transect reached 4980 tons (mean
      1060 g m(-2)) in 2000 and 6510 tons (mean 1385 g m(-2)) in 2001. Being persistent
      and abundant, the zebra mussel populations played an important role in benthic
      pelagic coupling in inner Neva River Estuary. The D. polymorpha population
      released up to 514 kg day(-1) of dissolved inorganic phosphorus and was,
      therefore, a major source of bioavailable nutrients in the area. Mussel beds were
      also efficient biofilters and precipitate 15,020 kg day(-1) of particulate
      organic matter during the warm season. About 50% of precipitated matter had a
      relatively long retention time, being utilized within zebra mussel populations,
      while the rest was deposited as faeces and pseudofaeces and served as a source
      for organic pollution to the eastern Gulf of Finland.

PMID- 15245985
TI  - Plankton of the Baltic estuarine ecosystems with emphasis on Neva Estuary: a
      review of present knowledge and research perspectives.
AB  - Different levels of eutrophication and pollution in the Baltic coastal waters in
      general, and in estuaries particularly define variations in the buffering
      capacity of ecosystems of these important filter zones between rivers and the
      adjacent Baltic Proper. Phyto- and zooplankton in the estuaries form important
      components of the pelagic food webs that participate in producing and structuring
      the matter, energy, and information fluxes in the ecosystems. Due to salinity
      gradients, estuaries provide a large variety of aquatic habitats for native
      populations of marine, brackish and fresh water plankton species. Non-indigenous
      planktonic species that expand their bio-geographical range and invade the Baltic
      coastal ecosystems also find favourable environments, establish permanent
      populations there, and impact aboriginal ecosystems. The dynamics of abundance,
      species diversity, population structure, productivity of planktonic communities,
      and peculiarities of trophic interactions in different Baltic estuaries are
      influenced by a number of common environmental factors. Being measured on the
      unified basis and monitored, changes (or stability) of structural and functional
      parameters of plankton communities can serve as indicators of alterations to the
      ecosystems. Comparative analyses and quantitative estimates of long-term changes
      in phyto- and zooplankton can contribute to evaluation of functional response of
      Baltic coastal ecosystems to anthropogenic stress. Both theoretical (modeling)
      and empirical studies of interactions within plankton communities aimed at the
      assessment of the role of planktonic organisms in water quality regulation, and
      applicability of these data for the evaluation of the status of ecosystems and
      their management can be considered as major goals for the future investigations
      in Baltic estuaries.

PMID- 15245986
TI  - Effects of pollution on zooplankton abundance and distribution in two estuaries
      of the Basque coast (Bay of Biscay).
AB  - The abundance and spatial distribution of mesozooplankton were compared in the
      euhaline region of the polluted Bilbao estuary and the unperturbed Urdaibai
      estuary. The environmental variables measured were salinity, temperature,
      dissolved oxygen saturation, chlorophyll a, particulate organic matter and Secchi
      disk depth. Differences in the environmental variables and zooplankton between
      the estuaries and within the estuaries were tested statistically. Differences in
      the patterns of mesozooplankton abundance with salinity in each estuary indicated
      that they were affected by pollution in the Bilbao. Total mesozooplankton, and
      several mesozooplankton categories were more abundant in the Bilbao at higher
      salinities but in the Urdaibai at lower salinities. Therefore, we deduced that,
      in the Bilbao, zooplankton abundance was enhanced by the moderate pollution at
      the outer euhaline zone and limited by the poorer conditions of the inner zone.
      The response of the various zooplankton categories to the pollution is discussed.

PMID- 15245987
TI  - Detection of PAHs in seawater using surface-enhanced Raman scattering (SERS).
AB  - The laboratory characterization of a field-operable surface-enhanced Raman
      scattering sensor (SERS optode) is presented for the detection of aromatic
      hydrocarbons in seawater. The sensor has been developed for deployment with a
      robust underwater spectrograph. To meet the demands of the harsh seawater
      application, sol-gel derived SERS substrates were used. The calibration curves of
      six PAHs were determined to be of Langmuir adsorption isotherm type with limits
      of detection ranging from the microg l(-1) to ng l(-1) level. The experimentally
      determined adsorption constants varied strongly with the molecular weight of the
      analytes and correlated with their solubility. A mixture of five PAHs dissolved
      in seawater was investigated to demonstrate the utility of this method for
      screening. Emphasis was put on the interference from suspended particulate matter
      (SPM). The Raman measurement with backscattering configuration was shown to be
      immune against turbidities up to 1000 NTU. The physico-chemical interference
      arising from adsorption by the sediment was measured on-line by adding sediment
      to a PAH-spiked solution. According to the calibration curve, the PAH
      concentration decrease corresponded to more than 98% of the analyte being
      scavenged by the sediment.

PMID- 15245988
TI  - Transient oceanic and tidal contributions to water exchange and residence times
      in a coastal upwelling system in the NE Atlantic: the Pontevedra Ria, Galicia.
AB  - An analysis of the intra-annual variability of hydrographic residence times, tau,
      is presented for the Pontevedra Ria--a large coastal system in NW Spain with a
      deep, unobstructed connection with the Atlantic Ocean. Ria-offshore water
      exchange and tau were quantified with an iterative approach to the fraction of
      freshwater method using 23 quasi-steady state water-salt budgets. Excluding
      prolonged flushing due to downwelling events at the end of the upwelling season,
      mean was 6 +/- 2 day in the central ria and 2 +/- 1 day in the internal ria. The
      tidal contribution, equal to 10-25% of total water renewal, was quantified for
      the first time for a Galician ria with the hydrodynamic model estuarine
      contaminant simulator (ECoS). The relationship between tau and residual
      freshwater input, Qz, was atypical, since Qz played a minor role in water
      exchange in comparison to periodic upwelling of East North Atlantic Central Water
      (ENACW) from the continental shelf mainly during spring and summer. During
      positive upwelling stress, the intrusion of ENACW into the ria produced enhanced
      flushing and tau < 4 day in the central ria and < 2 days in the internal ria.
      Under downwelling favourable conditions, water was retained and tau prolonged to
      >8 and >5 days, respectively. A quantitative parameterisation of tau with
      upwelling and Qz was weakly significant, due to the short-term variability in ria
      salinity. This paper elucidates problems associated with the use of water budgets
      to transient coastal systems such as the Pontevedra Ria.

PMID- 15245989
TI  - Dynamics of particulate major and trace elements in the lower reaches of the
      Daugava River and adjacent area of the Gulf of Riga (Baltic Sea).
AB  - Suspended particulate matter (SPM) was collected in the freshwater-seawater
      mixing zone in the lower reaches of the Daugava River (Latvia) and adjacent
      marine area, during five cruises in 1998-2001. The study focused on
      biogeochemical phase exchange processes. SPM in the freshwater was found to be
      mainly allochthonous with a high content of organic matter, Mn and sorbed
      phosphate. Property-salinity plots suggested flocculation of humic-Fe complexes
      across the salinity gradient. The variability of sorbed phosphate was related to
      particulate Fe, although no dependence on pH and ionic strength was observed. The
      Mn contents of SPM mainly follow conservative mixing, but there are also
      indications of interface exchange of Mn in the mixing zone. The geochemical
      behaviour of particulate Al appears to differ from that of Fe. In early spring,
      trace element contents in SPM (Cr, Ni, Cu, Zn, Cd, Pb) correlate tightly with
      particulate organic matter, whose distribution is linked to phytoplankton
      distributions.

PMID- 15245990
TI  - Monitoring of organic pollutants in coastal waters of the Gulf of Gdansk,
      Southern Baltic.
AB  - This paper presents an overview of changes in organic pollution of coastal waters
      of the Gulf of Gdansk (Baltic Sea). Toxic pollutants including volatile organic
      compounds (VOC), volatile organohalogen compounds (VOX), chlorophenols,
      phenoxyacids, polychlorinated biphenyls (PCBs) and polycyclic aromatic
      hydrocarbons (PAHs) were determined in seawater from the Gulf of Gdansk coastal
      waters in the period 1996-2001. In the case of the Gulf of Gdansk, non
      conservative behaviour of VOC was observed due to random temporal and spatial of
      inputs along the Vistula estuary and to the dilution of VOC-enriched river water
      with seawater. The concentrations of VOX in seawater decreased throughout the
      period and the concentrations of VOX were in the range of few ng dm(-3) up to 250
      ng dm(-3), similar to estuaries elsewhere. The average concentrations of
      chlorophenols and phenoxyacids were between 0.1 and 6.0 and 0.05 and 2.2 microg
      dm(-3), respectively. However, remarkably high concentrations of 2,4
      dichlorophenol (6 microg dm(-3)) were obtained in samples collected from the
      Vistula River. Generally concentrations of PCBs did not exceed few ng dm(-3) with
      the exception of 1999, when all samples exhibited elevated concentrations of
      PCBs. In addition, higher concentrations of PCBs in the open sea compared to
      river waters suggested localised inputs. Due to the ability of most organic
      pollutants to bioaccumulate and biomagnify, especially the persistent organic
      pollutants, continued monitoring is of crucial importance for the health of
      marine life in the Gulf of Gdansk.

PMID- 15245991
TI  - Methods for the study of lipid metabolism in neurons.

PMID- 15245992
TI  - Purification of caveolae by affinity two-phase partitioning using biotinylated
      antibodies and NeutrAvidin-dextran.
AB  - A new concept for affinity two-phase partitioning was tested. The partitioning
      was based on the interaction of target membranes with a primary antibody which,
      in turn, interacted with a biotinylated secondary antibody and NeutrAvidin
      dextran in a poly(ethylene glycol)/dextran two-phase system. Caveolae selectively
      redistributed from the top phase to the NeutrAvidin-dextran-containing bottom
      phase by employing anti-caveolin as the primary antibody. This immunoaffinity
      approach was more selective than the established sucrose gradient centrifugation
      method and resulted in highly purified caveolae from Triton X-100-treated liver
      and lung plasma membranes. The same approach, employing other selective primary
      antibodies, should facilitate the purification also of other membrane fractions.

PMID- 15245993
TI  - Mapping spatial proximities of sulfhydryl groups in proteins using a fluorogenic
      cross-linker and mass spectrometry.
AB  - Chemical cross-linking of proteins in combination with mass spectrometric
      analysis of the reaction products has gained renewed interest as a method of
      obtaining distance constraints within a protein and determining a low-resolution
      three-dimensional structure. We present a method for identifying spatially close
      sulfhydryl groups in proteins employing chemical cross-linking with the
      fluorogenic, homobifunctional cross-linker dibromobimane, which cross-links thiol
      pairs within approximately 3-6A. The applicability of our strategy was
      demonstrated by cross-linking the sulfhydryl groups of Cys-18 and Cys-78 in gamma
      crystallin F, which are within a distance of 3.57A according to the X-ray
      structure. Intramolecularly cross-linked gamma-crystallin was first separated
      from reaction side products by reversed-phase chromatography on a C-4 column.
      Subsequently, the fraction containing the reacted protein was enzymatically
      digested with trypsin, and the resulting peptide mixture was separated by a
      second reversed-phase chromatographic step on a C-18 column, in which the cross
      linked peptides were tracked by their fluorescence. The cross-linking product
      between Cys-18 and Cys-78 in gamma-crystallin F was identified by matrix-assisted
      laser desorption/ionization-time of flight mass spectrometry. This strategy
      presents a rapid method for mapping sulfhydryl groups separated by a distance of
      approximately 3-6A within a protein.

PMID- 15245994
TI  - Effects of detergent alkyl chain length and chemical structure on the properties
      of a micelle-bound bacterial membrane targeting peptide.
AB  - The effects of phospholipid or detergent chain length on the structure and
      translational diffusion coefficient of the membrane-targeting peptide
      corresponding to the N-terminal amphipathic sequence of Escherichia coli enzyme
      IIA(Glc) were investigated by nuclear magnetic resonance (NMR) spectroscopy.
      Three anionic phospholipids (dihexanoyl phosphatidylglycerol, dioctanoyl
      phosphatidylglycerol, and didecanoyl phosphatidylglycerol) and four lipid
      mimicking anionic detergents (sodium hexanesulfonate, 2,2-dimethyl-silapentane-5
      sulfonate, sodium nonanesulfonate, and sodium dodecylsulfate) were evaluated. In
      all cases, the cationic peptide adopts an amphipathic helical structure. While
      the chain length of the two-chain phospholipids has a negligible effect on the
      peptide conformation, the effect of chain length of those single-chain detergents
      on the helix length is more pronounced. The diffusion coefficients of the
      peptide/micelle complexes were found to correlate with the chain lengths of both
      the lipid and the detergent groups. Taken together, short-chain anionic
      phospholipids are proposed to be useful membrane-mimetic models for the
      structural elucidation of membrane-binding peptides such as cationic
      antimicrobial peptides. DSS does not form micelles by itself according to the
      diffusion coefficient data, but it does associate with this cationic peptide.
      Consequently, both DSS and its analog may be chosen as NMR chemical shift
      reference compounds depending on the nature of the biomolecules under
      investigation.

PMID- 15245995
TI  - A method for selective conjugation of an analyte to enzymes without unwanted
      enzyme-enzyme cross-linking.
AB  - The conjugation of a ligand to an enzyme is often a necessary step in the
      development of enzyme-linked immunoassays. Such conjugation is typically
      accomplished by reacting an amine with a carboxyl functional group in the
      presence of an activator such as a carbodiimide. However, one enzyme's free
      carboxyl groups often react with another's free amino groups and a large amount
      of cross-linking between enzyme molecules occurs; few discrete enzyme molecules
      conjugated only to the ligand of interest are produced. Hence, it is necessary to
      carry out laborious chromatographic purification steps or to make an activated
      ligand such as an N-hydroxysuccinimide ester. This too can be a difficult task
      because N-hydroxysuccinimide esters are not stable in protic solvents and many
      biological ligands that would be of interest are poorly soluble in organic
      solvents. This difficulty may limit the quantity and yield of product. We
      describe a method that eliminates enzyme-enzyme cross-linking by blocking the
      solvent-accessible carboxyl groups of horseradish peroxidase and alkaline
      phosphatase, with dialysis being the only purification step necessary. We are
      consequently able to produce enzyme-ligand conjugates in high purity and in large
      quantity with little effort and in a relatively short period of time.

PMID- 15245996
TI  - Reporter substrates for assessing the activity of the hepatitis C virus NS3-4A
      serine protease in living cells.
AB  - We describe a versatile system for monitoring the activity of the NS3-4A serine
      protease of the hepatitis C virus (HCV) in mammalian cells. The system relies on
      coexpression of the protease and of an artificial substrate containing a reporter
      domain and an intracellular targeting sequence separated by a NS3-4A-specific
      cleavage site. We constructed two different substrates suitable for different
      applications. The first substrate secretory alkaline phosphatase-1 (SEAP-1)
      harbors the NS3-4A cleavage site inserted between the SEAP and a membrane anchor
      featuring an endoplasmic reticulum retention sequence. The arrangement of this
      substrate is such that SEAP is secreted in the extracellular medium depending on
      the NS3 protease activity. We show that SEAP-1 can be used to evaluate the
      activity of NS3-4A inhibitors in living cells. In the second substrate (CD8-1),
      SEAP is replaced by the extracellular domain of the lymphocyte surface antigen
      CD8 alpha. The arrangement of this substrate is such that the CD8 alpha domain is
      transported to the cell surface upon NS3-4Ap cleavage and remains associated with
      the plasma membrane as an integral membrane protein. We show that CD8-1 can be
      used for selecting cells capable of supporting HCV replication.

PMID- 15245997
TI  - High-throughput fluorescence spectroscopic analysis of affinity of peptides
      displayed on bacteriophage.
AB  - Fluorescence spectroscopy titrations, although widely used to analyze binding
      affinity, are not an efficient screening method for detecting high-affinity
      binding among a large number of available ligands, such as during bacteriophage
      display selections. We hypothesize that a miniaturized, high-throughput
      fluorescence spectroscopy assay can be used to efficiently analyze selection
      results by applying the Langmuir equation to the binding data to estimate
      affinity constants for a large number of ligands, either as synthesized molecules
      or as displayed on bacteriophage. Here, bacteriophage-display-derived peptides
      specific for the Thomsen-Friedenreich disaccharide are used to develop a high
      throughput fluorescence spectroscopy screening method, which uses one binding
      partner labeled with a fluorescent dye and different concentrations of a second
      partner to analyze binding affinity in bacteriophage display selections. The
      affinity constants derived from binding isotherms prepared using the new system
      accurately replicate those derived from standard spectroscopy titrations.
      Furthermore, the technique correctly defined the affinity constant describing
      binding of a cognate epitope peptide by a monoclonal antibody. Finally, we have
      applied the technique to analysis of binding affinity by ligands displayed on
      bacteriophage, which suggests that this technique could be used to monitor
      bacteriophage enrichment during selections.

PMID- 15245998
TI  - A combination of labeled and unlabeled antibody enables self-calibration and
      reduction of sample matrix effects in immunoassay.
AB  - Sample matrices interfering with analyte determinations, termed matrix effects,
      are one of the factors limiting the more widespread use of environmental
      immunoassays. Previous attempts to reduce matrix effects have focused on
      particular assays in specific matrices rather than on general methods. Here we
      describe a novel method to eliminate one class of matrix effects in immunoassay,
      independent of the particular matrix or analyte. The method is demonstrated with
      a model system detecting estradiol in either a 10% methanol or a 5% dimethyl
      sulfoxide matrix. Fluorescently labeled antiestradiol antibody is introduced as
      the detecting antibody and excess unlabeled antiestradiol antibody is included as
      a reference antibody. The binding of the excess reference antibody to the sample
      analyte artificially creates a sample containing no free analyte to bind to the
      detecting antibody. This allows estimation of the fluorescent signal for "zero"
      analyte in the actual sample matrix. The solvents employed as model systems
      reduce the affinity of the detecting antibody and cause false positive results at
      low estradiol concentrations and false negative results at high concentrations.
      The proposed reference method, including addition of the reference antibody,
      resulted in a self-calibrating assay in which the matrix effects, both positive
      and negative, were completely eliminated.

PMID- 15245999
TI  - The development of a continuous isothermal titration calorimetric method for
      equilibrium studies.
AB  - A continuous isothermal titration calorimetry (cITC) method for microcalorimeters
      has been developed. The method is based on continuous slow injection of a titrant
      into the calorimetric vessel. The experimental time for a cITC binding experiment
      is 12-20 min and the number of data points obtained is on the order of 1000. This
      gives an advantage over classical isothermal titration calorimetry (ITC) binding
      experiments that need 60-180 min to generate 20-30 data points. The method was
      validated using two types of calorimeters, which differ in calorimetric
      principle, geometry, stirring, and way of delivering the titrant into the
      calorimetric vessel. Two different experimental systems were used to validate the
      method: the binding of Ba(2+) to 18-crown-6 and the binding of cytidine 2'
      monophosphate to RNAse A. Both systems are used as standard test systems for
      titration calorimetry. Computer simulations show that the dynamic range for
      determination of equilibrium constants can be increased by three orders of
      magnitude compared to that of classical ITC, making it possible to determine high
      affinities. Simulations also show an improved possibility to elucidate the actual
      binding model from cITC data. The simulated data demonstrate that cITC makes it
      easier to discriminate between different thermodynamic binding models due to the
      higher density of data points obtained from one experiment.

PMID- 15246000
TI  - Amperometric glucose biosensor based on adsorption of glucose oxidase at platinum
      nanoparticle-modified carbon nanotube electrode.
AB  - A new amperometric biosensor, based on adsorption of glucose oxidase (GOD) at the
      platinum nanoparticle-modified carbon nanotube (CNT) electrode, is presented in
      this article. CNTs were grown directly on the graphite substrate. The resulting
      GOD/Pt/CNT electrode was covered by a thin layer of Nafion to avoid the loss of
      GOD in determination and to improve the anti-interferent ability. The
      morphologies and electrochemical performance of the CNT, Pt/CNT, and
      Nafion/GOD/Pt/CNT electrodes have been investigated by scanning electron
      microscopy, cyclic voltammetry, and amperometric methods. The excellent
      electrocatalytic activity and special three-dimensional structure of the enzyme
      electrode result in good characteristics such as a large determination range (0.1
      13.5mM), a short response time (within 5s), a large current density (1.176 mA cm(
      2)), and high sensitivity (91mA M(-1)cm(-2)) and stability (73.5% remains after
      22 days). In addition, effects of pH value, applied potential, electrode
      construction, and electroactive interferents on the amperometric response of the
      sensor were investigated and discussed. The reproducibility and applicability to
      whole blood analysis of the enzyme electrode were also evaluated.

PMID- 15246001
TI  - A disposable amperometric immunosensor for alpha-1-fetoprotein based on enzyme
      labeled antibody/chitosan-membrane-modified screen-printed carbon electrode.
AB  - A screen-printed three-electrode system is fabricated to prepare a novel
      disposable screen-printed immunosensor for rapid determination of alpha-1
      fetoprotein (AFP) in human serum. The immunosensor is prepared by entrapping
      horseradish peroxidase (HRP)-labeled AFP antibody in chitosan membrane to modify
      the screen-printed carbon electrode. The membrane is characterized with scanning
      electron microscope and electrochemical methods. After the immunosensor is
      incubated with AFP at 30 degrees C for 35 min, the access of the active center of
      HRP catalyzing the oxidation reaction of thionine by H(2)O(2) is partly
      inhibited. In presence of 1.2 mM thionine and 6 mM H(2)O(2), the electrocatalytic
      current decreases linearly in two concentration ranges of AFP from 0 to 20 and
      from 20 to 150 ng/mL with a detection limit of 0.74 ng/mL. The immunosensor shows
      an acceptable accuracy compared with those obtained from immunoradiometric
      assays. The interassay coefficients of variation are 6.6 and 4.2% at 10 and 100
      ng/mL, respectively. The storage stability is acceptable in pH 7.0 phosphate
      buffer solution at 4 degrees C for more than 10 days. The proposed method can
      detect the AFP through one-step immunoassay and would be valuable for clinical
      immunoassay.

PMID- 15246002
TI  - Identification of biogenic organotellurides in Escherichia coli K-12 headspace
      gases using solid-phase microextraction and gas chromatography.
AB  - Escherichia coli JM109 cells, expressing the genes encoded in a 3.8-kb
      chromosomal DNA fragment from Geobacillus stearothermophilus V, produced volatile
      organotellurium compounds which were released into the headspace gas above liquid
      cultures when amended with tellurite anions in micromolar amounts. Headspace
      sampling was achieved using gas-syringe extraction or solid-phase microextraction
      using carboxen-polydimethysiloxane fibers. In addition to dimethyl telluride and
      dimethyl ditelluride, two new organometalloidal compounds were detected using gas
      chromatograph with mass spectrometric or fluorine-induced chemiluminescence
      detection. These compounds are methanetellurol and dimethyl tellurenyl sulfide.
      The significance of these findings with regard to the current knowledge about
      bacterial tellurite resistance is discussed.

PMID- 15246003
TI  - The use of Fourier transform infrared spectroscopy to assay for urease from
      Pseudomonas aeruginosa and Canavalia ensiformis.
AB  - A novel assay method was investigated for urease (EC 3.5.1.5) from Pseudomonas
      aeruginosa and Canavalia ensiformis by Fourier transform infrared spectroscopy.
      This enzyme catalyzed the hydrolysis of urea in phosphate buffer in deuterium
      oxide ((2)H(2)O). The intensities of the bicarbonate bands maxima at 1625 and
      1365 cm(-1) and of the amide I band at 1605 cm(-1) were measured as a function of
      time to study the kinetics of urea hydrolysis. The extinction coefficients
      epsilon of urea and bicarbonate were determined to be 0.72, 0.48, and 0.56 mM(
      1)cm(-1) at 1625, 1605, and 1365 cm(-1), respectively. The initial velocity is
      proportional to the enzyme concentration by using the ureases from both
      C.ensiformis and P. aeruginosa. The kinetic constants (V(max), K(m), and K(cat))
      determined by Lineweaver-Burk plot were 532.2 U mg(-1) protein, 6.4mM, and 806.36
      s(-1), respectively. These data are in agreement with the results obtained by a
      spectrophotometric method using a linked assay based on glutamate dehydrogenase
      in aqueous media. Therefore, this spectroscopic method is highly suited to assay
      for urease activity and its kinetic parameters by using either cell-free extracts
      or purified enzyme preparations with an additional advantage of performing a real
      time measurement of urease activity.

PMID- 15246004
TI  - An assay for sphingosine kinase activity using biotinylated sphingosine and
      streptavidin-coated membranes.
AB  - Sphingosine kinase catalyses the phosphorylation of sphingosine to generate
      sphingosine 1-phosphate, a lipid signaling molecule implicated in roles in a
      diverse range of mammalian cell processes through its action as both a ligand for
      G-protein-coupled cell-surface receptors and an apparent intracellular second
      messenger. This paper describes a rapid, sensitive, and reproducible assay for
      sphingosine kinase activity using biotinylated sphingosine (biotinyl-Sph) as a
      substrate and capturing the phosphorylated product with streptavidin-coated
      membranes. We have shown that both human sphingosine kinase 1 and 2 (hSK1 and
      hSK2) can efficiently phosphorylate biotinyl-Sph, with K(m) values similar to
      those of sphingosine. The assay utilizing this substrate has high sensitivity for
      hSK1 and hSK2, with detection limits in the low-femtomole range for both purified
      recombinant enzymes. Importantly, we have also demonstrated the capacity of this
      assay to measure endogenous sphingosine kinase activity in crude cell extracts
      and to follow changes in this activity following sphingosine kinase activation.
      Together, these results demonstrate the potential utility of this assay in both
      cell-based analysis of sphingosine kinase signaling pathways and high-throughput
      screens for agents affecting sphingosine kinase activity in vitro.

PMID- 15246005
TI  - Integration of hydrogen/deuterium exchange and cyanylation-based methodology for
      conformational studies of cystinyl proteins.
AB  - This report documents the feasibility and advantages of integrating
      hydrogen/deuterium exchange (HDX) methodology with cyanylation (CN)-based
      methodology to determine the conformation of cystinyl proteins and intermediates
      during refolding. The CN-based methodology can be used to trap, identify, and
      preserve the disulfide structure of a given cystinyl protein folding
      intermediate, while the HDX methodology can be used to assess other
      conformational features of the intermediate. Specifically, in this study, CN
      based methodology was used to trap a 1-disulfide bond and a 2-disulfide
      intermediate of long Arg(3) insulin-like growth factor-I (LR(3)IGF-I), which was
      then exposed to HDX using D(2)O at pD 6.8 and subsequently digested with pepsin
      before analysis by matrix-assisted laser desorption/ionization mass spectrometry.
      The HDX results show an increasing degree of secondary and tertiary structure as
      a function of disulfide bond formation. In addition, the HDX results for two
      overlapping peptic fragments suggest that a segment of the polypeptide exists in
      two conformations, which can be distinguished by HDX and pepsin. These results
      from HDX mass spectrometry are in reasonably good agreement with those from
      nuclear magnetic resonance studies of native LR(3)IGF-I and IGF-I, in which
      approximately 5000 times more material was used than in our study. Indications
      are that the integrated use of HDX and CN-based methodologies will be effective
      in studying the refolding of cystinyl proteins at the subnanomole level.

PMID- 15246006
TI  - Fluorescence polarization assay and inhibitor design for MDM2/p53 interaction.
AB  - MDM2 is an important negative regulator of the tumor suppressor protein p53 which
      regulates the expression of many genes including MDM2. The delicate balance of
      this autoregulatory loop is crucial for the maintenance of the genome and control
      of the cell cycle and apoptosis. MDM2 hyperactivity, due to
      amplification/overexpression or mutational inactivation of the ARF locus,
      inhibits the function of wild-type p53 and can lead to the development of a wide
      variety of cancers. Thus, the development of anti-MDM2 therapies may restore
      normal p53 function in tumor cells and induce growth suppression and apoptosis.
      We report here a novel high-throughput fluorescence polarization binding assay
      and its application in rank ordering small-molecule inhibitors that block the
      binding of MDM2 to a p53-derived fluorescent peptide.

PMID- 15246007
TI  - Ultrafiltration-based assay for heparanase activity.
AB  - Heparanase, a mammalian endoglycosidase that specifically cleaves heparan sulfate
      (HS), has been found in many tissues. Platelet, liver, and placenta have been
      abundant sources for the study of the enzyme. Notably, certain malignant cells
      also have been found to produce large amounts of the enzyme, the levels of which
      often correlate with their invasive and metastatic properties. To study roles of
      heparanase in various biological situations, a reliable method measuring the
      enzyme activity is indispensable. In the past, measurement of heparanase enzyme
      activity was done either by the detection of the degradation of fluorescent or
      radiolabeled HS chains by gel filtration procedures or by the use of radiolabeled
      substrate conjugated to solid matrices for the easy separation of degraded HS
      chains. A newly developed procedure, presented in this article, measures
      degradation of radiolabeled HS chains in the aqueous buffer by detecting their
      degradation products using an ultrafiltration device, the Centricon 30. This
      procedure has several advantages over previous assay procedures that involved
      tedious processing such as gel filtration chromatography of each sample or the
      preparation of substrate HS proteoglycans conjugated to a solid matrix. The
      simplicity of the new procedure allows a short setup time and a rapid processing
      of a large number of samples. Furthermore, the enzymatic reaction during the
      aqueous phase allows kinetic analyses in standard conditions.

PMID- 15246008
TI  - A one-step approach to obtain cell clones expressing tetracycline-responsive
      transactivators.
AB  - Despite the wide application of the tetracycline-regulated gene expression
      system, several drawbacks in establishing the system in in vitro-cultured cells
      have been described. Most of the problems are related to obtaining a reliable
      tetracycline-regulated cell clone, which often results in arduous labor. We
      describe here a new approach to facilitate the screening and selection of such
      cell clones. We have constructed a tetracycline-responsive plasmid that harbors
      an antibiotic resistance gene fused to the enhanced green fluorescent protein
      (EGFP) gene and the luciferase gene, both under the control of a bidirectional
      promoter. We demonstrate that the selection of tetracycline-regulated clones is
      highly simplified by using this plasmid. Only clones expressing the system in a
      functional manner are able to survive under antibiotic selection. In addition, a
      quick characterization of the responsiveness of the clones is possible by
      monitoring GFP expression in vivo.

PMID- 15246009
TI  - Automated affinity chromatography measurements of compound mixtures using a lab
      on-valve apparatus coupled to electrospray ionization mass spectrometry.
AB  - We report a fully automated affinity chromatography system using a lab-on-valve
      (LOV) apparatus coupled to an electrospray ionization ion-trap mass spectrometer
      (ESI-MS). The system allows simultaneous measurements of multiple ligand
      affinities to proteins immobilized on beads. Bead regeneration, column repacking,
      and repetitive measurements are achieved on the time scale of several minutes. In
      this study, the system was used to screen the binding of a peptide mixture to
      human and Trypanosoma brucei (T. brucei) truncated Pex5 (tPex5) proteins.
      Equilibrium dissociation constants (K(d)) were measured for T. brucei tPex5 and
      compared to the values obtained by a fluorescence-based competition assay. The
      three peptides that showed affinity toward tPex5 had K(d) values that were
      comparable in magnitude (within a factor of 5) and showed the same ranking order
      as those from manual fluorescence measurements. With 12 min of sample infusion,
      the entire sample-to-sample cycle takes about 15 min and can be repeated without
      any preparation between runs. For T. brucei tPex5 affinity measurements, 1 mg of
      protein was sufficient for 35 repetitive analyses in the automated LOV-ESI-MS
      apparatus. The system allows rapid determination of K(d) in the range of 10(-5)
      10(-7) M for sample mixtures and is suitable for screening a large number of
      compounds against multiple proteins.

PMID- 15246010
TI  - Determination of choline and ethanolamine plasmalogens in human plasma by HPLC
      using radioactive triiodide (1-) ion (125I3-).
AB  - For the purpose of developing highly sensitive and convenient determination of
      plasmalogens, the high-performance liquid chromatography (HPLC) method using
      radioactive iodine ((125)I) was investigated. Radioactive triiodide (1-) ion
      ((125)I(3)(-)), which is an actual iodine form capable of reacting with vinyl
      ether bond ([bond]CH(2)[bond]O[bond]CH[double bond]CH[bond]) of plasmalogens,
      could be safely and efficiently produced by oxidizing a commercial radioactive
      sodium iodine (Na(125)I) with hydrogen peroxide (H(2)O(2)) under acid condition
      (pH 5.5-6.0), which is called iodine-125 reagent. I(3)(-) specifically reacted
      with plasmalogens at the molar ratio of 1:1 in methanol, and 1 or 2 mol of
      plasmalogens was involved in the binding with iodine per iodine atom, resulting
      in the formation of stable iodine-binding phospholipids. The HPLC system with
      Diol column and acetonitrile/water as a mobile phase was available for separating
      iodine-binding phospholipids from nonbinding free iodine and for separately
      eluting iodine-binding phospholipids derived from choline and ethanolamine
      plasmalogens. Using iodine-125 reagent (1.85 MBq/ml), plasmalogens were
      detectable at high sensitivity of 10,000-15,000 cpm/nmol, which is more than 1000
      fold higher sensitivity than the classical determination with nonradioactive
      iodine. Plasmalogen concentrations in human plasma were measured with the HPLC
      system and determined as, on average, 129.1+/-31.3 microM (n=8) in a 1.2 content
      ratio of choline to ethanolamine plasmalogens, a concentration that nearly agrees
      with the value reported previously.

PMID- 15246011
TI  - Analysis of beta-carotene absorbance for studying structural properties of human
      plasma low-density lipoproteins.
AB  - A novel spectrophotometric assay for monitoring structural rearrangements of
      native low-density lipoproteins (LDL) is proposed. The approach is based on the
      analysis of the visible light absorbance maximum of lipoproteins at approximately
      461 nm assigned to beta-carotene situated in the hydrophobic parts of LDL. It
      offers a direct method to study the surface-interior coupling of the lipoprotein
      particle under physiological conditions. The detected signal is intrinsic to LDL
      and responsible for the most of the beta-carotene signal from the whole plasma.
      The negligible interference of beta-carotene absorbance due to the high-density
      lipoproteins is experimentally verified. Since beta-carotene absorbance belongs
      to the visible spectral region, no spectral overlapping/artifacts in plasma are
      expected. The signal sensitivity has been studied through conformational changes
      of LDL induced by ionic strength, by temperature, and by ligand binding. The
      results of caffeine binding to LDL indicate that there could be only one dominant
      type of binding site for caffeine on LDL particles. It can be concluded that
      visible spectrum characteristics of beta-carotene molecules offer advantages in
      LDL ligand binding studies which can possibly be extended to monitor the
      interactions of LDL directly in plasma.

PMID- 15246012
TI  - Quantitative analysis of sinistrin in serum with high-performance liquid
      chromatography for renal function testing.
AB  - Sinistrin, as inulin, is widely used as a marker for renal function testing. A
      reliable and accurate method with a simple sample preparation for the
      quantitative determination of sinistrin would be of advantage. We developed a
      high-performance liquid chromatography (HPLC)-based method with electrochemical
      detection for the quantitative measurement of sinistrin in serum and plasma.
      Sample preparation is easy and includes enzymatic removal of glucose,
      deproteinization, acid hydrolysis of sinistrin, and HPLC separation of fructose.
      The recovery of sinistrin from serum is the same as that from water and is near
      100%. The method presented has a linear range up to 500 mg/L. The results from
      our method are in agreement with a fully enzymatic quantification (regression
      coefficient 1.01, coefficient of variation 0.97). Sinistrin concentrations in
      aqueous solutions can be measured down to 2mg/L with a coefficient of variation
      of 5.7%. Quantification in serum is primarily limited by its physiological
      fructose content. The sensitivity of the described method is sufficient for its
      use in renal function testing. We describe a method for quantification of
      sinistrin which allows accurate measurements especially at low concentrations and
      low sample volumes. This laboratory method may be used for obtaining sinistrin
      pharmacokinetics in renal function testing.

PMID- 15246013
TI  - HPLC assay for guanidinoacetate methyltransferase.

PMID- 15246015
TI  - A high-throughput system to verify candidate interactors from yeast two-hybrid
      screening using rolling circle amplification.

PMID- 15246014
TI  - Determination of fraction unbound docetaxel using microequilibrium dialysis.

PMID- 15246016
TI  - Microplate screening assay to identify inhibitors of human catechol-O
      methyltransferase.

PMID- 15246017
TI  - An internal control for immunoblot analysis using the blotted membrane.

PMID- 15246018
TI  - Overproduction of eukaryotic SUMO-1- and SUMO-2-conjugated proteins in
      Escherichia coli.

PMID- 15246019
TI  - Adverse events of desirable gain in immunocompetence: the Immune Restoration
      Inflammatory Syndromes.
AB  - Augmentation of inflammation may occur during immune reconstitution in a
      immunocompromised host. This phenomenon is able to cause atypical inflammatory
      disorders, synonymously summarized as 'Immune Reconstitution Syndrome', 'Immune
      Restoration Disease' and 'Immune Restoration Inflammatory Syndrome' (IRIS).
      Immune reconstitution occurs, if temporarily use of immunosuppressive agents was
      terminated or if highly active antiretroviral therapy in human immunodeficiency
      virus positive individuals with secondary immunodeficiency was initiated.
      Unexpected deterioration of inflammatory disease and atypical clinical features,
      resembling symptoms of autoimmune disease may arise. They have to be
      distinguished from intercurrent infection and rheumatic disease, respectively.
      Treatment of IRIS would consist of both potential differential diagnoses: use of
      anti-inflammatory and immunosuppressive drugs like in autoimmune disorders as
      well as antimicrobial chemotherapy to decrease the burden of pathogen like in
      infectious disease. Therefore, awareness for IRIS is of increasing importance
      from a clinical point of view. However, diagnostic criteria and standards of
      treatment still have to be defined.

PMID- 15246020
TI  - Is damage in central nervous system due to inflammation?
AB  - The aim of this work was to review the inflammatory factors involved in central
      nervous system (CNS) inflammation and the damage associated to their
      participation in an inflammatory disease of CNS, multiple sclerosis in humans and
      experimental allergic encephalomyelitis in the murine model. Inflammation has an
      important repairing function, nevertheless frequently in the CNS inflammation is
      the cause of damage and it does not fulfill this repairing function as it happens
      in other compartments of the body. The inflammatory response in the CNS involves
      the participation of different cellular types of the immune system (macrophages,
      mast cells, T and B lymphocytes, dendritic cells) and resident cells of the CNS
      (microglia, astrocytes, neurons), adhesion molecules, cytokines and chemokines
      among other proteic components. During neuroinflammation chemotaxis is an
      important event in the recruitment of cells to the CNS. The lymphocyte
      recruitment implies the presence of chemokines and chemokine receptors, the
      expression of adhesion molecules, the interaction between lymphocytes and the
      bloodbrain barrier (BBB) endothelium, and finally their passage through the BBB
      to arrive at the site of inflammation. If this process is not controlled, is
      prolonged, inflammation loses its repairing function and can be the cause of
      damage. Usually neuroinflammation has the tendency to decline to damage, which
      would explain most of the CNS pathologies.

PMID- 15246021
TI  - Thrombogenicity of TNF alpha in rheumatoid arthritis defined through biological
      probes: TNF alpha blockers.
AB  - Rheumatoid arthritis is a disease at high cardiovascular risk. It has recently
      been shown that RA patients with more than 10 years disease duration present a
      risk of myocardial infarction more than three times higher than osteoarthritis
      controls. The major determinant is thought to be the chronic inflammatory
      process, driven by some key cytokines among which TNF alpha is thought to play
      the leading role in the majority of the patients. TNFalpha, therefore, once
      blocked by specific inhibitors like TNF alpha blockers (Infliximab, Etanercept)
      should profoundly decrease the cardiovascular risk. However, TNF blockers induce
      the appearance of autoimmunity though in a small minority of the patients. This
      autoimmunity is thought to be due to the poor clearance of apoptotic bodies once
      the systemic inflammation (CRP, SAP) is controlled by the specific blockers, and
      to the lack of control of some B cell populations producing autoantibodies to
      specific autoantigens. Among the autoantibodies arising during TNF blockade,
      anticardiolipin appear to be the most crucial with respect to the cardiovascular
      risk. The appearance of anticardiolipins at clinically significant levels appears
      to be driven by two possible mechanisms, one due to common infections of the
      urinary or upper airways tract during blockade of soluble TNF alpha, the other
      due to the escape of some autoreactive B cells during blockade of soluble and
      membranous TNF alpha. Since both autoantibodies related to infections as well as
      the high levels unrelated to infections, can be well controlled by appropriate
      therapies, clinicians should pay attention to the biological phenomenon before it
      becomes a clinical problem.

PMID- 15246022
TI  - T-cell vaccination in multiple sclerosis: update on clinical application and mode
      of action.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS). Autoreactive T cells specific for myelin antigens are considered to
      play a prominent role in the initiation of the local inflammatory response,
      ultimately leading to myelin damage. Several studies indicate that autoreactive T
      cells are not completely deleted in the thymus, but are part of the normal T cell
      repertoire. Accidentally activated autoreactive T cells, however, may not
      automatically lead to autoimmune disease. Several reports support the existence
      of peripheral regulatory networks that prevent the activation and expansion of
      pathogenic T cells. Anti-idiotypic and anti-ergotypic T cells are part of this
      regulatory network and are thought to control autoreactive T cells by recognition
      of certain clonotypic and ergotypic determinants. These clonotypic networks may
      not function properly in patients with MS. Immunization with attenuated
      autoreactive T cells, termed T cell vaccination (TCV), may enhance or restore the
      regulatory networks to specifically suppress the autoreactive T cells as shown in
      experimental autoimmune encephalomyelitis (EAE), a commonly used animal model for
      MS. In the past decade, TCV has been tested for MS in several clinical trails.
      This review summarizes these clinical trails and updates our current knowledge on
      the mode of action of T cell vaccination.

PMID- 15246023
TI  - New insights into the pathogenesis of dilated cardiomyopathy: possible underlying
      autoimmune mechanisms and therapy.
AB  - In the present study, autoimmune processes involved in the pathogenesis of
      dilated cardiomyopathy (DCM) are discussed. Genetic predisposition, persistent
      viral infection, and molecular mimicry have previously been described as the
      underlying mechanisms of the disease, and prevalence of autoantibodies (AABs)
      against several intra- and extracellular cardiotropic targets has been confirmed.
      These autoantibodies are able to disturb the normal physiological activity of the
      cardiomyocytes. They also could function as mediators in an activated immune
      system and direct a great deal of attention to injured tissue via (1) complement
      activation and (2) genesis of circulatory immunocomplexes (CICs) in association
      with self-antigens. The number as well as duration of accessible autoantigens or
      CICs seem to play an important role in activation of the antigen-presenting cells
      (APCs) and, consequently, promotion of autoimmunity. Since AABs play such a
      decisive role, their exclusion by immunoadsorption (IA) therapy has been
      discussed as a new approach in DCM treatment. Hitherto, all performed pilot
      studies using this approach have shown improvement in cardiac function and
      quality of life in the vast majority of treated DCM patients. The removal of
      circulating AABs may downregulate the autoimmune system, moderate the
      inflammatory signals, and hasten the recovery of the affected tissue.

PMID- 15246025
TI  - Sarcoidosis succumbs to antibiotics--implications for autoimmune disease.
AB  - From time to time there have been reports of autoimmune disease succumbing to
      tetracycline antibiotics, but many have assumed this was due to coincidence, or
      to some ill-defined 'anti-inflammatory property' of the tetracyclines. But now
      the inflammation of sarcoidosis has succumbed to antibiotics in two independent
      studies. This review examines the cell wall deficient (antibiotic resistant)
      bacteria which have been found in tissue from patients with sarcoidosis. It
      examines how such bacteria can infect the phagocytes of the immune system, and
      how they may therefore be responsible for not only sarcoid inflammation, but also
      for other autoimmune disease. Proof positive of a bacterial pathogenesis for
      Sarcoidosis includes not only the demonstrated ability of these studies to put
      the disease into remission, but also the severity of Jarisch-Herxheimer shock
      resulting from endotoxin release as the microbes are killed. Studies delineating
      the hormone responsible for phagocyte differentiation in the Th1 immune response,
      1,25-dihydroxyvitamin D, are discussed, and its utility as a marker of Th1 immune
      inflammation is reviewed. Finally, data showing that the behavior of this hormone
      is also aberrant in rheumatoid arthritis, systemic lupus erythematosus, and
      Parkinson's, raise the possibility that these diseases may also have a CWD
      bacterial pathogenesis.

PMID- 15246024
TI  - Transgenic analysis of scleroderma: understanding key pathogenic events in vivo.
AB  - Modern molecular genetic methods have allowed better understanding of established
      mouse models of scleroderma and also facilitated the development of new and
      better defined mouse strains for investigating the pathogenesis of the disease.
      The best characterized scleroderma animal model is the type 1 tight skin mouse
      (Tsk1). Backcrossing these animals with other mutant strains has been
      informative. These experiments implicate the IL-4 ligand-receptor axis in the
      development of skin fibrosis. Parallel expression analysis of genes using
      microarrays has provided insight into novel mediators of fibrosis including the C
      C chemokine MCP-3. Other experiments suggest that embryonically defined
      fibroblast-specific regulatory elements may be targets for activation in this
      model. The same lineage-specific elements have been used to selectively activate
      TGF beta signaling pathways in fibrosis to generate a novel model for scleroderma
      and also have been used to develop systems for ligand-dependent fibroblast
      specific genetic recombination that will allow further analysis key candidate
      genes implicated in scleroderma pathogenesis. Better mouse models will improve
      understanding of this intractable rheumatic disease and can be expected to
      ultimately lead to improved treatments and outcome.

PMID- 15246026
TI  - Endothelial dysfunction in rheumatoid arthritis: influence of HLA-DRB1 alleles.
AB  - Cardiovascular disease is the commonest cause of premature mortality in
      rheumatoid arthritis (RA) patients. Vascular endothelial injury is the primary
      event in atherosclerosis. It has been associated with endothelial dysfunction. We
      have recently observed that actively treated RA patients had endothelial
      dysfunction. HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, seem
      to be implicated in the development of endothelial dysfunction. These results
      underline the influence of genetic factors in the risk of atherosclerosis in RA
      patients.

PMID- 15246027
TI  - Is rheumatoid arthritis premature osteoarthritis with fetal-like healing?
AB  - Rheumatoid arthritis is now known to share many pathogenetic features with
      osteoarthritis including synovial activation with release of pro-inflammatory
      cytokines into the synovial fluid. As premature chondrocyte aging and
      dedifferentiation is increasingly accepted as integral to OA pathogenesis,
      premature aging of chondrocytes and perhaps subchondral bone may underlie RA.
      This hypothesis explains many otherwise enigmatic features of RA joint pathology
      such as the homing of pannus to cartilage. In addition, the surprising finding of
      mesenchymal precursor cells in RA joints has led to speculation that some aspect
      of RA pathogenesis involves an attempt to recapitulate the embryonic limb
      development program. In its totality, RA seems to consist of an attempt to
      regenerate damaged cartilage and subchondral bone in an adult organism. Since
      this is impossible, the best the pannus can do is to crawl through empty
      cartilage lacunae and replace the cartilage and subchondral bone with scar
      tissue. As opposed to fetal healing, inflammation is necessary to sustain and
      control the fibroproliferation. Two recently-discovered blood cell types seem to
      maintain and regulate fibroplastic states in humans: (1) CD34+ and/or monocytoid
      stem-cell precursors replace aging mesenchymal cells, and (2) regulatory-type
      adherent CD4+CD28-T cells control growth of those increasingly apoptosis
      resistant mesenchymal cells. Such cells occur at multiple sites in AID patients.

PMID- 15246028
TI  - Pulmonary hypertension in autoimmune rheumatic diseases.
AB  - Arterial pulmonary hypertension (PH) might be a complication of some autoimmune
      rheumatic diseases, specially systemic sclerosis. This form of arterial PH is
      indistinguishable from primary PH, characterised by the presence of plexiform
      lesions. Although for many years plexiform lesions have been considered end-stage
      scarring lesions, they are composed by actively proliferating endothelial cells
      that share many features with cancer cells. Endothelial cells within plexiform
      lesions in all forms of arterial PH show a decrease in the expression of
      vasodilator and anti-proliferative factors, and an increase in the expression of
      vasoconstrictor and angiogenic and mitogenic factors. These cells also show
      important alterations in growth and apoptosis key regulatory genes. Plexiform
      lesions are surrounded by inflammatory cell infiltrates, probably providing
      cytokines that may contribute to the endothelial cell proliferative process. All
      these data suggest that arterial PH might be seen as a proliferative endothelial
      cell process, which would open new therapeutic approaches for this devastating
      disease.

PMID- 15246029
TI  - What have we learned from a 10-year experience with the LUMINA (Lupus in
      Minorities; Nature vs. nurture) cohort? Where are we heading?
AB  - Recently, there has been an awareness of the variable phenotypic expression of
      numerous disorders between individuals from different ethnicities, systemic lupus
      erythematosus (SLE) one of them. These disparities probably arise from the
      interaction between genetic and non-genetic (environmental, socioeconomic
      demographic, cultural and behavioral) factors. To delineate the influence of
      these factors on SLE outcome, we established a multiethnic (Hispanic, African
      American and Caucasian) United States (US) early cohort (<5 years disease
      duration). Ten years later, interesting data have emerged from the LUMINA (Lupus
      in Minorities: Nature vs. nurture) cohort. For example, African Americans and
      Hispanics from Texas have a more severe disease than Caucasians and Hispanics
      from Puerto Rico. Lack of private insurance, acute SLE onset, expression of HLA
      DRB1*01 (DR1) and C4A*3 alleles were associated with higher disease activity,
      whereas age, the number of American College of Rheumatology criteria met, disease
      activity, corticosteroid use and abnormal illness behaviors were consistent
      predictors of damage. In turn, damage and poverty were found to predict
      mortality. We now plan to apply new approaches (genetic admixture) to deconfound
      the complex interaction between genetic and non-genetic factors influencing SLE
      outcome. These data may have impact on the development of policies aimed at
      eliminating health disparities in the US.

PMID- 15246030
TI  - Is primary biliary cirrhosis a model autoimmune disease?
AB  - Primary biliary cirrhosis (PBC) has been coined a model autoimmune disease. In
      fact, it does share many similarities with other autoimmune diseases, but there
      are striking differences that illustrate the uniqueness of the immunopathology.
      Firstly, similar to other autoimmune diseases, there is an intense humoral and
      cellular response to an intracytoplasmic antigen. There is also an overlap of the
      epitopes recognized by autoreactive CD4(+), CD8(+) T cells as well as B cells.
      Patients with PBC are also predominantly female, and there is a higher family
      history of other autoimmune diseases. In contrast, however, there are no specific
      HLA associations in PBC. Further, there are no spontaneous or induced animal
      models of PBC. In addition, early in the biliary lesions of PBC, there is an
      eosinophilic infiltration and, often, there are granulomas. Finally, unlike
      several other human autoimmune diseases, patients with PBC have recognition of
      but one major epitope, and there is no evidence for determinant spreading. Hence,
      although the immune response of PBC has been vigorously defined, there remain
      major gaps in understanding the most difficult issue of all, namely etiology.

PMID- 15246031
TI  - Heart, rheumatism and autoimmunity: Milan, Italy. February 5-7, 2004.

PMID- 15246032
TI  - Improving patient safety with technology.

PMID- 15246033
TI  - Patient safety. Remember who it's really for.
AB  - Patients appear in the patient safety agenda in three important places: first and
      foremost as the individual most likely to experience the positive benefits of
      good care or negative consequences of unsafe care; second, as surveyors of
      quality of care indicators; and finally, through their presence as patient
      representatives on institutional safety committees. However, patient safety
      programs largely address provider-interests, and many times overlook patient
      preferences and needs. Active engagement of the patient in all aspects of the
      patient safety agenda is necessary for its success. Patient safety, then,
      requires: a comprehensive agenda informed by patient preferences and experiences;
      an informed and motivated populace; mechanisms integrate safe practices and
      patient preferences, and investment in safety-enhancing devices and care
      strategies.

PMID- 15246034
TI  - Improving patient safety through informatics tools for shared decision making and
      risk communication.
AB  - This paper describes how informatics tools can support shared decision making and
      risk communication and thereby play an important role in enhancing patient
      safety. Using preference elicitation techniques and knowledge on risk
      communication, such tools can help patients understand their treatment options
      and associated short- and long-term benefits and risks, assist in the elicitation
      of patient preferences, and help patients and clinicians in making treatment
      choices with the highest likelihood of achieving desired patient outcomes.
      Important features of such tools are proposed, including: (1) Interactive
      tutorials to improve risk comprehension and prepare patients and clinicians for
      the decision making task; (2) choices between different presentation modes to
      meet patients' individual reading levels and presentation preferences; (3) risk
      calculations that account for individual risk profiles; (4) performance of
      necessary calculations to reach the actual decision; (5) automatic updates of
      evidence; and (6) the use of different preference-elicitation techniques.

PMID- 15246035
TI  - Managing the three 'P's to improve patient safety: nursing administration's role
      in managing information technology.
AB  - The Institute of Medicine's landmark report asserted that medical error is seldom
      the fault of individuals, but the result of faulty healthcare policy/procedure
      systems. Numerous studies have shown that information technology (IT) can shore
      up weak systems. For nursing, IT plays a key role in eliminating nursing
      mistakes. However, managing IT is a function of managing the people who use it.
      For nursing administrators, successful IT implementations depend on adroit
      management of the three 'P's: People, processes and (computer) programs. This
      paper examines critical issues for managing each entity. It discusses the
      importance of developing trusting organizations, the requirements of process
      change, how to implement technology in harmony with the organization and the
      significance of vision.

PMID- 15246036
TI  - Patient safety initiatives in Brazil: a nursing perspective.
AB  - The science development and technology application improvement in all areas of
      knowledge, including health care, represent an advance in patient care. The
      health care providers face challenges to accomplish complex procedures and
      treatments, which demand infrastructure, defined framework, constant process
      establishment and redesign of nursing care, based on a continuous outcomes
      evaluation. Therefore, this development requires nurses with advanced knowledge
      and skills. As the main health care provider in Brazilian hospitals, the nursing
      staff perform and control the majority of direct patient care procedures, and as
      such, nursing professionals can be responsible for triggering adverse events that
      can compromise patient safety. Research conducted in Brazil showed that the
      quality of health care delivery system and the results of care have significant
      variation nationwide. Health care professionals should be valued as the one who
      can promote patient safety, providing high quality care within cost-effective
      services. Technology is a key element to support and enhance the professional's
      performance. However, it is also important to promote and facilitate its
      implementation and development to retain a creative, engaged, skilled, satisfied,
      competent, and accountable professional capable of identifying and using
      technology resources in order to assure the quality of care for the population.

PMID- 15246037
TI  - Challenging the information gap--the patients transfer from hospital to home
      health care.
AB  - The purpose of this paper is to identify the information that nurses in hospitals
      exchange with nurses in home health care (HHC), and what nurses perceive to be
      the most significant information to exchange. METHOD: Nurses have an obligation
      to support and ensure continuity of patient care and to prevent an information
      gap when patients are transferred from one organizational of health care delivery
      to another organizational level, for example, from hospital to home health care.
      In an ongoing prospective study, nurses' pre-electronic nursing discharge note
      and their assessment of the information it was necessary to exchange at the same
      time was audited and analyzed. The results show variation in the completeness and
      content of the nursing discharge note. Nurses' understanding of the scope and
      content of information to be transmitted varies widely according to the context
      and the organizational health care level they work within. The implementation of
      an electronic nursing discharge note creates the opportunity to identify the
      accurate information elements that must be documented and exchanged between the
      nurses to ensure patient safety and inter-organizational continuity of care.

PMID- 15246038
TI  - Promoting patient safety through informatics-based nursing education.
AB  - The Institute of Medicine (IOM) Committee on Quality of Health Care in America
      identified the critical role of information technology in designing safe and
      effective health care. In addition to technical aspects such as regional or
      national health information infrastructures, to achieve this goal, healthcare
      professionals must receive the requisite training during basic and advanced
      educational programs. In this article, we describe a two-pronged strategy to
      promote patient safety through an informatics-based approach to nursing education
      at the Columbia University School of Nursing: (1) use of a personal digital
      assistant (PDA) to document clinical encounters and to retrieve patient safety
      related information at the point of care, and (2) enhancement of informatics
      competencies of students and faculty. These approaches may be useful to others
      wishing to promote patient safety through using informatics methods and
      technologies in healthcare curricula.

PMID- 15246039
TI  - Nursing curriculum and continuing education: future directions.
AB  - Redefinition of roles and functions in the healthcare systems of the future
      requires embracing to the value of continuing education. Within this framework
      healthcare professional education and continuing education, there are several
      core competencies described by Institute of Medicine (IOM) [A.C. Greiner, E.
      Knebel (Eds.), Health Professionals Education: Bridge to Quality, IOM, available
      at, May 2003] that form the foundation for practice for nurses and other
      healthcare professionals. An overarching sentence in the document says "All
      health professionals should be educated to deliver patient-centered care as
      members of an interdisciplinary team, emphasizing evidence-based practice,
      quality improvement approaches, and informatics" (p. 45). These IOM core
      competencies are: (1) Common value for respecting patients' differences, values,
      preferences and expressed needs. (2) Ability to cooperate, collaborate,
      communicate and integrate care using interdisciplinary teams. (3) Knowledge of
      and willingness to employ evidence-based practice principles. (4) Capability to
      apply quality and safety improvement approaches in care. (5) Understand, value
      and use informatics to all areas of health care, to reduce errors, manage
      knowledge and information, and make decisions and communicate. In enveloping
      these core competencies in basic and continuing education, it is necessary to
      build an evidence base for education itself, demand that faculty are prepared for
      the future. A crucial need is for healthcare professional students (including
      nursing students) learn interdisciplinary collaboration in the education of
      patients. A global strategy, using these competencies for preparing faculty is
      necessary; and some models already exist that can be further developed to meet
      future needs that are informatics driven in our increasingly technological future
      care systems.

PMID- 15246040
TI  - Protecting patient privacy by quantifiable control of disclosures in disseminated
      databases.
AB  - One of the fundamental rights of patients is to have their privacy protected by
      health care organizations, so that information that can be used to identify a
      particular individual is not used to reveal sensitive patient data such as
      diagnoses, reasons for ordering tests, test results, etc. A common practice is to
      remove sensitive data from databases that are disseminated to the public, but
      this can make the disseminated database useless for important public health
      purposes. If the degree of anonymity of a disseminated data set could be
      measured, it would be possible to design algorithms that can assure that the
      desired level of confidentiality is achieved. Privacy protection in disseminated
      databases can be facilitated by the use of special ambiguation algorithms. Most
      of these algorithms are aimed at making one individual indistinguishable from one
      or more of his peers. However, even in databases considered "anonymous", it may
      still be possible to obtain sensitive information about some individuals or
      groups of individuals with the use of pattern recognition algorithms. In this
      article, we study the problem of determining the degree of ambiguation in
      disseminated databases and discuss its implications in the development and
      testing of "anonymization" algorithms.

PMID- 15246041
TI  - Information technology and patient safety in nursing practice: an international
      perspective.
AB  - When people become patients, they place their trust in their health care
      providers. As providers assume responsibility for their diagnosis and treatment,
      patients have a right to expect that this will include responsibility for their
      safety during all aspects of care. However, increasing epidemiological data make
      it clear that patient safety is a global problem. Improved nursing care may
      prevent many adverse events, and nursing must take a stronger leadership role in
      this area. Although errors are almost inevitable, safety can be improved, and
      health care institutions are increasingly making safety a top priority.
      Information technology provides safety benefits by enhancing communication and
      delivering decision-support; its use will likely be a cornerstone for improving
      safety. This paper will discuss the status of patient safety from an
      international viewpoint, provide case studies from different countries, and
      discuss information technology solutions from a nursing perspective.

PMID- 15246042
TI  - Developing evidence-based interdisciplinary care standards and implications for
      improving patient safety.
AB  - AIM: Establish an organizational infrastructure to foster the delivery of quality
      clinical care through the development of interdisciplinary patient care standards
      that are evidenced-based and consistent throughout IHC. DESIGN: Develop a process
      for document development, review, and approval that includes best evidence from
      research and input from clinical experts. RESULTS: After six years of
      development, the electronic reference InfoBase (a searchable online reference
      manual which provides easy access to standards for clinical practice throughout
      the organization) contains over 700 interdisciplinary patient care standards
      (e.g., protocols, procedures, standards of care) and over 1000 "information
      chunks" (e.g., assessments, instructions, scales, tables, graphics) that support
      consistency in care delivery. All documents have been written, based on the best
      evidence available from research and reviewed by a group of clinicians at IHC
      facilities and approved for use throughout the company. An example of how
      standardization of interdisciplinary standards can improve patient safety in the
      area of falls is also included.

PMID- 15246043
TI  - Development of a compositional terminology model for nursing orders.
AB  - AIM: Develop a compositional terminology model for nursing orders that would
      conform to the existing standard health level seven (HL7) messaging standard for
      clinical orders. Develop and evaluate the set of attributes needed for a pre
      coordinated concept for a single nursing order, using a replicable three-step
      modeling process. RESULTS: A terminology model for nursing orders was developed
      using empirical data. The model was validated against nursing research and
      standards literature, and evaluated using 609 nursing orders that were
      successfully mapped to the structure. The representative services came from 20
      Intermountain Health Care (IHC) hospitals, demonstrating the generalizability of
      the model and its attributes across many care settings.

PMID- 15246044
TI  - Approach to mobile information and communication for health care.
AB  - Evidence suggests that inadequate access to information and ineffective
      communication are proximal causes of errors and other adverse events in-patient
      care. Within the context of reducing these proximal causes of errors, we explore
      the use of novel information-based approaches to improve information access and
      communication in health care settings. This paper describes the approaches for
      and the design of extensions to a clinical information system used to improve
      information access and communication at the point of care using information-based
      handheld wireless applications. These extensions include clinical and information
      resources, event monitoring, and a virtual whiteboard (VWB).

PMID- 15246045
TI  - Exploratory case method to determine the frequency of redundant orders within
      manually consolidated order lists.
AB  - A computerized provider order entry (CPOE) system can provide an efficient means
      of retrieving and consolidating order lists from multiple electronic clinical
      practice standards and protocols. However, the consolidated order list may
      contain exact duplicate or overlapping orders. Benner's framework for levels of
      nursing expertise can be used to explicate the variability of the nurse's
      responses to redundancies in order lists and the potential compromise to patient
      safety. An exploratory case method was performed to consolidate 74 orders from 11
      sources. The consolidated order list contained 35% fewer orders after the
      redundant orders were removed. Our work has shown that many redundant orders may
      arise by consolidating order lists from multiple electronic standards. It is
      imperative that consolidated electronic order lists be manageable by the nurse
      according to their level of clinical and computer expertise, and that redundant
      orders are resolved before being displayed to the nurse.

PMID- 15246046
TI  - Perception of disability in a public health perspective: a model based on fuzzy
      logic.
AB  - Measures of functional levels, commonly used to assess the safety and quality of
      life of individuals and populations, have not yet been derived from a fuzzy
      framework. The aim of this study is to estimate the degree of disability
      associated with varying functional levels, through a model based on fuzzy sets
      theory. A fuzzy linguistic model was developed to measure varying levels of
      functional disability, in accordance with the definitions of an individual's
      social and physical activities and mobility. One year of an adult's life whose
      mobility, social and physical activities were somewhat limited, was judged to be
      equivalent to 0.575 years free of functional disability. Results obtained from
      the fuzzy model approach those obtained with the quality of well-being scale
      (QWB), used as a conceptual framework. Such findings are encouraging, since the
      QWB is considered a consistent and valid approach for disability assessment and
      quality-of-life evaluation.

PMID- 15246047
TI  - Information technology as an infrastructure for patient safety: nursing research
      needs.
AB  - This article describes the process utilized to create research questions which
      promote technology as an infrastructure to enable safe nursing practice.
      Beginning with scenarios of safety problems related to nursing practice, the team
      identified information technology including hardware, software, and
      organizational and operational components to help improve the safety aspects
      addressed in the scenarios. Further discussed are characteristics of technology
      necessary at each step in the nursing process and finally recommendations are
      presented for various research questions that would be needed to enable research
      on the use of the proposed technologies.

PMID- 15246048
TI  - Chemokines in neoplastic progression.

PMID- 15246049
TI  - CCL2 (monocyte chemoattractant protein-1) and cancer.
AB  - Genetic analyses of cancer in humans indicate that chemokines and their receptors
      are unlikely to play direct roles in pathogenesis. However, these molecules have
      pleiotropic effects that impact on cancer pathobiology in animal models, and
      there is evidence that they may do the same in humans. Given their protean
      properties, chemokines could have tumor-promoting, tumor-suppressing activities,
      or either depending on context. An example is found in CCL2, a chemokine that
      attracts and activates mononuclear cells. In some settings, it stimulates host
      anti-tumor activities. However, tumor cells themselves secrete CCL2 suggesting
      that it has growth promoting effects. These have been documented in animal models
      and clinical epidemiological studies. If CCL2's protumorigenic activities can be
      validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer.

PMID- 15246050
TI  - Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors.
AB  - Leukocytes, and macrophages in particular, are an important component of the
      stroma of neoplastic tissues. Tumor-associated macrophages (TAM) have the
      properties of a polarized M2 population and are a key component of inflammatory
      circuits which promote tumor growth and progression. Chemokines play a key role
      in the recruitment and positioning of TAM and dendritic cells in tumors and
      contribute to shaping their functional properties. Chemokine-recruited and
      positioned tumor infiltrating leukocytes are a key component of inflammatory
      circuits which promote tumor progression.

PMID- 15246051
TI  - Regulation of the trafficking of tumour-infiltrating dendritic cells by
      chemokines.
AB  - To anticipate and initiate immune responses, dendritic cells follow a migratory
      route from their recruitment as sentinels into tissues, including solid tumors,
      then to secondary lymphoid organs where they profile the immune response.
      Migratory capacities--and especially chemokine responsiveness--are therefore key
      elements in dendritic cell biology. Here, we will review our current knowledge
      about tumour-infiltrating dendritic cells and the chemokine-driven migration
      flows in and out from tumors. Then we will discuss the consequences of the
      interactions between dendritic cells and tumors and the perspectives for
      translating our experimental knowledge of manipulating dendritic cell migratory
      flows into anti-cancer therapies.

PMID- 15246052
TI  - The significance of cancer cell expression of the chemokine receptor CXCR4.
AB  - Malignant cells from at least 23 different types of cancer express the chemokine
      receptor CXCR4 and respond to its ligand CXCL12. This receptor ligand pair
      appears to be involved in directed migration of cancer cells to sites of
      metastasis, increased survival of cancer cells in sub optimal conditions and
      establishment of a tumour promoting cytokine/chemokine network. Preliminary data
      from animal models suggest that CXCR4 may be an important therapeutic target in a
      range of cancers. However CXCR4 plays major roles in embryogenesis, homeostasis
      and inflammation. This raises questions concerning the specificity of CXCR4
      antagonists in the treatment of cancer.

PMID- 15246053
TI  - Chemokines in neoplastic progression.
AB  - Chemokines and their receptors have emerged as attractive targets regulating the
      migration of tumor cells in vivo, a process known as cancer metastasis. The
      control of metastasis is critical to the control of cancer progression. Two
      chemokine receptors and their ligands stand out as likely targets for
      therapeutics: CCR7/CCL21 for lymph node metastases, and CXCR4/CXCL12 for lung,
      liver, bone marrow, and brain metastases. The most widely expressed chemokine
      receptor among cancers is likely to be CXCR4.

PMID- 15246054
TI  - Chemokines and Kaposi's sarcoma.
AB  - Chemokines participate in many biological processes in homeostasis and disease.
      Recently, they have been implicated in cancer, more specifically in tumor
      angiogenesis and metastasis. Here we review evidence supporting a role for
      chemokines in the pathogenesis of Kaposi's sarcoma and discuss a possible role
      for these molecules in angioproliferation and immune evasion.

PMID- 15246055
TI  - CXC chemokines in angiogenesis of cancer.
AB  - The CXC chemokine family are unique cytokines known for their ability to have
      dual functions in the regulation of angiogenesis related to the following: (1)
      the presence or absence of the structural/functional motif (Glutamic acid-Leucine
      Arginine; 'ELR' motif) that immediately precedes the first cysteine amino acid
      residue in the primary structure of these chemokines; (2) interferon-inducible
      gene expression; and (3) specific receptor interaction on endothelial cells. In
      this review we will appraise the biology of these angiogenic and angiostatic CXC
      chemokines, and discuss their disparate angiogenic activity in the context of the
      pathogenesis of cancer.

PMID- 15246056
TI  - Chemokine-protease interactions in cancer.
AB  - Solid tumour and leukemic cells expressing chemokine receptors, metastasize to
      chemokine-secreting organs. Chemokines indirectly affect tumour development by
      attracting immunocompetent cells with pro- or anti-tumoral activities. Various
      membrane-associated and soluble proteases selectively cleave specific chemokines.
      Precursor plasma chemokines (CXCL7, CCL14) need to be proteolytically processed
      to obtain receptor affinity. Angiogenic CXC chemokines (CXCL1, CXCL8) have
      increased CXCR1/CXCR2 affinity after limited NH2-terminal processing, whereas
      truncated angiostatic chemokines (CXCL10) show lower CXCR3 affinity without loss
      of angiostatic potential. NH2-terminally cleaved monocyte chemotactic proteins
      (CCL2, CCL7, CCL8) have impaired capacity to attract tumour-associated
      macrophages and function as receptor antagonists for intact CC chemokines.
      Migration of Th1/CCR5+ and Th2/CCR4+ effector lymphocytes toward CCR5 (CCL5,
      CCL3L1) and CCR4 (CCL22) ligands is affected by cleavage. Although proteolytical
      processing of chemokines is well studied in vitro, the direct or indirect effects
      on tumour invasion and metastasis are only poorly evaluated.

PMID- 15246057
TI  - Cancer immunotherapy with chemoattractant peptides.
AB  - The chemokine/chemokine receptor network is an essential part of an intricate
      system of immunosurveillance and homeostasis, it promotes or suppresses
      neovascularization, affects and regulates directly or indirectly growth and
      metastasis of malignant cells. Numerous studies have been conducted to harness
      this network as therapeutic agents for cancer to redress the chemokine balance
      and control angiogenesis and tumour growth and metastasis. Second generation of
      immunotherapeutics and chemoattractant-based vaccines use chemokines and
      chemoattractant peptides to elicit antitumor immunity by a specific targeting and
      modulating subsets of effector leukocytes, including professional antigen
      presenting cells.

PMID- 15246058
TI  - Current models for starch synthesis and the sugary enhancer1 (se1) mutation in
      Zea mays.
AB  - Among the desirable quality traits essential for commercial production of fresh
      or processed sweet corn, kernel sugar content is universally important. In sweet
      corn genotypes the primary kernel sugar is sucrose, which is elevated at the
      expense of starch, particularly amylopectin. Sweet corn mutations have been
      traditionally divided into two classes. Generally speaking, class one mutations
      affect cytosolic reactions early in the process of starch synthesis, before
      starch is synthesized, and class two mutations affect reactions within the
      amyloplast directly involving starch granule assembly. Two widely used but
      previously unclassified mutations are sugary1 (su1) and sugary enhancer1 (se1).
      The se1 gene is a recessive modifier of su1; therefore, both genes require mutual
      discussion. This review provides current information about the su1 and se1 maize
      endosperm mutations and describes evidence further supporting previous
      suggestions that they fit criteria for categorization as class two mutants
      [Science 151 (1966) 341]. Information on the genetics and phenotype of se1 will
      be summarized and the hypothesized role of the se1 gene product discussed within
      the context of current models for starch synthesis in Zea mays L.

PMID- 15246059
TI  - New aspects of sterol biosynthesis in growth and development of higher plants.
AB  - The characterization of the enzymatic components of plant sterol biosynthesis,
      the phenotypic description of a set of Arabidopsis thaliana sterol mutants, and
      consequently, the identification of aspects of growth and development influenced
      by sterols have been in recent years a very fruitful area of research. The
      overall data obtained in the field have shown an essential role of sterols at the
      cellular level in hormone signaling, organized divisions and embryo patterning.
      Indeed, current research efforts strongly suggest that membrane bound proteins
      implicated in polarized auxin transport or ethylene signaling have altered
      activity or functionality in a modified sterolic environment.

PMID- 15246060
TI  - Posttranscriptional regulation of alpha-amylase II-4 expression by gibberellin in
      germinating rice seeds.
AB  - Hormonal regulation of expression of alpha-amylase II-4 that lacks the
      gibberellin-response cis-element (GARE) in the promoter region of the gene was
      studied in germinating rice (Oryza sativa L.) seeds. Temporal and spatial
      expression of alpha-amylase II-4 in the aleurone layer were essentially identical
      to those of alpha-amylase I-1 whose gene contains GARE, although these were
      distinguishable in the embryo tissues at the early stage of germination. The
      gibberellin-responsible expression of alpha-amylase II-4 was also similar to that
      of alpha-amylase I-1. However, the level of alpha-amylase II-4 mRNA was not
      increased by gibberellin, indicating that the transcriptional enhancement of
      alpha-amylase II-4 expression did not occur in the aleurone. Gibberellin
      stimulated the accumulation of 45Ca2+ into the intracellular secretory membrane
      system. In addition, several inhibitors for Ca2+ signaling, such as EGTA,
      neomycin, ruthenium red (RuR), and W-7 prevented the gibberellin-induced
      expression of alpha-amylase II-4 effectively. While the gibberellin-induced
      expression of alpha-amylase II-4 occurred normally in the aleurone layer of a
      rice dwarf mutant d1 which is defective in the alpha subunit of the
      heterotrimeric G protein. Based on these results, it was concluded that the
      posttranscriptional regulation of alpha-amylase II-4 expression by gibberellin
      operates in the aleurone layer of germinating rice seed, which is mediated by
      Ca2+ but not the G protein.

PMID- 15246061
TI  - Inhibition of cell-wall autolysis and pectin degradation by cations.
AB  - Modification of cell wall components such as cellulose, hemicellulose and pectin
      plays an important role in cell expansion. Cell expansion is known to be
      diminished by cations but it is unknown if this results from cations reacting
      with pectin or other cell wall components. Autolysis of cell wall material
      purified from bean root (Phaseolus vulgaris L.) occurred optimally at pH 5.0 and
      released mainly neutral sugars but very little uronic acid. Autolytic release of
      neutral sugars and uronic acid was decreased when cell wall material was loaded
      with Ca, Cu, Sr, Zn, Al or La cations. Results were also extended to a metal
      pectate model system, which behaved similarly to cell walls and these cations
      also inhibited the enzymatic degradation by added polygalacturonase (EC
      3.2.1.15). The extent of sugar release from cation-loaded cell wall material and
      pectate gels was related to the degree of cation saturation of the substrate, but
      not to the type of cation. The binding strength of the cations was assessed by
      their influence on the buffer capacity of the cell wall and pectate. The strongly
      bound cations (Cu, Al or La) resulted in higher cation saturation of the
      substrate and decreased enzymatic degradability than the weakly held cations (Ca,
      Sr and Zn). The results indicate that the junction zones between pectin molecules
      can peel open with weakly held cations, allowing polygalacturonase to cleave the
      hairy region of pectin, while strongly bound cations or high concentrations of
      cations force the junction zone closed, minimising enzymatic attack on the pectin
      backbone.

PMID- 15246062
TI  - Response of embryo axes of germinating seeds of yellow lupine to Fusarium
      oxysporum.
AB  - Defence responses of embryo axes of Lupinus luteus L. cv. Polo were studied 48-96
      h after inoculation with Fusarium oxysporum Schlecht f.sp. lupini. The infection
      restricted the growth of embryo axes, the lengths of infected embryo axes 72 and
      96 h after inoculation were 11 and 12 mm less in the controls, respectively,
      while their masses c. 0.03 g less than in the controls. The concentration of H2O2
      in embryo axes of inoculated germinating seeds was higher than in the control.
      This was probably a consequence of oxidative burst as well as H2O2 generation by
      the invading necrotrophic fungal pathogen. EPR-based analyses detected the
      presence of free radicals with g1 and g2 values of 2.0052 +/- 0.0004 and 2.0031
      +/- 0.0005, respectively. Concentrations of the radicals 72 and 96 h after
      inoculation were 50% higher than in the control. The values of the spectroscopic
      splitting coefficients suggest that they are quinone radicals. However,
      inoculated embryo axes possess a number of adaptive mechanisms protecting them
      from oxidative damage. A twofold increase in catalase (CAT, EC 1.11.1.6) activity
      was evidenced in embryo axes infected with F. oxysporum Schlecht f. sp. lupini,
      as compared to the control 48-96 h after inoculation. Superoxide dismutase (SOD,
      EC 1.15.1.1) activity 96 h after inoculation was 80% higher than in the control.
      Furthermore, EPR-based analyses revealed a higher concentration of Mn2+ ions
      after 72 h for inoculated embryo axes, as compared to the control. On the other
      hand, no increase was detected in the concentration of thiobarbituric acid
      reactive substances (products of lipid peroxidation) in infected embryo axes. The
      protective mechanisms induced in lupine embryo axes in response to F. oxysporum
      Schlecht f.sp. lupini were compared with responses to infections with pathogenic
      fungi elicited in other plant families.

PMID- 15246063
TI  - Protein composition of oil bodies in Arabidopsis thaliana ecotype WS.
AB  - Till now, only scattered data are available in the literature, which describes
      the protein content of plant oil bodies. Especially, the proteins closely
      associated with the model plant Arabidopsis thaliana oil bodies have never been
      previously purified and characterized. Oil bodies have been purified using
      flotation techniques, combined with incubations under high salt concentration, in
      the presence of detergents and urea in order to remove non-specifically trapped
      proteins. The identity and integrity of the oil bodies have been characterized.
      Oil bodies exhibited hydrodynamic diameters close to 2.6 microm, and a ratio
      fatty acid-protein content near 20. The proteins composing these organelles were
      extracted, separated by SDS-PAGE, digested by trypsin, and their peptides were
      subsequently analyzed by nano-chromatography-mass spectrometry (nano-LC-MS/MS).
      This led to the identification of a limited number of proteins: four different
      oleosins, ATS1, a protein homologous to calcium binding protein, a 11-beta
      hydroxysteroid dehydrogenase-like protein, a probable aquaporin and a
      glycosylphosphatidylinositol-anchored protein with no known function. The two
      last proteins were till now never identified in plant oil bodies. Structural
      proteins (oleosins) represented up to 79% of oil body proteins and the 18.5 kDa
      oleosin was the most abundant among them.

PMID- 15246064
TI  - Light and metabolic regulation of HAS1, HAS1.1 and HAS2, three asparagine
      synthetase genes in Helianthus annuus.
AB  - The role of light, carbon and nitrogen availability on the regulation of three
      asparagine synthetase (AS, EC 6.3.5.4)-coding genes, HAS1, HAS1.1 and HAS2, has
      been investigated in sunflower (Helianthus annuus). The response of each gene to
      different illumination conditions and to treatments that modify the carbon and
      nitrogen status of the plant was evaluated by Northern analysis with gene
      specific probes. Light represses the expression of HAS1 and HAS1.1. Phytochrome
      and photosynthesis-derived carbohydrates mediate this repression. On the
      contrary, maintained HAS2 expression requires light and is positively affected by
      sucrose. HAS1 and HAS1.1 expression is dependent on nitrogen availability, while
      HAS2 transcripts are still found in N-starved plants. High ammonium level induces
      all three AS genes and partially reverts sucrose repression of HAS1 and HAS1.1.
      In summary, light, carbon and nitrogen availability control asparagine synthesis
      in sunflower by regulating three AS-coding genes. Illumination and carbon
      sufficiency maintain HAS2 active to supply asparagine that can be used for
      growth. Darkness and low C/N ratio conditions trigger the response of the
      specialized HAS1 and HAS1.1 genes which contribute to store the excess nitrogen
      as asparagine. Ammonium induces all three AS-genes which may favor its
      detoxification.

PMID- 15246065
TI  - Hyperhydricity of Prunus avium shoots cultured on gelrite: a controlled stress
      response.
AB  - Hyperhydricity is a physiological disorder frequently affecting shoots
      vegetatively propagated in vitro. Hyperhydric shoots are characterised by a
      translucent aspect due to a chlorophyll deficiency, a not very developed cell
      wall and a high water content. Hyperhydricity of Prunus avium shoots was
      expressed in vitro in one multiplication cycle by replacing the gelling agent
      agar (normal shoots: NS) by gelrite (hyperhydric shoots: HS). P. avium shoots
      evolving towards the hyperhydric state produced higher amounts of ethylene,
      polyamines (PAs) and proline, which are substances considered as stress markers.
      A higher activity of glutathione peroxidase (GPX; EC 1.11.1.9), involved in
      organic hydroperoxide elimination, suggested an increased production of these
      compounds in HS. The unchanged free fatty acid composition indicated no HS
      membrane damages compared to NS. The ploidy level of HS nuclei was not affected,
      but the bigger size and the lower percentage of nuclei during the S phase
      suggested a slowing down of the cell cycle. The results argued for a stress
      response of the HS, but no signs of oxidative damages of lipid membrane and
      nucleus were observed. The discussion points out paradoxical results in a
      classical analysis of stress and suggests an alternative way of defense
      mechanisms in HS, involving homeostatic regulation and controlled degradation
      processes to maintain integrity and vital functions of the cell.

PMID- 15246066
TI  - Yeast hygromycin sensitivity as a functional assay of cyclic nucleotide gated
      cation channels.
AB  - Cyclic nucleotide gated cation channels (CNGCs) are a large (20 genes in
      Arabidopsis thaliana) family of plant ligand gated (i.e. cyclic nucleotides
      activate currents) ion channels, however, little is known about their functional
      properties. One reason for this is the recalcitrance of plant CNGC expression in
      heterologous systems amenable to patch clamp studies. Here, we show results
      demonstrating the efficacy of using growth of a K+ uptake-deficient yeast
      (trk1,2) as a functional assay of CNGCs as inwardly-conducting cell membrane
      cation (K+) transporters. Prior work demonstrated that trk1,2 is hypersensitive
      to the antibiotic hygromycin (hyg) and that expression of an inwardly conducting
      K+ transporter suppresses hyg hypersensitivity. We find that increasing [hyg] in
      solid YPD medium inhibits trk1,2 growth around a filter disk saturated with 3 M
      K+. Northern analysis indicated that message is transcribed in trk1,2 transformed
      with the CNGC coding sequences. Confocal imaging of yeast expressing CNGC
      fluorescent fusion proteins indicated channel targeting to the cell membrane.
      Trk1,2 expressing several plant CNGCs grown in the presence of hyg demonstrated
      (a) greater growth than trk1,2 transformed with empty plasmid, and (b) enhanced
      growth when cAMP was added to the medium. Alternatively, cAMP inhibited growth of
      yeast transformed with either the empty plasmid, or the plant K+ channel KAT1;
      this channel is not a CNGC. Growth of trk1,2 was dependent on filter disk [K+];
      suggesting that complementation of hyg hypersensitivity due to presence of a
      functional plant CNGC was dependent on K+ movement into the cytosol. We conclude
      that plant CNGC functional characterization can be facilitated by this assay
      system.

PMID- 15246067
TI  - Programmed cell death induces male sterility in Actinidia deliciosa female
      flowers.
AB  - The importance of programmed cell death (PCD) during the life cycle of plants is
      well established, although the underlying molecular mechanisms are still poorly
      defined. An emerging system for the study of PCD during development in plants is
      that of sex organ abortion. In this work we investigate the degeneration of
      microspores in the anthers of Actinidia deliciosa female flowers. The kiwifruit,
      A. deliciosa, is a dioecious species native to China. Pollen development in
      female flowers is equivalent to pollen development in the male flowers, until the
      microspores are released from the tetrads. At this time the first differences
      appear, and include the condensation and shrinkage of the cytoplasm, blebbing of
      the plasma membrane and of the nuclear envelope, and condensation of chromatin.
      However, at the time these events are occurring, all other cellular organelles,
      including mitochondria, have their structures well preserved. Fragmentation of
      DNA was detected in situ by the TUNEL procedure, which involves the end labeling
      of the DNA fragments by terminal deoxynucleotidyl transferase with UTP conjugated
      to a detectable marker. This assay confirmed the morphological characterization
      of PCD in this system.

PMID- 15246068
TI  - Methyl jasmonate promotes the transient reduction of the levels of 2-Cys
      peroxiredoxin in Ricinus communis plants.
AB  - Jasmonates are signaling molecules that play a key role in the regulation of
      metabolic processes, reproduction and defense against insects and pathogens. This
      study investigated the effects of methyl jasmonate on the protein pattern of
      Ricinus communis plants and the activity of guaiacol peroxidase, an antioxidant
      enzyme. Methyl jasmonate treatment caused a transient reduction in guaiacol
      peroxidase activity. A similar response was observed for the levels of 2-Cys
      peroxiredoxin protein. Moreover, the levels of the small and large chains of
      Rubisco were also reduced. The transient reduction of the levels and activity of
      antioxidant enzymes could account for the increase in the levels of H2O2, an
      important signaling molecule in plant defense.

PMID- 15246069
TI  - Response to ozone in two lettuce varieties on chlorophyll a fluorescence,
      photosynthetic pigments and lipid peroxidation.
AB  - The effect of different O3 concentrations on two lettuce (Lactuca sativa L.)
      varieties (Valladolid and Morella) was investigated through chlorophyll (Chl) a
      fluorescence parameters, photosynthetic pigments (Chl a, b and total carotenoid),
      lipid peroxidation and crop yield. Ozone fumigation caused: a decrease in maximum
      quantum yield of photosystem II (PSII) photochemistry (Fv/Fm) in mature leaves, a
      reduction in the non-cyclic electron flow (phiPSII) and a lower capacity to
      reoxidize the QA pool (qP). These reductions were significant in the Valladolid
      var. but not in the Morella var. A significant decrease in Chl a, b and in the
      total carotenoids was observed in the Valladolid var. but not in the Morella var.
      mainly under O3 fumigation conditions. We observed that the NPQ parameter did not
      increase in parallel to the qP reduction seen in the Valladolid var. O3
      fumigation with respect to air charcoal filtered air conditions. This fact could
      be associated with a lower capacity for dissipation of non-radiative excess
      energy and it may be closely correlated with significant decreases in
      photosynthetic pigment concentration. A decrease in NPQ from air ozone-free to
      ozone fumigation in the Morella var. can be explained by the need to maintain the
      photochemical quenching under O3 stress. It may also be associated with a slight
      increase in photosynthetic pigments. The differences between the two varieties
      may indicate that the Valladolid var. is more susceptible to O3 damage.

PMID- 15246070
TI  - Characterization of eight barley xantha-f mutants deficient in magnesium
      chelatase.
AB  - Magnesium chelatase (EC 6.6.1.1) catalyses the insertion of magnesium into
      protoporphyrin IX, the first unique step of the chlorophyll biosynthetic pathway.
      The enzyme is composed of three different subunits of approximately 40, 70 and
      140 kDa. In barley (Hordeum vulgare L.) the subunits are encoded by the genes
      Xantha-h, Xantha-g and Xantha-f. In the 1950s, eight induced xantha-f mutants
      were isolated. In this work we characterized these mutations at the DNA level and
      provided explanations for their phenotypes. The xantha-f10 mutation is a 3 bp
      deletion, resulting in a polypeptide lacking the glutamate residue at position
      424. The leaky mutation xantha-f26 has a missense mutation leading to a M632R
      exchange. The xantha-f27 and -f40 are deletions of 14 and 2 bp, respectively,
      resulting in truncated polypeptides of 1104 and 899 amino acid residues,
      respectively. Mutation xantha-f41 is an in-frame deletion that removes A439,
      L440, Q441 and V442 from the resulting protein. Mutation xantha-f58 is most
      likely a deletion of the whole Xantha-f gene, as no DNA fragments could be
      detected by PCR or southern blot experiments. The slightly leaky xantha-f60 and
      non-leaky -f68 mutations each have a missense mutation causing a P393L and G794E
      exchange in the polypeptide, respectively.

PMID- 15246071
TI  - Plant growth-promoting bacteria confer resistance in tomato plants to salt
      stress.
AB  - The object of the work is to evaluate whether rhizobacteria populating dry salty
      environments can increase resistance in tomato to salt stress. Seven strains of
      plant growth-promoting bacteria that have 1-aminocyclopropane-1-carboxylate (ACC)
      deaminase activity were isolated from soil samples taken from the Arava region of
      southern Israel. Following growth of these seedlings in the presence of 43 mM
      NaCl for 7 weeks, the bacterium that promoted growth to the greatest extent was
      selected for further study. DNA analysis of the 16S RNA indicated that the
      selected bacterium was Achromobacter piechaudii. This bacterium significantly
      increased the fresh and dry weights of tomato seedlings grown in the presence of
      up to 172 mM NaCl salt. The bacterium reduced the production of ethylene by
      tomato seedlings, which was otherwise stimulated when seedlings were challenged
      with increasing salt concentrations, but did not reduce the content of sodium.
      However, it slightly increased the uptake of phosphorous and potassium, which may
      contribute in part to activation of processes involved in the alleviation of the
      effect of salt. In the presence of salt the bacterium increased the water use
      efficiency (WUE). This may suggest that the bacterium act to alleviate the salt
      suppression of photosynthesis. However, the detailed mechanism was not
      elucidated. The work described in this report is a first step in the development
      of productive agricultural systems in saline environments.

PMID- 15246072
TI  - Synthesis and biological evaluation of novel T-type Ca2+ channel blockers.
AB  - A small molecule library of piperazinylalkylisoxazole derivatives containing
      about 600 compounds was designed, synthesized and evaluated for blocking effects
      on T-type Ca(2+) channel. Several ligands were identified to possess high
      inhibitory activity against the T-type Ca(2+) channel. The compound 21 with
      trifluoromethyl substituents at C(3)-position of phenyl group (R(1)) and C(2)
      position of phenyl group (R(2)) showed the highest inhibitory activity with
      IC(50) value of 1.02 microM, which is comparable to that of mibefradil.

PMID- 15246073
TI  - (E)- and (Z)-1,2,4-triazolylchromanone oxime ethers as conformationally
      constrained antifungals.
AB  - A series of 1,2,4-triazolylchromanone oxime ethers were synthesized and tested
      for in vitro antifungal activity. Many of these derivatives exhibit high activity
      against Candida albicans, Saccharomyces cerevisiae, Aspergillus niger and
      Microsporum gypseum.

PMID- 15246074
TI  - CoMFA and CoMSIA 3D QSAR analysis on N1-arylsulfonylindole compounds as 5-HT6
      antagonists.
AB  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) three-dimensional quantitative structure-activity
      relationship (3D-QSAR) studies were conducted on a series of N(1)
      arylsulfonylindole compounds as 5-HT(6) antagonists. Evaluation of 20 compounds
      served to establish the models. The lowest energy conformer of compound 1
      obtained from random search was used as template for alignment. The best
      predictions were obtained with CoMFA standard model (q2 = 0.643, r2 = 0.939 ) and
      with CoMSIA combined steric, electrostatic, hydrophobic, and hydrogen bond
      acceptor fields (q2 = 0.584, r2 = 0.902 ). Both the models were validated by an
      external test set of eight compounds giving satisfactory predictive r2 values of
      0.604 and 0.654, respectively. The information obtained from CoMFA and CoMSIA 3D
      contour maps can be used for further design of specific 5-HT(6) antagonists.

PMID- 15246075
TI  - Synthesis and in vitro antitumor activity of ring C and D-substituted
      phenanthrolin-7-one derivatives, analogues of the marine pyridoacridine alkaloids
      ascididemin and meridine.
AB  - A series of cycle C and D-substituted phenanthrolin-7-ones, analogues of the
      marine pyridoacridines meridine and ascididemin have been synthesized on the
      basis of Diels-Alder reactions involving quinoline-5,8-dione and 2- (or un)
      substituted-N,N-dimethylhydrazones. All the compounds were evaluated for in vitro
      cytotoxic activity against 12 distinct human cancer cell lines. They all exhibit
      cytotoxic activity with IC(50) values at least of micromolar order.

PMID- 15246076
TI  - Synthesis and binding properties of cyclopentane analogues of myo-inositol 1,4,5
      tris(phosphate).
AB  - Cyclopentanic analogues of myo-inositol 1,4,5-tris(phosphate) were synthesised
      starting from cyclopentadiene. The affinities of the trisphosphorylated
      derivatives for the Ins(1,4,5)P(3) receptors were equipotent to that of compound
      4, showing that the relative orientation of the functional groups, particularly
      of the hydroxyl, is not of prime importance in this series. The (31)P NMR
      titration curves show that the tris(phosphate) 5 behaves as the superimposition
      of an independent phosphate and a vicinal bis(phosphate).

PMID- 15246077
TI  - Synthesis and biological evaluation of bis and monocarbonate prodrugs of 10
      hydroxycamptothecins.
AB  - In an effort to improve the stability of labile lactone ring of camptothecins,
      the bis and mono-alkyl carbonate prodrugs of 10-hydroxycamptothecins were
      synthesized and their chemical and enzymatical stability as well as antitumor
      activity were studied. The in vitro evaluation of the stability of these
      carbonates indicates that the 10,20-biscarbonates are firstly hydrolyzed to
      afford the stable 20-monocarbonates. And the 10-carbonates are not stable in
      human plasma, mouse plasma and pH7.4 phosphate buffer, while the 20-carbonates
      are relatively stable in the three media and can be readily cleaved by porcine
      liver esterase. The overall toxicity of the tested carbonate against mice bearing
      S180 sarcoma is much lower when compared with the parent compound, and the
      antitumor activity is maintained.

PMID- 15246078
TI  - A QSAR study on inhibitory activities of 1-phenylbenzimidazoles against the
      platelet-derived growth factor receptor.
AB  - A quantitative structure-activity relationship (QSAR) study on inhibitory
      activities of 1-phenylbenzimidazoles against the platelet-derived growth factor
      receptor (PDGFR) was carried out in this work, and a QSAR model was developed. It
      gives an r2 of 0.78 for the training set of 55 active compounds, and an r2 of
      0.75 for the test set of 24 active compounds. The new model was further applied
      to predict inhibitory activities of additional 44 inactive compounds, and very
      good agreement with experimental observations was obtained. The new model
      requires only variable connectivity indices and two position indices as input
      parameters, which is simple and easy to apply. The new model is useful for
      developing new anticancer drugs, which also demonstrates that the recently
      developed variable connectivity indices are very useful structural descriptors in
      the QSAR studies in the fields of pharmaceutics and biochemistry.

PMID- 15246079
TI  - Inhibitory effects of multi-substituted benzylidenethiazolidine-2,4-diones on LDL
      oxidation.
AB  - Multi-substituted benzylidenethiazolidine-2,4-diones 3a-h were synthesized by
      Knoevenagel condensation of di- or tri-substituted 4-hydroxybenzaldehydes [or 1
      (3,5-di-tert-butyl-4-hydroxyphenyl)ethanone] 1 with thiazolidine-2,4-dione (2)
      and evaluated for antioxidant activities of Cu(2+)-induced oxidation of human low
      density lipoproteins (LDL). Among compounds 3a-h, 3a was superior to probucol in
      LDL-antioxidant activities and found to be ninefold more active than probucol.
      Due to its potency, compound 3a was tested for complementary in vitro
      investigations, such as TBARS assay (IC(50) = 0.1 microM), lag time (240 min at
      1.5 microM), relative electrophoretic mobility (REM) of ox-LDL (inhibition of 83%
      at 10 microM), fragmentation of apoB-100 (inhibition of 61% at 5 microM), and
      radical DPPH scavenging activity on copper-mediated LDL oxidation. In macrophage
      mediated LDL oxidation, the TBARS formation was also inhibited by compound 3a.

PMID- 15246081
TI  - Synthesis and evaluation of glycosidase inhibitory activity of octahydro-2H
      pyrido[1,2-a]pyrimidine and octahydro-imidazo[1,2-a]pyridine bicyclic
      diazasugars.
AB  - An efficient chiron approach for the synthesis of bicyclic diazasugars 4a and 4b
      having both -CH(2)OH and -OH functionality at the same carbon atom (C-6) is
      reported. Thus, easily available alpha-D-xylo-pentodialdo-1,4-furanose 5,
      obtained from D-glucose, on aldol-crossed Cannizzaro reaction followed by
      hydrogenolysis afforded 7. The regio-selective beta- and alpha-sulfonylation of
      hydroxymethyl groups in 7 afforded 8a (beta-sulfonylation) and 11 (alpha
      sulfonylation) in good yields. The cleavage of the 1,2-acetonide functionality,
      individually in 8a and 11, followed by reaction with ethylenediamine gave in situ
      formation of sugar aminals that undergo concomitant nucleophilic displacement of
      the sulfonyloxy group, by amino functionality, to give hitherto unknown bicyclic
      diazasugars 4a and 4b, respectively. The inhibitory potency of the earlier
      reported bicyclic diazasugars 3a,b and 4a,b was evaluated against alpha- and beta
      glycosidases and they were found to be potent and specific against the beta
      glycosidases with IC(50) and K(1) values in the micro molar range.

PMID- 15246080
TI  - Synthesis and biological evaluation of nonpeptide mimetics of omega-conotoxin
      GVIA.
AB  - A benzothiazole-derived compound (4a) designed to mimic the C(alpha)-C(beta) bond
      vectors and terminal functionalities of Lys2, Tyr13 and Arg17 in omega-conotoxin
      GVIA was synthesised, together with analogues (4b-d), which had each side-chain
      mimic systematically truncated or eliminated. The affinity of these compounds for
      rat brain N-type and P/Q-type voltage gated calcium channels (VGCCs) was
      determined. In terms of N-type channel affinity and selectivity, two of these
      compounds (4a and 4d) were found to be highly promising, first generation
      mimetics of omega-conotoxin. The fully functionalised mimetic (4a) showed low
      microM binding affinity to N-type VGCCs (IC(50)=1.9 microM) and greater than 20
      fold selectivity for this channel sub-type over P/Q-type VGCCs, whereas the
      mimetic in which the guanidine-type side chain was truncated back to an amine
      (4d, IC(50)= 4.1 microM) showed a greater than 25-fold selectivity for the N-type
      channel.

PMID- 15246082
TI  - Preparation and anti-HIV activities of retrojusticidin B analogs and azalignans.
AB  - Ten lignans (2-11) and a series of azalignans including 1-aryl-pyrronaphthalenes
      20-24 and 3-N-alkylaminomethyl-1-arylnaphthalenes 25-28, structurally related to
      two HIV reverse transcriptase inhibitors, retrojusticidin B and phyllamyricin A,
      were prepared from phyllanthin (1) for evaluation of anti-HIV activities. Anti
      HIV activity of these compounds on a R5 pseudotype virus, ConB/pNL43E-L+, in the
      U87-CD4-CCR5 cells has been measured. Compounds 5, 22, 23, and 28 showed good
      anti-HIV activity with IC(50) value of 0.25, 1.07, 0.01, 0.32 microg/mL,
      respectively.

PMID- 15246083
TI  - MAO inhibition by arylisopropylamines: the effect of oxygen substituents at the
      beta-position.
AB  - Twenty-nine arylisopropylamines, substituted at the beta-position of their side
      chain by an oxo, hydroxy, or methoxy group, were evaluated in vitro as MAO-A and
      MAO-B inhibitors. The oxo derivatives ('cathinones') were in general less active
      as MAO-A inhibitors than the corresponding arylisopropylamines, but exhibited an
      interesting MAO-B inhibiting activity, which was absent in the hydroxy, methoxy,
      and beta-unsubstituted analogues. These results suggest that selective affinity
      for the two MAO isoforms in this family of compounds is modulated not only by the
      aryl substitution pattern but also by the side-chain substituents on the
      arylalkylamine scaffold.

PMID- 15246085
TI  - Acid-base versus structural properties of an aminoglycoside antibiotic-
      sisomicin: NMR and potentiometric approach.
AB  - Aminoglycoside antibiotics constitute a class of the drugs of high interest,
      whose therapeutic action is based upon the electrostatic interaction with the
      variety of RNA molecules. The positive charge of these drugs molecules, located
      at their amino functions, has a prevailing influence on this process. The
      potentiometry and (1)H NMR spectroscopy are applied hereby to achieve the
      characteristics of the acid-base properties of particular protonating groups. We
      found that the pK values of deprotonation processes cover a wide values range 6
      9.8. The correlation spectra of sisomicin, both COSY and TOCSY, allowed
      attributing unambiguously individual signals to the corresponding protons. These
      spectra involve a lot of the cross-peaks originating from the B and C rings
      protons, while the analogous signals originating from A rings protons are less
      numerous. Molecular modeling provided that the methylated amino group of A ring
      is located too far from the protonated functions of the remaining rings to affect
      their pK values. The phenomena observed herein are discussed in line of strength
      of the analogous processes observed for other aminoglycosides. As the result,
      four types of amino groups consisted within these antibiotics are distinguished.

PMID- 15246084
TI  - A bacterial selection for the directed evolution of pyruvate aldolases.
AB  - A novel bacterial in vivo selection for pyruvate aldolase activity is described.
      Pyruvate kinase deficient cells, which lack the ability to biosynthetically
      generate pyruvate, require supplementation of exogenous pyruvate when grown on
      ribose. Supplementation with pyruvate concentrations as low as 50 microM rescues
      cell growth. A known substrate of the KDPG aldolases, 2-keto-4-hydroxy-4-(2'
      pyridyl)butyrate (KHPB), also rescues cell growth, consistent with retroaldol
      cleavage by KDPG aldolase and rescue through pyruvate release. An initial round
      of selection against 2-keto-4-hydroxyoctonate (KHO), a nonsubstrate for wild-type
      aldolase, produced three mutants with intriguing alterations in protein sequence.
      This selection system allows rapid screening of mutant enzyme libraries and
      facilitates the discovery of enzymes with novel substrate specificities.

PMID- 15246086
TI  - Substrate variants versus transition state analogues as noncovalent reversible
      enzyme inhibitors.
AB  - Reversible inhibitors are associated with fewer side effects than covalently
      binding ones and are, therefore, advantageous for treatment of conditions
      involving endogenous enzymes. Transition state analogue structures provide one
      design paradigm for such inhibitors; this paradigm seeks to exploit the
      capability of an enzyme active site to stabilise a transition state or associated
      intermediate. In contrast, structures that retain the functionality, and scissile
      bond of the substrate, can also act as reversible inhibitors; these are referred
      to here as substrate variants to distinguish them from substrate analogues. Their
      mode of inhibition depends on destabilisation of a reaction-path transition state
      or states. As the mode of destabilisation can be quite varied the scope to
      exploit substrate variants as reversible inhibitors is substantial. The two
      design paradigms are contrasted here and the case of substrate variants is
      delineated with a well-defined set of structures. These include the naturally
      occurring polypeptides BPTI (an inhibitor of a serine-based protease) and
      cathepsin propeptides (inhibitors of cysteine-based proteases) as well as the
      synthetic small-molecules cilastatin (an amide inhibitor of a zinc-based
      protease) and substituted mono- and tripeptides as inhibitors of cathepsins K and
      L.

PMID- 15246087
TI  - New orally active PDE4 inhibitors with therapeutic potential.
AB  - The design, synthesis, and biological evaluation of a series of pyrazolopyridines
      was carried out. Structural optimization of the aniline moiety of 4
      anilinopyrazolopyridine derivative 3a, which is one of the newly discovered
      chemical leads for PDE4 inhibitors from our in-house library, was performed
      successfully. The details of the discovery of new orally active PDE4 inhibitors,
      which are expected to show therapeutic potential, are presented and their
      structure-activity relationships are discussed. Pharmacological evaluation and
      pharmacokinetic data for representative compounds are also presented.

PMID- 15246088
TI  - 4,5-dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible
      nitric oxide synthase inhibitors.
AB  - In the course of our search for selective iNOS inhibitors, we have previously
      reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole
      derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS
      inhibitors, we focused our efforts on the synthesis and evaluation of the
      inhibitory activity against iNOS and selectivity for iNOS both in vitro and in
      vivo of a series of 2-imino-1,3-thiazolidine derivatives (3), which are analogues
      of 1 and 2. Our results show that among the compounds synthesized (4R,5R)-5-ethyl
      2-imino-4-methyl-1,3-thiazolidine [(4R,5R)-14a: ES-1537] exhibited potent
      inhibitory activity and selectivity for iNOS. In addition, ES-1537 had good
      pharmacokinetic profile in rats with BA value of 80%. It is therefore expected
      that ES-1537 may be therapeutically useful for the treatment of diseases related
      to excess production of NO.

PMID- 15246089
TI  - Synthesis and first in vivo evaluation of new selective high affinity beta1
      adrenoceptor radioligands for SPECT based on ICI 89,406.
AB  - The results of cardiac biopsies suggest that myocardial beta1-adrenoceptor (AR)
      density is reduced in patients with chronic heart failure, while changes in
      cardiac beta2-ARs vary. A technique for visualization and quantification of beta1
      AR populations rather than total beta-AR densities in the human heart would be of
      great clinical interest. Molecular imaging techniques, either single photon
      emission computed tomography (SPECT) or positron emission tomography (PET), with
      appropriate radiopharmaceuticals offer the possibility to assess beta-AR density
      noninvasively in humans, but to date, neither a SPECT nor a PET-radioligand is
      clinically established for the selective imaging of cardiac beta1-ARs. The aim of
      this study was to design a high affinity selective beta1-AR radioligand for the
      noninvasive in vivo imaging of cardiac beta1-AR density in man using SPECT. Based
      on the well-known selective beta1-AR antagonist, ICI 89,406, both the racemic
      iodinated target compound 11a and the (S)-enantiomer 15a were synthesized.
      Competition studies using the nonselective AR ligand, [(125)I]iodocyanopindolol
      ([(125)I]ICYP), and ventricular membrane preparations from mice showed that 11a
      and 15a possess higher beta1-AR affinities (up to 265-fold) and beta1-AR
      selectivities (up to 245-fold) than ICI 89,406. Encouraged by these results, the
      radioiodinated counterparts of racemic 11a (11b: (125)I, 11c: (123)I) and (S)
      configurated 15a (15b: (125)I, 15c: (123)I) were synthesized. The target
      compounds were evaluated in rats. Biodistribution and metabolism studies in rats
      indicated that there is a specific heart uptake of 11b-c and especially 15b-c
      accompanied by rapid metabolism of the radioligands. Therefore, radioiodinated
      11c and 15c appeared to be unpromising SPECT-radioligands for assessing beta1-ARs
      in vivo in the rat. However, the rat may metabolize beta-AR ligands more rapidly
      than other species as demonstrated for (S)-[(11)C]CGP 12177, a radioligand
      structurally related to 11a-c and 15a-c. Therefore further studies in a different
      animal model will be carried out.

PMID- 15246090
TI  - Drug design and synthesis of epsilon opioid receptor agonist: 17
      (cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan
      7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception
      mediated by putative epsilon opioid receptor.
AB  - Here we report the new drug design and synthesis of a series of 6,14
      endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid
      receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy
      3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N
      phenethyl)carboxamide (TAN-821), showed agonistic activity for a putative epsilon
      opioid receptor (IC(50) = 71.71nM) in the rat vas deferens (RVD) preparations.
      TAN-821 stimulated the binding of the nonhydrolyzable guanosine 5'-triphosphate
      analog, guanosine 5'-(gamma-thio)-triphosphate (GTPgammaS), to the mouse
      pons/medulla membrane via the activation of putative epsilon opioid receptor.
      Moreover, TAN-821 given intracerebroventricularly (i.c.v.) produced a marked
      antinociception in the tail-flick test (ED(50) = 1.73 microg) and the hot-plate
      test (ED(50) = 2.05 microg) in a dose-dependent manner. The antinociception
      induced by TAN-821 administered i.c.v. was blocked by the i.c.v.-pretreatment
      with a putative epsilon opioid receptor partial agonist beta-endorphin [1-27],
      but not a mu opioid receptor antagonist beta-FNA, a delta opioid receptor
      antagonist NTI, or a kappa opioid receptor antagonist nor-BNI. The present
      results suggest that TAN-821 may be a useful tool for the investigation on the
      pharmacological properties of the putative epsilon opioid receptor.

PMID- 15246091
TI  - Inhibitory mode of indole-2-carboxamide derivatives against HLGPa: molecular
      docking and 3D-QSAR analyses.
AB  - The interaction of a series of indole-2-carboxamide compounds with human liver
      glycogen phosphorylase a (HLGPa) have been studied employing molecular docking
      and 3D-QSAR approaches. The Lamarckian Genetic Algorithm (LGA) of AutoDock 3.0
      was employed to locate the binding orientations and conformations of the
      inhibitors interacting with HLGPa. The binding models were demonstrated in the
      aspects of inhibitor's conformation, subsite interaction, and hydrogen bonding.
      The very similar binding conformations of these inhibitors show that they
      interact with HLGPa in a very similar way. Good correlations between the
      calculated interaction free energies and experimental inhibitory activities
      suggest that the binding conformations of these inhibitors are reasonable. The
      structural and energetic differences in inhibitory potencies of indole-2
      carboxamide compounds were reasonably explored. Using the binding conformations
      of indole-2-carboxamides, consistent and highly predictive 3D-QSAR models were
      developed by CoMFA and CoMSIA analyses. The q2 values are 0.697 and 0.622 for
      CoMFA and CoMSIA models, respectively. The predictive ability of these models was
      validated by four compounds that were not included in the training set. Mapping
      these models back to the topology of the active site of HLGPa leads to a better
      understanding of the vital indole-2-carboxamide-HLGPa interactions. Structure
      based investigations and the final 3D-QSAR results provide clear guidelines and
      accurate activity predictions for novel inhibitor design.

PMID- 15246093
TI  - Synthesis of new 2-arylamino-6-trifluoromethylpyridine-3-carboxylic acid
      derivatives and investigation of their analgesic activity.
AB  - A new series of 2-arylamino-6-trifluoromethyl-3-carboxylic acid derivatives was
      synthesized and assayed in vivo for their analgesic properties by means of
      writhing test in rats. When compared to aspirin, ibuprofen and flufenamic acid
      some of the new compounds exhibited a comparable or improved analgesic activity
      and a lower ulcerogenic effect.

PMID- 15246092
TI  - Structure-activity relationships of seco-prezizaane and picrotoxane/picrodendrane
      terpenoids by Quasar receptor-surface modeling.
AB  - The seco-prezizaane-type sesquiterpenes pseudoanisatin and parviflorolide from
      Illicium are noncompetitive antagonists at housefly (Musca domestica) gamma
      aminobutyric acid (GABA) receptors. They show selectivity toward the insect
      receptor and thus represent new leads toward selective insecticides. Based on the
      binding data for 13 seco-prezizaane terpenoids and 17 picrotoxane and
      picrodendrane-type terpenoids to housefly and rat GABA receptors, a QSAR study
      was conducted by quasi-atomistic receptor-surface modeling (Quasar). The
      resulting models provide insight into the structural basis of selectivity and
      properties of the binding sites at GABA receptor-coupled chloride channels of
      insects and mammals.

PMID- 15246094
TI  - Synthesis and antimycobacterial activities of ring-substituted
      quinolinecarboxylic acid/ester analogues. Part 1.
AB  - Structural optimization of recently discovered new chemical entity, 2,8
      dicyclopentyl-4-methylquinoline (DCMQ; MIC= 6.25 microg/mL, M. tuberculosis
      H37Rv) resulted in the synthesis of four new series of ring-substituted
      quinolinecarboxylic acids/esters constituting 45 analogues. All new derivatives
      were evaluated for in vitro antimycobacterial activities against M. tuberculosis
      H37Rv. Certain ring-substituted-2-quinolinecarboxylic acid ester and ring
      substituted-2-quinoline acetic acid ester analogues described herein showed
      moderate to good inhibitory activity. In particular, three analogues methyl 4,5
      dicyclopentyl-2-quinolinecarboxylate (3b), methyl 4,8-dicyclopentyl-2
      quinolinecarboxylate (3c) and ethyl 2-(2,8-dicyclopentyl-4-quinolyl)acetate (14g)
      exhibited excellent MIC values of 1.00, 2.00 and 4.00microg/mL, respectively.
      Results obtained indicate that substitution of the quinoline ring with
      dicyclopentyl substituent presumably enhances the antimycobacterial activities in
      the quinoline analogues described herein.

PMID- 15246095
TI  - Synthesis of tetrahydronaphthyl thioureas as potent appetite suppressants.
AB  - A series of thiourea derivatives (7-23, 25-27) of 1-aminotetrahydronaphthalene
      (4) and 1-amino-2-hydroxytetrahydronaphthalene (5) were synthesized in single pot
      in 48-90% yield and evaluated for their anorexigenic activity. Among them
      compounds 10, 14, 15, 16 and 22 exhibited significant anorexigenic activity
      without any antidepressant effect and provided a new structural lead for appetite
      suppressants.

PMID- 15246096
TI  - Design, synthesis, biological evaluation and QSAR studies of novel
      bisepipodophyllotoxins as cytotoxic agents.
AB  - Two moieties of epipodophyllotoxin have been linked at C4-position to provide
      novel bisepipodophyllotoxin analogues. These have been evaluated for their
      anticancer potential and DNA-topoisomerase II poisoning activity. Most of these
      analogues have exhibited promising in vitro anticancer activity against different
      human tumour cell lines and interestingly 4(')-O-methylated analogues have shown
      increased cytotoxic activity. Similarly, the DNA-topo II poisoning activity
      tested for these compounds has not only exhibited the DNA cleavage potential
      comparable to etoposide, but for some compounds this cleavage potential is
      superior to etoposide. Further, an interesting structure-activity relationship of
      these epipodophyllotoxin dimers have been generated on the basis of GI(50)
      values. The equations indicated that GI(50) activity is strongly dependent on
      structural and thermodynamic properties. These QSAR results are discussed in
      conjunction with conformational analysis from molecular modelling studies. QSAR
      models developed in these studies will be helpful in the future to design novel
      potent bispodophyllotoxin analogues by minor structural modifications.

PMID- 15246097
TI  - New broad-spectrum parenteral cephalosporins exhibiting potent activity against
      both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas
      aeruginosa. Part 2: Synthesis and structure-activity relationships in the S-3578
      series.
AB  - Among the prepared novel cephalosporin derivatives related to S-3578, a series of
      7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-ethoxyiminoacetamido]-3-[1
      (aminoalkyl)-1H-pyrazolo[4,3-b]pyridinium-4-yl]methyl-3-cephem-4-carboxylate
      showed potent activity against both MRSA and Pseudomonas aeruginosa, and
      displayed good water solubility.

PMID- 15246098
TI  - New broad-spectrum parenteral cephalosporins exhibiting potent activity against
      both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas
      aeruginosa. Part 3: 7beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2
      ethoxyiminoacetamido] cephalosporins bearing 4-[3-(aminoalkyl)-ureido]-1
      pyridinium at C-3'.
AB  - Among the prepared C-3' substituted-pyridinium cephalosporins, a series of 7beta
      [2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido] cephalosporins bearing
      4-[3-(aminoalkyl)-ureido]-1-pyridinium at C-3' showed highly potent antibacterial
      activity against MRSA and Pseudomonas aeruginosa.

PMID- 15246099
TI  - DNG cytidine: synthesis and binding properties of octameric guanidinium-linked
      deoxycytidine oligomer.
AB  - The synthesis of guanidinium-linked cytidyl oligomer (DNG-C(8)), a cationic DNA
      analog, and the corresponding cytidine monomers is described. The DNG monomer
      synthesis was streamlined to produce a shorter route to the final monomer than
      previously reported for thymidine and subsequent solid-phase synthesis produced
      an octameric cytidyl DNG strand. Because octameric deoxyguanosine would be used
      as the complementary strand in our studies, it was necessary to investigate
      guanosine self-association. Singular value decomposition was used to
      mathematically deconvolve the spectral data and confirm the presence of
      transitions due to DNA-G(8) self-association. Job plots show the binding
      stoichiometry of DNG-C(8) with DNA-G(8) to be 1:1. Thermal denaturation studies
      of the DNG-C(8).DNA-G(8) duplex established a T(m) > or = 90 degrees and a DeltaG
      degree = -13.3 kcal mol(-1), indicating the DNG-C(8).DNA-G(8) duplex is over 1000
      times more stable than that of DNA-C(8).DNA-G(8).

PMID- 15246100
TI  - Novel imidazo[1,2-c]pyrimidine base-modified nucleosides: synthesis and antiviral
      evaluation.
AB  - The preparation of a series of novel 6-(beta-D-ribofuranosyl)-2-alkyl/aryl-6H
      imidazo[1,2-c]pyrimidin-5-one nucleosides and the 2-nitrile nucleosides, 6-(beta
      D-ribofuranosyl)-5-oxo-5,6-dihydro-imidazo[1,2-c]pyrimidine-2-carbonitrile and 2R
      and 2S isomers of 6-(beta-D-ribofuranosyl)-5-oxo-2,3,5,6-tetrahydro-imidazo[1,2
      c]pyrimidine-2-carbonitrile, is described using two synthetic approaches. The
      nucleoside mimetics described were evaluated against a wide range of viral types
      and strains in cell culture. With the exception of one nucleoside, which
      displayed anti-CMV activity at toxic concentrations, none of the compounds showed
      antiviral activity most likely due to a lack of substrate recognition by viral
      and/or cellular nucleoside kinases.

PMID- 15246101
TI  - Plant sterols as selective DNA polymerase beta lyase inhibitors and potentiators
      of bleomycin cytotoxicity.
AB  - In a survey of crude plant extracts for DNA polymerase beta lyase inhibitors, the
      hexanes extracts of Cladogynus orientalis, Hymenache donacifolia, and Heteropsis
      integerrima, and the methyl ethyl ketone extract of Acacia pilispina were found
      to exhibit good inhibition of the dRP lyase activity of DNA polymerase beta.
      Bioassay-guided fractionation of these extracts led to the isolation of three DNA
      polymerase beta lyase inhibitory phytosterols, namely stigmasterol (1) and beta
      sitosterol (2), isolated from the hexanes extracts, and beta-sitosterol-beta-d
      glucoside (3), isolated from the methyl ethyl ketone extract. Compounds 1-3
      inhibited the DNA polymerase beta lyase activity with IC(50) values of 43.6,
      43.3, and 72.4 microM, respectively. Compounds 1 and 2 were found capable of
      potentiating the action of bleomycin in cultured human tumor cells, consistent
      with the possibility that lyase inhibitors may find utility in vivo.

PMID- 15246102
TI  - Linckosides C-E, three new neuritogenic steroid glycosides from the Okinawan
      starfish Linckia laevigata.
AB  - Three new steroid glycosides, linckosides C-E, were isolated from the Okinawan
      starfish Linckia laevigata. Their structures and partial stereochemistry were
      elucidated by spectroscopic methods and chemical derivatization. These
      metabolites are additional members of the linckosides that were previously
      discovered as a novel class of neuritogenic compounds. Each of them possesses two
      monosaccharide units at C-3 of a polyhydroxylated steroidal aglycon and at the
      side chain (C-28 or C-29). Linckosides C and D are the first steroids that
      possess a hydroxyisopropyl substituent at C-24 of the side chain. These compounds
      are not only potent inducers of neurite outgrowth on PC12 cells but also
      significant enhancers of nerve growth factor (NGF) to induce the neurite
      outgrowth. The structure-activity relationships within the linckosides revealed
      that the presence of xylopyranose at the side chain was important rather than
      arabinofuranose, but that the diversity of the side chain carbon skeleton was
      not.

PMID- 15246103
TI  - Anti-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives.
AB  - A series of novel podophyllotoxin derivatives containing structural modifications
      at C-4 (7-14), C-4' (16-17), and the methylenedioxy A-ring (23-28) was
      synthesized and tested for inhibition of HIV replication. Four of these compounds
      (25-28) were previously reported to show EC(50) values of <0.001 microg/mL and
      therapeutic index (TI) values >120. Three of the newly tested compounds (8, 12,
      and 20) showed good activity with EC(50) values of 0.012, <0.001, and 0.389
      microg/mL and TI values of 19.1, >16, and 19.4, respectively. A comparison of the
      anti-HIV activity of these derivatives suggested that an opened A-ring with 6,7
      dimethoxy substitution and a 4'-demethylated E ring enhanced anti-HIV activity.

PMID- 15246104
TI  - Effect of stereochemistry on the anti-HIV activity of chiral thiourea compounds.
AB  - Chiral derivatives of several substituted halopyridyl and thiazolyl PETT
      compounds were synthesized as non-nucleoside inhibitors of the reverse
      transcriptase (RT) enzyme (NNRTI) of the human immunodeficiency virus (HIV-1).
      Molecular modeling studies indicated that because of the asymmetric geometry of
      the NNRTI binding pocket, the R stereoisomers would fit the NNRTI binding pocket
      of the HIV-1 RT much better than the corresponding S stereoisomers, as reflected
      by their 10(4)-fold lower K1 values. The R stereoisomers of several PETT
      derivatives inhibited recombinant RT in vitro with lower IC(50) values than their
      enantiomers. The active compounds were further evaluated for their ability to
      inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMC). All
      the R isomers once again showed potent anti-HIV activity and inhibited the
      replication of the HIV-1 strain HTLVIIIB in peripheral blood mononuclear cells
      (PBMC) at nanomolar concentrations whereas their enantiomers were substantially
      less potent. The lead compounds in the respective groups were further tested
      against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var
      (Y181C+K103N mutant) and RT MDR (V106N). The results showed that the lead
      compounds were several logs more potent than the standard NNRTI nevirapine.
      Structure-activity relationship studies also revealed a preference for the
      pyridyl unit with halo substitutions primarily at 5-position demonstrating the
      importance of regiochemistry. Our data provides experimental evidence that the
      stereochemistry as well as regiochemistry of NNRTI can profoundly affect their
      anti-HIV activity.

PMID- 15246105
TI  - 2-pyrones possessing antimicrobial and cytotoxic activities.
AB  - The 2-pyrone sub-unit is found in a number of natural products possessing broad
      spectrum biological activity. Such compounds are validated as being capable of
      binding to specific protein domains and able to exert a remarkable range of
      biological effects. In an effort to identify synthetic 2-pyrones with interesting
      biological effects, herein we report the synthesis and biological evaluation of 4
      substituted-6-methyl-2-pyrones. Synthetic routes to 4-alkyl/alkenyl/aryl/alkynyl
      6-methyl-2-pyrones have been developed utilising Sonogashira, Suzuki and Negishi
      cross-coupling starting from readily available 4-bromo-6-methyl-2-pyrone.
      Specific conditions for each organometallic protocol were required for successful
      cross-coupling. In particular, a triethylamine/acetonitrile--base/solvent mixture
      was crucial to Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone, whereas
      thallium carbonate was a mandatory base for the Suzuki cross-coupling of
      trialkylboranes. The 2-pyrones demonstrate potent inhibitory activity against
      Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Schizosaccharomyces
      pombe and Botrytis cinerea. The growth inhibitory activities of selected 2
      pyrones were determined in A2780 human ovarian carcinoma and K562 human chronic
      myelogenous leukaemia cell lines using an in vitro cell culture system (MTT
      assay). These studies demonstrate that 4-phenylethynyl-, 4
      tetrahydropyranylpropargyl ether- and 4-ethynyl-6-methyl-2-pyrones have excellent
      potential as a new class of anticancer agents.

PMID- 15246107
TI  - Epithelial cell motility on laminin-5: regulation by matrix assembly,
      proteolysis, integrins and erbB receptors.
AB  - Cell migration plays a central role in a wide variety of biological events,
      including embryogenesis, inflammatory immune response, wound healing, or cancer
      invasion. Tight regulation of cell motility is a prerequisite for normal
      development and maintenance of an organism, and to avoid metastatic spread of
      tumor cells. An important determinant of migratory efficiency is the substrate
      over which a cell migrates. Laminin-5 (Ln-5) is an extracellular matrix component
      prominent in basement membranes and as such it is a substrate in direct contact
      with epithelial cells. Interestingly, Ln-5 has been shown to both stimulate and
      downregulate epithelial cell migration. In this article, we plan to give an
      overview on the different mechanisms cells employ to regulate their migratory
      behavior on Ln-5. We will discuss how proteolytic processing of Ln-5 acts as
      posttranslational modification that plays a major role in the regulation of cell
      migration. The different proteolytic Ln-5 species may bind to distinct cell
      surface receptors called integrins, which translate substrate binding into a
      specific cellular response that triggers cell motility. Furthermore, interaction
      between Ln-5-binding integrins and other transmembrane and cytoplasmic proteins
      increases complexity and may allow fine-tuning of cell migration in response to
      the cellular environment.

PMID- 15246108
TI  - Identification of a functional CBF-binding CCAAT-like motif in the core promoter
      of the mouse pro-alpha 1(V) collagen gene (Col5a1).
AB  - We used structure-function analysis of the core promoter region to elucidate the
      transcriptional features of the mouse alpha 1(V) collagen gene (Col5a1). The core
      promoter, which lacks a typical TATA motif and has a high GC content, was defined
      within the 231 bp immediately upstream from the major transcription start site by
      transient transfection experiments. In this region, we identified three nuclear
      factor binding sites by electrophoretic mobility shift assay: BS1 (-195 to -167),
      BS2 (-134 to -106), and BS3 (-110 to -80). Oligonucleotide competition and
      supershift assays revealed that Sp1, CBF, and Sp1-related protein specifically
      bind to BS1, BS2, and BS3, respectively. The CCAAT-like motif, CAAAT, and
      flanking sequences are conserved between the mouse and human gene. CBF, which
      recognizes this motif, activated the Col5a1 promoter, as previously reported for
      Col1a1 and Col1a2. Furthermore, overexpression of a wild-type and mutant forms of
      CBF-B subunit altered this activity. These results suggest that CBF is a key
      factor in the coordinated expression of type I and V collagen genes.

PMID- 15246109
TI  - Structure, stability and interactions of type I collagen with GLY349-CYS
      substitution in alpha 1(I) chain in a murine Osteogenesis Imperfecta model.
AB  - Here we report the structural and functional studies of collagen from the Brtl
      mouse, a heterozygous knock-in model for Osteogenesis Imperfecta, which has a
      G349C substitution introduced in one col1a1 allele. We observed that 25+/-5% of
      alpha 1(I) chains in different tissues and in different extracts from matrix
      deposited by cultured cells were S-S-linked mutant dimers. Apparently mutant and
      normal molecules are equally well incorporated into the matrix and they form
      mature covalent crosslinks with the same efficiency. We found different extents
      of post-translational overmodification of mutant molecules in different tissues,
      but we found no consistent differences between lethal and non-lethal animals. We
      did not detect any changes in the thermal stability or rate of thermal
      denaturation of mutant collagen. We also did not detect any changes in collagen
      collagen recognition and interactions except for disruption of quasi-crystalline
      lateral packing of molecules in tendons from some, mostly prepubertal, mutant
      animals. In contrast, alpha 1(I)(3) collagen from the oim mouse--the only other
      non-lethal murine OI model studied by similar techniques--has altered stability,
      fibrillogenesis, collagen-collagen interactions and produces a more consistent
      and more pronounced disruption of tendon crystallinity. Nevertheless, while the
      G349C substitution causes moderate or lethal OI, heterozygous oim mice are much
      less affected. Overall, our results suggest that OI symptoms and phenotype
      variation in G349C animals are related to abnormal interactions of mutant
      collagen helices with other matrix molecules or abnormal function of osteoblasts
      rather than to abnormal structure, physical properties or interactions between
      mutant collagen helices.

PMID- 15246110
TI  - Comparative study of cellular and extracellular matrix composition of native and
      tissue engineered heart valves.
AB  - Tissue engineering of heart valves utilizes biodegradable or metabolizable
      scaffolds for remodeling by seeded autologous cells. The aim of this study was to
      determine and compare extracellular matrix (ECM) formations, cellular phenotypes
      and cell location of native and tissue engineered (TE) valve leaflets. Ovine
      carotid arteries, ovine and porcine hearts were obtained from slaughterhouses.
      Cells were isolated from carotid arteries and dissected ovine, porcine and TE
      leaflets. TE constructs were fabricated from decellularized porcine pulmonary
      valves, seeded ovine arterial cells and subsequent 16 days dynamic in vitro
      culture using a pulsatile bioreactor. Native and TE valves were studied by
      histology (hematoxylin-eosin, resorcin-fuchsin, Movat pentachrome), NIR
      femtosecond multiphoton laser scanning microscopy and scanning electron
      microscopy (SEM). Cells of native and TE tissues were identified and localized by
      immunohistochemistry. Arterial, valvular and re-isolated TE-construct cells were
      processed for immunocytochemistry and Western blotting. ECM analysis and SEM
      revealed characteristical and comparable structures in native and TE leaflets.
      Most cells in native leaflets stained strongly positive for vimentin. Cells
      positive to alpha-smooth muscle actin (alpha-SMA), myosin and calponin were only
      found at the ventricular (inflow) side of ovine aortic and porcine pulmonary
      valve leaflets. Cells from TE constructs had a strong expression of vimentin,
      alpha-SMA, myosin, calponin and h-caldesmon throughout the entire leaflet.
      Comparable ECM formation and endothelial cell lining of native and TE leaflets
      could be demonstrated. However, immunostaining revealed significant differences
      between valvular cell phenotypes of native and TE leaflets. These results may be
      essential for further cardiovascular tissue engineering efforts.

PMID- 15246111
TI  - Characterisation of proteoglycans and their catabolic products in tendon and
      explant cultures of tendon.
AB  - Tendons are collagenous tissues made of mainly Type I collagen and it has been
      shown that the major proteoglycans of tendons are decorin and versican. Little is
      still known about the catabolism of these proteoglycans in tendon. Therefore, the
      aim of the study was to characterise the proteoglycans including their catabolic
      products present in uncultured bovine tendon and in the explant cultures of
      tendon. In this study, the proteoglycans were extracted from the tensile region
      of deep flexor tendon and isolated by ion-exchange chromatography and after
      deglycosylation analysed by SDS-polyacrylamide electrophoresis, Western blotting
      and amino-terminal amino acid sequence analysis. Based on amino acid sequence
      analysis, approximately 80% of the total proteoglycan core proteins in fresh
      tendon was decorin. Other species that were detected were biglycan and the large
      proteoglycans versican (splice variants V(0) and/or V(1)) and aggrecan.
      Approximately 35% of decorin present in the matrix showed carboxyl-terminal
      proteolytic processing at a number of specific sites. The analysis of small
      proteoglycans lost to the medium of tendon explants showed the presence of
      biglycan and decorin with the intact core protein as well as decorin fragments
      that contained the amino terminus of the core protein. In addition, two core
      protein peptides of decorin starting at residues K(171) and D(180) were observed
      in the matrix and one core protein with an amino-terminal sequence commencing at
      G(189) was isolated from the culture medium. The majority of the large
      proteoglycans present in the matrix of tendon were degraded and did not contain
      the G1 globular domain. Furthermore the aggrecan catabolites present in fresh
      tendon and lost to the medium of explants were derived from aggrecanase cleavage
      of the core protein at residues E(373)-A(374), E(1480)-G(1481) and E(1771)
      A(1772). The analysis of versican catabolites (splice variants V(0) and/or V(1))
      also showed evidence of degradation of the core protein by aggrecanase within the
      GAG-beta subdomain, as well as cleavage by other proteinase(s) within the GAG
      alpha and GAG-beta subdomains of versican (variants V(0) and/or V(2)).
      Degradation products from the amino terminal region of type XII collagen were
      also detected in the matrix and medium of tendon explants. This work suggests a
      prominent role for aggrecanase enzymes in the degradation of aggrecan and to a
      lesser extent versican. Other unidentified proteinases are also involved in the
      degradation of versican and small leucine-rich proteoglycans.

PMID- 15246112
TI  - Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and
      hippocampus of temporal lobe epilepsy patients.
AB  - RATIONALE: Altered expression of glutamate transporter EAAT2 protein has been
      reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two
      alternative EAAT2 mRNA splice forms, one resulting from a partial retention of
      intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously
      implicated in the loss of EAAT2 protein in patients with amyotrophic lateral
      sclerosis. METHODS: By RT-PCR we studied the occurrence of I7R and E9S in
      neocortical and hippocampal specimens from TLE patients and non-neurological
      controls. RESULTS: Both splice forms were found in all neocortical specimens from
      TLE patients (100% I7R, 100% E9S). This was significantly more than in controls
      (67% I7R, 60% E9S; P < 0.05). We also detected I7R and E9S in all seven motor
      cortex post-mortem samples from patients with amyotrophic lateral sclerosis.
      Within the TLE patient group, both splice variants appeared significantly more in
      non-sclerotic (100%), than in sclerotic hippocampi (69%, P < 0.05). CONCLUSION:
      These data indicate that the epileptic brain, especially that of TLE patients
      without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA
      splicing. Our data confirm that the presence of alternative EAAT2 splice forms is
      not disease specific.

PMID- 15246113
TI  - The A3 adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform
      discharges in the CA3 area of immature rat hippocampal slices.
AB  - The effects of the A(3) adenosine receptor agonist 2-Cl-IB-MECA were tested on
      epileptiform field potentials recorded in the CA3 area of postnatal days 10-20
      immature hippocampal slices, during perfusion with the GABA(A) receptor
      antagonist bicuculline (10 microM). Evoked potentials: 2-Cl-IB-MECA (1-50 microM,
      n = 17) had consistently excitatory effects, blocked by the A(3) receptor
      antagonist MRS 1220 (1 microM, n = 7), but not occluded in the presence of the
      A(1) antagonist DPCPX (1 microM, n = 12) or the A(2A) antagonist ZM-241385 (0.1
      microM, n = 12). 2-Cl-IB-MECA reversed the inhibitory effects (n = 5) of the
      adenosine uptake blocker nitrobenzylthioinosine (NBTI, 50 microM), but did not
      increase its excitatory effects (n = 19). Spontaneous discharges: 2-Cl-IB-MECA (1
      microM) induced them or increased their frequency in 14/30 slices, an effect
      reversed by MRS 1220 (n = 3), and observed also following pre-perfusion with
      DPCPX (n = 11), ZM-241385 (n = 11) or both (n = 10). In the presence of the A(1)
      antagonist DPCPX, NBTI increased the frequency of spontaneous discharges, an
      effect partially reversed by MRS 1220 (n = 8), thus suggesting that a rise in
      endogenous adenosine during disinhibition may activate A(3) receptors. In
      conclusion, these findings suggest strongly that activation of A(3) receptors,
      following a rise in endogenous adenosine (i.e. during seizures, hypoxia),
      facilitates excitation, thus limiting the known inhibitory and/or neuroprotective
      effects of adenosine in immature brain.

PMID- 15246114
TI  - Low frequency stimulation modifies receptor binding in rat brain.
AB  - Experiments were designed to reproduce the antiepileptic effects of low frequency
      stimulation (LFS) during the amygdala kindling process and to examine LFS-induced
      changes in receptor binding levels of different neurotransmitters in normal
      brain. Male Wistar rats were stereotactically implanted in the right amygdala
      with a bipolar electrode. Rats (n = 14) received twice daily LFS (15 min train of
      1Hz, 0.1 ms at an intensity of 100 to 400 microA) immediately after amygdala
      kindling stimulation (1s train of 60 Hz biphasic square waves, each 1 ms at
      amplitude of 200-500 microA) during 20 days. The LFS suppressed epileptogenesis
      (full attainment of stage V kindling) but not the presence of partial seizures
      (lower stages of kindling) in 85.7% of the rats. Thereafter, normal rats (n = 7)
      received amygdala LFS twice daily for 40 trials. Animals were sacrificed 24 h
      after last stimulation and their brain used for labeling mu opioid,
      benzodiazepine (BZD), alpha(1)-adrenergic, and adenylyl cyclase binding.
      Autoradiography experiments revealed increased BZD receptor binding in
      basolateral amygdala (20.5%) and thalamus (29.3%) ipsilateral to the place of
      stimulation and in contralateral temporal cortex (18%) as well as decreased
      values in ipsilateral frontal cortex (24.2%). Concerning mu receptors, LFS
      decreased binding values in ipsilateral sensorimotor (7.2%) and temporal (5.6%)
      cortices, dentate gyrus (5.8% ipsi and 6.8% contralateral, respectively), and
      contralateral CA1 area of dorsal hippocampus (5.5%). LFS did not modify alpha(1)
      receptor and adenylyl cyclase binding values. These findings suggest that the
      antiepileptic effects of LFS may involve activation of GABA-BZD and endogenous
      opioid systems.

PMID- 15246115
TI  - Distinct electrophysiological alterations in dentate gyrus versus CA1 glial cells
      from epileptic humans with temporal lobe sclerosis.
AB  - Previous studies have characterized the electrophysiological properties of
      astrocytes in the CA1 region of hippocampi resected from patients with
      intractable temporal lobe epilepsy (TLE). However, the properties of hilar
      astrocytes from such patients have not been studied although astrocytes display
      regional heterogeneity and a non-uniform response to injury. Thus, we performed
      patch-clamp recordings of putative astrocytes in hilar and CA1 regions of
      surgically removed epileptic hippocampi with and without sclerosis (mesial TLE,
      MTLE patients, and paradoxical TLE, PTLE patients, respectively), and non
      epileptic, non-sclerotic hippocampi (tumor patients). Our data show that the
      current profile of hilar astrocytes undergoes significant changes in MTLE but not
      in PTLE or tumor hippocampi. In particular, inwardly rectifying K(+) (K(IR)) and
      outwardly rectifying K(+) currents were reduced, inward Na(+) currents and
      membrane resistances were increased in putative astrocytes from MLTE cases
      compared to PTLE and tumor cases. Because the conductance of K(IR) channels in
      cell-attached patches (approximately 34pS) from MTLE tissue was not altered, a
      reduction in the number of K(IR) channels likely accounts for the decrease in
      whole-cell K(IR) conductance. Presumed astrocytes in the CA1 region from each
      patient group displayed intercellular coupling and a passive current profile;
      these characteristics were never observed in hilar glial cells. No apparent
      changes in the current profile of coupled CA1 glial cells could be detected
      between MTLE, PTLE and tumor tissues. Additionally, CA1 glial cells expressed a
      high density of 34pS K(IR) channels. These data suggest that K(+) buffering via
      K(IR) channels may be functionally compromised in hilar astrocytes of epileptic
      and sclerotic (MTLE) human hippocampi. By contrast, CA1 astrocytes retained their
      intercellular coupling and K(IR) channel expression necessary for K(+) buffering.

PMID- 15246116
TI  - "Tectonic" hippocampal malformations in patients with temporal lobe epilepsy.
AB  - Histological analysis of hippocampi removed en bloc during surgical treatment of
      temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of
      the CA1 pyramidal cell/subicular layers that were consistently accompanied by
      "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi
      containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus
      exhibited minor cell loss compared to hippocampi with typical hippocampal
      sclerosis, and retrospective analysis revealed that conventional imaging methods
      usually failed to detect subtle hippocampal atrophy or abnormal signal
      characteristics in patients with this anomaly. Cells within the anomaly exhibited
      the spherical appearance of undifferentiated pyramidal layer neurons, and were
      immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic
      marker beta-synuclein suggested abnormal dentate gyrus lamination in segments
      containing the pyramidal cell layer anomaly, but not in unaffected areas of the
      same specimens. Despite differences in the extent of neuronal loss between
      patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the
      incidence of antecedent febrile seizures was similar in both groups. In a
      comparison group of hippocampi obtained at autopsy, structural irregularities
      were evident, but were consistently less disruptive to hippocampal architecture
      than the anomalies observed in epilepsy patients. We hypothesize that
      developmental malformation of the CA1 pyramidal cell/subicular layers may
      adversely influence the subsequent development of the adjacent dentate gyrus, and
      may render temporal lobe structures hyperexcitable and more vulnerable to
      relatively innocuous seizures and injuries. Thus, these presumably developmental
      hippocampal anomalies may serve as substrates for early febrile seizures and
      subsequent epilepsy.

PMID- 15246117
TI  - Influence of aging on serum phenytoin concentrations: a pharmacokinetic analysis
      based on therapeutic drug monitoring data.
AB  - The influence of aging on the pharmacokinetics of phenytoin at steady-state was
      evaluated retrospectically by comparing apparent oral clearance values (CL/F) in
      75 patients aged 65-90 years (mean, 71.7 +/- 5.3 years) receiving phenytoin alone
      (n = 58) or in combination with phenobarbital (n = 17) and in an equal number of
      control patients aged 20-50 years (mean, 36.7 +/- 8.5 years) matched for gender,
      body weight, and comedication. All data were derived from the database of the
      therapeutic drug monitoring service (TDMS) of an academic neurological hospital.
      On average, elderly patients were found to exhibit slightly higher CL/F values
      compared with controls (14.6 +/- 4.7 ml h(-1) kg(-1) versus 13.1 +/- 4.2 ml h(-1)
      kg(-1), P < 0.05), the difference being probably related to the dose-dependent
      nature of phenytoin metabolism and the fact that elderly patients received lower
      dosages (4.4 +/- 1.1 mg kg(-1)day(-1) versus 5.3 +/- 1.1 mg kg(-1) day(-1), P <
      0.001) and had lower serum phenytoin concentrations (14.1 +/- 5.7 microg ml(-1)
      versus 18.6 +/- 6.8 microg ml(-1), P < 0.0001). Gender and phenobarbital
      comedication were not found to exert any statistically significant influence on
      phenytoin CL/F. By contrast, in the elderly group, CL/F values were negatively
      correlated with age. On average, CL/F values decreased by about one-third between
      65 and 85 years of age, but interindividual variability was considerable and age
      explained only 7.8% of the variation in CL/F in the elderly group. Overall, these
      findings indicate that aging is associated with a progressive decline in
      phenytoin clearance, presumably as a result of decreased drug metabolizing
      capacity. Because assessment was based on total serum phenytoin concentrations
      and the unbound fraction of phenytoin is known to decrease in old age, the
      influence of aging as quantified in this study may underestimate the magnitude of
      changes in the clearance of unbound, pharmacologically active drug. Based on
      these data, it is prudent to utilize initially smaller phenytoin dosages in old
      patients, and to make subsequent dose adjustments based on clinical response and
      serum drug level measurements. Interpretation of the latter, however, should take
      into account the possibility of an increase in the fraction of unbound drug.

PMID- 15246119
TI  - Effects of the combination of valproate and ethosuximide on spike wave discharges
      in WAG/Rij rats.
AB  - OBJECTIVE: We studied the interaction between valproate (VPA) and ethosuximide
      (ESM) in diminishing the incidence of absence-like spike-wave discharges (SWDs)
      in the EEG of WAG/Rij rats. METHODS: VPA, ESM, their combination and saline were
      evaluated in 16 rats. The doses of VPA ranged from 0 to 280 mg/kg and the doses
      of ESM ranged from 0 to 40 mg/kg. For the drug combination, a fixed weight ratio
      of 7/1 VPA/ESM was used. The incidence of SWDs in the EEG was determined for the
      period of 15-75 min after injection and compared to the incidence of SWDs prior
      to injection. The sigmoid-E(max) equation was fitted to the data. Isobolic
      analysis, on 50% effect, was used to assess the character of the drug
      interaction. RESULTS: The parameters for diminishing the incidence of the SWDs
      were: VPA: ED(50): 121mg/kg; ESM: ED(50): 21.5mg/kg; VPA/ESM: ED(50): 112/16
      mg/kg. Isobolic analysis showed that a higher drug load was needed of the
      combination than of the individual drugs to achieve a 50% reduction of SWDs:
      factor 1.67; P = 0.012. CONCLUSION: The interaction between valproate and
      ethosuximide was shown to be infra-additive in diminishing the incidence of SWDs
      in WAG/Rij rats.

PMID- 15246118
TI  - Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial
      temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status
      epilepticus.
AB  - A comparative study of the expression of metabotropic glutamate receptor 2/3
      (mGluR2/3) was done in the hippocampus of rats and mice after pilocarpine-induced
      status epilepticus (APISE), and of patients with mesial temporal lobe epilepsy.
      At 1 day APISE, there was a marked increase in mGluR2/3 immunoreactivity in the
      stratum lacunosum moleculare (SLM) of CA1 area and in the middle one-third of the
      molecular layer (MM) of the dentate gyrus. Immuno-electron microscopic study
      showed degenerating mGluR2/3 positive axons in the SLM of CA1 area at 1 day
      APISE. From 7 days, mGluR2/3 immunopositive product decreased, and by 31 days
      APISE, it almost disappeared in two-thirds of the SLM near CA2. In the mouse
      model at 2 months APISE, mGluR2/3 immunopositive product in two-thirds of the SLM
      near the stratum radiatum disappeared, and so did in the whole SLM of CA1 area in
      patients with mesial temporal lobe epilepsy. Neuropharmacological study by
      intravenous injection of mGluR2/3 agonist 2R,4R-4-aminopyrrolidine-2,4
      dicarboxylate [(2R,4R)-APDC] at different doses at 1h during pilocarpine induced
      status epilepticus showed that (2R,4R)-APDC could not stop seizures and neuronal
      death in the hilus of the dentate gyrus. The present study, therefore, suggests
      that the reduction of mGluR2/3 immunopositive product in the SLM of CA1 is a
      consequence of neuronal loss in either the entorhinal cortex or CA1 area of the
      hippocampus, and at the dosage range from 12.5 to 600 mg/kg, (2R,4R)-APDC may not
      be effective in the prevention of seizures or neuronal death in the hilus of the
      dentate gyrus.

PMID- 15246120
TI  - Acute vagus nerve stimulation does not suppress spike and wave discharges in
      genetic absence epilepsy rats from Strasbourg.
AB  - We evaluated the efficacy of vagus nerve stimulation (VNS) in Genetic Absence
      Epilepsy Rats from Strasbourg (GAERS), a validated model for absence epilepsy. In
      the first experiment, we investigated whether VNS applied at seizure onset can
      interrupt spike and wave discharges (SWD). In the second experiment, we
      investigated whether SWD are suppressed or shortened in duration when VNS is
      applied several hours per day. Both control and VNS groups underwent EEG and VNS
      electrode implantation. For the first experiment, a randomized crossover design
      was used. Stimuli (amplitude: 3 V; frequency: 30 Hz; pulse duration: 500 micros)
      were given when an SWD occurred on the EEG. The experiment was repeated the next
      day. In the second experiment, treated animals were stimulated (amplitude: 1.5
      mA; frequency: 30 Hz; pulse duration: 500 micros; on/off time cycle: 30 s / 5
      min) for 3h per day, during five consecutive days. In the first experiment, the
      duration of the SWD was increased on day 1, (P < 0.05). There was no difference
      in SWD duration on Day 2. In the second experiment, no significant differences
      could be found in number, duration and EEG frequency of SWD. VNS applied at the
      onset of an SWD can prolong the duration of SWD in GAERS. As a 5-day stimulation
      protocol had no effect, long-term VNS might be necessary to affect SWD.

PMID- 15246122
TI  - Blinding was judged more difficult to achieve and maintain in nonpharmacologic
      than pharmacologic trials.
AB  - OBJECTIVE: To compare the feasibility of blinding and the perceived risk of
      unblinding in trials evaluating pharmacologic (PT) and nonpharmacologic
      treatments (NPT) of hip or knee osteoarthritis. STUDY DESIGN AND SETTING: Two
      independent reviewers assessed the feasibility of blinding patients, care
      providers, and outcome assessors, the perceived risk of unblinding, and whether
      blinding was reported in 110 reports of randomized controlled trials (RCTs)
      evaluating PT and NPT in patients with hip or knee osteoarthritis. RESULTS:
      Blinding was considered to be possible less often in NPT trials than in PT trials
      for patients (42 vs. 96%; P <.001), care providers (12 vs. 96%; P <.001), and
      outcome assessors (34 vs. 98%; P <.001). When blinding was judged feasible, the
      perceived risk of unblinding was more often considered moderate or important in
      NPT than PT trials for patients (35 vs. 14%, P=.02) and outcome assessors (44 vs.
      10%, P=.0004). When blinding was judged feasible, it was reported less often in
      NPT reports than in PT reports for patients (46 vs. 98%, P <.001), care providers
      (43 vs. 83%, P=.03), and outcome assessors (72 vs. 98%, P=.0006). CONCLUSION:
      Blinding appears to be more difficult to achieve and unblinding may occur more
      often in NPT than PT trials.

PMID- 15246121
TI  - The balance of inhibitory and excitatory cytokines is differently regulated in
      vivo and in vitro among therapy resistant epilepsy patients.
AB  - PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine
      expression. In this study we investigated cytokine production in circulating
      blood and peripheral blood mononuclear cells (PBMC) in order to assess the
      cellular origin of these cytokines in patients with therapy resistant epilepsy.
      METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10
      patients with therapy resistant localization-related epilepsy and in healthy
      volunteers. The spontaneous and exogenously stimulated production of these
      cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific
      cytokine production was studied using flow cytometry. RESULTS: Highly pro
      inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta
      ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS
      stimulated cytokine release was similar in PBMC cultures of patients and control
      subjects. When cells were stimulated with OKT3 the cytokine response profiles in
      patients with epilepsy were almost opposite (anti-inflammatory) to the profile
      which was observed in circulating blood. Low IL-6 was observed in cell cultures
      of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed
      that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar
      in patients and control subjects. CONCLUSIONS: Patients with therapy resistant
      epilepsy display a pro-inflammatory profile of plasma cytokines without any
      evidence of increased production from PBMC. These results suggest that the most
      likely origin for these cytokines is the brain, where cytokines can exert
      neuromodulatory functions.

PMID- 15246123
TI  - Genetic programming outperformed multivariable logistic regression in diagnosing
      pulmonary embolism.
AB  - OBJECTIVE: Genetic programming is a search method that can be used to solve
      complex associations between large numbers of variables. It has been used, for
      example, for myoelectrical signal recognition, but its value for medical
      prediction as in diagnostic and prognostic settings, has not been documented.
      STUDY DESIGN AND SETTING: We compared genetic programming and the commonly used
      logistic regression technique in the development of a prediction model using
      empirical data from a study on diagnosis of pulmonary embolism. Using part (67%)
      of the data, we developed and internally validated (using bootstrapping
      techniques) a diagnostic prediction model by genetic programming and by logistic
      regression, and compared both on their predictive ability in the remaining data
      (validation set). RESULTS: In the validation set, the area under the ROC curve of
      the genetic programming model was significantly larger (0.73; 95%CI: 0.64-0.82)
      than that of the logistic regression model (0.68; 0.59-0.77). The calibration of
      both models was similar, indicating a similar amount of overoptimism. CONCLUSION:
      Although the interpretation of a genetic programming model is less intuitive and
      this is the first empirical study quantifying its value for medical prediction,
      genetic programming seems a promising technique to develop prediction rules for
      diagnostic and prognostic purposes.

PMID- 15246124
TI  - Response shift influenced estimates of change in health-related quality of life
      poststroke.
AB  - OBJECTIVE: The interpretability of changes in perceived health status over time
      is threatened if people experience a response shift. This study assessed whether
      the recovery process following stroke altered individuals' perceptions of past
      health status and the impact that change in internal standards (response shift)
      had on ratings over time. We hypothesized that individuals with stroke would
      experience changes in internal standards, not experienced by the control group.
      Two other hypotheses related to objective criterion measures also were tested.
      STUDY DESIGN AND SETTING: Individuals were recruited through a randomized trial
      of acute poststroke care. Health status was evaluated at baseline (within the
      first week poststroke), 6 and 24 weeks later using the EQ VAS. At 6 and 24 weeks,
      subjects were asked to retrospectively re-evaluate their health status for the
      preceding evaluation using the then test technique. RESULTS: The pattern of mean
      scores was indicative of changes in internal standards among individuals with
      stroke but not for the control group. Memory had an impact on estimates of
      response shift. Hypotheses related to the objective criterion measures were not
      supported. CONCLUSION: The results suggest that there was a change in internal
      standards, and that measures of improvement in health status are different based
      on prospective as compared to retrospective ratings. Further understanding of the
      impact of recall on the assessment of response shift using the then test is
      needed to validate the use of this technique.

PMID- 15246125
TI  - Three independent factors predicted adherence in a randomized controlled trial of
      resistance exercise training among prostate cancer survivors.
AB  - OBJECTIVE: To examine predictors of adherence in a randomized controlled trial of
      resistance exercise training (RET) in prostate cancer survivors receiving
      androgen deprivation therapy. STUDY DESIGN AND SETTING: A randomized controlled
      trial conducted at fitness centers in Ottawa and Edmonton, Canada. Prostate
      cancer survivors (n=155) completed measures of social cognitive variables,
      quality of life (QOL), behavior, and fitness before being randomized to either an
      exercise (n=82) or control (n=73) group. The exercise group was asked to perform
      supervised RET three times per week for 12 weeks. RESULTS: The exercise group
      attended 28.2 of the 36 (78.3%) RET sessions. Univariate analyses revealed eight
      different significant (Ps <.05) predictors of exercise adherence including
      exercise stage of change, intention, age, QOL, fatigue, subjective norm, leg
      press test, and perceived behavioral control. A multivariate analysis indicated
      that there were three independent predictors of adherence that explained 20.4% of
      the variance: exercise stage of change (beta=0.26; P=.013), age (beta=-0.22;
      P=.037), and intention (beta=0.19; P=.073). CONCLUSION: Exercise adherence in the
      trial was very good but not optimal. Adherence was predicted by variables from
      many different categories including social cognitive, QOL, behavioral, fitness,
      and demographic. These findings may have important implications for maximizing
      adherence during clinical trials of exercise in prostate cancer survivors.

PMID- 15246126
TI  - Risk factors of gastroesophageal reflux disease: methodology and first
      epidemiological results of the ProGERD study.
AB  - OBJECTIVE: We describe the design and report the first results of the Progression
      of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest
      prospective study of GERD patients. STUDY DESIGN AND SETTING: Patients were
      recruited at 1,253 centers in Germany, Austria, and Switzerland. Following an
      assessment of medical history, all patients were endoscoped and received
      esomeprazole for 2 to 8 weeks before entering the 5-year observational phase.
      RESULTS: A total of 6,215 patients (53% male, age 54+/-14) were included. Of
      these patients, 46% reported at least daily symptoms, 15% were unable to work at
      least once during the prior year, and 71% had visited a physician due to reflux
      symptoms. Barrett's esophagus (BE) was found in 11% of our GERD patients. In
      polychotomous regression analysis, the main factors related to the occurrence of
      the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender,
      duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors
      associated with longer disease duration were increasing age, male gender, BMI,
      increasing symptom severity, presence of erosive GERD or BE, positive family
      history, and smoking. CONCLUSION: The findings indicate that GERD is a great
      burden for patients, and has significant socioeconomic implications. The long
      term follow-up period with further endoscopic and histologic evaluations, will
      help further our understanding of the natural course of the disease.

PMID- 15246127
TI  - Two prospective studies found that elevated 2-hr glucose predicted male mortality
      independent of fasting glucose and HbA1c.
AB  - OBJECTIVE: To quantify the relative contribution of elevated 2-hr glucose,
      fasting glucose (FPG), and HbA1c to all-cause mortality. STUDY DESIGN AND
      SETTING: A joint analysis of two prospective studies with baseline glycemia
      measurements. RESULTS: The multivariate adjusted hazard ratios (HRs)
      corresponding to a one standard deviation increase in HbA1c were 1.14 (95% CI
      1.03-1.25), 1.08 (0.98-1.19) for FPG and 1.15 (1.05-1.27) for 2-hr glucose,
      respectively. Entering the 2-hr glucose to the model based on the FPG and HbA1c
      significantly improved the prediction of mortality, whereas neither FPG, nor
      HbA1c added significant information once 2-hr glucose was in the models. In
      subjects with FPG <7.0 mmol/L and HbA1c < or = 6.5%, the HR was 1.35 (1.03-1.78)
      in men with 2-hr glucose > or = 7.8 mmol/L compared with men with 2-hr glucose
      <7.8 mmol/L. CONCLUSION: Elevated 2-hr glucose was a predictor of mortality
      independent of the levels of fasting glucose and HbA1c.

PMID- 15246128
TI  - In lung cancer patients, age, race-ethnicity, gender and smoking predict adverse
      comorbidity, which in turn predicts treatment and survival.
AB  - OBJECTIVE: This study evaluates the relationship between
      sociodemographic/exposure factors and comorbidity, and their impact on lung
      cancer treatment and survival. STUDY AND DESIGN SETTING: Data for 1,155 patients
      were abstracted from the Josephine Ford Cancer Center Tumor Registry and medical
      records. Associations were analyzed by linear, logistic, and Cox regression.
      RESULTS: Approximately 88% of patients had > or = 1 of 56 comorbidities assessed.
      In multivariate analysis, comorbidity count was associated with older age, pack
      years smoked, heavy alcohol use, lower socioeconomic status (SES), and female
      gender. Approximately 63% of patients had > or = 1 of 18 adverse prognostic
      comorbidities (AC), and significant independent predictors of AC were age, pack
      years, African-American race/ethnicity, and gender. In multivariate analysis,
      comorbidity count and AC predicted nonreceipt of surgery in localized disease
      (OR(> or = 1 vs. 0 AC)=0.38, 95% 0.18, 0.81) and chemotherapy in advanced disease
      (OR > or = 1 vs. 0 AC)=0.72, 95% 0.51, 1.00). In adjusted analysis, comorbidity
      predicted survival in localized (hazard ratio (HR)(> or = 2 vs. 0 AC)=2.99, 95%
      CI 1.75, 5.10) and advanced lung cancer (HR(> or = 2 vs. 0 AC)=1.56, 95% CI 1.25,
      1.94). CONCLUSION: Comorbidity has important deleterious effects on lung cancer
      outcomes and significant predictors of comorbidity included age, smoking,
      race/ethnicity, SES, alcohol, and gender.

PMID- 15246129
TI  - A randomized trial of interactive group sessions achieved greater improvements in
      nutrition and physical activity at a tiny increase in cost.
AB  - OBJECTIVE: Weight gain may follow altered eating habits and decreased physical
      activity in couples beginning to live together. Mutual support and willingness to
      accept changes in lifestyle at this stage may facilitate positive responses to
      health promotion. We aimed to compare the effects of a diet and physical activity
      program in couples using a randomized controlled trial. STUDY DESIGN AND SETTING:
      Couples were randomized to a control group or to one of two intervention groups
      in whom the program was either delivered mainly by mail or with a combination of
      mail-outs and interactive group sessions. RESULTS: Diets, physical fitness, and
      blood cholesterol improved up to 12 months after beginning the 4-month program,
      mainly in the interactive group. In that group, at the end of the program, the
      estimated cost was 445.30 dollars (111.33 dollars/month) per participant per unit
      change in outcome variables, only 0.03 dollars per participant per month more
      than the group receiving the program mainly by mail. One year after beginning the
      program, costs per participant per month were 38.37 dollars in the interactive
      group and 38.22 dollars in the group receiving the program mainly by mail-out.
      CONCLUSION: The changes observed in cardiovascular risk factors could translate
      to a substantial cost-savings relating to health.

PMID- 15246130
TI  - Female specialists were more likely to respond to a postal questionnaire about
      drug treatments for Alzheimer disease.
AB  - OBJECTIVE: To assess demographic predictors of response for specialists who were
      mailed a postal questionnaire on drug treatments for Alzheimer disease. STUDY
      DESIGN AND SETTING: The questionnaire was sent to 317 specialists in Quebec,
      Canada. Demographic variables included specialty, urban/rural practice, language,
      sex, and 'number of years since receiving a medical license.' The specialists
      were stratified according to responder status (i.e., respondent/nonrespondent),
      and respondents were further stratified as early or late responders. Variables
      differing between these strata were entered into logistic regression models to
      see if they predicted response. RESULTS: Only 'female sex' was a predictor of
      response in the respondent/nonrespondent analysis (OR 2.03; 95% CI 1.17, 3.53).
      No demographic variables predicted early or late response. CONCLUSION:
      Researchers planning postal questionnaires should target male specialists with
      modified or additional mailings to increase response and reduce the potential for
      nonresponse bias. Caution should be exercised when comparing early vs. late
      responders as a means of assessing nonresponse bias.

PMID- 15246131
TI  - Participants and refusers in a telephone interview about hormone replacement
      therapy were equally likely to be taking it.
AB  - OBJECTIVE: To address a major concern in pharmacoepidemiology studies related to
      whether the characteristics of responders are different from those who refuse to
      participate. STUDY DESIGN AND SETTING: We compared utilization of postmenopausal
      hormone replacement therapy (HRT) in women who agreed to participate in a
      telephone interview on HRT utilization and in women who refused to participate in
      the telephone interview. Information on HRT utilization among responders and
      refusers was independently available to us from a claims database (the Healthcare
      Management Alternatives, HMA, in Philadelphia), showing drugs dispensed to these
      patients. RESULTS: Out of a random sample of 213 women selected from the claims
      database whom we contacted, 154 (72.3%) women agreed to participate and 59
      (32.7%) women refused. Among the 154 women who agreed to participate, 79 (51.3%,
      95% CI: 43.1-59.4%) were shown by the database to have been dispensed an HRT
      during the 15-month period January 1995 through March 1996. Among the 59 women
      who refused to participate, 30 (50.8%, 95% CI: 37.5-64.1%) were shown by the
      database to have been dispensed an HRT during the same period. CONCLUSION: Thus,
      we have evidence that use of HRT was almost identical in responders and
      nonresponders.

PMID- 15246132
TI  - The prevalence of contact allergy differed between population-based and clinic
      based data.
AB  - OBJECTIVE: Epidemiologic evidence on contact allergy (CA) largely relies on
      clinical studies. However, the effects of the selection process until
      consultation as patient are largely unclear. STUDY DESIGN AND SETTING:
      Prevalences of contact allergy to important allergens estimated from the
      population-based nested case-control study "KORA Allergy Study" in Augsburg,
      Germany (a subsample from the third MONICA survey in 1997/1998, n=1141), were
      compared with proportions found in the Department of Dermatology of the Augsburg
      Municipal Hospital in patients of similar age patch tested between 1997 and 2000
      (n=555). Prevalences were standardized for sex, age, and atopic dermatitis as
      potential confounders. RESULTS: Among the 25 substances tested, the fragrance mix
      (MONICA, estimated from the KORA Allergy Study: 11.4%, hospital: 12.9%) and
      nickel (MONICA: 9.9%, hospital: 12.9%) were the most common allergens. Larger
      differences between prevalences were noted particularly with ingredients of
      topicals used to treat varicose ulcers-a speciality of the Augsburg department,
      which is also reflected by comparing the department with the whole Information
      Network of (n =40) Departments of Dermatology (IVDK). CONCLUSION: This locally
      matched comparison illustrates the differential effect of selection until
      presentation in dermatological departments.

PMID- 15246133
TI  - Measles incidence estimations based on the notification by general practitioners
      were suboptimal.
AB  - OBJECTIVE: The aim of this study was to determine the notification by general
      practitioners (GPs) to the Municipal Health Service (MHS) and the presentation of
      measles complaints by patients to the GP during a measles epidemic in a 78%
      vaccinated population. STUDY DESIGN AND SETTING: Measles cases in children under
      13 years were identified via questionnaires, GPs' records, and MHS's records.
      Consultation rate, notification rate, and completeness of notification were
      determined. Determinants of consultation were identified by multivariable
      logistic regression analysis. RESULTS: Among 1654 responders, 164 measles cases
      were identified. Consultation rate: 30%; notification rate: 30% (range among GPs:
      0-62%); completeness of notification: 9%. Determinants of GP consultation:
      perceived seriousness of illness (adjusted OR 45; 95% CI: 6-347), self-reported
      complications (adjusted OR 9; 95% CI: 1-70), and need to consult for respiratory
      tract infections (adjusted OR 8; 95% CI: 1-51). CONCLUSION: Incidence estimations
      based on the notification by GPs to the MHS are suboptimal for measles in The
      Netherlands. Perceived seriousness of illness seemed to be the most important
      factor to consult.

PMID- 15246134
TI  - Case-fatality rates for myocardial infarction declined in Denmark and Sweden
      during 1987-1999.
AB  - OBJECTIVE: To evaluate trends in prognosis after acute myocardial infarction
      (AMI) between Denmark and Sweden using routinely collected data and different
      case-fatality measures. STUDY DESIGN AND SETTING: We compared three case-fatality
      measures during 1987-1999 using national registries in Denmark and Sweden, and
      extended these measures with underlying deaths of ischemic heart disease and
      sudden deaths of unknown cause. RESULTS: Changed coding practice distorted trends
      of case fatality rates during the day of the event. In general, Denmark had
      higher case-fatality rates, but trends in hospital-based rates were very similar,
      except for men 35-64 years old; Denmark declined more steeply. Short- and long
      term prognosis improved considerably: the odds ratios for case fatality during
      days 1-28 for 1999 vs. 1987 were 0.48 among men in Denmark (women 0.58) and 0.53
      among men in Sweden (women 0.55) and the odds ratios for case fatality during
      days 29-365 for 1999 vs. 1987 were 0.56 among men in Denmark (women 0.65) and
      0.66 among men in Sweden (women 0.67). CONCLUSION: Short- and long-term prognosis
      improved considerably during 1987-1999 in Denmark and Sweden. Case fatality
      during the day of the event is epidemiologically important, but less certain than
      case-fatality measures defined after the day of the event when comparing
      countries.

PMID- 15246135
TI  - A new approach in the determination of the minimal clinically meaningful
      difference.

PMID- 15246137
TI  - National Health and Nutrition Examination Survey 1999-2000: effect of observer
      training and protocol standardization on reducing blood pressure measurement
      error.

PMID- 15246139
TI  - Radiographic assessment of the hindfoot and ankle.
AB  - This article is an introduction to a complex topic on radiographic views as they
      relate to alignment of the ankle and hindfoot to the lower leg. Patient
      positioning as it relates to obtaining full-length lower extremity radiograph
      views are discussed along with contralateral radiographs, which are useful and
      important for comparative purposes.

PMID- 15246140
TI  - Deformity correction planning for hindfoot, ankle, and lower limb.
AB  - Many patients with foot and ankle deformities have concurrent deformities
      (osseous and soft tissue), with or without limb length discrepancies. Lower
      extremity deformities and limb length discrepancies typically result from trauma,
      congenital abnormality, avascular necrosis, previous surgery, nonunion, and
      malunion. Limb deformity correction requires extensive surgical experience
      because many considerations and factors apply to realignment. The considerations
      and factors regarding realignment are highlighted throughout this article.

PMID- 15246141
TI  - Application of bone grafts in podiatric surgery.
AB  - The application of bone grafting was first reported in the late 1600s, but has
      only recently become widely used in podiatric surgery. This increase can be
      accredited to many sources, such as the recent surge in literature advocating its
      use and the advances in allograft technology that have made it more readily
      available. There are many new types of allograft bone implants evolving each year
      with better osteogenic potential and structural rigidity.

PMID- 15246142
TI  - Management of osteomyelitis.
AB  - Osteomyelitis is an infection of the medullary or cortical bone that is becoming
      more difficult to cure with the increasing prevalence of methicillin- and
      vancomycin-resistant organisms. This article discusses the etiology of
      osteomyelitis and the effectiveness of various treatment options.

PMID- 15246143
TI  - Corrective ankle osteotomies.
AB  - Corrective ankle osteotomies are periarticular osteotomies of the fibula, distal
      tibial metaphysis, or distal tibial metaphyseal diaphyseal junction. These
      osteotomies are indicated when angular, rotational, or translational malalignment
      is present. The author presents a review of the literature and in-depth surgical
      technique for each procedure, as well as a review of how to prevent and address
      the most common complications encountered.

PMID- 15246144
TI  - Repair of malunions after ankle arthrodesis.
AB  - Ankle arthrodesis is an operation that produces fusion of the talocrural joint.
      Ideally, the ankle is fused in a position of slight valgus, neutral dorsiflexion,
      midsagittal translation, slight posterior translation, symmetric external
      rotation, and plantigrade foot alignment. Malunion after ankle arthrodesis is
      characterized as a deviation from this ideal position. The derangement may
      produce inefficient or painful gait and pain or dysfunction at the hip, knee, or
      foot. Preoperative planning is essential to achieve a final plantigrade foot
      position. Correction is accomplished through the ankle arthrodesis itself, the
      foot, or the supramalleolar tibia. Complications of ankle malunion repair include
      nonunion; malunion; nerve, vessel or tendon injury; and infection.

PMID- 15246145
TI  - Revision of malunited ankle fractures.
AB  - Malunion of an ankle fracture can lead to considerable pain and loss of function.
      Restoration of the normal anatomical alignments can restore function and minimize
      the onset of degeneration that will lead to severe arthrosis requiring an
      arthrodesis. This article outlines common causes of ankle malunion and treatment
      options.

PMID- 15246146
TI  - Total ankle arthroplasty: a review of 11 current ankle implants.
AB  - Introduced in the early 1970s, total ankle arthroplasty offered patients with
      debilitating ankle arthritis reduction in pain and almost normal mobility at the
      ankle joint. The idea of replacing an arthritic ankle joint with a mobile ankle
      prosthesis was originally welcomed to replace ankle arthrodesis. Unfortunately,
      high failure rates of first-generation implants led many surgeons in the United
      States to recommend ankle arthrodesis as the best alternative. An improved
      understanding of ankle joint mechanics, implant material and design, and surgical
      technique has led to the development of several second-generation implants that
      are being used successfully throughout the world. As short-term, mid-term, and
      long-term results continue to be published, there has been a momentous change in
      the outlook of total ankle arthroplasty as a viable option to ankle arthrodesis.

PMID- 15246147
TI  - Revision of malaligned triple arthrodesis: a case report.
AB  - Malalignment of a triple arthrodesis can pose significant challenges to the foot
      and ankle surgeon. Lack of a plantigrade foot will not be well tolerated by the
      patient and will often require revision of the original surgery. This article
      presents a review of the treatment algorithm used to address this unique problem.
      A case study based on this approach is also presented.

PMID- 15246148
TI  - Treatment of nonunited hindfoot fusions.
AB  - The management of delayed union and nonunion is complex and is contingent on
      appropriate diagnosis and classification. Detection techniques and treatment
      options, including cast immobilization, electrical stimulation, surgical repair,
      or a combination of regimens, are discussed in this article.

PMID- 15246149
TI  - Extracorporeal shockwave therapy for plantar fasciitis and other musculoskeletal
      conditions utilizing the Ossatron--an update.
AB  - Extracorporeal shockwave therapy for treatment of plantar fasciitis and other
      areas of the body has been well documented since the early 1990s. A high level of
      efficacy and patient satisfaction after undergoing electrohydraulic shock wave
      treatments has been reported not only for plantar fasciopathy but other
      musculoskeletal indications. Electrohydraulic devices have a bimodal response:
      early suppression of nocioceptor reactivity followed by subsequent target tissue
      remodeling and healing through neovascularization and recruitment of new tissue
      target specific cells. Both responses are not present with low energy
      electromagnetic devices. The focus of this article is treatment of chronic
      proximal plantar fasciitis; however, other pathologies of the lower extremity
      demonstrate great promise for this emerging technology.

PMID- 15246150
TI  - Subtalar joint instability: current clinical concepts.
AB  - There has been extensive research and investigation into the subtalar joint
      (STJ), yet the biomechanics that relate to its anatomic function, especially
      instability after injury, are surrounded by controversy. With a mechanism of
      injury closely related to the classic inversion ankle sprain, chronic instability
      can result following trauma to the lateral ligamentous support network of either
      joint. Over the past decades there have been countless examples in the literature
      challenging the current standard of evaluation and treatment of the "subtalar
      sprain." New technologies have offered varied approaches to diagnostic
      capability, each with its own strengths and weaknesses, ranging from standard
      radiographs to CT and MRI. A review of the literature should aid in deciphering
      the controversy surrounding this aspect of podiatric medicine.

PMID- 15246151
TI  - Pantalar arthrodesis.
AB  - Pantalar arthrodesis is a demanding procedure that serves a useful purpose for
      stabilization of the ankle, rearfoot, and midfoot. These fusions should be
      recognized as salvage procedures in the treatment of unstable and debilitating
      conditions as a result of severe degenerative joint disease, rheumatoid
      arthritis, neuropathic joint destruction, and paralytic or flail extremity
      dysfunction. As with all salvage-type procedures, patient and physician
      expectations must be the same to afford an acceptable and functional
      postoperative result.

PMID- 15246155
TI  - Allogeneic hematopoietic stem cell transplantation with a reduced-intensity
      conditioning regimen for treatment of metastatic renal cell carcinoma: single
      institution experience with a minimum 1-year follow-up.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of
      allogeneic hematopoietic stem cell transplantation with a reduced-intensity
      conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell
      carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National
      Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA
      identical relative was identified for 12 patients. Nine patients underwent RIST.
      The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66
      mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs
      host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients
      achieved engraftment without grade III to IV nonhematologic regimen-related
      toxicity. All patients achieved complete donor-type chimerism without donor
      lymphocyte infusion by day 60. Four patients developed acute GVHD, and four
      developed chronic GVHD. One patient (11%) achieved partial response. As of July
      2003, six patients were alive at median follow-up of 681 days. The actuarial
      overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival
      rate tended to be higher in the 12 patients with a matched donor than in the
      other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST
      procedure is feasible without severe toxicity. The efficacy of RIST for RCC
      should be confirmed in phase II/III clinical trials.

PMID- 15246156
TI  - Erythroblasts derived in vitro from embryonic stem cells in the presence of
      erythropoietin do not express the TER-119 antigen.
AB  - OBJECTIVE: In this study, we analyzed murine primitive erythropoiesis by
      coculturing Flk-1+ ES-derived cells with OP9 to find efficient culture conditions
      for erythroid cell induction. We utilized a nonserum culture system and EPO
      (erythropoietin) and found that this cytokine had unique properties. MATERIALS
      AND METHODS: ES cells (E14.1) were first differentiated to Flk-1+ cells and then
      cocultured with OP9 stromal cells. BIT9500 was used as a serum replacement. The
      erythroid morphology, hemoglobin types, and TER-119 expression levels were
      analyzed. RESULTS: Primitive erythroid cells with embryonic hemoglobin were
      generated very efficiently when the serum-containing culture was converted to the
      nonserum system. In this serum-free culture, TER-119+ erythroblasts appeared
      first on day 2 and maturation proceeded until day 7. When EPO was added to this
      coculture, the number of induced floating cells increased twofold to threefold.
      Unexpectedly, the erythroid-specific antigen TER-119 expression of these cells
      was drastically reduced. Since reduced TER-119 expression is usually interpreted
      as maturation arrest, we examined the phenotypic features of the EPO-treated
      cells. We found, however, no evidence of maturation arrest in the aspects of
      morphology and hemoglobin content. EPO did not suppress TER-119 expression of
      erythroblasts derived from fetal liver or adult bone marrow. CONCLUSIONS: Our
      results showed that EPO had the unusual property of inducing TER-119-
      erythroblasts in ES-derived primitive erythropoiesis. It is likely that this
      effect is unique to primitive erythropoiesis.

PMID- 15246154
TI  - In search of "stemness".
AB  - Stem cells have been identified and characterized in a variety of tissues. In
      this review we examine possible shared properties of stem cells. We suggest that
      irrespective of their lineal origin, stem cells have to respond in similar ways
      to regulate self-renewal and differentiation and it is likely that cell-cycle
      control, asymmetry/differentiation controls, cellular protective and DNA repair
      mechanisms, and associated apoptosis/senescence signaling pathways all might be
      expected to be more highly regulated in stem cells, likely by similar mechanisms.
      We review the literature to suggest a set of candidate stemness genes that may
      serve as universal stem cell markers. While we predict many similarities, we also
      predict that differences will exist between stem cell populations and that when
      transdifferentiation is considered genes expected to be both similar and
      different need to be examined.

PMID- 15246157
TI  - A Wilms tumor cell line, HFWT, can greatly stimulate proliferation of CD56+ human
      natural killer cells and their novel precursors in blood mononuclear cells.
AB  - OBJECTIVE: A Wilms tumor cell line, HFWT, selectively stimulates expansion of
      natural killer (NK) cells from human peripheral blood mononuclear cells (PBMC).
      In this study, we attempted to identify NK precursors in PBMC or in cord blood
      mononuclear cells (CBMC) that preferentially respond to feeder HFWT cells.
      MATERIALS AND METHODS: Human NK cells or candidate precursor cells were
      fractionated from PBMC or CBMC by magnetic antibody cell sorting or by flow
      cytometry and applied to limiting dilution analysis to determine the proportion
      of NK/NK precursor cells, which are able to proliferate on irradiated HFWT cells.
      NK and NK precursor cells were cultured in medium containing interleukin-2 (IL
      2). Expansion of NK cells from both resting NK cells and NK precursor cells was
      examined using proliferation from single cells, expression of NK cell markers,
      and cytotoxic activity. RESULTS: In the limiting dilution analysis, NK cells
      expanded on irradiated HFWT cells not only from CD3-CD56bright and CD3-CD56dim NK
      cells, but also from CD16+/-CD122+ cells in the lineage-negative (Lin-, CD3-CD14
      CD19-CD56-) cell fraction. The feeder HFWT cells stimulated Lin-CD122+ cell
      proliferation more strongly than feeder cells from the well-known human NK target
      cell line K562. CBMC contained significantly higher percentages of Lin-CD122+
      cells than PBMC. CONCLUSION: CD3-CD14-CD19-CD56- cells expressing CD122+ (a
      subunit of the IL-2 receptor) preferentially respond to HFWT feeder cells and are
      novel precursors of CD3-CD56+ NK cells in human PBMC and CBMC.

PMID- 15246158
TI  - CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive
      phenotype and specific expression of forkhead box p3 (Foxp3) gene.
AB  - OBJECTIVE: To address the role of cord blood (CB) CD25+CD4+ T cells, the gene
      expressions and function of this subset were analyzed. MATERIALS AND METHODS:
      CD25+CD4+ T cells fractionated from CB of term and preterm infants were subjected
      to flow cytometry, quantitative polymerase chain reaction analysis for cytokines,
      costimulatory molecules, and transcription factors, and functional assays.
      RESULTS: Human preterm CB contained a high proportion of CD25+CD4+ T cells that
      declined with gestational age to the level of adult peripheral blood (PB). CD25+
      or CD25-CD4+ T cells in CB had a higher frequency of CD45RA+ and CD38+ cells than
      in PB. CB CD25+CD4+ T cells less frequently expressed CD45RO, CD71, and HLA-DR
      than PB CD25+CD4+ T cells, despite similar expressions on CB and PB CD25-CD4+ T
      cells. No expression of IL-10, transforming growth factor-beta, interleukin-4,
      and interferon-gamma mRNA differed between CB CD25+CD4+ and CD25-CD4+ T cells, in
      contrast to the high interleukin-10 expression in PB CD25+CD4+ T cells. CTLA-4
      was more transcribed in CB and PB CD25+CD4+ T cells than in the counterpart CD25
      CD4+ T cells. CD28 or ICOS was similarly expressed in CB and PB T cells. CB
      CD25+CD4+ T cells effectively suppressed the proliferation of CB CD25-CD4+ T
      cells in a dose-dependent manner. Human CB and PB CD25+CD4+ T cells
      preferentially transcribed Foxp3, which governs the regulatory function of this
      subset in mice. CONCLUSIONS: These results suggest that CB contains CD25+CD4+
      regulatory T cells as a functionally mature population with naive phenotype. This
      subset may naturally arise and decline in fetus to play a potential
      immunoregulatory role in intrauterine life.

PMID- 15246159
TI  - Effect of KRN7000 on induced graft-vs-host disease.
AB  - OBJECTIVE: Graft-vs-host disease (GVHD) is a serious complication of allogeneic
      stem cell transplantation (SCT) and donor lymphocyte infusion (DLI), for which no
      effective therapy exists. In our study, KRN7000, a synthetic analog of alpha
      galactosylceramide, known for its ability to activate natural killer T cells, was
      tested for its ability to prevent onset of GVHD in a murine model of
      haploidentical major histocompatible (MHC) mismatched hematopoietic cells.
      METHODS: Irradiated (BALB/cXC57BL/6)F1 mice were inoculated with parental C57BL/6
      splenocytes with or without SCT. KRN7000 was given intraperitoneally as single or
      multiple doses at 100 microg/kg/dose and mice were followed up for GVHD clinical
      symptoms and for survival. The effect of KRN7000 treatment was also tested in
      vitro for the induction of suppression of alloreactivity in mixed lymphocyte
      reaction (MLR). RESULTS: KRN7000 prevented development of GVHD symptoms in almost
      all mice and 52/53 mice maintained a healthy profile for more than 235 days. Most
      vehicle-treated mice or untreated controls died of GVHD within a median of 3
      weeks. KRN7000 treatment did not prevent engraftment of donor cells following
      sublethal total-body irradiation (TBI) and allowed durable persistence of donor
      cells following lethal TBI and SCT. Splenocytes derived from KRN7000-treated mice
      suppressed efficiently mixed lymphocyte reaction (MLR) in vitro. CONCLUSION: GVHD
      induced by alloreactive lymphocytes can be prevented by KRN7000. GVHD prevention
      may be accomplished by regulation of T cell function and might thus provide a new
      modality for safer SCT and DLI.

PMID- 15246160
TI  - Gene expression profile of primary human CD34+CD38lo cells differentiating along
      the megakaryocyte lineage.
AB  - OBJECTIVE: To identify genes involved in megakaryopoiesis, high-density
      oligonucleotide microarrays were used to compare transcript profiles from
      undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes (MKs).
      MATERIALS AND METHODS: Megakaryocyte differentiation was achieved in vitro by
      inducing primary human CD34+CD38lo cells in serum-deprived media supplemented
      with the cytokine combination of interleukin-3, interleukin-6, stem cell factor,
      and thrombopoietin for 10 days. Three replicate microarray experiments were
      performed using hematopoietic cells isolated from three different organ donors
      and high-density oligonucleotide microarrays. RESULTS: Analysis of gene array
      data resulted in 304 differentially expressed genes (p < or = 0.001, fold change
      > or = 3). A third of the 25 most highly up-regulated genes were known to
      participate in hemostasis (z = 6.75), and no genes known to be associated with
      MKs were among the down-regulated genes. We also found a large proportion of up
      regulated transcripts in gene ontology categories of adhesion and receptor
      activity (85%) and signal transduction activity (68%). At the same time, 70% of
      genes within transcription factor functions were down-regulated. Confirmatory
      studies indicated that the array results correlated with mRNA and protein
      expression levels in primary MKs. CONCLUSION: This study provides a global
      expression profile of human MKs and a list of novel and previously
      uncharacterized candidate genes that are important components of
      megakaryopoiesis.

PMID- 15246161
TI  - Prostate apoptosis response gene-4 (par-4) abrogates the survival function of
      p185(BCR-ABL) in hematopoietic cells.
AB  - OBJECTIVE: Prostate apoptosis response gene-4 (par-4) is deregulated in acute and
      chronic lymphatic leukemia. Given its pro-apoptotic role in neoplastic
      lymphocytes and evidence that par-4 antagonizes oncogenic Ras in solid tumors, we
      hypothesized that par-4 may act as a tumor suppressor impairing transformation
      induced by p185(BCR-ABL). MATERIALS AND METHODS: The capacity of par-4 to
      interfere with factor independence induced by p185(BCR-ABL) and V12ras was
      evaluated by analysis of factor-independent growth of p185(BCR-ABL)/ par-4 and
      V12ras/par-4 transduced cells. The expression of par-4 and p185(BCR-ABL) by the
      respective constructs was controlled by Western blot analysis. Activated Ras was
      detected by pull-down assay in the cell clones expressing p185(BCR-ABL) in the
      absence and presence of par-4. RESULTS: Expression of p185(BCR-ABL) causes factor
      independence, signifying a conversion toward a transformed phenotype in
      hematopoietic precursors. We demonstrate that par-4 completely abolishes factor
      independence induced by p185(BCR-ABL) and partially abrogates factor independence
      caused by activated V12ras. Evaluating the underlying molecular mechanisms, we
      show that par-4 hinders activation of oncogenic Ras and causes concomitant
      disruptions of p185(BCR-ABL)-mediated signaling. CONCLUSION: We provide the first
      evidence that par-4 exhibits an antitransforming capacity by antagonizing
      p185(BCR-ABL)-induced factor-independent proliferation in hematopoietic cells.

PMID- 15246162
TI  - Human placenta-derived mesenchymal progenitor cells support culture expansion of
      long-term culture-initiating cells from cord blood CD34+ cells.
AB  - OBJECTIVE: Allogeneic transplantation with umbilical cord blood (UCB) in adult
      recipients is limited mainly by a low CD34+ cell dose. To overcome this
      shortcoming, human placenta as a novel source of human mesenchymal progenitor
      cell (MPC) was incorporated in an attempt to expand CD34+ cells from UCB in
      vitro. MATERIALS AND METHODS: Human placenta MPC was isolated and characterized
      by morphologic, immunophenotypical, and functional analysis. UCB CD34+ cells were
      expanded by coculture with placental MPC. Suitable aliquots of cells were used to
      monitor cell production, clonogenic activity, and long-term culture-initiating
      culture (LTC-IC) output. Finally, the immunoregulatory effect of placental MPC
      was evaluated by T-cell proliferation assay. RESULTS: In its undifferentiated
      state, placental MPC displayed fibroblastoid morphology; was CD73, CD105, CD29,
      CD44, HLA-ABC, and CD166 positive; produced fibronectin, laminin, and vimentin;
      but was negative for CD14, CD31, CD34, CD45, HLA-DR, and alpha-smooth muscle
      actin. Functionally, it could be induced into adipocytes, osteocytes, and
      chondrocytes. In vitro expansion of UCB hematopoietic cells, when cocultured with
      placental MPC in the presence of cytokines, was significantly enhanced: CD34+
      cells by 14.89 +/- 2.32 fold; colony-forming cell (CFC) by 36.73 +/- 5.79 fold;
      and LTC-IC by 7.43 +/- 2.66 fold. Moreover, placental MPC could suppress T-cell
      proliferation induced by cellular stimuli. CONCLUSION: These results strongly
      suggest that human placental MPC may be a suitable feeder layer for expansion of
      hematopoietic progenitors from UCB in vitro.

PMID- 15246163
TI  - Quiescent (5-fluorouracil-resistant) aplastic anemia hematopoietic cells in
      vitro.
AB  - OBJECTIVE: Bone marrow from aplastic anemia (AA) patients shows reduced numbers
      in long-term culture (LTC)-initiating cell (LTC-IC) assays. The LTC-IC assay is
      based on assumptions of the culture kinetics of normal hematopoietic stem cells
      (HSC), which are not necessarily justified in a disease state. We therefore
      undertook a detailed examination of the kinetics of quiescent HSC from AA
      patients in LTC. METHODS: Colony formation by quiescent HSC in LTC was tested by
      pretreating control (n=6) and AA bone marrow (n=7) with 5-fluorouracil. Secondly,
      we manipulated normal samples to inoculate cultures with proportions of CD34+
      cells similar to those from AA samples. We obtained enough CD34+ cells to
      reconstitute one AA sample to "normal" levels. RESULTS: Patient cells showed
      altered kinetics with rapid proliferation and premature termination of LTC. In
      vivo, decreased numbers of HSC may induce rapid proliferation and
      differentiation; a similar phenomenon could explain the observations in culture.
      We therefore manipulated normal samples to contain a proportion of CD34+ HSC
      similar to that in AA samples. Although absolute numbers of secondary colonies in
      LTC were reduced, the kinetics of culture were not altered. However, when AA
      CD34+ HSC were reconstituted to "normal" levels, the cultures still demonstrated
      early termination. CONCLUSIONS: The kinetics of LTC are not affected by CD34+ HSC
      number. However, quiescent HSC derived from patients with AA have qualitative
      differences from normal cells, as reflected by distinct kinetics in long-term
      culture. This has implications for the interpretation of the LTC-IC assay with AA
      samples.

PMID- 15246164
TI  - Erythroid-like cells from neural stem cells injected into blastocysts.
AB  - OBJECTIVE: In contrast to embryonic stem (ES) cells, which are able to give rise
      to all cell types of the body, somatic stem cells have been thought to be more
      limited in their differentiation potential in that they are committed to generate
      only cells of their tissue of origin. Unexpectedly, some recent data suggest that
      somatic stem cells isolated from one tissue can also generate cells of
      heterologous tissues and organs, implying that somatic stem cells have a greater
      potential for differentiation. METHODS: To explore further the developmental
      potential of murine neural stem cells (NSCs) we injected cultured NSCs as
      neurospheres into preimplantation blastocysts and determined the seeding by donor
      cells in tissues of developing chimeric fetal and adult animals. RESULTS: We
      frequently detected progeny of injected NSCs both in embryos and in adult
      animals. In embryos we observed transient seeding of donor cells to hematopoietic
      tissues and generation of NSC-derived cells that express globin genes and an
      erythroid-specific cell-surface marker. In adults progeny of NSCs were mostly
      detected in neural tissues. The observed low level of chimerism of wild-type NSCs
      was increased if we injected stem cells expressing a bcl-2 transgene, without
      changing the seeding pattern. CONCLUSION: These results suggest that cultured
      NSCs, following their injection into blastocysts, generate at mid-gestation
      erythroid-like cells but later, in adult chimeric mice, engraftment mainly
      persisted in neural tissues.

PMID- 15246165
TI  - Social inequality and depressive disorders in Bahia, Brazil: interactions of
      gender, ethnicity, and social class.
AB  - We conducted a study of the association between gender, race/ethnicity, and
      social class and prevalence of depressive disorders in an urban sample (N = 2302)
      in Bahia, Brazil. Individual mental health status was assessed by the PSAD/QMPA
      scale. Family SES and head of household's schooling and occupation were taken as
      components for a 4-level social class scale. Race/ethnicity (white, moreno,
      mulatto, black) was assessed with a combination of self-designation and a system
      of racial classification. The overall 12-month prevalence of depressive symptoms
      was 12%, with a female:male ratio of 2:1. Divorced/widowed persons showed the
      highest prevalence and single the lowest. There was a negative correlation with
      education: the ratio college educated:illiterate was 4:1. This gradient was
      stronger for women than men. There was no F:M difference in depression among
      Whites, upper-middle classes, college-educated, or illiterate. Prevalence ratios
      for single, widowed and Blacks were well above the overall pattern. Regarding
      race/ethnicity, higher prevalences of depression were concentrated in the Moreno
      and Mulatto subgroups. There was a consistent social class and gender
      interaction, along all race/ethnicity strata. Three-way interaction analyses
      found strong gender effect for poor and working-class groups, for all
      race/ethnicity strata but Whites. Black poor yielded the strongest gender effect
      of all (up to nine-fold). We conclude that even in a highly unequal context such
      as Bahia, Blacks, Mulattos and women were protected from depression by placement
      into the local dominant classes; and that the social meaning of ethnic-gender
      generation diversity varies with being unemployed or underemployed, poor or
      miserable, urban or rural, migrant or non-migrant.

PMID- 15246166
TI  - Individualization and inequalities in health: a qualitative study of class
      identity and health.
AB  - It has been argued that social class, if not dead, is at least a 'zombie
      category' in contemporary Western society. However, epidemiological evidence
      shows that class-based inequalities have either persisted or widened, despite
      overall improvements in the health of Western populations. This article presents
      an exploratory qualitative study of the individualization of class identity and
      health conducted in a southern English city. Findings are presented in
      consideration of two competing argumentative positions around which participants
      worked to negotiate class identity and health. The first of these positions
      denied the significance of class for identity and health and was associated with
      the individualised heroic and stoic narratives of working class identity. The
      second position acknowledged the reality of class relations and their
      implications for health and identity, being associated with structurally and
      politically orientated narratives of middle class identity. In sum, resistance to
      class was associated with talk about individual, private experience whereas the
      acceptance of class was linked to discussion of health as a wider social or
      political phenomenon. This evidence lends qualified support to the
      individualization thesis: inequalities in health existing on structural or
      material levels are not simply reproduced, and indeed in some contexts may even
      juxtapose, accounts of social identity in interview and focus group contexts.
      Class identity and health are negotiated in lay talk as participants shift
      argumentatively back and forth between competing positions, and public and
      private realms, in the attempt to make sense of health and illness. The promotion
      of greater awareness and interest in health inequalities within wider public
      discourse may well help support attempts to tackle these injustices.

PMID- 15246167
TI  - Job characteristics as mediators in SES-health relationships.
AB  - We focus on physical and psychosocial job characteristics as mediators in the
      relationship between socioeconomic status (SES) and health. From sociological
      research on the stratification of employment outcomes we expect that people with
      less education, lower earnings, and lower levels of occupational standing have
      more physically and psychosocially demanding jobs. From the occupational stress,
      ergonomics, and job design literatures, we expect that people with more
      physically and psychosocially demanding jobs have less favorable health outcomes.
      Consequently, we expect to find that job characteristics play an important
      mediating role in associations between SES and self-assessed overall health and
      cardiovascular and musculoskeletal health problems. To address these hypotheses,
      we use data from the Wisconsin Longitudinal Study (WLS). We find support for our
      hypotheses, although the extent to which job characteristics mediate SES-health
      relationships varies across health outcomes and by sex.

PMID- 15246168
TI  - Men's influences on women's reproductive health: medical anthropological
      perspectives.
AB  - Reproductive health has emerged as an organizational framework that incorporates
      men into maternal and child health (MCH) programs. For several decades, medical
      anthropologists have conducted reproductive health research that explores male
      partners' effects on women's health and the health of children. This article
      summarizes exemplary research in this area, showing how ethnographic studies by
      medical anthropologists contribute new insights to the growing public health and
      demographic literature on men and reproductive health. The first half of the
      article begins by exploring reproductive rights, examining the concept from an
      anthropological perspective. As part of this discussion, the question of equality
      versus equity is addressed, introducing anthropological perspectives on ways to
      incorporate men fairly into reproductive health programs and policies. The second
      half of the article then turns to a number of salient examples of men's relevance
      in the areas of contraception, abortion, pregnancy and childbirth, infertility,
      and fetal harm. Medical anthropological research--as well as prominent gaps in
      that research--is highlighted. The article concludes with thoughts on future
      areas of anthropological research that may improve understandings of men's
      influences on women's reproductive health.

PMID- 15246169
TI  - The rhetoric of "natural" in natural childbirth: childbearing women's
      perspectives on prolonged pregnancy and induction of labour.
AB  - It is widely known that the notion of prolonged pregnancy, defined medically as
      41+ or 42+ weeks gestation, has been hotly debated within the medical and
      midwifery communities for many decades. Within this debate, pregnant women's
      voices have rarely been heard. Presented here are the results of a qualitative
      study of self-care in pregnancy, birth and lactation with a non-random sample of
      women in British Columbia, Canada. A panel of 27 women was interviewed in the
      third trimester of pregnancy, and 23 of the same participants were re-interviewed
      post-partum (50 interviews in total). Interviews were tape-recorded, transcribed,
      and analyzed thematically. Many of the women said they favoured a natural birth
      and were opposed to labour induction at the time of the first interview. Yet all
      but one of the ten women who went beyond 40 weeks gestation used self-help
      measures to stimulate labour. These women did not perceive prolonged pregnancy as
      a medical problem per se. Rather they saw it as an inconvenience, a worry to
      their friends, families and maternity care providers, and a prolongation of
      physical discomfort. The findings are interpreted by examining the literature on
      the medicalization/healthicization of childbirth.

PMID- 15246170
TI  - Health lifestyles in central Asia: the case of Kazakhstan and Kyrgyzstan.
AB  - There is a growing body of evidence suggesting that negative health lifestyles
      are the principal social determinants of the mortality crisis in the former
      socialist states. Little is known, however, about health lifestyles in Central
      Asia, where the downturn in life expectancy was also experienced. This paper
      examines health lifestyles in Kazakhstan and Kyrgyzstan in order to fill an
      important gap in the literature. The data show, consistent with the improved
      longevity of the Kyrgyz population, that such lifestyles are more positive in
      Kyrgyzstan despite the somewhat better economic situation in Kazakhstan, where
      the mortality crisis continues.

PMID- 15246171
TI  - Analysis of health-related quality of life (HRQL), its distribution, and its
      distribution by income in Japan, 1989 and 1998.
AB  - Research conducted over the past decade has increasingly focused on health
      inequality. The goals of improving the health of a population are now often
      expressed as the increase in the average level of health and the decrease in
      health inequality as clearly specified in the Healthy People 2010 and the World
      Health Report 2000. Using a nationally representative sample of the 1989 and 1998
      waves of the Japanese Comprehensive Survey of Living Conditions of the People on
      Health and Welfare (CSLC), this research examines the average health-related
      quality of life (HRQL), its distribution, and its distribution by income share.
      This study departs from previous health inequality analyses in the following two
      ways: (1) construction of a measure of HRQL in the CSLC and its application to
      health inequality analysis, and (2) inclusion of the dead in health inequality
      analysis using a cross-sectional survey. This study found that between 1989 and
      1998 the average HRQL in Japan slightly reduced (0.005 reduction), its inequality
      by income slightly reduced (0.002 reduction in the difference between the top 20%
      and bottom 20% income share groups), and its inequality measured by the Gini
      coefficient slightly increased (0.002 increase). Women's HRQL was almost always
      lower than men's, except in earlier ages younger than 10 years old. HRQL was more
      unequally distributed among women than men and in older ages. This analysis shows
      that the success in the improvement in the length of life in Japan did not always
      coincide with the improvement in HRQL and provides a basis for the future
      population health research.

PMID- 15246172
TI  - Socioeconomic determinants of mortality in two Canadian provinces: multilevel
      modelling and neighborhood context.
AB  - The influence of individual and contextual socioeconomic variables on mortality
      is compared in two Canadian provinces, Manitoba and Nova Scotia. Although
      differing substantially in size, ethnic mix, and history, both provinces provide
      greater access to health and social services as well as fewer income inequalities
      than the United States. A total of 8032 Manitoba respondents (followed from 1996
      97 to 2002) and 2116 Nova Scotia respondents (followed from 1990 to 1999) were
      linked to the appropriate Canadian census as a source of neighborhood
      characteristics. Data were analyzed using individual- and multi-level logistic
      regression. Well-educated and higher income individuals were less likely to die
      during follow-up. No significant direct effect was found between neighborhood
      socioeconomic characteristics and mortality. However, both provinces showed an
      increased importance of individual income vis-a-vis mortality in advantaged
      neighborhoods relative to disadvantaged neighborhoods. Additional Manitoba
      analyses showed a "healthy mover" effect among respondents changing place of
      residence, regardless of whether they moved to more advantaged or more
      disadvantaged neighborhoods. The findings are discussed in the context of
      differences in health and health care among Canada, the United States, and other
      OECD countries.

PMID- 15246173
TI  - Premature mortality among lone fathers and childless men.
AB  - This study focuses on male family situation and premature mortality. For a total
      of 682,919 men, we analysed mortality from different causes (1991-2000) among
      lone fathers, with and without custody of their children, and among childless
      men, with and without partners. Long-term cohabiting fathers with a child in
      their household were used as comparison group. We employed data from Swedish
      censuses, national health-data registers, and a Swedish register containing
      information about known biological relations between children and parents. We
      investigated the extent to which different kinds of relations were influenced by
      varying socioeconomic circumstances between groups, and also processes of health
      selection. The results suggest that lone non-custodial fathers and lone childless
      men face the greatest increase in risks, especially from injury and addiction,
      and also from all-cause mortality and ischaemic heart disease. Being a lone
      custodial father also entails increased risk, although generally to a much lesser
      extent, and not for all outcomes. The elevated risks found in all the subgroups
      considered diminished substantially when proxy variables to control for health
      selection effects and socioeconomic circumstances were added to the initial
      model. Risks fell most in response to introduction of the socioeconomic
      variables, but health selection also played a major role, mostly in the cases of
      lone non-custodial fathers and lone childless men. However, even following these
      adjustments, significant risk increases, although greatly attenuated, remained
      for all the subgroups.

PMID- 15246174
TI  - Blood and bioidentity: ideas about self, boundaries and risk among blood donors
      and people living with hepatitis C.
AB  - Clinical medicine and biotechnology increasingly utilise and transform human
      bodily tissues in novel ways. Today more and more tissues--blood, whole organs,
      ova, embryos, sperm, skin, bone, heart valves, cellular material, bone marrow and
      corneas--can be transferred between donors and recipients. Hence more and more
      people in developed nations have the experience of giving a fragment of their
      body to another, or receiving such a fragment as part of some kind of therapy.
      These systems for the circulation of tissues raise the question of what we have
      termed 'bioidentity'. Bioidentity describes our common-sense understanding of our
      bodies as 'ours', as both supporting and being included in our social and
      subjective identities. Within this framework, how are we to understand the status
      of detachable bodily fragments like blood, ova or organs? As parts of our bodies
      do they retain a trace of our identity after donation, or are they detachable
      things? What is our relationship, if any, to the patient who receives our tissues
      as part of their treatment? This paper investigates the specific case of blood
      transfusion and donation. It draws upon in depth interviews with 55 people who
      have specific experience with blood. They either have hepatitis C (are HCV+)
      acquired by transfusion or intravenous drug use, or have donated blood or
      received a blood transfusion but are free of hepatitis C (are HCV-). We analyse
      this material according to the themes--Donated Blood as 'Self', Blood as
      Alienable, Blood as Communal Substance, and Contaminated Gifts and the Blood of
      Strangers. We find that, generally speaking the HCV+ and HCV- groups share very
      similar ideas about blood donation and transfusion. For a minority of both
      groups, blood was understood as a decisive site of self irrespective of location,
      but for the remainder donated blood was either ambiguous with regard to identity,
      a shared substance, or not considered to have any lingering relationship to the
      self once given. However both groups regarded blood as strongly imbued with 'risk
      identity'. In particular the HCV+ interviewees regarded their blood as a
      dangerous personal attribute, one that they must be careful to withhold from
      circulation, whereas the blood donors felt obliged to donate their blood
      precisely because they considered it clean and risk free.

PMID- 15246175
TI  - Striving for normalcy: symptoms and the threat of rejection after lung
      transplantation.
AB  - The purpose of this paper is to describe the psychosocial process of the symptom
      experience associated with the threat of organ rejection after lung
      transplantation. A grounded theory approach, including theoretical sampling and
      constant comparative analyses, was used in a sample of 14 lung transplant
      recipients who varied in age, gender, underlying lung disease, experience with
      rejection, and time since transplantation. 'Striving for normalcy' was the core
      process linking each of the four stages of the symptom experience and
      interpretation: naivete, vulnerability, discovery, and insight. Each stage was
      marked by an initiating event, a predictable symptom response, and a dialectic
      (an internal struggle between recipients' personal perceptions of the situation
      and the juxtaposed understandings of the situation that they gleaned from
      transplant clinicians). Each stage was also labeled with a descriptor of the
      aspect of striving for normalcy that accounted for the variation in the symptom
      responses that recipients exhibited, the dialectics they faced, and the exemplars
      for each stage of the process. During the stage of naivete, recipients were
      elated at improvements after transplantation, and often denied or delayed
      reporting symptoms. Once they experienced a rejection episode they entered the
      stage of vulnerability and became more vigilant about symptoms. The discovery
      stage was marked by the realization that rejection lacked characteristic
      symptoms; therefore, it was important to recognize any changes from their
      baseline condition. Recipients who achieved the insight stage realized that until
      they gave up some independence in exchange for interdependence, extended periods
      of normalcy eluded them, and embraced a reciprocal relationship with the
      transplant team. Knowledge that recipients' experience evolves over time from
      furtive hope during the stage of naivete to qualified hope during the insight
      stage, directs us to intervene using stage-specific interventions to promote
      better symptom recognition and reporting.

PMID- 15246176
TI  - Neighbourhood influences on health in Montreal, Canada.
AB  - This paper examines neighbourhood effects on health within a large Canadian city-
      Montreal. Our approach is to consider that individual health outcomes are
      determined both by individual and neighbourhood characteristics and we
      consciously take on the problem of neighbourhood definition by developing
      'natural' neighbourhoods. Our data come from the Montreal health region sample of
      the 2000/1 Canadian Community Health Survey, a comprehensive national survey that
      contains information on health outcomes as well as behavioural and socio
      demographic information. Respondents were placed into 'naturally' defined
      neighbourhoods as opposed to arbitrary geostatistical units, responding to calls
      in the literature to develop more meaningful units of analysis. We also compare
      the 'natural' neighbourhood approach with the use of standard census tracts as
      the unit of analysis. Results show significant between-neighbourhood variation in
      health status with about 3% of the variance in the Health Utilities Index
      captured at the neighbourhood level, even after controlling for a variety of
      socio-demographic and behavioural variables at the individual level. Models using
      census tracts as the unit of analysis had remarkably similar results to the
      'natural' neighbourhood models, suggesting that census tracts are good proxies
      for natural neighbourhood boundaries in studies of neighbourhood effects on
      health.

PMID- 15246177
TI  - The expression of aversion to medicines in general practice consultations.
AB  - Although the relevance of patients' views about medicines for their medicine
      taking behaviour is now well established, little is known about the ways in which
      these views are discussed in primary care consultations. In particular, many
      studies have demonstrated patients' aversion to medicines. This paper examines
      the form that aversion talk takes in the consultation and how doctors respond to
      patients' expression of aversion to medicines. It is based on a dataset of 35
      case studies of general practice consultations in England. In interviews with
      researchers, aversion to medicines was expressed in 34 of the 35 cases. In
      consultations with doctors, aversion was expressed in 10 cases. The interactional
      dimension of aversion talk in consultations was analysed using Conversation
      Analysis, and two general patterns were identified. Aversion could be used as an
      interactional resource, or it could be a topic in its own right. If used as an
      interactional resource, no real discussion of patients' views of medicines took
      place. When aversion was a conversational topic in its own right, two situations
      were observed. Firstly, the doctor elicited patients' views directly. Secondly,
      patients initiated aversive talk using a range of indirect strategies to do so.
      Even when patients managed to express their aversion to medicines, doctors did
      not engage them in any real discussion of their views. A scheme of interpretation
      is suggested to explain these findings. In this scheme patients perceive
      medicines to be an extension of the doctor and to be beneficial. In this view it
      is right for doctors to prescribe medicines and for patients to take medicines.
      The results of this paper suggest that using aversion as an interactional
      resource might be the only safe way for patients to express their aversion
      without seeming to breach the social contract.

PMID- 15246178
TI  - Rapid income growth adversely affects diet quality in China--particularly for the
      poor!
AB  - To study the impact of income change--specifically rapid income growth--on diet
      behavior over time and by socioeconomic level, we used data from a prospective
      study of China begun in 1989 (followed up in 1991, 1993 and 1997). The
      subpopulation used in this study included 5783 subjects aged 20-45 years old from
      3129 households. Dietary intakes were measured using a combination of the
      weighing method and three consecutive 24-h recalls. Detailed income and price
      data were collected, and predicted household per capita income was used in
      multivariate longitudinal random-effects models that described the consumption of
      several food groups and nutrients. Income elasticity was used to measure the
      changes for the effects of income over time on (a) the probability of consuming
      any food and (b) the quantity of food consumed. The structure of the Chinese diet
      is shifting away from high-carbohydrate foods toward high-fat, high-energy
      density foods. The variation in the income effects that we uncovered indicated
      that important changes in income effects took place between 1989 and 1997, with
      the changes varying considerably by socioeconomic status. These shifts in income
      effects indicate that increased income might have affected diets and body
      composition in a detrimental manner to health, with those in low-income groups
      having the largest increase in detrimental effects due to increased income.
      Extrapolating from our estimates, higher income levels in the future could lead
      to the reversal of the health improvements achieved in the last two decades, if
      diet-related noncommunicable diseases cannot be controlled.

PMID- 15246179
TI  - Around-the-clock: parent work schedules and children's well-being in a 24-h
      economy.
AB  - Family life in developed economies has undergone a fundamental change--shifting
      from single-breadwinner households (typical of the post war decades) to families
      where both parents are employed. Equally dramatic has been the emergence of
      around-the-clock economies, altering the way work is organised, especially
      working time. Many more children now live in households where one or both parents
      work non-standard hours (evenings, nights or on weekends). Are there any
      implications for children's well-being when parents work non-standard schedules?
      There has been virtually no investigation of how children are faring in these
      around-the-clock households, despite evidence that non-standard work times affect
      family functioning and are stressful for parents. Using data from a
      representative sample of 4433 dual-earner Canadian families and their 2--11-year
      old children (N children=6361), we compared families where both parents worked
      standard hours, with families where one or both worked non-standard times
      (evenings, nights or weekends). In nearly three-quarters of the families one or
      both parents regularly worked non-standard times. We found associations between
      children's well-being and parent work schedules, with higher odds ratios for
      child difficulties when parents worked non-standard times. These associations
      persisted after adjusting for several confounding factors including socio
      economic status, parent part-time or full-time work, and childcare use, and were
      evident whether mothers, fathers or both parents worked non-standard times. The
      findings raise questions about the implications for children of the 24-h economy.

PMID- 15246180
TI  - Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7
      years of experience.
AB  - Programs implementing community-based directly observed therapy (DOT) have
      demonstrated success in the treatment of patients with tuberculosis. However,
      given complexities in the management and treatment of patients infected with
      multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT
      to treat MDR-TB patients has only recently been successfully attempted. We
      describe the first such program and highlight the crucial components and most
      critical challenges to creating a successful community-based MDR-TB treatment
      program.

PMID- 15246181
TI  - Audience, consequence, and journal selection in toxic-exposure epidemiology.
AB  - Even preliminary toxic-exposure epidemiology papers can spark "media scares" and
      questionable reactions amongst the public. Concerns for the social consequences
      of publication can lead epidemiologists--despite the advantages of visible
      publication--to choose a more obscure outlet for potentially sensitive studies.
      Interviews with 61 US toxic-exposure epidemiologists indicate that investigators
      generally sought visible journals to transmit their work to the widest relevant
      audience. Yet up to 36-46% of this sample sometimes have sought or would seek to
      keep their research from a public who, they feared, might misuse their results.
      Implications for the boundaries between science and society (including evidence
      of hidden scientific activism and "inert" public activism) are discussed, and six
      hypotheses for further research are proposed.

PMID- 15246182
TI  - Governing street-based injecting drug users: a critique of heroin overdose
      prevention in Australia.
AB  - This article provides a critical analysis of existing approaches to the
      prevention of heroin overdose in Australia. It draws on almost 2 years of
      ethnographic research with street-based injecting drug users (IDUs), street-based
      sex workers and service providers in Melbourne, Australia's second largest city,
      and on recent anthropological and sociological work on governmentality. The
      substantive sections of the article argue: (1) that heroin overdose prevention in
      Australia contains implicit or explicit assumptions of rationality and personal
      autonomy, continues to emphasise individual behaviour change and inscribes a self
      disciplined, self-aware, self-regulating subject; and (2) that the social,
      cultural and economic realities--the 'lived experience'--of street-based IDUs and
      sex workers may undermine or hinder the successful adoption of overdose
      prevention strategies. The paper concludes by arguing that the 'chaotic'
      practices of street-based IDUs and sex workers arise in response to particular
      'risk environments', and that individually focused overdose prevention
      strategies, while an important first step, need to be complemented by measures
      addressing the macro- and micro-aspects of risk environments.

PMID- 15246183
TI  - The epidemiology of bronchioloalveolar carcinoma over the past two decades:
      analysis of the SEER database.
AB  - Bronchioloalveolar carcinoma of the lung (BAC) is a subtype of adenocarcinoma of
      the lung. Although traditionally grouped with other non-small cell lung
      carcinomas (NSCLC), BAC has unique morphological features and clinical behavior
      such as bilateral lung involvement, indolent course and lack of association with
      smoking. Some epidemiologic studies report a significant increase in the
      incidence of BAC. We used the SEER database to compare the incidence,
      demographics, and overall survival of BAC patients as compared to other NSCLC
      types over the past two decades (1979-1998). Although the incidence of BAC has
      increased over the past two decades, BAC represents less than 4% of all NSCLC in
      every time period evaluated. The 1 year survival rate is significantly better for
      BAC patients relative to other histological subtypes of NSCLC. There has not been
      a marked increase in the incidence of BAC reported to SEER over the past 20
      years.

PMID- 15246184
TI  - Time trends of lung cancer incidence by histologic types and smoking prevalence
      in Hong Kong 1983-2000.
AB  - The gender difference in epidemiology of lung cancer has been postulated to be
      due to the higher susceptibility of women to risk factors especially tobacco
      smoking. Alternatively, such difference may also be explained by some unknown
      gender-specific etiological factors, which can have been masked if both the
      female and male prevalence of smoking are high. Hong Kong has a low female
      smoking prevalence rate and therefore the trend of the female incidence of lung
      cancer is particularly interesting because it can reflect the effects of the non
      smoking related risk factors more clearly. The present study examined the trends
      of incidence rates for the major histologic types and smoking prevalence from
      1983 to 2000 in Hong Kong with respect to gender. The prevalence of daily smokers
      decreased from 39.7% in 1982 to 22% in 2000 in males and from 5.6 to 3.5% in
      females. The time trends of the lung cancer incidence (overall or with respect to
      age and histology) were similar for both genders. The overall incidence decreased
      progressively throughout the study period, attributable to the decrease in
      squamous cell, small cell and large cell carcinoma. The decline occurred in all
      age groups but to a greater extent in the younger age groups. The incidence of
      adenocarcinoma increased until 1988-1990 and then stabilized. The initial
      increase was restricted to the older age groups. These temporal patterns
      suggested that the same etiological factors affected both genders to a different
      extent but manifested as similar changes in the direction of incidence over time.
      To confirm this hypothesis, further studies were needed to clarify the nature of
      these etiological factors for the non-smoking related lung cancer cases.

PMID- 15246185
TI  - Smoking behavior does not influence the natural course of pre-invasive lesions in
      bronchial mucosa.

PMID- 15246186
TI  - Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes
      in Hong Kong.
AB  - OBJECTIVE: To study the potential role of genetic polymorphisms of glutathione-S
      transferases GSTM1, GSTT1 and GSTP1 in susceptibility to lung cancer in Hong Kong
      Chinese. METHODS: 229 consecutive incident patients with a histological diagnosis
      of lung cancer from a regional hospital and 197 healthy population-based controls
      were recruited for this study between July 1999 and June 2001. Genetic
      polymorphisms of GSTT1 and GSTM1 were determined using PCR-based technique.
      RESULTS: The frequencies of GSTT1 and GSTM1 null genotypes were 51.8 and 59.4% in
      healthy controls and 63 and 54.7%, respectively, in lung cancer patients. GSTP1
      Val105/Val105 genotype was found in only 1% of healthy controls. The risk for
      lung cancer with GSTT1 null genotype was significantly higher, adjusted odds
      ratio (OR) 1.69, 95% confidence interval (CI) 1.12-2.56, compared with those with
      the GSTT1 genotype; the increase in risk was found only in non-smokers. GSTM1
      null genotype, combined GSTT1 and GSTM1 null genotype and GSTP1 Val105/Val105
      genotype did not confer any increase risk for lung cancer. CONCLUSION: GSTT1 null
      genotype is associated with an increased risk for lung cancer in non-smoking
      Chinese in Hong Kong.

PMID- 15246187
TI  - Co-expression of Cox-2 and EGFR in stage I human bronchial adenocarcinomas.
AB  - Cyclooxygenase (Cox)-2 plays an important role in cell proliferation,
      carcinogenesis and tumor growth, in part through the synthesis of prostaglandin
      E2 (PGE2) as well as through other yet unknown routes. Epidermal growth factor
      receptor (EGFR) signaling regulates Cox-2 expression, which has not been
      thoroughly examined in bronchial carcinomas. The current study examined the
      expression of Cox-2, EGFR, P53 and proliferative marker Ki-67 immunoreactivities
      by immunohistochemistry in 71 surgically removed stage I bronchial
      adenocarcinomas. Furthermore, we evaluated the prognostic value of these
      molecules to elucidate the biological significance of Cox-2 expression. Higher
      Cox-2 expression (more than 10% immunoreactivities in tumor cells) was strongly
      associated with higher EGFR and P53 expression as well as a Ki-67 LI above 20% (P
      < 0.01). Cox-2 and EGFR immunoreactive tumor cells showed a similar distribution
      pattern. Five-year survival rate was 73% in 57 cases showing higher Cox-2
      expression and 100% in 14 cases showing lower expression, indicating a
      significant difference in survival (P = 0.040). Higher Cox-2 expression might be
      associated with tumor progression and worse prognosis through EGFR signaling
      interaction in Stage I bronchial adenocarcinomas.

PMID- 15246188
TI  - Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung
      cancers by multiplex real time RT-PCR.
AB  - Extracellular matrix (ECM) homeostasis is strictly maintained by a coordinated
      balance between the expression of matrix metalloproteinases (MMPs) and their
      specific inhibitors (TIMPs). Our study was focused on the simultaneous
      measurement of the expression profile of MMP9 mRNA and its principal inhibitor,
      TIMP-1, in 100 non small cell lung cancers (NSCLC) and in corresponding adjacent
      non malignant tissues. The measurement was performed with a multiplex
      quantitative RT-PCR assay based on TaqMan assay, using two probes labelled with
      different fluorocromes. We found that both MMP9 and TIMP-1 mRNAs were
      significantly higher in NSCLC (P < 0.0001) in comparison to corresponding
      controls as well as the MMP9/TIMP-1 ratio (P = 0.014). MMP9 and TIMP-1 mRNA
      expression was highly correlated in cancer samples (r = 0.73, P < 0.0001). The
      analysis in the two main histotypes revealed a significant increase of MMP9 mRNA
      in adenocarcinomas in comparison to normal tissues (P = 0.006) but not in
      squamous cell carcinomas, while TIMP-1 mRNA showed a significative increase both
      in adenocarcinomas and in squamous cell carcinoma samples (P = 0.02 and 0.01,
      respectively). Both MMP9 and TIMP-1 mRNAs were significantly correlated to
      lymphnode invasion and cancer stage. Survival analysis revealed that high levels
      of expression of MMP9 mRNA, but not of TIMP-1, were significantly associated to
      an unfavourable outcome in NSCLC patients in toto (P = 0.017). In addition our
      results showed that high levels of MMP9 expression are of independent prognostic
      impact in operable NSCLC. Our data seem to demonstrate a simultaneous and
      coordinated up-regulation of MMP9 and TIMP-1 expression at the mRNA level in
      NSCLC, even if this phenomenon seems variable according to the histotype. In
      addition, the increase of MMP9/TIMP-1 ratio may reflect an unbalance of their
      production in affected tissues. The increased expression of the two mRNAs, even
      not necessarily equate their enzymatic activities, seems to parallel a major
      cancer aggressiveness.

PMID- 15246189
TI  - Expression of p53 protein and the apoptotic regulatory molecules Bcl-2, Bcl-XL,
      and Bax in locally advanced squamous cell carcinoma of the lung.
AB  - OBJECTIVE: Bcl-2 family of proteins plays a critical role in the regulation of
      apoptosis. This pathway may be dysregulated leading to an altered ratio of pro-
      and anti-apoptotic molecules, hence rendering cells resistant to chemotherapy.
      The objective of this study was to understand the role of Bcl-2 family members in
      mediation of apoptosis in squamous cell carcinoma of the lung. RESULTS:
      Bronchoscopically obtained lung biopsies from 30 cases of histologically proven
      squamous cell carcinoma of the lung in stage III were assessed for the expression
      of Bcl-2, Bcl-XL, and Bax at the mRNA and protein levels by semi-quantitative
      reverse transcription (RT-PCR) and immunohistochemistry. The apoptotic index (AI)
      was determined by the TUNEL assay. The AI ranged from <0.1 to 6.0% with a median
      of 1.3%. Bcl-2/Bax transcript ratio ranged from 1.5 to 4.5 and Bcl-XL/Bax from
      1.3 to 4.0 indicating increased levels of anti-apoptotic molecules at the
      transcript levels. There was no correlation of the mRNA levels to the apoptotic
      index. (Wilcoxon-signed rank test.) Immunohistochemistry for proteins revealed
      that majority of the tumors were Bax predominated. p53 protein
      immunohistochemical expression was present in 66% cases. The apoptotic index
      correlated with Bax expression (P < 0.05; Wilcoxon-signed rank test and chi
      square test) but not with Bcl-2, Bcl-XL or p53 levels. There was a positive
      association of p53 with Bax expression. CONCLUSION: The results of this study
      indicate that in locally advanced squamous cell carcinoma of the lung, Bax
      protein is up regulated and determines the level of apoptosis.

PMID- 15246190
TI  - Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor
      tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung
      cancer.
AB  - We examined 116 stage I-IIIA non-small-cell lung cancer (NSCLC) patients for
      intra-tumoral expression of thymidylate synthase (TS) and dihydropyrimidine
      dehydrogenase (DPD) using TaqMan reverse transcription polymerase chain reaction
      (RT-PCR) assay to clarify the correlation between gene expression and the
      efficacy of 5-fluorouracil (5-FU) in patients with NSCLC. Patients who were
      administered 5-FU alone after surgery comprised the 5-FU group (n = 30), and
      those who underwent only surgery comprised the control group (n = 86). When
      dichotomized at the mean TS and DPD mRNA level, patients with low-DPD tumors who
      were administered 5-FU had a significantly better prognosis than those who did
      not receive adjuvant treatment (p = 0.041). In addition, in the 5-FU group, 10
      patients with both low-TS and low-DPD tumors have not had any relapse, whereas 8
      of the 20 patients with either high-TS or high-DPD tumors developed distant
      metastasis after surgery. Based on these results, the quantitation of TS and DPD
      mRNA levels may predict the efficacy of 5-FU after surgery for patient with
      NSCLC.

PMID- 15246191
TI  - Increased osteonectin expression is associated with malignant transformation and
      tumor associated fibrosis in the lung.
AB  - Chemical transformation of the SV-40 immortalized bronchial epithelial cell line
      BEAS2-B induces alterations in molecules involved in cell cycle control,
      including up-regulation of EGFR and cyclin E [Oncogene 13 (1996) 1983; Clin
      Cancer Res 8 (2002) 54]. The finding that these changes also occur in vivo, in
      both pre-invasive and invasive lung cancer [Cancer Res 55 (1995) 1365; Cancer Res
      59 (1999) 2470], proves this to be a suitable model to study lung carcinogenesis.
      The current study tested the hypothesis that chemical treatment of BEAS2-B with
      Cigarette Smoke Condensate (CSC) may affect levels of gene products involved in
      cell adhesion and tissue remodeling. To this end, we studied the extent of
      changes in osteonectin (ON) protein levels induced in BEAS 2 B-cells by CSC
      treatment and its timing to changes occurring in the anchorage independent
      cloning efficiency. ON, a multimodular protein component of the extra-cellular
      matrix, has been implicated in tissue remodeling occurring in neoplastic and non
      neoplastic conditions, but its role in lung carcinogenesis is incompletely
      characterized. To validate the in vitro findings, as in our previous reports, we
      studied resected lung tissue, to assess whether ON expression in neoplastic lung
      tissue differs from normal, and to determine its cellular localization. We found
      that CSC treatment of BEAS2-B cells results in a 7-16-fold increase in ON protein
      levels, that is associated with increased colony forming efficiency. ON is absent
      in normal lung; in contrast it is present in the majority (39/52) of non-small
      cell lung cancer (NSCLC). Here, its expression is restricted to peritumoral
      fibroblasts in squamous cell carcinoma and adenocarcinoma. In contrast, it is
      localized to tumor cells in pulmonary sarcomatoid carcinoma (8/10). Thus, up
      regulated ON is linked in vitro to cell transformation and in vivo, it is
      frequently expressed in tumor-associated fibrosis, compatible with its proposed
      role in tissue remodelling. Increased ON expression by tumor cells appears to
      represent a marker of sarcomatoid NSCLC.

PMID- 15246192
TI  - Clinical significance of heparanase activity in primary resected non-small cell
      lung cancer.
AB  - Clinicopathological significances of heparanase activity in non-small cell lung
      cancer (NSCLC) were investigated by analyzing 76 resected specimens of NSCLC.
      Heparanase activities in NSCLC were significantly higher than non-cancerous lung
      tissues (P < 0.0001). The heparanase activities of NSCLC were significantly
      higher in larger diameter tumors (P = 0.0141) or with metastasis to ipsilateral
      mediastinal lymph nodes (P = 0.0004). The activities of heparanase in primary
      tumors were increased significantly according to the pathological stage of the
      progression of the disease (P =0.0009). Among the clinicopathological parameters,
      histological cell type and evidence of ipsilateral lymph node metastasis showed a
      significant association with elevated heparanase activities, whereas age, degree
      of differentiation and tumor diameter did not. Kaplan-Meier curves for overall
      and disease-free survival demonstrated a significant difference between patients
      with elevated and non-elevated heparanase activity by log-rank test (P = 0.0145
      and 0.0002, respectively). Multivariate analysis showed heparanase activity was
      an independent factor to influence disease-free survival in our study. These
      results suggest that heparanase activity could be used as a prognostic indicator
      for postoperative patients with NSCLC and heparanase might be a promising
      molecular target for treatment of NSCLC.

PMID- 15246193
TI  - Prognostic significance of main bronchial lymph nodes involvement in non-small
      cell lung carcinoma: N1 or N2?
AB  - STUDY OBJECTIVES: Accurate TNM staging is the basis to evaluate prognosis and to
      plan treatment of patients with non-small cell lung cancer. Exact definition of N
      status is fundamental and the boundary line between N1 and N2 stations is one of
      the most controversial issue. Purpose of this study is to evaluate the prognostic
      significance of main bronchus nodes, that we classified as station number 10
      (N1). METHODS: We reviewed retrospectively lymph node patterns and survival of
      175 patients with N1 and 154 with N2 disease, that underwent surgical resection
      with hilar and mediastinal lymphadenectomy from January 1990 to December 2000.
      These two groups were subdivided in N1 without station number 10 involvement (N1
      , n = 144), N1 with station number 10 involvement (N1+, n = 31), N2 single
      station (N2s, n = 107) and N2 multiple stations (N2m, n = 47), respectively. A
      univariate and multivariate analysis of prognostic factors predicting survival
      has been performed. RESULTS: Overall 5-year survival rate for 175 N1 patients and
      154 N2 patients was 42 and 13%, respectively and the difference was statistically
      significant (P < 0.001). The prognosis between N1-, N1+, N2 was compared: 5-year
      survival rate was 44, 31 and 13%, respectively and the difference reached a
      statistical value between N1+ and N2 (P < 0.05), but not between N1- and N1+.
      When the comparison was made with N1-, N1+, N2s and N2m, the difference was
      significant between N1- and N2s (P = 0.0003), between N1+ and N2m (P = 0.0001),
      but not between N1+ and N2s. CONCLUSIONS: The aim of a uniform anatomical and
      clinical classification of nodal stations has not been thoroughly achieved,
      particularly regarding the boundary line between N1 and N2. Our study points out
      that the involvement of main bronchial nodes has a prognostic significance
      similar to that of N2 single station and should be considered as an early N2
      disease.

PMID- 15246194
TI  - Single agent gefitinib as first line therapy in patients with advanced non-small
      cell lung cancer: Washington University experience.
AB  - Gefitinib has modest activity with an overall response rate of 11-18% in patients
      with metastatic non-small cell lung cancer (NSCLC) who have had progressive
      disease following platinum containing chemotherapy. However, the efficacy of
      gefitinib in previously untreated metastatic NSCLC is not known. We
      retrospectively analyzed the efficacy of gefitinib as a first line therapy in 26
      patients with advanced NSCLC enrolled in the expanded access program. Patients
      received gefitinib 250 mg a day orally if they had a poor performance status (PS)
      or if they refused cytotoxic chemotherapy. Treatment was continued as long as
      there was no evidence of disease progression or unacceptable treatment related
      toxicities. The characteristics of 25 evaluable patients enrolled between the
      period of May 2001 and August 2002 include: 15 women, 10 men; median age 73 years
      (range 56-86), 81% had an ECOG performance status of two. Only one patient had a
      partial response and 32% had stable disease as their best response for a disease
      control rate of 36%; 32% of patients had disease control lasting 5 months or
      longer. The median overall survival and progression-free survival (PFS) were 14.1
      and 2.9 months, respectively. Toxicities were minimal and included rash and
      diarrhea. Gefitinib was well tolerated and had interesting activity in previously
      untreated patients with advanced NSCLC.

PMID- 15246195
TI  - Second-line weekly paclitaxel in patients with inoperable non-small cell lung
      cancer who fail combination chemotherapy with cisplatin.
AB  - This phase II study was designed to assess single-agent paclitaxel (Taxol), as
      second-line chemotherapy. ELIGIBILITY CRITERIA: pathological diagnosis of
      inoperable non-small cell lung cancer (NSCLC) relapsing or refractory to standard
      front-line platinum (P)-based chemotherapy, performance status < or = 3, normal
      lab tests, informed consent. Ineligibility criteria: history of second or third
      cancer (unless surgically cured), mental instability or impairment, pre-existing
      moderate/severe peripheral neuropathy, previous chemotherapy non-including
      cisplatin, and previous second-line chemotherapy. Paclitaxel was given by
      intravenous infusion at a dose of 100 mg/m2 every week, until completion of the
      treatment plan of 21 weeks, disease progression, persistent toxicity, or patient
      refusal. Thirty-eight patients (32 males) entered the study; median age was 63
      years (range 44-74); cell types were: adenocarcinoma (20), squamous (14), large
      cell (4). Previous chemotherapies: P and vinorelbine (31 patients) and P,
      mitomycin C and vinblastine (7 subjects), followed by 21 objective responses. Two
      patients had one course of paclitaxel; six other patients had early treatment
      suspensions. The median number of weekly infusions was 12 (range 1-21); median
      dose-intensity was 75% of projected. Toxicity was generally mild, mainly
      neurological and never life threatening (only 2 grade 4 toxicity out of 468 pre
      chemotherapy evaluations). Six patients obtained a partial response; 7 others
      showed some tumor regression, 3 had tumor stabilization, and 13 disease
      progression. From the start of paclitaxel, the estimated median time to
      progression was 20 weeks, the median survival 58 weeks. Second-line treatment
      with single-agent paclitaxel is well-tolerated, active, and associated to long
      survivals.

PMID- 15246196
TI  - CT-planned accelerated hypofractionated radiotherapy in the radical treatment of
      non-small cell lung cancer.
AB  - Surgery is the standard treatment for stage I, II and certain stage IIIA non
      small cell lung cancers (NSCLC). A proportion of patients with technically
      operable NSCLC do not undergo surgery because of significant co-morbidity or
      refusal, and radical radiotherapy may cure some of these patients. Between April
      1997 and March 2000, 135 consecutive patients with stage I-IIIB NSCLC were
      treated with CT-planned accelerated hypofractionated radical radiotherapy to a
      dose of 50-55Gy in 15-20 fractions over 3-4 weeks at a single centre. The 2-year
      overall and cause-specific survival for all patients was 44.4% (95% CI = 36.8,
      53.7) and 47.8% (95% CI = 39.9, 57.3) respectively. Overall median survival was
      21 months (95% 18, 28). There were no reports of severe acute or late treatment
      related toxicities. These results compare favourably with previously published
      studies on radical radiotherapy in NSCLC, suggesting this may be an effective and
      safe technique.

PMID- 15246197
TI  - A phase I/II trial of induction chemotherapy with carboplatin and gemcitabine
      followed by concurrent vinorelbine and paclitaxel with chest radiation in
      patients with stage III non-small cell lung cancer.
AB  - PURPOSE: We designed a phase I/II trial in order to evaluate the efficacy and
      tolerability of induction carboplatin and gemcitabine and the maximum tolerated
      dose (MTD) and dose-limiting toxicity (DLT) of subsequent chemoradiotherapy with
      weekly vinorelbine and paclitaxel in patients with stage III non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Patients had pathologically confirmed N2-N3
      stage NSCLC, adequate end-organ function, and ECOG performance status 0-2.
      Carboplatin was administered at an AUC of 5 on day 1 and gemcitabine 1000 mg/m2
      on days 1 and 8, every 21 days, for two cycles, followed by weekly vinorelbine 10
      15 mg/m2 and paclitaxel 50 mg/m2 and conventional chest radiotherapy up to 66 Gy.
      Patients with resectable disease underwent thoracotomy after 40-45 Gy. RESULTS:
      Thirty-nine eligible patients were enrolled; 17 had stage IIIB NSCLC. Grade 3
      esophagitis developed in 4/5 patients on the second dose level of
      chemoradiotherapy (i.e. vinorelbine 15 mg/m2) and was considered dose-limiting.
      Of 34 patients treated at the maximum tolerated dose (i.e. vinorelbine 10 mg/m2),
      2 patients (6%) had pneumonitis >grade 2 and 3 (9%), esophagitis >grade 2.
      Induction chemotherapy was well tolerated with only one patient developing >grade
      2 non-hematologic toxicity (nausea). Forty-one percent of patients had an
      objective response after induction chemotherapy and 51% after chemoradiotherapy.
      Nineteen patients, 16 of whom had stage IIIA, underwent surgical resection. The
      pathologic complete response rate was 16% (42% in the mediastinal lymph nodes).
      With a median follow-up of 31 months, the 3-year progression-free survival (PFS)
      and overall survival (OS) rates were 23 and 34%, respectively, and the median OS
      was 25 months. CONCLUSIONS: We identified a well-tolerated and active
      chemoradiotherapy regimen. Survival results are promising and the addition of a
      biologic agent to this regimen is of interest.

PMID- 15246198
TI  - Phase II study of docetaxel and carboplatin as second-line treatment in NSCLC.
AB  - Aim of this study was to evaluate activity and toxicity of docetaxel and
      carboplatin as second-line treatment in advanced non-small-cell lung cancer
      (NSCLC) patients who failed or relapsed after previous chemotherapy. Patients had
      to have unresectable stage IIIb or IV NSCLC, previous chemotherapy, a performance
      status < or = 2, a normal bone marrow reserve, and an adequate renal and liver
      function. Treatment consisted of docetaxel 75 mg/m2 and carboplatin AUC 6 mg/ml
      min administered every 3 weeks for a maximum of 5 cycles. Fifty-seven patients
      with a median age of 57 years were included. Prior treatment consisted of
      gemcitabine alone (n = 2) or gemcitabine in combination with cisplatin (n = 26)
      or epirubicin (n = 29). Median number of cycles for carboplatin and docetaxel was
      4. Granulocytopenia and thrombocytopenia common toxicity criteria (CTC) grades 3
      and 4 occurred in 79 and 30% of patients, respectively. Febrile neutropenia
      occurred in eight patients (14%), of whom two patients died. Fatigue grades 2 and
      3 occurred in 42% of patients. Other non-haematological toxicity was mild. Tumour
      response rate was 37%, irrespective of the previous regimen. Median survival was
      31 weeks, 1-year survival was 32%. In conclusion, the combination of docetaxel
      and carboplatin is active as second-line treatment in platinum and non-platinum
      pre-treated patients.

PMID- 15246199
TI  - Complete spontaneous remission of non-small-cell lung cancer: a case report.
AB  - Spontaneous remission (SR) of cancer is a rare event, particularly in lung
      cancer. We report the case of a 68-year-old man, who came to our attention with a
      diagnosis of poorly differentiated pulmonary adenocarcinoma and, in absence of
      any active therapy, underwent a durable complete SR. Our case supports the rare
      occurrence of SR in non-small-cell lung cancer (NSCLC).

PMID- 15246200
TI  - Prevention and treatment of hepatitis C virus recurrence after liver
      transplantation.

PMID- 15246201
TI  - Nitric oxide from rat liver sinusoidal endothelial cells induces apoptosis in IFN
      gamma-sensitized CC531s colon carcinoma cells.
AB  - BACKGROUND/AIMS: Investigation of apoptosis is pivotal in searching for
      mechanisms that eliminate colon cancer cells getting trapped in liver sinusoids
      at the time of surgical removal of the primary tumor. This study focuses on
      nitric oxide (NO), Fas/FasL and the involvement of interferon-gamma (IFNgamma) in
      liver sinusoidal endothelial cells (LSECs) and in the colon carcinoma cell line
      CC531s. METHODS: Apoptosis was quantified and visualized in vitro by specific DNA
      fragmentation, specific staining and electron microscopy. In vivo experiments
      were also conducted. RESULTS: In co-cultures of LSECs with CC531s, apoptosis of
      CC531s was observed only when they were pre-treated with IFNgamma, and was
      unaffected by blocking the Fas/FasL pathway. However, LSECs continuously produced
      NO, and apoptosis was inhibited by NO-inhibitors (NMMA and dexamethasone). When
      IFNgamma-sensitized CC531s were injected into rats, liver weight was lower, in
      contrast to control conditions where liver weight was higher. CONCLUSIONS: (i)
      LSECs induce apoptosis in IFNgamma-sensitized CC531s in vitro; (ii) LSECs express
      FasL; (iii) Fas on CC531s becomes active after IFNgamma-treatment; however, (iv)
      blocking the Fas/FasL pathway had no effect; (v) apoptosis was inhibited by NO
      inhibitors; (vi) the immune system uses this IFNgamma-activated pathway to
      support LSECs in killing tumor cells.

PMID- 15246202
TI  - Inverse association between serum adiponectin level and transaminase activities
      in Japanese male workers.
AB  - BACKGROUND/AIMS: Since a novel polypeptide named adiponectin was shown to prevent
      the development of steatosis and steatohepatitis in animal models, we studied
      whether it was also possible in a clinical situation. METHODS: Associations
      between serum adiponectin levels and serum transaminase activities were studied
      in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV-
      or HCV-induced liver diseases. RESULTS: Various markers of metabolic diseases
      including levels of body mass index (BMI), serum triglyceride, total cholesterol,
      and insulin resistance assessed by the homeostasis model were significantly
      higher in subjects with increased transaminase activities when compared to those
      with normal activities. Single regression analyses demonstrated that the
      logarithmic serum adiponectin level was inversely correlated with the levels of
      logarithmic serum AST (r=-0.229, P<0.0001), ALT (r=-0.305, P<0.0001), and
      gammaGTP (r=-0.278, P<0.0001). Even in multiple regression analyses in which
      subjects' age and levels of BMI, serum triglyceride, total cholesterol, and
      insulin resistance were adjusted, the inverse correlations were significant
      (P=0.0426, 0.0332, and 0.0011, respectively). CONCLUSIONS: Hypoadiponectinemia
      may worsen liver diseases associated with metabolic diseases in clinical cases.
      In addition to aggravation of insulin resistance and hyperlipidemia, some
      hypoadiponectinemia specific mechanisms may stand behind the association.

PMID- 15246203
TI  - Alcohol and cirrhosis: dose--response or threshold effect?
AB  - BACKGROUND/AIMS: General population studies have shown a strong association
      between alcohol intake and death from alcoholic cirrhosis, but whether this is a
      dose-response or a threshold effect remains unknown, and the relation among
      alcohol misusers has not been studied. METHODS: A cohort of 6152 alcohol misusing
      men and women aged 15-83 were interviewed about drinking pattern and social
      issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis
      mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this
      large prospective cohort study of alcohol misusers there was a 27 fold increased
      mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from
      alcoholic cirrhosis in women compared to the Danish population. Number of drinks
      per day was not significantly associated with death from alcoholic cirrhosis,
      since there was no additional risk of death from alcoholic cirrhosis when
      exceeding an average daily number of five drinks (>60 g/alcohol) in neither men
      nor women. CONCLUSIONS: The results indicate that alcohol has a threshold effect
      rather than a dose-response effect on mortality from alcoholic cirrhosis in
      alcohol misusers.

PMID- 15246204
TI  - Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease.
AB  - BACKGROUND/AIMS: CD4(+) lymphocytes constitutively expressing the IL-2-receptor
      alpha-chain (CD25) regulate the activation of CD4 and CD8 autoreactive T-cells by
      suppressing their proliferation and effector function. The aim of this study is
      to: (1) measure the percentage of CD4(+)CD25(+) T-cells (T-regs) in patients with
      autoimmune liver disease at presentation and during remission, (2) correlate
      their frequency with disease activity, (3) determine their ability to expand and
      (4) to inhibit interferon-gamma (IFNgamma) production by CD4(+)CD25- T-cells.
      METHODS: 41 patients were studied. Percentage of T-regs was determined on
      peripheral blood mononuclear cells (PBMCs) by triple-colour flow cytometry; their
      ability to expand by exposing PBMCs to a T-cell expander (CD3/CD28 Dynabeads);
      their immunoregulatory function by measuring their ability to suppress IFNgamma
      production by CD4(+)CD25(-) T-cells. RESULTS: T-regs were significantly less in
      patients than in controls, and at diagnosis than during remission. Their
      percentage was inversely correlated with titres of anti-liver kidney microsomal
      and soluble liver antigen autoantibodies. T-regs ability to expand was
      significantly lower in patients than in controls, but that to suppress IFNgamma
      production by CD4(+)CD25(-) T-cells was maintained. CONCLUSIONS: Decreased T-regs
      numbers and ability to expand may favour the emergence of liver-targeted
      autoimmunity, despite preserved suppressor function. Treatment should aim at
      increasing T-regs number.

PMID- 15246205
TI  - Normal protein diet for episodic hepatic encephalopathy: results of a randomized
      study.
AB  - BACKGROUND/AIMS: Protein-restricted diets are usually prescribed for cirrhotic
      patients with hepatic encephalopathy. However, protein restriction may worsen the
      nutritional status without resulting in an improvement of hepatic encephalopathy.
      We designed a study to assess the effects of the amount of protein in the diet on
      the evolution of episodic hepatic encephalopathy. METHODS: Cirrhotics admitted to
      the hospital because of an episode of encephalopathy (n=30) were randomized to
      receive a low-protein diet with progressive increments or a normal protein diet
      for 14 days, in addition to standard measures to treat hepatic encephalopathy.
      Protein synthesis and breakdown were studied at day 2 and day 14 with the glycine
      N(15) infusion method. RESULTS: The outcome of hepatic encephalopathy was not
      significantly different between both groups of treatment. Protein synthesis was
      similar for low and normal protein diet, but those of the low-protein diet group
      showed higher protein breakdown. CONCLUSIONS: Diets with a normal content of
      protein, which are metabolically more adequate, can be administered safely to
      cirrhotic patients with episodic hepatic encephalopathy. Restriction of the
      content of protein of the diet does not appear to have any beneficial effect for
      cirrhotic patients during an episode of encephalopathy.

PMID- 15246206
TI  - Increased apoptosis dependent on caspase-3 activity in polymorphonuclear
      leukocytes from patients with cirrhosis and ascites.
AB  - BACKGROUND/AIMS: Patients with decompensated cirrhosis are prone to develop
      neutropenia. Although hypersplenism and increased clearance of polymorphonuclear
      leukocytes (PMN) in the spleen are thought to contribute to neutropenia in these
      patients, other factors cannot be excluded. The aim of the current study was to
      investigate whether the presence of increased PMN apoptosis could also contribute
      to the appearance of neutropenia in these patients. METHODS: PMN were isolated by
      Ficoll-Hypaque gradient centrifugation from 17 patients with decompensated
      cirrhosis (CH group) and 13 patients with compensated chronic liver disease (CT
      group). PMN were incubated in RPMI 1640 medium at 37 degrees C in a 5% CO(2)
      atmosphere and viability and frequency of apoptosis were evaluated after 0, 10,
      20 and 40 h of culture. Viability was determined by the MTT assay and apoptosis
      by microscopic examination of cell morphology (Diff-Quik staining), DNA
      fragmentation by agarose gel electrophoresis (DNA laddering) and caspase-3
      activity by DVDE-p-nitroanilide cleavage. RESULTS: Compared to CT patients, PMN
      isolated from CH patients exhibited a decreased PMN viability and a marked
      accelerated apoptosis as revealed by an increased number of condensed nuclei,
      increased DNA laddering and significantly higher caspase-3 activity. CONCLUSIONS:
      These findings indicate that shortening of PMN survival via apoptosis may explain
      in part the neutropenia present in decompensated cirrhotic patients with ascites,
      thus favoring the development of bacterial infections in these patients.

PMID- 15246207
TI  - Intestinal glutaminase activity is increased in liver cirrhosis and correlates
      with minimal hepatic encephalopathy.
AB  - BACKGROUND/AIMS: We performed the current study to assess the intestinal activity
      of enterocyte phosphate-activated glutaminase (PAG) in cirrhosis. METHODS: Forty
      nine cirrhotic patients and 36 control subjects underwent endoscopic duodenal
      biopsies. Minimal hepatic encephalopathy (MHE) was evaluated using three
      psychometric tests. Oral glutamine challenge (OGC) was performed and MELD, Child
      Pugh and the presence of esophageal varices were recorded. PAG was measured by
      enzymatic methods. Cerebral magnetic resonance spectroscopy was performed in 10
      cirrhotics. RESULTS: PAG was found to be higher in cirrhotics than control
      subjects 2.4+/-1.51 vs. 0.68+/-0.57IU/mg protein (P<0.001). PAG was also
      increased in patients with MHE and correlated with MELD, INR, esophageal varices
      and serum bile acids. A negative correlation was observed between PAG activity
      and intra-cerebral choline/creatine ratio (r=-0.67; P=0.035) and a positive
      correlation with glutamine plus glutamate/creatine ratio (r=0.78; P=0.007). In
      multivariate analysis using backward logistic regression, presence of MHE was the
      only variable independently related to altered enterocyte PAG. CONCLUSIONS:
      Enterocyte PAG is increased in cirrhotic patients and correlates with MHE. These
      data support a possible role for intestinal glutaminase in the pathogenesis of
      hepatic encephalopathy (HE) and could be a new target for future therapies.

PMID- 15246208
TI  - Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human
      alcoholic cirrhosis.
AB  - BACKGROUND/AIMS: The liver plays a prominent role in the metabolism of asymmetric
      dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO)
      synthase. This study was designed to determine whether plasma levels of ADMA and
      NO production are altered in patients with compensated and decompensated
      alcoholic cirrhosis. METHODS: Plasma levels of l-arginine, ADMA, symmetric
      dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine
      patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with
      advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls.
      RESULTS: ADMA and NOx concentrations in decompensated cirrhosis were higher than
      in the compensated group and control group (ADMA: 1.12+/-0.08 vs. 0.58+/-0.05 and
      0.58+/-0.07micromol/l, respectively; P<0.05; NOx 97.90+/-10.27 vs. 37.42+/-3.91
      and 40.43+/-5.30micromol/l, respectively; P<0.05). There was a positive
      correlation between the clinical score of the patients and concentrations of ADMA
      (r(2)=0.547, P<0.01) and NOx (r(2)=0.689, P<0.01). SDMA and l-arginine levels
      were not significantly different between the three groups. CONCLUSIONS: The
      results suggest that hepatocellular damage is a main determinant of elevated ADMA
      concentration in advanced alcoholic cirrhosis. By inhibiting NO release from
      vascular endothelium, ADMA might oppose the peripheral vasodilation caused by
      excessive NO production in severe cirrhosis.

PMID- 15246209
TI  - Transforming growth factor-beta induces contraction of activated hepatic stellate
      cells.
AB  - BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) is a cytokine
      produced in abundance during liver injury. Recognizing the prominent roles that
      hepatic stellate cells (HSCs) and TGF-beta play in portal hypertension and
      fibrogenesis, respectively, we sought to evaluate the effect of TGF-beta on the
      contractility of activated HSCs. METHODS: Spontaneous immortalized cell lines of
      HSC origin were used in this study. Cells were grown in three-dimensional
      collagen gel lattice, transferred to 60 mm dishes and exposed to varying
      concentrations of TGF-beta1 in serum-free medium at 37 degrees C for up to 120 h.
      The area of the floating gels was measured using a Fluor S-MultiImager (Biorad),
      the cellular smooth muscle-alpha actin (SMA) content quantified and PKC
      activation studies conducted. RESULTS: TGF-beta1 induced a time- and dose
      dependent decrease in lattice area up to 40% of control (P<0.05) that reflects
      the contraction of activated HSCs. This induced contraction was associated with
      increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in
      these cells. Furthermore, pre-incubating with a PKC--specific inhibitor
      completely abrogated the TGF-beta-induced contraction. CONCLUSIONS: TGF-beta
      induces contraction of activated HSCs via an increase in SMA content and a PKC-
      mediated pathway.

PMID- 15246210
TI  - Phenprocoumon-induced liver disease ranges from mild acute hepatitis to (sub-)
      acute liver failure.
AB  - BACKGROUND/AIMS: Except for bleeding complications, other serious adverse
      reactions of coumarin anticoagulants such as hepatotoxicity or skin necrosis are
      comparatively rare. Nonetheless, a small number of coumarin-induced (sub-) acute
      liver failures has been published. METHODS: A retrospective analysis was
      performed of patients treated for liver disease between 1992 and 2002 at our
      department to evaluate the incidence, clinical findings and histopathology of
      coumarin-induced hepatotoxicity. RESULTS: The retrospective analysis revealed
      eight cases of phenprocoumon-induced hepatotoxicity, including three cases of
      (sub-) acute liver failure which resulted in two orthotopic liver
      transplantations and one fatal outcome. Five patients with phenprocoumon-induced
      hepatitis recovered well after anticoagulation was switched to another coumarin
      derivate or subcutaneous low molecular weight heparin. In all patients liver
      injury was predominantly of an hepatitic type. In the cases of (sub-) acute liver
      failure massive confluent liver cell necroses were histologically present,
      whereas among patients without liver failure mild portal to moderate active
      lobular hepatitis were observed. A retrospective analysis by BfArM (German
      Federal Institute for Drugs and Medical Devices) revealed 4390 cases of possible
      phenprocoumon-related adverse reactions since 1990, 2% of which had presented
      with hepatitis and 0.2% with liver failure. CONCLUSIONS: Phenprocoumon-induced
      liver disease is an uncommon complication, which can, however, cause (sub-) acute
      liver failure.

PMID- 15246211
TI  - Reduction and expansion of the glutamine synthetase expressing zone in livers
      from tetracycline controlled TGF-beta1 transgenic mice and multiple starved mice.
AB  - BACKGROUND/AIMS: To learn more about tissue remodelling in fibrotic livers of
      tetracycline-controlled TGF-beta1 transgenic mice (TGF-beta1-on-mice) and during
      regeneration after removal of the fibrotic stimulus (off-mice), we investigated
      the expression of glutamine synthetase (GS), an exclusive pericentrally expressed
      enzyme. METHODS: GS was localised immunohistochemically and quantified by real
      time RT-PCR and enzymatic activity measurement. Apoptosis in livers of TGF-beta1
      on-mice was demonstrated by in situ apoptosis detection kit (TUNEL reaction).
      RESULTS: Livers of TGF-beta1-on-mice harbour a reduced number of GS-positive
      hepatocytes and expression of GS is downregulated, while multiple starved mice
      serving as controls for malnutrition during TGF-beta1 exposure surprisingly
      showed an impressive amplification of GS-positive hepatocytes. Apoptotic events
      were frequent around central veins in livers of TGF-beta1-on-mice, while in
      multiple induced mice apoptosis was dominant around all vessels and weak in
      midzonal areas. During regeneration from fibrosis, control levels were regained
      within 21 days. Beta-catenin was dislocated from plasma membrane to cytoplasm
      exclusively in pericentral hepatocytes during a short time slot after a unique
      expression of TGF-beta1. CONCLUSIONS: Reduction of GS in TGF-beta1-on-mice
      results from apoptosis of GS-positive hepatocytes rather than downregulation of
      GS expression. Beta-catenin seems involved in the recovery of GS-positive
      hepatocytes.

PMID- 15246212
TI  - Impairment of mitochondrial oxidative phosphorylation in rat fatty liver exposed
      to preservation-reperfusion injury.
AB  - BACKGROUND/AIMS: As the impairment of the cellular energy metabolism contributes
      to the failure of fatty liver grafts after transplantation, we aimed to determine
      whether steatosis affects the oxidative phosphorylation activity during
      preservation. METHODS: Rat normal and fatty livers were preserved for 18 h and
      then reperfused with warm oxygenated solution. The oxidative phosphorylation, the
      F(0)F(1)-ATPase and the Complex I activities were assessed in isolated
      mitochondria before and after preservation, and during reperfusion. The ALT
      release and portal pressure were monitored during reperfusion. RESULTS: The
      baseline phosphorylation activity was similar in normal and steatotic
      mitochondria. After cold preservation, the respiratory control index and state 3
      respiration decreased significantly only in steatotic livers. Reperfusion induced
      a further deterioration in either group. Contrary to normal liver, uncoupling of
      fatty liver mitochondria allowed the recovery of the maximal respiration rate
      only using succinate (Complex II-dependent substrate), but not glutamate-malate
      (Complex I-dependent). Complex I dysfunction was confirmed
      spectrophotometrically. The ATPase activity was also significantly lower in fatty
      livers. Finally, ALT release and portal pressure were greater in steatotic
      livers. CONCLUSIONS: The alteration of the oxidative phosphorylation activity
      during preservation is greatly exacerbated by fatty infiltration likely resulting
      from damage of the respiratory chain Complex I and of the F(0)F(1)-ATP synthase.

PMID- 15246213
TI  - Prophylactic phenytoin does not improve cerebral edema or survival in acute liver
      failure--a controlled clinical trial.
AB  - BACKGROUND/AIMS: Seizure activity in patients with acute liver failure (ALF) may
      increase cerebral oxygen requirements and worsen cerebral edema. Recently,
      prophylactic phenytoin has been recommended to suppress sub-clinical seizure
      activity evident on electroencephalographic monitoring. To determine the clinical
      utility of prophylactic phenytoin therapy in patients with ALF. METHODS: Forty
      two patients with ALF were randomized. Twenty two patients were given
      prophylactic phenytoin and 22 patients acted as controls. The baseline clinical
      and biochemical features were similar in the two groups and patients with > or =2
      poor prognostic variables were equally represented. RESULTS: Sixteen patients in
      the phenytoin group, and 15 in the control group developed cerebral edema
      (P=0.38). Mechanical ventilation was required in 10 and 12 patients in the
      phenytoin and control groups, respectively, (P=0.77). Seizures occurred in 5
      (22.7%) control patients and 5 (25%) phenytoin treated patients (P=0.86).
      Fourteen (70%) patients randomized to phenytoin and 15 (68.2%) control patients
      died (P=0.89). CONCLUSIONS: Seizure was common in patients with ALF. Prophylactic
      use of phenytoin did not prevent cerebral edema, seizures or need for mechanical
      ventilation, and did not improve survival.

PMID- 15246214
TI  - Involvement of the vascular endothelial growth factor receptor-1 in murine
      hepatocellular carcinoma development.
AB  - BACKGROUND/AIMS: The role of the vascular endothelial growth factor receptor-1
      (VEGFR-1) in hepatocellular carcinoma (HCC) development has not been elucidated
      yet. The aim of this study was to examine the role of VEGFR-1 in VEGF-mediated
      HCC development and angiogenesis as compared to that of VEGFR-2. METHODS: We
      examined the effects of VEGFR-1, and VEGFR-2 neutralizing monoclonal antibodies
      (R-1mAb and R-2mAb, respectively) on VEGF-mediated HCC development both in an
      allograft and orthotopic models. RESULTS: In the allograft model, both R-1mAb and
      R-2mAb significantly attenuated the VEGF-mediated tumor development in a dose
      dependent manner with associated reduction of angiogenesis in the tumor. The
      inhibitory effect of R-2mAb was more potent than that of R-1mAb, and the
      combination treatment with both mAbs almost completely attenuated VEGF-mediated
      HCC development. Immunohistochemical analysis revealed that apoptosis increased
      markedly in the tumor. Furthermore, these inhibitory effects with both mAbs were
      achieved even on established tumors and orthotopic transplantation. CONCLUSIONS:
      In addition to VEGFR-2, VEGFR-1 also lies on the signal transduction pathway by
      which VEGF augments HCC development and angiogenesis not only at the initial
      stage but also in the established tumor.

PMID- 15246215
TI  - Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be
      served as an independent prognostic factor.
AB  - BACKGROUND/AIMS: The development of human malignancies can be attributed to
      aberrant regulation of intracellular signal transduction pathways. In the current
      study, we aimed to evaluate focal adhesion kinase (FAK), a non-receptor tyrosine
      kinase, expression in hepatocellular carcinoma (HCC), and to explore the
      prognostic significance of FAK. METHODS: We investigated FAK mRNA expression in
      60 HCC specimens using quantitative real-time reverse transcription polymerase
      chain reaction analysis, and the correlation between FAK expression and
      clinicopathologic parameters. FAK protein expression was examined using Western
      blot analysis and an immunohistochemical study. RESULTS: We found that FAK mRNA
      was overexpressed in HCCs compared with the corresponding non-cancerous liver
      tissues (P=0.0008). The FAK overexpression correlated significantly with tumor
      size (P=0.034) and serum AFP level (P=0.030). Univariate and multivariate
      analyses revealed that FAK mRNA expression was an independent prognostic factor
      for disease-free (risk ratio 3.83; P=0.024) and overall (risk ratio 7.14;
      P=0.015) survival. Besides, we confirmed immunohistochemically that the FAK
      protein was detectable in cancer cells despite non-expression in corresponding
      non-cancerous tissues. CONCLUSIONS: Our results suggest that FAK mRNA expression
      has prognostic significance for the survival of patients with HCC.

PMID- 15246216
TI  - Differential expression of somatostatin receptor subtypes in hepatocellular
      carcinomas.
AB  - BACKGROUND/AIMS: Somatostatin analogues inhibit cell proliferation by stimulation
      of distinct somatostatin receptor (SSTR) subtypes. In recent years, these
      compounds have been introduced into the therapy of advanced hepatocellular
      carcinoma (HCC). The efficacy of this treatment is under debate due to the
      controversial results of clinical trials. Despite the widespread clinical use of
      somatostatin analogues in HCC, little is known about the expression of each of
      the five SSTRs in these tumors. METHODS: We analyzed the expression of SSTR
      subtypes in 56 HCCs by immunohistochemistry using subtype-specific antibodies.
      Six of the samples were also investigated by RT-PCR using subtype-specific
      oligonucleotide primers. RESULTS: HCCs display differential, individual
      expression patterns as well as variable expression levels for SSTRs. The overall
      expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 is 46, 41, 64, 0, and
      75%, respectively. No significant correlation was observed between SSTR
      expression and tumor stage, differentiation, histological tumor type, or
      underlying liver disease. CONCLUSIONS: Individual patterns and levels of SSTR
      expression might determine the response to treatment with somatostatin analogues
      in HCC. Selective treatment of these tumors based on the analysis of SSTR subtype
      expression might lead to an increase in response rates.

PMID- 15246217
TI  - Epidemiological study of hepatitis B virus genotypes, core promoter and precore
      mutations of chronic hepatitis B infection in Hong Kong.
AB  - BACKGROUND/AIMS: We conducted a population study to document the prevalence of
      hepatitis B virus (HBV) genotypes in Hong Kong. METHODS: HBV genotypes, core
      promoter (CP) and precore mutations were determined in 776 asymptomatic patients.
      RESULTS: 92.6% patients had single genotype [B (32.5%), C (62.5%)]. 99.1% of
      genotype B was subtype Ba. Patients with age <50 years had a lower prevalence of
      genotype B than patients with age >51 years (32.5% vs. 41%, respectively,
      P=0.028). Compared to patients with genotype C, patients with genotype B had a
      higher cumulative rate (P=0.018) and younger age (40.1 vs. 34.2 years,
      respectively, P=0.018) of HBeAg seroconversion. There were no differences in the
      HBV DNA levels between patients with genotypes B and C, and with wild-type and
      mutants of CP and precore regions. By multivariate analysis, patients with
      genotype C and with CP mutations had higher alanine aminotransferase (ALT)
      levels. CONCLUSIONS: B and C were the two most common HBV genotypes in Hong Kong.
      The former had a higher chance of earlier HBeAg seroconversion and lower ALT
      levels. The prevalence of genotype B was lower in patients with age <50, probably
      related to influx of immigrants from China since 1949.

PMID- 15246218
TI  - Sporadic cases of acute autochthonous hepatitis E in Spain.
AB  - BACKGROUND/AIMS: In industrialized countries hepatitis E virus (HEV) infection is
      rare and its diagnosis is difficult because the utility of available tests is not
      well established. METHODS: We studied the presence of acute HEV infection markers
      in a cluster of 11 cases of acute hepatitis with IgG anti-HEV antibodies.
      RESULTS: Three cases were confirmed as acute hepatitis E and 8 as presumptive
      hepatitis E, two as a past HEV infection and one could not be determined. Three
      different HEV strains were identified in serum from 3 patients. Two strains
      belonged to genotype 3, the predominant genotype found in local urban sewage and
      the other strain belonged to genotype 1 and was considered an imported strain.
      CONCLUSIONS: Our findings demonstrate the presence of some autochthonous,
      sporadic acute hepatitis E cases as well as an imported case in our area and the
      transitory nature of virological and serological markers for HEV.

PMID- 15246219
TI  - Insulin resistance and insulin secretion in chronic hepatitis C virus infection.
AB  - BACKGROUND/AIMS: Diabetes mellitus (DM) is frequently observed in patients with
      chronic hepatitis caused by hepatitis C virus infection (CHC). The present study
      was designed to determine the pathogenic factors responsible for glucose
      intolerance in CHC patients. METHODS: A total of 131 patients with CHC were
      enrolled in this study. Insulin resistance and beta-cell function were determined
      after 75 g oral glucose tolerance tests. RESULTS: Glucose intolerance was
      detected in 27.5% (36/131) of CHC patients; 10 had DM and 26 impaired glucose
      tolerance. HOMA-R [insulin 0xglucose 0/22.5] was greater in patients with both
      impaired glucose tolerance and DM than in those with normal glucose tolerance
      (P<0.01). Matsuda index [10(4)/ (square root) (mean insulinxmean glucosexglucose
      0xinsulin 0)] was lower in diabetic patients than in those with normal glucose
      tolerance (P<0.05). The insulinogenic index [Deltainsulin 30-0/Deltaglucose 30-0]
      and DeltaC-peptide 30 [DeltaC-peptide 30-0/Deltaglucose 30-0] were significantly
      lower even in patients with impaired glucose tolerance than in patients with
      normal glucose tolerance (P<0.01). CONCLUSIONS: Both insulin resistance and beta
      cell dysfunction contribute to glucose intolerance in CHC patients.

PMID- 15246220
TI  - Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific
      region.
AB  - BACKGROUND/AIMS: The world-wide distribution of hepatitis B virus (HBV) genotypes
      follows a geographic pattern under the influence of ethnic background. METHODS:
      Forty eight core genes from four pacific islands were compared with the following
      findings. RESULTS: First, island-specific variant substitutions were found for
      only two out of four islands. Second, 11 amino acid and 90 nucleotide changes
      specific for pacific genotypes C and D were defined. Third, the nucleotide
      diversity of genotype C (all but one were silent) was greater than that of
      genotype D. CONCLUSIONS: These results suggest an early appearance of genotype C
      in the pacific with few subsequent amino acid changes because of shared
      immunological responses across the region followed by random silent changes, some
      of which reflect isolation of individual island populations. Genotype D appeared
      later.

PMID- 15246221
TI  - Protein restriction in hepatic encephalopathy: necessary evil or illogical dogma?

PMID- 15246222
TI  - The future of fatty livers.

PMID- 15246223
TI  - Acute liver failure: avoidance of deleterious cofactors and early specific
      medical therapy for the liver are better than late intensive care for the brain.

PMID- 15246224
TI  - Hepatitis viruses and human immunodeficiency virus co-infection: pathogenesis and
      treatment.

PMID- 15246225
TI  - Spur-cell anaemia in a patient with cirrhosis.

PMID- 15246226
TI  - Gilbert's syndrome complicating long term parental nutrition.

PMID- 15246227
TI  - Chronic inhibition of nitric oxide synthase and increased vascular responsiveness
      to vasopressin: what is the link?

PMID- 15246228
TI  - Serum vascular endothelial growth factor-receptor 1 during liver regeneration.

PMID- 15246229
TI  - Unsatisfactory quality of hepatological information on the internet.

PMID- 15246230
TI  - Intrabiliary metastasis from rectal cancer mimicking peripheral papillary-type
      cholangiocarcinoma.

PMID- 15246231
TI  - Epstein-Barr virus (EBV)-induced liver failure in the absence of extensive liver
      cell necrosis: a case for cytokine-induced liver dysfunction?

PMID- 15246235
TI  - Essential oils: their antibacterial properties and potential applications in
      foods--a review.
AB  - In vitro studies have demonstrated antibacterial activity of essential oils (EOs)
      against Listeria monocytogenes, Salmonella typhimurium, Escherichia coli O157:H7,
      Shigella dysenteria, Bacillus cereus and Staphylococcus aureus at levels between
      0.2 and 10 microl ml(-1). Gram-negative organisms are slightly less susceptible
      than gram-positive bacteria. A number of EO components has been identified as
      effective antibacterials, e.g. carvacrol, thymol, eugenol, perillaldehyde,
      cinnamaldehyde and cinnamic acid, having minimum inhibitory concentrations (MICs)
      of 0.05-5 microl ml(-1) in vitro. A higher concentration is needed to achieve the
      same effect in foods. Studies with fresh meat, meat products, fish, milk, dairy
      products, vegetables, fruit and cooked rice have shown that the concentration
      needed to achieve a significant antibacterial effect is around 0.5-20 microl g(
      1) in foods and about 0.1-10 microl ml(-1) in solutions for washing fruit and
      vegetables. EOs comprise a large number of components and it is likely that their
      mode of action involves several targets in the bacterial cell. The hydrophobicity
      of EOs enables them to partition in the lipids of the cell membrane and
      mitochondria, rendering them permeable and leading to leakage of cell contents.
      Physical conditions that improve the action of EOs are low pH, low temperature
      and low oxygen levels. Synergism has been observed between carvacrol and its
      precursor p-cymene and between cinnamaldehyde and eugenol. Synergy between EO
      components and mild preservation methods has also been observed. Some EO
      components are legally registered flavourings in the EU and the USA. Undesirable
      organoleptic effects can be limited by careful selection of EOs according to the
      type of food.

PMID- 15246236
TI  - Bactericidal activity of wasabi (Wasabia japonica) against Helicobacter pylori.
AB  - In this study, the bactericidal activity of Korean and Japanese wasabi roots,
      stems and leaves against Helicobacter pylori were examined. Allyl isothiocyanate
      (AIT) in roots, stems and leaves of Korean wasabi were 0.75, 0.18 and 0.32 mg/g,
      respectively. AIT in roots, stems and leaves of Japanese wasabi were 1.18, 0.41
      and 0.38 mg/g, respectively. All parts of wasabi showed bactericidal activities
      against H. pylori strain NCTC 11637, YS 27 and YS 50. The leaves of both wasabi
      showed the highest bactericidal activities with the minimum bactericidal
      concentration of 1.05-1.31 mg of dry weight/ml against three strains of H.
      pylori. The roots showed a little lower bactericidal activity with 2.09-4.17 mg
      of dry weight/ml against them. The main component related to antimicrobial
      activity in wasabi is well known to be AIT. In this study, the bactericidal
      activity of leaves was higher than that of roots, although AIT amount of leaves
      was lower than that of roots. These results suggest that certain components
      besides AIT in wasabi are effective in killing H. pylori.

PMID- 15246237
TI  - Characterization of a carotenoid-hyperproducing yeast mutant isolated by low-dose
      gamma irradiation.
AB  - To isolate a carotenoid-hyperproducing yeast, Phaffia rhodozyma was treated by
      low-dose gamma irradiation below 10 kGy. Through repeated rounds of gamma
      irradiation and visual screening, a mutant 3A4-8 was isolated. It produced 3.3 mg
      of carotenoid per gram of yeast, 50% higher carotenoid content than that of the
      unirradiated strain. Glucose and peptone were the most suitable carbon and
      nitrogen sources for production of carotenoid based on the growth experiment of
      the mutant under various carbon and nitrogen sources. This result suggests that
      low-dose gamma irradiation could be used as a means of mutagenesis for isolation
      of a carotenoid-hyperproducing strain of P. rhodozyma because only the carotenoid
      hyperproducing yeast survives gamma irradiation by scavenging oxygen radicals
      generated by radiolysis of water.

PMID- 15246238
TI  - Isolation, identification and characterisation of the dominant microorganisms of
      kule naoto: the Maasai traditional fermented milk in Kenya.
AB  - From 22 samples of kule naoto, the traditional fermented milk products of the
      Maasai in Kenya, 300 lactic acid bacterial strains were isolated and
      phenotypically characterised by their ability to ferment different carbohydrates
      and by additional biochemical tests. Lactic acid bacteria (LAB), especially the
      genus Lactobacillus, followed by Enterococcus, Lactococcus and Leuconostoc,
      dominated the microflora of these samples. The major Lactobacillus species was
      Lactobacillus plantarum (60%), with a lower frequency of isolation for
      Lactobacillus fermentum, Lactobacillus paracasei and Lactobacillus acidophilus.
      Most strains produced enzymes such as beta-galactosidase and peptidases, which
      are of relevance to cultured dairy product processing, and exhibited similar
      patterns of enzymatic activity between species. Enterobacteriaceae could not be
      detected in 15 out of 22 samples (detection level 10(2)/ml). Conversely, yeasts
      (detection level 10(1)/ml) were detected in those samples in which
      Enterobacteriaceae were not found. The pH values of all these samples were < 4.5.

PMID- 15246239
TI  - Genetic procedures for identification of enterotoxigenic strains of
      Staphylococcus aureus from three food poisoning outbreaks.
AB  - Three food poisoning restaurant outbreaks due to Staphylococcus aureus, occurring
      during June-October 2002 in the Principality of Asturias (PA), Spain, provided
      the basis for investigating some aspects of the molecular epidemiology of this
      organism. The methods applied to identify strains and lineages included multiplex
      polymerase chain reaction (PCR) to detect nine enterotoxin (se) genes, and three
      DNA fingerprinting procedures: pulsed-field gel electrophoresis (PFGE) with SmaI,
      randomly amplified polymorphic DNA (RAPD) with two selected primers, and plasmid
      restriction analysis with HindIII. Thirty-two isolates were differentiated into
      three non-se and 12 se strains, which were outbreak-specific, except for one that
      was represented in two of the outbreaks. In outbreak 1, the 16 food isolates
      analyzed had sec, seg and sei genes and generated a distinctive DNA fingerprint,
      being assigned to a single strain. This strain could be categorized as endemic in
      the PA and associated to manually handled dairy products and nasal carriers. In
      outbreak 2, the four food isolates analyzed fell into three strains, each one
      displaying a different se-gene profile (sea, sec and seg-seh-sei) and a
      distinctive DNA fingerprint. In outbreak 3, the five food isolates tested fell
      into four seg-sei strains generating identical RAPD but different PFGE and
      plasmid profiles, and one sea strain also collected from two nasal carriers. This
      last strain had also been found in manually handled vegetables in outbreak 2, and
      it belongs to a not very frequently found sea lineage in the PA. Multiplex-PCR to
      detect se genes together with the three applied DNA fingerprint typing procedures
      proved therefore to be useful tools in subclassifying S. aureus for
      epidemiological purposes.

PMID- 15246240
TI  - Phenotypic and PCR-based characterization of the microflora in Norvegia cheese
      during ripening.
AB  - Microbiological sampling of Norvegia cheese from three cheese factories was done
      during ripening. The evolution of aerobic mesophilic bacteria, lactococci,
      lactobacilli, enterococci, presumptive leuconostoc and pediococci was
      investigated after 30, 90, 180 and 270 days of ripening. Isolates (135) of non
      starter lactic acid bacteria (NSLAB) from nine Norvegia cheeses after 90, 180 and
      270 days of ripening were examined. The isolates were tested by physiological and
      biochemical assays, species-specific PCR and 16S rDNA sequencing. After 90 days
      of ripening Leuconostoc spp., most probably from the starter, and the NSLAB
      specie Lactobacillus paracasei dominated among the isolates, however, after
      longer ripening Lb. paracasei dominated. The development and evolution of the
      microflora in Norvegia varied according to dairy and ripening time.

PMID- 15246241
TI  - Occurrence and significance of Bacillus thuringiensis on wine grapes.
AB  - Wine grapes harvested at different stages during cultivation from several
      vineyards in New South Wales, Australia, harboured Bacillus thuringiensis at
      viable populations of 10(2)-10(6) cfu/g. Commercial preparations of B.
      thuringiensis had been sprayed onto the grapes as a biological insecticide. B.
      thuringiensis (10(1)-10(3) cfu/ml) was isolated from grape juice and fermenting
      grape juice in a commercial winery. Although B. thuringiensis remained viable
      when inoculated at 10(3)-10(4) cfu/ml into grape juice and wine (pH 3.0-6.0), it
      did not grow. Using in vitro agar culture assays, B. thuringiensis inhibited
      several grape-associated yeasts and bacteria as well as various species of fungi
      associated with grape spoilage and ochratoxin A production. B. thuringiensis did
      not inhibit Saccharomyces cerevisiae in agar culture or during alcoholic
      fermentation of grape juice. B. thuringiensis inhibited the malolactic bacterium,
      Oenococcus oeni, in agar culture but not during mixed cultures in a liquid
      medium.

PMID- 15246242
TI  - Effects of mastic resin and its essential oil on the growth of proteolytic
      Clostridium botulinum.
AB  - Studies were done to determine the effect of mastic resin and its essential oil,
      alone and in conjunction with ethanol, on the growth of proteolytic strains of
      Clostridium botulinum in media, and on neurotoxin production in challenge studies
      with English-style crumpets. Preliminary studies, using a spot-on-the-lawn
      method, indicated that high levels of mastic resin in ethanol ( approximately 8%
      w/w) were required for complete inhibition of all strains of C. botulinum tested,
      but mastic resin in ethanol had a greater anti-botulinal effect than ethanol
      alone. However, only low levels of mastic oil ( approximately 0.3% v/v) were
      required for inhibition of proteolytic strains of C. botulinum. Both studies
      showed a strain specific inhibition, with C. botulinum type A strains being more
      sensitive to mastic resin and its essential oil than type B strains. However,
      mastic resin in ethanol proved to be more effective when used as a vapor phase
      inhibitor applied to cotton pads and placed inside inoculated plates than when
      added directly to media. While both mastic resin and its essential oil inhibited
      the growth of proteolytic strains of C. botulinum in vitro, they failed to
      inhibit neurotoxin production in challenge studies with C. botulinum in English
      style crumpets.

PMID- 15246243
TI  - Listeria monocytogenes isolated from cold-smoked fish products in Osaka City,
      Japan.
AB  - Listeria monocytogenes contamination of ready-to-eat seafood products
      commercially available in Osaka was examined between 1999 and 2000. L.
      monocytogenes was isolated from 12 (13%) of the 95 products tested. All positive
      samples were from cold-smoked fish with 9 being obtained during the summer.
      Thirteen isolates of L. monocytogenes were typed by pulsed-field gel
      electrophoresis (PFGE) and polymerase chain reaction (PCR)-based typing methods.
      Isolates of the same serotype originating from the same manufacturer gave similar
      DNA profiles, irrespective of the type of sample or date of isolation. The
      finding suggest that persistent strains in each manufacturing facility
      proliferate during the summer and contaminate products during manufacturing
      processes.

PMID- 15246244
TI  - Evaluation of five essential oils from aromatic plants of Cameroon for
      controlling food spoilage and mycotoxin producing fungi.
AB  - Five essential oils (EO) extracted from Cymbopogon citratus, Monodora myristica,
      Ocimum gratissimum, Thymus vulgaris and Zingiber officinale were investigated for
      their inhibitory effect against three food spoilage and mycotoxin producing
      fungi, Fusarium moniliforme, Aspergillus flavus and Aspergillus fumigatus. Five
      strains of each fungus were tested. The agar dilution technique was used to
      determine the inhibitory effect of each EO on the radial growth of the fungus,
      and a dose response was recorded. The EO from O. gratissimum, T. vulgaris and C.
      citratus were the most effective and prevented conidial germination and the
      growth of all three fungi on corn meal agar at 800, 1000 and 1200 ppm,
      respectively. Moderate activity was observed for the EO from Z. officinale
      between 800 and 2500 ppm, while the EO from M. myristica was less inhibitory.
      These effects against food spoilage and mycotoxin producing fungi indicated the
      possible ability of each essential oil as a food preservative. A comparative test
      on the preservative ability of the EO from O. gratissimum and potassium sorbate
      against A. flavus at pH 3.0 and 4.5 showed that the EO remained stable at both
      pH, whereas the efficacy of potassium sorbate was reduced at higher pH. We
      concluded that the EO from O. gratissimum is a potential food preservative with a
      pH dependent superiority against potassium sorbate, and these are novel
      scientific information.

PMID- 15246245
TI  - The use of intravenous immunoglobulin in the treatment of autoimmune
      neuromuscular diseases: evidence-based indications and safety profile.
AB  - Intravenous immunoglobulin (i.v.Ig) has multiple actions on the immunoregulatory
      network that operate in concert with each other. For each autoimmune
      neuromuscular disease, however, there is a predominant mechanism of action that
      relates to the underlying immunopathogenetic cause of the respective disorder.
      The best understood actions of i.v.Ig include the following: (a) modulation of
      pathogenic autoantibodies, an effect relevant in myasthenia gravis (MG), Lambert
      Eaton myasthenic syndrome (LEMS), Guillain-Barre syndrome (GBS), chronic
      inflammatory demyelinating polyneuropathy (CIDP), and stiff-person syndrome
      (SPS); (b) inhibition of complement activation and interception of membranolytic
      attack complex (MAC) formation, an action relevant to the complement-mediated
      mechanisms involved in GBS, CIDP, MG, and dermatomyositis (DM); (c) modulation of
      the inhibitory or activation Fc receptors on macrophages invading targeted
      tissues in nerve and muscle, as seen in CIDP, GBS, and inflammatory myopathies;
      (d) down-regulation of pathogenic cytokines and adhesion molecules; (e)
      suppression of T-cell functions; and (f) interference with antigen recognition.
      Controlled clinical trials have shown that i.v.Ig is effective as first-line
      therapy in patients with GBS, CIDP, and multifocal motor neuropathy (MMN), and as
      second-line therapy in DM, MG, LEMS, and SPS. In paraproteinemic IgM anti-MAG
      (myelin-associated glycoprotein) demyelinating polyneuropathies and inclusion
      body myositis (IBM), the benefit is variable, marginal, and not statistically
      significant. i.v.Ig has a remarkably good safety record for long-term
      administration, however, the following side effects have been observed: mild,
      infusion-rate-related reactions, such as headaches, myalgia, or fever; moderate
      but inconsequential events, such as aseptic meningitis and skin rash; and severe,
      but rare, complications, such as thromboembolic events and renal tubular
      necrosis. Future studies are needed to (a) find the appropriate dose and
      frequency of infusions that maintain a response; (b) address pharmacoeconomics,
      comparing the high cost of i.v.Ig to the cost of the other therapies, which,
      although less expensive, cause significantly more long-term side effects; (c)
      determine why some patients respond better than others; and (d) examine the
      merits of combining i.v.Ig with other immunosuppressive drugs.

PMID- 15246246
TI  - Regulation of GABAA receptor trafficking, channel activity, and functional
      plasticity of inhibitory synapses.
AB  - Neural inhibition in the brain is mainly mediated by ionotropic gamma
      aminobutyric acid type A (GABA(A)) receptors. Different subtypes of these
      receptors, distinguished by their subunit composition, are either concentrated at
      postsynaptic sites where they mediate phasic inhibition or found at perisynaptic
      and extrasynaptic locations where they prolong phasic inhibition and mediate
      tonic inhibition, respectively. Of special interest are mechanisms that modulate
      the stability and function of postsynaptic GABA(A) receptor subtypes and that are
      implicated in functional plasticity of inhibitory transmission in the brain. We
      will summarize recent progress on the classification of synaptic versus
      extrasynaptic receptors, the molecular composition of the postsynaptic
      cytoskeleton, the function of receptor-associated proteins in trafficking of
      GABA(A) receptors to and from synapses, and their role in post-translational
      signaling mechanisms that modulate the stability, density, and function of
      GABA(A) receptors in the postsynaptic membrane.

PMID- 15246247
TI  - Implications of the natriuretic peptide system in the pathogenesis of heart
      failure: diagnostic and therapeutic importance.
AB  - The natriuretic peptide family consists of at least 3 structurally similar
      peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and
      C-type natriuretic peptide (CNP). Under normal conditions, ANP is synthesized by
      the atrium and released in response to atrial stretch. This peptide plays an
      important role in sodium and water homeostasis and is involved in cardiovascular
      function. In contrast, BNP is synthesized primarily by the ventricles, and its
      circulatory concentrations are significantly elevated in profound congestive
      heart failure (CHF). While both plasma levels of ANP and BNP have been found to
      be increased in patients with various heart diseases, the elevation in
      circulatory BNP correlates better than ANP with the severity of CHF. Therefore,
      plasma BNP has been suggested (and lately used) to aid in the accurate diagnosis
      of heart failure in patients admitted to the emergency room with symptoms of
      decompensated heart failure. Furthermore, circulatory BNP has been utilized as a
      prognostic marker in CHF as well as a hormone guide in the evaluation of the
      efficacy of the conventional treatment of this disease state. In light of the
      cardiovascular and renal effects of BNP, which most likely exceed those of ANP,
      the former has been used as a therapeutic agent for the treatment of patients
      with acute severe CHF. Intravenous infusion of BNP into patients with sustained
      ventricular dysfunction causes a balanced arterial and venous vasodilatation that
      has been shown to result in rapid reduction in ventricular filling pressure and
      reversal of heart failure symptoms, such as dyspnea and acute hemodynamic
      abnormalities. Thus, the goal of this article is to review the physiology and
      pathophysiology of natriuretic peptides and the potential use of their
      circulating levels for diagnosis and treatment of heart failure.

PMID- 15246248
TI  - A glance at G-protein-coupled receptors for lipid mediators: a growing receptor
      family with remarkably diverse ligands.
AB  - A plethora of lipid-like molecules known to act as intracellular second
      messengers are now recognized to signal cells through plasma membrane 7
      transmembrane G-protein-coupled receptors (GPCRs). This has been the result of a
      decade-long genetic hunt for novel sequences encoding 7 transmembrane receptor
      proteins and the efforts to pair novel sequences with biologically active
      substances of (partly) unknown molecular mechanism of action. Identification of
      novel GPCR ligand pairs represents the first step to shed more light into the
      mode of action of novel cellular signaling molecules in human health and disease
      and might represent a fruitful source for the development of new drugs, judged on
      the successful history of GPCR as drug targets. Since 2000, more than 16 reports
      became available on lipid mediators--as diverse as lysophospholipids, arachidonic
      acid metabolites, short-, medium-, and long-chain fatty acids as well as steroid
      like molecules--exerting their effects as extracellular mediators via rhodopsin
      like family GPCRs. These reports have opened new avenues for research in human
      lipid receptor physiology and pharmacology. Here, the current knowledge on the
      recently deorphanized lipid receptors, including their isolation, expression
      pattern, function, and possible physiological or pathological roles will be
      reviewed.

PMID- 15246249
TI  - Interactions between NK cells and B lymphocytes.

PMID- 15246250
TI  - Multitasking of helix-loop-helix proteins in lymphopoiesis.

PMID- 15246251
TI  - Customized antigens for desensitizing allergic patients.

PMID- 15246252
TI  - Immune response against dying tumor cells.

PMID- 15246253
TI  - HMGB1 in the immunology of sepsis (not septic shock) and arthritis.

PMID- 15246254
TI  - Selection of the T-cell repertoire: receptor-controlled checkpoints in T-cell
      development.

PMID- 15246255
TI  - The pathogenesis of diabetes in the NOD mouse.

PMID- 15246256
TI  - Feline immunodeficiency virus Orf-A localizes to the nucleus and induces cell
      cycle arrest.
AB  - Feline immunodeficiency virus (FIV) gene orf-A, also designated orf-2, encodes a
      77 amino acid accessory protein reported to be critical for efficient viral
      replication in vitro and in vivo and previously implicated to encode a Tat
      protein for FIV. However, recent studies have shown Orf-A to be important in the
      late steps of the FIV life cycle involved in virion formation and in early steps
      involved in virus infectivity. The present study reports that expression of a GFP
      Orf-A fusion protein in both primate and feline cell lines results in nuclear
      localization of this FIV accessory protein. Moreover, a nuclear localization
      signal (NLS) critical for nuclear import was mapped to amino acid residues 43
      through 53 of Orf-A. Lastly, transient expression of GFP-Orf-A in cells induced
      an arrest at the second gap (G(2)) of the cell cycle. Our findings reveal that
      Orf-A is a nuclear protein that expresses properties similar to those reported
      for human immunodeficiency virus-1 (HIV-1)-encoded Vpr.

PMID- 15246257
TI  - Culturing of HIV-1-specific cytotoxic T lymphocytes with interleukin-7 and
      interleukin-15.
AB  - The ability to study HIV-1-specific cytotoxic T cell (CTL) clones in models in
      vitro or to expand them for immunotherapeutic use is limited by the technical
      difficulty of propagating these cells. The factors that determine the survival
      and proliferation of the cells are incompletely understood and could include
      cytokines provided from feeder cells or serum. We therefore investigated the
      effects of adding two cytokines reported to have effects on T cell proliferation
      and function, interleukin (IL)-7 and IL-15. Four HIV-1-specific clones derived
      from infected persons were cultured under standard conditions with IL-2 compared
      to IL-7 or IL-15 alone or in combination with IL-2. Proliferation and survival,
      as reflected by cell numbers after stimulation, were poorly supported by IL-7 or
      IL-15 alone, and these cytokines appeared to provide no additional benefit when
      added to IL-2. Similarly, these cytokines alone did not support the functional
      status of these cells as measured by chromium release assays with peptide-pulsed
      target cells. Addition of IL-7 or IL-15 to IL-2 did not augment function of the
      cells. These data suggest that supplementing CTL cultures with these cytokines
      does not provide improvement of cell growth or function.

PMID- 15246258
TI  - Distinct patterns of natural selection in the reverse transcriptase gene of HIV-1
      in the presence and absence of antiretroviral therapy.
AB  - The emergence of human immunodeficiency virus (HIV) drug-resistant mutations
      during antiretroviral therapy is explained by either the preexistence of low
      frequency-resistant strains before the start of therapy or by the selection of
      unsuppressed resistant strains during therapy. We used pairwise and maximum
      likelihood analyses of the ratio of nonsynonymous to synonymous substitutions per
      site (d(N)/d(S)) to study the extent of positive selection in the reverse
      transcriptase (RT) gene of HIV-1 from multiple data sets of drug-treated (117
      sequences) and drug-naive patients (270 sequences). In the pairwise analysis,
      evidence for positive selection (d(N)/d(S) > 1) was only found in drug-treated
      individuals and in codons conferring drug resistance. By the maximum likelihood
      method, a positive selection at codons conferring drug resistance was only
      observed in patients receiving therapy, and although positive selection was
      detected in drug-naive patients, this was always at codons unrelated to drug
      resistance. We therefore document a striking difference in the process of allele
      fixation in drug resistance codons (RC) between populations of HIV-1-infected
      individuals naive to treatment and those receiving therapy. Furthermore, although
      mutations associated with drug resistance are sometimes found in drug-naive
      patients, we suggest that these are fixed because of linkage to sites
      experiencing immune escape. Finally, we show that compensatory changes are likely
      to be important in the development of HIV drug resistance by counter-acting the
      deleterious effects normally associated with drug resistance mutations.

PMID- 15246259
TI  - Mucosal immunization with attenuated Shigella flexneri harboring an influenza
      hemagglutinin DNA vaccine protects mice against a lethal influenza challenge.
AB  - Mucosal surfaces are important for the induction of immunity against influenza
      virus. In a murine intranasal immunization model, we demonstrated that the
      attenuated Shigella flexneri Deltaasd strain 15D, carrying a DNA construct
      encoding the influenza virus hemagglutinin (HA), induces protective immunity
      against a lethal respiratory challenge with influenza A/WSN/33. Influenza virus
      specific IFN-gamma T cells were detected among splenocytes, and anti-HA IgG was
      detected in serum post-immunization, albeit at low levels. Following influenza
      virus challenge, an accelerated anti-HA IgA antibody response was detected in
      bronchoalveolar lavage (BAL) washings from mice vaccinated with attenuated
      shigella containing the HA construct. These results suggest that S. flexneri
      Deltaasd strain 15D is a promising vector for mucosal DNA vaccine immunization
      against influenza virus and other mucosal pathogens.

PMID- 15246260
TI  - Semliki Forest virus produced in the absence of the 6K protein has an altered
      spike structure as revealed by decreased membrane fusion capacity.
AB  - We examined the kinetics of membrane fusion of wild type (wt) and Delta6K mutant
      Semliki Forest virus in a liposomal model system. The final extent of membrane
      fusion of the mutant (at pH 5.5) was approximately one third that of the wt
      virus, although the level of E1 (fusion protein) trimerization was, in fact,
      greater than that of the wt. Studies on the effect of exposure of the viruses to
      low pH revealed that the Delta6K mutant was inactivated much more rapidly than
      the wt virus. It is this instability of the mutant particles which probably
      accounts for the lower fusion levels. Moreover, fusion of the Delta6K mutant was
      significantly increased by the inclusion of lipid-conjugated heparin in the
      target liposomes. We conclude that the presence of the 6K protein either in the
      particle or during the assembly process is important for the correct assembly of
      the fully infectious SFV particle.

PMID- 15246261
TI  - Electron microscopy of an alpha-dystroglycan fragment containing receptor sites
      for lymphocytic choriomeningitis virus and laminin, and use of the receptoid body
      as a reagent to neutralize virus.
AB  - We report the electron microscopic structure of an alpha-dystroglycan (alpha-DG)
      fragment (DGEKFc4) that contains binding sites for lymphocytic choriomeningitis
      virus (LCMV) and the extracellular matrix (ECM) molecule laminin. In electron
      microscopic images, DGEKFc4 appears as dumbbell-shaped rods with a length of 7.5
      +/- 0.5 nM and width of 3 +/- 0.3 nM. The C-terminal human Fc allows binding of
      anti-human Fc antibody resulting in formation of immune complexes that preserve
      alpha-DG binding to virus. Electron microscopy shows the antibody binding to near
      one end of the dumbbell-shaped rods. Because arenaviruses like LCMV or Lassa
      fever virus (LFV) generate poor neutralizing antibodies during natural infection
      or vaccination, we assayed whether the alpha-DG receptoid bodies generated could
      be used as an efficient antibody mimic. However, the receptor body formed by
      either alpha-DG fragment alone or complexed to antibody to human Fc failed to
      efficiently neutralize virus.

PMID- 15246262
TI  - Mapping the phosphoprotein binding site on Sendai virus NP protein assembled into
      nucleocapsids.
AB  - To catalyze RNA synthesis, the Sendai virus P-L RNA polymerase complex first
      binds the viral nucleocapsid (NC) template through an interaction of the P
      subunit with NP assembled with the genome RNA. For replication, the polymerase
      utilizes an NP(0)-P complex as the substrate for the encapsidation of newly
      synthesized RNA which involves both NP-RNA and NP-NP interactions. Previous
      studies showed that the C-terminal 124 amino acids of NP (aa 401-524) contain the
      P-NC binding site. To further delineate the amino acids important for this
      interaction, C-terminal truncations and site-directed mutations in NP were
      characterized for their replication activity and protein-protein interactions.
      This C-terminal region was found in fact to be necessary for several different
      protein interactions. The C-terminal 492-524 aa were nonessential for the
      complete activity of the protein. Deletion of amino acids 472-491, however,
      abolished replication activity due to a specific defect in the formation of the
      NP(0)-P complex. Binding of the P protein of the polymerase complex to NC
      required aa 462-471 of NP, while self-assembly of NP into NC required aa 440-461.
      Site-directed mutations from aa 435 to 491 showed, however, that the charged
      amino acids in this region were not essential for these defects.

PMID- 15246263
TI  - Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated
      herpesvirus lytic gene expression.
AB  - A hallmark of all herpesvirus is the ability to exist in either a latent, or
      lytic, state of replication, enabling the lifelong infection of its host.
      Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) can efficiently establish a
      latent infection in a variety of cell types in vitro, making it a valuable model
      for the study of latency and reactivation. To facilitate the identification of
      KSHV lytic replication, and allow subsequent experiments with live cells, a
      recombinant virus, rKSHV.219, was constructed using JSC-1 cells that expresses
      the red fluorescent protein (RFP) from the KSHV lytic PAN promoter, the green
      fluorescent protein (GFP) from the EF-1alpha promoter, and with the gene for
      puromycin resistance as a selectable marker. rKSHV.219 from JSC-1 cells was used
      to infect Vero cells for purification of the recombinant virus. Vero cells were
      also used for the production of rKSHV.219 at levels of 10(5)-10(6) infectious
      units (IU) of virus per milliliter using a combination of KSHV/RTA expressed from
      a baculovirus vector, BacK50, and butyrate. Virus produced from Vero cells was
      used to infect human fibroblasts (HF), 293, DU145, T24, HaCaT, and HEp-2 cells,
      and in all cells except 293 cells, only a latent infection was established with
      GFP expression, but no RFP expression. In 293 cells, 10-15% of cells showed lytic
      gene expression. Both primary and immortalized microvascular endothelial cells
      (MVEC) were also infected with rKSHV.219, and reduced spontaneous lytic
      replication was found in immortalized cells. In all cells used in this study,
      rKSHV.219 efficiently established latent infections from which the virus could be
      reactivated to productive lytic replication. This work also demonstrated strong
      synergy between KSHV/RTA and butyrate for the activation of KSHV lytic
      replication and the production of infectious virus.

PMID- 15246264
TI  - Similar activation of signal transduction pathways by the herpesvirus-encoded
      chemokine receptors US28 and ORF74.
AB  - The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74
      from human herpesvirus 8 are both constitutively active. We show that both
      receptors constitutively activate the transcription factors nuclear factor of
      activated T cells (NFAT) and cAMP response element binding protein (CREB) and
      that both pathways are modulated by their respective endogenous receptor ligands.
      By addition of specific pathway modulators against the G protein subunit Galphai,
      phospholipase C, protein kinase C, calcineurin, p38 MAP kinase, and MEK1, we find
      that the constitutive and ligand-dependent inductions are mediated by multiple
      yet similar pathways in both receptors. The NFAT and CREB transcription factors
      and their upstream activators are known inducers of host and virally encoded
      genes. We propose that the activity of these virally encoded chemokine receptors
      coordinates host and potentially viral gene expression similarly. As ORF74 is a
      known inducer of neoplasia, these findings may have important implications for
      cytomegalovirus-associated pathogenicity.

PMID- 15246265
TI  - Inducible-costimulator-mediated suppression of human immunodeficiency virus type
      1 replication in CD4(+) T lymphocytes.
AB  - We investigated the effects of signaling through CD28 family molecules on human
      immunodeficiency virus type 1 (HIV-1) replication in vitro. A monoclonal antibody
      (mAb) specific for inducible costimulator (ICOS) suppressed both X4 and R5 HIV-1
      replication in CD4(+) peripheral blood mononuclear cells (PBMC). This suppression
      was not attributable to reduced cell growth or viability. CD28 mAb showed
      variable effects and also suppressed HIV-1 replication when immobilized.
      Replication of pseudotype viruses with HIV-1-but not with vesicular stomatitis
      virus G-envelope was efficiently suppressed in CD4(+) PBMC treated with ICOS or
      CD28 mAbs. However, CD4, CXCR4, and CCR5 expression on the surface was not down
      regulated. Moreover, HIV-1 replication in CD4(+) PBMC was suppressed by a soluble
      form of human B7-H2, a ligand of ICOS, but was enhanced by soluble B7-1, a ligand
      for CD28. These findings suggest that natural or artificial ligands for ICOS
      potentially suppress HIV-1 replication mainly at the entry stages.

PMID- 15246266
TI  - Evidence that the human cytomegalovirus 46-kDa UL72 protein is not an active
      dUTPase but a late protein dispensable for replication in fibroblasts.
AB  - The Human Cytomegalovirus (HCMV) UL72 gene is considered to be the equivalent of
      the dUTPase gene of the Alpha- and Gamma-herpesviruses. To characterize its
      function, the expression profiles of UL72 at both the RNA and the protein level
      were determined. The gene is expressed with a late kinetics and the corresponding
      UL72 46-kDa protein accumulates late during infection in the cytoplasm of
      infected cells. The pUL72 was expressed in E. coli and the purified recombinant
      protein did not display a detectable dUTPase activity. The viral yields of
      reconstituted HCMV RVDeltaUL72 viruses carrying a deletion within the UL72 ORF
      demonstrated a moderate growth defect following low MOI infections, whereas their
      DNA synthesis profiles were not significantly different from those of the
      parental HCMV RVAD169. These results demonstrate that the UL72 gene product is
      not a dUTPase and is not essential for replication in human fibroblasts.

PMID- 15246267
TI  - The DNA form of a retroviroid-like element is involved in recombination events
      with itself and with the plant genome.
AB  - Carnation small viroid-like RNA (CarSV RNA) is unique among plant viroid-like
      RNAs in having a homologous DNA counterpart. In the present study, we found the
      most abundant CarSV DNA form (275 nt) coexisting with other smaller and longer
      than-unit forms. Further analysis of PCR-amplified products revealed the presence
      of CarSV DNA-related sequences integrated in the plant genome, fused to
      microsatellite-like genomic sequences. Six to seven nucleotides at the boundaries
      in the CarSV DNA sequence could be found in the genomic sequences and also
      delimiting the boundaries of an enlarged version with partial duplication. This
      suggests that a common mechanism might have played a role in their emergence,
      namely, polymerase pausing and switching between stretches of homologous
      sequences. These plants also contained deleted CarSV DNA mutants with boundaries
      near those observed with fused sequences.

PMID- 15246268
TI  - H1 and H7 influenza haemagglutinin structures extend a structural classification
      of haemagglutinin subtypes.
AB  - Comparing the structures of H3, H5 and H9 subtype haemagglutinins, we deduced a
      structural basis for including all 15 influenza subtypes in four clades. H3, H5
      and H9 represent three of these clades; we now report the structure of an H7 HA
      as a representative of the fourth clade. We confirm the structure of the turn at
      the N-terminus of the conserved central alpha-helix of HA2, and the combination
      of ionisable residues near the "fusion peptide" as clade-specific features. We
      compare the structures of three H1 HAs with H5 HA in the same clade, to refine
      our previous classification and we confirm the division of the clades into two
      groups of two. We also show the roles of carbohydrate side chains in the esterase
      fusion domain boundaries in the formation of clade-specific structural markers.

PMID- 15246269
TI  - A single amino acid change in gp41 is linked to the macrophage-only replication
      phenotype of a molecular clone of simian immunodeficiency virus derived from the
      brain of a macaque with neuropathogenic infection.
AB  - Simian immunodeficiency virus (SIV)-related neuropathogenesis has been observed
      in 90% of pig-tailed macaques infected with strain SIVsmmFGb, making it an
      excellent system for studying human immunodeficiency virus (HIV)-associated
      neurological disease. To investigate the genetics of SIV neurovirulence,
      infectious molecular clones were generated from the brain of a SIVsmmFGb-infected
      pig-tailed macaque. One clone, BPZm.12, displayed a macrophage-restricted
      phenotype not previously described; this clone replicated to high levels in
      macrophages, but did not replicate in peripheral blood mononuclear cells (PBMC)
      until at least 21 days postinfection. Sequence analysis of the env gene of
      BPZm.12 revealed the substitution of a serine residue for a highly conserved
      proline residue at position 629 in gp41. A mutant clone, which contained the
      conserved proline to serine (BPZm.12-629P), was able to replicate in both
      macrophages and PBMC without delay. A mutant of an unrelated dual tropic
      molecular clone PBj6.6, substituting proline for serine (PBj6.6-629S), replicated
      to high levels in macrophages, but did not replicate in PBMC at any time point.
      These data indicated that a single determinant in gp41 of an SIV clone changed
      its phenotype from macrophage tropic to dual tropic.

PMID- 15246271
TI  - In vitro papillomavirus capsid assembly analyzed by light scattering.
AB  - Pentamers of the L1 major capsid protein of human papillomavirus (HPV type 11)
      were purified after expression in E. coli and analyzed for the kinetics of in
      vitro capsid self-assembly using multi-angle light scattering (MALS). Pentamers
      self-assembled into capsid-like structures at a rate that was a function of
      protein concentration. The kinetics of capsid formation were sigmoidal with a
      concentration-dependent lag phase, followed by a rapid increase in
      polymerization. Nucleation size and the rate order of subsequent subunit addition
      were calculated from the concentration dependence of the extent of capsid
      formation and the rate of the fast phase, respectively. Assembly was second order
      with a nucleation size of two pentamers. Thus, we suggest that dimers of
      pentamers are the nucleus for L1 assembly into capsid-like structures, with rapid
      sequential addition of single pentamers to the growing shell. Although studied in
      vitro without accessory factors that may be present in vivo, these data are in
      contrast with the "five-around-one" assembly nucleus previously proposed for
      polyomaviruses.

PMID- 15246270
TI  - A highly pathogenic porcine reproductive and respiratory syndrome virus generated
      from an infectious cDNA clone retains the in vivo virulence and transmissibility
      properties of the parental virus.
AB  - The nucleotide sequence of a highly pathogenic porcine reproductive and
      respiratory syndrome virus (PRRSV) was determined. Transfection of MARC-145 cells
      with capped in vitro transcripts derived from a full-length cDNA clone of the
      viral genome resulted in infectious PRRSV with growth characteristics similar to
      that of the parental virus. Primer extension analysis revealed that during
      replication, the viral polymerase corrected the two nonviral guanosine residues
      present at the 5' terminus of the transfected transcripts. Animal studies showed
      that the cloned virus induced hyperthermia, persistent viremia, and antibody
      response, similar to that observed with the parental virus. Contact transmission
      occurred rapidly within 3 days of introduction of naive pigs into the group of
      clone virus-inoculated pigs. These results suggest that the cloned virus retains
      the in vivo virulence and contagion properties of the parental virus, thus,
      providing the background for reverse genetics manipulation in systematic
      examination of attenuation and virulence phenotypes.

PMID- 15246272
TI  - Low-level HIV replication in mixed glial cultures is associated with alterations
      in the processing of p55(Gag).
AB  - We report a novel long-lived infection model in human mixed glial cultures
      (microglia) whereby cells harbor replication-competent HIV-1 for up to 2.5 months
      after infection; a model that potentially mimics latency within the central
      nervous system (CNS). Infection of mixed glial cultures in the presence of serum,
      cytokines, and growth factors (activating conditions) resulted in a robust
      productive infection of microglial cells as previously described for purified
      microglia. In contrast, similar mixed glial cells cultured in serum-free medium
      without cytokines or growth factors (mirroring a nonactivated CNS) supported HIV
      1 entry, reverse transcription, integration, and transcription, yet released
      little or no infectious virus. We found instead that nonactivated mixed glial
      cells expressed almost 10-fold less Gag protein, but more importantly, analysis
      of the intracellular Gag products in quiescent cells showed an aberrant p55/p24
      Gag processing phenotype that appeared to be due to the premature activity of the
      viral protease. These results suggest that the cellular environment in
      nonactivated microglia cells in these mixed glial cultures is not conducive to
      proper Gag processing and virus release. This long-lived infection model will be
      useful in identifying factors that are key for viral maturation in cells of the
      macrophage lineage.

PMID- 15246273
TI  - Binding of influenza viruses to sialic acids: reassortant viruses with A/NWS/33
      hemagglutinin bind to alpha2,8-linked sialic acid.
AB  - We have examined the specificity of binding of A/NWS/33 hemagglutinin (HA),
      exploring the effects of fucosylation, changing the Gal-GlcNAc linkage between
      the second and third sugars, and binding affinity for alpha2,8-linked sialic
      acid. The HA of A/NWS/33(HA)-Tokyo/67(NA) (NWS-Tok, H1N2) virus binds to 3'
      linked sialyllactose with 10-fold higher affinity than 3' sialyllactosamine and 3
      fold higher affinity than 6' sialyllactosamine. The P227H mutation in
      A/NWS/33(P227H)(HA)-A/Memphis/31/98(NA) (NWS-Mem/98, H1N2) results in sevenfold
      lower affinity for 3' sialyllactose, but binding to 6' sialyllactosamine is
      unchanged. The apparent switch from 3' to 6' specificity is solely due to a loss
      of Siaalpha2,3 binding. Fucosylation of the third sugar and changing the linkage
      between second and third sugars had little effect on binding by NWS-Tok, but
      marked effects on A/NWS/33(P227H)(HA)-tern/Australia/G70c/75(NA) (NWS-G70c, H1N9)
      and NWS-Mem/98. NWS-Tok, NWS-G70c, and NWS-Mem/98 bind to alpha2,8-bisialic acid
      with high affinity. NWS-Mem/98 can also bind to alpha2,8-trisialic acid, but with
      lower affinity. Together, these data show that alpha2,8-linked sialic acid,
      fucosylation of the third sugar, and linkage between the second and third sugars
      could play important roles in allowing efficient virus binding to its host cell.
      The finding that influenza viruses have the potential to bind to alpha2,8-linked
      sialic acid is a new influenza virus-receptor interaction pathway.

PMID- 15246274
TI  - Complete genomic DNA sequence of rock bream iridovirus.
AB  - Iridovirus is a causative agent of epizootics among cultured rock bream
      (Oplegnathus fasciatus) in Korea. Here, we report the complete genomic sequence
      of rock bream iridovirus (RBIV). The genome of RBIV was 112080 bp long and
      contained at least 118 putative open reading frames (ORFs), and its genome
      organization was similar to that of infectious spleen and kidney necrosis virus
      (ISKNV). Of the RBIV's 118 ORFs, 85 ORFs showed 60-99% amino acid identity to
      those of ISKNV. Phylogenetic analysis of major capsid protein (MCP), DNA repair
      protein RAD2, and DNA polymerase type-B family indicated that RBIV is closely
      related to red sea bream iridovirus (RSIV), Grouper sleepy disease iridovirus
      (GSDIV), Dwarf gourami iridovirus (DGIV), and ISKNV. The genome sequence provides
      useful information concerning the evolution and divergence of iridoviruses in
      cultured fish.

PMID- 15246275
TI  - A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus
      interacts with RNA-binding protein PCBP1 and controls gene expression through the
      IRES.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8,
      HHV-8) belongs to the gamma-herpesvirus subfamily. The KSHV ORF57 gene is thought
      to be a homolog of posttranscriptional regulators that are conserved in the
      herpesvirus family and are essential for replication. We generated specific
      monoclonal antibodies (mAbs) against the ORF57 protein that detected the 51-kDa
      protein expressed in the nucleus of KSHV-infected cells. We also found that the
      ORF57 protein interacted with poly(rC)-binding protein 1 (PCBP1), a cellular RNA
      binding, posttranscriptional regulator. ORF57's interaction with PCBP1 enhanced
      the activity of not only poliovirus internal ribosome-entry site (IRES)-dependent
      translation but also X-linked inhibitor of apoptosis (XIAP) and KSHV vFLIP IRES.
      Actually, when ORF57 expression was induced by the expression of replication and
      transcription activator (RTA) in KSHV-infected cells, the expression of XIAP was
      enhanced. These results suggest that ORF57 binds to PCBP1 as a functional partner
      for posttranscriptional regulation and is involved in the regulation of the
      expression of both cellular and viral genes through IRESs.

PMID- 15246276
TI  - Accumulation of maize chlorotic dwarf virus proteins in its plant host and
      leafhopper vector.
AB  - The genome of Maize chlorotic dwarf virus (MCDV; genus Waikavirus; family
      Sequiviridae) consists of a monopartite positive-sense RNA genome encoding a
      single large polyprotein. Antibodies were produced to His-fusions of three
      undefined regions of the MCDV polyprotein: the N-terminus of the polyprotein
      (R78), a region between coat proteins (CPs) and the nucleotide-binding site (NBS)
      (R37), and a region between the NBS and a 3C-like protease (R69). The R78
      antibodies react with proteins of 50 kDa (P50), 35 kDa (P35), and 25 kDa (P25) in
      virus preparations, and with P35 in plant extracts. In extracts of the leafhopper
      vector Graminella nigrifrons fed on MCDV-infected plants, the R78 antibodies
      reacted with P25 but not with P50 and P35. The R69 antibodies bound proteins of
      approximately 36 kDa (P36), 30 kDa (P30), and 26 kDa (P26) in virus preparations,
      and P36 and P26 in plant extracts. Antibodies to R37 reacted with a 26-kDa
      protein in purified virus preparations, but not in plant extracts. Neither the
      R69 nor the R37 antibodies bound any proteins in G. nigrifrons. Thus, in addition
      to the three CPs, cysteine protease and RNA-dependent RNA polymerase, the MCDV
      polyprotein is apparently post-transitionally cleaved into P50, P35, P25, P36,
      P30, and P26.

PMID- 15246277
TI  - Effect of polyanion-resistance on HIV-1 infection.
AB  - Polyanions are potent HIV-1 entry inhibitors. Nevertheless, resistant viruses may
      emerge under polyanion inhibitory pressure. Specifically, a polyanion-resistant
      virus replicates in T cells even in the presence of high concentrations of
      polyanions. We found that although the polyanion-resistant virus grows in
      suspension CD4+ T cells efficiently, it infects nonlymphocytic adherent CD4+
      cells poorly. Given that a main distinction between suspension and adherent cells
      is the absence or presence of cell-surface heparan sulfate proteoglycan (HSPG),
      we investigated if the failure of the polyanion-resistant virus to infect
      adherent CD4+ cells arises from its inability to bind HSPG. We found that the
      emergence of mutations in gp120 associated with polyanion resistance resulted in
      a decreased capacity of HIV-1 to bind HSPG. We also found that the polycation
      polybrene rescued the capacity of the polyanion-resistant virus to bind HSPG and
      to infect adherent CD4+ cells. The identification of this virus, unable to bind
      HSPG, provides a convenient probe to measure the impact of HIV-1-HSPG
      interactions in vivo. Altogether, these findings suggest that polyanion
      resistance narrows the range of potential target cells for HIV-1 in the host.
      This reinforces the hypothesis that cell-free or cell-associated polyanions such
      as HSPG possess the capacity to modulate HIV-1 pathogenesis.

PMID- 15246278
TI  - Rack-1, GAPDH3, and actin: proteins of Myzus persicae potentially involved in the
      transcytosis of beet western yellows virus particles in the aphid.
AB  - Beet western yellows virus (BWYV) is a Polerovirus that relies on the aphid Myzus
      persicae for its transmission, in a persistent-circulative mode. To be
      transmitted, the virus must cross the midgut and the accessory salivary glands
      (ASG) epithelial barriers in a transcytosis mechanism where vector receptors
      interact with virions. In this paper, we report in vitro interaction experiments
      between BWYV and aphid components. Using the M. persicae clone from Colmar, we
      showed that a set of aphid polypeptides, separated by SDS-PAGE or 2D
      electrophoresis (2DE), can bind in vitro to purified wild type or mutant
      particles. Using subcellular fractionation, we showed that the 65-kDa polypeptide
      identified as symbionin is a soluble protein whereas the other polypeptides seem
      to be associated more or less strongly to the membrane. We hypothesize that three
      polypeptides, identified by mass spectrometry as Rack-1, GAPDH3, and actin, may
      be involved in the epithelial transcytosis of virus particles in the aphid
      vector.

PMID- 15246279
TI  - Molecular evidence of inefficient transduction of proliferating human B
      lymphocytes by VSV-pseudotyped HIV-1-derived lentivectors.
AB  - Lentiviral vectors are attractive tools to transduce dividing and nondividing
      cells. Human tonsillar B lymphocytes have been purified and induced to
      proliferate by the addition of anti-CD40 + IL-4 or anti-CD40 + anti-micro signals
      and transduced at high MOI with a VSV pseudotyped lentivector carrying the eGFP
      gene under the control of the PGK promoter. Parallel cultures of PHA-stimulated T
      lymphocytes containing a comparable amount of cycling cells during the infection
      reached over 70% eGFP transduction. By contrast, only less than 3% B lymphocytes
      became eGFP positive after 7 days from transduction. Molecular analysis of the
      viral life cycle shows that cytoplasmic retrotranscribed cDNA and nuclear 2LTR
      circles are detectable at lower levels and for a shorter period of time in
      proliferating B cells with respect to proliferating T lymphocytes. Moreover, FACS
      sorted eGFP-positive and negative B cell populations were both positive for the
      presence of retrotranscribed cDNA and 2LTR circles nuclear forms. By contrast,
      nested Alu-LTR PCR allowed us to detect an integrated provirus in FACS-sorted
      eGFP-positive cells only. Together with the demonstration that infection in
      saturation conditions led to an increase in the percentage of transduced cells
      (reaching 9%), these findings suggest that in proliferating B lymphocytes,
      lentiviral transduction is an inefficient process blocked at the early steps of
      the viral life cycle possibly involving partially saturable restriction factors.

PMID- 15246280
TI  - Antibodies against the extracellular enveloped virus B5R protein are mainly
      responsible for the EEV neutralizing capacity of vaccinia immune globulin.
AB  - In the event of smallpox bioterrorism, widespread vaccination may be required.
      Vaccinia immune globulin (VIG) has been used to treat complications from the
      smallpox vaccine. While the potency of VIG was defined by its ability to
      neutralize intracellular mature virus, a second form of vaccinia called the
      extracellular enveloped virus (EEV) is critical for virus spread in the host. The
      B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA
      revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using
      a recombinant vaccinia that lacks the majority of the extracellular domain of B5R
      showed that the ability of VIG to neutralize EEV is principally directed at B5R.
      In addition, absorbing out the anti-B5R antibody present in VIG through the
      addition of recombinant B5R protein abrogated VIG's ability to significantly
      neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a
      target of EEV-neutralizing activity of human antibodies.

PMID- 15246281
TI  - Use of alternative receptors different than alpha-dystroglycan by selected
      isolates of lymphocytic choriomeningitis virus.
AB  - Long-term infections with viruses permit the generation of variants that evolve
      specific growth advantages in certain tissues and may show altered disease
      potentials. The selection of such variants is influenced by the host tissue and
      often involves virus-receptor interactions. Here we report studies of receptor
      usage by several lymphocytic choriomeningitis virus (LCMV) isolates that
      expressed different disease patterns. Consistent with our previous studies, we
      found that, with one exception, multiple LCMV variants that cause suppression of
      immune responses bound with high affinity to their cellular receptor alpha
      dystroglycan (alpha-DG) and were dependent on alpha-DG for entry and infection.
      The exception also bound strongly to alpha-DG but was not dependent on alpha-DG
      for entry and infection. In contrast, those variants of LCMV that do not suppress
      the immune response either displayed low or no binding affinity for alpha-DG and
      used alternative receptors in addition to or instead of alpha-DG for entry and
      infection. For all alpha-DG binding variants, alpha-DG represents the preferred
      receptor in DG-expressing cells, as soluble alpha-DG blocked their infection of
      DG-deficient cells, indicating that binding of alpha-DG to the viral glycoprotein
      (GP) at the virion surface interferes with the GP's interaction with the
      alternative receptor. Biochemical characterization of the alternative receptor(s)
      for LCMV indicated that they are either protein(s) or protein-bound entities.

PMID- 15246282
TI  - A region of right posterior superior temporal sulcus responds to observed
      intentional actions.
AB  - Human adults and infants identify the actions of another agent based not only on
      its intrinsic perceptual features, but critically on the contingent relationship
      between its motion path and the environmental context [Trends Cogn. Sci. 7 (1995)
      287; Cognition 72 (2003) 237]. Functional neuroimaging studies of the perception
      of agents and intentional actions, on the other hand, have mostly focussed on the
      perception of intrinsic cues to agency, like a face or articulated body motion
      (e.g. [J. Neurosci. 17 (1997) 4302; Neuroimage 8 (1998) 221; Trends Cogn. Sci. 4
      (2000) 267; Nat. Neurosci. 3 (2000) 80; Neuroimage 13 (2001) 775; Proc. Natl.
      Acad. Sci. U.S.A. 98 (2001) 11656; Neuron 35 (2002) 1167; Neuron 34 (2002) 149,
      Neuroscience 15 (2003) 991; J. Neurosci. 23 (2003) 6819; Philos. Trans. R Soc.
      Lond. B. Biol. Sci. 358 (2003) 435]. Here we describe a region of the right
      posterior superior temporal sulcus that is sensitive not to articulated body
      motion per se, but to the relationship between the observed motion and the
      structure of the surrounding environment. From this and other aspects of the
      region's response, we hypothesize that this region is involved in the
      representation of observed intentional actions.

PMID- 15246283
TI  - Severity of neuropsychological impairment in cocaine and alcohol addiction:
      association with metabolism in the prefrontal cortex.
AB  - We used exploratory and confirmatory statistical approaches to study the severity
      of neuropsychological (NP) impairment in 42 crack/cocaine addicted subjects and
      in 112 comparison subjects (40 alcoholics and 72 controls). Twenty
      neuropsychological test indices most reliably defining predetermined cognitive
      domains were submitted to exploratory factor analysis. A four-dimensional model
      of neurocognitive function was derived: Verbal Knowledge, Visual Memory, Verbal
      Memory, and Attention/Executive functioning accounted for 63% of the variance. We
      then examined this model's association with resting glucose metabolism in the
      brain reward circuit measured with 2-deoxy-2[18F]fluoro-D-glucose positron
      emission tomography. Results revealed that (1) cocaine addicted individuals had a
      generalized mild level of neurocognitive impairment (<1 S.D. below control mean);
      and (2) controlling for age and education, relative metabolism in the
      dorsolateral prefrontal cortex significantly predicted the Visual Memory and
      Verbal Memory factors and relative metabolism in the anterior cingulate gyrus
      significantly predicted the Attention/Executive factor. Nevertheless, it remains
      to be determined whether metabolic changes in these regions are associated with
      addiction. Our results also suggest that compared to cocaine, alcohol has a more
      detrimental effect on Attention/Executive functioning, as assessed with
      traditional NP measures. We conclude that relative to other psychopathological
      disorders (such as schizophrenia), the severity of neuropsychological impairment
      in cocaine addiction is modest, albeit not indicative of the absence of
      neurocognitive dysfunction. The impact of such small differences in performance
      on quality of life, and possibly on craving and relapse, may be substantial.
      Tasks that simulate real-life decision-making or that target specific putative
      cognitive-behavioral or motivational-emotional mechanisms might offer greater
      sensitivity in characterizing the changes that accompany addiction to drugs.
      Obtaining valid estimates of alcohol use in cocaine addicted subjects is
      essential in characterizing neurocognitive functioning in individuals addicted to
      drugs.

PMID- 15246284
TI  - Right hemisphere reading mechanisms in a global alexic patient.
AB  - We investigated the implicit, or covert, reading ability of a global alexic
      patient (EA) to help determine the contribution of the right hemisphere to
      reading. Previous studies of alexic patients with left hemisphere damage have
      suggested that the ability to derive meaning from printed words that cannot be
      read out loud may reflect right hemisphere reading mechanisms. Other
      investigators have argued that residual left hemisphere abilities are sufficient
      to account for implicit reading and moreover do not require the postulation of a
      right hemisphere system that has no role in normal reading processes. However,
      few studies have assessed covert reading in patients with lesions as extensive as
      the one in EA, which affected left medial, inferior temporal-occipital cortex,
      hippocampus, splenium, and dorsal white matter. EA was presented with lexical
      decision, semantic categorization, phonemic categorization, and letter matching
      tasks. Although EA was unable to access phonology and could not overtly name
      words or letters, she was nevertheless capable of making lexical and semantic
      decisions at above chance levels, with an advantage for concrete versus abstract
      words. Her oral and written spelling were relatively intact, suggesting that
      orthographic knowledge is retained, although inaccessible through the visual
      modality. Based on her ability to access lexical and semantic information without
      contacting phonological representations, we propose that EA's implicit reading
      emerges from, and is supported, by the right hemisphere. Finally, we conclude
      that her spelling and writing abilities are supported by left hemisphere
      mechanisms.

PMID- 15246286
TI  - Covert processing of visual form in the absence of area LO.
AB  - The patient D.F., who suffers from severe visual form agnosia, has been found to
      have a bilateral lesion of area LO, an area known to be intimately involved in
      the perception of object shape. Despite her perceptual impairment, however, D.F.
      retains residual form processing abilities that can provide distal visuomotor
      control, for example in the configuration of her grasp when reaching to pick up
      objects of different shapes and sizes. This dissociation has been interpreted as
      reflecting the sparing of a dedicated system for processing the physical
      properties of objects solely for purposes of guiding action. Here we test this
      hypothesis in two studies designed to examine whether or not spared shape
      processing capacities might be revealed under other kinds of indirect test
      conditions. First, we exploited the fact that a redundant shape cue will speed
      search for a coloured stimulus within an array, and vice versa. Unlike our
      control subjects, D.F. showed no facilitation effect of either kind. Second, we
      used two Stroop tasks in which single coloured uppercase letters were presented.
      Our intention was to determine (a) whether naming the colour would be influenced
      by whether the letter was the initial letter of the correct or incorrect colour
      name (e.g. 'R' or 'G'); and (b) whether the reverse might be true, that is that
      D.F.'s guesses at letter identity might be influenced by their colour. We found
      no evidence for a Stroop effect of the former (standard) kind in D.F., but we did
      find evidence for reverse-Stroop effects. This result may reflect a partial
      sparing of ventral stream areas specialised for letter-form processing.

PMID- 15246285
TI  - Sensorimotor effects on central space representation: prism adaptation influences
      haptic and visual representations in normal subjects.
AB  - Prism adaptation improves visual and haptic manifestations of left neglect, and
      can induce a small but reliable simulation of left visual neglect in normal
      individuals. Here, we present two experiments in which the effects of prism
      adaptation on the representation of space were explored. In Experiment 1, normal
      subjects were required to locate the centre of a haptically explored circle,
      before and after adaptation to leftward displacing prisms. In Experiment 2, a
      visual circle centring task was used. In both tasks, prism adaptation induced a
      significant rightward shift of performance. In addition, in both experiments,
      three classical measures of visuo-manual adaptation were taken: the visual shift,
      the proprioceptive shift and the total shift. The effects found on the haptic and
      visual tasks did not correlate with any of these measures. This suggests that the
      effects of prism adaptation on the circle centring tasks did not depend directly
      on the sensorimotor consequences of the adaptation. These results imply that
      prism adaptation can affect noetic levels of space representation in normal
      subjects, supporting the hypothesis that this low-level sensorimotor intervention
      can exert a bottom-up structuring influence on higher levels of cognitive
      integration.

PMID- 15246287
TI  - Interhemispheric integration during the menstrual cycle: failure to confirm
      progesterone-mediated interhemispheric decoupling.
AB  - A recent theory proposed that high levels of progesterone during the menstrual
      cycle may lead to functional decoupling of the cerebral hemispheres
      [Neuropsychologia 38 (2000) 1362]. The present study tested this theory with a
      well-validated behavioral measure of interhemispheric communication administered
      to 55 naturally-cycling women at the luteal or menstrual phase of the cycle.
      Neither between-subjects nor within-subjects analyses found significant
      differences in interhemispheric communication between the menstrual and luteal
      phases (F < 1). Correlations between salivary progesterone levels and
      interhemispheric communication also failed to support the theory. Although
      negative affect (NA) was associated with decreased effectiveness of
      interhemispheric communication, mood variables could not account for the lack of
      relationship between hormonal and interhemispheric variables. In summary, despite
      a rigorous and valid test, the theory that progesterone leads to interhemispheric
      decoupling found no support.

PMID- 15246288
TI  - What do lateralized displays tell us about visual word perception? A cautionary
      indication from the word-letter effect.
AB  - A common assumption underlying laterality research is that visual field
      asymmetries in lateralized word perception indicate the hemispheric
      specialisation of processes generally available for the perception of words,
      including words viewed in a more typical setting (i.e. in the central visual
      field). We tested the validity of this assumption using a phenomenon (the word
      letter effect) frequently reported for displays viewed in the central visual
      field, where letters in words are perceived more accurately than the same letters
      in isolation. Words and isolated letters were presented in the left visual field
      (LVF), right visual field (RVF) and central visual field (CVF), the Reicher
      Wheeler task was used to suppress influences of guesswork, and an eye-tracker
      ensured central fixation. In line with previous findings, lateralized displays
      revealed a RVF-LVF advantage for words (but not isolated letters) and CVF
      displays revealed an advantage for words over isolated letters (the word-letter
      effect). However, RVF and LVF displays both produced an advantage for isolated
      letters over words (a letter-word effect), indicating that processing subserving
      the advantage for words when participants viewed stimuli in the central visual
      field was unavailable for lateralized displays. Implications of these findings
      for studies of lateralized word perception are discussed.

PMID- 15246289
TI  - Action-specific extrapolation of target motion in human visual system.
AB  - Neuropsychological studies have indicated two distinct visual pathways in our
      brain, one dedicated to conscious perception and one to visuomotor control. Some
      psychophysical results support this idea with normal subjects, but they are still
      controversial. This study provides new psychophysical evidence for the
      dissociation by showing action-specific extrapolation of the visual target
      trajectory. When a moving target disappears, the perceived final position is
      liable to be shifted forward (representational momentum). In experiment 1, larger
      and more robust forward shifts were found when the position was directly touched
      without seeing the screen (open-loop pointing) than when the position was judged
      perceptually. The most striking dissociation was that fixation did not affect the
      forward shift in open-loop pointing while it almost abolished the shifts in
      perceptual judgements. In experiment 2, this action-specific result was found to
      disappear after a response delay of 4000 ms. Experiments 3 and 4 confirmed that
      the results were not affected by the external reference frames. The specific
      forward shifts found in open-loop pointing suggest that the visuomotor system
      compensates for the neural delays by extrapolating the target motion. The
      results, together with earlier findings, lead to a psychophysical double
      dissociation of the two visual pathways.

PMID- 15246290
TI  - Effects of age on retrieval cue processing as revealed by ERPs.
AB  - The electrophysiological correlates of retrieval cue processing were investigated
      in healthy young (18-30 years) and older (63-75 years) subjects (n = 16 per
      group). Retrieval orientation--the differential processing of cues according to
      the form of the sought-for information--and retrieval difficulty were manipulated
      in a factorial design. In separate study-test cycles, subjects studied either
      words or pictures, and performed a yes/no recognition memory task with words as
      the test items. ERPs elicited by correctly classified new words differed markedly
      according to study material in the young subjects, replicating previous findings.
      In the older subjects, this effect was smaller than in the young, and had a later
      onset and earlier offset. The scalp topography of the effect was however
      statistically indistinguishable in the two groups. These age-related ERP
      differences were unmodulated by task difficulty, and remained reliable when
      recognition performance was matched across the groups. By contrast, the magnitude
      and timing of ERP difficulty effects were unaffected by age. The findings suggest
      that older subjects are less able than young individuals to vary their processing
      of retrieval cues in response to different retrieval demands.

PMID- 15246291
TI  - Structural similarity and category-specificity: a refined account.
AB  - It has been suggested that category-specific recognition disorders for natural
      objects may reflect that natural objects are more structurally (visually) similar
      than artefacts and therefore more difficult to recognize following brain damage.
      On this account one might expect a positive relationship between blood flow and
      structural similarity in areas involved in visual object recognition. Contrary to
      this expectation we report a negative relationship in that identification of
      articles of clothing cause more extensive activation than identification of
      vegetables/fruit and animals even though items from the categories of animals and
      vegetables/fruit are rated as more structurally similar than items from the
      category of articles of clothing. Given that this pattern cannot be explained in
      terms of a tradeoff between activation and accuracy, we interpret these findings
      within a model where the matching of visual forms to memory incorporates two
      operations: (i) the integration of stored object features into whole object
      representations (integral units), and (ii) the competition between activated
      integral units for selection (i.e. identification). In addition, we suggest that
      these operations are differentially affected by structural similarity in that
      high structural similarity may be beneficial for the integration of stored
      features into integral units, thus explaining the greater activation found with
      articles of clothing, whereas it may be harmful for the selection process proper
      because a greater range of candidate integral units will be activated and compete
      for selection, thus explaining the higher error rate associated with animals. We
      evaluate the model based on previous evidence from both normal subjects and
      patients with category-specific disorders and argue that this model can help
      reconcile otherwise conflicting data.

PMID- 15246292
TI  - Action observation and speech production: study on children and adults.
AB  - The present study aimed to determine whether observation of upper limb actions
      selectively influences speech production. We compared the effects on children
      with those on adults, hypothesizing that action observation is used by children
      for speech learning. Children and adults observed an actor either grasping a
      cherry or an apple, or bringing the same fruits to his mouth. They pronounced the
      syllable/ba/ at the end of the action. In a control experiment, children and
      adults executed the two bringing-to-the-mouth actions, still pronouncing/ba/. As
      previously found ([Euro. J. Neurosci., 17 (2003) 179]; [Euro. J. Neurosci., 19
      (2004) 192]), the observed kinematics of the action, which were different
      according to the fruit size, influenced lip shaping kinematics and voice
      formants. In addition, the effect was selective for the action since the
      observations of actions such as grasping and bringing-to-the-mouth affected
      formant 1 and formant 2 in the voice spectra, respectively. The effects on speech
      were greater in the children than in the adults. By contrast, the effects on lip
      shaping did not differ between the two groups. Effects similar to those found for
      action observation were found for action execution in spite of a different arm
      kinematics between children and adults. The results of the present study are
      discussed according to the hypothesis that action observation induces in the
      viewer action recognition and activation of the successive mouth act (probably
      grasping-with-the-mouth when observing grasping-with-the-hand and chewing when
      observing bringing-to-the-mouth). This subsequently seems to affect
      characteristics peculiar to the emitted vowel. This mechanism might have been
      used by humans to transfer a primitive arm gesture communication system from the
      arm to the mouth and may be further used by children for speech learning.

PMID- 15246293
TI  - The neuropsychology of visual artistic production.
AB  - What happens to visual artists with neuropsychological deficits? This review will
      examine artistic production in individuals with a variety of syndromes including
      achromatopsia, neglect, visual agnosia, aphasia, epilepsy, migraine, dementia and
      autism. From this review it appears that artists are not spared visual-motor
      deficits despite their special graphic abilities. Rather their talents allow them
      to express visual deficits with particular eloquence. By contrast, the effects of
      aphasia on art are variable. In addition to deficits, neuropsychological
      syndromes may be associated with positive phenomena. Such phenomena induced by
      epilepsy or migraines can serve to inspire artists. This review also makes clear
      that artists with neuropsychological deficits do not necessarily produce art of
      lesser quality. Rather, their art may change in content or in style, sometimes in
      surprising and aesthetically pleasing ways. The neuropsychology of visual art
      also touches on a few central questions about the nature of artistic expression
      itself. For example, what forms can artistic representations take? How are visual
      features used descriptively and expressively? What roles do knowing and seeing
      play in depiction?

PMID- 15246294
TI  - Injury severity as primary predictor of outcome in acute spinal cord injury:
      retrospective results from a large multicenter clinical trial.
AB  - BACKGROUND CONTEXT: The prognostic value of injury severity and of anatomical
      region in acute spinal cord injury is strong, making it hard to evaluate other
      indicators or assess improvement without considering them. PURPOSE: This study
      documents issues and suggests a practical way to stratify. STUDY DESIGN/SETTING:
      Retrospective analysis of data prospectively collected for the multicenter trial
      of GM-1. PATIENT SAMPLE: A total of 760 patients were recruited at 28 centers in
      North America. Injuries were rostral to T10 and left at least one leg with an
      American Spinal Injury Association (ASIA) motor score less than 15 of 25.
      Patients were assessed at baseline using the ASIA Impairment Scale (AIS): Grade
      A, Grade B, and Grades C and D (combined). They were divided by injury region:
      cervical or thoracic. OUTCOME MEASURES: The endpoint was marked recovery (MR),
      defined as improvement of at least two grades from AIS at baseline to Modified
      Benzel Scale at Week 26. Other endpoints were changes in ASIA Motor, in light
      touch, and in pin prick scores. METHODS: Data were verified onsite by a central
      team of monitors, the database was checked and standard statistical techniques
      were applied. RESULTS: Recruitment was uneven. In 760 patients, 579 injuries were
      cervical, and 482 were complete. There were few incomplete thoracic injuries. The
      cervical group had more MR than the thoracic group (37.2% vs 15.9%, p< .0001).
      AIS Groups C and D had (p< .0001) more MR (84.0%) than Group B (46.6%), which
      recovered more than Group A (12.8%). The cervical group had an advantage in MR
      because it had more patients with AIS B, and still more AIS C and D. Within AIS
      Group A, the cervical subgroup had (p< .02) higher MR (15.5%) than the thoracic
      one (7.0%), but MR was nearly equal in the B and CD groups. This suggested a new
      stratification variable, "injury region/severity," to distinguish cervical
      (n=332, MR=15.5%) and thoracic (n=150, MR=7.0%) injuries within AIS A, but not in
      AIS B (n=131, MR=46.6%) or AIS CD (n=147, MR=84.1%). This variable is a
      significant predictor of MR (p< .0001). CONCLUSIONS: AIS severity was the
      strongest predictor. Anatomical region was also strong but confounded with the
      severity effect, because the cervicals had fewer complete injuries, and because
      the cervical complete group did better than thoracic complete. The injury
      region/severity variable keeps the strong prognostic value of using both region
      and severity, but is simpler and more statistically economical.

PMID- 15246296
TI  - Is galvanic corrosion between titanium alloy and stainless steel spinal implants
      a clinical concern?
AB  - BACKGROUND CONTEXT: Surgeons are hesitant to mix components made of differing
      metal classes for fear of galvanic corrosion complications. However, in vitro
      studies have failed to show a significant potential for galvanic corrosion
      between titanium and stainless steel, the two primary metallic alloys used for
      spinal implants. Galvanic corrosion resulting from metal mixing has not been
      described in the literature for spinal implant systems. PURPOSE: To determine
      whether galvanic potential significantly affects in vitro corrosion of titanium
      and stainless steel spinal implant components during cyclical compression
      bending. STUDY DESIGN/SETTING: Bilateral spinal implant constructs consisting of
      pedicle screws, slotted connectors, 6.35-mm diameter rods and a transverse rod
      connector assembled in polyethylene test blocks were tested in vitro. Two
      constructs had stainless steel rods with mixed stainless steel (SS-SS) and
      titanium (SS-Ti) components, and two constructs had titanium rods with mixed
      stainless steel (Ti-SS) and titanium (Ti-Ti) components. METHODS: Each construct
      was immersed in phosphate-buffered saline (pH 7.4) at 37 C and tested in cyclic
      compression bending using a sinusoidal load-controlling function with a peak load
      of 300 N and a frequency of 5 Hz until a level of 5 million cycles was reached.
      The samples were then removed and analyzed visually for evidence of corrosion. In
      addition, scanning electron microscopy (SEM) and energy dispersive spectrometry
      (EDS) were used to evaluate the extent of corrosion at the interconnections.
      RESULTS: None of the constructs failed during testing. Gross observation of the
      implant components after disassembly revealed that no corrosion had occurred on
      the surface of the implants that had not been in contact with another component.
      The Ti-Ti interfaces showed some minor signs of corrosion only detectable using
      SEM and EDS. The greatest amount of corrosion occurred at the SS-SS interfaces
      and was qualitatively less at the SS-Ti and Ti-SS interfaces. CONCLUSIONS: The
      results from this study indicate that when loaded dynamically in saline,
      stainless steel implant components have a greater susceptibility to corrosion
      than titanium. Furthermore, the galvanic potential between the dissimilar metals
      does not cause a discernible effect on the corrosion of either. Although the
      mixture of titanium alloy with stainless steel is not advocated, the results of
      this study suggest that galvanic corrosion is less pronounced in SS-Ti mixed
      interfaces than in all stainless steel constructs.

PMID- 15246297
TI  - Preliminary results of staged anterior debridement and reconstruction using
      titanium mesh cages in the treatment of thoracolumbar vertebral osteomyelitis.
AB  - BACKGROUND CONTEXT: Vertebral osteomyelitis can be successfully treated with
      spinal immobilization and parenteral antibiotics. Failure of medical therapy may
      necessitate surgical treatment consisting of anterior debridement and structural
      anterior column reconstruction. Autologous structural bone graft has
      traditionally been the gold standard in anterior column reconstruction. Because
      of the morbidity related to graft harvest, vertebral body replacement cages have
      emerged as a viable option for reconstructing a deficient anterior column.
      PURPOSE: To evaluate the efficacy of titanium mesh cages in the reconstruction of
      anterior column defects in the presence of active pyogenic infection. STUDY
      DESIGN: Prospective case series. METHODS: Eleven patients underwent operative
      treatment for osteomyelitis of the thoracolumbar spine using staged anterior
      debridement and reconstruction with cylindrical titanium mesh cages followed by
      delayed posterior spinal fusion with pedicle screw instrumentation during a 2
      year period. Patients were postoperatively evaluated clinically and
      radiographically. RESULTS: Follow-up averaged 17+/-9 months. Average increase in
      kyphosis of 10+/-6 degrees corresponding to 4+/-4 mm loss in the height
      (subsidence) of the anterior construct. One patient died during revision surgery
      for hardware failure. Seven of the remaining 10 patients have not required
      antibiotics after the initial postoperative course of treatment. Three patients
      are maintained on chronic suppressive therapy as a precaution. There has been no
      evidence of recurrence or residual infection in any patient. Seven of the 10
      patients were pain free at latest follow-up. There has been one case of
      pseudarthrosis. CONCLUSION: Cylindrical titanium mesh can be used with
      consistently good results for large anterior column defect reconstructions even
      in the face of active pyogenic infection. In our cohort of patients with pyogenic
      vertebral osteomyelitis, the use of titanium mesh cages has not been associated
      with early recurrence of infection.

PMID- 15246298
TI  - Variation of the cervical spinal Torg ratio with gender and ethnicity.
AB  - BACKGROUND CONTEXT: The Torg ratio is used as a universal indicator of cervical
      canal stenosis despite reports of differences between gender and race. Normal
      values of this ratio have been established for subjects of different ethnicity,
      but the differences between genders and race have not been critically compared.
      PURPOSE: To establish normal cervical spinal dimensions and analyze the
      differences observed between men and women, and between reports using subjects of
      different ethnicity. STUDY DESIGN/SETTING: Observational. PATIENT SAMPLE: Forty
      men and 40 women of Chinese descent with no history or symptoms of neck pathology
      selected from patients presenting to the Emergency Department for foreign body
      ingestion. OUTCOME MEASURES: Measurements of the sagittal developmental diameter
      (SDD) and vertebral body diameter (VB) on the lateral cervical radiograph with
      calculation of SDD/VB (Torg ratio). METHODS: Lateral radiographs of the cervical
      spine were taken in a standardized manner with a 180-cm film-to-tube distance.
      Comparison was made between genders in the study population and with previous
      reports on subjects of different ethnicity. RESULTS: The SDD was narrowest at the
      C4 level in both men and women. Women had smaller SDDs at all levels of the
      cervical spine. Female VBs were of sizes similar to their corresponding SDDs,
      whereas men had larger VBs. This resulted in small Torg ratios in men averaging
      0.87. Comparison with previous reports demonstrated consistent variation in the
      SDD, which increased serially from Japanese, through Chinese and Indian, to white
      subjects. The relationship of VB to the corresponding SDD displayed wide
      variation between reports. This resulted in Torg ratios differing not only
      between subjects of different ethnicity but also between genders within the same
      population. CONCLUSIONS: The Torg ratio is not a consistent indicator of the SDD
      and may not be used to reliably identify the presence of cervical canal stenosis.

PMID- 15246300
TI  - Biomechanical study of pedicle screw fixation in severely osteoporotic bone.
AB  - BACKGROUND CONTEXT: Obtaining adequate purchase with standard pedicle screw
      techniques remains a challenge in poor quality bone. The development of alternate
      insertion techniques and screw designs was prompted by recognition of potential
      fixation complications. An expandable pedicle screw design has been shown to
      significantly improve fixation compared to a conventional screw in poor quality
      bone. PURPOSE: The purpose of this study was to determine if
      polymethylmethacrylate (PMMA) bone cement augmentation of an expandable pedicle
      screw can further improve fixation strength compared to the expandable screw
      alone in severely osteoporotic bone. A technique for cement insertion into the
      pedicle by means of the cannulated central portion of the expandable screw is
      also described. STUDY DESIGN: The axial pullout strength, stiffness and energy
      absorbed of cemented and noncemented expandable pedicle screws was determined in
      cadaveric vertebrae. METHODS: Twenty-one fresh unembalmed vertebrae from the
      thoracolumbar spine were used. Radiographs and bone mineral density measurements
      (BMD) were used to characterize bone quality. Paired cemented and noncemented
      pedicle screw axial pullout strength was determined through mechanical testing.
      Mechanical pullout strength, stiffness and energy to failure was correlated with
      BMD. RESULTS: Overall, there was a 250% increase in mean pullout strength with
      the cemented expandable screw compared with a noncemented expandable screw
      including a greater than twofold increase in pullout strength in the most
      severely osteoporotic bone. The mean stiffness and energy absorbed to failure was
      also significantly increased. A cemented conventional screw achieved a pullout
      strength similar to the noncemented expandable screw. CONCLUSIONS: PMMA cement
      augmentation of the expandable pedicle screw may be a viable clinical option for
      achieving fixation in severely osteoporotic bone.

PMID- 15246301
TI  - Vascular injury during anterior lumbar surgery.
AB  - BACKGROUND CONTEXT: With the number of anterior lumbar procedures expected to
      increase significantly over the next few years, it is important for spine
      surgeons to have a good understanding about the incidence of vascular
      complications during these operations. PURPOSE: To determine the incidence of
      vascular injury in 1,315 consecutive cases undergoing anterior lumbar surgery at
      various levels from L2 to S1. STUDY DESIGN/SETTING: Patients undergoing anterior
      lumbar surgery were studied. PATIENT SAMPLE: A total of 1,310 consecutive
      patients undergoing 1,315 anterior lumbar procedures between August 1997 and
      December 2002 were included in the study. OUTCOME MEASURES: All patients were
      evaluated for incidence of vascular injury during and immediately after surgery.
      METHOD: A concurrent database was maintained on all these cases. All the patients
      had distal pulse evaluation preoperatively. Patients with venous injuries were
      further analyzed to determine location and extent of injury, amount of blood
      loss, completion of the procedure and postoperative sequelae. Patients with pulse
      deficits or evidence of ischemia during or immediately after surgery were further
      analyzed in particular in relation to demographic, preoperative variables and
      management. RESULTS: Six patients were identified as having left iliac artery
      thrombosis (0.45%), and 19 had major vein lacerations (1.4%). CONCLUSION: This
      study shows that the incidence of vascular injury is relatively low (25 in 1,315
      or 1.9%). Because only five of these patients experienced significant sequelae
      from the approach, it appears that anterior lumbar surgery is quite safe,
      although it must be carried out with utmost respect for the vessels to avoid
      possible catastrophic outcomes.

PMID- 15246302
TI  - Comparison of thoracic kyphosis and postural stiffness in younger and older
      women.
AB  - BACKGROUND CONTEXT: An increase in thoracic kyphosis and postural stiffness is
      commonly associated with aging and many pathological conditions. Simple clinical
      measurements are needed to estimate the relative degree of postural stiffness to
      determine whether clinical interventions, such as exercise, are beneficial.
      PURPOSE: To compare the amount of kyphosis and postural stiffness in the thoracic
      spine of younger and older women. STUDY DESIGN/SETTING: Experimental design
      conducted at a large health science center in southeastern Texas. PATIENT SAMPLE:
      Fifty-one healthy adult women, 25 between the ages of 21 and 51 years and 26 aged
      66 to 88 years. OUTCOME MEASURES: Index of kyphosis (IK) measured with a
      surveyor's flexicurve. Differences, percent change and ratios between IK measures
      taken in the relaxed and maximally erect positions were used to estimate postural
      stiffness. METHODS: Subjects were measured while standing in their usual relaxed
      posture and again in their maximally erect posture by three different raters. IK
      measures were calculated by each rater and averaged for further data analysis.
      Independent t tests were used to compare the two age groups at the .05 alpha
      level. RESULTS: Significant differences were found in both the relaxed (p= .018)
      and erect (p< .001) IK measures of younger and older women. The differences,
      percent change and ratio between the two IK measures were also significantly
      different in that the younger women demonstrated a greater degree of active
      reduction of their kyphosis (in the erect posture) than older women. CONCLUSIONS:
      Age-related differences in thoracic kyphosis and postural stiffness were
      documented between younger and older women by means of repeated flexicurve
      measurements performed in both a relaxed and a maximally erect position.

PMID- 15246303
TI  - Acute versus chronic vertebral compression fractures treated with kyphoplasty:
      early results.
AB  - BACKGROUND CONTEXT: Kyphoplasty, a minimally invasive technique for fracture
      reduction and stabilization, has been shown to reduce pain and restore vertebral
      body height in patients with vertebral compression fractures (VCFs). Analyses
      comparing treatment outcomes of acute versus chronic VCFs have not yet been
      reported. PURPOSE: To assess whether kyphoplasty results in better clinical
      outcome and fracture reduction in patients with either acute or chronic VCFs.
      STUDY DESIGN: A prospective, consecutive cohort study of patients who underwent
      kyphoplasty between March 2000 and December 2001 to treat osteoporotic VCFs that
      were either less than 10 weeks old (acute) or more than 4 months old (chronic).
      Fifteen subacute fractures (treated 10 to 16 weeks after fracture) were excluded
      from analyses. PATIENT SAMPLE: Eighty-six VCFs in 47 patients (35 female and 12
      male) were treated during 55 kyphoplasty procedures. Mean patient age was 74
      years (range, 47 to 91). METHODS: Clinical outcomes were determined by comparison
      of preoperative and postoperative data from patient-reported indexes (pain
      assessment, pain medication usage and Oswestry Disability Index for Back Pain).
      Radiographs were assessed as to percent vertebral collapse, vertebral height
      restoration and local kyphosis correction. RESULTS: By 2 weeks after surgery, 90%
      of acute and 87% of chronic fractures were associated with pain relief. Narcotic
      usage decreased and Oswestry scores improved in almost all patients. Mean
      vertebral body height significantly improved after kyphoplasty (acute: 58% to 86%
      of estimated normal vertebral height, p< .001; chronic: 56% to 79% of estimated
      normal vertebral height, p< .001). Restoration to 89% or greater estimated normal
      vertebral height was achieved in 60% of acute fractures and 26% of chronic
      fractures. In addition, more acute fractures were reducible (greater than 80%
      restoration of height lost) compared with chronic fractures (p= .01). After
      kyphoplasty, less than 10% correction of height lost occurred in 8% of acute
      fractures and 20% of chronic fractures. Local kyphosis significantly improved
      after kyphoplasty (mean local Cobb angle: acute, 15 to 8 degrees, p< .001;
      chronic, 15 to 10 degrees, p< .001). CONCLUSION: Fracture reduction was best
      achieved in acute fractures. Symptomatic chronic fractures may also remain
      candidates for kyphoplasty because pain relief and improvement in patient
      function are reliable and some kyphosis correction can still be achieved in many
      of these patients.

PMID- 15246305
TI  - Can a patient educational book change behavior and reduce pain in chronic low
      back pain patients?
AB  - BACKGROUND CONTEXT: This study was prompted by 1) the almost universal use of
      patient education as an initial or at least an ancillary step in the treatment of
      patients presenting with low back pain, 2) the relative dearth of studies
      evaluating the effectiveness of patient education and 3) the complete lack of
      support in the few existing studies for the efficacy of education in improving
      patients' long-term health status. PURPOSE: A feasibility study to evaluate the
      efficacy of an individualized biomechanical treatment educational booklet to
      effect improvement in health status. STUDY DESIGN: A prospective, longitudinal
      cohort study. PATIENT SAMPLE: Sixty-two subjects (35 female, 27 male), average
      age 42.4 years, reported a mean duration of back pain before inclusion of 10.4
      years. However, because of attrition, only 48 subjects had complete data across
      the 18-month follow-up period. OUTCOME MEASURES: Outcome measures included pain
      status, number of back pain episodes, subject compliance with self-care
      behaviors, knowledge and opinion of booklet content. METHODS: Volunteers with
      chronic low back pain were provided a copy of an individualized biomechanical
      treatment educational book and told they would undergo a written survey of its
      content 1 week after reading the book. Subjects' health status at 9 and 18 months
      was evaluated using a structured telephone interview. RESULTS: One week after the
      62 subjects, with an average of 10.4 years of symptoms and extensive use of the
      medical system, finished reading the index book, 51.62% reported noticeable
      improvement in their pain, their content comprehension was good and opinions
      about the text were generally positive. At 9-month follow-up, there was
      statistically significant and clinically relevant improvement in reported pain
      magnitude (p< .03), number of episodes (p< .0001) and perceived benefit (p< .04).
      At 18-month follow-up, these gains held or demonstrated even further improvement.
      CONCLUSION: This study's results suggest that the Treat Your Own Back book may
      have considerable efficacy in helping readers decrease their own low back pain
      and reduce the frequency of, or even eliminate, their recurrent episodes. These
      findings also justify conducting a randomized controlled clinical trial to assess
      this book's efficacy in improving health status in subjects with low back pain
      with the study design including internal controls to minimize bias issues and a
      wider range of outcomes, including measures of pain, function, disability,
      patient satisfaction, utilization of health care services and psychosocial
      measures.

PMID- 15246306
TI  - Psychotropic medication in chronic spinal disorders.
AB  - BACKGROUND CONTEXT: Optimal treatment of nonmalignant chronic spinal disorders
      (CSDs) may require the use of one or more nonopioid psychotropic medications.
      Vast research literature has documented high rates of psychiatric disorders in
      patients with CSDs. Psychotropic medications are one type of effective treatment
      for these disorders. Many medications of this type are also used as adjuvants to
      primary analgesic medications. PURPOSE: Physicians treating CSDs may have little
      training and experience in prescribing psychotropic medications. Further, they
      may possess limited information about the efficacy of these types of medications
      in treating psychiatric disorders comorbid with CSDs or as adjunctive analgesics.
      Because of the wide variety (antidepressants, anxiolytics, sleep-promoting
      agents, anticonvulsants, neuroleptics, muscle relaxants) and numerous indications
      for psychiatric medications, a concise review of the use of psychotropic
      medications with CSD patients is offered for the spine specialist. STUDY DESIGN:
      A systematic review of the contemporary English literature on psychotropic
      medications in the CSD population. METHODS: A computerized search of MEDLINE was
      performed on all English literature published from 1982 to August 2002. RESULTS:
      Psychotropic medications have been found to be very efficacious in the large
      subgroup of patients with CSDs with psychiatric comorbidity, particularly
      patients with the common constellation of depression, anxiety, excessive somatic
      complaints, insomnia and irritability. Although the type of medication indicated
      depends on the particular psychiatric syndrome(s), antidepressants have been
      found to be extremely useful with the constellation described above. There is
      less evidence to support the use of nonopioid psychotropic medications in the
      treatment of nociceptive pain, although clinical experience indicates that some
      individuals demonstrate a marked analgesic response. Research support for the
      efficacy of particular psychotropic medications in treating neuropathic pain is
      stronger, although more controlled research is clearly needed. CONCLUSIONS:
      Psychotropic medications are extremely useful in the treatment of psychiatric
      disorders comorbid with CSDs and modestly useful as analgesic adjuvants,
      particularly with pain of neuropathic etiology. Familiarity with these
      medications will aid the primary treating physician in optimizing outcomes in
      this difficult group of patients.

PMID- 15246307
TI  - Pathophysiology and pharmacologic treatment of acute spinal cord injury.
AB  - BACKGROUND CONTEXT: The past three decades have witnessed increasing interest in
      strategies to improve neurologic function after spinal cord injury. As progress
      is made in our understanding of the pathophysiologic events that occur after
      acute spinal cord injury, neuroprotective agents are being developed. PURPOSE:
      Clinicians who treat acute spinal cord injuries should have a basic understanding
      of the pathophysiologic processes that are initiated after the spinal cord has
      been injured. A familiarity with the literature on which the current use of
      methylprednisolone is based is also essential. STUDY DESIGN/SETTING: Literature
      review. METHODS: Literature review of animal data on pathophysiologic mechanisms,
      and of both animal and human trials of neuroprotective agents. RESULTS: The
      mechanical forces imparted to the spinal cord cause primary damage to the neural
      tissue, but a complex cascade of pathophysiologic processes that imperil
      adjacent, initially spared tissue to secondary damage rapidly follows this.
      Attenuating this secondary damage with neuroprotective strategies requires an
      understanding of these pathophysiologic processes. Many researchers are
      investigating the role of such processes as ischemia, inflammation, ionic
      homeostasis and apoptotic cell death in the secondary injury cascade, with hopes
      of developing specific therapies to diminish their injurious effects. Beyond
      methylprednisolone, a number of other pharmacologic treatments have been
      investigated for the acute treatment of spinal cord injury, and even more are on
      the horizon as potential therapies. CONCLUSIONS: This review summarizes some of
      the important pathophysiologic processes involved in secondary damage after
      spinal cord injury and discusses a number of pharmacologic therapies that have
      either been studied or have future potential for this devastating injury.

PMID- 15246308
TI  - Adverse central nervous system sequelae after selective transforaminal block: the
      role of corticosteroids.
AB  - BACKGROUND CONTEXT: Selective transforaminal epidural injections are frequently
      employed in the treatment of pain emanating from the spine. Complication rates
      are typically low and include paresthesia, hematoma, epidural abscess,
      meningitis, arachnoiditis and inadvertent subdural or subarachnoid injection.
      Persistent paraplegia after lumbar transforaminal block has been recently
      reported. Undetected intra-arterial injection has been implicated as a possible
      cause. PURPOSE: We present a case of massive cerebellar infarction after
      uneventful selective cervical transforaminal block. Intra-arterial injection of
      corticosteroid is implicated with focus on particulate size of compound versus
      blood vessel dimension. Light microscopic data are presented to confirm the
      potential for embolic vascular occlusion. STUDY DESIGN/SETTING: Case report;
      light microscopic data. PATIENT SAMPLE: A patient underwent selective
      transforaminal block on the right at the C5-C6 level. There was C5-C6 disc
      herniation documented by magnetic resonance imaging and C6 radiculopathy by
      electromyographic studies. OUTCOME MEASURES: Patient follow-up from medical
      office records. METHODS: Needle placement at the C5-C6 foramen on the right was
      confirmed by biplanar fluoroscopy and injection of contrast medium. Frequent heme
      negative aspirations were documented. RESULTS: In this patient, quadriparesis
      ensued shortly after injection of corticosteroid solution. The patient was
      admitted to the neurosurgical intensive care unit and ultimately underwent
      brainstem decompressive surgery when focal neurologic deficits became evident.
      Working diagnosis was massive cerebellar infarct. Light microscopic data are
      presented to illustrate particulate size in corticosteroid solutions and
      potential for embolic microvascular occlusion. Corticosteroid suspensions (and to
      a lesser extent solutions) contain large particles capable of occluding
      metarterioles and arterioles. CONCLUSIONS: We present a case of quadriparesis and
      brainstem herniation after selective cervical transforaminal block. We propose a
      potential role for corticosteroid particulate embolus during unintended intra
      arterial injection as a potential mechanism.

PMID- 15246309
TI  - Percutaneous vertebroplasty through a transdiscal access route after lumbar
      transpedicular instrumentation.
AB  - BACKGROUND CONTEXT: Transpedicular vertebroplasty is an effective procedure to
      reduce pain and stabilize osteoporotic vertebral fractures. It is, however,
      difficult to perform after transpedicular instrumentation because the pedicle
      screws are in the way. PURPOSE: To determine if vertebroplasty can be performed
      in patients who have previously undergone osteosynthesis pedicle-screw fixation.
      STUDY DESIGN: We postulate that an alternate transdiscal route can be used in
      cases with instrumentation in order to successfully perform vertebroplasty.
      METHODS: We report the case of a 73-year-old male patient presenting with a fresh
      osteoporotic fracture of L2 and L3 6 weeks after having undergone a dorsal
      operative stabilization between L3 and L5. RESULTS: Vertebroplasty was performed
      using a transdiscal descending approach to treat the two adjacent vertebral
      levels. The patient reported a 50% decrease in pain and was able to walk with a
      stick at 3 months. At late follow-up at 18 months his walking had further
      improved and he experienced only sporadic lumbar pain. CONCLUSIONS:
      Vertebroplasty can be performed in patients having previously undergone
      transpedicular instrumentation. The transdiscal route represents such a new
      approach.

PMID- 15246310
TI  - Adolescent idiopathic scoliosis, bracing and the Hueter-Volkmann principle.

PMID- 15246312
TI  - Failed back surgery: etiology and diagnostic evaluation.

PMID- 15246314
TI  - Disease eradication, elimination and control: the need for accurate and
      consistent usage.
AB  - This article seeks to clarify the terminology associated with disease control,
      elimination and eradication programmes. There are several global activities under
      way, which are initiated and guided by resolutions of the World Health Assembly.
      Scrutiny of the feasibility of achieving eradication goals by bodies such as the
      International Task Force for Disease Eradication has identified diseases that
      could be eradicated. The criteria for this attribution as eradicable, the
      definitions guiding policy, and examples of programmes and strategies are
      provided here. This article pleads for scientific, health policy and editorial
      communities to be more consistent in the use of the terms control, elimination
      and eradication, and to adhere to published definitions.

PMID- 15246315
TI  - Lymphatic filariasis and Brugia timori: prospects for elimination.
AB  - Brugia timori is a pathogenic filarial nematode of humans, replacing the closely
      related species Brugia malayi on some islands in eastern Indonesia. Recent
      studies on Alor island show that, locally, B. timori is still of great public
      health importance, causing mainly acute filarial fever and chronic lymphedema.
      PCR-based assays to detect parasite DNA, in addition to assays for detecting
      specific antibodies that have been originally developed for B. malayi, can be
      used efficiently as diagnostic tools for B. timori. In the framework of the
      Global Program to Eliminate Lymphatic Filariasis, a single annual dose of
      diethylcarbamazine, in combination with albendazole, was found to reduce the
      prevalence and density of microfilaraemia persistently. Therefore, elimination of
      B. timori appears to be achievable.

PMID- 15246316
TI  - Genomics meets transgenics in search of the elusive Cryptosporidium drug target.
AB  - Cryptosporidium is an important pathogen of humans, and a challenging model for
      the laboratory. The parasite genome sequence, accessible through a comprehensive
      database, now provides exciting opportunities for urgently needed advances.
      Comparative genomics, combined with the genetic system in the related parasite
      Toxoplasma gondii, outlines a detailed Cryptosporidium parvum metabolic map and
      facilitates cell biological analyses. New targets for Cryptosporidium drug and
      vaccine development can be identified and validated based on this approach.

PMID- 15246317
TI  - Presbytis entellus: a primate model for parasitic disease research.

PMID- 15246318
TI  - Distinguishing periportal fibrosis from portal fibrosis in hepatic
      schistosomiasis.

PMID- 15246319
TI  - L-arginine metabolism during interaction of Trypanosoma cruzi with host cells.
AB  - Trypanosoma cruzi invades a diversity of nucleated cells in the mammalian host.
      Macrophages are among the first cells to be parasitized and, after activation by
      inflammatory stimuli, they participate in the control of infection. However, some
      parasites manage to evade the immune response and establish a chronic infection
      in differentiated cells. L-arginine is located at the crossroads of divergent
      routes that produce metabolites, including nitric oxide and polyamines, which
      influence the outcome (i.e. resolution or progression) of infection. This article
      discusses the fate and actions of L-arginine-derived biomolecules formed both in
      the host and in the parasite during T. cruzi-host-cell interactions.

PMID- 15246320
TI  - Intravascular schistosomes and complement.
AB  - Schistosomes are exposed to a variety of immunological effectors, such as host
      complement, in the bloodstream of their definitive hosts. The parasites are
      reported to possess a plethora of regulatory proteins, including molecules
      acquired from the host, which impede the complement cascade. Evidence for the
      presence of a surface C2-binding protein, a C3-binding protein and a C8- and C9
      binding protein has been reported. In addition, a surface Fc receptor might bind
      immunoglobulin and limit its ability to fix complement. However, the actual
      protective role of these proteins in vivo remains unresolved.

PMID- 15246321
TI  - Programmed cell death in trypanosomatids: a way to maximize their biological
      fitness?
AB  - Programmed cell death (PCD) is a biochemical process that plays an essential role
      in the development of multicellular organisms. However, accumulating evidence
      indicates that PCD is also present in single-celled eukaryotes. Thus,
      trypanosomatids might be endowed with a PCD mechanism that is derived from
      ancestral death machinery. PCD in trypanosomatids could be a process without a
      defined function, inherited through eukaryotic cell evolution, which might be
      triggered in response to diverse stimuli and stress conditions. However, recent
      observations suggest that PCD might be used by trypanosomatids to maximize their
      biological fitness. Therefore, PCD could represent a potential pharmacological
      target for protozoan control.

PMID- 15246322
TI  - Topoisomerases of kinetoplastid parasites as potential chemotherapeutic targets.
AB  - The protozoan parasites Trypanosoma, Leishmania and Crithidia, which belong to
      the order kinetoplastidae, emerge from the most ancient eukaryotic lineages. The
      diversity found in the life cycle of these organisms must be directed by genetic
      events, wherein topoisomerases play an important role in cellular processes
      affecting the topology and organization of intracellular DNA. Topoisomerases are
      valuable as potential drug targets because they have indispensable function in
      cell biology. This review summarizes what is known about topoisomerase genes and
      proteins of kinetoplastid parasites and the roles of these enzymes as targets for
      therapeutic agents.

PMID- 15246323
TI  - Assessing the effect of natural selection in malaria parasites.
AB  - There are few concepts that have been used across disciplines; one of them is
      natural selection. The impact that this process has on parasite genetic diversity
      is reviewed here by discussing examples on drug resistance and vaccine antigens.
      Emphasis is made on how mechanisms need to be addressed rather than associations,
      and how such investigations were out of reach of biomedical researchers only a
      decade ago.

PMID- 15246324
TI  - Modeling diarrhea disease in children less than 5 years old.
AB  - PURPOSE: Identification of the temporal pattern of diarrhea disease in children
      less than 5 years of age in Rio de Janeiro City (1995-1998) to provide support
      for decisions about prevention and control of the disease. METHODS: The weekly
      counts of hospitalizations and deaths due to diarrhea disease were analyzed
      separately. An initial generalized linear model (GLM) was derived using variables
      related to weather and month. Displays of fitted generalized additive models
      (GAM) including a spline smoothed function of time suggested additional
      predictors that were used to obtain new models. RESULTS: The initial models did
      not properly account for the observed cyclical pattern of the data. Graphical
      displays of the GAM model show a nonhomogeneous decline and annual cycles.
      Stepwise fitting of GLMs with two factors (cycle and season), and a time trend,
      showed that the full three-way interaction model was required. Plots of the
      residuals from the death model suggested a mixture of distributions while the
      residuals from the hospitalization model were approximately normal. CONCLUSIONS:
      The same general pattern for both time series was found by graphical inspection
      and fitting of appropriate GLMs. This study provides some additional evidence
      that severe cases of diarrhea disease may be attributed to rotavirus.

PMID- 15246325
TI  - Assessing the social class of children from parental information to study
      possible social inequalities in health outcomes.
AB  - PURPOSE: When the subjects are children, the assessment of social class must be
      made indirectly from parental data. We propose correspondence analysis as a
      method for combining parental information. METHODS: Four assessment methods were
      used: father's occupation, mother's occupation, dominant occupation of both, and
      both combined by means of a correspondence analysis. The results were used to
      explore social inequalities in dental health. We used data from a survey
      performed on school children (12- and 15-16-year olds) in the Comunitat
      Valenciana (Spain). Dental health was measured through prevalence of caries,
      number of teeth with caries, number of caries in permanent teeth, decayed,
      missing, and filled teeth score (DMF-T), decayed, missing, and filled surface
      score (DMF-S), prevalence of DMF>0, community periodontal index of treatment
      needs (CPITN) and prevalence of CPITN>0. RESULTS: Correspondence analysis methods
      reflect the impact of social class on health indicators. They were able to assign
      a social group to all individuals. The association between social class and oral
      health was found to be sensitive to the method used. CONCLUSIONS: Pooling
      information from both parents is important. Evidence of social inequalities in
      oral health may or may not be obtained depending on the method used.

PMID- 15246326
TI  - Recency affects reporting accuracy of children's dietary recalls.
AB  - PURPOSE: This study evaluated the effect of recency on accuracy of fourth
      graders' dietary reports. METHODS: Each of 60 randomly selected children was
      observed eating school meals (breakfast, lunch) and interviewed to obtain a 24
      hour dietary recall using one of six conditions generated by crossing two target
      periods (previous day, prior 24 hours) with three interview times (morning,
      afternoon, evening), with 10 children (5 males) per condition. Accuracy of the
      school meal portions of each recall was assessed by comparing reports to
      observations. Rates for omissions (items observed but not reported) and
      intrusions (items reported but not observed) were calculated to determine
      accuracy for reporting items. A measure of total inaccuracy combined errors for
      reporting items and amounts. RESULTS: Using the prior 24 hours as the target
      period yielded better performance than did using the previous day: Omission rates
      were lower by about one-third, intrusion rates by about one-half, and total
      inaccuracy by about one-third (all p's<0.01). A marginally significant
      interaction of target period by interview time was found for omission rate
      (p=0.08), but not for intrusion rate (p=0.15) or for total inaccuracy (p=0.47).
      CONCLUSIONS: This provides evidence that recency influences children's recall
      accuracy and demonstrates the importance of an awareness of principles of memory
      when designing what are essentially memory tests for epidemiologic studies.

PMID- 15246327
TI  - Leisure time physical activity and mortality in Hong Kong: case-control study of
      all adult deaths in 1998.
AB  - PURPOSE: Physical activity is associated with longevity; however, whether these
      beneficial effects extend to Chinese populations is unclear. We examined the
      relationship between leisure time physical activity (LTPA) and mortality in Hong
      Kong. METHODS: Using a case-control study, past (10 years prior) levels of LTPA
      were ascertained via proxy informants for 24,079 dead cases (81% of all
      registered deaths) and 13,054 live controls aged #10878;35 years and were
      analyzed by unmatched logistic regression to determine their association with all
      cause and cause-specific mortality. RESULTS: Compared with an exercise frequency
      of <1 episode per month, > or = 1 episode of LTPA per month was inversely
      associated with all-cause mortality [multivariable odds ratio (OR)=0.63, 95%
      confidence interval (CI), 0.59, 0.68 for males; OR=0.75, 95% CI, 0.70, 0.80 for
      females; adjusted for age, education, smoking status, alcohol consumption, and
      physical demand at work]. Each activity level above the reference level of <1
      episode per month (i.e., 1 episode per month to 1-3 episodes per week, > or = 4
      episodes per week) had approximately the same level of risk reduction and no dose
      response gradient was observed. The inverse association was stronger for
      cardiovascular than cancer deaths, particularly in males and was strongest for
      respiratory mortality. One-fifth of all 31,349 registered deaths in those aged 35
      years and over in Hong Kong in 1998 were attributable to physical inactivity.
      CONCLUSION: The present data confirm and extend previous findings in Caucasian
      populations on the association between leisure time physical activity and
      longevity. The population attributable risk from physical inactivity exceeds that
      due to tobacco smoking in this Hong Kong Chinese population. We predict mainland
      China will witness a similarly large mortality burden as it undergoes further
      socioeconomic development in the next few decades.

PMID- 15246328
TI  - Total cholesterol and mortality in China, Poland, Russia, and the US.
AB  - PURPOSE: To examine the relationships of total and cause-specific mortality to
      serum cholesterol in four diverse populations. METHODS: Chinese, Polish, Russian,
      and US population-based samples were studied. The relationship between
      cholesterol levels and mortality was assessed by Cox proportional hazard
      regression with restricted piecewise cubic splines. RESULTS: The cholesterol and
      total mortality relationship was statistically significantly J-shaped for all men
      combined. In country-specific relationships, cholesterol was significantly,
      linearly, and positively related to total mortality in Russian and US men. For
      women, the relationship was non-linear, but not statistically significant, and
      became statistically significant upon adjustment for other risk factors. For
      Polish women, a statistically significant inverse relationship existed. CHD
      mortality and cardiovascular disease (CVD) mortality increased linearly with
      cholesterol in Polish, Russian, and US men and the aggregate of men, but there
      was no relationship for women. Cancer mortality was not related to cholesterol
      except for the Polish cohort and Russian women, where there was an inverse
      relationship. CONCLUSIONS: Serum cholesterol was a strong, consistent predictor
      of CHD and CVD mortality in Polish, Russian, and US men despite their social
      diversity. In contrast to CHD mortality, the relation of cholesterol to total
      mortality and non-CVD mortality varied by country and gender.

PMID- 15246329
TI  - Comparison of the college alumnus questionnaire physical activity index with
      objective monitoring.
AB  - PURPOSE: Two methods of measuring physical activity (PA) were compared over a
      consecutive 7-day period among 25 adults (12 men and 13 women). METHODS: Each day
      estimates of energy expended in light, moderate, vigorous, and total PA were
      derived from the simultaneous heart-rate motion sensor (HR+M) technique. At the
      end of the 7-day period participants completed the College Alumnus Questionnaire
      Physical Activity Index (CAQ-PAI) and results were compared with HR+M technique
      estimates. RESULTS: Correlations between the two methods in the four activity
      categories ranged from r=0.20 to r=0.47, with vigorous and total PA showing
      higher associations than light and moderate PA. Mean levels of PA (MET-minxwk(
      1)) obtained using the two methods were similar in the moderate and vigorous
      categories, but individual differences were large. Energy expended in light PA
      was significantly underestimated on the CAQ-PAI, resulting in lower total
      activity scores on this questionnaire as compared with the HR+M. CONCLUSIONS: The
      CAQ-PAI accurately reflected mean moderate and vigorous activity in comparison
      with the HR+M technique. The results are consistent with other studies which have
      shown that physical activity questionnaires are better at assessing vigorous PA
      than ubiquitous light-moderate activities.

PMID- 15246330
TI  - Synergism between smoking and vital exhaustion in the risk of ischemic stroke:
      evidence from the ARIC study.
AB  - PURPOSE: To examine the synergism between vital exhaustion and cigarette smoking
      in producing ischemic stroke. Vital exhaustion (VE), a state characterized by
      unusual fatigue, irritability, and feelings of demoralization, is measured by the
      Maastricht questionnaire (MQ), a 21-item inventory of symptoms. METHODS: The
      Atherosclerosis Risk in Communities (ARIC) Study is an ongoing cohort study,
      initiated in 1987. The MQ was administered at the second follow-up visit (1990
      1992), and participants were subsequently followed for an average of 6.27 years.
      Four US communities (Minneapolis, Minnesota; Washington County, Maryland; Forsyth
      County, North Carolina; and Jackson, Mississippi). 13,066 participants aged 48 to
      67 years at baseline (Visit 2) with no history of stroke. Validated hospitalized
      ischemic stroke. RESULTS: During the follow-up period, there were 202 incident
      ischemic strokes. After multivariate adjustment, current smoking, and high VE
      were independent risk factors for incident stroke: (smoking vs. non-smoking
      HR=1.76, p < 0.01; high VE vs. low VE HR=1.94, p < 0.01). For persons with both
      VE and smoking vs. persons with neither, HR=2.71 (p < 0.001). The proportion of
      stroke disease burden due to VE and smoking that could be attributed to their
      interaction was 81 to 93 percent. CONCLUSIONS: The combination of cigarette
      smoking and VE is synergistic in the production of stroke.

PMID- 15246331
TI  - Associations between white blood cell count and risk for cerebrovascular disease
      mortality: NHANES II Mortality Study, 1976-1992.
AB  - PURPOSE: To examine associations between elevated white blood cell count (WBC)
      and cerebrovascular disease (CeVD) mortality independent of cigarette smoking and
      by gender. METHODS: We used Cox regression analyses of data from 8459 adults
      (3982 men; 4477 women) aged 30 to 75 years in the NHANES II Mortality Study (1976
      1992) to estimate the relative risk of death from CeVD across quartiles of WBC.
      RESULTS: During 17 years of follow-up, there were 192 deaths from CeVD (93 men;
      99 women). Compared with those with WBC (cells/mm(3))<5700, adults with WBC>8200
      were at increased risk of CeVD mortality (relative risk [RR], 2.1; 95% confidence
      interval [CI], 1.2-3.7) after adjustment for smoking and other cardiovascular
      disease risk factors. Similar results were observed among never smokers (RR, 2.0;
      95% CI, 1.0-3.8). The adjusted relative risk of CeVD mortality comparing those
      with WBC>8200 to those with WBC<5700 was 1.5 (95% CI, 0.7-3.5) among men and 2.7
      (95% CI, 1.4-5.0) among women. CONCLUSIONS: Elevated WBC may predict CeVD
      mortality even after considering the effects of smoking and other cardiovascular
      disease risk factors.

PMID- 15246332
TI  - The association of Rose questionnaire angina pectoris and coronary calcification
      in a general population: the Rotterdam Coronary Calcification Study.
AB  - PURPOSE: The Rose questionnaire is a standardized method of measuring angina
      pectoris in general populations. Electron-beam computed tomography (CT) is a non
      invasive technique to quantify the amount of coronary calcification. In a
      population-based study, we investigated the association between Rose
      questionnaire angina pectoris and coronary calcification. METHODS: The Rotterdam
      Coronary Calcification Study is embedded in the Rotterdam Study, a population
      based study in subjects aged > or = 55 years. Participants of the Rotterdam
      Coronary Calcification Study underwent an electron-beam CT scan between 1997 and
      2000. Coronary calcification was quantified in a calcium score according to
      Agatston's method. Rose questionnaire angina pectoris was assessed during a home
      interview. The first 2013 participants were included in the present analyses.
      RESULTS: In men, the presence of Rose questionnaire angina pectoris was
      associated with a 12.9-fold (95% confidence interval: 3.8-43.7) increased risk of
      a calcium score >1000 (reference: calcium score 0-100). The corresponding
      relative risk in women was 4.8 (2.0-11.3). Similar results were found when we
      computed sex-specific quartiles of the calcium score. CONCLUSIONS: Rose
      questionnaire angina pectoris is strongly associated with the amount of coronary
      calcification. Rose questionnaire angina pectoris corresponds better with the
      amount of coronary calcification in men than in women.

PMID- 15246333
TI  - Investigating the effect of nonparticipation using a population-based case
      control study on myocardial infarction.
AB  - PURPOSE: To characterize non-participants in a population-based study on
      cardiovascular diseases and investigate the effect of non-participation on risk
      estimates for myocardial infarction. METHODS: Using random digit dialing we
      obtained full information for 1054 adults (60.8% female), while 345 eligible
      individuals (72.5% female) declined the invitation to participate, but answered a
      limited set of questions by telephone. Risk of myocardial infarction was
      estimated using 474 cases (19.4% females) admitted with a first acute myocardial
      infarction. RESULTS: Participation proportion was 99.0% for cases and 70.0% for
      population controls. Population non-participants were older (61.6 vs. 58.5 years,
      for males, and 62.9 vs. 57.7 years for females) and more frequently women (66.3%
      vs. 74.7%, p < 0.001); males tended to be non-drinkers and to have had a blood
      test during the previous year; females were additionally more often non-smokers.
      Crude and adjusted risk estimates for myocardial infarction were generally
      similar regardless of considering the information provided by non-participants.
      CONCLUSIONS: In this South European population, demographic and social
      characteristics associated with the decision to participate in a community
      investigation were different from those usually described in Northern European or
      American populations. However, their characteristics did not influence the
      direction or the magnitude of myocardial infarction risk estimates.

PMID- 15246334
TI  - Changes in mortality after the recent economic crisis in South Korea.
AB  - PURPOSE: To examine the changes in all cause mortality and cause-specific
      mortality after the economic crisis in South Korea. METHODS: Monthly mortality
      data for an entire country was used and intervention analysis applied to compare
      mortality after the crisis with mortality which would have occurred if the trends
      before the crisis had continued. RESULTS: All cause mortality began to increase
      about 1 year after the crisis, while cardiovascular increased immediately.
      Transport accidents decreased significantly during the year following the crisis
      and then regressed towards the pre-economic crisis level. Suicides increased
      rapidly and maintained an upward trend but subsequently reduced towards the pre
      economic crisis level. CONCLUSIONS: This study has shown an evidence of a
      relationship between economic crisis and mortality.

PMID- 15246335
TI  - The functional anatomy of neuropathic pain.
AB  - The generation of neuropathic pain is a complex phenomenon involving a process of
      peripheral and central sensitization producing enhanced transmission of
      nociceptive inputs to the brain associated with the loss of discriminatory
      processing of noxious and innocuous stimuli. This increased flow of abnormally
      processed nociceptive inputs to the brain may overcome the ability of descending
      modulatory pathways to produce analgesia, causing further worsening of the pain.
      Several crucial locations involved in the physiologic generation of pain inputs
      (eg, peripheral nociceptors, dorsal horns, thalamus, cortex) show evidence of
      functional reorganization and altered nociceptive processing in association with
      chronic pain. These locations present the best targets for therapeutic
      intervention, including systemic administration of drugs able to counteract the
      chemical storm induced by neural injuries in the nociceptive afferents and dorsal
      horns, or for more focused intervention, such as neuroablative procedures;
      intrathecal drug delivery; and spinal cord, deep brain, or motor cortex
      stimulation.

PMID- 15246336
TI  - Functional imaging and the neural systems of chronic pain.
AB  - Pain remains a serious health care problem affecting millions of individuals,
      costing billions of dollars, and causing an immeasurable amount of human
      suffering. In designing improved therapies, there is still much to learn about
      peripheral nociceptor, nerves, and the spinal cord, and brain stem modulatory
      systems. Nevertheless, it is the brain that presents us with an incredible
      opportunity to understand the experience we call pain. Functional neuroimaging is
      helping to unlock the secrets of the sensory and emotional components of pain and
      its autonomic responses. These techniques are helping us to understand that pain
      is not a static disease with the pathologic findings localized to the periphery
      but is instead a highly plastic condition affecting multiple central neural
      systems. Functional neuroimaging is transforming our understanding of the
      neurobiology of pain and will be instrumental in helping us to design more
      rational treatments ultimately aimed at reducing the impact of pain on our
      patients. It is opening windows into the function of the brain that were
      previously closed.

PMID- 15246337
TI  - Intrathecal methods.
AB  - Although the use of opioids for intrathecal anesthesia was first reported in
      1901, it was not until 25 years ago that the first report of selective blockade
      of pain by spinal opioids was described. Since its beginning, the promise of
      selective analgesics derived from intraspinal administration has generated much
      development in the field of pain management. In fact, many anesthesiologists who
      had previously relegated themselves to the confines of the operating room
      discovered that their needles and catheters could reach even beyond the inpatient
      wards, affording patients outside the hospital the opportunity to receive
      neuraxial drugs. The goal of this article is to report on the current state of
      spinal analgesic chemotherapy as it is now known.

PMID- 15246338
TI  - Spinal cord stimulation in chronic pain management.
AB  - As a general rule, even though it is always difficult to predict the efficacy of
      a method ina single patient, we consider SCS in every non-malignant chronic pain
      patient when other conservative treatments have failed. After three decades of
      clinical experience with SCS, we have learned a lot about its efficacy
      indifferent pain conditions and have made great technical progress with the
      materials and surgical procedures. Acceptance of the technique was slow at the
      beginning; however, we must be aware of the problems related to the application
      of a therapy that cannot be shamed, and thus the necessity of performing studies
      that include large numbers of patients. This is even more complicated when
      dealing with pain patients because of the well-known multifactoriality of pain.
      Nowadays, every algorithm for the treatment of different pain conditions includes
      SCS; consequently, every pain center should be able to offer this therapy in its
      treatment program. This article discusses what has been learned so far with
      regard to SCS, but there is a lot more to learn about this technique as well as
      about other types of neuromodulation procedures. As mentioned in the introduction
      of this article and discussed in the section on the effects of SCS, particularly
      in clinical applications like peripheral vascular disease and angina, the results
      of the interaction with the function of the nervous system can be observed in
      other systems in the body affecting pathologic conditions that are of interest to
      different specialists. Only the strict cooperation of different medical
      disciplines can provide substantial help in acquiring knowledge about the
      mechanisms put into play by SCS and the possible extension of its clinical
      applications. The complexity of the procedures of neuromodulation and the
      theoretic background needed for safe and proficient clinical use and for progress
      raise the issue for medical schools of offering courses in this new discipline.

PMID- 15246339
TI  - The surgical treatment of chronic pain: destructive therapies in the spinal cord.
AB  - Stereotactic pain surgery is accepted as a group of procedures. These are usually
      highly sophisticated and technically risky procedures. In practice, the most
      important part of this discipline is not the technical abilities of the surgeon,
      but selection of the most appropriate patients for the available procedures. We
      must remember that we are performing all these procedures with the cooperation of
      patients. The energy that is used for lesioning can be stopped when desired. The
      target we want to approach can be definitely and anatomically visualized and
      demonstrated, and the function of the target is evaluated with neurophysiologic
      impedance techniques and stimulation. Thus, if we are able to understand the
      language of the central nervous system, these are available, effective, and safe
      procedures in neurosurgical practice. We must remember that if intractable pain
      can be controlled by minimally invasive destructive techniques, the patients will
      not be dependent on implantable systems, drugs,and medical units. This
      independent lifestyle is a critical goal central to quality of life for patients
      having intractable pain.

PMID- 15246340
TI  - Treatment of trigeminal neuralgia.
AB  - When medical treatment for trigeminal neuralgia fails or is limited by
      significant side effects, neurosurgeons need to inform their patients of all the
      available treatment options. The best treatment for the patient depends on the
      age of the patient, medical comorbidities, and the risks the patient is willing
      to assume. We recommend microvascular decompression for younger healthy patients
      with a longer life expectancy. Percutaneous trigeminal neurolysis remains a
      useful minimally invasive approach for the older patient and for the patient with
      medical comorbidities and a shorter life expectancy. The role of stereotactic
      radiosurgery in the treatment of trigeminal neuralgia will be better defined in
      the future. Partial sectioning of the trigeminal nerve may be considered in
      patients who have negative explorations during a microvascular decompression or
      when other less invasive procedures have failed to provide adequate relief.

PMID- 15246341
TI  - Ablative procedures for chronic pain.
AB  - The advent of neuroaugmentative techniques has reduced the application of
      neuroablative procedures, especially as regards pain of functional origin.
      Although intracranial ablative procedures are now rarely performed, spinal
      ablative procedures, such as anterolateral cordotomies or midline myelotomies,
      remain important in the management of cancer pain. These procedures produce
      immediate and satisfactory pain relief with acceptable complication rates. An
      important future trend will be the application of radiosurgery guided by
      functional imaging (eg,fMRI, PET) to place such intracranial lesions as
      cingulotomies or medial thalamotomies.

PMID- 15246342
TI  - Deep brain stimulation for the treatment of chronic, intractable pain.
AB  - Deep brain stimulation (DBS) was first used for the treatment of pain in 1954.
      Since that time, remarkable advances have been made in the field of DBS, largely
      because of the resurgence of DBS for the treatment of movement disorders.
      Although DBS for pain has largely been supplanted by motor cortex and spinal cord
      stimulation during the last decade, no solid evidence exists that these
      alternative modalities truly offer improved outcomes. Furthermore, nuclei not yet
      fully explored are known to play a role in the transmission and modulation of
      pain. This article outlines the history of DBS for pain, pain classification,
      patient selection criteria, DBS target selection, surgical techniques,
      indications for DBS (versus ablative techniques), putative new DBS targets,
      complications, and the outcomes associated with DBS for pain.

PMID- 15246344
TI  - Acclimation of Haslea ostrearia to light of different spectral qualities -
      confirmation of 'chromatic adaptation' in diatoms.
AB  - The marine diatom Haslea ostrearia was cultured under light of different
      qualities, white (WL), blue (BL), green (GL), yellow (YL), red (RL), and far-red
      (FRL) and at two irradiance levels, low and high (20 and 100 micromolphotonsm(
      2)s(-1), respectively). The effects of the different light regimes were studied
      on growth, pigment content, and photosynthesis, estimated by the modulated
      fluorescence of chlorophyll, as relative electron transport rate (rETR). For all
      the light qualities studied, growth rates were higher at high irradiance.
      Compared to the corresponding WL controls, growth was higher in BL and lower in
      YL at low irradiance, and lower in YL and GL at high irradiance. Except for YL,
      almost all the pigment contents of the cells were lower at high irradiance. At
      low irradiance, cell pigment contents (chlorophyll a and c, fucoxanthin) and
      pigment ratios (in function of chlorophyll a) were lower in YL, RL, and FRL.
      Whatever the irradiance level, the maximum PSII quantum efficiency (F(v)/F(m)
      remained almost constant for WL, BL, and GL. Other fluorescence parameters
      (photochemical quenching, rETR(max), and alpha, the maximum light utilization
      coefficient) were lower in GL, YL, RL, and FRL, at low irradiance. Although not
      statistically significant, BL caused an increase in these fluorescence
      parameters. These findings are interpreted as evidence that inverse chromatic
      acclimation occurs in diatoms.

PMID- 15246345
TI  - A study of simultaneous photolysis and photoaddition reactions of riboflavin in
      aqueous solution.
AB  - The photodegradation reactions of riboflavin (RF) in the presence of 0.05-2.00 M
      phosphate (pH 7.0) have been studied using a specific multicomponent
      spectrophotometric method. The reactions involve simultaneous photolysis
      (intramolecular photoreduction) and photoaddition (intramolecular photoaddition)
      leading to lumichrome (LC) and cyclodehydroriboflavin (CDRF), respectively, as
      major products. The contribution of each reaction in the overall photodegradation
      depends upon the phosphate concentration, i.e., higher the phosphate
      concentration higher the extent of photoaddition. The apparent first-order rate
      constants for the photodegradation of RF and for the formation of LC and CDRF at
      0.25-2.00 M phosphate concentration range from 0.65 to 3.03 x 10(-2), and from
      0.41 to 0.99 x 10(-2) and 0.12 to 1.63 x 10(-2) min(-1), respectively. The second
      order rate constants for the phosphate catalysed photodegradation of RF and for
      the formation of LC and CDRF are 2.12 x 10(-4) and 0.61 x 10(-4) and 1.41 x 10(
      4) M(-1)s (-1), respectively. Since the formation of CDRF by photoaddition is
      catalysed by HPO(4)(2-) ions, it is suggested that H(2)PO(4)(-) ions may be
      involved in the formation of LC by photolysis. Thus, both H(2)PO(4)(-) and
      HPO(4)(2-) ions may catalyse the two major reaction pathways of riboflavin
      photodegradation, respectively.

PMID- 15246346
TI  - delta-Aminolaevulinic acid mediated photodynamic antimicrobial chemotherapy on
      Pseudomonas aeruginosa planktonic and biofilm cultures.
AB  - To demonstrate photodynamic antimicrobial chemotherapy (PACT) against planktonic
      and biofilm cultures of Pseudomonas aeruginosa, using photoporphyrin IX which
      could be endogenously synthesized by administrating delta-aminolaevulinic acid
      (delta-ALA), and a light emitted diode (LED) array to photoactivate the
      photosensitizer. P. aeruginosa suspended cells or biofilms, grown on a rotating
      disk reactor, were treated by different concentrations of delta-ALA in the dark
      for 1 h, followed by LED irradiation for various time. Regrowth experiments were
      conducted by placed PACT-treated disks back to a sterile reactor. Viable cells
      were determined by serial dilution and plate counts. Both P. aeruginosa
      planktonic and biofilm cells were inhibited by PACT with light doses or
      photosensitizer concentrations increasing. Treatments of planktonic cells with 10
      mM delta-ALA and incident dose 240 J cm(-2) or 7.5 mM ALA and incident dose 360 J
      cm(-2) led to completely photoinactivation. No viable biofilm cells were found
      after treatment of 20 mM delta-ALA and incident dose 240 J cm(-2). However,
      regrowth was observed once PACT-treated biofilms were put back to a sterile
      reactor. Regrowth could be prevented only if biofilm samples were treated PACT
      twice. delta-ALA-mediated PACT on P. aeruginosa planktonic and biofilm cells was
      effective, though the detailed mechanism still required further investigation.

PMID- 15246347
TI  - Cytotoxicity of nitroheterocyclic compounds, quinifuryl and nitracrine, towards
      leukaemic and normal cells on the dark and under illumination with visible light.
AB  - The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro
      9(3-3-dimethylaminopropylamino) acridine and Quinifuryl, 2-(5'-nitro-2'-furanyl)
      ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline, towards
      two lines of leukaemic cells and a line of non-transformed cells, was measured in
      comparison, on the dark and under illumination with visible light (350-450 nm).
      Both drugs showed highly elevated cytotoxicity when illuminated with LC(50)
      values 7-35 times lower after 1 h illumination compared to 1 h incubation of
      cells incubation with drug on the dark. Cytotoxicity of Nitracrine toward all
      cell lines studied exceeded that of Quinifuryl, both on the dark and under
      illumination, so that approximately 10 times lower concentration of former drug
      was needed to reach the same toxicity as the latter. General toxic effect was
      calculated as a direct cell kill and a cell proliferation arrest. The effect >80%
      for both drugs was achieved after 1 h cell illumination with as low drug
      concentrations as 0.2 microM for Quinifuryl and 0.02 microM for Nitracrine.

PMID- 15246348
TI  - Effect of growth phase on the Escherichia coli response to ultraviolet-A
      radiation: influence of conditioned media, hydrogen peroxide and acetate.
AB  - The results reported herein indicate that the ultraviolet-A (UVA) radiation
      induced effects in Escherichia coli depend on its growth phase. Stationary-phase
      cells recover faster from a sub-lethal UVA exposure and have a higher resistance
      to lethal effect of the radiation than exponential growing cells. Although pre
      incubation in spent medium supernatant increased the resistance of log-phase
      cells to lethal UVA effects, this pre-treatment considerably prolonged the
      duration of the radioinduced sub-lethal growth delay. The aim of the present
      study was to investigate the effect exerted by the E. coli conditioned media and
      evaluate the influence of nutritional stress, hydrogen peroxide and acetate. Pre
      incubated in conditioned medium, cells in exponential growth phase were
      irradiated and the induced effects were compared with those found when catalase,
      high culture densities and acetate were employed. Unexpectedly, the duration of
      the growth delay in cells submitted to these treatments was shortened in
      comparison with control cells incubated in conditioned medium with no
      modifications. Lengthening of the growth delay was mimicked when exponentially
      growing cells were incubated in fresh medium supplied with 5 microM H(2)O(2). The
      effects of spent medium on wild type and rpoS mutant strains were similar,
      indicating that this response is independent of RpoS controlled functions. We
      assumed that an oxidative component of the spent medium, probably H(2)O(2), could
      be involved in the observed phenomenon. This effect is specific of E. coli and
      independent of rpoS.

PMID- 15246349
TI  - Regulation of the excitation energy utilization in the photosynthetic apparatus
      of chlorina f2 barley mutant grown under different irradiances.
AB  - Acclimation of the photosynthetic apparatus of chlorophyll b-less barley mutant
      chlorina f2 to low light (100 micromolm(-2)s(-1); LL) and extremely high light
      level (1000 micromolm(-2)s(-1); HL) was examined using techniques of pigment
      analysis and chlorophyll a fluorescence measurements at room temperature and at
      77 K. The absence of chlorophyll b in LL-grown chlorina f2 resulted in the
      reduction of functional antenna size of both photosystem II (by 67%) and
      photosystem I (by 21%). Chlorophyll fluorescence characteristics of the LL-grown
      mutant indicated no impairment of the utilization of absorbed light energy in
      photosystem II photochemistry. Thermal dissipation of excitation energy estimated
      as non-photochemical quenching of minimal fluorescence (SV(0)) was significantly
      higher as compared to the wild-type barley grown under LL. Despite impaired
      assembly of pigment-protein complexes, chlorina f2 was able to efficiently
      acclimate to HL. In comparison with chlorina f2 grown under LL, HL-grown chlorina
      f2 was characterized by unaffected maximal photochemical efficiency of
      photosystem II (F(V)/F(M), doubled content of both beta-carotene and the
      xanthophyll cycle pigments and considerably reduced efficiency of excitation
      energy transfer from carotenoids to chlorophyll a. The enormous xanthophyll cycle
      pool size was however associated with reduced SV(0) capacity. We suggest that the
      substantial part of the xanthophyll cycle pigments is not bound to the remaining
      pigment-protein complexes and acts as filter for excitation energy, thereby
      contributing to the efficient photoprotection of chlorina f2 grown under HL.

PMID- 15246350
TI  - A polarity dependent fluorescence "switch" in live cells.
AB  - The spectroscopic properties, ultrafast kinetics and utilization of a
      photochromic molecule as a bi-stable fluorescing sensor of polarity in live cells
      are described. This molecule is a photochromic fulgimide, 2,3
      dialkylidenesuccinimide, which emits fluorescence that can be switched optically
      on and off. The fluorescence intensity is a function of the polarity of the
      molecular environment, namely it fluoresces strongly when the molecule is in its
      polar isomeric structure form. We demonstrate that this molecule enters live
      cells without inducing damage, it binds primarily to internal membranous
      organelles (mitochondria) and its fluorescence can be switched optically "on" and
      "off" repeatedly while inside the living cell. A possible use as a bi-stable,
      on/off sensor is discussed.

PMID- 15246351
TI  - The use of comet assay data with a simple reaction mechanism to evaluate the
      relative effectiveness of free radical scavenging by quercetin, epigallocatechin
      gallate and N-acetylcysteine in UV-irradiated MRC5 lung fibroblasts.
AB  - Comet assay data (tail DNA %) have been gathered for the concentration dependent
      role of three antioxidants (AOs); quercetin (Q), epigallocatechin gallate (EGCG)
      and N-acetylcysteine (NAC) in reducing UV-induced damage to DNA in normal fetal
      lung fibroblasts (MRC5). All three compounds demonstrate a concentration
      dependent reduction maximum with a pro-oxidant effect at higher (though not
      cytotoxic) concentrations. Manipulation of a simple 4-step reaction mechanism for
      free radical (FR) scavenging by AOs produced rate constant ratios which allowed
      the relative effectiveness (Q > EGCG > NAC) of the AOs to be evaluated.

PMID- 15246352
TI  - Dynamics of potentially protective compounds in Rhodophyta species from Patagonia
      (Argentina) exposed to solar radiation.
AB  - The impact of solar radiation upon potentially protective compounds (i.e., UV
      absorbing compounds and carotenoids) was assessed in four Rhodophyte species from
      Patagonia (i.e., Ceramium sp. Lyngbye, Corallina officinalis Linnaeus,
      Callithamnion gaudichaudii Agardh and Porphyra columbina Montagne) during short
      term (i.e., 46 h) experiments. Algae were exposed to solar radiation under two
      treatments (PAR only: 400-700 nm, and PAR+UVR: 280-700 nm) and sub-samples were
      taken every 3 h (or longer periods at night) to determine the spectral absorption
      characteristics and concentration of UV-absorbing compounds, carotenoids and
      photosynthetic pigments. Except for C. gaudichaudii which displayed a decrease in
      chl-a concentration throughout the experiment, photosynthetic pigments had small
      variations in all species. UV-absorbing compounds concentration had species
      specific responses: Ceramium sp. was the only species in which UV-absorbing
      compounds concentration varied as a function of solar irradiance, with maximum
      values around local noon. In C. officinalis and P. columbina UV-absorbing
      compounds concentration increased as compared to that of chl-a; in Ceramium sp.
      and C. gaudichaudii, however, there was no relationship between UV-absorbing
      compounds content and chl-a concentration. Carotenoids, on the other hand, did co
      vary with chl-a in all species. Our data suggest that, with the exception of C.
      gaudichaudii, the differential responses of UV-absorbing compounds concentrations
      are more associated to the previous light history of the algae (i.e., in turn due
      to their position in the intertidal zone) rather than to the radiation treatment
      imposed to the samples. Based on our results, the variable impact of solar
      radiation upon productivity (and eventually biodiversity) of macroalgae from
      Patagonia might consequently differentially affect higher trophic levels of the
      aquatic food web.

PMID- 15246353
TI  - Protochlorophyllide phototransformation in the bundle sheath cells of Zea mays.
AB  - The protochlorophyllide transformation process was investigated by using
      comparative analysis of 77 K fluorescence spectral changes occurring in isolated
      bundle sheath (BS) cells of etiolated Zea mays leaves after being exposed to a
      200 ms saturating flash. Deconvolution analysis of the fluorescence spectra
      showed essential differences in the ratio of protochlorophyll(ides) and
      chlorophyll(ides) spectral forms indicating for BS cells to have a characteristic
      pathway of protochlorophyllide transformation. Bundle sheath cells showed a high
      ratio between non-photoactive protochlorophyll(ide)-F632 and photoactive
      protochlorophyllide-F655. In those cells, the 200 ms flash triggered a
      preferential formation of chlorophyll(ide)-F675 which remained stable in the dark
      for at least 90 min. Isolated BS cells showed an accumulation of chlorophyll(ide)
      F675 resulting in the formation of inactive photosystem II. However for mesophyll
      cells of intact leaves, it was found to have a high ratio between photoactive and
      non-photoactive protochlorophyll(ide), showing the succession of chlorophyll(ide)
      forms usually known in C(3) plants. Protochlorophyllide phototransformation
      pathway in BS cells related to early stages of plastid differentiation triggered
      by light may indicate specific conditions for PSII assembly process leading to
      inactive PSII forms.

PMID- 15246354
TI  - Distribution of metal-free sulfonated phthalocyanine in subcutaneously
      transplanted murine tumors.
AB  - Metal-free sulfonated phthalocyanine with the average number of sulfonate groups
      per molecule 2.4 (H(2)PcS(2.4)) was recently proved to be an efficient
      photosensitizer for the photodynamic therapy. Fluorescence spectral imaging
      microscopy was applied here to study localization and relative concentration of
      H(2)PcS(2.4) with micron-scale resolution in subcutaneously transplanted murine
      tumors: Ehrlich mammary gland carcinoma (EC), Lewis lung carcinoma (LLC), P388
      lymphoid leukemia (P388) and B16 melanoma (B16). The study of cryogenic tissue
      sections prepared 24 h after H(2)PcS(2.4) intravenous injection revealed that
      H(2)PcS(2.4) was present in all tissue structures in the monomeric photoactive
      state. The preferential accumulation of H(2)PcS(2.4) was documented in tumor
      cells and adjacent non-tumor tissues (skin structures, fatty tissue, connective
      tissue enriched in fibrous component and infiltrated with fibroblasts and
      macrophages) for all the studied tumor models. P388 and B16 were stained with
      H(2)PcS(2.4) less than adjacent skin structures, whereas EC and LLC accumulated
      H(2)PcS(2.4) alike or higher than particular skin structures. Staining of EC and
      LLC was similar and ca. 1.4 and 2 times higher than that of B16 and P388,
      respectively, thus revealing the differences in ability of particular tumor
      strains to H(2)PcS(2.4) accumulation. The H(2)PcS(2.4) concentration in remote
      healthy tissues (skin, muscles and connective tissue) was 2-3 times lower as
      compared with the analogous tissue structures from the tumor area, whereas
      subcutaneous fatty tissue staining did not depend on the tissue-to-tumor
      distance. The tissue distribution of H(2)PcS(2.4) predefines the combined action
      of two photodynamic damage mechanisms: eradication of tumor due to the direct
      tumor cell destruction and suppression of tumor growth due to the injury of
      growth supporting system.

PMID- 15246355
TI  - Comparison between chlorosomes containing bacteriochlorophyll-c and chlorosomes
      containing bacteriochlorophyll-d isolated from two substrains of green sulfur
      photosynthetic bacterium Chlorobium vibrioforme NCIB 8327.
AB  - Chlorosomes containing bacteriochlorophyll(BChl)-c and those containing BChl-d
      were isolated from two substrains of Chlorobium vibrioforme f. sp.
      thiosulfatophilum NCIB 8327, respectively. The two types of chlorosomes were
      investigated from the following aspect, what kinds of effects the molecular
      structure of chlorosomal BChls had on structural and spectroscopic properties of
      in vivo self-aggregates in chlorosomes without alteration of the other components
      such as chlorosomal proteins and lipids; both chlorosomes were expected to have
      the same components except for light-harvesting BChls. In their visible
      absorption spectra, the differences of Soret and Q(y) peak positions between BChl
      c containing and BChl-d containing chlorosomes were similar to the differences
      between monomeric BChl-c and d. An inverse S-shaped CD signal in the Q(y) region
      of BChl-d containing chlorosomes was 1.4 times larger than that of BChl-c
      containing chlorosomes, when the Q(y) absorbance of the two chlorosomes was
      almost the same. This implies that the excitonic interaction of BChl-d is larger
      than that of BChl-c in natural chlorosomes. Resonance Raman spectroscopy showed
      that BChl self-assemblies in both chlorosomes were essentially formed by the same
      local structural interaction among 3(1)-hydroxy group, 13-keto group, and central
      magnesium. BChl-d self-aggregates in chlorosomes were more tolerant of 1-hexanol
      than in vivo BChl-c aggregates, suggesting that the molecular structure of BChl-d
      provided more stable self-assemblies than BChl-c in natural chlorosomes.

PMID- 15246356
TI  - Enhancement of the photoluminescence of CdSe quantum dots during long-term UV
      irradiation: privilege or fault in life science research?
AB  - The present study describes an impressive enhancement of the photoluminescence
      (PL) intensity of low-temperature synthesized CdSe nanocrystals (75 degrees C)
      during long-term UV-irradiation. The integrated PL-intensity of CdSe core and
      CdSe/ZnS core/shell nanocrystals, dispersed in chloroform, enhanced about 3 and 6
      times, respectively, during 9 h exposure to UV-light, without any significant
      changes in the characteristic absorbance spectra and shifting of PL-spectra.
      After termination of the irradiation a comparatively slow photobleaching was
      detected with tau(1/2) = 6 h for CdSe core and tau(1/2) = 14 h for CdSe/ZnS
      core/shell nanocrystals. The most impressive was the effect of UV-irradiation on
      the photoluminescence of water-soluble CdSe nanocrystals. The integrated PL
      intensity enhanced about 10 times during 11 h exposure to UV-light and the
      improved PL-intensity was preserved during 3 days after termination of the
      irradiation without any significant photobleaching. The results are discussed in
      the context of application of CdSe nanocrystals as novel fluorophores in life
      science experiments.

PMID- 15246357
TI  - Spectroscopic evidence of monomeric aluminium phthalocyanine tetrasulphonate in
      aqueous solutions.
AB  - Aqueous solutions of aluminium phthalocyanine tetrasulphonate (AlPcS(4)) were
      investigated by means of absorption and fluorescence spectroscopy. The absorption
      spectrum of AlPcS(4) is independent of concentration in a wide range (from 10(-8)
      to 10(-4) M). The fluorescence spectrum measured with a standard setup is
      strongly dependent on AlPcS(4) concentration, and the fluorescence maximum is
      gradually red-shifted with increasing concentration. Calculations that take into
      account reabsorption of fluorescence (inner-filter effect) fit the experimental
      observations at low concentrations (up to 10(-6) M). Disagreement between the
      calculations and spectra recorded at higher concentrations (above 10(-5) M) shows
      that the reabsorbed light may be reemitted as fluorescence. The influence of
      inner-filter effects on the spectral shape was demonstrated by the experiments
      where a fibre-optic front-face fluorescence setup was applied: Under such
      conditions the shape of the fluorescence spectra for a high concentration (10(-3)
      M) coincided with that of a low concentration (10(-8) M). In conclusion, the
      present spectroscopic results show that AlPcS(4) does not form aggregates and is
      a very stable compound in aqueous solutions.

PMID- 15246358
TI  - Influence of farnesyl transferase inhibitor treatment on epidermal growth factor
      receptor status.
AB  - The radiolabelled growth factor [(123/125)I] I-hEGF is evaluated in vitro and in
      vivo to monitor the acute effects on the EGFR of R115777, a farnesyl transferase
      inhibitor (FTI). Upregulation of the EGFR after incubation with R115777
      correlated linearly with FTI induced acute growth inhibition. Receptor mediated
      [125I] I-hEGF internalization decreased following R115777 treatment. Preliminary
      data suggest that the net in vivo effect is a decrease of [123I] I-hEGF uptake in
      the tumour. These findings suggest the possible use of radioiodinated hEGF as a
      radiodiagnosticum to investigate EGFR status changes as a predictor for eventual
      FTI chemotherapy outcome in vivo.

PMID- 15246359
TI  - Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine
      substitution at the 16alpha-position of fulvestrant (faslodex; ICI 182,780).
AB  - Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist
      recently approved for the treatment of hormone-sensitive breast cancer in post
      menopausal women with disease progression following antiestrogen therapy.
      Fulvestrant strongly binds to the ER and its mode of action consists of
      inhibition of ER dimerization leading to a down regulation of ER protein cellular
      levels. With the aim to develop a probe for positron emission tomography (PET)
      imaging capable of predicting the potential therapeutic efficacy of selective ER
      modulators (SERM), we prepared three new 16alpha-[18F]fluoro-fulvestrant
      derivatives. These new radiopharmaceuticals were evaluated for their binding
      affinity to the human ERalpha and for their target tissue uptake in immature
      female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18F
      would have led to a product of low specific activity; instead we selected the
      16alpha-position for 18F-labeling, which at least in the case of estradiol (ES)
      is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective
      introduction of the [18F]fluoride at the 16-18F-position of fulvestrant via
      opening of an intermediate O-cyclic sulfate followed by hydrolysis of the
      protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with
      different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or
      sulfoxide (fulvestrant) were prepared. Introduction of the 16(18)F-fluorine led
      to a dramatic decrease of the apparent binding affinity for ER, as reported by
      Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated
      uterus uptake values in immature female rats were disappointing. Overall, our
      findings suggest that these new PET radiopharmaceuticals are not suitable as
      tracers to predict ER(+) breast cancer response to hormonal therapy with
      selective ER modulators.

PMID- 15246360
TI  - PET evaluation of the uptake of N-[11C]methyl CP-643,051, an NK1 receptor
      antagonist, in the living porcine brain.
AB  - Antagonists of neurokinin receptors such as CP-643,051 are presently under
      investigation as potential antidepressants, but little is known about the brain
      uptake and distribution of these agents. We developed a method for the efficient
      N-[11C]methylation of CP-122,721, yielding the NK1 antagonist N-[11C]methyl CP
      643,051. The brain uptake and distribution of N-[11C]methyl CP-643,051 were
      studied by positron emission tomography (PET) in the anaesthetized pig, first in
      a baseline condition, and again after displacement of specific binding with the
      NK1 receptor antagonist L-732,138 (0.6 mg/kg, i.v.). In order to validate this
      displacement procedure, we tested the effects of L-732,138 on cerebral blood flow
      (CBF) in one pig. We found that N-[11C]methyl CP-643,051 had a distribution
      volume close to 3 ml g(-1), and a binding potential (pB) of 0.3 in the pig
      striatum; this binding was displaceable by the L-732,138 pre-treatment, which
      evoked a small (10-20%) global increase in CBF. We conclude that of N-[11C]methyl
      CP-643,051 may serve as a lead structure for the development of PET NK-1 ligands
      of higher specific binding in vivo.

PMID- 15246361
TI  - Synthesis and biological evaluation of [11C]talopram and [11C]talsupram:
      candidate PET ligands for the norepinephrine transporter.
AB  - PET and SPECT ligands for the norepinephrine transporter (NET) will be important
      tools for studying the physiology, pathophysiology and pharmacology of the CNS
      noradrenergic system in vivo. A series of candidate NET ligands were synthesized
      and characterized in terms of their affinity for human monoamine transporters.
      The two most promising compounds, talopram and talsupram, were radiolabeled with
      carbon-11 and evaluated through biodistribution studies in rats and PET imaging
      studies in a rhesus monkey. Although both compounds displayed high affinity and
      selectivity for the human NET in vitro, these compounds did not enter the CNS in
      adequate amounts to be used in PET imaging studies.

PMID- 15246362
TI  - In vivo tracking of implanted stem cells using radio-labeled transferrin
      scintigraphy.
AB  - The possibility of monitoring stem cells in vivo with radionuclide imaging after
      transplantation was investigated. Based on the results of a radioligand receptors
      assay that human mesenchymal stem cells (hMSCs) express a high level of
      transferrin receptors, iodinated transferrin (131I-Tf(Fe)2) was chosen as the
      radiotracer for imaging the cells implanted into the spinal cords of rabbits.
      Accumulation of radioactivity at the cell transplanted sites was assessed 16 and
      24 hours post-intrathecal injection of 131I-Tf(Fe)2. Transferrin receptors
      expression and Tf binding of the implanted cells were verified by
      immunofluorescence and ex vivo phosphor imaging. The specificity of Tf uptake of
      hMSCs was proved through control experiments, i.e., replacing 131I-Tf(Fe)2 with
      131I labeled human serum albumin as the tracer or substituting hMSCs with
      phosphate buffered saline as the grafts. Despite some defects, such as the
      invasive administration of the tracer and the non-specificity of transferrin
      receptors as a marker of stem cells in this preliminary study, the technique of
      nuclear medicine imaging is considered to have great potential in tracking
      implanted cells in vivo.

PMID- 15246363
TI  - A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the
      serotonin transporter ligand [11C]2-[2-dimethylaminomethylphenylthio)]-5
      fluorophenylamine ([11C]AFA).
AB  - A new serotonin transporter (SERT) ligand, [11C]2-[2
      (dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [11C]AFA), was
      synthesized and evaluated as a candidate PET radioligand in pharmacological and
      pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either
      C-11 or F-18. In vitro, AFA displayed high affinity for SERT (Ki 1.46 +/- 0.15
      nM) and lower affinity for norepinephrine transporter (NET, Ki 141.7 +/- 47.4 nM)
      or dopamine transporter (DAT, Ki > 10,000 nM). [11C]AFA (10) was prepared from
      its monomethylamino precursor 9 by reaction with high specific activity
      [11C]methyl iodide. Radiochemical yield was 43 +/- 20% based on [11C]methyl
      iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 +/-
      1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats
      indicated that [11C]AFA accumulated in brain regions known to contain high
      concentrations of SERT. Binding in SERT-rich brain regions was reduced
      significantly by pretreatment with either the cold compound 8 or with the
      selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the
      selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in
      vivo binding selectivity and specificity for SERT. Imaging experiments in baboons
      demonstrated that the uptake pattern of [11C]AFA in the baboon brain is
      consistent with the known distribution of SERT, with highest activity levels in
      the midbrain and thalamus, followed by striatum, hippocampus, and cortical
      regions. Activity levels in the baboon brain peaked at 15-40 min after
      radioligand injection, indicating a fast uptake kinetics for [11C]AFA.
      Pretreatment of the baboon with citalopram (4 mg/kg) significantly reduced the
      specific binding of [11C]AFA in all SERT-containing brain regions. Kinetic
      analysis revealed that the regional equilibrium specific to non-specific
      partition coefficients (V3") of [11C]AFA are similar to those of [11C]McN5652,
      but lower than those of [11C]AFM or [11C]DASB. In summary, [11C]AFA appears to be
      an appropriate PET radioligand with a fast brain uptake kinetics:

PMID- 15246364
TI  - Synthesis, radiosynthesis, and in vitro characterization of [125I]-2- iodo-L
      phenylalanine in a R1M rhabdomyosarcoma cell model as a new potential tumor
      tracer for SPECT.
AB  - [125I]-2-iodo-L-phenylalanine, a new radioiodinated phenylalanine analog was
      evaluated as a potential specific tumor tracer for SPECT. The tracer is obtained
      with an overall radiochemical yield of at least 98%, a purity of > 99%, and a
      specific activity of 11 MBq/mmol in one pot Kit conditions using the Cu1+
      assisted isotopic exchange. The tracer is evaluated in vitro using R1M rat
      rabdomyosarcoma cells in HEPES buffer with and without Na+ ions and in MEM
      buffer. The uptake of [125I]-2-iodo-L-phenylalanine follows a reversible pseudo
      first-order reaction which is the same in presence and absence of Na+ ions, but
      the compound is not incorporated into the cell proteins. The reversible uptake is
      proven to occur with the same affinity as L-henylalanine by a saturable transport
      system which is competitively inhibited by BCH, an L transport type selective
      molecule. Trans-stimulation of the efflux by BCH and typical L transported amino
      acids shows that the transporter is of the antiport type and fulfils all the
      properties of the LAT1 heterodimer transport system. [125I]-2-iodo-L
      phenylalanine is thus a phenylalanine analog that for the uptake uses for the
      major part the LAT1 transport system which is known to be over-expressed in tumor
      cells. This, together with the easy Kit preparation, makes [123I]-2-iodo-L
      phenylalanine a promising tumor specific tracer for SPECT.

PMID- 15246366
TI  - 177Lu-DOTA-lanreotide: a novel tracer as a targeted agent for tumor therapy.
AB  - 177Lu of specific activity approximately 100-110 TBq/g and radionuclidic purity
      of approximately 100% was obtained by irradiation of enriched Lu2O3 (60.6% 176Lu)
      target for 7 days at a thermal neutron flux of 3 x 10(13)n/cm2/sec. The 177Lu
      labeling of a macrocyclic bifunctional chelating agent viz. 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has been extensively
      studied. Lanreotide, [beta-naphthyl-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2] a
      disulfide-linked cyclic octapeptide and a somatostatin analog, reported to bind
      with a wide variety of tumors expressing somatostatin receptors, was conjugated
      with DOTA. The peptide-BFCA conjugate was characterized with the help of high
      resolution two-dimensional proton NMR spectroscopy. The 177Lu labeling of the
      DOTA-lanreotide conjugate has been standardized to give a radiolabeling yield of
      85%. The tracer showed specific binding with A-431 human epidermoid carcinoma and
      IMR-32 human brain neuroblastoma cells.

PMID- 15246365
TI  - Preparation of F-18 labeled annexin V: a potential PET radiopharmaceutical for
      imaging cell death.
AB  - The clinical response to antitumor therapy is measured using imaging, such as CT
      or MRI, 6-12 weeks following chemotherapy treatment. The images at that time
      reflect both tumor cell death and new growth. Therefore, the amount of tumor cell
      death caused by chemotherapy cannot be efficiently quantified with current
      imaging modalities. A quantitative measurement of tumor cell death immediately
      following chemotherapy is needed to help validate both new agents and to optimize
      administration of existing therapies. Annexin V is a 36kD protein that binds to
      exposed phosphatidylserine (PS) on dying cells. In order to synthesize a probe
      that can detect cell death in vivo, the positron emitter F-18 was conjugated to
      annexin V via the compound N- succinimidyl-4-[18F]fluorobenzoate, [18F]SFB. The
      decay corrected radiochemical yield of F-18 labeled annexin V from 18F fluoride
      was 17.6 +/- 5.6% (n = 4) in three hours. The stepwise radiochemical yield of the
      conjugation step with annexin V was as high as 70% when a protein concentration
      of 5 mg/ml was used. Cancer cells treated with the chemotherapeutic agent,
      etoposide, showed an 88% increase in the binding of F-18 labeled annexin V
      compared to untreated cells. We conclude that [18F] labeled annexin V can be
      readily prepared by the conjugation of annexin V with [18F]SFB and that the
      positron-emitting compound is biologically active in detecting apoptosis.

PMID- 15246367
TI  - Breast cancer models to study the expression of estrogen receptors with small
      animal PET imaging.
AB  - Different animal models of estrogen positive tumors (ER+) were evaluated for
      their suitability to follow tumor response after various treatment protocols,
      using small animal positron emission tomography (PET). ER+ human breast cancer
      cell lines MCF-7 and T-47D, using MDA-MB-231 as ER-; control, and murine mammary
      ductal carcinomas MC4-L2, MC4-L3, and MC7-L1, were compared for their in vivo
      growth rate and retention of ER+ status. Tumor metabolic activity was estimated
      from the relative uptake (% injected dose/g) of [18F]fluorodeoxyglucose (FDG)
      uptake, whereas ER content was determined from 16alpha-[18F]fluoroestradiol (FES)
      retention. F-18 activity values were obtained by small animal PET imaging and
      confirmed by tissue sampling and radioactivity counting. Reliable uptake
      measurements could be obtained for tumors of 200 microl or over. The human cell
      lines grew at a slower rate in vivo and failed to accumulate FES; in contrast,
      the Balb/c MC7-L1 and MC4-L2 grew well and showed good uptake of both FDG and
      FES. Chemotherapy and hormone therapy delayed the growth of MC7-L1 and MC4-L2
      tumors, confirming their suitability as an ER+ model for therapeutic
      interventions. MC4-L3 tumors also showed promising results but required the
      presence of progestative pellets to grow. These data demonstrate that murine MC7
      L1 and MC4-L2 tumors are suitable models for the monitoring of ER+ breast cancer
      therapy using small animal PET imaging.

PMID- 15246368
TI  - Experiment assessment of mass effects in the rat: implications for small animal
      PET imaging.
AB  - In vivo imaging using positron emission tomography (PET) is important in the
      development of new radiopharmaceuticals in rodent animal models for use as
      biochemical probes, diagnostic agents, or in drug development. We have shown
      mathematically that, if small animal imaging studies in rodents are to have the
      same "quality" as human PET studies, the same number of coincidence events must
      be detected from a typical rodent imaging "voxel" as from the human imaging
      voxel. To achieve this using the same specific activity preparation, we show that
      roughly the same total amount of radiopharmaceutical must be given to a rodent as
      to a human subject. At high specific activities, the mass associated with human
      doses, when administered to a rodent, may not decrease the uptake of
      radioactivity at non saturable sites or sites where an enzyme has a high capacity
      for a substrate. However, in the case of binding sites of low density such as
      receptors, the increased mass injected could saturate the receptor and lead to
      physiologic effects and non-linear kinetics. Because of the importance of the
      mass injected for small animal PET imaging, we experimentally compared high and
      low mass preparations using ex vivo biodistribution and phosphorimaging of three
      compounds: 2-fluoro-2-deoxyglucose (FDG), 6-fluoro-L-metatyrosine (FMT) and one
      receptor-directed compound, the serotonin 5HT1A receptor ligand, trans-4-fluoro-N
      [2-[4-(2-methoxylphenyl) piperazino]ethyl]-N-(2-pyridyl) cyclohexane- carboxamide
      (FCWAY). Changes in the mass injected per rat did not affect the distribution of
      FDG, FMT, and FCWAY in the range of 0.6-1.9 nmol per rat. Changes in the target
      to nontarget ratio were observed for injected masses of FCWAY in the range of
      approximately 5-50 nmol per rat. If the specific activity of such compounds
      and/or the sensitivity of small animal scanners are not increased relative to
      human studies, small animal PET imaging will not correctly portray the "true"
      tracer distribution. These difficulties will only be exacerbated in animals
      smaller than the rat, e.g., mice.

PMID- 15246369
TI  - Monitoring the effect of PEGylation on polyethylenimine in vivo using nuclear
      imaging technique.
AB  - Polyethyleneimine (PEI) has been extensively investigated for use as a nonviral
      gene delivery vector due to its "proton sponge" mechanism. This work monitored
      the effect of PEGylation in vivo using nuclear imaging technique. We synthesized
      galactosylated PEI-PEG with different levels of PEG substitution ranging from 4.1
      to 13.3 mol% of PEI amino groups. Validation of the differences of the in vivo
      distribution in the varying degrees of PEG substitution was performed using
      nuclear imaging with a gamma camera. PEGylated PEIs could easily label with
      reduced 99mTc because of their interaction with PEI amino groups. After systemic
      administration of 99mTc PEGylated Gal-PEIs, rapid accumulation in the liver,
      spleen, and lung was observed. However, with increasing amounts of PEG, the lung
      uptake was markedly reduced. These results demonstrate that nuclear imaging
      technique may be used as a basic screening tool for determining the optimized
      system of PEGylated Gal-PEIs. Once optimized, this system could be used as a
      hepatocyte targeted non-viral gene delivery vector which minimizes unspecific
      interactions with cellular blood components such as vessel endothelia and plasma
      proteins.

PMID- 15246370
TI  - Synthesis and biological evaluation of silylated mixed-ligand 99mTc complexes
      with the [PNS/S] donor atom set.
AB  - New oxotechnetium complexes of general formula [99mTc(O)(PNS)(S(CH2)nOSiR3)] (4
      6) were synthesized by direct reduction of [99mTcO4]- with stannous chloride, in
      the presence of the tridentate heterofunctionalized phosphine H2PNS and of the
      monodentate silylated thiols [HS(CH2)nOSiR3] (n = 2, R = Ph (1); n = 3, R = Ph
      (2); n = 3, R = Et (3)). The mixed-ligand rhenium and technetium complexes of
      general formula [M(O)(PNS)(S(CH2)nOH)] (n = 2: M = 99mTc, (7), M = Re, (7a); n =
      3: M = 99mTc, (8), M = Re, (8a)) were also prepared. All the 99mTc complexes were
      obtained with high radiochemical purity (> 95%), after purification by HPLC, and
      were characterized by comparison of their HPLC profiles with the ones obtained
      for the corresponding Re compounds. The silylated compounds 4-6 are stable in
      phosphate saline buffer (PBS) pH 7.4, rat plasma, human serum and whole blood,
      and do not bind to plasmatic proteins, and also do not challenge with
      glutathione. The biological behavior of [99mTc(O)(PNS)(S(CH2)nOH)] (7, 8) and
      [99mTc(O)(PNS)(S(CH2)nOSiR3)] (4-6) was studied. The effect of the pH on the
      cleavage of the O-Si bond in complexes 4-6 was also evaluated.

PMID- 15246372
TI  - Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine.
AB  - We developed a new fully automated method for the synthesis of 3'-deoxy-3'
      [18F]fluorothymidine ([18F]FLT), by modifying a commercial FDG synthesizer and
      its disposable fluid pathway. Optimal labeling condition was that 40 mg of
      precursor in acetonitrile (2 mL) was heated at 150 degrees C for 100 sec,
      followed by heating at 85 degrees C for 450 sec and hydrolysis with 1 N HCl at
      105 degrees C for 300 sec. Using 3.7 GBq of [18F]F- as starting activity,
      [18F]FLT was obtained with a yield of 50.5 +/- 5.2% (n = 28, decay corrected)
      within 60.0 +/- 5.4 min including HPLC purification. With 37.0 GBq, we obtained
      48.7 +/- 5.6% (n = 10). The [18F]FLT showed the good stability for 6 h. This new
      automated synthesis procedure combines high and reproducible yields with the
      benefits of a disposable cassette system.

PMID- 15246371
TI  - Development of a spectroscopic assay for bifunctional ligand-protein conjugates
      based on copper.
AB  - A simple, non-radioactive method for the determination of ligand-to-protein ratio
      (L/P) for novel ligand-antibody conjugates has been developed based on an
      exchange equilibrium with the purple Cu(II) complex of arsenazo III. The method
      requires a UV/Vis spectrometer and has been verified for monoclonal antibody
      Herceptin conjugates of a variety of ligand modalities, including common
      macrocyclic compounds NOTA and TETA, and with a new bifunctional tachpyridine (1H
      Pyrrole-1-butanamide,N-[4-[[(1alpha,3alpha,5alpha)-3,5-bis[(2
      pyridinylmethyl)amino]cyclohexyl](2-pyridinylmethyl)amino]butyl]-2,5-dihydro-2,5
      dioxo-(9CI)). The spectroscopically derived values for L/P were verified by
      titration of the ligand-antibody conjugate with 64Cu. In each case, the value
      obtained by UV/Vis spectroscopy matches that found by radiolabeling. The method
      is rapid, taking less than 30 minutes with each ligand in this study.

PMID- 15246373
TI  - Availability of N-isopropyl-p-[125I]iodoamphetamine (IMP) as a practical cerebral
      blood flow (CBF) indicator in rats.
AB  - Since a very complicated technique is necessary to measure cerebral blood flow
      (CBF) with [14C]iodoantipyrine in small animals, a practical and easy method is
      needed. In this paper, the differential uptake ratio (DUR) at 5 min after
      injection of N-isopropyl-p-[125I]iodoamphetamine (IMP) was estimated as an index
      of CBF in normal rats and compared with the quantitative CBF value measured using
      [15O]H2O and dynamic PET scan. A good correlation between the two values was
      obtained. The results indicate that DUR of [125I]IMP at 5 min after injection in
      rats is a useful and practical indicator of CBF since neither arterial blood
      sampling nor metabolite correction is necessary.

PMID- 15246374
TI  - New chelation strategy allows for quick and clean 99mTc-labeling of synthetic
      peptides.
AB  - Analogues of bombesin have been synthesized in which a N2S2 (bis-mercaptoacetyl
      functionalized diaminopropionic acid) or a N3S (mercaptoacetyl-Gly-Gly-Gly)
      radiometal-chelating center has been incorporated that allows radiolabeling of
      these peptides with 99mTc without the need for conjugation or harsh reaction
      conditions. A mild radiolabeling is possible by using an acetyl-moiety as sulfur
      protecting group, which can be removed by mild hydroxylamine-treatment at room
      temperature before radiolabeling. Retained receptor binding is demonstrated in
      competitive binding experiments with 99mTc-radiolabeled peptides and PC-3 cells
      with bombesin receptors.

PMID- 15246375
TI  - Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in
      [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+.
AB  - Peptide receptor-targeted radionuclide therapy is nowadays being performed with
      radiolabeled DOTA-conjugated peptides, such as [90Y-DOTA0,Tyr3]octreotide (also
      known as OctreoTher or 90Y-DOTATOC). The incorporation of 90Y3+ is typically > or
      = 99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi
      the amount of free 90Y3+ (= non-DOTA-incorporated) can be substantial. Free 90Y3+
      accumulates in bone with undesired radiation of bone marrow as a consequence. 90Y
      DTPA is excreted rapidly via the kidneys. Incorporation of free 90Y3+ into 90Y
      DTPA might prevent this fraction from being accumulated into bone, therefore we
      have investigated: the biodistribution in rats of 90YCl3, [90Y
      DOTA0,Tyr3]octreotide, and 90Y-DTPA; possibilities to complex 10% of free 90Y3+
      in a [90Y-DOTA0,Tyr3]octreotide containing solution into 90Y-DTPA prior to
      intravenous injection; and effects of 10% free 90Y3+ in [90Y
      DOTA0,Tyr3]octreotide solution, in the presence and in the absence of excess
      DTPA, on the biodistribution of in rats. The following results are presented:
      90YCl3 showed high skeletal uptake (i.e., 1% ID (injected dose) per gram femur,
      with main localization in the epiphyseal plates) and a 24 h total body retention
      of 74% ID; 90Y-DTPA had rapid renal clearance, and 24 h total body retention of <
      5% ID; added free 90Y3+ in [90Y-DOTA0,Tyr3]octreotide solution could rapidly be
      incorporated into 90Y-DTPA at room temperature; and accumulation of 90Y3+ in
      femur, blood, and liver was related to the amount of free 90Y3+, whereas these
      accumulations could be prevented by the addition of DTPA. In conclusion, the
      addition of excess DTPA to [90Y-DOTA0,Tyr3]octreotide with incomplete 90Y
      incorporation is recommended.

PMID- 15246377
TI  - Proceedings of the Fourth International Topical Meeting on Neutron Radiography
      (ITMNR-4). State College, Pennsylvania, USA, June 3-6, 2001.

PMID- 15246376
TI  - Improved yields for the in situ production of [11C]CH4 using a niobium target
      chamber.
AB  - The in situ production of [11C]CH4 using a niobium metal target chamber is
      described. Improved yields are observed in comparison to the previously reported
      aluminum conical target under similar conditions of beam energy and current. An
      empirical expression is proposed that quantifies the loss of yield as a function
      of irradiation time.

PMID- 15246380
TI  - Advances in neutron radiographic techniques and applications: a method for
      nondestructive testing.
AB  - A brief history of neutron radiography is presented to set the stage for a
      discussion of significant neutron radiographic developments and an assessment of
      future directions for neutron radiography. Specific advances are seen in the use
      of modern, high dynamic range imaging methods (image plates and flat panels) and
      for high contrast techniques such as phase contrast, and phase-sensitive imaging.
      Competition for neutron radiographic inspection may develop as these techniques
      offer application prospects for X-ray methods.

PMID- 15246381
TI  - Extended study for performances of beam quality indicator.
AB  - The performance of the beam quality indicator (BQI) was studied for confirmation
      of its reliability. An original BQI (named "BQI.org") and five newly designed
      BQIs (named "BQI.001-BQI.005") were compared with a variety of imaging systems
      with different beam spectra. With the best quality of a BQI image obtained, the
      data was carefully analyzed, and +/-1% precision was expected. However, a +/-7%
      systematic uncertainty was observed for imaging systems, including a difference
      of BQIs. Spectra of attenuation coefficients were measured using a TOF method for
      Pb and Ti, which was used to define a calibration curve for the BQIs. The curve
      will be compared with the previously defined calibration curve for the BQI.org.

PMID- 15246382
TI  - A new fast and large area neutron detector using a novel image plate readout
      technique.
AB  - At Agfa Medical Imaging Systems, a new type of image plate scanner is being
      developed. Instead of scanning the irradiated image plate with a single laser and
      reading the luminescence information with a single light collector and
      photomultiplier, the new system employs a whole line of laser diodes and a set of
      CCD line sensors. This technique allows for virtually unlimited detection areas
      and a very fast readout.

PMID- 15246383
TI  - Energy-selective neutron radiography and tomography at FRM.
AB  - At the reactor FRM at Technical University of Munich energy-selective neutron
      radiography and tomography experiments were performed. For an energy separation
      of the neutrons from the primary beam a mechanical velocity selector was used.
      The radiography images show a different contrast of the investigated elements for
      neutron energies below and above their Bragg-cutoff energy. A comparison between
      the standard and energy-selective neutron tomography is presented. In spite of a
      reduction of the neutron intensity due to the velocity selector technique a
      realistic experimental time in order of some hours for the tomography experiment
      was achieved.

PMID- 15246384
TI  - Recognition of internal structure of unknown objects with simultaneous neutron
      and gamma radiography.
AB  - Generally speaking in customary industrial and medical radiography, there is no
      tendency to reveal the nature of the samples. Ordinarily, the main objective of
      taking a radiograph is to show the position and dimension of unknown parts,
      inside the test object and to determine cracks, defects, etc. Whereas in
      radiography many important factors such as material cross-sections and build-up
      factors are also involved. In this paper, by using both neutron and gamma
      radiography techniques, some mathematical relations were successfully generated,
      in order to calculate the neutron and gamma total macroscopic cross-sections of
      some unknown elements in the presence of the other elements. For this work, some
      test pieces were defined and made of lead, silver, copper, Nickel, tin, graphite
      and polyethylene. The neutron radiography facility at Tehran Research Reactor
      (TRR) was used as mixed neutron and gamma radiography source (Proceedings of the
      Second World Conference on Neutron Radiography, Paris, France, pp. 25-32). On
      testing of a correction of the above-mentioned generated relations, a new
      technique of simultaneous neutron and gamma radiography was also investigated.

PMID- 15246385
TI  - Statistical image analysis of high-sensitivity neutron images obtained by cooled
      CCD systems.
AB  - Neutron sensitivity and noise characteristics of cooled CCD NR systems were
      investigated. Eighteen species of neutron sensitive scintillators were tested by
      the use of two types of cooled CCD devices. The statistical analysis of the S/N
      ratio of the neutron images showed that the ZnS+LiF type was the highest
      sensitivity scintillator. The generation rate of the CCD noises increased with
      increasing exposure time, temperature of the device and dose rate of the
      environmental radiation. The generation rate and the pulse height distribution of
      the noise were quite different between the two CCD devices. Thus, the origin of
      the noise is considered to be strongly related to the internal structure of the
      CCD devices.

PMID- 15246386
TI  - Neutron imaging of Zr-1%Nb fuel cladding material containing hydrogen.
AB  - Hydrogen distribution and hydride phases were analyzed in reactor fuel cladding
      pressure tube Zr-1%Nb material up to 13,300 ppm. From neutron diffraction
      measurements, formation of cubic delta-ZrH2 and a small amount of tetragonal
      gamma-ZrH was established. Texture effects were analyzed by imaging plate
      technique. From neutron radiography images a linear model was set up that
      adequately described the relationship between gray levels and nominal H
      concentrations. The H-distribution was unveiled by 3D intensity histograms and
      fractal analysis of multilevel-segmented neutron radiography images.

PMID- 15246387
TI  - Optimization of the beam geometry for the cold neutron tomography facility at the
      new neutron source in Munich.
AB  - One of the very interesting applications at Munich's New Neutron Source will be
      neutron tomography. It will be used both for research and industry. The D2O
      moderated high flux reactor will provide thermal neutrons for the structural
      analysis of specimen up to the size of 1 m. A central problem is the design of
      the beam geometry, especially the layout of the collimator and the aperture.
      Calculations were carried out in order to get an optimal beam geometry, taking
      into consideration an extended source, low beam divergency and high flux in the
      detector plane.

PMID- 15246388
TI  - Neutron radiography of porous rocks and iron ore.
AB  - Neutron radiography can provide images of the internal structure of rocks,
      through virtue of the differing neutron attenuation characteristics of hydrogen
      versus other elements commonly found in nature. Thus, pores filled with water, or
      oil, will attenuate neutrons to a greater extent than the surrounding rock
      matrix. Similarly, the internal structure of iron ore, which contains mixtures of
      limonite and goethite, which contain hydrogen in their crystalline lattice, and
      magnetite (no hydrogen), can also be imaged using neutrons. The ability of the
      technique to distinguish "effective porosity" versus "total porosity" is derived
      from the neutron radiographs. Images of two iron ore samples have also been
      analyzed to demonstrate how both different mineral assemblages and porosity can
      be determined.

PMID- 15246389
TI  - Neutron gamma ray radiography using a two-color luminescent scintillator.
AB  - Neutron and gamma ray radiographs has been obtained using red and green images on
      a two-color luminescent scintillator using a cooled color CCD camera at the
      thermal neutron radiography field of JRR-3m.

PMID- 15246390
TI  - Hydrogen distribution measurements by neutrons.
AB  - The paper describes how hydrogenous materials can be investigated with state-of
      the-art neutron radiography detection methods. The methodical problems for a
      precise quantification and steps towards their solution are demonstrated. Based
      on several practical examples, the diversity of problems to be solved by neutron
      imaging is illustrated.

PMID- 15246391
TI  - Semi-simultaneous application of neutron and X-ray radiography in revealing the
      defects in an Al casting.
AB  - A semi-simultaneous application of neutron and X-ray radiography (NR, XR)
      respectively, was applied to an Al casting. The experiments were performed at the
      10MW VVR-SM research reactor in Budapest (Hungary). The aim was to reveal,
      identify and parameterize the hidden defects in the Al casting. The joint
      application of NR and XR revealed hidden defects located in the Al casting. Image
      analysis of the NR and XR images unveiled a cone-like dimensionality of the
      defects. The spectral density analysis of the images showed a distinctly
      different character for the hidden defect region of Al casting in comparison with
      that of the defect-free one.

PMID- 15246392
TI  - Non-destructive 10B analysis in neutron transmission experiments.
AB  - Boron alloyed stainless-steel sheets are predominantly used in nuclear
      engineering as neutron shielding for radioactive waste disposal equipment. The
      neutron absorption depends strongly on the amount and the distribution of the 10B
      isotope. A systematic transmission study of 10B enriched steel plates by means of
      neutron time-of-flight and neutron radiography experiments was performed. The 10B
      content was analyzed with accuracy up to 5 x 10(-3) wt% using monochromatic beams
      and a linear increase of the macroscopic cross section with the 10B content was
      found even for strong absorbers. Then we extended the transmission analysis to
      "white" thermal neutron beams where large deviations from the exponential
      transmission law are observed. The influence of the spectral width is discussed
      in more detail because beam hardening causes an elevation of the effective
      transmission through strong absorbing materials, an effect which is crucial for
      the design of neutron shielding.

PMID- 15246393
TI  - Recent developments and applications for the University of Texas Thermal Neutron
      Imaging Facility.
AB  - The Thermal Neutron Imaging Facility (UT-TNIF) at the University of Texas at
      Austin is being modified to begin work with the non-destructive evaluation of
      carbon fiber composite materials intended for use in space. The use of high
      resolution borated micro channel plate (MCP) detectors has been investigated.
      MCNP calculations to redesign the external radiation shielding to allow UT-TNIF
      operation at higher reactor powers and to minimize internal neutron scattering
      have been performed.

PMID- 15246394
TI  - Prospects for efficient detectors for fast neutron imaging.
AB  - A physical model describing in detail the process of fast neutron imaging in
      luminescent screens is presented. The detection quantum efficiency, luminosity
      and inherent spatial resolution of the screen were calculated using this model.
      Properties of transparent and disperse screens were compared. Two imaging systems
      were suggested to improve the detection efficiency and spatial resolution. A
      stack consisting of alternating neutron converters and image plates can help in
      obtaining both high spatial resolution and efficiency. A system containing a
      screen of special form and a diaphragm can be of use especially in the case of
      the fan beam.

PMID- 15246395
TI  - Radiography and tomography with fast neutrons at the FRM-II--a status report.
AB  - For the basic instrumentation of the new research reactor FRM-II, Munich, a
      radiography/tomography facility using fast neutrons is under construction. The
      main features of the facility and results of simulation studies on characteristic
      parameters are presented.

PMID- 15246396
TI  - Trial of very cold neutron radiography in Kyoto University reactor.
AB  - A practical very cold neutron (VCN) radiography using a neutron imaging plate was
      carried out in VCN facility, Kyoto University Reactor (KUR: 5MW). The neutron
      flux from the VCN bender with the characteristic wavelength of 4.8 nm gives a
      good image with 5 min irradiation time when CNS was operated. The macroscopic
      total cross sections of water were measured by imaging plates. It is
      Sigma(th)=0.87 cm(-1) measured in KUR E2 thermal neutron radiography facility and
      that of VCN is Sigma(VCN)=9.4 cm(-1). The resolution of water thickness is less
      than 0.1 mm for VCN radiography and close to the positional resolution of an
      imaging plate. VCN radiography can show the change of water quantity in
      gypsophila during a drying procedure.

PMID- 15246397
TI  - Thermal and cold neutron phase-contrast radiography.
AB  - In this paper, we will discuss a phase-contrast imaging method that avoids the
      complications of interferometry to provide phase contrast in weakly absorbing
      samples. A transversely coherent neutron beam is used with the traditional
      radiography scheme. Images taken with this scheme show dramatic intensity
      variations due to sharp changes in the neutron wave refractive index. With some
      numerical processing these images may be used to reconstruct a quantitative phase
      radiograph of specimens imaged with this technique.

PMID- 15246398
TI  - Neutron tomography developments and applications.
AB  - Neutron radiography has been in use as a nondestructive testing technique for the
      past 50 years. The neutrons' unique ability to image certain elements and
      isotopes that are either completely undetectable or poorly detected by other NDI
      methods makes neutron radiography an important tool for the NDI community.
      Neutron radiography like other imaging techniques takes a number of different
      forms (i.e., film, radioscopic, transfer methods, tomography, etc.) This paper
      will describe the neutron tomography system developed at the University of
      California, Davis McClellan Nuclear Radiation Center (UC Davis/MNRC), and the
      applications for both research and commercial uses. The neutron radiography
      system at the UC Davis/MNRC has been under development for 4 years. The initial
      system was developed to find very low concentrations of hydrogen (i.e., <200
      ppm). In order to achieve these low detection levels, it was necessary to perform
      both pre- and post-processing of the tomographs. The pre-processing steps include
      corrections for spatial resolution and random noise effects. Images are corrected
      for systematic noise errors and beam hardening. From these data the attenuation
      coefficient is calculated. The post-processing steps include alignment of the
      collected images, determining the center of mass, and, finally, using the
      filtered back-projection routine from the Donner Algorithms Library to obtain the
      final images. Since its initial development, the tomography system has been used
      very successfully to find low levels of hydrogen in a metal matrix. Further uses
      of the system have been to verify the exact placement, in three dimensions, of "O
      rings" in large metal valve bodies, and to map the location and extent of veins
      in porous and high-density rocks of various different kinds. These examples show
      that neutron tomography is becoming a needed inspection technique for the 21st
      century.

PMID- 15246399
TI  - Region of interest tomography of bigger than detector samples.
AB  - For many neutron tomography setups, the maximum sample size for tomography is
      limited by a comparatively small beam cross section. However, it is not well
      known outside the medical field that it is possible to perform region-of-interest
      tomography of sections inside the object that fit into the beam and detector
      area. Approximately valid reconstruction data appear in a circle with a diameter
      of approximately the detector width, but with incomplete data and strong
      artifacts outside that circle. These artifacts can be removed either by
      mathematical means or by simple geometrical cutting of the reconstructed data,
      enabling the examination of samples bigger than the detector or beam area.

PMID- 15246400
TI  - The use of amorphous silicon flat panels as detector in neutron imaging.
AB  - A first test for neutron detection with a flat panel device based on the
      amorphous silicon technology is described in this report. The most important
      parameters defining the performance for neutron imaging are described. The first
      findings are encouraging for further improvements.

PMID- 15246401
TI  - Performance comparison of neutron and X-ray sensitive photo-stimulated imaging
      plates.
AB  - Statistical characteristics of photo-stimulated luminescent (PSL) signals are
      studied using thermal neutrons, X- and gamma-rays. It is shown that the
      statistical fluctuation of PSL is described simply by the PSL value itself and is
      independent of radiation type, except for short-range high-LET particles.
      However, it is expected that the spatial resolution should be affected if the
      range of electrons or secondaries were much longer than the instrumental
      resolution (pixel size). When output PSL signals are compared between X- and
      gamma-rays, the PSL values were proportional to the exposed air dose, independent
      of X-ray energy. However, signals from 60Co gamma-rays were approximately 1% of
      22-40 kV X-ray output at the same dose.

PMID- 15246402
TI  - High-energy and thermal-neutron imaging and modeling with an amorphous silicon
      flat-panel detector.
AB  - The Los Alamos Neutron Science Center (LANSCE) operates two spallation neutron
      sources dedicated to research in materials science, condensed-matter physics, and
      fundamental and applied nuclear physics. Prior to 1995, all thermal neutron
      radiography at Los Alamos was done on a beam port attached to the Omega West
      reactor, a small 8MW research reactor used primarily for radioisotope production
      and prompt and delayed neutron activation analysis. After the closure of this
      facility, two largely independent radiography development efforts were begun at
      LANSCE using moderated cold and thermal neutrons from the Target-1 source and
      high-energy neutrons from the Target-4 source. Investigations with cold and
      thermal neutrons employed a neutron converter and film, a scintillation screen
      and CCD camera system, and a new high-resolution amorphous silicon (a-Si) flat
      panel detector system. Recent work with high-energy neutrons (En > 1 MeV) has
      involved storage-phosphor image plates. Some comparison high-energy images were
      obtained with both image plates and the a-Si panel and showed equivalent image
      quality for approximately equal exposure times.

PMID- 15246403
TI  - Neutron capture autoradiographic study of the biodistribution of 10B in tumor
      bearing mice.
AB  - For the study on boron neutron capture therapy, the whole-body sections of tumor
      bearing mice infused with 10B attached to CR-39 plastic track detectors were
      exposed to thermal and cold neutron beams. Neutron capture autoradiographic
      images obtained by the cold neutron irradiation were extremely superior in
      quality to those of the thermal neutron beams. From the autoradiographic images,
      the 10B reaction dose of the neutron-induced particles was estimated using the
      differential LET distribution.

PMID- 15246404
TI  - Analysis and testing of the divergence and alignment indicator using the Penn
      State neutron radiography beam.
AB  - The divergence and alignment indicator (DAI) was developed to test the alignment
      of the imaging plane in a neutron beam and to determine the divergence angle of
      the beam. The construction of the device was intentionally kept simple to allow
      ease of implementation. The DAI consists of an aluminum plate and rods, and
      cadmium wire for contrast. The device was tested in the Pennsylvania State
      University Breazeale Nuclear Reactor neutron radiography beam. Three basic cases
      (aligned, aligned in only one direction, and completely misaligned), were used to
      determine that the derived equations for calculating the beam divergence were
      correct for each case. During the use of a newly fabricated DAI device, it was
      discovered that the most prominent weakness of the DAI is the precision necessary
      in the construction. For example, the top of the plate must be precisely flat.
      Otherwise, the minor differences in height will lead to large discrepancies in
      the data.

PMID- 15246405
TI  - Analyzing of segregation in mixtures of 3-methylpyridine and heavy water by
      dynamic neutron radiography.
AB  - The closed-loop phase diagram of 3-methylpyridine-heavy water mixture was
      studied, to our best knowledge, for the first time with dynamic neutron
      radiography (DNR) at the 10MW VVR-SM Research Reactor in Budapest (Hungary).
      Visualized were the (i) lower temperature non-segregated states (below 38 degrees
      C), (ii) transition (40-43 degrees C), (iii) segregated states (46-128 degrees
      C), (iv) higher temperature transition (110-128 degrees C) and (v) higher
      temperature non-segregated states. The non-segregated state belonging to 141
      degrees C, was found to be definitely dissimilar from the lower temperature
      state. Existence of a solid-like structure at the liquid-liquid interface was
      indicated.

PMID- 15246406
TI  - Study of material changes of SINQ target rods after long-term exposure by neutron
      radiography methods.
AB  - This paper describes the results of non-destructive investigations by indirect
      neutron radiography methods obtained at the facility NEUTRA [Nondestruct. Testing
      Eval. 16 (2000b) 203], spallation neutron source SINQ [Operating experience and
      development projects at SINQ, PSI Report 98-04, ISSN 1019-0643]. Target rods from
      the second SINQ metal target were removed after 6 Ah of proton beam exposure and
      studied under well-shielded conditions. No real damage was found at one of the 11
      observed rods and one tube. However, hydrogen accumulation could be identified
      inside the zircaloy rods and the steel rods as well. Whereas the hydrogen has a
      homogenous distribution in Zr (with the peak value near the centre of the applied
      beam), the steel samples show clusters of hydrogen near the edge of the Zr
      cladding. Lead (in steel cladding) was found modified by accumulations of
      spallation products, mainly mercury. In the radiography images, a depression of
      the neutron field was observed due to the absorption by mercury. The applied
      method with Dy and In as neutron converters and imaging plates [Nucl. Instrum.
      Methods 377 (1996) 119] as secondary detectors seems to be optimal for such kind
      of investigations, especially when quantitative considerations have to be made.

PMID- 15246407
TI  - Neutron radiography and other NDE tests of main rotor helicopter blades.
AB  - A few nondestructive examination (NDE) techniques are extensively being used
      worldwide to investigate aircraft structures for all types of defects. The
      detection of corrosion and delaminations, which are believed to be the major
      initiators of defects leading to aircraft structural failures, are addressed by
      various NDE techniques. In a combined investigation by means of visual
      inspection, X-ray radiography and shearography on helicopter main rotor blades,
      neutron radiography (NRad) at SAFARI-1 research reactor operated by Necsa, was
      performed to introduce this form of NDE testing to the South African aviation
      industry to be evaluated for applicability. The results of the shearography,
      visual inspection and NRad techniques are compared in this paper. The main
      features and advantages of neutron radiography, within the framework of these
      investigations, will be highlighted.

PMID- 15246408
TI  - The drying process of concrete: a neutron radiography study.
AB  - The natural drying process of concrete, which has a significant effect on its
      characteristics, for example durability, was studied at the neutron radiography
      facility at SAFARI-1 nuclear research reactor, operated by Necsa. Monitoring of
      the movement of the water in concrete samples, which were wet cured for one day
      and covered on all the sides but one, was done by means of a CCD camera system.
      In this paper the methodology in observing the drying process will be described
      together with results obtained from this investigation. The measured water
      content and porosity results were quantified and compared reasonably well with
      conventional gravimetrical measurements.

PMID- 15246409
TI  - Image processing methods to obtain symmetrical distribution from projection
      image.
AB  - Flow visualization and measurement of cross-sectional liquid distribution is very
      effective to clarify the effects of obstacles in a conduit on heat transfer and
      flow characteristics of gas-liquid two-phase flow. In this study, two methods to
      obtain cross-sectional distribution of void fraction are applied to vertical
      upward air-water two-phase flow. These methods need projection image only from
      one direction. Radial distributions of void fraction in a circular tube and a
      circular-tube annuli with a spacer were calculated by Abel transform based on the
      assumption of axial symmetry. On the other hand, cross-sectional distributions of
      void fraction in a circular tube with a wire coil whose conduit configuration
      rotates about the tube central axis periodically were measured by CT method based
      on the assumption that the relative distributions of liquid phase against the
      wire were kept along the flow direction.

PMID- 15246410
TI  - Characterization of HANARO neutron radiography facility in accordance with ASTM
      standard E545-91/E803-91 for KOLAS/ISO17025.
AB  - As neutron radiography is even more in demand for industrial applications of
      aircraft, turbine blade, automobile, explosive igniters, etc, it is necessary to
      review the standards which are the most appropriate for preparing the procedures
      for setting up the QA system. Recently, Korea Of Lab Accreditation Scheme (KOLAS)
      was originated from ISO 17025. It is widely recognized by research peer groups
      for conducting valid tests. The neutron radiography facility (NRF) of High Flux
      Advanced Neutron Application Reactor (HANARO), which started ion 1996, is the
      preliminary stages of KOLAS. The HANARO NRF is not only characterized using ASTM
      standards E545-91/E803-91 to satisfy the requirements of KOLAS, but in the design
      phase of the tomography system.

PMID- 15246411
TI  - Accumulation of boron compounds to tumor with polyethylene-glycol binding
      liposome by using neutron capture autoradiography.
AB  - The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear
      reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B
      atoms to the tumor cells selectively for effective BNCT. In order to achieve an
      accurate measurement of 10B concentrations in the biological samples, we employed
      a technique of neutron capture autoradiography (NCAR) of the sliced whole-body
      samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39
      detectors attached with samples were exposed to thermal neutrons in the thermal
      column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo
      University and thermal neutron facility of Paul Scherer Institute(PSI). We
      obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B
      transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the
      tumor tissue of mice were estimated by means of alpha-track density measurements.
      In this study, we can increase the accumulation of 10B atoms in the tumor tissues
      by binding polyethylene-glycol chains to the surface of liposome, which increase
      the retention in the blood flow and escape the phagocytosis by reticulo
      endothelial systems. Therefore, we will be able to apply NCAR technique for
      selection of effective 10B carrier in BNCT for cancer.

PMID- 15246413
TI  - The design of the neutron radiography and tomography facility at the new research
      reactor FRM-II at Technical University Munich.
AB  - The new reactor FRM-II of Technical University Munich will offer a professional
      radiography and tomography facility for industrial use. The concept of the
      instrument and the optimization under the conditions imposed by the surrounding
      instruments are described for the first installment and for a second stage in an
      external experimental hall in about 5 years. Several detector systems for
      different applications will be employed and a short description of their
      possibilities is given.

PMID- 15246412
TI  - Assessing cadmium distribution applying neutron radiography in moss trophical
      levels, located in Szarvasko, Hungary.
AB  - The measuring station of the 10 MW VVR-SM research reactor at the Budapest
      Neutron Centre (Hungary) was used to perform dynamic neutron radiography (DNR),
      which was, to our best knowledge, the first time, in a Tortella tortuosa biotope.
      In the conducted study, two trophical levels, moss and spider Thomisidae sp.
      juv., were examined. Cadmium penetration routes, distribution and accumulation
      zones were visualized in the leafy gametophyte life cycle of Tortella tortuosa
      and in the organs of the spider.

PMID- 15246414
TI  - A mobile neutron source based on the SbBe reaction.
AB  - Optimisation studies on the layout of a SbBe neutron source for application in
      mobile thermal neutron radiography or tomography measurements have been performed
      using MCNP and shielding calculations. Results and the actual status in the set
      up of the source are presented.

PMID- 15246415
TI  - Monte Carlo design for a new neutron collimator at the ENEA Casaccia TRIGA
      reactor.
AB  - The TRIGA RC-1 1MW reactor operating at ENEA Casaccia Center is currently being
      developed as a second neutron imaging facility that shall be devoted to computed
      tomography as well as neutron tomography. In order to reduce the gamma-ray
      content in the neutron beam, the reactor tangential piercing channel was
      selected. A set of Monte Carlo simulation was used to design the neutron
      collimator, to determine the preliminary choice of the materials to be employed
      in the collimator design.

PMID- 15246416
TI  - Void fraction and velocity measurement of simulated bubble in a rotating disc
      using high frame rate neutron radiography.
AB  - To evaluate measurement error of local void fraction and velocity field in a gas
      molten metal two-phase flow by high-frame-rate neutron radiography, experiments
      using a rotating stainless-steel disc, which has several holes of various
      diameters and depths simulating gas bubbles, were performed. Measured
      instantaneous void fraction and velocity field of the simulated bubbles were
      compared with the calculated values based on the rotating speed, the diameter and
      the depth of the holes as parameters and the measurement error was evaluated. The
      rotating speed was varied from 0 to 350 rpm (tangential velocity of the simulated
      bubbles from 0 to 1.5 m/s). The effect of shutter speed of the imaging system on
      the measurement error was also investigated. It was revealed from the Lagrangian
      time-averaged void fraction profile that the measurement error of the
      instantaneous void fraction depends mainly on the light-decay characteristics of
      the fluorescent converter. The measurement error of the instantaneous local void
      fraction of simulated bubbles is estimated to be 20%. In the present imaging
      system, the light-decay characteristics of the fluorescent converter affect the
      measurement remarkably, and so should be taken into account in estimating the
      measurement error of the local void fraction profile.

PMID- 15246417
TI  - Neutron radiography inspection of investment castings.
AB  - Investment casting, also known as the lost wax process, is a manufacturing method
      employed to produce near net shape metal articles. Traditionally, investment
      casting has been used to produce structural titanium castings for aero-engine
      applications with wall thickness less than 1 in (2.54 cm). Recently, airframe
      manufacturers have been exploring the use of titanium investment casting to
      replace components traditionally produced from forgings. Use of titanium
      investment castings for these applications reduces weight, cost, lead time, and
      part count. Recently, the investment casting process has been selected to produce
      fracture critical structural titanium airframe components. These airframe
      components have pushed the traditional inspection techniques to their physical
      limits due to cross sections on the order of 3 in (7.6 cm). To overcome these
      inspection limitations, a process incorporating neutron radiography (n-ray) has
      been developed. In this process, the facecoat of the investment casting mold
      material contains a cocalcined mixture of yttrium oxide and gadolinium oxide. The
      presence of the gadolinium oxide, allows for neutron radiographic imaging (and
      eventual removal and repair) of mold facecoat inclusions that remain within these
      thick cross sectional castings. Probability of detection (POD) studies have shown
      a 3 x improvement of detecting a 0.050 x 0.007 in2 (1.270 x 0.178 mm2) inclusion
      of this cocalcined material using n-ray techniques when compared to the POD using
      traditional X-ray techniques. Further, it has been shown that this n-ray
      compatible mold facecoat material produces titanium castings of equal
      metallurgical quality when compared to the traditional materials. Since
      investment castings can be very large and heavy, the neutron radiography
      facilities at the University of California, Davis McClellan Nuclear Radiation
      Center (UCD/MNRC) were used to develop the inspection techniques. The UCD/MNRC
      has very unique facilities that can handle large parts up to 39 ft (12 m) in
      length and 13 ft (4 m) high weighing up to 5000 lbs (2300 kg). These handling
      systems are robotically driven. The neutron radiographic system consists of a
      highly thermalized neutron beam. The neutron beam has an intensity of 5.6 x 10(6)
      n/cm2 s, with a L/D = 200 at a power of 2 MW. A divergent beam collimator is used
      which provides a beam of approximately 22 in (56 cm) in diameter at the film
      plane. A vacuum cassette with a gadolinium vapor deposited screen is used to
      collect the image. Exposure times can be as short as 3 min, or up to 30 min.

PMID- 15246418
TI  - Velocity field measurement in gas-liquid metal two-phase flow with use of PIV and
      neutron radiography techniques.
AB  - To establish reasonable safety concepts for the realization of commercial liquid
      metal fast breeder reactors, it is indispensable to demonstrate that the release
      of excessive energy due to re-criticality of molten core could be prevented even
      if a severe core damage accident took place. Two-phase flow due to the boiling of
      fuel-steel mixture in the molten core pool has a larger liquid-to-gas density
      ratio and higher surface tension in comparison with those of ordinary two-phase
      flows such as air-water flow. In this study, to investigate the effect of the
      recirculation flow on the bubble behavior, visualization and measurement of
      nitrogen gas-molten lead bismuth in a rectangular tank was performed by using
      neutron radiography and particle image velocimetry techniques. Measured flow
      parameters include flow regime, two-dimensional void distribution, and liquid
      velocity field in the tank. The present technique is applicable to the
      measurement of velocity fields and void fraction, and the basic characteristics
      of gas-liquid metal two-phase mixture were clarified.

PMID- 15246419
TI  - Development of neutron radioscopy for the inspection of CF188 flight control
      surfaces.
AB  - Neutron radioscopy, using a cooled charged coupled device (CCD) camera and a
      neutron-sensitive scintillation screen, was developed at the SLOWPOKE-2 Facility
      at the Royal Military College (RMC) to detect water ingress into the composite
      layers and the aluminium honeycomb core in flight control surfaces on the CF188
      Hornet aircraft. The response of the CCD camera system was tested at different
      neutron fluxes utilising the SLOWPOKE-2 at RMC and the Breazeale Nuclear Reactor
      at Pennsylvania State University.

PMID- 15246420
TI  - Study of a loop heat pipe using neutron radiography.
AB  - An explanation is given of what a loop heat pipe (LHP) is, and how it works. It
      is then shown that neutron imaging (both real time neutron radioscopy and single
      exposure neutron radiography) is an effective experimental tool for the study of
      LHPs. Specifically, neutron imaging has helped to identify and correct a cooling
      water distribution problem in the condenser, and has enabled visualization of two
      phase flow (liquid and vapor) in various components of the LHP. In addition,
      partial wick dry-out, a phenomenon of great importance in the effective operation
      of LHPs, is potentially identifiable with neutron imaging. It is anticipated that
      neutron radioscopy and radiography will greatly contribute to our understanding
      of LHP operation, and will lead to improvement of LHP modeling and design.

PMID- 15246421
TI  - Visualization and void fraction measurement of gas-liquid two-phase flow in plate
      heat exchanger.
AB  - Adiabatic and boiling gas-liquid two-phase flows in a simulated plate heat
      exchanger with a single-ribbed channel were visualized by a thermal neutron
      radiography method. In the experiments under adiabatic condition, the air-water
      two-phase flows in an aluminum test section were visualized. In the boiling two
      phase flow experiments, chlorofluorocarbon R141b was used as the working fluid.
      Two-dimensional distributions of void fraction were measured from visualized
      images via some image processing techniques. As a result, it was shown that both
      the phases tended to flow straight in the ribbed channel, and mixing of gas and
      liquid phases was weak. Moreover, when working fluids flew into the test section
      as a gas-liquid mixture, the phase distributions were strongly affected by a
      liquid pool at the test section inlet.

PMID- 15246422
TI  - Quantitative flow visualization of fluidized-bed heat exchanger by neutron
      radiography.
AB  - Quantitative flow visualization of a gas-solid fluidized-bed installed vertical
      tube-bank has been successfully conducted using neutron radiography and image
      processing technique. The quantitative data of void fraction distribution as well
      as the fluctuation data are presented. The time-averaged void fraction is well
      correlated by the drift-flux model. The bubbles formed in the bed, rise along the
      vertical tubes and the observed bubble size is smaller than that in a free
      bubbling bed without tube-banks. The bubble diameter is well correlated by the
      modified Mori and Wen's correlation taking into account the pitch of tube
      arrangement. The bubble rise velocity is also well correlated by applying the
      drift-flux model. These results are consistent for both bed materials of
      Geldart's B- and A-particles, while the bubble size is significantly different
      between two kinds of particles.

PMID- 15246423
TI  - A trial of quantitative estimation of Al-corrosion detected by neutron
      radiography.
AB  - Comparing the hydrogen content in aluminum hydroxides, one of the main components
      of Al-corrosion, with that in polyethylene sheets, corroded degree of practical
      Al-corrosions were estimated quantitatively by neutron radiography.

PMID- 15246424
TI  - Linking tumor suppression, DNA damage and the anaphase-promoting complex.
AB  - A recent study shows that the RASSF1A tumor suppressor functions as a regulator
      of the ordered proteolytic steps that organize mitosis. By controlling the
      stability of microtubules and the activity of the anaphase-promoting complex
      (APC), RASSF1A might provide a crucial link between mechanisms of tumor
      suppression and mitotic cell division. Furthermore, another recent study shows
      that protein kinase A, which is a key growth regulator, inhibits the APC during
      mitosis in yeast.

PMID- 15246425
TI  - Chloroplast protein import: solve the GTPase riddle for entry.
AB  - The fidelity of the numerous intracellular protein-trafficking pathways to
      different organelles is dictated by the interactions between the intrinsic
      targeting signals of substrate proteins and specific receptors that deliver the
      substrate to the proper organelle. Recent studies of protein targeting to
      chloroplasts suggest a novel mechanism in which GTP-dependent substrate
      recognition is coupled to a GTP-driven motor that initiates the translocation of
      proteins into the organelle.

PMID- 15246426
TI  - Phosphatases join kinases in DNA-damage response pathways.
AB  - An inappropriate imbalance of kinase and phosphatase activities could be
      deleterious to cellular processes such as proliferation. Cellular responses to
      DNA damage use signal-transduction pathways involving phosphorylation events, and
      such modifications must be reversible to make these responses transient, rather
      than permanent, events. Three recent articles describe roles for two phosphatases
      in signaling pathways that are activated after DNA damage.

PMID- 15246427
TI  - On phagosome individuality and membrane signalling networks.
AB  - Cells such as macrophages take up pathogens into specialized membrane organelles
      (phagosomes) that fuse with other organelles, including lysosomes, in a process
      termed maturation. The fully matured phagolysosome is a low-pH, hydrolase-rich
      killing device that some pathogens can bypass. One might expect that phagosomes
      containing a given type of particle that entered cells simultaneously via the
      same receptor would behave the same, at least in a single cell. Surprisingly,
      however, recent data show that phagosomes formed via the same receptors can find
      themselves in different chemical states even within the same macrophage. Here, I
      argue that each phagosome is an individual entity whose behaviour depends on a
      finite number of stable equilibrium states in its membrane signalling networks.

PMID- 15246428
TI  - Seeing is believing: imaging actin dynamics at single sites of endocytosis.
AB  - Endocytosis is characterized by movement and precisely controlled changes in
      membrane geometry during vesicle formation. Recent developments in live-cell
      imaging have enabled such movements to be monitored in vivo and correlated with
      the recruitment and dismissal of fluorescently labeled proteins. This
      experimental strategy has revealed the sequential recruitment of proteins that
      are involved in actin polymerization, and actin to single sites of endocytosis in
      both yeast and mammalian cells. Actin polymerization is correlated with the
      inward movements of endocytic organelles, which suggests that actin
      polymerization has a conserved role in this process. In this article, I will
      discuss three models for the role of actin polymerization in endocytosis.

PMID- 15246429
TI  - Building the centromere: from foundation proteins to 3D organization.
AB  - At each mitosis, accurate segregation of every chromosome is ensured by the
      assembly of a kinetochore at each centromeric locus. Six foundation kinetochore
      proteins that assemble hierarchically and co-dependently have been identified in
      vertebrates. CENP-A, Mis12, CENP-C, CENP-H and CENP-I localize to a core domain
      of centromeric chromatin. The sixth protein, CENP-B, although not essential in
      higher eukaryotes, has homologues in fission yeast that bind pericentric DNA and
      are essential for heterochromatin formation. Foundation kinetochore proteins have
      various roles and mutual interactions, and their associations with centromeric
      DNA and heterochromatin create structural domains that support the different
      functions of the centromere. Advances in molecular and microscopic techniques,
      coupled with rare centromere variants, have enabled us to gain fresh insights
      into the linear and 3D organization of centromeric chromatin.

PMID- 15246430
TI  - Digging deep into the pockets of orphan nuclear receptors: insights from
      structural studies.
AB  - Nuclear receptors comprise a large family of proteins that shares a common
      structure and mechanism of action. Members of this family, first cloned 20 years
      ago, are regulated by small lipophilic signaling molecules such as steroid
      hormones, retinoids and thyroid hormone. More recently, the characterization of
      proteins that resemble nuclear receptors (referred to as orphan receptors) has
      resulted in the determination of novel signaling pathways. However, many orphan
      receptor ligands remain unidentified, and recent structural studies of the
      binding domains for orphan-receptor ligands suggest that not all of these
      receptors use ligand binding in a classical way. Notably, it is now evident that
      some orphan receptors lack the capacity for ligand binding, which suggests that
      they are regulated by alternative, ligand-independent mechanisms.

PMID- 15246431
TI  - GAP control: regulating the regulators of small GTPases.
AB  - The small GTPases of the Ras superfamily mediate numerous biological processes
      through their ability to cycle between an inactive GDP-bound and an active GTP
      bound form. Among the key regulators of GTPase cycling are the GTPase-activating
      proteins (GAPs), which stimulate the weak intrinsic GTP-hydrolysis activity of
      the GTPases, thereby inactivating them. Despite the abundance of GAPs and the
      fact that mutations in GAP-encoding genes underlie several human diseases, these
      proteins have received relatively little attention. Recent studies have addressed
      the regulatory mechanisms that influence GAP activity. So far, findings suggest
      that GAP activity is regulated by several mechanisms, including protein-protein
      interactions, phospholipid interactions, phosphorylation, subcellular
      translocation and proteolytic degradation.

PMID- 15246432
TI  - Regulation of cytoskeletal dynamics by actin-monomer-binding proteins.
AB  - The actin cytoskeleton is a vital component of several key cellular and
      developmental processes in eukaryotes. Many proteins that interact with
      filamentous and/or monomeric actin regulate the structure and dynamics of the
      actin cytoskeleton. Actin-filament-binding proteins control the nucleation,
      assembly, disassembly and crosslinking of actin filaments, whereas actin-monomer
      binding proteins regulate the size, localization and dynamics of the large pool
      of unpolymerized actin in cells. In this article, we focus on recent advances in
      understanding how the six evolutionarily conserved actin-monomer-binding proteins
      - profilin, ADF/cofilin, twinfilin, Srv2/CAP, WASP/WAVE and verprolin/WIP -
      interact with actin monomers and regulate their incorporation into filament ends.
      We also present a model of how, together, these ubiquitous actin-monomer-binding
      proteins contribute to cytoskeletal dynamics and actin-dependent cellular
      processes.

PMID- 15246433
TI  - Rita Levi-Montalcini: the discovery of nerve growth factor and modern
      neurobiology.
AB  - The remarkable accomplishments in developmental neurobiology within the past 60
      years have depended on two things: (i) a succession of original histochemical and
      immunohistochemical methodologies for identifying pathways in the nervous system
      with increasing precision and sensitivity, and (ii) the discovery of growth
      factors for neurons. Growth factors are naturally occurring, essential biological
      mediators that promote cell growth, differentiation, survival and function in
      specific nerve cell populations. The discovery of nerve growth factor (NGF) by
      Rita Levi-Montalcini in the 1950s represents an important milestone in the
      processes that led to modern cell biology. NGF was the first growth factor
      identified, for its action on the morphological differentiation of neural-crest
      derived nerve cells. Later, its effect on neuronal cells of the peripheral and
      central nervous systems, and on several non-neuronal cells was also determined.
      Thus, Levi-Montalcini's work on NGF represents, as acknowledged by the Nobel
      Prize Assembly in its press release of 13 October 1986, "a fascinating example of
      how a skilled observer can create a concept out of apparent chaos".

PMID- 15246434
TI  - Coagulant selection and sludge conditioning in a slaughterhouse wastewater
      treatment plant.
AB  - Attempts were made in this study to examine the effectiveness of polymer addition
      to the aeration tank effluent prior to sludge flotation as practiced in a
      slaughterhouse wastewater treatment plant. The plant currently uses 10 mg/l of
      polymer prior to sludge flotation, but alternative, less-expensive, chemicals
      such as alum could be equally effective. Therefore, experiments were conducted
      using the Standard Jar test to determine the performance of both alum
      (Al2SO4.6H2O) and organic polymer. The dosages used for alum ranged between 0 and
      1000 mg/l, whereas polymer dosages varied between 0 and 90 mg/l. The (optimal)
      removal efficiency for suspended solids in the mixed liquor was obtained at 400
      mg/l for alum and 30 mg/l for polymer. It is evident that addition of alum or
      polymer results in significant removal of suspended solids reaching up to 99% for
      alum and 96% for polymer but alum produced a more compacted sludge. Removal of
      filterable COD was much lower in both cases since the chemicals used target the
      colloidal and suspended portion of the COD rather than the soluble (filterable)
      part of the COD.

PMID- 15246435
TI  - Aerobic composting of chips from clear-cut trees with various co-materials.
AB  - Swollen chips made from trees felled during clear-cutting were composted with
      various organic and inorganic materials in an aerobic composting reactor for 5
      months and then piled for 5 months. The organic materials included chicken feces,
      urea, nitrogenous lime (calcium cyanamide, manure), and material rapidly
      composted from food garbage in 24-h bacterial fermentation, while the inorganic
      materials were coal ash and volcanic ash. In this paper, we first attempt to
      estimate the quality and degree of maturity of each compost from its chemical
      properties. Furthermore, we try to calculate the maturity of the fermented wood
      chip composts from their mixture ratio of the initial materials by multiple
      linear regression analysis. We measured changes in the C/N ratio, nitrate
      nitrogen (NO3-N) content, percentage of humic acid in the alkali soluble fraction
      (PQ), cation exchange capacity, pH, and EC during the composting period. The
      degrees of maturity of the composts were estimated via a plant growth test using
      Chinese cabbage. We found that the CN ratio, NO3-N concentration, and PQ were
      suitable for estimating the degree of maturity of wood chip composts. For
      maturity, the CN ratio should be less than 14, the PQ more than 66.2, and the NO3
      N concentration more than 853 mgkg-1. We devised an equation to estimate the
      degree of maturity after 10 months by a multiple linear regression analysis from
      the mixing ratio of wood chips and the co-composted materials. From the multiple
      linear regression analysis, the above three indices of compost maturity could be
      estimated from the mixing ratio of the initial materials. This equation should
      enable us to determine the degree of compost maturity after 10 months based on
      the initial mixing ratio.

PMID- 15246436
TI  - Termite feeding deterrent from Japanese larch wood.
AB  - Extraction of flavonoids from Japanese larch (Larix leptolepis) wood with water
      was carried out to prepare a termite feeding deterrent. A two-stage procedure for
      the extraction was adopted. The first extraction step was performed at ambient
      temperature (22 degrees C) and the second at elevated temperatures ranging 50-100
      degrees C. The first step mainly gave a mixture of polysaccharides together with
      small amount of flavonoids. At the second step, the yield of extract and its
      chemical composition were greatly affected by the temperature. The yield of
      solubilised carbohydrates steadily increased with a rise in the temperature,
      while the overall yield of flavonoids reached its optimum at 70 degrees C. An
      additional increase in the temperature resulted in a decrease in the yield. Model
      experiments using dihydroflavonols confirmed the occurrence of oxidative
      dehydrogenation and/or intramolecular rearrangement during the hydrothermal
      treatment at higher temperatures. The crude water extracts showed strong feeding
      deterrent activities against the subterranean termite, Coptotermes formosanus, in
      a choice paper disc assay. The extracts containing flavonoids in large quantities
      exhibited potent termite feeding deterrent activities.

PMID- 15246437
TI  - Anaerobic ponds treatment of starch wastewater: case study in Thailand.
AB  - Anaerobic ponds are particularly effective in treating high-strength wastewater
      containing biodegradable solids as they achieve the dual purpose of particulate
      settlement and organic removal. Performance of an anaerobic pond system for
      treatment of starch wastewater containing high organic carbon, biodegradable
      starch particulate matter and cyanide was assessed under tropical climate
      conditions. Approximately 5000 m3/d of wastewater from starch industry was
      treated in a series of anaerobic ponds with a total area of 7.39 ha followed by
      facultative ponds with an area of 29.11 ha. Overall COD and TSS removal of over
      90% and CN removal of 51% was observed. Active biomass obtained from the
      anaerobic ponds sediments and bulk liquid layer exhibited specific methanogenic
      activity of 20.7 and 11.3 ml CH4/g VSS d, respectively. The cyanide degradability
      of sludge at initial cyanide concentration of 10 and 20 mg/l were determined to
      be 0.43 and 0.84 mg CN-/g VSS d, respectively. A separate settling column
      experiment with starch wastewater revealed that a settling time of approximately
      120 min is sufficient to remove 90-95% of the influent TSS.

PMID- 15246438
TI  - Low pH as an inhibiting factor in the transition from mesophilic to thermophilic
      phase in composting.
AB  - During composting of household waste, the acidity of the material affects the
      process during the initial phase of rising temperature. In this study, the
      effects of temperature (36-46 degrees C) and pH (4.6-9.2) on the respiration rate
      during the early phase of composting were investigated in two different composts.
      A respiration method where small compost samples were incubated at constant
      temperature was used. The respiration rate was strongly reduced at 46 degrees C
      and pH below 6, compared to composts with a higher pH or lower temperature. The
      combination of high temperature and low pH is a possible adverse factor in large
      scale composting of food waste.

PMID- 15246439
TI  - Characteristics of anaerobic ammonia removal by a mixed culture of hydrogen
      producing photosynthetic bacteria.
AB  - It is known that the presence of ammonia inhibits hydrogen production by
      photosynthetic bacteria. In order to avoid it, a two-step process containing
      ammonia removal and hydrogen production was investigated in this study. Firstly,
      the effects of carbonate presence on ammonia removal by photosynthetic bacteria
      were investigated by the vial tests because it is known that the uptake of
      volatile fatty acids (VFAs) sometimes requires carbonate. The results of them
      showed that the presence of carbonate promoted the uptake of VFAs and ammonia.
      Especially, the uptake of propionate and/or butyrate required the presence of
      carbonate. The results of the batch experiments of two-step hydrogen production
      showed that the depletion of ammonia triggered hydrogen evolution. Herein, the
      presence of albumin did not inhibit hydrogen evolution and preferably it
      increased the hydrogen production rate. And the VFA-C/NH4-N ratio in substrate
      fed into two-step hydrogen production process should be more than 6.0.

PMID- 15246440
TI  - Seasonal evolution of heavy metal concentrations in the surface sediments of two
      Mediterranean Zostera marina L. beds at Thau lagoon (France) and Venice lagoon
      (Italy).
AB  - The concentrations and the seasonal changes of heavy metals and organic carbon in
      the sediments underlying a Zostera marina L. bed were measured monthly during one
      year, in two Mediterranean lagoons: Thau (France) and Venice (Italy). While at
      Thau sediments showed Cu (18.7+/-3.9 microg g-1) and Pb (13.8+/-3.8 microg g-1)
      average concentrations twofold higher than at Venice (Cu: 8.4+/-4.8 microg g-1;
      Pb: 6.1+/-0.70 microg g-1), the Italian site exhibited average concentrations of
      Fe (13383+/-955 microg g-1 versus 6098+/-1089 microg g-1 at Thau), Mn (339+/-12
      microg g-1 versus 190+/-23 microg g-1 at Thau), Zn (61.6+/-12.7 microgg -1 versus
      36.1+/-7.4 microg g-1 at Thau), Cr (47.3+/-7.3 microg g-1 versus 21.8+/-8.0
      microg g-1 at Thau) and Ni (12.7+/-1.7 microg g-1 versus 8.9+/-3.1 microg g-1 at
      Thau) approximately 1.5-2 times as high as the French site. The organic carbon
      concentration was systematically higher at Thau (1.0+/-0.3) than at Venice (0.7+/
      0.2). A significant seasonal fluctuation was found for Zn, Cu, Ni, Cr in both
      lagoons while no significant variations were recorded for Pb at Venice and for Cd
      at Thau. Some of those changes appeared to be significantly correlated with the
      biomass of Zostera at Thau and the concentration of organic carbon at Venice.

PMID- 15246441
TI  - Predatory efficiency of the water bug Sphaerodema annulatum on mosquito larvae
      (Culex quinquefasciatus) and its effect on the adult emergence.
AB  - The daily number of IV instar larva of Culex quinquefasciatus killed, rate of
      pupation and adult emergence was noted in presence of the predatory water bug
      Sphaerodema annulatum for a period of seven consecutive days, experimentally, in
      the laboratory. The rate of IV instar larva killed by the water bugs on an
      average was 65.17 per day. The rate of pupation ranged between 7.6 and 48 in
      control while in presence of water bugs it ranged between 6 and 35. The rate of
      adult emergence in control experiments varied between 1.4 and 4.8 per day, which
      was reduced to only 0.4-28.8 per day in case of the water bugs. The results
      clearly indicate that the water bugs on its way of predation reduces the rate of
      pupation and adult emergence of Cx. quinquefasciatus significantly which calls
      for an extensive field trials.

PMID- 15246442
TI  - Bioenergy conversion studies of organic fraction of MSW: kinetic studies and gas
      yield--organic loading relationships for process optimisation.
AB  - Batch digestion of municipal garbage was carried out for 100 days at room
      temperature (26+/-4 degrees C; average temperature 25 degrees C) and at ambient
      temperature (32+/-10 degrees C; average temperature 29 degrees C) conditions for
      total solids concentrations varying between 45 and 135 g/l. A first order model
      based on the availability of substrate as the limiting factor was used to perform
      the kinetic studies of batch anaerobic digestion system. Effect of organic solids
      concentration and digestion time on biogas yield was studied and mass and energy
      balance analysis was conducted for batch digestion. The net bioenergy yield from
      municipal garbage and corresponding bioprocess conversion efficiency over the
      length of the digestion time were observed to be 12,528 kJ/kg volatile solids and
      84.51% respectively. The methane content of the biogas generated from the
      reactors was in the range of 62-72% with the overall average methane content of
      the biogas, computed over the total digestion period was 65 vol%.

PMID- 15246443
TI  - Evaluation of fly ash as a carrier for diazotrophs and phosphobacteria.
AB  - Fly ash and its different combinations with soil (w/w) were tested to explore its
      possible use as a potential carrier for diazotrophs and phosphobacteria.
      Azotobacter chroococcum, Azospirillum brasilense and Bacillus circulans showed
      their maximum viability in fly ash alone whereas Pseudomonas striata proliferated
      most in soil:fly ash (1:1) combination.

PMID- 15246444
TI  - Effect of temperature and temperature fluctuation on thermophilic anaerobic
      digestion of cattle manure.
AB  - The influence of temperature, 50 and 60 degrees C, at hydraulic retention times
      (HRTs) of 20 and 10 days, on the performance of anaerobic digestion of cow manure
      has been investigated in completely stirred tank reactors (CSTRs). Furthermore,
      the effect of both daily downward and daily upward temperature fluctuations has
      been studied. In the daily downward temperature fluctuation regime the
      temperatures of each reactor was reduced by 10 degrees C for 10 h while in the
      daily upward fluctuation regime the temperature of each reactor was increased 10
      degrees C for 5 h. The results show that the methane production rate at 60
      degrees C is lower than that at 50 degrees C at all experimental conditions of
      imposed HRT except when downward temperature fluctuations were applied at an HRT
      of 10 days. It also was found that the free ammonia concentration not only
      affects the acetate-utilising bacteria but also the hydrolysis and acidification
      process. The upward temperature fluctuation affects the maximum specific
      methanogenesis activity more severely as compared to imposed downward temperature
      fluctuations. The results clearly reveal the possibility of using available solar
      energy at daytime to heat up the reactor(s) without the need of heat storage
      during nights, especially at an operational temperature of 50 degrees C and at a
      20 days HRT, and without the jeopardising of the overheating.

PMID- 15246445
TI  - Composting winery waste: sludges and grape stalks.
AB  - The composting of winery waste is an alternative to the traditional disposal of
      residues, and also involves a commitment to reducing the production of waste
      products. We studied two residues (sludge and grape stalks), mixed in two
      proportions (1:1 and 1:2 sludge and grape stalks (v/v)), and we also examined the
      effects of grinding the grape stalks. Our results showed that composting the
      assayed materials was possible. Best results were obtained in the compost heap in
      which the residues were mixed in the proportion 1:2, and where the grape stalks
      had been previously ground. Optimum results required a moisture around 55% and a
      maximum temperature around 65 degrees C and an oxygen concentration not lower
      than 5-10%. The resulting compost had a high agronomic value and is particularly
      suitable for the soils of the vineyards which have a very low organic matter
      content. The compost can be reintroduced into the production system, thereby
      closing the residual material cycle.

PMID- 15246446
TI  - Biofilm morphology and nitrification activities: recovery of nitrifying biofilm
      particles covered with heterotrophic outgrowth.
AB  - Biofilm processes are commonly used for nitrification. Operationally, a whitish
      heterotrophic biofilm layer tends to develop onto nitrifying biofilm when it has
      been exposed to organic carbon-containing wastewater for a prolonged period. The
      development of a heterotrophic biofilm layer could lead to deterioration in
      nitrification activities and biofilm morphology. The recovery characteristics, in
      terms of biofilm morphology and nitrification activities, of deteriorated biofilm
      particles (i.e. nitrifying biofilm particles covered with heterotrophic
      outgrowth) were investigated by transferring the deteriorated biofilm particles
      (from an Ultra-Compact Biofilm Reactor (UCBR) which was part of a packed bed-UCBR
      system used for treating organic carbon and ammonia-containing wastewater) to a
      UCBR fed solely with ammonia wastewater (referred to as 'Recovery-UCBR'). At a
      hydraulic retention time (HRT) of 8.7 h and a sand-carrier concentration of 4.0%
      (v/v), density of the outer heterotrophic biofilm layer reduced progressively
      which led to subsequent detachment of this layer from the nitrifying biofilm
      particles. As a result, morphology of the nitrifying biofilm improved gradually
      in the Recovery-UCBR. A stable nitrification rate of up to 1.74 kg NH4+-N/m3 d
      was obtained in the Recovery-UCBR.

PMID- 15246447
TI  - Influence of the stabilisation of organic materials on their biopesticide effect
      in soils.
AB  - Some organic materials have shown a suppressive effect on several diseases
      induced by soilborne plant pathogens. We have carried out a laboratory experiment
      (microcosm) to ascertain the influence of the stabilisation process of sewage
      sludge on it biopesticide effect when Pythium ultimum or Phytophthora sp. were
      introduced to soil as pathogens for pea or pepper. When P. ultimum was introduced
      there was a 63.8% reduction in the weight of the stems grown in the control,
      47.6% in the presence of sewage sludge, but only 24.7% with compost. The same
      biopesticide effect was evident from the weight of the roots. The biopesticide
      effect was also strong when compost was used as organic amendment in the presence
      of Phytophthora, as could be seen from stem and shoot weight and length. The data
      showed that the degree of stabilisation of the organic material (compost) had a
      positive influence on it biopesticide effect. The changes undergone by a soil
      after the addition of organic materials helped to explain the biopesticide effect
      of the amendment. The organic treatments reduced P. ultimum and Phytophthora sp.
      populations.

PMID- 15246448
TI  - Effects of plant growth promoting bacteria and composed organic fertilizers on
      the reproduction of Meloidogyne incognita and tomato growth.
AB  - Glasshouse experiments were conducted to assess the influence of Pseudomonas
      fluorescens, Azotobacter chroococcum, Azospirillum brasilense and composted
      organic fertilizers (cow dung, horse dung, goat dung and poultry manure) alone
      and in combination on the multiplication of Meloidogyne incognita and growth of
      tomato. P. fluorescens was better at improving tomato growth and reducing galling
      and nematode multiplication than A. chroococcum or A. brasilense. Among composted
      organic fertilizers, poultry manure resulted in less galling and nematode
      multiplication than occurred with goat dung. However, composted goat dung was
      better in reducing nematode multiplication and improving plant growth than horse
      dung. Cow dung was the composted organic fertilizer least effective in reducing
      galling and nematode multiplication. Poultry manure with P. fluorescens was the
      best combination for the management of M. incognita on tomato but improved
      management of M. incognita can also be obtained if goat dung is used with P.
      fluorescens or poultry manure with A. chroococcum.

PMID- 15246449
TI  - Antioxidant activity of leaf extracts from Bauhinia monandra.
AB  - Bauhinia monandra Kurz. is used in Brazil for the treatment of diabetes. Since
      this activity may be correlated with the presence of antioxidant compounds, leaf
      extracts of B. monandra were evaluated for their radical scavenging capacity
      (RSC). An ethanolic extract was taken up in aqueous methanol and partitioned with
      hexane, chloroform, ethyl acetate to yield three organic extracts together with
      remaining aqueous extract. The RSC was determined spectrophotometrically using
      1,1-diphenylpicrylhydrazyl free radical (DPPH). The chloroform and ethyl acetate
      extracts were the most appropriate as sources of antioxidant compounds as shown
      by their inhibition concentration (IC50) and inhibition percentage (IP) values.
      The antioxidant activity of such extracts was attributed to the presence of three
      compounds of different polarities (flavonoids and steroids). The chloroform and
      ethyl acetate extracts exhibited an IC50 of approximately 2 mg/g DPPH and IP
      values in the range of 60-65%. The results indicate that the extracts of B.
      monandra have a very potent antioxidant activity, compared with the pure
      catechins used as positive controls and with other plant extracts.

PMID- 15246450
TI  - Lateral visual field stimulation reveals extrastriate cortical activation in the
      contralateral hemisphere: an fMRI study.
AB  - We examined whether lateral visual field stimulation (LSTM) could activate
      contralateral extrastriate cortical areas as predicted by a large experimental
      literature. We asked seven unscreened, control subjects to wear glasses designed
      to allow vision out of either the left (LVF) or right lateral visual field (RVF)
      depending upon which side the subject looked toward. Each subject participated in
      a block design functional magnetic resonance imaging (fMRI) study with
      alternating 30-s epochs in which he was asked to look to one side and then the
      other for a total of five epochs. On each side of the bore of the scanner, we
      taped a photograph for the subject to view in the LVF and RVF. The data were
      analyzed with SPM99 using a fixed effect, box-car design with contrasts for the
      LVF and the RVF conditions. Both LVF and RVF conditions produced the strongest
      fMRI activation in the contralateral occipitotemporal and posterior parietal
      areas as well as the contralateral dorsolateral prefrontal cortex. LSTM appears
      to increase contralateral fMRI activation in striate and extrastriate cortical
      areas as predicted by earlier studies reporting differential cognitive and/or
      emotional effects from unilateral sensory or motor stimulation.

PMID- 15246451
TI  - Effects of citalopram on worry and brain activation in patients with generalized
      anxiety disorder.
AB  - The effects of auditory statements describing a personal worry on brain
      activation as measured by functional magnetic resonance imaging were examined in
      patients with generalized anxiety disorder (GAD) before and after anxiety
      reduction with citalopram. Six patients were imaged while listening to verbal
      descriptions of a personal worry or a neutral statement before treatment with
      citalopram and after 7 weeks of treatment. Pre-post drug analyses showed
      treatment with citalopram reduced self-reported anxiety and reduced BOLD
      responses to a pathology-specific worry and a neutral stimulus. After treatment,
      worry sentences, compared to neutral statements, elicit reduced BOLD responses in
      prefrontal regions, the striatum, insula and paralimbic regions. In addition,
      contrasts before and after treatment revealed reductions in the differential
      response that existed between worry and neutral statements. Overall reduction of
      BOLD response was most prominent during neutral statements, particularly in the
      left hemisphere. These findings support the clinical impression that GAD patients
      overreact to both pathology-specific and non-specific cues and that the reduction
      of anxiety attenuates the response to both types of cues.

PMID- 15246452
TI  - Functional MRI study of a serial reaction time task in Huntington's disease.
AB  - The aim of this study was to investigate pathophysiological changes at an early
      stage of clinical Huntington's disease (HD) using a functional magnetic resonance
      imaging (fMRI) study and a serial reaction time task paradigm. Mildly affected
      and presymptomatic HD subjects (n = 8) and healthy normal controls (NC, n = 12)
      were studied. A group behavioral effect of implicit learning was seen only in the
      control population. Individual statistical parametric mapping (SPM) analysis
      showed more consistent activation of the caudate nucleus and putamen in the NC
      group. In the HD group, the group average SPM showed significant activation in
      the right head of caudate nucleus, as well as bilateral thalami, left middle
      temporal, right superior temporal, right superior frontal, right middle and
      inferior frontal and right postcentral gyri. In the comparison of between-group
      differences (NC-HD), reduced activation in the HD group relative to NC was
      observed in the right middle frontal, left middle occipital, left precuneus, and
      left middle frontal gyri. The variable striatal activity in the Huntington's
      group suggests early functional loss possibly associated with previously
      demonstrated early atrophy of these same neural structures.

PMID- 15246453
TI  - Neural correlates of action attribution in schizophrenia.
AB  - Patients with first-rank symptoms (FRS) of schizophrenia do not experience all of
      their actions and personal states as their own. FRS may be associated with an
      impaired ability to correctly attribute an action to its origin. In the present
      study, we examined regional cerebral blood flow (rCBF) with positron emission
      tomography during an action-attribution task in a group of patients with FRS. We
      used a device previously used with healthy subjects that allows the experimenter
      to modulate the subject's degree of movement control (and thus action
      attribution) of a virtual hand presented on a screen. In healthy subjects, the
      activity of the right angular gyrus and the insula cortex appeared to be
      modulated by the subject's degree of movement control of the virtual hand. In the
      present study, the schizophrenic patients did not show this pattern. We found an
      aberrant relationship between the subject's degree of control of the movements
      and rCBF in the right angular gyrus and no modulation in the insular cortex. The
      implications of these results for understanding pathological conditions such as
      schizophrenia are discussed.

PMID- 15246454
TI  - Lower prefrontal gray matter volume in schizophrenia in chronic but not in first
      episode schizophrenia patients.
AB  - Although a lower volume of prefrontal (PF) gray matter (GM) in patients with
      schizophrenia than in normal control subjects is a replicated finding, it is not
      yet clear whether this finding is present at the onset of illness. Clinical and
      imaging data suggest that the reduction in PF GM becomes apparent only some years
      following the onset of illness. To test this hypothesis, we used magnetic
      resonance imaging to study PF GM and sulcal cerebrospinal fluid (CSF) volumes in
      81 schizophrenic patients. A Talairach-based tool was used for segmentation.
      Subjects included 44 healthy controls, 22 first-episode (FE), treatment-naive
      patients with duration of illness of less than 1 year; 29 short-term chronic (SC)
      patients with durations of illness between 1.5 and 6 years; and 30 long-term
      chronic (LC) patients with duration of illness of more than 6 years. The data
      from healthy controls were used to calculate volume residuals in the patients,
      defined as deviations from the expected values given individual age and
      intracranial volume. The FE group did not show significant differences in GM or
      in CSF volumes compared with controls. However, both the SC and the LC patients
      showed the expected pattern of lower values for PF GM and an excess of PF sulcal
      CSF compared with controls. There were no significant differences between SC and
      LC patients in any of these measurements. There was a significant and inverse
      association between duration of illness and GM residuals. That association fit a
      nonlinear rather than a linear model, which was consistent with a decrease of GM
      volume during the first years following illness onset. No significant differences
      were found between those receiving atypical and typical antipsychotic drugs
      during the previous year.

PMID- 15246455
TI  - Voxel-based morphometry in adolescents with bipolar disorder: first results.
AB  - Bipolar disorder is an increasingly recognized cause of significant morbidity in
      the pediatric age group. However, there is still a large degree of uncertainty
      regarding the underlying neurobiological deficits. In this preliminary study, we
      performed automated volumetric studies and whole-brain voxel-based morphometry
      (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were
      compared with data from 52 age- and gender-matched healthy controls. Previously
      defined brain parcellations and optimized VBM protocols were used, based on
      custom-made pediatric reference data. An additional, exploratory whole-brain
      comparison was also implemented. The volumetric region-of-interest study revealed
      significantly greater gray matter volume in central gray matter structures
      bilaterally (including the basal ganglia and the thalamus) and the left temporal
      lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia.
      Localized gray matter deficits in bipolar subjects were found in the medial
      temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and
      extending earlier studies.

PMID- 15246456
TI  - Volumes of the caudate nuclei in women with somatization disorder and healthy
      women.
AB  - Very little is known about the pathophysiology of somatization disorder. This
      study was designed to analyze the volumes of some brain structures possibly
      involved in somatization based on the observation of glucose metabolism of the
      brain in these patients. We studied 10 female patients with a diagnosis of
      somatization disorder or undifferentiated somatoform disorder with no comorbid
      current DSM-IV Axis I disorder and compared them to 16 healthy female volunteers
      using brain MRI (1.5 T instrument). The patients had bilateral enlargement of
      caudate nuclei volumes compared with healthy volunteers. These volume differences
      in the caudate nuclei could be associated with the pathophysiology of
      somatization.

PMID- 15246457
TI  - Dimensional complexity of the EEG in patients with posttraumatic stress disorder.
AB  - Recent electrophysiological studies have reported evidence of information
      processing abnormalities in patients with posttraumatic stress disorder (PTSD).
      The aim of this study is to examine dynamical complexity of the EEG in PTSD
      patients, which is thought to reflect information processing of the brain.
      Resting EEG recordings (32,800 data points acquired continuously from 82 s of an
      EEG record) were obtained in 16 channels of 27 patients with PTSD from a mixed
      civilian trauma population and 14 healthy subjects. The correlation dimension
      (D2) of the EEG was used to quantify the complexity of the cortical dynamics
      underlying the EEG signal. The PTSD patients were found to have lower D2 values
      than those of the healthy subjects in most channels (Fp1, F8, C4, P4, T3, T4, T5,
      T6, and O1), indicating that PTSD patients have globally reduced complexity in
      their EEG waveforms. This study supports the hypotheses that PTSD patients
      exhibit disturbed cortical information processing, and that non-linear dynamical
      analysis of the EEG can be a tool for detecting changes in neurodynamics of the
      brain in PTSD.

PMID- 15246458
TI  - The effects of antipsychotic therapy on serum lipids: a comprehensive review.
AB  - OBJECTIVES: The purpose of this paper is to review the literature since 1970
      documenting the effects of antipsychotic agents on serum lipids, including a
      discussion of possible mechanisms for the observed phenomena, the clinical
      significance and recommendations for monitoring hyperlipidemia during
      antipsychotic therapy. RESULTS: High-potency conventional antipsychotics (e.g.,
      haloperidol) and the atypical antipsychotics, ziprasidone, risperidone and
      aripiprazole, appear to be associated with lower risk of hyperlipidemia. Low
      potency conventional antipsychotics (e.g., chlorpormazine, thioridazine) and the
      atypical antipsychotics, quetiapine, olanzapine and clozapine, are associated
      with higher risk of hyperlipidemia. Possible hypotheses for lipid dysregulation
      include weight gain, dietary changes and the development of glucose intolerance.
      CONCLUSIONS: Given the multiple cardiovascular risk factors seen in patients with
      schizophrenia, great care must be exercised in the choice of antipsychotic
      therapy to minimize the medical burden of additional risk imposed by
      hyperlipidemia. It is recommended that a lipid panel be obtained at baseline in
      all patients with schizophrenia, annually thereafter for patients on agents
      associated with lower risk of hyperlipidemia and quarterly in patients on agents
      associated with higher risk for hyperlipidemia. All patients with persistent
      dyslipidemia should be referred for lipid-lowering therapy or switched to a less
      lipid-offending antipsychotic agent.

PMID- 15246459
TI  - Abnormal neurological signs at the onset of psychosis.
AB  - INTRODUCTION: The objective of this investigation was to determine whether
      abnormal neurological signs (ANS) are present at the onset of psychosis, prior to
      the initiation of antipsychotic treatment, and to examine the effect of 6 weeks
      of antipsychotic treatment on these signs. METHODS: We examined 29 first-episode
      schizophrenic patients admitted at an Army Medical Center within 10 days of
      psychosis onset, using the Neurological Evaluation Scale and the 18-item Brief
      Psychiatric Rating Scale (BPRS) and compared them to controls. RESULTS: All of
      the subjects had neurological signs indicating problems in sensory integration,
      motor coordination, and sequencing of complex motor acts. No psychotic subject
      had fewer than two abnormal neurological signs. When compared to age and sex
      matched groups of normal controls and nonpsychotic psychiatric controls, the
      psychotic group had a significantly higher incidence of neurological signs. At
      baseline, the severity of neurological signs was associated with elevated BPRS
      total, positive, and negative symptom scores. The change in clinical symptoms was
      positively correlated with a change in neurological signs. DISCUSSION: These
      findings indicate that some neurological signs are present at the onset of
      psychosis, and that these signs may be altered by treatment. These abnormal
      neurological signs reflect an underlying brain function abnormality and may be
      useful in differential diagnosis, prognosis, and treatment selection.

PMID- 15246460
TI  - Effects of acute metabolic stress on the dopaminergic and pituitary-adrenal axis
      activity in patients with schizotypal personality disorder.
AB  - BACKGROUND: Stress has been associated with the onset of schizophrenia and
      exacerbation of psychotic symptoms. Patients with schizotypal personality
      disorder (SPD), the prototypic schizophrenia spectrum disorder, do not develop
      the frank psychosis of schizophrenia and appear clinically to be less reactive to
      stress than schizophrenic patients. Schizophrenic patients demonstrate increased
      dopaminergic (DA) and hypothalamic-pituitary-adrenal-axis (HPA) activation
      following 2-deoxyglucose (2-DG), an acute metabolic (glycopyruvic) stressor,
      compared to healthy volunteers (HV). We hypothesized that SPD patients would
      demonstrate comparable or lower DA and HPA responses after 2-DG to HV. METHODS:
      Fifteen SPD patients and 13 HV were administered 2-DG (40 mg/kg, i.v.) in a
      double-blind, placebo-controlled, randomized protocol. The area under the curve
      (AUC) was determined for plasma HVA, ACTH and cortisol (utilizing baseline and
      post infusion indices). RESULTS: 2-DG induced significant increases in ACTH,
      cortisol and HVA concentrations in both groups and cortisol elevations were
      significantly lower in patients with SPD than in HV. CONCLUSIONS: Patients with
      SPD have a blunted cortisol and a normal dopaminergic response to 2-DG. These
      results are consistent with the hypothesis that SPD patients are better buffered
      against DA and HPA overactivation in response to stress.

PMID- 15246461
TI  - Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review
      of randomized trials.
AB  - Randomized controlled trials comparing valproate (as a sole, or as an adjunctive
      compound) to placebo for patients with schizophrenia or schizophrenia-like
      disorders were summarized in a metaanalysis. It was possible to include only five
      trials (n = 379) examining valproate as add-on to antipsychotics in this review.
      Some of the single studies showed inconsistent beneficial effects on some aspects
      of response, but no overall superiority of valproate augmentation at study
      endpoints was shown.

PMID- 15246462
TI  - Health and development in the first 4 years of life in offspring of women with
      schizophrenia and affective psychoses: Well-Baby Clinic information.
AB  - The investigation of genetic high-risk (HR) groups provides the opportunity to
      study diathesis characteristics associated with schizophrenia (Sc) and affective
      psychoses. High-risk offspring of women with a history of schizophrenia,
      affective and other psychoses (n = 84), as well as normal-risk control (NC)
      offspring (n = 100), were studied from 0 to 4 years of age, using prospectively
      recorded information from Well-Baby Clinic (WBC) records. Blind assessment of an
      average of 25 contacts per subject yielded data concerning early life
      developmental, physical and behavioral characteristics associated with psychosis
      risk. As compared with controls, offspring of women with schizophrenia showed
      significantly increased rates of delayed walking, visual dysfunction, language
      skill disorders, enuresis, disturbed behavior (especially poor social
      competence), and multiple accumulated risk characteristics. Significant Sc-risk
      characteristics did not include impaired hearing, minor malformations, biological
      dysfunctions, or physical illness leading to treatment. Offspring of mothers with
      affective psychosis (Aff) showed only a significantly increased rate of delayed
      walking, with no significantly increased total aggregation of risk
      characteristics, compared with controls. The results suggest a limited overlap in
      the diathesis characteristics associated with risk for Sc vs. Aff psychosis. The
      importance of these early risk characteristics for the later development of
      psychopathology is being investigated in this sample.

PMID- 15246463
TI  - Association between short birth intervals and schizophrenia in the offspring.
AB  - Pregnancy burdens maternal folate reserves. Postpartum restoration to normal
      folate values may take up to 1 year. Maternal folate deficiency during early
      pregnancy has been hypothesized as a cause of schizophrenia in the offspring. We
      investigated whether the risk of schizophrenia is increased in persons conceived
      shortly after another birth. A population-based cohort was established of 1.43
      million persons born in Denmark between 1950 and 1983, yielding 17.6 million
      person-years of follow-up. Schizophrenia in cohort members (5095 cases) and their
      siblings and parents was identified by linkage with the Danish Psychiatric Case
      Register. Relative risks of schizophrenia were estimated by use of log-linear
      Poisson regression. As compared to intervals of 45 months and longer, the
      schizophrenia risk ratio was 1.14 (95% confidence interval [CI], 0.97 to 1.35)
      for interbirth intervals of up to 15 months, 1.32 (95% CI, 1.12 to 1.56) for
      intervals of 15 to 17 months, 1.38 (95% CI, 1.18 to 1.61), for intervals of 18 to
      20 months and 1.13 (95% CI, 1.00 to 1.29) for intervals of 21 to 26 months.
      Relative risks did not essentially change after adjustment for age, sex, calendar
      year of diagnosis, maternal and paternal age, history of mental illness in a
      parent or sibling, sibship size, place of birth, and distance to younger sibling.
      These results show an association between short birth intervals and schizophrenia
      in the offspring. Although maternal folate depletion may play a role in this
      association, we cannot rule out other explanations such as maternal stress during
      pregnancy and childhood infections.

PMID- 15246464
TI  - Weight decline in patients switching from olanzapine to quetiapine.
AB  - This open-label study investigated the strategy of switching patients who had
      gained excessive weight on olanzapine to quetiapine, with assessments of safety
      and continued efficacy as well as weight change. Patients who were
      psychiatrically stable on olanzapine but had gained >20% in weight and had body
      mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and
      followed for 6 weeks, the total study duration being 10 weeks. Assessments
      included weight change, antipsychotic efficacy using the Positive and Negative
      Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson
      Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled
      patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohen's d = 0.12;
      P = 0.03). There were no significant changes in PANSS total scores, SAS scores,
      or metabolic parameters. Switching patients to quetiapine, appears to be a viable
      strategy for managing olanzapine-induced weight gain as indicated by this 10-week
      open-label study. Prospective controlled trials of longer duration and larger
      number of subjects are needed.

PMID- 15246465
TI  - Body weight, image and self-esteem evaluation questionnaire: development and
      validation of a new scale.
AB  - This report describes the development of a new questionnaire designed to capture
      and quantify the psychosocial impact of weight gain associated with psychotropic
      drug use, and presents results of a preliminary validation study. Based on a
      review of literature, consultations with experts, interviews with individual
      patients and focus groups, themes relevant to weight gain and its psychosocial
      consequences were identified. A 12-item self-report questionnaire was designed
      and administered to a heterogeneous group of psychiatric outpatients (n = 141)
      receiving antipsychotic and other adjunctive medications. The scale could be self
      administered in 2-3 min with minimal assistance. Correlational analysis showed a
      high internal consistency (Cronbach's alpha 0.79) and fair split half reliability
      (Spearman-Brown coefficient of 0.76). The total scores were able to distinguish
      groups of people with higher and lower body mass index (BMI) (chi(2) = 16.4, p <
      0.001), suggestive of good discriminant validity. Repeated administration of the
      scale in 56 subjects on 2 occasions with a gap of 1 week in between revealed a
      test-retest reliability coefficient of 0.81 (p < 0.001). These preliminary
      findings indicate that body weight, image and self-esteem evaluation
      questionnaire (B-WISE) is a potentially useful instrument for clinical trials to
      measure the psychosocial consequences of weight changes associated with
      psychotropic drug use, and also in monitoring the impact of various intervention
      programs aimed at minimizing or preventing weight gain.

PMID- 15246466
TI  - Effects of typical and atypical antipsychotic drugs on maternal behavior in
      postpartum female rats.
AB  - Understanding the effects of antipsychotic drugs (APDs) on social behaviors such
      as maternal behavior is valuable for understanding the complete spectrum of
      therapeutic and side-effects of antipsychotics. Although previous studies have
      suggested that typical antipsychotics impair maternal behavior, the effects of
      the atypical antipsychotics have not been systematically explored. The purpose of
      the present report was to examine the effects of typical (haloperidol, HAL) and
      several atypical (clozapine, CLZ; risperidone, RIS; quetiapine, QUE)
      antipsychotics on maternal behavior in female rats. Maternal behaviors were
      examined repeatedly over a period of 24 h after a single injection of a range of
      doses of HAL, CLZ, RIS or QUE on Day 6 postpartum. All antipsychotic drugs,
      typical or atypical, elicited a qualitatively similar disruptive effect on the
      active components of maternal behavior such as pup approach, pup retrieval and
      nest building at clinically relevant doses. However, HAL caused a prolonged
      disruption, whereas CLZ, RIS and QUE induced an early onset but shorter duration
      disruption. In addition, only the atypical antipsychotics showed some inhibitory
      effects on nursing behavior, possibly due to sedative side-effects shared by all
      atypical antipsychotics. The current generation of atypical antipsychotics shows
      a disruptive influence on maternal behavior similar to that of the typical
      antipsychotics. This effect may be intrinsic to antipsychotic activity or may be
      reflective of a side-effect. Since the latter is more likely, this may be an
      effect to avoid in the design of future antipsychotics.

PMID- 15246467
TI  - Co-administration of atypical antipsychotics and antidepressants disturbs
      contrast detection in schizophrenia.
AB  - Atypical antipsychotics (APDs) antagonize both serotonin and dopamine receptors.
      This antagonism is, however, often confounded by co-administration of other
      medications, such as antidepressants, that affect pharmacological activity at
      these receptors. While it is known that the modulation of dopamine affects
      cognitive processes such as working memory, the interactions between APDs and
      antidepressants in behaviors including sensory processes are not clear. In this
      study, we investigated the effect of combined treatment with antidepressants and
      atypical antipsychotics on memory-related visual processing in schizophrenia. We
      employed (1) contrast detection, a task requiring the maintenance of visual
      signals over a short period of time; and (2) direction discrimination, a task not
      requiring maintenance of visual signals. On contrast detection, the performance
      was significantly worse in the patients taking both APDs and antidepressants than
      in patients taking just APDs. On direction discrimination, however, the
      performance did not differ between the patients tasking just APD and those taking
      both APDs and antidepressants. Given that antidepressants interfere with APD's
      stimulation of D1 receptors via agonism of serotonin receptors, the poor
      performance on contrast detection suggests that the interaction between these two
      types of psychotropic drugs selectively disrupts the sensory processes requiring
      retention of visual information.

PMID- 15246468
TI  - Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia.
AB  - The pharmacokinetics and tolerability of long-acting risperidone (Risperdal
      Consta) were evaluated in a multicenter, prospective, open-label, 15-week study
      of 86 patients with schizophrenia. Subjects stabilized on 2, 4 or 6 mg of oral
      risperidone once daily for at least 4 weeks were assigned to receive i.m.
      injections of 25, 50 or 75 mg of risperidone, respectively, every 2 weeks for 10
      weeks. The 90% confidence intervals for the i.m./oral ratios of the mean steady
      state plasma-AUC, corrected for dosing interval, and of the average plasma
      concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) were
      within the range of 80-125%, indicating bioequivalence of the i.m. and oral
      formulations. However, mean steady-state peak concentrations of the active moiety
      were 25-32% lower with i.m. than oral dosing (P < 0.05) and fluctuations in
      plasma active-moiety levels were 32-42% lower with the i.m. than oral regimen.
      Symptoms of schizophrenia continued to improve after switching from oral to i.m.
      dosing. Long-acting risperidone was well tolerated locally and systematically.
      Although overall bioequivalence of the two formulations was established, the
      differences in pharmacokinetic profiles between the two formulations indicate
      potential benefits for long-acting risperidone.

PMID- 15246469
TI  - Schizophrenia as one extreme of a sexually selected fitness indicator.
AB  - Schizophrenia remains an evolutionary paradox. Its delusions, hallucinations and
      other symptoms begin in adolescence or early adulthood and so devastate sexual
      relationships and reproductive success that selection should have eliminated the
      disorder long ago. Yet it persists as a moderately heritable disorder at a global
      1% prevalence--too high for new mutations at a few genetic loci. We suggest that
      schizophrenia persists and involves many loci because it is the unattractive, low
      fitness extreme of a highly variable mental trait that evolved as a fitness
      ("good genes") indicator through mutual mate choice. Here we show that this
      hypothesis explains many key features of schizophrenia and predicts that some
      families carry modifier alleles that increase the indicator's neurodevelopmental
      sensitivity to heritable fitness and condition. Such alleles increase the extent
      to which high-fitness family members develop impressive courtship abilities and
      achieve high reproductive success, but also increase the extent to which low
      fitness family members develop schizophrenia. Here we introduce this fitness
      indicator model of schizophrenia, discuss its explanatory power, explain how it
      resolves the evolutionary paradox, discuss its implications for gene hunting, and
      identify some empirically testable predictions as directions for further
      research.

PMID- 15246470
TI  - Schizophrenia as one extreme of a sexually selected fitness indicator.

PMID- 15246471
TI  - Schizotypal personality traits and deception: the role of self-awareness.

PMID- 15246472
TI  - Hodgkin's disease: a quantitative evaluation by computed tomography of tumor
      burden.
AB  - A direct method for the evaluation by computed tomography (CT) of the neoplastic
      mass (tumor burden [TB]) has been adopted in 34 patients diagnosed with Hodgkin's
      disease in the early stage. Stressed are its prognostic value, and its
      correlation with the clinical and laboratory parameters usually adopted in the
      staging of the disease and in its follow-up. It is concluded that the CT
      calculated TB is a reliable index showing good correlation with other commonly
      used prognostic parameters.

PMID- 15246473
TI  - An initial experience: using helical CT imaging to detect obscure
      gastrointestinal bleeding.
AB  - Obscure gastrointestinal (GI) bleeding is a common but frustrating disease for
      clinicians because of its elusive nature despite extensive work-up. We evaluate
      the role of helical computed tomography (CT) imaging using rapid infusion of
      intravenous contrast and water as oral contrast in the work-up of patients who
      are actively bleeding. Helical CT may be a useful noninvasive, alternative study
      to consider when routine work-up fails to determine the cause of active GI
      bleeding. Our preliminary study shows that helical CT was able to identify a wide
      variety of causes of obscure GI bleeding.

PMID- 15246474
TI  - Occlusive arterial disease of abdominal aorta and lower extremities: comparison
      of helical CT angiography with transcatheter angiography.
AB  - The purpose of this study was to evaluate helical CT angiography in the
      assessment of occlusive arterial disease of abdominal aorta and the lower
      extremities. Sixteen patients underwent both transcatheter angiography and
      helical CT. Helical CT was inconclusive in 6.2% of segments whereas angiography
      was inconclusive in 5%. The overall sensitivity of helical CT was 91% and
      specificity 93%. Segmental analysis found a sensitivity of 43% in infrapopliteal
      arteries, and a specificity of 86%.

PMID- 15246475
TI  - CNS vasculitis and vasculopathy: efficacy and usefulness of diffusion-weighted
      echoplanar MR imaging.
AB  - This pictorial essay illustrates the usefulness of diffusion-weighted imaging
      (DWI) on various vasculitis or vasculopathies, including systemic lupus
      erythematosus (SLE), Behcet's disease, Churg-Strauss disease, primary angitis of
      the central nervous system (PACNS), giant cell arteritis, infectious vasculitis,
      sickle cell disease, drug-induced vasculopathy and hypertensive vasculopathy. DWI
      proves to detect small and active ischemic changes not visible on conventional
      MRI, and it clearly discriminates cytotoxic from vasogenic edema in patients with
      cerebral vasculitis or vasculopathy. DWI seems useful in assessing the treatment
      and patient outcome.

PMID- 15246476
TI  - Granular cell tumor presenting as an intradural extramedullary tumor.
AB  - Granular cell tumor (GCT) is an uncommon benign tumor, which is thought to
      originate from a Schwann cell. GCT may involve any part of the body, but in our
      knowledge, there has been only one previous report of GCT, which arose in the
      intradural extramedullary space of the spine. We report a case of GCT, which
      occurred in the intradural extramedullary space.

PMID- 15246477
TI  - Thymic MALT lymphoma: MR imaging findings and their correlation with
      histopathological findings on four cases.
AB  - There has been no report on the MRI findings of primary thymic MALT lymphoma. We
      report the correlation between MRI findings and histopathology in four cases of
      this entity. While primary thymic MALT lymphomas exhibited diverse
      characteristics, the cystic components inside, which were clearly depicted on T2
      weighted images, were considered to be pathognomonic. Primary thymic MALT
      lymphoma should be considered as one of the differential diagnoses of anterior
      mediastinal tumors having multilocular cysts that arise in patients with
      immunological abnormalities.

PMID- 15246478
TI  - Breast abscess mimicking malignant mass due to retained penrose drain: diagnosis
      by mammography and MRI.
AB  - We report a breast mass associated with a foreign body mimicking malignancy on
      mammography. Although retained penrose drains have been reported in other parts
      of the body, our case is the first report of a retained penrose drain in breast
      diagnosed by mammography. Mammography can be used if there is suspicion of a
      retained penrose drain during the course of breast abscess treatment.

PMID- 15246479
TI  - Imaging features of atypical thoracic Castleman disease.
AB  - The imaging features of 16 cases of pathologically proven atypical thoracic
      Castleman disease (CD) were retrospectively reviewed. Thirteen out of 16 tumors
      originated from atypical locations, including eight from the pleura and one each
      from the axilla, supraclavicular fossa, intercostal space, pericardium, and lung.
      Six out of 16 tumors revealed atypical enhancement, including poor CT enhancement
      in three tumors, target-like CT enhancement in two tumors, and concentric MR
      enhancement pattern in one tumor. These atypical enhancement patterns were
      histopathologically corresponded to various degrees of degeneration, necrosis,
      and fibrosis.

PMID- 15246480
TI  - Efficacy of transrectal ultrasonography in the evaluation of hematospermia.
AB  - OBJECTIVE: To assess the efficacy of transrectal ultrasonography (TRUS) in the
      evaluation of hematospermia. MATERIAL AND METHODS: This study included 54
      patients with hematospermia. Patients age range was between 25 and 75 years
      (mean=49.7 years). All patients were evaluated by TRUS using a biplane transducer
      and a Toshiba SSA-270A device. RESULTS: TRUS revealed one or more abnormalities
      in 51 patients (94.5%). Prostatic calcifications were found in 23 patients,
      ejaculatory duct calculi in 21, dilated ejaculatory ducts in 18, benign prostatic
      hyperplasia in 18, dilated seminal vesicles in 12, calcifications in seminal
      vesicles in 11, ejaculatory duct cyst in 6, prostatitis in 6, and periurethral
      Cowper gland mass in 1. CONCLUSION: TRUS is a noninvasive, safe method for the
      investigation of causes of hematospermia. We believe that it should be the first
      radiological investigation to be performed in patients presenting with
      hematospermia.

PMID- 15246481
TI  - Imaging findings of extrapulmonary metastases of osteosarcoma.
AB  - PURPOSE: To review imaging findings of extrapulmonary metastasis from
      osteosarcoma and to evaluate them for any consistent pattern and correlation
      between imaging findings. MATERIALS AND METHODS: This study was retrospectively
      conducted in 13 patients with extrapulmonary metastasis of pathologically
      confirmed osteosarcoma. We evaluated the radioisotope (RI) scans (n=16),
      ultrasonography (USG) (n=4), computed tomography (CT) scans (n=10), MRIs (n=6),
      clinical records, and pathological reports for assessment of imaging findings and
      correlation between radiologic findings and RI uptake of the lesions. Points
      evaluated were the following: uptake on RI scans, presence of mineralization on
      CT, and MRI, size, enhancement pattern, attenuation on CT, signal intensity (SI)
      on MRI, and echogenicity on USG. RESULTS: Extrapulmonary metastatic sites were
      diverse, including another bone other than the primary site (n=6), lymph node
      (n=4), pleura (n=2), liver (n=2), pancreas (n=1), kidney (n=1), peritoneum (n=1),
      muscle (n=1), and subcutaneous fat layer (n=1). One patient had tumor growth
      within the pulmonary artery and jejunum. Among 21 metastatic sites in 13
      patients, bone scan was performed in 16 cases and RI uptake was detected in 10
      lesions. Calcification was detected in eight lesions on radiologic imaging,
      including plain radiography, USG, CT, and MRI. Two lesions showed RI uptake
      without definite calcification or ossification on MRI and plain radiography,
      respectively. We analyzed the enhancement pattern and mass size in 18 metastatic
      sites and these factors had poor correlation with uptake on RI scans. CONCLUSION:
      The sites and imaging findings of extrapulmonary metastasis of osteosarcoma were
      variable. All the lesions with mineralization were detectable on RI scans prior
      to radiologic imaging. RI scan has a limited role in the evaluation of metastatic
      lesions without mineralization.

PMID- 15246482
TI  - MR imaging of infiltrative muscle involvement with Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) consists of three clinical syndromes of
      varying severity resulting from basic cellular defect leading to lipid deposition
      within histiocytes. Radiologically, bone lesions are similar in all three forms
      of LCH and are due to bone destruction. An eosinophilic granuloma of the bone can
      involve skeletal muscle by direct extension from the bone. However, skeletal
      muscle involvement is rare and is not reported on MR imaging previously in the
      English literature. Our case not only shows biopsy-proven muscle involvement by
      LCH but also reports the first diffuse nodular pattern of muscle involvement by
      LCH.

PMID- 15246483
TI  - Osteonecrosis in patients with systemic lupus erythematosus: MR imaging and
      scintigraphic evaluation.
AB  - This study was to describe the findings of osteonecrosis in patients with SLE at
      MR and scintigraphic imaging. Among 415 patients with SLE, 37 patients were
      diagnosed to have osteonecrosis. MR images and bone scintigraphs were analyzed
      for sites of involvement, signal intensity, bilaterality and multiplicity. MR
      imaging features of osteonecrosis in patients with SLE included isointense signal
      intensity relative to adjacent bone marrow, hypointense rim, marginal enhancement
      and unusual involvement of flat bones. Bilateral and multiple involvements were
      common.

PMID- 15246484
TI  - Primitive reflexes and postural reactions in the neurodevelopmental examination.
AB  - The primitive reflexes and the postural reactions comprise one of the earliest,
      simplest, and most frequently used tools among child neurologists to assess the
      central nervous system integrity of infants and young children. Infants with
      cerebral palsy have been known to manifest persistence or delay in the
      disappearance of primitive reflexes and pathologic or absent postural reactions.
      The clinical significance of asymmetric tonic neck reflex, Moro, palmar grasp,
      plantar grasp, Galant, Babinski, Rossolimo, crossed extensor, suprapubic
      extensor, and heel reflex, alone or in combination, as well as their contribution
      to the early diagnosis and differential diagnosis of cerebral palsy, have been
      demonstrated in a number of studies. Moreover, infants with 5 or more abnormal
      postural reactions have developed either cerebral palsy or developmental
      retardation as reported in a number of studies. Although a comprehensive
      neurologic examination in the context of a motor assessment instrument is
      preferable to an informal list of items, the combined examination of primitive
      reflexes and postural reactions should be considered by the child neurologist, as
      a simple but predictive screening test for the early identification of infants at
      risk for cerebral palsy. It is quick and easy to perform, both in nonhospital
      environments and in underdeveloped countries, where time and specific recourses
      are limited. The combined examination is also useful in developed countries
      because many developmental disorders such as cerebral palsy appear in nonrisk
      groups whereas others are not detected by metabolic screening programs.

PMID- 15246485
TI  - Visual functional magnetic resonance imaging in patients with Sturge-Weber
      syndrome.
AB  - The purpose of this study is to report different patterns of visual cortex
      activation in patients with Sturge-Weber syndrome as compared with healthy
      control subjects. Utilizing a visual paradigm of flashing lights, three children
      with Sturge-Weber syndrome were studied with functional magnetic resonance
      imaging. The results are compared with those documented in eight normal sedated
      children, and six young adult awake volunteers, using the same paradigms. All
      adult volunteers manifested bilateral activation in primary visual cortex
      (Brodmann's 17 and 18 areas). Two of them also had activation in secondary visual
      cortex (Brodmann's 19 area). In the eight sedated normal children, seven
      manifested activation in primary visual areas. The last exhibited no activation.
      The patients with Sturge-Weber syndrome demonstrated in the affected occipital
      lobe increased activation in one patient (11 months old), no activation in the
      second (12 years of age), and abnormal distribution of the activation in the
      third (11 months old). This report demonstrates that the vascular malformation of
      Sturge-Weber syndrome does not necessarily prevent cortical activation in the
      expected occipital cortex and may be associated with different patterns of
      abnormal activation. Assessing cortical function with functional magnetic
      resonance imaging in patients with Sturge-Weber syndrome may be helpful in
      decisions of surgical management and counseling.

PMID- 15246487
TI  - The use of bispectral index to monitor unconscious children.
AB  - The use of the Glasgow Coma Scale may be limited by the experience of physicians,
      errors resulting from subjectivity, the inability of patients to respond, and
      discontinuity. This study demonstrates that the Bispectral Index scores correlate
      well with scores from the Glasgow Coma Scale and that Bispectral Index scores can
      provide real-time, objective, and continuous monitoring of the consciousness
      level of critically ill children. Sixteen patients with consciousness
      disturbance, who were admitted to a pediatric intensive care unit of a tertiary
      university-affiliated children's hospital, were enrolled in this study. The
      patients received 34 Glasgow Coma Scale assessments and Bispectral Index scores.
      The age of patients ranged from 10 to 192 months (mean +/- S.E. = 68.4 +/- 12.3
      months). Glasgow Coma Scale ranged from 3 to 11 (mean +/- S.E. = 6.3 +/- 0.4),
      and Bispectral Index score ranged from 0 to 100 (mean +/- S.E. = 55.4 +/- 5.6). A
      positive correlation was found to exist between Glasgow Coma Scale and Bispectral
      Index score (r = 0.76, P < 0.001). In conclusion, the Bispectral Index score
      correlates well with the Glasgow Coma Scale in critically ill children who score
      between 3 and 11 on the Glasgow Coma Scale.

PMID- 15246486
TI  - Depression in parents of children with Duchenne muscular dystrophy.
AB  - This study examined depression, self-esteem, and mastery in the family caretakers
      of a group of males with Duchenne muscular dystrophy in comparison to a control
      group. A questionnaire based on the National Population Health Survey from
      Statistics Canada, a survey to collect information on the health of the Canadian
      population and related sociodemographic information, was conducted by telephone
      with 42 parents. The results were compared with the national data from the
      National Population Health Survey (1994 and 1999), matched for province of
      residence, number of children in the household, age, and marital status of the
      respondents. Parents of children with Duchenne muscular dystrophy had a higher
      probability of going through a major depressive episode and had significantly
      lower self-esteem and mastery scores than the national control group. None of the
      variables investigated (age, intelligence quotient, and ambulatory status of
      child or sex, age, and marital status of parent) could predict the depressive
      episode, with two exceptions. Parents without a partner had lower scores on the
      mastery scale, and parents of males older than 13 years of age were more likely
      to experience distress that interfered with life. It is incumbent on those caring
      for patients with Duchenne muscular dystrophy to counsel families regarding their
      potential to suffer a major depressive episode and to advise on appropriate
      therapy.

PMID- 15246488
TI  - Symptomatic occipital lobe epilepsy following neonatal hypoglycemia.
AB  - This study reports on the clinical, electrophysiologic, and neuroradiologic
      aspects of patients with epilepsy secondary to neonatal hypoglycemia. Fifteen
      patients with epilepsy and/or posterior cerebral lesions, and neonatal
      hypoglycemia were studied in the epilepsy clinic between February 1990 and March
      2003. The mean age was 12 years. The different types of neonatal hypoglycemia
      were as follows: four patients had transitional-adaptive, seven classic
      transient, two secondary-associated, and two severe recurrent hypoglycemia. As to
      epilepsy, we recognized a larger group of 12 patients characterized by focal
      seizures and posterior abnormalities on the electroencephalogram, the majority of
      whom had a good outcome, and a second group of two patients presenting
      electroclinical features of encephalopathy with refractory seizures. All patients
      except two manifested parieto-occipital lesions on neuroradiologic images.
      Neurologic examination was normal in one patient. Six patients had microcephaly;
      eight manifested visual disturbances. Fourteen patients were mentally retarded.
      One had a pervasive developmental disorder. This study indicates neonatal
      hypoglycemia may cause posterior cerebral lesions, abnormal findings at
      neurologic examination, and symptomatic epilepsy, most frequently occipital lobe
      epilepsy, usually with a good prognosis, and occasionally epileptic
      encephalopathy with refractory seizures. MRI studies are essential to define the
      characteristics of cerebral lesions after neonatal hypoglycemia.

PMID- 15246489
TI  - Sporadic major hyperekplexia in neonates and infants: clinical manifestations and
      outcome.
AB  - The aim of the present study is to report on the syndrome of sporadic major
      hyperekplexia during the neonatal period and early infancy, diagnosed in 39
      patients at an average age of 3.3 months, the most severely affected during the
      first month of life. The patients mainly presented with marked irritability and
      recurrent startles in response to handling or even minute sounds, accompanied by
      rhythmic jerky movements and occasionally breath-holding episodes. Family history
      was negative for hyperekplexia, although eight parents reported jerky leg
      movements during sleep. The hallmark of hyperekplexia consisted of a hyper-alert
      gaze and an exaggerated startle with delayed habituation, also elicited by nose
      tapping and air blowing on the face accompanied by increasing rigidity. Nine
      severely affected infants, presenting with relentless startles, marked stiffness,
      violent rhythmic jerks, and breath-holding episodes were treated with oral low
      doses of clonazepam and completely recovered. Overall, the debilitating symptoms
      of hyperekplexia gradually resolved in all 39 infants, and their developmental
      assessment by 2 years of age was within the normal range. Therefore a prompt
      diagnosis of hyperekplexia during the neonatal period and early infancy, and then
      treatment if required with benzodiazepines to alleviate the debilitating
      symptoms, may prevent life-threatening events and enable better feeding and
      handling. Establishing the diagnosis of such a relatively benign disorder with a
      favorable developmental outcome may avoid unjustified extensive investigations or
      unnecessary treatment, suspecting an ominous progressive neurologic disorder.

PMID- 15246490
TI  - Prognostic correlative values of the late-infancy MRI pattern in term infants
      with perinatal asphyxia.
AB  - The aim of this study was to define the risk ratios of the late-infancy magnetic
      resonance imaging pattern for long-term outcome in term infants with perinatal
      asphyxia. We evaluated 65 term infants with perinatal asphyxia and performed
      magnetic resonance imaging examinations between 4-12 months of age. Magnetic
      resonance imaging scans were classified as follows: (1) periventricular
      leukomalacia in 21 (32%) infants, (2) marked cortical atrophy in 17 (26%)
      infants, (3) multicystic encephalomalacia in 10 (15%) infants, (4) deep gray
      matter involvement in 8 (12%) infants, (5) focal cortical involvement in 6 (9%)
      infants, (6) myelination delay in 3 (5%) infants. The overall outcome was
      favorable in 19 (29%) of 65 infants. Infants with diffuse cortical involvement
      (multicystic encephalomalacia and marked cortical atrophy) are four times (odds
      ratio: 4.4 and 4.1 respectively) more likely to attain the unfavorable outcome
      than the infants with other patterns of magnetic resonance imaging. Infants with
      focal cortical involvement had relatively favorable outcome in 60% of the cases.
      In conclusion, it appears that the overall outcome of infants with perinatal
      asphyxia correlated well with the magnetic resonance imaging patterns obtained
      between 4 and 12 months of age.

PMID- 15246491
TI  - Clinical characteristics of Japanese children with optic neuritis.
AB  - The clinical characteristics of children with optic neuritis have been reported
      to be different from that of adults and to vary among different races. To
      determine the clinical characteristics of Japanese children with optic neuritis,
      we examined the medical records of 41 children who were diagnosed with optic
      neuritis at the Department of Ophthalmology of Chiba University Hospital between
      January 1979 and December 2001. Information on the sex, age of onset, laterality,
      initial visual acuity, final visual acuity, recent infections and immunizations,
      and presence of systemic neurologic diseases, such as multiple sclerosis or acute
      disseminated encephalomyelitis, was obtained. These findings revealed that the
      clinical features of optic neuritis in children were similar to those reported
      earlier. The percentage of optic neuritis cases that developed multiple sclerosis
      in children was similar to that for children in Europe and North America, and
      this percentage was not lower than that in adults in our clinic. These findings
      can be taken as the characteristics of optic neuritis of children in Japan.

PMID- 15246492
TI  - Subacute sclerosing panencephalitis in children: prevalence in South China.
AB  - This investigation reports the prevalence and clinical profile of subacute
      sclerosing panencephalitis in two developed cities of southern China. A territory
      wide survey was conducted to identify all subacute sclerosing panencephalitis
      cases diagnosed during 1988-2002 in Hong Kong and Macau. Altogether, 10 cases
      (male:female = 7:3) were identified of whom six were still alive. The prevalence
      rate of subacute sclerosing panencephalitis in Hong Kong and Macau in 2002 was 1
      per million total population or 5.5 per million children. The mean age of
      presentation was 9.4 years (range = 4-14 years). Presenting features included
      myoclonus (60%), deterioration in school performance (30%), and transient visual
      impairment (10%). The clinical course was highly variable. Most had subacute
      course, but two deteriorated rapidly and died within 6 months. Seven children had
      measles infection, and the majority of infection (86%) occurred during the world
      measles epidemic in 1988. The mean interval between measles infection and onset
      of subacute sclerosing panencephalitis was 6.5 years (range = 3-11 years). There
      has been an increasing trend of subacute sclerosing panencephalitis in southern
      China after the measles outbreak in 1988. Active surveillance of subacute
      sclerosing panencephalitis for those with measles infection during the 1988
      outbreak is necessary to conduct multicenter drug trials for this devastating
      disease.

PMID- 15246493
TI  - Clinical predictors for outcome in infants with epilepsy.
AB  - In this prospective study, the clinical parameters predictive for the outcome in
      infants with onset of epilepsy below 12 months of age (n = 60) were determined.
      At the end of the follow-up period, patients were included in a symptomatic or
      idiopathic group. In approximately 60% of all children, epilepsy could be
      controlled with standard antiepileptic monotherapy. The epilepsy was more
      difficult to control in the symptomatic group, reflected by the larger number of
      drug switches during follow-up. Seizure outcome was not influenced by age of
      onset, type of seizures, or electroencephalographic abnormalities at the epilepsy
      onset. Developmental outcome was significantly worse in the symptomatic group. In
      the idiopathic group, the control of epilepsy was the major developmental outcome
      factor, indicating a possible deleterious effect of seizures on brain development
      in that group.

PMID- 15246494
TI  - Influenza A-associated stroke in a 4-year-old male.
AB  - This case describes an ischemic stroke in a 4-year-old male associated with acute
      influenza A infection during the December 2003 nationwide influenza epidemic in
      the United States. To our knowledge, this is the first report of an association
      between influenza A and stroke in children.

PMID- 15246495
TI  - Congenital ataxia and mental retardation in three brothers.
AB  - Nonprogressive congenital ataxia is a complex group of disorders caused by a
      variety of etiologic factors, both environmental and genetic. Hereditary forms
      represent a substantial part of congenital ataxias, which are difficult to
      classify because of their phenotypic and genetic polymorphism. Despite the
      advances in molecular genetics, for most nonprogressive congenital ataxia the
      etiology is still unknown. This report describes three sons of nonconsanguineous
      healthy parents, who manifested a syndrome characterized by nonprogressive
      ataxia, mental retardation, pyramidal signs, ocular and ocular motor anomalies,
      associated with severe hypoplasia of the cerebellar vermis and hemispheres on
      neuroimaging. All the patients have presented psychomotor developmental delay. As
      differential diagnosis, a comparison is made between the clinical features of
      these patients and the previously reported cases of nonprogressive congenital
      ataxia. This report represents a further example of the phenotypic and genetic
      heterogeneity of the syndromes with congenital ataxia.

PMID- 15246496
TI  - Central pontine myelinolysis central pontine myelinolysis manifesting with
      massive myoclonus.
AB  - Central pontine myelinolysis is a rare neurologic disorder defined by symmetric
      demyelination in the central base of the pons. It usually manifests with
      neurologic signs such as impaired consciousness, ataxia, spastic quadriparesis,
      pseudobulbar signs, and the locked-in syndrome which is related to a
      disconnection syndrome at the pontine level. We report a 17-month-old patient
      with kwashiorkor and hyponatremia who developed acute massive myoclonus. Magnetic
      resonance imaging revealed a central pontine lesion. Central pontine myelinolysis
      is rare in infants, with only a few cases reported in the literature so far. This
      report presents the first infantile case of central pontine myelinolysis
      manifesting with massive myoclonus.

PMID- 15246497
TI  - Subacute sclerosing panencephalitis: a case with fulminant course after ACTH.
AB  - We report a 24-month-old male who developed rapidly progressive subacute
      sclerosing panencephalitis 17 months after measles infection. This patient had a
      history of measles infection at the age of 7 months and manifested acute
      encephalitis 1 month later. Developmental delay observed after encephalitis began
      to improve after a few months. His control electroencephalogram was normal at the
      age of 14 months. He was admitted to the hospital with flexor spasms and sudden
      head drops at the age of 24 months. His electroencephalogram revealed slow waves
      in the posterior regions of the brain. Vigabatrin was begun; his seizures
      increased with vigabatrin, and adrenocorticotropic hormone was added to the
      therapy. After five doses of adrenocorticotropic hormone, his clinical findings
      deteriorated rapidly. His second electroencephalogram revealed periodic
      discharges synchronized with myoclonias. He was diagnosed as having subacute
      sclerosing panencephalitis on the basis of clinical and laboratory findings. He
      lapsed into a vegetative state within a week and died at the age of 25 months. We
      report this rapidly progressive case to emphasize the importance of recognition
      of subacute sclerosing panencephalitis before applying steroids in children with
      myoclonic seizures.

PMID- 15246498
TI  - Pediatric ingestion of lamotrigine.
AB  - A 3-year-old female presented to the emergency department after ingesting forty
      six 25-mg tablets of lamotrigine that resulted in sedation, rash, and transient
      elevation of liver function tests. Her initial physical examination was
      significant for marked somnolence and a lacy reticular blanching rash. Laboratory
      studies were all within normal limits except for mildly elevated liver function
      tests. Initial plasma lamotrigine level was found to be elevated above adult
      therapeutic levels (25.3 microg/mL). Treatment consisted of gastric lavage
      followed by activated charcoal. The patient was subsequently observed in the
      pediatric intensive care unit where symptoms and laboratory abnormalities
      promptly resolved, and she was discharged 24 hours later without further
      complication. This case report describes the largest single ingestion of
      lamotrigine ever reported in a pediatric patient. The patient exhibited
      significant somnolence, rash, and liver function test abnormalities with only a
      slight elevation of serum level of lamotrigine above adult therapeutic levels.
      More research is required to investigate the toxic profile of lamotrigine in
      pediatric patients.

PMID- 15246499
TI  - Hair analysis differentiates chronic from acute carbamazepine intoxication.
AB  - This is a report of a 12-year-old epileptic child undergoing chronic treatment
      with carbamazepine who was found comatose. He was considered to have acute severe
      drug toxicity. Measurement of carbamazepine concentration in the patient's hair
      segments together with the carbamazepine blood levels were both important in
      determining the chronic nature of the patient's intoxication.

PMID- 15246500
TI  - Oral dyskinesia induced by fluoxetine therapy for infantile autism.

PMID- 15246501
TI  - Nucleated red blood cell counts.

PMID- 15246503
TI  - Lack of correlation between phenotypic techniques and PCR-based genotypic methods
      for identification of Enterococcus spp.
AB  - A total of 123 genetically-unrelated strains of Enterococcus spp. strains (51
      Enterococcus faecalis, 57 Enterococcus faecium, 10 Enterococcus gallinarum, and 5
      Enterococcus casseliflavus) were phenotypically identified by biochemical
      profiles and by using an automated method. The strains were also analyzed by a
      PCR assay to assess the accuracy of the phenotypically-based methods for
      identification of Enterococcus spp. With this aim, a PCR assay using different
      cell targets, which allows simultaneous detection of glycopeptide-resistant
      genotypes as well as identification to the species level by means of different
      gene targets, was used as the gold standard method. All 51 strains of E. faecalis
      were correctly identified, whereas 48 of 57 strains (84.2%) of E. faecium, were
      correctly identified. All of the strains of E. gallinarum and 3 out of 5 strains
      of E. casseliflavus were also correctly identified. The overall results showed
      that it is possible to identify Enterococcus spp. at the molecular level in less
      than 30 hours, compared with the 48-96 hours required for the phenotypically
      based methods. The excellent accuracy of the PCR assay in identifying these
      species, particularly E. faecium, must also be emphasized. These findings may
      have implications for the routine clinical identification of enterococci species.

PMID- 15246504
TI  - Prevalence of genes encoding for members of the staphylococcal leukotoxin family
      among clinical isolates of Staphylococcus aureus.
AB  - Well-characterized Staphylococcus aureus nasal and blood isolates (N = 429) were
      tested by polymerase chain reaction for the prevalence of genes that encode
      leukocidal toxins. The leukotoxin genes lukE+lukD were found at high prevalence,
      significantly more so in blood (82%) than in nasal isolates (60.5%). Although
      almost all isolates were positive for the gamma-hemolysin gene, none was positive
      for lukM. Genes encoding Panton-Valentine leukocidin (PVL) components were very
      rare in either nasal or blood isolates. The lukE+lukD-negative isolates were
      significantly more likely to be positive for the staphylococcal enterotoxin gene
      combination seg/sei (89.5%) and the toxic shock syndrome toxin-1 gene (39.3%)
      than lukE+lukD-positive isolates (41.7% and 12.7%, respectively). The lukE+lukD
      negative isolates were also more likely to show positivity for the accessory gene
      regulatory locus agr III, but less likely to be positive for the agr II locus.
      The co-possession of different virulence factors and their probable synergy
      should receive more attention in order to better understand their role in
      pathogenicity.

PMID- 15246505
TI  - Identification of Bacillus anthracis by multiprobe microarray hybridization.
AB  - We have developed a rapid assay based on microarray analysis of amplified genetic
      markers for reliable identification of Bacillus anthracis and its discrimination
      from other closely related bacterial species of the Bacillus cereus group. By
      combining polymerase chain reaction (PCR) amplification of six B. anthracis
      specific genes (plasmid-associated genes encoding virulence factors (cyaA, pagA,
      lef, and capA, capB, capC) and one chromosomal marker BA-5449) with analysis of
      amplicons by microarray hybridization, we were able to unambiguously identify and
      discriminate B. anthracis among other closely related species. Bacillus
      identification relied on hybridization with multiple individual microarray
      oligonucleotide probes (oligoprobes) specific to each target B. anthracis gene.
      Evaluation of the assay was conducted using several B. anthracis strains (with or
      without pXO1 and pXO2 plasmids) as well as over 50 other species phylogenetically
      related to B. anthracis, including B. cereus, B. thuringiensis, B. mycoides, and
      B. subtilis. The developed microarray analysis of amplified genetic markers
      protocol provides an efficient method for (i) unambiguous identification and
      discrimination of B. anthracis from other Bacillus species and (ii)
      distinguishing between plasmid-containing and plasmid-free Bacillus anthracis
      strains.

PMID- 15246506
TI  - Evaluation of the ELVIS plate method for the detection and typing of herpes
      simplex virus in clinical specimens.
AB  - This study was conducted to assess the reliability of a commercial enzyme-linked
      viral inducible system (ELVIS) (Diagnostic Hybrids, Inc., Athens, OH) for rapid
      detection and typing of herpes simplex virus (HSV). Results using ELVIS were
      compared to those of shell vial culture (SVC) and HSV detection with monoclonal
      antibodies and an immunoperoxidase stain plus typing with MicroTrak direct
      fluorescent antibodies (Trinity Biotech PLC, Wicklow, Ireland). Specimens
      yielding discrepant HSV results were tested by polymerase chain reaction (PCR);
      those with discrepant typing results were stained with Simulfluor (Chemicon,
      Temecula, CA). Of the 206 samples tested, 144 were negative and 54 were HSV
      positive by both methods (agreement, 96.1%). Five specimens were positive by
      ELVIS but negative by SVC; 3 of these were positive and 2 were negative by HSV
      PCR. Both of the latter were the result of mechanical problems early in the
      study. Three specimens were positive by SVC but negative by ELVIS; all 3 were
      positive by HSV PCR. After resolution of discrepancies, the sensitivity and
      specificity for detection of HSV were 95.0% and 100% for SVC, respectively, and
      95.0% and 98.6% for ELVIS. Of the 46 HSV-positive samples that were typed, 26
      were called type 2 and 18 were type 1 by both methods (agreement, 95.7%). The 2
      specimens with discrepant results were called HSV-2 by SVC, staining with
      MicroTrak, and HSV-1 with ELVIS; both of these were type 2 when stained with the
      Simulfluor reagent. ELVIS is a reliable alternative to SVC for rapid detection
      and typing of HSV.

PMID- 15246507
TI  - Evaluation of microplate Alamar blue assay for drug susceptibility testing of
      Mycobacterium avium complex isolates.
AB  - Fifty-one clinical isolates and 5 clarithromycin-resistant mutants of
      Mycobacterium avium complex (MAC) were tested for their susceptibility to
      clarithromycin by microplate Alamar blue assay (MABA). The susceptibility results
      were compared with the results obtained by the BACTEC 460 method. All clinical
      isolates were susceptible, while all mutants were resistant to clarithromycin by
      BACTEC. Eighty-six percent of the clinical isolates were susceptible by MABA, and
      one of the resistant mutants was misclassified as susceptible by this method. The
      overall agreement between MABA and BACTEC was 86%, indicating the usefulness of
      MABA in drug susceptibility testing of MAC.

PMID- 15246508
TI  - Differential diagnosis of Taenia saginata and Taenia saginata asiatica taeniasis
      through PCR.
AB  - New multiplex-PCR and PCR-linked restriction fragment length polymorphism
      protocols, derived from Taenia saginata HDP2 DNA sequence, have been designed
      that allow the simultaneous and specific identification of T. saginata and Taenia
      saginata asiatica. Proglottids expelled from 20 different Spanish taeniasis
      patients, previously diagnosed as T. saginata by both morphological
      identification and multiplex HDP2-PCR, were also examined by the newly developed
      PCR protocols, and the original diagnosis of T. saginata infection was confirmed.
      All of the 20 T. saginata samples were negative in the T. saginata asiatica
      specific PCR. Three authentic T. saginata asiatica samples were unambiguously
      identified as such in the T. saginata asiatica PCR. These new protocols have
      immediate potential for the specific, sensitive, and rapid identification of T.
      saginata asiatica and may assist in taxonomic studies.

PMID- 15246509
TI  - Morphotypic and genotypic characterization of sequential Candida parapsilosis
      isolates from an outbreak in a pediatric intensive care unit.
AB  - Candidemia outbreaks that due to cross-infection are an emerging problem in
      hospitals. Typing of microorganisms is an essential tool for understanding the
      epidemiologic aspects of the infection. Techniques based on phenotypic
      characteristics are inexpensive and easy to perform but are limited by their lack
      of reproducibility. This study assessed the value of several phenotypic and
      genotypic techniques that are used in epidemiologic investigations of Candida
      parapsilosis in clinical practice and used a combination of these methods to
      analyze outbreak of C. parapsilosis candidemia. Random amplification of
      polymorphic DNA polymerase chain reaction with several primers was unsatisfactory
      because it lacked discriminatory power. By simplifying the reading of the
      morphotypes, we increased their reproducibility for each malt agar and 2,3,5
      triphenyltetrazolium media (97% and 90%) and thus their suitability for its use.
      The combination of electrophoretic karyotype and the simplified morphotypes was
      rapid and practical to characterize the different clusters involved in the
      intensive care unit outbreak.

PMID- 15246510
TI  - In vitro activity and killing effect of the synthetic hybrid cecropin A-melittin
      peptide CA(1-7)M(2-9)NH(2) on methicillin-resistant nosocomial isolates of
      Staphylococcus aureus and interactions with clinically used antibiotics.
AB  - The in vitro activity of CA(1-7)M(2-9)NH(2), a 15-residue synthetic hybrid
      peptide derived from the sequences of cecropin A and melittin, alone and in
      combination with amoxicillin-clavulanate, imipenem, clarithromycin,
      ciprofloxacin, rifampin, and vancomycin, was investigated against 40 nosocomial
      isolates of methicillin-resistant Staphylococcus aureus. Antimicrobial activity
      of CA(1-7)M(2-9)NH(2) was measured by minimal inhibitory concentration, MBC, and
      time-kill studies. All isolates were inhibited at concentrations of 1 to 16
      microg/mL. Combination studies performed with S. aureusATCC 43300 demonstrated
      synergy only when CA(1-7)M(2-9)NH(2) was combined with amoxicillin-clavulanate
      and imipenem. Our findings show that CA(1-7)M(2-9)NH(2) is active against
      methicillin-resistant S. aureusand that its activity is enhanced when it is
      combined with several antimicrobial agents.

PMID- 15246511
TI  - In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical
      isolates associated with community-acquired respiratory tract and gram-positive
      cutaneous infections.
AB  - Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has
      demonstrated activity against a variety of bacterial pathogens, including
      resistant isolates, during preclinical studies. In vitro activities of
      tigecycline and comparators were tested against 11,859 recent (2000 and 2002)
      bacterial strains recovered from patients in 29 countries with community-acquired
      respiratory tract disease (3,317 gram-positive and -negative strains) and skin
      and soft tissue infections (8,542 gram-positive strains). All oxacillin
      susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline
      MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains;
      MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus
      pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group
      streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin
      susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5
      microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25
      microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220
      strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25
      microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12
      microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency
      of tetracycline and doxycycline markedly dropped in various resistant organism
      subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL.
      These findings confirm that tigecycline maintains a truly broad spectrum like the
      tetracycline class while enhancing potency. It also incorporates stability to the
      commonly occurring tetracycline resistance mechanisms, making it an attractive
      candidate for continued clinical development against pathogens causing serious
      community-acquired respiratory tract infections, as well as cutaneous infections.

PMID- 15246512
TI  - Determination of epidemic clonality among multidrug-resistant strains of
      Acinetobacter spp. and Pseudomonas aeruginosa in the MYSTIC Programme (USA, 1999
      2003).
AB  - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC)
      Programme was initiated in 1997 (1999 for the United States). This program
      monitors resistance in participant medical centers where carbapenems are
      prescribed and drug use data can be obtained. An earlier report found
      antimicrobial use was not a clear cause of local or aggregate changes in
      resistance rates. This study addresses the role of dissemination of resistant
      clones on susceptibility rates for nonfermentors, Acinetobacter spp. (ACB) and
      Pseudomonas aeruginosa (PSA). Carbapenem (CARB)-multidrug-resistant strains (MDR)
      from among 236 ACB and 1,111 PSA were tested by reference broth microdilution
      methods, automated ribotyping, and pulsed field gel electrophoresis to determine
      possible clonal dissemination. Each strain was also tested for metallo-beta
      lactamases (MbetaL) (phenotypic and polymerase chain reaction); and then analyzed
      by CARB-R rate and defined daily dose (DDD)/100 days use groupings (high,
      moderate, and low). For the aggregate 15 sites in the MYSTIC Programme each year,
      the CARB-resistant rate decreased over 5 years; but other drug-resistance rates
      generally escalated. Changes were not related to antimicrobial use calculations.
      The discovered clonally spread MDR-PSA strains were more frequent in high- (1.8
      clones/site) and moderate-resistance (0.6 clones/site) rate centers (21.7% to
      29.5% were clonal), compared with unique strains in low-resistance hospitals. ACB
      clonality was extreme in one geographic area, with dissemination of 5 different
      clones (931.7/B, C, or D; 1090.2/A; 167.5/A) in 4 centers (02, 04, 06, and 18).
      Resistance rates in ACB and PSA were clearly related to clonal occurrence and
      spread, and one MbetaL (VIM-7) was detected. Decreased CARB resistance rates from
      1999 through 2002 were directly attributed to the disappearance of resistance
      clones in some locations. In conclusion, ACB and PSA CARB and MDR resistance
      rates in MYSTIC Programme institutions have been greatly influenced by clonal
      dissemination and less by antimicrobial use patterns. The most serious examples
      of resistance were the clonality observed among ACB in New York City and the
      documented endemic nature of VIM-7-producing PSA (0.09% of all PSA isolates).
      Meropenem remained the most active antimicrobial agent tested in the program, and
      surveillance networks must implement epidemiologic typing to accurately assess
      the role of clonal spread on the study results.

PMID- 15246513
TI  - Prevalence and characterization of extended-spectrum beta-lactamases in
      Klebsiella pneumoniae and Escherichia coli isolates from Colombian hospitals.
AB  - Gram-negative pathogens harboring extended-spectrum beta-lactamases (ESBL) are
      widely prevalent in Latin America, but little is known about their prevalence in
      Colombia. A network of 8 tertiary care hospitals in Bogota, Medellin, and Cali,
      Colombia, was formed in January 2002 to determine the prevalence of ESBL
      producing Klebsiella pneumoniae and Escherichia coli. We characterized and
      established the molecular epidemiology of ESBLs from these hospitals. Data from
      1074 E. coli and 394 K. pneumoniae isolates were obtained from hospital
      laboratories during 6 months. Isolates resistant to third-generation
      cephalosporins or aztreonam were sent to a central laboratory. The prevalence of
      strains with this phenotype was 32.6% in K. pneumoniae and 11.8% in E. coli from
      the intensive care units, with slightly lower percentages from wards. Although
      TEM and SHV enzymes were present, the dominant class was CTX-M. Molecular typing
      of chromosomal DNA showed that most strains were not clonal.

PMID- 15246514
TI  - Clindamycin-resistant Streptococcus pyogenes: report of a case.
AB  - A sentinel isolate of clindamycin-resistant Streptococcus pyogenes from a case of
      mixed aerobic-anaerobic necrotizing fasciitis prompted our clinical laboratory to
      change its protocol and subsequently perform routine susceptibility testing on
      all S. pyogenes isolated from blood and soft tissue specimens. Emerging
      clindamycin resistance may have serious implications in the treatment of severe
      S. pyogenes infections.

PMID- 15246516
TI  - Radiology of bacterial pneumonia.
AB  - Bacterial pneumonia is commonly encountered in clinical practice. Radiology plays
      a prominent role in the evaluation of pneumonia. Chest radiography is the most
      commonly used imaging tool in pneumonias due to its availability and excellent
      cost benefit ratio. CT should be used in unresolved cases or when complications
      of pneumonia are suspected. The main applications of radiology in pneumonia are
      oriented to detection, characterisation and follow-up, especially regarding
      complications. The classical classification of pneumonias into lobar and
      bronchial pneumonia has been abandoned for a more clinical classification. Thus,
      bacterial pneumonias are typified into three main groups: Community acquired
      pneumonia (CAD), Aspiration pneumonia and Nosocomial pneumonia (NP).The usual
      pattern of CAD is that of the previously called lobar pneumonia; an air-space
      consolidation limited to one lobe or segment. Nevertheless, the radiographic
      patterns of CAD may be variable and are often related to the causative agent.
      Aspiration pneumonia generally involves the lower lobes with bilateral
      multicentric opacities. Nosocomial Pneumonia (NP) occurs in hospitalised
      patients. The importance of NP is related to its high mortality and, thus, the
      need to obtain a prompt diagnosis. The role of imaging in NP is limited but
      decisive. The most valuable information is when the chest radiographs are
      negative and rule out pneumonia. The radiographic patterns of NP are very
      variable, most commonly showing diffuse multifocal involvement and pleural
      effusion. Imaging plays also an important role in the detection and evaluation of
      complications of bacterial pneumonias. In many of these cases, especially in
      hospitalised patients, chest CT must be obtained in order to better depict these
      associate findings.

PMID- 15246517
TI  - Radiologic approach to the diagnosis of infectious pulmonary diseases in patients
      infected with the human immunodeficiency virus.
AB  - Nearly all patients infected with HIV experience respiratory infection at some
      point in the course of their illness. The spectrum of infections is varied and in
      order to generate a useful differential diagnosis based on imaging findings it is
      imperative for the radiologist to be aware of changing trends in disease
      prevalence and epidemiology, and the possible pathology related to new therapies.
      The characterization of the radiographic pattern in correlation with clinical
      findings and laboratory values (in particular the degree of immunosuppression as
      reflected in the CD4 level) would be helpful in narrowing the differential
      diagnosis of infectious pulmonary disease in HIV-positive patients. The most
      common radiologic patterns considered include areas of ground-glass,
      consolidation, nodules, and lymphadenopathy. We also include airways diseases and
      cavitary/cystic lesions because their prevalence has increased over recent years,
      and we also mention the significance of a normal chest radiograph in the
      suspicion of a lung infection. In most cases, the clinical and radiographic
      findings are sufficient for confident diagnosis. The radiologic diagnosis of
      thoracic infections in patients with AIDS has improved with the use of CT. The
      greatest value of CT is in excluding lung disease when the radiographic findings
      are equivocal and in confirming the presence of clinically suspected disease when
      the radiograph is normal.

PMID- 15246518
TI  - Imaging of opportunistic fungal infections in immunocompromised patient.
AB  - Opportunistic fungal infection is a common cause of serious morbidity and
      mortality in the immunocompromised host. Combination of pattern recognition with
      knowledge of the clinical setting is the best approach to pulmonary infectious
      processes. The aim of this article is to assess the chest radiographs and CT
      imaging features of different opportunistic fungal infections in
      immunocompromised patients.

PMID- 15246519
TI  - Radiological manifestations of pulmonary tuberculosis.
AB  - Pulmonary tuberculosis (TB) is a common worldwide lung infection. The
      radiological features show considerable variation, but in most cases they are
      characteristic enough to suggest the diagnosis. Classically, tuberculosis is
      divided into primary, common in childhood, and postprimary, usually presenting in
      adults. The most characteristic radiological feature in primary tuberculosis is
      lymphadenopathy. On enhanced CT, hilar and mediastinal nodes with a central
      hypodense area suggest the diagnosis. Cavitation is the hallmark of postprimary
      tuberculosis and appears in around half of patients. Patchy, poorly defined
      consolidation in the apical and posterior segments of the upper lobes, and in the
      superior segment of the lower lobe is also commonly observed. Several
      complications are associated with tuberculous infection, such as hematogenous
      dissemination (miliary tuberculosis) or extension to the pleura, resulting in
      pleural effusion. Late complications of tuberculosis comprise a heterogeneous
      group of processes including tuberculoma, bronchial stenosis bronchiectasis,
      broncholithiasis, aspergilloma, bronchoesophageal fistula and fibrosing
      mediastinitis. Radiology provides essential information for the management and
      follow up of these patients and is extremely valuable for monitoring
      complications.

PMID- 15246520
TI  - Demonstrating the effect of theophylline treatment on diaphragmatic movement in
      chronic obstructive pulmonary disease patients by MR-fluoroscopy.
AB  - INTRODUCTION: The purpose of this study was to determine the increase in
      diaphragmatic excursion of patients with chronic obstructive pulmonary disease
      (COPD) treated with theophylline by MR-fluoroscopy which is an innovative method
      to demonstrate effectiveness of this treatment. MATERIALS AND METHODS:
      Investigations were performed on a 0.3 T open MR unit. MR-fluoroscopy images of
      30 patients with COPD were obtained before and after theophylline treatment.
      Diaphragmatic movement values were recorded for evaluation. RESULTS: The response
      of the diaphragmatic movement in COPD patients treated with theophylline was
      evaluated by MR-fluoroscopy and an increase of 48% in diaphragmatic contractility
      was determined after the treatment. The increase in contractility was found to be
      parallel with respiratory function tests and clinical status. CONCLUSION:
      Diaphragmatic movement and response to the medical therapy in patients with COPD
      can be evaluated by MR-fluoroscopy method which can allow accurate measurements.

PMID- 15246521
TI  - Endobronchial metastasis from renal cell carcinoma: CT findings in four patients.
AB  - PURPOSE: To describe the CT findings of an endobronchial metastasis from a renal
      cell carcinoma (RCC). MATERIALS AND METHODS: The CT findings and clinical
      features of a histologically proven endobronchial metastasis from a RCC in four
      patients (three male, one female; age range, 64-80 years; mean age, 69 years)
      were reviewed retrospectively. The location of the metastasis in the airway,
      shape, the degree of tumor enhancement, and the associated pulmonary parenchymal
      abnormalities were analyzed. RESULTS: The histological subtype of the
      endobronchial metastases from the RCC was conventional in all cases. The tumors
      were located at the lobar (n = 1), both the lobar and segmental (n = 2), or the
      segmental (n = 1) bronchus. On the CT scan, the tumors were polypoid (n = 1), had
      a glove-finger appearance (n = 2), and exhibited branching in the airways and
      bronchial wall thickening (n = 1). The endobronchial metastasis from the RCC
      showed very high attenuation (84-128 HU), and strong enhancement (51.6-93.3 HU)
      on the contrast-enhanced CT images. The lung parenchymal lesions that had
      reticular opacities and ground glass opacities (n = 3). CONCLUSIONS: An
      endobronchial metastasis from a RCC appears as a strong-enhancing mass or
      bronchial wall thickening, accompanied by reticular opacities and ground glass
      opacities.

PMID- 15246522
TI  - Transthoracic CT-guided biopsy with multiplanar reconstruction image improves
      diagnostic accuracy of solitary pulmonary nodules.
AB  - OBJECTIVE: To evaluate the utility of multiplanar reconstruction (MPR) image for
      CT-guided biopsy and determine factors of influencing diagnostic accuracy and the
      pneumothorax rate. MATERIALS AND METHODS: 390 patients with 396 pulmonary nodules
      underwent transthoracic CT-guided aspiration biopsy (TNAB) and transthoracic CT
      guided cutting needle core biopsy (TCNB) as follows: 250 solitary pulmonary
      nodules (SPNs) underwent conventional CT-guided biopsy (conventional method), 81
      underwent CT-fluoroscopic biopsy (CT-fluoroscopic method) and 65 underwent
      conventional CT-guided biopsy in combination with MPR image (MPR method). Success
      rate, overall diagnostic accuracy, pneumothorax rate and total procedure time
      were compared in each method. Factors affecting diagnostic accuracy and
      pneumothorax rate of CT-guided biopsy were statistically evaluated. RESULTS:
      Success rates (TNAB: 100.0%, TCNB: 100.0%) and overall diagnostic accuracies
      (TNAB: 96.9%, TCNB: 97.0%) of MPR were significantly higher than those using the
      conventional method (TNAB: 87.6 and 82.4%, TCNB: 86.3 and 81.3%) (P < 0.05).
      Diagnostic accuracy were influenced by biopsy method, lesion size, and needle
      path length (P < 0.05). Pneumothorax rate was influenced by pathological
      diagnostic method, lesion size, number of punctures and FEV1.0% (P < 0.05).
      CONCLUSION: The use of MPR for CT-guided lung biopsy is useful for improving
      diagnostic accuracy with no significant increase in pneumothorax rate or total
      procedure time.

PMID- 15246523
TI  - Low-dose CT of the thorax in cancer follow-up.
AB  - PURPOSE: To evaluate the quality of low-dose computed tomography (CT) images in
      the follow-up of cancer patients. MATERIALS AND METHODS: We selected patients
      with urogenital (n = 7) or esophageal cancer (n = 13) who were attending routine
      follow-up between April and July 2001. After water and chest phantom studies to
      decide the scan parameters, postcontrast low-dose CT scans were obtained at 60 mA
      (45 mA s) with a smoothing kernel. Three radiologists reviewed the CT scans of
      the thorax independently for overall image quality and anatomic detail in both
      mediastinal and lung windows. They subjectively rated the images on a four-point
      scale (0: poor, 1: fair, 2: good, 3: excellent) according to graininess and
      sharpness. RESULTS: The average score of the low-dose CT for the lung window was
      2.85, which was equivalent to control images. The average score for the
      mediastinal window was 1.77, which was lower than that of the control CT scan
      (2.62, P < 0.001) and almost identical to that of the chest phantom experiment.
      Nine of the 20 cases had abnormal findings; low-dose CT scans depicted them well
      and offered sufficient information for diagnosis. The radiation exposure was
      reduced by about half. CONCLUSION: The image quality of low-dose thoracic CT was
      satisfactory for both mediastinal and lung windows in the follow-up of cancer
      patients.

PMID- 15246524
TI  - Comparison of chest radiography and high-resolution computed tomography findings
      in early and low-grade coal worker's pneumoconiosis.
AB  - INTRODUCTION: High-resolution computed tomography (HRCT) is more sensitive than
      chest X-ray (CXR) in the depiction of parenchymal abnormalities. We aimed to
      present and compare CXR and HRCT findings in coal workers with and without early
      and low-grade coal worker's pneumoconiosis (CWP). MATERIALS AND METHODS: 71 coal
      workers were enrolled in this study. All workers were male. The CXR and HRCT of
      those workers were obtained and graded by two trained readers. HRCT's were graded
      according to Hosoda and Shida's Japanese classification. After grading, 67
      workers with CXR profusion 0/0-2/2 were included in the study. Four patients with
      major opacity were excluded. Profusion 0/1 to 1/1 cases were accepted as early
      and profusion 1/2 and 2/2 cases as low-grade pneumoconiosis. RESULTS: Discordance
      between CXR and HRCT was high. Discordance rate was found higher in the early
      pneumoconiosis cases with negative CXR than low-grade pneumoconiosis (60, 36 and
      8%, respectively). When coal miners with normal CXR were evaluated by HRCT, six
      out of 10 cases were diagnosed as positive. In low-grade pneumoconiosis group,
      the number of patients with positive CXR but negative HRCT were low in comparison
      to patients with CXR negative and early pneumoconiosis findings. Most of the CXR
      category 0 patients (10/16) were diagnosed as category 1 by HRCT. Eleven cases
      diagnosed as CXR category 1 were diagnosed as category 0 (7/11) and category 2
      (4/11) by HRCT. In CXR category 2 (eight cases), there were four cases diagnosed
      as category 1 by HRCT. CONCLUSIONS: Discordance between CXR and HRCT was high,
      especially for CXR negative and early pneumoconiosis cases. The role of CXR in
      screening coal workers to detect early pneumoconiosis findings should be
      questioned. We suggest using HRCT as a standard screening method instead of CXR
      to distinguish between normal and early pneumoconiosis.

PMID- 15246525
TI  - Endovascular treatment of abdominal aortic aneurysms--6 years of experience with
      Ella stent-graft system.
AB  - PURPOSE: Evaluation of 6-year results of abdominal aortic aneurysm (AAA)
      treatment by Ella stent-grafts with regard to safety and effectivity in relation
      to morphology of the aneurysm. METHODS: From a group of 172 patients with AAA, in
      whom elective endovascular treatment was considered, 120 of them (69.8%) were
      found to be suitable for this type of therapy. The bifurcated type of stent-graft
      was implanted in 97 patients, uniiliacal type in 19 patients and only four
      patients were found to be suitable for tubular type of stent-graft. Additional
      necessary procedures (internal iliac artery occlusion or contralateral common
      iliac artery occlusion in a group of patients with uniiliacal type of stent
      graft) were performed surgically during the stent-graft implantation. CT and US
      controls were performed at 3, 6 and 12 months after implantation, later every 12
      months. RESULTS: Primary technical success was achieved in 109 of the 120
      patients (91%). Primary endoleak was recorded in 11 patients (primary endoleak
      type Ia in seven patients, type Ib in three patients and type IIIa in one
      patient). Assisted technical success after reintervention or spontaneous seal was
      98.3%. Surgical conversion was indicated in two patients (1.7%). Perioperative
      mortality rate was 3.3%. Total average follow-up period was 20.7 months (range
      from 2 to 60 months). In nine patients (7.5%) secondary endoleak type II was
      found at control CT or US, in three patients partial thrombosis of the stent
      graft was found. There was no aneurysm rupture during follow-up. CONCLUSION:
      Treatment of AAA with Ella stent-graft system is effective and safe. Bifurcated
      stent-graft is the most frequently used type. Uniiliacal type of stent-graft is
      used by us only in cases of complicated morphology.

PMID- 15246526
TI  - The complete mitochondrial genome of the javeline goby Acanthogobius hasta
      (Perciformes, Gobiidae) and phylogenetic considerations.
AB  - We isolated Acanthogobius hasta mitochondrial DNA by long-polymerase chain
      reaction (long-PCR) with conserved primers, and sequenced this mitogenome with
      primer walking. The resultant A. hasta mitochondrial DNA sequence was found to
      consist of 16,663 bp with a structural organization conserved relative to that of
      other fish. In this paper, we report the basic characteristics of the A. hasta
      mitochondrial genome including structural organization, base composition of rRNAs
      and the tRNAs and protein-encoding genes, and characteristics of mitochondrial
      tRNAs. These findings are applicable to molecular phylogenetics in the suborder
      Gobioidei.

PMID- 15246527
TI  - Identification and biochemical characterization of an avian sulfatase homologous
      to the human ARSE, the gene for X-linked chondrodysplasia punctata.
AB  - Despite many efforts, the mouse homolog of ARSE, the gene implicated in X-linked
      recessive chondrodysplasia punctata, has not yet been identified. This absence
      has so far impaired a deep study of the role of this gene. For this reason, we
      searched the avian homolog and here report the identification of a chicken
      sulfatase, cARS, that shares high degree of homology with the cluster of
      sulfatases located on the short arm of the human X chromosome. cARS activity
      against a sulfated artificial substrate is heat labile and inhibited by warfarin,
      features that are characteristic of ARSE. The expression in pharyngeal arches,
      somites, and leg buds during chick development is consistent with cARS being the
      functional ortholog of ARSE, matching the tissues affected in this genetic
      disorder. The identification of the ARSE chicken gene is an important step for
      the study of its natural substrate and its role during development.

PMID- 15246528
TI  - Analysis of the compositional biases in Plasmodium falciparum genome and proteome
      using Arabidopsis thaliana as a reference.
AB  - Comparative genomic analysis of the malaria causative agent, Plasmodium
      falciparum, with other eukaryotes for which the complete genome is available,
      revealed that the genome from P. falciparum was more similar to the genome of a
      plant, Arabidopsis thaliana, than to other non-apicomplexan taxa. Plant-like
      sequences are thought to result from horizontal gene transfers after a secondary
      endosymbiosis involving an algal ancestor. The use of the A. thaliana genome and
      proteome as a reference gives an opportunity to refine our understanding of the
      extreme compositional bias in the P. falciparum genome that leads to a proteome
      wide amino acid bias. A set of pairs of non-redundant protein homologues was
      selected owing to rigorous genome-wide sequence comparison methods. The
      introduction of A. thaliana as a reference was a mean to weight the magnitude of
      the protein evolutionary divergence in P. falciparum. The correlation of the
      amino acid proportions with evolutionary time supports the hypothesis that amino
      acids encoded by GC-rich codons are directionally substituted into amino acids
      encoded by AT-rich codons in the P. falciparum proteome. The long-term deviation
      of codons in malarial sequences appears as a possible consequence of a genome
      wide tri-nucleotidic signature imprinting. Additionally, this study suggests
      possible working guidelines to improve the accuracy of P. falciparum sequence
      comparisons, for homology searches and phylogenetic studies.

PMID- 15246529
TI  - Global heterochromatic colocalization of transposable elements with
      minisatellites in the compact genome of the pufferfish Tetraodon nigroviridis.
AB  - Because of its unusual high degree of compaction and paucity of repetitive
      sequences, the genome of the smooth pufferfish Tetraodon nigroviridis is the
      subject of a well-advanced sequencing project. An astonishing diversity of
      transposable elements not found in the human and the mouse has been observed in
      the genome of T. nigroviridis. Due to the difficulty of assembling repeat-rich
      regions, the whole genome shotgun sequencing approach will probably fail to
      reveal the general organisation of this compact vertebrate genome. Therefore, in
      order to gain new insights into the global distribution pattern of repeated DNA
      in the genome of T. nigroviridis, we have reconstructed partial/complete
      repetitive sequences from data generated by the genome project and performed
      double-colour fluorescent in situ hybridization (FISH) analysis for
      representatives of three major categories of repeated sequences including two
      minisatellites (ms100 and ms104), two DNA transposons (Tol2 and Buffy1) and two
      non-long terminal repeat (LTR) retrotransposons (Rex3 and Babar). We show that
      DNA transposons and retroelements very frequently colocalize with minisatellites
      and mostly accumulate within heterochromatic regions. These results, which have
      not been reported so far for the fugu Takifugu rubripes, show that repeated
      elements are generally excluded from gene-rich regions in T. nigroviridis and
      underline the extreme degree of compartmentalization of this compact genome. The
      genome organization of the pufferfish is clearly different from that observed in
      humans, where repeated sequences make up an important fraction of euchromatic
      DNA, and is more similar to that observed in the fruit fly Drosophila
      melanogaster.

PMID- 15246530
TI  - Expansion and divergence of the GH locus between spider monkey and chimpanzee.
AB  - Growth hormone (GH) has been previously described as showing distinct
      evolutionary stories between primates and other mammals. A burst of changes and
      successive amplification events took place in the primate lineage giving rise to
      a multigene family in the three Anthropoidea lineages. Polymerase chain reaction
      (PCR) was used to obtain the genes and the intergenic regions comprising the GH
      loci of the spider monkey (Ateles geoffroyi), a New-World primate, and of the
      chimpanzee (Pan troglodytes), an ape. The intergenic sequences of both species
      were screened by hybridization to detect copies of the Alu family, which have
      been implicated in the formation of the human GH locus. The GH locus of the
      spider monkey contains at least six GH-related genes, four of them were cloned.
      Likewise, five short intergenic sequences of approximately 3 kb were amplified
      and cloned. On the other hand, in the chimpanzee four new placental lactogen (PL)
      genes as well as four intergenic regions were amplified. Consequently, in this
      ape, six genes (two GHs, previously obtained, and four PLs) are clustered,
      separated by intergenic sequences of different lengths (two short ones of about 5
      kb, and at least two long ones between 9 and 13 kb). The presence of Alu
      sequences within the intergenic regions of both GH loci corroborates the current
      hypothesis that they acted as a driving force for the locus expansion. GH
      sequence comparisons reveal that several gene-conversion events might have
      occurred during the formation of this genome region, which has undergone
      independent evolution in the three Anthropoidea branches. To establish the GH's
      evolutionary history may prove to be a difficult task due to these gene
      conversion events.

PMID- 15246531
TI  - Gene amplification and cold adaptation of pepsin in Antarctic fish. A possible
      strategy for food digestion at low temperature.
AB  - Cold-adapted organisms have developed a number of adjustments at the molecular
      level to maintain metabolic functions at low temperatures. Among other features,
      they can produce enzymes characterized by a high turnover number or a high
      catalytic efficiency. The present work is aimed at investigating the process of
      food digestion at low temperature through the study of pepsins in Antarctic
      notothenioids. For such a purpose, we have cloned and sequenced three forms of
      pepsin A and a single form of gastricsin from the gastric mucosa of Trematomus
      bernacchii (rock cod). Phylogenetic analysis has suggested that the three pepsin
      A isotypes arose from two gene duplication events leading to the most ancestral
      pepsin A3 and to the most recent forms represented by pepsin A1 and pepsin A2.
      Molecular modeling has unraveled significant structural differences in these
      enzymes with respect to their mesophilic counterparts. Hydropathy and flexibility
      determined on the substrate-binding subsites of Antarctic and mesophilic pepsins
      have shown for pepsin A2 reduced hydropathy and increased flexibility at the
      level of the substrate cleft, features typical of cold-adapted enzymes. Northern
      blot analysis of RNA from rock cod gastric mucosa hybridized with molecular
      probes designed on specific regions of different pepsin forms has shown that rock
      cod pepsin genes are expressed at comparable levels. The present results suggest
      that the Antarctic rock cod adopted two different strategies to accomplish
      efficient protein digestion at low temperature. One mechanism is the gene
      duplication that increases enzyme production to compensate for the reduced
      kinetic efficiency, the other is the expression of a new enzyme provided with
      features typical of cold-adapted enzymes.

PMID- 15246532
TI  - Characterization of multiple members of the HSP70 family in platyfish culture
      cells: molecular evolution of stress protein HSP70 in vertebrates.
AB  - A shift from 28 to 37 degrees C in the incubation temperature of a culture of the
      platyfish fibroblast cell line, EHS cells (platyfish fibroblast cell line),
      induced a set of stress proteins. A two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) analysis showed that the cells expressed three
      genetically distinct forms of heat-shock protein 70 (HSP70) family proteins: heat
      inducible forms of HSP70, the constitutively expressed heat-shock cognate protein
      70 (HSC70) and its phosphorylated isoform, and the glucose-regulated protein 78
      (GRP78). Three different clones encoding two major isoforms of heat-inducible
      HSP70, platyfish HSP70-1 and HSP70-2, and of the HSC70 were isolated from a
      platyfish cDNA library. We compared the deduced amino acid sequences of the
      platyfish HSP70 and HSC70 proteins with those of other vertebrates. Phylogenetic
      analysis showed that vertebrate HSP70 could be classified into four cluster
      groups: (a) fish HSP70, with two isoforms of heat-inducible HSP70 in fish, fish
      HSP70-1 and HSP70-2; (b) the mammalian testis-specific HSP70-related protein
      HST70; (c) the mammalian heat-inducible HSP70B'; and (d) the mammalian major
      histocompatibility complex (MHC)-linked HSP70, including the MHC-linked heat
      inducible HSP70 and the testis-specific HSP70-related protein. These findings
      suggest that vertebrate HSP70 was derived from a single ancestral HSP70 gene
      during vertebrate evolution and that multiple copies of heat-inducible HSP70 were
      probably evolved during genetic divergence in fish and higher vertebrates.

PMID- 15246533
TI  - Gene structure and molecular analysis of Arabidopsis thaliana ALWAYS EARLY
      homologs.
AB  - Drosophila always early (aly) is essential for spermatogenesis, and is related to
      the LIN-9 protein of Caenorhabditis elegans; lin-9 is a class B Synthetic
      Multivulva gene (synMuvB) required for gonadal sheath development. Aly/LIN-9 have
      two conserved regions, called domains 1 and 2, which have been identified in
      homologous proteins from several multicellular eukaryotes, including the model
      plant Arabidopsis thaliana. We cloned and sequenced cDNAs of three different A.
      thaliana ALWAYS EARLY homologs (AtALY1, AtALY2 and AtALY3), analysed the
      expression pattern of these three genes and show that AtALY1, like Aly, is
      nuclear localised. We also demonstrate that the plant homologs of aly/lin-9
      contain an additional N-terminal myb domain not present in the animal Aly/LIN-9
      proteins, and that part of the ALY/LIN-9 conserved domain 1 in the predicted
      plant proteins is related to the TUDOR domain.

PMID- 15246534
TI  - Complete nucleotide sequence and organization of the naphthalene catabolic
      plasmid pND6-1 from Pseudomonas sp. strain ND6.
AB  - Pseudomonas sp. strain ND6, which was isolated from industrial wastewater in
      Tianjin, China, was capable of dissimilating naphthalene as sole carbon and
      energy sources. We identified one plasmid, pND6-1, which was associated with the
      metabolism of naphthalene and determined the complete nucleotide sequence of pND6
      1 (101,858 bp) using a whole-genome-shotgun approach. Computational analyses
      indicated that the naphthalene metabolism of the strain ND6 is associated with
      this plasmid. This is the first report of a complete sequence of naphthalene
      catabolic plasmid. pND6-1 encodes 102 putative coding sequences (CDSs). Among
      them, 23 CDSs were predicted to be involved in naphthalene catabolism, 14 were
      predicted to be involved in transposition and integration, 2 encoded putative
      transporters, 3 were putative transcriptional regulators, and 9 were proteins
      necessary for plasmid replication and partitioning. Most of the naphthalene
      catabolic genes of pND6-1 have 99-100% identity in amino acid sequences
      homologous to their nearest counterparts found in plasmid pDTG1, NAH7 and in a
      chromosome region in Pseudomonas stutzeri AN10 except for two duplicated genes
      (ND013 and ND016). Results of this study indicated that globally distributed
      naphthalene catabolic genes are highly conserved among different bacterial
      species.

PMID- 15246535
TI  - Characterization of rat heme oxygenase-3 gene. Implication of processed
      pseudogenes derived from heme oxygenase-2 gene.
AB  - Heme oxygenase (HO) is an enzyme responsible for the physiological degradation of
      heme to produce iron, CO and biliverdin. The released iron is recycled and
      represents the major source of this metal in heme homeostasis. A putative role as
      messenger in a signaling pathway is suggested for CO. Biliverdin, together with
      bilirubin, may function as an antioxidant. Thus far, three isoforms of HO, HO-1,
      HO-2 and HO-3 have been described. While HO-1 and HO-2 have been extensively
      investigated, HO-3 is still an elusive and poorly understood isoform. In this
      study, we examined the structure of the rat HO-3 gene with genomic PCR. However,
      we failed to isolate the reported HO-3 gene but, instead, found two HO-3-related
      genes, tentatively named HO-3a and HO-3b, whose sequences differed slightly from
      each other. Neither gene had any introns and consisted only of exon 2 through 5
      of the HO-2 gene, though their sequences were not completely identical with that
      of HO-2. A stop codon was introduced within the coding regions of these genes due
      to frame-shift. The nucleotide sequence of their 5'-upstream region largely
      agreed with long interspersed nuclear element 3. No HO-3-related mRNAs were
      amplified by RT-PCR, and no HO-3-related proteins were detected in tissues by
      Western blot analysis. Our results suggested that there are no functional HO-3
      genes in rat and that the HO-3a and HO-3b genes are processed pseudogenes derived
      from HO-2 transcripts.

PMID- 15246536
TI  - PfADA2, a Plasmodium falciparum homologue of the transcriptional coactivator ADA2
      and its in vivo association with the histone acetyltransferase PfGCN5.
AB  - The transcriptional coactivator ADA2 is an evolutionarily conserved component of
      histone acetyltransferase (HAT) complexes involved in chromatin remodeling and
      transcriptional regulation in eukaryotes. The Plasmodium falciparum homologue,
      PfADA2, has a 7737 bp open reading frame, encoding a protein of 2578 amino acids
      with an ADA2-like domain located near the C-terminus. The annotated PfADA2 in the
      parasite genome is Pf10_143, located on chromosome 10. Sequence analysis
      demonstrated the presence of an ADA2 homologue in each Plasmodium species
      selected for genome sequencing. Mapping of the 5' transcriptional initiation
      sites suggested that PfADA2 transcription was initiated from multiple sites.
      Northern analysis detected a major transcript of approximately 8.5 kb in
      erythrocytic stage parasites. An antiserum raised against the internal ADA2-like
      domain detected multiple proteins from mixed blood stages, suggesting that PfADA2
      may be proteolytically processed. In comparison, affinity-purified anti-GCN5
      antibodies reacted with a major protein of approximately 200 kDa and
      immunoprecipitated proteins from the parasite lysate with HAT activity similar to
      that of the recombinant GCN5. Moreover, this GCN5-like HAT activity could also be
      precipitated with anti-PfADA2 antibodies, indicating that PfADA2 is associated
      with PfGCN5 in vivo. To illustrate whether PfADA2 could functionally replace the
      yADA2, complementation experiments were performed. However, the ADA2-like domain
      of PfADA2 failed to rescue the yeast ada2(-) mutant, probably due to significant
      divergence between the two genes. Taken together, these results indicate the
      presence of PfADA2-PfGCN5 complex(es) in the malaria parasite, which may have
      conserved functions in chromatin remodeling and gene regulation.

PMID- 15246537
TI  - Conserved amino acid sequences confer nuclear localization upon the Prophet of
      Pit-1 pituitary transcription factor protein.
AB  - Prophet of Pit-1 (PROP1) is a homeodomain transcription factor essential for
      development of the mammalian anterior pituitary gland. Studies of human patients
      and animal models with mutations in their Prop1 genes have established that PROP1
      is required for the correct development or sustained function of the hormone
      secreting cells that regulate physiological pathways controlling growth,
      reproduction, metabolism, and the stress response. By comparative analysis of
      mammalian Prop1 genes and their encoded proteins, including cloning the ovine
      Prop1 gene and its products, we demonstrate that two conserved basic regions (B1
      and B2) of the PROP1 protein located within the homeodomain are required for
      nuclear localization, DNA binding, and target gene activation. Interestingly,
      missense mutations in the human Prop1 gene causing amino acid changes in both the
      B1 and B2 regions have been associated with combined pituitary hormone deficiency
      (CPHD) diseases, suggesting that disruption of nuclear localization may be part
      of the molecular basis of such diseases. The ovine Prop1 gene has three exons and
      two introns, a different structure compared with that of the bovine gene. Two
      alleles of the ovine gene were found to encode protein products with different
      carboxyl terminal domain sequences. We demonstrate that the two alleles are
      distributed in different breeds of sheep. Finally, we show for the first time
      that the PROP1 protein is associated with the nuclear matrix.

PMID- 15246538
TI  - Identification of positive and negative regulatory regions controlling expression
      of the Xenopus laevis betaTrCP gene.
AB  - betaTrCP mediates the ubiquitination and subsequent degradation of several key
      molecules thereby playing a relevant role in different cellular processes during
      development and in the adult. In Xenopus embryo, betaTrCP acts as a negative
      regulator of Wnt signaling by interacting with beta-catenin. In this paper, we
      report results of the study on expression and regulation of the Xenopus betaTrCP
      gene. We found that xbetaTrCP is expressed in Xenopus oocytes as three
      transcripts, which very likely correspond to the previously identified localized
      mRNAs, and four isoforms. The xbetaTrCP promoter functional and structural
      analysis showed the presence of elements target of positive transcriptional
      control. Among them, we have identified a beta-catenin/Tcf signaling responsive
      region and a 45-bp element containing a sequence motif conforming to the SRF
      binding site, closer to the transcription initiation sites. There are also
      elements of transcriptional negative control.

PMID- 15246539
TI  - Opposite conditioned place preference responses to endomorphin-1 and endomorphin
      2 in the mouse.
AB  - An unbiased conditioned place preference paradigm was used to evaluate the reward
      effect of selective endogenous mu-opioid ligands, endomorphin-1 and endomorphin
      2, in male CD-1 mice. Pre- and post-conditioning free-movement were measured on
      day 1 and day 5, respectively. Conditioning sessions were conducted twice daily
      from day 2 through day 4 consisting of the alternate injection of conditioning
      drug or vehicle. Intracerebroventricular (i.c.v.) injection of endomorphin-1 (0.3
      10 microg) induced place preference in a dose-dependent manner; whereas,
      endomorphin-2 (1-10 microg) dose-dependently induced place aversion. Both
      endomorphin-1-induced place preference and endomorphin-2-induced place aversion
      were blocked by pretreatment i.c.v. with mu-opioid receptor antagonist, beta
      funaltrexamine. Selective delta-opioid receptor antagonist, naltrindole, co
      administered i.c.v. with endomorphin-1 or endomorphin-2 did not affect reward
      effect. However, endomorphin-2-induced place aversion, but not endomorphin-1
      induced place preference, was blocked by the i.c.v.-administered selective kappa
      opioid receptor antagonist, WIN 44,441-3. It is concluded that endomorphin-1
      produces conditioned place preference, which is mediated by the stimulation of mu
      , but not delta- or kappa-opioid receptors, while endomorphin-2 produces
      conditioned place aversion, which is mediated by the stimulation of mu- and kappa
      , but not delta-opioid receptors.

PMID- 15246540
TI  - The mechanism of inhibition by xanthine of adenosine A1-receptor responses in rat
      hippocampus.
AB  - We have recently observed that the free radical-generating mixture of xanthine
      and xanthine oxidase (X/XO) can suppress the inhibitory effects of adenosine on
      synaptic transmission in the hippocampus, but that this action can be mimicked by
      xanthine alone. We have now clarified the mechanism of these interactions by
      using the new, potent and highly selective inhibitor of xanthine oxidase, 1-(3
      cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700). Field excitatory
      postsynaptic potentials (fEPSPs) were recorded in the CA1 region of rat
      hippocampal slices. X/XO induced a long-lasting increase of fEPSP slope and
      significantly reduced the presynaptic inhibitory effect of adenosine. Both these
      actions were prevented by Y-700 at a concentration of only 200nM. Similarly the
      superfusion of xanthine alone increased fEPSP slope and reduced sensitivity to
      adenosine but these effects were also prevented by Y-700. The results indicate
      that the antagonism of adenosine responses by X/XO or by xanthine alone are
      entirely attributable to the activity of the added or endogenous XO activity,
      probably generating free radicals, and are not likely to be caused by a direct
      antagonistic action at the xanthine-sensitive site on the adenosine receptor.

PMID- 15246541
TI  - Switch of K+ buffering conditions in rabbit retinal Muller glial cells during
      postnatal development.
AB  - Although spatial buffering of excess extracellular K+ by K+ channels is a main
      function of retinal glial (Muller) cells, there are severe limitations to long
      distance K+-spatial buffering that have been predicted for (immature) glial
      cells: (i) a lack of inwardly rectifying K+ (Kir) channels [Glia 21(1997) 46];
      and (ii) high internal resistance of outgrowing (cable like) processes [W. Rall,
      Handbook of Physiology, Section 1, vol. 1, Part 1, American Physiological
      Society, Bethesda, 1977, pp. 39-97]. In order to determine if changes in
      developing Muller cells improve or worsen their capability of carrying K+ spatial
      buffering currents, we compared the whole-cell currents of acutely isolated
      Muller cells at 5, 11 and 28 postnatal days of rabbits. Both K+-spatial buffer
      limitations described above were found in early postnatal stage (5 days),
      however, the cells overcome these limitations shortly after 11 days. During the
      period of 11-28 days, rabbit Muller cells simultaneously increase stalk axial
      conductance and express Kir channels. Both processes take place during the
      critical stage of retinal maturation, and should dramatically improve "cable" K+
      spatial buffering.

PMID- 15246542
TI  - Strain dependence of receptor regulation on chemical preconditioning in mice
      hippocampus.
AB  - While one current focus for studying mechanisms of disease is investigation of
      transgenic mice confounding effects of the background strain often are neglected.
      We investigated mRNA expression of known markers of hypoxic tolerance by a
      semiquantitative RT-PCR (adenosine receptors (A1 and A3), nitric oxide synthases
      (eNOS and nNOS), APP production, progesterone receptor, and estrogen receptors
      alpha and beta) in CD-1, C3H, and B6 mice. We found differences in the baseline
      mRNA expression of adenosine A3 receptors in C3H mice and neuronal NOS in B6 mice
      as well as a distinct regulation of adenosine A3 receptors and estrogen receptor
      beta (no changes in C3H and B6 compared to upregulation in CD-1) on treatment of
      animals with a low dosage of 3-nitropropionate (20mg/kg body weight, i.p.). We
      conclude that the choice of background strain may confound interpretation of the
      effects of specific transgens in the study of the mechanisms of primary and
      induced hypoxic tolerance.

PMID- 15246543
TI  - Expression of natriuretic peptides in rat Muller cells.
AB  - Natriuretic peptides (NPs) have been shown to modulate neuronal activities. By
      immunohistochemistry and confocal microscopy, we examined expression of atrial NP
      (ANP), brain NP (BNP) and C-type NP (CNP) in rat retina. Our results showed that
      these peptides were differentially expressed in the neural retina. While strong
      ANP-, BNP- and CNP-immunoreactivity (IR) was clearly seen in the outer and inner
      plexiform layers and on numerous neurons in the inner nuclear layer, BNP- and CNP
      , but not ANP-IR, was present in some ganglion cells. Furthermore, ANP, BNP and
      CNP were expressed in Muller cells with distinct profiles, as shown by double
      labeling of NPs and vimentin. Labeling for BNP was rather strong in the main
      trunks, major processes, but hardly detectable in the endfeet. The expression
      profile for ANP was similar, but with a much lower level. On the contrary, the
      endfeet and major processes in the inner retina were strongly CNP-positive, with
      the main trunks and other major processes in the outer retina much less labeled.
      These results raise a possibility that NPs, when released from Muller cells, may
      perform layer dependent functions.

PMID- 15246544
TI  - Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by
      doxorubicin on cerebellar granule neurons in mouse.
AB  - Cell cycle regulators such as cyclin-dependent kinases (Cdks) and their
      inhibitors (Ckis) have been reported to be involved in neuronal cell death (NCD)
      induced by a variety of insults such as ischemia, UV-irradiation, nerve growth
      factor (NGF)-withdrawal, and anticancer therapeutics. But their precise
      interactive regulation has still to be unveiled. In the present study, we focused
      on cell cycle regulators such as Cdk4, p21(WAF1) and p53 to clarify their
      regulatory mechanisms, using NCD induced by doxorubicin (D-NCD) in mouse
      cerebellar granule neurons as a model. Doxorubicin induced NCD in a dose
      dependent manner, a typical feature of apoptosis as determined by TUNEL assay.
      Doxorubicin increased the protein expression of p53 in time- and dose-dependent
      manners. The protein expression of p21(WAF1), a Cki of Cdk4, was stimulated by
      doxorubicin at low concentrations, but it disappeared at high concentrations.
      Doxorubicin activated the kinase activity of Cdk4 without the enhancement of Cdk4
      protein. 3-Amino-9-thio(10H)-acridone (3-ATA), the specific inhibitor of Cdk4,
      prevented D-NCD in a dose-dependent manner. Wortmannin, an inhibitor of ATM
      (ataxia telangiectasia, mutated) that has high homology with the phosphatidyl
      inositol-3-kinase (PI3K) family and has protein kinase activity for the induction
      of p53 with specificity for serine and threonine residues, inhibited the
      activation of Cdk4 without the induction of p53 in D-NCD. These data suggest that
      (1) Cdk4 is one of the essential components for inducing NCD, that (2) p53 may
      prevent D-NCD through the induction of p21(WAF1) at low concentrations of
      doxorubicin, and that (3) Cdk4 might be activated by the same signal-molecules,
      like ATM, that are necessary for the activation of p53 in D-NCD.

PMID- 15246546
TI  - Suppression of auditory cortical activities in awake cats by pure tone stimuli.
AB  - Based on the time courses of excitatory spike-responses to pure-tone stimuli,
      neurons in the primary auditory cortex (A1) of awake cats have been classified
      into the phasic cell (P-cell), the tonic cell (T-cell), and the phasic-tonic cell
      (PT-cell). In the present study, taking advantage of the presence of the
      spontaneous spike-activities of A1 neurons in awake animals, time courses of
      suppressive spike-responses to pure-tone stimuli were studied by constructing
      spectro-temporal spike-activity diagrams. In P-cell, the suppression and
      excitation temporally alternated and spectrally co-occurred, restricting
      excitatory spike-responses within narrow temporal limits but not setting the
      spectral limits. In T-cell, the suppression and excitation spectrally alternated
      and temporally co-occurred, restricting excitatory frequency-tuning but not
      setting the time limits. PT-cell has mixed response properties of P- and T-cells.
      The findings suggest that: (1) P-cell analyzes temporal information of the sound
      without active spectral limits, (2) T-cell analyzes spectral information without
      limits of time, and (3) PT-cell analyzes spectrally and temporally complex
      auditory information. Taken in the light of recent findings that the shift of the
      balance of the synaptic excitation and inhibition results in the spike-activity
      modulation of the cerebral cortical neurons, it is suggested that the temporal
      shift of the balance of the excitation and inhibition works in P-cell; the
      spectral shift, in T-cell; and the combination of the temporal and spectral
      shifts, in PT-cell, underlying the functional differences between cell-types.

PMID- 15246545
TI  - S100 protein is a useful and specific marker for hair cells of the lateral line
      system in postembryonic zebrafish.
AB  - The neuromast of the lateral line system of zebrafish has become an ideal model
      for the study of both developmental genetics and the vertebrate auditory system.
      Interestingly, the hair cells of this system have been found to selectively
      display immunoreactivity for S100 protein in some teleosts. In order to provide a
      selective marker for the sensory cells of the lateral line system, we have
      analyzed immunohistochemically the expression of S100 protein in zebrafish from
      the larval to the adult stage. In larval and adult animals S100 protein
      immunoreactivity was detected restricted to the hair cells of both superficial
      and canal neuromasts. Apparently the expression of S100 protein by hair cells was
      independent of the age, but it was expressed heterogeneously in the hair cells of
      canal neuromasts. The results of this work provide a feasible method to easily
      identify sensory cells in the neuromasts, and may be of interest in studies
      regarding development, differentiation or turnover of hair cells.

PMID- 15246547
TI  - Role of extracellular histidines in agonist sensitivity of the rat P2X4 receptor.
AB  - Relatively little information is available about the relationship between the
      molecular structure of each of the seven subtypes of P2X receptors and their
      function. Here, we investigated the possible function of three histidine residues
      in the extracellular loop of rat P2X(4) receptors. Mutation of histidine 241 to
      alanine (H241A) in the rat P2X(4) receptor decreased the EC(50) value of the ATP
      concentration-response curve from 8.4 to 0.7 microM. In contrast, the histidine
      mutation H140A or H286A slightly increased the EC(50) value. Maximal current
      responses were significantly larger in oocytes expressing rat H241A-mutated
      receptors compared to those expressing wildtype, H140A or H286A receptors. In
      addition, significantly less receptor protein was detected in H241A-expressing
      oocytes than in oocytes expressing wildtype, H140A or H286A receptors. Moreover,
      ATP-activated current in H241A-expressing cells activated faster than in wildtype
      receptor-expressing cells. The increased maximal current amplitude, the decrease
      in protein expression and the more rapid activation kinetics suggest that the
      H241A mutation facilitates opening of the receptor-channel (gating).

PMID- 15246548
TI  - GABA in pedunculo pontine tegmentum regulates spontaneous rapid eye movement
      sleep by acting on GABAA receptors in freely moving rats.
AB  - REM-OFF and REM-ON neurons in the brainstem are reported to regulate REM sleep,
      however, the detailed mechanism of generation of REM sleep is unknown. The former
      are continuously active except during REM sleep and an inhibitory
      neurotransmitter, GABA, has been implicated in mediating the inhibition for the
      generation of REM sleep. The REM-ON neurons, on the other hand, remain inactive
      throughout but increase firing during REM sleep. This study was conducted to
      investigate if GABA in the brain area rich in cholinergic REM-ON neurons would
      modulate REM sleep as proposed earlier. Rats were surgically prepared for sleep
      wake recording and two cannulae aiming pedunculopontine areas in the brainstem
      that are rich in REM-ON neurons, were implanted bilaterally. After recovery,
      picrotoxin, a GABA(A) antagonist, was simultaneously microinjected bilaterally
      into the pedunculopontine area in freely moving normally behaving rats using a
      remote dual syringe pump and the effects were studied on electrophysiological
      sleep and waking parameters. The results showed that picrotoxin significantly
      reduced REM sleep for 6h and the effect was due to reduction in the frequency of
      generation of REM sleep.

PMID- 15246549
TI  - The action of the insecticide imidacloprid on the respiratory rhythm of an
      insect: the beetle Tenebrio molitor.
AB  - Imidacloprid is an insecticide which has the nicotinic acetylcholine receptors
      (nAChRs) as its primary site of action; acetylcholine is the major excitatory
      neurotransmitter in the insect central nervous system (CNS). In this study, the
      action of imidacloprid was tested using the synapses of the respiratory central
      pattern generator of the beetle Tenebrio molitor. The no observed effect
      concentration (NOEC) for imidacloprid was estimated to be between 0.001 and 0.010
      microM. A concentration of 0.10 microM caused hyperexcitation in firing of the
      respiratory motoneurons, while the concentration of 1.00 microM caused an abrupt
      increase in their frequency and then a complete inhibition of the activity of the
      respiratory motoneurons. The possible implication of the action of such low
      concentrations of imidacloprid in the contraction of the respiratory muscles is
      also demonstrated and discussed.

PMID- 15246550
TI  - The effects of the electrical stimulation of the nasal mucosa on cortical
      cerebral blood flow in rabbits.
AB  - The cerebral vessels have sympathetic, parasympathetic, and sensory innervations.
      A sensory innervation of the cerebral vessels originating in the trigeminal
      ganglion has been described in a number of species by several investigations. It
      has been shown that the electrical stimulation of the trigeminal ganglion causes
      an increase of cerebral blood flow (CBF). The aim of our present study is to
      stimulate the trigeminal ganglion with an extracranial and non-invasive method. A
      stimulating electrode was put in the nasal mucosa via right nares of rabbits and
      trigeminal ganglion was stimulated orthodromically via nasociliary nerve (NCN).
      Variations in the cortical CBF were evaluated by laser Doppler flowmetry. In
      experiment group, CBF increased together with the beginning of electrical
      stimulation. The flow values were remained high as long as the stimulation. In
      post-stimulation period, the CBF was decreased gradually and returned to the
      baseline values at 120s. This study demonstrated that the electrical stimulation
      of the NCN branch of the trigeminal nerve increases the cortical CBF under
      physiological conditions.

PMID- 15246551
TI  - Tissue expression of 165-aa vascular permeability factor after spinal cord injury
      is not influenced by dexamethasone administration in rats.
AB  - Using immunohistochemistry, RT-PCR, and Western Blot techniques, we studied the
      tissue expression of the 165-aa Vascular permeability factor (VPF) after spinal
      cord injury (SCI) in adult Wistar rats. The results were compared according to
      that the animals received or non-dexamethasone, at the dose of 1mg/kg and day
      after trauma. Furthermore, the different functional recovery between treated and
      non-treated animals was recorded. Although the administration of dexamethasone
      showed a beneficial effect on the functional recovery of the animals, the tissue
      expression of VPF after SCI is not influenced by dexamethasone administration.
      Therefore, the neuroprotective effect of the dexamethasone after experimental SCI
      is not mediated through an interference on the biological effects of the 165-aa
      vascular permeability factor.

PMID- 15246552
TI  - Nerve growth factor-induced up-regulation of cytosolic phospholipase A2alpha
      level in rat PC12 cells.
AB  - Nerve growth factor (NGF) regulates various types of gene transcription in
      neurons. One of the cytosolic phospholipase A(2)s, cPLA(2)alpha, which
      preferentially cleaves phospholipids at the sn-2 position to arachidonic acid
      (AA), is involved in neuronal responses including survival. We investigated the
      effect of NGF on cPLA(2)alpha expression and its signaling pathways in PC12
      cells, which differentiate into neuronal-like cells with neurites by NGF
      treatment. Treatment with NGF increased cPLA(2)alpha mRNA level after 4h and its
      protein level 24h after NGF addition. The NGF-induced increase in cPLA(2)alpha
      mRNA was inhibited by actinomycin D. NGF caused phosphorylation of mitogen
      activated protein kinases (MAPKs); sustained phosphorylation of extracellular
      regulated kinases (ERK1/2) and transient phosphorylation of p38 MAPK. NGF
      responses (cPLA(2)alpha mRNA and its protein) were inhibited by selective
      inhibitors for the ERK1/2 pathway, p38 MAPK and c-Jun NH(2)-terminal kinase.
      Epidermal growth factor, which transiently activates ERK1/2, did not modify
      cPLA(2)alpha expression. Although phorbol 12-myristate 13-acetate, an activator
      of protein kinase C (PKC), alone showed no effect, NGF-induced cPLA(2)alpha mRNA
      expression decreased due to the inhibition of PKC. These findings suggest that
      NGF-induced cPLA(2)alpha expression is regulated by gene transcription via the
      ERK1/2, p38 MAPK and PKC pathways in PC12 cells.

PMID- 15246553
TI  - Regional cerebral blood volume reduction in transgenic mutant APP (V717F,
      K670N/M671L) mice.
AB  - Recent advance in nuclear magnetic resonance (NMR) microimaging has enabled in
      vivo cerebral blood volume (CBV) mapping with high spatial resolution. Using an
      intravascular susceptibility contrast agent and T(2)-weighted magnetic resonance
      imaging (MRI) on a 9.4T NMR microimager, the regional CBV was measured in mice as
      the transverse relaxation increase induced by the contrast agent. CBV maps in an
      Alzheimer's disease mouse model at resting state were obtained and examined. Four
      month-old male transgenic mutant APP (V717F, K670N/M671L) mice (N = 10) and
      littermate wild-type controls (N = 12) were used. Regional analysis of the multi
      slice CBV maps revealed statistically significant CBV reductions among the APP
      mice in cerebral cortex (-9.29%, P = 0.0002), hippocampus (-4.22%, P = 0.02), and
      thalamus (-5.21%, P = 0.03), indicating an early change of microvasculature in
      these selected regions. No significant difference was found in olfactory bulb,
      pons, midbrain, superior colliculus, medulla, and cerebellum.

PMID- 15246554
TI  - In vitro development of P- and R-like calcium currents in insect (Periplaneta
      americana) embryonic brain neurons.
AB  - Voltage-gated calcium currents are important for the survival and growth of
      embryonic cockroach brain neurons in primary culture. In the present experiments,
      we have studied, using the patch-clamp technique, the evolution with time in
      culture of the voltage-dependency and of the pharmacological properties of the
      calcium conductance of these neurons during the formation of a network. We have
      observed a progressive increase of the high-voltage-activated calcium conductance
      and a 10mV shift of the voltage-dependency of activation towards more negative
      potentials. The proportion of the R-like calcium current component increased
      during network formation. At the same time, the highly omega-AgaTxIVA-sensitive P
      like component of the current is progressively replaced by a component which is
      less sensitive to the toxin. The origin and functional implications of these
      modifications are discussed.

PMID- 15246555
TI  - Correlation of redox potentials and inhibitory effects on Epstein-Barr virus
      activation of 2-azaanthraquinones.
AB  - As a continuation of our studies using natural and synthetic products as cancer
      chemopreventive agents, we examined the standard redox potentials of some 2
      azaanthraquinones in phosphate buffer at pH 7.2 by means of cyclic voltammetry. A
      definite correlation has been found between the redox potentials and the
      inhibitory effects of the 2-azaanthraquinones on Epstein-Barr virus early antigen
      (EBV-EA) activation. It has been further shown that the correlation can be
      enhanced by introducing an electronic properties, i.e. the atomic charges at the
      C5 and O12 atoms in the quinone skeleton ring and the HOMO energy as additional
      parameters.

PMID- 15246556
TI  - Inhibition of cell cycle progression on HepG2 cells by hypsiziprenol A9, isolated
      from Hypsizigus marmoreus.
AB  - Antiproliferative activities of fractions of Hypsizigus marmoreus were examined
      using HepG2 cells in vitro. The methanol extract of H. marmoreus markedly induced
      antiproliferative activity, and an active compound from this mushroom was
      identified as hypsiziprenol A9. Hypsiziprenol A9 inhibited cell proliferation in
      a time- and concentration-dependent manner by up to 80% on HepG2 cells by
      inducing arrest of the G1 phase. Further investigation revealed that
      hypsiziprenol A9 decreased expression of phosphorylated retinoblastoma protein
      (ppRb), cyclin D1, and cyclin E in a dose-dependent manner. These results suggest
      that hypsiziprenol A9 can inhibit the growth of HepG2 cells through inducing G1
      phase cell cycle arrest due to the inhibition of pRb phosphorylation.

PMID- 15246557
TI  - Telomerase inhibition by sulfoquinovosyldiacylglycerol from edible purple laver
      (Porphyra yezoensis).
AB  - As high telomerase activity is detected in most cancer cells, telomerase
      represents a promising cancer therapeutic target. We investigated the inhibitory
      effect of sulfoquinovosyldiacylglycerol (SQDG), distributed in plants and
      seaweeds, on human telomerase in a cell-free system. SQDG inhibited telomerase
      activity dose-dependently with 50% inhibition at 22 microM, whereas
      monogalactosyldiacylglycerol and digalactosyldiacylglycerol did not, even at
      concentrations of 100 microM. Moreover, we confirmed that eicosapentaenoic acid,
      one of the fatty acid components of SQDG, is a potent telomerase inhibitor with
      50% inhibition at 19 microM. We speculate that the structure of the sulfate group
      and fatty acid of SQDG is important for the potent telomerase-inhibitory effect.
      Our findings suggest that SQDG has potential use as a therapeutic dietary
      compound for telomerase inhibition.

PMID- 15246558
TI  - Echinocystic acid induces apoptosis in HL-60 cells through mitochondria-mediated
      death pathway.
AB  - Echinocystic acid (EA) is a natural triterpone enriched in various herbs and used
      for medicinal purpose in many Asian countries. In the present study, we reported
      that EA can induce apoptosis in human promyelocytic leukemia cells (HL-60), as
      characterized by DNA fragmentation, poly (ADP) ribose polymerase cleavage. The
      efficacious induction of apoptosis was observed at 100 microM for 6 h. Further
      molecular analysis showed that EA induced the cleavage of Bid protein, the loss
      of mitochondrial membrane potential (DeltaPsim) cytochrome c release from
      mitochondria into cytosol, and activation of caspase-3, -8 and -9. However, EA
      did not generate reactive oxygen species (ROS), and antioxidants including N
      acetyl cysteine and catalase could not block EA-induced apoptosis in the HL-60
      cells. These data suggest that EA induces apoptosis in HL-60 cells through ROS
      independent mitochondrial dysfunction pathway.

PMID- 15246559
TI  - Enhanced TGFalpha-EGFR expression and P53 gene alterations contributes to gastric
      tumors aggressiveness.
AB  - We determined whether alterations in the expression of p53, p16(INK4) and
      p21(WAF1/CIP1) influence the invasiveness of a subset of gastric adenocarcinomas
      co-expressing TGFalpha and EGFR. Immunopositivity for TGFalpha-EGFR (26%) was
      observed in both early and advanced adenocarcinomas, and 88% of these showed
      immunoreactivity for p53. SSCP analysis revealed that in 81% of these tumors the
      p53 gene was mutated in exons 5-8. The intensity of p53 immunoreactivity was
      significantly higher (P < 0.013) in deeply invasive tumors. p16(INK4) and
      p21(WAF1/CIP1) immunoreactivity was detected in 93 and 76% of the samples co
      expressing TGFalpha-EGFR but the levels were not correlated with those of p53 and
      other clinico-pathological parameters. We conclude that gastric adenocarcinomas
      potentially dependent upon the TGFalpha-EGFR autocrine loop for growing exhibit
      increased aggressiveness in the presence of aberrant p53.

PMID- 15246560
TI  - The cyclin-dependent kinase inhibitor p21(cip1/waf1) enhances the cytotoxicity of
      ganciclovir in HSV-tk transfected ovarian carcinoma cells.
AB  - Suicide gene therapy could be an attractive addition to the treatment of ovarian
      carcinomas, for which acquired chemoresistance frequently results in treatment
      failure. Here we show that transfection of the HSV-tk gene, followed by
      incubation with up to 1 mM ganciclovir fails to induce cell death in SKOV3
      chemoresistant human ovarian carcinoma cells. However, co-transfection of HSV-tk
      with Cip1/Waf1 encoding the p21(cip1/waf1) inhibitor of cdks, allows 100 microM
      ganciclovir to eradicate the population of tumor cells. Potentiation of a drug by
      co-transfer of HSV-tk with Cip1/Waf1could thus represent another therapeutic
      approach for tumours that are resistant to conventional therapy.

PMID- 15246561
TI  - Acacetin-induced cell cycle arrest and apoptosis in human non-small cell lung
      cancer A549 cells.
AB  - In this study, we examined acacetin (5,7-dihydroxy-4'-methoxyflavone), a
      flavonoid compound, for its effect on proliferation in human non-small cell lung
      cancer A549 cells. The results first reported that acacetin not only inhibited
      A549 cell proliferation but also induced apoptosis and blocked cell cycle
      progression in the G1 phase. ELISA assay demonstrated that acacetin significantly
      increased the expression of p53 and p21/WAF1 protein, which caused cell cycle
      arrest. An enhancement in Fas and its two forms of ligands, membrane-bound Fas
      ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the
      apoptotic effect induced by acacetin. Taken together, p53 and Fas/FasL apoptotic
      system may participate in the antiproliferative activity of acacetin in A549
      cells.

PMID- 15246562
TI  - Up-regulation of Bfl-1/A1 via NF-kappaB activation in cisplatin-resistant human
      bladder cancer cell line.
AB  - The potent anti-cancer agent cis-diamminedichloroplatinum (II) (cisplatin) is
      currently used for treating bladder cancer. However, clinical use of this drug
      for long periods is often limited because of the appearance of cisplatin
      resistant bladder tumor cells. We employed the method of a differential display
      reverse transcriptase polymerase chain reaction to identify the differentially
      expressed genes in the parental human bladder cancer cell line, T24 and three
      cisplatin-resistant cell lines. We report here that cisplatin-resistant cell
      lines overexpress Bcl-2 family protein Bcl-2-related gene expressed in fetal
      liver (Bfl-1)/A1 as compared with their parental cell. Cisplatin and gamma
      irradiation induced expression of Bfl-1/A1 in T24R2 cells but not in T24 cells.
      Among Bcl-2 family members, Bfl-1/A1 showed the most significant alteration of
      the expression level in resistant cells. The nuclear translocation of nuclear
      factor-kappaB (NF-kappaB) by cisplatin and gamma-irradiation selectively occurred
      in T24R2 cells. Mitochondrial depolarization and cell death by cisplatin were
      also prevented in T24R2 cells. Moreover, Bfl-1/A1 inhibited cisplatin- and TNF
      alpha-induced apoptosis in BOSC23 cells. Our findings suggest that the induction
      of Bfl-1/A1 by NF-kappaB may be important in controlling resistance to cisplatin
      responses in bladder tumor cells.

PMID- 15246563
TI  - Effect of zinc-alpha2-glycoprotein (ZAG) on expression of uncoupling proteins in
      skeletal muscle and adipose tissue.
AB  - The plasma protein zinc-alpha2-glycoprotein (ZAG) has been shown to be identical
      with a lipid mobilizing factor capable of inducing loss of adipose tissue in
      cancer cachexia through an increased lipid mobilization and utilization. The
      ability of ZAG to induce uncoupling protein (UCP) expression has been determined
      using in vitro models of adipose tissue and skeletal muscle. ZAG induced a
      concentration-dependent increase in the expression of UCP-1 in primary cultures
      of brown, but not white, adipose tissue, and this effect was attenuated by the
      beta3-adrenergic receptor (beta3-AR) antagonist SR59230A. A 6.5-fold increase in
      UCP-1 expression was found in brown adipose tissue after incubation with 0.58
      microM ZAG. ZAG also increased UCP-2 expression 3.5-fold in C2C12 murine
      myotubes, and this effect was also attenuated by SR59230A and potentiated by
      isobutylmethylxanthine, suggesting a cyclic AMP-mediated process through
      interaction with a beta3-AR. ZAG also produced a dose-dependent increase in UCP-3
      in murine myotubes with a 2.5-fold increase at 0.58 microM ZAG. This effect was
      not mediated through the beta3-AR, but instead appeared to require mitogen
      activated protein kinase. These results confirm the ability of ZAG to directly
      influence UCP expression, which may play an important role in lipid utilization
      during cancer cachexia.

PMID- 15246564
TI  - Identification of differentially expressed genes in human lung squamous cell
      carcinoma using suppression subtractive hybridization.
AB  - Lung cancer is one of the major causes of cancer-related deaths. Over the past
      decade, much has been known about the molecular changes associated with lung
      carcinogenesis; however, our understanding to lung tumorigenesis is still
      incomplete. To identify genes that are differentially expressed in squamous cell
      carcinoma (SCC) of the lung, we compared the expression profiles between
      primarily cultured SCC tumor cells and bronchial epithelial cells derived from
      morphologically normal bronchial epithelium of the same patient. Using
      suppression subtractive hybridization (SSH), two cDNA libraries containing up-
      and down-regulated genes in the tumor cells were constructed, named as LCTP and
      LCBP. The two libraries comprise 258 known genes and 133 unknown genes in total.
      The known up-regulated genes in the library LCTP represented a variety of
      functional groups; including metabolism-, cell adhesion and migration-, signal
      transduction-, and anti-apoptosis-related genes. Using semi-quantitative reverse
      transcription-polymerase chain reaction, seven genes chosen randomly from the
      LCTP were analyzed in the tumor tissue paired with its corresponding adjacent
      normal lung tissue derived from 16 cases of the SCC. Among them, the IQGAP1,
      RAP1GDS1, PAICS, MLF1, and MARK1 genes showed a consistent expression pattern
      with that of the SSH analysis. Identification and further characterization of
      these genes may allow a better understanding of lung carcinogenesis.

PMID- 15246565
TI  - Antisense-mediated VEGF suppression in bladder and breast cancer cells.
AB  - Angiogenesis plays a key role in tumor growth and metastasis. Vascular
      endothelial growth factor (VEGF) is one of the major angiogenic factors. In the
      study we have evaluated the efficiency of antisense oligodeoxynucleotides (AS
      ODN) against VEGF selected from computational prediction of VEGF mRNA structure.
      Twenty-five different AS-ODN in two different tumor cell lines were investigated.
      Treatment of cell line EJ28 by VEGF723 resulted in a 83.5% suppression of VEGF
      protein when compared with control-ODN. Three further AS-ODN reduced VEGF protein
      more than 45% in comparison to control-ODN. This was caused by an antisense
      specific downregulation of the VEGF transcript determined by real-time PCR.
      Furthermore, antisense-mediated inhibition of VEGF was associated by a reduced
      cell viability. In MCF-7 cells VEGF protein was inhibited more than 45% by two AS
      ODN. In conclusion, we found that computational prediction of potential single
      strand mRNA motifs is a well suitable method to elect effective AS-ODN.

PMID- 15246566
TI  - Monitoring mitochondrial metabolisms in irradiated human cancer cells with
      (99m)Tc-MIBI.
AB  - Cationic hexakis(2-methoxyisobutylisonitrile)-technetium-99m ((99m)Tc-MIBI), an
      agent for scintigraphic detection and imaging of tumors, accumulates in
      mitochondria of various cells and tissues of high mitochondrial metabolic
      activity. To monitor the mitochondrial metabolisms of human cancer cells exposed
      to ionizing radiation, uptake of (99m)Tc-MIBI in an irradiated human lung cancer
      cell line (A549) was measured at 1-12 h following 0-9 Gy irradiation in vitro.
      Mitochondrial membrane potential, an index of mitochondrial activity, was also
      determined by flow cytometry with 3,3'-dihexyloxacarbocyanine (DiOC6(3)). At 1 h
      after 3 and 9 Gy irradiation, cellular (99m)Tc-MIBI accumulation increased by
      10.5 +/- 1.6 and 16.8 +/- 5.6% compared with controls, respectively (P < 0.01)
      DiOC6(3) measurement also showed increased mitochondrial membrane potentials
      immediately after irradiation, consistent with (99m)Tc-MIBI changes. The present
      findings showed that the transient hyperactivated mitochondrial metabolism and
      subsequently decreased activities following irradiation were monitored by
      determining the cellular (99m)Tc-MIBI accumulation, suggesting the possibility of
      (99m)Tc-MIBI scintigraphy as a functional imaging to monitor tumor metabolisms
      after radiation therapy.

PMID- 15246567
TI  - Elevated expression level of 60-kDa subunit of tRNA-guanine transglycosylase in
      colon cancer.
AB  - tRNA-guanine transglycosylase (TGT) is an enzyme which synthesizes a modified
      nucleoside, queuosine, by exchanging the base moiety of guanosine for queuine in
      tRNA. We have reported that the expression level of the 60-kDa subunit of TGT
      (TGT60kD) is elevated in leukemic cells, however, there is no other report on the
      expression of TGT60kD in cancer cells. The expression levels of the TGT60kD
      protein are elevated in four of the five colon cancer cell lines and 83% of colon
      cancer tissues compared with normal tissues. The expression levels of the TGT60kD
      protein decreased in two colon cancer cell lines, after cell differentiation was
      induced. A marked positive staining of cancer cells in colon tissues was
      observed, and the subcellular staining pattern was mainly cytosolic. These data
      suggest that the role of TGT60kD in colon carcinogenesis.

PMID- 15246568
TI  - Analysis of p53 mutations in cells taken from paraffin-embedded tissue sections
      of ductal carcinoma in situ and atypical ductal hyperplasia of the breast.
AB  - Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the
      implication of p53 mutations in breast cancer development remains poorly
      understood. In this study, we applied laser capture microdissection (LCM)
      microscope to histologically review and sample cells from paraffin-embedded
      breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS)
      and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected,
      using single stranded conformational polymorphism (SSCP) and sequencing, in cell
      samples of three cases with DCIS and five cases with ADH. p53 mutations are
      therefore present in DCIS and ADH of the breast, considered as pre-malignant
      precursors to breast cancer, and some of them may represent early events in
      breast cancer development.

PMID- 15246569
TI  - Modelling land use change and environmental impact.
AB  - Land use change models are tools for understanding and explaining the causes and
      consequences of land use dynamics. Recently, new models, combining knowledge and
      tools from biophysical and socio-economic sciences, have become available. This
      has resulted in spatially explicit models focussed on patterns of change as well
      as agent-based models focused on the underlying decision processes. These
      developments improve the use of land use change models in environmental impact
      studies. This special issue documents these developments: (i) analysing the
      system properties in a biophysical and socio-economic context at multiple scales;
      (ii) integrating spatially explicit land use change models in integrated
      assessment models; (iii) visualising and quantifying the potential effects of
      land use change in trade-off curves, to support land users and policy makers in
      their decisions; and (iv) modelling of the actual decision making process with
      agent-based modelling. A new promising future development is the incorporation of
      dynamic feedbacks between changing land use and changing environmental conditions
      and vice versa. Unfortunately such dynamic feedbacks between the socio-economic
      and biophysical model components are still not or only partially operational in
      current models and are therefore the most important challenge for land use and
      environmental modellers.

PMID- 15246570
TI  - First principles of the MameLuke multi-actor modelling framework for land use
      change, illustrated with a Philippine case study.
AB  - This paper presents the first principles of the MameLuke framework, an agent
      based modelling framework for studying environmental issues and land use and
      cover change (LUCC). The MameLuke framework enhances the understanding of the
      relationship between societal processes and LUCC by modelling individual and
      group decisions and human-environment interactions. The framework allows for the
      transformation of real-life stories into computerised models following a
      predetermined sequence. By doing so, the framework allows for a truly integrative
      approach, because it is not bound to any particular scientific discourse. Even
      better, the framework enables its users to combine scientific discourses
      regarding human decisions and behaviour on multiple scales and levels. The agents
      (actors and locations) in the framework are heterogeneous. This heterogeneity of
      agent behaviour is established by dividing the agents into categories. If an
      agent is a member of an agent category or combination of categories, it has
      access to a defined set of implementable actions. The actions are constructed out
      of potential option paths (POPs) and potential option nodes (PONs). The whole of
      POPs represent a theoretical construct of agent behaviour and decisions that the
      framework user wishes to explore. The POP defines a sequence of PONs. The PON is
      a transaction interface between an initialising agent and a recipient agent where
      they exchange material and immaterial capital. This paper explains the basic
      architecture of the MameLuke framework and shows its applicability with a model
      of a Philippine case study. This case study concerns the dynamics of migration
      and deforestation. It is part of a larger study on land use change in the San
      Mariano watershed area at the forest fringe of the Sierra Madre mountains in the
      Philippines.

PMID- 15246571
TI  - Trade-off analysis in the Northern Andes to study the dynamics in agricultural
      land use.
AB  - In this paper we hypothesize that land use change can be induced by non
      linearities and thresholds in production systems that impact farmers' decision
      making. Tradeoffs between environmental and economic indicators is a useful way
      to represent dynamic properties of agricultural systems. The Tradeoff Analysis
      (TOA) System is software designed to implement the integrated analysis of
      tradeoffs in agricultural systems. The TOA methodology is based on spatially
      explicit econometric simulation models linked to spatially referenced bio
      physical simulation models to simulate land use and input decisions. The
      methodology has been applied for the potato-pasture production system in the
      Ecuadorian Andes. The land use change literature often describes non-linearity in
      land use change as a result of sudden changes in the political (e.g. new
      agricultural policies) or environmental setting (e.g. earthquakes). However, less
      attention has been paid to the non-linearities in production systems and their
      consequences for land use change. In this paper, we use the TOA system to study
      agricultural land use dynamics and to find the underlying processes for non
      linearities. Results show that the sources of non-linearities are in the
      properties of bio-physical processes and in the decision making-process of
      farmers.

PMID- 15246572
TI  - Constructing land-use maps of the Netherlands in 2030.
AB  - The National Environmental Assessment Agency of the RIVM in the Netherlands is
      obliged to report on future trends in the environment and nature every 4 years.
      The last report, Nature Outlook 2, evaluated the effects of four alternative
      socio-economic and demographic scenarios on nature and the landscape. Spatially
      detailed land-use maps are needed to assess effects on nature and landscape. The
      objective of the study presented here was how to create spatially detailed land
      use maps of the Netherlands in 2030 using the Environment Explorer, a Cellular
      Automata-based land-use model to construct land-use maps from four scenarios. One
      of these is discussed in great detail to show how the maps were constructed from
      the various scenario elements, story lines and additional data and assumptions on
      national, regional and local land-use developments. It was the first time in the
      history of our outlooks that consistent, spatially detailed land-use maps of the
      Netherlands for 2030 were constructed from national economic and demographic
      scenarios. Each map represents a direct reflection of model input and
      assumptions. The maps do not show the most probable developments in the
      Netherlands but describe the possible change in land use if Dutch society were to
      develop according to one of the four scenarios. The large (societal)
      uncertainties are reflected in the total set of future land-use maps. The
      application of a land-use model such as the Environment Explorer ensures that all
      relevant aspects of a scenario, i.e. economic and demographic developments,
      zoning policies and urban growth, are integrated systematically into one
      consistent framework.

PMID- 15246573
TI  - A design and application of a multi-agent system for simulation of multi-actor
      spatial planning.
AB  - Multi-agent Systems (MAS) offer a conceptual approach to include multi-actor
      decision making into models of land use change. The main goal is to explore the
      use of MAS to simulate spatial scenarios based on modelling multi-actor decision
      making within a spatial planning process. We demonstrate MAS that consists of
      agents representing organizations and interest groups involved in an urban
      allocation problem during a land use planning process. The multi-actor based
      decision-making is modelled by generating beliefs and preferences of actors about
      the location of and relation between spatial objects. This allows each agent to
      confront these beliefs and preferences with it's own desires and with that of
      other agents. The MAS loosely resembles belief, desire and intentions
      architecture. Based on a case study for a hypothetical land use planning
      situation in a study area in the Netherlands we discuss the potential and
      limitations of the MAS to build models that enable spatial planners to include
      the 'actor factor' in their analysis and design of spatial scenarios. In
      addition, our experiments revealed the need for further research on the
      representation of spatial objects and reasoning, learning and communication about
      allocation problems using MAS.

PMID- 15246574
TI  - Multi-scale analysis of a household level agent-based model of landcover change.
AB  - Scale issues have significant implications for the analysis of social and
      biophysical processes in complex systems. These same scale implications are
      likewise considerations for the design and application of models of landcover
      change. Scale issues have wide-ranging effects from the representativeness of
      data used to validate models to aggregation errors introduced in the model
      structure. This paper presents an analysis of how scale issues affect an agent
      based model (ABM) of landcover change developed for a research area in the
      Midwest, USA. The research presented here explores how scale factors affect the
      design and application of agent-based landcover change models. The ABM is
      composed of a series of heterogeneous agents who make landuse decisions on a
      portfolio of cells in a raster-based programming environment. The model is
      calibrated using measures of fit derived from both spatial composition and
      spatial pattern metrics from multi-temporal landcover data interpreted from
      historical aerial photography. A model calibration process is used to find a best
      fit set of parameter weights assigned to agents' preferences for different
      landuses (agriculture, pasture, timber production, and non-harvested forest).
      Previous research using this model has shown how a heterogeneous set of agents
      with differing preferences for a portfolio of landuses produces the best fit to
      landcover changes observed in the study area. The scale dependence of the model
      is explored by varying the resolution of the input data used to calibrate the
      model (observed landcover), ancillary datasets that affect land suitability
      (topography), and the resolution of the model landscape on which agents make
      decisions. To explore the impact of these scale relationships the model is run
      with input datasets constructed at the following spatial resolutions: 60, 90,
      120, 150, 240, 300 and 480 m. The results show that the distribution of landuse
      preference weights differs as a function of scale. In addition, with the gradient
      descent model fitting method used in this analysis the model was not able to
      converge to an acceptable fit at the 300 and 480 m spatial resolutions. This is a
      product of the ratio of the input cell resolution to the average parcel size in
      the landscape. This paper uses these findings to identify scale considerations in
      the design, development, validation and application of ABMs of landcover change.

PMID- 15246575
TI  - The role of population in understanding Honduran land use patterns.
AB  - Land use patterns are usually influenced by large variety of factors that act
      over a broad range of scales. Biophysical, climatic, and socioeconomic factors
      are important and need to be considered, when distribution of land use is to be
      understood. The main objective of this study is to test this hypothesis using a
      statistical analysis at 'supra-local' level. Regression analysis is used to
      describe land use patterns in Honduras, selected because of its rare combination
      in Latin America of high population growth and poor biophysical conditions.
      Furthermore, the aim of the analysis is to specifically highlight two aspects,
      the effect of spatial and temporal scale and the influence of population density:
      to determine the influence of spatial and temporal scale, six spatial resolutions
      at two points in time (1974 and 1993) were included. To determine the role of
      population density and population growth, this factor was singled out; an
      analysis of migration patterns was performed; and a measure for technological
      development was calculated. Multiple regression equations indicate the importance
      of soil-related, climatic and demographic factors for most of the land uses.
      Relations appear to be stable in space and time. Rural population density
      dominates as driver over the whole range of resolutions and for both years,
      especially for maize where it explains up to 80% of the variation. The strong
      constant relationship between population and agricultural area could be caused by
      a lack of technological development. An analysis of yield development confirms
      that for most annual crops yield increases lag behind area growth. Besides, the
      strong correlation could be explained by assuming rural population density to be
      a proxy for a range of other factors, like labour costs, or accessibility that
      are the direct drivers of land use change. In any case, this study suggests that
      for a specific--relatively coarse--window of temporal and spatial scale, land use
      patterns can be described with very simple relationships, with a strong
      contribution of population density. More local studies are needed to test the
      hypothesis that rural population density is a proxy for other variables.

PMID- 15246576
TI  - Modelling land use change with generalized linear models--a multi-model analysis
      of change between 1860 and 2000 in Gallatin Valley, Montana.
AB  - This paper develops an approach to modelling land use change that links model
      selection and multi-model inference with empirical models and GIS. Land use
      change is frequently studied, and understanding gained, through a process of
      modelling that is an empirical analysis of documented changes in land cover or
      land use patterns. The approach here is based on analysis and comparison of
      multiple models of land use patterns using model selection and multi-model
      inference. The approach is illustrated with a case study of rural housing as it
      has developed for part of Gallatin County, Montana, USA. A GIS contains the
      location of rural housing on a yearly basis from 1860 to 2000. The database also
      documents a variety of environmental and socio-economic conditions. A general
      model of settlement development describes the evolution of drivers of land use
      change and their impacts in the region. This model is used to develop a series of
      different models reflecting drivers of change at different periods in the history
      of the study area. These period specific models represent a series of multiple
      working hypotheses describing (a) the effects of spatial variables as a
      representation of social, economic and environmental drivers of land use change,
      and (b) temporal changes in the effects of the spatial variables as the drivers
      of change evolve over time. Logistic regression is used to calibrate and
      interpret these models and the models are then compared and evaluated with model
      selection techniques. Results show that different models are 'best' for the
      different periods. The different models for different periods demonstrate that
      models are not invariant over time which presents challenges for validation and
      testing of empirical models. The research demonstrates (i) model selection as a
      mechanism for rating among many plausible models that describe land cover or land
      use patterns, (ii) inference from a set of models rather than from a single
      model, (iii) that models can be developed based on hypothesised relationships
      based on consideration of underlying and proximate causes of change, and (iv)
      that models are not invariant over time.

PMID- 15246577
TI  - Downscaling climate change scenarios in an urban land use change model.
AB  - The objective of this paper is to describe the process through which climate
      change scenarios were downscaled in an urban land use model and the results of
      this experimentation. The land use models (Urban Growth Model [UGM] and the Land
      Cover Deltatron Model [LCDM]) utilized in the project are part of the SLEUTH
      program which uses a probabilistic cellular automata protocol. The land use
      change scenario experiments were developed for the 31-county New York
      Metropolitan Region (NYMR) of the US Mid-Atlantic Region. The Intergovernmental
      Panel on Climate Change (IPCC), regional greenhouse gas (GHG) emissions scenarios
      (Special Report on Emissions Scenarios (SRES) A2 and B2 scenarios) were used to
      define the narrative scenario conditions of future land use change. The specific
      research objectives of the land use modeling work involving the SLEUTH program
      were threefold: (1) Define the projected conversion probabilities and the amount
      of rural-to-urban land use change for the NYMR as derived by the UGM and LCDM for
      the years 2020 and 2050, as defined by the pattern of growth for the years 1960
      1990; (2) Down-scale the IPCC SRES A2 and B2 scenarios as a narrative that could
      be translated into alternative growth projections; and, (3) Create two
      alternative future growth scenarios: A2 scenario which will be associated with
      more rapid land conversion than found in initial projections, and a B2 scenario
      which will be associated with a slower level of land conversion. The results of
      the modeling experiments successfully illustrate the spectrum of possible land
      use/land cover change scenarios for the years 2020 and 2050. The application of
      these results into the broader scale climate and health impact study is
      discussed, as is the general role of land use/land cover change models in climate
      change studies and associated environmental management strategies.

PMID- 15246579
TI  - Impact of informed consent requirements on cardiac arrest research in the United
      States: exception from consent or from research?
AB  - INTRODUCTION: Research in patients with life-threatening illness such as cardiac
      arrest is challenging since they can not consent. The Food and Drug
      Administration addressed research under emergency conditions by publishing new
      criteria for exception from informed consent in 1996. We systematically reviewed
      randomized trials over a 10-year period to assess the impact of these
      regulations. METHODS: Case-control study of published trials for cardiac arrest
      (cases) and atrial fibrillation (controls.) Studies were identified by using
      structured searches of MEDLINE and EMBASE from 1992 to 2002. Included were
      studies using random allocation in humans with cardiac arrest or atrial
      fibrillation prior to enrollment. Excluded were duplicate publications. Number of
      American trials, foreign trials and proportion of trials of American origin were
      compared by using regression analysis. Changes in cardiac arrest versus atrial
      fibrillation trials were calculated as risk differences. RESULTS: Of 4982
      identified cardiac arrest studies, 57 (1.1%) were randomized trials. The number
      of American cardiac arrest trials decreased by 15% (95% CI: 8, 22%) annually (P =
      0.05). The proportion of cardiac arrest trials of American origin decreased by
      16% (95% CI: 10, 22%) annually (P = 0.006). Of 5596 identified atrial
      fibrillation studies, 197 trials (3.5%) were randomized trials. The risk
      difference between cardiac arrest versus atrial fibrillation trials being of
      American origin decreased significantly (annual difference -5.8% (95% CI: -10, 
      0.1%), P = 0.03). INTERPRETATION: Fewer American cardiac arrest trials were
      published during the last decade, when federal consent requirements changed.
      Regulatory requirements for clinical trials may inhibit improvements in care and
      threaten public health.

PMID- 15246580
TI  - Measuring survival rates from sudden cardiac arrest: the elusive definition.
AB  - BACKGROUND: Measuring survival from sudden out-of-hospital cardiac arrest (OOH
      CA) is often used as a benchmark of the quality of a community's emergency
      medical service (EMS) system. The definition of OOH-CA survival rates depends
      both upon the numerator (surviving cases) and the denominator (all cases).
      PURPOSE: The purpose of the public access defibrillation (PAD) trial was to
      measure the impact on survival of adding an automated external defibrillator
      (AED) to a volunteer response system trained in CPR. This paper reports the
      definition of OOH-CA developed by the PAD trial investigators, and it evaluates
      alternative statistical methods used to assess differences in reported
      "survival." METHODS: Case surveillance was limited to the prospectively
      determined geographic boundaries of the participating trial units. The numerator
      in calculating a survival rate should include only those patients who survived an
      event but who otherwise would have died except for the application of some facet
      of emergency medical care-in this trial a defibrillatory shock. Among
      denominators considered were: total population of the study unit, all deaths
      within the study unit, and documented ventricular fibrillation cardiac arrests.
      The PAD classification focused upon cases that might have benefited from the
      early use of an AED, in addition to the likely benefit from early recognition of
      OOH-CA, early access of EMS, and early cardiopulmonary resuscitation (CPR).
      Results of this classification system were used to evaluate the impact of the PAD
      definition on the distribution of cardiac arrest case types between CPR only and
      CPR + AED units. RESULTS: Potential OOH-CA episodes were classified into one of
      four groups: definite, probable, uncertain, or not an OOH-CA. About half of
      cardiac arrests in the PAD units were judged to be definite OOH-CA events and
      therefore potentially treatable with an AED. However, events that occurred in CPR
      only units were less likely to be classified as definite or probable OOH-CA
      events than those in CPR + AED units (43% versus 55%, odds ratio 0.78, 95%
      confidence interval 0.57-1.07). The study retained sufficient power to permit a
      statistical analysis of the alternative hypothesis that the CPR + AED method
      results in twice as many survivors as a CPR-only approach. The result is
      critically dependent on the denominator used for calculating survival rates; but
      the analysis does not require a denominator as the numerators will have identical
      Poisson distributions (counts for rare events) under the null hypothesis since
      randomization distributes the risk of cardiac arrest evenly between the two arms.
      CONCLUSION: Reported OOH-CA rates and survival rates vary widely, depending upon
      the definitions applied to events. Rigorous assessment of treatments applied to
      improve survival can be obscured by inappropriate definitions. Large-scale
      randomized interventions designed to improve survival from OOH-CA can be
      evaluated based upon the absolute numbers of patients surviving, rather than a
      change in the proportion surviving.

PMID- 15246581
TI  - A predictive model for survival after in-hospital cardiopulmonary arrest.
AB  - BACKGROUND: In-hospital cardiopulmonary resuscitation (CPR) has seen a steady
      increase in the application of technology and techniques since the introduction
      of closed cardiac massage in 1960. Despite this progress, there has not been a
      demonstrated improvement in survival rates after in-hospital cardiac arrest over
      the last 40 years. Identification of prognostic factors associated with survival
      after a resuscitation attempt can help physician decisions and patients' end-of
      life choices in a pre-arrest situation. METHODS: Using an Utstein-based template
      we analyzed 219 consecutive adult attempted resuscitations in a large urban
      teaching hospital over a 3-year period. The main outcome measures were survival
      to discharge, 1 and 3 months. Backwards stepwise logistic regression was used to
      select baseline variables that predict survival at discharge, 1 and 3 months.
      RESULTS: Survival rates at discharge, 1 and 3 months were 15.1, 13.3, and 11.5%.
      Meaningful neurological status (cerebral performance score of 1) at discharge was
      achieved in 61% of survivors. Independent predictors of survival were: higher
      body-mass index (BMI), presence of chronic renal insufficiency (CRI), respiratory
      arrest, ventricular tachycardia/fibrillation (VT/VF) as initial rhythm and arrest
      early during the hospital stay. A risk model based on these variables
      demonstrated a significant fit between predicted and observed survival at
      discharge with goodness of fit test P-value of 0.87. CONCLUSIONS: Survival after
      in-hospital cardiopulmonary arrest is poor and can be estimated by using clinical
      variables. If validated in a large prospective trial, this score could help
      physicians in attempting resuscitation, patients and families in making end-of
      life decisions and hospitals in resource allocation.

PMID- 15246582
TI  - An assessment of public attitudes toward automated external defibrillators.
AB  - OBJECTIVE: We assessed the familiarity of the general public with automated
      external defibrillators (AEDs) and their willingness to use them. METHODS:
      Shoppers were asked to complete a survey in an AED-equipped suburban shopping
      mall. RESULTS: 359 surveys were analyzed. Of the participants, 11% were
      healthcare professionals, 51% had training in CPR or first aid, and 44% had no
      medical training. Sixty percent were able to define defibrillator adequately.
      Seventy-one percent stated they would be likely to use an AED to resuscitate a
      stranger. The most common concerns were fear of using the machine incorrectly
      (57%) and fear of legal liability (38%). After being told of liability protection
      from the federal Cardiac Arrest Survival Act, 84% stated they would be likely to
      use the AED. This increased further to 91% if the participants were given an
      opportunity to receive training. CONCLUSION: Although a substantial number of
      people in this setting were willing to use an AED, education regarding legal
      liability and proper use of the machines increased the reported likelihood of
      use. Further public education may be necessary to provide optimally effective
      public access defibrillation programs.

PMID- 15246583
TI  - Does attendance at an immediate life support course influence nurses' skill
      deployment during cardiac arrest?
AB  - OBJECTIVE: To determine if attendance at a Resuscitation Council (UK) immediate
      life support (ILS) course influenced the skill deployment of nurses at a
      subsequent cardiac arrests. METHODS: Data from all cardiac arrests occurring in
      two 12-month periods (before and 12 months after ILS course implementation) were
      collected. Semi-structured interviews were conducted with a sample of nurses who
      had completed ILS training within the past 12 months and who had subsequently
      attended a cardiac arrest. RESULTS: There were 103 patients defibrillated (after
      ILS implementation). Only one ward nurse defibrillated prior to the arrival of
      the crash team. There were 99 laryngeal mask airways (LMAs) inserted during the
      same period. Ward nurses performed two of these, one with the supervision of the
      resuscitation officer (RO). The interviews revealed that although many nurses
      felt confident after the course most felt that as time passed their confidence
      reduced to such a degree that they would not use their skills without
      supervision. Attendance at cardiac arrest soon after the course appeared to be a
      key element in maintaining confidence levels. CONCLUSION: ILS training alone may
      be insufficient to increase deployment of these skills by nurses who are not
      cardiac arrest team members. A more supportive approach, involving individual
      coaching of these individuals may need to be considered.

PMID- 15246584
TI  - Serum cortisol as a predictive marker of the outcome in patients resuscitated
      after cardiopulmonary arrest.
AB  - OBJECTS: To analyze the relationship between stress hormones (arginine
      vasopressin (ADH), adrenocorticotropic hormone (ACTH) and cortisol and the
      outcome of patients resuscitated after cardiopulmonary arrest (CPA). METHODS:
      Thirty-six patients were enrolled in this study. In 36 of the resuscitated cases,
      27 were non-survivors and 9 survived. The survival group was defined as cases
      either in a persistent vegetative state, with some disability or good recovery 1
      month after return of spontaneous circulation (ROSC). The non-survival group was
      defined as cases who died within 1 month. RESULTS: The plasma ADH and ACTH levels
      and the serum cortisol levels in both the surviving and the non-surviving
      patients were 82.3+/-74.5 and 149.6+/-135.4 (pg/ml), 239.7+/-327.4 and 282.4+/
      553.0 (pg/ml), 34.1+/-11.2 and 19.0+/-12.8 (g/ml) (mean+/-S.D., respectively).
      The plasma ADH and ACTH levels showed no significant difference between the two
      groups. The serum cortisol levels were significantly higher in survivors than in
      the non-survivors (P=0.029). We also used the receiving-operating characteristics
      (ROC) curves to evaluate the optimal cutoff value of the concentration of serum
      cortisol as a predictive maker of non-surviving patients. The cutoff value of
      16.7 g/ml for the concentrations of serum cortisol was a 1.00 positive predictive
      value and a 1.00 specificity at a 0.519 negative predictive and a 0.409
      sensitivity for predicting non-surviving patients. The area under the ROC curve
      was calculated to be 0.858 at a prevalence of 0.58. The plasma ADH levels
      correlated significantly and positively with the plasma ACTH levels (r=0.516,
      P<0.0010). CONCLUSIONS: We concluded that the serum cortisol levels were
      significantly higher in survivors than in non-survivors resuscitated after CPA.

PMID- 15246585
TI  - Vasopressin versus continuous adrenaline during experimental cardiopulmonary
      resuscitation.
AB  - OBJECTIVE: To evaluate the effects of a bolus dose of vasopressin compared to
      continuous adrenaline (epinephrine) infusion on vital organ blood flow during
      cardiopulmonary resuscitation (CPR). METHODS: Ventricular fibrillation was
      induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR
      was started. After 2 min of CPR the animals were randomly assigned to receive
      either vasopressin (0.4 U/kg) or adrenaline (bolus of 20 microg/kg followed by
      continuous infusion of 10 microg/(kg min)). Defibrillation was attempted after 9
      min of CPR. RESULTS: Vasopressin generated higher cortical cerebral blood flow (P
      < 0.001) and lower cerebral oxygen extraction (P < 0.001) during CPR compared to
      continuous adrenaline. Coronary perfusion pressure during CPR was higher in
      vasopressin-treated pigs (P < 0.001) and successful resuscitation was achieved in
      12/12 in the vasopressin group versus 5/12 in the adrenaline group (P = 0.005).
      CONCLUSIONS: In this experimental model, vasopressin caused a greater increase in
      cortical cerebral blood flow and lower cerebral oxygen extraction during CPR
      compared to continuous adrenaline. Furthermore, vasopressin generated higher
      coronary perfusion pressure and increased the likelihood of restoring spontaneous
      circulation.

PMID- 15246587
TI  - Percutaneous transcricoid jet ventilation compared with surgical
      cricothyroidotomy in a sheep airway salvage model.
AB  - BACKGROUND: We developed a large animal model of the "cannot intubate/cannot
      ventilate" (CNI/V) scenario to compare percutaneous transcricoid manual jet
      ventilation (MJV) with surgical cricothyroidotomy (SC). METHODS: Twelve sheep
      weighing 40-80 kg were assigned to MJV or SC groups. After sedation, intubation,
      and line placement, CNI/V was simulated by removing the tracheal tube and
      inducing paralysis with vecuronium. When SaO2 reached 80% (t=0), MJV catheter
      insertion or SC was initiated. Upon successful airway placement, ventilation
      began using 100% oxygen at 20 breaths/min. MJV was administered at 50 psi. HR,
      BP, SaO2, pH, PCO2, and PO2 were recorded at t=0, 30, 60, 90, 120, 150, 180, 300,
      600, and 1200 s. Data were reported as mean+/-S.E.M. over the whole observation
      period. Baseline values were compared using Student's t-tests. Repeated-values
      ANOVA was used for post-procedure group comparisons. Statistical tests were two
      tailed and alpha was set at 0.05. RESULTS: Body weights were not significantly
      (P=0.08) different between MJV (65+/-6 kg) and SC (52+/-3 kg) groups. Baseline
      respiratory and hemodynamic variables were also not significantly different.
      Median procedure time for MJV (20 s) and SC (24 s) was not significantly (P=0.69)
      different. Post-procedure values were not significantly different for SaO2
      (P=0.65), pH (P=0.70), PCO2 (P=0.47), PO2 (P=0.84), MAP (P=0.09), or HR (P=0.16)
      over the entire 20 min resuscitation period. CONCLUSION: Using a realistic model
      of CNI/V we found no difference in respiratory or hemodynamic variables between
      MJV and SC. Adequate ventilation and perfusion was maintained solely by MJV for
      up to 20 min.

PMID- 15246586
TI  - Antithrombin administration during experimental cardiopulmonary resuscitation.
AB  - OBJECTIVE: To determine whether antithrombin (AT) administration during
      cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced
      reperfusion injury. METHODS: Ventricular fibrillation was induced in 24
      anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The
      animals were randomised into two groups. The treatment group received AT (250
      U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation
      was attempted after 9 min of CPR. If restoration of spontaneous circulation
      (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood
      flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was
      calculated to reflect the relation between global cerebral circulation and oxygen
      demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro
      PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in
      jugular bulb plasma were performed to detect any signs of cerebral oxidative
      injury, inflammation and coagulation. RESULTS: There was no difference between
      the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels
      of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the
      control group reduction of AT began 15 min after ROSC and continued throughout
      the entire observation period (P < 0.05). Eicosanoids and TAT were increased
      compared to baseline in all animals (P < 0.01). CONCLUSIONS: In this experimental
      model of CPR, AT administration did not increase cerebral circulation or reduce
      reperfusion injury after ROSC.

PMID- 15246588
TI  - Effects of partial liquid ventilation on lipopolysaccharide-induced inflammatory
      responses in rats.
AB  - To determine whether partial liquid ventilation (PLV) modified lung inflammatory
      response, we analyzed blood cytokine levels and cytokine mRNA expression in the
      lungs, using a rat model of endotoxemia. Thirty-six rats were allocated into one
      of four groups. The first group received conventional gas ventilation (CV group),
      the second group received 10 ml/kg perflubron intratracheally in combination with
      mechanical gas ventilation (PLV group), the third group received 20 mg/kg
      Escherichia coli lipopolyssacharide (LPS) intravenously in combination with
      mechanical gas ventilation (LPS group), and the fourth group received PLV and LPS
      (PLV + LPS group). Blood levels of TNF-alpha, IL-1beta, IL-6, IL-10, INF-gamma
      and IL-1 receptor antagonist were significantly increased in LPS and PLV + LPS
      groups. mRNA expression of pro- and anti-inflammatory cytokines in the lung
      tissue was also significantly increased in these groups. mRNA expression of IL-6
      in PLV + LPS group was significantly increased in comparison with LPS group.
      Other cytokine mRNA expression including IL-10 and IL-1beta was also potentiated
      in PLV + LPS group, however this was not significant. Our results suggest that
      PLV does not protect the lungs against inflammation in systemic endotoxemia in
      rats.

PMID- 15246589
TI  - Global ischemic duration and reperfusion function in the isolated perfused rat
      heart.
AB  - Post-ischemic myocardial dysfunction has been observed in a variety of clinical
      situations including cardiac arrest. Potentially survivable cardiac arrest
      following short-term global myocardial ischemia may be of insufficient duration
      to cause irreversible myocyte injury, but still results in contractile and
      bioenergetic dysfunction. The purpose of this study was to characterize the
      ischemic transition from reversible to irreversible injury in the isolated
      perfused rat heart. Isolated, buffer perfused, male Sprague-Dawley rat hearts
      underwent normothermic ischemia of 15, 20, 25 or 30 min with or without 30 min of
      reperfusion and were freeze clamped in liquid nitrogen for bioenergetic analysis
      of LV tissue. Post-ischemic LV function and measurements of bioenergetic recovery
      were made between groups and with non-ischemic controls. Baseline LV function was
      similar in all groups. Post-ischemic contractile function was markedly depressed
      in the 25 and 30 min ischemia groups with persistent depression of high-energy
      phosphates, total adenine nucleotide pool, myocardial oxygen consumption,
      elevated CK release and evidence of significant mitochondrial edema in the 30 min
      group. In contrast with longer ischemic periods, the reduction in LV contractile
      function after 15 and 20 min of ischemia was mild, with more complete
      bioenergetic recovery, minimal CK release, and normal appearing mitochondrial.
      This data suggests a period of transition from reversible to irreversible injury
      occurring at approximately 20 min of normothermic global ischemia in the isolated
      perfused rat heart.

PMID- 15246590
TI  - Intraosseous infusions via the calcaneus.
AB  - OBJECTIVES: To demonstrate that intraosseous infusions via the calcaneus could
      deliver fluids to systemic veins and that intraosseous infusions do not require
      bones with medullary cavities. To demonstrate that intraosseous infusions could
      be successful in adults. DESIGN: Ten adult cadavers were injected with 16 gauge
      intraosseous needles and infused with 10 ml of methyl green dye at a
      concentration of 10 mg/ml. MAIN OUTCOME MEASURES: Observation of methyl green dye
      in the great saphenous, medial malleolar and dorsal veins of the foot recorded by
      digital photography on injection and at 1 min post-injection. RESULTS: Immediate
      entry of methyl green dye into the superficial veins of the leg was seen in 14
      out of the 20 legs trialled and delayed entry was noted in the two legs of
      another cadaver. No venous entry was seen in one cadaver and intraosseous access
      failed in one cadaver. CONCLUSIONS: Successful intraosseous infusions can be
      performed via the calcaneus. Intraosseous infusions can be successful in adult
      populations. While not a substitute for intraosseous infusions in other sites,
      the calcaneus provides an easily accessible site free of overlying vital
      structures.

PMID- 15246591
TI  - Successful thrombolysis after pulmonary embolectomy for persistent massive
      postoperative pulmonary embolism.
AB  - Massive postoperative pulmonary embolism (PE) is associated with a poor prognosis
      in patients presenting with haemodynamic instability. Since recent surgery is a
      commonly accepted contraindication for thrombolytic therapy, pulmonary
      embolectomy is an appropriate therapeutic approach in these patients. If life
      threatening symptoms of PE persist after pulmonary embolectomy, however, very few
      other therapeutic options are available. We report the successful use of locally
      administered low-dose thrombolysis 2 days after pulmonary embolectomy in a
      patient with postoperative PE and persistent severe hypoxaemia and pulmonary
      hypertension. During and after thrombolysis, no bleeding complications occurred.
      We conclude that low-dose thrombolysis for PE may be considered even in patients
      who have recently undergone major thoracic and abdominal surgery if embolectomy
      and continued intravenous heparin have failed to be successful and life
      threatening symptoms of PE persist.

PMID- 15246592
TI  - Hyperkalaemia causing loss of atrial capture and extremely wide QRS complex
      during DDD pacing.

PMID- 15246593
TI  - Cardiopulmonary resuscitation in prone position: a simplified method for
      outpatients.

PMID- 15246594
TI  - Respiratory arrest and the glucose state.

PMID- 15246595
TI  - Angular velocity: a new method to improve prediction of ventricular fibrillation
      duration.

PMID- 15246596
TI  - Systematic review of the effects of pertussis vaccines in children.

PMID- 15246598
TI  - Protection of mice against Friend retrovirus infection by vaccination with
      antigen-loaded, spleen-derived dendritic cells.
AB  - Antigen-loaded dendritic cells (DC) have been shown to induce specific immune
      responses in vivo. In the current study we used Friend virus (FV) as a model to
      analyze whether a DC vaccine is capable of inducing protective immunity against
      retroviral infections. Mice were vaccinated twice with spleen-derived DC loaded
      with FV antigen. All control mice that received DC without antigen developed
      progressive leukemia after FV challenge. In contrast, five of the 14 vaccines
      were protected against infection, three recovered from FV-induced disease, and
      only six progressed to lethal leukemia. Animals that progressed to disease had
      high viral loads in blood and spleen similar to the control mice. Virus-specific
      antibody responses were not induced by DC vaccination. In contrast, protection
      correlated with a vaccine-induced CD8+ T-cell response directed against an
      immunodominant epitope of FV. CD8+ T-cells were critical for the protective
      effect of the DC vaccine, since in vivo depletion of these cells from immunized
      mice prevented their protection. Our results demonstrate that antigen-loaded DC
      can induce specific cellular immune responses and prevent retrovirus-induced
      disease.

PMID- 15246599
TI  - Long-term antibody levels and booster responses in South African children
      immunized with nonavalent pneumococcal conjugate vaccine.
AB  - Children who had initially received three doses of either a nonavalent
      pneumococcal conjugate vaccine containing serotypes 1, 4, 5, 6B, 9V, 14, 18C,
      19F, and 23F or placebo at 6, 10, and 14 weeks of age were bled at 9 and 18
      months for determination of antibody concentrations. The children were then
      randomized to receive a booster dose of either the 9-valent pneumococcal
      conjugate vaccine or a 23-valent polysaccharide vaccine and antibody levels
      determined 1 month later. At 9 months, the geometric mean concentrations (GMCs)
      were significantly higher for all vaccine serotypes in vaccinated children
      compared with controls (means varied from 0.49 microg/ml for serotype 4 to 2.37
      microg/ml for serotype 14). At 18 months, antibody concentrations remained
      significantly higher in vaccinated children (means varied from 0.19 microg/ml for
      serotype 4 to 1.1 microg/ml for serotype 14). In children who had received
      conjugate vaccine in infancy, the conjugate vaccine at 18 months produced a
      significant booster response for serotypes 1, 6B, 14, 19F, and 23F (means varied
      from 2.74 microg/ml for serotype 19F to 15.52 microg/ml for serotype 6B) and
      produced a comparable response to a first dose of conjugate at this age for
      serotypes 4, 5, 9V, and 18C. Boosting at 18 months with polysaccharide vaccine
      produced higher antibody concentrations to all serotypes in children who had
      previously received conjugate vaccine compared to children who had not received
      the conjugate vaccine in infancy. In conclusion, the 9-valent pneumococcal
      conjugate vaccine given in infancy elicits significant and long-lasting antibody
      responses which can be boosted with either the conjugate or polysaccharide
      vaccines.

PMID- 15246600
TI  - Immunization with PfEMP1-DBL1alpha generates antibodies that disrupt rosettes and
      protect against the sequestration of Plasmodium falciparum-infected erythrocytes.
AB  - A family of parasite antigens known as Plasmodium falciparum erythrocyte membrane
      protein 1 (PfEMP1) is believed to play an important role in the binding of
      infected erythrocytes to host receptors in the micro-vasculature. Available data
      advocates the existence of a subset of very adhesive (rosetting, auto
      agglutinating) and antigenic PfEMP1s implicated as virulence factors. Serum
      antibodies that disrupt rosettes are rarely found in children with severe malaria
      but are frequent in those with mild disease suggesting that they may be
      protective. Here we have developed a Semliki forest virus (SFV) vaccine construct
      with a recombinant gene (mini-var gene) encoding a mini-PfEMP1 (DBL1alpha-TM-ATS)
      obtained from a particularly antigenic and rosetting parasite (FCR3S1.2). The
      mini-PfEMP1 is presented to the host mimicking the location of the native
      molecule at the infected erythrocyte surface. Antibodies generated by a regimen
      of priming with SFV RNA particles and boosting with a recombinant protein
      recognize the infected erythrocyte surface (immuno-fluorescence/rosette
      disruption) and prevent the sequestration of P. falciparum-infected erythrocytes
      in an in vivo model of severe malaria. The data prove the involvement of
      DBL1alpha in the adhesion of infected- and uninfected erythrocytes and the role
      of rosette-disruptive antibodies in preventing these cellular interactions. The
      work supports the use of DBL1alpha in a vaccine again severe malaria.

PMID- 15246601
TI  - Outbreak of mumps in a vaccinated child population: a question of vaccine
      failure?
AB  - In Belgium, children are immunized against measles-mumps-rubella (MMR) in a two
      dose schedule at the age of 15 months and 11 years. Despite these
      recommendations, epidemics of mumps still occur. During an outbreak of mumps in
      Bruges (Belgium), 105 cases were registered in seven schools (age group 3-12
      years). Lower than optimal vaccination coverage, inadequate vaccination schedule
      and a combination of primary and/or secondary vaccine failure are considered as
      possible reasons for the outbreak as described in the article. The role of
      secondary vaccine failure is highlighted.

PMID- 15246602
TI  - Recombinant ovine atadenovirus induces a strong and sustained T cell response
      against the hepatitis C virus NS3 antigen in mice.
AB  - Ovine atadenovirus (OAdV) is a novel gene transfer vector with excellent in vivo
      gene transfer characteristics. In the present study, we have investigated the
      ability of an OAdV vector to mediate a T cell response to an antigen of the
      hepatitis C virus (HCV) in mice. Specifically, an expression cassette coding for
      non-structural protein 3 (NS3) of hepatitis C virus was inserted into the OAdV
      genome and the resulting recombinant virus (OAdV-ns3) was shown to propagate
      stably and to express the ns3 gene at a high level in vitro. A single injection
      of this non-replicating vector into BALB/c mice resulted in a strong induction of
      NS3-specific, IFN-gamma secreting T-lymphocytes as measured by direct ex vivo
      ELISpot assay. The number of IFN-gamma secreting lymphocytes remained nearly
      unaltered for a period of at least 10 weeks. The immune response was shown to
      depend on virus dose but a single intramuscular injection of less than 10(8)
      infectious particles of OAdV-ns3 was sufficient to induce a significant NS3
      specific T cell response. Moreover, this response was not affected by prior
      immunisation of animals with human adenovirus type 5 (HAdV-5). The results of our
      study provide proof for the concept that OAdV vectors may be valuable tools for
      vaccination and immunotherapy even in the face of natural immunity to human
      adenoviruses.

PMID- 15246604
TI  - The incidence of varicella in southern Taiwan: a life table method estimation
      among susceptible population.
AB  - Previous studies have failed to estimate the size of population at risk and
      underestimated the incidence of varicella among susceptible population. In this
      study, we calculated the incidence of varicella and its complications in Taiwan
      based on a life table method, in which the size of population at risk was taken
      into account. Population-based data were obtained from the Bureau of National
      Health Insurance. The age-specific incidences estimated by the uncorrected and
      corrected methods were compared. The incidence of varicella increased sharply
      after infancy and peaked at 16.7% in children aged 5 years. A correction which
      assumes the introduction of varicella vaccine resulted in a higher incidence of
      19.5% in children aged 5 years. The lifetime cumulative incidence increased to
      around 76%. Sensitive surveillance of varicella and correct incidence estimate
      among susceptible population are essential in countries that have implemented or
      are about to implement varicella vaccination.

PMID- 15246603
TI  - Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial
      neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV
      16/18 E6E7).
AB  - Heterologous prime-boost vaccination schedules employing TA-HPV, a vaccinia virus
      encoding HPV 16/18 E6 and E7, in combination with TA-CIN, an HPV 16 L2E6E7 fusion
      protein, may offer advantages over the use of either agent alone for the
      immunotherapy of human papillomavirus (HPV) type 16-associated vulval
      intraepithelial neoplasia (VIN). In the present study, 10 women with HPV 16
      positive high grade VIN, previously primed with TA-HPV, received three booster
      immunisations with TA-CIN. All but one demonstrated HPV 16-specific proliferative
      T-cell and/or serological responses following vaccination. Three patients
      additionally showed lesion shrinkage or symptom relief, but no direct correlation
      between clinical and immunological responses was seen.

PMID- 15246605
TI  - Development of antibodies against pneumococcal proteins alpha-enolase,
      immunoglobulin A1 protease, streptococcal lipoprotein rotamase A, and putative
      proteinase maturation protein A in relation to pneumococcal carriage and Otitis
      Media.
AB  - Surface associated pneumococcal proteins alpha-enolase (Eno), immunoglobulin A1
      protease (Iga), streptococcal lipoprotein rotamase A (SlrA), and putative
      proteinase maturation protein A (PpmA) have potential as candidates for future
      protein-based anti-pneumococcal vaccines. The immunogenicity of these proteins
      were studied in a cohort of 329 children during their first two years of life.
      During the first recorded episode of otitis media, acute and convalescent phase
      sera were available from 151 children. Concentrations of antibodies against Eno,
      Iga, SlrA and PpmA were measured by EIA and detected in 99% (300/302), 95%
      (288/302), 95% (288/302), and 83% (251/302) of the sera, respectively. There were
      no statistically significant differences between the groups of children with and
      without a history of pneumococcal contact or with respect to the type of
      pneumococcal contact. Despite a mean overall decrease in the antibody titers in
      the convalescent sera following AOM, several children were able to respond with a
      more than twofold increase in antibody titer in response to AOM. The majority of
      the children with increased antibody concentrations appeared in the groups, which
      were colonized with pneumococci at the time of serum collection, but were
      recorded as having no prior contact with pneumococci. In conclusion, SlrA, PpmA,
      Eno and Iga are immunogenic proteins that elicit antibody responses early in
      life. No significant correlation between antibody titers to these proteins and
      pneumococcal carriage or infection was found. Presumably, this results from the
      presence of cross-reactive epitopes on commensal bacteria.

PMID- 15246606
TI  - Persistence of protective immunity following vaccination against tick-borne
      encephalitis--longer than expected?
AB  - A descriptive evaluation of protective immunity was performed on subjects with a
      complete primary tick-borne encephalitis (TBE) immunization (and additional
      regular boosters) more than 3 years after primary or booster TBE immunization, as
      measured by neutralization test and two different ELISA systems. The study
      population (n = 430) was stratified for age (i.e., 18-49 or 50 years of age) and
      for the number of years since last TBE vaccination. GMTs (NT) of all subgroups
      (at the time of the present evaluation) were above detection limit: 144 and 44
      for the 18-49- and 50-year-old subjects, respectively. One percent of subjects
      aged 18-49 years, and 6% of subjects aged 50 years were ELISA-negative. A
      detailed sub analysis revealed that subjects with either low NT and/or negative
      to borderline ELISA test results are usually older and constitute a higher number
      of subjects without any TBE booster vaccination compared to the respective test
      positive subject group. From the fourth year (exceeding 3 years after last
      vaccination) titers show a decline rate of 6-7%. This study indicates that after
      multiple TBE (booster) immunizations protection surpasses the currently advised
      TBE booster interval of 3 years, thus supporting reconsideration of the
      recommendations for booster intervals.

PMID- 15246607
TI  - Identification of novel immunogenic proteins of Shigella flexneri 2a by proteomic
      methodologies.
AB  - Shigella spp. are one of the most important etiological factors for people who
      are living in developing countries and travelers to tropical countries. High
      priority has been given by the World Health Organization to the development of
      vaccines to control Shigellosis caused by these bacteria. However, information
      regarding to profile of immunogenic proteins of Shigella is not available now. In
      the present study, sub-immunoproteomics was applied to screen novel immunogenic
      proteins which could be reacted with antisera produced by challenge of a whole
      bacterium. Our results indicated that 13 immunogens were identified, in which
      seven proteins and six proteins from outer membrane and soluble proteome,
      respectively. Of the 13 proteins, 12 showed to be novel immunogens. These results
      suggest that immunoproteomics can greatly improve the chances of identification
      and result in discovery of novel immunogenic proteins.

PMID- 15246608
TI  - Limited infection upon human exposure to a recombinant raccoon pox vaccine
      vector.
AB  - A laboratory accident resulted in human exposure to a recombinant raccoon
      poxvirus (RCN) developed as a vaccine vector for antigens of Yersinia pestis for
      protection of wild rodents (and other animals) against plague. Within 9 days, the
      patient developed a small blister that healed within 4 weeks. Raccoon poxvirus
      was cultured from the lesion, and the patient developed antibody to plague
      antigen (F1) and RCN. This is the first documented case of human exposure to RCN.

PMID- 15246609
TI  - Maturation of dendritic cells by bacterial immunomodulators.
AB  - Dendritic cells (DC) become fully functional upon maturation by various stimuli.
      We tested whether an immunostimulatory effect of clinically used immunomodulators
      (Luivac, Biostim, Ribomunyl, Imudon, Bronchovaxom) is caused by direct DC
      activation. We found that Luivac, Biostim and Ribomunyl have a very high DC
      stimulatory potential in vitro. The level of DC activation was comparable or
      higher than DC maturation induced by standard maturation stimuli, Poly (I:C) or
      lipopolysaccharide. Treated DC had activated phenotype, reduced phagocytic
      activity and they induced the proliferation of allogeneic T lymphocytes. These
      results are important for understanding the physiology of action of these widely
      prescribed agents. Administration of bacterial immunomodulators should be
      considered with care to avoid the potential risk of inducing an autoimmune
      disease. They could also be used as well-defined maturating agents in the
      protocols used for the ex vivo production of DC-based vaccines for clinical
      trials.

PMID- 15246610
TI  - Human airway epithelial cells present antigen to influenza virus-specific CD8+
      CTL inefficiently after incubation with viral protein together with ISCOMATRIX.
AB  - In the present paper, an in vitro model was established in which the interaction
      between influenza virus-specific CD8+ T cells and human airway epithelial cells
      can be studied. To this end, the human lung epithelial cell line A549 was
      transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the
      presentation of the immunodominant M158-66 cytotoxic T lymphocyte (CTL) epitope
      of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell
      clone specific for the M158-66 epitope were used to evaluate ISCOMATRIX (IMX),
      which is considered a potential mucosal adjuvant for influenza vaccines, for its
      capacity to activate virus-specific CTL after incubation with epithelial cells.
      It was found that virus infected epithelial cells activated virus-specific CTL
      efficiently. However, incubation of epithelial cells with ISCOMATRIX and
      recombinant M1 protein activated CD8+ T cells inefficiently, unlike the
      incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B
      lymphoblastoid cells with these reagents. It was concluded that this lack of
      antigen presentation by epithelial cells indicate that these cells are not
      subject to killing by virus-specific CTL upon instillation with ISCOMATRIX-based
      vaccines, which may be a favorable property of mucosal vaccines.

PMID- 15246611
TI  - Immunogenicity in mice of a cationic microparticle-adsorbed plasmid DNA encoding
      Japanese encephalitis virus envelope protein.
AB  - Previously, we described a plasmid pMEa, synthesizing the anchored form of
      Japanese encephalitis virus (JEV) envelope protein that generated virus
      neutralizing antibodies in mice upon intra-muscular injection. The immunized mice
      showed significant protection against lethal JEV challenge. In order to improve
      the efficacy of plasmid DNA immunization against JEV, methods need to be employed
      that would enhance neutralizing antibody titers. Plasmid DNA adsorbed to cationic
      microparticles has recently been shown to significantly improve its
      immunogenicity. In the present study, we have adsorbed the plasmid pMEa on
      cationic microparticles and have compared its immunogenicity with the naked
      plasmid DNA. As seen in ELISA, the microparticle-adsorbed DNA induced higher
      titers of anti-JEV antibodies when compared to those induced by the naked DNA. No
      difference, however, was seen in JEV neutralization titers. The microparticle
      adsorbed DNA induced a mixed Th1-Th2 kind of immune responses as opposed to Th1
      type of immune responses elicited by the naked DNA.

PMID- 15246612
TI  - Identification and assessment of new vaccine candidates for group A streptococcal
      infections.
AB  - Group A Streptococcus (GAS) is a human-specific pathogen responsible for a wide
      variety of human diseases. Numerous GAS surface antigens interact with the human
      immune system and only some of these proteins have been studied in depth. A few
      of these may elicit protective response against GAS infection. In this study, we
      have used an in silico approach to identify antigenic peptides from GAS surface
      proteins. Putative GAS surface proteins from the M1 GAS genome were identified by
      the presence on LPxTG cell-wall anchoring motif and an export signal sequence.
      This technique identified 17 proteins of known or putative function, and another
      11 which do not have known homologues. Peptides derived from predicted antigenic
      sequences near the amino terminus of six of these proteins, and another seven
      peptides derived from the two known surface proteins, GRAB and MtsA, were
      conjugated to keyhole lymphocyanin (KLH), and investigated for their capacity to
      induce opsonic antibody responses in outbred Quackenbush mice. All peptide-KLH
      antisera demonstrated opsonic capacity against both 88/30 and M1 GAS. However,
      KLH sera alone was also able to induce opsonic antibodies, suggesting that anti
      KLH antibodies contributed to the opsonisation seen in the peptide-KLH antisera.
      KLH is therefore a promising carrier molecule for potential GAS peptide vaccines.

PMID- 15246613
TI  - Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four
      Pacific Island countries.
AB  - The prevalence rate of hepatitis B virus (HBV) infection in Pacific Island
      countries is amongst the highest in the world. Hepatitis B immunisation has been
      incorporated into national programmes at various times, often with erratic supply
      and coverage, until a regionally co-ordinated programme, which commenced in 1995
      ensured adequate supply. The effectiveness of these programmes was recently
      evaluated in four countries, Vanuatu and Fiji in Melanesia, Tonga in Polynesia
      and Kiribati in Micronesia. That evaluation established that the programmes had a
      substantial beneficial impact in preventing chronic hepatitis B infection
      [Vaccine 18 (2000) 3059]. Several studies of hepatitis B vaccination programmes
      in endemic countries have identified the potential significance of surface gene
      mutants as a cause for failure of immunisation. In the study outlined in this
      paper, we screened infected children and their mothers for the emergence and
      prevalence of these variants in specimens collected from the four country
      evaluation. Although the opportunity for the emergence of HBV vaccine escape
      mutants in these populations was high due to the presence of a considerable
      amount of the virus in the population and the selection pressure from vaccine
      use, there were no "a" determinant vaccine escape mutants found. This suggests
      that vaccine escape variants are not an important cause for failure to prevent
      HBV transmission in this setting. Other HBsAg variants were detected, but their
      functional significance remains to be determined. The failure to provide
      satisfactory protection during such immunisation programmes reflects the need for
      achieving and sustaining high vaccine coverage, improving the timeliness of doses
      as well as improving 'cold-chain' support, rather than the selection of vaccine
      escape mutants of HBV.

PMID- 15246614
TI  - Insertional mutagenesis of ricin A chain: a novel route to an anti-ricin vaccine.
AB  - The insertion of a specific 25-residue internal peptide into ricin toxin A chain
      (RTA) reduced the catalytic activity of this protein approximately 300-fold.
      Directed proteolytic cleavage of the peptide insert essentially restored
      catalytic activity of the resulting two peptide A chain to normal levels. Ricin
      holotoxin containing unprocessed mutant A chain was not toxic to cultured
      mammalian cells, due to enhanced proteasomal degradation, nor was it toxic when
      injected into rats at a concentration that is lethal in the case of native ricin.
      Rats treated in this way were completely resistant to native ricin when
      subsequently challenged with a potentially lethal dose of the toxin. These ricin
      resistant animals had a significant anti-ricin antibody titer, indicating that
      this approach has potential for developing an effective vaccine against this
      toxin.

PMID- 15246615
TI  - Influenza and pneumococcal vaccination of the elderly in Taiwan.
AB  - In 1998, Taiwan became the first country in Asia to provide free influenza
      vaccination to high-risk groups, mainly the elderly. The purpose of this study is
      to determine: (1) the annual mortality rate from influenza and pneumococcal
      related illnesses such as pneumonia, chronic bronchitis, pulmonary emphysema and
      asthma and (2) the effectiveness of and adverse events associated with the
      influenza vaccination. In the elderly, influenza vaccination caused the annual
      death rate due chronic bronchitis, pulmonary emphysema, and asthma to decline
      steadily but had no effect on the annual pneumonia death rate. The only adverse
      effect of concern was vertigo (in approximately 2-3%).

PMID- 15246616
TI  - Separation and characterization of adjuvant oligosaccharide oleate ester derived
      from product mixture of mannitol-oleic acid esterification.
AB  - Nearly 30 years after intense investigations of mannide monooleates for use as
      vaccine adjuvants, a novel adjuvant-active saccharide oleate ester was isolated
      and identified from the product mixture synthesized from mannitol and oleic acid.
      The mixture, which contained many kinds of mannide mono- and dioleates and their
      derivatives, was fractionated by liquid chromatography (LC), and the fraction
      with the highest adjuvanticity was obtained. Gel permeation chromatography (GPC)
      showed that it consisted of one major compound with an average molecular weight
      (MW) 2850. Infrared (IR) absorption and proton nuclear magnetic resonance spectra
      suggested it had oligosaccharide moieties and oleate domains. These findings
      suggested that it was an oligosaccharide oleate ester of the average MW 2850. The
      molecular ratio of oleate chains per monosaccharide unit was approximately 0.8.
      The ester induced both IgG1 and IgG2a antibody responses in mice in a dispersed
      form without base oil. This ester thus appears to be one of the adjuvant-active
      compounds largely contributing to the excellent adjuvanticity of mannide oleate
      mixture broadly used as vaccine emulsifier. These results and previous findings
      suggest that the fundamental adjuvanticity of this 'oligo' saccharide acylate
      ester was in accord with the hydrophil-lipophil balance (HLB) theory, similarly
      to other saccharide acylate esters. It is now expected that this compound will be
      useful as novel vaccine adjuvant which may induce both Th1 and Th2 type immune
      responses with low or no toxicity, not only as an vaccine emulsifier but in an
      aqueous suspension form.

PMID- 15246617
TI  - Breaking new ground--are changes in immunization services needed for the
      introduction of future HIV/AIDS vaccines and other new vaccines targeted at
      adolescents?
AB  - A safe, effective and accessible preventive vaccine is our best long-term hope
      for the control of the HIV/AIDS pandemic. Once the first generation of HIV
      vaccines are developed, many questions remain unanswered regarding their
      administration. For instance, which vaccines should be given to whom at what age
      and how many doses? We argue that pre- and early-adolescents will be one of the
      main target groups for future HIV vaccines, that is, before the age of exposure
      to the virus. Historically, immunization has mainly focused on infants. Indeed,
      vaccines have only occasionally been systematically targeted at adolescents, even
      in industrialized countries. Delivering vaccines to pre-adolescents and
      adolescents in developing countries would, to a great extent, be a new challenge.
      But it is not just HIV/AIDS vaccines that are coming down the pipeline. Herpes
      simplex type2 (HSV-2) and human papillomavirus (HPV) vaccines are also among the
      exciting candidate vaccines that may be the agents of change needed to encourage
      even the poorest countries to develop strategies for reaching adolescents with
      vaccines and other health services in the coming decade. Together, they may also
      provide the impetus for changing the paradigm for how vaccines are administered.
      Not only will more antigens be included in national immunization schedules, but
      the age of target groups will range much more widely than at present,
      encompassing older children, adolescents and young adults. While presenting major
      difficulties for delivery, these new ingredients also offer stimulating
      opportunities to completely rethink how vaccines are presented, administered and
      delivered. We predict that even the poorest countries will be looking to
      developing integrated, sustainable strategies for reaching pre-adolescents and
      adolescents with vaccines in the coming decade.

PMID- 15246618
TI  - Development and evaluation as vaccines in mice of Brucella melitensis Rev.1
      single and double deletion mutants of the bp26 and omp31 genes coding for
      antigens of diagnostic significance in ovine brucellosis.
AB  - The live attenuated Brucella melitensis Rev.1 strain is considered the best
      vaccine available for the prophylaxis of brucellosis in sheep caused by either B.
      melitensis or Brucella ovis. However, its application stimulates antibody
      responses in vaccinated animals indistinguishable by the current conventional
      serological tests from those observed in infected animals. The periplasmic
      protein BP26 and the outer membrane protein (OMP) Omp31 are immunodominant
      antigens in the serological responses of B. melitensis and B. ovis infected
      sheep, respectively. Accordingly, vaccine strain Rev.1 single and double deletion
      mutants of the bp26 and omp31 genes were developed, based on the principle that
      the use of such mutants as vaccines in association with diagnostic tests based on
      BP26 and Omp31 antigens would allow the serological differentiation between
      infected and vaccinated animals. The deletion mutants obtained were
      indistinguishable from the parental Rev.1 strain by conventional bacteriological
      and typing tests. The expression of their major surface antigens, as determined
      by reactivity with specific monoclonal antibodies (MAbs), remained unaffected,
      i.e. smooth-lipopolysaccharide (S-LPS) and OMPs besides in the expression of the
      antigens whose respective genes were deleted. The bp26 and omp31 deletions did
      not modify the kinetics of splenic infection nor the residual virulence of Rev.1
      in the BALB/c mouse model. Vaccination of BALB/c mice with the deletion mutants
      conferred significant protective immunity against B. melitensis strain H38 or B.
      ovis strain PA challenges, to the same extent as that induced by parental Rev.1
      strain. Thus, these Rev.1 bp26 or omp31 deletion mutants are promising vaccine
      candidates against B. melitensis and B. ovis infections and will be further
      evaluated in sheep.

PMID- 15246619
TI  - Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in
      adults, toddlers and previously uninfected infants.
AB  - A live attenuated human rotavirus (HRV) vaccine, strain RIX4414, was tested
      sequentially in adults, previously infected toddlers, and previously uninfected
      infants. A single dose was given to adults and toddlers and found well tolerated.
      Next, a dose ranging (three different viral concentrations) safety and
      immunogenicity study was conducted in rotavirus IgA antibody negative infants (N=
      192), who received two doses of RIX4414 vaccine or placebo at 2 and 4 months of
      age. No side effects were seen after vaccination. Specifically, administration of
      RIX4414 vaccine was not temporally associated with fever, diarrhea, or increase
      in liver transaminases. Rotavirus IgA seroconversion ranged from 50 to 88% after
      one dose and from 73 to 96% after two doses, depending on vaccine titer. After
      the first dose, on days 7-9 post vaccination, between 38 and 60% of the infants
      shed the vaccine virus, whereas after the second dose only 0 to 13% of the
      vaccinees shed the vaccine virus. It is concluded that RIX4414 strain HRV vaccine
      is virtually non-reactogenic and, at high titer, highly immunogenic in
      susceptible infants.

PMID- 15246620
TI  - Development of an in vitro-based potency assay for anthrax vaccine.
AB  - The potency assay currently used to evaluate consistency of manufacture for the
      anthrax vaccine is contingent upon meeting specified parameters after statistical
      analysis of the percent survival and time to death of vaccinated guinea pigs
      after challenge with spores of a virulent strain of Bacillus anthracis. During
      the development of a new anthrax vaccine based upon recombinant protective
      antigen (rPA) adsorbed to aluminum hydroxide gel (Alhydrogel), we found that the
      serological response of female A/J mice, as measured by a quantitative anti-rPA
      IgG ELISA, may be an effective method to monitor a manufacturer's consistency for
      rPA-based vaccines. An advantage of the proposed in vitro-based potency assay is
      that it will not need stringent biosafety containment measures as required by the
      current guinea pig potency assay.

PMID- 15246621
TI  - Estimating influenza-related hospital admissions in older people from GP
      consultation data.
AB  - This study seeks to determine the association between general practice (GP)
      consultations for influenza-like illness (ILI) and hospital admissions, and to
      estimate the number of excess hospitalisation due to ILI epidemics, for two age
      groups: 51-65 years and >65 years. METHODS: Structural time series models (STSM)
      with stochastic trend and seasonal components were developed. Weekly data from
      Switzerland for 1987 to 1996/1997 were used. Hospital admission rates for
      pneumonia and influenza (P&I) and other respiratory conditions (ORC) were
      regressed against GP consultation rates. Excess hospitalisations were calculated
      as the difference between predicted hospital admissions during influenza
      epidemics and predicted hospital admissions using a baseline GP consultation
      rate. RESULTS: Excess admission rates were substantially higher in the oldest age
      group (51-65 years: P&I 4.42, ORC 2.14; >65 years: P&I 6.30, ORC 4.74 per 10,000
      population per year). The models explained between 43 and 76% of the variation in
      hospital admissions. The seasonal patterns were stable over the 10 years modelled
      and the variances of the trends were small.

PMID- 15246622
TI  - Starch microparticles as an adjuvant in immunisation: effect of route of
      administration on the immune response in mice.
AB  - This paper describes the effects on the development of an immune response by
      changing the route of administration of a new vaccine adjuvant, starch
      microparticles with human serum albumin (HSA) as a model antigen. The model
      vaccine was administered to mice by oral, subcutaneous and intramuscular routes
      in various combinations and both the local secretory immunoglobulin antibody (s
      IgA) and systemic humoral and cellular (delayed-type hypersensitivity assay
      (DTH)) responses were followed. The only immunisation regimens inducing a
      significant s-IgA response were those incorporating oral booster doses. Oral and
      subcutaneous immunisations had similar effects on the Th1/Th2 balance, as
      indicated by the IgG subclass ratios and cytokine analyses. However, significant
      differences between oral and intramuscular immunisations were seen in the IgG
      subclass ratios. The Th2 influence was stronger after oral primary immunisation
      than after intramuscular primary immunisation, while oral boosters elicited a
      comparatively stronger Th1 response than intramuscular boosters. This result was
      also supported by the DTH analyses. Subcutaneous immunisation induced a stronger
      Th2 response than intramuscular immunisation, as indicated by subclass ratio and
      the IgE response. In conclusion, our results show that the profile of an immune
      response depends on the route of administration, which should be considered when
      developing new vaccines or new routes of administration.

PMID- 15246623
TI  - Identification of adjuvants that enhance the therapeutic antibody response to
      host IgE.
AB  - In the development of a novel vaccine against atopic allergies, we have screened
      for adjuvants that enhance the therapeutic antibody response against self
      immunoglobulin E (IgE). The response against self IgE is induced by
      administration of a vaccine antigen, which contains both self and non-self IgE
      regions, together with an adjuvant. We evaluated five commonly used adjuvants;
      Freund's, aluminium hydroxide, ISCOMs, Montanide ISA 51 and Montanide ISA 720,
      and found that the mineral oil-based adjuvants; Montanide ISA 51 and Freund's
      induced at least 5-10-fold higher anti-self IgE titers than any of the other
      candidates. However, with one exception, Alum, the immune responses against the
      carrier, i.e. the non-self regions, were similar for all adjuvants, indicating
      that the ability to induce responses against self and non-self antigens differ
      among adjuvants. The responses against non-self IgE were more than 50-fold higher
      than antibody responses against self IgE in both the Freund's and Montanide 51
      administered animals, indicating that the response against self molecules is
      markedly inhibited by tolerance-inducing mechanisms. Co-administration of
      Montanide ISA 51 with immuno-stimulatory substances from bacteria;
      muramyldipeptide (MDP), monophosphoryl-lipid A (MPL) or a formyl-methionine
      containing tripeptide (fMLP), did not elevate the anti-self IgE response. Hence,
      adjuvants based on pure mineral oil without additional immuno-stimulatory
      substances appear to be the best adjuvant candidates in therapeutic vaccines
      aimed at regulating the in vivo levels of self-proteins.

PMID- 15246624
TI  - CpG oligonucleotides improve the protective immune response induced by the
      anthrax vaccination of rhesus macaques.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as
      immune adjuvants, improving the immune response elicited by co-administered
      vaccines. Combining CpG ODN with anthrax vaccine adsorbed (AVA, the licensed
      human vaccine) increased the speed, magnitude and avidity of the resultant anti
      anthrax response. The protective activity of these Abs was established by passive
      transfer to anthrax-challenged mice. The ability of CpG ODN to accelerate and
      magnify the immune response to AVA suggests this strategy may contribute to the
      development of prophylactic and therapeutic vaccines against biothreat pathogens.

PMID- 15246625
TI  - Vaccination with formalin-inactivated influenza vaccine protects mice against
      lethal influenza Streptococcus pyogenes superinfection.
AB  - Intranasal infection with non-lethal influenza A virus (IAV) followed by
      infection with group A streptococci (GAS) induces invasive, lethal GAS
      infections, including necrotizing fasciitis, in mice. We demonstrate that
      subcutaneous immunization of formalin-inactivated IAV vaccine or intranasal
      immunization of IAV vaccine and cholera toxin protected more than 75% of mice
      from death by lethal IAV-GAS superinfection. The increased survival rate
      correlates with increase in IAV neutralizing activity and the levels of serum
      anti-IAV IgG. Moreover, elimination of IAV from the lungs of vaccinated mice led
      to depletion of GAS associated with alveolar epithelial cells. These findings
      suggest that formalin-inactivated IAV vaccine may be useful for prevention of
      secondary bacterial infections following prior IAV exposure.

PMID- 15246626
TI  - Local delivery of recombinant vaccinia virus expressing secondary lymphoid
      chemokine (SLC) results in a CD4 T-cell dependent antitumor response.
AB  - Secondary lymphoid chemokine (SLC) attracts mature dendritic cells (DCs) and
      naive T cells. Co-localization of these cells within local tumor environments may
      enhance the induction of tumor-specific T cells. However, the presence of danger
      signals or other DC maturation signals are required to optimize T-cell priming.
      We hypothesized that expression of SLC in vaccinia virus would provide local
      chemokine delivery and adjuvant factors. A recombinant vaccinia virus expressing
      murine SLC (rVmSLC) was constructed and characterized. SLC expression was
      confirmed by Western blot analysis and functional activity was determined by in
      vitro chemotaxis assay. Supernatants from rVmSLC-infected cells attracted CD4 T
      cells, and also induced the migration of CD8 T cells and DCs. Although poxviruses
      are known to express several chemokine-binding proteins, systemic injection of
      rVmSLC was well tolerated in mice up to a dose of 1 x 10(7) pfu and did not
      significantly alter vaccinia-specific T-cell immunity. Local injection of rVmSLC
      into established tumors derived from the murine colon cancer line, CT26, resulted
      in enhanced infiltration of CD4 T cells, which correlated with inhibition of
      tumor growth. The central role of CD4 T cells was further demonstrated by loss of
      anti-tumor activity in CD4 T-cell depleted mice. Intratumoral delivery of SLC
      using a poxviral vaccine extends the use of SLC in anti-tumor therapies and may
      present an effective alternative for improving the immunotherapy of cancer alone
      or in combination with other anti-tumor agents for clinical therapy.

PMID- 15246628
TI  - Novel biocompatible anionic polymeric microspheres for the delivery of the HIV-1
      Tat protein for vaccine application.
AB  - Two novel classes of biocompatible core-shell anionic microspheres, composed of
      an inner hard insoluble core, either made of poly(styrene) (PS) or poly(methyl
      methacrylate) (PMMA), and a soft outer tentacular shell made of long soluble
      negatively charged arms derived from the steric stabilizer, hemisuccinated
      poly(vinyl alcohol) or Eudragit L100/55, respectively, were prepared by
      dispersion polymerization and characterized. Five types of these novel
      microspheres, two made of poly(styrene) and hemisuccinated poly(vinyl alcohol)
      (A4 and A7), and three made of poly(methyl methacrylate) and Eudragit L100/55
      (1D, 1E, H1D), differing for chemical composition, size, and surface charge
      density were analyzed for the delivery of the HIV-1 Tat protein for vaccine
      applications. All microspheres reversibly adsorbed the native biologically active
      HIV-1 Tat protein preventing Tat from oxidation and maintaining its biological
      activity, therefore increasing the shelf-life of the Tat protein vaccine. The
      microspheres efficiently delivered Tat intracellularly, and were not toxic in
      vitro nor in mice, even after multiple administrations. These results indicate
      that these novel microparticles are safe and represent a promising delivery
      system for vaccination with Tat, as well as for other subunit vaccines,
      particularly when a native protein conformation is required.

PMID- 15246627
TI  - A phase II trial comparing five dose levels of BEC2 anti-idiotypic monoclonal
      antibody vaccine that mimics GD3 ganglioside.
AB  - In previous studies, we showed that immunization with 2.5 mg of BEC2, an anti
      idiotypic MAb that mimics GD3 ganglioside, can induce antibodies against GD3 in
      approximately 25% of patients. In this trial, 50 melanoma patients at high risk
      for recurrence were randomly assigned to one of the five BEC2 dose levels (2.5
      microg-10mg) to determine if lower or higher BEC2 doses are more immunogenic. We
      also tested whether prolonged booster immunizations can enhance the anti-GD3
      antibody response. All patients developed detectable IgG against BEC2 except for
      one patient at the lowest BEC2 dose level. Six patients developed detectable
      antibody responses to GD3, all of them at the lower three dose levels of BEC2. We
      conclude that high doses of BEC2 are not necessary to induce anti-GD3 antibody
      responses and that lower doses may be more immunogenic than the 2.5 mg dose used
      in previous BEC2 trials. Prolonged booster immunizations did not induce or
      maintain antibody responses.

PMID- 15246629
TI  - Effect of chemical adjuvants on DNA vaccination.
AB  - DNA vaccination is useful for generating immune responses, particularly the cell
      mediated immune response, in a wide variety of species. However, DNA vaccination
      generally induces only relatively weak responses; hence, various approaches have
      been developed recently in order to improve its efficacy or immunopotency. The
      use of a chemical adjuvant is one of them. Previously we have shown that
      Bupivacaine or Marcaine can modulate immune responses induced by DNA vaccines
      [Proc. Natl. Acad. Sci. 90 (1993) 4156]. Following that lead, we have recently
      tested several additional chemicals for their usefulness as adjuvants in DNA
      inoculation. Of a total of five chemicals tested, levamisole exhibited strongest
      Th1 stimulatory activity whereas Tween 80 showed weakest Th1 activity, as
      determined by IgG2a production, and saline formulation induced weak T cell
      proliferation and DTH, in animals inoculated with a DNA construct expressing the
      foot-mouth disease viral capsule protein VP1. Furthermore, co-inoculation of
      levamisole increased the production of IFN-gamma by more than 100-fold as
      compared to that by DNA inoculation formulated in saline. In contrast, a
      previously reported chemical adjuvant, bupivacaine, stimulated only modest levels
      of overall antibody production, with relatively low level of Ig2a. These results
      demonstrate the usefulness of various chemicals, particularly levamisole, for
      modulating the outcome of DNA vaccination, in both the intensity of the immune
      response and the polarity of such response (toward Th1).

PMID- 15246630
TI  - Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like
      particle vaccine.
AB  - A post hoc analysis was performed using combined data from two Phase I
      tolerability/immunogenicity studies of monovalent human papillomavirus type 11
      (HPV11) or HPV16 L1 virus-like particle (VLP) vaccines. The goal was to determine
      if the HPV16 L1 VLP vaccine protected against HPV16 infection. Vaccine or placebo
      was given at 0, 2 and 6 months. HPV16 infection was defined by positive
      polymerase chain reaction (PCR) results following vaccination. The incidence of
      HPV infection was observed to be 0 cases per 100 person-years at risk in the
      vaccine group, and 5 cases per 100 person-years at risk in the control group.
      These results support the institution of larger efficacy trials for HPV L1 VLP
      vaccines.

PMID- 15246631
TI  - Dose-ranging studies of the safety and immunogenicity of human papillomavirus
      Type 11 and Type 16 virus-like particle candidate vaccines in young healthy
      women.
AB  - Two candidate vaccines to prevent infection with human papillomavirus (HPV) Types
      11 and 16 were studied in similar double-blind, placebo-controlled, dose
      escalation trials. L1 virus-like particle (VLP) vaccines were made from
      recombinant L1 capsid protein of HPV11 or HPV16. Participants received 10, 20,
      50, or 100 microg of HPV11 L1 VLPs, 10, 40, or 80 microg of HPV16 L1 VLPs, or
      placebo at Months 0, 2, and 6. Serum geometric mean antibody levels at Month 7
      were 258, 644, 647, and 1112 milli-Merck units (mMU)/ml for the 10, 20, 50, and
      100 microg doses of the HPV11 L1 VLP vaccine, respectively, and 479, 808, and 732
      mMU/ml for the 10, 40, and 80 microg doses of the HPV16 L1 VLP vaccine,
      respectively. Antibody to HPV11 and 16 was still present at Month 36 in 96.8 and
      93.5% of vaccinees, respectively. Both vaccines were well tolerated and were
      associated with only mild to moderate injection-site reactions.

PMID- 15246632
TI  - Pertussis vaccination strategies for neonates--an exploratory cost-effectiveness
      analysis.
AB  - Hospitalisation and death from pertussis in highly immunised populations largely
      occurs before the first vaccination at 2 months. A Markov model was constructed
      to estimate the costs and health consequences of three strategies to reduce
      pertussis over the first 6 months of an infant's life. Earlier vaccination (at
      either birth or 1 month in addition to current practice) or vaccination of the
      parents soon after birth was compared with the current practice of vaccination at
      2, 4 and 6 months. The model was populated using data on the incidence and costs
      from Australia. Disability-adjusted life-years (DALYs) were used as the primary
      outcome measure. The cost to the Australian public health system was chosen as
      the economic perspective, and Monte-Carlo simulations were used to accommodate
      uncertainties in the variables. Vaccination at birth was estimated to cost (S.D.)
      an additional A$33.21 (A$1.60) per infant and to reduce cases, deaths and DALYs
      by 45%. Vaccination at 1 month was estimated to cost an additional A$43.24
      (A$8.98) per infant and to reduce morbidity by approximately 25%. Parental
      vaccination at birth was the most expensive alternative, costing an additional
      A$73.38 (A$4.98) per infant and reducing pertussis morbidity by 38%. The costs
      per DALY averted were A$330,175 (A$15,461) A$735,994 (A$147,679) and A$787,504
      (A$48,075) for the birth, 1 month and parental vaccination strategies,
      respectively. Changing the estimated factor by which hospitalisations and deaths
      are under-reported, and the efficacy of early vaccination, had large effects on
      results. Parental vaccination at birth was most cost-effective where protection
      persisted for subsequent children. The birth vaccination strategy appears to
      offer the greatest potential benefit for one-child families, but the efficacy at
      birth (and 1 month) needs to be established.

PMID- 15246633
TI  - Appearances can deceive: even brave hearts can fail.

PMID- 15246634
TI  - High-dose dobutamine stress cardiac magnetic resonance imaging--has its time
      come?

PMID- 15246635
TI  - Atrial amyloidosis and atrial fibrillation: a gender-dependent "arrhythmogenic
      substrate"?

PMID- 15246636
TI  - Role and importance of biochemical markers in clinical cardiology.
AB  - This paper reviews the current contribution of the biochemical marker
      determination to clinical cardiology and discusses some important developments in
      this field. Biochemical markers play a pivotal role in the diagnosis and
      management of patients with acute coronary syndrome (ACS), as witnessed by the
      incorporation of cardiac troponins into new international guidelines for patients
      with ACS and in the re-definition of myocardial infarction. Despite the success
      of cardiac troponins, there is still a need for the development of early markers
      that can reliably rule out ACS from the emergency room at presentation and also
      detect myocardial ischaemia in the absence of irreversible myocyte injury. Under
      investigation are two classes of indicators: markers of early injury/ischaemia
      and markers of inflammation and coronary plaque instability and disruption.
      Finally, with the characterisation of the cardiac natriuretic peptides,
      Laboratory Medicine is also assuming a role in the assessment of cardiac
      function.

PMID- 15246637
TI  - Atherothrombosis: a widespread disease with unpredictable and life-threatening
      consequences.
AB  - Atherothrombosis, characterised by atherosclerotic lesion disruption with
      superimposed thrombus formation, is the major cause of acute coronary syndromes
      (ACS) and cardiovascular death. It is the leading cause of mortality in the
      industrialised world. Atherosclerosis is a diffuse process that starts early in
      childhood and progresses asymptomatically through adult life. Later in life, it
      is clinically manifested as coronary artery disease, stroke, transient ischaemic
      attack, and peripheral arterial disease. From the clinical point of view, we
      should envision this disease as a single pathologic entity that affects different
      vascular territories. Available antithrombotic therapy is very safe and efficient
      but the morbidity and mortality due to atherothrombosis is still unacceptably
      high. Recent evidence suggests that inhibition of tissue factor or elements in
      the tissue factor pathway (i.e., factors VIIa and Xa, or thrombin) has the
      potential to further improve outcomes in atherothrombosis. Here, we will review
      the most important concepts and advances in the pathogenesis, prevention, and
      antithrombotic treatment of this widespread disease.

PMID- 15246638
TI  - Percutaneous coronary interventions in Europe 1992-2001.
AB  - AIMS: The purpose of this registry is to collect data on trends in interventional
      cardiology within Europe. Special interest focuses on relative increases and
      ratios in newer re-vascularisation approaches and its distribution in different
      regions in Europe. We report the data of the year 2001 and give an overview of
      the development of coronary interventions since 1992, when the first data
      collection was performed. METHODS AND RESULTS: Questionnaires were distributed to
      delegates of the individual national societies of cardiology represented in the
      European Society of Cardiology. These were completed by the local institutions
      and operators and showed that 1,806,238 angiograms and 617,176 percutaneous
      transluminal coronary angioplasties (PTCAs) were performed in 2001. This is an
      increase of 10% and 17%, respectively, compared with the year 2000. The
      population-adjusted PTCA rate rose from nearly 800 procedures per 10(6)
      inhabitants in the year 2000 to approximately 990 procedures per 10(6)
      inhabitants in 2001. Coronary stenting increased by 25% to about 488,900 stents
      implanted in 2001. Complication rates remained unchanged, and the need for
      emergency coronary artery bypass grafting is still at 0.2% per percutaneous
      intervention. CONCLUSION: Interventional cardiology in Europe is still expanding,
      mainly due to rapid growth in countries with lower socio-economical levels. Most
      central European countries reported only minor increases in procedures performed.
      Coronary stenting remains the only noteworthy adjunctive strategy to balloon
      angioplasty.

PMID- 15246639
TI  - Differences between patients with a preserved and a depressed left ventricular
      function: a report from the EuroHeart Failure Survey.
AB  - AIMS: Due to a lack of clinical trials, scientific evidence regarding the
      management of patients with chronic heart failure and preserved left ventricular
      function (PLVF) is scarce. The EuroHeart Failure Survey provided information on
      the characteristics, treatment and outcomes of patients with PLVF as compared to
      patients with a left ventricular systolic dysfunction (LVSD). METHODS AND
      RESULTS: We performed a secondary analysis using data from the EuroHeart Failure
      Survey, only including patients with a measurement of LV function (n = 6806). We
      selected two groups: patients with LVSD (54%) and patients with a PLVF (46%).
      Patients with a PLVF were, on average, 4 years older and more often women (55%
      vs. 29%, respectively, p < 0.001) as compared to LVSD patients, and were more
      likely to have hypertension (59% vs. 50%, p < 0.001) and atrial fibrillation (25%
      vs. 23%, p = 0.01). PLVF patients received less cardiovascular medication
      compared to PLVF patients, with the exception of calcium antagonists.
      Multivariate analysis revealed that LVSD was an independent predictor for
      mortality, while no differences in treatment effect on mortality between the two
      groups was observed. A sensitivity analysis, using different thresholds to
      separate patients with and without LVSD revealed comparable findings.
      CONCLUSIONS: In the EuroHeart Failure Survey, a high percentage of heart failure
      patients had PLVF. Although major clinical differences were seen between the
      groups, morbidity and mortality was high in both groups.

PMID- 15246640
TI  - N-methylethanolamine attenuates cardiac fibrosis and improves diastolic function:
      inhibition of phospholipase D as a possible mechanism.
AB  - AIM: Ventricular fibrosis is promoted by many effectors that chronically activate
      phospholipase D (PLD), and induces cardiac dysfunction and heart failure in
      cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised
      that an administration of an analogue of ethanolamine, N-methylethanolamine
      (MEA), decreases PLD activity through a negative feedback mechanism, suppresses
      collagen accumulation, and thus prevents organ dysfunction. METHODS AND RESULTS:
      In human fibroblasts 1-butanol inhibited collagen synthesis and enhanced
      collagenase production, but iso-butanol did not. These indicate crucial roles of
      PLD in collagen synthesis and degradation. In fibroblasts, MEA dose-dependently
      decreased PLD activity, inhibited collagen synthesis and enhanced collagenase
      production. In a hypertensive heart failure model using Dahl-Iwai salt-sensitive
      rats, PLD activity increased with progressive ventricular fibrosis, leading to
      myocardial stiffening and overt heart failure. Long-term administration of MEA
      did not significantly decrease blood pressure, however, but decreased PLD
      activity and collagen content with inhibited gene expression of collagens,
      leading to the prevention of myocardial stiffening and haemodynamic
      deterioration. MEA also attenuated ventricular hypertrophy, another detrimental
      structural alteration. CONCLUSION: MEA may exert therapeutic effects on cardiac
      disorders due to ventricular fibrosis through suppression of PLD activity and
      modulation of the fibrosis pathway even without relief from mechanical stress.

PMID- 15246641
TI  - Safety and feasibility of high-dose dobutamine-atropine stress cardiovascular
      magnetic resonance for diagnosis of myocardial ischaemia: experience in 1000
      consecutive cases.
AB  - AIMS: To determine the safety of high-dose dobutamine-atropine stress
      cardiovascular magnetic resonance (stress-CMR), which recently emerged as a
      highly accurate modality for diagnosis of inducible myocardial ischaemia. METHOD
      AND RESULTS: From 1997 to 2002, 1000 consecutive stress-CMR examinations were
      performed. Images were acquired at rest and during a high-dose dobutamine
      atropine protocol in 3 short-axis, a 4- and a 2-chamber view. Stress testing was
      discontinued when > or =85% of age-predicted heart rate was reached, on patient
      request, maximum pharmacologic infusion, or when new or worsening wall motion
      abnormalities, severe angina, dyspnoea, increase or decrease in blood pressure,
      or severe arrhythmias occurred. Stress-CMR was successfully performed in all but
      four patients (0.4%; insufficient ECG-triggering). Target heart rate was not
      reached in 95 cases (9.5%), due to maximum pharmacologic infusion in submaximal
      negative examinations in 21 cases (2.1%), and limiting side effects in 74 (7.4%).
      Side effects included one case (0.1%) of sustained and four cases (0.4%) of non
      sustained ventricular tachycardia, 16 cases (1.6%) of atrial fibrillation, and
      two cases (0.2%) of transient second degree AV block. CONCLUSION: The safety
      profile of stress-CMR is similar to other methodologies using dobutamine
      infusions. Patients must be closely monitored, and resuscitation equipment and
      trained personnel must be available.

PMID- 15246642
TI  - Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial
      fibrillation.
AB  - AIM: The spectrum of histological alterations, namely atrial amyloidosis, in the
      right and left atria of patients with chronic persistent atrial fibrillation (AF)
      and rheumatic heart disease is not completely known. METHODS AND RESULTS: One
      hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from
      72 patients with rheumatic valve disease and chronic AF undergoing cardiac
      surgery for valve replacement or repair and AF treatment were histologically
      evaluated for the presence of amyloid deposits. One hundred and four specimens of
      left and right auricles from 52 patients in sinus rhythm with severe chronic
      heart failure undergoing heart transplant were also analyzed (controls). Amyloid
      was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%)
      controls. Amyloid was related to the presence and duration of AF, was more
      frequently found in left atrial samples and was independent of age. On stepwise
      logistic regression analysis, AF duration and female gender were independently
      related to amyloid deposition. CONCLUSIONS: Patients with long-standing AF and
      rheumatic heart disease have a very high prevalence of atrial amyloidosis.
      Amyloid deposition is more frequent in left than in right atrial appendage and
      correlates with AF duration and female gender. Amyloid deposition could
      constitute an additional histological feature in the structural remodeling of
      atria during long-standing AF, at least in rheumatic valve disease. Persistence
      of AF might play a pivotal role in promoting amyloid deposition.

PMID- 15246643
TI  - Autonomic nervous system and paroxysmal atrial fibrillation: a study based on the
      analysis of RR interval changes before, during and after paroxysmal atrial
      fibrillation.
AB  - AIMS: To evaluate the presence of an abnormal autonomic modulation before, during
      and immediately after paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS:
      We analysed Holter recordings of 65 patients with 110 PAF episodes lasting more
      then 30 s. Mean RR interval, co-efficient of variation and short-term heart rate
      variability were measured before, during and after PAF episodes. We observed a
      significant correlation between the coupling interval and both the cycle length
      measured from 30 min up to few cycles before PAF onset, and ventricular response.
      When comparing the heart rate variability (HRV) before and after PAF we observed
      a significant reduction of the low frequency/high frequency components (LF/HF)
      ratio (from 6.2+/-7.4 to 3.2+/-4.1). A short-long-short cycle sequence was
      detectable in 37 PAF onsets associated with a greater incidence of atrial ectopic
      beats and a greater LF component (62+/-25 vs. 53+/-27 normalised units) in
      comparison to the remaining episodes. When onsets were divided for a LF/HF ratio
      cut-off value of > or = 2 to separate episodes with a predominant sympathetic, as
      opposed to those with a prevailing vagal (LF/HF<2) modulation, we observed
      opposite changes (from 9.1+/-7.8 to 4+/-3.7 and from 0.8+/-0.5 to 2+/-3.6,
      respectively) consistent with a recovery of a more physiological sympatho-vagal
      balance immediately after recovery of sinus rhythm. No changes in co-efficient of
      variation of ventricular response were detectable before PAF termination.
      CONCLUSIONS: A predominant sympathetic modulation characterises the majority of
      PAF onsets whereas a vagal predominance was detectable in about 30% of episodes.
      These patterns are no longer detectable after recovery of sinus rhythm.

PMID- 15246644
TI  - Sub-threshold stimulation in variants of atrioventricular nodal re-entrant
      tachycardia: electrophysiological effects and impact for guidance of slow pathway
      ablation.
AB  - AIM: Sub-threshold stimulation (STS) applied during atrioventricular nodal re
      entrant tachycardia (AVNRT) of the common (slow-fast) type has been shown to
      effectively characterise target sites suitable for slow pathway (SP) ablation but
      has not been investigated in the setting of fast-slow and slow-slow variants.
      METHODS AND RESULTS: Seventeen consecutive patients (52+/-16 years, 12 female)
      with sustained uncommon type AVNRT (fast-slow: n = 13, slow-slow: n = 4) were
      investigated. Mapping of the SP was started postero-septally close to the
      coronary sinus ostium and continued toward mid-septal sites, if required. Target
      sites for STS were selected according to established criteria including the
      recording of the earliest retrograde atrial activation during AVNRT. Long
      duration (5 s) constant current STS during AVNRT variants was performed in a
      stepwise manner (max 5 mA) at each site eligible for SP ablation until
      termination or capture occurred. Radiofrequency current (RFC) was delivered
      following successful STS termination of tachycardia (65 degrees C, 60 s) and
      exclusion of catheter dislodgement. Uncommon AVNRT with a mean cycle length of
      405+/-70 ms was induced without spontaneous termination in all patients.
      Interruption of AVNRT variants due to selective STS-induced block of the
      retrograde (n = 12) or anterograde (n =2) SP occurred without capture in 14/17
      (82%) patients. This was exclusively observed at sites with successful subsequent
      RFC application. AVNRT was rendered non-inducible in all patients after a median
      of 1 (1-11) RFC pulses without complications. CONCLUSIONS: Uncommon AVNRT can be
      interrupted by STS delivered at subsequently successful target sites for SP
      ablation in most patients (82%). The high positive and negative concordance
      between the effects of STS and following RFC application indicates that STS
      mapping is also useful in the setting of AVNRT variants.

PMID- 15246645
TI  - Use of implantable loop recorders in the diagnosis and management of syncope.
AB  - BACKGROUND: Syncope is a common, disabling symptom. The most useful data for
      diagnosing and managing syncope is the recording of physical parameters such as
      the ECG and blood pressure during a spontaneous event. Implantable loop recorders
      (ILR) provide an opportunity to record ECG data from a spontaneous event. The
      purpose of the Eastbourne Syncope Assessment Study (EaSyAS) was to investigate
      the impact of ILRs on an unselected population of syncopal patients presenting
      acutely to our institution. METHODS: All patients presenting acutely with
      recurrent, unexplained syncope over a 16-month period, were randomised after a
      basic clinical workup to receive the Reveal Plus ILR or conventional
      investigation. All patients were followed up for at least 6 months (mean 276+/
      134 days) following randomisation. The primary outcome measure was time to ECG
      diagnosis. RESULTS: Four hundred twenty-one patients presented, 201 were
      eligible, median age 74 years (interquartile range 61-81 years), 54% female, with
      a median of three previous syncopes (IQ range 2-6). Thirty-three percent of ILR
      patients and 4% of conventional patients had an ECG diagnosis (hazard ratio 8.93,
      95% CI 3.17-25.2, p < or = 0.0001). Introduction of ECG-directed therapy was
      quicker for ILR patients (hazard ratio 7.9, 95% CI 2.8-22.3, p < 0.0001). ILR
      patients had fewer post-randomisation investigations and fewer hospital days,
      resulting in a saving of costs, 406 UK pounds versus 1210 UK pounds (mean
      difference 809 UK pounds, 95% CI 123-2730 UK pounds). There was no difference in
      the number of subsequent syncopal episodes, mortality, or quality of life.
      CONCLUSIONS: LR significantly increased the rate of diagnosis in an unselected
      Western population with recurrent syncope. There was a significant decrease in
      the rates of hospitalisation and investigation in patients receiving an ILR.

PMID- 15246646
TI  - Decline in ventricular function and clinical condition after Mustard repair for
      transposition of the great arteries (a prospective study of 22-29 years).
AB  - BACKGROUND: Great concern exists about the ability of the anatomic right
      ventricle to sustain the systemic circulation in patients with transposition of
      the great arteries who have undergone a Mustard procedure. A prospective study
      was made to examine long-term survival, clinical outcome, and right ventricular
      function 25 years after surgery. METHODS: Ninety-one consecutive patients
      underwent the Mustard procedure between 1973 and 1980. After 14 years and again
      after 25 years (range 22-29 years), patients were studied with ECG,
      echocardiography, exercise testing, and Holter monitoring. RESULTS: The
      cumulative survival and event-free survival were 77% and 36%, respectively, after
      25 years. Reoperation was necessary in 46%. No major loss of sinus rhythm was
      found. While all patients had good right ventricular function 14 years after
      repair, 61% of patients showed moderate-to-severe dysfunction after 25 years,
      when studied by echocardiography. Furthermore, the QRS complex widened and
      exercise capacity decreased. CONCLUSION: The anatomic right ventricle appears to
      be unable to sustain the systemic circulation at long-term follow-up and the
      clinical condition of patients late after Mustard repair is declining. We can
      expect more deaths or need for heart transplantation in the next decade.

PMID- 15246647
TI  - Leader RNA of Rinderpest virus binds specifically with cellular La protein: a
      possible role in virus replication.
AB  - Rinderpest virus (RPV) is an important member of the Morbillivirus genus in the
      family Paramyxoviridae and employs a similar strategy for transcription and
      replication of its genome as that of other negative sense RNA viruses. Cellular
      proteins have earlier been shown to stimulate viral RNA synthesis by isolated
      nucleocapsids from purified virus or from virus-infected cells. In the present
      work, we show that plus sense leader RNA of RPV, transcribed from 3' end of
      genomic RNA, specifically interacts with cellular La protein employing gel
      mobility shift assay as well as UV cross-linking of leader RNA with La protein.
      The leader RNA synthesized in virus-infected cells was shown to interact with La
      protein by immunoprecipitation of leader RNA bound to La protein and detecting
      the leader RNA in the immunoprecipitate by Northern hybridization with labeled
      antisense leader RNA. Employing a minireplicon system, we demonstrate that
      transiently expressed La protein enhances the replication/transcription of the
      RPV minigenome in cells. Sub-cellular immunolocalization shows that La protein is
      redistributed from nucleus to the cytoplasm upon infection. Our results strongly
      suggest that La protein may be involved in regulation of Rinderpest virus
      replication.

PMID- 15246648
TI  - The Heliothis armigera single nucleocapsid nucleopolyhedrovirus envelope protein
      P74 is required for infection of the host midgut.
AB  - In order to study the function of the envelope protein P74 of Heliothis armigera
      single nucleocapsid nucleopolyhedrovirus (HaSNPV), a p74-null recombinant
      baculovirus, rHa-gfdeltap74, was constructed by inserting gfp driven by the
      polyhedrin promoter into the p74 locus of HaSNPV genome. The resulting p74
      inactivation occlusion-derived viruses (ODV) failed to infect its natural host
      larvae per os. However, its inability of oral infectivity was rescued using the
      purified P74 protein expressed by Bac-to-Bac system in Hz-AM1 cells. Feeding the
      purified P74 protein along with the p74 deletion mutant virus rHa-gfpdeltap74 to
      H. armigera larvae resulted in the rescue of oral infectivity in a dose dependent
      manner. The P74 protein was expressed in-frame with GFP to create a P74-GFP
      chimera for studying the localization of P74, the GFP portion of the chimera
      facilitating the visualization of the trafficking of P74 in cells. The P74-GFP
      chimeric proteins localized in the intranuclear ring zone and accumulated into
      microvesicles. In addition, the specific and saturable binding of P74 protein to
      its host brush border membrane vesicles (BBMVs) was involved in the invasion of
      virus. Further investigations (pull-down assay) showed that an about 30 kDa
      protein in the BBMVs was involved in the specific binding. These results
      demonstrated that the P74 protein is essential for oral infectivity of ODV and
      plays a role in midgut attachment and fusion.

PMID- 15246649
TI  - Susceptibility of peritoneal macrophages to infection by Theiler's virus.
AB  - Theiler's murine encephalomyelitis virus (TMEV) strains fall into two groups:
      high-neurovirulence GDVII virus results in rapidly fatal encephalitis, while low
      neurovirulence BeAn and DA viruses produce persistent central nervous system
      (CNS) infection and inflammatory demyelinating disease. Because macrophages
      (Mphis) are key components in BeAn virus-induced demyelinating disease, we
      examined the susceptibility of primary peritoneal macrophages (pMphis) to BeAn
      infection in vitro. Freshly isolated, thioglycollate-elicited pMphis were
      resistant to BeAn virus infection even at high multiplicity of infection. In
      contrast, after incubation of thioglycollate-elicited pMphis at 37 degrees C for
      4 days before infection, approximately half of the cells expressed virus
      antigen(s) and contained nicked DNA indicative of apoptosis. However, BeAn virus
      RNA replication and virus yields were highly restricted. Interestingly, about one
      third of the cells were apoptotic but negative for virus RNA and antigen(s).
      Tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) were
      elevated in BeAn-infected pMphi cultures suggesting that bystander killing may be
      responsible for the apoptosis seen in BeAn virus antigen-negative cells. These
      data show for the first time that pMphis are susceptible to BeAn virus infection,
      although the infection is highly restricted and most of these cells undergo BeAn
      induced apoptosis.

PMID- 15246650
TI  - Detection of RNA in purified cytomegalovirus virions.
AB  - Five viral RNA transcripts have recently been detected in purified virions of
      human cytomegalovirus (HCMV) strain AD169, a well-characterized member of the
      family Herpesviridae [Science 288 (2000) 2373]. While the function of these
      transcripts and/or the proteins they encode remains to be elucidated, it is not
      known whether these transcripts are unique to strain AD169 or are present in
      other HCMV strains. The objective of this study was to determine if these RNAs
      are present in other HCMV laboratory strains (Towne and Davis), and a low passage
      clinical isolate (CL203). These strains of CMV were purified by sequential
      ultracentrifugation through 20% D-sorbitol and glycerol-potassium tartarate
      gradients and the morphology and infectivity of the virions confirmed by electron
      microscopy and inoculation into cell culture. When RNA extracted from the
      purified virions was amplified by reverse transcriptase-polymerase chain reaction
      (RT-PCR) the UL 21.5 and TRL/IRL 2-5 transcripts were detected in virions of HCMV
      strains AD169, Davis, Towne and CL203. The presence of the UL 21.5 and TRL/IRL 2
      5 RNA transcripts in all strains tested demonstrates that the packaged
      transcripts occurs in all strains of HCMV suggesting that they may have a
      relevant role in the biology of this virus.

PMID- 15246651
TI  - Maporal virus, a hantavirus associated with the fulvous pygmy rice rat
      (Oligoryzomys fulvescens) in western Venezuela.
AB  - Oryzomine rodents in the southeastern United States, Panama, and southern South
      America are natural hosts of 6 of the 13 viruses known to cause hantavirus
      pulmonary syndrome. The purpose of this study was to extend our knowledge of the
      geographical distribution and genetic diversity of the hantaviruses associated
      with oryzomine rodents in South America. An infectious hantavirus was isolated
      from two fulvous pygmy rice rats captured in western Venezuela. Analyses of
      complete nucleocapsid protein and glycoprotein precursor sequences indicated that
      the isolates are strains of a novel hantavirus (proposed name "Maporal") which is
      phylogenetically most closely related to the viruses known to cause hantavirus
      pulmonary syndrome in southern South America.

PMID- 15246652
TI  - HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in
      vitro and in vivo: implications for AIDS-associated vasculopathy.
AB  - HIV-1-infected patients exhibit severe damages of the aortic endothelium, develop
      angioproliferative lesions such as Kaposi's sarcoma (KS), and have an increased
      risk of cardiovascular diseases and atherosclerosis. An increased adhesion of
      leukocytes to the endothelium is a common pathogenic parameter of AIDS-associated
      vascular diseases. Here we show that the HIV-1 Tat protein, a regulatory protein
      of HIV-1 released by infected cells, and TNF-alpha, a cytokine increased in sera
      and tissues of HIV-1-infected patients, activate synergistically the adhesion of
      leukocytes to endothelial cells both in vitro and in vivo. This effect is
      selectively mediated by HIV-1 Tat, since HIV-1 Nef, another HIV-1 regulatory
      protein, and the HIV-1 envelope protein gp41, had no effect. In vitro adhesion
      assays with PBMC and quantitative cell type analysis of adherent cells by FACS
      demonstrated that HIV-1 Tat selectively activates the adhesion of T-cells and
      monocytes but not of B-cells. Intravital microscopic studies in mice confirmed
      the synergistic activity of HIV-1 Tat and TNF-alpha on leukocyte adhesion to the
      endothelium in vivo. These data indicate that HIV-1 Tat in cooperation with TNF
      alpha may contribute to the vascular damage and cardiovascular diseases observed
      in AIDS patients but also to the prominent extravasation of T-cells and monocytes
      which is a key process in the formation and progression of KS lesions.

PMID- 15246653
TI  - Generation of an infectious cDNA clone of an FMDV strain isolated from swine.
AB  - A full-length cDNA clone of a foot-and-mouth disease virus (FMDV) isolated from
      swine was assembled in, the plasmid vector pBluescript II SK+ downstream of a T7
      promoter. RNA synthesized in vitro using T7 polymerase lead to the production of
      infectious particles upon transfection of BHK-21 cells, as shown by cytopathic
      effects. The rescued virus was also found to be highly pathogenic for mice by
      intradermal injection producing a fatal disease indistinguishable from that of
      wild-type virus. The availability of this cDNA clone will allow examination of
      the molecular mechanisms behind FMDV virulence and attenuation, which might in
      turn allow the production of second-generation, genetically engineered FMDV
      vaccines.

PMID- 15246654
TI  - Molecular characterization of PL97-1, the first Korean isolate of the porcine
      reproductive and respiratory syndrome virus.
AB  - We determined the complete nucleotide and predicted amino acid sequence of the
      genomic RNA of PL97-1, the first Korean strain of porcine reproductive and
      respiratory syndrome virus (PRRSV), which was isolated from the serum of an
      infected pig in 1997. We found that the 15411-nucleotide genome of PL97-1
      consisted of a 189-nucleotide 5' noncoding region (NCR), a 15071-nucleotide
      protein-coding region, and a 151-nucleotide 3'NCR, followed by a poly (A) tail.
      The 5'-end of PL97-1 began with 1ATG ACG TAT AGG12. Comparison of the PL97-1
      genome with the 11 fully sequenced PRRSV genomes currently available revealed
      sequence divergence ranging from 0.3% (the VR-2332-derived vaccine MLV
      RespPRRS/Repro strain) to 38% (the Dutch Lelystad strain). To better understand
      the genetic relationships between these different strains, phylogenetic analyses
      were performed on the full-length PRRSV genomes. Significantly, the phylogenetic
      tree based on the ORF1b or ORF7 genes most closely resembled the tree based on
      the full-length genomes. Thus, these single genes will be the most useful in
      revealing the genetic relationships between the different strains relative to
      their geographical distribution. Extensive phylogenetic analyses using the ORF7
      sequences of 111 PRRSV isolates available revealed that PL97-1 is most closely
      related to the North American genotype VR-2332, a VR-2332-derived vaccine strain,
      and Chinese BJ-4. It is distantly related to the European genotype Lelystad. This
      study provides the largest full-length genome phylogenetic analysis of PRRSV that
      has been published to date, and supports an earlier genetic grouping of the many
      temporally and geographically diverse PRRSV strains currently isolated.

PMID- 15246655
TI  - Analysis of early region 4 of porcine adenovirus type 3.
AB  - The early region 4 (E4) of porcine adenovirus (PAdV)-3, located at the right-hand
      end of the genome is transcribed in a leftward direction and has the potential to
      encode seven (p1-p7) open reading frames (ORFs). To determine the role of each
      protein in viral replication, we constructed full-length PAdV-3 genomic clones
      containing deletions of individual E4 ORF or combined deletions of the
      neighboring ORFs. Transfection of swine testicular (ST) cells with individual E4
      mutant plasmid DNAs generated PAdV-3 E4 mutant viruses except with plasmids
      containing a deletion of ORF p3, ORF p2+ p3 or ORF p3+ p4. Each of the mutants
      was further analyzed for growth kinetics, and early/late protein synthesis.
      Mutant viruses carrying deletions in ORF p1, ORF p2 or ORF p4 showed growth
      characteristics similar to that of wild-type PAdV-3. Early/late protein synthesis
      was also indistinguishable from that of wild-type PAdV-3. However, mutant viruses
      carrying deletions in ORF p5, ORF p6 or ORF p7 showed a modest effect in their
      ability to grow in porcine cells and express early proteins. These results
      suggest that the E4 ORF p3 (showing low homology with non-essential human
      adenovirus (HAdV)-9-E4 ORF1 encoded proteins) is essential for the replication of
      PAdV-3 in vitro. In contrast, the E4 ORF p7 (showing homology to essential HAdV-2
      34 kDa protein) is not essential for replication of PAdV-3 in vitro. Moreover,
      successful deletion of 1.957 kb fragment in E4 region increased the available
      capacity of replication-competent PAdV-3 (E3 + E4 deleted) to approximately 4.3
      kb and that of replication-defective PAdV-3 (E1 + E3 + E4 deleted) to
      approximately 7 kb. This is extremely useful for the construction of PAdV-3
      vectors that express multiple genes and/or regulatory elements for gene therapy
      and vaccination.

PMID- 15246656
TI  - Phosphoprotein P of Rinderpest virus binds to plus sense leader RNA: regulation
      by phosphorylation.
AB  - The negative sense genome RNA of Rinderpest virus, a Paramyxoviridae, is
      encapsidated with the nucleocapsid protein N and serves as a template for the
      viral RNA dependent RNA polymerase for transcription and replication. The viral
      RNA polymerase consists of the large protein L and the phosphoprotein P
      functioning as the P-L complex. We provide in this report, evidences for specific
      binding of P protein of Rinderpest virus to the plus sense leader RNA depending
      on its phosphorylation status. We have also demonstrated that P protein is
      released from the le RNA:P protein complex upon phosphorylation in vitro.
      Finally, we have identified that the C-terminal 358-389 amino acid residues of P
      protein is involved in le RNA binding. The leader RNA binding may signify a
      hitherto unidentified role for P protein in the viral RNA synthesis. Moreover,
      our results indicate a possible role for P protein in the transcription
      replication switch through leader RNA binding.

PMID- 15246657
TI  - Molecular epidemiology of canid rabies in Sudan: evidence for a common origin of
      rabies with Ethiopia.
AB  - Rabies is an endemic zoonosis in Sudan with the principal reservoir species being
      the domestic dog. A panel of rabies virus isolates from dogs in Sudan have been
      used to establish a molecular phylogeny based on a partial sequence of the viral
      nucleoprotein. These isolates were then compared to those from countries
      bordering Sudan in north-east Africa. The Sudanese viruses form a tight cluster
      of isolates with a single outlier. When compared to other African viruses, the
      Sudanese isolates cluster most closely with isolates from Ethiopia to the East
      suggesting a common origin for rabies in both countries which supports historical
      records of the movement of rabies into Sudan. The Sudanese group of viruses
      belong to the Africa 1a group of viruses that are present throughout much of
      north Africa.

PMID- 15246658
TI  - cis-Acting packaging motifs of porcine adenovirus type 3.
AB  - The cis-acting packaging domain is required for selective encapsidation of
      adenovirus DNA into preformed empty capsids late in the viral life cycle.
      Earlier, it was demonstrated that the cis-acting packaging domain of porcine
      adenovirus type (PAdV)-3 is located between nucleotide position (nt) 212 and 531
      at the left end genome which contains six AT/GC rich motifs. Removal of packaging
      domain from left end to the right end of the genome produced a viable mutant
      virus suggesting that the identified cis-acting packaging domain represents the
      DNA sequences required for selective packaging of PAdV-3 DNA, whose position and
      orientation appear to be flexible. Here, by constructing and analyzing a panel of
      virus mutants carrying deletions or linker scanning mutations in AT/GC rich
      sequences, we examined the significance of the continuous A/T or G/C sequences
      individually in the viral packaging process. In contrast to consensus bipartite
      structure (5'-TTTGN8CG-3') described for most of packaging motifs of human
      adenovirus type 5 (HAdV-5), the packaging motifs I, II, III, and IV of PAdV-3
      displayed a tripartite structure in which the continuous A/T nucleotides were
      flanked by G/C-rich sequences. Mutations in both continuous A/T nucleotides and
      its flanking GC-rich sequences reduced the packaging efficiency of mutants to
      varying degrees. In addition, although the continuous A/T sequences were present
      in all of the packaging motifs, their significance in the packaging process
      appears to vary within each packaging motif.

PMID- 15246659
TI  - Flower color modulations of Torenia hybrida by downregulation of chalcone
      synthase genes with RNA interference.
AB  - Suppression of biosynthetic genes involved in flower color formation is an
      important approach for obtaining target flower colors. Here we report that flower
      color of the garden plant Torenia hybrida was successfully modulated by RNA
      interference (RNAi) against a gene of chalcone synthase (CHS), a key enzyme for
      anthocyanin and flavonoid biosynthesis. By using each of the coding region and
      the 3'-untranslated region of the CHS mRNA as an RNAi target, exhaustive and gene
      specific gene silencing were successfully induced, and the original blue flower
      color was modulated to white and pale colors, respectively. Our results indicate
      that RNAi is quite useful for modulations of flower colors of commercially
      important garden plants.

PMID- 15246660
TI  - Expression of fungal pectin methylesterase in transgenic tobacco leads to
      alteration in cell wall metabolism and a dwarf phenotype.
AB  - A transgenic tobacco plant (Nicotiana tabacum L.) expressing a fungal pectin
      methylesterase (PME; EC 3.1.1.11) gene derived from a black filamentous fungus,
      Aspergillus niger was created. Fungal PME should have a wider range of
      adaptability to substrate pectin compared with plant PME. As expected, the
      proportion of methyl esters in pectin was reduced in the transgenic tobacco.
      Consequently, the transgenic plant showed short internodes, small leaves and a
      dwarf phenotype. At a cellular level, the longitudinal lengths of stem epidermal
      cells were shorter than those of control plants. This is the first report that
      fungal PME promotes dwarfism in plants. It is worth noting that in the PME
      expressing dwarf plant, the expression levels of cell wall metabolism related
      genes that included endo-1,4-beta-glucanase, cellulose synthase, endo-xyloglucan
      transferase and expansin gene were decreased. These results suggest that the
      expression of fungal PME in plants affects the cell wall metabolism.

PMID- 15246661
TI  - Expression of human VEGF165 in silkworm (Bombyx mori L.) by using a recombinant
      baculovirus and its bioactivity assay.
AB  - Silkworm larva has a lot of advantages as a "biofactory" to produce recombinant
      protein. A recombinant baculovirus, carrying cDNA encoding the 165 amino-acid
      long isoform of human vascular endothelial growth factor (VEGF) was successfully
      constructed for the large-scale production of this protein using silkworms as an
      in vivo host. The fifth-instar silkworm larvae were inoculated with the
      recombinant virus. Time-course expression analysis indicated that the expression
      level was highest at around 80 h post-infection and the recombinant protein was
      found mainly in the haemolymph. Therefore, the hemolymph was collected from the
      infected larvae and the recombinant protein was purified by using Nickel affinity
      chromatography under native condition. The expression level was estimated to be
      as high as approximately 426 microg per larva. Furthermore, the recombinant
      protein was characterized and was found biologically active in inducing
      endothelial cell proliferation in vitro.

PMID- 15246662
TI  - Analysis of genetic relationships among Rosa damascena plants grown in Turkey by
      using AFLP and microsatellite markers.
AB  - Rosa damascena Mill. is the most important rose species for rose oil production.
      The main rose oil producers in the world are Turkey and Bulgaria and they obtain
      the rose oil almost exclusively from R. damascena. In spite of coming from the
      same original populations, R. damascena plants grown in Turkey show some
      morphological differences. In this study, it was aimed to investigate the genetic
      relationships among R. damascena plants grown in Turkey by using microsatellite
      and AFLP markers. Twenty three AFLP and nine microsatellite primer pairs were
      used for this aim. No polymorphism could be detected among the plants, as the
      marker patterns obtained from different plants are identical. The conclusion from
      these data is that all R. damascena plants under study are derived from the same
      original genotype by vegetative propagation. Furthermore, the observed
      morphological differences originate from point mutations not detectable by
      molecular markers. Therefore, they are equivalent to sport mutations frequently
      observed in cut and garden rose varieties.

PMID- 15246663
TI  - Protein thermostability: structure-based difference of amino acid between
      thermophilic and mesophilic proteins.
AB  - Structural distributions of each amino acid were compared between 20 pairs of
      thermophilic and mesophilic proteins to obtain thermostable factors. Five kinds
      of residual structure states such as fully-exposed, exposed, partially exposed
      (or partially buried), buried, well-buried states were considered for analyzing
      the structural patterns of amino acids. The statistical tests revealed that lower
      frequency in partially exposed state of SER, lower frequency in exposed state and
      higher frequency in well-buried state of ALA, higher frequency in buried state of
      GLU, higher frequency in exposed state of ARG, etc. could be critical factors
      related with protein thermostability.

PMID- 15246664
TI  - Ultra-stable zeolites--a tool for in-cell chemistry.
AB  - Ultrastable zeolite particles were used as vehicles to carry low molecular bio
      active substances and macromolecules as proteins into viable cells. Zeolite
      particles that can be used for internalisation by phagocytosis were obtained from
      the non-sedimenting fraction of a commercially available zeolite preparation
      after 1 x g sedimentation. Protein adsorbed on the zeolite surface was shown to
      enter the endosomal pathway after phagocytosis and could be cleaved by the
      endosomal proteases. As a model of a low molecular weight bio-active molecule,
      the inhibitor of the cellular synthesis of nitrogen oxide, N-nitro-L-arginine
      methyl ester (L-NAME), was used. A partial inhibition of the cellular NO
      production was shown after utilizing zeolites as vehicles to introduce the
      inhibitor into the cells. A targeting of the intra-cellular enzymes that was at
      least 10 times more efficient was obtained by the use of zeolites as a carrier of
      the inhibitor, as opposed to addition of the inhibitor to the culture medium.

PMID- 15246665
TI  - Development of an efficient enzymatic production of gamma-D-glutamyl-L-tryptophan
      (SCV-07), a prospective medicine for tuberculosis, with bacterial gamma
      glutamyltranspeptidase.
AB  - Gamma-D-Glutamyl-L-tryptophan (SCV-07) is a prospective medicine for the
      treatment of tuberculosis, according to the phase two clinical trial. Because
      gamma-D-glutamyl-L-tryptophan has several reactive groups in its molecule,
      consists of D- and L-amino acids, and is connected by gamma-glutamyl linkage, its
      chemical synthesis is complicated. An efficient enzymatic method to synthesize
      gamma-D-glutamyl-L-tryptophan from D-glutamine and L-tryptophan employing
      bacterial gamma-glutamyltranspeptidase was developed. The optimum reaction
      conditions were 50 mM D-glutamine, 50 mM L-tryptophan, and 0.2 U ml(-1) gamma
      glutamyltranspeptidase, pH 9-9.5, and incubation at 37 degrees C for 5 h. After a
      5 h incubation, 33 mM gamma-D-glutamyl-L-tryptophan was obtained, the conversion
      rate being 66%. The product was purified by Dowex 1 x 8 column and was considered
      to be gamma-D-glutamyl-L-tryptophan.

PMID- 15246666
TI  - Anaerobic bio-hydrogen production from ethanol fermentation: the role of pH.
AB  - Hydrogen was produced by an ethanol-acetate fermentation at pH of 5.0 +/- 0.2 and
      HRT of 3 days. The yield of hydrogen was 100-200 ml g Glu(-1) with a hydrogen
      content of 25-40%. This fluctuation in the hydrogen yield was attributed to the
      formation of propionate and the activity of hydrogen utilizing methanogens. The
      change in the operational pH for the inhibition of this methanogenic activity
      induced a change in the main fermentation pathway. In this study, the main
      products were butyrate, ethanol and propionate, in the pH ranges 4.0-4.5, 4.5-5.0
      and 5.0-6.0, respectively. However, the activity of all the microorganisms was
      inhibited below pH 4.0. Therefore, pH 4.0 was regarded as the operational limit
      for the anaerobic bio-hydrogen production process. These results indicate that
      the pH plays an important role in determining the type of anaerobic fermentation
      pathway in anaerobic bio-hydrogen processes.

PMID- 15246667
TI  - Production of fungal alpha-amylase by Saccharomyces kluyveri in glucose-limited
      cultivations.
AB  - Heterologous protein production by the yeast Saccharomyces kluyveri was
      investigated under aerobic glucose-limited conditions. Alpha-amylase from
      Aspergillus oryzae was used as model protein and the gene was expressed from a S.
      cerevisiae 2 micro plasmid. For comparison, strains of both S. kluyveri and S.
      cerevisiae were transformed with the same plasmid, which led to secretion of
      active alpha-amylase in both cases. The S. cerevisiae 2 micro plasmid was found
      to be stable in S. kluyveri as evaluated by a constant alpha-amylase productivity
      in a continuous cultivation for more than 40 generations. S. kluyveri and S.
      cerevisiae secreted alpha-amylase with similar yields during continuous
      cultivations at dilution rates of 0.1 and 0.2 h(-1) (4.8-5.7 mg (g dry weight)(
      1)). At a dilution rate of 0.3 h(-1) the metabolism of S. kluyveri was fully
      respiratory, whereas S. cerevisiae produced significant amounts of ethanol. A fed
      batch cultivation was carried out with S. kluyveri where the biomass
      concentration reached 85 g l(-1) and the alpha-amylase concentration reached 320
      mg l(-1). Even though S. kluyveri could be grown to high cell density, it was
      also observed that it has a high maintenance coefficient, which resulted in low
      biomass yields at the low specific growth rates prevailing towards the end of the
      fed-batch cultivation.

PMID- 15246668
TI  - High yields of stable and highly pure nucleocapsid proteins of different
      hantaviruses can be generated in the yeast Saccharomyces cerevisiae.
AB  - Recently, the high-level expression of authentic and hexahistidine (His)-tagged
      Puumala (strain Vranica/Hallnas) hantavirus nucleocapsid protein derivatives in
      the yeast Saccharomyces cerevisiae has been reported [Dargeviciute et al.,
      Vaccine, 20 (2002) 3523-3531]. Here we describe the expression of His-tagged
      nucleocapsid proteins of other Puumala virus strains (Sotkamo, Kazan) as well as
      Dobrava (strains Slovenia and Slovakia) and Hantaan (strain Fojnica) hantaviruses
      using the same system. All nucleocapsid proteins were expressed in the yeast S.
      cerevisiae at high levels. The nucleocapsid proteins can be easily purified by
      nickel chelate chromatography; the yield for all nucleocapsid proteins ranged
      from 0.5 to 1.5 mg per g wet weight of yeast cells. In general, long-term storage
      of all nucleocapsid proteins without degradation can be obtained by storage in
      PBS at -20 degrees C or lyophilization. The nucleocapsid protein of Puumala virus
      (strain Vranica/Hallnas) was demonstrated to contain only traces of less than 10
      pg nucleic acid contamination per 100 microg of protein. The yeast-expressed
      nucleocapsid proteins of Hantaan, Puumala and Dobrava viruses described here
      represent useful tools for serological hantavirus diagnostics and for vaccine
      development.

PMID- 15246669
TI  - Real time in situ microscopy for animal cell-concentration monitoring during high
      density culture in bioreactor.
AB  - An in situ microscope (ISM) device is utilised in this study to monitor hybridoma
      cells concentration in a stirred bioreactor. It generates images by using pulsed
      illumination of the liquid broth synchronised with the camera frame generation to
      avoid blur from the cell's motion. An appropriate image processing isolates the
      sharp objects from the blurred ones that are far from the focal plane. As image
      processing involves several parameters, this paper focuses on the robustness of
      the results of the cells counting. This stage determines the applicability of the
      measuring device and has seldom been tackled in the presentations of ISM devices.
      Calibration is secondly performed for assessing the cell-concentration from the
      cell automated numeration provided by the ISM. Flow cytometry and hemacytometer
      chamber were used as reference analytical methods. These measures and the output
      of the image processing allow estimating a single calibration parameter: the
      reference volume per image equal to 1.08 x 10(-6) mL. In these conditions, the
      correlation coefficient between both reference and ISM data sets becomes equal to
      0.99. A saturation of this system during an ultrasonic wave perfusion phase that
      deeply changes the culture conditions is observed and discussed. Principal
      component analysis (PCA) is used to undergo the robustness study and the ISM
      calibration step.

PMID- 15246670
TI  - Cortical auditory evoked potentials in autism: a review.
AB  - The question of etiology in autism remains elusive primarily due to the fact that
      autism does not result from a single dysfunction but is multi-faceted in nature.
      Investigations into etiology have ranged from identifying abnormalities in the
      genome to describing structural/functional brain abnormalities. Bearing in mind
      the risk of over-simplification, there is still utility in isolating a specific
      deficit to examine its etiologic contribution. It is known that individuals with
      autism have difficulty processing auditory information at the cortical level but
      this is not consistently seen subcortically. In recent years, cortical auditory
      processing has been extensively researched using event-related potentials (ERPs);
      however, these results in relation to autism have not been reviewed. This paper
      will examine this literature and discuss implications for future research.

PMID- 15246671
TI  - Electrodermal dissociation of chronic fatigue and depression: evidence for
      distinct physiological mechanisms.
AB  - Chronic fatigue syndrome (CFS) has an estimated prevalence between 0.5% and 3%,
      yet its diagnosis remains contentious. CFS is characterized by subjective
      symptoms that can be difficult to verify; moreover, depression is a commonly
      reported CFS complaint, whereas fatigue is a common symptom of depression. Our
      primary goal was dissociation of these disorders using psychophysiological
      methods. As previous research has implicated the autonomic nervous system in CFS,
      we conducted what we believe to be the first analysis of bilateral electrodermal
      and skin temperature responses of dextral females in a cross-modal orienting
      task, to investigate differences between these two patient groups and controls. A
      multivariate analysis of variance (MANOVA) examining three measures of
      electrodermal activity revealed prestimulus tonic skin conductance levels (SCLs)
      were markedly lower for the CFS group, with no difference between controls and
      depressives. Concurrent skin temperature levels were higher for the CFS group
      than the other two groups. These findings indicate that, despite overtly similar
      cognitive and symptom profiles, depression and CFS patients can be differentiated
      with psychophysiological measures. This study adds to the growing body of
      evidence demonstrating that CFS and depression have distinct neurobiological
      profiles, consistent with unique aetiologies.

PMID- 15246672
TI  - Alexithymia predicts attenuated autonomic reactivity, but prolonged recovery to
      anger recall in young women.
AB  - Alexithymia has been prospectively associated with all-cause mortality and with
      cardiovascular morbidity. Here, stress-induced autonomic reactivity and recovery
      were examined as potential pathways linking alexithymia to cardiovascular
      disease. The relation of alexithymia to blood pressure, heart rate, and other
      cardiovascular parameters derived from impedance cardiography (N = 80) and heart
      rate variability (N = 40) was evaluated during rest, an anger recall task and
      recovery in women (ages 18-30). During anger recall, alexithymia was associated
      with significantly attenuated heart rate and stroke index reactivity, greater low
      frequency power, and with marginally dampened blood pressure and high frequency
      power reactivity. Overall, this response pattern suggests blunted sympathetic
      activation and diminished vagal withdrawal. Alexithymia was also related to
      slower diastolic blood pressure and quicker preejection period recovery implying
      abbreviated sympathetic arousal and possibly greater vagal modulation. These
      results impart some evidence for the hypoarousal model of alexithymia during
      reactivity, but the hyperarousal model during recovery. Autonomic dysregulation
      during and following acute emotional stress is suggested as a possible
      physiological pathway connecting alexithymia to cardiovascular disease.

PMID- 15246673
TI  - Effects of stimulus repetitions on the event-related potential of humans and
      rats.
AB  - The present study compared the effects of repeated stimulus presentations on the
      event-related potential (ERP) of humans and rats. Both species were presented
      with a total of 100 auditory stimuli, divided into four blocks of 25 stimuli. By
      means of wavelet denoising, single-trial ERPs were established in both humans and
      rats. The auditory ERPs were characterized by the presence of two positive and
      two negative waves in both humans and rats, albeit with different latencies in
      the two species (P1, N1, P2, and N2). The results showed decreased amplitudes
      within blocks for the N1, P2, and N2 components in humans and for the N1 and P2
      components in rats. Decreased amplitudes across blocks were found for the N2
      component in humans and for the P2 and N2 components in rats. In both humans and
      rats, response decrements within a block were thus most prominent for the early
      ERP components, whereas the changes across blocks were most prominent for the
      later components. These results suggest a correspondence of the ERP correlates of
      elemental stimulus processing between humans and rats. It is further suggested
      that the observed amplitude reductions may reflect habituation and/or recovery
      cycle processes.

PMID- 15246674
TI  - Specific EEG frequencies signal general common cognitive processes as well as
      specific task processes in man.
AB  - The EEG of 10 normal male young adults was recorded during the performance of
      three different tasks: mental calculation, verbal working memory (VWM) and
      spatial working memory (SWM). The stimuli used in the three tasks were the same,
      only the instructions to the subjects were different. Narrow band analysis of the
      EEG and distributed sources for each EEG frequency were calculated using variable
      resolution electromagnetic tomography (VARETA). At some frequencies (1.56, 4.68,
      7.80 to 10.92 Hz) at least two tasks produced similar EEG patterns that were
      interpreted as the reflex of common cognitive processes, such as attention,
      inhibition of irrelevant stimuli, etc. Specific changes were also observed at
      2.34, 3.12, 3.90, 5.46 and 6.24 Hz. The first three of these frequencies showed
      similar changes during VWM and calculus at the left frontal cortex, suggesting
      the activation of working memory (WM) processes. The interaction effect at these
      frequencies was mainly observed at the anterior cingulate cortex and frontal
      cortex. At 5.46 and 6.24 Hz, changes were only observed during mental
      calculation.

PMID- 15246675
TI  - Event-related brain correlates of associative learning without awareness.
AB  - Controversy exists about whether associative learning occurs without awareness.
      In an earlier study using subthreshold (subliminal) stimuli, we reported evidence
      that such learning could occur as measured by event-related brain potentials
      [ERP; Cons. Cognit. 6 (1997) 519]. In the present study, we extend these findings
      by changing several aspects of the methodology in order to provide a more
      stringent test of this effect and to examine its generality. We used two matched
      words (murder and cancer) as conditional stimuli (CS); a 100 dB white noise blast
      as unconditional stimulus (US); a CS-US interval of 3 s; and a full-factorial
      design with CSs counterbalanced. The conditioning-acquisition phase occurred when
      the CSs were perceptually unconscious, as confirmed by a subsequent behavioral
      task. The conditioning-acquisition and postconditioning-extinction phases were
      examined for ERP evidence of associative learning. The clearest and strongest
      evidence for associative learning without awareness was observed in the ERP
      component measures (up to 1 s, poststimulus) in the postconditioning-extinction
      phase. The CS+ was significantly more positive than the CS- in the P3b-LP
      component region, which is highly consistent with the results of our earlier
      study. Differences also were observed in the P1-P2 components. In an unexpected
      finding, we observed a significant positive slow potential shift for the CS+ in
      the region between 1 and 3 s poststimulus. We discuss these results and their
      implications for our understanding of associative learning and awareness.

PMID- 15246676
TI  - Eliminating the P300 rebound in short oddball paradigms.
AB  - In short oddball paradigms, the P3 (or P300) amplitude often shows a curvilinear
      "rebound" pattern, such that an initial drop during the first few trials is
      followed by an increase in later trials. While the initial attenuation has been
      attributed to habituation, no explanation has been offered for the later
      increase. Our hypothesis was that this curvilinear pattern is due to anticipation
      of the end of each fixed-length block. In study 1, a series of 16 short, fixed
      length auditory oddball tests (with six targets each) replicated the rebound
      effect. In study 2, a further set of 16 variable-length blocks (7-10 targets)
      eliminated the rebound, and the P300 amplitude decreased linearly as expected.
      Results are interpreted in light of various constructs related to the P3:
      habituation, attentional salience, and updating in working memory.

PMID- 15246677
TI  - Mental effort affects vigilance enduringly: after-effects in EEG and behavior.
AB  - Vigilance is assumed to decline with sustained task performance. The EEG-effects
      during performance on mental tasks, however, cannot be ascribed indisputably to
      vigilance decline per se. During task performance itself, effects of information
      processing and vigilance decline may be confounded. In this study, effects of
      sustained mental effort were studied in the absence of specific information
      processing, after sustained information processing had taken place, namely after
      an effortful 70-min intelligence test. Vigilance was determined by means of EEG
      measures in a rest condition. Furthermore, behavioral performance was assessed on
      two different tasks, the traditional Clock test and the SART. After mental
      effort, theta power in the EEG and errors on the SART were increased. Beta2
      power, however, also appeared enhanced. We conclude that sustained mental effort
      produces an enduring decrease in vigilance, but that some active processing is
      enhanced at the same time. A second study replicated the EEG-results after mental
      effort.

PMID- 15246678
TI  - Integrating an integrin: a direct route to actin.
AB  - Integrins were so named for their ability to link the extracellular and
      intracellular skeletons. Now almost 20 years into integrin research, numerous
      questions remain as to how this interaction is accomplished and how it is
      modified to achieve a desired phenotype. As the cell adhesion and actin assembly
      fields are merging in combined approaches, novel actin assembly mechanisms are
      being uncovered. Some of the earliest identified cytoplasmic linker molecules,
      believed to mediate integrin-actin binding, are once again the subject of
      scrutiny as potential dynamic mediators of cell anchorage. It seems plausible
      that each unique cellular morphology occurs as the result of activation of
      distinct actin assembly systems that are either stabilized by unique bundling and
      linker proteins or modified for progression to a new phenotype. While this
      research initiative is likely to continue rapidly in a forward fashion, it
      remains to be clarified how integrins assemble the most stable and basic
      cytoskeletal phenotype, the adherent cell with prominent stress fibers. Recent
      investigations point towards a shift in the current model of anchoring at the
      cell periphery by providing both mechanisms and evidence for de novo actin
      assembly orchestrated by the adhesion site. Lacking a complete pathway from
      integrin ligation to an integrated extracellular-intracellular skeleton in any
      single system, this review proposes a simple model of integrin-mediated stress
      fiber integration by drawing from work in multiple systems.

PMID- 15246679
TI  - The PINCH-ILK-parvin complexes: assembly, functions and regulation.
AB  - Cell-extracellular matrix (ECM) adhesion is mediated by transmembrane cell
      adhesion receptors (e.g., integrins) and receptor proximal cytoplasmic proteins.
      Over the past several years, studies using biochemical, structural, cell
      biological and genetic approaches have provided important evidence suggesting
      crucial roles of integrin-linked kinase (ILK), PINCH and CH
      ILKBP/actopaxin/affixin/parvin (abbreviated as parvin herein) in ECM control of
      cell behavior. One general theme emerging from these studies is that the
      formation of ternary protein complexes consisting of ILK, PINCH and parvin is
      pivotal to the functions of PINCH, ILK and parvin proteins. In addition, recent
      studies have begun to uncover the molecular mechanisms underlying the assembly,
      functions and regulation of the PINCH-ILK-parvin (PIP) complexes. The PIP
      complexes provide crucial physical linkages between integrins and the actin
      cytoskeleton and transduce diverse signals from ECM to intracellular effectors.
      Among the challenges of future studies are to define the functions of different
      PIP complexes in various cellular processes, identify additional partners of the
      PIP complexes that regulate and/or mediate the functions of the PIP complexes,
      and determine the roles of the PIP complexes in the pathogenesis of human
      diseases involving abnormal cell-ECM adhesion and signaling.

PMID- 15246680
TI  - Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk
      scaffold.
AB  - The molecular coupling of CAS and Crk in response to integrin activation is an
      evolutionary conserved signaling module that controls cell proliferation,
      survival and migration. However, when deregulated, CAS/Crk signaling also
      contributes to cancer progression and developmental defects in humans. Here we
      highlight recent advances in our understanding of how CAS/Crk complexes assemble
      in cells to modulate the actin cytoskeleton, and the molecular mechanisms that
      regulate this process. We discuss in detail the spatiotemporal dynamics of
      CAS/Crk assembly and how this scaffold recruits specific effector proteins that
      couple integrin signaling networks to the migration machinery of cells. We also
      highlight the importance of CAS/Crk signaling in the dual regulation of cell
      migration and survival mechanisms that operate in invasive cells during
      development and pathological conditions associated with cancer metastasis.

PMID- 15246681
TI  - Control of motile and invasive cell phenotypes by focal adhesion kinase.
AB  - Cell motility is stimulated by extracellular stimuli and initiated by
      intracellular signaling proteins that localize to sites of cell contact with the
      extracellular matrix termed focal contacts. Focal adhesion kinase (FAK) is an
      intracellular protein-tyrosine kinase (PTK) that acts to regulate the cycle of
      focal contact formation and disassembly required for efficient cell movement. FAK
      is activated by a variety of cell surface receptors and transmits signals to a
      range of targets. Thus, FAK acts as an integrator of cell motility-associated
      signaling events. We will review the stimulatory and regulatory mechanisms of FAK
      activation, the different signaling connections of FAK that are mediated by a
      growing number of FAK-interacting proteins, and the modulation of FAK function by
      tyrosine and serine phosphorylation. We will also summarize findings with regard
      to FAK function in vertebrate and invertebrate development as well as recent
      insights into the mechanistic role(s) of FAK in promoting cell migration. As
      increased FAK expression and tyrosine phosphorylation have been correlated with
      the progression to an invasive cell phenotype, there is growing interest in
      elucidating the important FAK-related signaling connections promoting invasive
      tumor cell movement. To this end, we will discuss the effects of FAK inhibition
      via the dominant-negative expression of the FAK C-terminal domain termed FAK
      related non-kinase (FRNK) and how these studies have uncovered a distinct role
      for FAK in promoting cell invasion that may differ from its role in promoting
      cell motility.

PMID- 15246682
TI  - Focal adhesion regulation of cell behavior.
AB  - Focal adhesions lie at the convergence of integrin adhesion, signaling and the
      actin cytoskeleton. Cells modify focal adhesions in response to changes in the
      molecular composition, two-dimensional (2D) vs. three-dimensional (3D) structure,
      and physical forces present in their extracellular matrix environment. We
      consider here how cells use focal adhesions to regulate signaling complexes and
      integrin function. Furthermore, we examine how this regulation controls complex
      cellular behaviors in response to matrices of diverse physical and biochemical
      properties. One event regulated by the physical structure of the ECM is
      phosphorylation of focal adhesion kinase (FAK) at Y397, which couples FAK to
      several signaling pathways that regulate cell proliferation, survival, migration,
      and invasion.

PMID- 15246683
TI  - Cell adhesion receptors, tyrosine kinases and actin modulators: a complex three
      way circuitry.
AB  - The interaction of cells with surrounding matrix and neighbouring cells governs
      many aspects of cell behaviour. Aside from transmitting signals from the external
      environment, adhesion receptors also receive signals from the cell interior. Here
      we review the interrelationship between adhesion receptors, tyrosine kinases
      (both growth factor receptor and non-receptor) and modulators of the actin
      cytoskeletal network. Deregulation of many aspects of these signalling pathways
      in cancer highlights the need for a better understanding of the complexities
      involved.

PMID- 15246684
TI  - Regulation of Bcl-2 proteins during anoikis and amorphosis.
AB  - Adhesion to extracellular matrix regulates cell survival through both integrin
      engagement and appropriate cell spreading. Numerous signaling pathways converge
      to affect the levels and posttranslational modifications of Bcl-2 family
      proteins. Recent work has defined specific roles for different Bcl-2 proteins in
      the disruption of mitochondrial function that leads to cell death. Using this
      understanding of Bcl-2 protein function as a framework, we will consider the
      molecular mechanisms of apoptosis induced by integrin detachment (anoikis) and
      cell death stimulated by the loss of cytoskeletal architecture (amorphosis).

PMID- 15246685
TI  - Regulation of actin-based cell migration by cAMP/PKA.
AB  - A wide variety of soluble signaling substances utilize the cyclic AMP-dependent
      protein kinase (PKA) pathway to regulate cellular behaviors including
      intermediary metabolism, ion channel conductivity, and transcription. A growing
      literature suggests that integrin-mediated cell adhesion may also utilize PKA to
      modulate adhesion-associated events such as actin cytoskeletal dynamics and
      migration. PKA is dynamically regulated by integrin-mediated cell adhesion to
      extracellular matrix (ECM). Furthermore, while some hallmarks of cell migration
      and cytoskeletal organization require PKA activity (e.g. activation of Rac and
      Cdc42; actin filament assembly), others are inhibited by it (e.g. activation of
      Rho and PAK; interaction of VASP with the c-Abl tyrosine kinase). Also, cell
      migration and invasion can be impeded by either inhibition or hyper-activation of
      PKA. Finally, a number of A-kinase anchoring proteins (AKAPs) serve to associate
      PKA with various components of the actin cytoskeleton, thereby enhancing and/or
      specifying cAMP/PKA signaling in those regions. This review discusses the growing
      literature that supports the hypothesis that PKA plays a central role in
      cytoskeletal regulation and cell migration.

PMID- 15246687
TI  - Structure-activity comparison of organotin species: dibutyltin is a developmental
      neurotoxicant in vitro and in vivo.
AB  - Human exposure to the organotins can occur due to their use as polyvinyl chloride
      heat stabilizers and as marine biocides. The consequences of this exposure for
      human health are unknown. We initially compared the toxicity of monomethyltin,
      dimethyltin, and dibutyltin to the known neurotoxicant trimethyltin using an in
      vitro model of neuronal development in PC12 cells. Dibutyltin, a compound
      traditionally thought to target the immune system, was the most potent
      neurotoxicant. Dibutyltin significantly inhibited neurite outgrowth and caused
      cell death at concentrations approximately 40-fold lower than the lowest toxic
      concentrations of trimethyltin. Dimethyltin was less potent than trimethyltin and
      monomethyltin was not toxic at any concentration examined. These results
      suggested the importance of prioritizing in vivo neurotoxicity testing with
      dibutyltin. To accomplish this, pregnant rats were dosed orally with low levels
      of dibutyltin from gestational day 6 through weaning. In response to
      developmental dibutyltin exposure, the incidence of apoptotic cell death,
      measured by DNA fragmentation and TUNEL staining, was increased in the neocortex
      and hippocampus of postnatal day 38 offspring. No effect was observed at other
      ages examined.

PMID- 15246689
TI  - Localization of synapsin-I and PSD-95 in developing postnatal rat cerebellar
      cortex.
AB  - The comparative localization of two prominent synaptic proteins, synapsin-I (Syn
      I) and PSD-95, was investigated in slices of developing (P3-P21) rat cerebellar
      cortex using double- or triple-label fluorescence immunohistochemistry and
      confocal microscopy. During the first postnatal week, Syn-I and PSD-95
      immunoreactive (IR) puncta were strongly concentrated in the Purkinje cell layer
      (PCL) where they circumscribed irregularly shaped PC somata, forming pericellular
      nests that likely correspond to early climbing fiber synapses. PSD-95 and Syn-I
      puncta also were found along the shafts and at the tips of growing PC dendrite
      branches labeled with calbindin. During the second postnatal week, synaptic
      puncta were lost from the PC layer, while many new puncta were added to the
      molecular layer (ML). At P10, about half of the PCs were circumscribed by PSD-95
      or Syn-I puncta, whereas at P14 no PCs were circumscribed. By P14, PSD-95 and Syn
      I became most strongly localized to many small puncta in the ML and to large
      clusters at mossy fiber rosettes in the glomerular layer (GL) where PSD-95 often
      encircled Syn-I clusters. Some large clusters in the GL contained only PSD-95 or
      Syn-I, but not both, suggesting differential growth or remodeling of pre- and
      post-synaptic structures. No PSD-95 staining of pre-synaptic terminal pinceau was
      observed during the first 3 weeks of postnatal development. Thus, in relation to
      PCs, there is a developmental shift in PSD-95 localization whereby, first, it is
      concentrated on PC cell bodies and short dendrites (P3-P7), then it is lost on PC
      cell bodies (P7-14) and becomes localized almost exclusively to PC dendrites (P14
      P21).

PMID- 15246688
TI  - Nestin expression is lost in a neural stem cell line through a mechanism
      involving the proteasome and Notch signalling.
AB  - Neural stem cells (NSCs) are believed to repair brain damage primarily through
      cell replacement: i.e., the ability to regenerate lost neurons and glia in a site
      specific fashion. The neural stem cell line, MHP36, has been shown to have this
      capacity, but we have little idea of the molecular mechanisms that control the
      differentiation of such cells during brain repair. In this study we show that an
      early event in the differentiation of MHP36 cells, both in vivo and in vitro, is
      the loss of expression of the intermediate filament protein, nestin. We use a co
      culture assay to show that loss of nestin is fast, being detectable after just 1
      h and complete in 4 h, and is controlled by proteasome degradation rather than
      down-regulation of de novo nestin synthesis. We also show that nestin loss is
      regulated by Notch, and mediated by cell contact.

PMID- 15246690
TI  - The calcium pump of the endoplasmic reticulum plays a role in midline signaling
      during early zebrafish development.
AB  - During early vertebrate development, a signaling network is activated along the
      midline of the embryo. This signaling network induces the neural tube floor plate
      and ventral brain regions. In turn, induction of the ventral brain region is
      important for bilateral division of the forebrain and bilateral separation of the
      eyes. The present study provides direct evidence for a role of the endoplasmic
      reticulum Ca(2+) pump in zebrafish midline signaling. The endoplasmic reticulum
      Ca(2+) pump was inhibited in zebrafish embryos using thapsigargin or
      cyclopiazonic acid. Inhibition of the endoplasmic reticulum Ca(2+) pump during
      early gastrulation induces cyclopia, mimicking defects observed in cyclops,
      squint, one-eyed pinhead, and silberblick mutant embryos. In contrast, inhibition
      of the endoplasmic reticulum Ca(2+) pump during mid-gastrulation does not induce
      cyclopia, but does induce tail defects, mimicking defects observed in no-tail
      mutant embryos. This study is the first to relate thapsigargin and cyclopiazonic
      acid with induction of cyclopia. In addition, obtained results provide new
      information on the roles of Ca(2+) in embryonic development and may lead to new
      insights on the mechanisms underlying holoprosencephaly, a relatively common
      brain defect in human development.

PMID- 15246691
TI  - The role of cell death during neocortical neurogenesis and synaptogenesis:
      implications from a computational model for the rat and mouse.
AB  - We are quantitatively evaluating the acquisition of neocortical neurons through
      key stages of development including neurogenesis, migration, and synaptogenesis.
      Here we expand upon a previous computational model describing neocortical
      neurogenesis in the rat and mouse [Dev. Neurosci. 24 (2002) 467], to include the
      period of synaptogenesis (P0-P14) when programmed cell death (PCD) is known to
      play a major role in shaping the neocortex. We also quantitatively evaluate
      differing hypotheses on the role of cell death during neurogenesis. This new
      model construct allows prediction of acquisition of adult neuronal number in the
      rat and mouse neocortex from the beginning of neurogenesis through
      synaptogenesis. The mathematical model output is validated by independently
      derived stereologically determined neuron number estimates in the adult rat and
      mouse. Simulations suggest cell death during synaptogenesis reduces the
      neocortical neuronal population by 20-30%, while cell death of progenitor cells
      and newly formed neurons during neurogenesis may reduce output by as much as 24%.
      However, higher death rates during neurogenesis as suggested by some research
      would deplete the progenitor population, not allowing for the vast expansion that
      is the hallmark of the mammalian neocortex. Furthermore, our simulations suggest
      the clearance time of dying neurons labeled by TUNEL or pyknosis is relatively
      short, between 1 and 4 h, corroborating experimental research. This novel
      mathematical model for adult neocortical neuronal acquisition allows for in
      silico analysis of normal and perturbed states of neocortical development as well
      as interspecies and evolutionary analyses of neocortical development.

PMID- 15246692
TI  - Local neurotrophin effects on central trigeminal axon growth patterns.
AB  - In dissociated cell and wholemount explant cultures of the embryonic trigeminal
      pathway NGF promotes exuberant elongation of trigeminal ganglion (TG) axons,
      whereas NT-3 leads to precocious arborization [J. Comp. Neurol. 425 (2000) 202].
      In the present study, we investigated the axonal effects of local applications of
      NGF and NT-3. We placed small sepharose beads loaded with either NGF or NT-3
      along the lateral edge of the central trigeminal tract in TG-brainstem intact
      wholemount explant cultures prepared from embryonic day 15 rats. Labeling of the
      TG with carbocyanine dye, DiI, revealed that NGF induces local defasciculation
      and diversion of trigeminal axons. Numerous axons leave the tract, grow towards
      the bead and engulf it, while some axons grow away from the neurotrophin source.
      NT-3, on the other hand, induced localized interstitial branching and formation
      of neuritic tangles in the vicinity of the neurotrophin source. Double
      immunocytochemistry showed that axons responding to NGF were predominantly TrkA
      positive, whereas both TrkA and TrkC-positive axons responded to NT-3. Our
      results indicate that localized neurotrophin sources along the routes of
      embryonic sensory axons in the central nervous system, far away from their parent
      cell bodies, can alter restricted axonal pathways and induce elongation,
      arborization responses.

PMID- 15246693
TI  - Increased baclofen-stimulated G protein coupling and deactivation in rat brain
      cortex during development.
AB  - The number and affinity of GABA(B) receptors (assayed by the specific antagonist
      [(3)H]CGP54626A) was unchanged when compared in carefully washed cerebrocortical
      membranes from young (12-day-old) and adult (90-day-old) rats. In contrast, high
      affinity GTPase activity, both basal and baclofen-stimulated was significantly
      higher (by 45% and 56%, respectively) in adult than in young rats. Similar
      results were obtained by concomitant determination of agonist (baclofen)
      stimulated GTP gamma S binding. Under standard conditions, baclofen-stimulated
      GTPase activity was further considerably enhanced by exogenously added regulator
      of G protein function, RGS1, but not by RGS16. RGS16 was able to affect agonist
      stimulated GTPase activity only in the presence of markedly increase substrate
      (GTP) concentrations. RGS1 alone slightly increased GTPase activity in adult
      rats, but neither RGS1 nor RGS16 influenced GTPase activity in membrane
      preparations isolated from young animals. These findings indicate increasing
      functional activity of trimeric G protein(s) involved in GABAergic transmission
      in the developing rat brain cortex and suggest a high potential of RGS1 in
      regulation of high-affinity GTPase activity.

PMID- 15246694
TI  - Distribution of presenilin 1 and 2 and their relation to Notch receptors and
      ligands in human embryonic/foetal central nervous system.
AB  - Notch signaling in vertebrates is mediated by four Notch receptors (Notch-1, -2, 
      3, and -4) that are activated by interacting with at least five different Notch
      ligands, Jagged-1, Jagged-2, Delta-1, -2, and -3. Recent studies have shown that
      the gamma-secretase-like intramembranous cleavage of Notch receptors to release
      their cytoplasmic signaling domains requires the presenilin (PS) proteins 1 and 2
      (PS1 and PS2). Here, we used immunohistochemistry to compare the distribution of
      all four Notch receptor proteins and three ligands in the context of co
      localization with PS1 and PS2 in first trimester human central nervous system
      (CNS). In addition, we investigated Notch receptors and ligands expression by
      Western blotting. The study was performed on the forebrain and spinal cord of
      human embryonic/foetal CNS (5-11 gestational weeks). Results showed a divergent
      distribution of the different Notch receptor proteins with only Notch-1 being co
      localized with PS1 and PS2. Notch-2 was only seen occasionally within the
      developing cortex and spinal cord. Notch-3 expression was restricted to
      neuroepithelial cells of the spinal cord and endothelial cells in blood vessels
      of both developing cerebral cortex and spinal cord. The weak, punctate staining
      of Notch-4 in the neuroepithelium of the spinal cord could not be confirmed with
      Western blotting. Neither Notch-2, nor -3 showed overlap with either PS1 or PS2
      immunoreactivity. The ligand Jagged-1 was found sporadically in the
      neuroepithelial cell layer in cerebral cortex of the earlier stages of
      development and of the spinal cord during the first trimester while Jagged-2 was
      not detected. Jagged-1 and Jagged-2 immunoreactivities were not found in the 9-11
      week cortex. No co-distribution of Jagged-1 and PS1 or PS2 was found. Delta-1
      ligand expression was detected in neuroepithelial cells of the ventricular zone
      of the cerebral cortex, and also in maturating neurons in the cortical plate and
      ventral horns of the developing spinal cord. The presence of Notch-1, Delta-1 and
      Jagged-1 in the neuroepithelium of developing CNS indicates that Notch signaling
      in proliferating human progenitor cells only involves these two receptor ligands
      and that cleavage of Notch-1 is mediated both by PS1 and PS2. The strong
      immunoreactivity of Notch-1, Delta-1 and PS1 in the cortical plate and in
      maturating neurons of the spinal cord also suggests that these proteins may
      regulate the maturation processes of post-mitotic neurons. The pronounced PS1
      immunoreactivity in neurites in the hindbrain and spinal cord without detectable
      expression of any Notch receptor or ligand suggests that a possible role for PS1
      in neurite growth involves either gamma-secretase-mediated cleavage of other
      substrates or gamma-secretase-independent mechanisms.

PMID- 15246695
TI  - Expression of alpha 5 GABAA receptor subunit in developing rat hippocampus.
AB  - The GABAergic system plays an important role in the hippocampal development. Here
      we have studied the developmental expression of the alpha 5 subunit of the
      GABA(A) receptor (from rat hippocampus) by RT-competitive PCR, immunoblot and
      immunocytochemistry. Our results demonstrated an early induction of the alpha 5
      subunit expression (at mRNA and protein levels) during the first postnatal week,
      peaking at P5 and decreasing after this age. The peak of alpha 5 subunit
      expression precedes the peak of expression for the synaptophysin, GAD65 and
      GAD67. Thus, the increase in the alpha 5 GABA(A) receptor subunit expression may
      precede the GABAergic synaptogenesis. Importantly, between P0 and P7, the
      expression of the alpha 5 subunit was concentrated at the cell somata of the
      pyramidal and granular cells. After P10, its localization shifted from the cell
      bodies to the dendritic layers. This developmental pattern is similar to that
      reported for the Na(+)-K(+)-2Cl(-) system and it might be correlated with the
      transition from excitatory to inhibitory GABAergic activity.

PMID- 15246696
TI  - Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor
      isoforms occur within hours of ethanol administration to 4-day-old rat pups.
AB  - Developing cerebellar Purkinje cells of the rat are extremely sensitive to
      ethanol during postnatal days (PN) 4-6, but not at later times during
      development. Ethanol exposure during this vulnerable window induces rapid
      apoptotic Purkinje cell death that is hypothesized to result from ethanol
      inhibition in brain-derived nerve growth factor (BDNF)-TrkB neurotrophic
      signaling that results in loss of apoptotic suppression. In this study, the
      effect that different concentrations of ethanol (1.5, 3.0, 4.5 and 6.0 g/kg) have
      on steady-state mRNA expression of BDNF and different TrkB receptor isoforms in
      the cerebellum on PN4 was determined at 1, 4, 6, and 8 h after treatment.
      Significant decreases in mRNA specific for BDNF and TrkB isoforms were detected
      within 1 h after ethanol administration. No significant alterations in expression
      of mRNA specific to the low affinity p75(NTR) receptor were identified. These
      alterations are concurrent with the PN4 vulnerable period for Purkinje cells
      since equivalent treatment of PN9 rat pups does not produce significant
      alterations in mRNA specific to BDNF or TrkB at 4 h after exposure. These results
      support the hypothesis that ethanol induces a disruption of BDNF-TrkB signaling
      that results in loss of apoptotic suppression in vulnerable Purkinje cells by
      growth factor withdrawal.

PMID- 15246697
TI  - Glycosyltransferase encoding gene EXTL3 is differentially expressed in the
      developing and adult mouse cerebral cortex.
AB  - Exostosin tumor-like 3 (EXTL3) is a glycosyltransferase involved in heparan
      sulfate (HS) biosynthesis. HS proteoglycans are critically involved in different
      steps during brain development. The present in situ hybridization in mice
      revealed wide EXTL3 expression at different grades in the central and peripheral
      nervous system components including the neural retina and neural crest-derived
      structures at embryonic days (E) 11.5, E12.5, E14.5, and E16.5. In the neopallial
      cortex, an intense EXTL3 expression was observed in the neuroepithelial cells
      lining the ventricular zone at E11.5 and E12.5. The signal decreased at E14.5 and
      was further downregulated at E16.5 in the ventricular zone. The pioneer neurons
      of the preplate at E12.5 differentially expressed the gene. Heavily stained among
      weakly or negatively stained neurons were observed. At E14.5, the cortical plate
      cells were moderately and homogeneously stained. In contrast, at E16.5, an
      upregulated and differential expression pattern was detected. The labeling
      pattern at E16.5 subdivided the cortical plate cells into a large number of
      heavily, a moderate number of less intensely, and some negatively stained cell
      populations. Interestingly, the distinct expression pattern displayed by the
      three main cell types of the adult cerebral cortex was similar to that of the
      late corticogenesis stage (E16.5). In the adult, the strongest expression was
      observed in the pyramidal neurons. The granule-type neurons showed less intense
      staining while the glia cells were devoid of signals. Our data revealed that
      EXTL3 expression is developmentally regulated in the mouse nervous system and
      suggested that it differentially contributes to brain development and
      corticogenesis.

PMID- 15246698
TI  - Corticotropin releasing factor enhances survival of cultured GABAergic cerebellar
      neurons after exposure to a neurotoxin.
AB  - Corticotropin-releasing factor (CRF), in addition to its role as a hormone in the
      stress response, functions as a neuromodulator in the cerebellum, where it
      enhances both the spontaneous and amino acid induced firing rate of Purkinje
      cells. In the cerebellum, CRF and its two types of receptors (CRF-R(1) and CRF
      R(2)) are present during cerebellar development at ages that precede the onset of
      afferent ingrowth and synaptogenesis, suggesting a distinct role during early
      cerebellar development. The present study was undertaken to determine whether CRF
      enhances the survival of cerebellar neurons, in particular GABAergic neurons.
      Primary cultures of cerebellar neurons obtained from embryonic day 18 mice were
      composed primarily, but not exclusively, of GABAergic neurons. Although CRF-R(1)
      is present in most neurons in this culture system, when CRF was added to the
      medium, no significant change in neuronal survival was observed when compared to
      control cultures. It is possible that a role for CRF is not seen in growth
      promoting culture medium at the plating density chosen for this study and may
      only be evident when the cells have been exposed to conditions that reduce the
      likelihood of survival, such as exposure to neurotoxins such as AraC. We propose
      that, because AraC increases the number of cleaved caspase-3 positive cells,
      indicating apoptosis, it is possible that a CRF effect involves an inhibition of
      the apoptotic pathway. Cultures treated with AraC had a decrease in the total
      number of GABAergic neurons and an increase in apoptotic cells as measured with
      the apoptotic marker cleaved caspase-3. Co-treatment with CRF rescued many
      GABAergic neurons. It is interesting to note that apoptotic cells do not exhibit
      GABA or c-fos positive immunolabeling. Thus, these data support the concept that
      CRF plays a neuroprotective role in the survival of GABAergic cerebellar neurons
      in culture after exposure to a neurotoxin.

PMID- 15246699
TI  - Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats.
AB  - Edaravone has an inhibitory effect on lipid peroxidation by scavenging free
      radicals and prevents vascular endothelial cell injury. We examined whether
      edaravone was effective on hypoxic-ischemic (HI) brain injury in immature brain
      or not using the Rice-Vannucci model. The initial dose, 3 mg/kg (0.05 ml) of
      edaravone, was injected intraperitoneally just before hypoxic exposure.
      Subsequently, the same dose was injected every 12 h until the animals were
      killed. Controls received saline injection as the same protocol. Macroscopic
      evaluation of brain injury revealed that the neuroprotective effect of edaravone
      on HI brain after 48 h post HI. TUNEL showed that edaravone injection decreased
      neurodegeneration. Quantitative analysis of cell death using H&E-stained 2.5
      microm sections showed that there was a trend for both necrotic and apoptotic
      cells to decrease in edaravone injection group. Edaravone injection inhibited the
      release of cytochrome c from mitochondria to cytosol and caspase-3 activation in
      cortex and hippocampus between 24 and 168 h post HI. Our results suggest that
      edaravone is protective after HI insult in the immature brain by decreasing both
      apoptosis and necrosis and also by inhibiting mitochondrial injury.

PMID- 15246700
TI  - Mitochondrial response to calcium in the developing brain.
AB  - Developmental differences in mitochondrial content and metabolic enzyme
      activities have been defined, but less is understood about the responses of brain
      mitochondria to stressful stimuli during development. Cerebral mitochondrial
      response to high Ca(2+) loads after brain injury is a critical determinant of
      neuronal outcome. Brain mitochondria isolated from 16-18-day-old rats had lower
      maximal, respiration-dependent Ca(2+) uptake capacity than brain mitochondria
      isolated from adult rats in the presence of ATP at both a pH of 7.0 and 6.5.
      However, in the absence of ATP, immature brain mitochondria exhibited greater
      Ca(2+) uptake capacity at pH 7.0 and 6.5, indicating a greater resistance of
      immature brain mitochondria to Ca(2+)-induced dysfunction under conditions
      relevant to those that exist during acute ischemic and traumatic brain injury.
      Acidosis reduced the maximal Ca(2+) uptake capacity in both immature and adult
      brain mitochondria. Cytochrome c was released from both immature and adult brain
      mitochondria in response to Ca(2+) exposure, but was not affected by cyclosporin
      A, an inhibitor of the mitochondrial membrane permeability transition.
      Developmental changes in mitochondrial response to Ca(2+) loads may have
      important implications in the pathobiology of brain injury to the developing
      brain.

PMID- 15246701
TI  - Differential effects of gestational buprenorphine, naloxone, and methadone on
      mesolimbic mu opioid and ORL1 receptor G protein coupling.
AB  - In addition to its use for heroin addiction pharmacotherapy in general,
      buprenorphine has advantages in treating maternal heroin abuse. To examine the
      gestational effects of buprenorphine on opioid receptor signaling, the [(35)S]
      GTP gamma S in situ binding induced by the mu agonist [D-Ala(2),MePhe(4),Gly(5)
      ol] enkephalin (DAMGO) or the nociceptin/orphanin FQ (N/OFQ) agonist was measured
      in mesolimbic structures of pup brains from pregnant rats administered with
      buprenorphine +/- naloxone, naloxone, or methadone by osmotic minipump. Drug- and
      gender-based changes in DAMGO- and N/OFQ-induced GTP gamma S binding were
      discovered in mesolimbic regions of dam, P2, and P7 brains. Buprenorphine and/or
      methadone gestational treatment attenuated DAMGO-induced GTP gamma S binding in
      some dam and male P2 mesolimbic regions. Methadone diminished DAMGO-induced GTP
      gamma S binding in almost all monitored brain regions of the dam but had few
      effects on their N/OFQ-induced GTP gamma S binding. Naloxone used in combination
      with buprenorphine blocked the inhibition by buprenorphine alone on DAMGO-induced
      GTP gamma S binding. In contrast to its inhibitory effects on DAMGO-induced GTP
      gamma S binding, buprenorphine stimulated N/OFQ-induced GTP gamma S binding in
      male P2 nucleus accumbens and lateral septum. Brain region-dependent gender
      differences in DAMGO-induced GTP gamma S binding were seen in P2 pups, and males
      showed greater sensitivity to buprenorphine and methadone than females. Our
      findings on mu opioid receptor (MOR) GTP-binding regulatory protein (G protein)
      coupling and its gender dependency are consistent with our earlier studies on mu
      receptor binding adaptation induced by buprenorphine in dams and neonatal rats
      after in utero treatment regimens, and they extend the gestational effects of
      this opiate to mu and N/OFQ receptor functionality.

PMID- 15246702
TI  - Evidence of newly generated neurons in the human olfactory bulb.
AB  - The subventricular zone (SVZ) is known to be the major source of neural stem
      cells in the adult brain. In rodents and nonhuman primates, many neuroblasts
      generated in the SVZ migrate in chains along the rostral migratory stream (RMS)
      to populate the olfactory bulb (OB) with new granular and periglomerular
      interneurons. In order to know if such a phenomenon exists in the adult human
      brain, we applied single and double immunostaining procedures to olfactory bulbs
      obtained following brain necropsy in normal adult human subjects. Double
      immunofluorescence labelling with a confocal microscope served to visualize cells
      that express markers of proliferation and immature neuronal state as well as
      markers that are specific to olfactory interneurons. Newborn cells that express
      cell cycle proteins [Ki-67, proliferating cell nuclear antigen (PCNA)] were
      detected in the granular and glomerular layers (GLs) of the human olfactory bulb;
      these cells coexpressed markers of immature neuronal state, such as Doublecortin
      (DCX), NeuroD and Nestin. Numerous differentiating cells expressed molecular
      markers of early committed neurons [beta-tubulin class III (TuJ1)] and were also
      immunoreactive for glutamic acid decarboxylase (GAD), a marker of GABAergic
      neurons, or tyrosine hydroxylase (TH), a marker of dopaminergic neurons. Other
      early committed neurons expressed the calcium-binding proteins calretinin (CR) or
      parvalbumin (PV). These results provide strong evidence for the existence of
      adult neurogenesis in the human olfactory system. Despite its relatively small
      size compared to that in rodents and nonhuman primates, the olfactory bulb in
      humans appears to be populated, throughout life, by new granular and
      periglomerular neurons that express a wide variety of chemical phenotypes.

PMID- 15246703
TI  - Pituitary adenylate cyclase-activating polypeptide in the brain, spinal cord and
      sensory organs of the zebrafish, Danio rerio, during development.
AB  - The distribution of Pituitary adenylate cyclase-activating polypeptide (PACAP)
      was investigated in the brain, pituitary and sensory organs of the zebrafish,
      Danio rerio, during development, in juvenile and adult specimens, using the
      immunofluorescence method. In 24 h post fertilization (hpf) embryos, PACAP
      immunoreactive cells appeared in the rostral telencephalon, dorsal diencephalon,
      caudal and medial rhombencephalon, spinal cord and retina. At 48 hpf stage,
      positive cells were present in the dorsal diencephalon, medial rhombencephalon,
      spinal cord, retina and olfactory placode (Op). At 72 hpf stage, additional
      immunoreactive elements appeared in the medial telencephalon, hypothalamus,
      mesencephalic tegmentum, retina and otic sensory epithelium (Ose). At day 5, new
      immunoreactive cells were found in the anterior rhombencephalon and pituitary
      pars distalis. At day 13, positive cells were mainly concentrated in the
      mesencephalic tegmentum and spinal cord. In the telencephalon, diencephalon,
      rhombencephalon and pituitary, the distribution of positive cells was similar to
      that previously reported. At 1 month stage, positive cells were detected in the
      hypothalamus, nucleus of the medial longitudinal fascicle (nMlf), rhombencephalic
      griseum centrale (Gc) and pituitary pars distalis. At 2-3 month stages,
      immunoreactive elements were found in several hypothalamic nuclei, in the
      mesencephalic nucleus isthmi, cerebellum and pituitary. In adults, PACAP
      immunoreactivity was confined to a few brain regions and the pituitary. PACAP
      immunoreactivity was transiently expressed in several regions suggesting that the
      peptide may have a role in the control of cells differentiation and proliferation
      during zebrafish ontogeny. The finding of positive fibers in the pituitary from
      day 5 onward indicates that PACAP may function from this stage as a
      hypophysiotropic peptide.

PMID- 15246704
TI  - Sex-specific development of cortical monoamine levels in mouse.
AB  - Several mental health disorders exhibit sex differences in monoamine levels
      associated with dimorphic cortical ontogeny. Studies in rodents support the
      notion that monoamines can profoundly modulate morphogenesis. Here, we show
      significant sex and hemisphere differences in BALB/cByJ mice on postnatal day 3
      for dopamine (DA) and serotonin (5-TH), supporting the notion that sex
      differences in early monoaminergic ontogeny may result in dimorphic cortical
      development. Such sex differences may also influence differential behavioral
      and/or clinical outcomes.

PMID- 15246705
TI  - Timing and location of rhodopsin expression in newly born rod photoreceptors in
      the adult teleost retina.
AB  - Labeling of newly divided retinal cells with bromodeoxyuridine (BrdU) and a
      rhodopsin mRNA probe revealed that rhodopsin is first expressed by new rod
      photoreceptors 2 days after cell birth in an adult cichlid fish. Most new cells
      that expressed rhodopsin had nuclei located in the vitreal half of the outer
      nuclear layer (ONL), lending further support to the hypothesis that movement from
      scleral to vitreal ONL is associated with rod differentiation.

PMID- 15246706
TI  - Expression of growth differentiation factor-5 in the developing and adult rat
      brain.
AB  - Expression of the dopaminergic neurotrophin GDF-5 in developing rat ventral
      mesencephalon (VM) was found to begin at embryonic day (E) 12 and peak on E14,
      when dopaminergic neurones undergo terminal differentiation. In the adult rat,
      GDF-5 was found to be restricted to heart and brain, being expressed in many
      areas of the brain, including striatum and midbrain. This indicates a role for
      GDF-5 in the development and maintenance of dopaminergic neurones.

PMID- 15246707
TI  - Neural and hormonal consequences of neonatal 5,7-dihydroxytryptamine may not be
      associated with serotonin depletion.
AB  - The neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) is often used in neonatal rats
      to induce specific, rapid, and permanent depletion of brain serotonin (5-HT). One
      assumed benefit of using this drug in neonates is that it is well-tolerated, with
      pups exhibiting few side effects normally attributed to 5-HT depletion. Here, we
      present evidence that 5,7-DHT administered neonatally induces seizure-like
      behavior, decreases weight gain, and increases plasma corticosterone without
      depletion of brain 5-HT.

PMID- 15246708
TI  - It is time for scientists to make the case for stem-cell research.

PMID- 15246709
TI  - Does Washington really know best?

PMID- 15246710
TI  - Clinical challenges in providing embryos for stem-cell initiatives.

PMID- 15246711
TI  - Justice, ethnicity, and stem-cell banks.

PMID- 15246712
TI  - Searching for reputability: first randomised study on bone-marrow transplantation
      in the heart.

PMID- 15246713
TI  - Smarter rather than stronger treatment of haematological malignancies and non
      malignant indications for stem-cell transplantation.

PMID- 15246714
TI  - Scientific freedom and research cloning: can a ban be justified?

PMID- 15246715
TI  - Fellowship of the rings.

PMID- 15246716
TI  - Assessment of NICE guidance.

PMID- 15246717
TI  - Safety and efficacy of rosuvastatin.

PMID- 15246718
TI  - Assessment of NICE guidance.

PMID- 15246719
TI  - Assessment of NICE guidance.

PMID- 15246721
TI  - Simian retroviral infections in human beings.

PMID- 15246722
TI  - Simian retroviral infections in human beings.

PMID- 15246724
TI  - Reversing the obesity epidemic.

PMID- 15246725
TI  - Occupational health and safety proposals.

PMID- 15246726
TI  - Intracoronary autologous bone-marrow cell transfer after myocardial infarction:
      the BOOST randomised controlled clinical trial.
AB  - BACKGROUND: Emerging evidence suggests that stem cells and progenitor cells
      derived from bone marrow can be used to improve cardiac function in patients
      after acute myocardial infarction. In this randomised trial, we aimed to assess
      whether intracoronary transfer of autologous bone-marrow cells could improve
      global left-ventricular ejection fraction (LVEF) at 6 months' follow-up. METHODS:
      After successful percutaneous coronary intervention (PCI) for acute ST-segment
      elevation myocardial infarction, 60 patients were randomly assigned to either a
      control group (n=30) that received optimum postinfarction medical treatment, or a
      bone-marrow-cell group (n=30) that received optimum medical treatment and
      intracoronary transfer of autologous bone-marrow cells 4.8 days (SD 1.3) after
      PCI. Primary endpoint was global left-ventricular ejection fraction (LVEF) change
      from baseline to 6 months' follow-up, as determined by cardiac MRI. Image
      analyses were done by two investigators blinded for treatment assignment.
      Analysis was per protocol. FINDINGS: Global LVEF at baseline (determined 3.5 days
      [SD 1.5] after PCI) was 51.3 (9.3%) in controls and 50.0 (10.0%) in the bone
      marrow cell group (p=0.59). After 6 months, mean global LVEF had increased by 0.7
      percentage points in the control group and 6.7 percentage points in the bone
      marrow-cell group (p=0.0026). Transfer of bone-marrow cells enhanced left
      ventricular systolic function primarily in myocardial segments adjacent to the
      infarcted area. Cell transfer did not increase the risk of adverse clinical
      events, in-stent restenosis, or proarrhythmic effects. INTERPRETATION:
      Intracoronary transfer of autologous bone-marrow-cells promotes improvement of
      left-ventricular systolic function in patients after acute myocardial infarction.

PMID- 15246727
TI  - Investigation of multipotent postnatal stem cells from human periodontal
      ligament.
AB  - BACKGROUND: Periodontal diseases that lead to the destruction of periodontal
      tissues--including periodontal ligament (PDL), cementum, and bone--are a major
      cause of tooth loss in adults and are a substantial public-health burden
      worldwide. PDL is a specialised connective tissue that connects cementum and
      alveolar bone to maintain and support teeth in situ and preserve tissue
      homoeostasis. We investigated the notion that human PDL contains stem cells that
      could be used to regenerate periodontal tissue. METHODS: PDL tissue was obtained
      from 25 surgically extracted human third molars and used to isolate PDL stem
      cells (PDLSCs) by single-colony selection and magnetic activated cell sorting.
      Immunohistochemical staining, RT-PCR, and northern and western blot analyses were
      used to identify putative stem-cell markers. Human PDLSCs were transplanted into
      immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue
      regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal
      stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions,
      PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen
      forming cells. When transplanted into immunocompromised rodents, PDLSCs showed
      the capacity to generate a cementum/PDL-like structure and contribute to
      periodontal tissue repair. INTERPRETATION: Our findings suggest that PDL contains
      stem cells that have the potential to generate cementum/PDL-like tissue in vivo.
      Transplantation of these cells, which can be obtained from an easily accessible
      tissue resource and expanded ex vivo, might hold promise as a therapeutic
      approach for reconstruction of tissues destroyed by periodontal diseases.

PMID- 15246728
TI  - Reduced intensity haemopoietic stem-cell transplantation for treatment of non
      malignant diseases in children.
AB  - BACKGROUND: Transplantation of allogeneic haemopoietic stem cells can cure
      several non-malignant disorders in children. Transplantation with reduced
      intensity preparation might achieve the same goals but with less toxicity. We
      undertook a pilot study to determine engraftment rates, kinetics of engraftment,
      toxicity, and acute graft-versus-host disease (GVHD) associated with a uniform
      reduced intensity haemopoietic stem-cell transplant (HSCT) regimen for children
      with non-malignant diseases. METHODS: We studied 13 paediatric patients with non
      malignant disorders who underwent reduced intensity HSCT at Children's Memorial
      Hospital from January, 2000, to February, 2004. Stem-cell sources included
      unrelated donor, matched-sibling peripheral blood stem cells, and unrelated cord
      blood. A uniform preparative regimen was used, consisting of fludarabine,
      busulfan, and anti-thymocyte globulin. Major endpoints were engraftment,
      transplant-related mortality at day 100, short-term toxicities, and incidence of
      acute GVHD. RESULTS: 72% of evaluable patients achieved full donor engraftment.
      There was rapid reconstitution of platelets (median 13.5 days) and neutrophils
      (median 18 days). Short-term toxicities were minimal, as seen by a median length
      of hospital stay of 7 days (between days 0-100). Incidence of grade II-IV acute
      GVHD was 8%. Two patients died before day 100 from underlying disease and viral
      infection, respectively (day 100 transplant-related mortality of 15%). The 1-year
      overall survival was 84% (95% CI 64-100). Most patients with immunodeficiencies
      and metabolic disorders had excellent donor engraftment and disease resolution or
      stabilisation, but most of those with haemoglobinopathies rejected their graft.
      INTERPRETATION: This reduced intensity regimen followed by HSCT provides a good
      alternative to myeloablative HSCT for children with non-malignant disorders,
      except for haemoglobinopathies, in which engraftment is poor. Even patients with
      unrelated donor haemopoietic stem-cell transplants had adequate engraftment with
      acceptable toxicities.

PMID- 15246729
TI  - Functional antigen-presenting leucocytes derived from human embryonic stem cells
      in vitro.
AB  - BACKGROUND: Differentiated cells derived from pluripotent human embryonic stem
      (hES) cells offer the opportunity for new transplantation therapies. However, hES
      cells and their differentiated progeny express highly polymorphic MHC molecules
      that serve as major graft rejection antigens to the immune system of allogeneic
      hosts. To achieve sustained engraftment of donor cells, strategies must be
      developed to overcome graft rejection without broadly suppressing host immunity.
      One approach entails induction of donor-specific immune tolerance by establishing
      chimeric engraftment in hosts with haemopoietic cells derived from an existing
      hES cell line. We aimed to develop methods to efficiently differentiate hES cells
      to haemopoietic cells, including immune-modulating leucocytes, a prerequisite of
      the tolerance induction strategies applying to hES cell-mediated transplantation.
      METHODS: We developed a method to generate a broad range of haemopoietic cells
      from hES-generated embryonic bodies in the absence of murine stromal feeder
      cells. Embryonic bodies were further cultured in the presence of haemopoietic
      cytokines. In addition to flow cytometric analyses of haemopoietic cell markers,
      we analysed the hES cell-derived haemopoietic cells by colony-forming assays (for
      erythroid and myeloid progenitor cells), cytochemical staining, and mixed
      leucocyte reactions to determine the functional capacity of the generated antigen
      presenting cells. FINDINGS: 12 independent experiments were done. When selected
      growth factors were added, leucocytes expressing CD45 were generated and released
      into culture media for 6-7 weeks. Under the condition used, both erythroid and
      myeloid progenitor cells were generated. About 25% of the generated leucocytes
      acquired MHC class II and costimulatory molecule expression. These hES-derived,
      MHC class II+ leucocytes resembled dendritic cells and macrophages, and they
      functioned as antigen-presenting cells capable of eliciting allogeneic CD4 and
      CD8 T-cell responses in culture. INTERPRETATION: The hES cell-derived antigen
      presenting cells could be used to regulate alloreactive T cells and induce immune
      tolerance for improvement of the transplant acceptance of hES-cell derivatives.

PMID- 15246730
TI  - Efficient generation of neural precursors from adult human skin: astrocytes
      promote neurogenesis from skin-derived stem cells.
AB  - BACKGROUND: Neural stem cells are a potential source of cells for drug screening
      or cell-based treatments for neurodegenerative diseases. However, ethical and
      practical considerations limit the availability of neural stem cells derived from
      human embryonic tissue. An alternative source of human neural stem cells is
      needed; a source that is readily accessible, easily expanded, and reliably
      induced to a neural fate. METHODS: Dermis isolated from biopsy samples of adult
      human skin was cultured and expanded in the presence of the mitogens epidermal
      growth factor (EGF) and fibroblast growth factor 2 (FGF 2), and then by serum. We
      used immunocytochemical techniques, clonal analysis, and physiological
      characterisation to assess neural differentiation after the treatment of expanded
      cells with novel induction media. FINDINGS: Initial characterisation of skin
      samples confirmed the absence of nestin, a neural precursor marker. Sequential
      culture in EGF and FGF 2 followed by adherent expansion in serum, and re-exposure
      to mitogens in substrate-free conditions resulted in large numbers of nestin
      positive/musashi-positive neural precursors. Subsequent exposure of these
      precursors to hippocampal-astrocyte-derived signals resulted in cells of neuronal
      morphology that had stable expression of markers of neuronal differentiation
      (neurofilament, beta tubulin). We also show the presence of voltage-dependent
      calcium transients, and demonstrate monoclonal neural potential. INTERPRETATION:
      We describe the isolation and characterisation of cells derived from adult human
      dermis that can be expanded for extended periods of time in vitro, while
      retaining inducible neural potential. The generation of almost limitless numbers
      of neural precursors from a readily accessible autologous adult human source
      provides a platform for further experimental studies and has potential
      therapeutic implications.

PMID- 15246732
TI  - Stem cells and repair of the heart.
AB  - Stem-cell therapy provides the prospect of an exciting and powerful treatment to
      repair the heart. Although research has been undertaken in animals to analyse the
      safety and efficacy of this new approach, results have been inconclusive. The
      mechanism by which stem cells could improve cardiac function remains unclear. We
      describe the background to the concept of natural repair and the work that has
      been done to establish the role of stem cells in cardiac repair. Controversies
      have arisen in interpretation of experimental data. The important issues
      surrounding the application of stem-cell therapy to man are discussed critically.
      We discuss the future of this pioneering work in the setting of growing concerns
      about clinical studies in man without understanding the biological mechanisms
      involved, with the difficulties in funding this type of research.

PMID- 15246731
TI  - Microchimerism in female bone marrow and bone decades after fetal mesenchymal
      stem-cell trafficking in pregnancy.
AB  - Fetal cells enter maternal blood during pregnancy and persist in women with
      autoimmune disease. The frequency of subsequent fetomaternal microchimerism in
      healthy women and its cell type is unknown. To test the hypothesis that fetal
      mesenchymal stem cells persist in maternal organs, we studied female bone marrow
      and ribs. Male cells were identified by XY fluorescence in-situ hybridisation in
      marrow-derived mesenchymal stem cells and in rib sections from all women with
      male pregnancies, but not in controls (9/9 vs 0/5, p=0.0005). We conclude that
      fetal stem cells transferred into maternal blood engraft in marrow, where they
      remain throughout life. This finding has implications for normal pregnancy, for
      obstetric complications that increase fetomaternal trafficking, and for graft
      survival after transplantation.

PMID- 15246733
TI  - Adult stem cells--reprogramming neurological repair?
AB  - Much excitement has surrounded recent breakthroughs in embryonic stem-cell
      research. Of lower profile, but no less exciting, are the advances in the field
      of adult stem-cell research, and their implications for cell therapy. Clinical
      experience from use of adult haemopoietic stem cells in haematology will
      facilitate and hasten transition from laboratory to clinic--indeed, clinical
      trials using adult human stem cells are already in progress in some disease
      states, including myocardial ischaemia. Here, with particular reference to
      neurology, we review processes that might underlie apparent changes in adult cell
      phenotype. We discuss implications these processes might have for the development
      of new therapeutic strategies using adult stem cells.

PMID- 15246734
TI  - Stem-cell therapy for amyotrophic lateral sclerosis.
AB  - CONTEXT: With the lack of effective drug treatments for amyotrophic lateral
      sclerosis (ALS), and compelling preclinical data, stem-cell research has
      highlighted this disease as a candidate for stem-cell treatment. Stem-cell
      transplantation is an attractive strategy for neurological diseases and early
      successes in animal models of neurodegnerative disease generated optimism about
      restoring function or delaying degeneration in human beings. The restricted
      potential of adult stem cells has been challenged over the past 5 years by
      reports on their ability to acquire new unexpected fates beyond their embryonic
      lineage (transdifferentiation). Therefore, autologous or allogeneic stem cells,
      undifferentiated or transdifferentiated and manipulated epigenetically or
      genetically, could be a candidate source for local or systemic cell-therapies in
      ALS. STARTING POINT: Albert Clement and colleagues (Science 2003; 302: 113-17)
      showed that in SOD1G93A chimeric mice, motorneuron degeneration requires damage
      from mutant SOD1 acting in non-neuronal cells. Wild-type non-neuronal (glial)
      cells could delay degeneration and extend survival of mutant-expressing
      motorneurons. Letizia Mazzini and colleagues (Amyotroph Lateral Scler Other Motor
      Neuron Disord 2003; 4: 158-61) injected autologous bone-marrow-derived stem cells
      into the spinal cord of seven ALS patients. These investigators reported that the
      procedure had a reasonable margin of clinical safety. WHERE NEXT? The success of
      cell-replacement therapy in ALS will depend a lot on preclinical evidence,
      because of the complexity and precision of the pattern of connectivity that needs
      to be restored in degenerating motoneurons. Stem-cell therapy will need to be
      used with other drugs or treatments, such as antioxidants and/or infusion of
      trophic molecules.

PMID- 15246735
TI  - Stem-cell therapy for diabetes mellitus.
AB  - CONTEXT: Curative therapy for diabetes mellitus mainly implies replacement of
      functional insulin-producing pancreatic beta cells, with pancreas or islet-cell
      transplants. However, shortage of donor organs spurs research into alternative
      means of generating beta cells from islet expansion, encapsulated islet
      xenografts, human islet cell-lines, and stem cells. Stem-cell therapy here
      implies the replacement of diseased or lost cells from progeny of pluripotent or
      multipotent cells. Both embryonic stem cells (derived from the inner cell mass of
      a blastocyst) and adult stem cells (found in the postnatal organism) have been
      used to generate surrogate beta cells or otherwise restore beta-cell functioning.
      STARTING POINT: Recently, Andreas Lechner and colleagues failed to see
      transdifferentiation into pancreatic beta cells after transplantation of bone
      marrow cells into mice (Diabetes 2004; 53: 616-23). Last year, Jayaraj Rajagopal
      and colleagues failed to derive beta cells from embryonic stem cells (Science
      2003; 299: 363). However, others have seen such effects. WHERE NEXT? As in every
      emerging field in biology, early reports seem confusing and conflicting.
      Embryonic and adult stem cells are potential sources for beta-cell replacement
      and merit further scientific investigation. Discrepancies between different
      results need to be reconciled. Fundamental processes in determining the
      differentiation pathways of stem cells remain to be elucidated, so that rigorous
      and reliable differentiation protocols can be established. Encouraging studies in
      rodent models may ultimately set the stage for large-animal studies and
      translational investigation.

PMID- 15246736
TI  - Stem-cell consequences of embryo epigenetic defects.
AB  - CONTEXT: The genetic code in the DNA of virtually every somatic cell can produce
      the entire complement of encoded proteins. Acetylation of histones and
      methylation of histones and DNA cytosine residues are part of the complex
      epigenetic regulatory process determining lineage-specific gene expression by
      altering the local structure of chromatin. After fertilisation, sperm DNA
      exchanges protamines for histones recruited from oocyte cytoplasm, reconfiguring
      both parental genomes into an epigenetic state conducive to activating the
      embryonic developmental programme. The identification of epigenetic reprogramming
      mechanisms is a major interest, rekindled by the ability of at least some somatic
      cells to acquire totipotency after somatic-cell nuclear transfer. STARTING POINT:
      Recently, Woo SukHwang and colleagues (Science 2004; 303: 1669-74) derived a
      human embryonic stem-cell line from embryo therapeutic cloning. Chad Cowan and
      colleagues (N Engl JMed 2004; 350: 1353-56) produced 17 new lines from embryos
      supernumerary to infertility treatments. However, increasing evidence from a
      range of mammals shows a propensity for epigenetic errors with embryo
      technologies. If paralleled in human embryos, the effect on tumorigenic and
      differentiation properties of embryonic stem cells needs to be established. WHERE
      NEXT? Identifying the mechanisms in the oocyte that reprogramme a somatic cell to
      the embryonic state might allow somatic cells to be reprogrammed ex ovo by in
      vitro manipulation of the epigenome. Because the oocyte is designed to
      reprogramme the sperm genome, which is in a different chromatin state from a
      somatic cell, perhaps many of the epigenetic errors induced by somatic-cell
      nuclear transfer could be avoided by a more targeted approach.

PMID- 15246737
TI  - International policy failures: cloning and stem-cell research.
AB  - In late 2003, two international bodies were unable to resolve disagreements that
      involved bioethical issues. First, the United Nations General Assembly failed to
      pass a treaty on reproductive cloning because of insistence by some countries
      that the treaty include a ban on cloning for research. In view of the importance
      of enacting prohibition of reproductive cloning, the two issues should be
      separated and each argued on its own merits. Relevant objections to separation of
      the two issues can be refuted. Second, the European Union (EU) failed to agree on
      conditions for funding stem-cell research because of the diversity of views and
      policies of the countries of the EU. Because a stalemate was reached, funding
      decisions in the next programme cycle will be made on an ad hoc basis. Scientists
      will not have information they need to plan research programmes, suggesting that
      clear guidelines, even if restrictive, are preferable to vague unpublicised
      criteria.

PMID- 15246738
TI  - Temporal restrictions and the impasse on human embryonic stem-cell research.

PMID- 15246739
TI  - Paralysis, Roman Reed, and a ban on stem-cell research.

PMID- 15246740
TI  - Granulomatous amoebic encephalitis.

PMID- 15246741
TI  - Retinoic acid receptor alpha expression and cutaneous ageing.
AB  - Intrinsic ageing of human skin is a subtle and gradual process that demonstrates
      few clinical or histological features until old age (>70 years). Initial work
      indicates that aged skin is "retinoid sensitive" but there is little data on the
      role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin
      ageing. As nuclear retinoid receptors have been implicated in ageing in rodents,
      we studied the distribution of these receptors in intrinsically aged as compared
      to young, photoprotected human skin. We found that intrinsic ageing of skin in
      vivo is accompanied by significant increases of RAR alpha mRNA and protein
      whereas other isoforms show no alteration with age. In vitro transfection of COS
      1 cells with the RAR alpha gene induces expression of matrix metalloproteinase-1
      (MMP-1), an enzyme known to play an active role in remodelling of the dermis in
      intrinsically aged and photoaged skin. Furthermore, addition of all-trans
      retinoic acid (RA) to cultures of RAR alpha-transfected COS-1 cells diminishes
      RAR alpha and returns levels of MMP-1 to those approaching baseline. These
      results demonstrate that intrinsic ageing of human skin is accompanied by
      significant elevation in the content of RAR alpha and that over-expression of RAR
      alpha influences expression of MMP-1, an important mediator of skin ageing.

PMID- 15246742
TI  - Ontogenetic profile of glutamate uptake in brain structures slices from rats:
      sensitivity to guanosine.
AB  - The excitotoxicity of the neurotransmitter glutamate has been shown to be
      connected with many acute and chronic diseases of the CNS. High affinity sodium
      dependent glutamate transporters play a key role in maintaining adequate levels
      of extracellular glutamate. In the present study, we used slices of striatum,
      hippocampus and cortex from rat brain to describe the in vitro profile of
      glutamate uptake during development and ageing, and its sensitivity to guanosine.
      In all structures, glutamate uptake was higher in immature animals. There was a
      maximum decrease in glutamate uptake in striatum and hippocampus in 15-month-old
      rats, which later increased, while in cortex there was a significant decrease in
      rats aged 60 days old. The effect of guanosine seems to be age and structure
      dependent since the increase in basal glutamate uptake was only seen in slices of
      cortex from 10-day-old animals.

PMID- 15246743
TI  - Protective effect of retinoic acid on interleukin-1 beta-induced cytotoxicity of
      pancreatic beta-cells.
AB  - Cytokines produced by immune cells in pancreatic islets infiltrating are
      important mediators of beta-cell destruction in insulin-dependent diabetes
      mellitus. In this study, the effects of retinoic acid (RA) on cytokine-induced
      beta-cell dysfunction were examined. RA significantly protected interleukin-1
      beta (IL-1) and interferon-gamma (IFN-gamma)-mediated cytotoxicity of rat
      insulinoma cell (RINm5F), and also reduced in IL-1 and IFN-gamma-induced nitric
      oxide (NO) production, which correlated well with reduced levels of the inducible
      form of NO synthase (iNOS) mRNA and protein. The molecular mechanism, by which RA
      inhibited iNOS gene expression, appeared to involve the inhibition of NF-kappa B
      activation. Our results suggest possible therapeutic value of RA for the
      prevention of diabetes mellitus progression.

PMID- 15246744
TI  - Werner syndrome protein 1367 variants and disposition towards coronary artery
      disease in Caucasian patients.
AB  - The leading causes of death for individuals with Werner syndrome (WS) are
      myocardial infarction (MI) and stroke. The WS gene encodes a nuclear protein with
      both helicase and exonuclease activities. While individuals with WS have
      mutations that result in truncated, inactive proteins, several sequence variants
      have been described in apparently unaffected individuals. Some of these gene
      polymorphisms encode non-conservative amino acid substitutions, and it is
      expected that the changes would affect enzyme activity, although this has not
      been determined. Two research groups have studied the Cys/Arg 1367 polymorphism
      (located near the nuclear localization signal) in healthy and MI patients. Their
      results suggest that the Arg allele is protective against MI. We have
      characterized the Cys (C) and Arg (R) forms of the protein and find no notable
      difference in helicase and nuclease activities, or in nuclear/cytoplasmic
      distribution. The frequency of the C/R alleles in healthy individuals and
      subjects with coronary artery disease (CAD) drawn from the Baltimore Longitudinal
      Study of Aging (BLSA) was also examined. There was no indication that the R
      allele was protective against CAD. We conclude that the C/R polymorphism does not
      affect enzyme function or localization and does not influence CAD incidence in
      the BLSA cohort.

PMID- 15246745
TI  - Insulin-like growth factor-I (IGF-I) and its association with lymphocyte
      homeostasis in the ageing cat.
AB  - Ageing affects feline lymphocyte homeostasis in a similar pattern to that
      observed in other long-lived mammalian species, contributing to increased levels
      of morbidity and mortality in the ageing cat. Insulin-like growth factor-I (IGF
      I) is now recognised as an important endocrine regulator of immunity and has been
      shown to decline with age in humans and rodent species. Analysis of plasma IGF-I
      in adult and senior cats confirmed that the older cats had significantly lower
      circulating levels of IGF-I. In order to determine whether an association existed
      between lymphocyte subpopulations and IGF-I levels in the cat, each parameter was
      measured and subjected to regression analysis. A highly significant association
      was found in vivo between plasma IGF-I and CD4(+) T-cell values in the senior
      group, but no such association was observed in the adult group. In order that
      this relationship could be examined further, in vitro studies were undertaken to
      investigate the effects of physiologically relevant concentrations of recombinant
      human IGF-I (rhIGF-l) on peripheral blood lymphocyte (PBL) cultures from adult
      and senior cats. While rhlGF-I induced low-level thymidine incorporation in the
      lymphocytes isolated from the senior group, it did not enhance the proliferative
      response to T-cell mitogens, Con A and PHA in either group, nor did it rescue
      cells from oxidatively induced apoptosis. Furthermore, the proliferative response
      of PBL from seniors did not attain the magnitude of that from the adults at any
      concentration of rhIGF-l. We propose that the observed association is not a
      direct effect of IGF-I on PBL, but may be mediated through an effect of IGF-I on
      the thymus.

PMID- 15246746
TI  - L-carnitine and DL-alpha-lipoic acid reverse the age-related deficit in
      glutathione redox state in skeletal muscle and heart tissues.
AB  - In the present study, the glutathione redox system was evaluated as a function of
      age in rat heart and muscle. A decline in reduced glutathione (GSH) levels is
      associated with aging and many age-related diseases. The objective of this study
      was to determine whether L-carnitine and DL-alpha-lipoic acid could compensate
      for GSH depletion in protection against oxidative insults. In this study we
      determined reduced glutathione, oxidized glutathione (GSSG), glutathione
      peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate
      dehydrogenase (G6PDH) in skeletal muscle and heart of young and aged rats. We
      also calculated GSH/GSSG molar ratio and glutathione redox system. GSH levels
      were significantly lowered in aged rats than young rats. Conversely, GSSG levels
      were significantly high in aged rats. GSH/GSSG molar ratio and redox index were
      found to decreased in aged rats. The activities of GPx, GR, and G6PDH were found
      to be decreased in aged rats when compared with young rats. Supplementation of
      carnitine and lipoic acid to aged rats significantly increased the GSH levels
      thereby increasing the activity of GPx, GR, and G6PDH in skeletal muscle and
      heart of aged rats. In conclusion, our study suggests that supplementation of
      carnitine and lipoic acid to aged rats improves the glutathione redox system.

PMID- 15246747
TI  - Growth-associated proteins and regeneration-induced gene expression in the aging
      neuron.
AB  - Axonal elongation and sprouting during regeneration are retarded with aging but
      the etiology of this is unclear. We investigated whether this age-associated
      decline is related to a decline in expression of three different growth
      associated proteins (GAPs): alpha(1)-tubulin, neurofilament (NF) light subunit
      (NF-L) and GAP-43. Northern analysis was performed on L4-L5 dorsal root ganglia
      (DRG) of young (3 months) and aged (23 months) rats following a sciatic nerve
      crush and compared to their age-matched controls. The results show that initial
      mRNA levels of alpha(1)-tubulin and NF-L in the control aged rat DRG were half
      those of the control young adults, whereas expression of GAP-43 was unchanged.
      Two weeks after axotomy, the expression of alpha(1)-tubulin and GAP-43 in the
      aged DRG was induced to the same levels as in the axotomized young adult, and the
      expression of NF-L decreased proportionately in both age groups. These results
      indicate that certain neuronal mRNAs, such as alpha(1)-tubulin and NF-L may be
      maintained at lower levels in aging DRG neurons, whereas others, such as GAP-43
      appear to be unaltered. However, during regeneration, the aging DRG neuron
      appears capable of inducing alpha(1)-tubulin, NF-L and GAP-43 as well as the
      young adult.

PMID- 15246748
TI  - Changes with age in the distribution of a frailty index.
AB  - Models of human mortality include a factor that summarises intrinsic differences
      in individual rates of ageing, commonly called frailty. Frailty also describes a
      clinical syndrome of apparent vulnerability. In a representative, cross
      sectional, Canadian survey (n = 66,589) we calculated a frailty index as the mean
      accumulation of deficits and previously showed it to increase exponentially with
      age. Here, its density function exhibited a monotonic change in shape, being
      least skewed at the oldest ages. Although the shape gradually changed, the
      frailty index was well fitted by a gamma distribution. Of note, the variation
      coefficient, initially high, decreased from middle age on. Being able to quantify
      frailty means that health risks can be summarised at both the individual and
      group levels.

PMID- 15246749
TI  - Low contrast vision function predicts subsequent acuity loss in an aged
      population: the SKI study.
AB  - Can vision tests predict subsequent loss of acuity? The association between
      performance on several low contrast spatial vision measures, glare recovery,
      color discrimination, flicker sensitivity, stereopsis and ocular disease status
      at baseline and acuity loss 4.4 years later was examined in a large aged random
      sample with good initial acuity. In univariate analyses, several vision measures,
      retinal disease status and age were each significant predictors of subsequent
      acuity loss. In a multiple regression analysis, only low contrast spatial vision
      was a significant predictor, but the other vision measures, retinal disease
      status and age were not. For each doubling of low contrast spatial vision
      threshold at baseline, individuals were more than two times as likely to suffer
      subsequent significant visual acuity loss. Tests of low contrast spatial vision
      are strong predictors of significant subsequent visual acuity loss. These
      findings have implications for clinical trials, clinical management, and
      acceptance of these measures into clinical practice.

PMID- 15246750
TI  - Polarizational colours could help polarization-dependent colour vision systems to
      discriminate between shiny and matt surfaces, but cannot unambiguously code
      surface orientation.
AB  - It was hypothesized that egg-laying Papilio butterflies could use polarizational
      colours as a cue to detect leaf orientation and to discriminate between shiny and
      matt leaves. These hypotheses would be supported if the following general
      questions were answered positively: (1) Can surface orientation be unambiguously
      coded by the polarizational colours perceived by polarization-sensitive colour
      vision systems? (2) Are the changes in the polarizational colours due to retinal
      rotation significantly different between shiny and matt surfaces? Using video
      polarimetry, we measured the reflection-polarizational characteristics of a shiny
      green hemisphere in the red, green and blue spectral ranges for different solar
      elevations and directions of view with respect to the solar azimuth as well as
      for sunlit and shady circumstances under clear skies. The continuously curving
      hemisphere models numerous differently oriented surfaces. Using the polarization-
      and colour-sensitive retina model developed earlier, we computed the
      polarizational colours of the hemisphere, and investigated the correlation
      between colours and local surface orientation. We also calculated the maximal
      changes of the polarizational colours of shiny and matt hemispheres induced by
      rotation of the retina. We found that a surface with any orientation can possess
      almost any polarizational colour under any illumination condition. Consequently,
      polarizational colours cannot unambiguously code surface orientation.
      Polarization sensitivity is even disadvantageous for the detection of surface
      orientation by means of colours. On the other hand, the colour changes due to
      retinal rotation can be significantly larger for shiny surfaces than for matt
      ones. Thus, polarizational colours could help discrimination between shiny and
      matt surfaces. The physical and perceptional reasons for these findings are
      explained in detail. Our results and conclusions are of general importance for
      polarization-dependent colour vision systems.

PMID- 15246751
TI  - Effects on orientation perception of manipulating the spatio-temporal prior
      probability of stimuli.
AB  - Spatial and temporal regularities commonly exist in natural visual scenes. The
      knowledge of the probability structure of these regularities is likely to be
      informative for an efficient visual system. Here we explored how manipulating the
      spatio-temporal prior probability of stimuli affects human orientation
      perception. Stimulus sequences comprised four collinear bars (predictors) which
      appeared successively towards the foveal region, followed by a target bar with
      the same or different orientation. Subjects' orientation perception of the foveal
      target was biased towards the orientation of the predictors when presented in a
      highly ordered and predictable sequence. The discrimination thresholds were
      significantly elevated in proportion to increasing prior probabilities of the
      predictors. Breaking this sequence, by randomising presentation order or
      presentation duration, decreased the thresholds. These psychophysical
      observations are consistent with a Bayesian model, suggesting that a predictable
      spatio-temporal stimulus structure and an increased probability of collinear
      trials are associated with the increasing prior expectation of collinear events.
      Our results suggest that statistical spatio-temporal stimulus regularities are
      effectively integrated by human visual cortex over a range of spatial and
      temporal positions, thereby systematically affecting perception.

PMID- 15246752
TI  - Slant or occlusion: global factors resolve stereoscopic ambiguity in sets of
      horizontal lines.
AB  - Perceived slant was measured for horizontal lines aligned on one side and of
      varying lengths whose length disparity was either a constant linear amount for
      all lines (consistent with uniocular occlusion) or proportional to line length
      (consistent with global slant). Although the disparity of any line was ambiguous
      with respect to these two possibilities, slant of individual lines did not occur
      in the former case, but a subjective contour in depth was reported along the
      alignment. For proportional disparity of the set, global slant was seen. Adding a
      constant length to each line on the invalid eye for occlusion resulted in
      multiple slants. Smooth uniocular variations in alignment shape elicited
      subjective contours slanting or curving in depth. Global context can disambiguate
      the depth status of individual disparate lines.

PMID- 15246753
TI  - An integrative model of binocular vision: a stereo model utilizing interocularly
      unpaired points produces both depth and binocular rivalry.
AB  - Half-occluded points (visible only in one eye) are perceived at a certain depth
      behind the occluding surface without binocular rivalry, even though no disparity
      is defined at such points. Here we propose a stereo model that reconstructs 3D
      structures not only from disparity information of interocularly paired points but
      also from unpaired points. Starting with an array of depth detection cells, we
      introduce cells that detect unpaired points visible only in the left eye or the
      right eye (left and right unpaired point detection cells). They interact
      cooperatively with each other based on optogeometrical constraints (such as
      uniqueness, cohesiveness, occlusion) to recover the depth and the border of 3D
      objects. Since it is contradictory for monocularly visible regions to be visible
      in both eyes, we introduce mutual inhibition between left and right unpaired
      point detection cells. When input images satisfy occlusion geometry, the model
      outputs the depth of unpaired points properly. An interesting finding is that
      when we input two unmatched images, the model shows an unstable output that
      alternates between interpretations of monocularly visible regions for the left
      and the right eyes, thereby reproducing binocular rivalry. The results suggest
      that binocular rivalry arises from the erroneous output of a stereo mechanism
      that estimates the depth of half-occluded unpaired points. In this sense, our
      model integrates stereopsis and binocular rivalry, which are usually treated
      separately, into a single framework of binocular vision. There are two general
      theories for what the "rivals" are during binocular rivalry: the two eyes, or
      representations of two stimulus patterns. We propose a new hypothesis that
      bridges these two conflicting hypotheses: interocular inhibition between
      representations of monocularly visible regions causes binocular rivalry. Unlike
      the traditional eye theory, the level of the interocular inhibition introduced
      here is after binocular convergence at the stage solving the correspondence
      problem, and thus open to pattern-specific mechanisms.

PMID- 15246754
TI  - Effect of adaptation direction on the motion VEP and perceived speed of drifting
      gratings.
AB  - The N200 amplitude of the motion-onset VEP evoked by a parafoveal grating of
      variable contrast (0.5-64%), constant speed (2 degrees/s), direction
      (horizontally rightward), and spatial frequency (2 cpd) was studied before and
      after adaptation to a stationary or drifting grating (1, 2, or 4 degrees/s
      rightward or leftward). These results are compared to those for the pattern
      appearance VEP. Psychophysical measurements were made simultaneously of the
      perceived speed. While iso-directional (rightward) adaptation leads to a mean
      amplitude reduction of 39%, the decrease after counter-directional adaptation has
      a size of 20%. The post-adaptation matches of perceived speed differ in
      dependence on the iso-directional adapting speed and decrease on average to 98%,
      85%, and 69% of the pre-adapt perceived speed after 1, 2, and 4 degrees/s
      adapting speeds, respectively. The perceived speed is moderately reduced (83% of
      the pre-adapt value) after counter-directional adaptation nearly independently of
      the adapting speed. A model of velocity processing is presented, which enables us
      to predict the trends of the experimental motion VEP and perceived speed data.

PMID- 15246755
TI  - The motion-induced position shift depends on the perceived direction of bistable
      quartet motion.
AB  - Motion can influence the perceived position of nearby stationary objects (Nature
      Neuroscience 3 (2000) 954). To investigate the influence of high-level motion
      processes on the position shift while controlling for low-level motion signals,
      we measured the position shift as a function of the motion seen in a bistable
      quartet. In this stimulus, motion can be seen along either one or the other of
      two possible paths. An illusory position shift was observed only when the flashes
      were adjacent to the path where motion was perceived. If the flash was adjacent
      to the other path, where no motion was perceived, there was no illusory
      displacement. Thus for the same physical stimulus, a change in the perceived
      motion path determined the location where illusory position shifts would be seen.
      This result indicates that high-level motion processes alone are sufficient to
      produce the position shift of stationary objects. The effect of the timing of the
      test flash between the onset and offset of the motion was also examined. The
      position shifts were greatest at the onset of motion, then decreasing gradually,
      disappearing at the offset of motion. We propose an attentional repulsion
      explanation for the shift effect.

PMID- 15246756
TI  - Wider recognition in peripheral vision common to different subtypes of dyslexia.
AB  - Italian children (n = 125) were classified into dyslexics, poor readers and
      ordinary readers. The dyslexics were further classified into the Boder and Bakker
      subtypes. The children were tested with the form-resolving field (FRF), which
      measures central and peripheral visual recognition. Dyslexics show higher correct
      identification of letters in the periphery, supporting the notion of a different
      distribution of lateral masking. A numerical characterization of individual FRFs-
      C2R--reliably distinguishes between dyslexics and ordinary readers. The wider
      distribution of recognition, similar across the various subtypes of dyslexia,
      suggests a general characteristic of visual perception, and possibly a different
      visual-attentional mode.

PMID- 15246757
TI  - Chromatic induction in humans: how are the cone signals combined to provide
      opponent processing?
AB  - We investigated the effect of 16 isoluminant chromatic surrounds on the perceived
      colour of an enclosed grey test-field at photopic (43 cd/m2) conditions. Stimuli
      were shown on a grey background identical to the test-field. Use of these stimuli
      implies that activations of receptoral (cS, cM, and cL) and postreceptoral (cM
      cL, cS-(cM+cL)) mechanisms by surround colours are known quantitatively. This
      allows to predict shifts in colour of the test-field in terms of receptoral
      (adaptation) as well as postreceptoral (contrast) mechanisms assuming a standard
      two-stage model. Predictions are tested using matching and hue compensation
      procedures. Both procedures yield comparable results that are consistent with the
      assumption that postreceptoral mechanisms explain the observed shifts in
      perceived colour.

PMID- 15246758
TI  - Using the deadly mu-conotoxins as probes of voltage-gated sodium channels.
AB  - Mu-Conotoxins (mu-CTX) are potent Na channel inhibitory peptides isolated from
      the venom of the predatory marine snail Conus geographus. Mu-CTXs exert their
      biological action by physically occluding the ion-conducting pore of voltage
      gated Na (Na(v)) channels with a 1:1 stoichiometry in an all-or-none fashion.
      This article reviews our current knowledge of the mechanism of mu-CTX and the
      associated structural and functional insights into its molecular target--Na(v)
      channels.

PMID- 15246759
TI  - Differential dynamics of dinophysistoxins and pectenotoxins between blue mussel
      and common cockle: a phenomenon originating from the complex toxin profile of
      Dinophysis acuta.
AB  - Different toxin profiles of dinophysistoxins and pectenotoxins have been reported
      before between blue mussel and other bivalve species, such as common cockle,
      razor clam, clams, etc. Comparison of toxins present in plankton in mussel
      growing areas and in cockle growing areas, respectively, showed there was no
      particular incidence of dinophysistoxin-2 (DTX2) in plankton from mussel growing
      areas that could account for the higher percentage of DTX2 in relation to okadaic
      acid (OA) found in mussels; or of pectenotoxin-2 in cockle growing areas that
      could explain the higher levels of pectenotoxin-2 seco acid (PTX2sa) found in
      cockles. A detoxification experiment between mussels and cockles showed the
      higher percentage of DTX2 in mussels was due to slower elimination of this toxin
      in relation to OA; while the lower levels of PTX2sa were due to quicker
      elimination by mussels than by cockles. The slower elimination of DTX2 explains
      why in late summer and autumn this toxin gradually accumulate in mussels
      throughout the entire coast, while other bivalves species have a lower percentage
      of DTX2, very close to the 3:2 OA:DTX2 ratio found in natural plankton
      assemblages when Dinophysis acuta predominates. In the clam Donax spp., DTX2
      concentration also tends to build up in relation to OA, this being made up
      predominantly by free DTX2 while esterified DTX2 is found only in trace levels
      (similarly to what is found in mussel for DTX2). We hypothesise that the
      esterified forms of OA and DTX2 are more easily eliminated than the free forms,
      by all shellfish species. The free forms are more difficult to eliminate. This is
      particularly notable in these two species that present a very low conversion of
      DTX2 into acyl esters. The high pool of free toxins is partially responsible for
      these two species (mussel and Donax clams) being the sentinel species for DSP
      contamination throughout the Portuguese coast. Esters of OA and DTX2 were found
      in a plankton sample where D. acuta was the predominant toxic species found. The
      nature of the esters remains to be elucidated. The boiling of these DTX2 esters
      seems to favour the rearrangement of the parent molecule to the DTX2 isomer,
      DTX2i, recoverable after alkaline hydrolysis. The isomerization was also observed
      with DTX2 esters present in mussel, but thus not appear to occur with the same
      extent with free DTX2.

PMID- 15246760
TI  - A rapid and repeatable method for venom extraction from cubozoan nematocysts.
AB  - Various comparative studies into the biological activity and relative toxicity of
      cubozoan venoms have been investigated, in particular the venom from the
      potentially lethal cubozoan Chironex fleckeri. Efficient and reliable extraction
      of venom from nematocysts is essential before any research into venom toxicity
      can be conducted and previous cited methods of extraction have varied greatly,
      each with their own associated problems. A new standardised technique for the
      recovery of venom from nematocysts of cubozoans is investigated to decrease the
      variation displayed between authors due to differing extraction techniques. The
      use of a mini bead mill beater, as investigated in this trial, allows for the
      rapid extraction of venom from nematocysts and is devoid of the previously
      isolated problems experienced with other methods of venom isolation, such as
      excessive heat build up.

PMID- 15246762
TI  - Rapid and efficient identification of cysteine-rich peptides by random screening
      of a venom gland cDNA library from the hexathelid spider Macrothele gigas.
AB  - We identified novel 10 multi-cysteine peptides, namely Magi 7-16, from the spider
      Macrothele gigas by simple random cDNA screening of the venom gland. Mass
      analysis of the crude venom detected the mass numbers of the cross-linked forms
      of all peptides, confirming their presence in the venom. Magi 11, a C-terminus
      amidated peptide, was chemically synthesized and was indistinguishable from the
      native peptide proving the feasibility of the method for peptide identification.
      Moreover, toxicological assays showed diverse lethal or paralytic activities of
      these peptide toxins on mice and/or insects.

PMID- 15246761
TI  - Anti-sera raised in rabbits against crotoxin and phospholipase A2 from Crotalus
      durissus cascavella venom neutralize the neurotoxicity of the venom and crotoxin.
AB  - Crotoxin, the principal neurotoxin in venom of the South American rattlesnakes
      Crotalus durissus terrificus and Crotalus durissus cascavella, contains a basic
      phospholipase A2 (PLA2) and an acidic protein, crotapotin. In this work, we
      examined the ability of rabbit anti-sera against crotoxin and its PLA2 subunit to
      neutralize the neurotoxicity of venom and crotoxin from C. d. cascavella in mouse
      phrenic nerve-diaphragm and chick biventer cervicis preparations. Immunoblotting
      showed that the anti-sera recognized C. d. cascavella crotoxin and PLA2. This was
      confirmed by ELISA, with both anti-sera having end-point dilutions of 3 x 10(-6).
      Anti-crotoxin serum neutralized the neuromuscular blockade in phrenic nerve
      diaphragm muscle preparations at venom or crotoxin:anti-serum ratios of 1:2 and
      1:3, respectively. Anti-PLA2 serum also neutralized this neuromuscular activity
      at a venom or crotoxin:anti-serum ratio of 1:1. In biventer cervicis
      preparations, the corresponding ratio for anti-crotoxin serum was 1:3 for venom
      and crotoxin, and 1:1 and 1:2 for anti-PLA2 serum. The neutralizing capacity of
      the sera in mouse preparations was comparable to that of commercial anti-serum
      raised against C. d. terrificus venom. These results show that anti-sera against
      crotoxin and PLA2 from C. d. cascavella venom neutralized the neuromuscular
      blockade induced by venom and crotoxin in both nerve-muscle preparations, with
      the anti-serum against crotoxin being slightly less potent than that against
      crotoxin.

PMID- 15246763
TI  - Effect of a recombinant Lys49PLA2 myotoxin and Lys49PLA2-derived synthetic
      peptides from Agkistrodon species on membrane permeability to water.
AB  - The aim of this work was to study the effect of recombinant ACL myotoxin, a
      Lys49PLA2 from Agkistrodon contortrix laticinctus snake venom and Lys49PLA2
      derived synthetic peptides corresponding to the region 115-129 of venom of the
      two different Agkistrodon species on water permeability in the toad urinary
      bladder. The water flow through the membrane was measured gravimetrically in bag
      preparations of the bladder. The addition of recombinant ACL myotoxin-MBP
      (maltose binding protein) fusion protein (10 nM) to the bathing solution
      significantly increased (above 60%) the water transport compared with the control
      hemibladders. The addition of the Lys49PLA2-derived synthetic peptides in several
      concentrations to the bathing solution did not affect the water transport across
      membrane. These results suggest that the ACL myotoxin effect on water transport
      is not related to the cytotoxic C-terminal region.

PMID- 15246764
TI  - Rattlesnake venom induces apoptosis by stimulating PC-PLC and upregulating the
      expression of integrin beta4, P53 in vascular endothelial cells.
AB  - In the previous studies, we found that phosphatidylcholine-specific phospholipase
      C (PC-PLC) was implicated in apoptosis induced by rattlesnake venom in vascular
      endothelial cells (VEC) [Biochem. Biophys. Res. Commun. (1997b) 223, 182]. In
      order to find out other signal elements in this pathway and the mechanisms by
      which PC-PLC mediates apoptosis induced by rattlesnake venom in VEC, the
      expression of integrin beta4 and P53 was evaluated when the activity of PC-PLC
      was suppressed by D609 (tricyclodecan-9-yl-xanthogenate), a specific inhibitor of
      this enzyme. The increase of integrin beta4 and P53 expression induced by the
      venom was markedly suppressed when apoptosis of VEC was inhibited by D609. The
      data indicated that integrin beta4 and P53 play important roles in signal
      transduction of apoptosis induced by rattlesnake venom, and that PC-PLC might
      regulate apoptosis by up-regulating the expression of integrin beta4 and P53 in
      VEC.

PMID- 15246765
TI  - Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5,
      a lethal Phoneutria nigriventer spider toxin.
AB  - The primary goal of this study was to determine whether Tx2-5, a sodium channel
      selective toxin obtained from the venom of the spider Phoneutria nigriventer,
      produced penile erection by means of nitric oxide mechanism. Toxin identity was
      analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating
      mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro
      L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS
      inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse)
      injection challenged the hypothesis above. Controls were injected with the D
      isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile
      erections in about half the animals treated, while 7-NI completely abolished this
      effect. Interestingly 7-NI also abolished all the other symptoms of intoxication
      induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5
      killed all the animals of the control group and no one in the 7-NI-treated group.
      We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome
      that include penile erection, hypersalivation and death by respiratory distress
      or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME
      reduces the penile erection and partially protects from the lethal effects of Tx2
      5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes
      all the toxic effects of Tx2-5, including penile erection and death suggesting
      that nNOS is the major player in this intoxication; (4) toxins from other animals
      that affect sodium channels in the same way as Tx2-5 and induce similar toxic
      syndromes may have as a major common target, the activation of nitric oxide
      synthases.

PMID- 15246766
TI  - Acute toxicity of gymnodimine to mice.
AB  - The acute toxicity of the phycotoxin gymnodimine to female Swiss mice by
      intraperitoneal injection and by oral administration has been determined.
      Gymnodimine was highly toxic by injection, the LD50 being only 96 microg/kg.
      Animals either died within 10 min of injection or made a full recovery with no
      perceptible long-term effects. Gymnodimine was also toxic after oral
      administration by gavage (LD50 755 microg/kg), but was much less toxic when
      administered with food. No signs of toxicity were seen in mice voluntarily
      ingesting food containing gymnodimine at a level sufficient to give a dose of
      approximately 7500 microg/kg. Pre-treatment with physostigmine or neostigmine
      protected against injected gymnodimine, suggesting that the latter exerts its
      toxic effects via blockade of nicotinic receptors at the neuromuscular junction.
      The low toxicity of gymnodimine when ingested with food suggests that this
      compound is of low risk to humans, a conclusion that is consonant with anecdotal
      evidence for the absence of harmful effects in individuals consuming shellfish
      contaminated with gymnodimine.

PMID- 15246767
TI  - Dantrolene protects hippocampal cells from damage induced by TsTX, an alpha
      scorpion toxin from Tityus serrulatus.
AB  - We examined the effects of dantrolene, an inhibitor of intracellular calcium
      release, on alterations associated with the intrahippocampal injection of the
      TsTX scorpion toxin. Male Wistar rats (230-250 g) were injected with Ringer
      solution (1 microl; n = 6); TsTX toxin (1 microg/microl; n = 8); and dantrolene
      (10.0 mg/kg) plus TsTX toxin (1 microg/microl; n = 6). After injection,
      electroencephalographic (EEG) recordings and observation of animals behaviour
      were performed continuously for 4 h. One week later, animals were submitted to
      histopathological analysis. TsTX caused electrographic seizure expressed by
      moderate or intense discharges and neuronal loss in hippocampal areas in all
      injected animals (n = 8). Dantrolene reduced the effect of TsTX. Thus, 67% of
      rats (four out of six) treated with toxin and dantrolene had electrographic
      convulsions, but only for 30 min after injection and none of them presented
      neuronal damage. Dantrolene or Ringer had no effects on the EEG.

PMID- 15246768
TI  - Determination of tetramine in marine gastropods by liquid
      chromatography/electrospray ionization-mass spectrometry.
AB  - Tetramine (tetramethylammonium ion) is found at high levels (several mg/g) in the
      salivary gland of buccinid gastropods and has been involved in numerous poisoning
      incidents after ingestion of those gastropods. A sensitive and selective
      determination method for tetramine, which is based on a combination of liquid
      chromatography (LC) and electrospray ionization-single quadrupole mass
      spectrometry (ESI-MS), was developed. Following separation by LC on a cation
      exchange column, tetramine was easily detected by simultaneous monitoring of a
      molecular ion (m/z 74) at a cone voltage of 30 V and a fragment ion (m/z 58) at
      70 V. A linear calibration curve was obtained in the range of 0.1-100 ng by
      plotting the peak areas of the molecular ion versus the amounts of tetramine.
      Spiking experiments demonstrated that tetramine in gastropod tissues can be
      determined by the LC/ESI-MS method, without being affected by sample matrices as
      well as the extration procedure. Applications of the new method to gastropod
      samples revealed that a small amount of tetramine is contained even in mid-gut
      gland and muscle and that tetramine in the salivary gland diffuses to other
      tissues during boiling and slow thawing.

PMID- 15246769
TI  - The in vitro neuromuscular activity of Indo-Pacific sea-snake venoms: efficacy of
      two commercially available antivenoms.
AB  - We examined the neurotoxicity of the following sea snake venoms: Enhydrina
      schistosa (geographical variants from Weipa and Malaysia), Lapemis curtus (Weipa
      and Malaysia), Laticauda colubrina, Aipysurus laevis, Aipysurus fuscus and
      Aipysurus foliosquamatus. Venom from a terrestrial snake, Notechis scutatus
      (tiger snake), was used as a reference. All venoms (1 and 3 microg/ml) abolished
      indirect twitches of the chick biventer cervicis muscle and significantly
      inhibited responses to ACh (1 mM) and CCh (20 microM), but not KCl (40 mM),
      indicating the presence of post-synaptic toxins. Prior administration (10 min) of
      CSL sea snake antivenom (1 unit/ml) attenuated the twitch blockade produced by N.
      scutatus venom and all sea snake venoms (1 microg/ml). Prior administration (10
      min) of CSL tiger snake antivenom (1 unit/ml) attenuated the twitch blockade of
      all venoms except those produced by E. schistosa (Malaysia and Weipa) and A.
      foliosquamatus. Administration of CSL sea snake antivenom (1 unit/ml) at t90
      (i.e. time at which 90% inhibition of initial twitch height occurred) reversed
      the inhibition of twitches (20-50%) produced by the sea snake venoms (1
      microg/ml) but not by N. scutatus venom (1 microg/ml). CSL tiger snake antivenom
      (1 unit/ml) administered at t90 produced only minor reversal (i.e. 15-25%) of the
      twitch blockade caused by L. curtus (Weipa), A. foliosquamatus, L. colubrina and
      A. laevis venoms (1 microg/ml). Differences in the rate of reversal of the
      neurotoxicity produced by the two geographical variants of E. schistosa venom,
      after addition of CSL sea snake antivenom, indicate possible differences in venom
      components. This study shows that sea snake venoms contain potent post-synaptic
      activity that, despite the significant genetic distances between the lineages,
      can be neutralised with CSL sea snake antivenom. However, the effects of CSL
      tiger snake antivenom are more variable.

PMID- 15246770
TI  - Protective effects of aprotinin on respiratory and cardiac abnormalities induced
      by Mesobuthus tamulus venom in adult rats.
AB  - Role of aprotinin (kallikrein-kinin synthesis inhibitor) in preventing the cardio
      respiratory toxicity induced by Mesobuthus tamulus (BT) venom was evaluated. The
      effects of BT venom (5 mg/kg) on mean arterial pressure (MAP), heart rate (HR),
      respiratory rate (RR), lung compliance and pulmonary water content were examined.
      BT venom produced alterations in MAP, HR and RR. The MAP changes were seen as an
      immediate fall (within 2 s) followed by a rise and subsequent progressive fall.
      The HR was decreased drastically after venom and never returned to initial value.
      The respiratory changes were manifested as prolonged apnea with intermittent
      shallow breathing. The animals died within 30-60 min. In these animals, the lung
      compliance was decreased as compared to saline treated controls and there was
      significant increase in pulmonary water content. In aprotinin pre-treated group,
      there was decrease in MAP, HR and RR within 2 s which returned to pre-venom level
      within 15 min and remained at that level thereafter. The animals survived for the
      period of observation (i.e. up to 120 min). The compliance and pulmonary water
      content in these animals were similar to control animals. The results indicate
      that aprotinin protects against the BT venom-induced cardio-pulmonary toxicity.

PMID- 15246771
TI  - AlphaA-Conotoxin OIVA defines a new alphaA-conotoxin subfamily of nicotinic
      acetylcholine receptor inhibitors.
AB  - The venoms of cone snails are rich in multiply disulfide-crosslinked peptides,
      the conotoxins. Conotoxins are grouped into families on the basis of shared
      cysteine patterns and homologous molecular targets. For example, both the kappaA-
      and alphaA-conotoxin families share the same Class IV Cys pattern (-CC-C-C-C-C-),
      but differ in their molecular targets. The kappaA-conotoxins are excitatory
      toxins that purportedly block potassium channels, while the alphaA-conotoxins are
      paralytic conotoxins that inhibit nicotinic acetylcholine receptors (nAChRs). In
      this work, we describe the isolation and characterization of a novel Conus
      peptide from venom milked from Hawaiian specimens of Conus obscurus. This peptide
      shares the Class IV Cys pattern but differs from both previously characterized
      alphaA- and kappaA-conotoxins in the spacing of amino acids between Cys resides.
      However, the peptide is similar to previously characterized alphaA-conotoxins in
      its paralytic effects on fish and its antagonist activity on the neuromuscular
      nAChR. Unexpectedly, the peptide differs in its disulfide bonding from alphaA
      conotoxin PIVA. We have named this unique peptide alphaA-conotoxin OIVA, and we
      consider it the defining member of a subfamily of alphaA-conotoxins that we
      designate the alphaA(1-3)-conotoxins to identify them by their unique disulfide
      bonding framework. These results indicate that the alphaA-conotoxin family is
      both more structurally diverse and broadly distributed than previously believed.

PMID- 15246772
TI  - A new hemorrhagic metalloprotease from Bothrops jararacussu snake venom:
      isolation and biochemical characterization.
AB  - A hemorrhagic metalloprotease, named BjussuMP-I, was isolated from Bothrops
      jararacussu snake venom by a combination of gel filtration on Sephacryl S-200
      (0.01 M Tris-HCl, pH 7.6 buffer) and Phenyl Sepharose CL-4B chromatography (0.01
      M Tris-HCl plus 4 M NaCl, pH 8.6 buffer, followed by a concentration gradient
      from 4 to 0 M NaCl at 25 degrees C in the same buffer). BjussuMP-I is a 60 kDa
      protein with a pI approximately 5.5, which induced hemorrhage after intradermal
      injection in mice, with a minimum hemorrhagic dose of 4.0 microg. The hemorrhagic
      activity of BjussuMP-I was totally abolished after incubation with a chelating
      agent (EDTA), corroborating the metal-dependency of this effect. BjussuMP-I shows
      proteolytic activity on casein and fibrinogen, although having an activity lower
      than that of crude B. jararacussu venom and the metalloprotease neuwiedase
      isolated from Bothrops neuwiedi snake venom. It was recognized by anti-neuwiedase
      antibodies, with a reaction of partial immunologic identity. BjussuMP-I also
      shows bactericidal activity against Escherichia coli and Staphylococcus aureus.
      This is the first report on the isolation and characterization of a high
      molecular weight hemorrhagic metalloprotease (BjussuMP-I) from B. jararacussu
      venom, which may play a relevant role in local and systemic bleeding which
      characterizes Bothrops envenomations.

PMID- 15246773
TI  - 5Alpha-reductase inhibition activity of steroids isolated from marine soft
      corals.
AB  - The aim of this study is to determine the 5alpha-reductase inhibitory activity of
      several new steroidal compounds PR-01-PR-07 by measuring the conversion of [3H]T
      to[3H]DHT in Penicillium crustosum broths. These compounds were obtained from
      marine soft corals collected on the coasts of Andaman and Nicobar at Hori, Natkal
      and Kalipur (Diglipur) Islands and identified as Sinularia grandilobata
      Verseveldt, Sinularia crassa Tixier- Durivault, Sinularia gravis Tixier-
      Durivault, Sinularia sp., Lobophytum sp., Lobophytum crassum and Cladiella sp. PR
      01-PR-04 significantly inhibited the conversion of [3H]T to [3H]DHT (P < 0.05)
      whereas PR-05 and PR-06 did not show an appreciable difference (P > 0.05) in this
      model. On the other hand PR-07 stimulated (P < 0.05) the enzymatic reaction.

PMID- 15246774
TI  - Synthesis of polyhydroxysterols (IV): synthesis of 24-methylene-cholesta
      3beta,5alpha,6beta,19-tetrol, a cytotoxic natural hydroxylated sterol.
AB  - The cytotoxic, polyhydroxylated sterol 24-methylene-cholesta
      3beta,5alpha,6beta,19-tetrol (1), previously isolated from the soft corals
      Nephthea albida and N. tiexieral verseveldt, was synthesized using stigmasterol
      as the starting material by 10 steps in 9% overall yield. The spectral data and
      physical constants of 1 were identical with those of the natural product. This is
      the first report of the synthesis of 1.

PMID- 15246775
TI  - Neighboring group participation. Part 15. Stereoselective synthesis of some
      steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5alpha
      reductase.
AB  - During the alkaline methanolysis of 3beta-acetoxy-21-chloromethyl-pregn-5-ene
      20beta-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization
      occurs, in the course of which 17beta-[3-(N-phenyl)tetrahydrooxazin-2-on-6
      yl]androst-5-en-3beta-ol and its p-substituted phenyl derivatives are formed. The
      cyclization takes place with (N(-)-6) neighboring group participation. Oppenauer
      oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the
      corresponding delta4-3-ketosteroids. The structures of the new compounds were
      proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques
      such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI50) of the delta4-3
      ketosteroids on 5alpha-reductase were studied.

PMID- 15246776
TI  - Development of a highly sensitive and specific new testosterone time-resolved
      fluoroimmunoassay in human serum.
AB  - A new time-resolved fluoroimmunoassay (TR-FIA) of testosterone in serum is
      described, using a biotinylated testosterone tracer, with a long spacer arm
      between biotin and testosterone, coupled to the C3 of the testosterone: a
      biotinylaminodecane carboxymethyloxime testosterone. This tracer affords a great
      sensitivity of the standard curve, because a amount of 0.3 pg of testosterone can
      be significantly measured on the testosterone standard curve. The "functional"
      sensitivity is at least equal to 21 pg/ml of serum. The specificity of the assay
      is insured by a celite chromatographic step on new minicolumns before
      immunoassay. The variation coefficient of inter-series reproducibility measured
      on low and normal testosterone levels in untreated and testosterone treated
      hypogonadal men were between 2.17 and 5.07%. The accuracy test, (overload and
      dilution tests) gave satisfying results. Moreover, in a comparison with GCMS, it
      appeared that the correlation coefficient was 0.992 and no significant difference
      could be exhibited between the two methods. Consequently, this specific,
      sensitive reproducible and easy to use method is well suited to the measurement
      of testosterone in clinical and pharmacological conditions.

PMID- 15246777
TI  - 15Alpha-hydroxyprogesterone in male sea lampreys, Petromyzon marinus L.
AB  - There is growing evidence that sea lampreys, Petromyzon marinus L., produce
      gonadal steroids differing from those of other vertebrates by possessing an
      additional hydroxyl group at the C15 position. Here we demonstrate that sea
      lamprey testes produce 15alpha-hydroxyprogesterone (15alpha-P) in vitro when
      incubated with tritiated progesterone, that 15alpha-P is present in the plasma of
      sea lampreys, and that plasma concentrations of immunoreactive (ir) 15alpha-P
      rise dramatically in response to injections of gonadotropin-releasing hormone
      (GnRH). The identity of the tritiated 15alpha-P produced in vitro was confirmed
      by co-elution with standard 15alpha-P on high performance liquid chromatography,
      co-elution with standard and acetylated 15alpha-P on thin layer chromatography,
      and specific binding to antibodies raised against standard 15alpha-P. The in
      vitro conversion was used to produce tritiated 15alpha-P label for a
      radioimmunoassay (RIA), which is able to detect 15alpha-P in amounts as low as 2
      pg per tube. The RIA has been used to measure the plasma concentrations of
      15alpha-P in males given two serial injections, 24 h apart, of either lamprey
      GnRH I or GnRH III (50, 100, or 200 microg/kg) or saline control, with plasma
      being sampled 8 and 24 h after the second injection. Plasma concentrations of ir
      15alpha-P rose from < 1 to 36 ng/ml (mean of all treatments) 8 h after injection
      and declined within 24 h. This is the first time that an RIA has detected such
      high steroid concentrations in lampreys. This finding is suggestive of a role for
      15alpha-P in control of reproduction in the sea lamprey.

PMID- 15246778
TI  - Stereoselective synthesis of (22R)- and (22S)-castasterone/ponasterone A hybrid
      compounds and evaluation of their molting hormone activity.
AB  - Two stereoisomers of a castasterone/ponasterone A hybrid compound, the (20R,22R)
      and (20R,22S)-isomers of 2alpha,3alpha,20,22-tetrahydroxy-5alpha-cholestan-6-one,
      were synthesized stereoselectively and their binding activity to the ecdysteroid
      receptor was determined. From the concentration-response curve for the inhibition
      of the incorporation of tritiated ponasterone A into ecdysteroid receptor
      containing insect cells, the concentration (IC50) required to inhibit 50% of the
      incorporation of radioactivity into cells was evaluated. The IC50 values of the
      (22R)- and (22S)-isomers were determined to be 0.30 and 38.9 microM against Kc
      cells, respectively, indicating that the (22R)-isomer is about 100 times more
      potent than the corresponding (22S)-isomer. IC50 values of these compounds
      against lepidopteran Sf-9 cells were determined to be 0.36 and 12.9 microM,
      respectively. The molting hormonal effect was examined in a Chilo suppressalis
      integument system and the 50% effective concentration for the stimulation of N
      acetylglucosamine incorporation into the cultured integument was determined to be
      2.7 microM for the (22R)-isomer, while the (22S)-isomer was inactive. On the
      other hand, both isomers did not show brassinolide-like activity in the rice
      lamina inclination assay.

PMID- 15246779
TI  - The synthesis of functionalized 13,14-seco-steroids via Grob fragmentation.
AB  - A synthetic methodology for the synthesis of 13,14-seco-steroids with
      substituents at C-14 and C-17 is described. The approach involves Grob
      fragmentation of 14beta-hydroxy-17beta-tosylates, hydroboration-oxidation of the
      intermediate delta13(17)-olefin, and hydride reduction of the 14-ketone. An
      unambiguous structural assignment of (13R,14S,17S)-14,17-diacetoxy-3-methoxy
      7alpha-methyl-13,14-secoestra-1,3,5(10)-triene was determined by X-ray analysis.

PMID- 15246780
TI  - Synthesis of 13,14-secotestosterone derivatives.
AB  - A number of testosterone analogs with a 13,14-secosteroidal fragment have been
      prepared from (13S)-13-iodo-6beta-methoxy-3alpha, 5-cyclo-13,14-seco-5alpha
      androstan-14,17-dione. The key steps involved stereoselective deiodination of the
      starting compound with triphenylphosphine and selective protection of the 17-keto
      group with trimethylsilylcyanide. Removal of iodine at C-13 proceeded with
      inversion of the configuration at C-13, which has been established by X-ray
      crystallography. 13,14-Secotestosterone analogues substituted and non-substituted
      at C-14 have been prepared. The obtained compounds containing flexible CD ring
      fragments are of great interest for comparative studies in biological tests
      together with testosterone and other steroids with a rigid tetracyclic skeleton.

PMID- 15246781
TI  - Reaction of (13S)-13-iodo-6beta-methoxy-3alpha,5-cyclo-13,14-seco-5alpha
      androstane-14,17-dione with hydroxylamine and its application to the synthesis of
      new 13,14-seco steroids.
AB  - The synthesis of 13,14-seco steroids starting from easily available (13S)-13-iodo
      6beta-methoxy-3alpha,5-cyclo-13,14-seco-5alpha-androsta-14,17-dione is described.
      The C-17 ketone was converted regioselectively into its oxime with simultaneous
      stereoselective deiodination at C-13. The remaining C-14 carbonyl group was then
      reduced stereoselectively with Ca(BH4)2. The configurations at the relevant
      stereocenters of the thus obtained hydroxy oxime were determined by X-ray
      analysis. Successful regeneration of the C-17 carbonyl group was achieved by
      treatment of the corresponding oxime acetate with TiCl3.

PMID- 15246782
TI  - Inaccurate mimicry and predator ecology.

PMID- 15246783
TI  - A mathematical model of tumour angiogenesis, regulated by vascular endothelial
      growth factor and the angiopoietins.
AB  - Angiogenesis--the growth of new blood vessels from existing ones--is a
      prerequisite for the growth of solid tumours beyond a diameter of approximately 2
      mm. In recent years, the angiopoietins have emerged as important regulators of
      angiogenesis. They mediate a delicate balance between vascular quiescence,
      regression and new growth, but their mechanism of action is not fully understood.
      This work attempts to provide a mathematical description of the role of the
      angiopoietins in angiogenesis. The model is formulated within the framework of
      reinforced random walks, which allows easy transition between the continuum
      (macroscopic) and discrete (microscopic) forms. Model predictions are in
      qualitative agreement with experimental observations, and may have implications
      for anti-cancer therapies based on the prevention of angiogenesis.

PMID- 15246785
TI  - A theory of drug tolerance and dependence I: a conceptual analysis.
AB  - A mathematical model of drug tolerance and its underlying theory is presented.
      The model extends a first approach, published previously. The model is
      essentially more complex than the generally used model of homeostasis, which is
      demonstrated to fail in describing tolerance development to repeated drug
      administrations. The model assumes the development of tolerance to a repeatedly
      administered drug to be the result of a regulated adaptive process. The oral
      detection and analysis of exogenous substances is proposed to be the primary
      stimulus for the mechanism of drug tolerance. Anticipation and environmental cues
      are in the model considered secondary stimuli, becoming primary only in
      dependence and addiction or when the drug administration bypasses the natural
      oral-route, as is the case when drugs are administered intravenously. The model
      considers adaptation to the effect of a drug and adaptation to the interval
      between drug taking autonomous tolerance processes. Simulations with the
      mathematical model demonstrate the model's behavior to be consistent with
      important characteristics of the development of tolerance to repeatedly
      administered drugs: the gradual decrease in drug effect when tolerance develops,
      the high sensitivity to small changes in drug dose, the rebound phenomenon and
      the large reactions following withdrawal in dependence. The mathematical model
      verifies the proposed theory and provides a basis for the implementation of
      mathematical models of specific physiological processes. In addition, it
      establishes a relation between the drug dose at any moment, and the resulting
      drug effect and relates the magnitude of the reactions following withdrawal to
      the rate of tolerance and other parameters involved in the tolerance process. The
      present paper analyses the concept behind the model. The next paper discusses the
      mathematical model.

PMID- 15246784
TI  - A general mathematical framework to model generation structure in a population of
      asynchronously dividing cells.
AB  - In otherwise homogeneous cell populations, individual cells undergo asynchronous
      cell cycles. In recent years, interest in this fundamental observation has been
      boosted by the wide usage of CFSE, a fluorescent dye that allows the precise
      estimation by flow cytometry of the number of divisions performed by different
      cells in a population, and thus the generation structure. In this work, we
      propose two general mathematical frameworks to model the time evolution of
      generation structure in a cell population. The first modeling framework is more
      descriptive and assumes that cell division time is distributed in the cell
      population, due to intrinsic noise in the molecular machinery in individual
      cells; while the second framework assumes that asynchrony in cell division stems
      from randomness in the interactions individual cells make with environmental
      agents. We reduce these formalisms to recover two preexistent models, which build
      on each of the hypotheses. When confronted to kinetics data on CFSE labeled cells
      taken from literature, these models can fit precursor frequency distributions at
      each measured time point. However, they fail to fit the whole kinetics of
      precursor frequency distributions. In contrast, two extensions of those models,
      derived also from our general formalisms, fit equally well both the whole
      kinetics and individual profiles at each time point, providing a biologically
      reasonable estimation of parameters. We prove that the distribution of cell
      division times is not Gaussian, as previously proposed, but is better described
      by an asymmetric distribution such as the Gamma distribution. We show also that
      the observed cell asynchrony could be explained by the existence of a single
      transitional event during cell division. Based on these results, we suggest new
      ways of combining theoretical and experimental work to assess how much of noise
      in internal machinery of the cell and interactions with the environmental agents
      contribute to the asynchrony in cell division.

PMID- 15246786
TI  - A theory of drug tolerance and dependence II: the mathematical model.
AB  - The preceding paper presented a model of drug tolerance and dependence. The model
      assumes the development of tolerance to a repeatedly administered drug to be the
      result of a regulated adaptive process. The oral detection and analysis of
      exogenous substances is proposed to be the primary stimulus for the mechanism of
      drug tolerance. Anticipation and environmental cues are in the model considered
      secondary stimuli, becoming primary in dependence and addiction or when the drug
      administration bypasses the natural-oral-route, as is the case when drugs are
      administered intravenously. The model considers adaptation to the effect of a
      drug and adaptation to the interval between drug taking autonomous tolerance
      processes. Simulations with the mathematical model demonstrate the model's
      behaviour to be consistent with important characteristics of the development of
      tolerance to repeatedly administered drugs: the gradual decrease in drug effect
      when tolerance develops, the high sensitivity to small changes in drug dose, the
      rebound phenomenon and the large reactions following withdrawal in dependence.
      The present paper discusses the mathematical model in terms of its design. The
      model is a nonlinear, learning feedback system, fully satisfying control
      theoretical principles. It accepts any form of the stimulus-the drug intake-and
      describes how the physiological processes involved affect the distribution of the
      drug through the body and the stability of the regulation loop. The mathematical
      model verifies the proposed theory and provides a basis for the implementation of
      mathematical models of specific physiological processes.

PMID- 15246787
TI  - Multivariate analysis of noise in genetic regulatory networks.
AB  - Stochasticity is an intrinsic property of genetic regulatory networks due to the
      low copy numbers of the major molecular species, such as, DNA, mRNA, and
      regulatory proteins. Therefore, investigation of the mechanisms that reduce the
      stochastic noise is essential in understanding the reproducible behaviors of real
      organisms and is also a key to design synthetic genetic regulatory networks that
      can reliably work. We use an analytical and systematic method, the linear noise
      approximation of the chemical master equation along with the decoupling of a
      stoichiometric matrix. In the analysis of fluctuations of multiple molecular
      species, the covariance is an important measure of noise. However, usually the
      representation of a covariance matrix in the natural coordinate system, i.e. the
      copy numbers of the molecular species, is intractably complicated because
      reactions change copy numbers of more than one molecular species simultaneously.
      Decoupling of a stoichiometric matrix, which is a transformation of variables,
      significantly simplifies the representation of a covariance matrix and elucidates
      the mechanisms behind the observed fluctuations in the copy numbers. We apply our
      method to three types of fundamental genetic regulatory networks, that is, a
      single-gene autoregulatory network, a two-gene autoregulatory network, and a
      mutually repressive network. We have found that there are multiple noise
      components differently originating. Each noise component produces fluctuation in
      the characteristic direction. The resulting fluctuations in the copy numbers of
      the molecular species are the sum of these fluctuations. In the examples, the
      limitation of the negative feedback in noise reduction and the trade-off of
      fluctuations in multiple molecular species are clearly explained. The analytical
      representations show the full parameter dependence. Additionally, the validity of
      our method is tested by stochastic simulations.

PMID- 15246788
TI  - A computational algebra approach to the reverse engineering of gene regulatory
      networks.
AB  - This paper proposes a new method to reverse engineer gene regulatory networks
      from experimental data. The modeling framework used is time-discrete
      deterministic dynamical systems, with a finite set of states for each of the
      variables. The simplest examples of such models are Boolean networks, in which
      variables have only two possible states. The use of a larger number of possible
      states allows a finer discretization of experimental data and more than one
      possible mode of action for the variables, depending on threshold values.
      Furthermore, with a suitable choice of state set, one can employ powerful tools
      from computational algebra, that underlie the reverse-engineering algorithm,
      avoiding costly enumeration strategies. To perform well, the algorithm requires
      wildtype together with perturbation time courses. This makes it suitable for
      small to meso-scale networks rather than networks on a genome-wide scale. An
      analysis of the complexity of the algorithm is performed. The algorithm is
      validated on a recently published Boolean network model of segment polarity
      development in Drosophila melanogaster.

PMID- 15246789
TI  - The impact of nonlinear functional responses on the long-term evolution of food
      web structure.
AB  - We investigate the long-term web structure emerging in evolutionary food web
      models when different types of functional responses are used. We find that large
      and complex webs with several trophic layers arise only if the population
      dynamics is such that it allows predators to focus on their best prey species.
      This can be achieved using modified Lotka-Volterra or Holling/Beddington
      functional responses with effective couplings that depend on the predator's
      efficiency at exploiting the prey, or a ratio-dependent functional response with
      adaptive foraging. In contrast, if standard Lotka-Volterra or Holling/Beddington
      functional responses are used, long-term evolution generates webs with almost all
      species being basal, and with additionally many links between these species.
      Interestingly, in all cases studied, a large proportion of weak links result
      naturally from the evolution of the food webs.

PMID- 15246790
TI  - Evolution of coordinated alternating reciprocity in repeated dyadic games.
AB  - A genetic algorithm incorporating mutation and crossing-over was used to
      investigate the evolution of social behaviour in repeated Prisoner's Dilemma,
      Chicken (Hawk-Dove), Battle of the Sexes, and Leader games. The results show that
      the strategic structure of an interaction has a crucial determining effect on the
      type of social behaviour that evolves. In particular, simulations using repeated
      Prisoner's Dilemma and Chicken (Hawk-Dove) games lead to the emergence of genes
      coding for symmetric reciprocity and the evolution of mutual cooperation, whereas
      simulations using repeated Battle of the Sexes and Leader games lead to near
      fixation of genes coding for asymmetric strategic choices and the evolution of
      coordinated alternating reciprocity. A mechanism is suggested whereby, in games
      with asymmetric equilibrium points, coordinated alternating reciprocity might
      evolve without insight or communication between players.

PMID- 15246791
TI  - Population models of sperm-dependent parthenogenesis.
AB  - Organisms that reproduce by sperm-dependent parthenogenesis are asexual clones
      that require sperm of a sexual host to initiate egg production, without the
      genome of the sperm contributing genetic information to the zygote. Although
      sperm-dependent parthenogenesis has some of the disadvantages of sex (requiring a
      mate) without the counterbalancing advantages (mixing of parental genotypes), it
      appears amongst a wide variety of species. We develop initial models for the
      density-dependent dynamics of animal populations with sperm-dependent
      parthenogenesis (pseudogamy or gynogenesis), based on the known biology of the
      common Enchytraeid worm Lumbricillus lineatus. Its sperm-dependent
      parthenogenetic populations are reproductive parasites of the hermaphrodite
      sexual form. Our logistic models reveal two alternative requirements for
      coexistence at density-dependent equilibria: (i) If the two forms differ in
      competitive ability, the form with the lower intrinsic birth rate must be
      compensated by a more than proportionately lower competitive impact from the
      other, relative to intraspecific competition, (ii) If the two forms differ in
      their intrinsic capacity to exploit resources, the sperm-dependent parthenogen
      must be superior in this respect and must have a lower intrinsic birth rate. In
      general for crowded environments we expect a sperm-dependent parthenogen to
      compete strongly for limiting resources with the sexual sibling species. Its
      competitive impact is likely to be weakened by its genetic uniformity, however,
      and this may suffice to cancel any advantage of higher intrinsic growth rate
      obtained from reproductive investment only in egg production. We discuss likely
      thresholds of coexistence for other sperm-dependent parthenogens. The fish
      Poeciliopsis monacha-lucida likewise obtains an intrinsic growth advantage from
      reduced investment in male gametes, and so its persistence is likely to depend on
      it being a poor competitor. The planarian Schmidtea polychroa obtains no such
      intrinsic benefit because it produces fertile sperm, and its persistence may
      depend on superior resource exploitation.

PMID- 15246793
TI  - Pre-hospital trauma care: a proposal for more efficient evaluation.
AB  - Although mortality is an important outcome parameter for pre-hospital trauma
      care, it is influenced by many factors other than pre-hospital trauma care alone.
      We therefore studied an alternative method to evaluate pre-hospital trauma care
      by calculating the change in probability of survival (Ps) according to the TRISS
      methodology, before and directly after the pre-hospital trauma care. Correlations
      between patient characteristics and a change in Ps were assessed. Further,
      required sample sizes were calculated for an 80% power to detect a hypothetical
      3% reduction in mortality and the corresponding change in Ps. In 140 of 191
      patients with an Injury Severity Score > or =16, the Ps did not change. In 36,
      the Ps increased and in 15 patients, the Ps decreased. Between these three
      groups, significant differences were found in Revised Trauma Score and age, but
      no clear differences in Injury Severity Score or mortality. A 3% difference in
      mortality would require 6800 patients, in contrast to 3500 when the change in Ps
      was the primary outcome parameter. A change in Ps is a promising outcome
      parameter for a more efficient evaluation of pre-hospital trauma care. A good
      collaboration is, however, required between ambulance services and the trauma
      center for reliable registration.

PMID- 15246794
TI  - Consensus on the pre-hospital approach to burns patient management.
AB  - Burns patients form a large group of trauma patients cared for by first-aiders,
      ambulance staff, nurses and doctors before reaching specialist care in hospital.
      Guidance for these important carers is often poor or confused and this engenders
      anxiety and detracts from optimal patient care. This paper outlines nine key
      steps in the initial management of burn patients in the pre-hospital environment
      based on current available evidence and a consensus of specialists all
      disciplines caring for burns patients. The basis of care should be that simple
      things should always be performed well.

PMID- 15246795
TI  - Rapid extrication from a car wreck.
AB  - Extrication of entrapped patients from car accidents takes time. To save time a
      new technique based on reversing the forces of the original crash by anchoring
      the rear of the vehicle and pulling the steering wheel and the front window
      pillars forward with chains is developed. In an experimental randomised trial of
      extrication of volunteers from car wrecks after frontal/oblique impacts we wanted
      to evaluate the time spent with a new extrication technique (n=6) compared to
      standard (n=6). Main outcome measures were time to patient free and to patient on
      a stretcher. It took significantly longer (s) with the standard than the new
      technique to start extrication [(60 (45, 70) versus 30 (30, 40), confidence
      interval (CI) 5-40, P=0.009], to patient free in the front seat [514+/-102 versus
      238+/-72, CI 163-389, P=0.001], backboard in place [543+/-102 versus 295+/-76, CI
      132-363, P=0.001], and patient on the stretcher ready for transport to the
      hospital [617+/-112 versus 387+/-65, CI 112-347, P=0.001]. Avoiding uncontrolled
      movements in the wreck was not more difficult with the new than the standard
      technique.

PMID- 15246796
TI  - Admission lactate level and the APACHE II score are the most useful predictors of
      prognosis following torso trauma.
AB  - BACKGROUND: Markers of dysoxic metabolism and scoring systems for triage have
      been widely used in critically injured patients. However, so far, no model is
      sufficiently reliable to predict the outcome in trauma victims. The purposes of
      the present study, therefore, were to determine whether a correlation exits
      between the main trauma scoring systems and the markers of dysoxic metabolism.
      Moreover, to assess if any of the admission parameters can be used to indicate
      outcome. METHODS: Sixty-four patients were included in this study. Admission
      data, including arterial lactate level, base deficit (BD), pH, revised trauma
      score (RTS), injury severity score (ISS), shock index (SI), and Acute Physiology
      and Chronic Health Evaluation (APACHE II), were collected and analysed by
      logistic regression analysis. Degree of association between continuous variables
      were calculated by either Pearson's or Spearman's correlation coefficient, where
      applicable. The dependence of lactate on two or more other variables was
      evaluated by multiple linear regression analysis. RESULTS: Logistic regression
      analysis showed that the fatal outcome following major torso trauma was
      principally associated with the APACHE II score and lactate. The specificity and
      the sensitivity of this logistic regression model was 94.6 and 79.2%,
      respectively. According to standardised linear regression coefficients, BD was
      the best single predictor of lactate, and APACHE II added a small amount of
      predictive power. The proportion of total variation in lactate level explained by
      base deficit, APACHE II and age is R2=85.2%. CONCLUSION: APACHE II score and the
      arterial lactate level are the most important determinants of clinical outcome in
      critically injured patients. A correlation exits between lactate and APACHE II
      and between lactate and base deficit.

PMID- 15246797
TI  - Assessment of the trauma evaluation and management (TEAM) module in Australia.
AB  - AIM: To assess the immediate effect on trauma-related knowledge of the trauma
      evaluation and management (TEAM) program applied to medical students in
      Australia. METHODS: 73 final year medical students from Melbourne were randomly
      assigned to two experimental groups (E1 and E2 who completed the TEAM program
      after a 20 item MCQ pre-test on trauma resuscitation and a second MCQ exam after
      the TEAM program) and two control groups (C1 and C2 who completed the pre- and
      post-MCQ exams before completing the TEAM module). All 73 students completed an
      evaluation questionnaire. Paired and unpaired t-tests were used for within and
      between groups comparisons. RESULTS: Groups C1 and C2 had similar mean scores in
      pre- and post-tests ranging from 57.2 to 60.5%. Groups E1 and E2 had similar pre
      test scores but increased their post-test scores (pre-test range 53.8-57.1% and
      post-test 68.8-77.4%, P < 0.05). On a scale of 1-5 with five being the highest, a
      score of four or greater was assigned by over 74% of the students that the
      objectives were met, over 80% that trauma knowledge was improved, 25-40% that
      clinical skills were improved with over 74% overall satisfaction. Over 75%
      assigned a score of four or greater suggesting the module be mandatory.
      CONCLUSIONS: After the TEAM program there was significant improvement in
      cognitive skills. The students strongly supported its introduction in the
      undergraduate curriculum.

PMID- 15246798
TI  - The increasing incidence of severe pelvic injury in motor vehicle collisions.
AB  - BACKGROUND: Pelvic fractures constitute a major cause of death and residual
      disability in motor vehicle collisions (MVC). To date there has been poor
      documentation of the epidemiology of severe pelvic injuries. A detailed
      retrospective examination of all abbreviated injury score (AIS) > or = 4 pelvic
      fractures sustained in occupants of MVCs seen at this lead trauma hospital over
      the last 12 years and in the province of Ontario over the last 6 years was
      completed. METHODS: The regional trauma centre registry and provincial database
      were used to obtain demographics, injuries, course in hospital and crash data on
      patients sustaining AIS > or = 4 pelvic injuries between May 1988 and April 2000.
      Data was analysed for drivers (D), front (FP) and rear (RP) passengers in 4-year
      blocks. Means (S.D.) with t-test for continuous and chi2 for categorical data
      were used for analysis. RESULTS: AIS > or = 4 pelvic fractures increased
      significantly in D and FP over 12 years and in RP over the last 8 years. Similar
      significant increases were seen throughout the province over the last 6 years. No
      significant change in age, sex, ISS or referral patterns was seen. Lateral impact
      collisions also increased over the study duration. Occupants with pelvic injury
      compared to all MVC survivors ISS > or = 16 during the same study period had a
      higher ISS (P < 0.001), utilised more blood in 24h and in total (P < 0.001) and
      died more frequently (P < 0.001). However, significantly fewer required ICU
      support (P < 0.01) which may reflect the associated injuries. Patients with
      pelvic fractures had significantly fewer head and chest injuries as well as fewer
      face and neck injuries. They did have significantly more injuries in the region
      of the pelvis including lumbar and sacral spine fractures, genitourinary, liver,
      spleen and lower extremity blood vessel, nerve and bone injuries. CONCLUSION:
      This study documented an increasing incidence of severe pelvic injury resulting
      from MVCs. This may be related to an associated increase in the incidence of
      lateral impact collisions. The role of side impact protection and side airbags,
      introduced to decrease injury severity in lateral impact collisions will require
      further study.

PMID- 15246799
TI  - Surgical treatment of displaced fractures of posterior column and posterior wall
      of the acetabulum.
AB  - We evaluated the results of open reduction and internal fixation of displaced
      posterior wall and posterior column fractures of the acetabulum. This was a
      prospective clinical evaluation of such cases where the main surgical strategy
      was open reduction and internal fixation with interfragmentary screws and
      reconstruction plates. Data on 11 patients treated by open reduction (all via
      Kocher-Langenbech approach)/internal fixation with interfragmentary screws and
      reconstruction plates were collected. The follow-up period was 61 (18-102)
      months. Reduction with a fracture gap of less than 2mm without articular stepping
      was achieved in all 11 cases. Postoperative complications developed in five
      patients, including subcutaneous haematoma in one, avascular necrosis of the
      femoral head (AVNFH) in one and heterotopic ossification (HO) in three. All but
      the patient with AVNFH, had anatomic radiological reduction, and good to
      excellent functional results. Open reduction and internal fixation with
      interfragmentary screws and reconstruction plates is the treatment of choice in
      displaced posterior wall and posterior column fractures of the acetabulum.

PMID- 15246800
TI  - Long-term outcomes of conservatively treated paediatric pelvic fractures.
AB  - The long-term orthopaedic, urologic, and psychiatric outcomes of patients treated
      non-operatively for unstable pelvic fractures were assessed. There were 55 males
      and 3 females with an average age of 7 (3-13). Eighty-one percent of the
      fractures were caused by motor vehicle accidents, and 68% by auto-pedestrian
      accidents. Thirty-four of the 58 fractures were type Tile type B and 24 were type
      C. Posterior urethral injury was determined in 41 patients, and head injury in
      21. Three patients with type C injury died within the first 3 days. After an
      average follow-up period of 7.4 years of the patients with type B injuries, leg
      length discrepancy of 1cm was determined in two, and limited motion associated
      with open-knee wound in one, and low back pain in two. Of the patients with type
      C injuries, low back pain was found in four, gait abnormality in three,
      sacroiliac ankylosis in one, and symphyseal ossification in two. Urethral
      stricture was determined in 11 patients, urinary incontinence in 6 and erectile
      dysfunction in 6. A total of 31 patients were diagnosed with 41 psychiatric
      illnesses, including dysthymic disorder, social phobia, post-traumatic stress
      disorder, and major depression. No difference was found in the treatment outcomes
      of the two groups. From a holistic standpoint, long hospital stays and urologic
      complications are associated with serious psychological problems, and thus should
      be considered during selection of treatment modality.

PMID- 15246801
TI  - Fractures of the posterior wall of the acetabulum: treatment using cannulated
      screws.
AB  - A total of 19 patients (16 males, 3 females) who had fractures of the posterior
      wall of the acetabulum were treated by open reduction and internal fixation.
      Their mean age was 40 years. There were five single-fragment fractures and 14
      comminuted. Fifteen patients were treated by fixation with cannulated screws only
      and four were treated with cannulated screws and reconstruction plates. Reduction
      and fixation of fragments was facilitated, and soft tissue dissection minimized,
      by the use of cannulated screws. Clinical results were excellent in nine hips,
      very good in one, good in six, and poor in three after follow-up of more than 2
      years. We think that preservation of the blood supply to the fracture fragments
      and careful placement of the fixation components is as important as rigid
      fixation of the fragments for the successful treatment of posterior-wall
      fractures of the acetabulum. The use of cannulated screws may be helpful for this
      purpose.

PMID- 15246802
TI  - Non-union of acetabular fractures.
AB  - Non-unions of acetabulum are rare. Seven cases of acetabular non-unions are
      reported in this retrospective study. Five out of our seven patients had either
      transverse or associated transverse with posterior wall fractures. All patients
      had surgical stabilisation of their index fractures. A diagnosis of non-union was
      made at an average of 5.8 months from the original injury based on clinical and
      radiological features. Five of the six patients who underwent re-stabilisation
      and bone grafting of the non-union healed where as the remaining one did not heal
      after two attempts at re-stabilisation and was treated with excision
      arthroplasty. Two of the healed five, subsequently developed osteoarthritis and
      had total hip arthroplasty where as one patient had already developed
      degeneration of his hip at the time of diagnosis and hence treated with total hip
      arthroplasty. Analysis of the non-unions confirmed that fixation was unstable in
      all with residual displacement seen in two of them. In conclusion acetabular
      fracture non-union appear to be associated with transverse fractures and unstable
      fixation.

PMID- 15246803
TI  - Outcome after surgery for Maisonneuve fracture of the fibula.
AB  - The aim of this study was to assess outcome in patients treated surgically for
      Maisonneuve fractures and to highlight factors associated with a suboptimal
      result. The authors present a review of 14 patients with Maisonneuve fractures.
      The mean age was 35.5 years. The most common injury mechanism was a twist
      incurred whilst participating in sport. The goal of treatment was the anatomic
      restoration of the ankle mortice with accurate renewal of fibular length. All
      patients had one or two suprasyndesmotic screws inserted percutaneously under
      fluoroscopic guidance. These were successfully removed under local anaesthesia in
      13 cases (93%). Patients were reassessed clinically and evaluated both
      functionally and radiographically. Average follow-up was 25.3 months. Twelve
      patients (86%) had a satisfactory result. They returned to previous activity
      levels and had favourable Global Foot and Ankle (mean: 95.57) and Shoe Comfort
      (mean: 81.66) Raw Scores. Ankle range of motion and radiographs were normal. Two
      patients had an unsatisfactory result. Surgical intervention is recommended to
      maintain reduction of the fibula into the notch on the tibia, as shortening
      results in mandatory lateral talar displacement, predisposing to painful ankle
      arthrosis. The severity of the initial injury and co-morbid disease may adversely
      affect outcome.

PMID- 15246804
TI  - Improvement in the treatment of stable ankle fractures: an audit based approach.
AB  - Stable ankle fracture patients form a distinct, clinically benign group in which
      functional treatment can be used. An initial retrospective audit of the fracture
      clinic records of our institution for 1 calendar year demonstrated that
      recognition and functional treatment of stable ankle fractures was rarely
      followed. After the introduction of formal departmental evidence-based
      guidelines, subsequent audits have showed progressive improvements with
      significant reductions of time spent immobilised in plaster, time spent non
      weight bearing and number of routine check radiographs, without compromising
      patient safety. This study illustrates the value of evidence-based guidelines in
      maintaining high standards of care over time.

PMID- 15246805
TI  - Weber B ankle fracture: an unnecessary fracture clinic burden.
AB  - Fifty-three patients with ankle fractures presenting to a trauma clinic at a busy
      district general hospital were used for this study. All subjects sustained
      fibular fractures at the syndesmosis without demonstrable medial instability or
      mortice incongruity. All cases were collected consecutively. Radiographs and case
      notes were studied for each patient. All fractures were categorised as Weber B
      [Pratique de l'osteosynthese. Les fractures malleolaires (1949)] without medial
      malleolar fracture. Data collected included the number of radiographs taken per
      patient and clinic reviews until discharge. Duration of immobilisation was
      recorded as well as weight bearing status. None of the 53 fractures showed any
      change in position following serial radiology. No patient underwent manipulation
      or internal fixation of the fracture. For Weber B fractures there was an average
      of six radiographs and 4.3 clinic reviews until discharge. There was a median
      time of 5.7 weeks spent in plaster immobilisation for these fractures. We
      conclude that once the decision is made to treat Weber B fractures as stable
      injuries they do not require regular review and serial radiographs. They require
      only one initial radiograph. Significant reductions in the number of trauma
      clinic consultations can be achieved as well as a national cost saving in the
      order of half a million pounds for the X-rays alone.

PMID- 15246806
TI  - Surgical reconstruction for chronic lateral instability of the ankle.
AB  - We have treated 56 patients (56 ankles) for symptomatic chronic lateral ankle
      instability by the surgical reconstruction procedure. The operation included
      lateral shift of the entire lateral capsule-ligament complex, suture to anterior
      border of fibula, and reinforcement by an elevated periosteal flap of distal
      fibula. These patients were reviewed at a mean period of 3.1 years (range, 9
      months to 5 years) after the operation. There were 29 males and 27 females with
      an average age of 29 years (range, 16-49 years). The clinical results were graded
      according to the AOFAS Ankle-Hindfoot scales. There were 35 patients who were
      excellent (above 90 points), 16 who were good (between 76 and 90 points), 4 who
      were fair (between 60 and 75 points), and 1 who was poor (below 60 points). The
      excellent and good results amounted to 91.1% (51/56). Therefore, we concluded
      that symptomatic chronic lateral ankle instability could be successfully managed
      with this easy and effective surgical reconstruction method.

PMID- 15246807
TI  - Instability of the tibio-fibular syndesmosis: have we been pulling in the wrong
      direction?
AB  - Syndesmotic stability in ankle fractures is usually assessed intraoperatively by
      pulling on the fibula with a bone hook in the coronal plane ("Hook Test"). Our
      clinical observations have suggested that instability may be more marked in the
      sagittal plane. Our aim was to compare movement at the tibio-fibular syndesmosis
      in the sagittal and coronal planes after sequential ligament division in a
      cadaver model. Seven specimens were used. The Hook Test was performed in both the
      sagittal and coronal planes. Movement was assessed by measuring the displacement
      of parallel k-wires. In all specimens, the anterior tibio-fibular, interosseous
      and posterior tibio-fibular ligaments were sequentially divided. In three
      specimens the deltoid ligament was then divided and the interosseous membrane in
      another three. After division of all three syndesmosis ligaments the mean
      displacement was 8.8 mm (+/-3.9) in the sagittal plane and 1.5 mm (+/-0.4) in the
      coronal plane. When the deltoid ligament was then divided, the displacement
      increased to 11.7 mm (+/-2.4) and 3.2 mm (+/-0.5), respectively. When the
      interosseous membrane was divided the measurements were 12.7 mm (+/-4) and 3.1 mm
      (+/-1.5). Movements were consistently greater in the sagittal plane than the
      coronal plane and we conclude that distal tibio-fibular instability should be
      assessed in the sagittal plane.

PMID- 15246809
TI  - Ankle sprain: an unexpected complication.
AB  - Blunt arterial injury is usually caused by high velocity trauma and can result in
      intimal dissection. We present a case of a professional footballer who sustained
      an intimal tear of the posterior tibial artery following a minor eversion injury
      of the ankle. The injury was noticed because of the physical demands of this
      patient's profession. This was confirmed by an arteriogram and was treated with
      bypass surgery using an arm vein. Arterial intimal injury has not been reported
      previously with this type of injury. A high index of suspicion is needed to
      diagnose these injuries and revascularisation either by primary anastomosis or
      vein interposition graft is suggested.

PMID- 15246808
TI  - Traumatic periprosthetic acetabular fracture: life threatening haemorrhage and a
      novel method of acetabular reconstruction.

PMID- 15246810
TI  - A complex distal femoral epiphyseal injury with a Hoffa's fracture.

PMID- 15246811
TI  - Cruciate fracture of the distal femur: the double Hoffa fracture.

PMID- 15246812
TI  - A displaced fracture of the neck of the radius with diaphyseal fracture of
      ipsilateral radius and ulna in a child.

PMID- 15246813
TI  - Segmental tibial fractures: an assessment of procedures in 27 cases.

PMID- 15246815
TI  - Abnormal inflammatory response to trauma: the paradoxical meaning of the
      ischaemia-reperfusion phenomenon.

PMID- 15246817
TI  - Dall-Miles plates for periprosthetic femoral fractures a critical review of 16
      cases.

PMID- 15246818
TI  - Ambiguity of estrogen receptor antagonists: good guys don't always wear white
      hats... or do they?

PMID- 15246819
TI  - Extending the window for acute stroke treatment: thrombolytics plus CNS
      protective therapies.

PMID- 15246820
TI  - Lost in translation: taking neuroprotection from animal models to clinical
      trials.
AB  - Caffeinol has been proposed as a neuroprotectant for human trials. This review
      covers a variety of animal models used and various attempts to take animal
      protocols to human trials. The accompanying paper discusses the rabbit model that
      was used to identify the efficacy of tissue plasminogen activator (tPA)
      treatment. To date, this is the only model that was able to achieve laboratory to
      clinical translational success. Use of caffeinol as a cytoprotective agent in rat
      models yielded exciting results, which led to clinical trials. However, caffeinol
      given with tPA in rabbits leads to increased hemorrhage. Caffeinol alone does not
      prove to be neuroprotective, as vasodilation by itself is not efficacious.
      However, vasodilation combined with thrombolysis (caffeinol with tPA) poses an
      increased risk of hemorrhage. For a more translational approach to study
      neuroprotection and neuroprotective agents in human trials, it is necessary to
      demonstrate the efficacy of the procedure and purported agents in several animal
      models.

PMID- 15246821
TI  - BMP signaling initiates a neural crest differentiation program in embryonic rat
      CNS stem cells.
AB  - Bone morphogenetic proteins (BMPs) have an important role in neuronal and
      astrocytic differentiation of embryonic and adult neural stem cells (NSCs). Here,
      we show that BMP6, BMP7, GDF5, and GDF6 instructively differentiate E12, E14, and
      E17 rat cortical NSCs into a variety of neural crest lineages. Clonal analysis
      shows that BMP7-treated NSCs develop mostly into smooth muscle and peripheral
      glia. We observed a rapid induction of premigratory neural crest markers like
      p75NTR, and AP-2 alpha followed by Msx1, Msx2, and Slug, transcription factors
      that participate in neural crest development. These results suggest that NSCs
      cultured in vitro in the presence of FGF2 display expanded developmental
      potential.

PMID- 15246822
TI  - The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in
      the hippocampus of adult mice.
AB  - The functions of presenilin 1 (PS1) and how PS1 mutations cause familial
      Alzheimer's disease (FAD) are incompletely understood. PS1 expression is
      essential for neurogenesis during embryonic development and may also influence
      neurogenesis in adult brain. We examined how increasing PS1 expression or
      expressing an FAD mutant would affect neurogenesis in the adult hippocampus. A
      neuron-specific enolase (NSE) promoter was used to drive neuronal overexpression
      of either wild-type human PS1 or the FAD mutant P117L in transgenic mice, and the
      animals were studied under standard-housing conditions or after environmental
      enrichment. As judged by bromodeoxyuridine (BrdU) labeling, neural progenitor
      proliferation rate was mostly unaffected by increasing expression of either wild
      type or FAD mutant PS1. However, in both housing conditions, the FAD mutant
      impaired the survival of BrdU-labeled neural progenitor cells leading to fewer
      new beta-III-tubulin-immunoreactive neurons being generated in FAD mutant animals
      during the 4-week postlabeling period. The effect was FAD mutant specific in that
      neural progenitor survival and differentiation in mice overexpressing wild-type
      human PS1 were similar to nontransgenic controls. Two additional lines of PS1
      wild-type and FAD mutant transgenic mice showed similar changes indicating that
      the effects were not integration site-dependent. These studies demonstrate that a
      PS1 FAD mutant impairs new neuron production in adult hippocampus by decreasing
      neural progenitor survival. They also identify a new mechanism whereby PS1 FAD
      mutants may impair normal neuronal function and may have implications for the
      physiological functioning of the hippocampus in FAD.

PMID- 15246823
TI  - Dietary sodium regulates angiotensin AT1a and AT1b mRNA expression in mouse
      brain.
AB  - Previous results showed that angiotensin (Ang) AT1a and AT1b receptor mRNA are
      expressed in mouse hypothalamus (HYP), brainstem (BS) and anterior pituitary
      (PIT). To extend these findings, we developed a real-time polymerase chain
      reaction (PCR) method to differentiate and quantify Ang AT1a and AT1b mRNA in
      mouse brain. An experiment was conducted in male C57Bl/6J mice to determine the
      effects of low and high dietary salt (0.04 or 8% NaCl for 2 weeks) on mRNA
      expression. Physiological measurements showed that high salt increased water
      intake (15.1 +/- 0.6 ml/day), whereas low salt decreased water intake (3.2 +/-
      0.1 ml/day). There were no significant changes in body weight, hematocrit or
      plasma osmolality. Real-time PCR was effective in distinguishing AT1a and AT1b
      receptor mRNA. The PCR efficiencies for AT1a, AT1b and 18S ribosome were tested
      to be identical, making it possible to quantify mRNA levels. There were
      differences in angiotensin receptor expression, related to diet and brain region.
      In hypothalamus, both the high salt and low salt diet decreased AT1a expression
      (to 63 +/- 4% and 62 +/- 1%), although there were no changes in AT1b. In
      brainstem, there was a marked increase in AT1a (to 365 +/- 60%) and AT1b (to 372
      +/- 23%) after high salt, although there was only a marked decrease for AT1b (to
      23 +/- 5%) after low salt. In anterior pituitary, both high salt and low salt
      diet increased AT1a expression (to 152 +/- 8% and 123 +/- 9%), although there
      were no changes in AT1b. Results document that both AT1 receptor subtypes are
      present in mouse hypothalamus, brainstem and anterior pituitary, and that there
      is differential regulation of expression in response to changes in dietary salt.

PMID- 15246824
TI  - Activation of c-Jun N-terminal kinase mediates gp120IIIB- and nucleoside analogue
      induced sensory neuron toxicity.
AB  - Peripheral neuropathy is the most common neurological symptom in patients with
      acquired immunodeficiency syndrome (AIDS). Here, we examine possible mechanisms
      of gp120 and nucleoside reverse transcriptase inhibitors (NRTIs) in the
      pathogenesis of AIDS peripheral neuropathy. Neonatal dorsal root ganglion (DRG)
      neurons were found to undergo apoptosis in response to chronic treatment with
      gp120IIIB, an effect enhanced by the co-application of hCD4, as well as upon
      exposure to the nucleoside reverse transcriptase inhibitor (NRTI), 2',3'
      dideoxyinosine (ddI). DRG neurons were rescued from the neurotoxic effects of
      these agents by CEP-1347, an inhibitor of the mixed lineage kinases (MLKs),
      upstream activators of the c-Jun N-terminal kinase (JNK) signaling pathway. In
      addition, gp120- or ddI-mediated toxicity were also inhibited by neuronal
      expression of dominant negative versions of the MLKs. Our results suggest that
      both gp120 and the NRTIs cause sensory neuron apoptosis through the activation of
      the JNK pathway, and that CEP-1347-like compounds may serve as a therapeutic
      option in patients with AIDS-associated peripheral neuropathy.

PMID- 15246825
TI  - Fate of cloned embryonic neuroectodermal cells implanted into the adult, newborn
      and embryonic forebrain.
AB  - NE-4C, one-cell derived neuroectodermal stem cells expressing a reporter gene-
      green fluorescent protein (GFP) or heat-resistant alkaline phosphatase (PLAP)--or
      prelabeled with bromodeoxyuridine (BrdU) were implanted into the forebrain of
      adult, new-born and fetal mice and into the mid- and forebrain vesicles of early
      chick embryos. The fate of implanted cells in the mouse and chick hosts was
      followed up to 6 and 2 weeks, respectively. Neural differentiation was monitored
      by detecting the expression of neuron-specific markers and GFAP. NE-4C cells
      integrated into the early embryonic brain tissue and developed into
      morphologically differentiated neurons. The same cells produced expanding tumor
      like aggregates in the newborn forebrain and were expelled from the adult
      forebrain parenchyma. In the adult brain, long-term survival and integration of
      stem cells were revealed only in neurogenic zones. The data suggest that
      noncommitted, proliferating neuroectodermal progenitors can integrate into the
      brain tissue at time and site of tissue genesis.

PMID- 15246826
TI  - Impact of the selective estrogen receptor modulator, tamoxifen, on neuronal
      outgrowth and survival following toxic insults associated with aging and
      Alzheimer's disease.
AB  - We investigated the estrogen agonist/antagonist properties of the selective
      estrogen receptor modulators (SERMs), tamoxifen (TMX) and 4-hydroxy-tamoxifen
      (OHT), using an in vitro neuron model system to determine the impact of the
      neuroprotective and neurotrophic properties of these SERMs. Low concentrations of
      TMX or OHT were without effect on a marker of neuronal viability, basal release
      of lactate dehydrogenase (LDH), whereas high concentrations of both SERMs (2500
      ng/ml) induced a significant increase in LDH, indicating the potential toxicity
      of both SERMs at high concentrations. Subsequent experiments revealed that
      subtoxic concentrations of both TMX and OHT induced significant neuroprotection
      against beta-amyloid(25-35)-induced toxicity; 15-20% and 10-15% (P < 0.05),
      respectively and also against glutamate-induced toxicity; 25-30% and 20-40% (P <
      0.05 and P < 0.01), respectively. Additional in vitro experiments included
      analysis of neuron survival to determine whether the SERM, OHT, acted
      competitively or synergistically with the endogenous estrogen, 17 beta-estradiol
      (E2). These revealed that neuron survival following exposure to the neurotoxins
      beta-amyloid and excitotoxic glutamate was significantly increased in cultures
      treated with OHT (50 ng/ml) (10%, P < 0.01) and that the magnitude of survival
      was equivalent to E2 (10 ng/ml). The combined presence of OHT and E2
      significantly protected against both beta-amyloid(25-35) and excitotoxic
      glutamate-induced neuron death (10%, P < 0.01) but was not significantly
      different from either OHT or E2 alone. To assess neurotrophic effects of these
      same SERMs, cultured neurons from brain regions involved in memory function and
      Alzheimer's disease were evaluated by morphological analysis of individual
      neurons. Results of these analyses demonstrated that TMX treatment did not
      significantly increase the process outgrowth or morphological complexity of
      cortical, hippocampal, or basal forebrain neurons. Similar analyses showed that
      OHT also failed to significantly increase the neuronal outgrowth of either
      cortical or hippocampal neurons. Results of these studies predict that TMX and
      OHT could exert a neuroprotective function but would not promote estrogen
      dependent memory function.

PMID- 15246827
TI  - Coadministration of NXY-059 and tenecteplase six hours following embolic strokes
      in rabbits improves clinical rating scores.
AB  - Currently, the only FDA-approved treatment for acute ischemic stroke (AIS) is the
      thrombolytic, tissue plasminogen activator (tPA; alteplase; activase). It has
      been proposed that both the spin trap agent NXY-059 (cerovive) and tenecteplase
      (TNK-tPA), which are currently in phase II clinical trials, may also be useful
      for the treatment of ischemic stroke. However, there is little information
      available concerning the dose-response profiles or therapeutic window for NXY-059
      in a validated embolic stroke model, nor is there information available
      pertaining to the effects of combining NXY-059 with tenecteplase. Thus, we
      determined the pharmacological profile of NXY-059 on behavioral outcome following
      small clot embolic strokes in rabbits when administered alone or in combination
      with tenecteplase. Male New Zealand white rabbits were embolized by injecting a
      suspension of small blood clots into cerebral circulation via a carotid catheter.
      NXY-059 (0.1-100 mg/kg) was infused intravenously (IV), 1 h following
      embolization, whereas control rabbits received infusions of saline. We also
      determined the therapeutic window for NXY-059 by administering the drug 1, 3, or
      6 h following embolic strokes. Lastly, in combination studies, NXY-059 was given
      concomitantly with tenecteplase 1 or 6 h following embolization. In the vehicle
      control group, the P(50) value (milligrams of clots that produce behavioral
      deficits in 50% of the rabbits) measured 24 h following embolism was 1.20 +/-
      0.15 mg, and this was increased by 100-134% if NXY-059 (1-100 mg/kg) was
      administered following embolization. If NXY-059 was administered beginning 3 or 6
      h following embolization, there was no significant behavioral improvement. If NXY
      059 (100 mg/kg) and tenecteplase (0.9 mg/kg) were administered concomitantly 1 h
      postembolization, we did not measure any additional behavioral improvement
      compared to either drug alone. However, if the drugs were administered 6 h
      following embolization, we measured a statistically significant reduction of
      behavioral deficits. This study shows that NXY-059 is neuroprotective over a wide
      range if administered early following an embolic stroke. In addition, the study
      shows that NXY-059 can be administered in combination with tenecteplase to
      provide additional behavioral improvement at extended delays following
      embolization.

PMID- 15246828
TI  - Pharmacology of caffeinol in embolized rabbits: clinical rating scores and
      intracerebral hemorrhage incidence.
AB  - Caffeinol is currently being tested in acute ischemic stroke patients. However,
      little is known about the pharmacology or safety of caffeinol in preclinical
      embolic stroke models. We determined the pharmacological effects of caffeinol
      administration on clinical rating scores in rabbits following small clot embolic
      strokes (RSCEM). Male New Zealand white rabbits were embolized by injecting blood
      clots into the cerebral circulation via a carotid catheter. Behavioral analysis
      was conducted 24 h following embolization, allowing for the determination of the
      effective stroke dose (P50) or clot amount (mg) that produces neurological
      deficits in 50% of the rabbits. In the current study, the P50 values for the
      control groups were 1.32 +/- 0.23 and 1.66 +/- 0.29 mg for the bolus-injected and
      infused groups, respectively. Rabbits treated with caffeinol (bolus) starting 15
      min following embolization had a P50 value of 1.70 +/- 1.18 mg. Caffeinol-infused
      rabbits had a P50 value of 2.05 +/- 0.47 and 1.67 +/- 0.48 mg for low- and high
      dose ethanol, respectively. In tPA-treated rabbits (0.9 mg/kg), the group P50 was
      1.58 +/- 0.43 mg. In caffeinol (bolus) and tPA-treated rabbits, we measured a
      decrease in the P50 value to 0.70 +/- 0.30 mg and an increase in the rate of
      intracerebral hemorrhage compared to control. This primary finding of this study
      indicates that neither bolus-injected nor infused caffeinol affects behavioral
      deficits following embolic strokes in rabbits. Moreover, the combination of
      caffeinol plus low-dose tPA does not improve behavioral deficits. However, our
      study suggests that there is the potential for exacerbation of stroke-induced
      behavioral deficits following caffeinol administration in combination with a
      thrombolytic that may be related to increased intracerebral hemorrhage.

PMID- 15246829
TI  - Treatment with immunosuppressive and anti-inflammatory agents delays onset of
      canine genetic narcolepsy and reduces symptom severity.
AB  - All Doberman pinschers and Labrador retrievers homozygous for a mutation of the
      hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal
      conditions. Degenerative changes and increased display of major
      histocompatibility complex class II antigens have been linked to symptom onset in
      genetically narcoleptic Doberman pinschers. This suggests that the immune system
      may contribute to neurodegenerative changes and narcoleptic symptomatology in
      these dogs. We therefore attempted to alter the course of canine genetic
      narcolepsy, as an initial test of principle, by administering a combination of
      three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune
      response globally. Experimental dogs were treated with a combination of
      methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks
      after birth, and raised in an environment that minimized pathogen exposure.
      Symptoms in treated and untreated animals were quantified using the food elicited
      cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to
      cataplexy onset more than doubled, time spent in cataplexy during tests was
      reduced by more than 90% and nighttime sleep periods were consolidated. Short
      term drug administration to control dogs did not reduce cataplexy symptoms,
      demonstrating that the drug regimen did not directly affect symptoms. Treatment
      was stopped at 6 months, after which experimental animals remained less
      symptomatic than controls until at least 2 years of age. This treatment is the
      first shown to affect symptom development in animal or human genetic narcolepsy.
      Our findings show that hcrtr2 mutation is not sufficient for the full symptomatic
      development of canine genetic narcolepsy and suggest that the immune system may
      play a role in the development of this disorder.

PMID- 15246830
TI  - Interaction of transplanted olfactory-ensheathing cells and host astrocytic
      processes provides a bridge for axons to regenerate across the dorsal root entry
      zone.
AB  - A single fourth lumbar dorsal rootlet was transected at the entry point into the
      spinal cord. The nerve fibres were labelled with biotin dextran injected into the
      rootlet. An endogenous matrix containing olfactory-ensheathing cells (OECs)
      labelled with green fluorescent protein was applied to the opposing cut surfaces
      of the rootlet and the spinal cord, which were then brought into apposition and
      held in place by fibrin glue. Two weeks later, a ladderlike bridging structure
      has been formed by astrocytic processes growing out for about 200-300 microm from
      the spinal cord. The transplanted cells remained largely confined to this area.
      They were elongated along the nerve axis but did not enter the spinal cord
      itself. Labelled dorsal root axons crossed the repaired dorsal root entry zone in
      alignment with the bridging astrocytic processes and the transplanted cells and
      then proceeded beyond the transplant to enter the grey matter of the dorsal horn
      and send axons both rostrally and caudally for at least 10 mm in the white matter
      of the ascending dorsal columns.

PMID- 15246831
TI  - Perineuronal nets potentially protect against oxidative stress.
AB  - A specialized form of extracellular matrix (ECM) termed perineuronal nets (PNs)
      consisting of large aggregating chondroitin sulfate proteoglycans (CSPGs), with
      hyaluronan and tenascin as main components, surrounds subpopulations of neurons.
      The glycosaminoglycan components of perineuronal nets form highly charged
      structures in the direct microenvironment of neurons and thus might be involved
      in local ion homeostasis. The polyanionic character suggests that perineuronal
      nets also potentially contribute to reduce the local oxidative potential in the
      neuronal microenvironment by scavenging and binding redox-active iron, thus
      providing some neuroprotection to net-associated neurons. Here, we show that
      neurons ensheathed by a perineuronal net in the human cerebral cortex are less
      frequently affected by lipofuscin accumulation than neurons without a net both in
      normal-aged brain and Alzheimer's disease (AD). As lipofuscin is an
      intralysosomal pigment composed of cross-linked proteins and lipids generated by
      iron-catalyzed oxidative processes, the present results suggest a neuroprotective
      function of perineuronal nets against oxidative stress, potentially involved in
      neurodegeneration.

PMID- 15246832
TI  - Radiation-induced impairment of hippocampal neurogenesis is associated with
      cognitive deficits in young mice.
AB  - Advances in the management of pediatric brain tumors have increased survival
      rates in children, but their quality of life is impaired due to cognitive
      deficits that arise from irradiation. The pathogenesis of these deficits remains
      unknown, but may involve reduced neurogenesis within the hippocampus. To
      determine the acute radiosensitivity of the dentate subgranular zone (SGZ), 21
      day-old C57BL/J6 male mice received whole brain irradiation (2-10 Gy), and 48 h
      later, tissue was assessed using immunohistochemistry. Proliferating SGZ cells
      and their progeny, immature neurons, were decreased in a dose-dependent fashion.
      To determine if acute changes translated into long-term alterations in
      neurogenesis, mice were given a single dose of 5 Gy, and 1 or 3 months later,
      proliferating cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Confocal
      microscopy was used to determine the percentage of BrdU-labeled cells that showed
      mature cell phenotypes. X-rays significantly reduced the production of new
      neurons at both time points, while glial components showed no change or small
      increases. Measures of activated microglia and infiltrating, peripheral monocytes
      indicated that reduced neurogenesis was associated with a chronic inflammatory
      response. Three months after irradiation, changes in neurogenesis were associated
      with spatial memory retention deficits determined using the Morris water maze.
      Behavioral training and testing increased the numbers of immature neurons, most
      prominently in irradiated animals. These data provide evidence that irradiation
      of young animals induces a long-term impairment of SGZ neurogenesis that is
      associated with hippocampal-dependent memory deficits.

PMID- 15246833
TI  - Axonal reinjury reveals the survival and re-expression of regeneration-associated
      genes in chronically axotomized adult mouse motoneurons.
AB  - Recently, we reported that chronically axotomized rubrospinal neurons survive for
      up to 1 year in an atrophied state. This finding contrasted previous work
      suggesting the death of up to 50% of the neurons over time. In the adult mouse,
      the majority of facial motoneurons appear to be lost as a result of chronic nerve
      resection. Here, we sought to determine if chronically resected adult mouse
      facial motoneurons, like rubrospinal neurons, survive in an atrophied state. To
      test this hypothesis, we asked whether a second nerve injury, 10 weeks after an
      initial nerve resection, could stimulate a regenerative cell body response. After
      chronic resection (10 weeks), mouse facial motoneurons underwent atrophy
      resulting in a loss of countable neuronal cell bodies. In addition, the
      motoneurons failed to maintain their initial increase in expression of GAP-43 and
      alpha-tubulin mRNA. Reinjury of 10-week chronically resected facial motoneurons
      by the removal of the neuroma reversed the atrophy of the cell bodies and
      increased the percentage of identifiable cell bodies from 36% of contralateral to
      79% in C57BL/6-C3H mice and from 28% of contralateral to 40% in Balb/c mice.
      Moreover, the reinjured motoneurons displayed an increase in GAP-43 and alpha
      tubulin mRNA expression. The results of this study indicate that a second axon
      injury stimulates regenerative cell body responses in chronically resected mouse
      facial motoneurons and suggest previous studies using this model may have
      overestimated the number of dying motoneurons.

PMID- 15246834
TI  - Nitric oxide production and regulation of neuronal NOS in tyrosine hydroxylase
      containing neurons.
AB  - CAD cells are a murine CNS catecholaminergic (tyrosine hydroxylase-positive; TH+)
      neuronal cell line that undergoes morphological differentiation to resemble CNS
      catecholaminergic neurons upon serum deprivation. We show here that CAD cells
      also express neuronal nitric oxide synthase (nNOS) mRNA and protein and produce
      readily measurable levels of NO. Since both NO and catecholamines (L-DOPA;
      dopamine; norepinephrine) are redox active molecules, their production within the
      same cell may affect the cell's vulnerability to insult. Thus, we examined the
      regulation of NO production by CAD cells and the effect of NO on cell survival.
      NO is generated in a dose-dependent fashion by treatment with agents (ionomycin;
      A23817; KCl) known to increase calcium entry across the cell membrane. The NO
      level can be increased further by pretreatment with sepiapterin, a membrane
      permeable precursor for BH4 synthesis, suggesting that the BH4 levels or access
      required for nNOS activation is limited in CAD cells. Reducing mitochondrial Ca2+
      uptake using ruthenium red (RuR) increased ionomycin-mediated NO production over
      ionomycin alone and indicates a critical role for mitochondria in nNOS
      regulation. Cell death was significantly increased by ionomycin treatment alone
      or in conjunction with reduced mitochondrial Ca2+ uptake. However, NO was not the
      primary mediator of cell death since NOS inhibitors rescued only less than 10% of
      the cells. These data suggest that endogenous NO production by nNOS is not a
      major factor in CAD cell death under these conditions.

PMID- 15246835
TI  - Serotonin neurons derived from rhesus monkey embryonic stem cells: similarities
      to CNS serotonin neurons.
AB  - We sought an in vitro primate model for serotonin neurons. Rhesus monkey
      embryonic stem (ES) cell colonies were isolated and differentiated into embryoid
      bodies (EBs), then transferred to serum-free medium with 1% insulin-transferrin
      selenium for 7 days to induce neural precursor cell (NPC) formation. NPCs were
      cultured in medium with 1% N-2 neural supplement and human fibroblast growth
      factor 2 (FGF2, 10 ng/ml) for 7 days to stimulate cell proliferation. Lastly,
      NPCs were dispersed into single cells and cultured without FGF2 for another 7
      days to obtain terminal differentiation. Terminal cells were characterized for
      neuronal and serotonergic markers. Over 95% of the NPCs were immunopositive for
      nestin and Musashi1. Terminally differentiated cells appeared in both small and
      large morphologies. Most (>95%) of the mature cells (both small and large) were
      immunopositive for neuron-specific nuclear protein (NeuN), synaptophysin,
      microtubule-associated protein (MAP2C), Tau-1, neurofilament 160 (NF-160), beta
      tubulin (TujIII), tryptophan hydroxylase (TPH), serotonin, the serotonin reuptake
      transporter (SERT), estrogen receptor-beta (ERbeta), and progestin receptor (PR),
      but not estrogen receptor-alpha (ERalpha). Less than 2-3% of cells were positive
      for tyrosine hydroxylase (TH). Reverse transcriptase polymerase chain reaction
      (RT-PCR) detected mRNA transcripts for TPH-1, TPH-2, SERT, 5-HT1A-autoreceptor,
      ERbeta, and PR in the differentiated population. A low level of expression of
      ERalpha mRNA was also detected. Quantitative RT-PCR indicated that the relative
      abundance of TPH-2 mRNA was greater than TPH-1 mRNA. Serotonin as measured by
      ELISA increased 3-fold in the mature stage compared to the selection and
      expansion stages. In summary, a remarkably high percentage of cells derived from
      monkey ES cells exhibited neuronal plus serotonergic markers as well as nuclear
      steroid receptors similar to primate CNS serotonin neurons, suggesting that these
      cells may serve as a useful primate model for serotonergic neurons.

PMID- 15246836
TI  - Sodium channel blockade with phenytoin protects spinal cord axons, enhances
      axonal conduction, and improves functional motor recovery after contusion SCI.
AB  - Accumulation of intracellular sodium through voltage-gated sodium channels
      (VGSCs) is an important event in the cascade leading to anatomic degeneration of
      spinal cord axons and poor functional outcome following traumatic spinal cord
      injury (SCI). In this study, we hypothesized that phenytoin, a sodium channel
      blocker, would result in protection of axons with concomitant improvement of
      functional recovery after SCI. Adult male Sprague-Dawley rats underwent T9
      contusion SCI after being fed normal chow or chow containing phenytoin; serum
      levels of phenytoin were within therapeutic range at the time of injury. At
      various timepoints after injury, quantitative assessment of lesion volumes,
      axonal degeneration, axonal conduction, and functional locomotor recovery were
      performed. When compared to controls, phenytoin-treated animals demonstrated
      reductions in the degree of destruction of gray and white matter surrounding the
      lesion epicenter, sparing of axons within the dorsal corticospinal tract (dCST)
      and dorsal column (DC) system rostral to the lesion site, and within the
      dorsolateral funiculus (DLF) caudal to the lesion site, and enhanced axonal
      conduction across the lesion site. Improved performance in measures of skilled
      locomotor function was observed in phenytoin-treated animals. Based on these
      results, we conclude that phenytoin provides neuroprotection and improves
      functional outcome after experimental SCI, and that it merits further examination
      as a potential treatment strategy in human SCI.

PMID- 15246837
TI  - Glycogen synthase kinase 3beta inhibitor Chir025 reduces neuronal death resulting
      from oxygen-glucose deprivation, glutamate excitotoxicity, and cerebral ischemia.
AB  - The serine/threonine kinase, glycogen synthase kinase 3beta (GSK3beta), is
      abundant in CNS and is neuron specific. GSK3beta plays a pivotal role in the
      regulation of numerous cellular functions. GSK3beta phosphorylates and thereby
      regulates many metabolic, signaling, and structural proteins which can influence
      cell survival. Increased GSK3beta correlates with increased cell death, whereas
      reduced GSK3beta expression correlates with increased cell survival. We report
      that the GSK3beta inhibitor Chir025 is neuroprotective in vitro and in vivo.
      First, Chir025 reduced cultured hippocampal neuron death following glutamate
      exposure by 15-20% versus vehicle-treated controls. Second, Chir025 significantly
      reduced cultured cortical neuron death following oxygen-glucose deprivation (OGD)
      by approximately 50%. Third, Chir025 reduced infarct size following focal
      cerebral ischemia by nearly 20%. There were no significant differences in the
      number of TUNEL-positive neurons or in caspase-3 and -9 activities between
      Chir025- and vehicle-treated rats, although Chir025 elevated cytosolic Bcl-2
      expression. These data show that Chir025-mediated inhibition of GSK3beta is
      neuroprotective and that the mechanism is probably not anti-apoptotic.

PMID- 15246838
TI  - Differential effects of scopolamine on in vivo binding of dopamine transporter
      and vesicular monoamine transporter radioligands in rat brain.
AB  - The in vivo equilibrium specific binding of d-threo-[3H]methylphenidate, a
      radioligand for the dopamine transporter (DAT), and +-alpha
      [3H]dihydrotetrabenazine, a radioligand for the vesicular monoamine transporter
      (VMAT2), were examined in rat brain with and without prior administration of 5
      mg/kg scopolamine. Drug-treated animals exhibited a 30% increase in d-threo
      [3H]methylphenidate binding to the DAT in the striatum relative to controls. No
      changes in specific binding of +-alpha-[3H]dihydrotetrabenazine were observed in
      any brain region following scopolamine pretreatment. Cholinergic drugs thus
      differentially affect in vivo specific binding of DAT and VMAT2 radioligands,
      suggesting this should be a consideration in selection of in vivo markers for
      imaging studies of dopaminergic terminals in the brain of animals and humans.

PMID- 15246839
TI  - Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord
      of the adult mouse.
AB  - Injury in the peripheral or central nervous systems causes a significant rise in
      the levels of the pleiotropic cytokine leukemia inhibitory factor (LIF). This
      increase influences cell survival, reactive gliosis and inflammatory responses.
      Since prior work has focused primarily on peripheral nerve and brain, little is
      known about the role of LIF in the spinal cord injury response. We address this
      issue by examining the effects of injury in the LIF knockout (KO) mouse, as well
      as using an adenoviral vector to over-express LIF in the spinal cord of adult
      mice. We find that LIF over-expression results in a dramatic rise in cell
      proliferation, primarily in microglia/macrophages. Astrocytes are not stimulated
      to proliferate but are activated by the elevated LIF. LIF over-expression also
      causes the development of severe hindlimb motor dysfunction, an effect mediated
      by the enhanced activation of microglia/macrophages, as inhibiting microglial
      activation with minocycline attenuates these motor deficits. Conversely,
      proliferation is significantly diminished and the microglial/macrophage response
      to spinal cord injury is much less in the LIF KO compared to wild type (WT).
      Thus, LIF is a potent pro-inflammatory factor in the adult spinal cord and
      represents a potential target for the manipulation of inflammatory reactions
      after spinal cord injury.

PMID- 15246840
TI  - Heparin stabilizes FGF-2 and modulates striatal precursor cell behavior in
      response to EGF.
AB  - Fibroblast and epidermal growth factors (FGF-2 and EGF) are powerful mitogens for
      neural precursor cells isolated from the developing striatum and grown as
      neurospheres. However, questions remain as to the exact role of each of these
      molecules, and how the proteoglycan heparin may modify their behavior. Here, we
      show that FGF-2 is remarkably unstable in culture media, but that heparin could
      completely prevent its degradation, which led to faster cell growth rates. In
      addition, heparin significantly increased the number of cells within the E14
      striatum responding to a brief pulse of FGF-2. In contrast, EGF was unable to
      stimulate the growth of E14 striatal precursors. However, EGF could induce the
      division of E18 striatal precursors as neurospheres and acted synergistically
      with FGF-2. FGF-2/heparin neurospheres generated significantly more neurons than
      EGF neurospheres. Interestingly, the addition of heparin to EGF neurospheres,
      which had no effects on EGF stability or growth rates, increased the numbers of
      neurons generated to that seen for FGF-2/heparin neurospheres. EGF neurospheres
      were found to produce FGF-2, but addition of heparin did not affect its
      concentration within cells or in the medium suggesting this released FGF-2 may
      already be bound to a proteoglycan. In addition, expanding cells with EGF plus
      heparin in the presence of an FGF-2 blocker did not have a significant effect on
      the number of neurons generated confirming that the increase in neuronal number
      is through a mechanism which is independent of FGF-2.

PMID- 15246841
TI  - Activation of cell death pathway after a brief period of global ischemia in
      diabetic and non-diabetic animals.
AB  - Mitochondria play a critical role in the pathogenesis of cerebral ischemia. Acute
      hyperglycemia has been shown to activate the mitochondria-initiated cell death
      pathway after an intermediate period of ischemia. The objective of the present
      study was to determine if diabetic hyperglycemia induced by streptozotocin
      activates the cell death pathway after a brief period of global ischemia. Five
      minutes of global ischemia was induced in nondiabetic and diabetic rats. Brain
      samples were collected after 30 min, 6 h, 1, 3, and 7 days of recirculation as
      well as from sham-operated controls. Histopathological examination in the
      hippocampal CA1, CA3, hilus, and dentate gyrus regions, as well as in the
      cortical and thalamic areas, showed that neuronal death in diabetic animals
      increased compared to nondiabetic ischemic controls. Neuronal damage maturation
      occurred after 7 days of recovery in nondiabetic rats, while it was shortened to
      3 days of recovery in diabetic animals. Western blot analyses revealed that
      release of cytochrome c markedly increased after 1 and 3 days of reperfusion in
      diabetic rats. Caspase-3 activation was evident in the nuclear fraction of the
      cortex of diabetic rats after 3 days recovery and it was preceded by activation
      of caspase-9, but not activation of caspase-8. Electron microscopy demonstrated
      that chromatin condensation and mitochondrial swelling were features of the
      diabetes-mediated ischemic neuronal damage. However, no apoptotic bodies were
      observed in any sections examined. These results suggest that a brief period of
      global ischemia in diabetic animals activates a neuronal cell death pathway
      involving cytochrome c release, caspase-9 activation, and caspase-3 cleavage, all
      of which are most likely initiated by early mitochondria damage.

PMID- 15246842
TI  - Basal ganglia--hippocampal interactions support the role of the hippocampal
      formation in sensorimotor integration.
AB  - Experiments were carried out to evaluate whether neural activity in the basal
      ganglia is functionally related to the neural activity underlying mechanisms of
      theta band oscillation and synchrony in the hippocampal formation. Experiment 1
      demonstrated that electrical stimulation administered to the substantia nigra,
      globus pallidus (GP) and caudate-putamen (CPu) in urethane anesthetized rats
      elicited theta field activity in the hippocampal formation. Subsequent
      microinfusion of the local anesthetic procaine hydrochloride into the medial
      septum reversibly abolished this effect. In Experiment 2, single cell discharge
      profiles established for 152 cells recorded in nuclei of the basal ganglia
      resulted in 101 (66%) being classified as theta-related and 51 (34%) classified
      as nonrelated. Theta-related cells were further subclassified as tonic theta-ON
      cells (n = 79) and tonic theta-OFF (n = 22). Tonic theta-ON and tonic theta-OFF
      cells displayed irregular or regular (tonic) discharge patterns. Rhythmic
      discharge patterns did not occur in any theta-related cells in the nuclei of the
      basal ganglia. However, analyses using Kaneoke and Vitek's [J. Neurosci. Methods
      68, (1996) 211] algorithms revealed that 51/101 (50%) theta-related cells
      displayed periodicity in their discharge patterns whereas 27/51 (53%) of the
      nonrelated cells displayed periodicity in their discharge patterns. The
      periodicities in the majority of cells were in frequency ranges above that of
      theta band oscillation and synchrony. The results support the following
      conclusions: (1) the cellular activity of the basal ganglia, composed of nuclei
      traditionally associated with motor functions, is functionally connected with the
      neural circuitry involved in the generation of theta band oscillation and
      synchrony in the hippocampal formation; (2) the observed functional connectivity
      provides support for the role of the hippocampal formation in sensorimotor
      integration.

PMID- 15246843
TI  - Partial sciatic nerve transection causes redistribution of pain-related peptides
      and lowers withdrawal threshold.
AB  - Complete nerve transection results in loss of sensation and paralysis of the
      involved extremity. Such injury drastically reduces content of the nociceptive
      peptides, substance P, and somatostatin in the dorsal horn of the spinal cord and
      dorsal root ganglia innervating the limb. Partial nerve injuries occur more
      commonly in clinical practice, however, and frequently result in the development
      of chronic neuropathic pain. To investigate mechanisms underlying this pathologic
      pain syndrome, rats were subjected to partial sciatic nerve transection.
      Withdrawal thresholds determined with Von Frey hairs dropped dramatically in the
      operated limb. On postoperative Day 4, thresholds had decreased from 15 g to less
      than 5 g on the operated side, whereas those on the contralateral (unoperated)
      side or those from sham-operated rats did not change. Sciatic hemisection had no
      effect on total content of either substance P or somatostatin in the dorsal
      spinal cord and lumbar dorsal root ganglia as measured by radioimmunoassay on
      postoperative Days 4, 7, or 14. However, when examined immunohistochemically,
      there was a marked redistribution of both peptides associated with partial
      transection. On the contralateral side or in sham-operated rats, both substance P
      and somatostatin were confined to the superficial laminae of the dorsal horn. By
      contrast, on the operated side, content of both peptides was reduced by more than
      half in the superficial laminae. There was a compensatory increase in content in
      the deeper laminae where nociceptive peptides are not usually found.
      Redistribution of substance P and somatostatin may be due to axonal sprouting,
      increased peptide expression by interneurons, or aberrant expression of
      nociceptive peptides by neurons normally mediating mechanical sensation. The
      presence of increased levels of nociceptive peptides in regions of the spinal
      cord that mediate innocuous sensation may underlie development of allodynia.

PMID- 15246844
TI  - Modifications of local cerebral glucose utilization in thalamic structures
      following injection of a dopaminergic agonist in the nucleus accumbens-
      involvement in antiepileptic effects?
AB  - Dopaminergic transmission in the nucleus accumbens (NAcc) is implicated in
      different aspects of reward and motivational mechanisms. More recently, it has
      been suggested that this nucleus could also be involved in the modulation of
      generalized epileptic seizures. In particular, microinjection of dopaminergic
      agonists in the NAcc suppresses the occurrence of epileptic seizures in a model
      of absence seizures, the GAERS (generalized absence epileptic rats from
      Strasbourg). The aim of this study was to identify the structures involved in
      this effect. Local cerebral metabolic rates for glucose utilization (LCMRglc)
      were measured in different parts of the basal ganglia and output structures after
      apomorphine injection in the NAcc in GAERS and in the inbred non-epileptic rats
      (NE), concomitantly with seizure suppression. Apomorphine injection in the NAcc
      induced a significant increase of glucose intake in the anteromedial, mediodorsal
      and ventrolateral nuclei of the thalamus in NE rats, while no significant changes
      were observed in the basal ganglia structures (globus pallidus, subthalamic
      nucleus, substantia nigra). Furthermore, microinjections of muscimol (100 and 200
      pmol/side) in the mediodorsal nucleus of the thalamus in GAERS rats suppressed
      seizures. These results suggest that the mediodorsal nucleus of the thalamus
      could be involved in absence seizures modulation. Along with data from the
      literature, our data suggest that this nucleus could participate in the control
      of the basal ganglia over generalized epileptic seizures.

PMID- 15246845
TI  - Cholinesterase inhibitors modify the activity of intrinsic cardiac neurons.
AB  - Cholinesterase inhibitors used to treat the symptoms of Alzheimer's disease (AD)
      inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE),
      albeit to different degrees. Because central and peripheral neurons, including
      intrinsic cardiac neurons located on the surface of the mammalian heart, express
      both BuChE and AChE, we studied spontaneously active intrinsic cardiac neurons in
      the pig as a model to assess the effects of inhibition of AChE compared to BuChE.
      Neuroanatomical experiments showed that some porcine intrinsic cardiac neurons
      expressed AChE and/or BuChE. Enzyme kinetic experiments with cholinesterase
      inhibitors, namely, donepezil, galantamine, (+/-) huperzine A, metrifonate,
      rivastigmine, and tetrahydroaminoacridine, demonstrated that these compounds
      differentially inhibited porcine AChE and BuChE. Donepezil and (+/-) huperzine A
      were better reversible inhibitors of AChE, and galantamine equally inhibited both
      the enzymes. Tetrahydroaminoacridine was a better reversible inhibitor of BuChE.
      Rivastigmine caused more rapid inactivation of BuChE as compared to AChE.
      Neurophysiological studies showed that acetylcholine and butyrylcholine increase
      or decrease the spontaneous activity of the intrinsic cardiac neurons. Donepezil,
      galantamine, (+/-) huperzine A, and tetrahydroaminoacridine changed spontaneous
      neuronal activity by about 30-35 impulses per minute, while rivastigmine changed
      it by approximately 100 impulses per minute. It is concluded that (i) inhibition
      of AChE and BuChE directly affects the porcine intrinsic cardiac nervous system,
      (ii) the intrinsic cardiac nervous system represents a suitable model for
      examining the effects of cholinesterase inhibitors on mammalian neurons in vivo,
      and (iii) the activity of intrinsic cardiac neurons may be affected by
      pharmacological agents that inhibit cholinesterases.

PMID- 15246846
TI  - The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates L-DOPA-induced
      dyskinesia and provides mild potentiation of anti-parkinsonian effects of L-DOPA
      in the MPTP-lesioned marmoset model of Parkinson's disease.
AB  - In Parkinson's disease (PD), degeneration of the dopaminergic nigrostriatal
      pathway leads to enhanced transmission at NMDA receptors containing NR2B
      subunits. Previous studies have shown that some, but not all, NR2B-containing
      NMDA receptor antagonists alleviate parkinsonian symptoms in animal models of PD.
      Furthermore, enhanced NMDA receptor-mediated transmission underlies the
      generation of L-DOPA-induced dyskinesia (LID). The subunit content of NMDA
      receptors responsible for LID is not clear. Here, we assess the actions of the
      NMDA antagonist CP-101,606 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-lesioned marmoset model of Parkinson's disease. CP-101,606 is selective
      for NMDA receptors containing NR2B subunits, with higher affinity for NR1/NR2B
      complexes compared to ternary NR1/NR2A/NR2B complexes. CP-101,606 had no
      significant effect on parkinsonian symptoms when administered as monotherapy over
      a range of doses (0.1-10 mg/kg). CP-101,606 provided a modest potentiation of the
      anti-parkinsonian actions of L-DOPA (8 mg/kg), although, at doses of 1 and 3
      mg/kg, CP-101,606 exacerbated LID. Results of this study provide further evidence
      of differences in the anti-parkinsonian activity and effects on LID of the NR2B
      subunit selective NMDA receptor antagonists. These distinctions may reflect
      disparities in action on NR1/NR2B as opposed to NR1/NR2A/NR2B receptors.

PMID- 15246847
TI  - Effects of stimulation of the subthalamic area on oscillatory pallidal activity
      in Parkinson's disease.
AB  - The pattern of neuronal discharge within the basal ganglia is disturbed in
      Parkinson's disease (PD). In particular, there is a tendency for neuronal
      elements to synchronise at around 20 Hz in the absence of dopaminergic treatment,
      whereas this activity can be replaced by spontaneous synchronisation at much
      higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21
      (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that
      stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at
      similar frequencies in the globus pallidus interna, the major output structure of
      the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz
      suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the
      subthalamic area at similar high frequencies reverses parkinsonism and forms the
      basis of therapeutic deep brain stimulation in PD. The results point to a
      possible common mechanism by which both dopaminergic treatment associated
      synchronisation of subthalamic activity at very high frequency and
      synchronisation imposed by therapeutic stimulation of the subthalamic area
      inhibit an abnormal and potentially deleterious synchronisation of basal ganglia
      output at around 20 Hz. If this activity is unchecked by synchronisation at
      higher frequency, then pathological 20-Hz oscillations may cascade through the
      basal ganglia, increasing at subsequent levels of processing.

PMID- 15246848
TI  - Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease.
AB  - The safety and tolerability of high dosages of coenzyme Q10 were studied in 17
      patients with Parkinson's disease (PD) in an open label study. The subjects
      received an escalating dosage of coenzyme Q10--1200, 1800, 2400, and 3000 mg/day
      with a stable dosage of vitamin E (alpha-tocopherol) 1200 IU/day. The plasma
      level of coenzyme Q10 was measured at each dosage. Thirteen of the subjects
      achieved the maximal dosage, and adverse events were typically considered to be
      unrelated to coenzyme Q10. The plasma level reached a plateau at the 2400 mg/day
      dosage and did not increase further at the 3000 mg/day dosage. Our data suggest
      that in future studies of coenzyme Q10 in PD, a dosage of 2400 mg/day (with
      vitamin E/alpha-tocopherol 1200 IU/day) is an appropriate highest dosage to be
      studied.

PMID- 15246849
TI  - Lipoic acid pretreatment attenuates ferric chloride-induced seizures in the rat.
AB  - Traumatic brain injury (TBI) is often complicated by the occurrence of seizures,
      which adversely affect clinical outcome. The risk of seizures increases to the
      extent that the injury is associated with sub-arachnoid hemorrhage and hematoma.
      A likely mechanism of seizure development post-TBI is decompartmentalization of
      iron from extravasated hemoglobin (Hb). It is well known that iron can catalyze
      formation of reactive oxygen species (ROS). Based on this proposed mechanism, a
      descriptive model of TBI-induced seizures, using intracortical injection of iron
      salts, was developed by Willmore. We have added modifications to enhance the
      quantifiability of seizure activity and have used the model to examine the
      therapeutic efficacy of lipoic acids (ROS-scavenging antioxidants). Male SD rats
      were pretreated with alpha-lipoic acid (ALA) and dihydrolipoic acid (DHLA) or
      appropriate vehicles. Under anesthesia, unilateral intracortical infusions of
      ferric chloride were performed stereotaxically. EEG was recorded via extradural
      electrodes. EEG was sampled for 10 s of every 60-s interval over a 24-h period
      following injection of ferric chloride. We measured the number of seconds of
      epileptiform discharges or seizure activity in every 10-s EEG sample during the
      24 h. The EEGs of rats pretreated with ALA and DHLA exhibited 55% less seizure
      activity than vehicle-treated ferric chloride-injected animals, suggesting that
      lipoic acids may be of use in preventing or attenuating TBI-induced seizures.

PMID- 15246850
TI  - Human neural stem cells improve sensorimotor deficits in the adult rat brain with
      experimental focal ischemia.
AB  - Ischemic stroke is caused by the interruption of cerebral blood flow that leads
      to brain damage with long-term sensorimotor deficits. Stem cell transplantation
      may recover functional deficit by replacing damaged brain. In this study, we
      attempted to test whether the human neural stem cells (NSCs) can improve the
      outcome in the rat brain with intravenous injection and also determine the
      migration, differentiation and the long-term viabilities of human NSCs in the rat
      brain. Focal cerebral ischemia was induced by intraluminal thread occlusion of
      middle cerebral artery (MCA). One day after surgery, the rats were randomly
      divided into two groups: NSCs-ischemia vs. Ischemia-only. Human NSCs infected
      with retroviral vector encoding beta galactosidase were intravenously injected in
      NSCs-ischemia group (5 x 10(6) cells) and the same amount of saline was injected
      in Ischemia-only group for control. The animals were evaluated for 4 weeks using
      turning in an alley (TIA) test, modified limb placing test (MLPT) and rotarod
      test. Transplanted cells were detected by X gal cytohistochemistry or beta gal
      immunohistochemistry with double labeling of other cell markers. The NSCs
      ischemia group showed better performance on TIA test at 2 weeks, and MLPT and
      rotarod test from 3 weeks after ischemia compared with the Ischemia-only group.
      Human NSCs were detected in the lesion side and labeled with marker for neurons
      or astrocytes. Postischemic hemispheric atrophy was noted but reduced in NSCs
      ischemia group. X gal+ cells were detected in the rat brain as long as 540 days
      after transplantation. Our data suggest intravenously transplanted human NSCs can
      migrate and differentiate in the rat brain with focal ischemia and improve
      functional recovery.

PMID- 15246851
TI  - The upregulation of plasticity-related proteins following TBI is disrupted with
      acute voluntary exercise.
AB  - Following traumatic brain injury (TBI), the brain undergoes a period of metabolic
      and neurochemical alterations that may compromise the reactivity of
      neuroplasticity-related molecular systems to physiological stimulation. In order
      to address the molecular mechanisms underlying plasticity following TBI and the
      effects of physical stimulation in the acute phase of TBI, levels of
      intracellular signaling molecules were assessed following voluntary exercise.
      Lateral fluid percussion injury (FPI) and sham-operated (Sham) rats were housed
      with or without access to a running wheel (RW) from postsurgery day 0 to 6.
      Parietal and occipital cortical tissues were analyzed for brain-derived
      neurotrophic factor (BDNF) using an enzyme-linked immunoabsorbant assay (ELISA).
      In addition, synapsin I, phospho-synapsin I, cyclic-AMP response-element-binding
      protein (CREB), phospho-CREB, calcium-calmodulin-dependent protein kinase II
      (CAMKII), mitogen-activated protein (MAP) kinase I and II (MAPKI and MAPKII), and
      protein kinase C (PKC) were analyzed by western blot. Results from this study
      indicated that FPI alone lead to significant increases in synapsin I, CAMKII, and
      phosphorylated (P) MAPKI (p44) and MAPKII (p42). Exercise in the sham operates
      led to significant cortical increases of CREB and synapsin I. However, in the FPI
      rats, the response to exercise was opposite to that seen in the shams in that
      exercise resulted in significant decreases of CREB, synapsin I, PKC, CAMKII,
      MAPKI, and MAPKII. Indeed, all the observed proteins in the acutely exercised FPI
      rats tended to be lower compared to the FPI sedentary (Sed) rats. These results
      indicate that intracellular signaling proteins are increased during the first
      week following FPI and that premature voluntary exercise may compromise
      plasticity.

PMID- 15246852
TI  - Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic
      aldehyde 3-aminopropanal.
AB  - 3-Aminopropanal (3-AP), a degradation product of polyamines such as spermine,
      spermidine and putrescine, is a lysosomotropic small aldehyde that causes
      apoptosis or necrosis of most cells in culture, apparently by inducing moderate
      or extensive lysosomal rupture, respectively, and secondary mitochondrial
      changes. Here, using the human neuroblastoma SH-SY5Y cell line, we found
      simultaneous occurrence of apoptotic and necrotic cell death when cultures were
      exposed to 3-AP in concentrations that usually are either nontoxic, or only cause
      apoptosis. At 30 mM, but not at 10 mM, the lysosomotropic base and proton
      acceptor NH3 completely blocked the toxic effect of 3-AP, proving that 3-AP is
      lysosomotropic and suggesting that the lysosomal membrane proton pump of
      neuroblastoma cells is highly effective, creating a lower than normal lysosomal
      pH and, thus, extensive intralysosomal accumulation of lysosomotropic drugs. A
      wave of internal oxidative stress, secondary to changes in mitochondrial membrane
      potential, followed and gave rise to further lysosomal rupture. The preincubation
      of cells for 24 h with a chain-breaking free radical-scavenger, alpha-tocopherol,
      before exposure to 3-AP, significantly delayed both the wave of oxidative stress
      and the secondary lysosomal rupture, while it did not interfere with the early 3
      AP-mediated phase of lysosomal break. Obviously, the reported oxidative stress
      and apoptosis/necrosis are consequences of lysosomal rupture with ensuing release
      of lysosomal enzymes resulting in direct/indirect effects on mitochondrial
      permeability, membrane potential, and electron transport. The induced oxidative
      stress seems to act as an amplifying loop causing further lysosomal break that
      can be partially prevented by alpha-tocopherol. Perhaps secondary brain damage
      during a critical post injury period can be prevented by the use of drugs that
      temporarily raise lysosomal pH, inactivate intralysosomal 3-AP, or stabilize
      lysosomal membranes against oxidative stress.

PMID- 15246853
TI  - Quantitative analyses of GFRalpha-1 and GFRalpha-2 mRNAs and tyrosine hydroxylase
      protein in the nigrostriatal system reveal bilateral compensatory changes
      following unilateral 6-OHDA lesions in the rat.
AB  - Copy numbers of mRNAs for GFRalpha-1 and GFRalpha-2, the preferred receptors for
      glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) were
      determined by real-time quantitative RT-PCR (QRT-PCR). Receptor expression was
      assessed in striatum (ST) and substantia nigra (SN) of normal rats and rats
      acutely or progressively lesioned by 6-OHDA injected into the medial forebrain
      bundle or ST, respectively. GFRalpha-1 mRNA was clearly detected in normal ST. In
      normal SN, significantly higher expression of both receptors was observed. At 4
      weeks after acute lesion, GFRalpha-2 mRNA was markedly decreased in SN
      bilaterally, whereas GFRalpha-1 mRNA in SN and ST was not affected. A progressive
      lesion resulted in a progressive decrease of GFRalpha1 mRNA in ST bilaterally. In
      SN, levels of GFRalpha-1 mRNA were not significantly affected by a progressive
      lesion, whereas GFRalpha-2 mRNA was markedly decreased bilaterally. Quantitative
      western blotting standardized against tyrosine hydroxylase (TH) protein from PC12
      cells revealed the expected decrease in TH protein in lesioned SN, but also
      significant increases in TH protein in contralateral, unlesioned SNs at 4 weeks
      after both acute and progressive lesions. These data suggest that previously
      unrecognized compensatory changes in the nigrostriatal system occur in response
      to unilateral dopamine depletion. Since the changes observed in receptor
      expression did not always parallel loss of dopamine neurons, cells in addition to
      the nigral dopamine neurons appear to be affected by a 6-OHDA insult and are
      potential targets for the neurotrophic factors, GDNF and NTN.

PMID- 15246854
TI  - Two types of afferent terminals innervate cochlear inner hair cells in C57BL/6J
      mice.
AB  - Afferent synapses on inner hair cells (IHC) transfer auditory information to the
      central nervous system (CNS). Despite the importance of these synapses for normal
      hearing, their response to cochlear disease and dysfunction is not well
      understood. The C57BL/6J mouse is a model for presbycusis and noise-induced
      hearing loss because of its age-related hearing loss and susceptibility to
      acoustic over-exposure. In this context, we sought to establish normal synaptic
      structure in order to better evaluate synaptic changes due to presbycusis and
      noise exposure. Ultrastructural analysis of IHCs and afferent terminals was
      performed in a normal hearing 3-month-old C57BL/6J mouse at cochlear sites
      corresponding to 8, 16 and 32 kHz using semi-serial sections. A stereologic
      survey of random sections was conducted of IHCs in 11 additional mice. Two
      morphologically distinct groups of afferent terminals were identified at all 3
      frequency locations in 11 out of 12 animals. "Simple" endings demonstrated
      classic features of bouton terminals, whereas "folded" endings were larger in
      size and exhibited a novel morphologic feature that consisted of a fully
      internalized double membrane that partially divided the terminal into two
      compartments. In many cases, the double membrane was continuous with the outer
      terminal membrane as if produced by an invagination. We still must determine the
      generality of these observations with respect to other mouse strains.

PMID- 15246855
TI  - Downregulation of COX-2 and JNK expression after induction of ischemic tolerance
      in the gerbil brain.
AB  - The response of the inducible isoform of the prostaglandin H2 synthase (COX-2)
      and the c-Jun N-terminal kinase (JNK) in post-ischemic neuronal damage was
      assessed in a model of ischemic tolerance in Mongolian Gerbils. After a single 6
      min bilateral carotid occlusion, histological damage was evident in the CA1
      region of hippocampus, correlated with a high expression of JNK and COX-2 mRNA.
      However, in the group of animals with a 2-min ischemia and the tolerance group,
      in which a 2-min bilateral carotid occlusion was followed 3 days later by a 6-min
      ischemia, no hippocampal or cortical damage was detected. Accordingly, the JNK
      and COX-2 mRNA levels remained unaffected. We suggest that the level of JNK and
      COX-2 expression may determine the outcome as either post-ischemic cell death or
      tolerance.

PMID- 15246856
TI  - Coordination of jaw and extrinsic tongue muscle activity during rhythmic jaw
      movements in anesthetized rabbits.
AB  - To clarify the jaw-closer and tongue-retractor muscle activity patterns during
      mastication, electromyographic activity of the styloglossus (SG) as a tongue
      retractor and masseter (Mass) as a jaw-closer muscles as well as jaw-movement
      trajectories were recorded during cortically evoked rhythmic jaw movements
      (CRJMs) in anesthetized rabbits. The SG and Mass muscles were mainly active
      during the jaw-closing (Cl) phase. The SG activity was composed of two bursts in
      one masticatory cycle; one had its peak during the jaw-opening (Op) phase (SG1
      burst) and the other during the Cl phase (SG2 burst). The Mass activity during
      the Cl phase was dominant on the working side (opposite to the stimulating side)
      while the SG1 and SG2 bursts were not different between the sides. When the
      wooden stick was inserted between the molar teeth on the working side during
      CRJMs, the facilitatory effects on the SG1 and SG2 bursts on both sides were
      noted as well as those on the Mass bursts, but the effects on the SG1 burst
      seemed to be weak as compared with those on the Mass and SG2 bursts. The
      difference in the burst timing between the sides was noted only in the SG1 burst.
      When the trigeminal nerves were blocked, the peak and area of the SG and Mass
      burst decreased during CRJMs, and the facilitatory effects of the wooden stick
      application on the muscles were not noted. The results suggest that the jaw and
      tongue muscle activities may be adjusted to chew the food and make the food
      bolus.

PMID- 15246857
TI  - Ingested placenta blocks the effect of morphine on gut transit in Long-Evans
      rats.
AB  - Opioids produce antinociception, and ingested placenta or amniotic fluid modifies
      that antinociception. More specifically, ingested placenta enhances the
      antinociception produced by selective activation of central kappa-opioid or delta
      opioid receptors but attenuates that produced by activation of central mu-opioid
      receptors. Opioids also slow gut transit by acting on central or peripheral mu
      opioid receptors. Therefore, we hypothesized that ingested placenta would reverse
      the slowing of gut transit that is produced by morphine, a preferential mu-opioid
      receptor agonist. Rats were injected with morphine either centrally or
      systemically and fed placenta, after which gastrointestinal transit was
      evaluated. We report here that ingested placenta reversed the slowing of gut
      transit produced by centrally administered morphine but did not affect the
      slowing of gut transit produced by systemically administered morphine. These
      results suggest another likely consequence of placentophagia at parturition in
      mammals--reversal of opioid-mediated, pregnancy-based disruption of
      gastrointestinal function--as well as an important consideration in opioid-based
      treatments for pain in humans--enhancement of desirable effects with attenuation
      of adverse effects.

PMID- 15246858
TI  - Reduced ventromedial hypothalamic neuronal nitric oxide synthase and increased
      sensitivity to NOS inhibition in dietary obese rats: further evidence of a role
      for nitric oxide in the regulation of energy balance.
AB  - Inhibition of hypothalamic nitric oxide (NO) decreases energy intake, and changes
      in hypothalamic NO synthase (NOS) have been observed in genetically obese
      rodents, but it is not known if NO is involved in the development of diet-induced
      obesity (DIO). We therefore measured changes in hypothalamic neuronal NOS (nNOS)
      in DIO and investigated effects of peripheral and central inhibition of NOS in
      this model. Expression of nNOS in relation to changes in nutritional state was
      measured by immunohistochemistry, with radiochemical detection. The effect of
      chronic intraperitoneal (i.p.) administration of the NOS inhibitor N(G)-nitro-L
      arginine methyl ester (L-NAME, 50 mg/kg/day) on energy intake, bodyweight and
      hypothalamic nitric oxide content was assessed in both chow-fed and DIO animals.
      Twenty-four hour energy intake after acute intracerebroventricular (i.c.v.) of L
      NAME was also measured. Diet-induced obese animals had a statistically
      significant 32% reduction in the number of nNOS-immunolabelled cells in the
      ventromedial hypothalamus compared to chow-fed controls. Intraperitoneal
      administration of L-NAME decreased hypothalamic NO content in both chow-fed and
      DIO. Energy intake was reduced by 16% in DIO over 16 days, whereas energy intake
      was only reduced by 11% in chow-fed animals, although both were statistically
      significant. L-NAME significantly reduced body weight gain in DIO but not in chow
      fed rats. L-NAME administered i.c.v. decreased 24 h energy intake to a greater
      extent in DIO rats, by 18%, compared with a 10% reduction in chow-fed rats.
      Ventromedial hypothalamic expression of nNOS is sensitive to changes in
      nutritional state. Despite having reduced nNOS, dietary obese rats were more
      sensitive to the effects of NOS inhibition than lean controls, suggesting a role
      for NO in the development of hyperphagia and obesity in rats fed a palatable
      diet.

PMID- 15246859
TI  - Calcium-independent inhibition of GABA(A) current by caffeine in hippocampal
      slices.
AB  - Although inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptor is
      thought to be affected by intracellular calcium ion concentration ([Ca2+]i),
      origin or route of [Ca2+]i increment has not been well elucidated. Reports on the
      effect of [Ca2+]i elevation on GABA(A)ergic IPSCs per se are also controversial.
      In this study, effects of caffeine and several other [Ca2+]i-mobilizing drugs
      were examined on the IPSCs in acute slices of rat hippocampus. Using the patch
      clamp recording method, spontaneous and evoked currents were recorded from CA3
      neurons. Caffeine strongly inhibited both extra-synaptic and synaptic GABAergic
      IPSCs, regardless of the presence or absence of extracellular Ca2+. This
      inhibition was not relieved by the intracellular application of EGTA or 1,2-bis(2
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA). This inhibition by
      caffeine was not prevented by preequilibration with caffeine. Ca2+ store
      depletion caused by thapsigargin or repetitive stimulation by caffeine could not
      prevent the inhibition. Moreover, ruthenium red and ryanodine could not overcome
      the inhibition. On the contrary, GABA(A)ergic currents were not inhibited by
      stimulation with several Ca2+-mobilizing agonists. Forskolin could not mimic the
      effect of caffeine on the IPSC, and caffeine inhibited the IPSC in the presence
      of adenosine. These results suggest that intracellular Ca2+ mobilization through
      ryanodine-sensitive store stimulation does not significantly affect GABAergic
      IPSCs, and most of the inhibitory effect of caffeine is independent of [Ca2+]i
      elevation under the present experimental conditions.

PMID- 15246860
TI  - Noradrenergic regulation of prolactin secretion at the level of the
      paraventricular nucleus of the hypothalamus: functional significance of the alpha
      1b and beta-adrenergic receptor subtypes.
AB  - Previous research has demonstrated that in the Siberian hamster, both photoperiod
      and estrous cyclicity alter the profile of noradrenergic activity with the
      paraventricular nucleus of the hypothalamus (PVN), and that noradrenergic
      activity is correlated with changes in circulating levels of prolactin. Work from
      our laboratory has demonstrated an inhibitory role for norepinephrine (NE) acting
      at the alpha-2 receptor subtype within the PVN on serum prolactin levels;
      however, the functional significance of other adrenergic receptor subtypes on
      this system is unknown. The purpose of this study was to investigate the
      functional significance of the alpha-1b and beta-adrenergic receptor subtypes at
      the level of the PVN on circulating levels of prolactin. These experiments were
      performed in male Siberian hamsters using reverse microdialysis coupled with
      serial blood sampling. In Experiment 1, infusion of l-phenylephrine hydrochloride
      (alpha-1b agonist) initiated a dose-dependent increase in circulating prolactin,
      whereas infusion of chloroethylclonidine (alpha-1b antagonist) induced a
      significant dose-dependent decline in prolactin. In Experiment 2,
      intraparaventricular administration of propranolol (beta antagonist) initiated a
      significant increase in prolactin levels in a dose-dependent manner, whereas
      isoproterenol (beta agonist) induced a dose-dependent decline in prolactin. The
      results of this study indicate that both the alpha-1b and beta-adrenergic
      receptor subtypes have a significant role in regulating circulating levels of
      prolactin at the level of the PVN in the Siberian hamster.

PMID- 15246862
TI  - Music improves dopaminergic neurotransmission: demonstration based on the effect
      of music on blood pressure regulation.
AB  - The mechanism by which music modifies brain function is not clear. Clinical
      findings indicate that music reduces blood pressure in various patients. We
      investigated the effect of music on blood pressure in spontaneously hypertensive
      rats (SHR). Previous studies indicated that calcium increases brain dopamine (DA)
      synthesis through a calmodulin (CaM)-dependent system. Increased DA levels reduce
      blood pressure in SHR. In this study, we examined the effects of music on this
      pathway. Systolic blood pressure in SHR was reduced by exposure to Mozart's music
      (K.205), and the effect vanished when this pathway was inhibited. Exposure to
      music also significantly increased serum calcium levels and neostriatal DA
      levels. These results suggest that music leads to increased calcium/CaM-dependent
      DA synthesis in the brain, thus causing a reduction in blood pressure. Music
      might regulate and/or affect various brain functions through dopaminergic
      neurotransmission, and might therefore be effective for rectification of symptoms
      in various diseases that involve DA dysfunction.

PMID- 15246861
TI  - Intraspecific variation in estrogen receptor alpha and the expression of male
      sociosexual behavior in two populations of prairie voles.
AB  - Estrogen (E) regulates a variety of male sociosexual behaviors. We hypothesize
      that there is a relationship between the distribution of estrogen receptor alpha
      (ERalpha) and the degree of male social behavior. To test this hypothesis,
      ERalpha immunoreactivity (IR) was compared in prairie voles (Microtus
      ochrogaster) from Illinois (IL), which are highly social, and Kansas (KN), which
      are less social. The expression of androgen receptors (AR) in males also was
      compared between populations. The expression of ERalpha and AR were compared in
      brains from KN and IL males and females using immunocytochemistry (ICC). There
      were significant intrapopulational differences, with males expressing less
      ERalpha-IR than females in the medial preoptic area, ventromedial nucleus,
      ventrolateral portion of the hypothalamus, and bed nucleus of the stria
      terminalis (BST). IL males also displayed less ERalpha-IR in the medial amygdala
      (MeA) than IL females. While IL males expressed significantly less ERalpha-IR in
      the BST and MeA than KN males, there was no difference in AR-IR. Differences in
      the pattern of ERalpha-IR between KN and IL males were behaviorally relevant, as
      low levels of testosterone (T) were more effective in restoring sexual activity
      in castrated KN males than IL males. The lack of difference in AR combined with
      lower expression of ERalpha-IR in IL males suggests that behavioral differences
      in response to T are associated with aromatization of T to E and that reduced
      sensitivity to E may facilitate prosocial behavior in males.

PMID- 15246863
TI  - Effects of tramadol on alpha2-adrenergic receptors in the rat brain.
AB  - In recent years, it has been postulated that tramadol, used mainly for the
      treatment of moderate to severe pain, might display a potential as an
      antidepressant drug. The present study investigated the effects of acute and
      repeated tramadol administration on the binding of [3H]RX 821002, a selective
      alpha2-adrenergic receptor ligand, in the rat brain. Male Wistar rats were used.
      Tramadol (20 mg/kg, i.p.) administered acutely (single dose), at 24 h after
      dosing, induced a significant decrease in the alpha2-adrenergic receptors in all
      brain regions studied. The most pronounced effects were observed in all
      subregions of the olfactory system, nucleus accumbens and septum, thalamus,
      hypothalamus, amygdala, and cerebral cortex. Repeated treatment with tramadol (20
      mg/kg, i.p., once daily for 21 days) also induced statistically significant
      downregulation of [3H]RX 821002 binding sites in the rat brain. However, the
      effect--although statistically significant--was less pronounced than in the group
      treated acutely with the drug. Since drugs such as mianserin and mirtazapine are
      potent antagonists of central alpha2-adrenergic receptors and are effective
      antidepressants, it is tempting to suggest that, in addition to other alterations
      induced by tramadol, downregulation of these receptors may represent a potential
      antidepressant efficacy. On the other hand, one should be careful to avoid the
      treatment of chronic pain with tramadol in patients already receiving
      antidepressant drugs. Tramadol-induced downregulation of alpha2-adrenergic
      receptors--when combined with ongoing antidepressant therapy with drugs, which
      themselves inhibit serotonin reuptake or are antagonists of alpha2-adrenergic
      receptors--might cause threatening complications.

PMID- 15246864
TI  - Aspartoacylase deficiency does not affect N-acetylaspartylglutamate level or
      glutamate carboxypeptidase II activity in the knockout mouse brain.
AB  - Aspartoacylase (ASPA)-deficient patients [Canavan disease (CD)] reportedly have
      increased urinary excretion of N-acetylaspartylglutamate (NAAG), a neuropeptide
      abundant in the brain. Whether elevated excretion of urinary NAAG is due to ASPA
      deficiency, resulting in an abnormal level of brain NAAG, is examined using ASPA
      deficient mouse brain. The level of NAAG in the knockout mouse brain was similar
      to that in the wild type. The NAAG hydrolyzing enzyme, glutamate carboxypeptidase
      II (GCP II), activity was normal in the knockout mouse brain. These data suggest
      that ASPA deficiency does not affect the NAAG or GCP II level in the knockout
      mouse brain, if documented also in patients with CD.

PMID- 15246865
TI  - Enhanced expression of erythropoietin in the central nervous system of SOD1(G93A)
      transgenic mice.
AB  - In the present study, we investigated the changes of erythropoietin (Epo)
      expression in the central nervous system (CNS) of SOD1(G93A) transgenic mice as
      an in vivo model of amyotrophic lateral sclerosis (ALS). In wild-type SOD1
      (wtSOD1) transgenic mice, little immunoreactivity was found in all cortical
      regions. In the cerebral cortex of symptomatic SOD1(G93A) transgenic mice, there
      was a significant increase in Epo immunoreactivity. In the hippocampal formation,
      layer-specific alterations in the staining intensity were observed in the CA1-3
      areas and dentate gyrus. Epo immunoreactivity was significantly increased in the
      midbrain, cerebellar cortex and brainstem of SOD1(G93A) transgenic mice. On the
      contrary, Epo immunoreactivity was moderately stained in the spinal cord and was
      not different between wtSOD1 and SOD1(G93A) transgenic mice at the age of 8
      weeks, 13 weeks and 18 weeks. In the staining of Epo receptor (EpoR), the
      changing pattern was similar with that of Epo in the spinal cord and hippocampal
      formation in wtSOD1 and SOD1(G93A) transgenic mice. Although further studies of
      functional features of Epo in ALS are needed, the first demonstration of
      increased immunoreactivity for Epo in the CNS of SOD1(G93A) transgenic mice may
      provide initial insights into the development of interventional strategies to
      alleviate motor neuron degeneration in human ALS.

PMID- 15246866
TI  - Characterization of hydroxyl radical generation in the striatum of free-moving
      rats due to carbon monoxide poisoning, as determined by in vivo microdialysis.
AB  - Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min
      resulted in stimulation of hydroxyl radical (*OH) generation (estimated by
      measuring 2,3-dihydroxybenzoic acid (2,3-DHBA) production from salicylic acid) in
      the striatum of free-moving rats, as determined by means of brain microdialysis.
      Pretreatment with a voltage-dependent Na+ channel blocker, tetrodotoxin (TTX),
      lowered the basal level of 2,3-DHBA and strongly suppressed the increase in 2,3
      DHBA induced by CO poisoning. CO poisoning significantly, though only slightly,
      increased extracellular glutamate in the striatum, and glutamate (Glu) receptor
      antagonists, such as MK-801 (dizocilpine) and NBQX, failed to suppress the CO
      induced increase in 2,3-DHBA. These findings suggest that CO poisoning may induce
      Na+ influx via the voltage-dependent Na+ channels, resulting in stimulation of
      *OH generation in rat striatum. This effect may be independent of Glu receptor
      activation by increased extracellular Glu.

PMID- 15246867
TI  - IL-4 modulates transcriptional control of the mannose receptor in mouse FSDC
      dendritic cells.
AB  - The mannose receptor is a 175 kDa protein found on the surface of macrophages and
      dendritic cells whose functions include clearance of extracellular hydrolases,
      internalization of pathogens, and antigen capture. Receptor expression is closely
      linked to the functional state of these cells and is regulated by cytokines.
      Previous work has shown that treatment of macrophages and dendritic cells with
      interleukin-4 leads to increased mannose receptor expression. We have examined
      the mechanism of this IL-4-mediated up-regulation in the murine dendritic cell
      line FSDC. IL-4 increased mannose receptor activity, protein, and mRNA. The
      mannose receptor promoter was functional in FSDCs using transient transfection
      assays, and IL-4 treatment increased promoter activity 2.6-fold. The responsive
      region was localized to the proximal 228 bp. Electrophoretic mobility shift
      assays detected an IL-4-inducible protein that bound to the mannose receptor
      promoter at a site spanning the region between -147 and -108 bp. The sequence
      TTAC(N)4CACC (-135 and -124 bp) is similar to the IL-4 response region in the Fc
      receptor II. Mutation of the flanking TT and CC in this motif blocked IL-4
      responsiveness and binding of the IL-4-induced mannose receptor binding protein.
      This protein does not appear to be STAT6 since neither an anti-STAT6 antibody nor
      a STAT6 consensus oligonucleotide altered factor binding.

PMID- 15246868
TI  - Properties of proteins in cancer procoagulant preparations that are detected by
      anti-tissue factor antibodies.
AB  - Cancer procoagulant (CP) and tissue factor (TF; only in complex with Factor VIIa
      (FVIIa)) can activate FX to FXa. Controversy still exists whether or not CP is an
      entity different from TF, or whether CP activity is due to contamination of CP
      preparations with TF/FVIIa complex. We therefore looked for proteins in CP
      preparations that were detected by anti-TF antibodies and then sequenced these
      proteins. One- and two-dimensional gels of CP and TF were used to identify
      proteins immunoreactive to monoclonal anti-CP and anti-TF antibodies (Mabs).
      Those proteins in the CP preparation recognized by anti-TF antibodies were
      sequenced. Angiotensinogen precursor, alpha-1-antitrypsin precursor, and vitamin
      D-binding protein were identified along with one so far unidentified sequence;
      however, no TF-sequences were identified. Also, no proteins with the correct
      molecular weight for TF were identified using anti-TF antibodies. It seems
      possible that CP preparations contain proteins that have some epitopes similar to
      the epitopes recognized in TF by anti-TF Mab. However, these proteins do neither
      have the molecular weight nor the amino acid sequence of TF.

PMID- 15246869
TI  - Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and
      in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2
      aminobutyric acid.
AB  - The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose
      dependent insulinotropic polypeptide (GIP), are currently being considered as
      prospective drug candidates for treatment of type 2 diabetes. Interest in these
      gut hormones was initially spurred by their potent insulinotropic activities, but
      a number of other antihyperglycaemic actions are now established. One of the
      foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid
      degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV
      (DPP IV). Here, we compare the DPP IV resistance and biological properties of
      Abu8/Abu2 (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered
      to impart DPP IV resistance. Whereas (Abu8)GLP-1 was completely stable to human
      plasma (half-life >12 h), GLP-1, GIP, and (Abu2)GIP were rapidly degraded (half
      lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly
      (Abu8)GLP-1 elicited significant adenylate cyclase and insulinotropic activity,
      while (Abu2)GIP was less effective. Similarly, in obese diabetic (ob/ob) mice,
      GIP, GLP-1, and (Abu8)GLP-1 displayed substantial glucose-lowering and insulin
      releasing activities, whereas (Abu2)GIP was only weakly active. These studies
      illustrate divergent effects of penultimate amino acid Ala8/Ala2 substitution
      with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu8)GLP
      1 represents a potential candidate for future therapeutic development.

PMID- 15246870
TI  - A novel UV laser-induced visible blue radiation from protein crystals and
      aggregates: scattering artifacts or fluorescence transitions of peptide electrons
      delocalized through hydrogen bonding?
AB  - Proteins lacking prosthetic groups and/or cofactors are known to undergo
      electronic excitation transitions only upon exposure to UV-C (< 280 nm) and UV-B
      (280-320 nm), but not UV-A (320-400 nm) photons. Here, we report the discovery of
      a novel excitation that peaks at approximately 340 nm and yields visible violet
      blue radiation with apparent band maxima at approximately 425, 445, 470, and 500
      nm. All proteins and large polypeptides examined in solid form, and in solutions,
      display this quenchable and photobleachable radiation which can be established
      not owing to aromatic sidechains. As a note of caution, we wish to state that we
      have not been able to completely eliminate the possibility that the radiation may
      be an artifact owing to second order effects such as, e.g., Raman scattering of
      Raman-scattered photons; however, we assert that all our experiments indicate
      that the radiation actually owes to some form of fluorescence. We propose that
      peptide electrons that have been delocalized through intramolecular or
      intermolecular hydrogen bond formation display these long-wavelength electronic
      transitions. If confirmed by future studies, this preliminary discovery may turn
      out to have important implications for biomolecular spectroscopy, protein
      crystallography, and materials science.

PMID- 15246871
TI  - Changes in quinolinic acid production and its related enzymes following D
      galactosamine and lipopolysaccharide-induced hepatic injury.
AB  - Increases in quinolinic acid (QUIN), a neurotoxic L-tryptophan metabolite, have
      been observed in human serum and cerebrospinal fluid and in animal models of
      severe hepatic injury. The aim of this study was to evaluate the changes in QUIN
      accumulation and its related enzymes after acute hepatic injury induced by D
      galactosamine and endotoxin. Gerbils were given an intraperitoneal injection of
      pyrogen-free saline alone as control, lipopolysaccharide (LPS) alone (150 ng/kg),
      D-galactosamine alone (500 mg/kg) or a combination of D-galactosamine with LPS.
      Concentrations of QUIN, its related metabolites, and related enzyme activities
      were determined. D-Galactosamine treatment significantly decreased activities of
      hepatic aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) resulting in
      increased QUIN concentrations in serum and tissues. The magnitude of QUIN
      responses was markedly increased by endotoxin due to the increased availability
      of L-kynurenine, a rate-limiting substrate for QUIN synthesis. Further,
      infiltration of monocytes/macrophages, which is a possible major source of QUIN
      production in the liver, was shown by immunohistochemistry after hepatic injury
      induced by D-galactosamine and endotoxin. Increased serum QUIN concentrations are
      probably due to the increased substrate availability and the decreased activity
      of aminocarboxymuconate-semialdehyde decarboxylase in the liver, accompanying the
      increased monocyte/macrophage infiltration into the liver after hepatic injury.

PMID- 15246872
TI  - Ubc9-induced inhibition of diadenosine triphosphate hydrolase activity of the
      putative tumor suppressor protein Fhit.
AB  - Fhit protein is the product of the putative tumor suppressor fragile histidine
      triad (FHIT) gene. The way by which Fhit exerts its antitumor activity remains
      largely unknown, although the Fhit-Ap3A complex is believed to be the native
      signaling form of Fhit. Here, we have shown that Fhit protein interacts with
      hUbc9, a recombinant human SUMO-1 conjugating enzyme, in an
      adenosine(5')triphospho(5')nucleoside (Ap3N)-dependent manner. Our experiments
      showed that the dinucleoside polyphosphate hydrolase activity of Fhit is
      suppressed by interacting with hUbc9 protein. In the presence of equimolar hUbc9
      the Vmax and Km activity of Fhit was decreased by 35%. Analysis of Fhit kinetics
      in the presence of different fixed concentrations of Ubc9 showed that Ubc9 is an
      uncompetitive inhibitor. Including SUMO-1 protein in the assay neither affected
      the Fhit activity nor modified the effect of Ubc9 on Fhit kinetics. Our data
      suggest that hUbc9-induced inhibition of Fhit may result in an elongation of the
      Fhit-Ap3A signaling complex lifetime leading to alteration of its antitumor
      activity.

PMID- 15246873
TI  - Interaction of Doppel with the full-length laminin receptor precursor protein.
AB  - Doppel (Dpl) is a homolog of normal cellular prion protein (PrPc) with unknown
      functions. Ectopic expression of Dpl in the central nervous system (CNS) causes
      neurotoxicity and this effect is rescued by the expression of PrPc. However, the
      molecular basis for the protective effect of PrPc remains unclear. Using a yeast
      two-hybrid system, we showed that Dpl binds the full-length 37-kDa laminin
      receptor precursor protein (LRP), one of the receptors of PrPc. The interaction
      was also validated by immunoprecipitation and immunoblotting using transfected
      cell lines and in vivo derived tissues. Further mapping experiments showed that
      although the middle fragment containing residues 100-220 of LRP was able to
      interact with Dpl, deletion of the N-terminal domain of the full-length LRP
      abolished its interaction with Dpl. These results suggest that while both PrPc
      and Dpl interact with LRP, the domains that are involved in the binding are not
      the same. Our results may have implications for the molecular mechanisms of Dpl
      PrPc antagonism and physiological roles of Dpl.

PMID- 15246874
TI  - Molecular cloning and biological characterization of novel antimicrobial
      peptides, pilosulin 3 and pilosulin 4, from a species of the Australian ant genus
      Myrmecia.
AB  - Venom of an Australian ant species of the Myrmecia pilosula species complex (mss.
      name Myrmecia banksi Taylor) contains two major allergenic peptides, pilosulin 1
      and pilosulin 2. To obtain novel cDNA clones that encode the pilosulin-related
      bioactive peptides, mRNA of another Myrmecia species was subjected to RT-PCR in
      which the forward primer corresponds to a nucleotide sequence in the leader
      sequences of pilosulin 1 and pilosulin 2. As a result, we isolated cDNA clones
      encoding the novel antimicrobial peptides pilosulin 3 and pilosulin 4. The
      nucleotide and the amino acid sequences of all four pilosulins have high homology
      except for the mature peptide coding regions. Synthetic pilosulin 3 and pilosulin
      4 peptides displayed antimicrobial activity with histamine-releasing and low
      hemolytic activities.

PMID- 15246876
TI  - Functional independence of a peptide with the sequence of human apolipoprotein A
      I central region.
AB  - Previous results [J. Biol. Chem. 276 (2001) 16978] indicated that an
      apolipoprotein A-I (apoAI) central region swings away from lipid contact in
      discoidal high density lipoproteins (HDL), but it is able to penetrate into the
      bilayer of lipid vesicles. In this work, we have studied the interaction with
      lipid membranes of a synthetic peptide with the sequence of apoAI region between
      residues 77 and 120 (AI 77-120). Like apoAI, AI 77-120 binds to phospholipid
      vesicles and shows selectivity for cholesterol-containing membranes. Moreover, AI
      77-120 promotes cholesterol desorption from membranes in a similar fashion as
      apoAI and can stimulate cholesterol efflux from Chinese hamster ovary cells. AI
      77-120 has a considerable alpha-helical content in water solution, and its
      secondary structure is not largely modified after binding to membranes. Both apoA
      I and AI 77-120 are oligomeric in the lipid-bound state, suggesting that
      dimerization of the central domain could be required for the membrane binding
      activity of apoA-I in HDL.

PMID- 15246875
TI  - Involvement of reactive oxygen species-independent mitochondrial pathway in
      gossypol-induced apoptosis.
AB  - Gossypol is a component present in cottonseeds and has been demonstrated to be an
      effective contraceptive drug in preventing spermatogenesis in mammalian species.
      In the present, we reported that gossypol could induce apoptosis in human
      promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation,
      poly(ADP) ribose polymerase (PARP) cleavage. The efficacious induction of
      apoptosis was observed at 50 microM for 6 h. Further molecular analysis showed
      that gossypol induced the truncation of Bid protein, the loss of mitochondrial
      membrane potential (DeltaPsi m), cytochrome c release from mitochondria into
      cytosol, and activation of caspase-3, -8, and -9. However, gossypol did not
      increase the level of reactive oxygen species (ROS), and antioxidants including N
      acetyl cysteine (NAC) and catalase could not block gossypol-induced apoptosis in
      the HL-60 cells. These data suggest that gossypol induces apoptosis in HL-60
      cells through ROS-independent mitochondrial dysfunction pathway.

PMID- 15246877
TI  - S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates
      apoptosis signal-regulating kinase 1.
AB  - In the present study, we have investigated S-nitrosation of reactive thioredoxin
      (Trx) thiol groups in nitric oxide/superoxide system. We have found that Trx
      thiol groups are the targets for S-nitrosation by N2O3-like species generated in
      the system containing xanthine/xanthine oxidase (superoxide producing system) and
      DEA/NO-the *NO donating compound, however, they have shown low sensitivity to the
      *NO derived from DEA/NO. N2O3-dependent S-nitrosation of Trx at approximately 2
      fold of NO excess compared to the superoxide amount resulted in dissociation and
      activation of apoptosis signal regulating kinase 1 (ASK1). However, approximately
      4-fold of NO excess compared to a superoxide production preserved the level of
      dissociated ASK1 but decreased its activity due to the enzyme S-nitrosation.

PMID- 15246878
TI  - Experimental evidence that flavonoid metal complexes may act as mimics of
      superoxide dismutase.
AB  - Radical scavenging activities of flavonoids rutin, taxifolin, (-)-epicatechin,
      luteolin, and their complexes with transition metal (Fe2+, Fe3+, and Cu2+)
      towards superoxide were determined using illumination of riboflavin as source and
      NBT as detector of O*2-. The scavenger potencies of flavonoid metal complexes
      were significantly higher than those of the parent flavonoids. To elucidate the
      mechanism of this phenomenon, the rates of superoxide-dependent oxidation of
      flavonoids and their metal complexes in photochemical system with riboflavin were
      examined. It was found for the first time that flavonoids bound to metal ions
      were much less subjected to oxidation compared with those of free compounds. The
      findings directly demonstrate superoxide scavenging activity of metal ions in
      complexes with flavonoids and support earlier suggestions that flavonoid metal
      complexes may exhibit superoxide dismuting activity.

PMID- 15246879
TI  - Arm work interferes with normal ventilation.
AB  - Arm work, by limiting movement of the chest wall and use of the respiratory
      muscles, may alter breathing pattern and gas exchange sufficiently to interfere
      with the ability to perform certain tasks. To determine the effects of arm work
      on breathing pattern during a well-controlled work task, depth of breathing,
      breathing frequency and end-expiratory lung volume (EELV) were measured at rest
      and during cycling exercise using an arm and a leg ergometer. Six subjects
      performed arm work at light, moderate and heavy intensities (30%, 60% and 90% of
      maximum arm work capacity respectively) and leg work at three intensities where
      ventilation was matched for that achieved during the arm work. This matching was
      necessary since the level of ventilation affects the breathing pattern. Subjects
      breathed on a mouthpiece and tubing that led to automated equipment for the
      measurement of respiratory variables. Ventilation during arm work was
      accomplished with a lower depth of breathing, a higher breathing frequency and a
      decreased EELV compared to leg work. Arm work places increased demands on the
      ventilatory system, including the muscles of respiration that are also recruited
      for task performance. The competition for using these muscles for breathing as
      opposed to a particular work task may result in a compromise in breathing
      capacity that ultimately may limit the ability to perform tasks requiring
      sustained heavy use of the arms. These increased demands on the upper body
      muscles must be considered when evaluating the ability of individuals to perform
      tasks that involve heavy arm work.

PMID- 15246880
TI  - Musculoskeletal symptoms among commercial fishers in North Carolina.
AB  - Musculoskeletal symptoms were reported by 215 fishermen followed at 6-month
      intervals over 18 months. Exposure information was collected through field
      observation and in-depth ethnographic interviews allowing potential ergonomic
      stressors to be identified and catalogued by task and stage of work. Symptoms
      causing work interference in the last 12 months were reported by 38.5% of the
      cohort at baseline. Low back symptoms were the most common cause of work
      impairment (17.7%), followed equally by pain in the hands or wrists and shoulders
      (7%). Symptoms in any body region were more likely to have been reported among
      individuals who did not fish full-time and those who worked other jobs part or
      all year had significantly lower symptom prevalence; both likely reflect a
      healthy worker effect. A number of ergonomic stressors were identified in all
      stages of fishing with exposure variability dictated by some unpredictable
      factors such as weather; but also by type of boat, gear, crew size, and level of
      experience. Reducing ergonomic exposures associated with work among these
      traditional workers is important, regardless of whether they directly cause or
      contribute to their musculoskeletal symptoms, or aggravate existing pathology.

PMID- 15246881
TI  - A participatory ergonomics intervention to reduce risk factors for low-back
      disorders in concrete laborers.
AB  - Construction laborers rank high among occupational groups with work-related
      musculoskeletal injuries involving time way from work. The goals of this project
      were to: (1) introduce an ergonomic innovation to decrease the risk of low-back
      disorder (LBD) group membership, (2) quantitatively assess exposure, and (3)
      apply a participatory intervention approach in construction. Laborers manually
      moving a hose delivering concrete to a placement site were evaluated. The
      hypothesis tested was that skid plates would prevent hose joints from catching on
      rebar matting, and the hose would slide more easily. This would decrease the need
      for repetitive bending and use of excessive force. Four laborers were evaluated
      wearing the Lumbar Motion Monitor (LMM), a tri-axial electrogoniometer that
      records position, velocity and acceleration. Workers were measured during three
      comparable concrete pours. Worker perceptions of the innovation utility and
      exertion were surveyed. During initial use of skid plates, flexion increased
      significantly (p < 0.001) while velocity, acceleration and moments did not
      change. After implementing a worker modification, low back velocity, acceleration
      and moments were significantly reduced (p < 0.05). Reductions in these factors
      have been associated with decreased risk of belonging to an occupational group
      with LBDs. Use of secured skid plates during horizontal concrete hose movement
      may in part decrease the risk of LBD group membership among concrete laborers.
      Crew participation resulted in skid plates being a more effective intervention.
      The LMM is a promising tool for quantitative assessment in construction.

PMID- 15246882
TI  - Representing older and disabled people in virtual user trials: data collection
      methods.
AB  - A database was developed to support the creation of a computer-based tool which
      will support design teams in evaluating the usability of a design during early
      prototyping and indicate which individuals are effectively excluded or designed
      out. Methods are described for the collection of multivariate data on 100 real
      individuals covering a range of physical characteristics and capabilities. These
      data were tested to ensure a breadth of representation of individuals
      (particularly older and disabled people) in terms of anthropometry, joint
      constraints, postural capabilities and task behaviours. The concept of the design
      tool itself is explored by conducting virtual user trials in the computer-aided
      design environment. The novel approach of the research encourages empathy with
      individual users and allows generic abilities, such as bending, reaching and
      lifting to be assessed.

PMID- 15246883
TI  - Identifying factors of comfort in using hand tools.
AB  - To design comfortable hand tools, knowledge about comfort/discomfort in using
      hand tools is required. We investigated which factors determine
      comfort/discomfort in using hand tools according to users. Therefore, descriptors
      of comfort/discomfort in using hand tools were collected from literature and
      interviews. After that, the relatedness of a selection of the descriptors to
      comfort in using hand tools was investigated. Six comfort factors could be
      distinguished (functionality, posture and muscles, irritation and pain of hand
      and fingers, irritation of hand surface, handle characteristics, aesthetics).
      These six factors can be classified into three meaningful groups: functionality,
      physical interaction and appearance. The main conclusions were that (1) the same
      descriptors were related to comfort and discomfort in using hand tools, (2)
      descriptors of functionality are most related to comfort in using hand tools
      followed by descriptors of physical interaction and (3) descriptors of appearance
      become secondary in comfort in using hand tools.

PMID- 15246884
TI  - Representation of a human head with bi-cubic B-splines technique based on the
      laser scanning technique in 3D surface anthropometry.
AB  - Three-dimensional (3D) anthropometry based on the laser scanning technique not
      only provides one-dimensional measurements calculated in accordance with the
      landmarks which are pre-located on the human body surface manually, but also the
      3D shape information between the landmarks. This new technique used in recent
      ergonomic research has brought new challenges to resolving the application
      problem that was generally avoided by anthropometric experts in their researches.
      The current research problem is concentrating on how to shift and develop one
      dimensional measurements (1D landmarks) into three-dimensional measurements (3D
      land-surfaces). The main purpose of this paper is to test whether the function of
      B-splines can be used to fit 3D scanned human heads, and to for further study to
      develop a computer aided ergonomic design tool (CAED). The result shows that B
      splines surfaces can effectively reconstruct 3D human heads based on the laser
      scanning technique.

PMID- 15246885
TI  - Objective measurement of the start-motion quality of a forklift truck.
AB  - An objective index is developed for the estimation of ride quality during a
      forklift truck start. After consultation with test drivers, start-motion quality
      is defined and three governing parameters selected: engagement shock in the
      driving direction, vertical vibration, and pitch vibration. Subjective evaluation
      of the starting motion and objective measurements of vehicle vibration were
      performed on five forklift trucks with various load capacities. The vibration
      measured at the driver's seat was changed into a perceptual amount by using the
      frequency weighting curves and the fourth power dose method suggested in ISO 2631
      1 (Mechanical Vibration and Shock-evaluation of Human Exposure to Whole-body
      Vibration--Part 1: General Requirements. International Organization for
      Standardization). Regression between the perceptual vibrations, expressed as a
      vibration dose value, and the subjective rating scores yielded an index equation
      in the form of Steven's psychophysical power law: psi = 1.912phi(-0.601), where
      psi is the sensation magnitude of start-motion quality and phi is the stimulus
      magnitude of the vibration dose value.

PMID- 15246886
TI  - Development of risk filter and risk assessment worksheets for HSE guidance-
      'Upper Limb Disorders in the Workplace' 2002.
AB  - Upper limb disorders (ULDs) in the workplace represent a significant cause of ill
      health in Great Britain. As part of the Health and Safety Commission's strategy
      for the prevention of musculoskeletal disorders (MSDs), the well known guidance
      document on ULDs--"Work-related Upper Limb Disorders: a Guide to Prevention"
      (HSG60), (HMSO, London.), has been extensively revised. This revision (Upper limb
      disorders in the workplace. HSG60 (rev), HSE Books, Sudbury.) includes the
      development of new risk assessment tools that can be used by employers to
      identify ULD risk factors in work activities and more importantly to take action
      to reduce or eliminate ULD risks. The risk assessment tools form part of a seven
      stage management approach that underpins the new guidance. This paper outlines
      the development of the risk assessment tools contained in the revised guidance.

PMID- 15246887
TI  - One set of pliers for more tasks in installation work: the effects on
      (dis)comfort and productivity.
AB  - In installation work, the physical workload is high. Awkward postures, heavy
      lifting and repetitive movements are often seen. To improve aspects of the work
      situation, frequently used pliers were redesigned to make them suitable for more
      cutting tasks. In this study these multitask pliers are evaluated in comparison
      to the originally used pliers in a field study and a laboratory study. For the
      field study 26 subjects participated divided into two groups according to their
      type of work. Ten subjects participated in the laboratory study. The multitask
      plier appeared to result in more comfort during working, more relaxed working and
      more satisfaction. No differences in productivity were found. In conclusion, the
      multitask pliers can replace the originally used pliers and are suitable for more
      tasks than the original pliers. The installation workers have to carry less
      pliers by using the multitask pliers.

PMID- 15246888
TI  - Ergonomic intervention in carpet mending operation.
AB  - Carpet mending operations are performed in traditional workshops in a squatting
      position. Seventy-two menders were questioned regarding musculoskeletal disorders
      (MSDs). Among the menders, knees, back and shoulders problems were more prevalent
      compared to other body regions. Based on the problems found, a new workstation
      was developed and eight menders were asked to work in the new workstation. They
      were observed and evaluated with the RULA technique and their opinion on the
      improvement was asked working on four frequently seen tasks. The new workstation
      improved working posture noticeably. In 57% of the cases, the new workstation was
      evaluated good or very good and the comfort was increased.

PMID- 15246889
TI  - Effects of rosiglitazone on endothelial function in men with coronary artery
      disease without diabetes mellitus.
AB  - Recent data have shown that peroxisome proliferator-activated receptor-gamma
      agonists may exert protective effects on the vascular endothelium by amelioration
      of insulin resistance and through direct anti-inflammatory effects. In this study
      we assessed the effect of rosiglitazone on biochemical and biophysical indexes of
      endothelial function in male, nondiabetic patients with coronary artery disease.
      Consecutive male subjects (n = 71) with clinically stable, angiographically
      documented coronary artery disease and without diabetes mellitus were
      investigated. Patients were randomized in a double-blind manner to placebo or
      rosiglitazone for a total of 24 weeks. Flow-mediated dilation (FMD) of the
      brachial artery, C-reactive protein, von Willebrand factor, intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 levels, and parameters
      of glucose and lipid metabolism were measured at baseline and after 12 and 24
      weeks of treatment. Rosiglitazone treatment significantly reduced C-reactive
      protein (median 0.56 mg/L [interquartile range 0.33 to 1.02] to 0.33 mg/L
      [interquartile range 0.26 to 0.40], p <0.01), von Willebrand factor (139 +/- 47
      to 132 +/- 44 IU/dl, p = 0.02), insulin resistance index (p = 0.05), and mean low
      density lipoprotein (LDL) density (p <0.001) compared with placebo. However, no
      significant differences were seen between the rosiglitazone and placebo groups
      with regard to brachial artery FMD, intercellular adhesion molecule-1, or
      vascular cell adhesion molecule-1 levels. Rosiglitazone treatment significantly
      increased LDL (2.62 +/- 0.72 to 2.95 +/- 0.84 mmol/L, p = 0.03) and triglyceride
      (1.23 +/- 0.63 to 1.56 +/- 0.98 mmol/L, p = 0.04) levels. Thus, rosiglitazone
      reduced markers of inflammation and endothelial activation, but this did not
      translate into an improvement in FMD. Increased LDL and triglyceride levels may
      have played a role.

PMID- 15246890
TI  - Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in
      patients with hypercholesterolemia.
AB  - Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been associated
      with attenuated endothelium-dependent vasodilation in hypercholesterolemic
      patients. However, whether lowering of plasma cholesterol concentration by
      hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) can reduce plasma
      ADMA levels is still not clear. This study was a multicenter, randomized, double
      blind, placebo-controlled design including 46 patients with elevated low-density
      lipoprotein cholesterol levels. Patients were randomized into 2 groups:
      rosuvastatin 10 mg/day and placebo for 6 weeks. Plasma levels of ADMA, 8
      isoprostane (as a marker of oxidative stress), homocysteine, and high-sensitivity
      C-reactive protein were measured at baseline and 6 weeks later. Endothelial
      function assessed by flow-mediated vasodilation of the brachial artery was
      performed in 11 patients in the rosuvastatin group and in 12 in the placebo
      group. Baseline characteristics of both groups were similar, and the plasma ADMA
      levels were significantly correlated with 8-isoprostane (r = 0.388, p = 0.008).
      After 6 weeks of treatment, plasma ADMA levels were significantly reduced in the
      rosuvastatin group (from 0.60 +/- 0.19 to 0.49 +/- 0.10 micromol/L, p <0.001).
      Increases in flow-mediated vasodilation were positively correlated with
      reductions in plasma levels of ADMA (p = 0.017) and low-density lipoprotein
      cholesterol (p <0.001). Thus, our findings suggest that treatment with
      rosuvastatin in patients with hypercholesterolemia may lead to a significant
      reduction in plasma ADMA levels, which appear to be related to the improvement in
      endothelial function by rosuvastatin.

PMID- 15246891
TI  - A cardioprotective "polypill"? Independent and additive benefits of lifestyle
      modification.

PMID- 15246892
TI  - Chronic kidney disease is a cardiovascular problem--implications for lipid
      management.

PMID- 15246893
TI  - Heroes.

PMID- 15246894
TI  - Coronary artery bypass: a user's manual.

PMID- 15246895
TI  - Effect of rescue or adjunctive percutaneous coronary intervention of the culprit
      artery after fibrinolytic administration on epicardial flow in nonculprit
      arteries.
AB  - We hypothesized that blood flow in noninfarct arteries would improve after
      percutaneous coronary intervention of the culprit artery in the setting of ST
      elevation myocardial infarction (STEMI). The corrected Thrombolysis In Myocardial
      Infarction (TIMI) frame count was measured in 94 patients (102 arteries) enrolled
      in the INTEGRITI, ENTIRE, and FASTER trials of reduced dose fibrinolytic and
      glycoprotein IIb/IIIa inhibition. The corrected TIMI frame count in nonculprit
      arteries improved by 3.4 +/- 13.4 frames after percutaneous coronary intervention
      but remained significantly slower than flow in normal arteries.

PMID- 15246896
TI  - In-hospital mortality associated with the use of intra-aortic balloon
      counterpulsation.
AB  - We analyzed in-hospital mortality for patients treated with intra-aortic balloon
      counterpulsation from the Benchmark Counterpulsation Outcomes Registry (n =
      25,136). In-hospital mortality was higher in patients who received only medical
      interventions (32.5%) than in those who underwent percutaneous (18.8%) and
      surgical (19.2%) interventions, and was greatest in the first days after hospital
      admission for all 3 intervention types. Therefore, diagnostic evaluation and
      treatment decisions should be made as early as possible, and physicians should be
      aware of associated risk factors in making choices for patients.

PMID- 15246897
TI  - Influence of coronary artery bypass grafting on heart rate turbulence parameters.
AB  - This study evaluated the influence of coronary artery bypass grafting on heart
      rate turbulence (HRT) parameters assessed during 1-year follow-up in patients
      with coronary artery disease. HRT and heart rate variability (HRV) parameters
      significantly worsened 3 months after surgery. After 1 year, HRV parameters and
      turbulence onset returned to preoperative values, whereas turbulence slope
      remained significantly attenuated. Our results show that there is a marked
      attenuation of HRT parameters in the early postoperative period, indicating an
      impairment of baroreflex sensitivity after coronary artery bypass grafting.
      Concomitant depression of HRV parameters points to dysfunction of the autonomic
      nervous system, provoked by perioperative attenuation, as a potential underlying
      cause of impaired baroreflex response.

PMID- 15246898
TI  - Relation of an elevated white blood cell count after percutaneous coronary
      intervention to long-term mortality.
AB  - Increased inflammatory markers are associated with a poor prognosis after
      percutaneous coronary intervention. Leukocytes play a key role in inflammation,
      and an increase in white blood cell (WBC) counts is a nonspecific marker of
      inflammation. In patients undergoing percutaneous coronary intervention, baseline
      WBC counts independently predict long-term mortality. In a pooled cohort of
      patients from the Evaluation of c7E3 for the Prevention of Ischemic Complications
      (EPIC), the Evaluation in PTCA to Improve Long-term Outcome with abciximab
      Glycoprotein IIb/IIIa blockade (EPILOG), and Evaluation of Platelet IIb/IIIa
      inhibitor for STENTing (EPISTENT) trials, postprocedural WBC counts were also
      found to be an independent predictor of long-term mortality.

PMID- 15246899
TI  - Evaluation of a high-dose dexamethasone-eluting stent.
AB  - This study evaluated the safety and efficacy of a dexamethasone-eluting stent
      with a special high dexamethasone-loading dose for treatment of de novo coronary
      lesions in 30 patients. Eight patients had in-stent restenosis (restenosis rate
      31%) at 6-month follow-up, and the in-stent late lumen loss was 0.96 +/- 0.63 mm
      due to an average intimal hyperplasia area obstruction of 32 +/- 21%, indicating
      that high-dose dexamethasone-loaded stents do not significantly reduce neointimal
      proliferation.

PMID- 15246900
TI  - Relation of intimal hyperplasia thickness to stent size in paclitaxel-coated
      stents.
AB  - To determine the relation of intimal hyperplasia thickness to stent size in
      nonpolymeric paclitaxel-coated stents, intravascular ultrasound was performed
      after stent implantation and at 6 months. Similar to bare metal stents, this
      study demonstrated that intimal hyperplasia thickness is independent of stent
      size. There was no deleterious effect of the increased concentration associated
      with using the same stent design in a smaller artery, and these results suggested
      that stent strut density may be a more important concept than drug concentration.

PMID- 15246901
TI  - Comparison of neointimal formation in polymer-free paclitaxel stents versus
      stainless stents (from the ASPECT and ELUTES randomized clinical trials).
AB  - The investigators examined 326 pairs of angiograms from 2 randomized dose-finding
      (0.2 to 3.1 microg paclitaxel/mm(2) of stent surface area) clinical trials of
      polymer-free paclitaxel-eluting stents in de novo lesions (the ASian Paclitaxel
      Eluting stent Clinical Trial [ASPECT] and the European evaLUation of Taxol
      Eluting Stent [ELUTES]). A dose-dependent effect was observed: the largest dose
      of paclitaxel in the 2 trials resulted in a significantly larger proportion of
      lesions at follow-up with <10% diameter stenosis (54% vs 16%, p = 0.00012 in
      ASPECT; 53% vs 21%, p = 0.013 in ELUTES) and with minimal luminal diameter
      located outside the stent compared with control stents (62% vs 20% in ASPECT, 48%
      vs 18% in ELUTES; p <0.05). Also, significantly shorter lesion lengths at 6-month
      follow-up were observed for the doses of 0.7 to 3.1 microg/mm(2) (p <0.03)
      relative to their respective lengths before the procedure compared with control
      stents.

PMID- 15246902
TI  - Lack of usefulness of electron beam computed tomography for detecting coronary
      allograft vasculopathy.
AB  - Fifty-five patients with cardiac allografts were studied by electron beam
      computed tomography for coronary calcification (EBCT CC) and coronary
      arteriography, and from the latter, a coronary index was calculated using the
      size, degree of obstruction, and linear extent of disease of each vessel. There
      was a significant correlation between EBCT CC score and coronary index, but
      receiver-operating characteristic (ROC) analysis demonstrated unsatisfactory
      performance of EBCT CC, and 6 patients had no coronary calcification despite
      having very abnormal coronary indexes. There are pathologic differences between
      coronary allograft vasculopathy and atherosclerosis, and correspondingly, EBCT CC
      has limited usefulness in the cardiac transplant population.

PMID- 15246903
TI  - Effects of atorvastatin (10 mg) on hemostatic and inflammatory parameters in
      hyperlipidemic patients with angiographically proven coronary artery disease.
AB  - Hyperlipidemic patients with coronary heart disease were treated with
      atorvastatin, and its effects on hemostatic and inflammatory parameters were
      assessed. After 3 months of therapy, the plasma levels of plasminogen activator
      inhibitor, prothrombin fragment 1+2, highly sensitive C-reactive protein, von
      Willebrand factor, and fibrinogen were significantly reduced; no significant
      reductions were observed in lipoprotein(a) and tissue plasminogen activator
      antigen levels.

PMID- 15246904
TI  - Hemodynamics of microvascular dysfunction in patients with anterior wall acute
      myocardial infarction.
AB  - This study investigated whether the no-reflow phenomenon in acute myocardial
      infarction (AMI) is associated with an increase in coronary zero flow pressure
      (ZFP), a decrease in coronary arterial conductance, or both phenomena. Coronary
      blood flow velocity and pressure were measured with a Doppler guidewire and a
      pressure wire, respectively, during vasodilation with adenosine triphosphate
      after coronary intervention. The data indicate that the no-reflow phenomenon is
      not necessarily associated with a decrease in coronary arterial conductance but
      with an increase in ZFP. Greater ZFP is associated with more severe microvascular
      dysfunction and worse functional outcomes in patients with AMI.

PMID- 15246905
TI  - Comparison of once daily versus twice daily oral nitrates in stable angina
      pectoris.
AB  - This study aimed to compare patient compliance and treatment effectiveness in
      patients with stable angina pectoris who were treated with oral nitrates
      administered once daily versus twice daily. Using electronic measurement,
      significantly greater adherence to the once daily versus the twice daily nitrate
      regimen in terms of dosing and timing was found. Better effectiveness of the once
      daily formulation was also observed.

PMID- 15246906
TI  - Comparison of presenting features, diagnostic tools, hospital outcomes, and
      quality of care indicators in older (>65 years) to younger, men to women, and
      diabetics to nondiabetics with acute chest pain triaged in the emergency
      department.
AB  - In a total of 4,843 consecutive patients admitted to an emergency department (ED)
      with acute chest pain over a 1-year period, presenting features, diagnostic
      tools, hospital outcomes, and quality-of-care indicators were compared between
      older (n = 1,781) and younger (n = 3,062) patients, men (n = 3,095) and women (n
      = 1,748), and diabetics (n = 856) and nondiabetics (n = 3,987). The results
      showed that after critical pathway implementation, there was an increase in the
      use of evidence-based treatment strategies in the ED and improved outcomes in
      older patients, women, and diabetics, with no more differences in the length of
      ED stay, diagnostic accuracy for myocardial infarction in the ED, door-to
      thrombolysis time, and door-to-balloon time compared with younger patients, men,
      and nondiabetics.

PMID- 15246907
TI  - Accuracy of the triglyceride to high-density lipoprotein cholesterol ratio for
      prediction of the low-density lipoprotein phenotype B.
AB  - This study examined the accuracy of a triglyceride/high-density lipoprotein (HDL)
      cholesterol ratio of 3.8 for the prediction of low-density lipoprotein (LDL)
      phenotype B. The ratio of 3.8 was based on Adult Treatment Panel recommendations
      for normal fasting triglycerides (<150 mg/dl) and HDL cholesterol (>40 mg/dl).
      Fasting blood samples were obtained from 658 patients. LDL phenotype analysis was
      performed by nuclear magnetic resonance spectroscopy. A triglyceride/HDL
      cholesterol ratio of 3.8 divided the distribution of LDL phenotypes with 79% (95%
      confidence interval [CI] 74 to 83) of phenotype B greater than and 81% (95% CI 77
      to 85) of phenotype A less than the ratio of 3.8. The ratio was reliable for
      identifying LDL phenotype B in men and women.

PMID- 15246908
TI  - A further subgroup analysis of the effects of the DASH diet and three dietary
      sodium levels on blood pressure: results of the DASH-Sodium Trial.
AB  - This study presents an extensive analysis of the effects on blood pressure (BP)
      of changes in sodium intake over a wide array of subgroups, including joint
      subgroups defined by age and hypertension status, race or ethnicity and
      hypertension status, and gender and race or ethnicity. Participants were given 3
      levels of sodium (50, 100, and 150 mmol/2,100 kcal) for 30 days while consuming
      the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits,
      vegetables, and low-fat dairy) or a more typical American diet. Within each diet
      and subgroup, there was a general pattern such that the lower the sodium level,
      the greater the mean reduction in BP. Sodium reduction from 100 to 50 mmol/2,100
      kcal generally had twice the effect on BP as reduction from 150 to 100 mmol/2,100
      kcal. Age had a strong and graded influence on the effect of sodium within the
      typical and DASH diets, respectively: -4.8 and -1.0 mm Hg systolic for 23 to 41
      years, -5.9 and -1.8 mm Hg for 42 to 47 years, -7.5 and -4.3 mm Hg for 48 to 54
      years, and -8.1 and -6.0 mm Hg for 55 to 76 years. The influence of age on the
      effect of sodium reduction was particularly strong in nonhypertensive patients: 
      3.7 mm Hg systolic for <45 years and -7.0 mm Hg for >45 years with the typical
      diet and -0.7 and -2.8 mm Hg with the DASH diet. Reduced sodium intake and the
      DASH diet should be advocated for the prevention and treatment of high BP,
      particularly because the benefits to BP strengthen as subjects enter middle age,
      when the rate of cardiovascular disease increases sharply.

PMID- 15246909
TI  - Effects of race and health insurance on the rates of pacemaker implantation for
      complete heart block in the United States.
AB  - Although indicated for adults with complete heart block, pacemaker implantation
      is not always practiced. There are gross discrepancies by race, type of health
      insurance coverage, and size of hospital of admission in the utilization of
      pacemakers.

PMID- 15246910
TI  - Prevalence of drug-induced electrocardiographic pattern of the Brugada syndrome
      in a healthy population.
AB  - To determine the prevalence of drug-induced Brugada's syndrome (BrS)
      electrocardiograms (ECGs) in a healthy population, a sodium channel blockade
      challenge was performed in previously identified subjects with BrS-compatible
      (BrC) ECGs. These subjects were detected in 1,000 normal patients in whom first
      ECGs were systematically recorded. Because of the intermittent nature of
      electrocardiographic modifications in BrS, second ECGs were also recorded in a
      representative sample of the population presenting with first ECGs with normal
      results. The prevalence of typical drug-induced BrS ECGs was 5 of the 1,000
      patients. This value was fivefold greater than the reported prevalence of
      spontaneous BrS ECGs in the healthy population.

PMID- 15246911
TI  - Effect of radiofrequency catheter ablation on the biochemical marker ischemia
      modified albumin.
AB  - Ischemia-modified albumin (IMA) levels were measured after radiofrequency (RF)
      catheter ablation to evaluate the effect of direct myocardial necrosis on IMA
      formation. IMA levels have been shown to increase in patients after RF catheter
      ablation compared with those who undergo diagnostic electrophysiologic studies.
      The results of this study suggest that IMA may be a marker of myocardial injury.

PMID- 15246912
TI  - Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and
      endothelin-converting enzyme, on pulmonary pressures in congestive heart failure.
AB  - SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin
      converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg
      reduced pulmonary and right atrial pressures, although there was not a clear dose
      response. Systemic blood pressure, heart rate, and cardiac output were
      unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1
      levels in a dose-dependent manner, confirming NEP and ECE inhibition. The
      combined inhibition of NEP and ECE may be useful in heart failure by reducing
      right and left cardiac filling pressures.

PMID- 15246913
TI  - Prognostic importance of renal function in patients with early heart failure and
      mild left ventricular dysfunction.
AB  - We evaluated the prognostic value of renal function in an initially "untreated"
      population with mild heart failure and compared the prognosis of this population
      with a matched controlled population. During a follow-up of 13 years (mean 11.7),
      90 patients (56%) died. Mortality was higher compared with a matched controlled
      population. Multivariate Cox regression analysis demonstrated that beside the
      well-established risk markers of left ventricular ejection fraction and heart
      rate, renal function (estimated glomerular filtration rate, hazard ratio 1.16/10
      ml/min/1.73 m(2), p = 0.003) was the only additional independent predictor of
      cardiovascular mortality in patients with early heart failure.

PMID- 15246914
TI  - Magnitude of left atrial V wave is the determinant of exercise capacity in
      patients with mitral stenosis.
AB  - A large left atrial (LA) V wave can be observed in patients with pure mitral
      stenosis (MS) due to decreased LA compliance. Based on the hypothesis that
      exercise capacity may correlate with the magnitude of the LA V wave in patients
      with MS, symptom-limited exercise testing and right and left heart
      catheterization were performed in 28 patients. The results show that the
      magnitude of the LA V wave (p = 0.02) was the strongest predictor of the exercise
      duration, suggesting that LA compliance may be an important contributing factor
      in determination of exercise capacity in patients with MS.

PMID- 15246915
TI  - Clinical features of hypertrophic cardiomyopathy caused by an Arg278Cys missense
      mutation in the cardiac troponin T gene.
AB  - To further examine the genetic and clinical features of hypertrophic
      cardiomyopathy caused by mutations in the cardiac troponin T (cTnT) gene, we
      screened 143 probands from our hypertrophic cardiomyopathy population for
      mutations in this gene. We report that the Arg278Cys missense mutation in the
      cTnT gene had a different clinical presentation in 2 different families and was
      associated with a clinical profile that deviates from what is currently expected
      for cTnT gene mutations.

PMID- 15246917
TI  - Comparison of percutaneous closure of large patent ductus arteriosus by multiple
      coils versus the Amplatzer duct occluder device.
AB  - This study compared the efficacy and costs of the most used approaches for
      percutaneous closure of large patent ductus arteriosus, that is, multiple coils
      and the Amplatzer duct occluder (ADO) device. From April 2000 to September 2003,
      47 patients underwent closure of large, symptomatic patent ductus arteriosus
      (diameter 4.6 +/- 3.0 mm/m(2); QP/QS 2.1 +/- 1.9) with multiple Cook detachable
      coils (n = 19) or the ADO device (n = 28). The multiple coil approach was
      significantly cheaper (1,389 +/- 168 vs 3,811 +/- 38, p <0.0001) but as effective
      as the ADO device over a mid-term follow-up (occlusion rate 89.5% vs 96.4%, p =
      NS).

PMID- 15246916
TI  - Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha
      in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathy.
AB  - It is known from the literature that the circulating levels of tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are elevated in heart failure
      and idiopathic dilated cardiomyopathy (IDC). Few convincing data are available on
      the production of cytokines in hypertrophic cardiomyopathy (HC). The levels of
      circulating IL-6, the soluble form of the IL-6 receptor (sIL-6R), and TNF-alpha
      in 19 patients with HC, 31 patients with IDC, and 20 healthy subjects (control
      group) were examined and compared with their clinical parameters. The levels of
      TNF-alpha and circulating IL-6 proved to be elevated in the sera of patients with
      IDC. In contrast, the level of TNF-alpha was not elevated in HC, although the
      levels of IL-6 and sIL-6R were significantly higher than those in the sera of
      patients with IDC. Although elevated levels of IL-6 may correlate with the extent
      of left ventricular dysfunction in IDC, the markedly elevated IL-6 levels did not
      correlate with left ventricular function in HC. The markedly elevated TNF-alpha
      levels in IDC were associated with the elevated IL-6 levels, probably because of
      an inflammatory process and/or heart failure. In contrast, in HC, in which the
      New York Heart Association functional class was actually good, the even higher IL
      6 and sIL-6R levels were not associated with a TNF-alpha elevation. In HC, the IL
      6 and sIL-6R elevations were due to another mechanism, probably by way of the
      cardiotrophin-associated gp130 receptor. The sources of IL-6 production in HC are
      not clear yet.

PMID- 15246918
TI  - Transthoracic echocardiographic guidance of transcatheter atrial septal defect
      closure.
AB  - This study examines the safety and efficacy of transthoracic echocardiographic
      (TTE) guidance of atrial septal defect (ASD) device closure. We evaluated 74
      patients for TTE-guided ASD closure. Fifty-six patients had successful device
      implantation using TTE guidance. Twelve patients were referred for surgical ASD
      closure on the basis of TTE evaluation. Five patients with multiple ASDs or poor
      transthoracic acoustic windows had ASD device closure guided by transesophageal
      echocardiography (TEE).

PMID- 15246919
TI  - Initial experience with bosentan therapy in patients with the Eisenmenger
      syndrome.
AB  - Bosentan, an endothelin-1 antagonist that can be administered orally, has been
      shown to be effective in the treatment of idiopathic pulmonary arterial
      hypertension and may be of benefit to patients with the Eisenmenger syndrome.
      Nine patients with Eisenmenger's syndrome were treated with bosentan at a dose of
      125 mg twice a day. After treatment with bosentan, 6 of 9 patients (67%) had an
      improvement in New York Heart Assocation classification of >/=1 grades (p =
      0.03). Oxygen saturation levels increased from 79 +/- 5% to 88 +/- 6%, (p =
      0.03). The side effects of bosentan therapy were minor; no significant changes in
      liver function tests were noted. These preliminary data suggest that oral
      administration of bosentan therapy for Eisenmenger's syndrome results in improved
      oxygenation and functional status with minimal side effects.

PMID- 15246920
TI  - Quality of life and social outcomes in adults with congenital heart disease
      living in rural areas of Kentucky.
AB  - As revealed by a quality-of-life survey done in a small rural Kentucky cohort,
      adults who live in rural areas who have congenital heart disease have a
      relatively poor health-related quality of life and face unique challenges in
      gaining employment, maintaining health insurance, and overcoming the perceived
      childhood stigma of being "different."

PMID- 15246921
TI  - Relation of low bone mineral density and carotid atherosclerosis in
      postmenopausal women.
AB  - Due to the lack of convincing data about the association between atherosclerosis
      and osteoporosis, we evaluated the association between carotid atherosclerosis
      and bone mineral density in a sample of apparently healthy postmenopausal women
      who underwent health-screening in our hospital. We also evaluated a bone turnover
      marker, osteocalcin; we divided the population into 2 groups according to
      osteocalcin levels. We found a high prevalence of carotid atherosclerosis in
      subjects with high osteocalcin levels and low bone mineral density.

PMID- 15246922
TI  - Identification of professional scuba divers with patent foramen ovale at risk for
      decompression illness.
AB  - Functional and anatomic characteristics of patent foramen ovale (PFO) were
      investigated in 66 professional scuba divers (41 with and 25 without
      decompression illness) using transthoracic and transesophageal echocardiography.
      PFO with right-to-left shunting at rest is associated with decompression illness,
      particularly the neurologic type. A wider patency diameter together with a higher
      membrane mobility are associated with the risk of developing the disease in
      divers with PFO.

PMID- 15246923
TI  - Evaluation of left ventricular ejection fraction by tissue locus imaging.
AB  - The newly developed echocardiographic technique called "tissue locus imaging"
      (TLI) can visualize temporal series of images in a single picture by maintaining
      the display of previous images with a shading function; therefore, it can display
      the whole systolic shift of the mitral leaflets toward the apex in a single
      picture and can potentially offer useful information on left ventricular (LV)
      function. In 36 consecutive patients with varying degrees of LV dysfunction (15
      with coronary artery disease, 9 with cardiomyopathy, 3 with hypertension, 2 with
      aortic stenosis, 1 with aortic regurgitation, and 6 controls), the systolic shift
      of the mitral leaflets (X) by TLI showed a significant correlation with the LV
      ejection fraction (Y) by 2-dimensional echocardiography (Y = 7.2 x+13, r(2) =
      0.83, p <0.01). TLI enables the evaluation and visualization of LV systolic
      function by displaying the whole systolic shift of the mitral leaflets toward the
      apex.

PMID- 15246924
TI  - Seasonal variation of venous thromboembolic disease.

PMID- 15246925
TI  - Pseudopseudo-Brugada syndrome is a preferred term to variants of the variants of
      the Brugada syndrome.

PMID- 15246926
TI  - Effect of linear radiofrequency ablation on left atrial function.

PMID- 15246927
TI  - Congenital heart disease and abnormalities of the great vessels.

PMID- 15246928
TI  - Spatial analysis for epidemiology.
AB  - Remote sensing, geographical information systems (GIS) and spatial analysis
      provide important tools that are as yet under-exploited in the fight against
      disease. As the use of such tools becomes more accepted and prevalent in
      epidemiological studies, so our understanding of the mechanisms of disease
      systems has the potential to increase. This paper introduces a range of
      techniques used in remote sensing, GIS and spatial analysis that are relevant to
      epidemiology. Possible future directions for the application of remote sensing,
      GIS and spatial analysis are also suggested.

PMID- 15246929
TI  - Empirical modelling of government health service use by children with fevers in
      Kenya.
AB  - An understanding of spatial patterns of health facility use allows a more
      informed approach to the modelling of catchment populations. In the absence of
      patient use data, an intuitive and commonly used approach to the delineation of
      facility catchment areas is Thiessen polygons. This study presents a series of
      methods by which the validity of these assumptions can be tested directly and
      hence the suitability of a Thiessen polygon catchment model explicitly assessed.
      These methods are applied to paediatric out-patient origin data from a sample of
      81 government health facilities in four districts of Kenya. A geographical
      information system was used to predict the location of the catchment boundary
      along a transect between each pair of neighbouring facilities based on patient
      choice patterns. The mean location of boundaries between facilities of different
      type was found to be significantly displaced from the Thiessen boundary towards
      the lower-order facility. The affect of distance on within-catchment utilization
      rate was assessed by using exclusion buffers to remove the effect of neighbouring
      facilities. Utilization rate was found to exhibit a slight but steady decrease
      with distance up to 6 km from a facility. The accuracy of the future modelling of
      unsampled facility catchments can be increased by the incorporation of these
      trends.

PMID- 15246930
TI  - Creating spatially defined databases for equitable health service planning in low
      income countries: the example of Kenya.
AB  - Equity is an important criterion in evaluating health system performance.
      Developing a framework for equitable and effective resource allocation for health
      depends upon knowledge of service providers and their location in relation to the
      population they should serve. The last available map of health service providers
      in Kenya was developed in 1959. We have built a health service provider database
      from a variety of traditional government and opportunistic non-government sources
      and positioned spatially these facilities using global positioning systems, hand
      drawn maps, topographical maps and other sources. Of 6674 identified service
      providers, 3355 (50%) were private sector, employer-provided or specialist
      facilities and only 39% were registered in the Kenyan Ministry of Health database
      during 2001. Of 3319 public service facilities supported by the Ministry of
      Health, missions, not-for-profit organizations and local authorities, 84% were
      registered on a Ministry of Health database and we were able to acquire co
      ordinates for 92% of these. The ratio of public health services to population
      changed from 1:26,000 in 1959 to 1:9300 in 1999-2002. There were 82% of the
      population within 5 km of a public health facility and resident in 20% of the
      country. Our efforts to recreate a comprehensive, spatially defined list of
      health service providers has identified a number of weaknesses in existing
      national health management information systems, which with an increased
      commitment and minimal costs can be redressed. This will enable geographic
      information systems to exploit more fully facility-based morbidity data,
      population distribution and health access models to target resources and monitor
      the ability of health sector reforms to achieve equity in service provision.

PMID- 15246931
TI  - Modelling the spatial distribution of Echinococcus multilocularis infection in
      foxes.
AB  - Alveolar echinococcosis is a rare but fatal disease in humans and is caused by
      the fox tapeworm Echinococcus multilocularis. The densities of fox and grassland
      rodent populations and the interactions between them influence E. multilocularis
      transmission rates in Europe. Successful rabies control has caused fox
      populations and E. multilocularis prevalence rates to increase in many European
      countries. The potential increase of the infection pressure on the human
      population motivates the monitoring of the infection status of foxes over space
      and time. Detection of E. multilocularis antigen levels in fox faecal samples
      collected in the field might provide a pragmatic methodology for epidemiological
      surveillance of the infection status in wildlife hosts across large areas, as
      well as providing an indication of the spatial distribution of infected faeces
      contaminating the environment. In this paper, a spatial analysis of antigen
      levels detected in faeces collected in the Franche-Comte region of eastern France
      is presented. In Franche-Comte, rodent outbreaks have been observed to originate
      in areas rich in grassland. Spatial trends in fox infection levels were modelled
      here as a function of the composition ratio of grassland in the landscape derived
      from the CORINE land-cover map. Kriging models incorporating the grassland trend
      term were compared to a variety of models in which five alternative trend
      expressions were used: the alternative trend expressions included linear and
      quadratic polynomials on the x and y coordinates with and without a grassland
      term, and a constant mean model. Leave-one-out cross-validation indicated that
      the estimation errors of kriging with a trend models were significantly lower
      when the trend expression contained the grassland index term only. The
      relationship between observed and predicted antigen levels was strongest when the
      estimated range of autocorrelation was within the home range size of a single
      fox. The over-dispersion of E. multilocularis in foxes may therefore account for
      the majority of spatial autocorrelation locally, while regional trends can be
      successfully modelled as a function of habitat availability for intermediate
      hosts.

PMID- 15246932
TI  - Ecological epidemiology: landscape metrics and human alveolar echinococossis.
AB  - The larval form of the fox tapeworm Echinococcus multilocularis can cause a
      potentially fatal liver infection in human hosts. Globally rare, the disease has
      a high prevalence focus in western China. Recent research has linked landscape to
      the presence and prevalence of the disease. This paper discusses the epidemiology
      of E. multilocularis in terms of landscape and disease transmission ecology.
      Landscape form was defined using satellite imagery to create a land cover
      classification for a study site in Zhang County (Gansu Province, China).
      Following the analysis of many landscape metrics, mean shape index was found to
      be related to the prevalence of infection for 31 villages in 1975 and 1997, at
      two spatial intervals, suggesting that habitat form is a correlate of disease. A
      temporal difference shows that the landscape is no longer suitable for
      transmission. These results indicate the possibility of identifying future
      hotspots which could aid the management of the disease.

PMID- 15246933
TI  - A method for testing low-value spatial clustering for rare diseases.
AB  - This paper proposes a method that tests for the existence of low-value spatial
      clustering while accounting for the influence of high-value clustering. Although
      the method was developed in reference to the Tango test, it can be extended to
      other testing methods. The simulation results showed that the proposed method is
      able to effectively detect low-value clustering with substantially lower rates of
      type I errors than those of the Tango test, while maintaining comparable
      statistical power. Applying the method in a case study of leukemia in Minnesota
      demonstrated an overall tendency toward low-value clustering of leukemia
      mortality for males but provided inconclusive results for females.

PMID- 15246934
TI  - Identifying space-time disease clusters.
AB  - A cluster of cases of disease that are close both in space and in time is
      suggestive of an infectious aetiology. We present statistical tests for space
      time clusters of disease for the two situations where the population at risk is
      either known or unknown as a function of space and time. The tests are derived
      using standard statistical methodology from a simple mathematical model of
      disease spread, i.e. they are derived as score tests from a likelihood function
      in which the infection process is modelled as a point process whose intensity
      becomes greater near an infector. A problem for such tests is that, when
      investigating whether or not a disease may be of infectious origin, the space and
      time distances characterising closeness to an infection are very likely to be
      unknown. The proposed methodology copes with this difficulty in a statistically
      acceptable way, without requiring multiple tests whose interpretation would be
      doubtful. When the underlying population size is unknown, the test reduces to a
      modification of the Knox test. An example of its use is given as epidemiology,
      risk, space-time cluster, likelihood and Knox test.

PMID- 15246935
TI  - The role of CD4+ and CD8+ T cells in contact hypersensitivity and allergic
      contact dermatitis.
AB  - Allergic contact dermatitis (ACD) and contact hypersensitivity (CHS) are delayed
      type hypersensitivity reactions which are mediated by hapten specific T cells.
      During the sensitisation phases, both CD4+ and CD8+ T cell precursors are
      activated in the draining lymph nodes by presentation of haptenated peptides by
      skin dendritic cells. Subsequent hapten skin painting induces the recruitment of
      T cells at the site of challenge which induces inflammatory signals and apoptosis
      of epidermal cells, leading to the development of a skin inflammatory infiltrate
      and of clinical symptoms. There have been major controversies on the respective
      roles of CD4+ and CD8+ T cells in the development of the CHS inflammatory
      reaction. Experimental studies from the last 10 years have demonstrated that, in
      normal CHS responses to strong haptens, CD8+ type 1 T cells are effector cells of
      CHS while CD4+ T cells are endowed with down-regulatory functions. The latter may
      correspond to the recently described CD4+ CD25+ regulatory T cell population.
      However, in some instances, especially those where there is a deficient CD8 T
      cell pool, CD4+ T cells can be effector cells of CHS. Ongoing studies will have
      to confirm that the pathophysiology of human ACD is similar to the mouse CHS and
      that the CHS response to weak haptens, the most frequently involved in human ACD,
      is similar to that reported for strong haptens.

PMID- 15246936
TI  - Brooke-Spiegler syndrome with parotid gland involvement.
AB  - Salivary gland involvement in Brooke-Spiegler syndrome (BSS), an autosomal
      dominantly inherited disease, is known though not frequent. A case of familial
      cylindromatosis with parotid gland adenoma is herein reported. A 67-year-old lady
      presented with multiple scalp nodules and papular coalescent lesions over the
      nasolabial folds and the forehead. The clinical examination also revealed a left
      preauricular lump. Multiple biopsies of the scalp lesions and the nasolabial
      papules revealed cylindromas and trichoepitheliomas respectively. CT scan and FNA
      of the preauricular lump were suggestive of parotid gland adenoma. The patient
      underwent excision of the scalp cylindromas and total left parotidectomy. There
      is no evidence of recurrence after 4 years. The association of BSS with salivary
      gland tumours, emphasizes the necessity of thorough salivary gland examination in
      all patients with skin lesions. Knowledge of the genetic background of BSS allows
      for genetic counseling of patients.

PMID- 15246937
TI  - The alpha-defensins HNP-1 and HNP-2 are dominant self-peptides presented by HLA
      class-II molecules in lesional psoriatic skin.
AB  - Peptides bound to HLA class II molecules are involved in epidermal T-cell
      activation, an integral part in the pathogenesis of psoriasis. To characterize
      the peptide repertoire displayed, HLA class II molecules were isolated from human
      HaCaT keratinocytes and from a split skin specimen of a patient with plaque-type
      psoriasis. Human neutrophil peptides (HNP) 1 and 2, belonging to the alpha
      subfamily of defensins, were identified as dominant HLA class II bound self
      peptides by means of HPLC and subsequent electrospray ionization mass
      spectrometry in both cases. Assuming the characteristic intramolecular disulfide
      bonds remain intact, an HLA class II binding motif can be modelled for HNP-1 and 
      2. Both peptides inhibited superantigen-mediated T-cell activation in vitro. In
      conclusion, HNP-1 and -2 are dominant HLA class II bound self-peptides displayed
      by keratinocytes in psoriasis. They are capable of interfering with superantigen
      mediated T-cell activation. This might be a hint towards a possible role of alpha
      defensins in the down-regulation of inflammation.

PMID- 15246938
TI  - Leukomelanoderma following acute cutaneous graft-versus-host disease.
AB  - Acute graft versus host disease (GVHD) is characterized by a selective epithelial
      inflammation that can affect the skin, digestive tract, and liver. Development of
      pigmentary abnormalities can be observed in sites where acute cutaneous GVHD has
      occurred, and usually consists of hyperpigmented spots. We observed atypical
      pigmetary changes consisting of a combination of hyper- and hypopigmentation, so
      called leukomelanoderma, in a young allogeneic bone marrow recipient who suffered
      repetitive acute GVHD. The histopathological examinations showed features of a
      post-inflammatory process. Because keratinocytes produce inflammatory cytokines
      including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha, which
      may be implicated in the inflammatory phenomena seen in acute GVHD, we studied
      whether these inflammatory cytokines might be implicated in these pigmentary
      changes. The cytokines tested were IL-1alpha, IL-2, TNF-alpha and IL-10. The
      expression of TNF-alpha increased in the hyperpigmented skin relative to normal
      and hypopigmented skin. While TNF-alpha was variably distributed in proportion to
      different degrees of pigmentation, other molecules were detected at minimal
      levels in all samples. This observation may indicate that the production of TNF
      alpha by epidermal microenvironment may be involved in postinflammatory
      pigmentary changes.

PMID- 15246939
TI  - A new digital image analysis system useful for surface assessment of vitiligo
      lesions in transplantation studies.
AB  - So far there is no uniformity in the evaluation methods used in the assessment of
      treatment outcome in vitiligo studies. The ability to objectively measure
      surfaces of vitiligo lesions is important for both clinical practice and
      research. Our objective was to assess the reproducibility, accuracy, user
      friendliness and time effectiveness of a new digital image analysis system for
      surface measurement of vitiligo lesions. Three different observers performed both
      a visual estimation and a digital image analysis on 30 images of 10 vitiligo
      lesions. Inter- and intra-observer variation were evaluated and results were
      compared with the 2D gold standard measurements and a 3D measurement. A high
      inter- and intra-observer variability was observed for the visual estimation of
      surfaces. With the digital image analysis system a significant improvement of the
      reproducibility was achieved (p = 0.01). Moreover, results were accurate and the
      measurement procedure was user-friendly. Importantly, a systematic
      underestimation was demonstrated when comparing the 2D with the 3D measurements.
      We introduced an objective measurement method that might be useful in the future
      for consistently measuring surfaces of selected vitiligo lesions both before and
      after different therapeutic modalities.

PMID- 15246940
TI  - Lack of association between Vitamin D receptor FokI polymorphism and alopecia
      areata.
AB  - Vitamin D receptor (VDR) is expressed in the hair follicle and the lack of it
      leads to alopecia. In this study, we investigated whether there was a
      relationship between VDR FokI gene polymorphism and alopecia areata (AA). This is
      the first study investigating the relationship between VDR gene polymorphism and
      AA. Twenty-five patients with the extensive forms of AA (alopecia totalis; AT,
      alopecia universalis; AU and AT/AU) and 27 healthy control subjects were
      genotyped. Their genotypes were determined by a polymerase chain reaction (PCR)
      and restriction fragment length polymorphism analysis. The genotypes were
      classified as FF (absence of the FokI site) and ff (presence of the FokI site).
      Allele frequencies for F and f alleles were 76.0% and 24.0% in the alopecic group
      and 72.2% and 27.7% in the control group (p > 0.05). The frequencies for the FF,
      Ff and ff genotypes were 56.0%, 40.0% and 4.0% in the patient group, and 48.1%,
      48.1% and 3.7% in the control group, respectively. No statistically significant
      differences were observed in the frequencies of the VDR FokI genotype between the
      patient and the control groups. However, to conclude that there is no
      relationship between VDR gene polymorphism and AA, the VDR FokI polymorphism
      should be further studied in other populations, larger groups, and the
      distribution of other VDR polymorphisms such as BsmI, Tru9I, ApaI, TaqI and
      polyA.

PMID- 15246941
TI  - Effectiveness and side effects of UVB-phototherapy, dithranol inpatient therapy
      and a care instruction programme of short contact dithranol in moderate to severe
      psoriasis.
AB  - The efficacy of UVB-phototherapy (UVB) and dithranol treatment for psoriasis is
      well established. However, well-conducted clinical trials on the efficacy of
      dithranol are not available, making comparison between these time-honoured
      treatments with currently available therapies impossible. We studied the
      effectiveness of dithranol in a care instruction programme using short time
      exposures (short contact treatment), UVB-phototherapy and dithranol treatment in
      an inpatient setting. In an open randomised study we included 250 patients with
      moderate to severe psoriasis. The intention to treat group existed of 238
      patients. 100 patients were treated with short contact dithranol, 78 Patients
      were treated with UVB and 60 patients underwent inpatient dithranol treatment. We
      found UVB and dithranol treatment to be effective and safe in moderate to severe
      psoriasis. The efficacy of short contact dithranol treatment equals the efficacy
      of UVB-phototherapy. Dithranol treatment at the inpatient department showed
      superior efficacy in clinical response rate and treatment duration as compared to
      UVB and short contact treatment. The median number of days in remission was
      significantly longer after short contact treatment as compared to inpatient
      treatment. Although the use of dithranol is hampered by skin irritation and
      staining, the present study shows that dithranol treatment has an outstanding
      efficacy and safety profile. Comparison between different antipsoriatic
      treatments should, besides clearing capacity, reconcile duration of remission,
      safety, patient acceptability and costs.

PMID- 15246942
TI  - Successful treatment of Melkersson-Rosenthal Syndrome with lymecycline.
AB  - The cause of Melkersson-Rosenthal syndrome, a granulomatous, inflammatory disease
      is still unknown. Many treatments have been tried with variable and often
      disappointing results. We report the case of a 31-year-old woman affected by
      Melkersson-Rosenthal syndrome, who has been successfully treated with
      lymecycline, after variable results with steroids alone or combined with
      antihistamines, sulphasalazine and clofazimine.

PMID- 15246943
TI  - Digital gangrene associated with idiopathic hypereosinophilia: treatment with
      allogeneic cultured dermal substitute (CDS).
AB  - In the present case study, the patient was a 65-year-old man who suddenly
      developed purpuric and necrotic lesions with severe pain in his fingers and toes.
      Laboratory investigations revealed marked eosinophilia (77.9%), but there was no
      evidence to support a diagnosis of parasitic infections, allergic disease,
      neoplasm or connective tissue disorder. The histopathological findings did not
      show any distinct vasculitis, but there were obliterative changes of the
      arterioles. The digital gangrene gradually progressed and was unresponsive to
      corticosteroid therapy. The patient eventually underwent amputation of the distal
      phalanges. We applied allogeneic cultured dermal substitute (CDS) to the skin
      defect. The allogeneic CDS was prepared by culturing fibroblasts on a two-layered
      sponge of hyaluronic acid and atelo-collagen. This CDS is able to release a
      number of cytokines including VEGF. The present case had a good clinical result.

PMID- 15246944
TI  - Clinical evaluation of allogeneic cultured dermal substitutes for intractable
      skin ulcers after tumor resection.
AB  - Clinical research on allogeneic cultured dermal substitute (CDS), which was newly
      developed at the R&D Center for Artificial Skin of Kitasato University, has been
      carried out in medical centers across Japan with the support of the Millennium
      Project of the Ministry of Health, Labor and Welfare of Japan. Allogeneic CDS was
      prepared by cultivation of fibroblasts on a two-layered spongy matrix of
      hyaluronic acid and atelo-collagen. This paper reports the clinical results of
      application of allogeneic CDS in 12 patients with full-thickness skin defects
      after surgical resection of skin tumors. In 9 of 10 patients, healthy granulation
      tissue developed immediately, allowing us to perform split-thickness skin grafts
      at an early stage. In two cases, allogeneic CDS was used to cover an expanded
      mesh skin graft that had been applied to treat a large ulcer, and rapid
      epithelization was observed. No patient developed local infection nor local tumor
      recurrence after treatment with CDS. The spongy matrix itself as well as the
      vascular endothelial growth factor (VEGF) released by the allogeneic CDS seemed
      to be beneficial for the treatment of intractable skin ulcers. Allogeneic CDS
      functions as an excellent biological dressing, and could dramatically change the
      treatment of intractable skin ulcers.

PMID- 15246945
TI  - Management of vitiligo patients and attitude of dermatologists towards vitiligo.
AB  - As vitiligo does not cause any physical impairment, it is often considered
      unimportant by physicians. Vitiligo patients repeatedly experience disinterest
      from the medical world regarding their skin problem. A questionnaire survey was
      used to assess the management of vitiligo patients and the attitude of
      dermatologists towards vitiligo in Belgium. Vitiligo patients (n = 244) visiting
      an academic affiliated dermatology department were included and 454 out of 558
      Belgian dermatologists returned a mailed questionnaire. Vitiligo patients do not
      often visit a doctor concerning their disease and do not often treat their
      disease. Disease severity as reported by the patient is correlated with the
      number of doctor visits (p = 0.001) but not to treatment of the disease.
      Information about the treatment and physician's encouragement to treat seem
      important in motivating patients to treat their vitiligo, but 50% of the patients
      were not adequately informed about their disease and its treatment during their
      first doctor visit. Today, nearly all the dermatologists report widely informing
      their patients, but only 36% of them encourage their patients to treat their
      disease, being pessimistic concerning expected treatment results. Interestingly,
      two thirds of the patients who ever treated their disease find it worthwhile.

PMID- 15246946
TI  - Keloidal basal cell carcinoma after radiation therapy.
AB  - We report a case of keloidal basal cell carcinoma (BCC) that developed after
      radiation therapy. A 67-year-old Japanese man had received radiation therapy of
      an unknown amount for three years for the treatment of right cervical lymph node
      tuberculosis at the age of 7. Within the area of chronic radiation dermatitis, on
      the right preauricular region, he presented with a skin-colored to erythematous,
      firm nodule. Histopathologically, this nodule showed features of keloidal BCC.
      The stroma characteristically demonstrated the prominent, keloidal, thickened
      collagen bundles standing out against the surrounding actinic-damaged dermis, and
      well-circumscribed, keloidal collagen bundles that proliferated in a nodular form
      almost corresponding to a clinically firm, nodular lesion. There was no radiation
      fibrosis around the keloidal BCC. We discuss the differences between keloidal BCC
      and morpheiform BCC, and consider keloidal BCC to be a rare variant of BCC from a
      clinico- pathological basis.

PMID- 15246947
TI  - Cutaneous ulcers with type I cryoglobulinemia treated with plasmapheresis.
AB  - Severe necrotic cutaneous ulcers and kidney involvement secondary to type I
      cryoglobulinemia can be a therapeutic challenge. Plasmapheresis has been reported
      useful to treat autoimmune diseases such as thrombotic thrombocytopenic purpura,
      systemic lupus erythematosus, myasthenia gravis and Goodpasture's syndrome. We
      report the case of a patient who presented necrotic lesions with kidney
      involvement due to type I cryoglobulinemia (Ig G kappa) that evolved to a
      multiple myeloma. Treatment with high doses of corticosteroid plus
      cyclophosphamide did not control the disorder. Therapy with plasmapheresis
      produced a marked decrease in cryoglobulin levels and a subsequent relevant
      clinical improvement of cutaneous lesions and renal function. In
      cryoglobulinemia, plasmapheresis can be used as effective adjunt therapy to
      minimize cutaneous, renal and/or neurologic involvement.

PMID- 15246948
TI  - Genital porokeratosis.
AB  - We report on a negroid male suffering from porokeratosis of the scrotum.
      Porokeratosis in the genital area is rare, as is its occurrence in negroid
      people. In our patient, we found an asymptomatic non-HIV associated
      immunosuppression. In this case, the disease might be called porokeratosis of
      Mibelli. The diagnosis should be suspected in patients not belonging to one of
      the classical at-risk ethnical groups if the skin lesions seem typical.

PMID- 15246949
TI  - Perianal condyloma-like lesions in multiple myeloma associated amyloidosis.
AB  - Systemic types of amyloidosis include those associated with plasma cell
      dyscrasia, as in multiple myeloma. Here we describe a 57-year-old woman who was
      diagnosed as having multiple myeloma IgG lambda. Six months after the diagnosis
      of myeloma, mucocutaneous lesions began to develop, with ecchymoses in the body
      folds and eyelid and periorbital purpura. Pedunculated condylomatous tumours
      began to develop in the perianal area. The excisional biopsy of a perianal nodule
      revealed a faintly eosinophilic, amorphous material replacing almost the entire
      dermis, in association with ectatic, endothelial-lined vascular spaces. The
      dermal deposits showed affinity with Congo Red stain. There were no
      histopathological features typical of condylomata acuminata. A diagnosis of
      cutaneous myeloma-associated amyloidosis was established. To our knowledge, this
      is the second reported case of condyloma-like perianal lesions in multiple
      myeloma-associated amyloidosis.

PMID- 15246950
TI  - Antiepileptic drugs: indications other than epilepsy.
AB  - Antiepileptic drugs (AEDs) are increasingly used for the treatment of several non
      epileptic neurological conditions and psychiatric disorders. Most of the
      information available on the use of these agents in clinical disorders outside
      epilepsy is from case series, uncontrolled studies or small randomised clinical
      trials, and their apparent efficacy requires confirmation through well designed,
      large, phase III trials. With regard to neurological conditions other than
      epilepsy, experimental evidence for the efficacy of AEDs is only available for
      the treatment of patients with trigeminal neuralgia, neuropathic pain syndromes,
      migraine and essential tremor. Carbamazepine is commonly prescribed as first-line
      therapy for patients with trigeminal neuralgia. Gabapentin has been recently
      marketed for the management of neuropathic pain syndromes, particularly diabetic
      neuropathy and postherpetic neuralgia. Valproic acid (sodium valproate), in the
      form of divalproex sodium, is approved for migraine prophylaxis. Primidone can be
      considered a valuable option for the treatment of essential tremor. AEDs are also
      used to treat psychiatric conditions, in particular bipolar disorder. So far, the
      most commonly utilized AEDs in the treatment of this disorder have been
      carbamazepine and valproic acid, which have showed an antimanic efficacy and a
      probable long-term, mood-stabilizing effect in many bipolar patients, including
      those refractory or intolerant to lithium. The availability of a new generation
      of AEDs has broadened the therapeutic options in bipolar disorder. Lamotrigine,
      oxcarbazepine, gabapentin and topiramate appear to be promising in the treatment
      of refractory bipolar disorder, as a monotherapy as well as in combination with
      traditional mood stabilizers. In addition, newer AEDs appear to have a more
      favourable tolerability and drug interaction profile as compared to older
      compounds, so thus improving compliance to treatment.

PMID- 15246951
TI  - A critical review of the different conceptual hypotheses framing human focal
      epilepsy.
AB  - In the attempt to understand the processes affecting human focal epilepsy,
      various models that have been proposed as a back drop to which current
      observations of the clinical manifestations and therapies in this disorder can be
      tested. There are three main models that are reviewed. The notion of
      epileptogenicity as described by Penfield and Jasper's epileptogenic zone model
      postulates that specific regions of cerebral cortex have varying degrees of
      importance in the generation of focal epilepsy. A variation of this hypothesis
      comprises the second model put forth by Talairach and Bancaud. In this view the
      notion of the epileptogenic zone is expanded to incorporate a larger regions of
      cerebral cortex involved in the seizure propagation. A third concept and more
      separate hypothesis suggests that all components of the neural network involved
      in focal epilepsy are equally importance in the initiation and maintenance of the
      seizure. The various concepts underlying these models are reviewed in this paper
      and data from clinical and neurophysiologic observations are discussed in the
      context of these models. We suggest in this paper that the data best supports the
      epileptogenic zone hypothesis put forth by Penfield and Jasper.

PMID- 15246952
TI  - Hypocalcemic generalised seizures as a manifestation of iatrogenic
      hypoparathyroidism months to years after thyroid surgery.
AB  - Hypoparathyroidism is a relatively common side effect of a thyroidectomy and
      leads to hypocalcemia. Carpopedal spasm and tetany are typical manifestations and
      usually occur within weeks after surgery. The first signs can be less typical and
      include movement disorders such as chorea, as well as symptoms of increased
      intracranial pressure or epileptic seizures. We describe two cases with
      generalised tonic-clonic seizures as the first manifestation of postoperative
      hypoparathyroidism, appearing months and years after thyroidectomy. Iatrogenic
      hypoparathyroidism needs to be considered in the differential diagnosis of adult
      onset, generalised, tonic-clonic seizures even if the thyroidectomy was performed
      years earlier.

PMID- 15246953
TI  - Factors underlying scalp-EEG interictal epileptiform discharges in intractable
      frontal lobe epilepsy.
AB  - AIMS: Scalp-EEG interictal epileptiform discharges (IEDs) may be less predictive
      of the outcome of frontal lobe epilepsy surgery than of temporal lobe epilepsy
      surgery. We identified factors associated with the location of scalp-EEG IEDs in
      intractable frontal lobe epilepsy. METHODS: Ten factors were assessed in a
      retrospective review of 53 patients with either concordant (frontal lobe seizure
      focus) or discordant (generalized or outside frontal seizure focus) IED or both,
      who had excellent surgical outcomes. The Fisher exact test and the Wilcoxon rank
      sum test determined statistically significant associations. RESULTS: Thirty-six
      patients (68%) had concordant IED, 24 (45%) discordant IED, and 17 (32%) both.
      Younger age at onset was significantly associated with discordant IED (mean, 7.5
      years versus 17 years for patients without discordant IED; P < 0.01), whereas
      duration of epilepsy was not. Seizure foci at the frontal convexity were
      associated with concordant IED. About 72% of patients with a convexity seizure
      focus had concordant IED, compared with only 33% of patients with mesial frontal
      foci having concordant IED (P = 0.06). CONCLUSIONS: Early seizure onset in
      intractable frontal lobe epilepsy is associated with IEDs discordant with seizure
      focus. Frontal convexity seizure foci are more likely than mesial frontal seizure
      foci to be associated with concordant discharges.

PMID- 15246954
TI  - Palliative temporal resection for the treatment of intractable bioccipital
      epilepsy.
AB  - RATIONALE: Temporal resection is usually ineffective in patients with occipital
      seizures. However, when seizures are unilateral occipital resections are now,
      occasionally, considered. When bilateral seizures and visual field defects exist,
      occipital resection can not be carried out. When predominantly lateralized,
      temporal seizure onset can be shown in such patients, palliative temporal
      resection may be justified. METHODS: We report two patients with medically
      refractory, bilateral occipital lobe seizures. Clinical and electrophysiological
      patterns suggested consistent spread of the ictal discharge to temporal lobe
      structures. Long-term EEG video monitoring was followed by
      stereoelectroencephalography (SEEG) to assess involvement of temporal and
      occipital regions symmetrically. RESULTS: Both patients had non-lateralized,
      elementary visual aura followed by loss of contact, automatisms, frequent falls
      and occasionally secondary generalization. Brain MR imaging revealed bilateral
      parieto-occipital ischemic lesions without concomitant temporal volumetric
      abnormalities. They had bilateral or unilateral visual field defects. Scalp EEGs
      showed bilateral temporal or temporo-parieto-occipital interictal and ictal
      epileptic abnormalities. Intracranial SEEG recordings confirmed the presence of
      multifocal, temporo-occipital epileptic abnormalities. In both however, disabling
      seizures originated in, or rapidly spread to the right hippocampus. Since
      occipital resections were inadvisable, both patients underwent selective, right
      amygdalohippocampectomy. Seizures continued in both (two-year follow-up), but
      were much less severe, not associated with falling or secondary generalization,
      not followed by fatigue or headache and with faster recovery. CONCLUSION: When
      occipital resection is inadvisable because of bilateral or diffuse visual
      problems, palliative temporal resection may be considered in patients with
      lesional, bilateral occipital lobe epilepsy, and rapid seizure spread to mesial
      temporal structures. (Published with videosequences).

PMID- 15246955
TI  - Temporal lobe dysembryoplastic neuroepithelial tumour: significance of discordant
      interictal spikes.
AB  - PURPOSE: Dysembryoplastic neuroepithelial tumours (DNET) are an important cause
      of refractory partial epilepsies. They usually occur within dysplastic cortex and
      tend to affect the temporal lobes. The EEG of these patients is characterised by
      slowing and/or epileptiform abnormalities with a multifocal distribution. We
      studied the EEG features of epilepsy patients with a temporal lobe DNET to assess
      the relationship of EEG abnormalities with the localisation of the tumour and the
      clinical features. METHODS: We retrospectively reviewed 16 patients with
      unilateral, temporal lobe DNET on MRI. The EEG abnormalities were classified as
      concordant to the lesion when the EEG discharges were confined to the ipsilateral
      temporal lobe or discordant when EEG discharges were found in other areas.
      Clinical and epilepsy characteristics were compared between patients with
      concordant and discordant EEG. RESULTS: Focal EEG abnormalities were found in 81%
      of the patients; 6/16 patients had concordant EEG abnormalities, and 7/16
      patients had discordant EEG abnormalities. Epilepsy severity prior to the
      operation, antecedents and post-operative outcome were not different between
      patients with concordant or discordant EEG abnormalities. CONCLUSION: Patients
      with temporal lobe DNET often show EEG discharges discordant to the tumour.
      However, they do not appear to predict the clinical and epilepsy characteristics
      of these patients.

PMID- 15246956
TI  - Memory function decline over 18 months after selective amygdalohippocampectomy.
AB  - We report on a 22 year-old woman with left temporal lobe epilepsy who had
      suffered complex partial seizures since childhood. At 19 years 10 months of age
      she underwent selective amygdalohippocampectomy, which resulted in a complete
      cessation of seizures. Preoperatively, the Logical Memory II section of the WMS-R
      revealed poor logical memory function. Postoperatively, the patient's scores on
      several neuropsychological tests had deteriorated, namely, the Miyake Paired
      Associate Word Learning Test (related and unrelated pairs), several sections of
      the WMS-R (Figural Memory, Logical memory I, Visual Reproduction II, Visual
      Paired Associates I, and Verbal Paired Associates I and II), and the BVRT-R. In
      particular, her scores on the Visual Paired Associates I, Verbal Paired
      Associates I and II sections of the WMS-R, and the BVRT-R not only declined at
      one and three months post-surgery, but also showed progressive deterioration at
      16 and 18 months post-surgery. It should be kept in mind that selective
      amygdalohippocampectomy can result in progressive postoperative, deterioration in
      some aspects of memory function.

PMID- 15246957
TI  - Panayiotopoulos syndrome: video-EEG illustration of a typical seizure.
AB  - Panayiotopoulos syndrome (PS) is a form of idiopathic, partial epilepsy of
      childhood with a high prevalence rate, but with poor clinical recognition,
      possibly due to the characteristics of the seizure, which not infrequently lack
      common epileptic motor and/or sensory phenomena. Instead, autonomic symptoms such
      as retching and vomiting, predominate. Semiological knowledge of the seizures in
      PS depends mainly on parental observations, but not enough ictal-EEG data are
      available, possibly due to the rarity of seizures. In addition to previous
      knowledge regarding the occipital onset of seizures in PS, it has been recognized
      that other areas, mainly the frontal regions, may be involved. The present report
      demonstrates the video-EEG findings of a seizure in a patient with PS.
      Subclinical ictal EEG discharges with occipital onset precede the clinical
      autonomic symptoms; eye deviation which is typical of occipital involvement,
      appears in later sequences. These findings suggest that at least for certain
      seizures an occipital origin may be considered, even in seizures without the
      early manifestations typical of this region. (Published with videosequences).

PMID- 15246958
TI  - Paroxysmal autonomic alterations mimicking epilepsy: a case report.
AB  - A 22-year-old male patient presented with paroxysmal hyperhidrosis, mydriasis,
      hypertension, and tachycardia. Cranial and cervical MRI revealed focal atrophy in
      the high order zone of the central autonomic network and syringomyelia. His
      physical and neurological examinations were unremarkable. Physiological testing
      included EEG, SPECT, serum/urine tests and autonomic testing. A poor response was
      achieved with the medical and interventional procedures employed. As the central
      autonomic network is an integral component of the internal regulation system of
      the brain, any lesion, no matter where in the network, may lead to paroxysmal
      autonomic alterations mimicking epilepsy (Published with videosequences).

PMID- 15246959
TI  - Oxysterols from human bile induce apoptosis of canine gallbladder epithelial
      cells in monolayer culture.
AB  - Oxysterols have been detected in various mammalian organs and blood. Biliary
      epithelium is exposed to high concentrations of cholesterol, and we have
      identified three keto-oxysterols (cholest-4-en-3-one, cholesta-4,6-dien-3-one,
      cholesta-3,5-dien-7-one) in human bile and gallstones. Because the effects of
      oxysterols on biliary physiology are not well defined, we investigated their
      biological effects on dog gallbladder epithelial cells. Enriched medium (culture
      medium containing taurocholate and lecithin and cholesterol +/- various
      oxysterols) was applied to confluent monolayers of dog gallbladder epithelial
      cells in culture. Cytotoxicity and apoptosis were studied by morphological
      analysis and flow cytometry. Oxysterols in the mitochondrial fraction were
      identified by gas chromatography/mass spectrometry, whereas release of cytochrome
      c from mitochondria was assayed by spectrophotometry and Western blot analysis.
      Compared with cells treated with culture medium or with enriched medium
      containing cholesterol, oxysterol-treated cells showed significantly increased
      apoptosis (P < 0.05). Exogenously applied oxysterols were recovered from the
      mitochondrial fraction. Cytochrome c release from mitochondria was increased
      significantly by cholest-4-en-3-one, cholesta-4,6-dien-3-one, and 5beta-cholestan
      3-one (all P < 0.05). Thus oxysterols recovered from human bile and gallstones
      induce apoptosis of biliary epithelium via a mitochondrial-dependent pathway and
      may play a role in the pathogenesis of chronic inflammation and carcinogenesis in
      the gallbladder.

PMID- 15246960
TI  - Neutrophil elastase contributes to the development of ischemia-reperfusion
      induced liver injury by decreasing endothelial production of prostacyclin in
      rats.
AB  - We previously reported that nitric oxide (NO) derived from endothelial NO
      synthase (NOS) increased endothelial prostacyclin (PGI(2)) production in rats
      subjected to hepatic ischemia-reperfusion (I/R). The present study was undertaken
      to determine whether neutrophil elastase (NE) decreases endothelial production of
      PGI(2), thereby contributing to the development of I/R-induced liver injury by
      decreasing hepatic tissue blood flow in rats. Hepatic tissue levels of 6-keto
      PGF(1alpha), a stable metabolite of PGI(2), were transiently increased and peaked
      at 1 h after reperfusion, followed by a gradual decrease until 3 h after
      reperfusion. Sivelestat sodium hydrochloride and L-658,758, two NE inhibitors,
      reduced I/R-induced liver injury. These substances inhibited the decreases in
      hepatic tissue levels of 6-keto-PGF(1alpha) at 2 and 3 h after reperfusion but
      did not affect the levels at 1 h after reperfusion. These NE inhibitors
      significantly increased hepatic tissue blood flow from 1 to 3 h after
      reperfusion. Both hepatic I/R-induced increases in the accumulation of
      neutrophils and the microvascular permeability were inhibited by these two NE
      inhibitors. Protective effects induced by the two NE inhibitors were completely
      reversed by pretreatment with nitro-l-arginine methyl ester, an inhibitor of NOS,
      or indomethacin. Administration of iloprost, a stable derivative of PGI(2),
      produced effects similar to those induced by NE inhibitors. These observations
      strongly suggest that NE might play a critical role in the development of I/R
      induced liver injury by decreasing endothelial production of NO and PGI(2),
      leading to a decrease in hepatic tissue blood flow resulting from inhibition of
      vasodilation and induction of activated neutrophil-induced microvascular injury.

PMID- 15246961
TI  - Regulated production of the chemokine CCL28 in human colon epithelium.
AB  - The chemokine CCL28 is constitutively expressed by epithelial cells at several
      mucosal sites and is thought to function as a homeostatic chemoattractant of
      subpopulations of T cells and IgA B cells and to mediate antimicrobial activity.
      We report herein on the regulation of CCL28 in human colon epithelium by the
      proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of
      microbial metabolism. In vivo, CCL28 was markedly increased in the epithelium of
      pathologically inflamed compared with normal human colon. Human colon and small
      intestinal xenografts were used to model human intestinal epithelium in vivo.
      Xenografts constitutively expressed little, if any, CCL28 mRNA or protein. After
      stimulation with the proinflammatory cytokine IL-1, CCL28 mRNA and protein were
      significantly increased in the epithelium of colon but not small intestinal
      xenografts, although both upregulated the expression of another prototypic
      chemokine, CXCL8, in response to the identical stimulus. In studies of CCL28
      regulation using human colon epithelial cell lines, proinflammatory stimuli,
      including IL-1, bacterial flagellin, and bacterial infection, significantly
      upregulated CCL28 mRNA expression and protein production. In addition, CCL28 mRNA
      expression and protein secretion by those cells were significantly increased by
      the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated
      upregulation of CCL28 by colon epithelial cells was synergistically increased by
      pretreatment of cells with n-butyrate. Consistent with its upregulated expression
      by proinflammatory stimuli, CCL28 mRNA expression was attenuated by
      pharmacological inhibitors of NF-kappaB activation. These findings indicate that
      CCL28 functions as an "inflammatory" chemokine in human colon epithelium and
      suggest the notion that CCL28 may act to counterregulate colonic inflammation.

PMID- 15246962
TI  - IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via
      induction of multiple chemokines and adhesion molecules: a critical role of IRF
      1.
AB  - We have previously shown that IFN-gamma/STAT1 plays an essential role in
      concanavalin A (ConA)-induced T cell hepatitis via activation of apoptotic
      signaling pathways. Here we demonstrate that IFN-gamma/STAT1 also plays a crucial
      role in leukocyte infiltration into the liver in T cell hepatitis. After
      injection of ConA, leukocytes were significantly infiltrated into the liver,
      which was suppressed in IFN-gamma(-/-) and STAT1(-/-) mice. Disruption of the IFN
      regulatory factor-1 (IRF-1) gene, a downstream target of IFN-gamma/STAT1,
      abolished ConA-induced liver injury and suppressed leukocyte infiltration into
      the liver. Additionally, ConA injection induced expression of a wide variety of
      chemokines and adhesion molecules in the liver. Among them, expression of ICAM-1,
      VCAM-1, monokine induced by IFN-gamma (Mig), CC chemokine ligand-20, epithelial
      cell-derived neutrophil-activating peptide (ENA)-78, IFN-inducible T cell-alpha
      chemoattractant (I-TAC), and IFN-inducible protein-10 (IP-10) was markedly
      attenuated in IFN-gamma(-/-), STAT1(-/-), and IRF-1(-/-) mice. In primary mouse
      hepatocytes, Kupffer cells, and endothelial cells, in vitro treatment with IFN
      gamma activated STAT1, STAT3, and IRF-1, and induced expression of VCAM-1, ICAM
      1, Mig, ENA-78, I-TAC, and IP-10 mRNA. Induction of these chemokines and adhesion
      molecules was markedly diminished in STAT1(-/-) and IRF-1(-/-) hepatic cells
      compared with wild-type hepatic cells. These findings suggest that in addition to
      induction of apoptosis, previously well documented, IFN-gamma also stimulated
      hepatocytes, sinusoidal endothelial cells, and Kupffer cells partly via an
      STAT1/IRF-1-dependent mechanism to produce multiple chemokines and adhesive
      molecules responsible for promoting infiltration of leukocytes and, ultimately,
      resulting in hepatitis.

PMID- 15246963
TI  - TGF-beta1 modulates matrix metalloproteinase-13 expression in hepatic stellate
      cells by complex mechanisms involving p38MAPK, PI3-kinase, AKT, and p70S6k.
AB  - Transforming growth factor-beta1 (TGF-beta1), the main cytokine involved in liver
      fibrogenesis, induces expression of the type I collagen genes in hepatic stellate
      cells by a transcriptional mechanism, which is hydrogen peroxide and de novo
      protein synthesis dependent. Our recent studies have revealed that expression of
      type I collagen and matrix metalloproteinase-13 (MMP-13) mRNAs in hepatic
      stellate cells is reciprocally modulated. Because TGF-beta1 induces a transient
      elevation of alpha1(I) collagen mRNA, we investigated whether this cytokine was
      able to induce the expression of MMP-13 mRNA during the downfall of the alpha1(I)
      collagen mRNA. In the present study, we report that TGF-beta1 induces a rapid
      decline in steady-state levels of MMP-13 mRNA at the time that it induces the
      expression of alpha1(I) collagen mRNA. This change in MMP-13 mRNA expression
      occurs within the first 6 h postcytokine administration and is accompanied by a
      twofold increase in gene transcription and a fivefold decrease in mRNA half-life.
      This is followed by increased expression of MMP-13 mRNA, which reaches maximal
      values by 48 h. Our results also show that this TGF-beta1-mediated effect is de
      novo protein synthesis-dependent and requires the activity of p38MAPK,
      phosphatidylinositol 3-kinase, AKT, and p70(S6k). Altogether, our data suggest
      that regulation of MMP-13 by TGF-beta1 is a complex process involving
      transcriptional and posttranscriptional mechanisms.

PMID- 15246965
TI  - Recent advances in alcoholic liver disease III. Role of the innate immune
      response in alcoholic hepatitis.
AB  - Ethanol consumption is known to cause significant acute liver damage resulting in
      hepatic fibrosis and eventual cirrhosis when consumed chronically. The
      mechanism(s) by which ethanol exerts its damaging effects on the liver are not
      well understood; however, recent scientific investigation has begun to delineate
      the earliest events in alcoholic liver disease. From these studies, it is
      apparent that components of the innate immune system and, in particular, Kupffer
      cells, play a significant role in this process. It is also becoming clear that
      other parts of the immune system including T cells may also be responsible for
      mediating the devastating effects of chronic alcohol consumption on the liver.
      This review will highlight recent experiments demonstrating a role for the innate
      immune response in the initiation and progression of alcohol-induced liver
      hepatitis and subsequent organ damage.

PMID- 15246966
TI  - Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer.
AB  - Pancreatic inflammation appears to increase the risk of pancreatic cancer. This
      observation is striking in the hereditary pancreatitis kindreds but also occurs
      in alcoholic, idiopathic, and tropical chronic pancreatitis and cystic fibrosis.
      However, the mutations associated with hereditary pancreatitis or cystic fibrosis
      are not found in sporadic pancreatic adenocarcinomas, suggesting that the effects
      are indirect by causing recurrent pancreatitis and chronic inflammation. The
      process of mutation accumulation and clonal expansion that is required for
      development of invasive pancreatic adenocarcinoma must therefore be accelerated
      in chronic pancreatitis to account for the high incidence of pancreatic cancer in
      these patients.

PMID- 15246967
TI  - CD4+ T cells from IL-10-deficient mice transfer susceptibility to NSAID-induced
      Rag colitis.
AB  - Products of arachidonic acid metabolism are important for mucosal homeostasis,
      because blockade of this pathway with an NSAID triggers rapid onset of severe
      colitis in the IL-10 knockout (IL-10(-/-)) model of IBD. Rag mice do not make T
      or B cells. This study determined whether reconstitution of Rag mice with T cells
      from IL-10(-/-) mice transferred NSAID colitis susceptibility. Rag mice were
      reconstituted by intraperitoneal injection with splenocytes from wild-type (WT)
      or IL-10(-/-) animals. Colitis was induced by using piroxicam and was graded
      histologically. Isolated lamina propria mononuclear cells (LPMC), lamina propria
      T cells, and LPMC depleted of T cells from reconstituted Rag mice were studied
      for cytokine production. Only animals reconstituted with IL-10(-/-) CD4(+) T
      cells and administered piroxicam developed severe colitis. LPMC from these
      colitic animals made IFN-gamma, whose production was dependent on T cells. Some
      IL-10 was produced but only from non-T cells. LPMC from the healthy Rag mice that
      were reconstituted with WT T cells and were piroxicam resistant made much more IL
      10. This was mostly T cell dependent. In conclusion, only CD4(+) T cells from IL
      10(-/-) animals leave Rag mice susceptible to NSAID-induced, Th1 colitis. Lamina
      propria T cells normally make large quantities of IL-10, suggesting that IL-10
      from T cells may be protective.

PMID- 15246968
TI  - Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric
      functions in healthy volunteers.
AB  - CCK influences satiation and gastric and gallbladder emptying. GI181771X is a
      novel oral CCK-1 agonist; its effects on gastric emptying of solids,
      accommodation, and postprandial symptoms are unclear. Effects of four dose levels
      of the oral CCK-1 agonist GI181771X and placebo on gastric functions and
      postprandial symptoms were compared in 61 healthy men and women in a randomized,
      gender-stratified, double-blind, double-dummy placebo-controlled, parallel group
      study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of
      GI181771X on gastric emptying of solids by scintigraphy, gastric volume by
      (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated
      volume of Ensure, and postprandial nausea, bloating, fullness, and pain were
      studied. On each of 3 study days, participants received their randomly assigned
      treatment. Adverse effects and safety were monitored. There were overall group
      effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial
      volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of
      GI181771X significantly delayed gastric emptying of solids (P < 0.01) and
      increased fasting (P = 0.035) gastric volumes without altering postprandial (P =
      0.056) gastric volumes or postprandial symptoms relative to placebo. The effect
      of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P
      = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4
      h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg
      solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and
      occurred in a minority of participants. GI181771X delays gastric emptying of
      solids and exhibits an acceptable safety profile in healthy participants. CCK-1
      receptors can be modulated to increase fasting gastric volume.

PMID- 15246969
TI  - Absence of increasing cortical fMRI activity volume in response to increasing
      visceral stimulation in IBS patients.
AB  - Cerebral cortical activity associated with perceived visceral sensation
      represents registration of afferent transduction and cognitive processes related
      to perception. Abnormalities of gut sensory function can involve either or both
      of these processes. Cortical registration of subliminal viscerosensory signals
      represents cerebral cortical activity induced by stimulation of intestinal
      sensory neurocircuitry without the influence of perception-related cortical
      activity, whereas those associated with perception represent both neural
      circuitry and cognitive processes. Our aims were to determine and compare
      quantitatively cerebral cortical functional magnetic resonance imaging (fMRI)
      activity in response to subliminal, liminal, and nonpainful supraliminal rectal
      distension between a group of irritable bowel syndrome (IBS) patients and
      age/gender-matched controls. Eight female IBS patients and eight age-matched
      healthy female control subjects were studied using brain fMRI techniques. Three
      barostat-controlled distension levels were tested: 1) 10 mmHg below perception
      (subliminal), 2) at perception (liminal), and 3) 10 mmHg above perception
      (supraliminal). In control subjects, there was a direct relationship between
      stimulus intensity and cortical activity volumes, ie., the volume of fMRI
      cortical activity in response to subliminal (3,226 +/- 335 microl), liminal
      (5,751 +/- 396 microl), and supraliminal nonpainful stimulation (8,246 +/- 624
      microl) were significantly different (P < 0.05). In contrast, in IBS patients
      this relationship was absent and fMRI activity volumes for subliminal (2,985 +/-
      332 microl), liminal (2,457 +/- 342 microl), and supraliminal nonpainful
      stimulation (2,493 +/- 351 microl) were similar. Additional recruitment of
      cortical fMRI activity volume in response to increasing stimulation from
      subliminal to liminal and supraliminal domains is absent in IBS patients,
      suggesting a difference in the processing of perceived stimulation compared with
      controls.

PMID- 15246970
TI  - Cyclooxygenase-2-regulated vascular endothelial growth factor release in gastric
      fibroblasts.
AB  - VEGF is a highly specific stimulator of endothelial cells and may play an
      important role in angiogenesis in the process of tissue regeneration. We
      previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of
      the ulcer bed is involved in the ulcer repair process. To clarify the role of COX
      2 in angiogenesis during gastric ulcer healing, we investigated the relation
      between COX-2 expression and VEGF production in human gastric fibroblasts in vivo
      and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL
      1alpha or IL-1beta in the presence or absence of NS-398, a selective COX-2
      inhibitor. Supernatant VEGF and PGE(2) concentrations were measured by enzyme
      linked immunosorbent assay. COX-2 expression in fibroblasts was determined by
      Western blot analysis. VEGF and COX-2 expression in surgical resections of human
      gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently
      enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation.
      IL-1 also stimulated PGE(2) production in gastric fibroblasts via COX-2
      induction. NS-398 significantly suppressed VEGF and PGE(2) release from IL-1
      stimulated gastric fibroblasts; concurrent addition of PGE(2) restored NS-398
      inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in
      fibroblast-like cells in the ulcer bed of gastric tissues. These results suggest
      that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated
      by IL-1 in vitro and that angiogenesis induced by the COX-2-VEGF pathway might be
      involved in gastric ulcer healing.

PMID- 15246971
TI  - Protective effect of endogenous PPARgamma against acute gastric mucosal lesions
      associated with ischemia-reperfusion.
AB  - Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal
      bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor
      gamma (PPARgamma), a member of a nuclear receptor family, functions as an
      endogenous anti-inflammatory pathway in a murine model of AGML induced by
      ischemia-reperfusion (I/R). Treatment with specific PPARgamma ligands such as BRL
      49653, pioglitazone, or troglitazone was examined in a model of AGML induced by
      I/R. PPARgamma-deficient and wild-type mice were also examined for their response
      to I/R in stomach. Specific PPARgamma ligands exhibited dramatic and rapid
      protection against AGML formation associated with I/R in mice in a dose-dependent
      manner. In contrast, the AGML induced by I/R in PPARgamma-deficient mice was more
      severe than that observed in wild-type mice. Administration of the PPARgamma
      ligand significantly inhibited the upregulation of TNF-alpha, ICAM-1, inducible
      nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in
      the stomach. These data indicate that an endogenous pathway associated with
      PPARgamma plays an important role in the pathogenesis of I/R-associated injury in
      the stomach.

PMID- 15246972
TI  - cAMP targeting of p38 MAP kinase inhibits thrombin-induced NF-kappaB activation
      and ICAM-1 expression in endothelial cells.
AB  - We investigated the mechanisms by which elevated intracellular cAMP concentration
      inhibits the thrombin-induced ICAM-1 expression in endothelial cells. Exposure of
      human umbilical vein endothelial cells to forskolin or dibutyryl cAMP, which
      increase intracellular cAMP by separate mechanisms, inhibited the thrombin
      induced ICAM-1 expression. This effect of cAMP was secondary to inhibition of NF
      kappaB activity, the key regulator of thrombin-induced ICAM-1 expression in
      endothelial cells. The action of cAMP occurred downstream of IkappaBalpha
      degradation and was independent of NF-kappaB binding to the ICAM-1 promoter. We
      observed that cAMP interfered with thrombin-induced phosphorylation of NF-kappaB
      p65 (RelA) subunit, a crucial event promoting the activation of the DNA-bound NF
      kappaB. Because p38 MAPK can induce transcriptional activity of RelA/p65 without
      altering the DNA binding function of NF-kappaB, we addressed the possibility that
      cAMP antagonizes thrombin-induced NF-kappaB activity and ICAM-1 expression by
      preventing the activation of p38 MAPK. We observed that treating cells with
      forskolin blocked the activation of p38 MAPK, and inhibition of p38 MAPK
      interfered with phosphorylation of RelA/p65 induced by thrombin. Our data
      demonstrate that increased intracellular cAMP concentration in endothelial cells
      prevents thrombin-induced ICAM-1 expression by inhibiting p38 MAPK activation,
      which in turn prevents phosphorylation of RelA/p65 and transcriptional activity
      of the bound NF-kappaB.

PMID- 15246973
TI  - Viscoelasticity of human alveolar epithelial cells subjected to stretch.
AB  - Alveolar epithelial cells undergo stretching during breathing and mechanical
      ventilation. Stretch can modify cell viscoelastic properties, which may
      compromise the balance of forces in the alveolar epithelium. We studied the
      viscoelasticity of alveolar epithelial cells (A549) subjected to equibiaxial
      distention with a novel experimental approach. Cells were cultured on flexible
      substrates and subjected to stepwise deformations of up to 17% with a device
      built on an inverted microscope. Simultaneously, cell storage (G') and loss (G'')
      moduli were measured (0.1-100 Hz) with optical magnetic twisting cytometry. G'
      and G'' increased with strain up to 64 and 30%, respectively, resulting in a
      decrease in G''/G' (15%). This stretch-induced response was inhibited by
      disruption of the actin cytoskeleton with latrunculin A. G' increased with
      frequency following a power law with exponent alpha = 0.197. G'' increased
      proportionally to G' but exhibited a more marked frequency dependence at high
      frequencies. Stretching (14%) caused a fall in alpha (13%). At high stretching
      amplitudes, actual cell strain (14.4%) was lower than the applied substrate
      strain (17.3%), which could indicate a partial cell detachment. These data
      suggest that cytoskeletal prestress modulates the elastic and frictional
      properties of alveolar epithelial cells in a coupled manner, according to soft
      glassy rheology. Stretch-induced cell stiffening could compromise the balance of
      forces at the cell-cell and cell-matrix adhesions.

PMID- 15246974
TI  - Variability in preterm lamb lung mechanics after intra-amniotic endotoxin is
      associated with changes in surfactant pool size and morphometry.
AB  - Antenatal exposure to intra-amniotic (i.a.) endotoxin initiates a complex series
      of events, including an inflammatory cascade, increased surfactant production,
      and alterations to lung structure. Using the low frequency forced oscillation
      technique as a sensitive tool for measurement of respiratory impedance, we aimed
      to determine which factors contributed most to measured changes in lung
      mechanics. Respiratory impedance data obtained from sedated preterm lambs exposed
      to either i.a. injection with saline or 20 mg of endotoxin 1, 2, 4, and 15 days
      before delivery at 125 days gestation were studied, and association with indexes
      of standard lung morphometry, inflammatory response, and alveolar surfactant
      saturated phosphatidylcholine (Sat PC) pool size was demonstrated. Reduction in
      tissue impedance with increasing interval between exposure and delivery was
      evident as early as 4 days after i.a. endotoxin injection, coinciding with
      resolution of inflammatory reaction, increased alveolar surfactant pools, and
      contribution of alveolar ducts to the parenchymal fraction, and a later decrease
      in the tissue component of the parenchymal fraction. Decreases in tissue damping
      (resistance) were more marked than decreases in tissue elastance. Log alveolar
      Sat PC accounted for most variability in tissue damping (88.9%) and tissue
      elastance (73.4%), whereas tissue fraction contributed 2 and 6.4%, respectively.
      The alveolar Sat PC pool size was the sole factor contributing to change in
      tissue hysteresivity. No changes were observed in airway resistance. Despite the
      complex cascade of events initiated by antenatal endotoxin exposure, variability
      in lung tissue mechanics is associated primarily with changes in alveolar Sat PC
      pool and lung morphology.

PMID- 15246975
TI  - Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in
      JME/CF15 cells, a cystic fibrosis airway epithelial cell line.
AB  - Prostasin is a tryptic peptidase expressed in prostate, kidney, lung, and airway.
      Mammalian prostasins are related to Xenopus channel-activating protease, which
      stimulates epithelial Na+ channel (ENaC) activity in frogs. In human epithelia,
      prostasin is one of several membrane peptidases proposed to regulate ENaC. This
      study tests the hypothesis that prostasin can regulate ENaC in cystic fibrosis
      epithelia in which excessive Na+ uptake contributes to salt and water imbalance.
      We show that prostasin mRNA and protein are strongly expressed by human airway
      epithelial cell lines, including immortalized JME/CF15 nasal epithelial cells
      homozygous for the DeltaF508 cystic fibrosis mutation. Epithelial cells
      transfected with vectors encoding recombinant soluble prostasin secrete active,
      tryptic peptidase that is highly sensitive to inactivation by aprotinin. When
      studied as monolayers in Ussing chambers, JME/CF15 cells exhibit amiloride
      sensitive, transepithelial Na+ currents that are markedly diminished by
      aprotinin, suggesting regulation by serine-class peptidases. Overproduction of
      membrane-anchored prostasin in transfected JME/CF15 cells does not augment Na+
      currents, and trypsin-induced increases are small, suggesting that baseline
      serine peptidase-dependent ENaC activation is maximal in these cells. To probe
      prostasin's involvement in basal ENaC activity, we silenced expression of
      prostasin using short interfering RNA targeting of prostasin mRNA's 3'
      untranslated region. This drops ENaC currents to 26 +/- 9% of baseline. These
      data predict that prostasin is a major regulator of ENaC-mediated Na+ current in
      DeltaF508 cystic fibrosis epithelia and suggest that airway prostasin is a target
      for therapeutic inhibition to normalize ion current in cystic fibrosis airway.

PMID- 15246976
TI  - CFTR involvement in nasal potential differences in mice and pigs studied using a
      thiazolidinone CFTR inhibitor.
AB  - Nasal potential difference (PD) measurements have been used to demonstrate
      defective CFTR function in cystic fibrosis (CF) and to evaluate potential CF
      therapies. We used the selective thiazolidinone CFTR inhibitor CFTR(inh)-172 to
      define the involvement of CFTR in nasal PD changes in mice and pigs. In normal
      mice infused intranasally with a physiological saline solution containing
      amiloride, nasal PD was -4.7 +/- 0.7 mV, hyperpolarizing by 15 +/- 1 mV after a
      low-Cl- solution, and a further 3.9 +/- 0.5 mV after forskolin. CFTR(inh)-172
      produced 1.1 +/- 0.9- and 4.3 +/- 0.7-mV depolarizations when added after low Cl-
      and forskolin, respectively. Systemically administered CFTR(inh)-172 reduced the
      forskolin-induced hyperpolarization from 4.7 +/- 0.4 to 0.9 +/- 0.1 mV but did
      not reduce the low Cl(-)-induced hyperpolarization. Nasal PD was -12 +/- 1 mV in
      CF mice after amiloride, changing by <0.5 mV after low Cl- or forskolin. In pigs,
      nasal PD was -14 +/- 3 mV after amiloride, hyperpolarizing by 13 +/- 2 mV after
      low Cl- and a further 9 +/- 1 mV after forskolin. CFTR(inh)-172 and glibenclamide
      did not affect nasal PD in pigs. Our results suggest that cAMP-dependent nasal
      PDs in mice primarily involve CFTR-mediated Cl- conductance, whereas cAMP
      independent PDs are produced by a different, but CFTR-dependent, Cl- channel. In
      pigs, CFTR may not be responsible for Cl- channel-dependent nasal PDs. These
      results have important implications for interpreting nasal PDs in terms of CFTR
      function in animal models of CFTR activation and inhibition.

PMID- 15246977
TI  - Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung
      infection in mice.
AB  - Patients with cystic fibrosis have a lesion in the cystic fibrosis transmembrane
      conductance regulator gene (CFTR), which is associated with abnormal regulation
      of other ion channels, abnormal glycosylation of secreted and cell surface
      molecules, and vulnerability to bacterial infection and inflammation in the lung
      usually leading to the death of these patients. The exact mechanism(s) by which
      mutation in CFTR leads to lung infection and inflammation is not clear. Mice
      bearing different mutations in the murine homolog to CFTR (Cftr) (R117H, S489X,
      Y122X, and DeltaF508, all backcrossed to the C57BL/6J background) were compared
      with respect to growth and in their ability to respond to lung infection elicited
      with Pseudomonas aeruginosa-laden agarose beads. Body weights of mice bearing
      mutations in Cftr were significantly smaller than wild-type mice at most ages.
      The inflammatory responses to P. aeruginosa-laden agarose beads were comparable
      in mice of all four Cftr mutant genotypes with respect to absolute and relative
      cell counts in bronchoalveolar lavage fluid, and cytokine levels (TNF-alpha, IL
      1beta, IL-6, macrophage inflammatory protein-2, and keratinocyte chemoattractant)
      and eicosanoid levels (PGE2 and LTB4) in epithelial lining fluid: the few small
      differences observed occurred only between cystic fibrosis mice bearing the S489X
      mutation and those bearing the knockout mutation Y122X. Thus we cannot implicate
      either misprocessing of CFTR or failure of CFTR to reach the plasma membrane in
      the genesis of the excess inflammatory response of CF mice. Therefore, it appears
      that any functional defect in CFTR produces comparable inflammatory responses to
      lung infections with P. aeruginosa.

PMID- 15246978
TI  - The impact of aging and habitual physical activity on static respiratory work at
      rest and during exercise.
AB  - We investigated the effects of aging on the elastic properties of lung tissue and
      the chest wall, simultaneously quantifying the contribution of each component to
      static inspiratory muscle work in resting and exercising adults. We further
      evaluated the interaction of aging and habitual physical activity on respiratory
      mechanics. Static lung volumes and elastic properties of the lung and chest wall
      (pressure-volume relaxation maneuvers) in 29 chronically sedentary and 29
      habitually active subjects, grouped by age, were investigated: young (Y, 20-30
      years), middle-aged (M, 40-50 years), and older (O, >60 years). Using static
      pressure-volume data, we computed the elastic work of breathing (joules per
      liter, J.l(-1)), including inspiratory muscle work, over resting and exercising
      tidal volume excursions. Elastic work of the lung (Y = 0.79 +/- 0.05; M = 0.47 +/
      0.05; O = 0.43 +/- 0.05 J.l(-1)) and chest wall (Y = -0.49 +/- 0.06; M = -0.12
      +/- 0.07; O = 0.04 +/- 0.05 J.l(-1) ) changed significantly with age (P < 0.05).
      With aging, a parallel displacement of the chest wall pressure-volume curve
      resulted in a shift from energy being stored primarily during expiration to
      energy storage during inspiration, and driving expiration, both at rest and
      during exercise. Although deviating significantly from young adults, this did not
      significantly elevate static inspiratory muscle work but resulted in a
      redistribution of the tissues on which this work was performed and the phase of
      the respiratory cycle in which it occurred. Nevertheless, static inspiratory
      muscle work remained similar across age groups, at rest and during exercise, and
      habitual physical activity failed to influence these changes.

PMID- 15246980
TI  - Biological significance of nitric oxide-mediated protein modifications.
AB  - Nitric oxide (NO), despite an apparently simple diatomic structure, has a wide
      variety of functions in both physiology and pathology and within every major
      organ system. It has become an increasingly important scientific challenge to
      decipher how this wide range of activity is achieved. To this end a number of
      investigators have begun to explore how NO-mediated posttranslational
      modifications of proteins may represent mechanisms of cellular signaling. These
      modifications include: 1). binding to metal centers; 2). nitrosylation of thiol
      and amine groups; 3). nitration of tyrosine, tryptophan, amine, carboxylic acid,
      and phenylalanine groups; and 4). oxidation of thiols (both cysteine and
      methionine residues) and tyrosine. However, two particular modifications have
      recently received much attention, nitrosylation of thiols to produce S
      nitrosothiol and nitration of tyrosine residues to produce nitrotyrosine. It is
      the purpose of this review to examine the possibility that these modifications
      may play a role in NO-mediated signaling.

PMID- 15246981
TI  - A possible role for TRPV4 receptors in asthma.

PMID- 15246982
TI  - Accessory cell function of airway epithelial cells.
AB  - Accessory cell function of airway epithelial cells. We previously demonstrated
      that airway epithelial cells (AECs) have many features of accessory cells,
      including expression of class II molecules CD80 and CD86 and functional Fcgamma
      receptors. We have extended these studies to show that freshly isolated AECs have
      mRNA for cathepsins S, V, and H [proteases important in antigen (Ag)
      presentation], invariant chain, human leukocyte antigen (HLA)-DM-alpha and HLA-DM
      beta, and CLIP, an invariant chain breakdown product. A physiologically relevant
      Ag, ragweed, was colocalized with HLA-DR in AECs, and its uptake was increased by
      granulocyte-macrophage colony-stimulating factor and IFN-gamma treatments, which
      had no effect on CD80 and CD86 expression. We demonstrate the presence of other
      costimulatory molecules, including B7h and B7-H1, on AECs and the increased
      expression of B7-H1 on AECs after treatment with granulocyte-macrophage colony
      stimulating factor and IFN-gamma. Finally, we compared T cell proliferation after
      allostimulation with AECs and dendritic cells (DCs). The precursor frequency of
      peripheral blood T cells responding to AECs was 0.264% compared with 0.55% for
      DCs. DCs stimulated CD45RO(+), CD45RA(+), CCR7(+) and CCR7(-)CD4(+), and CD8(+) T
      cells, whereas AECs stimulated only CD45RO(+), CD45RA(-), CCR7(-), CD4(+), and
      CD8(+) T cells. There was no difference in cytokine production, type of memory T
      cells stimulated (effector vs. long-term memory), or apoptosis by T cells
      cocultured with AECs and DCs. The localization of AECs exposed to the external
      environment may make them important in the regulation of local immune responses.

PMID- 15246983
TI  - Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as
      protective adaptations to Alzheimer disease.
AB  - Ever since their initial description over a century ago, senile plaques and their
      major protein component, amyloid-beta, have been considered key contributors to
      the pathogenesis of Alzheimer disease. However, counter to the popular view that
      amyloid-beta represents an initiator of disease pathogenesis, we herein challenge
      dogma and propose that amyloid-beta occurs secondary to neuronal stress and,
      rather than causing cell death, functions as a protective adaptation to the
      disease. By analogy, individuals suffering from altitude sickness nearly always
      have elevated levels of hemoglobin. However, while hemoglobin is toxic to cells
      in culture and increased erythropoiesis at sea level can be deadly, it is clear
      that the increases in hemoglobin occurring at altitude are beneficial. Amyloid,
      like hemoglobin, may also be beneficial, in this case, following neuronal stress
      or disease. Although controversial, a protective function for amyloid-beta is
      supported by all of the available literature to date and also explains why many
      aged individuals, despite the presence of high numbers of senile plaques, show
      little or no cognitive decline. With this in mind, we suspect that current
      therapeutic efforts targeted toward lowering amyloid-beta production or removal
      of deposited amyloid-beta will only serve to exacerbate the disease process.

PMID- 15246984
TI  - Combining growth factors, stem cells, and gene therapy for the aging brain.
AB  - Stem cells have been suggested as a possible "fountain of youth" for replacing
      tissues lost during aging. In the brain, replacing lost neurons is a challenge,
      as they have to then be reconnected with their appropriate targets. Perhaps a
      more realistic and practical strategy for affecting the aging process would be to
      prevent the loss of neurons from occurring, thus retaining intact circuitry.
      Glial cell line-derived neurotrophic factor (GDNF) can reverse some aspects of
      aging in the monkey. Additionally, we have recently shown that GDNF directly
      infused into the human brain has significant effects on the symptoms of Parkinson
      disease. Human neural stem cells can be cultured, genetically modified, and
      transplanted. As such, these cells are ideal for ex vivo gene therapy, and may be
      used in the future as "minipumps" to release GDNF in vivo to protect aging
      neurons. Using such an approach could delay the effects of aging in the brain,
      giving a better quality of life. Stem cells might not be the fountain of youth,
      but provide a fountain of youth through the release of growth factors such as
      GDNF.

PMID- 15246985
TI  - The role of viruses and of APOE in dementia.
AB  - The virus, herpes simplex virus type 1 (HSV1), when present in brain, acts
      together with the type 4 allele of the APOE gene, a known susceptibility factor
      in Alzheimer disease (AD), to confer a strong risk of AD; in carriers of the
      other two main alleles of the gene, the virus does not confer a risk. It also has
      been shown that the outcome of infection in the case of five diseases known to be
      caused by viruses is determined by APOE. It is hoped that the discovery of the
      involvement of HSV1 in AD will lead to future antiviral therapy and possibly to
      immunization against the virus in infancy.

PMID- 15246986
TI  - Metabolic substrates of neuronal aging.
AB  - One mechanism proposed to explain age-dependent changes has been the "Ca(2+)
      hypothesis" of aging. Data indicate that most changes in the Ca(2+) homeostasis
      of the cerebellar granule neurons appear only when the aged neurons are exposed
      to higher levels of stimulation and that these changes are secondary to metabolic
      limitations imposed by altered mitochondrial function.

PMID- 15246987
TI  - The biphasic relationship between regional brain senile plaque and
      neurofibrillary tangle distributions: modification by age, sex, and APOE
      polymorphism.
AB  - Epidemiologic studies indicate that elderly women are at higher risk for
      Alzheimer disease compared to men. In order to pathologically verify this result,
      the extent of AD brain lesions (NFT and SP) was compared for men and women at
      each age, that is, at each decade from 25 years to 95 years, in a large sample of
      > 5000 routine autopsy cases. Women had more affected brain regions beginning in
      late middle age. They also had more extensive SP depositions throughout the brain
      compared to men at each early NFT stage I, II, and III. At later NFT stages IV,
      V, and VI both men and women had extensive SP deposits. The gender gap in SPs at
      early NFT stages was large and specific to women who carried the APOE4 allele (P
      <.001) and in addition to the acceleration in NFT stage also found for APOE4+
      women.

PMID- 15246988
TI  - Decay of mitochondrial metabolic competence in the aging cerebellum.
AB  - Cytochemically evidenced cytochrome oxidase activity was morphometrically
      measured in the cerebellar cortex of adult and old rats. The ratio (R) between
      the area of the precipitate due to the cytochemical reaction and the overall area
      of each mitochondrion was calculated. While in adult rats an inverse correlation
      between mitochondrial size and R values (r = -.905) was envisaged, in old animals
      increasing values of R were paired by increases in mitochondrial area (r =.561).
      Paired-quartile comparisons of the R values from adult and old animals documented
      a marked age-related impairment of the mitochondrial metabolic competence in
      small (I quartile: -31.6%) and medium-sized (II quartile: -26.4; III quartile: 
      16.4) mitochondria, while large organelles showed the lowest age-related decrease
      (IV quartile: -3.0%). The present findings support that a marked dysfunction of
      small and medium-sized mitochondria contributes to the significant decay of
      energy metabolism currently reported in physiological aging.

PMID- 15246989
TI  - Cytochrome oxidase activity in hippocampal synaptic mitochondria during aging: a
      quantitative cytochemical investigation.
AB  - Synaptic mitochondria, cytochemically positive to cytochrome oxidase (COX)
      activity, were investigated by morphometric methods in the hippocampal dentate
      gyrus of adult and old rats. The number of mitochondria/microm(3) of tissue (Nv),
      the volume fraction occupied by mitochondria/microm(3) of tissue (Vv), the
      average mitochondrial volume (V), the longer mitochondrial diameter (F(max)), and
      the ratio R:mitochondrial area/overall area of the cytochemical precipitate due
      to COX activity were measured on COX-positive organelles. In old animals, Nv, Vv,
      V, and F(max) increased at a not significant extent; R was not significantly
      decreased. The complement (%) of longer organelles was higher in old animals. COX
      activity is currently considered an endogenous marker of neuronal oxidative
      metabolism; thus, although our findings refer to the discrete subpopulation of
      COX-positive organelles located at synaptic terminals, they support that changes
      of mitochondrial ultrastructure and metabolic competence may contribute to the
      age-related alterations of neuronal performances.

PMID- 15246990
TI  - Vitamin E deficiency and aging effect on expression levels of GAP-43 and MAP-2 in
      selected areas of the brain.
AB  - The expression levels of GAP-43 and MAP-2, two proteins involved, respectively,
      in axonal and dendritic remodeling, in control adult (11 months), old (24
      months), and vitamin E-deficient (11 months) rats were evaluated. mRNA levels
      were determined by means of a quantitative in situ hybridization procedure in
      subregions of hippocampus and cerebellum. Though a general trend can be observed
      indicating a reduction in GAP-43 expression in aging as compared to adult animals
      and an increase in vitamin E-deprived rats in comparison with adult animals, no
      statistically significant change was found in any region analyzed. In the same
      way, MAP-2 mRNA levels show an increase in vitamin E-deprived rats in comparison
      with other groups tested; only one variation was statistically significant,
      namely the increase in cerebellar cortex MAP-2 nRNA levels in vitamin E-deficient
      versus adult rats. These results suggest that oxidative stress and aging
      negatively affect neuroplasticity, showing different characteristics at the
      dendritic and axonal levels.

PMID- 15246991
TI  - Chronic treatment with a precursor of cellular phosphatidylcholine ameliorates
      morphological and behavioral effects of aging in the mouse [correction of rat]
      hippocampus.
AB  - Normal aging is commonly associated with a decline in memory, mainly for that
      related with newly acquired information. The hippocampal formation (HF) is a
      brain region that has been implicated in this dysfunction. Within the HF there
      are several cellular types, such as pyramidal cells, granule neurons of the
      dentate gyrus, and astrocytes. CDP-choline is a well-known intermediate in the
      biosynthesis of phosphatidylcholine, a phospholipid essential for neuronal
      membrane preservation and function; thus, this compound would attenuate the
      process of neuronal aging. To test this, three groups of male mice were used in
      this study. An adult 12-month-old group (ACG), a 24-month-old (OCG), and an old
      experimental group (OEG) were administered orally a solution of CDP-choline (150
      mg/kg per day) from 12 up to 24 months. Experimental observations suggest that
      CDP-choline has a positive effect on memory (reference errors were attenuated),
      and hippocampal morphology resembled that of younger animals.

PMID- 15246993
TI  - Motor and cognitive recovery induced by bone marrow stem cells grafted to
      striatum and hippocampus of impaired aged rats: functional and therapeutic
      considerations.
AB  - Impairments in motor coordination and cognition in normal and pathological aging
      are often accompanied by structural changes, that is, loss of synapses and
      neurons. Also, it has been shown recently that bone marrow stem cells can give
      origin to cells of different tissues, including neural cells. Given the
      therapeutic implications of increasing health and functional possibilities in the
      aged brain, we have tested the effects of rat femur bone marrow stem cells
      (rBMSCs) grafting to the striatum hippocampus of aged rats with motor or
      cognitive deficits, respectively. Bone marrow cells were transduced with an
      adenovirus driving the expression of green fluorescence protein (GFP) and other
      classic stains to determine their migration, engraftment, differentiation, and
      associated behavioral recovery. Five weeks after it, control and grafted rats
      were re-evaluated with the Morris Water Maze test, Passive avoidance, open-field,
      motor coordination, and Marshall tests and perfused. Brains were processed and
      analyzed for fluorescent protein expression. GFP was detected in cells with some
      differentiation degree into neural-like cells. Their exact phenotype is yet to be
      determined. A significant functional recovery was observed 6 weeks after
      grafting, suggesting a trophic interaction between rBMSCs and the aged/dystrophic
      host brain, or with the host brain progenitor cells and/or by increasing the
      number of functional cells at striatum or hippocampus, suggesting that the aging
      brain keeps its functional plasticity as well as that BMSCs are interesting
      candidates for cell replacement therapies in neurodegenerative disorders.

PMID- 15246992
TI  - Chronic aluminum administration to old rats results in increased levels of brain
      metal ions and enlarged hippocampal mossy fibers.
AB  - The effect of chronic aluminium administration (2 g/L/6 months) was investigated
      in the central nervous system (CNS) of old rats. The content of Al(3+), Cu(2+),
      Zn(2+), and Mn(2+) was measured in prosencephalon + mesencephalon, pons-medulla,
      and cerebellum. The area occupied by the mossy fibers in the hippocampal CA3 zone
      was also measured. In Al-treated rats the contents of Al(3+), Cu(2+), Zn(2+), and
      Mn(2+) were significantly increased in prosencephalon + mesencephalon and pons
      medulla, while no change was observed in the cerebellum except a Cu(2+) decrease.
      The area occupied by the mossy fibers in the CA3 field was significantly
      increased (+32%) in Al-treated rats. Taken together, the present findings
      document that the aging CNS is particularly susceptible to aluminum toxic effects
      that may be responsible for a consistent rise in the cell load of oxidative
      stress. This may contribute, as an aggravating factor, to the development of
      neurodegenerative events, as observed in Alzheimer disease.

PMID- 15246994
TI  - Environmental enrichment-behavior-oxidative stress interactions in the aged rat:
      issues for a therapeutic approach in human aging.
AB  - The effects of environment enrichment on motor activity, exploration, and
      cognitive performances were studied in aged rats. Both nonimpaired (NI) and
      impaired (I) rats were submitted to daily training in a complex-enriched
      environment (cEE) for 60 days. Animals were examined at spatial water maze task,
      passive avoidance test, open-field test, and sensorimotor coordination tasks
      (bridges test and Marshall scales). At the end of experiments, animals were
      killed for brain biochemical determinations (gluthatione content and specific
      ChAT activity). Results after the first evaluation (before training) corroborate
      that the aged rat population showed a heterogeneity in behavioral patterns like
      that observed in humans. Also, cEE modified exploration activity, cognition,
      motor functions, and biochemical markers in both NI and I groups, but changes
      reached significant relevance for the last group. It is significant that
      neurotrophins, "novo" synthesis of neurotransmitters, and oxidative stress levels
      may mediate the observed changes, indicating that the aged brain still has
      appreciable plasticity in response to well-manipulated environmental stimulation.
      Finally, our results also support the novel concepts and programs in
      prevention/reduction both in incidence/severity and outcome of age-associated
      neurodegenerative conditions.

PMID- 15246995
TI  - Digital transcriptome analysis in the aging cerebellum.
AB  - Serial analysis of gene expression (SAGE) was used to identify and quantify all
      expressed cerebellar genes in the adult (P92) and aged (P810) C57BL/6J mouse
      cerebellum. A "closest-neighbor" algorithm was used to differentiate low
      abundance tags from possible sequencing errors in both libraries. Unique tags
      were categorized into four groups: (1) novel genes; (2) ESTs; (3) RIKEN, KIA, and
      hypothetical genes; and (4) known genes. Known genes were further subdivided into
      functional categories based on the gene ontology classification, using a web
      based program developed in this laboratory (MmSAGEClass). Comparison of adult and
      aged cerebellar libraries revealed several genes that were differentially
      expressed, including growth hormone and prolactin, both of which were markedly
      decreased in the aged cerebellum. In addition, several tags showing differential
      expression were not identified in the Unigene database and are likely to
      represent novel genes. The present SAGE data on the aged cerebellar transcriptome
      may reveal candidate genes involved in the aging process.

PMID- 15246996
TI  - Antiaging treatments have been legally prescribed for approximately thirty years.
AB  - There is an interesting divergence between the achievements of geriatrics and
      gerontology. On the one hand, during the last 30 years physicians in many
      developed countries have successfully prescribed several medicines to cure
      various symptoms of senescence. On the other hand, the influence of such
      medicines on human life span practically has not been studied. The most common of
      the relevant medicines are nootropic piracetam, gamma-aminobutyric acid (GABA),
      selegiline, Ginkgo biloba, pentoxifylline, cerebrolysin, solcoseryl, ergoloid,
      vinpocetin, sertraline, and estrogens, among others. Available data from human
      clinical practices and experimental animal studies indicate that treatments with
      these drugs improve learning, memory, brain metabolism, and capacity. Some of
      these drugs increase tolerance to various stresses such as oxygen deficit and
      exercise, stimulate the regeneration of neurons in the old brain, and speed up
      the performance of mental and physical tasks. This means that modern medicine
      already has "antiaging" treatments at its disposal. However, the influence of
      such treatments on the mean and maximal life span of humans, and on the age
      trajectory of a human survival curve has been poorly studied. The increase in
      human life expectancy at birth in the second half of the last century was mostly
      caused by the better survival at the old and oldest old rather than at the young
      ages. In parallel, the consumption of brain protective and regenerative drugs has
      been expanding in the elderly population. We provide evidence in support of the
      idea that the consumption of medicines exerting antiaging properties may
      contribute to the increase in human longevity.

PMID- 15246997
TI  - Aging of cardiac myocytes in culture: oxidative stress, lipofuscin accumulation,
      and mitochondrial turnover.
AB  - Oxidative stress is believed to be an important contributor to aging, mainly
      affecting long-lived postmitotic cells such as cardiac myocytes and neurons.
      Aging cells accumulate functionally effete, often mutant and enlarged
      mitochondria, as well as an intralysosomal undegradable pigment, lipofuscin. To
      provide better insight into the role of oxidative stress, mitochondrial damage,
      and lipofuscinogenesis in postmitotic aging, we studied the relationship between
      these parameters in cultured neonatal rat cardiac myocytes. It was found that the
      content of lipofuscin, which varied drastically between cells, positively
      correlated with mitochondrial damage (evaluated by decreased innermembrane
      potential), as well as with the production of reactive oxygen species. These
      results suggest that both lipofuscin accumulation and mitochondrial damage have
      common underlying mechanisms, likely including imperfect autophagy and ensuing
      lysosomal degradation of oxidatively damaged mitochondria and other organelles.
      Increased size of mitochondria (possibly resulting from impaired fission due to
      oxidative damage to mitochondrial DNA, membranes, and proteins) also may
      interfere with mitochondrial turnover, leading to the appearance of so-called
      "giant" mitochondria. This assumption is based on our observation that
      pharmacological inhibition of autophagy with 3-methyladenine induced only
      moderate accumulation of large (senescent-like) mitochondria but drastically
      increased numbers of small, apparently normal mitochondria, reflecting their
      rapid turnover and suggesting that enlarged mitochondria are poorly
      autophagocytosed. Overall, our findings emphasize the importance of mitochondrial
      turnover in postmitotic aging and provide further support for the mitochondrial
      lysosomal axis theory of aging.

PMID- 15246998
TI  - Response of the senescent heart to stress: clinical therapeutic strategies and
      quest for mitochondrial predictors of biological age.
AB  - The aging heart has an impaired response to many kinds of stress. In clinical
      practice, there is a need for senescence-specific therapies to protect against
      stress and for biochemical markers of senescence to identify those patients most
      in need of therapy. In isolated rat hearts, in human tissues, and in a clinical
      trial, we have shown previously that coenzyme Q(10) has the ability to protect
      the heart against stress especially in senescence. We recently have devised a
      regimen of therapy to protect the senescent heart against stress, combining
      metabolic therapy (coenzyme Q(10), alpha lipoic acid, magnesium orotate, and
      omega 3 polyunsaturated fatty acids) with physical exercise and mental stress
      reduction. The preliminary results of this program are promising. In an endeavor
      to predict the likely response of individual senescent hearts to stress, we
      correlated the tissue load of mitochondrial DNA deletions and total cellular
      mitochondrial DNA copy number in human cardiac tissue with recovery of the same
      tissue from ischemia/reperfusion stress. We found that these mitochondrial
      markers actually were less predictive of impaired response to stress than age
      alone. We conclude that the aging heart has a diminished capacity to recover from
      stress that is not readily predictable by cardiac content of intact mitochondrial
      DNA and that this recovery can be improved by metabolic therapy combined with
      physical exercise and mental stress reduction.

PMID- 15246999
TI  - Impairment of the transcriptional responses to oxidative stress in the heart of
      aged C57BL/6 mice.
AB  - To investigate the transcriptional response to oxidative stress in the heart and
      how it changes with age, we examined the cardiac gene expression profiles of
      young (5 months old), middle-aged (15 months old), and old (25 months old)
      C57BL/6 mice treated with a single intraperitoneal injection of paraquat (50
      mg/kg). Mice were killed at 0, 1, 3, 5, and 7 hours after paraquat treatment, and
      the gene expression profile was obtained with high-density oligonucleotide
      microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the
      young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the
      old mice displayed a significant change in mRNA levels (ANOVA, P <.01). Among
      these, a total of 55 transcripts were determined to be paraquat responsive for
      all age groups. Genes commonly induced in all age groups include those associated
      with stress, inflammatory, immune, and growth factor responses. Interestingly,
      only young mice displayed a significant increase in expression of all three
      isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of
      immediate early genes found to be induced by paraquat was considerably higher in
      the younger animals. These results demonstrate that, at the transcriptional
      level, there is an age-related impairment of specific inducible pathways in the
      response to oxidative stress in the mouse heart.

PMID- 15247000
TI  - Effects of age and caloric restriction on brain neuronal cell death/survival.
AB  - Aging may pose a challenge to the central nervous system, increasing its
      susceptibility to apoptotic events. Recent findings indicate that caloric
      restriction (CR) may have a profound effect on brain function and vulnerability
      to injury and diseases, by enhancing neuroprotection, stimulating the production
      of new neurons, and increasing synaptic plasticity. Apoptosis and apoptotic
      regulatory proteins in the brain frontal cortex of 6-month-old ad libitum fed
      (6AD), 26-month-old ad libitum fed (26AD), and 26-month-old caloric-restricted
      (26CR) male Fischer 344 rats (40% restriction compared to ad libitum fed) were
      investigated. Levels of Poly-ADP ribose polymerase (PARP-DNA repair enzyme; its
      cleaved 89 kDA fragment is a marker of apoptosis), cytoplasmic histone-associated
      DNA fragments, and X chromosome-linked inhibitor of apoptosis (XIAP--an
      endogenous apoptosis inhibitor) were determined. A significant age-associated
      increase in PARP was found, which was ameliorated in the frontal cortices of the
      CR rats. No significant differences in cytoplasmic histone-associated DNA
      fragments with age or with CR were observed. XIAP levels significantly increased
      with age in the brains of the ad libitum animals, while CR animals exhibited the
      highest levels of this inhibitor compared to all groups. Our findings suggest
      that caloric restriction may provide neuroprotection to the aging brain by
      preserving DNA repair enzymes in their intact form, and/or upregulating specific
      antiapoptotic proteins involved in neuronal cell death.

PMID- 15247001
TI  - Acute coronary syndrome, comorbidity, and mortality in geriatric patients.
AB  - Morbidity and mortality rates from heart diseases are highly represented in
      geriatric-aged patients, but these patients also have supporting diseases. Acute
      coronary syndrome includes unstable angina and acute myocardial infarction with
      and without ST elevation. The aim of this study was to make a retrospective
      morbidity analysis of patients admitted to the emergency department. The study is
      made for a period of three years (from 1998 to 2000). It includes 588 patients
      divided by age (395 were 65-75 years old; 193 were older than 75 years) and sex
      (there were 326 men and 262 women). Comorbidity and mortality were investigated.
      Patients with one, two, three, and more than three supporting diseases were
      6.29%, 23.13%, 68.53%, and 2.04%, respectively, of the total number. The most
      frequent geriatric patients had heart failure, followed by endocrinological
      diseases (type 2 diabetes, obesity, struma), neurological diseases (insultus,
      paresis), and chronic kidney diseases (pielonephritis, nephrolithiasis). The
      combination of hypertension, heart failure, and type 2 diabetes had the highest
      comorbidity frequency. The mortality rate for 1998 was 8.81%, for 1999 7.74%, and
      for 2000 13.41%. The mortality rate at the first 12 hours at the beginning of the
      acute coronary syndrome was 66.6%. Geriatric patients suffer from many diseases,
      and at the beginning of the onset of acute coronary syndrome they have
      multiorganal failure. Elderly patients are a high-risk contingent in intensive
      coronary care units.

PMID- 15247002
TI  - Differential regulation of telomerase in endothelial cells by fibroblast growth
      factor-2 and vascular endothelial growth factor-a: association with replicative
      life span.
AB  - In cultured human umbilical vein endothelial cells (HUVECs), fibroblast growth
      factor-2 (FGF-2), but not vascular endothelial growth factor-A (VEGF-A),
      upregulates telomerase activity. Here, we examined the functional significance of
      this differential regulation on the replicative life span of HUVECs. HUVECs were
      serially passaged until senescence under four different conditions: (1) EGM-2, a
      medium containing both VEGF-A and FGF-2; (2) basal medium (BM), consisting of EGM
      2 devoid of FGF-2 and VEGF-A; (3) BM supplemented with FGF-2; and (4) BM
      supplemented with VEGF-A. Cells cultured in BM demonstrated decreased growth rate
      and ceased to proliferate at approximately 15 population doublings (PDs), whereas
      those cultured with VEGF-A alone initially proliferated vigorously but arrested
      growth abruptly at a PD level comparable with cultures grown in BM. In contrast,
      cells maintained in EGM-2 or in BM/FGF-2 attained a normal replicative life span
      (approximately 40 PDs). These differences in replicative behavior were reflected
      by the early appearance of a senescent phenotype in cultures grown in BM or
      BM/VEGF-A. HUVECs grown in the presence of VEGF-A alone have a decreased life
      span compared with cultures maintained with FGF-2. This suggests that the
      upregulation of telomerase activity by FGF-2, an effect not achieved with VEGF-A,
      plays a functional role in preventing the early onset of senescence.

PMID- 15247003
TI  - Interleukin-7: an interleukin for rejuvenating the immune system.
AB  - Infection of an individual (aged 20-30 years) by a virus will cause a response
      from the T (thymus derived) lymphocytes of which there are approximately 3 x
      10(11). If the individual has not met the virus before, the response will come
      from the naive T cell subset (50 +/- 10% of the total T cell pool at this age)
      containing recent thymic emigrants produced from the thymus at approximately
      10(8) per day. Their antigen-specific receptor has a defined specificity governed
      by the conformation of its two chains (alpha and beta), and the repertoire of
      specificities is somewhere in the region of 2 x 10(7) to 10(8). A successful
      response leads to clonal expansion and the generation of memory T cells to the
      infecting agent.

PMID- 15247004
TI  - T cell replicative senescence: pleiotropic effects on human aging.
AB  - Long-term culture studies using CD8 T cells, the immune cells responsible for
      control of viral infection, have identified the major features of replicative
      senescence. Aging is associated with increased proportions of CD8 T cells with
      similar characteristics, such as absence of expression of the CD28 costimulatory
      molecule and reduced antiviral effector functions. Proinflammatory cytokines
      produced by senescent CD8 T cells also may exert pleiotropic suppressive effects
      on overall immune function and bone homeostasis. Thus, modulation of T cell
      replicative senescence may provide a comprehensive therapeutic strategy to
      prevent multiple age-associated pathologies.

PMID- 15247005
TI  - Zinc, immune plasticity, aging, and successful aging: role of metallothionein.
AB  - The capacity of the remodeling immune responses during stress (immune plasticity)
      is fundamental to reach successful aging. We herein report two pivotal models to
      demonstrate the relevance of the immune plasticity in aging and successful aging.
      One model is represented by the circadian rhythms of immune responses; the other
      one is the immune responses during partial hepatectomy/liver regeneration (pHx).
      The latter is suggestive because it mimics the immunosenescence and chronic
      inflammation 48 hours after partial hepatectomy in the young through the
      continuous production of IL-6, which is the main cause of immune plasticity lack
      in aging. The constant production of IL-6 leads to abnormal increments of zinc
      bound metallothionein (MT), which is, in turn, unable in zinc release in aging.
      As a consequence, low zinc ion bioavailability appears for thymic and extrathymic
      immune efficiency, in particular, of liver NKT cells bearing TCR gd. The
      remodeling during the circadian cycle and during pHx of zinc-bound MT confers the
      immune plasticity of liver NKT gamma delta cells and NK cells in young and very
      old age, not in old age. Therefore, zinc-bound MT homeostasis is crucial in
      conferring liver immune plasticity with subsequent successful aging.

PMID- 15247006
TI  - Macrophages of the adrenal cortex: a morphological study of the effects of aging
      and dexamethasone administration.
AB  - Macrophages are present throughout the adrenal cortex, particularly in the deeper
      layers. They locate next to parenchyma cells, which secrete glucocorticoids under
      the regulation of the pituitary adrenocorticotropic hormone (ACTH). Blockade of
      ACTH secretion is followed by adrenocortical cell atrophy and apoptosis, an
      effect likely to cause an increase in local macrophage number and phagocytic
      activity. The purpose of the current study was to verify this effect and
      ascertain its age-related variation after ACTH blockade. Male rats at five
      different ages ranging from 2 to 24 months were divided into two groups, which
      were injected with dexamethasone phosphate or saline for 3 days. The adrenals
      were processed for morphological and morphometric study. The age-related increase
      in macrophage number seen in a survey of the sections was confirmed in the
      quantitative study: a significant increase in volume density (Vv), numerical
      density (Nv), and cell volume was found in both groups; Vv and Nv were higher in
      treated rats. These findings in the deeper layers of the cortex suggest a
      continuous process of phagocytosis, likely of parenchyma dead cells or their
      debris, which increases further after ACTH blockade. An additional modulatory
      effect of macrophages also may occur because of their secretory role.

PMID- 15247007
TI  - Looking for immunological risk genotypes.
AB  - Several functional markers of the immune system may be used either as markers of
      successful aging or conversely as markers of unsuccessful aging. Particularly, a
      combination of high CD8 and low CD4 and poor T cell proliferation has been
      associated with a higher two-year mortality in very old subjects. Therefore,
      genetic determinants of longevity should reside in those polymorphisms for the
      immune system genes that regulate immune responses. Concerning these changes in T
      cell subpopulations, how much they depend on the immunogenetic background and how
      much they depend on individual antigenic load, such as chronic infections, should
      be assessed. As previously demonstrated in our population, the interleukin (IL)-2
      high-producer genotype is less frequent in old men than in young people;
      conversely, the IL-10 high-producer genotype is increased in old men. In this
      study, we tried to assess the role of low- and high-producer genotypes for IL-10
      and IL-2 in the CD4 and CD8 absolute values, taking into account gender and age.
      The results suggest that old men carrying an anti-inflammatory IL-10 high
      producer genotype or a proinflammatory IL-2 low-producer genotype show the lowest
      values of CD8 cells. Although in our study we were not able to show any
      correlation with CD4 values and no functional assessment of T cell was performed,
      these results suggest that cytokine genotypes may be involved in the
      subpopulation dynamics in old age.

PMID- 15247008
TI  - Total deletion of in vivo telomere elongation capacity: an ambitious but possibly
      ultimate cure for all age-related human cancers.
AB  - Despite enormous effort, progress in reducing mortality from cancer remains
      modest. Can a true cancer "cure" ever be developed, given the vast versatility
      that tumors derive from their genomic instability? Here we consider the efficacy,
      feasibility, and safety of a therapy that, unlike any available or in
      development, could never be escaped by spontaneous changes of gene expression:
      the total elimination from the body of all genetic potential for telomere
      elongation, combined with stem cell therapies administered about once a decade to
      maintain proliferative tissues despite this handicap. We term this therapy WILT,
      for whole-body interdiction of lengthening of telomeres. We first argue that a
      whole-body gene-deletion approach, however bizarre it initially seems, is truly
      the only way to overcome the hypermutation that makes tumors so insidious. We
      then identify the key obstacles to developing such a therapy and conclude that,
      while some will probably be insurmountable for at least a decade, none is a clear
      cut showstopper. Hence, given the absence of alternatives with comparable
      anticancer promise, we advocate working toward such a therapy.

PMID- 15247009
TI  - Insights into aging obtained from p53 mutant mouse models.
AB  - Cancer suppression is an integral component of longevity in organisms with
      renewable tissues. A number of genes in the mammalian genome function in cancer
      prevention, and some of these have been directly implicated in longevity
      assurance. One such longevity assurance gene is the tumor suppressor p53, a
      transcription factor that is mutated or dysregulated in most human cancers. Early
      studies have linked p53 to the induction of cellular senescence, whereas recent
      reports implicate it as a potential regulator of organismal aging. We have shown
      by gene inactivation studies that loss of p53 function enhances tumor
      susceptibility and reduces longevity in the mouse. A recent serendipitously
      generated p53 mutant allele resulted in a hypermorphic version of p53 that
      displays increased cancer resistance, yet also mediates decreased longevity. The
      reduced longevity is accompanied by the accelerated onset of a variety of aging
      phenotypes. These include a 20% decrease in median life span, early osteoporosis,
      lordokyphosis, organ atrophy, delayed wound healing, and a reduced regenerative
      response after various stresses. Since the initial characterization of these
      mutant mice, we have attempted to elucidate the underlying molecular and cellular
      mechanisms that could be influencing the early aging phenotypes. Molecular
      studies of the p53 mutant allele product indicate that it induces an increase in
      p53 activity in both in vitro and in vivo contexts. The age-associated loss of
      organ cellularity and reduced tissue regenerative responses in the mutant mice
      are consistent with an accelerated loss of stem cell functional capacity. Our
      model is that enhanced growth inhibitory activity of p53 produces an earlier loss
      of the ability of stem cells to produce adequate numbers of progenitor and mature
      differentiated cells in each organ. Currently, we are performing stem cell
      functional assays from p53 mutant and wild-type mice to test this model. One
      challenge for the future will be to find ways to manipulate p53 function to
      provide increased cancer resistance, yet still enhance overall organismal
      longevity.

PMID- 15247010
TI  - Engineering anticancer T cells for extended functional longevity.
AB  - Like other somatic cells, human T lymphocytes have a finite replicative capacity
      in vitro, and, by implication and consistent with the limited data available, in
      vivo as well. An accumulation of dysfunctional T cells may be detrimental under
      conditions of chronic antigenic stress (chronic infection, cancer, autoimmunity).
      Using T cells from young donors to model the process of T cell clonal expansion
      in vitro under these conditions reveals age-associated increasing levels of
      oxidative DNA damage and microsatellite instability (MSI), coupled with
      decreasing DNA repair capacity, telomerase induction and telomere length,
      decreased levels of expression of the T cell costimulator CD28 and consequently
      reduced secretion of the T cell growth factor interleukin-2 (IL-2). However, data
      from similar experiments using T cell clones (TCCs) derived from extremely
      healthy very elderly donors ("successfully aged") indicate that DNA repair is
      better maintained, MSI less prevalent, and (already short) telomere lengths are
      maintained. Nonetheless, oxidative DNA damage is seen to the same extent, and
      clonal longevity is also similar in these clones. DNA damage levels are reduced
      by culture in 5% oxygen, but longevity is not improved. This may be because of
      the requirement for intermittent reactivation via receptor pathways dependent on
      free radical production in T cells. These recent findings from our international
      immunosenescence research consortium suggest that strategies other than telomere
      maintenance, better protection against free radicals, or improved DNA repair will
      be required for functional longevity extension of human TCCs. To obtain
      sufficient cells for adoptive immunotherapy of cancer, alternative avenues need
      exploration; currently, these include enforced expression of certain heat shock
      proteins and proteasome components, and interference with the expression of
      negative regulatory receptors expressed by T cells.

PMID- 15247012
TI  - The role of cellular senescence may be to prevent proliferation of neighboring
      cells within stem cell niches.
AB  - It has long been suspected that cellular senescence is an anticancer mechanism;
      however, it has been difficult to understand the advantage for the organism of
      retaining mutant cells in a postmitotic state rather than simply deleting them by
      apoptosis. It is proposed that in certain circumstances apoptosis promotes
      neoplasia by causing cells adjacent to the deleted cell to divide and that the
      role of cellular senescence is to prevent this. This may be particularly
      important in mammalian stem cell niches. After loss of a stem cell from a niche,
      another stem cell within the same niche divides symmetrically to restore the
      original number. The most important human malignancies arise from tissues
      maintained by stem cells, and there is increasing evidence that stem cells are
      the targets for at least the initial genetic changes that occur during
      carcinogenesis. If a subset of stem cells within a niche arises containing an
      oncogenic mutation, then tumor suppressor mechanisms promote apoptosis of these
      cells, and the niche restores the original number of stem cells by replication of
      both normal and mutated stem cells. Thus, paradoxically apoptosis increases
      turnover of mutant cells with associated risk of further genetic changes.
      However, if in addition mutant cells can become senescent, then the niche is
      progressively filled by senescent cells until either the mutant cells are
      eliminated or the niche is completely occupied by postmitotic cells, thereby
      preventing further evolution of the neoplastic clone. The consequences of this
      hypothesis are explored by computer modeling.

PMID- 15247011
TI  - Telomerase expression is differentially regulated in birds of differing life
      span.
AB  - Cellular senescence caused by telomere shortening has been suggested as one
      potential causal agent of aging. In some tissues, telomeres are maintained by
      telomerase; however, telomerase promotes tumor formation, suggesting a trade-off
      between aging and cancer. We predicted that telomerase activity should vary
      directly with life span. We determined telomerase activity in bone marrow in
      cross-sectional samples from two short-lived bird species and two long-lived bird
      species. The two short-lived species had high telomerase activity as hatchlings
      but showed a sharp downregulation in both the young and old adults, whereas the
      two long-lived species had relatively high telomerase activity in bone marrow
      that did not decrease with age. In zebra finches, the age-related change in
      telomerase activity varied in different tissues. Telomerase activity increased
      late in life in skeletal muscle, liver, and gonad, but not in blood or bone
      marrow.

PMID- 15247013
TI  - The aging/precancerous gastric mucosa: a pilot nutraceutical trial.
AB  - The aim of this study was to test the effect of antioxidant supplementation on
      enzymatic abnormalities and free radical-modified DNA adducts associated with
      premalignant changes in the gastric mucosa of elderly patients with HP-negative
      atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal
      metaplasia underwent a nutritional interview and a gastroscopy with multiple
      biopsy samples in the antrum that were processed for histology and for assaying:
      alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and
      8-OHdG. Patients were randomly allocated into three matched groups and
      supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two
      tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified
      fermented papaya preparation with basic science-validated
      antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls.
      Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients
      showed a significantly (P <.05) increased level of mucosal MDA and XO
      concentration that were reverted to normal by each supplementation (P <.05). All
      supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded
      the most effective (P < 0.05) and was the only one significantly decreasing 8
      OhdG (P < 0.05). These data suggest that antioxidant supplementation, and,
      namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG
      patients and especially in the elderly population.

PMID- 15247014
TI  - Cancer as "rejuvenescence".
AB  - Comparative analysis of malignant and senescent cells shows that their phenotypic
      features are in many instances contrary. Cancer cells do not "age"; their
      metabolic and growth characteristics are opposite to those observed with cellular
      aging (both replicative and functional). In many such characteristics, cancer
      cells resemble embryonic cells. One can say that cancer manifests itself as a
      local uncontrolled "rejuvenation" in an organism. Available evidence from human
      and animal studies suggests that the opposite phenotypic features of aging and
      cancer arise from the opposite regulation of common genes, such as those
      participating in apoptosis/growth arrest or in growth signal transduction
      pathways in the cell. For instance, in aging cells and organisms, proto-oncogenes
      are often downregulated, while tumor suppressors are permanently expressed. In
      cancer cells the situation is just the opposite: the proto-oncogenes are commonly
      overexpressed, while tumor suppressors are downregulated. This fact may have
      various applications for the development of new antiaging and anticancer
      treatments. First, genes that are oppositely regulated in cancer and aging could
      be candidate targets for antiaging interventions. Their "cancerlike" regulation,
      if strictly controlled, might help to rejuvenate the aging organism. Recent
      evidence from human and animal studies in support of this view is discussed.
      Second, the fact that cancer cells do not "age" implies that these cells may have
      a survival advantage in the surrounding of senescent cells. This could be a
      partial reason for an increase in the risk of cancer with age, because the
      proportion of senescent cells increases in an organism with age, too. In such a
      situation, the rejuvenation of normal cells surrounding the tumor might be a
      perspective anticancer treatment. For instance, a controlled activation of
      oncogenes in normal host cells or the grafting of young proliferating cells (such
      as embryonic stem cells) in the area near a malignant tumor might help to
      supplant cancer cells rather than to kill them.

PMID- 15247015
TI  - Functional analysis of clusterin/apolipoprotein J in cellular death induced by
      severe genotoxic stress.
AB  - Clusterin/apolipoprotein J (CLU) is a secreted heterodimeric glycoprotein that is
      reportedly upregulated during tumorigenesis, as well as during cell injury or
      death. Despite extensive efforts, CLU function during cellular death remains
      largely elusive. We are using as a model system to study CLU function three human
      osteosarcoma (OS) cell lines, namely, Sa OS, KH OS, and U-2 OS cells, induced to
      die after exposure to severe genotoxic stress mediated by the chemotherapeutic
      drug doxorubicin (DXR). We initially applied small interfering RNA (siRNA)
      mediated specific knockdown of the CLU protein in OS cells. In all three cell
      lines, CLU knockdown resulted in increased sensitization to DXR-induced
      apoptosis. Supportively, moderate levels of forced transgene-mediated CLU stable
      overexpression in KH OS cells could rescue them from DXR-mediated apoptosis. In
      contrast, stable overexpression of high CLU levels in Sa OS and U-2 OS cells
      augmented apoptosis induced by cell exposure to severe DXR-mediated genotoxic
      stress. In summary, our data provide evidence that, although CLU is essential for
      cellular homeostasis, it may become highly cytotoxic in certain cellular contexts
      when it accumulates in high amounts intracellularly either by direct synthesis or
      by uptake from the extracellular milieu.

PMID- 15247016
TI  - Evidence of preferential protein targets for age-related modifications in
      peripheral blood lymphocytes.
AB  - Oxidatively modified proteins have been analyzed in aging human peripheral blood
      lymphocytes since protein modification by oxidation and other related pathways
      are believed to contribute to the intracellular age-related accumulation of
      damaged proteins, a process that has been associated with the cellular functional
      deficits that occur with age. Advanced glycation end products (AGE) were
      quantified and the pattern of glycated proteins analyzed by two-dimensional gel
      electrophoresis followed by Western blotting using an anti-AGE antibody raised
      against glycated RNAse. The protein silver stain and the immunoblot patterns were
      not superimposable, indicating that glycoxidative modifications are targeting
      only a restricted set of proteins. Modification of proteins with the lipid
      peroxidation product 4-hydroxy-2-nonenal has also been studied. The patterns of
      modified proteins have been analyzed using two- dimensional gel electrophoresis
      followed by Western blotting with an antibody recognizing 4-hydroxy-2-nonenal
      protein adducts using the same proteomic approach as for glycoxidative
      modifications. Specific protein targets for these modifications, that might serve
      as biomarkers of aging lymphocytes, are currently characterized and identified by
      mass spectrometry.

PMID- 15247017
TI  - Protective effects of mutant ubiquitin in transgenic mice.
AB  - The K48R mutant ubiquitin can exert profound in vivo protective effects against a
      variety of insults, including agents of direct clinical relevance. The
      manipulation of the ubiquitin/proteasome pathway has enormous potential for
      clinical benefit, and it is not unreasonable to expect that such benefits will
      include diseases of aging.

PMID- 15247018
TI  - Algae extract protection effect on oxidized protein level in human stratum
      corneum.
AB  - Modification of proteins by reactive oxygen species is implicated in different
      disorders. The proteasome is a multicatalytic proteinase in charge of
      intracellular protein turnover and of oxidized proteins degradation.
      Consequently, proteasome function is very important in controlling the level of
      altered proteins in eukaryotic cells. Evidence for a decline in proteasome
      activity during skin photo-aging has been provided in Bulteau et al. in 2002. The
      ability of a lipid algae extract (Phaeodactylum tricornutum) to stimulate 20S
      proteasome peptidase activities was described by Nizard et al. in 2001.
      Furthermore, keratinocytes treated with Phaeodactylum tricornutum extract and
      then UVA and UVB irradiated, exhibited a sustained level of proteasome activity
      comparable to the one of nonirradiated cells. The level of modified proteins can
      be quantified by measurement of protein carbonyl content (Oxyblot technique),
      which has been shown to increase with aging and other disorders. In this paper,
      it is described that, in the presence of this lipid algae extract, the level of
      oxidized proteins is reduced, as assessed by the Oxyblot technique. These results
      are obtained both with culture of human keratinocytes and stratum corneum skin
      cells (obtained by stripping) from human volunteers. Altogether, these results
      argue for the presence of compounds in this algae extract that have a stimulating
      and/or protective effect on proteasome activity, resulting in a decreased level
      of protein oxidation.

PMID- 15247019
TI  - Heat shock protein 47 expression in aged normal human fibroblasts: modulation by
      Salix alba extract.
AB  - Heat shock protein (HSP) 47 is a specific chaperone of procollagen. This heat
      shock protein is responsible for the correct three-dimensional organization of
      procollagen and its control-quality prior secretion. The aim of the study is to
      evaluate the level of HSP 47 in aged, photoaged, and senescent fibroblasts and
      its modulation by a plant extract (Salix alba). The level of HSP 47 and/or
      procollagen expression in fibroblasts was measured by real-time RT-PCR (mRNA
      transcripts) and by flow cytometry (immunochemistry technique for measurement of
      arbitrary fluorescence intensity). Immunochemistry techniques and confocal
      microscopy were used to visualize the cellular localization of HSP 47 and
      procollagen. These parameters were compared with different age donors,
      nonsenescent, and senescent fibroblasts. Fibroblasts were irradiated by a
      noncytotoxic dose of UVA (6 J/cm(2)), and HSP 47 level was evaluated. S. alba
      extract was tested for its capacity to modulate HSP 47 expression. Colocalization
      of HSP 47 and procollagen was shown by confocal microscopy, indicating that HSP
      47 could play a role of procollagen molecular chaperone in the cellular model. It
      was also shown that the HSP 47 level is decreased in old-donor cells, senescent,
      and irradiated cells. This decrease can be modulated by a S. alba extract
      (polyphenols rich) in a dose-dependent manner. The evaluation of HSP 47
      expression in the experimental conditions can lead to a new approach of aging and
      photoaging, pointing out the implication of this chaperone in these
      pathophysiologic phenomena. Modulation of HSP 47 expression by this family of
      molecules could be of cosmetic and/or dermatologic interest.

PMID- 15247020
TI  - RAGE: a new pleiotropic antagonistic gene?
AB  - Advanced glycation end products (AGEs) are the result of a nonenzymatic reaction
      of reducing sugars with primary amino groups of proteins (Maillard reaction).
      They accumulate in various tissues in the course of aging. Because AGEs induce
      protein cross-links and oxidative stress (radicals) within cells and tissues,
      they have been implicated in the development of many degenerative diseases.
      Binding of AGEs to receptors like RAGE induces the release of profibrotic
      cytokines, such as TGF-beta or proinflammatory cytokines, such as TNF-alpha or IL
      6. AGE inhibitors or breakers, such as aminoguanidine or ALT-711, inhibit the age
      induced heart hypertrophy or stiffness of the large arteries. On the other hand,
      little is known about the physiological role of RAGE as the receptor of AGEs.
      Investigations about the expression of RAGE in lung tissue and lung tumors may
      give a hint for such a role.

PMID- 15247021
TI  - Genetic correction of mitochondrial diseases: using the natural migration of
      mitochondrial genes to the nucleus in chlorophyte algae as a model system.
AB  - Mitochondrial diseases display great diversity in clinical symptoms and
      biochemical characteristics. Although mtDNA mutations have been identified in
      many patients, there are currently no effective treatments. A number of human
      diseases result from mutations in mtDNA-encoded proteins, a group of proteins
      that are hydrophobic and have multiple membrane-spanning regions. One method that
      has great potential for overcoming the pathogenic consequences of these mutations
      is to place a wild-type copy of the affected gene in the nucleus, and target the
      expressed protein to the mitochondrion to function in place of the defective
      protein. Several respiratory chain subunit genes, which are typically mtDNA
      encoded, are nucleus encoded in the chlorophyte algae Chlamydomonas reinhardtii
      and Polytomella sp. Analysis of these genes has revealed adaptations that
      facilitated their expression from the nucleus. The nucleus-encoded proteins
      exhibited diminished physical constraints for import as compared to their mtDNA
      encoded homologues. The hydrophobicity of the nucleus-encoded proteins is
      diminished in those regions that are not involved in subunit-subunit interactions
      or that contain amino acids critical for enzymatic reactions of the proteins. In
      addition, these proteins have unusually large mitochondrial targeting sequences.
      Information derived from these studies should be applicable toward the
      development of genetic therapies for human diseases resulting from mutations in
      mtDNA-encoded polypeptides.

PMID- 15247022
TI  - Where and when do somatic mtDNA mutations occur?
AB  - It is generally assumed that somatic mtDNA mutations are originally created in
      the cells where these mutations are currently found. Accumulating data indicate,
      however, that cells with a particular mtDNA mutation tend to "cluster," that is,
      occur repeatedly within a given sample, but not in the others. Clusters likely
      are clonal, which implies that mtDNA mutations do not originate in the cells that
      currently carry them, but rather in those cells' progenitors, such as stem or
      satellite cells, or even earlier in the development. Importantly, a majority of
      mtDNA mutations appear to belong to such clusters, and thus mutational events in
      progenitor cells may be one of the major sources of mtDNA mutations in healthy
      aging tissue. More research including the analysis of multiple samples per
      individual is needed to confirm the existence of clustering and to distinguish
      between the possible clustering mechanisms.

PMID- 15247023
TI  - Genomic instability, aging, and cellular senescence.
AB  - Aging can be defined in practical terms as a series of time-related processes
      that ultimately bring life to a close. Genomic instability has been implicated as
      a major causal factor in aging. Here, we describe the use of a transgenic mouse
      model, harboring lacZ reporter genes as part of a plasmid construct integrated at
      one or more chromosomal locations, to study genomic instability during aging of
      different mouse organs and tissues as well as in mouse embryonic fibroblasts
      during primary culture.

PMID- 15247024
TI  - Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET
      technique.
AB  - Werner syndrome (WS) is an inherited genetic disease in which individuals display
      the premature aging of a selected subset of tissues. The disorder results from
      the loss of function mutations in the wrn gene. Wrn codes for a member of the
      RecQ helicase family with a unique nuclease domain. There is significant evidence
      that the role of wrn is to assist in the repair and reinitiation of DNA
      replication forks that have stalled. Loss of the wrn helicase imposes a distinct
      set of phenotypes at the cellular level. These include premature replicative
      senescence (in a subset of cell types), chromosomal instability, a distinct
      mutator phenotype, and hypersensitivity to a limited number of DNA damaging
      agents. Unfortunately, most of these phenotypes are not suitable for the rapid
      assessment of loss of function of the wrn gene product. However, WS cells have
      been reported to show abnormal sensitivity to the drug camptothecin (an inhibitor
      of topoisomerase type I). A rapid assay for this sensitivity would be a useful
      marker of loss of wrn function. The COMET (single-cell gel electrophoresis) assay
      is a rapid, sensitive, versatile, and robust technique for the quantitative
      assessment of DNA damage in eukaryotic cells. Using this assay, we have found
      that a significantly increased level of strand breaks can be demonstrated in WS
      cells treated with camptothecin compared with normal controls.

PMID- 15247025
TI  - Mitochondrial dysfunction is a common phenotype in aging and cancer.
AB  - An interesting clue with regard to molecular mechanisms underlying age-associated
      cancers is the apparent defect in mitochondrial function. Recent studies
      demonstrate a progressive decline in mitochondrial function during aging. Studies
      have established that the decline in mitochondrial function is due to the
      accumulation of mutations in mitochondrial DNA. These observations suggest that
      the mitochondrial dysfunction that accompanies aging may exert a major influence
      on carcinogenesis.

PMID- 15247026
TI  - The extent and significance of telomere loss with age.
AB  - By imposing a limit on the proliferative life span of some human cell types,
      telomere loss and the subsequent onset of replicative senescence have been
      proposed to contribute to age-related disease. Although there is a large body of
      in vitro data to reveal the mechanisms by which telomere erosion triggers
      senescence, technical limitations have hampered our ability to understand the
      full extent of telomere erosion in vivo. Thus far, we have evidence of age
      related telomere loss; however, the lack of resolution of existing technologies
      does not allow us to determine if telomere erosion is extensive enough to trigger
      replicative senescence in vivo. This coupled with the considerable
      interindividual heterogeneity, and the overlap in telomere lengths between young
      and elder individuals, render any correlation weak and the significance unclear.
      However, recent technical developments, including adaptations of quantitative
      telomere fluorescence, in situ hybridization (Q-FISH), and the PCR-based single
      telomere length analysis (STELA), have increased the resolution of telomere
      length analysis. These technologies promise to provide the evidence required to
      address the full extent and significance of telomere loss in the human aging
      process. Here, we review published data on the dynamics of telomere erosion with
      age in the human body.

PMID- 15247027
TI  - Measurement of the 4,834-bp mitochondrial DNA deletion level in aging rat liver
      and brain subjected or not to caloric restriction diet.
AB  - Several studies have demonstrated an age-related accumulation of the amount of a
      specific 4834-bp mitochondrial DNA (mtDNA) deletion in different tissues of rat
      (liver, brain, and skeletal muscle). We investigated the influence of a caloric
      restriction diet (CR) on a selected age-associated marker of mtDNA damage, as the
      4834-bp deletion, using quantitative real-time PCR. The mtDNA deleted level has
      been determined with respect to the mitochondrial D-loop level, using specific
      primers and TaqMan probes for each target. In liver we found an age-related
      increase of the deletion level (twofold) that was reversed and brought back to
      the adult level by a CR diet. On the contrary, in the brain the age-related
      increase of the deletion level (eightfold) was not affected by CR at all. The
      different effect of the CR on the deletion level in liver and brain might be a
      further element supporting the tissue-specificity of the aging process.

PMID- 15247028
TI  - Investigation of the signaling pathways involved in the proliferative life span
      barriers in werner syndrome fibroblasts.
AB  - Werner syndrome (WS) fibroblasts enter replicative senescence after a reduced in
      vitro life span. Although this has been postulated as causal in the accelerated
      aging seen in this disease, controversy remains as to whether WS is showing the
      acceleration of a normal cellular aging mechanism or, instead, the occurrence of
      a novel WS-specific process. To address this, we analyzed the signaling pathways
      involved in senescence in WS fibroblasts. Cultured WS fibroblasts underwent
      senescence after approximately 20 population doublings, with the majority of the
      cells having a 2N DNA content. This was associated with high levels of the CdkIs
      p16 and p21. Senescent WS cells reentered the cell cycle after microinjection of
      a p53-neutralizing antibody. Similarly, presenescent WS fibroblasts expressing
      the E6 and/or E7 oncoproteins bypassed M1 and ultimately reached a second
      proliferative life span barrier, which strongly resembled the second life span
      barriers found in normal cells for growth dynamics, cellular morphology, and
      expression of p16 and p21. The strong similarity between the signaling pathways
      triggering cell cycle arrest in WS and normal fibroblasts provides support for
      the defect in WS causing the acceleration of a normal aging mechanism and
      validates the use of WS as a model for some aspects of human aging.

PMID- 15247029
TI  - Mechanism of telomere shortening by oxidative stress.
AB  - We investigated whether oxidative stress, which contributes to aging, accelerates
      the telomere shortening in human cultured cells. The terminal restriction
      fragment (TRF) from WI-38 fibroblasts irradiated with UVA (365-nm light)
      decreased with increasing of the irradiation dose. Furthermore, UVA irradiation
      dose-dependently increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxodG) in both WI-38 fibroblasts and HL-60 cells. In order to clarify the
      mechanism of the acceleration of telomere shortening, we investigated site
      specific DNA damage induced by UVA irradiation in the presence of endogenous
      photosensitizers using (32)P 5' end-labeled DNA fragments containing telomeric
      oligonucleotide (TTAGGG)(4). UVA irradiation with riboflavin induced 8-oxodG
      formation in the DNA fragments containing telomeric sequence, and Fpg protein
      treatment led to chain cleavages at the central guanine of 5'-GGG-3' in telomere
      sequence. Human 8-oxodG-DNA glycosylase introduces a chain break in a double
      stranded oligonucleotide specifically at an 8-oxodG residue. The amount of 8
      oxodG formation in DNA fragment containing telomere sequence [5'
      CGC(TTAGGG)(7)CGC-3'] was approximately five times more than that in the DNA
      fragment containing nontelomere sequence [5'-CGC(TGTGAG)(7)CGC-3']. Furthermore,
      H(2)O(2) plus Cu(II) caused DNA damage, including 8-oxodG formation, specifically
      at the GGG sequence in the telomere sequence (5'-TTAGGG-3'). It is concluded that
      the formation of 8-oxodG at the GGG triplet in telomere sequence induced by
      oxidative stress could participate in acceleration of telomere shortening.

PMID- 15247030
TI  - Lysosomal redox-active iron is important for oxidative stress-induced DNA damage.
AB  - Data show that specifically chelating lysosomal redox-active iron can prevent
      most H(2)O(2)-induced DNA damage. Lysosomes seem to contain the major pool of
      redox-active labile iron within the cell. Under oxidative stress conditions, this
      iron may then relocate to the nucleus and play an important role for DNA damage
      by taking part in Fenton reactions.

PMID- 15247031
TI  - Low levels of mtDNA deletion mutations in ETS normal fibers from aged rats.
AB  - The objectives were (1) to determine whether deletion mutations occur in
      phenotypically normal type I and type II fibers, (2) to quantify the levels of
      both deletion mutant and wild-type (wt) mtDNA (nondeletion) within single normal
      fibers containing mutant mtDNA, and (3) to quantify the amount of wt mtDNA in
      genotypically and phenotypically normal type I and type II fibers. Deletion
      mutations in normal fibers are not restricted to specific fiber types, although
      clonal accumulation of mtDNA deletion mutations and subsequent ETS abnormalities
      occur exclusively in type II fibers.

PMID- 15247032
TI  - Age-related muscle loss and progressive dysfunction in mechanosensitive growth
      factor signaling.
AB  - Loss of muscle mass and function (sarcopenia) is one of the most marked problems
      associated with aging because it has major healthcare as well as socioeconomic
      implications. The growth hormone/IGF-I axis is regarded as an important regulator
      of muscle mass. However, it is now appreciated that other tissues in addition to
      the liver express IGF-I. Also, there are local as well as systemic forms of IGF-I
      that have different functions. We cloned two different IGF-Is that are expressed
      by skeletal muscle, and both are derived from the IGF-I gene by alternative
      splicing. One of these is expressed in response to physical activity, which has
      now been called "mechanogrowth factor" (MGF). The other is similar to the
      systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I
      required for upregulating protein synthesis. MGF differs from systemic IGF-IEa in
      that it has a different peptide sequence that is responsible for activating
      muscle satellite (stem) cells. Therefore, it appears these two forms of IGF-I
      have different actions and that they are important regulators of muscle growth.
      Growth hormone treatment apparently upregulates the level of IGF-I gene
      expression, and when it is combined with resistance exercise more is spliced
      toward MGF. This results in an increase in muscle cross-sectional area in the
      elderly subjects who otherwise would produce less MGF. The possibility of
      ameliorating sarcopenia using MGF delivered as a peptide or by gene therapy will
      be discussed.

PMID- 15247033
TI  - What do hormones have to do with aging? What does aging have to do with hormones?
AB  - It is clear that aging results in alterations of endocrine physiology, which in
      turn appear to contribute to development of the senescent phenotype. How the
      underlying basic aging process or processes cause the endocrine cell dysfunctions
      leading to hormone imbalance is far from clear, but oxidative alteration of cell
      membranes is an attractive candidate mechanism that might be susceptible to some
      degree of global remediation.

PMID- 15247034
TI  - Functional efficiency of the senescent cells: replace or restore?
AB  - It is generally accepted that aging is a phenomenon of irreversibility,
      inevitability, and universality with parenchymal loss and functional decline.
      Consequently, the major goals of aging research are focused on the development of
      a replace strategy of the aged organs or cells, based on immortalizing tools,
      stem cells, or artificial substitutes. Recently, however, a new concept of
      functional recovery has been introduced on the basis of the functional
      restoration of the responsiveness of the senescent cells toward a variety of
      agonists, including growth factors. The aging phenotypes of hyporesponsiveness
      and morphological alteration are shown to be readily adjusted by modulation of
      the several membrane-associated molecules, named gatekeeper molecules, among
      which caveolin is one of the major determinants. Caveolin is the essential
      component of the caveolae, responsible for regulation of signal transduction,
      endocytosis and trancytosis, and cytoskeletal arrangement via its scaffolding
      domain. The caveolin status is associated strictly with cellular transformation,
      if depleted, and with senescent phenotype, if overexpressed. Therefore, simple
      reduction of caveolin status in senescent cells leads to restoration of the
      functional responsiveness to mitogenic stimuli and even of the cellular shape.
      These data strongly suggest that the gatekeeper molecules, represented by
      caveolin, may play the prime role in determination of the senescent phenotypes.
      From these results, it can be summarized that the replace principle would not
      necessarily be the essential one, but the restore principle can be somehow
      substituted for the betterment of the aged cells and organisms.

PMID- 15247035
TI  - Growth hormone alters components of the glutathione metabolic pathway in Ames
      dwarf mice.
AB  - Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1(IGF
      1)/insulin pathway is associated with extended life span in several species. Ames
      dwarf mice are GH and IGF-1 deficient and live 50-64% longer than wild-type
      littermates (males and females, respectively). Previously, we have shown that
      Ames mice exhibit elevated levels of antioxidative enzymes and lower oxidative
      damage. To further explore the relationship between GH and antioxidant
      expression, we administered GH or saline to dwarf mice and evaluated components
      of the glutathione (GSH) synthesis and degradation system. Growth hormone
      treatment significantly elevated kidney gamma-glutamyl-cysteine synthetase
      protein levels in 3- and 12-month-old dwarf mice. In contrast, the activity of
      the GSH degradation enzyme, gamma-glutamyl transpeptidase, was suppressed by GH
      administration in brain (P <.05), kidney (P <.01), heart (P <.005), and liver (P
      <.06). Activity levels of the detoxification enzyme, glutathione-S-transferase,
      were also suppressed in kidney tissues at 3 and 12 months of age and in 12-month
      old dwarf liver tissues (P <.05). Taken together, the current results along with
      data from previous studies support a role for growth hormone in the regulation of
      antioxidative defense and, ultimately, life span in organisms with altered GH or
      IGF-1 signaling.

PMID- 15247036
TI  - Age-related endocrine dysfunction in nonhuman primates.
AB  - Peculiarities of functioning of some parts of the endocrine system (the pineal
      gland, pancreatic gland, hypothalamic-pituitary-adrenal axis, and hypothalamic
      pituitary-testicular axis) in an aging nonhuman primate model (Papio hamadryas
      and Macaca mulatta) are described in this article. It has been established that
      basal activity of some endocrine functions (glucocorticoid, corticotropic,
      pancreatic, male estradiol producing) varies little with age. Other functions
      significantly decrease (DHEA/DHEAS-producing, pineal, testicular) or increase
      (male gonadotropic) with age. In contrast with basal activity, pronounced age
      related changes in response to specific stimuli were detected in all endocrine
      functions. Old baboons and rhesus monkeys exhibited a delay of the normalization
      of the pituitary-testicular axis, adrenal cortex, and pancreatic gland function
      after their activation in response to specific stimuli, such as LHRH, CRH, ACTH,
      and glucose. Old monkeys also demonstrate decreased HPA axis sensitivity to
      glucocorticoid regulation by negative feedback and the HPT axis to inhibitory
      effect of prolonged administration of LHRH agonist. Age-related changes in
      reactions of endocrine functions in response to specific stimulating and
      inhibiting stimuli indicate impaired resiliency of these functions. Age-related
      endocrine changes perhaps play a pathophysiological role in age function
      disorders of hormonocompetent tissues and organs and age pathology.

PMID- 15247037
TI  - Secretion of melatonin in healthy elderly subjects: a longitudinal study.
AB  - We report on a 10-year longitudinal study on 24-h serum melatonin secretion (AUC)
      in healthy human subjects. Fifty women and 53 men (aged 42-83 yr) participated in
      the study initially. Of these, 18 women and 15 men were followed for 6
      consecutive years. RESULTS: (a) Cross-sectional analysis (n = 103): A significant
      (R = -.49, P =.0001) decline in AUC melatonin with age was found in women, but
      not in men. (b) Longitudinal analysis (n = 33): Repeated-measure ANOVAs for women
      (n = 18): Time: linear F(1,17) = 5.14, P =.037. The AUC increased by about 40%
      over the six-year period. In men, there were no significant changes. CONCLUSION:
      In agreement with most cross-sectional studies, an inverse relationship was found
      between melatonin secretion and age. However, the longitudinal study showed an
      increase in melatonin secretion, indicating the presence of putative compensatory
      mechanisms during healthy aging. Changes in melatonin secretion were gender
      specific, occurring in women only.

PMID- 15247038
TI  - The proinflammatory phenotype of senescent cells: the p53-mediated ICAM-1
      expression.
AB  - Senescent cells are characterized by the activation of the tumor suppressor
      protein p53 and consequently their inability to proliferate. However, their
      phenotype is not restricted to the exhaustion of their replicative potential, as
      they also exhibit a proinflammatory phenotype, which could possibly contribute to
      the aging process. Intercellular adhesion molecule-1 (ICAM-1) is one of the
      molecules involved in inflammatory response that is overexpressed in senescent
      cells and aged tissues. Although the role of the nuclear factor-kappa B (NF-kappa
      B) signaling cascade is crucial in ICAM-1 activation, we have shown that p53
      directly activates the expression of ICAM-1 in an NF-kappa B-independent manner.
      This may link p53 to ICAM-1 function and consequently to the aging process and to
      various age-related pathologies.

PMID- 15247039
TI  - Short-term caloric restriction and sites of oxygen radical generation in kidney
      and skeletal muscle mitochondria.
AB  - Mitochondrial free radical generation is believed to be one of the principal
      factors determining aging rate, and complexes I and III have been described as
      the main sources of reactive oxygen species (ROS) within mitochondria in heart,
      brain, and liver. Moreover, complex I ROS generation of heart and liver
      mitochondria seems especially linked to aging rate both in comparative studies
      between animals with different longevities and in caloric restriction models.
      Caloric restriction (CR) is a well-documented manipulation that extends mean and
      maximum longevity. One of the factors that appears to be involved in such life
      span extension is the reduction in mitochondrial free radical generation at
      complex I. We have performed two parallel investigations, one studying the effect
      of short-term CR on oxygen radical generation in kidney and skeletal muscle
      (gastrocnemius) mitochondria and a second one regarding location of mitochondrial
      ROS-generating sites in these same tissues. In the former study, no effect of
      short-term caloric restriction was observed in mitochondrial free radical
      generation in either kidney or skeletal muscle. The latter study ruled out
      complex II as a principal source of free radicals in kidney and in skeletal
      muscle mitochondria, and, similar to previous investigations in heart and liver
      organelles, the main free radical generators were located at complexes I and III
      within the electron transport system.

PMID- 15247040
TI  - Mechanism of superoxide-mediated damage relevance to mitochondrial aging.
AB  - The damaging effects of superoxide in mitochondria leading to pathological
      disorders and aging are well documented and usually ascribed to superoxide's role
      as a precursor of reactive free radical species. However, the latest findings
      point out the importance of the nucleophilic properties of superoxide and its
      ability to regulate heterolytic enzymatic processes. Hypothetical mechanisms of
      superoxide mediation of phosphorylation and dephosphorylation reactions with
      participation of protein kinases and the apoptotic protein BAD are considered.

PMID- 15247041
TI  - Glutathione metabolism during aging and in Alzheimer disease.
AB  - The concentration of glutathione (GSH), the most abundant intracellular
      nonprotein thiol and important antioxidant, declines with age and in some age
      related diseases. The underlying mechanism, however, is not clear. The previous
      studies from our laboratory showed that the age-dependent decline in GSH content
      in Fisher 344 rats was associated with a downregulation of glutamate cysteine
      ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis. Our recent
      studies further indicated that the activity and mRNA content of glutathione
      synthase (GS), which catalyzes the second reaction in de novo GSH synthesis, were
      also decreased with age in some tissues. No age-associated change was observed in
      glutathione reductase or gamma-glutamyl transpeptidase activities. Also, although
      GSH content declined with age in both male and female mice, male mice experienced
      more dramatic age-associated decline in many tissues/organs than female mice.
      Furthermore, we found that GSH content was significantly decreased in the red
      blood cells from male Alzheimer disease patients, which was associated with
      decreases in GCL and GS activities. Finally, we showed that estrogen increased
      GSH content, GS and GR activities, and GCL gene expression in the liver of both
      male and female mice. Taken together, our results suggest that (1) GCL plays a
      critical role in maintaining GSH homeostasis under both physiological and
      pathological conditions; (2) decreased GSH content may be involved in AD
      pathology in humans; and (3) estrogen increases GSH content in mice by multiple
      mechanisms.

PMID- 15247042
TI  - Alpha-lipoic acid increases Na+K+ATPase activity and reduces lipofuscin
      accumulation in discrete brain regions of aged rats.
AB  - A convincing link between oxidative stress and neurodegenerative diseases has
      been found with the knowledge that it actually damages neuronal cells in culture.
      We analyzed the effect of DL-alpha-lipoic acid on lipofuscin and Na(+)K(+) ATPase
      in discrete brain regions of young and aged rats. In aged rats, the level of
      lipofuscin was increased, and the activity of Na(+)K(+)ATPase was decreased.
      Intraperitoneal administration of lipoic acid to aged rats led to a duration
      dependent reduction and elevation in lipofuscin and enzyme activity,
      respectively, in the cortex, cerebellum, striatum, hippocampus, and hypothalamus
      of the brain. These results suggest that lipoic acid, a natural metabolic
      antioxidant, should be useful as a therapeutic tool in preventing neuronal
      dysfunction in aged individuals.

PMID- 15247043
TI  - The bud scar-based screening system for hunting human genes extending life span.
AB  - We developed a high-throughput screening system that allows identification of
      genes prolonging life span in the budding yeast Saccharomyces cerevisiae. The
      method is based on isolating yeast mother cells with an extended number of cell
      divisions as indicated by the increased number of bud scars on their surface.
      Fluorescently labeled wheat germ agglutinin (WGA) was used for specific staining
      of bud scars. Screening of a human HepG2 cDNA expression library in yeast
      resulted in the isolation of several yeast transformants with a potentially
      prolonged life span. The budding yeast S. cerevisiae, one of the favorite models
      used to study aging, has been studied extensively for the better understanding of
      the mechanisms of human aging. Because human disease genes often have yeast
      counterparts, they can be studied efficiently in this organism. One interesting
      example is the WRN gene, the human DNA helicase, which participates in the DNA
      repair pathway. The mutation of the WRN gene causes Werner syndrome showing
      premature-aging phenotype. Budding yeast contains WRN homologue, SGS1, and its
      mutation results in shortening yeast life span. The knowledge gained from the
      studies of budding yeast will benefit studies in humans for better understanding
      of aging and aging-related disease.

PMID- 15247044
TI  - Senescence marker protein-30 as a novel antiaging molecule.
AB  - Senescence marker protein-30 (SMP30), composed of 299 amino acids, has an
      approximate molecular mass of 32-34 kDa and has a pI 4.9 in charge. The amino
      acid alignment from various animal species revealed a highly conserved structure.
      SMP30 has an enzyme activity hydrolyzing sarin, soman, and tabun, known as lethal
      toxic nerve chemicals. We analyzed the organophosphatase activity of SMP30 using
      DFP as a substrate. This DFPase activity is revealed in a dose-dependent manner
      in the presence of magnesium ions. We investigated the intracellular localization
      of SMP30. It is localized in both the cytoplasm and nucleus. To confirm the
      presence of SMP30 in the nucleus, we prepared nuclear and cytoplasmic extracts
      from isolated cultured hepatocytes. Western blotting showed that SMP30 was
      detected in both extracts. Because the expression is reduced by carbon
      tetrachloride, one can speculate that the expression is modulated by oxidative
      stress increased with aging.

PMID- 15247045
TI  - Iron accumulation during cellular senescence.
AB  - Iron accumulates as a function of age and is associated with the pathology of
      numerous age-related diseases. These changes may be caused by altered iron
      homeostasis at the cellular level, yet this is poorly understood. Therefore,
      changes in iron content in primary human fibroblasts were studied in culture
      models of cellular senescence. Total iron content increased exponentially during
      cellular senescence, reaching approximately 10-fold higher levels than young
      cells. Increasing intracellular iron levels through iron-citrate supplementation
      or decreasing intracellular iron levels using iron-selective chelators had little
      effect on cellular life span and markers of cellular senescence when used at
      subtoxic doses. However, accelerating cellular senescence with low-dose H(2)O(2)
      also accelerated senescence-associated iron accumulation. Delaying cellular
      senescence with N-tert-butyl-hydroxylamine (NtBHA) attenuated senescence
      associated iron accumulation. Furthermore, H(2)O(2) or NtBHA had no effect on
      iron intracellular levels in immortalized fibroblasts. Thus, iron accumulation is
      not a cause, but a consequence of normal cellular senescence in vitro. Senescence
      associated iron accumulation may contribute to the increased oxidative stress and
      cellular dysfunction seen in senescent cells.

PMID- 15247046
TI  - Investigations on the nature of the cost of reproduction: susceptibility to heat
      stress in fruitflies.
AB  - Studies in various species have shown that changes in reproductive activity
      result in inverse changes in life span. It is interesting to know how this "cost
      of reproduction" is incurred. It is possible that reproductive activity renders
      the organism more vulnerable to stress and that accumulated damage has a role in
      the observed decrease in life span. Previously, other investigators had shown
      that mated female fruitflies have significantly shorter life spans than virgin
      females. We compare mated and virgin young fruitflies for susceptibility to
      lethal heat stress. Preliminary results suggest that mated fruitflies are
      significantly more susceptible to heat stress than virgin ones.

PMID- 15247047
TI  - Alternative pathways might mediate toxicity of high concentrations of superoxide
      dismutase.
AB  - One of the most important antioxidant enzymes is superoxide dismutase (SOD),
      which catalyzes the dismutation of superoxide radicals to peroxide. The gene for
      CuZnSOD lies in humans on chromosome 21, and its activity is increased in
      patients with Down syndrome. However, instead of being beneficial, increased
      lipid peroxidation is associated with this increased expression, and also studies
      on bacteria and transgenic animals show that high levels of SOD actually lead to
      increased lipid peroxidation and hypersensitivity to oxidative stress. Using
      mathematical models, we investigated the question of how overexpression of SOD
      can lead to increased oxidative stress, although it is an antioxidant enzyme. We
      considered several possibilities that have been proposed in the literature, such
      as CuZnSOD-catalyzed hydroxyl radical formation, superoxide-mediated inhibition
      of membrane peroxidation, and short-circuiting of the Cu(I)ZnSOD/Cu(II)ZnSOD
      redox cycle. We found that one of the proposed mechanisms under certain
      circumstances is able to explain the increased oxidative stress caused by SOD.
      Furthermore, we identified an additional mechanism that agrees well with
      experimental observations. We call it the "alternative pathway" mechanism,
      because it depends on superoxide radicals having alternative pathways besides
      their reaction with SOD. The alternative pathway mechanism is a very general
      explanation for SOD-associated oxidative stress, because it does not depend on
      the specific type of SOD, nor on the redox status of the cell. We therefore think
      that it might be the common mechanism for the detrimental effects seen in cells
      and organisms with increased levels of the different forms of superoxide
      dismutase.

PMID- 15247048
TI  - No increase in senescence-associated beta-galactosidase activity in Werner
      syndrome fibroblasts after exposure to H2O2.
AB  - Normal human diploid fibroblasts (HDFs) exposed to a single H(2)O(2) subcytotoxic
      stress display features of premature senescence, termed stress-induced premature
      senescence (SIPS). In this work, our aim was to study SIPS in Werner syndrome
      (WS) fibroblasts, derived from a patient with WS, a disease resembling
      accelerated aging. The subcytotoxic dose for WS fibroblasts was found to be
      inferior to that of normal HDFs, indicating WS fibroblasts are more sensitive to
      hydrogen peroxide than normal HDFs. SA beta-gal activity has been shown to occur
      both in vitro and in vivo, and we studied the proportion of WS cells positive for
      SA beta-gal. Intriguingly, the percentage of positive cells did not increase with
      the dose of H(2)O(2) used. Contrary to other HDFs, the DNA-binding activity of
      p53 in WS fibroblasts did not increase in SIPS. We found, based on our results,
      that WS fibroblasts feature an altered stress response and do not reach SIPS from
      H(2)O(2). We suggest that the proportion of cells that in normal HDFs would enter
      SIPS instead die in WS fibroblasts. Last, we propose that aging derives from a
      loss of integrity of the chromatin structure, which occurs faster in WS patients.

PMID- 15247049
TI  - Aging and vitamin E deficiency are responsible for altered RNA pathways.
AB  - Fibrillar centers (FCs), dense fibrillar (DFC) and granular (GC) components in
      nucleoli, and perichromatin granules (PGs) in nucleoplasm were measured by
      morphometry. FC size and their nucleolar surface fraction significantly decreased
      in aging and vitamin E deficiency. The GC and DFC nucleolar fraction was
      unchanged in adult and old rats, but in vitamin E-deficient animals GC increased
      and DFC decreased significantly. PG density significantly increased in aging and
      decreased in vitamin E deficiency. The quantitative evaluation of immunolabeled
      transcription and splicing factors revealed that polymerase II and SC-35
      significantly decreased in old and vitamin E-deficient versus adult animals.
      Fibrillarin and snRNPs did not change between adult and old rats, but were
      significantly lower in vitamin E-deficient rats. These data document altered RNA
      pathways in aging and vitamin E deficiency. Considering the antioxidant role of
      vitamin E, they lend further support to the importance of free radical production
      and control in the aging process.

PMID- 15247050
TI  - Senescence marker protein-30 knockout mouse as an aging model.
AB  - A mouse strain lacking SMP30 can be regarded as a strain showing ultimate
      decrease of the SMP30 molecule. After three months of age, SMP30-KO mice had an
      increased mortality rate, compared with the SMP30-WT mice, all of which remained
      alive. Electron microscopic observation of the hepatocytes from 12-month-old
      SMP30-KO mice revealed many empty vacuoles, presumably lipid droplets, abnormally
      enlarged mitochondria with indistinct cristae, and exceptionally large lysosomes
      filled with electron-dense bodies. The total hepatic triglyceride concentration
      of SMP30-KO mice was approximately 3.6-fold higher than that of the age-matched
      wild type. Similarly, the total hepatic cholesterol of SMP30-KO mice reached an
      approximate 3.3-fold greater value than that of the comparative group. Total
      hepatic phospholipids of SMP30-KO mice achieved an approximately 3.7-fold higher
      level compared with that of the wild-type mice. The cells from SMP30-KO mice were
      sensitive to apoptotic reagents. Those results supported the idea that SMP30 has
      an antiapoptotic function with wide spectrum. These findings indicate that SMP30
      KO mice are highly susceptible to various harmful reagents. This strain might be
      a useful tool for aging and biological monitoring.

PMID- 15247051
TI  - Lack of correlation between mitochondrial reactive oxygen species production and
      life span in Drosophila.
AB  - The free radical theory of aging proposes that mitochondrial production of
      reactive oxygen species (ROS) determines the rate of aging. Supporting this
      hypothesis, longer-lived species produce fewer ROS than shorter-lived ones, and
      calorically restricted rodents live longer and produce fewer ROS than controls.
      We studied such correlation in Drosophila melanogaster in caloric restriction and
      in mutant flies overexpressing the mitochondrial adenine nucleotide translocase
      (ANT). Caloric restriction extended life span, but there was no significant
      difference in mitochondrial ROS production compared with controls. ANT
      overexpressers had significantly lower ROS production (because they had lower
      membrane potential), but their life span was not extended compared to wild type.
      Our results show two examples in which mitochondrial ROS production and life span
      are not correlated.

PMID- 15247052
TI  - Malondialdehyde and measures of antioxidant activity in subjects from the Belfast
      Elderly Longitudinal Free-living Aging Study.
AB  - Glutathione and glutathione peroxidase activity are important components in the
      complex body defense against oxidative damage. In this study, we have measured
      malondialdehyde (MDA) as a marker of oxidative stress, the antioxidant
      glutathione (GSH), and activity of the antioxidant enzyme (GSHPx), in a cohort of
      free-living elderly subjects from the Belfast Elderly Longitudinal Free-living
      Aging STudy (BELFAST), hypothesizing that free-living Senieur-approximated
      nonagenarians might demonstrate enhanced antioxidant defense mechanisms. The main
      finding in the BELFAST octo/nonagenarians was that plasma antioxidant glutathione
      increased in nonagenarian compared with septo/octogenarian subjects (P =.015),
      whereas conversely antioxidant glutathione peroxidase activity fell in the
      nonagenarian group (P <.0001). In the same subject group, malondialdehyde, a
      measure of lipid peroxidation, showed no change across the age groups (P =.73).
      These results might overall represent a situation in which elderly survivors in
      the BELFAST study have evolved a sort of free radical/antioxidant equilibrium as
      a mechanism of successful aging.

PMID- 15247053
TI  - Regenerative medicine: Antagonic-Stress therapy in distress and aging. I.
      Preclinical synthesis--2003.
AB  - Repetitive and cumulative distress (acute and/or chronic, psychic and/or
      biologic) and aging processes (impairment phenomena, agglomerated, and
      accumulated with the passing of life and senescence periods), as well as distress
      <==> aging reciprocal amplification-accelerating-aggravation relationships
      require strong and rational (etiopathogenic) therapeutic interventions.
      Therefore, the drug, Antagonic-Stress (AS)--a new integrative therapy, with
      specific synergistic formula, being patented worldwide--becomes an important
      solution in distress, senescence, and their related pathologies. In acute
      (contention) stress, AS treatment significantly decreased rat mortality, number
      and surface of stomach ulcerations, nonesterified fatty acids (NEFAs), and
      increased superoxide dismutase (SOD) from blood. In chronic psychic stress, live
      nerve cells selectively isolated from rat cerebral cortex were highly protected
      by the administration of AS. In addition, antistress and antiaging homeostatic
      actions of AS were demonstrated in accelerated senescence (aging + distress) at
      multiple brain levels: on functional anabolism [increase in total ribonucleic
      acids (RNA), total proteins (TP), and water-soluble proteins (WSP)]; on
      functional catabolism [decrease in water-insoluble proteins (WIP)]; on structural
      anabolism (increased regeneration of free ribosomes, rough endoplasmic reticulum,
      mitochondria, and Nissl bodies); on structural catabolism (lipofuscinolysis and
      ceroidolysis, neurono-glial transfer of lipopigment continuously processed and
      dissoluted, and finally capillary elimination). Preclinical research with AS
      demonstrated important regenerative processes in the key organs (liver, heart,
      and brain), which mostly suffer due to both distress and senescence.

PMID- 15247054
TI  - Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related
      diseases. II. Clinical review--2003.
AB  - Distress and senescence, their reciprocal aggravating-quickening connections, and
      their related pathologies have a large worldwide impact on healthcare systems in
      this new millennium. For this reason, Antagonic-Stress (AS)--an advanced
      integrative therapy, with specific synergistic composition, and patented
      internationally--represents a significant strategy in health, aging, and
      longevity. Clinical research with AS proves the drug's efficacy in the management
      of distress (neurotic, stress-related, and affective disorders; behavioral
      syndromes associated with physiological disturbances and physical factors; mental
      and behavioral disorders due to psychoactive substance uses) and psychogeriatrics
      [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial
      psychopathological instruments and psychometric tests in multiple assessments
      used for gerontopsychiatry demonstrated strong improvements after AS
      administration in early-moderate stages of Alzheimer or vascular dementia, as
      well as in other OMD. In addition, comparative clinical studies evinced the
      superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate
      (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These
      comparative clinical trials agreed closely with comparative preclinical research
      and confirmed AS synergistic homeostatic, adaptogenic, antioxidative,
      cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective
      actions against oxidative stress recommend this orthomolecular therapy in stress,
      aging, and free radical pathology.

PMID- 15247055
TI  - Delaying the mitochondrial decay of aging.
AB  - Mitochondrial dysfunction may be a principal underlying event in aging, including
      the degenerative diseases of aging such as brain degeneration. Mitochondria
      provide energy for basic metabolic processes, and their decay with age impairs
      cellular metabolism and leads to cellular decline. Progress over the last decade
      in delaying the mitochondrial decay of aging is reviewed.

PMID- 15247056
TI  - Development of calorie restriction mimetics as a prolongevity strategy.
AB  - By applying calorie restriction (CR) at 30-50% below ad libitum levels, studies
      in numerous species have reported increased life span, reduced incidence and
      delayed onset of age-related diseases, improved stress resistance, and
      decelerated functional decline. Whether this nutritional intervention is relevant
      to human aging remains to be determined; however, evidence emerging from CR
      studies in nonhuman primates suggests that response to CR in primates parallels
      that observed in rodents. To evaluate CR effects in humans, clinical trials have
      been initiated. Even if evidence could substantiate CR as an effective antiaging
      strategy for humans, application of this intervention would be problematic due to
      the degree and length of restriction required. To meet this challenge for
      potential application of CR, new research to create "caloric restriction
      mimetics" has emerged. This strategy focuses on identifying compounds that mimic
      CR effects by targeting metabolic and stress response pathways affected by CR,
      but without actually restricting caloric intake. Microarray studies show that
      gene expression profiles of key enzymes in glucose (energy) handling pathways are
      modified by CR. Drugs that inhibit glycolysis (2-deoxyglucose) or enhance insulin
      action (metformin) are being assessed as CR mimetics. Promising results have
      emerged from initial studies regarding physiological responses indicative of CR
      (reduced body temperature and plasma insulin) as well as protection against
      neurotoxicity, enhanced dopamine action, and upregulated brain-derived
      neurotrophic factor. Further life span analyses in addition to expanded toxicity
      studies must be completed to assess the potential of any CR mimetic, but this
      strategy now appears to offer a very promising and expanding research field.

PMID- 15247057
TI  - Interventions in aging and age-associated pathologies by means of nutritional
      approaches.
AB  - So-called antioxidant strategies have not been shown convincingly to be effective
      in increasing life spans of animals. Thus, the general consensus of experimental
      gerontology in the last century was that the only reproducible means of
      prolonging survivals of animals is the calorie restriction paradigm. As a
      challenge against this dogma, we attempted to examine the effect of two potent
      antioxidants, one tetrahydrocurcumin (a biotransformed metabolite of curcumin
      contained in turmeric of Indian curry) and the other green tea polyphenols.

PMID- 15247058
TI  - Absolute versus relative caloric intake: clues to the mechanism of calorie/aging
      rate interactions.
AB  - It has been suggested that the influence of caloric intake on aging rate is not
      due to the absolute number of calories ingested. Instead, aging rate is altered
      only when there is a disparity between the actual caloric intake and that which
      would be ingested if the food supply were unlimited. This review will discuss a
      few of the studies supporting this viewpoint.

PMID- 15247059
TI  - Acetyl-L-carnitine dietary supplementation to old rats increases mitochondrial
      transcription factor A content in rat hindlimb skeletal muscles.
AB  - Acetyl-L-carnitine (ALCAR) fed to old rats has been reported to partially restore
      mitochondrial function and ambulatory activity. The results of the effect of
      ALCAR dietary supplementation to 28-month-old rats on mitochondrial transcription
      factor A (TFAM) content of rat hindlimb skeletal muscles are reported.

PMID- 15247060
TI  - An appetite for death.
AB  - A diverse array of organisms live longer under dietary restriction. Here, a
      hypothesis is proposed as a framework for interpreting this phenomenon. Dietary
      restriction is explained in terms of evolution and antagonistic pleiotropy.
      Focusing on the decline in reproductive capacity seen in dietary restriction, it
      is submitted that "normal" appetite is geared toward producing a neuroendocrine
      and metabolic internal milieu optimized for reproduction, with long-term
      detrimental effects on health as a by-product. In dietary restriction
      experiments, the animal is prevented from eating enough to attain this internal
      milieu and, as a by-product, lives longer.

PMID- 15247061
TI  - Reproductive switch and aging: the case of leptin change in dietary restriction.
AB  - We have proposed that normal food intake is geared toward optimizing the internal
      milieu for reproduction, despite some components of this milieu being detrimental
      to health. In dietary restriction, the animal is prevented from eating enough to
      attain or maintain reproductive capacity and this particular milieu does not
      materialize. Life extension occurs as a by-product. This idea provides a
      framework for exploring biomolecular changes in dietary restriction and their
      relevance to aging. Leptin is a case in point: here, a decrease in leptin level
      in dietary restriction is explored in the light of leptin's role in the complex
      signaling system of reproductive switch.

PMID- 15247062
TI  - Long-lived alpha MUPA transgenic mice exhibit increased mitochondrion-mediated
      apoptotic capacity.
AB  - Caloric restriction (CR) is currently the only therapeutic intervention known to
      attenuate aging in mammals, but the mechanisms underlying this phenomenon are
      still poorly understood. To study this issue, the transgenic model of alpha MUPA
      mice, which previously were reported to spontaneously eat less and live longer
      compared with their wild-type (WT) control mice, were used. Currently, two
      transgenic lines that eat less are available, thus implicating the transgenic
      enzyme, that is, the urokinase-type plasminogen activator (uPA), in causing the
      reduced appetite. Recently, several changes in the alpha MUPA liver were noted,
      at the mitochondrial and cellular level, which consistently pointed to an
      enhanced capacity to induce apoptosis. In addition, alpha MUPA mice showed a
      reduced level of serum IGF-1 and a reduced incidence of spontaneously occurring
      or carcinogen-induced tumors in several tissues. Overall, the alpha MUPA model
      suggests that long-lasting, moderately increased apoptotic capacity, possibly
      linked in part to modulation of serum IGF-1 and mitochondrial functions, could
      play a role in the attenuation of aging in calorically restricted mice.

PMID- 15247063
TI  - Effect of caloric restriction on the 24-hour plasma DHEAS and cortisol profiles
      of young and old male rhesus macaques.
AB  - Although dietary caloric restriction (CR) can retard aging in laboratory rats and
      mice, it is unclear whether CR can exert similar effects in long-lived species,
      such as primates. Therefore, we tested the effect of CR on plasma levels of
      dehydroepiandrosterone sulfate (DHEAS), a reliable endocrine marker of aging. The
      study included six young (approximately 10 years) and ten old (approximately 25
      years) male rhesus macaques, approximately half of the animals in each age group
      having undergone >4 years of 30% CR. Hourly blood samples were collected remotely
      for 24 hours, through a vascular catheter, and assayed for DHEAS and cortisol.
      Both of these adrenal steroids showed a pronounced diurnal plasma pattern, with
      peaks occurring in late morning, but only DHEAS showed an aging-related decline.
      More importantly, there was no significant difference in plasma DHEAS
      concentrations between the CR animals and age-matched controls. These data fail
      to support the hypothesis that CR can attenuate the aging-related decline in
      plasma DHEAS concentrations, at least not when initiated after puberty.

PMID- 15247064
TI  - Caloric restriction modulates early events in insulin signaling in liver and
      skeletal muscle of rat.
AB  - Mutations that extend life span in C. elegans suggest that the insulin/IGF-1
      signaling (IS) pathway may play a key role in retarding aging and extending life
      span by caloric restriction (CR). To evaluate this hypothesis, male rats were
      subjected to either AL (ad libitum) or CR (40% from AL) for 2 and 25 months, and
      then the effects of CR on the early events in the IS pathway in liver and muscle
      were assessed. The results indicated that aging was accompanied by a significant
      decline in insulin receptor tyrosine phosphorylation (pY-IR) upon insulin
      stimulation in both tissues, which was correlated with a significant increase in
      the activity of protein tyrosine phosphatase 1B (PTP-1B). However, these
      alterations with age were attenuated by 25CR. Parallel changes observed in liver
      mRNA of CR rats were upregulated insulin receptor (IR), IGF-1R and IRS-1, but
      increased expression of IR mRNA was dissociated with the IR protein in 25CR rats.
      The expression of liver mRNAs involved in lipid metabolism was also analyzed. In
      contrast to 25AL rats, the expression of mRNAs for PPARs (alpha, delta, and
      gamma) was significantly increased in 25CR rats. SREBP-1c and fatty acid synthase
      were reduced, and other genes were increased, including hormone-sensitive lipase
      and PGC-1 by CR. The data suggest that the normal function of insulin receptor in
      liver and muscle is required for successful aging. An altered expression of
      transcription of a number of genes involved in lipid metabolism may also
      contribute to modulation of the IS pathway by CR.

PMID- 15247065
TI  - Aging, exercise, and phytochemicals: promises and pitfalls.
AB  - Phytochemicals are emerging comprehensive and versatile sources of antioxidants
      to be consumed to enhance the body's defenses against harmful reactive oxygen
      species generated endogenously or exogenously. Tocols, favonoids, and phenolic
      acids compose the majority of this class of antioxidants, although more complex
      compounds may also be involved, such as ginsenosides. In vitro and in vivo
      studies have demonstrated convincingly that dietary supplementation of
      phytochemicals has beneficial effects against certain types of pathogenesis,
      disease, cancer, and aging. There is evidence that these effects are related to
      the ability of phytochemicals to promote the antioxidant defense system and
      reduce oxidative stress and damage in the cell. However, due to their structural
      and chemical diversity and complexity, many of the benefits as well as potential
      adverse effects remain to be examined.

PMID- 15247066
TI  - Aging, exercise, and cardioprotection.
AB  - Myocardial ischemia-reperfusion (I-R) injury is a major contributor to the
      morbidity and mortality associated with coronary artery disease. The incidence of
      I-R events is greatest in older persons, and studies also indicate that the
      magnitude of myocardial I-R injury is greater in senescent individuals compared
      to younger adults. Regular exercise has been confirmed as a pragmatic
      countermeasure to protect against I-R-induced cardiac injury. Specifically,
      endurance exercise has been proven to provide cardioprotection against an I-R
      insult in both young and old animals. Proposed mechanisms to explain the
      cardioprotective effect of exercise include the induction of myocardial heat
      shock proteins (HSPs), improved cardiac antioxidant capacity, and/or elevation of
      other cardioprotective proteins. Of these potential mechanisms, evidence
      indicates that elevated myocardial levels of heat shock proteins or antioxidants
      can provide myocardial protection against I-R injury. At present, which of these
      protective mechanisms is essential for exercise-induced cardioprotection remains
      unclear. Understanding the molecular basis for exercise-induced cardioprotection
      is important in developing exercise paradigms to protect the heart during an I-R
      insult.

PMID- 15247067
TI  - Regular exercise: an effective means to reduce oxidative stress in old rats.
AB  - A healthy diet and regular exercise are among the major factors that influence
      quality of life (QOL) in old age. Exercise is believed to be beneficial to
      improve QOL, retarding age-related decline of physiological functions and
      preventing age-related diseases. Regular physical exercise can possibly improve
      age-related functional decline and delay onset of age-related diseases by
      attenuating potentially harmful oxidative damage and suppressing inflammatory
      processes even in older age.

PMID- 15247068
TI  - Mechanisms in muscle atrophy in immobilization and aging.
AB  - The purpose of this report was to study the effects of four weeks of hindlimb
      immobilization on acid phosphatase activity of old rats in comparison with the
      profile obtained after similar treatment in young rats.

PMID- 15247069
TI  - Effect of physical activity levels on bone strength.
AB  - The present study employs statistical analysis using age as the covariate and
      seeks to provide cross-sectional data concerning the relationship between bone
      strength and levels of physical activities among Japanese.

PMID- 15247070
TI  - Naturally long-lived animal models for the study of slow aging and longevity.
AB  - Judicious selection of new animal models for the study of basic aging processes
      must combine feasibility and good use of the comparative method with evidence of
      antiaging adaptations, like the ability to combat oxidative damage to cells and
      tissues. A number of vertebrate species already in use or being developed as new
      biomedical models lend themselves very well to laboratory studies of aging,
      including small birds, bats, and mole-rats.

PMID- 15247071
TI  - The extreme aged: sampling, measurement, and statistical models in cross
      sectional estimation and forecasting.
AB  - Little effort has been directed toward studying the relationship between
      morbidity and mortality at exceptional ages, perhaps for no better reason than it
      has been difficult to do given available data resources. Two study
      innovations/adjustments are required to adequately represent count data with
      reports of health from aged sample persons. These design features are
      oversampling of the exceptional group and linkage to detailed administrative
      reports. The National Long-Term Care Survey (NLTCS) has made it possible to study
      health and functioning in the context of exceptional longevity.

PMID- 15247072
TI  - Demographics of human supercentenarians and the implications for longevity
      medicine.
AB  - Demographers have forecast that there are going to be a great many more older
      adults in the next few decades. This will have great implications for longevity
      medicine. The Gerontology Research Group, affiliated with the UCLA School of
      Medicine, has compiled and maintained a Table of Worldwide Living
      Supercentenarians (persons 110 years or older) for the last 4 years, shedding
      important light on the biological limits of human morbidity and mortality and
      providing a realistic perspective on the problem of long-term interventions that
      can reasonably be achieved in the near future.

PMID- 15247073
TI  - Early-life programming of aging and longevity: the idea of high initial damage
      load (the HIDL hypothesis).
AB  - In this study, we test the predictions of the high initial damage load (HIDL)
      hypothesis, a scientific idea that early development of living organisms produces
      an exceptionally high load of initial damage, which is comparable with the amount
      of subsequent aging-related deterioration accumulating during the rest of the
      entire adult life. This hypothesis predicts that even small progress in
      optimizing the early-developmental processes can potentially result in a
      remarkable prevention of many diseases in later life, postponement of aging
      related morbidity and mortality, and significant extension of healthy life span.

PMID- 15247074
TI  - Cardiovascular disease delay in centenarian offspring: role of heat shock
      proteins.
AB  - Cardiovascular disease is a major cause of morbidity and mortality of older
      Americans. We have demonstrated recently that centenarian offspring, when
      compared with age-matched controls, avoid and/or delay cardiovascular disease and
      cardiovascular risk factors. Given recent evidence suggesting that higher
      circulating levels of HSP70 predict the future development of cardiovascular
      disease in established hypertensives and a recent study demonstrating a decrease
      in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be
      lower in centenarian offspring compared with controls. The circulating serum
      concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was
      analyzed using a modified HSP70 ELISA method. Centenarian offspring showed
      approximately 10-fold lower levels of circulating serum HSP70 compared with
      spousal controls (P <.001). The exact biological significance of the extremely
      low levels of circulating serum HSP70 observed in centenarian offspring thus far
      is not clear. However, circulating HSP has been shown to correlate in diseases or
      disorders in which there is destruction or damage to target tissues or organs,
      including cardiovascular diseases and numerous autoimmune disorders. We
      hypothesize that low levels of circulating serum HSP70 may be an indicator of a
      healthy state and point to longevity of the host; therefore, our results suggest
      that levels of circulating serum HSP70 may be a marker for longevity.

PMID- 15247075
TI  - Testing the free radical theory of aging in bats.
AB  - The extended longevity of bats, despite their high metabolic rates, may provide
      insight to patterns and mechanisms of aging. I tested the free radical theory of
      aging as an explanation for the extreme longevity of the little brown bat, Myotis
      lucifugus (maximum life span potential [MLSP] = 34 years). In a comparative
      study, I measured whole-organism oxygen consumption and mitochondrial hydrogen
      peroxide production in brain, heart, and kidney tissues from M. lucifugus and
      short-tailed shrews, Blarina brevicauda (MLSP = 2 years). As predicted by the
      free radical theory of aging, M. lucifugus produced approximately half the amount
      of hydrogen peroxide as B. brevicauda. In addition, I compared oxygen consumption
      and hydrogen peroxide production of adult (approximately 1 year) and juvenile
      (fully developed and fledged young of the year) M. lucifugus to assess oxidative
      damage to mitochondria (measured as an increase in hydrogen peroxide production)
      due to the high metabolic rate associated with flight. Contrary to my prediction,
      juveniles had significantly higher levels of hydrogen peroxide production than
      adults. I propose that the decreased free radical production in adults is the
      result of within-individual selection of efficient mitochondria due to selective
      pressure created by the high energetic demands of flight.

PMID- 15247076
TI  - The reliability-engineering approach to the problem of biological aging.
AB  - We applied reliability theory to explain aging of biological species and came to
      the following conclusions: (1) Redundancy is a key notion for understanding aging
      and the systemic nature of aging in particular. Systems, which are redundant in
      numbers of irreplaceable elements, do deteriorate (i.e., age) over time, even if
      they are built of nonaging elements. (2) An apparent aging rate or expression of
      aging (measured as age differences in failure rates, including death rates) is
      higher for systems with higher redundancy levels. (3) Redundancy exhaustion over
      the course of life explains the observed compensation law of mortality (mortality
      convergence at later life) as well as the observed late-life mortality
      deceleration, leveling-off, and mortality plateaus. (4) Living organisms seem to
      be formed with a high load of initial damage, and therefore their life span and
      aging patterns may be sensitive to early-life conditions that determine this
      initial damage load during early development.

PMID- 15247077
TI  - Does exceptional human longevity come with a high cost of infertility? Testing
      the evolutionary theories of aging.
AB  - The purpose of this study is to test the prediction of the evolutionary theory of
      aging that human longevity comes with the cost of impaired reproductive success
      (higher infertility rates). Our validation study is based on the analysis of
      particularly reliable genealogical records for European aristocratic families
      using a logistic regression model with childlessness as a dependent (outcome)
      variable, and woman's life span, year of birth, age at marriage, husband's age at
      marriage, and husband's life span as independent (predictor) variables. We found
      that the woman's exceptional longevity did not increase her chances of being
      infertile. It appears that the previous reports by other authors of high
      infertility among long-lived women (up to 50% infertility) are related to
      incomplete data, that is, births of children not reported. Thus, the concept of
      the high cost of infertility for human longevity is not supported by the data
      when these data are carefully cross-checked, cleaned, and reanalyzed.

PMID- 15247078
TI  - Emerging area of aging research: long-lived animals with "negligible senescence".
AB  - Field observations have suggested for quite some time that certain fish, turtles,
      and invertebrates have extremely long maximum life span potential. Age validation
      techniques have since confirmed these observations, but scientific analysis to
      understand the genetic and biochemical basis of this longevity has occurred only
      recently. The Centenarian Species and Rockfish Project now encompasses 13 pilot
      research projects, including such diverse investigations as histology, a cDNA
      library, and mitochondrial mutation analysis. In this document, the term
      "negligible senescence" is defined, and its background is given; age validation
      techniques are listed, and the various projects to date, including research
      results, are summarized.

PMID- 15247079
TI  - Functional aging and gradual senescence in zebrafish.
AB  - Zebrafish (Danio rerio) has been recognized as a powerful model for genetic
      studies in developmental biology. Recently, the zebrafish system also has given
      insights into several human diseases such as neurodegenerative, hematopoietic,
      and cardiovascular disease, and cancer. Because aging processes affect these and
      various other human disorders, it is important to compare zebrafish and mammalian
      senescence. However, the aging process of zebrafish remains largely unexplored,
      and little is known about functional aging and senescence in zebrafish. In our
      initial studies to assess aging phenotypes in zebrafish, we have identified
      several potential aging biomarkers in an ongoing search for suitable ones on
      zebrafish aging. In aging zebrafish, we detected senescence-associated beta
      galactosidase activity in skin and oxidized protein accumulation in muscle. On
      the other hand, we did not observe lipofuscin granules (aging pigments), which
      accumulate in postmitotic cells, in muscle of zebrafish with advancing age.
      Consistently, there were continuously proliferating myocytes that incorporated
      BrdU in muscle tissues of the aged fish. Moreover, we demonstrated that zebrafish
      have constitutively abundant telomerase activity in adult somatic tissues
      implicating unlimited replicative ability of cells throughout their lives.
      Although some stress-associated markers are upregulated and minor histological
      changes are observed during the aging process of zebrafish, our studies together
      with other evidence of remarkable reproductive and regenerative abilities suggest
      that zebrafish show very gradual senescence. By using those biological and
      biochemical aging markers already characterized in normal zebrafish, transgenic
      fish analyses and genetic mutant fish screens can be readily performed. These
      efforts will help to elucidate the role and molecular mechanisms of common or
      different pathways of aging among vertebrates from fish to humans and also will
      contribute to the discovery of potential drugs applicable to age-associated
      diseases in the future.

PMID- 15247080
TI  - Immortal ethics.
AB  - This article draws on ideas published in my "Intimations of Immortality" essay in
      Science (Vol. 288, No. 5463, p. 59, April 7, 2000) and my "Intimations of
      Immortality-The Ethics and Justice of Life Extending Therapies" in editor Michael
      Freeman's Current Legal Problems (Oxford University Press 2002: 65-97). This
      article outlines the ethical issues involved in life-extending therapies. The
      arguments against life extension are examined and found wanting. The consequences
      of life extension are explored and found challenging but not sufficiently
      daunting to warrant regulation or control. In short, there is no doubt that
      immortality would be a mixed blessing, but we should be slow to reject cures for
      terrible diseases that may be an inextricable part of life-extending procedures
      even if the price we have to pay for those cures is increasing life expectancy
      and even creating immortals. Better surely to accompany the scientific race to
      achieve immortality with commensurate work in ethics and social policy to ensure
      that we know how to cope with the transition to parallel populations of mortals
      and immortals as envisaged in mythology.

PMID- 15247081
TI  - Collective suttee: is it unjust to develop life extension if it will not be
      possible to provide it to everyone?
AB  - If we can anticipate that life extension will be too expensive to provide to
      everyone, is that a reason not to research and develop it? Collective suttee is
      the policy of inhibiting or prohibiting life extension on such grounds: just as
      widows are killed on their husbands' funeral pyres, potential Methuselahs would
      not be allowed to outlive everyone else. However, in other contexts we judge that
      taking from the haves is unjustified when doing so confers a merely marginal
      benefit--or no benefit--to the have-nots. By this standard, collective suttee is
      probably unjustified, for the burdens borne by the have-nots are likely to be too
      small to justify denying extra decades or centuries to those who can afford it.

PMID- 15247082
TI  - Biogerontologists' duty to discuss timescales publicly.
AB  - Aging is unpopular with the general public-but, it would seem, only up to a
      point. Treatments that claim (sometimes justifiably) to extend the total and/or
      healthy life span of elderly people, or even just make them look younger, are
      welcomed with open wallets throughout the world. If, however, one suggests to the
      typical nonbiologist-or even to the typical nongerontologist biologist-that we
      should therefore aim, in due course, to take this desire to its logical
      conclusion and bring aging under the same degree of control that we currently
      have over most infectious diseases, one is nearly always met with strong and
      sometimes strident opposition. I argue here that the prevalence of this outright
      irrationality is largely the fault of gerontologists themselves. Most people
      harbor a deep-seated fear of profound change in their lives and embrace it only
      after extensive soul-searching to convince themselves of its benefit. It cannot
      and should not be denied that a postaging world would be as profoundly different
      from today's as we can imagine. Hence, when given the opportunity to postpone
      sober consideration of its pros and cons, most people leap at that opportunity.
      It is provided to them by the nearly universal refusal of gerontologists to
      speculate about the timescales within which truly effective rejuvenation
      therapies may be developed. I suggest that this reticence, while appropriate in
      purely scientific fields, is hugely irresponsible in a biomedical discipline,
      because of its potential to delay the development of such therapies by denying
      them the funding that would be forthcoming if society had greater optimism
      concerning their foreseeability. Arguments that such funding, and/or the public's
      trust in scientists, would be short-lived if timescale predictions were not borne
      out are too flimsy to outweigh this. A further danger is the avoidable loss of
      life following the development of rejuvenation therapies that would result from
      inadequate ability to provide them universally; here again, scientists today can
      minimize this loss of life by agitating for forward planning by government, which
      will only occur when policymakers' minds are concentrating on timescale
      predictions.

PMID- 15247083
TI  - The pitfalls of planning for demographic change.
AB  - As we begin to understand the biology of aging, it will be ever more tempting to
      try to plan for the social consequences of the coming biomedical interventions in
      this arena. However, this will remain a daunting task, because the larger
      consequences of the arrival of antiaging interventions will greatly depend on the
      relative character and timing of the specific procedures that emerge. Three basic
      classes of interventions are likely: ones that slow aging in adults, ones that
      reverse aging in adults, and embryonic interventions that modify the overall
      trajectory of human aging. The consequences of each will differ significantly in
      the time required before noticeable demographic shifts begin to manifest in the
      human population, and in the social and political changes the interventions
      evoke. The specific societal consequences generally will arrive long before the
      demographic ones, and will hinge on the technical details of the interventions
      themselves--their complexity, physiological targets, modes of delivery, costs,
      unpleasantness, and the character and frequency of side effects.

PMID- 15247084
TI  - Report on the open discussion on the future of life extension research.
AB  - Following a highly stimulating series of talks on the social and ethical
      implications of greatly extended life spans, a discussion of the issues was held,
      in which a series of straw polls was conducted. An alarming conclusion from these
      polls was that most participants thought it either probable or "not improbable"
      that comprehensive functional rejuvenation of middle-aged mice would be possible
      within 10-20 years, but also felt that biogerontologists should not yet discuss
      timescales (either for mouse rejuvenation or similar progress in humans) in
      society at large. This combination of views may be very dangerous, as it assumes
      that humanity will need little forward planning to transition smoothly from its
      current almost universal fatalism concerning the defeat of aging to a widespread
      appreciation of its foreseeability or even imminence.

PMID- 15247085
TI  - Mechanisms of hormesis through mild heat stress on human cells.
AB  - In a series of experimental studies, it was shown that repetitive mild heat
      stress has antiaging hormetic effects on growth and various other cellular and
      biochemical characteristics of human skin fibroblasts undergoing aging in vitro.
      We have reported the hormetic effects of repeated challenge at the levels of
      maintenance of stress protein profile; reduction in the accumulation of
      oxidatively and glycoxidatively damaged proteins; stimulation of the proteasomal
      activities for the degradation of abnormal proteins; improved cellular resistance
      to ethanol, hydrogen peroxide, and ultraviolet-B rays; and enhanced levels of
      various antioxidant enzymes. Detailed analysis of the signal transduction
      pathways to determine alterations in the phosphorylation and dephosphorylation
      states of ERK, JNK, and p38 MAP kinases as a measure of cellular responsiveness
      to mild and severe heat stress is in progress. Furthermore, comparative studies
      using nonaging immortal cell lines, such as SV40-transformed human fibroblasts,
      spontaneous osteosarcoma cells, and telomerase-immortalized human bone marrow
      cells are also in progress for establishing differences in normal and cancerous
      cells for their responsiveness to mild and severe stresses.

PMID- 15247086
TI  - The arrest of biological time as a bridge to engineered negligible senescence.
AB  - Biological systems can remain unchanged for several hundred years at cryogenic
      temperatures. In several hundred years, current rapid scientific and technical
      progress should lead to the ability to reverse any biological damage whose
      reversal is not forbidden by physical law. We therefore explore whether
      contemporary people facing terminal conditions might be preserved well enough
      today for their eventual recovery to be compatible with physical law. The
      ultrastructure of the brain can now be excellently preserved by vitrification,
      and solutions needed for vitrification can now be distributed through organs with
      retention of organ viability after transplantation. Current law requires a few
      minutes of cardiac arrest before cryopreservation of terminal patients, but dogs
      and cats have recovered excellent brain function after 16-60 min of complete
      cerebral ischemia. The arrest of biological time as a bridge to engineered
      negligible senescence, therefore, appears consistent with current scientific and
      medical knowledge.

PMID- 15247087
TI  - Apolipoprotein E genotype and age at menopause.
AB  - We tested the hypothesis that there is a connection between apolipoprotein E
      (APOE) genotype and age at menopause. A sample of women aged between 50 and 60
      years who had reached natural menopause was studied. Survival analysis of data
      showed a significant relationship between APOE genotype and age at menopause,
      carriers of the APOE4 allele reaching menopause at an earlier age. Our findings
      can have a bearing on the question of the evolution of this major human
      polymorphism and human life history. These findings are also relevant to the
      question of the connection between reproductive parameters and age-associated
      diseases.

PMID- 15247088
TI  - The molecular chaperones and the phenomena of cellular immortalization and
      apoptosis in vitro.
AB  - The molecular chaperones are housekeeping molecules that assist in the folding
      and prevention of the aggregation of proteins and nucleotides, as well as
      participating in the elimination of ubiquitinated molecules. Evidence is reviewed
      to suggest that the Werner protein is a DNA chaperone and also that an increase
      in the expression of the molecular chaperones is the common denominator in the
      extension of cellular and species longevity as well as in the process of cellular
      immortalization, the inherent immortality of germ cells, and the inhibition of
      cellular apoptosis. It is possible that the immortalization of normal somatic
      cells is caused by an accidental reprogramming of the genome, recreating the
      chaperone expression of the germ cells. It is suggested that the molecular
      chaperones are evolution facilitators determining the life span of individual
      cells as the evolution of longevity in species.

PMID- 15247089
TI  - Cirrhosis progression as a model of accelerated senescence: affecting the
      biological aging clock by a breakthrough biophysical methodology.
AB  - To test new treatment modalities, a pilot study with a novel noninvasive
      biophysical methodology (Delta-S DVD) that can artificially exert a "decrease of
      entropy" through the patented electromagnetic-driven delivery of "energy
      clusters" was designed. This process has been modulated and integrated by the
      body as a "self" source to support the energy-dependent functional stores, thus
      modifying reparative into regenerative mechanisms of liver parenchyma. Seven long
      standing hepatitis C virus-positive (Child A-B) cirrhosis patients with overt
      symptoms and portal hypertension and failure or side effects of antiviral drug
      treatment underwent 40-min sessions of Delta-S DVD daily for six months and were
      followed up monthly. At the end of the first month, rapid improvement of symptoms
      and a decrease of portal hypertension were noted. At the end of treatment, all
      patients showed either a complete (80%) or a partial (20%) regression of fatigue
      (FISK score), peripheral edema, pruritus, and palmar erythema. As observed,
      despite having stopped beta-blockers, F1 esophageal varices disappeared (60%),
      whereas F2 decreased to F1. The Doppler ultrasound aspect of partial (40%) or
      total (20%) atrophy was either reduced (60%) or reverted to normal (20%), and the
      respiratory dynamics of the portal vein improved (80%) or normalized (20%),
      whereas gross scarring nodules disappeared in 40% of cases. These promising data
      pave the way for an innovative physiopathological approach with extensive
      clinical applications.

PMID- 15247090
TI  - How an individual fecundity pattern looks in Drosophila and medflies.
AB  - Reproduction usually is characterized by a mean-population fecundity pattern.
      Such a pattern has a maximum at earlier ages and a subsequent gradual decline in
      egg production. It is shown that individual fecundity trajectories do not follow
      such a pattern. In particular, the regular individual fecundity pattern has no
      maximum so that experimentally observed maximums are average-related artifacts.
      The three-stage description of individual fecundity, which includes maturation,
      maturity, and reproductive senescence, is more appropriate. Data are presented
      for Drosophila and Mediterranean fruitfly females that clearly confirm this
      hypothesis. A systematic error between egg-laying scores and the regular
      individual pattern allows for evaluation of how close the random scores are to
      the pattern. The first finding of the analysis of the systematic errors is that
      they are consistent with the three-stage hypothesis and do not contradict the
      absence of the maximum in the regular individual pattern. The other finding is
      the existence of obvious dynamic properties of the systematic error. The slow
      decrease in egg-laying at the maturity stage might be the result of a cost of
      mating. It can also be a consequence of "structural" senescence, that is, a slow
      rate accumulation of oxidative damage in the gonads.

PMID- 15247091
TI  - Mitochondria, sex, and mortality.
AB  - It has been proposed that prior to the evolution of sex, the endosymbiotic
      relationship between mitochondria and nuclear genomes would have selected
      mechanisms that maintained the optimum interaction between the two genomes. Once
      sex evolved, mating would introduce different, competitive, mtDNA and/or nDNA
      gene products that could well upset the balance. Mechanisms, such as the specific
      degradation of one mitochondrial genome that is known to occur, could have been
      selected to prevent part of such competition. Unlike most protein complexes in
      the cell, the proteins of the multienzyme complexes of the ox-phos system are
      derived from both nuclear-genome-coded genes and mitochondrial-genome-coded
      genes. Minor mutations in either mtDNA or nDNA coding for these proteins are
      known to lead to major and catastrophic diseases of humans, suggesting that very
      tight and precise interactions are required. To maintain the evolutionarily
      established balance after mating, monoallelic expression of the nuclear-coded
      genes would be advantageous and prevent subtly different competitive proteins
      from interacting with the resident mitochondria. This would require regulation of
      the expression of those specific nuclear genes, possibly under the control of the
      resident mitochondria. It is possible that aging cells could lose the requisite
      tight regulation and allow expression of proteins derived from the formerly
      repressed nuclear alleles that would compete for mitochondrial complex sites.
      With age, random failure of this control could lead to increasingly inefficient
      mitochondria in different tissues and organs and eventually to senescence and
      death.

PMID- 15247092
TI  - Ultrasound as an alternative to aspiration for determining the nature of pleural
      effusion, especially in older people.
AB  - Sonography was performed by two expert radiologists separately after selecting 80
      patients (45 men and 35 women) whose pleural fluids had been aspirated and
      examined by the lab. The radiologists were given no clinical information
      concerning the patients, and the result compared with lab results. The
      radiologists evaluated three criteria in determining the nature of the pleural
      effusion: septation, echogenicity, and thickening of pleura by more than 3 mm.
      The study showed that the pleural effusion with septation or internal
      echogenicity is always an exudate. Also sonographic evidence of thickened pleura
      (more than 3 mm) is highly suggestive of an exudate. Although an anechoic
      effusion is more probably evidence of a transudate, we have seen it in 14% of
      patients with exudates. The lab results showed that there were 29 patients with
      transudates and 51 with exudates, and in ultrasound results there were 34 with
      transudates and 46 with exudates. A transudate is always without echogenicity,
      while exudates can be with or without echogenicity. It was therefore concluded
      that sonography is useful in determining the nature of pleural effusion.

PMID- 15247093
TI  - Conserved network motifs allow protein-protein interaction prediction.
AB  - MOTIVATION: High-throughput protein interaction detection methods are strongly
      affected by false positive and false negative results. Focused experiments are
      needed to complement the large-scale methods by validating previously detected
      interactions but it is often difficult to decide which proteins to probe as
      interaction partners. Developing reliable computational methods assisting this
      decision process is a pressing need in bioinformatics. RESULTS: We show that we
      can use the conserved properties of the protein network to identify and validate
      interaction candidates. We apply a number of machine learning algorithms to the
      protein connectivity information and achieve a surprisingly good overall
      performance in predicting interacting proteins. Using a 'leave-one-out' approach
      we find average success rates between 20 and 40% for predicting the correct
      interaction partner of a protein. We demonstrate that the success of these
      methods is based on the presence of conserved interaction motifs within the
      network. AVAILABILITY: A reference implementation and a table with candidate
      interacting partners for each yeast protein are available at
      http://www.protsuggest.org.

PMID- 15247094
TI  - DNMAD: web-based diagnosis and normalization for microarray data.
AB  - SUMMARY: We present a web server for Diagnosis and Normalization of MicroArray
      Data (DNMAD). DNMAD includes several common data transformations such as spatial
      and global robust local regression or multiple slide normalization, and allows
      for detecting several kinds of errors that result from the manipulation and the
      image analysis of the arrays. This tool offers a user-friendly interface, and is
      completely integrated within the Gene Expression Pattern Analysis Suite (GEPAS).
      AVAILABILITY: The tool is accessible on-line at http://dnmad.bioinfo.cnio.es.

PMID- 15247095
TI  - VisRD--visual recombination detection.
AB  - SUMMARY: VisRD, a program for visual recombination detection in a sequence
      alignment is presented. VisRD is written in Java and is designed to complement
      the multi-purpose phylogenetic software package SplitsTree4. AVAILABILITY: The
      software is freely available from http://www.lcb.uu.se/~vmoulton/software/visrd/

PMID- 15247096
TI  - PLPMDB: pyridoxal-5'-phosphate dependent enzymes mutants database.
AB  - SUMMARY: The searchable mutant database PLPMDB has been developed to provide
      rapid and simple access to relevant mutant information on pyridoxal-5'-phosphate
      dependent enzymes. All data have been extracted from publications and publicly
      available databases, then organized in a relational database to enable searching
      via a web-based search form. The current version of PLPMDB contains 688 mutants
      described in 220 research papers. The database is a useful tool for planning
      mutant experiments and for interpretation of information from such experiments.
      AVAILABILITY: PLPMDB is freely accessible from
      http://www.studiofmp.com/plpmdb/index.htm.

PMID- 15247097
TI  - CSB.DB: a comprehensive systems-biology database.
AB  - SUMMARY: The open access comprehensive systems-biology database (CSB.DB) presents
      the results of bio-statistical analyses on gene expression data in association
      with additional biochemical and physiological knowledge. The main aim of this
      database platform is to provide tools that support insight into life's complexity
      pyramid with a special focus on the integration of data from transcript and
      metabolite profiling experiments. The central part of CSB.DB, which we describe
      in this applications note, is a set of co-response databases that currently focus
      on the three key model organisms, Escherichia coli, Saccharomyces cerevisiae and
      Arabidopsis thaliana. CSB.DB gives easy access to the results of large-scale co
      response analyses, which are currently based exclusively on the publicly
      available compendia of transcript profiles. By scanning for the best co-responses
      among changing transcript levels, CSB.DB allows to infer hypotheses on the
      functional interaction of genes. These hypotheses are novel and not accessible
      through analysis of sequence homology. The database enables the search for pairs
      of genes and larger units of genes, which are under common transcriptional
      control. In addition, statistical tools are offered to the user, which allow
      validation and comparison of those co-responses that were discovered by gene
      queries performed on the currently available set of pre-selectable datasets.
      AVAILABILITY: All co-response databases can be accessed through the CSB.DB Web
      server (http://csbdb.mpimp-golm.mpg.de/).

PMID- 15247098
TI  - DAGchainer: a tool for mining segmental genome duplications and synteny.
AB  - SUMMARY: Given the positions of protein-coding genes along genomic sequence and
      probability values for protein alignments between genes, DAGchainer identifies
      chains of gene pairs sharing conserved order between genomic regions, by
      identifying paths through a directed acyclic graph (DAG). These chains of
      collinear gene pairs can represent segmentally duplicated regions and genes
      within a single genome or syntenic regions between related genomes. Automated
      mining of the Arabidopsis genome for segmental duplications illustrates the use
      of DAGchainer.

PMID- 15247099
TI  - SARGE: a tool for creation of putative genetic networks.
AB  - SUMMARY: SARGE is a tool for creating, visualizing and manipulating a putative
      genetic network from time series microarray data. The tool assigns potential
      edges through time-lagged correlation, incorporates a clustering mechanism, an
      interactive visual graph representation and employs simulated annealing for
      network optimization. AVAILABILITY: The application is available as a .jar file
      from http://www.bioinformatics.cs.ncl.ac.uk/sarge/index.html.

PMID- 15247100
TI  - A computational search for box C/D snoRNA genes in the Drosophila melanogaster
      genome.
AB  - MOTIVATION: In eukaryotes, the family of non-coding RNA genes includes a number
      of genes encoding small nucleolar RNAs (mainly C/D and H/ACA snoRNAs), which act
      as guides in the maturation or post-transcriptional modifications of target RNA
      molecules. Since in Drosophila melanogaster (Dm) only few examples of snoRNAs
      have been identified so far by cDNA libraries screening, integration of the
      molecular data with in silico identification of these types of genes could throw
      light on their organization in the Dm genome. RESULTS: We have performed a
      computational screening of the Dm genome for C/D snoRNA genes, followed by
      experimental validation of the putative candidates. Few of the 26 confirmed
      snoRNAs had been recognized by cDNA library analysis. Organization of the Dm
      genome was also found to be more variegated than previously suspected, with
      snoRNA genes nested in both the introns and exons of protein-coding genes. This
      finding suggests that the presence of additional mechanisms of snoRNA biogenesis
      based on the alternative production of overlapping mRNA/snoRNA molecules.
      AVAILABILITY: Additional information is available at
      http://www.bioinformatica.unito.it/bioinformatics/snoRNAs.

PMID- 15247101
TI  - DNA structure constraint is probably a fundamental factor inducing CpG deficiency
      in bacteria.
AB  - MOTIVATION: It has been speculated that CpG dinucleotide deficiency in genomes is
      a consequence of DNA methylation. However, this hypothesis does not adequately
      explain CpG deficiency in bacteria. The hypothesis based on DNA structure
      constraint as an alternative explanation was therefore examined. RESULTS: By
      comparing real bacterial genomes and Markov artificial genomes in the second
      order, we found that the core structure of a restricted pattern, the TTCGAA
      pattern, was under represented in low GC content bacterial genomes regardless of
      CpG dinucleotide level. This is in contrast to the AACGTT pattern, indicating
      that the counterselection is context-dependent. Further study discovered nine
      underrepresented patterns that were supposed to be capable of inducing DNA
      structure constraint. In summary, most of them are in TTCGNA and TTCGAN patterns
      in both DNA strands. An explanation is also proposed for the strong correlation
      between GC content and CpG deficiency. The result of random sequence simulation
      showed that the occurrences of these patterns were correlated with GC content, as
      well as the percentage of CpG dinucleotides being trapped in these patterns.
      Finally, we suggest that the degree of counter-selection against these restricted
      patterns could be influenced by global GC content of a genome.

PMID- 15247102
TI  - MyWEST: my Web Extraction Software Tool for effective mining of annotations from
      web-based databanks.
AB  - MOTIVATION: High-throughput technologies create the necessity to mine large
      amounts of gene annotations from diverse databanks, and to integrate the
      resulting data. Most databanks can be interrogated only via Web, for a single
      gene at a time, and query results are generally available only in the HTML
      format. Although some databanks provide batch retrieval of data via FTP, this
      requires expertise and resources for locally reimplementing the databank.
      RESULTS: We developed MyWEST, a tool aimed at researchers without extensive
      informatics skills or resources, which exploits user-defined templates to easily
      mine selected annotations from different Web-interfaced databanks, and aggregates
      and structures results in an automatically updated database. Using microarray
      results from a model system of retinoic acid-induced differentiation, MyWEST
      effectively gathered relevant annotations from various biomolecular databanks,
      highlighted significant biological characteristics and supported a global
      approach to the understanding of complex cellular mechanisms. AVAILABILITY:
      MyWEST is freely available for non-profit use at
      http://www.medinfopoli.polimi.it/MyWEST/

PMID- 15247103
TI  - Effects of pooling mRNA in microarray class comparisons.
AB  - MOTIVATION: In microarray experiments investigators sometimes wish to pool RNA
      samples before labeling and hybridization due to insufficient RNA from each
      individual sample or to reduce the number of arrays for the purpose of saving
      cost. The basic assumption of pooling is that the expression of an mRNA molecule
      in the pool is close to the average expression from individual samples. Recently,
      a method for studying the effect of pooling mRNA on statistical power in
      detecting differentially expressed genes between classes has been proposed, but
      the different sources of variation arising in microarray experiments were not
      distinguished. Another paper recently did take different sources of variation
      into account, but did not address power and sample size for class comparison. In
      this paper, we study the implication of pooling in detecting differential gene
      expression taking into account different sources of variation and check the basic
      assumption of pooling using data from both the cDNA and Affymetrix GeneChip
      microarray experiments. RESULTS: We present formulas for the required number of
      subjects and arrays to achieve a desired power at a specified significance level.
      We show that due to the loss of degrees of freedom for a pooled design, a large
      increase in the number of subjects may be required to achieve a power comparable
      to that of a non-pooled design. The added expense of additional samples for the
      pooled design may outweigh the benefit of saving on microarray cost. The
      microarray data from both platforms show that the major assumption of pooling may
      not hold. SUPPLEMENTARY INFORMATION: Supplementary material referenced in the
      text is available at http://linus.nci.nih.gov/brb/TechReport.htm.

PMID- 15247104
TI  - Accuracy improvement for identifying translation initiation sites in microbial
      genomes.
AB  - MOTIVATION: At present the computational gene identification methods in microbial
      genomes have a high prediction accuracy of verified translation termination site
      (3' end), but a much lower accuracy of the translation initiation site (TIS, 5'
      end). The latter is important to the analysis and the understanding of the
      putative protein of a gene and the regulatory machinery of the translation.
      Improving the accuracy of prediction of TIS is one of the remaining open
      problems. RESULTS: In this paper, we develop a four-component statistical model
      to describe the TIS of prokaryotic genes. The model incorporates several features
      with biological meanings, including the correlation between translation
      termination site and TIS of genes, the sequence content around the start codon;
      the sequence content of the consensus signal related to ribosomal binding sites
      (RBSs), and the correlation between TIS and the upstream consensus signal. An
      entirely non-supervised training system is constructed, which takes as input a
      set of annotated coding open reading frames (ORFs) by any gene finder, and gives
      as output a set of organism-specific parameters (without any prior knowledge or
      empirical constants and formulas). The novel algorithm is tested on a set of
      reliable datasets of genes from Escherichia coli and Bacillus subtillis. MED
      Start may correctly predict 95.4% of the start sites of 195 experimentally
      confirmed E.coli genes, 96.6% of 58 reliable B.subtillis genes. Moreover, the
      test results indicate that the algorithm gives higher accuracy for more reliable
      datasets, and is robust to the variation of gene length. MED-Start may be used as
      a postprocessor for a gene finder. After processing by our program, the
      improvement of gene start prediction of gene finder system is remarkable, e.g.
      the accuracy of TIS predicted by MED 1.0 increases from 61.7 to 91.5% for 854
      E.coli verified genes, while that by GLIMMER 2.02 increases from 63.2 to 92.0%
      for the same dataset. These results show that our algorithm is one of the most
      accurate methods to identify TIS of prokaryotic genomes. AVAILABILITY: The
      program MED-Start can be accessed through the website of CTB at Peking
      University: http://ctb.pku.edu.cn/main/SheGroup/MED_Start.htm.

PMID- 15247105
TI  - A model-based optimization framework for the inference on gene regulatory
      networks from DNA array data.
AB  - MOTIVATION: Identification of the regulatory structures in genetic networks and
      the formulation of mechanistic models in the form of wiring diagrams is one of
      the significant objectives of expression profiling using DNA microarray
      technologies and it requires the development and application of identification
      frameworks. RESULTS: We have developed a novel optimization framework for
      identifying regulation in a genetic network using the S-system modeling
      formalism. We show that balance equations on both mRNA and protein species led to
      a formulation suitable for analyzing DNA-microarray data whereby protein
      concentrations have been eliminated and only mRNA relative concentrations are
      retained. Using this formulation, we examined if it is possible to infer a set of
      possible genetic regulatory networks consistent with observed mRNA expression
      patterns. Two origins of changes in mRNA expression patterns were considered. One
      derives from changes in the biophysical properties of the system that alter the
      molecular-interaction kinetics and/or message stability. The second is due to
      gene knock-outs. We reduced the identification problem to an optimization problem
      (of the so-called mixed-integer non-linear programming class) and we developed an
      algorithmic procedure for solving this optimization problem. Using simulated data
      generated by our mathematical model, we show that our method can actually find
      the regulatory network from which the data were generated. We also show that the
      number of possible alternate genetic regulatory networks depends on the size of
      the dataset (i.e. number of experiments), but this dependence is different for
      each of the two types of problems considered, and that a unique solution requires
      fewer datasets than previously estimated in the literature. This is the first
      method that also allows the identification of every possible regulatory network
      that could explain the data, when the number of experiments does not allow
      identification of unique regulatory structure.

PMID- 15247106
TI  - Quantitative DNA methylation analysis based on four-dye trace data from direct
      sequencing of PCR amplificates.
AB  - MOTIVATION: Methylation of cytosines in DNA plays an important role in the
      regulation of gene expression, and the analysis of methylation patterns is
      fundamental for the understanding of cell differentiation, aging processes,
      diseases and cancer development. Such analysis has been limited, because
      technologies for detailed and efficient high-throughput studies have not been
      available. We have developed a novel quantitative methylation analysis algorithm
      and workflow based on direct DNA sequencing of PCR products from bisulfite
      treated DNA with high-throughput sequencing machines. This technology is a
      prerequisite for success of the Human Epigenome Project, the first large genome
      wide sequencing study for DNA methylation in many different tissues. Methylation
      in tissue samples which are compositions of different cells is a quantitative
      information represented by cytosine/thymine proportions after bisulfite
      conversion of unmethylated cytosines to uracil and PCR. Calculation of
      quantitative methylation information from base proportions represented by
      different dye signals in four-dye sequencing trace files needs a specific
      algorithm handling imbalanced and overscaled signals, incomplete conversion,
      quality problems and basecaller artifacts. RESULTS: The algorithm we developed
      has several key properties: it analyzes trace files from PCR products of
      bisulfite-treated DNA sequenced directly on ABI machines; it yields quantitative
      methylation measurements for individual cytosine positions after alignment with
      genomic reference sequences, signal normalization and estimation of effectiveness
      of bisulfite treatment; it works in a fully automated pipeline including data
      quality monitoring; it is efficient and avoids the usual cost of multiple
      sequencing runs on subclones to estimate DNA methylation. The power of our new
      algorithm is demonstrated with data from two test systems based on mixtures with
      known base compositions and defined methylation. In addition, the applicability
      is proven by identifying CpGs that are differentially methylated in real tissue
      samples.

PMID- 15247107
TI  - The open lung concept: effects on right ventricular afterload after cardiac
      surgery.
AB  - BACKGROUND: The open lung concept (OLC) is a method of ventilation intended to
      maintain end-expiratory lung volume by increased airway pressure. Since this
      could increase right ventricular afterload, we studied the effect of this method
      on right ventricular afterload in patients after cardiac surgery. METHODS: We
      studied 24 stable patients after coronary artery surgery and/or valve surgery
      with cardiopulmonary bypass. Patients were randomly assigned to OLC or
      conventional mechanical ventilation (CMV). In the OLC group, recruitment
      manoeuvres were applied until Pa(o(2))/FI(O(2)) was greater than 50 kPa
      (reflecting an open lung). This value was maintained by sufficient positive
      airway pressure. In the CMV group, volume-controlled ventilation was used with a
      PEEP of 5 cm H(2)O. Cardiac index, right ventricular preload, contractility and
      afterload were measured with a pulmonary artery thermodilution catheter during
      the 3-h observation period. Blood gases were monitored continuously. RESULTS: To
      achieve Pa(O(2))/Fl(O(2)) > 50 kPa, 5.3 (3) (mean, SD) recruitment attempts were
      performed with a peak pressure of 45.5 (2) cm H(2)O. To keep the lung open, PEEP
      of 17.0 (3) cm H(2)O was required. Compared with baseline, pulmonary vascular
      resistance and right ventricular ejection fraction did not change significantly
      during the observation period in either group. CONCLUSION: No evidence was found
      that ventilation according to the OLC affects right ventricular afterload.

PMID- 15247108
TI  - Comparative effects of thiopental and propofol on atrial vulnerability:
      electrophysiological study in a porcine model including acute alcoholic
      intoxication.
AB  - BACKGROUND: Atrial tachyarrhythmias (AT) frequently complicate the perioperative
      period. Alcohol intoxication is a recognized causative factor for dysrrhythmias.
      We studied the effects of propofol and thiopental on atrial electrophysiology and
      vulnerability to AT in a closed-chest porcine model in which AT are facilitated
      by ethanol. METHODS: Thirty-eight pigs were randomly assigned to thiopental (T
      group, n=19) or propofol (P-group n=19). All animals were assigned to undergo a
      right atrial electrical stimulation protocol (RASP) at baseline. Thirty pigs were
      assigned to undergo additional RASP during ethanol infusion, while the remaining
      eight were assigned to undergo additional RASP during saline infusion (control
      group). We analysed effective refractory period (ERP), and intra-atrial
      conduction interval (ICI) (between atrial sites 4 cm apart), at several cycle
      lengths (CL). RESULTS: There were no significant differences at baseline. During
      ethanol infusion, propofol produced a greater rate-dependent decrease in
      excitability, manifested by a longer minimum paced CL with 1:1 atrial capture:
      145 (11) vs 164 (27) ms in the T- and P-group, respectively (P=0.01). Propofol
      was associated with a greater rate-related slowing in conduction: difference
      between ICI at CL of 300 ms and ICI at minimum CL: 30 ms in P-group and 22 ms in
      T-group (P<0.03). In the P-group we observed a longer duration of induced
      arrhythmias (145 (131) vs 74 (91) s, P<0.03) and a higher proportion with atrial
      flutter (AFl) (76 vs 19%, P<0.001). CONCLUSIONS: Propofol in this model was more
      arrhythmogenic than thiopental, as manifested by a longer duration of induced
      arrhythmias, particularly AFI.

PMID- 15247109
TI  - Effect of pre-emptive ketamine on sensory changes and postoperative pain after
      thoracotomy: comparison of epidural and intramuscular routes.
AB  - BACKGROUND: In this study we have evaluated the efficacy of ketamine via i.m. and
      epidural routes for the control of post-thoracotomy pain. METHODS: The study was
      randomized, double blinded and placebo controlled. With the approval of the
      Faculty Ethics Committee, 60 patients undergoing elective thoracotomy were
      randomized into three equal groups. Group IM had i.m. ketamine 1 mg kg(-1) in 2
      ml plus epidural normal saline; Group EPI had epidural ketamine 1 mg kg(-1) in 10
      ml plus i.m. normal saline; Group C had epidural normal saline 10 ml plus i.m.
      normal saline 10 ml. Anaesthesia was standardized. Postoperative analgesia was
      maintained with epidural patient-controlled analgesia using bupivacaine and
      morphine. Visual analogue scale values and analgesic consumption were evaluated
      at 2, 4, 6, 8, 10, 12, 24 and 48 h after surgery. The areas of allodynia, pin
      prick hyperalgesia and pressure hyperalgesia were measured at 48 h, and days 15
      and 30 in all groups. RESULTS: Intraoperative fentanyl requirement was
      significantly lower in Group EPI than Group C. The morphine and bupivacaine
      requirements were significantly lower in Group EPI than the other two groups in
      the postoperative period. There was reduced pin-prick hyperalgesia and touch
      allodynia in the EPI group. There were no side-effects attributable to ketamine.
      CONCLUSION: The results of the present study demonstrate that pre-emptive
      epidural ketamine is effective in reducing intra- and postoperative analgesic
      requirements, hyperalgesia and touch allodynia.

PMID- 15247110
TI  - Chronobiology of labour pain perception: an observational study.
AB  - BACKGROUND: Circadian variation may affect many biological and pharmacological
      phenomena. METHODS: To assess circadian variations in labour pain perception, 222
      consecutive nulliparous women with uncomplicated pregnancy, spontaneous labour,
      cervical dilatation (3-5 cm), ruptured membranes and normal fetal heart rate
      tracings were studied. Visual analogue pain scores (VAPS) were analysed and
      divided into four periods: night (1:01 a.m. to 7:00 a.m.), morning (7:01 a.m. to
      1:00 p.m.), afternoon (1:01 p.m. to 7:00 p.m.) and evening (7:01 p.m. to 1:00
      a.m.). VAPS were also compared between daytime (morning+afternoon) and nocturnal
      (evening+night) periods. RESULTS: Daytime mean VAPS were lower than nocturnal
      scores [75.6 (15.1) vs 85.7 (14.1), P<0.0001]. VAPS were lower in the morning
      than in the afternoon, evening and night periods (anova, P<0.0001). CONCLUSION:
      Labour pain perception appears to be chronobiological, and this might be taken
      into account when enrolling parturients in studies designed to assess or treat
      labour pain.

PMID- 15247111
TI  - Epidural infusion or combined femoral and sciatic nerve blocks as perioperative
      analgesia for knee arthroplasty.
AB  - BACKGROUND: Peripheral neural blockade appears to provide effective analgesia
      with potentially less morbidity than central neuraxial techniques. We compared
      the relative benefits of combined femoral (3-in-1) and sciatic nerve block with
      epidural blockade for postoperative knee arthroplasty analgesia. METHODS: Sixty
      patients, ASA I-III, undergoing unilateral knee replacement were prospectively
      randomized to receive either a lumbar epidural infusion or combined single-shot
      femoral (3-in-1) and sciatic blocks (combined blocks). All patients received
      standard general anaesthesia. Visual analogue pain scores and rescue opioid
      requirements were recorded at four time points postoperatively. Patient
      satisfaction, morbidity, block insertion time, perioperative blood loss and
      rehabilitation indices were also assessed. RESULTS: In both groups, pain on
      movement was well controlled at discharge from recovery and 6 h postoperatively
      but increased at 24 and 48 h. Median (95% CI) analogue scale scores were 0 (0-0),
      15 (0-30), 55 (38-75) and 54 (30-67) mm for epidural block and 0.5 (0-22), 21.5
      (10-28), 40 (20-50) and 34.5 (21-55) mm for combined block. VAS pain scores with
      the combined blocks were significantly lower at 24 h (P=0.004). Total morphine
      usage was low in both groups: median epidural group 17 mg (8-32) versus combined
      blocks 13 mg (7.8-27.5). Patient satisfaction was high in both groups with median
      (95% CI) scores of 100 (85-100), 83 (70-100) and 82 (57-90) mm for epidural and
      90 (73-100), 100 (77-100) and 97 (80-100) mm for combined blocks (not
      significant). Perioperative blood loss and rehabilitation indices were also
      similar. CONCLUSIONS: Combined femoral (3-in-1) and sciatic blocks offer a
      practical alternative to epidural analgesia for unilateral knee replacements.

PMID- 15247112
TI  - Aspiration and the laryngeal mask airway: three cases and a review of the
      literature.
AB  - The primary limitation of the laryngeal mask airway (LMA) is that it does not
      reliably protect the lungs from regurgitated stomach content. We describe three
      cases of aspiration associated with the LMA, including the first brain injury,
      the first death, and the first associated with the intubating LMA, and review the
      20 specific case reports of aspiration associated with the LMA that we were able
      to find described in the literature.

PMID- 15247113
TI  - Audit of double-lumen endobronchial intubation.
AB  - BACKGROUND: Many technical variations are possible in the placing and management
      of a double-lumen tube (DLT). We surveyed our practice to relate these variations
      to the course of the anaesthetic. METHODS: We used a questionnaire to obtain
      details of technique in 506 consecutive double lumen intubations. The details
      were related to the incidence of secretions, tube displacement, and decreases of
      oxygen saturation (<88%) during one lung anaesthesia (OLA). RESULTS: Robertshaw
      tubes were used for 482 of the 506 intubations. During OLA there were 48
      instances of desaturation (<88%), 19 cases of upper lobe obstruction, 15 of
      carinal obstruction, 16 of isolation failure, eight of excessive secretions (none
      of whom had received an antisialogogue; P<0.01) and 12 miscellaneous events. The
      experience of the anaesthetist or use of a fibre-optic bronchoscope did not
      affect these events. Air was of no advantage as a maintenance gas. Atropine 400
      600 micro g appeared to prevent desaturation on OLA (P<0.05) but glycopyrrolate
      200 micro g did not. CONCLUSION: Most factors had little effect on the progress
      of the anaesthetic, but an antimuscarinic usefully reduced secretions, and
      atropine (but not glycopyrrolate) was associated with less desaturation during
      OLA.

PMID- 15247114
TI  - Applicability of risk scores for postoperative nausea and vomiting in adults to
      paediatric patients.
AB  - BACKGROUND: Scores to predict the occurrence of postoperative vomiting (PV) or
      nausea and vomiting (PONV) are well established in adult patients. The aim of
      this survey was to evaluate the applicability of risk scores developed and tested
      in adult patients in 983 paediatric patients (0-12 yr) undergoing various
      surgical procedures. METHOD: The predictive properties of five models were
      compared with respect to discriminating power (measured by the area under a
      receiver operating characteristic curve) and calibration (comparison of the
      predicted and the actual incidences of the disease by weighed linear regression
      analysis). RESULTS: The cumulative incidence of PV was 33.2% within 24 h. The
      discriminating power was low and insufficient in all models tested (0.56-0.65).
      Furthermore, the predicted incidences of the scores correlated only vaguely with
      the actual incidences observed. CONCLUSION: Specialized scores for children are
      required. These might use the history of PV, strabismus surgery, duration of
      anaesthesia > or =45 min, age > or =5 yr and administration of postoperative
      opioids as independent risk factors.

PMID- 15247115
TI  - Increased numbers of opioid expressing inflammatory cells do not affect intra
      articular morphine analgesia.
AB  - BACKGROUND: Both locally expressed beta-endorphin (END) and low doses of morphine
      relieve pain within inflamed knee joints. Here we examined whether enhanced
      inflammation and END expression within the synovial tissue of patients undergoing
      arthroscopic knee surgery might shift the analgesic dose-response curve of intra
      articular (i.a.) morphine. METHODS: Following IRB approval and informed consent,
      patients were randomly assigned to the following i.a. treatments at the end of
      surgery: group I (n=39), isotonic saline; group II (n=40), 1 mg morphine
      hydrochloride; group III (n=48), 2 mg morphine hydrochloride; group IV (n=39), 4
      mg morphine hydrochloride. Postoperative pain intensity was assessed by the
      visual analogue scale (VAS), by the time to first analgesic request and by the
      supplemental piritramide consumption. Synovial specimens from each patient were
      stained for the presence of inflammatory cells and END and were discriminated
      into groups with low versus high numbers of these cells. Differences between
      groups were statistically analyzed by chi(2), anova and mancova where appropiate.
      RESULTS: Patient characteristics and VAS scores did not differ between groups.
      Total postoperative piritramide consumption decreased and the time to first
      analgesic request increased significantly with increasing doses of i.a. morphine
      (P<0.05, anova and linear regression). These dose-response relationships were not
      different between patients with low versus high numbers of inflammatory and END
      containing synovial cells (P>0.05, mancova). CONCLUSIONS: The dose-response
      relationship of i.a. morphine analgesia is not shifted by enhanced inflammation
      and END expression within synovial tissue. Thus, the presence of END within
      inflamed synovial tissue does not seem to interfere with i.a. morphine analgesia.

PMID- 15247117
TI  - Cancer survivorship: unique opportunities for research.

PMID- 15247116
TI  - Relationship between nocturnal hypoxaemia, tachycardia and myocardial ischaemia
      after major abdominal surgery.
AB  - BACKGROUND: Episodic hypoxaemia, cardiac arrhythmias, and myocardial ischaemia
      may be related after major abdominal surgery. METHODS: We studied 52 patients on
      the second and third nights after major abdominal operations, using continuous
      pulse oximetry and Holter ECG. We recorded the amount of time spent with oxygen
      saturation values less than 90, 85, and 80% during the night, and noted episodes
      of hypoxaemia, tachycardia, bradycardia, and ST-segment changes. RESULTS: In 87
      study nights there were 2403 (individual range 1-229) episodes of hypoxaemia,
      3509 (individual range 1-234) episodes of tachycardia, and 265 (individual range
      1-73) episodes of ST segment deviation. Of the 52 patients, 50 had episodes of
      hypoxaemia and tachycardia, and 19 patients had one or more episodes of ST
      segment deviation. For 38% of the episodes of ST deviation, there was an episode
      of hypoxaemia at the same time and in 16% there was an episode of tachycardia. ST
      deviation was only noted in 4% of the episodes of hypoxaemia and in 1% of the
      episodes of tachycardia. CONCLUSION: Episodes of hypoxaemia and tachycardia
      frequently occur together after surgery but are rarely associated with ST
      deviation. Hypoxaemia or tachycardia is often present at the same time as ST
      deviation occurs.

PMID- 15247118
TI  - The characteristics and training of professionals in cancer prevention and
      control: a survey of theAmerican Society for Preventive Oncology.
AB  - To secure continuous stewardship in the field of cancer prevention requires in
      part training the next generation of scientists and practitioners effectively. We
      characterized members and meeting registrants of the American Society for
      Preventive Oncology and assessed their career needs using an electronic survey.
      From 380 valid email addresses, 233 respondents (61%) included 143 physicians and
      81 respondents with other doctorates. More than one third worked at cancer
      centers (36%), while others worked at schools of medicine (25%) and public health
      (17%) and other institutions and businesses (22%). Among all respondents, 52%
      reported having at least one mentor but time spent advising by mentors was
      generally low. Many were less than satisfied with the amount of mentoring
      received (44%) and 52% reported interest in matching with an American Society for
      Preventive Oncology mentor. All were interested in grantsmanship training but
      junior and senior respondents differed in their preference for other topics,
      reflecting needs that change with career advancement. Other analyses focused on
      aspects of institutional commitment, which did not differ by type of degree, even
      after age adjustment. However, by gender and degree, men were completely
      supported by institutional funds more often than women among non-medical
      doctorates [age-adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) =
      1.1-9.8] but not among physicians (age-adjusted OR = 1.3, 95% CI = 0.5-3.1). Men
      were also more often in tenure-track positions than women (age-adjusted OR = 1.9,
      95% CI = 1.1-3.3). In sum, addressing the career development needs of future
      leaders in the field by providing career and mentoring sessions at annual
      meetings may help individuals in the field and enrich the discipline overall.

PMID- 15247119
TI  - Effect of exercise on serum androgens in postmenopausal women: a 12-month
      randomized clinical trial.
AB  - Postmenopausal women with elevated circulating androgen concentrations have an
      increased risk of developing breast cancer, yet interventions to reduce androgen
      levels have not been identified. We examined the effects of a 12-month moderate
      intensity exercise intervention on serum androgens. The study was a randomized
      clinical trial in 173 sedentary, overweight (body mass index > or = 24.0 kg/m(2),
      body fat > 33%), postmenopausal women, ages 50 to 75 years, not using hormone
      therapy and living in the Seattle, WA area. The exercise intervention included
      facility-based and home-based exercise (45 minutes, 5 days per week of moderate
      intensity sports/recreational exercise). A total of 170 (98.3%) women completed
      the study, with exercisers averaging 171 minutes per week of exercise. Women in
      the exercise and control groups experienced similar, nonsignificant declines in
      most androgens. Among women who lost >2% body fat, testosterone and free
      testosterone concentrations fell by 10.1% and 12.2% between baseline and 12
      months in exercisers compared with a decrease of 1.6% and 8.0% in controls (P =
      0.02 and 0.03 compared with exercisers, respectively). Concentrations of
      testosterone and free testosterone among exercisers who lost between 0.5% and 2%
      body fat declined by 4.7% and 10.4%. In controls who lost this amount of body
      fat, concentrations of testosterone and free testosterone declined by only 2.8%
      and 4.3% (P = 0.03 and 0.01 compared with exercisers, respectively). In summary,
      given similar levels of body fat loss, women randomized to a 12-month exercise
      intervention had greater declines in testosterone and free testosterone compared
      with controls. The association between exercise and breast cancer risk may be
      partly explained by the effects of exercise on these hormones.

PMID- 15247120
TI  - A prospective study of diet and benign breast disease.
AB  - Much attention has been paid to the relation between diet and breast cancer risk.
      Because benign breast disease (BBD), particularly atypical hyperplasia (AH), is a
      marker of increased breast cancer risk, studies of diet and BBD may provide
      evidence about the effect of diet at an early stage in the process of breast
      carcinogenesis. We evaluated the relationship between fat, fiber, antioxidant and
      caffeine intake and incidence of non-proliferative BBD, proliferative BBD without
      atypia and AH in the Nurses' Health Study II. We calculated rate ratios (RR) and
      95% confidence intervals (95% CI) for each quartile of energy-adjusted intake
      using the lowest quartile as reference. There was no increase in risk of BBD with
      increasing fat intake, rather increasing vegetable fat was associated with a
      significant reduction in the rate of proliferative BBD without atypia. There was
      no significant association between any type of BBD and micronutrient intake. High
      caffeine consumption was positively associated (RR = 2.46, 95% CI 1.11-5.49 for
      the highest quartile), and use of multivitamin supplements inversely associated
      (RR = 0.57, 95% CI 0.33-0.98) with risk of AH although these analyses were based
      on small numbers. These data do not support the hypothesis that higher fat
      consumption increases risk of BBD, with or without atypia, and also provide
      little evidence for a major role of antioxidants in the development of breast
      disease. They do, however, raise the possibility that high caffeine intake may
      increase, and use of vitamin supplements may decrease risk of developing AH.

PMID- 15247121
TI  - Adherence to the AICR cancer prevention recommendations and subsequent morbidity
      and mortality in the Iowa Women's Health Study cohort.
AB  - In 1997, the American Institute for Cancer Research (AICR) published 14
      recommendations related to diet for individuals to reduce cancer incidence on a
      global basis; smoking was also discouraged. We operationalized these into nine
      recommendations that are particularly relevant to western populations in a cohort
      of 29,564 women ages 55 to 69 years at baseline in 1986 who had no history of
      cancer or heart disease. The cohort was followed through 1998 for cancer
      incidence (n = 4,379), cancer mortality (n = 1,434), cardiovascular disease (CVD)
      mortality (n = 1,124), and total mortality (n = 3,398). The median number (range)
      of recommendations followed was 4 (0-8), and 33% of the cohort had ever smoked.
      Women who followed no or one recommendation compared with six to nine
      recommendations were at an increased risk of cancer incidence [relative risk (RR)
      1.35, 95% confidence interval (CI) 1.15-1.58] and cancer mortality (RR 1.43, 95%
      CI 1.11-1.85), but there was no association with CVD mortality (RR 1.06, 95% CI
      0.78-1.43). We calculated the population attributable risk (PAR) to estimate the
      proportion of cancer incidence, cancer mortality, and CVD mortality that
      theoretically would have been avoidable if the entire cohort had never smoked,
      had followed six to nine recommendations, or had done both. The PARs for smoking
      were 11% (95% CI 10-13) for cancer incidence, 21% (95% CI 17-24) for cancer
      mortality, and 20% (95% CI 16-23) for CVD mortality. The PARs for not following
      six to nine recommendations were 22% (95% CI 12-30) for cancer incidence, 11%
      (95% CI -5 to 24) for cancer mortality, and 4% (95% CI -20 to 19) for CVD
      mortality. When smoking and the operationalized AICR recommendations were
      combined together, the PARs were 31% (95% CI 19-37) for cancer incidence, 30%
      (95% CI 15-40) for cancer mortality, and 22% (95% CI 4-36) for CVD mortality.
      These data suggest that the adherence to the AICR recommendations, independently
      and in conjunction with not smoking, is likely to have a substantial public
      health impact on reducing cancer incidence and, to a lesser degree, cancer
      mortality at the population level.

PMID- 15247122
TI  - A prospective study of body size in different periods of life and risk of
      premenopausal breast cancer.
AB  - The prevalence of obesity at all ages is increasing epidemically worldwide.
      Information on the association between premenopausal breast cancer and body size
      during childhood and teenage years is scarce. In 1991 to 1992, a prospective
      cohort study was assembled in Norway and Sweden. We included in the analysis
      presented here 99,717 premenopausal women. During the follow-up period, which
      ended in December 1999, 733 of these women developed a primary invasive breast
      cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment
      was associated with a decreased risk of premenopausal breast cancer (P for linear
      trend = 0.007). Apparent associations between perceived body shape at age 7 and
      BMI at age 18, with heavier builds at both ages seemingly being protective for
      premenopausal breast cancer risk, lost their statistical significance after
      adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with
      BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48).
      Changes in body size from age 7 or 18 to adulthood did not affect per se risk of
      premenopausal breast cancer risk. Height was related to risk, with a
      statistically significantly 30% reduced risk only in women shorter than 160 cm as
      compared with taller ones. The decreased risk of premenopausal breast cancer was
      observed in overweight and obese women without, but not in those with, a family
      history of breast cancer.

PMID- 15247123
TI  - Comparison of age-specific incidence rate patterns for different histopathologic
      types of breast carcinoma.
AB  - OBJECTIVE: The age-specific incidence rate curve for breast carcinoma overall
      increases rapidly until age 50 years, and then continues to increase at a slower
      rate for older women. In this analysis, our objective was to compare age-specific
      incidence rate patterns for different morphologic types of breast carcinoma.
      MATERIALS AND METHODS: We analyzed age-specific incidence rate curves by
      histopathologic subclassification using records from 11 standard National Cancer
      Institute's Surveillance, Epidemiology, and End Results (SEER) registries,
      diagnosed during the years 1992 to 1999. Data were examined by age <50 and > or
      /=50 years to simulate menopause. RESULTS: Age-specific incidence rate curves
      showed three dominant patterns: (1) Rates for infiltrating duct carcinoma of no
      special type (duct NST), tubular, and lobular carcinomas increased rapidly until
      age 50 years then rose more slowly. (2) Rates for medullary and inflammatory
      breast carcinomas increased rapidly until age 50 years then failed to increase.
      (3) Rates for papillary and mucinous carcinomas increased steadily at all ages.
      Rate patterns varied by estrogen receptor expression but were unaffected by SEER
      registry, race, nodal status, or grade. CONCLUSION: Age-specific incidence rates
      for breast carcinomas differed by histopathologic type. Rates that failed to
      increase after 50 years suggested that menopause had greater impact on medullary
      and inflammatory carcinomas than on duct NST, tubular, and lobular carcinomas.
      Menopause did not seem to have any effect on papillary or mucinous carcinomas as
      evidenced by steadily rising rates at all ages. Future etiologic and/or
      prevention studies should consider the impact of age-specific risk factors and/or
      exposures on different histopathologic types of breast carcinomas.

PMID- 15247124
TI  - Characterization of BRCAA1 and its novel antigen epitope identification.
AB  - Looking for novel breast cancer antigen epitopes is helpful for its treatment,
      diagnosis, and prevention. brcaa1 gene is mapped at 1q42.1-q43, its whole genome
      is 93.857 kb, including 18 exons and 17 introns. BRCAA1 protein is composed of
      1,214 amino acids with 10 glycosylate sites, and shares 37% amino acid identity
      and an identical antigen epitope with Rb binding protein 1. The novel antigen
      epitope, SSKKQKRSHK, was predicted to locate in the region 610 to 619 sites, was
      synthesized, and its antibody was fabricated. Competent inhibition analysis
      showed that SSKKQKRSHK is the shortest effective peptide. The antigen epitope was
      mapped in the cytoplasm of MCF-7 cells. Immunohistochemistry analysis showed that
      the antigen epitope exhibited positive expression in 65% (39 of 60) breast cancer
      specimens and negative expression in 60 non-cancerous tissues. Statistical
      analysis shows that its expression is closely associated with status of ER and
      PR, with sensitivity of 100% and specificity of 81%, and confidence interval of
      85.9% to 96.9%. ELISA analysis showed that the mean absorbance of sera antibody
      titers from breast cancer patients and healthy donors were 0401 +/- 0.163 SD and
      0.137 +/- 0.121 SD, respectively. Sixty-four percent breast cancer patient sera
      and 13% healthy donor sera had higher titer than mean titer of healthy donors,
      and there exists significant difference between breast cancer patients and
      healthy donors (P < 0.001). In this study, a novel breast cancer antigen epitope,
      SSKKQKRSHK, is identified. Its expression is associated with characteristics that
      are themselves associated with prognosis of breast cancer, and its sera antibody
      level may be helpful for breast cancer diagnosis.

PMID- 15247125
TI  - Minority recruitment in hereditary breast cancer research.
AB  - Although recruitment of ethnic and racial minorities in medical research has been
      evaluated in several studies, much less is known about the methods used to
      recruit these populations to participate in cancer genetics research. This report
      reviews the resources that have been used to identify and recruit ethnic and
      racial minorities to participate in hereditary breast cancer research. Overall,
      hospital-based resources were used most often to identify potential subjects, and
      active recruitment methods were used most frequently to enroll eligible subjects.
      This review suggests that there appears to be a finite number of resources and
      strategies to identify and recruit potential subjects to participate in cancer
      genetics research; however, options for improving awareness about cancer genetics
      research among ethnic and racial minorities have not been extensively evaluated.
      To study ethnic and racial minority participation in cancer genetics research,
      stronger evaluation components will need to be integrated into research methods.
      Both observational and experimental studies are needed to determine resources
      that are most effective for identifying potential subjects who are ethnic and
      racial minorities and to evaluate the effects of different recruitment strategies
      on enrollment decisions among these populations.

PMID- 15247126
TI  - Mammographic density in relation to daidzein-metabolizing phenotypes in
      overweight, postmenopausal women.
AB  - Circulating hormones are associated with mammographic density, an intermediate
      marker of breast cancer risk. Differences in circulating hormones, including
      estrone and testosterone, have been observed in premenopausal women based on
      their capacity to metabolize daidzein, an isoflavone found predominantly in
      soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal
      bacterial metabolism of daidzein. There is interindividual variability in the
      capacity to produce daidzein metabolites; individuals can be equol producers or
      non-producers and O-DMA producers or non-producers. We tested the hypothesis that
      daidzein-metabolizing phenotypes are associated with mammographic density.
      Participants were recruited from among 92 sedentary, postmenopausal women, ages
      50 to 75 years, who participated in a 1-year physical activity intervention. Pre
      intervention mammographic density was determined using a computer-assisted, gray
      scale thresholding technique. Fifty-five of these women consumed supplemental soy
      protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on
      the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA
      concentrations were measured using gas chromatography-mass spectrometry.
      Associations between daidzein-metabolizing phenotypes and percent mammographic
      density were adjusted for age, maximum adult weight, gravidity, family history of
      breast cancer, and serum follicle-stimulating hormone and free testosterone
      concentrations. Mammographic density was 39% lower in equol producers compared
      with non-producers (P = 0.04). O-DMA producers had mammographic density 69%
      greater than non-producers (P = 0.05). These results suggest that particular
      intestinal bacterial profiles are associated with postmenopausal mammographic
      density, and these associations are not entirely explained by differences in
      reproductive or anthropometric characteristics or circulating hormones.

PMID- 15247127
TI  - Insulin, macronutrient intake, and physical activity: are potential indicators of
      insulin resistance associated with mortality from breast cancer?
AB  - High levels of insulin have been associated with increased risk of breast cancer,
      and poorer survival after diagnosis. Data and sera were collected from 603 breast
      cancer patients, including information on diet and physical activity, medical
      history, family history, demographic, and reproductive risk factors. These data
      were analyzed to test the hypothesis that excess insulin and related factors are
      directly related to mortality after a diagnosis of breast cancer. The cohort was
      recruited from breast cancer patients treated at the British Columbia Cancer
      Agency between July 1991 and December 1992. Questionnaire and medical record data
      were collected at enrollment and outcomes were ascertained by linkage to the BC
      Cancer Registry after 10 years of follow-up. The primary outcome of interest was
      breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using
      Cox proportional hazards regression models to relate risk factors to outcomes,
      controlling for potential confounders, such as age and stage at diagnosis. Data
      for biological variables were analyzed as a nested case-control study due to
      limited serum volumes, with at least one survivor from the same cohort as a
      control for each breast cancer death, matched on stage and length of follow-up.
      High levels of insulin were associated with poorer survival for postmenopausal
      women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest
      to lowest tertile, P trend = 0.10], while high dietary fat intake was associated
      with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3
      18.1, comparing highest to lowest quartile). Higher dietary protein intake was
      associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2
      0.8, comparing highest to lowest quartile).

PMID- 15247128
TI  - Targeting angiogenesis for mammary cancer prevention: factors to consider in
      experimental design and analysis.
AB  - An experimental model developed to investigate premalignant stages of breast
      cancer was used to establish a rationale for designing experiments that target
      angiogenesis for cancer prevention. Blood vessels were identified via CD31
      immunostaining, and all vessels that occurred in a 50 microm wide region
      circumscribing each pathology were counted using a digital imaging technique. The
      blood vessel density associated with terminal end buds was unaffected by
      carcinogen treatment, whereas vessel density was higher in intraductal
      proliferations and ductal carcinoma in situ than in terminal end buds (P < 0.001)
      and total vascularity increased with morphologic progression. In comparison with
      intraductal proliferation or ductal carcinoma in situ, mammary carcinomas had
      higher vascular density in the tissue surrounding the cancer with a marked
      increase in the number of blood vessels <25 microm(2). These data suggest that
      antiangiogenic chemopreventive agents would inhibit cancer occurrence if
      initiated at any premalignant stage of the carcinogenic process. Because
      increased vascular density observed during premalignancy could be explained by
      the size expansion of the lesion and its encroachment on a preexisting blood
      supply, by pathology-associated vessel expansion, and/or by angiogenesis, it
      remains to be determined if antiangiogenic agents will reduce the prevalence of
      premalignant lesions or cause their accumulation by blocking conversion to
      carcinomas. Failure to recognize the patterns of vascularization that accompany
      morphologic progression could limit the success of efforts to target angiogenesis
      for cancer prevention and lead to misinformation about how agents that affect
      blood vessel formation or growth inhibit the carcinogenic process.

PMID- 15247129
TI  - Lysophospholipids are potential biomarkers of ovarian cancer.
AB  - OBJECTIVE: To determine whether lysophosphatidic acid (LPA) and other
      lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of
      ovarian cancer in a controlled setting. METHOD: Plasma samples were collected
      from ovarian cancer patients and healthy control women in Hillsborough and
      Pinellas counties, Florida, and processed at the University of South Florida H.
      Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with
      epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27)
      participated in the study. Blinded LPL analysis, including 23 individual LPL
      species, was performed at the Cleveland Clinic Foundation using an electrospray
      ionization mass spectrometry-based method. LPL levels were transmitted to
      Moffitt, where clinical data were reviewed and statistical analyses were
      performed. RESULTS: There were statistically significant differences between
      preoperative case samples (n = 45) and control samples (n = 27) in the mean
      levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1
      phosphate (S1P), and individual LPA species as well as the combination of several
      LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best
      discrimination between preoperative case samples and control samples, with 93.1%
      correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases
      with both preoperative and postoperative samples, the postoperative levels of
      several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels
      and some individual species of LPA and LPC, were significantly different from
      preoperative levels. CONCLUSION: LPA, LPI, LPC, and S1P appear useful as
      diagnostic and prognostic biomarkers of ovarian cancer.

PMID- 15247130
TI  - Glycemic index, glycemic load, and carbohydrate intake in relation to risk of
      distal colorectal adenoma in women.
AB  - Case-control studies and a cohort study have shown inconsistent associations
      between a high glycemic index or a high glycemic load and risk of colorectal
      cancer. These dietary variables have not been examined in relation to risk of
      colorectal adenoma. We thus examined the associations between dietary glycemic
      index, glycemic load, and carbohydrate intake with risk of adenoma of the distal
      colon or rectum among 34,428 US women who were initially free of cancer or
      polyps, who completed a semi-quantitative food-frequency questionnaire in 1980,
      and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704
      large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal
      adenomas) were documented during 18 years of follow-up. Dietary glycemic index,
      glycemic load, and carbohydrate intake were not related to risk of total
      colorectal adenoma after adjustment for age and established risk factors
      [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95%
      confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load =
      0.92, 95% CI 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90,
      95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations
      were found for large or small adenoma, distal colon or rectal adenoma, or across
      strata of body mass index. Our findings do not support the hypothesis that a high
      glycemic index diet, a high glycemic load diet, or high carbohydrate intake
      overall are associated with risk of colorectal adenoma.

PMID- 15247131
TI  - The effect of cruciferous and leguminous sprouts on genotoxicity, in vitro and in
      vivo.
AB  - Vegetable consumption is associated with a reduced risk of colorectal cancer,
      which is the second most common cancer after lung/breast cancer within Europe.
      Some putative protective phytochemicals are found in higher amounts in young
      sprouts than in mature plants. The effect of an extract of mixed cruciferous and
      legume sprouts on DNA damage induced by H(2)O(2) was measured in HT29 cells using
      single cell microgelelectrophoresis (comet). Significant antigenotoxic effect (P
      < or = 0.05) was observed when HT29 cells were pre-incubated with the extract
      (100 and 200 microL/mL) for 24 hours and then challenged with H(2)O(2). A
      parallel design intervention study was carried out on 10 male and 10 female
      healthy adult volunteers (mean age = 25.5 years) fed 113 g of cruciferous and
      legume sprouts daily for 14 days. The effect of the supplementation was measured
      on a range of parameters, including DNA damage in lymphocytes (comet), the
      activity of various detoxifying enzymes (glutathione S-transferase, glutathione
      peroxidase, and superoxide dismutase), antioxidant status using the ferric
      reducing ability of plasma assay, plasma antioxidants (uric acid, ascorbic acid,
      and alpha-tocopherol), blood lipids, plasma levels of lutein, and lycopene. A
      significant antigenotoxic effect against H(2)O(2)-induced DNA damage was shown in
      peripheral blood lymphocytes of volunteers who consumed the supplemented diet
      when compared with the control diet (P = 0.04). No significant induction of
      detoxifying enzymes was observed during the study, neither were plasma
      antioxidant levels or activity altered. The results support the theory that
      consumption of cruciferous vegetables is linked to a reduced risk of cancer via
      decreased damage to DNA.

PMID- 15247132
TI  - Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and
      colorectal cancer.
AB  - INTRODUCTION: Insulin, insulin-like growth factor (IGF), and IGF binding protein
      (IGFBP) are involved in cell growth and proliferation and are thought to be
      important in the etiology of colorectal cancer. We hypothesize that genetic
      polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP
      3 alter colorectal cancer risk because of their roles in the insulin-related
      signaling pathway. METHODS: Data from a population-based incident case-control
      study of 1,346 colon cancer cases and 1,544 population-based controls and 952
      rectal cancer cases and 1,205 controls were used to evaluate associations.
      Genetic polymorphisms of four genes were investigated: an IGF1 CA repeat, the
      IGFBP3 -202 A > C, the IRS1 G972R, and the IRS2 G1057D. RESULTS: Having at least
      one R allele (GR or RR) for IRS1 G972R was associated with an increased risk of
      colon cancer [odds ratio 1.4, 95% confidence interval (95% CI) 1.1-1.9]. The IRS2
      G972R heterozygote GD genotype significantly reduced risk of colon cancer (odds
      ratio 0.8, 95% CI 0.6-0.9). Neither the IGF1 nor the IGFBP3 variants was
      associated independently with colon cancer, but there was an association when
      examined with IRS1. Individuals with an IRS1 R allele and IGF1 non-192 allele
      were at a 2-fold increased risk of colon cancer (95% CI 1.2-4.4). There was a 70%
      (95% CI 1.02-2.8) increased risk of colon cancer with an IRS1 R allele and the
      IGFBP3 AC or CC genotype. The IRS2 GD genotype reduced risk of colon cancer,
      except among those with an IRS1 R allele. No significant associations were seen
      in analyses of main effects or interactions of these variants and rectal cancer
      risk. CONCLUSIONS: Both IRS1 and IRS2 variants were associated with colon cancer
      risk independently. Associations were slightly stronger when polymorphisms in
      multiple genes were evaluated in conjunction with other genes rather than
      individually. These data suggest that the insulin-related pathway may be
      important in the etiology of colon cancer but not rectal cancer.

PMID- 15247133
TI  - Subsite-specific colorectal cancer incidence rates and stage distributions among
      Asians and Pacific Islanders in the United States, 1995 to 1999.
AB  - OBJECTIVE: This study examined subsite-specific colorectal cancer incidence rates
      and stage distributions for Asians and Pacific Islanders (API) and compared the
      API data with data for Whites and African Americans. METHODS: Data included
      336,798 invasive colorectal cancer incident cases for 1995 to 1999 from 23
      population-based central cancer registries, representing about two thirds of API
      population in the United States. Age-adjusted rates, using the 2000 U.S. standard
      population, and age-specific rates and stage distributions were computed by
      anatomic subsite, race, and gender. All rates were expressed per 100,000. SEs and
      rate ratios were calculated for rate comparison. A significance level of 0.05 was
      used for all analyses. RESULTS: Overall, age-adjusted colorectal cancer incidence
      rates were significantly lower in API than in Whites and African Americans across
      anatomic subsites, particularly for proximal colon cancer in which rates were 40%
      to 50% lower in API males and females. Exception to this pattern was the
      significantly (10%) higher rectal cancer incidence rate in API males than in
      African American males. The incidence patterns by anatomic subsite within API
      differed from those of Whites and African Americans. Among API, the rate of
      rectal cancer (19.2 per 100,000) was significantly higher than the rates of
      proximal (15.2 per 100,000) and distal (17.7 per 100,000) colon cancers in males,
      with little variations in rates across anatomic subsites in females. In contrast,
      among White and African American males and females, proximal colon cancer rates
      were over 25% higher than the rates of distal colon and rectal cancers. Increases
      in age-specific rates with advancing age were more striking for proximal colon
      cancer than for distal colon and rectal cancers in Whites and African Americans,
      while age-specific rates were very similar for different subsites in API with
      parallel increases with advancing age, especially in API males. Similar to Whites
      and African Americans, in API, proximal colon cancers (32% to 35%) were also less
      likely to be diagnosed with localized stage compared with distal colon (38% to
      42%) and rectal (44% to 52%) cancers. CONCLUSION: The patterns of subsite
      specific colorectal cancer incidence in API, especially API males, differ from
      those of Whites and African Americans. Similar to Whites and African Americans,
      lower percentage of localized disease in API for proximal colon cancer than for
      distal colon and rectal cancers was also observed.

PMID- 15247134
TI  - Preliminary evaluation of DNA damage related with the smoking habit measured by
      the comet assay in whole blood cells.
AB  - The alkaline single-cell gel electrophoresis (SCGE) assay, also called the comet
      assay, is a rapid and simple method for the detection of DNA damage in individual
      cells. The objective of this study was to establish if the alkaline SCGE assay in
      whole blood cells gives similar results as the same method in isolated
      lymphocytes, because whole blood cells are simpler and more economical to use,
      specifically in human genotoxic biomonitoring. To validate the method, we first
      used mouse blood cells, because mouse is one of the most commonly used animals in
      genetic toxicology testing. Groups of seven CF1 male mice were given i.p.
      injections of relatively low doses of methyl methanesulfonate (25 mg/kg body
      weight), a direct acting genotoxic agent, or cyclophosphamide (50 mg/kg body
      weight), which requires metabolic activation. Three, 6, 8, 12, 16, 20, and 65
      hours after treatment, 5 microL of blood were collected from each animal and were
      processed for the alkaline SCGE assay. On the basis of an analysis of tail
      moment, the results showed that this assay can detect DNA damage induced by both
      kinds of alkylating mutagens. We then did a preliminary study to assess the
      status of DNA damage in a young (19 to 23 years old) healthy population of male
      smokers (n = 6) and nonsmokers (n = 6) using the comet assay in whole blood
      cells. A significant difference was observed between the two groups, showing that
      the method is able to detect DNA damage in the smoking group despite the short
      time that the volunteers had actually been smoking.

PMID- 15247135
TI  - Parental exposure to medications and hydrocarbons and ras mutations in children
      with acute lymphoblastic leukemia: a report from the Children's Oncology Group.
AB  - Ras proto-oncogene mutations have been implicated in the pathogenesis of many
      malignancies, including leukemia. While both human and animal studies have linked
      several chemical carcinogens to specific ras mutations, little data exist
      regarding the association of ras mutations with parental exposures and risk of
      childhood leukemia. Using data from a large case-control study of childhood acute
      lymphoblastic leukemia (ALL; age <15 years) conducted by the Children's Cancer
      Group, we used a case-case comparison approach to examine whether reported
      parental exposure to hydrocarbons at work or use of specific medications are
      related to ras gene mutations in the leukemia cells of children with ALL. DNA was
      extracted from archived bone marrow slides or cryopreserved marrow samples for
      837 ALL cases. We examined mutations in K-ras and N-ras genes at codons 12, 13,
      and 61 by PCR and allele-specific oligonucleotide hybridization and confirmed
      them by DNA sequencing. We interviewed mothers and, if available, fathers by
      telephone to collect exposure information. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were derived from logistic regression to examine the association
      of parental exposures with ras mutations. A total of 127 (15.2%) cases had ras
      mutations (K-ras 4.7% and N-ras 10.68%). Both maternal (OR 3.2, 95% CI 1.7-6.1)
      and paternal (OR 2.0, 95% CI 1.1-3.7) reported use of mind-altering drugs were
      associated with N-ras mutations. Paternal use of amphetamines or diet pills was
      associated with N-ras mutations (OR 4.1, 95% CI 1.1-15.0); no association was
      observed with maternal use. Maternal exposure to solvents (OR 3.1, 95% CI 1.0
      9.7) and plastic materials (OR 6.9, 95% CI 1.2-39.7) during pregnancy and plastic
      materials after pregnancy (OR 8.3, 95% CI 1.4-48.8) were related to K-ras
      mutation. Maternal ever exposure to oil and coal products before case diagnosis
      (OR 2.3, 95% CI 1.1-4.8) and during the postnatal period (OR 2.2, 95% CI 1.0-5.5)
      and paternal exposure to plastic materials before index pregnancy (OR 2.4, 95% CI
      1.1-5.1) and other hydrocarbons during the postnatal period (OR 1.8, 95% CI 1.0
      1.3) were associated with N-ras mutations. This study suggests that parental
      exposure to specific chemicals may be associated with distinct ras mutations in
      children who develop ALL.

PMID- 15247136
TI  - Number of siblings and risk of Hodgkin's lymphoma.
AB  - BACKGROUND: Epidemiologic evidence indicates that risk of Hodgkin's lymphoma (HL)
      in young adults is associated with correlates of delayed exposure to infection
      during childhood. In contrast, HL among children and older adults may be
      associated with earlier childhood infection. This study examines the associations
      of HL risk with having older or younger siblings. METHODS: We conducted a case
      control study in Sweden comparing 2,140 HL patients identified from the Swedish
      Cancer Register with 10,024 controls identified from national population
      registers. The Swedish Multi-Generation Register was used to link individuals to
      their parents and siblings. RESULTS: Among young adults ages 15 to 39 years, the
      odds ratios (OR) associated with having one, two, and three or more older
      siblings, compared with none, were 0.96 [95% confidence interval (CI), 0.82
      1.13], 0.88 (95% CI, 0.72-1.09), and 0.72 (95% CI, 0.55-0.93), respectively (P
      value for trend = 0.01). In contrast, number of older siblings was not associated
      with HL risk among children or older adults. Number of younger or total siblings,
      mother's age at birth, and father's occupation were not associated with HL at any
      age. The decreased risk of young-adult HL did not vary appreciably by age
      difference or sex of older siblings. CONCLUSIONS: Risk of HL was lower among
      young adults with multiple older but not younger siblings. Having older siblings
      is associated with earlier exposure to common childhood pathogens. Pediatric and
      older-adult HL were not associated with number of siblings, suggesting a
      different pathogenesis of disease in these age groups.

PMID- 15247137
TI  - Effect of folic Acid supplementation on the folate status of buccal mucosa and
      lymphocytes.
AB  - Folate deficiency may be associated with an increased risk of cancer at certain
      sites. There is a need to measure folate status and putative biomarkers of cancer
      risk in the same target tissue, or in surrogate tissues. A study was carried out
      to develop a method for the rapid measurement of folate in human buccal mucosa
      and lymphocytes and to evaluate the responsiveness of this measurement in both
      tissues to folic acid supplementation in healthy subjects, relative to
      conventional markers of folate status. Three hundred and twenty-three adults,
      ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty
      five subjects with red cell folate between 200 and 650 nmol/L participated in a
      randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention
      trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r =
      0.36, P < 0.01) was observed between red cell folate and plasma 5
      methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly
      associated with plasma 5-MeTHF (r = 0.28, P < 0.05) and plasma total homocysteine
      concentration (r = -0.34, P < 0.05). Buccal mucosa total folate showed no
      correlation with either red cell folate or 5-MeTHF, but was significantly
      associated with lymphocyte total folate (r = 0.35, P < 0.01). Supplementation
      elicited a significant increase in lymphocyte total folate (P < 0.01), and this
      was strongly associated with the increase in RBC total folate (P < 0.01) and
      plasma 5-MeTHF (P < 0.01). Buccal mucosa total folate was not influenced by
      folate supplementation. Methods have been developed for the rapid measurement of
      lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to
      folate intake and is reflected by plasma 5-MeTHF.

PMID- 15247138
TI  - Irreversible ototoxicity associated with difluoromethylornithine.
AB  - Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine
      decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that
      promote cellular proliferation. DFMO has been tested as a potential cancer
      therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss
      is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m(2)/d,
      and generally when the cumulative dose exceeds 250 g/m(2). In a recently
      completed Barrett's esophagus chemoprevention trial, a participant developed a 15
      dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right
      ear and a > or =20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear
      after taking 0.5 g/m(2)/d DFMO for approximately 13 weeks (cumulative dose of 45
      g/m(2)). The threshold shifts persisted 7 months after DFMO was discontinued.
      There was no obvious impact on the participant's clinical hearing, but these
      findings were consistent with irreversible hearing loss. This is the first case
      reported of irreversible ototoxicity in a clinical trial participant receiving
      DFMO and, thus, trial participants should be made aware of this small but
      important risk.

PMID- 15247139
TI  - Familial risk for colorectal cancers are mainly due to heritable causes.
AB  - A family history is an identified risk factor for colorectal cancer (CRC).
      However, it is not known to what extent the risk is due to environmental or
      heritable genetic factors. We wanted to examine this question for familial CRC
      adenocarcinoma based on the nationwide Swedish Family-Cancer Database on 10.3
      million individuals whose invasive cancers were followed up to year 2000.
      Standardized incidence ratios (SIRs) for offspring, siblings, and spouses were
      calculated based on 5-year age, sex, period (10-year bands), area (county), and
      socioeconomic status standardized rates. A significant risk was observed in the
      parent-offspring comparison among different subsites (left-sided and right-sided
      colon, rectum, and all CRC), the SIRs ranging from 1.74 to 1.84. When husbands
      were probands, the SIR in wives was 0.92 for colon cancer (left-sided 0.67 and
      right-sided 1.07), 0.98 for rectal cancer, and 0.96 for CRC. The risks for
      husbands when wives were probands were quite similar. None of the SIRs between
      spouses were significant, indicating lack of concordance between spouses that
      resided together for a minimum of 30 years. The risks between siblings were also
      increased particularly for cancer in the right-sided colon (SIR 6.89). The effect
      of shared childhood environmental effects were probed by analyzing the risks by
      age difference between the siblings. However, the risks were independent of the
      age difference. Data among spouses and siblings consistently point to the
      importance of heritable factors in familial CRC.

PMID- 15247140
TI  - Specimen allocation in longitudinal biomarker studies: controlling subject
      specific effects by design.
AB  - It is important to understand specimen allocation factors that may impact the
      validity and reliability of results in longitudinal studies examining within
      person changes in biomarker levels. Using data from a randomized clinical trial
      of an exercise intervention in 136 postmenopausal women, we determined the effect
      of assaying the baseline and follow-up samples of some subjects in different
      batches on the intervention effect estimates for serum concentrations of estrone,
      estradiol, testosterone, androstenedione, and dehydroepiandrosterone. Twenty-five
      subjects had their baseline and 3-month follow-up samples and 50 subjects had
      their baseline and 12-month samples assayed in different batches; all other
      subjects had their baseline, 3-month, and 12-month samples assayed in the same
      batch. Subjects with split samples were reassayed with all samples in the same
      batch. We compared the estimated regression coefficient for the intervention
      effect using the split sample data with one estimated excluding the split sample
      data and one estimated replacing the split sample data with the reassayed data.
      The median percentage difference in the intervention effect estimate was 59.6%
      between using versus excluding the split sample data and 74.6% between using the
      split sample versus using the reassayed data. In general, the coefficients from
      the model including the split sample data were closer to zero and statistically
      less significant than those from the models excluding the split sample data or
      using the reassayed data. These results suggest that bias can be artificially
      introduced into intervention effect estimates of longitudinal studies if samples
      from a subject are not assayed in the same batch.

PMID- 15247141
TI  - Improved method for determination of 1-hydroxypyrene in human urine.
AB  - We have developed an improved method for the analysis of human urine for 1
      hydroxypyrene (1-HOP), an accepted biomarker of polycyclic aromatic hydrocarbon
      uptake. This method takes advantage of commercially available 96-well format
      devices, which expedite sample preparation before quantitation by HPLC with
      fluorescence detection. In addition to improved speed of analysis, which is
      critical for the application of this assay in molecular epidemiology studies, the
      method described here uses an internal standard, 1-hydroxybenz[a]anthracene,
      improved sample preparation methods, and optimized HPLC and fluorescence
      detection conditions. The resulting method for analysis of 1-HOP is sensitive
      (detection limit, 0.05 pmol/mL urine), accurate (as determined by known addition
      of 1-HOP to urine), and precise [relative SD (RSD), 4.13%]. A longitudinal study
      of 1-HOP levels in the urine of 10 nonsmokers showed considerable day-to-day
      (mean RSD, 55.1 %) and week-to-week (mean RSD, 38.2 %) intra-individual
      variation, indicating the necessity for multiple sampling in studies concerned
      with relatively small differences in polycyclic aromatic hydrocarbon exposure.

PMID- 15247142
TI  - Cruciferous vegetables and prostate cancer risk: confounding by PSA screening.

PMID- 15247143
TI  - Dual effects of IGFBP-3 on endothelial cell apoptosis and survival: involvement
      of the sphingolipid signaling pathways.
AB  - Insulin-like growth factor binding protein (IGFBP)-3 has both growth-inhibiting
      and growth-promoting effects at the cellular level. The cytotoxic action of
      several anticancer drugs is linked to increased ceramide generation through
      sphingomyelin hydrolysis or de novo biosynthesis. Herein, we investigated the
      role of IGFBP-3 on apoptosis of human umbilical vein endothelial cells (HUVEC)
      and its relationship with ceramide levels. We report that IGFBP-3 exerts dual
      effects on HUVEC, potentiating doxorubicin-induced apoptosis but enhancing
      survival in serum-starved conditions. Ceramide was increased by IGFBP-3 in the
      presence of doxorubicin and decreased when IGFBP-3 was added alone to cells
      cultured in serum-free medium. The protection exerted by the ceramide synthase
      inhibitor fumonisin B1 over doxorubicin-induced apoptosis was enhanced by IGFBP-3
      with concomitant reduction of ceramide levels. IGFBP-3 alone activated
      sphingosine kinase (SK) and increased SK1 mRNA; the SK inhibitor N,N
      dimethylsphingosine (DMS) blocked IGFBP-3 antiapoptotic effect. Moreover, IGFBP-3
      increased IGF-I mRNA and dramatically enhanced IGF-I release. IGF-I receptor (IGF
      IR) and its downstream signaling pathways Akt and ERK were phosphorylated by
      IGFBP-3, whereas inhibition of IGF-IR phosphorylation with tyrphostin AG1024
      suppressed the antiapopoptic effect of IGFBP-3. Finally, IGFBP-3 increased
      endothelial cell motility in all experimental conditions. These findings provide
      evidence that IGFBP-3 differentially regulates endothelial cell apoptosis by
      involvement of the sphingolipid signaling pathways. Moreover, the survival effect
      of IGFBP-3 seems to be mediated by the IGF-IR.

PMID- 15247144
TI  - A new type of antimicrobial protein with multiple histidines from the hard tick,
      Amblyomma hebraeum.
AB  - A novel 11 kDa antimicrobial protein, named as hebraein, and having a unique
      amino acid sequence, was purified from the hemolymph of fed female Amblyomma
      hebraeum ticks. A full-length cDNA clone encoding hebraein was isolated from a
      cDNA library made from tick synganglia. Hebraein consists of 102 amino acids,
      including 6 cysteine residues; has 9 histidines in its C-terminal domain that are
      mainly present as HX repeats; and has no significant similarity to any known
      protein. The secondary structure prediction is very clearly all alpha-helical (4
      6 helices) except for a very short extension at the C terminus. Such high alpha
      helical content is quite different from known antimicrobial proteins. Recombinant
      hebraein and a mutant lacking the histidine residues in the C-terminal domain
      were constructed and expressed. Assayed at the slightly acidic pH equivalent of
      fed female tick hemolymph, the wild-type and the histidine-rich recombinant
      hebraein had stronger antimicrobial activities than the histidine-deficient
      mutant. The pH-dependent properties of histidine-rich antimicrobial proteins may
      allow the design of agents that would function selectively in specific pH
      environments. The results from protein profiling of hemolymph, analyzed by
      surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass
      spectrometry combined with ProteinChip technology and RT-PCR analysis suggested
      that this antimicrobial protein was up-regulated by blood feeding. Our findings
      describe a new type of antimicrobial protein with multiple cysteine and histidine
      residues, and with unique secondary structure.

PMID- 15247145
TI  - Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal
      cells of ischemic myocardium.
AB  - Hypoxia-inducible factor (HIF)-1alpha and -2alpha are key regulators of the
      transcriptional response to hypoxia and pivotal in mediating the consequences of
      many disease states. In the present work, we define their temporo-spatial
      accumulation after myocardial infarction and systemic hypoxia. Rats were exposed
      to hypoxia or underwent coronary artery ligation. Immunohistochemistry was used
      for detection of HIF-1alpha and -2alpha proteins and target genes, and mRNA
      levels were determined by RNase protection. Marked nuclear accumulation of HIF
      1alpha and -2alpha occurred after both systemic hypoxia and coronary ligation in
      cardiomyocytes as well as interstitial and endothelial cells (EC) without
      pronounced changes in HIF mRNA levels. While systemic hypoxia led to widespread
      induction of HIF, expression after coronary occlusion occurred primarily at the
      border of infarcted tissue. This expression persisted for 4 wk, included
      infiltrating macrophages, and colocalized with target gene expression. Subsets of
      cells simultaneously expressed both HIF-alpha subunits, but EC more frequently
      induced HIF-2alpha. A progressive increase of HIF-2alpha but not HIF-1alpha
      occurred in areas remote from the infarct, including the interventricular septum.
      Cardiomyocytes and cardiac stromal cells exhibit a marked potential for a
      prolonged transcriptional response to ischemia mediated by HIF. The induction of
      HIF-1alpha and -2alpha appears to be complementary rather than solely redundant.

PMID- 15247146
TI  - PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation.
AB  - It is well established that peroxisome proliferator-activated receptor-gamma
      (PPARgamma) has a critical role in modulating adipocyte differentiation based on
      gain-of-function and loss-of-function experiments. However, recent gain-of
      function experiments suggest that PPARbeta may also have a role in mediating
      adipocyte differentiation. Because ligands for PPARs can activate more than one
      receptor isoform, the specific role of PPARbeta in adipocyte differentiation was
      examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids
      in response to differentiation signaling induced from standard differentiation
      medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The
      addition of the PPARbeta ligand L165041 to the standard differentiation medium
      causes enhanced adipocyte differentiation and lipid accumulation, and this effect
      is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild
      type adipocytes with the PPARgamma ligand troglitazone causes accelerated
      adipocyte differentiation and lipid accumulation, and this effect is marginally
      reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early
      and late adipocyte differentiation are consistent with the morphological and
      biochemical differences observed. Results from these studies demonstrate that in
      the absence of PPARbeta expression, adipocyte differentiation is significantly
      impaired, providing loss-of-function evidence supporting a role for this receptor
      in adipocyte differentiation. These results also demonstrate that L165041
      stimulated adipocyte differentiation and lipid accumulation is mediated by
      PPARbeta. In addition, as the ability of troglitazone to induce adipocyte
      differentiation is also impaired in PPARbeta null adipocytes, this suggests that
      both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid
      accumulation and differentiation during adipogenesis.

PMID- 15247147
TI  - Novel immunosuppressive properties of interleukin-6 in dendritic cells:
      inhibition of NF-kappaB binding activity and CCR7 expression.
AB  - Interleukin-6 (IL-6) is produced during bacterial and viral infections and by
      various malignant tumors. Here, we describe novel immunosuppressive properties of
      IL-6 in dendritic cells (DC). In the presence of GM-CSF, IL-4, and a maturation
      stimulus, IL-6 skewed monocyte differentiation into phenotypically mature but
      functionally impaired DC. In DC matured with the toll-like receptor (TLR)4
      stimulus lipopolysaccharide (LPS) or other pro-inflammatory stimuli, IL-6
      inhibited CCR7 chemokine receptor up-regulation. As demonstrated for LPS
      stimulated DC, IL-6 impaired chemotaxis to CCR7-activating chemokines required
      for recruiting DC to lymphoid tissues in vivo. Moreover, IL-6 inhibited
      production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma
      inducible protein-10 (IP-10) in DC, and DC-driven allogeneic T cell proliferation
      in mixed lymphocyte reactions. CCR7 expression was blocked at the transcriptional
      level. IL-6 led to inhibition of nuclear factor-kappaB (NF-kappaB) binding
      activity, regulating CCR7 transcription. Neutralization experiments revealed that
      autocrine IL-10 partially contributed to CCR7 suppression in IL-6-treated DC.
      Thus IL-6, a cytokine once labeled as "pro-inflammatory" can mediate
      immunosuppressive functions, which may involve induction of the classical "anti
      inflammatory" cytokine IL-10. Because IL-6 is expressed in response to various
      pro-inflammatory stimuli in vivo, this mechanism may contribute to down
      regulating the immune response initiated by pathogens, in persistent infections
      or tumors.

PMID- 15247148
TI  - Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth,
      apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway.
AB  - Vascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and
      apoptosis) are fundamental features in the pathogenesis of vascular disease. We
      investigated the role of Notch 1 and 3 receptor signaling in controlling adult
      SMC fate in vitro by establishing that hairy enhancer of split (hes-1 and -5) and
      related hrt's (hrt-1, -2, and -3) are direct downstream target genes of Notch 1
      and 3 receptors in SMC and identified an essential role for nuclear protein CBF
      1/RBP-Jk in their regulation. Constitutive expression of active Notch 1 and 3
      receptors (Notch IC) resulted in a significant up-regulation of CBF-1/RBP-Jk
      dependent promoter activity and Notch target gene expression concomitant with
      significant increases in SMC growth while concurrently inhibiting SMC apoptosis
      and migration. Moreover, inhibition of endogenous Notch mediated CBF-1/RBP-Jk
      regulated gene expression with a non-DNA binding mutant of CBF-1, a Notch IC
      deleted of its delta RAM domain and the Epstein-Barr virus encoded RPMS-1, in
      conjunction with pharmacological inhibitors of Notch IC receptor trafficking
      (brefeldin A and monensin), resulted in a significant decrease in cell growth
      while concomitantly increasing SMC apoptosis and migration. These findings
      suggest that endogenous Notch receptors and downstream target genes control
      vascular cell fate in vitro. Notch signaling, therefore, represents a novel
      therapeutic target for disease states in which changes in vascular cell fate
      occur in vivo.

PMID- 15247149
TI  - Nicotine and fibronectin expression in lung fibroblasts: implications for tobacco
      related lung tissue remodeling.
AB  - Tobacco-related lung diseases are associated with alterations in tissue
      remodeling and are characterized by increased matrix deposition. Among the matrix
      molecules found to be highly expressed in tobacco-related lung diseases is
      fibronectin, a cell adhesive glycoprotein implicated in tissue injury and repair.
      We hypothesize that nicotine, a component of tobacco, stimulates the expression
      of fibronectin in lung fibroblasts via the activation of intracellular signals
      that lead to increased fibronectin gene transcription. In support of this, we
      found that nicotine stimulated the expression of fibronectin in lung fibroblasts
      and that its stimulatory effect was associated with activation of protein kinase
      C and mitogen-activated protein kinases, increased levels of intracellular cAMP,
      and phosphorylation and DNA binding of the transcription factor CREB. Increased
      transcription of the gene was dependent on cAMP-response elements (CREs) present
      on the 5' end of its gene promoter. The stimulatory effect of nicotine on
      fibronectin expression was abolished by alpha-bungarotoxin, an inhibitor of
      alpha7 nicotinic acetylcholine receptors (alpha7 AChRs). Of note, nicotine
      increased the expression of alpha7 nAChRs on fibroblasts. Our data suggest that
      nicotine induces lung fibroblasts to produce fibronectin by stimulating alpha7
      nAChR-dependent signals that regulate the transcription of the fibronectin gene.

PMID- 15247150
TI  - Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2
      family members.
AB  - This study provides new insights into neuroprotection involving interaction of
      protein kinase C (PKC) pathway with Bcl-2 family proteins. Using a model of serum
      deprivation, we investigated the mechanism by which the anti-Parkinson/monoamine
      oxidase (MAO)-B inhibitor drug, rasagiline, exerts its neuroprotective effect in
      rat pheochromocytoma PC12 cells. Here, we report that rasagiline (0.1-10 microM)
      decreased apoptosis via multiple protection mechanisms, including the stimulation
      of PKC phosphorylation; up-regulation of PKCalpha and PKC mRNAs, induction of Bcl
      xL, Bcl-w, and brain-derived neurotrophic factor (BDNF) mRNAs; and down
      regulation of Bad and Bax mRNAs. Moreover, rasagiline inhibited the cleavage and
      activation of procaspase-3 and poly (ADP-ribose) polymerase (PARP), whereas the
      PKC inhibitor, GF109203X, reversed these actions. Similarly, rasagiline decreased
      serum-free-induced levels of the important regulator of cell death, Bad, which
      was also blocked by GF109203X, indicating the involvement of PKC in rasagiline
      induced cell survival. Furthermore, these studies have established that PKC- and
      Bcl-2-dependent neuroprotective activity of rasagiline is dependent on its
      propargyl moiety, because propargylamine had similar effects with the same
      potency.

PMID- 15247151
TI  - Transcriptional changes following restoration of SERCA2a levels in failing rat
      hearts.
AB  - Heart failure is characterized at the cellular level by impaired contractility
      and abnormal Ca2+ homeostasis. We have previously shown that restoration of a key
      enzyme that controls intracellular Ca(2+) handling, the sarcoplasmic reticulum
      Ca2+ ATPase (SERCA2a), induces functional improvement in heart failure. We used
      high-density oligonucleotide arrays to explore the effects of gene transfer of
      SERCA2a on genetic reprogramming in a model of heart failure. A total of 1,300
      transcripts were identified to be unmodified by the effect of virus alone. Of
      those, 251 transcripts were found to be up- or down-regulated upon failure. A
      total of 51 transcripts which were either up--(27) or down--(24) regulated in
      heart failure were normalized to the nonfailing levels by the restoration of
      SERCA2a by gene transfer. The microarray analysis identified new genes following
      SERCA2a restoration in heart failure, which will give us insights into their role
      in the normalization of multiple pathways within the failing cell.

PMID- 15247153
TI  - Developmental plasticity of NMDA receptor function in the retina and the
      influence of light.
AB  - Despite the early expression of NMDA receptors (NMDARs) in the retina, not much
      is known about their regulation and involvement in plasticity processes during
      retinal development and synapse formation. Here we report that NMDAR function in
      the inner retina is developmentally regulated and controlled by ambient light
      condition. A prominent down-regulation after eye opening of NMDAR function was
      observed in rat retinal ganglion cells (RGCs), which was prevented by dark
      rearing the animals for 1 month but was again induced by subsequent light
      exposure. As shown by molecular analysis of single RGCs, alterations in the
      subunit composition of NMDAR did not account for the light-dependent regulation
      of NMDAR function. Immunocytochemistry showed no differences in the NMDAR protein
      expression pattern between normal and dark-reared animals. In conclusion, our
      data clearly demonstrate that NMDAR function is modulated during periods of
      retinal plasticity independent of structural alterations in its subunit
      composition and thus different from mechanisms observed in higher visual centers.

PMID- 15247152
TI  - Ubiquitin-dependent lysosomal degradation of the HNE-modified proteins in lens
      epithelial cells.
AB  - 4-hydroxynonenal (HNE), a highly reactive lipid peroxidation product, may
      adversely modify proteins. Accumulation of HNE-modified proteins may be
      responsible for pathological lesions associated with oxidative stress. The
      objective of this work was to determine how HNE-modified proteins are removed
      from cells. The data showed that alphaB-crystallin modified by HNE was
      ubiquitinated at a faster rate than that of native alphaB-crystallin in a cell
      free system. However, its susceptibility to proteasome-dependent degradation in
      the cell-free system did not increase. When delivered into cultured lens
      epithelial cells, HNE-modified alphaB-crystallin was degraded at a faster rate
      than that of unmodified alphaB-crystallin. Inhibition of the lysosomal activity
      stabilized HNE-modified alphaB-crystallin, but inhibition of the proteasome
      activity alone had little effect. To determine if other HNE-modified proteins are
      also degraded in a ubiquitin-dependent lysosomal pathway, lens epithelial cells
      were treated with HNE and the removal of HNE-modified proteins in the cells was
      monitored. The levels of HNE-modified proteins in the cell decreased rapidly upon
      removal of HNE from the medium. Depletion of ATP or the presence of MG132, a
      proteasome/lysosome inhibitor, resulted in stabilization of HNE-modified
      proteins. However, proteasome-specific inhibitors, lactacystin-beta-lactone and
      epoxomicin, could not stabilize HNE-modified proteins in the cells. In contrast,
      chloroquine, a lysosome inhibitor, stabilized HNE-modified proteins. The
      enrichment of HNE-modified proteins in the fraction of ubiquitin conjugates
      suggests that HNE-modified proteins are preferentially ubiquitinated. Taken
      together, these findings show that HNE-modified proteins are degraded via a novel
      ubiquitin and lysosomal-dependent but proteasome-independent pathway.

PMID- 15247154
TI  - Sensitive nonradiometric method for determining thymidine kinase 1 activity.
AB  - BACKGROUND: Thymidine kinase 1 (TK1) is a cytoplasmic enzyme, produced only in
      the S-phase of proliferating cells, that has potential as a tumor marker.
      Specific determination of TK1 in serum is difficult, in part because of
      differences in the physical properties of serum TK1 compared with cytoplasmic
      TK1. METHODS: The first step in the new assay was phosphorylation of 3'-azido
      2',3'-deoxythymidine (AZT) to AZT 5'-monophosphate (AZTMP) by TK1 present in
      patient material. The AZTMP formed was measured in a competitive immunoassay with
      specific anti-AZTMP antibodies and AZTMP-labeled peroxidase. Results were
      compared with those of a TK radioenzyme assay (REA) for 78 samples from patients
      suffering from hematologic diseases. RESULTS: The detection limit was 78
      microIU/L, and within-run CVs <20% were seen for samples with TK1 down to 130
      microIU/L. Cross-determination of the mitochondrial isoenzyme TK2 activity was
      <0.1%. Between-assay imprecision (CV) was 3.5-7.4%, and the within-assay
      imprecision was 4.1-9.1%. In studies of recovery and linearity on dilution,
      measured values ranged from 84% to 115% of expected at concentrations of 0.26
      10.4 mIU/L. Results of the new assay (mIU/L) = 0.109 x TK REA (U/L) + 0.092.
      Heterophilic antibodies did not interfere in the assay. The upper 95th
      percentile, in 100 healthy individuals, was 0.94 mIU/L, and the median value was
      0.43 mIU/L. CONCLUSION: The TK1 enzyme-labeled immunoassay uses a stable
      substrate, is precise, appears to be accurate, and is resistant to interferences.
      It may provide a practical tool in the management of hematologic malignancies.

PMID- 15247155
TI  - Daily cyclic changes in the urinary excretion of 5-hydroxyindoleacetic acid in
      patients with carcinoid tumors.
AB  - BACKGROUND: Vasoactive peptides produced by neuroendocrine tumors can induce
      characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and
      wheezing). To what extent external factors provoke these symptoms and how
      excretion of 5-hydroxyindoleacetic acid (5-HIAA), the degradation product of
      serotonin, varies throughout the day remain unknown. In this study, we
      investigated whether symptoms and daily activity are related to 5-HIAA excretion
      and whether 24-h urine collection is needed. METHODS: In 26 patients with
      metastatic carcinoid (14 men and 12 women; median age, 60 years) urine was
      collected in portions of 4 or 8 h during 2 days. Patients were asked to keep a
      diary in which they noted symptoms of flushes, consistency of stools, activities,
      and food intake. RESULTS: Excretion of 5-HIAA in 24-h urine was increased in 88%
      of the patients (median, 515 micromol/24 h). Overnight-collected urine appeared
      the most representative for 24-h collection concentrations (correlation
      coefficient = 0.81). We found no clear correlation between symptoms of the
      carcinoid syndrome and degree of activity. Watery diarrhea was reported only by
      patients with strong variations in 5-HIAA excretion. One-half of the patients (n
      = 16) exhibited a high variability in urinary 5-HIAA excretion throughout the
      day, with increased concentrations most prominent in morning collections (P =
      0.0074) and lower concentrations in the evening (P = 0.0034). In the other
      patients these curves were flat. CONCLUSIONS: Cyclic changes in patients relate
      to high variability in 5-HIAA excretion. Overnight-collected urine can replace
      the 24-h urine collection, and marked variations in 5-HIAA excretion seem to be
      associated with severity of diarrhea.

PMID- 15247156
TI  - Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone
      to renin concentration determined by fully automated chemiluminescence
      immunoassays.
AB  - BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin
      activity (PAC/PRA) is the most common screening test for primary
      hyperaldosteronism (PHA), but it is not standardized among laboratories. We
      evaluated new automated assays for the simultaneous measurement of PAC and plasma
      renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers
      and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in
      EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was
      determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to
      1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1
      pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35
      to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU.
      In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(
      1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and
      6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU.
      Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the
      PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff
      of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages
      compared with the PAC/PRA screening method. The present study offers preliminary
      evidence that it may be a useful screening test for PHA. Further studies are
      required to validate these results, especially in hypertensive cohorts.

PMID- 15247157
TI  - Rapid, long-range molecular haplotyping of thiopurine S-methyltransferase (TPMT)
      *3A, *3B, and *3C.
AB  - BACKGROUND: Haplotyping is an important technique in molecular diagnostics
      because haplotypes are often more predictive for individual phenotypes than are
      the underlying single-nucleotide polymorphisms (SNPs). Until recently, methods
      for haplotyping SNPs separated by kilobase distances were laborious and not
      applicable to high-throughput screening. In the case of thiopurine S
      methyltransferase (TPMT*), differentiating among TPMT*3A, *3B, and *3C alleles is
      sometimes necessary for predictive genotyping. METHODS: The genomic region
      including the two SNPs that define TPMT*3A, *3B, and *3C alleles was amplified by
      long-range PCR. The resulting PCR product was circularized by ligation and
      haplotyped by allele-specific amplification PCR followed by product
      identification with hybridization probes. RESULTS: Critical points were the long
      range PCR conditions, including choice of buffer and primers, optimization of the
      ligation reaction, and selection of primers that allowed for strict allele
      specific amplification in the second-round PCR. Different underlying TPMT
      haplotypes could then be differentiated. Results from the haplotyping method were
      in full agreement with those from our standard real-time PCR method: TPMT*1/*3A
      (n = 20); TPMT*1/*3C (n = 4); TPMT*1/*1 (n = 6); and TPMT*3A/*3A (n = 6). One
      TPMT*1/*3A sample failed to amplify, and no whole blood was available for repeat
      DNA isolation. CONCLUSIONS: This method for rapid-cycle real-time, allele
      specific amplification PCR-assisted long-range haplotyping has general
      application for the haplotyping of distant SNPs. The procedure is simpler and
      more rapid than previous methods. With respect to TPMT, haplotyping has the
      potential to discriminate the genotypes TPMT*1/*3A (intermediate metabolizer) and
      TPMT*3B/*3C (poor metabolizer).

PMID- 15247158
TI  - Development of sensitive immunoassays for free and total human glandular
      kallikrein 2.
AB  - BACKGROUND: Free and total human kallikrein 2 (hK2) might improve the
      discrimination between prostate cancer and benign prostatic hyperplasia.
      Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific
      antigen (PSA); therefore, an hK2 assay must have a low detection limit and good
      specificity. METHODS: PSA- and hK2-specific monoclonal antibodies were used in
      solid-phase, two-site immunofluorometric assays to detect free and total hK2. The
      total hK2 assay used PSA-specific antibodies to block nonspecific signal. The
      capture antibody of the free hK2 assay did not cross-react with PSA. To determine
      the hK2 concentrations in the male bloodstream, total hK2 was measured in a
      control group consisting of 426 noncharacterized serum samples. Free and total
      hK2 were measured in plasma from 103 patients with confirmed prostate cancer.
      RESULTS: All 426 males in the control group had a total hK2 concentration above
      the detection limit of 0.0008 microg/L. The median total hK2 concentration was
      0.022 microg/L (range, 0.0015-0.37 microg/L). hK2 concentrations were 0.1-58% of
      total PSA (median, 3.6%). hK2 concentrations were similar in men 41-50 and 51-60
      years of age. The ratio of hK2 to PSA steadily decreased from 5-30% at PSA <1
      microg/L to 1-2% at higher PSA concentrations. In 103 patients with prostate
      cancer, the median hK2 concentration in plasma was 0.079 microg/L (range, 0.0015
      16.2 microg/L). The median free hK2 concentration was 0.070 (range, 0.005-12.2)
      microg/L. The proportion of free to total hK2 varied from 17% to 131% (mean,
      85%). CONCLUSIONS: The wide variation in the free-to-total hK2 ratio suggests
      that hK2 in blood plasma is not consistently in the free, noncomplexed form in
      patients with prostate cancer. The new assay is sufficiently sensitive to be used
      to study the diagnostic accuracies of free and total hK2 for prostate cancer.

PMID- 15247159
TI  - Local heating of human skin causes hyperemia without mediation by muscarinic
      cholinergic receptors or prostanoids.
AB  - Local changes in surface temperature have a powerful influence on the perfusion
      of human skin. Heating increases local skin blood flow, but the mechanisms and
      mediators of this response (thermal hyperemia response) are incompletely
      elucidated. In the present study, we examined the possible dependence of the
      thermal hyperemia response on stimulation of muscarinic cholinergic receptors and
      on production of vasodilator prostanoids. In 13 male healthy subjects aged 20-30
      yr, a temperature-controlled chamber was positioned on the volar face of one
      forearm and used to raise surface temperature from 34 to 41 degrees C. The time
      course of the resulting thermal hyperemia response was recorded with a laser
      Doppler imager. In one experiment, each of eight subjects received an intravenous
      bolus of the antimuscarinic agent glycopyrrolate (4 microg/kg) on one visit and
      saline on the other. The thermal hyperemia response was determined within the
      hour after the injections. Glycopyrrolate effectively inhibited the skin
      vasodilation induced by iontophoresis of acetylcholine but did not influence the
      thermal hyperemia response. In a second experiment, conducted in five other
      subjects, 1 g of the cyclooxygenase inhibitor aspirin administered orally totally
      abolished the vasodilation induced in the skin by anodal current but also failed
      to modify the thermal hyperemia response. The present study excludes the
      stimulation of muscarinic receptors and the production of vasodilator
      prostaglandins as essential and nonredundant mechanisms for the vasodilation
      induced by local heating in human forearm skin.

PMID- 15247160
TI  - Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Botzinger
      complex area induces abnormal breathing periods in awake goats.
AB  - In awake rats, >80% bilateral reduction of neurokinin-1 receptor (NK1R)
      expressing neurons in the pre-Botzinger complex (pre-BotzC) resulted in
      hypoventilation and an "ataxic" breathing pattern (Gray PA, Rekling JC, Bocchiaro
      CM, Feldman JL, Science 286: 1566-1568, 1999). Accordingly, the present study was
      designed to gain further insight into the role of the pre-BotzC area NK1R
      expressing neurons in the control of breathing during physiological conditions.
      Microtubules were chronically implanted bilaterally into the medulla of adult
      goats. After recovery from surgery, the neurotoxin saporin conjugated to
      substance P, specific for NK1R-expressing neurons, was bilaterally injected (50
      pM in 10 microl) into the pre-BotzC area during the awake state (n = 8). In
      unoperated goats, 34 +/- 0.01% of the pre-BotzC area neurons are immunoreactive
      for the NK1R, but, in goats after bilateral injection of SP-SAP into the pre
      BotzC area, NK1R immunoreactivity was reduced to 22.5 +/- 2.5% (29% decrease, P <
      0.01). Ten to fourteen days after the injection, the frequency of abnormal
      breathing periods was sixfold greater than before injection (107.8 +/- 21.8/h, P
      < 0.001). Fifty-six percent of these periods were breaths of varying duration and
      volume with an altered respiratory muscle activation pattern, whereas the
      remaining were rapid, complete breaths with coordinated inspiratory-expiratory
      cycles. The rate of occurrence and characteristics of abnormal breathing periods
      were not altered during a CO2 inhalation-induced hyperpnea. Pathological
      breathing patterns were eliminated during non-rapid eye movement sleep in seven
      of eight goats, but they frequently occurred on arousal from non-rapid eye
      movement sleep. We conclude that a moderate reduction in pre-BotzC NK1R
      expressing neurons results in state-dependent transient changes in respiratory
      rhythm and/or eupneic respiratory muscle activation patterns.

PMID- 15247161
TI  - Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory
      rhythm in awake goats.
AB  - In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing
      neurons in the pre-Botzinger complex (pre-BotzC) area with saporin conjugated to
      substance P results in transient disruptions of the normal pattern of eupneic
      respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic
      J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628,
      2004). Therefore, the purpose of these studies was to determine whether large or
      total lesioning in the pre-BotzC area of goats would eliminate phasic diaphragm
      activity and the eupneic breathing pattern. In awake goats that already had 29%
      bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre
      BotzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre
      BotzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/-
      10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter,
      breathing frequency declined, central apneas resulted in arterial hypoxemia
      (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately
      60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was
      followed by cardiac arrest in three airway-intact goats. However, after the peak
      tachypnea in four tracheostomized goats, mechanical ventilation was initiated to
      maintain arterial blood gases at control levels, during which there was no phasic
      diaphragm or abdominal muscle activity. When briefly removed from the ventilator
      (approximately 90 s), these goats became hypoxemic and hypercapnic. During this
      time, minimal, passive inspiratory flow resulted from phasic abdominal muscle
      activity. We estimate that 70% of the neurons within the pre-BotzC area were
      lesioned in these goats. We conclude that, in the awake state, the pre-BotzC is
      critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the
      absence of the pre-BotzC, spontaneous breathing reflects the activity of an
      expiratory rhythm generator.

PMID- 15247162
TI  - Training-induced changes in muscle CSA, muscle strength, EMG, and rate of force
      development in elderly subjects after long-term unilateral disuse.
AB  - The ability to develop muscle force rapidly may be a very important factor to
      prevent a fall and to perform other tasks of daily life. However, information is
      still lacking on the range of training-induced neuromuscular adaptations in
      elderly humans recovering from a period of disuse. Therefore, the present study
      examined the effect of three types of training regimes after unilateral prolonged
      disuse and subsequent hip-replacement surgery on maximal muscle strength, rapid
      muscle force [rate of force development (RFD)], muscle activation, and muscle
      size. Thirty-six subjects (60-86 yr) were randomized to a 12-wk rehabilitation
      program consisting of either 1) strength training (3 times/wk for 12 wk), 2)
      electrical muscle stimulation (1 h/day for 12 wk), or 3) standard rehabilitation
      (1 h/day for 12 wk). The nonoperated side did not receive any intervention and
      thereby served as a within-subject control. Thirty subjects completed the trial.
      In the strength-training group, significant increases were observed in maximal
      isometric muscle strength (24%, P < 0.01), contractile RFD (26-45%, P < 0.05),
      and contractile impulse (27-32%, P < 0.05). No significant changes were seen in
      the two other training groups or in the nontrained legs of all three groups. Mean
      electromyogram signal amplitude of vastus lateralis was larger in the strength
      training than in the standard-rehabilitation group at 5 and 12 wk (P < 0.05). In
      contrast to traditional physiotherapy and electrical stimulation, strength
      training increased muscle mass, maximal isometric strength, RFD, and muscle
      activation in elderly men and women recovering from long-term muscle disuse and
      subsequent hip surgery. The improvement in both muscle mass and neural function
      is likely to have important functional implications for elderly individuals.

PMID- 15247163
TI  - Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet.
AB  - With recent discussions in the literature regarding prophylactic use of early
      (within the first 12 h after birth), low-dose indomethacin to reduce the
      incidence and severity of intraventricular hemorrhage, knowledge pertaining to
      the cerebral hemodynamic effects of indomethacin in this age group is of
      significant interest. The cerebral circulation is known to undergo significant
      changes during the first few days of postnatal life. In the present study, we
      have investigated the hypothesis that postnatal adaptive changes influence the
      cerebral hemodynamic response to indomethacin in an age-dependent manner. Near
      infrared spectroscopy with indocyanine green was used to measure cerebral
      hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction
      fraction in 39 newborn piglets. Piglets were grouped by age and received either
      0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline
      (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of
      indomethacin-treated piglets (9 less than and 7 greater than 13 h of age),
      Doppler flow ultrasound was used to diagnose and monitor the presence and
      persistence of patent ductus arteriosus. Age was a significant factor in the
      cerebral hemodynamic response to indomethacin with piglets <13 h of age
      exhibiting delayed increases in cerebral blood flow and cerebral blood volume at
      150 min post-indomethacin infusion.

PMID- 15247164
TI  - Quantitative determination of localized tissue oxygen concentration in vivo by
      two-photon excitation phosphorescence lifetime measurements.
AB  - This study describes the use of two-photon excitation phosphorescence lifetime
      measurements for quantitative oxygen determination in vivo. Doubling the
      excitation wavelength of Pd-porphyrin from visible light to the infrared allows
      for deeper tissue penetration and a more precise and confined selection of the
      excitation volume due to the nonlinear two-photon effect. By using a focused
      laser beam from a 1,064-nm Q-switched laser, providing 10-ns pulses of 10 mJ,
      albumin-bound Pd-porphyrin was effectively excited and oxygen-dependent decay of
      phosphorescence was observed. In vitro calibration of phosphorescence lifetime
      vs. oxygen tension was performed. The obtained calibration constants were kq =
      356 Torr(-1) x s(-1) (quenching constant) and tau0 = 550 micros (lifetime at zero
      oxygen conditions) at 37 degrees C. The phosphorescence intensity showed a
      squared dependency to the excitation intensity, typical for two-photon
      excitation. In vivo demonstration of two-photon excitation phosphorescence
      lifetime measurements is shown by step-wise PO2 measurements through the cortex
      of rat kidney. It is concluded that quantitative oxygen measurements can be made,
      both in vitro and in vivo, using two-photon excitation oxygen-dependent quenching
      of phosphorescence. The use of two-photon excitation has the potential to lead to
      new applications of the phosphorescence lifetime technique, e.g., noninvasive
      oxygen scanning in tissue at high spatial resolution. To our knowledge, this is
      the first report in which two-photon excitation is used in the setting of oxygen
      dependent quenching of phosphorescence lifetime measurements.

PMID- 15247165
TI  - Effects of growth factors and receptor blockade on gastrointestinal cancer.
AB  - The advent of recombinant peptide technology offers the potential to use one or
      several peptides to treat a variety of gastrointestinal conditions. However,
      although cell culture and animal models have shown proof of concept, we are still
      at a relatively early stage in translating their use to standard clinical
      practice. Similarly, peptide and non-peptide antagonists of growth factor
      receptors show great potential as novel antichemotherapy agents. However, their
      actual place in clinical practice has yet to be established.

PMID- 15247166
TI  - A calcified caecal mass.

PMID- 15247167
TI  - Oesophageal cancer and gastro-oesophageal reflux: what is the relationship?

PMID- 15247168
TI  - T helper cell polarisation in coeliac disease: any (T-)bet ?

PMID- 15247169
TI  - East meets West: infection, nerves, and mast cells in the irritable bowel
      syndrome.

PMID- 15247170
TI  - Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux.
AB  - BACKGROUND AND AIMS: While patients with Barrett's oesophagus develop oesophageal
      adenocarcinoma more frequently than the general population, it has
      controversially been suggested that gastro-oesophageal reflux (GORD) itself is a
      more important determinant of risk. In order to assess the validity of this
      suggestion, we examined the risk of oesophageal cancer in patients with Barrett's
      and with GORD compared with the general population in a community based cohort
      study. METHODS: Cohorts of patients with Barrett's (n = 1677), oesophagitis (n =
      6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were
      selected from the General Practice Research Database. The last three cohorts were
      matched to the Barrett's cohort by general practitioner practice, age, and sex.
      Cox's regression analysis was used to calculate relative risks for oesophageal
      cancer. Standardised incidence ratio methodology was used to estimate the
      relative risks for oesophageal adenocarcinoma. RESULTS: A total of 137
      oesophageal cancers were identified, of which 94 prevalent cases were excluded.
      The hazard ratios for oesophageal cancer were 10.6 (5.1-22.0), 2.2 (0.9-5.2), and
      1.7 (0.7-4.5) in the Barrett's, oesophagitis, and reflux cohorts compared with
      the reference cohort, respectively. The corresponding relative risks for
      oesophageal adenocarcinoma were 29.8 (9.6-106), 4.5 (1.04-19.6), and 3.1 (0.6
      14.2). CONCLUSION: Barrett's oesophagus increases the risk of oesophageal cancer
      approximately 10 times and oesophageal adenocarcinoma approximately 30 times
      compared with the general population. There is only a modestly increased risk of
      oesophageal cancer in patients with reflux who have no record of Barrett's
      oesophagus. Our findings therefore do not support the suggestion that gastro
      oesophageal reflux disease itself predisposes to cancer.

PMID- 15247171
TI  - Effect of Th1 cytokines on acid secretion in pharmacologically characterised
      mouse gastric glands.
AB  - BACKGROUND AND AIMS: Acid secretion plays an important role in the ecology of
      Helicobacter species and acid secretory status heralds patterns of gastritis. The
      presence of inflammatory cells and their products, in close proximity to parietal
      cells, questions the extent of the effect of cytokines on acid secretion.
      METHODS: We adopted and extensively characterised the mouse gastric gland
      preparation and its secretory capacity, which was measured using (14)C
      aminopyrine accumulation. Subsequently, we tested the secretory properties of a
      wide range of species specific cytokines, including those associated with Th1 and
      Th2 immune responses. RESULTS: (14)C-aminopyrine accumulation in mouse gastric
      glands was shown to be a very sensitive "in vitro" method of testing classical
      secretagogues and antisecretory compounds, and provided pharmacological data on
      acid secretion in the mouse. Only two mouse cytokines, interleukin 2 and
      interferon gamma, had a direct effect on acid secretion causing dose dependent
      inhibition. CONCLUSIONS: Both cytokines belong to the Th1 type immune response
      and consequently their inhibitory effect may play a role in the hyposecretion
      seen with H pylori infection and colonisation throughout the corpus of the
      stomach that potentially can lead to gastric atrophy and subsequently, in some
      cases, cancer.

PMID- 15247172
TI  - Cytokine gene polymorphisms influence mucosal cytokine expression, gastric
      inflammation, and host specific colonisation during Helicobacter pylori
      infection.
AB  - BACKGROUND AND AIMS: Recent studies linked cytokine gene polymorphisms to H
      pylori related gastric cancer development. The current study evaluated the role
      of cytokine gene polymorphisms for mucosal cytokine expression, the gastric
      inflammatory response, and bacterial colonisation during H pylori infection.
      PATIENTS AND METHODS: In 207 H pylori infected patients with chronic gastritis,
      polymorphisms at different loci of the interleukin (IL)-10, IL-1B, IL-1 receptor
      antagonist (IL-1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes
      were genotyped by polymerase chain reaction (PCR), restriction fragment length
      polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal
      cytokine mRNA copy numbers were determined by real time quantitative PCR.
      Presence of bacterial virulence factors was investigated by cagA, vacAs1/2, and
      babA2 PCR. Biopsies were assessed with regard to the degrees of
      granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia
      (IM) and atrophic gastritis (AG). RESULTS: Proinflammatory IL-1 polymorphisms (IL
      1RN*2(+)/IL-1B-511T/-31C(+)) were associated with increased IL-1beta expression,
      more severe degrees of inflammation, and an increased prevalence of IM and AG.
      Carriers of the IL-10-1082G/-819C/-592C alleles (GCC haplotype) had higher
      mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with
      colonisation by more virulent cagA(+), vacAs1(+), and babA2(+) H pylori strains.
      The TNF-A-307(G/A) and IFN-G+874(A/T) polymorphisms did not influence mucosal
      cytokine expression or the inflammatory response to H pylori. CONCLUSIONS:
      Cytokine gene polymorphisms influence mucosal cytokine expression, gastric
      inflammation, and the long term development of precancerous lesions in H pylori
      infection. Host polymorphisms are associated with certain bacterial strain types,
      suggesting host specific colonisation or adaptation. These findings contribute to
      the understanding of the complex interplay between host and bacterial factors
      involved in the development of gastric pathology.

PMID- 15247173
TI  - Regulation of the T helper cell type 1 transcription factor T-bet in coeliac
      disease mucosa.
AB  - BACKGROUND: In coeliac disease (CD) mucosa, the histological lesion is associated
      with marked infiltration of T helper cell type 1 (Th1) cells. However, the
      molecular mechanisms which regulate Th1 cell differentiation in CD mucosa are
      unknown. AIMS: To analyse expression of transcription factors which control the
      Th1 cell commitment in CD. PATIENTS: Duodenal mucosal samples were taken from
      untreated CD patients and normal controls. METHODS: Interferon gamma (IFN-gamma)
      and interleukin (IL)-4 RNA expression was examined in T lamina propria
      lymphocytes by quantitative reverse transcription-polymerase chain reaction. T
      bet and STAT-4, two Th1 promoting transcription factors, and STAT-6 and GATA-3,
      transcription factors which govern T helper cell type 2 (Th2) cell polarisation,
      were examined in duodenal biopsies by western blotting. The effect of gliadin and
      IFN-gamma on expression of T-bet was examined in an ex vivo culture of biopsies
      taken from normal and treated CD patients. RESULTS: As expected, IFN-gamma but
      not IL-4 RNA transcripts were increased in the mucosa of CD patients in
      comparison with controls. CD mucosal samples consistently exhibited higher levels
      of T-bet than controls. However, no difference in active STAT-4 expression was
      seen between CD patients and controls, suggesting that Th1 polarisation was not
      induced by local IL-12. GATA-3 and STAT-6 were also low in both CD and control
      mucosa. In normal duodenal biopsies, IFN-gamma stimulated T-bet through a STAT-1
      dependent mechanism. Challenge of treated CD but not control biopsies with
      gliadin enhanced T-bet and this effect was also inhibited by STAT-1 inhibition.
      CONCLUSIONS: This study shows that activation of STAT-1 by IFN-gamma promotes T
      bet in CD mucosa.

PMID- 15247174
TI  - Bacillary dysentery as a causative factor of irritable bowel syndrome and its
      pathogenesis.
AB  - BACKGROUND AND AIMS: The incidence of irritable bowel syndrome (IBS) or
      functional bowel disorders (FBD) after bacillary dysentery (BD) has not been
      extensively evaluated, and little is known of the pathogenesis of post-infective
      (PI) IBS. Therefore, we investigated the incidence of IBS and FBD in a Chinese
      patient population who had recovered from BD. To further elucidate its
      pathogenesis, neuroimmunological changes, including interleukins (IL), mast
      cells, neuropeptides, and the relationship between mast cells and intestinal
      nerves, were investigated. METHODS: A cohort study of 295 patients who had
      recovered from BD (shigella identified from stool in 71.4%) and 243 control
      subjects consisting of patient siblings or spouses who had not been infected with
      BD were included in the study. All subjects were followed up using questionnaires
      for 1-2 years to explore the incidence of FBD and IBS, as defined by the Rome II
      criteria. In 56 cases of IBS (PI and non-PI) from another source, the number of
      mast cells in biopsy specimens from the intestinal mucosa were stained with
      antitryptase antibody and counted under light microscopy. Also, the relationship
      of mast cells to neurone specific enolase (NSE), substance P (SP), 5
      hydroxytryptamine (5-HT), or calcitonin gene related peptide positive nerve
      fibres was observed using double staining with alcian blue and neuropeptide
      antibodies. In 30 cases of IBS (PI-IBS, n = 15) taken at random from the 56
      cases, expression of interleukin (IL)-1alpha, IL-1beta, and IL-1 receptor
      antagonist (IL-1ra) mRNAs in intestinal mucosa were identified using reverse
      transcription-polymerase chain reaction. The above results were compared with 12
      non-IBS controls. RESULTS: In the BD infected cohort, the incidences of FBD and
      IBS were 22.4% and 8.1% (in total)-10.2% (among those in who shigella were
      identified) respectively, which were significantly higher (p<0.01) than the
      incidences of FBD (7.4%) and IBS (0.8%) in the control cohort. A longer duration
      of diarrhoea (>or=7 days) was associated with a higher risk of developing FBD
      (odds ratio 3.49 (95% confidence interval 1.71-7.13)). Expression of IL-1beta
      mRNA in terminal ileum and rectosigmoid mucosa was significantly higher in PI-IBS
      patients (p<0.01). The number of mast cells in the terminal ileum mucosa in PI
      IBS (11.19 (2.83)) and non-PI-IBS patients (10.78 (1.23)) was significantly
      increased compared with that (6.05 (0.51)) in control subjects (p<0.01). Also, in
      the terminal ileum and rectosigmoid mucosa of IBS patients, the density of NSE,
      SP, and 5-HT positively stained nerve fibres increased (p<0.05) and appeared in
      clusters, surrounding an increased number of mast cells (p<0.01 compared with
      controls). CONCLUSIONS: BD is a causative factor in PI-IBS. The immune and
      nervous system may both play important roles in the pathogenesis of PI-IBS.

PMID- 15247175
TI  - Altered visceral perceptual and neuroendocrine response in patients with
      irritable bowel syndrome during mental stress.
AB  - BACKGROUND AND AIMS: Stress often worsens the symptoms of irritable bowel
      syndrome (IBS). We hypothesised that this might be explained by altered
      neuroendocrine and visceral sensory responses to stress in IBS patients. SUBJECTS
      AND METHODS: Eighteen IBS patients and 22 control subjects were assessed using
      rectal balloon distensions before, during, and after mental stress. Ten controls
      and nine patients were studied in supplementary sessions. Rectal sensitivity
      (thresholds and intensity-visual analogue scale (VAS)) and perceived stress and
      arousal (VAS) were determined. Plasma levels of corticotropin releasing factor
      (CRF), adrenocorticotropic hormone (ACTH), cortisol, noradrenaline, and
      adrenaline were analysed at baseline, immediately after stress, and after the
      last distension. Heart rate was recorded continuously. RESULTS: Thresholds were
      increased during stress in control subjects (p<0.01) but not in IBS patients.
      Both groups showed lower thresholds after stress (p<0.05). Repeated distensions
      without stress did not affect thresholds. Both groups showed increased heart rate
      (p<0.001) and VAS ratings for stress and arousal (p<0.05) during stress. Patients
      demonstrated higher ratings for stress but lower for arousal than controls. Basal
      CRF levels were lower in patients (p<0.05) and increased significantly during
      stress in patients (p<0.01) but not in controls. Patients also responded with
      higher levels of ACTH during stress (p<0.05) and had higher basal levels of
      noradrenaline than controls (p<0.01). Controls, but not patients, showed
      increased levels of adrenaline and noradrenaline in response to stress (p<0.05).
      CONCLUSIONS: Stress induced exaggeration of the neuroendocrine response and
      visceral perceptual alterations during and after stress may explain some of the
      stress related gastrointestinal symptoms in IBS.

PMID- 15247176
TI  - Chemical nociception in the jejunum induced by capsaicin.
AB  - BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been
      studied extensively. Although capsaicin can cause intestinal sensations, it is
      not known if this is due to stimulation of chemoreceptors or to motor changes.
      Our aims were to evaluate motor activity during capsaicin induced nociception and
      to compare qualities of jejunal nociception induced by capsaicin and mechanical
      distension. METHODS: Twenty nine healthy subjects swallowed a tube with a
      perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon.
      Phasic motor activity was measured around the perfusion site and the balloon.
      Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60
      minutes or until severe discomfort occurred. A graded questionnaire for seven
      different sensations was completed every 10 minutes and after capsaicin perfusion
      was replaced by saline perfusion because of severe discomfort. Sensations arising
      from pressure controlled distensions were assessed before and after capsaicin
      perfusion when sensations had stopped (n = 19), or during capsaicin
      administration when no discomfort was reported (n = 5). RESULTS: Capsaicin
      perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and
      abdominal location of these sensations were similar to those induced by
      distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12
      subjects receiving 40 microg/ml capsaicin and all subjects receiving higher
      capsaicin concentrations developed discomfort. Perfusion had to be stopped after
      55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml
      capsaicin, respectively, whereafter the sensations disappeared within 10 minutes.
      Repeated capsaicin (200 microg/ml) applications significantly reduced the time
      until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin
      but phasic activity proximal to the perfusion site was reduced during capsaicin
      induced discomfort (p<0.001). Pain thresholds during distensions were not
      different before and after capsaicin perfusion. CONCLUSION: Despite the
      similarities in abdominal localisation and perceptional quality of capsaicin and
      distension induced sensations, our results rule out the fact that abdominal
      discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an
      increase in phasic and tonic motor activity. Capsaicin evokes abdominal
      sensations by stimulation of chemoreceptors which proves the existence of
      chemonociception in the human small intestine.

PMID- 15247177
TI  - Anti-Saccharomyces cerevisiae antibody (ASCA) positivity is associated with
      increased risk for early surgery in Crohn's disease.
AB  - BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCA) are a specific but
      only moderately sensitive diagnostic marker for Crohn's disease. We sought to
      explore the role of ASCA as a prognostic marker for aggressive disease phenotype
      in Crohn's disease. AIMS: To determine the role of ASCA status as a risk factor
      for early surgery in Crohn's disease. SUBJECTS: We performed a case control study
      in a cohort of patients, newly diagnosed with Crohn's disease, between 1991 and
      1999. All patients were followed for at least three years. Case subjects (n = 35)
      included those who had major surgery for Crohn's disease within three years of
      diagnosis. Controls (n = 35) included patients matched to cases for age, sex,
      disease location, and smoking status, and who did not undergo major surgery for
      Crohn's disease within three years of diagnosis. METHODS: Blinded assays were
      performed on serum for ASCA (immunoglobulin (Ig)A and IgG). A paired analysis of
      cases-controls was performed to test for the association between ASCA status and
      risk of early surgery. RESULTS: ASCA IgA was strongly associated with early
      surgery (odds ratio (OR) 8.5 (95% confidence interval (CI) 2.0-75.9); p =
      0.0013). ASCA IgG+ and ASCA IgG+/IgA+ patients were also at increased risk for
      early surgery (OR 5.5 (95% CI 1.2-51.1), p = 0.0265; and OR 5.0 (95% CI 1.1
      46.9), p = 0.0433, respectively). The association between ASCA and early surgery
      was evident in patients requiring surgery for ileal or ileocolonic disease.
      CONCLUSIONS: Patients with Crohn's disease who are positive for ASCA IgA, IgG, or
      both, may define a subset of patients with Crohn's disease at increased risk for
      early surgery.

PMID- 15247178
TI  - A male with a pelvic mass.

PMID- 15247179
TI  - Clinical significance of azathioprine active metabolite concentrations in
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: There are conflicting reports on the role of azathioprine
      (AZA) thioguanine nucleotide (TGN) metabolites in optimising therapy for
      inflammatory bowel disease (IBD). The aim of this study was to investigate TGN
      intrapatient variation, and the relationship between TGN concentrations and
      disease activity in IBD patients taking long term constant dose AZA. METHODS: TGN
      and methylmercaptopurine nucleotide (MeMPN) concentrations were measured at
      intervals over a two year period. Disease activity was assessed at each clinic
      visit using the Crohn's disease activity index or Walmsley simple index for
      ulcerative colitis. RESULTS: Serial TGNs were measured in 159 patients (3-14 TGN
      assays, median 6). Intrapatient variation in TGN concentrations was 1-5-fold
      (median 1.6); the incidence of non-compliance was 13%. At the end of two years,
      131 patients were evaluable at TGN steady state. Of this group, patients who
      remained in remission had significantly higher mean TGN concentrations than those
      patients who developed active disease (median TGNs 236 v 175, respectively;
      median difference 44 pmol (95% confidence interval 1-92); p = 0.04). MeMPN
      concentrations were not related to AZA efficacy or toxicity. CONCLUSIONS: This
      study has shown that lower TGN concentrations were linked to the development of
      active disease, and that TGNs may act as useful markers of compliance. However,
      it is clear that repeat TGN measurements are required for an unambiguous index of
      active metabolite exposure. In view of the high intrapatient variability in TGN
      production over time, TGN measurements may not be currently advocated for routine
      clinical use.

PMID- 15247180
TI  - Measurement of vitamin D levels in inflammatory bowel disease patients reveals a
      subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low
      bone mineral density.
AB  - OBJECTIVES: Many patients with Crohn's disease (CD) have low bone mineral density
      (BMD) that may not be solely attributable to glucocorticoid use. We hypothesised
      that low BMD in patients with CD is associated with elevated circulating levels
      of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D). We
      further hypothesised that this was secondary to increased synthesis of
      1,25(OH)(2)D by inflammatory cells in the intestine. The aim of this study was to
      examine the relationship between 1,25(OH)(2)D levels and BMD in patients with CD.
      METHODS: An IRB approved retrospective review of medical records from patients
      with CD (n = 138) or ulcerative colitis (UC, n = 29). Measurements of vitamin D
      metabolites and immunoreactive parathyroid hormone (iPTH) were carried out. BMD
      results were available for 88 CD and 20 UC patients. Immunohistochemistry or real
      time reverse transcription-polymerase chain reaction (RT-PCR) for the enzyme
      1alpha-hydroxylase was performed on colonic biopsies from patients with CD (14)
      or UC (12) and normal colons (4). RESULTS: Inappropriately high levels of serum
      1,25(OH)(2)D (>60 pg/ml) were observed in 42% of patients with CD compared with
      only 7% in UC, despite no differences in mean iPTH. Serum 1,25(OH)(2)D levels
      were higher in CD (57 pg/ml) versus UC (41 pg/ml) (p = 0.0001). In patients with
      CD, there was a negative correlation between 1,25(OH)(2)D levels and lumbar BMD
      (r = -0.301, p = 0.005) independent of therapeutic glucocorticoid use.
      1,25(OH)(2)D levels also correlated with CD activity. Lastly,
      immunohistochemistry and RT-PCR demonstrated increased expression of intestinal
      1alpha-hydroxylase in patients with CD. CONCLUSIONS: These data demonstrate that
      elevated 1,25(OH)(2)D is more common in CD than previously appreciated and is
      independently associated with low bone mineral density. The source of the active
      vitamin D may be the inflamed intestine. Treatment of the underlying inflammation
      may improve metabolic bone disease in this subgroup of patients.

PMID- 15247181
TI  - BRAF mutation is associated with DNA methylation in serrated polyps and cancers
      of the colorectum.
AB  - BACKGROUND AND AIMS: Mutations in BRAF have been linked with colorectal cancers
      (CRC) showing high level microsatellite instability (MSI-H). However, the
      distribution of BRAF mutations in MSI-H cancers remains to be clarified with
      respect to precursor lesions and the CpG island methylator phenotype (CIMP).
      METHODS: Forty three hyperplastic polyps (HP), nine mixed polyps (MP), five
      serrated adenomas (SA), 28 conventional adenomas (AD), 18 hereditary non
      polyposis colorectal cancers (HNPCC), and 127 sporadic CRC (46 MSI-H and 81 non
      MSI-H) were collected from patients undergoing colectomy for either CRC or
      hyperplastic polyposis. Twenty five of 57 serrated lesions were derived from four
      patients with hyperplastic polyposis. HP were further subdivided according to
      recently documented morphological criteria into 27 classical HP and 16 variant
      lesions described as "sessile serrated adenoma" (SSA). All tumours were screened
      for BRAF activating mutations. RESULTS: The BRAF mutation was more frequent in
      SSA (75%) and MP (89%) than in classical HP (19%), SA (20%), and AD (0%)
      (p<0.0001), and also in sporadic MSI-H cancers (76%) compared with HNPCC (0%) and
      sporadic non-MSI-H cancers (9%) (p<0.0001). The BRAF mutation was identified more
      often in CIMP-high serrated polyps (72%) and CIMP-high CRC (77%) than in CIMP-low
      (30%) and CIMP-negative (13%) polyps (p = 0.002) as well as CIMP-low (18%) and
      CIMP-negative (0%) CRC (p<0.0001). CONCLUSIONS: The BRAF mutation was frequently
      seen in SSA and in sporadic MSI-H CRC, both of which were associated with DNA
      methylation. Sporadic MSI-H cancers may originate in SSA and not adenomas, and
      BRAF mutation and DNA methylation are early events in this "serrated" pathway.

PMID- 15247183
TI  - Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in
      mice.
AB  - BACKGROUND: Glucagon-like peptide 2 (GLP-2) is an intestinotrophic mediator with
      therapeutic potential in conditions with compromised intestinal capacity.
      However, growth stimulation of the intestinal system may accelerate the growth of
      existing neoplasms in the intestine. AIMS: In the present study, the effects of
      GLP-2 treatment on the growth of chemically induced colonic neoplasms were
      investigated. METHODS: In 210 female C57bl mice, colonic tumours were initially
      induced with the methylating carcinogen 1,2-dimethylhydrazine (DMH) and mice were
      then treated with GLP-2. Two months after discontinuation of the carcinogen
      treatment, 135 of the mice were allocated to one of six groups which were treated
      twice daily with 25 microg GLP-2, 25 microg Gly2-GLP-2 (stable analogue), or
      phosphate buffered saline for a short (10 days) or long (one month) period. The
      remaining 75 mice had a treatment free period of three months and were then
      allocated to groups subjected to long term treatment, as above. RESULTS: Colonic
      polyps developed in 100% of the mice, regardless of treatment. Survival data
      revealed no statistical significant differences among the different groups but
      histopathological analysis demonstrated a clear and significant increase in
      tumour load of mice treated with Gly2-GLP-2. The tumour promoting effect of
      native GLP-2 was less pronounced but the number of small sized polyps increased
      following long term treatment. CONCLUSIONS: The present results clearly indicate
      that GLP-2 promotes the growth of mucosal neoplasms. Our findings highlight the
      need for future investigations on the effects of GLP-2 in conditions needing long
      time treatment or with increased gastrointestinal cancer susceptibility.

PMID- 15247184
TI  - An unusual case of abdominal pain.

PMID- 15247185
TI  - Downregulation of prostaglandin E receptor subtype EP3 during colon cancer
      development.
AB  - BACKGROUND AND AIMS: Involvement of prostaglandin E(2) (PGE(2)) receptors EP(1),
      EP(2), and EP(4) in the formation of aberrant crypt foci (ACF) and/or intestinal
      polyps has been suggested. In contrast, EP(3) appears to have no influence on the
      early stages of colon carcinogenesis. In the present study, we examined
      expression of PGE(2) receptor subtypes EP(1), EP(2), EP(3), and EP(4) in normal
      colon mucosa and colon cancers, and assessed the contribution of EP(3) to colon
      cancer development. METHODS: mRNA expression of PGE(2) receptor subtypes EP(1),
      EP(2), EP(3), and EP(4) in normal colon mucosa and colon cancers in azoxymethane
      (AOM) treated mice and rats, and in humans, were examined by reverse
      transcription-polymerase chain reaction (RT-PCR), quantitative real time RT-PCR,
      and immunohistochemical analyses. Evaluation of the role of EP(3) was performed
      by intraperitoneal injection of AOM, using EP(3) receptor knockout mice. Effects
      of EP(3) receptor activation on cell growth of human colon cancer cell lines were
      examined using ONO-AE-248, an EP(3) selective agonist. Moreover, EP(3) expression
      in colon cancer cell lines was analysed with or without 5-aza-2'-deoxycytidine (5
      aza-dC) treatment. RESULTS: Expression levels of EP(1) and EP(2) mRNA were
      increased in cancer tissues. EP(4) mRNA was constantly expressed in normal mucosa
      and cancers. In contrast, expression of EP(3) mRNA was markedly decreased in
      colon cancer tissues, being 5% in mice, 9% in rats, and 28% in humans compared
      with normal colon mucosa, analysed by quantitative real time RT-PCR.
      Immunohistochemical staining demonstrated the rat EP(3) receptor protein to be
      expressed in epithelial cells of normal mucosa and some parts of small carcinomas
      but hardly detectable in large carcinomas of the colon. Colon cancer development
      induced by AOM in EP(3) receptor knockout mice was enhanced compared with wild
      type mice, with a higher incidence of colon tumours (78% v 57%) and mean number
      of tumours per mouse (2.17 (0.51) v 0.75 (0.15); p<0.05). Expression of EP(3)
      mRNA was detected in only one of 11 human colon cancer cell lines tested.
      Treatment with 5 microM of an EP(3) selective agonist, ONO-AE-248, resulted in a
      30% decrease in viable cell numbers in the HCA-7 human colon cancer cell line in
      which EP(3) was expressed. Treatment with 5-aza-dC restored EP(3) expression in
      CACO-2, CW-2, and DLD-1 cells but not in WiDr cells, suggesting involvement of
      hypermethylation in the downregulation of EP(3) to some extent. CONCLUSION: The
      PGE(2) receptor subtype EP(3) plays an important role in suppression of cell
      growth and its downregulation enhances colon carcinogenesis at a later stage.
      Hypermethylation of the EP(3) receptor gene could occur and may contribute
      towards downregulating EP(3) expression to some extent in colon cancers.

PMID- 15247186
TI  - Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned
      myoblasts: searching for a gene expression pattern with a microarray analysis of
      5000 skeletal muscle genes.
AB  - BACKGROUND AND AIMS: We verified whether conditioned media (CM) from pancreatic
      cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and
      gene expression profiles (microarray experiment with a platform of 5000 skeletal
      muscle cDNA) in mice myoblasts. METHODS: Myoblasts were incubated with control or
      pancreatic cancer CM for 24 and 48 hours. RESULTS: Lactate significantly
      increased in CM compared with non-conditioned myoblasts. No variations in
      expression levels of the main genes involved in glycolysis were found in CM
      myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta
      genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed,
      while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and
      BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin
      G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM
      myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin
      alpha, troponin T1, and filamin A were underexpressed in CM myoblasts.
      CONCLUSIONS: Our findings demonstrate that pancreatic cancer cell conditioned
      media enhanced lactate production and induced proteolysis, possibly by altering
      expression levels of a large number of genes, not only those involved in protein
      biosynthesis and degradation or glucose metabolism, but also those involved in
      the tricarboxylic acid cycle and in vesicle traffic.

PMID- 15247187
TI  - Repeated adenoviral administration into the biliary tract can induce repeated
      expression of the original gene construct in rat livers without immunosuppressive
      strategies.
AB  - BACKGROUND: Systemic adenoviral readministration appears to be limited by
      immunogenicity. AIMS: We examined the feasibility of repeated adenovirus mediated
      gene transfer into the liver via the biliary tract. METHODS: Recombinant
      adenoviruses carrying a reporter lacZ gene were infused retrogradely into the
      common bile duct of rats. Transduction efficiency of the lacZ gene was estimated
      histochemically and quantitatively. RESULTS: Retrograde administration of
      recombinant adenoviruses into the common bile duct of rats resulted in efficient
      transgene expression in the liver, specifically in hepatocytes, but not in
      biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral
      administration was not substantially different from that induced by intraportal
      adenoviral infusion. Transgene expression in the liver was however transient, and
      development of neutralising antibodies against adenovirus was observed in serum
      but not in bile. When adenoviruses were readministered into the common bile duct,
      successful re-expression of the transgene in the liver was achieved despite the
      existence of neutralising antibodies in serum. Interestingly, although
      proliferation of adenovirus specific T cells in response to adenoviral
      readministration was suppressed significantly by immunosuppressive FK506
      treatment, levels of transgene expression in the liver achieved by intrabiliary
      adenoviral readministration were not significantly different between animals
      treated with and without FK506. Furthermore, third adenoviral administration into
      the common bile duct also induced successful transgene expression in the liver.
      CONCLUSIONS: These results suggest that adenovirus mediated gene transfer into
      the liver may be repeatable without immunosuppressive strategies in clinical
      settings by means of endoscopic retrograde cholangiography.

PMID- 15247188
TI  - Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in
      hereditary haemochromatosis.
AB  - BACKGROUND AND AIMS: While upregulation of divalent metal transporter 1 (DMT1)
      and iron regulated gene 1 (IREG1) within duodenal enterocytes is reported in
      patients with hereditary haemochromatosis (HH), these findings are controversial.
      Furthermore, the effect of HFE, the gene mutated in HH, on expression of these
      molecules is unclear. This study examines duodenal expression of these three
      molecules in HH patients (prior to and following phlebotomy), in patients with
      iron deficiency (ID), and in controls. METHODS: DMT1, IREG1, and HFE mRNA were
      measured in duodenal tissue of C282Y homozygous HH patients, in ID patients
      negative for the C282Y mutation with a serum ferritin concentration less than 20
      microg/l, and in controls negative for C282Y and H63D mutations with normal iron
      indices, using real time polymerase chain reaction. RESULTS: DMT1 and IREG1 mRNA
      levels were not significantly different in non-phlebotomised (untreated) HH
      patients compared with controls. DMT1 expression was significantly increased in
      HH patients who had undergone phlebotomy therapy (treated) and in patients with
      ID compared with controls. IREG1 was significantly increased in ID patients
      relative to controls, and while IREG1 expression was 1.8-fold greater in treated
      HH patients, this was not statistically significant. HFE mRNA expression was not
      significantly different in any of the groups investigated relative to controls.
      CONCLUSIONS: These findings demonstrate that untreated HH patients do not have
      increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression
      of these molecules, reflecting the effect of phlebotomy induced erythropoiesis.
      Finally, HFE appears to play a minor role in the regulation of iron absorption by
      the duodenal enterocyte.

PMID- 15247189
TI  - Expression of somatostatin receptors in normal and cirrhotic human liver and in
      hepatocellular carcinoma.
AB  - BACKGROUND: Somatostatin analogues have been used with conflicting results to
      treat advanced hepatocellular carcinoma (HCC). The aim of this study was to
      investigate expression of somatostatin receptor (SSTR) subtypes in human liver,
      and to examine the effect of selective SSTR agonists on proliferation, apoptosis,
      and migration of hepatoma cells (HepG2, HuH7) and hepatic stellate cells (HSCs).
      METHODS: Expression of SSTRs in cell lines, normal and cirrhotic liver, and HCC
      was examined by immunohistochemistry and reverse transcription-polymerase chain
      reaction. Effects of SSTR agonists on proliferation and apoptosis of tumour cells
      and HSCs were assessed by the 5-bromo-2' deoxyuridine and TUNEL methods,
      respectively. The influence of SSTR agonists on migration was investigated using
      Boyden chambers. RESULTS: In normal liver, both hepatocytes and HSCs were
      negative for all five SSTRs. Cirrhotic liver and HCC as well as cultured hepatoma
      cells and HSCs expressed all five SSTRs, both at the protein and mRNA levels,
      except for HuH7 cells which did not immunoreact with SSTR3. None of the agonists
      influenced proliferation or apoptosis. However, compared with untreated cells, L
      797,591, an SSTR1 agonist, reduced migration of HepG2, HuH7, and HSCs
      significantly to 88 (7)% (p<0.05), 83 (11)% (p<0.05), and 67 (13)% (p<0.01),
      respectively. CONCLUSIONS: Cirrhotic liver and HCC express SSTRs. Although the
      somatostatin analogues used in this study did not affect proliferation and
      apoptosis, stimulation of SSTR1 may decrease invasiveness of HCC by reducing
      migration of hepatoma cells and/or HSCs. Clinical trials evaluating somatostatin
      analogues for the treatment of HCC should take these findings into account.

PMID- 15247191
TI  - Brain imaging and functional gastrointestinal disorders: has it helped our
      understanding?

PMID- 15247192
TI  - Endoscopic antireflux procedures.

PMID- 15247190
TI  - Iron, anaemia, and inflammatory bowel diseases.
AB  - Iron deficiency anaemia is one of the most common disorders in the world. Also,
      one third of inflammatory bowel disease (IBD) patients suffer from recurrent
      anaemia. Anaemia has significant impact on the quality of life of affected
      patients. Chronic fatigue, a frequent IBD symptom itself, is commonly caused by
      anaemia and may debilitate patients as much as abdominal pain or diarrhoea.
      Common therapeutic targets are the mechanisms behind anaemia of chronic disease
      and iron deficiency. It is our experience that virtually all patients with IBD
      associated anaemia can be successfully treated with a combination of iron sucrose
      and erythropoietin, which then may positively affect the misled immune response
      in IBD.

PMID- 15247194
TI  - Effect of cyclosporin A treatment on the in vivo regulation of type I MHC gene
      expression.
AB  - Rat soleus muscle consists predominantly of slow type I fibers. We have shown
      previously through deletion analysis that the highest level of reporter activity
      that we measure when injecting type I myosin heavy chain (MHC) promoter (MHC(1))
      linked luciferase plasmid into soleus muscles depends on the presence of a 550-bp
      upstream enhancer (3,450-2,900) region of the promoter. Because the calcineurin
      nuclear factor of activated T cells (NFAT) pathway has been implicated in the
      regulation of the slow muscle gene program, particularly the MHC(1) isoform, and
      the MHC(1) promoter contains several putative NFAT sites, we examined via
      deletion and mutation analyses whether this pathway is involved in the regulation
      of promoter activity in soleus. Nine days of treatment with the calcineurin
      inhibitor cyclosporin A (CsA) caused a significant decrease in activity of the 
      3,500- and -3,450-bp promoters compared with vehicle-treated rats. Truncation of
      the promoter to -2,900 bp or smaller reduced the activity and also eliminated the
      CsA responsiveness, thus implying that the enhancer region is required for CsA
      responsiveness. Surprisingly, mutating the two NFAT elements within the enhancer
      region had no obvious effect on promoter activity. CsA treatment resulted in an
      increase in the mRNA levels of fast-type IIa and IIx MHC isoforms, but RT-PCR
      analysis of MHC(1) pre-mRNA and mature mRNA expression in soleus muscles revealed
      no differences between vehicle- and CsA-treated rats. Although CsA affects the
      activity of the MHC(1) promoter, it appears that its effect is not through direct
      binding of NFAT to sites on the promoter.

PMID- 15247195
TI  - Influence of age and physical activity on the primary in vivo antibody and T cell
      mediated responses in men.
AB  - The aging immune system is characterized by the progressive decline in the
      antibody and T cell-mediated responses to antigen. Little is known, however,
      about the benefits of exercise in aging on the generation of a primary immune
      response to antigen and the subsequent antibody and memory T cell-mediated
      response. Most in vivo immune research to date has utilized vaccines or recall
      antigens to elicit an immune response. Therefore, the purpose of this experiment
      was to examine the association of aging and physical activity on the primary
      antibody and T cell response to the novel protein antigen keyhole-limpet
      hemocyanin (KLH). Forty-six physically active and sedentary, young (20-35 yr) and
      older (60-79 yr) men were recruited. Subjects were intramuscularly immunized with
      100 microg of KLH, and blood samples were collected at days 0, 7, 14, 21, and 28.
      Samples were measured for anti-KLH IgM, IgG, IgG1, and IgG2 by ELISA. On day 21
      after intramuscular KLH administration, subjects received an intradermal
      injection with 1 microg of KLH of inflammation recorded at 24, 48, 72, 96, and
      120 h to assess anti-KLH delayed-type hypersensitivity response. There was a
      significant reduction in all anti-KLH measures with aging except for anti-KLH
      IgG2. The physically active older group had significantly higher anti-KLH IgM,
      IgG, IgG1, and delayed-type hypersensitivity responses, but not IgG2 compared
      with the sedentary older group. In conclusion, regular physical activity in older
      men is associated with a more robust immune response to novel antigenic
      challenge.

PMID- 15247197
TI  - Blood flow switching among pulmonary capillaries is decreased during high
      hematocrit.
AB  - Pulmonary capillary perfusion within a single alveolar wall continually switches
      among segments, even when large-vessel hemodynamics are constant. The mechanism
      is unknown. We hypothesize that the continually varying size of plasma gaps
      between individual red blood cells affects the likelihood of capillary segment
      closure and the probability of cells changing directions at the next capillary
      junction. We assumed that an increase in hematocrit would decrease the average
      distance between red blood cells, thereby decreasing the switching at each
      capillary junction. To test this idea, we observed 26 individual alveolar
      capillary networks by using videomicroscopy of excised canine lung lobes that
      were perfused first at normal hematocrit (31-43%) and then at increased
      hematocrit (51-62%). The number of switches decreased by 38% during increased
      hematocrit (P < 0.01). These results support the idea that a substantial part of
      flow switching among pulmonary capillaries is caused by the particulate nature of
      blood passing through a complex network of tubes with continuously varying
      hematocrit.

PMID- 15247196
TI  - Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs.
AB  - Acute hypoxia increases pulmonary arterial pressure and vascular resistance.
      Previous studies in isolated smooth muscle and perfused lungs have shown that
      carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic
      pulmonary vasoconstriction (HPV). We studied whether CA inhibition by
      acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten
      chronically tracheotomized, conscious dogs were investigated in three protocols.
      In all protocols, the dogs breathed 21% O(2) for the first hour and then 8 or 10%
      O(2) for the next 4 h spontaneously via a ventilator circuit. The protocols were
      as follows: protocol 1: controls given no Acz, inspired O(2) fraction (Fi(O(2)))
      = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167
      microg.kg(-1).min(-1) continuously), Fi(O(2)) = 0.10; protocol 3: Acz given as
      above, but with Fi(O(2)) reduced to 0.08 to match the arterial Po(2) (Pa(O(2)))
      observed during hypoxia in controls. Pa(O(2)) was 37 Torr during hypoxia in
      controls, mean pulmonary arterial pressure increased from 17 +/- 1 to 23 +/- 1
      mmHg, and pulmonary vascular resistance increased from 464 +/- 26 to 679 +/- 40
      dyn.s(-1).cm(-5) (P < 0.05). In both Acz groups, mean pulmonary arterial pressure
      was 15 +/- 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440
      dyn.s(-1).cm(-5). These values did not change during hypoxia. In dogs given Acz
      at 10% O(2), the arterial Pa(O(2)) was 50 Torr owing to hyperventilation, whereas
      in those breathing 8% O(2) the Pa(O(2)) was 37 Torr, equivalent to controls. In
      conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The
      effect is not due to Acz-induced hyperventilation and higher alveolar Po(2), nor
      to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV
      suppression occurs despite the systemic acidosis with CA inhibition.

PMID- 15247198
TI  - Airway area distribution from the forced expiration maneuver.
AB  - The maximal expiratory flow-volume (MEFV) maneuver is a commonly used test of
      lung function. More detailed interpretation than is currently available might be
      useful to understand disease better. We propose that a previously published
      computational model (Lambert RK, Wilson TA, Hyatt RE, and Rodarte JR. J Appl
      Physiol 52: 44-56, 1982) can be used to deduce, from the MEFV curve, the serial
      distribution of airway areas in the larger airways. An automated procedure based
      on the simulated annealing technique was developed. It was tested with model
      generated flow data in which airway areas were reduced one generation at a time.
      The procedure accurately located the constriction and predicted its size within
      narrow bounds when the constriction was in the six most central generations of
      airways. More peripheral constrictions were detected but were not precisely
      located, nor were their sizes accurately evaluated. Airway areas of generations
      upstream of the constriction were usually overestimated. The procedure was
      applied to spirometric data obtained from eight volunteers (4 asthmatic and 4
      normal subjects) at baseline and after methacholine challenge. The predicted
      areas show individual differences both in absolute values, and in relative
      distribution of areas. This result shows that detailed information can be
      obtained from the MEFV curve through the use of a model. However, this initial
      model, which lacks airway smooth muscle, needs further refinement.

PMID- 15247199
TI  - Inhibitory effects of hyperthermia on mechanisms involved in autoresuscitation
      from hypoxic apnea in mice: a model for thermal stress causing SIDS.
AB  - The physiological mechanisms that might be involved in an association between
      heat stress and sudden infant death syndrome (SIDS) are obscure. We tested the
      hypothesis that a combination of acute hypoxia and elevated body temperature
      (T(B)) might prevent autoresuscitation from hypoxic apnea (AR). We exposed 21-day
      old mice (total = 216) to hyperthermia (40.5-43.5 degrees C), hypoxia, or a
      combination of the two. Neither hyperthermia alone (40.5-42.5 degrees C) nor
      hypoxia alone was found to be lethal, but the combination produced failure to AR
      during the first hypoxic exposure with increasing frequency as T(B) increased.
      The ability to withstand multiple hypoxic exposures was also reduced as T(B)
      increased. In contrast, heat stress causing moderate T(B) increase (40.5 degrees
      C) had no effect on survival. Increased T(B) (43.5 degrees C) reduced gasping
      duration and number of gasps. It increased heart rate during anoxia but did not
      alter gasping rate. Furthermore, the oxygen-independent increase in heart rate
      observed before gasping failure was usually delayed until after the last gasp in
      hyperthermic animals. Mild dehydration occurred during T(B) elevation, but this
      did not appear to be a primary factor in AR failure. We conclude that a thermal
      stress, which by itself is nonlethal, frequently prevents AR from hypoxic apnea.
      This may be due, at least in part, to decreased gasp number and duration as well
      as to hyperthermia-related asynchrony of reflexes regulating heart and gasping
      frequencies during attempted AR.

PMID- 15247200
TI  - Latency of pupillary reflex dilation during general anesthesia.
AB  - Areas of insensibility produced by neuraxial anesthesia or peripheral nerve
      blocks can be detected during general anesthesia by failure of noxious
      stimulation to trigger pupillary reflex dilation. We examined the latency of
      pupillary reflex dilation and the effect of fentanyl on the latency of reflex
      dilation during anesthesia in nine volunteers. We hypothesized that the reflex
      was generated by slowly conducting C nociceptive fibers and would be
      significantly delayed if a distal dermatome (L(4)) was stimulated compared with a
      proximal dermatome (C(5)). We also hypothesized that fentanyl would prolong the
      latency and alter the shape of the reflex. After induction of general anesthesia,
      pupillary reflex dilation was measured with an infrared pupillometer every 5 min
      after stimulations of the L(4) and C(5) dermatomes. Fentanyl (3 microg/kg) was
      then given intravenously. Pupillary reflex dilation latencies were calculated by
      examining each individual measurement. After 3 h, naloxone (400 microg) was given
      intravenously; anesthesia was then discontinued. Pupillary reflex dilation had a
      long latency and consisted of distinct early and late phases. No differences were
      found between latencies of reflex dilation after simulation of L(4) and C(5)
      dermatomes either before or after fentanyl administration. Fentanyl at high
      concentrations essentially eliminated pupillary reflex dilation; but over the 180
      min observation period, first early and then late dilation returned. Fentanyl
      produced a small increase in the latency of the initial early dilation. We
      conclude that pupillary reflex dilation during anesthesia is not initiated by
      slowly conducting C fibers and that fentanyl depresses the reflex in a
      stereotypical manner.

PMID- 15247201
TI  - Neural control of muscle blood flow during exercise.
AB  - Activation of skeletal muscle fibers by somatic nerves results in vasodilation
      and functional hyperemia. Sympathetic nerve activity is integral to
      vasoconstriction and the maintenance of arterial blood pressure. Thus the
      interaction between somatic and sympathetic neuroeffector pathways underlies
      blood flow control to skeletal muscle during exercise. Muscle blood flow
      increases in proportion to the intensity of activity despite concomitant
      increases in sympathetic neural discharge to the active muscles, indicating a
      reduced responsiveness to sympathetic activation. However, increased sympathetic
      nerve activity can restrict blood flow to active muscles to maintain arterial
      blood pressure. In this brief review, we highlight recent advances in our
      understanding of the neural control of the circulation in exercising muscle by
      focusing on two main topics: 1) the role of motor unit recruitment and muscle
      fiber activation in generating vasodilator signals and 2) the nature of
      interaction between sympathetic vasoconstriction and functional vasodilation that
      occurs throughout the resistance network. Understanding how these control systems
      interact to govern muscle blood flow during exercise leads to a clear set of
      specific aims for future research.

PMID- 15247202
TI  - Immediate exercise hyperemia: contributions of the muscle pump vs. rapid
      vasodilation.
AB  - A striking characteristic of the blood flow adaptation at exercise onset is the
      immediate and substantial increase in the first few (0-5 s) seconds of exercise.
      The purpose of this mini-review is to put into context the present evidence
      regarding mechanisms responsible for this phase of exercise hyperemia. One
      potential mechanism that has received much attention is the mechanical effect of
      muscle contraction (the muscle pump). The rapid vasodilatory mechanism(s) is
      another possible mechanism that has recently been shown to exist. This review
      will provide the reader with 1) an understanding of the basic physics of blood
      flow and the theories of muscle pump function, 2) a critical examination of
      evidence both for and against the contribution of the muscle pump or rapid
      vasodilatory mechanisms, and 3) an awareness of the limitations and impact of
      experimental models and exercise modes on the contribution of each of these
      mechanisms to the immediate exercise hyperemia. The inability to measure
      microvenular pressure continues to limit investigators to indirect assessments of
      the muscle pump vs. vasodilatory mechanism contributions to immediate exercise
      hyperemia in vivo. Future research directions should include examination of
      muscle-contraction-induced resistance vessel distortion as a trigger for rapid
      smooth muscle relaxation and further investigation into the exercise mode
      dependency of muscle pump vs. rapid vasodilatory contributions to immediate
      exercise hyperemia.

PMID- 15247204
TI  - Role of estrogen in nitric oxide- and prostaglandin-dependent modulation of
      vascular conductance during treadmill locomotion in rats.
AB  - Endothelial production of nitric oxide (NO) and prostaglandins (PG) may be
      greater in females than in males, increasing vasodilatory responses in females.
      Does sex influence the cardiovascular responses to dynamic exercise through
      estrogen-dependent modulation of NO and PG vasodilatory pathways? After the
      administration of hexamethonium, we assessed terminal aortic blood flow (TAQ),
      mean arterial pressure (MAP), and hindlimb vascular conductance (VC) in four
      groups of rats (6 males, 5 females, 5 ovariectomized females, and 6
      ovariectomized females with chronic estrogen supplementation) during graded mild
      intensity treadmill locomotion (5-15 m/min, 0 degrees grade, 2 min). All rats
      repeated exercise after cyclooxygenase inhibition (indomethacin) and then again
      after NO synthase inhibition (nitro-l-arginine methyl ester) to examine the roles
      of NO and PG. Regression analysis was used to determine the influence of sex and
      plasma 17beta-estradiol on TAQ, MAP, and VC. The analysis revealed that female
      sex did not influence TAQ but reduced MAP and increased VC at rest and during
      exercise conditions. Plasma 17beta-estradiol (measured by immunoassay)
      significantly decreased MAP and increased TAQ and VC, irrespective of sex.
      Cyclooxygenase inhibition eliminated the significant association between MAP and
      estrogen, suggesting that estrogenic modulation occurred through PG-dependent
      processes. In contrast, the significant influence of estrogen on TAQ and VC was
      eliminated after NO synthase inhibition. On the basis of the overall findings of
      this study, estrogen influenced the vascular responses to dynamic exercise
      through PG- and NO-dependent pathways, but this occurred independent of sex.

PMID- 15247205
TI  - Prediction of fluid responsiveness: searching for the Holy Grail.

PMID- 15247206
TI  - A spurious correlation.

PMID- 15247207
TI  - A computed method for noninvasive MRI assessment of pulmonary arterial
      hypertension.

PMID- 15247208
TI  - Ubiquitin is conjugated by membrane ubiquitin ligase to three sites, including
      the N terminus, in transmembrane region of mammalian 3-hydroxy-3-methylglutaryl
      coenzyme A reductase: implications for sterol-regulated enzyme degradation.
AB  - The stability of the endoplasmic reticulum (ER) glycoprotein 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGR), the key enzyme in cholesterol
      biosynthesis, is negatively regulated by sterols. HMGR is anchored in the ER via
      its N-terminal region, which spans the membrane eight times and contains a sterol
      sensing domain. We have previously established that degradation of mammalian HMGR
      is mediated by the ubiquitin-proteasome system (Ravid, T., Doolman, R., Avner,
      R., Harats, D., and Roitelman, J. (2000) J. Biol. Chem. 275, 35840-35847). Here
      we expressed in HEK-293 cells an HA-tagged-truncated version of HMGR that
      encompasses all eight transmembrane spans (350 N-terminal residues). Similar to
      endogenous HMGR, degradation of this HMG(350)-3HA protein was accelerated by
      sterols, validating it as a model to study HMGR turnover. The degradation of
      HMG(240)-3HA, which lacks the last two transmembrane spans yet retains an intact
      sterol-sensing domain, was no longer accelerated by sterols. Using HMG(350)-3HA,
      we demonstrate that transmembrane region of HMGR is ubiquitinated in a sterol
      regulated fashion. Through site-directed Lys --> Arg mutagenesis, we pinpoint
      Lys(248) and Lys(89) as the internal lysines for ubiquitin attachment, with
      Lys(248) serving as the major acceptor site for polyubiquitination. Moreover, the
      data indicate that the N terminus is also ubiquitinated. The degradation rates of
      the Lys --> Arg mutants correlates with their level of ubiquitination. Notably,
      lysine-less HMG(350)-3HA is degraded faster than wild-type protein, suggesting
      that lysines other than Lys(89) and Lys(248) attenuate ubiquitination at the
      latter residues. The ATP-dependent ubiquitination of HMGR in isolated microsomes
      requires E1 as the sole cytosolic protein, indicating that ER-bound E2 and E3
      enzymes catalyze this modification. Polyubiquitination of HMGR is correlated with
      its extraction from the ER membrane, a process likely to be assisted by cytosolic
      p97/VCP/Cdc48p-Ufd1-Npl4 complex, as only ubiquitinated HMGR pulls down p97.

PMID- 15247209
TI  - Oxanine DNA glycosylase activity from Mammalian alkyladenine glycosylase.
AB  - Oxanine (Oxa) is a deaminated base lesion derived from guanine in which the N(1)
      nitrogen is substituted by oxygen. This work reports the mutagenicity of oxanine
      as well as oxanine DNA glycosylase (ODG) activities in mammalian systems. Using
      human DNA polymerase beta, deoxyoxanosine triphosphate is only incorporated
      opposite cytosine (Cyt). When an oxanine base is in a DNA template, Cyt is
      efficiently incorporated opposite the template oxanine; however, adenine and
      thymine are also incorporated opposite Oxa with an efficiency approximately 80%
      of a Cyt/Oxa (C/O) base pair. Guanine is incorporated opposite Oxa with the least
      efficiency, 16% compared with cytosine. ODG activity was detected in several
      mammalian cell extracts. Among the known human DNA glycosylases tested, human
      alkyladenine glycosylase (AAG) shows ODG activity, whereas hOGG1, hNEIL1, or
      hNEIL2 did not. ODG activity was detected in spleen cell extracts of wild type
      age-matched mice, but little activity was observed in that of Aag knock-out mice,
      confirming that the ODG activity is intrinsic to AAG. Human AAG can excise Oxa
      from all four Oxa-containing double-stranded base pairs, Cyt/Oxa, Thy/Oxa,
      Ade/Oxa, and Gua/Oxa, with no preference to base pairing. Surprisingly, AAG can
      remove Oxa from single-stranded Oxa-containing DNA as well. Indeed, AAG can also
      remove 1,N(6)-ethenoadenine from single-stranded DNA. This study extends the
      deaminated base glycosylase activities of AAG to oxanine; thus, AAG is a
      mammalian enzyme that can act on all three purine deamination bases,
      hypoxanthine, xanthine, and oxanine.

PMID- 15247210
TI  - Reversible assembly of the ATP-binding cassette transporter Mdl1 with the F1F0
      ATP synthase in mitochondria.
AB  - The half-ABC transporter Mdl1 is localized in the inner membrane of mitochondria
      and mediates the export of peptides generated upon proteolysis of mitochondrial
      proteins. The physiological role of the peptides released from mitochondria is
      currently not understood. Here, we have analyzed the oligomeric state of Mdl1 in
      the inner membrane and demonstrate nucleotide-dependent binding to the F(1)F(0)
      ATP synthase. Mdl1 forms homo-oligomeric, presumably dimeric complexes in the
      presence of ATP, but was found in association with the F(1)F(0)-ATP synthase at
      low ATP levels. Mdl1 binds membrane-embedded parts of the ATP synthase complex
      after the assembly of the F(1) and F(0) moieties. Although independent of Mdl1
      activity, complex formation is impaired upon inhibition of the F(1)F(0)-ATP
      synthase with oligomycin or N,N'-dicyclohexylcarbodiimide. These results are
      consistent with an activation of Mdl1 upon dissociation from the ATP synthase and
      suggest a link of peptide export from mitochondria to the activity of the
      F(1)F(0)-ATP synthase and the cellular energy metabolism.

PMID- 15247211
TI  - Overexpression of the catalytic subunit of protein phosphatase 2A impairs cardiac
      function.
AB  - Reversible protein phosphorylation is an essential regulatory mechanism in many
      cellular functions. In contrast to protein kinases, the role and regulation of
      protein phosphatases has remained ambiguous. To address this issue, we generated
      transgenic mice that overexpress the catalytic subunit alpha of protein
      phosphatase 2A (PP2A) (PP2Acalpha) in the heart driven by the alpha-myosin heavy
      chain promoter. Overexpression of the PP2Acalpha gene in the heart led to
      increased levels of the transgene both at RNA and protein levels. This was
      accompanied by a significant increase of PP2A enzyme activity in the myocardium.
      Morphological analysis revealed isles of necrosis and fibrosis. The
      phosphorylation state of phospholamban, troponin inhibitor, and eukaryotic
      elongation factor 2 was reduced significantly. The expression of junctional
      (calsequestrin) and free SR proteins (SERCA and phospholamban) was not altered.
      Whereas no increase in morbidity or mortality was noted, transgenic mice
      developed cardiac hypertrophy and reduced contractility of the heart, as well as
      cardiac dilatation as shown by biplane echocardiography. Taken together, these
      findings are indicative of the fundamental role of PP2A in cardiac function and
      imply that disturbances in protein phosphatases expression and activity may cause
      or aggravate the course of cardiac diseases.

PMID- 15247212
TI  - Entry of newly synthesized GLUT4 into the insulin-responsive storage compartment
      is dependent upon both the amino terminus and the large cytoplasmic loop.
AB  - We have recently reported that following initial biosynthesis, the GLUT4 protein
      exits the Golgi apparatus and directly enters the insulin-responsive
      compartment(s) without transiting the plasma membrane. To investigate the
      structural motifs involved in these initial sorting events, we have generated a
      variety of loss-of-function and gain-of-function GLUT4/GLUT1 chimera proteins.
      Substitution of the GLUT4 carboxyl-terminal domain with GLUT1 had no significant
      effect on the acquisition of insulin responsiveness. In contrast, substitution of
      either the GLUT4 amino-terminal domain or the large cytoplasmic loop between
      transmembrane domains 6 and 7 resulted in the rapid default of GLUT4 to the
      plasma membrane with blunted insulin response. Consistent with these findings,
      substitution of the amino-terminal, cytoplasmic loop, or carboxyl-terminal
      domains individually into GLUT1 backbone did not recapitulate normal GLUT4
      trafficking. Similarly, dual substitutions of the GLUT1 amino and carboxyl
      termini with GLUT4 domains or the combination of the cytoplasmic loop plus the
      carboxyl terminus failed to display normal GLUT4 trafficking. However, the dual
      replacement of the amino terminus plus the cytoplasmic loop of GLUT4 in the GLUT1
      backbone resulted in a complete restoration of normal GLUT4 trafficking. Alanine
      scanning mutagenesis of the GLUT4 amino terminus demonstrated that Phe(5) and
      Ile(8) within the FQQI motif and, to a lesser extent, Asp(12)/Gly(13) were
      necessary for the appropriate initial trafficking following biosynthesis. In
      addition, amino acids 229-271 in the large intracellular loop between
      transmembrane domains 6 and 7 functionally cooperated with the amino-terminal
      domain. These data demonstrate that initial trafficking of GLUT4 from the Golgi
      to the insulin-responsive GLUT4 compartment requires the functional interaction
      of two distinct domains.

PMID- 15247213
TI  - The tyrosine kinase inhibitor STI571 induces cellular clearance of PrPSc in prion
      infected cells.
AB  - The conversion of the cellular prion protein (PrP(c)) into pathologic PrP(Sc) and
      the accumulation of aggregated PrP(Sc) are hallmarks of prion diseases. A variety
      of experimental approaches to interfere with prion conversion have been reported.
      Our interest was whether interference with intracellular signaling events has an
      impact on this conversion process. We screened approximately 50 prototype
      inhibitors of specific signaling pathways in prion-infected cells for their
      capacity to affect prion conversion. The tyrosine kinase inhibitor STI571 was
      highly effective against PrP(Sc) propagation, with an IC(50) of < or =1 microM.
      STI571 cleared prion-infected cells in a time- and dose-dependent manner from
      PrP(Sc) without influencing biogenesis, localization, or biochemical features of
      PrP(c). Interestingly, this compound did not interfere with the de novo formation
      of PrP(Sc) but activated the lysosomal degradation of pre-existing PrP(Sc),
      lowering the half-life of PrP(Sc) from > or =24 h to <9 h. Our data indicate that
      among the kinases known to be inhibited by STI571, c-Abl is likely responsible
      for the observed anti-prion effect. Taken together, we demonstrate that treatment
      with STI571 strongly activates the lysosomal degradation of PrP(Sc) and that
      substances specifically interfering with cellular signaling pathways might
      represent a novel class of anti-prion compounds.

PMID- 15247214
TI  - In vitro identification and characterization of an early complex linking HIV-1
      genomic RNA recognition and Pr55Gag multimerization.
AB  - The minimal protein requirements that drive virus-like particle formation of
      human immunodeficiency virus type 1 (HIV-1) have been established. The C-terminal
      domain of capsid (CTD-CA) and nucleocapsid (NC) are the most important domains in
      a so-called minimal Gag protein (mGag). The CTD is essential for Gag
      oligomerization. NC is known to bind and encapsidate HIV-1 genomic RNA. The
      spacer peptide, SP1, located between CA and NC is important for the
      multimerization process, viral maturation and recognition of HIV-1 genomic RNA by
      NC. In this study, we show that NC in the context of an mGag protein binds HIV-1
      genomic RNA with almost 10-fold higher affinity. The protein region encompassing
      the 11th alpha-helix of CA and the proposed alpha-helix in the CA/SP1 boundary
      region play important roles in this increased binding capacity. Furthermore,
      sequences downstream from stem loop 4 of the HIV-1 genomic RNA are also important
      for this RNA-protein interaction. In gel shift assays using purified mGag and a
      model RNA spanning the region from +223 to +506 of HIV-1 genomic RNA, we have
      identified an early complex (EC) formation between 2 proteins and 1 RNA molecule.
      This EC was not present in experiments performed with a mutant mGag protein,
      which contains a CTD dimerization mutation (M318A). These data suggest that the
      dimerization interface of the CTD plays an important role in EC formation, and,
      as a consequence, in RNA-protein association and multimerization. We propose a
      model for the RNA-protein interaction, based on previous results and those
      presented in this study.

PMID- 15247215
TI  - Processing mutations located throughout the human multidrug resistance P
      glycoprotein disrupt interactions between the nucleotide binding domains.
AB  - The most common cause of cystic fibrosis is misfolding of the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein because of deletion of residue
      Phe-508 (DeltaF508). P-glycoprotein (P-gp) is an ideal model protein for studying
      how mutations disrupt folding of ATP-binding cassette proteins such as CFTR
      because specific chemical chaperones can be used to correct folding defects.
      Interactions between the nucleotide binding domains (NBDs) are critical because
      ATP binds at the interface between the NBDs. Here, we used disulfide cross
      linking between cysteines in the Walker A sites and the LSGGQ signature sequences
      to test whether processing mutations located throughout P-gp disrupted
      interactions between the NBDs. We found that mutations present in the cytoplasmic
      loops, transmembrane segments, and linker regions or deletion of Tyr-490
      (equivalent to Phe-508 in CFTR) inhibited cross-linking between the NBDs.
      Deletion of Phe-508 in the P-gp/CFTR chimera also inhibited cross-linking between
      the NBDs. Cross-linking was restored, however, when the mutants were expressed in
      the presence of the chemical chaperone cyclosporin A. The "rescued" mutants
      exhibited drug-stimulated ATPase activity, and cross-linking between the NBDs was
      inhibited by vanadate trapping of nucleotide. These results together with our
      previous findings (Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2002) J. Biol.
      Chem. 277, 27585-27588) indicate that processing mutations disrupt interactions
      among all four domains. It appears that cross-talk between the cytoplasmic and
      the transmembrane domains is required for establishment of proper domain-domain
      interactions that occur during folding of ATP-binding cassette protein
      transporters.

PMID- 15247216
TI  - An exonic splicing enhancer offsets the atypical GU-rich 3' splice site of human
      apolipoprotein A-II exon 3.
AB  - Human apolipoprotein A-II (apoA-II) intron 2/exon 3 junction shows a peculiar
      tract of alternating pyrimidines and purines (GU tract) that makes the acceptor
      site deviate significantly from the consensus. However, apoA-II exon 3 is
      constitutively included in mRNA. We have studied this unusual exon definition by
      creating a construct with the genomic fragment encompassing the whole gene from
      apoA-II and its regulatory regions. Transient transfections in Hep3B cells have
      shown that deletion or replacement of the GU repeats at the 3' splice site
      resulted in a decrease of apoA-II exon 3 inclusion, indicating a possible role of
      the GU tract in splicing. However, a 3' splice site composed of the GU tract in
      heterologous context, such as the extra domain A of human fibronectin or cystic
      fibrosis transmembrane conductance regulator exon 9, resulted in total skipping
      of the exons. Next, we identified the exonic cis-acting elements that may affect
      the splicing efficiency of apoA-II exon 3 and found that the region spanning from
      nucleotide 87 to 113 of human apoA-II exon 3 is essential for its inclusion in
      the mRNA. Overlapping deletions and point mutations (between nucleotides 91 and
      102) precisely defined an exonic splicing enhancer (ESEwt). UV cross-linking
      assays followed by immunoprecipitation with anti-SR protein monoclonal antibodies
      showed that ESEwt, but not mutated ESE RNA, was able to bind both alternative
      splicing factor/splicing factor 2 and SC35. Furthermore, overexpression of both
      splicing factors enhanced exon 3 inclusion. These results show that this protein
      ESE interaction is able to promote the incorporation of exon 3 in mRNA and
      suggest that they can rescue the splicing despite the noncanonical 3' splice
      site.

PMID- 15247217
TI  - The 5'-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate
      and lipid metabolism in glycolytic skeletal muscle.
AB  - 5'-AMP-activated protein kinase (AMPK) is a metabolic stress sensor present in
      all eukaryotes. A dominant missense mutation (R225Q) in pig PRKAG3, encoding the
      muscle-specific gamma3 isoform, causes a marked increase in glycogen content. To
      determine the functional role of the AMPK gamma3 isoform, we generated transgenic
      mice with skeletal muscle-specific expression of wild type or mutant (225Q) mouse
      gamma3 as well as Prkag3 knockout mice. Glycogen resynthesis after exercise was
      impaired in AMPK gamma3 knock-out mice and markedly enhanced in transgenic mutant
      mice. An AMPK activator failed to increase skeletal muscle glucose uptake in AMPK
      gamma3 knock-out mice, whereas contraction effects were preserved. When placed on
      a high fat diet, transgenic mutant mice but not knock-out mice were protected
      against excessive triglyceride accumulation and insulin resistance in skeletal
      muscle. Transfection experiments reveal the R225Q mutation is associated with
      higher basal AMPK activity and diminished AMP dependence. Our results validate
      the muscle-specific AMPK gamma3 isoform as a therapeutic target for prevention
      and treatment of insulin resistance.

PMID- 15247218
TI  - A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative
      stress induced by glucose deprivation in Schizosaccharomyces pombe.
AB  - In Schizosaccharomyces pombe, glucose concentrations below a certain threshold
      trigger the stress-activated protein kinase (SAPK) signal transduction pathway
      and promote increased transcription of Atf1-dependent genes coding for the
      general stress response. Removal of glucose specifically induces the nuclear
      accumulation of green fluorescent protein-labeled Pap1 (GFP-Pap1) and the
      expression of genes dependent on this transcription factor. In contrast,
      depletion of the nitrogen source triggers the SAPK pathway but does not activate
      Pap1-dependent gene transcription, indicating that carbon stress rather than
      growth arrest leads to an endogenous oxidative condition that favors nuclear
      accumulation of Pap1. The reductant agents glutathione or N-acetylcysteine
      suppress the nuclear accumulation of GFP-Pap1 induced by glucose deprivation
      without inhibiting the activation of the MAPK Sty1. In addition, cells expressing
      a mutant GFP-Pap1 unable to accumulate into the nucleus upon hydrogen peroxide
      mediated oxidative stress failed to show this protein into the nucleus in the
      absence of glucose. These results support the concept of a concerted action
      between the SAPK pathway and the Pap1 transcription factor during glucose
      exhaustion by which glucose limitation induces activation of the SAPK pathway
      prior to the oxidative stress caused by glucose deprivation. The ensuing
      induction of Atf1-dependent genes (catalase) decreases the level of
      hydroperoxides allowing Pap1 nuclear accumulation and function. Congruent with
      this interpretation, glucose-depleted cells show higher adaptive response to
      exogenous oxidative stress than those maintained in the presence of glucose.

PMID- 15247219
TI  - Regulation of vascular endothelial growth factor receptor 2-mediated
      phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase
      activities.
AB  - Exposure of endothelial cells to vascular endothelial growth factor (VEGF)
      induced tyrosine phosphorylation of focal adhesion kinase (FAK) on site Tyr(407),
      an effect that required the association of VEGF receptor 2 (VEGFR2) with HSP90.
      The association of VEGFR2 with HSP90 involved the last 130 amino acids of VEGFR2
      and was blocked by geldanamycin, a specific inhibitor of HSP90. Moreover,
      geldanamycin inhibited the VEGF-induced activation of the small GTPase RhoA,
      which resulted in an inhibition of phosphorylation of FAK on site Tyr(407). In
      this context, the inhibition of RhoA kinase (ROCK) with Y27632 or by expression
      of dominant negative forms of RhoA or ROCK impaired the VEGF-induced
      phosphorylation of Tyr(407) within FAK. In contrast to phosphorylation of
      Tyr(861), the phosphorylation of site Tyr(407) was insensitive to Src kinase
      inhibition by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine
      (PP2). We also found that the recruitment of paxillin to FAK was inhibited by
      geldanamycin but not by PP2, whereas both geldanamycin and PP2 inhibited the
      recruitment of vinculin to FAK. In accordance, the recruitment of paxillin and
      vinculin to FAK was inhibited in cells that express the mutant FAK-Y407F, whereas
      the expression of the mutant Y861F inhibited the recruitment of paxillin but not
      of vinculin. Importantly, cell migration was abolished in cells in which the
      signal from the VEGFR2-HSP90 pathway was blocked by the expression of
      Delta130VEGFR2, a deletant of VEGFR2 that does not associate with HSP90. Our
      findings underscore for the first time the key role played by the VEGFR2-HSP90
      RhoA-ROCK-FAK/Tyr(407) pathway in transducing the VEGF signal that leads to the
      assembly of focal adhesions and endothelial cell migration.

PMID- 15247220
TI  - Identification of distinct N-terminal truncated forms of prion protein in
      different Creutzfeldt-Jakob disease subtypes.
AB  - In prion diseases, the cellular prion protein (PrP(C)) is converted to an
      insoluble and protease-resistant abnormal isoform termed PrP(Sc). In different
      prion strains, PrP(Sc) shows distinct sites of endogenous or exogenous
      proteolysis generating a core fragment named PrP27-30. Sporadic Creutzfeldt-Jakob
      disease (sCJD), the most frequent human prion disease, clinically presents with a
      variety of neurological signs. As yet, the clinical variability observed in sCJD
      has not been fully explained by molecular studies relating two major types of
      PrP27-30 with unglycosylated peptides of 21 (type 1) and 19 kDa (type 2) and the
      amino acid methionine or valine at position 129. Recently, smaller C-terminal
      fragments migrating at 12 and 13 kDa have been detected in different sCJD
      phenotypes, but their significance remains unclear. By using two-dimensional
      immunoblot with anti-PrP antibodies, we identified two novel groups of protease
      resistant PrP fragments in sCJD brain tissues. All sCJD cases with type 1 PrP27
      30, in addition to MM subjects with type 2 PrP27-30, were characterized by the
      presence of unglycosylated PrP fragments of 16-17 kDa. Conversely, brain
      homogenates from patients VV and MV with type 2 PrP27-30 contained fully
      glycosylated PrP fragments, which after deglycosylation migrated at 17.5-18 kDa.
      Interestingly, PrP species of 17.5-18 kDa matched deglycosylated forms of the C1
      PrP(C) fragment and were associated with tissue PrP deposition as plaque-like
      aggregates or amyloid plaques. These data show the presence of multiple PrP(Sc)
      conformations in sCJD and, in addition, shed new light on the correlation between
      sCJD phenotypes and disease-associated PrP molecules.

PMID- 15247221
TI  - The H,K-ATPase beta subunit as a model to study the role of N-glycosylation in
      membrane trafficking and apical sorting.
AB  - The role of N-glycosylation in trafficking of an apical membrane protein, the
      gastric H,K-ATPase beta subunit linked to yellow fluorescent protein, was
      analyzed in polarized LLC-PK1 cells by confocal microscopy and surface-specific
      biotinylation. Deletion of the N-glycosylation sites at N1, N3, N5, and N7 but
      not at N2, N4, and N6 significantly slowed endoplasmic reticulum-to-Golgi
      trafficking, impaired apical sorting, and enhanced endocytosis from the apical
      membrane, resulting in decreased apical expression. Golgi mannosidase inhibition
      to prevent carbohydrate chain branching and elongation resulted in faster
      internalization and degradation of the beta subunit, indicating that terminal
      glycosylation is important for stabilization of the protein in the apical
      membrane and protection of internalized protein from targeting to the degradation
      pathway. The decrease in the apical content of the beta subunit was less with
      mannosidase inhibition compared with that found in the N1, N3, N5, and N7 site
      mutants, suggesting that the core region sugars are more important than the
      terminal sugars for apical sorting.

PMID- 15247222
TI  - Calmodulin-mediated activation of Akt regulates survival of c-Myc-overexpressing
      mouse mammary carcinoma cells.
AB  - c-Myc-overexpressing mammary epithelial cells are proapoptotic; their survival is
      strongly promoted by epidermal growth factor (EGF). We now demonstrate that EGF
      induced Akt activation and survival in transgenic mouse mammary tumor virus-c-Myc
      mouse mammary carcinoma cells are both calcium/calmodulin-dependent. Akt
      activation is abolished by the phospholipase C-gamma inhibitor U-73122, by the
      intracellular calcium chelator BAPTA-AM, and by the specific calmodulin
      antagonist W-7. These results implicate calcium/calmodulin in the activation of
      Akt in these cells. In addition, Akt activation by serum and insulin is also
      inhibited by W-7. EGF-induced and calcium/calmodulin-mediated Akt activation
      occurs in both tumorigenic and non-tumorigenic mouse and human mammary epithelial
      cells, independent of their overexpression of c-Myc. These results imply that
      calcium/calmodulin may be a common regulator of Akt activation, irrespective of
      upstream receptor activator, mammalian species, and transformation status in
      mammary epithelial cells. However, only c-Myc-overexpressing mouse mammary
      carcinoma cells (but not normal mouse mammary epithelial cells) undergo apoptosis
      in the presence of the calmodulin antagonist W-7, indicating the vital selective
      role of calmodulin for survival of these cells. Calcium/calmodulin-regulated Akt
      activation is mediated directly by neither calmodulin kinases nor
      phosphatidylinositol 3-kinase (PI-3 kinase). Pharmacological inhibitors of
      calmodulin kinase kinase and calmodulin kinases II and III do not inhibit EGF
      induced Akt activation, and calmodulin antagonist W-7 does not inhibit
      phosphotyrosine-associated PI-3 kinase activation. Akt is, however, co
      immunoprecipitated with calmodulin in an EGF-dependent manner, which is inhibited
      by calmodulin antagonist W-7. We conclude that calmodulin may serve a vital
      regulatory function to direct the localization of Akt to the plasma membrane for
      its activation by PI-3 kinase.

PMID- 15247223
TI  - Characterization of a novel acid phosphatase from embryonic axes of kidney bean
      exhibiting vanadate-dependent chloroperoxidase activity.
AB  - A novel colorless acid phosphatase (KeACP), which was distinct from the kidney
      bean purple acid phosphatase, was purified to apparent homogeneity and cloned
      from embryonic axes of kidney bean (Phaseolus vulgaris L. Ohfuku) during
      germination. When orthovanadate (VO(4)(-3)) is added to the apo form of the
      enzyme, KeACP uniquely exhibits the chloroperoxidase activity with loss of
      phosphatase activity. This is the first demonstration that KeACP is a vanadate
      dependent chloroperoxidase in plants to be characterized and suggests that KeACP
      may play a role in modifying a wide variety of chlorinated compounds that are
      present in higher plants. The enzyme is a dimer that presents three forms made up
      of the combination of the dominant 56-kDa and the minor 45-kDa subunits, and both
      subunits contain carbohydrate. The full-length cDNA of the KeACP gene is 1641
      nucleotides, and this sequence is predicted to encode a protein having 457 amino
      acid residues (52,865 Da), including a signal peptide. The complete nucleotide
      sequence of the genomic DNA (3228 bp) of KeACP consists of seven exons and six
      introns. Northern blot analysis demonstrated that the KeACP gene was expressed
      specifically in embryonic axes of the kidney bean, and its expression coincided
      with elongation of the embryonic axis during germination.

PMID- 15247224
TI  - Anchoring of surface proteins to the cell wall of Staphylococcus aureus. A
      conserved arginine residue is required for efficient catalysis of sortase A.
AB  - Surface proteins of Staphylococcus aureus are anchored to the cell wall envelope
      by a mechanism requiring a C-terminal sorting signal with an LPXTG motif. Sortase
      A cleaves surface proteins between the threonine (T) and the glycine (G) residues
      of the LPXTG motif and catalyzes the formation of an amide bond between the
      carboxyl group of threonine at the C-terminal end of polypeptides and the amino
      group of pentaglycine cross-bridges of cell wall peptidoglycan. Previous work
      showed that Cys(184) and His(120) of sortase A are absolutely essential for
      catalysis; however an active site thiolateimidazolium ion pair may not be formed.
      The three-dimensional crystal structure of sortase A revealed that Arg(197) is
      located in close proximity to both the active site Cys(184) and the scissile
      peptide bond between threonine and glycine. We show here that substitution of
      Arg(197) with alanine, lysine, or histidine severely reduced sortase A function
      both in vivo and in vitro, whereas Asn(98), which had earlier been implicated in
      hydrogen bonding to His(120), was found to be dispensable for catalysis. As the
      structural proximity of Arg(197) and Cys(184) is conserved in sortase enzymes and
      as ionization of the Cys(184) sulfhydryl group seems required for sortase
      activity, we propose that Arg(197) may function as a base, facilitating thiolate
      formation during sortase-mediated cleavage and transpeptidation reactions.

PMID- 15247225
TI  - Bacillus subtilis DesR functions as a phosphorylation-activated switch to control
      membrane lipid fluidity.
AB  - The Des pathway of Bacillus subtilis regulates the synthesis of the cold-shock
      induced membrane-bound enzyme Delta5-fatty acid desaturase (Delta5-Des). A
      central component of the Des pathway is the response regulator, DesR, which is
      activated by a membrane-associated kinase, DesK, in response to a decrease in
      membrane lipid fluidity. Despite genetic and biochemical studies, specific
      details of the interaction between DesR and the DNA remain unknown. In this study
      we show that only the phosphorylated form of protein DesR is able to bind to a
      regulatory region immediately upstream of the promoter of the Delta5-Des gene
      (Pdes). Phosphorylation of the regulatory domain of dimeric DesR promotes, in a
      cooperative fashion, the hierarchical occupation of two adjacent, non-identical,
      DesR-P DNA binding sites, so that there is a shift in the equilibrium toward the
      tetrameric active form of the response regulator. Subsequently, this
      phosphorylation signal propagation leads to the activation of the des gene
      through recruitment of RNA polymerase to Pdes. This is the first dissected
      example of a transcription factor functioning as a phosphorylation-activated
      switch for a cold-shock gene, allowing the cell to optimize the fluidity of
      membrane phospholipids.

PMID- 15247226
TI  - Tryptophan scanning mutagenesis of the gammaM4 transmembrane domain of the
      acetylcholine receptor from Torpedo californica.
AB  - The periodicity of structural and functional effects induced by tryptophan
      scanning mutagenesis has been successfully used to define function and secondary
      structure of various transmembrane domains of the acetylcholine receptor of
      Torpedo californica. We expand the tryptophan scanning of the AchR of T.
      californica to the gammaM4 transmembrane domain (gammaTM4) by introducing
      tryptophan, at residues 451-462, along the gammaTM4. Wild type (WT) and mutant
      AChR were expressed in Xenopus laevis oocytes. Using [(125)I]alpha-bungarotoxin
      binding assays and voltage clamp, we determined that the nAChR expression,
      EC(50), and Hill coefficient values for WT are 1.8 +/- 0.4 fmol, 30.3 +/- 1.1
      microM, and 1.8 +/- 0.3, respectively. Mutations L456W, F459W, and G462W induce a
      significant increase in nAChR expression (2.8 +/- 0.5, 3.6 +/- 0.6, and 3.0 +/-
      0.5 fmol, respectively) when compared with WT. These data suggest that these
      residues are important for AChR oligomerization. Mutations A455W, L456W, F459W,
      and G462W result in a significant decrease in EC(50) (19.5 +/- 1.7, 11.4 +/- 0.7,
      16.4 +/- 3.8, and 19.1 +/- 2.6 microM, respectively), thus suggesting a gain in
      function when compared with WT. In contrast, mutation L458W induced an increase
      in EC(50) (42.8 +/- 6.8 microM) or loss in function when compared with WT. The
      Hill coefficient values were the same for WT and all of the mutations studied.
      The periodicity in function (EC(50) and macroscopic peak current) and nAChR
      expression reveals an average of 3.3 and 3.0 amino acids respectively, thus
      suggesting a helical secondary structure for the gammaTM4.

PMID- 15247227
TI  - High affinity streptococcal binding to human fibronectin requires specific
      recognition of sequential F1 modules.
AB  - Fibronectin (Fn) binding by the Streptococcus pyogenes protein SfbI has been
      shown to trigger integrin-dependent internalization of this pathogen by human
      epithelial and endothelial cells. Here, using nuclear magnetic resonance
      spectroscopy and isothermal titration calorimetry in a dissection approach, the
      basis for the specificity and high affinity of the interaction between the N
      terminal domain of Fn and SfbI is revealed. Each of the five Fn type 1 modules is
      directly involved in the interaction and is recognized by short consecutive
      motifs within the repeat region of SfbI. Crucially, these motifs must be combined
      in the correct order to form a high affinity ligand for the N-terminal domain of
      Fn.

PMID- 15247228
TI  - Complexity of translationally controlled transcription factor Sp3 isoform
      expression.
AB  - Sp3 is a ubiquitous transcription factor closely related to Sp1. Both proteins
      contain a highly conserved DNA-binding domain close to the C terminus and two
      glutamine-rich domains in the N-terminal moiety. Immunoblot analyses of Sp3
      reveal a striking complex protein pattern of up to eight distinct species. This
      pattern is not observed in Sp3-deficient cell lines showing that all signals
      reflect Sp3 antigen. In this study, we have unraveled the complexity of Sp3
      expression. We show that four isoforms of Sp3 that retain different parts of the
      N terminus are expressed in vivo. The four isoforms derive from alternative
      translational start sites at positions 1, 37, 856, and 907. An upstream open
      reading frame located at position -47 to -18 regulates expression of the two long
      isoforms. Unlike Sp1, none of the Sp3 isoforms is glycosylated. However, all four
      isoforms become SUMO-modified in vivo and in vitro specifically and exclusively
      at lysine residue 551. The transcriptional activity of the two long isoforms
      strongly depends on the promoter settings, whereas the small isoforms appear to
      be inactive. The transcriptional activity of all the Sp3 isoforms is regulated by
      SUMO modification. Our results demonstrate that Sp3 has many unique features and
      is not simply a functional equivalent of Sp1.

PMID- 15247229
TI  - A PTEN-like phosphatase with a novel substrate specificity.
AB  - We show that a novel PTEN-like phosphatase (PLIP) exhibits a unique preference
      for phosphatidylinositol 5-phosphate (PI(5)P) as a substrate in vitro. PI(5)P is
      the least characterized member of the phosphoinositide (PI) family of lipid
      signaling molecules. Recent studies suggest a role for PI(5)P in a variety of
      cellular events, such as tumor suppression, and in response to bacterial
      invasion. Determining the means by which PI(5)P levels are regulated is therefore
      key to understanding these cellular processes. PLIP is highly enriched in testis
      tissue and, similar to other PI phosphatases, exhibits poor activity against
      several proteinaceous substrates. Despite a recent report suggesting a role for
      PI(5)P in the regulation of Akt, the overexpression of wild-type or catalytically
      inactive PLIP in Chinese hamster ovary-insulin receptor cells or a dsRNA-mediated
      knockdown of PLIP mRNA levels in Drosophila S2 cells does not alter Akt activity
      or phosphorylation. The unique in vitro catalytic activity and detailed
      biochemical and kinetic analyses reported here will be of great value in our
      continued efforts to identify in vivo substrate(s) for this highly conserved
      phosphatase.

PMID- 15247230
TI  - Differential regulation of membrane type 1-matrix metalloproteinase activity by
      ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2
      expression controls transforming growth factor-beta1-induced pericellular
      collagenolysis.
AB  - Acquisition of matrix metalloproteinase-2 (MMP-2) activity is temporally
      associated with increased migration and invasiveness of cancer cells. ProMMP-2
      activation requires multimolecular complex assembly involving proMMP-2, membrane
      type 1-MMP (MT1-MMP, MMP-14), and tissue inhibitor of metalloproteinases-2 (TIMP
      2). Because transforming growth factor-beta1 (TGF-beta1) promotes tumor invasion
      in advanced squamous cell carcinomas, the role of TGF-beta1 in the regulation of
      MMP activity in a cellular model of invasive oral squamous cell carcinoma was
      examined. Treatment of oral squamous cell carcinoma cells with TGF-beta1 promoted
      MMP-dependent cell scattering and collagen invasion, increased expression of MMP
      2 and MT1-MMP, and enhanced MMP-2 activation. TGF-beta1 induced concomitant
      activation of ERK1/2 and p38 MAPK, and kinase inhibition studies revealed a
      negative regulatory role for ERK1/2 in modulating acquisition of MMP-2 activity.
      Thus, a reciprocal effect on proMMP-2 activation was observed whereupon blocking
      ERK1/2 phosphorylation promoted proMMP-2 activation and MT1-MMP activity, whereas
      inhibiting p38 MAPK activity decreased proteolytic potential. The cellular
      mechanism for the control of MT1-MMP catalytic activity involved concurrent
      reciprocal modulation of TIMP-2 expression by ERK1/2 and p38 MAPKs, such that
      inhibition of ERK1/2 phosphorylation decreased TIMP-2 production, and down
      regulation of p38 MAPK activity enhanced TIMP-2 synthesis. Further, p38 MAPK
      inhibition promoted ERK1/2 phosphorylation, providing additional evidence for
      cross-talk between MAPK pathways. These observations demonstrate the complex
      reciprocal effects of ERK1/2 and p38 MAPK in the regulation of MMP activity,
      which could complicate the use of MAPK-specific inhibitors as therapeutic agents
      to down-regulate the biologic effects of TGF-beta1 on pericellular collagen
      degradation and tumor invasion.

PMID- 15247231
TI  - SNARE assembly and membrane fusion, a kinetic analysis.
AB  - SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)
      assembly may promote intracellular membrane fusion, an essential process for
      vesicular transport in cells. Core complex formation between vesicle-associated
      SNARE and target membrane SNARE perhaps drives the merging of two membranes into
      a single bilayer. Using spin-labeling EPR, trans-SNARE complex formation was
      monitored "locally" at four different core locations of recombinant yeast SNAREs,
      which are individually reconstituted into phospholipid vesicles. The results
      indicate that the time scales of core formation are virtually the same at all
      four locations throughout the core region, indicating the possibility of a single
      step core assembly, which appears to be somewhat different from what has been
      postulated by the "zipper" model. The EPR data were then compared with the
      kinetics of the lipid mixing measured with the fluorescence assay. The analysis
      suggests that SNARE core assembly occurs on a much faster time scale than the
      lipid mixing, providing a new insight into the timing of individual events in
      SNARE-induced membrane fusion.

PMID- 15247232
TI  - Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the
      regulation of hypoxia-inducible factor.
AB  - Hypoxia-inducible factor (HIF) is a transcriptional regulator that plays a key
      role in many aspects of oxygen homeostasis. The heterodimeric HIF complex is
      regulated by proteolysis of its alpha-subunits, following oxygen-dependent
      hydroxylation of specific prolyl residues. Although three HIF prolyl
      hydroxylases, PHD1, PHD2, and PHD3, have been identified that have the potential
      to catalyze this reaction, the contribution of each isoform to the physiological
      regulation of HIF remains uncertain. Here we show using suppression by small
      interference RNA that each of the three PHD isoforms contributes in a non
      redundant manner to the regulation of both HIF-1alpha and HIF-2alpha subunits and
      that the contribution of each PHD under particular culture conditions is strongly
      dependent on the abundance of the enzyme. Thus in different cell types, isoform
      specific patterns of PHD induction by hypoxia and estrogen alter both the
      relative abundance of the PHDs and their relative contribution to the regulation
      of HIF. In addition, the PHDs manifest specificity for different prolyl
      hydroxylation sites within each HIF-alpha subunit, and a degree of selectively
      between HIF-1alpha and HIF-2alpha isoforms, indicating that differential PHD
      inhibition has the potential to selectively alter the characteristics of HIF
      activation.

PMID- 15247233
TI  - Purification and crystallization of the cystic fibrosis transmembrane conductance
      regulator (CFTR).
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane
      protein that is mutated in patients suffering from cystic fibrosis. Here we
      report the purification and first crystallization of wild-type human CFTR.
      Functional characterization of the material showed it to be highly active.
      Electron crystallography of negatively stained two-dimensional crystals of CFTR
      has revealed the overall architecture of this channel for two different
      conformational states. These show a strong structural homology to two
      conformational states of another eukaryotic ATP-binding cassette transporter, P
      glycoprotein. In contrast to P-glycoprotein, however, both conformational states
      can be observed in the presence of a nucleotide, which may be related to the role
      of CFTR as an ion channel rather than a transporter. The hypothesis that the two
      conformations could represent the "open" and "closed" states of the channel is
      considered.

PMID- 15247234
TI  - Selective regulation of acid-sensing ion channel 1 by serine proteases.
AB  - Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the
      epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a
      rapid drop in extracellular pH. Conditions of low extracellular pH, such as
      ischemia and inflammation in which ASICs are thought to be active, are
      accompanied by increased protease activity. We show here that serine proteases
      modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show
      that protease exposure shifts the pH dependence of ASIC1a activation and steady
      state inactivation to more acidic pH. As a consequence, protease exposure leads
      to a decrease in current response if ASIC1a is activated by a pH drop from pH
      7.4. If, however, acidification occurs from a basal pH of approximately 7,
      protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide
      evidence that this bi-directional regulation of ASIC1a function also occurs in
      neurons. Thus, we have identified a mechanism that modulates ASIC function and
      may allow ASIC1a to adapt its gating to situations of persistent extracellular
      acidification.

PMID- 15247235
TI  - NPR1 kinase and RSP5-BUL1/2 ubiquitin ligase control GLN3-dependent transcription
      in Saccharomyces cerevisiae.
AB  - The GATA transcription factors GLN3 and GAT1 activate nitrogen-regulated genes in
      Saccharomyces cerevisiae. NPR1 is a protein kinase that controls post-Golgi
      sorting of amino acid permeases. In the presence of a good nitrogen source, TOR
      (target of rapamycin) maintains GLN3 and NPR1 phosphorylated and inactive by
      inhibiting the type 2A-related phosphatase SIT4. We identified NPR1 as a
      regulator of GLN3. Specifically, loss of NPR1 causes nuclear translocation and
      activation of GLN3, but not GAT1, in nitrogen-rich conditions. NPR1-mediated
      inhibition of GLN3 is independent of the phosphatase SIT4. We also demonstrate
      that the E3/E4 ubiquitin-protein ligase proteins RSP5 and BUL1/2 are required for
      GLN3 activation under poor nitrogen conditions. Thus, NPR1 and BUL1/2
      antagonistically control GLN3-dependent transcription, suggesting a role for
      regulated ubiquitination in the control of nutrient-responsive transcription.

PMID- 15247236
TI  - Involvement of the molybdenum cofactor biosynthetic machinery in the maturation
      of the Escherichia coli nitrate reductase A.
AB  - The maturation of Escherichia coli nitrate reductase A requires the incorporation
      of the Mo-(bis-MGD) cofactor to the apoprotein. For this process, the NarJ
      chaperone is strictly required. We report the first description of protein
      interactions between molybdenum cofactor biosynthetic proteins (MogA, MoeA, MobA,
      and MobB) and the aponitrate reductase (NarG) using a bacterial two-hybrid
      approach. Two conditions have to be satisfied to allow the visualization of the
      interactions, (i) the presence of an active and mature molybdenum cofactor and
      (ii) the presence of the NarJ chaperone and of the NarG structural partner
      subunit, NarH. Formation of tungsten-substituted cofactor prevents the
      interaction between NarG and the four biosynthetic proteins. Our results
      suggested that the final stages of molybdenum cofactor biosynthesis occur on a
      complex made up by MogA, MoeA, MobA, and MobB, which is also in charge with the
      delivery of the mature cofactor onto the aponitrate reductase A in a NarJ
      assisted process.

PMID- 15247237
TI  - Structural and thermodynamic characterization of Pal, a phage natural chimeric
      lysin active against pneumococci.
AB  - Pal amidase, encoded by pneumococcal bacteriophage Dp-1, represents one step
      beyond in the modular evolution of pneumococcal murein hydrolases. It exhibits
      the choline-binding module attaching pneumococcal lysins to the cell wall, but
      the catalytic module is different from those present in the amidases coded by the
      host or other pneumococcal phages. Pal is also an effective antimicrobial agent
      against Streptococcus pneumoniae that may constitute an alternative to antibiotic
      prophylaxis. The structural implications of Pal singular structure and their
      effect on the choline-amidase interactions have been examined by means of several
      techniques. Pal stability is maximum around pH 8.0 (Tm approximately 50.2 degrees
      C; DeltaHt = 183 +/- 4 kcal mol(-1)), and its constituting modules fold as two
      tight interacting cooperative units whose denaturation merges into a single
      process in the free amidase but may proceed as two well resolved events in the
      choline-bound state. Choline titration curves reflect low energy ligand-protein
      interactions and are compatible with two sets of sites. Choline binding strongly
      stabilizes the cell wall binding module, and the conformational stabilization is
      transmitted to the catalytic region. Moreover, the high proportion of aggregates
      formed by the unbound amidase together with choline preferential interaction with
      Pal dimers suggest the existence of marginally stable regions that would become
      stabilized through choline-protein interactions without significantly modifying
      Pal secondary structure. This structural rearrangement may underlie in vitro
      "conversion" of Pal from the low to the full activity form triggered by choline.
      The Pal catalytic module secondary structure could denote folding conservation
      within pneumococcal lytic amidases, but the number of functional choline binding
      sites is reduced (2-3 sites per monomer) when compared with pneumococcal LytA
      amidase (4-5 sites per monomer) and displays different intermodular interactions.

PMID- 15247238
TI  - Uth1p is involved in the autophagic degradation of mitochondria.
AB  - The absence of the outer mitochondrial membrane protein Uth1p was found to induce
      resistance to rapamycin treatment and starvation, two conditions that induce the
      autophagic process. Biochemical studies showed the onset of a fully active
      autophagic activity both in wild-type and Deltauth1 strains. On the other hand,
      the disorganization of the mitochondrial network induced by rapamycin treatment
      or 15 h of nitrogen starvation was followed in cells expressing mitochondria
      targeted green fluorescent protein; a rapid colocalization of green fluorescent
      protein fluorescence with vacuole-selective FM4-64 labeling was observed in the
      wild-type but not in the Deltauth1 strain. Degradation of mitochondrial proteins,
      followed by Western blot analysis, did not occur in mutant strains carrying null
      mutations of the vacuolar protease Pep4p, the autophagy-specific protein Atg5p,
      and Uth1p. These data show that, although the autophagic machinery was fully
      functional in the absence of Uth1p, this protein is involved in the autophagic
      degradation of mitochondria.

PMID- 15247239
TI  - Endo-beta-mannosidase, a plant enzyme acting on N-glycan: purification, molecular
      cloning, and characterization.
AB  - Endo-beta-mannosidase is a novel endoglycosidase that hydrolyzes the Manbeta1
      4GlcNAc linkage in the trimannosyl core structure of N-glycans. This enzyme was
      partially purified and characterized in a previous report (Sasaki, A., Yamagishi,
      M., Mega, T., Norioka, S., Natsuka, S., and Hase, S. (1999) J. Biochem. 125, 363
      367). Here we report the purification and molecular cloning of endo-beta
      mannosidase. The enzyme purified from lily flowers gave a single band on native
      PAGE and three bands on SDS-PAGE with molecular masses of 42, 31, and 28 kDa.
      Amino acid sequence information from these three polypeptides allowed the cloning
      of a homologous gene, AtEBM, from Arabidopsis thaliana. AtEBM was engineered for
      expression in Escherichia coli, and the recombinant protein comprised a single
      polypeptide chain with a molecular mass of 112 kDa corresponding to the sum of
      molecular masses of three polypeptides of the lily enzyme. The recombinant
      protein hydrolyzed pyridylamino derivatives (PA) of Manalpha1-6Manbeta1-4Glc
      NAcbeta1-4GlcNAc into Manalpha1-6Man and GlcNAcbeta1-4Glc-NAc-PA, showing that
      AtEBM is an endo-beta-mannosidase. AtEBM hydrolyzed Man(n)Manalpha1-6Manbeta1
      4GlcNAcbeta1-4GlcNAc-PA (n = 0-2) but not PA-sugar chains containing Manalpha1
      3Manbeta or Xylosebeta1-2Manbeta as for the lily endo-beta-mannosidase. AtEBM
      belonged to the clan GH-A of glycosyl hydrolases. Site-directed mutagenesis
      experiments revealed that two glutamic acid residues (Glu-464 and Glu-549)
      conserved in this clan were critical for enzyme activity. The amino acid sequence
      of AtEBM has distinct differences from those of the bacterial, fungal, and animal
      exo-type beta-mannosidases. Indeed, AtEBM-like genes are only found in plants,
      indicating that endo-beta-mannosidase is a plant-specific enzyme. The role of
      this enzyme in the processing and/or degradation of N-glycan will be discussed.

PMID- 15247240
TI  - The transcriptional responses of Mycobacterium tuberculosis to inhibitors of
      metabolism: novel insights into drug mechanisms of action.
AB  - The differential transcriptional response of Mycobacterium tuberculosis to drugs
      and growth-inhibitory conditions was monitored to generate a data set of 430
      microarray profiles. Unbiased grouping of these profiles independently clustered
      agents of known mechanism of action accurately and was successful at predicting
      the mechanism of action of several unknown agents. These predictions were
      validated biochemically for two agents of previously uncategorized mechanism,
      pyridoacridones and phenothiazines. Analysis of this data set further revealed
      150 underlying clusters of coordinately regulated genes offering the first
      glimpse at the full metabolic potential of this organism. A signature subset of
      these gene clusters was sufficient to classify all known agents as to mechanism
      of action. Transcriptional profiling of both crude and purified natural products
      can provide critical information on both mechanism and detoxification prior to
      purification that can be used to guide the drug discovery process. Thus, the
      transcriptional profile generated by a crude marine natural product recapitulated
      the mechanistic prediction from the pure active component. The underlying gene
      clusters further provide fundamental insights into the metabolic response of
      bacteria to drug-induced stress and provide a rational basis for the selection of
      critical metabolic targets for screening for new agents with improved activity
      against this important human pathogen.

PMID- 15247241
TI  - Crystallographic and mutational data show that the streptococcal pyrogenic
      exotoxin J can use a common binding surface for T-cell receptor binding and
      dimerization.
AB  - The protein toxins known as superantigens (SAgs), which are expressed primarily
      by the pathogenic bacteria Staphylococcus aureus and Streptococcus pyogenes, are
      highly potent immunotoxins with the ability to cause serious human disease. These
      SAgs share a conserved fold but quite varied activities. In addition to their
      common role of cross-linking T-cell receptors (TCRs) and major histocompatibility
      complex class II (MHC-II) molecules, some SAgs can cross-link MHC-II, using
      diverse mechanisms. The crystal structure of the streptococcal superantigen
      streptococcal pyrogenic exotoxin J (SPE-J) has been solved at 1.75 A resolution
      (R = 0.209, R(free) = 0.240), both with and without bound Zn(2+). The structure
      displays the canonical two-domain SAg fold and a zinc-binding site that is shared
      by a subset of other SAgs. Most importantly, in concentrated solution and in the
      crystal, SPE-J forms dimers. These dimers, which are present in two different
      crystal environments, form via the same face that is used for TCR binding in
      other SAgs. Site-directed mutagenesis shows that this face is also used for TCR
      binding SPE-J. We infer that SPE-J cross-links TCR and MHC-II as a monomer but
      that dimers may form on the antigen-presenting cell surface, cross-linking MHC-II
      and eliciting intracellular signaling.

PMID- 15247242
TI  - Regulation of intercellular adhesion strength in fibroblasts.
AB  - The regulation of adherens junction formation in cells of mesenchymal lineage is
      of critical importance in tumorigenesis but is poorly characterized. As actin
      filaments are crucial components of adherens junction assembly, we studied the
      role of gelsolin, a calcium-dependent, actin severing protein, in the formation
      of N-cadherin-mediated intercellular adhesions. With a homotypic, donor-acceptor
      cell model and plates or beads coated with recombinant N-cadherin-Fc chimeric
      protein, we found that gelsolin spatially co-localizes to, and is transiently
      associated with, cadherin adhesion complexes. Fibroblasts from gelsolin-null mice
      exhibited marked reductions in kinetics and strengthening of N-cadherin-dependent
      junctions when compared with wild-type cells. Experiments with lanthanum chloride
      (250 microm) showed that adhesion strength was dependent on entry of calcium ions
      subsequent to N-cadherin ligation. Cadherin-associated gelsolin severing activity
      was required for localized actin assembly as determined by rhodamine actin
      monomer incorporation onto actin barbed ends at intercellular adhesion sites.
      Scanning electron microscopy showed that gelsolin was an important determinant of
      actin filament architecture of adherens junctions at nascent N-cadherin-mediated
      contacts. These data indicate that increased actin barbed end generation by the
      severing activity of gelsolin associated with N-cadherin regulates intercellular
      adhesion strength.

PMID- 15247243
TI  - Phosphorylation of rat liver mitochondrial carnitine palmitoyltransferase-I:
      effect on the kinetic properties of the enzyme.
AB  - Hepatic carnitine palmitoyltransferase-I (CPT-IL) isolated from mitochondrial
      outer membranes obtained in the presence of protein phosphatase inhibitors is
      readily recognized by phosphoamino acid antibodies. Mass spectrometric analysis
      of CPT-IL tryptic digests revealed the presence of three phosphopeptides
      including one with a protein kinase CKII (CKII) consensus site. Incubation of
      dephosphorylated outer membranes with protein kinases and [gamma-32P]ATP resulted
      in radiolabeling of CPT-I only by CKII. Using mass spectrometry, only one region
      of phosphorylation was detected in CPT-I isolated from CKII-treated mitochondria.
      The sequence of the peptide and position of phosphorylated amino acids have been
      determined unequivocally as FpSSPETDpSHRFGK (residues 740-752). Furthermore,
      incubation of dephosphorylated outer membranes with CKII and unlabeled ATP led to
      increased catalytic activity and rendered malonyl-CoA inhibition of CPT-I from
      competitive to uncompetitive. These observations identify a new mechanism for
      regulation of hepatic CPT-I by phosphorylation.

PMID- 15247244
TI  - Utility of acetyldithio-CoA in detecting the influence of active site residues on
      substrate enolization by 3-hydroxyl-3-methylglutaryl-CoA synthase.
AB  - Hydroxymethylglutaryl-CoA synthase-catalyzed condensation of acetyl-CoA with
      acetoacetyl-CoA requires enolization/carbanion formation from the acetyl C-2
      methyl group prior to formation of a new carbon-carbon bond. Acetyldithio-CoA, a
      readily enolizable analog of acetyl-CoA, was an effective competitive inhibitor
      of avian hydroxymethylglutaryl-CoA synthase (Ki = 28 microm). In the absence of
      cosubstrate, enzyme catalyzed the enolization/proton exchange from the C-2 methyl
      group of acetyldithio-CoA. Mutant enzymes that exhibited impaired formation of
      the covalent acetyl-S-enzyme reaction intermediate exhibited diminished (D159A
      and D203A) or undetectable (C129S) rates of enolization of acetyldithio-CoA. The
      results suggest that covalent thioacetylation of protein, which has not been
      detected previously for other enzymes that enolize this analog, occurs with
      hydroxymethylglutaryl-CoA synthase. Enzyme catalyzed the transfer of the
      thioacetyl group of this analog to 3'-dephospho-CoA suggesting the intermediacy
      of a covalent thioacetyl-S-enzyme species, which appears to be important for
      proton abstraction from C-2 of the thioacetyl group. Avian enzyme glutamate 95 is
      crucial to substrate condensation to form a new carboncarbon bond. Mutations of
      this invariant residue (avian enzyme E95A and E95Q; Staphylococcus aureus enzyme
      E79Q) correlated with diminished ability to catalyze enolization of acetyldithio
      CoA. Enolization by E95Q was not stimulated in the presence of acetoacetyl-CoA.
      These observations suggest either a direct (proton abstraction) or indirect
      (solvent polarization) role for this active site glutamate.

PMID- 15247245
TI  - Crystal structure of the endonuclease domain encoded by the telomere-specific
      long interspersed nuclear element, TRAS1.
AB  - The telomere-specific long interspersed nuclear element, TRAS1, encodes an
      endonuclease domain, TRAS1-EN, which specifically cleaves the telomeric repeat
      targets (TTAGG)n of insects and (TTAGGG)n of vertebrates. To elucidate the
      sequence-specific recognition properties of TRAS1-EN, we determined the crystal
      structure at 2.4-A resolution. TRAS1-EN has a four-layered alpha/beta sandwich
      structure; its topology is similar to apurinic/apyrimidinic endonucleases, but
      the beta-hairpin (beta10-beta11) at the edge of the DNA-binding surface makes an
      extra loop that distinguishes TRAS1-EN from cellular apurinic/apyrimidinic
      endonucleases. A protein-DNA complex model suggests that the beta10-beta11
      hairpin fits into the minor groove, enabling interaction with the telomeric
      repeats. Mutational studies of TRAS1-EN also indicated that the Asp-130 and
      beta10-beta11 hairpin structure are involved in specific recognition of telomeric
      repeats.

PMID- 15247246
TI  - O-GlcNAc transferase is in a functional complex with protein phosphatase 1
      catalytic subunits.
AB  - A hallmark of signal transduction is the dynamic and inducible post-translational
      modification of proteins. In addition to the well characterized phosphorylation
      of proteins, other modifications have been shown to be regulatory, including O
      linked beta-N-acetylglucosamine (O-GlcNAc). O-GlcNAc modifies serine and
      threonine residues on a myriad of nuclear and cytosolic proteins, and for several
      proteins there appears to be a reciprocal relationship between phosphorylation
      and O-GlcNAc modification. Here we report further evidence of this yin-yang
      relationship by demonstrating that O-GlcNAc transferase, the enzyme that adds O
      GlcNAc to proteins, exists in stable and active complexes with the
      serine/threonine phosphatases PP1beta and PP1gamma, enzymes that remove phosphate
      from proteins. The existence of this complex highlights the importance of
      understanding the dynamic relationship between O-GlcNAc and phosphate in
      modulating protein function in many cellular processes and disease states such as
      Alzheimer's disease and type II diabetes.

PMID- 15247247
TI  - Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in
      CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of
      the cell cycle.
AB  - Phosphatidylcholine is the major lipid component in mammalian membranes.
      Phosphatidylcholine synthesis increases in C3H10T1/2 fibroblasts during the G(1)
      and S phases of the cell cycle. Previous studies demonstrated that the mRNA
      encoding CTP:phosphocholine cytidylyltransferase alpha (CTalpha) increases during
      S phase (Golfman, L. S., Bakovic, M., and Vance, D. E. (2001) J. Biol. Chem. 276,
      43688-43692) and that this activation is driven by increased binding of Sp1 to
      the CTalpha promoter (Banchio, C., Schang, L. M., and Vance, D. E. (2003) J.
      Biol. Chem. 278, 32457-32464). We now demonstrate that cyclin-dependent kinase 2
      (CDK2) phosphorylation of Sp1 activates CTalpha transcription during S phase. Sp1
      binds in a phosphorylated state to the CTalpha promoter. Sp1 binding is enhanced
      by association with cyclin A/E and CDK2, both in vivo and in vitro. In cells that
      overexpress Sp1, co-expression of cyclin A and CDK2 induces a high and constant
      level of CTalpha expression, whereas reduction in the expression of cyclin A,
      cyclin E, and CDK2 eliminates the induction of CTalpha expression in S phase.
      Furthermore, CTalpha expression is decreased in cells overexpressing a dominant
      negative form of CDK2 and in cells treated with the CDK2 kinase inhibitors
      roscovitine and olomoucine. These results enhance our understanding of the
      regulatory mechanisms involved in the expression of CTalpha in preparation for
      cell division.

PMID- 15247248
TI  - Isolation of mutant cells lacking Insig-1 through selection with SR-12813, an
      agent that stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase.
AB  - Insig-1 and Insig-2 are membrane proteins of the endoplasmic reticulum that
      regulate lipid metabolism by the following two actions: 1) sterol-induced binding
      to 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an action that leads to
      ubiquitination and degradation of the enzyme; and 2) sterol-induced binding to
      SREBP cleavage-activating protein, an action that blocks the proteolytic
      processing of sterol regulatory element-binding proteins (SREBPs), membrane-bound
      transcription factors that enhance the synthesis of cholesterol and fatty acids.
      Here we report the isolation of a new mutant line of Chinese hamster ovary cells,
      designated SRD-14, in which Insig-1 mRNA and protein are not produced due to a
      partial deletion of the INSIG-1 gene. The SRD-14 cells were produced by gamma
      irradiation, followed by selection with the 1,1-bisphosphonate ester SR-12813,
      which mimics sterols in accelerating reductase degradation but does not block
      SREBP processing. SRD-14 cells fail to respond to sterols by promoting reductase
      ubiquitination and degradation. The rate at which sterols suppress SREBP
      processing is significantly slower in SRD-14 cells than wild type CHO-7 cells.
      Sterol regulation of reductase degradation and SREBP processing is restored when
      SRD-14 cells are transfected with expression plasmids encoding either Insig-1 or
      Insig-2. These results provide formal genetic proof for the essential role of
      Insig-1 in feedback control of lipid synthesis in cultured cells.

PMID- 15247250
TI  - The role of subtype-specific ligand binding and the C-tail domain in dimer
      formation of human somatostatin receptors.
AB  - G-protein-coupled receptors (GPCRs) represent the largest and most diverse family
      of cell surface receptors. Several GPCRs have been documented to dimerize with
      resulting changes in pharmacology. We have previously reported by means of
      photobleaching fluorescence resonance energy transfer (pbFRET) microscopy and
      fluorescence correlation spectroscopic (FCS) analysis in live cells, that human
      somatostatin receptor (hSSTR) 5 could both homodimerize and heterodimerize with
      hSSTR1 in the presence of the agonist SST-14. In contrast, hSSTR1 remained
      monomeric when expressed alone regardless of agonist exposure in live cells. In
      an effort to elucidate the role of ligand and receptor subtypes in
      heterodimerization, we have employed both pb-FRET microscopy and Western blot on
      cells stably co-expressing hSSTR1 and hSSTR5 treated with subtype-specific
      agonists. Here we provide evidence that activation of hSSTR5 but not hSSTR1 is
      necessary for heterodimeric assembly. This property was also reflected in
      signaling as shown by increases in adenylyl cyclase coupling efficiencies.
      Furthermore, receptor C-tail chimeras allowed for the identification of the C
      tail as a determinant for dimerization. Finally, we demonstrate that
      heterodimerization is subtype-selective involving ligand-induced conformational
      changes in hSSTR5 but not hSSTR1 and could be attributed to molecular events
      occurring at the C-tail. Understanding the mechanisms by which GPCRs dimerize
      holds promise for improvements in drug design and efficacy.

PMID- 15247249
TI  - Regulation of hepatitis C virus polyprotein processing by signal peptidase
      involves structural determinants at the p7 sequence junctions.
AB  - The hepatitis C virus genome encodes a polyprotein precursor that is co- and post
      translationally processed by cellular and viral proteases to yield 10 mature
      protein products (C, E1, E2, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Although
      most cleavages in hepatitis C virus polyprotein precursor proceed to completion
      during or immediately after translation, the cleavages mediated by a host cell
      signal peptidase are partial at the E2/p7 and p7/NS2 sites, leading to the
      production of an E2p7NS2 precursor. The sequences located immediately N
      terminally of E2/p7 and p7/NS2 cleavage sites can function as signal peptides.
      When fused to a reporter protein, the signal peptides of p7 and NS2 were
      efficiently cleaved. However, when full-length p7 was fused to the reporter
      protein, partial cleavage was observed, indicating that a sequence located N
      terminally of the signal peptide reduces the efficiency of p7/NS2 cleavage.
      Sequence analyses and mutagenesis studies have also identified structural
      determinants responsible for the partial cleavage at both the E2/p7 and p7/NS2
      sites. Finally, the short distance between the cleavage site of E2/p7 or p7/NS2
      and the predicted transmembrane alpha-helix within the P' region might impose
      additional structural constraints to the cleavage sites. The insertion of a
      linker polypeptide sequence between P-3' and P-4' of the cleavage site released
      these constraints and led to improved cleavage efficiency. Such constraints in
      the processing of a polyprotein precursor are likely essential for hepatitis C
      virus to post-translationally regulate the kinetics and/or the level of
      expression of p7 as well as NS2 and E2 mature proteins.

PMID- 15247251
TI  - Calcineurin Aalpha but not Abeta augments ICl(Ca) in rabbit pulmonary artery
      smooth muscle cells.
AB  - Activation of Ca(2+)-dependent Cl(-) currents (I(Cl(Ca))) increases membrane
      excitability in vascular smooth muscle cells. Previous studies showed that Ca(2+)
      dependent phosphorylation suppresses I(Cl(Ca)) in pulmonary artery myocytes, and
      the aim of the present study was to determine the role of the Ca(2+)-dependent
      phosphatase calcineurin on chloride channel activity. Immunocytochemical and
      Western blot studies with isoform-specific antibodies revealed that the alpha and
      beta forms of the CaN catalytic subunit are expressed in PA cells but that only
      the alpha variant translocated to the cell periphery upon a rise in intracellular
      [Ca(2+)]. I(Cl(Ca)) evoked by pipette solutions containing a [Ca(2+)] set at 500
      nm was considerably larger when the pipette solution included constitutively
      active CaN containing the alpha catalytic isoform. This stimulatory effect was
      lost by boiling the enzyme or by the inclusion of a specific CaN inhibitory
      peptide and was not shared by the inclusion of the beta form of the catalytic
      subunit. In the absence of constitutively active CaN, cyclosporin A, an inhibitor
      of CaN, suppressed I(Cl(Ca)) evoked by 500 nm Ca(2+) when the current amplitude
      was relatively large but was ineffective in cells with smaller currents. In
      perforated patch recordings, cyclosporin A consistently inhibited I(Cl(Ca))
      evoked as a consequence of Ca(2+) influx through voltage-dependent calcium
      channels. These novel data show that in PA myocytes activation of I(Cl(Ca)) is
      enhanced by Ca(2+)-dependent dephosphorylation and that the regulation of this
      conductance is highly isoform-specific.

PMID- 15247252
TI  - Insights into the oligomeric states, conformational changes, and helicase
      activities of SV40 large tumor antigen.
AB  - The large T (LT) antigen encoded by SV40 virus is a multi-domain, multi
      functional protein that can not only transform cells but can also function as an
      efficient molecular machine to unwind duplex DNA for DNA replication. Here we
      report our findings on the oligomeric forms, domain interactions, and ATPase and
      helicase activities of various LT constructs. For the LT constructs that
      hexamerize, only two oligomeric forms, hexameric and monomeric, were detected in
      the absence of ATP/ADP. However, the presence of ATP/ADP stabilizes LT in the
      hexameric form. The LT constructs lacking the N- and C-terminal domains, but
      still retaining hexamerization ability, have ATPase as well as helicase
      activities at a level comparable to the full-length LT, suggesting the importance
      of hexamerization for these activities. The domain structures and the possible
      interactions between different LT fragments were probed with limited protease
      (trypsin) digestion. Such protease digestion generated a distinct pattern in the
      presence and absence of ATP/ADP and Mg(2+). The most C-terminal fragment
      (residues 628-708, containing the host-range domain), which was thought to be
      completely unstructured, was somewhat trypsin-resistant despite the presence of
      multiple Arg and Lys, possibly due to a rather structured C terminus.
      Furthermore, the N- and C-terminal fragments cleaved by trypsin were associated
      with other parts of the molecule, suggesting the interdomain interactions for the
      fragments at both ends.

PMID- 15247253
TI  - Partial proteolysis of simian virus 40 T antigen reveals intramolecular contacts
      between domains and conformation changes upon hexamer assembly.
AB  - Simian virus 40 large tumor antigen (Tag) is a multi-functional viral protein
      that binds specifically to SV40 origin DNA, serves as the replicative DNA
      helicase, and orchestrates the assembly and operation of the viral replisome. Tag
      associated with Mg-ATP forms hexamers and, in the presence of SV40 origin DNA,
      double hexamers. Limited tryptic digestion of monomeric Tag revealed three major
      stable structural domains. The N-terminal domain spans amino acids 1-130, the
      central domain comprises amino acids 131-476, and the C-terminal domain extends
      from amino acid 513 to amino acid 698. Co-immunoprecipitation of digestion
      products of monomeric Tag suggests that the N-terminal domain associates stably
      with sequences located in the central region of the same Tag molecule. Hexamer
      formation protected the tryptic cleavage sites in the exposed region between the
      central and C-terminal domains. Upon hexamerization, this exposed region also
      became less accessible to a monoclonal antibody whose epitope maps in that
      region. The tryptic digestion products of the soluble hexamer and the DNA-bound
      double hexamer were indistinguishable. A low-resolution model of the
      intramolecular and intermolecular interactions among Tag domains in the double
      hexamer is proposed.

PMID- 15247254
TI  - Homo-oligomerization of ALS2 through its unique carboxyl-terminal regions is
      essential for the ALS2-associated Rab5 guanine nucleotide exchange activity and
      its regulatory function on endosome trafficking.
AB  - Mutations in the ALS2 gene have been known to account for a juvenile recessive
      form of amyotrophic lateral sclerosis (ALS2), a rare juvenile recessive form of
      primary lateral sclerosis, and a form of hereditary spastic paraplegia (HSP),
      indicating that the ALS2 protein is essential for the maintenance of motor
      neurons. Recently, we have demonstrated that the ALS2 protein specifically binds
      to the small GTPase Rab5 and acts as a GEF (guanine nucleotide exchange factor)
      for Rab5. We have also shown that its Rab5GEF-requisite domain resides within the
      C-terminal 640-amino acid region spanning membrane occupation and recognition
      nexus motifs and the vacuolar protein sorting 9 domain. Transiently expressed
      ALS2 localized onto early endosomal compartments and stimulated endosome fusions
      in neuronal and non-neuronal cells in an Rab5GEF activity-dependent manner. These
      results indicate that the C-terminal region of ALS2 plays a crucial role in
      endosomal dynamics by its Rab5GEF activity. Here we delineate a molecular feature
      of the ALS2-associated function through the C-terminal region-mediated homo
      oligomerization. A yeast two-hybrid screen for interacting proteins with the ALS2
      C-terminal portion identified ALS2 itself. ALS2 forms a homophilic oligomer
      through its distinct C-terminal regions. This homo-oligomerization is crucial for
      the Rab5GEF activity in vitro and the ALS2-mediated endosome enlargement in the
      cells. Taken together, these results indicate that oligomerization of the ALS2
      protein is one of the fundamental features for its physiological function
      involving endosome dynamics in vivo.

PMID- 15247255
TI  - Fibroblast growth factor-2 induction of platelet-derived growth factor-C chain
      transcription in vascular smooth muscle cells is ERK-dependent but not JNK
      dependent and mediated by Egr-1.
AB  - Platelet-derived growth factors (PDGFs) play an integral role in normal tissue
      growth and maintenance as well as many human pathological states including
      atherosclerosis, fibrosis, and tumorigenesis. The PDGF family of ligands is
      comprised of A, B, C, and D chains. Here, we provide the first functional
      characterization of the PDGF-C promoter. We examined 797 bp of the human PDGF-C
      promoter and identified several putative recognition elements for Sp1, Ets Egr-1,
      and Smad. The proximal region of the PDGF-C promoter bears a remarkable
      resemblance to a comparable region of the PDGF-A promoter (1). Binding and
      transient transfection analysis in primary vascular smooth muscle cells revealed
      that PDGF-C, like PDGF-A, is under the transcriptional control of the zinc finger
      nuclear protein Egr-1 (early growth response-1). Electrophoretic mobility shift
      analysis using both smooth muscle cell nuclear extracts and recombinant protein
      revealed that Egr-1 and Sp1 bind this region of the PDGF-C promoter (Oligo C, -35
      to -1). Egr-1 competes with Sp1 for overlapping binding sites even when the
      former is at a stoichiometric disadvantage. Reverse transcriptase PCR and
      supershift analysis demonstrate that fibroblast growth factor-2 (FGF-2)
      stimulates both Egr-1 and PDGF-C mRNA expression in a time-dependent and
      transient manner and that FGF-2-inducible Egr-1 binds the proximal PDGF-C
      promoter. FGF-2-inducible PDGF-C expression was completely abrogated using
      catalytic DNA (DNAzymes) targeting Egr-1 but not by its scrambled counterpart.
      Moreover, using pharmacological inhibitors we demonstrate the critical role of
      ERK but not JNK in FGF-2-inducible PDGF-C expression. These findings thus
      demonstrate that PDGF-C transcription, activated by FGF-2, is mediated by Egr-1
      and its upstream kinase ERK.

PMID- 15247256
TI  - NMR solution structure of Ole e 6, a major allergen from olive tree pollen.
AB  - Ole e 6 is a pollen protein from the olive tree (Olea europaea) that exhibits
      allergenic activity with a high prevalence among olive-allergic individuals. The
      three-dimensional structure of Ole e 6 has been determined in solution by NMR
      methods. This is the first experimentally determined structure of an olive tree
      pollen allergen. The structure of this 50-residue protein is based on 486 upper
      limit distance constraints derived from nuclear Overhauser effects and 24 torsion
      angle restraints. The global fold of Ole e 6 consists of two nearly antiparallel
      alpha-helices, spanning residues 3-19 and 23-33, that are connected by a short
      loop and followed by a long, unstructured C-terminal tail. Viewed edge-on, the
      structured N terminus has a dumbbell-like shape with the two helices on the
      outside and with the hydrophobic core, mainly composed of 3 aromatic and 6
      cysteine residues, on the inside. All the aromatic rings lie on top of and pack
      against the three disulfide bonds. The lack of thermal unfolding, even at 85
      degrees C, indicates a high conformational stability. Based on the analysis of
      the molecular surface, we propose five plausible epitopes for IgE recognition.
      The results presented here provide the structural foundation for future
      experiments to verify the antigenicity of the proposed epitopes, as well as to
      design novel hypoallergenic forms of the protein suitable for diagnosis and
      treatment of type-I allergies. In addition, three-dimensional structure features
      of Ole e 6 are discussed to provide a basis for future functional studies.

PMID- 15247257
TI  - Helix induction in antimicrobial peptides by alginate in biofilms.
AB  - Bacterial exopolysaccharides provide protection against phagocytosis,
      opsonization, and dehydration and act as a major structural component of the
      extracellular matrix in biofilms. They contribute to biofilm-related resistance
      by acting as a diffusion barrier to positively charged antimicrobial agents
      including cationic antimicrobial peptides (CAPs). We previously created novel
      CAPs consisting of a nonamphipathic hydrophobic core flanked by Lys residues and
      containing a Trp residue in the hydrophobic segment as a fluorescent probe.
      Peptides of this type above a specific hydrophobicity threshold insert
      spontaneously into membranes and have antimicrobial activity against Gram
      positive and Gram-negative bacteria at micromolar concentrations. Here we show
      that alginate, a polymer of beta-d-mannuronate and alpha-l-guluronate secreted by
      the cystic fibrosis pathogen Pseudomonas aeruginosa, induces an alpha-helical
      conformation detected by circular dichroism spectroscopy and blue shifts in Trp
      fluorescence maxima in peptides above the hydrophobicity threshold, changes
      typically observed upon association of such peptides with nonpolar (membrane)
      environments. Parallel effects were observed in the archetypical CAPs magainin II
      amide and cecropin P1. Fluorescence resonance energy transfer studies indicated
      that alginate induces peptide-peptide association only in peptides above the
      hydrophobicity threshold, suggesting that the hydrophilic alginate polymer
      behaves as an "auxiliary membrane" for the bacteria, demonstrating a unique
      protective role for biofilm matrices against CAPs.

PMID- 15247258
TI  - Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by
      mevalonic acid depletion: synergy between protein prenylation and receptor
      glycosylation pathways.
AB  - The vasculoprotective effects of hydroxy-3-methylglutaryl (HMG)-CoA reductase
      inhibitors (statins) correlate with cholesterol lowering. HMG-CoA reductase
      inhibitors also disrupt cellular processes by the depletion of isoprenoids and
      dolichol. Insulin and insulin-like growth factor (IGF) signaling appear
      particularly prone to such disruption as intracellular receptor processing
      requires dolichol for correct N-glycosylation, whereas downstream signaling
      through Ras requires the appropriate prenylation (farnesol). We determined how
      HMG-CoA reductase inhibition affected the mitogenic effects of IGF-I and
      metabolic actions of insulin in 3T3-L1 cells and examined the respective roles of
      receptor glycosylation and Ras prenylation. IGF-I- and insulin-induced
      proliferation was significantly reduced by all statins tested, although
      cerivastatin (10 nm) had the greatest effect (p < 0.005). Although inhibitors of
      Ras prenylation induced similar results (10 microm FTI-277 89% +/- 7.4%, p <
      0.01), the effect of HMG-CoA reductase inhibition could only be partially
      reversed by farnesyl pyrophosphate refeeding. Treatment with statins resulted in
      decreased membrane expression of receptors and accumulation of proreceptors,
      suggesting disruption of glycosylation-dependent cleavage. Glycosylation
      inhibitors inhibited IGF-I-induced proliferation (tunicamycin p < 0.005,
      castanospermine p < 0.01, deoxymannojirimycin p < 0.01). High concentrations of
      statin were necessary to impair insulin-mediated glucose uptake (300 nm = 33% +/-
      12% p < 0.05), and this process was not effected by farnesyl transferase
      inhibition. Gycosylation inhibitors mimicked the effect of statin treatment
      (tunicamycin p < 0.001, castanospermine p < 0.05, deoxymannojirimycin p < 0.05),
      and there was insulin proreceptor accumulation. These data imply that HMG-CoA
      reductase inhibitors disrupt IGF-I signaling by combined effects on Ras
      prenylation and IGF receptor glycosylation, whereas insulin signaling is only
      affected by disrupted receptor glycosylation.

PMID- 15247259
TI  - Binding modes of the initiator and inhibitor forms of the replication protein pi
      to the gamma ori iteron of plasmid R6K.
AB  - Discerning the interactions between initiator protein and the origin of
      replication should provide insights into the mechanism of DNA replication
      initiation. In the gamma origin of plasmid R6K, the Rep protein, pi, is
      distinctive in that it can bind the seven 22-bp iterons in two forms; pi monomers
      activate replication, whereas pi dimers act as inhibitors. In this work, we used
      wild type and variants of the pi protein with altered monomer/dimer ratios to
      study iteron/pi interactions. High resolution contact mapping was conducted using
      multiple techniques (missing base contact probing, methylation protection, base
      modification, and hydroxyl radical footprinting), and the electrophoretic
      separation of nucleoprotein complexes allowed us to discriminate between contact
      patterns produced by pi monomers and dimers. We also isolated iteron mutants that
      affected the binding of pi monomers (only) or both monomers and dimers. The
      mutational studies and footprinting analyses revealed that, when binding DNA, pi
      monomers interact with nucleotides spanning the entire length of the iteron. In
      contrast, pi dimers interact with only the left half of the iteron; however, the
      retained interactions are strikingly similar to those seen with monomers. These
      results support a model in which Rep protein dimerization disturbs one of two DNA
      binding domains important for monomer/iteron interaction; the dimer/iteron
      interaction utilizes only one DNA binding domain.

PMID- 15247260
TI  - Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance
      regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP
      regulated Cl(-) channel expressed in the apical plasma membrane in fluid
      transporting epithelia. Although CFTR is rapidly endocytosed from the apical
      membrane of polarized epithelial cells and efficiently recycled back to the
      plasma membrane, little is known about the molecular mechanisms regulating CFTR
      endocytosis and endocytic recycling. Myosin VI, an actin-dependent, minus-end
      directed mechanoenzyme, has been implicated in clathrin-mediated endocytosis in
      epithelial cells. The goal of this study was to determine whether myosin VI
      regulates CFTR endocytosis. Endogenous, apical membrane CFTR in polarized human
      airway epithelial cells (Calu-3) formed a complex with myosin VI, the myosin VI
      adaptor protein Disabled 2 (Dab2), and clathrin. The tail domain of myosin VI, a
      dominant-negative recombinant fragment, displaced endogenous myosin VI from
      interacting with Dab2 and CFTR and increased the expression of CFTR in the plasma
      membrane by reducing CFTR endocytosis. However, the myosin VI tail fragment had
      no effect on the recycling of endocytosed CFTR or on fluid-phase endocytosis.
      CFTR endocytosis was decreased by cytochalasin D, an actin-filament
      depolymerizing agent. Taken together, these data indicate that myosin VI and Dab2
      facilitate CFTR endocytosis by a mechanism that requires actin filaments.

PMID- 15247261
TI  - A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and
      degradation by binding to ubiquitin-specific protease USP7.
AB  - Herpes simplex virus type 1 immediate-early regulatory protein ICP0 stimulates
      lytic infection and reactivation from latency, processes that require the
      ubiquitin E3 ligase activity mediated by the RING finger domain in the N-terminal
      portion of the protein. ICP0 stimulates the production of polyubiquitin chains by
      the ubiquitin-conjugating enzymes UbcH5a and UbcH6 in vitro, and in infected and
      transfected cells it induces the proteasome-dependent degradation of a number of
      cellular proteins including PML, the major constituent protein of PML nuclear
      bodies. However, ICP0 binds strongly to the cellular ubiquitin-specific protease
      USP7, a member of a family of proteins that cleave polyubiquitin chains and/or
      ubiquitin precursors. The region of ICP0 that is required for its interaction
      with USP7 has been mapped, and mutations in this domain reduce the functionality
      of ICP0. These findings pose the question: why does ICP0 include domains that are
      associated with the potentially antagonistic functions of ubiquitin conjugation
      and deconjugation? Here we report that although neither protein affected the
      intrinsic activities of the other in vitro, USP7 protected ICP0 from
      autoubiquitination in vitro, and their interaction can greatly increase the
      stability of ICP0 in vivo. These results demonstrate that RING finger-mediated
      autoubiquitination of ICP0 is biologically relevant and can be regulated by
      interaction with USP7. This principle may extend to a number of cellular RING
      finger E3 ubiquitin ligase proteins that have analogous interactions with
      ubiquitin-specific cleavage enzymes.

PMID- 15247262
TI  - Human BACE forms dimers and colocalizes with APP.
AB  - Beta-site APP-cleaving enzyme (BACE) is a membrane-bound aspartyl protease with
      no strict primary preference for cleavage. The molecular mechanisms that link the
      gamma-secretase multicomponent amyloid precursor protein (APP) processing complex
      to biochemical properties of BACE generating the N terminus of the amyloid beta
      peptide have not, as yet, been identified. We found that in human brain tissue,
      BACE occurred as a dimer. The overall stability of the BACE homodimer was based
      on intermolecular interactions that were not affected by high salt, nonionic
      detergents or reducing conditions. BACE homodimers could only partially be
      separated even under strong denaturing conditions and revealed dramatic
      differences in the surface charge distribution compared with the monomer. In
      contrast, the soluble ectodomain of truncated BACE revealed a seemingly lower
      avidity to the prototypic aspartate protease inhibitor pepstatin and exclusively
      occurred in the monomeric form. Immunocytochemical studies colocalized APP and
      BACE in the plasma membrane of cells expressing endogenous levels of BACE and
      overexpressing APP. In cells that were cotransfected with APP and a putative
      active site D289A mutant of BACE, colocalization persisted. Remaining enzyme
      activity was found to be attributable to the mutant protease. Accordingly,
      inactivation of the carboxyl-terminal active site motif of BACE without an
      impairment of overall enzyme activity suggests that the enzyme may act as a
      dimer. Thus, homodimerization of BACE may help the enzyme to acquire specific
      mechanisms to associate with its substrates to exert catalytic activity.

PMID- 15247263
TI  - Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification
      regulating poly(ADP-ribose) polymerase-1-topoisomerase I interaction.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification that occurs
      immediately after exposure of cells to DNA damaging agents. In vivo, 90% of ADP
      ribose polymers are attached to the automodification domain of poly(ADP-ribose)
      polymerase-1 (PARP-1), the main enzyme catalyzing this modification reaction.
      This enzyme forms complexes with transcription initiation, DNA replication, and
      DNA repair factors. In most known cases, the interactions occur through the
      automodification domain. However, functional implications of the automodification
      reaction on these interactions have not yet been elucidated. In the present
      study, we created fluorescent protein-tagged PARP-1 to study this enzyme in live
      cells and focused on the interaction between PARP-1 and topoisomerase I (Topo I),
      one of the enzymes that interacts with PARP-1 in vitro. Here, we demonstrate that
      PARP-1 co-localizes with Topo I throughout the cell cycle. Results from
      bioluminescence resonance energy transfer assays suggest that the co-localization
      is because of a direct protein-protein interaction. In response to DNA damage,
      PARP-1 de-localization and a reduction in bioluminescence resonance energy
      transfer signal because of the automodification reaction are observed, suggesting
      that the automodification reaction results in the disruption of the interaction
      between PARP-1 and Topo I. Because Topo I activity has been reported to be
      promoted by PARP-1, we then investigated the effect of the disruption of this
      interaction on Topo I activity, and we found that this disruption results in the
      reduction of Topo I activity. These results suggest that a function for the
      automodification reaction is to regulate the interaction between PARP-1 and Topo
      I, and consequently, the Topo I activity, in response to DNA damage.

PMID- 15247265
TI  - Changes in the spin state and reactivity of cytochrome C induced by
      photochemically generated singlet oxygen and free radicals.
AB  - This work compares the effect of photogenerated singlet oxygen
      (O(2)((1)Delta(g))) (type II mechanism) and free radicals (type I mechanism) on
      cytochrome c structure and reactivity. Both reactive species were obtained by
      photoexcitation of methylene blue (MB(+)) in the monomer and dimer forms,
      respectively. The monomer form is predominant at low dye concentrations (up to 8
      microm) or in the presence of an excess of SDS micelles, while dimers are
      predominant at 0.7 mm SDS. Over a pH range in which cytochrome c is in the native
      form, O(2) ((1)Delta(g)) and free radicals induced a Soret band blue shift (from
      409 to 405 nm), predominantly. EPR measurements revealed that the blue shift of
      the Soret band was compatible with conversion of the heme iron from its native
      low spin state to a high spin state with axial symmetry (g approximately 6.0).
      Soret band bleaching, due to direct attack on the heme group, was only detected
      under conditions that favored free radical production (MB(+) dimer in SDS
      micelles) or in the presence of a less structured form of the protein (above pH
      9.3). Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry of the heme group and the polypeptide chain of cytochrome c with
      Soret band at 405 nm (cytc405) revealed no alterations in the mass of the cytc405
      heme group but oxidative modifications on methionine (Met(65) and Met(80)) and
      tyrosine (Tyr(74)) residues. Damage of cytc405 tyrosine residue impaired its
      reduction by diphenylacetaldehyde, but not by beta-mercaptoethanol, which was
      able to reduce cytc405, generating cytochrome c Fe(II) in the high spin state
      (spin 2).

PMID- 15247264
TI  - Disruption of cortical actin in skeletal muscle demonstrates an essential role of
      the cytoskeleton in glucose transporter 4 translocation in insulin-sensitive
      tissues.
AB  - Cell culture work suggests that signaling to polymerize cortical filamentous
      actin (F-actin) represents a required pathway for the optimal redistribution of
      the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent
      in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich
      syndrome protein (N-WASP) mediates the effect of insulin on the actin filament
      network. Here we tested whether similar cytoskeletal mechanics are essential for
      insulin-regulated glucose transport in isolated rat epitrochlearis skeletal
      muscle. Microscopic analysis revealed that cortical F-actin is markedly
      diminished in muscle exposed to latrunculin B. Depolymerization of cortical F
      actin with latrunculin B caused a time- and concentration-dependent decline in 2
      deoxyglucose transport. The loss of cortical F-actin and glucose transport was
      paralleled by a decline in insulin-stimulated GLUT4 translocation, as assessed by
      photolabeling of cell surface GLUT4 with Bio-LC-ATB-BMPA. Although latrunculin B
      impaired insulin-stimulated GLUT4 translocation and glucose transport, activation
      of phosphatidylinositol 3-kinase and Akt by insulin was not rendered ineffective.
      In contrast, the ability of insulin to elicit the cortical F-actin localization
      of N-WASP was abrogated. These data provide the first evidence that actin
      cytoskeletal mechanics are an essential feature of the glucose transport process
      in intact skeletal muscle. Furthermore, these findings support a distal actin
      based role for N-WASP in insulin action in vivo.

PMID- 15247266
TI  - Role of EHD1 and EHBP1 in perinuclear sorting and insulin-regulated GLUT4
      recycling in 3T3-L1 adipocytes.
AB  - Insulin stimulates glucose transport in muscle and adipose tissues by recruiting
      intracellular membrane vesicles containing the glucose transporter GLUT4 to the
      plasma membrane. The mechanisms involved in the biogenesis of these vesicles and
      their translocation to the cell surface are poorly understood. Here, we report
      that an Eps15 homology (EH) domain-containing protein, EHD1, controls the normal
      perinuclear localization of GLUT4-containing membranes and is required for
      insulin-stimulated recycling of these membranes in cultured adipocytes. EHD1 is a
      member of a family of four closely related proteins (EHD1, EHD2, EHD3, and EHD4),
      which also contain a P-loop near the N terminus and a central coiled-coil domain.
      Analysis of cultured adipocytes stained with anti-GLUT4, anti-EHD1, and anti-EHD2
      antibodies revealed that EHD1, but not EHD2, partially co-localizes with
      perinuclear GLUT4. Expression of a dominant-negative construct of EHD1 missing
      the EH domain (DeltaEH-EHD1) markedly enlarged endosomes, dispersed perinuclear
      GLUT4-containing membranes throughout the cytoplasm, and inhibited GLUT4
      translocation to the plasma membranes of 3T3-L1 adipocytes stimulated with
      insulin. Similarly, small interfering RNA-mediated depletion of endogenous EHD1
      protein also markedly dispersed perinuclear GLUT4 in cultured adipocytes.
      Moreover, EHD1 is shown to interact through its EH domain with the protein EHBP1,
      which is also required for insulin-stimulated GLUT4 movements and hexose
      transport. In contrast, disruption of EHD2 function was without effect on GLUT4
      localization or translocation to the plasma membrane. Taken together, these
      results show that EHD1 and EHBP1, but not EHD2, are required for perinuclear
      localization of GLUT4 and reveal that loss of EHBP1 disrupts insulin-regulated
      GLUT4 recycling in cultured adipocytes.

PMID- 15247267
TI  - Metalloproteinase-dependent transforming growth factor-alpha release mediates
      neurotensin-stimulated MAP kinase activation in human colonic epithelial cells.
AB  - Expression of the neuropeptide neurotensin (NT) and its high affinity receptor
      (NTR1) is increased during the course of Clostridium difficile toxin A-induced
      acute colitis, and NTR1 antagonism attenuates the severity of toxin A-induced
      inflammation. We recently demonstrated in non-transformed human colonic
      epithelial NCM460 cells that NT treatment caused activation of a Ras-mediated MAP
      kinase pathway that significantly contributes to NT-induced interleukin-8 (IL-8)
      secretion. Here we used NCM460 cells, which normally express low levels of NTR1,
      and NCM460 cells stably transfected with NTR1 to identify the upstream signaling
      molecules involved in NT-NTR1-mediated MAP kinase activation. We found that
      inhibition of the epidermal growth factor receptor (EGFR) by either an EGFR
      neutralizing antibody or by its specific inhibitor AG1478 (0.2 microm) blocked NT
      induced MAP kinase activation. Moreover, NT stimulated tyrosine phosphorylation
      of the EGFR, and pretreatment with a broad spectrum metalloproteinase inhibitor
      batimastat reduced NT-induced MAP kinase activation. Using neutralizing
      antibodies against the EGFR ligands EGF, heparin-binding-EGF, transforming growth
      factor-alpha (TGFalpha), or amphiregulin we have shown that only the anti
      TGFalpha antibody significantly decreases NT-induced phosphorylation of EGFR and
      MAP kinases. Furthermore, inhibition of the EGF receptor by AG1478 significantly
      reduced NT-induced IL-8 promoter activity and IL-8 secretion. This is the first
      report demonstrating that NT binding to NTR1 transactivates the EGFR and that
      this response is linked to NT-mediated proinflammatory signaling. Our findings
      indicate that matrix metalloproteinase-mediated release of TGFalpha and
      subsequent EGFR transactivation triggers a NT-mediated MAP kinase pathway that
      leads to IL-8 gene expression in human colonic epithelial cells.

PMID- 15247268
TI  - Plasmin-induced migration requires signaling through protease-activated receptor
      1 and integrin alpha(9)beta(1).
AB  - Plasmin is a major extracellular protease that elicits intracellular signals to
      mediate platelet aggregation, chemotaxis of peripheral blood monocytes, and
      release of arachidonate and leukotriene from several cell types in a G protein
      dependent manner. Angiostatin, a fragment of plasmin(ogen), is a ligand and an
      antagonist for integrin alpha(9)beta(1). Here we report that plasmin specifically
      interacts with alpha(9)beta(1) and that plasmin induces of cells expressing
      migration recombinant alpha(9)beta(1) (alpha(9)-Chinese hamster ovary (CHO)
      cells). Migration was dependent on an interaction of the kringle domains of
      plasmin with alpha(9)beta(1) as well as the catalytic activity of plasmin.
      Angiostatin, representing the kringle domains of plasmin, alone did not induce
      the migration of alpha(9)-CHO cells, but simultaneous activation of the G protein
      coupled protease-activated receptor (PAR)-1 with an agonist peptide induced the
      migration on angiostatin, whereas PAR-2 or PAR-4 agonist peptides were without
      effect. Furthermore, a small chemical inhibitor of PAR-1 (RWJ 58259) and a
      palmitoylated PAR-1-blocking peptide inhibited plasmin-induced migration of
      alpha(9)-CHO cells. These results suggest that plasmin induces migration by
      kringle-mediated binding to alpha(9)beta(1) and simultaneous proteolytic
      activation of PAR-1.

PMID- 15247269
TI  - Induction of polyamine oxidase 1 by Helicobacter pylori causes macrophage
      apoptosis by hydrogen peroxide release and mitochondrial membrane depolarization.
AB  - Helicobacter pylori infects the human stomach by escaping the host immune
      response. One mechanism of bacterial survival and mucosal damage is induction of
      macrophage apoptosis, which we have reported to be dependent on polyamine
      synthesis by arginase and ornithine decarboxylase. During metabolic back
      conversion, polyamines are oxidized and release H(2)O(2), which can cause
      apoptosis by mitochondrial membrane depolarization. We hypothesized that this
      mechanism is induced by H. pylori in macrophages. Polyamine oxidation can occur
      by acetylation of spermine or spermidine by spermidine/spermine N(1)
      acetyltransferase prior to back-conversion by acetylpolyamine oxidase, but
      recently direct conversion of spermine to spermidine by the human polyamine
      oxidase h1, also called spermine oxidase, has been demonstrated. H. pylori
      induced expression and activity of the mouse homologue of this enzyme (polyamine
      oxidase 1 (PAO1)) by 6 h in parallel with ornithine decarboxylase, consistent
      with the onset of apoptosis, while spermidine/spermine N(1)-acetyltransferase
      activity was delayed until 18 h when late stage apoptosis had already peaked.
      Inhibition of PAO1 by MDL 72527 or by PAO1 small interfering RNA significantly
      attenuated H. pylori-induced apoptosis. Inhibition of PAO1 also significantly
      reduced H(2)O(2) generation, mitochondrial membrane depolarization, cytochrome c
      release, and caspase-3 activation. Overexpression of PAO1 by transient
      transfection induced macrophage apoptosis. The importance of H(2)O(2) was
      confirmed by inhibition of apoptosis with catalase. These studies demonstrate a
      new mechanism for pathogen-induced oxidative stress in macrophages in which
      activation of PAO1 leads to H(2)O(2) release and apoptosis by a mitochondrial
      dependent cell death pathway, contributing to deficiencies in host defense in
      diseases such as H. pylori infection.

PMID- 15247270
TI  - Translational control of putative protooncogene Nm23-M2 by cytokines via
      phosphoinositide 3-kinase signaling.
AB  - The expansion and differentiation of hematopoietic progenitors is regulated by
      cytokine and growth factor signaling. To examine how signal transduction controls
      the gene expression program required for progenitor expansion, we screened ATLAS
      filters with polysome-associated mRNA derived from erythroid progenitors
      stimulated with erythropoietin and/or stem cell factor. The putative proto
      oncogene nucleoside diphosphate kinase B (ndpk-B or nm23-M2) was identified as an
      erythropoietin and stem cell factor target gene. Factor-induced expression of
      nm23-M2 was regulated specifically at the level of polysome association by a
      phosphoinositide 3-kinase-dependent mechanism. Identification of the
      transcription initiation site revealed that nm23-M2 mRNA starts with a terminal
      oligopyrimidine sequence, which is known to render mRNA translation dependent on
      mitogenic factors. Recently, the nm23-M2 locus was identified as a common
      leukemia retrovirus integration site, suggesting that it plays a role in leukemia
      development. The expression of Nm23 from a retroviral vector in the absence of
      its 5'-untranslated region caused constitutive polysome association of nm23-M2.
      Polysome-association and protein expression of endogenous nm23-M2 declined during
      differentiation of erythroid progenitors, suggesting a role for Nm23-M2 in
      progenitor expansion. Taken together, nm23-m2 exemplifies that cytokine-dependent
      control of translation initiation is an important mechanism of gene expression
      regulation.

PMID- 15247271
TI  - ORF36 protein kinase of Kaposi's sarcoma herpesvirus activates the c-Jun N
      terminal kinase signaling pathway.
AB  - alpha-, beta-, and gamma-Herpesviruses encode putative viral protein kinases. The
      herpes simplex virus UL13, varicella-zoster virus ORF47, and Epstein-Barr virus
      BGLF4 genes all show protein kinase domains in their protein sequences.
      Mutational analysis of these herpesviruses demonstrated that the viral kinase is
      important for optimal virus growth. Previous studies have shown that ORF36 of
      Kaposi's sarcoma herpesvirus (KSHV) has protein kinase activity and is
      autophosphorylated on serine. The gene for ORF36 is expressed during lytic growth
      of the virus and has been classified as a late gene. Inspection of the ORF36
      sequence indicated potential motifs that could be involved in activation of
      cellular transcription factors. To analyze the function of ORF36, the cDNA for
      this viral gene was tagged with the FLAG epitope and inserted into an expression
      vector for mammalian cells. Transfection experiments in 293T and SLK cells
      demonstrated that expression of ORF36 resulted in phosphorylation of the c-Jun N
      terminal kinase. Autophosphorylation of ORF36 is important for JNK activation
      because a mutation in the predicted catalytic domain of ORF36 blocked its ability
      to phosphorylate JNK. Western blot analysis, using phosphospecific antibodies,
      revealed that mitogen-activated kinases MKK4 and MKK7 were phosphorylated by
      ORF36 but not by the kinase-negative mutant. Binding experiments in transfected
      cells also demonstrated that both the wild type and kinase-negative mutant of
      ORF36 form a complex with JNK, MKK4, and MKK7. In addition, using a tetracycline
      inducible Rta BCBL-1 cell line (TREx BCBL1-Rta), JNK was phosphorylated during
      lytic replication, and inhibition of JNK activation blocked late viral gene
      expression but not early viral gene expression. In summary, these studies
      demonstrate that KSHV ORF36 activates the JNK pathway; thus this cell signaling
      pathway may function in the KSHV life cycle by regulating viral and/or cellular
      transcription.

PMID- 15247272
TI  - Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint.
AB  - Mutations in the Drg1/RTP/Rit42 gene are commonly identified in hereditary
      neuropathies of the motor and sensory systems. This gene was also identified as a
      p53 target gene and a differentiation-related, putative metastatic suppressor
      gene in human colon and prostate cancer. In this study, we show that the Rit42
      protein is a microtubule-associated protein that localizes to the centrosomes and
      participates in the spindle checkpoint in a p53-dependent manner. When
      ectopically expressed and exposed to spindle inhibitors, Rit42 inhibited
      polyploidy in several p53-deficient tumor cell lines and increased the population
      of cells in mitotic arrest. Blocking endogenous Rit42 expression by small
      interfering RNA in normal human mammary epithelial cells resulted in the
      disappearance of astral microtubules, and dividing spindle fiber formation was
      rarely detected. Moreover, these cells underwent microtubule inhibitor-induced
      reduplication, leading to a polyploidy state. Our findings imply that Rit42 plays
      a role in the regulation of microtubule dynamics and the maintenance of euploidy.

PMID- 15247273
TI  - Lipoteichoic acid and toll-like receptor 2 internalization and targeting to the
      Golgi are lipid raft-dependent.
AB  - Lipoteichoic acid (LTA), a key cell wall component of Gram-positive bacteria,
      seems to function as an immune activator with characteristics very similar to
      lipopolysaccharide from Gram-negative bacteria. It has been shown that LTA binds
      CD14 and triggers activation via Toll-like receptor 2, but whether the activation
      occurs at the cell surface or internalization is required to trigger signaling
      has yet to be demonstrated. In this work we have investigated LTA binding and
      internalization and found that LTA and its receptor molecules accumulate in lipid
      rafts and are subsequently targeted rapidly to the Golgi apparatus. This
      internalization seems to be lipid raft-dependent because raft-disrupting drugs
      inhibited LTA/Toll-like receptor 2 colocalization in the Golgi. Similarly to
      lipopolysaccharide, LTA activation occurs at the cell surface, and the observed
      trafficking is independent of signaling.

PMID- 15247274
TI  - Cloning and characterization of cytokeratins 8 and 19 in adult rat striated
      muscle. Interaction with the dystrophin glycoprotein complex.
AB  - We used degenerate primers for the amino- and carboxyl-terminal ends of the rod
      domains of intermediate filament proteins in reverse transcriptase-PCR
      experiments to identify and clone cytokeratins 8 and 19 (K8 and K19) from cardiac
      muscle of the adult rat. Northern blots showed that K8 has a 2.2-kb transcript
      and K19 has a 1.9-kb transcript in both adult cardiac and skeletal muscles.
      Immunolocalization of the cytokeratins in adult cardiac muscle with isoform
      specific antibodies for K8 and K19 showed labeling at Z-lines within the muscle
      fibers and at Z-line and M-line domains at costameres at the sarcolemmal
      membrane. Dystrophin and K19 could be co-immunoprecipitated and co-purified from
      extracts of cardiac muscle, suggesting a link between the cytokeratins and the
      dystrophin-based cytoskeleton at the sarcolemma. Furthermore, transfection
      experiments indicate that K8 and K19 may associate with dystrophin through a
      specific interaction with its actin-binding domain. Consistent with this
      observation, the cytokeratins are disrupted at the sarcolemmal membrane of
      skeletal muscle of the mdx mouse that lacks dystrophin. Together these results
      indicate that at least two cytokeratins are expressed in adult striated muscle,
      where they may contribute to the organization of both the myoplasm and
      sarcolemma.

PMID- 15247275
TI  - Nuclear and nucleolar localization of 18-kDa fibroblast growth factor-2 is
      controlled by C-terminal signals.
AB  - Members of high (22-, 22.5-, 24-, and 34-kDa) and low (18-kDa) molecular mass
      forms of fibroblast growth factor-2 (FGF-2) regulate cell proliferation,
      differentiation, and migration. FGF-2s have been previously shown to accumulate
      in the nucleus and nucleolus. Although high molecular weight forms of FGF-2
      contain at least one nuclear localization signal (NLS) in their N-terminal
      extension, the 18-kDa FGF-2 does not contain a standard NLS. To determine signals
      controlling the nuclear and subnuclear localization of the 18-kDa FGF-2, its full
      length cDNA was fused to that of green fluorescent protein (GFP). The fusion
      protein was primarily localized to the nucleus of COS-7 and HeLa cells and
      accumulated in the nucleolus. The subcellular distribution was confirmed using
      wild type FGF-2 and FGF-2 tagged with a FLAG epitope. A 17-amino acid sequence
      containing two groups of basic amino acid residues separated by eight amino acid
      residues directed GFP and a GFP dimer into the nucleus. We systematically mutated
      the basic amino acid residues in this nonclassical NLS and determined the effect
      on nuclear and nucleolar accumulation of 18-kDa FGF-2. Lys(119) and Arg(129) are
      the key amino acid residues in both nuclear and nucleolar localization, whereas
      Lys(128) regulates only nucleolar localization of 18-kDa FGF-2. Together, these
      results demonstrate that the 18-kDa FGF-2 harbors a C-terminal nonclassical
      bipartite NLS, a portion of which also regulates its nucleolar localization.

PMID- 15247276
TI  - Protein phosphatase 2A, a negative regulator of the ERK signaling pathway, is
      activated by tyrosine phosphorylation of putative HLA class II-associated protein
      I (PHAPI)/pp32 in response to the antiproliferative lectin, jacalin.
AB  - Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine
      phosphatases that is involved in the control of many cellular functions including
      those mediated by extracellular signal-regulated kinase (ERK) signaling. While
      investigating the reversible antiproliferative effect of the dietary lectin,
      jacalin, which binds the Thomsen-Friedenreich antigen (galactose beta1-3 N
      acetylgalactosamine alpha-), we have found that this lectin (30 microg/ml)
      induces rapid, transient, tyrosine phosphorylation of putative human HLA-DR
      associated protein I (PHAPI, also known as the tumor suppressor pp32) in HT29
      human colon cancer cells. This is accompanied by the release of PP2A from
      association with PHAPI, allowing increased phosphatase activity of PP2A (by 42 +/
      10% at 10 min) and consequent complete dephosphorylation of the ERK kinase,
      MEK1/2, by 10 min and of ERK1/2 by 60 min. PHAPI knockdown by RNA interference
      abolished the effects of jacalin on PP2A activation and MEK inhibition. Thus
      phosphorylation of PHAPI/pp32 is a critical regulatory step in PP2A activation
      and ERK signaling.

PMID- 15247277
TI  - Involvement of Smad signaling in sphingosine 1-phosphate-mediated biological
      responses of keratinocytes.
AB  - The lysophospholipid sphingosine 1-phosphate and the cytokine-transforming growth
      factor beta are both released from degranulating platelets at wound sites,
      suggesting a broad spectrum of effects involved in wound healing. Interestingly,
      both of these molecules have been previously shown to induce chemotaxis but to
      strongly inhibit the growth of keratinocytes, while stimulating the proliferation
      of fibroblasts. In contrast to sphingosine 1-phosphate, the signaling cascade of
      the growth factor has been extensively examined. Specifically, Smad3 has been
      shown to be an essential mediator of transforming growth factor beta-dependent
      chemotaxis of keratinocytes and mediates, in part, its growth-inhibitory effect.
      Here we show that sphingosine 1-phosphate, independently of transforming growth
      factor beta secretion, induces a rapid phosphorylation of Smad3 on its C-terminal
      serine motif and induces its partnering with Smad4 and the translocation of the
      complex into the nucleus. Moreover, sphingosine 1-phosphate fails to induce
      chemotaxis or inhibit the growth of Smad3-deficient keratinocytes, suggesting
      that Smad3 plays an unexpected functional role as a new target in sphingosine 1
      phosphate signaling. Both sphingosine 1-phosphate receptors and the transforming
      growth factor beta-type I receptor serine/threonine kinase are essential for
      activation of Smad3 by this lysophospholipid and the dependent biological
      responses, indicating a novel cross-talk between serine/threonine kinase
      receptors and G-protein coupled receptors.

PMID- 15247278
TI  - Differential roles of the insulin and insulin-like growth factor-I (IGF-I)
      receptors in response to insulin and IGF-I.
AB  - Insulin and insulin-like growth factor-I (IGF-I) receptors are highly homologous
      tyrosine kinase receptors that share many common steps in their signaling
      pathways and have ligands that can bind to either receptor with differing
      affinities. To define precisely the signaling specific to the insulin receptor
      (IR) or the IGF-I receptor, we have generated brown preadipocyte cell lines that
      lack either receptor (insulin receptor knockout (IRKO) or insulin-like growth
      factor receptor knockout (IGFRKO)). Control preadipocytes expressed fewer insulin
      receptors than IGF-I receptors (20,000 versus 60,000), but during
      differentiation, insulin receptor levels increased so that mature adipocytes
      expressed slightly more insulin receptors than IGF-I receptors (120,000 versus
      100,000). In these cells, insulin stimulated IR homodimer phosphorylation,
      whereas IGF-I activated both IGF-I receptor homodimers and hybrid receptors.
      Insulin-stimulated IRS-1 phosphorylation was significantly impaired in IRKO cells
      but was surprisingly elevated in IGFRKO cells. IRS-2 phosphorylation was
      unchanged in either cell line upon insulin stimulation. IGF-I-dependent
      phosphorylation of IRS-1 and IRS-2 was ablated in IGFRKO cells but not in IRKO
      cells. In control cells, both insulin and IGF-I produced a dose-dependent
      increase in phosphorylated Akt and MAPK, although IGF-I elicited a stronger
      response at an equivalent dose. In IRKO cells, the insulin-dependent increase in
      phospho-Akt was completely abolished at the lowest dose and reached only 20% of
      the control stimulation at 10 nm. Most interestingly, the response to IGF-I was
      also impaired at low doses, suggesting that IR is required for both insulin- and
      IGF-I-dependent phosphorylation of Akt. Most surprisingly, insulin- or IGF-I
      dependent phosphorylation of MAPK was unaltered in either receptor-deficient cell
      line. Taken together, these results indicate that the insulin and IGF-I receptors
      contribute distinct signals to common downstream components in response to both
      insulin and IGF-I.

PMID- 15247279
TI  - Identification of metastasis-related genes in a mouse model using a library of
      randomized ribozymes.
AB  - Libraries of randomized ribozymes have considerable potential as tools for the
      identification of functional genes critically involved in a biological phenotype
      of interest in vitro. We have used a ribozyme library in an in vivo mouse model
      to identify genes related to metastasis. We injected weakly metastatic melanoma
      cells that had been treated with the library intravenously into mice. We then
      isolated ribozymes that accelerated metastasis from pulmonary tumors that had
      developed from metastasizing cells. As candidates for metastasis-related genes
      that were targets of the isolated ribozymes, we identified five unknown and three
      known genes: stromal interaction molecule 1 (STIM1), polymerase gamma2 accessory
      subunit (Polg2), and cytochrome P450, family 2, subfamily d, polypeptide 22
      (Cyp2d22). Repression of four of these by small interfering RNAs indeed resulted
      in the accelerated mobility of cells in in vitro scratch-wound assay. The further
      characterization of these candidate genes would provide clues to the complex
      mechanism(s) of metastasis.

PMID- 15247280
TI  - Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and
      ubiquitinates p53.
AB  - The human topoisomerase I- and p53-binding protein topors contains a highly
      conserved, N-terminal C3HC4-type RING domain that is homologous to the RING
      domains of known E3 ubiquitin ligases. We demonstrate that topors functions in
      vitro as a RING-dependent E3 ubiquitin ligase with the E2 enzymes UbcH5a, UbcH5c,
      and UbcH6 but not with UbcH7, CDC34, or UbcH2b. Additional studies indicate that
      a conserved tryptophan within the topors RING domain is required for
      ubiquitination activity. Furthermore, both in vitro and cellular studies
      implicate p53 as a ubiquitination substrate for topors. Similar to MDM2,
      overexpression of topors results in a proteasome-dependent decrease in p53
      protein expression in a human osteosarcoma cell line. These results are similar
      to the recent finding that a Drosophila topors orthologue ubiquitinates the Hairy
      transcriptional repressor and suggest that topors functions as a ubiquitin ligase
      for multiple transcription factors.

PMID- 15247281
TI  - Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to
      mediate NF-kappaB activation by toll-like receptor (TLR)-2 and TLR4.
AB  - The Toll-interleukin-1 receptor domain-containing adapter Mal (MyD88 adapter-like
      protein) is involved in Toll-like receptor (TLR)-2 and TLR4 signal transduction.
      However, no studies have yet identified a function for Mal distinct from the
      related adapter MyD88. In this study, we have identified a putative TRAF6
      interaction site in Mal but not in MyD88 and we demonstrate that Mal can be co
      immunoprecipitated with TRAF6. Overexpression of MalE190A, which contains a
      mutation within the TRAF6-binding motif, failed to induce the expression of an NF
      kappaB-dependent reporter gene, p65-mediated transactivation of gene expression,
      or activation of Jun N-terminal kinase or p42/p44 MAP kinase, which are induced
      with wild type Mal. MalE190A inhibited TLR2- and TLR4-mediated activation of NF
      kappaB. These results identify a specific role for Mal in TLR-mediated signaling
      in regulating NF-kappaB-dependent gene transcription via its interaction with
      TRAF6.

PMID- 15247282
TI  - Proteasome-dependent degradation of cyclin D1 in 1-methyl-4-phenylpyridinium ion
      (MPP+)-induced cell cycle arrest.
AB  - 1-Methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine, induces cell death and inhibition of cell
      proliferation in various cells. However, the mechanism whereby MPP(+) inhibits
      cell proliferation is still unclear. In this study, we found that MPP(+)
      suppressed the proliferation with accumulation in G(1) phase without inducing
      cell death in p53-deficient MG63 osteosarcoma cells. MPP(+) induced
      hypophosphorylation of retinoblastoma protein and rapidly down-regulated the
      protein but not mRNA levels of cyclin D1 in MG63 cells. The down-regulation of
      cyclin D1 protein was suppressed by a proteasome inhibitor, MG132. The cyclin D1
      down-regulation by MPP(+) was also observed in p53-positive PC12, HeLa S3, and
      HeLa rho(0) cells, which are a subclone of HeLa S3 lacking mitochondrial DNA.
      Moreover, MPP(+) dephosphorylated Akt in PC12 cells, which was rescued by the
      pretreatment with nerve growth factor. In addition, the pretreatment with nerve
      growth factor or lithium chloride, a glycogen synthase kinase-3beta inhibitor,
      suppressed the cyclin D1 down-regulation caused by MPP(+). Our results
      demonstrate that MPP(+) induces cell cycle arrest independently of its
      mitochondrial toxicity or the p53 status of the target cells, but rather through
      the proteasome- and phosphatidylinositol 3-Akt-glycogen synthase kinase-3beta
      dependent cyclin D1 degradation.

PMID- 15247283
TI  - Structure and function of the membrane anchor domain of hepatitis C virus
      nonstructural protein 5A.
AB  - Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a membrane-associated,
      essential component of the viral replication complex. Here, we report the three
      dimensional structure of the membrane anchor domain of NS5A as determined by NMR
      spectroscopy. An alpha-helix extending from amino acid residue 5 to 25 was
      observed in the presence of different membrane mimetic media. This helix
      exhibited a hydrophobic, Trprich side embedded in detergent micelles, while the
      polar, charged side was exposed to the solvent. Thus, the NS5A membrane anchor
      domain forms an in-plane amphipathic alpha-helix embedded in the cytosolic
      leaflet of the membrane bilayer. Interestingly, mutations affecting the
      positioning of fully conserved residues located at the cytosolic surface of the
      helix impaired HCV RNA replication without interfering with the membrane
      association of NS5A. In conclusion, the NS5A membrane anchor domain constitutes a
      unique platform that is likely involved in specific interactions essential for
      the assembly of the HCV replication complex and that may represent a novel target
      for antiviral intervention.

PMID- 15247284
TI  - Subsets of the major tyrosine phosphorylation sites in Crk-associated substrate
      (CAS) are sufficient to promote cell migration.
AB  - Crk-associated substrate (p130(CAS) or CAS) is a major integrin-associated Src
      substrate that undergoes tyrosine phosphorylation at multiple YXXP motifs in its
      substrate domain (SD) to create docking sites for SH2-containing signaling
      effectors. Notably, recruitment of Crk adaptor proteins to the CAS SD sites is
      implicated in promoting cell migration. However, it is unclear which or how many
      of the 15 CAS SD YXXP tyrosines are critically involved. To gain a better
      understanding of CAS SD function, we assessed the signaling capacity of
      individual YXXP motifs. Using site-directed mutagenesis combined with tryptic
      phosphopeptide mapping, we determined that the ten tyrosines in YXXP motifs 6-15
      are the major sites of CAS SD phosphorylation by Src. Phosphopeptide binding
      assays showed that all of these sites are capable of binding the Crk SH2 domain.
      To evaluate the requirement for CAS YXXP sites in stimulating cell migration, a
      series of phenylalanine substitution variants were expressed in CAS -/- mouse
      embryo fibroblasts. CAS expression enhanced the rate of cell migration into a
      monolayer wound in a manner dependent on the major sites of Src phosphorylation.
      Effective wound healing was achieved by CAS variants containing as few as four of
      the major sites, indicating sufficiency of partial SD signaling function in this
      cell migration response.

PMID- 15247285
TI  - Nuclear factor-inducing kinase plays a crucial role in osteopontin-induced
      MAPK/IkappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix
      metalloproteinase-9 activation.
AB  - We have recently demonstrated that osteopontin (OPN) induces nuclear factor
      kappaB (NFkappaB)-mediated promatrix metalloproteinase-2 activation through
      IkappaBalpha/IkappaBalpha kinase (IKK) signaling pathways. However, the molecular
      mechanism(s) by which OPN regulates promatrix metalloproteinase-9 (pro-MMP-9)
      activation, MMP-9-dependent cell motility, and tumor growth and the involvement
      of upstream kinases in regulation of these processes in murine melanoma cells are
      not well defined. Here we report that OPN induced alpha(v)beta(3) integrin
      mediated phosphorylation and activation of nuclear factor-inducing kinase (NIK)
      and enhanced the interaction between phosphorylated NIK and IKKalpha/beta in
      B16F10 cells. Moreover, NIK was involved in OPN-induced phosphorylations of MEK-1
      and ERK1/2 in these cells. OPN induced NIK-dependent NFkappaB activation through
      ERK/IKKalpha/beta-mediated pathways. Furthermore OPN enhanced NIK-regulated
      urokinase-type plasminogen activator (uPA) secretion, uPA-dependent pro-MMP-9
      activation, cell motility, and tumor growth. Wild type NIK, IKKalpha/beta, and
      ERK1/2 enhanced and kinase-negative NIK (mut NIK), dominant negative
      IKKalpha/beta (dn IKKalpha/beta), and dn ERK1/2 suppressed the OPN-induced
      NFkappaB activation, uPA secretion, pro-MMP-9 activation, cell motility, and
      chemoinvasion. Pretreatment of cells with anti-MMP-2 antibody along with anti-MMP
      9 antibody drastically inhibited the OPN-induced cell migration and
      chemoinvasion, whereas cells pretreated with anti-MMP-2 antibody had no effect on
      OPN-induced pro-MMP-9 activation suggesting that OPN induces pro-MMP-2 and pro
      MMP-9 activations through two distinct pathways. The level of active MMP-9 in the
      OPN-induced tumor was higher compared with control. To our knowledge, this is the
      first report that NIK plays a crucial role in OPN-induced NFkappaB activation,
      uPA secretion, and pro-MMP-9 activation through MAPK/IKKalpha/beta-mediated
      pathways, and all of these ultimately control the cell motility, invasiveness,
      and tumor growth.

PMID- 15247286
TI  - Structure-specific DNA-induced conformational changes in Taq polymerase revealed
      by small angle neutron scattering.
AB  - The DNA polymerase I from Thermus aquaticus (Taq polymerase) performs lagging
      strand DNA synthesis and DNA repair. Taq polymerase contains a polymerase domain
      for synthesizing a new DNA strand and a 5'-nuclease domain for cleaving RNA
      primers or damaged DNA strands. The extended crystal structure of Taq polymerase
      poses a puzzle on how this enzyme coordinates its polymerase and the nuclease
      activities to generate only a nick. Using contrast variation solution small angle
      neutron scattering, we have examined the conformational changes that occur in Taq
      polymerase upon binding "overlap flap" DNA, a structure-specific DNA substrate
      that mimics the substrate in strand replacement reactions. In solution, apoTaq
      polymerase has an overall expanded equilibrium conformation similar to that in
      the crystal structure. Upon binding to the DNA substrate, both the polymerase and
      the nuclease domains adopt more compact overall conformations, but these changes
      are not enough to bring the two active sites close enough to generate a nick.
      Reconstruction of the three-dimensional molecular envelope from small angle
      neutron scattering data shows that in the DNA-bound form, the nuclease domain is
      lifted up relative to its position in the non-DNA-bound form so as to be in
      closer contact with the thumb and palm subdomains of the polymerase domain. The
      results suggest that a form of structure sensing is responsible for the
      coordination of the polymerase and nuclease activities in nick generation.
      However, interactions between the polymerase and the nuclease domains can assist
      in the transfer of the DNA substrate from one active site to the other.

PMID- 15247287
TI  - The novel Cdc42 guanine nucleotide exchange factor, zizimin1, dimerizes via the
      Cdc42-binding CZH2 domain.
AB  - Rho family small GTPases are critical regulators of multiple cellular processes
      and activities. Dbl homology domain-containing proteins are the classical guanine
      nucleotide exchange factors (GEFs) responsible for activation of Rho proteins.
      Recently another group of mammalian Rho-GEFs was discovered that includes CDM
      (Ced-5, DOCK180, Myoblast city) proteins that activate Rac and zizimin1 that
      activates Cdc42 via a nonconventional GEF module that we named the CZH2 domain.
      We report here that zizimin1 dimerizes via the CZH2 domain and that dimers are
      the only form detected. Dimerization was mapped to a approximately 200-amino acid
      region that overlaps but is distinct from the Cdc42-binding sequences. Rotary
      shadowing electron microscopy revealed zizimin1 to be a symmetric, V-shaped
      molecule. Experiments with DOCK180 and homology analysis suggest that
      dimerization may be a general feature of CZH proteins. Deletion and mutation
      analysis indicated existence of individual Cdc42-binding sites in the zizimin1
      monomers. Kinetic measurements demonstrated increased binding affinity of Cdc42
      to zizimin1 at higher Cdc42 concentration, suggesting positive cooperativity.
      These features are likely to be critical for Cdc42 activation.

PMID- 15247288
TI  - IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under
      the limited accessible free iron conditions.
AB  - Increasing evidence suggests that IscS, a cysteine desulfurase, provides sulfur
      for assembly of transient iron-sulfur clusters in IscU. IscU appears to act as a
      scaffold and eventually transfers the assembled clusters to target proteins.
      However, the iron donor for the iron-sulfur cluster assembly largely remains
      elusive. Here we find that Escherichia coli IscU fails to assemble iron-sulfur
      clusters when the accessible "free" iron in solution is limited by an iron
      chelator sodium citrate. Remarkably, IscA, an iron-sulfur cluster assembly
      protein with an iron association constant of 3.0 x 10(19) m(-1), is able to
      overcome the iron limitation due to sodium citrate and deliver iron for the IscS
      mediated iron-sulfur cluster assembly in IscU. Substitution of the invariant
      cysteine residues Cys-99 or Cys-101 in IscA with serine completely abolishes the
      iron binding activity of the protein. The IscA mutants that fail to bind iron are
      unable to mediate iron delivery for the iron-sulfur cluster assembly in IscU
      under the limited accessible "free" iron conditions. The results suggest that
      IscA is capable of recruiting intracellular iron and providing iron for the iron
      sulfur cluster assembly in IscU in cells in which the accessible "free" iron
      content is probably restricted.

PMID- 15247290
TI  - Diffuse pharmacophoric domains of vasoactive intestinal peptide (VIP) and further
      insights into the interaction of VIP with the N-terminal ectodomain of human
      VPAC1 receptor by photoaffinity labeling with [Bpa6]-VIP.
AB  - The widespread 28-amino acid neuropeptide vasoactive intestinal peptide (VIP)
      exerts its many biological effects through interaction with serpentine class II G
      protein-coupled receptors named VPAC receptors. We previously provided evidence
      for a physical contact between the side chain at position 22 of VIP and the N
      terminal ectodomain of the hVPAC1 receptor (Tan, Y. V., Couvineau, A., Van
      Rampelbergh, J., and Laburthe, M. (2003) J. Biol. Chem. 278, 36531-36536). We
      explored here the contact site between hVPAC1 receptor and the side chain at
      position 6 of VIP by photoaffinity labeling. The photoreactive para-benzoyl-l-Phe
      (Bpa) was substituted for Phe(6) in VIP resulting in [Bpa(6)]-VIP, which was
      shown to be a hVPAC1 receptor agonist in Chinese hamster ovary cells stably
      expressing the recombinant receptor. After obtaining the covalent (125)I-[Bpa(6)
      VIP].hVPAC1 receptor complex, it was sequentially cleaved by cyanogen bromide,
      peptide N-glycosidase F, endopeptidase Glu-C, and trypsin, and the cleavage
      products were analyzed by electrophoresis. The data demonstrated that (125)I
      [Bpa(6)-VIP] were covalently attached to the short 104-108 fragment within the N
      terminal ectodomain of the receptor. The data were confirmed by creation of a
      receptor mutant with new CNBr cleavage site. In a three-dimensional model of the
      receptor N-terminal ectodomain, this fragment was located on one edge of the
      putative VIP-binding groove and was adjacent to the fragment covalently attached
      to the side chain at position 22 of VIP. Altogether these data showed that the
      central part of VIP, at least between Phe(6) and Tyr(22), interacts with the N
      terminal ectodomain of the hVPAC1 receptor.

PMID- 15247289
TI  - The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2
      as interacting ligands.
AB  - The C terminus (ct) of protein kinase C-alpha (PKCalpha) has a type I PDZ binding
      motif, whereas GluR2 has a type II PDZ binding motif. Both motifs are recognized
      by the PDZ domain of protein interacting with protein kinase C (PICK1), and PICK1
      PKCalpha-controlled phosphorylation regulates the synaptic expression and
      function of GluR2. Here, we show that a specific mutation within the carboxylate
      binding loop of the PDZ domain of PICK1 (K27E; PICK1-KE) results in a loss of
      interaction with GluR2 but not with PKCalpha. In GST pull-down studies, PICK1-WT
      (wild type) but not PICK1-KE was retained by GST-ct-GluR2. Furthermore, PICK1-WT
      co-immunoprecipitated both PKCalpha and GluR2, whereas PICK1-KE only co
      immunoprecipitated PKCalpha. In heterologous cells, PICK1-WT, but not PICK1-KE,
      clustered GluR2 and also clustered GluR1 in a GluR2-dependent manner. However,
      neither PICK1-WT nor PICK1-KE altered the distribution of PKCalpha, even after
      phorbol ester-induced redistribution of PKCalpha to the membrane. Finally, PICK1
      KE showed no mislocalization when compared with PICK1-WT in neurons. Taken
      together, it appears that the PDZ domain of PICK1 is less sensitive to mutations
      for PKCalpha when compared with GluR2 binding. These results suggest that the PDZ
      domain of PICK1 has distinct PKCalpha and GluR2 binding subsite(s).

PMID- 15247291
TI  - Presenilins and gamma-secretase inhibitors affect intracellular trafficking and
      cell surface localization of the gamma-secretase complex components.
AB  - The intramembranous cleavage of Alzheimer beta-amyloid precursor protein and the
      signaling receptor Notch is mediated by the presenilin (PS, PS1/PS2)-gamma
      secretase complex, the components of which also include nicastrin, APH-1, and PEN
      2. In addition to its essential role in gamma-secretase activity, we and others
      have reported that PS1 plays a role in intracellular trafficking of select
      membrane proteins including nicastrin. Here we examined the fate of PEN-2 in the
      absence of PS expression or gamma-secretase activity. We found that PEN-2 is
      retained in the endoplasmic reticulum and has a much shorter half-life in PS
      deficient cells than in wild type cells, suggesting that PSs are required for
      maintaining the stability and proper subcellular trafficking of PEN-2. However,
      the function of PS in PEN-2 trafficking is distinct from its contribution to
      gamma-secretase activity because inhibition of gamma-secretase activity by gamma
      secretase inhibitors did not affect the PEN-2 level or its egress from the
      endoplasmic reticulum. Instead, membrane-permeable gamma-secretase inhibitors,
      but not a membrane-impermeable derivative, markedly increased the cell surface
      levels of PS1 and PEN-2 without affecting that of nicastrin. In support of its
      role in PEN-2 trafficking, PS1 was also required for the gamma-secretase
      inhibitor-induced plasma membrane accumulation of PEN-2. We further showed that
      gamma-secretase inhibitors specifically accelerated the Golgi to the cell surface
      transport of PS1 and PEN-2. Taken together, we demonstrate an essential role for
      PSs in intracellular trafficking of the gamma-secretase components, and that
      selective gamma-secretase inhibitors differentially affect the trafficking of the
      gamma-secretase components, which may contribute to an inactivation of gamma
      secretase.

PMID- 15247292
TI  - Importance of Gly-13 for the coenzyme binding of human UDP-glucose dehydrogenase.
AB  - UDP-glucose dehydrogenase (UGDH) is the unique pathway enzyme furnishing in
      vertebrates UDP-glucuronate for numerous transferases. In this report, we have
      identified an NAD(+)-binding site within human UGDH by photoaffinity labeling
      with a specific probe, [(32)P]nicotinamide 2-azidoadenosine dinucleotide (2N(3)
      NAD(+)), and cassette mutagenesis. For this work, we have chemically synthesized
      a 1509-base pair gene encoding human UGDH and expressed it in Escherichia coli as
      a soluble protein. Photolabel-containing peptides were generated by photolysis
      followed by tryptic digestion and isolated using the phosphopeptide isolation
      kit. Photolabeling of these peptides was effectively prevented by the presence of
      NAD(+) during photolysis, demonstrating a selectivity of the photoprobe for the
      NAD(+)-binding site. Amino acid sequencing and compositional analysis identified
      the NAD(+)-binding site of UGDH as the region containing the sequence
      ICCIGAXYVGGPT, corresponding to Ile-7 through Thr-19 of the amino acid sequence
      of human UGDH. The unidentified residue, X, can be designated as a photolabeled
      Gly-13 because the sequences including the glycine residue in question have a
      complete identity with those of other UGDH species known. The importance of Gly
      13 residue in the binding of NAD(+) was further examined with a G13E mutant by
      cassette mutagenesis. The mutagenesis at Gly-13 had no effects on the expression
      or stability of the mutant. Enzyme activity of the G13E point mutant was not
      measurable under normal assay conditions, suggesting an important role for the
      Gly-13 residue. No incorporation of [(32)P]2N(3)NAD(+) was observed for the G13E
      mutant. These results indicate that Gly-13 plays an important role for efficient
      binding of NAD(+) to human UGDH.

PMID- 15247294
TI  - Major histocompatibility class II transactivator (CIITA) mediates repression of
      collagen (COL1A2) transcription by interferon gamma (IFN-gamma).
AB  - Interferon gamma (IFN-gamma) plays an important role during inflammation by
      repressing collagen and activating major histocompatibility class II (MHC-II)
      expression. Activation of MHC-II by IFN-gamma requires regulatory factor for X
      box 5 (RFX5) complex as well as class II transactivator (CIITA). We have shown
      that the RFX family binds to the COL1A2 transcription start site, and the RFX5
      complex represses COL1A2 gene expression during IFN-gamma response. In this
      report, we demonstrate that CIITA is a key mediator of COL1A2 repression by IFN
      gamma. IFN-gamma up-regulates the expression of CIITA in a time-dependent manner
      in lung fibroblasts and promotes CIITA protein occupancy on COL1A2 transcription
      start site in vivo as judged by chromatin immunoprecipitation (ChIP) assays.
      There are coordinate decreases in the occupancy of RNA polymerase II on the
      collagen transcription start site with increasing CIITA occupancy during IFN
      gamma treatment. In addition, we are able to specifically knockdown the IFN-gamma
      stimulated expression of CIITA utilizing short hairpin interference RNA (shRNA)
      against CIITA. This leads to the alleviation of COL1A2 repression and MHC-II
      activation by IFN-gamma. RFX5 recruits CIITA to the collagen site as evidenced by
      DNA affinity chromatography. The presence of RFX5 complex proteins enhances the
      collagen repression by CIITA reaching levels occurring during IFN-gamma
      treatment. Co-expression of CIITA with deletion mutations and collagen promoter
      constructs demonstrates that CIITA represses collagen promoter mainly through its
      N-terminal region including the acidic domain and the proline/serine/threonine
      domain. Our data suggest that CIITA is a crucial member of a repressor complex
      responsible for mediating COL1A2 transcription repression by IFN-gamma.

PMID- 15247295
TI  - Detection of 2-O-sulfated iduronate and N-acetylglucosamine units in heparan
      sulfate by an antibody selected against acharan sulfate (IdoA2S-GlcNAc)n.
AB  - The snail glycosaminoglycan acharan sulfate (AS) is structurally related to
      heparan sulfates (HS) and has a repeating disaccharide structure of alpha-d-N
      acetylglucosaminyl-2-O-sulfo-alpha-l-iduronic acid (GlcNAc-IdoA2S) residues.
      Using the phage display technology, a unique antibody (MW3G3) was selected
      against AS with a V(H)3, DP 47, and a CDR3 amino acid sequence of QKKRPRF.
      Antibody MW3G3 did not react with desulfated, N-deacetylated or N-sulfated AS,
      indicating that reactivity depends on N-acetyl and 2-O-sulfate groups. Antibody
      MW3G3 also had a high preference for (modified) heparin oligosaccharides
      containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues. In
      tissues, antibody MW3G3 identified a HS oligosaccharide epitope containing N
      acetylated glucosamine and 2-O-sulfated iduronic acid residues as enzymatic N
      deacetylation of HS in situ prevented staining, and 2-O-sulfotransferase
      deficient Chinese hamster ovary cells were not reactive. An immunohistochemical
      survey using various rat organs revealed a distinct distribution of the MW3G3
      epitope, which was primarily present in the basal laminae of most (but not all)
      blood vessels and of some epithelia, including human skin. No staining was
      observed in the glycosaminoglycan-rich tumor matrix of metastatic melanoma. In
      conclusion, we have selected an antibody that identifies HS oligosaccharides
      containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues. This
      antibody may be instrumental in identifying structural alterations in HS in
      health and disease.

PMID- 15247293
TI  - Mechanistic analysis of the mitotic kinesin Eg5.
AB  - Eg5 is a slow, plus-end-directed microtubule-based motor of the BimC kinesin
      family that is essential for bipolar spindle formation during eukaryotic cell
      division. We have analyzed two human Eg5/KSP motors, Eg5-367 and Eg5-437, and
      both are monomeric based on results from sedimentation velocity and sedimentation
      equilibrium centrifugation as well as analytical gel filtration. The steady-state
      parameters were: for Eg5-367: k(cat) = 5.5 s(-1), K(1/2,Mt) = 0.7 microm, and
      K(m,ATP) = 25 microm; and for Eg5-437: k(cat) = 2.9 s(-1), K(1/2,Mt) = 4.5
      microm, and K(m,ATP) = 19 microm. 2'(3')-O-(N-Methylanthraniloyl)-ATP (mantATP)
      binding was rapid at 2-3 microm(-1)s(-1), followed immediately by ATP hydrolysis
      at 15 s(-1). ATP-dependent Mt.Eg5 dissociation was relatively slow and rate
      limiting at 8 s(-1) with mantADP release at 40 s(-1). Surprisingly, Eg5-367 binds
      microtubules more effectively (11 microm(-1)s(-1)) than Eg5-437 (0.7 microm(-1)s(
      1)), consistent with the steady-state K(1/2,Mt) and the mantADP release
      K(1/2,Mt). These results indicate that the ATPase pathway for monomeric Eg5 is
      more similar to conventional kinesin than the spindle motors Ncd and Kar3, where
      ADP product release is rate-limiting for steady-state turnover.

PMID- 15247296
TI  - Protein-DNA array-based identification of transcription factor activities
      regulated by interaction with the glucocorticoid receptor.
AB  - The glucocorticoid receptor (GR) regulates gene expression by binding specific
      sequence elements within the promoters of target genes or by cross-talk with
      other transcription factors (TFs). For some TFs, interaction with the GR results
      in alteration of DNA binding and transcriptional regulation. We used a protein
      DNA array, a system that facilitates simultaneous profiling of the activities of
      multiple transcription factors, to systematically examine the potential cross
      talk of GRalpha with 149 TFs. Using this array, we identified several TFs,
      including IRF, E47, and COUP-TF, whose DNA binding activities were modulated by
      GRalpha. We then confirmed these results with in vitro electrophoretic mobility
      shift assays and in vivo reporter assays. In this study, IRF and E47 were
      identified as participants in GRalpha cross-talk for the first time. This new
      finding expands our understanding of the functional role of GRalpha in the
      context of gene expression regulation.

PMID- 15247297
TI  - D1 dopamine receptor mediates dopamine-induced cytotoxicity via the ERK signal
      cascade.
AB  - Postsynaptic striatal neurodegeneration occurs through unknown mechanisms, but it
      is linked to high extracellular levels of synaptic dopamine. Dopamine-mediated
      cytotoxicity of striatal neurons occurs through two distinct pathways:
      autoxidation and the D1 dopamine receptor-linked signaling pathway. Here we
      investigated the mitogen-activated protein kinase (MAPK) signaling pathways
      activated upon the acute stimulation of D1 dopamine receptors. In SK-N-MC
      neuroblastoma cells, endogenously expressing D1 dopamine receptors, dopamine
      caused activation of phosphorylated (p-)ERK1/2 and of the stress-signaling
      kinases, p-JNK and p-p38 MAPK, in a time- and dose-dependent manner. Selective
      stimulation of D1 receptors with the agonist SKF R-38393 caused p-ERK1/2, but not
      p-JNK or p-p38 MAPK activation, in a manner sensitive to the receptor-selective
      antagonist SCH 23390, protein kinase A inhibition (KT5720), and MEK1/2 inhibition
      (U0126 or PD98059). Activation of ERK by D1 dopamine receptors resulted in
      oxidative stress and cytotoxicity. In cells transfected with a catalytically
      defective mutant of MEK1, the upstream ERK-specific kinase, both dopamine- and
      SKF R-38393-mediated cytotoxicity was markedly attenuated, confirming the
      participation of the ERK signaling pathway. Cell fractionation studies showed
      that only a small amount of p-ERK1/2 was translocated to the nucleus, with the
      majority retained in the cytoplasm. From coimmunoprecipitation studies, p-ERK was
      found to form stable heterotrimeric complexes with the D1 dopamine receptor and
      beta-arrestin2. In cells transfected with the dominant negative mutant of beta
      arrestin2, the formation of such complexes was substantially inhibited. These
      data provide novel mechanistic insights into the role of ERK in the cytotoxicity
      mediated upon activation of the D1 dopamine receptor.

PMID- 15247298
TI  - The Pho80-like cyclin of Aspergillus nidulans regulates development independently
      of its role in phosphate acquisition.
AB  - In Saccharomyces cerevisiae, phosphate acquisition enzymes are regulated by a
      cyclin-dependent kinase (Pho85), a cyclin (Pho80), the cyclin-dependent kinase
      inhibitor Pho81, and the helix-loop-helix transcription factor Pho4 (the PHO
      system). Previous studies in Aspergillus nidulans indicate that a Pho85-like
      kinase, PHOA, does not regulate the classic PHO system but regulates development
      in a phosphate-dependent manner. A Pho80-like cyclin has now been isolated
      through its interaction with PHOA. Surprisingly, unlike PHOA, An-PHO80 does play
      a negative role in the PHO system. Similarly, an ortholog of Pho4 previously
      identified genetically as palcA also regulates the PHO system. However, An-PHO81,
      a putative cyclin-dependent kinase inhibitor, does not regulate the PHO system.
      Therefore, there are significant differences between the classic PHO system
      conserved between S. cerevisiae and Neurospora crassa compared with that which
      has evolved in A. nidulans. Most interestingly, under low phosphate conditions,
      the An-PHO80 cyclin also promotes sexual development while having a negative
      effect on asexual development. These effects are independent of the role An-PHO80
      has in the classic PHO system. However, in high phosphate medium, An-PHO80
      affects development because of deregulation of the PHO system as loss of
      palcA(Pho4) function negates the developmental defects caused by lack of An
      pho80. Therefore, under low phosphate conditions the An-PHO80 cyclin regulates
      development independently of the PHO system, whereas in high phosphate it affects
      development through the PHO system. The data indicate that a single cyclin can
      control various aspects of growth and development in a multicellular organism.

PMID- 15247299
TI  - Type F scavenger receptor SREC-I interacts with advillin, a member of the
      gelsolin/villin family, and induces neurite-like outgrowth.
AB  - The scavenger receptor expressed by endothelial cells (SREC) was isolated from a
      human endothelial cell line and consists of two isoforms named SREC-I and -II.
      Both isoforms have no significant homology to other types of scavenger receptors.
      They contain 10 repeats of epidermal growth factor-like cysteine-rich motifs in
      the extracellular domains and have unusually long C-terminal cytoplasmic domains
      with Ser/Pro-rich regions. The extracellular domain of SREC-I binds modified low
      density lipoprotein and mediates a homophilic SREC-I/SREC-I or heterophilic SREC
      I/SREC-II trans-interaction. However, the significance of large Ser/Pro-rich
      cytoplasmic domains of SRECs is not clear. Here, we found that when SREC-I was
      overexpressed in murine fibroblastic L cells, neurite-like outgrowth was induced,
      indicating that the receptor can lead to changes in cell morphology. The SREC-I
      mediated morphological change required the cytoplasmic domain of the protein, and
      we identified advillin, a member of the gelsolin/villin family of actin
      regulatory proteins, as a protein binding to this domain. Reduction of advillin
      expression in L cells by RNAi led to the absence of the described SREC-I-induced
      morphological changes, indicating that advillin is a prerequisite for the change.
      Finally, we demonstrated that SREC-I and advillin were co-expressed and
      interacted with each other in dorsal root ganglion neurons during embryonic
      development and that overexpression of both SREC-I and advillin in cultured Neuro
      2a cells induced long process formation. These results suggest that the
      interaction of SREC-I and advillin are involved in the development of dorsal root
      ganglion neurons by inducing the described morphological changes.

PMID- 15247300
TI  - Mitochondrial bound hexokinase activity as a preventive antioxidant defense:
      steady-state ADP formation as a regulatory mechanism of membrane potential and
      reactive oxygen species generation in mitochondria.
AB  - Brain hexokinase is associated with the outer membrane of mitochondria, and its
      activity has been implicated in the regulation of ATP synthesis and apoptosis.
      Reactive oxygen species (ROS) are by-products of the electron transport chain in
      mitochondria. Here we show that the ADP produced by hexokinase activity in rat
      brain mitochondria (mt-hexokinase) controls both membrane potential (Deltapsi(m))
      and ROS generation. Exposing control mitochondria to glucose increased the rate
      of oxygen consumption and reduced the rate of hydrogen peroxide generation.
      Mitochondrial associated hexokinase activity also regulated Deltapsi(m), because
      glucose stabilized low Deltapsi(m) values in state 3. Interestingly, the addition
      of glucose 6-phosphate significantly reduced the time of state 3 persistence,
      leading to an increase in the Deltapsi(m) and in H(2)O(2) generation. The glucose
      analogue 2-deoxyglucose completely impaired H(2)O(2) formation in state 3-state 4
      transition. In sharp contrast, the mt-hexokinase-depleted mitochondria were, in
      all the above mentioned experiments, insensitive to glucose addition, indicating
      that the mt-hexokinase activity is pivotal in the homeostasis of the
      physiological functions of mitochondria. When mt-hexokinase-depleted mitochondria
      were incubated with exogenous yeast hexokinase, which is not able to bind to
      mitochondria, the rate of H(2)O(2) generation reached levels similar to those
      exhibited by control mitochondria only when an excess of 10-fold more enzyme
      activity was supplemented. Hyperglycemia induced in embryonic rat brain cortical
      neurons increased ROS production due to a rise in the intracellular glucose 6
      phosphate levels, which were decreased by the inclusion of 2-deoxyglucose, N
      acetyl cysteine, or carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Taken
      together, the results presented here indicate for the first time that mt
      hexokinase activity performed a key role as a preventive antioxidant against
      oxidative stress, reducing mitochondrial ROS generation through an ADP-recycling
      mechanism.

PMID- 15247301
TI  - Class II major histocompatibility complex transactivator (CIITA) inhibits matrix
      metalloproteinase-9 gene expression.
AB  - Matrix metalloproteinases (MMPs) are a family of structurally related proteins
      with the collective capability to degrade all components of the extracellular
      matrix. Although MMP-mediated degradation of the extracellular matrix occurs
      physiologically, numerous pathological conditions exhibit increased MMP levels
      and excessive matrix degradation. Previous work from our laboratory has shown
      that interferon-gamma inhibits MMP-9 expression in a manner dependent upon STAT
      1alpha. Here we extend our previous observations and show that the class II major
      histocompatibility complex transactivator (CIITA), a transcriptional target of
      STAT-1alpha, is also capable of inhibiting MMP-9 expression. By using stable cell
      lines that inducibly express CIITA or various mutant forms of CIITA, we show that
      CIITA requires the ability to bind the CREB-binding protein (CBP) to effectively
      inhibit MMP-9 expression. Furthermore, we show that CIITA-mediated inhibition of
      the MMP-9 gene does not rely on the transcriptional capability of CIITA. These
      findings support a model wherein CIITA inhibits MMP-9 expression by binding to
      and sequestering CBP, which reduces the levels of CBP at the MMP-9 promoter,
      inhibits levels of acetylated histone 3 at the MMP-9 promoter, and subsequently
      inhibits MMP-9 expression.

PMID- 15247302
TI  - A primate-dominant third glycosylation site of the beta2-adrenergic receptor
      routes receptors to degradation during agonist regulation.
AB  - beta(2)-adrenergic receptors (beta(2)AR) of all species are N-linked glycosylated
      at amino terminus residues approximately 6 and approximately 15. However, the
      human beta(2)AR has a potential third N-glycosylation site at ECL2 residue 187.
      To determine whether this residue is glycosylated and to ascertain function, all
      possible single/multiple Asn --> Gln mutations were made in the human beta(2) AR
      at positions 6, 15, and 187 and were expressed in Chinese hamster fibroblast
      cells. Substitution of Asn-187 alone or with Asn-6 or Asn-15 decreased the
      apparent molecular mass of the receptor on SDS-PAGE in a manner consistent with
      Asn-187 glycosylation. All receptors bound the agonist isoproterenol and
      functionally coupled to adenylyl cyclase. However, receptors without 187
      glycosylation failed to display long term agonist-promoted down-regulation. In
      contrast, loss of Asn-6/Asn-15 glycosylation did not alter down-regulation. Cell
      surface distribution and agonist-promoted internalization of receptors and
      recruitment of beta-arrestin 2 were unaffected by the loss of 187 glycosylation.
      Furthermore, acutely internalized wild-type and Gln-187 receptors were both
      localized by confocal microscopy to early endosomes. During prolonged agonist
      exposure, wild-type beta(2)AR co-localized with lysosomes, consistent with
      trafficking to a degradation compartment. However, Gln-187 beta(2)AR failed to co
      localize with lysosomes despite agonist treatments up to 18 h. Phylogenetic
      analysis revealed that this third glycosylation site is found in humans and other
      higher order primates but not in lower order primates such as the monkey. Nor is
      this third site found in rodents, which are frequently utilized as animal models.
      These data thus reveal a previously unrecognized beta(2)AR regulatory motif that
      appeared late in primate evolution and serves to direct internalized receptors to
      lysosomal degradation during long term agonist exposure.

PMID- 15247303
TI  - Nicotine-induced up-regulation and desensitization of alpha4beta2 neuronal
      nicotinic receptors depend on subunit ratio.
AB  - Desensitization induced by chronic nicotine exposure has been hypothesized to
      trigger the up-regulation of the alpha4beta2 neuronal nicotinic acetylcholine
      receptor (nAChR) in the central nervous system. We studied the effect of acute
      and chronic nicotine exposure on the desensitization and up-regulation of
      different alpha4beta2 subunit ratios (1alpha:4beta, 2alpha:3beta, and
      4alpha:1beta) expressed in Xenopus oocytes. The presence of alpha4 subunit in the
      oocyte plasmatic membrane increased linearly with the amount of alpha4 mRNA
      injected. nAChR function and expression were assessed during acute and after
      chronic nicotine exposure using a two-electrode voltage clamp and whole-mount
      immunofluorescence assay along with confocal imaging for the detection of the
      alpha4 subunit. The 2alpha4:3beta2 subunit ratio displayed the highest ACh
      sensitivity. Nicotine dose-response curves for the 1alpha4:4beta2 and
      2alpha4:3beta2 subunit ratios displayed a biphasic behavior at concentrations
      ranging from 0.1 to 300 microm. A biphasic curve for 4alpha4:1beta2 was obtained
      at nicotine concentrations higher than 300 microm. The 1alpha4:4beta2 subunit
      ratio exhibited the lowest ACh- and nicotine-induced macroscopic current, whereas
      4alpha4:1beta2 presented the largest currents at all agonist concentrations
      tested. Desensitization by acute nicotine exposure was more evident as the ratio
      of beta2:alpha4 subunits increased. All three alpha4beta2 subunit ratios
      displayed a reduced state of activation after chronic nicotine exposure. Chronic
      nicotine-induced up-regulation was obvious only for the 2alpha4: 3beta2 subunit
      ratio. Our data suggest that the subunit ratio of alpha4beta2 determines the
      functional state of activation, desensitization, and up-regulation of this
      neuronal nAChR. We propose that independent structural sites regulate alpha4beta2
      receptor activation and desensitization.

PMID- 15247304
TI  - Mechanism of nucleotide binding to actomyosin VI: evidence for allosteric head
      head communication.
AB  - We have examined the kinetics of nucleotide binding to actomyosin VI by
      monitoring the fluorescence of pyrene-labeled actin filaments. ATP binds single
      headed myosin VI following a two-step reaction mechanism with formation of a low
      affinity collision complex (1/K(1)' = 5.6 mm) followed by isomerization (k(+2)' =
      176 s-1) to a state with weak actin affinity. The rates and affinity for ADP
      binding were measured by kinetic competition with ATP. This approach allows a
      broader range of ADP concentrations to be examined than with fluorescent
      nucleotide analogs, permitting the identification and characterization of
      transiently populated intermediates in the pathway. ADP binding to actomyosin VI,
      as with ATP binding, occurs via a two-step mechanism. The association rate
      constant for ADP binding is approximately five times greater than for ATP binding
      because of a higher affinity in the collision complex (1/K(5b)' = 2.2 mm) and
      faster isomerization rate constant (k(+5a)' = 366 s(-1)). By equilibrium
      titration, both heads of a myosin VI dimer bind actin strongly in rigor and with
      bound ADP. In the presence of ATP, conditions that favor processive stepping,
      myosin VI does not dwell with both heads strongly bound to actin, indicating that
      the second head inhibits strong binding of the lead head to actin. With both
      heads bound strongly, ATP binding is accelerated 2.5-fold, and ADP binding is
      accelerated >10-fold without affecting the rate of ADP release. We conclude that
      the heads of myosin VI communicate allosterically and accelerate nucleotide
      binding, but not dissociation, when both are bound strongly to actin.

PMID- 15247305
TI  - The adaptor protein Bam32 regulates Rac1 activation and actin remodeling through
      a phosphorylation-dependent mechanism.
AB  - The B cell adaptor molecule of 32 kDa (Bam32) is an adaptor that links the B cell
      antigen receptor (BCR) to ERK and JNK activation and ultimately to mitogenesis.
      After BCR cross-linking, Bam32 is recruited to the plasma membrane and
      accumulates within F-actin-rich membrane ruffles. Bam32 contains one Src homology
      2 and one pleckstrin homology domain and is phosphorylated at a single site,
      tyrosine 139. To define the function of Bam32 in membrane-proximal signaling
      events, we established human B cell lines overexpressing wild-type or mutant
      Bam32 proteins. The basal level of F-actin increased in cells expressing wild
      type or myristoylated Bam32 but decreased in cells expressing either an Src
      homology-2 or Tyr-139 Bam32 mutant. Overexpression of wild-type Bam32 also
      affected BCR-induced actin remodeling, which was visualized as increases in F
      actin-rich membrane ruffles. In contrast, Bam32 mutants largely blocked the BCR
      induced increase in cellular F-actin. The positive and negative effects of Bam32
      variants on F-actin levels were closely mirrored by their effects on the
      activation of the GTPase Rac1, which is known to regulate actin remodeling in
      lymphocytes. Bam32-deficient DT40 B cells showed decreased Rac1 activation and a
      failure of Rac1 to co-localize with the BCR, whereas cells overexpressing Bam32
      had increased constitutive Rac1 activation. These results suggest that Bam32
      regulates the cytoskeleton through Rac1. Bam32 variants also affected downstream
      signaling to JNK in a manner similar to that of Rac1, suggesting that the effect
      of Bam32 on JNK activation may be at least partially mediated through Rac1. Our
      results demonstrate a novel phosphorylation-dependent function of Bam32 in
      regulating Rac1 activation and actin remodeling.

PMID- 15247306
TI  - Premeiotic clusters of mutation and the cost of natural selection.
AB  - Haldane stated that there is a cost of natural selection for new beneficial
      alleles to be substituted over time. Most of this cost, which leads to "genetic
      deaths," is in the early generations of the substitution process when the new
      allele is low in frequency. It depends on the initial frequency and dominance
      value, but not the selection coefficient, of the advantageous allele. There have
      been numerous suggestions on how to reduce the cost for preexisting genetic
      variation that goes from disadvantageous, or neutral, to advantageous with a
      change in the environment. However, the cost of natural selection for new alleles
      that arise by mutation is assumed to be high, based on the assumption that new
      mutant alleles arise in natural populations as single events [1/(2N) of the total
      alleles]. However, not all mutant alleles arise as single events. Premeiotic
      mutations occur frequently in individuals (germinal mosaics), giving rise to
      multiple copies of identical mutant alleles called a "cluster" (C) with an
      initial allele frequency of C/(2N) instead of 1/(2N). These clusters of new
      mutant alleles reduce the cost of natural selection in direct proportion to the
      relative size of the cluster. Hence new advantageous alleles that arise by
      mutation have the greatest chance of going to fixation if they occur in large
      clusters in small populations.

PMID- 15247307
TI  - Accumulation of transposable elements in the genome of Drosophila melanogaster is
      associated with a decrease in fitness.
AB  - Replicates of the two isogenic laboratory strains of Drosophila melanogaster, 2b
      and Harwich, contain different average transposable element (TE) copy numbers in
      the same genetic background. These lines were used to analyze the correlation
      between TE copy number and fitness. Assuming a weak deleterious effect of each TE
      insertion, a decrease in fitness is expected with an increase in genomic TE copy
      number. Higher rates of ectopic exchanges and, consequently, chromosomal
      rearrangements resulting in early embryonic death are also predicted from an
      increase in TE copy number. Therefore egg hatchability is expected to decrease as
      the genomic TE copy number increases. In 2b, where replicate lines have diverged
      up by 90 TE copies per haploid genome, a negative correlation between the number
      of TE insertions and both fitness and egg hatchability were found. Neither
      correlation was significant for the Harwich replicates, which have only diverged
      by 30 TE copies. The average deleterious effect of a TE insertion on fitness and
      its components was estimated as 0.004. Both homozygous and heterozygous TE
      insertions were shown to have deleterious effects on fitness and its components.

PMID- 15247308
TI  - Low genetic variability in the highly endangered mediterranean monk seal.
AB  - Genetic variability is an important component in the ability of populations to
      adapt in the face of environmental change. Here we report the first description
      of nuclear genetic variability in the only remaining sizable colony of the
      Mediterranean monk seal (Monachus monachus), located at Cap Blanc (Western
      Sahara, Mauritania), whose estimated size during the study period (1994-May 1997)
      was about 320 individuals. We tested 42 microsatellite loci isolated from five
      pinniped species in a sample of 52 pups. Three loci failed to give any product,
      and of the remaining 39, only 15 were polymorphic, with a maximum of 3 alleles
      detected. Three loci appeared to be X-linked. No departures from Hardy-Weinberg
      equilibrium were detected and no genetic structure was found between the two
      nursing caves currently occupied by the seals. Several analytical methods show
      that, as a consequence of a severe bottleneck, the population has suffered a
      decrease in genetic variability over the last few centuries.

PMID- 15247309
TI  - Genetic structure of Rhododendron ferrugineum at a wide range of spatial scales.
AB  - Rhododendron ferrugineum L. (Ericaceae) is a subalpine shrub found throughout the
      Pyrenees and Alps at elevations of 1600-2200 m. We examined relationships between
      genetic and geographic distance, using 115 dominant amplified fragment length
      polymorphism (AFLP) markers to assess genetic structure over a wide range of
      spatial scales. We sampled 17 sites with distances of 4 km to more than 1000 km
      between them. At these scales we detected no association between geographic
      distance and genetic distance between populations. This suggests that genetic
      drift and gene flow are not in equilibrium for these populations. This pattern
      could have resulted from recent and rapid postglacial colonization, from more
      recent human disturbance, or as a function of frequent and random "natural" long
      distance colonization. At two of our sites we used transects (two horizontal and
      two vertical with respect to slope at each site) to sample at distances ranging
      from 10 m to more than 5000 m. At this scale we observed a positive relationship
      between genetic and spatial distance along two vertical transects, one at each
      site. We hypothesize that isolation-by-distance at this smaller scale is a
      function of restricted gene flow via seed dispersal.

PMID- 15247310
TI  - Spatial and genetic structure within populations of wild American ginseng (Panax
      quinquefolius L., Araliaceae).
AB  - Spatial structure and fine-scale genetic structure were analyzed for the
      medicinal plant American ginseng (Panax quinquefolius L.) to more fully
      understand biological processes within wild populations. P. quinquefolius has
      been harvested for more than 250 years and is now considered threatened or rare
      throughout its range. Plants within four protected and four unprotected
      populations were significantly clumped based on Ripley's univariate analysis.
      Analysis with Ripley's bivariate test determined that juvenile plants were
      significantly clumped with adult plants at the shortest distance classes in all
      populations. Although plants were highly clumped, we found that significant fine
      scale genetic structure was restricted to the shortest distance classes based on
      estimates of coancestry (f(ij)). In most cases, estimates of f(ij) were more
      significant among juveniles than among adults, especially at the shortest
      distance classes. The spatial structure of ginseng seems to result from the
      establishment and persistence of plants in favorable microhabitats coupled with
      limited seed dispersal around maternal individuals. There were no differences in
      patterns of fine-scale genetic structure between protected and unprotected
      populations.

PMID- 15247311
TI  - Genetics of resistance to two strains of soybean mosaic virus in differential
      soybean genotypes.
AB  - There are seven pathotypes of soybean mosaic virus (SMV) representing seven
      strain groups (G1-G7) in the United States. Soybean genotypes [Glycine max (L.)
      Merr.] may exhibit resistant (R), susceptible (S), or necrotic (N) reactions upon
      interacting with different SMV strains. This research was conducted to
      investigate whether reactions to two SMV strains are controlled by the same gene
      or by separate genes. Two SMV-resistant soybean lines, LR1 and LR2, were crossed
      with the susceptible cultivar Lee 68. LR1 contains a resistance gene Rsv1-s and
      is resistant to strains G1-G4 and G7. LR2 contains the Rsv4 gene and is resistant
      to strains G1-G7. Two hundred F(2:3) lines from LR1 x Lee 68 and 262 F(2:3) lines
      from LR2 x Lee 68 were screened for SMV reaction. Seeds from each F2 plant were
      randomly divided into two subsamples. A minimum of 20 seeds from each subsample
      were planted in the greenhouse and plants were inoculated with either G1 or G7.
      G1 is the least virulent, whereas G7 is the most virulent strain of SMV. The
      results showed that all the F(2:3) lines from both crosses exhibited the same
      reaction to G1 and G7. No recombinants were found in all the progenies for
      reactions to G1 and G7 in either cross. The results indicate that reactions to
      both G1 and G7 are controlled by either the same gene or very closely linked
      genes. This research finding is valuable for studying the resistance mechanism
      and interactions of soybean genotypes and SMV strains and for breeding SMV
      resistance to multiple strains.

PMID- 15247313
TI  - Organization and variation of the mitochondrial control region in two vulture
      species, Gypaetus barbatus and Neophron percnopterus.
AB  - We report the first entire mitochondrial DNA (mtDNA) control region sequences in
      two endangered vulture species, the bearded vulture (Gypaetus barbatus) and the
      Egyptian vulture (Neophron percnopterus). Results showed that the general
      organization of vulture control regions was very similar to other birds, with
      three distinct domains: a left variable domain (DI), a central conserved one
      (DII) including the F, E, D, and C boxes, and a right domain (DIII) containing
      the CSB1 sequence. However, due to the presence of long tandem repeats, vulture
      control regions differed from other avian control regions both in size and
      nucleotide composition. The Egyptian vulture control region was found to be the
      largest sequenced so far (2031 bp), due to the simultaneous presence of repeats
      in both DI (80 bp) and DIII (77 bp). Low variation was found in vulture control
      regions, particularly in G. barbatus, as the probable result of populations
      declines in the last few centuries.

PMID- 15247312
TI  - Genetic diversity and relationships in native Hawaiian Saccharum officinarum
      sugarcane.
AB  - Commercial sugarcane hybrid cultivars currently in production are high-yielding,
      disease-resistant, millable canes and are the result of years of breeding work.
      In Hawaii, these commercial hybrids are quite distinct from many Saccharum
      officinarum canes still in existence that were brought to the islands and
      cultivated by the native Polynesians. The actual genetic relationships among the
      native canes and the extent to which they contributed to the commercial hybrid
      germplasm has been the subject of speculation over the years. Genetic analysis of
      43 presumed native Hawaiian S. officinarum clones using 228 DNA markers confirmed
      them to be a group distinct from the modern hybrid cultivars. The resulting
      dendrogram tended to confirm that there were several separate S. officinarum
      introductions that, owing to selections of somatic mutations, diverged into a
      number of cluster groups. When the "Sandwich Isles" were discovered by Captain
      James Cook in 1778, the Hawaiians were found to be growing sugarcane, S.
      officinarum ( Cook 1785). Sugarcane (ko, in the Hawaiian language) appeared in a
      variety of stalk and leaf colors, often with stripes (the "ribbon canes"). In the
      interest of preserving this historic germplasm, a collection was assembled in the
      1920s by Edward L. Caum of the Hawaiian Sugar Planters' Association and W. W. G.
      Moir of American Factors. Histories and descriptions of the canes were reported
      by Moir (1932).

PMID- 15247314
TI  - Marsupial MHC class II beta genes are not orthologous to the eutherian beta gene
      families.
AB  - The major histocompatibility complex (MHC) class II DRB, DQB, DPB, and DOB gene
      clusters are shared by different eutherian orders. Such an orthologous
      relationship is not seen between the beta genes of birds and eutherians. A high
      degree of uncertainty surrounds the evolutionary relationship of marsupial class
      II beta sequences with eutherian beta gene families. In particular, it has been
      suggested that marsupials utilize the DRB gene cluster. A cDNA encoding an MHC
      class II beta molecule was isolated from a brushtail possum mesenteric lymph node
      cDNA library. This clone is most similar to Macropus rufogriseus DBB. Our
      analysis suggests that all known marsupial beta-chain genes, excluding DMB, fall
      into two separate clades, which are distinct from the eutherian DRB, DQB, DPB, or
      DOB gene clusters. We recommend that the DAB and DBB nomenclature be reinstated.
      DAB and DBB orthologs are not present in eutherians. It appears that the
      marsupial and eutherian lineages have retained different gene clusters following
      gene duplication events early in mammalian evolution.

PMID- 15247315
TI  - Microsatellite marker development and analysis in the eastern oyster (Crassostrea
      virginica): confirmation of null alleles and non-Mendelian segregation ratios.
AB  - Eighteen microsatellite markers were developed for the Crassostrea virginica
      nuclear genome, including di-, tri-, and tetranucleotide microsatellite repeat
      regions that included perfect, imperfect, and compound repeat sequences. A
      reference panel with DNA from the parents and four progeny of 10 full-sib
      families was used for a preliminary confirmation of polymorphism at these loci
      and indications of null alleles. Null alleles were discovered at three loci; in
      two instances, primer redesign enabled their amplification. Two to five
      representative alleles from each locus were sequenced to ensure that the targeted
      loci were amplifying. The sequence analysis revealed not only variation in the
      number of simple sequence repeat units, but also polymorphisms in the
      microsatellite flanking regions. A total of 3626 bp of combined microsatellite
      flanking region from the 18 loci was examined, revealing indels as well as
      nucleotide site substitutions. Overall, 16 indels and 146 substitutions were
      found with an average of 4.5% polymorphism across all loci. Eight markers were
      tested on the parents and 39-61 progeny from each of four families for
      examination of allelic inheritance patterns and genotypic ratios. Twenty-six
      tests of segregation ratios revealed eight significant departures from expected
      Mendelian ratios, three of which remained significant after correction for
      multiple tests. Deviations were observed in both the directions of heterozygote
      excess and deficiency.

PMID- 15247316
TI  - Maternal inheritance of mitochondria in Eucalyptus globulus.
AB  - It is important to verify mitochondrial inheritance in plant species in which
      mitochondrial DNA (mtDNA) will be used as a source of molecular markers. We used
      a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP)
      approach to amplify mitochondrial introns from subunits 1, 4, 5, and 7 of NADH
      dehydrogenase (nad) and cytochrome oxidase subunit II (cox2) in Eucalyptus
      globulus. PCR fragments were then either sequenced or cut with restriction
      enzymes to reveal polymorphism. Sequencing cox2 showed that eucalypts lack the
      intron between exons 1 and 2. One polymorphism was found in intron 2-3 of nad7
      following restriction digests with HphI. Fifty-four F1 progeny from seven
      families with parents distinguishable in their mitochondrial nad7 were screened
      to show that mitochondria were maternally inherited in E. globulus. These results
      constitute the first report of mitochondrial inheritance in the family Myrtaceae.

PMID- 15247317
TI  - A case of recent long-distance dispersal in the Piriqueta caroliniana complex.
AB  - We investigated restriction fragment length polymorphism (RFLP) variation in the
      chloroplast DNA regions trnS and trnC in 53 populations of the herbaceous
      perennial Piriqueta caroliniana complex, encompassing its known North American
      range. The goals of this study were to expand the geographic range of a previous
      study and to determine the origin of an apparently anomalous population, which
      possessed a phenotype that was incongruous with other populations in the region.
      The phylogeography of these populations was investigated with nested clade
      analysis of a one-step network phylogeny that was based on the RFLP variation of
      the chloroplast genome. We found evidence of restricted gene flow and past
      fragmentation, which is consistent with a previous study on the phylogeography of
      this species complex. The morphological and genetic profile of the one anomalous
      population indicates that it recently originated from south Florida. Given the
      urban location of this geographically disjunct population, it is probable that
      this is an example of a recent human-mediated long-distance dispersal event.

PMID- 15247318
TI  - Nuclear import of HIV-1 integrase is inhibited in vitro by styrylquinoline
      derivatives.
AB  - Nuclear import of HIV-1 preintegration complexes (PICs) allows the virus to
      infect nondividing cells. Integrase (IN), the PIC-associated viral enzyme
      responsible for the integration of the viral genome into the host cell DNA,
      displays karyophilic properties and has been proposed to participate to the
      nuclear import of the PIC. Styrylquinolines (SQs) have been shown to block viral
      replication at nontoxic concentrations and to inhibit IN 3'-processing activity
      in vitro by competing with the DNA substrate binding. However, several lines of
      evidence suggested that SQs could have a postentry, preintegrative antiviral
      effect in infected cells. To gain new insights on the mechanism of their
      antiviral activity, SQs were assayed for their ability to affect nuclear import
      of HIV-1 IN and compared with the effect of a specific strand transfer inhibitor.
      Using an in vitro transport assay, we have previously shown that IN import is a
      saturable mechanism, thus showing that a limiting cellular factor is involved in
      this process. We now demonstrate that SQs specifically and efficiently inhibit in
      vitro nuclear import of IN without affecting other import pathways, whereas a
      specific strand transfer inhibitor does not affect IN import. These data suggest
      that SQs not only inhibit IN-DNA interaction but would also inhibit the
      interaction between IN and the cellular factor required for its nuclear import.

PMID- 15247319
TI  - The nicotinic receptor in the rat pineal gland is an alpha3beta4 subtype.
AB  - The rat pineal gland contains a high density of neuronal nicotinic acetylcholine
      receptors (nAChRs). We characterized the pharmacology of the binding sites and
      function of these receptors, measured the nAChR subunit mRNA, and used subunit
      specific antibodies to establish the receptor subtype as defined by subunit
      composition. In ligand binding studies, [3H]epibatidine ([3H]EB) binds with an
      affinity of approximately 100 pM to nAChRs in the pineal gland, and the density
      of these sites is approximately 5 times that in rat cerebral cortex. The
      affinities of nicotinic drugs for binding sites in the pineal gland are similar
      to those at alpha3beta4 nAChRs heterologously expressed in human embryonic kidney
      293 cells. In functional studies, the potencies and efficacies of nicotinic drugs
      to activate or block whole-cell currents in dissociated pinealocytes match
      closely their potencies and efficacies to activate or block 86Rb+ efflux in the
      cells expressing heterologous alpha3beta4 nAChRs. Measurements of mRNA indicated
      the presence of transcripts for alpha3, beta2, and beta4 nAChR subunits but not
      those for alpha2, alpha4, alpha5, alpha6, alpha7, or beta3 subunits.
      Immunoprecipitation with subunit-specific antibodies showed that virtually all
      [3H]EB-labeled nAChRs contained alpha3 and beta4 subunits associated in one
      complex. The beta2 subunit was not associated with this complex. Taken together,
      these results indicate that virtually all of the nAChRs in the rat pineal gland
      are the alpha3beta4 nAChR subtype and that the pineal gland can therefore serve
      as an excellent and convenient model in which to study the pharmacology and
      function of these receptors in a native tissue.

PMID- 15247320
TI  - Pentobarbital differentially modulates alpha1beta3delta and alpha1beta3gamma2L
      GABAA receptor currents.
AB  - GABAA receptors are modulated by a variety of compounds, including the
      neurosteroids and barbiturates. Although the effects of barbiturates on
      alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic
      inhibition, have been extensively studied, the effects of pentobarbital on
      kinetic properties of alphabetadelta GABAA receptors, thought to mediate tonic
      (extra- or perisynaptic) inhibition, are unknown. Using ultrafast drug delivery
      and single channel recording techniques, we demonstrate isoform-specific
      pentobarbital modulation of low-efficacy, minimally desensitizing alpha1beta3
      currents and high-efficacy, rapidly desensitizing alpha1beta3gamma2L currents.
      Specifically, with saturating concentrations of GABA, pentobarbital substantially
      potentiated peak alpha1beta3delta receptor currents but failed to potentiate peak
      alpha1beta3gamma2L receptor currents. Also, pentobarbital had opposite effects on
      the desensitization of alpha1beta3delta (increased) and alpha1beta3gamma2L
      (decreased) receptor currents evoked by saturating GABA. Pentobarbital increased
      steady-state alpha1beta3delta receptor single channel open duration primarily by
      introducing a longer duration open state, whereas for alpha1beta3gamma2L receptor
      channels, pentobarbital increased mean open duration by increasing the proportion
      and duration of the longest open state. The data support previous suggestions
      that GABA may be a partial agonist at alphabetadelta isoforms, which may render
      them particularly sensitive to allosteric modulation. The remarkable increase in
      gating efficacy of alpha1beta3delta receptors suggests that alphabetadelta
      isoforms, and by inference tonic forms of inhibition, may be important targets
      for barbiturates.

PMID- 15247321
TI  - RNAPol-ChIP: a novel application of chromatin immunoprecipitation to the analysis
      of real-time gene transcription.
AB  - We describe a procedure, RNAPol-ChIP, to measure actual transcriptional rate. It
      consists of the detection, by chromatin immunoprecipitation (ChIP), of RNA
      polymerase II within the coding region of genes. To do this, the DNA
      immunoprecipitated with polymerase antibodies is analysed by PCR, using an
      amplicon well within the coding region of the desired genes to avoid
      interferences with polymerase paused at the promoter. To validate RNAPol-ChIP, we
      compare our results to those obtained by classical methods in several genes
      induced during either liver regeneration or acute pancreatitis. When short half
      life mRNA genes are studied (e.g. c-fos and egr1), RNAPol-ChIP gives results
      similar to those of other procedures. However, in genes whose mRNA is more stable
      (e.g. the hemopexin, hpx, gene) RNAPol-ChIP informs on real-time transcription
      with results comparable to those of methods such as nuclear run-on or run-off,
      which require the isolation of highly purified nuclei. Moreover, RNAPol-ChIP
      advantageously compares with methods based on the analysis of steady-state mRNA
      (northern blot or RT-PCR). Additional advantages of RNAPol-ChIP, such as the
      possibility of combining it with classical ChIP analysis to study transcription
      associated changes in chromatin are discussed.

PMID- 15247322
TI  - A GFP-based assay for rapid screening of compounds affecting ARE-dependent mRNA
      turnover.
AB  - A reporter transcript containing the green fluorescent protein (GFP) gene
      upstream of the destabilizing 3'-untranslated region (3'-UTR) of the murine IL-3
      gene was inserted in mouse PB-3c-15 mast cells. The GFP-IL-3 transcript was
      inherently unstable due to the presence of an adenosine-uridine (AU)-rich element
      (ARE) in the 3'-UTR and was subject to rapid decay giving a low baseline of GFP
      fluorescence. Transcript stabilization with ionomycin resulted in an increase of
      fluorescence that is quantitated by FACS analysis of responding cells. Using this
      system we have identified okadaic acid as a novel stabilizing compound, and
      investigated the upstream signaling pathways leading to stabilization. This
      reporter system has the advantage of speed and simplicity over standard methods
      currently in use and in addition to serving as a research tool it can be easily
      automated to increase throughput for drug discovery.

PMID- 15247323
TI  - Structural analysis of hepatitis C RNA genome using DNA microarrays.
AB  - Many studies have tried to identify specific nucleotide sequences in the
      quasispecies of hepatitis C virus (HCV) that determine resistance or sensitivity
      to interferon (IFN) therapy, unfortunately without conclusive results. Although
      viral proteins represent the most evident phenotype of the virus, genomic RNA
      sequences determine secondary and tertiary structures which are also part of the
      viral phenotype and can be involved in important biological roles. In this work,
      a method of RNA structure analysis has been developed based on the hybridization
      of labelled HCV transcripts to microarrays of complementary DNA oligonucleotides.
      Hybridizations were carried out at non-denaturing conditions, using appropriate
      temperature and buffer composition to allow binding to the immobilized probes of
      the RNA transcript without disturbing its secondary/tertiary structural motifs.
      Oligonucleotides printed onto the microarray covered the entire 5' non-coding
      region (5'NCR), the first three-quarters of the core region, the E2-NS2 junction
      and the first 400 nt of the NS3 region. We document the use of this methodology
      to analyse the structural degree of a large region of HCV genomic RNA in two
      genotypes associated with different responses to IFN treatment. The results
      reported here show different structural degree along the genome regions analysed,
      and differential hybridization patterns for distinct genotypes in NS2 and NS3 HCV
      regions.

PMID- 15247324
TI  - A novel 4-base-recognizing RNA cutter that can remove the single 3' terminal
      nucleotides from RNA molecules.
AB  - Mammalian tRNase ZL shows versatility in substrate recognition. This enzyme can
      not only process pre-tRNAs by cleaving off their 3' trailer sequences, but also
      recognize and cleave pre-tRNA-like complexes and micro-pre-tRNAs. Here we
      demonstrate that 24-27 nt hairpin RNAs (hook RNAs) can guide cleavages of
      separate target RNAs by tRNase ZL through the micro-pre-tRNA-like complexes
      between the targets and the hook RNAs and that tRNase ZL together with hook RNA
      works as 4-7-base-recognizing RNA cutters. The cleavage sites were located only
      after the nucleotide corresponding to the discriminator nucleotide. Cleavage
      assays for various substrate/hooker complexes showed that the cleavage efficiency
      changes depending on the maximum number of substrate/hooker recognition base
      pairings and the stem length of hook RNA and that a 5 nt recognition sequence and
      a hook RNA containing a 6 or 7 bp stem are the best combination for the optimal
      target cleavage. We also show that a 4-base RNA cutter can remove the single 3'
      terminal nucleotides from RNA molecules. These results indicate that this new
      type of RNA cutter can be utilized to homogenize at their 3' termini RNA
      transcripts synthesized in vitro with a bacteriophage RNA polymerase.

PMID- 15247325
TI  - Elimination of background recombination: somatic induction of Cre by combined
      transcriptional regulation and hormone binding affinity.
AB  - Somatically inducible Cre lines are used extensively to study gene function.
      However, a background level of spontaneous recombination due to unregulated
      expression of Cre is particularly confounding for cancer models in which
      following the pathogenesis of the disease requires the introduction of sporadic
      mutations that are monitored over time. In three transgenic mouse lines, two with
      Cre activity controlled at the transcriptional level (Ahcre, Mx1cre), and one
      controlled at the protein level (R26creER(T)), we have identified sporadic
      recombination at the R26R reporter locus in multiple tissues. Detailed analysis
      of the intestinal epithelium suggests that recombination can occur both during
      development and as an ongoing process in adult life. Here we present a new
      inducible Cre transgenic line, AhcreER(T), in which control of Cre activity is
      regulated at two levels: by transcriptional control of the Ah promoter and by a
      requirement for Tamoxifen binding. There is no detectable background intestinal
      recombination in adult AhcreER(T) mice on the R26R background. Inducible and dose
      dependent recombination can be achieved by a single combined treatment with beta
      napthoflavone and Tamoxifen.

PMID- 15247326
TI  - A method for cross-species gene expression analysis with high-density
      oligonucleotide arrays.
AB  - DNA microarrays have been widely used in gene expression analysis of biological
      processes. Due to a lack of sequence information, the applications have been
      largely restricted to humans and a few model organisms. Presented within this
      study are results of the cross-species hybridization with Affymetrix human high
      density oligonucleotide arrays or GeneChip using distantly related mammalian
      species; cattle, pig and dog. Based on the unique feature of the Affymetrix
      GeneChip where every gene is represented by multiple probes, we hypothesized that
      sequence conservation within mammals is high enough to generate sufficient
      signals from some of the probes for expression analysis. We demonstrated that
      while overall hybridization signals are low for cross-species hybridization, a
      few probes of most genes still generated signals equivalent to the same-species
      hybridization. By masking the poorly hybridized probes electronically, the
      remaining probes provided reliable data for gene expression analysis. We
      developed an algorithm to select the reliable probes for analysis utilizing the
      match/mismatch feature of GeneChip. When comparing gene expression between two
      tissues using the selected probes, we found a linear correlation between the
      cross-species and same-species hybridization. In addition, we validated cross
      species hybridization results by quantitative PCR using randomly selected genes.
      The method shown herein could be applied to both plant and animal research.

PMID- 15247327
TI  - Generation of longer 3' cDNA fragments from massively parallel signature
      sequencing tags.
AB  - Massively Parallel Signature Sequencing (MPSS) is a powerful technique for genome
      wide gene expression analysis, which, similar to SAGE, relies on the production
      of short tags proximal to the 3'end of transcripts. A single MPSS experiment can
      generate over 10(7) tags, providing a 10-fold coverage of the transcripts
      expressed in a human cell. A significant fraction of MPSS tags cannot be assigned
      to known transcripts (orphan tags) and are likely to be derived from transcripts
      expressed at very low levels (approximately 1 copy per cell). In order to explore
      the potential of MPSS for the characterization of the human transcriptome, we
      have adapted the GLGI protocol (Generation of Longer cDNA fragments from SAGE
      tags for Gene Identification) to convert MPSS tags into their corresponding 3'
      cDNA fragments. GLGI-MPSS was applied to 83 orphan tags and 41 cDNA fragments
      were obtained. The analysis of these 41 fragments allowed the identification of
      novel transcripts, alternative tags generated from polymorphic and alternatively
      spliced transcripts, as well as the detection of artefactual MPSS tags. A
      systematic large-scale analysis of the genome by MPSS, in combination with the
      use of GLGI-MPSS protocol, will certainly provide a complementary approach to
      generate the complete catalog of human transcripts.

PMID- 15247328
TI  - In vitro selection of restriction endonucleases by in vitro compartmentalization.
AB  - Restriction endonucleases are widely used in laboratory applications from
      recombinant DNA technology to diagnostics, but engineering of restriction enzymes
      by structure-guided design and in vivo directed evolution is at an early stage.
      Here, we report the use of an in vitro compartmentalization system for completely
      in vitro selection of restriction enzymes. Compartmentalization of a single gene
      in a rabbit reticulocyte in vitro transcription/translation system serves to
      isolate individually synthesized enzymes from each other. In each compartment, an
      active enzyme cleaves only its own encoding gene, whereas genes encoding inactive
      enzymes remain intact. Affinity selection of the cleaved DNA encoding active
      restriction endonucleases was accomplished by the use of streptavidin-immobilized
      beads and dUTP-biotin, which was efficiently incorporated into the cohesive end
      of the cleaved DNA using a DNA polymerase. We confirmed that genes encoding
      active restriction endonuclease FokI could be selected from a randomized library.
      This method overcomes the limitations of current in vivo technologies and should
      prove useful for rapid screening and evolution of novel restriction enzymes from
      diverse mutant libraries, as well as for studies of catalytic and evolutionary
      mechanisms of restriction enzymes.

PMID- 15247329
TI  - Increasing the efficiency of SAGE adaptor ligation by directed ligation
      chemistry.
AB  - The ability of Serial Analysis of Gene Expression (SAGE) to provide a
      quantitative picture of global gene expression relies not only on the depth and
      accuracy of sequencing into the SAGE library, but also on the efficiency of each
      step required to generate the SAGE library from the starting mRNA material. The
      first critical step is the ligation of adaptors containing a Type IIS recognition
      sequence to the anchored 3' end cDNA population that permits the release of short
      sequence tags (SSTs) from defined sites within the 3' end of each transcript.
      Using an in vitro transcript as a template, we observed that only a small
      fraction of anchored 3' end cDNA are successfully ligated with added SAGE
      adaptors under typical reaction conditions currently used in the SAGE protocol.
      Although the introduction of approximately 500-fold molar excess of adaptor or
      the inclusion of 15% (w/v) PEG-8000 increased the yield of the adaptor-modified
      product, complete conversion to the desired adaptor:cDNA hetero-ligation product
      is not achieved. An alternative method of ligation, termed as directed ligation,
      is described which exploits a favourable mass-action condition created by the
      presence of NlaIII during ligation in combination with a novel SAGE adaptor
      containing a methylated base within the ligation site. Using this strategy, we
      were able to achieve near complete conversion of the anchored 3' end cDNA into
      the desired adaptor-modified product. This new protocol therefore greatly
      increases the probability that a SST will be generated from every transcript,
      greatly enhancing the fidelity of SAGE. Directed ligation also provides a
      powerful means to achieve near-complete ligation of any appropriately designed
      adaptor to its respective target.

PMID- 15247331
TI  - Strain-specific telomere length revealed by single telomere length analysis in
      Caenorhabditis elegans.
AB  - Terminal restriction fragment analysis is the only method currently available for
      measuring telomere length in Caenorhabditis elegans. Its limitations include low
      sensitivity and interference by the presence of interstitial telomeric sequences
      in the C.elegans genome. Here we report the adaptation of single telomere length
      analysis (STELA) to measure the length of telomeric repeats on the left arm of
      chromosome V in C.elegans. This highly sensitive PCR-based method allows telomere
      length measurement from as few as a single worm. The application of STELA to
      eight wild-type C.elegans strains revealed considerable strain-specific
      differences in telomere length. Within individual strains, short outlying
      telomeres were observed that were clearly distinct from the bulk telomere length
      distributions, suggesting that processes other than end-replication losses and
      telomerase-mediated lengthening may generate telomere length heterogeneity in
      C.elegans. The utility of this method was further demonstrated by the
      characterization of telomere shortening in mrt-2 mutants. We conclude that STELA
      appears to be a valuable tool for studying telomere biology in C.elegans.

PMID- 15247330
TI  - Tissue-specific and imprinted epigenetic modifications of the human NDN gene.
AB  - Allele-specific DNA methylation, histone acetylation and histone methylation are
      recognized as epigenetic characteristics of imprinted genes and imprinting
      centers (ICs). These epigenetic modifications are also used to regulate tissue
      specific gene expression. Epigenetic differences between alleles can be
      significant either in the function of the IC or in the cis-acting effect of the
      IC on 'target' genes responding to it. We have now examined the epigenetic
      characteristics of NDN, a target gene of the chromosome 15q11-q13 Prader-Willi
      Syndrome IC, using sodium bisulfite sequencing to analyze DNA methylation and
      chromatin immunoprecipitation to analyze histone modifications. We observed a
      bias towards maternal allele-specific DNA hypermethylation of the promoter CpG
      island of NDN, independent of tissue-specific transcriptional activity. We also
      found that NDN lies in a domain of paternal allele-specific histone
      hyperacetylation that correlates with transcriptional state, and a domain of
      differential histone H3 lysine 4 di- and tri-methylation that persists
      independent of transcription. These results suggest that DNA methylation and
      histone H3 lysine 4 methylation are persistent markers of imprinted gene
      regulation while histone acetylation participates in tissue-specific activity and
      silencing in somatic cells.

PMID- 15247332
TI  - A probabilistic model of 3' end formation in Caenorhabditis elegans.
AB  - The 3' ends of mRNAs terminate with a poly(A) tail. This post-transcriptional
      modification is directed by sequence features present in the 3'-untranslated
      region (3'-UTR). We have undertaken a computational analysis of 3' end formation
      in Caenorhabditis elegans. By aligning cDNAs that diverge from genomic sequence
      at the poly(A) tract, we accurately identified a large set of true cleavage
      sites. When there are many transcripts aligned to a particular locus, local
      variation of the cleavage site over a span of a few bases is frequently observed.
      We find that in addition to the well-known AAUAAA motif there are several regions
      with distinct nucleotide compositional biases. We propose a generalized hidden
      Markov model that describes sequence features in C.elegans 3'-UTRs. We find that
      a computer program employing this model accurately predicts experimentally
      observed 3' ends even when there are multiple AAUAAA motifs and multiple cleavage
      sites. We have made available a complete set of polyadenylation site predictions
      for the C.elegans genome, including a subset of 6570 supported by aligned
      transcripts.

PMID- 15247333
TI  - DNA sequence recognition by an isopropyl substituted thiazole polyamide.
AB  - We have used DNA footprinting and fluorescence melting experiments to study the
      sequence-specific binding of a novel minor groove binding ligand (thiazotropsin
      A), containing an isopropyl substituted thiazole polyamide, to DNA. In one
      fragment, which contains every tetranucleotide sequence, sub-micromolar
      concentrations of the ligand generate a single footprint at the sequence ACTAGT.
      This sequence preference is confirmed in melting experiments with fluorescently
      labelled oligonucleotides. Experiments with DNA fragments that contain variants
      of this sequence suggest that the ligand also binds, with slightly lower
      affinity, to sequences of the type XCYRGZ, where X is any base except C, and Z is
      any base except G.

PMID- 15247334
TI  - Extending the classification of bacterial transcription factors beyond the helix
      turn-helix motif as an alternative approach to discover new cis/trans
      relationships.
AB  - Transcription factors (TFs) of bacterial helix-turn-helix superfamilies exhibit
      different effector-binding domains (EBDs) fused to a DNA-binding domain with a
      common feature. In a previous study of the GntR superfamily, we demonstrated that
      classifying members into subfamilies according to the EBD heterogeneity
      highlighted unsuspected and accurate TF-binding site signatures. In this work, we
      present how such in silico analysis can provide prediction tools to discover new
      cis/trans relationships. The TF-binding site consensus of the HutC/GntR subfamily
      was used to (i) predict target sites within the Streptomyces coelicolor genome,
      (ii) discover a new HutC/GntR regulon and (iii) discover its specific TF. By
      scanning the S.coelicolor genome we identified a presumed new HutC regulon that
      comprises genes of the phosphotransferase system (PTS) specific for the uptake of
      N-acetylglucosamine (PTS(Nag)). A weight matrix was derived from the compilation
      of the predicted cis-acting elements upstream of each gene of the presumed
      regulon. Under the assumption that TFs are often subject to autoregulation, we
      used this matrix to scan the upstream region of the 24 HutC-like members of
      S.coelicolor. orf SCO5231 (dasR) was selected as the best candidate according to
      the high score of a 16 bp sequence identified in its upstream region. Our
      prediction that DasR regulates the PTS(Nag) regulon was confirmed by in vivo and
      in vitro experiments. In conclusion, our in silico approach permitted to
      highlight the specific TF of a regulon out of the 673 orfs annotated as
      'regulatory proteins' within the genome of S.coelicolor.

PMID- 15247335
TI  - Thermodynamic and structural characterization of 2'-nitrogen-modified RNA
      duplexes.
AB  - 2'-aminonucleosides are commonly used as sites of post-synthetic chemical
      modification within nucleic acids. As part of a larger cross-linking strategy, we
      appended alkyl groups onto the N2' position of 2'-amino-modified RNAs via 2'
      ureido and 2'-amido linkages. We have characterized the thermodynamics of 2'
      amino, 2'-alkylamido and 2'-alkylureido-modified RNA duplexes and show that 2'
      ureido-modified RNAs are significantly more stable than analogous 2'-amido
      modified RNAs. Using NMR spectroscopy and NMR-based molecular modeling of 2'
      modified RNA duplexes, we examined the effects that 2'-nitrogen modifications
      have on RNA helices. Our data suggest that the 2'-ureido group forms a specific
      intra-nucleoside interaction that cannot occur within 2'-amido-modified helices.
      These results indicate that 2'-ureido modifications are superior to analogous 2'
      amido ones for applications that require stable base pairing.

PMID- 15247336
TI  - Binding of phage Phi29 architectural protein p6 to the viral genome: evidence for
      topological restriction of the phage linear DNA.
AB  - Bacillus subtilis phage Phi29 protein p6 is required for DNA replication and
      promotes the switch from early to late transcription. In vivo it binds all along
      the viral linear DNA, which suggests a global role as an architectural protein;
      in contrast, binding to bacterial DNA is negligible. This specificity could be
      due to the p6 binding preference for less negatively supercoiled DNA, as is
      presumably the case with viral (with respect to bacterial) DNA. Here we
      demonstrate that p6 binding to Phi29 DNA is greatly increased when negative
      supercoiling is decreased by novobiocin; in addition, gyrase is required for DNA
      replication. This indicates that, although non-covalently closed, the viral
      genome is topologically constrained in vivo. We also show that the p6 binding to
      different Phi29 DNA regions is modulated by the structural properties of their
      nucleotide sequences. The higher affinity for DNA ends is possibly related to the
      presence of sequences in which their bendability properties favor the formation
      of the p6-DNA complex, whereas the lower affinity for the transcription control
      region is most probably due to the presence of a rigid intrinsic DNA curvature.

PMID- 15247337
TI  - Antiretroviral agents--how best to protect infants from HIV and save their
      mothers from AIDS.

PMID- 15247338
TI  - Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to
      child transmission of HIV-1 in Thailand.
AB  - BACKGROUND: Although zidovudine prophylaxis decreases the rate of transmission of
      the human immunodeficiency virus (HIV) type 1 substantially, a large number of
      infants still become infected. We hypothesized that the administration, in
      addition to zidovudine, of a single dose of oral nevirapine to mothers during
      labor and to neonates would further reduce transmission of HIV. METHODS: We
      conducted a randomized, double-blind trial of three treatment regimens in Thai
      women who were receiving zidovudine therapy during the third trimester of
      pregnancy. In one group, mothers and infants received a single dose of nevirapine
      (nevirapine-nevirapine regimen); in another, mothers and infants received
      nevirapine and placebo, respectively (nevirapine-placebo regimen); and in the
      last, mothers and infants received placebo (placebo-placebo regimen). The infants
      also received one week of zidovudine therapy and were formula-fed. The end point
      of the study was infection with HIV in the infants, established by virologic
      testing. RESULTS: Between January 15, 2001, and February 28, 2003, a total of
      1844 Thai women were enrolled. At the first interim analysis, the independent
      data monitoring committee stopped enrollment in the placebo-placebo group. Among
      women who delivered before the interim analysis, the as-randomized Kaplan-Meier
      estimates of the transmission rates were 1.1 percent (95 percent confidence
      interval, 0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95
      percent confidence interval, 3.8 to 8.9) in the placebo-placebo group (P<0.001).
      The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9
      percent (95 percent confidence interval, 0.9 to 3.0), was not significantly
      inferior to the rate in the nevirapine-placebo group (2.8 percent; 95 percent
      confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups
      defined by known risk factors such as viral load and CD4 count. No serious
      adverse effects were associated with nevirapine therapy. CONCLUSIONS: A single
      dose of nevirapine to the mother, with or without a dose of nevirapine to the
      infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is
      highly effective in reducing mother-to-child transmission of HIV.

PMID- 15247339
TI  - Intrapartum exposure to nevirapine and subsequent maternal responses to
      nevirapine-based antiretroviral therapy.
AB  - BACKGROUND: A single intrapartum dose of nevirapine for the prevention of mother
      to-child transmission of human immunodeficiency virus (HIV) leads to the
      selection of resistance mutations. Whether there are clinically significant
      consequences in mothers who are subsequently treated with a nevirapine-containing
      regimen is unknown. METHODS: We randomly assigned 1844 women in Thailand who
      received zidovudine during the third trimester of pregnancy to receive
      intrapartum nevirapine or placebo. In the postpartum period, 269 of the women
      with a CD4 count below 250 cells per cubic millimeter began a nevirapine
      containing antiretroviral regimen. Plasma samples were obtained 10 days post
      partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was
      measured before the initiation of therapy and three and six months thereafter.
      RESULTS: After six months of therapy, the HIV-1 RNA level was less than 50 copies
      per milliliter in 49 percent of the women who had received intrapartum
      nevirapine, as compared with 68 percent of the women who had not received
      intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse
      transcriptase inhibitors were detectable in blood samples obtained 10 days post
      partum from 32 percent of the women who had received intrapartum nevirapine; the
      most frequent mutations were K103N, G190A, and Y181C. Among the women who had
      received intrapartum nevirapine, viral suppression was achieved at six months in
      38 percent of those with resistance mutations and 52 percent of those without
      resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53
      log10 copies per milliliter before therapy and intrapartum exposure to nevirapine
      were independently associated with virologic failure. After six months of
      therapy, there was no significant difference between groups in the CD4 count
      (P=0.65). CONCLUSIONS: Women who received intrapartum nevirapine were less likely
      to have virologic suppression after six months of postpartum treatment with a
      nevirapine-containing regimen. Our data suggest the need for strategies to
      maximize the benefits of both antiretroviral prophylaxis against mother-to-child
      transmission of HIV and antiretroviral therapy for mothers.

PMID- 15247341
TI  - Packaging motor from double-stranded RNA bacteriophage phi12 acts as an
      obligatory passive conduit during transcription.
AB  - Double-stranded RNA viruses sequester their genomes within a protein shell,
      called the polymerase complex. Translocation of ssRNA into (packaging) and out
      (transcription) of the polymerase complex are essential steps in the life cycle
      of the dsRNA bacteriophages of the Cystoviridae family (phi6-phi14). Both
      processes require a viral molecular motor P4, an NTPase, which bears structural
      and functional similarities to hexameric helicases. In effect, switching between
      the packaging and the transcription mode requires the translocation direction of
      the P4 motor to reverse. However, the mechanism of the reversal remains elusive.
      Here we characterize the P4 protein from bacteriophage phi12 and exploit its
      purine nucleotide specificity to delineate P4 role in transcription. The results
      indicate that while P4 actively translocates RNA during packaging it acts as a
      passive conduit for RNA export. The directionality switching is accomplished via
      the regulation of P4 NTPase activity within the polymerase core.

PMID- 15247342
TI  - APE1 is the major 3'-phosphoglycolate activity in human cell extracts.
AB  - DNA strand breaks containing 3'-phosphoglycolate (3'-PG) ends are the major
      lesions induced by ionizing radiation. The repair of this lesion is not
      completely understood and several activities are thought to be involved in
      processing of 3'-PG ends. In this study we examined activities in human whole
      cell extracts (WCE) responsible for removal of 3'-PG. Using a radiolabelled
      oligonucleotide containing a single nucleotide gap with internal 5'-phosphate and
      3'-PG ends, we demonstrate that the major 3'-PG activity in human WCE is Mg2+
      dependent and that this activity co-purifies with AP endonuclease 1 (APE1) over
      phosphocellulose and gel filtration chromatography. Furthermore, immunodepletion
      of APE1 from active gel filtration fractions using APE1 specific antibodies
      reveals that the major activity against 3'-PG in human WCE is APE1.

PMID- 15247343
TI  - Reverse gyrase has heat-protective DNA chaperone activity independent of
      supercoiling.
AB  - Hyperthermophilic organisms must protect their constituent macromolecules from
      heat-induced degradation. A general mechanism for thermoprotection of DNA in
      active cells is unknown. We show that reverse gyrase, the only protein that is
      both specific and common to all hyperthermophiles, reduces the rate of double
      stranded DNA breakage approximately 8-fold at 90 degrees C. This activity does
      not require ATP hydrolysis and is independent of the positive supercoiling
      activity of the enzyme. Reverse gyrase has a minor nonspecific effect on the rate
      of depurination, and a major specific effect on the rate of double-strand
      breakage. Using electron microscopy, we show that reverse gyrase recognizes
      nicked DNA and recruits a protein coat to the site of damage through cooperative
      binding. Analogously to molecular chaperones that assist unfolded proteins, we
      found that reverse gyrase prevents inappropriate aggregation of denatured DNA
      regions and promotes correct annealing. We propose a model for a targeted
      protection mechanism in vivo in which reverse gyrase detects damaged DNA and acts
      as a molecular splint to prevent DNA breakage in the vicinity of the lesion, thus
      maintaining damaged DNA in a conformation that is amenable to repair.

PMID- 15247344
TI  - Lack of homologous sequence-specific DNA methylation in response to stable dsRNA
      expression in mouse oocytes.
AB  - Double-stranded RNA (dsRNA) induces sequence-specific mRNA degradation in most
      eukaryotic organisms via a conserved pathway known as RNA interference (RNAi).
      Post-transcriptional gene silencing by RNAi is also connected with
      transcriptional silencing of cognate sequences. In plants, this transcriptional
      silencing is associated with sequence-specific DNA methylation. To address
      whether this mechanism operates in mammalian cells, we used bisulfite sequencing
      to analyze DNA in mouse oocytes constitutively expressing long dsRNA against the
      Mos gene. Our data show that long dsRNA induces efficient Mos mRNA knockdown but
      not CpG and non-CpG DNA methylation of the endogenous Mos sequence in oocytes and
      early embryos. These data demonstrate that dsRNA does not directly induce DNA
      methylation in the trans form of this sequence in these mammalian cells.

PMID- 15247345
TI  - A phage display selection of engrailed homeodomain mutants and the importance of
      residue Q50.
AB  - Mutants of engrailed homeodomain (HD) that retain DNA-binding activity were
      isolated using a phage display selection. This selection was used to enrich for
      active DNA-binding clones from a complex library consisting of over a billion
      members. A more focused library of mutant homeodomains consisting of all possible
      amino acid combinations at two DNA-contacting residues (I47 and Q50) was
      constructed and screened for members capable of binding tightly and specifically
      to the engrailed consensus sequence, TAATTA. The isolated mutants largely
      recapitulated the distribution of amino acids found at these positions in natural
      homeodomains thus validating the in vitro selection conditions. In particular,
      the unequivocal advantage enjoyed by glutamine at residue 50 is surprising in
      light of reports that minimize the importance of this residue. Here, the subtle
      contributions of residue Q50 are demonstrated to play a functionally important
      role in specific recognition of DNA. These results highlight the complex subtlety
      of protein-DNA interactions, underscoring the value of the first reported in
      vitro selection of a homeodomain.

PMID- 15247346
TI  - Synthesis and characterization of oligonucleotides containing conformationally
      constrained bicyclo[3.1.0]hexane pseudosugar analogs.
AB  - Oligodeoxyribonucleotides containing pseudorotationally locked sites derived from
      bicyclo[3.1.0]hexane pseudosugars have been synthesized using adenosine,
      thymidine and abasic versions of North- and South-methanocarba nucleosides. The
      reaction conditions for coupling and oxidation steps of oligonucleotide synthesis
      have been investigated and optimized to allow efficient and facile solid-phase
      synthesis using phosphoramidite chemistry. Our studies demonstrate that the use
      of iodine for P(III) to P(V) oxidation leads to strand cleavage at the sites
      where the pseudosugar is North. In contrast, the same cleavage reaction was not
      observed in the case of South pseudosugars. Iodine oxidation generates a 5'
      phosphate oligonucleotide fragment on the resin and releases the North
      pseudosugar into the solution. This side reaction, which is responsible for the
      extremely low yields observed for the incorporation of the North pseudosugar
      analogs, has been studied in detail and can be easily overcome by replacing
      iodine with t-butylhydroperoxide as oxidant.

PMID- 15247348
TI  - The isolation of strand-specific nicking endonucleases from a randomized SapI
      expression library.
AB  - The Type IIS restriction endonuclease SapI recognizes the DNA sequence 5'-GCTCTTC
      3' (top strand by convention) and cleaves downstream (N1/N4) indicating top- and
      bottom-strand spacing, respectively. The asymmetric nature of DNA recognition
      presented the possibility that one, if not two, nicking variants might be created
      from SapI. To explore this possibility, two parallel selection procedures were
      designed to isolate either top-strand nicking or bottom-strand nicking variants
      from a randomly mutated SapI expression library. These procedures take advantage
      of a SapI substrate site designed into the expression plasmid, which allows for
      in vitro selection of plasmid clones possessing a site-specific and strand
      specific nick. A procedure designed to isolate bottom-strand nicking enzymes
      yielded Nb.SapI-1 containing a critical R420I substitution near the end of the
      protein. The top-strand procedure yielded several SapI variants with a distinct
      preference for top-strand cleavage. Mutations present within the selected clones
      were segregated to confirm a top-strand nicking phenotype for single variants
      Q240R, E250K, G271R or K273R. The nature of the amino acid substitutions found in
      the selected variants provides evidence that SapI may possess two active sites
      per monomer. This work presents a framework for establishing the mechanism of
      SapI DNA cleavage.

PMID- 15247349
TI  - The AIDS epidemic in 2004.

PMID- 15247347
TI  - A set of BAC clones spanning the human genome.
AB  - Using the human bacterial artificial chromosome (BAC) fingerprint-based physical
      map, genome sequence assembly and BAC end sequences, we have generated a
      fingerprint-validated set of 32 855 BAC clones spanning the human genome. The
      clone set provides coverage for at least 98% of the human fingerprint map, 99% of
      the current assembled sequence and has an effective resolving power of 79 kb. We
      have made the clone set publicly available, anticipating that it will generally
      facilitate FISH or array-CGH-based identification and characterization of
      chromosomal alterations relevant to disease.

PMID- 15247350
TI  - HIV and AIDS in the Former Soviet Bloc.

PMID- 15247351
TI  - Anthracycline cardiotoxicity in children.

PMID- 15247352
TI  - Syphilis control--a continuing challenge.

PMID- 15247353
TI  - Preoperative PSA velocity and the risk of death from prostate cancer after
      radical prostatectomy.
AB  - BACKGROUND: We evaluated whether men at risk for death from prostate cancer after
      radical prostatectomy can be identified using information available at diagnosis.
      METHODS: We studied 1095 men with localized prostate cancer to assess whether the
      rate of rise in the prostate-specific antigen (PSA) level--the PSA velocity-
      during the year before diagnosis, the PSA level at diagnosis, the Gleason score,
      and the clinical tumor stage could predict the time to death from prostate cancer
      and death from any cause after radical prostatectomy. RESULTS: As compared with
      an annual PSA velocity of 2.0 ng per milliliter or less, an annual PSA velocity
      of more than 2.0 ng per milliliter was associated with a significantly shorter
      time to death from prostate cancer (P<0.001) and death from any cause (P=0.01).
      An increasing PSA level at diagnosis (P=0.01), a Gleason score of 8, 9, or 10
      (P=0.02), and a clinical tumor stage of T2 (P<0.001) also predicted the time to
      death from prostate cancer. For men with an annual PSA velocity of more than 2.0
      ng per milliliter, estimates of the risk of death from prostate cancer and death
      from any cause seven years after radical prostatectomy were also influenced by
      the PSA level, tumor stage, and Gleason score at diagnosis. CONCLUSIONS: Men
      whose PSA level increases by more than 2.0 ng per milliliter during the year
      before the diagnosis of prostate cancer may have a relatively high risk of death
      from prostate cancer despite undergoing radical prostatectomy.

PMID- 15247354
TI  - The effect of dexrazoxane on myocardial injury in doxorubicin-treated children
      with acute lymphoblastic leukemia.
AB  - BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute
      lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a
      free-radical scavenger, may protect the heart from doxorubicin-associated damage.
      METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury
      of cardiomyocytes, we randomly assigned 101 children with ALL to receive
      doxorubicin alone (30 mg per square meter of body-surface area every three weeks
      for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed
      immediately by doxorubicin. Serial measurements of serum cardiac troponin T were
      obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in
      the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean,
      15.1 samples per patient) were obtained before, during, and after treatment with
      doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine
      whether they were elevated (>0.01 ng per milliliter)--the primary end point--or
      extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T
      occurred in 35 percent of the patients (55 of 158). Patients treated with
      doxorubicin alone were more likely than those who received dexrazoxane and
      doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent,
      P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent,
      P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at
      2.5 years was 83 percent in both groups (P=0.87 by the log-rank test).
      CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by
      elevations in troponin T, that is associated with the use of doxorubicin for
      childhood ALL without compromising the antileukemic efficacy of doxorubicin.
      Longer follow-up will be necessary to determine the influence of dexrazoxane on
      echocardiographic findings at four years and on event-free survival.

PMID- 15247355
TI  - Macrolide resistance in Treponema pallidum in the United States and Ireland.

PMID- 15247356
TI  - Acute renal failure and sepsis.

PMID- 15247357
TI  - Images in clinical medicine. Circumpapillary retinal ridge in the shaken-baby
      syndrome.

PMID- 15247358
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 21-2004. A 63-year-old man with metastatic prostate carcinoma
      refractory to hormone therapy.

PMID- 15247359
TI  - Progress toward identifying aggressive prostate cancer.

PMID- 15247360
TI  - Sparking the failing heart.

PMID- 15247361
TI  - Cinacalcet for secondary hyperparathyroidism in hemodialysis recipients.

PMID- 15247362
TI  - Ten years of alendronate treatment for osteoporosis in postmenopausal women.

PMID- 15247363
TI  - God at the bedside.

PMID- 15247364
TI  - Infections associated with surgical implants.

PMID- 15247365
TI  - Bone metastasis.

PMID- 15247366
TI  - Pemberton's sign.

PMID- 15247367
TI  - Bone lesions in molecular subtypes of multiple myeloma.

PMID- 15247368
TI  - Images in clinical medicine. Swinging heart.

PMID- 15247369
TI  - Salt cress. A halophyte and cryophyte Arabidopsis relative model system and its
      applicability to molecular genetic analyses of growth and development of
      extremophiles.
AB  - Salt cress (Thellungiella halophila) is a small winter annual crucifer with a
      short life cycle. It has a small genome (about 2 x Arabidopsis) with high
      sequence identity (average 92%) with Arabidopsis, and can be genetically
      transformed by the simple floral dip procedure. It is capable of copious seed
      production. Salt cress is an extremophile native to harsh environments and can
      reproduce after exposure to extreme salinity (500 mm NaCl) or cold to -15 degrees
      C. It is a typical halophyte that accumulates NaCl at controlled rates and also
      dramatic levels of Pro (>150 mm) during exposure to high salinity. Stomata of
      salt cress are distributed on the leaf surface at higher density, but are less
      open than the stomata of Arabidopsis and respond to salt stress by closing more
      tightly. Leaves of salt cress are more succulent-like, have a second layer of
      palisade mesophyll cells, and are frequently shed during extreme salt stress.
      Roots of salt cress develop both an extra endodermis and cortex cell layer
      compared to Arabidopsis. Salt cress, although salt and cold tolerant, is not
      exceptionally tolerant of soil desiccation. We have isolated several ethyl
      methanesulfonate mutants of salt cress that have reduced salinity tolerance,
      which provide evidence that salt tolerance in this halophyte can be significantly
      affected by individual genetic loci. Analysis of salt cress expressed sequence
      tags provides evidence for the presence of paralogs, missing in the Arabidopsis
      genome, and for genes with abiotic stress-relevant functions. Hybridizations of
      salt cress RNA targets to an Arabidopsis whole-genome oligonucleotide array
      indicate that commonly stress-associated transcripts are expressed at a
      noticeably higher level in unstressed salt cress plants and are induced rapidly
      under stress. Efficient transformation of salt cress allows for simple gene
      exchange between Arabidopsis and salt cress. In addition, the generation of T-DNA
      tagged mutant collections of salt cress, already in progress, will open the door
      to a new era of forward and reverse genetic studies of extremophile plant
      biology.

PMID- 15247370
TI  - The salt-stress signal transduction pathway that activates the gpx1 promoter is
      mediated by intracellular H2O2, different from the pathway induced by
      extracellular H2O2.
AB  - Several genes encoding putative glutathione peroxidase have been isolated from a
      variety of plants, all of which show the highest homology to the phospholipid
      hydroperoxide isoform. Several observations suggest that the proteins are
      involved in biotic and abiotic stress responses. Previous studies on the
      regulation of gpx1, the Citrus sinensis gene encoding phospholipid hydroperoxide
      isoform, led to the conclusion that salt-induced expression of gpx1 transcript
      and its encoded protein is mediated by oxidative stress. In this paper, we
      describe the induction of gpx1 promoter:uidA fusions in stable transformants of
      tobacco (Nicotiana tabacum) cultured cells and plants. We show that the induction
      of gpx1 by salt and oxidative stress occurs at the transcriptional level. gpx1
      promoter analysis confirmed our previous assumption that the salt signal is
      transduced via oxidative stress. We used induction of the fusion construct to
      achieve better insight into, and to monitor salt-induced oxidative stress. The
      gpx1 promoter responded preferentially to oxidative stress in the form of
      hydrogen peroxide, rather than to superoxide-generating agents. Antioxidants
      abolished the salt-induced expression of gpx1 promoter, but were unable to
      eliminate the induction by H2O2. The commonly employed NADPH-oxidase inhibitor
      diphenyleneiodonium chloride and catalase inhibited the H2O2-induced expression
      of gpx1 promoter, but did not affect its induction by salt. Our results led us to
      conclude that salt induces oxidative stress in the form of H2O2, its production
      occurs in the intracellular space, and its signal transduction pathway activating
      the gpx1 promoter is different from the pathway induced by extracellular H2O2.

PMID- 15247371
TI  - Characterization of a novel calcium/calmodulin-dependent protein kinase from
      tobacco.
AB  - A cDNA encoding a calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase (CaMK)
      from tobacco (Nicotiana tabacum), NtCaMK1, was isolated by protein-protein
      interaction-based screening of a cDNA expression library using 35S-labeled CaM as
      a probe. The genomic sequence is about 24.6 kb, with 21 exons, and the full
      length cDNA is 4.8 kb, with an open reading frame for NtCaMK1 consisting of 1,415
      amino acid residues. NtCaMK1 has all 11 subdomains of a kinase catalytic domain,
      lacks EF hands for Ca2+-binding, and is structurally similar to other CaMKs in
      mammal systems. Biochemical analyses have identified NtCaMK1 as a Ca2+/CaMK since
      NtCaMK1 phosphorylated itself and histone IIIs as substrate only in the presence
      of Ca2+/CaM with a Km of 44.5 microm and a Vmax of 416.2 nm min(-1) mg(-1).
      Kinetic analysis showed that the kinase not previously autophosphorylated had a
      Km for the synthetic peptide syntide-2 of 22.1 microm and a Vmax of 644.1 nm min(
      1) mg(-1) when assayed in the presence of Ca2+/CaM. Once the autophosphorylation
      of NtCaMK1 was initiated, the phosphorylated form displayed Ca2+/CaM-independent
      behavior, as many other CaMKs do. Analysis of the CaM-binding domain (CaMBD) in
      NtCaMK1 with truncated and site-directed mutated forms defined a stretch of 20
      amino acid residues at positions 913 to 932 as the CaMBD with high CaM affinity
      (Kd = 5 nm). This CaMBD was classified as a 1-8-14 motif. The activation of
      NtCaMK1 was differentially regulated by three tobacco CaM isoforms (NtCaM1,
      NtCaM3, and NtCaM13). While NtCaM1 and NtCaM13 activated NtCaMK1 effectively,
      NtCaM3 did not activate the kinase.

PMID- 15247372
TI  - Overexpression of OsRAA1 causes pleiotropic phenotypes in transgenic rice plants,
      including altered leaf, flower, and root development and root response to
      gravity.
AB  - There are very few root genes that have been described in rice as a
      monocotyledonous model plant so far. Here, the OsRAA1 (Oryza sativa Root
      Architecture Associated 1) gene has been characterized molecularly. OsRAA1
      encodes a 12.0-kD protein that has 58% homology to the AtFPF1 (Flowering
      Promoting Factor 1) in Arabidopsis, which has not been reported as modulating
      root development yet. Data of in situ hybridization and OsRAA1::GUS transgenic
      plant showed that OsRAA1 expressed specifically in the apical meristem, the
      elongation zone of root tip, steles of the branch zone, and the young lateral
      root. Constitutive expression of OsRAA1 under the control of maize (Zea mays)
      ubiquitin promoter resulted in phenotypes of reduced growth of primary root,
      increased number of adventitious roots and helix primary root, and delayed
      gravitropic response of roots in seedlings of rice (Oryza sativa), which are
      similar to the phenotypes of the wild-type plant treated with auxin. With
      overexpression of OsRAA1, initiation and growth of adventitious root were more
      sensitive to treatment of auxin than those of the control plants, while their
      responses to 9-hydroxyfluorene-9-carboxylic acid in both transgenic line and wild
      type showed similar results. OsRAA1 constitutive expression also caused longer
      leaves and sterile florets at the last stage of plant development. Analysis of
      northern blot and GUS activity staining of OsRAA1::GUS transgenic plants
      demonstrated that the OsRAA1 expression was induced by auxin. At the same time,
      overexpression of OsRAA1 also caused endogenous indole-3-acetic acid to increase.
      These data suggested that OsRAA1 as a new gene functions in the development of
      rice root systems, which are mediated by auxin. A positive feedback regulation
      mechanism of OsRAA1 to indole-3-acetic acid metabolism may be involved in rice
      root development in nature.

PMID- 15247373
TI  - Cytoskeletal proteins are coordinately increased in maize genotypes with high
      levels of eEF1A.
AB  - The opaque2 (o2) mutation increases the Lys content of maize (Zea mays) endosperm
      by reducing the synthesis of zein storage proteins and increasing the
      accumulation of other types of cellular proteins. Elongation factor 1A (eEF1A) is
      one of these proteins, and its concentration is highly correlated with the amount
      of other Lys-containing proteins in the endosperm. We investigated the basis for
      this relationship by comparing patterns of protein accumulation and gene
      expression between a high (Oh51Ao2) and a low (Oh545o2) eEF1A inbred, as well as
      between high and low eEF1A recombinant inbred lines obtained from their cross.
      The content of alpha-zein and several cytoskeletal proteins was measured in high
      and low eEF1A inbred lines, and the levels of these proteins were found to
      correlate with that of eEF1A. To extend this analysis, we used an endosperm
      expressed sequence tag microarray to examine steady-state levels of RNA
      transcripts in developing endosperm of these genotypes. We identified about 120
      genes coordinately regulated in association with eEF1A content. These genes
      encode proteins involved in several biological structures and processes,
      including the actin cytoskeleton, the endoplasmic reticulum, and the protein
      synthesis apparatus. Thus, higher levels of eEF1A in o2 mutants may be related to
      a more extensive cytoskeletal network surrounding the rough endoplasmic reticulum
      and increased synthesis of cytoskeleton-associated proteins, all of which
      contribute significantly to the Lys content of the endosperm.

PMID- 15247374
TI  - Evolution and function of the sucrose-phosphate synthase gene families in wheat
      and other grasses.
AB  - Suc-phosphate synthase (SPS) is a key regulatory enzyme in the pathway of Suc
      biosynthesis and has been linked to quantitative trait loci controlling plant
      growth and yield. In dicotyledonous plants there are three SPS gene families: A,
      B, and C. Here we report the finding of five families of SPS genes in wheat
      (Triticum aestivum) and other monocotyledonous plants from the family Poaceae
      (grasses). Three of these form separate subfamilies within the previously
      described A, B, and C gene families, but the other two form a novel and
      distinctive D family, which on present evidence is only found in the Poaceae. The
      D-type SPS proteins lack the phosphorylation sites associated with 14-3-3 protein
      binding and osmotic stress activation, and the linker region between the N
      terminal catalytic glucosyltransferase domain and the C-terminal Suc-phosphatase
      like domain is 80 to 90 amino acid residues shorter than in the A, B, or C types.
      The D family appears to have arisen after the divergence of mono- and
      dicotyledonous plants, with a later duplication event resulting in the two D-type
      subfamilies. Each of the SPS gene families in wheat showed different, but
      overlapping, spatial and temporal expression patterns, and in most organs at
      least two different SPS genes are expressed. Analysis of expressed sequence tags
      indicated similar expression patterns to wheat for each SPS gene family in barley
      (Hordeum vulgare) but not in more distantly related grasses. We identified an
      expressed sequence tag from rice (Oryza sativa) that appears to be derived from
      an endogenous antisense SPS gene, and this might account for the apparently low
      level of expression of the related OsSPS11 sense gene, adding to the already
      extensive list of mechanisms for regulating the activity of SPS in plants.

PMID- 15247375
TI  - Oxidative stress-induced calcium signaling in Arabidopsis.
AB  - Many environmental stresses result in increased generation of active oxygen
      species in plant cells. This leads to the induction of protective mechanisms,
      including changes in gene expression, which lead to antioxidant activity, the
      recovery of redox balance, and recovery from damage/toxicity. Relatively little
      is known about the signaling events that link perception of increased active
      oxygen species levels to gene expression in plants. We have investigated the role
      of calcium signaling in H2O2-induced expression of the GLUTATHIONE-S-TRANSFERASE1
      (GST1) gene. Challenge with H2O2 triggered a biphasic Ca2+ elevation in
      Arabidopsis seedlings. The early Ca2+ peak localized to the cotyledons, whereas
      the late Ca2+ rise was restricted to the root. The two phases of the Ca2+
      response were independent of each other, as shown by severing shoot from root
      tissues before H2O2 challenge. Modulation of the height of Ca2+ rises had a
      corresponding effect upon H2O2-induced GST1 expression. Application of the
      calcium channel blocker lanthanum reduced the height of the first Ca2+ peak and
      concomitantly inhibited GST1 expression. Conversely, enhancing the height of the
      H2O2-triggered Ca2+ signature by treatment with L-buthionine-[S,R]-sulfoximine
      (an inhibitor of glutathione synthesis) lead to enhancement of GST1 induction.
      This finding also indicates that changes in the cellular redox balance constitute
      an early event in H2O2 signal transduction as reduction of the cellular redox
      buffer and thus the cell's ability to maintain a high GSH/GSSG ratio potentiated
      the plant's antioxidant response.

PMID- 15247376
TI  - Phototropins mediate blue and red light-induced chloroplast movements in
      Physcomitrella patens.
AB  - Phototropin is the blue-light receptor that mediates phototropism, chloroplast
      movement, and stomatal opening in Arabidopsis. Blue and red light induce
      chloroplast movement in the moss Physcomitrella patens. To study the
      photoreceptors for chloroplast movement in P. patens, four phototropin genes
      (PHOTA1, PHOTA2, PHOTB1, and PHOTB2) were isolated by screening cDNA libraries.
      These genes were classified into two groups (PHOTA and PHOTB) on the basis of
      their deduced amino acid sequences. Then phototropin disruptants were generated
      by homologous recombination and used for analysis of chloroplast movement. Data
      revealed that blue light-induced chloroplast movement was mediated by
      phototropins in P. patens. Both photA and photB groups were able to mediate
      chloroplast avoidance, as has been reported for Arabidopsis phot2, although the
      photA group contributed more to the response. Red light-induced chloroplast
      movement was also significantly reduced in photA2photB1photB2 triple disruptants.
      Because the primary photoreceptor for red light-induced chloroplast movement in
      P. patens is phytochrome, phototropins may be downstream components of
      phytochromes in the signaling pathway. To our knowledge, this work is the first
      to show a function for the phototropin blue-light receptor in a response to
      wavelengths that it does not absorb.

PMID- 15247377
TI  - Critical roles of bacterioferritins in iron storage and proliferation of
      cyanobacteria.
AB  - Cyanobacteria are key contributors to global photosynthetic productivity, and
      iron availability is essential for cyanobacterial proliferation. While iron is
      abundant in the earth's crust, its unique chemical properties render it a
      limiting factor for photoautotrophic growth. As compared to other
      nonphotosynthetic organisms, oxygenic photosynthetic organisms such as
      cyanobacteria, algae, and green plants need large amounts of iron to maintain
      functional PSI complexes in their photosynthetic apparatus. Ferritins and
      bacterioferritins are ubiquitously present iron-storage proteins. We have found
      that in the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803),
      bacterioferritins are responsible for the storage of as much as 50% of cellular
      iron. Synechocystis 6803, as well as many other cyanobacterial species, have two
      bacterioferritins, BfrA and BfrB, in which either the heme binding or di-iron
      center ligating residues are absent. Purified bacterioferritin complex from
      Synechocystis 6803 has both BfrA and BfrB proteins. Targeted mutagenesis of each
      of the two bacterioferritin genes resulted in poor growth under iron-deprived
      conditions. Inactivation of both genes did not result in a more severe phenotype.
      These results support the presence of a heteromultimeric structure of
      Synechocystis bacterioferritin, in which one subunit ligates a di-iron center
      while the other accommodates heme binding. Notably, the reduced internal iron
      concentrations in the mutant cells resulted in a lower content of PSI. In
      addition, they triggered iron starvation responses even in the presence of normal
      levels of external iron, thus demonstrating a central role of bacterioferritins
      in iron homeostasis in these photosynthetic organisms.

PMID- 15247378
TI  - Targeted modification of homogalacturonan by transgenic expression of a fungal
      polygalacturonase alters plant growth.
AB  - Pectins are a highly complex family of cell wall polysaccharides comprised of
      homogalacturonan (HGA), rhamnogalacturonan I and rhamnogalacturonan II. We have
      specifically modified HGA in both tobacco (Nicotiana tabacum) and Arabidopsis by
      expressing the endopolygalacturonase II of Aspergillus niger (AnPGII). Cell walls
      of transgenic tobacco plants showed a 25% reduction in GalUA content as compared
      with the wild type and a reduced content of deesterified HGA as detected by
      antibody labeling. Neutral sugars remained unchanged apart from a slight increase
      of Rha, Ara, and Gal. Both transgenic tobacco and Arabidopsis were dwarfed,
      indicating that unesterified HGA is a critical factor for plant cell growth. The
      dwarf phenotypes were associated with AnPGII activity as demonstrated by the
      observation that the mutant phenotype of tobacco was completely reverted by
      crossing the dwarfed plants with plants expressing PGIP2, a strong inhibitor of
      AnPGII. The mutant phenotype in Arabidopsis did not appear when transformation
      was performed with a gene encoding AnPGII inactivated by site directed
      mutagenesis.

PMID- 15247379
TI  - Role of Hsp17.4-CII as coregulator and cytoplasmic retention factor of tomato
      heat stress transcription factor HsfA2.
AB  - HsfA2 is a heat stress (hs)-induced Hsf in peruvian tomato (Lycopersicon
      peruvianum) and the cultivated form Lycopersicon esculentum. Due to the high
      activator potential and the continued accumulation during repeated cycles of heat
      stress and recovery, HsfA2 becomes a dominant Hsf in thermotolerant cells. The
      formation of heterooligomeric complexes with HsfA1 leads to nuclear retention and
      enhanced transcriptional activity of HsfA2. This effect seems to represent one
      part of potential molecular mechanisms involved in its activity control. As shown
      in this paper, the activity of HsfA2 is also controlled by a network of
      nucleocytoplasmic small Hsps influencing its solubility, intracellular
      localization and activator function. By yeast two-hybrid interaction and
      transient coexpression studies in tobacco (Nicotiana plumbaginifolia) mesophyll
      protoplasts, we found that tomato (Lycopersicon esculentum) Hsp17.4-CII acts as
      corepressor of HsfA2. Given appropriate conditions, both proteins together formed
      large cytosolic aggregates which could be solubilized in presence of class CI
      sHsps. However, independent of the formation of aggregates or of the
      nucleocytoplasmic distribution of HsfA2, its transcriptional activity was
      specifically repressed by interaction of Hsp17.4-CII with the C-terminal
      activator domain. Although not identical in all aspects, the situation with the
      highly expressed, heat stress-inducible Arabidopsis HsfA2 was found to be
      principally similar. In corresponding reporter assays its activity was repressed
      in presence of AtHsp17.7-CII but not of AtHsp17.6-CII or LpHsp17.4-CII.

PMID- 15247380
TI  - Long term transcript accumulation during the development of dehydration
      adaptation in Cicer arietinum.
AB  - Cool season crops face intermittent drought. Exposure to drought and other
      abiotic stresses is known to increase tolerance of the plants against subsequent
      exposure to such stresses. Storage of environmental signals is also proposed.
      Preexposure to a dehydration shock improved adaptive response during subsequent
      dehydration treatment in a cool season crop chickpea (Cicer arietinum). We have
      identified 101 dehydration-inducible transcripts of chickpea by repetitive rounds
      of cDNA subtraction; differential DNA-array hybridization followed by northern
      blot analysis and analyzed their responses to exogenous application of abscisic
      acid (ABA). Steady-state expression levels of the dehydration-induced transcripts
      were monitored during the recovery period between 2 consecutive dehydration
      stresses. Seven of them maintained more than 3-fold of expression after 24 h and
      more than 2-fold of expression level even at 72 h after the removal of stress.
      Noticeably, all of them were inducible by exogenous ABA treatment. When the
      seedlings were subjected to recover similarly after an exposure to exogenous ABA,
      the steady-state abundances of 6 of them followed totally different kinetics
      returning to basal level expression within 24 h. This observation indicated a
      correlation between the longer period of abundance of those transcripts in the
      recovery period and improved adaptation of the plants to subsequent dehydration
      stress and suggested that both ABA-dependent and -independent mechanisms are
      involved in the maintenance of the messages from the previous stress experience.

PMID- 15247381
TI  - Transcriptional programs of early reproductive stages in Arabidopsis.
AB  - The life cycle of flowering plants alternates between a diploid sporophytic and a
      haploid gametophytic generation. After fertilization of each the egg and central
      cells by one male gamete, the development of both fertilization products occurs
      coordinated with the maternally derived seed coat and carpel tissues forming the
      fruit. The reproduction program is likely to involve the concerted activity of
      many genes. To identify genes with specific functions during reproduction, we
      have analyzed the expression profile of more than 22,000 genes present on the
      Arabidopsis ATH1 microarray during three stages of flower and fruit development.
      We found 1,886 genes regulated during reproductive development and 1,043 genes
      that were specifically expressed during reproduction. When compared to cells from
      an Arabidopsis suspension culture, S-phase genes were underrepresented and G2 and
      M-phase genes were strongly enriched in the set of specific genes, indicating
      that important functions during reproduction are exerted in the G2 and M phases
      of the cell cycle. Many potential signaling components, such as receptor-like
      protein kinases, phosphatases, and transcription factors, were present in both
      groups of genes. Members of the YABBY, MADS box, and Myb transcription factor
      families were significantly overrepresented in the group of specific genes,
      revealing an important role of these families during reproduction. Furthermore,
      we found a significant enrichment of predicted secreted proteins smaller than 15
      kD that could function directly as signaling molecules or as precursors for
      peptide hormones. Our study provides a basis for targeted reverse-genetic
      approaches aimed to identify key genes of reproductive development in plants.

PMID- 15247382
TI  - Abscisic acid induces CBF gene transcription and subsequent induction of cold
      regulated genes via the CRT promoter element.
AB  - Many cold-regulated genes of Arabidopsis are inducible by abscisic acid (ABA) as
      well as by cold. This has been thought to occur via two separate signaling
      pathways, with ABA acting via ABA-responsive promoter elements and low
      temperature activating the C-repeat element (CRT; dehydration-responsive)
      promoter element via CBF (DREB1) transcription factors. We show here that ABA is
      also capable of activating the CRT promoter element. Although the more recently
      discovered ABA-inducible CBF4 transcription factor might have accounted for this,
      we show here that CBF1-3 transcript levels also increase in response to elevated
      ABA levels. This increase in CBF1-3 transcript levels appears to be at least in
      part due to increased activity of the CBF promoters in response to ABA. A total
      of 125 bp of the CBF2 promoter, which has previously been shown to be sufficient
      for cold-, mechanical-, and cycloheximide-induced expression, was also sufficient
      for ABA-induced expression. However, the ABA-responsive promoter element-like
      motif within this region is not needed for ABA-induced expression. An observed
      increase in CBF protein levels after ABA treatment, together with previous data
      showing that increased CBF levels are sufficient for cold-regulated gene
      induction, suggests that ABA-induced increases in CBF1-3 transcript levels do
      have the potential to activate the CRT. Our data indicate therefore that
      activation of the CRT may also occur via a novel ABA-inducible signaling pathway
      using the normally cold-inducible CBFs.

PMID- 15247383
TI  - Novel biosynthetic pathway of castasterone from cholesterol in tomato.
AB  - Endogenous brassinosteroids (BRs) in tomato (Lycopersicon esculentum) seedlings
      are known to be composed of C27- and C28-BRs. The biosynthetic pathways of C27
      BRs were examined using a cell-free enzyme solution prepared from tomato
      seedlings that yielded the biosynthetic sequences cholesterol --> cholestanol and
      6-deoxo-28-norteasterone <--> 6-deoxo-28-nor-3-dehydroteasterone <--> 6-deoxo-28
      nortyphasterol --> 6-deoxo-28-norcastasterone --> 28-norcastasterone (28-norCS).
      Arabidopsis CYP85A1 that was heterologously expressed in yeast mediated the
      conversion of 6-deoxo-28-norCS to 28-norCS. The same reaction was catalyzed by an
      enzyme solution from wild-type tomato but not by an extract derived from a tomato
      dwarf mutant with a defect in CYP85. Furthermore, exogenously applied 28-norCS
      restored the abnormal growth of the dwarf mutant. These findings indicate that
      the C-6 oxidation of 6-deoxo-28-norCS to 28-norCS in tomato seedlings is
      catalyzed by CYP85, just as in the conversion of 6-deoxoCS to CS. Additionally,
      the cell-free solution also catalyzed the C-24 methylation of 28-norCS to CS in
      the presence of NADPH and S-adenosylmethionine (SAM), a reaction that was clearly
      retarded in the absence of NADPH and SAM. Thus it seems that C27-BRs, in addition
      to C28-BRs, are important in the production of more active C28-BRs and CS, where
      a SAM-dependent sterol methyltransferase appears to biosynthetically connect C27
      BRs to C28-BRs. Moreover, the tomato cell-free solution converted CS to 26-norCS
      and [2H6]CS to [2H3]28-norCS, suggesting that C-28 demethylation is an artifact
      due to an isotope effect. Although previous feeding experiments employing [2H6]CS
      suggested that 28-norCS was synthesized from CS in certain plant species, this is
      not supported in planta. Altogether, this study demonstrated for the first time,
      to our knowledge, that 28-norCS is not synthesized from CS but from cholesterol.
      In addition, CS and [2H6]CS were not converted into BL and [2H6]BL, respectively,
      confirming an earlier finding that the active BR in tomato seedlings is not BL
      but CS. In conclusion, the biosynthesis of 28-norBRs appears to play a
      physiologically important role in maintaining homeostatic levels of CS in tomato
      seedlings.

PMID- 15247384
TI  - Loss of highly branched arabinans and debranching of rhamnogalacturonan I
      accompany loss of firm texture and cell separation during prolonged storage of
      apple.
AB  - Growth and maturation of the edible cortical cells of apples (Malus domestica
      Borkh) are accompanied by a selective loss of pectin-associated (1-->4)-beta-D
      galactan from the cell walls, whereas a selective loss of highly branched (1-->5)
      alpha-L-arabinans occurs after ripening and in advance of the loss of firm
      texture. The selective loss of highly branched arabinans occurs during the
      overripening of apples of four cultivars (Gala, Red Delicious, Firm Gold, and
      Gold Rush) that varied markedly in storage life, but, in all instances, the loss
      prestages the loss of firm texture, measured by both breaking strength and
      compression resistance. The unbranched (1-->5)-linked arabinans remain associated
      with the major pectic polymer, rhamnogalacturonan I, and their content remains
      essentially unchanged during overripening. However, the degree of
      rhamnogalacturonan I branching at the rhamnosyl residues also decreases, but only
      after extensive loss of the highly branched arabinans. In contrast to the
      decrease in arabinan content, the loss of the rhamnogalacturonan I branching is
      tightly correlated with loss of firm texture in all cultivars, regardless of
      storage time. In vitro cell separation assays show that structural proteins,
      perhaps via their phenolic residues, and homogalacturonans also contribute to
      cell adhesion. Implications of these cell wall modifications in the mechanisms of
      apple cortex textural changes and cell separation are discussed.

PMID- 15247385
TI  - The biosynthesis of D-Galacturonate in plants. functional cloning and
      characterization of a membrane-anchored UDP-D-Glucuronate 4-epimerase from
      Arabidopsis.
AB  - Pectic cell wall polysaccharides owe their high negative charge to the presence
      of D-galacturonate, a monosaccharide that appears to be present only in plants
      and some prokaryotes. UDP-D-galacturonate, the activated form of this sugar, is
      known to be formed by the 4-epimerization of UDP-D-glucuronate; however, no
      coding regions for the epimerase catalyzing this reaction have previously been
      described in plants. To better understand the mechanisms by which precursors for
      pectin synthesis are produced, we used a bioinformatics approach to identify and
      functionally express a UDP-D-glucuronate 4-epimerase (GAE1) from Arabidopsis.
      GAE1 is predicted to be a type II membrane protein that belongs to the family of
      short-chain dehydrogenases/reductases. The recombinant enzyme expressed in Pichia
      pastoris established a 1.3:1 equilibrium between UDP-D-galacturonate and UDP-D
      glucuronate but did not epimerize UDP-D-Glc or UDP-D-Xyl. Enzyme assays on cell
      extracts localized total UDP-D-glucuronate 4-epimerase and recombinant GAE1
      activity exclusively to the microsomal fractions of Arabidopsis and Pichia,
      respectively. GAE1 had a pH optimum of 7.6 and an apparent Km of 0.19 mm. The
      recombinant enzyme was strongly inhibited by UDP-D-Xyl but not by UDP, UDP-D-Glc,
      or UDP-D-Gal. Analysis of Arabidopsis plants transformed with a GAE1:GUS
      construct showed expression in all tissues. The Arabidopsis genome contains five
      GAE1 paralogs, all of which are transcribed and predicted to contain a membrane
      anchor. This suggests that all of these enzymes are targeted to an endomembrane
      system such as the Golgi where they may provide UDP-D-galacturonate to
      glycosyltransferases in pectin synthesis.

PMID- 15247386
TI  - RNAi-mediated tocopherol deficiency impairs photoassimilate export in transgenic
      potato plants.
AB  - Tocopherols (vitamin E) are lipophilic antioxidants presumed to play a key role
      in protecting chloroplast membranes and the photosynthetic apparatus from
      photooxidative damage. Additional nonantioxidant functions of tocopherols have
      been proposed after the recent finding that the Suc export defective1 maize (Zea
      mays) mutant (sxd1) carries a defect in tocopherol cyclase (TC) and thus is
      devoid of tocopherols. However, the corresponding vitamin E deficient1
      Arabidopsis mutant (vte1) lacks a phenotype analogous to sxd1, suggesting
      differences in tocopherol function between C4 and C3 plants. Therefore, in this
      study, the potato (Solanum tuberosum) ortholog of SXD1 was isolated and
      functionally characterized. StSXD1 encoded a protein with high TC activity in
      vitro, and chloroplastic localization was demonstrated by transient expression of
      green fluorescent protein-tagged fusion constructs. RNAi-mediated silencing of
      StSXD1 in transgenic potato plants resulted in the disruption of TC activity and
      severe tocopherol deficiency similar to the orthologous sxd1 and vte1 mutants.
      The nearly complete absence of tocopherols caused a characteristic
      photoassimilate export-defective phenotype comparable to sxd1, which appeared to
      be a consequence of vascular-specific callose deposition observed in source
      leaves. CO2 assimilation rates and photosynthetic gene expression were decreased
      in source leaves in close correlation with excess sugar accumulation, suggesting
      a carbohydrate-mediated feedback inhibition rather than a direct impact of
      tocopherol deficiency on photosynthetic capacity. This conclusion is further
      supported by an increased photosynthetic capacity of young leaves regardless of
      decreased tocopherol levels. Our data provide evidence that tocopherol deficiency
      leads to impaired photoassimilate export from source leaves in both monocot and
      dicot plant species and suggest significant differences among C3 plants in
      response to tocopherol reduction.

PMID- 15247387
TI  - Cloning and functional characterization of a phospholipid:diacylglycerol
      acyltransferase from Arabidopsis.
AB  - A new pathway for triacylglycerol biosynthesis involving a
      phospholipid:diacylglycerol acyltransferase (PDAT) was recently described
      (Dahlqvist A, Stahl U, Lenman M, Banas A, Lee M, Sandager L, Ronne H, Stymne S,
      [2000] Proc Natl Acad Sci USA 97: 6487-6492). The LRO1 gene that encodes the PDAT
      was identified in yeast (Saccharomyces cerevisiae) and shown to have homology
      with animal lecithin:cholesterol acyltransferase. A search of the Arabidopsis
      genome database identified the protein encoded by the At5g13640 gene as the
      closest homolog to the yeast PDAT (28% amino acid identity). The cDNA of
      At5g13640 (AtPDAT gene) was overexpressed in Arabidopsis behind the cauliflower
      mosaic virus promoter. Microsomal preparations of roots and leaves from
      overexpressers had PDAT activities that correlated with expression levels of the
      gene, thus demonstrating that this gene encoded PDAT (AtPDAT). The AtPDAT
      utilized different phospholipids as acyl donor and accepted acyl groups ranging
      from C10 to C22. The rate of activity was highly dependent on acyl composition
      with highest activities for acyl groups containing several double bonds, epoxy,
      or hydroxy groups. The enzyme utilized both sn-positions of phosphatidylcholine
      but had a 3-fold preference for the sn-2 position. The fatty acid and lipid
      composition as well as the amounts of lipids per fresh weight in Arabidopsis
      plants overexpressing AtPDAT were not significantly different from the wild type.
      Microsomal preparations of roots from a T-DNA insertion mutant in the AtPDAT gene
      had barely detectable capacity to transfer acyl groups from phospholipids to
      added diacylglycerols. However, these microsomes were still able to carry out
      triacylglycerol synthesis by a diacylglycerol:diacylglycerol acyltransferase
      reaction at the same rate as microsomal preparations from wild type.

PMID- 15247388
TI  - A plant-specific subclass of C-terminal kinesins contains a conserved a-type
      cyclin-dependent kinase site implicated in folding and dimerization.
AB  - Cyclin-dependent kinases (CDKs) control cell cycle progression through timely
      coordinated phosphorylation events. Two kinesin-like proteins that interact with
      CDKA;1 were identified and designated KCA1 and KCA2. They are 81% identical and
      have a similar three-partite domain organization. The N-terminal domain contains
      an ATP and microtubule-binding site typical for kinesin motors. A green
      fluorescent protein (GFP) fusion of the N-terminal domain of KCA1 decorated
      microtubules in Bright Yellow-2 cells, demonstrating microtubule-binding
      activity. During cytokinesis the full-length GFP-fusion protein accumulated at
      the midline of young and mature expanding phragmoplasts. Two-hybrid analysis and
      coimmunoprecipitation experiments showed that coiled-coil structures of the
      central stalk were responsible for homo- and heterodimerization of KCA1 and KCA2.
      By western-blot analysis, high molecular mass KCA molecules were detected in
      extracts from Bright Yellow-2 cells overproducing the full-length GFP fusion.
      Treatment of these cultures with the phosphatase inhibitor vanadate caused an
      accumulation of these KCA molecules. In addition to dimerization, interactions
      within the C-terminally located tail domain were revealed, indicating that the
      tail could fold onto itself. The tail domains of KCA1 and KCA2 contained two
      adjacent putative CDKA;1 phosphorylation sites, one of which is conserved in KCA
      homologs from other plant species. Site-directed mutagenesis of the conserved
      phosphorylation sites in KCA1 resulted in a reduced binding with CDKA;1 and
      abolished intramolecular tail interactions. The data show that phosphorylation of
      the CDKA;1 site provokes a conformational change in the structure of KCA with
      implications in folding and dimerization.

PMID- 15247389
TI  - Spermidine synthase genes are essential for survival of Arabidopsis.
AB  - The cellular polyamines putrescine, spermidine, and spermine are ubiquitous in
      nature and have been implicated in a wide range of growth and developmental
      processes. There is little information, however, on mutant plants or animals
      defective in the synthesis of polyamines. The Arabidopsis genome has two genes
      encoding spermidine synthase, SPDS1 and SPDS2. In this paper, we describe T-DNA
      insertion mutants of both of these genes. While each mutant allele shows normal
      growth, spds1-1 spds2-1 double-mutant seeds are abnormally shrunken and they have
      embryos that are arrested morphologically at the heart-torpedo transition stage.
      These seeds contain significantly reduced levels of spermidine and high levels of
      its precursor, putrescine. The embryo lethal phenotype of spds1-1 spds2-1 is
      complemented by the wild-type SPDS1 gene. In addition, we observed a nearly
      identical seed phenotype among an F2 seed population from the cross between the
      spds2-1 allele and SPDS1 RNA interference transgenic lines. These data provide
      the first genetic evidence indicating a critical role of the spermidine synthase
      in plant embryo development.

PMID- 15247390
TI  - The effect of water, sugars, and proteins on the pattern of ice nucleation and
      propagation in acclimated and nonacclimated canola leaves.
AB  - Infrared video thermography was used to observe ice nucleation temperatures,
      patterns of ice formation, and freezing rates in nonacclimated and cold
      acclimated leaves of a spring (cv Quest) and a winter (cv Express) canola
      (Brassica napus). Distinctly different freezing patterns were observed, and the
      effect of water content, sugars, and soluble proteins on the freezing process was
      characterized. When freezing was initiated at a warm subzero temperature, ice
      growth rapidly spread throughout nonacclimated leaves. In contrast, acclimated
      leaves initiated freezing in a horseshoe pattern beginning at the uppermost edge
      followed by a slow progression of ice formation across the leaf. However, when
      acclimated leaves, either previously killed by a slow freeze (2 degrees C h(-1))
      or by direct submersion in liquid nitrogen, were refrozen their freezing pattern
      was similar to nonacclimated leaves. A novel technique was developed using filter
      paper strips to determine the effects of both sugars and proteins on the rate of
      freezing of cell extracts. Cell sap from nonacclimated leaves froze 3-fold faster
      than extracts from acclimated leaves. The rate of freezing in leaves was strongly
      dependent upon the osmotic potential of the leaves. Simple sugars had a much
      greater effect on freezing rate than proteins. Nonacclimated leaves containing
      high water content did not supercool as much as acclimated leaves. Additionally,
      wetted leaves did not supercool as much as nonwetted leaves. As expected, cell
      solutes depressed the nucleation temperature of leaves. The use of infrared
      thermography has revealed that the freezing process in plants is a complex
      process, reminding us that many aspects of freezing tolerance occur at a whole
      plant level involving aspects of plant structure and metabolites rather than just
      the expression of specific genes alone.

PMID- 15247391
TI  - Novel expression pattern of cytosolic Gln synthetase in nitrogen-fixing root
      nodules of the actinorhizal host, Datisca glomerata.
AB  - Gln synthetase (GS) is the key enzyme of primary ammonia assimilation in nitrogen
      fixing root nodules of legumes and actinorhizal (Frankia-nodulated) plants. In
      root nodules of Datisca glomerata (Datiscaceae), transcripts hybridizing to a
      conserved coding region of the abundant nodule isoform, DgGS1-1, are abundant in
      uninfected nodule cortical tissue, but expression was not detectable in the
      infected zone or in the nodule meristem. Similarly, the GS holoprotein is
      immunolocalized exclusively to the uninfected nodule tissue. Phylogenetic
      analysis of the full-length cDNA of DgGS1-1 indicates affinities with cytosolic
      GS genes from legumes, the actinorhizal species Alnus glutinosa, and
      nonnodulating species, Vitis vinifera and Hevea brasilensis. The D. glomerata
      nodule GS expression pattern is a new variant among reported root nodule
      symbioses and may reflect an unusual nitrogen transfer pathway from the Frankia
      nodule microsymbiont to the plant infected tissue, coupled to a distinctive
      nitrogen cycle in the uninfected cortical tissue. Arg, Gln, and Glu are the major
      amino acids present in D. glomerata nodules, but Arg was not detected at high
      levels in leaves or roots. Arg as a major nodule nitrogen storage form is not
      found in other root nodule types except in the phylogenetically related Coriaria.
      Catabolism of Arg through the urea cycle could generate free ammonium in the
      uninfected tissue where GS is expressed.

PMID- 15247392
TI  - Microarray analyses of gene expression during adventitious root development in
      Pinus contorta.
AB  - In order to investigate the gene expression pattern during adventitious root
      development, RNA of Pinus contorta hypocotyls, pulse-treated with the auxin
      indole-3-butyric acid and harvested at distinct developmental time points of root
      development, was hybridized to microarrays containing 2,178 cDNAs from Pinus
      taeda. Over the period of observation of root development, the transcript levels
      of 220 genes changed significantly. During the root initiation phase, genes
      involved in cell replication and cell wall weakening and a transcript encoding a
      PINHEAD/ZWILLE-like protein were up-regulated, while genes related to auxin
      transport, photosynthesis, and cell wall synthesis were down-regulated. In
      addition, there were changes in transcript abundance of genes related to water
      stress. During the root meristem formation phase the transcript abundances of
      genes involved in auxin transport, auxin responsive transcription, and cell wall
      synthesis, and of a gene encoding a B-box zinc finger-like protein, increased,
      while those encoding proteins involved in cell wall weakening decreased. Changes
      of transcript abundance of genes related to water stress during the root meristem
      formation and root formation phase indicate that the plant roots had become
      functional in water transport. Simultaneously, genes involved in auxin transport
      were up-regulated, while genes related to cell wall modification were down
      regulated. Finally, during the root elongation phase down-regulation of
      transcripts encoding proteins involved in cell replication and stress occurred.
      Based on the observed changes in transcript abundances, we suggest hypotheses
      about the relative importance of various physiological processes during the auxin
      induced development of roots in P. contorta.

PMID- 15247393
TI  - Autophosphorylation and subcellular localization dynamics of a salt- and water
      deficit-induced calcium-dependent protein kinase from ice plant.
AB  - A salinity and dehydration stress-responsive calcium-dependent protein kinase
      (CDPK) was isolated from the common ice plant (Mesembryanthemum crystallinum;
      McCPK1). McCPK1 undergoes myristoylation, but not palmitoylation in vitro.
      Removal of the N-terminal myristate acceptor site partially reduced McCPK1 plasma
      membrane (PM) localization as determined by transient expression of green
      fluorescent protein fusions in microprojectile-bombarded cells. Removal of the N
      terminal domain (amino acids 1-70) completely abolished PM localization,
      suggesting that myristoylation and possibly the N-terminal domain contribute to
      membrane association of the kinase. The recombinant, Escherichia coli-expressed,
      full-length McCPK1 protein was catalytically active in a calcium-dependent manner
      (K0.5 = 0.15 microm). Autophosphorylation of recombinant McCPK1 was observed in
      vitro on at least two different Ser residues, with the location of two sites
      being mapped to Ser-62 and Ser-420. An Ala substitution at the Ser-62 or Ser-420
      autophosphorylation site resulted in a slight increase in kinase activity
      relative to wild-type McCPK1 against a histone H1 substrate. In contrast, Ala
      substitutions at both sites resulted in a dramatic decrease in kinase activity
      relative to wild-type McCPK1 using histone H1 as substrate. McCPK1 undergoes a
      reversible change in subcellular localization from the PM to the nucleus,
      endoplasmic reticulum, and actin microfilaments of the cytoskeleton in response
      to reductions in humidity, as determined by transient expression of McCPK1-green
      fluorescent protein fusions in microprojectile-bombarded cells and confirmed by
      subcellular fractionation and western-blot analysis of 6x His-tagged McCPK1.

PMID- 15247394
TI  - Phylogenetic analyses in cornus substantiate ancestry of xylem supercooling
      freezing behavior and reveal lineage of desiccation related proteins.
AB  - The response of woody plant tissues to freezing temperature has evolved into two
      distinct behaviors: an avoidance strategy, in which intracellular water
      supercools, and a freeze-tolerance strategy, where cells tolerate the loss of
      water to extracellular ice. Although both strategies involve extracellular ice
      formation, supercooling cells are thought to resist freeze-induced dehydration.
      Dehydrin proteins, which accumulate during cold acclimation in numerous
      herbaceous and woody plants, have been speculated to provide, among other things,
      protection from desiccative extracellular ice formation. Here we use Cornus as a
      model system to provide the first phylogenetic characterization of xylem freezing
      behavior and dehydrin-like proteins. Our data suggest that both freezing behavior
      and the accumulation of dehydrin-like proteins in Cornus are lineage related;
      supercooling and nonaccumulation of dehydrin-like proteins are ancestral within
      the genus. The nonsupercooling strategy evolved within the blue- or white-fruited
      subgroup where representative species exhibit high levels of freeze tolerance.
      Within the blue- or white-fruited lineage, a single origin of dehydrin-like
      proteins was documented and displayed a trend for size increase in molecular
      mass. Phylogenetic analyses revealed that an early divergent group of red-fruited
      supercooling dogwoods lack a similar protein. Dehydrin-like proteins were limited
      to neither nonsupercooling species nor to those that possess extreme freeze
      tolerance.

PMID- 15247395
TI  - The innate immunity of a marine red alga involves oxylipins from both the
      eicosanoid and octadecanoid pathways.
AB  - The oxygenated derivatives of fatty acids, known as oxylipins, are pivotal
      signaling molecules in animals and terrestrial plants. In animal systems,
      eicosanoids regulate cell differentiation, immune responses, and homeostasis. In
      contrast, terrestrial plants use derivatives of C18 and C16 fatty acids as
      developmental or defense hormones. Marine algae have emerged early in the
      evolution of eukaryotes as several distinct phyla, independent from the animal
      and green-plant lineages. The occurrence of oxylipins of the eicosanoid family is
      well documented in marine red algae, but their biological roles remain an enigma.
      Here we address the hypothesis that they are involved with the defense mechanisms
      of the red alga Chondrus crispus. By investigating its association with a green
      algal endophyte Acrochaete operculata, which becomes invasive in the diploid
      generation of this red alga, we showed that (1) when challenged by pathogen
      extracts, the resistant haploid phase of C. crispus produced both C20 and C18
      oxylipins, (2) elicitation with pathogen extracts or methyl jasmonate activated
      the metabolism of C20 and C18 polyunsaturated fatty acids to generate
      hydroperoxides and cyclopentenones such as prostaglandins and jasmonates, and (3)
      C20 and C18 hydroperoxides as well as methyl jasmonate did induce shikimate
      dehydrogenase and Phe ammonialyase activities in C. crispus and conferred an
      induced resistance to the diploid phase, while inhibitors of fatty acid oxidation
      reduced the natural resistance of the haploid generation. The dual nature of
      oxylipin metabolism in this alga suggests that early eukaryotes featured both
      animal- (eicosanoids) and plant-like (octadecanoids) oxylipins as essential
      components of innate immunity mechanisms.

PMID- 15247396
TI  - Green light stimulates early stem elongation, antagonizing light-mediated growth
      inhibition.
AB  - During the transition from darkness to light, the rate of hypocotyl elongation is
      determined from the integration of light signals sensed through the phototropin,
      cryptochrome, and phytochrome signaling pathways. In all light conditions
      studied, from UV to far-red, early hypocotyl growth is rapidly and robustly
      suppressed within minutes of illumination in a manner dependent upon light
      quality and quantity. In this study, it is shown that green light (GL)
      irradiation leads to a rapid increase in the growth rate of etiolated Arabidopsis
      seedlings. GL-mediated growth promotion was detected in response to constant
      irradiation or a short, single pulse of light with a similar time course. The
      response has a threshold between 10(-1) and 10(0) micromol m(-2), is saturated
      before 10(2) micromol m(-2) and obeys reciprocity. Genetic analyses indicate that
      the cryptochrome or phototropin photoreceptors do not participate in the
      response. The major phytochrome receptors influence the normal amplitude and
      timing of the GL response, yet the GL response is normal in seedlings grown for
      hours under constant dim-red light. Therefore, phytochrome activation enhances,
      but is not required for, the GL response. Seedlings grown under green, red, and
      blue light together are longer than those grown under red and blue alone. These
      data indicate that a novel GL-activated light sensor promotes early stem
      elongation that antagonizes growth inhibition.

PMID- 15247397
TI  - Expansins abundant in secondary xylem belong to subgroup A of the alpha-expansin
      gene family.
AB  - Differentiation of xylem cells in dicotyledonous plants involves expansion of the
      radial primary cell walls and intrusive tip growth of cambial derivative cells
      prior to the deposition of a thick secondary wall essential for xylem function.
      Expansins are cell wall-residing proteins that have an ability to plasticize the
      cellulose-hemicellulose network of primary walls. We found expansin activity in
      proteins extracted from the cambial region of mature stems in a model tree
      species hybrid aspen (Populus tremula x Populus tremuloides Michx). We identified
      three alpha-expansin genes (PttEXP1, PttEXP2, and PttEXP8) and one beta-expansin
      gene (PttEXPB1) in a cambial region expressed sequence tag library, among which
      PttEXP1 was most abundantly represented. Northern-blot analyses in aspen
      vegetative organs and tissues showed that PttEXP1 was specifically expressed in
      mature stems exhibiting secondary growth, where it was present in the cambium and
      in the radial expansion zone. By contrast, PttEXP2 was mostly expressed in
      developing leaves. In situ reverse transcription-PCR provided evidence for
      accumulation of mRNA of PttEXP1 along with ribosomal rRNA at the tips of
      intrusively growing xylem fibers, suggesting that PttEXP1 protein has a role in
      intrusive tip growth. An examination of tension wood and leaf cDNA libraries
      identified another expansin, PttEXP5, very similar to PttEXP1, as the major
      expansin in developing tension wood, while PttEXP3 was the major expansin
      expressed in developing leaves. Comparative analysis of expansins expressed in
      woody stems in aspen, Arabidopsis, and pine showed that the most abundantly
      expressed expansins share sequence similarities, belonging to the subfamily A of
      alpha-expansins and having two conserved motifs at the beginning and end of the
      mature protein, RIPVG and KNFRV, respectively. This conservation suggests that
      these genes may share a specialized, not yet identified function.

PMID- 15247398
TI  - A novel inhibitor of 9-cis-epoxycarotenoid dioxygenase in abscisic acid
      biosynthesis in higher plants.
AB  - Abscisic acid (ABA) is a major regulator in the adaptation of plants to
      environmental stresses, plant growth, and development. In higher plants, the ABA
      biosynthesis pathway involves the oxidative cleavage of 9-cis-epoxycarotenoids,
      which may be the key regulatory step in the pathway catalyzed by 9-cis
      epoxycarotenoid dioxygenase (NCED). We developed a new inhibitor of ABA
      biosynthesis targeting NCED and named it abamine (ABA biosynthesis inhibitor with
      an amine moiety). Abamine is a competitive inhibitor of NCED, with a Ki of 38.8
      microm. In 0.4 m mannitol solution, which mimics the effects of osmotic stress,
      abamine both inhibited stomatal closure in spinach (Spinacia oleracea) leaves,
      which was restored by coapplication of ABA, and increased luminescence intensity
      in transgenic Arabidopsis containing the RD29B promoter-luciferase fusion. The
      ABA content of plants in 0.4 m mannitol was increased approximately 16-fold as
      compared with that of controls, whereas 50 to 100 microm abamine inhibited about
      50% of this ABA accumulation in both spinach leaves and Arabidopsis. Abamine
      treated Arabidopsis was more sensitive to drought stress and showed a significant
      decrease in drought tolerance than untreated Arabidopsis. These results suggest
      that abamine is a novel ABA biosynthesis inhibitor that targets the enzyme
      catalyzing oxidative cleavage of 9-cis-epoxycarotenoids. To test the effect of
      abamine on plants other than Arabidopsis, it was applied to cress (Lepidium
      sativum) plants. Abamine enhanced radicle elongation in cress seeds, which could
      be due to a decrease in the ABA content of abamine-treated plants. Thus, it is
      possible to think that abamine should enable us to elucidate the functions of ABA
      in cells or plants and to find new mutants involved in ABA signaling.

PMID- 15247399
TI  - Contrasting modes of diversification in the Aux/IAA and ARF gene families.
AB  - The complete genomic sequence for Arabidopsis provides the opportunity to combine
      phylogenetic and genomic approaches to study the evolution of gene families in
      plants. The Aux/IAA and ARF gene families, consisting of 29 and 23 loci in
      Arabidopsis, respectively, encode proteins that interact to mediate auxin
      responses and regulate various aspects of plant morphological development. We
      developed scenarios for the genomic proliferation of the Aux/IAA and ARF families
      by combining phylogenetic analysis with information on the relationship between
      each locus and the previously identified duplicated genomic segments in
      Arabidopsis. This analysis shows that both gene families date back at least to
      the origin of land plants and that the major Aux/IAA and ARF lineages originated
      before the monocot-eudicot divergence. We found that the extant Aux/IAA loci
      arose primarily through segmental duplication events, in sharp contrast to the
      ARF family and to the general pattern of gene family proliferation in
      Arabidopsis. Possible explanations for the unusual mode of Aux/IAA duplication
      include evolutionary constraints imposed by complex interactions among proteins
      and pathways, or the presence of long-distance cis-regulatory sequences. The
      antiquity of the two gene families and the unusual mode of Aux/IAA
      diversification have a number of potential implications for understanding both
      the functional and evolutionary roles of these genes.

PMID- 15247400
TI  - Gene duplication in the carotenoid biosynthetic pathway preceded evolution of the
      grasses.
AB  - Despite ongoing research on carotenoid biosynthesis in model organisms, there is
      a paucity of information on pathway regulation operating in the grasses
      (Poaceae), which include plants of world-wide agronomic importance. As a result,
      efforts to either breed for or metabolically engineer improvements in carotenoid
      content or composition in cereal crops have led to unexpected results. In
      comparison to maize (Zea mays), rice (Oryza sativa) accumulates no endosperm
      carotenoids, despite having a functional pathway in chloroplasts. To better
      understand why these two related grasses differ in endosperm carotenoid content,
      we began to characterize genes encoding phytoene synthase (PSY), since this
      nuclear-encoded enzyme appeared to catalyze a rate-controlling step in the
      plastid-localized biosynthetic pathway. The enzyme had been previously associated
      with the maize Y1 locus thought to be the only functional gene controlling PSY
      accumulation, though function of the Y1 gene product had never been demonstrated.
      We show that both maize and rice possess and express products from duplicate PSY
      genes, PSY1 (Y1) and PSY2; PSY1 transcript accumulation correlates with
      carotenoid-containing endosperm. Using a heterologous bacterial system, we
      demonstrate enzyme function of PSY1 and PSY2 that are largely conserved in
      sequence except for N- and C-terminal domains. By database mining and use of
      ortholog-specific universal PCR primers, we found that the PSY duplication is
      prevalent in at least eight subfamilies of the Poaceae, suggesting that this
      duplication event preceded evolution of the Poaceae. These findings will impact
      study of grass phylogeny and breeding of enhanced carotenoid content in an entire
      taxonomic group of plant crops critical for global food security.

PMID- 15247401
TI  - AtOPT6 transports glutathione derivatives and is induced by primisulfuron.
AB  - The oligopeptide transporter (OPT) family contains nine members in Arabidopsis.
      While there is some evidence that AtOPTs mediate the uptake of tetra- and
      pentapeptides, OPT homologs in rice (Oryza sativa; OsGT1) and Indian mustard
      (Brassica juncea; BjGT1) have been described as transporters of glutathione
      derivatives. This study investigates the possibility that two members of the
      AtOPT family, AtOPT6 and AtOPT7, may also transport glutathione and its
      conjugates. Complementation of the hgt1met1 yeast double mutant by plant homologs
      of the yeast glutathione transporter HGT1 (AtOPT6, AtOPT7, OsGT1, BjGT1) did not
      restore the growth phenotype, unlike complementation by HGT1. By contrast,
      complementation by AtOPT6 restored growth of the hgt1 yeast mutant on a medium
      containing reduced (GSH) or oxidized glutathione as the sole sulfur source and
      induced uptake of [3H]GSH, whereas complementation by AtOPT7 did not. In these
      conditions, AtOPT6-dependent GSH uptake in yeast was mediated by a high affinity
      (Km = 400 microm) and a low affinity (Km = 5 mm) phase. It was strongly competed
      for by an excess oxidized glutathione and glutathione-N-ethylmaleimide conjugate.
      Growth assays of yeasts in the presence of cadmium (Cd) suggested that AtOPT6 may
      transport Cd and Cd/GSH conjugate. Reporter gene experiments showed that AtOPT6
      is mainly expressed in dividing areas of the plant (cambium, areas of lateral
      root initiation). RNA blots on cell suspensions and real-time reverse
      transcription-PCR on Arabidopsis plants indicated that AtOPT6 expression is
      strongly induced by primisulfuron and, to a lesser extent, by abscisic acid but
      not by Cd. Altogether, the data show that the substrate specificity and the
      physiological functions of AtOPT members may be diverse. In addition to peptide
      transport, AtOPT6 is able to transport glutathione derivatives and metal
      complexes, and may be involved in stress resistance.

PMID- 15247402
TI  - Comparative genomics in salt tolerance between Arabidopsis and aRabidopsis
      related halophyte salt cress using Arabidopsis microarray.
AB  - Salt cress (Thellungiella halophila), a halophyte, is a genetic model system with
      a small plant size, short life cycle, copious seed production, small genome size,
      and an efficient transformation. Its genes have a high sequence identity (90%-95%
      at cDNA level) to genes of its close relative, Arabidopsis. These qualities are
      advantageous not only in genetics but also in genomics, such as gene expression
      profiling using Arabidopsis cDNA microarrays. Although salt cress plants are salt
      tolerant and can grow in 500 mm NaCl medium, they do not have salt glands or
      other morphological alterations either before or after salt adaptation. This
      suggests that the salt tolerance in salt cress results from mechanisms that are
      similar to those operating in glycophytes. To elucidate the differences in the
      regulation of salt tolerance between salt cress and Arabidopsis, we analyzed the
      gene expression profiles in salt cress by using a full-length Arabidopsis cDNA
      microarray. In salt cress, only a few genes were induced by 250 mm NaCl stress in
      contrast to Arabidopsis. Notably a large number of known abiotic- and biotic
      stress inducible genes, including Fe-SOD, P5CS, PDF1.2, AtNCED, P-protein, beta
      glucosidase, and SOS1, were expressed in salt cress at high levels even in the
      absence of stress. Under normal growing conditions, salt cress accumulated Pro at
      much higher levels than did Arabidopsis, and this corresponded to a higher
      expression of AtP5CS in salt cress, a key enzyme of Pro biosynthesis.
      Furthermore, salt cress was more tolerant to oxidative stress than Arabidopsis.
      Stress tolerance of salt cress may be due to constitutive overexpression of many
      genes that function in stress tolerance and that are stress inducible in
      Arabidopsis.

PMID- 15247403
TI  - Cloning and characterization of two NAD kinases from Arabidopsis. identification
      of a calmodulin binding isoform.
AB  - NAD kinase (NADK; ATP:NAD 2'-phosphotransferase, EC 2.7.1.23), an enzyme found in
      both prokaryotes and eukaryotes, generates the important pyridine nucleotide NADP
      from substrates ATP and NAD. The role of NADKs in plants is poorly understood,
      and cDNAs encoding plant NADKs have not previously been described to our
      knowledge. We have cloned two cDNAs from Arabidopsis predicted to encode NADK
      isoforms, designated NADK1 and NADK2, respectively. Expressed as recombinant
      proteins in bacteria, both NADK1 and NADK2 were catalytically active, thereby
      confirming their identity as NADKs. Transcripts for both isoforms were detected
      in all tissues examined and throughout development. Although the predicted
      catalytic regions for NADK1 and NADK2 show sequence similarity to NADKs from
      other organisms, NADK2 possesses a large N-terminal extension that appears to be
      unique to plants. Using recombinant glutathione-S-transferase fusion proteins and
      calmodulin (CaM)-affinity chromatography, we delineated a Ca2+-dependent CaM
      binding domain to a 45-residue region within the N-terminal extension of NADK2.
      Although recombinant NADK2 was not responsive to CaM in vitro, immunoblot
      analysis suggests that native NADK2 is a CaM-binding protein. In Arabidopsis
      crude extracts, CaM-dependent NADK activity was much greater than CaM-independent
      activity throughout development, particularly in young seedlings. A native CaM
      dependent NADK was partially purified from Arabidopsis seedlings (Km NAD=0.20 mM,
      Km Mg2+ -ATP=0.17 mM). The enzyme was fully activated by conserved CaM (S0.5 =
      2.2 nm) in the presence of calcium but displayed differential responsiveness to
      eight CaM-like Arabidopsis proteins. Possible roles for NADKs in plants are
      discussed in light of our observations.

PMID- 15247404
TI  - beta-Amylase induction and the protective role of maltose during temperature
      shock.
AB  - A number of studies have demonstrated beta-amylase induction in response to
      abiotic stress. In the present work, a temperature response profile in 5 degrees
      C increments from 45 degrees C to 0 degrees C showed that induction at
      temperature extremes was specific for two members of the gene family (BMY7 and
      BMY8). Both members encode proteins that possess apparent transit peptides for
      chloroplast stromal localization. However, induction was not observed for other
      key starch degrading enzymes demonstrating a rather specific response to
      temperature stress for BMY7 and BMY8. Time course experiments for heat shock at
      40 degrees C and cold shock at 5 degrees C showed that beta-amylase induction
      correlated with maltose accumulation. Maltose has the ability, as demonstrated by
      in vitro assays, to protect proteins, membranes, and the photosynthetic electron
      transport chain at physiologically relevant concentrations. Therefore, beta
      amylase induction and the resultant maltose accumulation may function as a
      compatible-solute stabilizing factor in the chloroplast stroma in response to
      acute temperature stress.

PMID- 15247405
TI  - Floral meristem identity genes are expressed during tendril development in
      grapevine.
AB  - To study the early steps of flower initiation and development in grapevine (Vitis
      vinifera), we have isolated two MADS-box genes, VFUL-L and VAP1, the putative FUL
      like and AP1 grapevine orthologs, and analyzed their expression patterns during
      vegetative and reproductive development. Both genes are expressed in lateral
      meristems that, in grapevine, can give rise to either inflorescences or tendrils.
      They are also coexpressed in inflorescence and flower meristems. During flower
      development, VFUL-L transcripts are restricted to the central part of young
      flower meristems and, later, to the prospective carpel-forming region, which is
      consistent with a role of this gene in floral transition and carpel and fruit
      development. Expression pattern of VAP1 suggests that it may play a role in
      flowering transition and flower development. However, its lack of expression in
      sepal primordia, does not support its role as an A-function gene in grapevine.
      Neither VFUL-L nor VAP1 expression was detected in vegetative organs such as
      leaves or roots. In contrast, they are expressed throughout tendril development.
      Transcription of both genes in tendrils of very young plants that have not
      undergone flowering transition indicates that this expression is independent of
      the flowering process. These unique expression patterns of genes typically
      involved in reproductive development have implications on our understanding of
      flower induction and initiation in grapevine, on the origin of grapevine tendrils
      and on the functional roles of AP1-and FUL-like genes in plant development. These
      results also provide molecular support to the hypothesis that Vitis tendrils are
      modified reproductive organs adapted to climb.

PMID- 15247406
TI  - Root-gel interactions and the root waving behavior of Arabidopsis.
AB  - Arabidopsis roots grown on inclined agarose gels exhibit a sinusoidal growth
      pattern known as root waving. While root waving has been attributed to both
      intrinsic factors (e.g. circumnutation) and growth responses to external signals
      such as gravity, the potential for physical interactions between the root and its
      substrate to influence the development of this complex phenotype has been
      generally ignored. Using a rotating stage microscope and time-lapse digital
      imaging, we show that (1) root tip mobility is impeded by the gel surface, (2)
      this impedance causes root tip deflections by amplifying curvature in the
      elongation zone in a way that is distinctly nontropic, and (3) root tip impedance
      is augmented by normal gravitropic pressure applied by the root tip against the
      gel surface. Thus, both lateral corrective bending near the root apex and root
      tip impedance could be due to different vector components of the same
      graviresponse. Furthermore, we speculate that coupling between root twisting and
      bending is a mechanical effect resulting from root tip impedance.

PMID- 15247407
TI  - The orf13 T-DNA gene of Agrobacterium rhizogenes confers meristematic competence
      to differentiated cells.
AB  - Plant infections by the soil bacterium Agrobacterium rhizogenes result in
      neoplastic disease with the formation of hairy roots at the site of infection.
      Expression of a set of oncogenes residing on the stably integrated T-DNA is
      responsible for the disease symptoms. Besides the rol (root locus) genes, which
      are essential for the formation of hairy roots, the open reading frame orf13
      mediates cytokinin-like effects, suggesting an interaction with hormone signaling
      pathways. Here we show that ORF13 induced ectopic expression of KNOX (KNOTTED1
      like homeobox) class transcription factors, as well as of several genes involved
      in cell cycle control in tomato (Lycopersicon esculentum). ORF13 has a
      retinoblastoma (RB)-binding motif and interacted with maize (Zea mays) RB in
      vitro, whereas ORF13, bearing a point mutation in the RB-binding motif (ORF13*),
      did not. Increased cell divisions in the vegetative shoot apical meristem and
      accelerated formation of leaf primordia were observed in plants expressing orf13,
      whereas the expression of orf13* had no influence on cell division rates in the
      shoot apical meristem, suggesting a role of RB in the regulation of the cell
      cycle in meristematic tissues. On the other hand, ectopic expression of LeT6 was
      not dependent on a functional RB-binding motif. Hormone homeostasis was only
      altered in explants of leaves, whereas in the root no effects were observed. We
      suggest that ORF13 confers meristematic competence to cells infected by A.
      rhizogenes by inducing the expression of KNOX genes and promotes the transition
      of infected cells from the G1 to the S phase by binding to RB.

PMID- 15247408
TI  - Phloem import and storage metabolism are highly coordinated by the low oxygen
      concentrations within developing wheat seeds.
AB  - We studied the influence of the internal oxygen concentration in seeds of wheat
      (Triticum aestivum) on storage metabolism and its relation to phloem import of
      nutrients. Wheat seeds that were developing at ambient oxygen (21%) were found to
      be hypoxic (2.1%). Altering the oxygen supply by decreasing or increasing the
      external oxygen concentration induced parallel changes in the internal oxygen
      tension. However, the decrease in internal concentration was proportionally less
      than the reduction in external oxygen. This indicates that decreasing the oxygen
      supply induces short-term adaptive responses to reduce oxygen consumption of the
      seeds. When external oxygen was decreased to 8%, internal oxygen decreased to
      approximately 0.5% leading to a decrease in energy production via respiration.
      Conversely, increasing the external oxygen concentration above ambient levels
      increased the oxygen content as well as the energy status of the seeds,
      indicating that under normal conditions the oxygen supply is strongly limiting
      for energy metabolism in developing wheat seeds. The intermediate metabolites of
      seed storage metabolism were not substantially affected when oxygen was either
      increased or decreased. However, at subambient external oxygen concentrations
      (8%) the metabolic flux of carbon into starch and protein, measured by injecting
      (14)C-Suc into the seeds, was reduced by 17% and 32%, respectively, whereas no
      significant effect was observed at superambient (40%) oxygen. The observed
      decrease in biosynthetic fluxes to storage compounds is suggested to be part of
      an adaptive response to reduce energy consumption preventing excessive oxygen
      consumption when oxygen supply is limited. Phloem transport toward ears exposed
      to low (8%) oxygen was significantly reduced within 1 h, whereas exposing ears to
      elevated oxygen (40%) had no significant effect. This contrasts with the
      situation where the distribution of assimilates has been modified by removing the
      lower source leaves from the plant, resulting in less assimilates transported to
      the ear in favor of transport to the lower parts of the plant. Under these
      conditions, with two strongly competing sinks, elevated oxygen (40%) did lead to
      a strong increase in phloem transport to the ear. The results show that sink
      metabolism is affected by the prevailing low oxygen concentrations in developing
      wheat seeds, determining the import rate of assimilates via the phloem.

PMID- 15247409
TI  - The ANTHER INDEHISCENCE1 gene encoding a single MYB domain protein is involved in
      anther development in rice.
AB  - Using a two-element iAc/Ds transposon-tagging system, we identified a rice (Oryza
      sativa L. cv Nipponbare) recessive mutant, anther indehiscence1 (aid1), showing
      partial to complete spikelet sterility. Spikelets of the aid1 mutant could be
      classified into three types based on the viability of pollen grains and the
      extent of anther dehiscence. Type 1 spikelets (approximately 25%) were sterile
      due to a failure in accumulation of starch in pollen grains. Type 2 spikelets
      (approximately 55%) had viable pollen grains, but anthers failed to dehisce
      and/or synchronize with anthesis due to failure in septum degradation and stomium
      breakage, resulting in sterility. Type 3 spikelets (approximately 20%) had normal
      fertility. In addition, aid1 mutant plants had fewer tillers and flowered 10 to
      15 d later than the wild type. The Ds insertion responsible for the aid1 mutation
      was mapped within the coding region of the AID1 gene on chromosome 6, which is
      predicted to encode a novel protein of 426 amino acids with a single MYB domain.
      The MYB domain of AID1 is closely related to that of the telomere-binding
      proteins of human, mouse, and Arabidopsis, and of single MYB domain
      transcriptional regulators in plants such as PcMYB1 and ZmIBP1. AID1 was
      expressed in both the leaves and panicles of wild-type plants, but not in mutant
      plants.

PMID- 15247410
TI  - Identification and characterization of stretch-activated ion channels in pollen
      protoplasts.
AB  - Pollen tube growth requires a Ca2+ gradient, with elevated levels of cytosolic
      Ca2+ at the growing tip. This gradient's magnitude oscillates with growth
      oscillation but is always maintained. Ca2+ influx into the growing tip is
      necessary, and its magnitude also oscillates with growth. It has been widely
      assumed that stretch-activated Ca2+ channels underlie this influx, but such
      channels have never been reported in either pollen grains or pollen tubes. We
      have identified and characterized stretch-activated Ca2+ channels from Lilium
      longiflorum pollen grain and tube tip protoplasts. The channels were localized to
      a small region of the grain protoplasts associated with the site of tube
      germination. In addition, we find a stretch-activated K+ channel as well as a
      spontaneous K+ channel distributed over the entire grain surface, but neither was
      present at the germination site or at the tip. Neither stretch-activated channel
      was detected in the grain protoplasts unless the grains were left in germination
      medium for at least 1 h before protoplast preparation. The stretch-activated
      channels were inhibited by a spider venom that is known to block stretch
      activated channels in animal cells, but the spontaneous channel was unaffected by
      the venom. The venom also stopped pollen tube germination and elongation and
      blocked Ca2+ entry into the growing tip, suggesting that channel function is
      necessary for growth.

PMID- 15247411
TI  - Vasorin, a transforming growth factor beta-binding protein expressed in vascular
      smooth muscle cells, modulates the arterial response to injury in vivo.
AB  - Growth factors, cell-surface receptors, adhesion molecules, and extracellular
      matrix proteins play critical roles in vascular pathophysiology by affecting
      growth, migration, differentiation, and survival of vascular cells. In a search
      for secreted and cell-surface molecules expressed in the cardiovascular system,
      by using a retrovirus-mediated signal sequence trap method, we isolated a cell
      surface protein named vasorin. Vasorin is a typical type I membrane protein,
      containing tandem arrays of a characteristic leucine-rich repeat motif, an
      epidermal growth factor-like motif, and a fibronectin type III-like motif at the
      extracellular domain. Expression analyses demonstrated that vasorin is
      predominantly expressed in vascular smooth muscle cells, and that its expression
      is developmentally regulated. To clarify biological functions of vasorin, we
      searched for its binding partners and found that vasorin directly binds to
      transforming growth factor (TGF)-beta and attenuates TGF-beta signaling in vitro.
      Vasorin expression was down-regulated during vessel repair after arterial injury,
      and reversal of vasorin down-regulation, by using adenovirus-mediated in vivo
      gene transfer, significantly diminished injury-induced vascular lesion formation,
      at least in part, by inhibiting TGF-beta signaling in vivo. These results suggest
      that down-regulation of vasorin expression contributes to neointimal formation
      after vascular injury and that vasorin modulates cellular responses to
      pathological stimuli in the vessel wall. Thus, vasorin is a potential therapeutic
      target for vascular fibroproliferative disorders.

PMID- 15247412
TI  - Absence of a reductase, NCB5OR, causes insulin-deficient diabetes.
AB  - NCB5OR is a highly conserved NAD(P)H reductase that contains a cytochrome b5-like
      domain at the N terminus and a cytochrome b5 reductase-like domain at the C
      terminus. The enzyme is located in the endoplasmic reticulum (ER) and is widely
      expressed in organs and tissues. Targeted inactivation of this gene in mice has
      no impact on embryonic or fetal viability. At 4 weeks of age, Ncb5or-/- mice have
      normal blood glucose levels but impaired glucose tolerance. Isolated Ncb5or-/-
      islets have markedly impaired glucose- or arginine-stimulated insulin secretion.
      By 7 weeks of age, these mice develop severe hyperglycemia with markedly
      decreased serum insulin levels and nearly normal insulin tolerance. As the
      animals age, there is a progressive loss of beta cells in pancreatic islets, but
      there is no loss of alpha, delta, or PP cells. Electron microscopy reveals
      degranulation of beta cells and hypertrophic and hyperplastic mitochondria, some
      of which contain electron dense inclusions. Four-week-old Ncb5or-/- mice have
      enhanced sensitivity to the diabetogenic agent streptozotocin. NCB5OR appears to
      play a critical role in protecting pancreatic beta cells against oxidant stress.

PMID- 15247413
TI  - Protozoan predation, diversifying selection, and the evolution of antigenic
      diversity in Salmonella.
AB  - Extensive population-level genetic variability at the Salmonella rfb locus, which
      encodes enzymes responsible for synthesis of the O-antigen polysaccharide, is
      thought to have arisen through frequency-dependent selection (FDS) by means of
      exposure of this pathogen to host immune systems. The FDS hypothesis works well
      for pathogens such as Haemophilus influenzae and Neisseria meningitis, which
      alter the composition of their O-antigens during the course of bloodborne
      infections. In contrast, Salmonella remains resident in epithelial cells or
      macrophages during infection and does not have phase variability in its O
      antigen. More importantly, Salmonella shows host-serovar specificity, whereby
      strains bearing certain O-antigens cause disease primarily in specific hosts;
      this behavior is inconsistent with FDS providing selection for the origin or
      maintenance of extensive polymorphism at the rfb locus. Alternatively, selective
      pressure may originate from the host intestinal environment itself, wherein
      diversifying selection mediated by protozoan predation allows for the continued
      existence of Salmonella able to avoid consumption by host-specific protozoa. This
      selective pressure would result in high population-level diversity at the
      Salmonella rfb locus without phase variation. We show here that intestinal
      protozoa recognize antigenically diverse Salmonella with different efficiencies
      and demonstrate that differences solely in the O-antigen are sufficient to allow
      for prey discrimination. Combined with observations of the differential
      distributions of both serotypes of bacterial species and their protozoan
      predators among environments, our data provides a framework for the evolution of
      high genetic diversity at the rfb locus and host-specific pathogenicity in
      Salmonella.

PMID- 15247414
TI  - Varicella-zoster virus infection of human neural cells in vivo.
AB  - Varicella-zoster virus (VZV) establishes latency in sensory ganglia and causes
      herpes zoster upon reactivation. These investigations in a nonobese diabetic
      severe combined immunodeficient mouse-human neural cell model showed that VZV
      infected both neurons and glial cells and spread efficiently from cell to cell in
      vivo. Neural cell morphology and protein synthesis were preserved, in contrast to
      destruction of epithelial cells by VZV. Expression of VZV genes in neural cells
      was characterized by nuclear retention of the major viral transactivating protein
      and a block in synthesis of the predominant envelope glycoprotein. The attenuated
      VZV vaccine strain retained infectivity for neurons and glial cells in vivo. VZV
      gene expression in differentiated human neural cells in vivo differs from neural
      infection by herpes simplex virus, which is characterized by latency-associated
      transcripts, and from lytic VZV replication in skin. The chimeric nonobese
      diabetic severe combined immunodeficient mouse model may be useful for
      investigating other neurotropic human viruses.

PMID- 15247415
TI  - MS analysis of single-nucleotide differences in circulating nucleic acids:
      Application to noninvasive prenatal diagnosis.
AB  - The analysis of circulating nucleic acids has revealed applications in the
      noninvasive diagnosis, monitoring, and prognostication of many clinical
      conditions. Circulating fetal-specific sequences have been detected and
      constitute a fraction of the total DNA in maternal plasma. The diagnostic
      reliability of circulating DNA analysis depends on the fractional concentration
      of the targeted sequence, the analytical sensitivity, and the specificity. The
      robust discrimination of single-nucleotide differences between circulating DNA
      species is technically challenging and demands the adoption of highly sensitive
      and specific analytical systems. We have developed a method based on single
      allele base extension reaction and MS, which allows for the reliable detection of
      fetal-specific alleles, including point mutations and single-nucleotide
      polymorphisms, in maternal plasma. The approach was applied to exclude the fetal
      inheritance of the four most common Southeast Asian beta-thalassemia mutations in
      at-risk pregnancies between weeks 7 and 21 of gestation. Fetal genotypes were
      correctly predicted in all cases studied. Fetal haplotype analysis based on a
      single-nucleotide polymorphism linked to the beta-globin locus, HBB, in maternal
      plasma also was achieved. Consequently, noninvasive prenatal diagnosis in a
      mother and father carrying identical beta-thalassemia mutations was accomplished.
      These advances will help in catalyzing the clinical applications of fetal nucleic
      acids in maternal plasma. This analytical approach also will have implications
      for many other applications of circulating nucleic acids in areas such as
      oncology and transplantation.

PMID- 15247416
TI  - Emx2 homeodomain transcription factor interacts with eukaryotic translation
      initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons.
AB  - We report that Emx2 homeogene is expressed at the mRNA and protein levels in the
      adult mouse olfactory neuroepithelium. As expected for a transcription factor,
      Emx2 is present in the nucleus of immature and mature olfactory sensory neurons.
      However, the protein is also detected in the axonal compartment of these neurons,
      both in the olfactory mucosa axon bundles and in axon terminals within the
      olfactory bulb. Emx2 axonal staining is heterogeneous, suggesting an association
      with particles. Subcellular fractionations of olfactory bulb synaptosomes,
      combined with chemical lesions of olfactory neurons, confirm the presence of Emx2
      in axon terminals. Significant amounts of Emx2 protein cosediment with high
      density synaptosomal subfractions containing eukaryotic translation initiation
      factor 4E (eIF4E). Nonionic detergents and RNase treatments failed to detach
      eIF4E and Emx2 from these high-density fractions enriched in vesicles and
      granular structures. In addition, Emx2 and eIF4E can be coimmunoprecipitated from
      olfactory mucosa and bulb extracts and interact directly, as demonstrated in pull
      down experiments. Emx2 axonal localization, association with high-density
      particles and interaction with eIF4E strongly suggest that this transcription
      factor has new nonnuclear functions most probably related to the local control of
      protein translation in the olfactory sensory neuron axons. Finally, we show that
      two other brain-expressed homeoproteins, Otx2 and Engrailed 2, also bind eIF4E,
      indicating that several homeoproteins may modulate eIF4E functions in the
      developing and adult nervous system.

PMID- 15247417
TI  - Charge equilibration between two distinct sites in double helical DNA.
AB  - DNA assemblies containing a pendant dipyridophenazine complex of Ru(II) along
      with two oxidative traps, a site containing the nucleoside analog methylindole
      (5'-GMG-3') and a 5'-GGG-3' site, have been constructed to explore long-range
      charge transport through the base pair stack. With these chemically well defined
      assemblies, in combination with the flash/quench technique, formation of the
      methylindole cation radical and the neutral guanine radical is monitored directly
      by using transient absorption spectroscopy, and yields of oxidative damage are
      quantitated biochemically by gel electrophoresis. In these assemblies the base
      radicals form with a rate of > or =10(7) s(-1). The rate of base radical
      formation does not change upon the addition of a second radical trap, the 5'-GGG
      3' site; however, the yield of methylindole oxidation is significantly lower.
      This observation indicates that the 5'-GGG-3' site is effective in competing for
      the migrating charge and provides a second trapping site. Switching the
      orientation of the two trapping sites does not affect the yield of oxidized
      products at either site. Therefore, in DNA both forward and reverse charge
      transport occur so as to provide equilibration across the duplex on a timescale
      that is fast compared with trapping at a particular site. Further evidence of
      charge equilibration results from incorporating an intervening base-stacking
      perturbation and monitoring the fate of the injected charge. These experiments
      underscore the dynamic nature of DNA charge transport and reveal the importance
      of considering radical propagation in both directions along the DNA duplex.

PMID- 15247418
TI  - Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress
      mitochondrial transcription and replication.
AB  - Defects in mitochondrial oxidative phosphorylation have frequently been
      associated with Alzheimer's disease (AD), and both inherited and somatic mtDNA
      mutations have been reported in certain AD cases. To determine whether mtDNA
      mutations contribute more generally to the etiology of AD, we have investigated
      the sequence of the mtDNA control region (CR) from AD brains for possible disease
      causing mutations. Sixty-five percent of the AD brains harbored the T414G
      mutation, whereas this mutation was absent from all controls. Moreover, cloning
      and sequencing of the mtDNA CR from patient and control brains revealed that all
      AD brains had an average 63% increase in heteroplasmic mtDNA CR mutations and
      that AD brains from patients 80 years and older had a 130% increase in
      heteroplasmic CR mutations. In addition, these mutations preferentially altered
      known mtDNA regulatory elements. Certain AD brains harbored the disease-specific
      CR mutations T414C and T477C, and several AD brains between 74 and 83 years of
      age harbored the CR mutations T477C, T146C, and T195C, at levels up to 70-80%
      heteroplasmy. AD patient brains also had an average 50% reduction in the mtDNA L
      strand ND6 transcript and in the mtDNA/nuclear DNA ratio. Because reduced ND6
      mRNA and mtDNA copy numbers would reduce brain oxidative phosphorylation, these
      CR mutations could account for some of the mitochondrial defects observed in AD.

PMID- 15247419
TI  - Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid
      metabolites.
AB  - Ethanol causes pancreatic damage by an unknown mechanism. Previously, we
      demonstrated that a sustained rise of the cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) causes pancreatic acinar cell injury. Here we have investigated the
      effects of ethanol and its metabolites on Ca(2+) signaling in pancreatic acinar
      cells. Most cells exposed to ethanol (up to 850 mM) showed little or no increase
      in [Ca(2+)](i) (and never at concentrations <50 mM). During sustained exposure to
      850 mM ethanol, acetylcholine (ACh) evoked a normal [Ca(2+)](i) elevation and
      following ACh removal there was a normal and rapid recovery to a low resting
      level. The oxidative metabolite acetaldehyde (up to 5 mM) had no effect, whereas
      the nonoxidative unsaturated metabolite palmitoleic acid ethyl ester (10-100
      microM, added on top of 850 mM ethanol) induced sustained, concentration
      dependent increases in [Ca(2+)](i) that were acutely dependent on external Ca(2+)
      and caused cell death. These actions were shared by the unsaturated metabolite
      arachidonic acid ethyl ester, the saturated equivalents palmitic and arachidic
      acid ethyl esters, and the fatty acid palmitoleic acid. In the absence of
      external Ca(2+), releasing all Ca(2+) from the endoplasmic reticulum by ACh (10
      microM) or the specific Ca(2+) pump inhibitor thapsigargin (2 microM) prevented
      such Ca(2+) signal generation. We conclude that nonoxidative fatty acid
      metabolites, rather than ethanol itself, are responsible for the marked
      elevations of [Ca(2+)](i) that mediate toxicity in the pancreatic acinar cell and
      that these compounds act primarily by releasing Ca(2+) from the endoplasmic
      reticulum.

PMID- 15247420
TI  - NFAT5/TonEBP mutant mice define osmotic stress as a critical feature of the
      lymphoid microenvironment.
AB  - Osmotic stress responses are critical not only to the survival of unicellular
      organisms but also to the normal function of the mammalian kidney. However, the
      extent to which cells outside the kidney rely on osmotic stress responses in vivo
      remains unknown. Nuclear factor of activated T cells 5 (NFAT5)/tonicity enhancer
      binding protein (TonEBP), the only known osmosensitive mammalian transcription
      factor, is expressed most abundantly in the thymus and is induced upon lymphocyte
      activation. Here we report that NFAT5/TonEBP is not only essential for normal
      cell proliferation under hyperosmotic conditions but also necessary for optimal
      adaptive immunity. Targeted deletion of exons 6 and 7 of the Nfat5 gene, which
      encode a critical region of the DNA-binding domain, gave rise to a complete loss
      of function in the homozygous state and a partial loss of function in the
      heterozygous state. Complete loss of function resulted in late gestational
      lethality. Furthermore, hypertonicity-induced NFAT5/TonEBP transcriptional
      activity and hsp70.1 promoter function were completely eliminated, and cell
      proliferation under hyperosmotic culture conditions was markedly impaired.
      Partial loss of NFAT5/TonEBP function resulted in lymphoid hypocellularity and
      impaired antigen-specific antibody responses in viable heterozygous animals. In
      addition, lymphocyte proliferation ex vivo was reduced under hypertonic, but not
      isotonic, culture conditions. Direct measurement of tissue osmolality further
      revealed lymphoid tissues to be hyperosmolar. These results indicate that
      lymphocyte-mediated immunity is contingent on adaptation to physiologic osmotic
      stress, thus providing insight into the lymphoid microenvironment and the
      importance of the NFAT5/TonEBP osmotic stress response pathway in vivo.

PMID- 15247421
TI  - Directed evolution of ligand dependence: small-molecule-activated protein
      splicing.
AB  - Artificial molecular switches that modulate protein activities in response to
      synthetic small molecules would serve as tools for exerting temporal and dose
      dependent control over protein function. Self-splicing protein elements (inteins)
      are attractive starting points for the creation of such switches, because their
      insertion into a protein blocks the target protein's function until splicing
      occurs. Natural inteins, however, are not known to be regulated by small
      molecules. We evolved an intein-based molecular switch that transduces binding of
      a small molecule into the activation of an arbitrary protein of interest. Simple
      insertion of a natural ligand-binding domain into a minimal intein destroys
      splicing activity. To restore activity in a ligand-dependent manner, we linked
      protein splicing to cell survival or fluorescence in Saccharomyces cerevisiae.
      Iterated cycles of mutagenesis and selection yielded inteins with strong splicing
      activities that highly depend on 4-hydroxytamoxifen. Insertion of an evolved
      intein into four unrelated proteins in living cells revealed that ligand
      dependent activation of protein function is general, fairly rapid, dose
      dependent, and posttranslational. Our directed-evolution approach therefore
      evolved small-molecule dependence in a protein and also created a general tool
      for modulating the function of arbitrary proteins in living cells with a single
      cell-permeable, synthetic small molecule.

PMID- 15247422
TI  - The effects of host contact network structure on pathogen diversity and strain
      structure.
AB  - For many important pathogens, mechanisms promoting antigenic variation, such as
      mutation and recombination, facilitate immune evasion and promote strain
      diversity. However, mathematical models have shown that host immune responses to
      polymorphic antigens can structure pathogen populations into discrete strains
      with nonoverlapping antigenic repertoires, despite recombination. Until now,
      models of strain evolution incorporating host immunity have assumed a randomly
      mixed host population. Here, we illustrate the effects of different host contact
      networks on strain diversity and dynamics by using a stochastic, spatially
      heterogeneous analogue of this model. For randomly mixed populations, our model
      confirms that cross-immunity to strains sharing alleles at antigenic loci may
      structure the pathogen population into discrete, nonoverlapping strains. However,
      this structure breaks down once the assumption of random mixing is relaxed, and
      an increasingly diverse pathogen population emerges as contacts between hosts
      become more localized. These results imply that host contact network structure
      plays a significant role in mediating the emergence of pathogen strain structure
      and dynamics.

PMID- 15247423
TI  - Abnormal sperm in mice with targeted deletion of the act (activator of cAMP
      responsive element modulator in testis) gene.
AB  - ACT [activator of cAMP-responsive element modulator (CREM) in testis] is a LIM
      only protein that interacts with transcription factor CREM in postmeiotic male
      germ cells and enhances CREM-dependent transcription. CREM regulates many crucial
      genes required for spermatid maturation, and targeted mutation of the Crem gene
      in the mouse germ-line blocks spermatogenesis. Here we report the phenotype of
      mice in which targeted disruption of the act gene was obtained by homologous
      recombination. Whereas the seminiferous tubules of the act(-/-) mice contain all
      of the developmental stages of germ cells and the mice are fertile, the amount of
      mature sperm in the epididymis is drastically reduced. The residual sperm display
      severe abnormalities, including fully folded tails and aberrant head shapes.
      These results indicate that numerous postmeiotic genes under CREM control require
      the coactivator function of ACT. Thus, the fine-tuning of sperm development is
      achieved by the coordinated action of two transcriptional regulators.

PMID- 15247424
TI  - Direct measurement of proton release by cytochrome c oxidase in solution during
      the F-->O transition.
AB  - The mechanism by which electron transfer is coupled to proton pumping in
      cytochrome c oxidase is a major unsolved problem in molecular bioenergetics. In
      this work it is shown that, at least under some conditions, proton release from
      the enzyme occurs before proton uptake upon electron transfer to the heme/Cu
      active site of the enzyme. This sequence is similar to that of proton release and
      uptake observed for the light-activated proton pump bacteriorhodopsin. In the
      case of cytochrome c oxidase, this observation means that both the ejected proton
      and the proton required for the chemistry at the enzyme active site must come
      from an internal proton pool.

PMID- 15247425
TI  - The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway
      serpin.
AB  - Proprotein convertases (PCs) are an important class of host-cell serine
      endoproteases implicated in many physiological and pathological processes. Owing
      to their expanding roles in the proteolytic events required for generating
      infectious microbial pathogens and for tumor growth and invasiveness, there is
      increasing interest in identifying endogenous PC inhibitors. Here we report the
      identification of Spn4A, a previously uncharacterized secretory pathway serine
      protease inhibitor (serpin) from Drosophila melanogaster that contains a
      consensus furin cleavage site, -Arg(P4)-Arg-Lys-Arg(P1) downsream-, in its
      reactive site loop (RSL). Our biochemical and kinetics analysis revealed that
      recombinant Spn4A inhibits human furin (K(i), 13 pM; k(ass), 3.2 x 10(7) M(-1) x
      s(-1)) and Drosophila PC2 (K(i), 3.5 nM; k(ass), 9.2 x 10(4) M(-1) x s(-1)) by a
      slow-binding mechanism characteristic of serpin molecules and forms a kinetically
      trapped SDS-stable complex with each enzyme. For both PCs, the stoichiometry of
      inhibition by Spn4A is nearly 1, which is characteristic of known physiological
      serpin-protease interactions. Mass analysis of furin-Spn4A reaction products
      identified the actual reactive site center of Spn4A to be -Arg(P4)-Arg-Lys
      Arg(P1)-downstream-. Moreover, we demonstrate that Spn4A's highly effective PC
      inhibition properties are critically dependent on the unusual length of its RSL,
      which is composed of 18 aa instead of the typical 17-residue RSL found in most
      other inhibitory serpins. The identification of Spn4A, the most potent and
      effective natural serpin of PCs identified to date, suggests that Spn4A could be
      a prototype of endogenous serpins involved in the precise regulation of PC
      dependent proteolytic cleavage events in the secretory pathway of eukaryotic
      cells.

PMID- 15247426
TI  - Functional disassociation of the central and peripheral fatty acid amide
      signaling systems.
AB  - Fatty acid amides (FAAs) constitute a large class of endogenous signaling lipids
      that modulate several physiological processes, including pain, feeding, blood
      pressure, sleep, and inflammation. Although FAAs have been proposed to evoke
      their behavioral effects through both central and peripheral mechanisms, these
      distinct signaling pathways have remained experimentally challenging to separate.
      Here, we report a transgenic mouse model in which the central and peripheral FAA
      systems have been functionally uncoupled. Mice were generated that express the
      principle FAA-degrading enzyme FAA hydrolase (FAAH) specifically in the nervous
      system (FAAH-NS mice) by crossing FAAH(-/-) mice with transgenic mice that
      express FAAH under the neural specific enolase promoter. FAAH-NS mice were found
      to possess wild-type levels of FAAs in the brain and spinal cord, but
      significantly elevated concentrations of these lipid transmitters in peripheral
      tissues. This anatomically restricted biochemical phenotype correlated with a
      reversion of the reduced pain sensitivity of FAAH(-/-) mice, consistent with the
      FAA anandamide producing this effect by acting on cannabinoid receptors in the
      nervous system. Interestingly, however, FAAH-NS mice still exhibited an
      antiinflammatory phenotype similar in magnitude to FAAH(-/-) mice, indicating
      that this activity, which was not blocked by cannabinoid receptor antagonists,
      was mediated by peripherally elevated FAAs. These data suggest that the central
      and peripheral FAA signaling systems regulate discrete behavioral processes and
      may be targeted for distinct therapeutic gain.

PMID- 15247427
TI  - NFAT is a nerve activity sensor in skeletal muscle and controls activity
      dependent myosin switching.
AB  - Calcineurin (Cn) signaling has been implicated in nerve activity-dependent fiber
      type specification in skeletal muscle, but the downstream effector pathway has
      not been established. We have investigated the role of the transcription factor
      nuclear factor of activated T cells (NFAT), a major target of Cn, by using an in
      vivo transfection approach in regenerating and adult rat muscles. NFAT
      transcriptional activity was monitored with two different NFAT-dependent
      reporters and was found to be higher in slow compared to fast muscles. NFAT
      activity is decreased by denervation in slow muscles and is increased by
      electrostimulation of denervated muscles with a tonic low-frequency impulse
      pattern, mimicking the firing pattern of slow motor neurons, but not with a
      phasic high-frequency pattern typical of fast motor neurons. To determine the
      role of NFAT, we transfected regenerating and adult rat muscles with a plasmid
      coding for VIVIT, a specific peptide inhibitor of Cn-mediated NFAT activation.
      VIVIT was found to block the expression of slow myosin heavy chain (MyHC-slow)
      induced by slow motor neuron activity in regenerating slow soleus muscle and to
      inhibit the expression of MyHC-slow transcripts and the activity of a MyHC-slow
      promoter in adult soleus. The role of NFAT was confirmed by the finding that a
      constitutively active NFATc1 mutant stimulates the MyHC-slow, inhibits the fast
      MyHC-2B promoter in adult fast muscles, and induces MyHC-slow expression in
      regenerating muscles. These results support the notion that Cn-NFAT signaling
      acts as a nerve activity sensor in skeletal muscle in vivo and controls nerve
      activity-dependent myosin switching.

PMID- 15247428
TI  - Expanded dynamic range of fluorescent indicators for Ca(2+) by circularly
      permuted yellow fluorescent proteins.
AB  - Fluorescence resonance energy transfer (FRET) technology has been used to develop
      genetically encoded fluorescent indicators for various cellular functions.
      Although most indicators have cyan- and yellow-emitting fluorescent proteins (CFP
      and YFP) as FRET donor and acceptor, their poor dynamic range often prevents
      detection of subtle but significant signals. Here, we optimized the relative
      orientation of the two chromophores in the Ca(2+) indicator, yellow cameleon
      (YC), by fusing YFP at different angles. We generated circularly permuted YFPs
      (cpYFPs) that showed efficient maturation and acid stability. One of the cpYFPs
      incorporated in YC absorbs a great amount of excited energy from CFP in its
      Ca(2+)-saturated form, thereby increasing the Ca(2+)-dependent change in the
      ratio of YFP/CFP by nearly 600%. Both in cultured cells and in the nervous system
      of transgenic mice, the new YC enables visualization of subcellular Ca(2+)
      dynamics with better spatial and temporal resolution than before. Our study
      provides an important guide for the development and improvement of indicators
      using GFP-based FRET.

PMID- 15247429
TI  - A reassessment of the response of the bacterial ribosome to the frameshift
      stimulatory signal of the human immunodeficiency virus type 1.
AB  - HIV-1 uses a programmed -1 ribosomal frameshift to produce the precursor of its
      enzymes. This frameshift occurs at a specific slippery sequence followed by a
      stimulatory signal, which was recently shown to be a two-stem helix, for which a
      three-purine bulge separates the upper and lower stems. In the present study, we
      investigated the response of the bacterial ribosome to this signal, using a
      translation system specialized for the expression of a firefly luciferase
      reporter. The HIV-1 frameshift region was inserted at the beginning of the coding
      sequence of the luciferase gene, such that its expression requires a -1
      frameshift. Mutations that disrupt the upper or the lower stem of the frameshift
      stimulatory signal or replace the purine bulge with pyrimidines decreased the
      frameshift efficiency, whereas compensatory mutations that re-form both stems
      restored the frame-shift efficiency to near wild-type level. These mutations had
      the same effect in a eukaryotic translation system, which shows that the
      bacterial ribosome responds like the eukaryote ribosome to the HIV-1 frameshift
      stimulatory signal. Also, we observed, in contrast to a previous report, that a
      stop codon immediately 3' to the slippery sequence does not decrease the
      frameshift efficiency, ruling out a proposal that the frameshift involves the
      deacylated-tRNA and the peptidyl-tRNA in the E and P sites of the ribosome,
      rather than the peptidyl-tRNA and the aminoacyl-tRNA in the P and A sites, as
      commonly assumed. Finally, mutations in 16S ribosomal RNA that facilitate the
      accommodation of the incoming aminoacyl-tRNA in the A site decreased the
      frameshift efficiency, which supports a previous suggestion that the frameshift
      occurs when the aminoacyl-tRNA occupies the A/T entry site.

PMID- 15247430
TI  - mRNA deadenylation by PARN is essential for embryogenesis in higher plants.
AB  - Deadenylation of mRNA is often the first and rate-limiting step in mRNA decay.
      PARN, a poly(A)-specific 3' --> 5' ribonuclease which is conserved in many
      eukaryotes, has been proposed to be primarily responsible for such a reaction,
      yet the importance of the PARN function at the whole-organism level has not been
      demonstrated in any species. Here, we show that mRNA deadenylation by PARN is
      essential for viability in higher plants (Arabidopsis thaliana). Yet, this
      essential requirement for the PARN function is not universal across the
      phylogenetic spectrum, because PARN is dispensable in Fungi (Schizosaccharomyces
      pombe), and can be at least severely downregulated without any obvious
      consequences in Metazoa (Caenorhabditis elegans). Development of the Arabidopsis
      embryos lacking PARN (AtPARN), as well as of those expressing an enzymatically
      inactive protein, was markedly retarded, and ultimately culminated in an arrest
      at the bent-cotyledon stage. Importantly, only some, rather than all, embryo
      specific transcripts were hyperadenylated in the mutant embryos, suggesting that
      preferential deadenylation of a specific select subset of mRNAs, rather than a
      general deadenylation of the whole mRNA population, by AtPARN is indispensable
      for embryogenesis in Arabidopsis. These findings indicate a unique, nonredundant
      role of AtPARN among the multiple plant deadenylases.

PMID- 15247431
TI  - Identification of a bifunctional enzyme MnmC involved in the biosynthesis of a
      hypermodified uridine in the wobble position of tRNA.
AB  - The gene encoding the bifunctional enzyme MnmC that catalyzes the two last steps
      in the biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm5s2U) in tRNA has
      been previously mapped at about 50 min on the Escherichia coli K12 chromosome,
      but to date the identity of the corresponding enzyme has not been correlated with
      any of the known open reading frames (ORFs). Using the protein fold-recognition
      approach, we predicted that the 74-kDa product of the yfcK ORF located at 52.6
      min and annotated as "putative peptidase" comprises a methyltransferase domain
      and a FAD-dependent oxidoreductase domain. We have cloned, expressed, and
      purified the YfcK protein and demonstrated that it catalyzes the formation of
      mnm5s2U in tRNA. Thus, we suggest to rename YfcK as MnmC.

PMID- 15247432
TI  - Origin, evolution, and mechanism of 5' tRNA editing in chytridiomycete fungi.
AB  - 5' tRNA editing has been demonstrated to occur in the mitochondria of the
      distantly related rhizopod amoeba Acanthamoeba castellanii and the
      chytridiomycete fungus Spizellomyces punctatus. In these organisms, canonical
      tRNA structures are restored by removing mismatched nucleotides at the first
      three 5' positions and replacing them with nucleotides capable of forming Watson
      Crick base pairs with their 3' counterparts. This form of editing seems likely to
      occur in members of Amoebozoa other than A. castellanii, as well as in members of
      Heterolobosea. Evidence for 5' tRNA editing has not been found to date, however,
      in any other fungus including the deeply branching chytridiomycete Allomyces
      macrogynus. We predicted that a similar form of tRNA editing would occur in
      members of the chytridiomycete order Monoblepharidales based on the analysis of
      complete mitochondrial tRNA complements. This prediction was confirmed by
      analysis of tRNA sequences using a tRNA circularization/RT-PCR-based approach.
      The presence of partially and completely unedited tRNAs in members of the
      Monoblepharidales suggests the involvement of a 5'-to-3' exonuclease rather than
      an endonuclease in removing the three 5' nucleotides from a tRNA substrate.
      Surprisingly, analysis of the mtDNA of the chytridiomycete Rhizophydium
      brooksianum, which branches as a sister group to S. punctatus in molecular
      phylogenies, did not suggest the presence of editing. This prediction was also
      confirmed experimentally. The absence of tRNA editing in R. brooksianum raises
      the possibility that 5' tRNA editing may have evolved twice independently within
      Chytridiomycota, once in the lineage leading to S. punctatus and once in the
      lineage leading to the Monoblepharidales.

PMID- 15247433
TI  - Isolation of specific and high-affinity RNA aptamers against NS3 helicase domain
      of hepatitis C virus.
AB  - Hepatitis C virus (HCV)-encoded nonstructural protein 3 (NS3) possesses protease,
      NTPase, and helicase activities, which are considered essential for viral
      proliferation. Thus, HCV NS3 is a good putative therapeutic target protein for
      the development of anti-HCV agents. In this study, we isolated specific RNA
      aptamers to the helicase domain of HCV NS3 from a combinatorial RNA library with
      40-nucleotide random sequences using in vitro selection techniques. The isolated
      RNAs were observed to very avidly bind the HCV helicase with an apparent Kd of
      990 pM in contrast to original pool RNAs with a Kd of >1 microM. These RNA
      ligands appear to impede binding of substrate RNA to the HCV helicase and can act
      as potent decoys to competitively inhibit helicase activity with high efficiency
      compared with poly(U) or tRNA. The minimal binding domain of the ligands was
      determined to evaluate the structural features of the isolated RNA molecules.
      Interestingly, part of binding motif of the RNA aptamers consists of similar
      secondary structure to the 3'-end of HCV negative-strand RNA. Moreover,
      intracellular NS3 protein can be specifically detected in situ with the RNA
      aptamers, indicating that the selected RNAs are very specific to the HCV NS3
      helicase. Furthermore, the RNA aptamers partially inhibited RNA synthesis of HCV
      subgenomic replicon in Huh-7 hepatoma cell lines. These results suggest that the
      RNA aptamers selected in vitro could be useful not only as therapeutic and
      diagnostic agents of HCV infection but also as a powerful tool for the study of
      HCV helicase mechanism.

PMID- 15247434
TI  - Multimerization of poly(rC) binding protein 2 is required for translation
      initiation mediated by a viral IRES.
AB  - The cellular protein, poly(rC) binding protein 2 (PCBP2), is known to function in
      picornavirus cap-independent translation. We have further examined the RNA
      binding properties and protein-protein interactions of PCBP2 necessary for
      translation. We have studied its putative multimerization properties utilizing
      the yeast two-hybrid assay and in vitro biochemical methods, including
      glutathione S-transferase (GST) pull-down assays and gel filtration. Through
      genetic analysis, the multimerization domain has been localized to the second K
      homologous (KH) RNA binding domain of the protein between amino acids 125 and
      158. To examine the function of multimerization in poliovirus translation, we
      utilized the truncated protein, DeltaKH1-PCBP2, which is capable of multimer
      formation, but does not bind poliovirus stem-loop IV RNA (an interaction required
      for translation). Utilizing RNA binding and in vitro translation assays, this
      protein was shown to act as a dominant negative, suggesting that PCBP2
      multimerization functions in poliovirus translation and RNA binding.
      Additionally, PCBP2 containing a deletion in the multimerization domain (DeltaKH2
      PCBP2) was not able to bind poliovirus stem-loop IV RNA and could not rescue
      translation in extracts that were depleted of endogenous PCBP2. Results from
      these experiments suggest that the multimerization of PCBP2 is required for
      efficient RNA binding and cap-independent translation of poliovirus RNA. By
      examining the functional interactions of the cellular protein PCBP2, we have
      discovered a novel determinant in the mechanism of picornavirus cap-independent
      translation.

PMID- 15247435
TI  - Nonadenomatous polyps at CT colonography: prevalence, size distribution, and
      detection rates.
AB  - PURPOSE: To prospectively investigate with computed tomographic (CT) colonography
      the prevalence and size distribution of nonadenomatous polyps in asymptomatic
      adults and to compare the detection rates of adenomatous and nonadenomatous
      polyps. MATERIALS AND METHODS: A total of 1233 asymptomatic adults (mean age,
      57.8 years; 505 women, 728 men) underwent same-day CT colonography and optical
      colonoscopy procedures. CT colonoscopy studies were interpreted prospectively
      with a primary three-dimensional approach immediately before optical colonoscopy.
      Statistical analysis was performed with the chi(2) test. Size, prevalence, and by
      polyp detection differences were compared between adenomatous and nonadenomatous
      polyps. RESULTS: Seven hundred fifty-six (57.7%) colorectal polyps identified at
      optical colonoscopy in 410 (33.3%) patients were nonadenomatous; of these
      lesions, 622 (82.3%) were diminutive (</=5 mm). Nonadenomatous polyps accounted
      for 622 (64.4%) of 966 diminutive lesions and 134 (39.9%) of 344 polyps 6 mm or
      larger (P <.001). The prevalence rate for nonadenomatous polyps was 8.8% (109 of
      1233 patients) and 2.0% (25 of 1233 patients) at 6- and 10-mm thresholds,
      respectively. CT colonography by-polyp sensitivity for nonadenomatous lesions was
      73.1% (98 of 134 patients) and 73.3% (22 of 30 patients) at 6- and 10-mm
      thresholds, respectively, compared with 85.7% (180 of 210 patients) and 92.2% (47
      of 51 patients) for adenomas (P <.01). In 1065 patients that did not have a 6-mm
      or larger adenoma at optical colonoscopy, CT colonography depicted a
      nonadenomatous polyp that was 6 mm or larger in 63 (5.9%) patients and a
      nonadenomatous polyp that was 10 mm or larger in 15 (1.4%) patients. CONCLUSION:
      More than 80% of nonadenomatous polyps were diminutive, but they accounted for
      nearly 40% of polyps that were 6 mm or larger. Fortunately, CT colonography is
      significantly (P <.01) less sensitive in the detection of lesions that have no
      malignant potential when compared with similar-sized adenomas that have malignant
      potential.

PMID- 15247436
TI  - Dynamic contrast-enhanced CT of intracranial meningioma: comparison of
      distributed and compartmental tracer kinetic models--initial results.
AB  - Dynamic contrast material-enhanced computed tomographic images of intracranial
      meningioma were analyzed by using both distributed-parameter and conventional
      compartmental tracer kinetic models. The distributed-parameter models were found
      to yield consistently better fitting of data sets than were conventional
      compartmental models. Although linear correlations were found between the kinetic
      parameters of the two models, some of these parameters (such as perfusion and
      mean transit time) did not correspond quantitatively. For all models, the kinetic
      parameters associated with the extravasation of tracer were found to be
      distinctly higher in meningiomas than in normal white- and gray-matter tissues.

PMID- 15247438
TI  - Mimicking surface plasmons with structured surfaces.
AB  - Metals such as silver support surface plasmons: electromagnetic surface
      excitations localized near the surface that originate from the free electrons of
      the metal. Surface modes are also observed on highly conducting surfaces
      perforated by holes. We establish a close connection between the two, showing
      that electromagnetic waves in both materials are governed by an effective
      permittivity of the same plasma form. The size and spacing of holes can readily
      be controlled on all relevant length scales, which allows the creation of
      designer surface plasmons with almost arbitrary dispersion in frequency and in
      space, opening new vistas in surface plasmon optics.

PMID- 15247439
TI  - A compound from smoke that promotes seed germination.
AB  - Exposure of seeds to aerosol smoke or crude smoke extracts stimulates the
      germination of a number of fire-dependent and fire-independent plant species. We
      now report the identity of a germination-promoting compound present in plant- and
      cellulose-derived smoke. The structure of this compound, deduced from
      spectroscopic analysis and confirmed by synthesis, was shown to be that of the
      butenolide 3-methyl-2H-furo[2,3-c]pyran-2-one (1). Here we show that 1 promotes
      germination of a number of plant species at a level similar to that observed with
      plant-derived smoke water.

PMID- 15247440
TI  - The global vaccination gap.

PMID- 15247437
TI  - Integrase inhibitors and cellular immunity suppress retroviral replication in
      rhesus macaques.
AB  - We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in
      rhesus macaques infected with the simian-human immunodeficiency virus (SHIV)
      89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a
      sustained suppression of viremia, preserving CD4 levels and permitting the
      induction of virus-specific cellular immunity. L-870812 was also active in
      chronic infection; however, the magnitude and durability of the effect varied in
      conjunction with the pretreatment immune response and viral load. These studies
      demonstrate integrase inhibitor activity in vivo and suggest that cellular
      immunity facilitates chemotherapeutic efficacy in retroviral infections.

PMID- 15247441
TI  - Obesity research. Labs fail to reproduce protein's appetite-suppressing effects.

PMID- 15247443
TI  - Geophysics. Hammered by India, puttylike Tibet shows limits of plate tectonics.

PMID- 15247442
TI  - Scientific community. U.S. prosecutes professors for shipping microbes.

PMID- 15247444
TI  - Neuroscience. Monkey see, monkey think about doing.

PMID- 15247445
TI  - Scientific meetings. Neuroscientists learn lesson in diplomacy.

PMID- 15247446
TI  - SARS. China dumps CDC head, probes lab.

PMID- 15247447
TI  - Planetary science. Cassini's magnificent machines run rings around Saturn.

PMID- 15247448
TI  - Oceanography. Saving Scripps.

PMID- 15247449
TI  - Oceanography. Other marine labs also paddle hard to stay afloat.

PMID- 15247450
TI  - Patient records. Privacy rule creates bottleneck for U.S. biomedical researchers.

PMID- 15247451
TI  - Immunotherapy. Can worms tame the immune system?

PMID- 15247452
TI  - Immunotherapy. Wielding worms at asthma and autoimmunity.

PMID- 15247453
TI  - Paleontology. Scientists warn of threats to fossil-rich Chinese site.

PMID- 15247454
TI  - U.S. science. Weak economy, higher stipends send more to graduate school.

PMID- 15247455
TI  - Support for the RV144 HIV vaccine trial.

PMID- 15247456
TI  - Outstanding questions on HIV vaccine trial.

PMID- 15247457
TI  - Comment on "Diverse psychotomimetics act through a common signaling pathway".

PMID- 15247459
TI  - Genetics. Genomic research and human subject privacy.

PMID- 15247460
TI  - Medicine. A boost for translational neuroscience.

PMID- 15247462
TI  - Physics. Woodpiles for photons.

PMID- 15247463
TI  - Molecular biology. Unraveling DNA condensation with optical tweezers.

PMID- 15247461
TI  - Immunology. Tracing an orphan's genealogy.

PMID- 15247464
TI  - Materials science. Microstructures in 4D.

PMID- 15247465
TI  - Genomics. The chimpanzee genome--a bittersweet celebration.

PMID- 15247467
TI  - Putting tolerance to the test.

PMID- 15247468
TI  - Immunotherapy: bewitched, bothered, and bewildered no more.
AB  - The field of immunotherapy holds clear promise not only for the development of
      new approaches to cancer and other diseases, but also for providing fundamental
      insight into the human immune response. In order for this promise to be realized,
      however, the scientific community must overcome an array of challenges. These
      challenges reflect not only the difficulties inherent in conducting
      investigations in human patients, but also difficulties created by the culture
      and practice of our own institutions, reward structure, and funding mechanisms.
      We suggest steps to be taken to reinvigorate basic research in human subjects as
      part of the mainstream of science.

PMID- 15247469
TI  - Cancer immunotherapy: a treatment for the masses.
AB  - Cancer immunotherapy attempts to harness the exquisite power and specificity of
      the immune system for the treatment of malignancy. Although cancer cells are less
      immunogenic than pathogens, the immune system is clearly capable of recognizing
      and eliminating tumor cells. However, tumors frequently interfere with the
      development and function of immune responses. Thus, the challenge for
      immunotherapy is to use advances in cellular and molecular immunology to develop
      strategies that effectively and safely augment antitumor responses.

PMID- 15247470
TI  - Therapeutic vaccines for chronic infections.
AB  - Therapeutic vaccines aim to prevent severe complications of a chronic infection
      by reinforcing host defenses when some immune control, albeit insufficient, can
      already be demonstrated and when a conventional antimicrobial therapy either is
      not available or has limited efficacy. We focus on the rationale and challenges
      behind this still controversial strategy and provide examples from three major
      chronic infectious diseases- human immunodeficiency virus, hepatitis B virus, and
      human papillomavirus-for which the efficacy of therapeutic vaccines is currently
      being evaluated.

PMID- 15247471
TI  - Exploiting tolerance processes in transplantation.
AB  - The full potential of organ transplantation has not yet been realized because of
      the hazards associated with the long-term use of immunosuppressive drugs. Modern
      research into mechanisms of immune tolerance offers the promise of reprogramming
      the immune system, so as to harness the body's natural tolerance mechanisms in
      the service of graft acceptance. This would allow the minimization of
      immunosuppressive treatment and offers the prospect of eventually weaning
      transplant recipients off their drugs.

PMID- 15247472
TI  - Immune therapy for autoimmune diseases.
AB  - Our increasing understanding of the pathophysiology of autoimmune disease has
      revealed a number of checkpoints that can be targeted with immune therapy,
      including key mediators of lymphocyte adhesion and migration, destructive
      cytokines involved in tissue damage, and the complex of molecules critical in the
      presentation of self-antigen and the activation of autoaggressive T lymphocytes.
      In many organ-specific autoimmune diseases, the identity of the molecules
      attacked by T cells and autoantibodies is known and attempts are under way to
      tolerize the immune system with a high level of specificity to these targets.

PMID- 15247473
TI  - Tryptophan hydroxylase-2 controls brain serotonin synthesis.
AB  - Dysregulation of brain serotonin contributes to many psychiatric disorders.
      Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in
      the brain. We report a functional (C1473G) single-nucleotide polymorphism in
      mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to
      decreased serotonin levels in PC12 cells. Moreover, in BALB/cJ and DBA/2 mice
      that are homozygous for the 1473G allele, brain serotonin tissue content and
      synthesis are reduced in comparison to C57Bl/6 and 129X1/SvJ mice that are
      homozygous for the 1473C allele. Our data provide direct evidence for a
      fundamental role of Tph2 in brain serotonin synthesis.

PMID- 15247474
TI  - Watching the growth of bulk grains during recrystallization of deformed metals.
AB  - We observed the in situ growth of a grain during recrystallization in the bulk of
      a deformed sample. We used the three-dimensional x-ray diffraction microscope
      located at the European Synchrotron Radiation Facility in Grenoble, France. The
      results showed a very heterogeneous growth pattern, contradicting the classical
      assumption of smooth and spherical growth of new grains during recrystallization.
      This type of in situ bulk measurement opens up the possibility of obtaining
      experimental data on scientific topics that before could only be analyzed
      theoretically on the basis of the statistical characterization of
      microstructures. For recrystallization, the in situ method includes direct
      measurements of nucleation and boundary migration through a deformed matrix.

PMID- 15247475
TI  - Thinning and flow of Tibetan crust constrained by seismic anisotropy.
AB  - Intermediate-period Rayleigh and Love waves propagating across Tibet indicate
      marked radial anisotropy within the middle-to-lower crust, consistent with a
      thinning of the middle crust by about 30%. The anisotropy is largest in the
      western part of the plateau, where moment tensors of earthquakes indicate active
      crustal thinning. The preferred orientation of mica crystals resulting from the
      crustal thinning can account for the observed anisotropy. The middle-to-lower
      crust of Tibet appears to have thinned more than the upper crust, consistent with
      deformation of a mechanically weak layer that flows as if confined to a channel.

PMID- 15247476
TI  - InSAR observations of low slip rates on the major faults of western Tibet.
AB  - Two contrasting views of the active deformation of Asia dominate the debate about
      how continents deform: (i) The deformation is primarily localized on major faults
      separating crustal blocks or (ii) deformation is distributed throughout the
      continental lithosphere. In the first model, western Tibet is being extruded
      eastward between the major faults bounding the region. Surface displacement
      measurements across the western Tibetan plateau using satellite radar
      interferometry (InSAR) indicate that slip rates on the Karakoram and Altyn Tagh
      faults are lower than would be expected for the extrusion model and suggest a
      significant amount of internal deformation in Tibet.

PMID- 15247477
TI  - Derivatives of erythropoietin that are tissue protective but not erythropoietic.
AB  - Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively
      through interaction with different receptors. We generated receptor subtype
      selective ligands allowing the separation of EPO's bioactivities at the cellular
      level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind
      to the classical EPO receptor (EPOR) and did not show any hematopoietic activity
      in human cell signaling assays or upon chronic dosing in different animal
      species. Nevertheless, CEPO and various nonhematopoietic mutants were
      cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord
      compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis
      at a potency and efficacy comparable to EPO.

PMID- 15247478
TI  - Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase
      activity.
AB  - Numerous degenerative disorders are associated with elevated levels of
      prooxidants and declines in mitochondrial aconitase activity. Deficiency in the
      mitochondrial iron-binding protein frataxin results in diminished activity of
      various mitochondrial iron-sulfur proteins including aconitase. We found that
      aconitase can undergo reversible citrate-dependent modulation in activity in
      response to pro-oxidants. Frataxin interacted with aconitase in a citrate
      dependent fashion, reduced the level of oxidant-induced inactivation, and
      converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the
      protein. Thus, frataxin is an iron chaperone protein that protects the aconitase
      [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.

PMID- 15247479
TI  - The radical site in chlamydial ribonucleotide reductase defines a new R2
      subclass.
AB  - Ribonucleotide reductase (RNR) synthesizes the deoxyribonucleotides for DNA
      synthesis. The R2 protein of normal class I ribonucleotide reductases contains a
      diiron site that produces a stable tyrosyl free radical, essential for enzymatic
      activity. Structural and electron paramagnetic resonance studies of R2 from
      Chlamydia trachomatis reveal a protein lacking a tyrosyl radical site. Instead,
      the protein yields an iron-coupled radical upon reconstitution. The coordinating
      structure of the diiron site is similar to that of diiron oxidases/monoxygenases
      and supports a role for this radical in the RNR mechanism. The specific ligand
      pattern in the C. trachomatis R2 metal site characterizes a new group of R2
      proteins that so far has been found in eight organisms, three of which are human
      pathogens.

PMID- 15247480
TI  - Thymic origin of intestinal alphabeta T cells revealed by fate mapping of
      RORgammat+ cells.
AB  - Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in
      host mucosal immunity and, unlike other T cells, have been proposed to
      differentiate from local precursors rather than from thymocytes. We show here
      that IELs expressing the alphabeta T cell receptor are derived from precursors
      that express RORgammat, an orphan nuclear hormone receptor detected only in
      immature CD4+CD8+ thymocytes, fetal lymphoid tissue-inducer (LTi) cells, and LTi
      like cells in cryptopatches within the adult intestinal lamina propria. Using
      cell fate mapping, we found that all intestinal alphabeta T cells are progeny of
      CD4+CD8+ thymocytes, indicating that the adult intestine is not a significant
      site for alphabeta T cell development. Our results suggest that intestinal
      RORgammat+ cells are local organizers of mucosal lymphoid tissue.

PMID- 15247481
TI  - Diversification of Ig superfamily genes in an invertebrate.
AB  - The freshwater snail Biomphalaria glabrata possesses a diverse family of
      fibrinogen-related proteins (FREPs), hemolymph polypeptides that consist of one
      or two amino-terminal immunoglobulin superfamily (IgSF) domains and a carboxyl
      terminal fibrinogen domain. Here, we show that the IgSF1 domain of the FREP3
      subfamily is diversified at the genomic level at higher rates than those recorded
      for control genes. All sequence variants are derived from a small set of nine
      source sequences by point mutation and recombinatorial processes. Diverse FREP3
      transcripts are also produced. We hypothesize a mechanism present in snails that
      is capable of diversifying molecules involved in internal defense.

PMID- 15247482
TI  - Cyclic AMP-induced repair of zebrafish spinal circuits.
AB  - Neurons in the human central nervous system (CNS) are unable to regenerate, as a
      result of both an inhibitory environment and their inherent inability to regrow.
      In contrast, the CNS environment in fish is permissive for growth, yet some
      neurons still cannot regenerate. Fish thus offer an opportunity to study
      molecules that might surmount the intrinsic limitations they share with mammals,
      without the complication of an inhibitory environment. We show by in vivo imaging
      in zebrafish that post-injury application of cyclic adenosine monophosphate can
      transform severed CNS neurons into ones that regenerate and restore function,
      thus overcoming intrinsic limitations to regeneration in a vertebrate.

PMID- 15247483
TI  - Cognitive control signals for neural prosthetics.
AB  - Recent development of neural prosthetics for assisting paralyzed patients has
      focused on decoding intended hand trajectories from motor cortical neurons and
      using this signal to control external devices. In this study, higher level
      signals related to the goals of movements were decoded from three monkeys and
      used to position cursors on a computer screen without the animals emitting any
      behavior. Their performance in this task improved over a period of weeks.
      Expected value signals related to fluid preference, the expected magnitude, or
      probability of reward were decoded simultaneously with the intended goal. For
      neural prosthetic applications, the goal signals can be used to operate
      computers, robots, and vehicles, whereas the expected value signals can be used
      to continuously monitor a paralyzed patient's preferences and motivation.

PMID- 15247486
TI  - Proteoglycans as cues for axonal guidance in formation of retinotectal or
      retinocollicular projections.
AB  - Understanding the formation of neuronal circuits has long been one of the basic
      problems in developmental neurobiology. Projections from the retina to their
      higher center, the optic tectum in nonmammalian vertebrates and the superior
      colliculus in mammals, are most amenable to experimental approaches; thus, much
      information has been accumulated about the mechanisms of axonal guidance. The
      retinal axons navigate along the appropriate pathway with the help of a series of
      guidance cues. Although much of the work has focused on proteinaceous factors,
      proteoglycans have been identified as playing important roles in retinal axon
      guidance. Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are
      involved in essential decisions of axon steering along the pathway. However, it
      has not been determined whether diversity of the carbohydrate chains results in
      differential effects and how their diversity is recognized by growth cones, which
      represent an important area of future research.

PMID- 15247487
TI  - The role of BETA2/NeuroD1 in the development of the nervous system.
AB  - BETA2/NeuroD1 is a member of the basic helix-loop-helix (bHLH) transcription
      factor family, which has been shown to play a major role in development of the
      nervous system and formation of the endocrine system. Gain-of-function studies
      have indicated that BETA2/NeuroD1 is important for the neurogenesis of Xenopus
      embryos and several neurogenic cell lines. Disruption of the gene encoding
      BETA2/NeuroD1 leads to severe abnormalities of the developing mouse central
      nervous system as well as the peripheral nervous system. The focus of this
      article is on the recent progress in understanding the role of BETA2/NeuroD1 in
      the development of the nervous system.

PMID- 15247485
TI  - Neurobiology of alpha-synuclein.
AB  - Alpha-synuclein is an abundant neuronal protein that has been linked both to
      normal synaptic function and to neurodegeneration. Most significantly, mutations
      in the gene encoding for alpha-synuclein are responsible for Parkinson's disease
      (PD) in rare familial cases, and the aggregated protein is a major component of
      Lewy bodies found in sporadic PD. Here we review recent data regarding the
      structure, the regulation at the transcriptional and posttranslational level, and
      the physiologic and aberrant functions of alpha-synuclein. We focus in particular
      on the fibrilization potential of alpha-synuclein and on its link with defects in
      protein degradation.

PMID- 15247488
TI  - Neural stem cells redefined: a FACS perspective.
AB  - Using the generally accepted ontogenetic definition, neural stem cells (NSCs) are
      characterized as undifferentiated cells originating from the neuroectoderm that
      have the capacity both to perpetually self-renew without differentiating and to
      generate multiple types of lineage-restricted progenitors (LRP). LRPs can
      themselves undergo limited self-renewal, then ultimately differentiate into
      highly specialized cells that compose the nervous system. However, this
      physiologically delimited definition of NSCs has been increasingly blurred in the
      current state of the field, as the great majority of studies have retrospectively
      inferred the existence of NSCs based on their deferred functional capability
      rather than prospectively identifying the actual cells that created the outcome.
      Further complicating the matter is the use of a wide variety of neuroepithelial
      or neurosphere preparations as a source of putative NSCs, without due
      consideration that these preparations are themselves composed of heterogeneous
      populations of both NSCs and LRPs. This article focuses on recent attempts using
      FACS strategies to prospectively isolate NSCs from different types of LRPs as
      they appear in vivo and reveals the contrasting differences among these
      populations at molecular, phenotypic, and functional levels. Thus, the strategies
      presented here provide a framework for more precise studies of NSC and LRP cell
      biology in the future.

PMID- 15247491
TI  - RACE using only a gene-specific primer: application of a template-switching
      model.
AB  - This article describes a simple method for accurate rapid amplification of
      complementary deoxyribonucleic acid (cDNA) ends (RACE), the distinctive feature
      being that only a gene-specific primer is used, without an anchor or adapter
      primer. Under these conditions, Thermus aquaticus (Taq) polymerase synthesizes
      cDNA ends exactly, so that amplified products obtain a characteristic structure:
      a terminal inverted repeat composed of a gene-specific primer and occasionally
      several nucleotides from its 3' flanking sequence. These structures suggest a
      hypothetical mechanism of cDNA end synthesis in which Taq DNA polymerase
      synthesizes a sequence complementary to the gene-specific primer at the 3' end of
      the daughter strand by switching the template to the 5' terminal region through
      circularization of the DNA. As a result, the targeted cDNA will be efficiently
      amplified with only a single gene-specific primer. This technique, which provides
      highly specific amplification of the 5' and 3' ends of a cDNA, is especially
      useful for isolation of cDNA when the corresponding messenger ribonucleic acid is
      scarce.

PMID- 15247489
TI  - Perspectives on MAO-B in aging and neurological disease: where do we go from
      here?
AB  - The catecholamine-oxidizing enzyme monoamine oxidase-B (MAO-B) has been
      hypothesized to be an important determining factor in the etiology of both normal
      aging and age-related neurological disorders such as Parkinson's disease (PD).
      Catalysis of substrate by the enzyme produces H2O2 which is a primary originator
      of oxidative stress which in turn can lead to cellular damage. MAO-B increases
      with age as does predisposition towards PD which has also been linked to
      increased oxidative stress. Inhibition of MAO-B, along with supplementation of
      lost dopamine via L-DOPA, is one of the major antiparkinsonian therapies
      currently in use. In this review, we address several factors contributing to a
      possible role for MAO-B in normal brain aging and neurological disease and also
      discuss the use of MAO-B inhibitors as drug therapy for these conditions.

PMID- 15247492
TI  - Double-step PCR assay to quantify Epstein-Barr viral load in peripheral blood.
AB  - Posttransplant lymphoproliferative disorders (PTLD) are a severe complication
      arising in solid organ transplant patients. A strong correlation between Epstein
      Barr virus (EBV) infection, the grade and type of immunosuppression, and the
      development of PTLD has been recognized. This article describes the development
      of a double-step polymerase chain reaction (PCR) assay for the quantification of
      EBV-deoxyribonucleic acid (DNA) to monitor EBV infection. Screening of samples
      containing >/=10(3) viral genomes/10(5) peripheral blood mononuclear cells (PBMC)
      or 100 micro L serum by a semiquantitative PCR assay is followed by
      quantification of the samples containing a high number of viral genomes in a
      quantitative-competitive (QC)-PCR assay. Screening by semiquantitative PCR
      selects samples with a high number of viral genomes for use in the more labor
      intensive and expensive QC-PCR assay and thus provides a handy means for
      quantitative DNA analysis of large numbers of samples. Our double-step PCR assay
      can be employed in EBV viral load measurement in PBMC and serum samples to
      monitor transplanted patients at risk to develop PTLD.

PMID- 15247490
TI  - Transcriptional regulation by cAMP and Ca2+ links the Na+/Ca2+ exchanger 3 to
      memory and sensory pathways.
AB  - The signaling cascades triggered by neurotrophins such as BDNF and by several
      neurotransmitters and hormones lead to the rapid induction of gene transcription
      by increasing the intracellular concentration of cAMP and Ca2+. This review
      examines the mechanisms by which these second messengers control transcriptional
      initiation at CRE promoters via transcription factor CREB, as well as at DRE
      sites via transcriptional repressor DREAM. The regulation of the SLC8A3 gene
      encoding the Na+/Ca2+ exchanger 3 (NCX3) is taken as an example to illustrate
      both mechanisms since it includes a CRE site in the promoter and several DRE
      sites in the exon 1 sequence. The upregulation of the NCX3 by Ca2+ signals may be
      specifically required to establish the Ca2+ balance that regulates several
      physiological and pathological processes in neurons. The regulatory features and
      the expression pattern of SLC8A3 gene suggest that NCX3 activity could be crucial
      in neuronal functions such as memory formation and sensory processing.

PMID- 15247493
TI  - Global analysis of gene expression by differential display: a mathematical model.
AB  - Differential display (DD) is one of the most commonly used approaches for
      identifying differentially expressed genes. However, there has been lack of an
      accurate guidance on how many DD polymerase chain reaction (PCR) primer
      combinations are needed to display most of the genes expressed in a eukaryotic
      cell. This study critically evaluated the gene coverage by DD as a function of
      the number of arbitrary primers, the number of 3' bases of an arbitrary primer
      required to completely match an mRNA target sequence, the additional 5' base
      match(s) of arbitrary primers in first-strand cDNA recognition, and the length of
      mRNA tails being analyzed. The resulting new DD mathematical model predicts that
      80 to 160 arbitrary 13mers, when used in combinations with 3 one-base anchored
      oligo-dT primers, would allow any given mRNA within a eukaryotic cell to be
      detected with a 74% to 93% probability, respectively. The prediction was
      supported by both computer simulation of the DD process and experimental data
      from a comprehensive fluorescent DD screening for target genes of tumor
      suppressor p53. Thus, this work provides a theoretical foundation upon which
      global analysis of gene expression by DD can be pursued.

PMID- 15247494
TI  - Does extraction of DNA and RNA by magnetic fishing work for diverse plant
      species?
AB  - An automated nucleic acid extraction procedure with magnetic particles originally
      designed for isolation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)
      from animal tissues was tested for plant material. We isolated genomic DNA and
      total RNA from taxonomically diverse plant species representing conifers (Scots
      pine), broad-leaved trees (silver birch and hybrid aspen), dwarf shrubs
      (bilberry), and both monocotyledonous (regal lily) and dicotyledonous (Saint
      John's wort, round-leaved sundew, and tobacco) herbaceous plants. Buffers
      developed for DNA extraction were successfully used in addition to manufacturer's
      extraction kits. The quality of RNA was appropriate for many applications, but
      the quality of DNA was not always sufficient for polymerase chain reaction (PCR)
      amplification. However, we could strikingly improve the quality by eliminating
      the adherent compounds during the extraction or later in the PCR phase. Our
      results show that the use of the procedure could be extended to diverse plant
      species. This procedure is especially suitable for small sample sizes and for
      simultaneous processing of many samples enabling large-scale plant applications
      in population genetics, or in the screening of putative transgenic plants.

PMID- 15247495
TI  - Therapeutic uses of antioxidant liposomes.
AB  - This review will focus on the therapeutic uses of antioxidant liposomes.
      Antioxidant liposomes have a unique ability to deliver both lipid- and water
      soluble antioxidants to tissues. This review will detail the varieties of
      antioxidants which have been incorporated into liposomes, their modes of
      administration, and the clinical conditions in which antioxidant liposomes could
      play an important therapeutic role. Antioxidant liposomes should be particularly
      useful for treating diseases or conditions in which oxidative stress plays a
      significant pathophysiological role because this technology has been shown to
      suppress oxidative stress. These diseases and conditions include cancer, trauma,
      irradiation, retinotherapy or prematurity, respiratory distress syndrome,
      chemical weapon exposure, and pulmonary infections.

PMID- 15247497
TI  - Complementary DNA libraries: an overview.
AB  - The generation of complete and full-length cDNA libraries for potential
      functional assays of specific gene sequences is essential for most molecules in
      biotechnology and biomedical research. The field of cDNA library generation has
      changed rapidly in the past 10 yr. This review presents an overview of the method
      available for the basic information of generating cDNA libraries, including the
      definition of the cDNA library, different kinds of cDNA libraries, difference
      between methods for cDNA library generation using conventional approaches and a
      novel strategy, and the quality of cDNA libraries. It is anticipated that the
      high-quality cDNA libraries so generated would facilitate studies involving
      genechips and the microarray, differential display, subtractive hybridization,
      gene cloning, and peptide library generation.

PMID- 15247496
TI  - Biomedical and agricultural applications of animal transgenesis.
AB  - Additive transgenesis by pronuclear injection of the mouse zygote has been in use
      for more than 20 yr and gene targeting in mouse embryonic stem cells for almost
      as long. Together, these techniques have revolutionized animal biology by helping
      to unravel much of what we now know about gene function. Both additive
      transgenics and targeting can also be performed in livestock species but the
      impact has not yet been substantial. In part, this has been the result of the
      inefficiency of the techniques but-at least in agriculture-also to a lack of
      obvious practicality. This review assesses the extent to which this situation is
      changing, with particular reference to applications in biopharming,
      xenotransplantation, and large animal models.

PMID- 15247498
TI  - The IUBMB-endorsed transporter classification system.
AB  - We here describe the transporter classification (TC) system that provides a
      rational means of classifying all transmembrane transport systems found in living
      organisms. The availability of this system provides a framework for the use of
      bioinformatic technologies to answer fundamental questions about the functions,
      mechanisms, and evolutionary pathways taken for the appearance of these systems.
      Such advances are discussed.

PMID- 15247499
TI  - Meaning-making in the immune system.
AB  - Meaning-making is the process by which a system responds to an indeterminate
      signal. This article focuses on meaning-making in living systems. It proposes
      several guidelines for studying the process of meaning-making in living systems
      in general, and in the immune system in particular. Drawing on a general
      framework for studying meaning-making in living systems, I suggest three basic
      organizing concepts for studying meaning-making-variability of the signal,
      context markers, and transgradience. Those concepts present a radical alternative
      to the information-processing approach that governs biological research and may
      shed new light on biological processes.

PMID- 15247500
TI  - The placebo response: its putative role as a functional salutogenic mechanism of
      the central nervous system.
AB  - The concept of placebo has evolved over time. Generally believed to be the basis
      of the premodern pharmacopoeia, the placebo has been adopted in practice as a
      harmless but unscientific approach towards alleviating symptoms. Currently, many
      medical scientists view placebos pejoratively as confounding elements in the
      analysis of randomized control trials.This article examines the changing
      attitudes towards placebos and the persistent controversies that surround their
      administration. The possible role of the placebo response as a functional
      salutogenic brain mechanism is considered, and elements of Edelman's
      neurobiological model of self and attractor theory are combined to explain how a
      unitary response by the central nervous system might yield diverse placebo
      effects. It is concluded that placebo responses are rooted in the complexity of
      mind/body interactions and that their underlying physiological mechanisms may be
      elucidated via methods that directly examine brain activity as the basis of
      subjective experience.

PMID- 15247501
TI  - The sculpturing role of fibroblast-like cells in morphogenesis.
AB  - Cells of multicellular organisms are semi-fluid creatures. Even when they form
      specific cell-cell adhesions, they cannot create a defined shape or a tissue
      specific architecture. Cartilaginous organs, such as ears and noses, exemplify
      the fact that form is imprinted in the extracellular matrix (ECM), which leads to
      the conclusion that cells must have the ability to shape the ECM in which they
      reside. This seems to be true for most tissues. The role of the ECM as an
      integrator of cells into functional assemblies with defined architecture is
      unique to multicellular organisms. The evolution of multicellularity became
      possible as a consequence of cells acquiring two new properties: first, cell
      surface macromolecular complexes that function in cell-cell binding; and, second,
      an ECM that integrates cells into three-dimensional structures. These two new
      properties allowed the evolution of the two basic types of cells-epithelial and
      mesenchymal. The appearance of the latter, a fibroblast-like cell with abundant
      filopodia, enabled the sculpturing of the ECM and the formation of complex tissue
      specific architectures.

PMID- 15247502
TI  - Does biomedicine entail the successful reduction of pathology to biology?
AB  - The idea of reducing pathology to biology has an extensive history, and the
      initial forms of the enterprise were unsuccessful. This article discusses the
      philosophical literature surrounding the notion of reduction in the sciences in
      general and of biology in particular; reviews several 19th-century programs that
      promoted the reduction of medicine to other biological disciplines; and examines
      the post-war origins of the notion of biomedicine. It shows how biology and
      medicine tend to interact in the constitution of new biomedical knowledge and how
      the notion of a pathological process resulting in a lesion remains central to the
      understanding of disease. The article proposes that while strict reduction has
      yet to be realized, one can speak of a continuing and successful realignment of
      biology and pathology since the Second World War.

PMID- 15247503
TI  - Moving beyond bioethics: history and the search for medical humanism.
AB  - From both within and without bioethics, growing criticism of the predominant
      methods and practices of the field can be heard. These critiques tend to lament
      an emphasis on logically derived rules and philosophical theories that
      inadequately capture how and why people have the moral attitudes they do, and
      they urge the use of more empirically grounded social sciences--history,
      sociology, and anthropology--to draw attention to the complex factors behind such
      attitudes. However, these critiques do not go far enough, as they do not question
      why debate over ethical categories should have such a central role in voicing
      concerns about medicine. The importance of using other forms of inquiry,
      especially that of history, to examine aspects of medical practice and the
      emergence of bioethics itself is not simply to refine bioethical moral analysis.
      Instead, history can be employed to counter the preoccupation with translating
      concerns about medicine into moral terms and to move towards what is more sorely
      needed: a true medical humanism.

PMID- 15247504
TI  - Conceptualizing "religion": How language shapes and constrains knowledge in the
      study of religion and health.
AB  - Despite recent advances in the field of religion and health, meaningful findings
      will increasingly depend on the capacity to conceptualize "religion" properly. To
      date, scientists' conception of religion has been shaped by the Enlightenment
      paradigm. However, recent developments in philosophy make the "objectivity" of
      the Enlightenment paradigm problematic, if not untenable. Contrary to common
      understanding, the secularism essential to the Enlightenment paradigm does not
      enjoy any special privilege over religious ways of seeing the world, because both
      religious and secular worldviews constitute self-referentially complete
      interpretations of the human condition. If there is no objective frame of
      reference from which to measure religiousness, then the study of religion and
      health is fundamentally contingent on the specific languages and contexts in
      which particular religions find expression. While applying this cultural
      linguistic approach to religion would require significant changes in the existing
      methods for studying religion and health, such changes may generate a deeper
      understanding of this relationship.

PMID- 15247505
TI  - Bodies and borders: a new cultural history of medicine.
AB  - Both medicine and the history of medicine have seen many changes in the last four
      decades. The way we tell the story of medical developments no longer concentrates
      on the important doctors and their ideas. The influences of social history in the
      1960s and 1970s and cultural history in the 1980s and 1990s have broadened and
      enriched the interpretations of our medical past. The social historians have
      helped us to include politics, economics, and the leading ideas of any period we
      wanted to study; the cultural approach has added ethnography as well as an
      emphasis on language or discourse. Today there is a new history of medicine, one
      far more willing to cross disciplinary boundaries to ask questions about how we
      know what we know and why we do what we do. This article highlights some of the
      work in the adjoining fields of medical anthropology and of literature and
      medicine to demonstrate new interests, new questions, and new methods of inquiry.
      However, although we have cast our nets far more widely in the process of
      professionalizing the history of medicine, there is a question about whether we
      have lost the appeal to one of our core constituencies: medical students and
      physicians. We need to welcome some of the new changes in medical history as in
      medicine itself; the common goal is to achieve a better understanding of what we
      have done and what we are doing.

PMID- 15247506
TI  - Superficial? Not us--we men are born molecular geneticists!

PMID- 15247507
TI  - Genetics: the not-so-new new thing.
AB  - Practical knowledge of heredity predates history. Indigenous peoples laid the
      foundations of modern agriculture by developing plants such as corn. However, the
      language and metaphors of the Human Genome Project treat modern genetics as if it
      had no historical antecedents and fail to acknowledge these early contributions
      to the science of heredity. The results of this blindness are twofold: it
      exacerbates reluctance of native peoples to take part in genetic research and to
      garner the benefits of genetic medicine, and it encourages "biopiracy," as modern
      scientists "discover" and patent native plants.

PMID- 15247509
TI  - Family medicine: its core principles and impact on patient care and medical
      education in the United States.
AB  - The specialty of family medicine arose out of a combination of American public
      and professional concerns regarding fragmentation of health care and was intended
      to foster a type of physician with a scope of clinical competence that would
      allow the patient, not the disease, to be the focus. Family physicians serve as
      the patient's personal physician and provide entry to the health care system,
      provide comprehensive care, maintain continuing responsibility for the patient
      including necessary coordination of care and referral, and provide care
      appropriate to the patient's physical, emotional, and social needs in the context
      of family and community. The specialty is currently second only to internal
      medicine in size, and makes a significant contribution to patient care and
      medical education. As family medicine looks to the future, some of its challenges
      include continuing to attract medical students to the specialty, refine research
      themes, and gain further acceptance in academic medical centers.

PMID- 15247510
TI  - Transcriptional profiling of the scleroderma fibroblast reveals a potential role
      for connective tissue growth factor (CTGF) in pathological fibrosis.
AB  - The cause of fibrotic disease is unknown. We have undertaken transcriptional
      profiling of dermal fibroblasts cultured from patients with the fibrotic disease
      scleroderma (systemic sclerosis, SSc) to identify genes overexpressed in fibrosis
      and have explored their contribution to the fibrotic phenotype. Connective tissue
      growth factor (CTGF, CCN2), a member of the CCN family of proteins, is
      overexpressed in SSc fibroblasts. In adult skin, CTGF is not normally expressed
      in dermal fibroblasts. However, CTGF is induced during the wound healing response
      and is constitutively overexpressed by fibroblasts present in fibrotic lesions.
      The overexpression of CTGF present in fibrotic lesions contributes to the
      phenotype of scleroderma in that CTGF promotes matrix deposition, and fibroblast
      adhesion and proliferation. In animal models, whereas either TGF beta or CTGF
      alone produce only a transient fibrotic response, CTGF and TGF beta act together
      to promote sustained fibrosis. Thus the constitutive overexpression of CTGF by
      fibroblasts present in fibrotic lesions would be expected to directly contribute
      to chronic, persistent fibrosis.

PMID- 15247511
TI  - Osteoclasts, mononuclear phagocytes, and c-Fos: new insight into osteoimmunology.
AB  - Osteoimmunology is the emerging concept that certain molecules link the skeletal
      and immune systems. The transcription factor c-Fos, a component of activator
      protein-1 (AP-1), is essential for osteoclast differentiation. Mice lacking c-Fos
      are osteopetrotic owing to impaired osteoclast development. Recent studies
      suggest that in contrast to this positive role in osteoclastogenesis, c-Fos
      expression inhibits differentiation and activation of mononuclear phagocytes.
      Here, we focus on the contrasting roles of c-Fos in the bone and immune lineages.
      Both osteoclasts and mononuclear phagocytes are derived from common myeloid
      precursors. Osteoclasts resorb bone, whereas macrophages and myeloid dendritic
      cells phagocytose microbial pathogens, initiating innate and adaptive immunity.
      Differentiation of the common precursors into either bone or immune lineage is
      determined by ligand binding to cell-surface receptors, particularly receptor
      activator of NF-kappa B (RANK) for osteoclasts, or Toll-like receptors (TLRs) for
      mononuclear phagocytes. Both RANK and TLRs activate the dimeric transcription
      factors NF-kappa B and AP-1. Yet, c-Fos/AP-1 plays a positive role in osteoclasts
      but a negative role in macrophages and dendritic cells. Further study is
      necessary to clarify this dual role of c-Fos.

PMID- 15247512
TI  - Efficacy of training program for ambulatory competence in elderly women.
AB  - The optimal prevention of osteoporotic fractures in the elderly consists of
      increasing the bone density and preventing falls. We report on the efficacy of
      training program to promote ambulatory competence in elderly women. Twenty-five
      elderly women were enrolled in our training program, which is a three-month
      program consisting of dynamic balance training with Galileo 900 (Novotec,
      Pforzheim, Germany) once a week, combined with daily static balance (standing on
      one leg like a flamingo) and resistance (half-squat) training. The mean age of
      the participants was 72.8 years (range, 61-86 years). After 3 months of training,
      the step length, knee extensor muscle strength, and maximum standing time on one
      leg were significantly increased, while the walking speed and hip flexor muscle
      strength were not significantly altered. During the study period, no serious
      adverse events such as new vertebral fractures or adverse cardiovascular symptoms
      were observed in any participant. The present preliminary study shows that our
      training program may have the potential to promote ambulatory competence in
      elderly women.

PMID- 15247513
TI  - Expression profiling in hepatocellular carcinoma with intrahepatic metastasis:
      identification of high-mobility group I(Y) protein as a molecular marker of
      hepatocellular carcinoma metastasis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and aggressive human
      malignancies. Its high mortality rate is mainly a result of intra-hepatic
      metastases. To investigate the detailed genetic mechanisms in cancer metastasis,
      we compared the expression profiles of 20 HCCs with intrahepatic metastasis and
      10 HCCs without intrahepatic metastasis using an oligonucleotide array. Of the
      approximately 12,600 genes that were analyzed, we identified 34 genes whose
      expression levels were significantly correlated with intrahepatic metastasis
      (P<0:05). Of these genes, we further investigated the expression of high-mobility
      group I(Y) [HMG-I(Y)] protein. Real-time quantitative reverse transcription
      polymerase chain reaction (RT-PCR) confirmed that HMG-I(Y) was upregulated in HCC
      with intrahepatic metastasis, compared to its level in HCC without intrahepatic
      metastasis. Further immunohistochemical examination of HMG-I(Y) revealed a
      significant overexpression in HCC with intrahepatic metastasis, compared with
      that in HCC without intrahepatic metastasis (P<0:05). These results indicate that
      the molecular signatures of HCC with intrahepatic metastasis and of HCC without
      intrahepatic metastasis are clearly different. HMG-I(Y) expression was associated
      with intrahepatic metastasis and may be a predictive marker of HCC intrahepatic
      metastasis.

PMID- 15247514
TI  - Association of food location with biological cues in the macaque monkey.
AB  - Many animal species including humans are endowed with the ability to use
      biological cues and can extract information by observing other individuals. This
      study explored whether the macaque monkey could use biological cue to find a
      hidden target. When the experimenter hid food in one hand and crossed and
      uncrossed hands quickly, the monkey had no difficulty in finding the food and
      correctly reached for the baited hand. However, when the food was hidden in one
      of two cups and the cups were shuffled, the monkey could correctly select the
      baited cup only at an equal level of luck. These results indicate that the
      macaque monkey could associate the location of food with a biological cue better
      than a non-biological cue and keep it in memory when the target was unseen.

PMID- 15247515
TI  - A 73-year-old man with confusion, fever, and positive MPO-ANCA.
AB  - A 73-year-old man was admitted to the hospital because of progressive lethargy
      and fever. He had a history of hypertension since the age of 40, and was
      diagnosed as having a testicular tumor at the age of 50. On admission, he looked
      pale and stuporous. Laboratory examination revealed microscopic hematuria. The
      erythrocyte sedimentation rate was 110 mm/hr, and the serum CRP was 14.3 mg/dl.
      The titer of myeloperoxidase-antineutrophilic cytoplasmic antibodies (MPO-ANCA)
      was higher than 1:1000. On the sixth hospital day, he required ventilatory
      assistance because of aspiration pneumonia and was connected to a respirator. He
      was treated with intravenous corticosteroids, to which he responded in the short
      term with resolution of the fever and decrease in the serum CRP level, however,
      the consciousness disturbance persisted and the fever recurred soon thereafter.
      He developed gross hematuria and the renal function deteriorated. He eventually
      died of renal failure and pulmonary hemorrhage. Although his clinical course and
      laboratory findings were consistent with those of microscopic polyangitis, the
      pathological diagnosis was crescentic glomerulonephritis with no evidence of
      vasculitis.

PMID- 15247516
TI  - [Regulation of mast cell survival and activation by monomeric IgE].

PMID- 15247517
TI  - [Rationale and practice for the treatment of allergic diseases in childhood].

PMID- 15247518
TI  - [Studies on airway hyperresponsiveness by the Astograph(r) method in asthmatics
      and young adult non-asthmatic asymptomatics].
AB  - We investigated airway hyperresponsiveness (AHR) by the continuous inhalation
      method using an Astograph(R) in 105 asthmatics and 141 non-asthmatic
      asymptomatics. The range of Dmin (1 U=one minute inhalation of 1 mg/ml of
      methacholine) of asthmatics was 0.001 to 28.70 U, and that of adjusted Dmin of
      non-asthmatic asymptomatics was 0.28 to 190 U; thus, an apparent overlap was
      recognized in the distributions of Dmin. Ninety-five percent of asthmatics had a
      Dmin lower than 7 U, and 95% of non-asthmatic asymptomatics had a Dmin higher
      than 0.9 U. Presuming that almost all asthmatics had AHR, it was inferred that
      nearly half of non-asthmatic asymptomatics had AHR, too. Comparison with previous
      reports suggests that AHR in healthy people may be increasing generally. When
      Dmin is determined to be>7 U by the Astograph(R) method, it is likely that the
      patient does not have asthma. When a patient has a Dmin<0.9 U, it is highly
      probable that the patient has asthma.

PMID- 15247519
TI  - [A case of pneumocystis carinii pneumonia associated with low dose methotrexate
      treatment for rheumatoid arthritis and trimethoprim-sulphamethoxazole induced
      pancytopenia].
AB  - A 64-year-old man was admitted to our hospital complaining of dyspnea and fever.
      He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest
      radiography showed diffuse ground-glass attenuation in both lung fields, and
      hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on
      transbronchial lung biopsy, and the serum beta-D glucan level was high. We
      started treatment with trimethoprim-sulphamethoxazole, but respiratory failure
      worsened, and drug-induced pancytopenia occurred. Although trimethoprim
      sulphamethoxazole was stopped, pancytopenia persisted and the patient required
      ventilatory support. After we changed the medication from trimethoprim
      sulphamethoxazole to pentamidine, respiratory failure improved. It was thought
      that pneumocystis carinii pneumonia was associated with low-dose methotrexate and
      that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe
      pancytopenia.

PMID- 15247520
TI  - [Juniper pollen monitoring by Burkard sampler in Galveston, Texas, USA and
      Japanese cedar pollen counting in Fukuoka, Japan -- introduction of Pan American
      Aerobiology Association protocol counting technique].
AB  - We have monitored Juniper pollen which caused winter allergy symptoms by Burkard
      sampler in Galveston, Texas. We identified and counted Juniper pollen grains by
      PAAA protocol which was a comprehensive guideline for the operation of Hirst-Type
      suction bioaerosol sampler, (original of Burkard sampler) in the USA. In
      Galveston we were able to detect the Mountain Cedar (Juniperus ashei) pollen from
      December to of January, and Eastern Red Cedar (Juniperus virginiana) which has
      cross reactivity to MC from almost middle of January to February. There is no MC
      vegetation in Galveston. We found the pollen grains were transported from west at
      Edward Plateau in West Texas where it was thickly wooded. Then, we tried to
      monitor Japanese Cedar (JC) pollen grains in Fukuoka, Japan according with the
      same method. We found the significant positive correlation between the pollen
      counts using one single longitudinal traverse counting technique in the PAAA
      protocol and the JC pollen counting on the whole of Melinex tape per 24 hours
      (R2=0.9212, p=0.0001), and the gravitational method that is Durham sampler's
      pollen counting in 2002 (R2=0.489, p=0.0001), and in 2003 (R2=0.948, p=0.0001)
      respectively. We suggested that we can use the PAAA protocol for airborne pollen
      investigation in Japan by Burkard sampler.

PMID- 15247521
TI  - [Willingness to pay for Japanese cedar pollinosis: comparison between pollination
      and non-pollination seasons].
AB  - Allergic rhinitis is not fatal illness, but its high prevalence and several
      symptoms result in substantial medical cost. There is increasing interest in the
      use of economic evaluations in healthcare; therefore, we investigated patients'
      willingness to pay (WTP) for prevention and cure from Japanese cedar pollinosis
      (JCP), and compared WTP values assessed in non-pollination season (June 1998) and
      pollination season (February-March 2003). Japanese economic woes got worse in
      2003 than in 1998. Patients were randomly selected from ENT clinical sites in
      Osaka, 175 and 645 patients completed WTP questionnaire in 1998 and 2003,
      respectively. WTP value was lower in 2003 than in 1998, which related to part
      time employees and housewives' reducing WTP. Declining WTP value did not
      associated with the differences in patient characteristics between 1998 and 2003
      including age, duration of disease, nasal symptom severity and comorbid
      condition. These results show that we have to take employment status into account
      in economic evaluations. Decline in WTP for JCP in 2003 was strongly affected by
      Japanese sluggish economy, and the WTP seemed to be stable value in individual
      patients.

PMID- 15247522
TI  - [Treatment of Japanese cedar pollinosis and its impact on patient satisfaction].
AB  - Japanese cedar pollinosis is a major public health problem in Japan because of
      its severe symptom and high prevalence. However, patient satisfaction by
      treatment is poor according to current reports. As the treatments, pre-seasonal
      medication and single peroral anti-allergic drug on demand are frequently used in
      Japan. Against conventional methods, we treated 301 patients with Japanese cedar
      pollinosis by persistent use of combined drugs (topical steroid, peroral anti
      allergic drug and eye drop) without pre-seasonal medication in 2003.
      Immunotherapy was also used in 90 patients treated. As a result, 97% of patients
      was satisfied in this treatment and immunotherapy contributed to reduction in the
      amount of drug and high treatment outcome.

PMID- 15247525
TI  - [Reevaluation of hygiene theory].

PMID- 15247523
TI  - [Study of thromboxane A2 antagonist reduction in the treatment of patients with
      perennial allergic rhinitis].
AB  - We investigated whether or not we could reduce the medication for patients with
      perennial allergic rhinitis after improvement of the nasal symptoms. We
      administered the thromboxane A2 receptor antagonist Ramatroban, which also
      improves non-specific hypersensitivity, for 4 weeks and then reduced the dose to
      half for 4 weeks and investigated the severity of general symptoms and each nasal
      symptom (sneeze, rhinorrhea, and congestion). There was a significant improvement
      in the severity of general symptoms and each nasal symptom for the first 4 weeks
      (p<0.01), which was maintained for 4 weeks after reduction of the dose (n=14).
      There was no difference in the severity of symptoms between the reduced dosage
      (n=14) and the maintained dosage (n=15) groups. We also investigated the level of
      eosinophilia in nasal smears before and after the treatment (n=14) and showed
      that the level was significantly (p<0.01) reduced after the start of treatment.
      In conclusion, it was noted that we could reduce the dose of Ramatroban after the
      improvement of nasal symptoms on patients with perennial allergic rhinitis.

PMID- 15247526
TI  - [Toll-like receptor and allergy].

PMID- 15247527
TI  - [Death from asthma attacks in Tohoku District. Results from questionnaire
      surveyed from 1992 to 2001].
AB  - In Tohoku district, death from asthma attacks was surveyed from 1992 to 2001.
      After presence of death from asthma attacks during the previous year were
      confirmed by post card at the beginning of every February, details of each case
      were asked by questionnaire. In total, 299 cases (male: 186, female: 113) were
      recognized as death from asthma attacks. Middle-aged and older asthmatics over 50
      year accounted for 2/3 of the cases and the most death was recorded in asthmatics
      in the second decade of life under 50. Out-patients accounted for 78%. When they
      visited hospitals, 60% was in cardio-pulmonary arrest and 89% was in more
      critical condition than severe attacks. About duration of attacks from the onset
      to their death, within 2 hrs accounted for 25.6%, within 1 day did for 39.6%, and
      over 1 day did for 34.8%. Although the most death was found in patients whose
      duration of asthma was between 1 and 10 years, 16 cases died within 1 year from
      the onset of their asthma. About severity during the past year, 34% had severe
      asthma, 45% moderate, and 21% mild. Number of death from asthma attacks in Tohoku
      district was clearly reduced over the past 5 years. The number was reduced to
      about one-fourth of that at the beginning of survey.

PMID- 15247528
TI  - [Epidemiologic study on the prevalence of the sick house syndrome in Japan].
AB  - PURPOSE: Sick house syndrome (SHS; sick house syndrome) presents healthy damage
      owing to the indoor environment of a building. Although SHS is recognized
      socially, there is no medical definition and its illness concept is also
      ambiguous. This time, large-scale epidemiology investigation about SHS of our
      country was conducted. METHOD: The investigation paper in the "epidemiological
      research on SHS" group of the Ministry of Health, Labour and Welfare was used.
      The reply of 8737 adults and 9387 children was obtained. RESULT: By the
      definition of a disease, prevalence of SHS was 8.5 to 22.1% at the adult and 5.6
      19.8% in the child. Cause environmental substances were "a shampoo, makeup and a
      perfume", "the smell of a wall or the building materials of a floor", and
      "paint". There was no significant difference in SHS development of symptoms in
      construction years and the situation of extension and alteration of a dwelling.
      As a feature of a life style, symptoms developed in the strong group of stress
      and sensitive to a smell developed mostly. CONSIDERATION: Prevalence differed
      greatly by how SHS is defined. In order to diagnose truer SHS, we think that the
      prudent definition based also on the international standard is required.

PMID- 15247529
TI  - [Rice pollen asthma and pollinosis in childhood: seasonal asthma and allergic
      rhinoconjunctivitis during the period of rice pollen emission in the surrouding
      area of rice field].
AB  - Although in 1969, rice pollen was first reported as a cause of asthma, rice
      pollen allergy has not been studied after the first report and thus the allergic
      significance of rice pollen is not well recognized at present. We investigated
      the sensitization to various allergens and the residential areas in children with
      the symptoms of asthma or rhinoconjunctivitis during the first decade of August,
      and measured rice pollen-specific IgE antibodies. Eighty-eight children (57 boys
      and 31 girls, mean age 8.5+/-2.9 years) with bronchial asthma or allergic
      rhinitis/conjunctivitis were included in this study and divided into two groups:
      children with (n=21) or without (n=67) symptoms during this period. The
      positivity rate to orchard grass pollen and the rate of residence in the
      surrounding area of rice field were high (81%, P=0.008 and 86%, P<0.001,
      respectively) in children with allergic symptoms, as compared to the values (48%
      and 27%, respectively) in children without symptoms. As the rice pollen season in
      Nagano occurs in the first decade of August, we measured rice pollen-specific IgE
      antibodies in 8 patients with symptoms during this period; all of these patients
      showed positive IgE antibodies to rice pollen. The RAST-inhibition assay using
      orchard grass and rice pollen indicated cross-allergenecity between these two
      pollen and also the existence of rice pollen-specific allergens. These results
      suggest that rice pollen induces seasonal asthma and allergic rhinoconjunctivitis
      during the first decade of August, which is the rice pollen season, in the
      surrounding area of rice fields.

PMID- 15247530
TI  - [Comparison of the bronchodilator effect of salbutamol between pressure metered
      dosed inhaler and dry powder inhaler in patients with stable bronchial asthma].
AB  - Recently, dry powder inhaler (DPI) was more available than pressure metered dosed
      inhaler (pMDI) for the inhalation therapy of the respiratory disease. But there
      are differences in the lung deposition of the drug in these devices. We
      investigated the bronchodilator effect of salbutamol inhalation with two device,
      pMDI and Tubuhaler on the stable 8 asthmatic patients. The time course of FEV1
      had a no significant difference between two devices. DeltaAUC (=difference
      between area under the curve for time course of increase in FEV1 via pMDI and via
      DPI) and Deltamax FEV1 (=difference between maximum increases in FEV1 following
      inhalation of salbutamol via pMDI and DPI) were defined as the index of
      difference of bronchodilator effect between the two devices. PMDI was more
      effective on improving the pulmonary function in subjects with severely decreased
      FEV1 and FEV1% than DPI. These results may reflect the correlation of inspiratory
      flow rate and drug deposition. PMDI is still useful on the part of asthmatic
      patients with decreased pulmonary function.

PMID- 15247531
TI  - [Symptoms in asthmatics living in cold districts during winter].
AB  - Exposure to cold is known as a potential exacerbating factor in asthmatics.
      However, few studies have investigated severity of symptoms during daily life in
      winter for asthmatics living in northern Hokkaido, the coldest region in Japan.
      We sent questionnaires to 126 asthmatics living in northern Hokkaido, and
      obtained answers from 116 patients (52 males, 64 females). Breathing difficulties
      during cold-air exposure were reported by 62.1% of patients. Furthermore, 19.6%
      of patients had experienced the need for bronchodilators following cold-air
      induced attacks. Limitations to daily life in winter caused by exacerbated
      asthmatic symptoms were recognized by 48.3% of patients. Asthmatic exacerbation
      was experienced by 30% of patients in summer (May to August), compared to >35% in
      winter (September to April). No significant differences in results were noted
      between atopic and non-atopic patients. Improvements in respiratory symptoms
      during winter are thus necessary for better quality of life in asthmatics living
      in cold districts.

PMID- 15247532
TI  - [Analysis of facial lesions on adult type atopic dermatitis with anti-fungus drug
      (terbinafine hydrochloride) -- analysis of serum anti-Malassezia IgE antibody
      titers and histamine release test].
AB  - Malassezia furfur has been described as an aggravating factor in facial lesions
      of atopic dermatitis, and oral antifungal agents have been reported to be
      effective against these lesions. We used terbinafine hydrochloride to treat 15
      patients with adult-type atopic dermatitis and evaluated its efficacy by
      measuring the improvement in facial skin manifestations, serum IgE values, and
      serum anti-Malassezia IgE antibody titers. A histamine release test (HRT) for
      Malassezia. was also performed in 6 of the 15 patients. The facial skin
      manifestations improved in 8 (53.3%) of the 15 patients, and there were
      significant simultaneous decreases in their serum IgE values. The serum anti
      Malassezia IgE antibody titer decreased significantly in all 15 patients.
      However, no significant correlation was observed between the HRT and the facial
      skin manifestations. We concluded that oral terbinafine hydrochloride is
      effective against the facial lesions of atopic dermatitis patients and this is
      possibly caused by decrease of Malassezia antigen in the facial lesions.

PMID- 15247533
TI  - Dopamine dysregulation syndrome in Parkinson's disease.
AB  - PURPOSE OF REVIEW: Dopamine replacement therapy in Parkinson's disease
      ameliorates motor symptoms. However, it has recently been recognized that a small
      sub-group of patients suffer motor and behavioural disturbances attributable to
      taking quantities of medication well beyond the dose required to treat their
      motor disabilities. This review examines the phenomenology of dopamine
      dysregulation syndrome in relation to the current understanding of basal ganglia
      function and its impact on long-term management. RECENT FINDINGS: Cortico-striato
      thalamic circuits are implicated in the behavioural and motor disturbances
      associated with compulsive medication use in Parkinson's disease. Advances in
      understanding of the role of dopamine in psychostimulant addiction are important
      in helping to understand dopamine dysregulation. SUMMARY: Recognition of dopamine
      dysregulation syndrome and characterization of its phenomenology supports the
      notion that the medication used to treat Parkinson's disease can disrupt basal
      ganglia mediated motor and behavioural functioning. Refinement of clinical
      strategies to predict, identify and manage this syndrome will aid the future
      treatment of motor and non-motor complications of Parkinson's disease.

PMID- 15247534
TI  - Dementia in Parkinson's disease: cause and treatment.
AB  - PURPOSE OF REVIEW: Dementia in Parkinson's disease is increasingly being
      recognized. A number of studies have recently appeared on the epidemiology,
      clinical features, pathological correlations and treatment of dementia in
      Parkinson's disease. The purpose of this article is to provide an overview of
      recent findings on dementia associated with Parkinson's disease, from February
      2003 to the present. RECENT FINDINGS: The cumulative prevalence of dementia in
      Parkinson's disease can be as high as 78%; dementia is especially prevalent in
      older patients. The profile of dementia seems to be different from that of
      Alzheimer's disease and similar to that of dementia with Lewy bodies.
      Clinicopathological correlation studies have suggested that dementia correlates
      best with Lewy bodies in certain limbic and cortical areas, but not all patients
      with sufficient Lewy bodies for a pathological diagnosis of dementia with Lewy
      bodies are demented. Cholinergic deficits in the cerebral cortex can be shown
      with in-vivo imaging studies, and seem to be more severe than in Alzheimer's
      disease. Several small studies with three different cholinesterase inhibitors
      suggest that these drugs can be effective in the treatment of PD dementia.
      SUMMARY: Dementia is highly prevalent in Parkinson's disease. The prototype of
      dementia in Parkinson's disease is a dysexecutive syndrome with impaired
      attention, executive functions and secondarily impaired memory. Neurochemically
      the most significant deficit seems to be cholinergic; dementia seems to correlate
      best with cortical and limbic Lewy bodies. Preliminary evidence suggests that
      cholinesterase inhibitors may be effective in Parkinson's disease dementia, and
      the results of large-scale, randomized and controlled studies are awaited to
      confirm these findings.

PMID- 15247535
TI  - Falls in Parkinson's disease.
AB  - PURPOSE OF REVIEW: To summarize the latest insights into the clinical
      significance, assessment, pathophysiology and treatment of falls in Parkinson's
      disease. RECENT FINDINGS: Recent studies have shown that falls are common in
      Parkinson's disease, even when compared with other fall-prone populations. The
      clinical impact of falls is considerable, often leading to an incapacitating fear
      of renewed falls. The associated costs for society are substantial. Clinical
      assessment often includes the retropulsion test, and recent studies have offered
      practical recommendations regarding the execution and scoring of this test.
      Insights into the pathophysiology underlying falls are growing and point to an
      important role for the loss of inter-segmental flexibility ('stiffness'), which
      predisposes patients to falls in a backward or medial-lateral direction. New
      evidence has clarified why Parkinson's disease patients commonly fall during
      transfers and under 'dual tasking' circumstances. The absence of adequately
      directed arm movements may explain the relatively high proportion of hip
      fractures in Parkinson's disease. The importance of freezing of gait as a cause
      of falls is recognized, and we are beginning to understand the different
      manifestations of gait freezing. Recent work has defined the contributions of
      pharmacotherapy, stereotactic neurosurgery, physiotherapy and multidisciplinary
      interventions in the treatment of postural instability to prevent falls in
      Parkinson's disease. SUMMARY: No dramatic breakthroughs have occurred during the
      review period, but new information in various areas may be useful for practising
      clinicians. Interesting new questions have been raised that should fuel studies
      of pathophysiological mechanisms, which could help in the development of improved
      treatment strategies to reduce falls in Parkinson's disease.

PMID- 15247536
TI  - Olfaction and Parkinson's syndromes: its role in differential diagnosis.
AB  - PURPOSE OF REVIEW: Marked olfactory dysfunction (hyposmia) is a frequent and
      early abnormality in Parkinson's disease. We review recent advances related to
      its cause and its clinical relevance with respect to the differential diagnosis
      of Parkinsonian syndromes. RECENT FINDINGS: Marked olfactory dysfunction occurs
      in Parkinson's disease and dementia with Lewy bodies but is not found in
      progressive supranuclear palsy and corticobasal degeneration. In multiple system
      atrophy, the deficit is mild and indistinguishable from cerebellar syndromes of
      other aetiologies, including the spino-cerebllar ataxias. This is in keeping with
      evidence of cerebellar involvement in olfactory processing, which may also help
      to explain recent findings of mild olfactory dysfunction in essential tremor.
      Smell testing remains, however, a clinically relevant tool in the differential
      diagnosis of indeterminate tremors. Intact olfaction has also been reported
      recently in Parkin disease (PARK 2) and vascular Parkinsonism. The relevance of
      sniffing ability to olfaction and a possible role of increased tyrosine
      hydroxylase and dopamine in parts of the olfactory bulb are issues of current
      interest with respect to pathophysiology. The early or 'pre-clinical' detection
      of Parkinson's disease is increasingly recognized as an area in which olfactory
      testing may be of value. SUMMARY: Research findings have confirmed a role for
      olfactory testing in the differential diagnosis of movement disorders, and
      suggest that this approach is currently underused in clinical practice. Validated
      test batteries are now available that may prove to be of practical use in the
      differential diagnosis of Parkinsonian syndromes and indeterminate tremors.

PMID- 15247537
TI  - Antibasal ganglia antibodies and their relevance to movement disorders.
AB  - PURPOSE OF REVIEW: Recently, autoaggressive immunological responses were included
      among the causative agents of basal ganglia dysfunction. Autoaggressive immune
      mediated illnesses secondary to group A beta-haemolytic streptococcal infections
      present with motor and psychiatric symptoms, due to basal ganglia involvement.
      These disorders have been associated with serum antineuronal antibodies,
      relatively specific to human basal ganglia tissue. This review summarizes the
      most recent studies concerning antibasal ganglia antibodies, focusing on the
      associated phenotypes and the hypotheses concerning their pathogenicity. RECENT
      FINDINGS: The spectrum of post-streptococcal neuropsychiatric disorders
      associated with antibasal ganglia antibodies seems broader than previously
      recognized. Other than chorea, tics and obsessive-compulsive disorder, which
      constituted the bulk of previously described disorders associated with antibasal
      ganglia antibodies, post-streptococcal neuropsychiatric disturbances include a
      wider range of motor and behavioural abnormalities, in keeping with the
      multifunctional role of the basal ganglia. An encephalitis lethargica-like
      illness following streptococcal infection was reported, and unusual adult-onset
      movement disorders associated with antibasal ganglia antibodies were documented.
      Moreover, investigators provided preliminary evidence for a pathogenic role of
      autoantibodies in Sydenham's chorea, the prototypic post-streptococcal
      neuropsychiatric disorder. SUMMARY: Antibasal ganglia antibodies are relatively
      specific in identifying post-streptococcal neuropsychiatric disorders, which
      constitute a wider spectrum of movement disorders than previously recognized.
      Although their sensitivity in diagnosing Sydenham's chorea seems excellent, it is
      not yet possible to extrapolate this sensitivity to all the recently identified
      post-streptococcal neuropsychiatric disorders. The antigens targeted by these
      autoantibodies and their pathogenic importance are currently under investigation.
      Preliminary evidence suggests that antibasal ganglia antibodies may be
      pathogenic.

PMID- 15247538
TI  - Chorea: non-genetic causes.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the literature on the non
      genetic causes of chorea. The differential diagnosis of the large number of
      causes of sporadic chorea is often a challenging task. Interest has also been
      growing in the possibility that the mechanism responsible for Sydenham's chorea
      plays a role in the pathogeneis of other neuropsychiatric disorders. RECENT
      FINDINGS: Stroke is the main cause of sporadic chorea. Sydenham's chorea shares
      clinical features with tic disorders, such as obsessive-compulsive disorder and
      attention deficit hyperactivity disorder. However, there are unequivocal
      differences between Sydenham's chorea and Tourette's syndrome. There is initial
      evidence suggesting the beneficial effect of immunosuppression in Sydenham's
      chorea. Other autoimmune causes of chorea include systemic lupus erythematosus as
      well as paraneoplastic syndromes. The growing list of drugs associated with
      chorea include lamotrigine, methadone and lithium. Among infectious agents, HIV
      is the leading reported cause of chorea. SUMMARY: Patients with sporadic chorea
      require a thorough work up because numerous causes can lead to this condition. It
      remains unconfirmed whether the pathogenic mechanisms of Sydenham's chorea are
      responsible for other conditions such as isolated obsessive-compulsive disorder
      or Tourette's syndrome. Drugs and infectious agents, especially HIV, are often
      implicated in the causes of chorea.

PMID- 15247539
TI  - Neurodegenerative disease and iron storage in the brain.
AB  - PURPOSE OF REVIEW: Iron is very important for normal regulation of various
      metabolic pathways. Neurons store iron in the form of ferrous ion or
      neuromelanin. In specific disorders the axonal transport of iron is impaired,
      leading to iron deposition which in the presence of reactive oxygen species
      results in neurodegeneration. RECENT FINDINGS: Recent developments in genetics,
      including the finding of mutations in the pantothenate kinase gene and ferritin
      light chain gene, have demonstrated a direct relationship between the presence of
      a mutation in the iron-regulatory pathways and iron deposition in the brain
      resulting in neurodegeneration. These two disorders now add to our understanding
      of the mechanism of disease due to dysfunction of iron-regulatory pathways. In
      addition to these disorders there may be several other mutations of iron
      regulatory genes or related genes that are yet to be found. The animal models of
      disease have also added value to this area. SUMMARY: In this review we provide a
      summary of recent developments in the field of movement disorders with
      abnormalities in iron transport, and the current evidence in neurodegenerative
      disorders such as Parkinson's disease.

PMID- 15247540
TI  - Phenotyping and genotyping: lessons to be learned from studying behaviour and its
      neurophysiological correlate.

PMID- 15247541
TI  - Update on stroke.
AB  - PURPOSE OF REVIEW: This review highlights some advances in the areas of
      epidemiology, therapy, and imaging of acute stroke. RECENT FINDINGS: Studies
      published in 2003 provided new insights into the epidemiology of stroke. The
      African American Antiplatelet Stroke Prevention Study found that traditional
      stroke risk factors are still undiagnosed and undertreated, particularly in
      minorities. Cohort studies have identified incident silent infarcts as risk
      factors for stroke and history of type I diabetes as a risk factor for death in
      patients with acute stroke. Cervical artery dissection, on the other hand, seems
      to have a benign course. Imaging has become an important tool for understanding
      the pathophysiology of stroke, as demonstrated in recent publications. New
      studies have shown the prognostic value of magnetic resonance imaging: it can
      predict the volume of ischemic tissue that will progress to infarction and
      detects cerebral microbleeds - a risk factor for intracranial hemorrhage.
      Computed tomographic scanning may have a role in selecting patients for
      thrombolysis, particularly when validated scales are used. Despite the barriers
      to the use of tissue plasminogen activator in the treatment of patients with
      stroke, data published this year show that it is a safe medication when used
      routinely in community and university hospitals. In addition to thrombolysis,
      other general medical measures, such as glucose control and adequate attention to
      nutritional status, can help improve the outcome of patients with stroke.
      SUMMARY: In acute stroke, recognition and modification of risk factors continue
      to be challenging tasks. Treatment of acute stroke should involve thrombolysis
      and attention to medical conditions that may influence outcome. New applications
      of magnetic resonance imaging and computed tomography may help guide stroke
      therapy.

PMID- 15247542
TI  - An update on neuroimaging of multiple sclerosis.
AB  - PURPOSE OF REVIEW: The advent of magnetic resonance imaging provided a powerful
      tool for monitoring the dynamics of pathological changes in multiple sclerosis,
      but conventional approaches offer only limited information that is directly
      relevant to clinical progression. Continued developments of imaging methods and
      their use for diagnosis, monitoring pathology and understanding disease
      progression are reviewed here. RECENT FINDINGS: Magnetic resonance imaging is now
      well established as a clinical test for multiple sclerosis, but the specific ways
      in which imaging information should best be incorporated into diagnostic criteria
      are still debated. New data defining the substantial pathology in grey matter,
      regional variation in the progression of pathology and the relationship between
      the spatial distribution of pathological changes and symptoms are providing an
      increasingly compelling description of changes relevant to disability. Molecular
      imaging approaches promise much more detailed descriptions. Functional magnetic
      resonance imaging, which suggests that adaptive functional changes could limit
      clinical expression of pathology, are providing further clues to the link between
      measures of pathology and disability. SUMMARY: New data further reinforce the
      view that pathology relevant to clinical progression of multiple sclerosis can be
      defined by imaging. A range of biologically more specific markers are becoming
      available using positron emission tomography, as well as magnetic resonance
      imaging.

PMID- 15247543
TI  - Neurodegenerative movement disorders: the contribution of functional imaging.
AB  - PURPOSE OF REVIEW: Functional imaging such as positron emission tomography and
      single-photon emission computed tomography provide sensitive tools to assess
      functional brain abnormalities associated with neurodegenerative disease. This
      review discusses recent findings in this field, with a focus on the detection and
      characterization of receptor binding and presynaptic dopamine changes in movement
      disorders. RECENT FINDINGS: The classical role of positron emission tomography
      and radioligands such as F-dopa and C-raclopride for investigating abnormalities
      of the presynaptic and postsynaptic dopaminergic system underlying Parkinson's
      disease, Parkinsonism and Huntington's disease has recently been made more
      powerful by the application of statistical mapping to localize changes in
      dopamine storage capacity and receptor binding across the whole brain at a voxel
      level. C-raclopride positron emission tomography provides an indirect marker of
      changes in levels of dopamine in the synaptic cleft. The application of this
      model in assessing dopamine changes in response to pharmacological, behavioural,
      motor task and magnetic stimulation in normal individuals and Parkinson's disease
      patients is reviewed. Recent studies using positron emission tomography and
      single-photon emission computed tomography to discriminate Parkinson's disease
      from essential tremor and Parkinsonism, the involvement of non-dopaminergic
      systems in Parkinson's disease and the role of cell transplantation in
      Parkinson's disease and Huntington's disease are also discussed. SUMMARY:
      Functional imaging techniques provide insight into the pathophysiology of
      Parkinson's disease, Parkinsonism, and Huntington's disease and the mechanisms of
      the progression of these diseases. They also play a role in assessing the
      efficacy of putative neuroprotective and restorative therapy, such as striatal
      infusions of neurotrophic factors and implants of fetal cells.

PMID- 15247544
TI  - Epilepsy.
AB  - PURPOSE OF REVIEW: The purpose of this review is to consider the current and
      potential role of neuroimaging from an epilepsy perspective, and to illustrate
      that by combining appropriate imaging techniques, neuroimaging can contribute
      greatly to elucidating the basic mechanisms of the various forms of epileptic
      disorders. RECENT FINDINGS: New magnetic resonance imaging sequences
      (magnetization transfer imaging) and positron emission tomography ligands
      (serotonergic system) were biologically validated in large groups of patients
      with localization-related epilepsies. Investigations in genetically determined
      homogenous patient populations (PAX6, juvenile myoclonic epilepsy) have
      strengthened the link between genetic defects and neuropathological targets
      (anterior commissure, thalamus). Magnetic resonance spectroscopy and
      electroencephalogram-triggered functional magnetic resonance imaging provided
      converging evidence for a key role of the thalamus in the generation of
      generalized seizures. The role of functional magnetic resonance imaging in
      identifying eloquent areas of cortex and its relationship to structural lesions,
      in particular malformations of cortical development, has been further elucidated.
      Longitudinal magnetic resonance imaging studies reported progressive volume loss
      after febrile convulsions and in active epilepsy. SUMMARY: Neuroimaging is
      essential for improving the efficacy and safety of therapeutic, in particular,
      surgical procedures. Investigations of larger, more homogenous genetic disorders
      and longitudinal rather than cross-sectional neuroimaging studies have advanced
      our knowledge about the cause and effect of epileptic disorders, and will
      ultimately link defects in molecular genetics with specific neuropathological
      targets.

PMID- 15247545
TI  - Update on neuroimaging in infectious central nervous system disease.
AB  - PURPOSE OF REVIEW: Neuroimaging constitutes an important component in the
      diagnosis of the underlying infectious agents in central nervous system
      infection. This review summarizes progress in the neuroimaging of infectious
      central nervous system disease since January 2003. It focuses on imaging of viral
      encephalitis, including that caused by exotic and emerging viruses, and on
      imaging in immunodeficient patients. RECENT FINDINGS: Diffusion-weighted imaging
      has been shown to be superior to conventional magnetic resonance imaging for the
      detection of early signal abnormalities in herpes simplex virus encephalitis but
      also in enterovirus 71 encephalitis and in West Nile encephalitis. Several
      studies defined the pattern of magnetic resonance imaging signal changes in
      endemic diseases such as West Nile encephalitis, Murray Valley encephalitis,
      enterovirus 71 encephalitis and Japanese encephalitis, but also in encephalitides
      due to ubiquitous viruses such as measles virus and Lyssavirus (rabies). In
      patients with HIV infection, apparent diffusion coefficient ratios obtained by
      diffusion-weighted imaging were significantly greater in lesions due to
      Toxoplasma encephalitis than in primary central nervous system lymphomas.
      SUMMARY: The diagnosis of unclear infectious central nervous system diseases
      remains a challenge. More recent magnetic resonance imaging techniques, such as
      diffusion-weighted imaging and magnetic resonance spectroscopy, provide
      additional helpful information. However, the mainstay of diagnosis remains the
      detection of viral DNA or serological markers of specific infectious agents
      within the cerebrospinal fluid.

PMID- 15247546
TI  - Endovascular treatment of cerebrovascular disease.
AB  - PURPOSE OF REVIEW: This review summarizes recent advances in endovascular therapy
      for cerebrovascular disease. RECENT FINDINGS: For ruptured aneurysms, the only
      large, randomized, controlled trial comparing surgical and endovascular treatment
      (the International Subarachnoid Aneurysm Trial) resulted in a significant
      reduction in death or dependency at 1 year, compared with surgery, providing
      sound evidence that coiling should be the treatment of first choice. Data from
      the International Study of Unruptured Intracranial Aneurysms demonstrated that
      treatment of unruptured anterior circulation aneurysms of under 7 mm with no
      history of subarachnoid hemorrhage is not justified. Embolization of
      arteriovenous malformations, as sole therapy, is curative only in a small
      percentage of cases, but can be part of a multimodal approach for reducing
      arteriovenous malformation size prior to surgery or radiotherapy. Partial
      treatment of complex arteriovenous malformations may be more dangerous than no
      treatment. Protection devices can reduce complication rates in carotid artery
      stenting, but scientific evidence is still lacking. Until the results of
      comparative trials are available, carotid artery stenting is indicated only in
      selected patients. Angioplasty and stenting of intracranial arterosclerotic
      disease is feasible but remains a high-risk procedure, indicated only in highly
      selected patients. In acute stroke therapy, new thrombolytics and clot-retrieval
      devices may result in better recanalization rates. SUMMARY: Advances in
      endovascular therapy have occurred in all areas of cerebrovascular disease. To
      obtain maximal patient benefit, endovascular treatment should be performed as an
      interdisciplinary approach in high-volume centers. Importantly, long-term follow
      up review is necessary to clarify the overall role of endovascular treatment in
      the management of cerebrovascular disease.

PMID- 15247547
TI  - The autistic brain: birth through adulthood.
AB  - PURPOSE OF REVIEW: We discuss evidence of brain maldevelopment in the first years
      of life in autism and new neuroanatomical and functional evidence from later ages
      of development. RECENT FINDINGS: Head circumference, an accurate indicator of
      brain size in children, was reported to jump from normal or below normal size in
      the first postnatal months in autistic infants to the 84 th percentile by about 1
      year of age; this abnormally accelerated growth was concluded by 2 years of age.
      Infants with extreme head (and therefore brain) growth fell into the severe end
      of the clinical spectrum and had more extreme neuroanatomical abnormalities. In
      the frontal and temporal lobes in autism, there have been reports of abnormal
      increases in gray and white matter at 2 to 4 years; reduced metabolic measures;
      deviant diffusion tensor imaging results in white matter; underdeveloped cortical
      minicolumns; and reduced functional activation during socio-emotional, cognitive
      and attention tasks. Cerebellar abnormalities included abnormal volumes, reduced
      number and size of Purkinje neurons in the vermis and hemispheres, molecular
      defects, and reduced functional activation in posterior regions. SUMMARY: A new
      neurobiological phenomenon in autism has been described that precedes the onset
      of clinical behavioral symptoms, and is brief and age-delimited to the first two
      years of life. The neurobiological defects that precede, trigger, and underlie it
      may form part of the developmental precursors of some of the anatomical,
      functional, and behavioral manifestations of autism. Future studies of the first
      years of life may help elucidate the factors and processes that bring about the
      unfolding of autistic behavior.

PMID- 15247548
TI  - Intracranial neuronavigation with intraoperative magnetic resonance imaging.
AB  - PURPOSE OF REVIEW: This is an invited review regarding the use of intraoperative
      magnetic resonance imaging in the neurosurgical setting. The medical literature
      evaluating the intraoperative use of magnetic resonance imaging for neurosurgery
      has increased steadily since the implementation of this technique 10 years ago.
      The present review discusses recent findings and the current use of
      intraoperative magnetic resonance imaging in neurosurgery with special emphasis
      on the quality of available evidence. RECENT FINDINGS: Intraoperative use of
      magnetic resonance imaging is a safe technique that enables the neurosurgeon to
      update data sets for navigational systems, to evaluate the extent of tumor
      resection and modify surgery if necessary, to guide instruments to the site of
      the lesion, and to evaluate the presence of intraoperative complications at the
      end of surgery. Although recent findings support the safety and efficacy of
      intraoperative magnetic resonance imaging for the above-mentioned purposes, there
      is no convincing evidence regarding its prognostic significance in the
      neurosurgical setting. SUMMARY: Although the use of intraoperative magnetic
      resonance imaging in neurosurgery has increased significantly within the last 10
      years, currently there are less than two dozen dedicated intraoperative units in
      the United States. The popularization of this technique depends on both economic
      justification and high-quality scientific evidence supporting its prognostic
      importance regarding patient outcome.

PMID- 15247551
TI  - alpha-defensins released into stimulated CD8+ T-cell supernatants are likely
      derived from residual granulocytes within the irradiated allogeneic peripheral
      blood mononuclear cells used as feeders.
AB  - We recently demonstrated the ability of human beta-defensins to inhibit HIV-1
      replication in vitro and demonstrated that alpha-defensins account for the great
      majority of beta-chemokine independent antiretroviral activity in stimulated CD8+
      T-cell culture supernatants. In a follow-up study aimed at defining specific
      subpopulations of CD8+ T-cells that produce alpha-defensins, we have found that
      in the absence of irradiated allogeneic peripheral blood mononuclear cells
      (PBMC), stimulated CD8+ T-cell supernatants do not contain alpha-defensins. In
      our present work, we define residual granulocytes within PBMC fractions as the
      likely source. In addition, we describe in vitro conditions that promote the
      internalization of alpha-defensins by cells not natively producing these
      proteins, thus confounding our ability to define true alpha-defensin producer
      cells. In light of these findings, alpha-defensins released into stimulated CD8+
      T-cell supernatants are unlikely to be derived from the CD8+ T-cells themselves.
      Moreover, our data imply that under some experimental conditions, a soluble
      noncytolytic anti-HIV-1 factor other than beta-chemokines is either not produced
      by CD8+ T-cells or is present in too small quantity to be effective.

PMID- 15247552
TI  - An inexpensive, simple, and manual method of CD4 T-cell quantitation in HIV
      infected individuals for use in developing countries.
AB  - CD4+ T lymphocytes are currently the most common surrogate marker indicating
      immune status and disease progression with HIV infection. The cost of monitoring
      disease progression and response to therapy is still prohibitively expensive.
      Flow cytometry is the gold standard for the estimation of CD4+, but the high
      initial investment for this technology and expensive reagents makes it
      unaffordable for developing countries like India. We evaluated the Coulter
      cytosphere assay for quantifying CD4+ T lymphocytes in comparison with the
      standard method, flow cytometry, in 122 HIV-infected individuals. The correlation
      coefficient of the cytosphere assay compared with that of flow cytometry for CD4+
      T lymphocytes was 0.97 (P< 0.0001), with a confidence interval of 0.95 to 0.98.
      The sensitivity, specificity, positive predictive value, and negative predictive
      value of the cytosphere assay in enumerating absolute CD4+ T-lymphocyte counts of
      less than 200/microL were 94.9%, 96.4%, 92.5%, and 97.6%, respectively. This is a
      simple inexpensive method and has a strong correlation with flow cytometry.
      Hence, the cytosphere assay can be an alternate to flow cytometry for the
      estimation of CD4+ T-lymphocyte counts, especially in resource-poor settings of
      developing countries, for monitoring HIV progression and response to therapy.

PMID- 15247553
TI  - Comparison of once-daily atazanavir with efavirenz, each in combination with
      fixed-dose zidovudine and lamivudine, as initial therapy for patients infected
      with HIV.
AB  - BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has
      pharmacokinetics that allow once-daily dosing, and it is not associated with
      significant PI-associated dyslipidemia. METHODS: A randomized, double-blind,
      double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and
      safety of atazanavir 400 mg administered once daily with efavirenz 600 mg
      administered once daily in combination with open-label fixed-dose zidovudine plus
      lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV
      RNA level. The primary efficacy end point was the proportion of treated patients
      with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA
      levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of
      patients receiving efavirenz (intent-to-treat, difference; 95% confidence
      interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable
      magnitudes and rates in the 2 treatment arms (mean change at week 48: 176
      cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated
      patients relative to comparator-treated patients did not demonstrate significant
      increases in total cholesterol, fasting low-density lipoprotein cholesterol, or
      fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin
      elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir
      treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For
      initial HIV treatment, a highly active antiretroviral therapy regimen of
      atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the
      combination of efavirenz/zidovudine/lamivudine.

PMID- 15247555
TI  - Absolute CD4 vs. CD4 percentage for predicting the risk of opportunistic illness
      in HIV infection.
AB  - Current guidelines recommend consideration of CD4 cell percentage as well as CD4
      cell count in therapeutic decisions. The relative value of CD4 cell count
      compared with CD4 cell percentage in predicting risk of AIDS-defining illnesses
      (ADIs) in the post-HAART (highly active antiretroviral therapy) era is unknown.
      Data from an observational clinical cohort of adult HIV-infected patients were
      used to assess the risk of developing an ADI associated with specific absolute
      CD4 counts (CD4) and CD4%'s (CD4%) using all CD4-CD4% pairs obtained after
      January 1996. The incidence of developing an ADI was assessed over a maximum of 6
      months after the CD4-CD4% pair was obtained. Using multivariable negative
      binomial regression, the incidence rate ratio (IRR) for developing an ADI by CD4
      and CD4% categories was computed. A total of 15,736 CD4-CD4% pairs from 2185
      patients who developed 608 ADIs was analyzed. The IRR for developing an ADI by
      absolute CD4 was 17.9 (95% CI: 13.2, 24.4) events/100 person-years for <50
      cells/mm, 6.2 (95% CI: 4.4, 7.9) for 50-100 cells/mm, and 2.7 (95% CI: 1.9, 4.0)
      for 100-200 cells/mm, compared with the referent stratum of 200-350 cells/mm.
      Without adjustment for absolute CD4, the IRR was 14.4 (95% CI: 9.3,22.6) for CD4%
      <7%, 3.7 (95% CI: 2.4,5.9) for 7-14%, 1.9 (95% CI: 1.1, 3.1) for 15-21%, compared
      with the referent stratum of >21%. However, in a multivariable analysis adjusting
      for absolute CD4, CD4%, and other clinical and demographic variables, the
      absolute CD4 but not the CD4% was associated strongly with developing an ADI. The
      results suggest that CD4% adds little further predictive information after
      accounting for the absolute CD4 count for the short-term risk of developing an
      ADI. The absolute CD4 count is the more important measure of immune status and is
      preferred over the CD4% for making treatment decisions in HIV-infected adults.

PMID- 15247554
TI  - T-cell lymphoma in HIV-infected patients.
AB  - Linkage of AIDS and cancer registries has indicated an increase in T-cell
      lymphomas among individuals infected with the HIV. The characteristics of T-cell
      versus B-cell lymphoma in HIV-infected patients are not well described.
      Retrospectively, 11 cases of T-cell lymphoma were identified from the AIDS
      Lymphoma Registry at the University of Southern California. These patients were
      compared with 418 consecutive HIV-seropositive patients with B-cell lymphoma
      diagnosed and treated within the same time period. T-cell lymphomas comprised 3%
      of all AIDS lymphomas. Pathologic types included peripheral T-cell lymphoma in 5;
      anaplastic large cell lymphoma in 3; and angioimmunoblastic, enteropathy type,
      and human T-cell lymphotropic virus-I-related adult T-cell lymphoma/leukemia in 1
      case each. No differences in demographic characteristics, history of prior
      opportunistic infection, or immunologic characteristics were observed between T
      cell and B-cell cases. Extranodal involvement of the skin (36% vs. 2%, P < 0.001)
      and bone marrow (45% vs. 15%, P = 0.019) was significantly more common in T-cell
      lymphomas. The median survival of patients with T-cell lymphomas was not
      significantly different from that of B-cell lymphoma patients (10.6 vs. 6.6
      months, P = 0.13). T-cell lymphomas in HIV-infected patients represent a spectrum
      of pathologic types. T-cell lymphomas differ from B-cell cases in terms of a
      higher propensity for skin and bone marrow involvement. The median survival of
      patients with T-cell lymphoma is comparable to that of patients with B-cell AIDS
      related lymphoma.

PMID- 15247556
TI  - Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug
      interaction through cytochrome P-450 induction.
AB  - Lopinavir/ritonavir (LPV/RTV) is a CYP3A4 inhibitor and substrate; it also may
      induce cytochrome P-450 (CYP) isozymes. Phenytoin (PHT) is a CYP3A4 inducer and
      CYP2C9/CYP2C19 substrate. This study quantified the pharmacokinetic (PK) drug
      interaction between LPV/RTV and PHT. Open-label, randomized, multiple-dose, PK
      study in healthy volunteers. Subjects in arm A (n = 12) received LPV/RTV 400/100
      mg twice daily (BID) (days 1-10), followed by LPV/RTV 400/100 mg BID + PHT 300 mg
      once daily (QD) (days 11-22). Arm B (n = 12) received PHT 300 mg QD (days 1-11),
      followed by PHT 300 mg QD + LPV/RTV 400/100 mg BID (days 12-23). Plasma samples
      were collected on day 11 and day 22; PK parameters were compared by geometric
      mean ratio (GMR, day 22:day 11). P values <0.05 were considered significant.
      Following PHT addition, LPV area under the concentration-time curve (AUC0-12h)
      decreased from 70.9 +/-37.0 to 49.6 +/- 25.1 microg.h/mL (GMR 0.67, P = 0.011)
      and C0h decreased from 6.0 +/- 3.2 to 3.6 +/- 2.3 microg/mL (GMR 0.54, P =
      0.001). Following LPV/RTV addition, PHT AUC0-24h decreased from 191.0+/-89.2 to
      147.8+/-104.5 microg.h/mL (GMR 0.69, P = 0.009) and C0h decreased from 7.0+/-4.0
      to 5.3+/-4.1 microg/mL (GMR 0.66, P = 0.033). Concomitant LPV/RTV and PHT use
      results in a 2-way drug interaction. Phenytoin appears to increase LPV clearance
      via CYP3A4 induction, which is not offset by the presence of low-dose RTV.
      LPV/RTV may increase PHT clearance via CYP2C9 induction. Management should be
      individualized to each patient; dosage or medication adjustments may be
      necessary.

PMID- 15247557
TI  - Plasma ascorbate deficiency is associated with impaired reduction of
      sulfamethoxazole-nitroso in HIV infection.
AB  - OBJECTIVE: The objective of these studies was to determine the role of ascorbate
      deficiency in HIV infection in the defective detoxification of sulfamethoxazole
      nitroso, the metabolite thought to mediate sulfonamide hypersensitivity
      reactions. METHODS: Fifty-one HIV-infected patients and 26 healthy volunteers
      were evaluated. Vitamin supplementation histories were obtained, and blood
      samples were collected for determination of plasma ascorbate, dehydroascorbate,
      and cysteine concentrations, erythrocyte glutathione concentrations, and plasma
      reduction of sulfamethoxazole-nitroso in vitro. RESULTS: Plasma ascorbate
      concentrations were significantly lower in HIV-positive patients not taking
      vitamin supplements (29.5 +/- 22.3 microM) than in healthy subjects (54.8 +/-
      22.3 microM; P = 0.0005) and patients taking 500-1000 mg of ascorbate daily (82.5
      +/- 26.3 microM; P < 0.0001). Plasma ascorbate deficiency was strongly correlated
      with impaired reduction of sulfamethoxazole-nitroso to its hydroxylamine (r =
      0.60, P < 0.0001), and during in vitro reduction, the loss of plasma ascorbate
      was strongly associated with the amount of nitroso reduced (r = 0.70, P <
      0.0001). Ascorbate added ex vivo normalized this reduction pathway. Erythrocyte
      glutathione concentrations were significantly lower in HIV-positive patients
      (0.98+/-0.32 mM) than in healthy subjects (1.45+/-0.49 mM; P = 0.001), but this
      finding was unrelated to ascorbate supplementation. There was trend toward lower
      plasma cysteine concentrations in patients (8.4+/-3.9 microM) than in controls
      (10.3+/-4.3 microM), but this trend was similarly unrelated to ascorbate
      supplementation. Dehydroascorbate concentrations were not significantly higher in
      HIV-positive patients (7.4+/-10.5%) than in healthy controls (4.0+/-6.2%), even
      in the subset of patients taking ascorbate (8.4+/-9.4%). CONCLUSIONS: Ascorbate
      deficiency is common in HIV-positive patients and is associated with impaired
      detoxification of sulfamethoxazole-nitroso, the suspected proximate toxin in
      sulfonamide hypersensitivity. Patients taking daily ascorbate supplements (500
      1000 mg) achieved high plasma ascorbate concentrations and did not show this
      detoxification defect. Ascorbate deficiency (or supplementation) was not
      associated with changes in glutathione or cysteine concentrations. These data
      suggest that ascorbate deficiency, independent of thiol status, may be an
      important determinant of impaired drug detoxification in HIV infection.

PMID- 15247558
TI  - Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role
      of mutagenically separated polymerase chain reaction as a tool for monitoring
      zidovudine-resistant HIV-1 in resource-limited settings.
AB  - As the number of HIV-1-infected individuals receiving antiretroviral drugs has
      been rapidly increasing in developing countries, there is an urgent need for drug
      resistance genotype information of non-B subtype HIV-1 and for the establishment
      of a practical system of monitoring drug-resistant viruses. This study first
      sequenced the reverse transcriptase region of HIV-1 in 112 infected individuals
      who had been treated with zidovudine (AZT)/didanosine or AZT/zalcitabine as dual
      therapy at a government hospital in northern Thailand and then compared the above
      sequence method with mutagenically separated polymerase chain reaction (MS-PCR)
      for detecting M41L and K70R mutations. Concordant rates of detecting M41L and
      K70R mutations by the 2 methods were 96.9% (93/96) and 92.7% (89/96),
      respectively. The M41L and K70R MS-PCR could detect 86.4% of AZT-resistant
      strains with any resistance mutation, which was determined by the sequencing
      method. Then 292 drug-naive individuals were screened for the presence of drug
      resistant HIV-1 by the MS-PCR assay and it was found that 2 individuals (0.7%)
      carried viruses with either the M41L or K70R mutation. It is feasible to test a
      large number of samples with MS-PCR, which is sensitive, cheap, and easy to
      perform and does not require sophisticated equipment. The M41L and K70R MS-PCR is
      potentially a useful tool to monitor the spread of AZT-resistant HIV-1 in
      resource-limited countries.

PMID- 15247560
TI  - HIV incidence among high-risk Puerto Rican drug users: a comparison of East
      Harlem, New York, and Bayamon, Puerto Rico.
AB  - Significant differences in HIV-related risk behaviors have been found between
      Puerto Rican drug users in New York City (NY) and Puerto Rico (PR). An
      examination of HIV incidence rates and characteristics of seroconverters in each
      location was undertaken. Baseline and follow-up interviewing and HIV testing were
      conducted in 1998 to 2002 with seronegative Puerto Rican injection drug users
      (IDUs) and crack smokers from East Harlem, NY (n = 455) and Bayamon, PR (n =
      268). There were a total of 32 seroconverters, 9 in NY and 23 in PR, for
      seroconversion rates of 0.88/100 person-years at risk (pyr; 95% CI, 0.31-1.45) in
      NY and 3.37/100 pyr (95% CI, 2.02-4.72) in PR (P < 0.001). In PR, variables
      significantly related to seroconversion were younger age and using shooting
      galleries. Being in methadone treatment was protective against seroconversion. In
      NY, crack use was significantly related to seroconversion. The higher
      seroconversion rate found in PR indicates a need to enhance HIV prevention
      efforts, including increasing methadone treatment and access to sterile syringes.
      The need to address sexual risk behaviors in both locations was also indicated.
      Resources focusing on reducing HIV transmission in the Caribbean should include
      efforts to target the drug use-HIV epidemic in PR.

PMID- 15247559
TI  - HIV transmission risk behavior among men and women living with HIV in 4 cities in
      the United States.
AB  - Determining rates of HIV transmission risk behavior among HIV-positive
      individuals is a public health priority, especially as infected persons live
      longer because of improved medical treatments. Few studies have assessed the
      potential for transmission to the partners of HIV-positive persons who engage in
      high-risk activities. A total of 3723 HIV-infected persons (1918 men who have sex
      with men [MSM], 978 women, and 827 heterosexual men) were interviewed in clinics
      and community-based agencies in Los Angeles, Milwaukee, New York City, and San
      Francisco from June 2000 to January 2002 regarding sexual and drug use behaviors
      that confer risk for transmitting HIV. Less than one quarter of women and
      heterosexual men had 2 or more sexual partners, whereas 59% of MSM reported
      having multiple partners. Most unprotected vaginal and anal sexual activity took
      place in the context of relationships with other HIV-positive individuals.
      Approximately 19% of women, 15.6% of MSM, and 13.1% of heterosexual men engaged
      in unprotected vaginal or anal intercourse with partners who were HIV-negative or
      whose serostatus was unknown. The majority of sexually active participants
      disclosed their serostatus to all partners with whom they engaged in unprotected
      intercourse. An estimated 30.4 new infections (79.7% as a result of sexual
      interactions with MSM) would be expected among the sex partners of study
      participants during the 3-month reporting period. Eighteen percent of 304
      participants who injected drugs in the past 3 months reported lending their used
      injection equipment to others. In addition to the more traditional approaches of
      HIV test counseling and of focusing on persons not infected, intensive prevention
      programs for persons with HIV infection are needed to stem the future spread of
      the virus.

PMID- 15247561
TI  - Decline in perinatal HIV transmission in New York State (1997-2000).
AB  - BACKGROUND: Perinatal HIV transmission has declined significantly in New York
      State (NYS) since implementation of a 3-part regimen of zidovudine prophylaxis in
      the antenatal, intrapartum, and newborn periods. This study describes the factors
      associated with perinatal transmission in NYS from 1997 to 2000, the first 4
      years of NYS's comprehensive program in which all HIV-exposed newborns were
      identified through universal HIV testing of newborns. METHODS: This population
      based observational study included all HIV-exposed newborns whose infection
      status was known and their mothers identified in NYS through the universal
      Newborn HIV Screening Program (NSP) from February 1997 to December 2000.
      Antepartum, intrapartum, newborn, and pediatric medical records of HIV-positive
      mothers/infants were reviewed for history of prenatal care, antiretroviral
      therapy (ART), and infant infection status. Risks associated with perinatal HIV
      transmission were examined. RESULTS: Perinatal HIV transmission declined
      significantly from 11.0% in 1997 to 3.7% in 2000 (P < 0.05). Prenatal ART was
      associated with a decline in perinatal HIV transmission both for monotherapy
      (5.8%, relative risk [RR] = 0.3, 95% confidence interval: 0.2%-0.5%) and
      combination therapy [2.4%, RR = 0.1, 95% confidence interval: 0.1%-0.2%) compared
      with no prenatal antiretroviral prophylaxis (P < 0.05). CONCLUSIONS: Public
      health policies to improve access to care for pregnant women and advances in
      clinical care, including receipt of appropriate preventive therapies, have
      contributed to declines in perinatal HIV transmission in NYS.

PMID- 15247562
TI  - Population-based surveillance of HIV-associated cancers: utility of cancer
      registry data.
AB  - Long-term cancer risks are uncertain in HIV-infected persons, particularly those
      using highly active antiretroviral therapy (HAART). Timely, population-based
      surveillance of HIV-associated malignancies in the United States has been
      challenging because of various data inadequacies. Cancer registries represent a
      resource for this surveillance, if uncertainties around accurate differentiation
      of HIV-associated and unassociated cancers can be resolved. To inform the utility
      of cancer registry data for classifying and monitoring HIV-associated cancers,
      the completeness and quality of cancer registry-available information about
      patient HIV status was assessed. For all 10,126 non-Hodgkin lymphomas (NHLs),
      1497 Hodgkin lymphomas (HLs), and 895 anal cancers reported to the Greater San
      Francisco Bay Area registry during 1990-1998, 6 indicators of patient HIV status
      were retrieved from 2 cancer registry-available sources (cancer registry records,
      death records) and from linkage with the California AIDS registry. Cross
      tabulations were used to examine the distributions of patients with evidence of
      positive HIV status by indicator and source. Together, 5 cancer registry
      available HIV indicators identified 25% more presumed HIV-positive NHL patients
      and nearly 50% more HL and anal cancer patients than were detected by AIDS
      registry linkage. Eighty-three percent of NHL patients and at least half of HL
      and anal cancer patients were identified by multiple sources of HIV indicators,
      and most individual indicators agreed acceptably with others. However, optimal
      strategies for classifying HIV-associated patients differed by cancer site. At
      least in this region, cancer registry data represent a useful resource for
      monitoring HIV-associated lymphomas and anal cancer and may offer benefits over
      linkage-based means in the age of HAART.

PMID- 15247563
TI  - Surveillance of HIV-1 subtypes among heterosexuals in England and Wales, 1997
      2000.
AB  - The molecular diversity and demographic characteristics among 976 anti-HIV-1
      positive heterosexuals attending 15 sexually transmitted infection (STI) clinics
      participating in an unlinked anonymous HIV prevalence serosurvey in England and
      Wales during 1997-2000 were investigated. Subtypes were assigned by heteroduplex
      mobility assay or sequencing of the p17/p24 region of gag and the V3/V4 region of
      env and by sequencing of the protease gene. Overall, there was no significant
      change in the subtype distribution, with subtype C accounting for the majority
      (32%) of subtyped infections. Subtypes B (29%), A (12%), circulating recombinant
      forms (CRFs, 9%), unique recombinant forms (URFs, 8%), and subtypes D-H (8%) were
      also detected. Thirty-nine percent of infections in men were with subtype B,
      whereas subtype C was most common (38%) in women. Logistic regression analyses
      showed the relative risk (RR) of infection with a non-B subtype, compared with
      subtype B, to be greater in African-born individuals (RR = 28.9, P < 0.01), among
      newly diagnosed infections (RR = 3.4, P < 0.01), and in women (RR = 2.4, P <
      0.01). These findings indicate a high level of genetic diversity among HIV
      infected heterosexual STI clinic attendees in England and Wales. Recently,
      subtype C has become most prevalent, particularly in younger age groups,
      suggesting recent acquisition of this viral strain. The high proportion of non-B,
      CRF, and URF infections among UK-born individuals is consistent with mixing
      between migrants and UK-born individuals in England and Wales. As migration
      patterns change, continued monitoring of HIV genetic diversity will aid
      understanding of transmission patterns.

PMID- 15247564
TI  - Multiple validated measures of adherence indicate high levels of adherence to
      generic HIV antiretroviral therapy in a resource-limited setting.
AB  - BACKGROUND: There are no validated measures of adherence to HIV antiretroviral
      therapy in resource-poor settings. Such measures are essential to understand the
      unique barriers to adherence as access to HIV antiretroviral therapy expands.
      METHODS: We assessed correspondence between multiple measures of adherence and
      viral load suppression in 34 patients purchasing generic Triomune antiretroviral
      therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai,
      India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day
      visual analog scale, electronic medication monitoring, and unannounced home pill
      count. HIV-1 load was determined at baseline and 12 weeks. RESULTS: Mean
      adherence was 91%-94% by all measures. Seventy-six percent of subjects had a
      viral load of <400 copies/mL at 12 weeks. All measures were closely correlated
      with each other (R = 0.77-0.89). Each measure was also significantly associated
      with 12-week HIV load. There was no significant difference between patient
      reported and objective measures of adherence. CONCLUSIONS: This sample of
      patients purchasing generic HIV antiretroviral therapy has among the highest
      measured adherence reported to date. Patient-reported measures were closely
      associated with objective measures. The relative ease of administration of the 30
      day visual analog scale suggests that this may be the preferred method to assess
      adherence in resource-poor settings.

PMID- 15247565
TI  - Interleukin-7 induces HIV type 1 outgrowth from peripheral resting CD4+ T cells.

PMID- 15247566
TI  - HIV-1 resistance to dideoxynucleoside reverse transcriptase inhibitors: genotypic
      phenotypic correlations.

PMID- 15247567
TI  - Lipid abnormalities in HIV-Infected patients and lopinavir plasma concentrations.

PMID- 15247568
TI  - Adherence to antiretroviral therapy in HIV patients with psychiatric comorbidity.

PMID- 15247569
TI  - Active warming during emergency transport relieves acute low back pain.
AB  - STUDY DESIGN: Prospective randomized blinded trial in a prehospital emergency
      system. OBJECTIVES: To evaluate the effects of external active warming on acute
      back pain during rescue transport to hospital. BACKGROUND DATA: Acute low back
      pain is one of the complaints that most often entails a visit to the physician or
      use of the emergency system. Superficial (e.g., hydrocolloid packs) and deep
      heating (e.g., ultrasound) can relieve acute low back pain in a clinical setting.
      Recent data showed significant benefit for patients in pain from minor trauma
      treated by active warming during emergency transport. Accordingly, we tested the
      hypothesis that active warming would reduce pain and anxiety in patients with
      acute low back pain being transported to a hospital. METHODS: A total of 100
      patients were included in our study. We selected only those suffering from acute
      pain > 60 mm on a visual analog scale in the lower back. Patients were randomly
      assigned to two groups: active warming with a carbon-fiber electric heating
      blanket (Group 1) versus passive warming with a woolen blanket (Group 2) during
      transfer to hospital. RESULTS.: Pain scores on arrival at the hospital differed
      significantly between Group 1 and Group 2 (P < 0.01). In Group 1, pain reduction
      from 74.2 +/- 8.5 mm VAS to 41.9 +/- 18.9 mm VAS (P < 0.01) was noted between
      departure from the emergency site and arrival at the hospital. Pain scores
      remained practically unchanged in Group 2 (73.3 +/- 11.9 mm VAS and 74.1 +/- 12.0
      mm VAS). CONCLUSIONS: Active warming reduces acute low back pain during rescue
      transport.

PMID- 15247570
TI  - A ligament in the lumbar foramina: inverted Y ligament: an anatomic report.
AB  - OBJECTIVES: The objective of this study was to investigate the ligaments in the
      exit zone of lumbar foramen and describe their anatomic relationships with
      adjacent structures. Few studies have been reported on the ligaments of foramen
      and the anatomic relationships on the lumbar level. The ligament described in
      this study is novel since it has not been reported previously. METHODS: Ten male
      and five female cadavers were used to investigate intraforaminal area and
      ligaments of the lumbar level. The cadavers were filled with colored latex, and
      the lumbar foramen were examined under operative microscope. RESULTS: A lumbar
      foramen branched off into two or three main passages, composed of inverted Y
      ligament form. The medial lower arm of Y ligament was attached to the upper and
      anterior surface of the superior articular process of the lower corpus vertebra.
      Its lateral lower arm was attached to the upper surface of the area where the
      lower corpus vertebra and its pedicle met, and the upper arm was attached to the
      lower surface of the pedicle of upper vertebra where it met with transverse
      process. The anatomic properties of vascular and nervous structures in foramen
      and the relations among them are described. CONCLUSION: The ligament detected in
      the study was different from the other reported descriptions of foraminal
      ligaments. It divided the lumbar foramen into three passages. Because of its
      relations with adjacent structures, such as nerves and vessels, the inverted Y
      ligament may be an important structure for lumbar foramen. Thus, it may be an
      important anatomic landmark.

PMID- 15247571
TI  - Upregulation of the viability of nucleus pulposus cells by bone marrow-derived
      stromal cells: significance of direct cell-to-cell contact in coculture system.
AB  - STUDY DESIGN: Upregulation of the viability of nucleus pulposus cells by
      coculture with bone marrow-derived stromal cells using a novel culture system.
      OBJECTIVES: The objective was to apply a novel coculture system having direct
      cell-to-cell contact between nucleus pulposus cells and bone marrow-derived
      stromal cells for stimulation of nucleus pulposus cells. SUMMARY OF BACKGROUND
      DATA: Reinsertion of nucleus pulposus cells was effective for treatment of
      intervertebral disc degeneration. However, obtaining highly viable nucleus
      pulposus cells was necessary to achieve successful results. Thus, an alternative
      method to upregulate the biologic and metabolic viabilities of nucleus pulposus
      cells was desired. METHODS: Nucleus pulposus cells and bone marrow-derived
      stromal cells were isolated from New Zealand white rabbits. A 6-well culture
      plate and insert with track-etched membrane having 0.4 microm pores at the bottom
      were used for coculture. Nucleus pulposus cells were monocultured, cocultured
      conventionally (having no direct cell-to-cell contact) with bone marrow-derived
      stromal cells, or cocultured having direct cell-to-cell contact with bone marrow
      derived stromal cells. On day 4 of coculture, nucleus pulposus cells were
      evaluated for proliferation using WST-8 assay, deoxyribonucleic acid synthesis by
      measuring [H]-thymidine uptake, and proteoglycan synthesis by measuring [S]
      sulfate uptake. We also quantified cytokines in supernatants from the culture
      system. RESULTS: Cell proliferation, deoxyribonucleic acid synthesis, and
      proteoglycan synthesis of nucleus pulposus cells were significantly upregulated
      in samples cocultured having direct cell-to-cell contact. Moreover, evaluations
      of supernatants revealed that growth factors associated with proliferation and
      cellular metabolism of nucleus pulposus cells were increased. CONCLUSIONS: Direct
      cell-to-cell contact in coculture system between nucleus pulposus cells and bone
      marrow-derived stromal cells accomplished significant upregulation in viability
      of nucleus pulposus cells.

PMID- 15247572
TI  - Immortalization of human nucleus pulposus cells by a recombinant SV40 adenovirus
      vector: establishment of a novel cell line for the study of human nucleus
      pulposus cells.
AB  - STUDY DESIGN: Establishment and characterization of a de novo cell line derived
      from human nucleus pulposus cells using a recombinant simian virus 40 (SV40)
      adenovirus vector. OBJECTIVES: To assess the feasibility of human nucleus
      pulposus cell line procurement and to evaluate the character of the resultant
      outcome to better understand the nature of human nucleus pulposus cells. SUMMARY
      OF BACKGROUND DATA: Despite recent advances in disc cell biologic research, the
      fundamental nature of nucleus pulposus cells, especially in the context of human
      cell lines, is still not well understood. Therefore, a broad-based analysis of
      these cells is of significant necessity. Because of the limited amount of
      existing human cells, establishment of an immortal cell line would greatly
      facilitate resource supply. METHODS: After release of informed consent, tissue
      samples of nucleus pulposus were obtained from the lumbar intervertebral disc of
      a 19-year-old man undergoing anterior fusion for burst fracture. Samples with no
      apparent damage were selected and digested enzymatically for primary culture and
      then were infected with recombinant SV40 adenovirus vector (Ad/SV40). The
      infected cells were maintained in culture for more than 40 population doublings,
      after which they were considered immortalized. Next, confirmation of expression
      of T antigen was performed and resultant immortalized cell lines were designated
      and classified as human nucleus pulposus cell line derived from Ad/SV40 infection
      1 (HNPSV-1). HNPSV-1 cells were characterized and compared with their mother
      cells under two designated culture conditions: monolayer and three-dimensional.
      Morphologic and immunocytochemical analyses were performed at various intervals.
      Cell proliferation, DNA synthesis, proteoglycan synthesis, gene expression
      profiling, and karyotypic analyses were also performed. Moreover, HNPSV-1 cells
      were injected into rabbit discs to assess the presence of tumorigenesis. RESULTS:
      Recombinant SV40 adenovirus vector infected nucleus pulposus cells with
      relatively high efficiency (90%> at multiplicity of infection 100). HNPSV-1
      demonstrated marked prolongation of cell life with continuous cell doublings for
      over 5 months (60-100 cell population doublings). Despite significant increase in
      cell proliferation and DNA synthesis when compared with its mother cells,
      resultant cell lines expressed strikingly similar cell morphology and functional
      characteristics. Atypical karyotypes were noted; however, no apparent
      tumorigenesis was seen in rabbit discs 24 weeks after injection of HNPSV-1.
      CONCLUSIONS: HNPSV-1 was successfully established using recombinant SV40
      adenovirus vector. Results showed that human nucleus pulposus cells are capable
      of immortalization with maintenance of original cell characteristics. It is
      anticipated that these cells will be useful for in vitro studies of the biologic
      nature of human nucleus pulposus cells.

PMID- 15247573
TI  - Cervical ventral epidural pressure response to graded spinal canal compromise and
      spinal motion.
AB  - STUDY DESIGN: A laboratory investigation using a feline model of graded ventral
      spinal canal compromise was performed. OBJECTIVE: To quantify the effects of
      graded ventral spinal canal compromise, both in the static condition and in
      combination with passive spinal motion, on cervical ventral epidural pressure
      (CVEP). The CVEP effects of laminectomy are also investigated. SUMMARY OF
      BACKGROUND DATA: Spinal canal compromise, both in the static condition and in
      combination with passive spinal motion, has been implicated as a cause of spinal
      cord dysfunction. METHODS: Seventeen cats underwent anterior corpectomy of C3 and
      placement of a flexible ventral graded compression device incorporating a
      pressure transducer. Ten animals also underwent laminectomy of C3. The implant
      was advanced stepwise into the spinal canal. CVEP was measured, at each degree of
      canal compromise, in the flexed, extended, and neutral positions, as well as
      during neck movement. RESULTS: CVEP rose as a function of spinal canal
      compromise. In animals without laminectomy, mean CVEP was higher in the extended
      position and lower in the flexed position than in the neutral position. Mean CVEP
      during continuous passive neck movement was found to be higher than mean CVEP in
      the neutral position. Laminectomy was found to lower CVEP during all conditions
      examined, although substantial rises in CVEP were still observed in the presence
      of a residual ventral mass. All reported differences were statistically
      significant (P < 0.05). CONCLUSIONS: CVEP is elevated by both spinal canal
      compromise and spinal motion.

PMID- 15247574
TI  - Interruption of the bilateral segmental arteries at several levels: influence on
      vertebral blood flow.
AB  - STUDY DESIGN: The effect of ligation of the bilateral segmental arteries at the
      levels of T11, T12, and T13 on blood flow of the T12 vertebra was studied in a
      dog model. OBJECTIVES: To determine the reduction of the vertebral blood flow
      resulting from interruption of bilateral segmental arteries at one to three
      vertebral levels. SUMMARY OF BACKGROUND DATA: Intraoperative hemorrhage can be
      sometimes massive in patients with hypervascular spinal tumors, especially in
      radical resection such as total en bloc spondylectomy. The recent development of
      new embolization techniques ensures more aggressive, more extensive, and safer
      preoperative embolization for spinal tumors. METHODS: The blood flow of the T12
      vertebra of 12 female dogs was measured after ligation of the bilateral segmental
      arteries at one to three levels, including the T12. Spinal cord evoked potentials
      were recorded in this procedure. Spinal angiography using a silicon compound was
      performed on another 10 dogs after clipping and section of the bilateral
      segmental arteries. RESULTS: The blood flow of the T12 vertebra decreased to
      70.13 +/- 6.37% of the control value after ligation of the bilateral segmental
      arteries of T12, to 46.48 +/- 8.97% after ligation of the bilateral segmental
      arteries of T12 and either T11 or T13, to 24.11 +/- 8.31% after ligation of T11,
      T12, and T13, respectively. The angiogram after ligation and section of T12 and
      the two levels including T12 showed thick and clear contrast medium in the cut
      distal ends of the T12 segmental arteries. After interruption at three levels
      (T11, T12, and T13), however, the cut distal ends of the T12 segmental arteries
      were seen thin and faint on the angiogram. No significant changes occurred in
      spinal cord evoked potentials after ligation of the segmental arteries at three
      levels in all six dogs. CONCLUSION: Interruption of the bilateral segmental
      arteries at three levels, one target vertebra and the two adjacent vertebrae,
      reduced the blood flow of the target vertebra to one fourth of the control value
      in the lower thoracic spine in dogs. This result suggests that preoperative
      embolization at three levels, the levels of the tumor vertebra and the adjacent
      vertebrae above and below it, may reduce intraoperative hemorrhage effectively
      during total en bloc spondylectomy for hypervascular spinal tumors.

PMID- 15247575
TI  - Risk factors for adjacent segment degeneration after PLIF.
AB  - STUDY DESIGN: A retrospective study of 87 patients who underwent posterior lumbar
      interbody fusion (PLIF) at L4-L5 for L4 degenerative spondylolisthesis.
      OBJECTIVE: To clarify: 1) the correlation between radiologic degeneration of
      cranial adjacent segment and clinical results, 2) risk factors for radiologic
      degeneration of cranial adjacent segment, and 3) preoperative radiologic features
      of patients who underwent additional surgery with cranial adjacent segment
      degeneration. SUMMARY OF BACKGROUND DATA: Whereas PLIF with pedicle screw
      fixation has shown satisfactory clinical results, a solid fusion has been
      reported to accelerate a degenerative change at unfused adjacent levels,
      especially in the cranial level. Although several authors have reported the
      adjacent segment degeneration after PLIF, there are no previous reports of risk
      factors for adjacent segment degeneration after PLIF. MATERIALS AND METHODS:
      Eighty-seven patients who underwent PLIF for L4 degenerative spondylolisthesis
      and could be followed for at least 2 years were included in this study. We
      measured lumbar lordosis, scoliosis, laminar inclination angle at L3, facet
      sagittalization at L3-L4, facet tropism at L3-L4, preexisting disc degeneration
      at L3-L4, and lordosis at the fused segment. Progression of L3-L4 segment
      degeneration was defined as a condition in which disc narrowing, posterior
      opening, and progress of slippage in comparison with preoperative dynamic lateral
      radiographs. Patients were divided into three groups according to postoperative
      progression of L3-L4 degeneration: Group 1 with neither progression of L3-L4
      degeneration nor neurologic deterioration, Group 2 with progression of L3-L4
      degeneration but no neurologic deterioration, and Group 3 with an additional
      surgery required for neurologic deterioration. Correlation between clinical
      results and radiologic progression of L3-L4 degeneration, and risk factors for
      progression of radiologic degeneration were investigated. Further, preoperative
      radiologic features of Group 3 were studied to detect risk factors for clinical
      deterioration. RESULTS: There were 58 (67%) patients classified into Group 1, 25
      (29%) patients into Group 2, and 4 (4%) patients into Group 3. There was no
      significant difference in average age in each group. No obvious difference was
      observed in recovery rate between Groups 1 and 2. Laminar inclination angle and
      facet tropism in Group 3 were more significant than those in Groups 1 and 2.
      Further, apparent lamina inclination and facet tropism coexisted in Group 3.
      There were no obvious differences in other factors between each group.
      CONCLUSION: 1) There was no correlation between radiologic degeneration of
      cranial adjacent segment and clinical results. 2) Risk factors for postoperative
      radiologic degeneration could not be detected in terms of each preoperative
      radiologic factor. 3) Coexistence of horizontalization of the lamina at L3 and
      facet tropism at L3-L4 may be one of the risk factors for neurologic
      deterioration resulting from accelerated L3-L4 degenerative change after L4-L5
      PLIF.

PMID- 15247576
TI  - A Cochrane review of manipulation and mobilization for mechanical neck disorders.
AB  - STUDY DESIGN AND OBJECTIVES: Our systematic review of randomized trials assessed
      whether manipulation and mobilization relieve pain or improve
      function/disability, patient satisfaction, and global perceived effect in adults
      with mechanical neck disorders. SUMMARY OF BACKGROUND DATA: Neck disorders are
      common, disabling, and costly. METHODS: Computerized bibliographic databases were
      searched up to March 2002. Two independent reviewers conducted study selection,
      data abstraction, and methodologic quality assessment. Relative risk and
      standardized mean differences were calculated. In the absence of heterogeneity,
      pooled effect measures were calculated using a random effects model. RESULTS: Of
      the 33 selected trials, 42% were high quality trials. Single or multiple (3-11)
      sessions of manipulation or mobilization showed no benefit in pain relief when
      assessed against placebo, control groups, or other treatments for
      acute/subacute/chronic mechanical neck disorders with or without headache. There
      was strong evidence of benefit favoring multimodal care (mobilization and/or
      manipulation plus exercise) over a waiting list control for pain reduction
      [pooled standardized mean differences -0.85 (95% CI: -1.20 to -0.50)],
      improvement in function [pooled SMD -0.57 (95% CI: -0.94 to -0.21)] and global
      perceived effect [standardized mean differences -2.73 (95% CI: -3.30 to -2.16)]
      for subacute/chronic mechanical neck disorders with or without headache.
      CONCLUSIONS: Mobilization and/or manipulation when used with exercise are
      beneficial for persistent mechanical neck disorders with or without headache.
      Done alone, manipulation and/or mobilization were not beneficial; when compared
      to one another, neither was superior. There was insufficient evidence available
      to draw conclusions for neck disorder with radicular findings. Factorial design
      would help determine the active agent(s) within a treatment mix.

PMID- 15247577
TI  - The effect of intraoperative traction during posterior spinal instrumentation and
      fusion for adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective study comparing patients having traction and a
      control group not having traction during posterior spinal instrumentation and
      fusion (PSIF) for adolescent idiopathic scoliosis (AIS). OBJECTIVE: To evaluate
      the effect of intraoperative traction on surgical correction of AIS. SUMMARY OF
      BACKGROUND DATA: When the Cotrel-Dubousset instrumentation system was introduced,
      the use of intraoperative traction was advocated. However, there is no specific
      report documenting the effect of intraoperative traction on the correction of
      AIS. METHODS: The medical and radiologic records of 140 AIS patients treated by
      PSIF were reviewed. Forty of these patients had intraoperative traction using a
      head halter associated with lower extremity skin traction. The radiologic outcome
      was compared between the two groups intraoperatively (before instrumentation with
      the first rod) and after surgery using Student t tests (level of significance =
      0.05). RESULTS: The intraoperative and postoperative corrections of the coronal
      primary Cobb angle were similar for both groups, although the patients in the
      traction group had smaller preoperative Cobb angles and more flexible curves and
      were instrumented with more screws. The postoperative thoracic kyphosis was
      significantly increased in both groups. The lumbar lordosis at the 1-year follow
      up was maintained in the control group, but it was significantly decreased in the
      traction group. CONCLUSION: The authors do not recommend the routine use of
      intraoperative traction using a head halter combined with skin traction for all
      AIS patients undergoing PSIF. However, it could be helpful in selected cases,
      such as in patients having pelvic obliquity and requiring instrumentation of the
      pelvis.

PMID- 15247578
TI  - Estimation of patient dose and associated radiogenic risks from fluoroscopically
      guided pedicle screw insertion.
AB  - STUDY DESIGN: An experimental model for the assessment of patient dose and
      associated radiogenic risks associated with pedicle screw internal fixation
      surgical procedures. OBJECTIVES: To provide data for the accurate determination
      of patient effective dose, gonadal dose, and entrance skin dose from
      fluoroscopically assisted pedicle screw insertion procedures and to investigate
      the potential of both stochastic and deterministic radiogenic effects to occur
      following such procedures. SUMMARY OF BACKGROUND DATA: There is increased concern
      on radiation exposure of patients undergoing fluoroscopically guided
      interventional procedures. METHODS: The cumulative screening time and dose area
      product, for each fluoroscopic projection used, were monitored in 20 patients
      undergoing pedicle screw internal fixation. The dose absorbed by each
      radiosensitive organ/tissue was determined from direct measurements obtained
      using an anthropomorphic phantom appropriately loaded with thermoluminescence
      dosimeters. RESULTS: An average pedicle screw insertion procedure requires 1.2
      minutes and 2.1 minutes of fluoroscopic exposure along anteroposterior and
      lateral projections, respectively, resulting in a dose area product of 232 cGy cm
      and 568 cGy cm, correspondingly. Gender-specific normalized data for the
      determination of effective, gonadal, and entrance skin dose to patients
      undergoing fluoroscopically guided pedicle screw internal fixation procedures
      were derived. The effective dose from an average procedure was 1.52 and 1.40 mSv
      and the gonadal dose 0.67 and 0.12 mGy for female and male patients,
      respectively. The average radiogenic risks for fatal cancer and genetic defects
      were 115 and 4 per million of patients treated, respectively. Induction of skin
      injuries might be induced when fluoroscopy along the lateral projection is highly
      extended and the source to skin distance is kept low. CONCLUSIONS: Patient dose
      and radiogenic risks associated with an average pedicle screw internal fixation
      procedure are tolerable. However, for young patients with complex spinal
      disorders requiring extended fluoroscopy, radiogenic risks may be considerable.
      Present data may beused for estimation of effective dose, gonadal dose, and
      entrance skin exposure and associated radiogenic risks to patients undergoing
      fluoroscopically guided pedicle screw insertion in any institution.

PMID- 15247579
TI  - Can health care utilization explain the association between socioeconomic status
      and back pain?
AB  - STUDY DESIGN: Cross-sectional population-based study. OBJECTIVES: To assess
      whether the association between socioeconomic status and severe back pain can be
      explained by the preceding health care utilization for back pain. SUMMARY OF
      BACKGROUND DATA: The ways in which socioeconomic status affects the occurrence of
      back pain are unclear. METHODS: Age- and gender-adjusted odds ratios with 95%
      confidence intervals for the association between indicators of socioeconomic
      status and severe current back pain (high intensity and/or high disability:
      no/yes) were investigated in an interview among 770 study participants out of
      1113 study participants with a recent history of back pain in a survey among 2731
      adults. RESULTS: The point prevalence of severe current back pain (39.8%) was
      related to educational level and health insurance status. Prior health care
      utilization for back pain was about 2-fold more prevalent in adults with severe
      current back pain. Members of private health insurance (odds ratio 0.60, 95%
      confidence interval 0.37-0.99) were less likely to report prior consultation of a
      general practitioner for back pain. Members of sick funds for white-collar
      workers (odds ratio 2.81, 95% confidence interval 1.43-5.51) and private
      insurance (odds ratio 2.81, 95% confidence interval 1.02-6.24) and individuals
      with intermediate educational level (odds ratio 1.76, 95% confidence interval
      1.05-2.95) utilized more physical therapy for the treatment of back pain. After
      additionally adjusting for health care utilization, the associations between
      educational level or health insurance status and severe current back pain
      remained unchanged. CONCLUSIONS: The data suggest that education, health
      insurance status, and health care utilization are independently associated with
      severe current back pain in a society with universal access to health care.

PMID- 15247580
TI  - The frequency and associated factors of low back pain among a younger population
      in Turkey.
AB  - STUDY DESIGN: Open design cross-sectional questionnaire. OBJECTIVES: The aims of
      this study are to determine the frequency of low back pains in the younger
      population and the factors that have an influence on this frequency. SUMMARY OF
      BACKGROUND DATA: Low back pain is one of the most important social problems that
      causes injuries in the younger population. Low back pain frequency is around 30%
      among adolescents, and 88% of those with low back pain experiences in adolescence
      have low back pain in later years. Therefore, identifying and, if possible,
      preventing the associated factors in adolescence and young adulthood is essential
      for the solution of this social problem. METHODS: A total of 1,552 students from
      a total of 8,000 who had come from all parts of Turkey for university
      registration accepted to participate in the study and were given a questionnaire
      about low back pain experiences, disability, and possible associated factors.
      RESULTS: Low back pain frequency was found to be 40.9%. This rate increases with
      age. Abandonment of moderate level physical activity and traumas such as slipping
      on ice and falling down the stairs were identified as associated factors.
      CONCLUSIONS: Regular physical activity and the prevention of falls might be ways
      for decreasing the frequency of low back pain experiences among the youth and
      significantly influencing the frequency of low back pain in adult population.

PMID- 15247581
TI  - The effectiveness of standard care, early intervention, and occupational
      management in Workers' Compensation claims: part 2.
AB  - STUDY DESIGN: A prospective cohort. OBJECTIVES: To compare the effectiveness of
      standard care, early intervention treatment, and occupational management in the
      management of Workers' Compensation injury claims. SUMMARY OF BACKGROUND DATA:
      The current management of occupational back pain and work-related upper extremity
      disorders with either standard care or early intervention treatment appears to be
      ineffective. METHODS: A prospective cohort looked at the effect of one company
      with access to standard care (primary care) changing to occupational management
      (worksite encouragement to resume activity and work as soon as safely possible)
      and then to early intervention treatment (offsite work hardening). This
      information was then compared with the control company with access to early
      intervention treatment, which later changed to a combined occupational
      management/early intervention treatment approach. Survival analysis was used to
      attempt to explain differences in time to injury claim closure. RESULTS:
      Occupational management resulted in lower injury claim incidence, duration, and
      costs than early intervention treatment. Only the covariate of enhanced physical
      therapist (work hardening) involvement (2001 hazard rate ratio 17.41, 95%
      confidence interval 3.72-41.51 and 2002 hazard rate ratio 6.22, 95% confidence
      interval 2.51-15.40) was associated with delayed time to injury claim closure
      when the company had access to early intervention treatment. Only the covariate
      of serious injury was associated with delayed time to injury claim closure in the
      company when it had access to occupational management (hazard rate ratio 1.67,
      95% confidence interval 1.05-27.20). CONCLUSIONS: It is recommended that an
      occupational management approach, in comparison to early intervention treatment
      and standard care, be considered for management of occupational injuries.

PMID- 15247582
TI  - The Cell Saver in adult lumbar fusion surgery: a cost-benefit outcomes study.
AB  - STUDY DESIGN: Review of efficacy of Cell Saver in a nonrandomized group of
      patients undergoing lumbar fusion. OBJECTIVES: Determine the necessity and cost
      effectiveness of the use of Cell Saver for adult lumbar spine fusions. SUMMARY OF
      BACKGROUND DATA: Specific indications for the use of Cell Saver in adult lumbar
      fusion surgery have not been clearly determined. In addition to effectiveness in
      blood replacement, the economic benefits of the Cell Saver have not been
      evaluated. METHODS: A total of 102 consecutive cases of posterolateral fusion
      with internal fixation were reviewed retrospectively. There were 56 patients in
      the Cell Saver group and 46 patients in the control group. Recorded hospital
      medical and financial data were analyzed for each patient. RESULTS: There was a
      38% recovery rate of blood using the Cell Saver. This resulted in a decreased
      need for postoperative transfusion in the study group (1 U to 36% of patients)
      relative to the control group (1 U to 50% of patients). Significant predictors
      for surgery time were the number of levels fused (P < 0.0001), patient's weight
      (P = 0.0030), and use of Cell Saver (P = 0.0472). Significant indicators of blood
      loss were the number of levels fused (P < 0.0001) and surgical time (P = 0.0304).
      The average cost for blood-related charges in the Cell Saver group was 512
      dollars versus 270 dollars per patient in the control group. CONCLUSIONS.: While
      the Cell Saver group did require fewer postoperative transfusions, the difference
      was not as much as expected. In elective fusions for degenerative conditions of
      the lumbar spine, blood requirements can usually be satisfied with predonation of
      autologous blood. With contemporary practices of predonation, the use of the Cell
      Saver appears to be neither necessary nor cost-effective during most elective
      lumbar fusions.

PMID- 15247584
TI  - Single versus separate registration for computer-assisted lumbar pedicle screw
      placement.
AB  - STUDY DESIGN: This is a retrospective study conducted to evaluate the efficacy of
      single versus separate registration in assessing the pedicle screw accuracy in
      the computer-assisted lumbar spinal instrumentation. OBJECTIVES: To see if
      separate registration reduced lumbar pedicle screw misplacement. SUMMARY OF
      BACKGROUND DATA: Computer-assisted spinal instrumentation has been shown to
      improve pedicle screw installation accuracy, but 2.7% to 8% of screws still
      perforate the pedicular cortex. Suspected causes include differences in lumbar
      lordosis between preoperative CT scans and surgery. METHODS: Postoperative
      radiographs and CT scans were used to assess the accuracy of pedicle screw
      placement in 47 adult patients following computer-assisted lumbar spinal
      instrumentation. Twenty-two patients underwent single registration at one level,
      while the other 25 underwent registration at each level. RESULTS: The time
      required for a registration procedure on one level was 6 to 8 minutes, while the
      time required for application of a pedicle screw using computer-assisted
      techniques was an additional 6 to 10 minutes. The total number of screw
      placements was 118 in the single registration group and 130 in the separate
      registration group. In the former group, 85 (72%) pedicle screw placements were
      categorized as good, 28 (24%) were fair, and 5 (4%) were poor. All five poorly
      placed screws were placed in the lower lumbar or upper sacral spine with high
      mobility, and at levels without registration, with one causing root injury. In
      the latter group, 117 (90%) pedicle screw placements were good and 13 (10%) were
      fair. The difference in placement was found to be statistically significant
      (chi2, P = 0.0003). CONCLUSION.: Before the intraoperative real-time CT imaging
      is widely used, separate registration at each instrumented level during
      traditional computer-assisted lumbar spinal instrumentation is necessary to
      enhance the accuracy of screw placement.

PMID- 15247585
TI  - Sedation with ketamine during intradiscal electrothermal therapy.
AB  - STUDY DESIGN: A technical report. OBJECTIVES: To present a new and improved
      method to sedate patients during intradiscal electrothermal therapy (IDET).
      SUMMARY OF BACKGROUND DATA: The current standard of practice is to sedate
      patients with short-acting benzodiazepines and opioids during the coagulation
      phase of intradiscal electrothermal therapy. There are few data on the subject,
      but it is estimated that between 5% and 20% of IDET procedures are either aborted
      early or switched to a lower heating temperature because patients cannot tolerate
      the optimal, recommended heating protocol. A priori, one must assume these
      patients are more likely to fail their treatment than those who are able to
      tolerate complete heating. METHODS: The authors treated 9 patients receiving
      intradiscal electrothermal therapy who were unable to tolerate the latter portion
      of their heating protocol secondary to axial low back pain despite high doses of
      opioids, with low dose ketamine. This paper outlines our experience with "rescue"
      doses of ketamine, along with the rationale and guidelines for its use. RESULTS:
      After receiving ketamine, all patients were able to complete the full intradiscal
      electrothermal therapy heating protocol. The rescue dosages of ketamine ranged
      from 15 to 55 mg. The dosages of midazolam used to prevent the psychomimetic
      effects of ketamine ranged from 3 to 7 mg. Oxygen saturation and hemodynamic
      parameters did not change significantly after ketamine was administered, and all
      patients remained responsive throughout the procedure. There were no adverse
      effects or complications reported. CONCLUSIONS: When used judiciously to treat
      axial back pain during intradiscal electrothermal therapy heating, ketamine is a
      safe and effective rescue medication.

PMID- 15247586
TI  - Re: Ruf M, Harms J. Posterior hemivertebra resection with transpedicular
      instrumentation: early correction in children aged 1 to 6 years. Spine.
      2003;28:2132-8.

PMID- 15247588
TI  - Spinal cord repair with acidic fibroblast growth factor as a treatment for a
      patient with chronic paraplegia.
AB  - STUDY DESIGN: We present a case of a patient with chronic paraplegia with a
      complete spinal cord gap resulting from a stabbing injury 4 years ago recovering
      after an innovative surgical strategy. OBJECTIVES: To demonstrate the clinical
      outcome of surgical repair with sural nerve graft with fibrin glue containing
      acidic fibroblast growth factor in a patient with chronic spinal cord injury.
      SUMMARY OF BACKGROUND DATA: Spinal cord injury usually causes permanent
      disability, and there had been not effective surgical technique to obtain
      satisfactory functional motor recovery, particularly in chronic patients.
      Previous studies have revealed that acidic fibroblast growth factor could promote
      axonal regeneration and reduce neuronal death in adult rats with spinal cord
      injury. METHODS: The spinal cord gap at T11 level was bridged with 4 sural nerve
      grafts that redirected specific pathways from white to gray matter. The grafted
      area was stabilized with fibrin glue containing acidic fibroblast growth factor.
      RESULTS: Before the operation, the paraplegia was identified as ASIA-C, with a
      motor score for the right and left legs of 12 and 0, respectively, a pinprick
      score of 77, and 77 on a light touch of left side limbs. His functional status
      improved from being wheelchair-bound to being able to ambulate independently with
      a walker 2-and-a-half years after surgery. At this stage, paraplegia was ASIA-D,
      with motor scores for the right and left legs of 15 and 12, respectively, 86 for
      a pinprick, and 86 for a light touch of left side limbs. CONCLUSIONS: This case
      demonstrated significant motor recovery attained in a patient with chronic
      paraplegia following a repair surgery with nerve graft and growth factor.

PMID- 15247589
TI  - Antifungal penetration into normal rabbit nucleus pulposus.
AB  - STUDY DESIGN: A rabbit model was used to assess the penetration into the nucleus
      pulposus of 3 commonly used antifungal medications: amphotericin B, amphotericin
      B lipid complex, and fluconazole. OBJECTIVES: The purpose of this study was to
      quantitate the penetration of antifungal medications into the normal rabbit
      nucleus pulposus. SUMMARY OF BACKGROUND DATA: Fungal infections of the spine are
      rarely, if ever, treated with medical management alone. Although antibiotic
      penetration into the nucleus pulposus has been studied extensively, no previous
      studies have attempted to quantitate the penetration of antifungals into the
      nucleus pulposus. METHODS: Twenty-four rabbits were given 2 doses of 1 of the
      antifungal medications studied. One hour after completion of the second dose, the
      animal was killed and the thoracolumbar spine was excised en bloc. Specimens of
      nucleus pulposus and serum were obtained and sent to an outside laboratory for
      analysis. Gas chromatography was used to determine the fluconazole tissue levels,
      and a bioassay was used to measure amphotericin B tissue levels. RESULTS: Three
      animals in the amphotericin B group died either after the first or second dose of
      medication was administered. Although amphotericin B and amphotericin B lipid
      complex did not show adequate penetration into the nucleus pulposus in 12 out of
      12 animals, fluconazole reached therapeutic tissue levels in 5 out of 7 animals.
      CONCLUSIONS: Fluconazole showed superior penetration into the nucleus pulposus in
      an uninfected rabbit model when compared to amphotericin B and amphotericin B
      lipid complex. These findings were found to be statistically significant (P =
      0.021), and they suggest that fluconazole may be a better choice for empiric
      therapy of fungal spine infections while cultures and sensitivities are pending.

PMID- 15247590
TI  - Acute respiratory distress syndrome associated with pulmonary cement embolism
      following percutaneous vertebroplasty with polymethylmethacrylate.
AB  - STUDY DESIGN: A case of acute respiratory distress syndrome following
      percutaneous vertebroplasty is described. OBJECTIVE: To alert clinicians to the
      potential occurrence of acute respiratory distress syndrome following use of
      polymethylmethacrylate bone cement. SUMMARY OF BACKGROUND DATA: Noncardiogenic
      pulmonary edema has not been reported following intravertebral injection of
      polymethylmethacrylate. METHODS: A 68-year-old woman underwent percutaneous
      vertebroplasty for a painful L5 compression fracture under local anesthesia. A
      contralateral transpedicular approach was made to inject polymethylmethacrylate.
      RESULTS: On the third postoperative day, she developed arthralgia, myalgia,
      fever, and frequent coughing. Chest radiography revealed bilateral, multifocal,
      patchy consolidations, suggestive of acute respiratory distress syndrome, and a 5
      cm-long tubular radiopacity in the right pulmonary artery. She died 20 days after
      the vertebroplasty. CONCLUSION: This case illustrates that clinicians must be
      aware of the potential occurrence of acute respiratory distress syndrome in
      patients who received percutaneous vertebroplasty.

PMID- 15247591
TI  - A case with cauda equina syndrome due to bacterial meningitis of anterior sacral
      meningocele.
AB  - STUDY DESIGN: A case of a patient with anterior sacral meningocele that was
      misdiagnosed as perianal abscess is presented. After the transrectal aspiration,
      the patient developed meningitis and cauda equina syndrome. OBJECTIVE: To report
      a rare case of anterior sacral meningocele in which primary presentation was
      mimicking perianal abscess. SUMMARY AND BACKGROUND DATA: Anterior sacral
      meningocele is a rare example of spinal dysraphism. It is created by a herniation
      of a dural sac through a defect in the sacral wall. It is usually asymptomatic
      until later decades. Most of the presenting symptoms are related to the pelvic
      organs. In the management of anterior sacral meningocele, surgical treatment is
      necessary. METHODS: The reported case is that of a 35-year-old female with cauda
      equina syndrome due to bacterial meningitis of the anterior sacral meningocele.
      At the beginning, she presented signs and symptoms resembling perianal abscess.
      She was misdiagnosed as anorectal abscess according to the computed tomography
      findings. The patient then underwent transrectal aspiration. Following the
      aspiration, meningitis and cauda equina syndrome were developed. Meningitis was
      treated with the appropriate antibiotics, and the patient underwent
      rehabilitation for paraplegia and bladder and bowel incontinence. RESULTS:
      Following the rehabilitation program, the patient has recovered completely within
      8 months. CONCLUSION: This case represents a rare example of anterior sacral
      meningocele in which the patient was misdiagnosed as perianal abscess. Meningitis
      either iatrogenic or spontaneous may occur during the course of anterior sacral
      meningocele. Once it has occurred, it may result in severe morbidity and
      mortality. However, our case had been treated effectively, and she had regained
      her health with rehabilitation program.

PMID- 15247592
TI  - Extended cervicolumbar spinal epidural abscess associated with paraparesis
      successfully decompressed using a minimally invasive technique.
AB  - STUDY DESIGN: A case of a multisegmental, cervicothoracolumbar epidural abscess,
      in an 80-year-old man, successfully decompressed by using a minimally invasive
      technique, is presented. OBJECTIVE: To review risk factors, diagnosis, treatment,
      decompression techniques, and morbidity and mortality regarding spinal epidural
      abscess. SUMMARY OF BACKGROUND DATA: Extended spinal epidural abscess is a rate
      entity. To our knowledge, this is the first report of a multilevel spinal
      epidural abscess, completely decompressed by limited laminectomies in combination
      with the use of a silicon catheter, epidurally. METHODS: The clinical and
      radiographic features associated with spinal epidural abscess, as well as
      decompression technique, are presented. The 80-year-old man, with a one week
      history of urinary tract infection, presented with fever and low back pain, mild
      weakness in his legs and jaundice. He underwent bilateral limited laminectomies
      at T2-T3 and a right hemilaminectomy at L1-L2 and the pus was drained, under mild
      continuous suction, using a 2.7 mm outer and 1.3 mm inner diameter silicon
      catheter, inserted caudally and cranially into the epidural space, at both the
      laminectomy sites. RESULTS: The patient experienced immediate relief of the low
      back pain, gradual fever subsidence and full neurological recovery during the
      next 3 weeks. CONCLUSION: In cases of suspected acute epidural abscess,
      especially in elderly debilitating patients: the whole spine should be scanned by
      MRI to exclude the possibility of multilevel involvement and adequate pus
      drainage, when indicated, could be performed with the above described minimally
      invasive technique.

PMID- 15247595
TI  - Trends in sepsis-related neonatal mortality in the United States, 1985-1998.
AB  - BACKGROUND: In the United States, bacterial sepsis affects up to 32,000 live
      births annually. In the 1990s, intrapartum antibiotic prophylaxis (IAP) was
      recommended to prevent maternal-infant transmission of group B Streptococcus
      (GBS), a leading cause of sepsis occurring in the first week of life (early onset
      sepsis). Since IAP has been used, early onset GBS disease declined 70%; however,
      increased antibiotic use associated with IAP might lead to more severe or
      antimicrobial resistant etiologies of sepsis. To understand the influence of IAP
      on neonatal sepsis, in general, we evaluated neonatal mortality from sepsis
      before and after IAP recommendations were issued. METHODS: Using the National
      Center for Health Statistics Linked Birth/Infant Death Datasets, we compared
      trends in sepsis-related early neonatal mortality (<7 days) and late neonatal
      mortality (7-27 days) among singleton United States births from 1985 through 1991
      to 1995 through 1998 [data beyond 1998 not included because of International
      Classification of Diseases (ICD)-10/ICD-9 coding differences]. We compared trends
      in mortality between the 2 time periods by estimating the average annual percent
      change in mortality using log linear regression and stratified by gestational
      age. RESULTS: Combined early and late neonatal mortality from sepsis averaged
      39.6/100,000 live births from 1985 through 1991 and 31.8/100,000 live births from
      1995 through 1998. Early neonatal mortality from sepsis averaged 24.9/100,000
      live births from 1985 through 1991 and 15.6 from 1995 through 1998; late neonatal
      mortality averaged 14.8/100,000 live births from 1985 through 1991 and 16.2 from
      1995 through 1998. Early neonatal mortality declined more steeply after IAP
      recommendations were issued, 5.0% annually from 1995 through 1998 versus 3.0%
      annually from 1985 through 1991. Late neonatal mortality increased more from 1995
      through 1998, 5.0% annually compared with 0.5% from 1985 through 1991.
      CONCLUSIONS: Lower mortality rates and greater declines in early neonatal
      mortality from sepsis during 1995-1998 indicate greater survival of infants
      beyond 7 days of life and suggest an association with GBS disease prevention
      efforts. Thus these findings provide some evidence for continuing IAP for GBS
      colonized women. Our findings of apparent increasing trends in late neonatal
      mortality from sepsis necessitate follow-up with clinical studies.

PMID- 15247596
TI  - Rubella immunization in human immunodeficiency virus type 1-infected children:
      cause for concern in vaccination strategies.
AB  - BACKGROUND: HIV infection can have important although sometimes unexpected
      consequences, such as contributing to enlargement of the pool of rubella
      susceptible children. METHODS: At the Federal University of Sao Paulo, Brazil, we
      assessed response to rubella immunization at 15 months of age in 15 human
      immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children
      (SR) and 18 healthy control children born to HIV-seronegative mothers (CON).
      Blood samples were collected before and 3 months after vaccination. All HIV
      infected children had started highly active antiretroviral therapy during their
      first 6 months of life. Serum samples were tested with a rubella IgG enzyme
      linked immunosorbent assay kit. RESULTS: HIV children in immunologic categories
      2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from
      CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after
      vaccination were positively associated with CD4 T cell numbers and negatively
      associated with HIV viral load assessed immediately before vaccination. The
      percentage of children with protective antibodies after vaccination (above 10.0
      IU/mL) was also significantly different among groups (Fisher's exact test, P =
      0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%.
      CONCLUSIONS: HIV-infected children with a preserved immune system at measles
      mumps-rubella immunization can have a good response to rubella vaccine. In
      contrast, those in more advanced categories for HIV infection respond poorly.

PMID- 15247597
TI  - Vascular endothelial growth factor and blood-brain barrier disruption in
      tuberculous meningitis.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is characterized by disruption of the
      blood-brain barrier (BBB), cerebral edema and increased intracranial pressure
      (ICP). Vascular endothelial growth factor (VEGF) is a potent vascular
      permeability factor and a mediator of brain edema. AIMS: To investigate whether
      in children with TBM disruption of the BBB relates to VEGF production and to
      assess the effect of corticosteroids on Mycobacterium tuberculosis-induced VEGF
      production by mononuclear leukocytes. METHODS: Blood and CSF samples were
      collected from 26 children with stage 2-3 TBM and 20 controls. All patients
      received antituberculous and adjuvant corticosteroid therapy. Children were
      evaluated by ICP recording, computerized tomography scanning and outcome
      assessment at 6 months follow-up. BBB disruption was quantified by cerebrospinal
      fluid (CSF)-serum albumin ratios. VEGF concentrations were measured by enzyme
      linked immunosorbent assay. In vitro human monocytic THP-1 cells were stimulated
      with M. tuberculosis sonicate or culture supernatant, and VEGF production was
      measured in the presence or absence of corticosteroids. RESULTS: CSF VEGF
      concentrations were significantly higher in TBM patients than in the controls and
      correlated with mononuclear cell counts (r = 0.64; P = 0.001) and CSF-serum
      albumin ratio (r = 0.49; P = 0.015). CSF VEGF did not significantly correlate
      with elevated ICP. In vitro induction of VEGF production by M. tuberculosis
      sonicate or culture supernatant could be completely abrogated by corticosteroid
      treatment. CONCLUSIONS: Inflammatory cells secrete VEGF during TBM. CSF VEGF
      correlates with BBB disruption. Inhibition of VEGF may explain part of the
      clinical effect of adjuvant corticosteroid therapy in TBM.

PMID- 15247598
TI  - In situ diagnosis of central venous catheter-related bloodstream infection
      without peripheral blood culture.
AB  - BACKGROUND: Catheter-related bloodstream infections (CRBIs) are frequent
      complications of the use of long term central venous catheters (CVCs).
      Comparative quantitative culture of blood obtained via the CVC and a peripheral
      vein (PV) is a well-accepted method of diagnosing CRBI; however, an alternative
      definition for use when a PV culture is not available is desirable. METHODS: A
      computerized search of patient records identified all positive blood culture
      results from the St. Jude Children's Research Hospital Microbiology Laboratory
      between January 1996 and May 2001. Demographic data, catheter information and
      culture results were abstracted. Sensitivity, specificity, positive predictive
      value (PPV), and likelihood ratio were calculated for 2 alternative definitions
      of CRBI. RESULTS: Review of the medical records revealed 136 episodes of
      bacteremia that were evaluable for alternative definition 1 and 241 episodes that
      were evaluable for alternative definition 2. In patients with a double lumen CVC,
      CRBI can be diagnosed by a > or = 5-fold difference in colony-forming units/mL
      between the 2 lumens (alternative definition 1) with sensitivity, specificity,
      PPV and likelihood ratio of 61.8, 93.3, 92.2 and 9.22, respectively. In patients
      with a single or double lumen CVC, CRBI can be diagnosed when the CVC culture
      yields > or = 100 colony-forming units/mL (alternative definition 2) with
      sensitivity, specificity, PPV and likelihood ratio of 75.5, 69.1, 79.3, and 2.44,
      respectively. CONCLUSIONS: Our study suggests that comparison of colony counts
      from 2 lumens of a double lumen catheter is acceptable for diagnosis of CRBI when
      a PV culture is not available. Further validation is needed before discontinuing
      the recommendation to obtain a PV culture.

PMID- 15247599
TI  - Emergence of community-associated methicillin-resistant Staphylococcus aureus at
      a Memphis, Tennessee Children's Hospital.
AB  - BACKGROUND: An epidemiologic investigation was performed because of a perceived
      increase in infections caused by community-associated methicillin-resistant
      Staphylococcus aureus (MRSA) among children in the greater Memphis area. METHODS:
      We reviewed medical records of 289 children evaluated from January 2000 to June
      2002 at a children's hospital. Clinical criteria were applied to classify MRSA
      isolates as community-associated (n=51) or health care-associated (n=138). The
      relatedness of 33 archived S. aureus isolates was evaluated using pulsed field
      gel electrophoresis (PFGE) of Sma I-digested genomic DNA; a common pulsed field
      type was defined as > or = 80 % similarity based on Dice coefficients. PFGE
      profiles were compared with those in a national database of MRSA isolates.
      RESULTS: During the first 18 study months, 46 of 122 MRSA isolates (38%) were
      community-associated; this proportion increased to 106 of 167 isolates (63%)
      during the last 12 study months (P <.0001). Community-associated isolates were
      recovered from normally sterile sites as frequently as were health care
      associated isolates (16% versus 13%). PFGE revealed that 15 of 16 community
      associated isolates shared a common pulsed field type (USA300) observed in
      community-associated MRSA infections elsewhere in the United States and
      characterized by staphylococcal cassette chromosome mec type IV, clindamycin
      susceptibility and erythromycin resistance mediated by an msr A-encoded macrolide
      efflux pump. CONCLUSIONS: Community-associated MRSA has emerged as a potentially
      invasive pathogen among children in the greater Memphis area, and this phenomenon
      is not explained by spread of nosocomial strains into the community.

PMID- 15247601
TI  - Ten-year study on the effect of intrapartum antibiotic prophylaxis on early onset
      group B streptococcal and Escherichia coli neonatal sepsis in Australasia.
AB  - BACKGROUND: Intrapartum antibiotics have reduced the incidence of neonatal early
      onset (EO) group B streptococcal (GBS) disease. Some surveillance data suggest
      that this success may be at the cost of increasing rates of non-GBS infection,
      especially in premature neonates. OBJECTIVE: To examine rates of EOGBS infection
      and EO Escherichia coli neonatal sepsis in Australasia. METHODOLOGY: Analysis of
      trends in EO (<48 h age) GBS and E. coli sepsis from longitudinal prospective
      surveillance data collected from representative tertiary obstetric hospitals in
      each state of Australia and selected centers in New Zealand during a 10-year
      period from 1992 through 2001. Statistical analysis used Poisson regression.
      RESULTS: 206 GBS and 96 E. coli cases occurred in 298,319 live births during the
      study period. The EOGBS sepsis rate fell from a peak of 1.43/1000 live births in
      1993 to 0.25/1000 in 2001 (P < 0.001). The overall EO E. coli sepsis rate was
      0.32/1000. In babies with birth weight <1500 g, it was 6.20/1000. There was an
      overall trend to decreasing EO E. coli sepsis (P = 0.07), and there was no
      significant change in E. coli sepsis in babies <1500 g (P = 0.60). Sixty-nine
      percent of E. coli cases occurred in the <1500 g cohort; the case fatality rate
      in this group was 50%. The overall case fatality rate from E. coli sepsis was
      36%, and this rate remained stable during the study period (P = 0.47).
      CONCLUSIONS: The increasing use of intrapartum antibiotics produced a steady
      decline in EOGBS disease in Australasia. There was also a trend to decreasing EO
      E. coli sepsis in all babies, and the rate in very low birth weight infants
      remained stable.

PMID- 15247600
TI  - Ampicillin and penicillin concentration in serum and pleural fluid of
      hospitalized children with community-acquired pneumonia.
AB  - BACKGROUND: Optimal therapeutic efficacy of beta-lactam antibiotics for treatment
      of pneumococcal pneumonia is thought to be associated with the serum
      concentration greater than the minimum inhibitory concentration for 40-50% of the
      interdose interval at site of infection. OBJECTIVE: Establish whether intravenous
      administration of ampicillin 400 mg/kg/day or penicillin 200,000 IU/kg/day in 6
      divided doses reaches serum and or pleural concentrations above 4 microg/ml for
      at least 40% of the interdose interval. MATERIALS AND METHODS: Hospitalized
      healthy children 1 month-14 years old with community-acquired bacterial pneumonia
      and empyema were eligible. Blood samples were obtained 30 min (C1) and 3 h (C2)
      after an antibiotic dose. Pleural fluid samples were obtained 1 and 4 h after the
      same dose in which blood samples were obtained. The concentrations were measured
      by high performance liquid chromatography. RESULTS: The study included 17
      patients treated with ampicillin and 13 treated with penicillin. For ampicillin,
      mean serum concentrations were C1 37.3 +/- 19 microg/ml and C2 11 +/- 10.2
      microg/ml and mean pleural fluid concentrations were C1 25.8 +/- 9.9 microg/ml
      and C2 16.2 +/- 7.9 microg/ml. For penicillin, mean serum concentrations were C1
      21.8 +/- 16.4 microg/ml and C2 23.9 +/- 3.4 microg/ml. Mean pleural fluid
      concentrations were C1 10.9 +/- 2.2 microg/ml and C2 7.7 +/- 3.4 microg/ml. In 8
      of 30 patients, serum C2 was <4 microg/ml; in all of them serum concentrations
      were >4 microg/ml for >40% of the interdose interval. CONCLUSIONS: This study of
      the pharmacokinetics of beta-lactam antibiotics in children with bacterial
      pneumonia may help in the development of therapeutic guidelines for the treatment
      of pneumococcal pneumonia.

PMID- 15247602
TI  - Risk factors for disseminated candidiasis in children with candidemia.
AB  - OBJECTIVE: To determine the risk factors for disseminated infection in
      hospitalized children with candidemia. METHODS: We performed a nested case
      control study within a cohort of hospitalized children with candidemia. The
      cohort was defined by all patients with positive blood cultures for Candida
      species in a large, urban, academic, tertiary care children's hospital from 1998
      to 2001. Cases were patients with clinical, microbiologic or radiographic
      evidence of disseminated candidiasis. Controls were patients with no evidence of
      disseminated candidiasis. RESULTS: Among 168 total children with candidemia, the
      median age was 3.5 years (interquartile range, 0.6-14.3). There were 189 episodes
      of candidemia. Candida species included:Candida albicans (41%), Candida
      parapsilosis (24%), Candida glabrata (13%) and Candida tropicalis (9%). The most
      common underlying diagnoses were oncologic (24%), gastrointestinal (15%) and
      cardiac (10%) diseases. Eighty-nine patients (53%) were admitted to an intensive
      care unit, 46 (27%) to a general pediatric or surgical ward and 33 (20%) to the
      oncology ward. Of the 168 patients with candidemia, 153 were included in the
      analysis of risk factors for disseminated candidiasis. Of 153 (17%) patients, 26
      had evidence of organ dissemination. Organ involvement was most commonly
      identified in the lung (58%), followed by the liver (23%), kidney (16%), brain
      (12%), spleen (8%), eye (8%) and heart (8%). Eight of the 26 patients had
      evidence of dissemination to more than 1 organ. Independent risk factors for
      disseminated candidiasis were persistently positive blood cultures for Candida
      (>3 days) with a central venous catheter in place (odds ratio, 3.0; 95%
      confidence interval, 1.2, 7.8; P = 0.02) and immunosuppression (odds ratio, 2.9;
      95% confidence interval, 1.2, 7.0; P = 0.02). CONCLUSIONS: Prolonged duration of
      candidemia with a central venous catheter in place and immunosuppression were
      independent risk factors for disseminated candidiasis in children with
      candidemia. Furthermore review of the epidemiology of candidemia at our
      institution revealed a heterogeneous population of children at risk for
      candidemia and a predominance of non-albicans species as the cause of these
      infections. Future studies are needed to determine the extent of evaluation
      needed for detecting dissemination among children with candidemia and to explore
      interventions for its prevention.

PMID- 15247603
TI  - Invasive pneumococcal infections among hospitalized children in Bamako, Mali.
AB  - BACKGROUND: Prevention of invasive pneumococcal disease (IPD) in children is a
      global public health priority, and determination of the most common serotypes is
      crucial for vaccine development and implementation. METHODS: We performed
      prospective surveillance for IPD in hospitalized children in Bamako, Mali. All
      febrile children and others suspected to have invasive bacterial disease had an
      admission blood culture and cultures of additional anatomic sites when indicated.
      Standard microbiologic methods were used to identify, serotype and determine
      antibiograms for pneumococcal isolates. RESULTS: Of 2,049 children enrolled, 106
      (5%) had an IPD, including 47 cases of meningitis and 44 bacteremic pneumonias.
      The incidence was highest in infants (84/100,000/year). The overall IPD case
      fatality rate was 24%. Only 2 of 96 isolates were nonsusceptible to penicillin.
      The serotypes isolated were 5 (54%), 2 (14%), 7F (10%), 19F (8%), 6A/B (3%), 9V
      (3%), 1 (2%) and 14 (1%). CONCLUSIONS: IPD is common and frequently fatal among
      hospitalized children in Mali, but surprisingly little resistance has occurred.
      Notably, 91% of the serotypes causing IPD in Bamako children are found in the 11
      valent pneumococcal conjugate vaccine.

PMID- 15247604
TI  - Duration of hepatitis B immunity in low risk children receiving hepatitis B
      vaccinations from birth.
AB  - BACKGROUND: The duration of protection after hepatitis B vaccination of infants
      is unknown. METHODS: We determined antibody to hepatitis B surface antigen (anti
      HBs) at 4-13 years of age in 363 low risk children who had been vaccinated
      starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10
      mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B
      surface antigen (HBsAg)-positive mothers. RESULTS: Of low risk infants receiving
      a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was
      unknown and 24% (4 of 17) who had initially responded retained protective titers
      (> or = 10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did
      not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12),
      respectively, responded to a booster dose. In children of HBsAg-positive mothers,
      31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with
      nonprotective titers responded to a booster. In low risk children initially
      receiving a recombinant vaccine, 12.5% (26 of 208) and none (0 of 36) retained
      protective anti-HBs titers at 5 and 7 years of age, respectively. Of those who
      did not have protective titers, 90% (120 of 134) and 91% (32 of 35),
      respectively, responded to a booster. CONCLUSIONS: Anti-HBs disappeared by 5
      years of age in most children who were vaccinated with hepatitis B vaccine from
      birth. Although most children showed immunologic memory, one-third failed to
      demonstrate an anamnestic response to a booster dose. Additional long term
      studies of low risk infants are needed to determine duration of protection and
      the necessity for or timing of booster doses.

PMID- 15247605
TI  - Lack of association between hepatitis B birth immunization and neonatal death: a
      population-based study from the vaccine safety datalink project.
AB  - BACKGROUND: There have been no population-based studies of the potential
      association between neonatal death and newborn immunization with hepatitis B
      vaccine (HBV). METHODS: As part of the Vaccine Safety Datalink Project, we
      defined a birth cohort at Southern and Northern California Kaiser Permanente
      Health Plans of more than 350,000 live births from 1993 to 1998 and ascertained
      all deaths occurring under 29 days of age. We compared the proportions of deaths
      among birth HBV-vaccinated and unvaccinated newborns and reviewed the causes and
      circumstances of their deaths. We performed detailed clinical reviews of all HBV
      vaccinated neonates who died and a sample of unvaccinated neonates who died and
      who were matched to vaccinated deaths for days of life, sex, birth year and site
      of care. To avoid confounding, we categorized the causes of death as either
      "expected" or "unexpected" and performed a stratified analysis to compare
      mortality with immunization status. RESULTS: There were 1363 neonatal deaths
      during the study period. Whereas 67% of the entire birth cohort received HBV at
      birth, only 72 (5%) of the neonates who died were HBV-vaccinated at birth (P <
      0.01). We found no significant difference in the proportion of HBV-vaccinated
      (31%) and unvaccinated (35%) neonates dying of unexpected causes (P = 0.6).
      Further we could not identify a plausible causal or temporal relationship between
      HBV administration and death for the 22 vaccinated neonates who died
      unexpectedly. CONCLUSIONS: A relationship between HBV and neonatal death was not
      identified.

PMID- 15247606
TI  - Global health impact of soil-transmitted nematodes.

PMID- 15247607
TI  - Viral myocarditis.

PMID- 15247608
TI  - Cavitating tuberculosis in an infant: case report and literature review.
AB  - Primary cavitating tuberculosis is a rare complication of primary tuberculosis in
      young children. In the absence of a known adult source case, the diagnosis of
      tuberculosis in children can be difficult. We describe an 8-month-old baby with
      primary cavitating tuberculosis, in whom there was considerable delay in
      diagnosis, and review the literature.

PMID- 15247609
TI  - Human herpesvirus 8-related childhood mononucleosis: a series of three cases.
AB  - Human herpesvirus 8 has been implicated in the pathogenesis of a limited subset
      of lymphoproliferative disorders in adults, but its role in children is unclear.
      A prospective evaluation of children with atypical lymphocytosis residing in the
      Hualien area, where the incidence of adult Kaposi sarcoma is high, revealed 3
      cases caused by human herpesvirus 8.

PMID- 15247610
TI  - Influence of school closure on the incidence of viral respiratory diseases among
      children and on health care utilization.
AB  - We evaluated the effect of school closure on the occurrence of respiratory
      infection among children ages 6-12 years and its impact on health care services.
      During this period, there were significant decreases in the diagnoses of
      respiratory infections (42%), visits to physician (28%) and emergency departments
      (28%) and medication purchases (35%). The present study provides quantitative
      data to support school closure during an influenza pandemic.

PMID- 15247611
TI  - Characterization of a community cluster of group a streptococcal invasive disease
      in Maui, Hawaii.
AB  - A community cluster of severe group A streptococcal skin infections occurred in
      Maui, Hawaii with 3 fatal cases of necrotizing fasciitis in 2002. emm types 1,
      12, 58, 74, 85 and 109 were identified from 8 patients. emm types 74 and 109 have
      not been previously described in the United States according to the Centers for
      Disease Control and Prevention database. The identification of uncommon emm types
      suggested that group A streptococcal sero-types in Hawaii are different from
      those in the continental United States and can result in serious disease.

PMID- 15247612
TI  - Safety of mefloquine in infants with acute falciparum malaria.
AB  - We evaluated retrospectively the safety of mefloquine (25 mg/kg) for the curative
      treatment of uncomplicated Plasmodium falciparum malaria in 26 infants weighing
      <15 kg and managed during a 5-year period. Side effects were recorded in 30.8% of
      patients and consisted chiefly of mild and transient gastrointestinal symptoms.
      Mefloquine was safe in infants weighing <15 kg in our experience.

PMID- 15247613
TI  - Vagal nerve stimulator pocket infections.
AB  - Vagal nerve stimulator pocket infections are uncommon but can cause considerable
      morbidity. We describe 3 children from our institution and 8 others previously
      reported with infection after vagal nerve stimulator implantation for seizure
      control. Infection was suppressed but recurred despite appropriate antimicrobial
      therapy when the device remained in situ. Device removal was required in all
      patients to achieve cure.

PMID- 15247614
TI  - Progressive multifocal leukoencephalopathy after initiation of highly active
      antiretroviral therapy in a child with advanced human immunodeficiency virus
      infection: a case of immune reconstitution inflammatory syndrome.
AB  - Five weeks after commencing highly active antiretroviral therapy, a 12-year-old
      boy with advanced human immunodeficiency virus infection presented with acute
      cerebellar dysfunction and hemiparesis. Progressive multifocal
      leukoencephalopathy was diagnosed by cerebrospinal fluid polymerase chain
      reaction for JC virus and magnetic resonance imaging of the brain. Rapid and
      sustained improvement followed a prolonged course of glucocorticosteroid therapy
      while continuing antiretrovirals.

PMID- 15247615
TI  - Accidental drainage of a cerebral hydatid cyst into the peritoneal cavity.
AB  - Intracranial hydatidosis is more common in children than in adults. The most
      severe complication is anaphylactic response after direct rupture into the
      subarachnoid spaces. We report a case of brain hydatid cyst that was accidentally
      drained into the peritoneal cavity and was not complicated by an anaphylactic
      response or dissemination.

PMID- 15247616
TI  - Resistant Candida parapsilosis associated with long term fluconazole prophylaxis
      in an animal model.
AB  - We report an increased occurrence of fluconazole-resistant Candida parapsilosis
      after a 4-year period of antifungal prophylaxis in a premature animal neonatal
      intensive care unit. Although prevention of nosocomial fungal infections in
      premature infants is desirable, implementation of fluconazole prophylaxis should
      be undertaken with caution. Where such programs are in place, evaluation of
      fungal isolates for drug resistance should be considered.

PMID- 15247617
TI  - Facial nerve palsy after human herpesvirus 6 infection.
AB  - Facial nerve palsy has long been considered to have an infectious etiology,
      either viruses, mainly herpesviruses, or bacteria, such as Borrelia burgdorferi.
      We report for the first time the association of human herpesvirus 6 and facial
      palsy in a previously healthy 1-year 9-month-old boy who developed left facial
      nerve palsy 7 days after exanthema subitum caused by human herpesvirus 6.

PMID- 15247618
TI  - Pantoea agglomerans and thorn-associated suppurative arthritis.

PMID- 15247619
TI  - Staphylococcal skin infections.

PMID- 15247621
TI  - Prevention of group B streptococcal infection in a North-Italian area.

PMID- 15247622
TI  - Recurrent pericarditis after meningococcal infection.

PMID- 15247623
TI  - Profound lymphocytosis preceding chickenpox.

PMID- 15247624
TI  - Bringing genomics to the bedside: a cost-effective pharmacogenomic test?

PMID- 15247625
TI  - Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir
      hypersensitivity.
AB  - OBJECTIVE: Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue
      reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of
      patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity
      in Caucasians. Our aim was to confirm the presence of this genetic factor in our
      patients, and to determine whether genotyping for HLA B*5701 would be a cost
      effective use of healthcare resources. METHODS: Patients with and without
      abacavir hypersensitivity were identified from a UK HIV clinic. Patients were
      genotyped for HLA B*5701, and pooled data used for calculation of test
      characteristics. The cost-effectiveness analysis incorporated the cost of
      testing, cost of treating abacavir hypersensitivity, and the cost and selection
      of alternative antiretroviral regimens. A probabilistic decision analytic model
      (comparing testing versus no testing) was formulated and Monte Carlo simulations
      performed. RESULTS: Of the abacavir hypersensitive patients, six (46%) were HLA
      B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds
      ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on
      HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4
      132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on
      the choice of comparator, routine testing for HLA B*5701 ranged from being a
      dominant strategy (less expensive and more beneficial than not testing) to an
      incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per
      hypersensitivity reaction avoided. CONCLUSIONS: Abacavir hypersensitivity is
      associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this
      appears to be a cost-effective use of healthcare resources.

PMID- 15247626
TI  - Functional responses of human beta1 adrenoceptors with defined haplotypes for the
      common 389R>G and 49S>G polymorphisms.
AB  - OBJECTIVES: The human beta1-adrenoceptor (beta1-AR) is an important therapeutic
      target for cardiovascular diseases and has two common functional polymorphisms
      (49S>G and 389R>G). These polymorphisms have only been studied in isolation,
      however, and not in the context of the four haplotypes (SR, SG, GR and GG) that
      exist in native beta1-ARs. METHODS: To address this, the function of each of the
      receptor haplotypes was studied in HEK 293 cells stably transfected with
      appropriately modified human beta1-adrenoceptor cDNA sequence. RESULTS: The
      affinity for the beta-adrenoceptor ligand, [125I]-cyanopindolol, was not
      significantly different across the haplotypes, but a high affinity state for the
      beta1-AR could only be demonstrated for receptors carrying the 389R substitution.
      Both basal (GR 36.3 +/- 2.9* vs. SR 16.5 0 +/- 3.6 and GG 31.7 +/- 1.4* vs. SG
      15.6 +/- 1.5 pmol/mg protein; *P < 0.001) and maximal (GR 163 +/- 7.6 vs. SR 124
      +/- 8.1* and GG 75.0 +/- 1.0 vs. SG 52.4 +/- 1.1* pmol/mg protein; *P < 0.001)
      isoprenaline-evoked cAMP production was significantly affected by both
      substitutions. Incubation with isoprenaline (10 microm for 30 min or 20 h) caused
      increased down-regulation of beta1-ARs in cells expressing GG and GR haplotypes
      (at 20 h percentage fall respectively -28.1 +/- 5.2 and -38.2 +/- 3.0).
      CONCLUSIONS: These data highlight important functional differences between the
      common beta1-AR haplotypes and the need for consideration of haplotypes and not
      individual genotypes in determining the in-vivo role of these polymorphisms
      within this important drug target.

PMID- 15247627
TI  - Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not
      involved in chronic pancreatitis.
AB  - OBJECTIVES: Chronic pancreatitis (CP) is associated with alcohol abuse, smoking
      and other dietary or environmental factors. UDP-glucuronosyltransferases (UGTs)
      are phase II detoxifying enzymes responsible for glucuronidation of various
      exogenous and endogenous compounds. Genetic variations, resulting in variable
      rates of glucuronidation, are of toxicological and physiological importance and
      are frequently associated with diseases. Recently, a genetic polymorphism in
      UGT1A7 was possibly associated with an increased risk for CP. We investigated
      whether polymorphisms in the genes for UGT1A1, UGT1A6 and UGT1A8 modified the
      risk for CP. METHODS: DNA samples were obtained from 258 adult CP patients with
      alcoholic (n = 153), hereditary (n = 25) or idiopathic (n = 80) origin. DNA from
      140 healthy controls was analyzed for comparison. Patients and controls were all
      of Caucasian origin. Genetic polymorphisms in UGTs were determined by PCR,
      eventually followed by restriction-fragment-length-polymorphism analyses in all
      subjects. RESULTS: The distribution of the various alleles of UGT1A1, UGT1A6 and
      UGT1A8 did not differ between CP patients and healthy controls. CONCLUSION: These
      data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not
      predispose to the development of CP in Caucasians.

PMID- 15247628
TI  - Polymorphism of human mu class glutathione transferases.
AB  - OBJECTIVES AND METHODS: A combined database mining approach was used to detect
      polymorphisms in the mu class glutathione-S-transferase (GST) genes. Although a
      large number of potential polymorphisms were detected in the five genes that
      comprise the Mu class GSTs using sequence alignment programs and by searching
      single nucleotide polymorphism databases, the majority were not validated or
      detected in three major ethnic populations (African, Southern Chinese and
      Australian European). RESULTS: Two new polymorphisms were detected and
      characterized in the GSTM3 gene. A rare pG147W substitution was detected only in
      the Southern Chinese subjects. A more common pV224I substitution was found in
      each of the ethnic groups studied, and significant differences in allele
      frequencies were observed between each group. These two polymorphisms can combine
      to form four distinct haplotypes (GSTM3A [p.G147;V224], GSTM3C [p.G147;I224],
      GSTM3D [p.W147;V224], GSTM3E [p.W147;I224]). The four isoforms were expressed in
      Escherichia coli and characterized enzymatically with several substrates
      including 1-chloro-2,4-dinitrobenzene (CDNB), cumene hydroperoxide and t-nonenal.
      GSTM3-3 containing the variant p.W147 residue tended to show diminished specific
      activity and catalytic efficiency with CDNB. In contrast, GSTM3-3 containing the
      variant p.I224 residue tended to show increased specific activity and catalytic
      efficiency with CDNB. Interactions between the different p.147 and p.224 residues
      were also observed, with the GSTM3C isoform exhibiting the greatest activity with
      each substrate, and GSTM3E the lowest. CONCLUSION: These functional polymorphisms
      may play a significant role in modulating the ability of GSTM3-3 to metabolize
      substrates such as the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1
      nitrosourea.

PMID- 15247630
TI  - Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human
      heart by hereditary polymorphisms.
AB  - OBJECTIVES: Variable expression of the ABC-type multidrug resistance membrane
      protein P-glycoprotein (P-gp, MDR1, ABCB1) in human heart is a potential
      modulator of drug effects or drug-induced cardiotoxicity. Expression of P-gp is
      known to be affected by single nucleotide polymorphisms in the MDR1 gene.
      Therefore, genotype-dependent expression of P-gp could be an important modulator
      of action of cardiac drugs. METHODS: Heart tissue (auriculum) from 51 patients
      undergoing coronary artery bypass graft surgery was screened for genotype
      dependent P-gp expression. P-gp was identified by immunoblotting and localized
      using immunohistochemistry. MDR1 mRNA was quantified by real-time PCR and
      immunohistochemistry and related to the MDR1 genotypes G2677T/A (Ala893Ser/Thr)
      and C3435T. RESULTS: MDR1/18S rRNA mRNA copy numbers in heart auriculum were 3.48
      +/- 2.25 x 10(-6) compared to 4.56 +/- 0.58 x 10(-6) in non-failing ventricular
      samples studied before. While the exon 26 C3435T genotype did not influence MDR1
      mRNA expression, we found significantly elevated MDR1 mRNA expression in 10
      patients carrying the exon 21 2677 AT or TT genotype as compared to 12 patients
      carrying the GG-variant with intermediate MDR1 mRNA expression in 29 heterozygous
      samples. P-gp was detected in the endothelial wall. Quantitative
      immunohistochemistry of protein expression, however, did not reveal significant
      influence of the studied SNPs. CONCLUSION: The present study based on auricular
      samples suggests that genetic factors play a rather limited role in modulating P
      gp expression in human heart. Therefore, the substantial interindividual
      variability in cardiac P-gp expression is likely related to environmental or
      disease related factors.

PMID- 15247629
TI  - Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6).
AB  - OBJECTIVES: In humans, cytochrome P450 2A6 (CYP2A6) constitutes the principal
      nicotine C-oxidase. Several different polymorphic CYP2A6 gene variants are known
      which contribute to the highly variable expression of this enzyme among
      individuals. In this study we report a novel polymorphism located in the 5'
      flanking region (-745A > G) of the CYP2A6 gene disrupting a CCAAT box. METHODS
      AND RESULTS: Electrophoretic mobility shift assays (EMSA) indicated that NF-YA is
      part of this nuclear protein complex. Chromatin immunoprecipitation revealed that
      NF-Y recognizes a region of the CYP2A6 5' flanking region located between -932
      and -606. EMSA showed that out of the three CCAAT boxes in the CYP2A6 promoter,
      with CCAAT core sequences located between -839/-835, -748/-744, and -689/-685,
      only the one at -748/-744 was able to compete with the nuclear protein complex
      binding to the -748/-744 CCAAT box. Cotransfection experiments indicated that NF
      Y acts as a positive regulatory element on CYP2A6 gene regulation. EMSA
      demonstrated that an NF-Y consensus oligonucleotide but not the -745A > G
      oligonucleotide competed efficiently with binding of the protein complex to the 
      748/-744 CCAAT box. Promoter activity of the -745A > G variant was significantly
      reduced to 78% relative to the wild-type allele in HepG2 cells transfected with
      luciferase reporter plasmids. Finally, haplotype analysis was carried out
      comprising the -745A > G variant in combination with all known CYP2A6 3' and 5'
      flanking single nucleotide polymorphisms: -1013A > G, -48T > G, and the
      CYP2A6/CYP2A7 3' flank conversion. CONCLUSION: A new haplotype, CYP2A6*1H was
      identified, with allele frequencies of 3.1% in Swedish and 5.2% in Turkish
      populations.

PMID- 15247631
TI  - Prediction of successful weight reduction under sibutramine therapy.

PMID- 15247648
TI  - Using ultrafiltration to treat heart failure.

PMID- 15247649
TI  - Measuring gastric residual volume.

PMID- 15247653
TI  - Understanding chronic pain.

PMID- 15247654
TI  - PCA by proxy: Too much of a good thing.

PMID- 15247672
TI  - TIME heals all wounds.

PMID- 15247673
TI  - Nursing2004 needle-stick and sharps-safety survey: getting to the point about
      preventable injuries.

PMID- 15247674
TI  - Nourishing the soul.

PMID- 15247675
TI  - Healing the mind and spirit as the body fails.

PMID- 15247676
TI  - Patient-education guide. Melanoma.

PMID- 15247677
TI  - Caring for a sick child in a nonpediatric setting.

PMID- 15247678
TI  - Understanding cardiomyopathies.

PMID- 15247679
TI  - How to check perfusion lickety split.

PMID- 15247683
TI  - How PDAs can speed up the organ transplant process.

PMID- 15247684
TI  - Viewing the small intestine via capsule endoscopy.

PMID- 15247685
TI  - The scoop on green tea.

PMID- 15247688
TI  - Microbe of the month: Giardia lamblia.

PMID- 15247689
TI  - Missed connections.

PMID- 15247690
TI  - Documenting refusal of treatment.

PMID- 15247691
TI  - Understanding fluids and electrolytes: challenge yourself with this quiz.

PMID- 15247692
TI  - Asystole in a heart transplant recipient.

PMID- 15247696
TI  - The problem with prostatitis. What do we know? What do we need to know?

PMID- 15247697
TI  - Catheters, stents and nephrostomy tubes. Are they necessary and do they work?

PMID- 15247698
TI  - Increased incidence of pathological and clinical prostate cancer with age: age
      related alterations of local immune surveillance.
AB  - PURPOSE: The incidence of prostate cancer dramatically increases with age. The
      etiology still awaits elucidation, and the question as to why it is so
      prominently a disease of aging remains unanswered. We offer an explanation by
      suggesting an age related deficient immune surveillance. MATERIALS AND METHODS:
      Reports published in the scientific literature with relevance to cancer and
      immunity, immune senescence, blood-prostate barrier and immune privilege were
      identified using MEDLINE. RESULTS: The existence of a blood-prostate barrier is a
      fair assumption, and the prostate may be considered an immune privileged site.
      With aging the prostate, a priori immunologically under surveilled, probably
      becomes more and more so. There is impaired function, transmigration and probably
      penetration into the gland of natural killer and other immune competent cells due
      to the onset of immune senescence coupled with impaired diapedesis and possible
      age related alterations in the blood-prostate barrier. CONCLUSIONS: Apparently,
      with aging the immune surveillance of the already immune privileged prostate is
      progressively and further affected. This condition may result in the inability of
      the gland to eradicate emergent malignant cells.

PMID- 15247699
TI  - The molecular genetic basis of mitochondrial malfunction in bladder tissue
      following outlet obstruction.
AB  - PURPOSE: Bladder dysfunction following partial outlet obstruction is a frequent
      consequence of benign prostatic hyperplasia and an increasingly common problem
      given the aging of the general population. Recent studies from this and other
      groups have begun to elucidate the molecular bases for the well described
      physiological malfunctions that characterize this clinical entity. We summarized
      and synthesized that information. MATERIALS AND METHODS: Using modern methods of
      molecular genetics, including real-time polymerase chain reaction, real-time
      reverse transcriptase-polymerase chain reaction and others, as well as
      traditional experimental techniques such as electron microscopy we and others
      examined the transcriptional profile, morphology, etc of bladder smooth muscle
      mitochondria in experimental models of outlet obstruction. RESULTS: Data from
      many studies have demonstrated that aberrant gene expression in the mitochondrial
      and mitochondria related nuclear genetic systems underlies the loss of compliance
      and other attributes of bladder dysfunction following outlet obstruction. Such
      aberrant transcriptional characteristics engender loss of function in the
      electron transport and oxidative phosphorylation systems. Morphological studies
      of mitochondria in the animal model systems support this conclusion. CONCLUSIONS:
      In large part the loss of function in bladder smooth muscle following outlet
      obstruction results from the attenuation of mitochondrial energy production. In
      this article we reviewed and synthesized all available experimental observations
      relevant to this problem and we suggest future lines of inquiry that should prove
      fruitful in developing new strategies to treat the condition.

PMID- 15247700
TI  - Adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in
      children.
AB  - PURPOSE: Many children with urological disease require long-term treatment with
      antibiotics. In many cases the choice of medical instead of surgical management
      hinges on the implied safety of certain drugs. Recently some groups have
      advocated subureteral injection procedures to avoid long-term antibiotics for low
      grade reflux. We present a concise and relevant review on the use and adverse
      reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children.
      MATERIALS AND METHODS: We reviewed the literature regarding the safety and
      toxicity of these drugs. Information regarding absorption, excretion and dosing
      was also gathered to explain better the mechanisms of toxicity. RESULTS: Adverse
      reactions in children reported in the literature related to nitrofurantoin are
      gastrointestinal disturbance (4.4/100 person-years at risk), cutaneous reactions
      (2% to 3%), pulmonary toxicity (9 patients), hepatoxicity (12 patients and 3
      deaths), hematological toxicity (12 patients), neurotoxicity and an increased
      rate of sister chromatid exchanges. Adverse reactions in children related to
      trimethoprim/sulfamethoxazole are almost exclusively due to the sulfamethoxazole
      component, including cutaneous reactions (1.4 to 7.4 events per 100 person-years
      at risk), hematological toxicity (0% to 72% of patients) and hepatotoxicity (5
      patients). The majority of adverse reactions were found in children on full dose
      therapy and not prophylaxis. CONCLUSIONS: The use of nitrofurantoin, trimethoprim
      and sulfamethoxazole is safe in children for long-term prophylactic therapy. The
      antibiotic safety issue should not be misconstrued as an argument for surgical
      therapy, whether minimally invasive or not. Adverse reactions exist to these
      medicines but they are less common than seen in adults, presumably because of the
      lower dose used for therapy, and the lack of significant comorbidities and drug
      interactions in children. Serious side effects are extremely rare and most are
      reversible by discontinuing therapy. The extremely low potential for significant
      adverse reactions should be discussed with parents.

PMID- 15247701
TI  - Tumor capacitance: electrical measurements of renal neoplasia.
AB  - PURPOSE: Studies have demonstrated that biological tissues possess unique
      electrical properties. We evaluate the electrical properties of renal tumors
      using a specialized probe with the capability of measuring intra-tissue
      capacitance in an ex vivo model of fresh surgically excised tissue. MATERIALS AND
      METHODS: An electrical monitoring device was used to measure tissue capacitance
      at a frequency of 1 MHz on 34 ex vivo kidney specimens freshly obtained after
      surgical excision. Tissue capacitance was promptly measured in the excised tumor
      as well as surrounding normal parenchyma and fat. Dielectric permittivity in each
      tissue was calculated using the measured capacitance data. These data were
      compared and correlated to pathological findings. RESULTS: The final pathology on
      the 34 specimens revealed 28 renal cell carcinomas (RCC), 3 oncocytomas and 3
      angiomyolipomas. In patients with RCC dielectric permittivity of tumor tissue was
      1.43 +/- 0.39 times greater than that of surrounding normal parenchyma (p <
      0.001). The average tumor-to-normal tissue dielectric permittivity ratio for RCC
      was significantly greater than that for angiomyolipoma (1.43 +/- 0.39 vs 0.73 +/-
      0.77, p < 0.05) but similar to that for oncocytoma (1.43 +/- 0.39 vs 1.63 +/-
      0.77, p = 0.39). CONCLUSIONS: Tissue capacitance measurements may be used to
      differentiate renal tumor from surrounding normal tissue. In vivo studies will
      ultimately determine the clinical use of this technology in localizing renal
      neoplasms and differentiating between malignant and benign tissues.

PMID- 15247702
TI  - Necessity of ureteral catheter during laparoscopic partial nephrectomy.
AB  - PURPOSE: Laparoscopic partial nephrectomy (LPN) is a relatively recently
      introduced method of treating renal tumors and, as such, surgical technique is
      evolving. In open series urinary fistula formation represents a common
      postoperative complication. In the laparoscopic approach investigators have
      advocated the placement of a ureteral catheter with retrograde dye injection to
      visualize caliceal entry to aid in closure. In this study we assessed the
      necessity of ureteral catheter placement during LPN in decreasing urinary
      leakage. MATERIALS AND METHODS: From February 1998 until November 2002
      laparoscopic partial nephrectomy was performed in 103 patients with renal tumors.
      The patients were assessed retrospectively and divided into 2 groups according to
      placement (group 1) or no placement (group 2) of an external ureteral catheter.
      Group 1 included 54 patients (mean age +/- SD 57.4 +/- 13.4 years) and group 2
      included 49 patients (mean age +/- SD 57.5 +/- 10.9). Intraoperative and
      postoperative parameters including blood loss, operative time, ischemia time,
      mass size, complications and hospital stay were reviewed and compared between the
      2 groups. RESULTS: There were no differences between the 2 groups in mean
      estimated blood loss (group 1, 394.7 cc vs group 2, 291.5 cc, p = 0.07),
      postoperative serum creatinine (group 1, 0.95 mg/dl vs group 2, 0.89 mg/dl, p =
      0.12), requirement for pain medication (group 1, 8.9 mg vs group 2, 4.9 mg
      morphine equivalents, p = 0.12), hospital stay (group 1, 3.1 vs group 2, 2.9, p =
      0.29) and warm ischemia time (group 1, 28 minutes vs group 2, 26.5 minutes, p =
      0.18). Mean total operative time was significantly longer for group 1 compared to
      group 2 (191.1 vs 149.4 minutes, respectively, p = 0.001). Postoperative urinary
      leakage requiring prolonged drainage occurred in 1 patient in group 1 and 1 in
      group 2. In both cases caliceal entry was identified and sutured. CONCLUSIONS:
      With experience caliceal entry can be identified without the need for a ureteral
      catheter in patients undergoing LPN for a tumor less than 4.5 cm. Urinary fistula
      may occur despite caliceal entry and repair. A ureteral catheter may not decrease
      urinary fistula in patients undergoing LPN.

PMID- 15247703
TI  - Laparoscopic nephrectomy, ex vivo excision and autotransplantation for complex
      renal tumors.
AB  - PURPOSE: In many patients partial nephrectomy is the preferred alternative to
      radical nephrectomy for upper urinary tract cancers. We describe the use of
      laparoscopic nephrectomy, ex vivo excision and reconstruction, and
      autotransplantation to expand the realm of minimally invasive, nephron sparing
      surgery to the most complex renal tumors. MATERIALS AND METHODS: In our cohort
      undergoing renal surgery 2 patients had a solitary kidney with renal tumors not
      considered amenable to in situ partial nephrectomy. After transperitoneal
      laparoscopic nephrectomy ex vivo tumor excision and renorrhaphy were performed.
      The kidney was transplanted to the ipsilateral iliac vessels through the Gibson
      extraction incision. RESULTS: Indications for surgery were high grade urothelial
      carcinoma within a caliceal diverticulum and a central 5 cm renal cell carcinoma.
      Mean nephrectomy, cold ischemic and transplantation times were 4.5, 2 and 3.7
      hours, respectively. No intraoperative or postoperative complications were noted.
      Hospitalization was 12 and 6 days, respectively. At 20 and 12 months of followup
      each patient remained off dialysis without evidence of recurrence. CONCLUSIONS:
      Despite experience with conventional nephron sparing surgery some cases may be
      more appropriate for ex vivo excision and reconstruction. In these situations the
      minimally invasive approach provides a kidney suitable for renal
      autotransplantation, while simultaneously decreasing patient morbidity. This
      novel approach to complex renal tumors is feasible when one applies principles of
      laparoscopic donor nephrectomy and possesses experience with renal
      transplantation.

PMID- 15247704
TI  - A protocol for performing extended lymph node dissection using primary tumor
      pathological features for patients treated with radical nephrectomy for clear
      cell renal cell carcinoma.
AB  - PURPOSE: We determined the primary pathological features of clear cell renal cell
      carcinoma that are predictive of positive regional lymph nodes at radical
      nephrectomy (RN) and developed a protocol for the selective use of extended lymph
      node dissection. MATERIALS AND METHODS: We studied 1,652 patients who underwent
      RN for unilateral pM0 sporadic clear cell renal cell carcinoma between 1970 and
      2000. A multivariate logistic regression model was used to determine the
      pathological features of the primary tumor that were associated with positive
      regional lymph nodes at RN. RESULTS: There were 887 (54%) patients with no
      positive nodes (pN0), 57 (3%) with 1 positive node (pN1), 11 (1%) with 2 or more
      positive nodes (pN2) and 697 (42%) who did not have any lymph nodes dissected
      (pNx). Nuclear grade 3 or 4 (p <0.001), presence of a sarcomatoid component (p
      <0.001), tumor size 10 cm or greater (p = 0.005), tumor stage pT3 or pT4 (p =
      0.017) and histological tumor necrosis (p = 0.051) were significantly associated
      with positive regional lymph nodes in a multivariate setting. These features can
      be used to identify candidates for extended lymph node dissection at the time of
      RN. For example, only 6 (0.6%) of the 1,031 patients with 0 or 1 of these
      features had positive lymph nodes at RN compared with 62 (10%) of the 621
      patients with at least 2 of these features. CONCLUSIONS: The primary tumor
      pathological features of nuclear grade, sarcomatoid component, tumor size, stage
      and presence of tumor necrosis can be used to predict patients at the greatest
      risk for regional lymph node involvement at RN.

PMID- 15247705
TI  - Low clinical stage renal cell carcinoma: relevance of microvascular tumor
      invasion as a prognostic parameter.
AB  - PURPOSE: Renal cell carcinoma is a tumor with unpredictable behavior and defining
      reliable prognostic factors would be extremely valuable in the clinical setting.
      Tumor stage, nuclear grade and tumor cell type are the main prognostic clinical
      parameters available. In this study we evaluated the role of microvascular
      involvement in the primary lesion for predicting tumor behavior in patients with
      low stage clinical disease. MATERIALS AND METHODS: A total of 95 patients with
      clinically localized renal cell carcinoma (stages T1-T2 Nx M0) underwent radical
      nephrectomy and/or nephron sparing surgery, and were followed for a median of 45
      months. The impact of microvascular tumor invasion on disease progression and its
      correlation with known pathological outcomes (tumor size, nuclear grade and cell
      type) were studied. RESULTS: Microvascular tumor invasion was observed in 24
      patients (25%), of whom 50% had disease recurrence. Of the 71 patients without
      microvascular invasion only 4 (6%) showed tumor recurrence. When microvascular
      invasion was correlated with other histological parameters, a significant
      statistical association was noted with tumor diameter, perirenal fat invasion,
      macroscopic extension to the renal vein, nuclear grade, lymph node metastasis and
      sarcomatous elements in the tumor. Multivariate analysis showed that
      microvascular invasion and the involvement of regional lymph nodes were
      independent predictors of disease recurrence. Concerning cancer specific
      survival, microvascular invasion and perirenal fat infiltration were the only
      factors related to death. CONCLUSIONS: Microvascular invasion is an independent
      and relevant clinical prognostic parameter for low clinical stage renal cell
      carcinoma.

PMID- 15247706
TI  - Involvement of bone morphogenetic protein 2 in ossification of renal cell
      carcinoma.

PMID- 15247707
TI  - Renal infarction secondary to infiltrative transitional cell carcinoma.

PMID- 15247708
TI  - A referral center's experience with transitional cell carcinoma misdiagnosed as
      interstitial cystitis.
AB  - PURPOSE: There has been a recent trend to diagnose interstitial cystitis (IC) in
      a noninvasive way using a potassium sensitivity test, and a pelvic pain, urgency
      and frequency questionnaire. The concern is that significant pathology causing
      the bladder symptoms may be missed, such as transitional cell carcinoma. We
      present our experience with patients "labeled" as having IC who truly had cancer
      as the cause of irritative symptoms. MATERIALS AND METHODS: A retrospective
      review of patient records at our IC center was performed from 1998 to 2002. A
      total of 600 patients were seen at that time with the diagnosis of interstitial
      cystitis. RESULTS: Six patients (1%) previously diagnosed as having IC were found
      to have transitional cell carcinoma as the cause of symptoms, 4 of whom (67%) had
      no hematuria. Mean time from the diagnosis of IC to diagnosis of transitional
      cell carcinoma was 29.8 months. Irritative bladder symptoms resolved after
      identifying and treating the malignancy. CONCLUSIONS: Patients with irritative
      voiding symptoms require a thorough evaluation which may include cystoscopy,
      cytology and upper tract imaging. Hematuria was not a good predictor of cancer in
      our series. In the era before widespread use of minimally invasive means to
      diagnose IC (ie potassium sensitivity test, pelvic pain, urgency and frequency
      questionnaire) 1% of patients who were considered to have IC actually had
      transitional cell cancer as the cause of symptoms. One would expect that this
      number would increase if the criteria to diagnose IC and initiate treatment were
      oversimplified. Interstitial cystitis remains a diagnosis of exclusion.

PMID- 15247709
TI  - Evidence supporting preoperative chemotherapy for small cell carcinoma of the
      bladder: a retrospective review of the M. D. Anderson cancer experience.
AB  - PURPOSE: Neuroendocrine tumors of the bladder comprise a small subset of all
      bladder tumors. To improve our understanding of this tumor and define outcomes
      with current management, we performed a retrospective review of these cases.
      MATERIALS AND METHODS: We reviewed the records of 88 patients with small cell
      bladder carcinoma evaluated at our institution between 1985 and 2002. Of these
      patients 46 underwent cystectomy, including 25 who were treated with initial
      cystectomy and 21 who received preoperative chemotherapy. RESULTS: For patients
      treated with initial cystectomy median cancer specific survival (CSS) was 23
      months, with 36% disease-free at 5 years. For patients receiving preoperative
      chemotherapy median CSS has not been reached (p = 0.026), although CSS at 5-years
      was 78% with no cancer related deaths observed beyond 2 years. Notably 7 of 25
      patients treated with initial cystectomy received chemotherapy after surgery but
      their survival was no better than those treated with cystectomy alone. As others
      have observed, the pathological stage was higher than clinically appreciated for
      56% of patients treated with initial cystectomy. Moreover, there were no cancer
      related deaths among patients with disease down staged to pT2 or less.
      CONCLUSIONS: Like other neuroendocrine tumors, small cell carcinoma of the
      bladder grows rapidly but is chemo-sensitive. Clinical under staging is the rule.
      Optimal results are achieved via integration of local and systemic treatment. Our
      results suggest that preoperative chemotherapy is the optimal strategy, even in
      the setting of clinically localized cancer. On the basis of these observations,
      we have initiated a trial in which 4 cycles of aggressive multiagent preoperative
      chemotherapy are followed by radical cystectomy.

PMID- 15247710
TI  - Phase I pharmacokinetic study of a single intravesical instillation of
      gemcitabine administered immediately after transurethral resection plus multiple
      random biopsies in patients with superficial bladder cancer.
AB  - PURPOSE: In this phase I study we determined the pharmacokinetic and toxicity
      profiles of a single intravesical instillation of gemcitabine administered
      immediately after complete transurethral resection (TUR) plus multiple random
      biopsies. MATERIALS AND METHODS: Ten patients with superficial bladder cancer
      clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose
      of gemcitabine was administered intra-vesically immediately after TUR plus 6
      random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted
      in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of
      gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high
      pressure liquid chromatography assay. RESULTS: Treatment was clinically well
      tolerated in all patients. Two patients in the 1,500 mg group had minimal
      hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms.
      There was no remarkable systemic toxicity on hematology or biochemistry at any
      dose level on day 12 or 30. One patient per dose level showed tumor recurrence on
      3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8
      microg/ml and the mean last AUC was 158 microg/ml*minute. There was large
      interpatient variability but no significant differences between the 2 dose
      levels. CONCLUSIONS: Single intravesical instillation of gemcitabine immediately
      after TUR and multiple random biopsies for superficial bladder cancer are a safe
      and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles
      of intravesical gemcitabine support future phase II studies with this agent.

PMID- 15247711
TI  - Laparoscopic assisted radical cystectomy with ileal neobladder: a comparison with
      the open approach.
AB  - PURPOSE: To date, there have been only a few reports regarding the feasibility of
      the laparoscopic approach to radical cystectomy. In none of these cases has the
      laparoscopic approach been contrasted with a contemporary cohort of open
      cystectomy and diversion. Recently, we initiated laparoscopic assisted radical
      cystoprostatectomy and ileal neobladder (LACINB) wherein the cystoprostatectomy
      and pelvic lymph node dissections are performed laparoscopically and the
      reconstructive portion is performed via a 15 cm Pfannenstiel incision. We present
      and compare our initial series of LACINB with radical cystectomy performed by the
      open approach (OCINB) during the same period. MATERIALS AND METHODS: Between
      September 2001 and February 2003, 13 men underwent LACINB and 11 underwent OCINB
      at our institution. RESULTS: There was no statistically significant difference in
      operative time, blood loss or complication rates between the LACINB and OCINB
      groups. However, postoperative analgesic use was significantly less in the LACINB
      group. Time to start of a liquid diet, solid diet and length of hospitalization
      were also significantly less in the LACINB group vs the OCINB group. All margins
      in both groups were negative for bladder cancer, although 1 patient in the LACINB
      group had an incidentally found prostate cancer with a positive apical margin.
      CONCLUSIONS: LACINB is a feasible and reproducible procedure, which results in
      decreased postoperative pain and quicker recovery without a significant increase
      in operative time. However, longer followup is needed to assess long-term
      oncological and functional outcomes.

PMID- 15247712
TI  - Complications of inguinal and pelvic lymphadenectomy for squamous cell carcinoma
      of the penis: a contemporary series.
AB  - PURPOSE: We examined complications in a contemporary population of patients with
      penile cancer undergoing inguinal lymphadenectomy with or without pelvic
      lymphadenectomy. MATERIALS AND METHODS: The records of all patients treated for
      squamous cell carcinoma of the penis from January 1992 to May 2003 were reviewed.
      Complications and length of stay were examined. Complications were divided into
      early (30 days or less after surgery) and late (greater than 30 days). RESULTS: A
      total of 41 men were diagnosed with squamous cell carcinoma of the penis, of whom
      22 underwent a total of 40 inguinal lymphadenectomies (ILs). Of the patients 13
      underwent unilateral IL, 9 underwent simultaneous bilateral ILs and 10 underwent
      pelvic lymphadenectomy. Mean followup was 34.2 months (range 9.2 to 69.3). Early
      complications were lymphedema in 4 of 40 cases (10%), minor wound infection in 3
      (7.5%) and minor wound separation in 3 (7.5%). Additionally, 5 of 40 patients
      (12.5%) had lymphoceles, which spontaneously resolved. Late complications were
      lymphedema in 2 of 40 patients (5%), flap necrosis in 1 (2.5%) and lymphocele in
      1 (2.5%), requiring percutaneous drainage. There was no significant difference in
      the complication rates in patients with unilateral dissection compared to
      bilateral or pelvic lymph node dissection. Median length of stay was 2 days
      (range 1 to 9). There was no significant difference in hospital stay for
      unilateral dissection compared to bilateral or pelvic lymph node dissection.
      CONCLUSIONS: These data demonstrate the relative safety of a contemporary
      lymphadenectomy. We believe that these results lend support to early
      lymphadenectomy, including simultaneous bilateral dissections, when clinically
      indicated. Furthermore, these results demonstrate the benefits of a standard
      postoperative pathway using compression stockings, sequential compression devices
      and early ambulation with restricted anticoagulant use.

PMID- 15247713
TI  - Long-term followup of penile carcinoma treated with penectomy and bilateral
      modified inguinal lymphadenectomy.
AB  - PURPOSE: We evaluated modified inguinal lymphadenectomy in the treatment of
      penile carcinoma, analyzing the rate of complications compared to complete
      inguinal lymphadenectomy, the complications in performing lymphadenectomy and
      penectomy concomitantly, and the long-term locoregional recurrence rate.
      MATERIALS AND METHODS: A total of 26 patients with squamous cell carcinoma of the
      penis were clinically assessed, and underwent penectomy and bilateral modified
      inguinal lymphadenectomy at the same operative time. Frozen section analysis of
      lymph nodes was performed and if metastases were detected a complete ipsilateral
      inguinal dissection was performed. RESULTS: A total of 52 modified
      lymphadenectomies were performed. In 10 procedures lymph node metastasis was
      present. Clinical staging presented false-positive and false-negative rates of
      50% and 7.9%, respectively. The complication rate for modified lymphadenectomy
      was 38.9% and for complete inguinal lymphadenectomy it was 87.5%. Followup ranged
      from 5 to 112 months and mean followup of recurrence-free cases was 78 months
      (range 38 to 112). A total of 18 patients underwent bilateral negative modified
      inguinal lymphadenectomy and 2 of these experienced locoregional recurrence
      within 2 years after surgery. CONCLUSIONS: Modified inguinal lymphadenectomy
      causes a lower complication rate than complete inguinal lymphadenectomy.
      Bilateral modified inguinal lymphadenectomy performed at the same time as
      penectomy does not increase the complication rate. When frozen section analysis
      is negative bilaterally, 5.5% of inguinal regions might still harbor occult
      metastasis. Modified inguinal lymphadenectomy is recommended as a staging
      procedure in all patients with T2-3 penile carcinoma. A straight followup is
      required for 2 years since all recurrence was within this period.

PMID- 15247714
TI  - Comparison of 3 different methods of anesthesia before transrectal prostate
      biopsy: a prospective randomized trial.
AB  - PURPOSE: Periprostatic nerve block (PNB) is the most common anesthesia technique
      used before prostate biopsy. However, needle punctures for anesthetic
      infiltration may be painful and cause higher infectious complications. We
      assessed whether addition of rectal lidocaine gel would improve its efficacy. We
      also investigated the efficacy and safety of tramadol, a codeine derivative, as a
      noninvasive method. MATERIALS AND METHODS: A total of 300 patients who underwent
      prostate biopsies were randomized into 4 groups of controls, PNB,
      perianal/intrarectal lidocaine gel plus PNB and tramadol. Pain was assessed with
      a numeric analog scale. RESULTS: Each group consisted of 75 patients, and there
      was a statistically significant difference among pain scores (p = 0.001). Mean
      pain scores were 4.63 for controls, 2.57 for PNB, 2.03 for infiltration plus gel
      group and 3.11 for tramadol. Pain and discomfort were least in PNB plus gel arm.
      The difference of pain score between PNB alone and tramadol group did not reach
      statistical significance. Infectious complications were higher in the combination
      group, whereas there were no complications with tramadol. CONCLUSIONS: Any form
      of analgesia/anesthesia was superior to none. The combination of PNB plus gel
      provided significantly better analgesia compared to PNB alone or tramadol. If
      this can be duplicated in other trials, the combination may be accepted as the
      new gold standard of anesthesia for prostate biopsy. The efficacy of tramadol was
      similar to that of PNB, and was free of complications. Therefore, tramadol may
      have a role before prostate biopsy, which needs to be explored.

PMID- 15247715
TI  - Kruppel-like factor 6 germ-line mutations are infrequent in Finnish hereditary
      prostate cancer.
AB  - PURPOSE: Recently, Kruppel-like factor 6 gene (KLF6) has been shown to be
      inactivated in up to 77% of prostate carcinomas. KLF6 has an important role in
      regulating cell growth and differentiation. The function and high mutation
      frequency in sporadic prostate carcinomas make KLF6 an attractive candidate for
      prostate cancer predisposition and, therefore, DNA samples from 69 Finnish
      prostate cancer families were analyzed for KLF6 mutations. MATERIALS AND METHODS:
      DNA samples from 69 Finnish prostate cancer families were screened for mutations
      in the KLF6 gene using single-strand conformation polymorphism analysis and
      confirmatory sequencing. RESULTS: In 8 (11.6%) families single-strand
      conformation polymorphism shifts were present. Sequencing revealed 6 201G>A
      (R201R) polymorphisms, as well as a -4C>A and a 956T>C alteration in the 5'- and
      3'-untranslated regions, respectively. Nonsense or missense mutations were not
      found. CONCLUSIONS: Our data suggest that KLF6 germ-line mutations are of
      marginal importance in prostate cancer predisposition in Finland.

PMID- 15247716
TI  - Is tumor volume an independent prognostic factor in clinically localized prostate
      cancer?
AB  - PURPOSE: There continues to be debate regarding the prognostic significance of
      tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the
      prognostic significance of TV in a large series of patients followed for a long
      time to discover whether the effect of TV has changed with earlier detection of
      smaller tumors. MATERIALS AND METHODS: TV was measured planimetrically in 1,302
      consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to
      2000. We correlated TV with standard clinical and pathological features, and
      determined the prostate specific antigen nonprogression rate. Median followup was
      46 months (range 1 to 202). RESULTS: TV was weakly associated with other clinical
      and pathological features. Median TV decreased significantly over time (2.16 cm3
      before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found
      within each clinical stage. In univariate analysis TV correlated strongly with
      the probability of progression. However, in multivariate analysis TV was not a
      significant independent predictor of prognosis, either in the whole cohort of
      patients or in those with peripheral zone cancer only. Even in univariate
      analysis TV had no effect on prognosis for patients in whom cancer was either
      confined to the prostate or was Gleason score 2 through 6. CONCLUSIONS: TV
      provides no independent prognostic information when considered in multivariate
      analysis with Gleason score and pathological stage. Measurement of TV before
      treatment is less likely to characterize prostate cancer accurately than
      assessment of tumor grade and extent. There seems to be little reason to measure
      TV routinely in RP specimens.

PMID- 15247717
TI  - Contemporary impact of transrectal ultrasound lesions for prostate cancer
      detection.
AB  - PURPOSE: Transrectal ultrasound (TRUS) guided systematic biopsy of the prostate
      is the gold standard diagnostic modality for prostate cancer. Consequently, the
      value of discrete hypoechoic lesions on TRUS lesions considered suspicious for
      cancer deserves meticulous reevaluation, specifically in the prostate specific
      antigen era when the majority of tumors diagnosed are nonpalpable. We studied
      whether the predictability of a biopsy core changes if the tissue comes from an
      isoechoic vs hypoechoic lesion. MATERIALS AND METHODS: Prospective data were
      collected on 3,912 consecutive patients referred to our medical center between
      1993 and 1999 for biopsy of the prostate. A sextant technique (apex, mid gland
      and base) with an additional core biopsy from the transitional zone was used. If
      a hypoechoic lesion was identified, the biopsy was taken from the lesion.
      Correlation between hypoechoic lesions, isoechoic areas and cancer detection for
      each core was performed. RESULTS: A total of 31,296 cores were obtained from the
      cohort. Overall 2,642 (68%) cores had at least 1 hypoechoic lesion
      ultrasonographically. Cancer was detected in 675 (25.5%) and 323 (25.4%) patients
      with or without hypoechoic lesions (p = 0.97). The per core cancer detection was
      fairly uniform and averaged 9.3% and 10.4% for hypoechoic and isoechoic areas,
      respectively. The difference was not statistically significant (p = 0.3). Gleason
      scores were less than 7, 7 and greater than 7 in 46%, 34% and 20% of cases,
      respectively. CONCLUSIONS: Despite the higher prevalence of cancers discovered in
      prostates with hypoechoic areas, the hypoechoic lesion itself was not associated
      with increased cancer prevalence compared with biopsy cores from isoechoic areas.
      For impalpable tumors TRUS findings are not contributory for staging.

PMID- 15247718
TI  - Bowel function and bother after treatment for early stage prostate cancer: a
      longitudinal quality of life analysis from CaPSURE.
AB  - PURPOSE: We measured bowel function and bowel bother longitudinally the first 2
      years after treatment for early stage prostate cancer. MATERIALS AND METHODS: We
      studied bowel function and bother in 1,584 men recently diagnosed with early
      stage prostate cancer and followed for 2 years after radical prostatectomy,
      external beam radiation or brachytherapy. Principal outcomes were assessed with
      the UCLA Prostate Cancer Index, a validated instrument that includes these 2
      domains. Multivariate analyses were conducted to ascertain significant predictors
      of bowel function and bother. Subjects were drawn from Cancer of the Prostate
      Strategic Urologic Research Endeavor (CaPSURE, TAP Pharmaceutical Products, Inc.,
      Lake Forest, Illinois), a national, longitudinal registry of men with prostate
      cancer. RESULTS: Men treated with external beam radiation or brachytherapy
      suffered worse bowel function and were more bothered by it than men treated
      surgically. After an initial period of posttreatment impairment, all 3 groups
      demonstrated improvement with time in both domains, although bowel bother
      persisted longer in men treated with external beam radiation. Surgery patients
      reached a steady state by 3 months, while those treated with external beam
      radiation or brachytherapy continued to improve for more than a year after
      treatment. Older men were more bothered by bowel dysfunction than younger men.
      Ethnicity, comorbidity and education did not affect either bowel function or
      bother. CONCLUSIONS: Patients undergoing surgery, external beam radiation or
      brachytherapy have different longitudinal profiles of bowel function and bother
      during the first 2 years after treatment. Bowel function and bother are worse
      after external beam radiation but they are also impaired after brachytherapy. Men
      choosing surgery experience transient impairment in the bowel domains. This
      information may be useful to patients making treatment decisions for early stage
      prostate cancer.

PMID- 15247719
TI  - Obesity and biochemical outcome following radical prostatectomy for organ
      confined disease with negative surgical margins.
AB  - PURPOSE: We have previously shown that men with a body mass index (BMI) greater
      than 35 kg/m2 had higher rates of positive surgical margins and significantly
      higher biochemical recurrence rates following radical prostatectomy (RP). To
      determine whether the higher prostate specific antigen (PSA) recurrence rates
      were due solely to the higher positive margin rate, we examined whether obesity
      was an independent predictor of biochemical failure among men with negative
      surgical margins. MATERIALS AND METHODS: We examined data from 1,250 men treated
      with RP between 1988 and 2003 at 5 equal access medical centers, of whom 731 had
      pathologically organ confined disease and negative surgical margins. Multivariate
      Cox proportional hazards analysis was used to determine if BMI was a significant
      independent predictor of biochemical recurrence. RESULTS: Mean BMI significantly
      increased over time (p = 0.010). Black men were significantly more likely to be
      obese than white or nonwhite-nonblack men. After controlling for all preoperative
      characteristics, body mass index was a significant predictor of biochemical
      failure with moderately and severely obese men (BMI 35 kg/m2 or greater) having
      greater than a 4-fold increased risk of PSA failure (p = 0.035). After
      controlling for the higher pathological Gleason grades among obese men, body mass
      index remained a significant predictor of biochemical failure with moderately and
      severely obese men (BMI 35 kg/m2 or greater) having nearly a 4-fold increased
      risk for PSA failure (p = 0.036). CONCLUSIONS: BMI 35 kg/m2 or greater was
      associated with higher grade tumors and worse outcome following RP in a cohort of
      men with favorable pathological findings. Thus, surgical technique (margin
      status) cannot fully explain the worse outcomes among obese men, suggesting that
      obesity may be associated with a biologically more aggressive form of prostate
      cancer.

PMID- 15247720
TI  - Failure after primary radiation or surgery for prostate cancer: differences in
      response to androgen ablation.
AB  - PURPOSE: Androgen ablation is the standard treatment for recurrent and metastatic
      prostate cancer. Surprisingly few studies have documented the specific results
      for local and distant failure in patients treated primarily with radiation or
      radical prostatectomy. We report the long-term outcome of a series of those
      patients. MATERIALS AND METHODS: We followed until death 94 patients in whom
      primary radiation therapy failed and 67 in whom radical prostatectomy failed. All
      patients received androgen ablation. RESULTS: Statistically (p = 0.04) more
      patients in the radiation group (78%) died of prostate cancer than in the radical
      prostatectomy group (63%). Of the radiation group with local failure alone 63%,
      died of prostate cancer at a median of 5.03 years. Of the surgery group with
      isolated local failure 50% died of cancer at a median of 9.83 years. Of the
      patients treated with radiation with distant metastasis 93% died of cancer with a
      median time to death of 2.34 years. Of the patients treated with surgery 69% died
      of prostate cancer at a median of 3.27 years. The differences in survival between
      the 2 groups was significant. CONCLUSIONS: This study is unique in providing
      followup until death of patients treated with radical prostatectomy and radiation
      who had clinical failure and were treated with androgen ablation. Compelling is
      the finding that survival after androgen ablation after surgical failure is
      superior to that for radiation. If confirmed, this would be a significant
      consideration for future studies of patients in whom primary therapy fails.

PMID- 15247721
TI  - Osteoporosis and spinal fractures in men with prostate cancer: risk factors and
      effects of androgen deprivation therapy.
AB  - PURPOSE: We determined the risk factors for osteoporosis and spinal fractures in
      men with prostate cancer receiving androgen deprivation therapy. MATERIALS AND
      METHODS: We performed a retrospective analysis of 87 consecutive men with
      prostate cancer receiving androgen deprivation therapy referred for evaluation of
      osteoporosis. Data were comprised of lateral thoracolumbar radiographs, bone
      densitometry, serum biochemistry and a detailed assessment of osteoporotic risk
      factors. Multivariate regression analysis was used to determine the major risk
      factors for osteoporosis and spinal fractures. RESULTS: There were 38 (44%) men
      who were 74.5 years old with radiographic evidence of spinal fractures. They had
      an initial mean prostate specific antigen of 52.8 ng/ml and had received androgen
      deprivation therapy for a mean of 39.6 months (95% confidence interval 28.7 to
      50.4). Mean spinal (quantitative computerized tomography t-score -4.2) and
      femoral neck bone mineral densities (dual energy x-ray absorptiometry t-score 
      2.1) were significantly lower than in men without spinal fractures (p < 0.001 for
      all measurements). In the regression analysis the duration of androgen
      deprivation therapy (p = 0.002), serum 25-hydroxyvitamin D levels (p = 0.003) and
      a history of alcohol excess (defined as more than 4 standard drinks daily, p =
      0.04) were the main determinants of spinal fractures. CONCLUSIONS: Prolonged
      androgen deprivation therapy, low serum 25-hydroxyvitamin D levels and a history
      of alcohol excess are important risk factors for osteoporosis and spinal
      fractures in men with prostate cancer.

PMID- 15247722
TI  - A prospective, randomized, placebo controlled, double-blind study of
      amitriptyline for the treatment of interstitial cystitis.
AB  - PURPOSE: We conducted a prospective study to examine the safety and efficacy of
      the tricyclic antidepressant amitriptyline in patients with interstitial cystitis
      (IC). MATERIALS AND METHODS: The study comprised 44 women and 6 men who all met
      the symptom criteria of the National Institute of Diabetes, Digestive and Kidney
      Diseases for IC. The patients were randomly assigned to amitriptyline or placebo.
      Patients were prospectively treated for 4 months with a self-titration protocol
      that allowed them to escalate drug dosage in 25 mg increments in 1 week-intervals
      (maximum dosage 100 mg). The change from baseline in the O'Leary-Sant IC symptom
      and problem index was the primary outcome parameter. Changes in functional
      bladder capacity and frequency (48-hour voiding log), and intensity of pain and
      urgency (visual analog scales) were chosen as secondary outcome parameters.
      RESULTS: Two patients (1 on amitriptyline, 1 on placebo) dropped out of the study
      due to side effects. Thus, the data of 48 patients (24 patients in each group)
      were available for evaluation. Mean symptom score decreased from 26.9 to 18.5 in
      the amitriptyline group compared with 27.6 to 24.1 in the placebo group (p =
      0.005). Pain and urgency intensity improved statistically significantly in the
      amitriptyline group compared with the placebo group (p <0.001). The frequency and
      functional bladder capacity improved to a much greater degree in the
      amitriptyline group but the differences were not statistically significant (p =
      0.063, p = 0.083). Anticholinergic side effects were reported by all except 2
      patients in the amitriptyline group (92%) and by 5 patients in the placebo group
      (21%). Mouth dryness was the most frequent side effect reported in the
      amitriptyline group (79%). CONCLUSIONS: Amitriptyline therapy for 4 months is
      safe and effective for treating IC. A statistically significant change in the
      symptom score and statistically significant improvement of pain and urgency
      intensity compared with placebo were observed. Anticholinergic side effects
      constitute the major drawback of amitriptyline treatment for IC.

PMID- 15247723
TI  - Hypersensitivity reaction associated with intravesical bacillus Calmette-Guerin
      for interstitial cystitis.

PMID- 15247724
TI  - Prognosis of patients with new prostatitis/pelvic pain syndrome episodes.
AB  - PURPOSE: Little is known about the natural history of nonbacterial
      prostatitis/male pelvic pain syndrome, the transition from acute to chronic
      pelvic pain and risk factors for chronicity. In this study we determined the
      course of symptoms after physician visits for new nonbacterial prostatitis/pelvic
      pain syndrome episodes, and determined predictors of symptom persistence 1 year
      later. MATERIALS AND METHODS: A total of 286 male health maintenance organization
      enrollees (87% white, mean age 46.7 years, 83% completed the 12-month followup)
      with recent physician visits for new prostatitis/pelvic pain episodes completed
      baseline, and 3, 6 and 12-month followup telephone interviews, including the
      National Institutes of Health Chronic Prostatitis Symptom Index in a prospective
      longitudinal inception cohort study. RESULTS: On average symptoms improved
      substantially during months 1 to 3, modestly from months 3 to 6 and then remained
      unchanged. At each followup outcomes were better for men whose initial visit was
      for a first lifetime episode compared with a recurrent prostatitis/pelvic pain
      episode. Patients with more severe symptoms (Wald chi-square 11.27, p = 0.0008)
      and whose episode was recurrent (OR 2.2, 95% CI 1.16 to 4.06) at baseline were
      significantly more likely to report symptoms 1 year later. CONCLUSIONS: Most men
      who make physician visits for new nonbacterial prostatitis/pelvic pain episodes
      experience symptom improvement during the next 6 months. However, chronic, mild,
      persistent or recurrent symptoms are common. Patients with previous episodes and
      more severe symptoms are at higher risk for chronic pelvic pain.

PMID- 15247725
TI  - Impact of post-ejaculatory pain in men with category III chronic
      prostatitis/chronic pelvic pain syndrome.
AB  - PURPOSE: Chronic Pelvic Pain Syndrome (CPPS) is a common debilitating condition
      in which ejaculation relieves symptoms for some but exacerbates them in others.
      We studied ejaculatory pain in a cohort with CPPS to investigate associations
      with symptoms, quality of life and risk factors. MATERIALS AND METHODS: The 486
      men in the National Institutes of Health Chronic Prostatitis Cohort study were
      stratified into 4 subgroups according to the presence of ejaculatory pain at
      baseline visit and at each of 3 monthly followup contacts. Subgroups were based
      on answers and labeled NO (always "no"), Nvar ("no" at baseline but "yes" or
      missing at least once), Yvar ("yes" at baseline but "no" or missing at least
      once) and YES (always "yes"). Demographic and quality of life data were obtained
      at baseline, together with medical and sexual history, symptoms, and cultures and
      microscopy of urine and seminal fluids. Associations among selected baseline risk
      factors, symptoms and post-ejaculatory pain were analyzed. RESULTS: Overall 128
      men were classified as NO, 106 as Nvar, 137 as Yvar and 115 as YES. There was a
      progressive increase in baseline National Institutes of Health-Chronic
      Prostatitis Symptom Index total score (modified to exclude post-ejaculatory pain)
      from 18.5 for the NO subgroup to 25.5 for the YES subgroup (p <0.0001). Mental
      and physical quality of life were also progressively lower from the NO to the YES
      subgroup (p <0.001). There were no significant differences in white blood cell
      count or bacterial growth in urine, prostate fluid or semen among subgroups. Men
      in the YES subgroup were younger, more likely to live alone, had lower income and
      a greater variety of sexual practices than those without ejaculatory pain (NO
      subgroup). CONCLUSIONS: Patients with CPPS and persistent ejaculatory pain have
      more severe symptoms, are less likely to improve with time, and have differences
      in demographic and sexual history compared to other patients with CPPS.

PMID- 15247726
TI  - Intravesical potassium chloride sensitivity test in men with chronic pelvic pain
      syndrome.
AB  - PURPOSE: Intravesical potassium chloride has been reported to cause pain in
      patients with interstitial cystitis and male chronic prostatitis (CP)/chronic
      pelvic pain syndrome (CPPS). We performed the potassium chloride sensitivity test
      (PST) in subjects with CP/CPPS and healthy men without pelvic pain. MATERIALS AND
      METHODS: We recruited 40 men with CP/CPPS and 63 healthy men. The National
      Institutes of Health CPPS symptom index was used to measure the severity of
      symptoms. We instilled 100 ml physiological saline (NaCl 0.9%) intravesically.
      The bladder was emptied and 100 ml potassium chloride solution (KCl 40 mEq) were
      instilled. The subjects were asked to score urgency (0 to 10) and pain (0 to 10)
      sensations after each instillation. A positive PST was defined by 5 different cut
      off points as the difference in score between KCl and NaCl instillations.
      Logistic regression analyses and area under the receiver operating
      characteristics curve were used to determine the predictive power of PST in
      CP/CPPS. RESULTS: There was no difference in pain and urgency scores between the
      men with CP/CPPS and controls (p >0.05 for each). Men with CP/CPPS had higher
      pain and urgency scores with KCl than with NaCl (p = 0.011 and 0.033,
      respectively). The rates of positive PST were 50% and 36.5% in the CP/CPPS and
      control groups, respectively (p = 0.160). There was no significant correlation of
      potassium chloride sensitivity scores with National Institutes of Health symptom
      scores (p >0.05 for each). The sensitivity, specificity, and positive predictive
      and negative predictive values of PST were 50%, 63.5%, 46.5% and 66.7%,
      respectively. CONCLUSIONS: Although there was a significant increase in pain and
      urgency scores following KCl instillation in patients with CP/CPPS, these scores
      and the rate of positive PST were not statistically different from those of
      healthy subjects. Thus, PST does not have a good predictive value in the
      diagnosis of CP/CPPS.

PMID- 15247727
TI  - Failure of a monotherapy strategy for difficult chronic prostatitis/chronic
      pelvic pain syndrome.
AB  - PURPOSE: We determined the effect of a best evidence based monotherapeutic
      strategy for patients diagnosed with chronic prostatitis/chronic pelvic pain
      syndrome (CP/CPPS) referred to a specialized prostatitis clinic. MATERIALS AND
      METHODS: Patients with CP/CPPS referred by urologists after failure of prescribed
      therapy for evaluation and treatment at Queen's University prostatitis research
      clinic were extensively evaluated, aggressively treated following a standardized
      treatment algorithm and followed for 1 year using a validated prostatitis
      specific symptom and quality of life instrument, the National Institutes of
      Health Chronic Prostatitis Symptom Index (NIH-CPSI). All patients underwent a
      standardized protocol for CP/CPPS including a history, physical examination,
      standard 4-glass test, plus urethral swab and semen for microscopy and culture,
      uroflowmetry and residual urine determination. Treatment followed a best evidence
      based strategy with a standardized monotherapy based algorithm. RESULTS: A total
      of 100 consecutive patients with CP/CPPS (average age 42.2 years, range 20 to 70
      and average symptom duration 6.5 years, range 0.5 to 39) had 1-year followup
      after initial evaluation. Patients were prescribed treatment based on
      documentation of "failed," "successful" and "never tried" therapies based on a
      standardized treatment algorithm. Patients treated successfully were continued on
      the prescribed therapy, while therapy was discontinued and new therapy instituted
      (based on algorithm) in those in whom the initially prescribed therapy failed. At
      1 year there was a statistically significant decrease in total NIH-CPSI (23.3 to
      19.5, p = 0.0004), pain (11.0 to 9.4, p = 0.03) and quality of life (7.7 to 6.1,
      p <0.001), but not voiding (4.6 to 4.0, p = 0.12). A perceptible 25% decrease in
      total NIH-CPSI symptom score was noted in 37% and the greatest improvement was in
      the quality of life domain (43% of patients had greater than 25% improvement in
      quality of life). Of the patients 35% had a significant decrease of greater than
      6 points in total NIH-CPSI. A clear, clinically significant improvement in total
      NIH-CPSI (greater than 50% decrease) was noted in 19%. CONCLUSIONS: Approximately
      a third of patients with treatment refractory CP/CPPS undergoing extensive
      evaluation and therapy based on a sequential monotherapy treatment strategy in a
      specialized prostatitis clinic had at least modest improvement in symptoms during
      1 year. This study confirms that a treatment strategy based on the sequential
      application of monotherapies for patients with a long history of severe CP/CPPS
      remains relatively poor.

PMID- 15247728
TI  - Acute caffeine effects on urine composition and calcium kidney stone risk in
      calcium stone formers.
AB  - PURPOSE: Caffeine increases urinary calcium (ca) excretion in nonstone formers.
      We designed a study to determine the effect of caffeine consumption on urinary
      composition in stone formers. MATERIALS AND METHODS: A total of 39 normocalcemic
      patients with calcium stones consumed caffeine (6 mg/kg lean body mass) after 14
      hours of fasting. Urinary composition was compared 2 hours before and 2 hours
      after caffeine consumption. Control subjects included 9 nonstone formers studied
      contemporaneously with patients plus data from 39 nonstone formers from previous
      studies matched to each patient by level of fasting calcium/creatinine (Cr),
      gender and age. RESULTS: Caffeine increased urinary Ca/Cr, magnesium/Cr,
      citrate/Cr and sodium/Cr but not oxalate/Cr in stone formers and controls. The
      Tiselius stone risk index for calcium oxalate precipitation increased from 2.4 to
      3.1 in stone formers and from 1.7 to 2.5 in nonstone formers. Of the 39 stone
      formers 32 had an increased Tiselius risk index after caffeine. Post-caffeine
      increases in Ca/Cr and Na/Cr were highly correlated. CONCLUSIONS: Caffeine
      consumption may modestly increase risk of calcium oxalate stone formation.

PMID- 15247729
TI  - Percutaneous renal stone extraction: in vitro study of retrieval devices.
AB  - PURPOSE: Traditionally, percutaneous stone extraction has relied on the use of 2
      prong and 3-prong graspers, which are prone to causing trauma to the urothelium.
      We evaluate the efficiency of stone removal with a novel tipless stone basket
      designed specifically for percutaneous procedures. MATERIALS AND METHODS: A 3, 5
      and 8 mm human calculus were placed in the calix of a percutaneous renal model. A
      26Fr Storz nephroscope (27093B, Storz Medical AG, Kreuzlingen, Switzerland) was
      inserted through a 30Fr Amplatz sheath into the model with camera input from a
      Storz telecam SL-NTSC feeding to a 20-inch Sony Triniton monitor (Sony Corp of
      America, New York, New York). Operators were randomized to start stone extraction
      with a Storz 3-prong grasper (27090RB) or a Cook 12Fr Perc-NCircle (38 cm) (Cook
      Urological, Inc., Indianapolis, Indiana). Subsequent testing alternated between
      the 2 devices until 10 extraction attempts were conducted with each device. Time
      to extraction of all 3 calculi and number of inadvertent withdrawals of the
      sheath were recorded. Three experienced operators tested each device. RESULTS:
      Stone extraction times were shorter with the Cook Perc-NCircle than the 3-prong
      grasper for all operators. Mean time for stone extraction was 25.3 +/- 11.2
      seconds for the Perc-NCircle compared to 35.1 +/- 18.5 seconds for the 3-prong
      grasper (p = 0.016). Loss of access by inadvertent removal of the Amplatz sheath
      occurred in 53% of the attempts with the 3-prong grasper compared to 7% of
      attempts with the Perc-NCircle. CONCLUSIONS: The Cook Perc-NCircle facilitates a
      more expeditious approach to percutaneous stone removal with less risk of sheath
      withdrawal.

PMID- 15247730
TI  - Comparison of nitinol tipless stone baskets in an in vitro caliceal model.
AB  - PURPOSE: Tipless stone baskets facilitate caliceal calculi extraction during
      flexible ureteroscopy. We evaluated the stone capture rate of 9 commercially
      available tipless stone baskets in an in vitro model using novice and expert
      operators. MATERIALS AND METHODS: The Microvasive Zerotip (2.4Fr, 3.0Fr), Cook N
      Circle (2.2Fr, 3.0Fr, 3.2Fr), Bard Dimension (3.0Fr, Sacred Heart Medical Halo
      (1.9Fr), Vantage (1.9Fr) and Circon-ACMI Sur-Catch-NT (3.0Fr) were tested by 3
      novice and 3 experienced basket operators. Each operator performed stone
      extraction of 2, 5 and 8 mm calculi (size determined by digital caliper with 3
      repetitions of each basket. The time to extraction of the calculus from a convex
      based test tube caliceal model was recorded. Statistical analysis was performed
      using repeated measures ANOVA and Fisher's pairwise comparisons. RESULTS: After a
      learning curve of 27 basket retrievals, there was no significant difference in
      stone capture times between novice (38 +/- 54 seconds) and expert operators (32
      +/- 49 seconds, p = 0.174). For total stone capture (all sizes) the Sacred Heart
      Halo resulted in the most rapid stone extraction (17 +/- 14 seconds) by novices
      and experts, while the Sur-Catch NT resulted in the slowest stone extraction (78
      +/- 90, seconds, p = 0.001). The Halo (14 +/- 9 seconds) and Vantage (19 +/- 12
      seconds) baskets were significantly faster for 2 mm calculi than the N-Circle (73
      +/- 60 seconds, p = 0.006), Sur-Catch (169 +/- 85 seconds, p = 0.0005) and
      Dimension (73 +/- 70 seconds, p = 0.017). The Zerotip functioned well for 2 mm
      calculi in the hands of expert operators (15 +/- 9 seconds) but not novice
      operators (94 +/- 95 seconds). The Sur-Catch NT was significantly slower for 2 mm
      calculi than the N-Circle (p = 0.01), Dimension (p =.03), Halo (p =.0005),
      Vantage (p =.001) and Zerotip (p =.002). For 5 mm calculi the Halo was superior
      (12 +/- 8 seconds), while the Zerotip were superior for 8 mm calculi (8 +/- 3
      seconds) compared to the N-Circle (23 +/- 28 seconds, p = 0.026), Halo (26 +/- 18
      seconds, p = 0.021) and Vantage (23 +/- 15 seconds, p = 0.006). CONCLUSIONS: The
      Sacred Heart Halo and Vantage baskets resulted in the most expeditious stone
      extraction, especially for 2 to 5 mm calculi while the Microvasive Zerotip was
      optimal for 8 mm calculi. The Sur-Catch NT had the slowest stone capture rate for
      all stone sizes. Caliceal models of stone basketing may be useful to train novice
      urology residents and nursing assistants.

PMID- 15247731
TI  - A prospective randomized comparison of type of nephrostomy drainage following
      percutaneous nephrostolithotomy: large bore versus small bore versus tubeless.
AB  - PURPOSE: We compared postoperative outcomes among tubeless, conventional large
      bore nephrostomy drainage and small bore nephrostomy drainage following
      percutaneous nephrostolithotomy (PCNL) in a prospective randomized fashion.
      MATERIALS AND METHODS: Between January and June 2001, 30 patients undergoing PCNL
      were randomized to receive conventional large bore (20Fr) nephrostomy drainage
      (group 1, 10 patients), small bore (9Fr) nephrostomy drainage (group 2, 10
      patients) or no nephrostomy drainage (group 3, 10 patients). Inclusion criteria
      included a single subcostal tract, uncomplicated procedure, normal preoperative
      renal function and complete stone clearance. Factors compared among the 3 groups
      were postoperative analgesia requirement, urinary extravasation, duration of
      hematuria, duration of urinary leak, decrease in hematocrit and hospital stay.
      RESULTS: The postoperative analgesic requirement was significantly higher in
      group 1 (217 mg) compared to groups 2 (140 mg, p <0.05) and 3 (87.5 mg, p
      <0.0001). Patients in group 3 had a significantly shorter duration (4.8 hours) of
      urinary leak through the percutaneous renal tract compared to patients in groups
      1 (21.4 hours, p <0.05) and 2 (13.2 hours, p <0.05). Hospital stay was
      significantly shorter in group 3 (3.4 days) compared to groups 1 (4.4 days, p
      <0.05) and 2 (4.3 days, p <0.05). All 3 groups were similar in terms of operative
      time, duration of hematuria and decrease in hematocrit. Postoperative ultrasound
      did not reveal significant urinary extravasation in any case. CONCLUSIONS:
      Tubeless PCNL is associated with the least postoperative pain, urinary leakage
      and hospital stay. Small bore nephrostomy drainage may be a reasonable option in
      patients in whom the incidence of stent dysuria is likely to be higher.

PMID- 15247732
TI  - Nifedipine versus tamsulosin for the management of lower ureteral stones.
AB  - PURPOSE: We evaluate and compare the effectiveness of 2 different medical
      therapies during watchful waiting in patients with lower ureteral stones.
      MATERIALS AND METHODS: A total of 86 patients with stones less than 1 cm located
      in the lower ureter (juxtavesical or intramural tract) were enrolled in the study
      and were randomly divided into 3 groups. Group 1 (30) and 2 (28) patients
      received daily oral treatment of 30 mg deflazacort, (maximum 10 days). In
      addition group 1 patients received 30 mg nifedipine slow-release (maximum 28
      days) and group 2 received 1 daily oral therapy of 0.4 mg tamsulosin (maximum 28
      days), Group 3 patients (28) were used as controls. Statistical analyses were
      performed using Student's test, ANOVA test, chi-square test and Fisher's exact
      test. RESULTS: The average stone size for groups 1 to 3 was 4.7, 5.42 and 5.35
      mm, respectively, which was not statistically significant. Expulsion was observed
      in 24 of 30 patients in group 1 (80%), 24 of 28 in group 2 (85%) and 12 of 28 in
      group 3 (43%). The difference in groups 1 and 2 with respect to group 3 was
      significant. Average expulsion time for groups 1 to 3 was 9.3, 7.7 and 12 days,
      respectively. A statistically significant difference was noted between groups 2
      and 3. Mean sodium diclofenac dosage per patient in groups 1 to 3 was 19.5, 26,
      and 105 mg, respectively. A statistical significant difference was observed
      between groups 1 and 2 with respect to group 3. CONCLUSIONS: Medical treatments
      with nifedipine and tamsulosin proved to be safe and effective as demonstrated by
      the increased stone expulsion rate and reduced need for analgesic therapy.
      Moreover medical therapy, particularly in regard to tamsulosin, reduced expulsion
      time.

PMID- 15247733
TI  - Prospective randomized comparison of 2 ureteral access sheaths during flexible
      retrograde ureteroscopy.
AB  - PURPOSE: While the use of ureteral access sheaths facilitates flexible
      ureteroscopy, buckling or kinking of the device may preclude its successful
      application. We evaluate the ability of 2 hydrophilic coated ureteral access
      sheaths to obtain and maintain access to the upper collecting system. MATERIALS
      AND METHODS: A total of 54 flexible ureteroscopy procedures were randomized to
      use of the 12/15Fr Applied Access Forte XE (Applied Medical, Rancho Santa
      Margarita, California) or the 12/14Fr Cook Flexor (Cook Urological, Spencer,
      Indiana) access sheaths. Device failure was defined as buckling of the sheath
      that prevented adequate placement, kinking of the sheath after removal of the
      obturator or difficulty in passing instruments through the sheath. The ease of
      placement, instrument passage and stone extraction was scored from poor (1) to
      excellent (4). Fisher's exact test and Mann-Whitney tests were used for
      statistical comparisons. RESULTS: No patient required ureteral balloon dilation.
      There was no significant difference between the groups in regard to preoperative
      stenting (34% and 31%, p = 1.00) or rigid ureteroscopy before sheath placement
      (32% and 25%, p = 0.751). The device failure rate was 44% for the Applied sheath
      and 0% for the Cook sheath (p <0.001). Failures with the Applied sheath included
      buckling (25%), kinking (25%) and difficulty passing instruments (13%). The Cook
      sheath was rated superior with regard to ease of placement (3.89 vs 3.00, p =
      0.001), ease of instrument passage (3.97 vs 3.29, p = 0.001) and ease of stone
      extraction (3.74 vs 3.00, p = 0.023). CONCLUSIONS: The performance of the Cook
      Flexor sheath was superior with regard to overall failure and ease of use.

PMID- 15247734
TI  - Botulinum toxin type A: a novel approach to the treatment of recurrent urethral
      strictures.

PMID- 15247735
TI  - Long-term experience with surgical and conservative treatment of penile fracture.
AB  - PURPOSE: Immediate surgical repair is widely accepted as the therapy of choice in
      penile fracture. As recent reports show, good results can also be achieved in
      some patients with conservative management. It is unclear which patients will
      truly benefit from an operation. We retrospectively compared the long-term
      outcomes of surgical and conservative treatment in patients with penile fracture.
      MATERIALS AND METHODS: In 22 years we treated 29 patients with penile fracture. A
      total of 12 patients were treated with immediate surgical repair and 17 patients
      were treated conservatively. Patient charts were reviewed and all patients had
      followup by interview with an additional clinical evaluation if the result was
      not completely satisfactory. Outcome was rated good, moderate or poor. RESULTS:
      Mean followup was 67 months. There was no statistical difference between patients
      in the surgery group and patients in the conservative group in regard to length
      of followup, age at presentation or length of hospital stay. In the surgery group
      and the conservative group 11 (92%) and 10 (59%) patients showed good outcome,
      respectively. Poor outcome was seen in 3 patients from the conservative group.
      CONCLUSIONS: Overall, immediate surgery yields excellent results and is superior
      to nonoperative treatment in the management of penile fracture. However,
      conservative therapy restricted to uncomplicated cases can lead to an equally
      good outcome.

PMID- 15247736
TI  - The morbidity of buccal mucosal graft harvest for urethroplasty and the effect of
      nonclosure of the graft harvest site on postoperative pain.
AB  - PURPOSE: We assess the medium and long-term morbidity of buccal mucosal graft
      (BMG) harvest for urethroplasty, and evaluate the effect of nonclosure of the
      graft harvest site on postoperative pain. MATERIALS AND METHODS: A questionnaire
      was mailed to 110 men who underwent BMG urethroplasty between January 1, 1997 and
      August 31, 2002. Demographic data and side effects of BMG harvest, including oral
      pain, sensation and intake, were assessed postoperatively. A prospective study
      was then performed to compare 20 unselected men whose BMG donor site was closed
      with a group of 20 men in whom it was left open using a 5-point analog pain score
      that was completed twice daily for the first 5 postoperative days. RESULTS: A
      total of 49 men with a median age of 49 years (range 23 to 73) returned
      questionnaires relating to 57 BMG harvests. Of the graft harvests 47 (83%) were
      associated with postoperative pain, which was worse than expected in 24 (51%). Of
      the 57 patients 51 (90%) resumed oral liquid intake within 24 hours and 44 (77%)
      resumed normal diet within 1 week. Postoperative side effects included perioral
      numbness in 39 (68%) patients with 15 (26%) having residual numbness after 6
      months, initial difficulty with mouth opening in 38 (67%) with 5 (9%) having
      persistent problems, changes in salivation in 6 (11%) and mucous retention cyst
      that required excision in 1 (2%). The men in the prospective donor site study had
      a median age of 51 years (range 24 to 70). Mean pain score for patients with
      donor site closure was 3.68 and was significantly higher than that for patients
      without donor site closure (2.26, p < 0.01). CONCLUSIONS: Buccal mucosal graft
      harvest is not a pain-free procedure. Closure of the harvest donor site appears
      to worsen this pain and it may be best to leave harvest sites open. The main long
      term complications are perioral numbness, persistent difficulty with mouth
      opening and change in salivary function.

PMID- 15247737
TI  - The orthotopic T pouch ileal neobladder: experience with 209 patients.
AB  - PURPOSE: A serous lined extramural ileal flap valve technique called the T limb
      was developed to prevent reflux of urine in an orthotopic bladder substitute
      called the T pouch. We evaluate our intermediate clinical and functional
      experience with the orthotopic T pouch ileal neobladder. MATERIALS AND METHODS:
      From November 1996 through May 2000, 209 patients (169 men [80%], 40 women), with
      a mean age of 69 years (range 33 to 93) underwent construction of an orthotopic T
      pouch ileal neobladder after cystectomy. The indication for cystectomy included
      bladder cancer in 198 patients (95%). Median followup for the entire cohort was
      33 months (range 0 to 69). Data were analyzed according to perioperative
      mortality, early (within 3 months) and late diversion related and diversion
      unrelated complications, radiographic evaluation of the upper urinary tract and
      urinary reservoir, and determination of renal function. RESULTS: Three patients
      (1.4%) died perioperatively. A total of 63 (30%) early complications occurred, 53
      (25%) diversion unrelated and 10 (5%) diversion related. The most common early
      diversion unrelated complication was dehydration (10 patients). The most common
      early diversion related complication was urine leak in 6 patients. There were no
      early complications directly related to the antirefluxing T limb. Late
      complications occurred in 68 (32%) patients including 30 (14%) diversion
      unrelated and 38 (18%) diversion related. The most common late diversion
      unrelated complication was incisional hernia in 16 patients. Of the 38 late
      diversion related complications the most common were pouch calculi in 17 and
      ureteroileal obstruction in 9 patients. The only late complication directly
      related to the T limb was stenosis in 4 patients, 3 of whom received adjuvant
      pelvic radiation. A total of 181 patients had radiographic evaluation of the
      upper urinary tract including 162 (90%) with a normal radiographic study or
      evidence of postoperative decompression. An abnormal upper tract study was seen
      in 18 patients (10%) including 9 with ureteroileal obstruction and 4 with
      afferent T limb stenosis. Gravity cystography of the neobladder was normal in 143
      of 158 (90%) evaluable patients. Reflux was seen in 15 patients (10%). Renal
      function as determined by serum creatinine was stable or improved in 96% of
      patients. Good daytime and nighttime continence was reported in 87% and 72% of
      evaluable patients, respectively. Overall 75% of patients complete void while 25%
      required some form of intermittent catheterization to empty the neobladder
      completely including 20% of men and 43% of women. CONCLUSIONS: With intermediate
      followup the functional results of the T pouch ileal neobladder are acceptable.
      The antirefluxing T limb provides unobstructed urinary flow in 95% and reflux
      prevention in 90% of patients. Although these results are encouraging, further
      followup is required to assess the long-term results of the T pouch ileal
      neobladder.

PMID- 15247738
TI  - Continent cutaneous ileal pouch using the serous lined extramural valves. The
      Mansoura experience in more than 100 patients.
AB  - PURPOSE: We report on the functional results of continent ileal reservoir using
      serous lined extramural valves for reflux prevention and continent urinary
      outlet. MATERIALS AND METHODS: The procedure was performed in 109 patients (68
      men, 27 women and 14 children). The operation was indicated as a primary
      procedure in 93 patients and for conversion in 16. The technique entailed
      construction of a detubularized W-shaped ileal reservoir in which 2 serous lined
      troughs were created. Two tapered ileal segments were used, 1 for reflux
      prevention and the other as a continent outlet. The appendix was used for the
      construction of the outlet in 44 patients. RESULTS: Two patients died in the
      hospital of pulmonary embolism. A total of 22 early complications were observed
      in 18 patients (16.5%). None of the patients required operative intervention. A
      total of 93 patients were evaluable with a mean followup of 36.6 +/- 25.4 months.
      All evaluable patients but 5 were continent day and night. Mean time for
      catheterization was 4 to 5 hours. There were 14 late complications reported in 11
      patients (11.8%), including pouch stones in 5, stomal stenosis in 5, failure to
      catheterize in 2, parastomal hernia in 1 and adhesive bowel obstruction in 1.
      Upper urinary tract was stable or improved in 94.8% of the renal units. Clinical
      acidosis did not develop in any of the patients. CONCLUSIONS: Serous lined
      unidirectional valves are reliable. They provide a versatile surgical technique
      suitable for urinary diversion or conversion procedures. The operation is
      associated with an acceptable complication rate and is followed by good
      functional results.

PMID- 15247739
TI  - 15-year experience with the management of extrinsic ureteral obstruction with
      indwelling ureteral stents.
AB  - PURPOSE: We assessed the success of retrograde placement of indwelling ureteral
      stents in the management of ureteral obstruction due to extrinsic compression.
      MATERIALS AND METHODS: Between July 1987 and December 2002 adequate followup was
      available for 101 patients who underwent primary retrograde ureteral stenting for
      extrinsic ureteral obstruction. Mean age at presentation was 61.4 years (range 33
      to 90). Chart review was performed on all patients for primary diagnosis,
      symptomatology, degree of hydronephrosis, creatinine levels (baseline, treatment
      and posttreatment), location of compression, size and number of stents used,
      progression to percutaneous nephrostomy tube (PNT), stent failure, days to stent
      failure, post-stent therapy and status at last followup. RESULTS: Mean length of
      followup was 11 months (range 1 to 127). In 101 patients 138 ureteral units (UU)
      were stented. Total stent failure occurred in 41 (40.6%) patients and 58 (42.0%)
      UU. A total of 40 (29.0%) UU required PNTs at a mean of 40.3 days (range 0 to
      330) with 18 PNTs placed in less than 1 week. Cases of stent failure that did not
      undergo PNT placement included 18 (13.0%) UU at a mean of 52.4 days (range 3 to
      128). A total of 90 (89.1%) patients had metastatic cancer at stenting with 32.2%
      dead at 5.8 months (range 1 to 32). Univariate and multivariate analyses
      identified cancer diagnosis, baseline creatinine greater than 1.3 mg/dl and post
      stent systemic treatment as predictors of stent failure. Proximal location of
      compression and treatment creatinine greater than 3.11 mg/dl were marginal
      predictors of failure on univariate analysis, while proximal location of
      obstruction was also marginally significant on multivariate analysis. No
      predictors were identified for early stent failure (less than 1 week).
      CONCLUSIONS: At almost 1 year followup stent failure due to extrinsic compression
      occurred in nearly half of treated patients. Analysis of data revealed a
      diagnosis of cancer, baseline mild renal insufficiency and metastatic disease
      requiring chemotherapy or radiation as predictors of stent failure. Managing
      extrinsic compression by retrograde stenting continues to be a practical but
      guarded decision and should be tailored to each patient.

PMID- 15247741
TI  - Does concomitant stress incontinence alter the efficacy of tolterodine in
      patients with overactive bladder?
AB  - PURPOSE: Muscarinic antagonists such as tolterodine are the treatment of choice
      for overactive bladder (OAB). We determined the impact of concomitant stress
      incontinence (SI) on the therapeutic effects of tolterodine in patients with OAB
      with and without concomitant SI. MATERIALS AND METHODS: Data from an open label,
      observational study involving 2,250 patients with OAB symptoms were analyzed for
      baseline frequency, urgency and incontinence, and alterations in these symptoms
      while on 12-week treatment with 2 mg tolterodine twice daily. Data are shown as
      the mean +/- SD. The statistical significance of differences in treatment effects
      was determined by multiple regression analysis, adjusting for gender, age and
      baseline symptom intensity. RESULTS: Concomitant I to III degree SI according to
      the Stamey grading was present in 31%, 15% and 2% of patients, respectively, and
      it was associated with increasing basal incontinence, although only III degree SI
      was associated with greater baseline frequency or urgency. In the overall group
      tolterodine decreased frequency, urgency and urge incontinence from 12.4 +/- 4.3
      to 7.7 +/- 2.7, 8.4 +/- 5.1 to 2.0 +/- 3.0 and 3.4 +/- 4.2 to 0.8 +/- 2.0
      episodes daily, respectively. On multiple linear regression analysis I and II
      degree SI had a minor, if any, effect on this improvement, while III degree SI
      was statistically associated with a smaller decrease in frequency (by 1.4 +/- 0.4
      micturitions daily, p = 0.0002) and incontinence (by 2.1 +/- 0.3 episodes daily,
      p < 0.0001) but with similar alterations in the number of urge episodes.
      CONCLUSIONS: Concomitant I or II degree SI has little effect on the efficacy of
      tolterodine in OAB cases. Only patients with concomitant III degree SI have
      significantly less improvement.

PMID- 15247740
TI  - Role of C afferent fibers and monitoring of intravesical resiniferatoxin therapy
      for patients with idiopathic detrusor overactivity.
AB  - PURPOSE: Resiniferatoxin (RTX) is a specific C fiber neurotoxin which produces
      desensitization. In this study we performed intravesical RTX therapy in patients
      with idiopathic detrusor overactivity. In addition we measured the current
      perception threshold of C and A delta fibers before and after treatment to
      evaluate clinical significance. MATERIALS AND METHODS: The protocol involved an
      RTX solution (100 ml of 50 nM) instilled in the bladder for 30 minutes. Four men
      and 6 women 59 to 75 years old were treated. Effects on bladder function were
      evaluated before and 30 days after treatment by cystometry and Neurometer
      (Neurotron, Inc., Baltimore, Maryland). Subjective and objective measures
      included bladder diaries and quality of life before treatment, and 7, 30 and 90
      days subsequently. RESULTS: Of the 10 patients 5 noted improvement and 2 of them
      became dry. The other 5 patients were considered to have stationary symptoms.
      Mean maximal cystometric capacity +/- SD increased from 229 +/- 108 ml at
      baseline to 271 +/- 99.5 ml at 30 days (p = 0.04). The mean number of daily
      episodes of urinary incontinence decreased from 3.5 +/- 2.2 to 2.0 +/- 1.6 (p =
      0.008) at 7 days, to 1.9 +/- 1.6 (p = 0.018) at 30 days and to 2.5 +/- 1.7 (p =
      0.018) at 90 days. Mean current perception threshold values of C and A delta
      fibers did not change significantly, from 46.9 +/- 35.2 to 56.4 +/- 32.1 (p =
      0.161) and from 66.9 +/- 31.7 to 66.4 +/- 25.2 (p = 0.952), respectively.
      However, values of C fibers increased in all patients who showed improvement from
      46.2 +/- 33.2 to 64.0 +/- 36.8 (p = 0.043). CONCLUSIONS: Intravesical RTX
      improved bladder capacity and leak episodes in patients with idiopathic detrusor
      overactivity. Intravesical RTX is a promising treatment for this condition.

PMID- 15247742
TI  - Urethral stent for the treatment of detrusor-sphincter dyssynergia: evaluation of
      the clinical, urodynamic, endoscopic and radiological efficacy after more than 1
      year.
AB  - PURPOSE: We studied the intermediate-term clinical, urodynamic, endoscopic and
      radiological efficacy of the Ultraflex urethral stent (Boston Scientific Co.,
      Boston, Massachusetts) for the treatment of detrusor-sphincter dyssynergia (DSD)
      in spinal cord injured patients. MATERIALS AND METHODS: A total of 47 consecutive
      men presenting with DSD due to spinal cord injury (39) or various spinal cord
      diseases (9) were treated with the Ultraflex stent. DSD was demonstrated by
      urodynamic assessment with electromyographic recording of the striated urethral
      sphincter muscle activity. RESULTS: Postoperatively, all patients voided by
      reflex. The number of patients with symptomatic postoperative urinary tract
      infection decreased significantly (p <0.001). Urodynamic assessment (mean
      followup +/- SD 2.2 +/- 1.3 years) showed reduction of mean peak detrusor
      pressure from 65.7 +/- 27.8 to 46.4 +/- 28.8 cm H2O (p <0.005) and reduction of
      mean residual urine from 231.6 +/- 168.1 to 70.3 +/- 85.6 ml (p <0.0005). Mean
      urethral closing pressure was markedly reduced from 73.9 +/- 40.9 to 23.8 +/-
      25.1 cm H2O (p <0.0005). Mean endoscopic followup was 1.7 +/- 1.1 years. Mean
      percentage of epithelialization was 90.8% +/- 19.7%, and no obstructive
      granulation tissue or stone encrustation was observed inside the stent. On
      ultrasound signs of hydronephrosis persisted in only 1 of 8 patients. There were
      no immediate postoperative complications. Complementary bladder neck incision was
      performed in 21% of patients. CONCLUSIONS: The Ultraflex stent appears to be
      effective for intermediate-term treatment of DSD on the basis of clinical,
      urodynamic, endoscopic and radiological parameters.

PMID- 15247743
TI  - The male perineal sling: comparison of sling materials.
AB  - PURPOSE: Urinary incontinence continues to be a significant problem for patients
      after radical prostatectomy. The male perineal sling is emerging as a safe and
      effective treatment option for postprostatectomy stress urinary incontinence. We
      compare the efficacy of porcine dermal collagen and silicone mesh as the sling
      material. MATERIALS AND METHODS: Of 36 patients with postprostatectomy stress
      urinary incontinence a porcine dermal collagen sling was placed in 20 and a
      silicone mesh sling was placed in 16. The sling was placed at the bulbar urethra
      and secured to 3 titanium bone screws anchored into the medial aspect of
      bilateral inferior pubic rami. RESULTS: Results at 12 months were compared. In
      the dermis group 9 (56%) patients were cured of incontinence (no pads daily), 5
      (31%) had significant improvement (decrease of 50% or more in pads daily) and 2
      (13%) had no change in symptoms. In the silicone mesh group 14 (87%) patients
      were cured of incontinence and 2 (13%) were significantly improved. Results
      showed that a previously placed artificial urinary sphincter led to poorer
      outcomes but a history of radiation therapy did not affect results. The most
      common complication was temporary urinary retention observed in 1 (5%) patient in
      the dermis group and 2 (12%) in the silicone mesh group. CONCLUSIONS: Early
      results demonstrate that the male sling is a safe and efficacious treatment
      option for postprostatectomy urinary incontinence. This study demonstrates
      superior outcomes with the synthetic silicone mesh sling compared to the porcine
      dermal collagen.

PMID- 15247744
TI  - Safety and efficacy of transurethral resection of prostate glands up to 150 ml: a
      prospective comparative study with 1 year of followup.
AB  - PURPOSE: We investigated the safety and efficacy of transurethral resection of
      the prostate (TURP) for prostate glands between 70 and 150 ml. MATERIALS AND
      METHODS: We prospectively evaluated 113 patients treated with TURP for benign
      prostatic hyperplasia. A total of 57 patients with a prostate volume of less than
      70 ml were assigned to group 1, while 56 with a prostate volume of between 70 and
      150 ml were assigned to group 2. Preoperative parameters considered in each
      patient were prostate volume, International Prostate Symptom Score (I-PSS),
      urinary flow rate measurement (Qmax) and post-void residual urine volume (PVR).
      Operative time, resected tissue weight and all complications were recorded. All
      patients were evaluated 3 months and 1 year postoperatively. Preoperative,
      perioperative and postoperative data on the 2 groups were compared. RESULTS: Each
      group achieved significant improvement in I-PSS, Qmax and PVR. Operative time was
      significantly longer in group 2 but the complication rate was similar in the 2
      groups. Group 2 resulted in better improvements in Qmax and I-PSS. At 1 year of
      followup PVR was significantly lower in group 1 than in group 2. Multivariate
      analysis revealed that only age was a significant independent predictor of
      complications, and only age and initial Qmax were independent predictive
      variables of outcome. CONCLUSIONS: TURP for large prostate glands is a safe
      procedure without showing a different complication rate compared with TURP for
      recommended volumes. Patients with a baseline prostate volume of greater than 70
      ml seem to achieve better improvement in obstruction and symptoms.

PMID- 15247745
TI  - Holmium laser resection of the prostate versus transurethral resection of the
      prostate: results of a randomized trial with 4-year minimum long-term followup.
AB  - PURPOSE: It has previously been shown that holmium laser resection of the
      prostate (HoLRP) is superior to transurethral resection of the prostate (TURP)
      with regard to perioperative morbidity and is equivalent to TURP in the short
      term. We present the long-term results of a randomized, prospective trial
      comparing HoLRP to TURP since information regarding the durability of holmium
      prostatectomy is lacking in the literature to date. MATERIALS AND METHODS: A
      total of 120 patients with urodynamic obstruction were randomized (April 1996 to
      August 1997) into 2 comparable groups and assigned to HoLRP or TURP. All patients
      were assessed preoperatively and followed prospectively at 3 weeks, 3, 6, 12, 24
      and 48 months postoperatively with an American Urological Association symptom
      score, quality of life score, peak urinary flow rate, and questionnaires
      concerning sexual function and continence. Preoperative pressure flow studies,
      ultrasound prostatic volume assessment and post-void residual volume measurement
      were repeated at the 6-month visit. All adverse events were noted. RESULTS: Of
      120 patients 73 completed the 48-month assessment. HoLRP and TURP resulted in
      significant improvements in all parameters. There was no difference between the 2
      techniques in terms of urodynamic parameters, potency, continence and symptom
      scores at the 48-month assessment. HoLRP took significantly longer to perform but
      perioperative morbidity, catheter time, nursing contact time and hospital stay
      were significantly less for HoLRP compared to TURP. CONCLUSIONS: HoLRP and TURP
      give equivalent and satisfactory long-term results, with no differences noted in
      major morbidity. This confirms the durability of these 2 treatments. Peri
      operative morbidity is less with HoLRP.

PMID- 15247746
TI  - Self-expanding polytetrafluoroethylene covered nitinol stents for the treatment
      of ureteral stenosis: preliminary report.
AB  - PURPOSE: We evaluated the treatment of ureteral stenosis using a self-expanding
      nitinol stent covered with expanded polytetrafluoroethylene (ePTFE). MATERIALS
      AND METHODS: Between January 2001 and April 2003, 37 ePTFE covered metal stents
      were implanted in 20 patients with a total of 29 ureteral stenoses due to various
      causes. In general the stents were introduced by using a retrograde approach
      under combined endoscopic and fluoroscopic guidance with patients under spinal
      block and sedation. Followup assessments in 18 patients, including urography,
      were done 3, 6, 12, 18 and 24 months after the procedure. Followup endoscopic
      examinations were performed at 6 and 12 months in 8 patients. RESULTS: Immediate
      ureteral patency was achieved during all insertion procedures and maintained in
      most patients. Four patients died of the neoplastic process 3 to 12 months after
      implantation. Four stent migrations occurred in 3 patients (22.2%), which was
      resolved by implanting a new stent. Nonobstructive mucous hyperplasia was
      observed in 5 patients (27.7%) at the end of the stent, although there was no
      internal calcification. In all cases the stents remained patent until the current
      time or until patient death. CONCLUSIONS: We found that ePTFE covered nitinol
      stents were safe and effective for ureteral stenosis. Their resistance to
      calcification was high with nonobstructive hyperplasia developing in only a few
      cases and only at the stent ends. The ideal material for covering stents would
      produce no mucous hyperplasia.

PMID- 15247747
TI  - Is there a clinical relevance of partial androgen deficiency of the aging male?
AB  - PURPOSE: Aging in men is characterized by a progressive, generally moderate
      decrease in plasma testosterone (T) levels and T substitution is increasingly
      prescribed. However, the association of partial androgen deficiency of the aging
      male with clinical symptoms and the ideal screening test are controversial. We
      investigate the association between various T measures and clinical and
      biochemical parameters of the aging male. MATERIALS AND METHODS: We investigated
      the association between total (TT), calculated free (FTcalc) and bioavailable
      (BT) testosterone, and various clinical and biochemical parameters in 51 healthy
      community living male volunteers, 55 and 75 years old. The parameters included
      serum levels of sex hormone-binding globulin, estradiol and lipid profile after
      an overnight fast; questionnaires assessing clinical symptoms, erectile function
      and mood; bone mineral density and body composition. RESULTS: TT correlated with
      FTcalc (r2 = 0.71, p <0.001) but not with BT (r2 = 0.04, p not significant) and
      FTcalc correlated moderately with BT (r2 = 0.23, p <0.001). Testicular volume
      correlated with TT levels (r2 = 0.17, p <0.001) and FTcalc (r2 = 0.17, p <0.001)
      but not with BT. There was neither a correlation of TT, FTcalc nor BT values with
      clinical symptoms nor with biochemical and radiological parameters, ie affective
      symptoms and sexual interest, circulating estradiol, lipid levels, bone mineral
      density or lean body mass. CONCLUSIONS: T values in our study sample did not
      correlate with clinical signs and symptoms of hypogonadism. Thus, according to
      our data, symptoms of the aging male could be rather multifactorial and should
      not be indiscriminately assigned to the age associated decrease in T levels.

PMID- 15247748
TI  - Ionic currents in single smooth muscle cells of the human vas deferens.
AB  - PURPOSE: Smooth muscle cells of the vas deferens have an important role in
      carrying sperms to the exterior but little is known of their electrophysiological
      properties. We characterized the voltage-gated ion channel currents in single
      smooth muscle cells of the human vas deferens (HVSMCs). MATERIALS AND METHODS: We
      observed contractile responses of 8 circular smooth muscle strips of the human
      vas deferens to a high concentration (10 mM) of tetraethylammonium. HVSMCs were
      isolated using proteolytic enzymes (collagenase and papain), and were used for an
      electro-physiological study using whole cell and inside-out patch clamp
      configurations. RESULTS: The application of 10 mM tetraethylammonium induced
      rhythmic contractions of the strips. When HVSMCs were dialyzed with a KCl
      solution, step depolarizations of membrane potential evoked oscillatory outward K
      currents that were not inactivated. The large conductance Ca activated K (BKCa)
      and delayed rectifier components of the outward current were identified. The BKCa
      channel showed a large single channel conductance (162.7 +/- 13.2 pS with 5 mM K
      in the patch pipette). Two types of Ca currents were identified in the whole cell
      configuration. With a cell held at -50 mV an L-type Ca current was present during
      a depolarizing step pulse. From a holding potential of -90mV L-type and T-type Ca
      currents were elicited by depolarizing step pulses. CONCLUSIONS: HVSMCs have 2 (L
      and T) types of Ca channels and 2 types of K (BKCa and delayed rectifier)
      channels. Voltage dependent changes of these ion channels and their interactions
      may be important in regulating vas contractility.

PMID- 15247749
TI  - Intravasal "toothpaste" in men with obstructive azoospermia is derived from vasal
      epithelium, not sperm.
AB  - PURPOSE: Men undergoing vasectomy reversal many years after vasectomy are at
      increased risk for secondary epididymal obstruction. When this occurs the
      intravasal fluid is often a thick, white, toothpaste-like material devoid of
      sperm. In this study we characterize the vasal fluid found in men with a newly
      described entity, segmental dysplasia of the vas deferens, in which at least 2
      distinct sites of vasal obstruction are present. We determine the significance of
      this fluid in men with obstructive azoospermia. MATERIALS AND METHODS: Three men
      who underwent scrotal exploration for obstructive azoospermia due to segmental
      dysplasia of the vas deferens were evaluated. Each underwent scrotal exploration
      including bilateral vasotomy and testicular biopsy. Intravasal fluid was
      collected, evaluated microscopically and sent for cytopathological evaluation.
      RESULTS: All men had isolated segments of the vas 2 to 5 cm in length that were
      not connected to the epididymis or ejaculatory ducts. We have named this
      condition segmental dysplasia of the vas deferens. Vasotomy was performed between
      aplastic segments, revealing thick, white, toothpaste-like material identical to
      that seen in men with secondary epididymal obstruction undergoing vasectomy
      reversal. Cytopathological evaluation of this fluid revealed proteinaceous
      concretions and rare clusters of degenerated columnar epithelial cells, but no
      sperm or sperm products. CONCLUSIONS: Thick, white, toothpaste-like material is
      produced between 2 obstructed segments as seen in men with segmental dysplasia of
      the vas deferens and with secondary epididymal obstruction. Our findings in men
      with segmental dysplasia of the vas deferens indicate that vasal "toothpaste"
      must be derived from vasal epithelium, not sperm.

PMID- 15247750
TI  - Erectile dysfunction after a long-distance cycling event: associations with
      bicycle characteristics.
AB  - PURPOSE: We conducted a prospective cohort study to examine the relationship
      between bicycle characteristics and the occurrence of erectile dysfunction.
      MATERIALS AND METHODS: Subjects consisted of 463 cyclists completing a cycling
      event of at least 320 km who were free of erectile dysfunction before their
      event. RESULTS: The cumulative incidence of erectile dysfunction after the ride
      was 4.2% (95% confidence interval [CI] 2.4%-6.8%) and 1.8% (95% CI 0.7%-3.8%) 1
      week and 1 month after the event, respectively. Bicycle characteristics
      associated with an increased risk of erectile dysfunction included a mountain
      bicycle compared with a road bicycle (risk ratio [RR] 4.1, 95% CI 1.6-12.5), and
      the relative height of the handlebars parallel with or higher than the saddle
      compared with the relative handlebar height lower than the saddle (RR 3.0, 95% CI
      1.1-9.3). Perineal numbness during the ride was experienced by 31% of the
      cyclists and was associated with erectile dysfunction (RR 4.4, 95% CI 1.6-12.7).
      Saddle cutouts were associated with an increased risk of erectile dysfunction
      among those who experienced numbness (RR 6.0, 95% CI 1.3-27.1), but the
      association was reversed among those who did not report numbness (RR 0.3, 95% CI
      0.0-2.5). CONCLUSIONS: If the associations described are causal, then cyclists on
      a long-distance ride may be able to decrease the risk of erectile dysfunction by
      riding a road bicycle instead of a mountain bicycle, keeping handlebar height
      lower than saddle height and using a saddle without a cutout if perineal numbness
      is experienced.

PMID- 15247751
TI  - Fibrous hamartoma of corpus cavernosum: a rare cause of congenital penile
      curvature associated with erectile dysfunction.

PMID- 15247752
TI  - Sexual function after highly selective embolization of cavernous artery in
      patients with high flow priapism: long-term followup.
AB  - PURPOSE: We present 15 cases of high flow priapism treated by selective
      embolization and evaluate erectile function at long-term followup. MATERIALS AND
      METHODS: Between 1995 and 2001, 15 patients underwent highly selective
      embolization of the cavernous artery for high flow priapism. Trauma was reported
      by 12 of the 15 patients, and no etiologic causes were evident in the other 3.
      The fistula was unilateral in 13 patients and bilateral in 2. All patients
      underwent embolization during arteriography. Erectile function was determined
      using the International Index of Erectile Function (IIEF) at followup after an
      average of 55 months (range 18 to 93). RESULTS: Postoperative color Doppler
      ultrasonography showed no recurrence in 11 patients (73%). Repeat pelvic
      angiography with selective embolization was required at 1 month postoperatively
      in 3 patients (20%). In 1 case (7%) 3 consecutive embolizations were not
      conclusive and a surgical operation was required. The IIEF results showed that
      sexual function was in the normal range in 80% of patients. Three patients (20%)
      reported a slight change in the quality of erection. Mean postoperative IIEF
      score was 26.3 (range 18 to 30). CONCLUSIONS: Highly selective embolization of
      the fistula is an effective and safe treatment option for high flow priapism
      because it ensures a high level of preservation of pretreatment erectile
      function.

PMID- 15247753
TI  - Sexual function and satisfaction in men after laser treatment for penile
      carcinoma.
AB  - PURPOSE: We evaluate sexual function, sexual satisfaction and cosmetic results
      after laser treatment of penile carcinoma. MATERIALS AND METHODS: A total of 67
      patients were treated at our clinic for penile cancer using combined carbon
      dioxide and neodymium:YAG lasers from 1986 to 2000. At the time of this study 58
      men, with a mean age of 64 years were alive, of whom 46 (79%) agreed to
      participate in a structured face-to-face interview addressing sexual function,
      sexual satisfaction and cosmetic results. The length of time that had elapsed
      since treatment ranged from 6 months to 15 years (median 3 years). RESULTS: Of 40
      patients (87%) who had been sexually active before treatment 30 (75%) had resumed
      activities at the time of the interview. Unaltered erectile function after
      treatment was reported by 33 patients (72%), 10 patients (22%) reported decreased
      function and 3 (6%) reported improved function. Of the 46 patients 23 (50%) were
      satisfied/very satisfied with their sexual life. After treatment only 3 of 30
      (10%) of the evaluable men had dyspareunia. The cosmetic results were considered
      satisfying/very satisfying by 36 (78%) men. CONCLUSIONS: Laser treatment of
      localized penile carcinoma preserves the penis and generally provides
      satisfactory sexual function and cosmetic results.

PMID- 15247754
TI  - The efficacy and safety of tadalafil in United States and Puerto Rican men with
      erectile dysfunction.
AB  - PURPOSE: We evaluate the efficacy and safety of tadalafil, taken as needed, in
      men with mild to severe erectile dysfunction (ED) and assess sexual intercourse
      attempt patterns. MATERIALS AND METHODS: In this multicenter, double-blind,
      placebo controlled, parallel study conducted in the United States and Puerto Rico
      207 men with ED were randomized to placebo or 20 mg tadalafil for 12 weeks. The
      primary efficacy variables were changes from baseline in the mean International
      Index of Erectile Function erectile function domain score and mean per patient
      percentage of "yes" responses to Sexual Encounter Profile (SEP) diary questions 2
      (successful penetration) and 3 (successful intercourse). The Global Assessment
      Question was a secondary end point and post hoc analyses on sexual intercourse
      attempt patterns were conducted. RESULTS: Men treated with tadalafil compared
      with placebo reported greater mean changes from baseline on the erectile function
      domain score (9.3 vs 0.3 with placebo, p <0.001) and on the mean per patient
      percentage of successful penetration (SEP question 2, 31.6% vs 2.3% with placebo,
      p <0.001) and successful intercourse attempts (SEP question 3, 43.6% vs 3.5% with
      placebo, p <0.001). The per treatment group percentage of successful intercourse
      attempts during treatment was higher for tadalafil than placebo (67.6% vs 24.1%,
      respectively, p <0.001) and most successful intercourse attempts occurred between
      4 and 36 hours after taking tadalafil. Of the men treated with tadalafil 82.8%
      reported improved erections versus 19.6% taking placebo (Global Assessment
      Question, p <0.001). The most common treatment emergent adverse events were
      headache (15.7% vs 6.3% with placebo), back pain (8.8% vs 0%), and dyspepsia
      (7.5% vs 0%). CONCLUSIONS: Tadalafil (20 mg) significantly improved erectile
      function and patients did not closely temporally link sexual intercourse attempts
      with taking tadalafil. Tadalafil was also well tolerated in both groups of men
      with mild to severe ED.

PMID- 15247755
TI  - Randomized study of testosterone gel as adjunctive therapy to sildenafil in
      hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.
AB  - PURPOSE: We compare the efficacy of testosterone gel (T-gel) versus placebo as
      adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who
      do not respond to sildenafil alone. MATERIALS AND METHODS: A randomized, placebo
      controlled, double-blind, parallel group, multicenter study was performed. A
      total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone
      400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were
      randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as
      adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were
      evaluated for sexual function, primarily based on the International Index of
      Erectile Function (IIEF), quality of life and serum testosterone levels at
      baseline and weeks 4, 8 and 12. RESULTS: Testosterone treated subjects had
      greater improvement in erectile function compared to those who received placebo,
      reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3,
      4.7). Similar trends were observed for improvements in orgasmic function, overall
      satisfaction, total IIEF score and percentage of IIEF responders. T-gel
      significantly (p < or =0.004) increased total and free testosterone levels
      throughout the study, although no significant correlations were made between
      testosterone levels and the IIEF at end point. CONCLUSIONS: T-gel taken with
      sildenafil may be beneficial in improving erectile function in hypogonadal men
      with erectile dysfunction who are unresponsive to sildenafil alone.

PMID- 15247756
TI  - Fate of the retained reservoir after replacement of 3-piece penile prosthesis.
AB  - PURPOSE: We evaluated patients who underwent surgery for implant malfunction to
      determine whether retaining the reservoir was associated with an increased risk
      of erosion or infection. We also reviewed the literature to study possible risk
      factors for reservoir erosion. MATERIALS AND METHODS: We reviewed the records of
      85 patients who underwent 98 procedures for replacement of a malfunctioning 3
      piece penile implant. Of these patients 13 underwent 2 replacement procedures. At
      the time of primary surgery the reservoir was placed in either the retropubic
      space or extraperitoneally in the lower lateral abdomen if the patient had
      undergone prior pelvic surgery. During surgery for replacement of the
      malfunctioning implant the cylinders and pump were removed, and the reservoir of
      the original 3-piece device was retained. During followup patients were assessed
      for implant function and the development of any complication such as infection
      and/or reservoir erosion into the bladder or bowel. RESULTS: Infection developed
      in 1 patient and implant malfunction occurred in 13 but no patient had erosion of
      the retained reservoir. All 85 patients had a functioning implant at a mean
      followup of 50 months (range 12 to 148). Review of the literature suggests that
      prior pelvic surgery and infection are major risk factors for reservoir erosion.
      CONCLUSIONS: Retaining the reservoir during replacement of malfunctioning 3-piece
      implants is not associated with a significant risk of erosion and routine removal
      is not necessary. Prior pelvic surgery and infection appear to be risk factors
      for reservoir erosion.

PMID- 15247757
TI  - Virtual ureteroscopy predicts ureteroscopic proficiency of medical students on a
      cadaver.
AB  - PURPOSE: Training on a virtual reality (VR) simulator has been shown to improve
      the performance of VR endoscopic tasks by novice endoscopists. However, to our
      knowledge the translation of VR skills into clinical endoscopic proficiency has
      not been demonstrated. We established criterion validity for a VR ureteroscopy
      simulator by evaluating VR trained subjects in a cadaver model. MATERIALS AND
      METHODS: A total of 32 participants, including 16 medical students and 16 urology
      residents, were evaluated at baseline on a VR ureteroscopy simulator (Uromentor,
      Simbionix, Lod, Israel), performing simple diagnostic ureteroscopy. The students
      then underwent 5 hours of supervised training on the simulator. Two weeks later
      all participants were reevaluated (VR2) on the simulator when repeating the
      initial task. Each participant was then assessed on the performance of a similar
      diagnostic ureteroscopy in a male cadaver. RESULTS: In medical students VR2 and
      cadaver performances correlated closely for several measured parameters (total
      time for task completion and overall global ratings score). In contrast, there
      was little correlation between the 2 performances in residents. Indeed,
      performance on the cadaver correlated more closely with the training level than
      VR2 scores. Despite VR training medical students were unable to perform cadaver
      ureteroscopy comparably to residents. CONCLUSIONS: For novice endoscopists
      performance on the simulator after training predicted operative (cadaver)
      performance and, thus, it may be useful for the education and assessment of
      physicians in training. However, VR training is unable to override the impact of
      clinical training, although it may help shorten the learning curve early in
      training.

PMID- 15247758
TI  - Epidemiological and clinical behavior of prepubertal testicular tumors in Korea.
AB  - PURPOSE: To our knowledge there is no multi-institutional report on prepubertal
      testicular tumors in Korea to date. We obtained demographic data for a better
      understanding of the biological behavior and optimal management of these tumors.
      MATERIALS AND METHODS: The prepubertal testicular tumor registry form was mailed
      to all 87 hospitals registered in the Korean Urology Association. We
      retrospectively reviewed recent 5-year medical records. RESULTS: A total of 209
      patients were enrolled in this registry. The incidence was 0.98/100,000 children.
      Age was 1 to 142 months (median 18). Most patients were diagnosed with a scrotal
      mass before age 4 years. Serum alpha-fetoprotein and beta-human chorionic
      gonadotropin increased in as many as 62.9% and 2.7% of patients, including 94.7%
      and 2.2% in those with yolk sac tumor and 30.4% and 2.7% in those with teratoma,
      respectively. While potentially malignant tumors accounted for 52.5% of patients,
      the remainder were benign. Germ cell tumors were the most common (89.4% of
      cases), mainly with yolk sac tumor (47.8%) or teratoma (39.7%). Management after
      surgery included surveillance in 71.8% of cases, chemotherapy in 9.1%,
      combination therapy in 1.4% and other in 17.7%. Of the total patients 10.5% (5.9%
      of stage I yolk sac tumors) had progression to metastasis. The final results of
      treatment were complete remission (64.6% of cases), incomplete remission (2.9%),
      no response or disease progression (1.4%) and unknown (31.1%). Outcomes at the
      last followup (average 23.5 months) were 76.1% of patients alive, 0.9% dead and
      23.0% of unknown status. CONCLUSIONS: Demographic data on pediatric testicular
      tumors in Korea will lead to a better understanding of these rare tumors and to
      optimal therapy in these children.

PMID- 15247759
TI  - Hyperbaric oxygen therapy for cyclophosphamide induced refractory hemorrhagic
      cystitis in a child.

PMID- 15247760
TI  - Transperitoneal laparoscopic pyelolithotomy after failed percutaneous access in
      the pediatric patient.
AB  - PURPOSE: We present our experience with transperitoneal laparoscopic
      pyelolithotomy in pediatric patients in whom percutaneous renal access failed and
      the stone burden warranted open intervention. MATERIAL AND METHODS: A
      transperitoneal laparoscopic approach was used for pyelolithotomy in 8 patients 3
      months to 10 years old (mean age 4 years). Percutaneous access failed secondary
      to a nondilated system and/or an occluding lower pole calculus. Inclusion
      criteria were failed percutaneous access secondary to a nondilated system and/or
      stone occlusion of the lower pole system and failed shock wave lithotripsy or a
      stone burden of greater than 2.5 cm2. A posterior pelviotomy was made. Stones in
      the renal pelvis were removed with rigid graspers under direct laparoscopic
      vision. A flexible cystoscope was introduced through a port if caliceal stones
      were present. The renal pelvis was reconstructed. A watertight anastomosis was
      verified. RESULTS: Average operative time was 1.6 hours (range 0.8 to 2.3). Mean
      hospital stay was 2.15 days (range 2 to 3). A range of 1 to 3 stones (median of
      1) were removed and the mean stone burden was 2.9 cm2. No intraoperative
      complications were noted. Stone analysis revealed 3 patients with calcium oxalate
      stones, 1 with a calcium phosphate stone and 4 with cysteine stones. There was 1
      patient with stone recurrence at a mean followup of 12 months (range 3 to 20).
      Thus, the overall long-term stone-free rate was 87.5%. CONCLUSIONS:
      Transperitoneal laparoscopic pyelolithotomy is feasible when percutaneous access
      fails and open pyelolithotomy is considered due to a large stone burden.

PMID- 15247761
TI  - Does the endoscopic technique of ureterocele incision matter?
AB  - PURPOSE: Endoscopic ureterocele decompression is a well established procedure in
      children. However, an accurate endoscopic incision may be challenging in large
      ectopic ureteroceles. We describe a percutaneously assisted technique to
      facilitate the ease of ureterocele incision and review other described methods.
      MATERIALS AND METHODS: We reviewed the medical records of 12 children with
      ectopic ureteroceles subtending a double collecting system who underwent
      endoscopic, percutaneously assisted incision. Six ureteroceles were on the left
      side, 5 were on the right side and 1 child had bilateral ureteroceles.
      Decompression results were evaluated by ultrasound and Tc
      mercaptoacetyltriglycine imaging during a mean of 2.8 years of followup. RESULTS:
      There were 7 girls and 5 boys. Mean age at presentation was 11.6 months (range 1
      week to 6 years). The decompression success rate was 84% (11 of 13 renal units),
      and improved renal function and drainage was noted in 5 of 12 patients (41.6%).
      Seven of 12 patients had vesicoureteral reflux, of whom 2 were asymptomatic at
      followup and, hence, were treated conservatively. Five children underwent surgery
      because of recurrent urinary tract infections. CONCLUSIONS: Although our results
      are similar to those of other methods, percutaneously assisted cystoscopic
      incision of ureterocele enables easier and more accurate decompression. However,
      when comparing the various techniques described, it seems that postoperative
      results mostly reflect the anatomical and functional characteristics of the
      urinary system rather than the technique used.

PMID- 15247762
TI  - Pediatric renal injuries: management guidelines from a 25-year experience.
AB  - PURPOSE: We defined the mechanism and cause of pediatric renal trauma, and
      developed guidelines for management based on the outcome analysis of operative vs
      nonoperative management. MATERIALS AND METHODS: We retrospectively reviewed 374
      pediatric renal injuries at San Francisco General Hospital, comparing operative
      vs nonoperative management based on clinical presentation, type of renal injury,
      hemodynamic stability, associated injuries and the results of radiographic
      imaging. RESULTS: Blunt trauma accounted for 89% of pediatric renal trauma with a
      renal exploration rate of less than 2%. Penetrating trauma represented the
      remaining 11% with a renal exploration rate of 76%. Of grade IV renal injuries
      41% were successfully managed nonoperatively based on computerized tomography and
      staging in hemodynamically stable children. Our overall renal salvage rate was
      greater than 99%. CONCLUSIONS: Pediatric renal trauma is often minor and
      observation poses no significant danger to the child. In serious pediatric renal
      injuries early detection and staging based on clinical presentation and
      computerized tomography are critical for determining operative vs nonoperative
      management. Regardless of the type of management the standard of care is renal
      preservation (less than 1% nephrectomy rate in this series).

PMID- 15247763
TI  - Nerve injury after laparoscopic varicocelectomy.
AB  - PURPOSE: Laparoscopic varicocelectomy is a minimally invasive option for
      varicoceles in children. Occasional reports of nerve injury after inguinal
      laparoscopic procedures have been published. There is anatomical variation in the
      sensory innervation of the anterior thigh and variable branching patterns of the
      nerves involved. We report a retrospective analysis of our patients, focusing on
      the incidence of sensory changes on the ipsilateral anterior thigh after
      laparoscopic varicocelectomy. MATERIALS AND METHODS: The medical records of all
      patients who underwent laparoscopic varicocelectomy at 1 institution performed by
      2 of us (YR and DV) from 1997 to 2002 were retrospectively reviewed.
      Demographics, outcomes and any postoperative sensory complications were obtained
      by chart review and telephone interview. RESULTS: A total of 58 patients
      underwent laparoscopic varicocelectomy during this 5-year analysis and 51 with a
      total of 62 varicoceles were available for review. Three patients (4.8%)
      experienced transient numbness of the ipsilateral anterior thigh, which resolved
      or improved in an average of 8.0 months (range 6 to 9). Symptoms were not always
      noticed immediately postoperatively (range 0 to 10 days). In affected patients
      the sensory distribution was usually consistent with injury to the genitofemoral
      nerve. CONCLUSIONS: Laparoscopic varicocelectomy is a minimally invasive
      procedure that still has the potential for complications. Cautery or harmonic
      dissection of the peritoneum overlying the spermatic cord and excessive traction
      on the tissues surrounding the cord should be avoided intraoperatively. Patients
      and surgeons should be aware of the possibility of nerve injury and the resultant
      sensory deficit.

PMID- 15247764
TI  - Spontaneous resolution of high grade infantile vesicoureteral reflux.
AB  - PURPOSE: We studied the spontaneous resolution rate in a group of infants with
      high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or
      postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder
      dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS:
      This prospective study comprised 115 infants (80 boys and 35 girls) with high
      grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The
      majority of patients (71%) were diagnosed after UTI during infancy and only 26%
      were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were
      followed according to a program of repeat video cystometry and noninvasive 4-hour
      voiding observations. Median followup was 39 months. RESULTS: The overall
      spontaneous resolution rate to grade II or less for all grades was 39% with no
      difference between boys and girls. However, when comparing the more severe grades
      IV and V, we found a significantly higher resolution rate in boys during the
      infant year. No difference in VUR disappearance could be detected when comparing
      the groups according to presentation, prenatal ultrasound or pyelonephritis.
      Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and
      they significantly correlated with VUR nonresolution. Bladder dysfunction was
      found in 37% of patients and it also significantly correlated with nonresolution.
      CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V)
      congenital VUR was high in boys during the infant year (29%), whereas in girls
      and boys after the infant year the resolution rate was 9% yearly during followup.
      Negative prognostic factors for resolution were recurrent UTIs and bladder
      dysfunction.

PMID- 15247765
TI  - Colonic tubes for the antegrade continence enema: comparison of surgical
      technique.
AB  - PURPOSE: The Malone antegrade continence enema has revolutionized the management
      of intractable fecal incontinence and constipation. When the appendix is absent,
      surgical options are limited. Small series with short-term followup have
      demonstrated the feasibility but not the reliability of the continent colonic
      tube. We present our experience with a lateral based colonic tube. We also
      compared lateral based colonic tubes to medial based tubes. MATERIALS AND
      METHODS: The medical records of patients treated with a continent colonic tube
      for intractable fecal incontinence were reviewed. We identified 8 patients who
      underwent the procedure between July 2000 and February 2003. The literature was
      reviewed to compare lateral vs medial based tubes. RESULTS: Average followup was
      28 months (range 10 to 41). Stomal stenosis developed in 4 patients (50%) within
      3 to 6 months of surgery. Passive dilation at the clinic corrected the problem in
      3 patients and 1 required operative stomal revision. All 8 patients reported
      almost complete relief of rectal incontinence and constipation. A literature
      review demonstrated a significantly higher rate of stomal stenosis in lateral vs
      medial based colonic tubes (40% vs 12%). CONCLUSIONS: The continent colonic tube
      is a safe and effective alternative in patients with refractory fecal
      incontinence and constipation who do not have an available appendix. These
      results appear durable during the described period. We believe that this
      technique is an alternative to the cecostomy button and it should be offered to
      suitable patients. The lateral based colonic tube appears to have a higher rate
      of stomal stenosis than medial based colonic tubes, which may be attributed to
      the local blood supply of the colon.

PMID- 15247766
TI  - Long-term outcome analysis of Starr plication for primary obstructive
      megaureters.
AB  - PURPOSE: The Starr technique of tapering megaureters was first reported in 1979.
      Although this method of ureteral plication is well known, to our knowledge there
      are no clinical studies regarding outcomes. We report the first long-term outcome
      results with the Starr technique for primary obstructive megaureters. MATERIALS
      AND METHODS: Three girls and 10 boys with a total of 16 primary obstructive
      megaureters (3 bilateral) underwent reimplantation with Starr plication between
      1988 and 2000. Baseline and followup renal function (average followup 6.2 years)
      was determined with renal scan and/or 24-hour urinary creatinine clearance.
      Average age at operation was 5.6 years (range 2 months to 13 years). All ureters
      were plicated using the Starr technique with interrupted polydioxanone sutures
      performed by a single surgeon (CEH). Reimplantation methods were the Hendren
      technique in 7 and Politano-Leadbetter in 9. RESULTS: No ureter demonstrated
      obstruction postoperatively. One ureter refluxed, which resolved with subureteral
      collagen injection. Seven patients had mean preoperative and postoperative
      creatinine clearance +/- SD 72.9 +/- 14.8 and 102.1 +/- 10.9 cc per minute,
      respectively (p <0.05). Six patients underwent preoperative and postoperative
      renal scans. Average preoperative relative renal function on renal scan in the
      kidney with a megaureter was 53.0% +/- 6.7% (range 37% to 84%). Long-term
      followup (average 4.1 years) renal scan revealed a relative function of 53.3% +/-
      9.2% (range 37% to 100%). CONCLUSIONS: Our data demonstrate that Starr plication
      is a safe procedure that provides long-term stabilization of renal function in
      the management of primary obstructive megaureter.

PMID- 15247767
TI  - When can persistent hydroureteronephrosis in posterior urethral valve disease be
      considered residual stretching?
AB  - PURPOSE: Persistent hydroureteronephrosis (HUN) is often seen in boys with a
      history of a posterior urethral valve even years after valve ablation and it is
      often assumed to represent residual stretching. We determined the association of
      HUN with urodynamic abnormalities, the effect on HUN of treating these
      abnormalities and when persistent HUN could be considered residual stretching.
      MATERIALS AND METHODS: Of 71 patients with a posterior urethral valve evaluated
      after valve ablation 20 (28.2%) had persistent HUN in a total of 32 renal units
      (RUs). The degree of HUN was graded as mild, moderate or severe. Videourodynamics
      were performed in all patients with persistent HUN and abnormal urodynamic
      findings were aggressively treated. HUN was then reassessed and categorized as
      resolved, improved or unchanged. RESULTS: Abnormal urodynamic findings, primarily
      hypocompliance and instability, were noted in all 20 patients with HUN. All
      patients compliant with treatment showed dramatic improvement or complete
      resolution of abnormal urodynamic parameters. The 32 RUs with persistent HUN were
      initially graded as mild (8), moderate (13) and severe (11). HUN resolved in 15
      RUs and improved to a lower grade in 11 in 26 of the 27 RUs (96.3%) in the 17
      patients compliant with treatment. The 3 boys (5 RUs) who were noncompliant with
      treatment had neither decreased HUN nor improved urodynamic parameters. The 12 of
      27 RUs (44.4%) in the treatment group in which HUN failed to resolve completely
      had no distal ureteral obstruction or identifiable persistent urodynamic
      abnormality and, thus, they can be labeled as having residual stretching.
      CONCLUSIONS: Persistent HUN following valve ablation should not be considered
      residual dilatation until a thorough urodynamic evaluation has been done and any
      abnormal parameters are addressed. With correction of these abnormal parameters
      one can expect significant lessening of HUN and hopefully improved long-term
      preservation of renal function.

PMID- 15247768
TI  - Cost analysis of laparoscopic versus open orchiopexy in the management of
      unilateral nonpalpable testicles.
AB  - PURPOSE: Laparoscopic exploration for the nonpalpable testicle (NPT) has been
      criticized for increased costs compared with primary inguinal/scrotal
      exploration, mostly due to high equipment costs and the need for open
      inguinal/scrotal exploration in many cases. We assessed costs associated with
      diagnostic laparoscopy vs inguinal/scrotal exploration followed by selective open
      or laparoscopic treatment for unilateral NPT to identify the most important
      factors that influence cost. MATERIALS AND METHODS: A comprehensive literature
      review determined the probabilities of intra-abdominal or inguinal nubbins, blind
      ending vas/vessels and intra-abdominal or inguinal gonads in patients with
      unilateral NPT. The costs of anesthesia, equipment and operating room use were
      obtained from our institution or derived from the literature. A model was created
      using computer software to compare the costs of initial scrotal/inguinal approach
      or initial laparoscopic exploration in a theoretical population of boys with
      unilateral NPT. We established a set of assumptions and generated a series of 1
      way sensitivity analyses to detect cost influencing parameters. RESULTS: Based on
      the probabilities of intraoperative anatomical gonadal findings, use of reusable
      laparoscopic equipment and encompassing the ultimate surgical procedure needed
      initial laparoscopic evaluation was less costly than initial scrotal/inguinal
      exploration by 69 US dollars on a population basis. One-way sensitivity analyses
      showed that initial laparoscopic exploration was less costly if the operative
      time of laparoscopic exploration did not exceed 19 minutes and the cost of
      disposable laparoscopic equipment was less than 147 US dollars. CONCLUSIONS: On a
      population basis initial laparoscopic evaluation of the clinically nonpalpable
      testicle has a cost saving advantage (69 US dollars) over initial inguinal
      scrotal exploration when reusable laparoscopic equipment is primarily used,
      disposable equipment costs are kept low (147 US dollars or less) and operating
      room time for diagnostic laparoscopy are at national standards (19 minutes or
      less). These findings hold true for a wide range of probabilities and duration of
      inguinal exploration time. Given that all of these caveats are easily achievable,
      cost should not be used as a factor to bias against initial laparoscopic
      exploration.

PMID- 15247769
TI  - Impact of caveolin-1 expression on clinicopathological parameters in renal cell
      carcinoma.
AB  - PURPOSE: Caveolin-1 is a major structural component of caveolae, which are plasma
      membrane microdomains implicated in the regulation of intracellular signaling
      pathways. Previous studies of the expression and function of caveolin-1 in cancer
      have shown controversial results, indicating that the physiological role of
      caveolin-1 varies according to cancer type. We evaluated caveolin-1 expression in
      renal cell carcinoma and investigated its association with pathological features
      and clinical outcome. MATERIALS AND METHODS: Caveolin-1 expression was evaluated
      by immunohistochemistry using rabbit polyclonal antibody against caveolin-1 in 60
      paraffin embedded primary renal cell carcinoma specimens and 6 metastatic renal
      cell carcinoma specimens. When more than 50% of all cancer cell cytoplasm
      stained, the tumor was considered caveolin-1 positive. Associations between
      caveolin-1 expression, and pathological features and clinical outcomes were
      analyzed. RESULTS: Of 60 primary tumors 16 (26.7%) and 5 of 6 metastatic tumors
      (83.3%) were immunoreactive in more than 50% of cancer cells and considered
      caveolin-1 positive. Although no significant associations between caveolin-1
      expression, pathological stage (T stage) and distant metastasis at initial
      presentation were observed, significant associations between positive caveolin-1
      expression and high grade tumor (p = 0.0009) and regional lymph node metastasis
      at initial presentation (p = 0.0049) and venous invasion (p = 0.0195) were
      observed. There was no difference in cancer specific survival between caveolin-1
      positive and negative groups. However, in 43 patients without metastasis to
      regional lymph nodes or a distant site at initial presentation (N0M0) the
      caveolin-1 positive group had significantly shorter progression-free survival
      than the caveolin-1 negative group (p = 0.0332). CONCLUSIONS: Caveolin-1 over
      expression could be a common finding in aggressive forms of renal cell carcinoma.
      Caveolin-1 might have an important role in the invasion and metastatic
      progression of renal cell carcinoma.

PMID- 15247771
TI  - Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon
      198 variant.
AB  - PURPOSE: The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide
      dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify
      endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of
      GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder
      were tested. MATERIALS AND METHODS: Genotypes of the leucine (Leu) to proline
      (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val)
      polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56
      of MnSOD were determined by a polymerase chain reaction-restriction fragment
      length polymorphism technique in 213 patients and 209 normal controls. RESULTS:
      There was a significant difference in GPX1 genotype frequency between the case
      and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for
      the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p =
      0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly
      associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18,
      p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided
      no significant results. However, in men with at least 1 Ala MnSOD allele the risk
      associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to
      31.24, p = 0.024). CONCLUSIONS: The GPX1 Pro/Leu genotype may significantly
      increase the risk of bladder cancer and the increased risk may be modified by the
      Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease
      status of bladder cancer.

PMID- 15247772
TI  - Changes in epidermal growth factor receptor expression in human bladder cancer
      cell lines following interferon-alpha treatment.
AB  - PURPOSE: We examined the regulation of epidermal growth factor (EGF) receptor
      (EGFR) expression in human bladder cancer cell lines by interferon-alpha (IFN
      alpha), the ability of IFN-alpha to inhibit cell proliferation and the
      sensitivity of IFN-alpha pretreated cells to EGF. MATERIALS AND METHODS: Cell
      proliferation was determined using crystal violet colorimetric and clonogenic
      assays. EGFR expression was measured by flow cytometry using specific antibody or
      ligand binding approaches. RESULTS: After IFN-alpha (100 IU/ml) treatment cell
      surface EGFR expression was upregulated in 6 of 11 and down-regulated in 2 of 11
      bladder cancer cell lines. The over expression of cell surface EGFR peaked within
      48 to 96 hours and increased by 35% to 241% in individual cell lines. High level
      cell surface EGFR correlated with intracellular EGFR expression. Cell growth
      inhibition by IFN-alpha coexisted with EGFR over expression in the 6 lines. IFN
      alpha treated cells remained sensitive to EGF treatment. CONCLUSIONS: IFN-alpha
      transiently up-regulates EGFR expression and inhibits in vitro growth in some
      human bladder cancer cells. IFN-alpha does not prevent EGFR from binding EGF or
      signal transduction via the EGF-EGFR pathway. This may have clinical implications
      for improving treatment based on EGFR targeting in select patients with bladder
      cancer.

PMID- 15247770
TI  - Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer
      cells.
AB  - PURPOSE: Mitogen-activated protein kinases (MAPKs) comprise 3 subgroups, that is
      extracellular signal-regulated protein kinase, c-Jun N-terminal kinase (JNK) and
      p38 MAPK (p38). In this study we analyzed the role of JNK as well as the
      expression of MAPK phosphatase-1 (MKP-1) in renal cancers. MATERIALS AND METHODS:
      Four renal cell carcinoma (RCC) cell lines were used. The effects of anisomycin
      (JNK activator) and Ro-318220 (MKP-1 expression inhibitor) were analyzed by
      alamar blue assay. Apoptosis was determined by flow cytometric TUNEL analysis,
      nuclear morphological alternations and the detection of DNA fragmentation.
      Changes in MKP-1 expression as well as the activation of extracellular signal
      regulated protein kinases and JNK were analyzed by Western blotting. RESULTS: All
      cell lines treated with anisomycin resulted in a transient activation of JNK
      without inducing apoptosis. Since we hypothesized that elevated MKP-1 expression
      could possibly prevent persistent JNK activation, Ro-318220 was used. When cells
      were treated with Ro-318220, MKP-1 expression decreased in Caki-1 and KU 20-01
      cells but not in ACHN or 769P cells. Combined treatment of Caki-1 and KU 20-01
      cells with anisomycin and Ro-318220 resulted in a decrease in MKP-1 expression
      concomitant with persistent JNK activation. Apoptosis was induced in each cell
      line. CONCLUSIONS: These results suggest that prevalent MKP-1 expression in RCC
      contributes to cancer cell survival by attenuating an apoptosis inducing signal
      cascade via JNK. Since Ro-318220 potentiated JNK related apoptosis, JNK
      activation by blocking MKP-1 expression may be an effective therapeutic approach
      to RCC.

PMID- 15247773
TI  - Optical characteristics of the canine prostate at 665 nm sensitized with tin
      etiopurpurin dichloride: need for real-time monitoring of photodynamic therapy.
AB  - PURPOSE: Photodynamic therapy (PDT) is an emerging, minimally invasive therapy
      for prostate cancer that depends on the sequestration of a photosensitizing drug
      within targeted tissue. The photosensitizer is subsequently activated by light of
      a specific wavelength, resulting in destruction of the targeted tissue.
      Successful treatment requires knowledge of the optical properties of the target
      tissue, a critical element for therapy. MATERIALS AND METHODS: Adult canines were
      injected with tin etiopurpurin dichloride (1.0 mg/kg) as a liposome emulsion
      vehicle in saline 24 hours prior to light treatment. Laser light was delivered to
      the prostate via a 400 microm optical fiber fitted with a 2.0 cm cylindrical
      diffuser and optical properties of the prostate were measured. RESULTS: In this
      study we determined the attenuation coefficient and critical fluence in the
      canine prostate. Our studies shown that the attenuation coefficient is not
      uniform but higher at the base (average for all animals 2.59 to 2.79 cm-1) than
      in the mid section or apex of the prostate (1.71 to 1.90 cm-1). Significant
      differences among dogs (0.11 to 12.70 cm-1) were found. In some cases we observed
      a fluctuation of the attenuation coefficient during treatment. We also
      established experimentally the minimum energy (1449 mJ/cm2) needed (critical
      fluence) to produce necrosis. Experimentally establishing the values of effective
      attenuation and critical fluence is necessary to predict the area of ablation
      during PDT and protect surrounding organs from over treatment. CONCLUSIONS: Based
      on our results it is evident that for PDT of the prostate to be successful the
      optical parameters of the prostate must be measured and monitored during
      treatment. We suggest that the optimum way of doing this is real-time
      computerized monitoring combined with simulation PDT.

PMID- 15247774
TI  - Characteristics of adenosine triphosphate [corrected] release from porcine and
      human normal bladder.
AB  - PURPOSE: Although the sensory and motor roles of the purinergic system in the
      bladder are well proven in animal species, there is increasing evidence that it
      may have an important role in humans. In addition, it may be important in the
      pathophysiology of bladder dysfunction. We established the level of adenosine
      triphosphate (ATP) release from porcine and normal human bladders. MATERIALS AND
      METHODS: Bladder strips from patients with a urodynamically proven stable bladder
      undergoing surgery for stress incontinence and those undergoing cystectomy for
      cancer with no lower urinary tract symptoms were subjected to varying degrees of
      stretch (up to 50%) and electric field stimulation (10 to 40 Hz). A luciferase
      assay was used to quantify ATP release. RESULTS: Significantly increased ATP
      release over baseline was induced by mechanical and electrical stimulation (each
      p <0.05). Mean ATP release +/- SE from porcine bladders (38.2 +/- 1.9 pM/gm
      tissue following stretch and 19.9 +/- 6.5 pM/gm following electrical stimulation)
      was comparable to the release from human bladders (26.1 +/- 2.4 pM/gm tissue
      following stretch and 29.9 +/- 1.0 pM/gm following electrical stimulation). The
      main source of ATP release was the urothelium and not the muscle (p <0.05). This
      ATP release following stretch was not tetrodotoxin sensitive. CONCLUSIONS: The
      characteristics of ATP release from porcine and human bladders are similar and,
      therefore, the pig is a good model for humans. The main source of ATP release is
      urothelium from predominantly nonneuronal sources. This study supports a sensory
      role for ATP. An increased role for this purinergic neurotransmission may result
      in functional motor as well as sensory bladder disorders.

PMID- 15247775
TI  - Ca2+ sensitization in contraction of human bladder smooth muscle.
AB  - PURPOSE: The role of Ca2+ sensitization in the contraction of human bladder
      urinary smooth muscle (UBSM) was investigated. MATERIALS AND METHODS:
      Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and
      tension in fura-2 loaded intact strips and receptor coupled strips permeabilized
      with alpha-toxin were applied. Protein expressions was confirmed by Western blot
      analysis. RESULTS: In intact fura-2 loaded strips 1 microM carbachol (CCh)
      induced a greater contraction and a lower [Ca2+]i elevation than that induced by
      60 mM K depolarization. In alpha-toxin permeabilized strips 1 microM CCh induced
      contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i
      tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17
      proteins were expressed in human UBSM. In intact fura-2 loaded strips the
      application of 3 microM Y-27632, a ROCK inhibitor, or 3 microM
      bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the
      sustained phase of contraction induced by 1 microM CCh induced relaxation without
      changing [Ca2+]i. In alpha-toxin permeabilized strips the application of 3 microM
      Y-27632 or 3 microM GF109203X during the sustained contraction induced by 0.3
      microM Ca plus 10 microM guanosine triphosphate and 1 microM CCh induced
      relaxation at constant [Ca2+]i. CONCLUSIONS: These results indicate that in human
      UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by
      increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK and
      protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may
      represent an alternative target in the treatment of overactive bladder.

PMID- 15247776
TI  - Characterization of the control of intracellular [Ca2+] and the contractile
      phenotype of cultured human detrusor smooth muscle cells.
AB  - PURPOSE: We measured the functional properties of cultured human detrusor
      myocytes with respect to their ability to regulate their intracellular [Ca2+] and
      generate force in collagen matrices. MATERIALS AND METHODS: Human detrusor
      biopsies were dissociated into single cells by collagenase treatment and used
      immediately or cultured in D-valine medium and subsequently used after culture
      trypsinization. Intracellular [Ca2+] was measured in Fura-2 loaded myocytes. Cell
      force development was measured by incorporating cells into a collagen gel and
      attaching it to an isometric strain gauge. RESULTS: Carbachol was equally
      effective in generating Ca transients in freshly isolated and cultured cells.
      Carbachol potency (pEC50) and the magnitude of Ca2+ transients were similar.
      Adenosine triphosphate potency was decreased in cultured cells and Ca2+
      transients showed properties consistent with a purinoceptor shift from a
      purinergic subtype. Temporal restitution of Ca2+ transients was similar in the 2
      groups, indicative of retained intracellular Ca2+ stores in cultured cells.
      Cultured cells (approximately 10(6)) embedded in collagen gel generated a force
      about 10 times greater than that generated by gel alone. The cell dependent force
      could be further increased by adding carbachol. CONCLUSIONS: Cultured cells
      retain the ability to generate agonist induced intracellular Ca2+ transients.
      There was no evidence that the cell culture altered the properties of muscarinic
      receptors, although purinoceptor mediated properties were altered. Restitution
      experiments indicated that functional intracellular Ca2+ stores were retained in
      cultured cells. Cultured cells also retained a contractile phenotype, especially
      in response to carbachol. The magnitude of force was attenuated, which may be a
      function of the biomechanical properties of the gel used to embed the cells.

PMID- 15247778
TI  - Shape retaining injectable hydrogels for minimally invasive bulking.
AB  - PURPOSE: Particle migration, poor shape definition and/or rapid resorption limit
      the success of current urethral bulking agents. We propose that shape defining
      porous scaffolds that allow cell infiltration and anchoring, and may be delivered
      in a minimally invasive manner may provide many advantageous features. MATERIALS
      AND METHODS: Alginate hydrogels were prepared with varying degrees of covalent
      cross-linking and different pore characteristics. Dehydrated scaffolds were
      compressed into smaller, temporary forms, introduced into the dorsal subcutaneous
      space of CD-1 mice by minimally invasive delivery through a 10 gauge
      angiocatheter and rehydrated in situ with a saline solution delivered through the
      same catheter. Ionically cross-linked calcium alginate gel served as a control.
      Specimens were harvested at 2, 6, 12 and 24 weeks to evaluate implant shape
      retention and volume, cell infiltration and calcification, and the presence of an
      inflammatory response. RESULTS: A total of 90 scaffolds were implanted and 95%
      were recovered at the site of injection. All of these scaffolds successfully
      rehydrated and 80% recovered and maintained their original 3-dimensional shape
      for 6 months. Scaffold volume and tissue infiltration varied depending on the
      degree of alginate cross-linking. Highly cross-linked materials (20% and 35%)
      demonstrated the best volume maintenance with the latter facilitating the most
      tissue infiltration. The inflammatory response was minimal except with the 80%
      cross-linked material. Calcification was not observed in covalently cross-linked
      scaffolds. In contrast, 98% of calcium alginate implants were calcified.
      CONCLUSIONS: Shape retaining porous hydrogels meet many of the requirements
      necessary for a successful injectable bulking agent and offer advantages over
      currently used agents.

PMID- 15247777
TI  - Effects of alpha 1-adrenergic receptor subtype selective antagonists on lower
      urinary tract function in rats with bladder outlet obstruction.
AB  - PURPOSE: Antagonists of alpha 1-adrenergic receptors (alpha 1ARs) relieve
      obstructive and irritative symptoms in patients with bladder outlet obstruction.
      However, to our knowledge mechanisms underlying the relief of irritative symptoms
      remain unknown. Because bladder alpha 1dARs are up-regulated in some rats with
      bladder outlet obstruction, we investigated the effect of the alpha 1aAR
      antagonist 5-methyl urapidil (5MU) vs the alpha 1a/alpha 1dAR antagonist
      tamsulosin on urinary frequency in obstructed rats. MATERIALS AND METHODS:
      Baseline frequency was measured using a chronic micturition recording system and
      then obstruction (40 rats) or sham obstruction surgery (11 rats) was performed.
      After 6 weeks frequency was reassessed, followed by subcutaneous implantation of
      osmotic pumps to deliver 5MU, tamsulosin or vehicle for 1 week. Upon the
      completion of drug treatment urinary frequency was again measured and the pressor
      response to the alpha 1AR agonist phenylephrine was documented. RESULTS:
      Obstructed bladder mass was an average of 4.9 times greater than bladder mass in
      sham operated rats (p <0.001). Urinary frequency was elevated in obstructed rats
      with a bladder mass of greater than 500 mg vs all rats with a bladder mass of
      under 255 mg (p = 0.01). Of rats with a bladder mass of greater than 500 mg
      frequency was decreased in those treated with tamsulosin (p = 0.03) but not in
      those treated with 5MU. Tamsulosin and 5MU inhibited the pressor response to
      phenylephrine. CONCLUSIONS: Urinary frequency is increased in rats with a bladder
      mass of greater than 500 mg. The combined alpha 1a/alpha 1dAR antagonist
      tamsulosin decreases urinary frequency more than the alpha 1aAR selective
      antagonist 5MU. This finding supports the hypothesis that the alpha 1dAR is
      important for mediating irritative symptoms.

PMID- 15247779
TI  - Cajal-like cells in the human upper urinary tract.
AB  - PURPOSE: Interstitial cells of Cajal (ICCs) have an important role in the
      regulation of gut motility as they are responsible for the slow wave activity of
      smooth muscle. It is still unknown if ICCs also occur in the human upper urinary
      tract. Since these cells express and are marked by the c-kit receptor CD117, we
      investigated its occurrence and distribution along the human upper urinary tract.
      MATERIALS AND METHODS: Tissues from 56 human ureters, spanning proximal, middle
      and distal ureter segments, were analyzed by indirect immunohistochemistry using
      the alkaline phosphatase-anti-alkaline phosphatase method and double labeling
      immunofluorescence on consecutive tissue sections. Several monoclonal and
      polyclonal antibodies to c-kit receptor were used in combination with various
      cell markers for histiocytic, mast cell, endothelial, epithelial, neuronal,
      smooth muscle and stem cell differentiation. RESULTS: The c-kit receptor was
      found in 3 cell types of the ureter and in round or spindle-shaped cells. Due to
      their antigenic profile the first one was revealed as mast cells occurring in all
      layers of the ureteral wall except the urothelium. In contrast, the population of
      spindle-shaped cells was only marked by c-kit receptor, thus, resembling ICCs.
      These ICC-like cells were found among the inner and outer smooth muscle layers,
      and in the lamina propria. They showed a slight decrease from proximal to distal
      ureteral segments. However, unlike intestinal ICCs their cytomorphology differed
      and some cells, representing the third group of c-kit receptor positive cells,
      were found within the urothelium. CONCLUSIONS: Our data demonstrate the presence
      of ICC-like cells and their ubiquitous distribution in the human ureter. The
      physiological importance and pathological significance of these findings must be
      evaluated by functional studies and investigations of certain pathological with
      urinary outflow disturbance conditions.

PMID- 15247780
TI  - Re: Comparison of hand assisted and standard laparoscopic radical
      nephroureterectomy for the management of localized transitional cell carcinoma.

PMID- 15247782
TI  - Re: The effects of combined androgen blockade on cognitive function during the
      first cycle of intermittent androgen suppression in patients with prostate
      cancer.

PMID- 15247784
TI  - Re: Successful transfer of open surgical skills to a laparoscopic environment
      using a robotic interface: initial experience with laparoscopic radical
      prostatectomy.

PMID- 15247785
TI  - Re: An evaluation of the decreasing incidence of positive surgical margins in a
      large retropubic prostatectomy series.

PMID- 15247786
TI  - Re: An evaluation of the decreasing incidence of positive surgical margins in a
      large retropubic prostatectomy series.

PMID- 15247787
TI  - Re: Metabolic evaluation of 94 patients 5 to 16 years after ileocecal pouch
      (Mainz pouch 1) continent urinary diversion.

PMID- 15247788
TI  - Re: Surgical intervention for complications of the tension-free vaginal tape
      procedure.

PMID- 15247789
TI  - Re: Noninvasive techniques for the measurement of isovolumetric bladder pressure.

PMID- 15247791
TI  - Re: Body size and serum levels of insulin and leptin in relation to the risk of
      benign prostatic hyperplasia.

PMID- 15247792
TI  - Re: Safer transurethral resection of the prostate: coagulating intermittent
      cutting reduces hemostatic complications.

PMID- 15247793
TI  - Re: initial evaluation of robotic technology for microsurgical vasovasostomy.

PMID- 15247797
TI  - Medical surveillance in biotechnology research laboratories: is there a need for
      special medical check-ups?

PMID- 15247798
TI  - Re: Symptom magnification and neurocognitive dysfunction.

PMID- 15247800
TI  - Using the hierarchy of control technologies to improve healthcare facility
      infection control: lessons from severe acute respiratory syndrome.
AB  - Health care facilities need to review their infection control plans to prepare
      for the possible resurgence of severe acute respiratory syndrome, other emerging
      pathogens, familiar infectious agents such as tuberculosis and influenza, and
      bioterrorist threats. This article describes the classic "hierarchy of control
      technologies" that was successfully used by occupational and environmental
      medicine professionals to protect workers from illness and death during the
      resurgence of tuberculosis in the 1990s. Also discussed are related guidelines
      from building and equipment professional organizations and novel infection
      control techniques used successfully by various hospitals in Asia, Canada, and
      the United States during the 2003 severe acute respiratory syndrome epidemic.
      Taken together, they suggest a framework upon which a comprehensive infection
      control plan can be crafted to prevent the spread of deadly infectious agents to
      health care workers (clinicians and paraprofessionals), uninfected patients and
      visitors.

PMID- 15247801
TI  - Effectiveness of a healthy work organization intervention: ethnic group
      differences.
AB  - This study examined ethnic group differences in the effectiveness of a healthy
      work organization intervention on organizational climate and worker health and
      well-being. Our sample consisted of employees from 21 stores of a large national
      retail chain. The intervention involved establishing and facilitating employee
      problem-solving teams in 11 of the stores. Teams were charged with developing and
      implementing action plans tailored to the needs of their specific site. Pre- and
      postcomparisons of the treatment and control groups showed that the intervention
      produced positive effects on both the climate and health and well-being outcomes;
      however, these effects varied significantly by ethnic group. Particularly in
      terms of organizational climate, black and Hispanic employees were the primary
      beneficiaries of the participatory intervention process. These results are
      interpreted in terms of social identification and self-categorization theories
      and are contrasted with traditional participatory and diversity training
      approaches.

PMID- 15247802
TI  - The application of two health and productivity instruments at a large employer.
AB  - We applied two productivity instruments (the Work Productivity Short Inventory
      and the Work Limitations Questionnaire) to the same employees working at a large
      telecommunications firm. In this work we note differences in productivity metrics
      obtained from these instruments and offer reasons for those differences that may
      be related to their design. Within this sample, average at-work productivity
      (presenteeism) losses were 4.9% as measured by the WLQ and 6.9% as measured by
      the WPSI. These translated into losses of approximately $2000 to $2800 per
      employee per year, respectively. Total productivity losses were usually not
      associated with demographics or job type but were associated with perceived
      health status and the existence of particular medical conditions. Both
      instruments may be useful for employers who want to estimate productivity losses
      and learn where to focus their energy to help stem those losses.

PMID- 15247803
TI  - A prospective assessment investigating the relationship between work productivity
      and impairment with premenstrual syndrome.
AB  - Our objective was to assess life domain and work-related impairment in patients
      experiencing premenstrual syndrome (PMS). A sample of women, 18 to 45 years of
      age, completed the Daily Rating of Severity of Problems Form to record daily
      symptoms for two consecutive menstrual cycles. In the workplace, women with PMS
      reported higher absenteeism rates (2.5 days vs. 1.3 days; P = 0.006) and more
      workdays with 50% or less of typical productivity per month (7.2 days vs. 4.2
      days; P < 0.0001). Women with PMS in one of two menstrual cycles reported a
      greater number of days with impairment in routine work, school, and household
      activities in comparison with women without PMS. Results indicate that PMS leads
      to substantial im in normal daily activities and occupational productivity and
      significantly increased work absenteeism.

PMID- 15247805
TI  - Cement dust exposure and ventilatory function impairment: an exposure-response
      study.
AB  - We investigated cumulative total cement dust exposure and ventilatory function
      impairment at a Portland cement factory in Tanzania. All 126 production workers
      were exposed. The control group comprised all 88 maintenance workers and 32
      randomly chosen office workers. Exposed workers had significantly lower forced
      vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak
      expiratory flow rate (PEF), FEV1/FVC, FVC%, FEV1% and PEF%, than controls
      adjusted for age, duration of employment, height, and pack-years. Cumulative
      total dust exposure was significantly associated with reduced FVC, forced
      expiratory volume in 1 second, and peak expiratory flow rate adjusted for age,
      height and pack-years. Cumulative total dust exposure more than 300 mg/m year
      versus lower than 100 mg/m years was significantly associated with increased risk
      of developing airflow limitation (odds ratio = 9.9). The current occupational
      exposure limit for total cement dust (10 mg/m) appears to be too high to prevent
      respiratory health effects among cement workers.

PMID- 15247806
TI  - Terrorism-preparedness training for non-clinical hospital workers: tailoring
      content and presentation to meet workers' needs.
AB  - Clinicians have been the primary focus of health care worker training in response
      to the 2001 terrorist and anthrax attacks. However, many nonclinical hospital
      workers also are critical in providing medical care during any large-scale
      emergency. We designed a training program, guided by focus groups, to provide
      them with information to recognize unusual events and to protect themselves. We
      compared four different training methods: workbook, video, lecture, and a small
      group discussion. One hundred and ninety-one workers participated. After the
      training, they were more confident in their employer's preparedness to respond to
      a terrorist attack but specific knowledge did not change substantially.
      Fortunately, the self-directed workbook (the more economical and least disruptive
      method) was as effective as the other methods. Our experience may be useful to
      others who are planning terrorism-preparedness training programs.

PMID- 15247807
TI  - Differences in mortality by radiation monitoring status in an expanded cohort of
      Portsmouth Naval Shipyard workers.
AB  - Studies of leukemia and lung cancer mortality at the Portsmouth Naval Shipyard
      (PNS) have yielded conflicting results. In an expanded cohort of PNS workers
      employed between 1952 and 1992 and followed through 1996, the all-cause
      standardized mortality ratio (SMR) was 0.95 (95% confidence interval, 0.93-0.96).
      Employment duration SMRs were elevated with confidence intervals excluding 1.00
      for lung cancer, esophageal cancer, and all cancers combined. Leukemia mortality
      was as expected overall, but standardized rate ratio analyses showed a
      significant positive linear trend with increasing external radiation dose. The
      role of solvent exposures could not be evaluated. Findings differed by radiation
      monitoring subcohort, with excess asbestosis deaths limited to radiation workers
      and several smoking-related causes of death higher among nonmonitored workers. At
      PNS, asbestos exposure and possibly smoking could be nonrandomly distributed with
      respect to radiation exposure, suggesting potential for confounding in internal
      analyses of an occupational cohort.

PMID- 15247808
TI  - Mortality update of workers exposed to acrylonitrile in The Netherlands.
AB  - To study the possible carcinogenic effects of acrylonitrile, we updated the
      follow up of a cohort of 2842 acrylonitrile workers. The comparison group
      consisted of 3961 workers from a nitrogen fixation plant. Industrial hygiene
      assessments quantified past exposure to acrylonitrile, 8-hour averages as well as
      peak exposure, the use of personal protective equipment, and exposure to other
      potential carcinogenic agents. Standardized mortality ratios were calculated to
      adjust for the effect of age distribution, length of follow up, and temporal
      changes in background mortality rates. Cumulative dose-effect relations were
      determined for 3 exposure categories and 3 latency periods. The results show that
      no cancer excess seems related to exposure to acrylonitrile. This additional
      follow up of a cohort of 2842 workers exposed to acrylonitrile further supports
      the notion that occupational exposures to acrylonitrile that have occurred in the
      past have not noticeably increased workers' cancer mortality rates.

PMID- 15247809
TI  - Impact of one year of shift work on cardiovascular disease risk factors.
AB  - The purpose of the study was to investigate whether the reported increased
      cardiovascular disease risk in shift workers could be explained by changes in
      cardiovascular risk factors. In a cohort of 239 shift and 157 daytime workers, 1
      year changes in biological and lifestyle cardiovascular risk factors were
      monitored between the start of a new job and 1 year later. Both body mass index
      and low-density lipoprotein/high-density lipoprotein cholesterol ratio decreased
      significantly in shift workers compared with daytime workers (body mass index
      change: -0.31 and +0.13 kg/m; low-density lipoprotein/high-density lipoprotein
      ratio change: -0.33 and -0.13 respectively). Cigarettes smoked per day increased
      significantly in shift compared with daytime workers (+1.42 and -1.03,
      respectively). Therefore, only for smoking, an unfavorable change was observed.
      This may explain, at most, only a part of the excess cardiovascular disease risk
      reported in shift workers.

PMID- 15247810
TI  - Hepatic effects in workers exposed to 2-methoxy ethanol.
AB  - The objective of this study was to investigate the effects of 2-ME on hepatic
      function in exposed workers. Fifty-three impregnation workers from two copper
      clad laminate-manufacturing factories using 2-ME as a solvent were recruited as
      the exposed group. Another group of 121 lamination workers with indirect exposure
      to 2-ME was recruited as the comparison group. Environmental monitoring of air 2
      ME concentrations and biological monitoring of urine 2-methoxy acetic acid
      concentrations were performed. Venous blood was collected for blood biochemistry
      analyses. Liver function examination results showed that the aspartate amino
      transferase, alanine amino transferase, and gamma-glutamyl transferase in the 2
      ME-exposed workers were not significantly different from those in the comparison
      workers. After adjustment for hepatitis carrier status, gender, body mass index,
      and duration of employment, no difference were found between exposed and
      comparison groups. We conclude that 2-ME was not a hepatotoxin.

PMID- 15247811
TI  - Preplacement nerve testing for carpal tunnel syndrome: is it cost effective?
AB  - Is not hiring otherwise-qualified workers who have an abnormal post-offer
      preplacement (POPP) median nerve test a cost-effective strategy to reduce
      workers' compensation expenses related to carpal tunnel syndrome (CTS)? We
      performed a retrospective dynamic cohort study based on 2150 workers hired at a
      company between January 1996 and December 2001 and who underwent POPP median
      nerve testing. Workers were followed until they left the company or until follow
      up ended in May 2003. RESULTS: Thirty-five cases of work-related CTS occurred
      during follow-up, and 9.13 cases could have been avoided. However, if the company
      had not hired workers with abnormal POPP nerve test results, it would have
      suffered a net loss of $357,353. CONCLUSION: Not hiring workers with abnormal
      POPP nerve tests to reduce costs of work-related CTS is not a cost-effective
      strategy for employers.

PMID- 15247812
TI  - Blood lead levels in U.S. workers, 1988-1994.
AB  - Limited research has been conducted to measure the association between elevated
      blood lead levels and sociodemographic factors among U.S. workers in various
      industries and occupations using population-based survey data. Data from the
      Third National Health and Nutrition Examination Survey ( n = 10,127) were used to
      determine the blood lead levels in the U.S. workers. The prevalence of elevated
      blood lead levels > or = 50 microg/dL was 0.001% (1560) among U.S. workers
      compared with 0.2% (19,953) workers with elevated lead levels > or = 40
      microg/dL. Regression analyses indicated that workers in the repair service
      industry were correlated with higher blood lead levels than those workers in the
      construction industry. Although low blood lead levels were found for the entire
      working population, the results showed that there were still high blood lead
      levels in certain occupations and industries during 1988 to 1994.

PMID- 15247813
TI  - Evaluation of current biological exposure index for occupational N, N
      dimethylformamide exposure from synthetic leather workers.
AB  - The aim of this study was (1) to investigate the correlation between external
      exposure to N, N-dimethylformamide (DMF) and urinary excretion of DMF and N
      methylformamide; (2) to assess whether the correspondence between the current
      occupational exposure limit setting and recommended urinary biological exposure
      index is substantial; and (3) to evaluate whether coexposure to toluene, methyl
      ethyl ketone, and ethyl acetate has an effect on urinary excretion of DMF and N
      methylformamide (NMF). Urinary DMF and NMF were significantly correlated (P <
      0.01) with one another and also significantly correlated with airborne DMF (P <
      0.01) over the range of 1.55 to 152.8 mg/m. Urinary DMF can be considered a
      complementary marker for short-term exposure. Urinary concentration of NMF and
      DMF, corresponding to the 8-hour exposure to airborne DMF at 30 mg/m, was
      estimated to 38.4 mg/L or 39.4 mg/g creatinine for NMF and to 0.92 mg/L or 0.96
      mg/g creatinine for DMF.

PMID- 15247814
TI  - The relationship between health risks and work productivity.
AB  - We sought to provide evidence for the relationship between health risks and self
      reported productivity, including health-related absence and impaired performance
      on the job. A cross-sectional analysis was implemented consisting of 2264
      employees of a large national employer located in the Northeast. Participants
      responded to a health risk assessment and work productivity scale. Mean
      productivity loss was compared for individuals with different levels of risk
      factors using analysis of variance. Multivariate analyses, including logistic and
      linear regression, were used to determine the significance of health risks on
      productivity loss. Participants with more risk factors reported greater
      productivity loss (P < 0.001). The odds of any productivity loss were most
      significant for individuals with diabetes (absenteeism) and stress
      (presenteeism). In conclusion, higher risks are strongly associated with greater
      productivity loss, and different risks are associated with absenteeism than with
      presenteeism.

PMID- 15247815
TI  - Change in health risks and work productivity over time.
AB  - We sought to examine the relationship between changes in health risks and changes
      in work productivity. Pre- and postanalysis was conducted on 500 subjects who
      participated in a wellness program at a large national employer. Change in health
      risks was analyzed using McNemar chi-square tests, and change in mean
      productivity was analyzed using paired t tests. A repeated measures regression
      model examined whether a change in productivity was associated with a change in
      health risks, controlling for age and gender. Individuals who reduced one health
      risk improved their presenteeism by 9% and reduced absenteeism by 2%, controlling
      for baseline risk level, age, gender, and interaction of baseline risk and risk
      change. In conclusion, reductions in health risks are associated with positive
      changes in work productivity. Self-reported work productivity may have utility in
      the evaluation of health promotion programs.

PMID- 15247816
TI  - Question: What criteria are disqualifying for a driver undergoing a Department of
      Transportation medical evaluation?

PMID- 15247820
TI  - Acute care management of post-TBI spasticity.
AB  - The management of persons with traumatic brain injury (TBI) who have acute
      spasticity remains a challenge. A correct stratification is essential to clinical
      care and determination of efficacy from proposed interventions. The secondary
      severe sequelae of spasticity after TBI can result in profound functional
      impairment. These concerns are often best addressed early in the patient's
      course. Limited research in the area of the acute care treatment of severe
      spasticity is available. The authors employ a review of the available data as
      well as recount their own clinical experience in the acute care management of
      severe spasticity to assist in developing an order for the plethora of potential
      treatments available to clinicians and researchers. We propose to use a case
      example to emphasize key clinic points in the management of spasticity in the
      acute care setting.

PMID- 15247821
TI  - Orally delivered baclofen to control spastic hypertonia in acquired brain injury.
AB  - To determine if oral/systemic delivery of baclofen can effectively decrease
      spastic hypertonia due to acquired brain injury (traumatic brain injury, stroke,
      anoxia, or encephalopathy). Tertiary care outpatient rehabilitation center
      directly attached to a university hospital. Patients were a convenience sample
      recruited consecutively who had been referred for treatment of their spastic
      hypertonia to our spasticity clinic over a 5-year period. The spastic hypertonia
      was due to an acquired brain injury by either traumatic brain injury (TBI),
      stroke, or anoxic brain injury. All patients were more than 6 months postinjury
      or illness. Retrospective review of patients before and after initiation of
      treatment with oral baclofen, per standardized clinical data sheets. Thirty-five
      patients (22 TBI patients) were started on oral baclofen and were reevaluated
      between 1 to 3 months after initiation of treatment. Data for motor tone
      (Ashworth scores), spasm scores (Penn spasm frequency score), and deep tendon
      reflex scores were collected on the affected upper extremity (UE) and lower
      extremity (LE) side(s). Normal extremities were not assessed. Differences over
      time were assessed via descriptive statistics and Wilcoxon signed-rank. After 1
      to 3 months of treatment when subjects had reached their maximal tolerated
      dosage, the average LE Ashworth score in the affected lower extremities (LEs)
      decreased from 3.5 to 3.2 (P =.0003), the reflex score decreased from 2.5 to 2.2
      (P =.0274), and there was no statistical difference in the spasm score (P >.05).
      When the 22 TBI patients are analyzed separately, the average LE Ashworth score
      decreased from 3.5 to 3.2 (P =.0044) and the reflex score decreased from 2.7 to
      2.0 (P =.0003). There was no statistically significant change in UE tone, spasm
      frequency, or reflexes after 1 to 3 months of treatment (P >.05). The average
      dosage at follow-up was 57 mg/day of baclofen (range 15-120 mg/day). There was a
      17% incidence of somnolence that limited the maximum daily dosage of the
      medication. The oral delivery of baclofen is capable of reducing LE spastic
      hypertonia resulting from acquired brain injury. The lack of effect upon the
      upper extremities may be due to receptor specificity issues. GABA-B receptors may
      be less involved in the modulation of UE spastic hypertonia.

PMID- 15247822
TI  - Evaluation and management of spastic gait in patients with traumatic brain
      injury.
AB  - Damage to the corticospinal system after brain injury interferes with activities
      of daily living, mobility, and communication. The chief cause of this
      interference has to do with impairment to produce and regulate voluntary movement
      accompanied by the presence of spasticity. This review advocates that the
      evaluation of "spasticity" should focus on 3 issues: (1) identifying the clinical
      pattern of motor dysfunction and its source; (2) identifying the patient's
      ability to control muscles involved in the clinical pattern; and (3) the
      differential role of muscle stiffness and contracture as it relates to the
      functional problem. We have identified and described 6 clinical patterns of motor
      dysfunction affecting the lower limbs during gait, found in patients with
      traumatic brain injury and residual from upper motor neuron lesions. We have
      presented the use of dynamic electromyography to identify the voluntary and
      spastic characteristics of individual muscles in gait and the use of anesthetic
      nerve blocks to identify properties of stiffness and contracture in particular
      muscle groups. Treatment algorithms for these problems include identification of
      the muscles that contribute to the deformity across a joint; the stage of patient
      recovery; and most important, the clinical goals applicable to the patient. The
      treatment strategies based on the algorithm included in this article were focused
      on the use of chemodenervation of targeted muscles, neuro-orthopedic surgery, and
      other therapeutic strategies.

PMID- 15247823
TI  - Choosing upper limb muscles for focal intervention after traumatic brain injury.
AB  - The upper motoneuron syndrome (UMNS) resulting from lesions of corticospinal
      pathways is an important source of disability after traumatic brain injury (TBI).
      Classic expressions of motor behavior in UMNS are of 2 kinds: (1) manifestation
      of muscle underactivity, termed negative signs, and (2) manifestation of a
      variety of forms of muscle overactivity, termed positive signs. Combinations of
      negative and positive signs give rise to clinical patterns of movement
      dysfunction such as the flexed elbow, the clenched fist, and the thumb-in-palm
      deformity. These clinical patterns can be viewed as reflecting a net balance of
      muscle forces acting across the joints of a limb. Individual muscles are amenable
      to a variety of focal interventions such as neurolysis, chemodenervation, or
      surgery. Since more than one muscle acts across most joints, choices among
      muscles for focal intervention are many. This article will focus on focal
      interventions of upper limb muscles of patients with TBI who have UMNS and will
      explore the theme of choosing upper limb muscles for focal interventions after
      TBI.

PMID- 15247824
TI  - Neuro-orthopedic management of shoulder deformity and dysfunction in brain
      injured patients: a novel approach.
AB  - Shoulder problems are common in patients with traumatic brain injury. Very little
      has been written about the evaluation and neuro-orthopedic management of these
      problems. This is largely because there have not been surgical treatments
      available other than release of contracted, nonfunctional shoulders. Shoulder
      problems can be classified and evaluated using several different strategies: bony
      versus soft tissue restrictions; static versus dynamic deformities; traumatic
      injuries versus impairments secondary to weakness and spasticity; or problems of
      active function versus problems of passive function. Regardless of the
      classification system employed a systematic approach to evaluation and treatment
      is essential. Shoulder impairments can be corrected leading to significant
      improvement in functional outcomes. In this paper we report on the novel
      evaluation and surgical management options developed in our program for the most
      common shoulder problems encountered in patients with traumatic brain injury.

PMID- 15247825
TI  - Outcome assessment for spasticity management in the patient with traumatic brain
      injury: the state of the art.
AB  - The objective of this article was to (1) review the engineering and medical
      literature to structure the available information concerning the assessment of
      spasticity in the neurological population; (2) to discuss the strengths and
      weaknesses of the different methods currently in use in spasticity assessment;
      and (3) make recommendations for future efforts in spasticity outcome assessment.
      Spasticity textbooks, Web sites, and OVID, IEEE, and Medline searches from 1966
      through 2003 of spasticity, quantitative measure, or outcome assessment in the
      rehabilitation population were used as data sources. Over 500 articles were
      reviewed. Articles that discussed outcome measures used to assess interventions
      and evaluation of spasticity were included. Authors reviewed the articles looking
      at inclusion criteria, data collection, methodology, assessment methods, and
      conclusions for validity and relevance to this article. Issues such as clinical
      relevance, real-world function and lack of objectivity, and time consumed during
      performance are important issues for spasticity assessment. Some measures such as
      the Ashworth Scale remain in common use secondary to ease of use despite their
      obvious functional limitations. More functional outcome goals are plagued by
      being more time consuming and a general inability to demonstrate changes after an
      intervention. This may be secondary to the other factors that combine with
      spasticity to cause dysfunction at that level. Quantitative metrics can provide
      more objective measurements but their clinical relevance is sometimes
      problematic. The assessment of spasticity outcome is still somewhat problematic.
      Further work is necessary to develop measures that have real-world functional
      significance to both the individuals being treated and the clinicians. A lack of
      objectivity is still a problem. In the future it is important for clinicians and
      the engineers to work together in the development of better outcome measures.

PMID- 15247826
TI  - Research on minimally conscious patients: innovation or exploitation?

PMID- 15247827
TI  - A new neuropsychological test battery: the NAB.

PMID- 15247828
TI  - Anterior pituitary dysfunction after traumatic brain injury, part II.

PMID- 15247832
TI  - Vascular endothelial growth factor overexpression increases vascularization by
      murine but not human endothelial cells in cultured skin substitutes grafted to
      athymic mice.
AB  - Cultured skin substitutes (CSS) consisting of fibroblasts, keratinocytes, and
      biopolymers are an adjunctive treatment for large burns. Because CSS lack a
      vascular plexus, they vascularize more slowly than split-thickness autografts.
      Previously, CSS were prepared with dermal microvascular endothelial cells (ECs),
      which formed vascular analogs at a low frequency but did not contribute to
      increased vascularization after grafting. The present study addressed whether
      keratinocytes genetically modified to overexpress vascular endothelial growth
      factor (VEGF), an endothelial cell mitogen, could improve the persistence and
      organization of ECs in CSS. CSS were prepared with control or VEGF-modified
      keratinocytes, with (CSS + ECs) or without added ECs, and were grafted to full
      thickness wounds in athymic mice. Elevated VEGF expression was detected in VEGF
      modified CSS and CSS + ECs compared with controls, but no significant difference
      in EC density in vitro was observed. After grafting, VEGF-modified CSS and CSS +
      ECs showed enhanced vascularization, and organization of human ECs into
      multicellular structures in CSS + ECs was observed. However, VEGF overexpression
      did not significantly enhance the proliferation of human ECs, suggesting that
      other factors may be required. Improved persistence and organization of human ECs
      in vitro will likely be required for their participation in vascularization of
      CSS + ECs after grafting.

PMID- 15247833
TI  - Use of free serratus anterior muscle slips for the reconstruction of dorsal-side
      defects of the hand resulting from hot press injury.
AB  - Mutilation of the hand as a result of hot press injury, the common
      characteristics of which are extensive soft tissue and extensor tendon loss,
      metacarpal and phalangeal necrosis, exposition of multiple joints, and infection,
      presents a serious challenge to the hand surgeon. Free transfer of the inferior
      three slips of the serratus anterior muscle is a useful surgical option for the
      reconstruction of dorsal-side defects in the hand. The versatility of the three
      separate slips, which are easily divisible for contouring, enables individual
      reconstruction of the different digits. Long vascular pedicle, low donor-site
      morbidity, and durability are other advantages. Four male patients with hot press
      injury of the dorsal side of the hand were treated with free transfer of serratus
      anterior muscle slips and split-thickness skin grafts. Follow-up period ranged
      between 5 and 12 years. Late functional and cosmetic results are presented.

PMID- 15247834
TI  - Assessing the relationship between locus of control and social competence in
      pediatric burn survivors attending summer cAMP.
AB  - Previous research suggests that children with burn injuries often exhibit
      psychological and social difficulties. The areas of functioning that are affected
      most often include level of anxiety, social competence, and self-esteem. Those
      children having an internal locus of control (LOC) have been shown to react more
      positively to physical disorders and to have better psychological responding in
      nonburn populations. The purpose of this study was to determine whether there is
      a relationship between LOC and social competence in pediatric burn survivors.
      Participants were children aged 8 to 18 years who had been treated for a burn
      injury and attended a 1-week summer camp for pediatric burn survivors. Results
      indicated that the type of LOC was not a predictor of the overall level of social
      competence, as reported on three different measures of social competence.
      However, LOC significantly accounted for variability in the child's cooperation
      level, according to parent report. Other results are discussed, as well as
      implications for future research and clinical work in this area.

PMID- 15247835
TI  - Analysis of burn injuries in frontal automobile crashes.
AB  - The purpose of this study was to investigate burn injuries resulting from frontal
      automobile crashes and to determine the effects of frontal airbags on the
      incidence of burn injuries. The study included 25,464 individual cases from the
      National Automotive Sampling System database files for the years 1993 to 2000.
      Occupants were at a significantly higher risk to sustain a burn injury when
      exposed to an airbag deployment (1.54%) compared with those who received a burn
      injury when not exposed to an airbag deployment (0.02%; P = 0.02). In contrast to
      previous publications, this study found that 1.53% of front seat occupants
      exposed to an airbag deployment sustained an airbag-induced burn injury. The vast
      majority of airbag-induced burn injuries were minor (98.7%); however, in cases
      with no airbag deployment, the burns were often much more serious, including
      fatal burns (29.6%). Occupant weight, height, sex, seatbelt use, and seat
      position were all found not to be significant in predicting the risk of airbag
      induced burn injury, whereas age and crash velocity were found to be significant.

PMID- 15247836
TI  - Early-onset unilateral electric cataract: a rare clinical entity.
AB  - Electrical injury may result in cataracts, which usually occur bilaterally. In
      this report, we present a rare complication of such an injury presenting as a
      unilateral cataract in a 33-year-old woman with a painless but gradual worsening
      of vision in her left eye 3 weeks after sustaining a high-voltage electrical
      injury. A cataract did not develop in the right eye during 26 months of follow
      up. The patient underwent successful cataract surgery with an excellent return of
      vision. Electrical injuries may result in the formation of a unilateral cataract
      and therefore an ophthalmic examination should be performed regularly in the
      early recovery period of such injuries. Cataract surgery with intraocular lens
      implantation results in an excellent return of vision in patients with electrical
      cataract who do not have any other ocular damage.

PMID- 15247837
TI  - A history of the development of muscle perforator flaps and their specific use in
      burn reconstruction.
AB  - Only rarely does coverage in the burn patient require the use of a vascularized
      flap. However, when mandatory, a knowledge of all alternatives is essential
      because common donor sites may have been badly burned and unavailable. The recent
      development of the muscle perforator flap may prove to be another valuable
      option. These flaps are nourished by the familiar musculocutaneous perforators
      but differ in that their complete intramuscular dissection is required during
      flap elevation so that no muscle need be included with the flap. A review of six
      cases using muscle perforator free flaps specifically for burn reconstruction or
      rehabilitation demonstrates how the same large cutaneous territory of a
      musculocutaneous flap can still be captured while the muscle and therefore its
      function is preserved.

PMID- 15247839
TI  - Causes and treatment of burns from grease.
AB  - A large number of burns are sustained every year as the result of kitchen grease.
      A review of a 13-month period at the Joseph M. Still Burn Center in Augusta,
      Georgia, revealed 60 cases (9.4% of acute burn admissions). Forty-five (75%) of
      these patients were adults and 25% were children. There were 23 females and 37
      males. Forty-two percent of the adults and 33% of the children had some
      percentage of third-degree injury. The average total body surface area burn in
      adults was 5.9% and in children 6.3%. There were no deaths in this series. Burns
      usually occurred as the result of scalds with grease while cooking. Spilling
      grease on children in the kitchen was a frequent problem. Burns due to ignition
      of grease was also a cause of injury. Most of the injuries were potentially
      preventable, and therefore the importance of burn appropriate safety programs is
      stressed.

PMID- 15247840
TI  - Buses as fire hazards: a Swedish problem only? Suggestions for fire-prevention
      measures.
AB  - In Sweden, approximately 6% of all human transportation is made via buses. The
      Swedish Board of Accident Investigation and the Swedish Rescue Services Agency
      have pointed out repeatedly that buses are potential fire and burn hazards, not
      only when involved in collisions but also in other circumstances. The number of
      fire incidents is increasing, especially in newer buses. In conjunction with the
      Swedish Rescue Services Agency, we examined some of the recent bus fires in
      Sweden. We did not find any casualties, but the results of our study suggest that
      casualties as a result of bus fires are imminent unless preventive measures are
      taken. We also studied experiences from previous bus fires and suggest preventive
      measures.

PMID- 15247841
TI  - Saturday-morning television: do sponsors promote high-risk behavior for burn
      injury?
AB  - Television has become an important tool for learning and socialization in
      children. Although television violence has been associated with adverse effects,
      data on depiction of fire and burn injury are lacking. We sought to determine
      whether Saturday-morning television programming, viewed primarily by children,
      depicts fire and burn injury as safe or without consequence, thus potentially
      increasing the incidence of burn injury in children. This was a prospective
      observational study. Saturday-morning children's television programs were
      videotaped from 7 AM to 11 AM for eight different television networks during a 6
      month period. Tapes were scored for scenes depicting fire or smoke by independent
      observers. Recorded items included show category, scene type, gender target,
      context of fire, and outcome after exposure to flame. Fire events were documented
      during programs and their associated commercials. A total of 108 hours of
      children's programs, 16 hours per network, were recorded. Scenes depicting fire
      or smoke were identified 1960 times, with 39% of events occurring during the
      program itself and 61% in commercials. Fire was depicted as either safe or
      without consequence in 64% of incidents. Action adventure stories accounted for
      56% of flame depictions. Overall, one incident involving flame and fire was
      portrayed for each 3 minutes of television programming. Saturday-morning
      television programming frequently depicts fire as safe, empowering, or exciting.
      The incidence of flame use in programming varies between stations but is most
      prevalent in action/adventure stories. Television commercials, although brief,
      provide the majority of the misinformation regarding fire. Medical professional
      societies should alert the public to this potential hazard and recommend
      responsible portrayal of fire in children's television programming.

PMID- 15247842
TI  - Identifying environmental factors that influence the outcomes of people with
      traumatic brain injury.
AB  - OBJECTIVES: To determine the types of environmental barriers reported by persons
      with traumatic brain injury (TBI) and to identify the relations between
      environmental barriers and such components of societal participation as
      employment, community mobility, social integration, and life satisfaction.
      DESIGN: Seventy-three persons with TBI who were participating in the TBI Model
      Systems program at Craig Hospital were surveyed at 1 year, using a new measure of
      the environment, the Craig Hospital Inventory of Environmental Factors (CHIEF),
      which rates frequency and impact of 25 barriers. RESULTS: Transportation, the
      surroundings, government policies, attitudes, and the natural environment were
      the environmental barriers with the greatest reported impact. Those who were
      married, older, and unemployed or not in school reported the most barriers
      overall. Additionally, those reporting a greater impact from environmental
      barriers also reported lower levels of participation and life satisfaction.
      CONCLUSIONS: Although environmental barriers affect TBI survivors and play a role
      in their outcomes, their interplay with other, perhaps as yet unidentified,
      factors requires continued research. CHIEF may be a valuable tool for
      understanding the environment's role in the lives of people with TBI, and
      identifying the general environmental domains where interventions are needed to
      reduce their negative impact.

PMID- 15247843
TI  - Perceived needs following traumatic brain injury.
AB  - OBJECTIVES: (1) Provide population-based estimates of perceived needs following
      traumatic brain injury (TBI) and the prevalence of unmet needs 1 year postinjury;
      (2) identify relations among needs that define unique clusters of individuals;
      and (3) identify risk factors for experiencing selected needs. DESIGN: Telephone
      survey 1 year after injury of a prospective cohort of all people hospitalized
      with TBI in the state of Colorado during 2000. MEASURES: Self-reported need for
      assistance in 13 areas of functioning. RESULTS: A total of 58.8% of persons
      hospitalized with TBI experienced at least 1 need during the year following
      injury; 40.2% will experience at least 1 unmet need 1 year after injury. Most
      frequently experienced needs were "improving your memory, solving problems
      better" (34.1%), "managing stress, emotional upsets" (27.9%), and "managing your
      money, paying bills" (23.3%). Cluster analysis revealed 8 distinctive groupings
      of subjects. If a need existed, those least likely to be met involved cognitive
      abilities, employment, and alcohol and/or drug use. CONCLUSIONS: Results were
      consistent with findings from previous assessments of need for services based on
      surveys of convenience samples; however, the prevalence of unmet needs 1 year
      after injury may be higher than previously suspected. More post-hospital services
      addressing cognitive and emotional problems appear needed. Risk factors for
      experiencing needs suggest potential avenues for clinical intervention.

PMID- 15247844
TI  - Severity of injury and service utilization following traumatic brain injury: the
      first 3 months.
AB  - OBJECTIVE: To describe the medical and rehabilitation service use of model
      systems by brain injured participants 1 to 3 months postdischarge from inpatient
      rehabilitation. DESIGN: Prospective follow-up study. SETTING: Georgia Model Brain
      Injury System (GAMBIS). PARTICIPANTS: Seventy-three GAMBIS subjects consenting to
      participate in the utilization substudy. MAIN OUTCOME MEASURES: Receipt of
      services and intensity of service use. ANALYSIS: Chi-square analysis of receipt
      of services by severity of injury. RESULTS: The likelihood of service use did not
      vary with severity of injury. Data suggest that intensity of service use was a
      function of injury severity. CONCLUSIONS: Subjects with mild and moderate
      injuries were as likely to use a range of medical and rehabilitation services
      during the 3-month postdischarge period as those with severe injuries.
      Traditional rehabilitation services, such as physical therapy, were far more
      likely to be used, than nontraditional services, such as psychological
      counseling, in spite of the high level of cognitive and social disability
      associated with traumatic brain injury.

PMID- 15247845
TI  - Clinical characteristics of acute dysphagia in pediatric patients following
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To document the clinical characteristics of acute dysphagia in
      a group of pediatric patients after traumatic brain injury (TBI). RESEARCH
      DESIGN: Prospective group study. METHODS: Fourteen subjects (7 males, 7 females),
      aged 4 years 1 month to 15 years, with moderate or severe TBI (Glasgow Coma Scale
      [GCS] < 12). Subjects were assessed via clinical bedside examination documenting
      cognitive status, oromotor function, feeding function, dietary recommendations,
      and an indication of overall feeding severity. RESULTS: A pattern of impaired
      cognition, altered behavior related to feeding, severe tonal and postural
      deficits, oromotor, respiratory, and laryngeal impairments, and oral sensitivity
      issues was revealed. CONCLUSIONS: Swallowing impairment was affected by
      multilevel deficits, which both individually and in combination had a negative
      impact on swallowing competence and safety. In light of deficits identified,
      which could not be observed on videofluoroscopic investigation alone, this study
      highlighted the importance of the clinical bedside examination in assessing
      dysphagia in pediatric patients post-TBI for identifying targets for
      intervention.

PMID- 15247846
TI  - An evaluation of continuous positive airway pressure (CPAP) therapy in the
      treatment of hypernasality following traumatic brain injury: a report of 3 cases.
AB  - OBJECTIVE: To evaluate the effectiveness of continuous positive airway pressure
      (CPAP) therapy in the treatment of hypernasality following traumatic brain injury
      (TBI). DESIGN: An A-B-A experimental research design. Assessments were conducted
      prior to commencement of the program, midway, immediately posttreatment, and 1
      month after completion of the CPAP therapy program. PARTICIPANTS: Three adults
      with dysarthria and moderate to severe hypernasality subsequent to TBI. OUTCOME
      MEASURES: Perceptual evaluation using the Frenchay Dysarthria Assessment, the
      Assessment of Intelligibility of Dysarthric Speech, and a speech sample analysis,
      and instrumental evaluation using the Nasometer. RESULTS: Between assessment
      periods, varying degrees of improvement in hypernasality and sentence
      intelligibility were noted. At the 1-month post-CPAP assessment, all 3
      participants demonstrated reduced nasalance values, and 2 exhibited increased
      sentence intelligibility. CONCLUSIONS: CPAP may be a valuable treatment of
      impaired velopharyngeal function in the TBI population.

PMID- 15247847
TI  - Rehabilitative management of patients with disorders of consciousness: grand
      rounds.
AB  - BACKGROUND: There are no standards of care to guide the selection of
      rehabilitation assessment and treatment procedures for patients with disorders of
      consciousness. Recently, consensus-based recommendations for management of
      patients in the vegetative and minimally conscious states have been developed and
      disseminated in neurology and neurorehabilitation. This is an important first
      step toward achieving evidence-based guidelines of care. OBJECTIVE: Using a
      "Grand Rounds" format, we illustrate the application of consensus-based
      diagnostic, prognostic, and treatment recommendations in a patient who sustained
      severe traumatic brain injury with prolonged alteration in consciousness. After
      discussing the salient features of the case, we summarize the basic tenets of
      clinical care for this population.

PMID- 15247848
TI  - Collaboration between cognitive science and cognitive rehabilitation: a call for
      action.
AB  - The fields of cognitive science and cognitive rehabilitation share a fundamental
      interest in the nature of cognition. Both groups address questions that are
      critical to our understanding of human thought. Researchers in basic cognitive
      science address these questions from a theoretical perspective. Clinicians in
      cognitive rehabilitation address them from an applied perspective for individuals
      with brain injuries. Collaborative efforts and cross-fertilization of theory and
      practice have been less than what might be expected given the underlying
      commonality of the two fields. Here, we explore the complex nature of the
      relationship between cognitive rehabilitation and cognitive science, discuss
      barriers to collaboration, and suggest ways of overcoming those barriers.

PMID- 15247849
TI  - Determination of effort level, exaggeration, and malingering in neurocognitive
      assessment.
AB  - OBJECTIVES: This article presents a review of the field of effort level
      determination in TBI assessment as well as how to determine which effort level
      measure is most appropriate for common assessment situations. The importance of
      effort level assessment in forensic settings, and also in assessments conducted
      in both diagnostic and rehabilitation programs, which rely on test performances
      to develop treatment plans or to measure progress and outcome, is discussed.
      METHODS: Historical review and summaries of specific measures designed to
      characterize effort level in assessment of persons suffering TBI. RESULTS: There
      are several effort level measures that have withstood the scrutiny of cross
      validation research. These include the Computerized Assessment of Response Bias
      (CARB), Portland Digit Recognition Test (PDRT), Test of Memory Malingering
      (TOMM), Validity Indicator Profile (VIP), Victoria Symptom Validity Test (VSVT),
      and Word Memory Test (WMT). CONCLUSIONS: Depending on the neurocognitive test
      performances(s) evidencing suboptimal effort or complaints that may be
      questionable, it is recommended that at least 2 of the above-listed measures be
      employed for proper assessment of effort level.

PMID- 15247851
TI  - [Is it reasonable to risk the long-term side effects of immunosuppressive
      treatment in chronic neurological diseases?].

PMID- 15247852
TI  - [Cannabis and cannabinoid receptors: from pathophysiology to therapeutic
      options].
AB  - BACKGROUND: Although cannabis has been used as a medicine for several centuries,
      the therapeutic properties of cannabis preparations (essentially haschich and
      marijuana) make them far most popular as a recreational drugs. STATE OF THE ART:
      Scientific studies on the effects of cannabis were advanced considerably by the
      identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized
      as the major active constituent of cannabis. Cloning of the centrally located CB1
      receptor in 1990 and the identification of the first endogenous ligand of the CB1
      receptor, anandamide, in 1992 further advanced our knowledge. PERSPECTIVE AND
      CONCLUSIONS: Progress has incited further research on the biochemistry and
      pharmacology of the cannabinoids in numerous diseases of the central nervous
      system. In the laboratory animal, cannabinoids have demonstrated potential in
      motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and
      neuroprotector agents. Several clinical studies are currently in progress, but
      therapeutic use of cannabinoids in humans couls be hindered by undesirable
      effects, particularly psychotropic effects. CB1 receptor antagonists also have
      interesting therapeutic potential.

PMID- 15247853
TI  - [Astrocytic cytochromes p450: an enzyme subfamily critical for brain metabolism
      and neuroprotection].
AB  - INTRODUCTION: Astrocytes are involved in multiple brain functions in
      physiological conditions. Cytochromes P450 are expressed in astrocytes and play a
      role in brain metabolism and in neuroprotection. BACKGROUND: Although the levels
      of various cytochromes P450 in brain regions are low, these enzymes were reported
      to be expressed at relatively high level in astroglial cells and may play a
      critical role in the biotransformation of endogenous or exogenous compounds.
      Astroglial cytochromes P450 expression suggests a putative capacity to metabolize
      psychoactive or lipophilic xenobiotics in situ, associated with pharmacological
      and/or toxicological consequences. Astrocytes appear to be the most active
      steroidogenic cells in the brain, expressing neurosteroidogenic cytochromes P450
      and producing various neurosteroids. Cytochrome P450 epoxygenase enzymes, which
      catalyze the formation of vasoactive compounds are also present in astrocytes,
      contributing to the regulation of the cerebral blood flow. PERSPECTIVES AND
      CONCLUSION: This review underlines the crucial roles of astroglial cytochromes
      P450 in brain functions. Identification of the molecular mechanisms involved in
      the regulation of these enzymes could open therapeutic perspectives and improve
      our understanding in neuroprotection.

PMID- 15247854
TI  - [Treatment of progressive multiple sclerosis with monthly pulsed cyclophosphamide
      methylprednisolone: predictive factors of treatment response].
AB  - INTRODUCTION: Cyclophospamide is used in the treatment of progressive multiple
      sclerosis. We were looking for predictive indicators of treatment response.
      MATERIAL AND METHODS: Forty-seven patients with secondary progressive multiple
      sclerosis and seven others with primary progressive received monthly infusions of
      cyclophosphamide (750mg/m2) and methylprednisolone (500mg). During the year
      before cyclophosphamide the EDSS had worsened one point in all patients with or
      without surimposed relapses. Evaluation was based on EDSS change at 6, 12, 24
      months and 5 years. RESULTS: Among secondary progressive patients, 91 per 100
      (43/47) were stable or improved at 12 months, 65 per 100 (26/40) at 24 months and
      22 per 100 (5/23) at 5 years. Annual relapse rate decreased from 0.81 before
      treatment to 0.48 during treatment and 0.12 after treatment (p<0.001). At 24
      months, efficacy was correlated to a progressive phase lasting less than 5 years
      (p<0.01) and to a rapid increase of EDSS of at least 2 points the year before
      treatment (p<0.05). There were no influences of age, EDSS and surimposed relapses
      at the beginning of treatment, and other immunoactive drugs administrated before
      cyclophosphamide. There was no significant difference in quality of response to
      treatment between patients with primary progressive and secondary progressive
      multiple sclerosis. CONCLUSION: Cyclophosphamide appears to be more efficient in
      early stage of progressive multiple sclerosis independently of age, relapses or
      neurological disability scale.

PMID- 15247855
TI  - [Communication disorders after decline in sub-cortical aphasia: the role of
      fronto-sub-cortical disconnection?].
AB  - INTRODUCTION: Pragmatic analysis of Language difficulties examines the pertinence
      and adaptation of the spoken Language which can be disturbed even when
      phonologic, syntactic and semantic functions, taken separately, appear normal.
      Disorders of pragmatic Language function remain poorly explored and the few
      published papers in adult neuropsychology have been devoted to patients with
      traumatic frontal lesions. METHODS: In the present study we report the case of a
      patient admitted for right hemiplegia with "dissident" aphasia related to a
      capsulo-lenticular hematoma. Aphasic disorders progressively improved but with
      the occurrence of speech disorders which were assessed by pragmatic indices.
      RESULTS: There was no difference between free and directed interview with the
      exception for the non-contingencies which were significantly more frequent in the
      directed interview. As compared with the spoken Language of a normal individual,
      highly significant differences were noted for incoherent lexical proximities, non
      contingencies and markers of difficulty. DISCUSSION: and conclusion. For some
      Authors, the pragmatic speech disorders observed in this patient during the
      directed interview are linked to abnormal executive functions, also noted in the
      patient. The difficulties to adjust to speech constraints of the interview
      context could be related to a fronto-subcortical disconnection resulting in this
      patient to the left capsulo-lenticular lesion.

PMID- 15247856
TI  - [Spontaneous muscular haematomas in hemiplegic patients receiving anticoagulation
      therapy].
AB  - INTRODUCTION: Muscular hematomas are frequently reported as a complication of
      anticoagulation therapy. METHODS: We report six cases of spontaneous muscular
      hematomas occurring in hemiplegic patients receiving anticoagulation therapy
      using heparin, low-molecular-weight heparin or fluindione. Anticoagulation
      therapy was given in prophylactic doses to two patients to prevent deep vein
      thrombosis and in therapeutic doses to four patients with deep vein thrombosis,
      pulmonary embolism or cardiac arrhythmia. Two patients experienced episodes of
      bleeding when heparin and fluindione were temporarily associated. RESULT:
      Contrary to previous reports, the more frequent site of bleeding was not the ilio
      psoas muscle (only 2 patients); hematomas were also observed in hip adductors and
      gluteus muscles. The most striking finding was the constant location of the
      hematoma on the hemiplegic side. CONCLUSION: Location on the hemiplegic side can
      lead to underestimating the frequency of neurologic compression by the hematoma;
      the diagnosis can nevertheless be established by electromyography. Local signs
      may not be present, but general signs of hypovolemia and anemia are more
      frequent. Ultrasound may be the first line investigation but in our experience,
      the results can be misleading and computed tomography (CT) or MRI are often
      required to confirm the diagnosis.

PMID- 15247857
TI  - [Intracranial extension of extracranial vertebral artery dissections. A review of
      16 cases].
AB  - INTRODUCTION: Vertebral artery (VA) dissections can involve both the extracranial
      and intracranial portions of the VA. Intradural extension explains the occurrence
      of subarachnoid hemorrage (SAH). We have studied the rate of this extension, the
      risk of associated SAH and the therapeutic repercussions at the acute stage.
      METHODS: From 1985 to 2001, 42 patients with a recent extracranial VA dissection
      were admitted to our department of neurology. When the diagnosis of extracranial
      VA dissection (involving the first, second or third segment of the VA) was
      established, we looked for an ipsilateral intracranial extension (involving the
      fourth segment of the VA and/or the basilar artery). VA dissections strictly
      located at the intracranial level were excluded. RESULTS: Among 42 patients with
      angiographically diagnosed extracranial VA dissections, 16 patients (38 percent)
      had an ipsilateral intradural extension. Two of them developed an inaugural and
      spontaneous SAH. After a mean follow-up of 4 Months under antithrombotic
      treatment, none of the patients has developed SAH or recurrent SAH. CONCLUSIONS:
      Because of the potential risk for spontaneous SAH at the acute stage, it seems
      important to exclude an intracranial extension. Lumbar puncture should be
      undertaken to exclude SAH before consideration of antithrombotic therapy.

PMID- 15247858
TI  - [The presentation of small-cell lung cancer with metastatic carcinomatous
      encephalitis in a non-Hodgkin's lymphoma patient].
AB  - BACKGROUND: Carcinomatous encephalitis or milary cerebral metastases
      characterized by signs of diffuse encephalopathy is a rare form of brain
      metastases. Tiny tumor nodules are seen throughout the cortical and subcortical
      gray matter. OBSERVATION: We report the case of a patient with a history of non
      Hodgkin lymphoma who developed carcinomatous encephalitis probably secondary to
      small-cell lung cancer. This case is discussed in light of findings of 16 cases
      of carcinomatous encephalitis reported in the literature. We discuss clinical,
      radiological, histological, pathophysiological characteristics and the survival
      of this form. CONCLUSION: The frequency of carcinomatous encephalitis is
      underestimated because clinical expression is non specific. Brain magnetic
      resonance imaging must be performed in all patients presenting encephalopathy
      without an obvious cause.

PMID- 15247859
TI  - [Recurrent catamenial encephalopathy secondary to toxic shock syndrome].
AB  - INTRODUCTION: Neurological clinical manifestations are often observed in toxic
      shock syndromes. However they unusually dominate the clinical picture.
      OBSERVATION: We present a case of recurrent catamenial encephalopathy, with
      epileptic seizures, revealing a menses toxic shock syndrome.

PMID- 15247860
TI  - [Bupropion-induced epileptic seizures].
AB  - INTRODUCTION: Bupropion hydrochloride (Zyban) is prescribed for smoking
      cessation. It is contraindicated in patients with seizure disorders. We report
      three patients with generalized tonic-clonic seizure that occurred a few days
      after the intake of this drug. OBSERVATIONS: The first two patients had no
      personal or family seizure history. They had generalized tonic-clonic seizure
      after taking bupropion (300 mg per day) for a few days. Acute symptomatic
      seizures were diagnosed in both cases. The third patient suffered from myoclonic
      jerks during adolescence, had a history of seizure after high dose codeine
      treatment and a family seizure history. She had generalized tonic-clonic seizure
      after taking bupropion 300 mg per day. EEG showed paroxystic generalized activity
      and photosensitivity, consistent with the diagnosis of juvenile myoclonic
      epilepsy. DISCUSSION: Bupropion can lower seizure threshold. The incidence of
      seizure at 300 mg per day is 1/1000 patients treated. CONCLUSION: Many commonly
      prescribed drugs can trigger epileptic seizure, bupropion is one of them. When
      prescribing this drug, this adverse effect must be acknowledged and health
      practitioners should be aware of this risk.

PMID- 15247861
TI  - [Encephalopathy and acute renal failure during acyclovir treatment].
AB  - INTRODUCTION: Adverse neurological and renal effects can occur in patients taking
      acyclovir. Neurotoxicity of acyclovir results from an accumulation of the
      antiviral and its metabolites in the bloodstream. This can be observed in the
      elderly or in patients with chronic renal failure, generally in dialysis
      patients. Acute renal failure results from intratubular crystallization of
      acyclovir. OBSERVATION: A 78-year-old right-handed woman was admitted in an
      emergency setting for aphasia. Analysis of the cerebrospinal fluid was normal,
      but herpetic meningo-encephalitis was suspected and intravenous treatment was
      initiated with acyclovir. After the second infusion, the patient began to suffer
      from visual hallucinations, confusion and acute renal failure. Herpes PCR was
      negative in the cerebrospinal fluid, and the adverse drug reactions regressed
      completely after 72 hours. CONCLUSION: Renal function has to be checked often in
      patients given acyclovir for appropriate dose titration. Patients recover prompt
      from the adverse effects at drug withdrawal.

PMID- 15247862
TI  - [A surgical approach to Holmes' tremor associated with high-frequency synchronous
      bursts].
AB  - INTRODUCTION: The effectiveness of thalamic stimulation is now clearly
      demonstrated for essential tremor, but remains to be demonstrated for other types
      of tremor. OBSERVATION: A young woman presented Holmes' tremor resulting from a
      pontine tegmental hemorrhage related to an arteriovenous malformation. A surgical
      approach was considered when major functional impairment persisted at 2-year
      follow-up despite drug therapy. The patient underwent unilateral thalamic deep
      brain stimulation (Vim); major improvement persisted at eighteen months follow
      up. CONCLUSION: This observation is in line with previous reports suggesting that
      thalamic surgery can be one of the best options for treating medically
      intractable Holmes' tremor. The mechanism underlying the tremor, implying dentate
      rubro-thalamic pathways is discussed. Moreover, the patient exhibited short
      periods of 16Hz tremor when her arms were maintained outstretched. Thalamic
      stimulation also appears to be effective for these high-frequency synchronous
      cerebellar bursts.

PMID- 15247863
TI  - [Intra-cavernous aneurysm of the internal carotid artery complicating sphenoid
      sinusitis].
AB  - INTRODUCTION: Mycotic or post-infectious aneurysm of the intra-cavernous portion
      of the internal carotid artery is uncommon. CASE REPORT: We report here the case
      of a patient who developed progressive left ophthalmoplegia, with left hemi
      crania three weeks after a tooth extraction. The patient was febrile.
      Neuroradiological and microbiological analysis led to the diagnosis of sphenoidal
      and ethmoidal sinus infection with extension to the left cavernous sinus. An
      aneurysm of the intra-cavernous portion of the left internal carotid artery was
      also found. CONCLUSIONS: The risk of rupture for this kind of aneurysm is
      difficult to assess. Treatment always consists in prolonged and adapted
      antibiotic therapy. For certain patients neurosurgical or endovascular repair is
      necessary. We followed our patient for four Years without surgical intervention.
      The diameter of the aneurysm has remained stable.

PMID- 15247864
TI  - [Demyelinating neuropathy and Sjogren's syndrome: a diagnostic pitfall].
AB  - INTRODUCTION: Neuropathies induced by Sjogren's syndrome (SS) are usually axonal.
      Nevertheless some demyelinating neuropathies have been described in patients with
      SS. To date, the relationship between demyelinating neuropathies and SS remains
      imprecise. CASE REPORT: A 75 year-old man presented with a chronic history of
      sensory disturbances linked to demyelinating neuropathy. Electroneuromyography
      revealed a demyelinating neuropathy and complementary tests revealed both
      Sjogren's syndrome (SS) and HMSN IA. CONCLUSION: We suggested that an inherited
      affection might be researched before considering that demyelinating neuropathy
      might be a form of peripheral nervous system involvement in SS.

PMID- 15247865
TI  - [Thoughts on the definition of postherpetic pain: the time criterion adds
      nothing].
AB  - In postherpetic neuralgia, as in all types of neuropathic pain, it is generally
      accepted that outcome can be affected early management with specific analgesics.
      However, when one looks at the diagnostic criteria appearing in the literature,
      there is no consensus. Authors use the notion of latency to situate the onset of
      postherpetic neuralgia within the continuum of herpetic pain. Depending on the
      Author, this latency period ranges from one to six Months after the skin
      eruption. This latency is poorly compatible with early intervention and not well
      adapted to everyday practice. With the aim of finding ways to improve the
      management of pain, the Neuropathic Pain Expert Group agreed upon a new
      definition. Postherpetic neuralgia is pain in the involved site after the skin
      eruption has healed and which displays the features of neuropathic pain. This
      definition, which does away with the latency criterion, is based on the
      identification of one or more clinical features of neuropathic pain in a
      situation of treatment failure, namely: presence of chronic unsolicited pain
      (burning, tightness, pressure) and/or paroxysmal pain (tingling, stabbing pain)
      and/or mechanical hyperalgia/allodynia (to friction or pressure) and/or
      temperature sensitivity (to heat and/or cold). Such pain occurs in circumscribed
      neurologic zones in which a sensory deficit can be demonstrated and is usually
      associated with dysesthesia and/or paresthesia.

PMID- 15247866
TI  - [What is the remaining role of heparin in the treatment of acute cerebral
      ischemia?].

PMID- 15247867
TI  - [Lumbar epidural lipomatosis].

PMID- 15247868
TI  - [Management of restless legs and periodic movements of sleep].
AB  - INTRODUCTION: Restless legs syndrome and periodic leg movements in sleep are
      frequently observed, often in association. Misdiagnosis of these two conditions
      is common. STATE OF ART: Physical examination can provide the diagnosis of
      restless legs syndrome but polysomnography recording must be performed to confirm
      the presence of periodic leg movements. Dopaminergic pathways are implicated in
      the pathophysiology of these two syndromes and the same treatment is given:
      dopaminergic agents, benzodiazepines, opioids and/or antiepileptic drugs.
      PERSPECTIVES AND CONCLUSION: Treatment provides an improvement in quality-of-life
      for these patients.

PMID- 15247870
TI  - [Is there a link between the food-cobalamin malabsorption and the pernicious
      anemia?].
AB  - BACKGROUND: A relation between food-cobalamin malabsorption and pernicious anemia
      has been suggested, particularly in the event of food-cobalamin malabsorption
      related to hypochlorhydric atrophic gastritis. STUDY DESIGN: This work describes
      three cases of well-documented cobalamin deficiency related to food-cobalamin
      malabsorption in three women aged 56, 82 and 68 Years who had atrophic gastritis
      (not associated with Helicobacter pylori infection) and later developed authentic
      pernicious anemia. CONCLUSIONS: This work illustrates the potential relation
      between these two disorders responsible for cobalamin deficiency.

PMID- 15247871
TI  - [Graves' disease and hyperprolactinemia in a patient with Noonan syndrome
      neurofibromatosis type 1].
AB  - We report the case of a 42-Year-old woman with Recklinghausen disease
      (neurofibromatosis type 1) and Noonan syndrome who developed Graves' disease.
      Hyperthyroidism, which had existed for two Years without treatment, led to the
      discovery of neurofibromatosis type 1. The diagnosis of Graves' disease was
      confirmed by blood hormone levels, thyroid gland ultrasound, radioisotope scan
      and thyroid iodine uptake. Additional tests were carried out due to the patient's
      short stature and the presence of subcutaneous nodules. Hyperprolactinemia, bone
      defects (bone density testing), and abnormal MRI signals from the optic chiasma
      were disclosed. The diagnosis of Recklinghausen disease was proven
      histologically. The possible co-existence of neurofibromatosis type 1 and Noonan
      syndrome are discussed on the basis of this clinical case.

PMID- 15247872
TI  - [Severe neonatal hyperthyroidism which reveals a maternal Graves' disease].
AB  - Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis
      is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or
      fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.).
      Due to transfer into the fetal compartment of maternal antibodies which stimulate
      the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1%
      of children born to these mothers are described as having hyperthyroidism.
      Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies;
      clinical signs usually disappear during the first four Months of life. The most
      frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter,
      hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid
      retraction. Diagnosis is based on determination of the blood level of
      triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of
      hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The
      kinetics of TSI provides a guide for therapeutic adaptation and disappearance of
      TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism
      have been shown to be caused by germline mutation of the thyrotropin receptor. We
      report a case of severe neonatal hyperthyroidism which led to the diagnosis of
      maternal Graves' disease.

PMID- 15247873
TI  - [Prevalence of celiac disease markers in a French cohort of children and
      adolescents with type 1 diabete mellitus].
AB  - The aim of this study was to determine the prevalence of celiac disease (CD)
      markers in a French cohort of 84 children type 1 diabetics. Detection of
      antitransglutaminase (AtTG), antiendomysium (AEA) and antigliadin (AGA)
      antibodies was performed. Group 1 included 81 (96.4%) diabetic patients with
      negative antibodies. Group 2 included 3 patients (3.6%) with positive serological
      markers: 1 AGA-AEA-AtTG and 1 AEA-AtTG with proved histological diagnosis and 1
      AGA positive with negative histology. No statistically significant difference was
      observed between the groups with regard to age, duration of diabetes, familial
      target stature, and ratios Height/Age and Weight/Height. Presence of CD
      serological markers was related to a lower level of HbA1c. Prevalence of CD
      serological markers is important in this French cohort but lower than other
      countries.

PMID- 15247874
TI  - [Pioglitazone insulin sensitivity and type 2 diabetes mellitus: recent data].
AB  - Thiazolidinediones ("glitazones") were recently added to the oral treatment of
      type 2 diabetes. Two glitazones are available in France, pioglitazone and
      rosiglitazone, which progressively were granted broader therapeutic indications
      since their launch in 2002. This review presents the most recent pioglitazone
      pharmacological and clinical data, with a particular emphasis on the QUARTET
      clinical study program results. Available information generates perspectives and
      hopes: prevention of the progressive decline in beta-pancreatic cell function
      (and possibly, prevention of type 2 diabetes in at-risk subjects), cardiovascular
      prevention in type 2 diabetic patients depending on the results of the ongoing
      prospective morbi-mortality studies in high risk type 2 diabetic patients.

PMID- 15247876
TI  - [The heart and androgens].
AB  - Beyond regulation of sexual function, male steroids play an important role in
      many physiological homeostasis systems, including the cardiovascular system. Via
      a specific androgen receptor, testosterone mediates cardiomyocyte trophicity both
      in physiological situations and in hypertrophy-related cardiac diseases.
      Androgens also regulate pathological levels of inflammatory cytokines such as Il
      6 or TNF in advanced heart failure. They also mediate vascular resistance since
      coronary vasodilatation has been proven both in vitro and in vivo. Reduced free
      testosterone serum levels (age-mediated or premature coronary artery disease)
      promote a pro-atherogenic lipid profile expressed as lower serum HDL-cholesterol
      and up-regulation of triglyceride levels. This observation has relevant clinical
      implications for the evaluation and treatment of coronary artery disease. As most
      of normal and diseased cardiovascular system functions are influenced by
      androgens, further evaluation of their physiological implications should be
      undertaken as well as large-scale rigorous studies of the therapeutic
      implications in two disabling diseases, coronary heart disease and heart failure.

PMID- 15247875
TI  - [Genetically-driven or supposed genetic-related insulinomas in adults: validation
      of the surgical strategy proposed by the A.F.C.E./G.E.N.E.M].
AB  - Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the
      Department of General and Endocrine Surgery of the Lille University Hospitals.
      The present report deals with 13 patients with proven multiple endocrine
      neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity
      differs from spontaneous insulinoma by the presence of multiple foci in the
      pancreas. Enucleation is not advised in this setting due to the strong likelihood
      of persistence or recurrence. Various studies suggest different strategies for
      preoperative localization and surgical approach. We analyzed retrospectively the
      surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this
      study was to validate the strategy, integrate the contribution of genotypic
      diagnosis, simplify preoperative imaging studies, and re-evaluate the value of
      intraoperative baseline secretin-stimulated insulin measurements. We recommend
      preoperative endoscopic ultrasonography of the pancreatic head only and routine
      left pancreatectomy with enucleation of cephalic tumors under intraoperative
      hormone monitoring. Preoperative invasive localization studies are proposed only
      if the endoscopic ultrasonography is negative for the pancreatic head.
      Intraoperative secretin stimulation test can be useful in difficult cases,
      especially with concurrent nesidioblastosis or in case of secondary surgery. All
      but one of the 13 patients achieved long-term cure with this strategy.

PMID- 15247877
TI  - [Nephrolithiasis and primary hyperarathyroidism in pregnancy].
AB  - Diagnosis of hyperparathyroidism is unusual during pregnancy. The presence of a
      renal stone is a very exceptional finding. Hypercalcemia is often revealed by
      standard blood tests. We present here a clinical case of renal nephretic colic
      occurring during the third trimester of a fourth pregnancy. Our investigations
      led to the diagnosis of primary hyperparathyroidism which was successfully
      treated. Hyperparathyroidism during pregnancy is associated with a high incidence
      of fetal and maternal complications, essentially neonatal hypocalcemia. In utero
      death is rare but has been reported. Calcium metabolism during pregnancy is
      dependent on PTHrp. The surgical option is usually taken during the second
      trimester but can only be proposed during the third trimester in the event of
      medically resistant hypercalcemia.

PMID- 15247878
TI  - [Glimepiride-induced cute cholestatic hepatitis].

PMID- 15247879
TI  - [Emphysematous cystitis].
AB  - The prevalence of urinary tract infection is high in patients with diabetes
      mellitus. The presence of gas in the bladder lumen or wall constitute
      emphysematous cystitis. This disease is usually observed in diabetic patients.
      Early diagnosis and treatment are important factors for the outcome and absence
      of after-effects. We report the case of a 85 Year old women who was admitted to
      the hospital because of a gastrointestinal bleeding and subsequently developed an
      emphysematous cystitis. We present a comprehensive review of the literature and
      discuss pathogenesis, diagnosis and treatment of this condition.

PMID- 15247880
TI  - [AFSSAPS recommendations about menopause].

PMID- 15247881
TI  - Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases
      and other apoptotic molecules as targets for drug development.
AB  - Mapping of the human and other eukaryotic genomes has provided the
      pharmacological industry with excellent models for drug discovery. Control of
      cell proliferation, differentiation, activation and cell removal is crucial for
      the development and existence of multicellular organisms. Each cell cycle
      progression, with sequences of DNA replication, mitosis, and cell division, is a
      tightly controlled and complicated process that, when deregulated, may become
      dangerous not only to a single cell, but also to the whole organism. Regulation
      and the proper control of the cell cycle and of programmed cell death (apoptosis)
      is therefore essential for mammalian development and the homeostasis of the
      immune system. The molecular networks that regulate these processes are critical
      targets for drug development, gene therapy, and metabolic engineering. In
      addition to the primary, intracellular apoptotic suicide machinery, components of
      the immune system can detect and remove cells and tissue fragments that no longer
      serve their defined functions. In this review we will focus on apoptotic pathways
      converging on caspase family proteases, summarizing pharmacological attempts that
      target genes, proteins, and intermolecular interactions capable of modulating
      apoptosis and the inflammatory response. The upcoming pharmacological development
      for treatment of acute pathologies, such as sepsis, SIRS, stroke, traumatic brain
      injury, myocardial infarction, spinal cord injury, acute liver failure, as well
      as chronic disorders such as Huntington's disease, Parkinson's disease, ALS, and
      rheumatoid arthritis, will be discussed in details. We also suggest new potential
      molecular targets that may prove to be effective in controlling apoptosis and the
      immune response in vivo.

PMID- 15247882
TI  - Mechanisms of type I interferon signaling in normal and malignant cells.
AB  - Type I interferons (IFNs) are cytokines that induce multiple biological effects
      on target cells, including antiviral, antiproliferative, and immunomodulatory
      activities. Consistent with the pleiotropic nature of these cytokines, multiple
      signaling pathways are activated during binding of IFNs to the type I IFN
      receptor. An important signaling cascade activated by type I IFNs is the Jak-Stat
      pathway. Activation of the Tyk-2 and Jak-1 kinases, and downstream formation of
      various Stat complexes, mediates IFN-dependent gene transcription for IFN
      stimulated genes. In addition to the classic Jak-Stat pathway, type I IFNs
      activate multiple other pathways, including the insulin receptor substrate
      phosphatidylinositol 3'-kinase cascade, the CBL-CrkL pathway, and mitogen
      activated protein kinase pathways. There is accumulating evidence that non-Stat
      IFN-regulated signaling pathways play important roles in the generation of the
      antiproliferative effects of type I IFNs. In this review, the regulation of
      various signaling cascades by the type I IFN receptor is summarized and an update
      on recent advances in the field is provided.

PMID- 15247883
TI  - Targeting the chemokine network in renal inflammation.
AB  - Chemokines and their receptors are involved in the pathogenesis of renal
      diseases. They mediate leukocyte recruitment and activation during initiation as
      well as progression of renal inflammation. Infiltrating leukocyte subpopulations
      contribute to renal damage by releasing inflammatory and profibrotic cytokines.
      All intrinsic renal cells are capable of chemokine secretion on stimulation in
      vitro. Expression of inflammatory chemokines correlates with renal damage and
      local accumulation of chemokine receptor-bearing leukocytes in a variety of
      animal models of renal diseases as well as in human biopsy studies. Chemokines
      and their respective receptors could represent new targets for therapeutic
      intervention in renal inflammatory disease states that often tend to progress to
      end-stage renal disease. This article summarizes the present data on the role of
      chemokines and their receptors in renal inflammation with special emphasis on our
      efforts to identify the chemokine receptors CCR1 and CCR2 as promising targets
      for therapeutic intervention.

PMID- 15247884
TI  - Tracking lymphocytes in vivo.
AB  - The ability to track antigen (Ag)-specific lymphocyte populations in vivo has
      greatly increased our understanding of the location and functional status of
      these cells throughout the course of an immune response. Recent technical
      advances have enhanced researchers' capability to follow migration, activation
      and cellular interactions of Ag-specific lymphocytes in situ. It is now possible
      to monitor changes in T cell subsets, co-stimulatory molecules, and chemokine
      expression within the physiological context of secondary lymphoid organs.
      Furthermore, the Ag-presenting cell-T cell interaction can be studied,thus
      dissecting the role and timing of Ag presentation of particular dendritic cell
      subsets in the initiation of the immune response. The capacity to adoptively
      transfer small populations of Ag-specific T lymphocytes has also increased our
      knowledge of the physiologically important role of regulatory T cells in
      autoimmunity and immunosuppression. New fluorescence imaging techniques such as
      multicolor video microscopy, laser scanning cytometry, and multiphoton tissue
      imaging have provided new ways in which researchers can track cellular changes
      within Ag-specific lymphocytes in vivo. This review summarizes some of the ways
      in which these techniques have led to discoveries in the role of signaling
      cascades, cell cycle progression, and apoptosis in maintaining an Ag-specific
      immune response.

PMID- 15247885
TI  - Structure of the O-polysaccharide of Proteus mirabilis O19 and reclassification
      of certain Proteus strains that were formerly classified in serogroup O19.
AB  - INTRODUCTION: Bacteria of the genus Proteus are a common cause of urinary tract
      infections. The O-polysaccharide chain of their LPS (O-antigen) defines the
      serological specificity of these bacteria. Based on the immunospecificity of the
      O-antigens, two species, P. mirabilis and P. vulgaris, were classified into 49 O
      serogroups, and more O-serogroups for strains of these species and P. penneri
      have been subsequently proposed. MATERIAL AND METHODS: The lipopolysaccharide of
      P.mirabilis CCUG 19011 from serogroup O19 was degraded under mildly acidic and
      mildly alkaline conditions. Polysaccharides thus obtained were studied by
      chemical methods, including O -deacetylation, sugar and methylation analyses, and
      1H- and 13C-NMR spectroscopy. Antisera were obtained by immunization of New
      Zealand white rabbits with heat-killed bacteria. In serological studies, enzyme
      immunosorbent assay, passive hemolysis test, and inhibition of passive hemolysis
      were used. RESULTS: The following structure of the O-polysaccharide repeating
      unit was established:-->3)- beta-D-GlcrhoNAc-(1-->3)- alpha-D-GalrhoNAc4,6(R-Pyr)
      (1-->4)- a-D-GalrhoA-(1-->3) alpha-L-Rhap2Ac-(1-->where R-Pyr is (R)-1
      carboxyethylidene (an acetal-linked pyruvic acid). This structure is
      significantly different from the O-polysaccharide structures of P. vulgaris,
      P.hauseri and P. penneri strains from the same Proteus serogroup O19.
      CONCLUSIONS: Based on immunochemical studies of the lipopolysaccharides, it is
      suggested 1) to keep P. vulgaris CCUG 4654 and P. penneri 31 in serogroup O19 as
      two subgroups, 2) to reclassify P. mirabilis CCUG 19011 into a new Proteus
      serogroup, O51, and 3) to classify serologically related strains, including P.
      vulgaris ATCC 49990, P. hauseri> 1732-80 and 1086-80, P. penneri 15, and some
      other P. penneri strains, in yet another Proteus serogroup, O52.

PMID- 15247886
TI  - Human sera with precipitating antibodies to human soluble immune complexes. A
      brief communication.
AB  - INTRODUCTION: Previous numerous papers by the senior author dealt with the human
      serum factor referred to as anti-antibody which is specifically directed against
      IgG antibodies that underwent molecular transformation in the course of the
      reactions with their corresponding antigens. The reactions of this serum factor
      could be conveniently detected by means of agglutination of Rh-positive
      erythrocytes sensitized by anti Rh antibodies. No precipitation tests could be
      developed. MATERIAL AND METHODS: Most studies were conducted by means of double
      diffusion in gel precipitation. RESULTS: A rheumatoid arthritis serum, G, was
      noted that produced a strong reaction of double diffusion in gel precipitation
      with serum samples of a renal graft recipient, T. Further screening detected one
      more rheumatoid arthritis serum reacting with T; of 28 sera from renal graft
      recipients, 6 reacted in a similar way to T, but the reactions were considerably
      weaker and poorly reproducible. Evidence was presented that the precipitin in the
      two rheumatoid arthritis sera under study had properties of previously described
      anti-antibody. CONCLUSIONS: Sera with precipitating anti-antibodies may serve as
      exquisite reagents for detection of soluble immune complexes in human sera.

PMID- 15247887
TI  - Serum concentrations of MCP-1 and RANTES in patients during aortic surgery: the
      relationship with ischemia-reperfusion.
AB  - INTRODUCTION: Surgical trauma is associated with depression of the immune system,
      which results in a high complication rate following abdominal aortic aneurysm
      (AAA) repair. Monocyte chemotactic protein-1 (MCP-1) and regulated-on-activation
      normal T cell expressed and secreted (RANTES) protein are important mediators of
      the immune and inflammatory response. The aim of this study was to determine
      whether there is any relationship between MCP-1 or RANTES and operative injury
      and ischemia-reperfusion during AAA surgery in human. MATERIAL AND METHODS:
      Peripheral blood samples were taken from 12 patients before surgery, after
      anesthesia induction, before unclamping of aorta (PreXoff), 90 min after
      unclamping (90 minXoff), and at 24 and 48 h after surgery. RESULTS: The MCP-1 and
      RANTES serum concentrations were measured with the ELISA technique. MCP-1
      concentration significantly increased after reperfusion (90 minXoff) in
      comparison with the PreXoff level (p=0.001). Twenty-four hours after AAA repair,
      MCP-1 significantly decreased 269-225 pg/ml (p=0.005) and reached preoperative
      value. RANTES level was higher in AAA patients before surgery than in controls
      (p=0.025) and decreased significantly after ischemia-reperfusion to 13 ng/ml (p<
      0.001) at 90 minXoff. We showed increases in RANTES concentration to 26 ng/ml on
      the 1st and to 31 ng/ml on the 2nd day after surgery (p=0.020, p=0.012,
      respectively) compared with the 90 min Xoff level. CONCLUSIONS: Ischemia
      reperfusion during AAA repair results in an increase in MCP-1 and decrease in
      RANTES concentrations in serum. The changes in chemokine concentrations may
      influence the development of immunosuppression after AAA repair, contributing to
      the postoperative course.

PMID- 15247888
TI  - Evaluation of selected peripheral blood leukocyte functions in patients with
      various forms of periodontal disease.
AB  - INTRODUCTION: Periodontitis (P) is an infectious disease that develops in the
      supporting tissues of the tooth. One of the risk factors leading to it may be
      dysfunction of some immune system cells. Therefore, the object of the study was
      to assess selected functions of peripheral blood leukocytes in patients with
      various forms of P. As leukocytes are able to secrete interleukin (IL)-4 and IL
      6, concentrations of their soluble receptors and the expression of their membrane
      receptors were investigated. MATERIAL AND METHODS: Twenty generally healthy
      subjects with aggressive (AP)and chronic periodontitis (CP)were enrolled in the
      study. The control group consisted of 8 healthy subjects,with no changes in
      periodontium. Peripheral blood mononuclear cells (PBMCs) were isolated and
      cultured. Levels of IL-4,IL-6,and their soluble receptors sIL-4R and sIL-6R were
      determined in the supernatant by ELISA. The expressions of cell surface IL-4R and
      IL-6R were assayed on PBMC using flow cytometry. RESULTS: No statistically
      significant differences were found in the selected parameters between people with
      periodontal disease and healthy controls. However, in subjects with AP, there was
      an increasing tendency in IL-6 concentration and IL-4R expression on PBMCs.
      CONCLUSIONS: Our results show that leukocytes play a significant part in P and
      their activity is probably lesion-dependent. Estimation of the cytokines secreted
      by leukocytes may facilitate differentiation and prognosis of the disease
      progression.

PMID- 15247890
TI  - Getting organized in a complex health care world.

PMID- 15247891
TI  - Issues in credentialing CAM providers.

PMID- 15247892
TI  - Supreme Court decides important accessibility case.

PMID- 15247893
TI  - Dealing with cranky doctors.

PMID- 15247895
TI  - Case management communication on a shoestring budget.

PMID- 15247896
TI  - Clinical practice guidelines: a tool for case managers.

PMID- 15247897
TI  - The economic impact of case management.

PMID- 15247898
TI  - Asthma management at the source.

PMID- 15247900
TI  - Preventing laptop theft.

PMID- 15247901
TI  - Independent component analysis of microarray data in the study of endometrial
      cancer.
AB  - Gene microarray technology is highly effective in screening for differential gene
      expression and has hence become a popular tool in the molecular investigation of
      cancer. When applied to tumours, molecular characteristics may be correlated with
      clinical features such as response to chemotherapy. Exploitation of the huge
      amount of data generated by microarrays is difficult, however, and constitutes a
      major challenge in the advancement of this methodology. Independent component
      analysis (ICA), a modern statistical method, allows us to better understand data
      in such complex and noisy measurement environments. The technique has the
      potential to significantly increase the quality of the resulting data and improve
      the biological validity of subsequent analysis. We performed microarray
      experiments on 31 postmenopausal endometrial biopsies, comprising 11 benign and
      20 malignant samples. We compared ICA to the established methods of principal
      component analysis (PCA), Cyber-T, and SAM. We show that ICA generated patterns
      that clearly characterized the malignant samples studied, in contrast to PCA.
      Moreover, ICA improved the biological validity of the genes identified as
      differentially expressed in endometrial carcinoma, compared to those found by
      Cyber-T and SAM. In particular, several genes involved in lipid metabolism that
      are differentially expressed in endometrial carcinoma were only found using this
      method. This report highlights the potential of ICA in the analysis of microarray
      data.

PMID- 15247902
TI  - Mitochondrial p53 levels parallel total p53 levels independent of stress response
      in human colorectal carcinoma and glioblastoma cells.
AB  - p53 can eliminate damaged cells through the induction of mitochondria-mediated
      apoptosis. Recent observations have provided strong evidence that a fraction of
      total p53 translocates to mitochondria specifically in response to a death
      stimulus. Unexpectedly, mutant p53, which is expressed at much higher levels than
      wild type in unstressed cells, is apparently always present at the mitochondria,
      independent of apoptotic signal. This prompted us to ask whether cell lines with
      intact p53-dependent apoptosis and cell cycle arrest pathways exist in which the
      mitochondrial localization of wild-type p53, like that of mutant, is independent
      of a death stimulus and instead, correlates with the total p53 levels. Here, we
      document that human HCT116 colorectal carcinoma cells treated with adriamycin or
      5-fluorouracil (5FU) can accumulate total p53 to equally high levels, and
      mitochondrial p53 to proportionate levels, although only 5FU treatment provoked
      p53-dependent apoptosis. Along the same line, HCT116 derivatives with increased
      basal p53 levels, and glioblastoma cells with a doxycycline-inducible p53, also
      revealed proportionate mitochondrial p53 levels, and even unstressed HCT116 cells
      had some p53 located at the mitochondria. Finally, mitochondrial and total p53
      showed distinct post-translational modifications. Thus, cell lines exist in which
      the mitochondrial p53 levels parallel total levels independent of apoptosis.

PMID- 15247903
TI  - Modeling of lung cancer by an orthotopically growing H460SM variant cell line
      reveals novel candidate genes for systemic metastasis.
AB  - Endobronchial implantation of NCI-H460 cells into the nude rat generates a
      primary lung tumor with mediastinal lymph node spread, but rarely systemic
      metastases. We isolated tumor cells from mediastinal nodes, orthotopically
      reimplanted the cells into nude rats and repeated this four times to derive a
      cell line, designated H460SM, that spontaneously metastasizes to bone, kidney,
      brain, soft tissue and contralateral lung. H460SM cells demonstrated higher
      invasive activity in vitro than parental NCI-H460 cells. Spectral karyotyping
      revealed a new inversion within 17q and loss of an extra normal copy of
      chromosome 14 present in parental NCI-H460 cells. Expression profiling of
      orthotopic primary tumors revealed differential expression of 360 genes. Of
      these, 173 were represented in the probe set of a 19.2K OCI cDNA microarray
      previously used to profile the gene expression of surgically resected lung cancer
      specimens. We have computationally validated clinical importance of these genes
      by using in silico analysis of 18 cases of pulmonary adenocarcinoma, which were
      split into two patient groups with markedly different clinical outcome. The model
      identifies additional novel candidate genes for the progression of lung cancer to
      systemic metastases and poor prognosis.

PMID- 15247904
TI  - Mechanisms underlying lack of insulin-like growth factor-binding protein-3
      expression in non-small-cell lung cancer.
AB  - Expression of insulin-like growth factor-binding protein-3, which (IGFBP-3)
      inhibits the proliferation of non-small-cell lung cancer (NSCLC) cells by
      inducing apoptosis, is lost in about half of stage I NSCLC cases. Since promoter
      methylation can silence gene expression, we investigated whether hypermethylation
      of the IGFBP-3 promoter is involved in loss of IGFBP-3 expression in NSCLC. We
      found the IGFBP-3 promoter to be methylated in seven of 13 NSCLC cell lines and
      in 16 of 23, seven of 9, eight of 11, and six of six tumor specimens from
      patients with stage I, II, III, and IV NSCLC, respectively. Methylation status
      correlated with IGFBP-3 mRNA and protein levels in a subset of NSCLC cell lines
      tested in our study. However, treatment with 5'-aza-2'-deoxycytidine (5'-aza-dC)
      restored IGFBP-3 expression in four of seven NSCLC cell lines with the methylated
      promoter, suggesting that multiple mechanisms regulate IGFBP-3 expression in
      NSCLC. Gel shift and chromatin immunoprecipitation assays showed that methylation
      of the Sp-1/Sp-3-binding element in the IGFBP-3 promoter influenced the binding
      of Sp-1, methyl-CpG-binding protein-2 (MeCP2), and histone deacetylase (HDAC). A
      luciferase construct expressing IGFBP-3 promoter in which the Sp-1/Sp-3 binding
      element was methylated showed significantly reduced transcriptional activity. The
      reduction in promoter activity was further suppressed by overexpression of MeCP2,
      which was rescued by 5'-aza-dC. Thus interference with Sp-1 transactivation by
      MeCP2 may contribute to the transcriptional defect of IGFBP-3 expression in NSCLC
      cells with methylated promoter.

PMID- 15247905
TI  - SP100 expression modulates ETS1 transcriptional activity and inhibits cell
      invasion.
AB  - The ETS1 transcription factor is a member of the Ets family of conserved sequence
      specific DNA-binding proteins. ETS1 has been shown to play important roles in
      various cellular processes such as proliferation, differentiation, lymphoid
      development, motility, invasion and angiogenesis. These diverse roles of ETS1 are
      likely to be dependent on specific protein interactions. To identify proteins
      that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we
      describe the functional interaction between SP100 and ETS1. SP100 protein
      interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear
      bodies and ETS1 expression alters the nuclear body morphology in living cells.
      SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA
      promoters in a dose-dependent manner, decreases the expression of these
      endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the
      invasion of breast cancer cells and is induced by Interferon-alpha, which has
      been shown to inhibit the invasion of cancer cells. These data demonstrate that
      SP100 modulates ETS1-dependent biological processes.

PMID- 15247906
TI  - Evidence that Sp1 positively and Sp3 negatively regulate and androgen does not
      directly regulate functional tumor suppressor 15-lipoxygenase 2 (15-LOX2) gene
      expression in normal human prostate epithelial cells.
AB  - In this project, we studied the gene regulation of 15-lipoxygenase 2 (15-LOX2),
      the most abundant arachidonate-metabolizing LOX in adult human prostate and a
      negative cell-cycle regulator in normal human prostate (NHP) epithelial cells.
      Through detailed in silico promoter examination and promoter deletion and
      activity analysis, we found that several Sp1 sites (i.e., three GC boxes and one
      CACCC box) in the proximal promoter region play a critical role in regulating 15
      LOX2 expression in NHP cells. Several pieces of evidence further suggest that the
      Sp1 and Sp3 proteins play a physiologically important role in positively and
      negatively regulating the 15-LOX2 gene expression, respectively. First, mutations
      in the GC boxes affected the 15-LOX2 promoter activity. Second, both Sp1 and Sp3
      proteins were detected in the protein complexes that bound the GC boxes revealed
      by electrophoretic mobility shift assay. Third, importantly, inhibition of Sp1
      activity or overexpression of Sp3 both inhibited the endogenous 15-LOX2 mRNA
      expression. Since 15-LOX2 is normally expressed in the prostate luminal
      epithelial cells, we subsequently explored whether androgen/androgen receptor may
      directly regulate its gene expression. The results indicate that androgen does
      not directly regulate 15-LOX2 gene expression. Together, these observations
      provide insight on how 15-LOX2 gene expression may be regulated in NHP cells.

PMID- 15247907
TI  - Structural basis for Ca(2+)-induced activation of human PAD4.
AB  - Peptidylarginine deiminase 4 (PAD4) is a Ca(2+)-dependent enzyme that catalyzes
      the conversion of protein arginine residues to citrulline. Its gene is a
      susceptibility locus for rheumatoid arthritis. Here we present the crystal
      structure of Ca(2+)-free wild-type PAD4, which shows that the polypeptide chain
      adopts an elongated fold in which the N-terminal domain forms two immunoglobulin
      like subdomains, and the C-terminal domain forms an alpha/beta propeller
      structure. Five Ca(2+)-binding sites, none of which adopt an EF-hand motif, were
      identified in the structure of a Ca(2+)-bound inactive mutant with and without
      bound substrate. These structural data indicate that Ca(2+) binding induces
      conformational changes that generate the active site cleft. Our findings identify
      a novel mechanism for enzyme activation by Ca(2+) ions, and are important for
      understanding the mechanism of protein citrullination and for developing PAD
      inhibiting drugs for the treatment of rheumatoid arthritis.

PMID- 15247908
TI  - PH domain of ELMO functions in trans to regulate Rac activation via Dock180.
AB  - The members of the Dock180 superfamily of proteins are novel guanine nucleotide
      exchange factors (GEF) for Rho family GTPases and are linked to multiple
      biological processes from worms to mammals. ELMO is a critical regulator of
      Dock180, and the Dock180-ELMO complex functions as a bipartite GEF for Rac. We
      identified a mechanism wherein the PH domain of ELMO, by binding the Dock180-Rac
      complex in trans, stabilizes Rac in the nucleotide-free transition state.
      Mutagenesis studies reveal that this ELMO PH domain-dependent regulation is
      essential for the Dock180-ELMO complex to function in phagocytosis and cell
      migration. Genetic rescue studies in Caenorhabditis elegans using ELMO and its
      homolog CED-12 support the above observations in vivo. These data reveal a new
      mode of action of PH domains and a novel, evolutionarily conserved mechanism by
      which a bipartite GEF can activate Rac.

PMID- 15247909
TI  - A buckling-based metrology for measuring the elastic moduli of polymeric thin
      films.
AB  - As technology continues towards smaller, thinner and lighter devices, more
      stringent demands are placed on thin polymer films as diffusion barriers,
      dielectric coatings, electronic packaging and so on. Therefore, there is a
      growing need for testing platforms to rapidly determine the mechanical properties
      of thin polymer films and coatings. We introduce here an elegant, efficient
      measurement method that yields the elastic moduli of nanoscale polymer films in a
      rapid and quantitative manner without the need for expensive equipment or
      material-specific modelling. The technique exploits a buckling instability that
      occurs in bilayers consisting of a stiff, thin film coated onto a relatively
      soft, thick substrate. Using the spacing of these highly periodic wrinkles, we
      calculate the film's elastic modulus by applying well-established buckling
      mechanics. We successfully apply this new measurement platform to several systems
      displaying a wide range of thicknessess (nanometre to micrometre) and moduli (MPa
      to GPa).

PMID- 15247910
TI  - Electrochemical epitaxial polymerization of single-molecular wires.
AB  - The fabrication of organized molecular-scale structures is key to realizing high
      performance molecular- and conjugated-polymer devices. Here, we demonstrate a
      unique single-molecular processing technique using electrochemistry, termed
      'electrochemical epitaxial polymerization'. This technique is based on step-by
      step electropolymerization of the monomer by applying voltage pulses to a monomer
      electrolyte solution that also contains iodine. Using this technique, we observe
      the formation of high-density arrays of single conjugated-polymer wires as long
      as 75 nm on the surface of a Au(111) electrode. Our findings unveil the mechanism
      of electropolymerization, showing that the conjugated polymer wires grow from
      nuclei adsorbed on the iodine-covered Au(111) surface. The results may also open
      the door to mass-production of molecular-scale devices based on conjugated
      polymers.

PMID- 15247911
TI  - A role for Streptococcus pneumoniae in virus-associated pneumonia.
AB  - Here we show, in a double-blind, randomized, placebo-controlled trial in 37,107
      fully immunized infants in Soweto, South Africa, that a 9-valent pneumococcal
      conjugate vaccine, PncCV, prevents 31% (95% confidence interval = 15-43%) of
      pneumonias associated with any of seven respiratory viruses in children in
      hospital. These data suggest that the pneumococcus has a major role in the
      development of pneumonia associated with these viruses and that viruses
      contribute to the pathogenesis of bacterial pneumonia.

PMID- 15247912
TI  - Staphylococcus aureus protein A induces airway epithelial inflammatory responses
      by activating TNFR1.
AB  - Staphylococcus aureus is a major human pathogen that is associated with diverse
      types of local and systemic infection characterized by inflammation dominated by
      polymorphonuclear leukocytes. Staphylococci frequently cause pneumonia, and these
      clinical isolates often have increased expression of protein A, suggesting that
      this protein may have a role in virulence. Here we show that TNFR1, a receptor
      for tumor-necrosis factor-alpha (TNF-alpha) that is widely distributed on the
      airway epithelium, is a receptor for protein A. We also show that the protein A
      TNFR1 signaling pathway has a central role in the pathogenesis of staphylococcal
      pneumonia.

PMID- 15247913
TI  - An efficient method to make human monoclonal antibodies from memory B cells:
      potent neutralization of SARS coronavirus.
AB  - Passive serotherapy can confer immediate protection against microbial infection,
      but methods to rapidly generate human neutralizing monoclonal antibodies are not
      yet available. We have developed an improved method for Epstein-Barr virus
      transformation of human B cells. We used this method to analyze the memory
      repertoire of a patient who recovered from severe acute respiratory syndrome
      coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific
      for different viral proteins, including 35 antibodies with in vitro neutralizing
      activity ranging from 10(-8)M to 10(-11)M. One such antibody confers protection
      in vivo in a mouse model of SARS-CoV infection. These results show that it is
      possible to interrogate the memory repertoire of immune donors to rapidly and
      efficiently isolate neutralizing antibodies that have been selected in the course
      of natural infection.

PMID- 15247914
TI  - CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at
      the immunological synapse.
AB  - How T cells respond with extraordinary sensitivity to minute amounts of agonist
      peptide and major histocompatibility complex (pMHC) molecules on the surface of
      antigen-presenting cells bearing large numbers of endogenous pMHC molecules is
      not understood. Here we present evidence that CD4 affects the responsiveness of T
      helper cells by controlling spatial localization of the tyrosine kinase Lck in
      the synapse. This finding, as well as further in silico and in vitro experiments,
      led us to develop a molecular model in which endogenous and agonist pMHC
      molecules act cooperatively to amplify T cell receptor signaling. At the same
      time, activation due to endogenous pMHC molecules alone is inhibited. A key
      feature is that the binding of agonist pMHC molecules to the T cell receptor
      results in CD4-mediated spatial localization of Lck, which in turn enables
      endogenous pMHC molecules to trigger many T cell receptors. We also discuss
      broader implications for T cell biology, including thymic selection, diversity of
      the repertoire of self pMHC molecules and serial triggering.

PMID- 15247915
TI  - CD8+ T cell contraction is controlled by early inflammation.
AB  - Pathogen-specific CD8(+) T cells expand in number after infection and then their
      numbers invariably contract by 90-95%, leaving a stable memory cell pool. The
      chief features of this response are programmed early after infection; however,
      the factors regulating contraction are mostly undefined. Here we show that
      antibiotic treatment before Listeria monocytogenes infection induced numbers of
      protective memory CD8(+) T cells similar to those in control infected mice, by a
      pathway without contraction. The absence of contraction correlated with decreased
      early inflammation and interferon-gamma production and an increased fraction of
      CD8(+) T cells expressing the interleukin 7 receptor at the peak of the response.
      Thus, contraction is controlled by early inflammation but is not essential for
      the generation of protective memory CD8(+) T cells after infection.

PMID- 15247916
TI  - A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with
      type 1 diabetes.
AB  - Previous studies have suggested more than 20 genetic intervals that are
      associated with susceptibility to type 1 diabetes (T1D), but identification of
      specific genes has been challenging and largely limited to known candidate genes.
      Here, we report evidence for an association between T1D and multiple single
      nucleotide polymorphisms in 197 kb of genomic DNA in the IDDM5 interval. We
      cloned a new gene (SUMO4), encoding small ubiquitin-like modifier 4 protein, in
      the interval. A substitution (M55V) at an evolutionarily conserved residue of the
      crucial CUE domain of SUMO4 was strongly associated with T1D (P = 1.9 x 10(-7)).
      SUMO4 conjugates to I kappa B alpha and negatively regulates NF kappa B
      transcriptional activity. The M55V substitution resulted in 5.5 times greater NF
      kappa B transcriptional activity and approximately 2 times greater expression of
      IL12B, an NF kappa B-dependent gene. These findings suggest a new pathway that
      may be implicated in the pathogenesis of T1D.

PMID- 15247917
TI  - Evidence for nucleosome depletion at active regulatory regions genome-wide.
AB  - The identification of nuclease-hypersensitive sites in an active globin gene and
      in the 5' regions of fruit fly heat shock genes first suggested that chromatin
      changes accompany gene regulation in vivo. Here we present evidence that the
      basic repeating units of eukaryotic chromatin, nucleosomes, are depleted from
      active regulatory elements throughout the Saccharomyces cerevisiae genome in
      vivo. We found that during rapid mitotic growth, the level of nucleosome
      occupancy is inversely proportional to the transcriptional initiation rate at the
      promoter. We also observed a partial loss of histone H3 and H4 tetramers from the
      coding regions of the most heavily transcribed genes. Alterations in the global
      transcriptional program caused by heat shock or a change in carbon source
      resulted in an increased nucleosome occupancy at repressed promoters, and a
      decreased nucleosome occupancy at promoters that became active. Nuclease
      hypersensitive sites occur in species from yeast to humans and result from
      chromatin perturbation. Given the conservation of sequence and function among
      components of both chromatin and the transcriptional machinery, nucleosome
      depletion at promoters may be a fundamental feature of eukaryotic transcriptional
      regulation.

PMID- 15247918
TI  - Complex SNP-related sequence variation in segmental genome duplications.
AB  - There is uncertainty about the true nature of predicted single-nucleotide
      polymorphisms (SNPs) in segmental duplications (duplicons) and whether these
      markers genuinely exist at increased density as indicated in public databases. We
      explored these issues by genotyping 157 predicted SNPs in duplicons and control
      regions in normal diploid genomes and fully homozygous complete hydatidiform
      moles. Our data identified many true SNPs in duplicon regions and few paralogous
      sequence variants. Twenty-eight percent of the polymorphic duplicon sequences we
      tested involved multisite variation, a new type of polymorphism representing the
      sum of the signals from many individual duplicon copies that vary in sequence
      content due to duplication, deletion or gene conversion. Multisite variations can
      masquerade as normal SNPs when genotyped. Given that duplicons comprise at least
      5% of the genome and many are yet to be annotated in the genome draft, effective
      strategies to identify multisite variation must be established and deployed.

PMID- 15247919
TI  - Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia
      neurons to switch fate.
AB  - Tactile information is perceived by a heterogeneous population of specialized
      neurons. Neurotrophin receptors (the receptor tyrosine kinases, Trks) mark the
      major classes of these sensory neurons: TrkA is expressed in neurons that sense
      temperature and noxious stimuli, and TrkC is expressed in proprioceptive neurons
      that sense body position. Neurotrophin signaling through these receptors is
      required for cell survival. To test whether neurotrophins have an instructive
      role in sensory specification, we expressed rat TrkC from the TrkA (also known as
      Ntrk1) locus in mice. The surviving presumptive TrkA-expressing neurons adopted a
      proprioceptive phenotype, indicating that neurotrophin signaling can specify
      sensory neuron subtypes.

PMID- 15247920
TI  - Olfactory receptor neuron axon targeting: intrinsic transcriptional control and
      hierarchical interactions.
AB  - From insects to mammals, olfactory receptor neurons (ORNs) expressing a common
      olfactory receptor target their axons to specific glomeruli with high precision.
      Here we show in Drosophila that the POU transcription factor Acj6 controls the
      axon targeting specificity of a subset of ORN classes, as defined by the
      olfactory receptors that they express. Of these classes, some require Acj6 cell
      autonomously, whereas others require Acj6 cell-nonautonomously. Mosaic analyses
      show that cooperative targeting occurs between axon terminals of the same ORN
      classes and that there are hierarchical interactions among different ORN classes.
      We propose that the precision of ORN axon targeting derives from both intrinsic
      transcriptional control and extensive axon-axon interactions.

PMID- 15247921
TI  - Specification of a DNA replication origin by a transcription complex.
AB  - In early Xenopus development, transcription is repressed and DNA replication
      initiates at non-specific sites. Here, we show that a site-specific DNA
      replication origin can be induced in this context by the assembly of a
      transcription domain. Deletion of the promoter element abolishes site-specific
      initiation, and its relocalization to an ectopic site induces a new origin of
      replication. This process does not require active transcription, and
      specification of the origin occurs mainly through a decrease in non-specific
      initiation at sites distant from the promoter. Finally, chromatin
      immunoprecipitation experiments suggest that site-specific acetylation of
      histones favours the selection of the active DNA replication origin. We propose
      that the specification of active DNA replication origins occurs by secondary
      epigenetic events and that the programming of chromatin for transcription during
      development contributes to this selection in higher eukaryotes.

PMID- 15247922
TI  - The mammalian retromer regulates transcytosis of the polymeric immunoglobulin
      receptor.
AB  - Epithelial cells have separate apical and basolateral plasma membrane domains
      with distinct compositions. After delivery to one surface, proteins can be
      endocytosed and then recycled, degraded or transcytosed to the opposite surface.
      Proper sorting into the transcytotic pathway is essential for maintaining
      polarity, as most proteins are endocytosed many times during their lifespan. The
      polymeric immunoglobulin receptor (pIgR) transcytoses polymeric IgA (pIgA) from
      the basolateral to the apical surface of epithelial cells and hepatocytes.
      However, the molecular machinery that controls polarized sorting of pIgR-pIgA and
      other receptors is only partially understood. The retromer is a multimeric
      protein complex, originally described in yeast, which mediates intracellular
      sorting of Vps10p, a receptor that transports vacuolar enzymes. The yeast
      retromer contains two sub-complexes. One includes the Vps5p and Vps17p subunits,
      which provide mechanical force for vesicle budding. The other is the Vps35p
      Vps29p-Vps26p subcomplex, which provides cargo specificity. The mammalian
      retromer binds to the mannose 6-phosphate receptor, which sorts lysosomal enzymes
      from the trans-Golgi network to the lysosomal pathway. Here, we show a function
      for the mammalian Vps35-Vps29-Vps26 retromer subcomplex in promoting pIgR-pIgA
      transcytosis.

PMID- 15247923
TI  - The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans.
AB  - Temporal control of cell division is critical for proper animal development. To
      identify mechanisms involved in developmental arrest of cell division, we
      screened for cell-cycle mutants that disrupt the reproducible pattern of somatic
      divisions in the nematode C. elegans. Here, we show that the cdc-14 phosphatase
      is required for the quiescent state of specific precursor cells. Whereas budding
      yeast Cdc14p is essential for mitotic exit, inactivation of C. elegans cdc-14
      resulted in extra divisions in multiple lineages, with no apparent defects in
      mitosis or cell-fate determination. CDC-14 fused to the green fluorescent protein
      (GFP-CDC-14) localized dynamically and accumulated in the cytoplasm during G1
      phase. Genetic interaction and transgene expression studies suggest that cdc-14
      functions upstream of the cki-1 Cip/Kip inhibitor to promote accumulation of CKI
      1 in the nucleus. Our data support a model in which CDC-14 promotes a
      hypophosphorylated and stable form of CKI-1 required for developmentally
      programmed cell-cycle arrest.

PMID- 15247924
TI  - Dicer is essential for formation of the heterochromatin structure in vertebrate
      cells.
AB  - RNA interference is an evolutionarily conserved gene-silencing pathway in which
      the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs. The
      biological function of the RNAi-related pathway in vertebrate cells is not fully
      understood. Here, we report the generation of a conditional loss-of-function
      Dicer mutant in a chicken-human hybrid DT40 cell line that contains human
      chromosome 21. We show that loss of Dicer results in cell death with the
      accumulation of abnormal mitotic cells that show premature sister chromatid
      separation. Aberrant accumulation of transcripts from alpha-satellite sequences,
      which consist of human centromeric repeat DNAs, was detected in Dicer-deficient
      cells. Immunocytochemical analysis revealed abnormalities in the localization of
      two heterochromatin proteins, Rad21 cohesin protein and BubR1 checkpoint protein,
      but the localization of core kinetochore proteins such as centromere protein
      (CENP)-A and -C was normal. We conclude that Dicer-related RNA interference
      machinery is involved in the formation of the heterochromatin structure in higher
      vertebrate cells.

PMID- 15247925
TI  - Analysis of the transcriptional complexity of Arabidopsis thaliana by massively
      parallel signature sequencing.
AB  - Large-scale sequencing of short mRNA-derived tags can establish the qualitative
      and quantitative characteristics of a complex transcriptome. We sequenced
      12,304,362 tags from five diverse libraries of Arabidopsis thaliana using
      massively parallel signature sequencing (MPSS). A total of 48,572 distinct
      signatures, each representing a different transcript, were expressed at
      significant levels. These signatures were compared to the annotation of the A.
      thaliana genomic sequence; in the five libraries, this comparison yielded between
      17,353 and 18,361 genes with sense expression, and between 5,487 and 8,729 genes
      with antisense expression. An additional 6,691 MPSS signatures mapped to
      unannotated regions of the genome. Expression was demonstrated for 1,168 genes
      for which expression data were previously unknown. Alternative polyadenylation
      was observed for more than 25% of A. thaliana genes transcribed in these
      libraries. The MPSS expression data suggest that the A. thaliana transcriptome is
      complex and contains many as-yet uncharacterized variants of normal coding
      transcripts.

PMID- 15247927
TI  - Helicase-dependent isothermal DNA amplification.
AB  - Polymerase chain reaction is the most widely used method for in vitro DNA
      amplification. However, it requires thermocycling to separate two DNA strands. In
      vivo, DNA is replicated by DNA polymerases with various accessory proteins,
      including a DNA helicase that acts to separate duplex DNA. We have devised a new
      in vitro isothermal DNA amplification method by mimicking this in vivo mechanism.
      Helicase-dependent amplification (HDA) utilizes a DNA helicase to generate single
      stranded templates for primer hybridization and subsequent primer extension by a
      DNA polymerase. HDA does not require thermocycling. In addition, it offers
      several advantages over other isothermal DNA amplification methods by having a
      simple reaction scheme and being a true isothermal reaction that can be performed
      at one temperature for the entire process. These properties offer a great
      potential for the development of simple portable DNA diagnostic devices to be
      used in the field and at the point-of-care.

PMID- 15247926
TI  - UVA inactivates protein tyrosine phosphatases by calpain-mediated degradation.
AB  - UV irradiation causes inflammatory and proliferative cellular responses. We have
      proposed previously that these effects are, to a large extent, caused by the
      ligand-independent activation of several receptor tyrosine kinases due to the
      inactivation of their negative control elements, the protein tyrosine
      phosphatases (PTPs). We examined the mechanism of this inactivation and found
      that, in addition to reversible oxidation of PTPs, UV triggers a novel mechanism:
      induced degradation of PTPs by calpain, which requires both calpain activation
      and substrate PTP oxidative modification. This as yet unrecognized effect of UV
      is irreversible, occurs predominantly with UVA and UVB, the range of wavelengths
      in sunlight that reach the skin surface, and at physiologically relevant doses.

PMID- 15247928
TI  - Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant
      recipients.
AB  - The incidence of invasive fungal infection (IFIs) in hematopoietic stem cell
      transplantation (HSCT) recipients ranges from 10 to 25% with an overall case
      fatality rate of up to 70-90%. Candida and Aspergillus genera remain the two most
      common pathogens. Although fluconazole prophylaxis in this population has been
      moderately effective in reducing mortality due to invasive candidiasis, this
      agent does not have activity against invasive aspergillosis (IA) and other mould.
      Several new agents such as voriconazole and caspofungin have enhanced potency and
      broad-spectrum antifungal activity and show promising results against yeasts and
      filamentous fungi when given as therapy and as chemoprophylaxis. Further, new
      diagnostic tools to detect circulating fungal antigens in biological fluids and
      PCR-based methods to detect species or genus-specific DNA or RNA have been
      developed. Incorporating these techniques along with clinical criteria appear to
      improve the accuracy of preclinical diagnosis of IFIs. Such approaches may alter
      the current treatment strategy from prophylaxis to pre-emptive therapy, thereby
      potentially decreasing cost and toxicity in high-risk patients.

PMID- 15247929
TI  - Transplantation of unrelated placental blood cells in children with high-risk
      sickle cell disease.
AB  - The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic
      cell transplantation in children with high-risk sickle cell disease (SCD). We
      evaluated unrelated placental blood cell transplantation (UPBCT) after a
      preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in
      three children with SCD who had cerebrovascular accidents (CVAs) and did not have
      HLA-matched sib donors. The placental blood cell units were matched with the
      recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels
      above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet
      levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days
      after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two
      grade II, one grade III), and one developed extensive chronic GVHD. One patient
      had graft failure and autologous hematopoietic recovery. Two patients have
      complete donor hematopoietic chimerism without detectable hemoglobin S or
      symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These
      observations demonstrate the feasibility of UPBCT in children with SCD. Further
      studies of UPBCT for SCD are needed but, because of risks of procedure-related
      morbidity and graft rejection, should be restricted to pediatric patients with
      high-risk manifestations of SCD.

PMID- 15247930
TI  - Immunological and electrophysiological investigations of severe ptosis after bone
      marrow transplantation.
AB  - Ocular problems are common in recipients of stem cell transplantation (SCT), but
      ptosis is rarely reported and investigated. Among 346 consecutive SCT recipients,
      severe bilateral ptosis was noticed or reported in six cases (five women and one
      man), all with acute graft-versus-host disease (aGVHD) and chronic graft-versus
      host disease (cGVHD). On univariate analysis, both aGVHD (P=0.001) and cGVHD
      (P<0.001) were associated with post SCT ptosis, while a trend was shown for
      female sex (P=0.086). The median level of anti-acetylcholine receptor antibody
      was significantly higher in ptosis cases than controls with cGVHD (student's t
      test, P=0.01). Antistriated muscle antibody was detected in three cases and was
      not significantly different from controls (Fisher's exact test, P=0.29). Tensilon
      tests were uniformly negative. However in five cases, single fibre electromyogram
      at frontalis muscle showed irregular recruitment effort, suggesting localized
      neuromuscular transmission defect reminiscent of ocular myasthenia gravis (MG).
      Two patients were observed, while three patients did not respond to mestinon or
      steroids treatment and one patient underwent aponeurosis advancement surgery.
      Transplant physicians and ophthalmologists should be aware of the problem of post
      SCT ptosis, which may be related to alloimmune causes of neuromuscular
      transmission block. Diagnosis can be difficult to confirm even with invasive SF
      EMG testing. Most cases warrant conservative treatment due to chronicity, benign
      course and poor response to medication.

PMID- 15247931
TI  - Assessment of the coagulation profile in hemato-oncological patients receiving
      ATG-based conditioning treatment for allogeneic stem cell transplantation.
AB  - Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell
      transplantation (allo-SCT) conditioning regimens to prevent graft rejection and
      graft-versus-host disease. However, ATG was also found to be associated with
      increased incidence of thrombosis during organ transplantation. In the present
      study, we tested the coagulation status of 21 patients with hematologic
      malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG
      based (10) conditioning treatment. We assessed several thrombophilia markers as
      well as circulating total and endothelial microparticles (TMP/EMP) and soluble
      CD40 ligand (CD40L). No significant difference in the mean values of prothrombin
      time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein
      S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic
      thrombophilia markers and levels of EMP, TMP or CD40L was observed between the
      ATG-treated and ATG-untreated patients, as well as before and after conditioning
      in each group separately. Platelet counts decreased significantly in ATG-treated
      patients; however, this decrease was not associated with clinical or laboratory
      evidence of disseminated intravascular coagulation. No patient developed
      thromboembolic event or veno-occlusive liver disease. Our results suggest that
      allo-SCT is not associated with increased hypercoagulability and addition of ATG
      to conditioning regimen has no significant procoagulant effect.

PMID- 15247933
TI  - [Progress in surgical treatment of heart diseases. January 17-18, 2003, Gdansk,
      Poland. Proceeding of a meeting].

PMID- 15247932
TI  - A pilot study of targeted itraconazole prophylaxis in patients with graft-versus
      host disease at high risk of invasive mould infections following allogeneic stem
      cell transplantation.
AB  - Patients with severe graft-versus-host disease (GVHD) requiring intensive
      immunosuppression are at high risk of invasive mould infections (IMI).
      Prophylaxis with an active, oral antifungal agents with reliable absorption in
      this context is desirable. A total of 44 patients at high risk of post
      engraftment IMI received itraconazole solution 2.5 mg/kg b.d. as prophylaxis. Two
      of the first nine patients, in whom bioavailability was compromised due to
      significant vomiting and/or diarrhoea, died of probable or proven invasive
      aspergillus. None of the subsequent 35 patients, some of whom had severe gut GVHD
      and who received liposomal amphotericin B prophylaxis until itraconazole was
      reliably tolerated and absorbed, developed IMI. The overall incidence of IMI was
      substantially lower than in historical controls. Itraconazole was generally well
      tolerated, with five patients (11%) ceasing the drug due to intolerance or
      disturbed liver function. Targeted prophylaxis with oral or parenteral antifungal
      agents in high-risk allograft recipients appears to be effective in reducing the
      incidence of IMI.

PMID- 15247934
TI  - [Mitral valve repair--past, present, future].

PMID- 15247935
TI  - [Degenerative mitral regurgitation--when is surgery indicated?].

PMID- 15247936
TI  - [Degenerative mitral valve regurgitation--surgery outcomes].

PMID- 15247937
TI  - [Ischemic mitral regurgitation--when is surgery indicated?].

PMID- 15247938
TI  - [Ischemic mitral regurgitation--what kind of surgery?].

PMID- 15247939
TI  - [Ischemic mitral regurgitation--surgical outcomes].

PMID- 15247940
TI  - [Atrial size reduction and right pulmonary vein exclusion for treatment of atrial
      fibrillation in mitral valve surgery--preliminary report].

PMID- 15247941
TI  - [Tricuspid valve surgery secondary to mitral and aortal valve replacement].

PMID- 15247942
TI  - [Stentless aortic valve replacement].

PMID- 15247943
TI  - [Combined valve operations and coronary artery bypass grafting].

PMID- 15247944
TI  - [Stentless valves--collaboration of the cardiologist and cardiac surgeon].

PMID- 15247945
TI  - [Coronary artery bypass grafting in severe ischemic left ventricular dysfunction
      (EF<25%)--analysis of short-term and long-term outcomes].

PMID- 15247946
TI  - [Coronary artery bypass grafting in the patients aged 80 and over--own study].

PMID- 15247947
TI  - [Comparison of early outcome in myocardial revascularization with OPCAB and
      CABG].

PMID- 15247948
TI  - [Minimally invasive direct coronary bypass (MIDCAB) for myocardial ischemia].

PMID- 15247949
TI  - [Sequential and individual coronary bypass graft: short-term and long-term
      outcome].

PMID- 15247950
TI  - [Radial artery for coronary bypass graft--own experience].

PMID- 15247951
TI  - [Autologous transplantation of skeletal myoblasts in the treatment of
      postinfarction left heart dysfunction: three-month follow-up].

PMID- 15247952
TI  - [Surgical treatment of ventricular remodelling after myocardial infarction].

PMID- 15247953
TI  - [Gene therapy with phVEGF165 plasmid--preliminary report].

PMID- 15247954
TI  - [Preliminary treatment outcome of cardiovascular operations in patients with
      dialysis-dependent renal failure].

PMID- 15247955
TI  - [Right subclavian artery cannulation in surgery of acute type A aortic
      dissection].

PMID- 15247956
TI  - [Application of thermography in cardiac surgery].

PMID- 15247957
TI  - Short-term endurance training after coronary artery bypass grafting improves
      insulin resistance parameters in patients with hypertension.
AB  - BACKGROUND: It has been shown that short-term exercise training improves insulin
      resistance parameters in patients with ischaemic heart disease. The effects of
      such a rehabilitation programme in patients with hypertension have not been well
      established. AIM: To assess whether short-term endurance training after coronary
      artery bypass grafting (CABG) may improve metabolic parameters and reduce blood
      pressure in patients with hypertension. METHODS: The study group consisted of 30
      male patients (15 with hypertension and 15 normotensive) aged 55+/-2.1 years who
      underwent CABG 1 to 6 months before the initiation of a 3-week endurance
      training. Glucose, insulin and C-peptide blood levels as well as binding and
      degradation of 125I-insulin by erythrocyte receptors were assessed before and
      after the training programme. The effects of training on blood pressure values
      were also evaluated. RESULTS: A significant improvement (p<0.01) in the insulin
      resistance parameters, i.e. binding and degradation of labelled insulin was noted
      only in patients with hypertension. This was accompanied by a significant
      (p<0.05) increase in the HDL-cholesterol level. In the subgroup with
      hypertension, both the exercise systolic and diastolic pressures decreased
      significantly (p<0.05 and p<0.01, respectively), and similar changes were noted
      in the resting systolic and diastolic blood pressures values (p<0.05).
      CONCLUSIONS: Rehabilitation after CABG based on the endurance training was
      especially effective in patients with hypertension in whom beneficial changes in
      some metabolic risk factors of ischaemic heart disease as well as the reduction
      in the blood pressure values were observed.

PMID- 15247958
TI  - Accelerated streptokinase and enoxaparin in ST-segment elevation acute myocardial
      infarction (the ASENOX study).
AB  - BACKGROUND: The streptokinase (SK) regimen (1.5 MU/60 min) has remained unchanged
      in the ST-segment elevation acute myocardial infarction (STEMI) for the last 20
      years. AIM: To compare the efficacy of an accelerated SK (ASK) regimen combined
      with enoxaparin (Enox) or heparin (UFH) with the standard SK and UFH combination
      in STEMI. METHODS: 633 consecutive patients, aged 21-74 years, admitted within 6
      hours after the onset of STEMI, were divided in three groups: (1) ASKEnox
      (n=165): Enox 40 mg. i.v. followed by SK 1.5 MU over 20 min, either as a full
      dose or a double infusion of 0.75 MU over 10 min. separated by 50 min. After SK
      infusion, Enox was administered 1 mg/kg s.c. every 12 hours for 5-7 days; (2)
      ASKUFH (n=264): the same ASK regimen plus UFH 1,000 IU/h for 48-72 hours, (3)
      SSKUFH (n=204): SK 1.5 MU/60 min. plus UFH 1,000 IU/h for 48-72 hours. All
      patients received aspirin. Three coronary reperfusion (CR) criteria were used: 1.
      rapid cessation of chest pain; 2. rapid reduction of ST-segment elevation by more
      than 50% of the initial value; 3. rapid increase in plasma CK and CK-MB with a
      peak in the first 12 hours. RESULTS: The rates of CR in the ASKEnox (77.6%) and
      the ASKUFH (73.5%) groups were similar but both were significantly higher than
      that observed in the SSKUFH group (62.2%) (p=0.002 and 0.013, respectively). The
      30-day mortality rates were similar in the ASKEnox (6.06%) and the ASKUFH (6.81%)
      groups but both were significantly lower than in the SSKUFH group (12.74%)
      (p=0.048 and 0.044, respectively). SK-induced hypotension was more frequent in
      the ASKEnox (39.4%) and ASKUFH (38.3%) groups compared with the SSKUFH group
      (20.6%) (p<0.0001), but it was transient and well tolerated. Haemorrhagic stroke
      occurred in two patients from the SSKUFH and one patient from the ASKUFH groups.
      CONCLUSIONS: ASKEnox and ASKUFH regimens are safe and result in a significantly
      higher rate of CR and a lower in-hospital mortality compared with the traditional
      SSKUFH regimen.

PMID- 15247959
TI  - Prognostic value of angiographic markers of myocardial reperfusion in patients
      treated with primary coronary angioplasty for anterior wall acute myocardial
      infarction.
AB  - BACKGROUND: Modern therapy of acute myocardial infarction (AMI) is aimed at rapid
      and persisting restoration of blood flow in an infarct-related artery (IRA).
      However, in some patients myocardial reperfusion is not achieved in spite of
      effective IRA recanalisation. Myocardial Blush Grade (MBG) is one of the
      angiographic markers useful for the detection of this phenomenon. AIM: To assess
      the prognostic value of MBG in patients with anterior AMI treated with primary
      angioplasty. METHODS: The study group consisted of 104 patients (74 males, 30
      females, mean age 62+/-13 years) treated with primary angioplasty due to anterior
      ST-segment elevation AMI. MBG was assessed after the procedure. The mortality and
      major cardiovascular event (MACE) rates were analysed one and six months after
      AMI. RESULTS: Patients with preserved myocardial reperfusion following
      angioplasty (MBG 2-3, n=64 (61.5%)) had a trend towards lower one-month mortality
      and significantly reduced six-month mortality compared with 40 (38.5%) patients
      with an impaired (MBG 0-1) myocardial reperfusion (3% vs 12.5%, NS; and 6.25% vs
      20%, p<0.05, respectively). The rate of MACE was significantly lower in patients
      with rather than without reperfusion both after one and six months of follow-up
      (9.4% vs 27.5%, p=0.027 and 12.5% vs 42.5%, p<0.001, respectively). Compared with
      patients with a high MBG score, patients with altered reperfusion more frequently
      had diabetes (30% vs 12.5%, p=0.04), hypertension (67.5% vs 45%, p=0.043), longer
      time from the onset of symptoms to balloon inflation (355.9+/-199 min vs 215.5+/
      113 min, p<0.001) and lower left ventricular ejection fraction, measured 3 days
      after AMI (43.3%+/-8 vs 47.4%+/-9, p=0.02). CONCLUSIONS: MBG has a significant
      prognostic value in patients with anterior AMI treated with primary angioplasty.
      Diabetes, hypertension and long delay of treatment are associated with the
      impairment of myocardial reperfusion.

PMID- 15247960
TI  - Atorvastatin treatment decreases inflammatory and proteolytic activity in
      patients with hypercholesterolemia.
AB  - BACKGROUND: Statins have anti-inflammatory and anti-platelet effects, which are
      known as non-lipid effects. Statin treatment can decrease endogenous inflammatory
      response. AIM: To study the effects of atorvastatin on matrix metalloproteinase-9
      (MMP-9) and high sensitive C-reactive protein (hs-CRP) - markers of the
      proteinolytic and inflammatory activity. METHODS: In this prospective study 44
      patients with hypercholesterolemia were randomly assigned into 2 groups; Group 1
      (n=22) treated with atorvastatin and diet for 2 months, and Group 2 (n=22) - diet
      alone. MMP-9 and hs-CRP were measured at baseline and two months later. RESULTS:
      Groups were matched for age, sex and baseline characteristics. Lipid levels
      decreased by 32% (LDL from 153.9+/-26.6 to 94.5+/-20.8 mg/dl, p<0.005) in the
      atorvastatin group and by 9% in the diet alone group. Atorvastatin lowered plasma
      CRP from 5.16+/-1.9 to 2.88+/-1.06 mg/L (p<0.001) and MMP-9 activity from 64.3+/
      28.1 to 35.4+/-20.0 ng/ml (p<0.0001). Atorvastatin-induced reductions in CRP and
      MMP-9 were greater than in the diet alone group. MMP-9 levels did not show
      significant changes in Group 2 after two months of diet. CONCLUSIONS:
      Atorvastatin treatment decreases inflammatory and proteolytic activity in
      patients with hypercholesterolemia.

PMID- 15247961
TI  - Platelet inhibition by increased tirofiban dosing during primary coronary
      angioplasty for ST elevation myocardial infarction.
AB  - BACKGROUND: Platelet receptor IIb/IIIa inhibition during percutaneous coronary
      interventions (PCI) decreases incidence of major adverse cardiac events (MACE).
      These effects directly result from the level of platelet inhibition. Due to
      existing data indicating that standard dosing of tirofiban is insufficient for
      optimal platelet inhibition, we proposed a novel, experimental dosing. AIM: In
      this study we assessed, with the use of Ultegra Rapid Platelet Function Assay
      (RFPA), the level of platelet inhibition with increased tirofiban dosing during
      primary PCI for ST elevation myocardial infarction (STEMI). METHODS: Twenty eight
      patients (22 males, 6 females, mean age 63 years, range 32-78 years) with STEMI
      were included into the study. All patients received 300 mg of aspirin, iv.
      heparin in a dose of 10 000 IU, which was followed by platelet receptor GP
      IIb/IIIa inhibitor tirofiban - 10 micro g/kg iv bolus, 0.4 micro g/kg/min for 30
      min and infusion 0.1 micro g/kg/min continued for 12-24 h. Platelet function was
      assessed with RFPA before tirofiban administration and after 10, 30, 90 minutes
      as well as 8 hours from the initial dose of tirofiban. Baseline fibrinogen
      binding to platelet receptor IIb/IIIa was defined as PAU (platelet aggregation
      unit) and the effects of tirofiban on platelets were expressed as a percentage of
      platelet inhibition. RESULTS: During in-hospital stay, no deaths, re-infarction
      nor recurrences of ischaemia requiring intervention were noted. The mean total
      duration of tirofiban administration was 21 hours. Thrombocytopenia was not
      observed in any patient. Bleeding complications occurred in 5 (17.9%) patients.
      Blood transfusion was required in three patients. The percentages of platelet
      inhibition measured at the pre-specified time-points were 95%, 94%, 91% and 87%,
      respectively. In 32% of patients an inhibition of platelet exceeding 95%,
      measured 10 minutes from the onset of tirofiban infusion, was not achieved. At
      the same time, platelet inhibition <90% was found in only 3 (11%) patients. Eight
      hours from the initiation of tirofiban, platelet inhibition <70% was found in 3
      (11%) patients; of them, two had platelet inhibition <95% when measured 10
      minutes from the onset of therapy with tirofiban. CONCLUSIONS: 1. Increased
      dosing of tirofiban resulted in an enhanced platelet inhibition. 2. Optimal
      platelet inhibition, especially during first minutes of drug administration, was
      not achieved in a substantial number of patients. 3. Increased IIb/IIIa inhibitor
      dosing resulted in a high partial and normal baseline coronary flow in an infarct
      related artery. 4. Increased tirofiban dosing resulted in a relatively high
      bleeding complications rate.

PMID- 15247962
TI  - Low serum triiodothyronine in acute myocardial infarction indicates major heart
      injury.
AB  - AIMS: In patients with acute myocardial infarction (MI), low serum
      triiodothyronine (T3) concentration is commonly associated with a severe clinical
      course. The aim of this prospective study was to investigate whether a severe
      clinical course in patients with low T3 is related to the magnitude of myocardial
      injury assessed by echocardiography. METHODS AND RESULTS: Out of 635 patients
      with MI we enrolled 100 consecutive patients. They were divided in two subgroups:
      group A, 81 patients without clinical hard events (death, resuscitation following
      ventricular tachycardia/vertricular fibrillation, new MI) and group B, 19
      patients in whom at least one of the above hard events occurred during hospital
      stay. Thyroid function tests were performed on day 1, 4 and 7, echocardiographic
      examinations measuring asynergic area (AA), and wall motion score index (WMSI)
      between day 1 and 5 (median 3). A negative correlation was found between plasma
      free triiodothyronine (FT3), concentration and AA (p<0.001), FT3 and WMSI
      (p<0.001) values at all time points. FT3 concentration was lower in group B than
      group A at all time points (p<0.001). CONCLUSIONS: In patients with acute MI, low
      FT3 state is related to the extent of myocardial damage.

PMID- 15247963
TI  - Minimally invasive mitral valve surgery -- first experience in Poland.
AB  - BACKGROUND: Minimally invasive cardiac surgery has been introduced to treat
      various cardiac disorders, predominantly ischaemic heart disease. Its usage in
      valvular disorders has been only recently proposed. AIM: To assess safety and
      efficacy of minimally invasive mitral valve surgery. METHODS: The procedure was
      performed in 10 patients (6 females, 4 males, mean age 59+/-7 years). All but one
      had preserved left ventricular ejection fraction. Two patients underwent mitral
      valvuloplasty, and mitral valve replacement was performed in all remaining cases.
      One procedure was a redo surgery following mitral commisurotomy. RESULTS: In all
      patients the procedure was effective. Prolongation of cardiopulmonary bypass and
      aorta cross-clamping time did not increase the complication rate which included
      one wound infection, one repeated cannulation of the femoral vessels and one
      minor stroke. Rehabilitation process seemed to be shorter than after standard
      procedures. CONCLUSIONS: Minimally invasive mitral valve surgery is a safe and
      alternative method of treatment, and is associated with excellent cosmetic
      results.

PMID- 15247964
TI  - [Surgery for massive pulmonary embolism following coronary angioplasty--a case
      report].
AB  - A case of a 49-year-old female with acute coronary syndrome is presented. The
      patient underwent coronary angioplasty with stent implantation. Due to the
      recurrence of pain and dyspnea a repeated coronary angiography was performed 3
      hours later which confirmed good result of angioplasty. For the next 48 hours a
      local compression on both femoral arteries was maintained and the patient
      received full anticoagulant and antiplatelet treatment. However, clinical
      condition of the patient continued to deteriorate. Echocardiography and spiral
      computerised tomography revealed the presence of a massive pulmonary embolism.
      The patient underwent surgery and fully recovered.

PMID- 15247965
TI  - [Recurrent systemic embolisation in a patient with a large thrombus in left
      ventricular aneurysm--case report].
AB  - A case of a 47-year-old female with the aneurysm of the left ventricle is
      presented. Several days prior to the hospitalization signs of femoral embolism
      emerged, which was treated with embolectomy. Echocardiographic examination
      revealed large thrombus in the cavity of the aneurysm with pedunculated
      surrounding echo. On the second day after the admission the symptoms of renal
      artery embolism occurred. Due to recurrent symptoms of peripheral emboli and the
      lack of a consent for the interventional treatment, fibrinolysis (Actilyse) was
      applied resulting in the reduction of the thrombus mass in the left ventricle.
      Subsequent Doppler ultrasound of the renal arteries showed normal flow pattern.
      During hospitalization general condition has gradually improved and the patient
      was discharged.

PMID- 15247966
TI  - [Acute pulmonary embolism--four case reports].
AB  - Four patients with acute pulmonary embolism are presented. The diagnostic role of
      transesophageal echocardiography and spiral computerised tomography is
      underlined.

PMID- 15247967
TI  - [Massive pulmonary embolism during pregnancy treated with streptokinase and
      complicated by massive haemorrhage--a case report].
AB  - A case of a 27-year-old pregnant female (first trimester) is described. The
      patient was hospitalised due to pregnancy complications and immobilised for 3
      weeks. At the end of this period patient's clinical condition rapidly
      deteriorated and she developed shock, followed by cardiac arrest.
      Echocardiography was consistent with acute pulmonary embolism and the patient
      received streptokinase. This treatment was complicated by a massive bleeding due
      to the rupture of the uterus. She underwent hysterectomy and recovered
      thereafter.

PMID- 15247968
TI  - [Prognosis after acute pulmonary embolism].

PMID- 15247970
TI  - [Electrocardiogram of the month: heart block].

PMID- 15247971
TI  - [Additional structure in aortic arch: atherosclerotic plaque].

PMID- 15247972
TI  - [Angiogram of the month: myocardial infarction].

PMID- 15247973
TI  - [Pharmacologic methods of rate control in atrial fibrillation].

PMID- 15247974
TI  - [Re: Surgical reconstruction of left ventricle after anterior myocardial
      infarction in both women and men, Kardiol Pol. 2004 Jan;60(1):39-47].

PMID- 15247976
TI  - A practical concept for preoperative identification of patients with impaired
      primary hemostasis.
AB  - The findings of a large prospective study designed to identify primary and/or
      secondary hemostatic disorders before surgical interventions are presented. A
      total of 5649 unselected adult patients were enrolled to identify impaired
      hemostasis before surgical interventions. Each patient was asked to answer a
      standardized questionnaire concerning bleeding history. Activated partial
      thromboplastin time (aPTT), prothrombin time (PT), and platelet counts (PC)
      including PFA-100 (platelet function analyzer): collagen-epinephrine (C/E), and
      collagen-ADP (C/ADP) were routinely done in all patients. Additional tests,
      bleeding time (BT), and von Willebrand factor (vWF: Ag) were performed only in
      patients with a positive bleeding history and/or evidence of impaired hemostasis;
      e.g., drug ingestion. The bleeding history was negative in 5021 patients (88.8%)
      but positive in the remaining 628 (11.2%). Impaired hemostasis could be verified
      only in 256 (40.8%) of these patients. The vast majority were identified with PFA
      100: C/E (n=250; 97.7%). The other six patients with impaired hemostasis were
      identifiable solely based on the PT (n=2), PFA-100: C/ADP (n=2), and vWF: Ag
      (n=2). The PFA-100: C/ADP detected 199 patients (77.7%). The only abnormality
      found among patients with a negative bleeding history was a prolonged aPTT due to
      lupus anticoagulant in nine patients (0.2%). The sensitivity of the PFA-100:
      collagen-epinephrine was the highest (90.8%) in comparison to the other screening
      tests (BT, aPTT, PT, vWF: Ag). The positive predictive value of the PFA-100:
      collagen-epinephrine was high (81.8%), but the negative predictive value was
      higher (93.4%). The use of a standardized questionnaire and, if indicated, the
      PFA-100: C/E and/or other specific tests not only ensure the detection of
      impaired hemostasis in almost every case but also a significant reduction of the
      cost.

PMID- 15247977
TI  - Activated platelet and oxidized LDL induce endothelial membrane vesiculation:
      clinical significance of endothelial cell-derived microparticles in patients with
      type 2 diabetes.
AB  - Endothelial cells, platelets, and oxidized LDL could play very important roles in
      the development of atherosclerosis in diabetes patients. The levels of plasma
      endothelial cell-derived microparticles (EDMP), platelet-derived microparticles
      (PDMP), platelet-P-selectin (plt-PS), soluble CD40 ligand (sCD40L), and anti
      oxidized LDL antibody were measured and compared to develop a better
      understanding of their potential contribution to diabetic vascular complications.
      The concentrations of EDMP, PDMP, plt-PS, and sCD40L in diabetic patients were
      significantly higher than those in normal subjects. The number of EDMPs in
      patients with diabetes complicated by nephropathy was significantly higher than
      that in those without complications. Levels of anti-oxidized LDL antibody were
      also higher in type 2 diabetic patients than in control subjects. In addition,
      anti-oxidized LDL antibody levels correlated with EDMP, PDMP, plt-PS, and sCD40L
      levels in nephropathy patients. In the nephropathy group treated with
      sarpogrelate hydrochrolide, a 5-HT(2A) receptor antagonist, EDMP, PDMP, plt-PS,
      and sCD40L levels were decreased significantly. Oxidized LDL increased expression
      of plt-PS, and also promoted shedding of PDMP. Furthermore, oxidized LDL promoted
      a dose-dependent release of 5-hydroxytriptamine. On the other hand, activated
      platelets and PDMP promoted endothelial cells and THP-1 (monocytic cell line)
      interaction, and membrane vesiculation occurred in the presence of oxidized LDL.
      These findings suggest that activated platelets and oxidized LDL induce EDMP
      generation, and that elevated EDMPs may be a sign of vascular complications in
      type 2 diabetic patients, particularly those who suffer from diabetes-associated
      nephropathy.

PMID- 15247978
TI  - Age-dependent likelihood of in situ thrombosis in secondary pulmonary
      hypertension.
AB  - Pulmonary arterial thrombosis (PAT) may complicate the clinical course of
      pulmonary hypertension associated with congenital heart disease (so-called
      Eisenmenger syndrome, ES). In this study, variables were sought that could
      represent risk factors for the occurrence of this complication. Twenty patients
      aged 11 to 53 (median, 33) years were studied. The presence of PAT (spiral
      computed tomography angiography) was correlated with age, gender group, PAP,
      hematocrit, peripheral oxygen saturation (SpO(2)), and plasma levels of
      endothelial and coagulation dysfunction markers: von Willebrand factor antigen
      (vWF:Ag), tissue plasminogen activator (t-PA), and D-dimer (enzyme immunoassay).
      Patients were classified according to the presence (group 1, N=7), or absence
      (group 2, N=13) of PAT. Group 1 patients were older (42+/-8 vs. 27+/-10 years in
      group 2, p=0.0051), had lower SpO(2) (82+/-7% vs. 89+/-6% in group 2, p=0.0462)
      and increased D-dimer levels (637 vs. 149 ng/mL in group 2, median values,
      p=0.0235). A trend was observed toward an increase in vWF:Ag (125+/-29 vs. 103+/
      18 U/dL in group 2, p=0.0789) and t-PA (15.7 vs. 9.4 ng/mL in group 2, median
      values, p=0.0689). Age was the main variable influencing the occurrence of PAT in
      multivariate analysis (p=0.0026), with odds ratio of 1.204 per year. The age of
      35 years was 86% sensitive and 85% specific for occurrence of PAT. Age correlated
      positively with t-PA (r=0.57, p=0.0111). Thus, PAT is highly prevalent in ES as
      an age-dependent event, probably associated with endothelial dysfunction.
      Prophylactic anticoagulation should be considered before the age of 30 years, in
      particular in subjects with low SpO(2) and increased D-dimer levels.

PMID- 15247979
TI  - Erythropoietin-induced thrombosis as a result of increased inflammation and
      thrombin activatable fibrinolytic inhibitor.
AB  - Chronic inflammation is a major cause of morbidity and mortality in end-stage
      renal disease. The associated anemia in these patients due to renal cortical
      atrophy and erythropoietin deficiency is treated with recombinant erythropoietin.
      Recent reports suggest a growing incidence of symptomatic venous thrombosis in
      cancer patients treated with recombinant erythropoietin. Several investigators
      have reported on different mechanisms of thrombosis in these patients. We
      hypothesize that thrombosis in patients with end-stage renal disease due to
      increased expression of C-reactive protein (CRP) as a result of chronic
      inflammation promotes the release of thrombin activatable fibrinolytic inhibitor
      causing fibrinolytic deficit and eventually thrombosis. Furthermore, because
      endothelial nitric oxide is responsible for the maintenance of the normal
      vascular function, the decreased levels of nitric oxide in chronic inflammation
      cause endothelial damage and result in thrombosis. To test this hypothesis, blood
      samples were collected from 106 patients (49 male and 57 female, aged 59.8+/-15.7
      years) with end-stage renal disease undergoing hemodialysis and treated with
      recombinant erythropoietin at a mean dose of 201.8 U/kg/week. Blood samples were
      drawn in 5-mL tubes containing 3.2% sodium citrate just before the hemodialysis
      procedure. These blood samples were immediately centrifuged to obtain platelet
      poor plasma, which was aliquoted and frozen at -70 degrees C until further
      analysis. Erytropoietin antibodies were measured using an anti-EPO enzyme-linked
      immunosorbent assay (ELISA) method developed in our laboratory. Nitric oxide was
      measured using a NO analyzer (Sievers 280I, Ionics, Boulder, CO). Plasma CRP
      levels were measured with a highly sensitive ELISA method IMUNOCLONE CRP ELISA
      (American Diagnostica, Greenwich, CT). TAFI antigen levels in plasma were
      analyzed with an IMUCLONE TAFI ELISA kit (American Diagnostica, Greenwich, CT).
      TAFI functional activity was assayed with an ACTICHROME TAFI activity kit. The
      measured levels of nitric oxide, CRP, TAFI antigen, and TAFI functional were
      37.36+/-36.8 (normal value, 37.49+/-18.96; range, 19.3-102 microM), 12.27+/-10.6
      (normal value, < 1 microg/mL), 146.9+/-28.4% NHP (normal, 100% NHP), and 102.55+/
      37% NHP (normal range, 22.3-165.7; mean, 89.5% NHP), respectively. The
      erythropoietin antibody was detected in 9.4% of the patient group. While 20% of
      the erythropoietin antibody-positive and 27.1% of the erythropoietin antibody
      negative patients experienced chest pain, thrombotic events developed in 9.4% of
      the erythropoietin antibody-negative patients. These data provide the rationale
      for a novel mechanism of thrombosis through increased activity of CRP, nitric
      oxide, and TAFI, leading to fibrinolytic deficit and thrombosis in patients
      treated with erythropoietin.

PMID- 15247980
TI  - Factor V Leiden and prothrombin G20210A mutations and the risk of
      atherothrombotic events in systemic lupus erythematosus.
AB  - Because genetic predisposition to atherothrombosis in systemic lupus
      erythematosus (SLE) remains to be determined, the most common genetic
      prothrombotic factors, prothrombin G20210A and factor V Leiden mutations, were
      studied. Seventy-four SLE patients with vascular ischemia (SLE cases) were
      studied and stratified into myocardial infarction and/or cerebrovascular accident
      subgroup (MI/CVA), and coronary heart disease subgroup without overt arterial
      thrombotic events (CHD). Seventy-one SLE patients without atherothrombosis were
      investigated as SLE controls. Factor V Leiden was detected in six cases (five in
      MI/CVA, one in CHD group) and three controls (OR 2.00, 95%CI 0.48-8.32). Two
      cases (both CHD patients) had prothrombin G20210A mutation vs. three controls (OR
      0.63, 95%CI 0.1-3.88). Anticardiolipin antibodies (aCL) were increased in cases
      vs. controls (39/74 vs. 27/71); however, this was not statistically significant
      (OR 1.82, 95%CI 0.94-3.52). Neither univariate nor multivariate analysis
      indicated that investigated mutations are risk factors for atherothrombosis in
      SLE cases, MI/CVA, or CHD subgroups. Overall, disease activity was the strongest
      risk factor for atherothrombosis (p=0.0014) in SLE cases. Combination of disease
      activity+gender was the best predictor of atherothrombotic process (p=0.00045) in
      this cohort. In MI/CVA subgroup, disease activity was the only predictor
      (p=0.0058). In CHD patients, the best predictive value was conferred by
      combination of hypertension+gender+disease activity (p=0.00077). No other
      investigated risk factor (including aCL) conferred an increased risk individually
      or potentiated the other risk factors. The results deny the role of investigated
      mutations in atherothrombosis in SLE, but they underscore the importance of
      disease activity (i.e., ongoing inflammation) in pathogenesis of atherosclerosis
      and arterial thrombosis.

PMID- 15247981
TI  - Monitoring of rheologic variables during postoperative high-dose brachytherapy
      for uterine cancer.
AB  - Oxygenation of tumor tissue has recently been assed an important prerequisite for
      the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common
      phenomenon in malignancy and a cause of reduced oxygen transport capacity that
      would favour tissue hypoxia. Hemorheological variables were serially tested
      preoperatively, during four cycles of fractionated adjuvant IR(192) HDR after
      loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months
      postoperatively in patients with cervical (n=12) and endometrial cancer (n=26).
      Women who were scheduled for benign tumor surgery served as controls (n=29).
      Preoperatively, in cervical and endometrial cancer patients, mean plasma
      viscosity (PV: 1.31+/-0.1 mPa s; p<0.05; 1.35+/-0.13 mPa s; p<0.001) and
      fibrinogen levels (383+/-46 mg/dL; p<0.05; 379+/-117 mg/dL; p<0.05) were higher
      as compared to the controls (1.25+/-0.07 mPa s; 314+/-89 mg/dL). Red blood cell
      aggregation at low shear and stasis (RBC agg.: 15.7+/-5.6; p<0.05; 29.6+/-9.1;
      p<0.05) was higher in endometrial cancer patients as compared to the controls
      (13.7+/-3.4; 25.3+/-5.6). Postoperatively PV decreased in endometrial cancer
      patients and transiently increased in cervical cancer patients. After the third
      session of irradiation in both cancer groups, PV regained and at the 6-month
      checkup, levels were higher as compared to the values before surgery.
      Postoperatively fibrinogen levels increased and remained higher throughout HDR-AL
      and 6 months postoperatively. After surgery and during irradiation, anemia
      persisted in both cancer groups while hematocrit recovered after 6 months in
      endometrial cancer patients. Thrombosis was diagnosed in three patients
      postoperatively (7.9 %) but in none during HDR-AL. While a temporary reduction of
      hyperviscosity is found postoperatively and during HDR-AL in uterine cancer
      patients, 6 months after surgery RBC aggregation, PV, and hematocrit returned to
      the pretreatment range.

PMID- 15247982
TI  - Studies on the effect of calcium in interactions between heparin and heparin
      cofactor II using surface plasmon resonance.
AB  - Heparin is the most acidic polysaccharide in the human body and as a result
      interacts with many cationic species, including ions and proteins, giving rise to
      myriad biologic activities. Heparin cofactor II (HCII) is a serine protease
      inhibitor that resembles antithrombin (ATIII) in its ability to be activated by
      heparin. The interaction of heparin with HCII has been the focus of many studies
      using affinity chromatography and fluorescence spectroscopy. In this study,
      surface plasmon resonance (SPR) spectroscopy was used to quantitatively measure
      the interaction of heparin and HCII using a heparin biochip prepared by
      covalently immobilizing preformed albumin-heparin conjugate. HCII contains
      multiple EF hand domains that represent putative calcium ion binding sites. The
      interactions of HCII with heparin, low-molecular-weight heparin, and heparin
      oligosaccharides (disaccharide, tetrasaccharide, hexasaccharide) were examined in
      solution competition experiments using SPR. The results also showed while calcium
      ions enhanced the heparin/HCII interaction, the activity of heparin-HCII complex
      against thrombin was not calcium dependent but can be enhanced by the presence of
      calcium.

PMID- 15247984
TI  - The predictability of factor V Leiden (FV:Q(506)) gene mutation via clotting
      based diagnosis of activated protein C resistance.
AB  - After the discovery of activated protein C resistance (APCR) due to factor V
      Leiden mutation and the causal relationship of the phenomenon with clinical
      thromboembolism, a wide variety of functional clotting-based assays were
      developed for testing of APCR in relation to the specific DNA-based analysis of
      FV:Q(506) Leiden. The aim of this study is to assess a clotting-based APCR assay
      using procoagulant crotalidae snake venom with respect to the sensitivity,
      specificity, and predictability for the presence of the factor V Leiden mutation.
      APCR testing and factor V DNA analyses have been performed concurrently on 319
      patient specimens. APCR values of the patients with homozygous factor V Leiden
      mutation (70.4+/-13.5 s) were significantly lower (p<0.001) in comparison to the
      subjects with the heterozygous mutation (87.6+/-13.4 s). The assay is highly
      sensitive (98.7%) and specific (91.9%) for the screening of factor V Leiden
      mutation. The sensitivity and specificity of the APCR testing reached to 100%
      below the cut-off value of 120 s among the patients with homozygous factor V
      Leiden mutation. Therefore, this method could help the desired effective optimal
      screening strategy for the laboratory search of hereditary thrombophilia focusing
      on the diagnosis of APCR due to FV:Q(506).

PMID- 15247983
TI  - Effect of age on oral contraceptive-induced venous thrombosis.
AB  - This study was undertaken to investigate the effect of age on oral contraceptive
      induced venous thrombosis. All women seen in the University of Padua Department
      of Medical and Surgical Science who had had two courses of oral contraceptive
      therapy at different ages were included. A total of 28 subjects met these
      criteria. Fifteen patients had a congenital or acquired prothrombotic condition,
      whereas 13 women were normal subjects. The mean age at which thrombosis occurred
      was 33.3 and 36.3 years for women with or without a prothrombotic condition,
      respectively. The ages during which the women remained asymptomatic were 23.1 and
      23.3 years for women with or without a predisposing defect, respectively.
      Thrombosis occurred, during the second course of oral contraceptive therapy,
      after the mean duration of 6.5 cycles or 18.4 cycles in women with or without
      prothrombotic defects, respectively. During the asymptomatic course,
      approximately the same number of women took old progestins or third-generation
      compounds. On the contrary, during the second period, 21 of 28 women took
      progestins with third-generation compounds. Age seems to plays an important role
      in oral contraceptive-induced venous thrombosis. In normal women, thrombosis
      occurred after a greater number of oral contraceptive cycles as compared with the
      women with prothrombotic defects. Because the majority of women took preparations
      that contained third-generation progestins during the second course of therapy,
      concomitant contributing effects of these compounds cannot be excluded.

PMID- 15247985
TI  - Is the circulating urokinase plasminogen activator upregulated by the circulating
      p105 fraction of the HER-2/neu proto-oncogene in patients with cervical cancer?
AB  - It has been suggested that urokinase plasminogen activator (uPA) in cancer cells
      is upregulated by the p185 kD form of the HER-2/neu oncogene. This study was
      performed to see if the extracellular domain of HER-2/neu, the p105 fraction,
      which is found in the circulation, has any regulatory influence on uPA in
      patients with cervical cancer. Levels of uPA and p105 HER-2/neu were determined
      in blood from age-matched controls and patients with early and advanced cervical
      cancer. In the patients with cervical cancer, samples were obtained before
      treatment only. No significant increase in either uPA or HER-2/neu was seen in
      the patients before their treatment for cervical cancer. Additionally,
      correlation analysis of circulating uPA and HER-2/neu against each other in both
      the controls and cervical cancer indicated no relationship except in early stage
      disease. It appears that circulating uPA and HER-2/neu are not altered in
      patients with cervical cancer, either early or advanced stages. The upregulation
      of uPA by HER-2/neu seen in cancer cells in vitro appears to occur in vivo in
      early stage cervical cancer.

PMID- 15247986
TI  - Thrombosis and a hypercoagulable state in HIV-infected patients.
AB  - Human immunodeficiency virus infection is an illness with protean manifestations
      including hematological abnormalities. Thromboembolic complications in HIV
      infected patients have been described. Recent literature describes an incidence
      ranging from 0.26% to 7.6%; higher incidence is seen in patients with active
      opportunistic infections or malignancy, and in patients with the acquired
      immunodeficiency syndrome. A variety of potential mechanisms have been proposed
      to account for the observed hypercoagulability in HIV-infected patients. These
      include the presence of antiphospholipid-anticardiolipin antibodies, decreased
      activities of natural anticoagulants (especially protein S), and increased
      platelet activation. Recent epidemiological studies emphasize the increased
      incidence of thromboembolic events including myocardial infarction in the HIV
      infected population after the introduction of highly active antiretroviral
      therapy. The use of protease inhibitors in particular is implicated. A
      hypercoagulable state and especially thromboses are emerging as clinical issues
      in HIV-infected patients. Further studies are in order to more clearly delineate
      the pathophysiologic mechanism(s) of thromboses in HIV-infected patients.

PMID- 15247987
TI  - Blood carboxyhemoglobin level and platelets: a correlation study.
AB  - The high level of air pollution is an important problem. One of these major
      pollutants is carbon monoxide (CO), which can block normal physiology.
      Hematologic alteration is another important side effect of exposure to CO.
      Adverse effects on red blood cells, formation of nonfunctional hemoglobin called
      carboxyhemoglobin (COHb), have been well documented. The effect of CO on
      platelets is not well documented. Therefore, the correlation between the level of
      blood COHb and the platelet count was evaluated in 28 subjects exposed to CO.
      There is no statistical significance; however, decreased platelet count, platelet
      distribution width, and plateletcrit, and an increase in blood COHb were
      observed.

PMID- 15247988
TI  - Platelet count and platelet parameters in hemoglobin E carriers.
AB  - Hemoglobinopathies are an important inherited disorder with a high prevalence in
      Thailand. Of several hemoglobinopathies, hemoglobin E (Hb) disorder (beta 26, GAG
      AAG, Glu-Lys) is the most common. Coagulation disorders in these patients have
      also been proposed. Even though thrombotic risks in the patients with hemoglobin
      disorders from standpoints of platelet dysfunction and coagulation factors are
      controversial, they are in favor of thrombosis due to thrombocytosis. A study was
      performed in 57 healthy subjects to evaluate platelet count and platelet
      parameters in hemoglobin E carriers compared to values in healthy subjects.
      Classified by standard hemoglobin electrophoresis, there were 46 healthy subjects
      and 11 hemoglobin E carriers. There are no significant differences in platelet
      count and platelet parameters between the two groups (p > 0.05). Although there
      are reports that indicate the change in the quality of platelet in hemoglobin E
      disorders, no quantitative disorder was detected. There was no trend toward
      increased platelet count in the HbE carriers.

PMID- 15247989
TI  - Effect of smoking on platelet count and platelet parameters: an observation.
AB  - Arterial thrombosis occurs with increased frequency in cigarette smokers. It is
      believed that disturbance of platelet function, especially aggregation, is the
      essential mechanism responsible for this pathology. However, the effect of
      smoking on the quantity of platelets might be another contributing factor. The
      effect of smoking on platelet count is still controversial. We performed a cross
      section-al study to compare the platelet count and platelet parameters in Thai
      police who are smokers and non-smokers. A total of 30 Thai police in Bangkok were
      included in this study. Of the 30 police, there are 5 non-smokers and 25 smokers.
      The platelet counts and platelet parameters of the subjects were not
      significantly different between smokers and non-smokers.

PMID- 15247990
TI  - A life-threatening second trimester disseminated intravascular coagulopathy with
      protein s deficiency.
AB  - Disseminated intravascular coagulopathy (DIC) is an uncommon but serious
      complication of pregnancy. Placental abruption is the most common associated
      condition among the causes of acute obstetrical DIC. We present a case of life
      threatening DIC complicating placental abruption in the second trimester of
      pregnancy with protein S deficiency as a triggering factor, which necessitated
      urgent termination of pregnancy.

PMID- 15247991
TI  - Menorrhagia due to a qualitative deficiency of plasminogen activator inhibitor-1:
      case report and literature review.
AB  - A case is presented of a 26-year-old woman who was referred to the hematology
      clinic because of her report of a family history of plasminogen activator
      inhibitor-1 (PAI-1) deficiency. Since menarche, she had suffered from severe
      menorrhagia, but she had assumed that this was unrelated to her mother's history
      of repeated life-threatening bleeding. Her menorraghia was evident by using
      greater than 100 pads per period, bleeding as long as 4 continuous months, and
      even bleeding through her clothes despite using both tampons and pads. Evaluation
      with pelvic examination, endometrial biopsy, and pelvic ultrasound was
      unremarkable. Medroxyprogesterone acetate treatment for her dysfunctional uterine
      bleeding was unsuccessful. Laboratory evaluation revealed iron deficiency anemia
      but otherwise normal platelets, bleeding time, prothrombin time, activated
      partial thromboplastin time, and vonWillebrand's studies. Despite any
      preconceptions, examination for a fibrinolytic defect ultimately demonstrated a
      PAI-1 antigen level of 11.4 ng/mL (4.0-43 ng/mL) and PAI-1 activity less than 5
      AU/mL (5-37 AU/mL) and clinically supported a diagnosis of a hereditary,
      qualitative PAI-1 defect. She was treated with aminocaproic acid with return to
      relatively normal menses. Future treatment should also prevent excessive bleeding
      during trauma, surgery, or childbirth. Further evaluation of this patient and her
      family is planned and may help elucidate the important role of PAI-1 in the
      complicated balance between hemostasis and hemorrhage.

PMID- 15247992
TI  - Serum salicylate level in Thai elderly.

PMID- 15247995
TI  - Monitoring the electroencephalogram during bypass procedures.
AB  - Electroencephalographic monitoring has been performed since the early days of
      cardiopulmonary bypass. Despite this long experience, the technology has never
      been widely used for cardiac operations. This review examines the reasons for the
      limited use and describes technological advances that may alter this pattern.

PMID- 15247996
TI  - Human auditory evoked potentials in the assessment of brain function during major
      cardiovascular surgery.
AB  - Focal neurologic and intellectual deficits or memory problems are relatively
      frequent after cardiac surgery. These complications have been associated with
      cerebral hypoperfusion, embolization, and inflammation that occur during or after
      surgery. Auditory evoked potentials, a neurophysiologic technique that evaluates
      the function of neural structures from the auditory nerve to the cortex, provide
      useful information about the functional status of the brain during major
      cardiovascular procedures. Skepticism regarding the presence of artifacts or
      difficulty in their interpretation has outweighed considerations of its potential
      utility and noninvasiveness. This paper reviews the evidence of their potential
      applications in several aspects of the management of cardiac surgery patients.
      The sensitivity of auditory evoked potentials to the effects of changes in brain
      temperature makes them useful for monitoring cerebral hypothermia and rewarming
      during cardiopulmonary bypass. The close relationship between evoked potential
      waveforms and specific anatomic structures facilitates the assessment of the
      functional integrity of the central nervous system in cardiac surgery patients.
      This feature may also be relevant in the management of critical patients under
      sedation and coma or in the evaluation of their prognosis during critical care.
      Their objectivity, reproducibility, and relative insensitivity to learning
      effects make auditory evoked potentials attractive for the cognitive assessment
      of cardiac surgery patients. From a clinical perspective, auditory evoked
      potentials represent an additional window for the study of underlying cerebral
      processes in healthy and diseased patients. From a research standpoint, this
      technology offers opportunities for a better understanding of the particular
      cerebral deficits associated with patients who are undergoing major
      cardiovascular procedures.

PMID- 15247997
TI  - Evoked potentials during cardiac and major vascular operations.
AB  - Somatosensory evoked potentials are widely used in spine surgery to prevent
      injury to the spinal cord. However, their application in cardiac and major
      vascular surgery is largely unappreciated. This paper will review the unique
      stresses placed on peripheral nerves, spinal cord, and brain during these
      operations. In addition, the potential benefits of peri-operative somatosensory
      evoked potentials monitoring are described in detail.

PMID- 15247993
TI  - Trends in cochlear implants.
AB  - More than 60,000 people worldwide use cochlear implants as a means to restore
      functional hearing. Although individual performance variability is still high, an
      average implant user can talk on the phone in a quiet environment. Cochlear
      implant research has also matured as a field, as evidenced by the exponential
      growth in both the patient population and scientific publication. The present
      report examines current issues related to audiologic, clinical, engineering,
      anatomic, and physiologic aspects of cochlear implants, focusing on their
      psychophysical, speech, music, and cognitive performance. This report also
      forecasts clinical and research trends related to presurgical evaluation, fitting
      protocols, signal processing, and postsurgical rehabilitation in cochlear
      implants. Finally, a future landscape in amplification is presented that requires
      a unique, yet complementary, contribution from hearing aids, middle ear implants,
      and cochlear implants to achieve a total solution to the entire spectrum of
      hearing loss treatment and management.

PMID- 15247998
TI  - Electrophysiologic monitoring during surgery to repair the thoracoabdominal
      aorta.
AB  - The repair of aneurysms and dissections that involve the thoracoabdominal aorta
      represent a major stress to the cardiovascular surgery team because of the feared
      complication of paraplegia. Here, the etiology of this complication is explained
      through a description of the relevant surgical anatomy and characteristics of
      hemodynamic support. In addition, recent advances in the neurophysiologic
      assessment of the descending motor pathways and their application to
      perioperative monitoring are discussed.

PMID- 15247999
TI  - Intraoperative transcranial ultrasonic monitoring for cardiac and vascular
      surgery.
AB  - The brain is the only organ not routinely monitored by any direct method during
      the administration of anesthesia. Anesthesiologists rely primarily on indirect
      physiologic evidence provided by blood pressure, peripheral pulse oximetry, heart
      rate, and respiratory and anesthetic gas concentrations to determine that brain
      blood flow and oxygenation are adequate. The reasons for this practice are that:
      (1) after millions of anesthetics significant numbers of adverse neurologic
      outcomes have not occurred, (2) the interpretation of transcranial Doppler,
      electroencephalogram, and near-infrared cerebral oximetry requires experienced
      personnel, and (3) the evidence of cost-benefit to support monitoring is limited.
      Brain monitoring generally has been confined to procedures where the brain is
      exposed to unique insults and risks specific to the procedures and where reliance
      on indirect physiologic evidence of cerebral integrity has been proven to be
      unreliable. Transcranial Doppler monitoring is valuable in the assessment of
      established surgical techniques, refinement of recent surgical techniques, and
      development of new techniques and instrumentation. Brain monitoring with
      transcranial Doppler is of particular value when deviations from established
      surgical or anesthetic techniques may place the brain at risk for cerebral hyper-
      or hypoperfusion, gaseous or particulate embolization, or their combined effects.
      This paper discusses applications of transcranial Doppler in coronary artery
      bypass surgery, aortic arch procedures, pediatric cardiac surgery, carotid
      endarterectomy, and a few other special cases. The insight into cerebral
      physiology is unique to the continuous window on the brain that transcranial
      Doppler provides.

PMID- 15248000
TI  - Cerebral oximetry for cardiac and vascular surgery.
AB  - The technology of transcranial near-infrared spectroscopy (NIRS) for the
      measurement of cerebral oxygen balance was introduced 25 years ago. Until very
      recently, there has been only occasional interest in its use during surgical
      monitoring. Now, however, substantial technologic advances and numerous clinical
      studies have, at least partly, succeeded in overcoming long-standing and
      widespread misunderstanding and skepticism regarding its value. Our goals are to
      clarify common misconceptions about near-infrared spectroscopy and acquaint the
      reader with the substantial literature that now supports cerebral oximetric
      monitoring in cardiac and major vascular surgery.

PMID- 15248001
TI  - Perioperative multimodality neuromonitoring: an overview.
AB  - Neurologic damage after cardiac surgery remains an important cause of
      postoperative morbidity. In addition to a wide variety of procedural risks,
      patient-specific factors such as the presence of extracranial or intracranial
      atherosclerotic disease, either alone or together, have a fundamental impact on
      the risk of brain injury developing after cardiovascular surgery. A variety of
      neurophysiologic monitoring techniques have been used during cardiovascular
      surgery in hopes of averting neurologic injury. In this issue of Seminars, the
      strengths and weaknesses of each are discussed by a group of highly experienced
      clinical investigators. The ultrasound techniques of epiaortic scanning and
      continuous transcranial Doppler insonation of large intracranial arteries can
      alter perfusion management and surgical habits to markedly decrease the delivery
      of atherosclerotic, lipoidal, and gaseous microemboli to the brain and other
      vital organs. Cerebral hypoperfusion from unrecognized cerebral venous
      obstruction, inadequate mean arterial pressure, or hypocapnic cerebral alkalosis
      can be identified by transcranial near-infrared spectroscopy,
      electroencephalogram, and sensory evoked potentials. Compromise of spinal cord
      perfusion during the repair of thoracoabdominal aneurysms may be identified and
      corrected with the guidance provided by transcranial electric motor-evoked
      potentials. Quantitative electroencephalogram and auditory evoked potential
      indices also appear beneficial in producing objective measures of the hypnotic
      component of anesthesia. These neuromonitoring methods, particularly when used in
      concert, can improve overall patient outcome and reduce hospital length of stay.

PMID- 15248002
TI  - Importance of new combination vaccines.

PMID- 15248003
TI  - Education for community pediatrics.

PMID- 15248004
TI  - Economic considerations associated with Pediculus humanus capitis infestation.
AB  - An estimated 6 to 12 million head lice infestations occur in the United States
      annually, with children ages 3 to 12 most likely to be affected. There are
      significant direct costs associated with treatment and indirect costs due to lost
      time from school. Anecdotal reports suggest that direct costs of treatment are in
      the hundreds of millions of dollars annually. Indirect costs are also substantial
      but more difficult to quantify. Examples of indirect costs include missed days
      from schools that use a "no nit" policy, lost wages for parents who must stay
      home with children, and costs of daycare for parents who cannot miss work.
      Contributors to the expense of treating head lice include misdiagnosis, and,
      consequently unneeded treatment; treatment failure due to misuse of pediculicides
      or other agents; and developing resistance, particularly to over-the-counter
      pyrethroid agents. An overview of direct and indirect costs of infestation are
      included in this review, along with a discussion of factors that lead to misuse
      and overuse of pediculicides. More accurate diagnosis of head lice infestation
      may provide the most effective means of controlling the costs of care and
      ensuring proper use of pediculicides.

PMID- 15248005
TI  - The effect of montelukast sodium on the duration of effusion of otitis media.
AB  - This study tests the hypothesis that montelukast sodium, a selective leukotriene
      receptor antagonist, will decrease the duration of the effusion of otitis media.
      Tympanometry and spectral gradient acoustic reflectometry were used to confirm
      the effusion of otitis media in patients between 2 and 12 years of age. Patients
      were treated with amoxicillin for 10 days and montelukast sodium or placebo for
      30 days in a random, double-blind manner. Sixty patients completed the study: 31
      received placebo and 29 received montelukast sodium. At a 4-week follow-up visit,
      5 ears (16%) were free of effusion in the placebo group and 17 (58%) in the
      montelukast sodium group. The difference was significant. The efficacy of
      montelukast sodium in clearing the effusion was 49%.

PMID- 15248006
TI  - Is late bottle-weaning associated with overweight in young children? Analysis of
      NHANES III data.
AB  - To determine whether age of bottle-weaning is associated with overweight in young
      children, National Health and Nutrition Examination Survey III data for 3027
      children aged 3-5 years were analyzed. The main outcome measure, the child's body
      mass index (BMI), was measured as: <85%, 85-95%, >95%. Mean bottle-weaning age
      was 18.78 months. After adjustment for potential confounders, each additional
      month of bottle use corresponded to a 3% increase in the odds of being in a
      higher BMI category (95% CI 0.0099-0.0535). Prolonged bottle use in young
      children is associated with increased risk of overweight. From a preventive
      medicine standpoint, decreasing exposure to this potential risk for childhood
      overweight is indicated.

PMID- 15248007
TI  - Parental beliefs and practices regarding early introduction of solid foods to
      their children.
AB  - This study was a cross-sectional survey of primary female caregivers during their
      child's 4-month well-child visit. Our objectives were to document current
      caregiver awareness of infant feeding guidelines, and calculate the frequency of
      and reasons for early introduction of solid foods. Questionnaires were completed
      for 102 children. Forty-five respondents (44%) introduced solids at less than 4
      months of age. Hispanic caregivers, OR 0.2 (0.07-0.9), and those who breastfed
      (partial or exclusive), OR 0.4 (0.2-0.9), were less likely to introduce cereal at
      less than 4 months of age. Among caregivers who introduced solids at less than 4
      months, 36 (80%) stated that the child was not satisfied with formula or breast
      milk alone and 24 (53%) stated that solids helped the child sleep better at
      night. Thirty-four caregivers (76%) who started solids at less than 4 months were
      aware of guidelines regarding proper infant feeding practices. Despite knowledge
      of infant feeding guidelines, female caregivers frequently introduce solids at
      less than 4 months of age. Early targeted anticipatory guidance is needed to
      address the most common reasons caregivers begin solid foods before the
      recommended age.

PMID- 15248008
TI  - Retrospective assessment of subacute or chronic osteomyelitis in children and
      young adults.
AB  - To identify factors associated with and to describe treatment outcomes of
      pediatric subacute or chronic osteomyelitis (S/CO), we retrospectively identified
      52 patients with S/CO from January 1994 to November 1999 seen at a large
      pediatric hospital infectious disease clinic. S/CO was defined by the following:
      >10 days of clinical symptoms; radiographic, surgical, or pathologic changes
      consistent with S/CO; or relapse of prior osteomyelitis. Of these patients 63%
      were male, median age 9 years. Bones involved included vertebra (19% of
      subjects), femur (17%), finger (12%), humerus (10%), and tibia (8%). Sixty-five
      percent had at least 1 risk factor (most commonly hardware, neurologic disease or
      preceding trauma, sepsis, or surgery). Blood, bone, or wound aspirate cultures
      were positive in 67%, most commonly for Staphylococcus aureus. Erythrocyte
      sedimentation rate (ESR) was elevated in 88% of 41 patients at the time of
      diagnosis. Intravenous antibiotics were given for a median of 6 weeks and oral
      antibiotics for a median of 4.5 months. One child had a complication. In
      conclusion, consideration of S/CO should be high when predisposing factors are
      present. ESR may be useful for determining effectiveness and duration of therapy.
      With prolonged antibiotic therapy nearly all patients demonstrated resolution of
      disease.

PMID- 15248009
TI  - Seizure disorder as a risk factor for gastroesophageal reflux in children with
      neurodevelopmental disabilities.
AB  - The proportion of children with severe neurodevelopmental disabilities, in whom
      symptoms of gastroesophageal reflux develop after gastrostomy placement, has not
      been well studied. The medical records of children who received a gastrostomy
      tube (with or without a simultaneous antireflux procedure) at our institution
      between 1987 and 1997 were reviewed to identify neurologically related diagnoses
      at the time of the gastrostomy, diagnostic tests ordered to detect reflux, and
      dates and reasons for re-admissions within 2 years of discharge. Of 102 patients
      studied, 37 received a gastrostomy tube alone. Complete follow-up data were
      available for 30 of these patients, 7 of whom (23%) required subsequent
      antireflux surgery within 2 years. Patients with a seizure disorder had greater
      than a 4-fold risk of re-admission for this operation compared with other
      patients (57% [4/7] vs. 13% [3/23]; P=0.03). In a child with severe
      neurodevelopmental disability, the existence of a seizure disorder at the time of
      a gastrostomy operation increases the risk of subsequently requiring an
      antireflux procedure by a factor of 4.

PMID- 15248010
TI  - Long-term sequelae of lightning strike in a child: a case report and review.

PMID- 15248011
TI  - Yellow nail syndrome in an infant presenting with lymphedema of the eyelids and
      pleural effusion.

PMID- 15248012
TI  - Trends in major types of poisoning exposures in children reported to a regional
      poison control center, 1994-2001.

PMID- 15248013
TI  - Lactobezoar: a case report.

PMID- 15248014
TI  - Early onset of neonatal Streptococcus pneumoniae bacteremia and septic arthritis.

PMID- 15248015
TI  - Suspected abuse.

PMID- 15248016
TI  - A sallow infant.

PMID- 15248018
TI  - Inositol and phosphatidylinositol mediated mediated glucose derepression, gene
      expression and invertase secretion in yeasts.
AB  - Glucose repression occurs in many yeast species and some filamentous fungi, and
      it represses the expression and secretion of many intracellular and extracellular
      proteins. In recent years, it has been found that many biochemical reactions in
      yeast cells are mediated by phosphatidylinositol (PI)-type signaling pathway.
      However, little is known about the relationships between PI-type signaling and
      glucose repression, gene expression and invertase secretion in yeasts. Many
      evidences in our previous studies showed that glucose repression, invertase
      secretion, gene expression and cell growth were mediated by inositol and PI in
      Saccharomyces and Schizosaccharomyces. The elucidation of the new regulatory
      mechanisms of protein secretion, gene expression and glucose repression would be
      an entirely new aspect of inositol and PI-type signaling regulation in yeasts.

PMID- 15248019
TI  - A human t-PA mutant cDNA cassette knocked in the murine fgfr-4 locus targeting
      for mammary gland expression.
AB  - The expression of foreign gene in transgenic animals produced by pronuclear
      microinjection is often confounded by the position effects caused by not only the
      nature of chromosomal integration site but also the number and arrangement of
      multiple transgene copies. Gene targeting provides a new way to overcome these
      inhibitions by introducing single-copy transgene into a chosen site. The choice
      of a good chromosomal site will favor transgene expression in a predictable
      fashion. In this study, we tested a new site (fgfr-4) for foreign gene
      integration and expression. A t-PA mutant (t-PAm) expression cassette under
      bovine alphas1-casein regulatory sequences was efficiently knocked-in fgfr-4 site
      through homologous recombination. The t-PAm was expressed in the milk of all
      targeted mice. Our experiment indicates that the fgfr-4 may be a candidate site
      for knocking foreign gene to make transgenic animals.

PMID- 15248020
TI  - Nucleic acid binding activity of pns6 encoded by genome segment 6 of rice ragged
      stunt oryzavirus.
AB  - The ORF of genome segment 6 (S6) of rice ragged stunt oryzavirus (RRSV)
      Philippines isolate was cloned and sequenced based on the S6 sequence of the
      Thailand isolate. Pns6, the 71 kD product of S6 expressed in E. coli, was
      demonstrated to be a viral non-structural protein of RRSV by Western blotting.
      The gel mobility shift assays showed that Pns6 had nucleic acid binding activity.
      Pns6 could interact with single- and double-stranded forms of DNA and RNA,
      showing a preference for single-stranded nucleic acid and a slight preference for
      RRSV ssRNA over the rice ssRNA, as demonstrated by both competition and
      displacement assays. The binding of Pns6 to nucleic acids is strong and sequence
      non-specific. By using five truncated derivatives of Pns6, it was found that the
      basic region from amino acid 201 to 273 of Pns6 was the unique nucleic acid
      binding domain. Subcellular fractionation of leaf tissues of RRSV-infected rice
      plants and subsequent Western blotting had shown that Pns6 accumulated
      predominately in the cytoplasmic membrane fraction. The possible role of RRSV
      Pns6 in virus replication and assembly is discussed.

PMID- 15248021
TI  - Isolation and partial characterization of a novel pollen-specific cDNA with
      multiple polyadenylation sites from wheat.
AB  - A novel pollen-specific full-length cDNA clone PSG076 was isolated using
      suppression subtractive hybridization and 5'/3' RACE techniques. PSG076 was shown
      to exhibit multi-site polyadenylation by sequencing the 3' ends of the cDNAs. At
      least six transcripts with different length were produced from the single gene
      based on different poly(A) tail attachment sites. However, polyadenylation
      consensus sequence AAUAAA was not seen at the 3'-untranslated sequence. PSG076
      contained a 299 bp 5' untranslated region and an open reading frame of 663 bp
      encoding a 221 amino acid peptide with pI of 4.31. A blast search revealed that
      this sequence did not show a significant similarity to any genes deposited in the
      public database. Southern blot indicated that PSG076 was a single copy gene.
      Northern blot and RT-PCR analysis indicated that PSG076 transcripts showed
      specific expression in mature pollen, and weak or undetectable signals in
      uninucleate microspore, immature seed, stem, young leave, root and ovary. Further
      analysis of the expression pattern in gametophyte showed that PSG076 transcripts
      were undetectable in uninucleate, binucleate microspore and pollen at early
      stage, and were first detectable and increased rapidly at middle and late stages
      of pollen development with the maximum level in mature pollen and also expressed
      in germinating pollen in vivo, suggesting that PSG076 might play a role in pollen
      germination and pollen tube growth in addition to its function in maturation. The
      evidences gathered in this work indicated that the six different transcripts from
      the single gene were differentially expressed during pollen development.

PMID- 15248022
TI  - Cloning, expression and identification of a new trehalose synthase gene from
      Thermobifida fusca genome.
AB  - A new open reading frame in Thermobifida fusca sequenced genome was identified to
      encode a new trehalose synthase, annotated as "glycosidase" in the GenBank
      database, by bioinformatics searching and experimental validation. The gene had a
      length of 1830 bp with about 65% GC content and encoded for a new trehalose
      synthase with 610 amino acids and deduced molecular weight of 66 kD. The high GC
      content seemed not to affect its good expression in E. coli BL21 in which the
      target protein could account for as high as 15% of the total cell proteins. The
      recombinant enzyme showed its optimal activities at 25 degrees and pH 6.5 when it
      converted substrate maltose into trehalose. However it would divert a high
      proportion of its substrate into glucose when the temperature was increased to 37
      degrees, or when the enzyme concentration was high Its activity was not inhibited
      by 5 mM heavy metals such as Cu2+, Mn2+, and Zn2+ but affected by high
      concentration of glucose. Blasting against the database indicated that amino acid
      sequence of this protein had maximal 69% homology with the known trehalose
      synthases, and two highly conserved segments of the protein sequence were
      identified and their possible linkage with functions was discussed.

PMID- 15248023
TI  - A novel gene delivery system targeting urokinase receptor.
AB  - Recombinant proteins that combine different functions required for cell targeting
      and intra-cellular delivery of DNA present an attractive approach for the
      development of nonviral gene delivery vectors. Here, we described a novel protein
      termed ATF-lys10 which facilitated cell-specific gene transfer via receptor
      mediated endocytosis. ATF-lys10 was composed of the amino-terminal fragment of
      urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF
      lys10 protein existed in soluble form, and had antigenicity of human urokinase.
      Purified ATF-lys10 specifically bound to uPAR-expressing cells and formed protein
      DNA complexes with plasmid pGL3-control. After neutralization of excess negative
      charge with poly-L-lysine, these complexes served as a specific gene delivery
      vector for uPAR-expressing cells. Lyso-somotropic compounds, such as chloroquine,
      drastically increased the ATF-lys10 mediated gene delivery efficiency. Our
      results suggest that the recombinant protein ATF-lys10 with the properties of DNA
      binding and tumor cell targeting represents a promising method for gene transfer
      and expression in tumor cells.

PMID- 15248024
TI  - Antitumor effect of a novel adeno-associated virus vector targeting to telomerase
      activity in tumor cells.
AB  - Telomerase activity is a wide tumor marker. Human telomerase reverse
      transcriptase (hTERT), the catalytic subunit of the telomerase, is
      transcriptionally upregulated exclusively in about 90% of cancer cells. In this
      study, we constructed a novel adeno-associated virus (AAV) vector containing the
      human interferon-beta (hIFN-beta) gene under the control of hTERT promoter (AAV
      hTERT-hIFN-beta) and investigated its antitumor effect against various human
      cancer cells in vitro. AAV-hTERT-hIFN-beta displayed cancer-specific hIFN-beta
      expression and cytotoxicity. The cytotoxic ratio was positively correlated with
      the time length of infection. AAV-hTERT-hIFN-beta-mediated apoptotic morphology
      was observed by transmission electron microscopy. Flow cytometry assay also
      revealed that the cytotoxicity of AAV-hTERT-hIFN-beta was mainly an apoptotic
      process. These data indicate that AAV in combination with hTERT-mediated
      therapeutic gene expression may open new possibilities for long-lasting and
      targeting gene therapy of varieties of cancers.

PMID- 15248025
TI  - Identification and characterization of a rat novel gene RSEP4 expressed
      specifically in central nervous system.
AB  - The low-abundantly expressed genes composed the majorities of the mRNAs expressed
      in the central nervous system (CNS), and were thought to be important for the
      normal brain functions. Through differential screening a low-abundance cDNA
      sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI)
      model, we have identified a novel rat gene, rat spinal-cord expression protein 4
      gene (RSEP4). The total length of RSEP4 cDNA is 2006 bp, with a 501 nucleotide
      open reading frame (ORF) that encodes a 167 amino acid polypeptide. Northern blot
      revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization
      showed that the mRNA of RSEP4 was strongly expressed in the CA1, CA2, CA3 and DG
      regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory
      neurons of dorsal horn and large motor neurons of ventral horn of spinal cord.
      Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 293T
      cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These
      results suggest that RSEP4 may play some roles in the CNS.

PMID- 15248026
TI  - The theaflavin monomers inhibit the cancer cells growth in vitro.
AB  - The inhibition effects of tea theaflavins complex (TFs), theaflavin-3-3'
      digallate (TFDG), theaflavin-3'-gallate (TF2B), and an unidentified compound (UC)
      on the growth of human liver cancer BEL-7402 cells, gastric cancer MKN-28 cells
      and acute promyelocytic leukemia LH-60 cells were investigated. TFs was obtained
      through the catalysis of catechins with immobilized polyphenols oxidase. TFDG,
      TF2B and UC were isolated from TFs with high speed countercurrent chromatography
      (HSCCC). The results showed that TF2B significantly inhibited the growth of all
      three kinds of cancer cells, TFs, TFDG and UC had some effect on BEL-7402 and MKN
      28, but little activity on LH-60. The inhibition effects of TF2B, TFDG, and UC on
      BEL-7402 and MKN-28 were stronger than TFs. The relationship coefficients between
      monomer concentration and its inhibition rate against MKN-28 and BEL-7402 were
      0.87 and 0.98 for TF2B, 0.96 and 0.98 for UC, respectively. The IC50 values of
      TFs, TF2B, and TFDG were 0.18, 0.11, and 0.16 mM on BEL-7402 cells, and 1.11,
      0.22, and 0.25 mM on MKN-28 cells respectively.

PMID- 15248027
TI  - Expression of recombinant chinese bovine enterokinase catalytic subunit in P.
      pastoris and its purification and characterization.
AB  - Enterokinase is a tool protease widely utilized in the cleavage of recombinant
      fusion proteins. cDNA encoding the catalytic subunit of Chinese bovine
      enterokinase (EKL) was amplified by PCR and then fused to the 3' end of prepro
      secretion signal peptide gene of alpha-mating factor from Saccharomyces
      cerevisiae to get the alpha-MF signal-EKL-His6 encoding gene by PCR. Then the
      whole coding sequence was cloned into the integrative plasmid pAO815 under the
      control of a methanol-inducible promoter and transformed GS115 methylotrophic
      strain of Pichia pastoris. Secreted expression of recombinant EKL-His6 was
      attained by methanol induction and its molecular weight is 43 kD. Because of the
      existence of His6-tag, EKL-His6 was easily purified from P. pastoris fermentation
      supernatant by using Ni2+ affinity chromatography and the yield is 5.4 mg per
      liter of fermentation culture. This purified EKL-His6 demonstrates excellent
      cleavage activity towards fusion protein containing EK cleavage site.

PMID- 15248028
TI  - Phase II study of doxorubicin and cisplatin in patients with metastatic
      hepatocellular carcinoma.
AB  - OBJECTIVE: The outcome of systemic chemotherapy in metastatic hepatocellular
      carcinoma (HCC) patients had been disappointing. Based on the demonstrated
      antitumor activities and different mechanisms of action and toxicity profiles, we
      designed a phase II trial of combination therapy with doxorubicin and cisplatin
      in metastatic HCC patients anticipating a synergistic interaction of the
      combination. METHODS: From January 1998 to January 2003, 42 consecutive patients
      with metastatic HCC were accrued. The regimen consisted of doxorubicin 60 mg/m2
      delivered as an intravenous infusion over 30 min on day 1, followed by cisplatin
      60 mg/m2 infused over 1 h on day 1. The cycle was repeated every 28 days. The
      objective tumor response was evaluated after two or three courses of
      chemotherapy. The serum alpha-fetoprotein level was measured at the start of
      every cycle. RESULTS: In total, 122 cycles of the regimen were administered, with
      a median of three cycles per patient (range one to eight cycles). The median age
      of the patients was 45 years (range 19-61 years), and 37 were evaluable for
      treatment response. The objective response rate was 18.9% (95% CI 8.0-35%) with
      one complete response and six partial responses. Six patients (16.2%) had stable
      disease and 24 patients (64.9%) had progression. Median overall survival of 37
      patients was 7.3 months (95% CI 5.9-8.6 months). The median time to progression
      of all evaluable patients was 6.6 months (95% CI 5.4-7.8 months). Of 37 evaluable
      patients, 12 32.4%, 95% CI 18.0-49.8%) showed more than 50% decrease in AFP level
      from their baseline AFP and the median time to decrease in AFP by more than 50%
      was 1.8 months with a range of 0.7-4.7 months. The chemotherapy was well
      tolerated and the most common grade 3/4 side effects were neutropenia (14.3%),
      thrombocytopenia (11.9%), and diarrhea (9.5%). CONCLUSION: Combination
      chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed
      modest antitumor activity with relatively tolerable adverse effects. The
      objective response rate of the regimen was comparable to those found in other
      phase II trials, but the search for the optimal chemotherapy should be continued.

PMID- 15248029
TI  - Synergistic killing of human leukemia cells by antioxidants and trichostatin A.
AB  - PURPOSE: Antioxidants and trichostatin A (TSA) are promising anticancer drugs,
      and are capable of enhancing the neoplastic toxicity of other chemicals that
      exert anticancer activity via different mechanisms. Since antioxidants and TSA
      (the specific inhibitor of histone deacetylase) are believed to combat cancer via
      different mechanisms, we sought to determine whether combining them would improve
      their anticancer activity in human leukemia cells (HL-60). MATERIALS AND METHODS:
      HL-60 cells were treated with antioxidants (ascorbic acid, AA and N-acetyl
      cysteine, NAC), TSA or their combination, and cell proliferation arrest, lactate
      dehydrogenase (LDH) release and cell viability were measured as indicators of
      cell damage. Accumulation of reactive oxygen species (ROS) and the acetylation of
      histones were also measured. RESULTS: The cytotoxicity of AA, NAC and TSA
      increased in a time- and dose-dependent manner. AA (1, 2 and 4 mM) and NAC (0.2,
      0.5 and 1 mM) were able to diminish ROS generation but showed no influence on
      histone acetylation in HL-60 cells. In contrast, TSA (20, 50, 100 and 200 nM) did
      not inhibit ROS generation but significantly increased histone acetylation,
      indicating a possible role for both scavenging ROS and increasing histone
      acetylation in the induction of cell death in HL-60 cells. This conclusion was
      further confirmed by the finding that the combination of antioxidant and TSA not
      only diminished ROS generation, but also increased histone acetylation, and hence
      showed greater cytotoxicity in HL-60 cells than either component alone.
      CONCLUSIONS: Our findings show that combining antioxidants and TSA can enhance
      their neoplastic toxicity at least in human leukemia HL-60 cells, providing a new
      approach to the design of chemotherapy strategies and the development of
      anticancer drugs.

PMID- 15248030
TI  - Inhibition of P-glycoprotein activity and reversal of cancer multidrug resistance
      by Momordica charantia extract.
AB  - PURPOSE: Multidrug resistance (MDR) is known as a problem limiting the success of
      therapy in patients treated long term with chemotherapeutic drugs. The drug
      resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein
      (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this
      study, novel chemical modulator(s) from bitter melon (Momordica charantia L.)
      extracts obtained from leaves, fruits and tendrils were tested for their
      abilities to modulate the function of Pgp and the MDR phenotype in the multidrug
      resistant human cervical carcinoma KB-V1 cells (high Pgp expression) in
      comparison with wildtype drug-sensitive KB-3-1 cells (lacking Pgp). METHODS: The
      KB-V1 and KB-3-1 cells were exposed to bitter melon extracts in the presence of
      various concentrations of vinblastine, and cytotoxicity was assessed by means of
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      colorimetric assay. Relative resistance was calculated as the ratio of the IC50
      value of the KB-V1 cells to the IC50 value of the KB-3-1 cells. Accumulation and
      efflux of vinblastine in KB-V1 and KB-3-1 cells were measured using a [3H]
      vinblastine incorporation assay. RESULTS: The leaf extracts increased the
      intracellular accumulation of [3H]-vinblastine in KB-V1 cells in a dose-dependent
      manner, but extracts from the fruits and tendrils had no effect. By modulating
      Pgp-mediated vinblastine efflux, the leaf extracts decreased the [3H]-vinblastine
      efflux in KB-V1 cells in a dose-dependent manner, but not in KB-3-1 cells.
      Treatment of drug-resistant KB-V1 cells with bitter melon leaf extracts increased
      their sensitivity to vinblastine, but similar treatment of KB-3-1 cells showed no
      modulating effect. The fruit and tendril extracts did not affect the MDR
      phenotype in either cell line. CONCLUSION: The leaf extracts from bitter melon
      were able to reverse the MDR phenotype, which is consistent with an increase in
      intracellular accumulation of the drug. The exact nature of the active components
      of bitter melon leaf extracts remains to be identified.

PMID- 15248031
TI  - Genetic polymorphism of NK receptors and their ligands in melanoma patients:
      prevalence of inhibitory over activating signals.
AB  - Antitumor cytotoxicity of NK cells and T cells expressing NK-associated receptors
      is regulated by interaction between their cell surface killer immunoglobulin-like
      receptors (KIRs) and CD94/NKG2 heterodimers with MHC class I ligands on target
      cells. To test the hypothesis that KIR and/or HLA polymorphisms, and KIR/HLA
      combinations could contribute to the tumorigenesis, association studies were
      performed in 50 patients with malignant melanoma (MM) in different stages of
      disease and 54 controls. Our data showed that the frequency of inhibitory and
      activating KIR genes and KIR genotypes did not differ significantly between
      healthy individuals and melanoma patients. HLA haplotype distribution showed
      statistically significant increased frequencies of A*01-B*35-Cw*04 (0.069 vs
      0.000; pc < 0.05; OR = 19.9), A*01-B*08-DRB1*03 (0.079 vs 0.019; pc < 0.05; OR =
      4.5), and A*24-B*40-DRB1*11 (0.026 vs 0.000; pc < 0.05; OR = 7.1) in melanoma
      patients compared with healthy controls. Individuals homozygous for group 2 HLA-C
      ligands were less frequent in the patient group compared with the control cohort
      (12% vs 31.5%; p < 0.017). In addition, we observed an increased frequency (88.0%
      vs 68.5%; p = 0.017; OR = 2.80) of KIR2DL2/2DL3 in combination with their group 1
      HLA-C ligands, while the presence of these KIRs in the absence of the putative
      ligands was decreased (12.0% vs 31.5%; p = 0.017) in the patient group.
      Furthermore, an increased frequency of activating KIR2DS1 in the absence of the
      putative HLA-C(Lys80) ligands was found in melanoma patients (16.0% vs 9.2%). In
      contrast, KIR2DS2 was absent in patients more often (38.0% vs 25.9%) when the
      presumptive HLA-C(Asn80) ligands were present. A slightly higher incidence of
      KIR3DL1 in combination with the less effective Bw4(Thr80) ligands was seen in
      patients with primary (20.8%) compared with metastatic (4.2%) disease. The data
      obtained in this study imply that there may not be a direct association between
      KIR gene content in the genome and the presence of malignant melanoma, or
      melanoma progression. However, some HLA haplotypes could be predisposing to MM in
      the Bulgarian population. Furthermore, distinct KIR/HLA ligand combinations may
      be relevant to the development of malignancy whereby inhibition overrides
      activation of NK cells and T cells expressing NK-associated receptors, which in
      turn might facilitate tumor escape and progression.

PMID- 15248032
TI  - Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent
      glioma.
AB  - PURPOSE: The prognosis of patients with recurrent gliomas depends on reliable and
      early diagnosis of tumour recurrence after initial therapy. In this context,
      magnetic resonance imaging (MRI) and computed tomography (CT) often fail to
      differentiate between radiation- and tumour-induced contrast enhancement.
      Furthermore, absence of contrast enhancement, or even of 18F-fluorodeoxyglucose
      uptake in PET, does not exclude recurrence. The aim of this study was to
      establish the diagnostic value of O-(2-[18F]fluoroethyl)- L-tyrosine (FET) PET in
      recurrent gliomas. METHODS: Fifty-three patients with glioma (primary grading:
      27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected
      recurrence underwent FET PET scans 4-180 months after different treatment
      modalities. For semiquantitative evaluation, maximal SUV (SUVmax) and mean SUV
      within 80% and 70% isocontour thresholds (SUV80/SUV70) were evaluated and the
      respective ratios to the background (BG) were calculated. PET results were
      correlated with MRI/CT, clinical follow-up or biopsy findings. RESULTS: All
      patients presented with FET uptake, of varying intensity, in the area of the
      primary tumour after initial therapy. In the 42 patients with confirmed
      recurrence, there was additional distinct focal FET uptake with significantly
      higher values compared with those in the 11 patients without clinical signs of
      recurrence and showing only low and homogeneous FET uptake at the margins of the
      resection cavity. With respect to tumour grading, there was a slight but non
      significant increase from WHO II (SUVmax/BG: 2.53+/-0.28) to WHO III (SUVmax/BG:
      2.84+/-0.49) and WHO IV (SUVmax/BG: 3.55+/-1.07) recurrence. CONCLUSION: FET PET
      reliably distinguishes between post-therapeutic benign lesions and tumour
      recurrence after initial treatment of low- and high-grade gliomas.

PMID- 15248033
TI  - Side-by-side reading of PET and CT scans in oncology: which patients might profit
      from integrated PET/CT?
AB  - PURPOSE: Most early publications on integrated positron emission
      tomography/computed tomography (PET/CT) devices have reported the new scanner
      generation to be superior to conventional PET. However, few of these studies have
      analysed the situation where, in addition to PET, a current CT scan is available
      for side-by-side viewing. This fact is important, because combined PET/CT or a
      software-based fusion of the two modalities may improve diagnosis only in cases
      where side-by-side reading of PET and CT data does not lead to a definitive
      diagnosis. The aim of this study was to analyse which patients will profit from
      integrated PET/CT in terms of lesion characterization. METHODS: A total of 328
      consecutively admitted patients referred for PET in whom a current CT scan was
      available were included in the study. The localization of all pathological PET
      lesions, as well as possible infiltration of adjacent anatomical structures, was
      assessed. RESULTS: Of 467 pathological lesions, 94.0% were correctly assessed
      with respect to localization and infiltration by either conventional PET alone
      (51.6%) or combined reading of PET and the already existing CT scans (42.4%).
      Hence, in only 6.0% of all lesions, affecting 6.7% of all patients, could
      evaluation have profited from integrated PET/CT. CONCLUSION: We conclude that
      side-by-side viewing of PET and CT scans is essential, as in 42.4% of all cases,
      combined viewing was important for a correct diagnosis in our series. In up to
      6.7% of patients, integrated PET/CT might have given additional information, so
      that in nearly 50% of patients some form of combined viewing of PET and CT data
      is needed for accurate lesion characterization.

PMID- 15248034
TI  - Florid reactive periostitis of the hands.
AB  - Reactive periostitis of the hand can be a confounding lesion on both radiological
      and histological grounds. An erroneous diagnosis of a malignant tumor,
      particularly an osteosarcoma, is a possibility. Two cases of florid reactive
      periostitis of the hand mistaken for osteosarcoma are reported here to illustrate
      this entity and caution against a diagnostic pitfall.

PMID- 15248035
TI  - Nodular fasciitis of the finger.
AB  - Nodular fasciitis is a benign reactive lesion, often mistaken for a soft tissue
      sarcoma in clinical practice. Involvement of the finger is very rare and, as a
      result, in this location the lesion has sometimes been treated by ray amputation
      because of misdiagnosis. We report on the clinical and histological features of
      nodular fasciitis in a 30-year-old man who was treated by excisional biopsy.
      There has been no evidence of local recurrence at the recent follow-up 8 years
      after surgery. The importance of careful histological examination to avoid
      radical surgery should be emphasized because marginal excision can provide good
      results in the treatment of nodular fasciitis.

PMID- 15248036
TI  - Synthesis of flavor and fragrance esters using Candida antarctica lipase.
AB  - Candida antarctica lipase fraction B (CAL-B) showed substrate specificity in the
      synthesis of esters in hexane involving reactions of short-chain acids having
      linear (acetic and butyric acids) and branched chain (isovaleric acid)
      structures, an unsaturated (tiglic acid) fatty acid, and phenylacetic acid with n
      butanol and geraniol. The variation in the conversion to the esters was ca. 10%.
      Similar results were observed in a study of the alcohol specificity of the enzyme
      for esterification of acetic and butyric acids with four alcohols: n-butyl,
      isopentyl, 2-phenylethyl, and geraniol. Enantioselectivity of CAL-B in hexane
      with a range of chiral alpha-substituted or beta-substituted carboxylic acids and
      n-butyl alcohol was analyzed. The results show that CAL-B can be employed as a
      robust biocatalyst in esterification reactions due to the high conversions
      obtained in the synthesis of short-chain flavor esters in an organic solvent,
      although this enzyme exhibited modest enantioselectivity with chiral short-chain
      carboxylic acids.

PMID- 15248037
TI  - Chestnut bur-shaped aggregates of chrysotile particles enable inoculation of
      Escherichia coli cells with plasmid DNA.
AB  - In the present study, Escherichia coli cells exhibited antibiotic resistance
      after transformation with exogenous plasmid DNA adsorbed onto chrysotile
      particles during agar-exposure. We previously demonstrated penetration of E. coli
      by chrysotile particles during agar-exposure. To further investigate the
      mechanism by which transformation of E. coli is achieved through the use of
      chrysotile fibers, the interaction between E. coli cells and chrysotile was
      examined during agar-exposure. Dispersion of chrysotile particles within the
      chrysotile solution was analyzed by flow cytometry. A suspension containing E.
      coli cells expressing blue fluorescence protein and chrysotile particles was
      exposed to agar using stirring apparatus, which allowed a constant vertical
      reaction force to be applied to the surface of the gel. Fluorescence microscopy
      was then used to illustrate the adsorption of fluorescein isothiocyanate
      conjugated DNA oligomers to chrysotile. Larger aggregates were observed when
      increasing concentrations of chrysotile were added to the solution. With
      prolonged exposure, during which surface moisture diffused into the agar gel,
      greater concentrations of chrysotile were observed on the agar surface. In
      addition, chrysotile aggregates exceeding 50 microm developed on the agar
      surface. They were shaped like a chestnut bur. The chrysotile aggregates
      penetrated the cell membranes of adherent E. coli cells during agar-exposure due
      to sliding friction forces generated at the interface of the agar and the
      stirring stick. E. coli cells thus acquired plasmid DNA and antibiotic
      resistance, since the plasmid DNA had been adsorbed onto the chrysotile
      particles. The inoculation of plasmid DNA into E. coli cells demonstrates the
      usefulness of chrysotile for E. coli transformation.

PMID- 15248038
TI  - Hyper-production of an isomalto-dextranase of an Arthrobacter sp. by a proteases
      deficient Bacillus subtilis: sequencing, properties, and crystallization of the
      recombinant enzyme.
AB  - Arthrobacter globiformis T6 is unique in that it produces an enzyme yielding only
      isomaltose from dextran. In the present study, the organism was re-identified and
      its classification as a new species of the genus Arthrobacter, A. dextranlyticum,
      was proposed. The high G+C gene (66.8 mol%) for the isomalto-dextranase was
      sequenced. The deduced amino acid sequence, with a calculated molecular mass of
      65,993 Da (603 amino acids), was confirmed by nanoscale capillary liquid
      chromatography coupled to tandem mass spectrometry, which covered 71.1% of the
      amino acid residues of the entire sequence. The enzyme was grouped into glycoside
      hydrolase family 27, and the C-terminal domain has homology to carbohydrate
      binding module family 6. Hyper-exoproduction of the recombinant enzyme was
      achieved at a level corresponding to approximately 4.6 g l(-1) of culture broth
      when proteases-deficient Bacillus subtilis cells were used as the host. The
      purified enzyme (65.5 kDa) had an optimal pH and temperature for activity of 3.5
      and 60 degrees C, respectively. It was crystallized using the sitting-drop vapor
      diffusion method at 293 K.

PMID- 15248039
TI  - Strategies for bioremediation of polychlorinated biphenyls.
AB  - Polychlorinated biphenyls (PCBs) are serious environmental pollutants that
      threaten both the natural ecosystem and human health. For remediation of
      environments contaminated with PCBs, several approaches that exploit the
      potential of microbes to degrade PCBs have been developed. These approaches
      include improvement of PCB solubilization and entry into the cell, pathway and
      enzyme engineering, and control of enzyme expression. In this mini-review, we
      briefly summarize these strategies and provide potentially useful knowledge for
      the further improvement of the bacterial breakdown of PCBs.

PMID- 15248040
TI  - Current studies on biological tagatose production using L-arabinose isomerase: a
      review and future perspective.
AB  - D-Tagatose is a hexoketose monosaccharide sweetener, which is an isomer of D
      galactose and is rarely found in nature. Recently, there has been industrial
      interest in D-tagatose as a low-calorie sugar-substituting sweetener. This
      article describes the properties and metabolism of tagatose as well as its
      commercial importance. The comparison between the biological tagatose production
      and the chemical production was reviewed based on the example of the glucose
      isomerization into fructose. The industrial problems facing its commercial
      application is described and evolving potential solutions are suggested.

PMID- 15248041
TI  - Biotechnological lycopene production by mated fermentation of Blakeslea trispora.
AB  - A semi-industrial process (800-l fermentor) for lycopene production by mated
      fermentation of Blakeslea trispora plus (+) and minus (-) strains has been
      developed. The culture medium was designed at the flask scale, using a program
      based on a genetic algorithm; and a fermentation process by means of this medium
      was developed. Fermentation involves separate vegetative phases for (+) and (-)
      strains and inoculation of the production medium with a mix of both together.
      Feeding with imidazole or pyridine, molecules known to inhibit lycopene cyclase
      enzymatic activity, enhanced lycopene accumulation. Different raw materials and
      physical parameters, including dissolved oxygen, stirring speed, air flow rate,
      temperature, and pH, were checked in the fermentor to get maximum lycopene
      production. Typical data for the fermentation process are presented and
      discussed. This technology can be easily scaled-up to an industrial application
      for the production of this carotenoid nowadays widely in demand.

PMID- 15248042
TI  - Formation and analysis of mannosylerythritol lipids secreted by Pseudozyma
      aphidis.
AB  - Pseudozyma aphidis DSM 70725 was found to be a novel producer of
      mannosylerythritol lipids (MELs). The MELs were quantified by HPLC. Glucose as
      carbon source for precultivation supported growth well. By contrast, at
      concentrations >30 g l(-1) in preculture, subsequent MEL formation in the main
      culture with soybean oil as sole carbon source was reduced. The type of substrate
      supply considerably influenced MEL formation. High concentrations of soybean oil
      (80 ml l(-1)) at init favored the production process when compared to a stepwise
      (20 ml l(-1)) addition. Mannose or erythritol were suitable second carbon sources
      that enhanced the MEL yield with soybean oil as preferred primary substrate.
      After 10 days, a maximum yield of 75 g l(-1) was attained during shake-flask
      cultivation. Biofuel (rapeseed oil methyl ester) also resulted in high yields of
      MEL, but glucose reduced the MEL yield. Analysis by GC-MS showed that all fatty
      acids contained in MEL and derived from soybean oil or related methyl ester were
      degraded by C2-units to differing extents. The surface (water/air) and
      interfacial (water/hexadecane) tension of the MELs produced from different carbon
      sources were reduced to a minimum of 26.2 mN m(-1) and 1 mN m(-1), respectively.

PMID- 15248043
TI  - Correlation of orofacial speeds with voice acoustic measures in the fluent speech
      of persons who stutter.
AB  - Stuttering is often viewed as a problem in coordinating the movements of
      different muscle systems involved in speech production. From this perspective, it
      is logical that efforts be made to quantify and compare the strength of neural
      coupling between muscle systems in persons who stutter (PS) and those who do not
      stutter (NS). This problem was addressed by correlating the speeds of different
      orofacial structures with vowel fundamental frequency (F0) and intensity as
      subjects produced fluent repetitions of a simple nonsense phrase at habitual,
      high, and low intensity levels. It is assumed that resulting correlations
      indirectly reflect the strength of neural coupling between particular orofacial
      structures and the respiratory-laryngeal system. An electromagnetic system was
      employed to record movements of the upper lip, lower lip, tongue, and jaw in 43
      NS and 39 PS. The acoustic speech signal was recorded and used to obtain measures
      of vowel F0 and intensity. For each subject, correlation measures were obtained
      relating peak orofacial speeds to F0 and intensity. Correlations were
      significantly reduced in PS compared to NS for the lower lip and tongue, although
      the magnitude of these group differences covaried with the correlation levels
      relating F0 and intensity. It is suggested that the group difference in
      correlation pattern reflects a reduced strength of neural coupling of the lower
      lip and tongue systems to the respiratory-laryngeal system in PS. Consideration
      is given to how this may contribute to temporal discoordination and stuttering.

PMID- 15248045
TI  - Relative antioxidant capacities of propofol and its main metabolites.
AB  - The antioxidant activity of propofol, a widely used anesthetic, has previously
      been demonstrated, but no study has focused on propofol metabolites although
      propofol undergoes extensive metabolism. In the present study, the antioxidant
      properties of propofol and its metabolites were studied by measuring
      malondialdehyde (MDA) produced from lipid peroxidation by microsomes triggered
      with several free radical generating systems. True MDA determination was
      performed using a specific high performance liquid chromatography technique. Gas
      chromatography-isotope ratio mass spectrometry methodology was also used to
      assess the antioxidant action in a homogeneous aqueous environment. Propofol, 2,6
      di-isopropyl-1,4-quinol (1,4-quinol) metabolite and 3,5-di- tert-butyl-4
      hydroxytoluene markedly inhibit lipid peroxidation at concentrations lower than 5
      microM. The binding of the glucuroconjugated moiety to either one of two hydroxyl
      groups of 1,4-quinol lowers the radical scavenging activity. Propofol glucuronide
      did not exert any radical scavenging activity except when peroxidation was
      induced with tert-butylhydroperoxide. Our data demonstrate that propofol and its
      metabolites inhibit lipid peroxidation at concentrations similar to those
      measured in human plasma during anesthesia. Their antioxidant efficiency is
      influenced by several factors, including the type of radical initiator involved
      and the site of radical production.

PMID- 15248044
TI  - Genetic features of antidepressant induced mania and hypo-mania in bipolar
      disorder.
AB  - RATIONALE AND OBJECTIVES: The present study investigated possible genetic
      association between some polymorphisms possibly involved in antidepressant
      response and the occurrence of manic or hypo-manic switches during antidepressant
      treatment. METHODS: We retrospectively examined 169 individuals with a diagnosis
      of bipolar disorder (BP) type I ( n=103) and II ( n=66), who presented at least
      one sudden manic or hypo-manic episode (according to DSM IV criteria) during
      antidepressant therapy, that occurred within a period of 3 weeks from the
      beginning of the treatment and without any interposed period of well being
      ("manic switch"). They were compared with a sex, age, and ethnicity-matched group
      of 247 subjects, randomly selected from our pool of bipolar subjects, who never
      showed switches. We then randomly selected from the whole sample ("switched" and
      "not switched") a sub-sample of patients not under mood stabiliser treatment at
      the time of the index episode (65 "switched" and 117 "not switched") and compared
      them with a sex, age and ethnicity matched group of 133 subjects, randomly
      selected from our pool of major depressed patients, who did not present manic
      switches. The functional polymorphism in the upstream regulatory region of the
      serotonin transporter (SERTPR), tryptophan hydroxylase (TPH), G-protein beta 3
      subunit (Gbeta3), monoamine oxidase A (MAO-A), catechol- O-methyltransferase
      (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2) and dopamine
      receptor D4 (DRD4) gene variants were analysed using PCR-based techniques.
      RESULTS AND CONCLUSIONS: The distribution of the genetic polymorphisms was not
      significantly different between switched and not-switched patients ( P>0.006
      Bonferroni corrected). Moreover, no significant difference was found between
      switched and not switched sub-samples and the sample of major depressed subjects.
      Further studies are required to investigate other possible related genetic
      variants influencing the timing of manic-depressive cycle.

PMID- 15248046
TI  - Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F
      cells.
AB  - AIMS/HYPOTHESIS: Cytokines are important humoral mediators of beta cell
      destruction in autoimmune diabetes. The aim of this study was to identify novel
      cytokine-induced genes in insulin-producing RINm5F cells, which may contribute to
      beta cell death or survival. METHODS: A global gene expression profile in
      cytokine-exposed insulin-producing RINm5F cells was achieved by automated
      restriction fragment differential display PCR. The expression of selected
      candidate genes was confirmed by real-time RT-PCR analysis. RESULTS: Exposure of
      RINm5F cells to IL-1beta or to a cytokine mixture (IL-1beta, TNF-alpha, IFN
      gamma) for 6 h resulted in the differential expression of a functional gene
      cluster. Apart from the well-known up-regulation of the cytokine-responsive genes
      iNOS, NF-kappaB, MnSOD and Hsp70, several genes that belong to the functional
      cluster of the endocytotic pathway were identified. These endocytotic genes
      comprised: clathrin, megalin, synaptotagmin and calcineurin, which were up
      regulated by IL-1beta or the cytokine mixture. In contrast, the expression of the
      calcineurin inhibitor CAIN and of the GDP/GTP exchange protein Rab3 was down
      regulated by cytokines. Other up-regulated cytokine-responsive genes were: agrin,
      murine adherent macrophage protein mRNA ( MAMA) and transport-associated protein
      ( TAP1/MTP), whereas the plasma membrane calcium ATPase ( PMCA) 2 and PMCA 3
      genes were down-regulated by cytokines. CONCLUSIONS/INTERPRETATION: Our results
      indicate that genes of the endocytotic pathway are regulated by pro-inflammatory
      cytokines. This might affect the density of cytokine receptors at the beta cell
      surface and concomitantly the sensitivity of the cells to cytokine toxicity. A
      better understanding of the functional cross-talk between endocytotic and
      cytokine signalling pathways could further the development of novel strategies to
      protect pancreatic beta cells against toxic effects of pro-inflammatory
      cytokines.

PMID- 15248047
TI  - Neonatal oral administration of DiaPep277, combined with hydrolysed casein diet,
      protects against Type 1 diabetes in BB-DP rats. An experimental study.
AB  - AIMS/HYPOTHESIS: Environmental factors such as diet and bacterial antigens play
      an important role in the onset of Type 1 diabetes. Different self-antigens are
      suggested to play a role in the development of diabetes. Antibodies against the
      60-kDa heat shock protein 60, which have a high homology to bacterial heat shock
      protein 65, have been found in the circulation at the onset of diabetes in humans
      and in pre-diabetic NOD-mice. One of the immunodominant epitopes in autoimmune
      diabetes is p277, a specific peptide of human heat shock protein 60 corresponding
      to positions 437-460. In this study we investigated whether neonatal oral
      administration of DiaPep277 (a synthetic peptide analogue of p277) affected the
      development of diabetes in the BioBreeding-Diabetes Prone (BB-DP) rat, and
      whether this could potentiate the effect of a protective hydrolysed casein-diet.
      METHODS: BB-DP rats were orally inoculated once per day with placebo or DiaPep277
      at days 4, 5, 6 and 7 of life. At the age of 21 days rats were weaned on to a
      conventional, cereal-based diet or on to the hydrolysed casein-diet. RESULTS: The
      development of diabetes in animals receiving DiaPep277 in combination with the
      hydrolysed casein-diet was delayed by 17 days, and a relative reduction of the
      incidence by 64% was seen. Non-diabetic animals did not show any sign of
      insulitis. CONCLUSIONS/INTERPRETATION: Short-term neonatal feeding with p277 in
      early life, combined with diet adaptation, appears to provide a procedure to
      significantly reduce the development of Type 1 diabetes in later life.

PMID- 15248049
TI  - [Speech perception. The basis for speech audiometry examinations].
AB  - Speech recognition measurements are widely used in clinical applications.
      Usually, either a speech recognition threshold is determined, being defined as
      the speech level or signal-to-noise ratio that enables the patient to understand
      50% of the target words or target sentences. In other cases, a discrimination
      curve, describing speech recognition as function of the presentation level, is
      recorded. For the interpretation of these findings, it is important to keep in
      mind that speech perception is affected by many interacting sensory, perceptual
      and cognitive processes.Here, our current knowledge of these processes is
      outlined and theories that model speech perception in general are briefly
      reviewed.

PMID- 15248048
TI  - [Surgical correction of the upper and lower arm of children].
AB  - The causes of post-traumatic deformities of the upper and lower arm shafts as
      well as the complete elbow are 90% iatrogenic, in the area of the proximal
      humerus and the distal lower arm they are about 90% the result of chance
      (premature closure of the growth plate). In general, corrections of deformities
      are possible at any age, dependent on the patient's symptoms, the expected
      development, the location of the deformity and its changes during development.
      The correction technique should allow for the removal of all of the components of
      the deformity, and to retain the results until healing is complete and the
      patient's motor stability is ensured. Due to the high percentage of iatrogenic
      deformities, the optimisation of the primary therapy should receive particular
      attention rather than increasing the indications for a correction.

PMID- 15248050
TI  - [Reconstruction of visceral arteries with homografts in excision of the
      pancreas].
AB  - BACKGROUND: At present, surgical treatment with R(0) resection offers the only
      chance of cure for patients suffering from pancreatic cancer. Carcinomas of the
      pancreas are frequently diagnosed at an inoperable stage because of local tumor
      progression by vessel wall infiltration. In a small series of patients, efforts
      have been made to increase curative resection rates for advanced pancreatic
      cancer by excision and reconstruction of the involved visceral arteries. Whether
      this provides clinical benefit remains uncertain. METHODS: Since 2001 we have
      been employing "en bloc" tumor resection for advanced pancreatic carcinomas with
      extended infiltration of visceral vessels. Technical experience was gained
      previously by performing portal vein resection as well as arterial excision and
      reconstruction by direct anastomosis in the presence of malignant wall
      infiltration. A total of ten patients underwent vascular reconstruction by
      arterial homograft interposition. In six of ten cases, combined extended
      reconstructions of the hepatic and superior mesenteric arteries were performed.
      One patient died during the perioperative course due to fulminant bleeding. One
      patient developed severe diarrhea. During a 3- to 18-month follow-up, one case of
      liver metastasis and one case of local tumor recurrence were documented.
      CONCLUSIONS: In selective cases, operability and R(0) resection can be achieved
      in advanced pancreatic cancer by performing extended resection procedures with
      vascular reconstruction using arterial homografts. Vascular substitution of
      visceral arteries can be conducted without ischemic disturbances of the small
      bowel and liver. Only a few perioperative complications were observed.

PMID- 15248051
TI  - [liposarcoma. Aspects of pathomorphology--an analysis of 209 tumos].
AB  - BACKGROUND: Among the heterogeneous group of adult soft tissue sarcomas,
      liposarcomas represent the largest entity along with malignant fibrous
      histiocytomas (MFH). PATIENTS AND METHODS: This article summarizes the results of
      pathomorphological data on 209 liposarcomas resected over a 10-year period.
      RESULTS: The most common tumor site was the thigh, and the peak age incidence was
      in the 5th and 6th decades. In general, three major subtypes of liposarcoma can
      be distinguished in terms of pathomorphology: well
      differentiated/dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and
      pleomorphic liposarcoma. Well-differentiated liposarcomas represent malignancy
      grade 1 tumors without biological potential to metastasize, but which are able to
      relapse locally in cases of incomplete resection. When a local relapse has
      occurred, the liposarcoma may show dedifferentiation and may metastasize.
      CONCLUSIONS: In the pathologic-anatomical diagnosis of liposarcomas, conventional
      light-microscopic findings are decisive. Additional methods of molecular
      pathology may help in single cases to gain further insights.

PMID- 15248052
TI  - Evaluation of the chemomechanical removal of dentine caries in vivo with a new
      modified Carisolv gel.
AB  - Carisolv is a minimally invasive method for softening and removing dentine
      caries. A new, modified Carisolv gel has been developed in order to optimise the
      efficiency if its chemical caries dissolution. The aim of the present study was
      to compare the caries removal efficiency of the original gel with that of the new
      gel, which contains almost double the concentration of sodium hypochlorite. Ten
      dentists treated 202 cavities in 170 patients; 104 cavities were randomised to
      the new gel and 98 to the original gel. Their mean treatment times for caries
      removal were 6.7+/-4.1 min and 7.6+/-4.2 min, respectively ( P>0.05). In close-to
      pulp lesions, constituting 32% of the cavities, the mean times for caries removal
      were 9.0+/-7.0 min and 11.6+/-4.4 min for the new and original gels, respectively
      ( P<0.01). Questionnaires revealed that 81% of the patients preferred
      chemomechanical treatment to drilling. In conclusion, the improved efficiency of
      the modified Carisolv gel did reduce the time for caries removal in deep lesions.
      However, it still needs more time than conventional drilling.

PMID- 15248053
TI  - Marginal and internal adaptation of Class II ormocer and hybrid resin composite
      restorations before and after load cycling.
AB  - To overcome the shortcomings of the conventional composite restorative materials,
      ormocer materials have been introduced over the past few years. The purpose of
      this study was to evaluate the marginal and internal adaptation of two ormocer
      restorative systems (Admira, Voco and Definite, Degussa) compared to a hybrid
      composite one (TPH Spectrum, Dentsply/ DeTrey), before and after load cycling in
      Class II restorations. Standardized Class II restorations with cervical margins
      on enamel were divided into three groups ( n=16). Teeth of each group were filled
      with one of the restoratives tested and its respective bonding agent. Each group
      was divided into two equal subgroups. The marginal and internal adaptation of the
      first subgroup was evaluated after 7-day water storage at room temperature and of
      the second after cyclic loading in a mastication simulator (1.2x10(6) cycles, 49
      N, 1.6 Hz). The occlusal and cervical marginal evaluation was conducted by
      videomicroscope and ranked as "excellent" and "not excellent". One thin section
      (150 microm), in mesial-distal direction, of each restoration, was examined under
      metallographic microscope to determine the quality of internal adaptation. The
      occlusal and cervical adaptation of both ormocer restorative systems was similar
      and clearly worse compared with the hybrid composite restorative one before as
      well as after load cycling. Concerning internal adaptation, no gap-free ormocer
      restorations were detected, whereas all Spectrum restorations presented perfect
      adaptation. The bonding agents of the ormocers formed layers with unacceptable
      features (pores, fractures) whereas that of the hybrid composite achieved perfect
      bonding layer even after loading. The rheological characteristics of the bonding
      agents of the ormocer restorative systems are proposed to be responsible for
      their inferior marginal and internal quality in Class II restorations compared
      with the hybrid composite one.

PMID- 15248055
TI  - Effect of constrained posterior screw and rod systems for primary stability:
      biomechanical in vitro comparison of various instrumentations in a single-level
      corpectomy model.
AB  - Cervical corpectomy is a frequently used technique for a wide variety of spinal
      disorders. The most commonly used approach is anterior, either with or without
      plating. The results for single-level corpectomy are better than in multilevel
      procedures. Nevertheless, hardware- or graft-related complications are observed.
      In the past, constrained implant systems were developed and showed encouraging
      stability, especially for posterior screw and rod systems in the lumbar spine. In
      the cervical spine, few reports about the primary stability of constrained
      systems exist. Therefore, in the present study we evaluated the primary stability
      of posterior screw and rod systems, constrained and non-constrained, in
      comparison with anterior plating and circumferential instrumentations in a non
      destructive set-up, by loading six human cadaver cervical spines with pure
      moments in a spine tester. Range of motion and neutral zone were measured for
      lateral bending, flexion/extension and axial rotation. The testing sequence
      consisted of: (1) stable testing; (2) testing after destabilization and cage
      insertion; (3a) additional non-constrained screw and rod system with lateral mass
      screws, (3b) with pedicle screws instead of lateral mass screws; (4a) constrained
      screw and rod system with lateral mass screws, (4b) with pedicle screws instead
      of lateral mass screws; (5) 360 degrees set-up; (6) anterior plate. The stability
      of the anterior plate was comparable to that of the non-constrained system,
      except for lateral bending. The primary stability of the non-constrained system
      could be enhanced by the use of pedicle screws, in contrast to the constrained
      system, for which a higher primary stability was still found in axial rotation
      and flexion/extension. For the constrained system, the achievable higher
      stability could obviate the need to use pedicle screws in low instabilities.
      Another benefit could be fewer hardware-related complications, higher fusion
      rate, larger range of instabilities to be treated by one implant system, less
      restrictive postoperative treatment and possibly better clinical outcome. From a
      biomechanical standpoint, in regard to primary stability the constrained systems,
      therefore, seem to be beneficial. Whether this leads to differences in clinical
      outcome has to be evaluated in clinical trials.

PMID- 15248056
TI  - Solvent-preserved, bovine cancellous bone blocks used for reconstruction of
      thoracolumbar fractures in minimally invasive spinal surgery-first clinical
      results.
AB  - We investigated the osseointegration of solvent-preserved, xenogenous cancellous
      bone blocks in the treatment of unstable fractures of the thoracolumbar junction.
      In 22 patients, the anterior repair procedure was performed by thoracoscopy or
      minimally invasive retroperitoneal surgery. Twenty-two patients had undergone
      monosegmental anterior fusion and were surveyed prospectively. Solvent-preserved,
      bovine cancellous bone blocks were used in 11 patients; iliac crest bone graft
      was used in the others. Follow-up after 12 months included CT scans, which
      revealed successful osseointegration in eight out of 11 patients who had received
      autogenous iliac crest bone grafts, while three patients showed a partial
      integration. There were no graft fragmentations. In patients who had received
      solvent-preserved, xenogenous cancellous bone blocks, complete osseointegration
      was achieved at the graft-bone interface in only two out of 11 cases, after 1
      year. Partial integration was found in three patients. In view of these results,
      autogenous iliac crest bone grafts are still the unrivalled standard for defect
      repair in spinal surgery.

PMID- 15248057
TI  - Healing properties of allograft from alendronate-treated animal in lumbar spine
      interbody cage fusion.
AB  - This study investigated the healing potential of allograft from bisphosphonate
      treated animals in anterior lumbar spine interbody fusion. Three levels of
      anterior lumbar interbody fusion with Brantigan cages were performed in two
      groups of five landrace pigs. Empty Brantigan cages or cages filled with either
      autograft or allograft were located randomly at different levels. The allograft
      materials for the treatment group were taken from the pigs that had been fed with
      alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in
      alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone
      volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS),
      respectively. No statistical difference was found between the same grafted cage
      comparing two groups. The histological fusion rate was 7/10 in all autograft cage
      levels and 5/10 in combined allograft cage levels. No fusion was found at all in
      empty cage levels. With the numbers available, no statistically significant
      difference was found in histological fusion between autograft and allograft
      applications. There was a significant difference of mean bone volume between
      autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did
      not demonstrate different healing properties of alendronate-treated and non
      treated allograft for anterior lumbar interbody fusion in pigs.

PMID- 15248058
TI  - [A chronic problem-the chronic headache patient].
AB  - Chronic daily headache is a frequent problem which affects 3-5% of the
      population. Until the 2nd edition of the IHS headache classification, the
      diagnosis of chronic headache was synonymous with the diagnosis of chronic
      tension type headache. Now one has to differentiate, not only in symptomatic
      headache, but also between other primary headache syndromes, such as chronic
      migraine, hemicrania continua and acute persisting daily headache.
      Epidemiological studies point to a particular importance of chronic migraine and
      headache due to chronic analgetica use, since both types of headache are
      responsible for more than 60% of all cases with chronic headache. Although the
      mechanisms which cause chronification of headache are not well understood, the
      new headache classification prompts some direct therapeutical consequences: 1)
      the indication for drug withdrawal and 2) the indication for a migraine
      preventive therapy. In general, as with other chronic pain syndromes, there is
      increasing evidence that a multimodal therapy, consisting of patient education,
      behavioral therapy and pharmacological therapy, is more successful than a
      singular therapy.

PMID- 15248059
TI  - Advantages of cyclosporin A using 2-h levels in pediatric kidney transplantation.
AB  - Clinical trials in adult liver and heart recipients have shown that management of
      cyclosporine (CsA) dose with 2-h levels (C2) leads to lower rejection rates and
      serum creatinine levels compared with C0 monitoring. Therefore, we investigated
      whether C2 monitoring might also improve late graft survival after kidney
      transplantation in children. To date, no results in adult renal transplantation
      and in pediatric transplantation have been published. Forty-nine stable pediatric
      kidney recipients with a minimum time of 1 year after transplantation (mean=7+/-5
      years) entered the study. None of the patients had experienced an acute rejection
      up to 6 months before entering the study. CsA dosing was based on C0 monitoring
      for the first 6 months and then based on C2 monitoring for the following 6
      months. C0 and C2 levels were measured at 4-weekly intervals. Percentage decline
      in glomerular filtration rate (GFR) and mean coefficients of variation of CsA
      levels (C(var)) were calculated and compared during the 6-months periods. At the
      beginning of the study, the mean calculated GFR was 53+/-15 ml/min per 1.73 m(2).
      During the 6 months of C0 monitoring, the mean GFR decreased to 49+/-12 m/min per
      1.73 m(2 )( P=0.001, paired t-test). Six months after switching to C2 monitoring,
      the mean GFR remained stable, at 49+/-15 ml/min per 1.73 m(2 )( P=0.3 paired t
      test). The largest increase in GFR (3.9+/-7.9%) was found in patients with a
      decrease of their CsA dose of more than 5% under C2 monitoring. C(var) was
      significantly lower under C2 than under C0 monitoring (0.24+/-0.10 vs. 0.30+/
      0.15, P=0.02, unpaired t-test). We conclude that the switch to C2 monitoring
      helped to identify patients with CsA overdosing as well as to reduce variation in
      CsA level, which resulted in a halt in GFR decline.

PMID- 15248060
TI  - A test of multiple hypotheses for the species richness gradient of South American
      owls.
AB  - Many mechanisms have been proposed to explain broad scale spatial patterns in
      species richness. In this paper, we evaluate five explanations for geographic
      gradients in species richness, using South American owls as a model. We compared
      the explanatory power of contemporary climate, landcover diversity, spatial
      climatic heterogeneity, evolutionary history, and area. An important aspect of
      our analyses is that very different hypotheses, such as history and area, can be
      quantified at the same observation scale and, consequently can be incorporated
      into a single analytical framework. Both area effects and owl phylogenetic
      history were poorly associated with richness, whereas contemporary climate,
      climatic heterogeneity at the mesoscale and landcover diversity explained ca. 53%
      of the variation in species richness. We conclude that both climate and
      environmental heterogeneity should be retained as plausible explanations for the
      diversity gradient. Turnover rates and scaling effects, on the other hand,
      although perhaps useful for detecting faunal changes and beta diversity at local
      and regional scales, are not strong explanations for the owl diversity gradient.

PMID- 15248061
TI  - Proximate basis of the covariation between a melanin-based female ornament and
      offspring quality.
AB  - In contradiction to sexual selection theory, several studies showed that although
      the expression of melanin-based ornaments is usually under strong genetic control
      and weakly sensitive to the environment and body condition, they can signal
      individual quality. Covariation between a melanin-based ornament and phenotypic
      quality may result from pleiotropic effects of genes involved in the production
      of melanin pigments. Two categories of genes responsible for variation in melanin
      production may be relevant, namely those that trigger melanin production (yes or
      no response) and those that determine the amount of pigments produced. To
      investigate which of these two hypotheses is the most likely, I reanalysed data
      collected from barn owls ( Tyto alba). The underparts of this bird vary from
      immaculate to heavily marked with black spots of varying size. Published cross
      fostering experiments have shown that the proportion of the plumage surface
      covered with black spots, a eumelanin composite trait so-called "plumage
      spottiness", in females positively covaries with offspring humoral
      immunocompetence, and negatively with offspring parasite resistance (i.show
      $132#e. the ability to reduce fecundity of ectoparasites) and fluctuating
      asymmetry of wing feathers. However, it is unclear which component of plumage
      spottiness causes these relationships, namely genes responsible for variation in
      number of spots or in spot diameter. Number of spots reflects variation in the
      expression of genes triggering the switch from no eumelanin production to
      production, whereas spot diameter reflects variation in the expression of genes
      determining the amount of eumelanin produced per spot. In the present study,
      multiple regression analyses, performed on the same data sets, showed that
      humoral immunocompetence, parasite resistance and wing fluctuating asymmetry of
      cross-fostered offspring covary with spot diameter measured in their genetic
      mother, but not with number of spots. This suggests that genes responsible for
      variation in the quantity of eumelanin produced per spot are responsible for
      covariation between a melanin ornament and individual attributes. In contrast,
      genes responsible for variation in number of black spots may not play a
      significant role. Covariation between a eumelanin female trait and offspring
      quality may therefore be due to an indirect effect of melanin production.

PMID- 15248062
TI  - Molecular characterization and expression of p63 isoforms in human keloids.
AB  - Keloids are benign skin tumors that develop following wounding. A cDNA product
      from human keloid specimens was identified using the differential display
      technique. The full-length cDNA was cloned by RT-PCR using human keloid mRNA as
      template. The predicted product of the cDNA was found to be 99% identical to the
      DeltaN-p63 gamma isotype of p63, a transcription factor that belongs to the
      family that includes the structurally related tumor suppressor p53 and p73. The
      DeltaN-p63 isotype lacks the acidic N terminal region corresponding to the
      transactivation domain of p53. Since this can potentially block p53-mediated
      target gene transactivation, it may serve as a dominant-negative isoform. Real
      Time RT-PCR analysis of RNAs from normal skin tissue and keloids showed that the
      DeltaN-p63 isotype is specifically expressed in keloids, but is virtually
      undetectable in normal skin. Immunostaining of p63 in normal skin revealed that
      only basal cells of the epithelium expressed the protein, while in keloid tissues
      the antigen was detected in the nuclei of cells scattered through all layers of
      the epithelium and in fibroblast-like cells in the dermis. These results may
      indicate that aberrant p63 expression plays a role not only in malignant tumors
      but also in benign skin diseases that show hyperproliferation of epidermal cells
      in vivo. Moreover, this isoform of p63 could serve as a specific molecular marker
      for this human disease.

PMID- 15248063
TI  - The neural crest is contiguous with the cardiac conduction system in the mouse
      embryo: a role in induction?
AB  - In this study we present data on the spatial relationship between neural crest
      derived cells (NCC) and the specialized cardiac conduction system (CCS) in the
      developing murine heart. Using Wnt1-Cre/R26R conditional reporter mice that
      express beta-galactosidase from ROSA26 upon Cre-mediated recombination, two
      populations of NCC are seen: one migrates through the arterial pole and
      contributes to the bundle branches, whereas the second population enters by way
      of the venous pole and provides cells to the sinoatrial and atrioventricular node
      areas. The CCS/ lacZ construct is found in the myocardium of the early embryonic
      heart and afterward only persists in the definitive CCS and is acknowledged as a
      reporter for the developing conduction system. The contiguous expression of both
      reporters is suggestive for a potential role of cardiac NCC in the induction of
      the final differentiation of the CCS.

PMID- 15248064
TI  - Small-cell carcinoma of the urinary bladder. A clinico-pathological study of ten
      cases.
AB  - Small-cell carcinoma (SCC) of the urinary bladder is an infrequent neoplasia
      accounting for 0.5% of all tumors located at this level. There is a predilection
      for males over females with a 4:1 proportion and a median age of 66 years. In
      most cases, the initial diagnosis is made at the metastatic or progressive stage
      of the disease. For this study, we collected ten cases of SCC of the urinary
      bladder, diagnosed over a period of 16 years, to describe the morphological and
      immunocytochemical characteristics of these infrequent neoplasia. In all cases,
      clinical data such as age at presentation, personal background, clinical
      symptoms, stage, treatment, clinical outcome and present status were available.
      Primary antibodies included chromogranin, neuron-specific enolase, synaptophysin,
      PGP 9.5, HNK-1, cytokeratin 34betaE12, cytokeratin 20, thyroid transcription
      factor-1 (TTF-1), c-erbB2 (CB-11), p53 (DO7), and Ki67 (MIB-1). In addition to
      the expression of neural/neuroendocrine markers, immunostaining for p53 and c
      erbB2 was found in 80% and 50% of cases, respectively. In this paper, we confirm
      the aggressive course of the neoplastic disease. The expression of c-erbB2 in 50%
      of cases opens up hypothetical new possibilities for the use of immunotherapy in
      such cases.

PMID- 15248065
TI  - Nuclear fusions contribute to polyploidization of the gigantic nuclei in the
      chalazal endosperm of Arabidopsis.
AB  - Somatic polyploidization is recognized as a means to increase gene expression
      levels in highly active metabolic cells. The most common mechanisms are
      endoreplication, endomitosis and cell fusion. In animals and plants the nuclei of
      multinucleate cells are usually prevented from fusing. Here, we report that the
      nuclei from the syncytial cyst of the chalazal endosperm of Arabidopsis thaliana
      (L.) Heynh. are polyploid with some intermediate ploidy levels that cannot be
      attributed to endoreplication, suggesting nuclear fusion. Analysis of isolated
      nuclei, together with fluorescent in situ hybridization (FISH), revealed that
      nuclei from the chalazal endosperm are two or three times bigger than the nuclei
      from the peripheral endosperm and have a corresponding increase in ploidy.
      Together with the consistent observation of adjoined nuclei, we propose that
      nuclear fusion contributes, at least in part, to the process of polyploidization
      in the chalazal endosperm. Confocal analysis of intact seeds further suggested
      that free nuclei from the peripheral endosperm get incorporated into the chalazal
      cyst and likely participate in nuclear fusions.

PMID- 15248066
TI  - Bronchiolar expression of aquaporin-3 (AQP3) in rat lung and its dynamics in
      pulmonary oedema.
AB  - Aquaporins (AQPs) are water channel proteins that permit osmotically driven water
      movement. To determine their dynamics in pulmonary oedema, we examined the
      expression of mRNA and protein for AQP1, AQP3, AQP4, and AQP5 in the lungs of
      normal and thiourea-treated rats. In the thiourea group, lung water content
      increased significantly (vs. controls) with the peak at around 4 h. Semi
      quantitative RT-PCR showed that AQP3 mRNA in the thiourea group rose
      significantly, peaking at around 4-8 h. The expression of AQP1, AQP4, AQP5, ENaC
      and CFTR mRNA each decreased significantly some time after the peak in lung water
      content. Immunoblot analysis showed that glycosylated AQP3 protein was increased
      4-10 h after treatment. Expression of the other AQP proteins was not
      significantly altered, except for that of AQP4. Immunohistochemical examination
      revealed that AQP1 was expressed in endothelia, AQP3 in the basal cells of the
      large airways and in cuboidal cells in the bronchioles, AQP4 in the basolateral
      membrane of airway cells and AQP5 in type-I pneumocytes. Our results suggest that
      AQP3 is expressed not only in large airways, but also in bronchioles, and is
      related to water movement in pulmonary oedema.

PMID- 15248067
TI  - Control of erythropoiesis after high altitude acclimatization.
AB  - Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a
      hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a
      3-week sojourn in the Andes. On return to sea level, increased red blood cells
      (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) ( P<0.05), and
      increased arterial partial pressure of oxygen (+8.56%), arterial oxygen
      saturation (+7.40%) and arterial oxygen blood content ( C(a)O(2)) (+12.93%) at
      the end of HH ( P<0.05) attested high altitude acclimatization. Reticulocytes
      increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating
      a probable higher reticulocyte release and/or production despite decreased serum
      erythropoietin (EPO) concentrations (-46%, P<0.01). Hormones (thyroid,
      catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and
      haptoglobin) and renal function (creatinine, renal, osmolar and free-water
      clearances) did not significantly vary (except for lower thyroid stimulating
      hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG)
      increased throughout HH on return (+14.7%, P<0.05) and an inverse linear
      relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn
      only ( r=-0.66, P<0.03). Inverse linear relationships were also found between
      C(a)O(2) and EPO at the end of HH before ( r=-0.63, P<0.05) and after the sojourn
      ( r=-0.60, P=0.05) with identical slopes but different ordinates at the origin,
      suggesting that the sensitivity but not the gain of the EPO response to hypoxia
      was modified by altitude acclimatization. Higher 2,3-DPG levels could partly
      explain this decreased sensitivity of the EPO response to hypoxia. In conclusion,
      we show that altitude acclimatization modifies the control of erythropoiesis not
      only at sea level, but also during a subsequent hypoxia.

PMID- 15248068
TI  - Effects of aerobic endurance training status and specificity on oxygen uptake
      kinetics during maximal exercise.
AB  - The main purpose of this study was to analyze the effects of exercise mode,
      training status and specificity on the oxygen uptake (V(.)O(2)) kinetics during
      maximal exercise performed in treadmill running and cycle ergometry. Seven
      runners (R), nine cyclists (C), nine triathletes (T) and eleven untrained
      subjects (U), performed the following tests on different days on a motorized
      treadmill and on a cycle ergometer: (1) incremental tests in order to determine
      the maximal oxygen uptake (V(.)O(2max)) and the intensity associated with the
      achievement of V(.)O(2max) ( IV(.)O(2max)); and (2) constant work-rate running
      and cycling exercises to exhaustion at IV(.)O(2max) to determine the "effective"
      time constant of the V(.)O(2) response (tauV (.)O(2)). Values for V(.)O(2max)
      obtained on the treadmill and cycle ergometer [R=68.8 (6.3) and 62.0 (5.0);
      C=60.5 (8.0) and 67.6 (7.6); T=64.5 (4.8) and 61.0 (4.1); U=43.5 (7.0) and 36.7
      (5.6); respectively] were higher for the group with specific training in the
      modality. The U group showed the lowest values for V(.)O(2max), regardless of
      exercise mode. Differences in tau V(.)O(2) (seconds) were found only for the U
      group in relation to the trained groups [R=31.6 (10.5) and 40.9 (13.6); C=28.5
      (5.8) and 32.7 (5.7); T=32.5 (5.6) and 40.7 (7.5); U=52.7 (8.5) and 62.2 (15.3);
      for the treadmill and cycle ergometer, respectively]; no effects of exercise mode
      were found in any of the groups. It is concluded that tau V(.)O(2) during the
      exercise performed at IV(.)O(2max) is dependent on the training status, but not
      dependent on the exercise mode and specificity of training. Moreover, the
      transfer of the training effects on tau V(.)O(2) between both exercise modes may
      be higher compared with V(.)O(2max).

PMID- 15248069
TI  - Vitamin E supplementation, exercise and lipid peroxidation in human participants.
AB  - The theoretical benefits of using antioxidant vitamin supplements to quench
      oxygen free radicals appear large. The major function of vitamin E is to work as
      a chain-breaking antioxidant in a fat soluble environment so as to protect
      polyunsaturated fatty acids within membrane phospholipids and in plasma
      lipoproteins. The purpose of this critical review was to determine whether
      vitamin E supplementation decreases exercise-induced lipid peroxidation in
      humans. If vitamin E alone is ineffective, researchers can turn their efforts to
      other individual antioxidants or combinations. Using the search words "vitamin
      E", "exercise", "lipid peroxidation" and "antioxidant", all relevant studies
      since 1985 were identified through a computer search using Pub Med and Sport
      Discuss databases. Additional articles were reviewed from the reference list of
      the retrieved articles. Nine vitamin E studies met the criteria of using human
      participants in an experimental design. Studies were analyzed to determine the
      strength of evidence regarding the efficacy of vitamin E supplementation.
      Strength of evidence was based on: (1) number of participants, (2) intensity of
      the exercise test, (3) type of research design, (4) other controls, (5) the
      biomarker of lipid peroxidation, (6) the timing of the biomarker measurement, (7)
      measurement of vitamin E status and (8) correction for plasma volume change.
      Overall, the six studies showing no effect of vitamin E supplementation had a
      much higher total score (67) in comparison to the three studies showing positive
      effects (38). Although limitations have plagued much of the research, vitamin E
      supplementation does not appear to decrease exercise-induced lipid peroxidation
      in humans.

PMID- 15248071
TI  - Functional recovery of the plantarflexor muscle group after hindlimb unloading in
      the rat.
AB  - Research into skeletal muscle's response to hindlimb unloading (HU) of the rodent
      has focused on that of the markedly affected slow-twitch anti-gravity muscles
      (e.g., soleus). However, the ability of the animal to locomote following HU
      should be best determined by the in vivo functional properties of the muscle
      groups involved and, to our knowledge, this has not been investigated. Our
      objective was to determine how the in vivo functional properties of the rat ankle
      plantarflexor group change after 28 days of HU and during a subsequent 28-day
      recovery. Rats ( n=48) were unloaded for 28 days after which they were either
      tested immediately or allowed to recover for 7, 14, or 28 days before being
      tested. Control rats ( n=61) were tested at comparable times. In vivo functional
      properties of the ankle plantarflexors were assessed under anesthesia using an
      isokinetic dynamometer and included determination of the isometric torque
      frequency relationship, the concentric torque-ankle angular velocity
      relationship, and fatigability. Immediately after HU, plantarflexor muscle weight
      was reduced by 24% but isometric torque production was reduced by 7-9% only at >
      or =100 Hz and concentric torque production was not significantly affected.
      However, after 7 days of recovery, in vivo function was more adversely affected;
      isometric and concentric torques were reduced by 12-33% and 16-36%, respectively,
      relative to control levels. In vivo plantarflexor function was recovered by 14
      days. In conclusion, 28 days of HU has minor adverse effects on the in vivo
      function of the rat ankle plantarflexors. During the first week of recovery from
      HU, injury apparently occurs to the plantarflexors resulting in a transient
      impairment of functional capacity.

PMID- 15248073
TI  - Mitochondrial DNA control region sequences from Nairobi (Kenya): inferring
      phylogenetic parameters for the establishment of a forensic database.
AB  - Large forensic mtDNA databases which adhere to strict guidelines for generation
      and maintenance, are not available for many populations outside of the United
      States and western Europe. We have established a high quality mtDNA control
      region sequence database for urban Nairobi as both a reference database for
      forensic investigations, and as a tool to examine the genetic variation of Kenyan
      sequences in the context of known African variation. The Nairobi sequences
      exhibited high variation and a low random match probability, indicating utility
      for forensic testing. Haplogroup identification and frequencies were compared
      with those reported from other published studies on African, or African-origin
      populations from Mozambique, Sierra Leone, and the United States, and suggest
      significant differences in the mtDNA compositions of the various populations. The
      quality of the sequence data in our study was investigated and supported using
      phylogenetic measures. Our data demonstrate the diversity and distinctiveness of
      African populations, and underline the importance of establishing additional
      forensic mtDNA databases of indigenous African populations.

PMID- 15248072
TI  - Oxidative stress in the placenta.
AB  - Pregnancy is a state of oxidative stress arising from increased placental
      mitochondrial activity and production of reactive oxygen species (ROS), mainly
      superoxide anion. The placenta also produces other ROS including nitric oxide,
      carbon monoxide, and peroxynitrite which have pronounced effects on placental
      function including trophoblast proliferation and differentiation and vascular
      reactivity. Excessive production of ROS may occur at certain windows in placental
      development and in pathologic pregnancies, such as those complicated by
      preeclampsia and/or IUGR, overpowering antioxidant defenses with deleterious
      outcome. In the first trimester, establishment of blood flow into the
      intervillous space is associated with a burst of oxidative stress. The inability
      to mount an effective antioxidant defense against this results in early pregnancy
      loss. In late gestation increased oxidative stress is seen in pregnancies
      complicated by diabetes, IUGR, and preeclampsia in association with increased
      trophoblast apoptosis and deportation and altered placental vascular reactivity.
      Evidence for this oxidative stress includes increased lipid peroxides and
      isoprostanes and decreased expression and activity of antioxidants. The
      interaction of nitric oxide and superoxide produces peroxynitrite, a powerful
      prooxidant with diverse deleterious effects including nitration of tyrosine
      residues on proteins thus altering function. Nitrative stress, subsequent to
      oxidative stress is seen in the placenta in preeclampsia and diabetes in
      association with altered placental function.

PMID- 15248074
TI  - DXS10011: studies on structure, allele distribution in three populations and
      genetic linkage to further q-telomeric chromosome X markers.
AB  - The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker
      for forensic purposes. Investigation of this STR led to an allele nomenclature
      which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28
      and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB
      and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting
      some structural variants within alleles of identical length. Two types of repeat
      structure (regular and inter-alleles) are known and described as types A and B.
      Two SNPs which are in strong linkage disequilibrium to the different sequence
      types were found in the repeat flanking region. The type A sequence consists of a
      long stretch of uninterrupted homogenous repeats which is highly susceptible to
      slippage mutation during male meiosis.

PMID- 15248075
TI  - Cocaine found in a child's hair due to environmental exposure?
AB  - We report a case of a 6-year-old boy who had been living with his parents, both
      cocaine smokers, and who was urgently admitted to hospital for general distress.
      Upon examination, cocaine and cocaine metabolites were detected in hair and urine
      samples. These toxicological findings most likely indicate that the child had
      passively consumed the drug when living in a heavily contaminated environment.

PMID- 15248076
TI  - Chronic haematoma or soft-tissue neoplasm? A diagnostic dilemma.
AB  - Chronic soft-tissue haematomas are infrequently reported in the literature. We
      present a case of a slowly expanding post-traumatic chronic soft-tissue haematoma
      located anterior to the knee and leg, occurring in a region previously
      unreported. Both clinically and radiologically, it was impossible to distinguish
      the haematoma from an aggressive soft-tissue neoplasm. We review the literature
      and discuss the diagnostic problems related to this uncommon presentation.

PMID- 15248077
TI  - Pelviureteric junction obstruction as sequelae of Kawasaki disease.
AB  - We present a 7-year-old boy who was admitted with a history of cough for a week,
      neck pain with associated swelling for 4 days, fever, and vague periumbilical
      pain. He was diagnosed with Kawasaki disease, and subsequently developed
      vasculitis of the ureter and stricture of the ureteric lumen at the level of the
      pelviureteric junction.

PMID- 15248078
TI  - Anaesthesia for conjoined twins.
AB  - INTRODUCTION: Anaesthesia for conjoined twin surgery, whether prior to or for
      separation, is an enormous challenge to the paediatric anaesthesiologist.
      DISCUSSION: The site and complexity of the conjunction will affect airway
      management, acquisition of vascular access, the extent of blood loss, and the
      number of surgical specialties involved. Preoperative assessment and planning,
      with interdisciplinary communication and cooperation, is vital to the success of
      the operations. These twins require a dedicated team of anaesthetists for each
      child, and, consequently, duplication of all monitoring and equipment in one
      operating room is necessary. Meticulous attention to detail, monitoring, and
      vigilance are mandatory. Planning for the postoperative period in the intensive
      care unit (ICU), as well as the babies' reconstruction and rehabilitation, is
      essential from the time of the initial admission.

PMID- 15248079
TI  - [Subperiosteal orbital hemorrhage after heart surgery].
AB  - We report on a patient who suffered sudden diplopia after heart surgery. Computed
      tomography of the orbita revealed a subperiosteal hemorrhage as the underlying
      cause. We discuss possible mechanisms that may have led to the bleeding as well
      as therapeutic options.

PMID- 15248080
TI  - The influence of preoperative MRI of the breasts on recurrence rate in patients
      with breast cancer.
AB  - Preoperative MRI of the breasts has been proven to be the most sensitive imaging
      modality in the detection of multifocal or multicentric tumor manifestations as
      well as simultaneous contralateral breast cancer. The aim of the presented
      retrospective study was to evaluate the benefit of preoperative MRI for patients
      with breast cancer. Preoperative MRI performed in 121 patients (group A) were
      compared to 225 patients without preoperative MRI (group B). Patients of group A
      underwent contrast-enhanced MR imaging of the breast using a 2D FLASH sequence
      technique (TR/TE/FA 336 ms/5 ms/90 degrees; 32 slices of 4-mm thickness, time of
      acquisition 1:27 min, contrast agent dosage 0.1 mmol Gd-DTPA/kg bw). All patients
      had histologically verified breast cancer and follow-up for more than 20 months
      (mean time group A: 40.3 months, group B: 41 months). Both groups received the
      same types of systemic treatment after breast conserving surgery. The in-breast
      tumor recurrence rate in group A was 1/86 (1.2%) compared to 9/133 (6.8%) in
      group B. Contralateral carcinoma were detected within follow-up in 2/121 (1.7%)
      in group A vs. 9/225 (4%) in group B. All results were statistically significant
      (P<0.001). Based on these results, preoperative MRI of the breasts is recommended
      in patients with histopathologically verified breast cancer for local staging.

PMID- 15248081
TI  - Bipolar radiofrequency ablation in ex vivo bovine liver with the open-perfused
      system versus the cooled-wet system.
AB  - The aim of this study was to investigate the efficacy of bipolar radiofrequency
      ablation (RFA) with the open-perfused electrode and cooled-wet electrode. Bipolar
      RF was applied for 20 min to the ex vivo bovine liver using either the Berchtold
      system with two 16-gauge open-perfused electrodes (group A, n=15) or the
      Radionics system with two 15-gauge cooled-wet electrodes (group B, n=15). In both
      groups, two electrodes were placed 3 cm apart. The ablation zone was created by
      the RF energy delivered together with the infusion of 5% hypertonic saline (2
      ml/min). The dimension of the ablation zone, its shape and the changes in the
      impedance and W s of two groups during the RFA were examined and documented. The
      vertical diameter (Dv) along the probe, the long-axis diameter (Dl) perpendicular
      to the Dv in the longitudinal plane and the short-axis diameter of the ablation
      zone (Ds) in the transverse plane through the midpoint between the tips of two
      probes were measured. The mean accumulated energy output in the Radionics system
      was higher than in the Berchtold system (159,887.0+/-36,423 W s vs. 87,555.1+/
      86,787 W s). The difference was statistically significant (P<0.05). In group A,
      the impedance intermittently rose to above 700 Omega during the RFA in all
      sessions, which led to a gradual decrease of the power output to lower than 30 W.
      In group B, on the other hand, the impedance did not change markedly. The mean Dv
      value of the coagulation necrosis in group B was significantly longer than in
      group A (5.0+/-0.4 cm vs. 4.3+/-0.6 cm, P<0.05). The mean Dl and Ds were 6.7+/
      0.5 cm and 5.0+/-0.8 cm in group A, and 6.5+/-0.8 cm and 5.5+/-0.7 cm in group B,
      respectively (P>0.05). The data demonstrate that the cooled-wet electrode
      generates the more spherical ablation zone than the open-perfused electrode. With
      approximately doubled power output, the bipolar RFA with the cooled-wet
      electrodes induces a larger volume of tissue coagulation than with the open
      perfused electrodes.

PMID- 15248082
TI  - Small bowel perforation due to ingested clam valve: imaging findings.

PMID- 15248083
TI  - Taxonomic discrimination of flowering plants by multivariate analysis of Fourier
      transform infrared spectroscopy data.
AB  - Fourier transform infrared spectroscopy (FTIR) provides biochemical profiles
      containing overlapping signals from a majority of the compounds that are present
      when whole cells are analyzed. Leaf samples of seven higher plant species and
      varieties were subjected to FTIR to determine whether plants can be discriminated
      phylogenetically on the basis of biochemical profiles. A hierarchical dendrogram
      based on principal component analysis (PCA) of FTIR data showed relationships
      between plants that were in agreement with known plant taxonomy. Genetic
      programming (GP) analysis determined the top three to five biomarkers from FTIR
      data that discriminated plants at each hierarchical level of the dendrogram. Most
      biomarkers determined by GP analysis at each hierarchical level were specific to
      the carbohydrate fingerprint region (1,200-800 cm(-1)) of the FTIR spectrum. Our
      results indicate that differences in cell-wall composition and structure can
      provide the basis for chemotaxonomy of flowering plants.

PMID- 15248084
TI  - Introduction of a citrus blight-associated gene into Carrizo citrange [Citrus
      sinensis (L.) Osbc. x Poncirus trifoliata (L.) Raf.] by Agrobacterium-mediated
      transformation.
AB  - The protein p12 accumulates in leaves of trees with citrus blight (CB), a serious
      decline of unknown cause. The function of p12 is not known, but sequence analysis
      indicates it may be related to expansins. In studies to determine the function of
      p12, sense and antisense constructs were used to make transgenic Carrizo citrange
      using an Agrobacterium-mediated transformation system. Homogeneous beta
      glucuronidase+ (GUS+) sense and antisense transgenic shoots were regenerated
      using kanamycin as a selective agent. Twenty-five sense and 45 antisense
      transgenic shoots were in vivo grafted onto Carrizo citrange for further
      analyses. In addition, 20 sense and 18 antisense shoots were rooted. The
      homogeneous GUS+ plants contained either the p12 sense or antisense gene (without
      the intron associated with the gene in untransformed citrus) as shown by PCR and
      Southern blotting. Northern blots showed the expected RNA in the sense and
      antisense plants. A protein of identical size and immunoreactivity was observed
      in seven of nine sense plants but not in nine antisense or non-transgenic plants.
      At the current stage of growth, there are no visual phenotypic differences
      between the transgenic and non-transgenic plants. Selected plants will be budded
      with sweet orange for field evaluation for resistance or susceptibility to CB and
      general rootstock performance.

PMID- 15248085
TI  - The Turkish versions of the Bath Ankylosing Spondylitis and Dougados Functional
      Indices: reliability and validity.
AB  - OBJECTIVE: The aim of this study was to develop a Turkish version of the Bath
      Ankylosing Spondylitis Functional Index (BASFI) and Dougados Functional Index
      (DFI) and assess their reliability, validity, and sensitivity to change. METHODS:
      The Turkish versions of the BASFI and DFI were obtained after a translation and
      back-translation process. Seventy-one patients with ankylosing spondylitis (AS)
      were included in the study. For investigation of the reliability of the BASFI and
      DFI, 36 of the patients recompleted both indices on the following day. To assess
      validity, the patients were evaluated with the Bath AS Disease Activity Index
      (BASDAI), Bath AS Metrology Index (BASMI), Bath AS Patient Global Score (BAS-G),
      physicians' assessment of disease activity, Bath AS Radiology Index-spine (BASRI
      s) and sacroiliac joints, erythrocyte sedimentation rate (ESR), and C-reactive
      protein (CRP). To assess the sensitivity to change, 16 patients were included in
      an 8-week home exercise program. In addition, 16 who had been on nonsteroidal
      anti-inflammatory drug (NSAID) treatment were requested to stop the treatment for
      1 to 2 weeks. RESULTS: There were no significant differences in BASFI and DFI
      scores on two occasions within 24 h (P>0.05). The results showed correlations
      between both of the functional indices and the aforementioned validation
      parameters except ESR, CRP, and radiologic changes in the sacroiliac joints. The
      BASFI and DFI scores and BASMI and BASDAI values showed significant improvements
      in the home-exercise group. For the group of patients whose NSAIDs were stopped,
      BASFI, DFI, and BASDAI scores showed significant increase, whereas the mean BASMI
      score did not change. CONCLUSION: The results indicate that the Turkish versions
      of the BASFI and DFI are reliable, valid, and sensitive to change.

PMID- 15248086
TI  - Intrapopulation differences in ant eating in the mountain gorillas of Bwindi
      Impenetrable National Park, Uganda.
AB  - Variability in ant eating has been observed in several populations of eastern and
      western gorillas. We investigated the occurrence of ant (Dorylus sp.) eating in
      two groups of mountain gorillas (Gorilla beringei beringei) with overlapping home
      ranges within Bwindi Impenetrable National Park, Uganda from September 2001 to
      August 2002. We calculated the frequency of ant eating by an indirect method of
      analyzing fecal samples from silverbacks, adult females, and juveniles. One group
      consumed ants significantly more often than the other (3.3 vs 17.6% of days
      sampled). Furthermore, the group that consumed ants more often also consumed them
      on a seasonal basis (September-February monthly range: 0-8%; March-August monthly
      range: 30-42.9%). Finally, females and juveniles of this group consumed ants
      significantly more often than did the silverback (total samples containing ants:
      silverback, 2.1%; adult female, 13.2%; juvenile, 11.2%). Differences in ant
      eating between groups are likely due to variability in use of habitats where ants
      occur (particularly secondary forests). Surveys of ant densities in differing
      habitats, nutritional analysis of ants, and quantification of the amount of ants
      in their diets are necessary to understand if ant consumption is due to
      availability, nutritional value, group traditions, or taste preference.

PMID- 15248087
TI  - Analysis of infant carrying in large, well-established family groups of captive
      marmosets (Callithrix jacchus).
AB  - To assess the pattern of infant carrying across time and family members, we
      counted which animals in 13 well-established family groups of captive-bred
      marmosets (Callithrix jacchus) carried neonates during the first 8 weeks of life.
      The neonates were carried almost continuously for the first 3 weeks and then
      spent progressively more time independently. The mother did most of the carrying
      for the first 2 weeks, her contribution rising from day 1 to day 3 and declining
      thereafter. The contribution of the father was high on day 1, declined during the
      first week, and then rose to a peak in the fourth week. The contribution of the
      siblings rose sharply during the first week and declined thereafter. There was no
      overall difference in amount of infant carrying by each parent. The contribution
      of each sibling was small although in these large families the total contribution
      by siblings was large. These data may differ from previous observations because
      the breeding pairs were very well established, the families were large, and all
      except the youngest animals were very experienced in rearing and carrying. These
      data emphasise the group-dynamic nature of infant carrying in a primate species.

PMID- 15248088
TI  - Encoding microbial metabolic logic: predicting biodegradation.
AB  - Prediction of microbial metabolism is important for annotating genome sequences
      and for understanding the fate of chemicals in the environment. A metabolic
      pathway prediction system (PPS) has been developed that is freely available on
      the world wide web (http://umbbd.ahc.umn.edu/predict/), recognizes the organic
      functional groups found in a compound, and predicts transformations based on
      metabolic rules. These rules are designed largely by examining reactions
      catalogued in the University of Minnesota Biocatalysis/Biodegradation Database
      (UM-BBD) and are generalized based on metabolic logic. The predictive accuracy of
      the PPS was tested: (1) using a 113-member set of compounds found in the
      database, (2) against a set of compounds whose metabolism was predicted by human
      experts, and (3) for consistency with experimental microbial growth studies.
      First, the system correctly predicted known metabolism for 111 of the 113
      compounds containing C and H, O, N, S, P and/or halides that initiate existing
      pathways in the database, and also correctly predicted 410 of the 569 known
      pathway branches for these compounds. Second, computer predictions were compared
      to predictions by human experts for biodegradation of six compounds whose
      metabolism was not described in the literature. Third, the system predicted
      reactions liberating ammonia from three organonitrogen compounds, consistent with
      laboratory experiments showing that each compound served as the sole nitrogen
      source supporting microbial growth. The rule-based nature of the PPS makes it
      transparent, expandable, and adaptable.

PMID- 15248089
TI  - Fusion of Bacillus stearothermophilus leucine aminopeptidase II with the raw
      starch-binding domain of Bacillus sp. strain TS-23 alpha-amylase generates a
      chimeric enzyme with enhanced thermostability and catalytic activity.
AB  - Bacillus stearothermophilus leucine aminopeptidase II (LAPII) was fused at its C
      terminal end with the raw-starch-binding domain of Bacillus sp. strain TS-23
      alpha-amylase. The chimeric enzyme (LAPsbd), with an apparent molecular mass of
      approximately 61 kDa, was overexpressed in IPTG-induced Escherichia coli cells
      and purified to homogeneity by nickel-chelate chromatography. The purified enzyme
      retained LAP activity and adsorbed raw starch. LAPsbd was stable at 70 degrees C
      for 10 min, while the activity of wild-type enzyme was completely abolished under
      the same environmental condition. Compared with the wild-type enzyme, the twofold
      increase in the catalytic efficiency for LAPsbd was due to a 218% increase in the
      k(cat) value.

PMID- 15248090
TI  - Ram horn peptone as a source of citric acid production by Aspergillus niger, with
      a process.
AB  - The present study deals with the production of citric acid from a ram horn
      peptone (RHP) by Aspergillus niger NRRL 330. A medium from RHP and a control
      medium (CM) were compared for citric acid production using A. niger in a batch
      culture. For this purpose, first, RHP was produced. Ram horns were hydrolyzed by
      treatment with acids (6 N H(2)SO(4), 6 N HCl) and neutralizing solutions. The
      amounts of protein, nitrogen, ash, some minerals, total sugars, total lipids and
      amino acids of the RHP were determined. RHP was compared with peptones with a
      bacto-tryptone from casein and other peptones. The results from RHP were similar
      to those of standard peptones. The optimal concentration of RHP for the
      production of citric acid was found to be 4% (w/w). A medium prepared from 4% RHP
      was termed ram horn peptone medium (RHPM). In comparison with CM, the content of
      citric acid in RHPM broth (84 g/l) over 6 days was 35% higher than that in CM
      broth (62 g/l). These results show that citric acid can be produced efficiently
      by A. niger from ram horn.

PMID- 15248091
TI  - Treatment of adenovirus infections in the immunocompromised host.
AB  - Adenovirus infections are increasing as causes of morbidity and mortality in
      severely immunocompromised patients. The currently available antiviral agents,
      ribavirin and cidofovir, have yielded mixed results in case reports and small
      case series. Similar to cytomegalovirus disease, established adenovirus disease
      is often difficult to treat. Therapy may yield poor results, even when effective
      antiviral drugs are used. New strategies, including pre-emptive therapy, should
      be tested in prospective, clinical trials. New agents and adoptive transfer of
      specific T-cells to adenovirus might improve the current situation.

PMID- 15248092
TI  - A new confirmatory Neisseria gonorrhoeae real-time PCR assay targeting the porA
      pseudogene.
AB  - The Roche Cobas Amplicor system is widely used for the detection of Neisseria
      gonorrhoeae but is known to cross react with some commensal Neisseria spp.
      Therefore, a confirmatory test is required. The most common target for
      confirmatory tests is the cppB gene of N. gonorrhoeae. However, the cppB gene is
      also present in other Neisseria spp. and is absent in some N. gonorrhoeae
      isolates. As a result, laboratories targeting this gene run the risk of obtaining
      both false-positive and false-negative results. In the study presented here, a
      newly developed N. gonorrhoeae LightCycler assay (NGpapLC) targeting the N.
      gonorrhoeae porA pseudogene was tested. The NGpapLC assay was used to test 282
      clinical samples, and the results were compared to those obtained using a testing
      algorithm combining the Cobas Amplicor System (Roche Diagnostics, Sydney,
      Australia) and an in-house LightCycler assay targeting the cppB gene (cppB-LC).
      In addition, the specificity of the NGpapLC assay was investigated by testing a
      broad panel of bacteria including isolates of several Neisseria spp. The NGpapLC
      assay proved to have comparable clinical sensitivity to the cppB-LC assay. In
      addition, testing of the bacterial panel showed the NGpapLC assay to be highly
      specific for N. gonorrhoeae DNA. The results of this study show the NGpapLC assay
      is a suitable alternative to the cppB-LC assay for confirmation of N. gonorrhoeae
      positive results obtained with Cobas Amplicor.

PMID- 15248094
TI  - Preliminary observations of tool use in captive hyacinth macaws (Anodorhynchus
      hyacinthinus).
AB  - Many animals use tools (detached objects applied to another object to produce an
      alteration in shape, position, or structure) in foraging, for instance, to access
      encapsulated food. Descriptions of tool use by hyacinth macaws (Anodorhynchus
      hyacinthinus) are scarce and brief. In order to describe one case of such
      behavior, six captive birds were observed while feeding. Differences in nut
      manipulation and opening proficiency between adults and juveniles were recorded.
      The tools may be serving as a wedge, preventing the nut from slipping and/or
      rotating, reducing the impact of opening, or providing mechanical aid in its
      positioning and/or use of force. Data suggest that birds of this species have an
      innate tendency to use objects (tools) as aids during nut manipulation and
      opening.

PMID- 15248093
TI  - Two cases of severe phototoxic reactions related to long-term outpatient
      treatment with voriconazole.

PMID- 15248096
TI  - D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings:
      coincidence, or linked disorders?
AB  - Glutaric aciduria type 1 (GA1) and D-2-hydroxyglutaric aciduria ( D-2-HGA) are
      cerebral organic acidurias characterized by the excretion of 3-hydroxyglutaric
      and D-2-hydroxyglutaric acids, respectively. GA1 is caused by a deficiency of
      glutaryl-CoA dehydrogenase encoded by the GCDH gene; the biochemical and genetic
      basis of D-2-HGA is unknown. We diagnosed GA1 in the son of consanguineous
      Palestinian parents, and D-2-HGA in his sister and brother. All three siblings
      were neurologically and developmentally normal. A small but abnormal increase in
      excretion of D-2-hydroxyglutaric acid was also found in the sibling with GA1.
      These observations suggested a possible pathophysiological link between these two
      disorders. The sibling with GA1 was homozygous whilst his siblings with D-2-HGA
      were heterozygous for a 1283 C>T missense mutation (T416I) in exon 11 of the GCDH
      gene. However, sequence analysis of the GCDH gene in 8 additional unrelated
      patients with D-2-HGA and 3 with combined D/ L-2-HGA did not reveal any
      pathogenic mutations. The biochemical and genetic basis of D-2-HGA remains to be
      determined.

PMID- 15248095
TI  - Intragenic modifiers of hereditary spastic paraplegia due to spastin gene
      mutations.
AB  - Hereditary spastic paraplegia (HSP) is a genetically heterogeneous
      neurodegenerative disease characterized by wide variability in phenotypic
      expression, both within and among families. The most-common cause of autosomal
      dominant HSP is mutation of the gene encoding spastin, a protein of uncertain
      function. We report the existence of intragenic polymorphisms of spastin that
      modify the HSP phenotype. One (S44L) is a previously described recessively acting
      allele and the second is a novel allele affecting the adjacent amino acid residue
      (P45Q). In 4 HSP families in which either L44 or Q45 segregates independently of
      a missense or splicing mutation in the AAA domain of spastin, L44 and Q45 are
      each associated with a striking decrease in age at onset in the presence of the
      AAA domain mutations. Using a bioinformatics approach, we found that the highly
      conserved S44 is predicted to be phosphorylated by a number of family members of
      the proline-directed serine/threonine cyclin-dependent kinases (Cdks). Cdk1 and
      Cdk5 showed no kinase activity toward synthetic spastin peptide in an in vitro
      kinase assay, suggesting that this serine residue may be phosphorylated by a
      different Cdk. Our identification of S44L and P45Q as modifiers of the HSP
      phenotype suggests a role for spastin phosphorylation by Cdks in the
      neurodegeneration of the most-common form of HSP.

PMID- 15248097
TI  - Agenesis of the corpus callosum, abnormal genitalia and intractable epilepsy due
      to a novel familial mutation in the Aristaless-related homeobox gene.
AB  - Mutations in the Aristaless-related homeobox (ARX) gene are associated with a
      broad spectrum of disorders including X-linked lissencephaly with abnormal
      genitalia (XLAG) and absent corpus callosum. Here, we describe a family with two
      male infants suffering from agenesis of the corpus callosum (ACC), intractable
      epilepsy, and abnormal genitalia. The phenotype of both affected patients
      differed in severity of the cerebral malformation with one showing no obvious
      evidence for lissencephaly. Both infants lacked any psychomotor development and
      died at the age of 17 weeks and 18 months, respectively. Genetic analysis of the
      ARX gene revealed a novel frameshift mutation in exon 4 (nt1419_1420insAC)
      leading to a shortened protein lacking the aristaless domain. In summary,
      analysis of the ARX gene should not only be considered in male patients with
      typical features of XLAG but also in those presenting with early onset epilepsy,
      ACC, and abnormal genitalia without obvious neuroradiological features of
      lissencephaly.

PMID- 15248098
TI  - Electroencephalographic aspects of periventricular hemorrhagic infarction in
      preterm infants.
AB  - The aim of this study was to investigate electroencephalographic aspects of
      periventricular hemorrhagic infarction (PVHI) in preterm infants. The subjects
      were 11 preterm infants with PVHI, who were admitted to the Neonatal Intensive
      Care Unit of Anjo Kosei Hospital from April 1985 through December 1997. The
      patients underwent serial cranial ultrasonography and were diagnosed as having
      PVHI. An EEG was recorded at least once within 1 week after PVHI and then
      recorded at 1- to 4-week intervals until 40 weeks of postconceptional age. The
      EEG findings were classified into acute and chronic stage abnormalities. Acute
      stage EEG abnormalities were seen in 5 infants after PVHI, which were symmetrical
      in all infants. Among them, 3 infants died during the early neonatal period. The
      infants who had a higher grade of acute stage EEG abnormalities showed
      significantly higher mortality. Among the surviving 8 infants, chronic stage EEG
      abnormalities were seen in 3 predominantly in the ipsilateral side of PVHI, and
      all of them developed hemiplegia. The sensitivity and specificity of chronic
      stage EEG abnormalities to predict outcome were 0.75 and 1.0, respectively. Acute
      and chronic stage EEG abnormalities give valuable information for short-term and
      long-term outcome in preterm infants with PVHI.

PMID- 15248099
TI  - Clinical presentations of patients with polyol abnormalities.
AB  - Since our description of a patient with leukoencephalopathy and highly elevated
      polyols in the brain and body fluids, we started screening for polyol
      abnormalities in patients highly suspected of a metabolic disorder. We identified
      four additional patients with consistent abnormalities in sugar and polyol
      profiles in body fluids. The clinical, neuroimaging, and biochemical findings of
      the five patients detected so far are described in the present paper. In four
      patients neurological problems dominated the clinical picture, whereas liver
      failure dominated in the other patient. The sugar and polyol profiles were
      abnormal in body fluids in all patients, but the profiles were different in
      individual patients. A deficiency of transaldolase was found in the patient
      presenting with liver failure. We were not able to identify the basic defect in
      the four patients with predominantly neurological problems. The differences in
      clinical picture, MRI abnormalities, and sugar and polyol profiles in these
      patients suggest that the underlying defects may be different. Whether the
      abnormal sugar and polyol profiles are directly related to the cause of disease
      via defects in polyol metabolism or transport remains to be elucidated.

PMID- 15248100
TI  - Long-term observations of patients with infantile spinal muscular atrophy with
      respiratory distress type 1 (SMARD1).
AB  - We describe 6 unrelated patients affected by infantile spinal muscular atrophy
      with respiratory distress type 1 (SMARD1) with prolonged survival upon mechanical
      ventilation (4.5-11 years), which has not been reported before. Biallelic
      mutations in the IGHMBP2 gene proved the diagnosis of SMARD1 in all patients.
      Disease onset was in the first 2 months in the described patients, starting with
      generalised hypotonia, failure to thrive, and early breathing difficulties.
      Diaphragmatic palsy was diagnosed and permanent ventilation was initiated 2-8
      months after onset. Within months a more distal muscular atrophy became evident
      associated with joint contractures (talipes), hand drops, and fatty finger pads.
      Motor development remained minimal, loss of function was observed within the
      first year after which no further progression was recorded. Voiding dysfunction
      with reflux nephropathy was observed in 3 patients and has not been reported
      before. Further evidence of autonomic nerve dysfunction resulting in cardiac
      arrhythmia, hypertension, and excessive sweating was given in 2 patients.
      Investigative results were largely compatible with those obtained in classic SMA.
      However, neurogenic atrophy muscle was more pronounced in distal muscles, if
      examined, and there was evidence of peripheral nerve involvement at least in some
      patients.

PMID- 15248101
TI  - Synaptic congenital myasthenic syndrome in three patients due to a novel missense
      mutation (T441A) of the COLQ gene.
AB  - Congenital myasthenic syndromes (CMS) with deficiency of endplate
      acetylcholinesterase (AChE) are caused by mutations in the synapse specific
      collagenic tail subunit gene (COLQ) of AChE. We identified a novel missense
      mutation (T441A) homozygously in three CMS patients from two unrelated German
      families. The mutation is located in the C-terminal region of the ColQ protein,
      which initiates assembly of the triple helix, and is essential for insertion of
      the tail subunit into the basal lamina. Density gradient analysis of AChE
      extracted from muscle of one of the patients revealed the absence of asymmetric
      AChE. All patients were characterized by an onset of disease in childhood,
      exercise-induced proximal weakness, absence of ptosis and ophthalmoparesis, a
      decremental EMG response, and deterioration in response to anticholinesterase
      drugs. However, age at onset, disease progression, disease severity, and
      functional impairment varied considerably among the three patients. As adults,
      two siblings from one family experience only mild impairment, while the third
      patient requires a wheelchair for most of the day and assisted ventilation at
      night.

PMID- 15248102
TI  - MRI findings in pediatric neuro-Behcet's disease.
AB  - Behcet's disease (BD), a systemic vasculitis of unknown cause, affects many
      organs and systems. Neurological involvement is seen in 5-15% of the patients,
      and the two major forms of neurological disease seen in BD are central nervous
      system (CNS) parenchymal involvement and cerebral venous sinus thrombosis. We
      report a 14-year-old boy with BD who had neuro-parenchymal involvement. The
      diagnosis of the systemic disease was not made until the onset of the
      neurological manifestations, which led to an MRI study that revealed findings
      suggestive of CNS involvement of BD. We therefore emphasize the importance of the
      localization and appearance of other characteristics of the lesions on MRI in the
      differential diagnosis of parenchymal neuro-Behcet syndrome.

PMID- 15248103
TI  - Facial hemangioma, and associated malformations: a case report.
AB  - Facial hemangioma can be isolated lesions or associated with a wide variety of
      systemic findings. We report a 9-month-old girl who shows an extensive facial
      hemangioma, intracranial and extracranial vascular malformations, a Dandy-Walker
      malformation and congenital cardiac malformations. This patient serves as an
      ample reason why children with similar cutaneous lesions should be carefully
      evaluated for other associated defects.

PMID- 15248104
TI  - Neuromyelitis optica in a child with atypical onset and severe outcome.
AB  - We report on a seven-year-old boy with inflammatory relapsing-remitting CNS
      disease, involving the optic nerves and spinal cord, with increasingly severe
      sequelae after each relapse. Clinical course, neuroimaging and laboratory
      findings were consistent with neuromyelitis optica. Biopsy of leptomeninges and
      underlying nervous tissue showed increased vascularization and thickened
      hyalinized vessel walls, reported as suggestive for neuromyelitis optica.
      Clinical features at onset were atypical, rendering the case highly unusual and
      the diagnosis tentative.

PMID- 15248105
TI  - X-linked lissencephaly with abnormal genitalia associated with renal phosphate
      wasting.
AB  - X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused
      by mutations in the aristaless-related homeobox (ARX) gene. We report on the
      clinical data of a boy with a 1-bp deletion (790 delC) resulting in a frame shift
      in the ARX gene and prolonged survival until age 18 months. Similar to other
      patients, the boy showed postnatal microcephaly, hypothalamic dysfunction,
      intractable neonatal seizures, and chronic diarrhoea. In addition, he suffered
      from exocrine pancreatic insufficiency and renal phosphate wasting became
      apparent from age 5 months, both of which have not been described previously in
      XLAG. This allows us to speculate that the phenotype of XLAG is more complex than
      hitherto known and may include renal phosphate wasting which might not have been
      observed in other patients due to early death.

PMID- 15248106
TI  - Conjugated bile acid replacement therapy in short bowel syndrome patients with a
      residual colon.
AB  - AIM: To test the efficacy of cholylsarcosine (synthetic conjugated bile acid) and
      ox bile extracts (mixture of natural conjugated bile acids) on fat absorption,
      diarrhea, and nutritional state in four short bowel syndrome (SBS) patients with
      a residual colon not requiring parenteral alimentation. METHODS: The effect of
      cholylsarcosine (2 g/meal) on steatorrhea and diarrhea was examined in short-term
      balance studies with a constant fat intake in all four patients. The effect of
      continuous cholylsarcosine ingestion on nutritional state was assessed by changes
      in body weight in three patients. In two patients, the effects of cholylsarcosine
      were compared with those of ox bile extracts. Because of the low incidence rate
      of SBS this is not a controlled study. RESULTS: In balance studies,
      cholylsarcosine increased fat absorption from 65.5 to 94.5 g/day (a 44 %
      increment), an energy gain of 261 kcal/d. Fecal weight increased by 26 %. In two
      patients natural conjugated bile acids also reduced steatorrhea, but greatly
      increased diarrhea. As outpatients consuming an unrestricted diet and ingesting
      cholylsarcosine, three patients gained weight at an average rate of 0.9 kg/week
      without worsening of diarrheal symptoms. CONCLUSIONS: Cholylsarcosine is
      efficacious and safe for enhancing fat absorption and nutritional status in short
      bowel syndrome patients with residual colon. Natural conjugated bile acids
      improve steatorrhea to a smaller extent and greatly worsen diarrhea.

PMID- 15248107
TI  - [Effectiveness and patient tolerance of screening colonoscopy -- first results].
AB  - BACKGROUND: In Germany screening colonoscopy was introduced into the national
      program on colorectal cancer prevention in October 2002 for asymptomatic subjects
      older than 55 years. It is the aim of this program to reduce the rate of
      mortality of colorectal cancer (CRC) during the next decade. Up to now no data
      are available concerning the outcome and patient tolerance of screening
      colonoscopy. METHODS: Patients were enrolled in the prospective study between
      October 2002 and June 2003. The diagnoses from colonoscopy and complications were
      recorded. A short interview provided information on individual family risks of
      CRC. During June 2003 all subjects were handed a questionnaire to evaluate their
      satisfaction and tolerance concerning screening colonoscopy. All subjects were
      offered sedation (Disoprivan: Propofol). RESULTS: A total of 1117 subjects (776
      [69.5 %] female, 341 [30.5 %] male) underwent screening colonoscopy; age: 64.3 +/
      6.9 years. 1104 (98.8 %) requested sedation. In 1090 cases (97.6 %) colonoscopy
      was completed to the cecum (photographic documentation of cecal landmarks). A
      total of 11 patients had invasive cancer (1 %), 4 of these had adenomas
      containing invasive carcinoma. The stage was T1/N0 or T2/N0. A total of 138 (12.4
      %) patients had 168 polypoid lesions, which were treated by complete polypectomy.
      402 small polypoid lesions (< 0.5 cm) were only detected by biopsy. In this group
      233 adenomas (20.9 %) were found. Complications were: 1 perforation and 4
      haemorrhages after polypectomy. Patient tolerance was very high. 99.4 % of all
      subjects agreed to a control colonoscopy or recommended screening colonoscopy to
      their relatives and friends. CONCLUSION: Screening colonoscopy is an effective
      and well-accepted method in our unit for gastroenterology. The high prevalence of
      adenoma and invasive carcinoma suggests that screening colonoscopy should be
      provided for all persons at the age of 55, especially for men.

PMID- 15248108
TI  - [Diarrhea and weight loss in common variable immunodeficiency].
AB  - A 25-year-old male was hospitalized for diarrhea and weight loss. Since childhood
      he had experienced recurrent episodes of pneumonia and diarrhea. Physical and
      laboratory findings were compatible with malabsorption. On endoscopy, nodular
      lymphoid hyperplasia (NLH) of the small intestine was found. Common variable
      immunodeficiency syndrome (CVID) was suspected and diagnosis was established by
      demonstrating a significant reduction of plasma gamma-globulin levels.
      Immediately after starting immunoglobulin treatment diarrhea stopped, and both
      incidence and severity of pulmonary infections were significantly reduced, while
      recurrent gastrointestinal infections (notably lambliasis and Campylobacter
      infections) continued to occur and both bronchiectases and splenomegaly were
      progressive over years. This case report focuses on CVID as a potential
      underlying cause of diarrhea. The most important complications of the disease are
      presented. Therapeutical options are discussed in the light of recently published
      data.

PMID- 15248109
TI  - Ileocolic anastomotic ulcer after surgery in adulthood: case report and review of
      the literature.
AB  - Anastomotic ulcer is a rare complication after ileocolic resection, especially in
      adults without evidence of inflammatory bowel disease or tumor recurrence. We
      report the case of a 63-year-old male patient who presented 6 years after
      ileocolic resection, and also review the data of six similar cases described in
      the literature. The markedly reduced bile acid absorption found in our case
      raises the possibility of an etiological role of bile acids in the development of
      ileocolic anastomotic ulcers.

PMID- 15248110
TI  - [Endoscopic mucosal resection for early esophageal cancer with esophageal
      varices].
AB  - Squamous cell carcinomas account for more than 80 % of esophageal malignancies in
      Germany. Alcohol and tobacco smoke are two of the most important risk factors. In
      superficial esophageal squamous cell carcinoma, endoscopic mucosal resection
      (EMR) is a very useful and effective treatment modality. However, in patients
      with submucosal esophageal cancer, radical esophageal resection is regarded as
      the gold standard for treatment at present. We report the case of a 71-year-old
      female patient with alcohol-induced liver cirrhosis with esophageal varices and a
      - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic
      therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective
      treatment modality due to its limited penetration depth (< 2 mm) and the liver
      toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed
      to be associated with a high risk of bleeding due to the esophageal varices.
      Furthermore, this sensitizer is associated with a high rate of strictures and a
      long-lasting skin sensitivity. In contrast, arguments against an endoscopic
      mucosal resection (EMR) were endosonographically suspected submucosal tumor
      growth and a high risk of bleeding. Nevertheless, with respect to the lack
      alternatives we decided to perform an EMR after ligation of esophageal varices.
      The tumor could be resected in sano without major bleeding complication.
      Histology demonstrated a carcinoma in situ without submucosal invasion. After 3
      months a second EMR was necessary due to recurrence. Meanwhile after a follow-up
      period of 18 months only low grade intraepithelial neoplasia without
      macroscopically suspicious lesions was observed.

PMID- 15248111
TI  - [Current diagnosis and therapy of esophageal carcinoma].
AB  - In Germany the incidence of esophageal cancer is 6 - 10 per 100,000. At the time
      of diagnosis about 75 % of the patients suffer from UICC stage III or IV
      esophageal cancer. Less than 10 % of patients are diagnosed with early (T1)
      cancer. Diagnosis and staging relies on esophagoscopy including biopsies,
      endoscopic ultrasonography, and computerized tomography of the chest and abdomen.
      Intramucosal early cancer (T1a) and high-grade dysplasia can be treated either by
      surgery or by endoscopic mucosal resection. Chemoradiation is the definitive
      treatment of choice for localized squamous cell cancer of the proximal esophagus.
      As far as overall survival is concerned definitive chemoradiation is not inferior
      to esophagectomy even in patients with localized squamous cell cancer of the
      middle or lower esophagus. In case of high surgical risk chemoradiation should be
      offered to those patients as the therapy of choice. Esophagectomy should be
      performed in operable patients suffering from resectable adenocarcinoma of the
      esophagus. Preoperative chemoradiation is recommended in locally advanced (non
      resectable) adenocarcinoma. If staging reveals distant metastases, palliative
      therapy is indicated. Palliative chemotherapy with 5-fluorouracil and cisplatin
      should be offered to patients with good performance status. Esophageal intubation
      (with expandable metal stents) is the palliative treatment of choice for firm
      stenosing, non-resectable tumors, where rapid relief of dysphagia is required.

PMID- 15248112
TI  - Diagnosis and therapy of intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is characterized by the occurrence of
      pruritus mostly in the third trimenon. Diagnosis is based on the presence of
      pruritus and elevated levels of serum bile acids in the absence of pruritic skin
      diseases. There is strong evidence of a genetic predisposition for ICP. Numerous
      studies have investigated the association of known cholestasis genes such as
      ABCB4 (also designated MDR3), ABCB11 ( BSEP) and ATP8B1 ( FIC1) with ICP. The
      results of these studies implicate a heterogeneous etiology of this syndrome. ICP
      increases the risk of preterm delivery and fetal loss. Furthermore, intense
      pruritus may necessitate premature induction of labor with its known higher
      frequency of complications for mother and child. Therefore, ICP pregnancies
      should be managed as high-risk pregnancies. Pharmaceuticals to alleviate pruritus
      or improve cholestasis like antihistamines, phenobarbital, anion exchange resins,
      dexamethasone or S-adenosylmethionine are not widely accepted because of
      questionable efficacy or side effects. Recent randomized studies have shown
      beneficial effects of ursodeoxycholic acid (UDCA) on laboratory data and pruritus
      in patients with ICP. Improved knowledge about the diagnostic classification of
      different types and pathophysiological mechanisms of ICP may allow for a more
      targeted treatment of this disease in future.

PMID- 15248119
TI  - Pleiotropic effects of the Arabidopsis cryptochrome 2 allelic variation underlie
      fruit trait-related QTL.
AB  - The previous molecular identification of a flowering time QTL segregating in the
      Arabidopsis L er x Cvi cross, demonstrated that natural allelic variation at the
      blue light photoreceptor CRY2 gene affects flowering time (El-Assal et al.,
      2001). In addition, previous works on the same cross have mapped several QTL
      affecting other unrelated life history traits in the CRY2 genomic region. In the
      present report, we have used a set of Arabidopsis L er transgenic plants carrying
      four different functional CRY2 transgenes for phenotypic analyses, with the aim
      of exploring the extent of pleiotropy of CRY2 allelic variation. It is concluded
      that previously identified QTL affecting fruit length, ovule number per fruit,
      and percentage of unfertilized ovules are caused by this same Ler/Cvi CRY2
      allelic variation. In addition, dose effects of the CRY2-L er allele are detected
      for fruit length. A seed weight QTL at the map position of CRY2 could not be
      confirmed and also no effect on seed dormancy was observed. Thus, it is shown
      that transgenic plants carrying different alleles can be a useful tool to
      attribute QTL for different complex traits to a specific locus, even when the
      relationship among the traits has not been previously suggested.

PMID- 15248120
TI  - Seed development and differentiation: a role for metabolic regulation.
AB  - During seed growth, the filial organs, Vicia embryos and barley endosperm,
      differentiate into highly specialized storage tissues. Differentiation is evident
      on structural and morphological levels and is reflected by the spatial
      distribution of metabolites. In Vicia embryos, glucose is spatially correlated to
      mitotic activity whereas elongating and starch accumulating cells contain high
      levels of sucrose. Seed development is also regulated by phytohormones. In pea
      seeds, GA-deficiency stops seed growth before maturation. In Arabidopsis seeds,
      ABA regulates differentiation and inhibits cell division activity. The ABA
      pathway, in turn, is linked to sugar responses. In young Vicia embryos,
      invertases in maternal tissues control both concentration and composition of
      sugars. Embryonic and endospermal transfer cell formation represents an early
      differentiation step. Establishing an epidermis-localised sucrose uptake system
      renders the embryo independent from maternal control. cDNA array analysis in
      barley seeds revealed a massive transcriptional re-programming of gene expression
      during the transition stage, when gene clusters related to transport and energy
      metabolism are highly transcribed. Sucrose represents a signal for
      differentiation and up-regulates storage-associated gene expression. Sucrose
      signalling involves protein phosphorylation. Sucrose non-fermenting-1-related
      protein kinases are apparently induced in response to high cellular sucrose, and
      could act as mediators of sucrose-specific signals. Energy metabolism changes
      during seed development. In Vicia embryos metabolic responses upon hypoxia and
      low energy charge levels are characteristic for young undifferentiated stages
      when energy demand and respiration are high. During the transition stage, the
      embryo becomes adapted to low energy availability and metabolism becomes
      energetically more economic and tightly controlled. These adaptations are
      embedded in the embryo's differentiation program and coupled with
      photoheterotrophic metabolism. In Vicia cotyledons, ATP content increases in a
      development-dependent pattern and is associated with the greening process. The
      main role of seed photosynthesis is to increase internal O2 contents and to
      control biosynthetic fluxes by improving energy supply.

PMID- 15248121
TI  - Indirect defence of plants against herbivores: using Arabidopsis thaliana as a
      model plant.
AB  - In their defence against pathogens, herbivorous insects, and mites, plants employ
      many induced responses. One of these responses is the induced emission of
      volatiles upon herbivory. These volatiles can guide predators or parasitoids to
      their herbivorous prey, and thus benefit both plant and carnivore. This use of
      carnivores by plants is termed indirect defence and has been reported for many
      plant species, including elm, pine, maize, Lima bean, cotton, cucumber, tobacco,
      tomato, cabbage, and Arabidopsis thaliana. Herbivory activates an intricate
      signalling web and finally results in defence responses such as increased
      production of volatiles. Although several components of this signalling web are
      known (for example the plant hormones jasmonic acid, salicylic acid, and
      ethylene), our understanding of how these components interact and how other
      components are involved is still limited. Here we review the knowledge on
      elicitation and signal transduction of herbivory-induced volatile production.
      Additionally, we discuss how use of the model plant Arabidopsis thaliana can
      enhance our understanding of signal transduction in indirect defence and how
      cross-talk and trade-offs with signal transduction in direct defence against
      herbivores and pathogens influences plant responses.

PMID- 15248122
TI  - The cell wall-modifying xyloglucan endotransglycosylase/hydrolase LeXTH1 is
      expressed during the defence reaction of tomato against the plant parasite
      Cuscuta reflexa.
AB  - A suppressive subtractive hybridization technique was used to identify genes,
      which were induced during the early phases of the interaction between dodder
      (Cuscuta reflexa), a phanerogamic parasite, and its incompatible host plant
      tomato. One of the identified genes encodes a tomato xyloglucan
      endotransglycosylase/hydrolase (XTH)--an enzyme involved in cell wall elongation
      and restructuring. The corresponding LeXTH1 mRNA accumulated 6 h after attachment
      of the parasite. In contrast, wounding did not influence the expression level.
      Subsequent to LeXTH1 mRNA accumulation, an increase in XTH activity at the
      infection sites as well as in adjacent tissues was observed. The effect of IAA on
      LeXTH1 expression was analyzed because the concentration of this phytohormone is
      known to increase in the tomato tissue during the interaction with the parasite.
      LeXTH1 mRNA accumulation was in fact induced by external application of auxin.
      However, in the auxin-insensitive tomato mutant diageotropica, Cuscuta induced
      LeXTH1-mRNA accumulated with a time course similar to wild type tomato. Thus,
      auxin appears not to be an essential signal for infection-induced LeXTH1
      activation. Our data suggest a role for xyloglucan transglycosylation in defence
      reactions associated with the incompatible tomato- Cuscuta interaction.

PMID- 15248123
TI  - Coordinated expression of sulfate uptake and components of the sulfate
      assimilatory pathway in maize.
AB  - A high-affinity-type sulfate transporter (Group 1: ZmST1;1, Accession No.
      AF355602) has been cloned from maize seedlings by RT-PCR. Tissue and cell
      specific localisation of this sulfate transporter has been determined along the
      developmental gradient of the root and in leaves of different ages. In S
      sufficient conditions there was uniform low expression of ZmST1;1 in the root and
      very low expression in the leaves. Increased mRNA abundance and sulfate influx
      capacity indicated that S-starvation increased ZmST1;1 expression in roots,
      especially at the top of the root (just behind the seed, the area possessing most
      laterals and root hairs) compared to the root tip. Similarly a group 2, probable
      low affinity-type sulfate transporter, ZmST2;1, and also ATP-sulfurylase and APS
      reductase but not OAS(thiol)lyase were induced by S-starvation and showed highest
      expression in the upper section of the root. S-starvation increased root/shoot
      ratio by 20 % and increased root lateral length and abundance in the region
      closest to the root tip. As the increase in root proliferation was not as great
      as the increase in mRNA pools, it was clear that there was a higher cellular
      abundance of the mRNAs for sulfate transporters, ATP-sulfurylase, and APS
      reductase in response to sulfur starvation. In the leaves, the sulfate
      transporters, ATP-sulfurylase and APS-reductase were induced by S-starvation with
      the most mature leaf showing increased mRNA abundance first. In situ
      hybridization indicated that ZmST1;1 was expressed in epidermal and endodermal
      cell layers throughout the root whilst OAS(thiol)lyase was highly expressed in
      the root cortex.

PMID- 15248124
TI  - Aquaporin functionality in roots of Zea mays in relation to the interactive
      effects of boron and salinity.
AB  - Zea mays L. cv. amylacea, a plant tolerant of B and salinity, was used to
      determine the involvement of aquaporin functionality in the interactive effects
      of B and salinity. Also, growth, chlorophyll concentration, and water relations
      were studied. While growth and chlorophyll concentration did not show noticeable
      changes under saline conditions, the decrease in leaf water potential and osmotic
      potential, together with the marked decrease of stomatal conductance and root
      hydraulic conductance, showed that the plants were adjusted osmotically. However,
      no effect of B was observed. The very weak response of the Lpc of salt-stressed
      roots to Hg suggested that water channels were greatly reduced in number or, if
      present, were non-functional. The evidence that substantial B movement can occur
      through diffusion and channel-mediated transport is compelling, and could account
      for B uptake under conditions of adequate or greater B supply. Therefore, the
      reduction in the functionality of aquaporins for NaCl-treated plants could be
      related to the reduction of B concentrations in roots and leaves in B + NaCl
      treated plants, in comparison with plants treated only with B.

PMID- 15248125
TI  - Tyrosine phosphorylation inhibits the interaction of 14-3-3 proteins with the
      plant plasma membrane H+-ATPase.
AB  - Interaction of 14-3-3 proteins with their targets depends not only on the
      phosphorylation status of the target but also on that of 14-3-3 (Fu et al.,
      2000). In this work we demonstrated that the maize 14-3-3 isoform GF14-6 is a
      substrate of the tyrosine kinase insulin growth factor receptor 1. By means of
      site-directed mutants of GF14-6, we identified Tyr-137 as the specific tyrosine
      residue phosphorylated by the insulin growth factor receptor 1. Phosphorylation
      of GF14-6 on Tyr-137 lowered its affinity for a peptide mimicking the 14-3-3
      binding site of the plant plasma membrane H+-ATPase. Moreover, phosphorylation in
      planta of 14-3-3 tyrosine residues, resulting from incubation with the tyrosine
      phosphatase inhibitor, phenylarsine oxide, decreased their association to the H+
      ATPase.

PMID- 15248126
TI  - Two-dimensional tension tests in plant biomechanics--sweet cherry fruit skin as a
      model system.
AB  - Splitting of fruits is a function of two-dimensional tension caused by different
      growth rates of tissues and turgor, especially water uptake shortly before
      harvest. In order to analyse the mechanical properties of spheroid plant material
      close to stress-strain conditions in vivo, a new hydraulic two-dimensional
      testing device was set up. Sweet cherry (Prunus avium L.) fruit skin was chosen
      as a model system. The recorded pressure-deflection curves were non-linear, with
      a considerable initial "lag phase" and a distinct increasing end part. Taking
      into account the special geometry, these curves could be modelled with a newly
      developed analytical approach based on linear elastic material behaviour. The
      results demonstrated good correlation if a modulus of elasticity ranging from 160
      to 250 MPa for the cherry fruit skin was chosen. In addition, a mean strength
      value of 47 MPa was calculated based on the theory of thin shells and spheres.
      The results are compared with mechanical data found for fruits and other plant
      material. In order to test the theoretical approach, two- and one-dimensional
      tension tests were performed on packaging PE foil, revealing a mean modulus of
      171 MPa in bi-axial tension, and 193 and 242 MPa in uni-axial tension, depending
      on the test speed. The results demonstrate that it seems to be feasible to use
      this method to analyse the two-dimensional stress-strain conditions of spheroid
      plant materials such as cherry fruit skins. It may be applied as a tool for crop
      testing to elucidate the mechanical basis of cracking susceptibility of fruits.

PMID- 15248127
TI  - QTL mapping for a trade-off between leaf and bud production in a recombinant
      inbred population of Microseris douglasii and M. bigelovii (Asteraceae,
      Lactuceae): a potential preadaptation for the colonization of serpentine soils.
AB  - The different response to growth on serpentine soil is a major autecological
      difference between the annual asteracean species Microseris douglasii and M.
      bigelovii, with nearly non-overlapping distribution ranges in California. Early
      flowering and seed set is regarded as a crucial character contributing to escape
      drought and thus is strongly correlated with survival and reproductive success on
      serpentine as naturally toxic soil. M. bigelovii (strain C94) from non-serpentine
      soil produces more leaves at the expense of bud production in the first growing
      phase than M. douglasii (B14) from serpentine soil. A QTL mapping study for this
      trade-off and for other growth-related traits was performed after six generations
      of inbreeding (F7) from a single interspecific hybrid between B14 and C94 on
      plants that were grown on serpentine and alternatively on normal potting soil.
      The trade-off is mainly correlated with markers on one map region on linkage
      group 03a (lg03a) with major phenotypic effects (phenotypic variance explained
      [PVE] = 18.8 - 31.7 %). Plants with the M. douglasii allele in QTL-B1 (QTL-NL1)
      produce more buds but fewer leaves in the first 119 days on both soil types.
      Three modifier QTL could be mapped for bud and leaf production. In one modifier
      (QTL-B2 = QTL-NL4) the M. douglasii allele is again associated with more buds but
      fewer leaves. QTL mapped for bud set in the F6 co-localize with QTL-B1 (major
      QTL) and QTL-B3. Two additional QTL for leaf length and red coloration of leaves
      could be mapped to one map region on lg03a. Co-localization of the two QTL loci
      with major phenotypic effects on bud and leaf production strongly suggests that a
      major genetic locus controls the trade-off between the two adaptive traits. The
      importance of mutational changes in major genes for the adaptation to stressful
      environments is discussed.

PMID- 15248128
TI  - Phylogenetic position of endosymbiotic green algae in Paramecium bursaria
      Ehrenberg from Japan.
AB  - Endosymbiotic green algae of Japanese Paramecium bursaria were phylogenetically
      analyzed based on DNA sequences from the ribosomal DNA operon (18S rDNA, ITS1,
      5.8S rDNA, and ITS2). Phylogenetic trees constructed using 18S rDNA sequences
      showed that the symbionts belong to the Chlorella sensu stricto
      (Trebouxiophyceae) group. They are genetically closer to the C. vulgaris
      Beijerinck group than to C. kessleri Fott et Novakova as proposed previously.
      Branching order in C. vulgaris group was unresolved in 18S rDNA trees. Compared
      heterogeneities of 18S rDNA, ITS1, 5.8S r, and ITS2 among symbionts and two
      Chlorella species, indicated that the ITS2 region (and probably also ITS1) is
      better able to resolve phylogenetic problems in such closely related taxa. All
      six symbiotic sequences obtained here (approximately 4000-bp sequences of 18S
      rDNA, ITS1, 5.8S rDNA, and ITS2) were completely identical in each, strongly
      suggesting a common origin.

PMID- 15248129
TI  - Molecular phylogeny of Anthyllis spp.
AB  - For the genus Anthyllis (Fam. Fabaceae, tribe Loteae), with few exceptions,
      little information is available on the genetic variation among and within
      species. This genus contains 20 species distributed throughout Europe, Africa,
      and the Mediterranean basin. The most widespread species is A. vulneraria, and
      over 30 intraspecies taxa have been identified based on plant morphology. To
      study the molecular phylogeny of the genus, the sequences of the internal
      transcribed spacers ITS1 and ITS2 of the nuclear ribosomal DNA of 10 Anthyllis
      species, including 11 subspecies of A. vulneraria and three subspecies of A.
      montana, were obtained and analysed together with sequences of five other species
      of the genus obtained from GenBank. Our results suggest that the genus Anthyllis
      is not monophyletic and is divided in two main clades: the Anthyllis sensu
      strictu and the "tetraphylla clade". The former includes most of the Anthyllis
      species, and the latter includes three annual species more closely related to
      Lotus. All the taxa were also analysed according to seven chloroplast
      microsatellites, and these data closely confirm the results obtained with the ITS
      phylogeny.

PMID- 15248130
TI  - Succession in inland sand ecosystems: which factors determine the occurrence of
      the tall grass species Calamagrostis epigejos (L.) Roth and Stipa capillata L.?
AB  - In many successional series, grass species play an important role in mid
      successional stages. Using calcareous sand ecosystems in the northern upper Rhine
      valley (Germany) as a model, we analyzed successional trajectories and the
      factors that determine their direction. A 5- to 7-year study of 23 permanent
      plots is presented. Polar ordination revealed that succession starts with pioneer
      communities (dominated by Corynephorus canescens and cryptogams) and can
      eventually lead to relatively stable Calamagrostis epigejos or Stipa capillata
      tall grass stands. At some sites, Cynodon dactylon can play a major role, but we
      focused on the two previously mentioned species. Gradient analyses of their
      ecological amplitudes by means of principal components and regression analysis
      were carried out in order to elucidate the factors determining the successional
      trajectories. Soil analyses of 71 plots established significantly positive linear
      relations for C. epigejos with respect to total nitrogen, extractable phosphate
      and potassium, as well as soil moisture indicator values. C. epigejos is not able
      to spread if the stress factors nutrient deficiency and dryness are combined.
      Lower tolerance limits are presented. In contrast, S. capillata shows negative
      relations to phosphate, declining strongly at P contents > 20 mg kg(-1). At a
      moisture indicator value of around 3.2 (indicating dry sites), S. capillata
      reaches its optimum. S. capillata is a model for a tall grass species which, even
      with low nutrient levels and dry soil conditions, can be successful in mid
      successional phases; but it is displaced by C. epigejos if soil moisture
      increases or phosphate/potassium supply is higher. Regarding a general framework,
      the successional phases are characterized by processes such as replacement of
      species, facilitation, and inhibition.

PMID- 15248131
TI  - Evolution of carnivory in Lentibulariaceae and the Lamiales.
AB  - As a basis for analysing the evolution of the carnivorous syndrome in
      Lentibulariaceae (Lamiales), phylogenetic reconstructions were conducted based on
      coding and non-coding chloroplast DNA (matK gene and flanking trnK intron
      sequences, totalling about 2.4 kb). A dense taxon sampling including all other
      major lineages of Lamiales was needed since the closest relatives of
      Lentibulariaceae and the position of "proto-carnivores" were unknown. Tree
      inference using maximum parsimony, maximum likelihood, and Bayesian approaches
      resulted in fully congruent topologies within Lentibulariaceae, whereas
      relationships among the different lineages of Lamiales were only congruent
      between likelihood and Bayesian optimizations. Lentibulariaceae and their three
      genera (Pinguicula, Genlisea, and Utricularia) are monophyletic, with Pinguicula
      being sister to a Genlisea-Utricularia clade. Likelihood and Bayesian trees
      converge on Bignoniaceae as sister to Lentibulariaceae, albeit lacking good
      support. The "proto-carnivores" (Byblidaceae, Martyniaceae) are found in
      different positions among other Lamiales but not as sister to the carnivorous
      Lentibulariaceae, which is also supported by Khishino-Hasegawa tests. This
      implies that carnivory and its preliminary stages ("proto-carnivores")
      independently evolved more than once among Lamiales. Ancestral states of
      structural characters connected to the carnivorous syndrome are reconstructed
      using the molecular tree, and a hypothesis on the evolutionary pathway of the
      carnivorous syndrome in Lentibulariaceae is presented. Extreme DNA mutational
      rates found in Utricularia and Genlisea are shown to correspond to their unusual
      nutritional specialization, thereby hinting at a marked degree of carnivory in
      these two genera.

PMID- 15248132
TI  - Phenology, sex ratio, and spatial distribution among dioecious species of
      Trichilia (Meliaceae).
AB  - The flowering, sex ratio, and spatial distribution of four dioecious species of
      Trichilia (Meliaceae) were studied in a semi-deciduous forest in southeastern
      Brazil. All reproductive trees (T. clausseni, T. pallida and T. catigua) with dbh
      > or = 5 cm within a 1-ha plot were collected, sexed, mapped and, for individuals
      of each species, the distances to the nearest neighbour of the same and opposite
      sex were measured. For the shrub species T. elegans (dbh < 5 cm), all
      reproductive individuals were sampled randomly in 10 samples of 10 x 10 m. The
      reproductive phenology was observed at weekly to monthly intervals from May 1988
      to January 1990. The species are strictly dioecious, did not present any sex
      mixed trees or sex switching during the study, and sex ratio did not differ
      significantly from 1 : 1. The size distributions and the relative size variation
      were not significantly different between sexes. There was no significant
      segregation or clumping between individuals of either sex and no fruit production
      without pollination. Onset of flowering and flowering peak were synchronous
      between male and female plants for all species studied. Flower synchrony was
      related to outcrossing and pollinator attraction rather than climatic factors.

PMID- 15248133
TI  - The distribution and phylogeny of aluminium accumulating plants in the Ericales.
AB  - The distribution of aluminium (Al) accumulation in the Ericales is surveyed,
      based on semi-quantitative tests of 114 species and literature data. Al
      accumulation mainly characterises the families Diapensiaceae, Pentaphylacaceae,
      Symplocaceae, Ternstroemiaceae, and Theaceae. Al accumulation is consistently
      present or absent in most families examined, but the character appears to be more
      variable in a few taxa (e.g., Lecythidaceae, Myrsinaceae). Although the
      interfamilial relationships within the Ericales require further research, the
      ability to accumulate high levels of Al appears to show considerable taxonomic
      significance. While the majority of Al accumulating Ericales includes woody,
      tropical plants, the feature is remarkably present in several herbaceous
      Diapensiaceae, which have a distribution in cold to temperate areas. The
      association of different mycorrhizae types with plant roots is suggested to play
      a role in the exclusion of high Al levels from the shoot.

PMID- 15248134
TI  - Non-Euglossine bees also function as pollinators of Sinningia species
      (Gesneriaceae) in southeastern brazil.
AB  - Pollination by male and female Euglossini bees, euglossophily, was suggested for
      a number of neotropical Gesneriaceae species. Information on bee species other
      than Euglossini as pollinators of neotropical members of this family is limited,
      and in the tribe Sinningieae data about bee pollination are still lacking. Here,
      we report on floral biology and bee pollination of four Sinningia species: S.
      schiffneri, S. eumorpha, S. villosa, and Sinningia "canastrensis". The flower
      features, such as corolla size, shape, and colour, are very different among the
      four species, but all conform to the melittophilous syndrome. The average nectar
      volume and sugar amount is low in S. schiffneri, S. eumorpha, and Sinningia
      "canastrensis", when compared to that of S. villosa, but low nectar amounts is a
      general feature of Sinningia species. The main pollinators of the four species
      are: small Tapinotaspidini (Trigonopedia ferruginea) of S. schiffneri, large
      Bombini (Bombus morio) and large Centridini (Epicharis morio) of S. eumorpha,
      large Euglossini (Eulaema cingulata and Eufriesea surinamensis) of S. villosa,
      and large Euglossini (Eufriesea violascens) and Megachilini (Megachile sp.) of
      Sinningia "canastrensis". Out of the four species, only S. villosa is exclusively
      Euglossini-pollinated. The marked differences in flower features and nectar
      production of these Sinningia species may reflect their pollination by distinct
      groups of bees. These results strengthen the idea of multiple origins for the
      pollination systems involving bees within this genus, which is highly supported
      by molecular phylogenetic analyses.

PMID- 15248135
TI  - Determinants of sustained virological suppression in indigent, HIV-infected
      patients: is single protease inhibitor-based antiretroviral therapy truly highly
      active?
AB  - BACKGROUND: Effective virological suppression with HAART is dependent on strict
      adherence to therapy. Compliance with therapy is influenced by clinical and
      psychosocial factors. METHOD: We performed a retrospective study investigating
      determinants of effective virological suppression, defined as <400 RNA at 11-13
      months of HAART, in an urban indigent population. The study included 366 new
      patients presenting for care to the Thomas Street Clinic, Houston, Texas, between
      April and December 1998. Median age, CD4 count, and viral load (VL) of the study
      population were 37.5 years, 189 cells/mm(3), and 53,000, respectively. Thirty
      nine percent had AIDS, 20% had cocaine-positive drug screens, and 64% were
      antiretroviral naive. Two hundred and sixty-seven patients were started on HAART.
      Thirty-four percent showed virological suppression. RESULTS: In multivariate
      analysis, adherence to HAART, care by experienced primary provider, baseline VL
      <100,000 copies/mL, age >35 years, and no active substance use were associated
      with virological suppression. Rates of virological suppression with HAART are
      unacceptably low in this urban indigent population. CONCLUSION: Low rates of
      virological suppression are primarily due to lack of adherence rather than late
      utilization of care among ethnic minorities. Single protease-inhibitor-based
      antiretroviral therapy does not appear to be highly active in this patient
      population.

PMID- 15248136
TI  - Impact of chronic hepatitis C on HIV-1 disease progression.
AB  - BACKGROUND: Although there is clear evidence of an accelerated progression of
      liver fibrosis in HIV-positive patients with chronic hepatitis C virus (HCV)
      infection, it is unclear whether HCV infection may influence HIV-1 disease
      progression. We have analyzed the impact of HCV on CD4 counts and plasma HIV RNA
      in a large group of HIV-positive individuals. METHOD: Epidemiological data, CD4
      counts, and plasma HIV RNA values were recorded from 902 consecutive HIV-1
      positive persons who attended our institution since 1998. RESULTS: HCV infection
      was documented (antibodies and/or HCV RNA) in 72% of the total study population.
      The higher rates were seen among intravenous drug users (97%) compared to other
      groups (17% in homosexual men, 23% in patients who acquired HIV heterosexually).
      In a cross-sectional analysis performed at the first trimester of 2000, the mean
      CD4 count was lower among HCV-positive than among HCV-negative individuals (518
      +/- 282 cells/microL vs. 620 +/- 302 cells/microL; p <.001). The mean plasma HIV
      RNA was 11,188 +/- 55,301 copies/mL in HCV-positive persons versus 6,352 +/-
      32,152 copies/mL in HCV-negative persons (p =.03). Undetectable plasma HIV RNA
      (<50 copies/mL) was recognized in 54% of HCV-positive persons versus 64% of HCV
      negative persons (p =.04); a similar proportion of patients in each group was on
      antiretroviral therapy (90% vs. 93%) or HAART (86% vs. 89%). When comparing data
      from 1998 and 2000, the CD4 count increased an average of 53 cells/microL (11%)
      in HCV-positive persons versus 111 (19%) in HIV-negative persons during this 2
      year interval (p <.05). Plasma HIV RNA on average declined 606 copies/mL (5%) in
      HCV-positive persons versus 5,788 copies/mL (54%) in HCV-negative persons (p
      <.05). A significant association between HCV infection and CD4 counts was
      recognized in the multivariate analysis, which was independent of gender, age,
      plasma HIV RNA, use of HAART, and adherence to therapy. In contrast, no
      significant effect of HCV on HIV RNA was found. CONCLUSION: Hepatitis C may be
      associated with a poor immunologic outcome in HIV-infected persons. This worst
      influence is not explained by a lower rate of antiretroviral therapy among HCV
      positive persons nor a much poorer drug adherence in this population. Therefore,
      hepatitis C may act as a direct cofactor for HIV disease progression. If so,
      treatment of chronic hepatitis C might indirectly benefit HIV disease.

PMID- 15248137
TI  - Health-related quality of life in HIV-infected naive patients treated with
      nelfinavir or nevirapine associated with ZDV/3TC (the COMBINE-QoL substudy).
AB  - PURPOSE: The aim of the study was to assess differences in health-related quality
      of life (HRQoL) in HIV-infected naive patients treated with two HAART regimens at
      12 months. METHOD: The MOS-HIV questionnaire was used to measure HRQoL in a
      subgroup of 127 patients included in the COMBINE study, which was an open-label,
      randomized, multicenter study comparing zidovudine (ZDV) and lamivudine (3TC)
      plus nelfinavir (NFV) or nevirapine (NVP) regimens in HIV-infected naive
      patients. 63 patients were included in the ZDV/3TC/NFV arm and 64 in the
      ZDV/3TC/NVP arm. RESULTS: No statistically significant differences were observed
      at baseline in demographic and clinical variables and HRQoL scores between
      treatment groups, except that the proportion of homosexual men was higher in the
      ZDV/3TC/NVP arm. There were no statistically significant differences in HRQoL
      scores between arms at 12 months and over time; only ZDV/3TC/NVP patients showed
      statistically significant improvement in Physical Health Summary score (p <.01)
      and a trend toward a better profile in Mental Health Summary score (p =.07).
      Overall, patients who were treated with ZDV/3TC/NVP showed greater changes in
      physical dimensions and patients who were treated with ZDV/3TC/NFV showed greater
      changes in mental health. CONCLUSION: Differences in HRQoL between study groups
      at 1 year follow-up were not detected. Nevertheless, a trend toward improvement
      was observed in summary health scores in ZDV/3TC/NVP-treated patients.

PMID- 15248138
TI  - Clinical characteristics of gastrointestinal lymphomas associated with AIDS (GI
      ARL) and the impact of HAART.
AB  - PURPOSE: The gastrointestinal (GI) tract is the most common site of extranodal
      disease in patients with systemic non-Hodgkin's lymphoma (NHL). Patients with
      systemic NHL and GI involvement associated with AIDS (GI-ARL) have a
      significantly worse prognosis than those without AIDS. We studied whether the
      introduction of HAART is associated with improved survival in patients with GI
      ARL. PATIENTS AND METHOD: 36 patients with GI-ARL were identified from the tumor
      registries of a large municipal hospital in New York City and a tertiary care
      facility in western New York State. Of these, 28 patients did not receive HAART
      and 8 were treated with HAART. The primary endpoint was survival, which was
      defined as time from date of diagnosis of NHL until death from any cause.
      RESULTS: Patients were analyzed based on whether or not they were treated with
      HAART. Kaplan-Meier analysis showed significantly better survival in patients
      with GI-ARL who were concurrently treated with HAART (p =.014). Median survival
      was 5 months for the no-HAART group and 30 months for the HAART group.
      CONCLUSION: In patients with GI-ARL who were treated with chemotherapy,
      concurrent therapy with HAART therapy was associated with improved survival.

PMID- 15248139
TI  - Nitric oxide production in HIV-1 infected patients receiving intermittent cycles
      of interleukin-2 and antiretrovirals.
AB  - BACKGROUND: Interleukin-2 (IL-2) has been investigated as an adjunct to
      antiretroviral therapy (ART) because of its well-demonstrated capacity of stably
      increasing the number of peripheral CD4+ T cell lymphocytes. However, IL-2
      related adverse events (AEs), including fever, tachycardia, hypotension, and
      respiratory failure, are typically dose- and schedule-dependent and can
      potentially limit the application of IL-2 therapy in an outpatient setting.
      Nitric oxide (NO) is a potent vasodilator potentially responsible for some of the
      AEs caused by IL-2. PURPOSE: In this study, we determined NO production in a
      cohort of HIV-1 infected individuals receiving ART either alone or together with
      IL-2. METHOD: NO production, detected as plasma nitrate/nitrite levels by the
      Griess reaction, was evaluated in 3 groups of 10 individuals each. In the first
      group, subcutaneous (sc) administration of 12-15 million international units per
      day (MIU/d) of IL-2 was administered for 5 days every 8 weeks for 6 cycles
      together with ART; in the second group, IL-2 (6 MIU/d) was given sc for 5 days
      every 4 weeks for 12 cycles together with ART; whereas the third group received
      ART alone. RESULTS: At baseline, the plasma nitrate/nitrite levels in the 2
      groups of patients who received high and low doses of the cytokine along with ART
      were 28.5 +/- 18.1 micromol/L and 34.2 +/- 29.0 micromol/L, respectively. These
      levels were comparable to those of patients treated with only ART (18.6 +/- 22.4
      micromol/L) and to those of 20 healthy controls (19.9 +/- 5.9 micromol/L). No
      significant increase of plasma nitrate/nitrite levels was observed by
      administration of either ART or ART+IL-2. In addition, NO production was not
      associated significantly with different levels of tumor necrosis factor-alpha, IL
      6, or soluble IL-2 receptor alpha chain in 9 individuals with WHO grade 2 and 3
      AEs. CONCLUSION: Our results indicate that NO is unlikely to be responsible for
      most side effects of IL-2 therapy in HIV-1 infected individuals. Because both IL
      2 and virus multiplication have been reported to independently stimulate NO
      production, concomitant ART may curtail NO production through inhibition of HIV-1
      replication.

PMID- 15248140
TI  - Update on HIV lipodystrophy.
AB  - When prescribed appropriately and taken adherently, antiretroviral therapy can
      consistently and durably suppress HIV replication, potentially translating into
      years of near normal health for HIV-infected persons. However, presently
      available antiretrovirals are associated with a cluster of physical and metabolic
      symptoms termed HIV lipodystrophy. This article reviews the state of knowledge
      about the pathogenesis and treatment of the various manifestations of these
      adverse effects.

PMID- 15248141
TI  - DHHS issues adult guideline revisions.

PMID- 15248142
TI  - Immune reconstitution and control of HIV.

PMID- 15248143
TI  - Molecular characterization and transcriptional regulation of nitrate reductase in
      a ruminal bacterium, Selenomonas ruminantium.
AB  - Nitrate reductase (NaR) of a strain of Selenomonas ruminantium was purified, and
      the gene encoding NaR (nar) was sequenced. The 6.4 kbp nar gene consisted of
      narG, H, J, and I in this order. The deduced amino acid sequences of these
      subunits resembled those of membrane-bound nitrate reductase-A reported for
      Escherichia coli. It was shown that narG, H, J, and I are transcribed as a single
      polycistronic message (nar operon). The level of intracellular nar-mRNA was
      higher when S. ruminantium was grown with nitrate than when grown without
      nitrate, suggesting that nar transcription is enhanced by nitrate. The level of
      nar-mRNA, which was in parallel to the amount of NaR per cellular nitrogen, was
      suggested to be enhanced in response to the deficiency of energy and electron
      supply. Therefore, NaR synthesis in S. ruminantium appeared to be regulated at
      the transcriptional level in response to the availability of energy and
      electrons. S. ruminantium reduced nitrate and fumarate simultaneously with no
      significant effect of fumarate on nar transcription. Addition of fumarate
      stimulated nitrate reduction, which was caused by increased cell growth because
      of increased acquirement of ATP via electron transport phosphorylation coupled
      with fumarate reduction.

PMID- 15248144
TI  - Cryptococcus paraflavus sp. nov. (Tremellales), isolated from steppe plants in
      Russia.
AB  - Three strains related to Cryptococcus flavus were isolated from plants collected
      in the Prioksko-terrasny biosphere reserve (Russia). Physiological
      characterization, mycocinotyping, sequencing of the D1/D2 domain of the 26S rDNA
      and the ITS region revealed their separate taxonomic position. The name
      Cryptococcus paraflavus is proposed to accommodate these isolates (type strain
      VKM Y-2923).

PMID- 15248145
TI  - Effects of the overexpression of fructose-1,6-bisphosphate aldolase on
      fermentation pattern and transcription of the genes encoding lactate
      dehydrogenase and pyruvate formate-lyase in a ruminal bacterium, Streptococcus
      bovis.
AB  - Whether fructose-1,6-bisphosphate (FBP) triggers the transcriptional regulation
      of the gene expression of lactate dehydrogenase (LDH) and pyruvate formate-lyase
      (PFL) in Streptococcus bovis was examined by constructing a recombinant strain
      that overexpresses FBP aldolase (FBA). When the recombinant strain was grown on
      glucose, intracellular FBP was much lower as compared to the parent strain,
      whereas dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde-3-phosphate (GAP)
      were slightly higher. Intracellular ATP and ADP were slightly lower, but the
      NADH/NAD(+) ratio was not different. When glucose was replaced by lactose, a less
      readily utilized substrate, there was no great difference in FBP, DHAP, GAP, or
      adenine nucleotides. Overexpression of FBA decreased the level of LDH-mRNA, and
      increased the level of PFL-mRNA. Consequently, FBP concentration was positively
      related to the LDH-mRNA level and inversely related to the PFL-mRNA level. On the
      contrary, DHAP and GAP concentrations were positively related to the PFL-mRNA
      level and inversely related to the LDH-mRNA level. The levels of these mRNA were
      proportional to the amounts of corresponding enzymes in cells. As a result, the
      ratio of formate to lactate produced was increased by the overexpression of FBA.
      From these results, it could be presumed that FBP is involved in the
      transcriptional control of LDH and PFL synthesis in S. bovis.

PMID- 15248147
TI  - Development of ecotoxicity assay based on inhibition of respiring activity in
      microbial community using XTT reduction.
AB  - The aim of this study is to develop ecotoxicity assay for evaluating the
      influence of chemicals on a microbial ecosystem based on XTT reduction inhibition
      (XTT assay). XTT reduction method is used for quantification of the microbial
      respiratory activity. Since the XTT assay indicates the inhibition of microbial
      respiratory activity, it could evaluate the toxicity of chemicals. Suitable
      conditions for the XTT assay were determined to be 200 mg/L of particulate
      organic carbon as test microbe concentration and 15 min of assay time using
      activated sludge. Toxicities of several chemicals evaluated by activated sludge
      as test microbes were examined under these conditions. Sensitivity for the
      toxicity evaluated by the XTT assay using activated sludge microbes was almost
      the same value was that for the OECD activated sludge respiration inhibition test
      (ASRI test). XTT assay was also applied for evaluating the influence of chemicals
      on the soil microbial community and the XTT assay was used to evaluate a median
      effective concentration (EC(50)) value of 3,5-dichlorophenol (3,5-DCP). The
      EC(50) value of 3,5-DCP was almost the same as the value using activated sludge
      as test microbes. These results suggest that the XTT assay using both mixed
      cultures of non-contaminated environments and chemical extracts from various
      contaminated environments could evaluate the influence on microbial ecosystems
      affected by toxic chemicals.

PMID- 15248146
TI  - Isolation and characterization of lactobacilli from some traditional fermented
      foods and evaluation of the bacteriocins.
AB  - Lactic acid bacteria (LAB) commonly used in food as starter cultures are known to
      produce antimicrobial substances such as bacteriocins and have great potential as
      food biopreservatives. LAB isolated from traditional fermented foods (appam
      batter and pickles) were screened for bacteriocin production. Two lactobacilli,
      LABB and LABP (one from each source) producing bacteriocins were characterized.
      Both the bacilli were homo-fermentative, catalase negative and micro-aerophilic
      in nature. LABB was found to be a thermobacterium growing at 45 degrees C while
      LABP was a streptobacterium growing at 15 degrees C. Both were able to grow at pH
      4.5-8.6 but were intolerant to high salt concentration. They failed to produce
      gas from glucose as well as ammonia from arginine. Among the sugars examined they
      could not ferment arabinose, raffinose, rhamnose or xylose. Additionally, LABB
      could not ferment esculin, gluconate or mannose. LABB is identified as
      Lactobacillus acidophilus while LABP as Lb. casei. Their bacteriocins showed a
      broad inhibitory spectrum against the indicator organisms tested. They were
      active below pH 8.0 and after autoclaving as well. There was a complete loss of
      activity when treated with proteolytic enzymes such as trypsin indicating the
      proteinaceous nature of the active molecules. SDS-PAGE of partially purified
      bacteriocins indicated the molecular mass of the bacteriocin as 3.8 and 4.5 kDa
      for LABB and LABP respectively.

PMID- 15248148
TI  - dsRNA viruses in Nadsonia fulvescens.

PMID- 15248149
TI  - Novel classes of mutants of the cyanobacterium Nostoc muscorum showing absolute
      requirement of Cs1 or Rb1 for diazotrophy.

PMID- 15248150
TI  - Immobilized lactic acid bacteria for application as dairy starters and probiotic
      preparations.

PMID- 15248151
TI  - Anti-Helicobacter pylori activity of EDTA.

PMID- 15248152
TI  - Paternal germline origin and sex-ratio distortion in transmission of PTPN11
      mutations in Noonan syndrome.
AB  - Germline mutations in PTPN11--the gene encoding the nonreceptor protein tyrosine
      phosphatase SHP-2--represent a major cause of Noonan syndrome (NS), a
      developmental disorder characterized by short stature and facial dysmorphism, as
      well as skeletal, hematologic, and congenital heart defects. Like many autosomal
      dominant disorders, a significant percentage of NS cases appear to arise from de
      novo mutations. Here, we investigated the parental origin of de novo PTPN11
      lesions and explored the effect of paternal age in NS. By analyzing intronic
      portions that flank the exonic PTPN11 lesions in 49 sporadic NS cases, we traced
      the parental origin of mutations in 14 families. Our results showed that all
      mutations were inherited from the father, despite the fact that no substitution
      affected a CpG dinucleotide. We also report that advanced paternal age was
      observed among cohorts of sporadic NS cases with and without PTPN11 mutations and
      that a significant sex-ratio bias favoring transmission to males was present in
      subjects with sporadic NS caused by PTPN11 mutations, as well as in families
      inheriting the disorder.

PMID- 15248154
TI  - Trisomy recurrence: a reconsideration based on North American data.
AB  - Few reliable data exist concerning the recurrence risk for individual trisomies
      or the risk for recurrence of trisomy for a different chromosome. We collected
      records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte
      Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the
      standardized morbidity ratio (SMR), we compared the observed number of trisomies
      at prenatal diagnosis with the expected numbers, given maternal age-specific
      rates (by single year). SMRs were calculated both for recurrence of the same
      trisomy (homotrisomy) and of a different trisomy (heterotrisomy). After all cases
      with an index trisomy 21 were combined, the SMR for homotrisomy was 2.4 (90% CI
      1.6-3.4; P=.0005). For women with both the index trisomy and subsequent prenatal
      diagnosis at age <30 years, the SMR was 8.0; it was 2.1 for women with both
      pregnancies at age >/=30 years. For the other index viable trisomies (13, 18,
      XXX, and XXY) combined, the SMR for homotrisomy was 2.5 (90% CI 0.7-8.0). For
      heterotrisomy, the SMR after an index trisomy 21 was 2.3 (90% CI 1.5-3.8,
      P=.0007); the SMR did not vary with maternal age at the first trisomy. When all
      cases with index viable trisomies were combined, the SMR for heterotrisomy was
      1.6 (90% CI 1.1-2.4; P=.04). For prenatal diagnoses following a nonviable trisomy
      diagnosed in a spontaneous abortion (from Genzyme data only), the SMR for a
      viable trisomy was 1.8 (90% CI 1.1-3.0; P=.04). The significantly increased risk
      for heterotrisomy supports the hypothesis that some women have a risk for
      nondisjunction higher than do others of the same age.

PMID- 15248155
TI  - Industrial microbiology. A new challenge.

PMID- 15248153
TI  - Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2.
AB  - Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and
      complex disease for which only one locus, APOE, has been definitively identified.
      Difficulties in identifying additional loci are likely to stem from inadequate
      linkage analysis methods. Nonparametric methods suffer from low power because of
      limited use of the data, and traditional parametric methods suffer from
      limitations in the complexity of the genetic model that can be feasibly used in
      analysis. Alternative methods that have recently been developed include Bayesian
      Markov chain-Monte Carlo methods. These methods allow multipoint linkage analysis
      under oligogenic trait models in pedigrees of arbitrary size; at the same time,
      they allow for inclusion of covariates in the analysis. We applied this approach
      to an analysis of LOFAD on five chromosomes with previous reports of linkage. We
      identified strong evidence of a second LOFAD gene on chromosome 19p13.2, which is
      distinct from APOE on 19q. We also obtained weak evidence of linkage to
      chromosome 10 at the same location as a previous report of linkage but found no
      evidence for linkage of LOFAD age-at-onset loci to chromosomes 9, 12, or 21.

PMID- 15248156
TI  - Recombinant viruses as tools to induce protective cellular immunity against
      infectious diseases.
AB  - Infections by intracellular pathogens such as viruses, some bacteria and many
      parasites, are cleared in most cases after activation of specific T cellular
      immune responses that recognize foreign antigens and eliminate infected cells.
      Vaccines against those infectious organisms have been traditionally developed by
      administration of whole live attenuated or inactivated microorganisms. Nowadays,
      research is focused on the development of subunit vaccines, containing the most
      immunogenic antigens from the particular pathogen. However, when purified subunit
      vaccines are administered using traditional immunization protocols, the levels of
      cellular immunity induced are mostly low and not capable of eliciting complete
      protection against diseases caused by intracellular microbes. In this review, we
      present a promising alternative to those traditional protocols, which is the use
      of recombinant viruses encoding subunit vaccines as immunization tools.
      Recombinant viruses have several interesting features that make them extremely
      efficient at inducing immune responses mediated by T-lymphocytes. This cellular
      immunity has recently been demonstrated to be of key importance for protection
      against malaria and AIDS, both of which are major targets of the World Health
      Organization for vaccine development. Thus, this review will focus in particular
      on the development of new vaccination protocols against these diseases.

PMID- 15248157
TI  - The Fusarium oxysporum f. sp. ciceris/Cicer arietinum pathosystem: a case study
      of the evolution of plant-pathogenic fungi into races and pathotypes.
AB  - The use of resistant cultivars is one of the most practical and cost-efficient
      strategies for managing plant diseases. However, the efficiency of resistant
      cultivars in disease management is limited by pathogenic variability in pathogen
      populations. Knowledge of the evolutionary history and potential of the pathogen
      population may help to optimize the management of disease-resistance genes,
      irrespective of the breeding strategy used for their development. In this review,
      we examine the diversity in virulence phenotypes of Fusarium oxysporum f. sp.
      ciceris, the causal agent of Fusarium wilt of chickpeas, analyze the genetic
      variability existing within and among those phenotypes, and infer a phylogenetic
      relationship among the eight known pathogenic races of this fungus. The inferred
      intraspecific phylogeny shows that each of those races forms a monophyletic
      lineage. Moreover, virulence of races to resistant chickpea cultivars has been
      acquired in a simple stepwise pattern, with few parallel gains or losses.
      Although chickpea cultivars resistant to Fusarium wilt are available, they have
      not yet been extensively deployed, so that the stepwise acquisition of virulence
      is still clearly evident.

PMID- 15248158
TI  - Dynamics of CaCdc10, a septin of Candida albicans, in living cells and during
      infection.
AB  - The morphogenetic program in the pathogenic fungus Candida albicans, including
      the dimorphic transition, is an interesting field of study, not only because it
      is absent in the commonly used model yeast Saccharomyces cerevisiae, but because
      of the close relationship between hyphal development and virulence of C.
      albicans. We studied one of the most important aspects of fungal morphogenesis-
      the septin ring--in C. albicans. By using a fusion construct to green fluorescent
      protein (GFP), the subcellular localization and dynamics of C. albicans Cdc10 in
      the different morphologies that this fungus is able to adopt was identified. The
      localization features reached were contrasted and compared with the results
      obtained from Candida cells directly extracted from an animal infection model
      under environmental conditions as similar as possible to the physiological
      conditions encountered by C. albicans during host infection.

PMID- 15248159
TI  - G and P genotypes of rotavirus circulating among children with diarrhea in the
      Colombian northern coast.
AB  - A study on the prevalence of rotavirus G and P genotypes was carried out based on
      253 stool specimens obtained from children living in the Colombia northern coast
      region who were less than 3-years-old and who suffered from acute diarrhea. A
      previous study had detected the presence of rotavirus A in 90 (36.5%) of the 246
      samples tested by enzyme immunoassay (EIA), and these strains were investigated
      in the present study. Of these, 50 strains yielded an RNA electropherotype, most
      of which (80.0%) had long profiles and 20.0% of which had short profiles.
      Genotyping of 84 positive samples indicated that 67.9% of the strains could be
      typed. G1 (57.9%), was the most predominant VP7 genotype, followed by G3 (21.1%),
      G9 (15.8%) and G2 (5.3%). Among the VP4 genotypes, P[4] (49.1%) was the most
      prevalent, followed by P[6] 36.4% and P[8] (14.5%). Neither G4 nor G8 nor P[9]
      types were detected. The most common G-P combinations were G3 P[4] (8.8%) and G9
      P[6] (7.0%), followed by G1 P[4] and G1 P[8] (5.3% each). All G1 P[8] strains
      showed long RNA profiles, whereas G3 P[4] and G9 P[6] displayed both long and
      short patterns. Mixed infections involved 21.0% of strains. There was a marked
      diversity among strains collected, and novel strains, including G9, as well as
      other atypical combinations of G and P genotypes, such as G9 P[6] and G3 P[4],
      were found.

PMID- 15248160
TI  - Protein and glycoprotein content of lymphocystis disease virus (LCDV).
AB  - The polypeptide and glycoprotein composition of eight strains of the fish
      pathogenic lymphocystis disease virus (LCDV) isolated from gilt-head seabream
      (Sparus aurata), blackspot seabream (Pagellus bogaraveo), and sole (Solea
      senegalensis) were determined. The protein electrophoretic patterns of all LCDV
      isolates were quite similar regardless of the host fish, showing two major
      proteins (79.9 and 55.6 kDa) and a variable number of minor proteins. Three
      groups of LCDV isolates were distinguished according to the number and molecular
      masses of the minor proteins. Eight glycoproteins were detected inside viral
      particles of LCDV 2, LCDV 3 and LCDV 5 isolates, but only seven glycoproteins
      were found inside viral particles of LCDV 1, LCDV 4, LCDV 6, LCDV 7, and LCDV 11
      isolates and the reference virus ATCC VR 342 by using five lectins. LCDV
      glycoproteins were mainly composed of mannose and sialic acid. These
      glycoproteins could be part of an external viral envelope probably derived from
      the host cell membrane.

PMID- 15248161
TI  - Differential circadian expression of genes fcp2 and fcp6 in Cyclotella cryptica.
AB  - The steady-state mRNA concentrations of two fcp genes encoding fucoxanthin
      chlorophyll a/c light-harvesting polypeptides of the centric diatom Cyclotella
      cryptica were investigated over a 4-day period by RNA dot-blotting experiments.
      Before and during the first day of the experiment, the cultures were grown under
      a 12-h light/12-h dark regime. On the following 3 days, the algae were kept in
      darkness. On the first day, the steady-state mRNA concentration of fcp2 followed
      a diurnal pattern, with a maximum occurring around noon, approximately 6 h after
      the onset of light. The gene fcp6 also had a diurnal pattern on the first day.
      Its maximum, however, occurred immediately after the onset of light. During the
      subsequent incubation period in darkness, the diurnal pattern of expression of
      both fcp genes continued, thus demonstrating that their steady-state mRNA
      concentrations oscillated in a circadian manner.

PMID- 15248162
TI  - Peculiarities of the DNA of MM1, a temperate phage of Streptococcus pneumoniae.
AB  - The abundant presence of temperate phages in the chromosomes of clinical isolates
      of Streptococcus pneumoniae has been well documented. The genome of MM1, a
      temperate phage of pneumococcus, has been isolated as a DNA-protein complex. The
      protein is covalently bound to the DNA, was iodinated in vitro with Na125I, and
      has an Mr of 22,000. Electron microscopy and enzymatic analyses revealed that the
      MM1 genome is a linear, circularly permuted, terminally redundant collection of
      double-stranded DNA molecules packaged via a headful mechanism. The location of
      the pac site appears to be downstream of the terminase, between orf32 and orf34
      of the MM1 genome.

PMID- 15248163
TI  - An in vitro study of the susceptibility of mobile and cystic forms of Borrelia
      burgdorferi to tinidazole.
AB  - The susceptibility of mobile and cystic forms of Borrelia burgdorferi to
      tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ
      against the mobile spirochetes was >128 microg/ml at 37 degrees C in micro-oxic
      atmosphere when incubated for 14 days. TZ significantly reduced the conversion of
      mobile spirochetes to cystic forms during incubation. The MBC for older (10
      months-old) cysts at 37 degrees C in a micro-oxic atmosphere was >0.5 microg/ml,
      but >0.125 microg/ml for young (1-day-old) cysts. Acridine orange staining, dark
      field microscopy and transmission electron microscopy revealed that, when the
      concentration of TZ was > or = MBC, the contents of the cysts were partly
      degraded, core structures did not develop inside the young cysts, and the amount
      of RNA in these cysts decreased significantly. When cysts were exposed to TZ,
      both the spirochetal structures and core structures inside the cysts dissolved,
      and the production of blebs was significantly reduced. These observations may be
      valuable in the treatment of resistant infections caused by B. burgdorferi, and
      suggest that a combination of TZ and a macrolide antibiotic could eradicate both
      cystic and mobile forms of B. burgdorferi.

PMID- 15248164
TI  - Producing a scientific journal in a small scientific community: an author-helpful
      policy.

PMID- 15248165
TI  - Relationship between platelet count and bleeding risk in thrombocytopenic
      patients.
AB  - Platelets are lost from circulation by 2 mechanisms: senescence and random loss.
      Approximately 7.1 x 10(3) platelets/microL/d are postulated to be randomly used
      in maintaining vascular integrity. Thus, in clinically stable patients, major
      bleeding is unusual unless the platelet count is </=5 x 10(3)/microL. Risk
      factors for bleeding at higher platelet counts are disseminated intravascular
      coagulation with contributory clotting factor deficiencies, structural lesions
      with loss of vascular integrity, and refractoriness to platelet transfusions.
      Several large studies have documented the safety of lowering the prophylactic
      platelet transfusion trigger from the previously used 20 x 10(3)/microL to 10 x
      10(3)/microL. A few studies have even suggested that a 5 x 10(3)/microL trigger
      is acceptable. Based on these results, the next step of giving just therapeutic
      platelet transfusions is being evaluated. In a large retrospective study, the
      most significant predictor of bleeding was not the patient's platelet count but a
      history of bleeding in the prior 5 days. These data suggest that attention should
      be focused on providing aggressive platelet therapy for active bleeding rather
      than transfusing platelets prophylactically. Therapeutic platelet transfusions
      have been documented to control bleeding, and mortality rates are not increased
      when comparing patients receiving therapeutic to that seen in patients receiving
      prophylactic platelet transfusions.

PMID- 15248166
TI  - Leukoreduction filtration of blood with sickle cell trait.
AB  - Leukoreduction of cellular blood products by filtration has been shown to
      decrease the incidence of febrile nonhemolytic transfusion reactions,
      transmission of leukocyte-associated viruses, and HLA alloimmunization. However,
      the increasing popularity of leukofiltering blood products over the past few
      years has highlighted specific filtration failures associated with sickle trait
      (hemoglobin AS) blood. Sickle trait blood does not filter adequately, which leads
      to prolonged or incomplete filtration, often with a higher number of
      postfiltration leukocytes in the unit than the mandated minimal residual volume
      of <1 to 5 x 10(6). This review of the literature highlights various parameters
      that affect the adequacy of filtration of blood products, including effects of
      temperature, pH, osmolarity, type of anticoagulant, time of storage, and oxygen
      saturation of the blood unit. A combination of these factors likely contributes
      to the frequent filtration failure of sickle trait products. Although blood units
      are not routinely screened for sickle cell hemoglobin, administration of units
      with sickle trait red blood cells can be disadvantageous to certain patient
      populations. This review concludes with a discussion of different approaches to
      screening blood units for sickle cell trait.

PMID- 15248167
TI  - Informed consent for blood transfusion: should the possibility of prion risk be
      included?
AB  - The emergence of bovine spongiform encephalopathy (BSE) in British cattle has
      received significant media attention since its discovery in 1986. Transmission of
      this prion from cattle to humans has been documented, and the BSE prion is
      believed to be the causative agent for variant Creutzfeldt-Jakob disease (vCJD).
      Evidence of this spread is a significant threat to public health, and, although
      there has never been a proven case, there is a theoretical risk of transmission
      between humans by blood transfusions. In addition, recent animal studies have
      documented spread in this fashion, raising the question of whether vCJD should be
      included as part of informed consent for blood transfusions. The process of
      informed consent requires disclosure of material risks, defined as the risks that
      a reasonable person, under such circumstances, would want to know. Consent
      should, therefore, include the risks of a transfusion reaction, as well as the
      known infectious risks of blood. It should also include the unknown or
      theoretical risks of blood transfusions because full disclosure of even remote
      risks preserves the patient/physician trust relationship, which if breached, is
      very difficult to mend. Given the high level of public awareness, the potential
      lethality of the infection, and the theoretical risk of transmission by blood,
      vCJD can be considered a material risk, and consequently, it is reasonable to
      include it in the informed consent process.

PMID- 15248168
TI  - Fatalities caused by TRALI.
AB  - This article includes a retrospective review of fatalities caused by transfusion
      related acute lung injury (TRALI) over a 5-year period (from 1997 to 2002) that
      were reported to the Center for Biologics Evaluation and Research involving 58
      recipient deaths and the corresponding 63 blood component donors. Descriptive
      statistics are presented. Recipient characteristics include age, sex, and
      admitting diagnosis. Cardiovascular disease, pulmonary disorders, and cancer were
      the most frequent diagnoses of transfusion recipients. Reported deaths did not
      appear to be associated with age, sex, reason for transfusion, or transfusion
      component. Implicated blood component(s) and clinical symptoms at the time of
      reaction were recorded. Fresh frozen plasma was implicated in one half of the
      cases, whereas red blood cells played a role in approximately one third. The
      clinical characteristics described most often in TRALI reports included shortness
      of breath, frothy sputum, pulmonary infiltrates, and hypoxia. Donor variables
      included age, sex, parity, and laboratory tests for antibodies to HLA and/or
      antigranulocyte antibodies. Laboratory tests showed HLA antibodies and/or
      antigranulocyte antibodies were positive in the majority of donors tested. More
      data are needed to better describe the role of antibodies in these reactions.
      Greater awareness is crucial for the practitioner to be alert for signs and
      symptoms of TRALI and to be aware of the necessary steps in treatment.

PMID- 15248169
TI  - Dendritic cell-based immunotherapy for cancer and relevant challenges for
      transfusion medicine.
AB  - The encouraging results from dendritic cell-related cancer immunotherapy have
      created tremendous interest for its broad clinical application. Dendritic cells
      are the most potent antigen-presenting cells. In cancer patients, dendritic cell
      production and function along with other antitumor immune defenses are
      compromised. Autologous dendritic cells enriched and sensitized in vitro with
      tumor-associated antigens can effectively elicit host cellular immunity against
      cancer and result in clinical antitumor responses through either direct injection
      or ex vivo generation of antitumor T lymphocytes. In small group studies,
      clinical response rates have reached 50% in patients with advanced stage of
      cancer. These cellular products caused minimal side effects and were well
      tolerated. The isolation and preparation of clinical grade dendritic cells have
      been driven by transfusion medicine specialists who are well versed in similar
      processes for hematopoietic stem-cell preparation. The purpose of this article is
      to review the mechanisms of tumor immune surveillance and the biology of
      dendritic cells relevant to tumor antigen presentation, sensitization, and T
      lymphocyte stimulation. Information on tumor-associated antigens and clinical
      trial results with dendritic cell-based cancer immunotherapy are summarized. The
      potential challenges for blood banking/transfusion medicine involving both
      technical and regulatory issues are discussed.

PMID- 15248170
TI  - The structure and function of the molecules that carry human red blood cell and
      platelet antigens.
AB  - A number of molecules on the surface of red blood cells (RBCs) and platelets
      express antigenic activity. Various biochemical and molecular approaches have
      been used to determine the structure and possible function that these molecules
      have for their respective cell types. The existence of variant molecules and null
      phenotypes and the immunological response to these antigens have aided in the
      analysis of the structure and function relationships of these molecules. A
      comparison of the sequence to moieties of known function and the presence of
      functional domains for many of the molecules allows for a prediction of their
      function. The proposed function of the molecules that express RBC and platelet
      antigens includes membrane structure, transporter or channel formation,
      receptor/ligand signaling or adhesion, enzyme activity, and glycocalyx formation.
      However, the function of some of these molecules is not known, and many of the
      variant antigens do not show an obvious functional difference. For unknown
      reasons, some of these molecules are exceptionally polymorphic and the
      elucidation of the precise role that these polymorphisms play in structure and
      function is hindered by limitations in the in vitro and ex vivo analyses and
      access to precursor cell types. The objective of this review is to define the
      structure and function of those molecules that express RBC and platelet antigens
      and the significance, if any, that polymorphisms have for these molecules.

PMID- 15248173
TI  - Improving the bacteriological safety of platelet transfusions.

PMID- 15248179
TI  - Tumour necrosis factor alpha production by polymorphonuclear neutrophils treated
      with mouse anti-human CD19 monoclonal antibody.
AB  - Polymorphonuclear neutrophils (PMNs) play pivotal roles as phagocytic cells in
      immune defence against bacteria and parasites, exerting their effects by
      production of reactive oxygen species, several cytokines, chemokines and by
      phagocytotic reaction. In our investigation of properties of activated PMNs, we
      discovered that one of the two kinds of mouse anti-human CD19 monoclonal
      antibodies (mAbs) clone SJ25-C1, weakly binds to freshly prepared PMNs. Moreover,
      the treatment of freshly prepared PMNs with anti-CD19 mAb (clone SJ25-C1) at 37
      degrees C for 6 h induces the production and the secretion of tumour necrosis
      factor alpha (TNF alpha) by PMNs in vitro which was detectable in culture
      supernatants by bioassay using mouse cell line L929 cells. The concentration of
      TNF alpha secreted into the culture supernatant of PMNs cultured in the presence
      of anti-CD19 mAb (clone SJ25-C1) was higher than those of PMNs treated at 37
      degrees C for 6 h with various PMN activators, such as anti-CD24 mAb,
      granulocytes-macrophage colony stimulation factor (GM-CSF) or interferon gamma
      (IFN gamma). In contrast, another clone of anti-CD19 mAb, HD37, did not bind to
      freshly prepared PMNs and failed to produce TNF alpha. To confirm that anti-CD19
      mAb (clone SJ25-C1)-treated PMNs definitely produce TNF alpha, we measured the
      levels of intracellular expression of TNF alpha in PMNs permeabilized by saponin.
      These cells were treated with fluorescence-conjugated mouse anti-human TNF alpha
      mAb for detection of intracellular TNF alpha expression. Consequently, large
      amounts of intracellular TNF alpha were detected in PMNs treated with anti-CD19
      mAb (clone SJ25-C1) but not in those treated with anti-CD19 mAb (clone HD37).

PMID- 15248180
TI  - Plasma xanthine oxidase, superoxide dismutase and glutathione peroxidase
      activities and uric acid levels in severe and mild pre-eclampsia.
AB  - The aim of the present study was to measure plasma uric acid (UA) levels and
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase
      (XO) activities and to evaluate the relationship between these parameters and the
      severity of pre-eclampsia. Twenty-five pre-eclamptic, 15 healthy pregnant and 15
      non-pregnant women were enrolled in this study. Increased mean plasma XO activity
      was found to be higher in both pre-eclampsia groups than in the healthy pregnant
      group. Plasma UA levels were the highest in the severe pre-eclampsia group among
      the study groups. SOD and GSH-Px activities were significantly lower in both pre
      eclampsia groups than in the healthy pregnant group (p < 0.005 and p < 0.001,
      respectively). Increased XO and decreased SOD and GSH-Px activities may
      contribute to the pathophysiological mechanisms of pre-eclampsia and increased UA
      may serve a protective role responding to superoxide radicals arising from
      increased XO activity or other sources in pre-eclampsia.

PMID- 15248181
TI  - Effect of new and known 1,4-dihydropyridine derivatives on blood glucose levels
      in normal and streptozotocin-induced diabetic rats.
AB  - Analysis of the effect of several 1,4-DHP Ca(2+) channel antagonists on
      experimental and clinical diabetes shows that structurally similar Ca(2+) channel
      antagonists can exert opposite effects on Ca(2+) influx, glucose homeostasis and
      insulin secretion. The influence of the Ca(2+) channel antagonists on pancreatic
      beta cell functions is dependent on lipophilicity, interactions with the cell
      membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle
      membranes, with intracellular receptors, bioavailability and time of elimination
      from several organs and the bloodstream. In the present work we studied the
      effect at several doses of new compounds synthesized in the Latvian Institute of
      Organic Synthesis on blood glucose levels in normal and STZ-induced diabetic
      rats. The compounds tested were: 1,4-DHP derivatives cerebrocrast (1), etaftoron
      (2), OSI-1190 (3), OSI-3802 (4), OSI-2954 (5) and known 1,4-DHP derivatives:
      niludipine (6), nimodipine (7) and nicardipine (8) which possess different
      lipophilicities. Analysis of the structure-function relationships of the effect
      of 1,4-DHP derivatives on glucose metabolism showed that cerebrocrast could evoke
      qualitative differences in activity. Insertion of an OCHF(2) group in position 2
      of the 4-phenylsubstituent and propoxyethylgroup R in ester moieties in positions
      3 and 5 of the DHP structure, as well as an increase in the number of carbon
      atoms in the ester moiety, significantly modified the properties of the compound.
      Thereby cerebrocrast acquired high lipophilicity and membranotropic properties.
      Cerebrocrast, in a single administration at low doses (0.05 and 0.5 mg x kg(-1),
      p.o.), significantly decreased the plasma level of glucose in normal rats and in
      STZ-induced diabetic rats returned plasma glucose to basal levels. This effect
      was characterized by a slow onset and a powerful long-lasting influence on
      glucose metabolism, especially in STZ-induced diabetic rats.

PMID- 15248182
TI  - The effects of dietary flaxseed on the Fischer 344 rat: II. Liver gamma
      glutamyltranspeptidase activity.
AB  - The effect of 10% flax chow consumption from the 30th to the 130th day after
      birth was examined in male Fischer 344 rats. The effects of both the high
      lignan/high oil Norlin strain and a high lignan/low oil Solin strain of flaxseed
      were compared. Physically and behaviourally there were no differences in rats
      belonging to the three dietary groups at any time. At 50 and 100 days of dietary
      exposure, blood glucose levels were the same in Norlin and Solin flax chow-fed
      and as well as regular chow-fed rats; there were no signs of toxicity in the
      Norlin and Solin flax-fed rats since their plasma levels of alanine
      aminotransferase were the same and equal to those of regular chow-fed rats. The
      activity of gamma-glutamyltranspeptidase (gammaGT) displayed an increase in the
      liver homogenates of flax chow-fed rats. This increase was the same in Norlin and
      Solin flax-fed rats at 50 and 100 days. Thus the liver effect was not oil, but
      lignan, likely secoisolariciresinol diglucoside (SDG), induced and was effected
      early on, and sustained, after flax exposure. The degree of heat activation of
      liver homogenate gammaGT was the same in regular chow-fed and flax chow-fed rats.
      Compared to liver homogenate gammaGT activity, the soluble form of gammaGT was
      expressed at very low levels while the plasma membrane-bound form of gammaGT was
      expressed at very high levels in rat liver in both regular chow-fed and flax chow
      fed rats. There was no effect of flax feeding on the soluble form of liver
      gammaGT which was expressed at a very low level. Flax feeding effected an
      increase in the activity of gammaGT in isolated plasma membrane fractions which
      mirrored that in liver homogenates: the same degree of increase was seen in
      Norlin flax chow-fed and Solin flax chow-fed rats. Flax consumption effects an
      increase in the activity of liver gammaGT at the level of the plasma membrane
      which is lignan dependent, physiologically relevant and may be linked to
      hepatoprotection against injury through an increase in reduced glutathione.

PMID- 15248183
TI  - The effects of Maras powder (smokeless tobacco) on oxidative stress in users.
AB  - Maras Powder (MP) is a special kind of smokeless tobacco widely used in the
      southeast region of Turkey especially in Kahramanmaras and Gaziantep and other
      southeastern cities. It is obtained from a tobacco species, Nicotiana rustica L
      and ash of oak or grapevine wood. Tobacco may increase oxidative stress, which is
      related to the products of the oxygen metabolism taking place in all cells.
      Cellular antioxidants, e.g. catalase (CAT), superoxide dismutase (SOD) and
      glucose 6-phosphate dehydrogenase (G6PD) protect the cell against oxidative
      damage. An imbalance between the ROS and antioxidants in favour of ROS is
      described as oxidative stress. In this study, we aimed to investigate the effect
      of MP on antioxidant enzyme levels and lipid peroxidation. We measured
      malondialdehyde (MDA), CAT, SOD and G6PD levels in blood of 68 MP users and 30
      healthy controls who did not use MP. CAT, SOD and G6PD levels were lower in MP
      users than in the controls. On the other hand, lipid peroxidation levels (MDA),
      one of the best indicators of cytological damage, was increased in MP users
      compared with the controls. The present study showed that MP increases oxidative
      stress, which may cause many systemic disorders, including arteriosclerosis.

PMID- 15248184
TI  - AP-1 complexes mediate oxidized LDL-induced overproduction of TGF-beta(1) in rat
      mesangial cells.
AB  - Oxidized Low Density Lipoprotein (Ox-LDL)-induced overproduction of the
      prosclerotic cytokine transforming growth factor-beta1 (TGF-beta(1)) has been
      implicated in the pathogenesis of renal fibrosis and sclerosis. Because Ox-LDL
      increases TGF-beta(1) mRNA levels in rat mesangial cells, our investigation was
      designed to characterize these effects on the rat TGF-beta(1) promoter activity.
      We transfected luciferase reporter gene constructs containing TGF-beta(1) 5'
      flanking sequence (from -1550 to +57 bp) into mesangial cells. By assaying
      progressively deleted mutations in the promoter, we found two regions that were
      responsible for the induction. One is a negative regulatory region (-422 to -629)
      which represses the transcription of the TGF-beta(1) gene, the other is a
      positive regulatory region (-845 to -1550) which enhances the transcription unit
      efficiently. There is an activating protein-1(AP-1) binding site in the latter
      region. Mutagenesis in the AP-1 binding sites abolished the Ox-LDL effect.
      Furthermore, addition of the AP-1 inhibitor curcumin obliterated the Ox-LDL
      response. The Ox-LDL-induced TGF-beta(1) promoter activation was also prevented
      by inhibitors of protein kinase C, but not by p38 mitogen-activated protein
      kinase. Electrophoretic mobility shift assays with oligonucleotides containing AP
      1 binding sites showed that Ox-LDL treatment significantly enhanced the binding
      activity of nuclear proteins of mesangial cells. Supershift assays demonstrated
      that c-Jun was present in the protein-DNA complexes under stimulation of Ox-LDL.
      The functional and structural results show that Ox-LDL regulates rat TGF-beta(1)
      gene expression through AP-1 binding sites and gives rise to the involvement of
      protein kinase C in Ox-LDL-induced TGF-beta(1) gene expression.

PMID- 15248185
TI  - Cytoskeletal changes and the system of regulation of alkaline phosphatase
      activity in human periodontal ligament cells induced by mechanical stress.
AB  - The periodontal ligament (PDL) is a specialized, mechanically responsive tissue
      that adapts via cellular responses to equilibrate the effects of mechanical
      stress on teeth. However, the mechanism of remodelling by which individual cells
      in periodontal tissue detect and respond to mechanical stress is not well
      understood. To identify the cellular mechanisms induced by mechanical stress in
      the periodontal ligament, we examined the effects of cyclic stretching on
      periodontal ligament fibroblast-like cells (PDL cells). Furthermore, we
      investigated the effects of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)),
      and interaction with peripheral blood mononuclear cells (PBMCs) on mechanically
      simulated PDL cells. PDL cells were cultured on type I collagen-coated silicon
      membranes with 10% FBS alpha-MEM, and then subjected to cyclic mechanical
      stimulation (1 s stretching/1 s relaxation, 15% maximum elongation). Alkaline
      phosphatase activity was monitored by cytochemical and spectrophotometric
      methods. Morphologically, the cells assumed a spindle shape, and the cytoskeletal
      components, including microtubules and F-actin filaments, were aligned
      perpendicular to the strain force vector. Cyclic stretching decreased ALPase
      activity in PDL cells. The anabolic systemic hormone 1,25(OH)(2)D(3) increased
      ALPase activity, but this effect was suppressed by cyclic stretching. ALPase
      activities were reduced by co-culture with PBMCs, including lymphocytes and
      monocytes. This PBMC-induced ALPase reduction was synergistically reduced by
      cyclic stretching. ALPase activity was decreased by co-culture with PBMCs, and
      ALPase activity was reduced synergistically by treatment with PBMCs and cyclic
      stretching. We conclude that PDL cells changed their shape and alignment in
      response to cyclic stretching. Furthermore, local factors, such as mechanical
      stress and PBMCs, showed synergistic suppressive effects on ALPase activity.

PMID- 15248186
TI  - Variability in the expression of urokinase receptor (CD87) mutants on cells:
      relevance to cell adhesion.
AB  - The urokinase-type plasminogen activator receptor (uPAR, CD87) is a
      glycosylphosphatidylinositol (GPI)-anchored protein, containing three homologous
      Ly-6 domains, that mediates integrin-independent cell adhesion by directly
      binding to extracellular matrix protein vitronectin (VN). To elucidate the
      structural requirements for the uPAR-dependent cell adhesion on VN, several
      glycolipid-anchored variants of uPAR were expressed in BAF3 cells, (mouse pre B
      lymphocytes) followed by functional analysis. The individual domains of uPAR were
      expressed at very low levels, the two domain mutants were expressed to a higher
      level and the wild type uPAR was expressed highly. Point mutations in domain 2 of
      uPAR have been shown to diminish cellular binding of the ligand urokinase and we
      observed a lack of VN binding to this mutant. Flow cytometry with a number of
      monoclonal antibodies indicated that the domain-specific antigenic determinants
      in these mutants were well preserved. Only the cells expressing the intact uPAR
      with all three domains adhered strongly to a VN substrate, whereas none of the
      other transfected cells showed significant cell adhesion. Hence, any alterations
      in the domain structure of uPAR reduce its expression and only the intact
      receptor can sustain the direct cell adhesion on VN-rich matrices found at sites
      of inflammation and injury.

PMID- 15248187
TI  - Antioxidant-associated chemoprevention by sodium selenite in N
      nitrosodiethylamine-induced and phenobarbital-promoted hepatocarcinogenesis in
      rats.
AB  - The anticarcinogenic/antioxidant potential of sodium selenite (Se), a
      micronutrient, was evaluated on liver tumourigenesis induced by N
      nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet).
      Male, albino rats of the Wistar strain were exposed intravenously to a single
      dose of DEN (200 mg x kg(-1) body weight). Se (4 ppm in drinking water) was
      supplemented before initiation, or during initiation and/or during the promotion
      period of carcinogenesis. At the end of 16 weeks (after DEN administration)
      nodular incidence, the total number of nodules and non-enzymic antioxidants such
      as vitamin E, vitamin C, total thiol, protein thiol and non-protein thiol
      contents were measured in hepatoma, surrounding tissue and kidney tissue of
      control and experimental groups. In hepatoma-bearing animals the above
      biochemical changes were decreased when compared with normal control animals. On
      Se treatment throughout the study, (20 weeks) the above biochemical changes
      reverted to normal levels. Pre- and post-treatment with Se also shows a tendency
      to reverse the above changes. The results indicate that prior application of Se
      significantly reverses the adverse changes produced during the tumourigenesis.
      Furthermore, prior applications of Se significantly reduced the cumulative number
      of tumours per tumour-bearing animals. The present study reveals the antitumour
      potential of Se against DEN-induced liver carcinogenesis.

PMID- 15248189
TI  - Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and
      Nizoral) in a healthy female Mexican population.
AB  - A randomized, crossover study was conducted in 24 healthy female volunteers to
      compare the bioavailability of two brands of ketoconazole (200 mg) tablets;
      Onofin-K (Farmaceuticos Rayere S.A., Mexico) as the test and Nizoral (Janssen
      Cilag, Mexico) as the reference products. The study was performed at the Clinical
      Pharmacology Research Center of the Hospital General de Mexico in Mexico City.
      Two tablets (400 mg) were administered as a single dose with 250 ml of water
      after a 12 h overnight fast on two treatment days separated by a 1 week washout
      period. After dosing, serial blood samples were collected for a period of 12 h.
      Plasma harvested was analysed for ketoconazole by a modified and validated HPLC
      method with UV detection in the range 400-14000 ng/ml, using 200 microl of plasma
      in a full-run time of 2.5 min. The pharmacokinetic parameters AUC(0-t), AUC(0
      alpha), Cmax, Tmax and t(1/2) were determined from plasma concentrations of both
      formulations and the results discussed. AUC(0-t), AUC(0-alpha) and Cmax were
      tested for bioequivalence after log transformation of data, and no significant
      differences were found either in 90% classic confidence interval or in the
      Anderson and Hauck test (p < 0.05). Based on statistical analysis, it is
      concluded that Onofin-K is bioequivalent to Nizoral.

PMID- 15248188
TI  - Topical disposition of two strengths of a 125I-rhEGF jelly in rat skin wounds.
AB  - Growth factors have proved to be an effective therapeutic strategy. However, some
      controversies have arisen concerning their efficacy in topical wound treatments.
      Stabilization of epidermal growth factors at the wound site and long-lasting
      receptor occupancy are important factors for wound repair. This study evaluated
      the cumulative profiles of two jellies containing 10 or 20 microg of 125I-rhEGF
      per gram of jelly, in a rat full-thickness skin lesion model. The prolonged time
      courses at the wound sites for both strengths compared with saline solutions
      previously evaluated using a similar skin lesion model are reported. It seems
      that these two topical formulations that provide more sustained amounts of 125I
      rhEGF over the period of sampling, would probably achieve the required wound
      healing response in terms of cell proliferation, collagen deposition and protein
      synthesis. Further studies need to be developed in order to elucidate whether
      such an in vivo disposition pattern is consistent with an earlier and stronger
      promotion of wound healing events.

PMID- 15248190
TI  - Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics
      of the same total dose of torasemide in rabbits.
AB  - The pharmacokinetics and pharmacodynamics of torasemide were evaluated after
      intravenous administration of the same total dose of torasemide at a dose of
      1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min
      (treatment II) and 2 h (treatment III). The loss of water and electrolytes in
      urine induced by torasemide was immediately replaced with infusion of an equal
      volume of lactated Ringer's solution. All the pharmacokinetic parameters of
      torasemide, such as total area under the plasma concentration-time curve from
      time zero to time infinity (AUC), total body clearance (CL), apparent volume of
      distribution at steady state (Vss), terminal half-life and mean residence time
      (MRT), were independent of infusion times. However, the 8 h urine output (235,
      534 and 808 ml) and 8 h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol)
      and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments
      II and III than those in treatment I, although the total 8 h urinary excretion of
      unchanged torasemide (1210, 1210 and 1310 microg) were not significantly
      different among the three treatments. This could be due to the higher diuretic
      efficiencies in treatments II and III.

PMID- 15248191
TI  - Pharmacodynamics of controlled release verapamil in patients with hypertension:
      an analysis using spline functions.
AB  - AIMS: To use a nonparametric approach involving longitudinal splines to model the
      baseline blood pressure profile and investigate the impact of this modelling on
      the pharmacodynamic analysis for verapamil in patients with angina or
      hypertension. METHODS: Dose ranging studies were conducted in patients with
      hypertension and with angina. Subjects received doses of 120, 180, 360 or 540 mg
      racemic verapamil. Pharmacodynamic data were created by subtracting the
      (systolic) blood pressure following active drug from the placebo response, either
      by direct subtraction or after modelling the baseline with a longitudinal spline
      model fitted to the placebo data by nonlinear mixed effects modelling. An Emax
      model was then used to describe the relationship between change in blood pressure
      and (R-)verapamil plasma concentration. RESULTS: The maximum decrease in systolic
      blood pressure was found to be 57.6 (+/- 26.1) mm and the C50 was 420 (+/- 349)
      microg/l for the data obtained by direct subtraction of the placebo data. Similar
      results were obtained when a cubic spline model was used to describe each
      individual's placebo response. However, the use of a population spline model only
      allowed a linear pharmacodynamic model to be fitted to the resulting data. Sparse
      data were created by randomly removing 66% of the data from the placebo and
      active phases. The population spline model gave very similar parameter estimates
      for the linear model applied to the sparse data to those obtained from the
      complete data set. CONCLUSIONS: The use of a longitudinal spline model together
      with nonlinear mixed effects modelling to account for baseline blood pressure
      response can be very powerful in a sparse data environment.

PMID- 15248192
TI  - DM27, an enaminone, modifies the in vitro transport of antiviral therapeutic
      agents.
AB  - OBJECTIVE: For most antiviral drugs, low or variable bioavailability is
      attributed to poor absorption, susceptibility to efflux, or first pass
      metabolism. Enaminones are beta dicarbonyl compounds, which display P
      glycoprotein (P-gp) substrate properties with high efflux ratios. This study
      investigates the influence of DM27, an enaminone, on the in vitro transport of
      antiviral agents and the possibility of using DM27 as a P-gp inhibitor to prevent
      the efflux of certain antiretroviral agents. METHODS: The transport of
      [3H]amprenavir, [3H]saquinavir, [3H]ritonavir, [14C]zidovudine (AZT) and
      [3H]acyclovir was evaluated across Caco-2 cells with DM27 (10(-10)-10(-4) M). In
      addition, the effect of DM27 (10(-6) M) on the transport of transcellular and
      paracellular markers was tested to evaluate its influence on these transport
      pathways. The apparent permeability coefficient (Papp) for each drug or marker
      was calculated with/without DM27 and toxicity evaluation for DM27 was performed
      using the MTS assay. RESULTS: The mean Papp for the investigated antiviral agents
      significantly increased by 22%-51% after DM27 incubation without any toxicity to
      the Caco-2 cells. In addition, DM27 did not influence the transcellular or
      paracellular transport of propranolol and mannitol, respectively. CONCLUSIONS:
      DM27, an enaminone, increased the transport of antiretroviral drugs and acyclovir
      in a nontoxic manner without affecting the paracellular or transcellular
      transport of these drugs. This study suggests that DM27 may be used as a P-gp
      efflux inhibitor to enhance the oral bioavailability of antiviral drugs and that
      drug-drug interactions will most probably be encountered upon co-administration
      of P-gp substrate drugs with enaminones.

PMID- 15248193
TI  - The toppler mouse: a novel mutant exhibiting loss of Purkinje cells.
AB  - We describe the genetic and neurological features of toppler, a spontaneous
      autosomal mutation that appeared in a colony of FVB/N mice and that manifests as
      severe ataxia appearing at around 12 days of age, worsening with age. The
      lifespan of affected mice is 8-12 months, with occasional mice living longer.
      Both homozygous males and females are fertile, and females are able to nurture
      litters. Histological examination of brain revealed no striking abnormalities
      other than the loss of cerebellar Purkinje cells. The toppler mutation was mapped
      to mouse chromosome 8, and to assess whether it was novel or a recurrence of a
      previously described chromosome 8 mouse mutant, toppler mice were crossed with
      the nervous and tottering mouse mutants. These studies demonstrate that toppler
      is a unique mouse mutation. Purkinje cell abnormalities in toppler mice were
      obvious around postnatal day (P) 14, i.e., toppler Purkinje cells already
      exhibited abnormal morphology. Staining for calbindin, a calcium binding protein
      enriched in Purkinje cells, showed altered dendritic morphology. Between P14 and
      P30, dramatic Purkinje cell loss occurred, although there were differences in the
      degree of Purkinje cell loss in each lobule. At P30, the surviving Purkinje cells
      expressed zebrin II. From P30 through 6 months, many of the remaining Purkinje
      cells gradually degenerated. Purkinje cell loss was analyzed by terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL),
      and Purkinje cells were TUNEL-positive most abundantly at P21. In addition,
      Bergmann glia were TUNEL positive at P21, and they expressed activated caspase-3
      at earlier time points. Interestingly, despite the apparent death of some
      Bergmann glia, there was up-regulation of glial fibrillary acidic protein,
      expressed in astrocytes as well as Bergmann glia. Given the changes in both
      Purkinje cells and glia in toppler cerebellum, this may be a very useful model in
      which to investigate the developmental interaction of Purkinje cells and Bergmann
      glia.

PMID- 15248194
TI  - Effects of limb exercise after spinal cord injury on motor neuron dendrite
      structure.
AB  - An integration center subserving locomotor leg movements resides in the upper
      lumbar spinal cord. If this neuronal network is preserved after a spinal cord
      injury, it is possible to stimulate this circuitry to initiate and promote
      walking. The several effective approaches (electrical stimulation, pharmacologic
      agents, physical therapy training programs) may all share a common modus operandi
      of altering synaptic activity within segmental spinal cord. To understand the
      neural substrate for the use-dependent behavioral improvement, we studied the
      dendritic architecture of spinal motor neurons. In the first experiment, we
      compared three groups of animals: animals with an intact spinal cord, animals
      that had a complete spinal cord transection (SCT) and animals with SCT who
      engaged in a daily exercise program of actively moving paralyzed hindlimbs
      through the motions of walking. When compared with animals with an intact spinal
      cord, the motor neurons from animals with SCT displayed marked atrophy, with loss
      of dendritic membrane and elimination of branching throughout the visible tree
      within transverse tissue slices. None of these regressive changes were found in
      the motor neurons from SCT animals that underwent exercise. In a second
      experiment, we inquired whether exercise of animals with an intact spinal cord
      influenced dendrite structure. Increased exercise had very modest effects on
      dendrite morphology, indicating an upper limit of use-dependent dendrite growth.
      Our findings suggest that the dendritic tree of motor neurons deprived of
      descending influences is rapidly pruned, and this finding is not observed in
      motor neurons after SCT if hindlimbs are exercised. The functional benefits of
      exercise after SCT injury may be subserved, in part, by stabilizing or remodeling
      the dendritic tree of motor neurons below the injury site.

PMID- 15248195
TI  - Retinal target cells of the centrifugal projection from the isthmo-optic nucleus.
AB  - Although the avian retina has long been known to receive projection from a
      midbrain nucleus, the isthmo-optic nucleus (ION), the output of its target cells
      has remained obscure. We labeled the isthmo-optic (IO) terminals in the Japanese
      quail retina, by using anterograde transport of fluorescent tracer injected into
      the ION, and then labeled target cells for these terminals by means of
      intracellular tracer injection under direct microscopic observation. Somata of
      the IO target cells (IOTCs) lie in the innermost zone of the inner nuclear layer
      of the ventral half of the retina and have no dendrites but an axon. The axons
      run in the inner plexiform layer (IPL) for up to 6 mm and terminate densely in a
      round or elliptical terminal field, about 90-290 microm in diameter, of the
      outermost zone of the IPL. Longer axons (> 2 mm) extend dorsally, but shorter
      ones (< 1 mm) project ventrally or horizontally, so the terminals are distributed
      widely in both dorsal and ventral halves of the retina. The IOTCs cannot be
      classified into any of the five conventional major classes of retinal cells,
      including amacrine cells, and are thought to be "slave" neurons whose output is
      controlled by the neurons in the brain. Topographic separation between input to
      and output from the IOTCs by the axons might be essential for the overall
      topographic organization of the centrifugal visual system in birds.

PMID- 15248196
TI  - Active caspase-3 expression during postnatal development of rat cerebellum is not
      systematically or consistently associated with apoptosis.
AB  - Development is a dynamic process that includes an intricate balance between an
      increase in cell mass and an elimination of excess or defective cells. Although
      caspases have been intimately linked to apoptotic events, there are a few reports
      suggesting that these cysteine proteases can influence the differentiation and
      proliferation of cells. Specifically, the active form of caspase-3, which has
      been classified as an executor of apoptosis, recently has been implicated in a
      nonapoptotic role in the regulation of the cell cycle, cell proliferation, and
      cell differentiation. This study investigated the nonapoptotic function and
      phenotypic expression of active caspase-3-positive cells in the external granule
      cell layer (EGL) of the postnatal rat cerebellum by using biochemical and
      immunohistochemical analyses, respectively. Evidence that negates an apoptotic
      function for the caspase-3-positive EGL cells includes a failure to exhibit
      chromatin condensation (assessed with TOPRO), phosphatidyl serine externalization
      (Annexin V labeling), or DNA fragmentation (TUNEL labeling). Proliferative (Ki67
      positive) and differentiated (TUJ1-positive) cells within the EGL exhibited a
      cytosolic expression of caspase-3, whereas terminally differentiated granule
      cells (NeuN-positive) in the internal granular layer and the migrating granule
      cells did not express active caspase-3. Thus, this study supports a nonapoptotic
      role for active caspase-3 in cells residing in the EGL and suggests a possible
      involvement in EGL proliferation and differentiation.

PMID- 15248197
TI  - Target-specific differences in somatodendritic morphology of layer V pyramidal
      neurons in rat motor cortex.
AB  - Dendritic geometry has been shown to be a critical determinant of information
      processing and neuronal computation. However, it is not known whether cortical
      projection neurons that target different subcortical nuclei have distinct
      dendritic morphologies. In this study, fast blue retrograde tracing in
      combination with intracellular Lucifer yellow injection and diaminobenzidine
      (DAB) photoconversion in fixed slices was used to study the morphological
      features of corticospinal, corticostriatal, and corticothalamic neurons in layer
      V of rat motor cortex. Marked differences in the distribution of soma, somal
      size, and dendritic profiles were found among the three groups of pyramidal
      neurons. Corticospinal neurons were large, were located in deep layer V, and had
      the most expansive dendritic fields. The apical dendrites of corticospinal
      pyramidal neurons were thick, spiny, and branched. In contrast, nearly all
      corticostriatal neurons were small cells located in superficial layer V. Their
      apical dendritic shafts were significantly more slender, though spiny like those
      of corticospinal neurons. Corticothalamic neurons, which were located in
      superficial layer V and in layer VI, had small or medium-sized soma, slender
      apical dendritic shafts, and dendrites that were largely spine free. This study
      indicates that, in layer V of rat motor cortex, each population of projection
      neurons has a unique somatodendritic morphology and suggests that distinct modes
      of cortical information processing are operative in corticospinal,
      corticostriatal, and corticothalamic neurons.

PMID- 15248198
TI  - Evidence for the disproportionate mapping of olfactory airspace onto the main
      olfactory bulb of the hamster.
AB  - Olfactory receptor neurons (ORNs) project to the rodent main olfactory bulb (MOB)
      from spatially distinct air channels in the olfactory recesses of the nose. The
      relatively smooth central channels of the dorsal meatus map onto the dorsal MOB,
      whereas the highly convoluted peripheral channels of the ethmoid turbinates
      project to the ventral MOB. Medial and lateral components of each projection
      stream innervate the medial and lateral MOB, respectively. To ascertain whether
      such topography entails the disproportionate representation seen in other sensory
      maps, we used disector-based stereological techniques in hamsters to estimate the
      number of ORNs associated with each channel in the nose and the number of their
      targets (glomeruli and mitral and tufted cells) in corresponding divisions of the
      MOB. Each circumferential half of the MOB (dorsal/ventral, medial/lateral)
      contained about 50% of the 3,100 glomeruli and about 50% of the 160,000 mitral
      and tufted cells per bulb. We found equivalent numbers of ORNs with dendritic
      knobs in the medial and lateral channels (4.5 million each). However, the central
      channels had only 2 million knobbed ORNs, whereas the peripheral channels had 7
      million. Thus, there is a disproportionate mapping of the central-peripheral axis
      of olfactory airspace onto the dorsal-ventral axis of the MOB, encompassing a
      greater than threefold variation in the average convergence of ORNs onto MOB
      secondary neurons. We hypothesize that the disproportionate projections help to
      optimize chemospecific processing by compensating, with differing sensitivity,
      for significant variation in the distribution and concentration of odorant
      molecules along the olfactory air channels during sniffing.

PMID- 15248200
TI  - Therapeutic cocktails for rheumatoid arthritis: the mixmaster's guide.

PMID- 15248201
TI  - Bisphosphonates: environmental protection for the joint?

PMID- 15248202
TI  - Biomarkers in systemic lupus erythematosus: II. Markers of disease activity.

PMID- 15248203
TI  - Associations, populations, and the truth: recommendations for genetic association
      studies in Arthritis & Rheumatism.

PMID- 15248204
TI  - Retardation of joint damage in patients with early rheumatoid arthritis by
      initial aggressive treatment with disease-modifying antirheumatic drugs: five
      year experience from the FIN-RACo study.
AB  - OBJECTIVE: To evaluate the long-term frequency of disease remissions and the
      progression of joint damage in patients with early rheumatoid arthritis (RA) who
      were initially randomized to 2 years of treatment with either a combination of 3
      disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: In
      this multicenter prospective followup study, a cohort of 195 patients with early,
      clinically active RA was randomly assigned to treatment with a combination of
      methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a
      single DMARD (initially, sulfasalazine) with or without prednisolone. After 2
      years, the DMARD and prednisolone treatments became unrestricted, but were still
      targeted toward remission. The long-term effectiveness was assessed by recording
      the frequency of remissions and the extent of joint damage seen on radiographs of
      the hands and feet obtained annually up to 5 years. Radiographs were assessed by
      the Larsen score. RESULTS: A total of 160 patients (78 in the combination group
      and 82 in the single group) completed the 5-year extension study. At 2 years, 40%
      of the patients in the combination-DMARD group and 18% in the single-DMARD group
      had achieved remission (P < 0.009). At 5 years, the corresponding percentages
      were 28% and 22% (P not significant). The median Larsen radiologic damage scores
      at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD
      groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001),
      respectively. CONCLUSION: Aggressive initial treatment of early RA with the
      combination of 3 DMARDs for the first 2 years limits the peripheral joint damage
      for at least 5 years. Our results confirm the earlier concept that triple therapy
      with combinations of DMARDs contributes to an improved long-term radiologic
      outcome in patients with early and clinically active RA.

PMID- 15248205
TI  - The relationship between disease activity and radiologic progression in patients
      with rheumatoid arthritis: a longitudinal analysis.
AB  - OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the
      consequence of persistent inflammatory activity. To determine whether a change in
      disease activity is related to a change in radiologic progression in individual
      patients, we investigated the longitudinal relationship between inflammatory
      disease activity and subsequent radiologic progression. METHODS: The databases of
      the University Medical Center Nijmegen (UMCN) cohort and the Maastricht
      Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN
      cohort included 185 patients with early RA who were followed up for up to 9
      years. Patients were assessed every 3 months for disease activity and every 3
      years for radiologic damage. The COBRA cohort included 152 patients with early RA
      who were followed up for up to 6 years. Patients were assessed at least every
      year for disease activity and every 12 months for radiologic damage. Disease
      activity was assessed with the Disease Activity Score (DAS) (original DAS in the
      UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the
      Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal
      regression analysis (generalized estimating equations [GEE]), using
      autoregression for longitudinal associations and radiologic damage as the
      dependent variable. Time, time(2) baseline predictors for radiologic progression
      and their interactions with time, as well as DAS/DAS28 (actual values or interval
      means and interval SDs of the means) were subsequently modeled as explanatory
      variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic
      progression over time (regression coefficient for time(2) -1.0 [95% confidence
      interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8,
      0.0] in the COBRA cohort). After adjustment for time effects and baseline
      predictors of radiologic progression and their interactions with time, a positive
      longitudinal relationship was indicated by autoregressive GEE between the mean
      interval DAS and radiologic progression in the UMCN cohort (regression
      coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and
      radiologic progression in the COBRA cohort (regression coefficient 1.4 [95%
      confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval
      DAS was independently longitudinally related to the radiologic progression over
      the same periods (regression coefficient 20.2 [95% confidence interval 7.2,
      33.3]). In both cohorts, the longitudinal relationships between (fluctuations in)
      disease activity and radiologic progression were found selectively in rheumatoid
      factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear
      in individual patients. Fluctuations in disease activity are directly related to
      changes in radiologic progression, which supports the hypothesis that disease
      activity causes radiologic damage. This relationship might only exist in RF
      positive patients.

PMID- 15248206
TI  - Diagnostic value of magnetic resonance imaging of the forefeet in early
      rheumatoid arthritis when findings on imaging of the metacarpophalangeal joints
      of the hands remain normal.
AB  - OBJECTIVE: To investigate the diagnostic role of magnetic resonance imaging (MRI)
      of the forefeet in patients with early rheumatoid arthritis (RA) in whom findings
      on MR images of the hands are normal and conventional radiographs of the hands
      and feet do not show erosions. METHODS: The study group comprised 25 patients
      with early RA (disease duration of <12 months) in whom erosions were not
      demonstrated on conventional radiographs of the hands and feet. These patients
      underwent MRI of the clinically dominant hand to detect signs of arthritis. If
      results of MRI of the hand were normal according to the Outcome Measures in
      Rheumatology Clinical Trials (OMERACT) RA-MRI scoring system (RAMRIS), MRI of the
      dominant forefoot was performed. The MRI protocol comprised coronal and sagittal
      T1-weighted spin-echo (before and after administration of contrast medium),
      coronal fat-suppressed short tau inversion recovery sequences, coronal and
      sagittal T2-weighted turbo spin-echo sequences, and axial fat-suppressed T1
      weighted spin-echo sequences after administration of contrast medium. MRI of the
      forefeet was analyzed on the basis of a modified RAMRIS. RESULTS: MRI revealed
      pathologic findings in the hands of 15 of 25 patients (edema in 9 patients,
      synovitis in 12, erosions in 6, defects in 3). In 10 patients with a mean disease
      duration of 9.4 weeks, hand MRI scans were normal according to RAMRIS. Four of
      these 10 patients had tenosynovitis of the finger flexor tendons (there was no
      OMERACT criterion for tenosynovitis). RAMRIS analysis of the corresponding MRI
      scans of the forefeet of these patients revealed signs of edema in 7 patients,
      synovitis in all 10 patients (at the third metatarsophalangeal [MTP] joint in 7,
      at the fourth MTP joint in 6, at the first MTP joint in 4, and at the fifth MTP
      joint in 2 patients), tenosynovitis of the foot flexor tendons in 2 patients,
      erosions at the second and third MTP joints in 1 patient, and a single defect at
      the first MTP joint in 1 patient. CONCLUSION: RAMRIS analysis of MRI scans of the
      forefeet detected synovitis and bone edema in patients with early RA in whom MRI
      of the finger joints was normal. MRI of the forefeet contributes an additional
      tool aimed at earlier and more accurate diagnosis and thus might allow an earlier
      decision to start appropriate medication in patients with early RA.

PMID- 15248207
TI  - Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis:
      comparison with magnetic resonance imaging, conventional radiography, and
      clinical examination.
AB  - OBJECTIVE: To compare ultrasonography (US) with magnetic resonance imaging (MRI),
      conventional radiography, and clinical examination in the evaluation of bone
      destruction and signs of inflammation in the metatarsophalangeal (MTP) joints of
      patients with rheumatoid arthritis (RA). METHODS: Two hundred MTP joints of 40
      patients with RA and 100 MTP joints of 20 healthy control subjects were assessed
      with B-mode US, contrast-enhanced MRI, conventional radiography, and clinical
      examination for signs of bone destruction and joint inflammation. RESULTS: With
      MRI considered the reference method, the sensitivity, specificity, and accuracy
      of US for the detection of bone erosions were 0.79, 0.97, and 0.96, respectively,
      while the corresponding values for radiography were 0.32, 0.98, and 0.93. The
      sensitivity, specificity, and accuracy of US for the detection of synovitis were
      0.87, 0.74, and 0.79, while for clinical examination, the corresponding values
      were 0.43, 0.89, and 0.71. Erosive disease was identified in 26 patients by US,
      compared with 20 patients by MRI and 11 patients by radiography. Evaluation by US
      indicated signs of inflammation in 36 patients, while MRI and clinical
      examination revealed signs of inflammation in 31 patients and 20 patients,
      respectively. US and MRI volume-based gradings of synovitis showed intraclass
      correlation coefficients of 0.56-0.72 (P < 0.0001). The MRI and radiographic
      visualizations of US-detected bone changes were closely related to their size
      based gradings on US. CONCLUSION: US enables detection and grading of destructive
      and inflammatory changes in the MTP joints of patients with RA. By comparison
      with MRI, US was found to be markedly more sensitive and accurate than clinical
      examination and conventional radiography. Considering the early and frequent
      involvement of the MTP joints, evaluation of these joints by US may be of major
      clinical importance in RA.

PMID- 15248208
TI  - Association between HLA class II genes and autoantibodies to cyclic citrullinated
      peptides (CCPs) influences the severity of rheumatoid arthritis.
AB  - OBJECTIVE: The functional role of HLA class II molecules in the pathogenesis of
      rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the
      interaction between T and B lymphocytes required for long-lived B cell responses
      and generation of high-affinity IgG antibodies. We undertook this study to
      investigate the relationship between HLA class II gene polymorphisms and RA
      specific IgG antibodies against cyclic citrullinated peptides (anti-CCP
      antibodies). METHODS: High-resolution HLA-DR and DQ typing and anti-CCP-2
      antibody testing were performed on 268 RA patients from the Early Arthritis
      Clinic cohort at the Department of Rheumatology of the Leiden University Medical
      Center. The presence of anti-CCP antibodies was analyzed in carriers of the
      different DR and DQ alleles. Disease progression was measured over a period of 4
      years by scoring radiographs of the hands and feet using the Sharp/van der Heijde
      method. RESULTS: Carriership of the individual alleles HLA-DRB1*0401, DRB1*1001,
      DQB1*0302, and DQB1*0501 was associated with the presence of anti-CCP antibodies.
      Carriers of DQ-DR genotypes containing proposed RA susceptibility alleles were
      significantly more often anti-CCP antibody positive. Carriership of one or two
      HLA-DRB1 shared epitope (SE) alleles was significantly associated with production
      of anti-CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8
      6.0 and OR 13.3, 95% CI 4.6-40.4, respectively). An increased rate of joint
      destruction was observed in SE+, anti-CCP+ patients (mean Sharp score 7.6 points
      per year) compared with that in SE-, anti-CCP+ patients (2.4 points per year) (P
      = 0.04), SE+, anti-CCP- patients (1.6 points per year) (P < 0.001), and SE-, anti
      CCP- patients (1.6 points per year) (P < 0.001). CONCLUSION: HLA class II RA
      susceptibility alleles are associated with production of anti-CCP antibodies.
      Moreover, more severe disease progression is found in RA patients with both anti
      CCP antibodies and SE alleles.

PMID- 15248209
TI  - Dissection of class III major histocompatibility complex haplotypes associated
      with rheumatoid arthritis.
AB  - OBJECTIVE: We have previously identified a single-nucleotide polymorphism (SNP)
      haplotype involving the lymphotoxin alpha (LTA) and tumor necrosis factor (TNF)
      loci (termed haplotype LTA-TNF2) on chromosome 6 that shows differential
      association with rheumatoid arthritis (RA) on HLA-DRB1*0404 and *0401 haplotypes,
      suggesting the presence of additional non-HLA-DRB1 RA susceptibility genes on
      these haplotypes. To refine this association, we performed a case-control
      association study using both SNPs and microsatellite markers in haplotypes
      matched either for HLA-DRB1*0404 or for HLA-DRB1*0401. METHODS: Fourteen SNPs
      lying between HLA-DRB1 and LTA were genotyped in 87 DRB1*04-positive families.
      High-density microsatellite typing was performed using 24 markers spanning 2,500
      kb centered around the TNF gene in 305 DRB1*0401 or *0404 cases and 400 DRB1*0401
      or *0404 controls. Single-marker, 2-marker, and 3-marker minihaplotypes were
      constructed and their frequencies compared between the DRB1*0401 and DRB1*0404
      matched case and control haplotypes. RESULTS: Marked preservation of major
      histocompatibility complex haplotypes was seen, with chromosomes carrying LTA
      TNF2 and either DRB1*0401 or DRB1*0404 both carrying an identical SNP haplotype
      across the 1-Mb region between TNF and HLA-DRB1. Using microsatellite markers, we
      observed two 3-marker minihaplotypes that were significantly overrepresented in
      the DRB1*0404 case haplotypes (P = 0.00024 and P = 0.00097). CONCLUSION: The
      presence of a single extended SNP haplotype between LTA-TNF2 and both DRB1*0401
      and DRB1*0404 is evidence against this region harboring the genetic effects in
      linkage disequilibrium with LTA-TNF2. Two RA-associated haplotypes on the
      background of DRB1*0404 were identified in a 126-kb region surrounding and
      centromeric to the TNF locus.

PMID- 15248210
TI  - Sulfasalazine is a potent inhibitor of the reduced folate carrier: implications
      for combination therapies with methotrexate in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether interactions of sulfasalazine (SSZ) with
      reduced folate carrier (RFC), the dominant cell membrane transporter for natural
      folates and methotrexate (MTX), may limit the efficacy of combination therapy
      with MTX and SSZ in patients with rheumatoid arthritis. METHODS: Human RFC
      (over)expressing CEM cells of T cell origin were used to analyze the effect of
      SSZ on the RFC-mediated cellular uptake of radiolabeled MTX and the natural
      folate leucovorin. Moreover, both cells with and those without acquired
      resistance to SSZ were used to assess the antiproliferative effects of MTX in
      combination with SSZ. RESULTS: Transport kinetic analyses revealed that SSZ was a
      potent noncompetitive inhibitor of RFC-mediated cellular uptake of MTX and
      leucovorin, with mean +/- SD K(i) (50% inhibitory concentration) values of 36 +/-
      6 microM and 74 +/- 7 microM, respectively. Consistent with the inhibitory
      interaction of SSZ with RFC, a marked loss of MTX efficacy was observed when MTX
      was coadministered with SSZ: up to 3.5-fold for CEM cells in the presence of 0.25
      mM of SSZ, and >400-fold for SSZ-resistant cells in the presence of 2.5 mM of
      SSZ. Importantly, along with diminished efficacy of MTX, evidence for cellular
      folate depletion was obtained by the demonstration of an SSZ dose-dependent
      decrease in leucovorin accumulation. CONCLUSION: At clinically relevant plasma
      concentrations, interactions of SSZ with RFC provide a biochemical rationale for
      2 important clinical observations: 1) the onset of (sub)clinical folate
      deficiency during SSZ treatment, and 2) the lack of additivity/synergism of the
      combination of SSZ and MTX when these disease-modifying antirheumatic drugs are
      administered simultaneously. Thus, when considering use of these drugs in
      combination therapies, the present results provide a rationale both for the use
      of folate supplementation and for spacing administration of these drugs over
      time.

PMID- 15248212
TI  - Elevation of activated protein C in synovial joints in rheumatoid arthritis and
      its correlation with matrix metalloproteinase 2.
AB  - OBJECTIVE: To investigate the involvement of the anticoagulant serine protease
      activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA).
      METHODS: PC/APC, matrix metalloproteinase 2 (MMP-2), and MMP-9 were detected in
      synovial fluid by Western blotting, and their antigen levels were quantified by
      enzyme-linked immunosorbent assay in patients with osteoarthritis (OA) or RA.
      Enzymatic activity of MMP-2 was assayed using a specific fluorogenic substrate.
      We developed an improved assay to measure APC activity in synovial fluid
      utilizing a chromogenic substrate following immunoprecipitation with a specific
      PC/APC antibody. PC/APC and MMP-2 were localized by immunohistochemistry in RA,
      OA, and normal synovial tissues. RESULTS: Synovial fluid analysis demonstrated
      that APC is present in both RA and OA synovial fluid, with APC activity being
      markedly higher in RA (mean +/- SEM 462 +/- 112 ng/ml versus 136 +/- 42 ng/ml; P
      < 0.02). A correlation (r(2) = 0.61) was found between APC and MMP-2 activity
      levels in RA patients, but not in OA patients. Immunohistochemical studies of
      synovial sections showed colocalization of APC and MMP-2 in endothelial and
      synovial lining cells. Additionally, APC and MMP-2 coimmunoprecipitated with an
      anti-PC/APC antibody. CONCLUSION: Our results show, for the first time, that APC
      and MMP-2 are coordinately up-regulated and tightly bound in RA synovial fluid
      and colocalized in synovia. Their association suggests that APC may modulate MMP
      2 activity in RA.

PMID- 15248211
TI  - Lymphotoxin beta-mediated stimulation of synoviocytes in rheumatoid arthritis.
AB  - OBJECTIVE: Lymphotoxin beta (LTbeta), a cytokine produced by T cells and B cells,
      plays a central role in the normal development of lymph nodes and is critical in
      the formation of ectopic germinal center reactions in rheumatoid synovitis.
      Because resident fibroblast-like synoviocytes (FLS) express receptors for LTbeta,
      we examined the consequences of FLS activation by LTbeta. METHODS: FLS from
      patients with rheumatoid arthritis were isolated and examined for the expression
      of LTbeta receptor. FLS were incubated with LTalpha1beta2 and assayed for the
      production of cytokines and chemokines and the up-regulation of adhesion
      molecules. RESULTS: Exposure of FLS to recombinant LTalpha1beta2 resulted in the
      production of multiple inflammatory cytokines and metalloproteinases, implicating
      FLS as amplifiers of the inflammatory process in the inflamed joint.
      Additionally, LTalpha1beta2 was found to up-regulate the expression of cell
      adhesion molecules, rendering FLS to efficient adhesion substrates for T cells.
      LTalpha1beta2 also induced production of the chemokines CCL2 and CCL5, which
      elicited transmigration activity of T cells. Upon stimulation with LTalpha1beta2,
      FLS did not acquire characteristics of follicular dendritic cells. CONCLUSION:
      These data document that FLS are involved in multiple stages of the inflammatory
      process, including the recruitment and retention of lymphocytes in the synovial
      microenvironment. We propose that the heterotypic interaction between LTbeta
      producing lymphocytes and responding FLS contributes to the establishment of
      complex lymphoid microstructures, and that this may be one element that defines
      susceptibility of the synovial membrane to lymphoid organogenesis.

PMID- 15248213
TI  - Endothelial precursor cells in the synovial tissue of patients with rheumatoid
      arthritis and osteoarthritis.
AB  - OBJECTIVE: To find evidence for the presence of endothelial precursor cells,
      which can induce new vessel formation, in the synovial tissue of patients with
      rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Precursor cells in
      the synovial tissue of 18 RA patients and 15 OA patients were identified by
      immunohistochemistry, morphometric analysis, and confocal laser scanning
      microscopy using the following phenotype markers: CD31, CD34, STRO-1, CD133,
      vascular endothelial growth factor receptor 2 (VEGFR-2), and CXCR4. The presence
      of CD31, CD34, CD133, VEGFR-2, and CXCR4 messenger RNA in the synovial tissue was
      determined by reverse transcriptase-polymerase chain reaction, and the message
      for CXCR4 was quantified by an RNase protection assay. RESULTS: A population of
      cells that expressed CD34 on their surface but lacked the endothelial cell marker
      CD31 was found in the synovial tissue of RA and OA patients. CD34+,CD31- cells
      were detected in close proximity to STRO-1+ and CD133+ cells, forming cell
      clusters in the sublining area of the synovial membrane. Within these cell
      clusters, CD34+,CD31- precursor cells were located on the inside surrounded by
      STRO-1+ cells and with CD133+ cells on the outside. CD34+ precursor cells in the
      cell layer expressed high levels of the chemokine receptor CXCR4, while VEGFR-2
      was expressed on CD34+ and CD133+ cells, and alpha-smooth muscle actin was
      expressed on STRO-1+ cells. CONCLUSION: The presence of endothelial precursor
      cells in the synovial tissue of RA and OA patients provides evidence for
      vasculogenesis induced by precursor cells that arise in situ or from circulating
      progenitors.

PMID- 15248214
TI  - Amplification of the synovial inflammatory response through activation of mitogen
      activated protein kinases and nuclear factor kappaB using ligation of CD40 on
      CD14+ synovial cells from patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the signal transduction pathways in CD14+ synovial cells
      from patients with rheumatoid arthritis (RA) after CD40 ligation, and to examine
      their role in amplifying synovial inflammation in affected joints. METHODS:
      Expression of messenger RNA was analyzed using quantitative reverse transcription
      polymerase chain reaction. Cytokines and chemokines were measured using enzyme
      linked immunosorbent assay. Activation of kinases was detected using Western
      blotting. Nuclear translocation of NF-kappaB was examined using
      immunohistochemistry. CD14+ synovial cells were enriched using magnetic cell
      sorting. Fibroblast-like synoviocytes (FLS) were obtained by passaging primary
      synovial cell culture. RESULTS: Stimulation of CD14+ synovial cells from RA
      patients by recombinant soluble CD154 (rsCD154) significantly induced expression
      of tumor necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), and IL
      1beta. CD14+ RA synovial cells stimulated with rsCD154 plus interferon-gamma
      (IFNgamma) induced significantly higher production of IL-6, IL-8, and monocyte
      chemoattractant protein 1 by FLS compared with unstimulated CD14+ synovial cells,
      through TNFalpha-, IL-1alpha-, and IL-1beta-mediated pathways. Stimulation with
      rsCD154 plus IFNgamma induced the activation of ERK-1/2, p38 MAPK, and NF-kappaB.
      Specific inhibitors of MAPK/ERK-1/2 kinases and p38 MAPK significantly reduced
      the production of TNFalpha and IL-1beta by rsCD154 plus IFNgamma-stimulated CD14+
      synovial cells, and also inhibited production of these cytokines by freshly
      isolated synovial cells from RA patients. CONCLUSION: These data indicate that
      the CD40-CD154 interaction activates the ERK, p38, and NF-kappaB pathways in
      CD14+ synovial cells from RA patients to produce TNFalpha, IL-1alpha, and IL
      1beta, which in turn amplifies inflammatory responses by stimulating FLS.
      Inhibition of the CD40-CD154 interaction or its signal transduction pathways
      would be a strong and efficient strategy for the management of synovial
      inflammation in RA.

PMID- 15248215
TI  - Articular hypermobility is a protective factor for hand osteoarthritis.
AB  - OBJECTIVE: Very few studies have evaluated the association of articular
      hypermobility and radiographic osteoarthritis (OA) in humans. We assessed
      hypermobility and its relationship to radiographic hand OA in a family-based
      study. METHODS: A total of 1,043 individuals were enrolled in the multicenter
      Genetics of Generalized Osteoarthritis study, in which families were required to
      have 2 siblings with radiographic OA involving >/=3 joints (distributed
      bilaterally) of the distal interphalangeal (DIP), proximal interphalangeal (PIP),
      or carpometacarpal (CMC) joint groups, and OA in at least one DIP joint.
      Radiographic OA was defined as a score of >/=2 on the Kellgren/Lawrence scale in
      one or more joints within the group. The Beighton criteria for assessment of
      hypermobility were recorded on a 0-9-point scale. Hypermobility was defined as a
      Beighton score of >/=4, a threshold generally used to establish a clinical
      diagnosis of joint laxity. A threshold of >/=2 was also evaluated to assess
      lesser degrees of hypermobility. The Beighton score for the present was
      calculated based on clinical examination, and that for the past was based on
      recall of childhood hypermobility in the first 2 decades of life. The association
      of hypermobility and radiographic OA of the PIP, CMC, and metacarpophalangeal
      joints was evaluated in all participants and in men and women separately.
      Multiple logistic regression was used to examine the relationship of
      hypermobility with radiographic OA in each joint group, after adjusting for age
      and sex. The association of hypermobility and DIP OA was not evaluated, because
      evidence of DIP OA was required for study inclusion. RESULTS: Using a threshold
      Beighton score of 4, 3.7% of individuals were classified as hypermobile based on
      the present examination, and 7.4% were classified as hypermobile based on the
      past assessment. A significant negative association between present hypermobility
      and age was observed. In persons with hypermobility, the odds of OA in PIP joints
      was lower (for present, odds ratio [OR] 0.34, 95% confidence interval [95% CI]
      0.16-0.71; for past, OR 0.43, 95% CI 0.24-0.78). Similar results were obtained
      using a threshold Beighton score of 2. The lower odds of PIP OA with
      hypermobility were significant after adjusting for sex and age (for present, OR
      0.44, 95% CI 0.20-0.94; for past, OR 0.48, 95% CI 0.26-0.87). CONCLUSION: This
      study demonstrated a joint-protective effect of hypermobility for radiographic OA
      of PIP joints. In contrast to previous studies showing an association of
      hypermobility and CMC OA, in this cohort there was no evidence for increased odds
      of OA in any joint group of the hand in association with articular hypermobility.

PMID- 15248216
TI  - Varus-valgus alignment in the progression of patellofemoral osteoarthritis.
AB  - OBJECTIVE: To test the hypotheses that lateral patellofemoral (PF) osteoarthritis
      (OA) progression is more common than medial PF OA progression, that varus
      alignment increases the likelihood of medial PF OA progression, and that valgus
      alignment increases the likelihood of lateral PF OA progression. METHODS:
      Patients with knee OA were recruited from the community. Inclusion criteria were
      definite osteophyte presence (i.e., Kellgren/Lawrence radiographic grade >/=2) in
      1 or both knees and at least some difficulty with knee-requiring activity. Varus
      valgus alignment (the angle formed by the intersection of the mechanical axes of
      the femur and tibia) was measured on a full-limb radiograph at baseline. To
      assess PF OA progression, weight-bearing skyline views of the PF compartment were
      obtained at baseline and at 18-month followup. Knees with the highest grade of PF
      narrowing at baseline were excluded from analysis. Logistic regression and
      generalized estimating equations were used; odds ratios (ORs) were adjusted for
      age, sex, and body mass index. RESULTS: Lateral PF OA progression, which occurred
      in 120 (30%) of 397 knees, was more common than was medial PF OA progression,
      which occurred in 60 knees (15%). Varus (versus nonvarus) alignment increased the
      odds of PF OA progression isolated to the medial PF compartment (adjusted OR
      1.85, 95% confidence interval [95% CI] 1.00-3.44). Valgus alignment increased the
      odds of PF OA progression isolated to the lateral compartment (adjusted OR 1.64,
      95% CI 1.01-2.66). CONCLUSION: Lateral PF OA progression was more common than
      medial progression, and varus-valgus alignment influenced the likelihood of PF OA
      progression in a compartment-specific manner. Interventions that address the
      stress imposed by alignment on the PF compartments may delay PF OA progression
      and should be developed.

PMID- 15248217
TI  - A randomized trial of parenteral methotrexate comparing an intermediate dose with
      a higher dose in children with juvenile idiopathic arthritis who failed to
      respond to standard doses of methotrexate.
AB  - OBJECTIVE: To compare the safety and efficacy of parenteral methotrexate (MTX) at
      an intermediate dosage (15 mg/m(2)/week) versus a higher dosage (30 mg/m(2)/week)
      in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who
      failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/week).
      METHODS: In the screening phase, 595 patients who were newly started on a
      standard dose of MTX were followed up for 6 months. Subsequently, the
      nonresponders, defined according to the American College of Rheumatology (ACR)
      pediatric 30% improvement criteria (pediatric 30), were randomized to receive an
      intermediate dose or higher dose of parenteral MTX for an additional 6 months.
      Improvement in the screening and randomization phase was defined by the ACR
      pediatric 30 response, as well as by the 50% and 70% response levels (ACR
      pediatric 50 and ACR pediatric 70, respectively). RESULTS: In the screening
      phase, after receiving standard doses of MTX, 430 patients (72%) improved
      according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and
      225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the
      definition of complete disease control. Of the 133 nonresponders, 80 were
      randomized to receive an intermediate dose or higher dose of MTX. In the
      randomization phase, the ACR pediatric 30 response rate was 25 of 40 children
      (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the
      higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients
      (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group.
      An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an
      intermediate dose versus 19 (47.5%) receiving a higher dose. Five children
      (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose
      of MTX also met the definition of complete disease control. None of the
      intergroup differences in response rate were significant. There were no
      significant differences in the frequency of adverse events or laboratory
      abnormalities between the 2 randomized groups. CONCLUSION: This study shows that
      the plateau of efficacy of MTX in JIA is reached with parenteral administration
      of 15 mg/m(2)/week and that a further increase in dosage is not associated with
      any additional therapeutic benefit. MTX should be administered for up to 9-12
      months to appreciate its full therapeutic effect.

PMID- 15248218
TI  - Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response
      to pulse cyclophosphamide in lupus nephritis.
AB  - OBJECTIVE: Pulse cyclophosphamide is the treatment of choice for severe lupus
      nephritis. However, not all patients respond to this therapy, and gonadal
      toxicity is of particular concern. Cyclophosphamide is a prodrug that requires
      activation by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort
      study to test whether genetic polymorphisms of these enzymes are associated with
      the toxicity of, and clinical response to, cyclophosphamide in patients with
      lupus nephritis. METHODS: Sixty-two patients with proliferative lupus nephritis
      treated with cyclophosphamide were genotyped for common variant alleles of
      CYP2B6, 2C19, 2C9, and 3A5. We examined the association between these genotypes
      and the following clinical end points: development of premature ovarian failure,
      end-stage renal disease (ESRD), doubling of serum creatinine level, and
      achievement of complete renal response. RESULTS: The observed frequencies of the
      variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%,
      4.0%, and 75.8%, respectively. Patients who were either heterozygous or
      homozygous for CYP2C19*2 had a significantly lower risk of developing premature
      ovarian failure (relative risk 0.10; 95% confidence interval 0.02-0.52), after
      adjustment for age and total number of cyclophosphamide pulses received. In a
      survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4)
      had a higher probability of reaching ESRD (P = 0.0005) and of doubling the
      creatinine level (P = 0.0005) as well as a trend toward a lower probability of
      achieving a complete renal response (P = 0.051). CONCLUSION: Determination of
      selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk
      of premature ovarian failure in lupus nephritis patients treated with
      cyclophosphamide. The association of these genotypes with renal response needs
      further validation.

PMID- 15248220
TI  - Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2
      autoantigen from connective tissue disease patients assist in autoantibody
      production.
AB  - OBJECTIVE: To identify and characterize human T cells reactive with heterogeneous
      nuclear RNP A2 (hnRNP A2) antigen, and to determine the ability of hnRNP-reactive
      T cells to assist in the production of human autoantibodies. METHODS: T cells
      from patients with high serum levels of anti-hnRNP IgG autoantibody were
      stimulated with an hnRNP recombinant fusion protein, and the cells were cloned by
      limiting dilution. The surface phenotype and cytokine profiles of the T cells
      were examined by flow cytometry and enzyme-linked immunosorbent assay (ELISA),
      respectively. T cell clones were cultured with highly purified autologous B
      cells, and the ability of T cells to enhance autoantibody production under a
      variety of conditions was measured by ELISA. RESULTS: Human T cells reactive with
      hnRNP antigen were cloned from 2 patients with systemic lupus erythematosus (SLE)
      and 1 patient with mixed connective tissue disease (MCTD). The T cells were CD4+
      and had a Th1-like functional phenotype. In coculture in vitro with autologous B
      cells, T cell clones augmented anti-hnRNP autoantibody production and did so
      without the need for direct T cell-B cell contact. CONCLUSION: This study
      provides direct evidence for a role of anti-hnRNP-reactive T cells in
      autoantibody production in SLE and MCTD. These findings support the notion that
      hnRNP-reactive T cells play a role in the pathogenesis of these diseases.

PMID- 15248219
TI  - Association of the CT60 marker of the CTLA4 gene with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the possible association of the CT60A/G marker with
      systemic lupus erythematosus (SLE) in Spanish patients, and to identify the
      possible CTLA4 haplotype responsible for the association, taking into account
      other polymorphisms described at positions -1722T/C, -319C/T, +49A/G, and the
      microsatellite (AT)(n) in the 3'-untranslated region (3'-UTR) of the CTLA4 gene.
      METHODS: Genotyping of CT60 was performed in 395 patients with SLE and 293
      healthy controls using polymerase chain reaction (PCR)-restriction fragment
      length polymorphism analysis. Genotyping of the rest of the dimorphisms has been
      previously reported. Genotyping of microsatellite polymorphism (AT)(n) in the 3'
      UTR was performed using PCR with a fluorescence-labeled primer. RESULTS: With
      regard to CT60A/G, the frequency of the AA genotype was significantly decreased
      among the SLE patients (18.7% versus 28.3% in the control group; P = 0.003,
      corrected P [P(corr)] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval
      [95% CI] 0.40-0.85). In other words, the frequency of individuals bearing the G
      phenotype was increased in the patient group compared with the control group
      (81.2% versus 71.7%; P = 0.003, P(corr) = 0.006, OR = 1.71, 95% CI 1.18-2.49).
      The distribution of allele frequency was also significantly different between
      patients and controls (P = 0.01, P(corr) = 0.02, OR [for allele G] = 1.32, 95% CI
      1.06-1.65). After combining the data on the different polymorphisms, 2 neutral
      haplotypes were found: +49A;(AT)(7);CT60A and +49G;(AT)(8-19);CT60G. In addition,
      a susceptibility haplotype was found: +49A;(AT)(>19);CT60G. CONCLUSION: The 3'
      UTR of the CTLA4 gene is involved in susceptibility to SLE.

PMID- 15248221
TI  - First-degree heart block in the fetus of an anti-SSA/Ro-positive mother: reversal
      after a short course of dexamethasone treatment.
AB  - Isolated congenital heart block is almost invariably associated with the presence
      of antibodies to SSA/Ro and SSB/La antigens in the maternal circulation. Once
      established, third-degree congenital heart block is permanent. However, a lesser
      degree of autoantibody-associated heart block in a fetus can be reversed if it is
      recognized and treated early enough with fluorinated glucocorticosteroids. The
      only method available clinically for the recognition of first-degree heart block
      in a fetus is measurement of the mechanical PR interval by pulsed Doppler
      echocardiography. This is the first report of a fetus in whom a diagnosis of
      first-degree heart block and the consequent decision to intervene were based
      solely on this technique. In addition, the first-degree heart block resolved
      completely after only 2 weeks of dexamethasone treatment, and the heart rhythm
      remained stable throughout the remainder of the pregnancy despite early
      discontinuation of therapy due to oligohydramnios.

PMID- 15248222
TI  - Dichotomous effects of complete versus partial class II major histocompatibility
      complex deficiency on circulating autoantibody levels in autoimmune-prone mice.
AB  - OBJECTIVE: To assess the effects of altered class II major histocompatibility
      complex (MHCII) expression on circulating autoantibody levels in C57BL/6 (B6)
      mice congenic for the Sle1 (B6.Sle1 mice) or Nba2 (B6.Nba2 mice) regions.
      METHODS: H-2Ab(+/+) (MHCII-intact), H-2Ab(+/-) (MHCII-intermediate), and H-2Ab(-/
      ) (MHCII-deficient) littermate B6.Sle1 and B6.Nba2 mice were evaluated for spleen
      cell phenotype, numbers of splenic Ig-secreting cells, and serum levels of total
      IgM, total IgG, IgG antichromatin, IgG antihistone, and IgG anti-double-stranded
      DNA (anti-dsDNA). RESULTS: Compared with their MHCII-intact littermates, MHCII
      deficient B6.Sle1 and B6.Nba2 mice developed markedly decreased circulating
      levels of IgG autoantibodies, along with decreased circulating levels of total
      IgG. In sharp contrast, MHCII-intermediate mice developed increased circulating
      levels of IgG autoantibodies. This was associated with increased numbers of
      splenic Ig-secreting cells and serum levels of total IgG in B6.Sle1 mice, but it
      occurred without concomitant increases in the numbers of splenic Ig-secreting
      cells or serum total IgG levels in B6.Nba2 mice. CONCLUSION: In 2 clinically
      healthy strains of mice with a genetic proclivity for developing autoantibodies,
      the effects of class II MHC expression on levels of circulating IgG
      autoantibodies were found to be complex. In the absence of MHCII expression,
      circulating IgG autoantibody levels were minimal. With full MHCII expression,
      circulating IgG autoantibody levels were considerable. With intermediate MHCII
      expression, circulating IgG autoantibody levels were even greater. These last
      findings may help explain why heterozygosity at the H-2 locus is associated with
      increased autoantibody titers and aggravated disease in certain lupus-prone mice.

PMID- 15248223
TI  - Etanercept in Sjogren's syndrome: a twelve-week randomized, double-blind, placebo
      controlled pilot clinical trial.
AB  - OBJECTIVE: To assess the safety and potential efficacy of etanercept in the
      treatment of Sjogren's syndrome (SS). METHODS: This pilot study was a 12-week
      randomized, double-blind, placebo-controlled trial of etanercept, with 14
      subjects in each group. Patients received 25 mg of etanercept or placebo
      (vehicle) by twice-weekly subcutaneous injection. Patients met the American
      European Consensus Group criteria for SS. The primary outcome required at least
      20% improvement from baseline values for at least 2 of the following 3 domains:
      subjective or objective measures of dry mouth, subjective or objective measures
      of dry eyes, and IgG level or erythrocyte sedimentation rate (ESR). RESULTS: Of
      the 14 patients taking etanercept, 11 had primary SS and 3 had SS secondary to
      rheumatoid arthritis. Baseline measures did not differ between the 2 groups.
      Three etanercept-treated patients and 1 placebo-treated patient did not complete
      the trial. Five etanercept-treated patients and 3 placebo-treated patients showed
      improvement from baseline in the primary outcome variable at 12 weeks, but the
      difference was not statistically significant. There were no significant
      differences between the groups for changes in subjective measures of oral or
      ocular symptoms (by visual analog scale), the IgG level, Schirmer I test result,
      van Bijsterveld score, or salivary flow. At 12 weeks, the ESR had decreased in
      the etanercept group compared with baseline (P = 0.004); however, the mean
      reduction was only 18.6%. CONCLUSION: We found no evidence to suggest that
      treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was
      clinically efficacious in SS. A larger trial will be necessary to definitively
      address the efficacy of etanercept in the treatment of SS.

PMID- 15248224
TI  - Genetic studies in familial ankylosing spondylitis susceptibility.
AB  - OBJECTIVE: To define the genetic basis of susceptibility to ankylosing
      spondylitis (AS), especially non-major histocompatibility complex (MHC) genes.
      METHODS: The study group comprised 244 affected sibling pairs from 180 pedigrees
      of primarily European ancestry. Sibling pairs were concordant for AS by the
      modified New York criteria and had available sacroiliac radiographs. The subjects
      were genotyped for 400 markers in ABI PRISM linkage map MD-10 and for 17
      additional markers on chromosomes 6p, 6q, and 11q (including HLA-B, DRB1, DQA1,
      DQB1, and DPB1 alleles). Two-point and multipoint nonparametric linkage (NPL)
      analyses were conducted using the NPL statistic and 1-parameter allele-sharing
      model logarithm of odds (LOD) scores, calculated using the Allele-Sharing Model
      (ASM) computer program. RESULTS: Linkage of the MHC region was supported by both
      2-point and multipoint analyses, with the strongest peak (45.90 cM) in the MHC at
      the HLA-DRB1 locus (NPL score 8.720, ASM LOD score 20.49; P = 6.8 x 10(-20) for 2
      point analysis). A second region was found to have positive linkage at the q arm
      of chromosome 6 (D6S441) in 2-point analysis; this was supported by a 39.13-cM
      region (135.58-174.71 cM) in multipoint analysis, with the smallest P value (4.2
      x 10(-3)) at 166.39 cM. A third region was found on chromosome 11q, with the
      strongest evidence for linkage for D11S4094 at 123 cM (NPL score 2.235, ASM LOD
      score 1.939) and, on transmission disequilibrium test analysis, D11S4090 at
      105.74 cM (P = 6.2 x 10(-5)). Linkage in this area was supported by multipoint
      analysis, spanning 22.19 cM continuously from 101.68 cM to 123.87 cM, with the
      strongest peak at 112.33 cM (P = 0.014); this was confirmed by subsequent fine
      mapping studies. CONCLUSION: Thus, this genome-wide scan implicates, in addition
      to the MHC, regions outside the MHC in AS susceptibility, especially on
      chromosomes 6q and 11q.

PMID- 15248225
TI  - Enhanced intracellular replication of Salmonella enteritidis in HLA-B27
      expressing human monocytic cells: dependency on glutamic acid at position 45 in
      the B pocket of HLA-B27.
AB  - OBJECTIVE: To reveal the cause of the impaired elimination of Salmonella
      enteritidis in HLA-B27-transfected human monocytic cells and to study whether the
      B pocket of HLA-B27 contributes to these modulatory effects. METHODS: Stable U937
      cell transfectants expressing HLA-A2, B27, or different forms of B27 with amino
      acid substitutions in the B pocket were prepared. Mock-transfected cells were
      prepared using the antibiotic resistance vector (pSV2neo) alone. Cells were
      differentiated, infected with S enteritidis, and the number of live intracellular
      S enteritidis organisms was determined using the colony-forming unit method. To
      visualize intracellular S enteritidis, the bacteria were transformed with green
      fluorescent protein (GFP), and studied by confocal microscopy. RESULTS: Cells
      expressing wild-type HLA-B27 were more permissive of intracellular replication of
      S enteritidis compared with mock-transfected or A2-transfected controls. Cells
      expressing B27 with an altered B pocket composition having either 6 amino acid
      substitutions (B27.A2B; substitutions H9F, T24A, E45M, I66K, C67V, and K70H) or a
      single substitution (B27.E45M) were no longer permissive of S enteritidis
      replication. In contrast, cells expressing B27 with the single substitution of F
      for H at position 9 (B27.H9F) retained their permissiveness. Studies using GFP
      transformed S enteritidis confirmed that the increase in the amount of
      intracellular bacteria in B27-expressing cells was due to replication of the
      bacteria. CONCLUSION: Our data indicate that HLA-B27 expression modulates the
      host-microbe interaction that results in an impaired capacity of monocytes to
      resist intracellular replication of S enteritidis. The phenotype is dependent on
      glutamic acid at position 45 in the B pocket and, thus, may be due to properties
      of the B27 heavy chain that are related to this residue. The ability of HLA-B27
      to confer susceptibility to Salmonella-triggered reactive arthritis may occur, at
      least in part, through these modulatory effects.

PMID- 15248226
TI  - Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on
      disease progression.
AB  - OBJECTIVE: Etanercept has been shown to improve the articular and cutaneous
      manifestations of psoriatic arthritis (PsA). In this study, we further evaluated
      the safety, efficacy, and effect on radiographic progression of etanercept in
      patients with PsA. METHODS: Patients with PsA (n = 205) were randomized to
      receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks.
      Patients continued to receive blind-labeled therapy in a maintenance phase until
      all had completed the 24-week phase, then could receive open-label etanercept in
      a 48-week extension. Efficacy and safety were evaluated at 4, 12, and 24 weeks
      and at 12-week intervals thereafter. Radiographs of the hands and wrists were
      assessed at baseline and 24 weeks, at entry to the open-label phase, and after 48
      weeks in the study. RESULTS: Etanercept significantly reduced the signs and
      symptoms of PsA and psoriasis. At 12 weeks, 59% of etanercept patients met the
      American College of Rheumatology 20% improvement criteria for joint response,
      compared with 15% of placebo patients (P < 0.0001), and results were sustained at
      24 and 48 weeks. At 24 weeks, 23% of etanercept patients eligible for psoriasis
      evaluation achieved at least 75% improvement in the Psoriasis Area and Severity
      Index, compared with 3% of placebo patients (P = 0.001). Radiographic disease
      progression was inhibited in the etanercept group at 12 months; the mean
      annualized rate of change in the modified total Sharp score was -0.03 unit,
      compared with +1.00 unit in the placebo group (P = 0.0001). Etanercept was well
      tolerated. CONCLUSION: Etanercept reduced joint symptoms, improved psoriatic
      lesions, inhibited radiographic progression, and was well tolerated in patients
      with PsA.

PMID- 15248227
TI  - Macrophage release of transforming growth factor beta1 during resolution of
      monosodium urate monohydrate crystal-induced inflammation.
AB  - OBJECTIVE: It has previously been shown that as monocytes differentiate into
      macrophages, they lose the ability to secrete proinflammatory cytokines in
      response to monosodium urate monohydrate (MSU) crystals. The purpose of this
      study was to investigate whether MSU crystals induce macrophages to secrete
      antiinflammatory factor instead. METHODS: Human monocyte or macrophage isolates
      were prepared from samples obtained from healthy volunteer donors either by
      differentiation of blood monocytes in vitro or by collecting cells from skin
      blisters during the early or late phase of the dermal inflammatory response to
      cantharidin. Monocyte or macrophage isolates were then incubated with MSU
      crystals for 24 hours, and culture supernatants were assayed for candidate
      antiinflammatory mediators (by enzyme-linked immunosorbent assay) and for the
      capacity to activate or suppress endothelial cell E-selectin expression and
      secondary neutrophil recruitment under shear flow. RESULTS: Analysis of
      supernatants from in vitro-differentiated macrophages revealed that transforming
      growth factor beta1 (TGFbeta1) was induced following MSU crystal stimulation
      (mean +/- SEM 1.50 +/- 0.24 ng/ml/10(6) cells), but there was no evidence of
      interleukin-10 (IL-10), IL-1 receptor antagonist, or tumor necrosis factor (TNF)
      receptor p55 release. Macrophage TGFbeta1 significantly suppressed endothelial
      cell E-selectin expression and secondary neutrophil capture on endothelial
      monolayers stimulated with supernatants from MSU-treated monocytes. Leukocytes
      isolated from resolving (40-hour) skin blisters similarly elaborated TGFbeta1
      when challenged with MSU crystals (0.66 +/- 1.3 ng/ml/10(5) CD14+ cells). In
      contrast, cells isolated from acute (16-hour) skin blisters secreted TNFalpha
      (0.49 +/- 0.08 ng/ml/10(5) CD14+ cells) but no detectable TGFbeta1. CONCLUSION:
      These data provide further support for the concept that differentiated
      macrophages play a protective role in the pathophysiology of gout, and they
      identify macrophage TGFbeta1 as a mediator of paracrine suppression during the
      resolution phase of inflammation.

PMID- 15248228
TI  - International consensus on preliminary definitions of improvement in adult and
      juvenile myositis.
AB  - OBJECTIVE: To use a core set of outcome measures to develop preliminary
      definitions of improvement for adult and juvenile myositis as composite end
      points for therapeutic trials. METHODS: Twenty-nine experts in the assessment of
      myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles
      as clinically improved or not improved. Two hundred twenty-seven candidate
      definitions of improvement were developed using the experts' consensus ratings as
      a gold standard and their judgment of clinically meaningful change in the core
      set of measures. Seventeen additional candidate definitions of improvement were
      developed from classification and regression tree analysis, a data-mining
      decision tree tool analysis. Six candidate definitions specifying percentage
      change or raw change in the core set of measures were developed using logistic
      regression analysis. Adult and pediatric working groups ranked the 13 top
      performing candidate definitions for face validity, clinical sensibility, and
      ease of use, in which the sensitivity and specificity were >/=75% in adult,
      pediatric, and combined data sets. Nominal group technique was used to facilitate
      consensus formation. RESULTS: The definition of improvement (common to the adult
      and pediatric working groups) that ranked highest was 3 of any 6 of the core set
      measures improved by >/=20%, with no more than 2 worse by >/=25% (which could not
      include manual muscle testing to assess strength). Five and 4 additional
      preliminary definitions of improvement for adult and juvenile myositis,
      respectively, were also developed, with several definitions common to both
      groups. Participants also agreed to prospectively test 6 logistic regression
      definitions of improvement in clinical trials. CONCLUSION: Consensus preliminary
      definitions of improvement were developed for adult and juvenile myositis, and
      these incorporate clinically meaningful change in all myositis core set measures
      in a composite end point. These definitions require prospective validation, but
      they are now proposed for use as end points in all myositis trials.

PMID- 15248229
TI  - Involvement of chemokines and Th1 cytokines in the pathogenesis of mucocutaneous
      lesions of Behcet's disease.
AB  - OBJECTIVE: To investigate a possible pathogenic role of cytokines in Behcet's
      disease (BD) by focusing on the analysis of cytokine gene expression within
      mucocutaneous BD lesions. METHODS: The study group comprised 20 patients with
      active BD. In this group, a set of chemokines as well as Th1 and Th2 cytokines in
      biopsy specimens obtained from oral and genital ulcers, pseudofolliculitis
      lesions, and lesions at the site of pathergy testing were studied using real-time
      quantitative reverse transcriptase-polymerase chain reaction. RESULTS: We
      observed important increases in the expression of interleukin-8 (IL-8) (
      approximately 700-fold), monocyte chemoattractant protein 1 ( approximately 65
      fold), interferon-gamma ( approximately 71-fold), and IL-12 ( approximately 69
      fold) messenger RNA in BD lesions compared with normal skin. Except for IL-10 (
      approximately 75-fold increase), Th2 cytokines (i.e., IL-4 and IL-13) were
      absent. CONCLUSION: Our data suggest a direct role of Th1 lymphocytes in the
      pathogenesis of mucocutaneous BD lesions.

PMID- 15248230
TI  - Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu
      arteritis.
AB  - OBJECTIVE: Granulomatous inflammation is a typical feature of Takayasu arteritis
      (TA), and tumor necrosis factor (TNF) is important in the formation of
      granulomas. In this study, we assessed therapy with anti-TNF agents in patients
      with TA that was not controlled by glucocorticoid therapy or other
      immunosuppressants. METHODS: We conducted an open-label trial of anti-TNF therapy
      at 3 academic medical centers over a period of 4.25 years. Fifteen patients with
      active, relapsing TA (median 6 years) were selected. Seven received etanercept
      (later changed to infliximab in 3 patients), and 8 received infliximab. Relapses
      had occurred in all patients while they were receiving glucocorticoids and, in 13
      patients, additional immunosuppressive drugs. No other agents were added to the
      treatment regimen concurrently with anti-TNF. If patients were receiving
      cytotoxic agents, the dosage was not increased. Clinical symptoms were recorded,
      and physical examinations, laboratory studies, and serial magnetic resonance
      imaging were performed. RESULTS: The median daily dose of prednisone required to
      maintain remission prior to anti-TNF therapy was 20 mg. Ten of the 15 patients
      achieved complete remission that was sustained for 1-3.3 years without
      glucocorticoid therapy. Four patients achieved partial remission, with a >50%
      reduction in the glucocorticoid requirement. At a median of 12 months of
      followup, the median dose of prednisone was 0. Therapy failed in 1 patient. In 9
      of the 14 responders, an increase in the anti-TNF dosage was required to sustain
      remission. Two relapses occurred during periods when anti-TNF therapy
      (etanercept) was interrupted, but remission was reestablished upon reinstitution
      of therapy. CONCLUSION: In this pilot study of relapsing TA, addition of anti-TNF
      therapy resulted in improvement in 14 of 15 patients and sustained remission in
      10 of 15 patients, who were able to discontinue glucocorticoid therapy. Anti-TNF
      may be a useful adjunct to glucocorticoids in the treatment of TA. Our results
      justify a randomized, controlled clinical trial of anti-TNF therapy for TA.

PMID- 15248231
TI  - Absence of antibodies to cyclic citrullinated peptide in sera of patients with
      hepatitis C virus infection and cryoglobulinemia.
AB  - OBJECTIVE: To determine if antibodies to cyclic citrullinated peptide (anti-CCP)
      are found in chronic hepatitis C virus (HCV) infection. METHODS: Rheumatoid
      factor (RF) and anti-CCP were measured in sera from 50 patients with HCV
      infection but without cryoglobulinemia, sera from 29 patients with mixed
      cryoglobulinemia (including 13 with rheumatic symptoms and 5 with arthritis), and
      sera from 20 normal blood donors. Anti-CCP was measured by second-generation
      enzyme-linked immunosorbent assay (ELISA). RESULTS: No sera with elevated anti
      CCP were found in patients with HCV infection without cryoglobulinemia, and in
      that population, the maximum anti-CCP was 10 units, well below the positive
      cutoff of 20 units. Positive findings on RF testing >13 IU/ml were present in 22
      (44%) of the HCV patients, with RF >50 IU/ml in 8 (16%) and a maximum RF of 526
      IU/ml. Of the cryoglobulinemia patients, 22 (76%) had positive results on tests
      for RF, including 18 (62%) with RF >50 IU/ml and a maximum RF of 5,540 IU/ml. Two
      (6.9%) of the cryoglobulinemia patients had borderline-positive findings on tests
      for anti-CCP (25 units and 37 units), which were false-positive results caused by
      nonspecific binding in the ELISA. No association between the RF and the anti-CCP
      concentrations was found. CONCLUSION: Whereas RF was frequent in patients with
      HCV infection with and without cryoglobulinemia, anti-CCP was not observed in
      patients with uncomplicated HCV infection. Borderline-positive anti-CCP results
      were observed infrequently in patients with mixed cryoglobulinemia and were
      caused by nonspecific binding to plastic. Measurement of anti-CCP may help in
      diagnosing RA in patients with chronic HCV infection.

PMID- 15248232
TI  - Expression and function of RANK in human monocyte chemotaxis.
AB  - OBJECTIVE: RANKL, a member of the tumor necrosis factor superfamily, is a central
      regulator of osteoclast recruitment and activation. Whether RANKL affects
      monocyte locomotion in vitro via RANK and a possible signaling pathway were
      investigated. METHODS: Monocytes were obtained from venous blood of healthy
      donors. Cell migration was studied by micropore filter assays. The signaling
      mechanisms required for RANKL-dependent migration were tested using signaling
      enzyme blockers and Western blot analyses. Expression of RANK messenger RNA
      (mRNA) in monocytes was demonstrated by reverse transcriptase-polymerase chain
      reaction, and receptor expression on cell surface was investigated by
      fluorescence-activated cell sorting analyses. RESULTS: RANKL significantly
      stimulated monocyte chemotaxis via activation of phosphatidylinositol 3-kinase,
      phosphodiesterase, and Src kinase. The effect on migration was inhibited by
      osteoprotegerin, which is the decoy receptor for RANKL. Expression of RANK
      receptor mRNA was shown, and synthesis of RANK in monocytes was suggested by the
      detection of RANK immunoreactivity on the cell surface. CONCLUSION: These data
      suggest that RANK is expressed by monocytes whose activation by RANKL stimulates
      directed migration involving phosphatidylinositol 3-kinase, phosphodiesterase,
      and Src kinases.

PMID- 15248233
TI  - Medical care expenditures and earnings losses of persons with arthritis and other
      rheumatic conditions in the United States in 1997: total and incremental
      estimates.
AB  - OBJECTIVE: To provide estimates of the total medical care expenditures and
      earnings losses associated with arthritis and other rheumatic conditions (AORC),
      as well as the increment in such costs specifically attributable to these
      conditions, in the US in 1997. METHODS: The estimates were derived from the 1997
      Medical Expenditures Panel Survey (MEPS), a national probability sample of 14,147
      households including 34,551 persons, of whom 4,776 self-reported arthritis. After
      weighting, those who self-reported AORC represent 38.4 million persons. We
      tabulated all medical care expenditures of the adult MEPS respondents, stratified
      by arthritis and comorbidity status, and then used regression techniques to
      estimate the increment in health care expenditures attributable to AORC, after
      taking comorbidity, demographic characteristics, and insurance status into
      account. Using the same methods, we also estimated the magnitude of the earnings
      losses sustained by persons of working ages (18-64 years) who had AORC. RESULTS:
      Persons with AORC incurred mean total medical care expenditures of 4,865 dollars
      (total 186.9 billion dollars). The largest components of these expenditures were
      inpatient care (39%), ambulatory care (29%), and prescriptions (14%). The mean
      increment in medical care expenditures specifically attributable to AORC among
      those ages 18 years and older was 1,391 dollars(total approximately 51.1 billion
      dollars). Persons with AORC ages 18-64 years earned 3,812 dollars less on average
      than did other persons of these ages (total 82.4 billion dollars). Of this
      average, 1,579 dollars was attributable to the AORC (total 35.1 billion dollars).
      CONCLUSION: In 1997, persons with AORC incurred direct and indirect costs of
      269.3 billion dollars, of which 86.2 billion dollars was attributable to these
      conditions.

PMID- 15248234
TI  - Zoledronic acid protects against local and systemic bone loss in tumor necrosis
      factor-mediated arthritis.
AB  - OBJECTIVE: Increased osteoclast activity is a key factor in bone loss in
      rheumatoid arthritis (RA). This suggests that osteoclast-targeted therapies could
      effectively prevent skeletal damage in patients with RA. Zoledronic acid (ZA) is
      one of the most potent agents for blocking osteoclast function. We therefore
      investigated whether ZA can inhibit the bone loss associated with chronic
      inflammatory conditions. METHODS: Human tumor necrosis factor (TNF)-transgenic
      (hTNFtg) mice, which develop severe destructive arthritis as well as
      osteoporosis, were treated with phosphate buffered saline, single or repeated
      doses of ZA, calcitonin, or anti-TNF, at the onset of arthritis. RESULTS:
      Synovial inflammation was not affected by ZA. In contrast, bone erosion was
      retarded by a single dose of ZA (-60%) and was almost completely blocked by
      repeated administration of ZA (-95%). Cartilage damage was partly inhibited, and
      synovial osteoclast counts were significantly reduced with ZA treatment. Systemic
      bone mass dramatically increased in hTNFtg mice after administration of ZA, which
      was attributable to an increase in trabecular number and connectivity. In
      addition, bone resorption parameters were significantly lowered after
      administration of ZA. Calcitonin had no effect on synovial inflammation, bone
      erosion, cartilage damage, or systemic bone mass. Anti-TNF entirely blocked
      synovial inflammation, bone erosion, synovial osteoclast formation, and cartilage
      damage but had only minor effects on systemic bone mass. CONCLUSION: ZA appears
      to be an effective tool for protecting bone from arthritic damage. In addition to
      their role in antiinflammatory drug therapy, modern bisphosphonates are promising
      candidates for maintaining joint integrity and reversing systemic bone loss in
      patients with arthritis.

PMID- 15248235
TI  - Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen
      induced arthritis.
AB  - OBJECTIVE: To study the effect of zoledronic acid (ZA) on synovial inflammation,
      structural joint damage, and bone metabolism in rats during the effector phase of
      collagen-induced arthritis (CIA). METHODS: CIA was induced in female dark agouti
      rats. At the clinical onset of CIA, rats were assigned to treatment with vehicle
      or single subcutaneous doses of ZA (1.0, 10, 50, or 100 microg/kg). Clinical
      signs in all 4 paws were scored on a daily basis. After 2 weeks, the joints in
      the hind paws were assessed using plain radiographs, microfocal computed
      tomography (micro-CT), histologic scoring, and histomorphometry, and the serum
      levels of type I collagen crosslinks were measured by enzyme-linked immunosorbent
      assay. RESULTS: Although ZA mildly exacerbated synovitis, it effectively
      suppressed structural joint damage. At doses of >/=10 microg/kg, ZA significantly
      reduced radiographic bone erosions, Larsen scores, and juxtaarticular trabecular
      bone loss as quantified by micro-CT. ZA prevented increased type I collagen
      (bone) breakdown in CIA and diminished histologic scores of focal bone erosion by
      up to 80%. Increases in the percentage of eroded surface, osteoclast surface, and
      osteoclast numbers associated with CIA were prevented by ZA, even though
      synovitis scores were unchanged. CONCLUSION: Single doses (>/=10 microg/kg) of ZA
      strikingly reduced focal bone erosions and juxtaarticular trabecular bone loss,
      although synovitis was mildly exacerbated. Targeting osteoclasts with ZA may
      therefore be an effective strategy for preventing structural joint damage in
      rheumatoid arthritis.

PMID- 15248236
TI  - Antileukoproteinase: modulation of neutrophil function and therapeutic effects on
      anti-type II collagen antibody-induced arthritis.
AB  - OBJECTIVE: Antileukoproteinase (ALP) is a physiologic inhibitor of granulocytic
      serine proteases. The present study was undertaken to investigate its therapeutic
      benefit in an antibody-transfer model of erosive polyarthritis and to elucidate
      its potential to interfere with immune complex-dependent inflammatory pathways.
      METHODS: Arthritis development was induced in male (BALB/c x B10.Q)F(1) mice by
      intravenous injection of two monoclonal antibodies specific for type II collagen
      and was quantified by clinical scoring and histopathology. Arthritis severity was
      assessed in a cohort of mice under systemic treatment with recombinant human ALP
      (daily doses of 0.1 mg for 5 days starting immediately after disease induction)
      in comparison with untreated controls. Concomitantly, functional assays
      (phagocytosis, oxidative burst, fluorescence-activated cell sorting analysis of
      integrin expression) were performed on neutrophils upon in vitro stimulation by
      IgG-coated latex beads. RESULTS: ALP treatment reduced arthritis incidence and
      severity and had a protective effect against cartilage and bone erosion. ALP
      inhibited the conversion of the leukocyte beta2 integrins into an active
      conformation upon Fc receptor stimulation of granulocytes. ALP bound to the actin
      bundling protein L-plastin and down-modulated filamentous actin assembly in
      response to stimulation with IgG-coated latex beads in granulocytes. ALP exerted
      additional inhibitory effects on neutrophil functions associated with
      cytoskeletal reorganization, such as phagocytosis and oxidative burst.
      CONCLUSION: In addition to its antiprotease activity, ALP exerts a variety of
      blocking effects on neutrophil functions, probably due to modulation of
      cytoskeletal changes, that may contribute to this inhibitor's antiarthritis
      potential and qualify it as a multifunctional regulator of inflammatory
      responses.

PMID- 15248237
TI  - Outer surface lipoproteins of Borrelia burgdorferi vary in their ability to
      induce experimental joint injury.
AB  - OBJECTIVE: To examine the ability of bacterial lipoproteins from the spirochete
      Borrelia burgdorferi to cause in vivo tissue injury (arthritis). METHODS: Outer
      surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen
      induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB,
      and OspC in nonlipidated (peptide) and lipidated forms was performed in the left
      knee joint; the contralateral joint received buffer as control. Inflammation was
      monitored by technetium scintigraphy and histology. RESULTS: Nonlipidated
      (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was
      polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2
      different strains and lipidated OspC induced severe arthritis, whereas lipidated
      OspB failed to induce injury. A synthetic analog of the OSP lipid modification,
      lipopeptide Pam(3)Cys-Ser-Lys(4)-OH, either alone or coupled to bovine serum
      albumin, also failed to induce injury. Injury did not develop in control groups
      that were given the appropriate buffers or lipopolysaccharide. This showed that
      lipidated borrelial OSPs can be potent arthritogens but vary greatly with respect
      to their injury-inducing potential. The possession of a lipid modification is
      essential but is not sufficient to render an OSP arthritogenic. CONCLUSION: This
      is the first study to demonstrate that individual lipoproteins from B burgdorferi
      can induce experimental joint injury in vivo. These results may help elucidate
      the pathogenesis of Lyme arthritis and, above all, underline the importance of
      bacterial lipoproteins as major virulence factors.

PMID- 15248238
TI  - Absence of citrulline-specific autoantibodies in animal models of autoimmunity.

PMID- 15248239
TI  - Interleukin-18 receptor expression in synovial fluid-derived fibroblast-like
      synoviocytes: comment on the article by Kawashima and Miossec.

PMID- 15248240
TI  - Matrix metalloproteinase 9 in the saliva of patients with Sjogren's syndrome:
      comment on the article by Goicovich et al.

PMID- 15248242
TI  - The implications of biologic therapy in ankylosing spondylitis: comment on the
      articles by Brandt et al and Braun et al.

PMID- 15248244
TI  - Sensitivity of dual x-ray absorptiometry to stature and reference data source in
      pediatric patients: comment on the article by Stewart et al.

PMID- 15248246
TI  - Clinical images: Syrinx-induced Charcot shoulder.

PMID- 15248248
TI  - Viruses take their Toll too.

PMID- 15248249
TI  - Virus-induced neuronal apoptosis as pathological and protective responses of the
      host.
AB  - Extensive efforts have been made to elucidate mechanisms by which viruses induce
      apoptosis in cultured neuronal cells. However, little is yet understood about the
      mechanisms of neuronal apoptosis in vivo as well as interpretations of this
      active host response. Here we review recent advances toward understanding these
      topics. The c-Jun N-terminal protein kinase cascade may be an important apoptotic
      mediator in virally infected neurons, which comes in focus as a therapeutic
      target for protecting neurons from death. A novel concept can be proposed that
      virus-induced neuronal apoptosis in the central nervous system may represent a
      pathological host response, while that in the peripheral counterpart, especially
      olfactory receptor neurons, may mediate a protective host response.

PMID- 15248250
TI  - Measles virus receptors: SLAM and CD46.
AB  - The success of vaccination against measles in developed countries has
      significantly reduced the incidence of measles-related morbidity and mortality.
      However, measles is still the leading cause of mortality in children from
      underdeveloped countries due to low vaccination coverage, high transmissibility
      of the measles virus as well as primary and secondary vaccine failure. As with
      any viral disease, the identification of the host molecule to which the measles
      virus binds and gains entry into the host cell is a major step in understanding
      the molecular pathology of the disease. Two cell surface receptors, CD46 and
      signaling lymphocyte-activation molecule (SLAM), have been identified as measles
      virus receptors. CD46 is ubiquitously expressed on all nucleated cells and acts
      as a receptor for the Edmonston strain and all vaccine strains derived from it.
      SLAM is selectively expressed on some T and B cells and is utilised by the
      Edmonston strain and wild-type strains that cannot use CD46 for cell entry.
      Understanding the structural and functional variations in measles virus receptors
      with regard to host response can facilitate the development of new vaccines as
      well as provide new insights into measles virus tropism and pathogenesis and,
      importantly, into possible mechanisms for vaccine non-response. Our review
      focuses on the structure of measles virus receptors, measles virus receptor
      function, isoforms and polymorphic forms.

PMID- 15248251
TI  - Simian virus 40 (SV40) and human cancer: a review of the serological data.
AB  - Serum antibodies are widely utilised as specific and sensitive markers of virus
      infections but they have been employed relatively infrequently in the
      investigation of simian virus 40 (SV40) as a human carcinogen. In the past few
      years, serological data have become available which allow an examination of
      whether SV40 is currently circulating in human communities and if SV40 infection
      is associated with human cancer. The development of EIA with virus-like particles
      (VLPs) of SV40, BKV and JCV has facilitated serological studies. Sera from
      macaques naturally infected with SV40 cross-react unambiguously with BKV and JCV
      VLPs. Tests of over 9000 human sera with different immunological assays reveal a
      common pattern of SV40 reactivity. A small proportion of sera react at low titers
      and this reactivity is unrelated to age or the geographic location of the donor,
      but correlates with the presence and titers of BKV and JCV antibodies. Absorption
      with BKV and JCV VLPs decreases or abolishes the SV40 reactivity of human sera.
      The SV40 reactivity of sera from patients with mesothelioma, osteosarcoma or
      lymphomas, cancers which are reported to be associated with SV40, was similar to
      that in their controls or other comparison groups. The SV40 reactivity of human
      sera appears to be almost entirely a result of cross-reactivity with BKV and JCV
      antibodies. Serological data thus do not support the possibility that SV40 is
      circulating in human communities or that it is associated with human cancer.

PMID- 15248252
TI  - Enterovirus uveitis.
AB  - Enterovirus uveitis (EU) is a new infant eye disease that was first observed in
      1980. Three distinct subtypes of human echoviruses, EV19/K, EV11/A and EV11/B,
      caused five hospital outbreaks of EU in different Siberian cities in 1980-1989,
      affecting approximately 750 children, predominantly below 1 year of age. Sporadic
      EU cases were also retrospectively diagnosed in other regions of Russia and in
      different countries of the Former Soviet Union. The illness was characterised by
      rapid iris destruction and severe complications, including cataract and glaucoma.
      The disease has been a subject of intensive studies and was reproduced in lower
      primates after intraocular inoculation of isolated enterovirus strains.
      Importantly, prototype EV11 and EV19 strains did not induce notable disease in
      experimental monkeys. Some of the EU-causing strains were shown to be similar
      phylogenetically and in their pathogenetic properties to the enterovirus strains
      associated with multisystem hemorrhagic disease of newborns. In this review we
      present a summary of the vast epidemiological, virological, clinical and
      experimental data on this new form of ophthalmic infection.

PMID- 15248253
TI  - Prospects of HIV-1 entry inhibitors as novel therapeutics.
AB  - A great deal of progress has been made in understanding the mechanism of human
      immunodeficiency virus entry into target cells. Landmark discoveries such as the
      identification of viral coreceptors and the structure of a portion of the viral
      envelope protein (Env) bound to its receptor provided important insight into how
      Env mediates fusion of the viral and cellular membranes. This knowledge has been
      successfully applied to the development of inhibitors that target discrete steps
      of the entry process. Some of these compounds efficiently block HIV-1 replication
      in vitro and are currently being evaluated in clinical trials. In this review, we
      will introduce the challenges of antiviral therapy and highlight the need for
      novel therapeutics, such as entry inhibitors, to complement current antiviral
      regimens. The mechanism by which Env mediates HIV-1 entry and the therapeutic
      potential of small molecule inhibitors of this dynamic process will be discussed
      in detail.

PMID- 15248254
TI  - Electronic influences on 3J(C,H) coupling constants via -S-, -S(O)- and -SO2-:
      their determination, calculation and comparison of detection methods.
AB  - 3J(C,H) coupling constants via a sulfur atom in two series of compounds, both
      including a sulfide, a sulfoxide and a sulfone, were detected experimentally and
      calculated by quantum mechanical methods. In the first series (1-3) the coupling
      between a hydrogen, bonded to an sp3 carbon, and an sp2 carbon is treated; the
      second series (4-6) deals with the coupling between a hydrogen, bonded to an sp3
      carbon, and an sp3 carbon. Different pulse sequences (broadband HMBC, SelJres, 1D
      HSQMBC, J-HMBC-2, selective J-resolved long-range experiment and IMPEACH-MBC)
      proved to be useful in determining the long-range 3J(C,H) coupling constants.
      However, the dynamic behaviour of two of the compounds (4 and 6) led to weighted
      averages of the two coupling constants expected (concerning equatorial and axial
      positions of the corresponding hydrogens). DFT calculations proved to be useful
      to calculate not only the 3J(C,H) coupling constants but also the different
      contributions of FC, PSO, DSO and SD terms; the calculation of the Fermi contact
      term (FC) was found to be sufficient for the correct estimation of 3J(C,H)
      coupling constants.

PMID- 15248255
TI  - Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part
      8--monocycloalkanes.
AB  - Carbon-carbon and carbon-hydrogen spin-spin coupling constants were calculated in
      the series of the first six monocycloalkanes using SOPPA and SOPPA(CCSD) methods,
      and very good agreement with the available experimental data was achieved, with
      the latter method showing slightly better results in most cases, at least in
      those involving calculations of J(C,C). Benchmark calculations of all possible 21
      coupling constants J(C,C), J(C,H) and J(H,H) in chair cyclohexane revealed the
      importance of using the appropriate level of theory and adequate quality of the
      basis sets. Many unknown couplings in this series were predicted with high
      confidence and several interesting structural trends (hybridization effects,
      multipath coupling transmission mechanisms, hyperconjugative interactions) were
      elucidated and are discussed based on the present calculations of spin-spin
      couplings.

PMID- 15248256
TI  - Single-crystal 2H NMR of deuterated 1,10-decanedicarboxylic acid included in
      hydrogenated urea channels.
AB  - The intergrowth of 1,10-decanedicarboxylic acid and urea give infinite hydrogen
      bonded chains of the guest included in the hexagonal urea host. A deuterium high
      resolution solid-state NMR study of the selectively deuterated intergrowth
      compound 1,10-decanedicarboxylic acid/hydrogenated urea at variable temperature
      in the range 90 < or = T < or = 300 K was performed on a single crystal. The
      analysis of the second moment as a function of temperature is shown to be
      compatible with the known phase transition occurring near T(c) = 203 K. Moreover,
      the spectra indicate that the orientational disorder is strong, and is compared
      to an axial uniform disorder. For this purpose, the general equation for the
      second moment of a system with uniform two-dimensional axial orientational
      disorder is given, and a method to take into account the non-uniform excitation
      of the pulse sequence is proposed.

PMID- 15248257
TI  - Complete 1H and 13C NMR assignments for two new monodesmoside saponins from
      Pentaclethra macroloba (Willd.) Kuntze.
AB  - A detailed NMR study and full assignments of the 1H and 13C spectral data for two
      novel triterpenoid saponins isolated from the stem bark of Pentaclethra macroloba
      (Willd.) Kuntze are described. Their structures were established using a
      combination of 1D and 2D NMR techniques including 1H,1H-COSY, TOCSY, NOESY, gs
      HMQC and gs-HMBC, and also electrospray ionization mass spectrometry and chemical
      methods. The structures were established as 3beta-O-([O-beta-D-glucopyranosyl-(1-
      >2)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L
      rhamnopyranosyl-(1-->2)]-[O-beta-D-glucopyranosyl-(1-->3)-O-beta-D-glucopyranosyl
      (1-->4)])-alpha-L-arabinopyranosylhederagenin (1) and 3beta-O-)[O-beta-D
      glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1
      ->3)-O-alpha-L-rhamnopyranosyl-(1-->2)]-[O-beta-D-glucopyranosyl-(1-->3)-O-beta-D
      glucopyranosyl-(1-->4)])-alpha-L-arabinopyranosyloleanolic acid (2).

PMID- 15248258
TI  - 29/28, 30/28Silicon, 34/32sulfur and 80/77selenium isotope-induced fluorine
      chemical shifts through two bonds.
AB  - Isotope effects on fluorine chemical shifts induced by heteroatoms bonded
      covalently to a carbon atom bearing fluorine atoms were studied. For each
      compound, the isotope-induced chemical shifts 2delta19F(X) through two bonds were
      measured for the heteroatom (X = 29/28Si, 30/28Si, 34/32S and 80/77Se). The
      1delta19F(13/12C) values for the carbon bonded to the fluorine atoms were also
      recorded. Examination of the 19F NMR data showed homogeneity of the isotope
      induced chemical shifts along the rows of the periodic table and regularity down
      the columns (from 10 to 15 ppb per mass unit for the second row to 0.4 ppb for
      the fourth row). It became negligible for atoms of the fifth row.

PMID- 15248260
TI  - Dihydroagarofurans: the fourth isomer isolated from Cedrelopsis grevei bark oil.
AB  - 4-Epi-cis-dihydroagarofuran was isolated from the bark oil of Cedrelopsis grevei
      and its structure was elucidated by 1D and 2D-NMR spectroscopy.

PMID- 15248259
TI  - 1H and 13C spectral assignment of 2(1H)-pyridone derivatives.
AB  - 1H and 13C NMR spectroscopic data for 4-aryl-3,4-dihydro-6-methyl-2(1H)pyridone
      derivatives were fully assigned by a combination of one- and two- dimensional
      experiments (DEPT, HMBC, HMQC, COSY, NOE).

PMID- 15248261
TI  - The tautomerism of Omeprazole in solution: a 1H and 13C NMR study.
AB  - The tautomerism of 5(6)-methoxy-2-([(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]
      sulfinyl)-1H-benzimidazole (omeprazole) was determined in solution, K(T) = 0.59
      in THF at 195 K, in favor of the 6-methoxy tautomer. The assignment of the
      signals was made by comparison with its two N-methyl derivatives in acetone-d6
      and through theoretical calculations of the absolute shieldings (GIAO/DFT/6
      311++G**).

PMID- 15248265
TI  - Assumptions: taking chemistry in new directions.

PMID- 15248266
TI  - Grid-type metal ion architectures: functional metallosupramolecular arrays.
AB  - Recent advances in supramolecular coordination chemistry allow access to
      transition-metal complexes of grid-type architecture comprising two-dimensional
      arrays of metal ions connecting a set of organic ligands in a perpendicular
      arrangement to generate a multiple wiring network. General design principles for
      these structures involve the thermodynamically driven synthesis of complex
      discrete objects from numerous molecular components in a single overall
      operation. Such supramolecular metal ion arrays combine the properties of their
      constituent metal ions and ligands, showing unique optical, electrochemical, and
      magnetic behavior. These features present potential relevance for nanotechnology,
      particularly in the area of supramolecular devices for information storage and
      processing. Thus, a dense organization of addressable units is represented by an
      extended "grid-of-grids" arrangement, formed by interaction of grid-type arrays
      with solid surfaces.

PMID- 15248267
TI  - Alternative translations of a single RNA message: an identity switch of (2S,3R)
      4,4,4-trifluorovaline between valine and isoleucine codons.

PMID- 15248268
TI  - Highly ordered SnO2 nanorod arrays from controlled aqueous growth.

PMID- 15248269
TI  - Direct observation of bonding and charge ordering in (EDO-TTF)2PF6.

PMID- 15248270
TI  - Platonic gold nanocrystals.

PMID- 15248271
TI  - Magnetic properties of all-organic liquid crystals containing a chiral five
      membered cyclic nitroxide unit within the rigid core.

PMID- 15248272
TI  - Structural origin of the high affinity of a chemically evolved lanthanide-binding
      peptide.

PMID- 15248273
TI  - Structural and mechanistic requirements for methane activation and chemical
      conversion on supported iridium clusters.

PMID- 15248274
TI  - A biopolymer composite material as an anhydrous proton-conducting membrane.

PMID- 15248275
TI  - In situ investigations into chemical processes by electron-energy-resolved X-ray
      absorption spectroscopy.

PMID- 15248276
TI  - Self-organization of oligomeric helical stacks controlled by substrate binding in
      a tobacco mosaic virus like self-assembly process.

PMID- 15248277
TI  - Charge-specific interactions in segmented conducting polymers: an approach to
      selective ionoresistive responses.

PMID- 15248278
TI  - Swellable, redox-active shell-crosslinked organometallic nanotubes.

PMID- 15248279
TI  - A measureable equilibrium between iridium hydride alkylidene and iridium hydride
      alkene isomers.

PMID- 15248280
TI  - Anatomy of a cyclohexatriene: chemical dissection of the pi and sigma frame of
      angular [3]phenylene.

PMID- 15248281
TI  - Catalytic self-screening of cholinesterase substrates from a dynamic
      combinatorial thioester library.

PMID- 15248282
TI  - 13C NMR spectroscopic evaluation of the affinity of carbonyl compounds for carbon
      dioxide under supercritical conditions.

PMID- 15248283
TI  - Adsorption chemistry of sulfur dioxide in hydrated Na-Y zeolite.

PMID- 15248284
TI  - Rate acceleration of the reaction between solid reactants by premixing in
      solution: application to the efficient synthesis of a [2]rotaxane.

PMID- 15248285
TI  - Thermally induced electron transfer in a CsCoFe Prussian blue derivative: the
      specific role of the alkali-metal ion.

PMID- 15248287
TI  - Functional reconstitution of gamma-secretase through coordinated expression of
      presenilin, nicastrin, Aph-1, and Pen-2.
AB  - The gamma-secretase complex has emerged as an unusual membrane-bound aspartyl
      protease with the ability to cleave certain substrate proteins at peptide bonds
      believed to be buried within the hydrophobic environment of the lipid bilayer.
      This cleavage is responsible for a key biochemical step in signaling from several
      different cell-surface receptors, and it is also crucial in generating the
      neurotoxic amyloid peptides that are central to the pathogenesis of Alzheimer's
      disease. Active gamma-secretase is a multimeric protein complex consisting of at
      least four different proteins, presenilin, nicastrin, Aph-1, and Pen-2, with
      presenilin serving as the catalytically active core of the aspartyl protease.
      Presenilin itself undergoes endoproteolytic maturation, a process that is tightly
      regulated during the assembly and maturation of gamma-secretase, and that depends
      on the three cofactors nicastrin, Aph-1, and Pen-2. Recent studies have
      demonstrated that presenilin and its three cofactors are likely to be the major
      proteins needed for functional reconstitution of active gamma-secretase and have
      begun to elucidate the specific functions of the cofactors in the ordered
      assembly of gamma-secretase.

PMID- 15248288
TI  - Activity-regulated cytoskeleton-associated protein Arc is targeted to dendrites
      and coexpressed with mu-opioid receptors in postnatal rat caudate-putamen
      nucleus.
AB  - Dendritic expression of the activity-regulated cytoskeleton-associated protein
      (Arc) is dramatically enhanced by increased synaptic activity in adult brain. We
      used immunocytochemical electron microscopy to determine whether the subcellular
      localization of Arc in developing dendrites corresponds to the peak period of
      synaptogenesis in the postnatal rat caudate-putamen nucleus (CPN). The
      distribution was compared with that of mu-opioid receptors (MORs), whose
      localization in dendritic spines closely parallels excitatory synapse formation
      during postnatal development (Wang et al. [2003] Neuroscience 118:695-708).
      Sections were processed for immunocytochemical detection of antisera against Arc
      or MORs at the beginning (postnatal day 15; P15) and the end (P30) of the peak
      period of synaptogenesis in rat CPN. At P15, immunolabeling for Arc showed a
      punctate distribution in the cytoplasm of dendritic shafts, some of which was
      associated with polyribosomes. In some spiny dendrites, Arc immunoreactivity was
      more intensely localized in putative spines than in their parental dendrites,
      whereas, in other spiny dendrites, Arc labeling was restricted in the shafts.
      Many dendritic shafts and spines also showed immunoreactivity for MORs, although
      dually labeled spines were less numerous than the shafts. At P30, the proportion
      of singly and dually labeled spines significantly increased from 2.0% to 7.5% and
      from 9.5% to 21%, respectively. Arc labeling in spines was more detectable
      beneath the postsynaptic density or at extrasynaptic sites on the plasma
      membrane. Our results suggest a correlation between Arc expression in dendritic
      spines during postnatal development and the onset of synaptogenesis in opioid
      responsive neurons in the rat CPN.

PMID- 15248289
TI  - Isolation of retinal progenitor cells from post-mortem human tissue and
      comparison with autologous brain progenitors.
AB  - The goal of the present study was threefold: to determine whether viable human
      retinal progenitor cells (hRPCs) could be obtained from cadaveric retinal tissue,
      to evaluate marker expression by these cells, and to compare hRPCs to human brain
      progenitor cells (hBPCs). Retinas were dissected from post-mortem premature
      infants, enzymatically dissociated, and grown in the presence of epidermal growth
      factor and basic fibroblast growth factor. The cells grew as suspended spheres or
      adherent monolayers, depending on culture conditions. Expanded populations were
      banked or harvested for analysis by RT-PCR, immunocytochemistry, and flow
      cytometry. hBPCs derived from forebrain specimens from the same donors were grown
      and used for RT-PCR. Post-mortem human retinal specimens yielded viable cultures
      that grew to confluence repeatedly, although not beyond 3 months. Cultured hRPCs
      expressed a range of markers consistent with CNS progenitor cells, including
      nestin, vimentin, Sox2, Ki-67, GD2 ganglioside, and CD15 (Lewis X), as well as
      the tetraspanins CD9 and CD81, CD95 (Fas), and MHC class I antigens. No MHC class
      II expression was detected. hRPCs, but not hBPCs, expressed Dach1, Pax6, Six3,
      Six6, and recoverin. Minority subpopulations of hRPCs and hBPCs expressed
      doublecortin, beta-III tubulin, and glial fibrillary acidic protein, which is
      consistent with increased lineage restriction in subsets of cultured cells.
      Viable progenitor cells can be cultured from the post-mortem retina of premature
      infants and exhibit a gene expression profile consistent with immature
      neuroepithelial cells. hRPCs can be distinguished from hBPC cultures by the
      expression of retinal specification genes and recoverin.

PMID- 15248290
TI  - Heterogeneity between hippocampal and septal astroglia as a contributing factor
      to differential in vivo AMPA excitotoxicity.
AB  - Astroglial participation in the regional differences of vulnerability to alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced
      neurodegeneration was investigated in the rat hippocampus and medial septum using
      L-alpha-aminoadipate (alpha-AA) as a specific astroglial toxin. alpha-AA was
      microinjected in the hippocampus and the medial septum and a time-course study
      was carried out between 2 hr and 3 days. When compared to controls,
      microinjection of alpha-AA in the hippocampus induced within 3 days a reversible
      loss of glial fibrillary acidic protein (GFAP) immunostaining and a microglial
      reaction without any neuronal loss, whereas in the medial septum it caused no
      effects on astroglial, microglial, or neuronal populations. Differences in
      hippocampus and medial septum vulnerability were also evidenced when alpha-AA was
      co-injected with AMPA and neurodegeneration was assessed in terms of neuronal
      loss, glial reactions, calcification, and atrophy of the area. In the
      hippocampus, alpha-AA increased AMPA excitotoxicity with marked disorganization
      of all hippocampal subfields, increased neuronal loss, a more important
      astroglial reaction, a larger area of microgliosis, and a greater abundance of
      calcium deposits. By contrast, in the medial septum alpha-AA did not modify any
      parameter of the AMPA-induced lesion. In conclusion, the presence of different
      astroglial populations in hippocampus and medial septum results in a different
      participation to AMPA excitotoxicity that may determine, at least in part, the
      specific regional vulnerability to neurodegeneration.

PMID- 15248291
TI  - Enhanced production and proteolytic degradation of insulin-like growth factor
      binding protein-2 in proliferating rat astrocytes.
AB  - Insulin-like growth factors (IGFs) protect neurons, are important for
      oligodendrocyte survival and myelin production, and stimulate the proliferation
      of astrocytes. The effects of IGFs are regulated by a family of IGF binding
      proteins (IGFBPs). Astrocytes express predominantly IGFBP-2. In the present
      study, primary neonatal rat astrocytes were cultivated in a chemically defined
      medium to initiate a differentiated cell status. After stimulation with fetal
      calf serum, astrocytes became hypertrophic and increased proliferation. Western
      blot analysis of cell lysate of proliferating astrocytes displayed an increased
      expression of IGFBP-2. This finding was supported by immunocytochemical images.
      Semiquantitative polymerase chain reaction analysis demonstrated equal mRNA
      levels in both differentiated and proliferating astrocytes, suggesting that the
      increase in IGFBP-2 production in proliferating astrocytes was exerted at the
      translational level. Concentrated medium of proliferating cells, however,
      displayed lower levels of IGFBP-2 than differentiated cells. When recombinant
      IGFBP-2 was incubated with culture media, we found degradation in the medium of
      proliferating cells, but not in medium of differentiated cells. This degradation
      could be inhibited with protease inhibitors, indicating that lower levels of
      IGFBP-2 in the medium of proliferating astrocytes are due to the presence of
      proteases. Our results suggest that, in proliferating astrocytes, IGFBP-2 may
      help target IGFs to IGF-1 receptors, and IGFBP-2 proteases may play a role in
      enhancing the availability of IGFs.

PMID- 15248292
TI  - Cerebrospinal fluid immunoglobulin G promotes oligodendrocyte progenitor cell
      migration.
AB  - Multiple sclerosis (MS) is characterized by demyelination of the CNS with
      associated neurological deficits. Remyelination can occur but is often
      incomplete. The process of myelin repair requires the proliferation and migration
      of oligodendrocyte progenitor cells (OPC) into the lesion from the neighboring
      areas. OPC migration is altered by several factors, including antibodies that
      bind to OPC surface proteins. We have previously reported elevated anti
      OSP/claudin-11 antibodies in the cerebrospinal fluid (CSF) of MS patients and
      that anti-OSP/claudin-11 antibodies generated in rabbits can inhibit OPC
      migration. In the study presented here, we investigated the effect of CSF IgG
      from MS patients and controls on OPC migration in culture. Rat OPC cultured with
      CSF from MS patients tended to migrate more than those cultured with control CSF,
      but this did not reach statistical significance. To determine whether the IgG
      fraction in the CSF influenced migration, we removed it using protein-A
      sepharose. A dramatic decrease in OPC migration was found in both MS (45 +/- 24
      vs.16 +/- 9) and control (40 +/- 19 vs. 22 +/- 13) samples after IgG was removed
      (P <.05). Anti-OSP/claudin-11 antibody concentration did not significantly
      correlate with OPC migration. These data demonstrate that CSF IgG promotes OPC
      migration. Identification of the specific IgG fraction responsible for this
      effect could lead to novel therapies to promote recovery in MS.

PMID- 15248293
TI  - FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in
      experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated
      neuroprotection in a model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
      (CNS) in which demyelination and axonal loss result in permanent neurologic
      disability. We examined the neuroprotective property of the immunosuppressant
      FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and
      cyclosporin A (CsA) in a chronic relapsing experimental autoimmune
      encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by
      subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in
      complete Freund's adjuvant. At the onset of paralysis, 12-14 days after
      immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg),
      FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30%
      dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity
      of the initial disease and suppressed relapses. FK1706 did not significantly
      alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity
      of the initial episode of EAE but did not alter relapses. In the thoracic spinal
      cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P <
      0.001) reduced the extent of damage in the dorsal, lateral, and ventral white
      matter by a mean of up to 95, 68, and 30%, respectively. A nonimmunosuppressant
      dose of FK506 (0.2 mg/kg) also significantly (P < 0.001) reduced the extent of
      damage in the spinal cord by a mean of up to 45%. Other dosages of these
      compounds were ineffective. FK506 markedly protects against demyelination and
      axonal loss in this MS model through immunosuppression and neuroprotection.

PMID- 15248294
TI  - Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia.
AB  - Physical activity has been shown to be neuroprotective in lesions affecting the
      basal ganglia. Using a treadmill exercise paradigm, we investigated the effect of
      exercise on neurorestoration. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-lesioned mouse model provides a means to investigate the effect of
      exercise on neurorestoration because 30-40% of nigrostriatal dopaminergic neurons
      survive MPTP lesioning and may provide a template for neurorestoration to occur.
      MPTP-lesioned C57 BL/6J mice were administered MPTP (four injections of 20 mg/kg
      free-base, 2 hr apart) or saline and divided into the following groups: (1).
      saline; (2). saline + exercise; (3). MPTP; and (4) MPTP + exercise. Mice in
      exercise groups were run on a motorized treadmill for 30 days starting 4 days
      after MPTP lesioning (a period after which MPTP-induced cell death is complete).
      Initially, MPTP-lesioned + exercise mice ran at slower speeds for a shorter
      amount of time compared to saline + exercise mice. Both velocity and endurance
      improved in the MPTP + exercise group to near normal levels over the 30-day
      exercise period. The expression of proteins and genes involved in basal ganglia
      function including the dopamine transporter (DAT), tyrosine hydroxylase (TH), and
      the dopamine D1 and D2 receptors, as well as alterations on glutamate
      immunolabeling were determined. Exercise resulted in a significant downregulation
      of striatal DAT in the MPTP + exercise compared to MPTP nonexercised mice and to
      a lesser extent in the saline + exercised mice compared to their no-exercise
      counterparts. There was no significant difference in TH protein levels between
      MPTP and MPTP + exercise groups at the end of the study. The expression of
      striatal dopamine D1 and D2 receptor mRNA transcript was suppressed in the saline
      + exercise group; however, dopamine D2 transcript expression was increased in the
      MPTP + exercise mice. Immunoelectron microscopy indicated that treadmill exercise
      reversed the lesioned-induced increase in nerve terminal glutamate immunolabeling
      seen after MPTP administration. Our data demonstrates that exercise promotes
      behavioral recovery in the injured brain by modulating genes and proteins
      important to basal ganglia function.

PMID- 15248295
TI  - Upregulation of annexins I, II, and V after traumatic spinal cord injury in adult
      rats.
AB  - The posttraumatic inflammatory reaction contributes to progressive tissue damage
      after spinal cord injury (SCI). Annexins, a family of structurally related
      calcium- and phospholipid-binding proteins, have potent anti-inflammatory effects
      by inhibiting the activity of phospholipase A(2) (PLA(2)), a key enzyme
      responsible for inflammation and cytotoxicity. We investigated spatiotemporal
      expression of annexins I, II, and V after a contusive SCI using the New York
      University impact device (a 10-g rod, height 12.5 mm) in adult rats. Western blot
      analysis revealed that annexin I expression increased at 3 days after injury,
      peaked at 7 days (1.75-fold above the baseline level; P < 0.01), started to
      decline at 14 days, and returned to the baseline level at and beyond 28 days post
      injury. The expression of annexin II started to increase at 3 days, reached its
      maximal level at 14 days (2.73-fold; P < 0.01), remained at a high level up to 28
      days, and then declined to the basal level by 56 days after injury. Annexin V
      expression started at 3 days, reached its maximal level at 7 days (1.61-fold; P <
      0.05) and remained at this level until 56 days after injury. RT-PCR results
      confirmed expression of all three annexins at the mRNA level after SCI.
      Immunohistochemistry and immunofluorescence double-labeling analyses revealed
      that increased annexins I, II, and V were localized in neurons and glial cells.
      The present study thus revealed increased expression of the three annexin
      isoforms after moderate contusive SCI. The precise role of annexins in
      posttraumatic inflammation and neuroprotection after SCI remains to be
      determined.

PMID- 15248296
TI  - Changes in GABA transporters in the rat hippocampus after kainate-induced
      neuronal injury: decrease in GAT-1 and GAT-3 but upregulation of betaine/GABA
      transporter BGT-1.
AB  - The gamma-aminobutyric acid (GABA) transporters GAT-1, GAT-2, GAT-3, and BGT-1
      have been cloned and identified according to their differential amino acid
      sequences and pharmacologic properties. In contrast to GAT-1, -2, or -3, BGT-1 is
      capable of utilizing both GABA and betaine as substrates. Betaine has been
      suggested to be a protective osmolyte in the brain. Because changes in expression
      of GABA transporters/BGT-1 might result in alterations in levels of GABA/betaine
      in the extracellular space, with consequent effects on neuronal excitability or
      osmolarity, the present study was carried out to explore expression of GABA
      transporters in the rat hippocampus after kainate-induced neuronal injury. A
      decrease in GAT-1 and GAT-3 immunostaining but no change in GAT-2 staining was
      observed in the degenerating CA subfields. In contrast, increased BGT-1
      immunoreactivity was observed in astrocytes after kainate injection. BGT-1 is a
      weak transporter of GABA in comparison to other GABA transporters and the
      increased expression of BGT-1 in astrocytes might be a protective mechanism
      against increased osmotic stress known to occur after excitotoxic injury. On the
      other hand, excessive or prolonged BGT-1 expression might be a factor
      contributing to astrocytic swelling after brain injury.

PMID- 15248297
TI  - Calpain inhibitor 2 prevents axonal degeneration of opossum optic nerve fibers.
AB  - The ultrastructural change that characterizes the onset of Wallerian degeneration
      is the disintegration of axoplasmic microtubules and neurofilaments, which are
      converted into an amorphous and granular material, followed by myelin breakdown.
      The mechanism underlying such processes is an increase in the amount of
      intracellular calcium, leading to activation of proteases called calpains. The
      aim of this study was to evaluate by quantitative ultrastructural analysis
      whether nerve fibers can be preserved by the use of an exogenous inhibitor of
      these proteases (calpain inhibitor-2, Mu-F-hF-FMK), after optic nerve crush. For
      that, the left optic nerves of opossums, Didelphis aurita, were crushed with the
      aid of a fine forceps, and half of them received a calpain inhibitor mixed with
      Elvax resin. Ninety-six hours after the lesion, the animals were reanesthetized
      and transcardially perfused, and the optic nerves were removed, the right ones
      being used as normal nerves. Afterward, the optic nerves were dissected and
      processed for routine transmission electron microscopy and quantitative and
      statistical analysis. The results of this analysis showed that the group that
      received the calpain inhibitor presented a reduction of astrogliosis, maintaining
      the optic nerve structure in an organized state; a significant decrease in the
      number of degenerating fibers; and a significant increase in the number of fibers
      with preserved cytoskeleton and preservation of axonal and myelin area and
      integrity, reducing the enlargement and edema of the axon. In conclusion, our
      findings suggest that calpain inhibitor is able to provide neuroprotection of the
      central nervous system fibers after a crush lesion.

PMID- 15248298
TI  - Biolistic expression of the macrophage colony stimulating factor receptor in
      organotypic cultures induces an inflammatory response.
AB  - The receptor for macrophage colony-stimulating factor (M-CSFR; c-fms) is
      expressed at increased levels by microglia in Alzheimer's disease (AD) and in
      mouse models for AD. Increased expression of M-CSFR on cultured microglia results
      in a strong proinflammatory response, but the relevance of this cell culture
      finding to intact brain is unknown. To determine the effects of increased
      microglial expression of M-CSFR in a complex organotypic environment, we
      developed a system for biolistic transfection of microglia in hippocampal slice
      cultures. The promoter for the Mac-1 integrin alpha subunit CD11b is active in
      cells of myeloid origin. In the brain, CD11b expression is restricted to
      microglia. Constructs consisting of the promoter for CD11b and a c-fms cDNA or an
      enhanced green fluorescent protein (EGFP) cDNA were introduced into monotypic
      cultures of microglia, neurons, and astrocytes. Strong CD11b promoter activity
      was observed in microglia, whereas little activity was observed in other cell
      types. Biolistic transfection of organotypic hippocampal cultures with the
      CD11b/c-fms construct resulted in expression of the c-fms mRNA and protein that
      was localized to microglia. Furthermore, biolistic overexpression of M-CSFR on
      microglia resulted in significantly increased production by the hippocampal
      cultures of the proinflammatory cytokines interleukin (IL)-1alpha macrophage
      inflammatory protein (MIP-1alpha), and trends toward increased production of IL-6
      and M-CSF. These findings demonstrate that microglial overexpression of M-CSFR in
      an organotypic environment induces an inflammatory response, and suggest that
      increased microglial expression of M-CSFR could contribute to the inflammatory
      response observed in AD brain.

PMID- 15248299
TI  - In silico analysis of gene expression profiles in the olfactory mucosae of aging
      senescence-accelerated mice.
AB  - We utilized high-density Affymetrix oligonucleotide arrays to investigate gene
      expression in the olfactory mucosae of near age-matched aging senescence
      accelerated mice (SAM). The senescence-prone (SAMP) strain has a significantly
      shorter lifespan than does the senescence-resistant (SAMR) strain. To analyze our
      data, we applied biostatistical methods that included a correlation analysis to
      evaluate sources of methodologic and biological variability; a two-sided t-test
      to identify a subpopulation of Present genes with a biologically relevant P-value
      <0.05; and a false discovery rate (FDR) analysis adjusted to a stringent 5% level
      that yielded 127 genes with a P-value of <0.001 that were differentially
      regulated in near age-matched SAMPs (SAMP-Os; 13.75 months) compared to SAMRs
      (SAMR-Os, 12.5 months). Volcano plots related the variability in the mean
      hybridization signals as determined by the two-sided t-test to fold changes in
      gene expression. The genes were categorized into the six functional groups used
      previously in gene profiling experiments to identify candidate genes that may be
      relevant for senescence at the genomic and cellular levels in the aging mouse
      brain (Lee et al. [2000] Nat Genet 25:294-297) and in the olfactory mucosa
      (Getchell et al. [2003] Ageing Res Rev 2:211-243), which serves several functions
      that include chemosensory detection, immune barrier function, xenobiotic
      metabolism, and neurogenesis. Because SAMR-Os and SAMP-Os have substantially
      different median lifespans, we related the rate constant alpha in the Gompertz
      equation on aging to intrinsic as opposed to environmental mechanisms of
      senescence based on our analysis of genes modulated during aging in the olfactory
      mucosa.

PMID- 15248300
TI  - Comparative study of cell culture and purification methods to obtain highly
      enriched cultures of proliferating adult rat Schwann cells.
AB  - We present here a fast protocol that could be used to obtain highly purified
      cultures of maximal proliferating adult rat Schwann cells. These adult rat
      Schwann cells can be transfected in a nonbiological way using the physical
      transfection method of electroporation. Schwann cells are decisive in recovery of
      peripheral nerves after injury. In a clinical context, the use of enriched adult
      Schwann cells is necessary for autologous cell transplantation within nerve
      transplants for peripheral nerve repair. Different parameters such as tissue
      preparation, culture conditions, and protocols for enrichment, elevation of
      proliferation rates, and transfection were evaluated in cell cultures harvested
      from adult rat peripheral nerves. Cell preparation from in vivo predegenerated
      adult rat sciatic nerves combined with the use of melanocyte growth medium
      supplemented with forskolin, fibroblast growth factor (FGF)-2, and pituitary
      extract as a selective, serum-free culture medium, with a secondary cell
      enrichment step using specific detachment, resulted in highly enriched cultures
      of adult rat Schwann cells (>90%) with enhanced proliferation rates (>or=40%).
      About 20% of these adult Schwann cells could be modified genetically using an
      optimized electroporation protocol.

PMID- 15248301
TI  - Analysis of galactocerebrosidase activity in the mouse brain by a new
      histological staining method.
AB  - Gene therapy of galactocerebrosidase (GALC) deficient mice (Twitcher mutants)
      requires a fast and sensitive assay to detect transduced cells in vitro and in
      vivo. We have developed a new rapid histochemical method that specifically
      detects GALC activity in situ in neural cells using 5-Br-3Cl-beta
      galactopiranoside (X-Gal) in the presence of taurodeoxycholic and oleic acids to
      enhance suspension of the substrate at low pH. Using this method, we observed
      robust X-Gal staining in diverse neuronal populations and interfascicular
      oligodendrocytes in sections from normal mouse brain. In contrast, sections of
      Twitcher brain did not show a specific staining pattern in neurons or glial
      cells. The availability of this new sensitive and rapid in situ detection assay
      is fundamental for the follow-up of Twitcher mice under gene or cellular
      therapies to correct central GALC deficiency.

PMID- 15248302
TI  - Failed intrathecal analgesia following severe, terminal cancer pain.

PMID- 15248303
TI  - Percholate debate grows.

PMID- 15248304
TI  - Expanding the vision of environmental health at UNC-CH.

PMID- 15248305
TI  - [A 78-year-old man with anterior chest pain].

PMID- 15248306
TI  - Occupational exposures, anatomic location, and geographic distribution of
      laryngeal cancer.

PMID- 15248307
TI  - Re: No increased risk of non-Hodgkin's lymphoma with steroids, estrogens and
      psychotropics (Netherlands).

PMID- 15248308
TI  - Pay for ED call?

PMID- 15248309
TI  - Up close and personal.

PMID- 15248310
TI  - Chalk and cheese.

PMID- 15248311
TI  - Chlamydia.

PMID- 15248312
TI  - To eliminate racial/ethnic disparities, hospitals must standardize data
      collection.

PMID- 15248313
TI  - AMA policy: grassroots to global--what it is and how you can get involved.

PMID- 15248314
TI  - Dawn of a new kind of parenthood.

PMID- 15248315
TI  - A bad case of not asking for consent.

PMID- 15248316
TI  - We hold these freedoms to be self-evident... [interview by Liz Else].

PMID- 15248317
TI  - More than making babies: in vitro fertilization is only a beginning.

PMID- 15248318
TI  - A self-perpetuating treatment: humatrope and the medicalization of social
      problems.

PMID- 15248321
TI  - Disease and life-sustaining treatment.

PMID- 15248322
TI  - Physicians and the burden of medical error.

PMID- 15248323
TI  - [Interpretation session in general radiology. Case No. 2: Digestive system
      imaging].

PMID- 15248324
TI  - [Interpretation session in general radiology. Case No. 3: Urinary disease. Cyst
      of the seminal vesicle with agenesis of homolateral kidney].

PMID- 15248325
TI  - [Interpretation session in general radiology. Case No. 4: Cardiovascular system.
      Single ventricle treated with total cavo-pulmonary anastomosis or Fontan's
      procedure].

PMID- 15248326
TI  - [Interpretation session in general radiology. Case No. 5: Pediatrics. Juvenile
      spondylarthropathy].

PMID- 15248327
TI  - Proton magnetic resonance spectroscopic imaging can predict length of survival in
      patients with supratentorial gliomas.

PMID- 15248328
TI  - [Interpretation session in general radiology. Case No. 6: Polysplenia syndrome].

PMID- 15248329
TI  - An easy-to-use intraoperative digital videography, still photography, and X-ray
      capture system.

PMID- 15248330
TI  - [Interpretation session in general radiology. Case No. 7: Urinary pathology. Von
      Hippel Lindau disease].

PMID- 15248331
TI  - [Interpretation session in general radiology. Case No. 8: Cardiovascular system.
      Fallot tetralogy with pulmonary atresia].

PMID- 15248332
TI  - Concussion in professional football: reconstruction of game impacts and injuries.

PMID- 15248334
TI  - Concussion in professional football: reconstruction of game impacts and injuries.

PMID- 15248333
TI  - [Interpretation session in neuroradiology. Case No. 1: Meningo-encephalic and
      pulmonary sarcoidosis discovered incidentally during follow-up of hypophyseal
      microadenoma].

PMID- 15248335
TI  - [Interpretation session in neuroradiology. Case No. 2: Tuberculous meningitis
      with diffuse pachymeningitis and cervical centro-medullary abscess in
      immunosuppressed patient].

PMID- 15248336
TI  - Conservative neurological management of intracranial epidural abscesses in
      children.

PMID- 15248338
TI  - Poor-grade aneurysmal subarachnoid hemorrhage: outcome after treatment with
      urgent surgery.

PMID- 15248337
TI  - [Interpretation session in neuroradiology. Case No. 3: Cerebral abscess with
      vascular malformation in Rendu-Osler disease. Associated pulmonary fistula].

PMID- 15248339
TI  - [Interpretation session in neuroradiology. Case No. 4: Transalar trans-sphenoidal
      meningo-encephalocele disclosed by pneumococcal meningitis. Associated type 1
      Arnold-Chiari malformation].

PMID- 15248340
TI  - Thalamic deep brain stimulation for essential tremor: relation of lead location
      to outcome.

PMID- 15248341
TI  - [Interpretation session in neuroradiology. Case No. 5: Pure meningeal hemorrhage
      caused by dural fistula with cortical venous return from the posterior fossa].

PMID- 15248342
TI  - Consumer-driven: be careful.

PMID- 15248343
TI  - Creating an IT culture.

PMID- 15248344
TI  - Chaplains and the bottom line.

PMID- 15248345
TI  - Ronald Finn.

PMID- 15248347
TI  - Treatment of large distal extremity skin wounds with autogenous full-thickness
      mesh skin grafts in 5 cats.
AB  - Five cats with large, distal extremity abrasion wounds were treated with an
      autogenous, full-thickness, mesh skin graft. Survival of the mesh grafts in all
      five cats was considered between 90 and 100%. Successful grafting requires
      asepsis, an adequately prepared recipient bed consisting of healthy granulation
      tissue, proper harvesting and preparation of the graft, meticulous surgical
      technique and strict postoperative care. Factors that are essential for the
      survival of skin grafts include good contact between the graft and the recipient
      bed, normal tension on the sutured graft, strict immobilization after grafting
      and prevention of accumulation of blood or serum under the graft. Meshing the
      graft provides more graft flexibility over uneven surfaces and allows adequate
      drainage. In contrast to previous proposals, the authors recommend no bandage
      change before the fourth day after grafting. Full-thickness mesh skin grafting
      can be used to successfully treat large distal skin wounds in cats.

PMID- 15248346
TI  - [Congenital malformations of the tricuspid valve in domestic carnivores: a
      retrospective study of 50 cases].
AB  - A retrospective study was done on 14 cats and 36 dogs diagnosed with right
      atrioventricular valve malformations (RAVM), either tricuspid dysplasia (n = 38)
      or Ebstein's anomaly (n = 12). Comparison with a large reference population
      including 85 250 animals allowed an epidemiologic analysis of these RAVM,
      demonstrating that Labrador, Boxer and Chartreux cats had a 35, 7 and 11-fold
      higher risk respectively to be affected by one of these heart diseases than other
      breeds, without sexual predisposition. In 93% of cases, cardiac auscultation
      revealed a heart murmur, whose grade was not significantly correlated with the
      echographic stages of the valvular disease. The echocardiographic examination
      confirmed the frequent association between RAVM and other congenital anomalies,
      particularly mitral dysplasia, in 84% and 20% of tricuspid dysplasia and Ebstein
      anomaly respectively. Last, the prognosis of RAVM was worsened by atrial
      fibrillation and right-sided heart failure.

PMID- 15248348
TI  - [The influence of centrifugation on quality and freezability of stallion semen].
AB  - The aim of the present study was to investigate the influence of various
      centrifugation methods on sperm loss and quality of frozen-thawed semen. From at
      a total of 8 Warmblood stallions of the National Stud Farm in Avenches, 3
      ejaculates each were collected and seminal plasma was removed using 3 different
      centrifugation regimes. In method I (reference method) centrifugation occurred by
      a speed of 600 x g during 10 minutes. In method II 1000 x g was used during 2
      minutes while in method III centrifugation was performed by 2000 x g during 2
      minutes. After centrifugation 90%, of the supernatant was removed and sperm loss
      calculated. After resuspension of the pellet with freezing medium, functional
      membrane integrity was evaluated by HOS-test and motility determined. In frozen
      thawed semen motility, viability as well as functional membrane integrity (HOS
      test) and acrosome status using chlortetracyclinassay (CTA) were assessed. Our
      results demonstrate that mean sperm loss (I, 1.9%; II, 8.7%; III, 3.7%) was
      significantly (P < 0.05) different between the three centrifugation regimes.
      Regarding semen quality of frozen-thawed semen, HOS in method III (52.1%) was
      significantly lower than in methods I (55.5%) and II (55.3%). Evaluation of the
      acrosome status by CTA showed that more than 70% of sperm cells were capacitated
      and 25% capacitated and acrosome reacted. From our results we conclude that sperm
      loss and functional membrane integrity (HOS-test) in frozen-thawed semen were
      significantly influenced by the centrifugation regime. Therefore, stallion semen
      should be centrifuged at 600 x g during 10 minutes before freezing in order to
      obtain low sperm loss and a good quality of frozen-thawed semen.

PMID- 15248349
TI  - [Tetanus in cats: 3 case descriptions].
AB  - Three cats with spasticity on one leg or on all four limbs were presented between
      1996 and 1998 at the Department of clinical veterinary medicine, Section of
      neurology, Vetsuisse-Faculty of Bern. The presumptive diagnosis was tetanus. A
      focal form was present in two cases and generalised tetanus in one cat. All cats
      had a history of injury at the affected legs respectively at the neck. The first
      clinical signs were seen between two days and three weeks after injury. The
      bacteriologic examination of serous fluid from the site of injury revealed an
      infection with Clostridium. EMG in one cat during anaesthesia showed motor united
      potentials (MUPs) on the spastic leg. All patients received antibiotics
      (Penicillin, respectively Amoxicillin/Clavulanic acid and Metronidazol).
      Supportive aid were initially sedation, wound revision and in one cat nutrition
      through oesophageal sonde. In a second phase physiotherapy was performed. All
      three animals were significantly better after a couple of weeks, two cats were
      without symptoms after eight and five weeks respectively.

PMID- 15248352
TI  - An overview of blood pressure regulation associated with the kidney.

PMID- 15248353
TI  - Salt, blood pressure, and kidney.

PMID- 15248354
TI  - Involvement of renal sympathetic nerve in pathogenesis of hypertension.

PMID- 15248355
TI  - Blood pressure regulation and renal microcirculation.

PMID- 15248356
TI  - Role of renal eicosanoids in the control of intraglomerular and systemic blood
      pressure during development of hypertension.

PMID- 15248357
TI  - Novel aspects of the renal renin-angiotensin system: angiotensin-(1-7), ACE2 and
      blood pressure regulation.

PMID- 15248358
TI  - Role of aldosterone blockade in the management of hypertension and cardiovascular
      disease.

PMID- 15248359
TI  - Clinical implications of blockade of the renin-angiotensin system in management
      of hypertension.

PMID- 15248361
TI  - Kidney and blood pressure regulation.

PMID- 15248360
TI  - Renal renin-angiotensin system.

PMID- 15248362
TI  - Clinical strategy for the treatment of hypertension in non-diabetic and diabetic
      nephropathy in Japan.

PMID- 15248363
TI  - Angiotensin type 1 receptor blockers in chronic kidney disease.

PMID- 15248364
TI  - Perspectives on pain and depression.
AB  - The health care system is often unsuccessful in the treatment of the patient
      experiencing chronic pain. Chronic pain is often complicated by a variety of
      psychiatric conditions that make it difficult to engage and treat patients. This
      generates frustration and pessimism in the physician. The patient may be
      afflicted by the syndrome of an affective disorder, demoralized by the unintended
      circumstances of their life, unable to meet the demands of stressors because of a
      lack of inherent capacities, or helplessly trapped by poor choices and repeated
      unproductive actions. The physician's interest and the patient's optimism can be
      restored and sustained by utilizing a systematic interdisciplinary approach
      utilizing the four perspectives of diseases, life stories, dimensions, and
      behaviors to evaluate the patient who is disabled by depression and chronic pain.
      The design of a comprehensive treatment plan involves the determination of each
      perspective's contribution to the patient's suffering. The process of formulation
      recognizes that the perspectives are distinct from one another but complementary
      in illuminating the various reasons for a patient's suffering. The perspectives
      offer a recipe for designing a rational treatment plan rather than trying to
      reduce the individual patient's complexity into a one-dimensional construct. This
      approach increases the probability of a successful outcome for both patient and
      physician.

PMID- 15248365
TI  - The psychological behaviorism theory of pain and the placebo: its principles and
      results of research application.
AB  - The psychological behaviorism theory of pain unifies biological, behavioral, and
      cognitive-behavioral theories of pain and facilitates development of a common
      vocabulary for pain research across disciplines. Pain investigation proceeds in
      seven interacting realms: basic biology, conditioned learning, language
      cognition, personality differences, pain behavior, the social environment, and
      emotions. Because pain is an emotional response, examining the bidirectional
      impact of emotion is pivotal to understanding pain. Emotion influences each of
      the other areas of interest and causes the impact of each factor to amplify or
      diminish in an additive fashion. Research based on this theory of pain has
      revealed the ameliorating impact on pain of (1) improving mood by engaging in
      pleasant sexual fantasies, (2) reducing anxiety, and (3) reducing anger through
      various techniques. Application of the theory to therapy improved the results of
      treatment of osteoarthritic pain. The psychological behaviorism theory of the
      placebo considers the placebo a stimulus conditioned to elicit a positive
      emotional response. This response is most powerful if it is elicited by
      conditioned language. Research based on this theory of the placebo that pain is
      ameliorated by a placebo suggestion and augmented by a nocebo suggestion and that
      pain sensitivity and pain anxiety increase susceptibility to a placebo.

PMID- 15248366
TI  - Function, disability, and psychological well-being.
AB  - Disability research in arthritis, as in disability research in general, has
      focused on functional limitations and activities of daily living/instrumental
      activities of daily living (ADL/IADL) disability, and has thus ignored a great
      deal of daily life. Unfortunately, the areas of life that have been ignored may
      be those that are most important to individuals, and may also be the most
      sensitive to the first signs of developing disability. The ability to perform
      valued life activities, the wide range of activities that individuals find
      meaningful or pleasurable above and beyond activities that are necessary for
      survival or self-sufficiency, has strong links to psychological well-being--in
      some cases, stronger links than functional limitations and disability in basic
      activities of daily living. A broader assessment of disability has great
      potential for interrupting the disablement and distress process, thereby
      improving the quality of life of individuals with arthritis. Assessment of the
      effects of arthritis, pain, or other chronic health conditions should expand
      beyond assessment of functional limitations and disability in basic activities to
      include assessment of disability in advanced, valued activities.

PMID- 15248367
TI  - Structural models of comorbidity among common mental disorders: connections to
      chronic pain.
AB  - Patterns of comorbidity among common mental disorders can be understood from the
      perspective of a model that regards mood, anxiety and somatization disorders as
      elements within an internalizing spectrum of disorder, and substance use and
      antisocial behavior disorders as elements within a separate externalizing
      spectrum of disorder. In this chapter, we evaluate the possibility of linking
      this model to literature on chronic pain. Evidence from psychosocial and
      biological perspectives points towards mechanisms that link chronic pain to
      internalizing disorders. Such evidence indicates that the internalizing
      externalizing model may provide a useful framework for suggesting new directions
      for research on connections between chronic pain and mood, anxiety, and related
      disorders and traits.

PMID- 15248368
TI  - Neurobiology of pain.
AB  - The neurobiology of pain has had extensive research directed at identifying the
      mechanisms of nociceptive transmission and integration. Clinical conditions of
      chronic pain including phantom limb pain cannot be explained without an
      understanding of the complex mechanisms of pain regulation. An overview of the
      neurobiological organization of the nociceptive system, from different pain fiber
      types to subcortical and cortical experiential centers, is presented, along with
      a brief description of the known cross talk within the system and between pain
      pathways and those for other information. Finally, interactions between
      affective, executive, and cognitive processes and pain experiences are described
      briefly.

PMID- 15248369
TI  - Complex regional pain syndrome: diagnostic controversies, psychological
      dysfunction, and emerging concepts.
AB  - Complex regional pain syndromes (CRPS) types I and II are neuropathic pain
      disorders that involve dysfunction of the peripheral and central nervous system.
      CRPS type I and type II were known formerly as reflex sympathetic dystrophy and
      causalgia, respectively. Most experts believe that a multidisciplinary approach
      including pharmacotherapy, physiotherapy, and psychotherapy is warranted.
      Historically, there has been considerable controversy regarding this disease
      entity. In particular, the precise mechanism of the sympathetic dysfunction as
      well as the nature of the psychological dysfunction commonly observed in patients
      with CRPS has been the subject of considerable debate. Current strides in our
      understanding of the pathophysiology of this disease have improved treatment
      options.

PMID- 15248370
TI  - Can we prevent a second 'Gulf War syndrome'? Population-based healthcare for
      chronic idiopathic pain and fatigue after war.
AB  - In the 1991 Gulf War less than 150 of nearly 700,000 deployed US troops were
      killed in action. Today, however, over 1 in 7 US veterans of the war has sought
      federal healthcare for related-health concerns, and fully 17% of UK Gulf War
      veterans describe themselves as suffering from the 'Gulf War syndrome', a set of
      poorly defined and heterogeneous ailments consisting mainly of chronic pain,
      fatigue, depression and other symptoms. Even though over 250 million dollars of
      federally funded medical research has failed to identify a unique syndrome, the
      debate regarding potential causes continues and has included oil well smoke,
      contagious infections, exposure to chemical and biological warfare agents, and
      posttraumatic stress disorder. Historical analyses completed since the Gulf War
      have found that postwar syndromes consisting of chronic pain, fatigue, depression
      and other symptoms have occurred after every war in the 20th century. These
      syndromes have gone by a variety of names such as Da Costa's syndrome, irritable
      heart, shell shock, neurocirculatory asthenia, and battle fatigue. Though the
      direct causes of these syndromes are typically elusive, it is clear that war sets
      in motion an undeniable cycle of physical, emotional, and fiscal consequences for
      war veterans and for society. These findings lead to important healthcare
      questions. Is there a way to prevent or mitigate subsequent postwar symptoms and
      associated depression and disability? We argue that while idiopathic symptoms are
      certain to occur following any war, a population-based approach to postwar
      healthcare can mitigate the impact of postwar syndromes and foster societal,
      military, and veteran trust. This article delineates the model, describes its
      epidemiological foundations, and details examples of how it is being adopted and
      improved as part of the system of care for US military personnel, war veterans
      and families. A scientific test of the model's overall effectiveness is
      difficult, yet healthcare systems for combatants and their families are already
      being put to pragmatic tests as troops return from war in Iraq and Afghanistan
      and from other military challenges.

PMID- 15248372
TI  - Opioid prescribing for chronic nonmalignant pain in primary care: challenges and
      solutions.
AB  - Evaluating and treating patients with chronic nonmalignant pain, especially with
      opioid medications, often causes discomfort on the part of primary care
      physicians. A number of patient-, physician-, and system-related issues converge
      to make treating chronic pain a complex matter. Patient-related issues include an
      inability to define a clear anatomic cause for patients' pain, comorbid
      psychiatric conditions, and past and current substance abuse. Physicians lack
      training on the appropriate evaluation and treatment of chronic nonmalignant
      pain, fear creating addicts, and often face intense pharmaceutical industry
      pressure to prescribe medications. A paucity of practical clinical practice
      guidelines, controversy over the effectiveness of opioids on chronic nonmalignant
      pain, and concern about potential legal and regulatory ramifications add to the
      complexity of caring for these patients. Possible multifaceted solutions exist to
      minimize provider discomfort and improve their ability to treat patients
      appropriately. Examples include comprehensive, practical multidimensional
      guidelines on the evaluation and treatment of chronic nonmalignant pain, Web
      based teleconferenced consultations with subspecialists, reduced pharmaceutical
      pressure, enhanced continuing medical education and pregraduate training,
      multispecialty coordinated care of patients with adequate reimbursement for such
      care, and physician access to state-based systems to track opioid prescriptions.

PMID- 15248371
TI  - Opioid effectiveness, addiction, and depression in chronic pain.
AB  - Opioids are a viable treatment for chronic pain, but their use requires
      individualization, specified treatment goals, and patient education. Opioid
      responsiveness is influenced by patient-centered characteristics, including a
      predisposition to opioid side effects, psychological distress, and opioid use
      history; pain-centered characteristics, which involve the temporal pattern,
      rapidity of onset, severity, and type of pain; and drug-centered characteristics
      relating to the impact of specific types of opioids on specific patients. Thus,
      opioid doses should be titrated to achieve a favorable balance between analgesia
      and adverse effects. Opioid therapy can be enhanced through the adjunct
      administration of agents such as NMDA antagonists, calcium channel blockers,
      clonidine, and even low-dose opioid antagonists. Controversy exists over 1) the
      long-term use of opioids for non-cancer pain, and patients receiving opioids for
      long periods must be monitored carefully for signs of addictive and aberrant
      behavior, 2) the impact of opioid therapy on emotional depression in patients
      with chronic pain, and 3) whether opioid therapy causes cognitive impairment in
      the elderly. Our ability to determine the validity of such assertions and the
      exact role of opioids in the treatment of chronic pain will benefit from further
      study.

PMID- 15248373
TI  - To help and not to harm: ethical issues in the treatment of chronic pain in
      patients with substance use disorders.
AB  - Patients with both chronic pain and substance use disorders are increasingly
      encountered in a variety of treatment settings. The treatment of these patients
      raises a number of ethical and patient care issues. Consultation-liaison
      psychiatrists possess the knowledge and skills to constructively address these
      issues. This chapter provides clinicians with a review of clinical and ethical
      dilemmas related to opioid treatment of chronic pain in patients with substance
      use disorders. The core conflict of beneficence and nonmaleficence will be
      explored in relation to the concepts of autonomy, justice, respect for persons,
      confidentiality, and informed consent. The thesis of this discussion focuses on
      the clinician's desire to provide compassionate care and relieve suffering, which
      sometimes conflicts with the clinician's desire to improve functioning, extend
      longevity, and enrich quality of life. A harm reduction model for clinical
      decision making is summarized.

PMID- 15248374
TI  - Visceral hypersensitivity in functional disorders of the upper gastrointestinal
      tract.
AB  - Visceral hypersensitivity is now recognised as a major pathophysiological
      mechanism in functional gastrointestinal disorders of the upper gastrointestinal
      tract. In patients with non-cardiac chest pain and functional dyspepsia, a high
      prevalence of visceral hypersensitivity has been indeed observed. In these
      patients, luminal physiological stimuli can be perceived as unpleasant or even
      painful. Although the fine mechanisms underlying such "aberrant perceptions" are
      yet not fully clarified, it is thought that an altered activation of the gut-wall
      receptors, an altered conduction of sensory inputs at the level of neural
      pathways, or an impaired processing of the sensations at the level of brain, may
      occur along the brain-gut axis. So far, drugs able to reduce hypersensitivity,
      that target each of the constituents of the stimuli-perception chain, have the
      therapeutic potential to reduce visceral hypersensitivity and, thus, to improve
      the symptoms. In this context, the availability of new agonists/antagonists to
      neurotransmitters offers a new exciting tool for the treatment of functional
      disorders of the upper gastrointestinal tract.

PMID- 15248375
TI  - Quadruple therapy as a first-line Helicobacter pylori treatment: past or future?

PMID- 15248376
TI  - Absence of an association of the IBD2 locus gene keratin 8 and inflammatory bowel
      disease in a large genetic association study.

PMID- 15248377
TI  - Twice daily (mid-day and evening) quadruple therapy for H. pylori infection in
      the United States.
AB  - BACKGROUND: Quadruple therapy provided inadequate eradication rate when given
      twice-a-day at breakfast and evening meals. AIM: To test twice daily (mid-day and
      evening) quadruple therapy for Helicobacter pylori eradication. METHODS: This was
      a single-centre pilot study in which H. pylori-infected (positive histology and
      culture and RUT) patients were given 2 x 250 mg of metronidazole and 2 x 250 mg
      of tetracycline, two Pepto-Bismol tablets, plus one 20 mg rabeprazole tablet
      twice-a-day for 14 days. H. pylori status was confirmed 4 or more weeks after the
      end of therapy. RESULTS: Thirty-seven patients including 3 with peptic ulcer
      disease, 19 asymptomatic infected, 4 GERD, and 11 with NUD. Mid-day quadruple
      therapy was successful in 92.3% (95% CI: 79-98%) including 96.2% of those with
      metronidazole-susceptible strains, and in 83.3% (10/12) of those with
      metronidazole-resistant H. pylori. Compliance was 100% by pill count except in
      one individual who stopped medication after 12 days because of side-effects and
      who failed therapy. Moderate or greater side-effects were experienced by five
      patients. CONCLUSION: Twice-a-day, mid-day, quadruple therapy proved effective
      using the combination of bismuth subsalicylate and rabeprazole instead of bismuth
      subcitrate and omeprazole. Detailed studies of different formulations (e.g. 2 x
      250 mg versus 1 x 500 mg of metronidazole or tetracycline) and timing of
      administration (breakfast and evening meal versus mid-day and evening meals) may
      result in significant improvements in H. pylori eradication regimens.

PMID- 15248378
TI  - Keratin 8 Y54H and G62C mutations are not associated with inflammatory bowel
      disease.
AB  - BACKGROUND: Keratin 8 is a major component of intermediate filaments in single
      layered epithelia of the gastrointestinal tract. Keratin 8 deficient mice display
      signs of colitis and diarrhoea characteristic for inflammatory bowel disease.
      Very recently, two keratin 8 mutations, Y54H and G62C, were identified. AIMS: We
      investigated if these keratin 8 missense mutations were associated with
      inflammatory bowel disease. PATIENTS: In total, 217 German patients with Crohn' s
      disease, 131 German patients with ulcerative colitis, and 560 German control
      subjects were enrolled in this study. METHODS: Samples were analysed by PCR
      amplification and subsequent melting curve analysis using fluorescence resonance
      energy transfer probes. RESULTS: The G62C mutation was detected in five (2.3%)
      patients presenting with Crohn's disease and in three (2.3%) with ulcerative
      colitis. In comparison, 9 (1.6%) out of 560 controls were heterozygous for this
      mutation. No patient or control was homozygous for this mutation. Patients
      carrying one mutant allele did not show any noticeable characteristics in their
      corresponding phenotype. In contrast, the Y54H mutation was observed in neither
      any of the 348 patients with inflammatory bowel disease nor in any control
      subject. CONCLUSIONS: Our data indicate that both keratin 8 mutations, G62C and
      Y54H, do not play a relevant pathogenic role in inflammatory bowel disease.

PMID- 15248379
TI  - Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow
      micrometastases.
AB  - BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and
      the presence of bone marrow micrometastases are poor prognostic markers in
      patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these
      tumours is associated with increased metastatic potential in vitro, our
      objectives were to determine the relationship between cyclooxygenase-2 and
      haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients
      with resection of colorectal carcinoma were evaluated (median age: 69.5 years).
      Bone marrow was obtained from all patients from both iliac crests before
      manipulation of the primary tumour. The tumours were of varying stages at
      diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections
      were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical
      technique. Extent of staining was graded depending on the percentage of
      epithelial cells staining positive for cyclooxygenase-2. Micrometastases were
      detected by staining contaminant cytokeratin-18 positive cells in the bone marrow
      aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry)
      methods. Fisher's exact probability test was used to calculate statistical
      significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was
      detected in 72% of the patients. Twelve (38%) patients had bone marrow
      micrometastases detected by either immunohistochemistry or flow cytometry. Of the
      12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased
      expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20
      (45%) patients in whom micrometastases were not detected expressed increased
      levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups
      of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there
      was no further association between cyclooxygenase-2 expression and bone marrow
      micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was
      no association between cyclooxygenase-2 expression and bone marrow
      micrometastases in patients with otherwise localised or disseminated disease.

PMID- 15248380
TI  - Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian
      Association for the Study of the Liver.
AB  - AIM: To define the characteristics of the Italian patient presenting non
      alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 305 patients with
      abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase
      levels for at least 12 months, with no known cause of chronic liver damage, were
      consecutively enrolled in the study. Clinical, routine biochemical and liver
      histology investigations were carried out in all patients. Also evaluated were:
      (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA
      test model; and (c) plasma endotoxaemia, total antioxidant plasma capability,
      tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels.
      Malondialdehyde and 4-hydroxynonenal content were determined on liver samples
      from 120 patients. RESULTS: The majority of patients were young overweight or
      obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia
      (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and
      cytokines were only sporadically altered. Total antioxidant plasma capability was
      decreased in 38.4% of the patients. Eighty percent of the cases had histological
      steatosis with a mild degree of inflammation and fibrosis. Seven patients had
      cirrhosis. Lipid peroxidation markers were increased in 90% of the cases,
      inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin
      and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and
      insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at
      multivariate analysis no single factor was found to be an independent predictor
      of hepatic lesions. CONCLUSIONS: The typical Italian patient with non-alcoholic
      fatty liver disease is a young male, obese, not diabetic, with a variable
      incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define
      the type of liver damage.

PMID- 15248381
TI  - Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a
      dietary/pharmacological treatment. A pilot study.
AB  - BACKGROUND: Previous studies demonstrated that in experimental animals fatty
      liver is associated with reduced hepatic blood flow and that metformin reverses
      steatosis, while no data were reported in humans. AIMS: To evaluate the clinical
      relevance of echo-Doppler measurements and the effects of therapy in non
      alcoholic fatty liver disease. PATIENTS: Twenty patients with biopsy proven non
      alcoholic fatty liver disease. METHODS: Abdominal echo-Doppler examination was
      performed at enrolment and, in 11 patients, after 6 months of
      dietary/pharmacological therapy (metformin 500 mg three times a day). RESULTS:
      Non-alcoholic fatty liver disease was characterised by hepatomegaly, bright
      echotexture and posterior attenuation. Mean portal blood velocity and flow were
      low-normal. Brightness and posterior attenuation significantly correlated with
      fat score in liver biopsies as well as with the hepatic veins spectrum. After
      therapy, echotexture improved and liver volume significantly decreased. Portal
      blood velocity and flow significantly increased, intrahepatic arterial indexes
      decreased and the spectrum of hepatic veins improved. CONCLUSIONS: Fatty liver is
      associated with an impaired hepatic blood flow characterised by increased
      intrahepatic resistances. Vascular changes are reversed by treatment and can be
      measured by echo-Doppler which may be useful to evaluate the natural course of
      non-alcoholic fatty liver disease, and to monitor the putative beneficial effects
      of therapy.

PMID- 15248382
TI  - Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in
      patients with and without preoperative biliary drainage.
AB  - BACKGROUND: It has been suggested that preoperative biliary drainage increases
      the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of
      this study was to assess complications related to biliary stents/drains and
      postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for
      periampullary cancer. PATIENTS: One hundred and eighty-four patients with
      periampullary neoplasms were prospectively selected for neoadjuvant external beam
      radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002.
      METHODS: The data were retrospectively completed and analysed with respect to
      biliary drainage, efficacy and complications of endoscopic biliary stents and
      postoperative morbidity. Patients who had undergone a surgical biliary bypass
      were excluded. RESULTS: Data were completed in 168 patients. One hundred and
      nineteen patients were treated with endoscopic biliary stents, 18 patients had a
      percutaneous biliary drain and 31 patients did not require biliary drainage.
      Hospitalisation for stent-related complications was necessary in 15% of the
      patients with endoscopic biliary stents. Seventy-two patients underwent
      pancreaticoduodenectomy. There was no significant difference in the rate of wound
      infections, intra-abdominal abscesses and overall complications between the
      groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative
      infectious complications are common in patients both with and without
      preoperative biliary drainage. A statistically significant difference in
      complication rates was not observed between these groups.

PMID- 15248383
TI  - Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis with
      unusual initial presentation as fulminant hepatic failure.
AB  - Autoimmune hepatitis and primary biliary cirrhosis are generally easy to
      discriminate on the basis of clinical, laboratory, and histological findings. The
      presence of anti-mitocondrial antibodies seropositivity and cholestatic clinical,
      laboratory, and/or histological features in patients with autoimmune hepatitis
      indicates the overlap syndrome of autoimmune hepatitis and primary biliary
      cirrhosis. Fulminant hepatic failure is an unusual initial form of presentation
      of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. We report
      the case of a 50-year-old woman with autoimmune hepatitis and primary biliary
      cirrhosis overlap syndrome who presented with fulminant hepatic failure.
      Fulminant hepatic failure has a high mortality rate and may require liver
      transplant. Our patient revealed a good response to corticosteroid and
      ursodeoxycholic acid therapy. It is important to identify and distinguish
      autoimmune hepatitis and variant syndromes from other forms of liver disease
      because of response to corticosteroid therapy.

PMID- 15248384
TI  - Sacroileitis and peripheral arthropathy associated with ulcerative colitis:
      effect of infliximab on both articular and intestinal symptoms.
AB  - Infliximab has been proven to be an effective therapy in a miscellany of
      rheumatic diseases and has been approved for the treatment of moderate-to-severe
      Crohn's disease with an inadequate response to conventional therapy and for the
      management of enterocutaneous fistulas. Data about the role of infliximab in
      ulcerative colitis are still controversial. Here, we report a case of a patient
      with sacroileitis and peripheral arthropathy associated with left-sided
      ulcerative colitis who achieved a sustained clinical remission after infliximab
      therapy.

PMID- 15248385
TI  - The use of the anti-tumour necrosis factor monoclonal antibody--infliximab--to
      treat ulcerative colitis: implications and trends beyond the available data.
AB  - The monoclonal antibody to the tumour necrosis factor--infliximab--has recently
      been added to the list of off-label therapeutic means for ulcerative colitis. We
      conducted a descriptive analysis of the results from studies on the use of the
      drug published so far. A total of 187 patients qualified for analysis. They were
      divided into four main categories, including steroid-refractory and responsive
      adults and children. The median frequencies of an early and a sustained response
      were 77 and 44.5%. These data suggest that adult non-steroid-refractory, and
      paediatric patients may respond with the highest frequency. While it is
      obligatory to wait for the yield of the ongoing controlled trials before any
      conclusion on these indications is drawn, the data provide seminal ideas to
      further investigations, including the hypothesis to inaugurate with infliximab a
      top-down strategy for the treatment of inflammatory bowel disease.

PMID- 15248386
TI  - Incidental diagnosis and endoscopic resection of asymptomatic duodenal carcinoid
      during a routine upper gastrointestinal endoscopy.

PMID- 15248387
TI  - The mental health effects of terrorism and traumatic events.

PMID- 15248388
TI  - The state of research on the mental health effects of terrorism.

PMID- 15248389
TI  - Prevention and treatment of the psychological consequences of trauma in children
      and adolescents.

PMID- 15248390
TI  - [From the shelf to the monitor: opportunities and difficulties for psychiatric
      journals switching from paper to on-line].
AB  - The author examines the changes brought about by Internet in the complex field of
      international medical and scientific journals (and psychiatric journals in
      particular), since online versions of the printed publications have been made
      available on the Internet. Attention is focused on the surfeit of these
      scientific journals and on the economic implications of the transformation. The
      article underlines how the international scientific community has become
      conscious of its importance in the production of scientific journals and a
      description of the very innovative Public Library of Science (PLoS) initiative is
      also given. The author illustrates the possible future functioning of scientific
      journals, the so-called "Author pays" model, which is still controversial and
      closes with comments on the increasingly important role played by direct
      communication between scientific community and citizens, including the use of
      specific journals and websites.

PMID- 15248391
TI  - Towards a dynamic description of major depression epidemiology.
AB  - AIMS: The substantial impact of major depression on population health is widely
      acknowledged. To date, health system responses to this condition have been
      largely shaped by observational findings. In the future, health policy decisions
      will benefit from an increasingly integrated and dynamic understanding of the
      epidemiology of this condition. Policy decisions can also be supported by the
      development of decision-support tools that can simulate the impact of alternative
      policy decisions on population health. Markov models are useful both in
      epidemiological modelling and in decision analysis. METHODS: In this project, a
      Markov model describing major depression epidemiology was developed. The model
      employed a Markov Tunnel in order to depict the dependence of recovery
      probabilities on episode duration. Transition probabilities, including incidence,
      recovery and mortality were estimated from Canadian national survey data.
      RESULTS: Episode incidence was approximately 3% per year. Recovery rates declined
      exponentially over time. The model predicted point prevalence at slightly less
      than 1%, agreeing closely with observed prevalence data. CONCLUSIONS:
      Epidemiological models describing the dynamic relationships between major
      depression incidence, prevalence, recovery and mortality can help to integrate
      available epidemiological data. Such models offer an attractive option for
      support of health policy decisions.

PMID- 15248392
TI  - [Attitudes toward disabilities and mental illness in work settings: a review].
AB  - AIMS: The aim of the present work is to analyse employers' and employees'
      attitudes towards the job integration of people with mental illness or disability
      and to highlight the socio-demographic and organizational characteristic that are
      more significantly associated with such attitudes. METHOD: We performed PsycINFO,
      AskERIC and Medline searches for studies published from 1961 to 2002, with key
      words such as attitudes, stigma, schizophrenia, mental illness, disability,
      employers, employees, co-workers and supported employment. RESULTS: Our review of
      the literature showed that the possibility for people with severe mental illness
      or disability to enter job market is limited by the discriminating attitudes of
      employers. The socio-demographic and organizational characteristics, which are
      more significantly associated with employers' more positive attitudes, are:
      dimension of the company, previous positive contact with people with disability
      and employers' high educational level. CONCLUSIONS: Such information could be
      useful to identify and, perhaps, select those companies, which can be predicted
      as more likely to accept people with mental disorders as part of their work
      force; they could also be used to train job applicants to improve their social
      skills. Finally such information could be used to plan specific programs to
      modify attitudes of employees and employers.

PMID- 15248393
TI  - [Prevalence of mental disorder and related treatments in a local jail: a 20-month
      consecutive case study].
AB  - AIMS: To define the prevalence of mental disorder within an Italian local jail
      and to describe main psychiatric treatments provided. METHODS: Cross-sectional
      study of consecutive male prisoners referred, over a twenty-month period, for a
      clinical psychiatric assessment, among population (N = 990) of Casa circondariale
      "Torre del Gallo", Pavia (I); clinical DSM-IV diagnostic assessment and
      retrospective analysis of provided psychiatric treatments (i.e. psychiatric
      visits and pharmacological prescriptions). RESULTS: 191 men (19.3%) had one or
      more current mental disorders (excluding substance misuse), including 13 (1.3%)
      psychosis; 53 (5.4%) mood disorder; 24 (2.4%) anxiety disorder; 26 (2.6%)
      adjustment disorder; 40 (4.1%) personality disorder; 32 (3.2%) personality
      disorder plus mood disorder; 3 (0.3%) mental retardation. Substance- (N = 89,
      47%) and HIV-related (N = 19, 10%) disorders comorbidity is recognised.
      Psychiatric visits are mainly provided to psychosis and personality disorder plus
      mood disorder subgroups. Off-label antipsychotics prescriptions are frequent.
      CONCLUSIONS: The prevalence of mental disorder in this population is higher than
      US and EU averages, and for particular diagnostic subgroups it could be
      underestimated. Psychiatric management in prison should be reorganized according
      to national and European health guidelines.

PMID- 15248394
TI  - [Executive function remediation in schizophrenia: possible strategies and
      methods].
AB  - AIM AND METHOD: The paper is a selective review of the literature on strategies
      and methods of cognitive remediation in schizophrenic disorders. It has been
      focused on the remediation of executive functions and the present hypotheses
      about the possibility of an improvement of the neurocognitive deficit through
      specific interventions. RESULTS AND CONCLUSIONS: People with Schizophrenic
      Disorders have some degree of cognitive deficit that often precede the clinical
      onset not secondary to the pathology characteristics persisting even when the
      positive symptoms have been resolved. The possibility that the neurocognitive
      deficits could be modified by psychological remediation with effects not
      exclusively confined to the cognitive domain has been nowadays accepted and
      numerous studies demonstrate that these interventions are effective and durable
      with a positive impact on social and working abilities, symptomatology and self
      esteem.

PMID- 15248395
TI  - Galvanising mental health research in low-and middle-income countries: role of
      scientific journals.

PMID- 15248396
TI  - [Estimation of the cost in the medical treatment of benign prostatic hyperplasia
      in Navarre, Spain].
AB  - We evaluate the cost and trends in the medical treatment of out patients
      suffering from lower urinary tract symptoms suggestive of clinical benign
      prostatic hyperplasia in Navarre (Spain) between 1998/2002. The estimated number
      of patients increased each year, to 10% of the male population over the age of 50
      in 2002, with a cost of Euros 2,557,236 equivalent to 2.4% of the total drug
      expenditure spending of out patients (Euros 106.6 million). The use of tamsulosin
      tripled and the cost doubled to Euros 807,467 (31.5%) of the total), while the
      rest of alpha-blockers, wit the exception of doxazosin, was stationary.
      Phytotherapy decreased by a third and finasteride follows a slow upward trend.
      The introduction of reference prices set by the Health Department in 2001 to
      reduce medical budget, led to an initial decrease in cost, offsetted in the
      following year due to the incorporation of new patients. In this period, surgery
      for prostate adenoma diminished from 382 patients in 1998 to 270 in 2002 (-30%).

PMID- 15248397
TI  - [Carcinosarcoma of the bladder: report of our cases and review of the
      literature].
AB  - Carcinosarcomas of the bladder are rare. As a result, the natural history of them
      and the best methods of treatment remain uncertain. These tumors tend to be
      rapidly growing, invasive and recur locally. We reviewed our experience with four
      patients presenting between 1995 and 2002. Epidemiology findings, clinical
      aspects, histological features, diagnostic methods, treatment and survival are
      discussed in relation to literature.

PMID- 15248398
TI  - [Phosphotyrosine phosphatase SHP-1, somatostatin and prostate cancer].
AB  - We review the mechanisms involved in prostatic growth based on androgens and
      product of neuroendocrine secretion, with special reference to the role of
      somatostatin (SS) in the inhibition of neoplastic growth. Our contributions in
      the field confirm the antiproliferative effect of SS on the prostate is mediated
      by phosphotyrosine phosphatase SHP-1, that is present in human prostate. This
      enzyme plays a role in the control of prostatic cell proliferation and in the
      progression of prostate cancer. Besides, we consider its presence may determine
      the therapeutic potential of SS in the control of prostate cancer.

PMID- 15248399
TI  - [The natural history of sperm cleareance after vasectomy].
AB  - OBJECTIVE: To study the time required to obtain a negative sperm analysis after
      vasectomy. MATERIAL AND METHODS: We reviewed 239 consecutive vasectomies
      performed between september 1998 and september 1999. All of them were done in an
      ambulatory basis. Follow up interval was 41-853 days (mean 144, median 104). The
      first semen analysis was requested between 1 and 6 months after the surgical
      procedure. If the sample still showed spermatozoa, then a new one was requested
      every two months. Probability of becoming azoospermic was studied with Kaplan
      Meier curves. RESULTS: Persistent spermatozoa could be found in 31 patients (13%)
      at the end of follow-up. Despite having a positive semen analysis, 10 patients
      (4.2%) discontinued medical visits. Time required to obtain a negative sperm
      count ranged from 58 to 362 days (mean 133, median 99). The probability of being
      azoospermic 200 and 260 days after vasectomy was 80-90% respectively. A total of
      328 semen analysis were requested (range 1-4, mean 1.37, median 1) CONCLUSIONS: A
      minimum of 200 days (6.6 months) are needed to clear all the spermatozoa in semen
      after vasectomy in 80% of our patients. Requesting the first semen sample 7
      months after vasectomy is cost-effective, reducing unnecesary medical visits and
      increasing the rentability of this test.

PMID- 15248400
TI  - [Treatment with Doxazosin in 3347 patients with lower urinary tract symptoms.
      Impact on sexual function. The impros study].
AB  - OBJECTIVES: An open, non-comparative, multicenter study was performed to
      ascertain the prevalence in Spain of erectile dysfunction (ED) associated to
      benign prostatic hypertrophy (BPH), with moderate to severe urinary symptoms, and
      to confirm the improvement or disappearance of ED in response to treatment with 4
      mg/day of Doxazosin. METHODS: Out of the 3901 patients recruited 3545 took the
      medication and 3347 completed all the protocol visits. BPH patients were
      considered to have some degree of erectile dysfunction when they reported a
      difficulty for obtaining and/or maintaining an erection in the four weeks prior
      to their inclusion in the study (questions 3 and 4 of the International Index of
      Erectile Function). All the patients were treated with Doxazosin at increasing
      doses: from 1 mg/day up to 4 mg/day thereafter until 6 months of medication were
      completed. RESULTS: The mean number of patients showing erectile dysfunction was
      69.1%, ranging from 48.3% in the 40-49 years age group to 76.3% in the group aged
      from 60 to 69 years. In most Spanish regions, the prevalence of ED ranged from
      76.9% in Cantabria to 67.2% in Aragon. The mean number of patients in whom
      erectile dysfunction disappeared after treatment, with a 95% confidence interval,
      was 4.5%, ranging from 17.5% in the 40-49 age group to 1.1% in the over 70s.
      CONCLUSIONS: ED is a symptom very often associated to BPH, even in relatively
      young men. Doxazosin appears to have a beneficial effect in ED improvement,
      particularly in the younger patients.

PMID- 15248401
TI  - [Prognostic value of DNA ploidy and nuclear morphometry in metastatic prostate
      cancer].
AB  - PURPOSE: To assess the prognostic value of DNA ploidy and nuclear morphometry in
      metastatic prostate cancer after androgenic deprivation treatment. METHODS: Fifty
      four patients with prostate cancer and bone metastases who had undergone
      androgenic suppression treatment were retrospectively studied. The
      deoxyribonucleic acid (DNA) content was analysed by flow cytometry. Nuclear
      morphometry characterized 14 nuclear descriptors. The study also included age,
      Gleason score, T classification, haematocrite, serum albumin, serum alkaline
      phosphatase, serum prostatic acid phosphatase and the amount of metastatic foci
      detected during radioisotope bone scan. Univariate survival analyses were
      performed and Cox's proportional hazards model was used to identify significant
      prognostic factors. To assess how the experimental factors improve the capacity
      of the classical factors for predicting the patients who reach median survival,
      logistic regression multivariate analysis was performed for the classical
      prognostic factors only and after added experimental variables (DNA content and
      Nuclear Area). RESULTS: The univariate survival analyses assigned a prognostic
      value to T category, level of albumin, alkaline phosphatase, Gleason score, bone
      scan, DNA ploidy and mean nuclear area. In the case of the Cox regression model
      only Gleason score, bone scan, mean nuclear area and DNA ploidy provided
      independent prognostic information. In logistic regression for classic prognostic
      factors only Gleason score is significant (sensibility 89.3%, specificity 64%).
      However, when the experimental factors are added, in addition to Gleason score,
      radioisotope bone scan and DNA ploidy are of prognostic value (sensibility 90%
      and specificity 72%). CONCLUSIONS: The study of DNA content and nuclear
      morphometry in the primitive tumor provides independent prognostic information in
      survival analysis for patients with metastatic prostate cancer. However, there is
      limited improvement with respect to the classical factors in predicting survival.
      This questions its utility in the daily clinical usage.

PMID- 15248402
TI  - [Follicular carcinoma of the thyroid manifested initially as asymptomatic primary
      renal neoplasm].
AB  - Metastases in the kidney are rare, evenmore if primary source is thyroid. We
      report the tenth case of metastases in the kidney from thyroid, and it is the
      first to be follicular type and absolutely asymptom. Sonography and computerized
      tomography with suspicion of renal tumour are showed in a asymtom female 75 years
      old. Left partial nephrectomy was perfomed, initially it has been pathologically
      diagnosed as renal clear cells tumour, however the definitive pathologic report
      showed follicular tumour of thyroid. Local and systemic stage was discovered with
      complementary techniques. Sources of metastases in kidney and diagnoses
      techniques are discussed.

PMID- 15248403
TI  - [Intrascrotal metastasis in a renal cell carcinoma].
AB  - The present article reports a case of intrascrotal metastasis of renal
      adenocarcinoma. This is an unusual case. A 66-year-old male patient undewent
      right radical nephrectomy and cavotomy for renal cell carcinoma with renal vein
      infiltration and thrombus in cava. Six months later the patient present with a
      nodulous enlargement intrascrotal and roots of penis. And he died 15 moths after
      nephrectomy. Usually intrascrotal metastases are a late event in the course after
      detection of a renal carcinoma.

PMID- 15248404
TI  - [Extra-anatomic urinary diversion by subcutaneous catheter].
AB  - Percutaneous nephrostomy has been one of most used palliative method of urinary
      diversion to treat cronic renal failure in neoplasic patients. Psychological and
      social factors meke this measure to be rejected by some patients even sin
      situations where this is the only action that would make their survival longer.
      The utilization of ureteral stents provides benefits to a certain percentage of
      patients, not being possible its usage in all the occassions. Urinary
      subcutaneous diversion can be a simple and well tolerated alternative for the
      patient. The following clinic case describes and approach implementing a
      subcutaneous stent in a 60-y-old male with a severe ureteric obstruction after
      failed management by endoscopy or open surgery.

PMID- 15248405
TI  - [Traumatic urethral disruption in women. A rare entity. Report of two cases].
AB  - We present two cases of urethral disruption in women, a very uncommon situation
      because of the anatomical features. Yet it must be always suspected in all women
      under a pelvic politraumatism, for eviting important problems. Both cases are
      traffic politraumatized young girls presenting with pelvic fracture, among
      others. The surgery performed was combined suprapubic-transvaginal approach, even
      in one a previous endoscopic realinement was done, who also needed endoscopic
      complementary treatment: electrofulguration of a fistulous bridge. Outcome of
      both is fine, achieving good continence. We also make a literature review.

PMID- 15248406
TI  - [Intraocular metastatic renal carcinoma presenting as progressive unilateral
      blindness].
AB  - Clear cell renal carcinoma is the most common histological type, representing 70
      80% of all renal carcinomas. Metastases are already present in about 25-30% of
      patients at the time of diagnosis of renal cell carcinoma. Ocular metastasis is
      extremely rare.

PMID- 15248408
TI  - [Acute scrotum: testicular torsion of Morgagni hydatid].

PMID- 15248407
TI  - [Giant retroperitoneal cystic mass: appendiceal mucocele].
AB  - Appendiceal mucocele is a term used to describe the dilatation of the vermiform
      appendix produced by an intraluminal accumulation of mucus. Four pathological
      processes have been described that may lead to an appendiceal mucocele:
      obturation of cecoappendiceal communication, mucosal hyperplasia, mucinous
      cystadenoma and mucinous cystoadenocarcinoma. The most frequent is mucinous
      cystadenoma, seen in 50% of appendiceal mucoceles. 6% of patients with
      appendiceal mucocele develop peritoneal pseudomixoma, possibly through
      dissemination of the epithelial cells into the abdominal cavity. Preoperative
      diagnosis of the lesion is particularly important in order to deal with it
      carefully during surgery. CT scan is the most precise radiological exploration,
      although there are no pathognomonic signs of mucocele. Typical CT finding of a
      mucocele is a well-defined cystic mass that compresses the cecum without any
      peripheral inflammatory reaction, and with low levels of attenuation that vary
      between water and soft tissue density. We present a case of an appendiceal
      mucocele caused by a mucinous cystadenoma clinically presented as a giant
      retroperitoneal mass. Diagnosis was postoperatively made, after pathological
      study of the surgical sample.

PMID- 15248409
TI  - [Enteroneovesical fistula].

PMID- 15248410
TI  - [New treatments for bronchial asthma].
AB  - Nowadays asthma treatment is based on topical beta2 short-acting and topical and
      systemic corticosteroids. Topical drugs do not control completely peripheral
      airways inflammation and also they are not able to control other disease
      frequently associated to asthma as rhinitis. Systemic steroids instead are very
      useful but not specific antinflammatory drug and can induce important side
      effects. For the reasons mentioned above it is important to use systemic drugs,
      acting on the numerous mediators typical of asthma, without modifying human
      physiological functions. We actually can use antileucotriens, but anti-IgE will
      be available also in Italy soon. Antileucotriens are effective and safe and are
      actually used in persistent asthma not completely controlled by inhaled steroids.
      They are administered per os; some of them are used once a day and can be used in
      paediatric age. In USA antileucotriens are also indicated in allergic rhinitis
      treatment. In atopic asthma, Omalizumab, an anti IgE drug, is safe and useful. It
      reduces the use of the systemic and inhaled steroids and the number of asthma
      exacerbations, in selected treated patients, without inducing important side
      effects. It is also useful in the treatment of rhinitis. Some proinflammatory
      cytochines, antiinflammatory cytochines and phosphodiesterasis inhibitor could be
      useful in the treatment of asthma but actually the use of these new drugs is
      still experimental.

PMID- 15248411
TI  - [Towards a pain-free hospital. Description of the campaign].
AB  - The various stages of the campaign "Towards a pain-free hospital", carried out at
      St. Bortolo Hospital in Vicenza, Italy, are described. They concerned: measuring
      pain prevalence, patients' beliefs, staff education, giving patients information,
      daily pain measurement, preparing pain treatment protocols, assessing patient
      satisfaction. The methods for carrying out the various initiatives and the data
      collected are reported.

PMID- 15248412
TI  - [Mental illness and media].
AB  - Many knowledges on the mental disease that the community possesses are turning
      out of information disclosed from the media. It's common in the press to connect
      actions of violence and murders to the mental diseases. For this reason, the
      reader is induced to infer that murders and other violent actions are more
      frequent in people who have suffered from mentally ill, than in the general
      population. The mystifying impression provided by media accrues from the fact
      that these reports are rarely compensated from positive reports. Objective of the
      present study is to characterize the type of information concerning mental
      illness diffused from the local daily paper "Giornale di Brescia" in the year
      2001. The results show that many articles connote negatively the mental disease.
      The journalistic sensationalism, denounced facing the speech of the prejudgment
      in the comparisons of the mentally ill people, seems to still remain, in the
      considered year of publication, one unchanging tendency.

PMID- 15248413
TI  - [Screening for thyroid disorders in elderly patients].
AB  - In elderly patients, thyroid diseases may remain undiagnosed due to the lack of
      specificity of the clinical presentation. Thyroid function alterations seem to be
      more common in older persons than in adults. The aim of our study was to evaluate
      the incidence of thyroid function alterations in 300 elderly patients admitted to
      the division of Internal Medicine of the local hospital in Levanto, in a one-year
      period. Thyroid function alterations were discovered in 12.6% of the patients and
      considering the group of patients in whom a thyroid function alteration was
      demonstrated, 45% of them were affected by hypothyroidism (10.7% overt primary
      hypothyroidism, 28.9% sub-clinical hypothyroidism, 5.4% hypothyroidism secondary
      to hypopituitarism), 15.6% by hyperthyroidism (overt 7.8% , subclinical 7.8%),
      and 39.4% showed a low T3 syndrome. Our data confirm the high incidence of
      previously unrecognized thyroid diseases in the elderly patients admitted to an
      hospital and the profit that these patients can receive from the appropriate
      diagnosis at the admission and justify the cost of routine testing for FT4 and
      TSH in every person at hospital admission.

PMID- 15248414
TI  - [No improvement of lipodystrophy syndrome in an HIV-infected patient].
AB  - Lipodystrophy in patients with HIV-infection has been studied intensively to
      understand its epidemiology and pathophysiology. Recently its development was
      attributed to a dysregulation of TNF-alpha synthesis' homeostasis by HAART. A few
      years ago it was found that pentoxifylline decreases TNF-alpha production. We
      describe one HIV-infected patient, with lipodystrophy syndrome, treated with
      pentoxifylline without any improvement of lipodystrophic symptoms.

PMID- 15248415
TI  - [Amoxicillin in tonsillectomy: preliminary data on the evaluation of serum and
      tissue concentrations].
AB  - Amoxicillin was administered to 50 patients with chronic recurrent tonsillitis
      waiting for tonsillectomy. Group A (N=16) received 2.2 g of amoxicillin plus
      clavulanic acid with intravenous injection 10 minutes before tonsillectomy Group
      B (N=34) was treated with 3 doses of amoxicillin-clavulanic acid administered
      orally the day before surgery, plus one oral administration 2 hours before
      tonsillectomy. Antibiotic doses were established on patient's weight using
      maximum suggested. The measures were, estimated in serum and in tonsils using
      High Performance Liquid Chromatography, (HPLC). The data show better efficacy of
      intravenous administration than oral administration.

PMID- 15248416
TI  - [Infections due to Legionella non-pneumophila].
AB  - Legionella species other than Legionella pneumophila may cause pneumonias and
      extrapulmonary infections. Most infections are nosocomial or observed in
      immunocompromised patients and often remain undiagnosed because of the failure of
      confirmatory culture methods. The therapy is based on macrolides and
      fluoroquinolones; rifampin and tetracycline are also used.

PMID- 15248417
TI  - [Borderline personality disorders in somatic illness].
AB  - The borderline personality disorders are very frequent in modern society because
      of cultural and social reasons. The authors analyze the disturbed mental
      processes (impulsiveness and memory) because they represent risk factors for the
      treatment of diseases. On the base of experience of consultation-liaison
      psychiatry, the authors show some guidelines in the medical practice (primary
      care and general hospital) in order to overcome the troubles of the treatment.

PMID- 15248418
TI  - [Urticaria and angioedema. An internal disorder with cutaneous manifestation].
AB  - Urticaria and angioedema will affect 15-20% of the general population during
      their lifetime, and this remains one of the most vexing conditions to evaluate
      and treat. This review of the literature is to give the reader a global insight
      into the spectrum of urticaria and angioedema, focusing on differential diagnosis
      and pathogenic mechanisms. It will define the role of the mast cell, exploring a
      possible autoimmune basis for urticaria. Last, the different potential treatments
      will be discussed. Urticaria and angioedema are frustrating problems for both
      physicians and their patients; however, the problem may best be approached by
      considering urticaria as a general affection rather than a specific cutaneous
      disease. The physical examination and medical history remain the two most
      important pieces of information.

PMID- 15248419
TI  - [The medical intuitions of Charles Dickens, creator of people and worlds].

PMID- 15248420
TI  - [Subclinical thyroid disorders. Guidelines of the American Thyroid Association].

PMID- 15248421
TI  - Comparison of different extraction methods: steam distillation, simultaneous
      distillation and extraction and headspace co-distillation, used for the analysis
      of the volatile components in aged flue-cured tobacco leaves.
AB  - Steam distillation (SD), simultaneous distillation and extraction (SDE) and
      headspace co-distillation (HCD) were compared here for their effectiveness in the
      extraction of volatile compounds from tobacco. The different grades of aged flue
      cured tobacco leaves extracted by the three methods respectively were analyzed
      using GC-MS. Mass spectra or authentic compounds were used to identify around 408
      components in various volatile fractions. On the one hand, the qualitative
      comparison showed that more compounds were detected in HCD extract (391
      components) than in SDE extract (377 components), and the approximately
      quantitative analysis showed that the total amount of volatile components in SDE
      extract (445.48 microg/g) was much more than that in HCD extract (315.72
      microg/g). But on the other hand, HCD was the most efficient for nearly all the
      highly volatile compounds among the three methods. As to low-volatile compounds
      such as lactones, long chain aldehydes, ketones, alcohols, and esters, more was
      detected in SDE extract than in HCD extract. The SD method (322 components, total
      amount 228.42 microg/g) was the lowest sensitive to all compounds except semi
      volatile fatty acids among the three methods.

PMID- 15248422
TI  - Recursion equations in predicting band width under gradient elution.
AB  - The evolution of solute zone under gradient elution is a typical problem of non
      linear continuity equation since the local diffusion coefficient and local
      migration velocity of the mass cells of solute zones are the functions of
      position and time due to space- and time-variable mobile phase composition. In
      this paper, based on the mesoscopic approaches (Lagrangian description, the
      continuity theory and the local equilibrium assumption), the evolution of solute
      zones in space- and time-dependent fields is described by the iterative addition
      of local probability density of the mass cells of solute zones. Furthermore, on
      macroscopic levels, the recursion equations have been proposed to simulate zone
      migration and spreading in reversed-phase high-performance liquid chromatography
      (RP-HPLC) through directly relating local retention factor and local diffusion
      coefficient to local mobile phase concentration. This new approach differs
      entirely from the traditional theories on plate concept with Eulerian
      description, since band width recursion equation is actually the accumulation of
      local diffusion coefficients of solute zones to discrete-time slices. Recursion
      equations and literature equations were used in dealing with same experimental
      data in RP-HPLC, and the comparison results show that the recursion equations can
      accurately predict band width under gradient elution.

PMID- 15248423
TI  - Extra-column dispersion of macromolecular solutes in aqueous-phase size-exclusion
      chromatography.
AB  - A set of dextran standards was used to study the extra-column dispersion in
      conventional chromatographic equipment at a broad range of molecular weights,
      different mobile phase flow rates and connecting tube lengths and diameters. All
      known correlations for the tube dispersion at laminar flow, including those for
      short tubes, overestimated the values of the variance of the outlet concentration
      signal. The difference increased with the solute molecular weight and the flow
      rate. It was assumed that the discrepancy was due to the effect of natural
      convection invoked by the density differences of the injected dextran solutions
      and water. A suitable approximation of the relative band spreading was suggested
      in a form of a power function of the Reynolds and Schmidt numbers. A significant
      decrease of the dispersion was observed when the chromatography tubing was coiled
      into a circle. This decrease was successfully predicted combining the existing
      correlations for long coiled tubes and short straight tubes.

PMID- 15248424
TI  - Solute retention and the states of water in polyethylene glycol and poly(vinyl
      alcohol) gels.
AB  - The states of water sorbed in a cross-linked polyethylene glycol (PEG) gel,
      TSKgel Ether-250, and cross-linked poly(vinyl alcohol) (PVA) gels of different
      pore sizes, TSKgel Toyopearl HW-40S, 50S, 55S and 75S, were investigated by means
      of differential scanning calorimetry (DSC). It was found that there were three
      types of water in these hydrogels, non-freezing water, freezable bound water and
      free water. The amount of water that functions as the stationary phase in the
      column packed with the each gel was also estimated by a liquid chromatographic
      method. The estimated amount of the stationary phase water is in good agreement
      with the sum of the amount of non-freezing water and that of freezable bound
      water for HW-40S, 50S and 55S, while it agrees with the amount of only non
      freezing water for HW-75S and Ether-250. This means that the stationary phase
      water consists of non-freezing water and freezable bound water for HW-40S, 50S
      and 55S, while only non-freezing water functions as the stationary phase in HW
      75S and Ether-250 gels. This result can be attributed to the difference in the
      structure of the gels; the PVA gels containing PVA at relatively high
      concentrations, HW-40S, 50S and 55S, have a homogeneous gel phase, whereas HW-75S
      and Ether-250 have a heterogeneous gel phase consisting hydrated polymer domains
      and macropores with relatively hydrophobic surface. The freezable bound water in
      Toyopearl HW-40S, 50S and 55S can be regarded as a component of a homogeneous PVA
      solution phase, while that in HW-75S and Ether-250 may be water isolated in small
      pores of the hydrophobic domains. The results obtained by the investigation on
      the retention selectivity of these hydrogels in aqueous solutions supported our
      postulated view on the structures of the hydrogels.

PMID- 15248425
TI  - Preparation and characterization of a p-tert-butyl-calix[6]-1,4-benzocrown-4
      bonded silica gel stationary phase for liquid chromatography.
AB  - A p-tert-butyl-calix[6]-1,4-benzocrown-4-bonded silica gel stationary phase
      (CR6BS) was first prepared via 3-glycidoxypropyltrimethoxysilane as coupling
      reagent for high performance liquid chromatography. The structure of the new
      stationary phase was characterized by diffuse reflectance infrared fourier
      transform spectroscopy (DRIFT), elemental analysis and thermal analysis. The
      chromatographic performance of the bonded-stationary phase was evaluated by using
      neutral, acidic and basic solutes as probes. Meanwhile, comparative study of the
      new stationary phase with a p-tert-butyl-calix[6]arene-bonded silica gel
      stationary phase (C6BS, the parent) and ODS was done under the same
      chromatographic conditions. The results show that the new stationary phase has an
      excellent reversed-phase property, which is similar to C6BS and ODS. However, the
      selectivities for some aromatic compounds are different from the parent phase
      (C6BS) and ODS, especially the latter. In one hand, as hybrid of calixarene and
      crown ether, CR6BS with the oxygen atoms of ether-bridge can provide the
      complexation sites for the solutes, lacking of C6BS. On the other hand, the rigid
      conformation of CR6BS may be responsible to the different performance partially.
      CR6BS exhibits high selectivity in the separation of alkylated aromatics from
      their parents as compared with C6BS.

PMID- 15248426
TI  - Countercurrent chromatographic separation: a hydrodynamic approach developed for
      extraction columns.
AB  - In countercurrent chromatography (CCC) both stationary and mobile liquids undergo
      intense mixing in the variable force field of a coil planet centrifuge and the
      separation process, like the separation in conventional solvent extraction
      column, is influenced by longitudinal mixing in the phases and mass transfer
      between them. This paper describes how the residence time distribution (or the
      elution profile) of a solute in CCC devices and the interpretation of
      experimental peaks, can be described by a recently developed cell model of
      longitudinal mixing. The model considers a CCC column as a cascade of perfectly
      mixed equal-size cells, the number of which is determined by the rates of
      longitudinal mixing in the stationary and mobile phases. Experiments were carried
      out to demonstrate the validation of the model and the possibility of predicting
      the partitioning behaviour of the solutes. The methods for estimating model
      parameters are discussed. Longitudinal mixing rates in stationary and mobile
      phases have been experimentally determined and experimental elution profiles are
      compared with simulated peaks. It is shown that using the cell model the peak
      shape for a solute with a given distribution constant can be predicted from
      experimental data on other solutes.

PMID- 15248427
TI  - Separation and identification of the light harvesting proteins contained in grana
      and stroma thylakoid membrane fractions.
AB  - This paper presents the results of a study performed to develop a rapid and
      straightforward method to resolve and simultaneously identify the light
      harvesting proteins of photosystem I (LHCI) and photosystem II (LHCII) present in
      the grana and stroma of the thylakoid membranes of higher plants. These
      hydrophobic proteins are embedded in the phospholipid membrane, and their
      extraction usually requires detergent and time consuming manipulations that may
      introduce artifacts. The method presented here makes use of digitonin, a
      detergent which causes rapid (within less than 3 min) cleavage of the thylakoid
      membrane into two subfractions: appressed (grana) and non-appressed (stroma)
      membranes, the former enriched in photosystem II and the latter containing mainly
      photosystem I. From these two fractions identification of the protein components
      was performed by separating them by reversed-phase high-performance liquid
      chromatography (RP-HPLC) and determining the intact molecular mass by
      electrospray ionization mass spectrometry (ESI-MS). By this strategy the ion
      suppression during ESI-MS that normally occurs in the presence of membrane
      phospholipids was avoided, since RP-HPLC removed most phospholipids from the
      analytes. Consequently, high quality mass spectra were extracted from the
      reconstructed ion chromatograms. The specific cleavage of thylakoid membranes by
      digitonin, as well as the rapid identification and quantification of the antenna
      composition of the two complexes facilitate future studies of the lateral
      migration of the chlorophyll-protein complexes along thylakoid membranes, which
      is well known to be induced by high intensity light or other environmental
      stresses. Such investigations could not be performed by sodium dodecylsulfate
      polyacrylamide gel electrophoresis because of insufficient resolution of the
      proteins having molecular masses between 22,000 and 25,000.

PMID- 15248428
TI  - Identification of iso- and n-propylphosphonates using liquid chromatography
      tandem mass spectrometry and gas chromatography-Fourier transform infrared
      spectroscopy.
AB  - Organophosphorus nerve agents and their precursors, specifically listed in the
      schedules of chemicals in the Annex to the Chemical Weapons Convention (CWC),
      include analogues with C1-C3 alkyl groups on phosphorus. The Organisation for the
      Prohibition of Chemical Weapons (OPCW) requires designated laboratories to
      unequivocally identify isomeric propyl groups bonded to phosphorus in analytes
      that may be present in samples submitted for analysis. Homologous series of
      isomeric pairs of dialkyl iso- and n-propylphosphonates, alkyl iso- and n
      propylphosphonochloridates, and alkyl iso- and n-propylphosphonofluoridates, have
      been analysed by liquid chromatography-ion trap tandem mass spectrometry and/or
      by gas chromatography-Fourier transform infrared spectroscopy. The results show
      that P-propyl isomers can be reliably differentiated by collision induced
      dissociation (CID) of selected fragment ions and by their infrared P=O stretching
      and C-H deformation frequencies.

PMID- 15248429
TI  - Laser-induced breakdown detection combined with asymmetrical flow field-flow
      fractionation: application to iron oxi/hydroxide colloid characterization.
AB  - The combination of asymmetrical flow field-flow fractionation (AsFlFFF) with the
      laser-induced breakdown detection (LIBD) is presented as a powerful tool for the
      determination of colloid size distribution at trace particle concentrations.
      Detection limits (D1) of 1, 4, and 20 microg/L have been determined for a mixture
      of polystyrene reference particles with 20, 50, and 100 nm in size, respectively.
      This corresponds to injected masses of 1, 4, and 20 pg, which is lower than found
      in a previous study with the symmetrical FlFFF (SyFlFFF). The improvement is
      mainly due to the lower colloid background discharged from the AsFlFFF channel.
      The combined method of AsFlFFF-LIBD is then applied to the analysis of iron
      oxi/hydroxide colloids being considered as potential carriers for the
      radionuclide migration from a nuclear waste repository. Our LIBD arrangement is
      less sensitive for iron colloid detection as compared to reference polystyrene
      particles which results in a detection limit of approximately 240 microg/L FeOOH
      for the AsFlFFF-LIBD analysis. This is superior to the detection via UV-Vis
      absorbance and comparable to ICP-MS detection. Size information (mean size 11-18
      nm) for different iron oxi/hydroxide colloids supplied by the present method is
      comparable to that obtained by sequential ultrafiltration and dynamic light
      scattering. A combined on-line ICP-MS detection is used to gain insight into the
      colloid-borne main and trace elements.

PMID- 15248430
TI  - Analysis of heterocyclic aromatic amines in foods by gas chromatography-mass
      spectrometry as their tert.-butyldimethylsilyl derivatives.
AB  - A derivatization method for the analysis of 12 heterocyclic aromatic amines (HAs)
      in food, by gas chromatography-electron impact mass spectrometry, was developed.
      The amines are derivatized in a one-step reaction with N-methyl-N-(tert.
      butyldimethylsilyl)trifluoroacetamide. The derivatives are characterized by easy
      to-interpret mass spectra due to the prominent ion [M-57]+ by loss of a tert.
      butyldimethylsilyl group, allowing quantification in the selected-ion monitoring
      mode at the picogram level. The effect of temperature, time, and reagents on the
      formation of the derivatives was monitored in detail. Quality parameters were
      evaluated in the optimum working conditions. This derivatization method is not
      applicable to the pyridoimidazoles Glu-P-1 and Glu-P-2 and to the beta-carboline
      harman due to incompletely derivatization. The instability of the
      imidazolquinoline and imidazoquinoxaline derivatives, requiring their injection
      on the same working day, is a further drawback. This simple, rapid and accurate
      derivatization procedure is suitable for routine analysis, as illustrated by the
      analysis of some common foods.

PMID- 15248431
TI  - Glycolipid class profiling by packed-column subcritical fluid chromatography.
AB  - The potential of packed-column subcritical fluid chromatography (SubFC) for the
      separation of lipid classes has been assessed in this study. Three polar
      stationary phases were checked: silica, diol, and poly(vinyl alcohol). Carbon
      dioxide (CO2) with methanol as modifier was used as mobile phase and detection
      performed by evaporative light scattering detection. The influence of methanol
      content, temperature, and pressure on the chromatographic behavior of
      sphingolipids and glycolipids were investigated. A complete separation of lipid
      classes from a crude wheat lipid extract was achieved using a modifier gradient
      from 10 to 40% methanol in carbon dioxide. Solute selectivity was improved using
      coupled silica and diol columns in series. Because the variation of eluotropic
      strength depending on the fluid density changes, a normalized separation factor
      product (NSP) was used to select the nature, the number and the order of the
      columns to reach the optimum glycolipid separation.

PMID- 15248432
TI  - Analysis of anabolic steroids by partial filling micellar electrokinetic
      capillary chromatography and electrospray mass spectrometry.
AB  - A partial filling micellar electrokinetic capillary chromatography (PF-MEKC)
      separation of six anabolic androgenic steroids (androstenedione, metandienone,
      fluoxymesterone, methyltestosterone, 17-epimetandienone and testosterone) is
      introduced. The method utilises a mixed micellar solution consisting of sodium
      dodecyl sulphate (SDS) and sodium taurocholate. The analytes are detected with a
      photodiode array detector at 247 nm wavelength. Methyltestosterone is used as
      internal standard. The detection limits were 39 microg/L for androstenedione, 40
      microg/L for testosterone, 45 microg/L for fluoxymesterone, 45-90 microg/L for 17
      epimetandienone, 59 microg/L for methyltestosterone and 90 microg/L for
      metandienone. Linear correlation between concentration (0.1-5.0 mg/L) and
      detector response was obtained with r2 of 0.994 for fluoxymesterone, 0.998 for 17
      epimetandienone and 0.999 for androstenedione, metandienone and testosterone. In
      addition, ionisation of the investigated compounds in electrospray mass
      spectrometry (ESI-MS) was studied in positive ion mode. The most intense signal
      (100%) was the protonated molecular ion [M + H]+, except for 17-epimetandienone,
      which gave its strongest signal at m/z corresponding to [M - H2O + H]+. Finally,
      separation and identification of fluoxymesterone, androstenedione and
      testosterone by PF-MEKC-ESI-MS is described. This is the first use of PF-MEKC and
      PF-MEKC-ESI-MS assays for anabolic androgenic steroids.

PMID- 15248433
TI  - Determination of histamine and histidine by capillary zone electrophoresis with
      pre-column naphthalene-2,3-dicarboxaldehyde derivatization and fluorescence
      detection.
AB  - A rapid and sensitive method was developed for the simultaneous determination of
      histamine and histidine by capillary zone electrophoresis with lamp-induced
      fluorescence detection. A fluoregenic derivatization reagent, naphthalene-2,3
      dicarboxaldehyde (NDA) was successfully applied to label the histamine and
      histidine respectively. The derivatization conditions and separation parameters
      including pH and concentration of electrolyte and sample injection were optimized
      in detail. The optimal derivatization reaction was performed with 1.0 mM NDA, 20
      mM NaCN, and 20 mM borate buffer, pH 9.1 for 15 min. The separation of NDA-tagged
      histamine and histidine could be achieved in less than 200 s with 40 mM phosphate
      buffer (pH 5.8) as the running buffer. The detection limits for histamine and
      histidine were 5.5 x 10(-9) and 3.8 x 10(-9) M, respectively (S/N = 3). The
      relative standard derivations for migration time and peak height of derivatives
      were less than 1.5 and 5.0%, respectively. The method was successfully applied to
      the analysis of histamine and histidine in the P815 mastocytoma cells and the
      beer samples.

PMID- 15248434
TI  - Capillary electrophoretic studies of acid-base properties of sanguinarine and
      chelerythrine alkaloids.
AB  - Capillary zone electrophoresis with UV detection was used for determination of
      dissociation constants of alkaloids sanguinarine and chelerythrine. Despite the
      limited solubility of the uncharged forms of the alkaloids resulting in
      insufficient analytical signal at higher pH the reliable dissociation constants
      were obtained when acidified samples containing low amount of the alkaloid were
      injected into the capillary. The precipitation of the alkaloid in the capillary
      induced by injecting sample of low pH into the background electrolyte of higher
      pH does not affect the mobility of the alkaloid if its concentration injected
      exceeds the solubility only to a small extent. Dissociation constants (pK(R+)) of
      sanguinarine and chelerythrine calculated to 8.3 +/- 0.1 and 9.2 +/- 0.1,
      respectively, are relevant to Good buffers of ionic strength of 30 mM.

PMID- 15248435
TI  - Preparative separation of flavonoid glycosides in leaves extract of Ampelopsis
      grossedentata using high-speed counter-current chromatography.
AB  - Preparative separation of flavonoid glycosides in leaves extract of Ampelopsis
      grossedentata was conducted using high-speed counter-current chromatograph
      (HSCCC) with a solvent system composed of n-hexane-ethyl acetate-methanol-water
      (1:6:1.5:7.5, v/v). In a single operation, 28 mg of 5,7-dihydroxy-3',4'
      trihydroxyflavone-3-O-6''-rhamnose and 18 mg of 5,7-dihydroxy-3',4'
      dihydroxyflavone-3-O-6''-rhamnose was obtained from 150 mg of the extract. The
      chemical structure of the two compounds was elucidated by electrospray ionization
      (EIS) MS and NMR.

PMID- 15248436
TI  - Preparation of an iminodiacetic acid-modified capillary and its performance in
      capillary liquid chromatography and immobilized metal chelate affinity capillary
      electrophoresis.
AB  - We prepared iminodiacetic acid (IDA)-modified and Cu(II)-IDA-modified capillaries
      through polymerization of N-(vinylbenzylimino) diacetic acid. The fundamental
      performance of these capillaries was examined in capillary liquid chromatography
      (LC) and immobilized metal chelate affinity capillary electrophoresis (IMACE).
      Copper(II), cobalt(II), and hematin were detected at different retention times by
      means of capillary LC with a chemiluminescence detector, during which the IDA
      modified capillary was used. The difference in the retention times was attributed
      to the difference in the interaction between metal ions or complex and IDA
      moieties on the inner wall of the capillary. In addition, human serum albumin
      (HSA) and human serum gamma-globulin (HgammaG) were separated and detected using
      IMACE with an absorption detector, during which the Cu(II)-IDA-modified capillary
      was used. The separation of HSA and HgammaG was achieved through the interaction
      between proteins and Cu(II) chelate moieties on the inner wall of this capillary.

PMID- 15248437
TI  - [Peripheral pulmonary embolism: the Achille's heel of the D-dimers?].

PMID- 15248438
TI  - [Negative D-dimers and peripheral pulmonary embolism].
AB  - The measurement of D-dimers is a recent addition to the diagnostic strategy of
      pulmonary embolism and has been shown to be a valuable tool with excellent
      sensitivity. However, there have been rare reports of patients with pulmonary
      embolism but negative D-dimer tests. The object of this study was to study
      patients with pulmonary embolism but negative D-dimers and to compare them with a
      population of patients with pulmonary embolism and raised D-dimers. One hundred
      and fifty consecutive patients admitted for pulmonary embolism were included in
      this study. All underwent measurement of D-dimers (normal <500 ng/ml) by an ELISA
      technique. The data of clinical examination and complementary investigations were
      analysed with respect to the D-dimers result. The sensitivity of raised D-dimers
      for pulmonary embolism was 96% (6 patients had results <500 ng/ml). The finding
      of chest pain was statistically greater in the group with negative D-dimers
      (p=0.01). In these cases, the emboli were all distal (p=0.0003), the average
      Miller index was significantly lower than in patients with high D-dimers (p=0.04)
      and the diagnostic value of ultrasound investigations (echocardiography,
      ultrasonography of lower limb veins) was less (p<0.0001). The authors conclude
      that measurement of D-dimers by the ELISA method may be non-diagnostic in distal
      pulmonary embolism and one explanation could be the less extensive thromboembolic
      process. In cases with negative D-dimers, a strong clinical suspicion of
      pulmonary embolism should lead to the request for further investigations.

PMID- 15248439
TI  - [Complete revascularisation of multivessel coronary artery disease during acute
      myocardial infarction. Results following hospitalization and after 30 months.
      Series of 86 interventions carried out with 167 multivessel disease patients;
      causes of failure].
AB  - This series studied 167 patients with multivessel disease, admitted consecutively
      for acute myocardial infarction (excluding cardiogenic shock), who underwent
      systematic angioplasty and stenting before the 12th hour of the culprit artery
      and the other vessels with >70% (QCA) angiographic stenosis, and followed up for
      a period of 8 to 68 months with an average follow-up of 2.5 years. The criteria
      of evaluation were: numbers of asymptomatic patients, deaths, new infarctions,
      residual ischaemias, cardiac failure, angioplasties or bypass surgeries. On
      admission, 43.1% of infarcts were anterior, 48.5% inferior or postero-inferior
      and 8.3% lateral wall infarcts. One hundred and twenty-two consecutive patients
      had double vessel disease and 45 has triple vessel disease. The failures of
      revascularisation of the culprit artery were excluded from the study. The
      feasibility rate of complete multivessel revascularisation in a single procedure
      was over half the cases (86 out of 167, 51.5%): 60.6% of double vessel disease
      and 26.9% of triple vessel disease, a simple favorable anatomical presentation
      being necessary to accomplish this objective. During the hospital period (30
      days), 95.3% of patients who were completely revascularised remained totally
      asymptomatic, 2 (2.3%) had recurrent infarction, 1 (1%) had cardiac failure and 1
      (1%) died of a non-cardiac cause. No cardiac deaths were observed in this series.
      Of the multivessel disease patients who could not be completely revascularised
      (N=81) (poor clinical state or complicated anatomical presentation), 83.6% were
      asymptomatic: there were 7.7% cases of cardiac failure, 2.4% of recurrent
      infarction; 1.2% died of non-cardiac causes and 1.2% died of a cardiac cause. The
      statistical difference was significant in favour of the patients who had
      successful complete revascularisation with respect to the others in terms of
      numbers of asymptomatic patients (p=0.004) and of numbers of cardiac failure
      (p=0.002). The follow-up rate of patients who had complete revascularisation in a
      single procedure was 98.8%. After two and a half years of follow-up, 74.1% of
      patients were totally asymptomatic; the cumulative major cardiac adverse event
      rate (death, infarction, angioplasty or bypass surgery) was 29.4% and the
      reoperation rate by angioplasty or bypass surgery was 27%.

PMID- 15248440
TI  - [Absence of nephro-protective effect of acetylcysteine in patients with chronic
      renal failure investigated by coronary angiography].
AB  - Recent studies have suggested that an oral dose of acetylcysteine could play a
      prophylactic role in the prevention of nephrotoxicity from iodine contrast media
      in patients affected by chronic renal failure. Between June 2001 and September
      2002 we selected 120 patients with a basal plasma creatinine level greater than
      1.36 mg/dl investigated by coronary angiography. The treatment group included 60
      patients who received 600 mg of acetylcysteine in the morning and evening before
      the day of the examination together with intravenous saline hydration. The
      control group patients received hydration alone. The clinical characteristics of
      the groups were comparable as well as the basal plasma creatinine level: 2.01+/
      1.1 mg/dl in the acetylcysteine group and 1.81+/-0.69 in the control group. The
      plasma creatinine level was measured 24 and 48 hours after coronary angiography.
      The respective changes in plasma creatinine level at 24 and 48 hours were 0.12+/
      0.29 and 0.02+/-0.29 mg/dl in the acetylcysteine group and 0.06+/-0.29 and 0.07+/
      0.43 mg/dl in the control group (NS). Acute renal failure caused by the contrast
      medium, defined by an increase of 25% in the plasma creatinine level compared to
      the basal value, occurred in 3 patients from the acetylcysteine group and 2
      patients from the control group. The only predictive factor for acute renal
      failure was the quantity of contrast medium (316+/-141 vs 173+/-115 ml, p<0.05).
      In conclusion, acute renal failure caused by contrast medium is rare in
      sufficiently hydrated patients with moderate chronic renal failure when a low
      dose of contrast medium is used. Our study does not confirm a prophylactic effect
      of acetylcysteine in the prevention of nephrotoxicity from contrast media
      following coronary angiography in patients with moderate chronic renal failure.

PMID- 15248441
TI  - [Atrial lead placement in the right atrial appendage during recent or chronic
      arrhythmia].
AB  - An atrial arrhythmia could be encountered during the atrial lead implantation.
      The lead placement must subsequently be delayed after restitution of the sinus
      rhythm or completely abandoned. The authors investigate the atrial lead placement
      during atrial arrhythmia and the lead performance at 6-month follow-up. The study
      population was 65 patients aged 78.5 years, 42 males and 28 structural heart
      diseases. They were implanted for sick sinus syndrome (n=14), atrioventricular
      block (n=44), infra-hisian conduction abnormality (n=7) in association with an
      atrial fibrillation (63.1%), an atrial flutter (24.6%) or an atrial tachycardia
      (12.3%). The onset of the arrhythmia was < or = 7 days (47.7%) or > 7 days
      (52.3%). An atrial lead was placed in the right atrial appendage under
      fluoroscopic control. If the sinus rhythm was not restored at 1 month, an
      electrical cardioversion was performed. The per-implantation atrial signal
      amplitude was 2.2+/-1.5 mV (range 0.5 mV to 7 mV). Sinus rhythm was restored in
      54 patients. At 1 month, one patient was in an incessant atrial fibrillation. The
      53 patients in sinus rhythm had a good atrial lead performance. Out of 46
      patients who completed the 6-month follow-up, 4 had an arrhythmia recurrence. The
      42 patients in sinus rhythm had a good atrial lead performance. At 1 and 6-month
      follow-up, the atrial pacing threshold (1.1+/-0.7 V vs 1.2+/-1.0 V, ns) and the
      atrial signal amplitude (2.1+/-1.0 mV and 2.1+/-0.9 mV, ns) were stable.
      Comparing the patients with a recent or a chronic arrhythmia, the pacing
      thresholds (1.2+/-1.1 V vs 1.14+/-0.8 V, ns), the atrial signal amplitudes
      (2.17+/-0.9 mV vs 2.05+/-0.9 mV, ns) and the proportion of satisfactory pacemaker
      performance in DDD(R) mode for the patients in sinus rhythm (100% vs 100%, ns)
      did not statistically differ between the two groups at 6 months. In conclusion,
      the placement of an atrial lead in the right atrial appendage during an atrial
      arrhythmia is feasible with a good lead performance at 6 months in sinus rhythm
      regardless the onset time of the arrhythmia and provides a satisfactory atrial
      based pacing with the preservation of the atrioventricular synchrony.

PMID- 15248442
TI  - [Predictive criteria of early recurrence of atrial arrhythmia after reduction by
      electrical cardioversion].
AB  - The management of atrial arrhythmias aims not only to restore sinus rhythm but
      also to maintain it. Ten to thirty per cent of patients have early recurrence of
      atrial arrhythmias, the treatment of which remains empiric. The aim of this study
      was to define factors predictive of early recurrence of atrial arrhythmias and
      the consequences on the length of hospital stay. A series of 131 patients who
      underwent reduction of atrial arrhythmias by electrical cardioversion was studied
      retrospectively. A recurrence within 24 hours was observed in 12.2% of the
      patients. These recurrences significantly increased the length of hospital stay
      (6.8+/-6.3 versus 3.6+/-3.8 days, p=0.005). This study confirms two previously
      reported results with respect to more long-term recurrences. In the "early
      recurrence" group, the duration of the atrial arrhythmia was longer (p=0.003) and
      there were fewer treatments with amiodarone (p=0.03). In addition, original
      results were obtained. In the "early recurrence" group, the patients were more
      often treated with furosemide (p=0.02), class Ic antiarrhythmics (p=0.007) or
      anaesthetised with thiopental (p=0.002) than patients without early recurrences.
      Experimental data explain these results. However, they require confirmation by a
      prospective randomised trial.

PMID- 15248443
TI  - [Measurement of the mitral area with three-dimensional cardiac echography].
AB  - Two dimensional planimetry of mitral stenosis is sometimes difficult due to the
      complex morphology of the mitral valve. Three dimensional cardiac echography
      images the projected area of the mitral valve allowing precise planimetry of the
      orifice. Thirty patients with mitral stenosis were included in this study in
      order to obtain planimetry of the mitral orifice with two dimensional and three
      dimensional "freehand" mode transthoracic echocardiography. In 10 patients, the
      measurements were taken before and after percutaneous commissurotomy. The mitral
      area measured with three dimensional echography was 1.36+/-0.45 cm2 and 1.39+/
      0.43 cm2 in two dimensional mode. The correlation between the 2 methods was good
      (y=1.01x - 0.08, r=0.92, p<0.001) but three dimensional echocardiography
      significantly underestimated the two dimensional planimetry by 0.05+/-0.27 cm2
      (4+/-20%, p<0.05). The intra- and inter-observer reproducibility of the three
      dimensional measurements were 0.95 and 0.91 respectively. Three dimensional free
      hand mode cardiac echography allows precise measurement of the mitral orifice
      area in patients with mitral stenosis.

PMID- 15248444
TI  - [Risk factors for cardiac mortality in cases of syncope with previous history of
      myocardial infarction].
AB  - Syncope is considered to be a clinical sign predictive of sudden death in
      patients with a previous history of myocardial infarction. The aim of this study
      was to determine the prognostic factors in this population. The study population
      included 228 patients with myocardial infarction over one month old and who had
      no documented ventricular tachycardia. The patients were referred for
      investigation of syncope. The left ventricular ejection fraction (LVEF) was
      measured by echocardiography or radionucleide technique. Complete
      electrophysiological study including programmed atrial and ventricular
      stimulation was performed in all cases. The patients were followed up for 6
      months to 5 years or until cardiac transplantation (average 3+/-1 years). One
      hundred and nineteen patients had a LVEF <40% (Group I) and 109 patients had a
      LVEF >40% (Group II). Sustained monomorphic ventricular tachycardia (VT) with a
      rate inferior to 280/min was induced in 44 patients in Group I (37%) and in 18
      patients in Group II (16.5%), p<0.05. Ventricular flutter or fibrillation was
      induced in 24 patients in Group I (19%) and in 19 patients in Group II (17%)
      (NS). Different causes of syncope (conduction disturbances, supraventricular
      tachycardia, increased vagal tone, severe coronary ischaemia) were found in 23
      patients in Group I (19%) and 32 patients in Group II (29%) (NS). Syncope was
      unexplained in 43 patients in Group I (36%) and 40 patients in Group II (37%)
      (NS). The prognosis was very different. In Group I, the cardiac mortality was 49%
      in patients with inducible monomorphic VT <280/min, 35% in those with inducible
      ventricular flutter or fibrillation but only 9% in patients without inducible
      ventricular arrhythmias. In Group II, the prognosis was independent of the
      results of programmed stimulation and much better: cardiac mortality was 5.5% in
      patients with inducible VT, 5% in those with inducible ventricular flutter or
      fibrillation and 4% in patients without inducible ventricular arrhyhtmias. The
      authors conclude that LVEF is the most powerful predictor of cardiac mortality
      and sudden death in cases of syncope with a past history of myocardial
      infarction. The prognosis also depends on the results of programmed ventricular
      stimulation when the LVEF is inferior to 40%. Sustained monomorphic VT is the
      most frequently induced arrhythmia in this case and the prognosis of these
      patients is particularly poor. On the other hand, syncope does not appear to be a
      poor prognostic factor in the group with normal LVEF, even when it is possible to
      induce VT.

PMID- 15248445
TI  - [Has the obligation to inform patients changed our mode of practice?].
AB  - From January 2000, the Council of State has harmonised the jurisprudence with the
      Court of Appeal, changing the responsibility of medical practitioners by
      requiring them to provide proof that information was both given and understood by
      their patients. This obligation to inform patients raises several questions: who
      should give the information? to whom should the information be addressed? how can
      proof of this information be provided? what should the information be? The
      authors sent a questionnaire to practicing cardiologists by the internet site of
      the French Society of Cardiology from the 1st December 2002 to 15th January 2003.
      Three hundred and thirty-two replies were received of which 305 could be
      exploited. The activities of the cardiologists who replied were mainly in public
      hospitals (51.8%), private (18.2%) or mixed (30%). Patient information was mainly
      performed before invasive procedures, especially coronary angiography (90%) or
      cardiac pacing (77.3%). On the other hand, it was less commonly undertaken before
      exercise stress tests (63.2%) or transoesophageal echocardiography (61.4%),
      although these percentages are much higher than those recorded during previous
      enquiries in 2000 and 2001. The information given was, in the large majority of
      cases, that proposed by the French Society of Cardiology and it was usually the
      practitioner who ordered the investigation who informed the patient (45.4%). In
      2002, the role of the nurse was much greater as the nurse informed the patient in
      27.2% of cases. The patient was generally given the information the day before
      the procedure was carried out (74.1%) with complementary information (90.7%), and
      less than 1% of patients declined the investigation under these conditions. In
      order to provide proof of patient information, the practitioner usually required
      the patient's signature (58.3% of cases); less commonly, the referring physician
      was informed by letter (13.9% of cases) or a note was made in the patient's file
      (33.9% of cases). The new requirements for patient information have changed
      medical practice in nearly 53.5% of cases. Finally, although patient information
      is considered to be part of the normal patient-doctor relationship in most cases
      (42.7%), doctors thought that patients interpreted this procedure as a cover for
      the medical team in 18.2% of cases. The information bases most commonly used to
      determine the methods of informing patients and the nature of the information to
      be provided were medical reviews (38.9%) or the internet (30.5%). The authors
      conclude that patient information is carried out before complementary
      cardiological investigations. The new laws of the Code of Public Health are not
      well known. Finally, the proof of patient information is not easily provided and
      the majority of cardiologists request written patient consent, which is not a
      legal requirement.

PMID- 15248446
TI  - [Impact of biochemisty on the duration of treatment for pulmonary embolus].
AB  - Can the biochemical evidence for "new thrombophilic factors" influence the
      duration of AVK treatment following the occurrence of a first pulmonary embolus?
      Certainly for the classic but very rare antithrombin defects as well as for the
      existence of circulating anticoagulant. Possibly for protein C and S defects. On
      the other hand, the existence of a heterozygotic "Leiden" mutation of factor V,
      or factor II, and an increase of factors VIII, IX, or XI, do not at present
      warrant a change in AVK prescription. In effect, in the case where the existence
      of a thrombogenic state implies a prolongation of AVK treatment with its
      significant potential complications, it is indispensable that the risk/benefit
      ratio is well founded, which is not the case for these "new" thrombophilic
      states. The coexistence of several of these new biochemical anomalies (for
      example the association of a factor V and factor II mutation) probably represents
      an excess risk of thrombosis, but in this situation the reasoning remains the
      same. On the other hand, faced with a confirmed recurrence, the studies in the
      literature tell us that very long term treatment should be debated independently
      from the biochemical results. It is conceivable that there are biochemical
      anomalies (sometimes quite frequent which should be viewed as "normal variants")
      which, although they have great significance for improving the understanding of
      venous thrombo-embolic disease, do not at present warrant a change in our
      therapeutic protocols. Another facet of the problem concerns the use of D-dimers
      following the first months of AVK treatment in order to possibly distinguish
      patients at low risk of recurrence. The first results of this approach are
      interesting, but require confirmation before they can be used in practice.

PMID- 15248447
TI  - [Portable echocardiographs: useful or futile?].
AB  - Echocardiographic systems which are the size of a laptop computer are currently
      available. These hand-held ultrasound units are very easy to use at patient
      bedside in various clinical settings. According to the miniaturized devices,
      spectral Doppler may not be available and power Doppler may replace true color
      Doppler. Validation studies of hand-held echocardiography have been conducted in
      critically ill patients, in patients hospitalized in ward, but also in
      outpatients and as a screening tool for the detection of cardiac abnormalities in
      the community. Hand-held echocardiography appears to have important limitations
      in specific clinical settings, such as shock, pulmonary hypertension, assessment
      of valvulopathy or valvular prosthesis, dynamic left outflow tract obstruction,
      left ventricular restriction or construction. The miniaturized system with
      spectral Doppler capability has not yet been properly validated in these
      indications. At its present stage of development, hand-carried ultrasound units
      do not allow to perform a comprehensive examination which relies on the use of a
      full-feature system, especially when a precise hemodynamic evaluation is
      required. Diagnostic ability of hand-held echocardiography is similar to that of
      upper-end platforms for diagnoses based on two-dimensional imaging: left
      ventricular systolic function, detection of wall motion abnormalities, size of
      cardiac chambers, identification of pericardial or pleural effusions. Hand
      carried ultrasound devices may be considered as a "visual stethoscope" which
      provides an extension of the physical examination, but not as a potential
      alternative to standard transthoracic echocardiography. Its large potential
      clinical field of use raises the concern of taylored training programs to
      intensivists which could be focused on goal-directed echocardiographic
      examinations.

PMID- 15248448
TI  - Towards non-invasive, three-dimensional, high-resolution real-time imaging of the
      cardiovascular system.

PMID- 15248449
TI  - Magnetic resonance imaging of acute myocardial ischaemia and infarction.
AB  - Recent developments in cardiac magnetic resonance imaging (MRI) have led to
      tremendous breakthroughs in the imaging of acute myocardial ischaemia and
      infarction. Hardware and acquisition sequences have improved image quality while
      simplifying cardiac examinations. Cine-MRI allows for accurate time-resolved
      imaging of global and segmental left ventricular (LV) function with high spatial
      resolution. Dynamic multislice MRI of myocardial perfusion is now widely
      available allowing for the detection of microvascular obstruction after
      myocardial infarction (MI) or adding significant diagnostic value over usual
      clinical and biological markers after non ST elevation coronary syndromes. Direct
      high-resolution MRI of MI is well standardized with important clinical
      implications for the diagnosis of myocardial viability. In addition, stress
      cardiac MRI enables time-resolved analysis of myocardial perfusion under
      pharmacological stress, or accurate assessment of regional LV function during
      dobutamine cine-MRI for detection of myocardial ischaemia and/or viability. Non
      invasive MR coronary angiography is beyond the scope of this article.

PMID- 15248450
TI  - Molecular imaging for the diagnosis of high-risk plaque.
AB  - Despite advances in our understanding of the pathogenesis of atherosclerosis and
      new therapeutic modalities, the absence of an adequate method for early detection
      limits the prevention and treatment of the disease. High-resolution magnetic
      resonance has recently emerged as one of the most promising techniques for the
      non-invasive study of atherothrombotic disease, as it can characterize plaque
      composition and monitor progression. This review of plaque imaging focuses on the
      most recent technique: "molecular imaging", which uses specific contrast agents
      targeted to plaque components, and may allow for better stratification of "high
      risk" plaque and "high-risk" patients.

PMID- 15248451
TI  - Are adult cardiocytes still able to proliferate?
AB  - In all mammals including humans, adult cardiocytes become post mitotic cells,
      while cardiac non muscle cells still have the capacity to proliferate, and
      cardiac hypertrophy in adults is known to be due to cardiocyte hypertrophy and
      non muscle cell hyperplasia. Such a dogma was supported by several, rather
      ancient, observations, and has been recently challenged by two different groups.
      Several new paradigms in cell biology have modified these views: the entire
      determinants of the cell cycle are now entirely known; apoptosis, and cardiac
      apoptosis, is central in the process of cell division, and has a rather
      complicated significance; telomeres are specialized DNA-protein structures that
      prevent end-to-end chromosome fusion, and are rather characteristic of germ and
      stem cells, these structures are maintained by telomerase. Using several markers,
      including telomerase activity, endogenous self-renewing, clonogenic and
      multipotent stem cells were identified in the adult myocardium in human, mice and
      rat. These cells are activated during cardiac overload or ischemia to produce new
      cardiocytes. New endothelial cells also appeared, and are likely to have a
      circulatory origin. The physiological importance of these new cells is debatable
      at the moment. Nevertheless, these findings provide an important new basis for
      cell cardiomyoplasty. It is also possible to envisage stimulation of the
      production and activity of these new cells to compensate for the lack of
      substance after myocardial infarction.

PMID- 15248452
TI  - [Myocardial infarction revealing an antiphospholipid syndrome in a 27-year-old
      woman].
AB  - We report the case of a 27 year old woman, with no vascular risk factors other
      than moderate smoking, admitted for a first acute anterior myocardial infarction.
      Emergency coronarography detected an isolated thrombosis, localised at the level
      of the middle section of the anterior inter-ventricular artery in an otherwise
      normal coronary network. Angioplasty of the artery with direct stenting was
      performed successfully and the follow up was uncomplicated. The diagnosis of
      primary antiphospholipid syndrome was made on the association of a raised level
      of anti-cardiolipin antibodies and the absence of elements in favour of an
      associated connective tissue disorder.

PMID- 15248453
TI  - [Psychiatric complication of an implanted automatic defibrillator].
AB  - The implantable automatic defibrillator has completely changed the prognosis of
      potentially fatal ventricular arrhythmias by the delivery of an electric shock in
      the event of ventricular tachycardia or fibrillation. This vital device is
      sometimes poorly accepted from the psychological point of view by patients having
      been traumatised by experiences of sudden death from which they have been
      rescuscitated. Anxiety and depression are common and they have an important
      effect on the quality of life. The unpredictable occurrence of painful, multiple
      and uncontrollable electrical shocks may induce a state of acute stress with
      stunning, the resemblance of which to the model of learned helplessness described
      experimentally in the animal by Seligman, is discussed. The authors report the
      case of a 20 year old man whose automatic defibrillator was activated twenty
      times in one night. His state of stress and impotence was such that he lay
      prostate in his bed. Suicide seemed to be the only possible way of escaping from
      the electrical shocks of the device which was perceived as being dangerous. The
      management of this condition is not standardised but it requires the
      collaboration of the cardiac rhythmological and psychiatric teams. Medication
      with antidepressant drugs alone is not sufficient. The regulation of the
      sensitivity of the defibrillator gives the patient a feeling of mastering the
      situation: submission is not total! Research along this line should improve the
      patients' acceptation of the device and their quality of life.

PMID- 15248454
TI  - Radioactive microspheres in therapeutics.
AB  - Microspheres as a drug delivery system hold great promise in reaching the goal of
      controlled drug delivery as well as site specific delivery. In the last few
      decades, scientific and technological advancements have been made in the research
      and development of radiolabeled microspheres. These are used successfully for the
      treatment of various cancers and tumors. Since response to chemotherapy and
      external radiotherapy is not so effective and hazardous too, so an alternative to
      this is internal radiation therapy. These radiolabeled microspheres are very
      stable and have a proven efficacy in the field of primary as well as metastatic
      cancers. Radioactive microspheres can be selectively targeted to various tumors
      without undue radiation to the nontumorous tissues. The radioactive microspheres
      are injected to halt tumor growth via the blood supply, thereby enabling surgical
      removal once the tumor size decreases. This review provides an outlook to various
      aspects of radioactive microspheres and their role in treatment of various tumors
      and cancers.

PMID- 15248455
TI  - Novel enantiopure ferrugininoids active as nicotinic agents: synthesis and
      radioligand binding studies.
AB  - A series of hitherto unknown enantiopure (-)-ferruginine analogues of type 8 and
      9 was prepared and tested for the affinity toward the nicotinic acetylcholine
      receptor (nAChR) subtypes (alpha4)2(beta2)3, alpha7*, alpha3beta4*, and
      (alpha1)2beta1gamma delta. The stereoconservative asymmetric syntheses started
      with (-)-cocainhydrochloride (10) from the chiral pool which was transformed into
      the chiral building blocks (+)-2-tropanone (11) and to (-)-anhydroecgonine (18).
      Key steps of the syntheses are novel extensions to existing methodology e.g. a
      Suzuki Pd(0)-mediated cross-coupling of vinyl triflate (12) with the heteroaryl
      organoboranes 13-15 and an inverse type [4+2]-cycloaddition with 1,2,4,5
      tetrazine (21). The bioisosteric replacement of the 3-acetyl pharmacophoric
      element of the lead 6 by a 3-pyridyl, 5-chloropyridyl, 5-pyrimidinyl, 2
      pyrazinyl, or 4-pyridazinyl moiety resulted in nAChR ligands with Ki-values
      ranging from 1.1-713 nM toward the (alpha4)2(beta2)3 subtype combined with
      significant differentiation among the nAChR subtypes when tested in vitro by
      radioligand binding studies. Generally the ferrugininoids are less potent than
      the corresponding norferrugininoids. Similar to results of the norferrugininoid
      series the novel azine substituted ferrugininoids 8 proved to be more potent than
      the diazine analogues 9; both exhibited higher affinities compared to the lead 6.
      The 5-chloropyridyl-containing variant 8b [1R, 5S)-enantiomer] turned out to be
      the most active nAChR ligand with a 12-fold higher affinity toward the
      (alpha4)2(beta2)3 subtype than the corresponding (1S, 5R)-form ent-8b.

PMID- 15248456
TI  - Synthesis of chloro and bromo substituted 5-(indan-1'-yl)tetrazoles and 5-(indan
      1'-yl)methyltetrazoles as possible analgesic agents.
AB  - Chloro and bromo substututed indanyl tetrazoles (compounds 5a, b) and indanyl
      methyltetrazoles (compounds 5c, 5d) have been synthesized from their respective
      acids through amide and nitrile routes, and characterized. The title compounds
      (5a, 5b, 5c and 5d) were subjected for their analgesic activity in the acetic
      acid induced writhing test on albino mice. The significant (p < 0.001) analgesic
      activity, exhibited by the compound 5b at a dose of 50 mg/kg body weight, was
      comparable to that of phenylbutazone and indometacin at a dose of 100 and 50
      mg/kg body weight respectively. The effect of substitution at the benzenoid part
      of the indan nucleus and chain lenght on analgesic activity was in the following
      order: bromine > chlorine and tetrazole > methyltetrazole.

PMID- 15248457
TI  - [Thieno[2,3-c]quinolines - synthesis and biological investigation].
AB  - pH-Dependant reduction of the methyl 3-(2-nitrophenyl)thiophene-2-carboxylate
      (3), obtained by Suzuki cross-coupling of the methyl 3-iodothiophene-2
      carboxylate with 2-nitrophenyl boronic acid yields the cyclic hydroxamic acid 4
      and the lactam 5, respectively. The lactam 5 is also formed by reacting the
      compound 2 with pinacolato 2-aminophenylboronate. The 4-chlorothieno[2,3
      c]quinoline 6 is formed from the lactam 5 by heating with POCl3/PCl5. Melting of
      6 with the novaldiamine base in phenol gives the chloroquine analogue 7, whereas
      the amodiaquine and the cycloquine analogues 8 and 9 are obtained using phenol
      Mannich bases. The hydroxamic acid 4 has a moderate effect on eicosanoid
      biosynthesis in human whole blood. The growth of the chloroquine resistent
      Plasmodium falciparum strain Dd2 is inhibited by the pyronaridine derivative 9
      with an IC50 value of 650 nM.

PMID- 15248458
TI  - [[1]Benzofuro[3,2-b]pyridin-4-yl-amines - synthesis and investigation of activity
      against malaria].
AB  - The ethyl 4-chlorobenzofuro[3,2-b]pyridine-3-carboxylate (2) reacted with the
      hydrochlorides of the mono- and bis-phenol Mannich bases 3 to yield the
      amodiaquine and pyronaridine analogues 4. The chloroquine analogue 6 was formed
      by melting 2 with the novaldiamine base (5) in phenol. The most active compound
      4c inhibited the growth of the malaria parasite Plasmodium falciparum with an
      IC50 of 500 nM.

PMID- 15248459
TI  - Stability control of valerian ground material and extracts: a new HPLC-method for
      the routine quantification of valerenic acids and lignans.
AB  - A new HPLC-method for the separation of medium polar and nonpolar compounds in
      preparations of Valeriana officinalis was established for stability control.
      Powdered valerian root and a commercial ethanolic valerian extract were
      investigated for apparent differences in stability behaviour. Storage conditions
      were chosen according to the ICH-guidelines. Changes in composition of valerenic
      acids and lignans were observed depending on storage conditions and packaging
      materials. Hydroxyvalerenic acid, pinoresinol and hydroxypinoresinol were
      identified as degradation products in Valerian root, especially during
      accelerated testing. Ethanolic extracts appeared not to be as sensitive for
      chemical degradation under climatic influences compared to the crude plant
      material, and showed no increase in the amounts of lignan-aglyka. In comparison,
      extracts showed high sensitivity on changes of physical properties like loss on
      drying and viscosity.

PMID- 15248460
TI  - Comparison of derivative spectrophotometric and liquid chromatographic methods
      for the determination of rofecoxib.
AB  - Two different UV spectrophotometric methods were developed for the determination
      of rofecoxib in bulk form and in pharmaceutical formulations. The first method,
      an UV spectrophotometric procedure, was based on the linear relationship between
      the rofecoxib concentration and the lambdamax amplitude at 279 nm. The second
      one, the first derivative spectrophotometry, was based on the linear relationship
      between the rofecoxib concentration and the first derivative amplitude at 228,
      256 and 308 nm. Calibration curves were linear in the concentration range using
      peak to zero 1.5-35.0 microg x ml(-1). HPLC was carried out at 225 nm with a
      partisil 5 ODS (3) column and a mobile phase constituted of acetonitrile and
      water (50 :50 v/v). A linear range was found to be 0.05-35.0 microg x ml(-1). The
      developed methods were successfully applied for the assay of pharmaceutical
      dosage form. The statistics of the analytical data is also presented. The results
      obtained by first derivative spectrophotometry were compared with HPLC and no
      significant difference was found.

PMID- 15248461
TI  - Photostability of epinephrine - the influence of bisulfite and degradation
      products.
AB  - Sulfites are previously demonstrated to increase the photodegradation of
      epinephrine. The aim of this study was to clarify the factors responsible for
      this effect. Adrenochrome sulfonate seems to be the important substance.
      Photoproduction of singlet oxygen is indicated to be the mechanism by which
      adrenochrome sulfonate acts. Protection of epinephrine solutions from irradiation
      <418 nm prevented the photodegradation. A reaction pathway for thephotochemical
      decomposition of epinephrine in the presence of bisulfite is suggested.

PMID- 15248462
TI  - Cultivation and characterization of a bovine in vitro model of the cornea.
AB  - The aim of this study was to develop an in vitro model of the cornea of bovine
      cells, to characterise the model by histochemical methods and to investigate
      permeation of ophthalmic drugs through the model. As in the in vivo situation, an
      in vitro model of the cornea should consist of all three different types of
      cells. In the current study, the construction of the in vitro cornea was
      performed using cells prepared from primary cultures. To investigate the state of
      the cells in the cultures, growth curves were established. Immunocytochemical
      determination of keratin and vimentin was performed for all three isolated and
      sub-cultivated cell types of the bovine cornea. To further simulate the in vivo
      conditions, corneal epithelial cells were seeded onto the collagen-gel base
      containing the stromal cells with an underlying sheet of endothelium. Permeation
      experiments were performed with pilocarpine hydrochloride and timolol hydrogen
      maleate as model drugs and excised bovine cornea and the in vitro cornea as
      permeation barriers. The immunohistochemical investigations show that excised
      bovine cornea and the in vitro model of the cornea are comparable with respect to
      the expression of keratin K3, indicating that the primarily isolated cells
      correspond to the different cell types of the cornea. Culturing of the epithelial
      cells on the complex basis has led to the formation of a corneal epithelium with
      several layers, closely resembling the morphology of the in vivo epithelium.
      Although the permeation rates of the drug through the in vitro cornea were always
      higher, the sequence in which the drugs permeate through the two types of
      barriers was the same. The drug permeation through the in vitro cornea may
      therefore be a useful predictive tool to estimate the permeability coefficients
      of drugs through excised cornea.

PMID- 15248463
TI  - [Liberation of hydrocortisone acetate from different commercial formulations].
AB  - Liberation of hydrocortisone acetate from different commercial formulations In
      this article the release of hydrocortisone acetate (HC-acetate) from three
      commercial semisolid formulations (Ebeno-ointment, Soventol HC cream and Fenistil
      hydrocortisone ointment) was measured by means of a multilayer membrane system
      (MLMS) described in the literature. The formulations are different regarding rate
      and extent of the release of HC-acetate. The release of HC-acetate form the
      Soventol HC cream is very fast and results in high topical availability. In
      contrast, HC-acetate shows a sustained release from the Fenistil hydrocortisone
      ointment. The release of HC-acetate from the Ebenol-ointment is between that of
      the Soventol HC cream and that of the Fenistil-ointment. In summary, HC-acetate
      shows a shorter mean liberation time (MDT) and a higher topical availability from
      Soventol HC cream in comparison to the other formulations studied.

PMID- 15248464
TI  - Effect of exogenous leptin administration on high fat diet induced oxidative
      stress.
AB  - The objective of the present study was to explore the tissue lipid peroxidation
      and antioxidant status in mice receiving exogenous leptin along with high fat
      diet for a period of 6 weeks. Significantly elevated levels of tissue
      thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and
      significantly lowered levels of glutathione and its related enzymes were observed
      in the liver, heart and kidney of mice fed with a high fat diet as compared with
      the control mice fed with a standard pellet diet. Subsequent to the treatment
      with high fat diet (ie., after the initial period of 30 days) exogenous leptin
      (230 microg kg(-1) body weight) was simultaneously administered along with the
      regular high fat diet every alternate day for 15 days. Leptin administration
      significantly lowered the tissue levels of TBARS, CD and elevated the activities
      of reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S
      transferase (GST) in both the control and high fat diet fed mice. Thus leptin
      supplementation was found to be effective in attenuating high fat diet induced
      oxidative stress.

PMID- 15248465
TI  - Bioconversion studies in cultured cells of Corydalis species.
AB  - Structural analysis of the metabolites of dopamine and salsolinol in cultured
      cells of Corydalis species was carried out using the combination of LC-MS and LC
      NMR techniques. Metabolic pathways were clarified without the need to isolate the
      individual metabolites.

PMID- 15248466
TI  - Flavonoid and methoxyellagic acid sodium sulphates from Frankenia laevis L.
AB  - Two new flavonol di-sodium sulphates and an ellagic acid methyl ether mono-sodium
      sulphate have been found in the aqueous alcohol whole plant extract of Frankenia
      laevis L. They have been identified as the 3,7-di-sodium sulphate of kaempferol,
      the 3,7-di-sodium sulphates of quercetin and the 4'-mono-sodium sulphate of
      ellagic acid-3-methyl ether. Also, five known compounds have been isolated and
      characterized from the same extract. Establishment of all structures has been
      achieved mainly, by ESI-MS and NMR.

PMID- 15248467
TI  - Constituents of Carapa guianensis Aubl. (Meliaceae).
AB  - Nine compounds were isolated from the EtOH extraction of the twig of Carapa
      guianensis Aubl. On the basis of spectroscopic methods, their structures were
      elucidated as 1,3-di-benzene carbon amine-2-octadecylic acid-glyceride (1),
      hexacosanoic acid-2,3-dihydroxy-glyceride (2), ursolic acid (3), naringenin (4),
      scopoletin (5), 3,4-dihydroxymethylbenzoate (6), 2,6-dihydroxymethylbenzoate (7),
      tetratriacontanoic acid (8), triacontanoic acid (9) respectively. Among them 1
      was new, 2 was firstly isolated from nature, and 3-9 were obtained from this
      plant for the first time.

PMID- 15248468
TI  - Dehydroepiandrosterone sulfate increases hepatic ubiquinone-9 in male F-344 rats.
AB  - Administration of dehydroepiandrosterone sulfate (DHEAS) for 14 days caused a
      significant increase in the total ubiquinone-9 level in the hepatic tissue of
      male F-344 rats (p < 0.05). Hepatic ubiquinone-10 level of DHEAS-treated rats
      however, was found not to be statistically different from control animals. These
      findings suggest that peroxisome proliferator DHEAS displays typical hepatic
      response in increasing ubiquinone concentration in the rat.

PMID- 15248469
TI  - Trypanocidal activity of bergenin, the major constituent of Flueggea virosa, on
      Trypanosoma brucei.
AB  - The presence of bergenin in substantial amounts in the methanol leaves extract of
      Flueggea virosa (Euphorbiaceae) was established as a strong chemotaxomic point of
      differentiation between Flueggea virosa and Securinega virosa. Bergenin showed an
      inhibitory effect on the growth of the bloodstream form of Trypanosoma brucei
      with an IC50 value of 1 microM.

PMID- 15248470
TI  - Receipt of assistance and extended family residence among elderly men in Mexico.
AB  - This article focuses on help received by a nationally-representative sample of
      2,376 Mexican men age 60+ in 1994. In the month before the interview, about one
      half of the men received in-kind or domestic assistance, two-fifths received
      financial assistance, and about one-fourth received physical assistance. This was
      so even as almost half the men still worked, and over half (57%) had no
      discernable functional limitation. Using logistic regression, the study found
      support for the common assumption that living arrangements are an important
      predictor of assistance. Other factors are important too however. In fact, many
      elders received help from non-coresiding relatives. Beside financial remittances,
      help from non-coresiding relatives included in-kind, domestic, and physical
      assistance. Research on Mexico suggests that we need to revisit notions of a
      modified extended family in which non-coresidential ties can be important.
      Surveys need questions about frequency of contact and geographic distance between
      elderly people and their kin.

PMID- 15248471
TI  - Predictors and characteristics of Erikson's life cycle model among men: a 32-year
      longitudinal study.
AB  - To assess Erikson's life cycle model, 86 men, initially selected for health, were
      prospectively studied at age 21, and reassessed 32 years later at age 53. Using
      the Vaillant and Milofsky (1980) modification of Erikson's model, 48 men (56%)
      achieved generativity, an advanced developmental stage, at follow-up. Results
      generally support Erikson's model and show that generativity was significantly
      associated with successful marriage, work achievements, close friendships,
      altruistic behaviors, and overall mental health. Successful young adult
      predictors of Erikson's model at midlife included a warm family environment, an
      absence of troubled parental discipline, a mentor relationship, and, most
      importantly, favorable peer group relationships. Significant predictors of
      Erikson's model were of moderate effect size and involve young adult social
      relationships rather than physical symptoms or parental social class standing.

PMID- 15248472
TI  - Deconstructing positive affect in later life: a differential functionalist
      analysis of joy and interest.
AB  - Positive affect, an index of psychological well-being, is a known predictor of
      functionality and health in later life. Measures typically studied include joy,
      happiness, and subjective well-being, but less often interest--a positive emotion
      with functional properties that differ from joy or happiness. Following
      differential emotions theory, the present study measured trait joy and interest
      in a population-based sample of 1,118 adults aged 65-86 years. As predicted,
      trait joy was associated with greater religious participation, while trait
      interest was associated with greater education. Joy was associated with lower
      morbidity and stress while interest was not. Interest was, in fact, associated
      with greater stress. Both emotions were positively associated with social
      support. We use the pattern of predictors to develop a functionalist
      conceptualization of these two emotions in later life, concluding that it is
      worthwhile to treat interest and joy as partially-independent positive affects
      contributing differentially to human emotionality and later life adaptation.

PMID- 15248473
TI  - Autobiographical memory from a life span perspective.
AB  - This comparative study (i.e., three age groups, three measures) explores the
      distribution of retrospective and prospective autobiographical memory data across
      the lifespan, in particular the bump pattern of disproportionally higher recall
      of memories from the ages 10 to 30, as generally observed in older age groups, in
      conjunction with the well-known recency effect. The memory data patterns of the
      Life-line Interview Method (LIM, the measure of this study, were compared to the
      published data patterns of two other memory measures (i.e., the Time Line and
      Life event sorting task). The results of this comparative study confirm the
      universality of the bump for older adults, as well as the recency effect. From
      the LIM data patterns it is hypothesized that both bump and recency effects play
      a part not only in middle-aged and older adults but also in younger people. In
      search for an explanation of these patterns, a theoretical outline is presented
      for the study of autobiographical memory as a dynamic system of both
      retrospective and prospective memory, subject to continuous changes across the
      lifespan.

PMID- 15248474
TI  - Genetic alterations in cervical cancer.
AB  - In the pathogenesis of cervical cancer the role of human papillomavirus (HPV)
      infection is well established. However, other than HPV infection the genetics of
      cervical cancer remains poorly understood. In the pathogenesis of cervical cancel
      three major factors are involved, two of which are related to the presence of HPV
      and the third is the recurrent genetic alterations not linked to HPV infection.
      Several chromosomal regions with recurrent loss of heterozygosity (LOH) in
      cervical cancer have been identified. However; the putative tumor suppressor
      genes located in these chromosomal locations are yet to be identified. Recurrent
      amplifications have been mapped to the short arm of chromosome 3 in invasive
      cancer. Microsatellite instability and mutator phenotype do not play a major role
      in cervical carcinogenesis. As in other cancers, cervical cancer too requires the
      accumulation of genetic alterations for carcinogenesis to occur. Identification
      of these alterations could help to provide a better understanding of the disease
      and thus improve treatment.

PMID- 15248475
TI  - Circadian clock genes in Drosophila: recent developments.
AB  - Circadian rhythms provide a temporal framework to living organisms and are
      established in a majority of eukaryotes and in a few prokaryotes. The molecular
      mechanisms of circadian clock is constantly being investigated in Drosophila
      melanogaster. The core of the clock mechanism was described by a transcription
      translation feedback loop model involving period (per), timeless (tim), dclock
      and cycle genes. However, recent research has identified multiple feedback loops
      controlling rhythm generation and expression. Novel mutations of timeless throw
      more light on the functions of per and tim products. Analysis of pdf neuropeptide
      gene (expressed in circadian pacemaker cells in Drosophila), indicate that PDF
      acts as the principal circadian transmitter and is involved in output pathways.
      The product of cryptochrome is known to function as a circadian photoreceptor as
      well as component of the circadian clock. This review focuses on the recent
      progress in the field of molecular rhythm research in the fruit fly. The gene(s)
      and the gene product(s) that are involved in the transmission of environmental
      information to the clock, as well as the timing signals from the clock outward to
      cellular functions are remain to be determined.

PMID- 15248476
TI  - Brain tumor inhibition in experimental model by restorative immunotherapy with a
      corpuscular antigen.
AB  - In view of the advances in our understanding of anti-tumor immune response, it is
      now tempting to contemplate the development of immunotherapies for malignant
      brain tumors, for which no effective treatment exists. Immunotherapy, with agents
      known as biological response modifiers (BRMs) are thus gaining increasing
      interest as the fourth modality of treatment. A non-specific BRM, sheep
      erythrocytes (SRBC) when administered (ip, 7% PCV/V, 0.5 ml) in a group of
      animals at the end of seventh month of ethylnitrosourea administration, resulted
      in significant increase in the mean survival time (> 350 days). Studies conducted
      for growth kinetics pattern with proliferation index and fluorochrome (HO-33342)
      uptake techniques at the tissue culture level exhibited a regulatory inhibition
      of the cells isolated from tissue excised from the tumor susceptible area of
      brain of SRBC treated animals. Moreover, histological examination of brain from
      animals showed immunomodulatory role of SRBC in experimentally induced brain
      tumor. Further probe into the mechanisms involving immunological investigations
      at the cellular level in these animals indicated an augmented and potentiated
      cell mediated immune response (CMI) as evidenced by enhanced spontaneous rosette
      forming capacity and cytotoxic activity of lymphocytes and neutrophil (PMN)
      mediated phagocytosis respectively. The observations suggest that SRBC down
      regulate malignant growth pattern of experimental brain tumors either by an
      immunologically enhanced killing of tumor cells and/or by directly inhibiting the
      tumor growth possibly via a stimulated cytokine network. Thus, a corpuscular
      antigen, can potentiate CMI response in experimentally induced brain tumor animal
      model, in which response induced in the periphery are able to mediate anti-tumor
      effects in the brain.

PMID- 15248477
TI  - Inhibition of membrane Na(+)-K+ Atpase of the brain, liver and RBC in rats
      administered di(2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl
      chloride (PVC) blood storage bags.
AB  - Significant amounts of di(2-ethylhexyl) phthalate (DEHP) leach out into blood
      stored in DEHP plasticized polyvinyl chloride (PVC) bags resulting in the
      exposure of recipients of blood transfusion to this compound. The aim of this
      study was to find out whether DEHP at these low levels has any effect on the
      activity of membrane Na(+)-K+ ATPase, since a decrease in this enzyme activity
      has been reported to take place in a number of disorders like neurodegenerative
      and psychiatric disorders, coronary artery disease and stroke, syndrome-X,
      tumours etc. DEHP was administered (ip) at a low dose of 750 microg/100 g body
      weight to rats and the activity of membrane Na(+)-K+ ATPase in liver, brain and
      RBC was estimated. Histopathology of brain, activity of HMG CoA reductase (a
      major rate limiting enzyme in the isoprenoid pathway of which digoxin, the
      physiological inhibitor of Na(+)-K+ ATPase is a product), intracellular
      concentration of Ca2+ and Mg2+ in RBC (which is altered as a result of inhibition
      of Na(+)-K+ ATPase) were also studied. (In the light of the observation of
      increase of intracellular Ca2+ load and intracellular depletion of Mg2+ when
      Na(+)-K+ ATPase is inhibited). Histopathology of brain revealed areas of
      degeneration in the rats administered DEHP. There was significant inhibition of
      membrane Na(+)-K+ ATPase in brain, liver and RBC. Intracellular Ca2+ increased in
      the RBC while intracellular Mg2+ decreased. However activity of hepatic HMG CoA
      reductase decreased. Activity of Na(+)-K+ ATPase and HMG CoA reductase, however
      returned to normal levels within 7 days of stopping administration of DEHP. The
      inhibition of membrane Na(+)-K+ ATPase activity by DEHP may indicate the
      possibility of predisposing recipients of transfusion of blood or hemodialysis to
      the various disorders mentioned above. However since this effect is reversed when
      DEHP administration is stopped, it may not be a serious problem in the case of a
      few transfusion; but in patients receiving repeated blood transfusion as in
      thalassemia patients or patients undergoing hemodialysis, possibility of this
      risk has to be considered. This inhibition is a direct effect of DEHP or its
      metabolites, since activity of HMG CoA reductase, (an enzyme which catalyses a
      major rate limiting step in the isoprenoid pathway by which digoxin, the
      physiological inhibitor of Na(+)-K+ ATPase is synthesized) showed a decrease.

PMID- 15248478
TI  - Isolation of etiological agent of hydropericardium syndrome in chicken embryo
      liver cell culture and its serological characterization.
AB  - The virus causing hydropericardium syndrome was isolated in chicken embryo liver
      (CEL) cell culture from livers obtained from naturally infected broilers. The
      cytopathic effects characterized by rounding and degeneration of cells were
      visible 36 hr post infection in first passage. At 4th passage level, the
      infectivity titre was 5.24 log10 TCID50/ml. In May-Grunwald and Giemsa stained
      cells, basophilic intranuclear inclusions ('bird eye' inclusion), typical of
      aviadenovirus infection, were observed. The specificity of inclusion was
      confirmed by indirect immunofluorescence. Various serological tests, such as agar
      gel precipitation test, counter immuno electrophoresis, micro serum
      neutralization test and enzyme linked immunosorbent assay were also standardized
      to confirm the isolation of etiological agent of hydropericardium syndrome in CEL
      cell culture and to diagnose the disease in poultry.

PMID- 15248479
TI  - Lupeol, a triterpene, prevents free radical mediated macromolecular damage and
      alleviates benzoyl peroxide induced biochemical alterations in murine skin.
AB  - In our earlier communication we have shown that Lupeol inhibits early responses
      of tumour induction in murine skin. The free radical mediated damage to the
      cellular macromolecules such as DNA, proteins, lipids and alteration in the
      activities of quinone reductase and xanthine oxidase are important biochemical
      parameters of tumor development. The suppression of free radical mediated damage
      to cellular macromolecules and induction of quinone reductase along with
      depletion of xanthine oxidase are prominent characteristics of chemopreventive
      agents. In the present investigation, we have elucidated the mechanism of action
      of lupeol (Lup-20 (29)-en-3beta-ol), a triterpene found in moderate amount in
      many vegetables, fruits and anti-tumor herbs. In the present investigation,
      lupeol significantly reduced the free radical mediated DNA-sugar damage and
      microsomal lipid peroxidation in an iron/ascorbate free radical generating system
      in vitro. Benzoyl peroxide, a known free radical generating tumor promoter
      mediated oxidation of proteins and modulation in the activities of quinone
      reductase as well as xanthine oxidase was significantly prevented by lupeol when
      tested on murine skin in vivo. It was concluded from this study that lupeol acts
      as an effective chemopreventive agent against cutaneous toxicity.

PMID- 15248480
TI  - Chronic low dose exposure to hydrogen peroxide changes sensitivity of V79 cells
      to different damaging agents.
AB  - Chinese hamster V79 cells were repeatedly exposed to a low dose of hydrogen
      peroxide (H2O2) over several weeks and then exposed to H2O2, cisplatin or
      ultraviolet (UV) light. Cell killing was examined by colony formation, following
      these treatments. It was seen that cells conditioned by multiple low doses of
      H2O2 showed resistance to killing in case of H2O2 and cisplatin but the
      sensitivity to UV light was same as the control cells. Apoptosis was also
      determined in these cells after the same treatments. UV light failed to induce
      apoptosis in both conditioned and in control cells, but in case of cells treated
      with H2O2 and with cisplatin, there was less apoptosis in the conditioned cells
      compared to the control cells. From our observation we can say that the enhanced
      survival of cells after treatment with H2O2 or cisplatin could be due to
      inhibition of apoptosis.

PMID- 15248481
TI  - Bacterial dynamics associated with algal antibacterial substances during post
      harvest desiccation process of Sargassum stolonifolium Phang et Yoshida.
AB  - Brown algae of genus Sargassum are known to produce relatively higher amount of
      alginic acid. Optimal extraction of this algalcolloid for local consumption
      requires in-depth studies on post-harvest treatment of the algal fronds. Present
      investigation endeavors to establish the dynamics and inter-relationship of
      moisture content and bacteria found on the surface of the alga and alginic acid
      content during post-harvest desiccation of Sargassum stolonifolium Phang et
      Yoshida. Harvested fronds were subjected to desiccation for 31 days and bacterial
      dynamics were monitored with relation to moisture content and water activity
      index (a(w)). There was 85% decrease in moisture content, however, a(w) showed a
      more gradual decrease. Total bacterial count increased during the first week and
      attained maximal value on day 7. Thereafter, a drastic decrease was seen until
      day 14, followed by a gradual decline. Six species of bacteria were isolated and
      identified, i.e. Azomonas punctata, Azomonas sp., Escherichia coli, Micrococcus
      sp., Proteus vulgaris and Vibrio alginolyticus. Calculated ratios for increase in
      alginic acid content and decrease in moisture content were almost the same
      throughout the desiccation process, implying that extracellular alginase
      producing bacteria did not use the alginic acid produced by the algae as its
      carbon source. It became apparent that drastic decrease in bacterial count after
      day 7 could not be attributed to salinity, moisture content, a(w) or lack of
      carbon source for the bacteria. The possible exposure of these bacteria to algal
      cell sap which is formed due to the rupture of algal cells was seen as the most
      likely reason for the drop in bacterial population. Scanning electron microscope
      (SEM) micrograph taken on day 10 of desiccation showed the presence of cracks and
      localities where bacteria were exposed to algal cell sap. In vitro antibacterial
      tests were carried out to verify the effect of algal extracts. Separation and
      purification of crude algal extracts via bioassay guided separation methodology
      revealed the identity of active compounds (i.e. gylcolipids and free fatty acids)
      involved in this inherently available antibacterial defense mechanism during
      algal desiccation.

PMID- 15248482
TI  - Effects of hypothyroidism induced by 6-n-propylthiouracil and its reversal by T3
      on rat heart superoxide dismutase, catalase and lipid peroxidation.
AB  - The present study critically evaluates the effects of hypothyroid and
      hyperthyroid states on lipid peroxidation and two enzymes of active oxygen
      metabolism, namely superoxide dismutase (SOD) and catalase (CAT) in the rat heart
      mitochondrial and post-mitochondrial fractions. Lipid peroxidation, an index of
      oxidative stress, was elevated in the heart tissue in hypothyroid state but
      reduced upon T3 supplementation. Hyperthyroidism registered increased SOD
      activity in post-mitochondrial fraction. Mitochondrial SOD activity was reduced
      in hypothyroid state, which was further reduced by T3 administration. In
      contrast, different thyroid states had no effect on catalase activity in the
      mitochondrial fraction. The hypothyroid state however, significantly augmented
      catalase activity in post-mitochondrial fraction. The results suggest that the
      antioxidant defence status of cardiac tissue is well modulated by thyroid
      hormone.

PMID- 15248483
TI  - Regional variations in fibre growth dynamics of myotomal and caudal fin muscles
      in relation to body size of a freshwater teleost, Barbus sarana (Cuv. & Val.).
AB  - The growth of red fibres in anterior and middle myotomal regions of B. sarana was
      mainly by hyperplasia in smaller size classes. In higher size classes, growth by
      hyperplasia was greater in posterior myotomal region compared to the other two
      myotomal regions. The growth of pink fibres in anterior myotomal regions was
      mainly by hypertrophy. The middle and posterior myotomal regions showed fibre
      growth by hyperplasia. The growth dynamics of white fibres revealed more or less
      similar pattern in all three myotomal regions against the somatic development.
      White fibres grew by hyperplasia up to 8 cm F.L. size classes and thereafter by
      hypertrophy. However, in > 12 cm F.L. size classes, the mean diameter of white
      fibres did not increase significantly. Similar pattern of growth was found in the
      white fibres of caudal fin muscle. It is interesting to note that the hyperplasia
      was mostly completed in the white fibres of the smallest fish studies, whereas,
      it continued to quite larger fish size in red and pink fibres. Thus, hyperplasia
      and hypertrophy may be responsible for growth in all fibre types in all myotomal
      regions in relation to somatic development in this small and medium growing
      species.

PMID- 15248484
TI  - Lipid peroxidation and antioxidant systems in the blood of young rats subjected
      to chronic fluoride toxicity.
AB  - Wistar albino rats were exposed to 30 or 100 ppm fluoride in drinking water
      during their fetal, weanling and post-weaning stages of life up to puberty.
      Extent of lipid peroxidation and response of the antioxidant systems in red blood
      cells and plasma to prolonged fluoride exposure were assessed in these rats in
      comparison to the control rats fed with permissible level (0.5 ppm) of fluoride.
      Rats treated with 100 ppm fluoride showed enhanced lipid peroxidation as
      evidenced by elevated malondialdehyde (MDA) levels in red blood cells but, 30 ppm
      fluoride did not cause any appreciable change in RBC MDA level. 30 ppm fluoride
      intake resulted in increased levels of total and reduced glutathione in red blood
      cells and ascorbic acid in plasma while 100 ppm fluoride resulted in decreases in
      these levels. The activity of RBC glutathione peroxidase was elevated in both the
      fluoride-treated groups, more pronounced increase was seen with 100 ppm. Reduced
      to total glutathione ratio in RBC and uric acid levels in plasma decreased in
      both the groups. RBC superoxide dismutase activity decreased significantly on
      high-fluoride treatment. These results suggest that long-term high-fluoride
      intake at the early developing stages of life enhances oxidative stress in the
      blood, thereby disturbing the antioxidant defense of rats. Increased oxidative
      stress could be one of the mediating factors in the pathogenesis of toxic
      manifestations of fluoride.

PMID- 15248485
TI  - Efficacies of plant phenolic compounds on sodium butyrate induced anti-tumour
      activity.
AB  - The ability of the differentiation inducing agent sodium butyrate (NaB) alone or
      combined with plant-derived phenolic compounds to produce growth inhibition in
      human erythroleukemic cells was investigated. As a single agent, curcumin
      produced a marked inhibition of proliferation indicated by its low concentration
      used. The effect of phenolics on the cell cycle could probably contribute to the
      augmented antiproliferative activity of NaB. The present data show that quercetin
      produced synergistic effect in terms of cell killing in association with NaB.
      Both curcumin and ferulic acid potentiated NaB-induced reduction of cell number.
      When NaB was added before exposure to graded doses of quercetin it did induce a
      greater inhibitory effect. The combination of NaB and quercetin seems less
      effective on S180 ascites tumour cells. As a single agent quercetin was found to
      be the most efficacious on S180 tumour model.

PMID- 15248486
TI  - Phylogenetic analysis of symbiotic and free-living cyanobacterial cultures using
      DNA amplification fingerprinting.
AB  - DNA amplification fingerprinting (DAF) of 17 cyanobacterial isolates belonging to
      symbiotic and free-living forms of 6 different genera was done. The dendrogram
      analysis of 17 cyanobacterial cultures revealed three major clusters. All
      Westiellopsis cultures formed the first major cluster and their nucleotide
      relatedness ranged between 71-93%. In the second major cluster, the symbiotic
      cyanobacterium Anabaena sp dominated and all Anabaena cultures showed 60-75%
      similarity with each other. Nostoc muscorum is related to Anabaena variabilis by
      85% and formed the third major cluster. The dendrogram analysis of cyanobacterial
      isolates clearly revealed that free-living cyanobacterial cultures were closely
      related with each other and were diverse from the symbiotic forms.

PMID- 15248487
TI  - Influence of nutritional supplements on keratinolysis by Amycolatopsis
      keratinophila.
AB  - Keratinolytic potential of A. keratinophila (DSM 44409T), a newly described
      Amycolatopsis sp. isolated from cultivated soil in Kuwait, was demonstrated using
      keratinazure as the sole source of carbon and nitrogen as estimated by gel
      diffusion assay. Effects of 12 various nutritional supplements on the
      keratinolytic and azocollytic activities were determined. NH4H2PO4 and KNO3 in
      the medium supported a significantly higher keratinolytic activity than other
      supplements. However, azocollytic activities in all the supplemented media and
      the control were same. Best combination of carbon and nitrogen supplements
      (galactose and NH4H2PO4 respectively) used to evaluate the dynamics of growth and
      enzymes (keratinase and protease) activities of the isolate revealed a luxuriant
      growth with optimal keratinolytic activity occurring during the log phase. Other
      parameters of the fermentation medium, including pH, biomass accumulation, total
      protein and free amino acid concentrations were also studied.

PMID- 15248488
TI  - Free radical scavenging potential of Picrorhiza kurrooa Royle ex Benth.
AB  - For assessing free radical scavenging potential of P. kurrooa, the antioxidant
      activity of P. kurrooa extract was studied by lipid peroxidation assay using rat
      liver homogenate. The extract (1 mg/ml) showed marked protection (up to 66.68%)
      against peroxidation of liver phospholipids. Besides, reduced glutathione showed
      very encouraging activity. The extract also exhibited significant scavenging
      activity. Thus augmenting the wide use of plant in the indigenous system of
      medicine, which may partly be due to antioxidant and free radical scavening
      activity of the extract.

PMID- 15248489
TI  - Interrenal responses to high ambient temperature in soft-shelled turtle, Lissemys
      punctata punctata.
AB  - An exposure to ambient temperature of 25 degrees C had no perceptible effect on
      interrenal function but further increase of temperature to 35 degrees C caused
      nuclear hypertrophy with increase of nuclear diameter, RNA concentration, acid
      phosphatase and alkaline phosphatase activities, accompanied by quantitative
      depletions of cholesterol (free, esterified and total) and ascorbic acid levels
      in the interrenal gland of the soft-shelled turtle Lissemys p. punctata. Similar
      manifestations of stimulation, except in the nucleus, were marked after exposure
      to 38 degrees C, but the degree of response in respect of esterified and free
      cholesterol levels was higher at 38 degrees C than at 35 degrees C. Moreover,
      withdrawal of 38 degrees C temperature and subsequently maintaining at 25 degrees
      C for 15 days showed reverse manifestations to those of 35 degrees C/38 degrees
      C, leading to a tendency towards normalcy. It is suggested that high a ambient
      temperature of 35 degrees C significantly stimulates interrenal function of
      Lissemys turtles, but further increase of 38 degrees C does not cause further
      overall stimulation, and withdrawal of higher temperature (38 degrees C) shows a
      tendency towards normalcy. It is also suggested that (a) high ambient temperature
      causes thermal stress, (b) it is reversible and (c) it acts on interrenal
      activity presumably via CRF-ACTH-axis in turtles.

PMID- 15248490
TI  - Antifertility effect of Tinospora cordifolia (Willd.) stem extract in male rats.
AB  - Oral administration of 70% methanolic extract of T. cordifolia stem to male rats
      at the dose level of 100 mg/rat/day for 60 days did not cause body weight loss
      but decreased the weight of testes, epididymis, seminal vesicle and ventral
      prostate in a significant manner. Sperm motility as well as sperm density were
      reduced significantly which resulted in reduction of male fertility by 100%. The
      stem extract brought about an interference with spermatogenesis. The round
      spermatids were decreased by 73.12%. However, the population of preleptotene and
      pachytene spermatocytes were decreased by 47.60% and 52.85% respectively,
      followed by secondary spermatocytes (48.10%). Leydig cell nuclear area and mature
      Leydig cell numbers were significantly reduced when compared with controls. Serum
      testosterone levels showed significant reduction after Tinospora extract feeding.
      Seminiferous tubule diameter, Leydig cell nuclear area as well as cross sectional
      surface area of Sertoli cells were reduced significantly when compared to
      controls. Biochemical parameters i.e. protein, sialic acid, glycogen contents of
      testes decreased significantly. Seminal vesicular fructose also depleted whereas,
      testicular cholesterol was elevated significantly followed by a reduction in
      testosterone levels. These results suggested antifertility effects of the stem
      extract of T. cordifolia in male rats.

PMID- 15248491
TI  - Phytochemical investigation and evaluation of anti-inflammatory and anti
      arthritic activities of essential oil of Strobilanthus ixiocephala Benth.
AB  - Column chromatographic fractionation of essential oil obtained by
      hydrodistillation from the flowering tops of S. ixiocephala resulted in the
      isolation of beta-caryophyllene, fenchyl acetate, T-cadinol and a new
      sesquiterpene alcohol for which a name ixiocephol has been proposed. The beta
      caryophyllene and fenchyl acetate were identified by Co-TLC with authentic
      samples whereas T-cadinol and ixiocephol were structurally elucidated by UV, IR,
      1H NMR, 13C NMR and Mass spectral data. The GC-MS analysis of the essential oil
      has also revealed the presence of various monoterpenoids and sesquiterpenoids.
      The essential oil of S. ixiocephala demonstrated a dose dependant anti
      inflammatory activity in carrageenan-induced rat paw oedema. It has also revealed
      good activity in cotton pellet granuloma and adjuvant induced arthritis model in
      rats.

PMID- 15248493
TI  - Biosorption of Baftkar textile effluent.
AB  - Decolourization of wastewater from a textile plant by a marine Aspergillus niger
      was studied. The fungus was previously isolated from Gorgan Bay in the Caspian
      Sea. The kinetics of decolourization was studied by varying energy sources. The
      best decolourization was achieved when sucrose was used as source of carbon and
      energy. NH4+ ion was demonstrated to be the best nitrogen source. Color reduction
      was found to increase from 80-97% as inoculum concentration increased from 0.04
      1.0 g/L. A minimum inoculum of 0.2 g/L is necessary to achieve decolourization.
      The optimal temperature for the growth of A. niger on Baftkar wastewater is found
      to be 30 degrees C. 90-96% colour reduction is achieved in 19-20 hr of contact of
      mycelium cell with the wastewater. Colour reduction in a continuous column
      reactor of 70% was obtained using treated mycelium (NaOH, 90 degrees C) after 1
      hr.

PMID- 15248492
TI  - Performance of Spodoptera litura Fabricius on different host plants: influence of
      nitrogen and total phenolics of plants and mid-gut esterase activity of the
      insect.
AB  - Five host plants [castor, Ricinus communis (Carolus Linnaeus); cotton, Gossypium
      hirsutm (Carolus Linnaeus); tomato, Lycopersicum esculentum (Philip Miller);
      mint, Mentha arvensis (Carolus Linnaeus) and cabbage, Brassica oleracea (Carolus
      Linnaeus)] belonging to different families were used to study the performance of
      the Asian armyworm, Spodoptera litura larvae. Highest consumption of food and dry
      weight gain was observed in larvae fed on castor. Mint did not support optimum
      larval growth because of low digestibility and low efficiency of conversion of
      digested food to body matter. Dry weight gain ranged from 26.64 mg on mint to
      86.80 mg in castor. These differences tend to be related to nitrogen and total
      phenolics content of the leaf tissues; however, the most clear-cut correlation is
      an inverse one between the host plant preference and the ratio of total phenolics
      to nitrogen in the leaf tissues. Mid-gut esterase activity in larvae showed an
      increasing trend with the increase in total phenolics: nitrogen ratio in the test
      plants and the order of mid-gut esterase activity in larvae was mint > cabbage >
      cotton > tomato > castor.

PMID- 15248494
TI  - Performance of Uscana mukerjii (Mani) for the control of Callosobruchus maculatus
      (Fab.) and allied bruchid species.
AB  - Investigations have been carried out on the relative preference of U. mukerjii to
      four common species viz., C. maculatus, C. analis, C. chinensis and Zabrotes
      subfasciatus of store bruchids. Results show correspondence between the
      acceptance/contact ratio and the total number of eggs laid by the parasitoid for
      Callosobruchus species. U. mukerjii shows maximum preference on C. maculatus
      followed by C. analis, C. chinensis and Z. subfasciatus in the decreasing order.
      Z. subfasciatus has been the least preferred host having 2-3% parasitization in
      choice situation. Percentage emergence of the adults and females differ
      insignificantly from each other in Callosobruchus species. In no choice
      experiments, U. mukerjii laid sufficient number of eggs in the eggs of C.
      chinensis and Z. subfasciatus but less number of eggs in a choice situation due
      to competition with the preferred host. As is evident, U. mukerjii gives the
      first preference to primary host C. maculatus. Moreover, the congeneric species
      i.e C. analis and C. chinensis are given more preference than Z. subfasciatus.

PMID- 15248495
TI  - Validation of qualitative test for phosphine gas in human tissues.
AB  - Phosphine has been known to science since the birth of modern chemistry. WHO
      reports that the technical product usually has a foul odour, like "fishy" or
      "garlicky" because of the presence of substituted phosphines and diphosphine
      (P2H4). Many medico-legal autopsy cases have been reported positive for aluminium
      phosphide even though there was neither any suspicion of consuming aluminium
      phosphide nor any clinical findings, postmortem findings or circumstantial
      evidences. The present study was carried out to validate the qualitative test,
      presently applied in many laboratories for testing phosphine. It was observed
      that 65% of human tissues in saturated solution of common salt show positivity
      for phosphine gas on the first day of autopsy.

PMID- 15248496
TI  - Curing of symbiotic plasmid of Mesorhizobium huakuii subsp. rengei isolated from
      Astragalus sinicus.
AB  - Astragalus sinicus (Chinese Milk vetch), a green manure leguminous plant, harbors
      Mesorhizobium huakuii subsp. rengei strain B3 in the root nodules. The
      visualization of symbiotic plasmid of strain B3 showed the presence of one sym
      plasmid of about 425 kbp. Curing of sym plasmid by temperature and acrydine
      orange was studied. Growing rhizobial cells at high temperature (37 degrees C) or
      treating the cells with acrydine orange at 50 mg/l eliminated sym plasmid of M.
      huakuii strain B3, which was confirmed by sym plasmid visualization and plant
      infection test of cured strains.

PMID- 15248497
TI  - Inhibition of methanogenesis by interaction of aluminium ion with co-factor, F
      420, in Methanosarcina barkeri.
AB  - Methane emission was inhibited by aluminium ion in paddy fields. Addition of Al3+
      (20 mM) to the culture medium containing cells of pure Methanosarcina barkeri,
      inhibited methanogenesis. Methanogenic co-factor, F-420, was isolated and
      purified from Methanosarcina barkeri MS. Spectrophotometric and
      spectrofluorometric analysis of interaction between co-factor, F-420, and Al3+
      revealed that they formed a complex compound that might have blocked
      methanogenesis.

PMID- 15248498
TI  - Larval pupation site preference in a few species of Drosophila.
AB  - Larval pupation site preference (PSP) is an important event in preadult
      development. The PSP was studied on the basis of the number of larvae pupated at
      different sites in the cultures. The results revealed that the larval PSP in
      different species of Drosophila varies significantly at different sites. The
      sympatric species also differ in their PSP and the pupation behaviour does not
      correspond with the taxonomic relationship between the species.

PMID- 15248499
TI  - Impact of CdCl2 on biochemical changes in planaria, Dugesia bengalensis
      Kawakatsu.
AB  - Cadmium induces different anomalous behavioral changes with dose and time
      dependent mortality and change in the macromolecular patterns of D. bengalensis.
      Bio-accumulation of heavy metal in planarians could be used to detect the level
      of water pollution.

PMID- 15248500
TI  - A protocol for shoot multiplication from foliar meristem of Vanda spathulata (L.)
      Spreng.
AB  - Leaf explants collected from flowering plants of Vanda spathulata were cultured
      in Mitra medium with combinations of 6-benzyladenine (BA; 13.2-88.8 microM) and
      indole-3-acetic acid (IAA; 0.0 -85.6 microM). Combination of BA (66.6 microM) and
      IAA (28.5 microM) induced maximum shoots (17.33) from foliar meristems (leaf
      base). BA individually did not induce caulogenesis in leaf explants. For
      optimized multiplication, BA:IAA (2:1 microM) was essential at 22.2- 88.8 microM
      of BA. Re-cultured leaf explants produced lesser number of shoots compared to
      original explants and were nearly equal at combinations of 22.2-44.4 microM of BA
      and 5.7-28.5 microM of IAA. Rooting of shoots (> 95%) occurred in medium
      containing banana pulp (75 gl(-1)) and IAA (5.7 microM) within 3-9 weeks.
      Plantlets with 2-5 roots of 2-5 cm length established easily in community pots at
      80-90% rates without hardening.

PMID- 15248501
TI  - Estrogens: from classical endocrine action to tissue selective action.

PMID- 15248502
TI  - Identification of RIP140 as a nuclear receptor cofactor with a role in female
      reproduction.

PMID- 15248503
TI  - A structural explanation for ERalpha/ERbeta SERM discrimination.
AB  - Many NRs have multiple subtypes that possess distinct expression patterns and
      that regulate distinct target genes. Antagonists generated through the addition
      of bulky side chains to agonist scaffolds are limited to being antagonistic on
      one or more subtypes of a particular NR. The passive antagonism mechanism, as
      revealed in our studies through direct comparison of the two THC-ER LBD
      complexes, suggests a new approach to achieving NR antagonism. Compounds could be
      designed to selectively stabilize the inactive conformations of certain NR
      subtypes and the active conformations of others. Such ligands are likely to exert
      novel biological and therapeutic effects.

PMID- 15248504
TI  - Protein structure-based design, synthesis strategy and in vitro pharmacological
      characterization of estrogen receptor alpha and beta selective compounds.

PMID- 15248505
TI  - How to understand estrogen signaling from the phenotypes of ERalpha and ERbeta
      knockout mice.

PMID- 15248506
TI  - Mechanisms of estrogenic effects on neurobiological functions.

PMID- 15248507
TI  - Role of estrogens in the male reproductive tract.

PMID- 15248508
TI  - Are estrogens of importance to ovarian function?

PMID- 15248509
TI  - Biological effects of ERalpha- and ERbeta-selective estrogens.

PMID- 15248510
TI  - The ERE-luc reporter mouse.

PMID- 15248511
TI  - Role of estrogens in ovarian dysfunction and fertility. Options for new therapies
      with SERMs.

PMID- 15248512
TI  - Estrogens and atherosclerosis.

PMID- 15248513
TI  - Hormone replacement (therapy): a time for interrogation, information and further
      studies.

PMID- 15248514
TI  - Molecular imaging: dream or reality?

PMID- 15248515
TI  - Target discovery and validation.

PMID- 15248516
TI  - Noninvasive imaging in drug discovery and development.

PMID- 15248517
TI  - Internal dose assessment--extrapolation from animal species to the human.

PMID- 15248518
TI  - PET for drug development.

PMID- 15248519
TI  - Future directions in molecular imaging.

PMID- 15248520
TI  - Regulatory implication--the EU perspective.

PMID- 15248521
TI  - Nonclinical development of radiopharmaceuticals: regulatory considerations for
      the United States Food and Drug Administration.

PMID- 15248522
TI  - The Japanese perspective on radiopharmaceuticals.

PMID- 15248523
TI  - At a glance: HIV/AIDS surveillance to 31 December, 2003.

PMID- 15248524
TI  - An introductory letter in advance of a telephone survey may increase response
      rate.

PMID- 15248525
TI  - Modeling of noninvasive microwave characterization of breast tumors.
AB  - This paper describes an approach for the noninvasive microwave characterization
      of tumors in breast tissue. Tumors are modeled as lossy dielectric targets. Their
      complex natural resonances (CNR) can be extracted from the time-domain response
      and correlated with diagnostically useful properties. Finite-difference time
      domain simulation is used to obtain the time-domain response from a tumor with a
      short electromagnetic pulse as an input. The normal breast tissue and tumor are
      modeled as dispersive media using the Debye model and CNRs are extracted using
      Prony's method. It is shown that the locations of the dominant CNRs are separated
      in the complex frequency plane as functions of the tumor dielectric properties.
      The technique has potential as a diagnostic tool to characterize breast lesions
      in conjunction with other imaging modalities such as ultrasound for detection.

PMID- 15248526
TI  - The Goodman-Kruskal coefficient and its applications in genetic diagnosis of
      cancer.
AB  - Increasing interest in new pattern recognition methods has been motivated by
      bioinformatics research. The analysis of gene expression data originated from
      microarrays constitutes an important application area for classification
      algorithms and illustrates the need for identifying important predictors. We show
      that the Goodman-Kruskal coefficient can be used for constructing minimal
      classifiers for tabular data, and we give an algorithm that can construct such
      classifiers.

PMID- 15248527
TI  - A model of the rat phrenic motor neuron.
AB  - We have developed a model for the rat phrenic motor neuron (PMN) that robustly
      replicates many experimentally observed behaviors of PMNs in response to
      pharmacological, ionic, and electrical perturbations using a single set of
      parameters. Our model suggests that the after-depolarization (ADP) response seen
      in action potentials is a result of the slow deactivation of the fast sodium
      channel in the range of the ADP coupled with the activation of the L-type calcium
      channel (I(CaL)). This current and its interactions with the small and large
      conductance calcium-activated potassium currents (I(KCaSK) and I(KCaBK),
      respectively) is also important in the generation of spike frequency adaptation
      in the repetitive firing mode of activity. Other aspects of the model conform
      very well to experimental observations in both the action potential and
      repetitive firing mode of activity, including the role of I(KCaSK) in the medium
      after-hyperpolarization (AHP) and the role of I(KCaBK) in the fast AHP. We have
      made a number of predictions using the model, including the characterization of
      two putative sodium currents (fast and persistent), as well as functional roles
      for the N- and T-type calcium currents.

PMID- 15248528
TI  - Opioid-induced respiratory depression: a mathematical model for fentanyl.
AB  - In this paper, respiratory depressant effects of fentanyl are described
      quantitatively by a mathematical model. The model is an extension of a previous
      one, which reproduces the human ventilatory control system on a physiological
      basis. It includes the following: three compartments for gas storage and exchange
      (lungs, body tissue, and brain tissue); the main mechanisms involved in
      ventilation control (peripheral chemoreceptors, central chemoreceptors, and the
      central hypoxic depression); and local blood flow regulation. The effects of
      fentanyl on the respiratory system include a decrease in peripheral and central
      chemoreceptor gains on ventilation and a direct inhibition of respiratory neural
      activity. All parameters in the model were chosen according to the literature.
      The model is able to reproduce the ventilatory effects of fentanyl in several
      conditions: 1) constant levels of fentanyl; 2) after a bolus injection; 3) at
      fixed levels of P(ETCO2); and 4) after artificial ventilation. According to the
      model, in spontaneously breathing subjects, minute ventilation depends on two
      opposing actions: fentanyl inhibitory influences, which depress ventilation,
      reducing oxygen tension and increasing CO2 tension, and the consequent activation
      of chemoreceptors, which stimulates ventilation. Simulations of anesthetized
      patients resuming spontaneous breathing after artificial ventilation demonstrate
      the risk of prolonged apnea and tissue hypoxemia. A safe transition can be
      achieved by increasing patient PCO2 toward the end of artificial ventilation,
      because an advanced chemoreceptor stimulation is produced, which promptly
      counteracts fentanyl-induced inhibition at cessation of artificial ventilation.

PMID- 15248529
TI  - Projective filtering of time-aligned ECG beats.
AB  - A method of electrocardiographic (ECG) signal processing developed by
      introduction of time synchronization into the method of nonlinear state-space
      projections is presented. It can be regarded as an extension of time averaging
      but contrary to usual averaging it preserves variability of ECG beats morphology.
      For this purpose, after the respective beats time alignment, the synchronized
      intervals of the signal undergo processing according to the rules of principal
      component analysis (PCA). PCA allows for determination of orthogonal basis
      functions which can be employed for approximation of the respective intervals.
      The operation is aimed to retain the deviations from the mean which result from
      the desired component changes and to reject the deviations caused by noise. The
      method's capabilities are investigated and some of its applications are
      presented.

PMID- 15248530
TI  - A matrix-based algorithm for estimating multiple coherence of a periodic signal
      and its application to the multichannel EEG during sensory stimulation.
AB  - The coherence between the stimulation signal and the electroencephalogram (EEG)
      has been used in the detection of evoked responses. The detector's performance,
      however, depends on both the signal-to-noise ratio (SNR) of the responses and the
      number of data segments (M) used in coherence estimation. In practical
      situations, when a given SNR occurs, detection can only be improved by increasing
      M and hence the total data length. This is particularly relevant when monitoring
      is the objective. In the present study, we propose a matrix-based algorithm for
      estimating the multiple coherence of the stimulation signal taking into account a
      set of N EEG channels as a way of increasing the detection rate for a fixed value
      of M. Monte Carlo simulations suggest that thresholds for such multivariate
      detector are the same as those for multiple coherence of Gaussian signals and
      that using more than six signals is not advisable for improving the detection
      rate with M = 10. The results with EEG from 12 normal subjects during photic
      stimulation at 10 Hz showed a maximum detection for N greater than 2 in 58% of
      the subjects with M = 10, and hence suggest that the proposed multivariate
      detector is valuable in evoked responses applications.

PMID- 15248531
TI  - Objective detection of the central auditory processing disorder: a new machine
      learning approach.
AB  - The objective detection of binaural interaction is of diagnostic interest for the
      evaluation of the central auditory processing disorder (CAPD). The beta-wave of
      the binaural interaction component in auditory brainstem responses has been
      suggested as an objective measure of binaural interaction and has been shown to
      be of diagnostic value in the CAPD diagnosis. However, a reliable and automated
      detection of the beta-wave capable of clinical use still remains a challenge. We
      propose a new machine learning approach to the detection of the CAPD that is
      based on adapted tight frame decompositions which are tailored for support vector
      machines with radial kernels. Using shift-invariant scale and morphological
      features of the binaurally evoked brainstem potentials, our approach provides at
      least comparable results to the beta-wave detection in view of the discrimination
      of subjects being at risk for CAPD and subjects being not at risk for CAPD.
      Furthermore, as no information from the monaurally evoked potentials is
      necessary, the measurement cost is reduced by two-thirds compared to the
      computation of the binaural interaction component. We conclude that a machine
      learning approach in the form of a hybrid tight frame-support vector
      classification is effective in the objective detection of the CAPD.

PMID- 15248532
TI  - Surrogate data analysis for assessing the significance of the coherence function.
AB  - In cardiovascular variability analysis, the significance of the coupling between
      two time series is commonly assessed by setting a threshold level in the
      coherence function. While traditionally used statistical tests consider only the
      parameters of the adopted estimator, the required zero-coherence level may be
      affected by some features of the observed series. In this study, three
      procedures, based on the generation of surrogate series sharing given properties
      with the original but being structurally uncoupled, were considered: independent
      identically distributed (IID), Fourier transform (FT), and autoregressive (AR).
      IID surrogates maintained the distribution of the original series, while FT and
      AR surrogates preserved the power spectrum. The ability of the three methods to
      define the threshold for zero coherence was validated and compared by computer
      simulations reproducing typical cardiovascular interactions. While the IID
      threshold depended only on record length and design parameters of the coherence
      estimator, FT and AR thresholds were frequency-dependent with peaks corresponding
      to the local maxima of the estimated coherence. FT and AR surrogates were able to
      compensate spurious coherence peaks due to equal-frequency but independent
      oscillations in the two series. The benefit of frequency-dependent thresholds was
      evident for short series with narrow-band oscillations. Thus, surrogates
      preserving the power spectrum of the original series are recommended to avoid
      false coupling detections in the presence of oscillations occurring at nearby
      frequencies but produced by different mechanisms, as may frequently happen in
      cardiovascular and cardiorespiratory regulation.

PMID- 15248533
TI  - On the statistical significance of event-related EEG desynchronization and
      synchronization in the time-frequency plane.
AB  - We propose and discuss a complete framework for estimating significant changes in
      the average time-frequency density of energy of event-related signals. Addressed
      issues include estimation of time-frequency energy density (matching pursuit and
      spectrogram), choice of resampling statistics to test the hypothesis of change in
      one small region (resel), and correction for multiplicity (false discovery rate).
      We present estimation of the significance of event-related electroencephalograph
      desynchronization and synchronization (ERD/ERS) in the time-frequency plane.

PMID- 15248534
TI  - Atrial activity extraction for atrial fibrillation analysis using blind source
      separation.
AB  - This contribution addresses the extraction of atrial activity (AA) from real
      electrocardiogram (ECG) recordings of atrial fibrillation (AF). We show the
      appropriateness of independent component analysis (ICA) to tackle this biomedical
      challenge when regarded as a blind source separation (BSS) problem. ICA is a
      statistical tool able to reconstruct the unobservable independent sources of
      bioelectric activity which generate, through instantaneous linear mixing, a
      measurable set of signals. The three key hypothesis that make ICA applicable in
      the present scenario are discussed and validated: 1) AA and ventricular activity
      (VA) are generated by sources of independent bioelectric activity; 2) AA and VA
      present non-Gaussian distributions; and 3) the generation of the surface ECG
      potentials from the cardioelectric sources can be regarded as a narrow-band
      linear propagation process. To empirically endorse these claims, an ICA algorithm
      is applied to recordings from seven patients with persistent AF. We demonstrate
      that the AA source can be identified using a kurtosis-based reordering of the
      separated signals followed by spectral analysis of the sub-Gaussian sources. In
      contrast to traditional methods, the proposed BSS-based approach is able to
      obtain a unified AA signal by exploiting the atrial information present in every
      ECG lead, which results in an increased robustness with respect to electrode
      selection and placement.

PMID- 15248535
TI  - Reduction of stimulus artifact in somatosensory evoked potentials: segmented
      versus subthreshold training.
AB  - A new approach to stimulus artifact cancellation is introduced, which attempts to
      model the process of stimulus artifact generation. This is done by training an
      estimator with multiple exemplars of the stimulus artifact at levels below the
      threshold of evoked response stimulation. Two estimators are formulated: one
      using a dynamic neural network and another using a linear estimator. The
      performance of these new approaches is compared to the segmented training
      approach, which has been previously demonstrated to be one of the most capable
      methods available. Performance assessment is carried out using a novel metric
      introduced in this paper, which focuses upon the relevant portion of the recorded
      waveform. The new cancellation schemes show distinct performance advantages over
      the segmented training approach.

PMID- 15248536
TI  - Automatic classification of heartbeats using ECG morphology and heartbeat
      interval features.
AB  - A method for the automatic processing of the electrocardiogram (ECG) for the
      classification of heartbeats is presented. The method allocates manually detected
      heartbeats to one of the five beat classes recommended by ANSI/AAMI EC57:1998
      standard, i.e., normal beat, ventricular ectopic beat (VEB), supraventricular
      ectopic beat (SVEB), fusion of a normal and a VEB, or unknown beat type. Data was
      obtained from the 44 nonpacemaker recordings of the MIT-BIH arrhythmia database.
      The data was split into two datasets with each dataset containing approximately
      50,000 beats from 22 recordings. The first dataset was used to select a
      classifier configuration from candidate configurations. Twelve configurations
      processing feature sets derived from two ECG leads were compared. Feature sets
      were based on ECG morphology, heartbeat intervals, and RR-intervals. All
      configurations adopted a statistical classifier model utilizing supervised
      learning. The second dataset was used to provide an independent performance
      assessment of the selected configuration. This assessment resulted in a
      sensitivity of 75.9%, a positive predictivity of 38.5%, and a false positive rate
      of 4.7% for the SVEB class. For the VEB class, the sensitivity was 77.7%, the
      positive predictivity was 81.9%, and the false positive rate was 1.2%. These
      results are an improvement on previously reported results for automated heartbeat
      classification systems.

PMID- 15248537
TI  - Fetal MEG redistribution by projection operators.
AB  - The fetal magnetoencephalogram (fMEG) is measured in the presence of large
      interference from the maternal and fetal magnetocardiograms. This interference
      can be efficiently attenuated by orthogonal projection of the corresponding
      spatial vectors. However, the projection operators redistribute the fMEG signal
      among sensors. Although redistribution can be readily accounted for in the
      forward solution, visual interpretation of the fMEG signal topography is made
      difficult. We have devised a general, model-independent method for correction of
      the redistribution effect that utilizes the assumption that we know in which
      channels the fMEG should be negligible (such channels are distant from the known
      fetal head position). In a simplified case where the fMEG can be explained by
      equivalent current dipoles, the correction can also be obtained from fitting the
      dipoles to the fMEG signal. The corrected fMEG signal topography then corresponds
      to the dipole forward solution, but without orthogonal projection. We illustrate
      the redistribution correction on an example of experimentally measured flash
      evoked fMEG.

PMID- 15248538
TI  - Three-dimensional surface reconstruction and panoramic optical mapping of large
      hearts.
AB  - Optical mapping of electrical activity from the surface of the heart is a
      powerful tool for studying complex arrhythmias. However, a limitation of
      traditional optical mapping is that the mapped region is restricted to the field
      of view of the sensor, which makes it difficult to track electrical waves as they
      drift in and out of view. To address this, we developed an optical system that
      panoramically maps epicardial electrical activity in three dimensions. The system
      was engineered to accomodate hearts comparable in size to human hearts. It is
      comprised of a surface scanner that measures epicardial geometry and a panoramic
      fluorescence imaging system that records electrical activity. Custom software
      texture maps the electrical data onto a reconstructed epicardial surface. The
      result is a high resolution, spatially contiguous, mapping dataset. In addition,
      the three-dimensional positions of the recording sites are known, making it
      possible to accurately measure parameters that require geometric information,
      such as propagation velocity. In this paper, we describe the system and
      demonstrate it by mapping a swine heart.

PMID- 15248539
TI  - Surface alignment of an elastic body using a multiresolution wavelet
      representation.
AB  - An algorithm for nonlinear registration of an elastic body is developed. Surfaces
      (outlines) of known anatomic structures are used to align all other (internal)
      points. The deformation field is represented with a multiresolution wavelet
      expansion and is modeled by the partial differential equations of linear
      elasticity. A hierarchical approach that reduces algorithm complexity is adopted.
      The performance of the algorithm is evaluated by two-dimensional alignment of
      sections from mouse brains located in the olfactory bulbs. The registration
      algorithm was guided by manually delineated contours of a subset of brain
      structures and validated based on another subset of brain structures. The wavelet
      alignment algorithm produced a twofold to fivefold improvement in accuracy over
      an affine (linear) alignment algorithm.

PMID- 15248540
TI  - A novel electrode array for diameter-dependent control of axonal excitability: a
      simulation study.
AB  - Electrical extracellular stimulation of peripheral nerve activates the large
      diameter motor fibers before the small ones, a recruitment order opposite the
      physiological recruitment of myelinated motor fibers during voluntary muscle
      contraction. Current methods to solve this problem require a long-duration
      stimulus pulse which could lead to electrode corrosion and nerve damage. The
      hypothesis that the excitability of specific diameter fibers can be suppressed by
      reshaping the profile of extracellular potential along the axon using multiple
      electrodes is tested using computer simulations in two different volume
      conductors. Simulations in a homogenous medium with a nine-contact electrode
      array show that the current excitation threshold (Ith) of large diameter axons
      (13-17 microm) (0.6-3.0 mA) is higher than that of small-diameter axons (2-7
      microm) (0.4-0.7 mA) with 200-microm axon-electrode distance and 10-micros
      stimulus pulse. The electrode array is also tested in a three-dimensional finite
      element model of the sacral root model of dog (ventral root of S3). A single
      cathode activates large-diameter axons before activating small axons. However, a
      nine-electrode array activates 50% of small axons while recruiting only 10% of
      large ones and activates 90% of small axons while recruiting only 50% of large
      ones. The simulations suggest that the near-physiological recruitment order can
      be achieved with an electrode array. The diameter selectivity of the electrode
      array can be controlled by the electrode separation and the method is independent
      of pulse width.

PMID- 15248541
TI  - On the flow dependency of the electrical conductivity of blood.
AB  - Experiments presented in the literature show that the electrical conductivity of
      flowing blood depends on flow velocity. The aim of this study is to extend the
      Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles
      in an electrolyte, to explain this flow dependency of the conductivity of blood
      for stationary laminar flow in a rigid cylindrical tube. Furthermore, these
      theoretical results are compared to earlier published measurement results. To
      develop the theory, we assumed that blood is a Newtonian fluid and that red blood
      cells can be represented by oblate ellipsoids. If blood flows through a
      cylindrical tube, shear stresses will deform and align the red blood cells with
      one of their long axes aligned parallel to the stream lines. The pathway of a low
      frequency (< 1 MHz) alternating electrical current will be altered by this
      orientation and deformation of the red blood cells. Consequently, the electrical
      conductivity in the flow direction of blood increases. The theoretically
      predicted flow dependency of the conductivity of blood corresponds well with
      experimental results. This theoretical study shows that red blood cell
      orientation and deformation can explain quantitatively the flow dependency of
      blood conductivity.

PMID- 15248542
TI  - Microdynamics of the piezo-driven pipettes in ICSI.
AB  - Undesirably low success rates have been reported in the intracytoplasmic sperm
      injection procedure. Recently a method using piezo-driven pipettes with a very
      small mercury column contributed substantial improvements in this process.
      Despite the toxicity of mercury, this new procedure is commonly utilized in many
      laboratories. However, there is no study available to date on the micromechanics
      of this procedure. The underlying principles of piercing are not clear for both
      cases, with and without the mercury. Presently, the pressure burst, which is
      caused by the abrupt axial motion of the mercury column, is attributed to this
      effect. Here, we take the mercury-filled pipettes and try to understand the
      governing physics. The findings point out the occurrence of considerable lateral
      tip oscillations of the injection pipette as the piezoelectric pulse train is
      introduced. We claim that the lateral dynamics play an important role in the
      piercing and should be considered to enlighten the process and the effects of the
      mercury. These claims are analytically studied and experimentally verified.

PMID- 15248543
TI  - Using wavelet transform and fuzzy neural network for VPC detection from the
      Holter ECG.
AB  - A novel method for detecting ventricular premature contraction (VPC) from the
      Holter system is proposed using wavelet transform (WT) and fuzzy neural network
      (FNN). The basic ideal and major advantage of this method is to reuse information
      that is used during QRS detection, a necessary step for most ECG classification
      algorithm, for VPC detection. To reduce the influence of different artifacts, the
      filter bank property of quadratic spline WT is explored. The QRS duration in
      scale three and the area under the QRS complex in scale four are selected as the
      characteristic features. It is found that the R wave amplitude has a marked
      influence on the computation of proposed characteristic features. Thus, it is
      necessary to normalize these features. This normalization process can reduce the
      effect of alternating R wave amplitude and achieve reliable VPC detection. After
      normalization and excluding the left bundle branch block beats, the accuracies
      for VPC classification using FNN is 99.79%. Features that are extracted using
      quadratic spline wavelet were used successfully by previous investigators for QRS
      detection. In this study, using the same wavelet, it is demonstrated that the
      proposed feature extraction method from different WT scales can effectively
      eliminate the influence of high and low-frequency noise and achieve reliable VPC
      classification. The two primary advantages of using same wavelet for QRS
      detection and VPC classification are less computation and less complexity during
      actual implementation.

PMID- 15248544
TI  - A density-based cellular automaton model for studying the clustering of
      noninvasive cells.
AB  - We investigated whether cluster formation by noninvasive cells can be explained
      by a global attractive potential. Indices quantifying the persistence of
      migration in experimental conditions were compared to the same indexes computed
      from simulations with a density-based cellular automaton. The results indicate
      that the attractive potential hypothesis must be rejected.

PMID- 15248545
TI  - Effect of skull resistivity on the spatial resolutions of EEG and MEG.
AB  - The resistivity values of the different tissues of the head affect the lead
      fields of electroencephalography (EEG). When the head is modeled with a
      concentric spherical model, the different resistivity values have no effect on
      the lead fields of the magnetoencephalography (MEG). Recent publications indicate
      that the resistivity of the skull is much lower than what was estimated by Rush
      and Driscoll. At the moment, this information on skull resistivity is, however,
      slightly controversial. We have compared the spatial resolution of EEG and MEG
      for cortical sources by calculating the half-sensitivity volumes (HSVs) of EEG
      and MEG as a function of electrode and magnetometer distance, respectively, with
      the relative skull resistivity as a parameter. Because the spatial resolution is
      related to the HSV, these data give an overview of the effect of these parameters
      on the spatial resolution of both techniques. Our calculations show that, with
      the new information on the resistivity of the skull, in the spherical model for
      cortical sources the spatial resolution of the EEG is better than that of the
      MEG.

PMID- 15248546
TI  - Computationally effective algorithm for robust weighted averaging.
AB  - One of the greatest disadvantages of the weighted signal averaging method is its
      sensitivity to the presence of noise and outliers in data and the need to
      estimate the noise variance in all signal cycles. The robust weighted averaging
      method based on the epsilon-insensitive loss function is free of these
      disadvantages, but has a very high computational burden and requires a choice of
      the insensitivity parameter epsilon. In this study, a new computationally
      effective algorithm for robust weighted averaging with automatic adjustment of
      the insensitivity parameter is introduced.

PMID- 15248547
TI  - Assessing blood flow control through a bootstrap method.
AB  - In order to assess blood flow control, the relationship between blood pressure
      and blood flow can be modeled by linear filters. We present a bootstrap method,
      which allows the statistical analysis of an index of blood flow control that is
      obtained from constrained system identification using an established set of pre
      defined filters.

PMID- 15248548
TI  - A computer-aided diagnosis for distinguishing Tourette's syndrome from chronic
      tic disorder in children by a fuzzy system with a two-step minimization approach.
AB  - Tourette's syndrome, no longer considered as a rare and unusual disease, is the
      most severe tic disorder in children. Early differential diagnosis between
      Tourette's syndrome and chronic tic disorder is difficult but important because
      proper and early medical therapy can improve the child's condition. Brain single
      photon emission computed tomography (SPECT) perfusion imaging with technetium-99m
      hexamethylpropylene amine oxime is a method to distinguish these two diseases. In
      this paper, a fuzzy system called characteristic-point-based fuzzy inference
      system (CPFIS) is proposed to help radiologists perform computer-aided diagnosis
      (CAD). The CPFIS consists of SPECT-volume processing, input-variables selection,
      characteristic-points (CPs) derivation, and parameter tuning of the fuzzy system.
      Experimental results showed that the major fuzzy rules from the obtained CPs
      match the major patterns of Tourette's syndrome and chronic tic disorder in
      perfusion imaging. If any case that was diagnosed as chronic tic by the
      radiologist but as Tourette's syndrome by the CPFIS was taken as Tourette's
      syndrome, then the accuracy of the radiologist was increased from 87.5% (21 of
      24) without the CPFIS to 91.7% (22 of 24) with the CPFIS. All 17 cases of
      Tourette's syndrome, which is more severe than chronic tic disorder, were
      correctly classified. Although the construction and application process of the
      proposed method is complete, more samples should be used and tested in order to
      design a universally effective CAD without small sample-size concerns in this
      research.

PMID- 15248549
TI  - Fractional calculus in bioengineering.
AB  - Fractional calculus (integral and differential operations of noninteger order) is
      not often used to model biological systems. Although the basic mathematical ideas
      were developed long ago by the mathematicians Leibniz (1695), Liouville (1834),
      Riemann (1892), and others and brought to the attention of the engineering world
      by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on
      the topic was published by Oldham and Spanier. Recent monographs and symposia
      proceedings have highlighted the application of fractional calculus in physics,
      continuum mechanics, signal processing, and electromagnetics, but with few
      examples of applications in bioengineering. This is surprising because the
      methods of fractional calculus, when defined as a Laplace or Fourier convolution
      product, are suitable for solving many problems in biomedical research. For
      example, early studies by Cole (1933) and Hodgkin (1946) of the electrical
      properties of nerve cell membranes and the propagation of electrical signals are
      well characterized by differential equations of fractional order. The solution
      involves a generalization of the exponential function to the Mittag-Leffler
      function, which provides a better fit to the observed cell membrane data. A
      parallel application of fractional derivatives to viscoelastic materials
      establishes, in a natural way, hereditary integrals and the power law
      (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In
      this review, I will introduce the idea of fractional operations by following the
      original approach of Heaviside, demonstrate the basic operations of fractional
      calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering
      interest, and give specific examples from electrochemistry, physics,
      bioengineering, and biophysics. The fractional derivative accurately describes
      natural phenomena that occur in such common engineering problems as heat
      transfer, electrode/electrolyte behavior, and sub-threshold nerve propagation. By
      expanding the range of mathematical operations to include fractional calculus, we
      can develop new and potentially useful functional relationships for modeling
      complex biological systems in a direct and rigorous manner.

PMID- 15248550
TI  - A meaningless gesture.

PMID- 15248551
TI  - Heal the law, then health care.

PMID- 15248552
TI  - Musing on health and grass.

PMID- 15248553
TI  - The health disparities gap.

PMID- 15248554
TI  - Washington house call.

PMID- 15248555
TI  - Medicaid HMOs or PCCM?

PMID- 15248556
TI  - Taking calls.

PMID- 15248557
TI  - You can observe a lot by watching.

PMID- 15248558
TI  - The medical cost of high serum cholesterol in Harris County, Texas.
AB  - High serum cholesterol levels are common among Texans, especially in the greater
      Houston metropolitan area (Harris County) where such levels are almost 50% higher
      than the national norm. By using actual medical care claims and cost data, an
      analysis was conducted to determine the direct medical care cost of high serum
      cholesterol tied to selected cardiovascular conditions in Harris County. As part
      of conducting the analysis, Health Management Associates obtained prevalence
      rates of Harris County residents with elevated cholesterol levels, actual
      inpatient cardiovascular claims and costs, and estimated outpatient
      cardiovascular claims and costs. The financial cost analysis of high cholesterol
      revealed that more than 25 million dollars was spent alone on selected
      cardiovascular conditions. This estimate is conservative because it did not
      factor in all types of cardiovascular claims associated with high serum
      cholesterol, did not factor in other (noncardiovascular) claims that may be
      associated with high serum cholesterol, and did not include indirect costs such
      as absenteeism, lost productivity, and medication costs associated with the
      selected conditions. As Harris County is home to approximately 1 of every 5
      adults in Texas, extrapolating the county's direct costs for high serum
      cholesterol to the entire state would translate into a direct medical care tab of
      more than 120 million dollars.

PMID- 15248559
TI  - Morphometric analyses of axons in the human lateral corticospinal tract:
      cervical/lumbar level comparison and relation to the ageing process.
AB  - Myelinated axons in the human lateral corticospinal tract (LCST) at the C6 and L4
      levels were examined on 16 male cadavers, with age ranging from 41 to 88 years.
      The average area of axons in the LCST was measured using a microscopic image
      analyzing system. Our data show that the average area of axons at the C6 and L4
      levels decreased with age. We also noticed that the average area of axons was
      larger at the C6 level than at the L4 level in all cases. This decrease may be
      related to a parallel decrease of conduction velocity in the LCST during the
      ageing process.

PMID- 15248560
TI  - A morphological study on the classification of maxillary dental arches.
AB  - To evaluate the morphology of dental arches, 62 (male: 36, female: 26) paired
      casts having normal dentitions and occlusion were selected from 396 (age: 18 to
      26 years old; male: 257, female: 139) sets of dental study models. The maxillary
      dentitions were preliminarily classified as square, round-square, round and round
      V-shaped arches based on the conventional morphological descriptions. Midpoints
      of the incisor edge (I1(R), I1(L), I2(R), & I2(L), summits of the cuspids (CR &
      CL), buccal cusps of the premolars (P1(R), P1(L), P2(R), & P2L), mesial buccal
      cusps of the first and second molars (M1(R), M1(L), M2(R), & M2(L)), and the
      midpoint (A) of line I1(R)-I1(L) were designated as reference points. From A, let
      a vertical line intersected line M2(R)-M2(L) at reference point B. The line A-B
      intersected C(R)-C(L) at reference point E. We evaluated 1) the protrusion of the
      cuspids by (1) angle I2(R)-C(R)-P1(R) (angle R) + angle I2(L)-C(L)-P1(L) (angle
      L); 2) the curvature of the anterior teeth by (2) A-B/C(R)-C(L), (3) 180 degrees 
      angle C(R)-A-C(L), and (4) A-E/C(R)-C(L); 3) the length to width ratio of the
      dental arch by (5) A-B/M2(R)-M2(L); 4) the degree of roundness of the maxillary
      arch by estimation of (6) (rtheta5 - rtheta4)R + (rtheta5 - rtheta4)L; and 5) an
      item (7) for the differentiation of type I and type II round-square arches by
      relating the bilateral contour and position of break line P1-P2-M1-M2 (i) to line
      P1-M2 (ii). The data of items (1), (2), (3), (4), (5), and (6) were further
      standardized and summarized into three essential principal components: 1) the
      curvature of the anterior teeth, 2) the curvilinear contour of the dental arch,
      and 3) the length-to-width ratio of the dental arch. The results indicated that:
      1) 60% of the maxillary dentitions were round-square arches which showed no
      prominent principal component; 2) square maxillary arches distinctly showed a
      small (1) angle R + angle L; 3) round arches were characteristic by small (6)
      (rtheta5 - rtheta4)R + (rtheta5 - rtheta4)L values; and 4) round V-shaped arches
      had large (1), (3) and (4) values.

PMID- 15248561
TI  - Postnatal development of multivesicular nuclear body in the Shiba goat Sertoli
      cell: an ultrastructural study.
AB  - The multivesicular nuclear body (MNB) within the Sertoli cell nucleolus has been
      observed in the ruminant testis, but not in other mammalian species. Generally,
      the MNB is composed of vesicles, tubules and ribosome-like structures. This study
      has been conducted in order to clarify MNB formation during postnatal
      development. The testes were obtained from immature Shiba goats at 1, 2, 3, 4,
      and 5 months old, and from adults. They were fixed with 5% glutaraldehyde,
      postfixed with 1% OsO4, dehydrated in ethanol and embedded in Araldite-M. The
      serial cross-sections of seminiferous tubules were morphologically and
      morphometrically observed using light and transmission electron microscopy. In
      these Shiba goat testes, the MNB contained vesicles and tubules in various sizes,
      as well as ribosome-like structures. The volume of each Sertoli cell nucleus at
      each age (1, 2, 3, 4, 5 months old and adult) was about 269.3 microm3, 327.1
      microm3, 361.3 microm3, 431.2 microm3, 525.0 microm3, and 760.4 microm3,
      respectively. The average number of vesicles per Sertoli cell nucleus was 0, 7.4,
      11.1, 12.3, 15.5, and 32.7, respectively. At 1 month old, one or more nucleoli
      with fibrillar components were identified in the Sertoli cell nucleus. No MNB was
      observed. At 2 months old, a MNB first appeared, though it was underdeveloped and
      infrequently encountered. At this stage, a MNB, consisting of a small amount of
      vesicles and ribosomes, was located in the peripheral region of the nucleus. At
      later stages (3, 4, and 5 months old), MNBs gradually developed, increased in
      number, moved from the periphery to the central region of the nucleus, and
      associated with the nucleus to form a well-developed MNB. In the adults, the
      Sertoli cell nucleus displayed a well-developed and large-sized MNB situated in
      the central region.

PMID- 15248562
TI  - Fine structure of the anal tonsilliar epithelium in the laboratory shrew (Suncus
      murinus).
AB  - The epithelium of the anal tonsil of the laboratory shrew was studied by scanning
      and transmission electron microscopy, with particular attention focused on the
      structure of the epithelium lining the anal tonsillar crypt. The tonsillar crypt
      surface is lined by two kinds of epithelia: squamous epithelium, which is located
      mainly at the neck of the crypt and includes keratohyalin granules in the
      superficial layer, and reticular epithelium, which is invaded by many immigrating
      cells and has several micropores immigrating cells to pass through. In addition,
      basal granulated cells are present in the basal layer. These results suggest that
      the reticular epithelium of the anal tonsil belongs to the well-developed gut
      associated lymphoid tissue (GALT) in the alimentary canal. It represents a
      specialized and important compartment in immunological function, similarly to the
      palatine tonsils of other mammals, and has as yet unknown roles in digestion.

PMID- 15248563
TI  - Sensory-motor cortex activity modulation by hypnotic susceptibility and hypnosis
      during finger movement.
AB  - The aim of the experiment was to study whether the activity of the primary
      sensory-motor (S1/M1), supplementary motor (SMA) and pre-motor (PMA) areas during
      fingers movement is modulated by hypnotic susceptibility and hypnosis. Cortical
      activity was studied through functional Magnetic Resonance Imaging (fMRI) during
      a finger-to-thumb opposition task in awake (Highs) and hypnotized highly
      susceptible (H-Highs) as well as in awake non susceptible subjects (Lows).
      Results did not show any significant difference in sensory-motor areas activation
      between Highs and Lows (trait effect) and between Highs and H-Highs (state
      effect). The activation in 3 subjects among Highs and only 1 among Lows (out of
      5) of the caudal S1, receiving the most part of the cutaneous input, appears
      noteworthy and prompts further investigation on possible hypnotizability-related
      differences in sensory-motor integration.

PMID- 15248564
TI  - The effect of preconditioning on the iron deposition after transient forebrain
      ischemia in rat brain.
AB  - In this study we investigated iron deposition in the hippocampus CA1 area and the
      corpus striatum pars dorsolateralis in a rat model of cerebral ischemia and
      ischemic tolerance. Forebrain ischemia was induced by four-vessel occlusion for 5
      min as ischemic preconditioning. Two days after the preconditioning or the sham
      operation, a second ischemia was induced for 20-min. With the use of iron
      histochemistry, regional changes were examined after 2 to 8 weeks of
      recirculation following the 20-min ischemia with or without preconditioning.
      Perl's reaction with DAB intensification demonstrated iron deposits in the CA1
      area and in the corpus striatum pars dorsolateralis after 2 weeks of
      recirculation. These iron deposits gradually increased in density and formed
      clusters by the 8th week. When the rats were exposed to 5-min ischemia 2 days
      before lethal 20-min ischemia, the deposition of iron in the CA1 region of the
      hippocampus and also in the corpus striatum pars dorsolateralis was decreased and
      produced a minimal number of iron-containing cells between the second and the 8th
      week of recirculation. Preconditioning with sublethal 5-min ischemia followed by
      2 days of reperfusion also prevented the neuronal destruction of the hippocampal
      CA1 region induced by 20-min ischemia.

PMID- 15248565
TI  - The impact of organic inhibitors of the hyperpolarization activated current (Ih)
      on the electroretinogram (ERG) of rodents.
AB  - We have compared the effect of two distinct Ih inhibitors on the temporal
      properties of the ERG response that, as previously shown, correlates well with
      the HCN activation in rods. The present results confirm the notion that
      cilobradine is more effective than zatebradine in inducing bradycardia.
      Importantly, the doses of cilobradine that reduce the heart rate to values
      comparable to, or lower than, those obtained with higher doses of zatebradine
      have little effect on the frequency response of the ERG. While more potent than
      zatebradine in its bradycardic action, cilobradine appears comparatively less
      effective on the visual response. A possible explanation is that the affinity of
      cilobradine for the HCN channels in the heart is higher than that for the HCN
      channels of retinal neurons.

PMID- 15248566
TI  - Antitumoural action of L-733,060 on neuroblastoma and glioma cell lines.
AB  - We have performed an in vitro study of the growth-inhibitory capacity of the
      potent and long-acting NK1 receptor antagonist L-733,060, at concentrations
      ranging from 2.5 microM to 20 microM, against the neuroblastoma cell line SKN
      BE(2) and 10 microM to 25 microM for glioma cell line GAMG. Coulter counter was
      used to determine viable cell numbers, followed by application of the tetrazolium
      compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4
      sulfophenyl)-2H-tetrazolium], inner salt colorimetric method to evaluate cell
      viability in this cytotoxicity assay. L-733,060 inhibited the growth of the two
      cell lines studied in a dose-dependent manner. The IC 50 values were 11.6 microM
      (30h) and 10.2 microM (72h) for SKN-BE(2); and 21.3 microM (48h) and 19.9 microM
      (96h) for GAMG. These findings indicate that the NK1 receptor antagonist L
      733,060 acts as a broad-spectrum antitumoural agent. This new action, reported
      here for the first time, suggests that the NK1 receptor antagonist L-733,060
      could be a promising therapeutic drug for the treatment of human neuroblastoma
      and human glioma.

PMID- 15248567
TI  - Impaired agonists recruitment during voluntary arm movements in patients affected
      by spasmodic torticollis.
AB  - We have investigated the electromyographic (EMG) and kinematic characteristics of
      horizontal arm extension movements in patients affected by idiopathic cervical
      dystonia (ICD) as well as in normal subjects. In spite of the lack of an overt
      dystonic involvement of the muscles acting at upper arm level, all these patients
      were considerably bradykinetic. Although the degree of bradykinesia observed was
      comparable to that previously reported for the body segment directly affected by
      this patholgy (21,15,8), the EMG analysis of the agonist muscles indicated a
      specific pathophysiological mechanism. In particular, the recruitment of the
      posterior deltoid (pD) in ICD patients was severely impaired within the initial
      phase (130 ms) of the movement. On the other hand, within the same time span, the
      activation of the mD, a muscle that plays a more important postural role than the
      pD, was not significantly different between patients and normal subjects. This
      reduced recruitment in the initial phase of the AG1 appears responsible of the
      slowness of voluntary movements.

PMID- 15248568
TI  - On two versions of a 3-pi algorithm for spiral CT.
AB  - A 3pi algorithm is obtained in which all the derivatives are confined to a
      detector array. Distance weighting of backprojection coefficients of the
      algorithm is studied. A numerical experiment indicates that avoiding
      differentiation along the source trajectory improves spatial resolution. Another
      numerical experiment shows that the terms depending on the non-standard distance
      weighting l/[x - y (s)] can no longer be ignored.

PMID- 15248569
TI  - An accelerated convergent ordered subsets algorithm for emission tomography.
AB  - We propose an algorithm, E-COSEM (enhanced complete-data ordered subsets
      expectation-maximization), for fast maximum likelihood (ML) reconstruction in
      emission tomography. E-COSEM is founded on an incremental EM approach. Unlike the
      familiar OSEM (ordered subsets EM) algorithm which is not convergent, we show
      that E-COSEM converges to the ML solution. Alternatives to the OSEM include
      RAMLA, and for the related maximum a posteriori (MAP) problem, the BSREM and OS
      SPS algorithms. These are fast and convergent, but require ajudicious choice of a
      user-specified relaxation schedule. E-COSEM itself uses a sequence of iteration
      dependent parameters (very roughly akin to relaxation parameters) to control a
      tradeoff between a greedy, fast but non-convergent update and a slower but
      convergent update. These parameters are computed automatically at each iteration
      and require no user specification. For the ML case, our simulations show that E
      COSEM is nearly as fast as RAMLA.

PMID- 15248570
TI  - A comparison of rotation- and blob-based system models for 3D SPECT with depth
      dependent detector response.
AB  - We compare two different implementations of a 3D SPECT system model for iterative
      reconstruction, both of which compensate for non-uniform photon attenuation and
      depth-dependent system response. One implementation performs fast rotation of
      images represented using a basis of rectangular voxels, whereas the other
      represents images using a basis of rotationally symmetric volume elements. In our
      simulations the blob-based approach was found to slightly outperform the rotation
      based one in terms of the bias-variance tradeoff in the reconstructed images.
      Their difference can be significant, however, in terms of computational load. The
      rotation-based method is faster for many typical SPECT reconstruction problems,
      but the blob-based one can be better-suited to cases where the reconstruction
      algorithm needs to process one volume element at a time.

PMID- 15248571
TI  - Microcalcification detection using cone-beam CT mammography with a flat-panel
      imager.
AB  - The purpose of this study was to investigate microcalcification detectability
      using CT mammography with a flat-panel imager. To achieve this, a computer
      simulation was developed to model an amorphous-silicon, CsI based flat-panel
      imager system using a linear cascaded model. The breast was modelled as a hemi
      ellipsoid shape with composition of 50% adipose and 50% glandular tissue.
      Microcalcifications were modelled as small spheres having a composition of
      calcium carbonate. The results show that with a mean glandular dose equivalent to
      that typically used in two-view screening mammography, CT mammography with a flat
      panel detector is capable of providing images where most microcalcifications are
      detectable. A receiver operating characteristic (ROC) study was conducted by five
      physicist observers viewing simulated CT mammography reconstructions. The results
      suggest that the microcalcification with its diameter equal to or greater than
      0.175 mm can be detected with an average area under the ROC curve (AUC) greater
      than 0.95 using 0.1 or 0.2 mm pixelized detectors. The results also indicate that
      the optimal pixel size of the detector is around 0.2 mm for microcalcification
      detection, based on the trade-off between detectability of microcalcifications
      and the time required for data acquisition and reconstruction.

PMID- 15248572
TI  - 3D tomographic reconstruction of coronary arteries using a precomputed 4D motion
      field.
AB  - In this paper, we present a new method to perform 3D tomographic reconstruction
      of coronary arteries from cone-beam rotational x-ray angiography acquisitions. We
      take advantage of the precomputation of the coronary artery motion, modelled as a
      parametric 4D motion field. Contrary to data gating or data triggering
      approaches, we homogeneously use all available frames, independently of the
      cardiac phase. In addition, we artificially subtract angiograms from their
      background structures. Our method significantly improves the reconstruction, by
      removing both motion and background artefacts. We have successfully tested it on
      the datasets from a synthetic phantom and 10 patients.

PMID- 15248573
TI  - Weighted FBP--a simple approximate 3D FBP algorithm for multislice spiral CT with
      good dose usage for arbitrary pitch.
AB  - A new 3D reconstruction scheme, weighted filtered backprojection (WFBP) for
      multirow spiral CT based on an extension of the two-dimensional SMPR algorithm is
      described and results are presented. In contrast to other 3D algorithms
      available, the algorithm makes use of all available data for all pitch values.
      The algorithm is a FBP algorithm: linear convolution of the parallel data along
      the row direction followed by a 3D backprojection. Data usage for arbitrary pitch
      values is maintained through a weighting scheme which takes into account
      redundant data. If proper row weighting is applied, the image quality is superior
      to the image quality of the SMPR algorithm.

PMID- 15248574
TI  - Redundant data and exact helical cone-beam reconstruction.
AB  - This paper is about helical cone-beam reconstruction and the use of redundant
      data in the framework of two reconstruction methods. The first method is the
      approximate wedge reconstruction formula introduced by Tuy at the 3D meeting in
      1999. The second method is a (exact) hybrid implementation of the exact filtered
      backprojection formula of Katsevich (2004 Adv. Appl. Math. at press) that
      combines filtering in the native cone-beam geometry with backprojection in the
      wedge geometry. The similarity of the two methods is explored and their image
      quality performance is compared for geometries with up to 112 detector rows.
      Furthermore, the concept of aperture weighting is introduced to allow the
      handling of variable amounts of redundant data. A reduction of motion artefacts
      using redundant data is demonstrated for geometries with 16, 32 and 112 detector
      rows using a pitch factor of 1.25. For scans with up to 100 rows, utilizing 50%
      of the redundant data provided excellent results without any introduction of cone
      beam artefacts. For larger cone angles, an alternative approach that utilizes all
      available redundant data, even at reduced pitch factors, is suggested.

PMID- 15248575
TI  - Cone-beam and fan-beam image reconstruction algorithms based on spherical and
      circular harmonics.
AB  - A cone-beam image reconstruction algorithm using spherical harmonic expansions is
      proposed. The reconstruction algorithm is in the form of a summation of inner
      products of two discrete arrays of spherical harmonic expansion coefficients at
      each cone-beam point of acquisition. This form is different from the common
      filtered backprojection algorithm and the direct Fourier reconstruction
      algorithm. There is no re-sampling of the data, and spherical harmonic expansions
      are used instead of Fourier expansions. As a special case, a new fan-beam image
      reconstruction algorithm is also derived in terms of a circular harmonic
      expansion. Computer simulation results for both cone-beam and fan-beam algorithms
      are presented for circular planar orbit acquisitions. The algorithms give
      accurate reconstructions; however, the implementation of the cone-beam
      reconstruction algorithm is computationally intensive. A relatively efficient
      algorithm is proposed for reconstructing the central slice of the image when a
      circular scanning orbit is used.

PMID- 15248576
TI  - CdZnTe strip detector SPECT imaging with a slit collimator.
AB  - In this paper, we propose a CdZnTe rotating and spinning gamma camera attached
      with a slit collimator. This imaging system acquires convergent planar integrals
      of a radioactive distribution. Two analytical image reconstruction algorithms are
      proposed. Preliminary phantom studies show that our small CdZnTe camera with a
      slit collimator outperforms a larger NaI(Tl) camera with a pinhole collimator in
      terms of spatial resolution in the reconstructed images. The main application of
      this system is small animal SPECT imaging.

PMID- 15248577
TI  - 3D RBI-EM reconstruction with spherically-symmetric basis function for SPECT
      rotating slat collimator.
AB  - A single photon emission computed tomography (SPECT) rotating slat collimator
      with strip detector acquires distance-weighted plane integral data, along with
      the attenuation factor and distance-dependent detector response. In order to
      image a 3D object, the slat collimator device has first to spin around its axis
      and then rotate around the object to produce 3D projection measurements. Compared
      to the slice-by-slice 2D reconstruction for the parallel-hole collimator and line
      integral data, a more complex 3D reconstruction is needed for the slat collimator
      and plane integral data. In this paper, we propose a 3D RBI-EM reconstruction
      algorithm with spherically-symmetric basis function, also called 'blobs', for the
      slat collimator. It has a closed and spherically symmetric analytical expression
      for the 3D Radon transform, which makes it easier to compute the plane integral
      than the voxel. It is completely localized in the spatial domain and nearly band
      limited in the frequency domain. Its size and shape can be controlled by several
      parameters to have desired reconstructed image quality. A mathematical lesion
      phantom study has demonstrated that the blob reconstruction can achieve better
      contrast-noise trade-offs than the voxel reconstruction without greatly degrading
      the image resolution. A real lesion phantom study further confirmed this and
      showed that a slat collimator with CZT detector has better image quality than the
      conventional parallel-hole collimator with NaI detector. The improvement might be
      due to both the slat collimation and the better energy resolution of the CZT
      detector.

PMID- 15248578
TI  - Impact of polychromatic x-ray sources on helical, cone-beam computed tomography
      and dual-energy methods.
AB  - Recently, there has been much work devoted to developing accurate and efficient
      algorithms for image reconstruction in helical, cone-beam computed tomography
      (CT). Little attention, however, has been directed to the effect of physical
      factors on helical, cone-beam CT image reconstruction. This work investigates the
      effect of polychromatic x-rays on image reconstruction in helical, cone-beam
      computed tomography. A pre-reconstruction dual-energy technique is developed to
      reduce beam-hardening artefacts and enhance contrast in soft tissue.

PMID- 15248579
TI  - Thermoacoustic tomography--consistency conditions and the partial scan problem.
AB  - Hybrid imaging techniques using either radiofrequency (RF) or near-infrared
      radiation (NIR) as excitation energy measure averages of tissue RF/NIR
      absorptivity over spheres centred at ultrasound (US) transducer locations on the
      bottom of a spherical bowl, where [z < 0]. Inversion formulae for the 'complete
      data' case where transducers measure all over the bowl weight data from the lower
      hemisphere more heavily for reconstructions points also satisfying (z < 0]. We
      derive consistency conditions for the data and use them to compute the unmeasured
      data corresponding to transducer locations on the top of the bowl. This process
      is clearly unstable, but somewhat tempered by the reconstruction's l/r weighting.

PMID- 15248580
TI  - Investigation of saddle trajectories for cardiac CT imaging in cone-beam
      geometry.
AB  - This paper investigates cone-beam tomography for a wide class of x-ray source
      trajectories called saddles. In particular, a mathematical analysis of the number
      of intersections between a saddle and an arbitrary plane is given. This analysis
      demonstrates that axially truncated cone-beam projections acquired along a saddle
      can be used for exact reconstruction at any point in a large volume. The
      reconstruction can be achieved either using a new algorithm presented herein or
      using a formula recently introduced by Katsevich (2003 Int. J. Math. Math. Sci.
      21 1305-21). The shape of the reconstructed volume and the properties of saddles
      make saddles attractive for cardiac imaging. Three examples of saddles are
      presented with a discussion of implementation on devices similar to modern C-arm
      systems and multislice CT scanners. Reconstruction with one of these saddles has
      been tested using computer-simulated data, with and without truncation. The
      imaged phantom for the truncated data is a FORBILD head phantom (representing the
      heart) that has been modified and embedded inside the FORBILD thorax phantom. The
      non-truncated data were generated by excluding the thorax. The reconstructed
      images demonstrate the accuracy of the mathematical results.

PMID- 15248581
TI  - A three-dimensional theoretical model incorporating spatial detection uncertainty
      in continuous detector PET.
AB  - In this paper, we will describe a theoretical model of the spatial uncertainty
      for a line of response, due to the imperfect localization of events on the
      detector heads of a positron emission tomography (PET) camera. The forward
      acquisition problem is modelled by a Gaussian distribution of the position of
      interaction on a detector head, centred at the measured position. The a
      posteriori probability that an event originates from a certain point in the field
      of view (FOV) is calculated by integrating all the possible lines of response
      (LORs) through this point, weighted with the Gaussian detection likelihood at the
      LOR's end points. We have calculated these a posteriori probabilities both for
      perpendicular and oblique coincidences. For the oblique coincidence case it was
      necessary to incorporate the effect of the crystal thickness in the calculations.
      We found in the perpendicular incidence case as well as in the oblique incidence
      case that the probability density function cannot be analytically expressed in a
      closed form, and it was thus calculated by means of numerical integration. A
      Gaussian was fit to the transversal profiles of this function for a given
      distance to the detectors. From these fits, we can conclude that the profiles can
      be accurately approximated by a Gaussian, both for perpendicular and oblique
      coincidences. The FWHM reaches a maximum at the detector heads, and decreases
      towards the centre of the FOV, as was expected. Afterwards we extended this two
      dimensional model to three dimensions, thus incorporating the spatial uncertainty
      in both transversal directions. This theoretical model was then evaluated and a
      very good agreement was found with theoretical calculations and with geometric
      Monte Carlo simulations. Possible improvements for the above-described
      incorporation of crystal thickness are discussed. Therefore a detailed Monte
      Carlo study has been performed in order to investigate the interaction
      probability of photons of different energies along their path in several detector
      materials dedicated to PET. Finally two approaches for the incorporation of this
      theoretical model in reconstruction algorithms are outlined.

PMID- 15248582
TI  - A new weighting scheme for cone-beam helical CT to reduce the image noise.
AB  - Reducing the patient dose while keeping the image noise at the same level is
      desired for x-ray CT examinations. In order to achieve the goal, we propose a new
      weighting scheme taking the validity of the data and redundant data samples into
      account. The method is evaluated with a new generalized version of the Feldkamp
      helical reconstruction algorithm. It allows us to enlarge the projection angular
      range used in reconstruction, and thus, to reduce the image noise by increasing
      the detector utilization rate to 100% without sacrificing the image quality or z
      resolution. This concept can be adapted to other exact or approximate algorithms
      as far as they use redundant data samples.

PMID- 15248583
TI  - Partial volume and aliasing artefacts in helical cone-beam CT.
AB  - A generalization of the quasi-exact algorithms of Kudo et al (2000 IEEE Trans.
      Med. Imaging 19 902-21) is developed that allows for data acquisition in a
      'practical' frame for clinical diagnostic helical, cone-beam computed tomography
      (CT). The algorithm is investigated using data that model nonlinear partial
      volume averaging. This investigation leads to an understanding of aliasing
      artefacts in helical, cone-beam CT image reconstruction. An ad hoc scheme is
      proposed to mitigate artefacts due to the nonlinear partial volume and aliasing
      artefacts.

PMID- 15248584
TI  - Sampling conditions of 3D parallel and fan-beam x-ray CT with application to
      helical tomography.
AB  - We give the sampling conditions of the 3D fan-beam x-ray transform (3DFBXRT). The
      motivation of this work lies in the fact that helical tomography with a single
      detector line is simply a sampling of this transform under the helical
      constraint. We give a precise description of the geometry of the essential
      support of the 3DFBXRT Fourier transform and show how to derive efficient
      sampling schemes. We then give efficient sampling schemes in parallel helical
      tomography. We present numerical experiments showing that efficient sampling on
      hexagonal interlaced schemes yields better reconstructions than the standard
      schemes in both parallel helical tomography (using QDO) and 3DFBXRT. We discuss
      the practical drawbacks and advantages of these efficient schemes and the
      possible extension to fan-beam helical CT.

PMID- 15248585
TI  - Approximate analytic reconstruction in x-ray fluorescence computed tomography.
AB  - X-ray fluorescence computed tomography (XFCT) is an emerging imaging modality
      that allows for the reconstruction of the distribution of nonradioactive elements
      within a sample from measurements of fluorescence x-rays produced by irradiation
      of the sample with monochromatic synchrotron radiation. XFCT is not a
      transmission tomography modality, but rather a stimulated emission tomography
      modality and thus correction for attenuation of the incident and fluorescence
      photons is essential if accurate images are to be obtained. In this work, we
      develop and characterize an approximate analytic approach to image reconstruction
      with attenuation correction in XFCT that is applicable when the incident beam
      attenuation is uniform and when a factor involving fluorescence attenuation and
      solid angle effects satisfies a certain approximation. When these conditions
      hold, we demonstrate that the XFCT imaging equation reduces to the exponential
      Radon transform, which can be readily inverted. The necessary approximation
      worsens as the total fluorescence attenuation in the sample grows, but the
      approach is found to be relatively robust as the approximation breaks down. In a
      long-axis, small solid angle geometry the proposed approach performs comparably
      to a previously proposed, more computationally expensive approximate method
      across a range of attenuation levels. In a short-axis, large solid angle
      geometry, the proposed approach is found to outperform this previous method.

PMID- 15248586
TI  - An exact Fourier rebinning algorithm for 3D PET imaging using panel detectors.
AB  - Abstract We present an exact Fourier-based algorithm for rebinning 3D data
      generated by a stationary dual-panel PET system to obtain direct slices for
      subsequent slice-by-slice reconstruction. The algorithm is computationally
      efficient and can greatly reduce the problem dimensionality and computation
      complexity of the reconstruction task. By conducting computer simulation studies
      in which the effects of scatter, randoms, detector response functions and
      attenuation correction are not considered, we demonstrate that direct slices
      generated by the proposed algorithm are quantitatively accurate and exhibit
      substantially better noise characteristics than the original direct slices.
      However, image artefacts, occurring at axial intensity discontinuities and in
      regions close to the axial axis, can be observed. With preliminary supporting
      evidence, we stipulate that these artefacts are due to errors in discrete
      implementations of partial derivatives of the 3D data. Although general
      weightings can be used in the proposed rebinning algorithm, in this work we only
      study the use of uniform weightings and the resulting direct slices exhibit non
      uniform noise distributions, with the central slices being less noisy. In future
      studies, by using general weightings to reduce contributions of the data that are
      acquired at large oblique angles, we expect that more uniform noise distributions
      can be achieved, and axial blurring due to parallax errors can be reduced, at the
      cost of overall image variance.

PMID- 15248587
TI  - Application of discrete data consistency conditions for selecting regularization
      parameters in PET attenuation map reconstruction.
AB  - Simultaneous emission and transmission measurement is appealing in PET due to the
      matching of geometrical conditions between emission and transmission and reduced
      acquisition time for the study. A potential problem remains: when transmission
      statistics are low, attenuation correction could be very noisy. Although noise in
      the attenuation map can be controlled through regularization during statistical
      reconstruction, the selection of regularization parameters is usually empirical.
      In this paper, we investigate the use of discrete data consistency conditions
      (DDCC) to optimally select one or two regularization parameters. The advantages
      of the method are that the reconstructed attenuation map is consistent with the
      emission data and that it accounts for particularity in the emission
      reconstruction algorithm and acquisition geometry. The methodology is validated
      using a computer-generated whole-body phantom for both emission and transmission,
      neglecting random events and scattered radiation. MAP-TR was used for attenuation
      map reconstruction, while 3D OS-EM is used for estimating the emission image. The
      estimation of regularization parameters depends on the resolution of the emission
      image controlled by the number of iterations in OS-EM. The computer simulation
      shows that, on one hand, DDCC regularized attenuation map reduces propagation of
      the transmission scan noise to the emission image, while on the other hand DDCC
      prevents excessive attenuation map smoothing that could result in resolution
      mismatch artefacts between emission and transmission.

PMID- 15248588
TI  - Positron emission mammography with tomographic acquisition using dual planar
      detectors: initial evaluations.
AB  - Positron emission mammography (PEM) with tomographic acquisition using dual
      planar detectors rotating about the breast can obtain complete angular sampling
      and has the potential to improve activity estimation compared with PEM using
      stationary detectors. PEM tomography (PEMT) was compared with stationary PEM for
      point source and compressed breast phantom studies performed with a compact dual
      detector system. The acquisition geometries were appropriate for the target
      application of PEM guidance of stereotactic core biopsy. Images were
      reconstructed with a three-dimensional iterative maximum likelihood expectation
      maximization algorithm. PEMT eliminated blurring normal to the detectors seen
      with stationary PEM. Depth of interaction effects distorted the shape of the
      point spread functions for PEMT as the angular range from normal incidence of
      lines of response used in image reconstruction increased. Streak artefacts in
      PEMT for large detector rotation increments led to the development of an
      expression for the maximum rotation increment that maintains complete angular
      sampling. Studies with a compressed breast phantom were used to investigate
      contrast and signal-to-noise ratio (SNR) trade-offs for different sized spherical
      tumour models. PEMT and PEM both had advantages depending on lesion size and
      detector separation. The most appropriate acquisition method for specific
      detection or quantitation tasks requires additional investigation.

PMID- 15248589
TI  - Spiral scan long object reconstruction through PI line reconstruction.
AB  - The response of a point object in a cone beam (CB) spiral scan is analysed. Based
      on the result, a reconstruction algorithm for long object imaging in spiral scan
      cone beam CT is developed. A region-of-interest (ROI) of the long object is
      scanned with a detector smaller than the ROI, and a portion of it can be
      reconstructed without contamination from overlaying materials. The top and bottom
      surfaces of the ROI are defined by two sets of PI lines near the two ends of the
      spiral path. With this novel definition of the top and bottom ROI surfaces and
      through the use of projective geometry, it is straightforward to partition the
      cone beam image into regions corresponding to projections of the ROI, the
      overlaying objects or both. This also simplifies computation at source positions
      near the spiral ends, and makes it possible to reduce radiation exposure near the
      spiral ends substantially through simple hardware collimation. Simulation results
      to validate the algorithm are presented.

PMID- 15248590
TI  - Distance-driven projection and backprojection in three dimensions.
AB  - Projection and backprojection are operations that arise frequently in tomographic
      imaging. Recently, we proposed a new method for projection and backprojection,
      which we call distance-driven, and that offers low arithmetic cost and a highly
      sequential memory access pattern. Furthermore, distance-driven projection and
      backprojection avoid several artefact-inducing approximations characteristic of
      some other methods. We have previously demonstrated the application of this
      method to parallel and fan beam geometries. In this paper, we extend the distance
      driven framework to three dimensions and demonstrate its application to cone beam
      reconstruction. We also present experimental results to demonstrate the
      computational performance, the artefact characteristics and the noise-resolution
      characteristics of the distance-driven method in three dimensions.

PMID- 15248591
TI  - The cognitive, emotional, and social impacts of the September 11 attacks: group
      differences in memory for the reception context and the determinants of flashbulb
      memory.
AB  - The authors examined group differences in memories for hearing the news of and
      reactions to the September 11 attacks in 2001. They measured memory for reception
      context (immediate memory for the circumstances in which people first heard the
      news) and 11 predictors of the consistency of memory for reception context over
      time (flashbulb memory). Shortly after 9/11, a questionnaire was distributed to
      3,665 participants in 9 countries. U.S. vs. non-U.S. respondents showed large
      differences in self-rated importance of the news and in memory for event-related
      facts. The groups showed moderate differences in background knowledge and
      emotional-feeling states. Within non-U.S. groups, there were large differences
      for emotional-feeling states and moderate differences for personal rehearsal,
      background knowledge, and attitudes toward the United States. The authors discuss
      the implications of those findings for the study of group differences in memory
      and for the formation of flashbulb memories.

PMID- 15248592
TI  - Priming guesses on a forced-recall test.
AB  - The forced-recall paradigm requires participants to fill all spaces on the memory
      test even if they cannot remember all the list words. In the present study, the
      authors used that paradigm to examine the influence of implicit memory on
      guessing--when participants fill remaining spaces after they cannot remember list
      items. They measured explicit memory as the percentage of targets that
      participants designated as remembered from the list and implicit memory as the
      percentage of targets they wrote but did not designate as remembered (beyond
      chance level). The authors examined implicit memory on guessing with forced
      recall (Experiment 1), forced cued recall with younger and older adults
      (Experiment 2), and forced free and cued recall under a depth-of-processing
      manipulation (Experiment 3). They conclude that implicit memory influences
      guesses of targets in the forced-recall paradigm.

PMID- 15248593
TI  - Error detection in text: do feedback and familiarity help?
AB  - In the present study, the authors examined the extent to which familiarity and
      feedback (auditory and/or articulatory) might be beneficial to proofreading.
      Participants proofread unfamiliar and familiar (repeated) passages while (a)
      concurrently reading either aloud or silently, (b) concurrently listening to the
      passages being read to them, or (c) reading without either auditory or
      articulatory feedback. Errors were one-letter changes that transformed function
      words into contextually inappropriate words. Familiarity improved reading times
      largely irrespective of feedback, and it enhanced error detection only when
      auditory feedback was available to participants. Proofreaders' enhanced error
      detection in familiar text reflected a change in their sensitivity to errors
      rather than any change in the placement of the response criterion for reporting
      errors. These findings suggest that familiarity can produce two kinds of
      functional fluency, one involving speed of processing, which is largely
      independent of feedback, and the other concerned with accuracy of processing,
      which relies on feedback.

PMID- 15248594
TI  - N400 and P600 or the role of the ERP correlates in sentence comprehension: some
      applications to the Italian language.
AB  - In the present study, event-related brain potentials (ERPs) were applied to the
      study of language comprehension in the Italian language. The ERPs were recorded
      from 10 electrodes while the participants read (Experiment 1) or listened
      (Experiment 2) to sentences containing semantic or syntactic anomalies. Final
      words that were inconsistent with the sentence context elicited a negative wave
      at about 400 ms poststimulus that was more concentrated in the posterior sites of
      the scalp, whereas final words that were incongruous with the grammatical
      structure (subject-verb nonagreement) elicited a positive wave at about 600 ms
      poststimulus that was homogeneously distributed on the scalp. The authors found
      no differences based on the perceptual modality of the stimulus (visual or
      auditory), nor did they find different ERP correlates as a function of task
      relevance (explicit-implicit task induction). The available evidence indicated
      that the ERP response to semantic anomalies was at least partially distinct from
      the ERP response to syntactic anomalies, and that a syntactic parser is a
      plausible process included in sentence comprehension. The two semantic and
      syntactic effects appear as automatic processes of the decoding of the anomalies
      and also modality-independent processes. Cross-linguistic applications are
      considered in the general discussion.

PMID- 15248595
TI  - Sexual experiences associated with participation in drinking games.
AB  - The results of previous research suggest that participation in drinking games may
      be associated with sexual aggression, but the specific sexual behaviors involved
      have not been identified. In the present study, the authors attempted to identify
      specific sexual experiences associated with drinking games. Both men and women
      reported being taken advantage of sexually during or after play, including
      someone having sex with them when they were too drunk to give consent. Few women
      admitted to being perpetrators, but many men reported multiple instances of
      perpetration. Greater alcohol consumption predicted more sexual experiences in
      women. In men, sexual motives for playing drinking games were the best predictor
      of sexual behavior. Alcohol and sexual-assault prevention programs may need to
      consider the role of drinking games in sexual victimization.

PMID- 15248596
TI  - Generation of a total of 6483 expressed sequence tags from 60 day-old bovine
      whole fetus and fetal placenta.
AB  - Expressed sequence tags (ESTs) generated based on characterization of clones
      isolated randomly from cDNA libraries are used to study gene expression profiles
      in specific tissues and to provide useful information for characterizing tissue
      physiology. In this study, two directionally cloned cDNA libraries were
      constructed from 60 day-old bovine whole fetus and fetal placenta. We have
      characterized 5357 and 1126 clones, and then identified 3464 and 795 unique
      sequences for the fetus and placenta cDNA libraries: 1851 and 504 showed homology
      to already identified genes, and 1613 and 291 showed no significant matches to
      any of the sequences in DNA databases, respectively. Further, we found 94 unique
      sequences overlapping in both the fetus and the placenta, leading to a catalog of
      4165 genes expressed in 60 day-old fetus and placenta. The catalog is used to
      examine expression profile of genes in 60 day-old bovine fetus and placenta.

PMID- 15248597
TI  - Increased milk yield in transgenic mice expressing insulin-like growth factor 1.
AB  - Insulin-like growth factor 1 (IGF-1) mediates many of the actions of growth
      hormone. Overexpression of IGF-1 was reported to have endocrine and
      paracrine/autocrine effects on somatic growth in transgenic mice. To study the
      paracrine/autocrine effects of IGF-1 in mammary gland, transgenic mice were
      produced by pronuclear microinjection of a construct containing a bovine alpha
      lactalbumin (alpha-LA) promoter linked to an ovine IGF-1 cNDA. This alpha-LA
      promoter has previously been shown to direct expression of a human factor VIII
      gene specifically to the mammary gland of transgenic mice. Three transgenic mouse
      lines were established as a result of microinjection of 398 embryos. Transgene
      expression was found in mammary gland at day 1 of lactation from these three
      lines. Progeny test were carried out by mating two transgenic males/one
      transgenic female to two nontransgenic females/one nontransgenic male. Mice from
      one line (line 1225) were all nonexpressors and the other (line 1372) failed to
      produce offspring. Milk yield was analyzed in the line 1137 that produced 10
      mice, of which three were transgenic females and three nontransgenic females. All
      of the three transgenic females showed integration of the transgene and expressed
      transgene IGF-1 mRNA in the mammary gland. Milk yields from days 5, 10, and 15 of
      lactation were significant greater in transgenic expressors than in their
      nontransgenic littermates. Specifically, there is 17.9% increase in total milk
      yield from these three days for transgenics compared with nontransgenics. These
      results demonstrate that local overexpression of IGF-1 in transgenic mice is
      capable to stimulating milk yield during the first lactation.

PMID- 15248598
TI  - Variable expression of human lactoferrin gene in mice milk driven by its 90 KB
      upstream flanking sequences.
AB  - One major drawback in research of animal mammary gland bioreactors is the low
      production rate of high-expressing transgenic animals due to position effects. To
      obtain high and stable expression of foreign gene, yeast and bacterial artificial
      chromosome have been used as transgene vector in recent research. Human
      lactoferrin is a bioactive, versatile protein, and has large potential in
      nutritional and therapeutic applications. Therefore, production of recombinant
      lactoferrin using animal bioreactors was studied widely to satisfy its large
      requirement. We reported here a transgenic mice model with high-level expression
      of recombinant human lactoferrin in mammary gland. Transgene construct used here
      was a human bacterial artificial chromosome containing intact lactoferrin
      encoding transcript unit, approximately 90 kb 5'-flanking sequences and 27.2 kb
      3'-flanking sequences. We obtained totally 10 transgenic mice whereas two of them
      lacked of part of upstream sequences of the gene. Milk of eight transgenic mice
      line was detected by Western blot and radioimmunoassay and seven lines expressed
      recombinant human lactoferrin at high but variable level (0.29, 0.53, 0.90, 1.23,
      2.76, 3.58, and 8.02 mg/mL, respectively). The variability of expression
      indicates that even the 90 kb 5' flanking sequence of the transgene can't
      overcome position effects completely. Moreover, we also determined sequences of
      9.3 kb regulatory region and 10.6 kb encoding region of the gene and thus
      supplemented all unknown sequences. Our results suggested that transgene vector
      used here has potential to be used in large farm animals for production of
      recombinant human lactoferrin in industrial scale.

PMID- 15248599
TI  - Growth and tissue accretion rates of swine expressing an insulin-like growth
      factor I transgene.
AB  - The goal of this research was to determine whether directing expression of an
      insulin-like growth factor I (IGF-I) transgene specifically to striated muscle
      would alter the growth characteristics in swine. Transgenic pigs were produced
      with a fusion gene composed of avian skeletal alpha-actin regulatory sequences
      and a cDNA encoding human IGF-I. Six founder transgenic pigs were mated to
      nontransgenic pigs to produce 11 litters of G1 transgenic and sibling control
      progeny. Birth weight, weaning weight, and proportion of pig survival did not
      differ between transgenic and control pigs. The ADG of pigs as they grew
      incrementally from 20 to 60 kg, 60 to 90 kg, and 90 to 120 kg, respectively, did
      not significantly differ between transgenic and control pigs. Efficiency of feed
      utilization (gain:feed) was also similar for transgenic and control pigs. Plasma
      IGF-I and porcine growth hormone (pGH) concentrations were determined at 60, 90,
      and 120 kg body weight. Plasma IGF-I concentrations were 19% higher in transgenic
      gilts than control gilts and 11.1% higher in transgenic boars than control boars
      (P=0.0005). Plasma IGF-I concentrations for boars were also higher than for gilts
      (P=0.0001). At 60, 90, and 120 kg body weight each pig was scanned by dual energy
      X-ray absorptiometry (DXA) to derive comparative estimates of carcass fat, lean,
      bone content of the live animal. Control pigs had more fat and less lean tissue
      than transgenic pigs at each of the scanning periods and the difference became
      more pronounced as the pigs grew heavier (P<0.005 at each weight). Transgenic
      pigs also had a slightly lower percentage of bone than control pigs (P<0.05 at
      each weight). While daily rates of lean tissue accretion did not differ for
      transgenic and control pigs, daily rates of fat accretion were lower in
      transgenic pigs than in control pigs (P<0.05). Based on these results we conclude
      that expression of IGF-I in the skeletal muscles gradually altered body
      composition as pigs became older but did not have a major affect on growth
      performance.

PMID- 15248600
TI  - Cloning of bovine pyruvate carboxylase and 5' untranslated region variants.
AB  - Bovine pyruvate carboxylase (PC; EC 6.4.1.1) cDNA was cloned by reverse
      transcription (RT) PCR. The coding region plus 3' untranslated region (UTR) of PC
      mRNA is 3926 bases and encodes 1178 amino acid PC precursor protein. A 5' rapid
      amplification of cDNA ends protocol was used to clone the 5' end of the mRNA. Six
      5'UTR variants ranging from 68 to 363 bp were cloned. Bovine PC 5'UTR (bPC5')
      variants contain 68 (bPC5'A), 263 (bPC5'B), 363 (bPC5'C), 89 (bPC5'D), 275
      (bPC5'E), and 178 bp (bPC5'F). All variants contain a common coding sequence. An
      RNase protection assay and RT-PCR analysis confirms the presence of the 5'UTR
      variants. The abundance of PC mRNA, determined by Northern blot analysis,
      indicates that PC is more abundant in gluconeogenic and lipogenic tissues where
      all PC variants are expressed compared with tissues that do not possess the full
      spectrum of PC transcripts. The data suggest that bPC5'A, bPC5'B, and bPC5'F are
      more abundant in bovine liver than the other variants.

PMID- 15248601
TI  - Study on the polymorphism of bovine lactoferrin gene and its relationship with
      mastitis.
AB  - Mastitis is a major cause of economic loss to the dairy industry. Lactoferrin
      (Lf) is known to contribute to resistance against bacterial infections. Hence, we
      decided to characterize the relevance between mastitis resistance and the
      variants of Lf gene. By using PCR-SSCP, five fragments within 5' region and all
      exons of bovine lactoferrin gene were amplified and identified the nucleotide
      diversity. For the five segments within the 5'-region: Lf5'-1, Lf5'-2, Lf5'-3,
      Lf5'-4, and Lf5'-5 from upstream to downstream, we found that three had base
      variation. Totally, mutations were observed in Lf5'-1, Lf5'-3, and Lf5'-5, exons
      4, 8, 9, 11, 15, and intron 4. We analyzed the effects of all mutated loci on
      milk production traits with least squares method.

PMID- 15248602
TI  - The interferon-alpha genes from three chicken lines and its effects on H9N2
      influenza viruses.
AB  - The interferon-alpha genes from three chicken lines were cloned by a direct PCR
      technique, and the effects of recombinant protein expressed in a prokaryotic
      system on highly pathogenic H9N2 influenza viruses were investigated. The cloned
      ChIFN-alpha gene encoded a protein of 193 amino acids with a signal sequence of
      31 amino acids and mature peptides of 162 amino acids. Comparison of ChIFN-alpha
      sequences, detected six amino acids substitutions at positions 50, 58, 65, 81,
      181, and 183. Homology analysis indicated that ChIFN-alpha genes could be
      subdivided into two lineages, SH-ChIFN-alpha and WJ-ChIFN-alpha. In addition,
      both SH-ChIFN-alpha and WJ-ChIFN-alpha were expressed with the N-terminal 6
      consecutive histidine residues in a high-level prokaryotic expression system.
      Recombinant chicken interferon-alpha (rChIFN-alpha) protein has anti-VSV activity
      of more than 1 x 10(8) U/mg. Moreover, High concentration (10,000U) of rSH-ChIFN
      alpha resulted in over 40% inhibition of the H9N2 virus infection in chicken
      embryos (Ovo), and 100% inhibition from one day-old to five day-old chickens
      (Vivo). The results suggested that rChIFN-alpha is a potential agent against many
      Chicken viral strains.

PMID- 15248603
TI  - Characterization of porcine leptin receptor polymorphisms and their association
      with reproduction and production traits.
AB  - Fatness in pigs is of prime economic importance due to market incentives for
      production of lean pork and elevated fatness increasing the feed costs. Leptin
      (LEP) action, mediated through its specific receptors (LEPR), was reported to be
      involved in the regulation of fatness via feed intake, energy expenditure, and
      whole-body energy balance in pigs. In this study, we have designed 17 primer sets
      based on the human and mouse LEPR sequences and successfully amplified coding
      regions of 15 porcine LEPR exon fragments by polymerase chain reactions (PCR).
      Four single nucleotide polymorphisms (SNP) of Intron 2, Exons 2, 6, and 18 were
      found in Landrace, Yorkshire, and Duroc by mutagenetically separated-PCR (MS-PCR)
      and PCR-restriction fragment length polymorphisms (PCR-RFLP). Chi-square
      statistics was used to calculate homogeneity of genotypic frequencies of 4 gene
      polymorphisms for three breeds of animals. Effects of Intron 2, Exon 2, and Exon
      18 polymorphisms on the reproduction trait such as litter sizes of sows were
      evident (p < 0.05) in Duroc and Yorkshire. There was no (p > 0.05) significant
      influence on the production trait of average daily gain due to four candidate
      gene polymorphisms in three porcine breeds. However, effects of Exon 6 and 18
      polymorphisms on the production trait of backfat thickness were significant (p <
      0.05) in Landrace and Yorkshire, respectively. Effects of Exon 18 polymorphisms
      on feed efficiency were also evident (p < 0.05) in Duroc.

PMID- 15248604
TI  - 1-Substituted beta-carboline-3-carboxylates with high affinities to the
      benzodiazepine recognition site.
AB  - Naturally occurring derivatives of beta-carboline-3-carboxylic acid bearing
      acetyl or vinyl groups at C-1 were prepared by Pd-catalyzed cross-coupling
      reactions of methyl 1-chloro-beta-carboline-3-carboxylate with appropriate
      organostannanes. Esters with chloro or acetyl groups at C-1 showed high affinity
      for the brain benzodiazepine recognition site. Thus, in contrast to 1-alkyl and 1
      aryl analogs, these beta-carboline-3-carboxylates with electron-withdrawing
      substituents at C-1 show high affinities.

PMID- 15248605
TI  - A new approach towards ikimine A analogues.
AB  - An analogon of the alkylpyridine alkaloid ikimine A (1) was prepared in six steps
      starting from undec-10-ynoic acid. A key step in this synthesis was a Sonogashira
      coupling of the alkyne and 3-iodopyridine, followed by hydrogenation of the
      alkyne, reduction of the ester to the primary alcohol and oxidation to the
      corresponding aldehyde. This aldehyde was converted to the ikimine A analogon
      with O-methyl hydroxylamine hydrochloride. This product and the intermediate
      alkylpyridines were tested in the agar diffusion assay for antibacterial and
      antifungal activities.

PMID- 15248606
TI  - Two new polyporusterones from Polyorus umbellatus.
AB  - Two new polyporusterones named as porusterone I and polyprosterone II were
      isolated from polyourus umbellatus. Their structures have been established on the
      basis of spectroscopic analysis.

PMID- 15248607
TI  - Alkylated isocoumarins from Pituranthos scoparius.
AB  - Two isocoumarins have been isolated from the ethyl acetate extract of the root of
      Pituranthos scoparius: 3-n-propyl-5-methoxy-6-hydroxy-isocoumarin and 3-n-propyl
      5,7-dimethoxy-6-hydroxy-isocoumarin. Their structures were assigned by spectral
      analysis.

PMID- 15248608
TI  - Two new limonoids from Munronia henryi.
AB  - Two new limonoids, munronolide (1) and munronolide 21-O-beta-D-glucopyranoside
      (2), were isolated from the whole plant of Munronia henryi (Meliaceae). Their
      structures have been elucidated on the basis of spectroscopic and chemical
      methods. The D-glucose moiety attached to C-21 position of limonoid is firstly
      reported.

PMID- 15248609
TI  - Three new glutarimide alkaloids from Croton cuneatus.
AB  - Analysis of the dichloromethane extract of the aerial parts of Croton cuneatus
      led to the isolation of the new glutarimide alkaloids: julocrotol (1),
      isojulocrotol (2), and julocrotone (3) along with the known compounds
      julocrotonine (4), lichexanthone (5) and selin-11-en-4alpha-ol (6). The
      structures of the new compounds were established by spectral methods. The in
      vitro cytotoxic activity of Compounds 1-6 was evaluated against six human tumor
      cells lines.

PMID- 15248610
TI  - 2,4,5-Tribromo-1H-imidazole in the egg masses of three muricid molluscs.
AB  - From analysis by gas chromatography/mass spectrometry (GC/MS), the presence of
      either 2,4,5-tribromo-1H-imidazole (1) or 3,4,5-tribromo-1H-pyrazole (2) was
      tentatively identified in lipophilic extracts from the egg masses of three
      muricid molluscs. Synthesis of these compounds, followed by comparison of the GC
      retention times and fragmentation patterns from electron impact MS, with those of
      the natural products, indicated that it was 2,4,5-tribromo-1H-imidazole rather
      than the pyrazole. This imidazole is likely to be responsible for some of the
      antimicrobial activity observed in the egg extracts. This is the first report of
      this compound from a natural source.

PMID- 15248611
TI  - Minor gamma-lactones from Trichilia catigua (Meliaceae) and its precursors by GC
      MS.
AB  - NMR and GC-MS analysis of fractions of the CHCl3 extract of Trichilia catigua
      bark led to the identification of a mixture of three omega-phenyl alkanes, three
      omega-phenyl alkanoic acids, five omega-phenyl-gamma-lactones, two alkyl-gamma
      lactones, one alkenyl-gamma-lactone and a mixture of fatty acids ranging from C
      14 to C-26. Beta-sitosterol, stigmasterol and campesterol as free alcohols were
      also identified.

PMID- 15248612
TI  - Chemical constituents from Pseudolarix kaempferi.
AB  - A novel degraded triterpenoid isopseudolaritone A (1) and one new
      oligosaccharide, 1-O-isopropyl-6-O-[2-O-methyl-alpha-L-rhamnopyranosyl(1 --> 6)]
      beta-D-glucopyranose (2), two new artefacts, 9-O-formacyl cedrusin (5) and 9,9'-O
      diformacyl cedrusin (6), as well as 12 known phenolic Compounds (3-4, 7 16), were
      isolated from the root bark of Pseudolarix kaempferi. Their structures were
      elucidated mainly by spectroscopic methods.

PMID- 15248613
TI  - Paludolactone: a new eudesmanolide lactone from Wedelia paludosa DC. (Acmela
      brasiliensis).
AB  - Phytochemical investigation of the whole plant of Wedelia paludosa (Acmela
      brasiliensis) furnished a new eudesmanolide lactone, named paludolactone (2), in
      addition to the known eudesmanolide (1), stigmasterol, kaurenoic and oleanolic
      acids. 1H- and 13C-NMR, and MS spectroscopic and elemental analyses were used for
      the structural elucidation of these compounds.

PMID- 15248614
TI  - Serratane-type triterpenoids from Huperzia serrata.
AB  - Sixteen serratane-type triterpenoids including three new compounds, 14beta,15beta
      epoxyserratan-3beta,21beta,29-triol (1), serrat-14-en-3beta,21beta,29-triol (2)
      and serrat-14-en-3alpha,21beta,24,29-tetraol (3), were isolated from the whole
      plant of Huperzia serrata (Thunb) Trev. The structures of these new compounds (1
      3) were elucidated on the basis of spectral analysis.

PMID- 15248615
TI  - Spirodepressolide: an unusual bis-norsesquiterpene lactone from Achillea depressa
      Janka.
AB  - A new bis-norsesquiterpene lactone, spirodepressolide (1), has been isolated from
      the aerial parts of Achillea depressa Janka and its structure determined by
      spectroscopic methods to have a new 4-methyl-7-methylethyl
      spirobicyclo[4,4]nonane skeleton.

PMID- 15248616
TI  - Two new isoflavanoids from the rhizomes of Iris soforana.
AB  - Two new isoflavones 1 and 2 along with eleven known compounds 3-13, have been
      isolated for the first time from the rhizomes of Iris soforana. The structures of
      these compounds were determined on the basis of spectroscopic methods and found
      to be 5,3'-dihydroxy-4'-methoxy-6,7-methylenedioxyisoflavone (1) (Soforanarin A),
      and 5,7,5'-trimethoxy-6,3',4'-trihydroxyisoflavone (2) (Soforanarin B).

PMID- 15248617
TI  - Piptigrine, a new insecticidal amide from Piper nigrum Linn.
AB  - A new insecticidal amide piptigrine (1) possessing highly extended conjugation
      was isolated from the dried ground seeds of Piper nigrum Linn. along with the
      known amides piperine and wisanine (hitherto unreported from this plant). The
      structure of 1 has been elucidated as 1-[9-(3',4'-methylenedioxyphenyl)-4E,6E,8E
      nonatrienoyl]piperidine through extensive 1D- and 2D-NMR (COSY-45, NOESY, J
      resolved, HMQC, HMBC and NOESY studies. The known compounds have been identified
      through comparison of their spectral data with those reported in literature. 1
      exhibited toxicity of 15.0 ppm against fourth instar larvae of Aedes aegypti
      Liston.

PMID- 15248618
TI  - Isolation of cytotoxic chondropsins, macrolide lactams from the New-Caledonian
      marine sponge Psammoclemma sp. and electrospray ion trap multiple stage MS study
      of these macrolides.
AB  - Psammoclemma sp. (Phoriospongiidae) was selected for study through biological
      screening carried out in New Caledonia. The crude extract of Psammoclemma sp. was
      highly active on KB cells and its fractionation led to the isolation of two
      macrolides chondropsin A 1 and 73-deoxychondropsin A 2. The complex structures
      were elucidated by a combination of spectroscopic methods (NMR, ESI-MS/MS). These
      known compounds were evaluated for their cytotoxic activity towards several tumor
      cell lines and exhibited an IC50 of approximately 10(-10) M. Flow-cytometric
      analysis revealed that chondropsin A 1 and 73-deoxychondropsin A 2 blocked the
      entry of HL 60 and KB cells into G2/M phase, leading to cell death by apoptosis.

PMID- 15248619
TI  - Anaesthesia acronyms and abbreviations.

PMID- 15248620
TI  - Monitoring depth of anaesthesia: is it worth the effort?
AB  - In this review paper, the authors critically analyse the use of a number of depth
      of anaesthesia monitors in light of the most recent literature and their own
      clinical experience. There appears to be increasing evidence that anaesthesia
      depth monitors reduce the incidence of unexpected intraoperative awareness and
      also that they improve the quality of anaesthesia. Proper use of these monitors
      necessitates background knowledge about the physiology of the loss of
      consciousness, the type of variable recorded and processed by the monitoring
      devices, the factors that might interfere with recording and the limits of use.
      The information provided by anaesthesia depth monitors is detailed and
      relationships with clinical practice are established to provide the reader with
      key features for optimal use of those monitors and correct interpretation of
      data. Practitioners and patient's knowledge and expectations regarding this
      matter, as well as the cost-benefit relationship are also discussed.

PMID- 15248621
TI  - Observations on intraoperative monitoring of visual pathways using steady-state
      visual evoked potentials.
AB  - BACKGROUND AND OBJECTIVE: Former studies revealed conflicting information on the
      usefulness of intraoperative monitoring of visual evoked potentials. This study
      was designed to evaluate the characteristics of visual evoked potential recording
      in surgically anaesthetized patients using the modality of steady-state visual
      evoked potentials. METHODS: In 30 cases with non-cranial surgery steady-state
      visual evoked potentials were recorded in the awake and surgically anaesthetized
      patient using total intravenous anaesthesia. For stimulation, goggles with red
      light-emitting diodes at a frequency of 8.5 Hz were used. A two-channel recording
      with silver cup electrodes at Oz to Fz and Oz to earlobe was used. All traces
      were analysed for the presence of the characteristically sinusoidal waveform and
      amplitudes and latencies of the main peaks were measured. RESULTS: Recordings
      during surgery demonstrated a minor latency prolongation of 16% and a more
      pronounced amplitude attenuation of 67% compared to the recordings in the awake
      patients. These differences were statistically significant (paired t-test, P <
      0.001). In surgically anaesthetized patients steady-state visual evoked
      potentials showed a relatively high intra- and interindividual variability. In
      four of 30 patients completely stable recordings were obtained, whereas in 14
      patients identifiable waves were recordable in only less than 50% of the
      intraoperative traces. Of the total 1360 traces recorded intraoperatively clearly
      identifiable steady-state visual evoked potentials patterns were present in 56%
      of the traces. There was no correlation between the magnitude of the evoked
      potential amplitude and its stability in intraoperative recordings. CONCLUSIONS:
      We conclude from this study, that steady-state visual evoked potential recordings
      in the surgically anaesthetized patient appeared to be more stable compared to
      our earlier findings using transient visual evoked potentials. However, further
      efforts are necessary to improve the stability of the recordings during surgery
      and thus allow for a more reliable intraoperative monitoring of visual pathways
      in routine clinical practice.

PMID- 15248622
TI  - Detection of causal relationships between factors influencing adverse side
      effects from anaesthesia and convalescence following surgery: a path analytical
      approach.
AB  - BACKGROUND AND OBJECTIVE: The anaesthesiologist's preoperative interview with the
      patient is important in preparing the patient for surgery. Its potential
      protective influence on adverse side-effects from anaesthesia and convalescence
      is rarely investigated within the context of other perioperative factors.
      Structural equation modelling allows detection and quantification of all causal
      relationships and mediator effects in multivariate models. Therefore, this method
      is presented as a tool and applied to discover the influence of the preoperative
      interview within socio-demographic variables and duration of surgery on
      complaints and recovery after anaesthesia. METHODS: The influence of individual
      satisfaction with the anaesthesiologist's preoperative interview on postoperative
      events such as nausea/vomiting, difficulties in recovering from anaesthesia,
      experience of postoperative pain, physical discomfort and satisfaction with
      convalescence expressed by the patient was analysed by means of structural
      equation modelling. The variables gender, age and duration of surgery were also
      included as predictors in the analyses. The model in the total sample of 710
      patients was then analysed for structural differences between groups treated
      either with propofol (n = 204) or with isoflurane + nitrous oxide (n = 267) for
      maintenance of anaesthesia. RESULTS: The model revealed that the
      anaesthesiologist's preoperative interview in combination with associated
      mediating side-effects explains 45% of the variance of 'feeling physical
      discomfort' and 18% of the variance of 'satisfaction with convalescence'. The
      same model could be fitted in the propofol and the isoflurane + nitrous oxide
      group. Moreover, the structure and the strength of causal relations between
      variables were identical in the two groups. CONCLUSIONS: The anaesthesiologist's
      efforts to improve the interview with the patient by more reassuring and proper
      information will result in less side-effects from anaesthesia and better recovery
      from surgery. It could be demonstrated that structural equation modelling is a
      powerful tool for detection of causal relationships and mediator effects in
      perioperative medicine.

PMID- 15248623
TI  - Cricoid pressure: a simple, yet effective biofeedback trainer.
AB  - BACKGROUND AND OBJECTIVE: Only regular training of anaesthetic personnel ensures
      safe and reliable application of cricoid pressure during rapid sequence induction
      of anaesthesia. Previously described training devices are either complicated, too
      expensive and usually unavailable, or they are very simple and do not correctly
      simulate the process of applying cricoid force. We designed and tested a cricoid
      pressure trainer with real-time display of applied force. The device is easy to
      assemble at relatively little cost with material widely available. It allows
      effective biofeedback training of the force required during the Sellick manoeuvre
      and can be used for routine staff assessment. METHODS: Thirty-six anaesthesia
      assistants were assessed for their correct application of cricoid pressure.
      Previous training in, and knowledge of, applying cricoid pressure was first
      evaluated by a questionnaire. We designed a model for testing the application of
      cricoid force. Pre-training cricoid forces were obtained by asking the subjects
      to apply 'awake' (10 N = 1.020 kg) and 'asleep' (30 N = 3.060 kg) cricoid
      pressure on our model while blinded to the actual pressure produced. The
      volunteer was then trained to apply correct pressure employing real-time
      biofeedback. Post-training values were later determined with the subject again
      blinded to the actual applied pressure. RESULTS: Post-training performance showed
      significant improvement in the application of the correct cricoid force (P <
      0.0005). Only 8% (3/36) of subjects applied incorrect 'awake' cricoid pressure
      after training vs. 56% (20/36) before training. All participants applied correct
      'asleep' cricoid pressure after training vs. 72% (26/36) failing before training.
      CONCLUSIONS: Our biofeedback cricoid pressure trainer is effective in the
      assessment and training of correct cricoid pressure application by anaesthetic
      personnel.

PMID- 15248624
TI  - Air leakage around endotracheal tube cuffs.
AB  - BACKGROUND AND OBJECTIVE: To compare the recently introduced Microcuff
      endotracheal tube with conventional tubes in respect of the cuff pressures
      required to prevent air leakage. METHODS: The following tubes (ID 7.0mm) were
      compared: Microcuff HVLP ICU, Mallinckrodt HiLo, Portex Profile Soft Seal, Rusch
      Super Safety Clear and Sheridan CF. Fifty patients undergoing endotracheal
      intubation with a cuffed tube of internal diameter 7.0 mm were studied. Tracheas
      were intubated using one of the endotracheal tubes in random order. Cuff pressure
      to prevent air leakage at standardized ventilator setting (peak inspiratory
      pressure 20 cmH2O/PEEP 5 cmH2O/respiratory rate 15 breaths min(-1)) was assessed
      by auscultation of audible sounds at the mouth. Patients characteristics and cuff
      pressures from each brand were compared to the Microcuff group using the Mann
      Whitney U-test (P < 0.05 was chosen as the level of statistical significance).
      RESULTS: Patients' median age (range) was 14.2 (12.0-17.1) yr, body weight 57.5
      (40.0-81.9) kg and length 164.9 (146.5-190.0) cm. No significant differences in
      patients' characteristics were found between groups. Mean cuff pressure (all
      tubes) required for air sealing was 19.1 (8-42) cmH2O. The Microcuff tube
      required significantly lower sealing pressures (9.5 (8-12) cmH2O) compared to the
      other brands of endotracheal tube (P < 0.05, Mann-Whitney U-test). CONCLUSION:
      The Microcuff endotracheal tube with its ultra-thin polyurethane cuff membrane
      required the lowest sealing pressure to prevent air leakage. These features are
      potentially of interest for long-term intubated patients and for cuffed
      endotracheal tubes in children, allowing tracheal sealing at lower cuff pressures
      implying less damage to the trachea.

PMID- 15248625
TI  - Low-dose combined spinal-epidural anaesthesia vs. conventional epidural
      anaesthesia for Caesarean section in pre-eclampsia: a retrospective analysis.
AB  - BACKGROUND AND OBJECTIVE: Epidural anaesthesia is the preferred technique of
      anaesthesia for Caesarean section in pre-eclampsia. Spinal anaesthesia is
      considered by some as a safe and effective alternative, which is especially
      useful in emergency situations. Combined spinal-epidural anaesthesia, using low
      doses of local anaesthetics with opioids, is effective and reduces the incidence
      of hypotension in normal pregnancy. We performed a retrospective chart analysis
      to evaluate the effects of combined spinal-epidural anaesthesia on maternal
      haemodynamics and fetal outcome compared to conventional epidural anaesthesia.
      METHODS: A retrospective anaesthesia chart analysis of all pre-eclamptic patients
      who underwent Caesarean section over a 4 yr period was performed. Patient
      characteristic, obstetric, haemodynamic, fetal and neonatal data were gathered
      and analysed according to the anaesthetic technique used. RESULTS: Seventy-seven
      pre-eclamptic parturients undergoing Caesarean section were identified (26 women
      were severely pre-eclamptic and 51 demonstrated mild pre-eclampsia). Epidural
      anaesthesia was performed in 62 patients and combined spinal-epidural anaesthesia
      was performed in 15. No differences in patient characteristic and obstetric data
      were noted. Highest mean arterial pressure prior to anaesthesia was comparable
      between the groups (epidural: 106 +/- 12 vs. combined spinal-epidural
      anaesthesia: 109 +/- 18 mmHg) as well as the lowest recorded mean arterial
      pressure following anaesthesia (epidural: 93 +/- 13 vs. combined spinal-epidural
      anaesthesia: 98 +/- 17 mmHg). In the combined spinal-epidural anaesthesia group
      more ephedrine was used compared to the epidural group (14.6 +/- 4.4 vs. 3.6 +/-
      4.6 mg, P < 0.05). However, more lactated Ringer's was used in the epidural
      group. Umbilical artery pH was lower in the epidural group (7.26 +/- 0.01 vs.
      7.29 +/- 0.02, P < 0.05). Similar results were noted in 26 severely pre-eclamptic
      patients. Seven women underwent combined spinal-epidural anaesthesia and 19
      underwent epidural anaesthesia in the severely pre-eclamptic group. Also more
      ephedrine was used in the combined spinal-epidural anaesthesia group. A tendency
      towards a lower umbilical artery pH was observed in the epidural group but this
      difference did not reach statistical significance. CONCLUSIONS: Combined spinal
      epidural anaesthesia appears to be safe as anaesthetic technique for pre
      eclampsia and severe pre-eclampsia. However, it is important to consider the
      retrospective design of the study and the large number of epidural anaesthetics
      performed.

PMID- 15248626
TI  - The systemic absorption and disposition of levobupivacaine 0.5% after epidural
      administration in surgical patients: a stable-isotope study.
AB  - BACKGROUND AND OBJECTIVE: Absorption and disposition kinetics can be studied with
      a stable-isotope method. The aim of this study was to validate a stable-isotope
      method for levobupivacaine and to derive the relevant pharmacokinetics after
      epidural administration. METHODS: Eight volunteers (18-32 yr) received
      approximately 23 mg of both levobupivacaine and deuterium-labelled
      levobupivacaine simultaneously by intravenous infusion. Venous blood samples were
      taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5%
      (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg
      deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial
      blood samples were collected for 24 h. Plasma concentrations were determined
      using liquid chromatography-mass spectrometry. Plasma concentration-time data
      were analysed by compartmental and non-compartmental analysis. RESULTS: Based on
      the ratio of the normalized areas under the curve of unlabelled and deuterium
      labelled levobupivacaine in volunteers, as determined by both compartmental (mean
      ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02,
      90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical
      patients the elimination half-life (mean +/- SD: 196 +/- 65 min), total body
      clearanc (349 +/- 114 mL min(-1)) and volume of distribution at steady state (56
      +/- 14 L), derived by compartmental analysis, were similar to those obtained by
      non-compartmental analysis. The absorption was bi-phasic. The fractio absorbed
      and half-life of the fast absorption process were 0.22 +/- 0.06 and 5.2 +/- 2.7
      min, respectively. Th values for the slow absorption process were 0.84 +/- 0.14
      and 386 +/- 91 min, respectively. CONCLUSIONS: D3-levobupivacaine is
      pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to
      study the absorption and disposition kinetics after perineural administration of
      levobupivacaine in a single experiment.

PMID- 15248627
TI  - Ibuprofen vs. acetaminophen vs. ibuprofen and acetaminophen after
      arthroscopically assisted anterior cruciate ligament reconstruction.
AB  - BACKGROUND AND OBJECTIVE: The analgesic potency of non-steroidal anti
      inflammatory drugs and acetaminophen are still being debated. We have assessed
      the relative analgesic effect of ibuprofen, acetaminophen or the combination of
      both after orthopaedic surgery. METHODS: Sixty-one ASA I patients, scheduled for
      an elective anterior cruciate ligament reconstruction under general anaesthesia
      were randomized, in a double blind fashion, into one of three groups. The
      ibuprofen group (n = 17) received ibuprofen 800 mg orally 1 h before operation
      and again at 6 and 12 h after the initial dose. The acetaminophen group (n = 20)
      received of acetaminophen 1 g orally at the same time intervals. The combination
      group (n = 24) received both ibuprofen 800 mg and acetaminophen 1 g. Surgery was
      performed under general anaesthesia with propofol and fentanyl for induction and
      maintenance with propofol and nitrous oxide in oxygen. The patients were
      monitored for 24 h thereafter, and the following variables were assessed: pain by
      visual analogue and verbal scales, need for rescue intravenous opioid analgesia
      (i.e. ketobemidone) and adverse events. RESULTS: The ibuprofen group and the
      combination group experienced significantly less pain during the first 6 h after
      surgery than the acetaminophen group using the visual analogue and the verbal
      scales. The acetaminophen group also had a significantly higher average
      consumption of opioids during the first 6 and 24 h. There were no significant
      differences between the ibuprofen group and the combination group in respect of
      experienced pain or consumption of rescue analgesia. The incidence of side
      effects, postoperative haemoglobin concentration and renal function, judged by
      creatinine clearance, were identical between the groups. CONCLUSION: Ibuprofen
      800 mg thrice daily reduced pain to a greater degree than acetaminophen 1 g
      thrice daily, after anterior cruciate ligament reconstruction under general
      anaesthesia. The combination of acetaminophen and ibuprofen did not provide any
      superior analgesic effect.

PMID- 15248628
TI  - Comparative assessment of the effects of alfentanil, esmolol or clonidine when
      used as adjuvants during induction of general anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: This randomized, double-blinded, prospective study
      compared the effects of clonidine, esmolol or alfentanil on the level of hypnosis
      and haemodynamic responses to intravenous induction of anaesthesia and
      endotracheal intubation. METHODS: Forty-five patients scheduled for elective
      surgery were allotted to one of three groups. They were given either alfentanil 3
      microg kg(-1) min(-1) (n = 15); esmolol 1 mg kg(-1) min(-1) (n = 16) or clonidine
      3 microg kg(-1) (n = 14) as a 10 min infusion. The infusions of alfentanil and
      esmolol, but not of clonidine, were maintained during endotracheal intubation.
      Anaesthesia was induced with midazolam (2 mg) and thiopental as required to
      suppress the eyelash reflex. Atracurium (0.5 mg kg(-1)) was given to produce
      neuromuscular block. Mean arterial pressure, heart rate, and bispectral index
      were recorded on arrival (baseline), after study drug infusion, after injecting
      midazolam and thiopental, as well as after endotracheal intubation. ANOVA and
      chi2-test were used for analysis. RESULTS: Blood pressure, heart rate and the
      bispectral index were unaltered by the study drugs, but thiopental requirements
      were reduced by alfentanil and clonidine (P < 0.014). Mean arterial pressure
      values (mean +/- standard error of mean) in the alfentanil, esmolol and clonidine
      groups were: baseline: 107.8 +/- 3.8; 106.6 +/- 3.9; 103.4 +/- 3.7 mmHg; after
      thiopental: 74.0 +/- 4.2; 85.6 +/- 4.3; 94.2 +/- 4.1 mmHg and after endotracheal
      intubation: 91.7 +/- 5.3; 114.1 +/- 6.9; 123.6 +/- 5.6 mmHg, respectively (two
      way ANOVA, P < 0.001). Mean arterial pressure changed significantly after
      intubation from baseline (P < 0.001) after alfentanil (-15%) and clonidine (+20%)
      but not after esmolol (+7%), while the changes between pre- and postintubation
      values were similar in all groups (24-33% increase). The bispectral index
      indicated that all patients had an adequate level of hypnosis, but the
      variability was higher in the esmolol group (P < 0.002). CONCLUSIONS: None of the
      study drugs blocked the increase in mean arterial pressure induced by
      endotracheal intubation, but esmolol provided better overall haemodynamic
      stability. All groups had an adequate level of hypnosis.

PMID- 15248629
TI  - Closed-system anaesthesia for laparoscopic surgery: is there a risk for carbon
      monoxide intoxication?
AB  - BACKGROUND AND OBJECTIVE: One of the complications of laparoscopic surgery is
      carbon monoxide production during electrocautery. The aim of our study was to
      ascertain the relationship between intraperitoneal and alveolar concentrations of
      carbon monoxide and systemic carboxyhaemoglobin in patients undergoing
      laparoscopic cholecystectomy and anaesthetized with a closed system, where the
      carbon monoxide excreted through the lungs is accumulated in the circuit and thus
      re-inhaled. METHODS: Nine consecutive patients undergoing laparoscopic
      cholecystectomy were studied. Patients' lungs were ventilated with a closed
      anaesthesia breathing system (Physioflex). Measurements were taken after
      establishing pneumoperitoneum (baseline) and at 5, 15 and 30 min after starting
      electrocautery. RESULTS: Mean duration of pneumoperitoneum was 42 +/- 13 min with
      cumulative electrocautery time of 2.4 +/- 1.8 min. Intraperitoneal carbon
      monoxide concentrations increased significantly at 5, 15 and 30 min reaching peak
      values of 481 +/- 151 ppm at 15 min. No significant differences were found in
      alveolar carbon monoxide and carboxyhaemoglobin concentrations with respect to
      baseline. CONCLUSIONS: No significant increase in carboxyhaemoglobin is produced
      during laparoscopic surgery, even under closed-system anaesthesia without
      pulmonary carbon monoxide elimination. This is most likely due to a low
      peritoneal absorption of carbon monoxide. We conclude that in adult patients, no
      carbon monoxide intoxication is caused if reasonable periods of electrocautery
      are used and the intraperitoneal gas is regularly renewed.

PMID- 15248630
TI  - General anaesthesia combined with bilateral paravertebral blockade (T5-6) vs.
      general anaesthesia for laparoscopic cholecystectomy: a prospective, randomized
      clinical trial.
AB  - BACKGROUND AND OBJECTIVE: The efficiency of bilateral paravertebral blockade
      combined with general anaesthesia (active) vs. general anaesthesia alone
      (control) in reducing postoperative pain following laparoscopic cholecystectomy
      was evaluated using a prospective randomized study design. METHODS: Patients were
      randomly assigned to either group. Nerve-stimulator guided paravertebral blockade
      at the T5-6 level was performed with a local anaesthetic mixture (0.30 mL kg(
      1)). Twenty millilitres of the mixture contained lidocaine 2% 6 mL; lidocaine 2%
      6 mL with epinephrine 1/200 000; bupivacaine 0.5% 5 mL; fentanyl 1 mL (50 microg
      mL(-1)) and clonidine 2 mL (150 microg mL(-1)). Postoperative pain and
      consumption of opioids were assessed during the first 72 h. RESULTS: Two-times 30
      patients were analysed. Patient characteristics data, and pre- and peroperative
      variables were similar in both groups. Mean pain scores visual analogue scale
      were significantly less with active compared with control (P < 0.05) at 6h (1.56
      +/- 1.58 vs. 4.78 +/- 1.67), at 12 h (1.52 +/- 1.58 vs. 3.81 +/- 1.63), at 24 h
      (1.16 +/- 1.34 vs. 2.71 +/- 1.50), at 36h (0.68 +/- 1.02 vs. 2.29 +/- 1.41), at
      48h (0.60 +/- 1.04 vs. 1.61 +/- 1.33) and at 72 h (0.40 +/- 0.86 vs. 1.19 +/-
      1.16). The number of patients consuming supplemental analgesics was significantly
      less (P < 0.05) with active compared with control, at 6 h (6 vs. 29), at 12 h (2
      vs. 26), at 24 h (1 vs. 23) and at 36 h (2 vs. 15). More patients were free from
      nausea (P < 0.05) with active compared with control at 6 h (23 vs. 9) and at 12 h
      (29 vs. 19). CONCLUSION: When used as a complement to general anaesthesia,
      bilateral nerve-stimulator guided paravertebral blockade with lidocaine,
      bupivacaine, fentanyl and clonidine may improve postoperative pain relief.

PMID- 15248631
TI  - Effect of repeat laryngoscopy on intraocular pressure.

PMID- 15248632
TI  - Are anaesthesiologists comfortable with spinal anaesthesia for themselves?

PMID- 15248633
TI  - Central anticholinergic syndrome in the intensive care unit.

PMID- 15248634
TI  - Why must vascular surgery have its own independent board?

PMID- 15248635
TI  - Does the Vascular Surgery Board of the American Board of Surgery work?
AB  - Recommendations to form an independent American Board of Vascular Surgery were
      made several years ago by leaders in vascular surgery. All major vascular
      societies in the United States voted by majority rule to approve the formation of
      this organization. Although the Vascular Surgery Board of the American Board of
      Surgery is well intentioned, its focus and intentions are outdated because it is
      subservient to the American Board of Surgery.

PMID- 15248636
TI  - The American Board of Vascular Surgery and the law: fact and fiction.
AB  - The need for the establishment of an independent American Board of Vascular
      Surgery (ABVS) remains controversial. The controversy involves both medical and
      legal issues. These issues include medical malpractice, the attempt to create a
      "monopoly" by vascular surgeons, and the hospital credentialing of surgeons to
      perform vascular procedures. In this article, the legal impact of an independent
      ABVS on the filing of medical malpractice suits against vascular surgeons is
      explored. In addition, the legal criteria necessary to establish a monopoly, as
      well as criteria for hospital credentialing, are also reviewed. The results of
      this legal analysis are, first, that the establishment of an independent ABVS may
      well lead to a decrease in the number of frivolous lawsuits filed against
      vascular surgeons. Second, the establishment of an ABVS does not constitute the
      creation of a monopoly. Finally, hospital credentialing should not, and will not,
      be directly affected by the establishment of an independent ABVS.

PMID- 15248637
TI  - Vascular surgery: a contributor to the family of American surgery.

PMID- 15248638
TI  - Combined open and endovascular treatment of complex aortic disease.
AB  - The purpose of this article is to report whether combined open and endovascular
      treatment could be applied in patients with complex aortic disease. A
      retrospective study including four patients with complex aortic disease was
      undertaken. In all patients, extra-anatomic bypass to the visceral arteries was
      made through a laparotomy while the aortic lesion was repaired by stent grafting.
      One patient died on the first postoperative day and another died 3 months after
      treatment from a myocardial infarction. The other two patients were alive 13 and
      34 months after treatment, respectively. However, a patient treated for a
      ruptured thoracoabdominal type 2 aneurysm on the basis of a dissection suffers
      from postoperative paraplegia. The combination of open surgery with extra
      anatomic bypass to visceral arteries and stent grafting could be an option for
      the treatment of patients with complex aortic disease, especially in high-risk
      cases in which more extensive open surgery is contraindicated.

PMID- 15248639
TI  - Noninvasive intrasac pressure measurement and the influence of type 2 and type 3
      endoleaks in an animal model of abdominal aortic aneurysm.
AB  - The objective of this study was to noninvasively detect pressure changes within
      an excluded aneurysm sac in an animal model of abdominal aortic aneurysm (AAA)
      and to study the influence of type 2 and 3 endoleaks. A porcine model of AAA that
      allows for the creation of type 2 and 3 endoleaks was used. A miniaturized
      pressure monitoring device (3 x 9 x 1.5 mm; Remon Medical Technologies, Caesarea,
      Israel) was implanted within the surgically created and excluded aneurysm sac.
      The pressure monitoring device is an ultrasound-based system that allows for
      pressure measurements in a noninvasive, transcutaneous fashion. In addition,
      catheter-based pressures were taken within the aorta and directly in the AAA sac.
      Noninvasive measurements were taken in a transcutaneous fashion between the
      initial operation and the time of sacrifice, when the type 3 endoleak was created
      (2 weeks). The median mean arterial pressure was 66 mm Hg (range 55-120 mm Hg; N
      = 8). The median noninvasive sac pressure with a type 2 endoleak was 48 mm Hg
      (range 39-90 mm Hg; N = 8) and was almost identical to the catheter-based
      measurements. Noninvasive pressures could be measured as early as postprocedure
      day 1. Two animals had follow-up that suggested closure of the type 2 endoleak
      during the observation period. With the creation of the type 3 endoleak, the
      catheter and noninvasive sac pressure and waveform changed from a flatline trace
      to a higher-pressure pulsatile trace (median 54 mm Hg; range 46-81 mm Hg; N = 8),
      reproducing the arterial pressure and waveform. This is the first study, to our
      knowledge, that demonstrates the efficacy of a noninvasive, miniaturized pressure
      monitoring device in identifying pressure changes in an excluded aneurysm sac
      with type 2 and type 3 endoleaks. This technology holds great promise for follow
      up of patients and identification of sac pressure changes after EVAR and may
      allow a change in the current follow-up strategy.

PMID- 15248640
TI  - Endovascular abdominal aortic aneurysm repair in patients with challenging
      anatomy: utility of the hybrid endograft.
AB  - Commercially available aortic stent grafts differ in construction and clinical
      advantage such that creating hybrid endografts by combining components from
      different manufacturers is sometimes useful. We describe a multicenter experience
      using hybrid endografts to treat patients with challenging anatomy. Hospital
      records and office charts were reviewed from four institutions. Hybrid endografts
      were defined as those with two types of covered stents in continuity to treat an
      abdominal aortic aneurysm (AAA). Indications for hybrid grafts were defined by
      type of endoleak and whether an endoleak was expected or unexpected as determined
      by the preoperative radiographic evaluation. Endpoints include intraoperative
      endoleaks, late endoleaks, change in aneurysm size, and rupture. Hybrid
      endografts were used to treat AAA (endovascular aneurysm repair [EVAR]) in 90
      patients, representing 7.9% of the total multicenter experience. In 7 patients
      (7.8%), a hybrid graft construction as a secondary procedure successfully
      corrected a type 1 endoleak. In the remaining 83 patients (92.2%), hybrid grafts
      were created at the time of original EVAR to treat expected challenging anatomy
      or unexpected endoleaks. Hybrid endografts corrected 88 (97.8%) type 1 endoleaks,
      but 2 patients (2.2%) persisted with a proximal type 1 leak requiring conversion.
      During follow-up of 1 to 24 months, computed tomography and ultrasound
      surveillance, available for 73 patients (81.1%), detected one unresolved distal
      type 1 (1.1%) and seven type 2 (7.8%) endoleaks. Aneurysm size decreased at least
      0.5 cm in 23 of 50 patients (46.0%) at 6 months and in 19 of 31 patients (61.3%)
      at 12 months. Aneurysm size increased at least 0.5 cm in 4 of 50 patients (8.0%)
      at 6 months and in 1 of 31 patients (3.2%) at 12 months. There were no ruptures.
      Hybrid endografts have favorable early and intermediate results in the treatment
      of AAA. Long-term follow-up will be needed to confirm the absence of significant
      adverse biomaterial interaction and the effect on AAA exclusion. We advocate the
      use of hybrid endografts as endovascular therapy for patients whose anatomy may
      be unsuitable for a single endograft type.

PMID- 15248641
TI  - Clinically diagnosed nonocclusive mesenteric ischemia after cardiopulmonary
      bypass: retrospective study.
AB  - This retrospective study evaluates our experience with clinically diagnosed
      nonocclusive mesenteric ischemia after cardiopulmonary bypass. Twenty-three of
      3,600 consecutive patients suffered from splanchnic malperfusion. Symptoms
      developed between day 2 and 6 postoperatively in 18 of 23 patients. Four of 23
      patients had no abdominal symptoms. Laboratory evaluation revealed significantly
      higher serum lactate and creatine phosphokinase levels in the 18 symptomatic
      patients compared with those of a control group. Arteriography was performed in
      20 cases and revealed nonocclusive splanchnic hypoperfusion. Risk factors for
      development of mesenteric ischemia include arrhythmias and low cardiac output.
      Patients with angiographically proven nonocclusive mesenteric ischemia were
      treated with intra-arterial bolus injection and subsequent intra-arterial
      infusion of tolazoline combined with heparin sodium. The overall mortality rate
      was 30% (7 of 23). Infusion therapy with tolazoline and heparin seems to be a
      successful treatment modality for clinically diagnosed mesenteric ischemia.

PMID- 15248642
TI  - Mortality after peripheral bypass surgery: value of a mortality scoring system in
      evaluating the quality of care.
AB  - The objective of this study was to determine the role of a mortality registration
      in the quality control of patients who died after peripheral bypass surgery. We
      developed a mortality registration to classify causes of death, to evaluate
      shortcomings in treatment, and to determine the extent of agreement between pre-
      and postmortem findings. In a 10-year period, 28 of the 1,022 patients (2.7%) who
      underwent peripheral arterial reconstruction died. Fifty-three percent of the
      patients died owing to postoperative complications, most frequently a myocardial
      infarction. A shortcoming in the medical treatment was observed in only one
      patient. Forty-three percent of the relatives gave permission for an autopsy. In
      only two cases, the autopsy report revealed a myocardial infarction that had
      remained unnoticed during the clinical course. In this selected group of patients
      undergoing a peripheral bypass operation, the causes of death and the
      shortcomings in medical care could usually be identified without the help of
      autopsy data.

PMID- 15248643
TI  - Total laparoscopic aortomesenteric bypass.
AB  - We describe what we believe to be the first case of C-loop aortomesenteric total
      laparoscopic bypass. This bypass was combined with a total laparoscopic
      aortofemoral bypass. The approach to the superior mesenteric artery used a
      partial left medial visceral rotation after a left retrocolic dissection.

PMID- 15248644
TI  - Delayed paraplegia following infrarenal abdominal aortic endograft placement:
      case report and literature review.
AB  - The treatment of abdominal aortic aneurysms (AAAs) has changed over the past 12
      years, with increased numbers of endovascular procedures being performed. Early
      morbidity is decreased following endovascular abdominal aortic aneurysm repair
      (EVAR) compared with open repair, and long-term studies of EVAR have focused on
      freedom from death, rupture, and conversion to open repair. Other less commonly
      encountered complications of EVAR are rarely reported. For instance, spinal cord
      ischemia (SCI) is a devastating complication infrequently seen after open AAA
      repair. This report discusses a case of delayed paraplegia after EVAR and reviews
      the pertinent literature. The incidence of SCI after EVAR is similar to open
      repair, but the mechanisms may be different. Atheroembolization and occlusion of
      pelvic inflow appear to be the predominant etiologies for SCI after EVAR. Careful
      consideration of the potential for SCI should be made in elderly patients
      undergoing EVAR, particularly if difficult arterial anatomy is present.

PMID- 15248645
TI  - Intraoperative venous balloon angioplasty during surgical thoracic outlet
      decompression in Paget-Schrotter syndrome.
AB  - The management of primary subclavian-axillary vein thrombosis is controversial.
      Indications and time of operative or endovascular intervention after successful
      thrombolysis remain unresolved. To improve the long-term functional outcomes in
      patients with primary subclavian-axillary vein thrombosis, early reestablishment
      of venous patency and prevention of recurrent thrombosis are required. We present
      a case in which, after catheter-directed thrombolysis, positional venography
      showed costoclavicular compression of the subclavian vein. At the time of
      surgical thoracic outlet decompression, transluminal venous angioplasty was
      performed.

PMID- 15248646
TI  - Primary endothelial sarcoma of the thoracic aorta.
AB  - Primary malignant tumors of the aorta are extremely rare. The case of a 64-year
      old woman who presented with peripheral embolism to both femoropopliteal arteries
      is reported. The search for a source revealed a polypoid lesion severely
      narrowing the lumen of the distal thoracic aorta. Differential diagnosis included
      thrombus and primary aortic tumor. Extirpation of the tumorous lesion was
      performed. Histologic examination revealed intimal aortic sarcoma of endothelial
      cell origin. Although the liver was the only site of suspected metastases at the
      time of operation, during the 18-month follow-up until the patient's death,
      generalized metastatic spread had developed. This case report thus demonstrates
      the generally poor prognosis of this rare variety of aortic sarcoma, in
      particular when symptoms have already occurred.

PMID- 15248647
TI  - Insect fauna associated with sugarcane plantations in Sri Lanka.
AB  - A survey conducted over 13 years (1986-1999) in sugarcane plantations in Sri
      Lanka to identify insects associated with sugarcane recorded a total of 103
      insect species comprising Coleoptera (31 spp.), Dictyoptera (2 spp.), Diptera (5
      spp.), 12 Heteroptera (12 spp.), Homoptera (18 spp.), Hymenoptera (7 spp.),
      Isoptera (3 spp.), Lepidoptera (13 spp.), Orthoptera (9 spp.), and one species
      each of Thysanoptera, Nuroptera and Trichoptera. Among them were forty-six
      species of sugarcane pests. In addition, 27 species of natural enemies of
      sugarcane pests belonging to the orders Coleoptera, Diptera and Hymenoptera were
      identified Epiricania melanoleuca (Fletcher) introduced into Sri Lanka from
      Pakistan in 1991 for the control of the sugarcane planthopper was also recorded.
      Five new pest species previously not recorded from sugarcane in Sri Lanka have
      been identified.

PMID- 15248648
TI  - Pre-administration of beta-carotene protects tissue glutathione and lipid
      peroxidation status following exposure to gamma radiation.
AB  - The present study has been aimed to investigate the protective effect of beta
      carotene against radiation-induced oxidative stress in mice tissues using lipid
      peroxidation and glutathione (GSH) as end points. Fourteen days oral priming
      administration of beta-carotene (35 mg/kg body weight) followed by an acute dose
      of gamma radiation (5 Gy) inhibited the augmented level of thiobarbituric acid
      reactive substance (TBARS) and a statistically significant protection against GSH
      depletion. Results evaluated from this study clearly indicate the antioxidative
      property of beta-carotene against gamma radiation, which is suggestive of free
      radical scavenging and singlet oxygen quenching.

PMID- 15248649
TI  - Influence of pH, salt concentration and temperature on the growth of Aeromonas
      hydrophila.
AB  - The influence of environmental factors on the growth of Aeromonas hydrophila was
      investigated Four isolates (AH 37, AH 79, AH 86 and AH 100) were exposed to
      various environmental factors such as pH, salt concentration and temperature in
      laboratory condition. All the four isolates showed more or less similar growth at
      pH 7.0, 8.0 and 9.0 at 30 degrees C and 5 degrees C. At pH 5.0, 6.0 and 10.0, the
      log number of cells was found to be lesser than that of pH 7.0, 8.0 and 9.0 at
      both 30 degrees C and 5 degrees C. The results of the influence of salt
      concentration on the growth of Aeromonas hydrophila revealed that NaCl
      concentration of 0.5%, 1.0% and 2.0% favored the growth of this organism at both
      30 degrees C and 5 degrees C. Increase in the salt concentration resulted in the
      growth of the decrease of this organism. Three percentages and 4% salt
      concentration moderately supported the growth of the organisms in the medium
      whereas at 5.0% NaCl concentration, there was no growth. Moderate growth of A.
      hydrophila at 5 degrees C is an interesting observation. The ability to grow at
      salt concentration between 0.5%, 4.0% under acidic and alkaline conditions pose a
      problem in the preservation of seafoods. These criteria may account for modified
      preservation techniques.

PMID- 15248650
TI  - Fresh water fishes as indicators of Kaveri River pollution.
AB  - The survey of fish fauna in Kaveri River at polluted and unpolluted sites
      revealed a direct effect on the distribution of fishes in that 14 species were
      observed in unpolluted site and only 6 species in polluted site. Further, the
      haemotological parameters like RBC, WBC and haemoglobin content increased in
      fishes collected from polluted site whereas the organic constituents of muscle
      decreased in the above fishes when compared to the fishes of unpolluted site. The
      reason for the above changes is discussed.

PMID- 15248651
TI  - Insecticidal activity of the plant Phyllanthus amarus against Tribolium
      castaneum.
AB  - The plant Phyllanthus amarus is used as folk medicine since the year 1800 and has
      been established for its important medicinal properties particularly for liver
      ailments. The present communication explores the insecticidal activity of
      ethanolic extract of aerial and root parts of this plant against stored grain
      pest Tribolium castaneum. LC 50 values of ethanolic aerial part were 895.77,
      473.91, 279.89 and 260.85 microg/cm2, while 512.62, 376.96, 248.88 and 209.79
      microg/cm2 for ethanolic root part at the exposure of 3, 5, 7, 9 and 11 days
      respectively. Ethanolic root extract possessed significant insecticidal activity
      against T. castaneum.

PMID- 15248652
TI  - Heavy metals alter photosynthetic pigment profiles as well as activities of
      chlorophyllase and 5-aminolevulinic acid dehydratase (ALAD) in Amaranthus lividus
      seedlings.
AB  - Varied concentrations of PbCl2 and CdCl2 in the germinating media reduced the
      total chlorophyll and carotenoid contents in primary leaves of Amaranthus lividus
      seedlings (168 h old). When chlorophyll a and chlorophyll b contents were
      measured separately, greater loss of chl b than chl a under the identical
      conditions of heavy metal treatment was observed In addition, the loss of total
      chlorophyll was more than carotenoids under the same magnitude of heavy metal
      treatment. The effect of heavy metal treatment at germination stage was further
      studied on chlorophyll accumulation in primary leaves in relation to the
      activities of 5-aminolevulinic acid dehydratase (ALAD) and chlorophyllase. The
      activities of ALAD gradually diminished in response to both the heavy metals in a
      concentration-guided manner, while the activities of chlorophyllase did not
      exhibit any significant change.

PMID- 15248653
TI  - Effect of mercuric chloride on circulating hormones in adult albino rats.
AB  - The effect of mercuric chloride at two different doses, 0.5 mg/kg body weight
      (low dose), 1 mg/kg body weight (high dose), for 30 days, was seen on the
      circulating hormones in the mature male albino rats. Testosterone level was
      markedly decreased in the low dose (P < 0.01) and high dose (P < 0.001) treated
      animals. The level of luteinizing hormone (LH) was also reduced in the low dose
      (P < 0.01) as well as in the high dose (P < 0.001) treated animals. However,
      follicle stimulating hormone (FSH) and prolactin (PRL) levels were found to be
      decreased only in the high dose (P < 0. 05) treated animals and no change was
      observed in the low dose treated animals. The changes in the hormone levels
      caused by the mercuric chloride treatment suggest the dysfunction of pituitary
      testicular axis.

PMID- 15248654
TI  - Observations on the histological alterations in various tissues of EUS affected
      fish, Channa striatus (Bloch).
AB  - Histopathological investigations have been made on the skin, liver, kidney and
      intestine of, (EUS) affected fish, Channa striatus and following anomalies have
      been observed. Varying degree of degeneration has been observed in the epidermis,
      dermis, hypodermis and underlying musculature. In all the cases, the skin lost
      the scales and epidermis completely at the site of infection. The dermis along
      with hypodermis showed the signs of necrosis. Necrosis also took place in
      subcutaneous layer underlying the hypodermis. Necrotization and formation of
      granulomas can clearly be seen in circular and longitudinal muscle layers. The
      liver exhibited the loosening of tissue and distension in cell bodies. While in
      case of kidney, shrinkage took place in all the components. Similarly, the
      intestinal villi got necrotised alongwith their constituent elements.

PMID- 15248655
TI  - These studies were conducted to assess the effects of lead toxicity on
      exploratory behavior and running. Effects of lead on exploratory behavior and
      running speed in the shrew, Blarina brevicauda (Insectivora).
AB  - These studies were conducted to assess the effects of lead toxicity on
      exploratory behavior and running speed in the short-tailed shrew, Blarina
      brevicauda. Shrews from the experimental group received 25 mg/kg/day of lead
      acetate in their drinking water for a period of 90 days. Control subjects
      received sodium acetate. Exploratory behavior was determined using a computerized
      activity chamber where movements of test subjects broke infrared beams projected
      onto the floor of the apparatus. Time spent (sec) in exploration was recorded
      over eight 6-min intervals. Running speed (km/hr) was measured in a
      microprocessor-controlled rectangular racetrack fitted with photocell timers.
      With respect to time spent in exploration, there were significant differences
      between lead-exposed (20.5-23.9 sec per 6-min testing session) and control
      subjects (6.8-8.1 sec) after the sixth testing interval in the activity chamber.
      With respect to maximal running speed, control subjects ran significantly faster
      (mean: 14.8 km/hr) than their lead-exposed counterparts (5.83 km/hr). Lead
      exposed animals exhibited hyperactivity and increased random locomotor movements.
      They would frequently bump into the walls and their movements were more random.
      Controls typically ran along the racetrack in a straight line. These results
      represent the first data for the effects of lead exposure on exploratory behavior
      and running speed for shrews.

PMID- 15248656
TI  - Evaluating the seasonal changes of water quality of the Degirmendere and Galyan
      Rivers (Trabzon, Turkey).
AB  - The Degirmendere and Galyan (Degirmendere tributary) Rivers that discharge their
      water into the Black Sea are important watersheds in the northeastern part of
      Turkey. Water quality parameters were sampled from 1997 through 2001 for each
      year at five sites (three for Galyan, two for Degirmendere) along 29 and 42 km
      gradients, respectively covering all seasons. Surface water was collected from
      the sites and analyzed for temperature, total alkaline (MAAL), total dissolved
      solids (TDS), dissolved oxygen (DO), pH, conductivity (EC), nitrate (NO3),
      nitrite (NO2), total hardness (TH), phenolphthalein alkalinities (PAL) and
      organic matter (PV). Seasonal changes of water quality were analyzed
      statistically for both Rivers and evaluated according to the TS 266, EU and WHO
      standards. The analysis of variance results showed that Ca, Mg, MAL, NO3, pH, TDS
      and TH parameters of the Degirmendere River and Ca, DO, EC, MAL, NO3, pH and TH
      parameters of the Galyan River showed seasonal differences (p<0.05). The maximum
      values of the water pollution parameters for the two Rivers were below the
      threshold values throughout the study period. When both Rivers were compared, the
      mean values of the pollution parameters of the Degirmendere River were higher
      than those of the Galyan River and very close the limits. The results indicate
      that both Rivers can be used for the production of potable water during all
      seasons but only with an advanced treatment in the Degirmendere and a moderate
      treatment in the Galyan River, and for indirect and non-contact recreational
      activities.

PMID- 15248657
TI  - In vitro effects of metal ions on lipid peroxidation induced by alcohol in mice
      liver homogenate.
AB  - The study is aimed to estimate the effect of different heavy metals such as Hg2+,
      Cd2+, Mn2+, Cr3+, Ni2+, Se2O3(2-), As2O3 water solution and combined effects of
      Hg2+, Mn2+, Cr3+ on lipid peroxidation in mice liver homogenate in vitro. Lipid
      peroxidation was determined as thiobarbituric acid-reacting materials (TBA). We
      select five different concentrations of selected ions for experiments.
      Correlations used to identify the concentration of ions associated with lipid
      peroxidation. The rate of lipid peroxide formation in mice liver homogenate
      increased with the gradual addition of alcohol. When alcohol dose was up to 0.5
      ml, the rate of lipid peroxide formation was greatest. At tested concentrations,
      the effects of metal ions on lipid peroxidation induced by alcohol were
      classified into three groups, and are as follows: (1) simulative, Hg2+. (2)
      inhibitory, Mn2+, Cr3+, Ni2+, Se2O3(2-). (3) ambiguous, Cd2+, As2O3 water
      solution. When Hg2+, Mn2+ and Cr3+ were added to the mice liver homogenate with
      alcohol at the same time, Hg2+, Mn2+ were the main agents for the rate of alcohol
      induced lipid peroxidation. The simulative effect of Hg2+ on lipid peroxidation
      induced by alcohol indicate that alcohol-drinkers will have further health risk
      when they are exposed in polluted regions than others, and Mn2+, Cr3+, Ni2+,
      Se2O3(2-) may act as free radical scavengers and preventive remedy for alcoholism
      in part. Furthermore, analysis of combined effect of Hg2+Mn2+ and Cr3+ provide us
      a new way to estimate the combined effect of multi-materials.

PMID- 15248658
TI  - Landfill leachate-induced toxicity in mice.
AB  - Microbial, plant and studies in aquatic animals have shown that landfill leachate
      is toxic. However, more information about its effects in terrestrial animals is
      required. As a part of ongoing research into the toxic effects of landfill
      leachate in Nigeria, we evaluated the acute effects of raw and simulated
      leachates from Abadina, Orita-Aperin and Oworonsoki dump sites, all in Southwest
      Nigeria, in mice. Raw leachates were obtained directly from the dumps while the
      simulated leachates were obtained from the solid wastes in the laboratory by
      using the ASTM method. The samples were designated Abadina raw leachate (ARL),
      Orita-Aperin raw leachate (OARL) and Oworonsoki raw leachate (OWRL); and Abadina
      simulated leachate (ASL), Orita-Aperin simulated leachate (OASL) and Oworonsoki
      simulated leachate (OWSL). Their physico-chemical properties were determined in
      accordance with standard analytical methods. Young male mice (12-15 wk) weighing
      24-31 g were exposed to 1%, 5%, 10%, 25%, 50% and 100% concentrations of each
      test samples for 5 consecutive days and were observed for a period of 96 h for
      toxic response. Mortality recorded at different times for each sample at the
      various concentrations was mostly within the last 48 h of the exposure period.
      The LC50 obtained are 100% for both ARL and OARL, and 50% for OWRL; and 83.50%
      and 50% for ASL and OWSL, respectively. It was indeterminate for OASL. Apart from
      this, other toxic effects like weight loss, sluggishness, loss of hair and
      reduced food intake were observed. The investigated samples were ranked as OWRL >
      OWSL > ASL > OARL > ARL > OASL. The observed effects were due to the toxic
      constituents present in the leachate samples. This suggests that the mixtures
      have the potential to cause harmful effect to public health and our environment
      through seepage into ground or surface water.

PMID- 15248659
TI  - The effects of compost prepared from waste material of banana plants on the
      nutrient contents of banana leaves.
AB  - In this study, the possible utilization of removed shoots and plant parts of
      banana as compost after fruit harvest were investigated. Three doses (15-30-45 kg
      plan(-1)) of the compost prepared from the clone of Dwarf Cavendish banana were
      compared with Farmyard manure (50 kg plant(-1), Mineral fertilizers (180 g N +
      150 g P + 335 g K plant(-1)) and Farmyard manure + Mineral fertilizers (25 kg FM
      + 180 g N + 150 g P + 335 g K plant(-1)) which determined positive effects on the
      nutrient contents of banana leaves. The banana plants were grown under a heated
      glasshouse and in a soil with physical and chemical properties suitable for
      banana growing. The contents of N, P, K and Mg in compost and in farmyard manure
      were found to be similar. Nitrogen, phosphorus and potassium contents of leaves
      in all applications except control, and Ca, Mg, Fe, Zn, Mn, Cu contents in all
      applications were determined between optimum levels of reference values. There
      were positive correlations among some nutrient contents of leaves, growth, yield
      and fruit quality characteristics. Farmyard manure, Farmyard manure + Mineral
      fertilizers and 45 kg plant(-1) of compost increased the nutrient contents of
      banana leaves. According to obtained results, 45 kg plant(-1) of compost was
      determined more suitable in terms of economical production and organic farming
      than the other fertiliser types.

PMID- 15248660
TI  - Effect of fenvalerate technical grade on acetyl cholinesterase activity in Indian
      bullfrog Haplobatrachus tigerinus (Daudin).
AB  - Indian bullfrog Haplobatrachus tigerinus (Daudin) was exposed to sublethal dose
      (1/3 of LC50 I.E. 1.166 mg/kg) of fenvalerate technical grade and the effect was
      studied on the specific activity of acetyl cholinesterase in the different
      tissues of frog viz., brain, muscle, liver, kidney and testis at different time
      periods viz., 3,6, 12, 24, 48 and 72 hours. The inhibition of specific activity
      of acetyl cholinesterase was in the order of kidney > brain > muscle > liver >
      testis. A significant inhibition was noticed in kidney at 12 hours (-64.33%) and
      no effect was noticed at 3 hours in testis (+0.67%). The AChE activity was
      inhibited in first three hours of administration of fenvalerate in all the tissue
      tested. The inhibition continued upto 6 hours or 2 hours in different tissue but
      the recovery was started by 24 hours and almost completed by 72 hours.

PMID- 15248661
TI  - Effect of sodium metabisulphite on germination, growth and yield of Vigna
      sinensis, Savi.
AB  - In the present study, the impact of sodium metabisulphite (Na2S2O5), a food
      preservative, on seed germination, growth and yield of Vigna sinensis, Savi has
      been evaluated. Observations clearly reveal the deleterious effect of Na2S2O5 on
      germination, stomatal development, stomatal index, chlorophyll content and yield.
      The shoot length exhibited a steady rise in length, while the biomass showed a
      gradual decrease with the increasing doses of Na2S2O5.

PMID- 15248662
TI  - Differential effect of cadmium and mercury on growth and metabolism of Solanum
      melongena L. seedlings.
AB  - The present investigation reports the results of the effect of cadmium and
      mercury individually on seed germination, seedling growth, number of lateral
      roots, fresh and dry weights and seedling metabolism in Solanum melongena. Effect
      of different concentrations of these two heavy metals (Cadmium--50, 100, 300,
      500, 700, 1000, 3000, 5000, 7000 and 9000 ppm and Mercury--5, 10, 15, 20, 25, 30,
      35, 40, 45 and 50 ppm) and durations for 6, 12 and 24 h were employed for all
      seedling parameters of brinjal. Both Cd and Hg showed drastic effects at high
      concentrations and longer duration with regard to seedling growth and metabolism.

PMID- 15248663
TI  - Heavy metal toxicity on dehydrogenase activity on rhizospheric soil of
      ectomycorrhizal pine seedlings in field condition.
AB  - The present investigation was carried out to study the toxicity of heavy metals
      (Zn, Cd, Cu, Ni, Pb and Al) on the dehydrogenase activity of ectomycorrhizal
      (Suillus leutus, Scleroderma aurantium, Cenococcum graniforme and Boletus spp.)
      and non-mycorrhizal rhizospheric soil of pine seedlings. The treatment of heavy
      metals adversely affected the dehydrogenase activity. Inoculation of mixed
      ectomycorrhizal fungi harbored increased activity of dehydrogenase. It was
      observed that in absence of ectomycorrhizae, heavy metals drastically reduced the
      enzyme activity at higher concentration of metals.

PMID- 15248664
TI  - Dental fluorosis in bovine of Nayagarh district of Orissa.
AB  - Chronic fluoride toxicity in the form of dental fluorosis was observed in cattle
      from nine (9) villages under two (2) blocks of Nayagarh district of Orissa. Out
      of 1117 cattle, 221 (18.09%) showed the signs of dental fluorosis. In all
      affected villages, the prevalence of dental fluorosis in calves (< 1 year age)
      was greater than adults. There was significant difference in prevalence in
      respect to age. The commonly observed signs of dental fluorosis were brown
      discoloration, mottling, attrition or uneven wearing of teeth with or without
      pitting. None of the affected animals showed characteristic signs of
      osteofluorosis. The mean serum and urine fluoride concentration of affected
      animals were significantly (P < 0.05) higher than those of control animals.
      Fluoride levels (mean) of ground water and surface water in two blocks were 1.30
      +/- 0.16 ppm, 0. 66 +/- 0.08 ppm and 1.12 +/- 0.19 ppm, 0. 48 +/- 0.05 ppm
      respectively. The fluoride content of grass samples of affected and control (non
      endemic) area was comparable. There was a highly positive correlation (r = +
      0.664) between prevalence of dental fluorosis and fluoride content of ground
      water. It was concluded that fluoride intake through the water especially ground
      water contributed to the development of fluorosis in cattle.

PMID- 15248665
TI  - Diversity of ground arthropod community at organic and chemically intensive tea
      plantation of Darjeeling terai.
AB  - Tea in Darjeeling foothills and terai are grown conventionally, with application
      of chemical fertilizers and pesticides, as well as organically without these
      inputs. Ground level arthropod community was collected from the above two types
      of tea plots using pitfall traps. Catches from these environments showed
      variation in the arthropod faunal structure with numerically and taxonomically
      greater abundance in the organic than that of the conventional plot. Coleopterans
      were more diverse with largest number of families and Recognizable Taxonomic
      Units (or morphospecies) in the organic tea plot. The diversity and similarity
      indices for coleopterans were comparable, in organic and conventional tea plots
      at species and family levels. The close relationship of the indices suggested
      that diversity study at family level could be used as surrogate for species level
      diversity; thus alleviating the laborious and expertise job of taxonomic
      identification of arthropod species. Faunal diversity study at ground level gave
      the clue that soil of the organic plantation was healthier than that of the
      conventional tea plot.

PMID- 15248666
TI  - Studies on Merops orientalis Latham 1801 with special reference to its population
      in Mayiladuthurai, Tamil Nadu.
AB  - Role of habitat-structure and climatic factors in the population dynamics of the
      small green bee-eater Merops orientalis was evaluated in three habitats viz.,
      agricultural lands, river banks and human habitations during 1991-1993. The river
      banks supported relatively high population of bee-eaters (157/Km2) followed by
      the agricultural lands (101/Km2) and human habitations (58/Km2). Bee-eater
      populations showed year-wise variations in river banks and human habitations
      having high values during 1992 (123/Km2) and 1993 (43/Km2) respectively.
      Agricultural lands showed a significantly low mean density in 1991 than other
      years. Seasonal variations in the bee-eater densities among the habitats were
      also recorded. Vegetation structure, food (insects) availability, climatic
      conditions and human disturbance were the casual factors for variations in bee
      eater populations.

PMID- 15248667
TI  - Comparative account of certain enzymes in the serum of homo-iothermal vertebrates
      subjected to production of myocardial infarction by isoproterenol hydrochloride.
AB  - Myocardial infarction was produced by subcutaneous administration of
      isoproterenol hydrochloride (85 mg/kg b.w. for two consecutive days). The
      myocardial damage was proved by observing increase in the activity of SGOT and
      SGPT in serum whereas AChE activity was inhibited by increasing Km, without
      affecting Vmax. The inhibition of AChE and inhibitory kinetic may be useful in
      the diagnosis and management of salvage of myocardium.

PMID- 15248668
TI  - Chemical components of heartwood and sapwood of common Yew (Taxus baccata L.).
AB  - Cell-wall components and solubility characteristics of the heartwood and sapwood
      of Taxus baccata L. were determined by methods of wood analysis and the
      differences between heartwood and sapwood were established. When we observe the
      data obtained, it is seen that the amount of extractive material found in the
      heartwood is substantially higher than the sapwood. The extractive material in
      Taxus baccata L. is originated from the hidden epithelial cells surrounded by
      resin canals.

PMID- 15248669
TI  - Effect of nicotine (plant extract) on sex-ratio of Drosophila melanogaster
      (Meigen).
AB  - Experiments were conducted by using nicotine (plant extract) for its toxic
      effects on Drosophila melanogaster, LC50 estimated is 2.9552 microl/100 ml.
      Studies revealed that nicotine affects adult emergence of males and females (sex
      ratio) of mutant form (Yellow) of Drosophila melanogaster.

PMID- 15248670
TI  - HLA system and cancer.

PMID- 15248671
TI  - Prognostic significance of HLA-DR antigen in dysplasia, carcinoma in situ and
      invasive carcinoma of the gallbladder.
AB  - OBJECTIVE: Prognosis of gallbladder carcinoma is poor. The two most important
      factors having the greatest effect on survival are pathologic stage of disease
      and histologic grade of the tumour. Our study points towards the value of HLA-DR
      antigen in the prognosis of gallbladder carcinoma. DESIGN: Thirty one cases of
      dysplasia of the gallbladder, 12 cases of carcinoma in situ, and 39 cases of
      invasive carcinoma for the detection of HLA-DR monoclonal antigen were studied. T
      helper (TH) marker (CD4) in the tumour stroma of the relevant cases was also
      studied, given that it is now known that the dependence of immune responsiveness
      on the class II antigens reflects the central role of these molecules in
      presenting antigen to TH cells. SETTING: Pathology Departments of Drama General
      Hospital and Ippokration Hospital of Salonica in twelve years period (1990-2002).
      RESULTS: HLA-DR was expressed in 20 of 31 dysplasias (64.5%), four of 12 in situ
      (33.3%), and in 10 of 39 invasive carcinomas (25.6%). CD4 was expressed in nine
      of 31, dysplasias (29%), five of 12 in situ (42%), and in 26 of 39 invasive
      carcincomas (67%). CONCLUSIONS: The results showed decreased expression of HLA-DR
      and increased expression of CD4 as the lesion progressed to malignancy. The
      aberrant expression of HLA-DR by epithelial cells of dysplasias, of carcinomas in
      situ and of invasive carcinomas agrees with the hypothesis of the dysplasia
      carcinoma in situ sequence as the usual route for the development of invasive
      carcinoma. The immune attract mechanism by low HLA-DR signalling seems to be of
      minor importance in the malignant and metastatic potential of the gallbladder,
      epithelial tumours.

PMID- 15248672
TI  - Determination of aetiology of superficial enlarged lymph nodes using fine needle
      aspiration cytology.
AB  - OBJECTIVE: To asses the causes and patterns of enlarged superficial lymph nodes.
      DESIGN: Cross sectional survey. SETTING: Jimma Teaching Hospital, Pathology
      Department, Jimma University, Southwest Ethiopia for a study conducted between
      September 1999 and August 2001. PARTICIPANTS: Eight hundred and eight patients
      presenting with enlarged superficial lymph nodes in cervical, axillary, inguinal
      etc. regions were included (456 males and 352 females) whereas non lymph node
      samples and deep-seated lymphoid lesions were excluded from the study. MAIN
      OUTCOME MEASURES: Fine needle aspiration cytology (FNAC) technique and Wright's
      staining procedure were utilized to diagnose the causes of enlarged lymph nodes.
      RESULTS: Of the 1693 patients attended to at the cytologic diagnostic service,
      808(47.7%) had lymph node disorders with benign and malignant causes of lymph
      node enlargements comprising of 93.2% and 6.8% respectively. The most frequent
      cause of benign enlargement was tuberculous lymph adenities (66.3%), followed by
      reactive lymph node hyperplasia (19.2%). Among malignant ones, non-Hodgkin's
      lymphomas (2.7%) and metastatic carcinomas (2.2%) were most frequently diagnosed.
      The cervical region was the most frequent site for enlarged lymph node disorders
      accounting for more than three quarters of all cases. CONCLUSION: This study
      revealed a huge burden of benign lymph node enlargements in general, and
      tuberculous lymph adenities in particular. The latter was responsible for about
      two-third of lymph node enlargements in South Western parts of this country. It
      is recommended that health providers undertake intensive public health education
      and screening activities in order to help salvage our community from these
      potentially preventable and treatable causes of enlarged lymph node disorders.

PMID- 15248673
TI  - Lupus anticoagulants: pathophysiology, clinical and laboratory associations: a
      review.
AB  - OBJECTIVES: To put together salient clinical and laboratory manifestations and
      also to highlight the pathophysiology and principles of management of lupus
      anticoagulants syndrome. DATA SOURCES: Publications, original and review
      articles, conference abstracts searched mainly on PubMed indexed for Medline.
      DATA EXTRACTION: A systematic review to identify studies relating to lupus
      anticoagulants, clinical, laboratory, pathophysiology and management. Only data
      relevant to the objectives of the review were extracted. DATA SYNTHESIS: A
      detailed qualitative assessment was undertaken given the heterogeneity of study
      types making it not appropriate to pool results across studies. CONCLUSION: It is
      demonstrated that lupus anticoagulants (LA) are associated with thrombotic
      events, recurrent foetal loss and female infertility and also occasionally with
      bleeding due to thrombocytopenia or hypoprothrombinaemia LA interferes with
      phospholipid dependent laboratory test of coagulation and the test are not
      corrected by addition of normal plasma. False positive antiphospholipid antibody
      test is noted frequently in patients. LA has been detected in all races and
      geographical regions in the world. The treatment involves use of corticosteroids,
      anticoagulants, immunoglobulins and occasionally cytotoxic drugs and
      plasmapheresis long-term prophylaxis and follow up of patients with IgG
      antiphospholipid antibodies are recommended. Screening for LA considered in
      patients with unexplained; thrombotic events, foetal loss and bleeding.

PMID- 15248674
TI  - Community chloroquine distribution for malaria control in Bushenyi district of
      Uganda.
AB  - OBJECTIVE: To document successful community chloroquine distribution for malaria
      control in Bushenyi district, southwestern Uganda. DESIGN: A cross sectional
      survey immediately after a four-month community chloroquine distribution
      exercise. One hundred sixty seven distributors in 140 out of 166 parishes in
      Bushenyi district did the chloroquine distribution during the 2001 malaria
      epidemic. PARTICIPANTS: A cluster random sample of 215 heads of households or
      their spouses were interviewed using a pre-tested questionnaire. MAIN OUTCOME
      MEASURES: Socio-demographic characteristics, malaria/fever morbidity, health
      seeking behaviour in the previous four months, knowledge about chloroquine
      distribution, opinions about the chloroquine distribution exercise and whether
      the household had used the service of the chloroquine distributors. RESULTS:
      Thirty per cent of the people surveyed had suffered from malaria in the previous
      four months. Seventy per cent of the households were aware of the chloroquine
      distribution and 56% of the patients who had malaria in the previous four months
      accessed the services of chloroquine distributors. People who were aware of
      chloroquine distributors were less likely to use services where a fee is levied.
      The total cost of chloroquine distribution was about 20,000 United States
      dollars. CONCLUSIONS: Community chloroquine distribution can increase access to
      treatment and can be done in a short time at an affordable cost.

PMID- 15248675
TI  - Partial characterisation of a trypanosome-lysing factor from the midgut of the
      desert locust, Schistocerca gregaria.
AB  - OBJECTIVE: Screening and biochemical characterisation of trypanosome-lysing
      factor (trypanolysin) from non-vector insect, Schistocerca gregaria. DESIGN:
      Laboratory based experiment. SETTING: Department of Biochemistry, University of
      Nairobi. RESULTS: Lysis of isolated trypanosomes was demonstrated with midgut
      homogenates of natural vector Glossina morsitans centralis as well in non-vector
      insects. The highest trypanolytic activity was observed in midgut homogenate of
      the desert locust. Schistocerca gregaria followed by the cockroach, Periplaneta
      americana (L). Further studies on the S. gregaria trypanolytic factor showed its
      proteinaceous nature due to its sensitivity to temperatures above 40 degrees C
      and to proteases. Additionally, the factor showed lectin-like properties since
      the activity was blocked by D-glucosamine. CONCLUSION: The trypanolytic factor
      has the potential of being used to modulate tsetse fly vectorial capacity.

PMID- 15248676
TI  - Critical appraisal of the law enforcement in abortion care in Ethiopia.
AB  - OBJECTIVE: To illustrate the disparity in the law enforcement in abortion care
      and the widely reported induced abortion rates. DESIGN: A descriptive study.
      SETTING: The computer-entered data from the Federal Democratic Republic of
      Ethiopia Police Information and Documentation Center. MATERIALS AND METHODS: Two
      hundred and sixteen case files handled by the police in the last two years. The
      data of 326 subjects accused of alleged abortion related legal wrong doings were
      analysed for age, marital status, educational level, occupation and the due
      process in the court of law. The magnitude of induced abortions is reviewed from
      the available institutional based studies. RESULTS: The majority of aborting
      mothers, the service providers and their accomplices are found to be young,
      unmarried, poorly educated and of low socio-economic profile. The files that are
      under investigation and pending court rulings are remarkably high. The published
      incidence of induced abortion ratio of 318 per 1,000 live births is
      disproportionately greater than those that actually come under the attention of
      the law. CONCLUSION: The 1957 law is not officially repealed and its restrictive
      nature is not influencing the prevalence of illicitly induced abortions since the
      legal instruments are not fully operational. This is the consequence of fewer
      complaints advanced to the police and/or lack of obligatory reporting system of
      the events by the service delivery points.

PMID- 15248677
TI  - Anal sphincter reconstruction for incontinence due to non-obstetric sphincter
      damage.
AB  - OBJECTIVE: To assess the outcome after anal sphincteroplasty in patients with
      anal incontinence following non-obstetric anal sphincter damage. DESIGN: A
      prospective study carried out in an urban teaching hospital over five years (1994
      1998). PATIENTS AND METHODS: Fourteen patients, median age of 30 years, all
      undergoing anal sphincter reconstruction. The procedure was performed under
      general or regional anaesthesia. Operative management was (i) excision of the
      scar tissue and apposition of the cut ends of the sphincter or (ii) a reefing
      technique. RESULTS: Sphincter damage was as a result of trauma in nine cases,
      haemorrhoidectomy in two cases, sepsis in two and failed recto-vaginal fistula
      repair in one case. In six patients with traumatic sphincter damage a colostomy
      was performed at original operation. The other eight presented with incontinence,
      four of whom required a diverting colostomy prior to repair. The median delay
      between sphincter injury and repair was six months (range 4-120). The posterior
      approach was used in eight patients, an anterior approach in five and both
      approaches in one. Non-absorbable suture material was used in six and absorbable
      material was used in eight patients. Twelve of the 14 patients had scar tissue at
      the site of damage requiring excision. Two post-haemorrhoidectomy patients
      underwent the reefing technique. Eleven patients (79%) were completely continent
      after initial repair. Two required further repair resulting in complete
      continence. One patient remained with mild incontinence. CONCLUSION: Anal
      sphincter reconstruction for non-obstetric anal incontinence produced good short
      term results.

PMID- 15248678
TI  - Planned vaginal delivery versus Caesarean section for breech presentation in Ile
      Ife, Nigeria.
AB  - BACKGROUND: The optimum mode of breech delivery remains a matter of controversy
      among obstetricians worldwide. OBJECTIVE: To determine whether term breech babies
      born by planned vaginal delivery are at higher risk of neonatal mortality and
      morbidity than those born by planned caesarean delivery. DESIGN: A hospital based
      non-experimental comparison of outcome of breech delivery. SETTING: Ife State
      Hospitals Complex, Ile-Ife. SUBJECTS: Two hundred and fourty four singleton
      breech deliveries occurring at term. MAIN OUTCOME MEASURES: They include low 5
      minute Apgar score, birth trauma, maternal and perinatal morbidity and mortality.
      RESULTS: The perinatal mortality was not significantly different in both groups:
      OR 2.7 (95% C.I. 0.3-26.8). The low 5-minute Apgar scores were higher in the
      planned vaginal delivery OR 9.0 (95% C.I. 1-73.4), but the traumatic morbidity
      was not (OR 1.8, 95% C.I. 0.2-20.1). Maternal morbidity occurred more in the
      planned Caesarean delivery group OR 0.4 (95% C.I. 0.2-0.9). CONCLUSION: Given
      appropriate selection criteria and management protocol, the outcome from elective
      caesarean section might not be better than from planned vaginal delivery.

PMID- 15248679
TI  - Functional disturbances in children after ano-rectal surgery.
AB  - OBJECTIVE: To determine the prevalence, clinical presentation, highlight
      management methods and outcome of treatment modalities in children who presented
      at the University of Calabar Teaching Hospital, Calabar with complications from
      previous ano-rectal operations. DESIGN: Prospective study of ano-rectal
      complications from previous ano-rectal surgery in children over a seven year
      period. SETTING: University of Calabar Teaching Hospital, Calabar, a referral and
      teaching hospital. SUBJECTS: All cases of complications from previous ano-rectal
      surgery in children that presented at the paediatric surgical clinic of the
      University of Calabar Teaching Hospital (UCTH), Calabar, between January 1994 and
      December 2000. INTERVENTION: Conservative measures were commenced in all cases
      and involved diet manipulation, enema and physiotherapeutic training. RESULTS:
      The age of maximum presentation was within the 6-10 year age bracket. The main
      presenting complain was faecal soilage and poor bowel habit. The children notably
      presented late and was as a result of societal embarrassment at school. Before
      then the child was within the home environment hence parents may not bother.
      Complications from anal agenesis operation accounted for the majority of patients
      45(54%) while aganglionic megacolon accounted for 39 patients (46%). Treatment in
      all cases started conservatively with diet manipulation, cleansing enema and
      physiotherapeutic training. However, with non improvement in faecal soilage, a
      simple repair involving a narrowing at the ano-rectal junction was carried out.
      In a follow-up period of between 6-12 months, 45 children had satisfactory
      clinical status while in 27 children their general conditions had improved.
      CONCLUSION: Perseverance and tolerance from the surgeon, the parents and the
      patient-child is required in these conditions. The late presentation may have
      helped as the fibres of the external sphincter muscles perhaps have further
      developed. At this period the child is also psychologically aware of his problem.

PMID- 15248680
TI  - Eagle-Barrett syndrome: occurrence and outcomes.
AB  - OBJECTIVE: To examine the occurence and outcomes of African babies born with
      features of Eagle-Barret syndrome at a tertiary health centre. DESIGN: Case
      series. SETTING: University Teaching Hospital, Yaounde, Cameroon. SUBJECTS:
      Patients were identified through a retrospective review of obstetric records of
      mothers admitted at the centre within the period 1984 to 1996 inclusive. A total
      of eleven cases were identified over a period of thirteen years. RESULTS: The
      most prominent associated defects consisted of clubfoot, pulmonary hypoplasia,
      Potter's facies, imperforate anus and arthrogryposis. None of our patients
      survived the perinatal period. CONCLUSION: Our study indicates the need for the
      establishment of a prenatal and cytogenetic infrastructure in Cameroon to enhance
      early detection of congenital malformation and chromosomal aberrations. In the
      meantime, early detection of foetuses with Eagle-Barret syndrome using ultrasound
      could facilitate timely institutions of antenatal management options and lead to
      favourable birth outcomes of affected babies.

PMID- 15248681
TI  - Substance use among children and young persons appearing in the Nairobi Juvenile
      Court, Kenya.
AB  - OBJECTIVE: To estimate the prevalence and pattern of substance use among children
      and young persons appearing in the Nairobi Juvenile Court, Kenya. DESIGN: A point
      prevalence survey. SETTING: The Nairobi Juvenile Court, Kenya. SUBJECTS: Ninety
      (sixty four males and twenty six females) children and young persons aged 8 to 18
      years classified as criminal offenders, group I (60) and those for protection and
      discipline, group II (30), were selected. METHOD: Socio-demographic and substance
      use questionnaires were administered to the subject. International classification
      of diseases, 10th Edition (ICD-10) diagnostic criteria were used. RESULTS: Crude
      rate for substance use in this study was found to be 39 out of the total sample
      of 90(43.3%), children and young persons. Of these thirty nine, 33 (85.8%) were
      males and six(14.2%) were females. Twenty nine (32.2%) used nicotine, 19(21.1%)
      used volatile hydrocarbons, 8(8.9%) used cannabis six (6.7%) used alcohol, five
      (5.6%) used khat and three (3.3%) used sedatives. Multiple substance use was also
      evident. CONCLUSION: This study has shown a high presence of substance use in
      children and young persons appearing in the Nairobi Juvenile Court.

PMID- 15248682
TI  - Small intestinal obstruction due to Bilharzioma: case report.
AB  - Schistosomiasis in endemic areas affects all age groups and present with various
      clinical manifestations. Small intestinal obstruction as a complication of
      Schistosomiasis was not described in the literature. This is a report of a 10
      year old child from an endemic area with an unusual presentation of subacute
      small intestinal obstruction. Description of the pathological changes in the
      intestines following infestation with Schistosomiasis and brief presentation of
      the control modality in this endemic area are given.

PMID- 15248683
TI  - Leukaemia cutis in a patient with acute myelogenous leukaemia: case report.
AB  - Leukaemia cutis is a specific lesion of leukaemia in which there is leukaemic
      cell deposit in the skin. There are few reports of this condition in our
      environment. Several mechanisms have been postulated for the pathogenesis of the
      disease. One of which is the tissue selective homing of a unique sub-population
      of malignant clone of cells. The presence of leukaemia cutis does not seem to
      worsen the prognosis as the acute myeloid leukaemia is an equally lethal disease.
      The fatality of the disease is compounded by the unavailability of the right
      regimen in our patient. This paper documents a case of leukaemia cutis in a
      patient initially diagnosed to have AML who developed skin lesion in remission. A
      skin biopsy was found helpful in diagnosing the first sign of relapse in a
      patient in haematological remission.

PMID- 15248684
TI  - Dendrimer-activated surfaces for high density and high activity protein chip
      applications.
AB  - Highly functional Si and glass surfaces for protein immobilization have been
      prepared by a facile activation of native surface silanol groups.
      Poly(propyleneimine) dendrimers of generations 1-5 were immobilized onto the
      surface using a facile room-temperature coupling procedure that involved
      activation of native silanol groups of glass using 1,1'-carbonyldiimidazole under
      anhydrous conditions. The dendrimer-coated surfaces were used to immobilize
      proteins and were characterized with respect to surface loading and activity. A
      number of different chemical, physical, and biochemical techniques including
      contact angle measurement, ellipsometry, and fluorescence microscopy were used to
      characterize the resulting surfaces. Increasing the dendrimer generation past G-3
      led to increased surface amine content, immobilized protein concentration, and
      the activity of immobilized alkaline phosphatase (used as a test system). Very
      high activity of the immobilized proteins in the case of higher generation (G-4
      and G-5) dendrimers led us to conclude that such an approach has true potential
      for creating highly functional surfaces for protein chip applications.

PMID- 15248685
TI  - Single nanocrystal arrays on patterned poly(ethylene glycol) copolymer
      microstructures using selective wetting and drying.
AB  - Single nanocrystal arrays were fabricated on sub-microwells of poly(ethylene
      glycol) (PEG) copolymer using selective wetting on the hydrophilic regions of the
      exposed substrate surface and subsequent drying. Templates were produced by
      molding a thin film of a PEG-based random copolymer on hydrophilic substrates
      such as glass or silicon dioxide. The polymeric microstructures provide a
      topographical barrier around the well, which makes it possible to create
      nanocrystal arrays with controlled geometrical features. The size of the
      nanocrystal was found to decrease with decreasing well size and also decrease
      with decreasing topological height. A simple empirical equation was derived to
      predict the size of the crystal as a function of the pattern size and height,
      which is in good agreement with the experimental data.

PMID- 15248686
TI  - Generic approach for dispersing single-walled carbon nanotubes: the strength of a
      weak interaction.
AB  - A generic noncovalent approach for dispersing high concentrations of individual
      single-walled carbon nanotubes (SWNT) in organic as well as aqueous solutions of
      synthetic block copolymers is presented. It is suggested that a weak, long-ranged
      entropic repulsion among polymer-decorated tubes acts as a barrier that prevents
      the tubes from approaching the attractive part of the intertube potential. The
      method opens a new route for utilization of block copolymers as compatibilizers
      for SWNT, improving the incorporation of de-agglomerated SWNT into target
      polymeric matrixes.

PMID- 15248687
TI  - Synthesis of dumbbell-shaped Au-Ag core-shell nanorods by seed-mediated growth
      under alkaline conditions.
AB  - We report a simple synthesis of Au-Ag core-shell nanorods (NRs) under alkaline
      conditions (pH 8.0-10.0) from silver and ascorbate ions using gold nanorods
      (GNRs) as the seeds. The silver ions that are reduced by the ascorbate ions
      become deposited on the surfaces of the GNRs to form differently dumbbell-shaped
      Au-Ag core-shell NRs and nanoparticles, depending on the pH and the concentration
      of silver ions. The longitudinal plasmon absorbance bands of the Au-Ag core-shell
      NRs are stronger and appear at shorter wavelengths than those for the original
      GNRs. We confirmed the formation of Au-Ag core-shell NRs by both energy
      dispersive X-ray spectrometry and inductively coupled plasma mass spectrometry
      measurements, which indicate that the 109Ag/197Au ratios are 0.046, 0.085, and
      0.097 at pH 8.0, 9.0, and 10.0, respectively. The transmission electron
      microscopy measurements show that the Au-Ag core-shell NRs are monodispersed
      (>90%).

PMID- 15248688
TI  - Adsorbed and spread beta-casein monolayers at oil-water interfaces.
AB  - A previous study (Langmuir 2003, 19, 8436) used a Langmuir type pendant drop film
      balance to form beta-casein monolayers at the air-water interface. The present
      paper reports the application of that technique to the formation of protein
      monolayers at liquid interfaces. This technique allows a direct comparison
      between spread and adsorbed beta-casein interfacial behaviors that is presented
      in terms of their pi-A isotherms and static elasticity moduli. Pi-A isotherms of
      adsorbed and spread protein have been compared and found to be fairly similar in
      shape, stability, and also hysteresis phenomena. Examination of the elasticity
      moduli of both layers shows a similar analogy although slight differences arise
      and are interpreted in terms of the protein unfolding extent attained by both
      procedures at the oil interface.

PMID- 15248689
TI  - Computer simulation of the microstructure of a nanoparticle monolayer formed
      under interfacial compression.
AB  - The uniaxial compression of a monolayer of nanosized monodisperse spherical
      particles adsorbed at a planar interface is simulated using the Brownian dynamics
      technique. Initially, the particles spread at the interface form crystalline
      loosely interconnected clusters. As the interface is compressed, the gaps between
      the clusters are removed and a close-packed monolayer is formed. At this stage,
      the structure of the interface consists of two-dimensional crystalline grains
      separated by defect boundaries. Further interfacial compression induces
      desorption of nanoparticles at these boundaries and creates striplike patterns of
      a secondary adsorbed layer. The structural features observed show remarkable
      agreement with recent experimental studies of the compression of gold
      nanoparticles in a Langmuir trough.

PMID- 15248690
TI  - Factors affecting responsivity of unilamellar liposomes to 20 kHz ultrasound.
AB  - Ultrasound is commonly used in the preparation of unilamellar liposome
      dispersions and is often considered for cell membrane disruption for drug
      delivery or DNA transfection applications. To better understand the physical and
      chemical properties of lipid membranes that render them susceptible to ultrasonic
      permeabilization, the roles of temperature, lipid composition (cholesterol and
      PEG-lipid content), and liposome size have been studied. The results of these
      studies suggest that lipid packing is very important to ultrasound
      responsiveness; surprisingly, cohesive energy and tensile strength are not. Taken
      together, the experimental results implicate a defect-mediated permeabilization
      mechanism, rather than pore formation or membrane tearing. The implications of
      this work for drug release from liposomes and ultrasound-mediated DNA
      transfection are discussed.

PMID- 15248691
TI  - A nucleophilic substitution reaction performed in different types of self
      assembly structures.
AB  - A nucleophilic substitution reaction between 4-tert-butylbenzyl bromide and
      potassium iodide has been performed in oil-in-water microemulsions based on
      various C12Em surfactants, i.e., dodecyl ethoxylate with m number of oxyethylene
      units. The reaction kinetics was compared with the kinetics of reactions
      performed in other self-assembly structures based on very similar surfactants and
      in homogeneous liquids. The reaction was fastest in the micellar system,
      intermediate in rate in the microemulsions, and most sluggish in the liquid
      crystalline phase. Reaction in a Winsor I system, i.e., a two-phase system
      comprising an oil-in-water microemulsion in equilibrium with excess oil, was
      equally fast as reaction in a one-phase microemulsion. The reactions in
      microemulsion were surprisingly fast compared to reaction in homogeneous, protic
      liquids such as methanol and ethanol. The rate was independent of the
      microstructure of the microemulsion; however, the rate was very dependent on the
      type of surfactant used. When the C12Em surfactant was replaced by a sugar-based
      surfactant, octyl glucoside, the reaction was much more sluggish. The high
      reactivity in microemulsions based on C12Em surfactants is belived to be due to a
      favorable microenvironment in the reaction zone. The reaction is likely to occur
      within the surfactant palisade layer, where the water activity is relatively low
      and where the attacking species, the iodide ion, is poorly hydrated and, hence,
      more nucleophlic than in a protic solvent such as water or methanol. Sugar
      surfactants become more hydrated than alcohol ethoxylates and the lower
      reactivity in the microemulsion based on the sugar surfactant is probably due to
      a higher water activity in the reaction zone.

PMID- 15248692
TI  - Solubilization of n-alkylbenzenes in aggregates of sodium dodecyl sulfate and a
      cationic polymer of high charge density (II).
AB  - The solubilization property of the aggregate composed of sodium dodecyl sulfate
      (SDS) and a cationic polymer (polydiallyldimethylammonium chloride, PDADMAC) was
      investigated. From the binding isotherm, the increasing free SDS concentration
      (Cf) above the critical aggregation concentration (cac) was clearly confirmed and
      used to calculate the Gibbs free energy change of solubilization. The maximum
      additive concentration of the alkylbenzene solubilizates remained almost constant
      around their aqueous solubilities below the cac and then increased with
      increasing SDS concentration above the cac and with decreasing alkyl chain length
      of the solubilizates. Also, their solubility increased with increasing
      temperature over the concentration range of the surfactant examined. Because the
      monomeric DS- concentration in the aqueous phase (Cf) increased with the SDS
      concentration above the cac in the SDS/PDADMAC system, Cf was evaluated from the
      binding isotherm to calculate the change in the Gibbs energies of transfer of the
      solubilizates using the phase separation model. The Gibbs energy change for the
      solubilizates decreased with increasing temperature and increasing alkyl chain
      length. The decrease in the Gibbs energy per CH2 group (DeltaGCH2 degrees) was
      favored by an increase of temperature, and it was larger in magnitude than that
      for micelles of single-surfactant systems. From the values of DeltaH degrees and
      TDeltaS degrees, the solubilization of alkylbenzenes into SDS/PDADMAC was found
      to be entropy-driven.

PMID- 15248693
TI  - UV causes dramatic changes in aggregation with mixtures of photoactive and inert
      surfactants.
AB  - Aqueous mixtures of photosensitive and inert surfactants have been prepared;
      photoreactions and changes in aggregation after irradiation have been
      characterized. The photosensitive component was a stilbene-containing gemini
      photosurfactant (E-SGP), and the inert surfactants were either DTAB
      (dodecyltrimethylammonium bromide) or one of two different gemini surfactants, 12
      4-12 or 16-4-16 (butanediyl-1,4-bis(dodecyldimethylammonium bromide) or
      butanediyl-1,4-bis(hexadecyldimethylammonium bromide)). Small-angle neutron
      scattering (SANS) studies revealed that in general the initial nonirradiated
      mixed systems form vesicle-type aggregates (100-200 angstroms radius), in
      equilibrium with some smaller charged spheroidal or ellipsoidal micelles
      (approximately 20 angstroms radius). In all cases, UV irradiation resulted in
      disruption of these vesicles and the formation of charged micelles. 1H NMR showed
      that the main photoproduct is the cis, anti, cis dimer of E-SGP (ZEZ-DiSGP);
      hence, photochemically induced changes in the reactive SGP drive significant
      changes in the preferred aggregation structure. These results demonstrate the
      utility of photoactive surfactants in mixtures with inert analogues.

PMID- 15248694
TI  - Giant liposome microreactors for controlled production of calcium phosphate
      crystals.
AB  - Calcium phosphates are among the most important biominerals in living organisms,
      where they play both a mechanical and a calcium storage role. Their growth in
      vivo is under strong biological control, and this process occurs in closed
      spaces. Our aim in this paper is to describe a microreactor system able to
      control the mineralization process within closed spaces. To this aim we produce
      giant liposomes containing calcium ions as active ions in the mineralization
      process, spermine as an activator of crystal growth, and alkaline phosphatase as
      a catalyst to convert phosphate esters into phosphates. These phosphate esters
      are provided in the form of p-nitrophenyl phosphate outside of the liposomes. It
      is demonstrated that these amphiphilic molecules are able to diffuse through the
      lipidic container and to be subsequently hydrolyzed under enzymatic catalysis
      into active phosphate species which interact with the already available calcium
      and spermine to produce calcium phosphates only in the interior of the liposomes.
      This opens the route to control the calcium phosphate particle size in biomimetic
      systems.

PMID- 15248695
TI  - Controllable gelation of methylcellulose by a salt mixture.
AB  - The effects of a salt mixture consisting of a salt-out salt (NaCl) and a salt-in
      salt (NaI) on the sol-gel transition of methylcellulose (MC) in aqueous solution
      have been studied by means of micro differential scanning calorimetry and
      rheometry. The salt mixture was found to have a combined effect from the salt-out
      and salt-in salts in the mixture, and the salt effect was dependent on the water
      hydration abilities of the component ions and ion concentration. At a fixed total
      salt concentration, the sol-gel transition temperature nicely followed a rule of
      mixing: Tp = m1Tp1 + m2Tp2 where Tp, Tp1, and Tp2 are the gelation peak
      temperatures for the MC solutions with a salt mixture, NaCl, and NaI,
      respectively, and mi is the molar fraction of the salt component i in the salt
      mixture. The linear rule of mixing proved that the effects of NaCl and NaI on the
      sol-gel transition of MC are completely independent. In addition, the presence of
      a single salt or a salt mixture in a MC solution does not change the essential
      mechanism of MC gelation. Therefore, the sol-gel transition of MC can be simply
      controlled by a salt mixture consisting of a salt-out salt and a salt-in salt.
      The rheological results supported the micro thermal results excellently. But the
      gel strength of MC containing salts was influenced by both salt type and salt
      concentration.

PMID- 15248696
TI  - Electrodipping force acting on solid particles at a fluid interface.
AB  - We report experimental results which show that the interfacial deformation around
      glass particles (radius, 200-300 microm) at an oil-water (or air-water) interface
      is dominated by an electric force, rather than by gravity. It turns out that this
      force, called for brevity "electrodipping," is independent of the electrolyte
      concentration in the water phase. The force is greater for oil-water than for air
      water interfaces. Under our experimental conditions, it is due to charges at the
      particle-oil (instead of particle-water) boundary. The derived theoretical
      expressions, and the experiment, indicate that this electric force pushes the
      particles into water. To compute exactly the electric stresses, we solved
      numerically the electrostatic boundary problem, which reduces to a set of
      differential equations. Convenient analytical expressions are also derived. Both
      the experimental and the calculated meniscus profile, which are in excellent
      agreement, exhibit a logarithmic dependence at long distances. This gives rise to
      a long-range electric-field-induced capillary attraction between the particles,
      detected by other authors. Deviation from the logarithmic dependence is observed
      at short distances from the particle surface due to the electric pressure
      difference across the meniscus. The latter effect gives rise to an additional
      short-range contribution to the capillary interaction between two floating
      particles. The above conclusions are valid for either planar or spherical fluid
      interfaces, including emulsion drops. The electrodipping force, and the related
      long-range capillary attraction, can engender two-dimensional aggregation and
      self-assembly of colloidal particles. These effects could have implications for
      colloid science and the development of new materials.

PMID- 15248697
TI  - Absolute aggregation rate constants in aggregation of kaolinite measured by
      simultaneous static and dynamic light scattering.
AB  - The aggregation rate was determined for the < 0.2 microm size fraction of
      kaolinite (KGa-2) using simultaneous static and dynamic light scattering at pH
      9.5. It was found that method suggested by Holthoff et al. [Langmuir 1996, 12,
      5541] is suitable for determination of the absolute aggregation rate constant of
      a clay dispersion without using the particle optical factors. The determined fast
      aggregation rate constant is k11,fast = (3.7 +/- 0.2) x 10(-18) m3 s(-1).
      Stability behavior of kaolinite colloids was studied as a function of
      concentration of sodium chloride by simultaneous static and dynamic scattering.
      The critical aggregation concentration was found to be 0.085 +/- 0.005 mol dm(
      3). When calculating the relationship between the stability ratio and the
      electrolyte concentration using the DLVO theory, the best fit to the experimental
      data was achieved with a Hamaker constant of A = (4.7 +/- 0.2) x 10(-20) J.

PMID- 15248698
TI  - Excited-state proton transfer in complexes of poly(methacrylic acid) with
      dodecyltrimethylammonium chloride.
AB  - Proton-transfer reactions in aqueous solutions of poly(methacrylic acid) (PMA)
      were studied using a fluorescent probe and Fourier transform infrared (FTIR)
      spectroscopy. Protolytic photodissociation of 1-hydroxypyrene (HP) in water was
      found to be very slow. The PMA polyanion appeared to be very inefficient as a
      proton acceptor in the excited-state reaction with HP. However, a drastic
      increase in the deprotonation efficiency was observed in PMA solutions with the
      same pH values close to neutral when dodecyltrimethylammonium chloride (DTAC) was
      added. The protonated form of HP, as well as its anion, was shown to be
      solubilized in polyion-covered micelles. Time-resolved fluorescence data
      suggested at least two localization sites with different reactivities toward PMA.
      FTIR spectroscopy was used to quantify the degree of ionization of PMA in PMA
      DTAC mixtures. The IR data indicated that protolytic dissociation of PMA could be
      well described by the Henderson-Hasselbach equation with an apparent pK of 6.6.
      In contrast, the fluorescent data revealed cooperative protonation of the PMA
      groups interacting with HP localized within surfactant assemblies. This selective
      protonation at a pH close to neutral may be associated with a conformational
      transition in the polymer-surfactant complex.

PMID- 15248699
TI  - Interactions of complementary PEGylated liposomes and characterization of the
      resulting aggregates.
AB  - The interaction of complementary liposomes bearing both recognizable and
      protective ligands at their external surface has been investigated. Aggregation
      of hydrogenated phosphatidyl choline/cholesterol (2:1 molar ratio) based
      liposomes was mediated by the molecular recognition of the complementary
      phosphate and guanidinium groups incorporated in separate unilamellar liposomes.
      The phosphate group was incorporated in the bilayer employing dihexadecyl
      phosphate, while the guanidinium moiety was introduced in the membrane through
      the incorporation of various guanidinium lipids. For the latter, anchoring
      ability and primarily introduction of a spacer group between their lipophilic
      part and the guanidinium group was found to affect the ability for molecular
      recognition. Also, poly(ethylene glycol) (PEG) introduced in both types of
      liposomes at various concentrations and up to 15% with respect to cholesterol
      modifies the interaction effectiveness and morphology of the obtained aggregates.
      Interaction of these complementary liposomes leads to large precipitating
      aggregates or fused liposomes, as shown by phase contrast microscopy and dynamic
      light scattering. Specifically, fusion of liposomes takes place under a
      nonleaking process involving lipid mixing, as demonstrated by calcein entrapment
      and resonance energy transfer experiments. Calorimetric parameters also correlate
      with the processes of aggregation and fusion. The interactions of non-PEGylated
      liposomes involve exothermic processes of higher enthalpic content than those of
      the PEGylated counterparts.

PMID- 15248700
TI  - Nearly uniform MgO-supported pentaosmium cluster catalysts.
AB  - [Os5C(CO)14]2- was synthesized on the surface of MgO by reductive carbonylation
      of adsorbed Os3(CO)12 at 548 K and 1 bar. The supported species were
      characterized by infrared (IR), 13C NMR, and extended X-ray absorption fine
      structure (EXAFS) spectroscopies. The IR and EXAFS data are consistent with the
      presence of [Os5C(CO)14]2-, formed in a yield of about 65%, along with smaller
      osmium carbonyl clusters. As the supported clusters were decarbonylated in
      flowing He or H2, they were characterized by IR and EXAFS spectroscopies, which
      indicate that the decarbonylation was complete after each treatment at 573 K. The
      EXAFS data characterizing the sample treated in He determine an Os-Os first-shell
      coordination number of 3.4, matching that of [Os5C(CO)14]2- and indicating that
      the Os5C frame was retained after decarbonylation in He. Treatment of MgO
      supported [Os5C(CO)14]2- in H2 at 573 K resulted in the formation of aggregated
      osmium clusters larger than Os5C. The catalytic activity of Os5C for toluene
      hydrogenation was found to be an order of magnitude less than that of the
      aggregated osmium clusters, which are metallic in character.

PMID- 15248701
TI  - Surface activity of myristic acid in the poly(methyl methacrylate)/supercritical
      carbon dioxide system.
AB  - To confirm the surface activity of myristic acid in the dispersion polymerization
      of vinyl monomers in scCO2, the interfacial tension (IFT) at the
      polymer/supercritical carbon dioxide (scCO2) interface has been measured. For the
      IFT measurements, a high-pressure pendant drop apparatus was constructed. The IFT
      data was obtained by the axisymmetric drop shape analysis of melt polymer
      droplets formed at the tip of a capillary. The reliability of the apparatus was
      confirmed by measuring the IFT of polystyrene (PS)/scCO2 and polypropylene
      (PP)/CO2 systems. The IFT of the poly(methyl methacrylate) (PMMA)/scCO2 system
      with and without myristic acid was also measured. The IFT decreased on addition
      of myristic acid. The magnitude of the IFT depression due to the myristic acid
      was comparable to that of PS/scCO2 systems with the block copolymer surfactant,
      PS-b-poly(fluorooctyl acrylate). The surface activity of the myristic acid was
      confirmed by the decrease of IFT.

PMID- 15248702
TI  - X-ray and neutron reflectometry investigation of Langmuir-Blodgett films of
      cellulose ethers.
AB  - Langmuir-Blodgett films of a series of cellulose ethers are investigated by X-ray
      and neutron reflectometry. Two types of samples are considered: simple alkyl
      ethers of cellulose and derivatives obtained by the alkylation of (2
      hydroxypropyl)cellulose (HPC). All of the cellulose ethers form stable monolayers
      at the air-water interface. Significant differences are, however, found in the
      surface pressure-area compression isotherms. Ethers prepared from HPC typically
      exhibit larger limiting molecular areas and higher surface pressures than the
      corresponding simple cellulose ethers. The ease of monolayer transfer to
      hydrophobic silicon substrates differs greatly from one type of molecule to
      another. Successful transfer conditions are found only for ethers that form
      stable monolayers at sufficiently high surface pressures. Surprisingly,
      deuterated HPC ethers, prepared for neutron reflectivity measurements, exhibit
      monolayer properties significantly different from those of their hydrogenated
      analogues. Although essentially identical limiting molecular areas are found, the
      surface pressure corresponding to a characteristic plateau transition in the
      compression isotherm is found to decrease by about 8-10 mN m(-1) upon side chain
      deuteration. X-ray reflectivity results show a linear increase of film thickness
      with the number of deposited layers, indicating a regular and reproducible
      transfer. Observed average layer spacings are, however, significantly smaller
      than the calculated length of fully extended side chains. Neutron reflectivity
      curves recorded for composite LB films composed of both deuterated and
      hydrogenated polymers exhibit regular Keissig fringes, but no Bragg peak. This
      result indicates that these LB films do not possess an internal periodic
      structure and the initial layer-by-layer organization is lost by large interlayer
      diffusion.

PMID- 15248703
TI  - Structural and chemical characterization of monofluoro-substituted
      oligo(phenylene-ethynylene) thiolate self-assembled monolayers on gold.
AB  - Monolayers of oligo(phenylene-ethynylene) (OPE) molecules have exhibited promise
      in molecular electronic test structures. This paper discusses films formed from a
      novel molecule within this class, 2-fluoro-4-phenylethynyl-1-[(4
      acetylthio)phenylethynyl]benzene (F-OPE). The conditions of self-assembled
      monolayer (SAM) formation were systematically altered to fabricate reproducible
      high-quality molecular monolayers from the acetate-protected F-OPE molecule.
      Detailed characterization of the F-OPE monolayers was performed by using an array
      of surface probes, including reflection absorbance infrared spectroscopy (RAIRS),
      contact angle (CA) measurements, spectroscopic ellipsometry (SE), X-ray
      photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS),
      and atomic force microscopy (AFM). XPS and RAIRS established that the SAM formed
      without removal of the F substituent and without oxidation of the thiol. The
      monolayer thickness, determined from SE and AFM based nanolithography, was
      consistent with the formation of a densely packed monolayer. The valence
      electronic structure of the SAM was consistent with an aromatic structure shifted
      by the electron-withdrawing fluorine substituent and intermolecular coupling
      within an oriented array of molecules.

PMID- 15248704
TI  - Structural characterization of microcontact printed arrays of hexa(ethylene
      glycol)-terminated alkanethiols on gold.
AB  - This paper reports on the structural characteristics of microcontact printed
      oligo(ethylene glycol)-terminated alkanethiol layers, HS(CH2)15CONH-(CH2CH2O)6-H
      (hereafter EG6), on gold. Microwetting, contact angle goniometry, imaging null
      ellipsometry, and infrared reflection-absorption spectroscopy (IRAS) are used to
      characterize the printed EG6 layers, and the quality of these layers in terms of
      layer thickness and the crystallinity of the alkyl and ethylene glycol portions
      is compared with data obtained from analogous layers prepared by solution self
      assembly. The outcome of the printing process is critically dependent on the
      experimental parameters used to prepare the patterns. It is found that high
      quality layers, consisting of densely packed all-trans alkyl chains terminated
      with relatively helical hexa(ethylene glycol) tails, are formed by inking the
      poly(dimethylsiloxane) (PDMS) stamp with a 1 mM EG6 solution and contacting it
      with gold for 15 min. The homogeneity of printed layers is not as good as the
      homogeneity of those prepared from solution under similar conditions, most likely
      because of simultaneous transfer of low molecular weight residues from the PDMS
      stamp. These residues, however, can be easily removed upon ultrasonication in
      ethanol without affecting the quality of the printed layer. Further on, the
      microscopic square-shaped bare gold patterns formed after microcontact printing
      (muCP) are subsequently filled with 16-hexadecanoic acid (hereafter THA) or
      HS(CH2)15CONH-(CH2CH2O)6-COOH (hereafter EG6COOH) to provide a microarray
      platform for further covalent attachment of biomolecules. Well-defined structures
      in terms of wettability contrast, sharpness, and height differences between the
      printed and back-filled areas are confirmed by imaging null ellipsometry and
      microscopic wetting.

PMID- 15248705
TI  - Micro- and nanofabrication of robust reactive arrays based on the covalent
      coupling of dendrimers to activated monolayers.
AB  - We report on methods to fabricate robust micro- and nanopatterned platforms,
      comprising high functional group densities and quasi three-dimensional
      structures, for possible applications in biochip array technologies. For this
      purpose, amine-terminated poly(amidoamine) (PAMAM) dendrimers were immobilized
      via amide linkage formation on 11,11'-dithiobis(N-hydroxysuccinimidylundecanoate)
      (NHS-C10) self-assembled monolayers (SAMs) on gold surfaces. The coupling
      reaction and the resulting assemblies were characterized by grazing incidence
      reflection Fourier transform infrared spectroscopy, contact angle measurements, X
      ray photoelectron spectroscopy (XPS), and atomic force microscopy; the obtained
      surface coverage values were successfully fitted with a Langmuir isotherm. The
      fraction of unreacted peripheral primary amine groups of the surface-immobilized
      PAMAM dendrimers was 28% as determined by XPS analysis of trifluoroacetic
      anhydride-labeled assemblies. Patterning of the PAMAM dendrimers on NHS-C10 SAMs
      on the micrometer and sub-100-nm scale was achieved by microcontact printing and
      dip pen nanolithography. The resulting patterns are characterized by their high
      degree of order and stability of the transferred molecules due to covalent
      attachment.

PMID- 15248706
TI  - MMA/DVB emulsion surface graft polymerization initiated by UV light.
AB  - Methyl methacrylate/1,2-divinylbenzene (MMA/DVB) in an opaque emulsion were
      successfully grafted onto the surface of polymeric substrate under the
      irradiation of UV light with benzophenone (BP) as a photoinitiator that was
      previously coated on the substrate surface. Monomer conversion, grafting
      efficiency, and grafting yields were determined by the gravimetric method. ATR
      IR, AFM, and TEM were used to characterize the surface composition, to observe
      the topography of the grafted substrates, and to view inter-film colloid
      particles formed by cross-linking. The results reveal that, with the opaque
      MMA/DVB emulsion system and CPP film as substrate, the monomer conversion is in
      the range of 15-55%, the grafting efficiency is about 80%, the grafting yield
      reaches 5%, and the thickness of the graft layer can be controlled in the range
      0.09-1.5 microm. Images of AFM show that the graft layer is piled up by
      nanoparticles (about 30-50 nm in diameter), which are linked together and tied to
      the substrate surface with covalent bonds. A possible model of surface graft
      polymerization including surface initiating, nucleation, and shish kebab growing
      is put forward to interpreting the above results.

PMID- 15248707
TI  - Substrate-induced modulation of the Raman scattering signals from self-assembled
      organic nanometric films.
AB  - Raman scattering signals recorded by microscopy from organic self-assembled
      monolayers (thin nanometric films of calibrated thickness) on silica substrates
      were found to be much stronger than those obtained from identical films assembled
      on bulk silicon substrates. This effect, observed in the backscattering geometry,
      is shown to result from interferences between the direct and reflected beams
      (including both the excitation and scattered radiation) in front of a smooth
      reflecting surface. Strong dependence of the effect on the distance between the
      sampled monolayer and the bulk silicon substrate allows enhancement of the Raman
      signals of organic monolayer films on silicon by factors up to approximately 70
      by using appropriate silica spacers. The dependence of the Raman signal intensity
      on film thickness was also studied for thicker nanometric films comprising a
      series of self-assembled organosilane multilayers on bulk silicon and fused
      silica substrates, and the predicted deviation from linearity in the case of the
      silicon substrate is experimentally confirmed.

PMID- 15248708
TI  - Evaluation of an atomic force microscopy pull-off method for measuring molecular
      weight and polydispersity of polymer brushes: effect of grafting density.
AB  - The accuracy of the molecular weights Mn and polydispersities of polymer brushes,
      determined by stretching the grafted chains using atomic force microscopy (AFM)
      and measuring the contour length distribution, was evaluated as a function of
      grafting density sigma. Poly(N,N-dimethylacrylamide) brushes were prepared by
      surface initiated atom transfer radical polymerization on latex particles with
      sigma ranging between 0.17 and 0.0059 chains/nm2 and constant Mn. The polymer,
      which could be cleaved from the grafting surface by hydrolysis and characterized
      by gel permeation chromatography (GPC), had a Mn of 30,600 and polydispersity
      (PDI) of 1.35. The Mn determined by the AFM technique for the higher density
      brushes agreed quite well with the GPC results but was significantly
      underestimated for the lower sigma. At high grafting density in good solvent, the
      extended structure of the brush increases the probability of forming segment-tip
      contacts located at the chain end. When the distance between chains approached
      twice the radius of gyration of the polymer, the transition from brush to
      mushroom structure presumably enabled the formation of a larger number of segment
      tip contacts having separations smaller than the contour length, which explains
      the discrepancy between the two methods at low sigma. The PDI was typically
      higher than that obtained by GPC, suggesting that sampling of chains with above
      average contour length occurs at a frequency that is greater than their spatial
      distribution.

PMID- 15248709
TI  - Mixed thin films of a cationic amphiphilic porphyrin and n-alkanes.
AB  - Langmuir and Langmuir-Blodgett (LB) films of a cationic amphiphilic porphyrin
      mixed with n-alkanes octadecane and hexatriacontane were prepared and
      characterized, to examine the influence of the alkanes on film structure and
      stability. While the structure present in these films was controlled primarily by
      the porphyrin, the addition of the alkanes resulted in significant changes to
      both the phase behavior of the Langmuir films and the molecular arrangement of
      the LB films. These changes, as well as the observed chain length effects, are
      explained in terms of the intermolecular interactions present in the films.

PMID- 15248711
TI  - Enantiomeric recognition of amino acids by amphiphilic crown ethers in Langmuir
      monolayers.
AB  - Four new chiral, amphiphilic crown ethers differing by the hydrophobic tailgroups
      were synthesized, and their capacity to recognize enantiomeric amino acids was
      examined using Langmuir films. Surface pressure and surface potential
      measurements performed on the subphases containing L or D enantiomers of alanine,
      valine, phenylglycine, and tryptophane indicate that the crown ethers forming the
      monolayer interact with the amino acids. The effects observed are ascribed to the
      formation of host-guest complexes. The differences in the magnitude of the
      effects measured show that the crown ethers are capable of discriminating between
      different amino acids as well as the enantiomers. Our results demonstrate that
      the structure of the monolayer plays a decisive role in the molecular recognition
      process including chiral recognition.

PMID- 15248710
TI  - X-ray studies of self-assembled organic monolayers grown on hydrogen-terminated
      Si(111).
AB  - The structure of self-assembled monolayers (SAMs) of undecylenic acid methyl
      ester (SAM-1) and undec-10-enoic acid 2-bromo-ethyl ester (SAM-2) grown on
      hydrogen-passivated Si(111) were studied by X-ray reflectivity (XRR), X-ray
      standing waves (XSW), X-ray fluorescence (XRF), atomic force microscopy, and X
      ray photoelectron spectroscopy (XPS). The two different SAMs were grown by
      immersion of H-Si(111) substrates into the two different concentrated esters. UV
      irradiation during immersion was used to create Si dangling bond sites that act
      as initiators of the surface free-radical addition process that leads to film
      growth. The XRR structural analysis reveals that the molecules of SAM-1 and SAM-2
      respectively have area densities corresponding to 50% and 57% of the density of
      Si(111) surface dangling bonds and produce films with less than 4 angstroms root
      mean-square roughness that have layer thicknesses of 12.2 and 13.2 angstroms.
      Considering the molecular lengths, these thicknesses correspond to a 38 degrees
      and 23 degrees tilt angle for the respective molecules. For SAM-2/Si(111)
      samples, XRF analysis reveals a 0.58 monolayer (ML) Br total coverage. Single
      crystal Bragg diffraction XSW analysis reveals (unexpectedly) that 0.48 ML of
      these Br atoms are at a Si(111) lattice position height that is identical to the
      T1 site that was previously found by XSW analysis for Br adsorbed onto Si(111)
      from a methanol solution and from ultrahigh vacuum. From the combined XPS, XRR,
      XRF, and XSW evidence, it is concluded that Br abstraction by reactive surface
      dangling bonds competes with olefin addition to the surface.

PMID- 15248712
TI  - Adsorption and diffusion of molecular nitrogen in single wall carbon nanotubes.
AB  - Using molecular simulation, the adsorption and self-diffusion of diatomic
      nitrogen molecules inside a single wall carbon nanotube have been studied over a
      range of nanotube diameters (8.61-15.66 A) and loadings at temperatures of 100
      and 298 K. Nitrogen adsorption energy is found to increase as the nanotube
      diameter is reduced toward the molecular diameter of nitrogen. A discrete
      organization of the nitrogen into adsorbed layers is observed at high loadings
      that follows a regular progression determined primarily by geometric
      considerations. The formation of an adsorbate core at the center of the nanotube
      is found to increase the self-diffusion of nitrogen. A "wormlike" phase is found
      for the adsorbed nitrogen in the (15, 0) carbon nanotube at high loadings and at
      100 K.

PMID- 15248713
TI  - Grafting of single, stimuli-responsive poly(ferrocenylsilane) polymer chains to
      gold surfaces.
AB  - Redox-responsive poly(ferrocenylsilane) (PFS) polymer molecules were attached
      individually to gold surfaces for force spectroscopy experiments on the single
      molecule level. By grafting ethylenesulfide-functionalized PFS into the defects
      of preformed self-assembled monolayers (SAMs) of different omega-mercaptoalkanols
      on Au(111), the surface coverage of PFS macromolecules could be conveniently
      controlled. Atomic force microscopy (AFM), contact angle, as well as cyclic and
      differential pulse voltammetry measurements were carried out to characterize the
      morphology, wettability, and surface coverage of the grafted layers. The values
      of the PFS surface coverage were found to depend on the chain length of the omega
      mercaptoalkanol molecules and on the concentration of the PFS solution but not on
      the insertion time or on the molar mass of PFS. The equilibrium surface coverages
      were successfully described by Langmuir adsorption isotherms. For low-surface
      coverage values (< 6.2 x 10(-4) chain/nm2), achieved by PFS insertion from very
      dilute solutions (8 x 10(-6) M) into long-chain SAMs, AFM and differential pulse
      voltammetry showed that surfaces exposing isolated individual polymer chains were
      obtained. The isolated PFS macromolecules were subjected to in situ AFM-based
      single molecule force spectroscopy (SMFS) measurements. The single chain
      elasticity of PFS in isopropanol (and ethanol) was fitted with the modified
      freely jointed chain (m-FJC) model. This procedure yielded a Kuhn segment length
      of 0.33 +/- 0.05 nm and a segment elasticity of 32 +/- 5 nN/nm.

PMID- 15248714
TI  - Controlling surface roughness in vapor-deposited poly(amic acid) films by solvent
      vapor exposure.
AB  - A series of vapor-deposited poly(amic acid) (PAA) films were exposed to dimethyl
      sulfoxide (DMSO) vapors to investigate sorption kinetics and surface smoothing
      phenomena. Gravimetric sorption and secondary-ion mass spectrometry (SIMS)
      results are both consistent with frontal (case II) diffusion. These experiments
      suggest that the solvent front is defined by a sharp interface that delineates
      the swollen material from the unswollen material. Solvent-vapor smoothing was
      studied by first depositing PAA onto rough aluminum surfaces, and then, during
      solvent-vapor exposure, the surface topology was continuously monitored using a
      light interference microscope. The resulting time-dependent power spectra
      indicate that high-frequency defects smooth faster than low-frequency defects.
      This frequency dependence was further investigated by depositing PAA onto a
      series of sinusoidal surfaces and exposing them to solvent vapor inside a flow
      channel. The sinusoidal amplitudes decay exponentially with time, with decay
      constants that are proportional to the surface frequency. To explain the physics
      of surface smoothing, a two-parameter model is presented and agrees qualitatively
      with experimental data.

PMID- 15248715
TI  - Surface phase behavior in Gibbs monolayers of bis(ethylene glycol) mono-n
      tetradecyl ether at the air-water interface.
AB  - We present the adsorption kinetics and surface morphology of the adsorbed
      monolayers of bis(ethylene glycol) mono-n-tetradecyl ether (C14E2) by film
      balance and Brewster angle microscopy. A cusp point followed by a plateau region
      in the pressure (pi)-time (t) adsorption isotherm indicates a first-order phase
      transition in the coexistence region between a lower density liquid expanded (LE)
      phase and a higher density liquid condensed (LC) phase. A variety of condensed
      phase domains surrounded by the homogeneous LE phase are observed just after the
      appearance of the phase transition. The domains are of a spiral or striplike
      structure at lower temperatures. This characteristic shape of the domains is
      because of strong dipole-dipole repulsion between the molecules. At 18 degrees C,
      the domains are found to be quadrant structures. A slight increase in subphase
      temperature (around 1 degrees C) brings about a quadrant-to-circular shape
      transition in the domains. The circular domains return to quadrant structures as
      the subphase temperature is lowered. The domains completely disappear when the
      temperature is increased beyond 19 degrees C, suggesting that the critical
      temperature for the condensed domain formation is 19 degrees C. Above this
      temperature, the hypothetical surface pressure necessary for the phase transition
      exceeds the actual surface pressure attainable from a solution of concentration
      greater than or equal to the critical micelle concentration. An increase in
      molecular motion with increasing temperature results in a higher degree of chain
      flexibility. As a result, the molecules cannot accumulate in the condensed phase
      form when the subphase temperature is above 19 degrees C.

PMID- 15248716
TI  - Efficient photosensitized degradation of 4-chlorophenol over immobilized aluminum
      tetrasulfophthalocyanine in the presence of hydrogen peroxide.
AB  - The photosensitized degradation of 4-chlorophenol (4-CP) under visible light
      (lambda > or = 450 nm) irradiation in an aerated aqueous medium at pH 12 was
      studied using an immobilized photosensitizer, aluminum tetrasulfophthalocyanine,
      on a commercial resin Amberlite IRA 400. The catalyst exhibited strong adsorption
      toward 4-CP, but the adsorption led to an exponential decrease in both the
      initial rate and the apparent first-order rate constant, as measured by 4-CP loss
      in the bulk solution. Several intermediates were formed from 4-CP oxidation,
      including fumaric acid, benzoquinone, and hydroquinone, which were adsorbed
      strongly on the catalyst and lowered the photosensitized reaction. Addition of
      H2O2 was found to be an efficient way to eliminate the colored intermediates and
      consequently recover the catalyst activity. The immobilized sensitizer was stable
      and could be used repeatedly in the presence of H2O2. The optimal loading of the
      photosensitizer in the catalyst was about 1.0 wt %.

PMID- 15248717
TI  - Interaction of anhydride and carboxylic acid compounds with aluminum oxide
      surfaces studied using infrared reflection absorption spectroscopy.
AB  - The chemical bonding of three different anhydride and carboxylic acid based
      compounds with a set of differently prepared aluminum substrates has been
      investigated using infrared reflection absorption spectroscopy. The compounds
      were selected to model typically used adhesives, coatings, and self-assembling
      monolayers. The purpose of the investigation was to study the interaction of
      these functional groups with the aluminum oxide surface and to determine whether
      this interaction is influenced by the changes in chemistry and composition of the
      oxide layer. The extent to which the compounds resisted disbondment in water was
      also investigated. The oxide layers on the differently prepared substrates were
      all found to be capable of hydrolysis of the anhydride group, resulting in the
      formation of two carboxylic acid groups. Subsequently, both of the carboxylic
      acid groups became deprotonated, to form a coordinatively bonded carboxylate
      species. The same behavior was also observed for monofunctional carboxylic acids.
      For all different oxides layers, the carboxylate was found to be coordinated in a
      bridging bidentate way to two aluminum cations in the oxide layer. The oxide
      layers showed however clear differences in the amount of molecules being
      chemisorbed. A relation was established with the amount of hydroxyls present on
      their surfaces, as determined from X-ray photoelectron spectroscopy measurements.
      The coordinative bonding of a monofunctional carboxylic acid group to the oxide
      surface was found to be not stable in the presence of water, while a bifunctional
      carboxylic acid group could resist displacement by water for a prolonged period
      of time.

PMID- 15248718
TI  - Interaction of ester functional groups with aluminum oxide surfaces studied using
      infrared reflection absorption spectroscopy.
AB  - The bonding of two types of ester group-containing molecules with a set of
      different oxide layers on aluminum has been investigated using infrared
      reflection absorption spectroscopy. The different oxide layers were made by
      giving typical surface treatments to the aluminum substrate. The purpose of the
      investigation was to find out what type of ester-oxide bond is formed and whether
      this is influenced by changes in the composition and chemistry of the oxide. The
      extent by which these bonded ester molecules resisted disbondment in water or
      substitution by molecules capable of chemisorption was also investigated. The
      ester groups were found to show hydrogen bonding with hydroxyls on the oxide
      surfaces through their carbonyl oxygens. For all oxides, the ester groups showed
      the same nu(C = O) carbonyl stretching vibration after adsorption, indicating
      very similar bonding occurs. However, the oxides showed differences in the amount
      of molecules bonded to the oxide surface, and a clear relation was observed with
      the hydroxyl concentration present on the oxide surface, which was determined
      from XPS measurements. The two compounds showed differences in the free to bonded
      nu(C = O) infrared peak shift, indicating differences in bonding strength with
      the oxide surface between the two types of molecules. The bonding of the ester
      groups with the oxide surfaces was found to be not stable in the presence of
      water and also not in the presence of a compound capable of chemisorption with
      the aluminum oxide surface.

PMID- 15248719
TI  - Flow-induced molecular segregation in beta-casein-monoglyceride mixed films
      spread at the air-water interface.
AB  - In this work, we have used different and complementary interfacial techniques
      (surface film balance, Brewster angle microscopy, and interfacial shear rheology)
      to analyze the static (structure, topography, reflectivity, miscibility, and
      interactions) and flow characteristics (surface shear characteristics) of beta
      casein and monoglyceride (monopalmitin and monoolein) mixed films spread on the
      air-water interface. The structural, topographical, and shear characteristics of
      the mixed films depend on the surface pressure and on the composition of the
      mixed film. The surface shear viscosity (etas) varies greatly with the surface
      pressure. In general, the greater the surface pressure, the greater the values of
      etas. At higher surface pressures, collapsed beta-casein residues may be
      displaced from the interface by monoglyceride molecules with important
      repercussions on the shear characteristics of the mixed films. A shear-induced
      change in the topography of monoglyceride and beta-casein domains, on one hand,
      and a segregation between domains of the film-forming components, on the other
      hand, were also observed. The displacement of the beta-casein by the
      monoglycerides is facilitated under shear conditions, especially for beta-casein
      monoolein mixed films.

PMID- 15248720
TI  - Interactions of selenate with copper(I) oxide particles.
AB  - The chemical mechanisms responsible for the immobilization of selenate (SeO4(2-)
      from aqueous solutions on cuprite (Cu2O) particles were determined from batch
      experiments. This was achieved by performing both solution-phase analyses and
      characterization of solid particles by X-ray photoelectron spectroscopy and
      transmission electron microscopy techniques, after equilibration of cuprite
      particles with selenate-containing solutions at various pH values, solid-to
      solution ratios, and ionic strengths. Two distinct mechanisms have been pointed
      out. In the acidic medium, where the acid-catalyzed dissolution of cuprite into
      CuI species occurs, the immobilization of selenate implies a redox reaction with
      transient CuI leading to the precipitation of copper(II) selenite, CuSeO3. In the
      absence of protons added in the medium, Cu2O is chemically stable and
      immobilization of SeO4(2-) is essentially due to adsorption in the form of an
      outer-sphere surface complex. The uptake level of selenate by Cu2O is markedly
      lower than that observed for selenite species in the same conditions.

PMID- 15248721
TI  - The outermost atomic layer of thin films of fluorinated polymethacrylates.
AB  - In this paper, we investigate the surface properties of a series of copolymers of
      perfluoroalkyl methacrylate (CH2 = C(CH3)COOCH2CnF(2n + 1), n = 1, 6, or 10) and
      methyl methacrylate (MMA) and of blends of perfluorooctyl-end-capped poly(methyl
      methacrylate) (PMMA) and pure PMMA. The introduction of perfluoroalkyl groups
      significantly lowers the polymer surface energy as determined by the acid-base
      approach. X-ray photoelectron spectroscopy (XPS) confirms a higher fluorine
      concentration in the surface region (the outer 3.8 nm) as compared to in the
      bulk. The fluorine density in the outermost atomic layer is quantitatively
      determined by low-energy ion scattering (LEIS). A linear relationship is found
      between the fluorine density in the outermost atomic layer and the surface energy
      of the partially fluorinated polymethacrylates, irrespective of the length of the
      perfluoroalkyl chain. This linearity confirms Langmuir's "principle of
      independent surface action". Deviation from this linear relationship exists for
      both highly and sparsely fluorinated polymethacrylates and can be ascribed to the
      local (surface) ordering of the fluorinated tails and MMA units, respectively.
      This study may offer one further step toward a deeper understanding of the
      correlations between macroscopic surface properties and microscopic surface
      chemical composition.

PMID- 15248722
TI  - Foam films stabilized by dodecyl maltoside. 1. Film thickness and free energy of
      film formation.
AB  - Foam films stabilized by a sugar-based nonionic surfactant, beta-dodecyl
      maltoside, are investigated. The film thickness and the film contact angle (which
      is formed at the transition between the film and the bulk solution) are measured
      as a function of NaCl concentration, surfactant concentration, and temperature.
      The film thickness measurements provide information about the balance of the
      surface forces in the film whereas the contact angle measurements provide
      information about the specific film interaction free energy. The use of the glass
      ring cell and the thin film pressure balance methods enables studies under a
      large variety of conditions. Thick foam films are formed at low electrolyte
      concentration. The film thickness decreases (respectively the absolute value of
      the interaction film free energy increases) with the increase of the electrolyte
      concentration according to the classical DLVO theory. This indicates the
      existence of a repulsive double layer electrostatic component of the disjoining
      pressure. An electrostatic double layer potential of 16 mV was calculated from
      the data. A decrease of the film thickness on increase of the surfactant
      concentration in the solution is observed. The results are interpreted on the
      basis of the assumption that the surface double layer potential originates in the
      adsorption of hydroxyl ions at the film surfaces. These ions are expelled from
      the surface at higher surfactant concentration.

PMID- 15248723
TI  - Hidden electrochemistry in the thermal grafting of silicon surfaces from grignard
      reagents.
AB  - Covalent grafting of alkyl chains on silicon can be obtained by thermal treatment
      in Grignard reagents. Alkyl halide present in the Grignard solution as an
      impurity appears to play a key role in the grafting process. Grafting efficiency
      is improved when the alkyl halide concentration is increased. It is also enhanced
      on n-type substrates as compared to p-type substrates and when alkyl bromides are
      present in solution rather than alkyl chlorides. The grafting reaction involves a
      zero-current electrochemical step. A reaction model in which simultaneous
      Grignard oxidation and alkyl halide reduction take place at the silicon surface
      accounts for all these observations. Alkyl halide reduction is the rate
      determining step. Negative charging of the silicon surface lowers the energetic
      barrier for this reaction, allowing for efficient grafting on n-Si.

PMID- 15248724
TI  - Rational design of original materials for the electrocatalytic hydrogenation
      reactions: concept, preparation, characterization, and theoretical analysis.
AB  - Original and versatile new materials for the electrocatalytic hydrogenation of
      organic compounds were designed. The materials consist of reticulated glassy
      carbon cathode electrodes in which the modified silica particles (average
      diameter 40-63 microm) were dynamically circulated. The modification of the
      silica surface is 2-fold. First, the silica is surface-modified using organic
      functions such as -OSi(CH3)2(CH2)3OCH2CH-(OH)(CH)2OH (SiO2-Diol), 
      OSi(CH3)2(CH2)7CH3 (SiO2-C8), and -OSi(CH3)2C6H5 (SiO2-Phenyl). Second, these
      silica particles were further modified by vapor phase deposition of nickel
      nanoaggregates (used as sites for hydrogen atoms and electric contacts with the
      electrode material), which does not destroy or alter the organic
      functionalization as demonstrated by thermogravimetric analysis-mass spectrometry
      and Raman, diffuse reflectance IR Fourier transform, and Auger electron
      spectroscopies. The new concept stems from relative adsorption and desorption
      properties of the organic molecules and their corresponding reduced products into
      the organic functionalization of the surface-modified silica. In this work, the
      electrocatalytic hydrogenation cyclohexanone was used to test the concept. The
      performances (amount of cyclohexanol vs time of generated electrolysis at
      constant current) are measured and compared for the various bonded organic
      functions of the silica surface listed above, along with the unmodified silica
      particles (but still containing nickel nanoaggregates) and the presence or
      absence of methanol in solution. The measurements of the adsorption isotherms of
      cyclohexanone, and the calculations of the interaction energies (MM3 force field)
      between the chemisorbed organic functions and the substrates, corroborate
      perfectly the electrocatalysis results.

PMID- 15248725
TI  - Measurement of enzyme kinetics using microscale steady-state kinetic analysis.
AB  - This paper describes a new technique--microscale steady-state kinetic analysis
      (microSKA)--that enables the rapid and parallel analysis of enzyme kinetics.
      Rather than physically defining a microscopic reactor through microfabrication,
      we show how the relative rates of reaction and transport in a macroscopic flow
      chamber, where the enzyme is immobilized on one wall of the chamber, results in
      the confinement of an enzyme-catalyzed reaction to a microscopic reactor volume
      adjacent to this wall. This volume has linear dimensions that are orders of
      magnitude smaller than the physical dimensions of the system (i.e., micrometer vs
      millimeter). Conversion within this volume is monitored at steady state as a
      function of position, rather than time. In this way, limitations due to reactor
      dead time and mixing are avoided. We use microSKA to determine kinetic parameters
      for the alkaline phosphatase-catalyzed de-phosphorylation of nonfluorescent
      methylumbelliferyl phosphate (MUP) to fluorescent 7-hydroxy-4-methylcoumarin
      (HMC) at two different values of pH. Kinetic parameters measured with microSKA
      are in good agreement with values obtained using conventional methods, if one
      takes into account effects of immobilization on enzyme activity. This technique
      provides a rapid and simple method for determining enzyme kinetics using small
      amounts of sample material and may be useful for applications in proteomics, drug
      discovery, biocatalyst development, and clinical diagnostics.

PMID- 15248726
TI  - Carbonate formation on bioactive glasses.
AB  - The system termed 58S is a sol-gel-synthesized bioactive glass composed of SiO2,
      CaO, and P2O5, used in medicine as bone prosthetic because, when immersed in a
      physiological fluid, a layer of hydroxycarbonate apatite is formed on its
      surface. The mechanism of bioactive glass 58S carbonation was studied in the
      vacuum by means of in-situ FTIR spectroscopy with the use of CO2, H2O, and CD3CN
      as probe molecules. The study in the vacuum was necessary to identify both the
      molecules specifically involved in the carbonation process and the type of
      carbonates formed. Bioactive glass 58S was compared to a Ca-doped silica and to
      CaO. On CaO, ionic carbonates could form by contact with CO2 alone, whereas on
      58S and on Ca-doped silica carbonation occurred only if both CO2 and an excess of
      H2O were present on the sample. The function of H2O was not only to block surface
      cationic sites, so that CO2 could not manifest its Lewis base behavior, but also
      to form a liquid-like (mono)layer that allowed the formation of carbonate ions.
      The presence of H2O is also supposed to promote Ca2+ migration from the bulk to
      the surface. Carbonates formed at the surface of CaO and of Ca-bearing silicas
      (thus including bioactive glasses) are of the same type, but are produced through
      two different mechanisms. The finding that a water excess is necessary to start
      heavy carbonation on bioactive glasses seemed to imply that the mechanism leading
      to in-situ carbonation simulates, in a simplified and easy-to-reproduce system,
      what happens both in solution, when carbonates are incorporated in the apatite
      layer, and during sample shelf-aging.

PMID- 15248727
TI  - Diffusivity of whey protein and gum arabic in their coacervates.
AB  - Structural properties of whey protein (WP)/gum arabic (GA) coacervates were
      investigated by measuring the diffusivity of WP and GA in their coacervate phase
      as a function of pH by means of three different complementary techniques. The
      combination of these measurements revealed new insights into the structure of
      coacervates. Nuclear magnetic resonance (NMR) measured the self-diffusion
      coefficient of the GA in the coacervate phase prepared at various pH values.
      Fluorescence recovery after photobleaching (FRAP) was measured using a confocal
      scanning laser microscope. The WP and GA were covalently labeled with two
      different dyes. The time of fluorescence recovery, related to the inverse of the
      diffusion coefficient, was evaluated from the measurements, and the diffusivity
      of the WP and GA on a long time scale could be individually estimated at each pH
      value. Diffusing wave spectroscopy (DWS) combined with transmission measurement
      was carried out in the coacervate phase, and the diffusion coefficient,
      corresponding to the averaged diffusion of all particles that scattered in the
      system, was calculated as a function of pH. Independently of the technique used,
      the results showed that the diffusion of the WP and GA within the coacervate
      phase was reduced as compared to a diluted biopolymer mixture. NMR, DWS, and FRAP
      measurements gave similar results, indicating that the biopolymers moved the
      slowest in the coacervate matrix at pH 4.0-4.2. It is assumed that the diffusion
      of the WP and GA is reduced because of a higher electrostatic interaction between
      the biopolymers. Furthermore, FRAP results showed that in the coacervate phase WP
      molecules diffused 10 times faster than GA molecules. This result is very
      relevant because it shows that WP and GA move independently in the liquid
      coacervate phase. Finally, DWS measurements revealed that the coacervate phase
      rearranged with time, as evidenced by a decrease of the diffusion coefficient and
      a loss of the turbidity of the sample. A more homogeneous transparent coacervate
      phase was obtained after a few days/weeks. Faster rearrangement was obtained at
      pH 3.0 and 3.5 than at higher pH values.

PMID- 15248728
TI  - Novel molecular recognition via fluorescent resonance energy transfer using a
      biotin-PEG/polyamine stabilized CdS quantum dot.
AB  - A novel functionally PEGylated quantum dot (QD) was prepared by a coprecipitation
      method in the presence of the biotin-PEG/polyamine block copolymer. When CdCl2
      and Na2S were mixed in aqueous media in the presence of the biotin-PEG-b-poly(2
      (N,N-dimethylamino)ethyl methacrylate) [biotin-PEG/PAMA], a CdS QD with a size of
      ca. 5 nm was prepared. The polyamine segment was anchored on the surface of the
      formed CdS nanoparticle, whereas the PEG segment was tethered on the surface to
      form a hydrophilic palisade, thus improving the dispersion stability in aqueous
      media even under a high salt concentration condition. An effective fluorescent
      resonance energy transfer (FRET) was observed by the specific interaction of the
      biotin-PEG/PAMA stabilized CdS QD with TexasRed-labeled streptavidin of the
      physiological ionic strength of 0.15 M. The extent of the energy transfer was in
      proportion to the concentration of the TexasRed-streptavidin. This FRET system
      using the PEGylated CdS QD coupled with fluorescent-labeled protein can be
      utilized as a highly sensitive bioanalytical system.

PMID- 15248729
TI  - Adsorption of an endoglucanase from the hyperthermophilic Pyrococcus furiosus on
      hydrophobic (polystyrene) and hydrophilic (silica) surfaces increases protein
      heat stability.
AB  - The interaction of an endoglucanase from the hyperthermophilic microorganism
      Pyrococcus furiosus with two types of surfaces, that is, hydrophobic polystyrene
      and hydrophilic silica, was investigated, and the adsorption isotherms were
      determined. The adsorbed hyperthermostable enzyme did not undergo loss of
      biological activity. A model was proposed for the mechanism of interaction of the
      enzyme with the surface based on the shape of the adsorption isotherm, the
      morphological characteristics of the enzyme, and the thermodynamic parameters of
      the system. The enzyme was irreversibly immobilized at the solid/liquid interface
      even at high temperatures, and most interestingly, it acquired further heat
      stabilization upon adsorption. The denaturation temperature increased from 108
      degrees C in solution to 116 degrees C upon adsorption on hydrophilic silica
      particles. Adsorption on the hydrophobic polystyrene surface even shifted the
      denaturation temperature to 135 degrees C, the most extreme experimentally
      determined protein denaturation temperature ever reported. Maintenance of the
      biological function particularly at high temperatures is important for the
      development of solid substrate immobilized enzymes for applications in
      biocatalysis and biotechnology. This also presents an additional stabilization
      mechanism employed by nature where the extracellular hyperthermostable enzyme
      remains folded and active at the extreme temperatures of its natural environment
      by adsorption on the surface of rocks and other materials appearing in the
      surroundings of the microorganism.

PMID- 15248730
TI  - Influence of DNA adsorption and DNA/cationic surfactant coadsorption on the
      interaction forces between hydrophobic surfaces.
AB  - The forces between hydrophobic surfaces with physisorbed DNA are markedly and
      irreversibly altered by exposure to DNA/cetyltrimethylammonium bromide (CTAB)
      mixtures. In this colloidal probe atomic force microscopy study of the
      interactions between a hydrophobic polystyrene particle and an
      octadecyltrimethylethoxysilane-modified mica surface in sodium bromide solutions,
      we measure distinct changes in colloidal forces depending on the existence and
      state of an adsorbed layer of DNA or CTAB-DNA complexes. For bare hydrophobic
      surfaces, a monotonically attractive approach curve and very large adhesion are
      observed. When DNA is adsorbed at low bulk concentrations, a long-range repulsive
      force dominates the approach, but on retraction some adhesion persists and DNA
      bridging is clearly observed. When the DNA solution is replaced with a CTAB-DNA
      mixture at relative low CTAB concentration, the length scale of the repulsive
      force decreases, the adhesion due to hydrophobic interactions greatly decreases,
      and bridging events disappear. Finally, when the surface is rinsed with NaBr
      solution, the length scale of the repulsive interaction increases modestly, and
      only a very tiny adhesion remains. These pronounced changes in the force behavior
      are consistent with CTAB-induced DNA compaction accompanied by increased DNA
      adsorption, both of which are partially irreversible.

PMID- 15248731
TI  - Seeded high yield synthesis of short Au nanorods in aqueous solution.
AB  - Short gold nanorods of average lengths ranging between 20 and 100 nm (with
      corresponding aspect ratios of 2 and 4) were synthesized in excellent yield
      (approximately 97%). These nanorods were characterized by dark-field microscopy,
      UV-visible spectrophotometry, and transmission electron microscopy. Temporal
      evolution of rod shape had also been followed by UV-visible spectrophotometry and
      transmission electron microscopy and indicates that the nanorods briefly increase
      in length, then increase slightly in width, as they grow. The effect of the
      synthetic parameters on the rod dimension and yield was explored to find out
      suitable conditions to produce short nanorods; short nanorods have both plasmon
      bands in the visible region of the spectrum, which is a valuable property for
      sensor applications.

PMID- 15248732
TI  - Iron wheels on silicon: wetting behavior and electronic structure of adsorbed
      organostannoxane clusters.
AB  - Atomic force microscopy and synchrotron radiation (SR) spectroscopy have been
      used to study the wetting behavior and electronic structure of thin films of a
      novel organometallic cluster--[BuSn(O)OC(O)Fc]6 ("Fc" = ferrocenyl)--on silicon
      substrates. This cluster comprises six ferrocene units connected to a stannoxane
      central core--"an iron wheel on a tin drum" (V. Chandrasekhar; et al. Angew.
      Chem., Int. Ed. 2000, 39, 1833). Thin films spin-cast onto native oxide
      terminated silicon readily dewet the substrate. We have utilized advanced image
      analysis techniques based on Minkowski functionals to provide a detailed
      quantitative analysis of the morphology of the stannoxane overlayers. This
      analysis shows that the dewetting patterns are rather far removed from those
      expected to arise from a simple Poisson distribution of centers, and we discuss
      the implications of this finding in terms of nucleated and spinodal dewetting.
      Variations in both the surface roughness and the in-plane correlation length have
      been followed as a function of annealing time to probe the surface dewetting
      dynamics. SR valence band photoemission illustrates that the highest occupied
      molecular orbital (HOMO) of the cluster is found 2 eV below the Fermi level. Fe
      2p --> 3d and Sn 3d --> 5p resonant photoemission spectroscopy have been used to
      enhance the cross sections of the partial density of states associated with the
      Fe and Sn atoms. Sn atoms make a large contribution to the HOMO of the cluster,
      whereas the Fe atoms are associated with an electronic environment seemingly very
      similar to that in the "parent" ferrocene molecule.

PMID- 15248733
TI  - Effect of stamp deformation on the quality of microcontact printing: theory and
      experiment.
AB  - Microcontact printing (microCP) is an effective way to generate micrometer- or
      submicrometer-sized patterns on a variety of substrates. However, the fidelity of
      the final pattern depends critically on the coupled phenomena of stamp
      deformation, fluid transfer between surfaces, and the ability of the ink to self
      assemble on the substrate. In particular, stamp deformation can produce
      undesirable effects that limit the practice and precision of microCP.
      Experimental observations and comparison with theoretical predictions are
      presented here for three of the most undesirable consequences of stamp
      deformation: (1) roof collapse of low aspect ratio recesses, (2) buckling of high
      aspect ratio plates, and (3) lateral sticking of high aspect ratio plates. Stamp
      behavior was observed visually with an inverted optical microscope while load
      displacement data were collected during compression and retraction of stamps.
      Additionally, a "robotic stamper" was used to deliver ink patterns in precise
      locations on substrates. These monomolecular ink patterns were then observed in
      high contrast using the surface potential scanning mode of an atomic force
      microscope. Theoretical models based on continuum mechanics were used to
      accurately predict both physical deformation of the stamp and the resultant
      inking patterns. The close agreement between these models and the experimental
      data presented clearly demonstrates the essential considerations one must weigh
      when designing stamp geometry, material, and loading conditions for optimal
      pattern fidelity.

PMID- 15248734
TI  - Compaction and multiple chain assembly of DNA with the cationic polymer
      poly(aluminum chloride) (PAC).
AB  - Assembly of DNA molecules by the addition of poly(aluminum chloride) (PAC) was
      studied. In the absence of PAC, electron microscopy indicated the formation of
      elongated coiled DNA molecules. In the presence of PAC, multiple doughnut-like
      structures, 8-15 nm thick, formed and fused together. When salt was added, the
      doughnut-like structures tended to be thinner and the morphology of the fused
      doughnuts became irregular. We obtained a view of a single DNA structure by
      fluorescent microscopy, which revealed that individual DNA molecules undergo a
      discrete transition from an elongated to compacted state with an increase in PAC
      concentration. Electron microscopic observation showed that a regular doughnut is
      the typical structure seen under low salt conditions. At high salt
      concentrations, the doughnut shape deformed, yielding results similar to those
      produced by the salt effect on DNA assembly at high DNA concentrations.

PMID- 15248735
TI  - Particle morphology as a control of permeation in polymer films obtained from
      MMA/nBA colloidal dispersions.
AB  - The combination of precision-controlled weight loss measurements and
      spectroscopic surface FT-IR analysis allowed us to identify unique behaviors of
      poly(methyl methacrylate) (p-MMA). When MMA and n-butyl acrylate (nBA) are
      polymerized into p-MMA and p-nBA homopolymer blends, MMA/nBA random copolymers,
      and p-MMA/p-nBA core-shell morphologies, a controlled mobility and stratification
      of low molecular weight components occurs in films formed from coalesced
      colloidal dispersions. Due to different affinities toward water, p-MMA and p-nBA
      are capable of releasing water at different rates, depending upon particle
      morphological features of initial dispersions. As coalescence progresses, water
      molecules are released from the high free volume p-nBA particles, whereas p-MMA
      retains water molecules for the longest time due to its hydrophilic nature. As a
      result, water losses at extended coalescence times are relatively small for p
      MMA. MMA/nBA copolymer and p-MMA/p-nBA blends follow the same trends, although
      the magnitudes of changes are not as pronounced. The p-MMA/p-nBA core-shell
      behavior resembles that of p-nBA homopolymer, which is attributed to
      significantly lower content of the p-MMA component in particles. Annealing of
      coalesced colloidal films at elevated temperatures causes migration of SDOSS to
      the F-A interface, but for films containing primarily p-nBA, reverse diffusion
      back into the bulk is observed. These studies illustrate that the combination of
      different particle morphologies and temperatures leads to controllable permeation
      processes through polymeric films.

PMID- 15248736
TI  - Floc strength characterization technique. An insight into silica aggregation.
AB  - This paper tests an approach to the estimation of relative particle bond strength
      based on the nondimensional floc and aggregation factors. The strength of flocs
      formed by aggregating nanosized silica particles with the addition of potassium
      chloride (KCl) or cationic surfactants, alkyltrimethylammonium bromide (mixture
      of CTAB, DTAB, and MTAB) was analyzed. The bonding force of the flocs formed in
      surfactant compared to that formed in the KCl system was estimated using the new
      dimensional analysis approach. This force ratio was then compared to that
      obtained by atomic force microscopy.

PMID- 15248737
TI  - Binding of sodium dodecyl sulfate to linear and star homopolymers of the nonionic
      poly(methoxyhexa(ethylene glycol) methacrylate) and the polycation poly(2
      (dimethylamino)ethyl methacrylate): electromotive force, isothermal titration
      calorimetry, surface tension, and small-angle neutron scattering measurements.
AB  - We investigated the binding of sodium dodecyl sulfate (SDS) to various linear and
      star polymers of the nonionic methoxyhexa(ethylene glycol) methacrylate (PMHEGMA)
      and the ionic 2-(dimethylamino)ethyl methacrylate (PDMAEMA), the latter being a
      polycation at low pH. The dodecyl sulfate ion selective electrode (EMF),
      isothermal titration calorimetry (ITC), and surface tension (ST) were applied to
      gain detailed information about interactions. In all cases there is evidence of
      significant binding of SDS over an extensive SDS concentration range spanning
      from ca. 10(-6) to 0.1 mol dm(-3). At pH 3, the polymer PDMAEMA is a strong
      polycation and here the binding is dominated by electrostatic 1:1 charge
      neutralization with the anionic surfactant. At their natural pH of 8.6, PMHEGMA
      and PDMAEMA polymers are essentially nonionic and bind SDS in the form of polymer
      bound aggregates in the concentration range of ca. 1 x 10(-3) to 3 x 10(-2) mol
      dm(-3). All the polymers also bind SDS to a lesser extent at concentrations below
      1 x 10(-3) mol dm(-3) reaching as low as 10(-7) mol dm(-3). This low
      concentration binding process involves the polymer and nonassociated SDS
      monomers. As far as we are aware, this is the first example that such a low
      concentration noncooperative binding process could be observed in SDS/neutral
      polymer systems by EMF and ST. We also showed that the nonionic surfactant
      hexa(ethylene glycol) mono-n-dodecyl ether (C12EO6) and the cationic
      cetyltrimethylammonium bromide (C16TAB) interact with star PDMAEMA. We believe
      that the interaction of C12EO6 and CTAB is of similar noncooperative type as the
      first SDS binding process in the range from ca. 10(-5) to 0.3 x 10(-3) mol dm(
      3). At the high concentration binding limit Csat of SDS, the above polymers
      become fully saturated with bound SDS micelles. We applied small angle neutron
      scattering (SANS) to determine the structure and aggregation numbers of the star
      polymer/bound SDS micelles and calculated the stoichiometry of such
      supramolecular complexes. The SANS data on PDMAEMA star polymers in the presence
      of C12EO6 showed only a limited monomer binding in contrast to linear PDMAEMA,
      which showed monomer C12EO6 binding at low concentrations but micellar aggregates
      at 6 x 10(-3) mol dm(-3).

PMID- 15248738
TI  - Novel pearl-necklace porous CdS nanofiber templated by organogel.
AB  - A new cholesterol organogelator 4 was synthesized and its gelation property was
      evaluated. It was confirmed that 4 was an effective gelator for various organic
      solvents and could self-assemble into network fibers with a bilayer of folded
      conformation in some organic solvents. Moreover, organogelator 4 could act as a
      template for the synthesis of novel pearl-necklace porous CdS nanofibers. The
      transcription process of organogel fibers into CdS nanofibers was investigated,
      and it was found that Cd2+ ions were coated on the organogel fibers by the
      interaction with ester groups of 4, which might lead to the change of the
      arrangement of the organogelator and seemed to serve as nucleation sites for
      metalization. The further growth of CdS began with these nucleation sites along
      the organogel fibers. Meanwhile, parts of 4 free from organogel fibers have an
      effect on the formation of the CdS nanofibers consisting of the network and
      wormlike CdS particles.

PMID- 15248739
TI  - Hydrothermal routes to prepare nanocrystalline mesoporous SnO2 having high
      thermal stability.
AB  - We report simple hydrothermal routes to prepare thermally stable SnO2 particles
      having high specific surface areas and mesoporosity. The preparation method
      includes a new combination of synthetic processes: hydrolysis of tin(IV) chloride
      at 95 degrees C in the absence of alkaline solutions (aqueous NH3 or NaOH),
      formation of nanocrystalline SnO2, and subsequent hydrothermal treatments at
      temperatures between 100 and 200 degrees C. After annealing treatments of the
      hydrothermally treated SnO2 particles at 400 or 500 degrees C, their crystallite
      sizes remained smaller than 7.7 nm and their specific surface areas were still
      higher than 110 m2/g, indicative of the high thermal stability against particle
      growth and sintering. Furthermore, mesoporosity evolved with a relatively narrow
      pore size distribution typically in the range of 3.0-4.3 nm. The effects of the
      hydrothermal treatment were explained by uniformization of the particle size that
      was beneficial to the suppression of particle growth.

PMID- 15248740
TI  - Modeling mercury porosimetry using statistical mechanics.
AB  - We consider mercury porosimetry from the perspective of the statistical
      thermodynamics of penetration of a nonwetting liquid into a porous material under
      an external pressure. We apply density functional theory to a lattice gas model
      of the system and use this to compute intrusion/extrusion curves. We focus on the
      specific example of a Vycor glass and show that essential features of mercury
      porosimetry experiments can be modeled in this way. The lattice model exhibits a
      symmetry that provides a direct relationship between intrusion/extrusion curves
      for a nonwetting fluid and adsorption/desorption isotherms for a wetting fluid.
      This relationship clarifies the status of methods that are used for transforming
      mercury intrusion/extrusion curves into gas adsorption/desorption isotherms. We
      also use Monte Carlo simulations to investigate the nature of the intrusion and
      extrusion processes.

PMID- 15248741
TI  - Simple model for grafted polymer brushes.
AB  - The first theories of grafted polymer brushes assumed a step profile for the
      monomer density. Later, the real density profile was obtained from Monte Carlo or
      molecular dynamics simulations and calculated numerically using a self-consistent
      field theory. The analytical approximations of the solutions of the self
      consistent field equations provided a parabolic dependence of the self-consistent
      field, which in turn led to a parabolic distribution for the monomer density in
      neutral brushes. As shown by numerical simulations, this model is not accurate
      for dense polymer brushes, with highly stretched polymers. In addition, the
      scaling laws obtained from the analytical approximations of the self-consistent
      field theory are identical to those derived from the earlier step-profile
      approximation and predict a vanishing thickness of the brush at low graft
      densities, and a thickness exceeding the length of the polymer chains at high
      graft densities. Here a simple model is suggested to calculate the monomer
      density and the interaction between surfaces with grafted polymer brushes, based
      on an approximate calculation of the partition function of the polymer chains.
      The present model can be employed for both good and poor solvents, is compatible
      with a parabolic-like profile at moderate graft densities, and leads to an almost
      steplike density for highly stretched brushes. While the thickness of the brush
      depends strongly on solvent quality, it is a continuous function in the vicinity
      of the temperature. In good and moderately poor solvents, the interactions
      between surfaces with grafted polymer brushes are always repulsive, whereas in
      poor solvents the interactions are repulsive at small separations and become
      attractive at intermediate separation distances, in agreement with experiment. At
      large separations, a very weak repulsion is predicted.

PMID- 15248742
TI  - Heat-stabilized glycosphingolipid films for biosensing applications.
AB  - We have investigated a means of producing thin, oriented lipid monolayers which
      are stable under repeated washing and which may be useful in biosensing or
      surface-coating applications. Phosphatidylcholine and the glycosphingolipid GM1
      were used as representative lipids for this work. Initially, a mixed self
      assembled monolayer of octanethiol and hexadecanethiol was produced on a gold
      surface. This hydrophobic monolayer was then brought into contact with a thin
      lipid film that had been assembled at the liquid/air interface of a solution,
      allowing the lipid to deposit on the gold surface through hydrophobic
      interactions. The lipid layer was then heated to cause intermingling of the fatty
      acid and alkanethiol chains and cooled to form a highly stable film which
      withstood repeated rinsing and solution exposure. Presence and stability of the
      film were confirmed via ellipsometry, Fourier transform infrared spectroscopy,
      and quartz crystal microbalance (QCM), with an average overall film thickness of
      approximately 3.5 nm. This method was then utilized to produce GM1 layers on gold
      coated QCM crystals for affinity sensing trials with cholera toxin. For these
      sensing elements, the lower detection limit of cholera toxin was found to be
      approximately 0.5 microg/mL, with a logarithmic relationship between toxin
      concentration and frequency response spanning over several orders of magnitude.
      Potential sites for nonspecific adsorption were blocked using serum albumin
      without sacrificing toxin specificity.

PMID- 15248743
TI  - Monte Carlo models for nanoparticle formation in two microemulsion systems.
AB  - The process of formation of nanoparticles obtained by mixing two micellized,
      aqueous solutions has been simulated using the Monte Carlo technique. The model
      includes the phenomena of finite reaction, nucleation, and growth via
      intermicellar exchange. This exploratory study examines the characteristic
      particle size distributions (PSDs) that result from using combinations of
      different initial reactant distributions (Poissonian and geometric) and different
      types of intermicellar exchange protocols (random, cooperative, and binomial). It
      is observed that the PSDs obtained using an initial Poissonian distribution of
      reactants and random exchange rules are similar to reported experimental results
      for CdS nanoparticles. The effect of exchange efficiency and reaction rate has
      also been studied. It is seen that a high exchange efficiency leads to relatively
      larger particle sizes. Also, a slow reaction rate has been shown to lead to the
      formation of larger nanoparticles.

PMID- 15248744
TI  - Application of metalloporphyrins in nanocrystalline dye-sensitized solar cells
      for conversion of sunlight into electricity.

PMID- 15248745
TI  - Shear-induced mesophase organization of polyanionic rigid rods in aqueous
      solution.

PMID- 15248746
TI  - Following ligand binding and ligand reactions in proteins via Raman
      crystallography.
AB  - Raman crystallography permits the monitoring of chemical events in single-protein
      crystals in real time. Using a Raman microscope, it is possible to obtain protein
      Raman spectroscopic data of unprecedented quality and stability. The latter
      features allow us to obtain the Raman spectrum for small molecules soaking into
      crystals under normal (nonresonance) Raman conditions. Thus, via an approach
      utilizing Raman difference spectroscopy, we can quantitate the amount of ligand
      in the crystal, determine the chemistry of inhibitor-protein interactions, and
      follow chemical reactions in the active site on the time scale of minutes. While
      providing unique chemical insights, these data also provide an invaluable guide
      for determining the conditions for flash-freezing crystals for X-ray
      crystallographic analysis. In addition, the Raman difference spectra often
      contain contributions from protein modes due to protein conformational changes
      occurring upon ligand binding. These features allow us to probe events ranging
      from small cooperative conformational changes to massive and unexpected secondary
      structure changes in the crystal. An experimental advantage of Raman
      crystallography is that the data can be collected from crystals in situ, in
      sitting or hanging drops, under the conditions used to grow the crystals.

PMID- 15248747
TI  - Structural characterization of the stringent response related
      exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family.
AB  - Exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes
      play central roles in the bacterial stringent response induced by starvation. The
      high-resolution crystal structure of the putative Aquifex aeolicus PPX/GPPA
      phosphatase from the actin-like ATPase domain superfamily has been determined,
      providing the first insights to features of the common catalytic core of the
      PPX/GPPA family. The protein has a two-domain structure with an active site
      located in the interdomain cleft. Two crystal forms were investigated (type I and
      II) at resolutions of 1.53 and 2.15 A, respectively. This revealed a structural
      flexibility that has previously been described as a "butterfly-like" cleft
      opening around the active site in other actin-like superfamily proteins. A
      calcium ion is observed at the center of this region in type I crystals,
      substantiating that PPX/GPPA enzymes use metal ions for catalysis. Structural
      analysis suggests that nucleotides bind at a similar position to that seen in
      other members of the superfamily.

PMID- 15248748
TI  - Interplay between site-specific mutations and cyclic nucleotides in modulating
      DNA recognition by Escherichia coli cyclic AMP receptor protein.
AB  - Mutagenesis of various amino acids in Escherichia coli cyclic AMP receptor
      protein (CRP) has been shown to modulate protein compressibility and dynamics
      [Gekko et al. (2004) Biochemistry 43, 3844-3852]. Cooperativity of cAMP binding
      to CRP and the apparent DNA binding affinity are perturbed [Lin and Lee (2002)
      Biochemistry 41, 11857-11867]. The aim of this study is to explore the effects of
      mutation on the surface chemistry of CRP and to define the consequences of these
      changes in affecting specific DNA sequence recognition by CRP. Furthermore, the
      role of the interplay between mutation and specific identity of the bound cyclic
      nucleotide in this DNA recognition was explored. In the current study, effects of
      eight site-specific mutations (K52N, D53H, S62F, T127L, G141Q, L148R, H159L, and
      K52N/H159L) on DNA recognition of four sequences (Class I (site PI of lac), Class
      II (site PI of gal), and synthetic sequences that are hybrids of Classes I and II
      sites) modulated by three different cyclic nucleotides (cAMP, cCMP, and cGMP)
      were investigated. All mutations altered the surface chemistry of CRP as
      evidenced by the change in elution properties of these proteins from different
      matrixes. While T127L, S62F, K52N, and H159L exhibited unexpected behavior under
      combinations of specific experimental conditions, such as the identity of bound
      cyclic nucleotide and DNA sequence, in general, results showed that the
      affinities of CRP for DNA were sequence-dependent, increasing in the order of
      lacgal26 < gal26 < lac26 < gallac26 for all the mutants in the presence of 200
      microM cAMP. The apparent association constants significantly increased in the
      order of no cyclic nucleotide approximately cGMP < cCMP < cAMP for all the
      examined DNA sequences. Linear correlation between the DeltaG for CRP-DNA complex
      formation and the cooperativity energy for cAMP binding was observed with
      gallac26, gal26, and lacgal26; however, the slope of this linear correlation is
      DNA sequence dependent. Structural information was presented to rationalize the
      interplay between CRP sequence and cyclic nucleotides in defining the recognition
      of DNA sequences.

PMID- 15248749
TI  - Dynamic characterization of a DNA repair enzyme: NMR studies of [methyl
      13C]methionine-labeled DNA polymerase beta.
AB  - Crystallographic characterization of DNA polymerase beta (pol beta) has suggested
      that multiple-domain and subdomain motions occur during substrate binding and
      catalysis. NMR studies of [methyl-(13)C]methionine-labeled pol beta were
      conducted to characterize the structural and dynamic response to ligand binding.
      The enzyme contains seven methionine residues, one of which is at the amino
      terminus and is partially removed by the expression system. Three of the methyl
      resonances were readily assigned using site-directed mutants. Assignment of the
      resonances of Met155, Met158, and Met191 was more difficult due to the spatial
      proximity of these residues, so that assignments were based on NOESY-HSQC data
      and on the response to paramagnetic Co(2+) addition, as well as shift
      perturbations observed for the site-directed mutants. The response of the methyl
      resonances to substrate binding was evaluated by the serial addition of a
      template oligonucleotide, a downstream 5'-phosphorylated oligonucleotide, and a
      primer oligonucleotide to create a two-nucleotide-gapped DNA substrate. Addition
      of the single-stranded template DNA resulted in selective broadening of the
      methyl resonance of Met18 in the 8 kDa lyase domain, and this resonance then
      shifted and sharpened upon addition of a 5'-phosphate-terminated downstream
      complementary oligonucleotide. Conversion of the two-nucleotide-gapped DNA
      substrate to a single-nucleotide-gapped substrate by incorporation of ddCMP
      produced a small perturbation of the Met236 resonance, which makes contact with
      the primer strand in the crystal structure. The addition of a second equivalent
      of ddCTP to form the pol beta-DNA-ddCTP ternary complex resulted in significant
      shifts for the resonances corresponding to Met155, Met191, Met236, and Met282.
      The Met155 methyl resonance is severely broadened, while the Met191 and Met282
      resonances exhibit significant but less extreme broadening. Since only Met236
      makes contact with the substrate, the effects on Met155, Met236, and Met282
      result from indirect conformational and dynamic perturbations. Previous
      crystallographic characterization of this abortive complex indicated that a
      polymerase subdomain or segment (alpha-helix N) repositions itself to form one
      face of the binding pocket for the nascent base pair. Met282 serves as a probe
      for motion in this segment. Addition of Mg(2+)-dATP to pol beta in the absence of
      DNA produced qualitatively similar but much smaller effects on Met191 and Met155,
      but did not strongly perturb Met282, leading to the conclusion that Mg(2+)-dATP
      alone is insufficient to produce the large conformational changes that are
      observed in the abortive complex involving the gapped DNA with a blocked primer
      and ddNTP. Thus, the NMR data indicate that the nucleotide-DNA interaction
      appears to be essential for conformational activation.

PMID- 15248750
TI  - Pattern of 4-thiouridine-induced cross-linking in 16S ribosomal RNA in the
      Escherichia coli 30S subunit.
AB  - The locations of RNA-RNA cross-links in 16S rRNA were determined after in vivo
      incorporation of 4-thiouridine (s(4)U) into RNA in a strain of Escherichia coli
      deficient in pyrimidine synthesis and irradiation at >320 nm. This was done as an
      effort to find RNA cross-links different from UVB-induced cross-links that would
      be valuable for monitoring the 30S subunit in functional complexes. Cross-linked
      16S rRNA was separated on the basis of loop size, and cross-linking sites were
      identified by reverse transcription, RNase H cleavage, and RNA sequencing. A
      limited number of RNA-RNA cross-links in nine regions were observed. In five
      regions-s(4)U562 x C879-U884, s(4)U793 x A1519, s(4)U1189 x U1060-G1064,
      s(4)U1183 x A1092, and s(4)U991 x C1210-U1212-the s(4)U-induced cross-links are
      similar to UVB-induced cross-links observed previously. In four other regions
      s(4)U960 x A1225, s(4)U820 x G570, s(4)U367 x A55-U56, and s(4)U239 x A120-the
      s(4)U-induced cross-links are different from UVB-induced cross-links. The pattern
      of cross-linking is not limited by the distribution of s(4)U, because there are
      at least 112 s(4)U substitution sites in the 16S rRNA. The relatively small
      number of s(4)U-mediated cross-links is probably determined by the organization
      of the RNA in the 30S subunit, which allows RNA conformational flexibility needed
      for cross-link formation in just a limited region.

PMID- 15248751
TI  - Magnesium dependence of the amplified conformational switch in the trans-acting
      hepatitis delta virus ribozyme.
AB  - The ability of divalent metal ions to participate in both structure formation and
      catalytic chemistry of RNA enzymes (ribozymes) has made it difficult to separate
      their cause and effect in ribozyme function. For example, the recently solved
      crystal structures of precursor and product forms of the cis-cleaving genomic
      hepatitis delta virus (HDV) ribozyme show a divalent metal ion bound in the
      active site that is released upon catalysis due to an RNA conformational change.
      This conformational switch is associated with a repositioning of the
      catalytically involved base C75 in the active-site cleft, thus controlling
      catalysis. These findings confirm previous data from fluorescence resonance
      energy transfer (FRET) on a trans-acting form of the HDV ribozyme that found a
      global conformational change to accompany catalysis. Here, we further test the
      conformational switch model by measuring the Mg(2+) dependence of the global
      conformational change of the trans-acting HDV ribozyme, using circular dichroism
      and time-resolved FRET as complementary probes of secondary and tertiary
      structure formation, respectively. We observe significant differences in both
      structure and Mg(2+) affinity of the precursor and product forms, in the presence
      and absence of 300 mM Na(+) background. The precursor shortens while the product
      extends with increasing Mg(2+) concentration, essentially amplifying the
      structural differences observed in the crystal structures. In addition, the
      precursor has an approximately 2-fold and approximately 13-fold lower Mg(2+)
      affinity than the product in secondary and tertiary structure formation,
      respectively. We also have compared the C75 wild-type with the catalytically
      inactive C75U mutant and find significant differences in global structure and
      Mg(2+) affinity for both their precursor and product forms. Significantly, the
      Mg(2+) affinity of the C75 wild-type is 1.7-2.1-fold lower than that of the C75U
      mutant, in accord with the notion that C75 is essential for a catalytic
      conformational change that leads to a decrease in the local divalent metal ion
      affinity and release of a catalytic metal. Thus, a consistent picture emerges in
      which divalent metal ions and RNA functional groups are intimately intertwined in
      affecting structural dynamics and catalysis in the HDV ribozyme.

PMID- 15248752
TI  - Mutational analysis of peptidyl carrier protein and acyl carrier protein synthase
      unveils residues involved in protein-protein recognition.
AB  - 4'-Phosphopantetheinyl transferases (PPTases) are essential for the production of
      fatty acids by fatty acid synthases (primary metabolism) and natural products by
      nonribosomal peptide synthetases and polyketide synthases (secondary metabolism).
      These systems contain carrier proteins (CPs) for the covalent binding of reaction
      intermediates during synthesis. PPTases transfer the 4'-phosphopantetheine moiety
      from coenzyme A (CoA) onto conserved serine residues of the apo-CPs to convert
      them to their functionally active holo form. In bacteria, two types of PPTases
      exist that are evolutionary related but differ in their substrate spectrum. Acyl
      carrier protein synthases (AcpSs) recognize CPs from primary metabolism, whereas
      Sfp- (surfactin production-) type PPTases have a preference for CPs of secondary
      metabolism. Previous investigations showed that a peptidyl carrier protein (PCP)
      of secondary metabolism can be altered to serve as substrate for AcpS. We
      demonstrate here that a single mutation in PCP suffices for the modification of
      this CP by AcpS, and we have identified by mutational analysis several other PCP
      residues and two AcpS residues involved in substrate discrimination by this
      PPTase. These altered PCPs were still capable of serving their designated
      function in NRPS modules, and selective use of AcpS or Sfp leads to production of
      two different products by a trimodular NRPS.

PMID- 15248753
TI  - Alanine-scanning mutagenesis reveals a cytosine deaminase mutant with altered
      substrate preference.
AB  - Suicide gene therapy of cancer is a method whereby cancerous tumors can be
      selectively eradicated while sparing damage to normal tissue. This is
      accomplished by delivering a gene, encoding an enzyme capable of specifically
      converting a nontoxic prodrug into a cytotoxin, to cancer cells followed by
      prodrug administration. The Escherichia coli gene, codA, encodes cytosine
      deaminase and is introduced into cancer cells followed by administration of the
      prodrug 5-fluorocytosine (5-FC). Cytosine deaminase converts 5-FC into cytotoxic
      5-fluorouracil, which leads to tumor-cell eradication. One limitation of this
      enzyme/prodrug combination is that 5-FC is a poor substrate for bacterial
      cytosine deaminase. The crystal structure of bacterial cytosine deaminase (bCD)
      reveals that a loop structure in the active site pocket of wild-type bCD
      comprising residues 310-320 undergoes a conformational change upon cytosine
      binding, making several contacts to the pyrimidine ring. Alanine-scanning
      mutagenesis was used to investigate the structure-function relationship of amino
      acid residues within this region, especially with regard to substrate
      specificity. Using an E. coli genetic complementation system, seven active
      mutants were identified (F310A, G311A, H312A, D314A, V315A, F316A, and P318A).
      Further characterization of these mutants reveals that mutant F316A is 14-fold
      more efficient than the wild-type at deaminating cytosine to uracil. The mutant
      D314A enzyme demonstrates a dramatic decrease in cytosine activity (17-fold) as
      well as a slight increase in activity toward 5-FC (2-fold), indicating that
      mutant D314A prefers the prodrug over cytosine by almost 20-fold, suggesting that
      it may be a superior suicide gene.

PMID- 15248754
TI  - Intra-allelic suppression of a mutation that stabilizes microtubules and confers
      resistance to colcemid.
AB  - Cmd 4 is a colcemid resistant beta-tubulin mutant of Chinese hamster ovary cells
      that exhibits hypersensitivity to paclitaxel and temperature sensitivity for
      growth. The mutant beta-tubulin allele in this cell line encodes a D45Y amino
      acid substitution that produces colcemid resistance by making microtubules more
      stable. By selecting revertants of the temperature sensitive and paclitaxel
      hypersensitive phenotypes, we have identified three cis-acting suppressors of
      D45Y. One suppressor, V60A, maps to the same region as the D45Y alteration, and a
      second suppressor, Q292H, maps to a distant location. Both appear to produce
      compensatory changes in microtubule assembly that counteract the effects of the
      original D45Y substitution. Consistent with this view, expression of the V60A
      mutation in transfected wild-type cells produced paclitaxel resistance and
      greatly decreased microtubule assembly. Additionally, it produced a paclitaxel
      dependent phenotype in which cells grew normally in the presence, but not the
      absence, of the drug. The Q292H mutation caused even greater disassembly of
      microtubules such that cells were unable to proliferate when the transgene was
      expressed; but, unlike the V60A mutation, cell growth could not be rescued by
      paclitaxel. A third suppressor, A254V, maps to a region near the interface
      between alpha- and beta-tubulin that contains the colchicine binding site.
      Although it made transfected wild-type cells hypersensitive to colcemid, it did
      not affect paclitaxel or vinblastine sensitivity, nor did it reduce microtubule
      assembly. We suggest that this mutation acts by increasing tubulin's affinity for
      colcemid.

PMID- 15248755
TI  - Clusters of transmembrane residues are critical for human prostacyclin receptor
      activation.
AB  - Relaxation of vascular smooth muscle and prevention of blood coagulation are
      mediated by ligand-induced activation of the human prostacyclin (hIP) receptor, a
      seven-transmembrane-domain G-protein-coupled receptor (GPCR). In this study, we
      elucidate the molecular requirements for receptor activation within the region of
      the ligand-binding pocket, identifying transmembrane residues affecting potency.
      Eleven of 30 mutated residues in the region of the ligand-binding domain
      exhibited defective activation (decreased potency). These critical residues
      localized to four distinct clusters (analysis via a rhodopsin-based human
      prostacyclin receptor homology model). Residues Y75(2.65) (TMII), F95(3.28)
      (TMIII), and R279(7.40) (TMVII) comprised the immediate binding-pocket cluster
      and were shown to be essential for proper receptor activation, compared to
      equivalent expression levels of the wild-type hIP (WT EC(50) = 1.2 +/- 0.1 nM;
      Y75(2.65)A EC(50) = 347.3 +/- 62.8 nM, p < 0.001; F95(3.28)A EC(50) = 8.0 +/- 0.6
      nM, p < 0.001; R279(7.40)A EC(50) = 130 +/- 63.0 nM, p < 0.001). Residues
      S20(1.39) (TMI), F24(1.43) (TMI), and F72(2.62) (TMII) were localized to a
      cluster involving P17(1.36), a critical residue thought to facilitate
      transmembrane movement during changes in activation conformation. A third cluster
      formed around amino acid D60(2.50) (TMII), containing the highly conserved (100%
      of prostanoid receptors) D288(7.49)/P289(7.50) motif located in TMVII. Last, a
      large hydrophobic cluster composed of aromatic residues F146(4.52) (TMIV),
      F150(4.56) (TMIV), F184(5.40) (TMV), and Y188(5.44) (TMV) was observed away from
      the ligand-binding pocket, but still necessary for hIP activation. These results
      assist in delineating the potential molecular requirements for agonist-induced
      signaling through the transmembrane domain. Such observations may be generally
      applicable, as many of these clusters are highly conserved among the prostanoid
      receptors as well as other class A GPCRs.

PMID- 15248756
TI  - Inhibitor coordination interactions in the binuclear manganese cluster of
      arginase.
AB  - Arginase is a manganese metalloenzyme that catalyzes the hydrolysis of L-arginine
      to form L-ornithine and urea. The structure and stability of the binuclear
      manganese cluster are critical for catalytic activity as it activates the
      catalytic nucleophile, metal-bridging hydroxide ion, and stabilizes the
      tetrahedral intermediate and its flanking states. Here, we report X-ray
      structures of a series of inhibitors bound to the active site of arginase, and
      each inhibitor exploits a different mode of coordination with the Mn(2+)(2)
      cluster. Specifically, we have studied the binding of fluoride ion (F(-); an
      uncompetitive inhibitor) and L-arginine, L-valine, dinor-N(omega)-hydroxy-L
      arginine, descarboxy-nor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6
      boronohexanoic acid. Some inhibitors, such as fluoride ion, dinor-N(omega)
      hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid, cause the net
      addition of one ligand to the Mn(2+)(2) cluster. Other inhibitors, such as
      descarboxy-nor-N(omega)-hydroxy-L-arginine, simply displace the metal-bridging
      hydroxide ion of the native enzyme and do not cause any net change in the metal
      coordination polyhedra. The highest affinity inhibitors displace the metal
      bridging hydroxide ion (and sometimes occupy a Mn(2+)(A) site found vacant in the
      native enzyme) and maintain a conserved array of hydrogen bonds with their alpha
      amino and -carboxylate groups.

PMID- 15248757
TI  - Crystallographic analysis reveals that anticancer clinical candidate L-778,123
      inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different
      binding modes.
AB  - Many signal transduction proteins that control growth, differentiation, and
      transformation, including Ras GTPase family members, require the covalent
      attachment of a lipid group by protein farnesyltransferase (FTase) or protein
      geranylgeranyltransferase type-I (GGTase-I) for proper function and for the
      transforming activity of oncogenic mutants. FTase inhibitors are a new class of
      potential cancer therapeutics under evaluation in human clinical trials. Here, we
      present crystal structures of the clinical candidate L-778,123 complexed with
      mammalian FTase and complexed with the related GGTase-I enzyme. Although FTase
      and GGTase-I have very similar active sites, L-778,123 adopts different binding
      modes in the two enzymes; in FTase, L-778,123 is competitive with the protein
      substrate, whereas in GGTase-I, L-778,123 is competitive with the lipid substrate
      and inhibitor binding is synergized by tetrahedral anions. A comparison of these
      complexes reveals that small differences in protein structure can dramatically
      affect inhibitor binding and selectivity. These structures should facilitate the
      design of more specific inhibitors toward FTase or GGTase-I. Finally, the binding
      of a drug and anion together could be applicable for developing new classes of
      inhibitors.

PMID- 15248758
TI  - Dynamic relationships among type IIa bacteriocins: temperature effects on
      antimicrobial activity and on structure of the C-terminal amphipathic alpha helix
      as a receptor-binding region.
AB  - Dynamic aspects of structural relationships among class IIa bacteriocins, which
      are antimicrobial peptides from lactic acid bacteria (LAB), have been examined by
      use of circular dichroism (CD), molecular dynamics (MD) simulations, and activity
      testing. Pediocin PA-1 is a potent class IIa bacteriocin, which contains a second
      C-terminal disulfide bond in addition to the highly conserved N-terminal
      disulfide bond. A mutant of pediocin PA-1, ped[M31Nle], wherein the replacement
      of methionine by norleucine (Nle) gives enhanced stability toward aerobic
      oxidation, was synthesized by solid-phase peptide synthesis to study the activity
      of the peptide in relation to its structure. The secondary structural analysis
      from CD spectra of ped[M31Nle], carnobacteriocin B2 (cbn B2), and leucocin A
      (leuA) at different temperatures suggests that the alpha-helical region of these
      peptides is important for target recognition and activity. Using molecular
      modeling and dynamic simulations, complete models of pediocin PA-1, enterocin P,
      sakacin P, and curvacin A in 2,2,2-trifluoroethanol (TFE) were generated to
      compare structural relationships among this class of bacteriocins. Their high
      sequence similarity allows for the use of homology modeling techniques. Starting
      from homology models based on solution structures of leuA (PDB code 1CW6) and
      cbnB2 (PDB code 1CW5), results of 2-4 ns MD simulations in TFE and water at 298
      and 313 K are reported. The results indicate that these peptides have a common
      helical C-terminal domain in TFE but a more variable beta sheet or coiled N
      terminus. At elevated temperatures, pediocin PA-1 maintains its overall
      structure, whereas peptides without the second C-terminal disulfide bond, such as
      enterocin P, sakacin P, curvacin A, leuA, and cbnB2 experience partial disruption
      of the helical section. Pediocin PA-1 and ped[M31Nle] were found to be equally
      active at different temperatures, whereas the other peptides that lack the second
      C-terminal disulfide bond are 30-50 times less antimicrobially potent at 310 K
      (37 degrees C) than at 298 K (25 degrees C). These results indicate that the
      structural changes in the helical region observed at elevated temperatures
      account for the loss of activity of these peptides. The presence of C-terminal
      hydrophobic residues on one side of the amphipathic helix in class IIa
      bacteriocins is an important feature for receptor recognition and specificity
      toward particular organisms. This study assists in the understanding of structure
      activity relationships in type IIa bacteriocins and demonstrates the importance
      of the conserved C-terminal amphipathic alpha helix for activity.

PMID- 15248759
TI  - Endothelin receptor in virus-like particles: ligand binding observed by
      fluorescence fluctuation spectroscopy.
AB  - The functional analysis of transmembrane receptor proteins is frequently hampered
      by the difficulty to produce sufficiently homogeneous receptor preparations that
      preserve the physiological biomembrane integration of the receptor protein. To
      improve the receptor protein density in the lipid bilayer and to maintain the
      physiological lipid-protein environment, a novel method has been established that
      enables the selective integration of transmembrane receptors into a virus-like
      particle (VLiP). Here we have studied the binding of tetramethylrhodamine-labeled
      endothelin-1 (TMR-ET-1) to VLiP-integrated endothelin A receptor (ET(A)R) by
      fluorescence fluctuation spectroscopy. The concentration of TMR-ET-1 was
      determined by fluorescence correlation spectroscopy (FCS). These measurements
      also confirmed that the free ligand is monomeric in solution in our experiments.
      Fluorescence intensity distribution analysis (FIDA) was used to quantify the
      fraction of ligands bound to ET(A)Rs in the VLiPs. For the interaction between ET
      1 and VLiP-integrated ET(A)Rs, K(D) values of 0.5 nM and 0.3 nM were determined
      from ligand and receptor titration experiments, respectively. For comparison, a
      FIDA analysis was also carried out with ET(A)Rs in membrane fragments derived
      from an ET(A)R-overexpressing mammalian cell line, which yielded a similar K(D)
      of 0.2 nM. In addition, we examined the binding competition of a set of reference
      compounds to VLiP-ET(A)Rs in the presence of ET-1 and obtained K(i) values
      similar to those reported in the literature. Our results demonstrate that
      integration into VLiPs does not change the binding properties of the ET(A)Rs.
      FIDA analysis of VLiP-integrated receptors shows great promise for highly
      miniaturized and fast compound testing in the pharmaceutical industry.

PMID- 15248760
TI  - CO-induced structural rearrangement of the C cluster in Carboxydothermus
      hydrogenoformans CO dehydrogenase-evidence from Ni K-edge X-ray absorption
      spectroscopy.
AB  - We have examined the C cluster in type II CO dehydrogenase (CODH) from
      Carboxydothermus hydrogenformans using Ni K-edge X-ray absorption near edge
      spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy.
      The enzyme was studied under three conditions: "as-isolated" and after treatment
      with CO or Ti(III). The shape of the Ni K-edge changes slightly between the
      different conditions, but no significant edge shift is seen, suggesting that the
      C cluster contains Ni(II) in both forms. The Ni EXAFS of as-isolated CODH can be
      simulated with 4 Ni-S interactions at 2.20 A with a large spread in distances. A
      light atom (C, N, O) is not required to fit the spectrum. After CO treatment,
      significant changes are observed in the EXAFS. A new feature appears at
      approximately 2.7 A; this component is consistent with a Ni-Fe interaction. The
      average Ni-S distance also expands to approximately 2.25 A. The changes between
      the two forms suggest that the active site (C cluster) undergoes structural
      rearrangement after CO treatment, and the observed changes help reconcile the two
      different crystal structures. The implications of the structural change for the
      enzyme activation and mechanism are discussed.

PMID- 15248761
TI  - Hierarchical map of protein unfolding and refolding at thermal equilibrium
      revealed by wide-angle X-ray scattering.
AB  - Hierarchical features of the thermal unfolding-refolding structural transition of
      hen egg white lysozyme (HEWL) have been studied in the temperature range from 13
      to 84 degrees C by using high-resolution wide-angle X-ray scattering (WAXS)
      measurements at a third-generation synchrotron source. We have gathered high
      statistic WAXS data of the reversible unfolding-refolding process of HEWL in the
      q range from approximately 0.05 to approximately 3 A(-1) [q = (4pi/lambda)
      sin(theta/2), where theta is the scattering angle and lambda the wavelength].
      This measured q range corresponds to the spatial distance from approximately 2 to
      approximately 125 A, which covers all hierarchical structures of a small globular
      protein such as HEWL, namely, tertiary, domain, and secondary structures. Because
      of this, we have found that the pH dependence of the thermal structural
      transition of HEWL is well characterized by the various hierarchical levels and
      the transition concurrence among them. In this report, we present a new
      hierarchical map depiction of unfolding-refolding transitions. Using scattering
      with various ranges of q values, we determine the molar ratio of native-like
      protein structure defined by the data in each range, thus producing a map of the
      amount of native-like structure as a function of the hierarchical level or
      resolution. This map can visualize a detailed feature of the unfolding-refolding
      transition of a protein depending on various structural hierarchical levels;
      however, the exact meaning of the map will await sharpening by additional works.

PMID- 15248762
TI  - Computer modeling of polyleucine-based coiled coil dimers in a realistic membrane
      environment: insight into helix-helix interactions in membrane proteins.
AB  - Simulated annealing was performed to model parallel dimers of alpha-helical
      transmembrane peptides with the sequence L(11)XL(12), predicting left-handed
      coiled coil geometry in all cases. Insertion of peptides containing threonine,
      asparagine, alanine, phenylalanine, and leucine in position 12 into realistic
      model membranes showed these structures were stable for 20 ns of molecular
      dynamics simulation time. Threonine could participate in intermolecular hydrogen
      bonds, but predominantly formed hydrogen bonds to the backbone of the helix it
      resided on. These hydrogen bonds, although infrequent, appeared to promote closer
      association of polyleucine helices. Asparagine participated in multiple, rapidly
      fluctuating intermolecular and intramolecular hydrogen bonds, and may have
      slightly destabilized optimum van der Waals packing in favor of optimum hydrogen
      bonding. Coordinated rotations of transmembrane helices about their axes were
      observed, indicating helices may rotate around one another during the folding of
      membrane proteins or other processes. These rotations were inhibited by
      phenylalanine, suggesting a role for bulky residues in modulating membrane
      protein dynamics.

PMID- 15248763
TI  - Residues within transmembrane domains 4 and 6 of the Na,K-ATPase alpha subunit
      are important for Na+ selectivity.
AB  - The Na,K- and H,K-ATPases are plasma membrane enzymes responsible for the active
      exchange of extracellular K(+) for cytoplasmic Na(+) or H(+), respectively. At
      present, the structural determinants for the specific function of these ATPases
      remain poorly understood. To investigate the cation selectivity of these ATPases,
      we constructed a series of Na,K-ATPase mutants in which residues in the membrane
      spanning segments of the alpha subunit were changed to the corresponding residues
      common to gastric H,K-ATPases. Thus, mutants were created with substitutions in
      transmembrane domains TM1, TM4, TM5, TM6, TM7, and TM8 independently or together
      (designated TMAll). The function of each mutant was assessed after coexpression
      with the beta subunit in Sf-9 cells using baculoviruses. The enzymatic properties
      of TM1, TM7, and TM8 mutants were similar to the wild-type Na,K-ATPase, and while
      TM5 showed modest changes in apparent affinity for Na(+), TM4, TM6, and TMAll
      displayed an abnormal activity. This resulted in a Na(+)-independent hydrolysis
      of ATP, a 2-fold higher K(0.5) for Na(+) activation, and the ability to function
      at low pH. These results suggest a loss of discrimination for Na(+) over H(+) for
      the enzymes. In addition, TM4, TM6, and TMAll mutants exhibited a 1.5-fold lower
      affinity for K(+) and a 4-5-fold decreased sensitivity to vanadate. Altogether,
      these results provide evidence that residues in transmembrane domains 4 and 6 of
      the alpha subunit of the Na,K-ATPase play an important role in determining the
      specific cation selectivity of the enzyme and also its E1/E2 conformational
      equilibrium.

PMID- 15248764
TI  - Structural changes in the photoactive site of proteorhodopsin during the primary
      photoreaction.
AB  - Proteorhodopsin (PR), found in marine gamma-proteobacteria, is a newly discovered
      light-driven proton pump similar to bacteriorhodopsin (BR). Because of the
      widespread distribution of proteobacteria in the worldwide oceanic waters, this
      pigment may contribute significantly to the global solar energy input in the
      biosphere. We examined structural changes that occur during the primary
      photoreaction (PR --> K) of wild-type pigment and two mutants using low
      temperature FTIR difference spectroscopy. Several vibrations detected in the 3500
      3700 cm(-1) region are assigned on the basis of H(2)O --> H(2)(18)O exchange to
      the perturbation of one or more internal water molecules. Substitution of the
      negatively charged Schiff base counterion, Asp97, with the neutral asparagine
      caused a downshift of the ethylenic (C=C) and Schiff base (C=N) stretching modes,
      in agreement with the 27 nm red shift of the visible lambda(max). However, this
      replacement did not alter the normal all-trans to 13-cis isomerization of the
      chromophore or the environment of the detected water molecule(s). In contrast,
      substitution of Asn230, which is in a position to interact with the Schiff base,
      with Ala induces a 5 nm red shift of the visible lambda(max) and alters the PR
      chromophore structure, its isomerization to K, and the environment of the
      detected internal water molecules. The combination of FTIR and site-directed
      mutagenesis establishes that both Asp97 and Asn230 are perturbed during the
      primary phototransition. The environment of Asn230 is further altered during the
      thermal decay of K. These results suggest that significant differences exist in
      the conformational changes which occur in the photoactive sites of
      proteorhodopsin and bacteriorhodopsin during the primary photoreaction.

PMID- 15248765
TI  - Herpes simplex virus-1 primase: a polymerase with extraordinarily low fidelity.
AB  - We utilized templates of defined sequence to investigate the fidelity and
      mechanism of NTP misincorporation by DNA primase from herpes simplex virus-1.
      Herpes primase generated a wide range of mismatches during primer synthesis,
      including purine-purine, pyrimidine-pyrimidine, and purine-pyrimidine mismatches,
      and could even polymerize consecutive incorrect NTPs. Polymerization of
      noncognate NTPs resulted from primase misreading the template, as opposed to a
      primer slippage or dislocation mutagenesis mechanism. Primase did not efficiently
      misincorporate NTPs during the initiation reaction (i.e., dinucleotide
      synthesis). However, during primer elongation (after dinucleotide formation),
      herpes primase was extraordinarily inaccurate. It misincorporated NTPs at
      frequencies as high as 1 in 7, although frequencies of 1 in 25 to 1 in 60 were
      more common. In every case, however, misincorporation frequencies were no less
      than 1 in 100. For a specific mismatch, the DNA sequences flanking the site where
      misincorporation occurred could influence the frequency of misincorporation. This
      remarkably low level of fidelity is as low as that observed for the least
      accurate members of the Y class DNA polymerases involved in lesion bypass. Thus,
      herpes primase is one of the least accurate nucleotide polymerizing enzymes
      known.

PMID- 15248766
TI  - Phosphorylation states of translational initiation factors affect mRNA cap
      binding in wheat.
AB  - Phosphorylation of eukaryotic translational initiation factors (eIFs) has been
      shown to be an important means of regulating protein synthesis. Plant initiation
      factors undergo phosphorylation/dephosphorylation under a variety of stress and
      growth conditions. We have shown that recombinant wheat cap-binding protein,
      eIF(iso)4E, produced from E. coli can be phosphorylated in vitro. Phosphorylation
      of eIF(iso)4E has effects on m(7)G cap-binding affinity similar to those of
      phosphorylation of mammalian eIF4E even though eIF(iso)4E lacks an amino acid
      that can be phosphorylated at the residue corresponding to Ser-209, the
      phosphorylation site in mammalian eIF4E. The cap-binding affinity was reduced 1.2
      2.6-fold when eIF(iso)4E was phosphorylated. The in vitro phosphorylation site
      for wheat eIF(iso)4E was identified as Ser-207. Addition of eIF(iso)4G and eIF4B
      that had also been phosphorylated in vitro further reduced cap-binding affinity.
      Temperature-dependent studies showed that DeltaH(degrees) was favorable for cap
      binding regardless of the phosphorylation state of the initiation factors. The
      entropy, however, was unfavorable (negative) except when eIF(iso)4E was
      phosphorylated and interacting with eIF(iso)4G. Phosphorylation may modulate not
      only cap-binding activity, but other functions of eukaryotic initiation factors
      as well.

PMID- 15248767
TI  - Repair of oxidative guanine damage in plasmid DNA by indoles involves proton
      transfer between complementary bases.
AB  - We have used the single electron oxidizing agent (SCN)(2)(*)(-) (generated by
      gamma-irradiation of aqueous thiocyanate) to produce guanyl radicals in plasmid
      DNA. The stable product(s) formed from these radicals can be detected after
      conversion with a base excision repair endonuclease to single strand breaks. The
      yield of enzyme-induced breaks is decreased by the presence during irradiation of
      indole compounds. Rate constants for the reduction of DNA guanyl radicals by
      these indoles can be calculated from the concentration dependence of the
      attenuation in the yield of enzyme sensitive sites. Indoles bearing electron
      donating groups (methoxy or methyl) appear to react at the diffusion-controlled
      rate, but those bearing electron-withdrawing groups (cyano or nitro) are
      significantly less reactive. At physiological pH values, the reduction of a DNA
      guanyl radical involves the transfer of a proton as well as an electron.
      Comparison of the kinetic results with literature thermodynamic data suggests
      that the source of this proton is the complementary base-paired cytosine.

PMID- 15248768
TI  - Combinatorial selection and edited combinatorial selection of phosphorothioate
      aptamers targeting human nuclear factor-kappaB RelA/p50 and RelA/RelA.
AB  - Nuclear factor-kappaB (NF-kappaB) transcription factors are important in
      regulating the immune response and play critical roles in the pathogenesis of
      chronic inflammatory diseases and a variety of human cancers. Agents that target
      specific NF-kappaB dimers may serve as therapeutic agents for the prevention of
      pathogenic immune responses. We have selected monothiophosphate-modified
      aptamers, or "thioaptamers", to the NF-kappaB p50/RelA heterodimer using
      combinatorial selection techniques. We also utilized a "double sieve" or editing
      approach for the generation of thioaptamers with enhanced selectivity to the
      RelA/RelA homodimer. The thioaptamers from these selections and our previous
      selections on the p50/p50 and RelA/RelA homodimers all had unique sequences and
      bound tightly to the recombinant NF-kappaB dimers against which they were
      selected. The selected thioaptamers also appear to maintain their selectivity and
      specificity among other cellular proteins, because they have the ability to bind
      NF-kappaB proteins within nuclear extracts from lipopolysaccharide (LPS)-induced
      macrophages and B cells.

PMID- 15248769
TI  - Studying the folding process of the acylphosphatase from Sulfolobus solfataricus.
      A comparative analysis with other proteins from the same superfamily.
AB  - The folding process of the acylphosphatase from Sulfolobus solfataricus (Sso AcP)
      has been followed, starting from the fully unfolded state, using a variety of
      spectroscopic probes, including intrinsic fluorescence, circular dichroism, and
      ANS binding. The results indicate that an ensemble of partially folded or
      misfolded species form rapidly on the submillisecond time scale after initiation
      of folding. This conformational ensemble produces a pronounced downward curvature
      in the Chevron plot, appears to possess a content of secondary structure similar
      to that of the native state, as revealed by far-UV circular dichroism, and
      appears to have surface-exposed hydrophobic clusters, as indicated by the ability
      of this ensemble to bind to 8-anilino-1-naphthalenesulfonic acid (ANS). Sso AcP
      folds from this conformational state with a rate constant of ca. 5 s(-1) at pH
      5.5 and 37 degrees C. A minor slow exponential phase detected during folding
      (rate constant of 0.2 s(-1) under these conditions) is accelerated by cyclophilin
      A and is absent in a mutant of Sso AcP in which alanine replaces the proline
      residue at position 50. This indicates that for a lower fraction of Sso AcP
      molecules the folding process is rate-limited by the cis-trans isomerism of the
      peptide bond preceding Pro50. A comparative analysis with four other homologous
      proteins from the acylphosphatase superfamily shows that sequence hydrophobicity
      is an important determinant of the conformational stability of partially folded
      states that may accumulate during folding of a protein. A low net charge and a
      high propensity to form alpha-helical structure also emerge as possibly important
      determinants of the stability of partially folded states. A significant
      correlation is also observed between folding rate and hydrophobic content of the
      sequence within this superfamily, lending support to the idea that sequence
      hydrophobicity, in addition to relative contact order and conformational
      stability of the native state, is a key determinant of folding rate.

PMID- 15248770
TI  - Analyzing topography of membrane-inserted diphtheria toxin T domain using BODIPY
      streptavidin: at low pH, helices 8 and 9 form a transmembrane hairpin but helices
      5-7 form stable nonclassical inserted segments on the cis side of the bilayer.
AB  - Low pH-induced membrane insertion by diphtheria toxin T domain is crucial for A
      chain translocation into the cytoplasm. To define the membrane topography of the
      T domain, the exposure of biotinylated Cys residues to the cis and trans bilayer
      surfaces was examined using model membrane vesicles containing a deeply inserted
      T domain. To do this, the reactivity of biotin with external and vesicle
      entrapped BODIPY-labeled streptavidin was measured. The T domain was found to
      insert with roughly 70-80% of the molecules in the physiologically relevant
      orientation. In this orientation, residue 349, located in the loop between
      hydrophobic helices 8 and 9, was exposed to the trans side of the bilayer, while
      other solution-exposed residues along the hydrophobic helices 5-9 region of the T
      domain located near the cis surface. A protocol developed to detect the movement
      of residues back and forth across the membranes demonstrated that T domain
      sequences did not rapidly equilibrate between the cis and the trans sides of the
      bilayer. Binding streptavidin to biotinylated residues prior to membrane
      insertion only inhibited T domain pore formation for residues in the loop between
      helices 8 and 9. Pore formation experiments used an approach avoiding
      interference from transient membrane defects/leakage that may occur upon the
      initial insertion of protein. Combined, these results indicate that at low pH
      hydrophobic helices 8 and 9 form a transmembrane hairpin, while hydrophobic
      helices 5-7 form a nonclassical deeply inserted nontransmembraneous state. We
      propose that this represents a novel pre-translocation state that is distinct
      from a previously defined post-translocation state.

PMID- 15248771
TI  - Cyclization increases the antimicrobial activity and selectivity of arginine- and
      tryptophan-containing hexapeptides.
AB  - Arginine- and tryptophan-rich motifs have been identified in antimicrobial
      peptides with various secondary structures. We synthesized a set of linear
      hexapeptides derived from the sequence AcRRWWRF-NH(2) by substitution of
      tryptophan (W) by tyrosine (Y) or naphthylalanine (Nal) and by replacement of
      arginine (R) by lysine (K) to investigate the role of cationic charge and
      aromatic residues in membrane activity and selectivity. A second set of
      corresponding head-to-tail cyclic analogues was prepared to analyze the role of
      conformational constraints. The biological activity of the linear peptides
      followed the order Nal- >> W- > Y-containing compounds and slightly decreased
      upon R-K substitution. A pronounced activity-improving and bacterial selectivity
      enhancing effect was found upon cyclization of the R- and W-bearing parent
      peptide, whereas the activity-modifying effect of cyclization of Y- and Nal
      containing peptides was low. The analysis of the driving forces of peptide
      interaction with model membranes showed that the activities correlated with the
      partition coefficients and the depths of peptide insertion into neutral and
      negatively charged lipid bilayers. Spectroscopic studies, RP-HPLC, and titration
      calorimetry implied that the combination of cationic and aromatic amino acid
      composition and conformational rigidity afforded a membrane-active, amphipathic
      structure with a highly charged face opposed by a cluster of aromatic side
      chains. However, threshold values of low and high hydrophobicity seemed to exist
      beyond which the activity-enhancing effect of cyclization was negligible. The
      results suggest that cyclization of small peptides of an appropriate amino acid
      composition may serve as a promising strategy in the design of antimicrobial
      peptides.

PMID- 15248772
TI  - Binding of cationic porphyrin to isolated and encapsidated viral DNA analyzed by
      comprehensive spectroscopic methods.
AB  - The complexation of tetrakis(4-N-methylpyridyl)porphyrin (TMPyP) with free and
      encapsidated DNA of T7 bacteriophage was investigated. To identify binding modes
      and relative concentrations of bound TMPyP forms, the porphyrin absorption
      spectra at various base pair/porphyrin ratios were analyzed. Spectral
      decomposition, fluorescent lifetime, and circular dichroism measurements proved
      the presence of two main binding types of TMPyP, e.g., external binding and
      intercalation both in free and in encapsidated DNA. Optical melting studies
      revealed that TMPyP increases the strand separation temperature of both free and
      native phage DNA and does not change the phase transition temperature of phage
      capsid proteins. From these findings we concluded that TMPyP binding does not
      influence the protein structure and/or the protein-DNA interaction. A combined
      analysis of absorption spectra and fluorescence decay curves made possible the
      determination of concentrations of free, externally bound, and intercalated
      porphyrin. As a perspective, our results facilitate a qualitative analysis of the
      TMPyP binding process at various experimental conditions.

PMID- 15248773
TI  - Nikkomycin biosynthesis: formation of a 4-electron oxidation product during
      turnover of NikD with its physiological substrate.
AB  - Nikkomycins are peptidyl nucleoside antibiotics that act as therapeutic
      antifungal agents in humans and easily degraded insecticides in agriculture. The
      nikkomycin peptidyl moiety contains a pyridyl residue derived from L-lysine. The
      first step in peptidyl biosynthesis is an aminotransferase-catalyzed reaction
      that converts L-lysine to Delta(1)- or Delta(2)-piperideine-2-carboxylate (P2C).
      Spectral, chromatographic, and kinetic analyses show that the aerobic reaction of
      nikD with P2C results in the stoichiometric formation of picolinate, accompanied
      by the reduction of 2 mol of oxygen to hydrogen peroxide. A high resolution HPLC
      method, capable of separating picolinate, nicotinate and isonicotinate, was
      developed and used in product identification. NikD contains 1 mol of covalently
      bound FAD and exists as a monomer in solution. Reductive and oxidative titrations
      with dithionite and potassium ferricyanide, respectively, show that FAD is the
      only redox-active group in nikD. Anaerobic reaction of nikD with 1 mol of P2C
      results in immediate reduction of enzyme-bound FAD. Because nikD is an obligate 2
      electron acceptor, it is proposed that the observed 4-electron oxidation of P2C
      to picolinate occurs via a mechanism involving two successive nikD-catalyzed 2
      electron oxidation steps. In addition to nikkomycins, a nikD-like reaction is
      implicated in the biosynthesis of an L-lysine-derived pyridyl moiety found in
      streptogramin group B antibiotics that are used as part of a last resort
      treatment for severe infections due to gram positive bacteria.

PMID- 15248774
TI  - Solution structure and structural dynamics of envelope protein domain III of
      mosquito- and tick-borne flaviviruses.
AB  - The mosquito-borne West Nile (WNV) and dengue 2 (DEN2V) viruses and tick-borne
      Langat (LGTV) and Omsk hemorrhagic fever (OHFV) viruses are arthropod-borne
      flaviviruses (family Flaviviridae, genus Flavivirus). These viruses are quite
      similar at both the nucleotide and amino acid level, yet they are very divergent
      in their biological properties and in the diseases they cause. The objective of
      this study was to examine the putative receptor-binding domains of the
      flaviviruses, the envelope (E) protein domain III (D3), which assume very similar
      structures either as part of the whole envelope protein or as individual
      entities, and to define the biophysical properties that distinguish among these
      viruses. Circular dichroism and Fourier transform infrared spectroscopy were
      employed to monitor the solution structure of these proteins. While the
      spectroscopic results found that the D3 from each of these viruses is composed of
      either beta-sheets or beta-turns, which is consistent with X-ray crystal data for
      tick-borne encephalitis and dengue viruses, these results reveal that recombinant
      D3s (rED3s) derived from tick-borne flaviviruses (LGT-rED3 and OHF-rED3) were
      similar to each other, while those from mosquito-borne flaviviruses (WN-rED3 and
      DEN-rED3) were similar to each other yet distinct from rED3 of the tick-borne
      viruses. Protein dynamic studies probed by fluorescence quenching and
      hydrogen/deuterium exchange found that the rED3s are dynamic entities. The tick
      borne proteins again exhibit very similar dynamic properties, which are different
      from the mosquito-borne proteins. The WN-rED3 is significantly less stable than
      the other three rED3s. Overall, these differences in biophysical properties
      correlate with biological properties of these viruses that tick-borne
      flaviviruses are more stable than mosquito-borne flaviviruses.

PMID- 15248775
TI  - A trojan horse approach for silencing thymidylate synthase.
AB  - In this paper we present a new and possibly more effective way of inhibiting
      thymidylate synthase (TS) in cells than through the use of substrate analogue
      inhibitors. An inactive double mutant of TS (DM), Arg(126)Glu/Cys(146)Trp, is
      shown to progressively impair the reactivation of native Escherichia coli TS when
      the two are denatured together in vitro. The individual single mutant proteins
      Arg(126)Glu and Cys(146)Trp showed little or no inhibition. When the DM is
      introduced into E. coli and induced from an expression plasmid, the mutant
      subunits act as a decoy in deceiving newly formed native TS subunits to fold with
      them to yield inactive heterodimers. As a consequence of the depletion of TS, the
      cells die a "thymineless" death when grown in medium devoid of thymine. Addition
      of thymine to the medium enables the cells to grow normally, although only very
      low levels of TS activity could be detected in those cells containing induced DM.
      The individual single-site mutations of the DM, Arg(126)Glu and Cys(146)Trp, did
      not inhibit growth, as might be expected from the in vitro studies. However, when
      a nontoxic level of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) is added to
      growing DM-transformed cells, the combination is lethal to the cells. These
      experiments suggest that a similar dominant-negative response to the DM of TS
      could be affected in tumor cells, for which preliminary evidence is presented.
      This technique, either alone or combined with other modalities, suggest a new
      approach to targeting cells for chemotherapy.

PMID- 15248776
TI  - Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1
      (hSCAN-1): identification of residues essential for enzyme activity and the
      Ca(2+)-induced conformational change.
AB  - Human soluble calcium-activated nucleotidase 1 (hSCAN-1) is the human homologue
      of soluble apyrases found in blood-sucking insects. This family of nucleotidases
      is unrelated in sequence to more well-studied nucleotidases, and very little is
      known about the enzymatic mechanism. By multiple sequence alignment, eight
      regions that are highly conserved in the hSCAN-1 family were identified and
      named. To identify amino acids important for catalytic activity and enzyme
      specificity, seven point mutations were constructed, expressed in bacteria,
      refolded, purified, and characterized. Substitution of glutamic acid 130 with
      tyrosine resulted in dramatically increased nucleotidase activities, while
      mutagenesis of aspartic acid 151 to alanine and aspartic acid 84 to alanine
      completely abolished activity. Mutagenesis of arginine 133 and arginine 271
      resulted in enzymes with very little nucleotidase activity. Mutagenesis of
      aspartic acid 175 to alanine and glycine 122 to glutamic acid had smaller
      negative effects on enzyme activities. Previously, our laboratory showed that
      calcium triggers a conformational change in hSCAN-1 necessary for nucleotidase
      activity. Here we show that several mutants (D84A, R133A, and D151A) that lost
      most of their activity were unable to undergo the conformational change induced
      by Ca(2+), as shown by Cibacron blue binding, limited proteolysis, and tryptophan
      fluorescence. We conclude that aspartic acid residues 84 and 151, as well as
      arginine residue 133, are essential for the Ca(2+)-induced conformational change
      that is necessary for enzyme activity. Aspartic acid 175 and glutamic acid 130
      are important for determining substrate specificity. In addition, we show that
      Sr(2+), unlike Mg(2+) and other divalent cations, can substitute for Ca(2+) to
      induce the conformational change necessary for enzyme activity. However, Sr(2+)
      cannot substitute for Ca(2+) to support nucleotide hydrolysis, presumably because
      Sr(2+) cannot substitute for Ca(2+) in its second role as a nucleotide
      cosubstrate. The ramifications of our results on the interpretation of a recently
      published crystal structure are discussed. This information will facilitate
      future engineering of this enzyme designed to enhance its ability to hydrolyze
      ADP and thus increase its potential for therapeutic use in the treatment of
      pathological ischemic events triggered via activation of platelets by ADP.

PMID- 15248777
TI  - Specificity of the synergistic anion for iron binding by ferric binding protein
      from Neisseria gonorrhoeae.
AB  - Ferric binding protein in Neisseria gonorrhoeae (nFbpA) transports iron from
      outer membrane receptors for host proteins across the periplasm to a permease in
      an alternative pathway to the use of siderophores in some pathogenic bacteria.
      Phosphate and nitrilotriacetate, both at pH 8, and vanadate at pH 9 are shown to
      be synergistic in promoting ferric binding to nFbpA, in contrast to carbonate and
      sulfate. Interestingly, only phosphate produces the fully closed conformation of
      nFbpA as defined by native electrophoresis. The role of phosphate was probed by
      constructing three mutants: Q58E, Q58R, and G140H. The anion and iron binding
      properties of the Q58E mutant are similar to the wild-type protein, implying that
      one phosphate oxygen is a hydrogen bond donor and may in part define the
      specificity of nFbpA for phosphate over sulfate. Phosphate is a weakly
      synergistic anion in the Q58R and G140H mutants, and these mutants do not form
      completely closed structures. Ferric binding was investigated by both isothermal
      titration and differential scanning calorimetry. The apparent affinity of nFbpA
      for iron in a solution of 30 mM citrate is 1 order of magnitude larger in the
      presence (K(app)= 1.7 x 10(5) M(-1)) of phosphate than in its absence (K(app) =
      1.6 x 10(4) M(-1)) at pH 7. Similar results were obtained at pH 8. This increase
      in affinity with phosphate as well as the formation of closed structure allows
      nFbpA to compete for free ferric ions in solution and suggests that ferric
      binding to nFbpA is regulated by the synergistic phosphate anion at sites of iron
      uptake.

PMID- 15248778
TI  - Supramolecular photosystem II organization in grana thylakoid membranes: evidence
      for a structured arrangement.
AB  - The distribution of photosystem (PS) II complexes in stacked grana thylakoids
      derived from electron microscopic images of freeze-fractured chloroplasts are
      examined for the first time using mathematical methods. These characterize the
      particle distribution in terms of a nearest neighbor distribution function and a
      pair correlation function. The data were compared with purely random
      distributions calculated by a Monte Carlo simulation. The analysis reveals that
      the PSII distribution in grana thylakoids does not correspond to a random protein
      mixture but that ordering forces lead to a structured arrangement on a
      supramolecular level. Neighboring photosystems are significantly more separated
      than would be the case in a purely random distribution. These results are
      explained by structural models, in which boundary lipids and light-harvesting
      complex (LHC) II trimers are arranged between neighboring PSII. Furthermore, the
      diffusion of PSII was analyzed by a Monte Carlo simulation with a protein density
      of 80% area occupation (determined for grana membranes). The mobility of the
      photosystems is severely reduced by the high protein density. From an estimate of
      the mean migration time of PSII from grana thylakoids to stroma lamellae, it
      becomes evident that this diffusion contributes significantly to the velocity of
      the repair cycle of photoinhibited PSII.

PMID- 15248779
TI  - Proteomic analysis of the photosystem I light-harvesting antenna in tomato
      (Lycopersicon esculentum).
AB  - Until now, more genes of the light-harvesting antenna of higher-plant photosystem
      I (PSI) than proteins have been described. To improve our understanding of the
      composition of light-harvesting complex I (LHCI) of tomato (Lycopersicon
      esculentum), we combined one- and two-dimensional (1-D and 2-D, respectively) gel
      electrophoresis with immunoblotting and tandem mass spectrometry (MS/MS).
      Separation of PSI with high-resolution 1-D gels allowed separation of five bands
      attributed to proteins of LHCI. Immunoblotting with monospecific antibodies and
      MS/MS analysis enabled the correct assignment of the four prominent bands to
      light-harvesting proteins Lhca1-4. The fifth band was recognized by only the
      Lhca1 antibody. Immunodetection as well as mass spectrometric analysis revealed
      that these protein bands contain not only the eponymous protein but also other
      Lhca proteins, indicating a heterogeneous protein composition of Lhca bands.
      Additionally, highly sensitive MS/MS allowed detection of a second Lhca4 isoform
      and of Lhca5. These proteins had not been described before on the protein level
      in higher plants. Two-dimensional gel electrophoresis revealed an even more
      diverse composition of individual Lhca proteins than was apparent from 1-D gels.
      For each of the four prominent Lhca proteins, four to five isoforms with
      different isoelectric points could be identified. In the case of Lhca1, Lhca4,
      and Lhca3, additional isoforms with slightly differing molecular masses were
      identified. Thus, we were able to detect four to ten isoforms of each individual
      Lhca protein in PSI. Reasons for the origin of Lhca heterogeneity are discussed.
      The observed variety of Lhca proteins and their isoforms is of particular
      interest in the context of the recently published crystal structure of
      photosystem I from pea, which showed the presence of only four Lhca proteins per
      photosystem I. These findings indicate that several populations of photosystem I
      that differ in their Lhca composition may exist.

PMID- 15248780
TI  - Sequences of B-chain/domain 1-10/1-9 of insulin and insulin-like growth factor 1
      determine their different folding behavior.
AB  - Although insulin and insulin-like growth factor-1 (IGF-1) belong to one family,
      insulin folds into one thermodynamically stable structure, while IGF-1-folds into
      two thermodynamically stable structures (native and swap forms). We have
      demonstrated previously that the bifurcating folding behavior of IGF-1 is mainly
      controlled by its B-domain. To further elucidate which parts of the sequences
      determine their different folding behavior, by exchanging the N-terminal
      sequences of mini-IGF-1 and recombinant porcine insulin precursor (PIP), we
      prepared four peptide models: [1-9]PIP, [1-10]mini-IGF-1, [1-4]PIP, and [1-5]mini
      IGF-1 by means of protein engineering, and their disulfide rearrangement, V8
      digestion, circular dichroic spectra, disulfide stability, and in vitro refolding
      were investigated. Among them only [1-9]PIP, like mini-IGF-1/IGF-1, was expressed
      in yeast as two isomers: isomer 1 (corresponding to swap IGF-1) and isomer 2
      (corresponding to native IGF-1), which are supported by the experimental results
      of disulfide rearrangements, peptide mapping of V8 endoprotenase digests,
      circular dichroic analysis, in vitro refolding, and disulfide stability analysis.
      The other peptide models, [1-10]mini-IGF-1, [1-4]PIP, and [1-5]mini-IGF-1, fold
      into one stable structure as PIP does, which indicates that sequence 1-4 of mini
      IGF-1 is important for the folding behavior of mini-IGF-1/IGF-1 but not
      sufficient to lead to a bifurcating folding. The results demonstrated that the
      folding information, by which mini-IGF-1/IGF-1-folds into two thermodynamically
      structures, is encoded/written in its sequence 1-9, while sequences 1-10 of B
      chain in insulin/PIP play an important role in the guide of its unique disulfide
      pairing during the folding process.

PMID- 15248781
TI  - Characterization of the purified hyaluronan synthase from Streptococcus
      equisimilis.
AB  - Hyaluronan synthase (HAS) utilizes UDP-GlcUA and UDP-GlcNAc in the presence of
      Mg(2+) to form the GAG hyaluronan (HA). The purified HAS from Streptococcus
      equisimilis (seHAS) shows high fidelity in that it only polymerizes the native
      substrates, UDP-GlcNAc and UDP-GlcUA. However, other uridinyl nucleotides and UDP
      sugars inhibited enzyme activity, including UDP-GalNAc, UDP-Glc, UDP-Gal, UDP
      GalUA, UMP, UDP, and UTP. Purified seHAS was approximately 40% more active in 25
      mM, compared to 50 mM, PO(4) in the presence of either 50 mM NaCl or KCl, and
      displayed a slight preference for KCl over NaCl. The pH profile was surprisingly
      broad, with an effective range of pH 6.5-11.5 and the optimum between pH 9 and
      10. SeHAS displayed two apparent pK(a) values at pH 6.6 and 11.8. As the pH was
      increased from approximately 6.5, both K(m) and V(max) increased until pH
      approximately 10.5, above which the kinetic constants gradually declined.
      Nonetheless, the overall catalytic constant (120/s) was essentially unchanged
      from pH 6.5 to 10.5. The enzyme is temperature labile, but more stable in the
      presence of substrate and cardiolipin. Purified seHAS requires exogenous
      cardiolipin for activity and is very sensitive to the fatty acyl composition of
      the phospholipid. The enzyme was inactive or highly activated by synthetic
      cardiolipins containing, respectively, C14:0 or C18:1(Delta9) fatty acids. The
      apparent E(act) for HA synthesis is 40 kJ (9.5 kcal/mol) disaccharide. Increasing
      the viscosity by increasing concentrations of PEG, ethylene glycol, glycerol, or
      sucrose inhibited seHAS activity. For PEGs, the extent of inhibition was
      proportional to their molecular mass. PEGs with average masses of 2.7, 11.7, and
      20 kg/mol caused 50% inhibition of V(max) at 21, 6.5, and 3.5 mM, respectively.
      The apparent K(i) values for ethylene glycol, glycerol, and sucrose were,
      respectively, 4.5, 3.3, and 1.2 mM.

PMID- 15248782
TI  - Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5)
      and comparison to the Escherichia coli TrmD protein.
AB  - A human TRM5 cDNA has been cloned and recombinant tRNA-N(1)G37 methyltransferase
      was produced. The recombinant enzyme methylates the N1 position of guanosine 37
      (G37) in selected tRNA transcripts utilizing S-adenosyl methionine. The effects
      of RNA sequence and structure on the methylation reaction in comparison between
      the Escherichia coli TrmD and human TRM5 recombinant enzymes are presented. G37
      methylation by TRM5 occurs regardless of the nature of the nucleotide at position
      36. TRM5 also methylates inosine at position 37 unlike TrmD, which recognizes the
      G36pG37 motif preferentially and does not methylate inosine. New evidence is
      presented concerning TrmD showing that with some tRNA species, A at position 36
      is also recognized. The TRM5 enzyme is sensitive to subtle changes in the tRNA
      protein tertiary interaction leading to loss of activity. The TrmD enzyme is more
      tolerant of alterations in tRNA-protein tertiary interactions as long as the core
      tRNA structure and the G36pG37 are present. The TRM5 enzyme does not have an
      absolute requirement for magnesium ions, whereas TrmD requires magnesium to
      express activity. TRM5 demonstrates much higher affinity for substrates with K(m)
      values for tRNA that are nanomolar. TrmD has K(m) values for tRNA in the
      micromolar range. Recombinant TRM5 appears to function as a 60 772 Da monomer,
      while recombinant TrmD functions as a homodimer of 30 586 Da subunits.
      Bioinformatic analysis of the human TRM5 genomic locus (KIAA1393) have identified
      TRM5 homologues in eukaryotes and archaea; however, no significantly homologous
      regions were identified in any prokaryotes including the TrmD gene.

PMID- 15248783
TI  - Origins of delays in monolayer kinetics: phospholipase A2 paradigm.
AB  - The interfacial kinetic paradigm is adopted to model the kinetic behavior of pig
      pancreatic phospholipase A(2) (PLA2) at the monolayer interface. A short delay of
      about a minute to the onset of the steady state is observed under all monolayer
      reaction progress conditions, including the PLA2-catalyzed hydrolysis of
      didecanoylphosphatidyl-choline (PC10) and -glycerol (PG10) monolayers as analyzed
      in this paper. This delay is independent of enzyme concentration and surface
      pressure and is attributed to the equilibration time by stationary diffusion of
      the enzyme added to the stirred subphase to the monolayer through the intervening
      unstirred aqueous layer. The longer delays of up to several hours, seen with the
      PC10 monolayers at >15 mN/m, are influenced by surface pressure as well as enzyme
      concentration. Virtually all features of the monolayer reaction progress are
      consistent with the assumption that the product accumulates in the substrate
      monolayer, although the products alone do not spread as a compressible monolayer.
      These results rule out models that invoke slow "activation" of PLA2 on the
      monolayer. The observed steady-state rate on monolayers after the delays is <1%
      of the rate observed with micellar or vesicles substrates of comparable
      substrate. Together these results suggest that the monolayer steady-state rate
      includes contributions from steps other than those of the interfacial turnover
      cycle. Additional considerations that provide understanding of the pre-steady
      state behaviors and other nonideal effects at the surface are also discussed.

PMID- 15248784
TI  - In vitro selection of state-specific peptide modulators of G protein signaling
      using mRNA display.
AB  - The G protein regulatory (GPR) motif is a approximately 20-residue conserved
      domain that acts as a guanine dissociation inhibitor (GDI) for G(i/o)(alpha)
      subunits. Here, we describe the isolation of peptides derived from a GPR
      consensus sequence using mRNA display selection libraries. Biotinylated
      G(i)(alpha)(1), modified at either the N or C terminus, serves as a high-affinity
      binding target for mRNA-displayed GPR peptides. In vitro selection using mRNA
      display libraries based on the C terminus of the GPR motif revealed novel peptide
      sequences with conserved residues. Surprisingly, selected peptides contain
      mutations to a highly conserved Arg in the GPR motif, previously shown to be
      crucial for binding and inhibition activities. The dominant peptide from the
      selection, R6A, and a minimal 9-mer peptide, R6A-1, do not contain Arg residues
      yet retain high affinity (K(D) = 60 and 200 nM, respectively) and specificity for
      the GDP-bound state of G(i)(alpha)(1), as measured by surface plasmon resonance.
      The selected peptides also maintain GDI activity for G(i)(alpha)(1), inhibiting
      both the exchange of GDP in GTPgammaS binding assays and the AlF(4)(-)-stimulated
      enhancement of intrinsic tryptophan fluorescence. The kinetics of GDI activity,
      however, are different for the selected peptides and demonstrate biphasic
      kinetics, suggesting a complex mechanism for inhibition. Like the GPR motif, the
      R6A and R6A-1 peptides compete with G(betagamma) subunits for binding to
      G(i)(alpha)(1), suggesting their use as activators of G(betagamma) signaling.

PMID- 15248785
TI  - Application of the local-bulk partitioning and competitive binding models to
      interpret preferential interactions of glycine betaine and urea with protein
      surface.
AB  - Two thermodynamic models have been developed to interpret the preferential
      accumulation or exclusion of solutes in the vicinity of biopolymer surface and
      the effects of these solutes on protein processes. The local-bulk partitioning
      model treats solute (and water) as partitioning between the region at/or near the
      protein surface (the local domain) and the bulk solution. The solvent exchange
      model analyzes a 1:1 competition between water and solute molecules for
      independent surface sites. Here we apply each of these models to interpret
      thermodynamic data for the interactions of urea and the osmoprotectant glycine
      betaine (N,N,N-trimethylglycine; GB) with the surface exposed in unfolding the
      marginally stable lacI HTH DNA binding domain. The partition coefficient K(P)
      quantifying accumulation of urea at this protein surface (K(P) approximately
      equal 1.1) is only weakly dependent on urea concentration up to 6 M urea.
      However, K(P) quantifying exclusion of GB from the vicinity of this protein
      surface increases from 0.83 (extrapolated to 0 M GB) to 1.0 (indicating that
      local and bulk GB concentrations are equal) at 4 M GB (activity > 40 M). We
      interpret the significant concentration dependence of K(P) for GB, predicted to
      be general for excluded, nonideal solutes such as GB, as a modest (8%)
      attenuation of the GB concentration dependence of solute nonideality in the local
      domain relative to that in the bulk solution. Above 4 M, K(P) for the interaction
      of GB with the surface exposed in protein unfolding is predicted to exceed unity,
      which explains the maximum in thermal stability observed for RNase and lysozyme
      at 4 M GB (Santoro, M. M., Liu, Y. F., Khan, S. M. A., Hou, L. X., and Bolen, D.
      W. (1992) Biochemistry 31, 5278-5283). Both thermodynamic models provide good two
      parameter fits to GB and urea data for lacI HTH unfolding over a wide
      concentration range. The solute partitioning model allows for a full spectrum of
      attenuation effects in the local domain, encompasses the cases treated by the
      competitive binding model, and provides a somewhat better two-parameter fit of
      effects of high GB concentration on lacI HTH stability. Parameters of this fit
      should be applicable to isothermal and thermal unfolding data for all proteins
      with similar compositions of surface exposed in unfolding.

PMID- 15248786
TI  - The benefits of exercise training for quality of life in HIV/AIDS in the post
      HAART era.
AB  - The use of highly active antiretroviral therapy (HAART) has served to
      significantly reduce the mortality of HIV-infected persons. However, this
      treatment is associated with a host of adverse effects: fatigue, nausea, pain,
      anxiety and depression. Rather than utilise traditional pharmacological
      treatments for these effects, many HIV/AIDS patients are utilising adjunct
      therapies to maintain their quality of life while they undergo treatment.
      Exercise has consistently been listed as one of the most popular self-care
      therapies and a small number of studies have been conducted to examine the impact
      of exercise on the most common self-reported symptoms of HIV and AIDS and the
      adverse effects of treatment. Although the results are generally positive, there
      are clear limitations to this work. The existing studies have utilised small
      samples and experienced high rates of attrition. In addition, the majority of the
      studies were conducted prior to the widespread use of HAART, which limits the
      ability to generalise these data. As a result, data from other chronic disease
      and healthy samples are used to suggest that exercise has the potential to be a
      beneficial treatment across the range of symptoms and adverse effects experienced
      by HIV-infected individuals. However, additional research is required with this
      population to demonstrate these effects.

PMID- 15248787
TI  - Heat stroke : a review of cooling methods.
AB  - The prognosis of heat stroke in patients is directly related to the degree of
      hyperthermia and its duration. Therefore, the most important feature in the
      treatment of heat stroke is rapid cooling. Several cooling methods have been
      presented in the literature including immersion in water at different
      temperatures, evaporative cooling, ice pack application, pharmacological
      treatment and invasive techniques. This article describes the various cooling
      techniques in terms of efficacy, availability, adverse effects and mortality
      rate. Data suggest that cooling should be initiated immediately at time of
      collapse and should be based on feasible field measures including ice or tepid
      water (1-16 degrees C), which are readily available. In the emergency department,
      management should be matched to the patient's age and medical background and
      include immersion in ice water (1-5 degrees C) or evaporative cooling.

PMID- 15248789
TI  - The effects of the substitution on the imidazole ligand on the photochemical
      properties of fac-[Mn(CO)3(phen)(Imidazole)](SO3CF3) complexes.
AB  - Photochemical and photophysical data are reported for a series of fac
      [Mn(CO)(3)(phen)(Im-R)](SO(3)CF(3)) complexes, where phen is 1,10-phenanthroline
      and Im is imidazole. Intraligand and metal-to-ligand charge transfer (MLCT)
      transitions are observed in the electronic absorption spectra of these complexes
      and are sensitive to the nature of the ligand substituent. At room temperature
      the emission spectra show a clear progression from broad structureless MLCT to
      highly structured pi-pi* emission on going from R = -H, -CH(3), -C(6)H(5), to 
      Metro, where Metro is 2-methyl-5-nitroimidazole. Even at low temperatures the
      latter complexes show only the pi-pi* emission. The trend in the photophysical
      properties found in the emission spectra parallels the changes in the
      photochemical properties with the electron-donating or electron-withdrawing power
      of the substituent on the imidazole ligand. Although MLCT irradiation of the
      complexes with R = -H, -CH(3) leads to the mer-[Mn(CO)(3)(phen)(Im-R)](+)
      isomers, the complexes with the imidazole ligand substituted by -C(6)H(5) or 
      Metro release the Im-R ligand and produce the stereoretentive fac
      [Mn(CO)(3)(phen)(S)](+) complexes. The stereochemical fate and mechanistic
      implications of the photolysis reactions are discussed in terms of the nature of
      ligand substitution.

PMID- 15248791
TI  - Embedded-explicit emergent literacy intervention I: Background and description of
      approach.
AB  - This article, the first of a two-part series, provides background information and
      a general description of an emergent literacy intervention model for at-risk
      preschoolers and kindergartners. The embedded-explicit intervention model
      emphasizes the dual importance of providing young children with socially embedded
      opportunities for meaningful, naturalistic literacy experiences throughout the
      day, in addition to regular structured therapeutic interactions that explicitly
      target critical emergent literacy goals. The role of the speech-language
      pathologist (SLP) in the embedded-explicit model encompasses both indirect and
      direct service delivery: The SLP consults and collaborates with teachers and
      parents to ensure the highest quality and quantity of socially embedded literacy
      focused experiences and serves as a direct provider of explicit interventions
      using structured curricula and/or lesson plans. The goal of this integrated model
      is to provide comprehensive emergent literacy interventions across a spectrum of
      early literacy skills to ensure the successful transition of at-risk children
      from prereaders to readers.

PMID- 15248792
TI  - Embedded-explicit emergent literacy intervention II: goal selection and
      implementation in the early childhood classroom.
AB  - This article, the second in a two-part series, provides guidance to speech
      language pathologists (SLPs) for implementing the explicit component of the
      embedded-explicit emergent literacy intervention model for at-risk preschool and
      kindergarten children. The explicit component refers to the provision of regular
      structured therapeutic interactions that intentionally target critical emergent
      literacy goals. This article describes fundamental principles of explicit
      literacy instruction, identifies literacy domains targeted as part of explicit
      literacy instruction, and presents examples of how early childhood classrooms can
      be organized to implement the embedded-explicit model.

PMID- 15248793
TI  - Computer-supported phonological awareness intervention for kindergarten children
      with specific language impairment.
AB  - PURPOSE: The purpose of the present study was to determine whether kindergarten
      children with specific language impairment (SLI) could develop phonological
      awareness skills through computer intervention and whether speech manipulation
      (i.e., slowing speech rate and enhancing transitions) in instruction produced
      additional learning. METHOD: The effects of a computer-supported phonological
      awareness program on a variety of items, including word analysis, syllable
      analysis, rhyme, phoneme analysis, syllable synthesis, and phoneme synthesis,
      were tested following a pretest-posttest 1-posttest 2 design. Twenty-four
      kindergarten children with SLI in the Netherlands received 3.5 hr of phonological
      awareness intervention via a computer program using either normal speech (12
      children) or manipulated speech (12 children). A control group of 12 kindergarten
      children with SLI played computer vocabulary games. RESULTS: The results showed
      positive effects of the intervention for the normal speech group. Eighteen weeks
      later, the effect size was still substantial; however, no additional effects of
      speech manipulation were found. CLINICAL IMPLICATIONS: The results suggest that
      kindergarten children with SLI benefit from computer intervention for
      phonological awareness skills.

PMID- 15248794
TI  - African American and Caucasian preschoolers' use of decontextualized language:
      literate language features in oral narratives.
AB  - PURPOSE: Low-income preschoolers' use of literate language features in oral
      narratives across three age groups (3-, 4-, and 5-year-olds) and two ethnic
      groups (Caucasian and African American) was examined. METHOD: Sixty-seven
      preschoolers generated a story using a wordless picture book. The literate
      language features examined were simple and complex elaborated noun phrases,
      adverbs, conjunctions, and mental/linguistic verbs. RESULTS: Literate language
      features occurred at measurable rates for 3- to 5-year-old children. Conjunction
      use was positively associated with the use of complex elaborated noun phrases and
      adverbs, and the use of complex and simple elaborated noun phrases was inversely
      related. There were no differences between African American and Caucasian
      children's usage rates. Age-related differences were observed in the use of
      mental/linguistic verbs and conjunctions. CLINICAL IMPLICATIONS: The importance
      of supporting decontextualized language skills during the preschool period is
      discussed.

PMID- 15248788
TI  - Effects of androgenic-anabolic steroids in athletes.
AB  - Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone
      testosterone. They can exert strong effects on the human body that may be
      beneficial for athletic performance. A review of the literature revealed that
      most laboratory studies did not investigate the actual doses of AAS currently
      abused in the field. Therefore, those studies may not reflect the actual
      (adverse) effects of steroids. The available scientific literature describes that
      short-term administration of these drugs by athletes can increase strength and
      bodyweight. Strength gains of about 5-20% of the initial strength and increments
      of 2-5 kg bodyweight, that may be attributed to an increase of the lean body
      mass, have been observed. A reduction of fat mass does not seem to occur.
      Although AAS administration may affect erythropoiesis and blood haemoglobin
      concentrations, no effect on endurance performance was observed. Little data
      about the effects of AAS on metabolic responses during exercise training and
      recovery are available and, therefore, do not allow firm conclusions. The main
      untoward effects of short- and long-term AAS abuse that male athletes most often
      self-report are an increase in sexual drive, the occurrence of acne vulgaris,
      increased body hair and increment of aggressive behaviour. AAS administration
      will disturb the regular endogenous production of testosterone and gonadotrophins
      that may persist for months after drug withdrawal. Cardiovascular risk factors
      may undergo deleterious alterations, including elevation of blood pressure and
      depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol
      levels. In echocardiographic studies in male athletes, AAS did not seem to affect
      cardiac structure and function, although in animal studies these drugs have been
      observed to exert hazardous effects on heart structure and function. In studies
      of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to
      be strongly affected by AAS. Generally, AAS seem to induce increments of
      aggression and hostility. Mood disturbances (e.g. depression, [hypo-]mania,
      psychotic features) are likely to be dose and drug dependent. AAS dependence or
      withdrawal effects (such as depression) seem to occur only in a small number of
      AAS users. Dissatisfaction with the body and low self-esteem may lead to the so
      called 'reverse anorexia syndrome' that predisposes to the start of AAS use. Many
      other adverse effects have been associated with AAS misuse, including disturbance
      of endocrine and immune function, alterations of sebaceous system and skin,
      changes of haemostatic system and urogenital tract. One has to keep in mind that
      the scientific data may underestimate the actual untoward effects because of the
      relatively low doses administered in those studies, since they do not approximate
      doses used by illicit steroid users. The mechanism of action of AAS may differ
      between compounds because of variations in the steroid molecule and affinity to
      androgen receptors. Several pathways of action have been recognised. The enzyme 5
      alpha-reductase seems to play an important role by converting AAS into
      dihydrotestosterone (androstanolone) that acts in the cell nucleus of target
      organs, such as male accessory glands, skin and prostate. Other mechanisms
      comprises mediation by the enzyme aromatase that converts AAS in female sex
      hormones (estradiol and estrone), antagonistic action to estrogens and a
      competitive antagonism to the glucocorticoid receptors. Furthermore, AAS
      stimulate erythropoietin synthesis and red cell production as well as bone
      formation but counteract bone breakdown. The effects on the cardiovascular system
      are proposed to be mediated by the occurrence of AAS-induced atherosclerosis (due
      to unfavourable influence on serum lipids and lipoproteins), thrombosis,
      vasospasm or direct injury to vessel walls, or may be ascribed to a combination
      of the different mechanisms. AAS-induced increment of muscle tissue can be
      attributed to hypertrophy and the formation of new muscle fibres, in which key
      roles are played by satellite cell number and ultrastructure, androgen receptors
      and myonuclei.

PMID- 15248795
TI  - The effects of verbal support strategies on small-group peer interactions.
AB  - PURPOSE: This study investigated whether child care providers could learn to
      facilitate peer interactions by using verbal support strategies (e.g., prompts,
      invitations, or suggestions to interact) during naturalistic play activities.
      METHOD: Seventeen caregivers were randomly assigned to experimental and control
      groups, stratified by center so that staff from one center could attend the
      training program together. The experimental group received inservice training on
      how to facilitate peer interaction; the control group received training on adult
      child communication strategies. Caregivers in the experimental group were taught
      to facilitate children's interactions with their peers by using indirect
      referrals (e.g., alerting children to situational information, offering praise)
      and direct referrals (e.g., telling a child what to say to a peer, inviting
      children to play together). RESULTS: At posttest, the caregivers in the
      experimental group used more verbal supports for peer interaction than the
      caregivers in the control group. Specifically, they used more utterances to
      promote communication between peers and to invite children to interact together.
      In turn, the children in the experimental group initiated interactions with peers
      more often and engaged in extended peer sequences more often than the children in
      the control group. CLINICAL IMPLICATIONS: The results support the viability of
      this training model in early childhood education settings and suggest that future
      research of its effects with children who have disabilities is warranted.

PMID- 15248796
TI  - Variable production of African American English across oracy and literacy
      contexts.
AB  - Many African American students produce African American English (AAE) features
      that are contrastive to Standard American English (SAE). The AAE-speaking child
      who is able to dialect shift, that is, to speak SAE across literacy contexts,
      likely will perform better academically than the student who is not able to
      dialect shift. METHOD: This investigation examined the AAE productions of 50
      typically developing African American third graders across three language
      contexts-picture description, oral reading of SAE text, and writing. RESULTS: All
      participants produced AAE during picture description. A downward shift in
      contrastive AAE features was evident between spoken discourse and the literacy
      contexts. More students produced more AAE features during picture description
      than writing. Both morphosyntactic and phonological features characterized the
      picture description context. Phonological features predominated during oral
      reading. In contrast, morphosyntactic features were the most dominant feature in
      writing. CLINICAL IMPLICATIONS: The findings are discussed in terms of dialect
      shifting abilities of African American students and the role of writing as a
      special context to support their entry into dialect shifting.

PMID- 15248797
TI  - Description of a program for social language intervention: "if you can have a
      conversation, you can have a relationship".
AB  - Adolescents with impaired language comprehension and formulation skills often
      experience difficulty keeping up with the linguistic and social demands of peer
      interaction. This clinical exchange describes an individualized treatment program
      designed to increase the conversational skill of an adolescent male with language
      impairment. Treatment focused on increasing awareness of the listener's needs and
      on balancing the exchange of conversational turns. Clinical performance, parent
      report, and client report were used to assess outcomes.

PMID- 15248798
TI  - The AuD Program at Gallaudet University.
AB  - Gallaudet University was among the first universities to address the American
      Speech-Language-Hearing Association mandate to universities to convert the entry
      level clinical audiology degree from a master's degree to a clinical doctoral
      (AuD) degree. The Gallaudet AuD program was approved in 1998 and graduated its
      first AuD class in 2002. The purpose of this article is to describe the Gallaudet
      AuD program, the process of converting from a master's program to an AuD program,
      the impact of converting the program, and current challenges. It is hoped that
      this description will be useful to those who are currently developing AuD
      programs.

PMID- 15248799
TI  - Seton Hall university doctor of science degree program: clinical doctorate in
      audiology.
AB  - This article provides an overview of the clinical doctoral program in audiology
      at Seton Hall University. It is a full-time, 4-year program that includes
      academic course work, clinical practica, and research experience. In concert with
      the university mission, the program is designed to enable students to develop the
      skills they need to be leaders in the field of audiology, providing assessment
      and intervention to individuals with hearing problems and enhancing the knowledge
      base of the profession. As part of the School of Graduate Medical Education,
      students in the program have access to a wealth of resources in related health
      professions. The close proximity to New York City provides many opportunities for
      outstanding clinical education with a diverse population.

PMID- 15248800
TI  - Effects of frequency modulation (FM) transmitter microphone directivity on speech
      perception in noise.
AB  - Frequency modulation (FM) technology can significantly improve the speech
      perception ability of individuals with sensorineural hearing loss (SNHL) in
      background noise. Previous investigations have demonstrated that the microphone
      design of the FM transmitter can have a significant impact on this improved
      speech perception. The purpose of this investigation was to compare 3 types of FM
      transmitter microphone designs: (a) wide angle (omnidirectional microphone),
      which amplifies sounds coming from all directions around the microphone equally;
      (b) zoom (1 directional microphone), which provides less amplification to signals
      coming from the rear, and (c) superzoom (2 directional microphones), which
      provides less amplification to signals originating from the rear and the sides.
      Fifteen adults with bilateral slight to moderately severe SNHL participated.
      Speech perception was assessed using the Hearing in Noise Test (M. Nilsson, S.
      Soli, and J. Sullivan, 1994). Speech spectrum shaped noise served as the noise
      competition. Results revealed that the best speech perception in noise was
      obtained when the FM transmitter was used in the zoom setting. The poorest
      performance was obtained when the FM transmitter was in the wide-angle mode. The
      clinical implications of these results are discussed.

PMID- 15248801
TI  - An investigation of list equivalency of the northwestern university auditory test
      no. 6 in interrupted broadband noise.
AB  - The equivalency of Lists 1 to 4 of the Northwestern University Auditory Test No.
      6 (NU-6; T. W. Tillman and R. Carhart, 1966) was investigated in interrupted
      broadband noise. Forty-eight young adults with normal hearing participated. All
      lists were administered at 50 dB sensation level re: listener spondee recognition
      thresholds at signal-to-noise ratios (S/Ns) of 10, 5, 0, -5, -10, -15, -20, -25,
      and -30 dB. Significant differences in listener performance were observed only at
      S/Ns ranging from 10 to -10. Significant mean list differences varied from 5.8%
      to 12.0%. These findings support the notion that caution should be exercised in
      the interpretation of listener performance differences with NU-6 stimuli
      presented in a background of interrupted noise.

PMID- 15248802
TI  - Preschool hearing screening: pass/refer rates for children enrolled in a head
      start program in eastern North Carolina.
AB  - This 4-year project investigated the pass/refer rates of preschool children in a
      hearing screening program. Three- and 4-year-old children who attended Head Start
      centers in rural, traditionally medically underserved, eastern North Carolina
      participated (n = 1,462). Screening procedures and pass/refer criteria were based
      on the Guidelines for Audiologic Screening (American Speech-Language-Hearing
      Association [ASHA], Panel on Audiologic Assessment, 1997). Only 54% (n = 787) of
      children passed the initial screening (i.e., passed all three of the screening
      components, which included pure-tone audiometry, tympanometry, and otoscopy), and
      an additional 22% (n = 323) passed the rescreening, for an overall pass rate of
      76%. The initial pass rate was 90%, 71%, and 71% for otoscopy, tympanometry, and
      pure-tone audiometry, respectively. After the initial screening, 675 children
      were referred (i.e., 83%, 2%, and 15% for audiologic rescreening, medical
      evaluation, or both, respectively). About 71% (n = 478) received the recommended
      evaluation. Follow-up assessment compliance after the rescreening was poor.
      Slightly more than 10% of children were evaluated. The hearing status of 267
      (i.e., 18.3%) children was never determined. Six (i.e., 0.5%) of the 1,195
      children who completed the audiologic screening and/or received diagnostic
      audiologic assessment were confirmed to have hearing loss. Methodological factors
      that may have contributed to this high refer rate include the use of all
      screening techniques (pure tones, tympanometry, and otoscopy), procedural
      considerations in testing protocol and pass/refer criteria, and the demographic
      characteristics of the children screened.

PMID- 15248803
TI  - A comparison of single-channel linear amplification and two-channel wide-dynamic
      range-compression amplification by means of an independent-group design.
AB  - The present study used an independent-group design to compare the benefits
      provided by binaural, single-channel, linear, full-shell in-the-ear hearing aids
      and binaural, 2-channel, wide-dynamic-range-compression in-the-canal hearing aids
      in groups of older hearing aid wearers. Hearing aid outcome measures were
      obtained at both 1-month (n = 53) and 6-month (n = 34) postfit intervals with
      each device. Outcome measures included multiple measures of speech-recognition
      performance and self-report measures of hearing aid benefit, satisfaction, and
      usage. Aided sound-quality measurements were also obtained. Although both devices
      provided significant benefits to the wearers, there were no significant
      differences in the benefits provided by either device at the 1-month or 6-month
      postfit intervals.

PMID- 15248804
TI  - Continuous versus pulsed tones in audiometry.
AB  - The purpose of this study was to compare auditory thresholds obtained for
      continuous and pulsed tones in listeners with normal hearing. Auditory
      thresholds, test-retest reliability, false-positive responses, and listener
      preference were compared for both signals. Hearing thresholds and test-retest
      reliability were comparable for the 2 signals, and there were no significant
      differences in the number of false positives or the number of presentations
      required to reach threshold. Listener preference, however, indicated that pulsed
      tones were preferred over continuous tones by 67% of the listeners when listening
      to low-level or high-frequency tones. These findings, coupled with previous
      reports demonstrating the benefits of using automatically pulsed tones in
      threshold assessment for listeners with tinnitus, support the general use of
      pulsed tones in clinical audiometry.

PMID- 15248805
TI  - Speech perception by students with cochlear implants using sound-field systems in
      classrooms.
AB  - Cochlear implants support deaf students' language development through the
      improved use of audition in the classroom. Unfortunately, the acoustics of
      typical classrooms greatly reduce auditory speech perception by these students.
      Sound-field systems can increase speech-to-noise ratios in classrooms and thus
      improve use of audition. These systems are used by 80% of students with cochlear
      implants who use an FM system in the classroom. The present study compares speech
      perception by 14 school-age cochlear implant recipients via 2 classroom sound
      field systems, 1 wall-mounted and the other a personal, or desktop, system.
      Testing was conducted in 2 classroom environments, 1 noisy and reverberant
      (typical of many classrooms) and the other ideally quiet with reverberation of
      short duration. In the quiet room with low reverberation, both sound-field
      systems produced improved phoneme recognition, but there was no difference
      between the 2. In the noisy room with high reverberation, the sound-field
      benefits were greater, and the desktop systems provided more benefit than the
      wall-mounted systems.

PMID- 15248806
TI  - Evaluation of an adaptive directional system in a DSP hearing aid.
AB  - The effectiveness of an adaptive directional microphone design, as implemented in
      the Phonak Claro behind-the-ear hearing aid, is evaluated. Participants were fit
      bilaterally and tested in 2 environments, an anechoic chamber and a moderately
      reverberant classroom, with the microphones in the fixed (cardioid) setting and
      the adaptive setting. Five speakers were placed between 110 degrees and 250
      degrees azimuth around the listener. Speech-weighted noise was presented from
      those speakers at an overall level (OAL) of 65 dB (A). Noise was increased by 8
      dB from 1 speaker at a time, using 2-s modulation and random assignment, while
      the output from the other speakers was reduced to maintain the constant OAL.
      Results of 2 speech perception tasks used as outcome measures indicated that the
      adaptive system was not able to follow the dominant noise source in the presence
      of lower level noise sources. Self-report measures obtained after blinded home
      trials were consistent with laboratory findings that the participants did not
      perceive this adaptive microphone design to be more effective than the default
      fixed-microphone option.

PMID- 15248807
TI  - Interference and enhancement effects on interaural time discrimination and level
      discrimination in listeners with normal hearing and those with hearing loss.
AB  - It is known that many listeners with sensorineural hearing loss (SNHL) have
      difficulty performing binaural tasks. In this study, interference and enhancement
      effects on interaural time discrimination and level discrimination were
      investigated in 4 listeners with normal hearing (NH) and 7 listeners with SNHL.
      Just-noticeable differences were measured using 1/3-octave narrowband noises
      centered at 0.5 and 4 kHz. Noises were presented in isolation and together at
      equivalent sound pressure level (EqSPL) and equivalent sensation level (EqSL).
      Each noise served as target and distractor in the dual-band conditions. Congruent
      conditions included interaural differences in both noises that varied together,
      and incongruent conditions included an interaural difference in one noise with
      the second noise diotic. No significant enhancement effects were observed for
      either group in either task. Interference effects for the NH group were limited
      to the interaural level discrimination task in the 0.5-kHz target and 4-kHz
      distractor condition. Performance of participants with SNHL was similar to that
      of the NH group for interaural time discrimination with noises at EqSL but not
      EqSPL. In interaural level discrimination, listeners with SNHL demonstrated
      interference with a 4-kHz target and 0.5-kHz distractor. Results indicated that
      the relative levels of low- and high-frequency targets and distractors could
      affect binaural performance of individuals with SNHL but that in some conditions
      listeners with SNHL performed similarly to those with normal hearing.
      Implications of these results for binaural clinical tests and hearing aid fitting
      strategies are discussed.

PMID- 15248808
TI  - Amorphous drug delivery systems: molecular aspects, design, and performance.
AB  - The biopharmaceutical properties-especially the solubility and permeability-of a
      molecule contribute to its overall therapeutic efficacy. The newer tools of drug
      discovery have caused a shift in the properties of drug-like compounds, resulting
      in drugs with poor aqueous solubility and permeability, which offer delivery
      challenges, thus requiring considerable pharmaceutical manning. The modulation of
      solubility is a more viable option for enhancing bioavailability than
      permeability, because of the lack of "safe" approaches to enhance the latter.
      Solid-state manipulation in general, and amorphization in particular, are
      preferred ways of enhancing solubility and optimizing delivery of poorly soluble
      drugs. This review attempts to address the diverse issues pertaining to amorphous
      drug delivery systems. We discuss the various thermodynamic phenomenon such as
      glass transition, fragility, molecular mobility, devitrification kinetics, and
      molecular-level chemical interactions that contribute to the ease of formation,
      the solubility advantage, and the stability of amorphous drugs. The engineering
      of pharmaceutical alloys by solubilizing and stabilizing carriers, commonly
      termed solid dispersions, provide avenues for exploiting the benefits of
      amorphous systems. Carrier properties, mechanisms of drug release, and study of
      release kinetics help to improve the predictability of performance. The review
      also addresses the various barriers in the design of amorphous delivery systems,
      use of amorphous form in controlled release delivery systems, and their in vivo
      performance.

PMID- 15248809
TI  - Mucosal drug delivery: membranes, methodologies, and applications.
AB  - In recent years, extensive research into novel forms of drug delivery has
      suggested that mucosal approaches offer a promising therapeutic alternative,
      especially for systemically acting drugs. Transmucosal drug delivery offers many
      benefits, including noninvasive administration, convenience, rapid onset, as well
      as elimination of hepatic first-pass metabolism. The investigated absorptive
      surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among
      these, the nasal and buccal routes have proved the most promising to date. The
      bioavailability achieved mainly depends upon the pathophysiological state of the
      mucosa and the properties of both the drug and delivery systems. Various agents
      can increase the efficacy of transmucosal drug delivery. These include
      cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres,
      liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and
      toxicity profiles of these enhancers have been investigated extensively in both
      animal and human models.

PMID- 15248810
TI  - Botulinum neurotoxin: the neuromuscular junction revisited.
AB  - Botulinum neurotoxin is the neuromuscular poison that is responsible for the
      fatal disease botulism. This toxin is also a valued therapeutic agent in the
      treatment of an increasing number of neuromuscular disorders. Unfortunately, in
      the wrong hands, botulinum neurotoxin is also a deadly biological "weapon. The
      diverse health consequences of botulinum neurotoxin combined with the increased
      threat of bioterrorism underscore the profound importance of understanding
      exactly how this toxin exerts its effects on the clinically relevant mammalian
      target site, the neuromuscular junction. Despite the fact that a great deal has
      been learned about the cellular actions of botulinum neurotoxin during the past
      three decades, questions still remain. For example, what protein or proteins
      mediate transport of the toxin into the cholinergic nerve terminal? What factors
      control the duration of toxin action in the nerve terminal? Until recently,
      scholarly pursuit of such questions was technically challenging in neuromuscular
      tissues. Recent advancements in biotechnology have now made it feasible to pursue
      these important issues at the neuromuscular junction and to correlate biochemical
      studies in nontarget tissues with clinically relevant functional outcomes. This
      narrative reviews our current understanding of the actions of botulinum
      neurotoxin at the neuromuscular junction, presents recent findings from our own
      work in neuromuscular tissues, and encourages future studies regarding botulinum
      neurotoxin at its target site.

PMID- 15248811
TI  - Pharmacology of endogenous neuroactive steroids.
AB  - Neuroactive steroids are potent endogenous neuromodulators with rapid actions in
      the central nervous system. Neuroactive steroids have been claimed to have
      specific physiological roles in normal or pathological brain function. This
      article reviews the emerging evidence that progesterone-, deoxycorticosterone-,
      and testosterone-derived endogenous neuroactive steroids play an important role
      in the modulation of neural excitability and brain function. Neuroactive steroids
      such as allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC) are
      extremely potent positive allosteric modulators of GABAA receptors with sedative,
      anxiolytic, and anticonvulsant properties. The sulfated neuroactive steroids
      pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS), which are
      negative GABAA receptor modulators, induce anxiogenic and proconvulsant effects.
      Thus, natural fluctuations in neuroactive steroid levels during the menstrual
      cycle and stress could affect several nervous system functions. There is strong
      evidence that allopregnanolone and THDOC are involved in the pathophysiology of
      premenstrual syndrome, catamenial epilepsy, major depression, and stress
      sensitive brain disorders. Neuroactive steroids PS and DHEAS have been shown to
      modulate memory functions. However, the significance of the testosterone-derived
      neuroactive steroid 3alpha-androstanediol is not well understood. Like naturally
      occurring neuroactive steroids, synthetic derivatives such as ganaxolone have
      been proven in preclinical and clinical studies to be effective anticonvulsants
      with great potential for human use. Future research on inhibition or stimulation
      of specific neuroactive steroid synthesizing enzymes could provide an improved
      understanding and novel approaches for the treatment of anxiety, epilepsy, and
      depression.

PMID- 15248812
TI  - Adaptations in adenosine signaling in drug dependence: therapeutic implications.
AB  - Adenosine is an important endogenous purine neuromodulator in the central nervous
      system that modulates many important cellular processes in neurons. The
      physiological effects of adenosine are transduced through four pharmacologically
      classified receptor types i.e., A1, A2A, A2B and A3. All adenosine receptors are
      G-protein coupled receptors (GPCR) of the type 1 variety. Adaptations in
      adenosine signaling have been implicated in a wide range of pathophysiological
      processes, such as epilepsies, sleep disorders, pain, and drug addictions.
      Knowledge relating to the etiology of addictive processes is far from complete,
      and as a result the therapeutic options to deal with drug dependence issues are
      limited. Drugs of abuse mediate their effects through many distinct cellular
      effectors, such as neurotransmitter transporters, ion channels, and receptor
      proteins. However, a unifying feature of the major drugs of abuse-i.e., opiates,
      cocaine, and alcohol-is that they all directly or indirectly modulate adenosine
      signaling in neurons. Agents targeting adenosine receptors may therefore offer
      novel avenues for the development of therapies to manage or treat addictions. A
      consistent cellular adaptation to long-term drug use is the up- or down
      regulation of signaling pathways driven by adenylyl cyclase/cyclic AMP (cAMP) in
      several brain regions linked to addiction. Withdrawal from mu-opioids or cocaine
      following their chronic administration leads to an upregulation of adenylyl
      cyclase-mediated signaling, resulting in high levels of cAMP. Cyclic AMP produced
      in this way acts as a substrate for the endogenous production of adenosine.
      Increased levels of endogenous adenosine interact with presynaptic A1 receptors
      to inhibit the excessive neuronal excitation often seen during morphine/cocaine
      withdrawal. These pre-clinical findings fit well with other data indicating that
      drugs which boost endogenous adenosine levels or directly interact with
      inhibitory A1 receptors can alleviate many of the negative consequences of
      opioid/cocaine withdrawal. Ethanol interacts directly with the adenosine system
      by blocking nucleoside transporters in the cell membrane. The effect of this
      inhibition is an increase in extracellular adenosine levels and adenosine
      receptor activation. Depending on the time course of ethanol exposure and the
      receptor population present, cAMP levels are either reduced or increased. Chronic
      ethanol treatment tends to reduce cAMP levels as a consequence of the
      desensitization of stimulatory GPCRs (such as A2-type receptors) seen following
      prolonged receptor activation. Unlike opiates and cocaine, adenosine receptor
      activation worsens the behavioral effects of drug ingestion, and evidence
      indicates that agents that negatively modulate adenosine receptor function have
      some utility in attenuating the effects of ethanol use. Taken together, these
      data suggest that pharmacological manipulation of adenosine signaling represents
      a potentially useful means of managing drug dependence.

PMID- 15248813
TI  - Structure and function of histone methyltransferases.
AB  - Histones are the major protein constituent of chromatin in the eukaryotic
      nucleus. These proteins undergo a host of different post-translational
      modifications, including phosphorylation, acetylation, and methylation, which
      have profound effects on the remodeling of chromatin. Histone modifications can
      function either individually or combinatorially to govern such processes as
      transcription, replication, DNA repair, and apoptosis. Recent studies have
      focused on histone arginine and lysine methylation and the roles of these
      modifications in transcriptional regulation and the establishment of
      heterochromatin. Concomitantly, several families of histone methyltransferases
      (HMTs) have been identified that catalyze the methylation of specific arginines
      or lysines in histones H3 and H4. Not surprisingly, many of these
      methyltransferase genes had been previously identified as important genetic
      regulators in organisms such as yeast and Drosophila, which underscores the
      importance of histone methylation in transcriptional control and chromatin
      remodeling. Structures of several representatives of these HMT families have
      recently been determined, yielding insight into their catalytic mechanism and
      histone substrate specificity. The focus of this review is to briefly summarize
      the roles of histone methylation in chromatin remodeling and to discuss the
      structures, substrate specificities, and mechanisms of the different classes of
      HMTs.

PMID- 15248814
TI  - Sp1 control of gene expression in myeloid cells.
AB  - Gene transcription plays a critical role in the differentiation of myeloid cells.
      However, there is no single, master regulator of all myeloid genes. Rather,
      myeloid gene transcription is regulated by the combinatorial effects of a limited
      number of key transcription factors. Sp1 is a powerful activator of gene
      transcription in many cell types. Although it is wildly expressed, Sp1 binds and
      activates the promoters of a large number of important myeloid genes. This
      presents the paradox of how a widely expressed transcription factor can regulate
      lineage-specific gene transcription. This review discusses the structure,
      function, and expression patterns of Sp1 and its related Sp family members.
      Illustrative examples of the tissue-specific regulation of myeloid target genes
      are presented. The roles of post-translational modifications of Sp1, alterations
      in target gene chromatin structure, and important cooperating transcription
      factors are discussed. Thus, Sp1 serves as a model of how a widely expressed
      transcription factor regulates the expression of tissue-specific genes.

PMID- 15248815
TI  - Regulation of cell cycle progression and apoptosis by the papillomavirus E6
      oncogene.
AB  - Infection with human papillomaviruses (HPV) is strongly associated with the
      development of cervical cancer. The HPV E6 gene is essential for the oncogenic
      potential of HPV. E6 abrogates multiple cell cycle checkpoints and modulates
      apoptosis. Loss of cell cycle checkpoints contributes to genomic instability, a
      hallmark of cancer cells. Cancer cells also show reduced propensity for apoptotic
      cell death. Inactivation of the tumor suppressor p53 by E6 is an important
      mechanism by which E6 promotes cell growth. The molecular basis for apoptosis
      modulation by E6 is poorly understood. Although it is expected that inactivation
      of p53 by E6 should lead to a reduction in cellular apoptosis, numerous studies
      showed that E6 could in fact sensitize cells to apoptosis. In this article, we
      present an overview of observations and current understanding of the molecular
      basis for E6-induced cell proliferation and apoptosis.

PMID- 15248816
TI  - The regulated synthesis of versican, decorin, and biglycan: extracellular matrix
      proteoglycans that influence cellular phenotype.
AB  - The principal extracellular matrix (ECM) chondroitin/dermatan sulfate
      proteoglycans include members of two gene families--the large aggregating
      chondroitin sulfate proteoglycans (lecticans) and the small leucine-rich
      proteoglycans (SLRPs). These families of proteoglycans are widely distributed
      within the interstitial matrix, where they are known to bind a variety of both
      soluble and insoluble ligands. Extensive structural studies and data concerning
      the synthesis of these proteoglycans have been published over the last few years.
      This review focuses on the regulation of the expression of the lectican,
      versican, and the SLRPs--decorin and biglycan, as well--studied and widely
      distributed examples of these families of ECM proteoglycans. In addition, the
      effects of these proteoglycans on the formation of the ECM and the response of
      cells to growth factors and cytokines are examined as mechanisms by which
      versican, decorin and biglycan, both directly and indirectly influence cellular
      proliferation, migration, and phenotype.

PMID- 15248817
TI  - Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of
      human studies.
AB  - The age-related decline in serum dehydroepiandrosterone (DHEA) and its sulfated
      ester (DHEA-S) has suggested that a relative deficiency of these steroids may be
      causally related to the development of chronic diseases generally associated with
      aging, including insulin resistance, obesity, cardiovascular disease, cancer,
      reductions of the immune defense, depression and a general deterioration in the
      sensation of well-being. The numerous studies which have focused on the link
      between DHEA and cardiovascular disease have generally been inconsistent,
      generating much debate and controversy on this issue. The present article is an
      analysis of studies on the relationship between endogenous DHEA or DHEA-S,
      obesity and cardiovascular disease risk, as well as DHEA treatment studies.
      Elevated plasma levels of free DHEA are associated with reduced obesity in both
      men and women, and with smaller abdominal body fat accumulations in men. However,
      contradictory results have been reported regarding the relationships between the
      sulfate ester DHEA-S and adiposity. Age differences in the populations studied
      may have been a confounding factor in these associations. On the other hand, DHEA
      S level is not a predictor of cardiovascular disease endpoints in women, and
      appears to be a relatively weak one in men. DHEA intervention studies suggest
      that the effects of DHEA on serum lipids are, at best, modest or non-significant.
      The uncertainty as to whether endogenous and exogenous DHEA should be considered
      cardioprotective is related to discrepancies in the literature on this topic.
      Several studies may have been plagued by methodological problems such as low
      power, unreliable analytical methods, confounding factors or other differences in
      the populations studied. As a consequence, the original reports demonstrating
      dramatic effects of either endogenous or exogenous DHEA on cardiovascular disease
      risk have never been replicated. We propose that the effects of DHEA on
      cardiovascular disease risk (either favorable or unfavorable) should be
      considered to be much more modest than previously believed.

PMID- 15248818
TI  - Recent advances in radiological and radionuclide imaging and therapy of
      neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that
      are able to express cell membrane neuroamine uptake mechanisms and/or specific
      receptors, such as somatostatin receptors, which can be of great value in the
      localization and treatment of these tumours. Scintigraphy with (111)In
      pentetreotide has become one of the most important imaging investigations in the
      initial identification and staging of gastro-enteropancreatic (GEP) tumours,
      whereas helical computed tomography (CT), magnetic resonance imaging (MRI),
      endoscopic and/or peri-operative ultrasonography are used for the precise
      localization of GEPs and in monitoring their response to treatment. Scintigraphy
      with (123)I-MIBG (meta-iodobenzylguanidine) is sensitive in the identification of
      chromaffin cell tumours, although scintigraphy with (111)In-pentetreotide may
      also have a role in the localization of malignant chromaffin cell tumours and
      medullary thyroid carcinoma; for further localization and monitoring of the
      response to treatment both CT and MRI are used with high diagnostic accuracy.
      More recently, positron emission tomography (PET) scanning is being increasingly
      used for the localization of NETs, particularly when other imaging modalities
      have failed, although its precise role and utility remain to be defined. Surgery
      is still the usual initial therapeutic, and only curative, modality of choice;
      however, the majority of NETs will require further treatment with somatostatin
      analogues and/or interferon; chemotherapy may be used for progressive and highly
      aggressive NETs, but its role has not been clearly defined. For those NETs that
      demonstrate uptake to a diagnostic scan with (123)I-MIBG or (111)In-octreotide,
      therapy with radionuclides such as (131)I-MIBG or (111)In/(90)Y-octreotide or
      other isotopes, presents a further evolving therapeutic modality.

PMID- 15248819
TI  - The influence of testosterone upon vascular reactivity.
AB  - Recent clinical studies have reported that testosterone therapy reduces
      myocardial ischaemia in men with coronary artery disease, and the beneficial
      modulation of coronary vascular tone by testosterone has been proposed as an
      effector mechanism. Maintenance of a correct response to vasoconstrictive and
      vasodilatory agents is essential in the control of vascular tone. Endothelial
      dysfunction, most commonly manifested through an elevation in vascular tone, is
      implicated as an initiating factor in conditions such as hypertension and
      atherosclerosis. Increased sensitivity to vasoconstrictive stimuli is also
      proposed in the development of heart failure and hypertensive vascular
      remodelling, while increased coronary vascular reactivity to vasoconstrictive
      factors is likely further to restrict coronary blood flow through the partially
      occluded atherosclerotic vessel. Reduced vasodilatation and enhanced
      vasoconstriction can also lead to vasospasm and exacerbation of anginal symptoms.
      Testosterone is well known to elicit direct vasodilatation, but its influence
      upon responses induced by other vasoactive agents is less coherent, and may
      depend upon the underlying pathogenic process or gender. The aim of this review
      is to present the data obtained from both the patient and animal studies
      conducted to date, to ascertain any influence testosterone may have upon the
      regulation of vascular tone.

PMID- 15248820
TI  - Short-term low-dose growth hormone administration in subjects with impaired
      glucose tolerance and the metabolic syndrome: effects on beta-cell function and
      post-load glucose tolerance.
AB  - OBJECTIVE: Modest elevations in circulating IGF-I levels have been suggested to
      protect against the development of glucose intolerance in insulin-resistant
      subjects. To further understand the interactions of GH and IGF-I on beta-cell
      function and post-load glucose tolerance in glucose-intolerant subjects
      predisposed to diabetes, we performed a pilot study in 12 subjects with impaired
      glucose tolerance and the metabolic syndrome using a low GH dose (1.7 microg/kg
      per day) known to increase endogenous IGF-I production. DESIGN: Fourteen daily GH
      or placebo injections in a double-blind cross-over study. METHODS: Baseline and
      post-treatment oral glucose tolerance tests were performed. The homeostasis model
      assessment and the insulinogenic index was used to estimate fasting insulin
      sensitivity (S(I)) and beta-cell function respectively, whereas changes in the
      incremental area under the curve were used to estimate post-load glucose
      tolerance (DeltaAUC(glu)) and post-load insulin levels (DeltaAUC(ins)). RESULTS:
      GH increased total IGF-I (P<0.02), free IGF-I (P<0.04) and fasting insulin
      (P<0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and 
      3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting
      S(I). After oral glucose intake, glucose tolerance improved (P<0.03), but post
      load insulin levels and beta-cell function remained unchanged. CONCLUSION: Short
      term low-dose GH administration induced fasting hyperinsulinaemia possibly by
      reducing insulin clearance but improved post-load glucose tolerance, suggesting
      that increased bioavailable IGF-I enhanced post-load S(I) without altering beta
      cell function. Longer-term studies are required to ascertain whether these
      positive effects on post-load glucose tolerance and the preservation of beta-cell
      function can be sustained by this GH dose in these high-risk subjects.

PMID- 15248821
TI  - Selenium substitution has no direct effect on thyroid hormone metabolism in
      critically ill patients.
AB  - BACKGROUND: In severe illness, plasma selenium levels are decreased; a decreased
      activity of the selenoenzyme 5'-deiodinase has been hypothesized to contribute to
      low tri-iodothyronine (T3) levels in non-thyroidal illness (NTI) syndrome in
      these patients. OBJECTIVE: To analyse the influence of selenium substitution on
      thyroid hormone metabolism in patients with severe sepsis. DESIGN: A prospective,
      randomized, controlled study at the medical internal intensive care unit of the
      University of Munich. Results are for 41 consecutive patients with severe sepsis
      with an APACHE II score >15. Patients received either sodium selenite (500
      microg/day for the first 3 days, reducing to 250 and then 125 microg/day every 3
      days) or a placebo. RESULTS: At study entry, APACHE II score and demographics
      were identical in both groups. The mean levels of TSH, free tri-iodithyronine and
      total T3, as well as plasma selenium and selenium-dependent peroxidase (GSH-Px)
      activity, were decreased. Plasma selenium and GSH-Px activity were normalized on
      days 3, 7 and 14 in patients receiving selenium (n=21), but remained below normal
      in the control patients. Patients receiving selenium had a better clinical
      outcome and thyroid hormone levels normalized earlier. Thyroid hormone levels
      increased in patients who showed clinical improvement, independent of selenium
      levels or selenium substitution. CONCLUSIONS: Selenium substitution in patients
      with NTI improves morbidity, but has no direct effect on the free and total
      thyroid hormones. In severely ill patients, decreased deiodinase activity due to
      low plasma selenium levels seems unlikely. After clinical revival, TSH and then
      the thyroidal hormones normalize independently of selenium substitution.

PMID- 15248822
TI  - Fibroblast growth factor (FGF)-23 in patients with primary hyperparathyroidism.
AB  - OBJECTIVE: We aimed to determine the serum level of fibroblast growth factor-23
      (FGF-23) in patients with primary hyperparathyroidism (pHPT) to understand its
      physiological role in the disorder. PATIENTS AND METHODS: Ninety-eight patients
      with pHPT who underwent parathyroidectomy formed the study group. We also
      measured serum FGF-23 in 11 of these patients on postoperative day 6. RESULTS:
      Serum FGF-23 levels was significantly higher in pHPT patients than in healthy
      controls (35.6+/-17.8 ng/l vs 28.9+/-11.2 ng/l (mean+/-s.d.); P<0.001 (Pearson's
      correlation coefficient)), but there was no significant difference in the serum
      FGF-23 level between pHPT patients with normal renal function (creatinine
      clearance (Ccr) of >or=70 ml/min) and healthy controls. Serum FGF-23 correlated
      positively with serum calcium (P<0.0001) and intact parathyroid hormone (PTH)
      (P<0.01), and negatively with Ccr (P<0.001), serum phosphate (P<0.05), and serum
      1,25-dihydroxyvitamin D (1,25(OH)(2)D) (P<0.05). Multiple linear regression
      analysis of factors potentially determining serum FGF-23 levels in pHPT patients
      showed serum calcium (P<0.01) and Ccr (P<0.001) to be significant predictors. The
      serum levels of FGF-23 did not change after parathyroidectomy despite the
      normalization of serum calcium values. Multiple linear regression analysis
      revealed that serum FGF-23 was not a significant predictor of serum phosphate or
      1,25(OH)(2)D in pHPT patients. CONCLUSIONS: FGF-23 may not play a significant
      role in regulating phosphate or 1,25(OH)(2)D in pHPT patients, especially in
      those with normal renal function. Further studies are warranted to determine the
      role of FGF-23 in renal insufficiency or failure.

PMID- 15248823
TI  - Life events in the pathogenesis of hyperprolactinemia.
AB  - OBJECTIVE: Little is known about the relationship between recent life events and
      onset of hyperprolactinemia, despite the well-known effect of acute psychological
      stress on prolactin levels in healthy subjects. Recent life events in patients
      with hyperprolactinemia compared with healthy controls were investigated. DESIGN:
      Case-control study. METHODS: Fifty-two consecutive patients with
      hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60
      years) and 52 healthy subjects matched for socio-demographic variables were
      studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were
      diagnosed as suffering from idiopathic hyperprolactinemia. Patients with
      additional pathology or with high prolactin due to medications were excluded. All
      patients were interviewed by Paykel Interview for Recent Life Events while on
      remission after surgery or pharmacological treatment. The time period considered
      was the year preceding the first signs of hyperprolactinemia, and the year before
      interview for controls. RESULTS: Patients with hyperprolactinemia reported
      significantly more life events than control subjects (P<0.001). The same
      significant difference compared with controls applied to patients with (n=16) and
      without (n=36) depression. All categories of events (except events that were
      likely to be under the subject's control) were significantly more frequent. There
      were no significant differences between patients with prolactinoma (n=33) and
      those with idiopathic hyperprolactinemia (n=19). CONCLUSIONS: Within the
      complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our
      findings emphasize a potential role of emotional stress in either prolactin
      secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life
      stress may have implications in clinical assessment (e.g. functional
      hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological
      treatment).

PMID- 15248824
TI  - Prevalence and demographic features of childhood growth hormone deficiency in
      Belgium during the period 1986-2001.
AB  - OBJECTIVE: Since the availability of recombinant human growth hormone (rhGH) all
      children with growth hormone deficiency (GHD) living in Belgium are offered rhGH
      treatment after approval by a peer-review board. In this study, we evaluated the
      prevalence and demographic features of childhood GHD in Belgium during the period
      1986-2001 and we compared them with the data from other countries. METHODS:
      Diagnostic, demographic and baseline auxological data of 714 children diagnosed
      as having GHD between 1986 and 2001 were retrieved from the database of the
      Belgian Study Group for Paediatric Endocrinology. RESULTS: The prevalence of GHD
      in Belgium was estimated to be 1/5600. The origin of GHD was idiopathic (idGHD)
      in 41% of the patients, congenital (congGHD) in 20% and acquired (acqGHD) in 35%.
      During the first 4 years (1986-1989) more patients were classified as idGHD;
      thereafter the distribution between the three aetiology groups did not change. In
      all groups, boys outnumbered girls but this preponderance was especially
      pronounced in congGHD patients (male:female=4:1) with a central malformation that
      associates an anterior pituitary hypoplasia, a missing, fine or normal pituitary
      stalk and an ectopic posterior pituitary. Thirteen percent of the patients with
      idGHD, 50% with congGHD and 52% with acqGHD had multiple pituitary deficiencies.
      Patients with congGHD were the youngest (mean+/-s.d. age: 6.5+/-4.7 years) and
      were the shortest (-3.0+/-1.3 standard deviation score (SDS)) at the start of
      rhGH treatment. There was no time trend over the studied period for age and
      height at onset of GH therapy. CONCLUSION: In Belgium, the prevalence of
      childhood GHD can be estimated as 1/5600 which is comparable to other recent
      surveys. The yearly number of new patients for the different aetiologies and the
      auxological parameters have remained relatively constant over the last 16 years.

PMID- 15248825
TI  - Postoperative differentiation between unilateral adrenal adenoma and bilateral
      adrenal hyperplasia in primary aldosteronism by mRNA expression of the gene
      CYP11B2.
AB  - OBJECTIVE: Primary aldosteronism (PA) is characterized by hypertension,
      hypokalemia and suppressed renin-angiotensin system caused by autonomous
      aldosterone production. The aim of this study was to localize mRNA expression of
      the genes coding for steroidogenic enzymes in adrenals from a group of patients
      with PA and relate this to clinical work-up, histopathology and outcome of
      adrenalectomy. DESIGN: This was a retrospective study of 27 patients subjected to
      adrenalectomy for PA. METHODS: Clinical data were collected and follow-up of all
      patients was performed. Paraffin-embedded specimens were analyzed by the in situ
      hybridization technique, with oligonucleotide probes coding for the steroidogenic
      enzyme genes. RESULTS: The resected adrenals had the histopathologic diagnosis of
      adenoma (11), adenoma and/or hyperplasia (15) or hyperplasia (1). CYP11B2
      expression (indicating aldosterone production) was found in a dominant adrenal
      nodule from 22 patients. Fourteen of these had additional CYP11B2 expression in
      the zona glomerulosa. All 22 patients were cured of PA by adrenalectomy. One of
      these patients, who had additional high expression of CYP11B2 in the zona
      glomerulosa, was initially cured, but the condition had recurred at follow-up.
      Two patients had a mass shown on computed tomography without CYP11B2 but with
      CYP11B1 and CYP17 expression (indicating cortisol production). Instead their
      adrenals contained small nodules with CYP11B2 expression. These patients were not
      cured. CONCLUSIONS: Clinical data, endocrinologic evaluation and histopathology
      in combination with mRNA in situ hybridization of steroidogenic enzyme genes
      provide improved opportunities for correct subclassification postoperatively of
      patients with primary aldosteronism. At present, the in situ hybridization method
      is of special value for analysis of cases not cured by adrenalectomy.

PMID- 15248826
TI  - Intrafollicular expression of matrix metalloproteinases and their inhibitors in
      normally ovulating women compared with patients undergoing in vitro fertilization
      treatment.
AB  - OBJECTIVE: To assess possible differences in the activity of matrix
      metalloproteinases (MMPs), MMP-2 and MMP-9, and their inhibitors, the tissue
      inhibitors of MMPs, TIMP-1 and TIMP-2, in follicular fluid (FF) of women
      undergoing in vitro fertilization (IVF) treatment and of normally ovulating
      women. DESIGN: Prospective study. METHODS: MMP-2 and MMP-9 activity was analyzed
      by gelatin zymography and MMP-2, MMP-9, TIMP-2, TIMP-1 and 17beta-estradiol
      levels were measured in FF by ELISA. RESULTS: We found significantly reduced MMP
      levels in FF of women undergoing IVF treatment when compared with those of
      normally ovulating women. In contrast, the TIMP-1 levels were found significantly
      increased in FF from IVF patients vs normally ovulating women. No significant
      differences were found for TIMP-2 between the two groups. CONCLUSIONS: These
      findings underline a marked difference in MMPs and their inhibitors in the IVF
      women and the control group. Therefore we assume MMPs depend on hormonal
      steroidogenesis modulation induced by the gonadotropin protocol for IVF
      treatment.

PMID- 15248827
TI  - Changes in the expression and cytological localization of betacellulin and its
      receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the
      course of pregnancy.
AB  - OBJECTIVE: Betacellulin (BTC), purified and cloned from mouse beta cell tumor
      (BTC-JC10), is regarded as a new member of the epidermal growth factor family.
      The present study was conducted to clarify the expression of BTC and its
      receptors, ErbB-1 and ErbB-4, in the trophoblasts in the human placenta over the
      course of pregnancy. DESIGN AND METHODS: Human placental tissues were obtained
      from 4 pregnant women at the 4th to 5th week of pregnancy (very early placentas),
      10 women at the 6th to 12th week (early placentas), 5 women at the 18th to 21st
      week (mid placentas) and 8 women at the 38th and 40th week (term placentas). The
      mRNA expressions of BTC, erbB-1 and erbB-4 were evaluated by quantitative RT-PCR
      with Southern blotting and the expression of the soluble form of BTC was
      determined by western immunoblot with a specific antibody to BTC protein.
      Immunohistochemical staining of BTC, ErbB-1 and ErbB-4 was also performed.
      RESULTS: The levels of BTC mRNA expression in early and mid placentas were
      significantly higher than those in term placentas. The soluble form of BTC
      protein with an estimated molecular mass of 9.5 kDa was expressed in early and
      mid placentas, whereas the soluble form was not detected in term placentas. BTC
      from very early placentas until mid placentas was immunolocalized in
      syncytiotrophoblasts (S-cells), and was most abundant in early placentas. In
      contrast, BTC was immunolocalized in extravillous trophoblasts (EVTs), but not in
      villous trophoblasts in term placentas. The levels of erbB-1 mRNA in the early
      and mid placentas were significantly higher than those in term placentas, whereas
      the levels of erbB-4 mRNA in early placentas were significantly lower than those
      in mid and term placentas. ErbB-1 was immunolocalized in cytotrophoblasts in very
      early placentas, whereas it was immunolocalized in S-cells from early until term
      placentas. ErbB-4 from very early placentas until mid placentas was
      immunolocalized in S-cells, whereas ErbB-4 in the term placentas was detected in
      EVTs, but not in villous trophoblasts. CONCLUSIONS: These findings provide
      evidence for changes in expression and cytological localization of BTC and its
      receptors in the trophoblasts in human placenta over the course of pregnancy. BTC
      may play a pivotal role as a local growth factor in promoting the differentiated
      villous trophoblastic function via ErbB-1 in early placentas and in contributing
      to placental growth through the maintenance of EVT cell function via ErbB-4 in
      term placentas.

PMID- 15248828
TI  - Diabetic retinopathy in two patients with congenital IGF-I deficiency (Laron
      syndrome).
AB  - OBJECTIVE: Animal and clinical studies have shown that excessive amounts of
      growth hormone or insulin-like growth factor-I (IGF-I) promote the development of
      diabetes and diabetic retinopathy. Forthwith, we present two patients with
      congenital IGF-I deficiency who developed type II diabetes and subsequently
      retinopathy. METHODS: Eighteen adult patients with classical Laron syndrome (8
      males, 10 females, aged 20-62 years) were followed by us since childhood or
      underwent fundus photography with a Nikon NF 505 instrument. Three had been
      treated in childhood with IGF-I, the rest were never treated, including the two
      patients reported. RESULTS: Two never-treated patients were diagnosed with type
      II diabetes (DM) at ages 39 and 41 respectively. There was no diabetes in the
      families. Oral treatment was followed by insulin injections. Metabolic control
      was not optimal and one patient developed proliferative diabetic retinopathy,
      necessitating laser surgery. He also has nephropathy and severe neuropathy. The
      other patient has background diabetic retinopathy and has developed,
      progressively, exudates, microaneurisms, hemorrhages and clinically significant
      macular edema. He also has subacute ischemic heart disease. CONCLUSIONS: Our
      findings show that congenital IGF-I deficiency, similar to excess, causes
      vascular complications of DM, denoting also that vascular endothelial growth
      factor can induce neovascularization in the presence of congenital IGF-I
      deficiency.

PMID- 15248829
TI  - High-dose treatment with a long-acting somatostatin analogue in patients with
      advanced midgut carcinoid tumours.
AB  - OBJECTIVE: High-dose somatostatin analogue treatment has shown an
      antiproliferative effect in one study including patients with neuroendocrine
      tumours. To explore this therapeutic strategy further, we have studied the effect
      of a high-dose formula of octreotide, octreotide pamoate, in midgut carcinoid
      patients. DESIGN AND METHODS: Twelve patients with advanced midgut carcinoid
      tumours with a median duration of disease of more than 5 years were included. All
      were in a progressive state despite several previous treatment modalities.
      Octreotide pamoate (160 mg) was given as an intramuscular injection every 2 weeks
      for 2 months and then monthly. Radiological and biochemical responses were
      monitored. RESULTS: Tumour size and biochemical markers were stabilised for a
      median of 12 months in 75% of the patients. Ten patients had symptomatic
      improvement of flush and diarrhoea. CONCLUSION: In this group of patients with
      advanced midgut carcinoid tumours and progressive disease, octreotide pamoate
      managed to improve symptoms, and stabilise hormone production and tumour growth
      in 75% of the patients. We believe that high-dose treatment with somatostatin
      analogues can be an important addition to the therapeutic arsenal for patients
      with advanced progressive midgut carcinoid tumours.

PMID- 15248830
TI  - Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.
AB  - OBJECTIVE: The orexigenic and adipogenic peptide hormone ghrelin is predominantly
      produced and secreted by the stomach and seems to transduce changes in food
      intake to specific neuronal circuits in the brain. The activity of ghrelin also
      includes stimulatory effects on the corticotropic system. However, little is
      known about the influence of glucocorticoids on ghrelin levels. We therefore
      studied human plasma ghrelin levels in the presence and absence of elevated
      glucocorticoid levels of either endogenous or exogenous origin. METHODS: Plasma
      ghrelin levels were measured in five patients with chronic hypercortisolism (aged
      29-58, median 46 years) due to Cushing's syndrome before and after successful
      surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5
      years) before and after 30 mg prednisolone (for 5 days) once a day in the morning
      (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured
      with a commercially available radioimmunoassay. RESULTS: In patients with
      Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range
      161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful
      surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong
      negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin
      was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml,
      range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after
      prednisolone treatment. CONCLUSIONS: We have shown for the first time that plasma
      ghrelin levels are decreased under endogenously or exogenously induced
      hypercortisolism, making ghrelin an unlikely candidate for causing the changes in
      energy balance or body composition characteristic of Cushing's disease. However,
      the reduced ghrelin secretion could reflect a compensation mechanism in reaction
      to the metabolic consequences of chronic hypercortisolism.

PMID- 15248831
TI  - Effect of oral glucose administration on ghrelin levels in obese children.
AB  - OBJECTIVE: Coexpression of GH secretagogue receptor and ghrelin in the pancreas
      suggests that this peptide is involved in glucose metabolism. Previous reports in
      adult humans have demonstrated that plasma ghrelin levels decrease after oral
      glucose administration. However, no data are available in children. Therefore,
      the aim of this study was to analyze the response of plasma ghrelin levels in
      obese children after oral glucose administration. SUBJECTS AND METHODS: Twenty
      eight obese children ranging from Tanner I to Tanner V were studied. All subjects
      were given 0.75 g/kg (maximum 75 g) glucose solution after overnight fasting.
      Ghrelin, insulin, glucose and IGF-binding-protein-1 were determined at 0, 30, 60
      and 120 min of the oral glucose tolerance test (OGTT). RESULTS: Basal plasma
      ghrelin levels were significantly lower than in the respective control groups.
      These levels decreased significantly during OGTT in obese children, reaching a
      nadir of 28+/-9% at 60 min in parallel with the maximum increase in glucose
      levels and previous to maximum insulin levels. CONCLUSION: The rapid fall in
      plasma ghrelin concentration in obese children after glucose load suggests a
      mechanism for the control of appetite after food intake.

PMID- 15248832
TI  - Insulin determination by specific and unspecific immunoassays in patients with
      insulinoma evaluated by the arterial stimulation and venous sampling test.
AB  - OBJECTIVE: The aim of this study was to compare insulin concentrations measured
      by a traditional radioimmunoassay (RIA) and a more specific enzyme-linked
      immunosorbent assay (ELISA) in blood samples obtained during the arterial
      stimulation and venous sampling (ASVS) test in patients with insulinoma. DESIGN:
      Prospective case series. METHODS: In 14 patients with an insulinoma undergoing an
      ASVS test, blood samples were obtained from the hepatic vein at baseline and 60 s
      after calcium injection into an artery supplying the tumour and a control artery
      (supplying pancreatic tissue without tumour). A selective arterial calcium
      stimulation was performed in five additional patients without evidence for an
      insulinoma. We measured insulin by a traditional RIA and a specific immunoassay.
      RESULTS: In patients with insulinoma, insulin concentrations increased between
      2.3- and 24.2-fold (median 8.2-fold) when measured by RIA and between 7.3- and
      59.4-fold (median 16) when measured by ELISA following calcium injection into the
      artery supplying the tumour. Following calcium injection into the control artery,
      insulin concentrations were 0.6 to 1.3 times (median 1.0) the baseline values by
      RIA and 0.5 to 2.5 times (median 1.1) the baseline values by ELISA. In patients
      without insulinoma, insulin concentrations increased following calcium
      stimulation between 0.7- and 2.1-fold (median 1.3-fold) when measured by RIA and
      between 0.6- and 4.7-fold (median 1.3-fold) when measured by ELISA. CONCLUSIONS:
      When insulin is measured by specific immunoassays, a higher cut-off (i.e. five-
      to sixfold increase) rather than the traditional criterion of a twofold increase
      should be used to localise an insulinoma during the ASVS test. The increase in
      insulin concentrations following calcium stimulation is significantly higher when
      insulin is measured by a specific assay compared with results obtained with
      traditional RIAs.

PMID- 15248833
TI  - Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric
      data in children and adolescents.
AB  - BACKGROUND: Previous investigations on the ghrelin gene reported three common
      polymorphisms (Arg51Gln, Leu72Met, and Gln90Leu), but their role in overweight
      and obese individuals remains to be clarified. OBJECTIVE: To ascertain whether
      these genetic variants could influence ghrelin secretion and play a part in
      predisposing to earlier onset of obesity or in modulating the overweight
      phenotype in childhood. DESIGN AND METHODS: Mutational analysis of the entire
      ghrelin gene and total and acylated plasma determinations were performed in 81
      obese or overweight children and adolescents (46 were obese and 35 overweight:
      Ob/Ow). We also recruited 168 normal-weight healthy controls (72 young adults and
      96 children) for mutational or plasma ghrelin analysis. RESULTS: Median total and
      acylated plasma ghrelin concentrations were significantly lower in Ob/Ow
      individuals than in controls (175 pg/ml compared with 345 pg/ml, P<0.0001, and 95
      pg/ml compared with 114 pg/ml, P<0.0001, respectively). The ghrelin gene variants
      showed similar allele frequencies in the Ob/Ow individuals and in controls; in
      the former, they were not associated with any change in total and acylated
      circulating ghrelin concentrations or anthropometric data. The Leu72Met status
      was associated with a positive family history for obesity (75% for Leu72Met
      compared with 39% for Leu72Leu, P=0.03) and with a greater percentage of newborns
      born 'large for gestational age' (33% for Leu72Met compared with 5% for Leu72Leu,
      P=0.03), but in the control group it was related to a lower mean body mass index
      z-score (-0.03 for Leu72Met and -0.47 for Leu72Leu, P=0.04). CONCLUSION: Our
      present findings do not support the hypothesis that the ghrelin gene
      polymorphisms have a relevant impact in the secretion of total and acylated
      ghrelin.

PMID- 15248834
TI  - Adiponectin may play a part in the pathogenesis of diabetic retinopathy.
AB  - OBJECTIVES: To measure plasma adiponectin concentrations in patients with type 2
      diabetes and to investigate any association with the severity of diabetic
      retinopathy, because adiponectin seems to be an important modulator for metabolic
      and vascular diseases. METHODS: Seventy-four patients (mean age 46.8+/-5.1 years;
      body mass index (BMI), 26.8+/-2.10 kg/m(2)) and 54 healthy volunteers (mean age
      46.8+/-5.4 years; BMI 26.47+/-2.33 kg/m(2)) were included. RESULTS: Adiponectin
      concentrations in the patients were significantly lower than those in controls
      (4.71+/-2.11 microg/ml for patients, n=74; 15.95+/-3.72 microg/ml for controls,
      n=54; P<0.001). In the patients group there was a significant negative
      correlation between adiponectin and homeostasis model assessment index (r=-0.318,
      P=0.006 respectively). Plasma adiponectin concentrations in patients with
      proliferative diabetic retinopathy (n=20; 3.16+/-1.83 microg/ml) or non
      proliferative diabetic retinopathy (n=24; 3.97+/-1.47 microg/ml, P=0.014) were
      significantly lower than those in patients without diabetic retinopathy (n=30;
      6.30+/-1.57 microg/ml, P=0.001). When the presence of diabetes was defined as the
      final variable in the conditional logistic regression model with the adiponectin
      concentration as the continuous variable, adiponectin was significantly involved
      in the model. CONCLUSION: The results show that adiponectin concentrations are
      lower in patients with type 2 diabetes and that the concentrations are associated
      with the severity of diabetic retinopathy. Our findings suggest that adiponectin
      may take part in the pathogenesis of diabetic retinopathy.

PMID- 15248835
TI  - Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on
      human endometrial and ovarian cancer cells are not mediated through the GnRH type
      I receptor.
AB  - BACKGROUND: The majority of human endometrial and ovarian cancer cell lines
      express receptors for GnRH. Their proliferation is time- and dose-dependently
      reduced by GnRH-I and its superagonistic analogues. Recently, we have
      demonstrated that, in human endometrial and ovarian cancer cell lines except for
      the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has
      antiproliferative effects comparable to those of GnRH-I agonists, indicating that
      the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH
      system in cancer cells. We were also able to show that the proliferation of human
      endometrial and ovarian cancer cells was dose- and time-dependently reduced by
      GnRH-II to a greater extent than by GnRH-I agonists. OBJECTIVE: In this study we
      have assessed whether or not the antiproliferative effects of the GnRH-I
      antagonist cetrorelix in endometrial and ovarian cancer cells are mediated
      through the GnRH-I receptor. METHODS: We analysed the antiproliferative effects
      of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II
      in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I
      receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I
      receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell
      lines. RESULTS: We found that, after knockout of the GnRH-I receptor, the
      antiproliferative effects of the GnRH-I agonist triptorelin were abrogated,
      whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted.
      CONCLUSIONS: These data suggest that, in endometrial and ovarian cancer cells,
      the antiproliferative effects of cetrorelix and of GnRH-II are not mediated
      through the GnRH-I receptor.

PMID- 15248836
TI  - Identification of an alternative splicing transcript for the resistin gene and
      distribution of its mRNA in human tissue.
AB  - OBJECTIVE: Adipocytes secrete a number of molecules such as tumor necrosis factor
      alpha, leptin and free fatty acids that can influence the ability of the body to
      metabolize glucose. Recently, a novel 12.5 kDa cysteine-rich protein, termed
      resistin, was shown to be secreted by adipocytes. Resistin expression was
      markedly induced during the conversion of 3T3-L1 cells to mature adipocytes.
      Expression of resistin has been studied in human, mouse and rat; however,
      sequence information about an alternative splicing variant (ASV) of resistin mRNA
      has not been reported. In the present study, we investigated the occurrence of a
      novel ASV of the resistin gene in human normal tissues. DESIGN AND METHODS: We
      identified a novel ASV of resistin mRNA in human lung tissue by RT-PCR analysis
      in human lung tissue. We then investigated a novel ASV of resistin mRNA by real
      time PCR analysis in 26 different types of normal human tissues. RESULTS AND
      CONCLUSIONS: We identified a novel deletion variant of the resistin transcript in
      the normal human tissues. The deleted transcript of resistin was characterized by
      an in-frame deletion of 78 bp, corresponding to the complete loss of exon 2
      (resistin delta2 ASV). Thus, resistin delta2 ASV causes protein truncation. Our
      results provide the basis for more detailed studies on the regulation of resistin
      activity, and should assist in the development of clinical trials with resistin
      for the central regulation of adipogenesis and adipocyte metabolism.

PMID- 15248837
TI  - A questionnaire survey concerning the most favourable treatment for Graves'
      disease in children and adolescents.
AB  - Graves' disease (GD) is the most common cause of juvenile thyrotoxicosis in
      children and adolescents (1, 2). Three treatment modalities are now available for
      the treatment of Graves' thyrotoxicosis in childhood: antithyroid drugs (ATD),
      surgery and radioactive iodine (RAI). However, none of these treatments has been
      shown to be ideal or clearly superior to the others. Physicians in different
      countries have different approaches concerning the optimal treatment of juvenile
      GD. In a European questionnaire study (3), which was conducted by the European
      Thyroid Association in 1993 and in which 99 individuals or groups from 22
      countries participated, it was found that 22 out of 99 physicians from nine
      countries would consider RAI treatment as the treatment of choice for children
      with recurrent thyrotoxicosis after surgery, or with recurrent thyrotoxicosis 2
      years after ATD. However, RAI is preferred by only a small percentage of
      physicians for this group of patients in Europe. Hardly any of the respondents
      chose RAI for the patients with a toxic adenoma or a multinodular toxic goiter
      (3). On the other hand, in view of the difficulties with medical therapy in
      children and adolescents, including poor compliance, a high rate of relapse, drug
      toxicity and continued thyroid enlargement, some eminent American physicians
      emphasize the safety, simplicity and economic advantages of (131)I ablation which
      should be considered more commonly in children (4, 5). We had the opportunity to
      conduct a similar study during a pediatric thyroidology symposium, which was
      organized by Professors Buyugkebiz and Laron in Izmir (Smyrna) Turkey from 30
      October to 1 November 2003. During the congress a questionnaire with the
      following four questions was circulated among the 120 participants from eight
      countries who were mainly paediatric endocrinologists. Most of them were from
      Turkey and the rest, except for one who came from the USA, were Europeans. Sixty
      one out of the 120 physicians responded.

PMID- 15248838
TI  - Characterization of a transport and detoxification pathway for the antitumour
      drug bleomycin in Saccharomyces cerevisiae.
AB  - BLM (bleomycin) is effective in combination therapy against various cancers
      including testicular cancer. However, several other cancers such as colon cancer
      are refractory to BLM treatment. The exact mechanism for this differential
      response of cancer cells to the drug is not known. In the present study, we
      created fluorescently labelled BLM-A5, which retained nearly full genotoxic
      potential, and used this molecule to conduct the first study to understand the
      transport pathway of the drug in Saccharomyces cerevisiae. Uptake studies
      revealed that fluoro-BLM-A5 is transported into the cell in a concentration
      dependent manner. Transport of a non-saturating concentration of fluoro-BLM-A5
      was modest for the first 90 min, but thereafter it was sharply induced until 300
      min. The inducible transport was completely abolished by the addition of
      cycloheximide, suggesting that BLM-A5 uptake into the cell is dependent on new
      protein synthesis. Interestingly, transport of fluoro-BLM-A5 was blocked if the
      cells were preincubated with increasing concentrations of spermine. Moreover, a
      mutant lacking the Ptk2 kinase, necessary for positively regulating polyamine
      transport, was defective in fluoro-BLM-A5 uptake and exhibited extreme resistance
      to the drug. A simple interpretation of these results is that BLM-A5 may enter
      the cell through the polyamine transport system. We showed further that after the
      uptake, fluoro-BLM-A5 accumulated into the vacuole of the parent, but localized
      to the cytoplasm of mutants disrupted for the END3 gene required for an early
      step of the endocytotic pathway. In general, mutants with a defect in the
      endocytic pathway to the vacuole were hypersensitive to BLM-A5. We suggest that
      BLM-A5 is transported across the yeast plasma membrane and sequestered into the
      vacuole for detoxification.

PMID- 15248840
TI  - Nerve growth factor and the vanilloid receptor: partners in crime?

PMID- 15248841
TI  - Pros and cons of microarray technology in allergy research.

PMID- 15248842
TI  - The allergy epidemic extends beyond the past few decades.
AB  - BACKGROUND: Increased prevalence of allergic diseases in western societies has
      been described as an epidemic. The precise turning point for the epidemic and the
      antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the
      prevalence of atopic disease has changed in terms of detectable sensitization to
      aeroallergens and dietary allergens in a cross-sectional comparison of subjects
      from birth cohorts more than 60 years apart. METHODS: We studied four groups of
      100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in
      1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE
      concentrations against aeroallergens and dietary allergens were determined. A
      questionnaire elicited information on symptoms, allergic diseases and medication.
      RESULTS: The proportion of subjects with detectable IgE antibodies against
      aeroallergens increased consistently from the oldest to the youngest birth
      cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in
      sensitization to dietary allergens. The proportion of those with diagnosed asthma
      differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest
      prevalence of asthma and sensitization to dietary allergens was detected in those
      born in 1943-46, i.e. during or immediately after World War II. CONCLUSION:
      Prevalence of sensitization to airborne allergens, unlike that to dietary
      allergens, has increased over a long period of time. Our results support the
      concept of the immune function being programmed by external factors early in
      life. They also call for caution when interpretations of the pace and possible
      causes of the allergy epidemic are made on the basis of short-term studies.

PMID- 15248843
TI  - Antibiotic use in the first year of life and asthma in early childhood.
AB  - BACKGROUND: An association between antibiotic use in early life and asthma in
      childhood has been reported in five retrospective studies and one longitudinal
      study. OBJECTIVE: To examine the relation between the use of oral antibiotics in
      the first year of life and asthma in early childhood. METHODS: Longitudinal
      follow-up of 4408 children enrolled in a health maintenance organization (HMO)
      from birth to the age of 5 years. RESULTS: After adjusting for sex and illnesses
      of the lower respiratory tract (LRIs), we found a significant association between
      antibiotic use in the first year of life and asthma between the ages of 1 and 2
      years (odds ratio (OR) for 1-2 vs. no courses of antibiotics=1.9, 95% confidence
      interval (CI)=1.3-2.7; OR for 3-4 vs. no courses of antibiotics=1.6, 95% CI=1.1
      2.4; OR for at least 5 vs. no courses of antibiotics=2.1, 95% CI=1.5-3.2). After
      adjustment for sex and LRIs in the first year of life, there was no significant
      association between antibiotic use in the first year of life and asthma that was
      initially diagnosed between the ages of 2 and 5 years and that persisted up to
      the age of 5 years (OR for 1-2 vs. no courses of antibiotics=1.1, 95% CI=0.8-1.4;
      OR for 3-4 vs. no courses of antibiotics=1.3, 95% CI=0.9-1.8; OR for at least 5
      vs. no courses of antibiotics=1.0, 95% CI=0.7-1.4). Conclusions Our findings do
      not support the hypothesis that antibiotic use in early life is associated with
      the subsequent development of asthma in childhood but rather suggest that
      frequent antibiotic use in early life is more common among asthmatic children.

PMID- 15248844
TI  - Increased prevalence of asthma and allied diseases among active adolescent
      tobacco smokers after controlling for passive smoking exposure. A cause for
      concern?
AB  - BACKGROUND: Whereas effects on allergic and respiratory health have been
      established for passive tobacco smoking, contradictory results still exist for
      active tobacco smoking. OBJECTIVE: Whether adolescents with asthma and allied
      diseases have higher rates of active smoking compared with adolescents without
      asthma was assessed after controlling for environmental tobacco smoking exposure.
      METHODS: A population-based sample of 14,578 adolescents was enrolled in an
      epidemiological survey on allergies in France. RESULTS: After controlling for
      age, sex, geographic region, familial allergy and passive smoking, current (in
      the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%),
      current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema
      (9.3%) but not lifetime eczema (22.5%) were all significantly related to active
      smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and
      lifetime asthma or current eczema was seen in smokers exposed to passive smoking
      compared with smokers not exposed to it using a polychotomous logistic regression
      model, in which the different modalities of exposure to active and passive
      smoking constituted the response variable. Passive smoking was significantly
      associated only with current diseases. Active smoking was also highly related to
      both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe
      rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents
      suffering from the co-morbidity of lifetime asthma and hayfever (3.6%) was also
      seen in active smokers compared with passive and non-smokers (5.5% vs. 3.6% and
      3.1%, respectively; P=0.001). CONCLUSIONS: Being asthmatic or allergic does not
      seem to act as a deterrent towards starting active smoking or continuing to smoke
      in adolescence. Results suggest the need for considering individual allergic
      status in programming health educational activities aimed at reducing smoking
      among adolescents.

PMID- 15248845
TI  - Compliance of asthmatic families with a primary prevention programme of asthma
      and effectiveness of measures to reduce inhalant allergens--a randomized trial.
AB  - BACKGROUND: Compliance to and the effect of pre- and post-natal exposure
      reduction measures to prevent asthma in high-risk children from asthmatic
      families were studied. METHOD: Families were randomized to a special care group
      (n=222) and a control group (n=221). Educational advice on measures to reduce
      their newborn's exposure to allergens and smoke was provided to the special care
      group during three visits (two pre-natal and one post-natal). The control group
      (n=221) received usual care. RESULT: After the intervention, the special care
      group differed significantly (P<0.01) from the usual care group in: use of anti
      mite encasings (parental: 88% vs. 14%; baby: 98% vs. 10%); keeping pets outside
      (51% vs. 19%); combined breast- and hypoallergenic formula feeding (55% vs. 22%);
      first solids postponement until after the sixth month (71% vs. 28%); maternal
      post-natal smoking (52% vs. 28%). Little or no compliance was found for other
      sanitary measures (cleaning habits, providing a smooth floor covering,
      ventilation/airing, pet removal), exclusive breastfeeding, pre-natal smoking and
      partner smoking. In spite of pre-existent low allergen levels in both groups,
      there was a significant reduction of mite, cat, and dog allergens on the
      mattresses and mite and cat allergens in the living room in the special care
      group and were significantly lower compared with the usual care group after 1
      year. CONCLUSION: High compliance was found for the use of anti-mite encasings;
      substantial compliance for using hypoallergenic formula, solid food postponement,
      keeping pets outside and reported post-natal maternal smoking. There was no
      compliance for sanitary measures and the reduction of maternal pre-natal passive
      smoking. Mite and pet allergens on mattresses were strongly reduced by anti-mite
      encasings.

PMID- 15248846
TI  - Japanese cedar pollen-specific interleukin-4 production develops immediately
      after the first exposure to pollens in infants with atopic dermatitis.
AB  - BACKGROUND: Japanese cedar pollens (JCPs) spread over most areas of Japan from
      February to April and cause pollenosis. While IgE synthesis against JCPs starts
      after age 1, it remains to be clarified when JCP-specific T helper cells acquire
      the ability to produce IL-4, a cytokine that induces IgE synthesis. OBJECTIVE:
      This study aimed to clarify when the sensitization of T cells to JCPs develops.
      METHODS: Peripheral blood mononuclear cells from 153 children with atopic
      dermatitis (AD) aged 0-15 years were stimulated with a standardized JCP allergen.
      As parameters of T cell responsiveness, lymphocyte proliferation and the
      production of IL-4 and IFN-gamma were measured. RESULTS: T cell responses against
      JCPs were negative before March in infants with AD who had never been exposed to
      JCPs or who were exposed for less than a month (nine, seven and nine subjects for
      lymphocyte proliferation, cytokine production and IgE synthesis, respectively).
      Lymphocyte proliferation distinctly increased in 67.6% (23/34) of infants with AD
      examined between March and June. JCP-specific IL-4 production was observed in
      56.0% (14/25) of infants with AD examined between March and June.
      Correspondingly, a slight increase in the level of serum JCP-specific IgE
      antibody was seen in 17.2% (five of 29) of infants with AD examined between April
      and June. CONCLUSION: These results demonstrate that the sensitization of T cells
      to JCPs is effectively completed within a few months after the first exposure to
      JCPs.

PMID- 15248848
TI  - beta2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function
      and asthma in infants and children.
AB  - BACKGROUND: We have previously reported a relationship between increased airway
      responsiveness (AR) in infancy and reduced childhood lung function. OBJECTIVE:
      The current study aimed to determine whether the Arg16Gly polymorphism of the
      beta2 adrenoceptor (beta2AR) gene was important to this relationship. METHODS: A
      cohort that initially numbered 253 individuals underwent assessments of AR and
      lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the
      beta(2)AR was performed. RESULTS: At 1 month of age, the genotype homozygous
      Arg16 (n=24) was associated with a mean increase in log dose-response slope (AR)
      of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype
      homozygous Gly16 (n=58), P=0.01. At 11 years of age, the genotype homozygous
      Arg16 (n=35) was associated with a mean reduction in the percentage of forced
      expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype
      homozygous Gly16 (n=65), P=0.03. There was no association between the Arg16Gly
      polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with
      the genotype homozygous Gly16 were admitted to hospital with asthma compared with
      five out of 111 individuals with the remaining genotypes (P<0.05). CONCLUSION:
      The Arg16Gly polymorphism may be important to the association between increased
      AR in infancy and reduced lung function in childhood and may also be a
      determinant of asthma severity in children but not asthma per se.

PMID- 15248847
TI  - Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of
      association with asthma but association with serum total immunoglobulin E levels
      in adult atopic dermatitis.
AB  - BACKGROUND: Mast cell chymase has the potential to be an important mediator of
      inflammation and remodelling in the asthmatic lung. Previous studies have
      examined association between promoter polymorphism of the chymase gene (CMA1) and
      allergic phenotypes but the significance of this polymorphism is unclear. We have
      examined association of a CMA1 variant in relation to asthma in a large UK
      Caucasian family cohort. METHODS: A polymorphism of the CMA1 gene promoter (
      1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults
      recruited from the UK PCR-RFLP based genotyping. Association with asthma
      diagnosis, atopy, specific and total IgE, and atopy and asthma severity was
      examined. RESULTS: Case-control studies did not reveal a significant difference
      in allele frequency between asthmatics and controls. A significant association
      was found between CMA1 genotypes and total IgE levels in subjects with self
      reported eczema that remained significant after correction for multiple testing
      (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032).
      CONCLUSION: These data suggest that CMA1 promoter polymorphism does not
      contribute to asthma susceptibility or severity but may be involved in regulating
      IgE levels in patients with eczema.

PMID- 15248849
TI  - Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus
      among Finnish asthma families.
AB  - OBJECTIVE: T-box expressed in T cells (T-bet) is a transcription factor
      regulating the commitment of T helper (Th) cells by driving the cells into the
      Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma
      or autoimmune diseases. Recent studies have suggested that T-bet might be a
      candidate gene for asthma. This led us to screen 23 Finnish individuals for
      single-nucleotide polymorphisms (SNPs) in the T-bet locus and study the
      association between the SNPs and high serum IgE level and asthma. METHODS: We
      screened all six exons, adjacent intronic areas and 2 kb of the 5'-flanking
      region from 23 individuals utilizing WAVE trade mark technology. To explore
      whether T-bet is associated in serum IgE regulation or asthma we genotyped the
      SNPs in a Finnish asthmatic founder population. The association analyses were
      made using haplotype pattern mining. RESULTS: Fifteen novel SNPs were found in
      the T-bet gene. Within the Finnish asthmatic founder population, there was no
      association between T-bet SNPs and high serum IgE level or asthma. CONCLUSIONS:
      The genetic variability in the T-bet gene does not play a role in the
      pathogenesis of human asthma. Our results provide a novel panel of SNPs in T-bet
      and will help determine whether the SNPs have a functional role in other T cell
      mediated diseases.

PMID- 15248850
TI  - Asymptomatic atopy is associated with increased indoleamine 2,3-dioxygenase
      activity and interleukin-10 production during seasonal allergen exposure.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan (TRP)-catabolizing
      enzyme with regulatory effects on T cells. T cell inhibition is achieved through
      both TRP depletion and TRP metabolite accumulation in specific local tissue
      microenvironments. The expression of IDO activity by different types of antigen
      presenting cells (APCs) has been shown to play a role in many instances of
      immunoregulation and tolerance induction. Induction of IDO after the engagement
      of the high-affinity receptor for IgE, FcepsilonRI, on atopic monocytes has been
      suggested to regulate T cell responses in atopic disorders. Interleukin-10 (IL
      10), a cytokine known for its down-regulatory functions in the immune system, has
      recently been associated with the stable expression of IDO in mature tolerogenic
      dendritic cells. OBJECTIVE: This study was devised to understand the role of
      systemic IDO and IL-10 in the prevention of clinical apparent allergy. METHODS:
      The concentration of TRP and the break-down product kynurenine were measured by
      high-performance liquid chromatography in- and off-season in sera from patients
      with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic
      patients sensitized to specific aeroallergens (n=12). Non-atopic (NA) individuals
      (n=12) served as control. The concentration of plasma IL-10 was determined in
      parallel from these donors by ELISA in- and off-season. RESULTS: In clinically
      unresponsive but aeroallergen-sensitized atopic individuals significantly higher
      systemic activity of IDO and increased plasma IL-10 levels were found during
      allergen exposure but not off-season compared to symptomatic atopic individuals
      with allergic rhinitis and NA individuals. CONCLUSION: Enhanced systemic IDO
      activity as well as increased systemic levels of IL-10 may contribute to the
      containment of allergic T cell responses and could be involved in the maintenance
      of a state of clinical unresponsiveness.

PMID- 15248851
TI  - Interleukin-5 receptors on human lung eosinophils after segmental allergen
      challenge.
AB  - BACKGROUND: IL-5 is a specific cytokine for eosinophil accumulation, activation
      and prolongation of survival and can be recovered in elevated concentrations from
      the bronchoalveolar compartment in atopic asthma following allergen challenge.
      OBJECTIVE: The action of IL-5 is mediated via the specific IL-5 receptor-alpha
      (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated
      by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its
      kinetics following allergen provocation are incompletely understood. METHODS: We
      investigated IL-5R regulation in vivo following segmental allergen provocation
      (SAP) with an individually standardized dose of allergen in 12 patients with
      atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min
      and 42 h (eight patients) after allergen challenge. In addition to differential
      cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in
      bronchoalveolar lavage (BAL) fluid were determined by ELISA. RESULTS: IL-5Ralpha
      expression decreased significantly on peripheral blood and on BAL eosinophils 18
      and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in
      BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there
      were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure.
      CONCLUSIONS: Although there was no correlation between IL-5 concentrations and IL
      5Ralpha expression on eosinophils in BAL, our data support previous in vitro and
      in vivo findings of a negative feedback mechanism between IL-5 concentrations and
      IL-5Ralpha expression on eosinophils.

PMID- 15248852
TI  - Allergen activates peripheral blood eosinophil nuclear factor-kappaB to generate
      granulocyte macrophage-colony stimulating factor, tumour necrosis factor-alpha
      and interleukin-8.
AB  - BACKGROUND: Allergic inflammation is characterized by the influx and activation
      of eosinophils. Cytokines generated by both resident and infiltrating cells are
      responsible for the initiation and maintenance of this pathogenesis. This study
      focuses on allergen-induced activation of eosinophil NF-kappaB and generation of
      granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8.
      METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient
      sedimentation and negative magnetic affinity chromatography. NF-kappaB activation
      by 10 microg/mL house dust mite (HDM) extract was demonstrated
      immunocytochemically using a monoclonal antibody against the active form of NF
      kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot.
      Cytokine production was assessed both by immuno-staining of eosinophils and by
      assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral
      blood eosinophils from atopic, but not non-atopic, donors induced activation of
      NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha.
      The activation of authentic NF-kappaB was confirmed in gel shift assays.
      Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB.
      Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to
      the nucleus. Following activation, cytokine immunoreactivity was seen in a
      fraction of the eosinophils and cytokines were released into the supernatant. The
      NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm),
      pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the
      generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF
      kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to
      the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a
      role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop
      augmenting the survival of eosinophils in vivo.

PMID- 15248853
TI  - Effect of anti-immunoglobulin E on nasal inflammation in patients with seasonal
      allergic rhinoconjunctivitis.
AB  - BACKGROUND: Binding of allergens to IgE on mast cells and basophils causes
      release of inflammatory mediators in nasal secretions. OBJECTIVE: The combined
      effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal
      anti-IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase,
      IL-6, and IL-8 in nasal secretion was evaluated. METHODS: Two hundred and twenty
      five children (aged 6-17 years) with a history of seasonal allergic
      rhinoconjunctivitis induced by birch and grass pollen were randomized into four
      groups: either birch- or grass-pollen SIT in combination with either anti-IgE or
      placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1),
      during birch- (V2) and grass (V3)-pollen season and after the pollen season (V4)
      were collected from 53 patients. RESULTS: A significant reduction in tryptase
      only was seen in the anti-IgE-treated group at V2 (P<0.05) and V4 (P<0.05)
      compared with the placebo group. During the pollen season, patients with placebo
      showed an increase of ECP compared with baseline (V2: +30.3 microg/L; V3: +134.2
      microg/L, P< 0.005; V4: +79.0 microg/L, P< 0.05), and stable levels of tryptase,
      IL-6 and IL-8. Treatment with anti-IgE resulted in stable ECP values and a
      significant decrease of tryptase compared with V1 (baseline): V2: -80.0 microg/L
      (P< 0.05); V3: -56.3 microg/L, which persisted after the pollen season with V4: 
      71.6 microg/L (P< 0.05). After the pollen season, a decrease of IL-6 was observed
      in both groups (V4 placebo group: -37.5 ng/L; V4 anti-IgE group: -42.9 ng/L, P<
      0.01). CONCLUSION: The combination of SIT and anti-IgE is associated with
      prevention of nasal ECP increase and decreased tryptase levels in nasal
      secretions.

PMID- 15248854
TI  - In vitro diagnosis of chronic nasal inflammation.
AB  - BACKGROUND: Differential diagnosis of chronic nasal inflammation is insufficient
      when based solely on clinical examination and radiography of paranasal sinuses.
      Patients complain about more or less similar symptoms. Activation of mast cells
      and eosinophils is pivotal in nasal inflammation. OBJECTIVE: To compare tryptase
      and eosinophilic cationic protein (ECP) in nasal secretions in different forms of
      chronic nasal inflammation and to establish norm values. METHODS: The study
      included 1710 patients presenting with nasal complaints. Nasal secretions were
      gained by the cotton wool method and analysed for tryptase, as a marker of mast
      cell activation, and for ECP, as a marker of tissue eosinophilia and activation.
      Patients were grouped according to their diagnosis: chronic, non-allergic
      rhinosinusitis (sinusitis, n=194), non-allergic nasal polyposis (polyposis,
      n=138), non-allergic rhinitis with eosinophilia syndrome (NARES, n=198), isolated
      perennial allergic rhinitis (AR) (n=126), isolated seasonal AR (n=132), and
      patients allergic to both, seasonal and perennial allergens (n=193). Seven
      hundred and twenty-nine patients with nasal complaints due to a deviated septum
      and without any nasal inflammation served as controls. RESULTS: Nasal tryptase
      was highly significantly (P<0.001) elevated in polyposis, NARES, and in AR. ECP
      was highly significantly (P<0.001) elevated in all groups of patients suffering
      from chronic nasal inflammation. Based on our data and method we established norm
      values (95% confidence interval of mean value) for nasal tryptase in healthy
      adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6
      ng/mL. CONCLUSION: Mast cells and eosinophils are involved in non-allergic and
      allergic forms of chronic nasal inflammation. We established an in vitro assay
      for tryptase and ECP in nasal secretions and defined norm values based on our
      data and method. In vitro measurement of biological markers in nasal secretions
      provides important information for differential diagnosis and therapeutic
      strategies of chronic nasal inflammation.

PMID- 15248855
TI  - Acoustic rhinometry in nasal allergen challenge study: which dimensional measures
      are meaningful?
AB  - BACKGROUND: Acoustic rhinometry (AR) is commonly used as a quantitative
      assessment of nasal response to nasal allergen challenge (NAC). However, sources
      of error and physical limitations of various AR area-distance measurements have
      not been adequately evaluated. OBJECTIVE: To investigate the clinical value of AR
      measurements, and the relationship between subjective sensation and objective AR
      measurements in the NAC study. METHODS: Nasal challenge using increasing
      concentrations of crude Blomia tropicalis (Bt) extracts (0.6, 6, and 60
      microg/mL) was performed in 15 adult patients (eight males and seven females)
      with ongoing persistent allergic rhinitis. Subjective symptom scores of nasal
      obstruction were recorded together with the objective AR measurements of the
      minimum cross-sectional area (MCA), distance to MCA and cross-sectional area
      (CSA) at 3.3, 4.0 and 6.4 cm from the nostril, during the 7 h after the last
      challenge. RESULTS: The dose-response increase in nasal obstruction score was
      significantly (P<0.001 for all) associated with decreases in mean MCA (r=0.75),
      mean CSA3.3 (r=0.54), mean CSA4.0 (r=0.53) and mean CSA6.4 (r=0.20). The mean MCA
      (+/-SD) for each subjective symptom score 0, 1, 2 and 3 was found to be 0.73 (+/
      0.22) cm2, 0.63 (+/-0.29) cm2, 0.33 (+/-0.17) cm2 and 0.21 (+/-0.14) cm2,
      respectively. When the MCA (left and right separately) reached an area <0.2 cm2,
      measurements of CSA3.3 and CSA4.0 were significantly reduced by 60-70%.
      CONCLUSION: This study demonstrates that AR is a useful and objective
      investigational tool, which correlates well with the sensation of nasal
      obstruction. MCA, CSA3.3 and CSA4.0 are more reliable measurements than CSA6.4
      due to physical limitations. It is important to note that when the MCA is smaller
      than 0.2 cm2, a common condition in the early-phase reaction, area-distance
      measurements beyond this point can be misinterpreted and should be considered
      with caution.

PMID- 15248856
TI  - Nasal conditioning in perennial allergic rhinitis after nasal allergen challenge.
AB  - BACKGROUND: Antigen challenge in seasonal allergic rhinitis is considered to be
      associated with an increased ability of the nose to condition inspired air. In
      contrast, little is known about air conditioning after antigen challenge in
      perennial allergic rhinitis (PAR). OBJECTIVE: The aims of this study were to
      investigate whether antigen challenge in PAR changes nasal air conditioning and
      to assess the relationship between nasal conditioning and nasal patency and
      geometry. METHODS: Nineteen subjects with PAR were enrolled into this study.
      Measurement of nasal conditioning, active anterior rhinomanometry (AAR), acoustic
      rhinometry (AR), and clinical symptom evaluation were performed before and after
      nasal allergen challenge with allergen extracts from house dust mites. RESULTS:
      Ten and 20 min after nasal allergen challenge, the total water content of the air
      measured in the nasopharynx and the water gradient across the nose were
      significantly higher in the nasal cavity in which the allergen extract was
      sprayed. The temperature on both sides of the nose increased non-significantly
      after nasal allergen challenge. No correlation to data obtained by AAR, AR, and
      clinical symptom evaluation after nasal allergen challenge was found. CONCLUSION:
      We suggest that an increase in mucosal humidity due to the allergic provocation
      might be responsible for the increase in nasal conditioning capacity because no
      correlation to changes in nasal perimeter and patency was found.

PMID- 15248857
TI  - Phenotypic alteration of neuropeptide-containing nerve fibres in seasonal
      intermittent allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease affecting
      the respiratory tract. Next to inflammatory changes, the airway innervation plays
      an important modulatory role in the pathogenesis of the disease. OBJECTIVE: To
      examine the participation of different neuropeptides in the human nasal mucosa of
      intermittent (seasonal) AR tissues in the allergic season. METHODS:
      Immunohistochemistry for substance P (SP), calcitonin gene-related peptide
      (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY)
      was related to the characterization of inflammatory cells in tissues of patients
      with seasonal AR (n=18). RESULTS: While there was a significant increase in the
      number of eosinophils present if compared with a control group, no changes
      occurred in mast cell numbers. Immunostaining was abundantly found in different
      nerve fibre populations of both groups. SP expression was significantly increased
      in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also,
      significantly increased numbers of VIP- and NPY-immunoreactive nerve fibres were
      found in biopsies of rhinitis patients in comparison with sections of normal
      human nasal mucosa. In contrast, CGRP expression did not change significantly.
      CONCLUSION: The increase of neuropeptide expression in mucosal nerve fibres
      indicates a major role of the autonomous mucosal innervation in the
      pathophysiology of intermittent (seasonal) AR.

PMID- 15248858
TI  - Assessment of histamine-releasing activity of sera from patients with chronic
      urticaria showing positive autologous skin test on human basophils and mast
      cells.
AB  - BACKGROUND: All previous studies agree that only a proportion of sera from
      patients with chronic urticaria (CU) positive on the autologous serum skin test
      (ASST) are able to induce histamine release in vitro. A non-specific release of
      bradykinins during clotting of blood samples has been suggested; however, ASST
      seems rather specific and some data point to the existence of a mast cell
      specific histamine-releasing factor. OBJECTIVE: To assess whether, and to what
      extent, the use of both human basophils and mast cells increases the sensitivity
      of in vitro histamine release assays (HRAs) in ASST-positive patients with CU.
      METHODS: The histamine-releasing activity of sera from 93 patients with CU
      selected on the basis of strong skin reactivity on ASST was assessed in vitro on
      basophils from 1 (n=86), 2 (n=31), or 3 (n=20) normal donors, and on mast cells
      from 1 (n=3), 2 (n=3), or 3 (n=87) normal donors. RESULTS: Sera from 88/93 (95%)
      patients induced significant histamine release from mast cells or basophils on at
      least one HRA. 76/93 (82%), 45/90 (50%), 22/80 (28%), and 6/12 (50%) sera were
      able to induce significant histamine release from cells of 2/5, 3/5, 4/5 and 5/5
      donors, respectively. CONCLUSION: Sera from nearly all ASST-positive patients
      with CU are able to induce histamine release in vitro. However, the serum from
      each single patient seems to show its maximal activity on autologous mast cells
      in vivo, and functional in vitro tests show much variability and seem less
      sensitive than ASST in the detection of patients with histamine-releasing factors
      in their blood.

PMID- 15248859
TI  - Kiwi fruit is a significant allergen and is associated with differing patterns of
      reactivity in children and adults.
AB  - BACKGROUND: Allergy to kiwi fruit appears increasingly common, but few studies
      have evaluated its clinical characteristics, or evaluated methods of
      investigating the allergy. OBJECTIVE: To characterize the clinical
      characteristics of kiwi fruit allergy and to study the role of double-blind
      placebo-controlled food challenge (DBPCFC), skin tests and specific IgE in the
      diagnosis of this food allergy. METHODS: Two-hundred and seventy-three subjects
      with a history suggestive of allergy to kiwi completed a questionnaire. Forty
      five were investigated by DBPCFC, prick-to-prick skin testing with fresh kiwi
      pulp, and specific IgE measurement. Nineteen subjects were also skin tested using
      a commercially available solution. RESULTS: The most frequently reported symptoms
      were localized to the oral mucosa (65%), but severe symptoms (wheeze, cyanosis or
      collapse) were reported by 18% of subjects. Young children were significantly
      more likely than adults to react on their first known exposure (P<0.001), and to
      report severe symptoms (P=0.008). Twenty-four of 45 subjects (53%) had allergy
      confirmed by DBPCFC. Prick-to-prick skin test with fresh kiwi was positive in 93%
      of subjects who had allergy confirmed by DBPCFC, and also in 55% of subjects with
      a negative food challenge. The commercial extract was significantly less
      sensitive, but with fewer false-positive reactions. CAP sIgE was only positive in
      54% of subjects who had a positive challenge. CONCLUSIONS: Kiwi fruit should be
      considered a significant food allergen, capable of causing severe reactions,
      particularly in young children. DBPCFC confirmed allergy to kiwi fruit in 53% of
      the subjects tested, who had a previous history suggestive of kiwi allergy. Skin
      testing with fresh fruit has good sensitivity (93%), but poor specificity (45%)
      in this population. CAP sIgE and a commercially available skin test solution were
      both much less sensitive (54%; 75%) but had better specificity (90%; 67%).

PMID- 15248860
TI  - Anaphylaxis after hamster bites--identification of a novel allergen.
AB  - BACKGROUND: Hamsters are popular household pets and anaphylaxis after their bites
      have described. However, the putative allergen has not been identified.
      OBJECTIVE: This study was conducted to identify the allergen causing dwarf
      hamster (Phodopus sungoris) bite-induced anaphylaxis. METHODS: Two children with
      hamster bite-induced anaphylaxis were enrolled. They both had negative results to
      skin testing and specific IgE to hamster epithelium. However, they were both
      allergic to Dermatophagoides pteronyssinus (Der p). Identification of the
      putative IgE-binding allergens from the hamster saliva was performed using
      immunoblot analysis. RESULTS: A specific IgE-binding component at 21 kD in the
      hamster saliva was identified. ELISA inhibition tests showed partial inhibition
      with Der p. CONCLUSIONS: The putative allergen from the hamster saliva causing
      dwarf hamster-induced anaphylaxis was identified. Possible cross-reactivity with
      Der p was demonstrated. Further studies will be needed to identify the exact
      nature and function of this allergen.

PMID- 15248861
TI  - Oral administration of desloratadine prior to sensitization prevents allergen
      induced airway inflammation and hyper-reactivity in mice.
AB  - BACKGROUND: Histamine-1-receptor (H1R)-antagonists were shown to influence
      various immunological functions on different cell types and may thus be employed
      for immune-modulating strategies for the prevention of primary immune responses.
      OBJECTIVE: The aim of this study was to investigate the effects of an H1R
      antagonist on allergen-induced sensitization, airway inflammation (AI) and airway
      hyper-reactivity (AHR) in a murine model. METHODS: BALB/c mice were systemically
      sensitized with ovalbumin (OVA) (six times, days 1-14) and challenged with
      aerosolized allergen (days 28-30). One day prior to the first and 2 h prior to
      every following sensitization, mice received either 1 or 0.01 microg of
      desloratadine (DL) or placebo per os. RESULTS: Sensitization with OVA
      significantly increased specific and total IgE and IgG1 serum levels, as well as
      in vitro IL-5 and IL-4 production by spleen and peribronchial lymph node (PBLN)
      cells. Sensitized and challenged mice showed a marked eosinophilic infiltration
      in broncho-alveolar lavage fluids and lung tissues, and developed in vivo AHR to
      inhaled methacholine. Oral treatment with DL prior to OVA sensitization
      significantly decreased production of OVA-specific IgG1, as well as in vitro Th2
      cytokine production by spleen and PBLN cells, compared with OVA-sensitized mice.
      Moreover, eosinophilic inflammation and development of in vivo AHR were
      significantly reduced in DL-treated mice, compared with sensitized controls.
      CONCLUSION: Treatment with H1R-anatagonist prior to and during sensitization
      suppressed allergen-induced Th2 responses, as well as development of eosinophilic
      AI and AHR. This underscores an important immune modulating function of
      histamine, and implies a potential role of H1R-anatagonists in preventive
      strategies against allergic diseases.

PMID- 15248862
TI  - The remodelled tracheal basement membrane zone of infant rhesus monkeys after 6
      months of recovery.
AB  - BACKGROUND: In previous studies, we showed that repeated exposure to (1) house
      dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the
      basement membrane zone (BMZ) and (2) HDMA+ozone (O3) caused depletion of BMZ
      perlecan and atypical development of BMZ collagen (irregular thin areas<2.0
      microm in width). OBJECTIVE: The purpose of this study was to determine if these
      remodelling changes were reversible after 6 months of recovery. METHODS: Rhesus
      monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6
      months. After the exposure protocol was completed FA and O3 groups were allowed
      to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in
      a modified environment. They were re-exposed to HDMA aerosol for 2 h at monthly
      intervals during recovery in order to maintain sensitization for pulmonary
      function testing. To detect structural changes in the BMZ, collagen I and
      perlecan immunoreactivity were measured and compared to data from the previous
      papers. RESULTS: The remodelled HDMA group had a significantly thicker BMZ and
      after 6 months of recovery the width had not regressed. In the remodelled BMZ of
      the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the
      recovery protocol, and the thin, irregular, collagen BMZ had been resolved.
      CONCLUSION: In summary, this study has shown that: (1) The width of the
      remodelled HDMA BMZ did not regress during a recovery protocol that included a
      sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was
      resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was
      reversed by recovery in the absence of O3.

PMID- 15248863
TI  - Nerve growth factor enhances cholinergic innervation and contractile response to
      electric field stimulation in a murine in vitro model of chronic asthma.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease characterized by airway
      hyper-responsiveness. Alterations in the neurogenic control are believed to
      contribute to the pathogenesis. Yet, the long-term interaction between nerves and
      inflammatory mediators, such as the neurotrophin nerve growth factor (NGF), are
      not fully understood much due to the absence of appropriate experimental assays.
      OBJECTIVE: To develop an ex vivo mouse organ culture assay and to investigate the
      effects of NGF on nerve-mediated airway contractions. METHOD: Mouse tracheal
      segments were cultured in periods of up to 16 days. Their contractile responses
      to electric field stimulation (EFS) were investigated. In addition, the effect of
      4 days of NGF treatment was analysed using EFS and immunohistochemistry. RESULTS:
      EFS (0.2-25.6 Hz) induced reproducible and frequency-dependent cholinergic
      contractions of both fresh and cultured tracheal segments. The main part of the
      EFS response was blocked by tetrodotoxin or atropine. After 4 days in culture,
      regional differences appeared, with stronger EFS responses in distal than in
      proximal segments. More nerve fibres were seen in distal segments than in
      proximal segments. Treatment with NGF during 4 days of culture increased the
      innervation of the proximal segments, at the same time as the cholinergic
      contractile responses to EFS were enhanced dose-dependently. CONCLUSION: Culture
      of tracheal segments appears to be a suitable assay for the examination of long
      term effects induced by inflammatory mediators on neurally mediated airway
      contractions. NGF treatment enhanced the cholinergic, nerve-dependent
      contractions and increased the amount of nerve fibres seen in the murine tracheal
      segments, suggesting a role for NGF in the development of airway hyper
      responsiveness.

PMID- 15248864
TI  - Nerve growth factor induces increased airway inflammation via a neuropeptide
      dependent mechanism in a transgenic animal model of allergic airway inflammation.
AB  - BACKGROUND: Nerve growth factor (NGF) exerts an important functional impact on
      the pathogenesis of allergic diseases. Data obtained in animal models of allergic
      bronchial asthma indicate that NGF alters sensory nerve function and promotes
      allergic inflammation, bronchial hyper-reactivity, and airway obstruction.
      OBJECTIVE: To further delineate the effects of NGF on airway inflammation, we
      employed a transgenic (tg) animal model of allergic inflammation and asthma.
      METHODS: NGF-tg mice, which overexpress NGF in Clara cells of the airways, were
      compared with wild-type (wt) littermates regarding their ability to mount IgE
      related airway inflammatory responses. Mice were sensitized intraperitoneally to
      ovalbumin (OVA) and locally challenged via the airways according to established
      protocols. RESULTS: NGF-tg mice displayed enhanced levels of OVA-specific IgE
      antibody titres after repeated OVA aerosol exposure. In the airways, increased
      numbers of eosinophils were detected. These results were confirmed to be NGF
      specific, because similar results were obtained following local application of
      NGF into the airways of wt mice. The effect of NGF was partly mediated via
      neuropeptides, as treatment of OVA-sensitized NGF-tg mice with the dual
      neurokinin (NK) receptor NK-1/NK-2 antagonist partly prevented enhanced airway
      inflammation. CONCLUSION: The present data indicate an important functional role
      of NGF in allergic airway inflammation and point to an involvement of tachykinins
      as mediators of NGF effects.

PMID- 15248865
TI  - Screening for novel ENU-induced rhythm, entrainment and activity mutants.
AB  - Chemical mutagenesis has provided an opportunity to develop and expand the
      repertoire of behavioural mutants for gene function studies. With this in mind,
      we have established a screen in mice for mutations affecting circadian rhythms,
      entrainment to light and other wheel-running parameters. The screen consists of
      an assessment of mouse wheel-running activity in a 12:12 h light/dark cycle for 7
      10 days followed by assessment in constant darkness for up to 20 days. Responses
      to light are assessed using two protocols; a 15 minute light pulse given at
      circadian time 16 on the tenth day in constant darkness and an additional 12 h of
      light upon transition from light/dark conditions to constant darkness. To date,
      approximately 1300 progeny of chemically mutagenised mice have been screened.
      Computer-aided assessment of wheel-running parameters has helped in identifying
      abnormal phenotypes in approximately 5% of all animals screened. Inheritance
      testing of mice with abnormal phenotypes has confirmed the number of robustly
      inherited mutant phenotypes to be 1% of the total screened. Confirmed mutants
      including those affecting free-running period, light-responsiveness and wheel
      running endurance have been identified. Thus far, low-resolution map positions
      have been established for four mutants by completing genome scans in backcross
      progeny. Mutant loci do not correspond with those previously associated with
      wheel-running behaviour. This result confirms that phenotype-driven approaches
      such as this should continue to provide material for mammalian gene function
      studies.

PMID- 15248866
TI  - Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I:
      motor tests.
AB  - One of the characteristic manifestations in several neurodegenarative diseases is
      the loss of voluntary motor control and the development of involuntary movements.
      In order to determine the suitability of six mouse strains as transgenic
      background strains we investigated performance on a variety of tasks designed to
      identify subtle changes in motor control. On both the accelerating and the
      staggered speed rotarod all six mouse strains performed well. However, latency to
      fall from the rod was sensitive to both rotarod speed and repeated exposure to
      the apparatus. Performance of the DBA/2 mouse strain was highly variable across
      the time points used. On the acoustic startle test CBA mice showed the greatest
      degree of reactivity to the acoustic startle stimuli with both the C57 and DBA
      showing the least. Complex strain differences were also identified on measures of
      habituation to the startle stimuli and variations in the prepulse noise level,
      and prepulse/startle delay. Gait analysis using the footprint test did not reveal
      strain differences on measures of base width, overlap or stride length but the
      129S2/Sv strain took significantly longer to traverse the runway than the other
      mouse strains. Finally, the swim tank test detected complex strain differences in
      swim speed, and the number of fore- and hindpaw paddles required to swim the
      length of the tank. These data taken together suggest that choice of background
      strain is a crucial consideration for the repeated behavioural assessment of
      motor deficits in transgenic mouse models of disease.

PMID- 15248867
TI  - MAO-B knockout mice exhibit deficient habituation of locomotor activity but
      normal nicotine intake.
AB  - Low levels of monoamine oxidase-B (MAO-B) activity, such as those observed in
      smokers, are also associated with behavioral traits such as a heightened
      responsiveness to novelty. However, the exact mechanism by which low MAO-B
      activity influences smoking and heightened responsiveness to novelty is still
      poorly understood. We used MAO-B knockout (KO) mice to test the hypothesis that
      MAO-B concomitantly affects locomotor responses in a novel inescapable open field
      and nicotine intake. Male wild-type (WT) and MAO-B KO mice were placed in an
      inescapable open field and their horizontal locomotor activity was measured for
      30 min per day for 5 days. MAO-B KO mice exhibited impaired within-session
      habituation of locomotor activity, as compared to WT mice. Separate groups of
      male WT and MAO-B KO mice were individually housed in their home cages with two
      water bottles. One of the bottles contained tap water and the other contained
      nicotine (0, 3.125, 6.25, 12.5, 25, 50 or 100 micro g/ml). The total amount of
      water and nicotine solution consumed was measured every three days for 16 days.
      MAO-B KO mice and WT mice consumed equal amounts of nicotine and exhibited
      comparable concentration-dependent nicotine preference and aversion over a period
      of 16 days. The data suggest that the absence of MAO-B impairs the ability of
      mice to habituate in the inescapable environment, but does not alter their
      nicotine intake.

PMID- 15248868
TI  - The impact of genetic background on neurodegeneration and behavior in seizured
      mice.
AB  - We used pilocarpine-induced seizures in mice to determine the impact of genetic
      background on the vulnerability of hippocampal neurons and associated changes of
      behavioral performance. The susceptibility of hippocampal neurons to seizure
      induced cell death paralleled the severity of the seizures and depended on
      genetic background. Hippocampal neurons in C57BL/6 mice were most resistant to
      cell death, whereas they were highly vulnerable in FVB/N mice. The degree of
      neuronal degeneration in F1 hybrid mice obtained by crossing the two strains was
      at an intermediate level between the parent strains. Two weeks after the severe
      seizures, performance in a water-maze place navigation task showed a bimodal
      distribution. Seventeen of 19 (90%) F1 mice were completely unable to learn while
      the other two learned reasonably well. Of 28 C57BL/6 mice with similarly severe
      seizures, six were as strongly impaired as their F1 counterparts (22%). The
      remaining 22 performed normally, indicating a much lower probability of C57BL/6
      mice to be affected. Treated mice showed a deficit of open-field exploration
      which was strongly correlated with the impairment in the place navigation task
      and was again more severe in F1 mice. Our results show that the vulnerability of
      hippocampal neurons to pilocarpine-induced seizures, as well as the associated
      behavioral changes, depended on genetic background. Furthermore, they confirm and
      extend our earlier finding that a relatively modest reduction of hippocampal cell
      death can be associated with dramatic changes of behavioral performance and
      emphasize the importance of tightly-controlled genetic backgrounds in biological
      studies.

PMID- 15248869
TI  - The contribution of three strong candidate schizophrenia susceptibility genes in
      demographically distinct populations.
AB  - Here we characterize and compare the contribution of three recently identified
      strong candidate schizophrenia susceptibility genes; G72, neuregulin 1 (NRG1) and
      dystrobrevin-binding protein 1 (DTNBP1) in two independent datasets of patients
      with distinct genetic backgrounds. On the basis of corrected P-values from single
      and multilocus transmission distortion tests our analysis provides no support
      for a contribution of G72, NRG1 or DTNBP1 in the tested samples. When
      transmission of individual haplotypes was considered, a picture more consistent
      with the original studies emerged, where transmission distortions in the same
      direction as the original samples and involving the same core haplotypes were
      observed for G72 and NRG1. Interestingly, whereas the NRG1 gene analysis was
      dominated by the presence of over-transmitted haplotypes, the G72 gene analysis
      was consistently dominated in both datasets by under-transmissions. Negative
      transmissions involved a core haplotype complementary to the originally detected
      over-transmitted haplotype, suggesting the presence of a protective variant
      within the G72 locus.

PMID- 15248870
TI  - A note on the effect of within-strain sample sizes on QTL mapping in recombinant
      inbred strain studies.
AB  - This note explores the effect of within-strain sample sizes on the correlations
      between a phenotype and a molecular-genetic marker in a battery of inbred
      strains. It is shown that the maximum correlation possible between a molecular
      marker and a behavioral or neuronal phenotype equals the additive-genetic
      correlation. How close the strain correlation will approach the additive-genetic
      correlation depends only on heritability and within-strain sample sizes. The
      equations derived can be used to optimize designs of studies attempting to
      localize Quantitative Trait Loci utilizing Recombinant Inbred Strains, provided
      information about the heritability of the character under study is available.

PMID- 15248872
TI  - Early bone formation adjacent to rough and turned endosseous implant surfaces. An
      experimental study in the dog.
AB  - OBJECTIVE: To validate a proposed model (Berglundh et al. 2003) and to evaluate
      the rate and degree of osseointegration at turned (T) and sand blasted and acid
      etched (SLA) implant surfaces during early phases of healing. MATERIAL AND
      METHODS: The devices used for the study of early healing had a geometry that
      corresponded to that of a solid screw implant with either a SLA or a T surface
      configuration. A circumferential trough had been prepared within the thread
      region (intra-osseous portion) that established a geometrically well-defined
      wound chamber. Twenty Labrador dogs received totally 160 experimental devices to
      allow the evaluation of healing between 2 h and 12 weeks. Both ground and
      decalcified sections were prepared from mesial/distal and buccal/lingual device
      sites. Histometric and morphometric analyses of the ground sections and
      morphometric analysis of the tissue components in decalcified sections were
      performed. RESULTS: The ground sections provided an overview of the various
      phases of tissue formation, while the decalcified, thin sections enabled a more
      detailed study of events involved in bone tissue modeling and remodeling for both
      SLA and T surfaces. The initially empty wound chamber became occupied with a
      coagulum and a granulation tissue that was replaced by a provisional matrix. The
      process of bone formation started already during the first week. The newly formed
      bone present at the lateral border of the cut bony bed appeared to be continuous
      with the parent bone, but on the SLA surface woven bone was also found at a
      distance from the parent bone. Parallel-fibered and/or lamellar bone as well as
      bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more
      bone-to-device contact, more initial woven bone and earlier lamellar bone
      formation was found than in the T chambers. CONCLUSION: Osseointegration
      represents a dynamic process both during its establishment and its maintenance.
      While healing showed similar characteristics with resorptive and appositional
      events for both SLA and T surfaces, the rate and degree of osseointegration were
      superior for the SLA compared with the T chambers.

PMID- 15248873
TI  - Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated
      implants.
AB  - AIM: This study evaluated the impact of the IL-1 genotype and smoking status on
      the prognosis and development of complications of osseointegrated implants.
      MATERIAL AND METHODS: The clinical charts of 180 consecutively admitted patients
      were analyzed with respect to the occurrence of biological complications in
      conjunction with oral implants. Biologic complications were defined as clinical
      conditions with suppuration from the peri-implant sulcus, development of a
      fistula or peri-implantitis with radiologic bone loss. All patients had received
      one or more ITI dental implants, which had been in function for at least 8
      (range: 8-15) years. This patient population had received 292 implants. From
      these, 51 implants in 34 patients showed late (infectious) biologic
      complications, and 241 implants had survived without any biologic complications
      at all. RESULTS: Of the 180 patients, 53 were smokers, who were subdivided in a
      series of classes according to their intensity of smoking and 127 were never
      smokers. Sixty-four of 180 (36%) patients tested positive for the IL-1 genotype
      polymorphism. This prevalence corresponds to previous reports for the prevalence
      of European descent populations. The results for the non-smoking group indicated
      no significant correlation between implant complications and a positive IL-1
      genotype. However, there was a clear association for heavy smokers between a
      positive IL-1 genotype and implant complications. 6 of 12 or half of the heavy
      smokers and IL-1 genotype-positive patients had either an implant failure, i.e.
      loss of implant, or a biologic complication during the follow-up period.
      CONCLUSIONS: These findings have led to the conclusion that there is a
      synergistic effect between a positive IL-1 genotype and smoking that puts dental
      implants at a significantly higher risk of developing biologic complications
      during function.

PMID- 15248874
TI  - Biomechanical aspects of marginal bone resorption around osseointegrated
      implants: considerations based on a three-dimensional finite element analysis.
AB  - OBJECTIVES: Although bone loss around implants is reported as a complication when
      it progresses uncontrolled, resorption does not always lead to implant loss, but
      may be the result of biomechanical adaptation to stress. To verify this
      hypothesis, a three-dimensional finite element analysis was performed and the
      influence of marginal bone resorption amount and shape on stress in the bone and
      implant was investigated. MATERIAL AND METHODS: A total of nine bone models with
      an implant were created: a non-resorption (Base) model and eight variations, in
      which three different resorption depths were combined with pure vertical or
      conical (vertical-horizontal) resorption. Axial and buccolingual forces were
      applied independently to the occlusal node at the center of the superstructure.
      RESULTS: Regardless of load direction, bone stresses were higher in the pure
      vertical resorption (A) models than in the Base model, and increased with
      resorption depth. However, cortical bone stress was much lower in the conical
      resorption models than in both the Base and A models of the same resorption
      depth. An opposite tendency was observed in the cancellous bone under
      buccolingual load. Under buccolingual load, highest stress in the implant
      increased linearly with the resorption depth for all the models and its location
      approached the void existing below the abutment screw. CONCLUSIONS: The results
      of this analysis suggest that a certain amount of conical resorption may be the
      result of biomechanical adaptation of bone to stress. However, as bone resorption
      progresses, the increasing stresses in the cancellous bone and implant under
      lateral load may result in implant failure.

PMID- 15248875
TI  - Astra Tech and Branemark system implants: a 5-year prospective study of marginal
      bone reactions.
AB  - This paper describes the 5-year results of a comparative study between Astra Tech
      and Branemark system implants. The aim was to compare the systems primarily with
      regard to bone level changes, and also with regard to other variables of
      interest. Sixty-six patients with edentulous jaws were included in the study.
      Randomisation schedules were used to allocate the patients to the two implant
      systems. 184 Astra Tech implants with a titanium-blasted surface and 187
      Branemark implants with a turned surface were used. The implants were inserted
      with a two-stage technique and the insertion followed the routines for the
      respective implant system. All patients were provided with full-arch fixed
      bridges. All patients were followed up with clinical and radiographic
      examinations from fixture insertion to the 5-year follow-up. The total mean bone
      level change in the upper jaw between fixture insertion and the 5-year
      examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the
      Branemark implants. The corresponding values for the lower jaw were -1.06+/-0.19
      for Astra and -1.38+/-0.17 for Branemark. The major postoperative changes of the
      marginal bone level took place between fixture insertion and baseline. During
      this period, there was also a different pattern of bone remodelling between the
      implant systems. Between baseline (prosthesis connection) and the 5-year
      examination, the marginal bone level changes were small, with no difference
      between the implant systems. The implant stability was examined with the
      supraconstructions removed. At the 5-year examination, the survival rate for
      Astra Tech implants was 98.4% and for the Branemark implants it was 94.6%. The
      difference was not statistically significant.

PMID- 15248876
TI  - A controlled clinical trial of implant-retained mandibular overdentures: 10
      years' results of clinical aspects and aftercare of IMZ implants and Branemark
      implants.
AB  - The aim of this prospective randomized controlled clinical trial was to evaluate
      the clinical outcomes and prosthetic aftercare of edentulous patients with a
      mandibular overdenture retained by two IMZ implants or two Branemark implants
      during a 10-year period. Patients were allocated to the IMZ group (n=29) or the
      Branemark group (n=32) by a computerized balancing method. In the IMZ group, four
      implants were lost during the 10-year follow-up (survival rate: 93%). In the
      Branemark group, nine implants were lost (survival rate: 86%). All patients were
      re-operated successfully. Multiple prosthetic revisions were necessary in both
      groups; especially the precision attachment system in the overdenture (23% of the
      total number of revisions) and the denture base and teeth (26% of the total
      number of revisions) were subject to frequent fracture. From this study, it can
      be concluded that both the IMZ implant and the Branemark implant systems
      supporting an overdenture are functioning well after 10 years of follow-up. There
      are no indications of a worsening of clinical or radiographical state after 10
      years.

PMID- 15248877
TI  - Resonance frequency analysis of implants subjected to immediate or early
      functional occlusal loading. Successful vs. failing implants.
AB  - OBJECTIVES: The objective of this study was to analyze the development of implant
      stability by repeated resonance frequency analysis (RFA) measurements during 1
      year in 23 patients treated according to an immediate/early-loading protocol. The
      objective was also to evaluate the possible differences between failing and
      successful implants. MATERIAL AND METHODS: Eighty-one Branemark System implants
      were placed in 23 patients for immediate/early-occlusal loading in all jaw
      regions. Thirty of the implants were placed in extraction sockets and 62 were
      subjected to GBR procedures. Apart from clinical and radiographic examinations,
      the patients were followed with RFA at placement, prosthesis connection and after
      1-3, 6 and 12 months. Statistical analyses were carried out to study the possible
      differences between implants that failed during the study period and implants
      that remained successful. RESULTS: Nine implants failed (11.2%) during the 1 year
      of loading. RFA showed a distinct different pattern between the implants that
      remained stable and the implants that were lost. The implants that failed during
      the course of the study showed a significantly lower stability already after 1
      month. CONCLUSION: Within the limitations of this study, it is concluded that
      failing implants show a continuous decrease of stability until failure. Low RFA
      levels after 1 and 2 months seem to indicate an increased risk for future
      failure. This information may be used to avoid implant failure in the future by
      unloading implants with decreasing degree of stability with time as diagnosed
      with the RFA technique.

PMID- 15248878
TI  - A comparative study of barrier membranes as graft protectors in the treatment of
      localized bone defects. An experimental study in a canine model.
AB  - Guided bone regeneration is a predictable and well-documented surgical approach
      for the treatment of deficient alveolar ridges prior to endosseous implant
      placement. The purpose of this study was to compare a new resorbable membrane
      (GORE RESOLUT ADAPT Regenerative Membrane, i.e. 67% glycolide (PGA) : 33%
      trimethyline carbonate (TMC)) with Bio-Gide, a resorbable collagen membrane. Five
      canines were used in the study. Three saddle-type osseous defects were created
      bilaterally in edentulous areas of the mandible. The defects were filled with
      assayed, canine demineralized freeze-dried bone (DFDB) in a thermoplastic gelatin
      matrix. Using a randomized block design, four sites were covered with PGA : TMC
      membranes of four different porosities, one site was covered with a collagen
      membrane and one site consisted of DFDB alone (control). At 3 months, the animals
      were euthanized and the mandibles were removed en bloc for laboratory processing.
      A total of 30 sites were reviewed microradiographically and underwent
      histomorphometric analysis for bone regeneration, soft tissue presence and
      remaining graft material. All sites exhibited uneventful healing. A significantly
      higher percentage of bone regeneration was seen in the sites protected by the PGA
      : TMC membrane. A higher component of soft tissue was visible beneath the
      collagen membrane as compared with the PGA : TMC membrane. The control sites
      exhibited noticeable deformation of the regenerated bone secondary to collapse of
      the overlying periosteum. The authors conclude that the PGA : TMC membrane
      protected the DFDB-filled defect and allowed a greater amount of bone
      regeneration than the defect protected by the collagen membrane or the control.

PMID- 15248879
TI  - Biocompatibility of various collagen membranes in cultures of human PDL
      fibroblasts and human osteoblast-like cells.
AB  - The aim of the present study was to evaluate the biocompatibility of differently
      cross-linked collagen membranes in cultures of human PDL fibroblasts and human
      osteoblast-like cells. Four collagen membranes [BioGide (BG), BioMend (BM), Ossix
      (OS) and TutoDent (TD)] were tested. Cells plated on culture dishes (CD) served
      as positive controls. Six specimens of each membrane were incubated with (1)
      human PDL fibroblasts [2 x 10(4) cells] (n=24), and (2) human osteoblast-like
      cells (SaOs-2) [2 x 10(4) cells] (n=24) under standardized conditions. After 7
      days, adherent cells were stained with hematoxylin and counted using a reflected
      light microscope and the cell density per square millimeter was calculated.
      Additionally, cell morphology was investigated using scanning electron microscopy
      (SEM). Cell counts were presented as means and standard deviations (cells/mm(2))
      and analyzed for statistical difference using the Wilcoxon test: (1) CD (434+/
      76)>BG (64+/-19)=OS (61+/-8)>TD (44+/-4)>BM (12+/-5); (2) CD (453+/-92)>BG (94+/
      46)=TD (84+/-49)>OS (41+/-23)>BM (0). SEM examination revealed that PDL
      fibroblasts adherent on BG, TD and OS appeared spindle-shaped and flat, like
      cells on CD. SaOs-2 osteoblasts adherent on CD were star shaped and flat, but
      mostly round in shape on BG, OS and TD. BM appeared to be incompatible with the
      attachment and proliferation of SaOs-2 cells; however, a few PDL fibroblasts were
      found in a round shape. Within the limits of the present study, it was concluded
      that (i) BG, TD and OS promoted, and (ii) BM inhibited the attachment and
      proliferation of human PDL fibroblasts and human SaOs-2 osteoblasts.

PMID- 15248880
TI  - Area moments of inertia as a measure of the mandible stiffness of the implant
      patient.
AB  - It was hypothesized that the bending stiffness of the mandible is an important
      biomechanical parameter in implant dentistry. It was shown how this bending
      stiffness can be estimated by means of the principal area moments of inertia of
      the cortical and cancellous cross-sections as obtained by computed tomography,
      some image processing and subsequent calculation. It was found that the
      contribution of the cancellous bone to the bending stiffness is normally
      insignificant and that the principal area moments of inertia of the cortical
      cross-section show large variations, depending on the degree of resorption. It
      was furthermore found that the variations in the principal area moments of
      inertia of the cortical cross-section in one and the same potential implant
      patient were minor. Finally, in a three-dimensional finite element study, it was
      found that the peak bone stresses adjacent to implants, resulting from a
      standardized load at the distal end of an implant-supported bridge, were
      inversely related to the magnitude of the principal area moment of inertia about
      the horizontal axis of the cortical cross-section. It was concluded that the
      principal area moments of inertia of the cortical cross-section and the
      angulation of the principal axes of inertia might be useful as a quantitative
      characterization of the mandible stiffness in clinical research and perhaps also
      in clinical practice.

PMID- 15248881
TI  - Dynamic fatigue resistance of implant-abutment junction in an internally notched
      morse-taper oral implant: influence of abutment design.
AB  - PURPOSE: To compare dynamic fatigue resistance of one- and two-piece abutments
      connected to internally notched morse-taper oral implants. MATERIAL AND METHODS:
      Sixteen synOcta ITI implants were tightened into two metal models. SynOcta
      abutments for cement-retained restorations and solid abutments were divided into
      two equal groups and were torque-tightened into the implants. Each implant
      received a cement-retained crown. Cyclic dynamic axial and lateral peak loads of
      75+/-5 N were applied on the implants for a duty of 500,000 cycles at 0.5 Hz, and
      at an angle of 20 degrees. Prior to the experiments and at each 100,000 cycles of
      loading, periotest values (PTVs) were measured. Removal torque values (RTVs) of
      the abutments were also measured with a custom-made torque device at the
      termination of the experiment. RESULTS: All abutments and implants were
      clinically immobile and without any signs of mechanical failure. The final PTVs
      for both abutments were similar and the difference between groups was
      insignificant (P>0.05). The RTVs of solid abutments were significantly higher
      than synOcta abutments (P<0.05). CONCLUSION: Predictable long-term clinical
      results can be achieved with solid abutments and synOcta abutments for cement
      retained restorations. Solid abutments possess higher removal torque resistance
      than synOcta abutments when connected to synOcta ITI implants.

PMID- 15248882
TI  - Cement fixation and screw retention: parameters of passive fit. An in vitro study
      of three-unit implant-supported fixed partial dentures.
AB  - It is generally assumed that passively fitting superstructures are a prerequisite
      for long-lasting implant success. In the study presented, the strain development
      of three-unit implant fixed partial dentures (FPDs) was evaluated at the bone
      surrounding the implant and on the superstructure using a strain gauge technique.
      Six groups of three-unit FPDs representing the commonly used techniques of bridge
      fabrication were investigated with 10 samples each, in order to quantify the
      influence of impression technique, mode of fabrication and retention mechanism on
      superstructure fit. Two ITI implants (Straumann, Waldenburg, Switzerland) were
      anchored in a measurement model according to a real-life patient situation and
      strain gauges were fixed mesially and distally adjacent to the implants and on
      the bridge pontics. The developing strains were recorded during cement setting
      and screw fixation. For statistical analysis, multivariate two sample tests were
      performed setting the level of significance at P=0.1. None of the investigated
      bridges revealed a truly passive fit without strains occurring. About 50% of the
      measured strains were found to be due to impression taking and model fabrication,
      whereas the remaining 50% were related to laboratory inaccuracies. The two
      impression techniques used did not reveal any significant differences in terms of
      precision. Both modes of fixation--i.e. cement and screw retention--provoked
      equally high stress levels. In the fabrication of screw-retained FPDs, similar
      results were obtained from the use of burn-out plastic copings and the technique
      of casting wax moulds to premachined components. Bonding bridge frames onto gold
      cylinders directly on the implants significantly reduces strain development.

PMID- 15248883
TI  - Influence of implant taper on the primary and secondary stability of
      osseointegrated titanium implants.
AB  - OBJECTIVES: The study presented was designed to analyse the mechanical
      performance and the primary and secondary stability characteristics of endosseous
      titanium implants with 1 degree (EXP1) and 2 degrees (EXP2) of taper when
      compared with the standard Branemark design (Nobel Biocare AB, Gothenburg,
      Sweden). MATERIALS AND METHODS: One pair of 10 mm EXP1 and control implants were
      placed in the femoral condyles of six rabbits. Paired 6 mm EXP1 and control
      implants and 6 mm EXP2 and control implants were placed in the tibial metaphysis.
      The control implants used were 4 mm diameter standard Branemark implants, the
      same length as the test implants. At placement, insertion torque (IT) and
      resonance frequency analysis (RFA) measurements were performed. Six weeks
      postoperatively when the animals were killed, RFA and removal torque (RT)
      measurements were made. RESULTS: At placement, significantly higher IT was needed
      to insert the EXP implants compared with the controls. RFA values were
      significantly higher for EXP1 implants placed in the tibia but not in the femur.
      In pooling data from the femur and tibia there was a significant difference. The
      EXP2 implants failed to insert fully and demonstrated a lower RFA value than may
      have been expected due to the exposed threads, although this difference was not
      statistically significant. CONCLUSIONS: The results from the present study showed
      that 1 degrees of taper results in a better primary stability compared with the
      standard Branemark design. There was no evidence that the tapered design caused
      negative bone tissue reactions. All the implants gained in stability during the
      healing period.

PMID- 15248884
TI  - Force transmission of one- and two-piece morse-taper oral implants: a nonlinear
      finite element analysis.
AB  - PURPOSE: To compare force transmission behaviors of one-piece (1-P) and two-piece
      (2-P) morse-taper oral implants. MATERIAL AND METHODS: A three-dimensional finite
      element model of a morse-taper oral implant and a solid abutment was constructed
      separately. The implant-abutment complex was embedded in a phi 1.5 cm x 1.5 cm
      acrylic resin cylinder. Vertical and oblique forces of 50 N and 100 N were
      applied on the abutment and solved by two different analyses. First, contact
      analysis was performed in the implant-abutment complex to evaluate a 2-P implant.
      Then, the components were bonded with a separation force of 10(20) N to analyze a
      1-P implant. RESULTS: Von Mises stresses in the implant, principal stresses, and
      displacements in the resin were the same for both designs under vertical loading.
      Under oblique loading, principal stresses and displacement values in the resin
      were the same, but the magnitudes of Von Mises stresses were higher in the 2-P
      implant. The principal stress distributions around both implants in the acrylic
      bone were similar under both loading conditions. CONCLUSION: 2-P implants
      experience higher mechanical stress under oblique loading. Nevertheless, the 1-P-
      or 2-P morse-taper nature of an implant is not a decisive factor for the
      magnitude and distribution of stresses, and displacements in supporting tissues.

PMID- 15248885
TI  - Study on the necessity for cross-section imaging of the posterior mandible for
      treatment planning of standard cases in implant dentistry.
AB  - OBJECTIVE: To investigate whether cross-section imaging influences the planning
      and therapy of standard implant cases in the posterior mandible. MATERIAL AND
      METHODS: In a prospective study conducted over 16 months, the planned treatment
      (standard implant therapy without bone augmentation procedures in the premolar
      and molar regions of the mandible) was compared with the postoperative result in
      50 randomly selected patients. Clinical examinations and panoramic radiographs
      were performed pre- and postoperatively, whereas cross-sectional tomography was
      performed only preoperatively. RESULTS: The vertical magnification factor in the
      panoramic radiographs was very constant pre- and postoperatively with 1 : 1.27
      and in the spiral tomograms with 1 : 1.52. In 11 of 77 implant sites, the
      mandibular canal could not be evaluated in the spiral tomograms. The additional
      information from cross-sectional spiral tomography did not influence the original
      planning in 74 of 77 (96.1%) implant sites. Based on the postoperative panoramic
      radiograph, the average distance from the tip of the implants to the mandibular
      canal was 3.04+/-2.06 mm. In two cases (2.6%), transient postoperative altered
      tactile sensation of the mental nerve was found. CONCLUSION: The information from
      preoperative cross-sectional spiral tomography has minor impact on treatment
      planning in standard implant cases in mandibular premolar and molar regions. The
      clinical examination provides sufficient information for selecting implant
      diameter and the panoramic radiograph provides sufficient information for implant
      length selection.

PMID- 15248886
TI  - Patient experience of, and satisfaction with, delayed-immediate vs. delayed
      single-tooth implant placement.
AB  - OBJECTIVES: Recent investigations have focused on patients' subjective assessment
      of implant treatment. The aim of this study was to compare the patients'
      experience of surgical and prosthetic procedures, as well as satisfaction with
      function and aesthetics following single-tooth replacements mounted to early vs.
      delayed placed dental implants. MATERIAL AND METHODS: Forty-six patients were
      treated with a single-tooth implant in the anterior or premolar region. Twenty
      three implants were placed on average 10 days after tooth extraction (Im), while
      23 implants were placed approximately 3 months after tooth extraction (De). Forty
      one patients completed a questionnaire regarding the treatment using visual
      analog scales (VAS) and check boxes 16-18 months after delivery of the
      restoration. RESULTS: In all, 90% of the respondents rated 88 or higher on the
      VAS regarding satisfaction with the crown. Satisfaction with the restoration in
      general and the appearance was significantly greater in the Im group than in the
      De group (96 vs. 93; P<0.02). Assessment of the implant surgery was not
      significantly different between the delayed-immediate and the delayed group.
      Approximately 25% of the patients experienced unpleasantness in relation to the
      prosthetic procedures, and in 8 of 11 cases, impression taking was the cause.
      When evaluating satisfaction with the overall implant treatment, the VAS scores
      for the delayed-immediate group were significantly higher than for the delayed
      group (96 vs. 90; P<0.02). CONCLUSION: The patients in the present study were
      highly satisfied with the outcome of the treatment and experienced it to be
      without significant unpleasantness irrespective of the treatment concept.

PMID- 15248891
TI  - Abstracts of the 8th World Congress on Clinical Pharmacology & Therapeutics.
      August 1-6, 2004. Brisbane, Australia.

PMID- 15248892
TI  - The student and the ovum: the lack of autonomy and informed consent in trading
      genes for tuition.
AB  - Rising tuition costs have forced university students to become creative in
      finding ways to fund their education. Some female university students have
      decided that ova donation may be an acceptable alternative in which to pay for
      their tuition. This alternative presents itself because of the insufficient
      number of ova available for assisted reproduction and emerging stem cell
      technologies. Young female university students are encouraged by Internet sources
      and respectable electronic and print media to donate their ova in the cause of
      assisted reproduction for monetary compensation. While university students
      generally exhibit autonomy, the constraining influence of their financial
      predicament compromises the elements of informed consent (voluntariness,
      competence, capacity, understanding, and disclosure) as to their making an
      autonomous decision in regard to egg donation. Thus, any moral possibility of
      giving informed consent is negated. Informed consent can only occur through
      autonomy. A female university student in need of financial resources to pay for
      her education cannot make an autonomous choice to trade her genes for tuition.
      Donated ova are not only needed for assisted reproduction, but for stem cell
      technologies. While the long-term health of women who donate their ova is of
      concern (a potential risk of cancer after long term use of ovulation induction),
      of equal concern is the possibility of a growth in the trade of ova targeting
      third world and Eastern European women where the precedence for autonomy and
      informed consent is not well established.

PMID- 15248893
TI  - Dimensions of oral health related quality of life measured by EQ-5D+ and OHIP-14.
AB  - BACKGROUND: The aims of the study were to compare the dimensions of oral-health
      related quality-of-life measured by a generic health state measure, the EuroQol,
      and a specific oral health measure, the Oral Health Impact Profile. METHODS: Data
      were collected in 2001-02 from a random sample of South Australian dentists using
      mailed self-complete questionnaires. Dentists recorded the diagnosis of dental
      problems and provided patients with self-complete questionnaires to record the
      nature, severity and duration of symptoms using the EuroQol (EQ-5D+) and 14-item
      version of the Oral Health Impact Profile (OHIP-14) instruments. RESULTS: Data
      were available from 375 patients (response rate = 72%). The EuroQol items of
      mobility, self care and usual activities formed a separate cluster of variables,
      as did anxiety/depression and cognition, while pain clustered with items from the
      OHIP physical pain subscale. OHIP items tended to form clusters consistent with
      the subscales of social disability, physical disability, physical pain,
      functional limitation and psychological discomfort. The OHIP handicap items
      clustered between the OHIP social disability and physical disability subscales.
      The OHIP psychological disability items split between the social disability and
      psychological discomfort subscales. CONCLUSIONS: The observed clusters of
      variables empirically supported most of the conceptual dimensions of the OHIP.
      Both instruments covered symptom experience of pain indicating overlapping
      domains. However there was partial separation of the generic and specific items,
      EuroQol covered daily activities such as self-care and usual activities and OHIP
      covered oral health-specific aspects of functional limitation and physical
      disability as well as psychological and social aspects of disability and
      handicap.

PMID- 15248894
TI  - Facilitating post traumatic growth.
AB  - BACKGROUND: Whilst negative responses to traumatic injury have been well
      documented in the literature, there is a small but growing body of work that
      identifies posttraumatic growth as a salient feature of this experience. We
      contribute to this discourse by reporting on the experiences of 13 individuals
      who were traumatically injured, had undergone extensive rehabilitation and were
      discharged from formal care. All participants were injured through involvement in
      a motor vehicle accident, with the exception of one, who was injured through
      falling off the roof of a house. METHODS: In this qualitative study, we used an
      audio-taped in-depth interview with each participant as the means of data
      collection. Interviews were transcribed verbatim and analysed thematically to
      determine the participants' unique perspectives on the experience of recovery
      from traumatic injury. In reporting the findings, all participants' were given a
      pseudonym to assure their anonymity. RESULTS: Most participants indicated that
      their involvement in a traumatic occurrence was a springboard for growth that
      enabled them to develop new perspectives on life and living. CONCLUSION: There
      are a number of contributions that health providers may make to the recovery of
      individuals who have been traumatically injured to assist them to develop new
      views of vulnerability and strength, make changes in relationships, and
      facilitate philosophical, physical and spiritual growth.

PMID- 15248895
TI  - The Medicare Health Outcomes Survey program: overview, context, and near-term
      prospects.
AB  - In 1996, the Centers for Medicare & Medicaid Services (CMS) initiated the
      Medicare Health Outcomes Survey (HOS). It is the first national survey to measure
      the quality of life and functional health status of Medicare beneficiaries
      enrolled in managed care. The program seeks to gather valid and reliable health
      status data in Medicare managed care for use in quality improvement activities,
      public reporting, plan accountability and improving health outcomes based on
      competition. The context that led to the development of the HOS was formed by the
      convergence of the following factors: 1) a recognized need to monitor the
      performance of managed care plans, 2) technical expertise and advancement in the
      areas of quality measurement and health outcomes assessment, 3) the existence of
      a tested functional health status assessment tool (SF-36)1, which was valid for
      an elderly population, 4) CMS leadership, and 5) political interest in quality
      improvement. Since 1998, there have been six baseline surveys and four follow up
      surveys. CMS, working with its partners, performs the following tasks as part of
      the HOS program: 1) Supports the technical/scientific development of the HOS
      measure, 2) Certifies survey vendors, 3) Collects Health Plan Employer Data and
      Information Set(HEDIS)2 HOS data, 4) Cleans, scores, and disseminates annual
      rounds of HOS data, public use files and reports to CMS, Quality Improvement
      Organizations (QIOs), Medicare+Choice Organizations (M+COs), and other
      stakeholders, 5) Trains M+COs and QIOs in the use of functional status measures
      and best practices for improving care, 6) Provides technical assistance to CMS,
      QIOs, M+COs and other data users, and 7) Conducts analyses using HOS data to
      support CMS and HHS priorities.CMS has recently sponsored an evaluation of the
      HOS program, which will provide the information necessary to enhance the future
      administration of the program. Information collected to date reveals that the HOS
      program is a valuable tool that provides a rich set of data that is useful for
      quality monitoring and improvement efforts. To enhance the future of the HOS
      program, many stakeholders recommend the implementation of incentives to
      encourage the use of the data, while others identify the need to monitor the
      health status of plan disenrollees.Overall, the HOS program represents an
      important vehicle for collecting outcomes data from Medicare beneficiaries. The
      new Medicare Prescription Drug, Improvement, and Modernization Act (2003)
      mandates the collection and use of data for outcomes measurement. Consequently,
      it is important to improve HOS to most effectively meet the mandate.

PMID- 15248896
TI  - Mutation in mitochondrial complex I ND6 subunit is associated with defective
      response to hypoxia in human glioma cells.
AB  - BACKGROUND: Hypoxia-tolerant human glioma cells reduce oxygen consumption rate in
      response to oxygen deficit, a defense mechanism that contributes to survival
      under moderately hypoxic conditions. In contrast, hypoxia-sensitive cells lack
      this ability. As it has been previously shown that hypoxia-tolerant (M006x,
      M006xLo, M059K) and -sensitive (M010b) glioma cells express differences in
      mitochondrial function, we investigated whether mitochondrial DNA-encoded
      mutations are associated with differences in the initial response to oxygen
      deficit. RESULTS: The mitochondrial genome was sequenced and 23 mtDNA alterations
      were identified, one of which was an unreported mutation (T-C transition in base
      pair 14634) in the hypoxia-sensitive cell line, M010b, that resulted in a single
      amino acid change in the gene encoding the ND6 subunit of NADH:ubiquinone
      oxidoreductase (Complex I). The T14634C mutation did not abrogate ND6 protein
      expression, however, M010b cells were more resistant to rotenone, an agent used
      to screen for Complex I mutations, and adriamycin, an agent activated by redox
      cycling. The specific function of mtDNA-encoded, membrane-embedded Complex I ND
      subunits is not known at present. Current models suggest that the transmembrane
      arm of Complex I may serve as a conformationally driven proton channel. As
      cellular respiration is regulated, in part, by proton flux, we used homology
      based modeling and computational molecular biology to predict the 3D structure of
      the wild type and mutated ND6 proteins. These models predict that the T14634C
      mutation alters the structure and orientation of the trans-membrane helices of
      the ND6 protein. CONCLUSION: Complex I ND subunits are mutational hot spots in
      tumor mtDNA. Genetic changes that alter Complex I structure and function may
      alter a cell's ability to respond to oxygen deficit and consolidate hypoxia
      rescue mechanisms, and may contribute to resistance to chemotherapeutic agents
      that require redox cycling for activation.

PMID- 15248897
TI  - Inhibition of macrophage migration inhibitory factor decreases proliferation and
      cytokine expression in bladder cancer cells.
AB  - BACKGROUND: The importance of various inflammatory cytokines in maintaining tumor
      cell growth and viability is well established. Increased expression of the
      proinflammatory cytokine macrophage migration inhibitory factor (MIF) has
      previously been associated with various types of adenocarcinoma. METHODS: MIF IHC
      was used to localize MIF in human bladder tissue. ELISA and Western blot analysis
      determined the synthesis and secretion of MIF by human bladder transitional cell
      carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate
      (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression
      were analyzed. RESULTS: Human bladder cancer cells (HT-1376) secrete detectable
      amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense
      reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression
      and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the
      invariant chain, CD74 and the major cell surface receptor for HA, CD44.
      CONCLUSIONS: This study is the first to report MIF expression in the human
      bladder and these findings support a role for MIF in tumor cell proliferation.
      Since MIF participates in the inflammatory response and bladder cancer is
      associated with chronic inflammatory conditions, these new findings suggest that
      neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for
      bladder carcinoma.

PMID- 15248898
TI  - BAK overexpression mediates p53-independent apoptosis inducing effects on human
      gastric cancer cells.
AB  - BACKGROUND: BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic
      gene of the Bcl-2 family. It has been reported that gastric tumors have reduced
      BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK
      gene have been identified in human gastrointestinal cancers, suggesting that a
      perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of
      gastric cancer. In this study, we explored the therapeutic effects of gene
      transfer mediated elevations in BAK expression on human gastric cancer cells in
      vitro. METHODS: Eukaryotic expression vector for the BAK gene was constructed and
      transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28
      (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene
      expression. Cell growth activities were detected by MTT colorimetry and flow
      cytometry, while apoptosis was assayed by electronic microscopy and TUNEL.
      Western Blotting and colorimetry investigated cellular caspase-3 activities.
      RESULTS: BAK gene transfer could result in significant BAK overexpression,
      decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in
      gastric cancer cells. In transferred cells, inactive caspase-3 precursor was
      cleaved into the active subunits p20 and p17, during BAK overexpression-induced
      apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN
      45), or in p53 mutant-type (MKN-28) gastric cancer cells. CONCLUSIONS: The data
      presented suggests that overexpression of the BAK gene can lead to apoptosis of
      gastric cancer cells in vitro, which does not appear to be dependent on p53
      status. The action mechanism of BAK mediated apoptosis correlates with activation
      of caspase-3. This could be served as a potential strategy for further
      development of gastric cancer therapies.

PMID- 15248899
TI  - Meta-analytic methods for pooling rates when follow-up duration varies: a case
      study.
AB  - BACKGROUND: Meta-analysis can be used to pool rate measures across studies, but
      challenges arise when follow-up duration varies. Our objective was to compare
      different statistical approaches for pooling count data of varying follow-up
      times in terms of estimates of effect, precision, and clinical interpretability.
      METHODS: We examined data from a published Cochrane Review of asthma self
      management education in children. We selected two rate measures with the largest
      number of contributing studies: school absences and emergency room (ER) visits.
      We estimated fixed- and random-effects standardized weighted mean differences
      (SMD), stratified incidence rate differences (IRD), and stratified incidence rate
      ratios (IRR). We also fit Poisson regression models, which allowed for further
      adjustment for clustering by study. RESULTS: For both outcomes, all methods gave
      qualitatively similar estimates of effect in favor of the intervention. For
      school absences, SMD showed modest results in favor of the intervention (SMD 
      0.14, 95% CI -0.23 to -0.04). IRD implied that the intervention reduced school
      absences by 1.8 days per year (IRD -0.15 days/child-month, 95% CI -0.19 to 
      0.11), while IRR suggested a 14% reduction in absences (IRR 0.86, 95% CI 0.83 to
      0.90). For ER visits, SMD showed a modest benefit in favor of the intervention
      (SMD -0.27, 95% CI: -0.45 to -0.09). IRD implied that the intervention reduced ER
      visits by 1 visit every 2 years (IRD -0.04 visits/child-month, 95% CI: -0.05 to 
      0.03), while IRR suggested a 34% reduction in ER visits (IRR 0.66, 95% CI 0.59 to
      0.74). In Poisson models, adjustment for clustering lowered the precision of the
      estimates relative to stratified IRR results. For ER visits but not school
      absences, failure to incorporate study indicators resulted in a different
      estimate of effect (unadjusted IRR 0.77, 95% CI 0.59 to 0.99). CONCLUSIONS:
      Choice of method among the ones presented had little effect on inference but
      affected the clinical interpretability of the findings. Incidence rate methods
      gave more clinically interpretable results than SMD. Poisson regression allowed
      for further adjustment for heterogeneity across studies. These data suggest that
      analysts who want to improve the clinical interpretability of their findings
      should consider incidence rate methods.

PMID- 15248900
TI  - Beckman Access versus the Bayer ACS:180 and the Abbott AxSYM cardiac Troponin-I
      real-time immunoassays: an observational prospective study.
AB  - BACKGROUND: Reliability of cardiac troponin-I assays under real-time conditions
      has not been previously well studied. Most large published cTnI trials have
      utilized protocols which required the freezing of serum (or plasma) for delayed
      batch cTnI analysis. We sought to correlate the presence of the acute ischemic
      coronary syndrome (AICS) to troponin-I values obtained in real-time by three
      random-mode analyzer immunoassay systems: the Beckman ACCESS (BA), the Bayer
      ACS:180 (CC) and the Abbott AxSYM (AX). METHODS: This was an observational
      prospective study at a university tertiary referral center. Serum from a
      convenience sampling of telemetry patients was analyzed in real-time for troponin
      I by either the BA-CC (Arm-1) or BA-AX (Arm-2) assay pairs. Presence of the AICS
      was determined retrospectively and then correlated with troponin-I results.
      RESULTS: 100 patients were enrolled in Arm-1 (38 with AICS) and 94 in Arm-2 (48
      with AICS). The BA system produced 51% false positives in Arm-1, 44% in Arm-2,
      with negative predictive values of 92% and 100% respectively. In Arm-1, the BA
      and the CC assays had sensitivities of 97% and 63% and specificities of 18% and
      87%. In Arm-2, the BA and the AX assays had sensitivities of 100% and 83% and
      specificities of 11% and 78%. CONCLUSIONS: In real-time analysis, the performance
      of the AxSYM and ACS:180 assay systems produced more accurate troponin-I results
      than the ACCESS system.

PMID- 15248901
TI  - Yersinia enterocolitica type III secretion: evidence for the ability to transport
      proteins that are folded prior to secretion.
AB  - BACKGROUND: Pathogenic Yersinia species (Y. enterocolitica, Y. pestis, Y.
      pseudotuberculosis) share a type three secretion system (TTSS) which allows
      translocation of effector proteins (called Yops) into host cells. It is believed
      that proteins are delivered through a hollow needle with an inner diameter of 2-3
      nm. Thus transport seems to require substrates which are essentially unfolded.
      Recent work from different groups suggests that the Yersinia TTSS cannot
      accommodate substrates which are folded prior to secretion. It was suggested that
      folding is prevented either by co-translational secretion or by the assistance of
      specific Yop chaperones (called Sycs). RESULTS: In this study we have fused YopE
      secretion signals of various length to the mouse dihydrofolate reductase (DHFR)
      in order to analyse the DHFR folding state prior to secretion. We could
      demonstrate that secretion-deficient as well as secretion-competent YopE-DHFR
      fusions complexed to SycE can be efficiently purified from Yersinia cytosol by
      affinity chromatography using methotrexate-agarose. This implies the folding of
      the DHFR fusion moiety despite SycE binding and contradicts the previously
      presented model of folding inhibition by chaperone binding. Secretion-deficient
      YopE-DHFR fusions caused severe jamming of the TTSS. This observation contradicts
      the co-translational secretion model. CONCLUSIONS: We present evidence that the
      Yersinia TTSS is familiar with the processing of transport substrates which are
      folded prior to secretion. We therefore predict that an unfoldase is involved in
      type III secretion.

PMID- 15248902
TI  - Delayed impact: ISI's citation tracking choices are keeping scientists in the
      dark.

PMID- 15248903
TI  - Target SNP selection in complex disease association studies.
AB  - BACKGROUND: The massive amount of SNP data stored at public internet sites
      provides unprecedented access to human genetic variation. Selecting target SNP
      for disease-gene association studies is currently done more or less randomly as
      decision rules for the selection of functional relevant SNPs are not available.
      RESULTS: We implemented a computational pipeline that retrieves the genomic
      sequence of target genes, collects information about sequence variation and
      selects functional motifs containing SNPs. Motifs being considered are gene
      promoter, exon-intron structure, AU-rich mRNA elements, transcription factor
      binding motifs, cryptic and enhancer splice sites together with expression in
      target tissue. As a case study, 396 genes on chromosome 6p21 in the extended HLA
      region were selected that contributed nearly 20,000 SNPs. By computer annotation
      ~2,500 SNPs in functional motifs could be identified. Most of these SNPs are
      disrupting transcription factor binding sites but only those introducing new
      sites had a significant depressing effect on SNP allele frequency. Other decision
      rules concern position within motifs, the validity of SNP database entries, the
      unique occurrence in the genome and conserved sequence context in other mammalian
      genomes. CONCLUSION: Only 10% of all gene-based SNPs have sequence-predicted
      functional relevance making them a primary target for genotyping in association
      studies.

PMID- 15248904
TI  - [Indomethacin induces apoptosis through inhibition of survivin regulated by beta
      catenin/TCF4 in human colorectal cancer cells].
AB  - BACKGROUND & OBJECTIVE: Although Wnt pathway plays important role in colorectal
      carcinogenesis, but the mechanism of this pathway in anti-apoptosis is not clear.
      This study is to investigate the molecular mechanism of Wnt pathway in anti
      apoptosis. METHODS: Survivin promoter region was constructed into luciferase
      reporter system (pGL3-sur1.8kb). The recombinants pGL3-sur1.8kb were
      cotransfected with pRL-SV40 into HCT116 cells and the activities were detected
      with Dual-luciferase reporter assay system. Cell apoptosis was analyzed by flow
      cytometry. Protein level of survivin and beta-catenin was detected by Western
      Blot. RESULTS: Survivin could be up-regulated by beta-catenin and down-regulated
      by TCF4DeltaN in transcriptional level. beta-catenin/TCF4 dependent apoptosis
      induced by indomethacin could suppress survivin transcription. Overexpression of
      survivin could partially recover the beta-catenin/TCF4 dependent apoptosis.
      CONCLUSION: Down-regulation of survivin affected by beta-catenin/TCF4 pathway
      plays an important role in apoptosis induced by NSAIDs indomethacin in HCT116
      cells. The beta-catenin/TCF4-survivin pathway may be a potential target in
      treatment of colon cancer.

PMID- 15248905
TI  - Construction of survivin siRNA expression vector and its regulation on cell cycle
      and proliferation in MCF-7 cells.
AB  - BACKGROUND & OBJECTIVE: Survivin is specifically overexpressed in tumor tissues.
      Many reports have shown that the abrogation of its functions is useful for tumor
      therapy. RNA interference is a new technique that proved to be effective for
      suppressing gene expression. The aim of this study was to construct a siRNA
      expression plasmid against gene survivin, and then to assess its functions on
      breast cancer cells MCF-7. METHODS: A survivin siRNA plasmid was constructed
      using a mU6pro vector contained U6 promotor, the expression change of survivin
      was examined by semi-quantitative reverse transcription polymerase chain reaction
      (RT-PCR) and Western blot analysis after the plasmid had been transfected into
      MCF-7 cells, and the effect of the plasmid on the cell cycle and cell
      proliferation was analyzed by flow cytometry and MTT method,respectively.
      RESULTS: Survivin siRNA plasmid knocked down survivin expression in MCF-7 cells
      obviously, arrested the cell cycle in G1 phase, inhibited the cell proliferation
      significantly, and promoted cell apoptosis in a tendency. CONCLUSION: Survivin
      expression was knocked down at mRNA and protein levels by RNAi.

PMID- 15248906
TI  - [Effects of hepatitis B virus X gene on p21(WAF1) expression through p53
      dependent and p53-independent pathways].
AB  - BACKGROUND & OBJECTIVE: It was reported that the hepatitis B virus X could
      inhibit the function of p53 and have contrary effects on p21(WAF1), a downstream
      gene of p53, but the mechanism is not clear up to now. So this study was designed
      to investigate HBx's effect on p21(WAF1) gene. METHODS: After co-transfection of
      sense or antisense wild type p53 gene (wtp53) with HBx into SMMC-7721 and HBx
      alone transfection into other hepatoma cell lines with different endogenous
      status of p53, we evaluated the luciferase expression level under the p21(WAF1)
      promoter by detecting the luciferase activity and alteration of cell cycle in
      these transfected cell lines by flow cytometry. Expressions of p53 and p21 (WAF1)
      in hepatoma cells after transfected with HBx were also estimated by Western blot
      analysis. RESULTS: The luciferase activity (1.007+/-0.098) in SMMC-7721 cells
      cotransfected with HBx and sense-wtp53 was higher than that in cells with wtp53
      gene alone (0.490+/-0.012, P< 0.05), and also was depressed in the other
      experimental groups transfected with HBx (P< 0.05). Western blot analysis showed
      that after transfected with HBx, p53 expression was elevated in all hepatoma cell
      lines with different endogenous status of p53, and the expression of p21(WAF1)
      and luciferase activity under the p21(WAF1) promoter (0.053+/-0.010 vs. 0.094+/
      0.013, P< 0.05) were both decreased in SMMC-7721 cells with low expression of
      p53, but relatively increased in HepG2 cell line with high expression of p53
      (1.252+/-0.052 vs. 0.767+/-0.031, P< 0.05). Flow cytometry showed that fewer SMMC
      7721 (42.31%) and Hep3B (36.96%) cells were arrested in G(0)/G(1) phase in
      transiently transfected HBx groups than in the control groups (47.10% and
      42.90%), which was the opposite case in HepG2 cell line (63.62% vs. 57.42%).
      Moreover, after stably transfected with pcDNA3HBx, HepG2 cells reduced in
      G(0)/G(1) phase in compared with the control group (57.31% vs 61.49%).
      CONCLUSION: HBx may not only increase the expression of p21(WAF1) by introducing
      the accumulation of p53 in cytoplasm but also inhibit the transcriptional
      activity of p21(WAF1) promoter in a p53-independent manner.

PMID- 15248907
TI  - [X protein variations of genotype B and C hepatitis B virus isolated from the
      patients with hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: X protein was one of the most important pathogens of
      hepatitis B virus (HBV), and was crucial in the carcinogenesis of HBV related
      hepatocellular carcinoma (HCC). It was demonstrated that the infection of
      genotype B or C HBV would result in different clinical manifestations and
      pathological characteristics in HCC patients, however, it was under elucidation
      whether these differences related to different genotypes of HBV X protein. This
      study was designed to investigate the amino acid differentiations of X proteins
      in standard genotype B or C HBV strains and the variations in HBV isolated from
      the HCC patients, and elucidate preliminarily the relationship between the
      genotype of HBV and carcinogenesis of HCC. METHODS: HBV X genes from the serum of
      twenty-two HBsAg positive HCC patients were amplified, cloned and sequenced.
      Genotyping of the X gene was carried out by Vector NTI6.0 software and the amino
      acid alignment among the standard and HCC originated X protein were done by
      DNAMAN software. RESULTS: Twenty-two HBV X genes were obtained and all of them
      could be categorized into genotype B or C. Besides of 14 amino acid
      differentiations within X protein between standard B and C HBV strains, HCC
      originated X protein of B and C genotype showed 4 consensus amino acid
      variations, and genotype C X protein showed additional 6 genotype-specific
      variations. All these differentiated and varied amino acids were located in the
      B, T cell epitopes and transactive or related regulatory regions. CONCLUSIONS: In
      addition to amino acid differentiations, X protein of genotype B or C HBV also
      showed genotype-specific variations in HCC patients. Amino acid differentiations
      and variations may result in the different immunocompetence and transactivation
      capacity between X proteins of genotype B and C.

PMID- 15248908
TI  - [Expression and significance of EGF mRNA and EGFR mRNA in hepatocellular
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Many evidences demonstrated that the epidermal growth
      factor receptor (EGFR) subfamily played an important role in they initiation and
      progression of various cancers. But it is not clear whether there is a
      relationship between EGFR and hepatocellular carcinoma (HCC). The aims of the
      present study were to explore the expression and significance of the epidermal
      growth factor (EGF) mRNA and EGFR mRNA in human HCC tissues. METHODS: Reverse
      transcription polymerase chain reaction (RT-PCR) was employed to determine the
      expression of EGF mRNA and EGFR mRNA in 60 HCC tissues and their adjacent liver
      tissues. RESULTS: The positive rate of EGF mRNA was significantly lower in the
      HCC tissue (60%, 36/60) than in the adjacent liver tissue (80%, 48/60) (P< 0.05).
      The positive rate of EGFR mRNA in the HCC tissue (60%, 36/60) was markedly higher
      than in the adjacent liver tissue (41.67%, 25/60) (P< 0.05). The expression of
      EGFR mRNA in the HCC tissue was significantly correlated with the clinical stage,
      the portal vein tumor thrombus, the presence of extrahepatic metastasis, and the
      recurrence of tumor, the number of tumor, but not correlated with the diameter of
      tumor, the level of serum alpha-fetoprotein (AFP), the differentiation of tumor
      and the liver cirrhosis in the adjacent tissue. The detectable rate of EGF mRNA
      was correlated with the diameter of tumor but not correlated with the clinical
      stage, the portal vein tumor thrombus, the presence of extrahepatic metastasis,
      the recurrence of tumor, the number of tumor, the level of serum AFP, the
      differentiation of tumor and the liver cirrhosis in the adjacent tissue.
      CONCLUSIONS: EGF may not be involved in the initiation and progression of HCC,
      whereas, EGFR relates to the initiation and progression and the recurrence of
      HCC. EGFR can be considered as a marker for predicting the metastasis and
      recurrence of HCC.

PMID- 15248909
TI  - [Epidemiological study of nasopharyngeal carcinoma risk in relatives of high-risk
      families in Guangdong].
AB  - BACKGROUND & OBJECTIVE: Familial clustering of NPC has been widely observed,
      however, related investigations were mainly involved in individual reports for
      high-risk families or case-control study with small sample size, so no quantitive
      evaluation for NPC risk in relatives of high-risk families documented in high
      risk area until now. The purpose of the study was to estimate NPC risk among
      relatives of high-risk pedigrees in Guangong province, so as to provide
      information for genetic epidemiology and clinical genetic consultation. METHODS:
      One hundred and thirteen high-risk pedigrees were collected in the Cancer Center
      of Sun Yat-sen University, and standardized incidence ratio (SIR) was used to
      estimate NPC risk of first degree relatives (FDR). RESULTS: NPC risk was
      significantly higher in first degree relatives that in general population, and
      SIR was 37.55; in addition, SIRs were 50.72, 79.64, 7.12, and 33.58 in their
      brothers, sisters, fathers, and mothers respectively. CONCLUSION: NPC risk of
      relatives in familial NPC pedigrees elevates 7.12 to 79.64 times in high-risk
      families.

PMID- 15248910
TI  - [Analysis of gene expression profiles among 3 epithelial ovarian tumor subtypes
      using cDNA and tissue microarrays].
AB  - BACKGROUND & OBJECTIVE: Ovarian cancer is the leading cause of death among the
      gynecological malignancy mainly due to lacking of effective early diagnostic
      methods. To identify novel candidate genes and further explore their clinical
      significance of epithelial ovarian tumors, we developed a new method in our
      laboratory by combining cDNA microarray with RNA in situ hybridization in frozen
      tissue microarray. METHODS: cDNA microarrays were used to seek differentially
      expressed genes among 3 subtypes of ovarian tumors (serous borderline ovarian
      tumors, serous ovarian cancers, and endometrioid ovarian carcinomas). RNA in situ
      hybridization in frozen tissue microarray was used to further confirm the
      findings from cDNA microarrays. RESULTS: In the study of cDNA microarray, 40
      genes and ESTs showed significant differential expression between low and high
      malignancy, as well as serous and endometrioid carcinomas. EPHB6, PTPRF, GFER,
      ERG25, PLRP1, FLJ22060, and WISP2 were further validated by RNA in situ
      hybridization in tissue microarray. CONCLUSIONS: cDNA microarray combined with
      RNA in situ hybridization in frozen tissue microarray is an ideal choice for
      identifying novel oncogenes. EPHB6, PTPRF, GFER, ERG25, PLRP1, FLJ22060, and
      WISP2 might become the new candidate oncogenes for epithelial ovarian cancer.

PMID- 15248911
TI  - [In vivo study of antitumor immune responses induced by anti-idiotypic minibody
      vaccine of ovarian cancer].
AB  - BACKGROUND & OBJECTIVE: 6B11 anti-idiotypic minibody can be constructed by fusion
      of anti-idiotypic single chain antibody (6B11scFv) to human IgG(1) hinge and CH3,
      which can simulate the function of ovarian carcinoma antigen. It has immune
      activity of both 6B11 and human immunoglobulin IgG(1) Fc. This study was designed
      to evaluate whether anti-tumor immune response can be induced in BALB/c mice
      immunized with 6B11anti-idiotypic minibody and explore its probability as ovarian
      cancer vaccine. METHODS: BALB/c mice were immunized repeatedly by 6B11 anti
      idiotypic minibody. Competition inhibition test, indirect ELISA test, and immune
      flow cytometry were used for analyzing the serum characterization of anti-anti
      idiotypic antibody (Ab3) and the changes of T lymphocyte phenotype of spleen.
      RESULTS: The specific antitumor immune response could be induced in BALB/c mice
      after immunized with anti-idiotypic minibody without carrier proteins and
      adjuvant. The Ab3 maintained at a high level till 30 day after the last
      immunization. It stimulated proliferation of CD4+ T cells and CD8+ T cells from
      the spleen of BALB/c mice on 4th day, 14th day, 24th day, and 30th day after the
      last immunity respectively. CONCLUSIONS: 6B11 anti-idiotypic minibody can induce
      both humoral and cellular immunity against ovarian carcinoma in vivo, which
      provided experimental evidence for clinical use of fusion protein 6B11 minibody
      as anti-idiotype vaccines against ovarian carcinoma.

PMID- 15248912
TI  - [Expression of Epstein-Barr virus genes in EBV-associated gastric carcinoma].
AB  - BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) is associated with the
      development of many malignant tumors. The forms of EBV and the expression of EBV
      genes in Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) have been
      reported. These studies showed that the forms of EBV and the expression of EBV
      genes are various in different types of malignancies. However, there were only a
      few reports about the expression of EBV genes, especially the lytic genes, in
      gastric carcinoma tissues. This study was to determine the expression of EBV
      latent and lytic infection genes in gastric carcinoma at the transcriptional
      level by RT-PCR and Southern hybridization,and investigate the relationship
      between EBV-encoded genes and the tumorigenesis of gastric carcinoma at the
      molecular level. METHODS: One hundred and eighty-five gastric carcinoma and
      corresponding para-carcinoma tissues were tested for EBV genome by polymerase
      chain reaction (PCR)-Southern analysis. EBV-encoded small RNA 1 (EBER1) of the
      PCR positive specimens was determined by in situ hybridization (ISH). Gastric
      carcinoma with positive EBER1 signals was confirmed EBV- associated gastric
      carcinoma (EBVaGC). RT-PCR and Southern hybridization were used to determine the
      expression of nuclear antigen (EBNA) promoters (Qp, Wp and Cp), EBNA 1 and
      2,latent membrane protein (LMP) 1, 2A, and 2B and lytic genes (immediate-early
      genes BZLF1 and BRLF1, early genes BARF1 and BHRF1, late genes BcLF1 and BLLF1)
      in EBVaGCs. RESULTS: There were 13 EBV positive samples in gastric carcinomas
      (7.03%), but no EBV positive sample in corresponding para-carcinomas. The
      transcripts of Qp were detected in all of the 13 EBVaGCs tissues, while both Wp
      and Cp were silent. All of the 13 cases expressed EBNA1 mRNA, but no EBNA2, LMP1,
      and LMP2B mRNA. LMP2A mRNA was detected in 5 of the 13 cases. Of the 13 EBVaGCs,
      7 exhibited BcLF1 transcript and 2 exhibited BHRF1 transcript. The transcripts of
      BZLF1 were detected in 6 cases, and those of BARF1 also in 6 cases. No BLLF1 and
      BRLF mRNA were detected in the 13 EBVaGCs. CONCLUSIONS: The latent pattern of EBV
      in EBVaGCs corresponds to the latency I or unique latency I/II, intermediate
      between the latency I and II. Part of lytic infection genes are expressed in
      EBVaGCs tissues. BARF1 and BHRF1 genes express in part of gastric carcinomas and
      their roles in gastric tumorigenesis need to be further studied.

PMID- 15248913
TI  - [HSV-TK gene therapy of lung adenocarcinoma xenografts using a hypoxia/radiation
      dual-sensitive promoter].
AB  - BACKGROUND & OBJECTIVE: Radio-genetic therapy is a novel strategy for cancer
      treatment; however, a limited success was shown due to lower sensitivity of tumor
      cells to radiation under hypoxia, which is a unique feature for solid tumors. In
      order to improve the efficacy of radiogenetic therapy for lung cancer, a
      hypoxia/radiation dual-sensitive promoter was constructed to enhance the
      expression of HSV-TK in transfected cells exposed to radiation under hypoxia.
      METHODS: The chimeric promoter HRE-Egr was generated by insertion of hypoxia
      response elements (HREs) upstream of the Egr-1 (early growth response gene-1)
      promoter. HSV-TK expression vector was constructed by cloning HRE-Egr promoter
      upstream of HSV-TK gene, which was transfected into A549 cells via liposome. The
      expression of HSV-TK in transfected cells exposed to irradiation (6 Gy) and/or
      hypoxia (1% O2) were analyzed by Northern blot, and the relative survival rate of
      cells in presence of prodrug ganciclovir (GCV) was tested using MTT method. To
      examine the efficacy of this HRE-Egr-TK gene therapy in vivo, the A549
      adenocarcinoma xenografts were planted in BALB/c nude mice. The tumor volumes and
      the suppression rates were assayed in nude mice bearing xenografts infected with
      plasmids and exposed to radiation. RESULTS: HSV-TK gene expression in transfected
      cells was markedly increased in both radiation (227 U) and hypoxia (94 U) groups
      compared with control group (21 U). The HSV-TK expression (769 U) in transfected
      cells exposed to radiation under hypoxia is much more higher than the former
      groups. The survival rate of transfected cells exposed to radiation under hypoxia
      in the presence of GCV was obviously decreased with comparison of cells under
      normoxia (7.2%+/-1.8 % vs 32.7%+/-4.6 %). HRE-Egr promoter transfected tumors
      regressed significantly after a combination therapy of irradiation and GCV in all
      mice (n=10), the tumor suppression rates was 91.2%. CONCLUSIONS: The
      hypoxia/radiation dual-sensitive promoter HRE-Egr can enhance the HSV-TK gene
      expression in solid tumors under hypoxia. Enhanced tumor suppression effect was
      observed in A549 xenografts infected with HRE-Egr promoter exposed to radiation.

PMID- 15248914
TI  - [Diagnosis of lymph node micrometastases in human lung carcinoma: determination
      of p53 gene mutations by polymerase chain reaction-temperature gradient gel
      electrophoresis (PCR-TGGE)].
AB  - BACKGROUND & OBJECTIVE: Metastasis is one of the most important factors in
      determining the prognosis of lung cancer patients. However, it is difficult to
      determine single cancer cell in lymph nodes by routine methods. This study was
      designed to investigate a sensitive method for detecting lymph node
      micrometastases in human lung carcinomas. METHODS: Mutation detection for p53
      gene (exon 5-8) was performed in 39 cases of primary lung carcinomas and 110
      corresponding lymph nodes (LNS) by PCR-TGGE method. Serial sectioning was
      performed to confirm micrometastases in some of these samples. RESULTS: p53
      mutations were found in 23 of 39 cases with primary lung cancer. Forty LNSs
      showed p53 mutation in 67 corresponding LNSs. They were located at the same exon
      as their primary tumors. Only twenty-six LNSs were detected metastases by routine
      histopathology. Forty-three LNSs from sixteen cases of primary tumor without p53
      mutation and ten LNSs from the patients without tumor disease did not have any
      p53 mutations. By PCR-TGGE assay p53 gene mutations were determined in fourteen
      LNSs without histopathological evidence of metastasis. Micrometastases were found
      in four of the serially sectioned cases. CONCLUSION: Mutation detection for p53
      gene (exon 5-8) showed lymph node micrometastases in patients with lung
      carcinoma. It may be used as a complement for the routine histopathology.

PMID- 15248915
TI  - [Correlation among expression of E-cadherin, beta-catenin, and cyclin D1 in
      breast cancers].
AB  - BACKGROUND & OBJECTIVE: E-cadherin links to the cytoskeleton via catenins and
      mediates cell-cell homophilic adhesion. beta-catenin not only regulates cell-cell
      adhesion as a protein interacting with cadherin, but also functions as an
      important component of the Wnt signaling pathway which has been found to be
      closely associated with tumor formation. This study was performed to examine the
      expression of E-cadherin, beta-catenin, and cyclin D1 in breast cancer in order
      to evaluate their possible roles in the formation and progression of breast
      cancer. METHODS: The alterations of E-cadherin, beta-catenin, and cyclin D1 in 60
      cases of breast cancer were determined using highly sensitive SP
      immunohistochemical method. RESULTS: Normal immunoreactivity of E-cadherin and
      beta-catenin were observed in 29 (48.3%) and 18 (30.0%) cases, respectively.
      Twenty-eight cases (46.7%) showed cyclin D1 overexpression. Thirty percent (9/29)
      of the cases with normal staining of E-cadherin showed overexpression of cyclin
      D1, while 61.3%(19/31) of the cases showed overexpression of cyclin D1 with
      abnormal staining of E-cadherin. Abnormal expression of E-cadherin and
      overexpression of cyclin D1 showed a significantly positive correlation
      (rs=0.303,P< 0.05). Forty-two cases showed abnormal staining of beta-catenin.
      Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases with
      abnormal staining of beta-catenin, but only observed in 22.2% (4/18) of these
      cases with normal membranous staining of beta-catenin. There was a significantly
      positive correlation between the abnormal expression of beta-catenin and
      overexpression of cyclin D1 (rs=0.321, P< 0.05). CONCLUSION: Down-regulation of E
      cadherin and beta-catenin accumulation in the cytoplasm/nuclear may promote
      malignant transformation and progression by triggering cyclin D1 overexpression
      in breast cancer.

PMID- 15248916
TI  - [p53-dependent antiproliferation and apoptosis of H22 cell induced by melatonin].
AB  - BACKGROUND & OBJECTIVE: It has been shown that melatonin has a direct inhibitory
      effect on the proliferation of H22 mouse hepatoma cells in our research. This
      study was designed to investigate its molecular mechanism. METHODS: (1) Animal
      models were established by transplanting H22 cells and treated with melatonin,
      and then the p53 and cyclin E of the tumor tissue were determined by
      immunohistochemical analysis. (2) After treatment of H22 cells with melatonin in
      vitro, the percentage of cells in each cell cycle phase and apoptosis rate were
      analyzed by flow cytometry. p53 and cyclin E were determined again by
      immunohistochemical analysis. The level of Fas mRNA was examined by real time
      polymerase chain reaction (RT-PCR). RESULTS: (1) After treated with melatonin (1
      x 10(-6) mol/L), the number of the H22 cells in phase G(0)/G(1) were elevated
      from 75.24% to 85.46%, while which in phase S almost decreased from 10.32% to 0,
      and at the same time, the number of apoptotic cells increased from 5.07% to
      12.77%. (2) Compared with the control, the level of p53 elevated 42.5% (in vitro)
      and 19.5% (in vivo), however, the level of cyclin E decreased 31.7% (in vitro)
      and 39.9% (in vivo). (3) Fas mRNA increased about 44.2% after melatonin treatment
      (P< 0.01). CONCLUSION: Melatonin inhibits the proliferation of H22 cells by
      arrest and apoptosis, and the mechanism perhaps interferes with increasing p53
      that results in down-regulation of cyclin E indirectly and stimulates the
      expression of Fas gene.

PMID- 15248917
TI  - [Experimental study of bio-distribution and tumor imaging of 131I in nude mice
      bearing human breast cancer].
AB  - BACKGROUND & OBJECTIVE: Previous study showed that about 85% of local and
      metastatic tissues of the estrogen-receptor-positive breast cancer express a
      large number of sodium/iodide symporter (NIS), which transfers the iodide from
      blood into cancer cells, leading to much higher cellular concentration in breast
      cancer than normal tissues. This study was designed to investigate the specific
      affinity of (131)I to the estrogen-receptor-positive breast cancer cells through
      the biodistribution and tumor imaging of the nude mice bearing breast cancer.
      METHODS: MCF-7/ER(+) and MCF-7/ER(-) nude mice bearing human breast cancer were
      prepared for the experiments. The animals were intraperitoneally injected with 37
      55.5 MBq (131)I when the tumor grew to 0.8-1.0 cm. The tissue distribution of
      (131)I was determined at 6, 12, and 24 h after injection. The percentage of
      absorbed (131)I per gram of tissue (%ID/g) and the ratio of (131)I in tumor and
      non-tumor tissues (T/NT) were calculated. Meanwhile, the nude mice were imaged at
      different time. RESULTS: The (131)I was mainly concentrated in tumor, thyroid,
      blood, liver, stomach, and kidney at 6 h, and the concentration of (131)I in
      tumor of MCF-7/ER(+) group was significantly higher than that of MCF-7/ER(-)
      group at 6 h. At 12 h, the T/NT ratio of blood, heart, lung, intestine, and
      muscle were 2.39, 3.06, 3.94, 7.69, and 7.60, respectively, and increased to
      5.15, 5.47, 5.29, 11.44, and 10.99 at 24 h. The T/NT ratio of MCF-7/ER(-) group
      was significantly lower than that of MCF-7/ER(+) group (P< 0.05). The imaging
      results showed that there was localized radioactivity in tumor tissue in the MCF
      7/ER(+) group mice at 12 h, while no in MCF-7/ER(-) group mice. CONCLUSION:
      (131)I could be concentrated particularly in the estrogen-receptor-positive nude
      mice bearing breast cancer tissue.

PMID- 15248918
TI  - [Polymorphism analysis of 5' promotor region of BCR gene].
AB  - BACKGROUND & OBJECTIVE: BCR-ABL fusion gene is regarded as the molecular hallmark
      of chronic myelogenous leukemia (CML), and its expression is controlled by the
      BCR gene promoter. This study was designed to investigate the polymorphism of the
      promoter region of BCR gene, and its possible correlation with the disease.
      METHODS: A 1.13 kb fragment of BCR gene 5' promotor region was amplified and
      sequenced from 30 CML patients and 19 controls. Transcription factor binding
      sites and repeat sequences in this region were analyzed using softwares and
      online tools. RESULTS: Four novel single nucleotide polymorphisms (SNPs) and 3
      bases different from the reference sequence were detected in the region studied.
      Among these 2 novel SNPs and 1 different base were located in or near several
      bases of binding sites. The gene frequencies of the novel SNPs had no significant
      difference between CML and control people. CONCLUSION: Sequence polymorphisms
      were found in the 5' promotor region of BCR gene, most of them being SNPs. No
      relativity can be validated between the SNPs and the disease. But it appears that
      some SNPs might have the probability of bringing influence to the transcription
      and expression of the gene.

PMID- 15248919
TI  - [Inhibitory effect of MUC2 antisense oligodeoxynucleotide with lipofectin on
      human gastric cancer cell proliferation].
AB  - BACKGROUND & OBJECTIVE: Our previous study showed that the expression of MUC2
      protein was related with the biological behavior of gastric carcinoma. The aim of
      the present study was to investigate the inhibitory effect in vitro of mucin gene
      MUC2 antisense oligodeoxynucleotide (ASODN) on its gene expression and cell
      proliferation on gastric cancer cells SGC7901. METHODS: Phosphorothioate MUC2
      ASODN was synthesized and transfected to SGC7901 cells mediated by lipofectin.
      Its inhibitory effects on cell proliferation was determined by MTT method, light
      and electron microscopy and immunohistochemical method. RESULTS: The
      determination by MTT method demonstrated that MUC2 ASODN of varied concentration
      significantly inhibited the growth of SGC7901 cells while the control lipofectin
      and control N-ODN showed no such effect. The inhibitory effect was dose-dependent
      and time-dependent. The inhibition peaked at 48th hour after transfection, and
      the inhibition rate reached 55% when the MUC2 ASODN concentration was 0.5
      micromol/L. After transfecting with MUC2 ASODN, SGC7901 cells showed decrease in
      number, volume, and karyokinesis, and increase in necroses under light
      microscopy. Mitochondrion swelling, increased liposomes, myelin figures,
      chromatin margination were found under electron microscopy. And the test by
      immunohistochemical method indicated that transfected MUC2 ASODN downregulated
      the expression levels of MUC2 protein, but upregulated the expression levels of
      p16 protein. CONCLUSION: MUC2 ASODN transfection could specifically inhibit
      SGC7901 cells proliferation.

PMID- 15248920
TI  - [Long-term prognosis after hepatic resection for huge primary liver cancer].
AB  - BACKGROUND & OBJECTIVE: Primary liver cancer (PLC) larger than 10 cm in diameter
      is called huge PLC. Huge PLC accounts for a number of patients at the time of
      diagnosis in clinical practice. The outcome of resection in these patients has
      not been clearly demonstrated. This study was to evaluate the outcome and
      determined the prognostic factors affecting long-term survival following
      hepatectomy for huge PLC. METHODS: One hundred and seventy-three patients with
      huge PLC who underwent hepatectomy from 1964 to 1993 were followed up to January
      2003 and reviewed retrospectively. The factors affecting long-term survival were
      studied by univariate and multivariate analysis. RESULTS: The overall 3-, 5-, and
      10-year survival rates were 31.9%, 21.8%, and 8.3%, respectively. Thirty-seven
      patients survived more than 5 years and 8 patients survived more than 10 years.
      Univariate analysis showed that sex, Child-Pugh classification, degree of
      coexisting cirrhosis and radical resection were significant prognostic factors.
      The Cox multivariate proportional hazard model indicated that independent
      prognostic factors for long-term survival were degree of coexisting cirrhosis and
      radical resection. CONCLUSIONS: Hepatic resection for huge PLC offers the chance
      of long-term survival. It should be used to treat patients with huge PLC at first
      choice. Degree of coexisting cirrhosis and radical resection were the only two
      prognostic factors for long-term survival following hepatectomy for huge PLC.

PMID- 15248921
TI  - [Efficacy of 3-dimensional conformal hypofractionated single high-dose
      radiotherapy combined with transcatheter arterial chemoembolization for portal
      vein tumor thrombus in patients with hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Hepatocellular carcinoma (HCC) often results in portal
      vein tumor thrombus (PVTT), and the prognosis of the patients is extremely poor.
      It has been reported that some oversea scholars achieved fine therapeutic effects
      in treatment of this disease by 3-dimensional conformal radiation therapy (3DCRT)
      in fractionated conventional dose. The aim of this study was to evaluate the
      efficacy of 3-dimensional conformal hypofractionated single high-dose
      radiotherapy combined with transcatheter arterial chemoembolization (TACE) for
      portal vein tumor thrombus in patients with hepatocellular carcinoma. METHODS:
      From May 1998 to December 2000, 35 patients with unresectable HCC complicated
      with PVTT were treated with 3-dimensional conformal hypofractionated single high
      dose radiotherapy and TACE. According to the volume of the tumors, radiotherapy
      was performed at an exposure of 4-8 Gy/time, 3 times/week, 48-60 Gy, 8-12 times,
      3.0-3.5 weeks. The objective responses were analyzed and the survival rates were
      assessed from the date of the beginning of treatment using the Kaplan-Meier
      method. The Cox proportional hazards model was used to analyze the prognostic
      factors. RESULTS: The objective response was 71.4%. The overall survival rates
      were 59.3%, 31.6%, and 26.6% at 1, 2, 3 years, respectively, with a median
      survival time of 11 months. Cox proportional hazards model analysis showed that
      Child-Pugh class was the most important prognostic factors for the survival
      probability of the patients. Radiation-induced liver disease (RILD) and
      gastrointestinal bleeding were the most common treatment-related complications.
      CONCLUSIONS: 3-Dimensional conformal hypofractionated single high-dose
      radiotherapy combined with TACE is an effective and feasible approach to treat
      PVTT in unresectabe HCC patients. Child-Pugh class was identified as a predictor
      for PVTT in unresectabe HCC patients.

PMID- 15248922
TI  - [Long-term result of combination of transcatheter arterial chemoembolization and
      percutaneous ethanol injection for treatment of hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Both transcatheter arterial chemoembolization (TACE) and
      percutaneous ethanol injection (PEI) are the most important and popular
      procedures of interventional treatment for hepatocellular carcinoma (HCC).
      Although the improvement of the short-term efficacy of the combination of TACE
      and PEI has been proved, the long-term efficacy is seldom reported so far. The
      purpose of this study was to evaluate the long-term efficacy of the combination
      of TACE and PEI for treatment of HCC. METHODS: Six hundred and seventy-five
      patients with HCC from 2 cm to 15 cm in the greatest diameter (average 9.6 cm)
      were enrolled in this study. Among them, 179 were treated by a combination of
      TACE using the emulsion of lipiodol and anti-cancer drugs and PEI (TACE/PEI
      group) and 496 patients by TACE alone (TACE group). Ten patients in each group
      underwent resection after the final interventional treatment and the resected
      specimens were detected by histopathology method. The unresected patients had
      been followed up for 5-7 years and the 1-, 3-, 5 -, and 7-year survival rates
      were evaluated. The clinical data of the patients in two groups before
      intervention were comparable. RESULTS: Pathological data of two groups showed
      that remarkable differences were found in the mean necrosis rates (100.0+/-0.0%
      vs 91.5+/-7.1%, P< 0.05) and the complete necrosis rates of tumors (100% vs 20%,
      P = 0.0007), while there were no statistical significances in the extent of
      shrinkage of tumors after treatment between two groups. The results of follow-up
      showed that the 1-, 3-, 5-, and 7-year survival rates were 80.5%, 58.6%, 29.6%,
      16.5% in TACE-PEI group, and 68.5%, 27.8%, 7.2%, 5.2% in TACE group,
      respectively. Significant differences were found between two groups (P< 0.01).
      CONCLUSION: The combination of TACE and PEI is a valuable remedy for HCC to
      prolong long-term survival rate.

PMID- 15248923
TI  - [Multidetector spiral CT findings of arteriovenous fistula associated with
      hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: In clinical practice, a large number of patients might
      not undergo transcatheter hepatic angiography as a routine examination, which
      resulted in missed diagnosis of arteriovenous fistula (AVF) associated with
      hepatocellular carcinoma (HCC) and loss of embolism opportunity. The study was
      designed to investigate multidetector spiral CT (MDSCT) findings of AVF
      associated with HCC, so as to improve its diagnosis and differential diagnosis.
      METHODS: Thin-slice and dynamic enhancement MDSCT findings of AVF proved by
      digital subtraction angiography of 56 patients with HCC were analyzed. RESULTS:
      MDSCT demonstrated earlier enhancement of main portal trunks and/or the first
      order branches than superior mesenteric veins or spleen veins (n=31), 1 patient
      had early enhancement and strong enhancement of left hepatic vein with thromboses
      in it and upper part of inferior vena cava, 1 patient had transient patchy
      enhancement peripheral to HCC focus in late hepatic arterial phase and became
      isoattenuation at portal vein phase among them; stronger opacification of main
      portal trunks and/or the first order branches than superior mesenteric veins or
      spleen veins (n=18); earlier enhancement of the second order branches and smaller
      of portal veins than main portal trunks (n=4), stronger opacification of the
      second order branches and smaller of portal veins than main portal trunks (n=3),
      accompanying with transient patchy enhancement (n=3) or wedge-shaped enhancement
      (n=4) peripheral to HCC foci at late hepatic arterial phase and became
      isoattenuation at portal vein phase. Enhancement degrees of HCC foci and spleens
      were all decreased, and enhancement degrees of liver parenchyma without HCC foci
      were increased and heterogeneous in 49 patients with severe or moderate and
      central AVF. CONCLUSION: There are complex MDSCT findings of AVF associated with
      HCC, and its main manifestations are earlier enhancement and stronger
      opacification of portal veins and/or hepatic veins.

PMID- 15248924
TI  - [Intravesial instillation of recombination interferon-alpha and pirarubicin in
      the prophylaxis of local recurrence after resection of the superficial bladder
      cancer].
AB  - BACKGROUND & OBJECTIVE: Superficial transitional cell carcinoma (TCC) of urinary
      bladder tends to recur after transurethral surgery. This study was designed to
      evaluate the effect of interferon-alpha (IFN-alpha)and pirarubicin (THP) on
      decreasing postoperative recurrence of superficial bladder cancer. METHODS:
      Recombinant IFN-alpha and THP has been used in clinical study. One week After
      operation, 68 patients were prospectively enrolled and divided into two groups
      randomly: IFN-alpha plus THP group and THP group. The protocols of
      chemoimmunoprophylaxis include 8 weekly and 10 monthly instillation of 3 x 10(7)
      IU IFN-alpha plus 40 mg THP in 40 ml 5% glucose via catheter. RESULTS: The follow
      up period ranged from 6 to 32 months (median 18.2 months). The cytoscopy and
      cytology with cold cup biopsies had been carried out every 3 months for 2 years.
      Recurrence after instillation of IFN-alpha combining THP was observed in only 4
      cases (12.1%), bladder irritation was found in 4 cases, fatigue in 3 cases, and
      rash in 1 case as well. Among the 35 cases in THP group, recurrence was found in
      8 cases (22.8%), bladder irritation in 5 cases, fatigue in 3 cases. IFN-alpha
      plus THP yielded better effect than THP alone (P< 0.05),especially in grade 3 and
      stage PT1 bladder cancer. CONCLUSIONS: IFN-alpha working in coordination with THP
      would be an effective remedy to prevent the recurrence of bladder cancer. The
      intravesical IFN-alpha plus THP appears to be more effective against recurrence
      than THP alone. Further study is needed for side-effect and popularization in
      such way.

PMID- 15248925
TI  - [Clinical evaluation of management of superior mediastinal metastasis from
      thyroid carcinoma with systemic superior mediastinal dissection via sternotomy
      approach: 12 cases report].
AB  - BACKGROUND & OBJECTIVE: Few research of surgery for superior mediastinal
      metastasis from thyroid carcinoma has been reported. Previous surgical approach
      from neck had the problems of easy damage of nerve and vessels and the difficulty
      of clearance of lymph nodes. This study was designed to assess the value of
      systemic superior mediastinal lymph node dissection via sternotomy for superior
      mediastinal metastasis from differentiated thyroid carcinoma. METHOD: A
      retrospective study was performed to analyze the clinical pathologic data as well
      as the outcome of 12 cases of differentiated thyroid carcinoma treated with
      systemic superior mediastinal lymph node dissection via sternotomy approach from
      April 1995 to April 2002, including 7 cases of papillary adenocarcinoma and 5
      cases of medullary carcinoma. RESULTS: Pathologically, the incidence rates of
      metastasis to anteriotracheal lymph node, paratracheal lymph node, anterior
      superior vena cava, and anterior innominate artery lymph nodes were 55.6%
      (25/45), 57.1% (36/63), 42.1% (8/19) and 30% (3/10), respectively. All cases are
      still alive in one to seven years follow-up period. The median follow-up was 32
      months. Upper mediastinal lymph nodes were recurrent in one case; distant
      metastasis occurred in two cases. CONCLUSION: Systemic superior mediastinal lymph
      node dissection via sternotomy approach can be employed in treating superior
      mediastinal lymph node metastasis from differentiated thyroid carcinoma due to
      its safety and relatively satisfactory outcome.

PMID- 15248926
TI  - [Correlation analysis among expression of ERCC-1, metallothionein, p53 and
      platinum resistance and prognosis in advanced non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: The molecular predictor for cisplatin sensitivity in
      advanced non-small cell lung cancer (NSCLC) is still an open question at present.
      The purpose of this study was to evaluate the relationship of the cisplatin
      sensitivity/prognosis with the expression of excision repair cross complement-1
      (ERCC-1), metallothionein (MT), and p53 in the paraffin-embedded tissue of
      advanced non-small cell lung cancer (NSCLC). METHODS: From January 1994 to
      December 2001, 51 pathologically confirmed advanced NSCLC patients were included.
      All patients received cisplatin contained regimen chemotherapy (Gemzar + DDP or
      NVB + DDP) as the first line treatment. At the same time, the tumor samples were
      collected and the expression of ERCC-1, MT, and p53 in the tumor samples were
      examined by immunohistochemical method. The response rates and survival data were
      analyzed according to the over-expression or not of these three parameters
      (negative group/over-expression group). The response rates were compared by
      Chi(2) test. Kaplan-Meier method and Cox proportional hazards model were used for
      survival analysis. RESULTS: In these 51 patients, the expression rates of ERCC-1,
      MT, and p53 were 42.8%, 57.5%, and 37.8%, respectively. The response rates in
      negative group/over-expression group of ERCC-1, MT, and p53 were 33.3%/16.7%,
      35.3%/27.3%, and 21.4%/35.3%, respectively (1.99, 1.29, and 0.61 times,
      respectively, P >0.05). The response rate in both ERCC-1 and MT negative group
      was 37.5%. In both ERCC-1 and MT over-expression (co-expression) group, the
      response rate was 14.3%. The former was 2.6 times of the latter (P >0.05). The
      average survival time in negative group/over-expression groups were 621/523 days
      (for ERCC-1), 556/479 days (for MT), 599/416 days (for p53), respectively. ERCC
      1, MT, or p53 over-expression group showed poorer prognosis than those of
      negative group by Kaplan-Meier analysis. But in multivariate analysis, only p53
      over-expression was an independent poor prognostic factor of survival time (Cox
      regression, P=0.009). CONCLUSION: Whether over-expression of ERCC-1 and MT can be
      used as a molecular marker of cisplatin resistance in advanced NSCLC patients
      need further study. Over-expression of p53 predicates poor prognosis for patients
      with advanced NSCLC.

PMID- 15248927
TI  - [Expression of estrogen receptor and progesterone receptor in colorectal cancer:
      a quantitative study].
AB  - BACKGROUND & OBJECTIVE: It was indicated that there was relationship between
      estrogen and colorectal cancer. Estrogen receptor (ER) and progesterone receptor
      (PR) were expressed in colorectal cancer tissue. They were measured using
      immunohistochemistry with various results,but there was little quantitative
      study. This study was designed to quantitatively measure the expression of ER and
      PR in tumor tissues and normal mucosas and analyze its relationship with
      clinicopathological parameters in colorectal cancer. METHODS: ER and PR
      expression in cytoplasm and nucleus of tumor tissues and normal mucosas from 45
      colorectal cancer patients were quantitatively measured using radioligand binding
      assay (RBA). RESULTS: ER and PR were expressed in all tumor tissues and normal
      mucosas. In cytoplasm, the ER expression level of tumor tissues was higher than
      that of normal mucosas; they were 7.96+/-3.69 fmol/mg protein and 4.34+/-2.84
      fmol/mg protein (P< 0.01) respectively. And that was the same for PR expression;
      they were 3.89+/-2.64 fmol/mg protein and 2.50+/-1.73 fmol/mg protein(P<
      0.01)respectively. In nucleus, the ER expression level of tumor tissues was
      higher than that of normal mucosas; they were 18.42+/-8.30 fmol/mg protein and
      11.24+/-5.44 fmol/mg protein (P< 0.01)respectively. And that was the same for PR
      expression, they were 9.36+/-5.90 fmol/mg protein and 7.84+/-7.41 fmol/mg protein
      (P< 0.05) respectively. There was positive correlation between ER and PR
      expression in cytoplasm and nucleus of tumor tissues (P< 0.01) respectively,so
      was in cytoplasm in normal mucosas (P< 0.01) respectively, but not in nucleus (P
      >0.05). There was correlation between ER expression in tumor tissues and
      patients' age,and the expression in these people over 45 years old was higher
      than those less 45 years old (P< 0.05), but no correlation between tumor tissues
      PR expression and age (P >0.05). There was no correlation between tumor tissues
      ER, PR expression and sex, staging, tumor location, size, gross and histological
      type, invasive depth, lymph nodes metastasis, or tumor tissue CEA expression (P
      >0.05). CONCLUSIONS: ER and PR expression in colorectal tumor tissues were higher
      than those in normal mucosas, and there was positive correlation between ER and
      PR expression in tumor tissues. All these indicate that ER in colorectal cancer
      tissues has some activity. The level of the ER, PR expression in tumor tissue
      could not predict the malignant biological behaviors of colorectal cancer.

PMID- 15248928
TI  - [Clinicopathological significance of homeobox gene BP1 mRNA expression in human
      breast cancer].
AB  - BACKGROUND & OBJECTIVE: Beta protein 1 (BP1) gene, a novel member of DLX homeobox
      gene family, is located in 17q21-22 region and overexpressed in both acute
      myeloid leukemia and acute T cell lymphocytic leukemia. However, the reports on
      the function of BP1 in solid tumors are rare. The study was designed to determine
      the expression of BP1 gene in breast cancer and to analyze its relationship with
      various clinicopathological factors. METHODS: With beta-actin gene as a
      reference, BP1 mRNA expression was detected in 82 breast cancer tissues and 12
      near adjacent tissues and 10 far adjacent tissues using reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The expression rates of BP1 in near
      and far adjacent tissues were 16.67% (2/12) and 0% (0/10), respectively; while
      the expression rate in breast cancer group was 64.63% (53/82). There were
      statistically significant differences among the three groups (P< 0.05).
      Overexpression of BP1 in breast cancer was correlated with histological grade (P<
      0.05). Nevertheless, no correlation was found between BP1 expression and other
      clinicopathological factors, including tumor size, lymph nodal metastasis, family
      history, pathological type, menarcheal age, primiparous age, number of pregnancy,
      menopausal status, ER status and PR status (P >0.05). CONCLUSION: BP1 gene is of
      upregulated expression in breast tumors and could be regarded as a new and vital
      biomarker in breast cancer research.

PMID- 15248929
TI  - [New developments in application of laser capture microdissection].
AB  - Isolation of pure targeted cells is an important and essential step for the
      molecular analysis of tissue lesion occurred in the progression of disease. Laser
      capture microdissection (LCM) is a novel technique that can be applied to obtain
      pure targeted cell subgroup or even a single cell quickly and precisely under the
      microscope, thus the problem of tissue heterogeneity in molecular analysis can be
      tackled successfully. In this article, the principles, advantages and
      disadvantages of LCM were introduced. New developments in the application of LCM
      were summarized in two fields (DNA analysis and gene expression analysis)
      respectively. Meanwhile, possible directions of the future developments of LCM
      were put forward.

PMID- 15248930
TI  - Compassion in life, caring in death: a view from the other side.

PMID- 15248931
TI  - Quality of life evaluations of caregivers of ovarian cancer patients during
      chemotherapy treatment.
AB  - OBJECTIVES: (1) To examine the quality of life (QOL) of caregivers of women
      undergoing chemotherapy for advanced ovarian cancers, and (2) to correlate the
      QOL measures of caregivers to those of the women undergoing chemotherapy.
      METHODS: Over a 9-month period, all women undergoing chemotherapy for ovarian
      cancer at the Saskatoon Cancer Centre, and their caregivers, were offered
      participation. Two well-validated instruments were used to measure the "quality
      of life" concept. Women with ovarian cancer completed the Functional Assessment
      of Cancer Therapy--Ovarian (FACT-O) questionnaire in the clinic prior to each
      course of chemotherapy. Each caregiver completed a Caregiver Quality of Life
      Index--Cancer (CQOL-C) questionnaire at home at the start and conclusion of each
      chemotherapy regimen (cycle 1 and after the last chemotherapy treatment). The
      demographics of the caregivers were described. A paired t test was used to detect
      changes to caregivers' QOL scores before and after chemotherapy treatment.
      Correlation analysis was carried out to examine the relationship between the
      caregivers' total QOL scores and the various subscale and total scores of the
      FACT-O questionnaires completed by the women with ovarian cancer. Multivariate
      regression models were constructed to examine the relative importance of each of
      the QOL domain measures of the woman with cancer in predicting the effect on her
      caregiver's QOL. RESULTS: Thirty different patient-caregiver pairs participated
      in the study, providing 50 separate assessments since not all pairs had completed
      the post-chemotherapy assessments. There was improvement (P <.05) in the
      caregiver's QOL scores at the conclusion of the chemotherapy treatment compared
      to the baseline assessments. The improvement was unrelated to the performance
      status or response to chemotherapy of the woman undergoing treatment. There was
      also a correlation (P <.05) between an increase in a caregiver's distress and
      worsening scores in the "emotional," "functional," and "concerns" QOL domain
      assessments of the woman undergoing treatment. Stepwise regression analysis
      showed the "concerns" score, measuring specific ovarian cancer-related symptoms,
      to be the only predictor of a caregiver's distress (P <.05). CONCLUSIONS:
      Standard chemotherapy for ovarian cancer does not worsen a caregiver's QOL. There
      is a direct relationship between the QOL of women with cancer and that of their
      caregivers. Future research is required to identify how best to integrate the
      results of QOL assessments in cancer treatment protocols and to examine the long
      term effects of ovarian cancer and its treatment on both caregivers and the women
      for whom they care.

PMID- 15248932
TI  - Single room maternity care: perinatal outcomes, economic costs,and physician
      preferences.
AB  - OBJECTIVES: (1) To compare perinatal outcomes and costs of care among women
      giving birth in a single room maternity care (SRMC) setting versus a traditional
      delivery suite or postpartum setting; and (2) to report on physicians' responses
      to the SRMC environment. METHODS: Among women who were determined to be at "low
      risk" for intrapartum complications through the use of a triage tool, the
      outcomes of those receiving care in the new SRMC unit were compared to the
      outcomes of those cared for in the traditional delivery suite and postpartum
      modules. Total costs of the entire maternity service before and after
      implementation of SRMC were also compared. Physicians were surveyed about the
      adequacy of the physical environment. RESULTS: Rates of intrapartum interventions
      and adverse outcomes were similar in both groups, with the exception of less
      frequent electronic fetal monitoring in the SRMC setting. Caesarean section rates
      were lower than expected in both groups. Length of stay was significantly shorter
      in the SRMC group (55.1 +/- 26.5 days vs. 61.0 +/- 24.3 days; <.001). Staff
      positions in the hospital were reduced from 206 to 193.7. Direct costs for women
      of similar acuity (resource intensity weightings) were reduced by 24% (1809
      dollars vs. 2377 dollars). The proportion of physicians preferring SRMC to the
      traditional setting increased from 45.8% at 6 months to 78.7% at 12 months after
      implementation of the SRMC model (P =.003). CONCLUSION: SRMC is a model of
      obstetric care for women at low risk for intrapartum complications, offering cost
      savings without affecting perinatal outcomes, and is well accepted by physicians.

PMID- 15248933
TI  - The effect of family physician timing of maternal admission on procedures in
      labour and maternal and infant morbidity.
AB  - OBJECTIVE: To determine if a family physician practice pattern of early admission
      is associated with increased rates of intervention in labour and delivery, and/or
      adverse maternal and newborn outcomes. METHOD: A retrospective cohort study
      compared women under the care of family physicians having 50% or more of their
      patients admitted to the labour and delivery unit "early" (defined as a cervical
      dilatation of < or =3 cm) to women under the care of family physicians having
      less than 50% of their patients admitted "early." Outcome measures included
      labour intervention rates and maternal and neonatal morbidity. RESULTS: After
      adjusting for maternal characteristics, care by family physicians with a practice
      of early admission was associated with increased rates of electronic fetal
      monitoring (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.27-1.89),
      epidural analgesia (OR, 1.34; 95% CI, 1.15-1.55), and Caesarean section (OR,
      1.33; 95% CI, 1.00-1.65) compared to family physicians with a practice pattern of
      late admission. Malposition in labour was associated with more interventions in
      labour than was family physician practice pattern. CONCLUSION: Women under the
      care of family physicians with a practice pattern of early admission were more
      likely to receive electronic fetal monitoring, epidural analgesia, and Caesarean
      section than women under the care of family physicians with a practice pattern of
      late admission. Malposition in labour had a greater effect on procedure use than
      any other variable in our model.

PMID- 15248934
TI  - The 2002 Canadian Contraception Study: Part 2.
AB  - The 2002 Canadian Contraception Study investigated the contraception and sexual
      health-related knowledge, attitudes, and practices of a representative sample of
      Canadian women of childbearing age. In Part 2 of the report of this research, the
      authors focus on the contraceptive attitudes and practices of adolescent women
      and women in their later reproductive years, provide data on sexual and
      reproductive health indicators of Canadian women, describe 2-decade trends in the
      awareness, opinion, and utilization of contraceptive methods among Canadian
      women, and describe contraception counselling strategies that may be used to
      improve patient choice and adherence to method. This report closes with an
      overall discussion of the findings of the 2002 Canadian Contraception Study.

PMID- 15248935
TI  - Vesicouterine fistula in pregnancy: a case report.
AB  - BACKGROUND: Vesicouterine fistula is a rare complication of Caesarean delivery.
      This is the third known report of vesicouterine fistula diagnosed during
      pregnancy. CASE: Linda (pseudonym), a 28-year-old woman in her second pregnancy,
      having had a Caesarean delivery in her first pregnancy, was admitted to the
      delivery unit with possible preterm ruptured membranes at 23 weeks' gestation.
      She also complained of a fluid-filled sac bulging from her introitus during her
      admission assessment. Diagnosis of premature rupture of membranes was confirmed
      by a positive nitrazine paper test and appearance of ferning during microscopic
      evaluation of vaginal fluid. Cystoscopy, performed 3 days after admission,
      demonstrated ballooning of amnion into the bladder. At 24 weeks' gestation, the
      woman had a precipitous vaginal breech delivery. Two months later, the fistula
      was successfully repaired through a transabdominal route. CONCLUSION: Although
      uncommon in pregnancy, vesicouterine fistula should be considered in women who
      present with urinary incontinence or recurrent urinary tract infections after a
      lower transverse Caesarean section. Evaluation in pregnancy is usually limited to
      cystoscopy. Treatment is usually surgical and is often delayed until 2 to 3
      months following delivery.

PMID- 15248936
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 1995 to February 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 after Caesarean with appropriate
      discussion of maternal and 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 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, the woman should deliver in a
      hospital where an immediate Caesarean section is available. The woman and her
      health-care provider must be aware of the hospital resources and the availability
      of obstetric, anaesthesia, 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 immediate Caesarean.
      (III B) 5. Continuous electronic fetal monitoring of women attempting a TOL after
      Caesarean is recommended. (II-2A) 6. Suspected uterine rupture requires urgent
      attention and expedited laparotomy in order to attempt to decrease maternal and
      perinatal morbidity and mortality. (II-2A) 7. Oxytocin augmentation is not
      contraindicated in women undergoing a TOL after Caesarean. (II-2A) 8. 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)9. 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 after appropriate counselling. (II-2B) 10.
      Prostaglandin E1 (misoprostol) is associated with a high risk of uterine rupture
      and should not be used as part of a TOL after Caesarean. (II-2A) 11. A foley
      catheter may be used safely to ripen the cervix in a woman planning a TOL after
      Caesarean. (II-2A) 12. The available data suggest that a trial of labour in women
      with more than one previous Caesarean section is likely to be successful but is
      associated with a higher risk of uterine rupture. (II-2B) 13. Multiple gestation
      is not a contraindication to a TOL after Caesarean. (II-2B) 14. Diabetes mellitus
      is not a contraindication to TOL after Caesarean. (II-2B) 15. Suspected fetal
      macrosomia is not a contraindication to a TOL after Caesarean. (II-2B) 16. 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) 17. Postdatism is
      not a contraindication to a TOL after Caesarean. (II-2B) 18. 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 previous delivery is helpful in
      determining the likelihood of a low transverse incision. If the likelihood of a
      lower transverse incision is high, TOL after Caesarean 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- 15248937
TI  - A pilot study on the use of decision theory and value of information analysis as
      part of the NHS Health Technology Assessment programme.
AB  - OBJECTIVES: To demonstrate the benefits of using appropriate decision-analytic
      methods and value of information analysis (DA-VOI). Also to establish the
      feasibility and implications of applying these methods to inform the
      prioritisation process of the NHS Health Technology Assessment (HTA) programme,
      and possibly extending their use therein. DATA SOURCES: Three research topics
      that were considered by the HTA panels in the September 2002 and February 2003
      prioritisation rounds. REVIEW METHODS: A brief and non-technical overview of DA
      VOI methods was circulated to the panels and Prioritisation Strategy Group (PSG).
      For each case study the results were presented to the panels and the PSG in the
      form of brief case-study reports. Feedback on the DA-VOI analysis and its
      presentation was obtained in the form of completed questionnaires from panel
      members, and reports from panel senior lecturers and PSG members. RESULTS:
      Although none of the research topics identified met all of the original selection
      criteria for inclusion as case studies in the pilot, it was possible to construct
      appropriate decision-analytic models and conduct probabilistic analysis for each
      topic. In each case, the tasks were completed within the time-frame required by
      the existing HTA research prioritisation process. The brief case-study reports
      provided a description of the decision problem, a summary of the current evidence
      base and a characterisation of decision uncertainty in the form of cost
      effectiveness acceptability curves. Estimates of value of information for the
      decision problem were presented for relevant patient groups and clinical
      settings, as well as the value of information associated with particular model
      inputs. The implications for the value of research in each of the areas were
      presented in general terms. Details were also provided on what the analysis
      suggested regarding the design of any future research in terms of features such
      as the relevant patient groups and comparators, and whether experimental design
      was likely to be required. CONCLUSIONS: The pilot study showed that, even with
      very short timelines, it is possible to undertake DA-VOI that can feed into the
      priority-setting process that has been developed for the HTA programme. There are
      however a number of areas that need to be established at the beginning of the
      process, such as clarification of the nature of the decision problem for which
      additional research is being considered, explicitness about which existing data
      should be used and how data that exhibit particular weaknesses should be down
      weighted in the analysis. Other areas, including optimum application of
      researcher time, integrating the vignette (a summary of the clinical problem and
      existing evidence) and the use of DA-VOI, training, use of sensitivity analyses,
      and deployment of clinical expertise, are also considered in terms of the
      potential implementation of DA-VOI within the HTA programme. Recommendations for
      further research include how literature searching should focus on those variables
      to which the model's results are most sensitive and with the highest expected
      value of perfect information; methods of evidence synthesis (multiple parameter
      synthesis) to consider the evidence surrounding multiple comparators and networks
      of evidence; and ways in which the value of sample information can be used by the
      NHS HTA programme and other research funders to decide on the most efficient
      design of new evaluative research. There is also a need for an analytical
      framework to be developed that can jointly address the question of whether
      additional resources would better be devoted to additional research or
      interventions to change clinical practice.

PMID- 15248938
TI  - Systematic review of the effectiveness and cost-effectiveness, and economic
      evaluation, of myocardial perfusion scintigraphy for the diagnosis and management
      of angina and myocardial infarction.
AB  - OBJECTIVES: To assess the effectiveness and cost-effectiveness of single photon
      emission computed tomography (SPECT) myocardial perfusion scintigraphy for the
      diagnosis and management of angina and myocardial infarction (MI). DATA SOURCES:
      Major electronic databases. REVIEW METHODS: Two reviewers independently extracted
      data and assessed study quality. A decision tree model was used to model the
      diagnosis decision and a Markov model was developed for the management of
      patients with suspected coronary artery disease. Costs for the treatments and
      interventions within strategies were derived from the literature and expressed in
      2001-02 pounds sterling. Quality-adjusted life-year (QALY) weights for the
      different Markov model states were also obtained from the literature. RESULTS:
      Twenty-one diagnostic and 46 prognostic studies were included, plus two studies
      comparing SPECT with electrocardiography (ECG)-gated SPECT and one study
      comparing SPECT with attenuation-corrected SPECT. The diagnostic values of SPECT
      were generally higher than those of stress ECG, indicating that SPECT provided a
      better diagnostic performance. SPECT also provided higher positive and lower
      negative likelihood ratios than stress ECG but heterogeneity was evident among
      studies. The subgroup of studies including patients with previous MI tended to
      report a better diagnostic performance for SPECT than stress ECG, but there were
      too few studies to assess this reliably. The extent and size of the perfusion
      defect, and whether reversible or fixed, were important factors in predicting
      future cardiac events such as cardiac death or non-fatal MI. SPECT may be able to
      identify lower risk patients for whom coronary angiography (CA) might be avoided.
      Normal SPECT scans were associated with a benign prognosis and the option of
      medical rather than invasive management. Four studies of patients post-MI
      reported SPECT to be valuable in stratifying patients into at-risk groups for
      further cardiac events. The two studies comparing SPECT with ECG-gated SPECT, one
      diagnostic and the other prognostic, found in favour of gated SPECT. The study
      comparing SPECT with attenuation-corrected SPECT reported the latter to be more
      accurate. The systematic review of economic evaluations indicated that strategies
      involving SPECT were likely either to be dominant or to produce more QALYs at an
      acceptable cost. There was less agreement about which of the strategies involving
      SPECT was optimal. The model suggested that, for low prevalence, the incremental
      cost per unit of output (true positives diagnosed, accurate diagnosis, QALY) for
      the move from stress ECG-SPECT-CA and from stress ECG-CA to SPECT-CA might be
      considered worthwhile. Even after allowing for different values for sensitivity
      or specificity, the least costly and least effective strategy was stress ECG
      SPECT-CA. The sensitivity analysis suggested that the cost-effectiveness of SPECT
      CA improved if it was assumed that SPECT results allowed for the adoption of a
      management strategy without recourse to CA. As the time horizon reduced, the
      incremental cost per QALY increased (as the cost of initial diagnosis and
      treatment were not offset by survival and quality of life gains). CONCLUSIONS:
      There was a considerable variability in terms of measurement of outcomes,
      management, setting and patient characteristics, however the direction of
      evidence tended to favour SPECT in terms of test sensitivity, although these
      conclusions are based on a relatively small number of diagnostic studies. SPECT,
      in a variety of settings and patient populations, provided valuable independent
      and incremental prognostic information to that provided by stress ECG and/or CA
      that helped to risk-stratify patients and influence the way in which their
      condition was managed. However, all of the prognostic studies were observational
      studies and may be biased by unknown confounding factors. Although the ECG-gated
      and attenuation-corrected SPECT findings seem promising, it is difficult to draw
      conclusions from so few studies. Further research is needed on the effectiveness
      and cost-effectiveness, diagnostically and prognostically, of (a) gated and
      attenuation-corrected SPECT compared with standard SPECT, (b) standard SPECT
      compared with stress echocardiography and (c) the uncertainty surrounding the
      results presented in the cost-effectiveness analysis.

PMID- 15248939
TI  - VenUS I: a randomised controlled trial of two types of bandage for treating
      venous leg ulcers.
AB  - OBJECTIVES: To compare the clinical and cost-effectiveness of two different
      compression bandages for the healing of venous leg ulcers. DESIGN: A pragmatic,
      randomised controlled trial with an economic evaluation. SETTING: Community,
      district nurse-led services; community leg ulcer clinics; hospital leg ulcer
      clinics with community outreach. A range of urban and rural settings in England
      and Scotland. PARTICIPANTS: Patients with a venous leg ulcer of at least 1-week's
      duration, at least 1 cm in length or width and an ankle:brachial pressure index
      of at least 0.8. INTERVENTIONS: The four-layer bandage (4LB) (which is multilayer
      elastic compression) compared with the short-stretch bandage (SSB) (multilayer,
      inelastic compression). MAIN OUTCOME MEASURES: The primary end-point was complete
      healing of all the ulcers on the trial leg. Secondary outcomes were the
      proportion of patients healed at 12 and 24 weeks, rate of recurrence, costs of
      leg ulcer treatment and quality of life. RESULTS: Between April 1999 and December
      2000 the trial recruited 387 people aged from 23 to 97 years at trial entry. The
      majority of patients in this trial (82%; 316/387) had a reference ulcer of area
      </=10 cm(2). To test the difference over time of Kaplan--Meier curves for the two
      bandage groups, the distribution of the cumulative times to healing of
      individuals in the two trial groups was compared using the log-rank test. The
      difference in the distribution of cumulative healing times between the
      individuals in the two groups was not statistically significant at the 5% level.
      Adjusting for the effects of variables which may influence healing (centre,
      baseline ulcer area, duration, episodes, ankle mobility, weight) in a Cox
      proportional hazards model, a statistically significant treatment effect in
      favour of the 4LB was identified. At any point in time, the probability of
      healing for individuals in the SSB treatment arm is significantly lower than that
      for people treated with the 4LB. Our base case economic analysis showed that the
      4LB is the dominant strategy, that is, it is associated with a greater health
      benefit and lower costs than the SSB, although the differences are not
      statistically significant. This result is explained largely by the greater number
      of community nurse visits required by participants in the short-stretch arm.
      CONCLUSIONS: The 4LB, which is currently the UK standard compression bandage for
      people with venous leg ulcers, was more clinically and cost-effective than the
      SSB. The bandage costs were less important than the costs of treatment visits,
      and patients in SSBs required more treatment overall. Generally, this trial
      supports the use of the 4LB in preference to the SSB. Recommendations for future
      research include: exploration of the relationship between bandager skill,
      application technique and ulcer healing; the relative cost-effectiveness of
      community leg ulcer clinics; and the study of nurse decision-making in venous
      ulcer management.

PMID- 15248940
TI  - Signal processing and calibration procedures for in situ diode-laser absorption
      spectroscopy.
AB  - Gas analyzers based on tunable diode-laser spectroscopy (TDLS) provide high
      sensitivity, fast response and highly specific in situ measurements of several
      atmospheric trace gases simultaneously. Under optimum conditions even a shot
      noise limited performance can be obtained. For field applications outside the
      laboratory practical limitations are important. At ambient mixing ratios below a
      few parts-per-billion spectrometers become more and more sensitive towards noise,
      interference, drift effects and background changes associated with low level
      signals. It is the purpose of this review to address some of the problems which
      are encountered at these low levels and to describe a signal processing strategy
      for trace gas monitoring and a concept for in situ system calibration applicable
      for tunable diode-laser spectroscopy. To meet the requirement of quality
      assurance for field measurements and monitoring applications, procedures to check
      the linearity according to International Standard Organization regulations are
      described and some measurements of calibration functions are presented and
      discussed.

PMID- 15248941
TI  - Synthesis and infrared and fluorescence spectra of new europium and terbium
      polynuclear complexes with an amide-based 1,10-phenanthroline derivative.
AB  - An amide-based 1,10-phenanthroline (phen) derivative and its complexes with
      europium(III) and terbium(III) ions were synthesized. The complexes were
      characterized by elemental analysis, infrared spectra and conductivity. The
      europium and terbium ions were coordinated by O atoms of C=O, Ar-O-C and N atoms
      of phen. The fluorescence properties of the complexes in THF, dioxane, MeCN and
      DMF were investigated. Under the excitation of UV light, these complexes
      exhibited characteristic fluorescence of europium and terbium ions. The solvent
      factors influencing the fluorescent intensity were discussed.

PMID- 15248942
TI  - Steric-controlled excimer formation in naphthalene analogues of chalcone.
AB  - Naphthalene analogues of chalcone (typical vinylarenes) are well known for their
      intramolecular charge transfer (CT) process. The all four possible isomers NC1,
      NC2, NC3 and NC4 were observed to give structure-less broad CT bands, whereas,
      excimer formation at higher concentration was reported only for NC4 [Res. Chem.
      Intermed. 25 (1999) 903]. However, conventional GMMX calculation data reveals
      that the naphthalene portion of all the isomers are planar, hence, excimer
      emission is expected from all of them, i.e., if NC4 can form an excimer, then the
      rests are also capable of doing it. In this paper we have actually succeeded in
      resolving the excimer peaks for all these four isomers by optimization of
      concentration, though the extent of excimer formation was observed to be the
      maximum for NC4. These differential tendencies of excimer formation can be
      explained by the change in extent of intermolecular stacking interaction of the
      naphthalene moieties. Variation occurs here due to steric perturbation arising
      from the specific orientation of the near resident non-planar aroyl component
      with respect to the naphthalene moiety.

PMID- 15248943
TI  - Preparation and application of cysteine-capped ZnS nanoparticles as fluorescence
      probe in the determination of nucleic acids.
AB  - Cysteine-capped ZnS nanometer-sized fluorescent particles were produced by a
      colloidal aqueous synthesis. The functionalized nanoparticles are water-soluble
      and suitable for biological application. A synchronous fluorescence method has
      been developed for the rapid determination of DNA with functionalized nano-ZnS as
      a fluorescence probe, based on the synchronous fluorescence enhancement of
      cysteine-capped nano-ZnS in the presence of DNA. When Deltalambda =190 nm,
      maximum synchronous fluorescence is produced at 267 nm at pH 5.12. Under optimum
      conditions, the synchronous fluorescence intensity is proportional to the
      concentration of nucleic acids in the range 0.1-1.2 microg ml(-1) for calf thymus
      DNA, 0.1-0.6 microg ml(-1) for fish sperm DNA. The corresponding detection limit
      is 32.9 ng ml(-1) for calf thymus DNA and 24.6 ng ml(-1) for fish sperm DNA. This
      method is simple, inexpensive, rapid and sensitive. The recovery and relative
      standard deviation are satisfactory.

PMID- 15248944
TI  - The detection of drugs of abuse in fingerprints using Raman spectroscopy II:
      cyanoacrylate-fumed fingerprints.
AB  - This paper describes the application of Raman spectroscopy to the detection of
      exogenous substances in cyanoacrylate-fumed fingerprints. The scenario considered
      was that of an individual handling a substance and subsequently depositing a
      contaminated fingerprint. These fingerprints were enhanced by cyanoacrylate
      fuming, a process in which a layer of white cyanoacrylate polymer is deposited on
      the fingerprint material, enabling visual detection. Five drugs of abuse (codeine
      phosphate, cocaine hydrochloride, amphetamine sulphate, barbital and nitrazepam)
      and five non-controlled substances of similar appearance, which may be used in
      the adulteration of drugs of abuse (caffeine, aspirin, paracetamol, starch and
      talc), were used. The substances studied could be clearly distinguished using
      their Raman spectra and were all successfully detected in cyanoacrylate-fumed
      fingerprints. Photobleaching was necessary to reduce the fluorescence background
      in the spectra of some substances. Raman spectra obtained from the substances in
      cyanoacrylate-fumed fingerprints were of a similar quality to spectra obtained
      from the substances under normal sampling conditions, however, interfering Raman
      bands arising from the cyanoacrylate polymer were present in the spectra. In most
      cases the only interfering band was the C triple bond N stretching mode of the
      polymer, and there were no cases where the interfering bands prevented
      identification of the substances. If necessary, the interfering bands could be
      successfully removed by spectral subtraction. The most difficult aspect of the
      detection of these substances in cyanoacrylate-fumed fingerprints was visually
      locating the substance in the fingerprint beneath the polymer layer in order to
      obtain a Raman spectrum.

PMID- 15248945
TI  - Absorption spectrometric study of charge transfer complex formation between 4
      acetamidophenol (paracetamol) and a series of quinones including vitamin K3.
AB  - The formation of charge transfer (CT) complexes of 4-acetamidophenol (commonly
      called 'paracetamol') and a series of quinones (including Vitamin K3) has been
      studied spectrophotometrically in ethanol medium. The vertical ionisation
      potential of paracetamol and the degrees of charge transfer of the complexes in
      their ground state has been estimated from the trends in the charge transfer
      bands. The oscillator and transition dipole strengths of the complexes have been
      determined from the CT absorption spectra at 298 K. The complexes have been found
      by Job's method of continuous variation to have the uncommon 2:1
      (paracetamol:quinone) stoichiometry in each case. The enthalpies and entropies of
      formation of the complexes have been obtained by determining their formation
      constants at five different temperatures.

PMID- 15248946
TI  - Small interacting peptides. Part II: Interaction of cyclohexapeptides with
      immobilised model peptides. Comparison of infrared investigations, principal
      components analysis and force field calculations.
AB  - The interaction of cyclic peptides with surface-bound model peptides was
      investigated by ATR-FTIR spectroscopy, principal components analysis and force
      field calculations. Information about the interacting functional COOH, COO-, and
      NH3+ groups and the peptide backbone was gained through a set of
      cyclohexapeptides (seven of the type c(X1KX2KX3K) (K = L-lysine) and one of the
      type c(X1KX2KX3k) (k = D-lysine), which are interacting with L-arginine- or
      tripeptide-coated Si-ATR crystals. All measurements were performed in aqueous
      solutions. Spectra evaluation in the range 1800-1500 cm(-1) was done by band and
      principal components analysis (PCA). Only adsorbed molecules were present in
      these spectra. The coatings were investigated by ATR-FTIR spectroscopy too in
      order to characterise their functional groups. Based on this knowledge, the
      spectra of the interacting partners could be evaluated in relation to
      cyclohexapeptides and coatings. As a result, it was possible to identify the
      distinct differences in the bonding behaviour of the various peptides.

PMID- 15248947
TI  - EPR, IR and electronic spectral studies on Mn(II), Co(II), Ni(II) and Cu(II)
      complexes with a new 22-membered azamacrocyclic [N4] ligand.
AB  - The complexes of transition metal ions with an azamacrocyclic tetradentate
      nitrogen donor [N4] ligand viz. 2,6,12,16,21,22-hexaaza;3,5,13,15
      tetramethyltricyclo[15.3.1.1(7-11)] docosa;1(21),2,5,7,9,11(22),12,15,17,19
      decaene (L) have been synthesized. All the complexes were found to have general
      composition M(L)X2 [where M = manganese(II), cobalt(II), nickel(II) and
      copper(II) and X = Cl- & NO3-]. All the complexes are characterized by the
      elemental analysis, molar conductance measurements, magnetic susceptibility
      measurements, mass, 1H NMR, IR, electronic, EPR spectral and cyclic voltammetric
      studies. An octahedral geometry was assigned for Mn(II), Co(II) and Ni(II)
      complexes and tetragonal for Cu(II) complexes. The biological actions of the
      ligand and complexes have been screened in vitro against many bacteria and
      pathogenic fungi to study their comparative capacity to inhibit the growth.

PMID- 15248948
TI  - Stereochemistry of new nitrogen containing heterocyclic aldehyde. Part XI. Novel
      ligational behaviour of quinoline as chelate ligand toward transition metal ions.
AB  - Novel complexes of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and UO2(II)
      with a new Schiff base derived from 8-hydroxy-7-quinolinecarboxaldehyde and 2
      aminoethanethiol (LH2) (system name: 2-(8-hydroxy-7-carboxalimino)ethanethiol.)
      have been prepared and characterized on the basis of analytical, thermal,
      magnetic moment, infrared, electronic, NMR and EPR spectral data. From the
      analytical, NMR and thermal data and stoichiometry of the complexes indicate that
      LH2 act as a dibasic tridentate ligand with ONS donors towards all the metal
      ions. The magnetic moment, electronic and EPR spectral data commensurate that the
      Mn(II), Fe(II), Ni(II) and UO2(II) complexes are dimeric with octahedral
      configuration while the Cu(II) and Zn(II) complexes are monomeric with square
      planar and tetrahedral geometries, respectively. Various ligand field parameters
      Dq, B and beta for complex 5 was calculated. The complexes 3+4 have lower
      symmetries and the amount of distortion in terms of DT/DQ applying NSH
      "Hamiltonian Theory" has been evaluated which indicate that the complexes are
      moderately distorted.

PMID- 15248949
TI  - Spectrophotometric microdetermination of nefopam, mebevrine and
      phenylpropanolamine hydrochloride in pharmaceutical formulations using alizarins.
AB  - Simple and rapid spectrophotometric procedures have been established for
      quantitation of nefopam hydrochloride (NF) mebevrine hydrochloride (MB) and
      phenylpropanolamine hydrochloride (PP). The procedures are based on the reaction
      between the examined drugs (NF, MB and PP) and alizarin (I), alizarin red S (II),
      alizarin yellow G (III) and quinalizarin (IV) producing ion-pair complexes which
      can be measured at the optimum wavelength. The optimization of the reaction
      conditions is investigated. Beer's law is obeyed in the concentration ranges 0.5
      30.0 microg ml(-1). The molar absorptivity, Sandell sensitivity, detection and
      quantification limits are also calculated. The correlation coefficient was > or
      =0.9988 (n=6) with a relative standard deviation (R.S.D.) of < or =1.3, for six
      determinations of 20 microg ml(-1). The methods are successfully applied to the
      determination of NF, MB and PP in their pharmaceutical formulations.

PMID- 15248950
TI  - IR, UV-Vis, magnetic and thermal characterization of chelates of some
      catecholamines and 4-aminoantipyrine with Fe(III) and Cu(II).
AB  - The dopamine derivatives participate in the regulation of wide variety of
      physiological functions in the human body and in medication life. Increase and/or
      decrease in the concentration of dopamine in human body reflect an indication for
      diseases such as Schizophrenia and/or Parkinson diseases. Alpha-methyldopa (alpha
      MD) in tablets is used in medication of hypertension. The Fe(III) and Cu(II)
      chelates with coupled products of adrenaline hydrogen tartarate (AHT), levodopa
      (LD), alpha-MD and carbidopa (CD) with 4-aminoantipyrine (4-AAP) are prepared and
      characterized. Different physico-chemical methods like IR, magnetic and UV-Vis
      spectra are used to investigate the structure of these chelates. Fe(III) form 1:2
      (M:catecholamines) chelates while Cu(II) form 1:1 chelates. Catecholamines behave
      as a bidentate mono- or dibasic ligands in binding to the metal ions. IR spectra
      show that the catecholamines are coordinated to the metal ions in a bidentate
      manner with O,O donor sites of the phenolic -OH. Magnetic moment measurements
      reveal the presence of Fe(III) chelates in octahedral geometry while the Cu(II)
      chelates are square planar. The thermal decomposition of Fe(III) and Cu(II)
      complexes is studied using thermogravimetric (TGA) and differential thermal
      analysis (DTA) techniques. The water molecules are removed in the first step
      followed immediately by decomposition of the ligand molecules. The activation
      thermodynamic parameters, such as, energy of activation, enthalpy, entropy and
      free energy change of the complexes are evaluated and the relative thermal
      stability of the complexes are discussed.

PMID- 15248951
TI  - Two-dimensional fluorescence correlation spectroscopy II: spectral analysis of
      derivatives of anthracene and pyrene in micellar solutions.
AB  - Generalized two-dimensional (2D) correlation spectroscopy has been applied to the
      analysis of fluorescence spectra in two micellar systems: (1) a mixture of pyrene
      and 1,3,6,8-pyrenetetrasulfonic acid in the cationic micellar solutions of
      cetyltrimethylammonium chloride (CTAC) and (2) a mixture of pyrene and 9
      anthracencepropionic acid in anionic micellar solutions of sodium dodecyl sulfate
      (SDS). Fluorescence quenching is employed as a perturbation mode for causing
      intensity changes in fluorescence bands (quenching perturbation). Iodide ion (I-)
      is used as a quencher in the former system, and cetyl pridinium chloride (CPC) is
      used in the latter. Vibronic bands in the complicated fluorescence spectra of the
      mixture of the analytes were successfully resolved. It is shown that asynchronous
      maps are especially useful for spectral resolution enhancement when the quenching
      perturbation is employed in 2D fluorescence correlation spectroscopy.
      Furthermore, the information about the order of response of the bands to
      quenching is obtained by comparing the signs of synchronous and asynchronous
      cross-peaks.

PMID- 15248952
TI  - Electron donor-acceptor complexes of 2,3-dichloro-5-nitro-1,4-naphthoquinone with
      some methyl substituted anilines: formation of 1:2 (A:D) complexes.
AB  - The donor-acceptor complexes between 2,3-dichloro-5-nitro-1,4-naphthoquinone
      (DClNNQ) and some methyl substituted anilines were investigated by
      spectrophotometric method. This investigation was carried out in three different
      chlorinated solvents viz., chloroform, dichloromethane and 1,2-dichloroethane.
      Experimental evidences shows the formation of 1:2 (A:D) complexes but not 1:1
      complexes. The calculated values of the oscillator strength and transition moment
      confirms this suggestion. The stoichiometry of the complexes was unaffected by
      the variation of temperature over a small interval and also change in solvent.
      The thermodynamic and spectroscopic parameters were evaluated in all the three
      solvents for the formation of CT-complexes. The influence of used solvents on the
      thermodynamic and spectroscopic parameters was investigated. The strength of the
      donors was also investigated.

PMID- 15248953
TI  - Solvatochromic correlations and ground- and excited-state dipole moments of
      curcuminoid dyes.
AB  - Experimental dipole moments of curcumin (1) and of its parent compound
      dicinnamoylmethane (2) were determined in dioxane and benzene, respectively.
      Theoretical dipole moments were calculated using a combination of the PPP method
      (pi-moment) and a vector sum of the sigma-bond moments (sigma-moment) as well as
      by the ZINDO/1 method. Solvatochromic correlations were used to obtain the
      experimental first excited singlet-state dipole moments. The experimental
      electronic absorption spectra were compared with the calculated transitions.

PMID- 15248954
TI  - A new method for the determination of the critical micelle concentration of
      Triton X-100 in the absence and presence of beta-cyclodextrin by resonance
      Rayleigh scattering technology.
AB  - A new method for the determination of the critical micelle concentration (CMC) of
      Triton X-100 in aqueous solution and beta-cyclodextrin solution by resonance
      Rayleigh scattering (RRS) has been developed. The method is based on the
      measurement of the RRS intensity of different concentration of Triton X-100 in
      aqueous solution and beta-cyclodextrin solution (6.0 x 10(-4) mol l(-1)). When
      the RRS intensities were plotted against the concentration of Triton X-100, an
      inflection point appeared at the Triton X-100 concentration of 5.0 x 10(-4) mol
      l(-1) in aqueous solution and 1.1 x 10(-3) mol l(-1) in beta-cyclodextrin
      solution, respectively. These values of concentration corresponded to the CMC of
      Triton X-100 in aqueous solution and beta-cyclodextrin solution, which also
      agreed closely with the results reported by surface tension and UV-Vis absorption
      spectrophotometry. Therefore, the present RRS method is very convenient, rapid
      and accurate and can be used as a new technology for the determination of CMC
      values of surfactants without any probe. The relationship between the RRS
      intensity and the concentration, aggregate state and the aggregate molecular size
      of Triton X-100 has been primarily discussed.

PMID- 15248955
TI  - Cw-laser thermal lens spectrometry in binary mixtures of water and organic
      solvents: composition dependence of the steady-state and time-resolved signals.
AB  - The thermal lens effect obtained in binary liquid systems composed of water and
      ethanol, propanol and acetonitrile has been investigated. The dependence of dn/dT
      upon the solvent volume fraction follows polynomials up to sixth order and cannot
      be precisely predicted using the additive rule. The sensitivity of the thermal
      lens method upon the addition of organic solvent in water varies as the
      temperature-dependent refractive index gradient to thermal conductivity ratio of
      the mixture provided that the signal is sampled correctly. Otherwise, especially
      when steady-state experiments are carried out, the thermally induced
      concentration gradient, known as the Soret effect, can change the thermo-optical
      properties of the solution locally in the irradiated area and produce an
      additional signal. This effect depends on the solvent and is maximum at low
      solvent composition. At the critical solvent volume fraction of 0.1-0.15, the
      Soret component may represent up to 25% of the pure thermal lens signal and has a
      time constant which is 200-400 times greater than the characteristic time
      constant of the thermal lens.

PMID- 15248956
TI  - Total assignment and structure in solution of tetrandrine by NMR spectroscopy and
      molecular modelling.
AB  - High-resolution 1- and 2D NMR spectra of tetrandrine and molecular modelling were
      employed to characterise its structure in solution. Complete and unambiguous
      assignment of all proton and carbon resonance signals is reported. Scalar
      couplings were determined from dihedral angles with the Karplus equation. Inter
      proton distances were evaluated from NOE correlation peaks. Comparison of
      simulated and X-ray conformations of tetrandrine reveals only small differences.

PMID- 15248957
TI  - Electrochemical impedance spectroscopy and electron spin resonance
      characterization of the conductive state of parasexiphenylene electrochemically
      intercalated with sodium.
AB  - The electrochemical intercalation of sodium ions into parasexiphenylene (PSP) was
      studied by electron spin resonance (ESR) and electrochemical impedance
      spectroscopy (EIS). These complementary techniques give informations about the
      conduction state of the host material as a function of the doping rate both in
      the intercalation and deintercalation processes. These data were compared to the
      previous works concerning the intercalation of alkaline ions into
      polyparaphenylene (PPP).

PMID- 15248958
TI  - Static and dynamic model for 4-aminodiphenyl fluorescence quenching by
      carbontetrachloride in hexane.
AB  - The fluorescence quenching of 4-aminodiphenyl (4ADP) with chloromethanes (CH2Cl2,
      CHCl3 and CCl4) have been studied in solvents of different polarity and
      viscosity. The quenching rate constants (kq) have been determined in all
      solvents. For CCl4 and CHCl3 quenching, the kq depends on solvent viscosity
      whereas for CH2Cl2, the kq values show a mixed trend with no clear-cut variation
      with either solvent polarity or solvent viscosity. Quenching mechanism involving
      an intermediate donor-acceptor complex formation is proposed for CH2Cl2
      quenching. A positive deviation was observed in the Stern-Volmer (SV) plot for
      CCl4 quenching in hexane. The static-dynamic model could explain this.

PMID- 15248959
TI  - Surface-enhanced Raman scattering of a series of n-hydroxybenzoic acids (n = P, M
      and O) on the silver nano-particles.
AB  - Surface-enhanced Raman scattering (SERS) spectra of a series of n-hydroxybenzoic
      acids (n-HBA, n = P, M and O) adsorbed on the silver nano-particles were studied,
      respectively, in the silver colloidal solution and on the dried silver-coated
      filter paper. On the same substrate, the different molecules' SERS spectra were
      different, while on the different substrates the same molecules' SERS spectra
      were also different. Significant changes were found in the SERS spectra of PHBA
      molecules adsorbed on the two substrates, and the changes found in MHBA's spectra
      on two substrates were next to PHBA's, while almost no changes were found in the
      spectra of OHBA molecules. Moreover, it was found, on the filter paper, that the
      SERS spectra of the same molecules would change with the coverage density of the
      silver nano-particles. The analyses showed that the origins of these changes were
      the different adsorption behavior of molecules adsorbed on the silver nano
      particles. Because in these three molecules the relative positions of the
      carboxyls and hydroxyls on the benzenes are different, the adsorption behaviors
      of these three molecules adsorbed on the silver surfaces are also different. The
      experimental results suggest that the surface characteristic of the substrate and
      the surface configuration of the adsorbate could exert a great influence on the
      adsorption behavior of the adsorbates on the substrates.

PMID- 15248960
TI  - Raman microscopy of selected tungstate minerals.
AB  - A series of tungstate bearing minerals including scheelite, stolzite, ferberite,
      hubnerite, wolframite, russellite, tungstenian wulfenite and cuprotungstite have
      been analyzed by Raman microscopy. The results of the Raman spectroscopic
      analysis are compared with published data. These minerals are closely related and
      often have related paragenesis. Raman microscopy enables the selection of
      individual crystals of these minerals for spectroscopic analysis even though
      several of the minerals can be found in the same matrix because of the pargenetic
      relationships between the minerals. The Raman spectra are assigned according to
      factor group analysis and related to the structure of the minerals. These
      minerals have characteristically different Raman spectra. The nu1(Ag) band is
      observed at 909 cm(-1) and although the corresponding nu1(Bu) vibration should be
      inactive a minor band is observed around 894 cm(-1). The bands at 790 and 881 cm(
      1) are associated with the antisymmetric and symmetric Ag modes of terminal WO2.
      The band at 695 cm(-1) is interpreted as an antisymmetric bridging mode
      associated with the tungstate chain. The nu4(Eg) band was absent for scheelite.
      The bands at 353 and 401 cm(-1) are assigned as either deformation modes or as
      r(Bg) and delta(Ag) modes of terminal WO2. The band at 462 cm(-1) has an
      equivalent band in the infrared at 455 cm(-1) assigned as delta(as)(Au) of the
      (W2O4)n chain. The band at 508 cm(-1) is assigned as nu(sym)(Bg) of the (W2O4)n
      chain.

PMID- 15248961
TI  - Spectrophotometric determination of paracetamol with microwave assisted alkaline
      hydrolysis.
AB  - A novel and rapid spectrophotometric method for the determination of paracetamol
      is proposed in this paper. The proposed method is based on the microwave assisted
      alkaline hydrolysis of paracetamol to p-aminophenol that reacts with S2- in the
      presence of Fe3+ as oxidant to produce a methylene blue-like dye having an
      absorptivity maximum at 540 nm. The experiment showed that paracetamol could be
      hydrolysed quantitatively to p-aminophenol in only 1.5 min under radiation power
      640 W using a microwave in NaOH medium. The system obeys Beer's law in the range
      of 0-3.0 x 10(-4) mol l(-1) paracetamol. The molar absorptivity and Sandell's
      sensitivity were found to be 3.2 x 10(-3) l mol(-1) cm(-1) and 0.047 microg cm(
      2), respectively. The relative standard deviation (n=11) was 1.7% for 8.0 x 10(
      5) mol l(-1) paracetamol. The method has been applied successfully to analysis of
      paracetamol in pharmaceutical preparation.

PMID- 15248962
TI  - A long lifetime chemical sensor: study on fluorescence property of fluorescein
      isothiocyanate and preparation of pH chemical sensor.
AB  - The fluorescence property of fluorescein isothiocyanate (FITC) in acid-alkaline
      medium was studied by spectrofluorimetry. The characteristic of FITC response to
      hydrogen ion has been examined in acid-alkaline solution. A novel pH chemical
      sensor was prepared based on the relationship between the relative fluorescence
      intensity of FITC and pH. The measurement of relative fluorescence intensity was
      carried out at 362 nm with excitation at 250 nm. The excellent linear
      relationship was obtained between relative fluorescence intensity and pH in the
      range of pH 1-5. The linear regression equation of the calibration graph is F =
      66.871 + 6.605 pH (F is relative fluorescence intensity), with a correlation
      coefficient of linear regression of 0.9995. Effects of temperature, concentration
      of FITC on the response to hydrogen ion had been examined. It was important that
      this chemical sensor was long lifetime, and the property of response to hydrogen
      ion was stable for at least 70 days. This pH sensor can be used for measuring pH
      value in water solution. The accuracy is 0.01 pH unit. The results obtained by
      the pH sensor agreed with those by the pH meter. Obviously, this pH sensor is
      potential for determining pH change real time in biological system.

PMID- 15248963
TI  - Correlation of the oxidation state of cerium in sol-gel glasses as a function of
      thermal treatment via optical spectroscopy and XANES studies.
AB  - Sol-gel glass matrices containing lanthanides have numerous technological
      applications and their formation involves several chemical facets. In the case of
      cerium, its ability to exist in two different oxidation states or in mixed
      valence state provides additional complexities for the sol-gel process. The
      oxidation state of cerium present during different facets of preparation of sol
      gel glasses, and also as a function of the starting oxidation state of cerium
      added, were studied both by optical spectroscopy and X-ray absorption near-edge
      structures (XANES). The findings acquired by each approach were compared. The
      primary focus was on the redox chemistries associated with sample preparation,
      gelation, and thermal treatment. When Ce3+ is introduced into the starting sols,
      the trivalent state normally prevails in the wet and room temperature-dried gels.
      Heating in air at >100 degrees C can generate a light yellow coloration with
      partial oxidation to the tetravalent state. Above 200 degrees C and up to
      approximately 1000 degrees C, cerium is oxidized to its tetravalent state. In
      contrast, when tetravalent cerium is introduced into the sol, both the wet and
      room temperature-dried gels lose the yellow-brown color of the initial ceric
      ammonium nitrate solution. When the sol-gel is heated to 110 degrees C it turns
      yellowish as the cerium tends to be re-oxidized. The yellow color is believed to
      represent the effect of oxidation and oligomerization of the cerium-silanol units
      in the matrix. The luminescence properties are also affected by these changes,
      the details of which are reported herein.

PMID- 15248964
TI  - An MP2 and DFT study of heterocyclic hydrogen complexes CnHmY-HX with n=2, m=4 or
      5, Y=O, S or N and X=F or Cl.
AB  - We present a theoretical study through MP2 ab initio molecular orbital
      calculations and B3LYP density functional theory with the 6-311++G(d,p) basis set
      of the heterocyclic hydrogen complexes, CnHmY-HX, where CnHmY = C2H4O, C2H5N and
      C2H4S, and X=F or Cl. This study aided in the elucidation the main changes in the
      structural, electronic and the vibrational properties in isolated species, due
      the hydrogen complexes formation, CnHmY-HX, revealing systematic tendencies in
      these chemical systems studied. The complexes has CS symmetry, with the HX
      subunit lying in the plane perpendicular to that of CYC nuclei of heterocyclic
      and acting as proton donor in forming a hydrogen bond to the heteroatom, Y. A
      weak secondary interaction between the CH2 groups of heterocyclics and the X
      atoms in HX causes a significant nonlinearity of the primary hydrogen bond. The
      hydrogen bond linearity deviations in these complexes due to secondary
      interactions are represented by theta angle. The MP2 intermolecular distances of
      complexes C2H5N-HF, C2H4O-HF and C2H4S-HF correspond the 1.652, 1.671 and 2.164
      A, respectively, these results are in excellent agreement with experimental
      results of 1.700 and 2.193 A found for the last two complexes. In the same way,
      the MP2 values to theta angle, 14.7, 19.1 and 16.8 degrees, has a better
      reproduction in the experimental results of 16.5, 21.0 and 16.8 degrees, get to
      the C2H4O-HCl, C2H4S-HCl and C2H4S-HF complexes, respectively.

PMID- 15248965
TI  - A3Pi1u<--X1Sigmag+ laser photoacoustic spectroscopy of Br2 vapor in the extreme
      red wavelength region 665-720 nm.
AB  - The A3Pi1u<--X1Sigmag+ photoacoustic spectrum of Br2 vapor has been studied and
      vibronic analysis performed using earlier data available for this system of bands
      from optical spectroscopy in the region 665-720 nm. The vibronic levels involved
      in these transitions are 4< or =v'< or =21 and 1< or =v''< or =4. The relative
      photoacoustic intensities of the vibronic bands have been used in estimating the
      non-radiative relaxation rate from vibrational levels of A3Pi(1u) state. The non
      radiative relaxation is found to be a nonlinear function of the upper state
      vibrational quantum number. The radiative rate constants for the A3Pi(1u) state
      vibrational levels have been compared with the corresponding non-radiative
      constants obtained from present work. Non-radiative decay rate constants for the
      vibrational levels of A3Pi(1u) state have been experimentally determined for the
      first time from photoacoustic spectrum of Br2 vapor in the extreme red region.

PMID- 15248966
TI  - Vibrational frequencies and structural determination of adamantane.
AB  - The normal mode frequencies and corresponding vibrational assignments of
      adamantane in Td symmetry are examined theoretically using the Gaussian 98 set of
      quantum chemistry codes. All normal modes were successfully assigned to one of
      eight types of motion predicted by a group theoretical analysis. The vibrational
      modes of the deuterated form of adamantane were also calculated and compared
      against experimental data.

PMID- 15248967
TI  - Complexing properties of nucleic-acid constituents adenine and guanine complexes.
AB  - Cobalt, nickel and copper complexes of adenine and guanine, as nucleic-acid
      constituents, were prepared. The adenine and guanine complexes are of tetrahedral
      and octahedral geometries, respectively. All are of high spin nature. The nickel
      complexes are of 2:1 metal:ligand ratio with Ni...Ni direct interaction in the
      guanine complex. The coordination bonds of adenine metal complexes are calculated
      and follow the order: Cu(II)-adenine < Ni(II)-adenine < Co(I)-adenine. The Cu(II)
      adenine complex is the stronger following the softness of the copper, while that
      of guanine is less covalent. The copper complexes are with stronger axial field.
      The differential thermal analysis (DTA) and TGA of the complexes pointed to their
      stability. The mechanism of the thermal decomposition is detected. The
      thermodynamic parameters of the dissociation steps are evaluated. The complexes
      are of semi-conducting behaviour for their technical applications. Empirical
      equations are deduced between the electrical conducting and the energy of
      activation of the complexes.

PMID- 15248968
TI  - Tautomeric structures, electronic spectra, acid-base properties of some 7-aryl
      2,5-diamino-3(4-hydroxyphenyazo)pyrazolo[1,5-a]pyrimidine-6-carbonitriles, and
      effect of their copper(II) complex solutions on some bacteria and fungi.
AB  - Infrared and electronic spectra were used to investigate the tautomerism of some
      azo compounds, in both the solid and solution states. It was found that the
      compounds exist in azo<==>hydrazone tautomeric equilibrium in solid and in
      solutions. The different bands displayed in the electronic spectra of the
      compounds in various organic solvents are assigned to the suitable electronic
      transitions. The solvatochromic behavior of the compounds was investigated by
      studying their visible spectra in pure and mixed organic solvents. DeltaG and
      formation constant, Kf, values of the molecular complexes formed in solution have
      been determined. Effect of concentration of the compounds in DMF and EtOH
      solutions has been investigated. The basicity and acidity constants of the
      different compounds were determined from the spectra of these compounds in
      aqueous-ethanolic solutions of varying pH values. Some complexes of copper(II)
      with these compounds in solution were tested as for their antibacterial and
      antifungal activity.

PMID- 15248970
TI  - Two-dimensional infrared spectroscopy study on phase transition and structural
      variations of a hydrogen-bonded liquid crystal.
AB  - Infrared (IR) spectra have been measured for a liquid crystal (LC) consisting of
      one trans-butene diacid (BD) molecule as a proton donor and two 4-(2,3,4
      tridecyloxybenzoyloxy)-4'-stilbazoles (DBS) molecules as a proton acceptor
      (DBS:BD:DBS) linked together with each other by inter-molecular hydrogen bonds
      over a temperature range from 20 to 120 degrees C to explore its phase transition
      and heat-induced structural variations. The temperature-dependent IR spectra have
      shown that the inter-molecular hydrogen bonds are stable in the liquid
      crystalline phase but become slightly decoupled with temperature increasing. Two
      kinds of two-dimensional (2D) correlation spectroscopy, variable-variable (VV)
      and sample-sample (SS) 2D spectroscopy, have been employed to analyze the
      observed temperature-dependent spectral variations more efficiently. The SS 2D
      correlation analysis in the spectral range of 2700-1800 cm(-1) has demonstrated
      that a change in hydrogen bonds in the LC starts from 40 degrees C, which is not
      clarified by differential scanning calorimetry (DSC) and conventional IR and
      Raman spectroscopic analyses. On the other hand, the phase transition of LC
      revealed by SS 2D spectroscopy in the specific spectral regions of 1750-1650 and
      3000-2700 cm(-1) is in a good agreement with that revealed by DSC for the heating
      process. The VV 2D correlation spectroscopy analysis has provided information
      about the structural variations of inter-molecular hydrogen bonds. The different
      species of hydrogen-bonded and free -COOH and -COO- groups in the LC have been
      clarified by the VV 2D correlation analysis. It has also elucidated the specific
      order of the temperature-induced structural changes in the intra- and inter
      molecular hydrogen bonds concerning with the -COOH and/or -COO- groups in the LC.

PMID- 15248969
TI  - Vibrational frequencies and structural determination of triethynylmethylsilane.
AB  - The normal mode frequencies and corresponding vibrational assignments of
      Triethynylmethylsilane (CH3Si(CCH)3) are examined theoretically using the
      Gaussian98 set of quantum chemistry codes. Each of the vibrational modes was
      assigned to one of nine types of motion predicted by a group theoretical analysis
      (Si-C stretch, C triple bond C stretch, C-H stretch, C triple bond C-H bend, Si-C
      triple bond C bend, C-Si-C bend, H-C-H bend, CH3 wag, and CH3 twist) utilizing
      the C3v symmetry of the molecule. A set of uniform scaling factors was derived
      for each type of motion. Predicted infrared and Raman intensities are reported.

PMID- 15248971
TI  - Excitation wavelength dependent surface-enhanced Raman spectra of a dipping film
      of azobenzene-containing long-chain fatty acid on a silver mirror.
AB  - Surface-enhanced Raman scattering (SERS) of dipping films of azobenzene
      containing long-chain fatty acids, nAmH (n=8, 12, m=3, 5), on silver mirrors
      measured with a wide range of excitation wavelengths in the 457.9-1064 nm region
      is reported. The obtained Raman spectra show great SERS effect even with the 1064
      nm excitation, and the excitation with 457.9, 476.5, and 488.0 nm gives surface
      enhanced resonance Raman scattering (SERRS) due to the resonance effect of the
      symmetry-forbidden n-pi* transition of the azo group. Of particular note in the
      present study is that the SERS spectra with the excitation in the 532-1064 nm
      region yield Raman bands whose frequencies are almost identical to those bands in
      Raman spectra of nAmH in solid state while the SERRS spectra with the excitation
      in the 457.9-514.5 nm region show not only a set of bands which correspond to
      those of nAmH in the solid state but also a set of bands whose frequencies show a
      significant shift from those of the bands of nAmH in the solid state. These
      observations lead us to conclude that there are two kinds of molecular aggregates
      in the dipping films of azobenzene-containing long-chain fatty acid in which
      azobenzene moieties are condensed to form small bundles.

PMID- 15248972
TI  - A theoretical study of P4O10: vibrational analysis, infrared and Raman spectra.
AB  - The normal mode frequencies and the corresponding vibrational assignments of
      tetraphosphorus decaoxide (P4O10) in tetrahedral (Td) symmetry are examined
      theoretically and experimentally. The Gaussian 98 set of quantum chemistry codes
      at the HF/6-311G*, MP2/6-311G*, and DFT/B3LYP/6-311G* levels of theory are used.
      By comparison to experimental normal mode frequencies deduced by Gilliam et al.
      [J. Phys. Chem. B 107 (2003) 2892], Chapman [Spectrochim. Acta A, 24 (1968)
      1687], Beattie et al. [J. Chem. Soc. A (1970) 449], Konings et al. [J. Mol.
      Spectrosc. 152 (1992) 29] and the present work, correction factors for
      predominant vibrational motions are determined and compared. Normal modes were
      decomposed into five non-redundant motions (P-O stretch, P=O stretch, P-O-P bend,
      P-O-P wag, and P=O wag). Standard deviations found for the HF, MP2, and DFT
      corrected frequencies compared to experiment are 9, 5, and 4 cm(-1),
      respectively. Electron distribution for selected molecular orbitals is
      considered.

PMID- 15248973
TI  - Primary electron-transfer dynamics in 2-phenylindole-9-cyanoanthracene system. A
      comparative study with 2-methylindole.
AB  - Electrochemical measurements by cyclic voltammetry predict the possibility of
      occurrence of photoinduced electron-transfer (PET) reactions between the ground
      state of 2-phenylindole (2PI) (electron donor) and the excited singlet of 9
      cyanoanthracene (9CNA) molecule acting as an electron acceptor. However, 2PI
      should be expected to behave as a relatively weaker electron donating agent than
      the structurally related donor 2-methylindole (2MI) as it possesses higher
      oxidation potential value. Both steady-state and time-resolved spectroscopic
      measurements in the polar acetonitrile (ACN) and ethanol (EtOH) solvents show
      that the fluorescence quenching phenomenon of 9CNA in presence of 2PI is
      primarily due to the involvement of dynamic process which in high probability
      should be PET. Nevertheless, in less polar tetrahydrofuran (THF) medium, the
      quenching of 9CNA results from the combined effect of dynamic and static modes.
      The transient absorption spectra, measured by using nanosecond laser flash
      photolysis, of 9CNA in presence of 2PI exhibit the signature of the bands of the
      anionic species of 9CNA, cation of the donor 2PI and the contact neutral radical.
      Observations of the transient absorption at the different delays infer that ion
      recombination mechanism is responsible for production of the monomeric triplets
      of both 9CNA and 2PI. From the transient absorption decays in ACN medium, it has
      been demonstrated that the diffusional separation of ions from geminate ion-pair
      is facilitated in the case of 2MI-9CNA pair whereas for 2PI-9CNA system the
      energy wasting charge recombination dominates over the process of charge
      dissociation. From the above observations, the possibility of developing much
      potential photosynthetic model compounds with the donor 2MI, rather than with the
      other donor 2PI molecule has been hinted.

PMID- 15248974
TI  - Experimental and theoretical studies of the vibrational spectra of cis-1-bromo-2
      fluoroethene.
AB  - The gas-phase infrared spectrum of cis-1-bromo-2-fluoroethene has been studied at
      low resolution in the range 200-6500 cm(-1), leading to a complete assignment of
      the fundamentals, except the lowest vibrational mode nu9 predicted at 167 cm(-1).
      The remaining vibrational structure has been mainly interpreted in terms of first
      overtone or two quanta combination bands. Isotopic (79/91)Br shift has been
      observed only in the nu8 fundamental. The equilibrium structure and the quadratic
      force field have been investigated theoretically at CCSD(T) level of theory
      employing Dunning's correlation consistent triple-zeta basis set. Cubic and
      semidiagonal quartic force field have been calculated using second-order Moller
      Plesset perturbation theory and Ahlrich' split valence (SV) contracted basis set.
      After a minor scaled quantum mechanical (SQM) adjustment of the quadratic force
      constants, the vibrational analysis, based on the second-order perturbation
      theory, has been carried out with the calculated force constants.

PMID- 15248976
TI  - Effects of solvent on the fluorescence of 2-anilinonaphthalene.
AB  - Solvation dynamics of 2-anilinonaphthalene (2-AN) has been studied at room
      temperature in a series of solvents with different polarity. The computation at
      the Hartree-Fock level of theory with the 3-21G* basis set has also been
      performed to study the structure of 2-AN in the ground and excited states. Steady
      state fluorescence and fluorescence lifetime of 2-AN show the dependence of the
      fluorescence decay on the polarity and viscosity of solvent.

PMID- 15248975
TI  - Roughened silver electrodes for use in metal-enhanced fluorescence.
AB  - Roughened silver electrodes are widely used for surface-enhanced Raman scattering
      (SERS). We tested roughened silver electrodes for metal-enhanced fluorescence.
      Constant current between two silver electrodes in pure water resulted in the
      growth of fractal-like structures on the cathode. This electrode was coated with
      a monolayer of human serum albumin (HSA) protein that had been labeled with a
      fluorescent dye, indocyanine green (ICG). The fluorescence intensity of ICG-HSA
      on the roughened electrode increased by approximately 50-fold relative to the
      unroughened electrode, which was essentially non-fluorescent and increased
      typically two-fold as compared to the silver anode. No fractal-like structures
      were observed on the anode. Lifetime measurements showed that at least part of
      the increased intensity was due to an increased radiative decay rate of ICG. In
      our opinion, the use of in situ generated roughened silver electrodes will find
      multifarious applications in analytical chemistry, such as in fluorescence based
      assays, in an analogous manner to the now widespread use of SERS. To the best of
      our knowledge this is the first report of roughened silver electrodes for metal
      enhanced fluorescence.

PMID- 15248977
TI  - Theoretical investigations of the EPR g factors and the local structure for Er3+
      in BaWO4.
AB  - The electron paramagnetic resonance (EPR) parameters g factors g(parallel) and
      g(perpendicular) as well as the local structure for Er3+ in scheelite-type BaWO4
      are theoretically investigated by using the perturbation formulas of the EPR
      parameters for a 4f11 ion under tetragonal symmetry. In these formulas, the
      contributions to the EPR parameters arising from the second-order perturbation
      terms and the admixture of different states are included. It is found that the
      impurity-ligand bonding angles (or the polar angles) related to the fourfold axis
      in the tetragonal Er3+ center are about 1.5 degrees smaller than those in pure
      crystal. The calculated EPR parameters are in agreement with the observed values.
      The validity of the results is discussed.

PMID- 15248978
TI  - Quantum-chemical study of the structure of the acetyl fluoride molecule in the
      ground and lowest excited singlet and triplet electronic states.
AB  - The structure of the conformationally flexible acetyl fluoride molecule (CH3CFO
      and CD3CFO) in the ground (S0) and lowest excited triplet (T1) and singlet (S1)
      electronic states was calculated by different quantum-chemical methods (RHF, UHF,
      MP2, CASSCF). The equilibrium geometric parameters and harmonic vibrational
      frequencies of the molecules in these electronic states were estimated. The
      calculations demonstrated that the electronic excitation causes considerable
      conformational changes involving the rotation of the CH3(CD3) top and a
      substantial deviation of the CCFO carbonyl fragment from planarity. For large
      amplitude vibrations, namely, for the torsional vibration in the S0 state and the
      torsional and inversion (nonplanar carbonyl fragment) vibrations in the T1 and S1
      states, the quantum-mechanical problems were solved in one-dimensional (1D) and
      two-dimensional (2D) approximations. The results of calculations are in good
      agreement with experimental data.

PMID- 15248979
TI  - Absorption and fluorescent spectral studies of imidazophenazine derivatives.
AB  - Absorption and fluorescent spectra as well as fluorescence polarization degree of
      imidazo-[4,5-d]-phenazine (F1) and its two modified derivatives, 2
      trifluoridemethylimidazo-[4,5-d]-phenazine (F2) and 1,2,3-triazole-[4,5-d]
      phenazine (F3), were investigated in organic solvents of various polarities and
      hydrogen bonding abilities. Extinction coefficients of F2 and F3 are increased,
      their fluorescence Stokes shifts are reduced in comparison with those for
      unmodified imidazophenazine. For F3 a red shift of the longwave absorption band
      is observed by 15-20 nm. Modifications of imidazophenazine have led to a
      sufficient increase of fluorescence polarization degrees that enables to use F2
      and F3 as promising fluorescent probes with polarization method application. The
      configuration, atomic charge distribution and dipole moments of the isolated dye
      molecules in the ground state were calculated by the DFT method. The computation
      has revealed that ground state dipole moments of F1, F2, and F3 differ slightly
      and are equal to 3.5, 3.2, and 3.7D, respectively. The changes in dipole moments
      upon the optical excitation for all derivatives estimated using Lippert equation
      were found to be Deltamu = 9 D. The energies of the electronic S1<--S0 transition
      in solvents of different proton donor abilities were determined, and energetic
      diagram illustrating the substituent effect was plotted. For nucleoside analogs
      of these compounds, covalently incorporated into a nucleotide chain, we have
      considered a possibility to use them as fluorescent reporters of hybridization of
      antisense oligonucleotides, as well as molecular anchors for its stabilization.

PMID- 15248980
TI  - IR spectral and structural changes caused by the conversion of 3-methoxy-4
      hydroxybenzaldehyde (vanillin) into the oxyanion.
AB  - The spectral and structural changes, caused by the conversion of the vanillin
      molecule into the corresponding oxyanion have been studied by IR spectra and
      normal coordinate calculations within the Onsager self-consistent reaction field
      (SCRF) model, using a density functional theory (DFT) method at the Becke3LYP/6
      31+G** level. Structures of all conformational isomers of vanillin and of its
      anion have been located, as well as their total and relative energies have been
      determined. The conversion leads to geometry changes in the whole species, due to
      the strong O-/acceptor polar resonance through the para phenylene ring. The
      conversion causes a 41 cm(-1) decrease in the frequency of the carbonyl
      stretching band nu(C=O), strong intensity increases (1.6 - 7.2-fold) of the
      aromatic skeletal nu8 and nu19 as well as formyl nu(CH) bands. According to the
      calculations the oxyanionic charge is delocalized over aldehyde group (0.25 e-),
      phenylene ring (0.13 e-), methoxy group (0.07 e-) and oxyanyonic center (0.55 e
      ).

PMID- 15248981
TI  - Raman, SERS and theoretical studies of papaverine hydrochloride and its neutral
      species.
AB  - Density functional theory (DFT) calculations and an experimental vibrational
      characterization of papaverine hydrochloride were performed. The computed
      structural parameters agree very well with the experimental values of the related
      crystal structure. The pH dependent Raman and SERS spectra of papaverine
      hydrochloride were recorded and discussed with the assistance of our theoretical
      results (harmonical vibrational wavenumbers, Raman scattering activities, total
      electron density and Natural Population Analysis of the molecule) and the SERS
      surface selection rules. Two different adsorption geometries were found for the
      corresponding evidenced species of papaverine, protonated and neutral,
      respectively.

PMID- 15248982
TI  - Stratified response to environmental stress in a polar lichen characterized with
      FT-Raman microscopic analysis.
AB  - The role of Antarctic epilithic lichens in the primary colonization of rocks and
      in the formation of soils is receiving attention because of the production of the
      stress-protective biochemicals needed to combat radiation, desiccation and
      extremes of temperature. Raman microscopy has been used here to study the
      encrustations produced at the interface between the rock substratum and Buellia
      spp. lichen thalli; in addition to whewellite, calcium oxalate monohydrate, the
      presence of weddellite, the metastable dihydrate form, was confirmed in the
      encrustations. An unusual pigmentation of the rock surface found on detachment of
      the lichen growths is identified as beta-carotene from its characteristic Raman
      bands at 1525, 1191, 1157 and 1003 cm(-1); normally, beta-carotene, which has
      been identified as a UV-radiation protectant, is found at the exposed upper
      surface of the biological organism. The interface between the detached lichen
      thalli and the rock also contains whewellite as the sole biomineralization
      product--which suggests a possible strategy for the formulation of weddelite in
      the growing Buellia spp. colony as an anti-desiccant.

PMID- 15248983
TI  - The influence of the Tbeta level upon fluorescence and laser properties of
      aromatic compounds.
AB  - The fluorescence and laser properties of seven specially chosen aromatic
      compounds are studied at 293 degrees C. The quantum yield of fluorescence, gamma,
      decay times, tauf, of the deaerated and non-deaerated solutions are measured. The
      oscillator strength, fe, fluorescence rate constants, kf, natural lifetimes,
      tauT0, and intersystem crossing rate constants, kST, are calculated. Some laser
      parameters are calculated or measured experimentally. It is found that the
      position of the Tbeta level plays an important role in the fluorescence and laser
      properties of aromatic compounds. If the Tbeta level is situated below the Sp
      level, it decreases the quantum yield of fluorescence and the decay time and
      increases the threshold of laser action. If, due to some structural changes of a
      molecule, the Tbeta level is situated higher than the Sp level, then the quantum
      yield of fluorescence and the decay times are increasing and the threshold of
      laser action is decreasing. Such influence of the position of the Tbeta level
      upon fluorescence and laser properties of aromatic compound is explained by the
      fact that the Sp level mixes with the Tbeta level more readily than with other
      taupipi* levels.

PMID- 15248984
TI  - [Vibrational spectra of monoclinic diphosphates of formula AMP2O7].
AB  - The monoclinic pyrophosphates with AMP2O7 formula were synthesized. Their
      infrared and Raman spectra have been reported and analysed. The results of a
      force field calculation for CaCuP2O7 are presented.

PMID- 15248985
TI  - Highly selective spectrophotometric flow-injection determination of trace amounts
      of bromide by catalytic effect on the oxidation of m-cresolsulfonephthalein by
      periodate.
AB  - A new flow-injection method is reported for the determination of bromide. The
      method is based on catalytic effect of bromide on the oxidation of m
      cresolsulfonephthalein by periodate in acidic media. The reaction was followed
      spectrophotometrically by measuring the decrease in absorbance at 528 nm. The
      influence of pH, reagent concentration and manifold variables on the sensitivity
      was studied. Under optimum conditions, a calibration graph was obtained in the
      range of 0.160-20.00 microg ml(-1) bromides with a limit of detection of 0.150
      microg ml(-1) bromide. The relative standard deviation for ten replicate
      measurement of 1.0 microg ml(-1) bromide was 2.1%. The influence of potential
      interfering ions on the selectivity was studied. The method successes to measure
      bromide in the presence of other halide ions. The method was used to measure
      bromide in river water and tap water.

PMID- 15248986
TI  - Nile Blue in Triton-X 100/benzene-hexane reverse micelles: a fluorescence
      spectroscopic study.
AB  - We report the observation of ground state prototropic equilibrium of the dye Nile
      Blue in Triton-X 100/benzene-hexane reverse micellar system. In the absence of
      water, the deprotonated form of the dye is predominant. Addition of water
      produces the protonated form. At highest water loading, the equilibrium is still
      shifted towards the deprotonated form as revealed by the absorption spectrum. In
      neat Triton-X 100 also, the dye is present almost predominantly in the
      deprotonated form as revealed by the absorption spectrum. The average
      fluorescence lifetime of the dye is greater in neat Triton-X 100 than in Triton-X
      100 reverse micelles, when no water is added. Addition of water to the reverse
      micelles increases the average lifetime of the deprotonated species. We offer
      possible explanations to the above observations by discussing the structure and
      properties of the Triton-X 100/benzene-hexane reverse micelles.

PMID- 15248987
TI  - Study of lanthanide complexes with salicylic acid by photoacoustic and
      fluorescence spectroscopy.
AB  - Solid complexes Ln(Sal)3.H2O (Sal: salicylic acid; Ln: La3+, Nd3+, Eu3+, Tb3+)
      are synthesized, and their photoacoustic (PA) spectra in the UV-Vis region have
      been recorded. PA intensities of central lanthanide ions are interpreted in terms
      of the probability of nonradiative transitions. It is found that PA intensity of
      the ligand increases in the order of Tb(Sal)3.H2O < La(Sal3).H2O < Eu(Sal)3.H2O <
      Nd(Sal)3.H2O. Different PA intensities of the ligand are interpreted by
      comparison with the fluorescence spectra. Ternary complexes Eu(Sal)3Phen and
      Tb(Sal)3Phen (Phen: 1,10-phenanthroline) are synthesized. Compared with their
      binary complexes, PA intensity of the ligand Sal decreases for Eu(Sal)3Phen,
      while the reverse is true for that of Tb(Sal)3Phen. The luminescence of Eu3+
      increases remarkably when Phen is introduced, and luminescence of Tb3+ decreases
      greatly when Phen is added. The intramolecular energy transfer and relaxation
      processes in the complexes are discussed from two aspects: radiative and
      nonradiative relaxations.

PMID- 15248988
TI  - Raman spectroscopy of some basic chloride containing minerals of lead and copper.
AB  - Raman spectroscopy has been used to characterise several lead and mixed cationic
      lead minerals including mendipite, perite, laurionite, diaboleite, boleite,
      pseudoboleite, chloroxiphite, and cumengeite. Raman spectroscopy enables their
      vibrational spectra to be compared. The low wavenumber region is characterised by
      the bands assigned to cation-chloride stretching and bending modes. Phosgenite is
      a mixed chloride-carbonate mineral and a comparison is made with the molecular
      structure of the aforementioned minerals. Each mineral shows different hydroxyl
      stretching vibrational patterns, but some similarity exists in the Raman spectra
      of the hydroxyl deformation modes. Raman spectroscopy lends itself to the study
      of these types of minerals in complex mineral systems involving secondary mineral
      formation.

PMID- 15248989
TI  - Simulation of emission molecular spectra by a semi-automatic programme package:
      the case of C2 and CN diatomic molecules emitting during laser ablation of a
      graphite target in nitrogen environment.
AB  - Some emission spectra of diatomic molecules were calculated by a semi-automatic
      programme package in order to infer the rotational and vibrational temperatures
      in Boltzmann distribution by comparing them with the corresponding experimental
      ones. The calculation procedure was applied in the case of CN radical and C2
      molecule whose optical emission spectra were recorded during pulsed excimer laser
      ablation of a graphite target in low-pressure nitrogen environment. Computed
      similar or dissimilar values of rotational and vibrational temperatures let to
      verify the existence or not of local thermodynamic equilibrium and to hypothesise
      the temporal range necessary to establish it in such experiments.

PMID- 15248990
TI  - 4f-4f absorption spectra and hypersensitivity in nine-coordinate Ho(III) and
      Er(III) complexes in different environments.
AB  - The effect of change in the environment upon 4f-4f absorption spectra of nine
      coordinate Ho(III) and Er(III) complexes with thiocyanate and 2,2'-bipyridyl in
      methanol, DMSO, DMF and pyridine have been investigated. The oscillator strength
      for hypersensitive and non-hypersensitive transitions have been calculated and
      variation in the intensity and band shape with respect to solvent type is
      rationalized in terms of solvent structure and coordinating properties. A
      comparison with 1,10-phenanthroline complexes is investigated and has been found
      that phen has a larger impact on the transition intensities for these ions.
      Pyridine has been found most effective in promoting 4f-4f intensity. The results
      indicate that it is important to consider both the static and dynamic coupling
      mechanism while analysing the oscillator strength of hypersensitive transition.

PMID- 15248991
TI  - Studies on the molecular interaction of phenazine dyes with Triton X-100.
AB  - The absorption spectra of phenazine dyes such as phenosafranin (PSF), safranin-O
      (Saf-O), and safranin-T (Saf-T) in aqueous solution of Triton X-100 (TX-100) show
      that phenazine dyes form 1:1 charge-transfer (CT) or electron-donor-acceptor
      (EDA) complex with TX-100. The photogalvanic and photoconductivity studies also
      support the above interaction. From the thermodynamic, spectrophotometric and
      photophysical parameters of these complexes, the abilities of dyes to accept
      electron are found to be in the order: PSF > Saf-O > Saf-T. There is a good
      correlation among the spectral and thermodynamic properties of these complexes.

PMID- 15248992
TI  - Structural and solvent dependence of superexciplex.
AB  - In this paper, we show that a few coumarin dye solutions exhibit dual amplified
      spontaneous emission (ASE) spectra under pulsed laser excitation, though all
      these solutions exhibit only one fluorescence band under steady-state conditions.
      The anomalous band, appearing only in ASE spectra, had been attributed to the
      superexciplex--a new molecular species. This is made of two excited molecules and
      is obtainable only under pulsed laser excitation. This complex is different from
      the well known excimer or exciplex, wherein only one atom or molecule is in the
      excited state. The superexciplex is possible with the two polar excited molecules
      coming together to form an excited state association, with the solvent acting as
      some sort of bridge. With very polar dye molecules, such an association is
      possible even with the inert benzene acting as a bridge; otherwise solvents like
      ethyl acetate, with an oxygen atom, is necessary for the linkage.

PMID- 15248993
TI  - Rovibrational energy levels of hydrogen peroxide, studied by MULTIMODE with a
      reaction path Hamiltonian.
AB  - Recently, Carter and Handy [J. Chem. Phys. 113 (2000) 987] have introduced the
      theory of the reaction path Hamiltonian (RPH) [J. Chem. Phys. 72 (1980) 99] into
      the variational scheme MULTIMODE, for the calculation of the J=0 vibrational
      levels of polyatomic molecules, which have a single large-amplitude motion. In
      this theory the reaction path coordinate s becomes the fourth dimension of the
      moment-of-inertia tensor, and must be treated separately from the remaining 3N-7
      normal coordinates in the MULTIMODE program. In the modified program, complete
      integration is performed over s, and the M-mode MULTIMODE coupling approximation
      for the evaluation of the matrix elements applies only to the 3N-7 normal
      coordinates. In this paper the new algorithm is extended to the calculation of
      rotational-vibration energy levels (i.e. J>0) with the RPH, following from our
      analogous implementation for rigid molecules [Theoret. Chem. Acc. 100 (1998)
      191]. The full theory is given, and all extra terms have been included to give
      the exact kinetic energy operator. In order to validate the new code, we report
      studies on hydrogen peroxide (H2O2), where the reaction path is equivalent to
      torsional motion. H2O2 has previously been studied variationally using a valence
      coordinate Hamiltonian; complete agreement for calculated rovibrational levels is
      obtained between the previous results and those from the new code, using the
      identical potential surface. MULTIMODE is now able to calculate rovibrational
      levels for polyatomic molecules which have one large-amplitude motion.

PMID- 15248994
TI  - Vibrational spectra of 1-methylthymine: matrix isolation, solid state and
      theoretical studies.
AB  - The infrared spectra of 1-methylthymine (1-MeT) in argon and nitrogen cryogenic
      matrices are presented, for the first time. The molecular structure,
      conformations, vibrational frequencies, infrared intensities and Raman scattering
      activities of 1-MeT have been calculated by the DFT(B3LYP), MP2 and HF methods
      using the D95V** basis set. The theoretically predicted intensity pattern of the
      IR and Raman bands has proved to be of great help in assigning the experimental
      spectra. Rigorous normal coordinate analysis has been performed, at each level of
      theory. The unequivocal and complete vibrational assignment for 1-MeT has been
      made on the basis of the calculated potential energy distribution (PED).
      Comparison of the experimental matrix isolation spectra with the theoretical
      results has revealed that the B3LYP method is superior to both the MP2 and HF
      methods in predicting the frequencies of uracil derivatives. The MP2 method
      consistently underestimates the frequencies of the out-of-plane gamma(C=O) and
      gamma(C-H) bending modes, while the HF method yields the reverse order of the
      frequencies of two nu(C=O) stretching vibrations. Investigation of the frequency
      shift of several bands, on passing from matrix isolation to solid state spectra,
      has provided information on the strength of intermolecular hydrogen bonding in
      the crystal of 1-MeT. Several ambiguities in the earlier assignments of the
      vibrational spectra of polycrystalline 1-MeT have been clarified.

PMID- 15248995
TI  - A simple method to extract spectral parameters using fractional derivative
      spectrometry.
AB  - The nonlinear fitting method, based on the ordinary least squares approach, is
      one of several methods that have been applied to fit experimental data into well
      known profiles and to estimate their spectral parameters. Besides linearization
      measurement errors, the main drawback of this approach is the high variance of
      the spectral parameters to be estimated. This is due to the overlapping of
      individual components, which leads to ambiguous fitting. In this paper, we
      propose a simple mathematical tool in terms of a fractional derivative (FD) to
      determine the overlapping band spectral parameters. This is possible because of
      several positive effects of FD connected with the behavior of its zero-crossing
      and maximal amplitude. For acquiring a stable and unbiased FD estimate, we
      utilize the statistical regularization method and the regularized iterative
      algorithm when a priori constraints on a sought derivative are available. Along
      with the well-known distributions such as Lorentzian, Gaussian and their linear
      combinations, the Tsallis distribution is used as a model to correctly assign
      overlapping bands. To demonstrate the power of the method, we estimate unresolved
      band spectral parameters of synthetic and experimental infra-red spectra.

PMID- 15248996
TI  - Single crystal EPR studies of an organic NLO material: methyl-p-hydroxy benzoate.
AB  - Single crystals of an organic nonlinear optical (NLO) material methyl-p-hydroxy
      benzoate (MHB) were grown by solvent evaporation technique. EPR spectra were
      recorded for Er3+: MHB and gamma-irradiated MHB at room temperature at X-band
      frequencies. The angular variation studies of the spectra were observed and the
      principal values of g were determined. The grown crystals were characterized by
      single crystal X-ray diffraction studies.

PMID- 15248997
TI  - Preparation and application of MS-M2+ nanoparticles as a novel resonance light
      scattering probe.
AB  - Metal-enriched metal sulfide nanoparticles (MS-M2+, M = Zn, Cu, Pb, Ni, Cd) have
      been prepared. We found ZnS-Zn2+ and CuS-Cu2+ nanoparticles are water-soluble and
      biocompatible. They could be used as new kind of resonance light-scattering (RLS)
      probes in the determination of gamma-globulin human, which was proved to be a
      simple, rapid and specific method. In comparison with organic dye probes, these
      nanoparticles probes are brighter, more stable against photobleaching, and do not
      suffer from blinking. Under the optimum conditions, the response is linearly
      proportional to the concentration of gamma-globulin human. ZnS-Zn2+ nanoparticles
      as a RLS probe: between 0.1 and 2.0 mg l(-1), and the limit of detection is
      0.0403 mg l(-1); CuS-Cu2+ nanoparticles as a RLS probe: between 0.1 and 1.5 mg l(
      1), and the limit of detection is 0.0646 mg l(-1). We find the effect of other
      protein on this assay is weak, this assay has good selectivity.

PMID- 15248998
TI  - Vibrational frequencies and structural determination of tetraiododiphosphine.
AB  - The normal mode frequencies and corresponding vibrational assignments of of
      tetraiododiphosphine in C2h symmetry are examined theoretically using the
      Gaussian 98 set of quantum chemistry codes. All normal modes were successfully
      assigned to one of six types of motion (P-I stretch, P-P stretch, PI2 scissors,
      PI2 twist, PI2 wag, and PI2 rock) predicted by a group theoretical analysis.
      Computed vibrational frequencies are with IR and Raman spectra available in the
      literature, and uniform scaling factors are derived. Theoretical IR and Raman
      intensities are reported.

PMID- 15248999
TI  - Spectroscopic, redox and biological activities of transition metal complexes with
      ons donor macrocyclic ligand derived from semicarbazide and thiodiglycolic acid.
AB  - A novel macrocyclic Schiff base ligand (2,5,9,12,14,18-hexaoxo-7,16-dithia
      1,3,4,10,11,13-hexaazacycloocta-decane (H6L) with N4S2 coordinating sites was
      prepared by the reaction of the semicarbazide and thiodiglycolic acid. The
      transition metal complexes with macrocyclic ligand were synthesized and
      characterized by elemental analyses, magnetic susceptibility measurements, molar
      conductance, IR, electronic, and EPR spectral studies. Mass, 1H NMR and IR
      spectral techniques suggest the structural features of macrocyclic ligand.
      Magnetic and electronic spectral studies suggest an octahedral geometry of
      complexes. Electrochemical behaviour of cobalt, nickel and copper complexes were
      determined by cyclic voltammetry. The cyclic voltammogram of the copper complex
      at room temperature shows a quasi-reversible peaks for Cu(III)-->Cu(II) and
      Cu(II)-->Cu(I) couples. The macrocyclic ligand and its complexes show growth
      inhibitory activity against pathogenic bacteria and plant pathogenic fungi A.
      niger, A. alternata and P. variotii. Most of the complexes have higher activities
      than that of free ligand.

PMID- 15249000
TI  - Theoretical study of the structures, stability and vibrational spectra of the
      nitrous acid complexes with CH4.
AB  - The structures, stability and vibrational spectra of the binary complexes
      CH4...HONO-trans and CH4...HONO-cis have been investigated using ab initio
      calculations at the SCF and MP2 levels with 6-311++G(d,p) basis set and B3LYP
      calculations with 6-31G(d,p) and 6-31+G(d,p) basis sets. Full geometry
      optimization was made for the complexes studied. It was established that the
      complex CH4...HONO-trans is more stable by 0.41 kcal mol(-1) than the complex
      CH4...HONO-cis. The accuracy of the ab initio calculations have been estimated by
      comparison between the predicted values of the vibrational characteristics
      (vibrational frequencies and infrared intensities) and the available experimental
      data. It was established, that the methods, used in this study are well adapted
      to the problem under examination. The predicted values with the B3LYP
      calculations are very near to the results, obtained with 6-311++G(d,p)/MP2. The
      changes in the vibrational characteristics of methane and trans-, cis-nitrous
      acid upon formation of the hydrogen bond show that the complexes CH4...HONO-trans
      and CH4...HONO-cis have geometry in which the OH group interacts with a methane
      molecule forming a single hydrogen bond. This fact is confirmed by relatively
      strong perturbation of the OH stretching vibration to lower frequencies and an
      increase of the infrared intensity of this vibration up to three times upon
      hydrogen bonding.

PMID- 15249001
TI  - Fourier transform infrared and Raman spectra. Semi empirical AM1 and PM3; MP2/DZV
      and DFT/B3LYP-6-31G(d) ab initio calculations for dimethylterephthalate (DMT).
AB  - Fourier transform infrared and Raman spectra of dimethylterephthalate (DMT), as
      microcrystalline powder, have been investigated. The vibrational spectra were
      calculated using the AM1 and PM3 semi empirical procedures, and the Moller
      Plesset (MP2/DZV), and the Becke-Lee, Yang and Parr gradient-corrected
      correlation functional: B3LYP/6-31G(d) ab initio calculations. On this basis, and
      assisted with the FT-IR and Raman spectra of the terephthalic acid, an assignment
      of the vibrational spectra of dimethylterephthalate was proposed. In the
      calculations, remarkable differences concerning the assignments of the
      vibrational spectra were noted between the AM1 and PM3 methods. Also, the ab
      initio procedure shows differences in interpreting the spectra compared with the
      semi empiric procedures, and among themselves. Calculated geometrical parameters
      were compared with the experimental values of dimethylterephthalate,
      diethylterephthalate and terephthalic acid.

PMID- 15249002
TI  - Spectroscopic studies of the reaction of iodine with 2,3-diaminopyridine.
AB  - The charge-transfer interaction of 2,3-diaminopyridine (DAPY) and iodine has been
      investigated spectrophotometrically in the solvents chloroform and
      dichloromethane at room temperature. The results indicate the formation of 1:2
      charge-transfer complex in each solvent with the observation of the two
      characteristic absorptions for triiodide ion around 355 and 295 nm. The iodine
      complex is formulated as [(DAPY)I]+.I3-. The formation of the triiodide ion, I3-,
      is further confirmed by the observation of the characteristic bands for non
      linear I3- ion with C2v symmetry at 151 and 132 cm(-1) assigned to nu(as)(I-I)
      and nu(s)(I-I) of the I-I bonds and at 61 cm(-1) due to bending delta(I3-). The
      mid infrared spectra of (DAPY) and triiodide complex are also obtained and
      assigned.

PMID- 15249003
TI  - Ground-state potential energy function of SiCl+.
AB  - Vibration-rotational (infrared) spectra belonging to four isotopomers of SiCl+
      molecular ion in the ground X1Sigma+ electronic state (in total 152 transitions
      of the fundamental and hot bands up to nu=6) have been reduced to the parameters
      of the Born-Oppenheimer potential, which is represented in the form of the
      generalized potential energy function. The dimensionless standard error of the
      fit is 0.95. The obtained potential is most accurate presently available.

PMID- 15249004
TI  - The analysis of the zero-order and the second derivative spectra of retinol
      acetate, tocopherol acetate and coenzyme Q10 and estimation of their analytical
      usefulness for their simultaneous determination in synthetic mixtures and
      pharmaceuticals.
AB  - The aim of the present work was to develop a simple and rapid method of retinol
      acetate, tocopherol acetate and coenzyme Q(10) determination in pharmaceuticals
      without involving any preparation operations like separation or masking. The
      values of second derivative amplitude at 212 nm for tocopherol, 351 nm for
      retinol and 222 nm for coenzyme were used for construction of calibration graphs.
      Beer's law is obeyed in the concentration range 0.5-20, 0.5-7.5 and 0.5-30 microg
      ml(-1) for retinol acetate, tocopherol acetate and coenzyme, respectively. The
      elaborated procedures were successfully applied to the simultaneous determination
      of studied compounds in their binary synthetic mixtures and in commercial
      preparations with high reliability and repeatability. Spectral properties of
      retinol acetate allows to determine its contents in ternary mixture which
      includes Vitamin E and coenzyme Q(10).

PMID- 15249005
TI  - Towards clarifying the N-M vibrational nature of metallo-phthalocyanines.
      Infrared spectrum of phthalocyanine magnesium complex: density functional
      calculations.
AB  - Infrared frequencies and intensities for the magnesium phthalocyanine complex
      MgPc have been calculated at density functional B3LYP level using the 6-31G(d)
      basis set. Detailed assignments of the metal-nitrogen (N-M) vibrational bands in
      the IR spectrum have been made on the basis of comparison of the calculated data
      of MgPc with the experimental result and also with that of H(2)Pc. The empirical
      controversial assignment of the characteristic band at 886-919 cm(-1) for metallo
      phthalocyanines is also clearly interpreted. Nevertheless, the previous
      assignments of N-H stretchings, in-plane bending (IPB) and out-of-plane bending
      (OPB) modes made based on the comparative calculation of H(2)Pc and D(2)Pc are
      confirmed again by the present research result.

PMID- 15249006
TI  - X-band electron paramagnetic resonance, optical spectra and some biological (SOD
      and antimicrobial activity) studies of the copper(II) complexes: a plausible
      model for superoxide dismutase.
AB  - The synthesis and characterization of homobinuclear complex by 2-ethylimidazole
      is reported along with two mononuclear complexes. Magnetic measurements and
      electron parameter resonance (e.p.r.) spectroscopy of the homobinuclear complex
      have shown an antiferromagnetic exchange interaction. Superoxide dismutase and
      antimicrobial activities of these complexes have also been measured.

PMID- 15249007
TI  - Spectroscopic characterization of intramolecular charge transfer of sodium 4-(N,N
      dimethylamino)naphthalene-1-sulfonate.
AB  - In this paper, a new dual fluorescent N,N-dimethylaminonaphthalene derivative,
      sodium 4-(N,N-dimethylamino)naphthalene-1-sulfonate (SDMDNS), was reported. It
      was found that SDMDNS emits dual fluorescence only in highly polar solvent water
      but not in organic solvents such as methanol, dioxane and acetonitrile. Only a
      single broad band emission at ca. 420 nm was observed in the short wavelength
      region in organic solvents. The dual fluorescence of SDMDNS in water was found at
      423 and 520 nm, respectively. Introduction of organic solvent as ethanol into
      aqueous solution of SDMDNS leads to blue shift of the long-wavelength emission,
      and this was evidently supported by introduction of cyclodextrin or surfactant in
      the aqueous solution. It indicates that a highly polar solvent was required to
      bring out dual fluorescence; furthermore, the short wavelength fluorescence is
      emitted from locally excited (LE) state and the long wavelength fluorescence is
      emitted from charge transfer (CT) state. The pH dependence of the dual
      fluorescence of SDMDNS demonstrates that the neutral form of the molecular has a
      higher ratio of CT band intensity to LE band. Temperature effect on the excited
      state of SDMDNS was also examined and gave stabilization enthalpy (-DeltaH ) of
      the CT reaction 8.7 kJ mol(-1).

PMID- 15249008
TI  - Synthesis, characterization and electronic spectra of cefadroxil complexes of d
      block elements.
AB  - Cefadroxil (CD) is an essential pharmaceutical drug used in curing many diseases.
      Due to its popular use in many pharmaceutical forms, attention is paid in this
      research to the synthesis and stereochemistry of new iron, cobalt, nickel,
      copper, and zinc complexes of this drug both in solution and the solid states.
      The spectra of these complexes in solution and the study of their stoichiometry
      refer to the formation of 1:1 and 1:2 ratios of metal (M) to ligand (L). The
      calculated stability constants (Kf) of these complexes (1.5x10(7) to 5x10(13))
      and the change in free energy of formation (deltaGf=2.5-12.5 kcal mol(-1) degree(
      1)) are indicative of their high stability. The stereo chemical structure of the
      solid complexes was studied on the basis of their analytical, spectroscopic,
      magnetic, and thermal data. Infrared spectra proved the presence of M-N and M-O
      bonds. Magnetic susceptibility and solid reflectance spectral measurements were
      used to infer the structure. The prepared complexes were found to have the
      general formulae [ML(OH)x(H2O)y](H2O)z-M: Fe(II), x=0, y=2, z=1; M: Fe(III) and
      Co(III), x=1, y=2, z=1; M: Co(II) and Zn(II), x=0, y=1, z=0; M: Ni(II) and
      Cu(II), x=1, y=0, z=1; L: CD. Octahedral and tetrahedral structures were proposed
      for these complexes depending upon the magnetic and reflectance data and were
      confirmed by detailed mass and thermal analyses comparative studies.

PMID- 15249009
TI  - Quantitative NIR Raman analysis in liquid mixtures.
AB  - The capability to obtain quantitative information of a simple way from Raman
      spectra is a subject of considerable interest. In this work, this is demonstrated
      for mixtures of ethanol with water and rhodamine-6G (R-6G) with methanol, which
      were analyzed directly in glass vessel. The Raman intensities and a simple
      mathematical model have been used and applied for the analysis of liquid samples.
      It is starting point to generate a general expression, from the experimental
      spectra, as the sum of the particular expression for each pure compound allow us
      to obtain an expression for the mixtures which can be used for determining
      concentrations, from the Raman spectrum, of the mixture.

PMID- 15249010
TI  - Quantitative NIR-Raman analysis of methyl-parathion pesticide microdroplets on
      aluminum substrates.
AB  - The potential of Raman spectroscopy in the quantitative analysis of dilute
      organic contaminants on aluminum substrates is evidenced in this work. Methyl
      parathion microdroplets, an organophosphorus pesticide, has been used as a probe
      for this purpose. The samples were analyzed on an aluminum foil, which is very
      easy to acquire and to adapt. Moreover, aluminum foil does not need a previous
      treatment. Linear and no-linear curves as a function of the concentration of
      methyl-parathion versus the Raman intensity of the 1345 and 1110 cm(-1) peaks
      were established by means of a simple mathematical expression. A comparison with
      calibration curves fits very well, allowing quantification at concentration
      levels as low as parts per million.

PMID- 15249011
TI  - Structural and spectroscopic study of 5,7-dihydroxy-flavone and its complex with
      aluminum.
AB  - The structure, stability and molar absorptivity of the complex formed between
      AlCl(3) and 5,7-dihydroxy-flavone in methanol were investigated using UV-Vis
      spectroscopy and the AM1 method. The molar ratio method and Job's method of
      continuous variation were applied to ascertain the stoichiometric composition of
      the complex in methanol at constant ionic strength. A 1:2 complex was indicated
      by both methods. The molar absorptivity and stability constant of the complex
      were determined using a simple and accurate procedure that requires solutions
      having the ligand and metal ion in the stoichiometric proportion. The high
      stability constant demonstrates that the complexation reaction is total. The
      structure of this complex, obtained by the quantum semi-empirical AM1 method,
      indicates that two classes of metal-ligand interactions are involved in the
      formation of the metal complex: (a) two simple covalent bonds between the
      aluminum atom and the oxygen atoms of o-hydroxyl groups of 5,7-dihydroxy-flavone;
      (b) two stronger Coulombic interactions between the aluminum atom and the
      carbonyl oxygen atoms of the ligand.

PMID- 15249012
TI  - Influence of the crystal field stabilization energy of metal(II) ions on the
      structural distortion of matrix-isolated SO4(2-) guest ions in selenate matrices.
AB  - Infrared spectra of metal(II) selenate hydrates (MeSeO4.nH2O and
      Na2Me(SeO4)2.2H2O; n=6, 5, 4, 1; Me=Mg, Mn, Co, Ni, Cu, Zn, Cd) containing matrix
      isolated SO42- guest ions are reported and discussed with respect to the S-O
      stretching modes 3 and 1. An adequate measure for the SO42- guest ion distortion
      is the site group splitting deltanuas (deltanuab and deltanuac in the case of a
      doublet and a triplet for 3, respectively; a, being the highest wavenumbered
      component of nu3) and deltanumax (the difference between the highest and the
      lowest wave numbered S-O stretching modes). It has been shown that the SO42-
      guest ion distortion depends on both the number of the sulfate oxygen atoms
      involved in coordinative bonds with the metal(II) ions and the electronic
      configuration of the metal(II) ions, i.e. their crystal field stabilization
      energy (CFSE) additionally to the site symmetry and the local potential at the
      lattice site of the host lattice. The SO42- guest ions matrix-isolated in
      MeSeO4.H2O (Me=Mn, Co, Zn) and in Na2Me(SeO4)2.2H2O (Me=Mn, Cu, Cd) exhibit three
      bands corresponding to the nu3 modes as deduced from the site group analysis and
      deltanuab approximately equal to deltanubc. When SO42- guest ions are
      incorporated in the triclinic Na2Me(SeO4)2.2H2O host lattices (Me=Co, Ni, Zn) the
      nu3 stretching region resembles a higher local symmetry of the SO42- guest ions
      (an approximate (A1 + E) splitting) than the crystallographic one (i.e.
      deltanuab>deltanubc instead of deltanuab approximately equal to deltanubc) and,
      hence, the ratio deltanuab/deltanubc has to be taken into account (the higher
      value of the ratio deltanuab/deltanubc, the weaker is the distortion of the SO42-
      guest ions). The SO42- guest ions incorporated in MeSeO4.nH2O (n=6, 5, 4) exhibit
      a higher local symmetry of the guest ions than that deduced from the site group
      analysis (D2d for the SO42- guest ions in MeSeO4.5H2O, MeSeO4.4H2O and in the
      monoclinic MeSeO4.6H2O host lattices and close to Td in the tetragonal
      MeSeO4.6H2O host lattices). The analysis of the infrared spectra of selenate host
      lattices containing SO42- guest ions reveals that the guest ions are stronger
      distorted when the adjacent metal(II) ions have CFSE not equal to 0. These ions
      are more resistant to angular deformations of the MeO6-octahedra (i.e. changes in
      the O-Me-O bond angles), thus facilitating the SO42- guest ion distortion as
      compared to those having CFSE=0 which allow stronger angular deformations of the
      respective metal octahedra. Infrared spectra of kieserite-type compounds
      MeSeO4.H2O (Me=Mn, Co, Zn) containing matrix-isolated SO42- guest ions and Me'2+
      guest ions different from those of the host ions (i.e. Me'SO4.H2O in MeSeO4.H2O)
      are also presented and discussed (double matrix-spectroscopy).

PMID- 15249013
TI  - Preparations and spectroscopic studies of organotin complexes of diclofenac.
AB  - The reactions of the potent and widely used anti-inflammatory drug diclofenac,
      HL, with diorganotin(IV) oxides were studied. The dimeric tetraorganodistannoxane
      complexes [Me(2)LSnOSnLMe(2)](2), [Bu(2)LSnOSnLBu(2)](2), [Ph(2)LSnOSnLPh(2)](2)
      and the dibutyltin complex [Bu(2)SnL(2)], have been prepared and structurally
      characterized in the solid state by means of vibrational and 119Sn Mossbauer
      spectroscopy. Determination of lattice dynamics by temperature-dependent 119Sn
      Mossbauer spectroscopy. From the variable-temperature Mossbauer effect, the Debye
      temperature was determined. The complexes have been characterized in solution by
      NMR (1H and 13C) spectroscopy. Vibrational, Mossbauer, and NMR data are discussed
      in terms of the proposed structures.

PMID- 15249014
TI  - Spectroscopic study of chromium, iron, OH, fluid and mineral inclusions in
      uvarovite and fuchsite.
AB  - Octahedrally-coordinated Cr(3+) possesses peculiar spectral features which made
      easy to identify it in minerals, even in minor amounts. Chromium has been studied
      in uvarovite and fuchsite by optical and EPR spectra. Optical, EPR, FT-infrared
      and EPMA studies have also let to determine the presence of Fe(3+) and Ti(3+) and
      fluid inclusions within uvarovite and fuchsite. Absorption and scattering effects
      on the optical spectra obtained for Cr-bearing samples, resulting from the
      presence of inclusions, are also discussed in this work.

PMID- 15249015
TI  - Amino acid contents along the visual and equatorial axes of a pig lens by Raman
      spectroscopy.
AB  - Using near infrared Raman microspectroscopy with laser light of 830 nm, the
      distribution of amino acids along the visual and equatorial axes of a normal pig
      lens was studied. The classification of pig lens Raman spectra in these axes was
      performed using principal component analysis and linear discriminant analysis.
      The analysis of the scattered light selectively collected from point to point,
      along the visual axis, indicated that the tyrosine and tryptophan increases and
      then, at approximately 4 mm position, decreases. Moreover, in the equatorial
      plane, the nuclear part has the highest concentration of these amino acids.
      However, the phenylalanine content increases from anterior to posterior cortex of
      the lens as long as in the equatorial axis it slightly increases and then at
      approximately 2-2.3 mm position, decreases. The changes in amino acid
      conformation along the visual axis, similarly to the changes in protein
      conformation, may explain the refractive gradient of the lens.

PMID- 15249016
TI  - NIR vibrational overtone spectra of toluidines-evidence for steric and electronic
      effects in o-toluidine.
AB  - The near infrared vibrational overtone absorption spectra of liquid phase
      toluidines are reported. The analysis of the observed CH and NH local mode
      mechanical frequency values shows that there exists steric and electronic
      interaction between the amino and methyl groups in o-toluidine. This observation
      supports the conclusions drawn from structural studies of toluidines by resonance
      two-photon ionization (R2PI) spectroscopy, ab initio calculations and laser
      induced fluorescence studies reported earlier.

PMID- 15249017
TI  - CH overtone spectrum of nitromethane: a C3V coupled oscillator analysis using
      local mode parameters.
AB  - The near infrared overtone absorption spectrum of liquid phase nitromethane in
      the spectral region deltaV = 2-5 is reported. The observed spectrum is analysed
      using local mode model. It is shown that the observed CH local mode overtones and
      local-local combinations are well predicted by a C(3V) coupled oscillator
      Hamiltonian.

PMID- 15249018
TI  - New approach to IR study of monomer-dimer self-association: 2,2-dimethyl-3-ethyl
      3-pentanol in tetrachloroethylene as an example.
AB  - The dimerization of 2,2-dimethyl-3-ethyl-3-pentanol in tetrachloroethylene in the
      diluted region has been studied at four temperatures by IR spectroscopy. The
      aforementioned solute compound is chosen because self-association beyond
      dimerization is hampered by the steric hindrance generated by the bulky
      sidechains. The integrated absorbances of the monomer bands were treated based on
      Eq. (9) to obtain its molar absorptivity and dimerization constant. The same
      dimerization constant as well as the molar absorptivity of dimer band can be
      obtained based on Eq. (13) from the data treatment of the integrated absorbances
      of the dimer band. The disparity between two values of dimerization constant
      determined by two independent sources offers an opportunity to check the
      consistency of the determination. The standard enthalpy and entropy of
      dimerization have also been calculated by means of van't Hoff plot, respectively,
      from the data of temperature-dependent dimerization constants obtained from the
      monomer bands and dimer bands.

PMID- 15249019
TI  - Photophysical behaviour of 4-(imidazole-1-yl) phenol and its complexation with
      beta-cyclodextrin in ground and excited states.
AB  - This paper mainly dwells on photophysics of 4-(imidazole-1-yl) phenol (IDP) in
      different solvents and temperatures from the investigations of absorption,
      emission and laser flash photolysis and also on the nature of complexation with
      beta-cyclodextrin (CD) in ground and excited states. IDP makes 1:1 inclusion
      complex with beta-CD in ground, excited singlet and also in triplet states. The
      orientation of complex could be ascertained as imidazole moiety stays inside the
      cavity with phenol moiety stays in the bulk. A proposed energy level scheme
      unveils that vibronic interaction and spin-orbit interaction are found to be
      active differently in aprotic and protic solvents.

PMID- 15249020
TI  - The microstructures of biomineralized surfaces: a spectroscopic study on the
      exoskeletons of fresh water (Apple) snail, Pila globosa.
AB  - In view of the importance in understanding biomineralization processes in
      different molluskan species, the common fresh water apple snail Pila globosa in
      Indian origin was taken to explore its mineralized exoskeleton structures. The
      detailed structural studies of the exoskeletons of P. globosa have been
      undertaken. The isolated layers present in these shells were studied by electron
      paramagnetic resonance (EPR), optical absorption, and infrared spectral
      techniques. The EPR spectra of the organic protein layer periostracum show the
      characteristic signals corresponding to Fe(3+) ions at g = 4.1 and 2.0. The EPR
      spectra of the ostracum (middle) layer at room temperature gives a complicated
      spectrum consisting of a number of Mn(2+) signals of at least three sets due to
      the aragonite nature of the material. The results indicate the presence of the
      multivalent manganese ions, which undergo the redox mechanisms. The thermal
      variation of the EPR spectra show marked effect on these samples both in g-values
      and the basic spectral pattern.

PMID- 15249021
TI  - Acetylation of raw cotton for oil spill cleanup application: an FTIR and 13C MAS
      NMR spectroscopic investigation.
AB  - Fourier transform infrared (FTIR) and 13C MAS NMR spectroscopy have been used to
      investigate the acetylation of raw cotton samples with acetic anhydride without
      solvents in the presence of different amounts of 4-dimethylaminopyridine (DMAP)
      catalyst. This is a continuation of our previous investigation of acetylation of
      commercial cotton in an effort to develop hydrophobic, biodegradable, cellulosic
      sorbent materials for cleaning up oil spills. The FTIR data have again provided a
      clear evidence for successful acetylation. The NMR results further confirm the
      successful acetylation. The extent of acetylation was quantitatively determined
      using the weight percent gain (WPG) due to acetylation and by calculating the
      ratio R between the intensity of the acetyl C=O stretching band at 1740-1745 cm(
      1) and the intensity of C-O stretching vibration of the cellulose backbone at
      about 1020-1040 cm(-1). The FTIR technique was found to be highly sensitive and
      reliable for the determination of the extent of acetylation. The level of
      acetylation of the raw cotton samples was found to be much higher than that of
      cotton fabrics and the previously studied commercial cotton. The variation of the
      R and WPG with reaction time, amount of DMAP catalyst and different samples of
      raw cotton is discussed.

PMID- 15249022
TI  - Low temperature Fourier transform infrared spectra and hydrogen bonding in
      polycrystalline uracil and thymine.
AB  - The FTIR spectra of pure NH and isotopically diluted (NH/ND and ND/NH)
      polycrystalline uracil and thymine were measured in the range 4000-400 cm(-1) at
      temperatures from 300 to 10K. For the first time, the essentially narrow bands
      corresponding to the uncoupled stretching (nu(1)) and out of plane bending
      (nu(4)) NH proton modes of uracil and thymine were observed in the solid phase.
      It was found that in the nu(4) region the spectra reveal more details on the H
      bond interactions present in both solids than in the nu(1) range. The frequencies
      of the various bands observed in both spectral regions were used for estimation
      of the H-bond energy, using empirical correlations between this property and both
      the red shift of nu(1) and the blue shift of nu(4) that occur upon
      crystallization due to the establishment of the H-bonds. The results are compared
      with known thermodynamic, structural and theoretical data. The IR data also
      suggest that the H-bond networks of both crystals contain, besides the two
      NH...O=C bonds revealed by X-ray experiments, additional types of H-bonds, which
      do not show long range periodicity and, thus, cannot be detected by the
      conventional structural methods. The assignment of some other bands in the
      spectra of both substances was also reviewed.

PMID- 15249023
TI  - Liquid phase overtone spectral investigations of 2,6-dimethylaniline and 2,4
      dimethylaniline-evidence for steric nature of the ortho effect and the consequent
      base weakening.
AB  - The near infrared vibrational overtone absorption spectrum of liquid phase 2,6
      dimethylaniline and 2,4-dimethylaniline are reported in the region deltanu = 2, 3
      and 4. The aryl CH, methyl CH and NH local mode mechanical frequency values
      obtained from fitting the overtones are analysed and compared. The observation
      supports the conclusions drawn from earlier base strength studies on methylation
      of aniline and structural studies of toluidines by ab initio calculations. The
      introduction of the ortho methyl group into aniline weakens its base strength due
      to steric strain.

PMID- 15249024
TI  - Density functional theory and ab initio studies of geometry, electronic structure
      and vibrational spectra of novel benzothiazole and benzotriazole herbicides.
AB  - The ground-state geometries, electronic structures and vibrational wavenumbers of
      S-1,3-benzothiazolyl-4-bromobenzenecarbothioate and S-(5,7-dimethyl-3H-4lambda-5
      [1,2,4]triazolo[1,5-a]pyridinyl)4-chlorobenzenecarbothioate were studied by DFT
      B3LYP, BLYP and ab initio RHF method with different basis sets. The comparison
      was performed for optimized geometries, thermodynamic parameters and electronic
      structures at different levels of theory. Because of the larger repulsion effect
      in triazole ring, the vibrational wavenumbers of skeleton vibration of triazole
      ring are significantly lower than that of thiazole ring.

PMID- 15249025
TI  - The use of FTIR microscopy for evaluation of herpes viruses infection development
      kinetics.
AB  - The kinetics of Herpes simplex infection development was studied using an FTIR
      microscopy (FTIR-M) method. The family of herpes viruses includes several members
      like H. simplex types I and II (HSV I, II), Varicella zoster (VZV) viruses which
      are involved in various human and animal infections of different parts of the
      body. In our previous study, we found significant spectral differences between
      normal uninfected cells in cultures and cells infected with herpes viruses at
      early stages of the infection. In the present study, cells in cultures were
      infected with either HSV-I or VZV and at various times post-infection they were
      examined either by optical microscopy or by advanced FTIR-M. Spectroscopic
      measurements show a consistent decrease in the intensity of the carbohydrate peak
      in correlation with the viral infection development, observed by optical
      microscopy. This decrease in cellular carbohydrate level was used as indicator
      for herpes viruses infection kinetics. This parameter could be used as a basis
      for applying a spectroscopic method for the evaluation of herpes virus infection
      development. Our results show also that the development kinetics of viral
      infection has an exponential character for these viruses.

PMID- 15249026
TI  - 51V(n, beta)52Cr reaction for neutron dosimetry: development and assessment of a
      spectrophotometric method for determination of Cr in vanadium at sub ppm level.
AB  - With a view to monitoring the changes in coloration caused by the nuclear
      reaction 51V(n, beta)52Cr in solution of vanadyl sulphate and using it for
      neutron dosimetry, electronic absorption spectra of vanadyl sulphate solutions
      were investigated at different concentrations of chromate impurity in micromolar
      range. It was observed that the presence of chromate enhances the absorptivity
      over a wide wavelength range serving essentially as a colouring agent for
      vanadium matrix, presumably due to charge transfer process. The absorbance at 380
      nm varied linearly over a wide concentration range. The limit of detection of
      chromate obtained is shown to be adequate for detecting neutron-induced chemical
      transmutation of vanadium to chromium under standard reactor conditions, when
      used with long path length cells. It was observed that the absorbance does not
      change on electron irradiation, suggesting that radiolytic effects due to beta
      decay, if any, do not interfere in the measurement of neutron-induced changes. In
      addition to its potential for neutron dosimetry, this is the first report of a
      simple and direct method of estimation of Cr in vanadium matrix at sub ppm level.

PMID- 15249027
TI  - Low temperature FTIR spectra and hydrogen bonds in polycrystalline cytidine.
AB  - FTIR spectra of polycrystalline samples of cytidine, pure and containing a small
      quantity of N(O)H or N(O)D groups (<20%), were measured in KBr pellets from 4000
      to 400 cm(-1) at temperatures from 300 to 20K. For the first time the bands of
      the narrow isotopically decoupled proton stretching vibration mode (nu(1)) of OH-
      and NH- groups were found; their number corresponds to the number of H-bonds in
      crystal according to structural data. The FTIR spectra at low temperature in the
      out-of-plane bending nu(4) proton mode range (lower than 1000 cm(-1)) of N(O)H
      groups revealed narrow bands, which correspond to nu(1) bands together with
      several "extra" bands, which are influenced by the isotopic exchange and (or)
      cooling. All of them have their counterparts in the N(O)D-substance spectrum with
      an isotopic frequency ratio of 1.30-1.40. The "extra" bands are assigned to the H
      bound OH and NH protons, which are disordered and cannot be seen with X-ray
      crystal structure analysis. The peak positions of both mode bands (expressed as
      the red shift of nu(1) or blue shift of nu(4) modes relatively free molecules)
      were used for the estimation of the energy of different H-bonds using previously
      established empirical correlations between spectral and thermodynamic parameters
      of hydrogen bonds. The correlation of the red shift and H-bond length is also
      confirmed for all five H-bonds of cytidine.

PMID- 15249028
TI  - Flow injection chemiluninescence for detecting picogram amounts of dobesilate in
      human urine.
AB  - A sensitive method for the determination of dobesilate in pharmaceutical
      preparations and human urine is described by using controlled-reagent-release
      technology. The method entailed the use of luminol and periodate, which are
      immobilized on anion exchange resin and react in alkaline medium, giving
      chemiluminescence (CL) at 425 nm. Dobesilate was detected by measuring the
      decrease of CL intensity, and which was observed linear over the dobesilate
      concentration range of 10-600 pg ml(-1), and the limit of detection was 3.5 pg
      ml(-1) (3sigma) and a relative standard deviation of less than 3.0%. At a flow
      rate of 2.0 ml min(-1), the determination of dobesilate, including sampling and
      washing, could be performed in 0.5 min, giving a throughput of about 120 times
      per hour. The proposed method has an extremely low limit of detection down to 3.5
      pg ml(-1), thus it can be applied directly in the assay of human urine without
      any pre-treatment. It was also found that the dobesilate concentration reached
      its maximum after orally administrated for 3.5h, and the excretion ratio in 24h
      was 58.8% in the body of volunteers.

PMID- 15249029
TI  - The synthesis and structural characterisation of [Ru(eta-Cp)(dppf)SnBr3].
AB  - The reaction of [Ru(eta-Cp)(dppf)N(3)] (1) with equimolar amount of SnBr(2)
      yielded an interesting heterotrimetallic compound [Ru(eta-Cp)(dppf)SnBr(3)] (2)
      (dppf: 1,1'-bis-diphenylphosphinoferrocene). Compounds 1 and 2 were characterised
      by IR, NMR (1H, 13C, 31P and 119Sn), and 2, additionally, by 57Fe and 119Sn
      Mossbauer spectroscopy and X-ray crystallography. The latter results were as
      follows: monoclinic, C2/c, a = 32.8879(4)A, b = 11.9888(2)A, c = 20.8986(3)A,
      beta = 92.545(1)degrees, V = 8231.9(2)A(3), Z =8.

PMID- 15249030
TI  - In situ speciation studies of copper in the electroplating sludge under an
      electric field.
AB  - Speciation of copper in the electrokinetic treatments of an industrial sludge was
      studied by in situ extended X-ray absorption fine structural (EXAFS) and X-ray
      absorption near-edge structural (XANES) spectroscopies in the present work. The
      least-square fits (LSF) of the XANES spectra indicated that the main copper
      species in the sludge were Cu(NO)(3) (82%) and adsorbed copper (Cu/SiO(2)) (17%).
      Copper in the sludge possessed a Cu-O bond distance of 1.97A with a coordination
      number (CN) of 3.8. In the second shells, the bond distance of Cu-(O)-Si was
      3.03A with a CN of 1.5. Most of Cu/SiO(2) was dissolved in the aqueous phase
      since little Cu-(O)-Si species in the sludge was found after 180 min of the
      electrokinetic treatments. About 69% of total Cu(II) was dissolved into the
      aqueous phase and 51% of which was migrated to the cathode under the electric
      field (5V cm(-1)) for 180 min.

PMID- 15249031
TI  - Spectroscopic studies on the photoeffects on some metallocenes in the presence of
      chloroform molecules confined in poly(methyl methacrylate) thin films.
AB  - The changes in the electronic absorption spectra (UV-Vis) (after photoexcitation)
      of poly(methyl methacrylate) (PMMA) thin films doped with a metallocene and
      containing chloroform molecules as impurities, have been studied as a function of
      photoexcitation wavelength (210-750 nm), photoexcitation time (duration), amount
      of metallocene in the film and amount of chloroform molecules present in the
      film. Photoeffects on the metallocenes have been observed, which depend
      significantly on the nature of the central metal atom of the metallocene and the
      results have been discussed on the basis of the electronic configuration of the
      metallocenes, which is under study.

PMID- 15249032
TI  - Raman microscopy of autunite minerals at liquid nitrogen temperature.
AB  - Uranyl micas are based upon (UO(2)PO(4))(-) units in layered structures with
      hydrated counter cations between the interlayers. Uranyl micas also known as the
      autunite minerals are of general formula M(UO2)2(XO4)2 x 8-12H2O where M may be
      Ba, Ca, Cu, Fe(2+), Mg, Mn(2+) or 1/2(HA1) and X is As or P. The structures of
      these minerals have been studied using Raman microscopy at 298 and 77K. Six
      hydroxyl stretching bands are observed of which three are highly polarised. The
      hydroxyl stretching vibrations are related to the strength of hydrogen bonding of
      the water OH units. Bands in the Raman spectrum of autunite at 998, 842 and 820
      cm(-1) are highly polarised. Low intensity band at 915 cm(-1) is attributed to
      the nu(3) antisymmetric stretching vibration of (UO(2))(2+) units. The band at
      820 cm(-1) is attributed to the nu(1) symmetric stretching mode of the
      (UO(2))(2+) units. The (UO(2))(2+) bending modes are found at 295 and 222 m(-1).
      The presence of phosphate and arsenate anions and their isomorphic substitution
      are readily determined by Raman spectroscopy. The collection of Raman spectra at
      77K enables excellent band separation.

PMID- 15249033
TI  - Spectroscopic studies on Mn(II), Co(II), Ni(II), and Cu(II) complexes with N
      donor tetradentate (N4) macrocyclic ligand derived from ethylcinnamate moiety.
AB  - Manganese(II), cobalt(II), nickel(II), and copper(II) complexes are synthesized
      with a novel tetradentate ligand, viz. 1,5,9,13-tetraaza-6,14-dioxo-8,16
      diphenylcyclohexadecane (L) and characterized by the elemental analysis, molar
      conductance measurements, magnetic susceptibility measurements, mass, 1H NMR, IR,
      electronic, and EPR spectral studies. The molar conductance measurements of the
      complexes in DMSO correspond to be nonelectrolyte nature for Mn(II), Co(II), and
      Cu(II) whereas 1:2 electrolytes for Ni(II) complexes. Thus, these complexes may
      be formulated as [M(L)X(2)] and [Ni(L)]X(2), respectively (where M = Mn(II),
      Co(II), and Cu(II) and X = Cl- and NO(3-)). On the basis of IR, electronic, and
      EPR spectral studies an octahedral geometry has been assigned for Mn(II) and
      Co(II) complexes, square-planar for Ni(II) whereas tetragonal for Cu(II)
      complexes. The ligand and its complexes were also evaluated against the growth of
      bacteria and pathogenic fungi in vitro.

PMID- 15249034
TI  - Hydrogen bonding in selected vanadates: a Raman and infrared spectroscopy study.
AB  - Water plays an important role in the stability of minerals containing the deca
      and hexavanadates ions. A selection of minerals including pascoite, huemulite,
      barnesite, hewettite, metahewettite, hummerite has been analysed. Infrared
      spectroscopy combined with Raman spectroscopy has enabled the spectra of the
      water HOH stretching bands to be determined. The use of the Libowitsky type
      function allows for the estimation of hydrogen bond distances to be determined.
      The strength of the hydrogen bonds can be assessed by these hydrogen bond
      distances. An arbitrary value of 2.74A was used to separate the hydrogen bonds
      into two categories such that bond distances less than this value are considered
      as strong hydrogen bonds whereas hydrogen bond distances greater than this value
      are considered relatively weaker. Importantly infrared spectroscopy enables the
      estimation of hydrogen bond distances using an empirical function.

PMID- 15249035
TI  - Synthesis of a novel host molecule of cross-linking-polymeric-beta-cyclodextrin-o
      vanillin furfuralhydrazone and spectrofluorimetric analysis of its identifying
      cadmium.
AB  - A novel host inclusion complex of cross-linking-polymeric-beta-cyclodextrin-o
      vanillin furfuralhydrazone (beta-CDP-OVFH) was synthesized and characterized with
      IR and 1H NMR spectra to confirm its structure. The coordination reaction of the
      host reagent with Cd(2+) was studied and the optimum reacting conditions were
      observed carefully. A highly selective and sensitive spectrofluorimetric
      determination of trace amount of cadmium was proposed based on the reaction of
      Cd(2+) with beta-CDP-OVFH in ammonia water-ammonium acetate buffer medium of pH =
      11.0. The molar ratio of beta-CDP-OVFH to Cd(2+) was 1:1. The maximum excitation
      and emission wavelengths were 393 and 494 nm, respectively. The linear range of
      this method was from 3.0 to 500 microg l(-1) with a detection limit of 0.80
      microg l(-1). The effect of interferences in the determination of cadmium was
      investigated and the results showed that the host reagent had quite high capacity
      of identifying Cd(2+). The proposed method was successfully applied to the
      determination of trace amount of Cd(2+) in mussel and tea samples.

PMID- 15249036
TI  - Characterization of lecithin:cholesterol acyltransferase expressed in a human
      lung cell line.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme for the transfer of
      mammalian cholesterol from peripheral tissues to the liver. In patients deficient
      in LCAT, serum cholesterol levels rise and can lead to corneal opacity,
      proteinuria, anemia, and kidney failure. As early as 1968, relatively low volume
      transfusion of normal plasma was shown to temporarily correct the abnormal
      lipoprotein profiles in LCAT-deficient patients. However, despite the cloning,
      study, and extensive expression of LCAT in mammalian cell lines, there is still
      no viable, clinical therapy for LCAT deficiency. The current study was initiated
      to provide a source of recombinant human LCAT for enzyme replacement therapy.
      Accordingly, human LCAT has been cloned and expressed for the first time in a
      human cell line. The recombinant LCAT secreted by these cells was purified by
      phenyl-Sepharose chromatography, analyzed to determine the nature of its
      glycosylation, and tested for its enzymatic properties. The activity and basic
      kinetic parameters for the enzyme were determined using both a fluorescent water
      soluble substrate and a macromolecular (proteoliposome) substrate. The enzymatic
      properties and the carbohydrate components of the recombinant LCAT were all
      sufficiently similar to those of the circulating human plasma enzyme, suggesting
      that this source of LCAT may be appropriate for use in some form of enzyme
      replacement therapy.

PMID- 15249037
TI  - Secretion, purification, and characterization of a recombinant Aspergillus oryzae
      tannase in Pichia pastoris.
AB  - Tannase (tannin acyl hydrolase) is an industrially important enzyme produced by a
      large number of fungi, which hydrolyzes the ester and depside bonds of
      gallotannins and gallic acid esters. In the present work, a tannase from
      Aspergillus oryzae has been cloned and expressed in Pichia pastoris. The
      catalytic activity of the recombinant enzyme was assayed. A secretory form of
      enzyme was made with the aid of Saccharomyces cerevisiae alpha-factor, and a
      simple procedure purification protocol yielded tannase in pure form. The
      productivity of secreted tannase achieved 7000 IU/L by fed-batch culture.
      Recombinant tannase had a molecular mass of 90 kDa, which consisted of two kinds
      of subunits linked by a disulfide bond(s). Our study is the first report on the
      heterologous expression of tannase suggesting that the P. pastoris system
      represents an attractive means of generating large quantities of tannase for both
      research and industrial purpose.

PMID- 15249038
TI  - Expression, purification, and characterization of a novel methyl parathion
      hydrolase.
AB  - The mpd gene coding for a novel methyl parathion hydrolase (MPH) was previously
      reported and its putative open reading frame was also identified. To further
      confirm its coding region, the intact region encoding MPH was obtained by PCR and
      expressed in Escherichia coli as a hexa-His C-terminal fusion protein. The fusion
      protein was purified to homogeneity by metal-affinity chromatography. The enzyme
      activity and zymogram assay showed that the fusion protein was functional in
      degrading methyl parathion. The amino terminal sequencing of the purified
      recombinant MPH indicated that a signal peptide of the first 35 amino acids was
      cleaved from its precursor to form active MPH. A rat polyclonal antiserum was
      raised against the purified mature fusion protein. The results of Western blot
      and zymogram demonstrated that mature MPH in native Plesiomonas sp. strain M6 was
      also processed from its precursor by cleavage of a putative signal peptide at the
      amino terminus. The production of active MPH in E. coli was greatly improved
      after the coding region for the signal peptide was deleted. HPLC gel filtration
      of the purified mature recombinant MPH revealed that the MPH was a monomer.

PMID- 15249039
TI  - Transfected insect cells in suspension culture rapidly yield moderate quantities
      of recombinant proteins in protein-free culture medium.
AB  - Methodology to rapidly express milligram quantities of recombinant proteins
      through the Lipofectin-mediated transfection of insect cells in small-scale,
      protein-free suspension culture is presented. The transfection phase in
      suspension culture was first optimized using the green fluorescence protein
      coupled with FACs analysis to examine the effect of variables such as the
      transfection media, duration, and cell density on transfection efficiency and
      expression level. The recombinant protein production phase was optimized using
      secreted alkaline phosphatase (SEAP) as a reporter protein to evaluate the cell
      seeding density and harvest time. Using this method, 5 secreted, 2 intracellular,
      and 1 chimeric protein were expressed at levels ranging from 6 to 50 mg/L.
      Furthermore, the ability to purify over 2 mg of His(6)-tagged SEAP by immobilized
      metal affinity chromatography from 50 mL insect cell culture medium to greater
      than 95% purity was also demonstrated. This method is suitable for scale-up and
      high-throughput applications.

PMID- 15249040
TI  - Antigen-binding properties of monoclonal antibodies reactive with human TATA
      binding protein and use in immunoaffinity chromatography.
AB  - The TATA-binding protein (TBP) plays a central role in the assembly of most
      eukaryotic transcription initiation complexes. We have characterized 3 monoclonal
      antibodies (mAbs) that react in the far amino-terminal (N-terminal) domain of the
      human TBP molecule (residues 1-99). One of these mAbs (designated 1TBP22) is a
      polyol-responsive monoclonal antibody (PR-mAb) and was adapted to an
      immunoaffinity chromatography procedure for purifying bacterially expressed,
      recombinant human TBP. The epitope for mAb 1TBP22 maps to residues 55-99, which
      includes the polyglutamine region. However, mAb 1TBP22 does not react with poly-l
      glutamine. Human TBP, contained on the pET11a plasmid, was expressed in
      Escherichia coli Rosetta (DE3)pLysS. The cell lysate from 330 ml of induced
      culture was treated with polyethyleneimine (PEI) at 0.5 M NaCl to precipitate the
      nucleic acids. After centrifugation, the supernatant fluid was applied to an
      immunoadsorbent containing mAb 1TBP22. After extensive washing, the TBP was
      eluted with buffer containing 0.75 M ammonium sulfate and 40% propylene glycol.
      Human TPB purified by the immunoaffinity chromatography method was found to be
      active in gel-shift assays and transcription assays. Preliminary data indicate
      that this mAb might be useful for purifying protein complexes containing TBP from
      HeLa cell extracts.

PMID- 15249041
TI  - Expressing and purifying an anti-atherosclerosis polypeptide vaccine in
      Escherichia coli.
AB  - A chimeric polypeptide of TTP-CETPC was successfully expressed as inclusion
      bodies in Escherichia coli by fusing it with the C-terminus of asparaginase and a
      basic amino acid-rich peptide (KR). After partially purified by washing with 0.5%
      (v/v) Triton X-100 in 10 mM PB, the pellet was solubilized in 8 M urea. The
      solution was precipitated with single volume and double volumes of cold ethanol
      for removing impurities. The fusion protein in solution was precipitated with
      triple volumes of ethanol to increase purity and then hydrolyzed with 50 mM
      hydrochloric acid at 55 degrees C for 72 h. The TTP-CETPC polypeptide was
      released after the unique acid-labile aspartylprolyl bond in the fusion protein
      was cleaved by acid. After impurities were removed by adjusting the hydrolysis
      solution pH to 9.45 and then to 8.37, the TTP-CETPC polypeptide was further
      purified by DEAE-cellulose column. The TTP-CETPC containing fractions were eluted
      at 60-80 mM NaCl. The purified TTP-CETPC cysteines were oxidized to form into
      intermolecular disulfide bonded dimers for immunizing mice. Specific anti-CETP
      antibodies in mice serum were assayed by ELISA and Western blot to verify that
      antibodies against CETP had been successfully induced and lasted for more than
      seventeen weeks in vivo.

PMID- 15249042
TI  - Protein aggregation during overexpression limited by peptide extensions with
      large net negative charge.
AB  - Folding of the human coxsackie and adenovirus receptor immunoglobulin (Ig)
      variable-type domain (CAR D1) during overexpression in the Escherichia coli
      cytoplasm was shown previously to be partially rescued by fusion to a 22-residue
      C-terminal peptide. Here, peptide sequence features required for solubilization
      and folding of CAR D1 and similar Ig variable-type domains from two other human
      membrane proteins were investigated. Peptide extensions with net negative charge
      > -6 fully solubilized CAR D1, and approximately half of the peptide-solubilized
      protein was correctly folded. The Ig variable-type domains from human A33 antigen
      and myelin P-zero proteins were only partially solubilized by peptide extensions
      with net charge of -12, however, and only the solubilized P-zero domain appeared
      to fold correctly whereas the A33 domain formed soluble microaggregates of
      misfolded protein. Our results suggest a model where the large net charge of
      peptide extensions increases electrostatic repulsion between nascent
      polypeptides. The resulting decrease in aggregation rate can enable some
      polypeptides to fold spontaneously into their native protein conformations.
      Analysis of the solubility and folding status of sets of structurally homologous
      proteins, such as the Ig variable-type domains described here, during
      overexpression could provide insights into how amino acid and gene sequences
      influence the efficiency of spontaneous protein folding.

PMID- 15249043
TI  - Bacterial cell-free system for high-throughput protein expression and a
      comparative analysis of Escherichia coli cell-free and whole cell expression
      systems.
AB  - Sixty-three proteins of Pseudomonas aeruginosa in the size range of 18-159 kDa
      were tested for expression in a bacterial cell-free system. Fifty-one of the 63
      proteins could be expressed and partially purified under denaturing conditions.
      Most of the expressed proteins showed yields greater than 500 ng after a single
      affinity purification step from 50 microl in vitro protein synthesis reactions.
      The in vitro protein expression plus purification in a 96-well format and
      analysis of the proteins by SDS-PAGE were performed by one person in 4 h. A
      comparison of in vitro and in vivo expression suggests that despite lower yields
      and less pure protein preparations, bacterial in vitro protein expression coupled
      with single-step affinity purification offers a rapid, efficient alternative for
      the high-throughput screening of clones for protein expression and solubility.

PMID- 15249044
TI  - Expression, purification, and human antibody response to a 67 kDa vaccine
      candidate for schistosomiasis japonica.
AB  - Schistosomiasis remains a leading cause of morbidity and mortality in the
      developing tropical world, and vaccines to prevent these infections remain a
      scientific and public health priority. Sj67 is a 67 kDa Schistosoma japonicum
      surface membrane protein homologous to a family of actin-binding proteins. Sj67
      is recognized by a mouse monoclonal antibody (mAb 6) that confers resistance to
      challenge infection in passive transfer experiments. These data support Sj67 as a
      potential vaccine candidate for schistosomiasis japonica. In the present study,
      we report the ligation-independent cloning of a cDNA encoding thioredoxin/elastin
      like polypeptide (ELP)/rSj67 into a pET-32 Xa/LIC vector. Soluble recombinant
      fusion protein (Thio-ELP-rSj67) was expressed and purified using anion-exchange
      and size exclusion chromatography. rSj67 was cleaved from the Thio-ELP fusion
      partner by digestion with Factor Xa protease and purified using hydroxyapatite
      column chromatography. Endotoxin was reduced by absorption to a polymyxin
      support. Purified rSj67 had a molecular weight of 67 kDa and N-terminal
      sequencing confirmed that the first five amino acids of the recombinant protein
      matched the predicted sequence for the Sj67 gene. In Western blot analysis, rSj67
      was recognized by the Sj67 specific mAb 6 antibody. IgG antibodies in sera from
      schistosomiasis infected volunteers living in an endemic area of the Philippines
      (n = 13) recognized rSj67 with 4.7-fold greater median fluorescence compared to
      uninfected North American controls (n = 5) (p < 0.009). Together, these data
      confirm the expression and purification of recombinant Sj67 and its immuno
      reactivity with sera from S. japonicum infected humans.

PMID- 15249046
TI  - Elution of antibodies from a Protein-A column by aqueous arginine solutions.
AB  - Acidic pH is commonly used to elute antibodies from Protein-A affinity column,
      although low pH may result in aggregation of the proteins. As an alternative,
      here arginine was tested as an eluent and compared with a more conventional
      eluent of citrate. Using purified monoclonal antibodies, recovery of antibodies
      with 0.1M citrate, pH 3.8, was less than 50% and decreased further as the pH was
      increased to 4.3. At the same pH, the recovery of antibodies was greatly
      increased with 0.5M arginine and more so with 2M arginine. Even at pH 5.0, 2M
      arginine resulted in 31% recovery, although the elution under such condition
      showed extensive tailing. Such tailing was observed at pH 3.8 when 0.1M citrate
      was used. Size exclusion analysis indicated that the eluted antibodies were
      mostly monomeric whether eluted with citrate or arginine. This demonstrates the
      usefulness of arginine as an efficient eluent for Protein-A chromatography.

PMID- 15249045
TI  - Purification and characterization of Mycobacterium tuberculosis KatG,
      KatG(S315T), and Mycobacterium bovis KatG(R463L).
AB  - Isoniazid, a first-line antibiotic used for the treatment of tuberculosis, is a
      prodrug that requires activation by the Mycobacterium tuberculosis enzyme KatG.
      The KatG(S315T) mutation causes isoniazid resistance while the KatG(R463L)
      variation is thought to be a polymorphism. Much of the work to date focused on
      isoniazid activation by KatG has utilized recombinant enzyme overexpressed in
      Escherichia coli. In this work, native KatG and KatG(S315T) were purified from M.
      tuberculosis, and KatG(R463L) was purified from Mycobacterium bovis. The native
      molecular weight, enzymatic activity, optical, resonance Raman, and EPR spectra,
      K(D) for isoniazid binding, and isoniazid oxidation rates were measured and
      compared for each native enzyme. Further, the properties of the native enzymes
      were compared and contrasted with those reported for recombinant KatG,
      KatG(S315T), and KatG(R463L) in order to assess the ability of the recombinant
      enzymes to act as good models for the native enzymes.

PMID- 15249047
TI  - Expression and characterization of Rv2430c, a novel immunodominant antigen of
      Mycobacterium tuberculosis.
AB  - About 10% of the coding sequence of Mycobacterium tuberculosis corresponds to
      hitherto unknown members of the PE and PPE protein families which display
      significant sequence and length variation at their C-terminal region. It has been
      suggested that this could possibly represent a rich source of antigenic variation
      within the pathogen. We describe the purification and biophysical
      characterization of the recombinant PPE protein coded by hypothetical ORF
      Rv2430c, a member of the PPE gene family that was earlier shown to induce a
      strong B cell response. Expression of the recombinant PPE protein in Escherichia
      coli led to its localization in inclusion bodies and subsequent refolding using
      dialysis after its extraction from the same resulted in extensive precipitation.
      Therefore, an on-column refolding strategy was used, after which the protein was
      found to be in the soluble form. CD spectrum of the recombinant protein displayed
      predominantly alpha helical content (81%) which matched significantly with in
      silico and web-based secondary structure predictions. Furthermore, fluorescence
      emission spectra revealed that aromatic amino acids are buried inside the
      protein, which are exposed to aqueous environment under 8M urea. These results,
      for the first time, provide evidence on the structural features of PPE family
      protein which, viewed with its reported immunodominant characteristics, have
      implications for other proteins of the PE/PPE family.

PMID- 15249048
TI  - Determination of the complete cDNA sequence, construction of expression systems,
      and elucidation of fibrinolytic activity for Tapes japonica lysozyme.
AB  - The lysozyme of the marine bivalve, Tapes japonica (13.8 kDa), belongs to the
      invertebrate lysozyme family and displays both chitinase and isopeptidase
      activities. We determined the complete cDNA sequence and constructed effective
      expression systems for this enzyme using Escherichia coli (BL21) and Pichia
      pastoris. The native and recombinant proteins indicated lysozyme activity and
      isopeptidase activity, including the proteolysis of d-dimer, a plasminolytic
      product of stabilized polymeric fibrin. These results will be utilized for the
      structural and functional study of invertebrate lysozymes, and for the
      development of applications for thrombosis therapies.

PMID- 15249049
TI  - The excised heat-shock domain of alphaB crystallin is a folded, proteolytically
      susceptible trimer with significant surface hydrophobicity and a tendency to self
      aggregate upon heating.
AB  - The lens protein, alpha-crystallin, is a molecular chaperone that prevents the
      thermal aggregation of other proteins. The C-terminal domain of this protein
      (homologous to domains present in small heat-shock proteins) is implicated in
      chaperone function, although the domain itself has been reported to show no
      chaperone activity. Here, we show that the domain can be excised out of the
      intact alphaB polypeptide and recovered directly in pure form through the
      transfer of CNBr digests of whole lens homogenates into urea-containing buffer,
      followed by dialysis-based refolding of digests under acidic conditions and a
      single gel-filtration purification step. The folded (beta sheet) domain thus
      obtained is found to be (a) predominantly trimeric, and to display (b)
      significant surface hydrophobicity, (c) a marked tendency to undergo degradation,
      and (d) a tendency to aggregate upon heating, and on exposure to UV light. Thus,
      the twin 'chaperone' features of multimericity and surface hydrophobicity are
      clearly seen to be insufficient for this domain to function as a chaperone. Since
      alpha-crystallin interacts with its substrates through hydrophobic interactions,
      the hydrophobicity of the excised domain indicates that separation of domains may
      regulate function; at the same time, the fact is also highlighted that surface
      hydrophobicity is a liability in a chaperone since heating strengthens
      hydrophobic interactions and can potentially promote self-aggregation. Thus, it
      would appear that the role of the N-terminal domain in alpha-crystallin is to
      facilitate the creation of a porous, hollow structural framework of >/=24
      subunits in which solubility is effected through increase in the ratio of exposed
      surface area to buried volume. Trimers of interacting C-terminal domains anchored
      to this superstructure, and positioned within its interior, might allow
      hydrophobic surfaces to remain accessible to substrates without compromising
      solubility.

PMID- 15249050
TI  - Over-expression, purification, and characterization of metallo-beta-lactamase
      ImiS from Aeromonas veronii bv. sobria.
AB  - The gene from Aeromonas veronii bv. sobria encoding the metallo-beta-lactamase
      ImiS was subcloned into pET-26b, and ImiS was over-expressed in BL21(DE3)
      Escherichia coli and purified using SP-Sepharose chromatography. This protocol
      yielded over 5 mg of ImiS per liter of growth culture under optimum conditions.
      The biochemical properties of recombinant ImiS were compared with those of native
      ImiS. Recombinant and native ImiS have the same N-terminus of A-G-M-S-L, and CD
      spectroscopy was used to show that the enzymes have similar secondary structures.
      Gel filtration chromatography revealed that both enzymes exist as monomers in
      solution. MALDI-TOF mass spectra showed that the enzymes have a molecular mass of
      25,247 Da, and metal analyses demonstrated that both as-isolated enzymes bind ca.
      0.7 mol of Zn(II). Metal titrations demonstrate that the maximum activity of
      recombinant ImiS occurs when the enzyme binds one equivalent of zinc. Steady
      state kinetic studies reveal that recombinant ImiS is a carbapenemase like native
      ImiS and that the recombinant enzyme exhibits similar kcat and K(m) values for
      the substrates tested, as compared to the native enzyme. This over-expression
      protocol now allows for detailed spectroscopic and mechanistic studies on ImiS as
      well as site-directed mutants of ImiS to be prepared for future
      structure/function studies.

PMID- 15249051
TI  - Structural and functional impairment of an Old Yellow Enzyme homologue upon
      affinity tag incorporation.
AB  - Recently, it has been reported that the previously uncharacterized YqjM protein
      from Bacillus subtilis is a true homologue of the physiologically enigmatic yeast
      Old Yellow Enzyme (OYE). In this study, it was also demonstrated that YqjM is
      involved in the oxidative stress response of B. subtilis, thus highlighting a
      novel direction to pursue the role of the OYE family of proteins in the cell. As
      part of an attempt to pin down the exact physiological role of these enzymes,
      both a N-terminal glutathione S-transferase and a C-terminal histidine-tagged
      form of the protein were created to enable "pull-down" assays and identify
      interacting partners which could aid in the functional definition. However, here
      we report on a comparison of the biochemical properties of the tagged forms with
      the native/untagged YqjM, revealing critical differences in the catalytic
      activities and quaternary structure of the protein forms. UV-visible
      spectrophotometric features as well as steady state and individual half-reaction
      kinetic parameters show that the affinity tagged forms are severely impaired both
      in ligand binding and catalysis. Gel filtration and dynamic light scattering
      studies show that incorporation of a tag also has major effects on the quaternary
      structure of the protein by disrupting the native tetrameric conformation which
      may help to explain the observed differences. The study thus highlights important
      considerations for expression construct design when isolating members of the OYE
      family of proteins.

PMID- 15249052
TI  - Expression, purification, and C-terminal amidation of recombinant human glucagon
      like peptide-1.
AB  - Human glucagon-like peptide-1 (hGLP-1) (7-36) amide, a gastrointestinal hormone
      with a pharmaceutical potential in treating type 2 diabetes mellitus, is composed
      of 30 amino acid residues as a mature protein. We report here the development of
      a method for high-level expression and purification of recombinant hGLP-1 (7-36)
      amide (rhGLP-1) through glutathione S-transferase (GST) fusion expression system.
      The cDNA of hGLP-1-Leu, the 31st-residue leucine-extended precursor peptide, was
      prepared by annealing and ligating of artificially synthetic oligonucleotide
      fragments, inserted into pBluescript SK (+/-) plasmid, and then cloned into pGEX
      4T-3 GST fusion vector. The fusion protein GST-hGLP-1-Leu, expressed in
      Escherichia coli strain BL21 (DE3), was purified by affinity chromatography after
      high-level culture and sonication of bacteria. Following cleavage of GST-hGLP-1
      Leu by cyanogen bromide, the recombinant hGLP-1-Leu was released from fusion
      protein, and purified using QAE Sepharose ion exchange and RP C(18)
      chromatography. After purification, the precursor hGLP-1-Leu was transacylated by
      carboxypeptidase Y, Arg-NH(2) as a nucleophile, to produce rhGLP-1. Electrospray
      ionization mass spectrometry showed the molecular weight was as expected. The
      biological activity of rhGLP-1 in a rat model demonstrated that plasma glucose
      concentrations were significantly lower and insulin concentrations higher after
      intraperitoneal injection of rhGLP-1 together with glucose compared with glucose
      alone (P < 0.001).

PMID- 15249053
TI  - Expression, purification, and kinetic constants for human and Escherichia coli
      pyridoxal kinases.
AB  - Pyridoxal kinase is an ATP dependent enzyme that phosphorylates pyridoxal,
      pyridoxine, and pyridoxamine forming their respective 5'-phosphorylated esters.
      The kinase is a part of the salvage pathway for re-utilizing pyridoxal 5'
      phosphate, which serves as a coenzyme for dozens of enzymes involved in amino
      acid and sugar metabolism. Clones of two pyridoxal kinases from Escherichia coli
      and one from human were inserted into a pET 22b plasmid and expressed in E. coli.
      All three enzymes were purified to near homogeneity and kinetic constants were
      determined for the three vitamin substrates. Previous studies had suggested that
      ZnATP was the preferred trinucleotide substrate, but our studies show that under
      physiological conditions MgATP is the preferred substrate. One of the two E. coli
      kinases has very low activity for pyridoxal, pyridoxine, and pyridoxamine. We
      conclude that in vivo this kinase may have an alternate substrate involved in
      another metabolic pathway and that pyridoxal has only a poor secondary activity
      for this kinase.

PMID- 15249054
TI  - Codon optimization of MTS1 and its expression in Escherichia coli.
AB  - MTS1, which encodes a protein named p16, is an important gene involved in
      tumorigenesis. To increase the expression of p16 in Escherichia coli, MTS1 was
      synthesized de novo by recursive PCR, with codons optimized towards E. coli.
      Studies indicate that N-terminal amino acids of p16 had negative impact on its
      expression in E. coli. The function of p16DeltaN8 is not affected by the absence
      of N-terminal eight amino acids, compared with p16. p16DeltaN8 was expressed in
      E. coli, which reached 22% of total cell proteins. Purified p16DeltaN8 (purity
      was 98%) was delivered into A875 (melanoma), MCF7 (breast cancer), and HeLa
      (cervical cancer) cells by lipofectin. Results show purified p16DeltaN8
      remarkably inhibited the growth of A875 and MCF7 cells, whereas it had little
      effect on HeLa cells.

PMID- 15249055
TI  - SIVmac Gag p27 capsid protein gene expression in potato.
AB  - A cDNA encoding the Simian immunodeficiency virus type (SIV(mac)) Gag capsid
      protein was introduced into Solanum tuberosum cells by Agrobacterium tumefaciens
      mediated transformation methods. The gag gene was detected in the genomic DNA of
      transformed leaf tissues by PCR DNA amplification. Immunoblot analysis of
      transformed potato plant extracts with anti-Gag monoclonal antibody showed that
      biologically active Gag protein was synthesized in transformed tuber tissues.
      Based on ELISA results, recombinant Gag protein made up 0.006-0.014% of total
      soluble tuber protein. The synthesis of SIV Gag in transformed potato tubers
      opens the way for development of Gag-based edible plant vaccines for protection
      against SIV and potentially HIV-1 infection.

PMID- 15249056
TI  - Expression, purification, and characterization of authentic monoferric and apo
      human serum transferrins.
AB  - Transferrin is a bilobal protein with the ability to bind iron in two binding
      sites situated at the bottom of a cleft in each lobe. We have previously
      described the production of recombinant non-glycosylated human serum transferrins
      (hTF-NG), containing a factor Xa cleavage site and a hexa-His tag at the amino
      terminus. Constructs in this background that contain strategic mutations to
      completely prevent iron binding in each lobe or in both lobes have now been
      produced. These monoferric hTFs will allow dissection of the contribution of each
      lobe to transferrin function. In addition, the construct completely lacking in
      the ability to bind iron in either lobe provides an opportunity to assess whether
      hTF has any other functions in addition to iron transport. Following insertion of
      the His-tagged hTF molecules into the pNUT vector, transfection into baby hamster
      kidney cells and selection with methotrexate, the secreted recombinant proteins
      were isolated from the tissue culture medium and characterized with regard to
      their iron binding properties. Significant improvements over our previous
      protocol include: (1) addition of butyric acid at a level of 1mM which leads to a
      substantial increase in protein production (as much as a 65% increase compared to
      control cells); and (2) elimination of an anion exchange column prior to
      isolation on a Qiagen Ni-NTA column which makes purification of the His-tagged
      constructs faster and therefore more efficient. These improvements should be
      applicable to expression of other recombinant proteins in mammalian cells.

PMID- 15249057
TI  - Systematic optimization of active protein expression using GFP as a folding
      reporter.
AB  - Many recombinant proteins have been used as drugs; however, human proteins
      expressed using heterologous hosts are often insoluble. To obtain correctly
      folded active proteins, many optimizations of expression have been attempted but
      usually are found to be applicable only for specific targets. Interleukin-18 (IL
      18) has a key role in many severe disorders including autoimmune diseases, and
      therapeutic approaches using IL-18 have been reported. However, production of IL
      18 in Escherichia coli resulted in extensive inclusion body formation and
      previous conventional screenings of expression conditions could obtain only a
      condition with a low yield. To address the problem, we applied a folding reporter
      system using green fluorescent protein (GFP) for screening of the expression
      conditions for hIL-18. The established system efficiently screened many
      conditions, and optimized conditions for the expression of hIL-18 significantly
      enhanced the final yield of the active protein. Systematic screening using a GFP
      reporter system could be applied for the production of other proteins and in
      other organisms.

PMID- 15249058
TI  - Characteristics, epidemiology and clinical importance of emerging strains of Gram
      negative bacilli producing extended-spectrum beta-lactamases.
AB  - Beta-lactam antimicrobial agents represent the most common treatment for
      bacterial infections and continue to be the leading cause of resistance to beta
      lactam antibiotics among Gram-negative bacteria worldwide. The persistent
      exposure of bacterial strains to a multitude of beta-lactams has induced dynamic
      and continuous production and mutation of beta-lactamases in these bacteria,
      expanding their activity even against the newly developed beta-lactam
      antibiotics. These enzymes are known as extended-spectrum beta-lactamases
      (ESBLs). The majority of ESBLs are derived from the widespread broad-spectrum
      beta-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including
      the CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. In
      recent years, there has been an increased incidence and prevalence of ESBLs.
      ESBLs are mainly found in strains of Escherichia coli and Klebsiella pneumoniae
      but have also been reported in other Enterobacteriaceae strains and Pseudomonas
      aeruginosa. Infections with ESBL-producing bacterial strains are encountered
      singly or in outbreaks, especially in critical care units in hospitals, resulting
      in increasing cost of treatment and prolonged hospital stays. Not only may
      nursing home patients be an important reservoir of ESBL-containing multiple
      antibiotic-resistant organisms, but ambulatory patients with chronic conditions
      may also harbor ESBL-producing organisms.

PMID- 15249059
TI  - Physiology of the thermophilic acetogen Moorella thermoacetica.
AB  - Moorella thermoacetica (originally isolated as Clostridium thermoaceticum) has
      served as the primary acetogenic bacterium for the resolution of the acetyl
      coenzyme A (acetyl-CoA) or Wood-Ljungdahl pathway, a metabolic pathway that (i)
      autotrophically assimilates CO2 and (ii) is centrally important to the turnover
      of carbon in many habitats. The purpose of this article is to highlight the
      diverse physiological features of this model acetogen and to examine some of the
      consequences of its metabolic capabilities.

PMID- 15249060
TI  - Improved methods for producing outer membrane vesicles in Gram-negative bacteria.
AB  - Outer membrane vesicle formation occurs during Gram-negative bacterial growth.
      However, natural production of large amounts of outer membrane vesicles has only
      been described in a few bacterial genera. The purified vesicles of some bacterial
      pathogens have shown potential applications in vaccinology and in antibiotic
      therapy. This study focused on the development of a gene expression system able
      to induce production of large amounts of outer membrane vesicles. The Tol-Pal
      system of Escherichia coli, required to maintain outer membrane integrity, is
      composed of five cell envelope proteins, TolA, TolB, TolQ, TolR and Pal. Tol
      proteins are parasitized by filamentous bacteriophages and by colicins. The phage
      infection process and colicin import require, respectively, the N-terminal domain
      of the minor coat g3p protein and the translocation domain of colicins, with both
      domains interacting with Tol proteins. In this study, we show that the
      periplasmic production of either Tol, g3p or colicin domains was able to
      specifically destabilize the E. coli or Shigella flexneri cell envelope and to
      induce production of high amounts of vesicles. This technique was further found
      to work efficiently in Salmonella enterica serovar Typhimurium.

PMID- 15249061
TI  - Reconstruction and computation of microscale biovolumes using geographical
      information systems: potential difficulties.
AB  - Biofilms are bacterial colonies enveloped in a matrix of extracellular polymeric
      secretions. Confocal scanning laser microscopy has been used in conjunction with
      different image analysis techniques to investigate the structure of biofilms. A
      major goal is to reconstitute the three-dimensional structure of biofilms, and
      compute or estimate the biovolumes. Our previous research focused on the
      utilization of remote sensing techniques and Geographical Information Systems for
      quantitative analyses of confocal images. The present study investigates
      potential problems in microbial imaging, and uses two approaches, the program
      COMSTAT and a Geographical Information Systems-based method, to reconstitute
      three-dimensional structures and estimate biovolumes. Volumes of thirty
      fluorescent polymeric microspheres with a known diameter were estimated and used
      as a ground truth, to statistically compare both methods. In a next step, the two
      approaches were used to estimate the biovolume of a section through a Pseudomonas
      aeruginosa biofilm. Difficulties were encountered in image acquisition due to the
      optical properties of the microbeads. Our results indicate that the Geographical
      Information Systems approach produced results consistent with the existing
      COMSTAT approach, and close to theoretical values, despite many problems inherent
      to each phase of this process. Also, the image classification process encountered
      several limitations. It is suggested that the unique constraints of the
      microscopic world may generate additional problems, especially related to image
      classification.

PMID- 15249062
TI  - A new family of conditional replicating plasmids and their cognate Escherichia
      coli host strains.
AB  - We constructed a family of conditionally replicating plasmids, the pTX1 family,
      which are based on the IncPalpha oriV origin of replication that is dependent on
      the trfA-encoded protein. We constructed several Escherichia coli derivatives
      expressing trfA from different chromosomal loci, which can be transduced by phage
      P1 to any E. coli strain. The pTX1 plasmids also carry the oriTRP4 origin of
      transfer, and can be conjugated to E. coli, Vibrio cholerae and likely to a broad
      range of bacteria from the commonly used donor strains SM10 and S17-1, which
      sustain replication of the plasmids through the trfA gene carried by their
      integrated RP4. If TrfA is not provided in trans, these plasmids behave as
      suicide vectors. As such they can be used as a platform for a variety of
      applications such as those developed on the popular conditionally replicating
      plasmids carrying the oriVR6Kgamma origin of replication that is controlled by
      the Pi protein. Their ability to be used as efficient suicide vectors for gene
      disruption in V. cholerae has been demonstrated.

PMID- 15249063
TI  - An innovative technique for inoculating recombinant baculovirus into the silkworm
      Bombyx mori using lipofectin.
AB  - The insect baculovirus expression system is one of the most effective eukaryotic
      expression systems known, and has been widely used to produce numerous
      recombinant proteins. The current traditional inoculation method consists of
      injecting recombinant baculovirus directly into insects, thus causing potential
      contamination to the environment due to virus diffusion during the inoculation
      process. In the present experiment, we directly introduced baculovirus DNA into
      silkworms using a cationic lipofectin reagent instead of directly injecting the
      virus. This new method produced the same infection results as the traditional
      method. A new safe infection technique without direct use of the virus was thus
      developed.

PMID- 15249064
TI  - Bacterial deposition in porous medium as impacted by solution chemistry.
AB  - Bacterial transport in porous medium was investigated by means of column
      experiments using typical rod-shaped bacteria of Escherichia coli and Pseudomonas
      fluorescens. Mobility of E. coli and P. fluorescens in silica gel decreased with
      increasing ionic strength of the solution. In the presence of nonionic
      surfactants, the mobility of E. coli and P. fluorescens increased, and this was
      more pronounced at lower than at higher ionic strength. Bacterial transport in
      the porous medium was described by the equilibrium-kinetic two-region model and
      bacterial deposition was assumed to occur in the kinetic adsorption region only.
      Quantified bacterial deposition from bacterial column breakthrough curves was
      related to electrostatic and Lifshitz-van der Waals interactions between
      bacterial cells and medium surfaces. It was found that electrostatic interactions
      played a more important role than Lifshitz-van der Waals interactions in
      determining bacterial deposition in the porous medium, and were actually the
      barrier for bacteria to attach to the porous medium.

PMID- 15249065
TI  - Influence of environmental cues on transcriptional regulation of foo and clp
      coding for F165(1) and CS31A adhesins in Escherichia coli.
AB  - F165(1) (foo) and CS31A (clp) are bacterial adhesins synthesized by Escherichia
      coli strains associated with diarrhea and septicemia in piglets and calves. They
      belong to the P-regulatory family and as such are subject to a phase variation
      control mediated by Lrp (leucine responsive regulatory protein) and regulators
      homologous to PapI. Analysis of expression of transcriptional fusions between the
      fooB or fooI promoters and lacZ showed that Lrp is an activator of foo and fooI
      transcription, whereas it represses clp transcription. Furthermore, foo phase
      variation leads to a large majority of phase-ON cells, whereas clp phase
      variation leads to a majority of phase-OFF cells. We compared the influence of
      several environmental cues on foo and clp expression, with special attention to
      the effects of leucine and alanine known to be mediated by Lrp. Inhibition or
      significant repression of foo and clp transcription was observed at low
      temperature, in LB medium, and in the presence of glucose, alanine, or leucine.
      Glucose repression of foo but not of clp was totally relieved by addition of
      cAMP. Osmolarity and pH had little effect. Alanine but not leucine, and LB medium
      inhibited foo and clp phase variation, locking cells in the OFF phase. Low
      temperature inhibited clp phase variation and altered the switch frequency of foo
      phase variation, leading to more phase-OFF cells. Glucose altered the phase
      variation of both operons, increasing the number of phase-OFF cells in the
      population. The regulation pattern of foo and clp is consistent with F165(1) and
      CS31A production in low nutrient environments, even at moderately acidic pH or
      high osmolarity.

PMID- 15249066
TI  - Genomic and phenotypic comparison of Bacillus fumarioli isolates from geothermal
      Antarctic soil and gelatine.
AB  - Bacillus fumarioli was originally isolated from geothermal soils in continental
      and maritime Antarctica, and recently, it has been shown to be a frequent
      contaminant of gelatine extracts obtained from European and American production
      plants. These habitats are geographically widely separated, share similar
      temperature and pH conditions, but have substantially different organic loads.
      Because of the prevalence in gelatine extracts and the dissimilarity of this
      habitat to geothermal soil, a comparative study was performed to assess the
      diversity among B. fumarioli strains and reveal possible intraspecies differences
      that might correspond to their niches of origin. Genomic (rep-PCR, 16S rDNA
      sequencing, DNA-DNA hybridisations) and phenotypic techniques (analysis of fatty
      acid content, total cellular proteins, metabolic and morphological traits)
      illustrate the very close relationship between isolates from the two niches. An
      abundant protein band was demonstrated for gelatine isolates only. This band was
      shown to result from a protein with high similarity to a stress response protein.
      Furthermore, subtractive hybridisation revealed genomic differences between
      Antarctic and gelatine isolates that may indicate adaptive evolution to a
      specific environment.

PMID- 15249067
TI  - GlnB is specifically required for Azospirillum brasilense NifA activity in
      Escherichia coli.
AB  - The Azospirillum brasilense transcription regulator NifA and the nitrogen-status
      signaling proteins GlnB, GlnZ and GlnK were expressed in Escherichia coli and
      analyzed for their ability to activate nif gene expression. When expressed
      separately, none of the proteins were able to activate nifH promoter expression
      in any tested conditions; in contrast, nifH expression was observed in cells
      grown in the absence of ammonium and oxygen and when expressing simultaneously
      NifA and GlnB proteins, but not when expressing NifA and GlnZ or GlnK. Our
      results show that the GlnB protein is required for transcription activation by
      Azospirillum brasilense NifA and it cannot be replaced by GlnZ or GlnK.

PMID- 15249068
TI  - Detection of pigment network in dermatoscopy images using texture analysis.
AB  - Dermatoscopy, also known as dermoscopy or epiluminescence microscopy (ELM), is a
      non-invasive, in vivo technique, which permits visualization of features of
      pigmented melanocytic neoplasms that are not discernable by examination with the
      naked eye. ELM offers a completely new range of visual features. One such
      prominent feature is the pigment network. Two texture-based algorithms are
      developed for the detection of pigment network. These methods are applicable to
      various texture patterns in dermatoscopy images, including patterns that lack
      fine lines such as cobblestone, follicular, or thickened network patterns. Two
      texture algorithms, Laws energy masks and the neighborhood gray-level dependence
      matrix (NGLDM) large number emphasis, were optimized on a set of 155 dermatoscopy
      images and compared. Results suggest superiority of Laws energy masks for pigment
      network detection in dermatoscopy images. For both methods, a texel width of 10
      pixels or approximately 0.22 mm is found for dermatoscopy images.

PMID- 15249069
TI  - Breast volume denoising and noise characterization by 3D wavelet transform.
AB  - Breast imaging through cone-beam computed tomography provides a digital breast
      volume, with which the three-dimensional (3D) breast tissues can be analyzed.
      Data denoising, as a preprocessing step for subsequent volumetric breast
      segmentation is always needed. In this paper, we report a volumetric denoising
      technique by a separable 3D wavelet transform (WT), i.e. a '2D WT plus 1D WT'
      scheme. Specifically, the scheme performs two-dimensional (2D) wavelet denoising
      on a stack of slice images of the breast volume, followed by one-dimensional (1D)
      wavelet denoising along the stacking direction. The denoising is achieved by
      wavelet decomposition, high-pass subband attenuation, and wavelet synthesis. A
      one-level 3D WT produces eight subbands occupying the octants of the 3D wavelet
      space. Multilevel WT also provides a multiresolution representation of breast
      volume, i.e. a sequence of low-pass subbands. In general, most noise and
      irregularity features are imparted into the high-pass subbands, which are removed
      or reduced for denoising purpose. Meanwhile, the information in a subband can be
      characterized in terms of energy, variance, and entropy. Through 3D
      visualization, the spatial structure in a subband can also be visually perceived.
      Experimental demonstration with the breast volume reconstructed from a specimen
      is provided.

PMID- 15249070
TI  - Development of the cubic least squares mapping linear-kernel support vector
      machine classifier for improving the characterization of breast lesions on
      ultrasound.
AB  - An efficient classification algorithm is proposed for characterizing breast
      lesions. The algorithm is based on the cubic least squares mapping and the linear
      kernel support vector machine (SVM(LSM)) classifier. Ultrasound images of 154
      confirmed lesions (59 benign and 52 malignant solid masses, 7 simple cysts, and
      32 complicated cysts) were manually segmented by a physician using a custom
      developed software. Texture and outline features and the SVM(LSM) algorithm were
      used to design a hierarchical tree classification system. Classification accuracy
      was 98.7%, misdiagnosing 1 malignant an 1 benign solid lesions only. This system
      may be used as a second opinion tool to the radiologists.

PMID- 15249071
TI  - Automated detection and volume measurement of plexiform neurofibromas in
      neurofibromatosis 1 using magnetic resonance imaging.
AB  - An automated technique for segmentation and volumetric measurement of plexiform
      neurofibromas (PN) in neurofibromatosis 1 using short T1-inversion recovery
      magnetic resonance images is presented. The algorithm described implements
      heuristics derived from human-based recognition of lesions. This technique
      combines region-based with boundary-based segmentation. Two observers, who
      performed semi-automated volume calculations and manual tracings to estimate
      tumor volume, validated this method on 9 PNs of different size and location. This
      automated method was reproducible (coefficient of variation 0.6-5.6%), yielded
      similar results to manual tumor tracings (R = 0.999) and will likely improve the
      ability to measure PNs in ongoing clinical trials.

PMID- 15249072
TI  - Automated segmentation of necrotic femoral head from 3D MR data.
AB  - Segmentation of diseased organs is an important topic in computer assisted
      medical image analysis. In particular, automatic segmentation of necrotic femoral
      head is of importance for various corresponding clinical tasks including
      visualization, quantitative assessment, early diagnosis and adequate management
      of patients suffering from avascular necrosis of the femoral head (ANFH). Early
      diagnosis and treatment of ANFH is crucial since the disease occurs in relatively
      young individuals with an average age of 20-50, and since treatment options for
      more advanced disease are frequently unsuccessful. The present paper describes
      several new techniques and software for automatic segmentation of necrotic
      femoral head based on clinically obtained multi-slice T1-weighted MR data. In
      vivo MR data sets of 50 actual patients are used in the study. An automatic
      method built up to manage the segmentation task according to image intensity of
      bone tissues, shape of the femoral head, and other characters. The processing
      scheme consisted of the following five steps. (1) Rough segmentation of non
      necrotic lesions of the femur by applying a 3D gray morphological operation and a
      3D region growing technique. (2) Fitting a 3D ellipse to the femoral head by a
      new approach utilizing the constraint of the shape of the femur, and employing a
      principle component analysis and a simulated annealing technique. (3) Estimating
      the femoral neck location, and also femoral head axis by integrating anatomical
      information of the femur and boundary of estimated 3D ellipse. (4) Removal of non
      bony tissues around the femoral neck and femoral head ligament by utilizing the
      estimated femoral neck axis. (5) Classification of necrotic lesions inside the
      estimated femoral head by a k-means technique. The above method was implemented
      in a Microsoft Windows software package. The feasibility of this method was
      tested on the data sets of 50 clinical cases (3000 MR images).

PMID- 15249073
TI  - Simplification of analysis procedures in inter-subject studies with cardiac PET
      imaging.
AB  - Quantitative analysis in positron emission tomography imaging usually
      necessitates several studies carried out under the same protocol in order to get
      functional or metabolic parameter values with low variations. Apart from subject
      preparation and measurements in similar conditions, the data analysis should be
      done as uniformly as possible. In this work we report PET data obtained in normal
      and ischemic rats, measured with (13)N-ammonia and (11)C-acetate to extract
      myocardial blood flow and oxygen consumption, and analysed with the usual region
      of interest (ROI) drawing method in each rat individually, in comparison to a new
      method based on resampling all the rat heart images to a common model, then the
      ROIs are drawn once and copied onto each rat image sequence.

PMID- 15249074
TI  - Liver echogenicity: measurement or visual grading?
AB  - OBJECTIVE: Two methods to assess liver echogenicity were compared. METHODS:
      Liver/kidney echogenicity ratio was measured in 41 persons with the ultrasound
      software and visually graded by two radiologists and a radiographer. These
      echogenicity ratios and grades were related to risk factors for fatty liver and
      to liver enzyme levels. RESULTS: These determinants explained 55% of the
      radiologists' mean grades, 14% of the radiographer's and 31% of the measured
      echogenicity ratios. CONCLUSION: Radiologists' visual gradings correlated best
      with the indirect determinants of early liver pathology. Computerized
      measurements may be inferior to visual grading due to the lack of holistic tissue
      diagnostics.

PMID- 15249075
TI  - Galen and tendon surgery.

PMID- 15249076
TI  - Clinical implications of growth factors in flexor tendon wound healing.
AB  - Recent research has focused on the role of growth factors in flexor tendon wound
      healing. These basic science reports have described the identification and
      quantification of various growth factors in in vitro and in vivo models. Although
      these reports have begun to piece together the cascade of events involved in
      flexor tendon wound healing, the clinical relevance for the practicing hand
      surgeon is unclear. Growth factors are cell-secreted proteins that regulate
      cellular functions. These growth factors are involved in cell differentiation and
      growth, including the normal processes of development and tissue repair. Several
      growth factors recently have been identified as playing roles in tendon healing
      including vascular endothelial growth factor (VEGF), insulin-like growth factor
      (IGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor
      (bFGF), and transforming growth factor beta (TGF-beta). In addition, the
      transcription factor NF-kappaB has been implicated in the signaling pathways of
      these growth factors. The purpose of this article is to describe what is known
      about the molecular basis of flexor tendon wound healing, to review the most
      commonly studied growth factors, and to summarize likely clinical applications of
      these growth factors to flexor tendon repair.

PMID- 15249077
TI  - Expression of genes for collagen production and NF-kappaB gene activation of in
      vivo healing flexor tendons.
AB  - PURPOSE: Collagen production and reorientation are core events in the healing of
      tendons and are essential for gaining tensile strength. Intrasynovial flexor
      tendons are composed chiefly of type I collagen; however, type III collagen is
      the earliest to be laid down in the wounds. We investigated the expression of
      genes for type I collagen, type III collagen and its promoter, and nuclear
      transcription factor kappa B (NF-kappaB) in an in vivo tendon injury model in
      chickens. METHODS: Flexor digitorum profundus tendons of the long toes of 12
      white leghorn chickens were transected partially and repaired with the modified
      Kessler method. The repaired tendon segments were harvested at 2, 4, and 8 weeks
      after surgery with 4 chickens used each time. The uninjured tendons from 4 other
      chickens were used as the controls. We determined the expression of the collagen
      and NF-kappaB genes in the tendons with reverse transcription and polymerase
      chain reaction and semiquantitative analysis of gene bands in gel
      electrophoresis. RESULTS: Expression of the type III collagen gene was enhanced
      significantly in the tendons at 2, 4, and 8 weeks after repair. Levels of
      expression of the type III collagen promoter gene were increased significantly in
      the healing tendons at 2 and 4 weeks. Increases in the expression of the type I
      collagen gene occurred later than those of the type III collagen and NF-kappaB
      genes and were significant in the tendons after 4 and 8 weeks. The NF-kappaB gene
      was activated in the tendons at all the healing periods. CONCLUSIONS: Expression
      of type III collagen and its promoter genes is enhanced remarkably during in vivo
      flexor tendon healing. The NF-kappaB gene is activated during the healing
      process. Expression of the type I collagen gene increases remarkably at later
      periods of in vivo tendon healing and is proportional to that of the NF-kappaB
      gene.

PMID- 15249078
TI  - Optimizing biomechanical performance of the 4-strand cruciate flexor tendon
      repair.
AB  - PURPOSE: The purpose of this study was to determine whether increasing the size
      of the locking loop increased the repair strength of the cruciate 4-strand suture
      technique and to quantify the biomechanical properties that various peripheral
      suture techniques provide in the cruciate 4-strand suture technique. METHODS:
      Fifty-six deep flexor tendons harvested from adult sheep hind limbs were divided
      randomly into 7 groups of 8. Four groups were repaired using the cruciate core
      technique without a peripheral suture. The locking loops were set using 10%, 25%,
      33%, or 50% of the tendon width and loaded to failure using a distraction rate of
      20 mm/min. The 3 groups of tendons then were repaired by using the established
      optimal locking loop size. These 3 groups were combined with a simple running,
      cross-stitch, or the interlocking horizontal mattress (IHM) peripheral suture.
      Repairs were tested to failure and the load at a 2-mm gap, load at failure, and
      stiffness were determined for all samples. RESULTS: Repairs with locking loops of
      25% had the greatest biomechanical properties with load to 2-mm gap formation,
      load to failure, and stiffness of 10 N, 46.3 N, and 3.9 N/mm, respectively. Those
      with 33%, 50%, and 10% locking loops followed. Repairs with 10% locking loops
      failed owing to the suture cut out of the tendon. All other groups failed because
      of suture breakage. By using the cruciate core technique with a 25% locking loop
      the IHM/cruciate combination was markedly better than both the cross
      stitch/cruciate and simple running/cruciate combinations. CONCLUSIONS: The ideal
      sized bite of the locking loops for the cruciate repair is 25% of the tendon's
      width. Peripheral sutures are vital to the biomechanical properties of the
      repair. The IHM peripheral suture technique provided the greatest improvement in
      biomechanical properties.

PMID- 15249079
TI  - Reliability of tendon excursion measurements in patients using a color Doppler
      imaging system.
AB  - PURPOSE: The purpose of this study was to assess the test-retest reliability of
      tendon excursion measurements with color Doppler imaging in patients with flexor
      tendon injuries following a modified Kleinert protocol. METHODS: One observer
      performed repeated measurements at 3 different time periods in 13 patients with
      flexor tendon injuries, following a modified Kleinert protocol. The intraclass
      correlation coefficient (ICC), the standard error of measurement (SEM), and
      related indices of measurement error were calculated. RESULTS: Measurements at 10
      day after surgery had an ICC of.88 and an SEM of 1.1 mm. Measurements at 6 weeks
      after surgery had an ICC of.58 and an SEM of 2.0 mm. The measurements after 3
      months had an ICC of.94 and an SEM of 1.2 mm. CONCLUSION: Measurements at 10 days
      and more than 3 months after surgery were reliable and were as reliable as the
      measurements performed on healthy subjects. At 6 weeks after surgery the
      measurements were less reliable. Color Doppler imaging is a reliable and
      noninvasive method to assess tendon excursion, even in patients with small tendon
      excursion movements.

PMID- 15249080
TI  - Spontaneous rupture of the flexor digitorum profundus and superficialis of the
      index finger and the flexor pollicis longus without labor-associated tendon
      loading.
AB  - Closed ruptures of the flexor tendon have been described in association with
      distinct underlying pathologies. The spontaneous rupture of the flexor tendon
      secondary to axial tendon loading alone is infrequent. The previously reported
      cases with spontaneous rupture were mostly men aged 30 to 60 years. In addition,
      rupture occurred during manual labor with the fingers engaged in forceful or
      resisted flexion. Labor-associated forceful usage, in addition to gender and age,
      has been implicated in the pathogenesis of the stressful rupture of the flexor
      tendon. Here we report a case with spontaneous rupture of the flexor digitorum
      profundus (FDP) and superficialis of the index finger as well as the flexor
      pollicis longus (FPL). Unlike the previously reported cases the present patient
      was an elderly woman engaged in no apparent occupational activities. In the
      present case, however, the patient had a particular predisposing condition. The
      patient used only the right hand during her whole lifetime because of a perinatal
      brachial plexus injury on the contralateral arm. The present case may show that
      the tendons of an elderly patient could yield to the axial loading of normal
      levels of activities of daily living when the usage is as incessant as in the
      present patient.

PMID- 15249081
TI  - Partially retained small finger flexor digitorum profundus function despite
      complete tendon loss in the forearm.
AB  - A case of traumatic laceration of the small finger flexor digitorum profundus
      (FDP) tendon in the distal forearm with retained partial active flexion at the
      small finger distal interphalangeal joint (DIP) joint is described. Tendinous
      interconnections between the ring and small FDP tendons and lumbrical muscles may
      permit partial FDP function at the DIP joint despite a complete deficit of the
      proximal tendon.

PMID- 15249082
TI  - The correction of ulnar claw fingers: a follow-up study comparing the extensor-to
      flexor with the palmaris longus 4-tailed tendon transfer in patients with
      leprosy.
AB  - PURPOSE: The extensor to flexor 4-tailed tendon transfer (EF4T) and the palmaris
      longus 4-tailed tendon transfer (PL4T) are 2 surgical procedures used to correct
      intrinsic paralysis of the hand in leprosy. The EF4T traditionally is the more
      common procedure and requires the transfer of a wrist extensor muscle. The PL4T
      requires the transfer of the palmaris longus and morbidity is expected to be
      lower. A follow-up study was performed to determine whether the clinical outcome
      of the PL4T is superior to the EF4T procedure in leprosy patients with ulnar claw
      fingers that are considered mobile before surgery. METHODS: Fifty-five patients
      presented 65 affected hands, of which 40 hands had the PL4T and 25 had the EF4T
      procedure. Each hand was assessed before surgery and at follow-up evaluation by
      predetermined angle measurements, standardized photographs, mechanical function,
      and patient satisfaction. Each hand was given an overall technical grade
      according to previously published standards. RESULTS: After an average follow-up
      period of 33 months there was no statistically significant difference in the
      technical outcome or patient satisfaction between the 2 tendon transfer
      procedures. CONCLUSIONS: Whenever the palmaris longus is available it may be
      considered to be the motor tendon of choice to undertake a many-tailed procedure
      for claw finger reconstruction in mobile hands paralyzed by leprosy. The palmaris
      longus should be considered as a possible motor tendon when correcting intrinsic
      muscle paralysis of the hand.

PMID- 15249083
TI  - Residual function in peripheral nerve stumps of amputees: implications for neural
      control of artificial limbs.
AB  - PURPOSE: It is not known whether motor and sensory pathways associated with a
      missing or denervated limb remain functionally intact over periods of many months
      or years after amputation or chronic peripheral nerve transection injury. We
      examined the extent to which activity on chronically severed motor nerve fibers
      could be controlled by human amputees and whether distally referred tactile and
      proprioceptive sensations could be induced by stimulation of sensory axons in the
      nerve stumps. METHODS: Amputees undergoing elective stump procedures were invited
      to participate in this study. Longitudinal intrafascicular electrodes were
      threaded percutaneously and implanted in severed nerves of human amputees. The
      electrodes were interfaced to an amplifier and stimulator system controlled by a
      laptop computer. Electrophysiologic tests were conducted for 2 consecutive days
      after recovery from the surgery. RESULTS: It was possible to record volitional
      motor nerve activity uniquely associated with missing limb movements. Electrical
      stimulation through the implanted electrodes elicited discrete, unitary, graded
      sensations of touch, joint movement, and position, referring to the missing limb.
      CONCLUSIONS: These findings indicate that both central and peripheral motor and
      somatosensory pathways retain significant residual connectivity and function for
      many years after limb amputation. This implies that peripheral nerve interfaces
      could be used to provide amputees with prosthetic limbs that have more natural
      feel and control than is possible with current myoelectric and body-powered
      control systems.

PMID- 15249085
TI  - Functional outcomes in young, active duty, military personnel after submuscular
      ulnar nerve transposition.
AB  - PURPOSE: The purpose of this study was to report on the results of submuscular
      ulnar nerve transposition (SMUNT) for treatment of cubital tunnel syndrome in a
      young, active duty, military population. METHODS: Twenty patients (20
      extremities) were evaluated retrospectively a minimum of 12 months after surgery.
      Outcome analyses were performed using the Disability of the Arm, Shoulder, and
      Hand (DASH) questionnaire and the Bishop-Kleinman rating scales, physical
      examination, return-to-work analysis, evaluation of complication rate, and
      overall patient satisfaction. RESULTS: At an average follow-up evaluation of 24
      months (range, 12-38 mo), 19 patients had returned to full military active duty
      work status. The average duration of limited work capacity after surgery was 4.8
      months (range, 3-7 mo). The DASH scores improved from an average of 32.5 points
      before surgery to 6.2 points after surgery. In 19 patients the functional outcome
      evaluated with the Bishop-Kleinman rating system was excellent. There were no
      poor outcomes using this rating score. Statistically significant improvements in
      both key pinch and grip strength were noted. Complications included one permanent
      and 2 transient neuropraxias of the medial antebrachial cutaneous nerve. Overall
      19 of 20 patients were satisfied with the procedure and would have the surgery
      again if required. CONCLUSIONS: Submuscular ulnar nerve transposition for cubital
      tunnel syndrome provides a reliable rate of return to full active duty work in
      military personnel with good patient satisfaction and minimal complications.

PMID- 15249086
TI  - Unusual complication of an opposition tendon transfer at the wrist: ulnar nerve
      compression syndrome.
AB  - Restoration of thumb opposition by tendon transfer may be necessary in cases of
      severe thenar atrophy caused by long-standing carpal tunnel syndrome. Routing the
      extensor indicis proprius transfer subcutaneously around the ulna to reanimate
      thumb opposition is an accepted procedure and is considered safe. Ulnar nerve
      compression leading to palsy is possible, however, as shown in the patient
      presented. Neurolysis failed to improve the palsy. Rerouting of the transfer deep
      to the ulnar nerve was necessary to treat the iatrogenic condition. Possible
      nerve compression should be kept in mind when planning a tendon transfer around
      the ulnar side of the forearm or carpus and when following up with the patient.
      Early intervention is necessary to prevent permanent sequelae.

PMID- 15249087
TI  - Outcome assessment of hand function after radial artery harvesting for coronary
      artery bypass.
AB  - The radial artery has gained widespread acceptance as a conduit for coronary
      artery bypass. Advantages include minimal donor site discomfort, ease of
      handling, excellent early patency rates, and the possibility of freedom from late
      conduit atherosclerosis. Although most series describe minimal morbidity, a
      significant incidence of radial sensory neuropathy and isolated instances of hand
      claudication and ischemia have been reported. We performed an outcome study
      utilizing the Short Form-36, the Upper Limb-Disabilities of Arm, Shoulder and
      Hand, and a modified self-administered hand diagram to compare 288 patients
      undergoing coronary artery bypass utilizing the radial artery with a control
      group of 174 patients undergoing coronary artery bypass without the radial
      artery. The data were analyzed by the t test for continuous variables and the chi
      square test for categorical variables, and subsequently a multivariate regression
      model was constructed. No patients developed hand claudication or ischemia.
      Although there was an incidence of radial sensory neuropathy of 9.9% associated
      with radial artery harvest, it was not significantly higher than the incidence in
      the control group (5.2%, p =.16). Intrinsic patient factors such as obesity, age,
      diabetes, and peripheral vascular disease were the principal determinants of
      overall health and quality of life issues.

PMID- 15249088
TI  - Nitric oxide involvement in reperfusion injury of denervated muscle.
AB  - PURPOSE: To investigate whether inhibition of inducible nitric oxide synthase
      (iNOS) improves microcirculation in denervated and reperfused skeletal muscle.
      METHODS: The cremaster muscles of 52 rats received iNOS inhibitor 1400W (3 mg/kg)
      or phosphate buffered saline (PBS) and underwent either 3 hours of ischemia and
      1.5 hours of reperfusion or a sham operation. During reperfusion the vessel
      diameters were measured by using intravital videomicroscopy and overall muscle
      blood flow was measured with laser Doppler flowmetry. The expression of NOS
      messenger RNA (mRNA) and protein was determined by using real-time reverse
      transcription polymerase chain reaction and Western blot, respectively. RESULTS:
      1400W treatment significantly increased the mean blood flow of the reperfused
      muscle compared with controls, and this was associated with significantly less
      vasospasm in 10 to 20 microm, 21 to 40 microm, and 41 to 70 microm arterioles.
      The expression of iNOS mRNA and protein in controls increased 23-fold and 6-fold
      from normal, respectively, but was reduced to only a 2-fold increase in the 1400W
      treated muscles. The ischemia/reperfusion (I/R)-induced decrease of endothelial
      NOS (eNOS) and neuronal NOS (nNOS) expression in controls was not significantly
      changed after 1400W treatment. CONCLUSIONS: Our data support a nitric oxide
      mediated mechanism in reperfusion injury and show the importance of inhibition of
      iNOS in reducing reperfusion injury in denervated skeletal muscle. Our results
      suggest potential benefits via inhibition of iNOS to improve clinical outcomes
      not only for hand surgeons who work in the microsurgery field, but also for other
      physicians whose work involves ischemia/reperfusion injury.

PMID- 15249089
TI  - A prospective outcomes study of Swanson metacarpophalangeal joint arthroplasty
      for the rheumatoid hand.
AB  - PURPOSE: Destruction and dislocation of the metacarpophalangeal (MCP) joints are
      common occurrences in patients with rheumatoid arthritis (RA). Disruption of the
      support ligaments around the MCP joints and ulnar deviation of the fingers affect
      hand function and hamper the ability to perform activities of daily living. A
      common surgical intervention is the Swanson Metacarpophalangeal Joint
      Arthroplasty (SMPA), which restores alignment of the fingers. METHODS: We
      conducted a prospective study with 16 patients to determine outcomes of this
      procedure. We present our data from the 6-month and 1-year follow-up periods.
      RESULTS: Functional assessment by grip strength, pinch strength, and Jebsen
      Taylor Test did not improve significantly when compared with preoperative values.
      Subjective assessment by the Michigan Hand Outcomes Questionnaire (MHQ), however,
      did improve significantly. Large improvements were seen in the function,
      activities of daily living, aesthetics, and patient satisfaction domains, with
      preoperative to 1-year postoperative score improvements of 26, 42, 57, and 43
      points, respectively, based on a 100-point scale. Ulnar drift significantly
      decreased 1 year after surgery by an average of 24 degrees and MCP joint range of
      motion increased, but this change was not significant. CONCLUSIONS: Our data show
      that patients with RA who underwent SMPA had significant improvements in patient
      reported outcomes at the 1-year interval. Continued follow-up evaluation of this
      cohort will determine whether these improvements are maintained in the long term.

PMID- 15249090
TI  - Palmar fasciitis and arthritis syndrome associated with metastatic ovarian
      carcinoma: a report of four cases.
AB  - Palmar fasciitis and polyarthritis syndrome (PFPAS) is an uncommon paraneoplastic
      syndrome associated with several malignant neoplasms. We identified 4 patients
      with PFPAS and ovarian carcinoma. Palmar fasciitis, at times severe, and
      inflammatory polyarthritis dominated the clinical presentation in all 4 patients.
      In 3 of our 4 patients the presentation of palmar fasciitis and inflammatory
      polyarthritis preceded the diagnosis of ovarian carcinoma. Magnetic resonance
      scanning and biopsy examination of palmar nodules in one patient revealed
      findings of inflammation and fibrosis. A literature review found 10 other cases
      of PFPAS associated with ovarian carcinoma. Improvement in palmar fasciitis and
      inflammatory arthritis often occurs after successful treatment of the ovarian
      carcinoma. Digital contractures, however, can persist. We recommend a gynecologic
      examination in any woman presenting with the sudden onset of unexplained hand
      pain, palmar inflammatory fasciitis, palmar fibromatosis, and digital
      contractures.

PMID- 15249091
TI  - Arthroscopic resection of arthrosis of the proximal hamate: a clinical and
      biomechanical study.
AB  - PURPOSE: The purpose of this study was to present a series of patients with
      arthrosis of the proximal hamate treated by arthroscopic resection. To further
      investigate this condition a biomechanical study also was undertaken to document
      the effect this proximal hamate resection has on carpal loading. METHODS: Between
      1991 and 2001 there were 23 patients who had arthroscopic proximal hamate
      resection for the treatment of proximal hamate arthrosis. Twenty-one patients
      were available for final follow-up evaluation (average, 4.7 y). Patients were
      evaluated by using a modified wrist score that examined pain relief, patient
      satisfaction, range of motion, and grip strength. Six cadaver wrists had
      resection of the proximal hamate. Loads across the carpal and midcarpal joints
      were documented with pressure-sensitive film before and after proximal hamate
      resection. RESULTS: Ninety-five percent of the patients had a type II lunate.
      Twenty-one of 23 wrists had lunotriquetral tears confirmed on arthroscopic
      examination. Follow-up evaluation revealed 14 excellent, 4 good, 1 fair, and 2
      poor results. Biomechanical studies revealed that resection of 2.4 mm of the
      proximal hamate unloads the hamatolunate articulation without changing the load
      at the triquetrohamate joint. CONCLUSIONS: Arthrosis of the proximal pole of the
      hamate seems to be associated closely with tears of the lunotriquetral joint and
      may be part of the spectrum of ulnar-sided wrist degeneration. Arthroscopic
      resection of the proximal pole of the hamate appears to be a useful treatment in
      patients with symptomatic hamate arthrosis, even in those patients with
      lunotriquetral laxity.

PMID- 15249092
TI  - Capitate-based kinematics of the midcarpal joint during wrist radioulnar
      deviation: an in vivo three-dimensional motion analysis.
AB  - PURPOSE: The purpose of this study was to obtain qualitative and quantitative
      information regarding in vivo 3-dimensional (3D) kinematics of the midcarpal
      joint during wrist radioulnar deviation (RUD). METHODS: We studied the in vivo
      kinematics of the midcarpal joint during wrist RUD in the right wrists of 10
      volunteers by using a technology without radioactive exposure. The magnetic
      resonance images were acquired during RUD. The capitate was registered with the
      scaphoid, the lunate, and the triquetrum by using a volume registration
      technique. Animations of the relative motions of the midcarpal joint were created
      and accurate estimates of the relative orientations of the bones and axes of
      rotation (AORs) of each motion were obtained. RESULTS: The scaphoid, lunate, and
      triquetrum motions relative to the capitate during RUD were found to be similar,
      describing a rotational motion around the axis obliquely penetrating the head of
      the capitate in almost a radial extension/ulnoflexion plane of motion of the
      wrist. The AORs of the scaphoid, the lunate, and the triquetrum were located
      closely in space. In the axial plane the AORs of the scaphoid, lunate, and
      triquetrum formed a radially and palmarly opening angle of 43 degrees +/- 7
      degrees, 41 degrees +/- 11 degrees, and 42 degrees +/- 14 degrees with the wrist
      flexion/extension axis, respectively. CONCLUSIONS: This study reports the in vivo
      3D measurements of midcarpal motion relative to the capitate. Isolated midcarpal
      motion during RUD could be approximated to be a rotation in a plane of a
      radiodorsal/ulnopalmar rotation of the wrist, which may coincide with a motion
      plane of one of the most essential human wrist motions, known as the dart
      throwing motion.

PMID- 15249093
TI  - The incidence of wrist interosseous ligament and triangular fibrocartilage
      articular disc disruptions: a cadaveric study.
AB  - PURPOSE: The purpose of this cadaveric wrist study was to determine the incidence
      and size of defects of the scapholunate interosseous ligament (SLIL),
      lunotriquetral interosseous ligament (LTIL), and triangular fibrocartilage (TFC)
      articular disc, and to determine their relationship to wrist arthrosis. METHODS:
      The status of the SLIL, LTIL, and the TFC articular disc was determined in 96
      cadaveric wrists with an average age of 75 years (range, 61-92 y). The location
      and length of the SLIL and LTIL ligament disruptions and the site of ligament
      detachment were noted. Ligament disruptions were classified into 1 of 3 grades
      based on the size of the ligament disruption and the absence (grade 1 and 2
      disruptions) or presence (grade 3 disruption) of wrist arthrosis. The location,
      size, and configuration of the TFC articular disc disruptions also were noted.
      RESULTS: Disruptions of the SLIL were noted in 34 wrists (35%). There were 20
      grade 1, 4 grade 2, and 10 grade 3 ligament disruptions. The average length of
      ligament disruption was 10.9 mm, or 40% of the length of the ligament. Twenty
      four of 34 SLIL disruptions occurred without wrist arthrosis. Disruptions of the
      LTIL were noted in 47 wrists (49%). There were 23 grade 1, 10 grade 2, and 14
      grade 3 ligament disruptions. The average length of ligament disruption was 7.6
      mm, or 52% of the ligament length. Thirty-three of 47 LTIL disruptions occurred
      without wrist arthrosis. Disruptions of the TFC articular disc were noted in 58
      wrists (60%). The most common patterns of disruption were either a linear defect
      at the radial attachment of the articular disc or a centrally located oval
      defect. Thirty-seven of the 58 TFC articular disc disruptions were noted in
      wrists without distal radioulnar joint (DRUJ) arthrosis. CONCLUSIONS: There is a
      high incidence of SLIL, LTIL, and TFC articular disc disruptions in the cadaveric
      model. Large ligament and TFC articular disc disruptions without wrist arthrosis
      are very common.

PMID- 15249094
TI  - Kienbock's disease in an elderly patient treated with proximal row carpectomy.
AB  - Kienbock's disease most often occurs in the dominant hand of young men with a
      history of manual labor. We report an atypical presentation of stage III
      Kienbock's disease in the nondominant hand of a 70-year-old woman. The patient
      was managed successfully by proximal row carpectomy. The risk factors and cause
      of Kienbock's disease in the elderly may differ from those in the typical younger
      population. The detection of Kienbock's disease in the elderly and the use of
      proximal row carpectomy in advanced cases is emphasized.

PMID- 15249095
TI  - Predicted effects of metacarpal shortening on interosseous muscle function.
AB  - PURPOSE: Metacarpal fractures are common in hand surgery. Metacarpal shortening
      ranging from 2 mm to as much as 10 mm has been deemed acceptable in the
      literature. We examined the effect of metacarpal shortening on interosseous
      muscle architecture and predicted force production capacity based on the standard
      muscle length-tension curve (commonly known as the Blix curve). METHODS: The
      dorsal interosseous muscles between the middle and ring finger metacarpals from 9
      adult human cadaver hands were exposed and studied. The ring finger metacarpal
      was translated proximally in 2-mm increments in relation to a stationary middle
      finger metacarpal. Digital images were obtained and analyzed to define the length
      and orientation of individual muscle fibers with each incremental change in
      position. RESULTS: Interosseous muscle fiber length increased and pennation angle
      decreased uniformly with increasing proximal translation of the ring finger
      metacarpal. At 10 mm of shortening the fiber length had increased to 20.8 +/- 1.8
      mm, or to approximately 125% of optimum fiber length, and the pennation angle had
      decreased to 6.7 degrees +/- 2.2 degrees or by approximately 50%. CONCLUSIONS:
      The interosseous muscles have been shown to have a high fiber-to-muscle length
      ratio. This ratio indicates that these muscles function optimally over a short
      range of lengths, leaving them vulnerable to derangement in function owing to
      alteration in the surrounding bony architecture. Based on the standard muscle
      length--tension relationship we had predicted a steady linear decrease in
      interosseous power with proximal translation of the metacarpal. The results
      indicate an initial linear progression with a plateau at approximately 8 mm of
      shortening. At 2 mm of shortening there is an approximately 8% loss of power
      generation, at 10 mm of metacarpal shortening we predict the interosseous muscle
      to be capable of only approximately 55% of its optimum power compared with the
      resting position.

PMID- 15249096
TI  - Loss of alignment after surgical treatment of posterior Monteggia fractures:
      salvage with dorsal contoured plating.
AB  - PURPOSE: To review the results of internal fixation with a dorsal contoured plate
      in patients with malalignment after internal fixation of a posterior Monteggia
      fracture. METHODS: Seventeen patients with malalignment after surgical treatment
      of a posterior Monteggia fracture were treated with realignment of the ulna and
      fixation with a contoured dorsal plate. Fifteen patients had loose fixation and
      12 patients had subluxation or dislocation of the ulnohumeral joint. Sixteen
      patients had fracture of the radial head and 9 patients had fracture of the
      coronoid process. Nine patients had ancillary procedures on the radial head, 4
      had ancillary procedures on the coronoid, 5 had hinged external fixation, and one
      had fascial arthroplasty. Seven patients had another surgery before the final
      evaluation related to a complication in 6 patients and a to subsequent injury in
      1 patient. RESULTS: At the final evaluation at an average of 59 months the
      fracture was healed and the ulnohumeral joint was reduced concentrically in all
      17 patients. The average arc of elbow flexion was 108 degrees and the average arc
      of forearm rotation was 134 degrees. The average American Shoulder and Elbow
      Surgeons Elbow Evaluation Score was 88. According to the system of Broberg and
      Morrey, the final result was rated excellent for 5 patients, good for 9, fair for
      2, and poor for 1. One patient had fascial arthroplasty as part of the index
      procedure and 9 patients had radiographic signs of ulnohumeral arthrosis.
      CONCLUSIONS: Malalignment after surgical treatment of posterior Monteggia
      fractures often is associated with unstable fixation. Dorsal contoured plating of
      the ulna in combination with other procedures can help salvage a malaligned
      posterior Monteggia fracture with satisfactory function restored in the majority
      of patients.

PMID- 15249097
TI  - The 45 degrees pronated oblique view for volar fixed-angle plating of distal
      radius fractures.
AB  - Distinctive to volar fixed-angle plating of the distal radius, the optimal
      position of the distal fixed-angle support is in the subchondral bone immediately
      proximal to the articular surface. Standard intraoperative radiographic imaging
      of the distal radius during placement of a volar fixed-angle plate does not
      provide adequate visualization of the subchondral bone-distal support interface.
      A 45 degrees pronated oblique view is described to address this specific issue of
      whether volar hardware placed at the immediate subchondral bone level has
      effectively avoided the radiocarpal joint. This is a quite important radiographic
      consideration when pursuing the strategy of volar fixed-angle plating of distal
      radius fractures.

PMID- 15249098
TI  - Percutaneous reduction of incipient malunion of phalangeal neck fractures in
      children.
AB  - PURPOSE: In this article we describe our treatment of partially healed malaligned
      fractures of the phalangeal neck in children. METHODS: This was a retrospective
      study of 8 pediatric patients with phalangeal neck fractures who presented late
      for care to Children's Hospital in Boston. All patients were diagnosed clinically
      and radiographically with advanced partial healing of their fracture in a
      malunited position of extension. The 8 patients were followed up until fracture
      healing and restoration of normal motion and function were achieved. RESULTS: A K
      wire was inserted into the fracture site through the dorsal callus and used to
      mobilize the fracture fragment by breaking down the fracture callus and partially
      healed bone. The wire then was used as a lever arm for fracture reduction. A
      separate wire was used to pin the fracture percutaneously. CONCLUSIONS: This
      treatment corrects the loss of flexion that occurs with a malunion in the
      phalangeal subcondylar fossa. It is a minimally invasive procedure that avoids
      the soft-tissue dissection of an open procedure.

PMID- 15249100
TI  - Cleft hands with six metacarpals.
AB  - PURPOSE: The purpose of this study was to identify children with cleft hands
      whose radiographs showed metacarpal polydactyly with 6 metacarpals to support the
      hypothesis that cleft hand develops not as a result of a longitudinal failure of
      formation but through a process of central polydactyly and osseous syndactyly.
      METHODS: We screened the hand radiographs of all children with a transverse or
      longitudinal deficiency of the upper limb and identified 8 children with cleft
      hands containing 6 metacarpals. RESULTS: Six cleft hands had a missing middle
      finger and consisted of a thumb and index finger separated from the ring and
      small fingers by a V-shaped central cleft. Two children had a more severe form of
      cleft hand with absence of both the index and middle fingers but presence of 6
      metacarpals. CONCLUSIONS: These 8 cleft hands containing 6 metacarpals showed
      progression of polydactyly of the middle finger and osseous syndactyly between
      the 2 middle finger metacarpals and the adjacent index and ring finger
      metacarpals. This contradicts a longitudinal failure of formation mechanism and
      supports the alternative hypothesis that cleft hand, polydactyly, and syndactyly
      develop through a similar teratogenic mechanism. The 2 cleft hands that had more
      severe suppression of the index and middle fingers yet had 6 metacarpal
      polydactyly provided confirmatory evidence that both typical cleft hands and the
      more severe manifestations of cleft hand with absence of multiple digits develop
      through a similar failure of induction mechanism.

PMID- 15249099
TI  - Bone lengthening for congenital differences of the hands and digits in children.
AB  - PURPOSE: We investigated the growth of bones after lengthening to evaluate the
      effectiveness and usefulness of bone lengthening in congenital hand deficiencies.
      METHODS: Bone lengthening was performed to treat congenital hand deficiencies
      including hypoplastic thumb, hypoplasia of the small finger, cleft hand,
      metacarpal synostosis, brachymetacarpia, symbrachydactyly, and amniotic band
      syndrome. A total of 15 patients (1-13 years old) underwent lengthening of 23
      bones. The average of distraction was 10 mm. The mean follow-up period was 59
      months. The length of the bones at follow-up evaluation was measured and then
      compared with the length of the bones immediately after lengthening. The bone
      growth after lengthening, the percentage of growth after lengthening, and the
      growth rate were compared among diagnostic groups. RESULTS: In the cases
      involving older patients the bone length changed little and the growth plates of
      these patients closed naturally soon after lengthening. In contrast, in the cases
      in which the patients were younger than 7 years old the lengthened bones grew
      continuously. The amount of bone growth was different for each disease in the
      younger patients. In patients with amniotic band syndrome the lengthened bones
      grew at the same rate as the bones in the hand. Other diagnoses such as
      symbrachydactyly had a different growth pattern in the hand. CONCLUSIONS: We
      conclude that bone lengthening is a reliable method for the correction of
      congenital differences of the hand. The indications for this procedure must be
      determined while considering the relationship between the specific disease and
      subsequent bone growth.

PMID- 15249101
TI  - The quality of reporting and outcome measures in randomized clinical trials
      related to upper-extremity disorders.
AB  - PURPOSE: Randomized clinical trials can provide strong evidence regarding
      effective treatment options. The quality of reporting and the type of outcome
      measures used are important when judging whether results justify change in
      clinical practice. The aim of this study was to assess the quality of reporting
      of randomized clinical trials related to treatment of upper-extremity disorders,
      published in 4 hand surgical and orthopedic journals during an 11-year period,
      and assess the type of outcome measures used in the trials. METHODS: Eligible
      articles were identified by reviewing all abstracts published in the 4 journals
      from 1992 through 2002. The quality of reporting was assessed by a modified Jadad
      scale that consisted of 3 items (randomization, blinding, and
      withdrawals/dropouts). A higher score (0-5) indicated higher quality. The outcome
      measures were classified according to the International Classification of
      Functioning, Disability and Health into the levels of body function and
      structure, activity, and participation. RESULTS: Of 92 articles reporting
      randomized clinical trials, 40 articles described appropriate randomization
      method that implied they were truly randomized studies, 31 articles did not
      describe the randomization method, and 21 articles (23%) described inappropriate
      randomization methods. Double or single blinding was reported in 33 articles.
      Absence or description of withdrawals/dropouts was shown in 77 articles. The
      median quality score calculated for all 92 articles was 2 (range, 0-5) points.
      The median score for the 28 articles published 1992 through 1996 was 1 (range, 0
      5) points and for the 64 articles published from 1997 through 2002 was 3 (range,
      0-5) points. All trials used outcome measures on body function and structure
      level; 41% used measures of activity and/or participation. CONCLUSIONS: There is
      a need to improve the quality of reporting of upper-extremity randomized clinical
      trials and to increase the use of outcome measures covering different aspects of
      disability.

PMID- 15249103
TI  - Factors influencing residents' decisions to pursue a career in hand surgery: a
      national survey.
AB  - PURPOSE: The number of programs offering hand surgery fellowships has remained
      approximately the same over a 6-year period while the number of fellows within
      these programs has decreased by 46%. This study aimed to identify factors that
      persuaded or dissuaded orthopedic and plastic surgery residents in choosing hand
      surgery as a career. METHODS: We conducted a national survey of final-year
      orthopedic (n = 600) and plastic surgery (n = 177) residents. We developed an
      internet questionnaire based on literature review and focus group discussions. A
      Web site link was sent via e-mail to program directors of accredited orthopedic
      and plastic surgery programs for distribution of this anonymous survey to the
      residents. Factor analysis combined items into an "intellectual issues" category
      and a "lifestyle issues" category. Logistic regression was used to evaluate
      factors that predict an outcome of entering a hand surgery fellowship. RESULTS:
      We achieved a 30% response rate. Respondents and nonrespondents were not
      significantly different in terms of gender and race. After controlling for age,
      gender, marital status, and specialty, residents who enjoyed the intellectual
      issues of the hand surgery field were more likely to pursue a hand surgery
      fellowship (odds ratio = 10.1; 95% confidence interval = 3.3-30.8). Although a
      positive attitude toward lifestyle issues of the hand surgery field tended to be
      associated with pursuit of a hand surgery fellowship, the relationship was much
      weaker (odds ratio = 2.5; 95% confidence interval = 0.8-7.3). CONCLUSIONS:
      Lifestyle issues associated with a career in hand surgery such as low
      reimbursement and long hours were not the most important factors to residents
      when considering a career in the field. Residents pursued hand surgery primarily
      because of factors such as interest in and exposure to this field. To prevent a
      potential shortfall of hand surgeons, both orthopedic and plastic surgery
      programs must strengthen residents' exposure to hand surgery education in their
      training.

PMID- 15249104
TI  - Southern California Society for Surgery of the Hand Journal Club Award.

PMID- 15249105
TI  - Diagnosis of compressive neuropathies in patients with fibromyalgia.

PMID- 15249108
TI  - Increased periodic arousal fluctuations during non-REM sleep are associated to
      superior memory.
AB  - Sleep has been implicated in the plastic cerebral changes that underlie learning
      and memory. The scientific investigation of people with exceptional memory has
      been relatively neglected. We report the results of a polysomnographic
      investigation of an individual with superior memory performance. The sleep
      structure, in terms of sleep induction and maintenance, as well as non-REM and
      REM sleep percentages, were normal. The main finding was an increased number of
      periodic arousal fluctuations during non-REM sleep (measured as cyclic
      alternating pattern, CAP) during two consecutive nights (7-8 S.D. units above
      that observed in age-matched controls). Since CAP rate reflects the structural
      organization of non-REM sleep, this observation supports the hypothesis of a link
      between non-REM sleep and declarative memory performance.

PMID- 15249109
TI  - Sex differences in face gender recognition in humans.
AB  - Human faces are ecologically-salient stimuli. Face sex is particularly relevant
      for human interactions and face gender recognition is an extremely efficient
      cognitive process that is acquired early during childhood. To measure the minimum
      information required for correct gender classification, we have used a pixelation
      filter and reduced frontal pictures (28,672 pixels) of male and female faces to
      7168, 1792, 448 and 112 pixels. We then addressed the following questions: Is
      gender recognition of male and female faces equally efficient? Are male and
      female subjects equally efficient at recognising face gender? We found a striking
      difference in categorisation of male and female faces. Categorisation of female
      faces reduced to 1792 pixels is at chance level whereas categorisation of male
      faces is above chance even for 112 pixel images. In addition, the same difference
      in the efficiency of categorisation of male and female faces was detected using a
      Gaussian noise filter. A clear sex difference in the efficiency of face gender
      categorisation was detected as well. Female subject were more efficient in
      recognising female faces. These results indicate that recognition of male and
      female faces are different cognitive processes and that in general females are
      more efficient in this cognitive task.

PMID- 15249110
TI  - Lesions of the dorsal noradrenergic bundle augment the renin response to blood
      loss but do not alter hypothalamic Fos expression.
AB  - The goal of this study was to determine if the dorsal noradrenergic bundle (DNAB)
      plays an essential role in mediating increased plasma renin activity (PRA) and
      hypothalamic activation, as indicated by increased Fos expression, in response to
      a small volume blood loss in unanesthetized animals. Male Sprague-Dawley rats
      were prepared with bilateral 6-hydroxydopamine or sham lesions of the dorsal
      noradrenergic bundle. In both groups of animals, blood pressure decreased by only
      10-15 mmHg following hemorrhage (10 ml/kg over 15 min). Plasma renin activity
      increased similarly in both groups after 5 ml/kg blood loss, but showed a
      significantly greater increase after 10 ml/kg blood loss in animals with 6
      hydroxydopamine lesions than in those with sham lesions (increase of 13.8 +/- 2.0
      ng/ml/h versus 8.4 +/- 1.2 ng/ml/h; P < 0.025). There were numerous Fos
      immunoreactive cell nuclei in the supraoptic nucleus (SON) and parvicellular
      paraventricular hypothalamic nucleus (PVN) of hemorrhaged animals. The number of
      Fos-positive neurons did not differ between groups, indicating that the dorsal
      noradrenergic bundle does not convey the primary drive for supraoptic and
      paraventricular nucleus activation during blood loss. However, one or more of the
      forebrain regions innervated by the dorsal noradrenergic bundle may attenuate the
      sympathetic outflow that initiates renin release in response to hemorrhage.

PMID- 15249111
TI  - Axonal connections from posterior paralaminar thalamic neurons to basomedial
      amygdaloid projection neurons to the lateral entorhinal cortex in rats.
AB  - Stimulation of amygdaloid nuclei and emotionally relevant stimuli are known to
      influence the induction and maintenance of long-term potentiation in the
      hippocampal formation and the formation of long-term declarative memories.
      Because the thalamic projection from the posterior paralaminar thalamic nuclei is
      an important sensory afferent projection to amygdaloid nuclei mediating the fast
      acquisition of fear-potentiated behavior, we were interested in verifying whether
      this projection establishes synaptic contacts on amygdala neurons that project to
      the hippocampal formation. Thalamic afferents were labeled with the anterograde
      tracer Phaseolus vulgaris leucoagglutinin and amygdalo-hippocampal neurons were
      identified by injection of the retrograde tracer Fluorogold into the lateral
      entorhinal cortex. A massive overlap of both projection systems was observed
      especially in the anterior basomedial nucleus of the amygdala. Light microscopic
      examination revealed that single anterogradely labeled boutons were in close
      apposition to retrogradely labeled neurons suggesting synaptic contacts. The
      occurrence of such synaptic contacts was confirmed with electron microscopy.
      However, despite the massive overlap of anterogradely labeled axons and
      retrogradely labeled neurons observed at the light microscopic level, electron
      microscopy revealed that only 10% of all labeled profiles make direct contacts on
      each other; anterogradely labeled boutons predominantly contacted unlabeled
      profiles but synapses with direct contact between labeled profiles were rare.
      Altogether the findings demonstrate that the thalamic connection with the
      basomedial nucleus of the amygdala may represent an anatomical substrate for
      modulating amygdala output to the hippocampal formation.

PMID- 15249112
TI  - Role of the cerebellum in implicit motor skill learning: a PET study.
AB  - To depict neural substrates of implicit motor learning, regional cerebral blood
      flow was measured using positron emission tomography (PET) in 13 volunteers in
      the rest condition and during performance of a unimanual two-ball rotation task.
      Subjects rotated two balls in a single hand; a slow rotation (0.5 Hz) was
      followed by two sessions requiring as rapid rotation as possible. The process was
      repeated four times by a single hand (Block 1) and then by the opposite hand
      (Block 2). One group of volunteers began with the right hand (n = 7), and the
      other with the left (n = 6). Performance was assessed by both quickness and
      efficiency of movements. The former was assessed with the maximum number of
      rotation per unit time, and the latter with the electromyographic activity under
      constant speed of the movement. Both showed learning transfer from the right hand
      to the left hand. Activation of cerebrum and cerebellum varied according to hand.
      Activation common to both hands occurred in the bilateral dorsal premotor cortex
      and parasagittal cerebellum, right inferior frontal gyms, left lateral cerebellum
      and thalamus, supplementary motor area, and cerebellar vermis. The left lateral
      cerebellum showed the most prominent activation on the first trial of the novel
      task, and hence may be related the early phase of learning, or "what to do"
      learning. Left parasagittal cerebellum activity diminished with training both in
      first and second blocks, correlating inversely with task performance. This region
      may therefore be involved in later learning or "how to do" learning. The activity
      of these regions was less prominent with prior training than without it. Thus the
      left cerebellar hemisphere may be related to learning transfer across hands.

PMID- 15249113
TI  - The effect of chronic lithium on arachidonic acid release and metabolism in rat
      brain does not involve secretory phospholipase A2 or lipoxygenase/cytochrome P450
      pathways.
AB  - The mood-stabilizer lithium, when chronically administered to rats at therapeutic
      concentrations, has been shown to downregulate brain arachidonic acid (AA)
      turnover and total phospholipase A2 (PLA2) activity, as well as protein and mRNA
      levels of cytosolic cPLA2. These effects are accompanied by a decrease in
      cyclooxygenase (COX)-2 protein level, COX activity, and brain prostaglandin E2
      (PGE2) concentration. The involvement of Ca2+-dependent secretory PLA2 (sPLA2) in
      the mechanism of action of lithium has not been investigated. The purpose of this
      study was to examine, whether the effect of lithium is selectively directed to
      cPLA2 or it also affects sPLA2 protein and enzyme activity and whether other AA
      metabolizing enzymes (5-lipoxygenase and cytochrome P450 epoxygenase) were also
      altered. Furthermore, to determine if the reduction of brain PGE2 concentration
      was due only to downregulation of COX-2 protein or if it also involves the
      terminal PGE synthase, we determined brain microsomal PGE synthase protein level.
      Male Fischer-344 rats were fed lithium chloride for 6 weeks, whereas, control
      rats were fed lithium-free chow under parallel conditions. We found that chronic
      lithium did not significantly change sPLA2 activity or protein level. 5
      Lipoxygenase and cytochrome P450 epoxygenase protein levels were unchanged, as
      were levels of the terminal PGE synthase. These results indicate that the effect
      of lithium selectively involves the cPLA2/COX-2 pathway, which might be
      responsible for the therapeutic effect in bipolar disorder.

PMID- 15249114
TI  - Taurine administration during lactation modifies hippocampal CA1
      neurotransmission and behavioural programming in adult male mice.
AB  - Taurine plays a role in neuronal development. In this study, we examined whether
      postnatal taurine administration influences the long-term consequences induced by
      mild neonatal stressors (10 min maternal deprivation plus sham injection, applied
      daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed
      higher pain threshold both in the tail-flick--which measures mostly the spinal
      mechanisms of pain--and in the hot-plate test--which reflects mainly the
      supraspinal mechanisms of pain. The latter effect was prevented completely by
      neonatal taurine administration, while the tail-flick test was not affected, thus
      suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of
      age, mice which were stressed during the neonatal period showed consistent
      decrease in immobility time in forced swimming test, and taurine did not
      influence this parameter. At the same age, the fear/anxiety axis, measured with
      elevated plus maze test, did not show any consistent changes.
      Electrophysiological experiments in brain slices obtained from adult mice showed
      that input-output curves in hippocampal CA1 were increased by taurine
      administration in lactation. Hence, neonatal administration of taurine might
      permanently modify the functioning of hippocampus, a brain area which is known to
      be crucial for learning and memory.

PMID- 15249115
TI  - Localization of G protein-coupled receptor kinases (GRKs) in the avian retina.
AB  - G protein-coupled receptor kinases (GRKs) are enzymes involved in agonist
      dependent regulation of G protein-coupled receptors. In the present work, we
      characterized, by immunohistochemistry, the presence of GRKs 2, 3 and 5 in the
      chick retina, a tissue whose structure and neurochemistry are well known. These
      enzymes are expressed in specific cell types and regions of the retina.
      Immunoreactivity for GRK2 was found over photoreceptor inner segments, cell
      bodies of horizontal, amacrine and ganglion cells. Labeling for this enzyme was
      also observed over the two plexiform layers. Immunoreactivity for GRK3 was found
      in cell bodies of amacrine and ganglion cells. In plexiform layers, specific GRK3
      immunoreactivity was observed only at the inner plexiform layer, where three
      bands of high labeling were detected. In contrast to GRK2 and 3, intense
      immunoreactivity for GRK5 was observed only over Muller cells. Occasionally,
      labeled amacrine cell bodies were also observed. These results suggest that GRKs
      2, 3 and 5 are expressed and involved in the physiology of specific cells types
      of the retina. They also suggest that receptor-GRK specificity may be determined
      by the co-expression of the receptor and the kinase within individual cell
      populations in this tissue.

PMID- 15249116
TI  - Effects of electroacupuncture on orphanin FQ immunoreactivity and preproorphanin
      FQ mRNA in nucleus of raphe magnus in the neuropathic pain rats.
AB  - Orphanin FQ (OFQ) is an endogenous ligand for opioid receptor-like-1 (ORL1)
      receptor. Previous studies have shown that both OFQ immunoreactivity and
      preproorphanin FQ (ppOFQ) mRNA expression could be observed in the brain regions
      involved in pain modulation, e.g., nucleus of raphe magnus (NRM), dorsal raphe
      nucleus (DRN), and ventrolateral periaqueductal gray (vlPAG). It was reported
      that electroacupuncture (EA) has analgesic effect on neuropathic pain, and the
      analgesic effect was mediated by the endogenous opioid peptides. In the present
      study, we investigated the effects of EA on the changes of OFQ in the neuropathic
      pain rats. In the sciatic nerve chronic constriction injury (CCI) model, we
      investigated the changes of ppOFQ mRNA and OFQ immunoreactivity in NRM after EA
      by in situ hybridization (ISH) and immunohistochemistry methods, respectively.
      Then, the ppOFQ mRNA-positive and OFQ immunoreactive cells were counted under a
      computerized image analysis system. The results showed that expression of ppOFQ
      mRNA decreased and OFQ immunoreactivity increased after EA treatment in the
      neuropathic pain rats. These results indicated that EA modulated OFQ synthesis
      and OFQ peptide level in NRM of the neuropathic pain rats.

PMID- 15249117
TI  - Alterations in the central vasopressin and oxytocin axis after lesion of a brain
      osmotic sensory region.
AB  - The anteroventral region of the third ventricle (AV3V) is critical in mediating
      osmotic sensitivity. AV3V lesions increase plasma osmolality and block osmotic
      induced vasopressin (VP) and oxytocin (OT) secretion. The aim was to evaluate the
      effects of AV3V lesions on neurosecretion under control/water replete conditions
      and after 48 h dehydration. The focus was on central peptidergic changes with
      measurement of OT and VP content in the hypothalamic paraventricular (PVN) and
      supraoptic (OT) regions and the posterior pituitary. AV3V-lesioned rats exhibited
      an elevated plasma osmolality and higher OT content in SON and PVN. There was an
      increase in VP content in PVN, but no change in SON. As predicted, the plasma
      peptide response to dehydration was absent in lesioned animals. However,
      dehydration produced depletion in posterior pituitary VP in lesioned animals with
      no change in OT. No changes in nuclear VP and OT levels were seen after
      dehydration. These results demonstrate that AV3V lesions alter the VP and OT
      neurosecretory system, seen as a blockade of osmotic-induced release and an
      increase in basal nuclear peptide content. The data indicate that interruption of
      the osmotic sensory system affects the central neurosecretory axis, resulting in
      a backup in content and likely changes in synthesis and processing.

PMID- 15249118
TI  - Effects of repeated restraint stress on hypothalamo-pituitary-adrenocortical
      function in vasopressin deficient Brattleboro rats.
AB  - Arginine-vasopressin (AVP) has been proposed to be an important mediator during
      chronic stress in the regulation of the hypothalamo-pituitary-adrenal axis. In
      the present study we addressed the role of AVP in maintaining adrenocortical
      responsiveness during chronic stress using the AVP deficient mutant Brattleboro
      rat. Heterozygous Brattleboro rats (di/+) served as controls and were compared to
      homozygous rats (di/di) with diabetes insipidus. Sixty minutes daily restraint
      was repeated for 5, 8, 11 or 15 days and organ weights, plasma
      adrenocorticotropin (ACTH) and corticosterone levels and anterior pituitary
      proopiomelanocortin (POMC) mRNA and ACTH content were measured. The body, adrenal
      and thymus weight changes induced by chronic stress became significant between 5
      and 8 repetition and AVP deficiency had no effect on these parameters. The first
      indication that AVP has a role to play appears after 11 repetitions. In the di/di
      group at the end of 11th restraint, the plasma ACTH was decreased when compared
      to the di/+ rats. In animals with indwelling cannulas some adaptation could be
      seen in ACTH response without any difference between di/+ and di/di rats after 15
      restraints. The corticosterone- and prolactin-elevations induced by restraint did
      not habituate in the di/+ and the di/di rats. Chronic stress increased POMC mRNA
      in the anterior pituitary similarly in di/+ and di/di rats. Although AVP seems to
      be necessary for a full ACTH response, most of the other signs of chronic stress
      after repeated restraint occur unchanged in the absence of AVP in both genders.
      This suggests that either AVP is not indispensable for activating the hypothalamo
      pituitary-adrenocortical system by chronic stress or the absence of AVP is
      compensated by other mediators in Brattleboro rats.

PMID- 15249119
TI  - GABA(B) receptor activation in the suprachiasmatic nucleus of diurnal and
      nocturnal rodents.
AB  - Diurnal (day-active) and nocturnal (night-active) animals have very different
      daily activity patterns. We recently demonstrated that the suprachiasmatic
      nucleus (SCN) responds to GABAergic stimulation differently in diurnal and
      nocturnal animals. Specifically, GABAA receptor activation with muscimol during
      the subjective day causes phase delays in diurnal grass rats while producing
      phase advances in nocturnal hamsters. The aim of the following experiments was to
      determine if diurnal and nocturnal animals differ in their response to GABAB
      receptor activation in the SCN. Baclofen, a GABAB receptor agonist, was
      microinjected into the SCN region of grass rats or hamsters under free-running
      conditions and phase alterations were analyzed. Changes in phase were not
      detected after baclofen treatment during the subjective day in either grass rats
      or hamsters. During the night, however, GABAB receptor activation significantly
      decreased the ability of light to induce phase delays in grass rats. Taken
      together with previous data from our laboratory, these results demonstrate that,
      in both hamsters and grass rats, GABAB receptor activation in the SCN
      significantly affects circadian phase during the night, but not during the day.

PMID- 15249120
TI  - Roles for prostaglandins in the steroidogenic response of human granulosa cells
      to high-density lipoproteins.
AB  - In human granulosa-lutein cells, high-density lipoproteins (HDL) can stimulate
      progesterone synthesis. The objective of the present study was to establish
      whether prostaglandins (PGs) participate in the steroidogenic response to HDL.
      Both HDL and apolipoprotein AI (ApoAI) stimulated concentration-dependent
      increases in PGE2, cAMP and progesterone accumulation. The minimum concentrations
      of HDL and ApoAI required to elevate PGE2 production were the same as those
      required to stimulate cAMP accumulation and progesterone synthesis.
      Concentrations of PGE2 were elevated within 10 min in cells exposed to HDL and
      rose progressively over 24 h, whereas cAMP and progesterone were only increased
      significantly after 24 h of treatment with HDL. Co-treatment with prostaglandin H
      synthase inhibitors (meclofenamic acid and indomethacin) abolished the cAMP and
      progesterone responses to both HDL and ApoAI. Hence, the ability of HDL to
      stimulate progesterone synthesis can be mimicked by ApoAI and appears to involve
      increased generation of one or more luteotrophic PGs, possibly acting via cAMP.

PMID- 15249121
TI  - Angiotensin II-stimulated cortisol secretion is mediated by phospholipase D.
AB  - Angiotensin II (Ang-II) regulates a variety of cellular functions including
      cortisol secretion. In the present report, we demonstrate that Ang-II activates
      phospholipase D (PLD) in zona fasciculata (ZF) cells of bovine adrenal glands,
      and that this effect is associated to the stimulation of cortisol secretion by
      this hormone. PLD activation was dependent upon extracellular Ca2+, and was
      blocked by inhibition of protein kinase C (PKC). Using the reverse transcription
      polymerase chain reaction technique, we demonstrated that ZF cells express both
      PLD-1 and PLD-2 isozymes. Primary alcohols, which attenuate the formation of
      phosphatidate (the product of PLD), and cell-permeable ceramides, which inhibit
      PLD potently, blocked Ang-II-stimulated cortisol secretion. Furthermore,
      propranolol or chlorpromazine, which are potent inhibitors of phosphatidate
      phosphohydrolase (PAP) (the enzyme that produces diacylglycerol from
      phosphatidate), also blocked cortisol secretion. These data suggest that the
      PLD/PAP pathway plays an important role in the regulation of cortisol secretion
      by Ang-II in ZF cells.

PMID- 15249122
TI  - Gene expression by the anterior pituitary gland: effects of age and caloric
      restriction.
AB  - Biological aging is associated with functional deficits at the cellular, organ,
      and system levels. The pituitary gland, the central organ of the neuroendocrine
      system, has been shown to play an important role in the aging process. To gain a
      better understanding of its functional changes with aging, we compared the gene
      expression profiles of the anterior pituitary of young and old Brown Norway rats,
      focusing on the major pituitary hormone genes. We also explored the effects of
      caloric restriction, an intervention shown to delay or inhibit age-associated
      pathologic and biologic changes in a number of systems and organisms, on the
      expression of these genes. Of the total of 1176 genes arrayed on each of the six
      membranes per group that we used, 542 (46%) were detectable in the anterior
      pituitary of young and old rats. Significance analysis of microarrays (SAM) of
      these 542 detectable genes revealed 28 genes that changed significantly with age,
      among which 24 decreased and 4 increased. Among the five major hormone genes on
      the membrane, growth hormone (GH) and prolactin decreased with age, the
      glycoprotein hormone common alpha subunit gene increased, and follicle
      stimulating hormone-beta subunit (FSH-beta) and thyrotropin-beta (TSH-beta)
      subunit did not change. Among these genes, the three found to change by array
      analysis were confirmed to do so by Northern blot analysis. For the two genes
      among the five that were not selected (i.e. did not change) by array analysis,
      TSH-beta also showed no significant change by Northern blot; but the other, FSH
      beta, showed significant increase. Thus, of the five genes checked by Northern
      blot analysis, the results were consistent with the array data in four cases.
      Short-term caloric restriction (5 weeks) of young adult animals resulted in 19
      genes being significantly down-regulated, while no significantly up-regulated
      genes were identified. Among the genes that were down-regulated were GH,
      gonadotropin releasing hormone receptor (GnRH-R), three cytochrome c oxidase
      subunits and two heat shock proteins. With long-term (21 month) caloric
      restriction, about 30% of the genes that changed with aging (8/28) were prevented
      from doing so, and none of the age-related changes was enhanced with long-term
      caloric restriction. The genes that showed most significant rescue were
      neuropeptide Y, GnRH-R, DNA-binding protein inhibitor Id-3, and nerve growth
      factor-induced protein I-B. These results indicate that long-term caloric
      restriction can partially prevent some of the age-related changes in gene
      expression in the anterior pituitary of Brown Norway rats, suggesting a benefit
      of this regimen to be the slowing of the aging process. The fact that fewer than
      30% genes derived benefit also suggests that the effect of caloric restriction is
      rather limit, which is consistent with the thesis that caloric restriction may
      slow, but not prevent, the aging process.

PMID- 15249123
TI  - Regulation of human glucocorticoid receptor gene transcription by Sp1 and p53.
AB  - The human glucocorticoid receptor (hGR) gene has several GC boxes in the promoter
      1C region. We studied the effects of Sp1 and p53 on promoter 1C in HepG2 and
      HEK293 cells using luciferase (Lu) reporter assay. The results showed that the
      first GC box upstream of the transcription site activated the hGR promoter and
      over-expression of Sp1 obviously enhanced the activity. A mutant Lu-hGR vector,
      whose first GC box was defective, lost promoter activity nearly completely.
      Further, over-expression of p53 strongly suppressed the stimulating effect of Sp1
      on hGR promoter activity. We concluded that Sp1 activates the hGR gene promoter,
      at least in part, by acting on the first GC box in promoter 1C, while p53
      suppresses the transactivation by Sp1. These phenomena, demonstrated in cultured
      cells, may be important for the expression of hGR in vivo.

PMID- 15249124
TI  - hSrb7, an essential human Mediator component, acts as a coactivator for the
      thyroid hormone receptor.
AB  - Nuclear hormone receptors interact with the basal-transcriptional complex and/or
      coactivators to regulate transcriptional activation. These activator-target
      interactions recruit the transcriptional machinery to the promoter and may also
      stimulate transcriptional events subsequent to the binding of the machinery to
      the promoter or enhancer element. We describe a novel functional interaction of
      the nuclear thyroid receptor (TR), with a human Mediator component (hSrb7), and a
      human TFIIH component (hMo15). In mammalian two-hybrid experiments as well as in
      GST-pull down assays, hSrb7 interacts with TR but not with other nuclear
      receptors such as the retinoic acid receptor (RAR) or the vitamin D receptor
      (VDR). Whereas hMo15 also interacts with VDR and RAR in mammalian two-hybrid
      assays, no association of hSrb7 with VDR or RAR is found. Accordingly,
      cotransfection of TR and hSrb7 increases thyroid hormone (T3)-dependent
      transcription in an AF-2-dependent manner, while hSrb7 causes no stimulation of
      vitamin D- or retinoic acid-mediated transactivation. These results reveal a
      novel co-activator role for hSrb7 and hMo15 on TR transcriptional responses, and
      demonstrate that different receptors can selectively target different co
      activators or general transcription factors to stimulate transcription.

PMID- 15249125
TI  - Screening of FSH receptor gene in Argentine women with premature ovarian failure
      (POF).
AB  - Diverse mutations in FSH-receptor (FSHR) gene have been described as possible
      cause of premature ovarian failure (POF). To investigate the presence of
      mutations and/or polymorphisms in FSHR gene, DNA from 20 POF, 5 of which were
      diagnosed as resistant ovary syndrome (ROS), and from 44 controls was isolated
      from peripheral lymphocytes. The complete coding sequence was analysed by PCR
      followed by SSCP, direct sequencing or restriction enzyme analysis. No mutations
      in FSHR gene were identified in the patients studied. The two already described
      polymorphisms in exon 10, A919G and A2039G, cosegregated in all the homozygous
      individuals, indicating that FSHR presents two isoforms: Ala307-Ser680 and Thr307
      Asn680. OR results suggest that the 919G-2039G allelic variant or the homozygous
      genotype is not associated to disease risk. In addition, a heterozygous
      substitution T1022C (Val341Ala) was found in two control subjects. We suggest
      that mutations in FSHR gene are rare in women with POF in Argentine. Presence of
      a particular FSHR isoform does not appear to be associated with this disease.

PMID- 15249126
TI  - Cell-specific expression of betaC-activin in the rat reproductive tract, adrenal
      and liver.
AB  - betaC-activin expression was assessed in rat tissues, using reverse transcription
      and real-time polymerase chain reaction, Western blotting and
      immunohistochemistry with a specific monoclonal antibody. betaC-activin mRNA was
      predominantly expressed in liver, but significant amounts were found in rat whole
      pituitary extracts (n = 5), and in three of five extracts of ovary, testis, and
      adrenal gland. Specific betaC-activin immunoreactivity was demonstrated in the
      cytoplasm of hepatocytes, neurosecretory cell terminals in posterior pituitary,
      ovarian primordial follicles, theca interna, large luteal cells and rete ovarii,
      spermatogonia, pachytene spermatocytes and Leydig cells of the testis, uterine
      endometrium, oviduct epithelium and zona glomerulosa of the adrenal. The
      observation of stage-specific expression in gonadal cells suggests this activin
      subunit has specific roles, different from those of other activin/inhibin
      subunits. Small amounts of mRNA in the presence of significant betaC-activin
      protein highlights the importance of examining betaC-activin expression at both
      the mRNA and protein level.

PMID- 15249127
TI  - Testosterone enhances calcium reabsorption by the kidney.
AB  - The kidney is a target tissue for androgens, but the role of these hormones in
      the regulation of calcium (Ca2+) reabsorption remains unclear. The present study
      examines the effects of testosterone on Ca2+ transport by the luminal membranes
      of proximal and distal nephrons of the rabbit kidney. Tubule suspensions were pre
      incubated in the presence or absence of the hormone, and 45C2+ uptake by the
      luminal membranes was measured using the rapid filtration technique. In the
      proximal tubules, testosterone did not influence Ca2+ uptake. In the distal
      tubules, a 5 min incubation with the hormone increased this uptake with a maximal
      response at 10(-10)M. Ca2+ transport by the distal membranes shows a dual
      kinetics. Testosterone enhanced the Vmax value of the low affinity component. In
      an attempt to identify the underlying mechanisms involved in this action, several
      messenger inhibitors were introduced in the tubule suspension. PD 98059 and U0
      126 as well as AG 99 and genistein interfered with the hormone action suggesting
      the implication of a MEK kinase and a tyrosine kinase. To determine the type of
      the channels involved in this effect, Ca2+ uptake was measured in the presence of
      diltiazem, omega-conotoxin MVIIC and mibefradil, i.e. selective inhibitors of the
      L-type, P/Q type and T-type channels. An inhibition of Ca2+ transport was
      observed exclusively with mibefradil. These results indicate that testosterone
      enhances Ca2+ transport by opening a T-type Ca2+ channel in the distal luminal
      membrane, via MEK kinase and tyrosine kinase dependent mechanisms.

PMID- 15249128
TI  - Id2 is a primary partner for the E2-2 basic helix-loop-helix transcription factor
      in the human placenta.
AB  - We screened a term placental cDNA library by the yeast two-hybrid approach with
      Id2, a negative regulator of basic helix-loop-helix (bHLH) factors. Of the clones
      obtained, approximately one-third were the E2-2 bHLH transcription factor. Id2
      and E2-2 were shown to interact in direct two-hybrid assays in yeast cells, as
      well as immunoprecipitation assays in mammalian cells. Immunohistochemical
      analysis demonstrated co-localization of both Id2 and E2-2 in placental
      trophoblasts. Co-transfection of JEG-3 cells with E2-2 and Id2, and a luciferase
      reporter construct under the control of the human chorionic gonadotropin alpha
      subunit promoter revealed that E2-2 had a negative effect on CGalpha-subunit
      transcription, which could be relieved by overexpression of Id2. The library was
      in turn rescreened with E2-2, and Id2 and Id1 were essentially the only clones
      obtained. We conclude that Id2 is a primary binding partner for the bHLH
      transcription factor E2-2 in the human placenta.

PMID- 15249129
TI  - Immunohistochemical localization of inducible and endothelial nitric oxide
      synthase in porcine ovaries and effects of NO on antrum formation and oocyte
      meiotic maturation.
AB  - The present study is to investigate the immunolocalization of endothelial and
      inducible nitric oxide synthase (eNOS, iNOS) in porcine ovary and the effect of
      nitric oxide (NO) on antrum formation and oocyte meiotic resumption. In
      Experiment 1, preantral follicles (250-300 microm in diameter) were cultured in 0
      (Control), 0.1, 0.3, 0.5 or 1 mM sodium nitroprusside (SNP), a NO donor. In
      Experiment 2, the cumulus-oocyte complexes (COCs) aspirated from medium follicles
      (3-6 mm in diameter) were incubated in 0.1mM SNP or two inhibitors for NOS, 10 mM
      aminoguanidine bicarbonate salt (AG) or 1 mM Nomega-nitro-l-arginine methyl ester
      (L-NAME), alone or concomitantly. In Experiment 3, ovarian tissues, corpus luteum
      (CL), corpus albican (CA) and COCs from small (1-2 mm in diameter), medium (3-6
      mm) and large follicles (7-10 mm) were isolated, rinsed, fixed, paraffin embedded
      and stained by the conventional avidin-biotin complex method for the detection of
      eNOS and iNOS production. The results showed that 0.1mM SNP had no effect on
      antrum formation (P > 0.05) while 0.3, 0.5 or 1 mM significantly inhibited the
      antrum formation (P < 0.05). AG markedly inhibited porcine oocyte meiotic
      resumption (P < 0.05) while L-NAME inhibited first polar body (PB1) extrusion (P
      < 0.05). The immunoreactivity of eNOS in early antral follicles was restricted to
      oocyte and it increased from small, medium to large follicle-enclosed oocytes.
      Cumulus cells from large follicles showed weak eNOS immunoreactivity but those
      from small or medium follicles not. In CL, eNOS-positive staining was shown in
      granulosa lutein cells. In CA, it was in some parenchymal cells. In contrast, no
      immunoreactivity for iNOS was found in primordial, early antral follicle or the
      COCs aspirated from small and medium follicles. The large follicle-enclosed
      oocyte showed weak immunoreactivity. In CL, some granulosa lutein cells showed
      iNOS-positive cytoplasm. Such immunostaining was not found in CA. The results
      demonstrate that porcine ovaries have distinct cell-specific expression of both
      eNOS and iNOS, and that NO derived from both NOS is actively involved in meiotic
      resumption. Nitric oxide is not involved in the antrum formation of preantral
      follicles but exogenous NO inhibits the antrum formation. Endothelial nitric
      oxide synthase and inducible nitric oxide synthase might be differently
      functional in CL development and regression.

PMID- 15249130
TI  - Molecular cloning and endometrial expression of porcine high density lipoprotein
      receptor SR-BI during the estrous cycle and early pregnancy.
AB  - During rapid development of the fetus, levels of high density lipoprotein (HDL)
      are elevated in pregnant women. The receptor for HDL, scavenger receptor class B
      type I (SR-BI), mediates selective cholesteryl ester uptake and is highly
      expressed in the human placenta. Because of the rapid growth of uterus during
      early pregnancy and differences in placentation between swine and humans, we
      hypothesized that SR-BI may be expressed in porcine endometrium to take up HDL
      cholesterol. The objectives of this study were to obtain the full coding region
      for porcine SR-BI, determine endometrial expression of SR-BI mRNA during the
      estrous cycle and early pregnancy, and map the gene. By iterative screening of a
      porcine expressed sequence tag library, we obtained the full coding region of SR
      BI. Endometrial expression of SR-BI in White composite gilts (n = 3-4 each) was
      determined by Northern blotting on Days 10, 13, and 15 cyclic gilts and Days 10,
      13, 15, 20, 30, and 40 pregnant gilts. In cyclic gilts, endometrial expression of
      SR-BI did not change between Days 10 and 13, but increased (P < 0.01) between
      Days 13 and 15. In pregnant gilts, endometrial expression of SR-BI increased (P <
      0.01) between Days 10 and 13, remained elevated until Day 30, and decreased (P =
      0.015) on Day 40. The SR-BI gene was mapped to 46.3 cM on chromosome 14. These
      results show that endometrial expression of SR-BI changes during the estrous
      cycle and early pregnancy, and suggest that SR-BI takes up HDL for endometrial
      development during early pregnancy.

PMID- 15249131
TI  - Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol
      synthesis in immature mouse testes by two pathways.
AB  - 5alpha-Androstane-3alpha,17beta-diol (androstanediol) is the predominant androgen
      in immature mouse testes, and studies were designed to investigate its pathway of
      synthesis, the steroid 5alpha-reductase isoenzyme involved in its formation, and
      whether testicular androstanediol is formed in embryonic mouse testes at the time
      of male phenotypic development. In 24-26-day-old immature testes, androstanediol
      is formed by two pathways; the predominant one involves testosterone -->
      dihydrotestosterone --> androstanediol, and a second utilizes the pathway
      progesterone --> 5alpha-dihydroprogesterone --> 5alpha-pregnane-3alpha-ol-20-one 
      -> 5alpha-pregnane-3alpha,17alpha-diol-20-one --> androsterone -->
      androstanediol. Formation of androstanediol was normal in testes from mice
      deficient in steroid 5alpha-reductase 2 but absent in testes from mice deficient
      in steroid 5alpha-reductase 1, indicating that isoenzyme 2 is not expressed in
      day 24-26 testes. The fact that androstenedione and testosterone were the only
      androgens identified after incubation of day 16 and 17 embryonic testes with
      [3H]progesterone implies that androstanediol formation in the testis plays no
      role in male phenotypic differentiation in the mouse.

PMID- 15249132
TI  - Steroid hormonal regulation of growth, prostate specific antigen secretion, and
      transcription mediated by the mutated androgen receptor in CWR22Rv1 human
      prostate carcinoma cells.
AB  - CWR22Rv1 (22Rv1) is an androgen-responsive human prostate carcinoma cell line
      derived from a primary prostate tumor that expresses mutant (H874Y) androgen
      receptors (AR) and secretes low levels of prostate specific antigen (PSA). In
      this study, we examined the effects of various androgens and other steroid
      hormones on proliferation of 22Rv1 cells, PSA secretion, and transactivation.
      Incubation of 22Rv1 cells with various concentrations of testosterone resulted in
      a dose-dependent 50-80% increase in growth over 72 h. PSA release and
      transactivation of PRE2-tk-LUC in 22Rv1 cells were stimulated by low
      concentrations of natural and synthetic androgens (EC(50)s = 10(-10) to 10(-9)M)
      and a broad range of other classes of steroid hormones, albeit with lower
      potency. Uniform positive immunocytochemical staining was observed in 22Rv1 cell
      nuclei with mouse monoclonal antibodies to human AR. Competitive binding assays
      indicated that the mutant AR in 22Rv1 cytosol is more promiscuous than a wild
      type AR (ARLBD: rat AR ligand binding domain). Testosterone (10(-8)M)-induced PSA
      release and transactivation were blocked by both antiandrogens and antiprogestins
      with IC(50)s of 10(-7) to 10(-6)M. At high concentration (10(-6)M), these
      antagonists showed partial agonist activity in terms of PSA secretion but not
      transactivation. In conclusion, the mutant AR in 22Rv1 cells binds and responds
      to low levels of androgens and a wide spectrum of other natural and synthetic
      steroid hormones, mechanisms proposed to contribute to tumor progression
      following androgen ablation.

PMID- 15249133
TI  - Activity of the hippocampal somatostatinergic system following daily
      administration of melatonin.
AB  - If melatonin or its analogs are to be used therapeutically in humans, their
      chronic effects on responsiveness of melatonin target cells need to be assessed.
      We have previously demonstrated that acute melatonin treatment regulates the
      somatostatinergic system in the rat hippocampus. In the present study, we have
      investigated the effects of subchronic and chronic daily treatment with melatonin
      on the somatostatinergic system in the rat hippocampus. Male Wistar rats (200-250
      g) were injected with melatonin (25 microg/kg body weight, subcutaneously) daily
      for 4, 7 or 14 days and sacrificed 24 h after the last injection. Melatonin
      administration for 4 days induced a decrease in the hippocampal somatostatin
      (SRIF)-like immunoreactivity content as well as a decrease in the number of SRIF
      receptors and an increase in their apparent affinity. The decreased number of
      SRIF receptors in the melatonin (4 days)-treated rats was associated with a
      decreased capacity of SRIF to inhibit both basal and forskolin-stimulated
      adenylyl cyclase activity. These melatonin-induced effects reversed to control
      values after 7 or 14 days of treatment. Hippocampal membranes from control and
      melatonin-treated rats showed similar Gi and Gs activities. Melatonin treatment
      altered neither the functional Gi activity nor the Gialpha 1 or Gialpha 2 levels
      at any of the time periods studied. The present results suggest that chronic
      exposure to melatonin results in a tolerance of the hippocampus to this hormone.

PMID- 15249134
TI  - Calcium influx pathways in rat CNS pericytes.
AB  - In central nervous system (CNS), pericytes have been proposed to play a role in
      broad functional activities including blood-brain barrier, microcirculation, and
      macrophage activity. However, contractile responses and Ca2+ signaling in CNS
      pericytes have not been elucidated. The aim of the present study is to
      investigate contractility and Ca2+ influx pathway in CNS pericytes. CNS pericytes
      were cultured from rat brain. Contraction of the pericytes in response to various
      stimuli was evaluated by the change in surface area measured by a light
      microscope with a digital camera. Reverse transcription and polymerase chain
      reaction (RT-PCR) was performed to examine the expression of mRNA of alpha-smooth
      muscle actin. Intracellular Ca2+ was measured using fura-2 fluorescence
      spectroscopy. A23187 (Ca2+ ionophore), high external K+ (4 x 10(-2) mol/l),
      endothelin-1, and serotonin induced contraction of CNS pericytes. RT-PCR analysis
      revealed the expression of alpha-smooth muscle actin in CNS pericytes. Cytosolic
      Ca2+ ([Ca2+]i) increased after application of high concentration of external K+,
      tetraethylammonium, and charybdotoxin, which was inhibited by nicardipine and
      removal of external Ca2+. Angiotensin-II, serotonin, acetylcholine, ATP, and
      endothelin-1 caused biphasic response in [Ca2+]i. In response to these agents,
      [Ca2+]i rapidly increased and then decayed to a relatively constant Ca2+ plateau.
      The Ca2+ plateau was partially inhibited by nicardipine and completely abolished
      by omission of external Ca2+. After intracellular Ca2+ store was depleted by the
      removal of external Ca2+ and addition of thapsigargin, reapplication of external
      Ca2+ evoked increases in [Ca2+]i. These results indicate that CNS pericytes
      express mRNA of alpha-smooth muscle actin and possess contractile ability. In CNS
      pericytes, resting membrane potential is regulated by large conductance Ca2+
      activated K+ channels and Ca2+ enters into the cells via L-type voltage-dependent
      Ca2+ channels, agonist-activated Ca2+ permeable channels, and capacitative Ca2+
      entry pathways.

PMID- 15249135
TI  - High affinity binding of Dab1 to Reelin receptors promotes normal positioning of
      upper layer cortical plate neurons.
AB  - The positions of neurons in the neocortex, hippocampus, cerebellum and various
      other laminated brain regions are regulated by a signaling pathway initiated by
      the secreted protein Reelin and requiring the intracellular adaptor protein Dab1.
      Dab1 and the Reelin receptors VLDLR and ApoER2 are expressed by neurons whose
      migrations are coordinated by Reelin. In vitro, Dab1 binds with high affinity to
      the cytoplasmic tails of VLDLR and ApoER2 via its PTB domain. To test the
      importance of Dab1 binding to VLDLR and ApoER2, we replaced the Dab1 gene with a
      cDNA cassette encoding a point mutant allele, Dab1(F158V). This mutation strongly
      decreases Dab1 binding in vitro to peptides containing the ApoER2 or VLDLR
      cytoplasmic regions. Surprisingly, Dab1(F158V/F158V) homozygotes have no
      discernable phenotype. However, Dab1(F158V/-) hemizygous animals have a subtle
      phenotype in which late-generated cortical plate neurons migrate excessively into
      the marginal zone. Early cortical plate neurons, subplate neurons, hippocampal
      pyramidal cells and cerebellar Purkinje cells are positioned normally. Thus
      Dab(F158V) is a weak loss-of-function (hypomorphic) allele that has no detectable
      effect when homozygous. The phenotype of Dab1(F158V/-) hemizygotes shows that
      late cortical plate neurons of layers 2-3 require efficient Reelin-Dab1 signaling
      to prevent them entering the marginal zone. The Dab1(F158V) allele adds to a
      series of Dab1 alleles that demonstrates cell type-specific variation in the
      Reelin-Dab1 pathway.

PMID- 15249136
TI  - Expression of myelencephalon-specific protease in transient middle cerebral
      artery occlusion model of rat brain.
AB  - Myelencephalon-specific protease (MSP) is one of the serine proteases and is
      expressed in the central nervous system of rats. Its function and alternation in
      brain injury have not yet been clarified. In this study, we investigated the
      expression of MSP after transient middle cerebral artery occlusion (MCAO) using
      in situ hybridization and immunohistochemistry. In situ localization of MSP mRNA
      demonstrated a higher level in the corpus callosum and around the ischemic area
      from 12 h to 14 days after MCA reperfusion, with the peak of expression coming 3
      days after reperfusion in both regions. Immunohistochemically, the expression of
      protein was found 1 day after reperfusion in the same brain region that was
      observed for mRNA. The peak was 7 days after reperfusion in both regions. Micro
      autoradiography, immunostaining and double immunohistochemical labeling revealed
      the expression of MSP to be located mainly in the oligodendrocytes. The present
      results indicate that MSP may be related to the turnover of the myelin-associated
      proteins and the extracellular matrix proteins after transient MCAO. The
      activation of MSP may play a role in remodeling processes such as neurite
      outgrowth and remyelination.

PMID- 15249137
TI  - Chronic cerebral hypoperfusion and reperfusion injury of restoration of normal
      perfusion pressure contributes to the neuropathological changes in rat brain.
AB  - Restoration of normal perfusion pressure after resection of cerebral
      arteriovenous malformations (AVMs) is sometimes complicated by unexplained
      postoperative brain swelling and/or intracranial hemorrhage, which has been
      termed normal perfusion pressure breakthrough (NPPB). The precise mechanism of
      NPPB is still unclear. In this study, we investigated the time courses of blood
      brain barrier (BBB) disruption, water content, neuronal apoptosis,
      myeloperoxidase (MPO) activity and superoxide dismutase (SOD) activity in the
      brain during restoration of normal perfusion pressure in a new rat model of
      chronic cerebral hypoperfusion associated with AVMs. Male Sprague-Dawley rats
      were randomly divided into either a sham-operated group, a control group, or a
      model group with reperfusion assessed at 1, 12, 24 and 72 h after restoration of
      normal perfusion pressure. BBB disruption was judged by extravasation of Evans
      blue (EB) dye. We observed that EB and water content in rat brains of the model
      group with reperfusion were significantly increased compared with the other
      groups. The most predominant increase occurred at 1 h after reperfusion, and the
      next at 24 h after reperfusion, representing biphasic changes which are similar
      to the pathological processes of acute cerebral ischemia/reperfusion injury.
      There was no difference of the percentage of apoptotic cells in rat brains
      between the sham-operated group and the control group using flow cytometry. No
      prominent apoptotic cells were found in the model group with reperfusion at 1 h.
      However, the percentage of apoptotic cells increased significantly in rat brains
      of the model group with reperfusion at 12 h, peaked at 24 h, and decreased at 72
      h after reperfusion. Apoptotic cells were confirmed with electron microscopy and
      terminal deoxynuleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL). A significant enhancement of MPO activity in combination with reduction
      of SOD activity was seen at 12, 24 and 72 h in rat brains of the model group with
      reperfusion. Our data indicates that reperfusion after restoration of normal
      perfusion pressure with chronic cerebral hypoperfusion lead to secondary neuronal
      damage which may associate with cerebral ischemia/reperfusion injury.

PMID- 15249139
TI  - Nerve growth factor induces elevation of steroid 5alpha-reductase mRNA levels in
      rat C6 glioma cells through expression of transcription factor Egr-1.
AB  - Steroid 5alpha-reductase type 1 (5alpha-R), the enzyme converting progesterone
      and other steroid hormones to their 5alpha-reduced metabolites, has been shown to
      be localized in both neuronal and glial cells, and this enzyme in glial cells has
      previously been reported to be activated either by co-culturing with neuronal
      cells or by adding the conditioned medium of neuronal cells, thus suggesting that
      neuronal activity may be implicated in the regulation of neurosteroid metabolism
      in brain. In the present study, to investigate a potential role of neurotrophic
      factors in the mechanism regulating the production of neuroactive 5alpha-reduced
      steroid metabolites, the direct action of NGF on 5alpha-R gene expression was
      examined by measuring the steady-state levels of 5alpha-R mRNA levels in rat C6
      glioma cells. Exposure of the glioma cells to NGF increased both 5alpha-R mRNA
      and its protein levels, and induced the transient elevation of Egr-1 mRNA levels
      prior to the expression of 5alpha-R mRNA in the cells. Furthermore, NGF failed to
      induce any significant elevation of 5alpha-R mRNA levels in the cells pretreated
      with Egr-1 antisense oligodeoxynucleotides. These findings indicate that NGF
      induces the elevation of 5alpha-R gene expression in the glioma cells through the
      expression of transcription factor Egr-1, proposing the possibility that NGF, and
      probably other neurotrophic factors as well, may play a potential role in the
      regulation of 5alpha-reduced steroid production as one of the factors mediating
      the intercellular communication between neuronal and glial cells in the brain.

PMID- 15249138
TI  - Inhibitors of protein phosphatase-2A: topography and subcellular localization.
AB  - The mRNA and protein expressions of I1(PP2A) and I2(PP2A), the two inhibitors of
      protein phosphatase 2A (PP2A) were investigated in adult rat brain. The rat brain
      and human brain inhibitors showed similar molecular weights by Western blots. The
      cDNA probes for human brain I1(PP2A) and I2(PP2A) readily hybridized with the
      corresponding mRNAs of rat brain inhibitors in Northern blots. We detected 3.7
      and 2.1 kb transcripts of I1(PP2A) and 2.9 and 2.0 kb transcripts of I2(PP2A) in
      rat brain. In situ hybridization revealed that the mRNAs of the two inhibitors
      were mainly localized in neurons. Strong expression of both I1(PP2A) and I2(PP2A)
      mRNAs were observed in the olfactory bulb, hippocampal pyramidal and dentate
      granule cell layers, and cerebellar Purkinje cell, granular and molecular layers.
      Moderate expression of I1(PP2A) and I2(PP2A) mRNAs were observed in the cerebral
      cortex, caudate putamen, thalamus, hypothalamus, amygdala and pontine nucleus.
      The expression of I1(PP2A) and I2(PP2A) and as well as of PP-2A was also
      investigated by immunohistochemistry using antibodies to each protein. The
      distribution patterns of the two inhibitor proteins were similar to those of
      their corresponding mRNAs and to the expression of PP-2A. While PP-2A was
      localized to neuronal perikarya, I1(PP2A) was observed both in the neuronal
      cytoplasm and the nucleus. I2(PP2A) had mainly nuclear localization but it could
      also be seen in the neuronal cytoplasm. All three proteins were also expressed in
      the neuropil. These studies suggest that PP-2A activity is probably regulated by
      I1(PP2A) and I2(PP2A) in the adult mammalian central nervous system, and that
      these inhibitors are conserved between rat and human brains.

PMID- 15249140
TI  - DHEA and DHEA sulfate differentially regulate neural androgen receptor and its
      transcriptional activity.
AB  - The mechanism of action of dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEA-S), two interconvertable neurosteroids, has
      not been fully characterized in the central nervous system (CNS). Previous
      studies demonstrated that DHEA was intrinsically androgenic, suggesting that it
      may act through a genomic pathway. However, it is not known whether DHEA-S also
      produces androgenic effects, an important question given that the concentration
      of DHEA-S in brain is some 7-12 times that of DHEA. The current study compared
      the potential androgenic effects of DHEA-S with DHEA by examining their capacity
      to induce two characteristic effects of an androgenic compound. These included
      the ability to (1) up-regulate neural androgen receptor (AR) protein level in
      mouse brain and immortalized GT1-7 hypothalamic cells and (2) assess their effect
      on reporter gene expression through AR in CV-1 cells cotransfected with pSG5-AR
      and pMMTV-ARE-CAT reporter. Semi-quantitative Western blot analysis showed that
      DHEA treatment significantly augmented AR in mouse brain and GT1-7 cells in a
      dose-dependent manner and that these effects were not blocked by trilostane
      (TRIL), a known 3beta-hydroxysteroid dehydrogenase inhibitor. DHEA also promoted
      AR-mediated reporter gene expression as a function of dose and the effect was
      comparable with or without the addition of TRIL. In contrast, DHEA-S treatment
      failed to increase AR level in the mouse brain or GT1-7 cells and modestly
      induced AR-mediated reporter gene expression only at substantially elevated
      concentrations compared to DHEA. The findings demonstrate that DHEA is capable of
      exerting androgenic effects through AR while the androgenicity of DHEA-S is
      negligible. The implications of the results for models of the mechanism of action
      of DHEA and its sulfate ester, DHEA-S, in the brain are considered.

PMID- 15249141
TI  - Rat tyrosine hydroxylase promoter directs tetracycline-inducible foreign gene
      expression in dopaminergic cell types.
AB  - A prerequisite for creating animal models in which gene expression is spatially
      and temporally controlled is the development of promoters to target genetic
      switches to specific populations of cells. Here we used the dopaminergic
      biosynthetic enzyme, tyrosine hydroxylase (TH) to test various combinations of
      tetracycline (Tet) system elements to determine the optimal configuration for
      inducible, tissue-specific expression. The present study shows that the degree of
      expression and level of leakiness associated with the Tet transactivators rtTA,
      rtTA2S-M2, tTS/rtTA or tTS/rtTA2S-M2 was dependent upon both the promoter and
      cell type utilized. Specifically, CMV-driven tTS/rtTA2S-M2 exhibited the highest
      level of inducibility in HEK cells (approximately 1000-fold) versus the
      dopaminergic cell line, MN9D (approximately 70-fold). In contrast, TH-driven
      rtTA2S-M2 yielded the highest level of expression with the least background in
      dopaminergic cell types versus HEK cells. Moreover, the TH promoter could be
      combined with the bi-directional Tet response system, BiTetO, allowing for the co
      expression and regulation of two genes in the same cell. To further test the
      feasibility of this system we replaced the reporter gene with human Bcl-2.
      Consistent with previous studies, induction of Bcl-2 expression in dopaminergic
      cell types attenuated cell death due to the neurotoxin, MPP+. Taken together,
      these data suggest that targeted, inducible gene expression can be achieved in
      dopaminergic cell types.

PMID- 15249142
TI  - Increased CRE-binding activity and tryptophan hydroxylase mRNA expression induced
      by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rat frontal cortex
      but not in the hippocampus.
AB  - A single administration of either 3,4-methylenedioxymethamphetamine (MDMA,
      "ecstasy") or p-chloroamphetamine (PCA) produced a rapid and marked reduction of
      serotonin (5-HT) content in rat frontal cortex and hippocampus. In the cortex of
      MDMA-treated rats, 5-HT levels returned to control values 48 h after drug
      administration. This recovery was correlated with an induction of CRE-binding
      activity and an enhanced expression of tryptophan hydroxylase (TPH) mRNA, the
      rate-limiting enzyme in 5-HT biosynthesis, suggesting that MDMA may up-regulate
      the TPH gene through a CREB-dependent mechanism. In the cortex of PCA-treated
      rats, neither a recovery of 5-HT levels nor changes in DNA-binding or TPH mRNA
      were found at the same time point. In the hippocampus of rats receiving either
      PCA or MDMA a decrease in TPH mRNA levels was found at all times, along with a
      reduced CRE-binding at the 8-h time point. The results show region-specific
      effects of MDMA. In the frontal cortex, the increased TPH expression suggests a
      compensatory response to MDMA-induced loss of serotonergic function.

PMID- 15249143
TI  - Nicotinic and muscarinic acetylcholine receptors are essential for the long-term
      response of tyrosine hydroxylase gene expression to chronic nicotine treatment in
      rat adrenal medulla.
AB  - Nicotine induces tyrosine hydroxylase (TH) mRNA by interacting with nicotinic
      acetylcholine receptors (nAChRs) in cultured adrenal medullary cell systems;
      however, the mechanisms responsible for the induction of adrenal TH in response
      to systemically administered nicotine under in vivo conditions are more complex.
      In the present study, we tested whether nAChRs and muscarinic acetylcholine
      receptors (mAChRs) participate in the induction of adrenal TH observed after long
      term treatment with nicotine. Chronic nicotine treatment (1.6 mg/kg, two daily
      injections spaced 12 h apart for 7 days) induced TH mRNA, TH protein and TH
      activity in rat adrenal medulla. This induction of TH gene expression was totally
      blocked when an antagonist of either nAChRs or mAChRs was administered prior to
      each nicotine injection. Repeated injections of the mAChR agonist bethanechol (5
      mg/kg injected twice per day for 7 days) also produced increases in TH mRNA
      levels; however, TH protein levels and TH activity did not increase in response
      to bethanechol. In denervated adrenal glands chronic nicotine treatment did not
      lead to induction of either TH mRNA, TH protein or TH activity, whereas chronic
      bethanechol treatment led to induction of TH mRNA, but not TH protein or
      activity. These results suggest that agonist occupation of both nAChRs and mAChRs
      are essential for the complete response of TH gene expression to chronic nicotine
      treatment in rat adrenal medulla, but that stimulation of either cholinergic
      receptor by itself is not sufficient to elicit a full response. The results also
      suggest that both transcriptional and post-transcriptional mechanisms may
      potentially need to be regulated to induce TH protein in response to some
      stimuli.

PMID- 15249144
TI  - From wild wolf to domestic dog: gene expression changes in the brain.
AB  - Despite the relatively recent divergence time between domestic dogs (Canis
      familiaris) and gray wolves (Canis lupus), the two species show remarkable
      behavioral differences. Since dogs and wolves are nearly identical at the level
      of DNA sequence, we hypothesize that the two species may differ in patterns of
      gene expression. We compare gene expression patterns in dogs, wolves and a close
      relative, the coyote (Canis latrans), in three parts of the brain: hypothalamus,
      amygdala and frontal cortex, with microarray technology. Additionally, we
      identify genes with region-specific expression patterns in all three species.
      Among the wild canids, the hypothalamus has a highly conserved expression
      profile. This contrasts with a marked divergence in domestic dogs. Real-time PCR
      experiments confirm the altered expression of two neuropeptides, CALCB and NPY.
      Our results suggest that strong selection on dogs for behavior during
      domestication may have resulted in modifications of mRNA expression patterns in a
      few hypothalamic genes with multiple functions. This study indicates that rapid
      changes in brain gene expression may not be exclusive to the development of human
      brains. Instead, they may provide a common mechanism for rapid adaptive changes
      during speciation, particularly in cases that present strong selective pressures
      on behavioral characters.

PMID- 15249145
TI  - Mutation analysis of the Sonic hedgehog promoter and putative enhancer elements
      in Parkinson's disease patients.
AB  - Sonic hedgehog (SHH) is involved in the induction and differentiation of
      nigrostriatale dopaminergic neurons. We have investigated the promoter, two
      putative enhancer elements and the coding region of SHH for mutations in patients
      with Parkinson's disease (PD). None of the identified sequence variations were
      present at a significantly different frequency in PD patients compared to healthy
      individuals, suggesting that they are not involved in the pathogenesis of PD.

PMID- 15249146
TI  - Circuit training for elderly patients with chronic obstructive pulmonary disease:
      a preliminary study.
AB  - To examine the efficacy of the circuit training in elderly patients with chronic
      obstructive pulmonary disease (COPD), we evaluated muscle forces of the upper and
      lower extremities and respiratory muscles, exercise tolerance and quality of life
      (QOL) before and after the circuit training in 10 male patients with mild to
      severe COPD. The circuit training improved muscle forces of the upper and lower
      extremities and abdominal muscles (P < 0.05), and 6 min walking distance (P <
      0.05). Emotional function and mastery in the Chronic Respiratory Disease
      Questionnaire scores (P < 0.05) were also improved after the circuit training.
      The circuit training designed in the present study was effective to improve the
      QOL in elderly COPD patients.

PMID- 15249147
TI  - Pneumonia in elderly patients with preexisting respiratory disease.
AB  - To evaluate the optimal duration of appropriate antibiotic therapy for pneumonia
      in elderly patients with preexisting respiratory disease, we studied improvement
      of infectious parameters in these patients. The medical record database was used
      to identify patients admitted with the following characteristics: primary
      diagnosis of benign respiratory disease; aged 65 years or over; no active
      malignant diseases in any organs; and at least one admission for pneumonia during
      April 2001 to May 2003. We observed 47 pneumonia episodes in 30 patients.
      Elevated CRP levels more than 8.0 mg/ml and leukocytosis more than 10.0 x 10(3)
      mm(-3) was seen in 21 and 29 pneumonia episodes, respectively. With appropriate
      intravenous antimicrobial therapy, average of CRP levels on day 0 (9.16 +/- 6.81
      mg/dl) decreased to 5.18 +/- 4.67 mg/dl on day 3 (P = 0.0073). In more than 70%
      of pneumonia episodes, serum levels of CRP normalized on day 10. Average of
      leukocyte counts on day 0 ((12.3 +/- 4.7) x 10(3) mm(-3)) decreased to (8.1 +/-
      3.5) x 10(3) mm(-3) on day 3 (P = 0.0001). In more than 80% of pneumonia
      episodes, leukocyte count normalized on day 7. The clinical response to
      appropriate antimicrobial therapy for pneumonia occurs within the first 3 days of
      therapy. Duration of intravenous antimicrobial therapy for pneumonia in these
      patients of 10 days would be sufficient and could prevent recurrent infection
      with resistant bacteria.

PMID- 15249148
TI  - Triple task Clock Completion Test (CCT) as a predictor of functional outcome in
      geriatric rehabilitation.
AB  - Cognitive status is considered as a predictor of the rehabilitation outcome. The
      triple task Clock Completion Test (CCT), which evaluates visuospatial skill, has
      been demonstrated to be a sensitive predictor of functional capacity. The
      objective of the study was to test the predictive validity of the CCT for
      assessing functional outcome in geriatric rehabilitation. Functional evaluation
      using the Functional Independence Measure (FIM) and cognitive evaluation using
      the Mini Mental State Examination (MMSE) as well as the CCT, were performed in 77
      elderly patients (35 men, 42 women, median age 81.5 years) on admission and
      discharge. Significant positive coefficients of correlation were found between
      the admission and discharge CCT scores, and negative coefficients, between CCT
      and FIM scores, both on admission and discharge. CCT and MMSE scores correlated
      significantly just on admission. The MMSE and the FIM scores were significantly
      higher among those who succeeded than in those who failed on the CCT in the task
      of setting the hour on admission and discharge, whereas in the task of reading
      the hour, just on admission. The triple task CCT is a sensitive tool for
      identifying cognitive impairment affecting the executive functions and an
      important functional outcome predictor.

PMID- 15249149
TI  - The effect of electric stimulation treatment on the functional rehabilitation of
      acute geriatric patients with stroke--a preliminary study.
AB  - The most common neurological damage in acute stroke/cerebrovascular accident
      (CVA) is a decline in the senso-motor capacities of both the upper and the lower
      extremities with a more severe injury in the upper ones. Motor improvement of the
      affected limb can be attained through frequent intensive exercise by electrical
      stimulation (ES). The objective of this study was to examine the effect of the ES
      treatment using Handmaster ES device on the functional rehabilitation of elderly
      patients after acute CVA. Twenty-two elderly with different levels of damage and
      partial movements in their upper limb joints underwent a 3-week treatment. Nine
      of them were treated for additional 3-weeks after a 3-week break. After the first
      3-week treatment, significant improvements were observed, in all the subjects, in
      the active range of motion (ROM) of the shoulder and the wrist joints, on manual
      dexterity tests and on functional independence measure (FIM). After the two
      periods of treatment the nine subjects exhibited significant improvements in ROM
      and in manual dexterity. FIM score increased by the same rate after each of the
      three stages. This preliminary study has proven that the Handmaster treatment can
      improve the geriatric rehabilitation outcome of elderly patients with senso-motor
      deficit caused by acute CVA.

PMID- 15249150
TI  - Folate status and folate related anemia: a comparative cross-sectional study of
      long-term care and post-acute care psychogeriatric patients.
AB  - Aging is associated with increased risk of anemia, poor nutrition, chronic
      illness, and impaired folate status. We aimed to investigate and compare folate
      status in long-term care psychogeriatric patients (LTCPP) and in post-acute care
      psychogeriatric patients (PACPP). This is a cross-sectional study conducted in a
      psychogeriatric medical center with long-term care and post-acute care wards. A
      total number of 553 LTCPP and 373 PACPP were studied. Low serum folic acid levels
      were found in 10% of LTCPP and in 13% of PACPP. Folic acid anemia (FAA) was found
      in 67% of LTCPP and 87% of PACPP (P = 0.046) with low serum folate levels. Mean
      levels of serum folate were similar but red blood cells folate (RBC-folate) was
      higher in PACPP (P = 0.025) and in males compared with women (P = 0.009). 56% of
      PACPP and 68% of LTCPP who had folic acid anemia presented with another type of
      anemia. Anemia of chronic disease was the most frequent coexisting anemia and was
      found in 65% of LTCPP and 52% of PACPP, followed by B12 deficiency anemia and
      iron deficiency anemia. We conclude that PACPP represent only a slightly
      different group, compared with LTCPP, with regard to the folate status. These
      high rates of folate and RBC-folate deficiencies, as well as of FAA and
      coexisting anemia, call for a routine evaluation of folate status in all
      psychogeriatric patients, whether LTCPP or PACPP.

PMID- 15249151
TI  - Cognitive status and development in the oldest old: a longitudinal analysis from
      the Heidelberg Centenarian Study.
AB  - In the present study, we investigated cognitive status, cognitive development and
      the effect of mortality on cognitive changes in very old age. Analyzing data from
      the population-based Heidelberg Centenarian Study, results revealed that
      centenarians differed quite strongly in their cognitive capacities. While about
      half of the population showed moderate to severe cognitive impairment, one
      quarter was found to be cognitively intact. Moreover, analyzing cognitive change
      over a period of 1.5 years, centenarians' cognitive performance was revealed to
      be rather stable. Finally, only a small effect of mortality on cognitive status
      and changes was detected, supporting a recent hypothesis that the terminal
      decline or drop in cognitive functioning decreases in very old age.

PMID- 15249152
TI  - Relationship between low back pain in post-menopausal women and mineral content
      of lumbar vertebrae.
AB  - Until recently, chronic low back pain in post-menopausal women was commonly
      attributed to osteoporosis. This opinion has since been challenged on many
      counts, but controversy persists. The objective of this study was to examine this
      relationship. In 67 post-menopausal women, the mineral content of the lumbar
      vertebrae was measured by dual-energy X-ray absorptiometry and the age-normalized
      bone mineral index (ANBMI), the Z-score, was determined. Mean ANBMI in 40
      subjects who complained of chronic low back pain (Group 1) was compared with mean
      ANBMI in the 27 who did not (Group 2). Pain intensity and related disability were
      quantified using standard questionnaires. Their respective correlations with
      ANBMI index and age at onset of menopause were examined. Correlation coefficients
      and significance of group differences were examined by appropriate statistical
      methods. The results showed that the mean ANBMI in Group 1 subjects was 96.5 +/-
      16.9%, in Group 2 subjects it was 88.6 +/- 10.0%. Neither pain intensity nor
      disability was correlated with ANBMI. A weak but significant positive correlation
      was noted between body mass index and intensity of low back pain (r = 0.37; P <
      0.05). The occurrence and severity of chronic low back pain in post-menopausal
      women, and the disability thereof, appear to be unrelated to the mineral content
      of lumbar vertebrae.

PMID- 15249153
TI  - Postural stability in the elderly: empirical confirmation of a theoretical model.
AB  - The study investigated whether physiological factors related to specific body
      systems can explain postural control as measured by the scalar distance at a
      given time between the center of pressure (COP) and the center of mass (COM), the
      COP-COM variable. The data from 46 healthy subjects and 29 subjects with
      disabilities due to stroke or diabetic peripheral neuropathy were analyzed. The
      biomechanical variable COP-COM was determined using two force platforms and an
      optoelectric system. Three systems were considered as possible predictors of the
      COP-COM amplitude: sensory (somatosensory and vision), musculoskeletal and
      central processor. A confirmatory analysis was done using structural equation
      modeling. Strength explained 23.74% of the COP-COM amplitude in the antero
      posterior (A/P) with eyes open (EO) condition, and in the medio-lateral (M/L)
      direction strength explained 40.73 and 28.75% in the EO and eyes closed (EC)
      respectively. In the A/P direction with EC, 51.75% of the COP-COM amplitude
      variance was explained mainly by the somatosensory system. This study highlight
      the role of peripheral somatosensory input and muscle strength in the maintenance
      of postural stability during quiet stance in the elderly. The indirect action of
      the different systems on the COP-COM amplitude supports the systems theory.

PMID- 15249154
TI  - The effect of the timing of hip fracture surgery on the activity of daily living
      and mortality in elderly.
AB  - The optimal time for the operation of hip fractures in elderly is not clear. Most
      of the data indicate that early operation is associated with better prognosis and
      improved health quality. We aimed to investigate the effect of timing of surgical
      intervention on the frequency of post-operative complications, recovery of weight
      bearing ability, total hospitalization time and activities of daily living (ADL)
      scores. Sixty five patients subjected to surgical repair were followed up. All
      were evaluated for their ADL before fracture, post-operative 1st, 3rd, 6th and
      12th month. The patients operated within 5 days after hospitalization constituted
      the early group (n = 38, 24 females, 14 males; mean age = 76.16 +/- 7.08 years),
      and the patients operated after the fifth day served as the late group (n = 27,
      18 females, 9 males; mean age = 75.81 +/- 7.50). Time of recovery of weight
      bearing ability and total hospitalization time were significantly higher in the
      late group (P < 0.05). ADL scores in 1st, 3rd and 6th month after surgery were
      significantly lower (P < 0.05), and death rates on post-operative 1st and 12th
      month were significantly higher in the late group (P < 0.05). Elderly, operated
      within 5 days of the hip fracture have increased survival time and better life
      quality than those operated after the fifth day of the admission. The data
      supports the previous reports which indicate the necessity of the early operation
      of elderly hip fractures.

PMID- 15249155
TI  - The psychogeriatric and risk behavior assessment scale (PARBAS): a new measure
      for use with older adults living in the community.
AB  - In the context of decreased access to inpatient mental health care, the
      assessment of risk behavior in older adults living in the community is a growing
      concern. The purpose of the study was to develop a risk behavior screening tool
      to help community practitioners plan early intervention for frail older adults
      with severe mental illness (SMI) referred to community health and social service
      centers. The initial instrument development involved discussion-based work among
      practitioners and researchers. It was followed by a content validation phase
      (involving nine experts), preliminary testing of inter-rater reliability (27
      subjects, 12 pairs of raters), and item analysis procedures combining previous
      data. The psychogeriatric and risk behavior assessment scale (PARBAS) includes 34
      items organized in 10 sections of risk behavior: (i) self neglect; (ii) non
      compliance; (iii) substance abuse; (iv) risk toward oneself and others; (v)
      aggressive behavior; (vi) emotional distress; (vii) suicidal behavior; (viii)
      personal security; (ix) risk of victimization by others and (x) financial
      security. It can provide professionals with essential information about their
      clients' risky behaviors, thereby contributing to timely and appropriate
      preventive interventions. Future research is needed to establish its psychometric
      properties.

PMID- 15249156
TI  - Characterization of a new synthetic isoflavonoid with inverse agonist activity at
      the central benzodiazepine receptor.
AB  - Research aimed at developing selective drugs acting on gamma-aminobutyric acid
      (GABA)A receptors introduced compounds from diverse chemical classes unrelated to
      the 1,4-benzodiazepines, including flavonoids. These studies also revealed the
      potential use of inverse agonists as cognition-enhancing agents. Here we report
      pharmacological properties of the novel synthetic isoflavonoid 2-methoxy-3,8,9
      trihydroxy coumestan (PCALC36). PCALC36 displaced [3H]flunitrazepam binding to
      rat brain synaptosomes with an IC50 of 13.8 microM. Scatchard analysis of the
      effect of PCALC36 showed a concentration-dependent reduction of the Bmax of
      [3H]flunitrazepam, without a marked change in Kd. This effect could be reversed
      by diluting and washing the preparation. Addition of 20-microM GABA shifted to
      the right the inhibition curve of PCALC36 on [3H]flunitrazepam binding (IC50
      ratio of 0.68), which is characteristic for inverse agonists. PCALC36 produced
      little change in the GABAergic tonic currents recorded by whole-cell patch clamp
      in cultured rat hippocampal neurones, but it caused a 20% reduction in miniature
      inhibitory postsynaptic current amplitude and completely antagonised the full
      (direct) agonist midazolam in a quickly reversible manner. The data suggest that
      the coumestan backbone can be useful for developing novel ligands at the GABAA
      receptor.

PMID- 15249157
TI  - Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at
      human recombinant serotonin 5-HT7 receptors.
AB  - Recombinant 5-hydroxytryptamine 5-HT7 receptors are known to express
      constitutive, i.e., agonist-independent activity. Nonselective ligands, like
      methiothepin, ritanserin or clozapine behave as full inverse agonists at 5-HT7
      receptors. The aim of the present study was to evaluate the degree of inverse
      agonist activity of three selective 5-HT7 receptor antagonists ((R)-3,N-dimethyl
      N-[1-methyl-3-(4-methyl-piperidin-1-yl)propyl]benzene sulfonamide or SB-258719, R
      (+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine or SB
      258741 and (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolidine-1-sulfonyl)
      phenol or SB-269970) in the same model. cAMP accumulation was measured in intact
      Chinese hamster ovary (CHO) cells expressing human recombinant 5-HT7a receptors.
      In these cells, 5-HT stimulated cAMP levels and a series of ligands antagonized
      the effect of 5-HT with a 5-HT7 receptor-like profile. SB-258719 had no inverse
      agonist activity, SB-258741 behaved as a partial inverse agonist and SB-269970
      was a quasi-full inverse agonist (as compared to methiothepin). The inverse
      agonist effect of SB-269970 was antagonized in a concentration-dependent manner
      by SB-258719. The widespread spectrum of inverse agonist activities shown by
      these compounds should help assessing the physiological relevance of constitutive
      5-HT7 receptor activity in native tissues.

PMID- 15249158
TI  - Mood stabilizers inhibit glucocorticoid receptor function in LMCAT cells.
AB  - Mood stabilizers block some central effects induced by stress and
      glucocorticosteroids; however, little is known about interaction of these drugs
      with glucocorticoid receptor function. In the present study, we evaluated effects
      of lithium, valproate and carbamazepine on glucocorticoid receptor-mediated gene
      expression in mouse fibroblast cells (L929), stably transfected with mouse
      mammary tumor virus (MMTV)-chloramphenicol acetyltransferase reporter plasmid
      (LMCAT cells). Treatment of LMCAT cells with lithium (1-4 mM), valproate (0.1-3
      mM) and carbamazepine (30 and 100 microM) inhibited corticosterone-induced
      activity of reporter gene in a time- and concentration-dependent manner.
      Furthermore, it was found that valproate, but not two other antimanic drugs,
      decreased the glucocorticoid receptor level in cytosolic and nuclear fraction,
      and its inhibitory effect on glucocorticoid receptor-mediated transcriptional
      activity was attenuated by c-Jun N-terminal kinase (JNK)-mitogen-activated
      protein kinase (MAPK) inhibitor. Protein kinase B (PKB), glycogen synthase kinase
      (GSK), p38-MAPK and depletion of inositol were not shown to be involved in the
      mechanism of mood-stabilizer action on glucocorticoid receptor function under
      present experimental condition. In contrast to mood stabilizers, amphetamine (1
      100 microM) had no effect on glucocorticoid receptor-mediated transcriptional
      activity. These findings corroborate the hypothesis that direct effects of
      antidepressants and mood stabilizers on glucocorticoid receptor function is an
      important mechanism, by which these drugs may inhibit some deleterious effects of
      stress and glucocorticoids on the central nervous system.

PMID- 15249159
TI  - Protection by cyclosporin A of mitochondrial and cellular functions during a cold
      preservation-warm reperfusion of rat liver.
AB  - Liver transplantation is an effective therapeutic option for end-stage liver
      disease, but initial poor graft function still occurs, often related to cold
      preservation-warm reperfusion (CPWR) conditions. Damages to mitochondria could be
      implicated in hepatocyte cell death since opening of the permeability transition
      pore (PTP) can lead to necrosis and apoptosis. The purpose of this study was to
      test the hypothesis that inhibition of mitochondrial permeability transition by
      cyclosporin A could improve rat liver mitochondrial and hepatocellular parameters
      after 24-h cold preservation followed by a warm reperfusion in Krebs-Henseleit
      Buffer. Mitochondrial functions were assessed by measuring respiratory
      parameters, swelling, cytochrome c release and caspases activation. Hepatocyte
      injury was assessed by evaluation of ATP energetic charge, lactate dehydrogenase
      (LDH) leakage, apoptosis and necrosis. Results show that CPWR induces liver
      mitochondrial and cellular damages. CPWR induced damages on the mitochondrial
      respiratory chain, leading to mitochondrial swelling. The consequences are the
      loss of ATP energetic charge, the initiation of apoptosis through cytochrome c
      release and the activation of caspases. Cyclosporin A partially protects
      respiratory chain integrity and totally prevents mitochondrial swelling, allowing
      better recovery of energetic charge. It also partially limits the activation of
      the apoptotic machinery and subsequent cell death by apoptosis in both the organ
      and isolated hepatocytes. Inhibition of permeability transition thus provides
      only partial protection against CPWR. However, this target can be considered as a
      promising adjunct therapeutic approach to improve the primary function of the
      grafted liver after transplantation.

PMID- 15249160
TI  - The interaction between vigabatrin and diazepam on the electroencephalogram
      during active behaviour in rats: an isobolic analysis.
AB  - To test whether polytherapy with two gamma-aminobutyric acid (GABA) -ergic drugs
      might be clinically relevant for epilepsy treatment, effects on spike and wave
      discharges, the fraction of time spent being behaviourally active, and the
      background electroencephalogram (EEG) during behavioural activity of vigabatrin
      (15-500 mg/kg i.p.) and diazepam (1.25-10 mg/kg i.p.) were compared with their
      combination (dose ratio 1:25) in rats. Isobolic analyses were performed to
      describe the interactions. Unfortunately, no conclusions can be drawn concerning
      the interaction of both drugs on the spike and wave discharge activity because
      the effect of diazepam was shown to be dominant. Only vigabatrin decreased the
      behavioural activity, whereas there was a trend towards a decrease after
      diazepam. All treatments dose dependently increased the power in the beta
      frequency band. Unfortunately, the dose ratio was not optimal to describe the
      interaction. The theta peak frequency was dose dependently decreased after all
      treatments. There was a synergistic interaction between the two drugs on this
      variable. These data support both the idea that an increase in power in the beta
      frequency band can serve as a biomarker for GABAergic inhibition and the
      suggestion that clinically effective anxiolytics decrease the theta peak
      frequency. Furthermore, we show that on different variables, there might be
      different optimal dosage combinations, which might complicate the clinical
      application of polytherapy.

PMID- 15249161
TI  - MD-354 potentiates the antinociceptive effect of clonidine in the mouse tail
      flick but not hot-plate assay.
AB  - Albeit conflicting, evidence suggests that 5-HT3 receptor partial agonists as
      well as alpha2NON-A-adrenoceptor agonists might be involved in antinociception.
      MD-354 (m-chlorophenylguanidine) can be viewed as the first example of a rather
      selective 5-HT3/alpha2B-adrenergic ligand. In a tail-flick test in mice,
      subcutaneous administration of MD-354 doses up to 30 mg/kg did not produce
      antinociception and failed to antagonize the effect of clonidine (ED50=0.5
      mg/kg), but a combination of an inactive de of clonidine (0.25 mg/kg) that
      produced only 13% maximal possible effect (MPE) with an inactive dose of MD-354
      (10 mg/kg, MPE=8%) produced an antinociceptive effect (MPE=83%). In the hot-plate
      assay, neither subcutaneous administration of MD-354 (3 to 30 mg/kg) alone nor in
      combination with clonidine (ED50=0.8 mg/kg) produced an antinociceptive effect.
      MD-354 was demonstrated to potentiate the antinociceptive effect of clonidine in
      the tail-flick assay, but its underlying mechanism remains to be determined.

PMID- 15249162
TI  - Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices.
AB  - In electrically stimulated rat neocortical brain slices preloaded with [3H]gamma
      aminobutyric acid (GABA) or [3H]glutamic acid, the pharmacological actions of 1
      (aminomethyl)-cyclohexaneacetic acid (gabapentin, Gp) were compared with the
      GABAB receptor agonists baclofen (Bac) and (3-amino-2-(S)-hydroxypropyl)
      methylphosphinic acid (CGP 44532). Gabapentin, baclofen and CGP 44532 all reduced
      the electrically stimulated release of [3H]glutamic acid (IC50=20 microM, 0.8
      microM and 2 microM, respectively). These effects were sensitive to the GABAB
      receptor antagonists (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) or
      N-3-[[1-(S)-(3,4-dichlorophenyl)ethyl]amino]-2-(S)-hydroxypropyl-P-(cyclo
      hexylmethyl)-phosphinic acid (CGP 54626). By contrast, gabapentin was without
      effect on the release of [3H]GABA, whilst baclofen (IC50=8 microM) and CGP 44532
      (IC50=1 microM) inhibited [3H]GABA release. It is concluded that gabapentin
      selectively activates presynaptic GABAB heteroreceptors, but not GABAB
      autoreceptors, and may be a useful ligand to discriminate between presynaptic
      GABAB receptor subtypes.

PMID- 15249163
TI  - Accelerating sensory recovery after sciatic nerve crush: non-selective versus
      melanocortin MC4 receptor-selective peptides.
AB  - Melanocortin receptor ligands accelerate functional recovery after peripheral
      nerve crush. It is not known which mechanism is involved or via which
      melanocortin receptor this effect occurs, albeit indirect evidence favours the
      melanocortin MC4 receptor. To test whether the melanocortin MC4 receptor is
      involved in the effects of melanocortins on functional recovery, we used
      melanocortin compounds that distinguish the melanocortin MC4 receptor from the
      melanocortin MC1, MC3 and MC5 receptors on basis of selectivity and
      agonist/antagonist profile. Activation and binding studies indicated that the
      previously described peptides JK1 (Ac-Nle-Gly-Lys-D-Phe-Arg-Trp-Gly-NH2) and [D
      Tyr4]melanotan-II ([D-Tyr4]MTII. Ac-Nle-c[Asp-His-D-Tyr-Arg-Trp-Lys]NH2) are
      selective for the rat melanocortin MC4 receptor as compared to the rat
      melanocortin MC3 and MC5 receptors, but are also potent on the melanocortin MC1
      receptor. Both peptides did not accelerate sensory recovery in rats with a
      sciatic nerve crush, whereas the non-selective melanocortin agonist melanotan-II
      (MTII, Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]NH2) was effective. The melanocortin
      MC3/MC4 receptor antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2)-Arg-Trp-Lys]NH2)
      also enhanced sensory recovery. This effect was probably not due to interaction
      with the melanocortin MC4 receptor, since JK46 (Ac-Gly-Lys-His-D-Nal(2)-Arg-Trp
      Gly-NH2), a selective melanocortin MC4 receptor antagonist, was ineffective.
      Taken together, these data suggest that melanocortins do not accelerate sensory
      recovery via interaction with the melanocortin MC4 receptor. From the known
      melanocortin receptors, only the involvement of the melanocortin MC5 receptor in
      acceleration of recovery could not be excluded.

PMID- 15249164
TI  - Effect of systemic administration of D-serine on the levels of D- and L-serine in
      several brain areas and periphery of rat.
AB  - To obtain further insight into the distribution and metabolism of exogenous D
      serine, we have investigated the effect of the intraperitoneal administration of
      D-serine (10 mmol/kg) on the concentrations of D- and L-serine in several brain
      areas and periphery of infant and adult rats. The administration produced a
      significant augmentation of the D-serine levels not only in the cortex but also
      in the hippocampus, striatum, cerebellum and periphery. The rapid decline in the
      enhanced D-serine levels was observed in the periphery and cerebellum, whereas
      the injection caused a prolonged elevation of the D-serine levels in the cortex
      and hippocampus. The application caused a slight increase in the L-serine levels
      in several brain areas and periphery 3 or 6 h after the injection, whereas a
      significant decrease in the L-serine concentration was observed in the periphery,
      diencephalon and cerebellum 3 or 7 days after the injection. Because a structural
      abnormality and N-methyl-D-aspartate (NMDA) receptor hypofunction has been
      demonstrated in the cortex and hippocampus of schizophrenic subjects, D-serine
      treatment may offer a new therapeutic approach to diseases related to the
      hypofunction of NMDA receptors such as schizophrenia.

PMID- 15249165
TI  - Evaluation of antipruritic effects of several agents on scratching behavior by
      NC/Nga mice.
AB  - We investigated the effects of several agents on the established itching model in
      NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related
      characteristics. The number of spontaneous scratching behaviors (the duration
      time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before
      and after administration of agents for 24 h. The scratching behavior by NC/Nga
      mice was significantly suppressed by administration of dexamethasone or
      tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride.
      These results suggest that this method shows a good correlation with the
      effectiveness of drugs prescribed for itching in humans with atopic dermatitis,
      and histamine and serotonin do not play an important role in causing the
      scratching behavior seen by NC/Nga mice. The scratching behavior was also
      significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These
      results suggest that the scratching behavior seen in this model is caused by
      itching signal transmission through neural system. Furthermore, we found that
      theophylline, pinacidil or limaprost had scratching suppression effects in this
      model.

PMID- 15249166
TI  - Stress triggered rise in plasma aldosterone is lessened by chronic nicotine
      infusion.
AB  - The ability of nicotine infusion to modulate plasma aldosterone levels in
      response to different stressors was investigated. Sprague-Dawley rats given
      nicotine (5 mg/kg/day) or saline for 14 days were subjected to stress. Baseline
      plasma aldosterone (86+/-17 pmol/l) was unaffected by nicotine. Aldosterone was
      significantly elevated by restraint (450+/-72 pmol/l) and especially with cold
      (1249+/-172 pmol/l) or immobilization (1779+/-247 pmol/l) stress. Nicotine
      infusion attenuated the rise in aldosterone with restraint and cold stress, but
      not immobilization. These results reveal that nicotine infusion can attenuate the
      aldosterone response, depending on the type of stress.

PMID- 15249167
TI  - Vasopressin effects on the coronary circulation after a short ischemia in
      anesthetized goats: role of nitric oxide and prostanoids.
AB  - To examine the coronary effects of arginine-vasopressin during reperfusion after
      a short ischemia, left circumflex coronary artery flow was electromagnetically
      measured, and 15 min total occlusion of this artery followed by reperfusion was
      induced in anesthetized goats (five nontreated, five treated with the inhibitor
      of nitric oxide synthesis Nomega-nitro-L-arginine methyl ester (L-NAME) and five
      treated with the inhibitor of cyclooxygenase meclofenamate). The vasoactive drugs
      and L-NAME were intracoronarily injected, and meclofenamate by i.v. route. At 60
      min of reperfusion, coronary vascular conductance was not changed significantly
      in nontreated and was decreased by 35% (P<0.01) in L-NAME-treated and by 30%
      (P<0.01) in meclofenamate-treated animals. During reperfusion, the coronary
      vasodilatation with acetylcholine (3-100 ng) and sodium nitroprusside (1-10
      microg) was not altered in nontreated animals, and the vasodilatation with
      acetylcholine but not with sodium nitroprusside was partially decreased in L-NAME
      -but not in meclofenamate-treated animals. The vasoconstriction in response to
      arginine-vasopressin (0.03-0.3 microg) was increased during reperfusion in
      nontreated, was not changed in L-NAME-treated and was decreased in meclofenamate
      treated animals. Therefore, it is suggested that during reperfusion after a short
      ischemia: (1) the coronary vasodilator reserve is preserved; (2) the coronary
      vasodilatation with acetylcholine is also preserved, but in this vasodilatation,
      the role of nitric oxide may be attenuated and prostanoids may be not involved;
      and (3) the coronary vasoconstriction with arginine-vasopressin is increased,
      probably due to both attenuation of the modulatory role of nitric oxide and the
      release of vasoconstrictor prostanoids.

PMID- 15249168
TI  - Raloxifene lowers ischaemia susceptibility by increasing nitric oxide generation
      in the heart of ovariectomized rats in vivo.
AB  - We studied the effects of a 2-week period of oral raloxifene therapy on the
      cardiac level of nitric oxide (NO) and on the susceptibility to angina in
      ovariectomized rats. Ovariectomy decreased the activity of Ca2+-dependent nitric
      oxide synthase (NOS) in the left ventricle, an effect restored by raloxifene (0.2
      5 mg kg(-1) day(-1)) or 17beta-oestradiol (0.3 mg kg(-1) day(-1)). Ovariectomy
      led to a significant ST segment depression after the injection of (1) ornithine
      vasopressin (0.5 IU kg(-1), i.v.) or (2) epinephrine (10 microg kg(-1), i.v.),
      followed 30 s later by phentolamine (15 mg kg(-1), i.v.); both effects were
      reversed by raloxifene or 17beta-oestradiol treatment. Inhibition of nitric oxide
      synthase (with NG-nitro-L-arginine methyl ester [L-NAME]; 5 mg kg(-1), s.c.)
      augmented the ST segment depression in the ovariectomized rat and abolished the
      anti-ischaemic effect of 17beta-oestradiol or raloxifene. Thus, an oestrogen
      deficiency down-regulates the cardiac constitutive nitric oxide synthase, which
      increases the susceptibility of the heart to ishaemia because both actions can be
      blocked by exogenous administration of the natural oestrogen 17beta-oestradiol or
      the selective oestrogen-receptor modulator (SERM) raloxifene. In the present in
      vivo system, raloxifene exerts oestrogen-agonist properties.

PMID- 15249169
TI  - Alterations of beta-adrenoceptor responsiveness in postischemic myocardium after
      72 h of reperfusion.
AB  - To determine the effect of a completely developed reperfused myocardial
      infarction model on beta-adrenoceptor responsiveness, we induced a 90-min
      regional ischemia followed by 72 h of reperfusion in dog hearts. Regional
      myocardial blood flow was determined after 60 min of ischemia using radioactive
      microspheres. beta-adrenoceptor density was reduced in the ischemic endocardium
      (95+/-16 fmol/mg) and epicardium (160+/-13 fmol/mg) compared to the nonischemic
      region (304+/-21 fmol/mg). beta-adrenoceptor density in the ischemic endocardium
      varied with the degree of collateral blood flow measured (r2=0.79, P<0.05); this
      relation was the opposite of that in the ischemic epicardium (r2=0.77, P<0.05).
      Higher levels of tissue catecholamines and G protein-coupled receptor kinase 2
      (GRK2) were observed in the ischemic epicardium as compared to nonischemic
      tissue. Forskolin-induced adenylyl cyclase activities were depressed in both
      ischemic regions as compared to nonischemic region, correlating with a reduction
      in regional myocardial blood flow. Using forskolin stimulation as covariate, no
      difference in isoproterenol-induced adenylyl cyclase activity was identified in
      the different regions. It is concluded that cAMP production induced by beta
      adrenoceptor activation is dependent upon adenylyl cyclase enzyme activity rather
      than beta-adrenoceptor density in the ischemic myocardium. However, the density
      of the beta-adrenoceptor in the viable ischemic regions can be modified by the
      presence of GRK2 and tissue catecholamines, an index of regional sympathetic
      efferent postganglionic nerve terminal activity.

PMID- 15249170
TI  - Evaluation of the rat bladder-derived relaxant factor by coaxial bioassay system.
AB  - The release of bladder-derived relaxant factor in a coaxial bioassay system and
      the effects of reactive oxygen species were studied. After precontraction with
      phenylephrine (10(-6)-3x10(-6)) or 50 mM K+, acetylcholine (10(-8)-10(-3) M)
      induced relaxation in rat anococcygeus muscle mounted within rat bladder in a
      tissue bath. This relaxation was not altered by the removal of the urothelium or
      incubation with tetrodotoxin (10(-6) M). However, bupivacaine (10(-4) M) and
      lidocaine (3 x 10(-4) M) inhibited this response after raising the pH of the
      nutrient solution to 7.8, and oxybuprocaine (10(-4) M) exerted inhibitory effect
      at both physiological pH (7.4) and at pH 7.8. Exposure to electrolysis-generated
      reactive oxygen species or incubation with hydrogen peroxide and pyrogallol did
      not alter the acetylcholine response. Present results indicate that the bladder
      derived relaxant factor does not behave like endothelium-derived hyperpolarizing
      factor, but its release may be associated with tetrodotoxin-resistant Na+
      channels, which are probably in the neurons of the bladder rather than in the
      urothelium or detrusor muscle. Furthermore, reactive oxygen species do not
      interact with this relaxing factor, the exact nature and the physiological
      importance of which, however, remains to be established.

PMID- 15249171
TI  - Antiinflammatory effects of genipin, an active principle of gardenia.
AB  - Genipin, the aglycone of geniposide, is metabolically produced from the
      geniposide in body tissues. The purpose of this study is to clarify some
      pharmacological actions of genipin. Genipin showed concentration-dependent
      inhibition on lipid peroxidation induced by Fe++/ascorbate in rat brain
      homogenate. Genipin exhibited significant topical antiinflammatory effect shown
      as an inhibition of croton oil-induced ear edema in mice. Nitric oxide (NO)
      synthesis by inducible nitric oxide synthase (iNOS) is increased in inflammatory
      diseases and leads to cellular injury. Genipin concentration-dependently (50-300
      microM) inhibited NO production and iNOS expression upon stimulation by
      lipopolysaccharide/interferon-gamma (IFN-gamma) in RAW 264.7, a murine macrophage
      cell line. Genipin markedly blocked lipopolysaccharide-evoked degradation of
      inhibitor-kappaB-beta (IkappaB-beta), indicating that it exhibits inhibitory
      effect on NO production through the inhibition of nuclear factor-kappaB (NF
      kappaB) activation. It was also shown to contain potent antiangiogenic activity
      in a dose-dependent manner, which was detected by chick embryo chorioallantoic
      membrane assay. In summary, we demonstrate that genipin possesses
      antiinflammatory and is a specific hydroxyl radical scavenger. Its antiangiogenic
      and NO production-inhibitory properties are also presented.

PMID- 15249172
TI  - Taurine prevents streptozotocin impairment of hormone-stimulated glucose uptake
      in rat adipocytes.
AB  - Streptozotocin-treated rats were used as models of type 1 diabetes to study the
      effects of dietary taurine on insulin- and adrenergic-stimulated 2-deoxyglucose
      uptake by isolated adipocytes. In addition to the well-established impairment of
      basal and insulin-stimulated 2-deoxyglucose uptakes in adipocytes prepared from
      streptozotocin-diabetic rats, the alpha-(phenylephrine) and beta-(isoproterenol)
      adrenergic stimulations of glucose uptake were also abolished. The insulin
      stimulation of glucose uptake in adipocytes was selectively abolished by the
      phosphatidylinositol 3-kinase inhibitor wortmannin, whereas that by the
      adrenergic agonists, phenylephrine and isoproterenol, was inhibited by prazosin
      and propranolol, respectively. Dietary taurine, 4 weeks before and 4 weeks after
      streptozotocin administration, prevented the loss of both insulin and adrenergic
      agonist stimulations of 2-deoxyglucose uptake, without affecting hyperglycaemia.
      Because insulin and adrenergic activations of glucose transport by adipocytes are
      coupled to different signalling pathways, it is unlikely that these effects of
      taurine are related to these disparate postreceptor mechanisms.

PMID- 15249173
TI  - Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in
      streptozotocin-diabetic rats.
AB  - Calcium dobesilate stabilizes blood-retinal barrier in patients with diabetic
      retinopathy and possesses antioxidant properties in the retinas of rats with
      streptozotocin-induced diabetes, exposed ex vivo to ischemia-reperfusion. Here we
      investigated the action of calcium dobesilate on retinal albumin leakage in
      streptozotocin-diabetic rats, together with relevant in vivo retinal antioxidant
      and permeability markers, i.e., carboxymethyl-lysine-advanced glycation end
      product (CML-AGE) formation and vascular endothelial cell growth factor (VEGF)
      overexpression. Twenty days after streptozotocin administration, diabetic rats
      were treated for 10 days with calcium dobesilate (100 mg/kg/day per os) or
      vehicle. Retinal albumin leakage, CML-AGE formation, and VEGF overexpression were
      evaluated by immunohistochemistry of frozen eye sections. Diabetic rats exhibited
      dramatic increases in: (i) retinal albumin leakage (31% of positive vessels vs.
      0.2% in nondiabetic rats, P<0.008), (ii) CML-AGE retinal occurrence (40+/-3% vs.
      undetectable positive vessels), and (iii) retinal VEGF protein expression (14.6+/
      1.1 vs. 3.5+/-0.5 VEGF-positive spots/field, P<10(-4)). Calcium dobesilate
      significantly reduced: (i) retinal albumin leakage (by 70%, P<0.008), (ii)
      retinal CML-AGEs contents (by 62%, P<0.008), and (iii) retinal VEGF expression
      (by 69.4%, P<0.008). In conclusion, calcium dobesilate orally given to diabetic
      rats markedly reduced retinal hyperpermeability, CML-AGE contents, and VEGF
      overexpression. These results strongly suggest that calcium dobesilate stabilizes
      blood-retinal barrier in diabetic retinopathy via an in situ antioxidant action.
      Further studies in patients are required to confirm such view.

PMID- 15249174
TI  - Stunned myocardium--an unfinished puzzle.

PMID- 15249175
TI  - Angiogenesis and platelets: the clot thickens further.

PMID- 15249176
TI  - Tachycardia-induced remodeling: atria and ventricles take a different route.

PMID- 15249177
TI  - GATA transcription factors in the developing and adult heart.
AB  - During the past decade, emerging evidence has accumulated of different nuclear
      transcription factors in regulation of cardiac development and growth as well as
      in cardiac hypertrophy and heart failure. GATA-4, -5 and -6 are zinc finger
      transcription factors that are expressed in the developing heart and GATA-4 and 
      6 continue expression in the adult cardiac myocytes. GATA-4 and -6 regulate
      expression of several cardiac-specific genes, and during murine embryonic
      development, GATA-4 is essential for proper cardiac morphogenesis. In support of
      this, mutations of gene for GATA-4 or for its cofactors have been associated with
      human congenital heart disease. Pressure overload of the heart in vivo as well as
      hypertrophic stimulation of cardiac myocytes in vitro provide adequate stimulus
      for activation of GATA-4. Activity of GATA-4 transcription factor is subject to
      regulation at the level of gene expression and through post-translational
      modifications of GATA-4 protein. A number of genes induced during cardiac
      hypertrophy possess functional GATA sites in their promoter region and cardiac
      specific overexpression of GATA-4 or -6 leads to cardiac hypertrophy. In
      addition, a pattern of interactions between GATA-4 and its numerous cofactors
      have been identified, showing an increasing complexity in regulatory mechanisms.
      The present review discusses current evidence of the role and regulation of GATA
      transcription factors in the heart, with an emphasis in the GATA-4 and
      development of cardiac hypertrophy.

PMID- 15249178
TI  - An update on the cardiac effects of erythropoietin cardioprotection by
      erythropoietin and the lessons learnt from studies in neuroprotection.
AB  - Erythropoietin (Epo) was once thought to act exclusively in the formation of red
      blood cells. As recently reviewed by Smith et al. [Cardiovasc. Res. 59 (2003) 538
      548], Epo can also act within the cardiovascular system with effects in
      thrombosis and hypertension as well as actions on platelets, vascular endothelium
      and smooth muscle, and myocytes of the heart. Here, the actions of Epo to protect
      neuronal cells of the brain are first evaluated and parallel actions of Epo in
      cardioprotection are then drawn. Thus, with recent reports of Epo receptor (EpoR)
      expression by cardiac myocytes, it could be predicted that Epo initiates direct
      protective signalling events. This is supported by five independent studies
      published in 2003 showing Epo protects cardiac myocytes following
      ischemia/reperfusion. Importantly, these protective actions have been observed in
      vitro and in vivo. The former suggests the direct actions of Epo to prevent
      myocyte death independently of its effects on red blood cell number or cells
      other than cardiac myocytes. The latter demonstrates the potential for Epo in the
      treatment of the heart post-infarction, decreasing the numbers of apoptotic
      myocytes, limiting infarct expansion and attenuating the post-infarct
      deterioration in haemodynamic function. These beneficial effects of Epo should
      stimulate further research into the actions of Epo.

PMID- 15249179
TI  - Stunned peri-infarct canine myocardium is characterized by degradation of
      troponin T, not troponin I.
AB  - OBJECTIVE: Degradation of cardiac troponin I (cTnI) has been proposed to
      represent the underlying molecular mechanism responsible for post-ischemic
      contractile dysfunction of viable but 'stunned' myocardium. However, this concept
      is largely derived from models of brief, sublethal ischemia essentially devoid of
      necrosis, and there is speculation that defects in cTnI may be model-dependent.
      Accordingly, our primary aim was to evaluate the integrity of cardiac troponins
      i.e., cTnI, as well as cTnT and cTnC-in viable but stunned peri-infarct tissue.
      In addition, we addressed the as-yet unexplored issue of whether the profound
      reduction of infarct size evoked by brief preconditioning ischemia (PC) was
      accompanied by a favorable attenuation in ischemia/reperfusion-induced
      degradation of cTnI, cTnT or cTnC in the remaining viable subepicardium. METHODS:
      Anesthetized open-chest dogs received 10 min of PC ischemia or a comparable
      control period, followed by 1 h of sustained coronary occlusion and 3 h of
      reperfusion. Subepicardial biopsies from the center of the soon-to-be ischemic
      territory were obtained at baseline and at 30 min and 3 h post-reflow, and
      myofilament protein integrity (intact cTnI, cTnT and cTnC, as well as degradation
      bands and covalent complexes) were assessed by Western immunoblotting. In
      addition, in all dogs, wall thickening was measured by echocardiography,
      collateral blood flow was assessed during sustained occlusion by injection of
      radiolabeled microspheres, and infarct size was delineated by tetrazolium
      staining. RESULTS: Although PC was, as expected, cardioprotective (infarct size
      of 2 +/- 1% of the risk region vs. 17 +/- 6% in controls; p < 0.05), both control
      and PC groups exhibited profound and comparable contractile dysfunction following
      reflow (mean wall thickening reduced to 20-22% of baseline values). There was,
      however, no significant degradation of cTnI in the viable but stunned, peri
      infarct tissue. We did observe degradation of cTnT in the stunned subepicardium,
      an effect that was attenuated in dogs that received antecedent PC ischemia.
      However, there was no correlation between post-ischemic wall thickening and the
      immunoreactivity of the intact cTnT band, or wall thickening and the intensity of
      the cTnT degradation products. CONCLUSIONS: Our results suggest cTnI degradation
      is not a universal determinant of post-ischemic myocardial stunning. Moreover,
      the dissociation between cTnT degradation and wall thickening argue against a
      direct 'cause-and-effect' relationship between proteolysis of cTnT and acute,
      post-ischemic contractile dysfunction of stunned peri-infarct myocardium.

PMID- 15249180
TI  - Differential role of platelet granular mediators in angiogenesis.
AB  - OBJECTIVES: Platelets contain numerous substances regulating angiogenic response.
      However, the regulatory role of platelets in blood vessel development remains to
      be elucidated. We investigated the comprehensive effect of platelets as a
      cellular system on angiogenesis. METHODS: The following approaches were applied:
      (a) in vitro-aortic ring assay and chemotaxis assay; (b) in vivo-injection of
      platelet-containing matrigel plug subcutaneously into a mouse followed by
      immunohistochemical analysis of angiogenic response. RESULTS: Platelets
      stimulated formation of blood vessels in vitro in the rat aortic ring model via
      VEGF and bFGF, while blocking of platelet factor-4 promoted this effect. Addition
      of platelets to the matrigel followed by its subcutaneous injection into a mouse
      resulted in an intensive migration of fibroblasts into the matrigel as well as
      formation of blood capillaries de novo. This platelet effect was mediated through
      bFGF, VEGF, and heparanase. Furthermore, platelet releasate was found to induce
      endothelial cell chemotaxis. This effect was mediated by a concerted action of
      intraplatelet bFGF, PDGF, VEGF, and heparanase. CONCLUSION: Platelets affect
      different stages of the angiogenic response with a trend to a pro-angiogenic net
      effect despite the presence of angiogenesis inhibitors such as platelet factor 4.
      While a concomitant effect of bFGF and VEGF seemed to be essential for the entire
      process of vessel formation (aortic ring and matrigel models), PDGF and
      heparanase were effective only at the migration stage.

PMID- 15249181
TI  - Differences in atrial versus ventricular remodeling in dogs with ventricular
      tachypacing-induced congestive heart failure.
AB  - BACKGROUND: Congestive heart failure (CHF) causes arrhythmogenic remodeling in
      both atria and ventricles, but differences between atrial and ventricular
      remodeling in CHF have not been well characterized. METHODS AND RESULTS: We
      examined atrial and ventricular tissues from dogs with CHF induced by ventricular
      tachypacing (220-240/min) for 0 (control) or 24 h, or 1, 2 or 5 weeks.
      Histopathology was used to assess apoptosis, fibrosis, white blood cell
      infiltration and cell death, ELISA to measure angiotensin-II concentration and
      Western blot to evaluate protein expression. Ventricular tachypacing-induced CHF
      was associated with substantially more fibrosis in left atrium (maximum 10 +/- 1%
      at 5 weeks) than in left ventricle (0.4 +/- 0.1% at 5 weeks, P < 0.01 versus left
      atrium). Tissue angiotensin-II concentration increased to steady state in atrial
      tissue at 24 h but increased more slowly in left ventricle, with a maximum that
      was significantly higher in atrium than ventricle. Ventricular tachypacing caused
      tissue apoptosis, inflammatory cell infiltration and cell death, with maximum
      changes in left atrium being faster, transient and larger than in left ventricle.
      Mitogen activated protein kinase activation was rapid (within 24 h) in left
      atrium, but smaller and slower (p38, c-Jun N-terminal kinase) or non-significant
      (extracellular signal-related kinase) in left ventricle. The 25-kDa activated
      form of transforming growth factor-beta1, a particularly important profibrotic
      mediator in atrium, increased significantly in left atrium, from 2.6 +/- 0.6
      (control) to 9.2 +/- 1.7 (24 h) and 8.1 +/- 1.8 optical density units (1 week),
      but was not significantly changed in ventricle. CONCLUSIONS: There are
      qualitative and quantitative differences in atrial versus ventricular remodeling
      in experimental ventricular tachypacing-induced CHF, with potentially important
      consequences for understanding underlying mechanisms and developing new
      therapeutic approaches.

PMID- 15249182
TI  - Troponin I protein kinase C phosphorylation sites and ventricular function.
AB  - OBJECTIVE: Cardiac Troponin I (cTnI) phosphorylation by protein kinase C (PKC)
      results in a reduction of maximal actomyosin ATPase activity, an effect that is
      more marked at higher levels of calcium (Ca2+) and is likely to reduce active
      force development. We postulated that there would be greater Ca2+-dependent
      changes in ventricular function in hearts of cTnI transgenic (TG) mice expressing
      mutant troponin I lacking PKC sites compared to wild-type (WT). METHODS: We
      studied left ventricular function in isolated perfused hearts over a wide range
      of left ventricular volumes (Frank-Starling relationships) and mechanical
      restitution at three levels of perfusate Ca2+ (1.5, 2.5, and 3.5 mM). Manganese
      enhanced magnetic resonance imaging (MRI) was used to study in-vivo sarcolemmal
      Ca2+ influx. The phosphorylation status of cTnI was examined by western blot
      analysis. RESULTS: Systolic contractile function in TG mice was altered in a
      calcium-dependent manner such that ventricular contractility was significantly
      greater in TG mice only at 3.5 mM perfusate Ca2+. The relaxation process and
      passive mechanical properties were unaltered in TG mice. Mechanical restitution
      parameters were abnormal in TG mice only at 1.5 mM perfusate Ca2+. In-vivo MRI
      data demonstrated up to 48% reduction in Mn2+-induced contrast enhancement,
      indicating reduced sarcolemmal Ca2+ influx. Western blot analysis indicated
      increased cTnI phosphorylation in TG mice. CONCLUSIONS: (1) TG mice exhibit
      calcium-dependent positive inotropy without slowed relaxation and this phenotype
      is mitigated by concomitant (compensatory) changes of reduced intracellular Ca2+
      and increased phosphorylation of remaining cTnI sites. (2) The contractile
      phenotype in TG mice can be interpreted as an amplification of the normal
      response to changes in cellular Ca2+ observed in WT mice. Thus, PKC
      phosphorylation sites on cTnI play a role in attenuating contractile responses to
      changes in intracellular Ca2+.

PMID- 15249183
TI  - Mechanoenergetic inefficiency in the septic left ventricle is due to enhanced
      oxygen requirements for excitation-contraction coupling.
AB  - OBJECTIVE: Myocardial oxygen consumption (MVO2) in the septic myocardium is
      increased despite reduced left ventricular mechanical work. We investigated the
      mechanism behind this energetic inefficiency in the septic myocardium. METHODS:
      To clarify whether energy consumption in basal metabolism or excitation
      contraction (EC) coupling is elevated in the septic myocardium, we separated MVO2
      used for these two processes. We assessed hemodynamics, left ventricular pressure
      volume area, left ventricular MVO2, myocardial substrate metabolism and the
      inflammatory response in eight control pigs and in eight septic pigs receiving E.
      coli endotoxin. Using cardiopulmonary bypass (CPB), unloaded MVO2 was assessed
      before and after arrest of electromechanical activity using KCl infusions.
      RESULTS: Unloaded MVO2 was significantly higher in the septic group compared to
      the control group (65.7 +/- 12.9 vs. 43.3 +/- 15.1 J.min(-1).100 g LV(-1), p <
      0.005), but basal MVO2 after 5 min KCl arrest was equal in the two groups. No
      difference in mechanical energy consumption or substrate metabolism was observed
      between groups. CONCLUSION: Basal MVO2 in the septic myocardium is not elevated,
      but an increased MVO2 for EC coupling is responsible for the energetic
      inefficiency.

PMID- 15249184
TI  - Defective glycosylation of calsequestrin in heart failure.
AB  - OBJECTIVE: Levels of Ca2+ regulatory proteins have been extensively analyzed in
      cardiomyopathies as possible indices of change in sarcoplasmic reticulum (SR)
      structure and function. Measures of calsequestrin (CSQ), however, a critical
      protein component of the Ca2+ release complex in junctional sarcoplasmic
      reticulum, have provided little or no evidence of underlying dysfunction. We
      previously reported that calsequestrin isolated from heart tissue exists in a
      variety of glycoforms and phosphoforms reflecting mannose trimming of N-linked
      glycans and phosphorylation and dephosphorylation on protein kinase CK2-sensitive
      sites. METHODS: Here, we tested whether the distribution of molecular forms
      changes in heart failure (HF) reflecting possible remodeling of diseased tissue.
      Canine hearts were paced (220 beats/min) for 6-8 weeks to induce heart failure.
      Calsequestrin was purified from heart failure and sham-operated (control) treated
      canine ventricles and analyzed by electrospray mass spectrometry. RESULTS: The
      results showed striking changes in the mass distribution of calsequestrin
      molecules present in tissue from heart failure (five animals) compared with
      control (five animals). In heart failure, calsequestrin contained glycan
      structures that were uncharacteristic of normal junctional sarcoplasmic
      reticulum, consistent with altered metabolism or altered trafficking through
      secretory compartments. Glycoforms containing Man8,9, expected for a phenotype
      less muscle-like, were more than doubled in heart failure hearts, and molecules
      were also phosphorylated to a higher level. CONCLUSIONS: These data reveal in
      tachycardia-induced heart failure a new and potentially important change in the
      mannose content of calsequestrin glycans, perhaps indicative of defective
      junctional SR trafficking and Ca2+ release complex assembly.

PMID- 15249185
TI  - Inhibition of the Na+/H+ exchanger attenuates the deterioration of ventricular
      function during pacing-induced heart failure in rabbits.
AB  - AIMS: Inhibition of the Na+/H+-exchanger (NHE) preserves myocardial morphology
      and function in rat and mouse models of hypertrophy and failure. The mechanism(s)
      involved in such cardioprotective effects remain(s) unclear, but might involve
      blockade of increased protein kinase activity as observed in untreated hearts.
      METHODS AND RESULTS: We investigated the functional, morphological and
      biochemical consequences of NHE-inhibition with BIIB722 in rabbits with pacing
      induced heart failure (HF). In sham rabbits treated with placebo (n = 9) or
      BIIB722 (30 mg/kg/day po, n = 9), LV end-diastolic diameter (LVEDD) and systolic
      fractional shortening (FS, %) remained unchanged. In HF rabbits (n = 9), LVEDD
      increased and FS decreased from 31.5 +/- 1.4 to 8.1 +/- 0.9 (p < 0.05) at 3 weeks
      of LV pacing (400 bpm). Apoptosis, fibrosis and myocyte cross-sectional area as
      well as p38MAPK phosphorylation and iNOS protein expression were significantly
      increased in HF compared to sham rabbits. The activity of the 90 kDa NHE-kinase
      was greater in HF than in sham rabbits. In HF rabbits receiving BIIB722 prior to
      (18.1 +/- 2.2, n = 9) or following 1 week (15.5 +/- 1.6, n = 7) of pacing, FS at
      3 weeks was better preserved than in untreated HF rabbits (p < 0.05). Apoptosis,
      fibrosis, myocyte cross-sectional area, p38MAPK phosphorylation and iNOS protein
      expression were significantly reduced in HF rabbits receiving BIIB722.
      CONCLUSION: NHE-inhibition attenuates the functional, morphological and
      biochemical derangements of pacing-induced HF in rabbits.

PMID- 15249186
TI  - Transmural changes in size, contractile and electrical properties of SHR left
      ventricular myocytes during compensated hypertrophy.
AB  - OBJECTIVE: Some hypertrophic stimuli provoke responses from myocytes that vary
      across the thickness of the left ventricular wall. The Spontaneously Hypertensive
      Rat (SHR) is a well-established genetic model of hypertension and whole heart
      hypertrophy. Details of transmural responses to hypertension in the SHR are few,
      but are needed if the properties of this model are to be fully understood. We
      therefore tested the hypothesis that left ventricular myocytes of the SHR do not
      respond uniformly to their hypertensive environment. METHODS: The volume,
      contraction and action potentials of enzymically isolated sub-epicardial (EPI)
      mid-myocardial (MID) and sub-endocardial (ENDO) myocytes from the left ventricle
      of 20-week-old SHR and normotensive Wistar-Kyoto (WKY) control rats were
      compared. RESULTS: Compared to WKY, as a single population, SHR myocytes
      displayed concentric hypertrophy (larger volumes with smaller length:width)
      increased t-tubule spacing, larger and prolonged cell shortening and
      intracellular calcium ([Ca2+]i) transients and longer action potentials. However,
      these responses differed across the left ventricular wall. MID myocytes showed
      significantly less hypertrophy than EPI and ENDO myocytes. EPI myocytes showed
      the largest (and significant) increases in cell shortening, [Ca2+]i transients
      and action potential duration, whilst MID myocytes showed the smallest (and non
      significant) changes in these parameters. Real time reverse transcription
      polymerase chain reaction analysis on cardiac tissue suggest that increased
      expression of mRNA for fibronectin-1 and protein kinase Cepsilon are involved in
      the hypertrophic response of the whole heart. CONCLUSIONS: Our findings show that
      in the SHR, the effect of hypertension upon the morphology, mechanical activity
      and electrical activity of left ventricular myocytes is dependent upon their
      transmural location. Therefore, in addition to the overall compensating response
      to hypertension, i.e. increased contractility, there are likely to be regionally
      specific alterations in mechano-electric interactions that may influence the
      properties of this important model, e.g. its pre-disposition to arrhythmia whilst
      still in a compensated state.

PMID- 15249187
TI  - Asymmetric septal hypertrophy in heterozygous cMyBP-C null mice.
AB  - OBJECTIVE: Cardiac myosin-binding protein C (cMyBP-C) gene mutations are involved
      in familial hypertrophic cardiomyopathy (FHC). Many of these mutations produce
      truncated proteins, which are unstable in the cardiac tissue of patients,
      suggesting that haploinsufficiency could account for the development of the
      phenotype. However, existing mouse models of cMyBP-C gene mutations have
      represented hypomorphic alleles without evidence of asymmetric septal
      hypertrophy, a key FHC phenotypic feature. In the present study, we generated a
      new model of cMyBP-C null mice and characterized the phenotype in both
      homozygotes and heterozygotes at different ages. METHODS: The mouse model was
      based upon the targeted deletion of exons 1 and 2, which contain the
      transcription initiation site, and the phenotype was determined by molecular,
      functional and morphological analyses. RESULTS: Herein, we demonstrate that
      inactivation of one or two mouse cMyBP-C alleles leads to different cardiac
      disorders at different post-natal time windows. The homozygous cMyBP-C null mice
      do not express the cMyBP-C gene, develop eccentric left ventricular hypertrophy
      with decreased fractional shortening at 3-4 months of age and a markedly impaired
      relaxation after 9 months. This is associated with myocardial disarray and an
      increase of interstitial fibrosis. The heterozygous cMyBP-C null mice present a
      slight but significant decrease of cMyBP-C amount and develop asymmetric septal
      hypertrophy associated with fibrosis at 10-11 months of age. CONCLUSION: These
      data provide evidence that heterozygous cMyBP-C null mice represent the first
      model with a key feature of human FHC that is asymmetric septal hypertrophy.

PMID- 15249188
TI  - Cross-talk between the survival kinases during early reperfusion: its
      contribution to ischemic preconditioning.
AB  - OBJECTIVES: Recruitment of the survival kinase cascades, PI3K-Akt and Raf-MEK1/2
      Erk1/2, at the time of reperfusion, following a lethal ischemic insult, may
      mediate the protection associated with ischemic preconditioning (IPC). The exact
      interplay between these two kinase cascades in mediating this effect is not
      clear. We examine the 'cross-talk' between these kinase cascades in their
      contribution to IPC-induced protection. METHODS AND RESULTS: In isolated perfused
      rat hearts subjected to 35 min of lethal ischemia +/- ischemic preconditioning,
      the phosphorylation states of Akt, Erk1/2, p70S6K were determined after 15 min of
      reperfusion, and infarct size was measured after 120 min of reperfusion. IPC
      induced a threefold increase in Akt, Erk1/2, and p70S6K phosphorylation, at
      reperfusion. We found that inhibiting the PI3K-Akt (using LY294008) at
      reperfusion induced the phosphorylation of Erk1/2-p70S6K, and conversely, that
      inhibiting the MEK1/2-Erk1/2 pathway (using PD 98059) at reperfusion, induced the
      phosphorylation of Akt, suggesting 'cross-talk' between the two kinase pathways.
      However, this effect was not accompanied by a reduction in infarct size (43.1 +/-
      7.2% with LY 294008 and 57.7 +/- 7.0% with PD 98059 vs. 46.3 +/- 5.8% in control;
      P = NS), suggesting that both the kinase cascades may need to be activated to
      mediate IPC-induced protection. IPC reduced the infarct-risk volume ratio to 17.8
      +/- 2.3% from 46.3 +/- 5.8% in control (P < 0.01). Inhibiting p70S6K, a kinase
      situated downstream of both PI3K and Erk1/2, using rapamycin, abolished IPC
      induced protection (46.0 +/- 7.7% with IPC+RAPA vs. 17.8 +/- 2.3% with IPC; P <
      0.01). CONCLUSIONS: We report that, the survival kinase cascades PI3K-Akt and
      MEK1/2-Erk1/2, which are recruited at the time of reperfusion in response to
      ischemic preconditioning, exhibit 'cross-talk' such that inhibiting one cascade
      activates the other and vice versa. Furthermore, at the time of reperfusion,
      these kinase cascades mediate IPC-induced protection, by acting in concert via
      p70S6K.

PMID- 15249189
TI  - Coronary microembolization does not induce acute preconditioning against
      infarction in pigs-the role of adenosine.
AB  - OBJECTIVE: After coronary microembolization (ME) adenosine is released from
      ischemic areas of the microembolized myocardium. This adenosine dilates vessels
      in adjacent nonembolized myocardium and increases coronary blood flow. For
      ischemic preconditioning (IP) to protect the myocardium against infarction, an
      increase in the interstitial adenosine concentration (iADO) prior to the
      subsequent ischemia/reperfusion is necessary. We hypothesized that the adenosine
      release after ME is sufficient to increase iADO and protect the myocardium
      against infarction from subsequent ischemia/reperfusion. We have therefore
      compared myocardial protection by either coronary microembolization or ischemic
      preconditioning prior to ischemia/reperfusion. METHODS: In anesthetized pigs, the
      left anterior descending (LAD) was cannulated and perfused from an extracorporeal
      circuit. In 11 pigs, sustained ischemia was induced by 85% inflow reduction for
      90 min (controls). Two other groups of pigs were subjected either to IP (n = 8;
      10-min ischemia/15-min reperfusion) or coronary ME (n = 9; i.c. microspheres; 42
      microm O; 3000 x ml(-1) x min inflow) prior to sustained ischemia. Coronary
      venous adenosine concentration (vADO) and iADO (microdialysis) were measured.
      Infarct size was determined after 2-h reperfusion by triphenyl tetrazolium
      chloride staining. RESULTS: In pigs subjected to IP, infarct size was reduced to
      2.6 +/- 1.1% (mean +/- S.E.M.) vs. 17.0 +/- 3.2% in controls. iADO was increased
      from 2.4 +/- 1.3 to 13.1 +/- 5.8 micromol x l(-1) during the reperfusion
      following IP. In pigs subjected to ME, at 10 min after ME, coronary blood flow
      (38.6 +/- 3.6 to 53.6 +/- 4.3 ml x min(-1)) and vADO (0.25 +/- 0.04 to 0.48 +/-
      0.07 micromol x l(-1)) were increased. However, iADO (2.0 +/- 0.5 at baseline vs.
      2.3 +/- 0.6 micromol x l(-1) at 10 min after ME) did not increase. Infarct size
      induced by sustained ischemia following ME (22.5 +/- 5.2%) was above that of
      controls for any given subendocardial blood flow. CONCLUSION: ME released
      adenosine into the vasculature and increased coronary blood flow. The failure of
      iADO to increase with ME possibly explains the lack of protection against
      infarction after ME.

PMID- 15249190
TI  - Role of NADPH oxidase-mediated superoxide production in the regulation of E
      selectin expression by endothelial cells subjected to anoxia/reoxygenation.
AB  - OBJECTIVE: Anoxia followed by reoxygenation (A/R) increases endothelial cell
      superoxide (O2-) generation which is implicated in E-selectin overexpression. The
      mechanisms which govern these processes are not fully understood and therefore
      the goal of our study was to determine the functional importance of NADPH oxidase
      in the regulation of E-selectin expression in human umbilical veins endothelial
      cells (HUVECs) submitted to A/R. METHODS: O2- production was estimated using
      lucigenin chemiluminescence and formazan accumulation. NADPH oxidase expression
      in HUVECs was studied by RT-PCR and Western blot and E-selectin by Northern blot
      analysis. NFkappaB activation was assessed by electrophoretic mobility shift
      assay. RESULTS: A/R caused an increased O2- production which was inhibited by the
      superoxide dismutase mimetic M40403 (50 micromol/l), the protein kinase C
      inhibitor chelerythrine (10 micromol/l), the NADPH oxidase inhibitor
      diphenyleneiodonium (DPI, 10 micromol/l) and the NADPH oxidase assembly blocker
      apocynin (600 micromol/l). At the end of the anoxic period, the mRNA expression
      and the protein p47phox was increased as compared to normoxic HUVECs. NFkappaB
      activation of anoxic HUVECs was maximal after 1 h of reoxygenation and returned
      to basal normoxic levels after 2 h of reoxygenation. Apocynin reduced the
      NFkappaB activation at 1 h of reoxygenation. E-selectin mRNA expression was
      increased after 3 h of reoxygenation of anoxic HUVECs and the SOD mimetic M40403
      as well as apocynin prevented this overexpression. CONCLUSIONS: Activated NADPH
      oxidase is a critical enzyme in E-selectin overexpression after A/R of HUVECs.
      Moreover, A/R increased expression of membranous and cytosolic NADPH oxidase
      subunits as well as the protein p47phox. Strategies aimed at preventing
      endothelial NADPH oxidase activation and/or activity may be useful in controlling
      leukocyte adhesion during ischemia/reperfusion.

PMID- 15249191
TI  - Endothelium-dependent hyperpolarization in small gastric arteries.
AB  - OBJECTIVE: In many blood vessels, stimulation of the endothelium with various
      vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin
      pathways, a third mechanism evoking dilatation. It is based on hyperpolarization
      of the vascular smooth muscle cell membrane. In the present study, we
      investigated the existence of endothelium-dependent hyperpolarization in small
      gastric arteries of the rat and explored its underlying mechanism. METHODS:
      Membrane potentials were recorded by conventional microelectrode techniques in
      isolated segments of small gastric arteries, the normalized diameter of which was
      determined from the passive wall tension-internal circumference characteristics
      as measured with a myograph. RESULTS: After blocking NO and prostaglandin
      synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane
      hyperpolarization in endothelium intact but not in endothelium-denuded arteries.
      This membrane potential change was increased by pre-exposure to a low
      concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying
      potassium channels. Moreover, the acetylcholine-induced hyperpolarization was
      unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K
      ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium
      independent hyperpolarization after an initial peak depolarization. CONCLUSIONS:
      We conclude that acetylcholine produces endothelium-dependent hyperpolarization
      in gastric small arteries, which does not rely on activation of smooth muscle
      cell inward rectifying K+ channels or Na/K pumps, and might prove to be another
      important regulator of gastric mucosal blood flow.

PMID- 15249192
TI  - Inhibiting long chain fatty Acyl CoA synthetase increases basal and agonist
      stimulated NO synthesis in endothelium.
AB  - OBJECTIVES: Endothelial nitric oxide synthase (eNOS) activation/deactivation is
      associated with cyclic depalmitoylation/repalmitoylation of specific Cys
      residues. The mechanism of depalmitoylation has been identified recently, but
      repalmitoylation remains undefined. We hypothesized that long chain fatty acyl
      CoA synthetase (LCFACoAS) modulates endothelial nitric oxide synthase
      repalmitoylation by limiting palmitoyl CoA availability. METHODS: Human coronary
      endothelial cells were treated with triacsin-C, an inhibitor of long chain fatty
      acyl CoA synthetase, for 24 h. Media nitrite accumulation, eNOS activity, and
      eNOS palmitoylation were measured. Methacholine-induced NO synthesis or vascular
      relaxation were measured in endothelium-intact rat aortae in the presence and
      absence of triacsin-C. RESULTS: Triacsin-C significantly reduced incorporation of
      [3H] palmitate into immunoreactive endothelial nitric oxide synthase and over a
      concentration range of 0.1 to 10 microM, increased media nitrite accumulations 2-
      to 2.5-fold over baseline. Total in vitro catalytic activity of nitric oxide
      synthase in triacsin-C treated cells did not differ significantly from control.
      Triacsin-C significantly increased methacholine-induced NO synthesis in the
      isolated rat aorta, and significantly enhanced methacholine-induced relaxation of
      rat aortic rings. CONCLUSIONS: These data are consistent with the interpretation
      that inhibition of palmitoylation increases endothelial nitric oxide synthase
      activity without changing endothelial nitric oxide synthase expression,
      suggesting that inhibiting palmitoylation increases the catalytically active
      fraction of endothelial nitric oxide synthase.

PMID- 15249193
TI  - Wild-type but not interferon-gamma-deficient T cells induce graft arterial
      disease in the absence of B cells.
AB  - OBJECTIVE: Interferon-gamma (IFN-gamma), a cytokine produced primarily by T cells
      and by activated macrophages, plays a central role in the pathogenesis of graft
      arterial disease (GAD). This study investigated whether T cells can induce GAD in
      the absence of humoral alloresponses and whether activated macrophages or other
      host cell types can substitute as sources of IFN-gamma in GAD. METHODS: Wild-type
      (WT), IFN-gamma-/-, or recombination-activating-gene-1-/- (RAG-1-/-; lacking
      mature T and B cells) mice received MHC II-disparate hearts. The grafts were
      harvested 8 weeks post-transplant and histological and immunohistochemical
      analyses, RNase protection assay (RPA), and flow cytometry were used to evaluate
      GAD lesions, infiltrating cell populations, and IFN-gamma expression by
      infiltrating cells. RESULTS: Moderate-to-severe GAD developed in WT recipient
      allografts, associated with abundant IFN-gamma expression by both infiltrating T
      cells and macrophages. No GAD developed in IFN-gamma-/- or in RAG-1-/- hosts, nor
      was any IFN-gamma expression evident. RAG-1-/- hosts receiving naive WT or IFN
      gamma-/- T cells (10(7)) after heart transplantation demonstrated no mature B
      cells but showed persistence of transferred T cells up to 8 weeks post
      transplant. In the complete absence of B cells and alloantibody, transfer of WT T
      cells into RAG-1-/- recipients yielded GAD, with associated IFN-gamma expression
      by the transferred T cells and the host macrophages. Transfer of IFN-gamma-/- T
      cells induced neither GAD nor host macrophage IFN-gamma expression. CONCLUSIONS:
      T cells, even in the absence of B cells, suffice to induce GAD, and T cell
      derived IFN-gamma plays a critical role in GAD pathogenesis.

PMID- 15249194
TI  - Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the
      rapid activation of a vagal anti-inflammatory pathway.
AB  - OBJECTIVE: Several melanocortin peptides have a prompt and sustained
      resuscitating effect in conditions of hemorrhagic shock. The transcription
      nuclear factor kappaB (NF-kappaB) triggers a potentially lethal systemic
      inflammatory response, with marked production of tumor necrosis factor-alpha (TNF
      alpha), in hemorrhagic shock. Here we investigated whether the hemorrhagic shock
      reversal produced by the melanocortin ACTH-(1-24) (adrenocorticotropin) depends
      on the activation of the recently recognized, vagus nerve-mediated, brain
      "cholinergic anti-inflammatory pathway". METHODS AND RESULTS: Anesthetized rats
      were stepwise bled until mean arterial pressure (MAP) stabilized at 20-25 mm Hg.
      The severe hypovolemia was incompatible with survival, and all saline-treated
      animals died within 30 min. In rats intravenously (i.v.) treated with ACTH-(1
      24), neural efferent activity along vagus nerve (monitored by means of a standard
      system for extracellular recordings) was markedly increased, and the restoration
      of cardiovascular and respiratory functions was associated with blunted NF-kappaB
      activity and with decreased TNF-alpha mRNA liver content and TNF-alpha plasma
      levels. Bilateral cervical vagotomy, pretreatment with the melanocortin MC(4)
      receptor antagonist HS014, atropine sulfate or chlorisondamine, but not with
      atropine methylbromide, prevented the life-saving effect of ACTH-(1-24) and the
      associated effects on NF-kappaB activity and TNF-alpha levels. HS014 and atropine
      sulfate prevented, too, the ACTH-(1-24)-induced increase in neural efferent vagal
      activity, and accelerated the evolution of shock in saline-treated rats.
      CONCLUSIONS: The present data show, for the first time, that the melanocortin
      ACTH-(1-24) suppresses the NF-kappaB-dependent systemic inflammatory response
      triggered by hemorrhage, and reverses shock condition, by brain activation (in
      real-time) of the "cholinergic anti-inflammatory pathway", this pathway seeming
      to be melanocortin-dependent.

PMID- 15249195
TI  - Calmodulin-binding domains in Alzheimer's disease proteins: extending the calcium
      hypothesis.
AB  - The calcium hypothesis of Alzheimer's disease (AD) invokes the disruption of
      calcium signaling as the underlying cause of neuronal dysfunction and ultimately
      apoptosis. As a primary calcium signal transducer, calmodulin (CaM) responds to
      cytosolic calcium fluxes by binding to and regulating the activity of target CaM
      binding proteins (CaMBPs). Ca(2+)-dependent CaMBPs primarily contain domains
      (CaMBDs) that can be classified into motifs based upon variations on the basic
      amphiphilic alpha-helix domain involving conserved hydrophobic residues at
      positions 1-10, 1-14 or 1-16. In contrast, an IQ or IQ-like domain often mediates
      Ca(2+)-independent CaM-binding. Based on these attributes, a search for CaMBDs
      reveals that many of the proteins intimately linked to AD may be calmodulin
      binding proteins, opening new avenues for research on this devastating disease.

PMID- 15249196
TI  - p44/42(ERK1/2) MAPK and PLD activation by PGD2 preserves papillary
      phosphatidylcholine homeostasis.
AB  - Previous works from our laboratory demonstrated that PGD(2) modulates
      phosphatidylcholine (PC) biosynthesis in renal papillary tissue. In the present
      work, we have evaluated the mechanism by which PGD(2) exerts this action. PGD(2)
      caused two stimulatory waves in PC synthesis which were reproduced by its full
      agonist BW245C. At 1min stimulation, PGD(2) increased PC synthesis by 131%; this
      increase was blocked by neomycin and ethanol, cheleritrine and U0126, PLD, PKC,
      and MEK1/2 inhibitors, respectively. A second PC synthesis increase (100%) was
      observed after 15min, which was blocked by PLD inhibitors. PGD(2) also increased
      phospho-ERK1/2 MAPK in a biphasic-fashion, which was abolished by PLC and PKC
      inhibitors but not by ethanol, which overincreased phospho-ERK1/2, suggesting
      that PGD(2)-induced ERK1/2 activation requires previous PLC-PKC activation while
      PLD down-regulates it. Our results indicate that PGD(2) stimulatory effect
      involves both PLD and ERK1/2-MAPK activation, and both pathways operate
      independently of PC synthesis homeostasis.

PMID- 15249197
TI  - Lbc proto-oncogene product binds to and could be negatively regulated by
      metastasis suppressor nm23-H2.
AB  - Lbc was identified as transforming gene from human leukemic cells and encodes Rho
      type guanine nucleotide exchange factor with 47kDa molecular weight. We isolated
      overlapping cDNAs of Lbc from human lung tissue. Full-length Lbc cDNA encodes
      309kDa huge protein with Ht31 PKA anchoring motif, Dof domain, C1 domain, and
      coiled-coil structure. In order to analyze the regulatory mechanism of its
      activity, we searched for binding proteins. By yeast two-hybrid screening, we
      identified metastasis suppressor nm23-H2 as binding protein, which interacts with
      amino-terminal region of Lbc containing Dof domain. nm23 gene family encodes
      nucleoside diphosphate kinase, however, the binding of nm23-H2 to Lbc was
      independent of kinase activity. nm23-H1, which binds to Rac-specific GEF Tiam1,
      could not bind to Lbc suggesting nm23-H2 would be specific regulator for Lbc.
      Expression of nm23-H2 in cells leads to decrease the amount of GTP-bound Rho and
      suppress stress fiber formation stimulated by expression of Lbc. Our data suggest
      that metastasis suppressor nm23-H2 could regulate Lbc negatively by binding to
      amino-terminal region of Lbc proto-oncogene product.

PMID- 15249198
TI  - p21(Cip-1/SDI-1/WAF-1) expression via the mitogen-activated protein kinase
      signaling pathway in insulin-induced chondrogenic differentiation of ATDC5 cells.
AB  - The embryonal carcinoma-derived cell line, ATDC5, differentiates into
      chondrocytes in response to insulin or insulin-like growth factor-I stimulation.
      In this study, we investigated the roles of mitogen-activated protein (MAP)
      kinases in insulin-induced chondrogenic differentiation of ATDC5 cells. Insulin
      induced accumulation of glycosaminoglycan and expression of chondrogenic
      differentiation markers, type II collagen, type X collagen, and aggrecan mRNA
      were inhibited by the MEK1/2 inhibitor (U0126) and the p38 MAP kinase inhibitor
      (SB203580). Conversely, the JNK inhibitor (SP600125) enhanced the synthesis of
      glycosaminoglycan and expression of chondrogenic differentiation markers. Insulin
      induced phosphorylation of ERK1/2 and JNK but not that of p38 MAP kinase. We have
      previously clarified that the induction of the cyclin-dependent kinase inhibitor,
      p21(Cip-1/SDI-1/WAF-1), is essential for chondrogenic differentiation of ATDC5
      cells. To assess the relationship between the induction of p21 and MAP kinase
      activity, we investigated the effect of these inhibitors on insulin-induced p21
      expression in ATDC5 cells. Insulin-induced accumulation of p21 mRNA and protein
      was inhibited by the addition of U0126 and SB203580. In contrast, SP600125
      enhanced it. Inhibitory effects of U0126 or stimulatory effects of SP600125 on
      insulin-induced chondrogenic differentiation were observed when these inhibitors
      exist in the early phase of differentiation, suggesting that MEK/ERK and JNK act
      on early phase differentiation. SB202580, however, is necessary not only for
      early phase but also for late phase differentiation, indicating that p38 MAP
      kinase stimulates differentiation by acting during the entire period of
      cultivation. These results for the first time demonstrate that up-regulation of
      p21 expression by ERK1/2 and p38 MAP kinase is required for chondrogenesis, and
      that JNK acts as a suppressor of chondrogenesis by down-regulating p21
      expression.

PMID- 15249199
TI  - Role of lateral cell-cell border location and extracellular/transmembrane domains
      in PECAM/CD31 mechanosensation.
AB  - Phosphorylation of tyrosine residues on platelet-endothelial cell adhesion
      molecule-1 (PECAM-1), followed by signal transduction events, has been described
      in endothelial cells following exposure to hyperosmotic and fluid shear stress.
      However, it is unclear whether PECAM-1 functions as a primary mechanosensor in
      this process. Utilizing a PECAM-1-null EC-like cell line, we examined the
      importance of cellular localization and the extracellular and transmembrane
      domains in PECAM-1 phosphorylation responses to mechanical stress. Tyrosine
      phosphorylation of PECAM-1 was stimulated in response to mechanical stress in
      null cells transfected either with full length PECAM-1 or with PECAM-1 mutants
      that do not localize to the lateral cell-cell adhesion site and that do not
      support homophilic binding between PECAM-1 molecules. Furthermore, null cells
      transfected with a construct that contains the intact cytoplasmic domain of PECAM
      1 fused to the extracellular and transmembrane domains of the interleukin-2
      receptor also underwent mechanical stress-induced PECAM-1 tyrosine
      phosphorylation. These findings suggest that mechanosensitive PECAM-1 may lie
      downstream of a primary mechanosensor that activates a tyrosine kinase.

PMID- 15249200
TI  - Inhibitory selectivity of canecystatin: a recombinant cysteine peptidase
      inhibitor from sugarcane.
AB  - The cDNA of a cystein peptidase inhibitor was isolated from sugarcane and
      expressed in Escherichia coli. The protein, named canecystatin, has previously
      been shown to exert antifungal activity on the filamentous fungus Trichoderma
      reesei. Herein, the inhibitory specificity of canecystatin was further
      characterized. It inhibits the cysteine peptidases from plant source papain (Ki
      =3.3nM) and baupain (Ki=2.1x10(-8)M), but no inhibitory effect was observed on
      ficin or bromelain. Canecystatin also inhibits lysosomal cysteine peptidases such
      as human cathepsin B (Ki=125nM), cathepsin K (Ki=0.76nM), cathepsin L (Ki=0.6nM),
      and cathepsin V (Ki=1.0nM), but not the aspartyl peptidase cathepsin D. The
      activity of serine peptidases such as trypsin, chymotrypsin, pancreatic, and
      neutrophil elastases, and human plasma kallikrein is not affected by the
      inhibitor, nor is the activity of the metallopeptidases angiotensin converting
      enzyme and neutral endopeptidase. This is the first report of inhibitory activity
      of a sugarcane cystatin on cysteine peptidases.

PMID- 15249201
TI  - EPO receptor-mediated ERK kinase and NF-kappaB activation in erythropoietin
      promoted differentiation of astrocytes.
AB  - Erythropoietin (EPO), a hematopoietic factor, is also required for normal brain
      development, and its receptor is localized in brain. Therefore, it is possible
      that EPO could act as a neurotropic factor inducing differentiation of neurons.
      In the present study, we investigated whether EPO can promote differentiation of
      neuronal stem cells into astrocytes. In primary culture of cortical neuronal stem
      cells isolated from post neonatal (Day 1) rat brain, EPO dose (0.1-10U/ml)
      dependently promoted initiation of morphological differentiation of astrocyte and
      expression of an astrocyte marker protein, glial fibrillary acidic protein
      (GFAP). Expression of EPO receptor was also increased during morphological
      differentiation of astrocytes. EPO-induced increased morphological
      differentiation of astrocytes and GFAP expression were reduced by treatment with
      anti-EPO and EPO receptor antibodies. Since our previous study showed that
      activation of MAPK family and transcription factors is differentially involved in
      neuronal cell differentiation, we further determined the activation of MAP kinase
      family and NF-kappaB during morphological differentiation of astrocytes.
      Concomitant with the progression of the morphological differentiation of
      astrocytes, ERK(2) but not JNK(1) and p38 MAPK as well as NF-kappaB were
      activated. However, in the presence of PD98,059, an inhibitor of ERK, and
      salicylic acid, an NF-kappaB inhibitor, the EPO-induced morphological
      differentiation of astrocytes and expression of FGAP and EPO receptor were
      reduced. Conversely, treatment with anti-EPO and EPO receptor antibodies also
      reduced EPO-induced ERK(2) and NF-kappaB activation. These data demonstrate that
      EPO can promote differentiation of neuronal stem cells into astrocytes in an EPO
      receptor dependent manner, and this effect may be associated with the activation
      of ERK kinase and NF-kappaB pathway.

PMID- 15249202
TI  - Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular
      invasiveness.
AB  - The Eph tyrosine kinases interact with ligands of the Ephrin family and have
      diverse cellular functions. EphA2 has been recognized to be an oncoprotein of
      importance in a range of cancers. Here, we examine the effect of EphA2
      overexpression and ligation by chimeric Ephrin A1-Fc on the invasive phenotype of
      pancreatic adenocarcinoma cells. We show that EphA2 overexpression induces a FAK
      dependent increase in MMP-2 expression and invasiveness. EphA2 ligation induces
      proteosomal degradation of EphA2, attenuates the invasive phenotype, and
      decreases both FAK phosphorylation and MMP-2 expression. EphA2 appears to
      represent a rational therapeutic target and ligation by Ephrin A1-Fc is one
      strategy to modulate levels of this oncoprotein.

PMID- 15249203
TI  - A study on the immune receptors for polysaccharides from the roots of Astragalus
      membranaceus, a Chinese medicinal herb.
AB  - The immunopotentiating effect of the roots of Astragalus membranaceus, a
      medicinal herb, has been associated with its polysaccharide fractions (Astragalus
      polysaccharides, APS). We herein demonstrate that APS activates mouse B cells and
      macrophages, but not T cells, in terms of proliferation or cytokine production.
      Fluorescence-labeled APS (fl-APS) was able to selectively stain murine B cells,
      macrophages and a also human tumor cell line, THP-1, as determined in flow
      cytometric analysis and confocal laser scanning microscopy. The specific binding
      of APS to B cells and macrophages was competitively inhibited by bacterial
      lipopolysaccharides. Rabbit-anti-mouse immunoglobulin (Ig) antibody was able to
      inhibit APS-induced proliferation of, and APS binding to, mouse B cells.
      Additionally, APS effectively stimulated the proliferation of splenic B cells
      from C3H/HeJ mice that have a mutated TLR4 molecule incapable of signal
      transduction. These results indicate that APS activates B cells via membrane Ig
      in a TLR4-independent manner. Interestingly, macrophages from C3H/HeJ mice were
      unable to respond to APS stimulation, suggesting a positive involvement of the
      TLR4 molecule in APS-mediated macrophage activation. Monoclonal Ab against mouse
      TLR4 partially inhibited APS binding with macrophages, implying direct
      interaction between APS and TLR4 on cell surface. These results may have
      important implications for our understanding on the molecular mechanisms of
      immunopotentiating polysaccharides from medicinal herbs.

PMID- 15249204
TI  - Protein recycling is a major component of post-irradiation recovery in
      Deinococcus radiodurans strain R1.
AB  - Exposure to 6kGy dose of (60)Co gamma-rays resulted in immediate growth arrest,
      followed by complete recovery of Deinococcus radiodurans strain R1 cells.
      Selective degradation and resynthesis of several predicted highly expressed
      proteins (including major chaperones, key TCA cycle enzymes, and few stress
      proteins) and several hypothetical proteins marked the lag period, preceding
      resumption of growth. A major exercise in protein recycling appears to be an
      integral component of post-irradiation recovery in D. radiodurans and complements
      the extensive DNA repair, characteristic of this extremely radioresistant
      bacterium.

PMID- 15249205
TI  - Inhibition of gene expression with double strand RNA interference in Entamoeba
      histolytica.
AB  - In order to inhibit gene expression in Entamoeba histolytica, we have developed a
      method based on expressing double strand RNA interference constructs in stable
      transformants. The 5' end of Eh Dia was cloned head to head with an intervening
      non-specific stuffer fragment in the E. histolytica expression vector pJST4. This
      construct was transformed in E. histolytica HM1:IMSS trophozoites and stable
      transformants were selected with 20microg/ml G418. Our results show that
      expression of Eh Dia was completely inhibited in these transformants. These
      stable transformants could be maintained indefinitely without expression of Eh
      Dia. This method therefore provides an effective tool to study the phenotypic
      changes, which occur due to inhibition of gene expression in the absence of
      mutants and other microbiological manipulations in this protozoan parasite.

PMID- 15249206
TI  - Plasmalemmal V-H(+)-ATPases regulate intracellular pH in human lung microvascular
      endothelial cells.
AB  - The lung endothelium layer is exposed to continuous CO(2) transit which exposes
      the endothelium to a substantial acid load that could be detrimental to cell
      function. The Na(+)/H(+) exchanger and HCO(3)(-)-dependent H(+)-transporting
      mechanisms regulate intracellular pH (pH(cyt)) in most cells. Cells that cope
      with high acid loads might require additional primary energy-dependent
      mechanisms. V-H(+)-ATPases localized at the plasma membranes (pmV-ATPases) have
      emerged as a novel pH regulatory system. We hypothesized that human lung
      microvascular endothelial (HLMVE) cells use pmV-ATPases, in addition to
      Na(+)/H(+) exchanger and HCO(3)(-)-based H(+)-transporting mechanisms, to
      maintain pH(cyt) homeostasis. Immunocytochemical studies revealed V-H(+)-ATPase
      at the plasma membrane, in addition to the predicted distribution in vacuolar
      compartments. Acid-loaded HLMVE cells exhibited proton fluxes in the absence of
      Na(+) and HCO(3)(-) that were similar to those observed in the presence of either
      Na(+), or Na(+) and HCO(3)(-). The Na(+)- and HCO(3)(-)-independent pH(cyt)
      recovery was inhibited by bafilomycin A(1), a V-H(+)-ATPase inhibitor. These
      studies show a Na(+)- and HCO(3)(-)-independent pH(cyt) regulatory mechanism in
      HLMVE cells that is mediated by pmV-ATPases.

PMID- 15249207
TI  - Blockage of RNA polymerase II at a cyclobutane pyrimidine dimer and 6-4
      photoproduct.
AB  - The blockage of transcription elongation by RNA polymerase II (pol II) at a DNA
      damage site on the transcribed strand triggers a transcription-coupled DNA repair
      (TCR), which rapidly removes DNA damage on the transcribed strand of the
      expressed gene and allows the resumption of transcription. To analyze the effect
      of UV-induced DNA damage on transcription elongation, an in vitro transcription
      elongation system using pol II and oligo(dC)-tailed templates containing a
      cyclobutane pyrimidine dimer (CPD) or 6-4 photoproduct (6-4PP) at a specific site
      was employed. The results showed that pol II incorporated nucleotides opposite
      the CPD and 6-4PP and then stalled. Pol II formed a stable ternary complex
      consisting of pol II, the DNA damage template, and the nascent transcript.
      Furthermore, atomic force microscopy imaging revealed that pol II stalled at the
      damaged region. These findings may provide the basis for analysis of the
      initiation step of TCR.

PMID- 15249208
TI  - CpG oligodeoxynucleotides directly induce CXCR3 chemokines in human B cells.
AB  - CpG oligodeoxynucleotides (CpG ODN) are known to elicit Th1 immune responses via
      TLR9. However, the precise mechanisms through which B cells are involved in this
      phenomenon are not fully understood. We investigated the effect of CpG ODN on the
      induction of Th1-chemoattractant CXCR3 chemokines, IP-10, Mig, and I-TAC, in B
      cells. Cells from the RPMI 8226 human B cell line and human peripheral B cells
      were stimulated with three distinct classes of CpG ODN. As a result, CXCR3
      chemokines were strongly up-regulated by CpG-B and CpG-C, but only weakly by CpG
      A. Though CXCR3 chemokines are known to be induced by IFNs, blocking mAbs against
      IFN receptors did not inhibit their induction by CpG-B. Induction of CXCR3
      chemokines was blocked by two NF-kappaB inhibitors and a p38 inhibitor. These
      results strongly suggest that CXCR3 chemokines are directly induced by CpG ODN
      via NF-kappaB- and p38-dependent pathways in human B cells.

PMID- 15249209
TI  - Glypican-1 antisense transfection modulates TGF-beta-dependent signaling in Colo
      357 pancreatic cancer cells.
AB  - The heparan sulfate proteoglycan glypican-1 is essential as a co-receptor for
      heparin binding growth factors, such as HB-EGF and FGF-2, in pancreatic cancer
      cells. In the present study, the role of glypican-1 in the regulation of TGF-beta
      signaling was investigated. Colo-357 pancreatic cancer cells were stably
      transfected with a full-length glypican-1 antisense construct. Cell growth was
      determined by MTT and soft agar assays. TGF-beta1 induced p21 expression and
      Smad2 phosphorylation were analyzed by immunoblotting. PAI-1 promoter activity
      was determined by luciferase assays. Down-regulation of glypican-1 expression by
      stable transfection of a full-length glypican-1 antisense construct resulted in
      decreased anchorage-dependent and -independent cell growth in Colo-357 pancreatic
      cancer cells and attenuated TGF-beta1 induced cell growth inhibition, Smad2
      phosphorylation, and PAI-1 promoter activity. There was, however, no significant
      difference in TGF-beta1 induced p21 expression and Smad2 nuclear translocation.
      In conclusion, glypican-1 is required for efficient TGF-beta1 signaling in
      pancreatic cancer cells.

PMID- 15249210
TI  - 3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3
      dioxygenase pathway, suppresses inducible nitric oxide synthase expression by
      enhancing heme oxygenase-1 expression.
AB  - Inducible nitric oxide (NO) synthase (iNOS), heme oxygenase (HO)-1, and
      indoleamine 2,3-dioxygenase (IDO) are simultaneously expressed in murine
      macrophages stimulated with interferon (IFN)-gamma and lipopolysaccharide (LPS).
      NO produced by iNOS suppresses IDO expression and also induces HO-1 expression.
      The antioxidant 3-hydroxyanthranilic acid (HA), one of metabolites of tryptophan
      via IDO pathway, has been previously reported to suppress iNOS expression.
      Because HO-1 expression can suppress iNOS expression, we investigated whether HA
      could suppress iNOS expression by affecting HO-1 expression in murine RAW 264.7
      macrophages stimulated with IFN-gamma plus LPS. Treatment with exogenous HA dose
      dependently suppressed iNOS expression and coincidently enhanced HO-1 expression.
      This suppressive effect of HA on iNOS expression was reversed by blocking HO-1
      activity, and proven to be due to carbon monoxide (CO) produced by HO-1. In
      addition, either blocking of iNOS activity or addition of exogenous CO further
      enhanced IDO expression and activity. These results show for the first time that
      HA is able to suppress iNOS expression by enhancing HO-1 expression, thereby
      resulting in further increases in IDO expression and activity.

PMID- 15249211
TI  - Shear stress inhibits while disuse promotes osteocyte apoptosis.
AB  - Cell apoptosis operates as an organizing mechanism in biology in addition to
      removing effete cells. We have recently proposed that during bone remodeling,
      osteocyte apoptosis steers osteonal alignment in relation to mechanical loading
      of the whole bone [J. Biomech. 36 (2003) 1453]. Here we present evidence that
      osteocyte apoptosis in cell culture is modulated by shear stress. Under static
      culture conditions, serum starved osteocytes exposed phosphatidylserine (PS) on
      their cell membrane 6x more often than periosteal fibroblasts and 3x more often
      than osteoblasts. Treatment with shear stress reduced the number of osteocytes
      that exposed PS by 90%, but did not affect the other cell types. Fluid shear
      stress of increasing magnitude, dose-dependently stimulated Bcl-2 mRNA expression
      in human bone cells, while shear stress did not change Bax expression. These data
      suggest that disuse promotes osteocyte apoptosis, while mechanical stimulation by
      fluid shear stress promotes osteocyte survival, by modulating the Bcl-2/Bax
      expression ratio.

PMID- 15249212
TI  - Physical conditioning modulates rat cardiac vascular endothelial growth factor
      gene expression in nitric oxide-deficient hypertension.
AB  - Many individuals with cardiac diseases undergo periodic physical conditioning
      with or without medication to improve cardiovascular health. Therefore, this
      study investigated the interaction of physical training and chronic nitric oxide
      synthase (NOS) inhibitor (nitro-L-arginine methyl ester, L-NAME) treatment on
      blood pressure (BP), cardiac vascular endothelial factor (VEGF) gene expression,
      and nitric oxide (NO) systems in rats. Fisher 344 rats were divided into four
      groups and treated as follows: (1) sedentary control, (2) exercise training (ET)
      for 8 weeks, (3) L-NAME (10mg/kg, s.c. for 8 weeks), and (4) ET+L-NAME. BP was
      monitored with tail-cuff method. The animals were sacrificed 24h after last
      treatments and hearts were isolated and analyzed. Physical conditioning
      significantly increased respiratory exchange ratio, cardiac NO levels, NOS
      activity, endothelial eNOS, and inducible iNOS protein expression as well as VEGF
      gene expression. Training also caused depletion of cardiac malondialdehyde (MDA)
      levels indicating the beneficial effects of the training. Chronic L-NAME
      administration resulted in a depletion of cardiac NO level, NOS activity, and
      eNOS, nNOS, and iNOS protein expressions, as well as VEGF gene expression (2-fold
      increase in VEGF mRNA). Chronic L-NAME administration also enhanced cardiac MDA
      levels indicating cardiac oxidative injury. These biochemical changes were
      accompanied by increases in BP after L-NAME administration. Interaction of
      training and NOS inhibitor treatment resulted in normalization of BP and up
      regulation of cardiac VEGF gene expression. The data suggest that physical
      conditioning attenuated the oxidative injury caused by chronic NOS inhibition by
      up-regulating the cardiac VEGF and NO levels and lowering the BP in rats.

PMID- 15249213
TI  - Structure and expression of an unusually acidic matrix protein of pearl oyster
      shells.
AB  - We report identification and characterization of the unusually acidic molluscan
      shell matrix protein Aspein, which may have important roles in calcium carbonate
      biomineralization. The Aspein gene (aspein) encodes a sequence of 413 amino
      acids, including a high proportion of Asp (60.4%), Gly (16.0%), and Ser (13.2%),
      and the predicted isoelectric point is 1.45; this is the most acidic of all the
      molluscan shell matrix proteins sequenced so far, or probably even of all known
      proteins on earth. The main body of Aspein is occupied by (Asp)(2-10) sequences
      punctuated with Ser-Gly dipeptides. RT-PCR demonstrated that the transcript of
      aspein is expressed at the outer edge of the mantle, corresponding to the
      calcitic prismatic layer, but not at the inner part of the mantle, corresponding
      to the aragonitic nacreous layer. Our findings and previous in vitro experiments
      taken together suggest that Aspein is responsible for directed formation of
      calcite in the shell of the pearl oyster Pinctada fucata.

PMID- 15249214
TI  - Inhibition of the functions of the nucleocapsid protein of human immunodeficiency
      virus-1 by an RNA aptamer.
AB  - The nucleocapsid (NC) protein plays many roles in the life cycle of human
      immunodeficiency virus type-1 (HIV-1). Previously we selected the NC binding RNA
      aptamers from diverse forms of RNA libraries. Here we used one of the RNA
      aptamers to the NC protein, N70-13, and tested its effect on NC protein in vitro
      and in cells. The high affinity RNA aptamer completely abolished NC binding to
      the stable transactivation response hairpin and psi RNA stem-loops of HIV-1 RNA.
      When it was expressed in cells as an intramer it inhibited the packaging of viral
      genomic RNA and therefore promises to be an effective anti-HIV therapeutic tool.

PMID- 15249215
TI  - Heat-stable chloroplastic Cu/Zn superoxide dismutase in Chenopodium murale.
AB  - Chenopodium murale is a weed species having wide adaptation to different climatic
      regimes and experiences a temperature range of 5-45 degrees C during its life
      span. Higher temperatures may result in heat stress, which induces higher ROS
      production leading to oxidative stress in the plant. Superoxide dismutase enzyme
      (SOD, EC.1.15.1.1) is ubiquitous, being widely distributed among O(2)(-)
      consuming organisms and is the first line of defense against oxidative stress. In
      this study, we have characterized the thermostability of the SOD isozymes from C.
      murale in vitro. The leaf protein extracts, thylakoidal and stromal fractions
      were subjected to elevated temperatures ranging from 50 degrees C to boiling and
      analyzed for activity and isoform pattern of SOD. Out of six SOD isoforms, SOD V
      showed stability even after boiling the extract for 10min. Under high temperature
      treatment (>60 degrees C) there was an appearance of a new SOD band with higher
      electrophoretic mobility. The inhibitor studies and subcellular analysis revealed
      that the SOD V isoform was a chloroplastic Cu/Zn SOD. The stromal Cu/Zn SOD (SOD
      V) was more stable than the co-migrating thylakoidal isozyme at 80 degrees C and
      boiling for 10min. Hence, we report an unusual, constitutive thermostable
      chloroplastic Cu/Zn SOD from C. murale, which may contribute towards its heat
      tolerance.

PMID- 15249216
TI  - Implication of the differential roles of metallothionein 1 and 2 isoforms in the
      liver of rats as determined by polyacrylamide-coated capillary zone
      electrophoresis.
AB  - Metallothioneins (MTs), determined by polyacrylamide-coated capillary zone
      electrophoresis (CZE), coincided well with those described by enzyme-linked
      immunosorbent assay. By using CZE, MT isoforms 1 (MT-1) and 2 (MT-2) were well
      separated and determined in the liver cytosol of LEC rats and Wistar rats
      administered CdCl(2). The total concentrations of MTs in the liver cytosol of LEC
      rats increased age-dependently as 1.0, 2.1, and 7.2mg/g wet weight of the liver
      at the age of 5, 10, and 15 weeks, respectively, and those of Wistar rats that
      had received daily CdCl(2) also increased with time of CdCl(2) as 0.5 and 1.2mg/g
      wet weight of the liver for 3 and 6 consecutive administration days,
      respectively. The MT-1/MT-2 ratio in the liver cytosol of LEC rats decreased age
      dependently as 1.75, 1.49, and 0.76 at the age of 5, 10, and 15 weeks,
      respectively. In contrast, that of Wistar rats increased with time of exposure to
      the metal ion CdCl(2) as 1.1 and 1.6 for 3 and 6 administration days,
      respectively. Copper accumulation in the liver of LEC rats has already been
      reported. The present results indicated that the mechanism of the induction of MT
      synthesis differs between LEC rats, who lack ATP7B, and Wistar rats, who were
      given a toxic metal ion. On the basis of these results, we propose that MT-1 is
      related to the metabolism or detoxification of toxic metals such as Cd, and in
      contrast, MT-2 is responsible for the homeostasis of essential metals such as Cu.

PMID- 15249217
TI  - Potent and selective inhibition of SARS coronavirus replication by
      aurintricarboxylic acid.
AB  - The severe acute respiratory syndrome virus (SARS) is a coronavirus that
      instigated regional epidemics in Canada and several Asian countries in 2003. The
      newly identified SARS coronavirus (SARS-CoV) can be transmitted among humans and
      cause severe or even fatal illnesses. As preventive vaccine development takes
      years to complete and adverse reactions have been reported to some veterinary
      coronaviral vaccines, anti-viral compounds must be relentlessly pursued. In this
      study, we analyzed the effect of aurintricarboxylic acid (ATA) on SARS-CoV
      replication in cell culture, and found that ATA could drastically inhibit SARS
      CoV replication, with viral production being 1000-fold less than that in the
      untreated control. Importantly, when compared with IFNs alpha and beta, viral
      production was inhibited by more than 1000-fold as compared with the untreated
      control. In addition, when compared with IFNs alpha and beta, ATA was
      approximately 10 times more potent than IFN alpha and 100 times more than
      interferon beta at their highest concentrations reported in the literature
      previously. Our data indicated that ATA should be considered as a candidate anti
      SARS compound for future clinical evaluation.

PMID- 15249218
TI  - Mechanisms of cholesterol and sterol regulatory element binding protein
      regulation of the sterol 12alpha-hydroxylase gene (CYP8B1).
AB  - Sterol 12alpha-hydroxylase (CYP8B1) is an obligatory enzyme for the synthesis of
      cholic acid and regulation of liver bile acid synthesis and intestine cholesterol
      absorption. The present study evaluates the roles for sterol regulatory element
      binding proteins (SREBPs) in the regulation of the CYP8B1 gene. Cholesterol
      feeding of mice and rats decreased the activity of CYP8B1, contrary to the up
      regulation of cholesterol 7alpha-hydroxylase (CYP7A1). Cholesterol feeding also
      reduced mRNA levels for SREBP-1 but not for SREBP-2 in rat livers. Cholesterol
      and 25-hydroxycholesterol decreased the CYP8B1/luciferase reporter activity. Co
      transfection of SREBP-1a and -1c stimulated CYP8B1 promoter activity, while SREBP
      2 did not have any effects. Electrophoretic mobility shift assay and mutagenesis
      analyses identified several functional sterol regulatory elements (SRE) and E-box
      motifs in the rat CYP8B1 promoter. Our results indicate that SREBP-1a and -1c
      enhance transcription of the CYP8B1 gene through binding to SRE. Cholesterol
      loading reduces SREBP-1 mRNA expression in addition to reducing functional SREBP
      1 protein, and results in decreasing CYP8B1 gene transcription.

PMID- 15249219
TI  - Mutagenesis study on amino acids around the molybdenum centre of the periplasmic
      nitrate reductase from Ralstonia eutropha.
AB  - Molybdenum enzymes containing the pterin cofactor are a diverse group of enzymes
      that catalyse in general oxygen atom transfer reactions. Aiming at studying the
      amino acid residues, which are important for the enzymatic specificity, we used
      nitrate reductase from Ralstonia eutropha (R.e.NAP) as a model system for
      mutational studies at the active site. We mutated amino acids at the Mo active
      site (Cys181 and Arg421) as well as amino acids in the funnel leading to it
      (Met182, Asp196, Glu197, and the double mutant Glu197-Asp196). The mutations were
      made on the basis of the structural comparison of nitrate reductases with formate
      dehydrogenases (FDH), which show very similar three-dimensional structures, but
      clear differences in amino acids surrounding the active site. For mutations
      Arg421Lys and Glu197Ala we found a reduced nitrate activity while the other
      mutations resulted in complete loss of activity. In spite of the partial of total
      loss of nitrate reductase activity, these mutants do not, however, display FDH
      activity.

PMID- 15249220
TI  - Thermodynamics of i-tetraplex formation in the nuclease hypersensitive element of
      human c-myc promoter.
AB  - More than 85% of c-myc transcription is controlled by the nuclease hypersensitive
      element III(1) upstream of the P1 promoter of this oncogene. The purine-rich
      sequence in the anti-sense strand forms a G-quadruplex, which has been recently
      implicated in colorectal cancer, and is proposed as a silencer element [Proc.
      Natl. Acad. Sci. USA 101 (2004) 6140]. This prompted us to characterize the
      thermodynamics and proton/counterion effect of the complementary pyrimidine-rich
      sequence, which forms a C-tetraplex. We report the thermodynamic parameters for
      folding of the pyrimidine-rich DNA fragment from this region into a C-tetraplex.
      At 20 degrees C, we observed a DeltaG of -10.36+/-0.13kcalmol(-1) with favorable
      enthalpy (DeltaH=75.99+/-0.99kcalmol(-1)) and unfavorable entropy
      (TDeltaS=65.63+/-0.88 kcalmol(-1)) at pH 5.3 in 20mM NaCl for tetraplex folding.
      Similar characteristic stabilizing enthalpy and destabilizing entropy were
      observed at other pH and ionic strengths. Folding was induced by uptake of about
      two to three protons per mole of tetraplex while a marginal (0.5-1mol/mol)
      counterion uptake was observed. In the context of current understanding of c-myc
      transcription we envisage a role of the i-motif in remodeling the G-quadruplex
      silencer.

PMID- 15249221
TI  - Identification of a novel transcript of human PECAM-1 and its role in the
      transendothelial migration of monocytes and Ca2+ mobilization.
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is an integral component
      of endothelial cells and has been implicated in the transendothelial migration
      (TEM) of circulating leukocytes mediated by its 1st and 2nd extracellular
      immunoglobulin (Ig)-like domains and regulation of intracellular Ca(2+)
      homeostasis with its 6th domain. Up-to-date, little is known about the role of
      the 5th extracellular (Ig)-like domain. We have discovered a novel human PECAM-1
      transcript missing the entire 7th exon, which encodes the 5th extracellular (Ig)
      like domain of PECAM-1. A synthetic peptide with sequence homology to the 5th
      domain of PECAM-1 (JHS-7 peptide) and a corresponding polyclonal antibody (JHS-7
      Ab) were prepared and their potential role in transendothelial migration and
      Ca(2+) influx was measured. The JHS-7 peptide and the antibody exerted a dose
      dependent decrease (50-80%) in the transendothelial migration of freshly isolated
      human monocytes and a promonocytic cell line (U-937) in resting HUVECs and HUVECs
      activated with tumor necrosis factor-alpha. This was accompanied by an increase
      in Ca(2+) influx and decrease in refilling of the intracellular Ca(2+) stores in
      HUVECs. In summary, we have identified a novel PECAM-1 transcript (Deltaexon 7)
      and shown that the 5th (Ig)-like domain of PECAM-1 plays a role in monocyte TEM
      and Ca(2+) homeostasis.

PMID- 15249222
TI  - Prediction of protein subcellular locations by GO-FunD-PseAA predictor.
AB  - The localization of a protein in a cell is closely correlated with its biological
      function. With the explosion of protein sequences entering into DataBanks, it is
      highly desired to develop an automated method that can fast identify their
      subcellular location. This will expedite the annotation process, providing timely
      useful information for both basic research and industrial application. In view of
      this, a powerful predictor has been developed by hybridizing the gene ontology
      approach [Nat. Genet. 25 (2000) 25], functional domain composition approach [J.
      Biol. Chem. 277 (2002) 45765], and the pseudo-amino acid composition approach
      [Proteins Struct. Funct. Genet. 43 (2001) 246; Erratum: ibid. 44 (2001) 60]. As a
      showcase, the recently constructed dataset [Bioinformatics 19 (2003) 1656] was
      used for demonstration. The dataset contains 7589 proteins classified into 12
      subcellular locations: chloroplast, cytoplasmic, cytoskeleton, endoplasmic
      reticulum, extracellular, Golgi apparatus, lysosomal, mitochondrial, nuclear,
      peroxisomal, plasma membrane, and vacuolar. The overall success rate of
      prediction obtained by the jackknife cross-validation was 92%. This is so far the
      highest success rate performed on this dataset by following an objective and
      rigorous cross-validation procedure.

PMID- 15249223
TI  - Effect of metal ions on de novo aggregation of full-length prion protein.
AB  - It is well established that the prion protein (PrP) contains metal ion binding
      sites with specificity for copper. Changes in copper levels have been suggested
      to influence incubation time in experimental prion disease. Therefore, we studied
      the effect of heavy metal ions (Cu(2+), Mn(2+), Ni(2+), Co(2+), and Zn(2+)) in
      vitro in a model system that utilizes changes in the concentration of SDS to
      induce structural conversion and aggregation of recombinant PrP. To quantify and
      characterize PrP aggregates, we used fluorescently labelled PrP and cross
      correlation analysis as well as scanning for intensely fluorescent targets in a
      confocal single molecule detection system. We found a specific strong pro
      aggregatory effect of Mn(2+) at low micromolar concentrations that could be
      blocked by nanomolar concentration of Cu(2+). These findings suggest that metal
      ions such as copper and manganese may also affect PrP conversion in vivo.

PMID- 15249224
TI  - Basic fibroblast growth factor antagonizes activin A-mediated growth inhibition
      and hemoglobin synthesis in K562 cells by activating ERK1/2 and deactivating p38
      MAP kinase.
AB  - Activin A can induce erythroid differentiation, whereas basic fibroblast growth
      factor (bFGF) can maintain the undifferentiated status of erythroid progenitors.
      How these two factors together can affect the regulation of erythroid
      differentiation in hematopoietic cells has not been elucidated. This study
      demonstrates that bFGF antagonizes activin A-mediated growth inhibition and
      hemoglobin (Hb) synthesis in K562 cells. Analyses of mitogen-activated protein
      kinases revealed that activin A-induced p38 phosphorylation and inhibited ERK1/2
      phosphorylation. In contrast, bFGF worked antagonistically to induce ERK1/2
      phosphorylation and inhibited p38 phosphorylation in K562 cells. Furthermore, co
      treatment of cells with activin A and bFGF decreased p38 phosphorylation and
      increased ERK1/2 phosphorylation. SB203580 inhibition of p38 activity eliminated
      activin A-mediated growth inhibition and Hb synthesis, whereas U0126 inhibition
      of ERK1/2 activity augmented the effects of activin A on K562 cells. These
      results suggest that bFGF can negatively modulate p38 and positively modulate
      ERK1/2 to antagonize activin A-mediated growth inhibition and Hb synthesis in
      K562 cells.

PMID- 15249225
TI  - Dose-dependence, sex- and tissue-specificity, and persistence of radiation
      induced genomic DNA methylation changes.
AB  - Radiation is a well-known genotoxic agent and human carcinogen that gives rise to
      a variety of long-term effects. Its detrimental influence on cellular function is
      actively studied nowadays. One of the most analyzed, yet least understood long
      term effects of ionizing radiation is transgenerational genomic instability. The
      inheritance of genomic instability suggests the possible involvement of
      epigenetic mechanisms, such as changes of the methylation of cytosine residues
      located within CpG dinucleotides. In the current study we evaluated the dose
      dependence of the radiation-induced global genome DNA methylation changes. We
      also analyzed the effects of acute and chronic high dose (5Gy) exposure on DNA
      methylation in liver, spleen, and lung tissues of male and female mice and
      evaluated the possible persistence of the radiation-induced DNA methylation
      changes. Here we report that radiation-induced DNA methylation changes were sex-
      and tissue-specific, dose-dependent, and persistent. In parallel we have studied
      the levels of DNA damage in the exposed tissues. Based on the correlation between
      the levels of DNA methylation and DNA damage we propose that radiation-induced
      global genome DNA hypomethylation is DNA repair-related.

PMID- 15249226
TI  - D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate, a mimic of d-myo-inositol
      1,3,4,5-tetrakisphosphate: biological activity and pH-dependent conformational
      properties.
AB  - D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate [D-6-deoxy-Ins(1,3,4,5)P(4)] 3
      is a novel deoxygenated analogue of D-myo-inositol 1,3,4,5-tetrakisphosphate
      [Ins(1,3,4,5)P(4)] 2, a central and enigmatic molecule in the
      polyphosphoinositide pathway of cellular signalling. D-6-Deoxy-Ins(1,3,4,5)P(4)
      is a moderate inhibitor of Ins(1,4,5)P(3) 5-phosphatase [1.8microM] compared to
      Ins(1,3,4,5)P(4) [0.15microM] and similar to that of L-Ins(1,3,4,5)P(4)
      [1.8microM]. In displacement of [(3)H] Ins(1,4,5)P(3) from the rat cerebellar
      Ins(1,4,5)P(3) receptor, while slightly weaker [IC(50)=800nM] than that of D
      Ins(1,3,4,5)P(4) [IC(50)=220nM], 3 is less markedly different and again similar
      to that of L-Ins(1,3,4,5)P(4) [IC(50)=660nM]. 3 is an activator of I(CRAC) when
      inward currents are measured in RBL-2H3-M1 cells using patch-clamp
      electrophysiological techniques with a facilitation curve different to that of
      Ins(1,3,4,5)P(4). Physicochemical properties were studied by potentiometric (31)P
      and (1)H NMR titrations and were similar to those of Ins(1,3,4,5)P(4) apart from
      the observation of a biphasic titration curve for the P1 phosphate group. A novel
      vicinal phosphate charge-induced conformational change of the inositol ring above
      pH 10 was observed for D-6-deoxy-Ins(1,3,4,5)P(4) that would normally be hindered
      because of the central stabilising role played by the 6-OH group in
      Ins(1,3,4,5)P(4). We conclude that the 6-OH group in Ins(1,3,4,5)P(4) is crucial
      for its physicochemical behaviour and biological properties of this key inositol
      phosphate.

PMID- 15249227
TI  - Oligomeric Aip2p/Dld2p forms a novel grapple-like structure and has an ATP
      dependent F-actin conformation modifying activity in vitro.
AB  - In order to investigate the molecular mechanism of the F-actin conformation
      modifying activity [Biochem. Biophys. Res. Commun. 319 (2004) 78] of actin
      interacting protein 2 (Aip2p) [Nat. Struct. Biol. 2 (1995) 28]/D-lactate
      dehydrogenase protein 2 (Dld2p) [Yeast 15 (1999) 1377; Biochem. Biophys. Res.
      Commun. 295 (2002) 910], the ultrastructure and the regulatory mechanism of the
      activity were further examined. Interestingly, a novel oligomeric grapple-like
      structure of 10-12 subunits with an ATP-dependent opening was observed. ATP
      regulates the opening and closing of the "gate" that forms the opening within
      oligomeric Aip2p/Dld2p, where binding to the substrate occurs while in the open
      form. In the presence of ATP (open state of oligomeric Aip2p/Dld2p), oligomeric
      Aip2p/Dld2p bound the F-actin fiber within the opening, whereas in the absence of
      ATP (closed state of oligomeric Aip2p/Dld2p), no binding was observed.
      Simultaneously, the oligomeric Aip2p/Dld2p increased the trypsin susceptibility
      of F-actin in an ATP-dependent manner. Use of the non-hydrolyzable ATP analogue
      AMP-PNP yielded similar results to those observed with ATP, suggesting that ATP
      binding rather than ATP hydrolysis is required for the protein conformation
      modifying reaction of oligomeric Aip2p/Dld2p. Endogenous Aip2p/Dld2p purified
      from Saccharomyces cerevisiae also exhibited such protein conformation modifying
      activity, but monomeric Aip2p/Dld2p with a C-terminal coiled-coil region
      truncation failed to exhibit the activity. These data suggest that the
      oligomerization of Aip2p/Dld2p, which exhibits the unique grapple-like structure
      with an ATP-dependent opening, is required for the F-actin conformation modifying
      activity.

PMID- 15249228
TI  - Characterization of mouse endoplasmic reticulum methionine-R-sulfoxide reductase.
AB  - Methionine-R-sulfoxide reductases (MsrBs) catalyze a stereospecific reduction of
      methionine-R-sulfoxides to methionines in proteins. Mammals possess three MsrB
      genes. MsrB1 (SelR) is a selenoprotein located in the cytosol and nucleus, MsrB2
      (CBS-1) is a mitochondrial protein, and MsrB3 is a recently identified protein
      with an unusual localization pattern. Human MsrB3 occurs in two protein forms,
      MsrB3A and MsrB3B, which can be targeted to the endoplasmic reticulum (ER) and
      mitochondria, respectively. These forms are generated by alternative first exon
      splicing that introduces contrasting N-terminal signal peptides. Herein, we
      characterized mouse MsrB3 and found no evidence of alternative splicing of its
      gene. The ER signal was located upstream of the predicted mitochondrial signal
      sequence in a single coding region, whose product was targeted to the ER.
      Although the mitochondrial signal could function if placed at the N-terminus, it
      did not target MsrB3 to mitochondria as part of the entire coding region. In
      addition, immunoblot assays detected no mitochondrial MsrB3 in examined mouse
      tissues. The data suggest that, in mice, MsrB3 is largely or exclusively an ER
      resident protein, and that the reduction of methionine-R-sulfoxides in different
      cellular compartments is provided by individual MsrB isozymes.

PMID- 15249229
TI  - Catalytic residues of group VIB calcium-independent phospholipase A2
      (iPLA2gamma).
AB  - Although human group VIB calcium-independent phospholipase A(2) (iPLA(2)gamma)
      contains the lipase-consensus sequence Gly-Xaa-Ser-Xaa-Gly in the C-terminal
      half, its overall sequence exhibits a week similarity to those of other PLA(2)s,
      and thus no information on the catalytic site has been available. Here we show
      that the C-terminal region of human iPLA(2)gamma is responsible for the enzymatic
      activity. Comparison of this catalytic domain with those of the mouse homologue,
      human cytosolic PLA(2) (cPLA(2)), and the plant PLA(2) patatin reveals that an
      amino acid sequence of a short segment around Asp-627 of iPLA(2)gamma is
      conserved among these PLA(2)s, in addition to the Ser-483-containing lipase
      motif; the corresponding serine and aspartate in cPLA(2) and patatin are known to
      form a catalytic dyad. Since substitution of alanine for either Ser-483 or Asp
      627 results in a loss of the PLA(2) activity, we propose that Ser-483 and Asp-627
      of human iPLA(2)gamma constitute an active site similar to the Ser-Asp dyad in
      cPLA(2) and patatin.

PMID- 15249230
TI  - Expression of a novel cardiac-specific tropomyosin isoform in humans.
AB  - Tropomyosins are a family of actin binding proteins encoded by a group of highly
      conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3,
      and TPM4, each of which is known to generate multiple isoforms by alternative
      splicing, promoters, and 3' end processing. TPM1 is the most versatile and
      encodes a variety of tissue specific isoforms. The TPM1 isoform specific to
      striated muscle, designated TPM1alpha, consists of 10 exons: 1a, 2b, 3, 4, 5, 6b,
      7, 8, and 9a/b. In this study, using RT-PCR with adult and fetal human RNAs, we
      present evidence for the expression of a novel isoform of the TPM1 gene that is
      specifically expressed in cardiac tissues. The new isoform is designated
      TPM1kappa and contains exon 2a instead of 2b. Ectopic expression of human
      GFP.TPM1kappa fusion protein can promote myofibrillogenesis in cardiac mutant
      axolotl hearts that are lacking in tropomyosin.

PMID- 15249231
TI  - Inhibition of transcriptional activities of AP-1 and c-Jun by a new zinc finger
      protein ZNF394.
AB  - Zinc finger proteins play important roles in a variety of cellular functions,
      including cell growth, proliferation, apoptosis, and intracellular signal
      transduction, and the zinc finger-containing transcription factor has been
      implicated as a critical regulator of multiple cardiac-expressed genes as well as
      a regulator of inducible gene expression in response to hypertrophic stimulation.
      With the aim of identifying the genes involved in human heart development and
      diseases, we have isolated a novel LER-related zinc finger gene named ZNF394 from
      human heart cDNA library. ZNF394 gene has a predicted 561-amino acid open reading
      frame, encoding a 64kDa zinc finger protein. The N-terminus of ZNF394 protein has
      a leucine-rich region (LER or SCAN domain), followed by a well-conserved kruppel
      associated box domain. The C-terminus of the protein contains 7 C2H2 zinc finger
      motifs in tandem arrays with the highly conserved space region of the H/C-link.
      ZNF394 gene is mapped to chromosome 7q11.21. Northern blot analysis indicates
      that a 2.18kb transcript specific for ZNF394 is specifically expressed in the
      heart, skeletal muscle, and brain in human adult tissues. ZNF394 protein is
      expressed in cell nucleus. Overexpression of ZNF394 in the cell inhibits the
      transcriptional activities of c-Jun and AP-1 reporters, suggesting that ZNF394 is
      a new transcriptional repressor in mitogen-activated protein kinase signaling
      pathways and may play an important role in cardiac development and/or cardiac
      function.

PMID- 15249232
TI  - Developmental contribution of c-maf in the kidney: distribution and developmental
      study of c-maf mRNA in normal mice kidney and histological study of c-maf
      knockout mice kidney and liver.
AB  - Maf is a family of oncogenes which encodes a nuclear bZip transcription factor
      protein and has been originally identified from the avian oncogenic retrovirus,
      AS42. Maf genes have been reported to have critical roles in embryological
      development and cellular differentiation. In this study, in situ hybridization
      with (35)S-labeled antisense riboprobes was used to investigate the distribution
      of c-maf mRNA in balb/c mouse kidneys from 12 (E12) through 17 days (E17) of
      gestation and then 1 and 4 weeks after birth. Immunocytochemistry of 4-week-old
      mouse kidney using anti-c-maf antisera was also performed. Kidney and liver
      sections from c-maf knockout mice at 4 weeks were stained with hematoxylin-eosin,
      and their histological features were examined. Expression of c-maf mRNA was first
      detected on E16 in the renal proximal tubules, and it was expressed through 4
      weeks after birth. In the c-maf knockout mice at 4 weeks the cytoplasmic volume
      of the proximal tubule and liver cell was smaller. These findings suggest that
      expression of the c-maf gene may be involved in the embryological development
      and/or cell differentiation of kidney and liver cells.

PMID- 15249233
TI  - Procedure incidence and in-hospital complication rates of bariatric surgery in
      the United States.
AB  - BACKGROUND: Complication rates for bariatric surgery have been reported primarily
      from academic centers with specialized programs. The rates may not reflect those
      occurring in the community. METHODS: The National Hospital Discharge Survey
      (NHDS) database maintained by the Center for Disease Control (CDC) was queried to
      determine the national incidence and complication rate for bariatric surgery as
      performed in the United States. RESULTS: The number of bariatric procedures
      rapidly increased from 6,868 in 1996 to 45,473 in 2001, with most of the increase
      attributable to a very large rise in the annual number of Roux-en-Y gastric
      bypasses performed. The in-hospital complication rate was 9.6% and 8.6% of
      patients has a length of stay exceeding 7 days. Cholecystectomies were performed
      concurrently in 28% of cases and were not associated with increases in
      complication rates or longer hospital stays. For those undergoing surgery, the
      most common preoperative comorbid conditions were hypertension (34%), arthritis
      (27%), GERD (22%), sleep apnea (22%), and diabetes (18%). CONCLUSIONS: The rate
      at which bariatric procedures are being performed is rapidly increasing,
      resulting in the need to establish practice standards. In-house complication
      rates derived from a cross section of US practices compare favorably with those
      reported from specialized centers. Based on these nationally representative data,
      the expected in-house clinically significant complication rate for bariatric
      operations is approximately 10%. As that is the average complication rate
      observed nationally, it serves as the benchmark to which bariatric surgery
      programs can compare themselves.

PMID- 15249234
TI  - A nine-year institutional experience with near-total laryngectomy.
AB  - BACKGROUND: Pearson's near-total laryngectomy (NTL) is an alternative procedure
      to total laryngectomy in selected patients with advanced laryngeal cancer. Based
      on our experience with NTL for >9 years, we present here the functional results,
      complications, and survival rates. METHODS: A retrospective study was carried out
      from January 1993 to May 2002. We studied 15 patients with advanced laryngeal,
      oropharyngeal, and hypopharyngeal cancer who underwent NTL. Survival rates were
      calculated using the Kaplan-Meier method. RESULTS: The most common complication
      was fistula (8 of 15) followed by minor aspiration (4 of 15 patients). Eleven
      patients (73.5%) attained a good voice; 3 patients (19.9%) obtained a bad voice;
      and 1 did not achieved vocal ability. Three patients (19.9%) had local
      recurrence; no patients had neck recurrence; and 2 patients (13.3%) had distant
      metastasis. Six patients (40%) died from their disease, and 2 (13.3%) patients
      died from other causes. The 3-year actuarial survival rate was 81.6%.
      CONCLUSIONS: NTL is useful in the treatment of selected patients with advanced
      laryngeal, oropharyngeal, and hypopharyngeal cancer and results in good control
      and survival rates. Satisfactory functional results can be attained in the
      majority of patients. When the surgical margins are positive or close, TL must be
      carried out.

PMID- 15249235
TI  - Cluster of acute hemorrhagic appendicitis among high school students in Wuhan,
      China.
AB  - BACKGROUND: Features of a cluster of acute appendicitis that occurred among a
      high school student population in China were investigated. METHODS: Epidemiologic
      data, medical records, and histologic slides of resected appendices were
      examined. RESULTS: During a period between April 10, 1997, and June 11, 1997, 11
      cases occurred in a high school, with 10 cases among 290 students enrolled at the
      time. From the end of the initial cluster until June, 2000, 20 additional cases
      were encountered. Female cases (6.5%) are more frequent than male cases (1.9%).
      There was a clustering pattern. Many patients had a history of mutual contact
      before the onset of symptoms. Pathologically, the resected appendices exhibited
      diffuse or focal hemorrhages in the lamina propria or within hyperplastic
      lymphoid follicles, and infiltration by eosinophils and by lymphocytes.
      Appendical tissues were examined using immunohistochemistry, but no etiologic
      agent was identified. CONCLUSIONS: This cluster of acute appendicitis represented
      a special kind of appendicitis, with features of an infectious disease in
      epidemiology.

PMID- 15249236
TI  - Breast-conserving therapy and sentinel lymph node biopsy are feasible in cancer
      patients with previous implant breast augmentation.
AB  - BACKGROUND: Breast-conserving therapy (BCT) is reported to result in a
      significant rate of complications and local recurrences in patients with prior
      implant breast augmentation. The role of sentinel lymph node (SLN) biopsy in
      these patients is unknown. METHODS: Retrospective review of patients with prior
      breast augmentation treated with BCT or SLN biopsy. RESULTS: Nineteen breast
      cancers were treated with BCT. Of 17 breasts undergoing adjuvant radiotherapy, 11
      (64.7%) retained favorable aesthetic results. Of 9 subpectoral implants, capsular
      contracture developed in only 1 (11.1%). During follow-up (median 3 years), 1
      local recurrence (5.3%) occurred in a patient who refused adjuvant radiotherapy
      and systemic therapy. Eleven patients underwent SLN biopsy with an identification
      rate of 100% and a false-negative rate of 0%. CONCLUSIONS: Breast-conserving
      therapy inclusive of radiotherapy after implant breast augmentation produced
      acceptable cosmetic results in nearly two-thirds of patients. Sentinel lymph node
      mapping in the setting of prior implant augmentation was highly successful and
      accurate.

PMID- 15249237
TI  - The responsibilities and contributions of professional educators in surgery
      departments.
AB  - BACKGROUND: The purpose of the study is to describe the academic preparation,
      scope of duties, and scholarly activity of professional educators in surgery
      departments. METHODS: Educators with doctoral degrees employed as full-time
      faculty in surgery departments were surveyed to determine terms of employment,
      academic preparation, scope of duties, and job satisfaction. RESULTS: Twelve of
      13 educators responded and participated in the study. Educators spent, on
      average, 22% of their time on research activities, 33% on administrative
      responsibilities, 13% on teaching, 13% counseling students and residents, and 7%
      writing grants. They spent approximately 34% of their time with surgical faculty,
      19% with residents/fellows, and 14% with medical students. Educators'
      contributions to surgery departments included improvements in assessment and
      evaluation, educational conferences, recruitment, and research productivity.
      CONCLUSIONS: Professional educators provide support needed to meet the growing
      demands and requirements of surgical education. Study findings may inform those
      interested in recruiting a professional educator to their faculty.

PMID- 15249238
TI  - Attitudes of applicants for surgical residency toward work hour limitations.
AB  - BACKGROUND: There is an ongoing debate regarding the merits of resident work-hour
      limitations. We postulated that this issue would be a factor in the decision
      making process of applicants to surgical residency. METHODS: Candidates for
      surgical residency at a university-based program completed an anonymous survey
      during their visit. Data was analyzed by analysis of variance and the chi-square
      test. RESULTS: Most candidates viewed work-hour limitations as being favorable to
      their future training. Nevertheless, work-hour limitations ultimately were not a
      critical factor in the decision-making process compared with issues such as
      quality of training and program reputation. Candidates ranked "reading in
      surgery" the most likely way they would spend the leisure time afforded by work
      hour limitations. CONCLUSIONS: Most applicants for surgical residency consider
      work hour-limitations as being favorable to their training and view the extra
      free time as an opportunity for furthering their education. However, other issues
      take precedence when choosing a residency.

PMID- 15249239
TI  - Hormone replacement therapy in postmenopausal women.
AB  - BACKGROUND: For many years, hormone replacement therapy (HRT) was considered an
      effective method of restoring the relative protection from coronary artery
      disease enjoyed by premenopausal women compared with men of similar age. This
      view has been supported by a substantial number of basic science and
      observational studies. DATA SOURCES: Results of recent randomized controlled
      trials have seriously challenged the concept of the protective value of HRT by
      showing that rather than decreasing the risk of coronary artery disease, HRT
      actually appears to increase it. In addition, it increases the risk for breast
      cancer, stroke, venous thromboembolism, and cholecystitis. RESULTS: Despite some
      benefits such as increased bone mineral density and decreased risk of fracture
      and colorectal cancer, these data suggest that the risks of HRT outweigh the
      benefits. CONCLUSIONS: HRT is no longer routinely recommended for prevention of
      chronic disease. We present the current scientific data, benefits, risks, and
      consequent clinical recommendations regarding HRT use in postmenopausal women.

PMID- 15249240
TI  - Modulation of human leukocyte antigen-DR on monocytes and CD16 on granulocytes in
      patients with septic shock using hemoperfusion with polymyxin B-immobilized
      fiber.
AB  - BACKGROUND: Hemoperfusion with PMX-F (polymyxin B covalently immobilized on
      fibers) has been reported to be safe and effective for patients with septic
      shock. However, the molecular mechanism of this usefulness is not yet clear. The
      purpose of this study was to evaluate whether the expression of CD14, human
      leukocyte antigen (HLA)-DR on monocytes, and the expression of CD16, CD11b/CD18
      on neutrophils, are altered in septic patients according to the severity, and
      whether PMX-F treatment affects the clinical parameters and the expression of
      leukocyte surface antigen expression. PATIENTS AND METHODS: Thirty-four patients
      who were taken to the National Defense Medical College hospital at emergency, and
      who had an identified focus of infections, were enrolled in this study. The
      patients were divided into three groups: non-systemic inflammatory response
      syndrome [SIRS]) group, sepsis group, and septic shock group. Peripheral blood
      samples were collected at the time of admission to our hospital. The CD14, HLA-DR
      expression on monocytes and the CD11b/CD18, CD16 expression on granulocytes were
      evaluated using flowcytometry, and the serum interleukin (IL)-6 and IL-10 levels
      were measured using enzyme-linked immunosorbent assay. Treatment with a PMX-F
      column was performed in 10 patients with septic shock. RESULTS: The HLA-DR
      expression on monocytes and the CD16 intensity on granulocytes in patients with
      septic shock were significantly lower than those in patients with sepsis. The
      serum IL-6 and 10 levels in patients with septic shock were significantly higher
      than those in patients with sepsis. The mean systolic blood pressure in patients
      with septic shock was significantly increased after the PMX-F treatment;
      furthermore, the HLA-DR expression on monocytes and the CD16 intensity on
      granulocytes were significantly increased after the PMX-F treatment. The serum IL
      10 levels were significantly decreased after the PMX-F treatment. CONCLUSIONS: We
      showed that the surface antigens, HLA-DR on monocytes and CD16 on granulocytes,
      are extremely decreased in patients with septic shock, and that PMX-F treatment
      is effective for beneficially increasing the surface antigen expression on
      leukocytes. This therapy might be a new strategy for helping patients recover
      from immunoparalysis in septic conditions.

PMID- 15249241
TI  - Animate advanced laparoscopic courses improve resident operative performance.
AB  - BACKGROUND: The use of animate training laboratories have been touted as an
      important part of a surgical resident's training. This study determines if there
      was any benefit in resident performance and whether that benefit persisted.
      METHODS: Twelve senior surgical residents attended a course in advanced
      laparoscopy with didactic and laboratory components. The residents' skills were
      tested by having them perform a laparoscopic fundoplication before, immediately
      after, and 6 months after the course. The procedure was videotaped, and divided
      into stages that were timed and scored by a single, masked observer. RESULTS:
      Overall performance score was 35.7 +/- 2.5 for the pretest, improving to 16.5 +/-
      1.2 (P <0.05) immediately after the course, and 23.7 +/- 5.1 (P <0.05) at 6
      months. Significant improvements were seen with trocar insertion, crural closure,
      division of short gastric arteries, and fundoplication. CONCLUSIONS: The data
      presented demonstrate significant and persistent improvement in laparoscopic
      operative skills as a result of focused laboratory skill training.

PMID- 15249242
TI  - What predicts surgical internship performance?
AB  - BACKGROUND: Variables associated with postgraduate year 1 (PGY-l) performance in
      surgical training have not been fully defined. METHODS: Mean composite PGY-l
      evaluation scores were calculated from responses to questionnaires mailed to
      surgical program directors of 87 surgical graduates from 1997 to 2001. We
      analyzed evaluation scores for associations with sex, surgical specialty choice,
      United States Medical Licensing Examination (USMLE) step 1 and step 2 scores,
      Alpha Omega Alpha (AOA) election, and third-year clerkships' grade point average
      (GPA). RESULTS: There were significant first-order associations between PGY-l
      performance evaluation score and each of USMLE step 2 score and GPA. In a
      multiple linear regression model that included sex, surgical specialty choice,
      USMLE step l and step 2 scores, AOA, and GPA, USMLE step 2 score was the only
      significant predictor of PGY-l performance. CONCLUSIONS: Multiinstitutional
      studies are warranted to determine the predictive value of USMLE step 2 scores in
      residency performance beyond PGY-l and to identify other predictors of surgical
      PGY-l performance.

PMID- 15249243
TI  - A case of rapid intrahepatic dissemination of hepatocellular carcinoma after
      radiofrequency thermal ablation.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a novel technique for the treatment
      of liver malignancies that is becoming increasingly more popular because of its
      feasibility, effectivity, repeatability, and safety. However, an increased number
      of complications after RFA has been reported in literature. The aim of this paper
      is to discuss the possible role of RFA in rapid intrahepatic spreading of
      hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We treated a 66-year-old
      woman who had a 3.5-cm HCC with two courses of percutaneous RFA using a modified
      needle with seven hooks. The effectiveness of the treatment was assessed 1 month
      later by enhanced computed tomography. RESULTS: Two courses of treatment were
      needed owing to the nodule position (close to the inferior vena cava). Computed
      tomography scan performed 1 month after the second RFA showed an intrahepatic
      arteriovenous fistula. Angiography performed after 1 month showed a rapid
      intrahepatic spreading of HCC. CONCLUSIONS: Radiofrequency ablation can create an
      arteriovenous fistula that can facilitate migration of tumoral cells from the
      nodule to the hepatic portal system and rapid intrahepatic dissemination of HCC.

PMID- 15249244
TI  - Replacement of in situ saphenous venous aneurysms with arterial autografts.
AB  - BACKGROUND: Aneurysm formation in arterialized autologous saphenous veins is an
      unusual complication of in situ femoral popliteal bypass procedures. METHODS: In
      a personal series of 207 in situ saphenous femoral popliteal bypass operations,
      three nonanastomatic venous aneurysms occurred. All three venous aneurysms
      occurred in male patients who had no adequate autologous vein available as an
      interposition graft. The use of eversion endarterectomized superficial femoral
      artery is reported as a substitute interposition graft with long-term results.
      RESULTS: In the 3 male patients in this series, nonanastomatic aneurysms
      developed in their in situ saphenous femoral popliteal bypass grafts. The venous
      aneurysms developed between 5 and 8 years after the original surgical procedure.
      No adequate vein was available as a replacement for the excised venous aneurysm.
      Prosthetic conduit was not used owing to the remote possibility of a subclinical
      infection. A segment of eversion thromboendarectomized superficial femoral artery
      removed from the same leg was used as a replacement interposition graft in each
      patient. The in situ venous graft with the autologous interposition
      thromboendarterectomized superficial femoral artery remained patent until each
      patient's death 4 to 7 years after the venous aneurysm replacement. CONCLUSIONS:
      A short segment of endarectomized superficial femoral artery has been found to be
      a novel solution for the treatment of isolated saphenous vein graft aneurysms
      when no suitable vein is available. These patients should be maintained on
      lifelong aspirin therapy owing to the thrombogenic potential of endarectomized
      artery.

PMID- 15249245
TI  - Positron-emission tomography with fluorine-18-fluoro-2-deoxy-D-glucose for
      gallbladder cancer diagnosis.
AB  - BACKGROUND: Recent advances in hepatobiliary surgery have underscored the need
      for presurgical diagnosis of gallbladder cancer. Frequently, clinical
      presentation, biochemical analysis, and structural ultrasound or computed axial
      tomography images do not enable definitive differentiation of cholecystitis or
      cholethiasis from gallbladder cancer. The aim of this study was to evaluate the
      role of fludeoxy glucose-positron-emission tomography (FDG-PET) in establishing
      the benign or malignant nature of gallbladder lesions. METHODS: A case series of
      16 patients with clinical symptoms suggestive of biliary colic or chronic
      cholecystitis and with inconclusive ultrasound and/or computed axial tomography
      findings for presence of gallbladder cancer were studied by FDG-PET. RESULTS: FDG
      PET showed a sensitivity of 0.80, a specificity of 0.82, and positive and
      negative predictive values of 0.67 and 0.90, respectively. There was 1 false-
      negative result in 1 patient with mucinous adenocarcinoma and 2 false-positive
      results in 1 patient with tuberculoid granulomatous reaction and 1 patient with
      polypoid lesion with adenomyomatosis. CONCLUSIONS: FDG-PET may be of utility to
      establish the diagnosis of gallbladder cancer in patients with nonspecific
      clinical and imaging findings.

PMID- 15249246
TI  - Defecatory malfunction caused by motility disorder of the neorectum after
      anterior resection for rectal cancer.
AB  - BACKGROUND: The correlation between postoperative defecatory status after
      anterior resection for rectal cancer and physiologic neorectal motility has not
      been well delineated. METHODS: Sixty patients who underwent anterior resection
      were examined. Motility of the neorectum was examined with 4-sensor intraluminal
      pressure monitoring, and segmental colonic transit time was determined with
      radiopaque Sitzmarks (Konsyl, Fort Worth, Texas) capsules. RESULTS: Twenty-eight
      patients experienced loss of propagated contraction waves down to the neorectum,
      which was closely correlated with a prolonged transit time through the neosigmoid
      colon and neorectum. In 26 patients, minor spastic waves were observed at the
      neorectum, which did not correlate well with the loss of propagated waves. The
      loss of propagation and the existence of spastic waves were significantly
      correlated with urgency of defecation and multiple evacuations. The latter was
      also associated with major soiling and with patients' assessments of impaired
      defecatory function. CONCLUSIONS: The physiologic motility of the neorectum is
      one of the factors responsible for postoperative defecatory function after
      anterior resection for rectal cancer.

PMID- 15249247
TI  - Endoscopic treatment or surgery for undifferentiated early gastric cancer?
AB  - BACKGROUND: Although almost all (96%) the surgical cases of undifferentiated
      intramucosal early gastric cancer (EGC) have been found not to have lymph node
      metastasis (LNM), local treatment by endoscopic mucosal resection (EMR) is not
      accepted as an alternative treatment to surgery for this type of EGC. If a
      subgroup of patients with undifferentiated EGC with negligible risk of LNM can be
      defined, unnecessary surgery can be avoided. This study was conducted to
      determine this subgroup among undifferentiated EGC patients in whom the risk of
      LNM can be highly ruled out in an attempt to identify candidates who can be
      treated by EMR. METHODS: Data from 175 patients surgically resected for
      undifferentiated EGC were retrospectively collected, and clinicopathological
      factors were multivariately analyzed to identify predictive factors for LNM.
      RESULTS: Multivariate logistic regression analysis identified two independent
      risk factors for LNM, namely, a large tumor (>/=20 mm, P = 0.011) and presence of
      lymphatic involvement (P = 0.0005). Using these two risk factors as the
      predictive factors, LNM was observed in 5.8% of patients who had neither of the
      two predictive factors, whereas 23.1% or 13.1% of patients with one or two
      predictive factors had LNM, respectively. In contrast, the LNM rate was
      calculated to be 60% in patients who had both factors. Lymph node metastasis was
      not found in any of 6 patients with small intramucosal lesions (<10 mm) without
      lymphatic involvement. CONCLUSIONS: An intramucosal undifferentiated EGC that is
      smaller than 10 mm without lymphatic involvement can safely be treated by EMR
      alone, given the negligible possibility of LNM. When histological examination of
      endoscopically resected specimens shows lymphatic involvement or unexpectedly
      larger tumor size than that determined at pre-EMR endoscopic diagnosis, an
      additional surgical procedure should be considered.

PMID- 15249248
TI  - Cherry pit ingestion leading to diagnosis of colon carcinoma.

PMID- 15249249
TI  - Polypoid lesions of the gallbladder.
AB  - BACKGROUND: Polypoid lesions of the gallbladder encompass a wide variety of
      pathology. Although most of these lesions are benign, some early carcinomas of
      the gallbladder do present as polypoid lesions. Problems remain in selecting
      patients with polypoid lesions of the gallbladder for surgery, the operative
      approach, and the method of follow-up of those deemed not needing surgery. DATA
      SOURCES: This review was done by Medline search of the English literature by the
      keywords "polypoid lesions of gallbladder," "gallbladder polyps," "carcinoma of
      gallbladder," and "benign tumors of gallbladder." CONCLUSIONS: Most small
      polypoid lesions of the gallbladder are benign and remain static for years. Three
      to six-monthly ultrasonography examination is warranted in the initial follow-up
      period but it is probably unnecessary after 1 or 2 years. Age more than 50 years
      and size of polyp more than 1 cm are the two most important factors predicting
      malignancy in polypoid lesions of the gallbladder. Other risk factors include
      concurrent gallstones, solitary polyp, and symptomatic polyp. Laparoscopic
      cholecystectomy is the treatment of choice unless the suspicion of malignancy is
      high, in which case it is advisable to have open exploration, intraoperative
      frozen section, and preparation for extended resection.

PMID- 15249250
TI  - Giant extragastrointestinal stromal tumor.

PMID- 15249251
TI  - Locating the axillary vein and preserving the medial pectoral nerve.
AB  - The exposure for an axillary dissection has become more limited as surgical
      treatment for breast cancer has evolved from a radical mastectomy to a limited
      axillary dissection. Exposure of the axillary vein is made more difficult by the
      smaller incisions, by preservation of intercostobrachial nerves, and by the
      induration resulting from a previous sentinel node biopsy. To assist in the
      identification of the axillary vein, I describe the course of a visible but small
      vein adjacent to the medial pectoral nerve. The vein can be easily identified at
      the lateral edge of the pectoralis major. It, frequently together with the medial
      pectoral nerve, traverses in a craniomedial direction and leads to either the
      lateral thoracic vein (near its junction with the axillary vein) or directly to
      the axillary vein. Dissection of this vessel identifies the axillary vein,
      preserves the medial pectoral nerve and allows a more complete and safe level II
      dissection.

PMID- 15249252
TI  - Stapled-wedge Collis gastroplasty for the shortened esophagus.
AB  - BACKGROUND: Minimally invasive Collis gastroplasty is an established technique
      for managing the shortened esophagus. The purpose of this report is to describe
      our new technique, the wedge gastroplasty, and report the short-term outcomes.
      METHODS: All patients (n = 143) undergoing laparoscopic fundoplication from May
      2000 to March 2001 were assessed intraoperatively for shortened esophagus. After
      mediastinal dissection, 15 patients with inadequate intraabdominal esophageal
      length underwent wedge gastroplasty. Preoperative symptoms, operative times, and
      short-term outcomes were evaluated. RESULTS: Mean operative time was 184 +/- 36
      minutes (range 138 to 258). There was 1 cervical esophageal tear from bougie
      passage and no other minor or major complications. At 6 weeks, there was more
      improvement in esophageal symptoms compared with extraesophageal symptoms.
      CONCLUSIONS: Wedge gastroplasty is effective in decreasing symptoms in patients
      with shortened esophagus and takes less time to perform than other gastroplasty
      techniques. Further study is needed to assess long-term outcomes.

PMID- 15249253
TI  - Effect of human pancreatic juice and bile on the tensile strength of suture
      materials.
AB  - BACKGROUND: Several suture materials are used for pancreatojejunal anastomosis.
      In this study, we tested the durability of these suture materials in human
      pancreatic juice and bile. METHODS: Plain and chromic catgut, polyglactin 910,
      polyglycolic acid, polydioxanone, polypropylene, and silk sutures were incubated
      in pancreatic juice and bile that was collected from patients. Fifteen samples of
      each type of suture material were placed in human juices for 1, 3, and 7 days.
      Tensile strengths were measured with a tensionmeter. RESULTS: Plain and chromic
      catgut disintegrated in pancreatic juice and pancreatic juice plus bile mixture.
      Polyglycolic acid and polyglactin 910 suture materials were vulnerable to
      pancreatic juice within 7 days. Polydioxanone retained most of its initial
      strength in pancreatic juice and bile. Polypropylene and silk retained 84% and
      92% of their initial strength, respectively. CONCLUSIONS: We found that
      polidioxanone was the strongest suture material in pancreatic juice.

PMID- 15249254
TI  - Increases in job strain are associated with incident hypertension in the CARDIA
      Study.
AB  - BACKGROUND: Job strain, defined as high job demands and low decision latitude,
      has been associated with increased blood pressure levels in some studies, but
      most of these studies have been cross-sectional. PURPOSE: We sought to determine
      whether changes in job strain during young adulthood were associated with the
      development of hypertension, using the Coronary Artery Risk Development in Young
      Adults cohort. METHODS: A total of 3,200 employed, initially normotensive
      participants, aged 20 to 32 in 1987-1988, were followed for 8 years; the Job
      Content Questionnaire was completed twice: initially and 8 years later.
      Hypertension at follow-up was defined as systolic blood pressure (SBP) of 160 or
      higher and diastolic blood pressure of 95 mmHg or higher, or reporting being on
      antihypertensive medication. RESULTS: Job strain (based on job demands above the
      median and decision latitude below the median of the sample) was associated with
      hypertension incidence (ps <.05) for the entire cohort and among White women and
      men. Adjustment for baseline SBP, education, body mass index (BMI), change in
      BMI, and age did not alter these relations. The ratio of increasing demands
      relative to decreasing decision latitude was also associated with greater
      incidence of hypertension in the entire cohort in the multivariate model (odds
      ratio = 2.06, 95% confidence interval = 1.01-4.26). CONCLUSIONS: An increase in
      job strain is associated with incident hypertension, particularly among Whites.

PMID- 15249255
TI  - Developmental, gender, and ethnic group differences in moods and ambulatory blood
      pressure in adolescents.
AB  - BACKGROUND: Adolescence is characterized by profound changes in physical,
      psychological, and social functioning thought to be accompanied by intense and
      varying moods. PURPOSE: Within a psychophysiological framework, this study
      examined the prevalence of 12 self-reported mood states of adolescents;
      investigated associations between specific mood states and ambulatory blood
      pressure readings; and explored effects of interactions among moods, gender,
      ethnic group, and maturation on ambulatory blood pressures. METHODS: The sample
      included 371 African American, European American, and Hispanic American
      adolescents 11 to 16 years old. Systolic (SBP) and diastolic (DBP) blood
      pressures were measured every 30 min with an ambulatory monitor and were
      synchronized with electronic activity monitoring and moods self-recorded during
      waking hours in a checklist diary. RESULTS: Moods differed significantly by
      gender, ethnic group, and maturation. Controlling for height, maturation, gender,
      ethnic group, mother's education, position, location, activity, other moods, and
      interactions of moods with other variables in a multilevel, random coefficients
      regression model, both positive and negative mood states were associated with
      higher levels of SBP and DBP; being relaxed or bored, or having a feeling of
      accomplishing things were associated with lower SBP and DBP. There were
      significant interaction effects of moods with physical maturity, gender, and
      ethnic group on ambulatory SBP and DBP. CONCLUSIONS: Further study of the
      modifying effects of gender, ethnic group, and stage of development on reports of
      moods, and their associations with cardiovascular responses is recommended.

PMID- 15249256
TI  - Socioeconomic status and perceptions of access and safety for physical activity.
AB  - BACKGROUND: Environmental factors may play an important role on influencing
      physical activity (PA) behaviors. PURPOSE: Perceptions of access and safety for
      PA were compared among residents who were stratified as low or high in
      socioeconomic status (SES). METHODS: Residents of a U.S. southeastern county (N =
      1,194, 18-96 years of age) were contacted using a random-digit-dial method and
      asked about neighborhood and community environmental supports for PA. A
      Geographic Information System (GIS) was used to identify trails, sidewalks,
      public recreation facilities, and violent crime incidents. RESULTS: A cluster
      analysis identified 10 census tracts as low SES and 11 census tracts as high SES
      (median household income, owner-occupied houses). More African Americans (66.5%)
      than Whites (33.5%) were classified as living in low-SES areas. Respondents from
      low-SES areas also reported engaging in less PA based on Centers for Disease
      Control and Prevention and American College of Sports Medicine recommendations
      than respondents from high-SES areas (p <.05). Respondents from low-SES (vs. high
      SES) areas reported higher perceptions of neighborhood crime, unattended dogs,
      unpleasantness of neighborhoods, untrustworthy neighbors, and less access to
      public recreation facilities (ps <.05). GIS data for presence of sidewalks,
      recreation facilities, and crime did not support these differences in
      perceptions; however, respondents from low-SES (vs. high-SES) areas had
      substantially fewer trails. Having and using trails in one's community predicted
      sufficient PA and walking for 150 min/week for low-SES respondents but not for
      high SES respondents (ps =.05, adjusted for covariates). CONCLUSIONS: Having
      access to trails is an important environmental feature among low-SES communities
      and should be the focus of future community-based PA interventions.

PMID- 15249257
TI  - Social relationships and physiological function: the effects of recalling social
      relationships on cardiovascular reactivity.
AB  - BACKGROUND: The mechanisms by which social relationships exert their influence on
      mental and physical health outcomes deserve greater attention. PURPOSE: Although
      many studies assess the influence of actual social interactions on cardiovascular
      reactivity, we hypothesized that cognitive and behavioral processes (e.g.,
      recalling and discussing relationships) may be important factors responsible for
      the health effects of social relationships. METHODS: We had men and women recall
      and speak about specific relationships that differed in their underlying positive
      and negative substrates. RESULTS: Results revealed that gender moderated the
      hypothesized pattern of responses, with women showing consistently greater
      cardiovascular reactivity to the speaking task, particularly when speaking about
      negative relationships, compared to men. CONCLUSIONS: This study is discussed in
      light of recent research on gender differences in relationship outcomes as well
      as the potential importance of delineating the cognitive representations and
      processes that influence reactions to one's social environment.

PMID- 15249258
TI  - Health-related quality of life in a multiethnic sample of breast cancer
      survivors.
AB  - BACKGROUND: Little is known about the experiences of women from varying ethnic
      groups following treatment for breast cancer. PURPOSE: This study provides a
      comprehensive description of health-related quality of life (HRQL) and identifies
      problem areas and predictive factors for a multiethnic sample. METHODS: Six
      hundred twenty-one breast cancer survivors from 2 major cities participated
      within 5 years of their diagnosis. Participants were African Americans, Latinas,
      Asian Americans, and Whites. Patients filled out questionnaire packets comprising
      standardized instruments related to HRQL, psychological adjustment, cancer
      related treatment, and demographic variables. Data were analysed using 2 methods:
      (a) observation of findings prior to controlling for demographic and treatment
      variables and (b) observation of findings after controlling for variables
      confounded with ethnicity. RESULTS: Findings indicate that most women experienced
      good HRQL. Group differences revealed that African Americans found more meaning
      in life as a result of having breast cancer, and Latinas reported more physical
      symptoms. Age predicted aspects of HRQL for African Americans and Whites.
      CONCLUSIONS: This study comprehensively assessed HRQL following breast cancer for
      ethnic minority women. Most breast cancer survivors in this study reported levels
      of HRQL comparable to established norms. However, some quality of life
      impediments surfaced in particular groups. Researchers should not assume that
      predictive models of breast cancer HRQL are the same across ethnic groups.

PMID- 15249259
TI  - Group-mediated activity counseling and traditional exercise therapy programs:
      effects on health-related quality of life among older adults in cardiac
      rehabilitation.
AB  - BACKGROUND: Regular physical activity has been consistently related to
      improvements in health- related quality of life (HRQL) in older adults.
      Nevertheless, systematic investigations of the influence of exercise therapy on
      older men and women enrolled in cardiac rehabilitation remain sparse. PURPOSE:
      The primary purpose of this investigation was to compare the effects of a group
      mediated cognitive behavioral physical activity intervention program (GMCB) to a
      traditional cardiac rehabilitation program (CRP) with regard to changes in HRQL
      in a community-dwelling sample of older adults. METHODS: This randomized clinical
      trial assigned 147 participants who were eligible for inclusion in cardiac
      rehabilitation to the GMCB or traditional CRP arms. Changes in HRQL at 3 and 12
      months were assessed using the Short Form-36 (SF-36) from the Medical Outcomes
      Study. RESULTS: Mixed-model analyses yielded significant Baseline x Gender x
      Treatment interactions for the self-reported mental health component and the
      Vitality subscale of the SF-36. Decomposition of these interactions revealed that
      men in both exercise therapy groups and women in the GMCB treatment with low
      baseline values demonstrated more favorable improvements in the HRQL perceived
      mental health measures than women in the CRP treatment. CONCLUSIONS: Improvements
      in HRQL among older adults enrolled in cardiac rehabilitation differ as a
      function of treatment, gender, and initial mental health status. Results are
      discussed in terms of the implications for the design of future physical activity
      interventions among older adults with cardiovascular disease and the measurement
      of their HRQL.

PMID- 15249260
TI  - Job characteristics, occupational status, and ambulatory cardiovascular activity
      in women.
AB  - BACKGROUND: Prior research concerning the effects of occupational status and work
      stress on ambulatory blood pressure (AmBP) has seldom included women, and
      available results are equivocal. Moreover, the concurrent effects of occupational
      status and job characteristics have rarely been investigated. Some research is
      consistent with the idea that stressful job characteristics are especially
      detrimental to health in low-status workers, creating a cumulative physiological
      burden. PURPOSE: To examine the independent and joint effects of occupational
      status and perceived demands, control, and social support at work on AmBP and
      heart rate (HR) in women. METHODS: One hundred eight women (M age = 41.07 years)
      wore an AmBP monitor for 2 days and completed a self-report assessment of job
      control, demands, and support (i.e., Karesek et al.'s Job Content Questionnaire).
      RESULTS: After controlling for numerous potential confounds, occupational status
      and job characteristics accounted for 18% and 22% of the inter-individual
      variability in ambulatory systolic blood pressure (SBP) and HR, respectively.
      Occupational status independently predicted ambulatory cardiovascular activity
      and interacted with job characteristics, particularly in relation to SBP.
      CONCLUSIONS: Inasmuch as ambulatory SBP and HR predict future cardiovascular
      morbidity and mortality, women with both lower status occupations and stressful
      job circumstances could be at disproportionately high cardiovascular risk.

PMID- 15249261
TI  - Providing a web-based online medical record with electronic communication
      capabilities to patients with congestive heart failure: randomized trial.
AB  - BACKGROUND: It is possible to provide patients with secure access to their
      medical records using the Internet. Such access may assist patients in the self
      management of chronic diseases such as heart failure. OBJECTIVE: To assess how a
      patient-accessible online medical record affects patient care and clinic
      operations. The SPPARO (System Providing Access to Records Online) software
      consisted of a web-based electronic medical record, an educational guide, and a
      messaging system enabling electronic communication between the patient and staff.
      METHODS: A randomized controlled trial was conducted in a specialty practice for
      patients with heart failure. Surveys assessing doctor-patient communication,
      adherence, and health status were conducted at baseline, 6 months, and 1 year.
      Use of the system, message volume, utilization of clinical services, and
      mortality were monitored. RESULTS: One hundred and seven patients were enrolled
      (54 intervention and 53 controls). At 12 months, the intervention group was not
      found to be superior in self-efficacy (KCCQ self-efficacy score 91 vs. 85,
      p=0.08), but was superior in general adherence (MOS compliance score 85 vs. 78,
      p=0.01). A trend was observed for better satisfaction with doctor-patient
      communication. The intervention group had more emergency department visits (20
      vs. 8, p=0.03), but these visits were not temporally related to use of the online
      medical record. There were no adverse effects from use of the system.
      CONCLUSIONS: Providing patients with congestive heart failure access to an online
      medical record was feasible and improved adherence. An effect on health status
      could not be demonstrated in this pilot study.

PMID- 15249262
TI  - Patient entry of information: evaluation of user interfaces.
AB  - BACKGROUND: Personal health records are web-based applications that allow
      patients to directly enter their own data into secure repositories in order to
      generate accessible profiles of medical information. OBJECTIVE: The authors
      evaluated a variety of user interfaces to determine whether different types of
      data entry methods employed by Personal health records may have an impact on the
      accuracy of patient-entered medical information. METHODS: Patients with disorders
      requiring treatment with thyroid hormone preparations were recruited to enter
      data into a web-based study application. The study application presented
      sequences of exercises that prompted free text entry, pick list selection, or
      radio button selection of information related to diagnoses, prescriptions, and
      laboratory test results. Entered data elements were compared to information
      abstracted from patients' clinic notes, prescription records, and laboratory test
      reports. RESULTS: Accuracy rates associated with the different data entry methods
      tested varied in relation to the complexity of requested information. Most of the
      data entry methods tested allowed for accurate entry of thyroid hormone
      preparation names, laboratory test names, and familiar diagnoses. Data entry
      methods that prompted guided abstraction of data elements from primary source
      documents were associated with more accurate entry of qualitative and
      quantitative information. CONCLUSIONS: Different types of data entry methods
      employed by Personal health records may have an impact on the accuracy of patient
      entered medical information. Approaches that rely on guided entry of data
      elements abstracted from primary source documents may promote more accurate entry
      of information.

PMID- 15249263
TI  - Reconciling the patient's role in the improvement of health outcomes: medical
      informatics' newest frontier.

PMID- 15249264
TI  - Health attitudes, health cognitions, and health behaviors among Internet health
      information seekers: population-based survey.
AB  - BACKGROUND: Using a functional theory of media use, this paper examines the
      process of health-information seeking in different domains of Internet use.
      OBJECTIVE: Based on an analysis of the 1999 HealthStyles data, this study was
      designed to demonstrate that people who gather information on the Internet are
      more health-oriented than non-users of Internet health information. METHODS: The
      Porter Novelli HealthStyles database, collected annually since 1995, is based on
      the results of nationally representative postal mail surveys. In 1999, 2636
      respondents provided usable data for the HealthStyles database. Independent
      sample t-tests and logistic regression analyses were conducted. RESULTS: The
      results showed that individuals who searched for health information on the
      Internet were indeed more likely to be health-oriented than those who did not.
      Consumers who sought out medical information on the Internet reported higher
      levels of health-information orientation and healthy activities, as well as
      stronger health beliefs than those who did not search for medical news on the
      Internet. It was observed that those who reported searching for information about
      drugs and medications on the Internet held stronger health beliefs than the non
      searchers. Comparison of individuals who reported seeking out information about
      specific diseases on the Internet with individuals who did not showed those who
      sought out disease-specific information on the Internet to be more health
      oriented. Finally, consumers who sought out healthy lifestyle information on the
      Internet were more health conscious and more health-information oriented than
      those who did not. They were also more likely to hold stronger health-oriented
      beliefs and to engage in healthy activities. CONCLUSIONS: The results support the
      functional theory of Internet use. Internet searchers who used the Internet for a
      wide range of health purposes were typically more health oriented than non
      searchers.

PMID- 15249265
TI  - Improvement of the educational process by computer-based visualization of
      procedures: randomized controlled trial.
AB  - BACKGROUND: Before any invasive procedure, physicians have a legal obligation to
      inform patients. Traditionally, this involves a discussion with a physician,
      supplemented by written leaflet information directed at the specific procedure.
      OBJECTIVE: Comparison of the use and effectiveness of computer-based
      visualization opposed to standardized conversation for providing patients with
      information of forthcoming procedures (coronary catheters or endoscopy
      procedures). METHODS: Prospective, randomized trial with 56 participants
      allocated in two different groups: Visualization Group (standardized information
      supported by a tool for displaying two-dimensional pictures to explain medical
      facts as well as informative leaflet) or Control Group (standardized information
      and informative leaflet only). Detailed information was given about the
      indication, the probable complications and the details of the forthcoming
      procedures (coronary catheters or endoscopy procedures). All participants had to
      reach a Karnofsky Score of 70 points and be able to understand German or English.
      Main outcome measures were patient's satisfaction with physician-patient
      conversation, patient's acquired knowledge and duration of the intervention as
      described above. RESULTS: Patients of the Visualization Group were more satisfied
      with the conversation and had higher knowledge scores after the conversation. A
      Mann-Whitney-U-Test between the two groups showed that these differences in
      satisfaction (P<0.001) and knowledge (P= or <0.006) were statistically
      significant. Length of time needed for the conversation was slightly higher in
      the Visualization Group, but this difference was not statistically significant
      (25 versus 23 min; P= 0.441). No differences could be found due to differing age
      or educational level in the results of the Visualization and the Control Group.
      CONCLUSIONS: Using computerized visualization increased the satisfaction and
      knowledge of the patients. The presentation of the visualized information in the
      Visualization Group did not demand significantly more time than the standard
      conversation in the Control Group.

PMID- 15249266
TI  - First evaluation of the NHS direct online clinical enquiry service: a nurse-led
      web chat triage service for the public.
AB  - BACKGROUND: NHS Direct is a telephone triage service used by the UK public to
      contact a nurse for any kind of health problem. NHS Direct Online (NHSDO) extends
      NHS Direct, allowing the telephone to be replaced by the Internet, and
      introducing new opportunities for informing patients about their health. One
      NHSDO service under development is the Clinical Enquiry Service (CES), which uses
      Web chat as the communication medium. OBJECTIVE: To identify the opportunities
      and possible risks of such a service by exploring its safety, feasibility, and
      patient perceptions about using Web chat to contact a nurse. METHODS: During a
      six-day pilot performed in an inner-city general practice in Coventry, non-urgent
      patients attending their GP were asked to test the service. After filling out
      three Web forms, patients used a simple Web chat application to communicate with
      trained NHS Direct triage nurses, who responded with appropriate triage advice.
      All patients were seen by their GP immediately after using the Web chat service.
      Safety was explored by comparing the nurse triage end point with the GP's
      recommended end point. In order to check the feasibility of the service, we
      measured the duration of the chat session. Patient perceptions were measured
      before and after using the service through a modified Telemedicine Perception
      Questionnaire (TMPQ) instrument. All patients were observed by a researcher who
      captured any comments and, if necessary, to assisted with the process. RESULTS: A
      total of 25 patients (mean age 48 years; 57% female) agreed to participate in the
      study. An exact match between the nurse and the GP end point was found in 45%
      (10/22) of cases. In two cases, the CES nurse proposed a less urgent end point
      than the GP. The median duration of Web chat sessions was 30 minutes, twice the
      median for NHS Direct telephone calls for 360 patients with similar presenting
      problems. There was a significant improvement in patients' perception of CES
      after using the service (mean pre-test TMPQ score 44/60, post-test 49/60; p=0.008
      (2-tailed)). Patients volunteered several potential advantages of CES, such as
      the ability to re-read the answers from the nurse. Patients consider CES a useful
      addition to regular care, but not a replacement for it. CONCLUSIONS: Based on
      this pilot, we can conclude that CES was sufficiently safe to continue piloting,
      but in order to make further judgments about safety, more tests with urgent cases
      should be performed. The Web chat sessions as conducted were too long and
      therefore too expensive to be sustainable in the NHS. However, the positive
      reaction from patients and the potential of CES for specific patient groups (the
      deaf, shy, or socially isolated) encourage us to continue with piloting such
      innovative communication methods with the public.

PMID- 15249267
TI  - Setting the public agenda for online health search: a white paper and action
      agenda.
AB  - BACKGROUND: Searches for health information are among the most common reasons
      that consumers use the Internet. Both consumers and quality experts have raised
      concerns about the quality of information on the Web and the ability of consumers
      to find accurate information that meets their needs. OBJECTIVE: To produce a
      national stakeholder-driven agenda for research, technical improvements, and
      education that will improve the results of consumer searches for health
      information on the Internet. METHODS: URAC, a national accreditation
      organization, and Consumer WebWatch (CWW), a project of Consumers Union (a
      consumer advocacy organization), conducted a review of factors influencing the
      results of online health searches. The organizations convened two stakeholder
      groups of consumers, quality experts, search engine experts, researchers, health
      care providers, informatics specialists, and others. Meeting participants
      reviewed existing information and developed recommendations for improving the
      results of online consumer searches for health information. Participants were not
      asked to vote on or endorse the recommendations. Our working definition of a
      quality Web site was one that contained accurate, reliable, and complete
      information. RESULTS: The Internet has greatly improved access to health
      information for consumers. There is great variation in how consumers seek
      information via the Internet, and in how successful they are in searching for
      health information. Further, there is variation among Web sites, both in quality
      and accessibility. Many Web site features affect the capability of search engines
      to find and index them. CONCLUSIONS: Research is needed to define quality
      elements of Web sites that could be retrieved by search engines and understand
      how to meet the needs of different types of searchers. Technological research
      should seek to develop more sophisticated approaches for tagging information, and
      to develop searches that "learn" from consumer behavior. Finally, education
      initiatives are needed to help consumers search more effectively and to help them
      critically evaluate the information they find.

PMID- 15249268
TI  - Web content accessibility of consumer health information web sites for people
      with disabilities: a cross sectional evaluation.
AB  - BACKGROUND: The World Wide Web (WWW) has become an increasingly essential
      resource for health information consumers. The ability to obtain accurate medical
      information online quickly, conveniently and privately provides health consumers
      with the opportunity to make informed decisions and participate actively in their
      personal care. Little is known, however, about whether the content of this online
      health information is equally accessible to people with disabilities who must
      rely on special devices or technologies to process online information due to
      their visual, hearing, mobility, or cognitive limitations. OBJECTIVE: To
      construct a framework for an automated Web accessibility evaluation; to evaluate
      the state of accessibility of consumer health information Web sites; and to
      investigate the possible relationships between accessibility and other features
      of the Web sites, including function, popularity and importance. METHODS: We
      carried out a cross-sectional study of the state of accessibility of health
      information Web sites to people with disabilities. We selected 108 consumer
      health information Web sites from the directory service of a Web search engine. A
      measurement framework was constructed to automatically measure the level of Web
      Accessibility Barriers (WAB) of Web sites following Web accessibility
      specifications. We investigated whether there was a difference between WAB scores
      across various functional categories of the Web sites, and also evaluated the
      correlation between the WAB and Alexa traffic rank and Google Page Rank of the
      Web sites. RESULTS: We found that none of the Web sites we looked at are
      completely accessible to people with disabilities, i.e., there were no sites that
      had no violation of Web accessibility rules. However, governmental and
      educational health information Web sites do exhibit better Web accessibility than
      the other categories of Web sites (P < 0.001). We also found that the correlation
      between the WAB score and the popularity of a Web site is statistically
      significant (r = 0.28, P < 0.05), although there is no correlation between the
      WAB score and the importance of the Web sites (r = 0.15, P = 0.111). CONCLUSIONS:
      Evaluation of health information Web sites shows that no Web site scrupulously
      abides by Web accessibility specifications, even for entities mandated under
      relevant laws and regulations. Government and education Web sites show better
      performance than Web sites among other categories. Accessibility of a Web site
      may have a positive impact on its popularity in general. However, the Web
      accessibility of a Web site may not have a significant relationship with its
      importance on the Web.

PMID- 15249269
TI  - Do the leading children's hospitals have quality web sites? A description of
      children's hospital web sites.
AB  - BACKGROUND: Although leading children's hospitals are recognized as preeminent in
      the provision of health care to children, the quality of their Web sites has not
      been described. OBJECTIVE: To describe technical characteristics of the Web sites
      of leading children's hospitals. METHODS: This is a cross-sectional descriptive
      infodemiology study. Two reviewers independently reviewed and analyzed the Web
      sites of 26 nationally prominent children's hospitals in June 2003, using
      objective criteria based on accessibility (based on age and language),
      attribution, completeness, credibility, currency, disclosure, readability, and
      other technical elements. RESULTS: One-third of Web sites included content for
      children and adolescents. Twenty-four (92%) of the Web sites had health and
      disease-specific information. One-third contained only English, while two-thirds
      included other languages. All 26 Web sites included a disclaimer, although none
      had a requirement to read the disclaimer before accessing health and disease
      specific information. Twenty-four (92%) had search options. Although most (85%)
      listed a copyright date, only 10% listed the date last updated. CONCLUSIONS: This
      is the first study to examine the Web sites of leading children's hospitals.
      Although the Web sites were designed for children's hospitals, only a few sites
      included content for children and adolescents. Primary care physicians who refer
      patients to these sites should be aware that many have limited content for
      children, and should assess them for other limitations, such as inconsistent
      documentation of disclaimers or failure to show the date of the last Web site
      update. These Web sites are a potentially useful source of patient information.
      However, as the public increasingly looks to the Internet for health information,
      children's hospitals need to keep up with increasingly high standards and demands
      of health-care consumers.

PMID- 15249271
TI  - The expanding role of neuropsychology in geriatric psychiatry.

PMID- 15249270
TI  - Efficacy of quality criteria to identify potentially harmful information: a cross
      sectional survey of complementary and alternative medicine web sites.
AB  - BACKGROUND: Many users search the Internet for answers to health questions.
      Complementary and alternative medicine (CAM) is a particularly common search
      topic. Because many CAM therapies do not require a clinician's prescription,
      false or misleading CAM information may be more dangerous than information about
      traditional therapies. Many quality criteria have been suggested to filter out
      potentially harmful online health information. However, assessing the accuracy of
      CAM information is uniquely challenging since CAM is generally not supported by
      conventional literature. OBJECTIVE: The purpose of this study is to determine
      whether domain-independent technical quality criteria can identify potentially
      harmful online CAM content. METHODS: We analyzed 150 Web sites retrieved from a
      search for the three most popular herbs: ginseng, ginkgo and St. John's wort and
      their purported uses on the ten most commonly used search engines. The presence
      of technical quality criteria as well as potentially harmful statements
      (commissions) and vital information that should have been mentioned (omissions)
      was recorded. RESULTS: Thirty-eight sites (25%) contained statements that could
      lead to direct physical harm if acted upon. One hundred forty five sites (97%)
      had omitted information. We found no relationship between technical quality
      criteria and potentially harmful information. CONCLUSIONS: Current technical
      quality criteria do not identify potentially harmful CAM information online.
      Consumers should be warned to use other means of validation or to trust only
      known sites. Quality criteria that consider the uniqueness of CAM must be
      developed and validated.

PMID- 15249272
TI  - Pharmacotherapy of bipolar disorder in old age: review and recommendations.
AB  - The authors reviewed the evidence-base for pharmacological treatment of mania and
      bipolar (BP) depression in late life. Treatment benefits and side effects may be
      modified by age-associated factors, such as neurocognitive impairments. Lithium
      and divalproex have most often been studied in elderly patients, and both may be
      efficacious in acute treatment of mania, but there are no controlled efficacy or
      effectiveness trials. The role of atypical antipsychotic agents remains to be
      clarified. Similarly, there are no systematic studies of the treatment of BP
      depression in elderly patients. The authors make suggestions for management and
      delineate priorities for research.

PMID- 15249273
TI  - Metaanalysis of randomized trials of the efficacy and safety of donepezil,
      galantamine, and rivastigmine for the treatment of Alzheimer disease.
AB  - The authors estimated the effects of each of the three commonly used drugs for
      Alzheimer disease (donepezil, galantamine, and rivastigmine) in terms of
      predefined clinical outcomes and trial completion rates, by dosing level, and
      described differences among them. Using both electronic and manual search
      strategies (January 1992 to July 2002), a metaanalysis examined the effect of the
      drugs on clinical outcomes and completion rates. Regression analyses compared the
      effect of dose on clinical outcomes and completion rates, using 10 donepezil, 6
      galantamine, and 5 rivastigmine articles. All three drugs showed beneficial
      effects on cognitive tests, as compared with placebo. For donepezil and
      rivastigmine, larger doses were associated with larger effect. This was not the
      case with galantamine. The odds of clinical global improvement demonstrated
      superiority over placebo for each drug, with no dose effects noted. Dropout rates
      were greater with galantamine and rivastigmine. There was little difference in
      dropout rate for each drug at each dose-level, except with high-dose donepezil.
      This was accounted for by the high dropout rate in two 52-week studies using
      larger doses. In summary, all three drugs had similar cognitive efficacy, with
      donepezil and rivastigmine showing a dose effect across the dosing levels
      studied. However, both galantamine and rivastigmine were associated with a
      greater risk of trial dropout than placebo, especially at higher dosing levels.

PMID- 15249274
TI  - Tennessee Williams.
AB  - Tennessee Williams was one of the greatest American playwrights of all time. Born
      into a family with a strong history of serious mental illness, Williams seemed to
      have had several major depressive episodes during his early adulthood, along with
      severe and worsening alcohol and drug dependence and abuse involving sedatives
      and stimulants throughout his adult life. He received treatment of variable
      quality and duration in middle and old age. Despite his mental illness, Williams
      continued to be a productive writer even after age 60, although his later works
      were less successful. The authors consider both the strengths and limitations of
      Williams' coping mechanisms.

PMID- 15249275
TI  - Stability and functional correlates of memory-based classification in older
      schizophrenia patients.
AB  - OBJECTIVE: There is an increasing interest in the usefulness of neurocognitive
      subtyping of schizophrenia. The classification of schizophrenia patients with
      cortical versus subcortical impairments has recently been validated with both
      neuropsychological and neurobiological measures. The authors examined the
      stability and correlations of these classifications with longitudinal assessments
      in older, chronically ill schizophrenia patients. METHODS: Older, chronically ill
      patients (N=589) were classified on the basis of their baseline profile, and a
      subset (N=243) was followed for periods up to 8 years, with data analyses
      conducted to evaluate the stability of these profiles, to determine whether
      classification into cortical or subcortical impairment at baseline predicts
      changes in self-care and social functioning at endpoint, up to 8 years later.
      RESULTS: Cortical profiles were most common and most stable over time, with the
      majority of patients with a subcortical profile at baseline found to have a
      cortical profile at follow-up. Those patients whose subcortical impairment
      profile was stable over time had less severe cognitive and functional impairments
      at baseline than those whose profile was found to be cortical at follow-up.
      DISCUSSION: Cortical profiles of memory impairment were associated with
      substantial cognitive impairments at baseline and did not predict risk for
      subsequent cognitive decline, whereas subcortical profiles were associated with
      worsening of cognitive impairments in about half of the cases. Those patients
      with more severe negative symptoms and cognitive and functional impairments
      within the subcortical group were most likely to decline.

PMID- 15249276
TI  - Executive functioning, illness course, and relapse/recurrence in continuation and
      maintenance treatment of late-life depression: is there a relationship?
AB  - OBJECTIVE: The authors tested the hypothesis that impaired executive functioning
      leads to high rates of relapse and recurrence in late-life depression. METHODS:
      They analyzed data from subjects participating in two independent intervention
      trials. Study I included 53 elderly depressed patients who participated in an
      open trial comparing the efficacy of paroxetine and nortriptyline and recurrence
      prevention over 18 months. Study II focused on 146 elderly depressed patients who
      received open treatment with paroxetine in a relapse-prevention study over 4
      months of continuation treatment. They examined the effect of cognitive
      functioning, in general, and executive functioning, in particular, on time-to
      relapse/recurrence, using baseline and post-treatment measures of
      neuropsychological functioning. RESULTS: The associations between cognitive
      measures and both probability of, and time-to-relapse/recurrence were small and
      statistically nonsignificant. CONCLUSION: Data failed to support the hypothesis
      that cognitive impairment, in general, or executive dysfunction, in particular,
      predicts relapse or recurrence of major depression in late life. Authors
      recommend future testing of the hypothesis with detailed, comprehensive measures
      over longer periods of observation during maintenance trials.

PMID- 15249277
TI  - Cognitive rehabilitation of mildly impaired Alzheimer disease patients on
      cholinesterase inhibitors.
AB  - OBJECTIVE: The authors evaluated the efficacy of a new cognitive rehabilitation
      program on memory and functional performance of mildly impaired Alzheimer disease
      (AD) patients receiving a cholinesterase inhibitor. METHODS: Twenty-five
      participants in the Cognitive Rehabilitation (CR) condition participated in two
      45-minute sessions twice per week for 24 total sessions. CR training included
      face-name association tasks, object recall training, functional tasks (e.g.,
      making change, paying bills), orientation to time and place, visuo-motor speed of
      processing, and the use of a memory notebook. Nineteen participants in the Mental
      Stimulation (MS) condition had equivalent therapist contact and number of
      sessions, which consisted of interactive computer games involving memory,
      concentration, and problem-solving skills. RESULTS: Compared with the MS
      condition, participants in CR demonstrated improved performance on tasks that
      were similar to those used in training. Gains in recall of face-name
      associations, orientation, cognitive processing speed, and specific functional
      tasks were present post-intervention and at a 3-month follow-up. CONCLUSION: A
      systematic program of cognitive rehabilitation can result in maintained
      improvement in performance on specific cognitive and functional tasks in mildly
      impaired AD patients.

PMID- 15249278
TI  - Effects of cigarette smoking history on cognitive functioning in healthy older
      adults.
AB  - OBJECTIVE: The authors assessed the unique effect of smoking history on cognitive
      functioning after adjusting for demographic factors such as age, education, and
      gender, and presence of vascular illness. METHODS: A sample of 127 healthy older
      adults (29 men, 98 women) between the ages of 47 and 83 (mean: 66.9) were
      administered a comprehensive neuropsychological battery. Information regarding
      risk for vascular illness was assessed with a detailed self-report history and/or
      medical examination. Smoking history was gathered with a self-report
      questionnaire, and a composite score reflecting amount and duration of cigarette
      use was computed. From this composite score, three smoking groups were created:
      None-Light, Moderate, and Heavy smokers. RESULTS: Analyses of covariance, using
      age, education, gender, and vascular status as the covariates, revealed that the
      heavy smokers performed significantly poorer than the other groups on two scores
      from a test assessing executive function/problem-solving (Wisconsin Card-Sorting
      Test), but not on any of the other cognitive tests. CONCLUSIONS: Consistent with
      previous findings, smoking history did not appear to have deleterious effects on
      most cognitive domains. Heavy smoking history, however, did appear to affect
      performance on a measure of executive functioning.

PMID- 15249279
TI  - Use of the mini-mental state exam in middle-aged and older outpatients with
      schizophrenia: cognitive impairment and its associations.
AB  - OBJECTIVE: The authors examined cognitive impairment with a commonly used
      cognitive screening tool (the Mini-Mental State Exam [MMSE]) and its relationship
      to psychopathology, functional status, and other clinically relevant participant
      characteristics in 161 middle-aged and older outpatients with schizophrenia and
      86 normal-comparison participants (NCs). METHODS: Participants completed the MMSE
      and standardized rating scales of psychopathology and motor symptoms. Other
      aspects of daily functioning were also evaluated. RESULTS: Patients had worse
      mean MMSE scores than NCs; 23% of the patients, but no NCs, had MMSE totals </=24
      (a commonly used cutoff score to define impairment). Examination of the
      individual cognitive domains assessed by the MMSE showed that schizophrenia
      patients had the greatest impairment on tasks of word recall and attention. Among
      the patients, impaired MMSE performance was associated with lower education,
      living in a structured setting, being unmarried, and more severe negative
      symptoms. CONCLUSION: The MMSE was useful in detecting functionally relevant
      cognitive deficits among middle-aged and older schizophrenia patients who scored
      in the impaired range; however, those patients in the unimpaired range may still
      have subtle cognitive deficits that were not detected with the MMSE.

PMID- 15249280
TI  - Rivastigmine in Alzheimer disease: efficacy over two years.
AB  - OBJECTIVE: Beyond 6 to 9 months of treatment with cholinesterase inhibitors (ChE
      Is), there is a notable increase in the rate of cognitive decline in Alzheimer
      disease (AD) patients, and there are few longer-term studies to evaluate this
      finding. The authors examined whether the ChE-I rivastigmine continued to be
      therapeutically effective after up to 2 years of treatment in 2,010 patients with
      probable AD. METHODS: The clinical course of AD patients treated with
      rivastigmine was compared with a prediction of their course derived by a baseline
      dependent historical model of disease progression developed from data in
      untreated AD patients. Rivastigmine efficacy data came from four 6-month, placebo
      controlled, randomized, controlled trials (RCTs) and two open-label extension
      studies. Cognitive performance was assessed by various clinician- and caregiver
      rated measures. RESULTS: After 2 years on rivastigmine, there was less cognitive
      deterioration than in historical-control subjects. These effects of rivastigmine
      on cognitive performance were considered clinically meaningful relative to
      expected global decline. Treatment-emergent adverse events were the commonly-seen
      side effects of ChEIs and were similar in frequency to those seen in patients
      assigned to shorter-term rivastigmine therapy. CONCLUSION: Rivastigmine had a
      beneficial effect on cognitive performance for up to 2 years in patients with AD,
      versus no treatment or placebo treatment in historical-control subjects.
      Caregiver and clinician assessments indicated that the cognitive performance
      findings were of a magnitude relevant to global patient functioning. Rivastigmine
      remained safe over this 2-year treatment period.

PMID- 15249281
TI  - Cognitive effects of exogenous melatonin administration in elderly persons: a
      pilot study.
AB  - OBJECTIVE: Given that circadian rhythm disruption is associated with impairments
      in cognitive performance similar to those found in age-related cognitive decline,
      the authors investigated whether exogenous melatonin administration would improve
      cognitive functioning in healthy elderly subjects. METHODS: This double-blind,
      placebo-controlled pilot study assigned 26 healthy elderly subjects to receive
      either melatonin 1 mg or placebo nightly for 4 weeks. Participants completed a
      sleep questionnaire and a battery of cognitive tests at baseline and at 4 weeks.
      RESULTS: Melatonin administration improved reported morning "restedness" and
      sleep latency after nocturnal awakening, and also improved scores on the
      California Verbal Learning Test-interference subtest. CONCLUSIONS: Melatonin
      administration at a dose of 1 mg nightly may be effective in improving certain
      aspects of cognitive functioning and subjective reports of sleep quality in
      elderly subjects. It may prove to be a useful therapeutic agent in the treatment
      of age-related cognitive decline.

PMID- 15249282
TI  - Lower mortality in geriatric patients receiving risperidone and olanzapine versus
      haloperidol: preliminary analysis of retrospective data.
AB  - OBJECTIVE: The authors examined the mortality rate in geriatric patients
      receiving either haloperidol or atypical antipsychotics. METHODS: Authors tracked
      mortality over a 2-year period in patients age 65 years or older receiving
      haloperidol (N=299) or the atypical antipsychotics risperidone or olanzapine (N=
      1,254). RESULTS: Sixty-four patients in the haloperidol group (21.4%) and 61
      patients in the atypical group (4.75%) died during the 2-year study period. The
      difference was statistically significant. CONCLUSIONS: The findings suggest that
      mortality in elderly patients receiving haloperidol is significantly higher than
      in those receiving the atypical antipsychotics risperidone or olanzapine. Authors
      discuss possible causal mechanisms.

PMID- 15249283
TI  - What can the elderly do to protect themselves from the flu in addition to getting
      a flu vaccination?

PMID- 15249284
TI  - Disparities in immunizations.

PMID- 15249285
TI  - Indigent men's use of emergency departments over primary care settings.

PMID- 15249286
TI  - What can suicide researchers learn from African Americans?

PMID- 15249287
TI  - Flint Photovoice: community building among youths, adults, and policymakers.
AB  - Flint Photovoice represents the work of 41 youths and adults recruited to use a
      participatory-action research approach to photographically document community
      assets and concerns, critically discuss the resulting images, and communicate
      with policymakers. At the suggestion of grassroots community leaders, we included
      policymakers among those asked to take photographs. In accordance with previously
      established photovoice methodology, we also recruited at the project's outset
      another group of policymakers and community leaders to provide political will and
      support for implementing photovoice participants' policy and program
      recommendations. Flint Photovoice enabled youths to express their concerns about
      neighborhood violence to policymakers and was instrumental in acquiring funding
      for local violence prevention. We note salutary outcomes produced by the
      inclusion of policymakers among adults who took photographs.

PMID- 15249288
TI  - Getting the science right and doing the right science in vaccine safety.
AB  - Because of the potential for conflicts of interest, Salmon et al. propose in this
      issue the creation of an independent vaccine safety board to assume
      responsibility for assessing the safety of licensed vaccines.We believe that the
      current system at the Food and Drug Administration (FDA) and the Centers for
      Disease Control and Prevention (CDC) facilitates needed interactions between
      those involved in risk assessment and risk management, provides substantial
      safeguards against conflicts of interest, and results in sound decisions. The
      CDC, given its role in promoting immunization, may be perceived to have a greater
      potential conflict and plans to review its vaccine safety activities. Both
      agencies recognize the importance of transparency in considering vaccine safety
      and welcome the opportunity to work with the public and the medical community to
      improve the quality of scientific information and decisionmaking.

PMID- 15249289
TI  - Ethics in public health research: protecting human subjects: the role of
      community advisory boards.
AB  - Increasingly, researchers grapple with meaningful efforts to involve communities
      in research, recognizing that communities are distinct from individuals. We also
      struggle to ensure that individual participants in research are fully protected.
      Community advisory boards (CABs) offer an opportunity to adopt a relationships
      paradigm that enables researchers to anticipate and address the context in which
      communities understand risks and benefits, and individuals give consent. CABs
      provide a mechanism for community consultation that contributes to protecting
      communities and fostering meaningful research. Furthermore, CABs can help us to
      re-create informed consent as a process. It is critical that we conduct research
      to understand the role of CABs in the informed consent process.

PMID- 15249290
TI  - The standard of care debate: can research in developing countries be both ethical
      and responsive to those countries' health needs?
AB  - To avoid exploitation of host communities, many commentators argue that subjects
      must receive the best methods available worldwide. Others worry that this
      requirement may block important research intended to improve health care,
      especially in developing countries. To resolve this dilemma, we propose a
      framework for the conditions under which it is acceptable to provide subjects
      with less than the best methods. Specifically, institutional review boards should
      assume a default of requiring the "worldwide best" methods, meaning the best
      methods available anywhere in the world, in all cases.However, institutional
      review boards should be willing to grant exceptions to this default for research
      studies that satisfy the following 4 conditions: (1) scientific necessity, (2)
      relevance for the host community, (3) sufficient host community benefit, and (4)
      subject and host community non-maleficence.

PMID- 15249291
TI  - Ethics, practice, and research in public health.
AB  - Ethical issues that can arise in distinguishing public health research from
      practice are highlighted in 2 case studies--an investigation of a tuberculosis
      outbreak in a prison and an evaluation of a program for improving HIV prevention
      services. Regardless of whether such public health investigations represent
      research or practice, we see a need for ethics oversight procedures that reflect
      actual risks and enable timely responses to crises. Such oversight should
      accommodate the perspectives of persons and communities affected by public health
      threats and by governmental responses to those threats; it should further
      recognize that public health ethics is a distinct field combining bioethics,
      political philosophy, human rights, and law.

PMID- 15249292
TI  - "Only the best class of immigration": public health policy toward Mexicans and
      Filipinos in Los Angeles, 1910-1940.
AB  - Public health officials contributed to the early 20th-century campaign against
      Mexicans and Filipinos in Los Angeles. In 1914, the newly established city and
      county health departments confronted the overwhelming task of building a public
      health infrastructure for a rapidly growing population spread over a large area.
      However, for several years public health reports focused almost exclusively on
      the various infectious diseases associated with Mexican immigrants. Although the
      segregation of Mexicans was illegal in California until 1935, county officials
      established separate clinics for Whites and Mexicans during the 1920s. With
      assistance from state officials, local health authorities participated actively
      in efforts to restrict Mexican immigration throughout the 1920s and to expel both
      Mexicans and Filipinos during the 1930s.

PMID- 15249293
TI  - Can child accidents be prevented in your community?

PMID- 15249294
TI  - Donald Budd Armstrong and W. Graham Cole: early injury control advocates.

PMID- 15249295
TI  - Uncertain benefit: the public policy of approving smallpox vaccine research.
AB  - Without an accurate assessment of the prospect of bioterrorist attack, it is
      especially challenging to evaluate the protocols for testing smallpox vaccines in
      the pediatric population. Usual regulatory mechanisms cannot shepherd research
      protocols with benefits that can only be characterized as "uncertain" in the face
      of more than minimal risk. When a protocol is placed in a government forum for
      analysis, the public has a unique opportunity to debate the balancing of research
      risks and benefits on behalf of children who are unable to assent to research
      themselves, as well as to express views about vaccination policy broadly. This
      model for review of pediatric research that may be without benefit will be
      especially important as challenging studies of various vaccines against a range
      of infectious properties, such as anthrax and severe acute respiratory syndrome
      (SARS), emerge.

PMID- 15249296
TI  - Enhancing public confidence in vaccines through independent oversight of
      postlicensure vaccine safety.
AB  - The National Immunization Program of the Centers for Disease Control and
      Prevention is responsible for controlling infectious diseases through
      vaccination, but the program also plays a key role in postlicensure vaccine
      safety assessment. The time has come to separate postlicensure vaccine safety
      assessment from vaccine risk management as recommended by the National Research
      Council of the National Academy of Sciences.The National Transportation Safety
      Board offers a useful model for developing an independent National Vaccine Safety
      Board that would have the authority to leverage resources and expertise of
      various government agencies, academia, and industry to oversee postlicensure
      vaccine safety investigations. Such a board would have been useful in recent
      vaccine safety concerns, and its independence from government programs would
      ensure optimal vaccine safety and enhance public confidence in vaccines.

PMID- 15249297
TI  - Child custody determinations in cases involving intimate partner violence: a
      human rights analysis.
AB  - Intimate partner violence and child abuse are recognized both as public health
      concerns and as violations of human rights, but related government actions and
      inactions are rarely documented as human rights violations in the United States.
      Men who abuse female partners are also highly likely to abuse the children of
      these women. However, family courts are reported to often ignore risks posed by
      abusive men in awarding child custody and visitation. Battered women involved in
      child custody litigation in Massachusetts (n = 39) were interviewed. A recurring
      pattern of potential human rights violations by the state was documented,
      corresponding to rights guaranteed in multiple internationally accepted human
      rights covenants and treaties. The human rights framework is a powerful tool for
      demonstrating the need for legal, social, and political reform regarding public
      health concerns.

PMID- 15249298
TI  - Impact of PCV7 on invasive pneumococcal disease among children younger than 5
      years: a population-based study.
AB  - We examined the impact of the heptavalent pneumococcal conjugate vaccine (PCV7)
      on hospital discharge rates for invasive pneumococcal disease among Michigan
      children younger than 5 years old. After the introduction of PCV7, the hospital
      discharge rate for children younger than 1 years old was significantly lower than
      before introduction. We correlated the decreased rates with the introduction and
      rapid uptake of PCV7. Lack of change in the hospital discharge rates for other
      age groups likely represents a slower uptake of PCV7 compared with that for
      children aged younger than 1 year.

PMID- 15249299
TI  - Role of health insurance and a usual source of medical care in age-appropriate
      vaccination.
AB  - OBJECTIVES: We examined the associations of having health insurance and having a
      usual source of medical care with age-appropriate childhood vaccination. METHODS:
      Simulations were conducted with multivariate logistic regression models and a
      nationally representative sample of children to assess the likelihood of age
      appropriate vaccination. RESULTS: Simulated provision of health insurance and a
      usual source of medical care produced substantial increases in the likelihood of
      doses being received age-appropriately. Increases in the likelihood of a child's
      being up to date were also observed, but these increases typically were smaller
      than for age-appropriate vaccination. CONCLUSIONS: Changes in childhood
      vaccination status should be assessed in age-appropriate terms, because measures
      of "up to date" status may not capture the effects of immunization interventions.

PMID- 15249300
TI  - The regional immunization registry as a public health tool for improving clinical
      practice and guiding immunization delivery policy.
AB  - OBJECTIVES: We assessed the distribution of immunization records among 3 health
      care delivery sectors and the impact of a regional immunization registry on "up
      to date" rates. METHODS: Immunization registry records in 2 regions were
      categorized as having originated in private practices, community health centers,
      or public health clinics. "Up to date" rates were calculated after we
      sequentially added immunization records from the 3 sectors. RESULTS: The
      percentage of children with immunizations documented in multiple sectors
      increased with age from 7 to 24 months, and children who were seen in multiple
      sectors were more likely to be up to date. There were relative increases in "up
      to date" rates of 50% for children aged 24 months. CONCLUSIONS: The regional
      immunization registry is a powerful public health tool for increasing documented
      "up to date" rates and providing insights into patterns of immunization delivery.

PMID- 15249301
TI  - Racial/ethnic disparities in preschool immunizations: United States, 1996-2001.
AB  - OBJECTIVES: We examined current racial/ethnic differences in immunization
      coverage rates among US preschool children. METHODS: Using National Immunization
      Survey data from 1996 through 2001, we compared vaccination coverage rates
      between non-Hispanic White, non-Hispanic Black, Hispanic, and Asian preschool
      children. RESULTS: During the 6-year study period, the immunization coverage gap
      between White and Black children widened by an average of 1.1% each year, and the
      gap between White and Hispanic children widened by an average of 0.5% each year.
      The gap between White and Asian children narrowed by an average of 0.8% each
      year. CONCLUSIONS: Racial/ethnic disparities in preschool immunization coverage
      rates have increased significantly among some groups; critical improvements in
      identifying, understanding, and addressing race/ethnicity-specific health care
      differences are needed to achieve the Healthy People 2010 goal of eliminating
      disparities.

PMID- 15249302
TI  - A middle school immunization law rapidly and substantially increases immunization
      coverage among adolescents.
AB  - OBJECTIVES: This study assessed the effectiveness of a middle school vaccination
      requirement for raising second-dose measles, mumps, and rubella vaccine and
      hepatitis B vaccine coverage among adolescents. METHODS: Random-digit-dialed
      telephone surveys were conducted before (1998) and after (1999) the
      implementation of a vaccination requirement for entry into the seventh grade in
      San Diego, Calif. RESULTS: Vaccination coverage was higher among children subject
      to the vaccination requirement (seventh-grade students; 60%) than among fifth-
      and sixth-grade students 1 year before the requirement (13%, P <.001), and 8th-
      through 12th-grade students not subject to the requirement (27%, P <.0001).
      CONCLUSIONS: Middle school-entry vaccination requirements can rapidly and
      substantially raise vaccination coverage among students subject to the law.

PMID- 15249303
TI  - Vaccination and allergic disease: a birth cohort study.
AB  - OBJECTIVES: We examined the effect of vaccination for diphtheria; polio;
      pertussis and tetanus; or measles, mumps, and rubella on the incidence of
      physician-diagnosed asthma and eczema. METHODS: We used a previously established
      birth cohort in the West Midlands General Practice research database. RESULTS: We
      found an association between vaccination and the development of allergic disease;
      however, this association was present only among children with the fewest
      physician visits and can be explained by this factor. CONCLUSIONS: Our data
      suggest that currently recommended routine vaccinations are not a risk factor for
      asthma or eczema.

PMID- 15249304
TI  - Vaccine risk perception among reporters of autism after vaccination: vaccine
      adverse event reporting system 1990-2001.
AB  - OBJECTIVES: We investigated vaccine risk perception among reporters of autism to
      the Vaccine Adverse Event Reporting System (VAERS). METHODS: We conducted
      structured interviews with 124 parents who reported autism and related disorders
      to VAERS from 1990 to 2001 and compared results with those of a published survey
      of parents in the general population. RESULTS: Respondents perceived vaccine
      preventable diseases as less serious than did other parents. Only 15% of
      respondents deemed immunization extremely important for children's health; two
      thirds had withheld vaccines from their children. CONCLUSIONS: Views of parents
      who believe vaccines injured their children differ significantly from those of
      the general population regarding the benefits of immunization. Understanding the
      factors that shape this perspective can improve communication among vaccine
      providers, policymakers, and parents/patients.

PMID- 15249305
TI  - Hepatitis A incidence and hepatitis a vaccination among American Indians and
      Alaska Natives, 1990-2001.
AB  - OBJECTIVES: We assessed the effect on trends in hepatitis A incidence of the 1996
      recommendation for routine hepatitis A vaccination of American Indian/Alaska
      Native (AIAN) children. METHODS: We examined trends in hepatitis A incidence
      among AIAN peoples during 1990-2001 and vaccination coverage levels among
      children on the largest American Indian reservation. RESULTS: Hepatitis A rates
      among AIANs declined 20-fold during 1997-2001. Declines in hepatitis A incidence
      occurred among AIANs in reservation and metropolitan areas. Among 1956 children
      living on the Navajo Nation whose medical records were reviewed, 1508 (77.1%) had
      received at least one dose of hepatitis A vaccine, and 1020 (52.1%) had completed
      the vaccine series. CONCLUSIONS: Hepatitis A rates among AIAN peoples have
      declined dramatically coincident with implementation of routine hepatitis A
      vaccination of AIAN children.

PMID- 15249306
TI  - Measuring the prevalence of overweight in Texas schoolchildren.
AB  - OBJECTIVES: We describe results from year 1 of a surveillance system to monitor
      body mass index in children at the state level. METHODS: A sample of 6630
      children attending Texas public schools, weighted to represent 4th, 8th, and 11th
      grades within race/ethnic subpopulations, was assessed. Body mass index was
      calculated from measured height and weight; demographic information was obtained
      from a questionnaire. RESULTS: Prevalence of overweight was 22.4%, 19.2%, and
      15.5% for 4th-, 8th-, and 11th-grade students, respectively. Overweight
      prevalence was highest among Hispanic boys (29.5%-32.6%), fourth-grade Hispanic
      girls (26.7%), and fourth- and eighth-grade African American girls (30.8% and
      23.1%, respectively). Eleventh-grade White/other girls had the lowest prevalence
      of overweight (5.5%). CONCLUSIONS: These data confirm the increasing prevalence
      of overweight among US children, especially among Hispanic and African American
      students compared to White/other students and fourth-grade students relative to
      8th- and 11th-grade students.

PMID- 15249307
TI  - Evaluation of a community-based intervention to promote rear seating for
      children.
AB  - OBJECTIVES: We evaluated the short-term effect of a community-based effort to
      promote child rear seating in a low-income Hispanic community. METHODS: Child
      seating patterns were observed pre- and postintervention at intersections in 1
      intervention and 2 control cities. Brief interviews assessed exposure to program
      messages. RESULTS: Child rear seating increased from 33% to 49% in the
      intervention city (P <.0001), which represented a greater increase than that in
      the control cities (P <.0001). The greatest improvement was observed in
      relatively higher-income areas. Rear seating was significantly correlated with
      reported program exposure. Incentives and exposure to the program across multiple
      channels seemed to have the greatest effect. CONCLUSIONS: Independent of
      legislation, community-based programs incorporating incentives can increase child
      rear seating.

PMID- 15249308
TI  - Trends in fruit and vegetable consumption among adults in the United States:
      behavioral risk factor surveillance system, 1994-2000.
AB  - OBJECTIVES: We examined trends in fruit and vegetable consumption in the United
      States. METHODS: A 6-item food frequency questionnaire was used to assess
      consumption among 434 121 adults in 49 states and the District of Columbia who
      were sampled in random-digit-dialed telephone surveys administered in 1994, 1996,
      1998, and 2000. RESULTS: Although the geometric mean frequency of fruit and
      vegetable consumption declined slightly, the proportion of respondents consuming
      fruits and vegetables 5 or more times per day did not change. With the exception
      of the group aged 18 to 24 years, which experienced a 3-percentage-point
      increase, little change was seen among sociodemographic subgroups. CONCLUSIONS:
      Frequency of fruit and vegetable consumption changed little from 1994 to 2000. If
      increases are to be achieved, additional efforts and new strategies will be
      needed.

PMID- 15249309
TI  - Availability and perceived effectiveness of public health activities in the
      nation's most populous communities.
AB  - OBJECTIVES: We examined the availability and perceived effectiveness of 20 basic
      public health activities in the communities where most Americans reside. METHODS:
      A self-administered questionnaire was mailed to the 497 directors of US local
      health departments serving at least 100 000 residents. RESULTS: On average, two
      thirds of the 20 public health activities were performed in the local
      jurisdictions surveyed, and the perceived effectiveness rating averaged 35% of
      the maximum possible. In multivariate models, availability of public health
      activities varied significantly according to population size, socioeconomic
      measures, local health department spending, and presence of local boards of
      health. CONCLUSIONS: Local public health capacity varies widely across the
      nation's most populous communities, highlighting the need for targeted
      improvement efforts.

PMID- 15249310
TI  - Project D.A.R.E. outcome effectiveness revisited.
AB  - OBJECTIVES: We provide an updated meta-analysis on the effectiveness of Project
      D.A.R.E. in preventing alcohol, tobacco, and illicit drug use among school-aged
      youths. METHODS: We used meta-analytic techniques to create an overall effect
      size for D.A.R.E. outcome evaluations reported in scientific journals. RESULTS:
      The overall weighted effect size for the included D.A.R.E. studies was extremely
      small (correlation coefficient = 0.011; Cohen d = 0.023; 95% confidence interval
      = -0.04, 0.08) and nonsignificant (z = 0.73, NS). CONCLUSIONS: Our study supports
      previous findings indicating that D.A.R.E. is ineffective.

PMID- 15249311
TI  - Health programs in faith-based organizations: are they effective?
AB  - OBJECTIVES: We examined the published literature on health programs in faith
      based organizations to determine the effectiveness of these programs. METHODS: We
      conducted a systematic literature review of articles describing faith-based
      health activities. Articles (n = 386) were screened for eligibility (n = 105),
      whether a faith-based health program was described (n = 53), and whether program
      effects were reported (28). RESULTS: Most programs focused on primary prevention
      (50.9%), general health maintenance (25.5%), cardiovascular health (20.7%), or
      cancer (18.9%). Significant effects reported included reductions in cholesterol
      and blood pressure levels, weight, and disease symptoms and increases in the use
      of mammography and breast self-examination. CONCLUSIONS: Faith-based programs can
      improve health outcomes. Means are needed for increasing the frequency with which
      such programs are evaluated and the results of these evaluations are
      disseminated.

PMID- 15249312
TI  - All-cause and cause-specific mortality by socioeconomic status among employed
      persons in 27 US states, 1984-1997.
AB  - OBJECTIVES: We investigated mortality differences according to socioeconomic
      status (SES) for employed persons in 27 states during 1984-1997. METHODS: SES was
      determined for persons aged 35-64 years according to the "usual occupation"
      listed on their death certificates. We used US Census denominator data. RESULTS:
      For all-cause mortality, rate ratios from lowest to highest SES quartile for men
      and women were 2.02, 1.69, 1.25, and 1.00 and 1.29, 1.01, 1.07, and 1.00,
      respectively. Percentage of all deaths attributable to being in the lowest 3 SES
      quartiles was 27%. Inverse SES gradients were strong for most major causes of
      death except breast cancer and colorectal cancer. Heart disease mortality for
      highest and lowest SES quartiles dropped 45% and 25%, respectively, between 1984
      and 1997. CONCLUSIONS: Mortality differences by SES were sustained through the
      1990s and are increasing for men.

PMID- 15249313
TI  - Individual health status and racial minority concentration in US states and
      counties.
AB  - OBJECTIVES: We examined whether the positive association between mortality rates
      and racial minority concentration documented in ecological studies would be found
      for health status after control for race/ethnicity, socioeconomic status, and
      region of residence. METHODS: We estimated least squares and probit models using
      aggregate and individual health status data from the 1995, 1997, and 1999
      versions of the Current Population Survey merged with data from the US Bureau of
      the Census regarding state- and county-level racial minority concentration.
      RESULTS: Except in the case of older Whites, racial minority concentration was
      not associated with health status after control for individual characteristics
      and fixed regional factors. CONCLUSIONS: Racial minority concentration may not be
      a determinant of individual health; differential migration patterns may explain
      the anomalous result for older Whites.

PMID- 15249314
TI  - What patients expect from complementary therapy: a qualitative study.
AB  - OBJECTIVES: Complementary and alternative therapies have become popular with
      patients in Western countries. Studies have suggested motivations for patients'
      choosing a wide range of complementary therapies. Data on the expectations of
      patients who use complementary therapy are limited. We assessed the expectations
      of patients who use complementary therapy. METHODS: Patients attending a British
      National Health Service (NHS) outpatient department that provided acupuncture,
      osteopathy, and homoeopathy were asked to complete a qualitative survey. RESULTS:
      Patients expected symptom relief, information, a holistic approach, improved
      quality of life, self-help advice, and wide availability of such therapies on the
      NHS. CONCLUSIONS: Physicians' understanding of patients' expectations of
      complementary therapies will help patients make appropriate and realistic
      treatment choices.

PMID- 15249315
TI  - A historic issue of the Annals: three papers examine paracetamol in
      osteoarthritis.

PMID- 15249316
TI  - Proptosis can be the presenting feature of systemic lupus erythematosus.

PMID- 15249317
TI  - Sustained maintenance of exercise induced muscle strength gains and normal bone
      mineral density in patients with early rheumatoid arthritis: a 5 year follow up.
AB  - OBJECTIVE: To investigate at 5 years whether an initial 2 year home based
      strength training period imposes sustained effects on muscle strength, bone
      mineral density (BMD), structural joint damage, and on disease activity in
      patients with early rheumatoid arthritis (RA). METHODS: Seventy patients were
      randomised either to perform home based strength training with loads of 50-70% of
      repetition maximum (EG) or range of motion exercises (CG). Both groups were
      encouraged to take part in aerobic activities 2-3 times a week. Maximal muscle
      strength of different muscle groups was measured by dynamometers, and BMD at the
      femoral neck and lumbar spine by dual x ray densitometry. Disease activity was
      assessed by the 28 joint disease activity score, and joint damage by x ray
      findings. RESULTS: 62 patients completed 2 years' training and 59 patients
      attended check up at 5 years. Mean (SD) maximum muscle strength indices increased
      from baseline to 2 years-in EG from 212 (78) kg by a mean (95% CI) of 68 (55 to
      80) and in CG from 195 (72) kg by 35 (13 to 60) kg-and remained at that level for
      the next 3 years. Development of BMD in EG tended to be more favourable than that
      in CG. Muscle strength training was not detrimental to joint structures or
      disease activity. CONCLUSION: The patients' exercise induced muscle strength
      gains during a 2 year training period were maintained throughout a subsequent
      self monitored training period of 3 years. Despite substantial training effects
      in muscle strength, BMD values remained relatively constant. Radiographic damage
      remained low even at 5 years.

PMID- 15249318
TI  - Sequential changes of parathyroid hormone related protein (PTHrP) in articular
      cartilage during progression of inflammatory and degenerative arthritis.
AB  - OBJECTIVE: To investigate immunolocalisation of parathyroid hormone related
      protein (PTHrP) in two sequential models of experimental cartilage damage
      (inflammatory and degenerative) in order to elucidate differences in chondrocyte
      response to the disease. METHODS: Immunohistochemistry with a polyclonal rabbit
      antiserum to the N-terminal domain of PTHrP was used to detect this protein in
      two different rabbit models sharing progressive cartilage damage: antigen induced
      arthritis (AIA) and osteoarthritis (OA) secondary to partial medial meniscectomy.
      Cartilage specimens from early (2 days in AIA; 8 weeks in experimental OA) and
      late (3 weeks in AIA; 52 weeks in OA) disease were compared. RESULTS: Cell and
      matrix PTHrP staining in early AIA and OA was similar to that in controls. Late
      AIA cartilage showed a significant decrease in PTHrP positive cells and in the
      cartilage matrix. In contrast, at late OA stages, distinct PTHrP positivity was
      detected in proliferating cell clones, as assessed by proliferating cell nuclear
      antigen staining around cartilage damaged areas. CONCLUSION: PTHrP staining of
      hyaline articular cartilage shows a different pattern during progression of each
      type of arthritis: an overall decrease associated with the inflammatory disease,
      and an increase in the proliferating chondrocyte clones with degenerative
      arthritis.

PMID- 15249319
TI  - Paracetamol in osteoarthritis of the knee.
AB  - BACKGROUND: Paracetamol is a recommended symptomatic treatment of osteoarthritis
      (OA), but in clinical trials sample sizes have been relatively small and variable
      daily doses of paracetamol have been used. OBJECTIVES: To determine the
      therapeutic efficacy of paracetamol in OA of the knee and identify predictive
      factors of clinical response to treatment. METHODS: A double blind, parallel
      group, placebo controlled trial of analgesic efficacy and safety of paracetamol
      versus placebo including 779 patients with OA of the knee. Patients were randomly
      assigned to receive paracetamol 4 g/day (n = 405) or placebo (n = 374) for 6
      weeks. Symptomatic OA of the knee was required at inclusion with global pain
      intensity of the knee during physical activities for the past 24 hours of >or=30
      mm on a 100 mm visual analogue scale. The primary end point was a 30% decrease of
      global pain intensity of the knee. Intention to treat analyses were performed.
      RESULTS: The percentage of responders did not differ significantly between
      groups: 52.6% and 51.9% in paracetamol and placebo groups, respectively (p =
      0.840). In a subgroup of patients with chronic mechanical knee pain without signs
      of inflammation (n = 123), the mean change in pain intensity from baseline was
      25.2 mm v 15.2 mm, in the paracetamol (n = 63) and placebo (n = 60) groups,
      respectively-mean difference 10.0 mm; 95% CI 1.0 to 19.0; p = 0.0294. No serious
      adverse events were attributable to treatment. CONCLUSION: A statistically
      significant symptomatic effect of oral paracetamol 4 g/day over placebo was not
      found, suggesting that paracetamol use in symptomatic OA of the knee should be
      further explored. The tolerability and safety of paracetamol, at the recommended
      maximum dose of 4 g/day, was confirmed over 6 weeks.

PMID- 15249320
TI  - Bone loss in patients treated with pulses of methylprednisolone is not
      negligible: a short term prospective observational study.
AB  - OBJECTIVE: To examine the influence of intravenous pulsed methylprednisolone (MP)
      on bone mass. METHODS: 38 patients (30 women) with various rheumatic disorders
      requiring intravenous MP pulse treatment were examined at baseline and after 6
      months with dual energy x ray absorptiometry (DXA), measuring hip and lumbar
      spine bone mineral density (BMD). Demographic and clinical data were collected.
      RESULTS: Demographics showed: mean (SD) age 48.4 (16.3) years, body mass index
      24.9 (5.1) kg/m(2), and median (range) disease duration 3.2 (0.1-40.0) years.
      During follow up patients received a mean cumulative MP dose of 3.0 (1.6) g given
      as 5.7 (2.0) pulses over a median period of 5.7 (2.3-33.7) months. 34/38 (89%)
      patients were also pulsed with cyclophosphamide, 20 (53%) were taking oral
      corticosteroids, and 8 (21%) were using either bisphosphonates or oestrogen. At
      the end of the study mean BMD was reduced by -2.2% at the femoral neck, -1.1% at
      the total hip, and -1.0% at the spine L2-4. In subgroups BMD increased in
      patients treated with bisphosphonates or oestrogen (femoral neck +1.6%, total hip
      +3.2%, spine L2-4 +4.5%), whereas BMD decreased at all sites in patients not
      treated with antirersorptive treatment, both for users (femoral neck -4.4%, total
      hip -2.4%, spine L2-4 -2.1%) and non-users of concomitant oral prednisolone
      (femoral neck -1.7%, total hip -1.9%, spine L2-4 -2.6%). CONCLUSION: Treatment
      with intravenous pulses of MP leads to a high rate of bone loss. Prevention of
      bone loss in these patients with bisphosphonates and oestrogens should be
      considered.

PMID- 15249321
TI  - Quantitative ultrasound and bone mineral density: discriminatory ability in
      patients with rheumatoid arthritis and controls with and without vertebral
      deformities.
AB  - BACKGROUND: Quantitative ultrasound (QUS) is a reliable tool for discriminating
      between subjects with and without vertebral deformities in postmenopausal
      osteoporosis. Less is known about osteoporosis caused by inflammatory diseases or
      corticosteroid use. OBJECTIVES: (1). To compare in patients with rheumatoid
      arthritis the ability of QUS and dual energy x ray absorptiometry (DXA) to
      discriminate between those with and without vertebral deformities; (2). to
      explore whether the results are similar in population based controls. METHODS:
      Standardised lateral radiographs of the spine were obtained from 210 patients
      with rheumatoid arthritis aged over 50 years and 210 individually matched
      controls. Vertebral deformities were assessed morphometrically and
      semiquantitatively. All participants underwent bone measurements by DXA (Lunar
      Expert) and QUS (Lunar Achilles+). Receiver operating curve (ROC) analysis was
      used to compare the discriminating ability of BMD and QUS measurements in
      patients and controls with and without vertebral deformities. Analyses were
      repeated in patients stratified according to corticosteroid use. RESULTS: For all
      bone measurements except lumbar spine in the rheumatoid arthritis group, BMD
      discriminated significantly between the patients with and without vertebral
      deformities, and the results were similar to those obtained in controls. Among
      current corticosteroid users, neither QUS nor DXA could discriminate between
      subjects with and without vertebral deformities. CONCLUSIONS: These findings
      support QUS as an alternative tool for identifying patients at risk of having
      vertebral deformities in rheumatoid arthritis, although results should be
      interpreted with caution in current users of corticosteroids.

PMID- 15249322
TI  - Miscarriage but not fecundity is associated with progression of joint destruction
      in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether reproductive history before disease onset is
      associated with severity of joint destruction in rheumatoid arthritis. METHODS: A
      special early arthritis clinic (EAC) was established at the department of
      rheumatology of Leiden University Medical Centre. General practitioners were
      encouraged to refer patients with joint complaints to this clinic, where the
      diagnosis of rheumatoid arthritis was made by a rheumatologist. In all, 113
      female patients with definite rheumatoid arthritis were included in this study. A
      structured questionnaire was administered and joint damage was assessed by
      sequential x rays of the hands and feet, using the modified Sharp score. RESULTS:
      The length of time of unprotected intercourse until first pregnancy (fecundity)
      was comparable with data from earlier studies, with 16% of the patients reporting
      a time to first pregnancy of more than 12 months. Fecundity did not reflect the
      extent of joint damage over time. The miscarriage rate was 15% per pregnancy,
      comparable to population figures (12-15%). A significant increase in joint damage
      over a two year follow up was found in patients with rheumatoid arthritis who had
      experienced at least one miscarriage compared with those who had never had a
      miscarriage (mean modified Sharp scores at 2 years, 24 (95% confidence interval,
      15 to 32) and 16 (10 to 23), respectively; p<0.05). At baseline, the Sharp scores
      were similar in the two subgroups. CONCLUSIONS: Miscarriage before disease onset
      but not fecundity is associated with the progression of joint damage in
      rheumatoid arthritis.

PMID- 15249323
TI  - Renal clearance and daily excretion of cortisol and adrenal androgens in patients
      with rheumatoid arthritis and systemic lupus erythematosus.
AB  - BACKGROUND: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE),
      patients demonstrate low levels of adrenal hormones. OBJECTIVE: To investigate
      whether increased renal clearance and daily excretion contribute to this
      phenomenon. METHODS: Thirty patients with RA, 32 with SLE, and 54 healthy
      subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17
      hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and
      DHEA sulphate (DHEAS) were measured. RESULTS: Clearance of DHEAS and DHEA was
      lower in patients than in HS, and clearance of androstenedione was somewhat
      higher in patients than in HS, but daily excretion of this latter hormone was
      low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups.
      The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was
      lower in patients than HS (but similar for cortisol). Serum DHEAS levels
      correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10
      times more of this hormone than excreted by patients. Low serum levels of adrenal
      androgens and cortisol in patients as compared with HS were confirmed, and
      proteinuria was not associated with changes of measured renal parameters.
      CONCLUSIONS: This study in patients with RA and SLE demonstrates that low serum
      levels of adrenal androgens and cortisol are not due to increased renal clearance
      and daily loss of these hormones. Decreased adrenal production or increased
      conversion or conjugation to downstream hormones are the most likely causes of
      inadequately low serum levels of adrenal hormones in RA and SLE.

PMID- 15249324
TI  - Relative risk of knee chondrocalcinosis in siblings of index cases with
      pyrophosphate arthropathy.
AB  - OBJECTIVES: To examine the genetic contribution to common, apparently sporadic,
      radiographic knee chondrocalcinosis (CC) and pyrophosphate arthropathy (PA).
      METHOD: (1). DESIGN: radiographic sibling study. Comparison of the prevalences of
      knee CC and PA in siblings of index cases with PA with those in the community.
      (2). SUBJECTS: 80 index cases with PA listed for total knee replacement; 122 of
      their siblings aged >or=40 years; and 1729 participants from community knee pain
      surveys who had undergone knee radiographs. (3). MAIN OUTCOME MEASURE: odds
      ratios of knee CC and PA in siblings versus community participants. RESULTS: The
      prevalence of knee CC was 13% (15/116) in the siblings and 6.9% (119/1727) in the
      community participants. The adjusted odds ratio (aOR) was 1.2, 95% confidence
      interval (CI) 0.6 to 2.3. The main risk factors for knee CC were age, knee pain,
      and knee OA. The prevalence of knee PA was 7% (9/122) in the siblings and 3.4%
      (59/1729) among the community participants (aOR = 1.1, 95% CI 0.4 to 2.7). The
      main risk factors for PA were age and knee pain. The age, sex, and knee pain
      standardised prevalence of PA in the Nottingham community aged >or=40 was 2.40%.
      CONCLUSION: The risk of knee CC and PA in siblings of index cases with PA is no
      higher than that in the general population. Although rare familial CC is
      recognised, this study suggests that no major genetic predisposition to CC occurs
      in common symptomatic knee OA.

PMID- 15249325
TI  - Autologous stem cell transplantation in the treatment of systemic sclerosis:
      report from the EBMT/EULAR Registry.
AB  - OBJECTIVE: To analyse the durability of the responses after haematopoietic stem
      cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine
      whether the high transplant related mortality (TRM) improved with experience.
      This EBMT/EULAR report describes the longer outcome of patients originally
      described in addition to newly recruited cases. METHODS: Only patients with SSc,
      treated by HSCT in European phase I-II studies from 1996 up to 2002, with more
      than 6 months of follow up were included. Transplant regimens were according to
      the international consensus statements. Repeated evaluations analysed complete,
      partial, or non-response and the probability of disease progression and survival
      after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients
      aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n =
      30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5
      81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and
      non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial
      partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7)
      months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression
      accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5
      years, progression probability was 48% (95% CI 28 to 68) and the projected
      survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed
      that response in two thirds of the patients after HSCT was durable with an
      acceptable TRM. Based on these results prospective, randomised trials are
      proceeding.

PMID- 15249326
TI  - Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.
AB  - OBJECTIVES: To identify the immunodominant T cell epitopes of the topoisomerase I
      protein in patients with systemic sclerosis (SSc) and control subjects, using
      computational analysis software (TEPITOPE) and T cell proliferation assays.
      METHODS: Six oligopeptides, predicted by TEPITOPE software as potential
      topoisomerase protein epitopes, were used to perform T cell proliferation assays
      in 21 patients with SSc and 15 healthy controls. RESULTS: A positive response to
      at least one of the peptides was seen in 10/21 patients and 7/15 healthy
      controls. Among responders, the proliferative response was limited to a single
      peptide in 6/7 healthy controls, whereas 5/10 patients responded to more than one
      peptide. In responding patients a significant correlation was found between
      disease duration and number of peptides inducing a response (p = 0.007).
      CONCLUSIONS: Several T cell epitopes of the topoisomerase I protein have been
      identified and evidence has been found to suggest epitope spreading in patients
      with SSc.

PMID- 15249327
TI  - Standard reference values for musculoskeletal ultrasonography.
AB  - OBJECTIVES: To determine standard reference values for musculoskeletal
      ultrasonography in healthy adults. METHODS: Ultrasonography was performed on 204
      shoulders, elbows, hands, hips, knees, and feet of 102 healthy volunteers (mean
      age 38.4 years; range 20-60; 54 women) with a linear probe (10-5 MHz; Esaote
      Technos MP). Diameters of tendons, bursae, cartilage, erosions, hypoechoic rims
      around tendons and at joints were measured with regard to established standard
      scans. Mean, minimum, and maximum values, as well as two standard deviations (2
      SD) were determined. Mean values +/-2 SD were defined as standard reference
      values. RESULTS: Hypoechoic rims were normally present in joints and tendon
      sheaths owing to physiological synovial fluid and/or cartilage. Similarly, fluid
      was found in the subdeltoid bursa in 173/204 (85%), at the long biceps tendon in
      56 (27%), in the suprapatellar recess in 158 (77%), in the popliteal bursae in 32
      (16%), and in the retrocalcaneal bursa in 49 (24%). Erosions of >1 mm were seen
      at the humeral head in 47 (23%). Values for important intervals were determined.
      The correlation between two investigators was 0.96 (0.78-0.99). The reliability
      of follow up investigations was 0.83 (0.52-0.99). CONCLUSIONS: Fluid in bursae as
      well as hypoechoic rims within joints and around tendons are common findings in
      healthy people. This study defines standard reference values for musculoskeletal
      ultrasonography to prevent misinterpretation of normal fluid as an anatomical
      abnormality.

PMID- 15249328
TI  - Non-invasive imaging in the diagnosis and management of Takayasu's arteritis.
AB  - OBJECTIVES: Takayasu's arteritis (TA) is a rare disease, in which early diagnosis
      and assessment of treatment efficacy remain a problem. Signs and symptoms may be
      non-specific and conventional blood tests unreliable, with vascular inflammation
      often persisting in the face of a normal acute phase response. The current "gold
      standard" investigation, x ray angiography, is invasive and only identifies late,
      structural changes in vessels. Recently, non-invasive imaging methods have shown
      promise in the assessment of patients with TA. METHODS: The invasive and non
      invasive imaging performed on all patients in the rheumatology department at the
      Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria
      for TA were reviewed. All patients were clinically active at diagnosis and were
      treated with high dose oral prednisolone and additional oral or intravenous
      immunosuppression. RESULTS: Non-invasive imaging methods
      ([(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) and
      magnetic resonance imaging (MRI)) provided important additional information about
      disease activity ([(18)F]FDG-PET) and progression of vessel wall thickening (MRI)
      when compared with x ray angiography. CONCLUSIONS: Non-invasive imaging methods
      provide useful additional information towards the diagnosis and management of TA.
      Such techniques may allow earlier diagnosis and more accurate assessment of
      response to treatment than conventional clinical assessment and/or angiography.
      Non-invasive imaging is likely to be useful in the management of other large
      vessel vasculitides.

PMID- 15249329
TI  - Association between bronchiectasis and smoking in patients with rheumatoid
      arthritis.

PMID- 15249330
TI  - Successful treatment with fenofibrate, a peroxisome proliferator activated
      receptor alpha ligand, for a patient with rheumatoid arthritis.

PMID- 15249331
TI  - Refractory leg infection as an inducer of the catastrophic antiphospholipid
      syndrome.

PMID- 15249332
TI  - Hepatic manifestations of autoimmune rheumatic diseases.

PMID- 15249333
TI  - Interstitial lung disease, a common manifestation of newly diagnosed polymyositis
      and dermatomyositis.

PMID- 15249334
TI  - Comparison of frozen section and touch imprint cytology for evaluation of
      sentinel lymph node metastasis in breast cancer.
AB  - BACKGROUND: Sentinel lymph node metastasis of breast cancer is evaluated by
      frozen section (FS) or touch imprint cytology (TIC). However, which of the two
      methods is superior remains controversial. Here we directly compared the
      sensitivity of these methods prospectively. METHODS: The study included 208 SNs
      harvested from 107 consecutive patients with breast cancer who underwent sentinel
      lymph node biopsy. SNs were serially sectioned at 2-mm intervals, and two
      sections were subjected to intraoperative evaluation of FS with hematoxylin and
      eosin staining. TIC specimens were prepared from all cut surfaces and analyzed by
      Papanicolaou (TIC) and cytokeratin (TIC with immunohistochemistry; TIHC)
      immunohistochemistry. RESULTS: Thirty-five SNs from 27 patients were positive by
      final histopathology. The sensitivity per sentinel lymph node of FS was 89%; it
      was 86% for TIC and 89% for TIHC. Among 173 negative SNs, the results of FS were
      concordant with final histopathology, but TIC and TIHC were positive in 1 and 5
      histopathology-negative SNs, respectively. The sensitivity per patient of FS was
      85%; it was 85% for TIC and 89% for TIHC. Among 80 patients with node-negative
      disease, the results of FS and TIC were concordant with final histopathology,
      whereas TIHC was positive in 3 patients (3.8% were upstaged). A slight
      improvement of sensitivity per patient was achieved by the combination of FS and
      TIC (to 89%) or FS and TIHC (to 93%). CONCLUSIONS: The sensitivity of FS was
      almost equivalent to that of TIC. TIHC had a better sensitivity than FS and TIC,
      but it upstaged a few node-negative patients.

PMID- 15249335
TI  - A prospective analysis of positron emission tomography and conventional imaging
      for detection of stage IV metastatic melanoma in patients undergoing
      metastasectomy.
AB  - BACKGROUND: Positron emission tomography with 2-deoxy-2-[(18)F]fluoro-D-glucose
      (FDG-PET) is available for evaluation of patients with melanoma. This study
      evaluates the potential of FDG-PET to improve on conventional imaging (CI) in
      patients with stage IV melanoma undergoing metastasectomy. METHODS: This was a
      prospective study comparing radiological evaluation of patients who underwent
      metastasectomy for palliation or cure. Patients underwent preoperative evaluation
      by physical examination, CI by computed tomography and/or magnetic resonance
      imaging, and FDG-PET. Independent observers performed three separate analyses of
      CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI).
      Abnormalities were reported as benign or malignant and assessed by pathologic
      analysis or by clinical outcome determined by disease progression detected on
      serial evaluations. RESULTS: Ninety-four lesions were noted in 18 patients who
      underwent preoperative assessment, metastasectomy, and long-term follow up
      (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity
      of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a
      negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of
      79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the
      sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%,
      respectively. CONCLUSIONS: Combined use of FDG-PET and CI may be an accurate
      strategy to identify sites of disease in patients with stage IV melanoma being
      considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed
      to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on
      lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.

PMID- 15249336
TI  - Acute toxicity of high-dose-rate intracavitary brachytherapy with the MammoSite
      applicator in patients with early-stage breast cancer.
AB  - BACKGROUND: Intracavitary brachytherapy with the MammoSite applicator as the sole
      radiation treatment in breast-conserving therapy is an option for women with
      early-stage breast cancer; we evaluated the acute toxicities associated with this
      treatment method. METHODS: Thirty-one patients with 32 stage I or II breast
      carcinomas underwent breast-conserving therapy, which included lumpectomy with
      negative margins, sentinel node biopsy, or axillary dissection, followed by
      brachytherapy with the MammoSite applicator. Acute radiation skin complications
      were graded on the day of radiotherapy completion and at weeks 2, 4, 6, and 12
      after radiation treatment. Cosmesis was graded on the Harvard Scale at all follow
      ups. RESULTS: The median follow-up was 11 months (range, 4-15 months). Twenty
      seven of the 31 patients were treated with the device as the sole method of
      radiotherapy. No acute toxicities occurred during the 5 days of treatment.
      Nineteen patients (68%) had no to mild acute skin reactions, and 25% developed
      bright erythema and patchy moist desquamation. Two patients (7%) developed
      confluent moist desquamation within the first 4 weeks (grade 3); this healed by
      week 12. All skin reactions were localized to the area overlying the balloon.
      Sixteen percent (5 of 32) of all breasts with implants developed infection.
      Cosmesis was good to excellent in 86% of cases. CONCLUSIONS: Most acute skin
      toxicities were mild. Our infection rate was higher than in prior studies that
      used interstitial brachytherapy. Cosmesis was good to excellent in most patients.
      Breast brachytherapy with the MammoSite catheter was well tolerated; further
      investigations of breast brachytherapy with this system are warranted.

PMID- 15249337
TI  - Is it time to change surgical strategy for gastric cancer in the United States?

PMID- 15249338
TI  - Sentinel lymph node biopsy for early stage clinical n0 squamous cell carcinoma of
      the oral cavity.

PMID- 15249339
TI  - A role for FDG-PET in the surgical management of stage IV melanoma.

PMID- 15249340
TI  - MammoSite RTS: the reporting of initial experiences and how to interpret.

PMID- 15249341
TI  - Validation of ex vivo lymphatic mapping in hematoxylin-eosin node-negative
      carcinoma of the colon and rectum.
AB  - BACKGROUND: Substantial evidence supports that detailed analysis of the regional
      lymphatics will identify previously unrecognized micrometastatic disease in
      colorectal cancer. In order to determine whether the sentinel lymph node(s)
      (SLNs) harvested by ex vivo lymphatic mapping in node-negative colorectal cancer
      (CRC) are the most likely node(s) to harbor micrometastatic disease, we examined
      all nodes in CRC specimens in an identical fashion. METHODS: One hundred twenty
      four specimens from patients with colorectal cancer were delivered to pathology
      in the fresh state and underwent ex vivo sentinel lymph node mapping. If negative
      by routine hematoxylin and eosin (H&E) analysis, the SLNs and non-SLNs were
      subjected to further analysis by level section H&E and immunohistochemical (IHC)
      analysis. RESULTS: A mean of 30 nodes were harvested (range, 5-111). Fifty-one
      patients (41%) were found to be node-positive by routine H&E analysis. SLNs were
      identified in all but three specimens. A total of 2177 nodes were analyzed from
      the 66 H&E node-negative specimens (1883 non-SLNs and 294 SLNs). Overall,
      metastases were identified in 13 of 278 SLNs and in only 5 of 1829 non-SLNs (P
      <.001). Only 5 of 66 patients (7.5%) had evidence of metastatic disease in non
      SLNs when the SLNs were negative. Thirteen apparently node-negative patients
      (19.3%) were upstaged by IHC analysis of the SLNs (P =.04). CONCLUSIONS: If the
      SLN is negative by both H&E and IHC analysis, the probability of finding
      metastases in a non-SLN is remote. If microstaging is demonstrated to be
      prognostically relevant, focused examination should be of the SLN(s).

PMID- 15249342
TI  - Determinants of patients' choice of reconstruction with mastectomy for primary
      breast cancer.
AB  - BACKGROUND: The aim of the study was to measure women's decisions about breast
      reconstruction (BR) after mastectomy and to assess the factors contributing to
      their decisions, in a context involving shared decision-making and maximum
      patient autonomy. METHODS: Women who were about to undergo mastectomy for primary
      breast cancer were systematically offered choices concerning BR and time of
      reconstruction (intervention always covered by the French National Insurance
      System). Self-administered questionnaires were used prior to the operation.
      RESULTS: Among the 181 respondents, 81% opted for BR and 19% for mastectomy
      alone. In comparison with those who chose mastectomy alone, those opting for BR
      more frequently recognized the importance of discussing these matters with the
      surgeon and their partner (adjusted odds ratio [OR(adj)] = 13.45 and 3.59,
      respectively; P <.05) and realized that their body image was important (OR(adj) =
      10.55, P <.01); fears about surgery prevented some of the women from opting for
      BR (OR(adj) = 0.688, P <.05). Among the women opting for BR, 83% chose immediate
      breast reconstruction (IBR) and 17% chose delayed breast reconstruction (DBR).
      The preference for IBR was mainly attributable to the fact that these women had
      benefited more frequently from doctor-patient discussions (OR(adj) = 3.49, P
      <.05) but was also attributable to the patients' physical and functional
      characteristics: they were in a poorer state of health (P <.05). The surgeons
      predicted their patients' preferences fairly accurately. CONCLUSIONS: In a
      context of maximum autonomy, the great majority of the women chose IBR. The
      patients' choices were explained mainly by their psychosocial characteristics.
      The indication for BR should be properly discussed between patients and surgeons
      before mastectomy.

PMID- 15249343
TI  - Closing the circle between minority inclusion in research and health disparities.

PMID- 15249344
TI  - Words that harm, words that heal.

PMID- 15249345
TI  - The fear of beta-blocker therapy in heart failure: time to forget.

PMID- 15249346
TI  - Update in renal transplantation.
AB  - Renal transplantation is the treatment of choice for most patients with end-stage
      renal disease. The shortage of donor organs, however, remains a major obstacle to
      successful, early transplantation. This shortage has actually worsened despite an
      increase in living family-related and unrelated donors. On the other hand, over
      the last 10 years, allograft and recipient survival have significantly improved.
      This encouraging outcome reflects many factors, particularly a favorable shift in
      the balance between the efficacy and toxicity of immunosuppressive regimens. As
      acute rejection and early graft loss have become less common, the focus is
      increasingly directed toward the prevention and treatment of the long-term
      complications of renal transplantation. These include suboptimal allograft
      function, premature death, cardiovascular disease, and bone disease. Thus, a
      multidisciplinary approach--rather than management of immunological issues alone-
      is now required to optimize long-term outcomes of renal transplant recipients.

PMID- 15249347
TI  - Adverse effects of beta-blocker therapy for patients with heart failure: a
      quantitative overview of randomized trials.
AB  - BACKGROUND: Beta-blockers substantially improve survival in patients with chronic
      heart failure (HF) with left ventricular systolic dysfunction, but concerns about
      cardiovascular adverse effects may deter physicians from prescribing this
      therapy. We performed an overview of randomized beta-blocker trials in patients
      with HF to quantify the risks of these adverse effects. METHODS: Heart failure
      trials of beta-blockers were identified by electronic searches of the MEDLINE
      database from 1966 to 2002. The random-effects model was used to combine results
      from individual trials and calculate estimates of risks associated with therapy.
      RESULTS: beta-Blocker therapy was associated with significant absolute annual
      increases in risks of hypotension (11 per 1000; 95% confidence interval [CI], 0
      22), dizziness (57 per 1000; 95% CI, 11-104), and bradycardia (38 per 1000; 95%
      CI, 21-54). There was no significant absolute risk of fatigue associated with
      therapy (3 per 1000; 95% CI, -2 to 9). beta-Blocker therapy was associated with a
      reduction in all-cause withdrawal of medication (14 per 1000; 95% CI, -2 to 29)
      as well as significant reductions in all-cause mortality (34 per 1000; 95% CI, 20
      49), HF hospitalizations (40 per 1000; 95% CI, 22-58), and worsening HF (52 per
      1000; 95% CI, 10-94). CONCLUSIONS: Although beta-blocker therapy was associated
      with hypotension, dizziness, and bradycardia, the absolute increases in risk were
      small, and overall fewer patients were withdrawn from beta-blocker therapy than
      from placebo. This information should alleviate concerns about prescribing this
      life-saving therapy to patients with HF.

PMID- 15249348
TI  - Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes
      mellitus: a meta-analysis.
AB  - BACKGROUND: Obesity is closely related to type 2 diabetes mellitus, and weight
      reduction is an important part of the care delivered to obese persons with
      diabetes. The objective of this review was to assess the efficacy of
      pharmacotherapy for weight loss in adults with type 2 diabetes. METHODS: A
      systematic review of the literature was performed, and studies were included if
      pharmacotherapy was used as the primary strategy for weight loss among adults
      with type 2 diabetes. Published and unpublished studies with any design were
      included. A random effects model was used to combine outcomes from randomized
      controlled trials. RESULTS: Sufficient data for the meta-analysis were available
      for fluoxetine, orlistat, and sibutramine. Fourteen randomized, placebo
      controlled trials were included in the review, with a total of 2231 patients.
      Pharmacotherapy produced modest reductions in weight for fluoxetine (3.4 kg [95%
      confidence interval (CI), 1.7-5.2 kg] at 8-16 weeks of follow-up; 5.1 kg [95% CI,
      3.3-6.9 kg] at 24-30 weeks; and 5.8 kg [ 95% CI, 0.8-10.8 kg] at 52 weeks);
      orlistat (2.6 kg [95% CI, 2.1-3.2 kg] [2.6% loss] at 52 weeks); and sibutramine
      (4.5 kg [95% CI, 1.8-7.2 kg] [3.3% loss] at up to 26 weeks). Glycated hemoglobin
      was also modestly reduced: fluoxetine (1.0% [95% CI, 0.4%-1.5%] at 8-16 weeks;
      1.0% [95% 0.6%-1.4%] at 24-30 weeks; and 1.8% [95% CI, -0.2%-3.8%] at 52 weeks);
      orlistat (0.4% [95% CI, 0.3%-0.5%]); and sibutramine (0.7% [95% CI, -0.5%-1.9%]).
      Gastrointestinal adverse effects were common with orlistat; tremor, somnolence,
      and sweating with fluoxetine; and palpitations with sibutramine. CONCLUSIONS:
      Fluoxetine, orlistat, and sibutramine can achieve statistically significant
      weight loss over 26 to 52 weeks. However, the magnitude of weight loss was
      modest, and the long-term health benefits and safety remain unclear.
      Interventions that combine pharmacologic therapy with intensive behavioral
      interventions may be more effective but need additional research.

PMID- 15249349
TI  - Management of alcohol withdrawal delirium. An evidence-based practice guideline.
AB  - BACKGROUND: Alcohol withdrawal delirium is the most serious manifestation of
      alcohol withdrawal. Evidence suggests that appropriate care improves mortality,
      but systematic reviews are unavailable. METHODS: Articles with original data on
      management of alcohol withdrawal delirium underwent structured review and meta
      analysis. RESULTS: Meta-analysis of 9 prospective controlled trials demonstrated
      that sedative-hypnotic agents are more effective than neuroleptic agents in
      reducing duration of delirium and mortality, with a relative risk of death when
      using neuroleptic agents of 6.6. Statistically significant differences among
      various benzodiazepines and barbiturates were not found. No deaths were reported
      in 217 patients from trials using benzodiazepines or barbiturates. CONCLUSIONS:
      Control of agitation should be achieved using parenteral rapid-acting sedative
      hypnotic agents that are cross-tolerant with alcohol. Adequate doses should be
      used to maintain light somnolence for the duration of delirium. Coupled with
      comprehensive supportive medical care, this approach is highly effective in
      preventing morbidity and mortality.

PMID- 15249350
TI  - Obesity and unhealthy life-years in adult Finns: an empirical approach.
AB  - BACKGROUND: Obesity is more strongly related to morbidity and disability than to
      mortality. Obese individuals are thus expected to have more unhealthy life-years
      than normal-weight persons. The objective of the present study was to quantify
      the number of excess unhealthy life-years in obese individuals. METHODS: A
      representative cohort of 19 518 Finnish men and women aged 20 to 92 years was
      followed for 15 years. Participation rate was 83%. Obesity was defined as a body
      mass index of 30.0 or higher. The number of unhealthy life-years due to premature
      work disability, hospitalization for coronary heart disease, and need for long
      term medication was calculated per category of body mass index. RESULTS: During
      the follow-up of 15 years, obese men who never smoked aged 20 to 64 years had, on
      average, 0.63 more years of work disability, 0.36 more years of coronary heart
      disease, and 1.68 more years of longterm medication use, than normal-weight
      counterparts. Obese women had, respectively, 0.52, 0.46, and 1.49 more years from
      these conditions than normal weight women. The excess risks of morbidity and
      disability due to obesity were highest in the youngest age groups and exceeded
      those of mortality in all age groups. Obese men and women 65 years and older who
      never smoked had, respectively, 1.71 and 1.41 excess unhealthy life-years (not
      statistically significant) due to premature need for long-term medication
      compared with normal-weight subjects, but no excess unhealthy life-years due to
      coronary heart disease. CONCLUSIONS: Obesity has a lifetime impact on disability
      and morbidity. A further increase in obesity will lead to an increase in
      unhealthy life-years and in direct and indirect health care costs.

PMID- 15249351
TI  - The independent effect of type 2 diabetes mellitus on ischemic heart disease,
      stroke, and death: a population-based study of 13,000 men and women with 20 years
      of follow-up.
AB  - BACKGROUND: Epidemiological studies have reported that patients with type 2
      diabetes mellitus (DM) have increased mortality and morbidity from cardiovascular
      diseases, independent of other risk factors. However, most of these studies have
      been performed in selected patient groups. The purpose of the present study was
      prospectively to assess the impact of type 2 DM on cardiovascular morbidity and
      mortality in an unselected population. METHODS: A total of 13,105 subjects from
      the Copenhagen City Heart Study were followed up prospectively for 20 years.
      Adjusted relative risks of first, incident, admission for, or death from ischemic
      heart disease, acute myocardial infarction, or stroke, as well as total mortality
      in persons with type 2 DM compared with healthy controls, were estimated.
      RESULTS: The relative risk of first, incident, and admission for myocardial
      infarction was increased 1.5- to 4.5-fold in women and 1.5- to 2-fold in men,
      with a significant difference between sexes. The relative risk of first,
      incident, and admission for stroke was increased 2- to 6.5-fold in women and 1.5-
      to 2-fold in men, with a significant difference between sexes. In both women and
      men the relative risk of death was increased 1.5 to 2 times. CONCLUSIONS: In
      persons with type 2 DM, the risk of having an incident myocardial infarction or
      stroke is increased 2- to 3-fold and the risk of death is increased 2-fold,
      independent of other known risk factors for cardiovascular diseases.

PMID- 15249352
TI  - Effectiveness of statin therapy in adults with coronary heart disease.
AB  - BACKGROUND: We conducted a meta-analysis of patients with coronary heart disease
      (CHD) to determine the effectiveness of statin therapy; whether effectiveness
      varied according to patient characteristics, outcomes, or pretreatment low
      density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and
      the level at which to initiate statin therapy. METHODS: Randomized trials or
      systematic reviews for secondary prevention of CHD with statin therapy published
      between January 1966 and December 2002 were identified through MEDLINE and the
      Cochrane Library. Studies were included if they randomly assigned adults with CHD
      to statin therapy or control, enrolled at least 100 individuals per arm, reported
      clinical outcomes and LDL-C levels, and were published as full studies in
      English. Two reviewers abstracted data using a prospectively designed protocol.
      RESULTS: Twenty-five studies enrolling 69 511 individuals were included.
      Participants in 19 placebo-controlled trials had a mean age of 63 years and a
      mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin
      therapy reduced CHD mortality or nonfatal myocardial infarction 25% (relative
      risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality
      16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71
      0.83). Beneficial effects were seen in women and the elderly. There were no data
      to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59
      mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L). Meta
      regression analyses revealed risk reductions for CHD mortality or nonfatal
      myocardial infarction and major vascular events across available pretreatment LDL
      C levels. CONCLUSION: Statin therapy reduces mortality and morbidity in adults
      with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L).

PMID- 15249353
TI  - Impact of diabetes and previous myocardial infarction on long-term survival: 25
      year mortality follow-up of primary screenees of the Multiple Risk Factor
      Intervention Trial.
AB  - BACKGROUND: The magnitude of coronary mortality risk associated with diabetes or
      prior myocardial infarction (MI) is debatable. Modulating effects of age, risk
      factors, and duration of follow-up may explain discrepancies in previous
      research. Associations with noncardiovascular mortality are little explored.
      OBJECTIVES: To compare mortality patterns in men with a history of diabetes or MI
      and to assess modulating effects on mortality of age, cardiovascular risk
      factors, and follow-up duration. METHODS: We compared the 25-year mortality of
      4809 men with diabetes only and 4625 men with MI only (all men aged 35-57 years).
      RESULTS: The adjusted hazard ratio (HR) for all-cause mortality for those with MI
      only vs those with diabetes only was 0.97 (95% confidence interval, 0.92-1.03; P
      =.32). The pattern of deaths was different: higher coronary mortality (HR = 1.37;
      P<.001) and lower mortality from noncardiovascular causes (HR = 0.66; P<.001) in
      those with MI only compared with those with diabetes only. This finding prevailed
      across all ages and levels of cardiovascular risk factors. Hazard ratios for
      coronary mortality significantly declined over follow-up (2.7, 1.7, 1.2, 1.1, and
      1.0 for < or =5, 6-10, 11-15, 16-20, and >20 years of follow-up, respectively),
      whereas HRs for noncardiovascular mortality remained relatively constant.
      CONCLUSIONS: Overall, diabetes and MI were similarly strong predictors of total
      mortality. Higher mortality from noncardiovascular causes was observed in those
      with diabetes only, whereas prior MI was more strongly predictive of coronary
      mortality than diabetes at any age and level of cardiovascular risk factors. The
      difference in coronary mortality between the 2 groups was most evident in the
      first 10 years of follow-up.

PMID- 15249354
TI  - A probabilistic model for predicting hypoglycemia in type 2 diabetes mellitus:
      The Diabetes Outcomes in Veterans Study (DOVES).
AB  - BACKGROUND: To develop and validate a method for estimating hypoglycemia risk in
      stable, insulin-treated subjects with type 2 diabetes mellitus. METHODS: Subjects
      (n = 195) monitored their blood glucose levels 4 times daily for 8 weeks. An 8
      week mean blood glucose value (GLUMEAN) with standard deviation (GLUSD) was
      derived for each patient. Subjects were then randomly allocated to a derivation
      or validation set. For the derivation set, we developed a logistic function based
      on GLUMEAN and GLUSD to describe the 8-week risk of hypoglycemia (blood glucose <
      or =60 mg/dL [3.3 mmol/L]). This function was used to assign a predicted
      probability of hypoglycemia to each subject in the validation set. Subjects were
      assigned to risk quartiles and followed up for up to 52 weeks. RESULTS: We
      evaluated 195 subjects, 95% of whom were men and 69% of whom were non-Hispanic
      white. For 72 derivation subjects, GLUMEAN and GLUSD were highly influential
      determinants of hypoglycemia during intensified monitoring. The 123 validation
      subjects were followed up for 39.7 +/- 7.1 weeks (mean +/- SD). The occurrence of
      long-term hypoglycemia differed significantly across risk quartiles (19.4%,
      36.7%, 61.3%, and 77.4%, respectively; P<.001). Receiver operating characteristic
      curve analysis showed that the area for the probability function (0.746 +/-
      0.046) was significantly higher than the area for hemoglobin A1c (0.549 +/-
      0.052) because their 95% confidence intervals did not overlap. The function also
      identified subjects who developed long-term hypoglycemia at a rate exceeding the
      median frequency. CONCLUSIONS: Self-monitoring of blood glucose is superior to
      hemoglobin A1c measurement in predicting long-term hypoglycemia in persons with
      type 2 diabetes. The risk of hypoglycemia associated with treatment
      intensification may be offset by strategies that reduce glucose variability.

PMID- 15249355
TI  - A survey of knowledge, attitudes, and beliefs of house staff physicians from
      various specialties concerning antimicrobial use and resistance.
AB  - BACKGROUND: Examination of knowledge, attitudes, and beliefs of house staff
      physicians will be important in developing interventions to improve antimicrobial
      use and prevent resistance. METHODS: A 75-item survey was distributed to house
      staff physicians on nonpediatric services in a university teaching hospital.
      Knowledge was assessed with a 10-question quiz. RESULTS: The survey was completed
      by 179 (67%) of 269 house staff physicians on 5 specialties. Outside and inside
      the intensive care unit, 21% and 25% of respondents, respectively, reported that
      they were using antibiotics optimally. Surgeons were significantly more likely
      than other physicians to report that they were regularly seeking input into
      antimicrobial selections (P<.001). Of the 170 physicians who completed the
      survey, 88% agreed antibiotics are overused in general and 72% also agreed this
      was the case at their institution (r = 0.56; P<.05); 96% agreed that hospitals in
      general face serious problems with antibiotic resistance and 93% agreed that
      their hospital faces these same problems (r = 0.57; P<.05); 97% agreed that
      better use of antibiotics would reduce resistance; 32% stated that they had not
      had formal teaching on antimicrobial agents in the last year (medicine residents
      reported significantly more formal teaching than others [P =.001]); and 90%
      wanted more education about antimicrobials and 67% wanted more feedback on
      antimicrobial selections. The mean antimicrobial quiz score was 28%, with
      medicine residents scoring significantly higher than others (P =.04). Upper-level
      residents did not perform better than interns. CONCLUSIONS: This survey (1)
      revealed that house staff are aware of the importance of antimicrobial resistance
      and believe better antimicrobial use will help this problem and (2) demonstrated
      differences between specialties with respect to antimicrobial use and knowledge.
      House staff at our hospital have suboptimal knowledge about antimicrobials, and
      this knowledge did not increase appreciably over the course of their training.
      Antimicrobial education is needed and is likely to be well received by house
      staff physicians in academic centers but may be more effective if it is tailored
      to specific specialties.

PMID- 15249356
TI  - Implications of diabetes in patients with acute coronary syndromes. The Global
      Registry of Acute Coronary Events.
AB  - BACKGROUND: There are limited data describing the presenting characteristics,
      management, and outcomes of diabetic and nondiabetic patients with an acute
      coronary syndrome (ACS). OBJECTIVE: To examine differences in these factors,
      patients with ST-segment elevation acute myocardial infarction, non-ST-segment
      elevation acute myocardial infarction, and unstable angina were enrolled in a
      large multinational coronary disease registry. METHODS: The Global Registry of
      Acute Coronary Events is a prospective observational study of patients
      hospitalized with an ACS at 94 hospitals in 14 countries. The study sample
      consisted of 5403 patients with ST-segment elevation acute myocardial infarction,
      4725 with non-ST-segment elevation acute myocardial infarction, and 5988 with
      unstable angina. RESULTS: Approximately 1 in 4 patients presented to
      participating hospitals with a history of diabetes. Patients with diabetes were
      older, more often women, with a greater prevalence of comorbidities, and they
      were less likely to be treated with effective cardiac therapies than nondiabetic
      patients. Patients with diabetes who developed an ACS were at increased risk for
      each hospital outcome examined including heart failure, renal failure,
      cardiogenic shock, and death. These differences remained after adjustment for
      potentially confounding prognostic factors. CONCLUSIONS: A considerable
      proportion of patients with an ACS has diabetes and is at increased risk for
      adverse outcomes compared with patients without diabetes. There are certain
      proven therapeutic strategies that remain underused in the diabetic population. A
      more widespread awareness of this increased risk and a more diligent use of
      proven cardiac treatment approaches are indicated for patients with diabetes who
      develop an ACS.

PMID- 15249357
TI  - Infective endocarditis, cardiac tamponade, and AIDS as serious complications of
      acupuncture.

PMID- 15249359
TI  - Corneal changes after small-incision cataract surgery in patients with diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate functional impairment in the corneal endothelium of eyes
      in patients with diabetes mellitus, after small-incision cataract surgery.
      METHODS: Evaluation was performed in 93 eyes in patients with type 2 diabetes
      mellitus (diabetic group) and 93 eyes in patients without diabetic mellitus
      (nondiabetic group) who underwent cataract surgery. Using a topography system,
      the corneal thickness in the central area was measured before surgery and 1 day,
      1 week, and 1 month after surgery. Corneal endothelial cells were counted using a
      noncontact specular microscope. RESULTS: No significant differences in any
      preoperative measures were observed between the diabetic and nondiabetic groups.
      The increase in corneal thickness 1 month after surgery was significantly higher
      in the diabetic group than in the nondiabetic group (P =.03). The corneal
      endothelial cell losses 1 day and 1 week after surgery were significantly higher
      in the diabetic group than in the nondiabetic group (after 1 day, P =.03; and
      after 1 week, P =.04). CONCLUSION: Compared with nondiabetic eyes, eyes of
      patients with diabetes mellitus showed more damage in corneal endothelial cells
      due to cataract surgery and a delay in the postoperative recovery of corneal
      edema.

PMID- 15249358
TI  - A 5-year, multicenter, open-label, safety study of adjunctive latanoprost therapy
      for glaucoma.
AB  - OBJECTIVE: To evaluate the 5-year safety and efficacy of adjunctive 0.005%
      latanoprost once daily. METHODS: Patients with primary open-angle or exfoliation
      glaucoma who completed a 3-year, open-label, uncontrolled, prospective trial
      could enter a 2-year extension phase. High-resolution color photographs of irides
      were taken at baseline and at 14 subsequent visits. Photographs were assessed for
      change in iris pigmentation compared with baseline. Intraocular pressures and
      adverse events were recorded. MAIN OUTCOME MEASURE: Development and progression
      of increased iris pigmentation over 5 years. RESULTS: Of the 519 original
      patients, 380 enrolled in the extension phase with approximately 89% having an
      eye color known to be susceptible to color change. After 5 years, most patients
      had no increase in iris pigmentation, but certain colored irides exhibited
      notably greater susceptibility than others. For those whose irides did change,
      onset occurred during the first 8 months in 74% and during the first 24 months in
      94%. No patient developed an increase in pigmentation after month 36; the rate of
      progression decreased over time. Adverse event profiles were similar for patients
      with and without increased pigmentation. The overall mean intraocular pressure
      reduction from baseline of 25% was sustained with no need for change in
      intraocular pressure-lowering treatment in 70% of the eyes. CONCLUSION:
      Latanoprost therapy is safe and well tolerated for long-term treatment of open
      angle glaucoma.

PMID- 15249360
TI  - Multifocal electroretinographic evaluation of long-term hydroxychloroquine users.
AB  - OBJECTIVES: To observe the long-term effects of hydroxychloroquine sulfate on
      retinal electrical activity by multifocal electroretinography (mfERG) and to
      evaluate the regional variation of retinal dysfunction in subjects with
      hydroxychloroquine retinopathy. METHODS: Multifocal ERG with 103-hexagon
      stimulation was performed on 19 patients (36 eyes) treated with
      hydroxychloroquine for systemic lupus erythematosus, rheumatoid arthritis, or
      localized atypical scleroderma. Visual acuity testing, Amsler grid testing, and
      Ishihara color vision testing were also performed. In 2 of the patients,
      hydroxychloroquine was discontinued due to concerns about toxicity. Both of these
      patients had additional mfERG performed after discontinuation of medication.
      RESULTS: Twelve patients (19 eyes) had a normal response density in one or both
      eyes, including 6 patients (12 eyes) with a low lifetime dose (< or =438 g) of
      hydroxychloroquine who had normal response densities in both eyes. Eleven
      patients (17 eyes) had abnormal response densities in one or both eyes, and 2 of
      these patients (4 eyes) had significant attenuation of response densities in
      almost the whole tested field; 4 patients had a normal mfERG result for one eye
      but had a slight decrease of response densities for the other eye. There were 4
      patterns of abnormal mfERG amplitude change observed: (1) paracentral loss, (2)
      foveal loss, (3) peripheral loss, and (4) generalized loss. Implicit times were
      abnormal for pericentral responses in 3 patients. The results of color vision and
      Amsler grid testing were normal, except for one patient with a generalized loss
      pattern. In 2 subjects in whom hydroxychloroquine toxicity was suspected,
      response densities improved after termination of hydroxychloroquine. CONCLUSIONS:
      Long-term hydroxychloroquine use may be associated with mfERG abnormalities. The
      mfERG appears to detect retinal physiological change earlier than visual acuity
      testing, color vision testing, or Amsler grid testing can. The greatest value of
      the mfERG is in differentiating a retinal cause and, hence, providing important
      evidence for hydroxychloroquine toxicity, for whatever visual field loss is
      apparent on perimetry.

PMID- 15249361
TI  - Use of an arginine-restricted diet to slow progression of visual loss in patients
      with gyrate atrophy.
AB  - OBJECTIVE: To quantify the effect of long-term reduction of plasma ornithine
      levels through adherence to an arginine-restricted diet on visual function in
      patients of all ages with gyrate atrophy of the retina and choroid. METHODS: A
      long-term observational study was conducted on 27 patients with gyrate atrophy,
      17 of whom elected to comply with the arginine-restricted diet and 10 who were
      unable to comply. The mean rates of change in the electroretinogram combined
      response, electroretinogram flicker response, and kinetic and static perimetry
      were determined. RESULTS: After mean follow-up of 13.9 years for the patients on
      the diet and 14.1 years for those not on the diet, the mean rates of change for
      the diet group compared with those of the no-diet group were statistically
      significantly slower for all outcome measures (age-adjusted P<.05) except for
      static perimetry (P =.06). CONCLUSIONS: Adhering to an arginine-restricted diet
      so as to lower the plasma ornithine level below an average of 5.29 to 6.61 mg/dL
      (400-500 micromol/L) will slow the loss of function as measured by sequential
      electroretinography and visual field examinations.

PMID- 15249362
TI  - Effect of laser photocoagulation on the retinal vessel diameter in branch and
      macular vein occlusion.
AB  - OBJECTIVE: To investigate the response of retinal vessel diameters to
      photocoagulation treatment and their role for the success of laser treatment in
      patients with retinal vein occlusion. METHODS: The study included 14 patients
      with branch vein occlusion or macular vein occlusion. The ophthalmologic
      examination included best-corrected visual acuity, biomicroscopy, fundus
      photography, and fluorescein angiography. Retinal vessel diameters were
      quantified before and after laser photocoagulation using a retinal vessel
      analyzer. MAIN OUTCOME MEASURE: Retinal vessel diameters. RESULTS: In cases
      manifesting macular vein occlusions, no significant change of the vessel diameter
      in any vessel was observed during the follow-up period. In the group with branch
      vein occlusion, all vessels tended to constrict after the laser photocoagulation.
      The effect of laser treatment on retinal vessel diameters was significant for
      superotemporal (P =.045, analysis of variance [ANOVA]) and inferotemporal branch
      veins (P =.03, ANOVA). Vasoconstriction was more pronounced in the occluded
      branch veins (P =.009, ANOVA) compared with the nonaffected veins (P =.12;
      ANOVA). The change of visual acuity after 3 months was correlated with the change
      of vessel diameter 3 months after laser treatment for occluded venular branches
      (r = 0.78, P =.02, linear regression). There was no correlation between the
      number of laser burns and the change of vessel diameters in the affected veins in
      this period (r = 0.12, P =.75, linear regression). CONCLUSIONS: Our results show
      that retinal photocoagulation in patients with branch vein occlusion has a
      vasoconstrictive effect on occluded veins. The correlation between the change in
      visual acuity and the change in vessel diameter indicates that branch vein
      constriction after photocoagulation may be an early indicator of the success of
      laser treatment.

PMID- 15249363
TI  - Effect on visual outcome after macular hole surgery when staining the internal
      limiting membrane with indocyanine green dye.
AB  - OBJECTIVES: To determine the effect on the visual outcome after macular hole
      surgery when staining the internal limiting membrane (ILM) with indocyanine green
      (ICG) dye and to study the mechanism of the adverse effects. PATIENTS AND
      METHODS: We studied 40 eyes of 38 patients with an idiopathic macular hole (size,
      <0.5 disc diameter; duration, <12 months). The concentration, exposure time, and
      amount of the ICG solution that was minimally required to make the ILM visible
      were determined. The patients were randomly divided into group 1 (20 eyes of 19
      patients) who underwent ILM peeling without ICG staining, and group 2 (20 eyes of
      19 patients) who underwent ILM peeling with ICG staining. Routine examinations
      were conducted during the 12-month follow-up period. Multifocal
      electroretinogram, optical coherence tomography, and fluorescein angiography were
      performed on 31 eyes of 30 patients. RESULTS: The macular hole was closed in all
      patients. Visual acuity was improved in both groups, but it was significantly
      better in group 1 (median, 0.85) than in group 2 (median, 0.60; P =.02) after 12
      months. The improvement of visual acuity in group 1 (logarithm of the minimum
      angle of resolution [logMAR] units [SD], 0.82 [0.19]) was significantly better
      than that in group 2 (logMAR units, 0.67 [0.21]; P =.30). The multifocal
      electroretinogram and optical coherence tomographic findings were not
      significantly different in the 2 groups. Fluorescein angiogram showed only weak
      hyperfluorescence at the macula in some patients of both groups. CONCLUSIONS: The
      results suggest that ICG staining should not be used as long as the visibility of
      the retinal surface is good. However, ICG staining may be acceptable at a low
      concentration when a clear view of the retinal surface is unattainable. The
      results of the multifocal electroretinogram, optical coherence tomography, and
      fluorescein angiography suggest that the differences in visual recovery were
      caused not only by pigment epithelial cell damage or retinal toxic effect but
      also probably by the effect of ICG staining on ganglion cells and their axons.

PMID- 15249364
TI  - Treatment of epithelial ingrowth after laser in situ keratomileusis with
      mechanical debridement and flap suturing.
AB  - OBJECTIVE: To evaluate the efficacy and safety of mechanical debridement and
      suturing of the laser in situ keratomileusis (LASIK) flap in the treatment of
      clinically significant epithelial ingrowth after LASIK. METHODS: In a
      retrospective study, 20 eyes (n = 19 patients) in which clinically significant
      epithelial ingrowth developed after LASIK were treated with lifting of the flap,
      scraping of the epithelial ingrowth, and flap suturing. Primary outcome
      measurements including recurrence of ingrowth, uncorrected visual acuity (VA),
      manifest refraction, best spectacle-corrected VA, and complications were
      evaluated at the last postoperative examination. RESULTS: At the last
      postoperative examination (mean +/- SD, 10.5 +/- 14.3 months; range, 1.5-64
      months), 100% of eyes had no recurrence of clinically significant epithelial
      ingrowth. The uncorrected VA changed from 20/20 or better in 7 eyes (35%) and
      20/40 or better in 15 eyes (75%) preoperatively to 20/20 or better in 9 eyes
      (45%) and 20/40 or better in 16 eyes (80%) at the last follow-up examination.
      There was no significant change in the mean logarithm of the minimum angle of
      resolution (logMAR) uncorrected VA before (mean +/- SD, 0.3 +/- 0.5; range, -0.1
      to 1.7) and after surgery (mean +/- SD, 0.2 +/- 0.4; range, -0.1 to 1.7) (P
      =.40). Mean +/- SD spherical equivalent changed from -0.21 +/- 0.82 diopters (D)
      (range, -1.25 to 1.00 D) preoperatively to -0.53 +/- 0.89 D (range, -2.50 to 0.38
      D) at last follow-up (P =.30). No eyes lost 2 or more lines of best spectacle
      corrected VA, and there were no complications associated with the treatment.
      CONCLUSIONS: Suturing the LASIK flap in addition to mechanical debridement of
      epithelial ingrowth is a safe and effective treatment for clinically significant
      epithelial ingrowth after LASIK.

PMID- 15249365
TI  - Selective photodynamic therapy by targeted verteporfin delivery to experimental
      choroidal neovascularization mediated by a homing peptide to vascular endothelial
      growth factor receptor-2.
AB  - OBJECTIVE: To evaluate the feasibility, efficacy, and selectivity of photodynamic
      therapy (PDT) using targeted delivery of verteporfin to choroidal
      neovascularization (CNV) in the rat laser-injury model of CNV. METHODS: We
      performed PDT in rat eyes on experimental CNV and normal retina and choroid using
      verteporfin conjugates. A targeted verteporfin conjugate was made by conjugating
      verteporfin (after isolation from its liposomal formulation) to a modified
      polyvinyl alcohol (PVA) polymer (verteporfin-PVA) followed by linkage to the
      peptide ATWLPPR known to bind the receptor for vascular endothelial growth
      factor, VEGFR2. The verteporfin-PVA conjugate served as a control. We performed
      fluorescent fundus angiography to determine the optimal timing of light
      application for PDT using the conjugates. Closure of CNV was assessed
      angiographically and graded in a masked standardized fashion. We used
      standardized histological grading to compare the effects on normal retina and
      choroid. RESULTS: The verteporfin-PVA conjugation ratio was on average 28:1. The
      conjugate retained typical emission/excitation spectra and photosensitizing
      activity and was as efficient as an equivalent amount of verteporfin. Peak
      intensity of targeted verteporfin in CNV was detected angiographically at 1 hour
      after intravenous injection. Photodynamic therapy using targeted verteporfin (3
      or 4.5 mg/m2) with light application 1 hour after drug injection showed
      angiographic closure of all treated CNV (17/17) 1 day after treatment.
      Photodynamic therapy using verteporfin-PVA at the same drug dose achieved closure
      in 18 of 20 CNV. Histological examination after PDT of normal retina and choroid
      using targeted verteporfin and irradiation at 1 hour showed minimal effect on
      retinal pigment epithelium and no injury to photoreceptors, whereas PDT using
      verteporfin-PVA resulted in retinal pigment epithelium necrosis and mild damage
      to photoreceptors. CONCLUSIONS: Verteporfin bound to the targeting peptide,
      ATWLPPR, retained its spectral and photosensitizing properties. Angiography
      demonstrated localization of the targeted verteporfin 1 hour after injection.
      Photodynamic therapy using targeted verteporfin and the control conjugate were
      more effective in causing CNV closure than standard liposomal verteporfin. The
      targeted verteporfin resulted in more selective treatment than the control
      conjugate or standard verteporfin. These results suggest that targeted PDT
      strategies based on selective expression of receptors on CNV vasculature may
      improve current therapy. CLINICAL RELEVANCE: Targeted PDT for CNV is feasible and
      may offer a qualitative improvement in current treatments for patients with age
      related macular degeneration. This study provides the basis for further
      preclinical studies of targeted PDT strategies and subsequent clinical trials.

PMID- 15249366
TI  - Monocyte activation in patients with age-related macular degeneration: a
      biomarker of risk for choroidal neovascularization?
AB  - OBJECTIVE: To evaluate the activation state of macrophage function in patients
      with age-related macular degeneration (AMD) by quantifying the production of the
      proinflammatory and angiogenic factor tumor necrosis factor alpha (TNF-alpha) and
      by correlating its expression with dry and wet AMD. METHODS: Circulating
      monocytes were obtained from the blood of patients with AMD or age-matched
      control subjects by gradient centrifugation. The monocytes were then analyzed for
      either TNF-alpha release from cultured macrophages in response to retinal pigment
      epithelium-derived blebs and cytokines or TNF-alpha messenger RNA content by
      reverse transcriptase-polymerase chain reaction. RESULTS: In human monocytes
      obtained from controls and AMD patients, TNF-alpha was expressed by freshly
      isolated monocytes and produced by macrophages in culture after stimulation with
      retinal pigment epithelium-derived blebs. However, wide variability in TNF-alpha
      expression was observed among different patients. Patients with monocytes that
      expressed the greatest amount of TNF-alpha demonstrated higher prevalence of
      choroidal neovascularization. CONCLUSIONS: Both controls and AMD patients vary in
      the activation state (defined as TNF-alpha expression) of circulating monocytes.
      Partially active monocytes, defined as high TNF-alpha expression, may be a
      biomarker to identify patients at risk for formation of choroidal
      neovascularization. CLINICAL RELEVANCE: Early diagnostic testing may prove useful
      to detect those patients who will progress to the more severe complications of
      the disease.

PMID- 15249367
TI  - Racial variations in causes of vision loss in nursing homes: The Salisbury Eye
      Evaluation in Nursing Home Groups (SEEING) Study.
AB  - OBJECTIVE: To determine the prevalence and causes of low vision in a large sample
      of nursing home residents. METHODS: Twenty-eight nursing homes on the Eastern
      Shore of Maryland and Delaware were enrolled in a clinical trial to assess the
      impact of vision restoration/rehabilitation on nursing home residents. Visual
      acuity was measured using both recognition charts and preferential looking
      techniques. An ophthalmologist examined all residents with visual acuity worse
      than 20/40 in the better-seeing eye and determined the primary cause for
      decreased vision. Results are reported for the better-seeing eye. RESULTS: Of
      2544 eligible residents, 1591 (63%) participated, but 286 residents were unable
      to respond to visual acuity testing. Of the remaining 1307 residents, 496 (37%)
      had best-corrected visual acuity worse than 20/40 in the better-seeing eye.
      Causes were ascribed for 412 subjects. Rates of low vision were similar between
      African American subjects and white subjects (39% and 38%, respectively; age
      adjusted P =.18). Cataract was the leading cause of low vision, responsible for
      37% of low vision among white subjects and 54% of low vision among African
      American subjects. Macular degeneration was responsible for 29% of low vision
      among white subjects but only 7% among African American subjects. Glaucoma caused
      low vision in 4% of white subjects and 10% of African American subjects.
      Refractive error was not a frequent cause of low vision in nursing home
      residents. CONCLUSIONS: Low vision is highly prevalent among nursing home
      residents, with 37% having visual acuity worse than 20/40 in the better-seeing
      eye. Differences in causes of low vision between African American subjects and
      white subjects were noted, with African American subjects more likely to have
      vision loss on the basis of cataract, a readily treated condition. Appropriate
      interventions for nursing home residents, who face significant obstacles in
      accessing eye care services, have the potential to improve the quality of life of
      this at-risk older population.

PMID- 15249369
TI  - Reporting the results of randomized clinical trials: a priority of Archives of
      Ophthalmology.

PMID- 15249368
TI  - The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations.
AB  - OBJECTIVES: To describe the phenotype of Leber congenital amaurosis (LCA) in 26
      probands with mutations in aryl hydrocarbon receptor interacting protein-like 1
      protein (AIPL1) and compare it with phenotypes of other LCA-related genes. To
      describe the electroretinogram (ERG) in heterozygote carriers. METHODS: Patients
      with AIPL1-related LCA were identified in a cohort of 303 patients with LCA by
      polymerase chain reaction single-strand confirmational polymorphism mutation
      screening and/or direct sequencing. Phenotypic characterization included clinical
      and ERG evaluation. Seven heterozygous carrier parents also underwent ERG
      testing. RESULTS: Seventeen homozygotes and 9 compound heterozygotes were
      identified. The W278X mutation was most frequent (48% of alleles). Visual
      acuities ranged from light perception to 20/400. Variable retinal appearances,
      ranging from near normal to varying degrees of chorioretinal atrophy and
      intraretinal pigment migration, were noted. Atrophic and/or pigmentary macular
      changes were present in 16 (80%) of 20 probands. Keratoconus and cataracts were
      identified in 5 (26%) of 19 patients, all of whom were homozygotes. The ERG of a
      parent heterozygote carrier revealed significantly reduced rod function, while
      ERGs for 6 other carrier parents were normal. CONCLUSIONS: The phenotype of LCA
      in patients with AIPL1 mutations is relatively severe, with a maculopathy in most
      patients and keratoconus and cataract in a large subset. Rod ERG abnormalities
      may be present in heterozygous carriers of AIPL1 mutations. CLINICAL RELEVANCE:
      Understanding and recognizing the phenotype of LCA may help in defining the
      course and severity of the disease. Identifying the gene defect is the first step
      in preparation for therapy since molecular diagnosis in LCA will mandate the
      choice of treatment.

PMID- 15249370
TI  - AIDS and ophthalmology in 2004.

PMID- 15249371
TI  - Accelerated drug development through combined phase 2/3 clinical trial design.

PMID- 15249372
TI  - Advantages and potential dangers of presentation before publication: third in a
      series on editorship.

PMID- 15249373
TI  - Fish stories and clinical trials.

PMID- 15249374
TI  - Plotting visual fields using contralateral fixation: a novel honeycomb device.
AB  - A device that maintains steady fixation while plotting the visual field of an eye
      with a large central defect is presented. The device is composed of multiple
      adjacent pinhole tubes mounted on an eye shield and placed in front of the seeing
      fellow eye. The device constricts the visual field of the fixating nontested eye
      to preserve only the central 3 degrees, thus not interfering with the visual
      field of the tested eye. We tested 3 healthy volunteers with simulated visual
      field defects and more than 100 patients with unilateral loss of central vision.
      The use of this device allowed us to plot visual field defects with clear-cut
      borders while no meaningful results could be obtained without it. We found this
      device to be efficient, simple to use, and suitable for all varieties of
      perimetry.

PMID- 15249375
TI  - Microbial keratitis identified during eye bank screen of corneoscleral tissue
      harvested from patients with laser in situ keratomileusis history.

PMID- 15249376
TI  - Pigmented conjunctival lesions as initial manifestation of ochronosis.

PMID- 15249377
TI  - Anterior uveitis and concurrent allergic conjunctivitis associated with long-term
      use of topical 0.2% brimonidine tartrate.

PMID- 15249378
TI  - Optical coherence tomography findings in foveal schisis.

PMID- 15249379
TI  - Bilateral serous retinal detachment due to protein-losing enteropathy.

PMID- 15249380
TI  - Phenotypic variation in ophthalmic manifestations of MIDAS syndrome
      (microphthalmia, dermal aplasia, and sclerocornea).

PMID- 15249381
TI  - A "negative" temporal artery biopsy, positive for arteritis.

PMID- 15249382
TI  - The role of midface lift and lateral canthal repositioning in the management of
      euryblepharon.

PMID- 15249383
TI  - Fundus autofluorescence and vitelliform macular dystrophy.

PMID- 15249384
TI  - Intravitreal injection of triamcinolone for diffuse diabetic macular edema.

PMID- 15249385
TI  - Intravitreal injection of triamcinolone acetonide for diabetic macular edema.

PMID- 15249386
TI  - Safety and efficacy of intravitreal triamcinolone.

PMID- 15249387
TI  - Intravitreal injection of triamcinolone for diffuse diabetic macular edema.

PMID- 15249388
TI  - Intravitreal injection of triamcinolone for diffuse macular edema.

PMID- 15249390
TI  - Ocular hypertension treatment study.

PMID- 15249392
TI  - Endothelial changes associated with topical dorzolamide do appear to be
      significant.

PMID- 15249394
TI  - Is part of the ophthalmologist's role in age-related macular degeneration change
      management of a chronic disease?

PMID- 15249396
TI  - International guidelines: all for one and one for all?

PMID- 15249398
TI  - Idiopathic orbital inflammatory disease.

PMID- 15249400
TI  - Department of Surgery, Duke University Medical Center, Durham, NC.

PMID- 15249402
TI  - Increased acid exposure in patients with gastroesophageal reflux disease
      influences cyclooxygenase-2 gene expression in the squamous epithelium of the
      lower esophagus.
AB  - HYPOTHESIS: Although genetic changes associated with the progression to Barrett
      esophagus and adenocarcinoma have been identified, changes in gene expression
      associated with gastroesophageal reflux disease have not been reported. We
      examined expression levels of several genes important in carcinogenesis and
      compared expression levels with alterations in esophageal acid exposure.
      PATIENTS, DESIGN, AND SETTING: Prospective analysis of 61 patients initially seen
      with reflux symptoms at a private academic hospital. INTERVENTIONS: Paired
      esophageal biopsy specimens of squamous epithelium 3 cm above the squamocolumnar
      junction. All patients had 24-hour pH monitoring performed. MAIN OUTCOME
      MEASURES: Cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase
      reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein
      acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox
      transcription factor 2 (CDX2) messenger RNA expression analysis was performed on
      snap-frozen, microdissected tissue using a quantitative reverse transcriptase
      polymerase chain reaction method. Linear regression and the Pearson product
      moment correlation were used to relate gene expression to parameters of the 24
      hour pH record. RESULTS: Expression levels of COX-2 correlated positively with
      the 24-hour pH score (r = 0.25, P =.05). There was no correlation between the
      expression of other tested genes and esophageal acid exposure. There was also no
      significant increase in COX-2 expression in patients with esophagitis or in those
      who used nonsteroidal anti-inflammatory drugs. CONCLUSIONS: To our knowledge,
      these data provide among the first reported correlation of genetic changes and
      increased esophageal acid exposure in patients with gastroesophageal reflux
      symptoms. The changes in gene expression occur before any metaplastic changes in
      the tissue are apparent, and may in the future be useful in predicting which
      patients will progress through a metaplasia-dysplasia carcinoma sequence.

PMID- 15249403
TI  - Pancreaticoduodenectomy: a 20-year experience in 516 patients.
AB  - HYPOTHESIS: Pancreaticoduodenectomy (PD) is a safe procedure for a variety of
      periampullary conditions. DESIGN: Retrospective review of a prospectively
      collected database. SETTING: Academic tertiary care hospital. PATIENTS: A total
      of 516 consecutive patients who underwent PD. MAIN OUTCOME MEASURES: Patient
      outcomes and survival factors. RESULTS: Pathological examination demonstrated 57%
      periampullary cancers, 22% chronic pancreatitis, 12% cystic neoplasms, 4% islet
      cell neoplasms, and 5% other. Fifty-one percent of patients underwent pylorus
      preservation. Median operating time was 5 hours; blood loss, 1300 mL; and
      transfusion requirement, 1.5 U. Postoperative complications occurred in 43% of
      patients, including cardiopulmonary events (15%), fistula (9%), delayed gastric
      emptying (7%), and sepsis (6%). Additional surgery was required in 3% of
      patients, most commonly because of bleeding. Perioperative mortality was 3.9%
      overall but only 1.8% in patients with chronic pancreatitis; 25% of patients who
      died had preoperative complications associated with their periampullary
      condition. Three-year survival was 15% after resection for pancreatic cancer, 42%
      for duodenal cancer, 53% for ampullary cancer, and 62% for bile duct cancer.
      Univariate predictors of long-term survival in patients with periampullary
      adenocarcinoma included elevated glucose levels, liver function test results,
      abnormal tumor markers, blood loss, transfusion requirement, type of operation,
      and pathologic findings (periampullary adenocarcinoma type, differentiation, and
      margin and node status). Multivariate predictors were serum total bilirubin
      level, blood loss, operation type, diagnosis, and lymph node status. CONCLUSIONS:
      Pancreaticoduodenectomy continues to be associated with considerable morbidity.
      With careful patient selection, PD can be performed safely. Long-term survival in
      patients with periampullary adenocarcinoma can be predicted by preoperative
      laboratory values, intraoperative factors, and pathologic findings.

PMID- 15249404
TI  - Angiographic embolization for pelvic fractures in older patients.
AB  - HYPOTHESIS: Old age predicts reliably the presence of pelvic bleeding, requiring
      angiographic embolization (AE) among blunt trauma patients with major pelvic
      fractures. DESIGN: Four-year prospective observational study (April 1, 1999, to
      May 31, 2003). SETTING: Academic level I trauma center practicing AE liberally.
      PATIENTS: Regardless of hemodynamic stability or the absence of a blood
      transfusion, patients with major pelvic fractures or significant pelvic hematomas
      on computed tomography were offered pelvic angiography with the intent to
      embolize. MAIN OUTCOME MEASURE: Angiographically confirmed pelvic bleeding,
      resulting in AE. RESULTS: Of 92 patients who underwent pelvic angiography, 55
      (60%) had bleeding found on angiography and underwent AE. Patients 60 years and
      older had a higher likelihood than younger patients to have bleeding identified
      and to undergo AE (16 [94%] of 17 patients vs 39 [52%] of 75 patients; P<.001).
      An age of 60 years or older was the only independent predictor of the need for
      AE. Of patients in this age group, two thirds had normal vital signs on hospital
      admission. Bleeding was controlled by AE in all patients (100% efficacy).
      CONCLUSIONS: Among blunt trauma patients with significant pelvic fractures, those
      60 years and older have a high likelihood of active retroperitoneal bleeding.
      Angiographic embolization should be offered liberally to patients in this age
      group, regardless of presumed hemodynamic stability.

PMID- 15249405
TI  - Does carotid stenting measure up to endarterectomy? A vascular surgeon's
      experience.
AB  - HYPOTHESIS: Carotid angioplasty and stenting seems to have equal or better
      outcomes in high-risk patients than carotid endarterectomy. DESIGN: Single-center
      case-control study. SETTING: University hospital tertiary referral center.
      PATIENTS: Individuals (n = 53) undergoing elective carotid angioplasty and
      stenting for cervical carotid stenosis (n = 57) between April 2001 and October
      2003. All patients were referred to and treated by the primary author (M.K.E.).
      RESULTS: Mean +/- SD age was 68.8 +/- 1.2 years (64% men [34] and 36% women
      [19]), and overall mean +/- SD rate of stenosis was 79% +/- 10%. Preprocedural
      neurologic symptoms were present in 42% of the group. Indications for treatment
      included prior neck surgery with irradiation (4), recurrent stenosis (19), and
      severe comorbidities (34). Duplex scanning 24 hours after stenting showed
      immediate mean percentage reductions in peaksystolic velocity and end diastolic
      velocity of 74% and 76%, respectively. After a 30-day follow-up period, there
      were no deaths and no major or minor strokes. One patient (1.7%) developed
      transient amaurosis fugax 12 hours after the procedure. Four patients (7.0%)
      experienced access-related complications. Intraoperative complications included 1
      seizure (1.7%) and 1 asystolic arrest (1.7%), both treated successfully. During
      follow-up, 3 cases of re-stenosis (5.0%) occurred. One asymptomatic occlusion
      (1.7%) was detected at the 6-month follow-up visit. There have been no late
      carotid-related complications or deaths. CONCLUSIONS: Vascular surgeons
      possessing advanced catheter-based skills can safely perform carotid angioplasty
      and stenting and can achieve perioperative results comparable with carotid
      endarterectomy. Determination of the true efficacy and durability of carotid
      angioplasty and stenting as compared with endarterectomy awaits ongoing
      randomized national trials.

PMID- 15249406
TI  - Double-blind, prospective, randomized study of warmed, humidified carbon dioxide
      insufflation vs standard carbon dioxide for patients undergoing laparoscopic
      cholecystectomy.
AB  - HYPOTHESIS: Patients undergoing warmed, humidified carbon dioxide (CO2)
      insufflation for laparoscopic cholecystectomy will (1) maintain a warmer
      intraoperative core temperature, (2) have their surgeon experience less fogging
      of the camera lens, and (3) have less postoperative pain than patients undergoing
      laparoscopic cholecystectomy with standard CO2 insufflation. DESIGN: A double
      blind, prospective, randomized study comparing patients undergoing laparoscopic
      cholecystectomy with standard CO2 insufflation vs those receiving warmed,
      humidified CO2 (Insuflow Filter Heater Hydrator; Lexion Medical, St Paul, Minn)
      was performed. Main variables included patient core temperature, postoperative
      pain, analgesic requirements, and camera lens fogging. RESULTS: One hundred one
      blinded patients (69 women, 32 men) undergoing laparoscopic cholecystectomy were
      randomized into 2 groups-52 receiving standard CO2 insufflation (group A) and 49
      receiving warmed, humidified CO2 (group B). Mean patient intraoperative core
      temperature change (group A decreased by 0.03 degrees C, group B increased by
      0.29 degrees C, P =.01) and mean abdominal pain (Likert scale, 0-10) at 14 days
      postoperatively (group A, 1.0; group B, 0.3; P =.02) were different. Other
      variables (camera lens fogging, early postoperative pain, narcotic requirements,
      recovery room stay, and return to normal activities) between groups were similar.
      CONCLUSION: While patients undergoing laparoscopic cholecystectomy with warmed,
      humidified CO2 had several advantages that were statistically significant, no
      major clinically relevant differences between groups A and B were evident.

PMID- 15249407
TI  - A simple method for safe identification of the facial nerve using palpable
      landmarks.
AB  - HYPOTHESIS: External palpable landmarks can be used to identify the facial nerve
      trunk quickly and safely. DESIGN: Prospective anatomical dissection study.
      SETTING: University department of human anatomy and university hospital. METHODS:
      A total of 40 human cadaver heads (79 facial nerves) were dissected by 2
      prosectors, a surgeon with experience in the anatomy of the parotid region
      (J.A.P.; n = 39) and a medical student with experience in anatomical dissection
      and basic knowledge of the facial nerve disposition (A.M.; n = 40). A 3-cm skin
      incision was made in the center of the triangle formed by the temporomandibular
      joint, the mastoid process, and the angle of the mandible, and dissection was
      continued deep until the main facial nerve trunk was identified. MAIN OUTCOME
      MEASURES: The time taken from the skin incision to the identification of the
      nerve was monitored with a chronometer by an independent observer. The distance
      between the predicted and actual position of the facial nerve was measured.
      RESULTS: In all cases, the facial nerve was identified and there were no
      significant differences in the dissection time between the 2 prosectors (144 vs
      148 seconds). The mean distance between the predicted and the actual position of
      the nerve was 1.42 mm. CONCLUSION: The proposed localization landmarks allowed a
      fast and safe identification of the facial nerve and may be of significant help
      during surgery around the parotid region.

PMID- 15249408
TI  - Choice of surveillance after hepatectomy for colorectal metastases.
AB  - HYPOTHESIS: By review of a reported series, is outcome related to surveillance
      after hepatectomy? DESIGN: We reviewed English-language literature indexed on
      MEDLINE from January 1, 1990, through December 31, 2002. Indexing terms were
      combinations of hepatectomy, colorectal metastases, and recurrence with
      prognostic, repeat, follow-up, or surveillance. STUDY SELECTION: Studies
      containing any of the following data fields were included: recurrence after
      hepatectomy, rates of repeat hepatectomy, 5-year survival (overall or disease
      free) after hepatectomy (initial or repeat), posthepatectomy surveillance
      protocol, and detection of recurrence by surveillance modality. DATA EXTRACTION:
      Data were taken directly from a small number of articles and pooled across
      studies for analysis. We highlighted difficulties in assessing data quality and
      validity as a caveat to the interpretation of the results. RESULTS: The rate of
      recurrence after hepatectomy was 58%, and the rate of hepatic recurrence was 30%.
      Repeat hepatectomy was performed in 9.6% of cases. Five-year survivals after
      initial and repeat hepatectomy were 29% and 38%, respectively. Many studies did
      not report their surveillance protocols. For those that did, computed tomography
      or ultrasonography with carcinoembryonic antigen measurement most commonly formed
      the basis of surveillance. No data related surveillance techniques to the
      outcomes of recurrence detection, repeat hepatectomy, or survival. CONCLUSIONS:
      This review confirmed the value of repeat hepatectomy for recurrent disease, but
      uncovered no direct evidence supporting any surveillance modalities. Further
      studies are clearly needed, and approaches to these are discussed.

PMID- 15249409
TI  - Randomized controlled trial of preservation or elective division of ilioinguinal
      nerve on open inguinal hernia repair with polypropylene mesh.
AB  - HYPOTHESIS: Our study aimed to evaluate the effect of preservation or elective
      division of the ilioinguinal nerve on pain and postoperative symptoms after open
      inguinal hernia repair with mesh. DESIGN: Double-blind, randomized trial.
      SETTING: Four public, government-financed hospitals in Italy. PATIENTS: From
      January 1, 1997, to June 30, 2002, 813 patients with primary inguinal hernia were
      randomly allocated to undergo inguinal hernia repair either with ilioinguinal
      nerve preservation (408 patients, group A) or elective transection (405 patients,
      group B). INTERVENTION: Hernia repair with sutureless apposition of a
      polypropylene mesh. MAIN OUTCOME MEASURES: The primary outcome was the evaluation
      of chronic pain 1 year after operation. Secondary outcomes were postoperative
      symptoms assessment at 1 week and 1, 6, and 12 months after operation. Telephone
      interview was performed 35.5 months (range, 12-59 months) after operation to
      assess the presence of chronic pain. RESULTS: Of the 302 group A and 291 group B
      patients who made an office visit 1 year postoperatively, pain was absent in 231
      (76.5%) and 213 (73%) (difference, 3.30%; 95% confidence interval, -3.68% to
      10.28%), mild in 55 (18%) and 60 (21%), moderate in 11 (4%) and 9 (3%), and
      severe in 5 (2%) and 9 (3%), respectively (P =.55; Pearson chi2(3) test). At 1
      month and 6-month follow-up visits, no difference was found between the 2 groups
      with respect to pain, but loss of pain or touch sensation were significantly
      greater when the ilioinguinal nerve was divided. One year after operation, the 2
      groups were also comparable with respect to loss of pain sensation, but touch
      sensation remained decreased in group B. At telephone interview, the presence of
      chronic pain was similar in both groups. CONCLUSIONS: Pain after open hernia
      repair with polypropylene mesh is not affected by elective division of the
      ilioinguinal nerve; sensory disturbances in the area of distribution of the
      transected nerve are significantly increased.

PMID- 15249410
TI  - Association of Streptococcus bovis bacteremia with colonic neoplasia and
      extracolonic malignancy.
AB  - BACKGROUND: The association between Streptococcus bovis bacteremia and colonic
      neoplasia is well described; however, the relationship between S bovis and
      neoplasia outside the colon has not been well evaluated. HYPOTHESIS: S bovis
      bacteremia may be associated with colonic neoplasia and extracolonic malignancy.
      DESIGN: Retrospective review of all documented cases of S bovis bacteremia
      identified by a search of computerized bacteriology records. SETTING: One
      tertiary referral hospital and 1 community hospital located in the same city.
      PATIENTS: Forty-five patients (41 adults, 4 children) with documented S bovis
      bacteremia during a 12-year period were identified. MAIN OUTCOME MEASURES:
      Available patient records were reviewed to identify the presence of colonic
      neoplasia, the use of gastrointestinal endoscopy, and the presence of
      gastrointestinal or extraintestinal malignancies. RESULTS: Seventeen patients
      (41% of adult patients) underwent colonoscopy. Colonic neoplasia was present in
      16 patients (39% of adults), with 3 of these patients having invasive colorectal
      cancer (7% of adults). Invasive cancer was present in 13 patients (32% of
      adults). Eight patients had malignant lesions arising within the gastrointestinal
      tract, and 5 patients had extraintestinal malignancies. CONCLUSION: S bovis
      bacteremia is associated with both colonic neoplasia and extracolonic malignancy.

PMID- 15249411
TI  - Sequential preoperative arterial and portal venous embolizations in patients with
      hepatocellular carcinoma.
AB  - HYPOTHESIS: Hepatic resection is the only curative treatment for large
      hepatocellular carcinoma (HCC). Sequential, preoperative, selective transcatheter
      arterial chemoembolization (TACE) and portal vein embolization (PVE) allow
      feasible and safe major hepatic resections to be performed in HCC patients with
      chronic liver disease. DESIGN: Retrospective cohort study. SETTING: University
      hospital. PATIENTS: Seventeen HCC patients who underwent preoperative PVE
      following selective TACE for planned major hepatic resections were enrolled. The
      indications for PVE were determined using the volumetric ratio of the future
      remnant liver parenchyma and the indocyanine green retention ratio at 15 minutes.
      INTERVENTION: Preoperative TACE and PVE. MAIN OUTCOME MEASURES: Tumor
      characteristics and blood test results before and after TACE and PVE, changes in
      the volumes of the liver segments after PVE, the feasibility of major hepatic
      resections, and short- and long-term patient prognoses. RESULTS: The liver
      function test results transiently worsened after TACE and PVE but returned to
      baseline levels within 1 (after TACE) or 2 (after PVE) weeks. Within 2 weeks
      after PVE, 22% +/- 4% hypertrophy of the nonembolized segments was obtained;
      subsequent major hepatic resections were feasible in 16 patients. Four minor
      complications (25%) were experienced postoperatively; however, liver failure did
      not occur. The 5-year overall and disease-free survival rates after curative
      resection were 55.6% and 46.7%, respectively. CONCLUSIONS: Sequential TACE and
      PVE contribute to both the broadening of surgical indications and the safety of
      major hepatic resections performed in HCC patients with damaged livers. The long
      term outcome of this treatment strategy is satisfactory.

PMID- 15249412
TI  - Colonic pacing: a therapeutic option for the treatment of constipation due to
      total colonic inertia.
AB  - HYPOTHESIS: The treatment of constipation caused by total colonic inertia is
      problematic and its results are unsatisfactory. We speculated that colonic pacing
      would initiate electric activity in the inertial colon and effect rectal
      evacuation. METHODS: Nine patients with constipation due to total colonic inertia
      (age range, 39-52 years; 7 women, 2 men) were enrolled in the study. One pacing
      electrode was applied to each of the 4 potential colonic pacemaker sites, and 2
      to 3 temporary recording electrodes were applied distally. A stimulator was
      embedded subcutaneously in the inguinal area. Home pacing was practiced after
      patients were trained; the recording electrodes were removed before home pacing
      was started. RESULTS: Colonic pacing evoked electric waves, which effected
      defecation in 6 of the 9 patients. Three of these 6 patients had spontaneous
      defecation after a few months of pacing, and their electrodes and stimulators
      were removed. In the other 3 of these 6 patients, the pacemakers are still in
      place and continue to effect rectal evacuation. Colonic pacing did not produce
      rectal evacuation in 3 patients and is believed to have failed because of an
      advanced stage of colonic inertia. CONCLUSION: Colonic pacing induced rectal
      evacuation in 66.6% of the patients with total colonic inertia. No complications
      were encountered. We suggest that colonic pacing be considered as a new
      therapeutic option in the treatment of total colonic inertia.

PMID- 15249413
TI  - The effects of gastric surgery on systemic ghrelin levels in the morbidly obese.
AB  - HYPOTHESIS: Circulating ghrelin, produced primarily in the stomach, is a powerful
      orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline
      postprandially. Early alterations in ghrelin levels in morbidly obese patients
      undergoing weight reduction surgery may be attributed to gastric partitioning.
      DESIGN AND PATIENTS: Thirty-four patients underwent Roux-en-Y gastric bypass with
      a completely divided gastroplasty to create a 15-mL vertically oriented gastric
      pouch. Eight other patients underwent other gastric procedures that did not
      involve complete division of the stomach, including 4 vertical banded
      gastroplasties and 4 antireflux surgical procedures. Six additional patients
      undergoing antireflux surgery served as lean control subjects. Plasma samples
      were obtained before surgery and immediately after surgery. In a substudy, plasma
      was collected after Roux-en-Y limb formation and after dividing the stomach to
      identify any changes in plasma ghrelin levels. SETTING: Tertiary university
      medical center. MAIN OUTCOME MEASURES: Ghrelin levels at different stages of
      surgical intervention. RESULTS: Mean +/- SEM preoperative and postoperative
      ghrelin levels in the gastric bypass group were 355 +/- 20 and 246 +/- 13 pg/mL,
      respectively (P<.001). In the vertical banded gastroplasty group and in all
      patients undergoing antireflux surgery, ghrelin levels were not significantly
      changed. CONCLUSIONS: Compared with morbidly obese humans, lean controls had
      significantly higher plasma ghrelin levels at baseline. A divided gastroplasty
      creating a small proximal gastric pouch results in significant early declines in
      circulating ghrelin levels that are not observed with other gastric procedures.
      This may explain, in part, the loss of hunger sensation and rapid weight loss
      observed following gastric bypass surgery.

PMID- 15249414
TI  - Homeopaths, surgery, and the Civil War: Edward C. Franklin and the struggle to
      achieve medical pluralism in the Union army.
AB  - An important aspect of the Union army medical corps throughout the Civil War was
      the clinical discord that pitted allopathic, or orthodox, physicians against
      sectarian, or unorthodox, physicians. Allopaths dominated the corps and its
      examining boards and consequently denied commissions as army surgeons to
      sectarian practitioners such as the homeopaths. This probably affected surgical
      manpower needs, since many well-trained homeopathic surgeons, like Edward C.
      Franklin, one of the nation's busiest and most prolific surgeons, wished to serve
      in the northern army but were unable to do so.

PMID- 15249415
TI  - Insufficient length of pulmonary artery introducer in an obese patient.
AB  - A 38-year-old, morbidly obese woman underwent surgery for debridement of
      necrotizing fasciitis of the abdominal wall. A pulmonary artery catheter was
      placed because of increasing fluid requirements. Despite multiple debridements
      and fluid resuscitation, the patient exhibited severe systemic inflammatory
      response. It was discovered that fluid placed in the introducer had extravasated
      into the subcutaneous tissues. In this obese patient, the pulmonary artery
      introducer was too short.

PMID- 15249416
TI  - Image of the month. Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 15249417
TI  - The genesis of nonoperative management of penetrating abdominal trauma.

PMID- 15249418
TI  - Minimally invasive surgery or minimal-incision thyroidectomy?

PMID- 15249419
TI  - Honey in tumor surgery.

PMID- 15249420
TI  - Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial
      benzodiazepine receptor ligand.
AB  - We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2
      phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine
      receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in
      various animal models. AC-5216 showed high affinity for MBRs prepared from rat
      whole brain (Ki 0.297 nm), rat glioma cells (IC50 3.04 nm) and human glioma cells
      (IC50 2.73 nm), but only negligible affinity for the other main receptors
      including central benzodiazepine receptors. AC-5216 produced anti-anxiety effects
      in the Vogel-type conflict test in rats, and in the light/dark box and social
      interaction tests in mice at 0.1-3, 0.003-0.01 and 0.01-0.3 mg kg(-1), p.o.,
      respectively. These effects of AC-5216 were antagonized by PK11195, an MBR
      antagonist. In the forced swimming test in rats, AC-5216 (3-30 mg kg(-1), p.o.)
      reduced the immobility time, and this effect was blocked by PK11195. AC-5216 had
      no myorelaxant effects, did not affect the memory or prolong hexobarbitone
      induced sleep in mice, even at doses as high as 1000 mg kg(-1), p.o. Although it
      did slightly prolong the ethanol-induced sleep time at 1000 mg kg(-1), AC-5216 (1
      100 mg kg(-1), p.o.) produced no distinct change in the rat electroencephalogram.
      These results indicate that AC-5216 produces anti-anxiety and antidepressant-like
      effects that are mediated by MBR, but does not cause the side effects normally
      associated with conventional benzodiazepines. Hence, AC-5216 shows potential for
      the treatment of stress-related disorders including anxiety and depression.

PMID- 15249421
TI  - Vanilloid receptors mediate adrenergic nerve- and CGRP-containing nerve-dependent
      vasodilation induced by nicotine in rat mesenteric resistance arteries.
AB  - Previous studies showed that nicotine induces adrenergic nerve-dependent
      vasodilation that is mediated by endogenous calcitonin gene-related peptide
      (CGRP) released from CGRP-containing (CGRPergic) nerves. The mechanisms
      underlying the nicotine-induced vasodilation were further studied. Rat mesenteric
      vascular beds without endothelium were contracted by perfusion with Krebs
      solution containing methoxamine, and the perfusion pressure was measured with a
      pressure transducer. Perfusion of nicotine (1-100 microm) for 1 min caused
      concentration-dependent vasodilation. Capsazepine (vanilloid receptor-1
      antagonist; 1-10 microm) and ruthenium red (inhibitor of vanilloid response; 1-30
      microm) concentration-dependently inhibited the nicotine-induced vasodilation
      without affecting the vasodilator response to exogenous CGRP. Nicotine-induced
      vasodilation was not inhibited by treatment with 3,4-dihydroxyphenylalanine
      (DOPA) receptor antagonist (l-DOPA cyclohexyl ester; 0.001-10 microm), dopamine
      D1 receptor-selective antagonist (SCH23390; 1-10 microm), dopamine D2 receptor
      antagonist (haloperidol; 0.1-0.5 microm), ATP P2x receptor-desensitizing agonist
      (alpha,beta-methylene ATP; 1-10 microm), adenosine A2 receptor antagonist (8(p
      sulfophenyl)theophylline; 10-50 microm) or neuropeptide Y (NPY)-Y1 receptor
      antagonist (BIBP3226; 0.1-0.5 microm). Immunohistochemical staining of the
      mesenteric artery showed dense innervation of CGRP- and vanilloid receptor-1
      positive nerves, with both immunostainings appearing in the same neuron. The
      mesenteric artery was also densely innervated by NPY-positive nerves. Double
      immunostainings showed that both NPY and CGRP immunoreactivities appeared in the
      same neuron of the artery. These results suggest that nicotine acts on
      presynaptic nicotinic receptors to release adrenergic neurotransmitter(s) or
      related substance(s), which then stimulate vanilloid receptor-1 on CGRPergic
      nerves, resulting in CGRP release and vasodilation.

PMID- 15249422
TI  - Red wine polyphenols induce EDHF-mediated relaxations in porcine coronary
      arteries through the redox-sensitive activation of the PI3-kinase/Akt pathway.
AB  - Red wine polyphenolic compounds (RWPCs) are potent inducers of endothelium
      dependent relaxations of coronary arteries, which involve both nitric oxide and
      endothelium-derived hyperpolarizing factor (EDHF). The EDHF-mediated relaxation
      to RWPCs is critically dependent on the formation of reactive oxygen species by a
      flavin-dependent enzyme. The aim of the present study was to determine the role
      of redox-sensitive protein kinases including p38 MAPK, ERK1/2 and PI3-kinase/Akt
      in RWPCs-induced EDHF-mediated relaxation. Porcine coronary artery rings were
      suspended in organ chambers for measurement of changes in isometric tension.
      Confluent cultures of porcine coronary artery endothelial cells were used to
      determine the phosphorylation level of p38 MAPK, ERK1/2 and Akt by Western blot
      analysis. All experiments were performed in the presence of indomethacin and
      Nomega-nitro-L-arginine. RWPCs caused pronounced endothelium-dependent
      relaxations, which were significantly reduced by wortmannin and LY294002, two
      inhibitors of PI3-kinase, and not affected by PD98059 (an inhibitor of ERK1/2
      kinase kinase) and SB203580 (an inhibitor of p38 MAPK). In contrast, wortmannin
      did not affect relaxations to bradykinin or levcromakalim. RWPCs elicited within
      minutes a sustained and concentration-dependent phosphorylation of p38 MAPK,
      ERK1/2 and Akt in endothelial cells. The phosphorylation of Akt in response to
      RWPCs was abolished by wortmannin and LY294002, and by the membrane-permeant
      analogue of superoxide dismutase Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin.
      The present findings demonstrate that RWPCs cause EDHF-mediated relaxations of
      coronary arteries; these responses are critically dependent on the redox
      sensitive activation of the PI3-kinase/Akt pathway in endothelial cells.

PMID- 15249423
TI  - Inhibitory effects of digoxin and digitoxin on corticosterone production in rat
      zona fasciculata-reticularis cells.
AB  - The aim of the present study was to investigate the direct effects and action
      mechanisms of digitalis on the production of corticosterone in rat adrenocortical
      cells. Male rats were challenged with digoxin (1 microg ml(-1) kg(-1)) in the
      presence or absence of adrenocorticotropin (ACTH, 5 microg ml(-1) kg(-1))
      administered by intravenous injection to the right jugular vein. Blood samples
      were collected at 0, 30, 60, and 120 min following the challenge. The
      concentration of corticosterone in the rat plasma samples was measured by
      radioimmunoassay. Zona fasciculata-reticularis (ZFR) cells in male rats were
      prepared and then incubated with or without digoxin or digitoxin in the presence
      or absence of ACTH (10(-9) m), forskolin (10(-7) m), 8-bromo-cyclic 3' : 5'
      adenosine monophosphate (10(-4) m), cyclopiazonic acid (CPA, 10(-5) m),
      trilostane (10(-6) m), 25-OH-cholesterol (10(-5) m), pregnenolone (10(-5) m),
      progesterone (10(-5) m), or deoxycorticosterone (10(-5) m) at 37 degrees C for 1
      h before collection of the media. Corticosterone or pregnenolone levels were
      measured by radioimmunoassay. A single injection of digoxin did not alter the
      basal level of plasma corticosterone, but did inhibit the level of plasma
      corticosterone released in response to ACTH in vivo. Administration of digoxin or
      digitoxin decreased both spontaneous and ACTH-stimulated release of
      corticosterone in vitro. Digoxin (10(-7)-10(-5) m) and digitoxin (10(-7)-10(-5)
      m), but not ouabain (10(-7)-10(-5) m), dose-dependently inhibited corticosterone
      production in response to forskolin and 8-Br-cyclic AMP in rat ZFR cells. Both
      digoxin (10(-6)-10(-5) m) and digitoxin (10(-6)-10(-5) m) attenuated
      corticosterone production in response to CPA. Digoxin (10(-5) m) or digitoxin
      (10(-5) m) inhibited cytochrome P450 side-chain cleavage enzyme (cytochrome
      P450scc) activity (catalyses conversion of cholesterol to pregnenolone in the
      presence of trilostane) in rat ZFR cells. The enzyme activity of 11 beta
      hydroxylase (catalyses conversion of deoxycorticosterone to corticosterone) in
      ZFR cells was also inhibited by the administration of digoxin (10(-5) m) or
      digitoxin (10(-5) m).10 These results together suggest that digoxin and digitoxin
      decrease the release of corticosterone by acting directly on ZFR cells via a Na+,
      K+-ATPase-independent mechanism involving the inhibition of the activities of
      adenylyl cyclase, cytochrome P450scc and 11 beta-hydroxylase, as well as the
      functioning of cyclic AMP and intracellular calcium.

PMID- 15249424
TI  - Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and
      its implication on the control of inactivation.
AB  - The voltage-dependent displacement of the scorpion Tityus serrulatus alpha-toxin
      Ts3 was investigated in native sodium channels of GH3 cells by examining the
      removal of its effects in toxin-free solution. Toxin at saturating concentration
      was pulsed (approximately 1 s) directly onto the cell, thus causing an eight-fold
      increase of the slow component (taus = 6 ms) of fast inactivation, and a three
      fold increase of the time constant of its fast component. At 0 mV, maximal
      conductance was achieved in cells before and after treatment with Ts3, and no
      displacement of the toxin could be detected. Toxin displacement occurred if
      stronger depolarising pulses (> 100 mV) were applied. The rate of displacement
      depended on the amplitude and duration of the pulses, and was not related with
      outward Na+ flux. We propose a model in which activation does not require
      complete movement of segment S4 of domain IV (IVS4) and that a more extensive
      movement of this segment is needed for normal fast inactivation. A kinetic model
      is presented that can account for the typical effects of site 3 toxins.

PMID- 15249425
TI  - Contribution of the p38MAPK signalling pathway to proliferation in human cultured
      airway smooth muscle cells is mitogen-specific.
AB  - We have investigated the role of p38MAPK in human airway smooth muscle (HASM)
      proliferation in response to thrombin and bFGF. The regulation of cyclin D1 mRNA,
      cyclin D1, cyclin E and p21Cip1 protein levels, and the extent of retinoblastoma
      protein (pRb) phosphorylation in response to activation of p38MAPK have also been
      examined. Two distinct inhibitors of p38MAPK, SB 203580 (10 microm) and SB 202190
      (10 microm), prevented bFGF (0.3-3 nm)-stimulated cell proliferation, but had no
      effect on the response to thrombin (0.3-3 U ml(-1)). In cells incubated with
      thrombin or bFGF for 20 h, there was an increase in p38MAPK phosphorylation in
      response to bFGF, but not to thrombin. Thrombin and bFGF-stimulated increases in
      ERK phosphorylation and cyclin D1 mRNA and protein levels were not influenced by
      SB 203580 pre-treatment. Similarly, cyclin E and p21Cip1 protein levels, measured
      after 20 h incubation with mitogen, did not appear to be regulated by SB 203580
      (10 microm). Although both thrombin and bFGF significantly increased levels of
      pRb phosphorylation, SB 203580 (10 microm) inhibited only bFGF-stimulated pRb
      phosphorylation. In addition, SB 203580 (10 microm) selectively inhibited bFGF
      stimulated DNA synthesis, suggesting that the antimitogenic actions of SB 203580
      on pRb phosphorylation cause cell cycle arrest at late G1 phase. In conclusion,
      these results indicate that p38MAPK is involved in bFGF-, but not in thrombin
      stimulated HASM proliferation. The activation of the p38MAPK pathway by bFGF, but
      not by thrombin, regulates the phosphorylation of pRb without influencing cyclin
      D1 expression.

PMID- 15249426
TI  - Role of nuclear factor-kappaB and heme oxygenase-1 in the mechanism of action of
      an anti-inflammatory chalcone derivative in RAW 264.7 cells.
AB  - The synthetic chalcone 3',4',5',3,4,5-hexamethoxy-chalcone (CH) is an anti
      inflammatory compound able to reduce nitric oxide (NO) production by inhibition
      of inducible NO synthase protein synthesis. In this work, we have studied the
      mechanisms of action of this compound. CH (10-30 microm) prevents the
      overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide
      (1 microg ml(-1)) due to the inhibition of nuclear factor kappaB (NF-kappaB)
      activation. We have shown that treatment of cells with CH results in diminished
      degradation of the NF-kappaB-IkappaB complex leading to inhibition of NF-kappaB
      translocation into the nucleus, DNA binding and transcriptional activity. We also
      demonstrate the ability of this compound to activate NfE2-related factor (Nrf2)
      and induce heme oxygenase-1 (HO-1). Our results indicate that CH determines a
      rapid but nontoxic increase of intracellular oxidative species, which could be
      responsible for Nrf2 activation and HO-1 induction by this chalcone derivative.
      This novel anti-inflammatory agent simultaneously induces a cytoprotective
      response (HO-1) and downregulates an inflammatory pathway (NF-kappaB) with a
      mechanism of action different from antioxidant chalcones.

PMID- 15249427
TI  - Aminoguanidine prevents age-related deterioration in left ventricular-arterial
      coupling in Fisher 344 rats.
AB  - In recent studies, aminoguanidine (AG), an inhibitor of advanced glycation
      endproducts, has been identified as a prominent agent that can prevent the age
      related aortic stiffening and cardiac hypertrophy. The aim of this study was to
      determine whether AG had effects on the left ventricular (LV)-arterial coupling
      in aged Fisher 344 rats in terms of the ventricular and arterial chamber
      properties. Normotensive rats were treated from 18 to 24 months with AG (1 g l(
      1) in drinking water) and compared with a control group. LV pressure and
      ascending aortic flow signals were recorded to construct the ventricular and
      arterial end-systolic pressure-stroke volume relationships to calculate LV end
      systolic elastance (Ees) and effective arterial volume elastance (Ea),
      respectively. The optimal afterload (Qload) determined by the ratio of Ea to Ees
      was used to measure the efficiency of mechanical energy transferred from the left
      ventricle to the arterial system. In comparison with the 6-month-old rats, the 24
      month-old animals had decreased Ees, at 567.4 +/- 26.7 vs 639.0 +/- 20.7 mmHg ml(
      1), decreased Ea, at 411.5 +/- 18.6 vs 577.9 +/- 15.7 mmHg ml(-1), and decreased
      Q(load), at 0.9428 +/- 0.0024 vs 0.9962 +/- 0.0014. Treatment with AG for 6
      months did not significantly affect Ees; however, when normalized to LV weight
      (i.e., Eesn = Ees/LV weight), Eesn showed a significant rise of 22.8%, suggesting
      that AG may retard the aging process on the intrinsic contractility of the left
      ventricle. On the other hand, the decrease in Ea in aging rats was prevented by
      AG, as reflected in the increase of 19.7% in this variable (P < 0.05). The 24
      month-old treated rats also exhibited a significant rise of 21.6% in Ea/Ees,
      causing an increase of 5.2% in Qload (P < 0.05). We conclude that in healthy
      older Fisher 344 rats without diabetes, long-term treatment with AG may improve
      both the arterial and ventricular function and optimize the matching condition
      for the left ventricular-arterial coupling.

PMID- 15249428
TI  - Levetiracetam inhibits Na+-dependent Cl-/HCO3- exchange of adult hippocampal CA3
      neurons from guinea-pigs.
AB  - The novel anticonvulsant levetiracetam (LEV) was tested for effects on
      bioelectric activity and intracellular pH (pHi) regulation of hippocampal CA3
      neurons from adult guinea-pigs. In 4-aminopyridine-treated slices, LEV (10-100
      microm) reduced the frequency of action potentials and epileptiform bursts of CA3
      neurons by 30-55%, while the shape of these potentials remained largely
      unchanged. Suppressive effects were reversed by an increase of pHi with
      trimethylamine (TMA). Using BCECF-AM-loaded slices, we found that LEV (10-50
      microm) reversibly lowered neuronal steady-state pHi by 0.19 +/- 0.07 pH units in
      the presence of extracellular CO2/HCO3- buffer. In the nominal absence of
      extracellular CO2/HCO3- or in Na+-free CO2/HCO3(-)-buffered solution, LEV had no
      effect on steady-state pHi. Recovery of pHi subsequent to ammonium prepulses
      remained unchanged in the absence of CO2/HCO3- buffer, but was significantly
      reduced by LEV in the presence of CO2/HCO3- buffer. These findings show that LEV
      inhibits HCO3(-)-dependent acid extrusion, but has no effect on Na+/H+ exchange.
      LEV did not affect Na+-independent Cl-/HCO3- exchange because intracellular
      alkalosis upon withdrawal of extracellular Cl- remained unchanged. These data
      show that LEV at clinically relevant concentrations inhibits Na+-dependent Cl
      /HCO3- exchange, lowers neuronal pHi, and thereby may contribute to its
      anticonvulsive activity.

PMID- 15249429
TI  - Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal
      transit in lipopolysaccharide-treated rats.
AB  - The biological effects of cannabinoids (CB) are mediated by CB(1) and CB(2)
      receptors. The role of CB(2) receptors in the gastrointestinal tract is
      uncertain. In this study, we examined whether CB(2) receptor activation is
      involved in the regulation of gastrointestinal transit in rats. Basal and
      lipopolysaccharide (LPS)-stimulated gastrointestinal transit was measured after
      instillation of an Evans blue-gum Arabic suspension into the stomach, in the
      presence of specific CB(1) and CB(2) agonists and antagonists, or after treatment
      with inhibitors of mediators implicated in the transit process. In control rats a
      CB(1) (ACEA; 1 mg kg(-1)), but not a CB(2) (JWH-133; 1 mg kg(-1)), receptor
      agonist inhibited basal gastrointestinal transit. The effects of the CB(1)
      agonist were reversed by the CB(1) antagonist AM-251, which alone increased basal
      transit. LPS treatment increased gastrointestinal transit. This increased transit
      was reduced to control values by the CB(2), but not the CB(1), agonist. This
      inhibition by the CB(2) agonist was dose dependent and prevented by a selective
      CB(2) antagonist (AM-630; 1 mg kg(-1)). By evaluating the inhibition of LPS
      enhanced gastrointestinal transit by different antagonists, the effects of the
      CB(2) agonist (JWH-133; 1 mg kg(-1)) were found to act via cyclooxygenase, and to
      act independently of inducible nitric oxide synthase (NOS) and platelet
      activating factor. Interleukin-1 beta and constitutive NOS isoforms may be
      involved in the accelerated LPS transit. The activation of CB(2) receptors in
      response to LPS is a mechanism for the re-establishment of normal
      gastrointestinal transit after an inflammatory stimulus.

PMID- 15249430
TI  - Inflammation and obstructive sleep apnea syndrome: how many ways do I look at
      thee?

PMID- 15249431
TI  - Invasive management of patients with ST elevation myocardial infarction with > 12
      h delay in presentation: the question remains unanswered.

PMID- 15249432
TI  - Timing is everything.

PMID- 15249433
TI  - Innovations in lung volume reduction: the non-cutting edge.

PMID- 15249434
TI  - Extending the uses of ECMO.

PMID- 15249436
TI  - Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of
      children with obstructive sleep apnea syndrome or recurrent infection.
AB  - BACKGROUND: Recurrent tonsillitis and sleep apnea are the major indications for
      tonsillectomy in children. We hypothesized that the recurrent vibration in the
      upper airway of snoring children would promote inflammatory changes in the
      tonsillar tissue and would lead to the up-regulation of cysteinyl leukotriene
      (LT) receptors (Rs). OBJECTIVE: To assess the expression patterns of the human LT
      Rs in children undergoing tonsillectomy, and compare those patterns in children
      having recurrent throat infections (RIs) and children with obstructive sleep
      apnea syndrome (SA). METHODS: Tonsillar tissue from 17 children with SA and 13
      with RIs was subjected to quantitative polymerase chain reaction using specific
      primers for LT1-R and LT2-R, and to immunohistochemistry and Western blotting for
      protein expression of LT1-R and LT2-R. RESULTS: Messenger RNA encoding for the
      expression of LT1-R and LT2-R was detected in the tonsils of all children.
      Immunoblots revealed significantly higher expressions of LT1-R and LT2-R in the
      tonsils of children with SA. The topographic pattern of both receptors differed
      among the tonsils of children with SA and RI. CONCLUSION: LT1-R and LT2-R are
      expressed in pediatric tonsillar tissue, are more abundant in SA patients, and
      demonstrate a specific topographic pattern of expression. These findings suggest
      that an inflammatory process involving LT expression and regulation occurs in
      children with SA.

PMID- 15249437
TI  - Prevalence of snoring and symptoms of sleep-disordered breathing in primary
      school children in istanbul.
AB  - STUDY OBJECTIVES: Snoring during sleep is an important manifestation of
      obstructive sleep apnea syndrome (OSAS). Although clinical history is not
      sufficiently sensitive and specific to distinguish primary snoring from OSAS,
      snoring is indicative of upper airway obstruction and may be associated with the
      presence of diurnal symptoms. Our study aims were to determine the prevalence of
      snoring in primary school children in Istanbul, and to evaluate the diurnal
      symptoms and conditions that may be associated with sleep problems. DESIGN,
      SETTING, AND SUBJECTS: A parental questionnaire was used to assess the sleep and
      wake behavioral patterns in children. Eight representative schools in each of 9
      school districts randomly selected from the 32 school districts in Istanbul were
      visited. RESULTS: The response rate was 78.1%; 2,147 of 2,746 questionnaires were
      fully completed, returned, and analyzed. The prevalence of habitual snoring was
      7.0%. Habitual snorers had significantly more nighttime symptoms, such as
      observed apneas (odds ratio [OR], 16.9; 95% confidence interval [CI], 10.0 to
      28.8; p < 0.0001), difficulty breathing (OR, 17.8; CI, 10.9 to 29.2; p < 0.0001),
      restless sleep, parasomnias, and nocturnal enuresis, compared to occasional and
      nonsnorers. There were also increased prevalence of daytime symptoms, such as
      falling asleep while watching television (OR, 1.8; CI, 0.9 to 3.7; p = 0.01) and
      in public places (OR, 2.1; CI, 1.2 to 3.8; p = 0.03), and hyperactivity (OR, 2.7;
      CI, 1.8 to 3.9; p < 0.0001). Exposure to cigarette smoke and the presence of
      asthma and hay fever increased the likelihood of habitual snoring. Children with
      a higher risk for OSAS (habitual snoring, apnea, and difficulty breathing during
      sleep) were also compared to nonsnorers. Although nighttime symptoms were more
      likely in the high-risk group, the risk of daytime symptoms increased as well.
      CONCLUSIONS: Habitual snoring is a significant problem for children and may be
      associated with diurnal symptoms. Exposure to cigarette smoke at home and the
      presence of asthma and hay fever increase the likelihood of habitual snoring.

PMID- 15249438
TI  - Efficacy of flow- vs impedance-guided autoadjustable continuous positive airway
      pressure: a randomized cross-over trial.
AB  - STUDY OBJECTIVES: Autoadjustable continuous positive airway pressure (CPAP)
      devices are increasingly used in the treatment of obstructive sleep apnea (OSA).
      Since different measurements of upper airway obstruction are applied, it is
      uncertain whether these devices are equally effective in controlling sleep
      disordered breathing. Hypothesizing that differences in therapeutic efficacy were
      to come out, we compared the performance of the AutoSet device (ResMed; Sydney,
      Australia), which features autoadjustable positive airway pressure (APAP) guided
      by detection of flow limitation (APAPfl), with the SOMNOsmart device (Weinmann;
      Hamburg, Germany), which features APAP guided by the forced oscillation technique
      (APAPfot). DESIGN: A double-blind, randomized, cross-over trial. SETTING: The
      sleep disorders center and sleep laboratory of a university hospital. PATIENTS
      AND INTERVENTIONS: An overnight CPAP autotitration procedure was performed in 30
      patients with OSA. A split-night protocol allowed that each patient used both
      devices. MEASUREMENTS AND RESULTS: Using polysomnography, sleep, indexes of sleep
      disordered breathing, snoring, and CPAP levels were recorded. No significant
      differences were found in conventional sleep variables. While the apnea-hypopnea
      index (AHI) was lower with APAPfl (3.5 +/- 5.6/h) as compared to APAPfot (9.9 +/-
      31.0/h), the difference was not statistically significant (mean +/- SD). The
      snoring index, however, was significantly lower with APAPfl (35.3 +/- 53.7/h vs
      111.6 +/- 175.4/h, respectively; p = 0.01). The median and 95th percentile
      pressure levels rose from wakefulness to sleep in APAPfl, but decreased in
      APAPfot. Higher pressure variability was present in the latter method.
      CONCLUSIONS: These findings suggest that the APAPfl is superior to APAPfot in the
      control of snoring. While a lower AHI was achieved with APAPfl, at the expense of
      a higher median pressure but less pressure variability, the difference with
      APAPfot was not statistically significant.

PMID- 15249439
TI  - Constant vs auto-continuous positive airway pressure in patients with sleep apnea
      hypopnea syndrome and a high variability in pressure requirement.
AB  - STUDY OBJECTIVES: Auto-continuous positive airway pressure (CPAP) has been
      reported to have no more efficacy than constant CPAP in unselected patients with
      sleep apnea hypopnea syndrome (SAHS). The aim of this study was to evaluate
      patients judged to be good candidates for auto-CPAP because of a high within
      night variability in pressure requirement. DESIGN: Single-blind, randomized,
      cross-over study (2 x 8 weeks) to compare auto-CPAP with constant CPAP. PATIENTS:
      Outpatients with moderate-to-severe SAHS attending the chest clinic.
      INTERVENTIONS: Patients were equipped at home in the auto-CPAP mode (model
      GK418A; Malinckrodt; Nancy, France), using a 4- to 14-cm H(2)O pressure range.
      Those individuals having a high within-night variability in pressure requirement,
      assessed at the end of a 14-day run-in period, were included in the cross-over
      study. Auto-CPAP was compared with constant CPAP (according to a titration night
      in the sleep laboratory) in terms of compliance, efficacy on apneas (assessed
      from the pressure monitor), and sleepiness (assessed on the Epworth sleepiness
      scale). MEASUREMENTS AND RESULTS: Of 90 consecutive patients with SAHS, 27
      patients were selected for a within-night variability in pressure requirement
      exceeding a given threshold. After completion of the cross-over, 24 patients were
      evaluable. The median percentage of nights the machine was used was 95.5% (range,
      45 to 100%) on constant CPAP, and 96.5% (range, 40 to 100%) on auto-CPAP; the
      median apnea index recorded by the device was 0.40/h (range, 0 to 2.40/h) on
      constant CPAP, and 0.45/h (range, 0 to 5.80/h) on auto-CPAP (differences not
      significant). The mean Epworth sleepiness score was significantly (p < 0.01)
      lower on auto-CPAP (5.1; SD, 2.8) than on constant CPAP (6.1; SD, 2.8).
      CONCLUSIONS: In patients selected for a high within-night variability in pressure
      requirement, auto-CPAP administered via a GK418A device was equivalent to
      constant CPAP based on a titration night in the sleep laboratory. Subjective
      ratings for sleepiness were slightly lower on auto-CPAP.

PMID- 15249440
TI  - Delayed post-myocardial infarction invasive measures, helpful or harmful? A
      subgroup analysis.
AB  - BACKGROUND: In patients who have experienced acute myocardial infarction (MI),
      primary percutaneous coronary intervention (PCI) has been shown to be of benefit
      in terms of clinical outcomes. However, the value of performing routine PCI in
      patients with early MI (ie, an MI occurring > 12 h to < or = 7 days before
      patient presentation) or recent MI (ie, an MI occurring > or = 8 days to < 30
      days before patient presentation) has not been established. The purposes of this
      prospective observational study were to evaluate the impact of PCI on outcomes,
      and to delineate the predictors of lack of response to reperfusion and the
      prognostic determinants in patients with this clinical condition. METHODS AND
      RESULTS: A total of 377 consecutive unselected patients who had experienced early
      or recent MI underwent PCI. Successful reperfusion (ie, Thrombolysis in
      Myocardial Infarction flow grade 3 of the infarct-related artery [IRA]) was
      achieved in 90.2% of patients. By multiple stepwise logistic regression analysis,
      high-burden thrombus formation (odds ratio [OR], 15.53; 95% confidence interval
      [CI], 6.09 to 39.60; p < 0.0001) in the IRA, early PCI (ie, < or = 3 days) [OR,
      4.10; 95% CI, 1.79 to 7.36; p = 0.0008], advanced congestive heart failure (CHF)
      [OR, 4.10; 95% CI, 1.70 to 9.91; p = 0.002], and diabetes (OR, 3.03; 95% CI, 1.03
      to 7.06; p = 0.010) were independent predictors for lack of response to
      reperfusion. The 30-day mortality rate was 6.8%. The only variables that were
      independently related to the 30-day mortality rate were advanced CHF (OR, 29.85;
      95% CI, 7.84 to 113.7; p < 0.0001), lack of response to reperfusion (OR, 7.57;
      95% CI, 2.29 to 25.07; p = 0.0009), early PCI (OR, 4.81; 95% CI, 1.60 to 14.41; p
      = 0.005), and multivessel disease (OR, 9.22; 95% CI, 1.63 to 52.04; p = 0.0119).
      The surviving 351 patients were discharged from the hospital and followed-up for
      a mean (+/- SD) 38.9 +/- 14.2 months. Coronary angiographic follow-up was
      performed in 285 patients (81.2%). Restenosis of the IRA was found in 101
      patients (35.4%). Reinterventions of the IRA were required in 69 patients
      (24.2%). Follow-up measurements of left ventricular ejection fraction (LVEF)
      showed significantly more improvement than the initial LVEF (59.3 +/- 13.8% vs
      50.4 +/- 13%; p < 0.0001). The total cumulative mortality rate after hospital
      discharge was 6.5% for the entire group. Only advanced CHF (OR, 3.46; 95% CI,
      1.26 to 9.52; p = 0.016) and old age (ie, > or = 70 years of age) [OR, 4.41; 95%
      CI, 1.59 to 12.24; p = 0.004] were independent predictors of long-term mortality.
      CONCLUSION: The performance of PCI on > or = day 4 in patients after they had
      experienced an MI was safe and had a high rate of success. The clinical benefits
      of a relative low mortality rate associated with successful PCI for patients with
      early and recent MI was maintained during the long-term follow-up. However,
      patients with advanced CHF along with old age continued to have a poor prognosis.

PMID- 15249441
TI  - Comparison of baseline characteristics, clinical features, angiographic results,
      and early outcomes in men vs women with acute myocardial infarction undergoing
      primary coronary intervention.
AB  - BACKGROUND: Women have had a higher early mortality rate than men after acute
      myocardial infarction (AMI) in the prethrombolytic and thrombolytic eras. Primary
      percutaneous coronary intervention (PCI) has been shown to significantly improve
      survival of patients with AMI, and to be superior to thrombolytic therapy in
      terms of immediate restoration of normal flow in the infarct-related artery and
      reduction of recurrent ischemic events. However, the effect of primary PCI on
      early outcomes of women vs men remains unknown. Therefore, we examined whether
      there was any difference in term of 30-day mortality between women and men after
      primary PCI. METHODS AND RESULTS: Between May 1993 and April 2002, primary PCI
      was performed in 1,032 consecutive patients (15.3% women and 84.7% men) with AMI.
      The overall successful reperfusion (final Thrombolysis in Myocardial Infarction
      grade 3 flow) and 30-day morality rates were 84.0% and 8.5%, respectively. The
      rate of successful reperfusion did not differ between women and men (84.8% vs
      83.9%, p = 0.77). However, mortality at 30 days was significantly higher in women
      than in men (14.6% vs 7.4%, p = 0.003). In comparison with men, women were older;
      had significantly higher incidences of hypertension, diabetes mellitus, complete
      atrioventricular block, and right ventricular infarction; and had longer times of
      reperfusion (all p values < 0.05). During hospitalization, advanced congestive
      heart failure (New York Heart Association class 3 or greater), free wall rupture,
      and major bleeding complications were more likely to occur in women than in men
      (all p values < 0.05). Compared with men, the unadjusted odds ratio for 30-day
      death among women was 2.12 (95% confidence interval [CI], 1.27 to 3.53). After
      adjusting for age, the odds ratio was substantially reduced to 1.66 (95% CI, 0.98
      to 2.79). Further adjustment for age and other variables further reduced the odds
      ratio to 1.06 (95% CI, 0.53 to 2.14). CONCLUSIONS: A gender gap of 30-day
      mortality existed between women and men with AMI that could not be altered by
      primary PCI. However, this gap was only an apparent one, and was not truly
      related to gender alone. In comparison with men, women were older, had
      significantly higher incidences of comorbidities and major untoward clinical
      events, and had longer times of reperfusion, which could help explain why the 30
      day mortality rate was higher in women than in men.

PMID- 15249442
TI  - Increased plasma levels of soluble P-selectin in rheumatic mitral stenosis.
AB  - BACKGROUND: Previous studies have demonstrated that platelet activation occurs in
      peripheral blood of patients with rheumatic mitral stenosis (MS). However, in
      patients with MS, the plasma level of soluble P-selectin (a marker of platelet
      activation) remains unsettled. METHODS AND RESULTS: A total of 20 patients with
      symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty (PTMV)
      were studied (group 1; 16 patients in permanent atrial fibrillation, and 4
      patients in sinus rhythm). The plasma levels of soluble P-selectin in the femoral
      vein and artery, and right and left atria before PTMV and those in the peripheral
      venous blood at the 1-week and 4-week follow-ups after PTMV were determined by
      solid-phase, sandwich, enzyme-linked immunosorbent assay. The mitral valve area
      was calculated by means of the Doppler pressure half-time method. In addition, we
      measured plasma concentrations of soluble P-selectin in the peripheral venous
      blood samples obtained from 22 control patients (including 14 healthy volunteers
      in sinus rhythm [group 2] and 8 patients in permanent lone atrial fibrillation
      [group 3]). The plasma levels of soluble P-selectin were significantly elevated
      in group 1 patients (49.78 +/- 37.72 ng/mL) [mean +/- SD] compared with group 2
      (25.52 +/- 15.38 ng/mL) and group 3 patients (32.17 +/- 14.18 ng/mL) [p < 0.005].
      In group 1 patients, the plasma levels of soluble P-selectin in the left atrium
      did not significantly differ from those in the right atrium, femoral vein, or
      femoral artery (p = 0.05). The area of mitral valve increased significantly after
      PTMV (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2), p < 0.0001). The mean left
      atrial pressure fell significantly and immediately after PTMV (23.0 +/- 5.1 mm Hg
      vs 17.6 +/- 5.9 mm Hg, p < 0.0001). The peripheral venous plasma levels of
      soluble P-selectin obtained before PTMV did not significantly fall after PTMV
      (before, 49.8 +/- 37.7 ng/mL; 10 min after, 39.8 +/- 19.1 ng/mL; 1 week after,
      46.1 +/- 20.8 ng/mL; and 4 weeks after, 41.2 +/- 15.9 ng/mL; p = 0.145).
      CONCLUSIONS: The venous plasma levels of soluble P-selectin in patients with
      moderate-to-severe MS were significantly higher than those in healthy volunteers
      or patients with lone atrial fibrillation. In addition, in patients with MS,
      there was no difference in the plasma levels of soluble P-selectin between the
      left and right atrial blood and between peripheral and atrial blood. Moreover,
      there was no change in soluble P-selectin levels as a result of PTMV.

PMID- 15249443
TI  - Asthma as a risk factor for COPD in a longitudinal study.
AB  - BACKGROUND: For several years, asthma and COPD have been regarded as distinct
      entities, with distinct clinical courses. However, despite distinctive
      physiologic features at the time of diagnosis, and different risk factors, the
      two diseases over time may develop features that are quite similar. STUDY
      OBJECTIVE: To evaluate the association between physician-diagnosed asthma and the
      subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson,
      AZ. DESIGN AND METHODS: A prospective observational study. Participants completed
      up to 12 standard respiratory questionnaires and 11 spirometry lung function
      measurements over a period of 20 years. Survival curves (with time to development
      of COPD as the dependent variable) were compared between subjects with asthma and
      subjects without asthma at the initial survey. RESULTS: Subjects with active
      asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156)
      or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with
      nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring
      symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17
      times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83),
      and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84),
      even after adjusting for smoking history and other potential confounders.
      CONCLUSIONS: Physician-diagnosed asthma is significantly associated with an
      increased risk for CB, emphysema, and COPD.

PMID- 15249444
TI  - Beta 2-adrenergic receptor polymorphisms and haplotypes are associated with
      airways hyperresponsiveness among nonsmoking men.
AB  - STUDY OBJECTIVE: To investigate the relationship of common single nucleotide
      polymorphisms (SNPs) of the beta(2)-adrenergic receptor (AR) gene at codons 16
      and 27, and the intermediate phenotype of airways hyperresponsiveness. DESIGN: A
      case-control study in 543 white men (152 case patients and 391 control subjects),
      who were nested in an ongoing longitudinal cohort. SETTING: Subjects were
      selected from the Normative Aging Study, an ongoing longitudinal cohort of
      healthy aging. PARTICIPANTS: Case patients were defined as those having a
      positive response to methacholine challenge testing. Control subjects were
      selected among those who did not have a diagnosis of asthma and who had no
      response to methacholine. RESULTS: There was a trend for an association of the
      Arg16 SNP genotype with airways hyperresponsiveness (odds ratio, 1.25; 95%
      confidence interval, 0.96 to 1.64 [in an additive model]). In stratified
      analyses, the effect of the Arg16 variant was seen mainly among nonsmokers.
      Smokers had increased risks for airway hyperresponsiveness regardless of genotype
      at either SNP. Using a program to estimate haplotype frequencies, three common
      haplotypes were identified. Adjusting for age, baseline FEV(1), serum IgE level,
      and smoking status, the Gly16/Gln27 haplotype was negatively associated with
      airways hyperresponsiveness in the full complement of case patients and control
      subjects (score statistic, - 2.43; p = 0.02). The effect of the beta(2)-AR
      haplotypes was much stronger among lifelong nonsmokers, among whom the
      Gly16/Gln27 haplotype remained negatively associated with airways
      hyperresponsiveness (score statistic, - 3.114; p = 0.002), whereas the
      Arg16/Gln27 haplotype was positively associated with airways hyperresponsiveness
      (score statistic, 3.142; p = 0.002). No effects were seen among ever-smokers.
      CONCLUSIONS: In this cohort of middle-aged to older white men, beta(2)-AR
      polymorphisms were associated with airways hyperresponsiveness, particularly
      among lifelong nonsmokers. Our results illustrate an instance in which greater
      power is obtained by performing haplotype analyses as opposed to single SNP
      analysis.

PMID- 15249445
TI  - Treatment patterns in the months prior to and after asthma-related emergency
      department visit.
AB  - BACKGROUND: There are 2 million asthma-related emergency department (ED) events
      each year in the United States. The underrecognition and undertreatment of asthma
      is believed to be associated with this high level of morbidity. This study was
      designed to describe the treatment patterns in the year prior to the ED event and
      for 2 months after the event. METHODS: This retrospective observational study
      utilized an integrated managed care database that contained administrative claims
      from > 20 managed care plans across the United States. All patients with at least
      one ED visit for asthma during 2001 were included. Patients were required to have
      data available 12 months prior to and 2 months following the ED visit of
      interest, and were excluded if they had made an asthma-related ED visit within 12
      months of the identified event. RESULTS: There were 12,636 patients identified
      with an asthma-related ED visit. In the year prior to the ED event, 25.1% of the
      patients received an inhaled corticosteroid (ICS), 29.9% received an oral
      corticosteroid (OCS), and 53.5% received a short-acting beta-agonist (SABA).
      Overall, there were three albuterol units dispensed for every ICS unit dispensed
      in the 12-month period prior to the ED event. Ninety-four percent of patients had
      made an office visit in the prior year, but only 13.3% underwent spirometry
      testing. Prescriptions dispensed for ICSs and OCSs increased 2.6-fold and 7.5
      fold, respectively, in the month after the ED event, and dispensing rates
      reverted approximately to baseline rates by the second month after the index ED
      event. CONCLUSION: This study demonstrates the dependence of this population on
      the use of rescue medications, including SABA and OCS, to treat their asthma.
      Furthermore, the ED event resulted in only an incremental short-term improvement
      in ICS-containing controller treatment.

PMID- 15249446
TI  - The Veterans Short Form 36 questionnaire is predictive of mortality and health
      care utilization in a population of veterans with a self-reported diagnosis of
      asthma or COPD.
AB  - STUDY OBJECTIVE: Measures of health-related quality of life (HRQL) correlate with
      disease stage in persons with COPD. However, as their predictive capacity for
      mortality or medical utilization is less well defined, we sought to examine the
      relationship of a general measure of HRQL and outcomes in persons with
      obstructive lung disease. DESIGN: Prospective cohort study. SETTING: Upper
      Midwest Veterans Integrated Service Network (VISN)-13. PARTICIPANTS: All veterans
      in VISN-13 (n = 70,017) were surveyed with the Veterans Short Form 36 (SF-36V).
      Persons with reported asthma or COPD who completed the SF-36V formed the study
      cohort (n = 8,354). MEASUREMENTS AND RESULTS: For purposes of analysis,
      individuals were divided into quartiles of HRQL according to their physical
      component summary (PCS) and mental component summary (MCS), values derived from
      the SF-36V. Outcomes of mortality, hospitalization, and outpatient visits were
      recorded for 12 months after the survey. Outpatient utilization was dichotomized
      into high vs low use, with high use being defined as the upper quartile of visits
      in the 12 months prior to survey mailing. The study cohort had a mean age of 65
      years and was largely male (95%), both consistent with a veteran population.
      After correcting for potential confounding factors through multivariable
      regression, the PCS was independently predictive of death, hospitalization, and
      high outpatient utilization. When using the first quartile of PCS as the
      reference population, those in the fourth quartile of PCS had a hazard ratio for
      death of 5.47 (95% confidence interval [CI], 3.63 to 8.26). Similarly, the odds
      ratios for hospitalization, high primary care visits, and high specialty medicine
      visits in the fourth quartile of PCS were 1.82 (95% CI, 1.51 to 2.19), 1.54 (95%
      CI, 1.26 to 1.87), and 1.46 (95% CI, 1.21 to 1.78), respectively. The MCS,
      through multivariable regression, was predictive of death but unassociated with
      subsequent hospitalization or high outpatient utilization. CONCLUSION: HRQL, as
      assessed by the SF-36V, is an independent predictor of mortality,
      hospitalization, and outpatient utilization in persons with self-reported
      obstructive lung disease.

PMID- 15249447
TI  - Micrococcus-associated central venous catheter infection in patients with
      pulmonary arterial hypertension.
AB  - STUDY OBJECTIVES: To determine the incidence of catheter-related infection in
      patients with pulmonary arterial hypertension (PAH) receiving epoprostenol (EPO),
      and to note an etiologic role for Micrococcus spp, which is rarely reported as a
      pathogen in the medical literature. DESIGN: Observational study. SETTING: Two PAH
      specialty treatment centers, Harbor-UCLA Medical Center (Torrance, CA), and the
      College of Physicians and Surgeons, Columbia University (New York, NY). PATIENTS:
      A total of 192 patients with PAH receiving continuous therapy with IV EPO.
      INTERVENTIONS: From 1987 to 2000, 192 patients with PAH received infusions of EPO
      via central venous catheter. Catheter care included regular dressing changes with
      dry gauze using a sterile procedure, without the use of flushes. Patients were
      asked to report on known infections and treatments, and symptoms. All infections
      were verified by a telephone call to the patient, care provider, and microbiology
      laboratory whenever possible. MEASUREMENTS AND RESULTS: There were 335,285
      catheter days (mean +/- SD, 1,325 +/- 974 catheter days). There were 88 clinical
      catheter infections with 51 blood culture-positive infections, necessitating
      catheter removal in 38 instances. The following pathogens were isolated:
      Staphylococcus aureus (25); Micrococcus spp (14); mixed flora (3); coagulase
      negative Staphylococcus spp (2); Corynebacterium spp (2); Serratia marcessens
      (1); Enterobacter spp (1); Pseudomonas aeruginosa (1); enterococci (1); and
      unidentified Gram-positive cocci (1). The catheter infection rate was 0.26 per
      1,000 catheter days. CONCLUSIONS: The use of long-term therapy with continuous
      EPO appears to be associated with a low incidence of catheter-related infections.
      Micrococcus spp were the second most common etiologic agent. Caregivers managing
      patients with PAH must be aware of the risk of catheter infection, as it may
      contribute to the morbidity and mortality associated with the use of EPO. When
      isolated, Micrococcus spp should not be viewed as a contaminant, but rather as a
      true pathogen that may require therapeutic intervention.

PMID- 15249448
TI  - Mannose-binding lectin gene polymorphism is a modulating factor in repeated
      respiratory infections.
AB  - STUDY OBJECTIVE: To clarify how mannose-binding lectin (MBL) participates in the
      pulmonary defense system. DESIGN: Multicenter retrospective study. PARTICIPANTS:
      Sixty-two patients with unexplained recurrent respiratory infections, 50 patients
      with nontuberculous mycobacterial infection, 23 patients with aspergillosis, and
      49 patients with diffuse panbronchiolitis (DPB). For controls, 52 blood samples
      were provided by the Blood Donation Center of the Japanese Red Cross Society. For
      BAL fluid (BALF) evaluation, there were five patients with acute phase pneumonia
      and five healthy volunteers. MEASUREMENT AND RESULTS: We demonstrated that MBL
      protein could be directly measured in the BALF from the lungs of patients with
      pneumonia by means of enzyme-linked immunosorbent assay. Furthermore, we
      demonstrated that the prevalence of the codon 54 mutation of the MBL gene in 62
      patients having repeated respiratory infections was significantly higher compared
      with healthy control subjects (54.8% vs 32.7%). The prevalence of the MBL mutant
      genotype among patients with DPB was higher (51.1%) than in the rest of the
      patients. In contrast, the prevalence of the MBL mutant genotype among patients
      with nontuberculous mycobacteria or Aspergillus chronic infection was not
      significantly different from that in control subjects (44.0% and 34.8%).
      CONCLUSIONS: Our results suggest that MBL may play an important role in
      modulating the inflammatory response against repeated microbial infections.

PMID- 15249449
TI  - Limited impact of a multicenter intervention to improve the quality and
      efficiency of pneumonia care.
AB  - STUDY OBJECTIVES: To evaluate the impact of a multifactorial intervention to
      improve the quality, efficiency, and patient understanding of care for community
      acquired pneumonia. DESIGN: Times series cohort study. SETTING: Four academic
      health centers in the New York City metropolitan area. PATIENTS OR PARTICIPANTS:
      All consecutive adults hospitalized for pneumonia during a 5-month period before
      (n = 1,013) and after (n = 1,081) implementation of an inpatient quality
      improvement (QI) initiative. INTERVENTIONS: A multidisciplinary team of opinion
      leaders developed evidence-based treatment guidelines and critical pathways,
      conducted educational sessions with physicians, distributed pocket reminder
      cards, promoted standardized orders, and developed bilingual patient education
      materials. MEASUREMENTS AND RESULTS: The average age was 71.4 years, and 44.1% of
      cases were low risk, 36.8% were moderate risk, and 19.2% were high risk. The
      preintervention and postintervention groups were well matched on age, sex, race,
      nursing home residence, pneumonia severity, initial presentation, and most major
      comorbidities. The intervention increased the use of guideline-recommended
      antimicrobial therapy from 78.1 to 83.4% (p = 0.003). There was also a borderline
      decrease in the proportion of patients being discharged prior to becoming
      clinically stable, from 27.0 to 23.5% (p = 0.06). However, there were no
      improvements in the other targeted indicators, including time to first dose of
      antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral
      antibiotics, timely discharge, length of stay, or patient education outcomes.
      CONCLUSIONS: This real-world QI program was able to improve modestly on some
      quality indicators, but not effect resource use or patient knowledge of their
      disease. Changing physician and organizational behavior in academic health
      centers will require the development and implementation of more intensive, system
      oriented strategies.

PMID- 15249450
TI  - The natural history of radiographically occult bronchogenic squamous cell
      carcinoma: a retrospective study of overdiagnosis bias.
AB  - OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does
      not produce signs or symptoms before the patient dies from other causes. We
      sought to determine whether overdiagnosis bias is a factor when screening for
      squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi
      Population-Based Lung Cancer Screening Registry for high-risk patients who were
      seen between January 1, 1982 (when sputum cytology tests were added for men with
      long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture,
      Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test
      results that were positive for squamous cell carcinoma but had normal radiograph
      findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of
      whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5
      year). END POINTS: Five-year and 10-year survival rates from primary lung cancer
      in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients,
      15 (34%) remained asymptomatic. The survival rate due to primary lung cancer
      death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The
      survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years.
      Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer.
      CONCLUSION: Given that the two thirds of the untreated patients with squamous
      cell carcinoma of the bronchus died from lung cancer within 10 years,
      overdiagnosis bias does not appear to be a factor in screening for this disease.
      Thus, we recommend that patients with radiographically occult squamous cell
      carcinoma of the bronchus undergo tumor treatment after localization.

PMID- 15249451
TI  - Baseline findings of a randomized feasibility trial of lung cancer screening with
      spiral CT scan vs chest radiograph: the Lung Screening Study of the National
      Cancer Institute.
AB  - BACKGROUND: Low-radiation-dose spiral CT (LDCT) scanning is capable of detecting
      lung neoplasms in asymptomatic individuals. To determine whether such detection
      can reduce lung cancer mortality, a randomized controlled trial (RCT) of LDCT
      scanning is necessary. METHODS: The feasibility of conducting an RCT in
      asymptomatic individuals who are at high risk for lung cancer was explored in the
      Lung Screening Study (LSS), a 12-month special project of the ongoing Prostate,
      Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. During the fall of
      2000, six PLCO screening centers recruited a total of 3,318 heavy or long-term
      smokers who were not participants in the PLCO trial and randomized them to
      receive either a screening LDCT scan (1,660 participants) or screening
      posteroanterior view chest radiograph (CXR) [1,658 participants]. RESULTS: The
      screens were completed on 96% of subjects in the LDCT scan arm and 93% of
      subjects in the CXR arm. A total of 20.5% of screened subjects in the LDCT scan
      arm and 9.8% of those in the CXR arm had findings that were suspicious for lung
      cancer. Thirty lung cancers in subjects in the LDCT arm and 7 lung cancers in
      patients in the CXR arm were diagnosed following a positive screening result.
      Additional data from the LSS indicated that, among persons who were at elevated
      risk for lung cancer, CT scan use was not pervasive, interest in participating in
      an RCT of LDCT scanning was strong, and few subjects randomized to CXR either
      refused their examination or sought a CT scan after their study CXR.
      INTERPRETATION: The results of the LSS demonstrated convincingly the feasibility
      of an RCT of LDCT scanning in the United States.

PMID- 15249452
TI  - Real-time endobronchial ultrasound-guided transbronchial needle aspiration of
      mediastinal and hilar lymph nodes.
AB  - STUDY OBJECTIVES: Although various techniques are available for obtaining
      pathology specimens from the mediastinal lymph nodes, including conventional
      bronchoscopic transbronchial needle aspiration (TBNA), transesophageal
      ultrasonography-guided needle aspiration, and mediastinoscopy, there are
      limitations to these techniques, which include low yield, poor access, need for
      general anesthesia, or complications. To overcome these problems, we undertook
      the current study to evaluate the clinical utility of the newly developed
      ultrasound puncture bronchoscope to visualize and perform real-time TBNA of the
      mediastinal and hilar lymph nodes under direct endobronchial ultrasonography
      (EBUS) guidance. DESIGN: Prospective patient enrollment. SETTING: University
      teaching hospital. PATIENTS: From March 2002 to September 2003, 70 patients were
      included in the study. INTERVENTIONS: The new convex probe (CP) EBUS is
      integrated with a convex scanning probe on its tip with a separate working
      channel, thus permitting real-time EBUS-guided TBNA. The indications for CP-EBUS
      were the diagnosis of mediastinal and/or hilar lymphadenopathy for known or
      suspected malignancy. Lymph nodes and the surrounding vessels were first
      visualized with CP-EBUS using the Doppler mode. The dimensions of the lymph nodes
      were recorded, followed by real-time TBNA under direct EBUS guidance. Final
      diagnosis was based on cytology, surgical results, and/or clinical follow-up.
      RESULTS: All lymph nodes that were detected on the chest CT scan could be
      visualized using CP-EBUS. In 70 patients, CP-EBUS-guided TBNA was performed to
      obtain samples from mediastinal lymph nodes (58 nodes) and hilar lymph nodes (12
      nodes). The sensitivity, specificity, and accuracy of CP-EBUS-guided TBNA in
      distinguishing benign from malignant lymph nodes were 95.7%, 100%, and 97.1%,
      respectively. The procedure was uneventful, and there were no complications.
      CONCLUSIONS: Real-time CP-EBUS-guided TBNA of mediastinal and hilar lymph nodes
      is a novel approach that is safe and has a good diagnostic yield. This new
      ultrasound puncture bronchoscope has an excellent potential for assisting in safe
      and accurate diagnostic interventional bronchoscopy.

PMID- 15249453
TI  - Echogenic swirling pattern as a predictor of malignant pleural effusions in
      patients with malignancies.
AB  - OBJECTIVES: Chest ultrasonography is a useful diagnostic tool for the detection
      of pleural effusions of different etiologies. Our purpose was to determine
      whether the echogenic swirling pattern identifiable on real-time chest
      ultrasonographic images is a predictor of malignant pleural effusions in patients
      with malignancies. DESIGN: Medical records of patients undergoing chest
      ultrasonography in the Tri-Service General Hospital (Taiwan) between January 2000
      and December 2002 were reviewed retrospectively. Patients with an echogenic
      swirling pattern in the pleural effusion, or with malignant diseases associated
      with pleural effusions, whose pleural fluids had been examined cytologically or
      whose pleural tissues had been examined pathologically, were enrolled in this
      study (n = 140). Malignant pleural effusions were defined by the presence of
      malignant cells in the pleural fluid identified by thoracentesis or by pleural
      biopsy. The echogenic swirling pattern was defined as numerous echogenic floating
      particles within the pleural effusion, which swirled in response to respiratory
      movement or heartbeat. Correlation between malignant pleural effusions and the
      echogenic swirling pattern was compared in patients with an underlying malignant
      disease. RESULTS: In patients with underlying malignancies, malignant pleural
      effusions were diagnosed in 81.8% of patients with a positive echogenic swirling
      pattern and in 48% of those with no echogenic swirling pattern. The presence of
      echogenic swirling was significantly more predictive of malignant pleural
      effusions than was the absence of echogenic swirling (p < 0.01). CONCLUSIONS: The
      echogenic swirling pattern is a useful predictor of possible malignant pleural
      effusions, and may be a good marker for malignant pleural effusions in patients
      with underlying malignancies.

PMID- 15249454
TI  - Cytokine response to pulmonary thromboendarterectomy.
AB  - BACKGROUND: Pulmonary thromboendarterectomy (PTE) is an effective but challenging
      treatment for chronic thromboembolic pulmonary hypertension (CTEPH). PTE is
      associated with marked hemodynamic instability in the perioperative course,
      suggesting the involvement of circulating mediators. The aim of this study was to
      characterize the expression of proinflammatory and anti-inflammatory cytokines in
      patients undergoing PTE. METHODS: Fourteen patients with CTEPH (mean [+/- SD]
      pulmonary vascular resistance, 1,056 +/- 399 dyne.s.cm(-5)) underwent PTE using
      cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).
      Peripheral arterial blood samples were drawn prior to patients undergoing
      sternotomy, during CPB, before and after DHCA, and 0, 8, 16, 24, and 48 h after
      surgery. An enzyme-linked-immunosorbent assay was used to analyze the plasma
      levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Seven
      patients undergoing aortic arch replacement (ARCH) in DHCA served as a control
      group. RESULTS: Prior to and during PTE, the CTEPH patients exhibited elevated
      TNF-alpha levels, which decreased within the first 24 postoperative hours (p =
      0.02). There was no TNF-alpha release among patients in the ARCH group. IL-6
      levels were similar in both groups throughout the perioperative course. A
      profound anti-inflammatory response was observed in the PTE group, which was
      reflected by elevated IL-10 levels prior to surgery and a marked peak level
      immediately after surgery. A positive correlation was found between maximum
      vasopressor support and peak levels of IL-6 (r = 0.82) in the PTE patients.
      CONCLUSION: Heart failure due to CTEPH appears to generate a pronounced
      inflammatory response with the release of proinflammatory and anti-inflammatory
      cytokines. PTE results in the rapid normalization of preoperatively elevated TNF
      alpha levels. IL-6-mediated systemic inflammatory cascades may be involved in the
      regulation of peripheral vascular tone after PTE.

PMID- 15249455
TI  - Outcome analysis of cirrhotic patients undergoing chest tube placement.
AB  - OBJECTIVES: Patients with cirrhosis can acquire pulmonary conditions that may or
      may not be related to their illness. Although posing a greater risk for
      complications, chest tubes are sometimes placed as treatment for hepatic
      hydrothorax and other pulmonary conditions. The aim of this study was to analyze
      the outcomes of chest tube placement in cirrhotic patients. METHODS: A
      retrospective analysis was performed of 59 adults with cirrhosis undergoing chest
      tube placement. Variables that were investigated included reason for chest tube
      placement, complications developing while having the tube in place, and outcome.
      RESULTS: The 59 subjects were classified as having Child-Turcotte-Pugh (CTP)
      class A cirrhosis (n = 3), CTP class B cirrhosis (n = 31), and CTP class C
      cirrhosis (n = 25). Indications for having a chest tube placed were hepatic
      hydrothorax (n = 24), pneumothorax (n = 9), empyema (n = 8), video-assisted
      thoracoscopy (VAT) [n = 7], non-VAT (n = 5), and hemothorax (n = 3). The CTP
      class A subjects had their chest tubes removed without further complications
      early in the course, and were excluded from further statistical analysis. Twenty
      five subjects (42%) had significant pleural effusions requiring chest tube
      placement. Among the CTP class B and class C subjects, the median duration with
      chest tube in place was 5.0 days (range, 1 to 53 days). Serum total bilirubin
      levels, presence of portosystemic encephalopathy, and CTP C classification were
      predictors of mortality. Mortalities were seen in 5 of 31 CTP class B subjects
      (16%), and 10 of 25 CTP class C subjects (40%). The tubes were successfully
      removed in a total of 39 subjects (66%) with no further procedure. Forty-seven
      subjects (80%) acquired one or more of the following complications: renal
      dysfunction, electrolyte imbalances, and infection. CONCLUSIONS: When placed for
      all indications, chest tubes may be successfully removed in the majority of
      cirrhotic patients. However, a third of all patients still die with the chest
      tube still in place. Failure to remove the chest tube increases mortality in
      patients with increasing severity of liver disease.

PMID- 15249456
TI  - Correlation of high-resolution CT, symptoms, and pulmonary function in patients
      during recovery from severe acute respiratory syndrome.
AB  - STUDY OBJECTIVES: Little is known of the nature of the recovery period after
      severe acute respiratory syndrome (SARS) infection. We hypothesized that
      structural changes of the lung might correlate with symptoms and pulmonary
      function. To answer this question, we correlate findings of high-resolution CT
      (HRCT) with dyspnea scores and results of pulmonary function tests in patients
      during recovery from SARS. DESIGN: Retrospective follow-up cohort study. SETTING:
      University hospital. PATIENTS: Nineteen patients who recovered from SARS-related
      hospitalization. MEASUREMENTS: The study included HRCT scores (0 to 100), dyspnea
      scores (1 to 4), static and dynamic lung volumes, and diffusing capacity of the
      lung for carbon monoxide (DLCO). RESULTS: The interval between hospital discharge
      and HRCT study or functional assessment was 31.2 +/- 4.8 days (range, 25 to 38
      days) [mean +/- SD]. All patients had HRCT abnormalities and were assigned to two
      groups: ground-glass opacity (GGO) only (n = 7, 36.8%) and GGO with fibrosis
      (GGO+F) [n = 12, 63.2%]. Most patients (16 of 19, 84.2%) had no zonal
      predominance. HRCT scores correlated well with dyspnea scores (r = 0.78, p <
      0.01) and with a variety of pulmonary functional variables, with DLCO being the
      most significant (r = - 0.923, p < 0.001). Compared with the GGO group, the GGO+F
      group showed significantly lower FEV(1), FVC, total lung capacity, residual
      volume, and DLCO. CONCLUSIONS: HRCT findings correlate well with functional
      studies and clinical symptoms during recovery from SARS. Longer-term follow-up
      studies in a larger cohort of patients should be performed to investigate the
      clinical outcome of recovered SARS patients.

PMID- 15249457
TI  - Assessment of ventilation during the performance of elective endoscopic-guided
      percutaneous tracheostomy: clinical evaluation of a new method.
AB  - STUDY OBJECTIVES: To evaluate the feasibility of uninterrupted translaryngeal
      open ventilation delivered through a pediatric, uncuffed endotracheal tube during
      percutaneous endoscopic tracheostomy (PET). DESIGN AND SETTING: Prospective,
      observational clinical study in a six-bed ICU of a university hospital. PATIENTS:
      Forty consecutive adult patients requiring an elective tracheostomy.
      INTERVENTIONS: We employed the basic Ciaglia technique with multiple dilators (n
      = 10), a single dilator (n = 15), and the Fantoni method (n = 15). During PET,
      pressure-controlled ventilation was maintained through an uncuffed, 4-mm inner
      diameter pediatric tube. The fraction of inspired oxygen was 1.0. Ventilator
      settings were as follows: pressure-controlled ventilation, 40 cm H(2)O;
      respiratory rate, 25/min; inspiratory time, 1.2 s of inspiratory time
      (inspiratory/expiratory ratio, 1:1); and positive end-expiratory pressure, 0 cm
      H(2)O. MEASUREMENTS AND RESULTS: Measurements of arterial blood gas (ABG)
      tensions were obtained before the start of each tracheostomy and every 3 min
      during the procedure. An average of 8.28 +/- 2.28 ABG measurements were obtained
      from each patient (+/- SD). All patients were successfully assisted during
      performance of the tracheostomy, and no patient required ventilation through a
      cuffed endotracheal tube. The maximum increase in PaCO(2) was 8.49 +/- 5.50 mm
      Hg, and the maximum decrease in pH related to hypercarbia was 0.04 +/- 0.04. The
      PaO(2) increased in all patients (maximum change, 69.75 +/- 57.00 mm Hg; p <
      0.01), and no patient had desaturation during the procedure. CONCLUSIONS: The
      technique that we propose for airway management during PET was safe and
      effective. A mild increase in PaCO(2) was not associated with significant
      metabolic and hemodynamic consequences, and an adequate PaO(2) was maintained
      throughout the study.

PMID- 15249458
TI  - The use of noninvasive ventilation in acute respiratory failure at a tertiary
      care center.
AB  - OBJECTIVE: Financial constraints and bed limitations frequently prevent admission
      of ill patients to a critical care setting. We surveyed the use of treatment with
      noninvasive ventilation (NIV) in clinical practice by physicians in a tertiary
      care, university-based teaching hospital and compared our findings with published
      recommendations for the use of NIV. METHODS: Data were collected prospectively on
      all patients with acute respiratory failure (ARF) for whom NIV was ordered over a
      5-month period. The respiratory therapy department was responsible for
      administering NIV on written order by a physician. The respiratory therapist
      completed a survey form with patient tracking data for each initiation of NIV.
      The investigators then surveyed the clinical chart for clinical data. RESULTS:
      NIV was utilized for the treatment of ARF on 75 occasions during the 5-month
      period. Fourteen patients (18%) received NIV for a COPD exacerbation, and 61
      patients (82%) received it for respiratory failure of other etiologies. NIV was
      initiated in the emergency department in 32% of patients, in a critical care
      setting in 27% of patients, in a ward observation unit in 23% of patients, and on
      a general medical or surgical ward in 18% of patients. Arterial blood gases
      (ABGs) were measured on 68 occasions prior to the initiation of NIV, and 51
      patients had an ABG measurement within the first 6 h of treatment. The mean pH at
      baseline was 7.29, and 33% of patients had a baseline pH of < 7.25. Seven
      patients required endotracheal intubation (ETI) [13%], and there were 18 deaths
      (24%) with patients having do-not-resuscitate orders, accounting for 12 deaths.
      CONCLUSION: NIV is commonly used outside of a critical care setting. Our outcomes
      of ETI and death were similar to those cited in the literature despite less
      aggressive monitoring of these patients.

PMID- 15249459
TI  - Septic shock of early or late onset: does it matter?
AB  - STUDY OBJECTIVES: To determine possible differences in morbidity and mortality
      between early and late onset of septic shock in ICU patients. DESIGN: Systematic
      data collection. SETTING: Thirty-one-bed, mixed, medicosurgical ICU in a
      university hospital. PATIENTS: All 65 patients who acquired septic shock after
      admission to the ICU between February 1999 and April 2000. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Forty-one of the 65 patients presented with septic
      shock within 24 h of admission to the ICU (early septic shock [ESS]); the other
      21 patients acquired septic shock > 24 h after ICU admission (late septic shock
      [LSS]). Eleven patients had a second episode (7 patients in the ESS group, and 4
      patients in the LSS group), and 1 patient in the LSS group had a third episode of
      septic shock. Patients with ESS had higher APACHE (acute physiology and chronic
      health evaluation) II (mean +/- SD, 26 +/- 6 vs 20 +/- 6; p = 0.002) and
      sequential organ failure assessment (SOFA) scores (11 +/- 3 vs 7 +/- 3, p <
      0.001) on ICU admission, and a higher blood lactate concentration at the onset of
      shock (median 3.70 mEq/L; interquartile range, 2.6 to 6.6 mEq/L; vs median, 2.50
      mEq/L [interquartile range, 1.8 to 4.0 mEq/L], p = 0.03) than patients with LSS.
      However, the duration of septic shock (median, 42 h [interquartile range, 21 to
      97 h] vs median, 93 h [interquartile range, 32 to 241 h], p = 0.058) and the
      length of ICU stay after the onset of septic shock (median, 75 h; [interquartile
      range, 38 to 203 h] vs median, 321 h [interquartile range, 96 to 438 h], p =
      0.018), was shorter in patients with ESS than patients with LSS. The ICU
      mortality rate was 63% (26 patients) in the ESS group, and 88% (21 patients) in
      the LSS group (p = 0.071). At the onset of the first episode of shock, patients
      with ESS had higher SOFA scores (11 +/- 3 vs 9 +/- 3, p = 0.045), lower pH (7.24
      +/- 0.15 vs 7.33 +/- 0.12, p = 0.01), and were treated with higher doses of
      dopamine (median, 20 microg/kg/min [interquartile range, 14 to 20 microg/kg/min]
      vs median, 12 microg/kg/min [interquartile range, 8 to 20 microg/kg/min], p =
      0.028) than patients with LSS. CONCLUSIONS: Septic shock is more severe when of
      early onset, as reflected by more severe organ dysfunction, greater lactic
      acidosis, and higher vasopressor requirements, yet the outcome is better, as
      reflected by a shorter duration of the shock episode, shorter ICU stay, and
      slightly lower mortality rates. These differences may influence clinical trials
      of therapeutic agents for sepsis, and should be taken into account when analyzing
      the results.

PMID- 15249460
TI  - Ultrasonographic evaluation of liver/spleen movements and extubation outcome.
AB  - INTRODUCTION: The diaphragm plays a pivotal role in weaning and successful
      extubation. We hypothesized that ultrasonographic evaluation of the movements of
      the diaphragm by measuring liver/spleen displacement during spontaneous breathing
      trials is a good predictor for extubation outcome. PATIENTS AND METHODS: The
      studied subjects were intubated patients receiving mechanical ventilation who
      were scheduled to be extubated. The displacement of liver/spleen was measured by
      ultrasonography before extubation. The patients were classified into a success
      group (SG) or failure group according to the extubation outcome. The baseline
      data and organ displacements in these two groups were analyzed. The sensitivity
      and specificity for the mean organ displacements and weaning parameters to
      predict successful extubation were calculated. RESULTS: We included 55 patients,
      32 of whom (58%) were in the SG. The baseline data are similar for these two
      groups, but the mean values of liver and spleen displacements were higher in the
      SG. Using a cutoff value of 1.1 cm, the sensitivity and specificity to predict
      successful extubation were 84.4% and 82.6%, respectively, better than traditional
      weaning parameters in this study. CONCLUSION: The displacement of the
      liver/spleen, measured by ultrasonography, is a good predictor for extubation
      outcome.

PMID- 15249461
TI  - Respiratory syncytial virus causes increased bronchial epithelial permeability.
AB  - BACKGROUND: Respiratory syncytial virus (RSV)-induced diseases are mediated
      through active cytokines released during infection. We hypothesized that RSV
      infection causes bronchial epithelial monolayer permeability in vitro via
      induction of vascular endothelial growth factor (VEGF). METHODS: Human bronchial
      epithelial cells were infected with RSV. In some cultures, VEGF antibody was
      included to block VEGF response; in other cultures, palivizumab was added to
      block RSV infection. Permeability was assessed in real-time using electric cell
      substrate impedance sensing. VEGF release was assessed using enzyme-linked
      immunosorbent assay. Gap formation was assessed using live cell imaging. RESULTS:
      RSV-infected cells demonstrated a decrease in the resistance of the monolayer
      indicating an increase in permeability; this increase was blocked with VEGF
      specific antibody, and palivizumab. Intercellular gap formation developed in RSV
      infected epithelial monolayers. CONCLUSION: RSV increases permeability of the
      bronchial airway epithelial monolayer via VEGF induction.

PMID- 15249462
TI  - A new technique for endobronchial ultrasonography and comparison of two
      ultrasonic probes: analysis with a plot profile of the image analysis software
      NIH Image.
AB  - STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is currently the sole
      clinical method available for delineating the bronchial wall structure; however,
      the image resolution is inadequate. Thus, an improved image analysis system is
      needed for both a more accurate and more readily interpretable endobronchial
      ultrasonogram. MATERIALS AND METHODS: A total of 10 patients underwent pulmonary
      resection for lung cancer. EBUS was performed on the bronchi of the resected
      lungs, which had been immersed in physiologic saline solution. The same bronchial
      lesion in each specimen was imaged with two probes: 20 MHz and 30 MHz. The images
      were analyzed using the plot profile derived from freeware image analysis
      software: NIH Image (National Institutes of Health; Bethesda, MD). The measured
      echo intensity of the bronchial wall was statistically analyzed. RESULTS: A
      normal bronchial wall image consists of five layers, and the plot profile shows a
      W-shaped curve. The mean value of the echo intensity of each peak or trough of
      the W-shaped curve was calculated and compared for both probes. The differences
      in the mean echo intensity between both the third and fourth layer and the second
      and fourth layer were found to be significantly greater with the 30-MHz probe
      than with the 20-MHz probe. The echo intensity curve of a central-type lung
      cancer was not W shaped, indicating that the bronchial wall was not composed of
      the normal five layers. CONCLUSION: We employed image analysis software and drew
      a plot to obtain a W-shaped curve from the EBUS image data. This enabled us to
      make an objective assessment of the laminar structure of the bronchial wall. In
      order to clearly recognize the laminar structure of the bronchial wall, the 30
      MHz probe was found to be more useful than the 20-MHz probe.

PMID- 15249463
TI  - Effect of nitrogen dioxide exposure on allergic asthma in a murine model.
AB  - STUDY OBJECTIVES: The purpose of this study was to examine the effects of NO(2),
      a major component of air pollution, on airway eosinophilic inflammation and
      bronchial hyperreactivity, using a mouse model of asthma. SETTING AND SUBJECTS:
      BALB/c mice (eight mice per experimental group) were studied in a basic research
      laboratory at the University of Iowa. INTERVENTIONS: Using a standard murine
      model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) by
      intraperitoneal (IP) injections (days 1 and 7) and were challenged with
      aerosolized OVA (days 13 and 14). Some mice were exposed to NO(2) (2 ppm) in an
      exposure chamber for 24 h before undergoing OVA aerosol challenge. A control
      group was exposed to OVA alone. MEASUREMENTS AND RESULTS: The outcomes assessed
      included airway inflammation, bronchial hyperreactivity to inhaled methacholine,
      and goblet cell hyperplasia. We found that NO(2) exposure modestly increased
      airway neutrophilia but not airway eosinophilia in OVA-exposed mice. These mice
      exhibited epithelial damage and loss of epithelial mucin. Surprisingly,
      nonspecific bronchial hyperreactivity (ie, enhanced pause index) was not
      increased, although baseline smooth muscle tone was increased (p < 0.05) in the
      mice exposed to NO(2). CONCLUSIONS: These data indicate that relatively short
      term (24 h) exposure to NO(2) causes epithelial damage, reduced mucin expression,
      and increased tone of respiratory smooth muscle. Reduced mucin production may be
      a mechanism of injury following long-term exposure to inhaled NO(2). Despite
      enhancing epithelial damage in OVA-exposed mice, NO(2) exposure does not
      otherwise alter the expression of allergen-induced airway responses.

PMID- 15249464
TI  - Airway mucosal thickening and bronchial hyperresponsiveness induced by inhaled
      beta 2-agonist in mice.
AB  - BACKGROUND: Patients with chronic persistent asthma require frequent use of
      inhaled beta(2)-agonist, which may result in aggravation of asthma symptoms. Our
      recent in vitro study has shown that beta(2)-agonist stimulates the growth of
      human airway epithelial cell lines. STUDY OBJECTIVE: To determine whether beta(2)
      agonist likewise affects airway epithelial cell proliferation in vivo and, if so,
      what the mechanism of action is, we examined the effect of salbutamol on the
      morphology of murine airways. METHODS: Seventy-two BALB/c mice were administered
      aerosolized salbutamol using "flow-through" nose-only inhalation chambers at
      daily doses of 0.2 to 20 microg for up to 6 weeks. Morphology of tracheal mucosa,
      labeling of epithelial cells with 5-bromo-2'-deoxyuridine (BrdU), and bronchial
      responsiveness were assessed. RESULTS: Exposure to salbutamol increased the
      thickness of tracheal epithelial layer and the number of BrdU-positive epithelial
      cells in a dose- and time-dependent manner: the values in mice receiving 20
      microg salbutamol for 6 weeks were 247% and 642%, respectively, of those in
      control animals receiving saline solution alone. These effects were inhibited by
      the mitogen-activated protein (MAP) kinase kinase inhibitors PD98059 and U0126.
      Salbutamol also caused a decrease in the provocative concentration of
      methacholine to achieve 400% of baseline enhanced pause. Combined treatment with
      inhaled budesonide attenuated salbutamol-induced airway morphologic changes and
      bronchial hyperresponsiveness. CONCLUSION: beta(2)-agonist stimulates
      proliferation of airway epithelial cells and produces airway wall thickening in
      vivo via MAP kinase-dependent pathway, and these effects are prevented by inhaled
      corticosteroid.

PMID- 15249465
TI  - The local side effects of inhaled corticosteroids: current understanding and
      review of the literature.
AB  - The frequent use of inhaled corticosteroids (ICSs), especially at higher doses,
      has been accompanied by concern about both systemic and local side effects. The
      systemic complications of ICSs have been extensively studied and are well
      documented in the literature. There are comparatively few studies reporting on
      the local complications of ICSs. Compared with systemic side effects, the local
      side effects of ICSs are considered to constitute infrequent and minor problems.
      However, while not usually serious, these local side effects are of clinical
      importance. They may hamper compliance with therapy and the symptoms produced may
      mimic more sinister pathology. This review considers the prevalence of local side
      effects, their clinical features, the potential causes, the role of inhaler
      devices, and current measures that have been suggested to avoid the problem.

PMID- 15249466
TI  - Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids
      in stable COPD.
AB  - Long-acting beta(2)-agonists (LABAs) have been shown to be effective first-line
      bronchodilators in the treatment of COPD patients, and inhaled corticosteroids
      (ICSs) have been shown to reduce the frequency and/or severity of exacerbations
      in COPD patients. The concomitant use of a LABA and an ICS can influence both
      airway obstruction (ie, smooth muscle contraction, increased cholinergic tone,
      and loss of elastic recoil), and airway inflammation (ie, increased numbers of
      neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor
      necrosis factor-alpha levels, and protease/antiprotease imbalance). They are also
      able to reduce the total number of bacteria adhering to the respiratory mucosa in
      a concentration-dependent manner without altering the bacterial tropism for
      mucosa, and to preserve ciliated cells. Several clinical trials support the
      concept of inhaled combination therapy with LABAs and corticosteroids in stable
      COPD patients. This type of therapy not only improves airflow obstruction but
      also provides clinical benefits, as manifested by sustained reduction in overall
      symptoms, improvements in health-related quality of life, and reductions in
      exacerbations. All of these effects are very important because, despite recent
      advances in our understanding of COPD and its treatment, therapy remains
      suboptimal for a considerable number of patients.

PMID- 15249467
TI  - Innovative approaches to lung volume reduction for emphysema.
AB  - The 10 years of resurgent interest in lung volume reduction surgery (LVRS) and
      recent National Emphysema Treatment Trial findings for emphysema have stimulated
      a range of innovative alternative ideas aimed at improving outcomes and reducing
      complications associated with current LVRS techniques. Concepts being actively
      investigated at this time include surgical resection with compression/banding
      devices, endobronchial blockers, sealants, obstructing devices and valves, and
      bronchial bypass methods. These novel approaches are reaching the stage of
      clinical trials at this time. Theory, design issues, methods, potential
      advantages and limitations, and available results are presented. Extensive
      research in the near future will help to determine the potential clinical
      applicability of these new approaches to the treatment of emphysema symptoms.

PMID- 15249468
TI  - Transfusion-related acute lung injury: a review.
AB  - Transfusion-related acute lung injury (TRALI) is an underreported complication of
      transfusion therapy, and it is the third most common cause of transfusion
      associated death. TRALI is defined as noncardiogenic pulmonary edema temporally
      related to transfusion therapy. The diagnosis of TRALI relies on excluding other
      diagnoses such as sepsis, volume overload, and cardiogenic pulmonary edema.
      Supportive diagnostic evidence includes identifying neutrophil or human leukocyte
      antigen (HLA) antibodies in the donor or recipient plasma. All plasma-containing
      blood products have been implicated in TRALI, with the majority of cases linked
      to whole blood, packed RBCs, platelets, and fresh-frozen plasma. The pathogenesis
      of TRALI may be explained by a "two-hit" hypothesis, with the first "hit" being a
      predisposing inflammatory condition commonly present in the operating room or
      ICU. The second hit may involve the passive transfer of neutrophil or HLA
      antibodies from the donor or the transfusion of biologically active lipids from
      older, cellular blood products. Treatment is supportive, with a prognosis
      substantially better than most causes of clinical acute lung injury.

PMID- 15249469
TI  - Transbronchial needle aspiration in diagnosing intrathoracic tuberculous
      lymphadenitis.
AB  - STUDY OBJECTIVE: To assess the role of transbronchial needle aspiration (TBNA) in
      diagnosing intrathoracic tuberculous lymphadenitis (TB-LA). METHODS: In a
      tertiary referral center for thoracic medicine and surgery, using a CT scan as a
      guide, transbronchial aspirates were obtained with a 19-gauge flexible histology
      needle in consecutively enrolled patients with sputum smears negative for acid
      fast bacilli, and with isolated mediastinal or hilar adenopathy suspicious for
      tuberculosis (TB). RESULTS: Of 84 eligible patients who were all found to be HIV
      negative, 63 (75%) cases of TB were diagnosed by TBNA (histology, 48 patients
      [76%]; cytology, 9 patients [14%]; and bacteriologic studies, 21 patients [33%;
      smear, 8 patients; culture, 17 patients]). TBNA was used to diagnose sarcoidosis
      in two patients, angioimmunoblastic lymphadenopathy in one patient, and Hodgkin
      lymphoma in one patient. In the 17 TBNA-negative patients, the results of
      transthoracic needle aspiration were positive in 12 patients (TB, nine patients;
      lung cancer, two patients; sarcoidosis, one patient), the results of
      mediastinoscopy were positive in three patients (TB, two patients; Hodgkin
      lymphoma, one patient), and the results of thoracotomy were positive in two
      patients (TB, two patients). Thus, 76 patients had TB, and all responded to anti
      TB treatment. TB was corroborated by culture or histology of another specimen
      obtained from subsequently developed lesions in 40 patients (53%) during anti-TB
      treatment or posttreatment follow-up. TBNA was immediately diagnostic in 59
      patients (78%), and exclusively in 52 patients (68%), among all bronchoscopic
      procedures and prebronchoscopic sputum studies. Sensitivity, specificity,
      positive and negative predictive values, and accuracy of TBNA for TB were 83%,
      100%, 100%, 38%, and 85%, respectively. The only complication, self-limiting
      hemorrhage of < 30 mL volume, occurred in 65 patients (77%), with a volume of < 5
      mL in 59 patients (70%). CONCLUSION: TBNA is efficient and safe in the
      bacteriologic and pathologic diagnosis of intrathoracic TB-LA in HIV-negative and
      sputum smear-negative patients.

PMID- 15249470
TI  - The clinical utility of flexible bronchoscopy in the evaluation of chronic cough.
AB  - STUDY OBJECTIVES: To assess the clinical utility of flexible bronchoscopy (FB) in
      the evaluation of patients with chronic cough and normal or nonlocalizing chest
      radiographic findings. DESIGN: Retrospective chart review. SETTING: Tertiary
      referral center. PATIENTS: Forty-eight patients with chronic cough and no other
      clinical or radiographic indications for FB who underwent the procedure from 1996
      to 2001. RESULTS: Before FB, 45 patients had a chest radiograph and 21 patients
      had a chest CT performed. On visual inspection, 37 of 48 of the FB findings (82%)
      were normal, 9 were consistent with "bronchitis," one patient had a "small
      tracheal plaque," and one patient had "minimal arytentoid redundancy." Three of
      the 27 patients who had a microbiologic assessment performed during their FB
      demonstrated potentially pathogenic organisms. Antibiotic treatment based on
      culture data did not result in improvement in cough. Cytologic examination was
      performed in specimens from 33 patients; 1 patient was noted to have reactive
      squamous atypia, and the remainder were normal. The patient noted to have minimal
      arytenoid redundancy and the patient with a tracheal plaque each had another
      etiology for their cough identified, the treatment of which resulted in cough
      improvement. CONCLUSIONS: FB adds little to the diagnosis of chronic cough in the
      context of normal or nonlocalizing chest radiographic or CT findings. FB did not
      result in successful treatment alteration, nor did it contribute to the
      identification of the cough etiology.

PMID- 15249471
TI  - Role of transbronchial biopsies in pediatric lung diseases.
AB  - STUDY OBJECTIVE: To evaluate the role of transbronchial biopsies (TBBs) in
      pediatric lung diseases. DESIGN AND METHODS: We reviewed the records of TBBs
      performed in pediatric patients at the University of Florida between July 1996
      and August 2003. The sample adequacy, diagnostic utility, and procedural
      complications of the two types of bronchoscopy apparatuses used to collect the
      samples were assessed and compared. PATIENTS: A total of 429 TBB procedures were
      performed in 46 patients (age range, 2 months to 21 years) who had received a
      heart-lung or lung transplant and in 38 non-lung transplant patients (age range,
      2 weeks to 18 years). For 86 procedures, the pediatric bronchoscope and forceps
      that fit in a 1.2-mm channel were used, and a small adult bronchoscope and 2.0-mm
      forceps were used for the remaining procedures. RESULTS: Adequate tissue samples
      were obtained in 85% of the procedures using a pediatric bronchoscope and in 97%
      using an adult bronchoscope. In the non-lung transplant patients, the biopsy
      findings were considered to be diagnostic in 58% of all procedures (adult
      bronchoscope, 64%; and pediatric bronchoscope, 50%), contributory in 21%, and
      noncontributory in 21%. In the lung transplant patients, treatable acute cellular
      rejection was diagnosed in 24% of the surveillance TBBs and in 47% of the TBBs
      performed as a result of clinical symptoms. Complications included five
      pneumothoraces and five episodes of excessive bleeding requiring the
      discontinuation of the procedure in three of the cases. CONCLUSIONS: Adequate
      lung tissue for histologic diagnosis can be obtained safely and effectively from
      pediatric patients of all ages via flexible bronchoscopy with TBB. The
      performance of bronchoscopy should be considered based on clinical indications,
      rather than on the age or size of the patient, when a tissue diagnosis is needed.
      When feasible, the use of an adult bronchoscope is preferable due to the higher
      diagnostic yield.

PMID- 15249472
TI  - Video-assisted thoracoscopic surgery using single-lumen endotracheal tube
      anesthesia.
AB  - BACKGROUND: Most general thoracic surgeons use double-lumen endotracheal tube
      (DLET) anesthesia for all video-assisted thoracoscopic surgery (VATS). We
      evaluated a single-lumen endotracheal tube (SLET) for VATS for drainage of
      pleural effusions and pleural biopsies. METHODS: A consecutive series of patients
      with recurrent pleural effusions underwent VATS using an SLET and only one
      incision. Operations were accomplished via one 2-cm incision using a 5-mm rigid
      thoracoscope and mediastinoscopic biopsy forceps for directed pleural biopsies. A
      working area was accomplished with low tidal volumes. RESULTS: There were 376
      patients (191 women). The indications for VATS were a nondiagnosed or benign
      pleural effusion in 294 patients, and a malignant effusion in 82 patients. Two
      hundred eight patients underwent biopsy of the parietal pleura, and mean
      operative time was 17 min. Adequate visibility was obtained in all. When compared
      to preoperative cytology, VATS was more sensitive (45% compared to 99%, p <
      0.001), had a higher negative predictive value (56% compared to 99%, p < 0.001),
      and was more accurate (67% compared to 99%, p < 0.001). Forty-seven percent of
      patients with a history of cancer had false-negative preoperative cytology
      results. Complications occurred in seven patients (2%), and there were three
      operative deaths (none related to the operative procedure). CONCLUSION: VATS
      using SLET and only one incision is possible, and it affords excellent
      visualization of the pleural space, allowing pleural biopsies and talc
      insufflation. It avoids the risk, time, and cost of a DLET. It is significantly
      more sensitive and accurate than preoperative cytology, and it should be
      considered as the diagnostic and therapeutic procedure of choice in patients with
      recurrent pleural effusions.

PMID- 15249473
TI  - Narcotic and benzodiazepine use after withdrawal of life support: association
      with time to death?
AB  - OBJECTIVE: To determine whether the dose of narcotics and benzodiazepines is
      associated with length of time from mechanical ventilation withdrawal to death in
      the setting of withdrawal of life-sustaining treatment in the ICU. DESIGN:
      Retrospective chart review. SETTING: University-affiliated, level I trauma
      center. PATIENTS: Consecutive critically ill patients who had mechanical
      ventilation withdrawn and subsequently died in the ICU during two study time
      periods. RESULTS: There were 75 eligible patients with a mean age of 59 years.
      The primary ICU admission diagnoses included intracranial hemorrhage (37%),
      trauma (27%), acute respiratory failure (27%), and acute renal failure (20%).
      Patients died during a median of 35 min (range, 1 to 890 min) after ventilator
      withdrawal. On average, 16.2 mg/h opiates in morphine equivalents and 7.5 mg/h
      benzodiazepine in lorazepam equivalents were administered during the time period
      starting 1 h before ventilator withdrawal and ending at death. There was no
      statistically significant relationship between the average hourly narcotic and
      benzodiazepine use during the 1-h period prior to ventilator withdrawal until
      death, and the time from ventilator withdrawal to death. The restriction of
      medication assessment in the last 2 h of life showed an inverse association
      between the use of benzodiazepines and time to death. For every 1 mg/h increase
      in benzodiazepine use, time to death was increased by 13 min (p = 0.015). There
      was no relationship between narcotic dose and time to death during the last 2 h
      of life (p = 0.11). CONCLUSIONS: We found no evidence that the use of narcotics
      or benzodiazepines to treat discomfort after the withdrawal of life support
      hastens death in critically ill patients at our center. Clinicians should strive
      to control patient symptoms in this setting and should document the rationale for
      escalating drug doses.

PMID- 15249474
TI  - A 73-year-old man with chest pain 4 days after a fish dinner.

PMID- 15249475
TI  - A new radiologic appearance of pulmonary thromboembolism: multiloculated pleural
      effusions.
AB  - The objective of this study was to describe the clinical course and response to
      treatment of five patients who developed loculated pleural effusions as
      complications of pulmonary thromboembolism (PTE). The clinical charts of five
      patients who had loculated pleural effusions in the course of their PTE were
      reviewed, with special attention paid to the duration of symptoms before
      diagnosis, the pleural fluid analysis findings, and the response of the
      loculations to anticoagulant therapy. In a tertiary care academic medical center,
      the five patients described in the present study had multiple locules of pleural
      fluid seen on chest radiographs and thoracic CT scans. In all cases, the
      diagnosis of PTE had been delayed for at least 2 weeks after symptoms developed.
      The loculated pleural fluid had led to the mistaken diagnosis of empyema in three
      cases. The pleural fluid in all cases was exudative, with a predominance of
      lymphocytes. With anticoagulant therapy, the loculations largely disappeared
      within the first few days of therapy. Although most pleural effusions secondary
      to PTE are relatively small and free-flowing, this study demonstrates that PTE
      can lead to loculated pleural effusions. The loculations occurred in patients who
      had been symptomatic from their PTE for > 2 weeks. In each instance, the pleural
      fluid was a lymphocytic exudate. The effusions rapidly resolved with the
      institution of anticoagulant therapy. PTE should be included in the differential
      diagnosis of a loculated pleural effusion, particularly if the pleural fluid
      contains predominantly lymphocytes.

PMID- 15249476
TI  - Nesiritide in pulmonary hypertension.
AB  - We present the case of a patient with severe symptomatic pulmonary hypertension
      due to rheumatic mitral valve disease who was refractory to traditional
      therapies, including prostacyclin. Therapy with continuous nesiritide infusion
      resulted in significant and sustained decreases in pulmonary vascular resistance,
      an improvement in renal function, and the maintenance of euvolemia.

PMID- 15249477
TI  - Use of extracorporeal membrane oxygenation in a patient with diffuse alveolar
      hemorrhage.
AB  - Extracorporeal membrane oxygenation (ECMO) was developed as a supportive therapy
      for severe respiratory failure. It has been shown to be life-saving in neonates
      and children with isolated respiratory failure, however, its usefulness in adults
      remains controversial. We report the successful use of ECMO in an adult patient
      with severe hypoxemic respiratory failure secondary to diffuse alveolar
      hemorrhage from Wegener granulomatosis.

PMID- 15249478
TI  - Stage IA lung cancer size and survival.

PMID- 15249479
TI  - Hydroxyethyl starch-induced postoperative bleeding in cardiac surgery patients:
      more trials needed?

PMID- 15249480
TI  - Cardiogenic shock.

PMID- 15249481
TI  - P wave in pulmonary impairment.

PMID- 15249482
TI  - Linezolid and vancomycin for methicillin-resistant Staphylococcus aureus
      nosocomial pneumonia: the subtleties of subgroup analyses.

PMID- 15249483
TI  - Nasal airflow in sleep-disordered breathing.

PMID- 15249484
TI  - Treatment of a primary pulmonary angiosarcoma.

PMID- 15249485
TI  - Airway hyperresponsiveness to bronchial mannitol: where do we go from here?

PMID- 15249486
TI  - Antibiotic administration in community-acquired pneumonia.

PMID- 15249487
TI  - Anti-inflammatory Effect of Pentoxifylline.

PMID- 15249490
TI  - Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based
      clinical practice guidelines.

PMID- 15249491
TI  - Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based
      clinical practice guidelines.

PMID- 15249492
TI  - Methodology and grading for pulmonary hypertension evidence review and guideline
      development.
AB  - The American College of Chest Physicians assembled a multidisciplinary,
      geographically diverse panel of experts in the treatment of pulmonary
      hypertension to develop clinically relevant practice guidelines for the diagnosis
      and treatment of pulmonary hypertension in its many variations. That group of
      experts produced recommendations covering five topic areas, each related to a
      distinct set of patient-management decisions. This article describes the approach
      used to develop the guidelines, including identifying, evaluating, and
      synthesizing the evidence, assessing the strength of evidence pertinent to
      individual guidelines, and grading guideline recommendations.

PMID- 15249493
TI  - Screening, early detection, and diagnosis of pulmonary arterial hypertension:
      ACCP evidence-based clinical practice guidelines.
AB  - Pulmonary arterial hypertension (PAH) occurs as an idiopathic process or as a
      component of a variety of disease processes, including chronic thromboembolic
      disease, connective tissue diseases, congenital heart disease, and exposure to
      exogenous factors including appetite suppressants or infectious agents such as
      HIV. This article reviews evidence for screening in susceptible patient groups
      and the approach to diagnosing PAH when it is suspected, and provides specific
      recommendations for applying this evidence to clinical practice.

PMID- 15249494
TI  - Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical
      practice guidelines.
AB  - Pulmonary arterial hypertension (PAH) is often difficult to diagnose and
      challenging to treat. Untreated, it is characterized by a progressive increase in
      pulmonary vascular resistance leading to right ventricular failure and death. The
      past decade has seen remarkable improvements in therapy, driven largely by the
      conduct of randomized controlled trials. Still, the selection of most appropriate
      therapy is complex, and requires familiarity with the disease process, evidence
      from treatment trials, complicated drug delivery systems, dosing regimens, side
      effects, and complications. This chapter will provide evidence-based treatment
      recommendations for physicians involved in the care of these complex patients.
      Due to the complexity of the diagnostic evaluation required, and the treatment
      options available, it is strongly recommended that consideration be given to
      referral of patients with PAH to a specialized center.

PMID- 15249495
TI  - Surgical treatments/interventions for pulmonary arterial hypertension: ACCP
      evidence-based clinical practice guidelines.
AB  - While considerable advances have been achieved in the medical treatment of
      pulmonary arterial hypertension (PAH) over the past decade, surgical and
      interventional approaches continue to have important roles in those patients for
      whom medical therapy is unavailable or has been unsuccessful. These techniques
      include pulmonary thromboendarterectomy for chronic thromboembolic pulmonary
      hypertension, thoracic transplantation, and atrial septostomy. This chapter will
      provide evidence-based recommendations for the selection and timing of surgical
      and interventional treatments of PAH for physicians involved in the care of these
      complex patients.

PMID- 15249496
TI  - Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based
      clinical practice guidelines.
AB  - The objective of this article is to review the available data on the relationship
      between sleep-disordered breathing (SDB) and pulmonary arterial hypertension
      (PAH), with a focus on the prevalence of SDB in patients with idiopathic PAH
      (IPAH); the prevalence of PAH in patients with SDB; and the effects of SDB
      treatment on PAH. The evidence to date suggests that PAH may occur in the setting
      of SDB, although the prevalence is low. However, pulmonary hypertension (PH) in
      SDB is most strongly associated with other risk factors, such as left-sided heart
      disease, parenchymal lung disease, nocturnal desaturation, and obesity. The
      limited data available also suggest that SDB is uncommon in patients with IPAH.
      Treatment of SDB with continuous positive airway pressure may lower pulmonary
      artery pressures when the degree of PH is mild.

PMID- 15249497
TI  - Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical
      practice guidelines.
AB  - Although idiopathic pulmonary arterial hypertension is perceived as a progressive
      disease with a uniformly poor outcome, the natural history of disease is
      heterogeneous, with some patients dying within months of diagnosis and others
      living for decades. The course of the disease has also been altered by advances
      in medical therapies. The outcome of patients with other types of pulmonary
      arterial hypertension (PAH) has been less well characterized. Assessment of
      prognosis of such patients is important, as it influences both medical therapy
      and referral for transplantation. This chapter will provide evidence based
      recommendations to assess the prognosis of patients with PAH.

PMID- 15249498
TI  - Anti-Xa activity relates to survival and efficacy in unselected acute coronary
      syndrome patients treated with enoxaparin.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) is recommended in the treatment
      of unstable angina (UA)/non-ST-segment-elevation myocardial infarction (NSTEMI),
      but no relationship has ever been shown between anticoagulation levels obtained
      with LMWH treatment and clinical outcomes. METHODS AND RESULTS: In all, 803
      consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and
      were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID
      was used throughout the population except when physicians decided on dose
      reduction because of a history of a recent bleeding event or because of a high
      bleeding risk. Anti-factor Xa activity was >0.5 IU/mL in 93% of patients;
      subtherapeutic anti-Xa levels (<0.5 IU/mL) were associated with lower doses of
      enoxaparin. The 30-day mortality rate was significantly associated with low anti
      Xa levels (<0.5 IU/mL), with a >3-fold increase in mortality compared with the
      patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL (P=0.004).
      Multivariate analysis revealed low anti-Xa activity as an independent predictor
      of 30-day mortality at least as strong as age, left ventricular function, and
      renal function. In contrast, anti-Xa activity did not predict major bleeding
      complications within the range of anti-Xa levels observed in this study.
      CONCLUSIONS: In this large unselected cohort of patients with UA/NSTEMI patients,
      low anti-Xa activity on enoxaparin treatment is independently associated with 30
      day mortality, which highlights the need for achieving at least the minimum
      prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.

PMID- 15249499
TI  - Association of anti-heat shock protein 65 antibodies with development of
      postoperative atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is a frequently encountered arrhythmia after
      cardiac surgery, but its underlying mechanisms are still unclear. We hypothesize
      that autoimmune and inflammatory responses against heat shock protein 65 (HSP65)
      may be involved and hence examined the relationship between HSP65 autoantibodies
      and occurrence of postoperative AF. METHODS AND RESULTS: A prospective study of
      329 patients undergoing elective primary CABG was undertaken. Cardiovascular risk
      factors, ECG characteristics, medications, and intraoperative and postoperative
      features were documented. Anti-HSP65 antibodies and C-reactive protein levels
      were measured in all preoperative blood samples with ELISA. Postoperative AF was
      defined as the characteristic arrhythmia, lasting for at least 15 minutes and
      confirmed on 12-lead ECG and occurring within the first postoperative week. This
      occurred in 62 patients (19%). In univariate analysis, HSP65 antibodies were
      significantly higher in patients with postoperative AF (P=0.02). History of
      previous myocardial infarction, duration of bypass, number of distal anastomosis,
      and duration of ventilation were also associated with AF (P<0.05), but C-reactive
      protein levels were not (P=0.13). Multivariate analysis confirmed the positive
      association of HSP65 antibodies with postoperative AF (OR, 1.41; P=0.04)
      independent of age, sex, other cardiovascular risk factors, severity of coronary
      artery disease, duration of ventilation, duration of bypass, and left ventricular
      function. CONCLUSIONS: We report a novel association between anti-HSP65
      antibodies and occurrence of postoperative AF, indicating a possible role for
      antibody-mediated immune response in its pathogenesis.

PMID- 15249500
TI  - Protective role for interferon-beta in coxsackievirus B3 infection.
AB  - BACKGROUND: Coxsackievirus-induced myocarditis can be a serious cause of heart
      failure. In the absence of a specific antiviral therapy, modulating the host
      immune response may be protective. Interferons (IFNs)-alpha and -beta perform a
      fundamental role in innate and adaptive antiviral responses, thereby presenting
      as candidate therapeutics for coxsackievirus infections. METHODS AND RESULTS: To
      examine the contribution of IFN-beta in protection from coxsackievirus B3 (CVB3)
      infection, mice lacking the IFN-beta gene were infected with 10(3) plaque-forming
      units of CVB3. In contrast to wild-type mice that exhibit an intact IFN-beta
      response, we observed increased susceptibility to infection (70% mortality), a
      downregulation of IFN-stimulated gene targets (2'-5' oligoadenylate synthetase,
      serine/threonine protein kinase, the GTPase Mx), and cardiomyocyte breakdown and
      disruption in the IFN-beta-/- mice. CONCLUSIONS: Viewed together, these results
      clearly demonstrate that IFN-beta is important in mediating protection against
      CVB3-induced myocarditis.

PMID- 15249501
TI  - Identification by a differential proteomic approach of heat shock protein 27 as a
      potential marker of atherosclerosis.
AB  - BACKGROUND: We hypothesized that normal and pathological vessel walls display a
      differential pattern of secreted proteins. We have recently set up the conditions
      for comparing secretomes from carotid atherosclerotic plaques and control
      arteries using a proteomic approach to assess whether differentially secreted
      proteins could represent markers for atherosclerosis. METHODS AND RESULTS: Normal
      endartery segments and different regions of endarterectomy pieces
      (noncomplicated/complicated plaques) were incubated in protein-free medium, and
      the released proteins were analyzed by 2D electrophoresis (2-DE). Among the
      differently secreted proteins, we have identified heat shock protein-27 (HSP27).
      Surprisingly, compared with control arteries, HSP27 release was drastically
      decreased in atherosclerotic plaques and barely detectable in complicated plaque
      supernatants. HSP27 was expressed primarily by intact vascular cells of normal
      arteries and carotid plaques (immunohistochemistry). Plasma detection of soluble
      HSP27 showed that circulating HSP27 levels are significantly decreased in the
      blood of patients with carotid stenosis relative to healthy subjects (0.19 [0.1
      to 1.95] versus 83 [71.8 to 87.8]) ng/mL, P<0.0001). CONCLUSIONS: HSP27 secretion
      is decreased in complicated atherosclerotic plaques, and sHSP27 plasma levels are
      decreased in atherosclerotic patients compared with healthy subjects. Plasma
      sHSP27 levels could be a potential index of atherosclerosis, although further
      validation is needed in large patient cohorts.

PMID- 15249502
TI  - CD34+ and endothelial progenitor cells in patients with various degrees of
      congestive heart failure.
AB  - BACKGROUND: Peripheral blood CD34(+) cells and circulating endothelial progenitor
      cells (EPCs) increase in myocardial infarction and vascular injuries as a
      reflection of endothelial damage. Despite the occurrence of endothelial
      dysfunction in heart failure (HF), no data are available on EPC mobilization in
      this setting. We investigated the pattern of CD34(+) cells and EPC mobilization
      during HF and their correlation with the severity and origin of the disease.
      METHODS AND RESULTS: Peripheral blood CD34(+) cells (n=91) and EPCs (n=41),
      assessed both as CD34(+) cells coexpressing AC133 and vascular endothelial growth
      factor (VEGF) receptor-2 and as endothelial colony-forming units, were studied in
      HF patients (mean age 67+/-11 years) and 45 gender- and age-matched controls.
      Tumor necrosis factor-alpha (TNF-alpha) and its receptors (sTNFR-1 and sTNFR-2),
      VEGF, stromal derived factor-1 (SDF-1), granulocyte-colony stimulating factor (G
      CSF), and B-type natriuretic peptide were also measured. CD34(+) cells, EPCs, TNF
      alpha and receptors, VEGF, SDF-1, and B-type natriuretic peptide were increased
      in HF. CD34(+) cells and EPCs were inversely related to functional class and to
      TNF-alpha, being decreased in New York Heart Association class IV compared with
      class I and II and controls. No role was found for the origin of the disease.
      CONCLUSIONS: CD34(+) cells and EPC mobilization occurs in HF and shows a biphasic
      response, with elevation and depression in the early and advanced phases,
      respectively. This could be related to the myelosuppressive role of TNF-alpha.

PMID- 15249503
TI  - Treatment of left anterior descending coronary artery disease with sirolimus
      eluting stents.
AB  - BACKGROUND: Revascularization strategies often hinge on the presence and degree
      of left anterior descending coronary artery (LAD) stenosis. A decision for bypass
      surgery is often based on the durability of surgical LAD revascularization
      compared with percutaneous approaches. By decreasing restenosis, drug-eluting
      stents may have reduced the "reintervention gap" between surgery and percutaneous
      intervention, making the percutaneous route preferable. METHODS AND RESULTS: Of
      the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized
      to percutaneous intervention with either sirolimus-eluting or bare-metal stents.
      Baseline demographic, clinical, and angiographic data were obtained. Patients had
      1-year clinical and 8-month angiographic follow-up. Baseline characteristics were
      similar in both groups. The majority of lesions were tubular type B lesions
      (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary
      in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the
      bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year
      major adverse events (defined as cardiac death, Q-wave and non-Q-wave myocardial
      infarction, or target vessel revascularization) was decreased 59% in the
      sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to
      0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions
      showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus
      eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major
      adverse events demonstrated a similar trend, with a 50% decrease compared with
      control patients (10.4% versus 20.6%, P=NS). CONCLUSIONS: Sirolimus-eluting
      stents significantly decrease revascularization rates in LAD lesions. At 1 year,
      sirolimus-eluting stent revascularization rates are comparable to historic single
      vessel bypass surgery revascularization rates.

PMID- 15249504
TI  - Evaluation and clinical implications of aortic valve calcification measured by
      electron-beam computed tomography.
AB  - BACKGROUND: Electron-beam computed tomography (EBCT) is used to measure coronary
      calcification but not for aortic valve calcification (AVC). Its accuracy,
      association with aortic stenosis (AS) severity, and diagnostic and prognostic
      value with respect to AVC are unknown. METHODS AND RESULTS: In 30 explanted
      aortic valves, the AVC score by EBCT (1125+/-1294 Agatston units [AU]) showed a
      strong linear correlation (r=0.96, P<0.0001) with valvular calcium weight (653+/
      748 mg) by pathology that allowed estimation of calcium weight as AVC score/1.7,
      with a small standard error of the estimate (53 mg). In 100 consecutive clinical
      patients, we measured AVC by EBCT and AS severity by echocardiographic aortic
      valve area (AVA). The AVC score was 1316+/-1749 AU (range 0 to 7226 AU).
      Intraobserver and interobserver variabilities were excellent (4+/-4% and 4+/-10%,
      respectively). AVC and AVA were strongly associated (r=0.79, P<0.0001) but had a
      curvilinear relationship that suggested that AVC and AVA provide complementary
      information. AVC score > or =1100 AU provided 93% sensitivity and 82% specificity
      for diagnosis of severe AS (AVA <1 cm2), with a receiver operator characteristic
      curve area of 0.89. AVC assessment by echocardiography was often more severe than
      by EBCT (P<0.0001). During follow-up, 22 patients either died, developed heart
      failure, or required surgery. With adjustment for age, sex, symptoms, ejection
      fraction, and AVA, the AVC score was independently predictive of event-free
      survival (risk ratio 1.06 per 100-AU increment [1.02 to 1.10], P<0.001), even
      after adjustment for echocardiographic calcifications. CONCLUSIONS: AVC is
      accurately and reproducibly measured by EBCT and shows a strong association and
      diagnostic value for severe AS. The curvilinear relationship between AVC and AVA
      suggests these measures are complementary, and indeed, AVC provides independent
      outcome information. Thus, AVC is an important measurement in the evaluation of
      patients with AS.

PMID- 15249505
TI  - Coronary artery spatial distribution of acute myocardial infarction occlusions.
AB  - BACKGROUND: Acute coronary occlusions leading to ST-segment elevation myocardial
      infarctions (STEMIs) are due primarily to rupture of atherosclerotic plaques.
      Present "vulnerable plaque" detection technology focuses on identifying
      individual plaques with no clear therapeutic plan beyond conventional risk factor
      reduction. We developed a spatial map of the distribution of acute coronary
      occlusions to test our hypothesis that plaque ruptures do not occur uniformly
      throughout the coronary tree. METHODS AND RESULTS: We analyzed 208 consecutive
      patients who presented to the Brigham and Women's Hospital with STEMI and mapped
      the location of the acute coronary occlusion. These occlusions were not uniformly
      distributed throughout each of the major epicardial coronary arteries but tended
      to cluster within the proximal third of each of the vessels (right coronary
      artery, P=0.001; left anterior descending artery, P=0.003; left circumflex
      artery, P=0.001). Furthermore, Poisson regression showed that for each 10-mm
      increase in distance from the ostium, the risk of an acute coronary occlusion was
      significantly decreased by 13% in the right coronary artery, 30% in the left
      anterior descending artery, and 26% in the left circumflex artery. CONCLUSIONS:
      Acute coronary occlusions leading to STEMI tend to cluster in predictable "hot
      spots" within the proximal third of the coronary arteries. Identification of
      these high-risk zones for acute coronary occlusions will lead to future advances
      in vulnerable plaque detection technology and potentially locally directed
      preventive strategies.

PMID- 15249506
TI  - gp91phox-dependent expression of platelet CD40 ligand.
AB  - BACKGROUND: CD40 ligand (CD40L) expression on platelets is mediated by agonists,
      but the underlying mechanism is still unclear. METHODS AND RESULTS: CD40L
      expression was measured in platelets from healthy subjects both with and without
      the addition of antioxidants or a phospholipase A2 (PLA2) inhibitor and in
      platelets from 2 patients with an inherited deficiency of gp91phox.
      Immunoprecipitation analysis was also performed to determine whether normal
      platelets showed gp91phox expression. Unlike catalase and mannitol, superoxide
      dismutase inhibited agonist-induced platelet CD40L expression in healthy
      subjects. Immunoprecipitation analysis also showed that platelets from healthy
      subjects expressed gp91phox. In 2 male patients with inherited gp91phox
      deficiency, collagen-, thrombin-, and arachidonic acid-stimulated platelets
      showed an almost complete absence of superoxide anion (O(2)(-)) and CD40L
      expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor
      almost completely prevented agonist-induced O(2)(-) and CD40L expression.
      CONCLUSIONS: These data provide the first evidence that platelet CD40L expression
      occurs via arachidonic acid-mediated gp91phox activation.

PMID- 15249507
TI  - Heterogeneous beta2-adrenoceptor expression and dilation in coronary arterioles
      across the left ventricular wall.
AB  - BACKGROUND: Previous in vivo studies have shown that beta-adrenoceptor agonists
      cause a redistribution of coronary flow away from the subendocardium; however,
      the underlying mechanism remains uncertain. We tested the hypothesis that a
      heterogeneous distribution of beta-adrenoceptors and their vasomotor responses
      exists in the coronary microcirculation across the left ventricular wall. METHODS
      AND RESULTS: Porcine subepicardial and subendocardial arterioles (<100 microm)
      were isolated from the left ventricle and pressurized for in vitro study of
      vasodilation to the nonselective beta-adrenoceptor agonist isoproterenol and the
      selective beta2-adrenoceptor agonist procaterol. Both vessel types developed a
      similar level of basal tone and dilated to isoproterenol and procaterol. However,
      subepicardial arterioles exhibited a much higher sensitivity and greater dilation
      capacity to both agonists. The isoproterenol-induced vasodilations were inhibited
      by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker. In
      contrast to isoproterenol, dilations of subepicardial and subendocardial
      arterioles to pinacidil, a K(ATP) channel opener, were similar. In both vessel
      types, isoproterenol-induced dilation was inhibited by the beta2-adrenoceptor
      blocker ICI-118,551 but was insensitive to the beta1-adrenoceptor blocker
      atenolol. Reverse transcription-polymerase chain reaction and immunohistochemical
      data revealed that beta2-adrenoceptor mRNA and protein expression, respectively,
      were markedly greater in subepicardial arterioles. CONCLUSIONS: This study
      demonstrates that selective activation of beta2-adrenoceptors elicits dilation of
      both subepicardial and subendocardial arterioles through opening of K(ATP)
      channels. The higher beta2-adrenoceptor expression in subepicardial arterioles
      may contribute to the greater dilation of these vessels to beta2-adrenoceptor
      activation.

PMID- 15249508
TI  - Aldosterone directly induces myocyte apoptosis through calcineurin-dependent
      pathways.
AB  - BACKGROUND: Aldosterone has recently attracted considerable attention for its
      involvement in the pathophysiology of heart failure, in which apoptotic cell loss
      plays a critical role. This study examined whether aldosterone directly induces
      myocyte apoptosis via its specific receptors. METHODS AND RESULTS: Neonatal rat
      cardiac myocytes were exposed to aldosterone (10(-8) to 10(-5) mol/L). Nuclear
      staining with Hoechst 33258 showed that aldosterone induced myocyte apoptosis in
      a dose- and time-dependent fashion. Treatment of myocytes with 10(-5) mol/L
      aldosterone significantly increased the percentage of apoptosis (15.5+/-1.4%)
      compared with serum-deprived control (7.3+/-0.6%). Radio ligand binding assay
      revealed the existence of plasma membrane receptor with high affinity (K(d), 0.2
      nmol/L) for aldosterone in cardiac myocytes but not in fibroblasts. Aldosterone
      rapidly (approximately 30 seconds) mobilized [Ca2+]i that was blocked by
      neomycin. Aldosterone induced dephosphorylation of the proapoptotic protein Bad,
      enhancement of mitochondrial permeability transition, decrease in mitochondrial
      membrane potential, and release of cytochrome c from the mitochondria into the
      cytosol with concomitant activation of caspase-3. These effects of aldosterone
      were inhibited by concurrent treatment with either an L-type Ca2+ channel
      antagonist, nifedipine, or inhibitors for the Ca2+-dependent phosphatase
      calcineurin, cyclosporin A and FK506. CONCLUSIONS: The present study demonstrates
      for the first time that the specific plasma membrane receptor (coupled with
      phospholipase C) for aldosterone is present on cardiac myocytes and that
      aldosterone accelerates the mitochondrial apoptotic pathway through activation of
      calcineurin and dephosphorylation of Bad, suggesting that the proapoptotic action
      of aldosterone may directly contribute to the progression of heart failure.

PMID- 15249509
TI  - Association of atrial fibrillation and obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with recurrent atrial
      fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients
      who are male, obese, and/or hypertensive, but its prevalence in patients with AF
      is unknown. METHODS AND RESULTS: We prospectively studied consecutive patients
      undergoing electrocardioversion for AF (n=151) and consecutive patients without
      past or current AF referred to a general cardiology practice (n=312). OSA was
      diagnosed with the Berlin questionnaire, which is validated to identify patients
      with OSA. We also assessed its accuracy compared with polysomnography in a sample
      of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and
      chi2 tests. Logistic regression modeled the association of AF and OSA after
      adjustment for relevant covariates. Patients in each group had similar age,
      gender, body mass index, and rates of diabetes, hypertension, and congestive
      heart failure. The questionnaire performed with 0.86 sensitivity, 0.89
      specificity, and 0.97 positive predictive value in our sample. The proportion of
      patients with OSA was significantly higher in the AF group than in the general
      cardiology group (49% versus 32%, P=0.0004). The adjusted odds ratio for the
      association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, P=0.0006).
      CONCLUSIONS: The novel finding of this study is that a strong association exists
      between OSA and AF, such that OSA is strikingly more prevalent in patients with
      AF than in high-risk patients with multiple other cardiovascular diseases. The
      coinciding epidemics of obesity and AF underscore the clinical importance of
      these results.

PMID- 15249510
TI  - Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular
      function in heart failure.
AB  - BACKGROUND: We tested the hypothesis that intracoronary delivery of an adenovirus
      encoding adenylyl cyclase type VI (Ad.AC(VI)) would be associated with increased
      left ventricular (LV) function in pigs with congestive heart failure. METHODS AND
      RESULTS: Pigs (52+/-6 kg; n=16) underwent placement of pacemakers, LV pressure
      transducers, and left atrial and aortic catheters. Physiological and
      echocardiographic studies were obtained from conscious animals 13 days later, and
      pacing was initiated (220 bpm). Seven days later, measures of LV function were
      reduced, documenting severe LV dysfunction and dilation. Pigs then received
      intracoronary Ad.AC(VI) (1.4x10(12) vp; n=7) or saline (PBS; n=9) (randomized,
      blinded), with concomitant infusion of nitroprusside (50 microg/min, 6.4 minutes)
      to increase gene transfer. Pacing was continued for 14 days, and final studies
      were obtained. The a priori key end point was change in LV dP/dt during
      isoproterenol infusion (pre-Ad.AC(VI) value minus value after 21 days of pacing).
      Pigs receiving Ad.AC(VI) showed a smaller decrease in both LV +dP/dt (P=0.0014)
      and LV -dP/dt (P=0.0008). Serial echocardiography showed that Ad.AC(VI) treatment
      was associated with increased LV function and reduced LV dilation and that end
      systolic wall stress was reduced. AC-stimulated cAMP production was increased 1.7
      fold in LV samples from Ad.AC(VI)-treated pigs (P=0.006), and B-type natriuretic
      peptide was reduced (0.035). Gene transfer was confirmed by polymerase chain
      reaction. CONCLUSIONS: AC(VI) gene transfer increases LV function and attenuates
      deleterious LV remodeling in congestive heart failure.

PMID- 15249511
TI  - High levels of dietary advanced glycation end products transform low-density
      lipoprotein into a potent redox-sensitive mitogen-activated protein kinase
      stimulant in diabetic patients.
AB  - BACKGROUND: LDL modification by endogenous advanced glycation end products (AGEs)
      is thought to contribute to cardiovascular disease of diabetes. It remains
      unclear, however, whether exogenous (diet-derived) AGEs influence glycoxidation
      and endothelial cell toxicity of diabetic LDL. METHODS AND RESULTS: Twenty-four
      diabetic subjects were randomized to either a standard diet (here called high
      AGE, HAGE) or a diet 5-fold lower in AGE (LAGE diet) for 6 weeks. LDL pooled from
      patients on HAGE diet (Db-HAGE-LDL) was more glycated than LDL from the LAGE diet
      group (Db-LAGE-LDL) (192 versus 92 AGE U/mg apolipoprotein B) and more oxidized
      (5.7 versus 1.5 nmol malondialdehyde/mg lipoprotein). When added to human
      endothelial cells (ECV 304 or human umbilical vein endothelial cells), Db-HAGE
      LDL promoted marked ERK1/2 phosphorylation (pERK1/2) (5.5- to 10-fold of control)
      in a time- and dose-dependent manner compared with Db-LAGE-LDL or native LDL. In
      addition, Db-HAGE-LDL stimulated NF-kappaB activity significantly in ECV 304 and
      human umbilical vein endothelial cells (2.3-fold above baseline) in a manner
      inhibitable by a MEK inhibitor PD98059 (10 micromol/L), the antioxidant N-acetyl
      l-cysteine, NAC (30 mmol/L), and the NADPH oxidase inhibitor DPI (20 micromol/L).
      In contrast to Db-LAGE-LD and native LDL, Db-HAGE-LDL induced significant soluble
      vascular cell adhesion molecule-1 production (2.3-fold), which was blocked by
      PD98059, NAC, and DPI. CONCLUSIONS: Exposure to daily dietary glycoxidants
      enhances LDL-induced vascular toxicity via redox-sensitive mitogen-activated
      protein kinase activation. This can be prevented by dietary AGE restriction.

PMID- 15249512
TI  - Glycated hemoglobin level is strongly related to the prevalence of carotid artery
      plaques with high echogenicity in nondiabetic individuals: the Tromso study.
AB  - BACKGROUND: High levels of HbA1c have been associated with increased mortality
      and an increased risk of atherosclerosis assessed as carotid intima-media
      thickness or plaque prevalence. In the present population-based study, we
      examined the association between HbA1c and plaque prevalence with emphasis on
      plaque echogenicity in subjects not diagnosed with diabetes. METHODS AND RESULTS:
      HbA1c measurements and ultrasonography of the carotid artery were performed in
      5960 subjects (3026 women, 2934 men) 25 to 84 years of age. Plaque morphology was
      categorized into 4 groups from low echogenicity (soft plaque) to strong
      echogenicity (hard plaque). HbA1c was categorized into 5 groups: <5.0%, 5.0% to
      5.4%, 5.5% to 5.9%, 6.0% to 6.4% and >6.4%. Carotid plaque prevalence increased
      with increasing HbA1c level (P for linear trend=0.002). The OR for hard plaques
      versus no plaques was 5.8 in the highest HbA1c group (>6.4%) compared with
      subjects in the lowest group (<5.0%) after adjustment for several possible
      confounders. The risk of predominantly hard plaques was also significantly
      associated with HbA1c levels, although the ORs at each level were somewhat lower
      than for hard plaques. With respect to the risk of soft plaques versus no
      plaques, no statistically significant relationship with HbA1c levels was found.
      CONCLUSIONS: Metabolic changes reflected by HbA1c levels may contribute to the
      development of hard carotid artery plaques, even at modestly elevated levels.

PMID- 15249513
TI  - Acute coronary syndrome biomarkers: the need for more adequate reporting.

PMID- 15249514
TI  - Randomized clinical trials: how long should they last?

PMID- 15249515
TI  - Titin isoforms in heart failure: are there benefits to supersizing?

PMID- 15249516
TI  - Implications of recent clinical trials for the National Cholesterol Education
      Program Adult Treatment Panel III guidelines.
AB  - The Adult Treatment Panel III (ATP III) of the National Cholesterol Education
      Program issued an evidence-based set of guidelines on cholesterol management in
      2001. Since the publication of ATP III, 5 major clinical trials of statin therapy
      with clinical end points have been published. These trials addressed issues that
      were not examined in previous clinical trials of cholesterol-lowering therapy.
      The present document reviews the results of these recent trials and assesses
      their implications for cholesterol management. Therapeutic lifestyle changes
      (TLC) remain an essential modality in clinical management. The trials confirm the
      benefit of cholesterol-lowering therapy in high-risk patients and support the ATP
      III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL.
      They support the inclusion of patients with diabetes in the high-risk category
      and confirm the benefits of LDL-lowering therapy in these patients. They further
      confirm that older persons benefit from therapeutic lowering of LDL-C. The major
      recommendations for modifications to footnote the ATP III treatment algorithm are
      the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL,
      but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option,
      ie, a reasonable clinical strategy, on the basis of available clinical trial
      evidence. This therapeutic option extends also to patients at very high risk who
      have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high
      triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration
      can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug.
      For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%),
      the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a
      therapeutic option on the basis of recent trial evidence. The latter option
      extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129
      mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high
      risk persons, it is advised that intensity of therapy be sufficient to achieve at
      least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk
      or moderately high risk who has lifestyle-related risk factors (eg, obesity,
      physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is
      a candidate for TLC to modify these risk factors regardless of LDL-C level.
      Finally, for people in lower-risk categories, recent clinical trials do not
      modify the goals and cutpoints of therapy.

PMID- 15249517
TI  - Perspective on selected issues in cardiovascular disease research with a focus on
      black Americans.

PMID- 15249518
TI  - Images in cardiovascular medicine. Complicated case of left ventricular
      echinococcosis.

PMID- 15249519
TI  - The commercialization of clinical research: who pays the piper, calls the tune?

PMID- 15249520
TI  - Achieving involvement: process outcomes from a cluster randomized trial of shared
      decision making skill development and use of risk communication aids in general
      practice.
AB  - BACKGROUND: A consulting method known as 'shared decision making' (SDM) has been
      described and operationalized in terms of several 'competences'. One of these
      competences concerns the discussion of the risks and benefits of treatment or
      care options-'risk communication'. Few data exist on clinicians' ability to
      acquire skills and implement the competences of SDM or risk communication in
      consultations with patients. OBJECTIVE: The aims of this study were to evaluate
      the effects of skill development workshops for SDM and the use of risk
      communication aids on the process of consultations. METHODS: A cluster randomized
      trial with crossover was carried out with the participation of 20 recently
      qualified GPs in urban and rural general practices in Gwent, South Wales. A total
      of 747 patients with known atrial fibrillation, prostatism, menorrhagia or
      menopausal symptoms were invited to a consultation to review their condition or
      treatments. Half the consultations were randomly selected for audio-taping, of
      which 352 patients attended and were audio-taped successfully. After baseline,
      participating doctors were randomized to receive training in (i) SDM skills or
      (ii) the use of simple risk communication aids, using simulated patients. The
      alternative training was then provided for the final study phase. Patients were
      allocated randomly to a consultation during baseline or intervention 1 (SDM or
      risk communication aids) or intervention 2 phases. A randomly selected half of
      the consultations were audio-taped from each phase. Raters (independent, trained
      and blinded to study phase) assessed the audio-tapes using a validated scale to
      assess levels of patient involvement (OPTION: observing patient involvement), and
      to analyse the nature of risk information discussed. Clinicians completed
      questionnaires after each consultation, assessing perceived clinician-patient
      agreement and level of patient involvement in decisions. Multilevel modelling was
      carried out with the OPTION score as the dependent variable, and rater,
      consultation and clinician levels of data, standardized by rater within
      clinician. RESULTS: Following each of the interventions, the clinicians
      significantly increased their involvement of patients in decision making (OPTION
      score increased by 10.6 following risk communication training [95% confidence
      interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95%
      CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement
      achieved by the risk communication aids was significantly increased by the
      subsequent introduction of the skill development workshops (7.7 increase in
      OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills
      followed by risk communication aids) did not achieve this effect. The use of most
      risk information formats increased after the provision of specific risk
      communication aids (P < 0.001). Clinicians using the risk communication tools
      perceived significantly higher patient and clinician agreement on treatment (P <
      0.001), patient satisfaction with information (P < 0.01), clinician satisfaction
      with decision (P < 0.01) and general overall satisfaction with the consultation
      (P < 0.001) than those who were exposed to SDM skill development workshops.
      CONCLUSIONS: These clinicians were able to acquire the skills to implement SDM
      competences and to use risk communication aids. Each intervention provided
      independent effects. Further progress towards greater patient involvement in
      health care decision making is possible, and skill development in this area
      should be incorporated into postgraduate professional development programmes.

PMID- 15249521
TI  - Patient-based outcome results from a cluster randomized trial of shared decision
      making skill development and use of risk communication aids in general practice.
AB  - BACKGROUND: Shared decision-making (SDM) between professionals and patients is
      increasingly advocated from ethical principles. Some data are accruing about the
      effects of such approaches on health or other patient-based outcomes. These
      effects often vary substantially between studies. OBJECTIVE: Our aim was to
      evaluate the effects of training GPs in SDM, and the use of simple risk
      communication aids in general practice, on patient-based outcomes. METHODS: A
      cluster randomized trial with crossover was carried out with the participation of
      20 recently qualified GPs in urban and rural general practices in Gwent, South
      Wales. A total of 747 patients with known atrial fibrillation, prostatism,
      menorrhagia or menopausal symptoms were invited to a consultation to review their
      condition or treatments. After baseline, participating doctors were randomized to
      receive training in (i) SDM skills; or (ii) the use of simple risk communication
      aids, using simulated patients. The alternative training was then provided for
      the final study phase. Patients were randomly allocated to a consultation during
      baseline or intervention 1 (SDM or risk communication aids) or intervention 2
      phases. A randomly selected half of the consultations took place in 'research
      clinics' to evaluate the effects of more time for consultations, compared with
      usual surgery time. Patient-based outcomes were assessed at exit from
      consultation and 1 month follow-up. These were: COMRADE instrument (principal
      measures; subscales of risk communication and confidence in decision), and a
      range of secondary measures (anxiety, patient enablement, intention to adhere to
      chosen treatment, satisfaction with decision, support in decision making and SF
      12 health status measure). Multilevel modelling was carried out with outcome
      score as the dependent variable, and follow-up point (i.e. exit or 1 month later
      for each patient), patient and doctor levels of explanatory variables. RESULTS:
      No statistically significant changes in patient-based outcomes due to the
      training interventions were found: COMRADE risk communication score increased 0.7
      [95% confidence interval (CI) -0.92 to 2.32] after risk communication training
      and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with
      communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk
      communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training.
      Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and
      expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P <
      0.05) were significantly greater among patients seen in the research clinics
      (when more time was available) compared with usual surgery time. Most outcomes
      deteriorated between exit and 1 month later. There was no interaction between
      intervention effects. CONCLUSION: Patients can be more involved in treatment
      decisions, and risks and benefits of treatment options can be explained in more
      detail, without adversely affecting patient-based outcomes. SDM and risk
      communication may be advocated from values and ethical principles even without
      evidence of health gain or improvement in patient-based outcomes, but the
      resources required to enhance these professional skills must also be taken into
      consideration. These data also indicate the benefits of extra consultation time.

PMID- 15249522
TI  - Adjusting for case mix and social class in examining variation in home visits
      between practices.
AB  - OBJECTIVES: The purpose of this study was to investigate whether adjusting for
      clinical case mix and social class explains more of the variation in home visits
      between general practices than adjusting for age and sex alone. METHODS: The
      setting was 60 general practices in England and Wales taking part in the 1 year
      Fourth National Morbidity Survey. The participants comprised 349 505 patients who
      were registered with one of the participating general practices for at least 180
      days, and who had at least one consultation during the period. The outcome
      measure is whether or not a patient received a home visit in that year. A
      clinical case mix category (morbidity class) based on 1 year's diagnostic
      information was assigned to each patient using the Johns Hopkins Adjusted
      Clinical Groups (ACG) Case Mix System. The social class measure was derived from
      occupation and employment status and is similar to that of the 1991 UK census.
      Variations in home visits between practices were examined using multilevel
      logistic regression models. The variability between practices before and after
      adjusting for clinical case mix and social class was estimated using the
      intracluster correlation coefficient (ICC). RESULTS: The overall percentage of
      patients receiving a home visit over the 1 year study period was 17%, and this
      varied from 7 to 31% across the 60 practices. The percentage of the total
      variation in home visits attributable to differences between practices was 2.5%
      [95% confidence interval (CI) 1.4-3.2%] after adjusting for age and sex. This
      reduced to 1.6% (95% CI 1.1-2.4%) after taking into account morbidity class. The
      results were similar when social class was included instead of morbidity class.
      Morbidity and social class together reduced variation in home visits between
      practices to 1.5% (95% CI 1.1-2.2%). CONCLUSIONS: Age, sex, social class and
      clinical case mix are strong determinants of home visits in the UK. Adjusting for
      morbidity and social class results in a small improvement in explaining the
      variability in home visits between practices compared with adjusting for age and
      sex alone. There is far more variation between patients within practices;
      however, it is not straightforward to examine the factors influencing this
      variation. In addition to morbidity and social class, there could also be other
      unmeasured factors such as varying patient demand for home visits, disability or
      differences in GP home visiting practice style that could influence the large
      within-practice variability observed in this study.

PMID- 15249523
TI  - Differences in treatment regimes, consultation frequency and referral patterns of
      diabetes mellitus in general practice in five European countries.
AB  - BACKGROUND: In many European countries, maturity onset diabetes mellitus (DM) is
      to a large extent managed in general practice. OBJECTIVE: Our aim was to compare
      management of DM in general practice in five European countries in order to
      contribute to international guidelines on the management of DM by GPs. METHODS:
      Routine monitoring of patients presenting with DM was performed during a 12 month
      period (1999-2000) to GPs in established sentinel practice surveillance networks
      in five European countries (Belgium, Croatia, England, Spain and The
      Netherlands). Results were stratified by age and country. RESULTS: The proportion
      of patients treated by diet only varied from 13% (The Netherlands) to 25%
      (Spain); diet and oral antidiabetics from 51% (England) to 62% (Belgium); a
      combination of diet and insulin varied from 15% (Belgium and Croatia) to 26% (The
      Netherlands); and a combination of diet, oral antidiabetics and insulin was <10%
      in all countries. In the older age groups, insulin is prescribed most frequently
      in The Netherlands. Spain and Croatia show high consultation rates for DM;
      England and The Netherlands show low rates. Referral percentages vary
      considerably between countries (highest in Croatia). CONCLUSIONS: National
      differences found included the use of insulin in the elderly, the consultation
      frequency in general practice and the referral rate to ophthalmologist and
      diabetic specialists. Further quantitative and qualitative studies are needed to
      explore the needs for support in diabetes management in general practice in
      Europe.

PMID- 15249524
TI  - Stimulant use: an investigation into population characteristics and service
      provision.

PMID- 15249525
TI  - An evaluation of prompt access to physiotherapy in the management of low back
      pain in primary care.
AB  - BACKGROUND: Disability arising from low back pain (LBP) is a growing problem.
      Current primary care management of LBP has been criticized for its mechanistic
      basis and for delays in gaining access to specialist advice. Among recent
      recommendations made for improved management are functional explanatory models, a
      rehabilitative approach and early access to physical therapy. It is not known if
      these recommendations can be implemented in mainstream primary care. OBJECTIVE:
      The purpose of our study was to examine the feasibility, acceptability and
      component costs of providing a prompt access physiotherapy service for new
      episodes of LBP in primary care; to describe outcomes and compare them with other
      published interventions; and to explore the influence of the service on GPs'
      approach to LBP. METHODS: Back pain clinics staffed by a physiotherapist were
      established in a group of demographically representative practices in a typical
      UK health authority. Adult patients with a new episode of LBP referred by their
      GPs were managed in accordance with recent recommendations. Data on pain,
      disability and well-being were collected at recruitment and some 12 weeks later.
      Patient diaries and interviews with GPs before and after the study provided
      qualitative data. Comparative costings were derived from national and local
      sources. RESULTS: A total of 614 patients, representing 3.2% of the adult
      population, were referred, of whom 522 (85%) were seen at the back pain clinics
      within 3-4 days, the majority within 72 h. Although this represents less than
      half the adult patients thought to be presenting to their GPs with LBP, patients
      exhibited levels of pain and disability comparable with those described in other
      studies of LBP in primary care. More than 70% of patients required only a single
      clinic visit and <5% were referred on to specialist orthopaedic or back pain
      rehabilitation services. At follow-up, levels of improvement were comparable with
      and time taken off work superior to those seen in other intervention studies of
      LBP in primary care. Prompt access to physiotherapy in primary care costs less
      per episode of LBP than conventional management. Qualitative data suggest that
      patients valued early access to the physiotherapist, particularly for the
      reassurance provided. Interviews with GPs revealed strong support for the
      service, in large part based on favourable feedback from patients. CONCLUSIONS:
      For primary care patients with a new episode of LBP referred by their GP, prompt
      access to a dedicated physiotherapy service is both feasible and acceptable.
      Comparison with other published interventions suggests that it is also cost
      effective and that a typical Primary Care Trust (PCT) would rapidly recoup the
      cost of additional physiotherapists. However, questions remain about the
      availability of sufficient physiotherapists to make such a service available
      nationally. The influence of the service upon GPs' own approach to the management
      of LBP is likely to be gradual and to come about largely through positive
      feedback from patients.

PMID- 15249526
TI  - Defining chronic conditions for primary care with ICPC-2.
AB  - BACKGROUND: With the increasing prevalence of chronic conditions, there is need
      for a standardized definition of chronicity for use in research, to evaluate the
      population prevalence and general practice management of chronic conditions.
      OBJECTIVES: Our aims were to determine the characteristics required to define
      chronicity, apply them to a primary care classification and provide a defined
      codeset of chronic conditions. METHODS: A literature review evaluated
      characteristics used to define chronic conditions. The final set of
      characteristics was applied to the International Classification of Primary Care
      Version 2 (ICPC-2) through more specific terms available in ICPC-2 PLUS, an
      extended terminology classified to ICPC-2. A set of ICPC-2 rubrics was delineated
      as representing chronic conditions. RESULTS: Factors found to be relevant to a
      definition of chronic conditions for research were: duration; prognosis; pattern;
      and sequelae. Within ICPC-2, 129 rubrics were described as 'chronic', and another
      20 rubrics had elements of chronicity. Duration was the criterion most frequently
      satisfied (98.4% of chronic rubrics), while 88.2% of rubrics met at least three
      of the four criteria. CONCLUSION: Monitoring the prevalence and management of
      chronic conditions is of increasing importance. This study provided evidence for
      multifaceted definitions of chronicity. While all characteristics examined could
      be used by those interested in chronicity, the list has been designed to identify
      chronic conditions managed in Australian general practice, and is therefore not a
      nomenclature of all chronic conditions. Subsequent analysis of chronic conditions
      using pre-existing data sets will provide a baseline measure of chronic condition
      prevalence and management in general practice.

PMID- 15249527
TI  - Variation in test ordering behaviour of GPs: professional or context-related
      factors?
AB  - OBJECTIVE: The aim of this study was to describe GPs' test ordering behaviour,
      and to establish professional and context-related determinants of GPs'
      inclination to order tests. METHODS: A cross-sectional analysis was carried out
      of 229 GPs in 40 local GP groups from five regions in The Netherlands of the
      combined number of 19 laboratory and eight imaging tests ordered by GPs,
      collected from five regional diagnostic centres. In a multivariable multilevel
      regression analysis, these data were linked with survey data on professional
      characteristics such as knowledge about and attitude towards test ordering, and
      with data on context-related factors such as practice type or experience with
      feedback on test ordering data. The main outcome measure was the percentage point
      differences associated with professional and context-related factors. RESULTS:
      The total median number of tests per GP per year was 998 (interquartile range 663
      1500), with significant differences between the regions. The response to the
      survey was 97%. At the professional level, 'individual involvement in developing
      guidelines' (yes versus no), and at the context-related level 'group practice'
      (versus single-handed and two-person practices) and 'more than 1 year of
      experience working with a problem-oriented laboratory order form' (yes versus no)
      were associated with 27, 18 and 41% lower numbers of tests ordered, respectively.
      CONCLUSION: In addition to professional determinants, context-related factors
      appeared to be strongly associated with the numbers of tests ordered. Further
      studies on GPs' test ordering behaviour should include local and regional
      factors.

PMID- 15249528
TI  - Quality of morbidity coding in general practice computerized medical records: a
      systematic review.
AB  - BACKGROUND: Increased use of computers and morbidity coding in primary care
      delivery and research brings a need for evidence of the quality of general
      practice medical records. OBJECTIVE: Our aim was to assess the quality, in terms
      of completeness and correctness, of morbidity coding in computerized general
      practice records through a systematic review. METHODS: Published studies were
      identified by searches of electronic databases and citations of collected papers.
      Assessment of each article was made by two independent observers and
      discrepancies resolved by consensus. Studies were reviewed qualitatively due to
      their heterogeneity. RESULTS: Twenty-four studies met the inclusion criteria for
      the review. There was variation in the methodology and quality of studies, and
      problems in generalizability. Studies have attempted to assess the completeness
      and correctness of morbidity registers by reference to a gold standard such as
      paper notes, prescribing information or diagnostic tests and procedures, each of
      which has problems. A consistent finding was that quality of recording varied
      between morbidities. One reason for this may be in distinctiveness of diagnosis
      (e.g. coding of diabetes tended to be of higher quality than coding of asthma).
      CONCLUSIONS: This review highlights the problems faced in assessing the
      completeness and correctness of computerized general practice medical records.
      However, it also suggests that a high quality of coding can be achieved. The
      focus should now be on methods to encourage and help practices improve the
      quality of their coding.

PMID- 15249529
TI  - Management of earwax in primary care--postal survey of UK GPs and practice
      nurses.

PMID- 15249531
TI  - Risk factors for hypertensive crisis: importance of out-patient blood pressure
      control.
AB  - OBJECTIVES: The purpose of this study was to identify independent risk factors
      for development of hypertensive crisis. METHODS: This was a retrospective, case
      controlled study. Cases were 143 patients who presented during a 3-year period to
      the Emergency Department with the diagnosis of hypertensive crisis, defined as
      systolic pressure >/=180 mmHg and/or diastolic pressure >/=110 mmHg and symptoms
      of hypertensive emergency during the Emergency Department presentation. Controls
      were 485 patients with hypertension, matched to cases on the basis of age, sex
      and race, who were not admitted to the Emergency Department with an episode of
      hypertensive crisis during the study period. Co-morbid conditions were identified
      from computerized health system databases and medical records. Out-patient blood
      pressures were obtained from medical records from randomly selected out-patient
      clinic visits. RESULTS: The average blood pressure during Emergency Department
      presentation in patients with hypertensive crisis was 197 +/- 21/108 +/- 14 mmHg.
      Less successful out-patient systolic blood pressure control was an independent
      risk factor for hypertensive crisis [odds ratio (OR) 1.30 (1.18-1.42), per 10
      mmHg, P < 0.001]. Higher out-patient diastolic blood pressures [OR 1.21 (0.99
      1.43 per 10 mmHg, P = 0.07] and history of heart failure [OR 3.48 (0.94-12.94), P
      = 0.06] trended towards independence as risk factors. CONCLUSION: Less effective
      blood pressure control, based on out-patient systolic blood pressure
      measurements, is an independent risk factor for an Emergency Department
      presentation due to hypertensive crisis.

PMID- 15249530
TI  - The clinical and economic burden of fibromyalgia compared with diabetes mellitus
      and hypertension among Bedouin women in the Negev.
AB  - BACKGROUND: Fibromyalgia (FM) is a common idiopathic chronic, widespread pain
      syndrome with tenderness in anatomically defined tender points. OBJECTIVES: The
      purpose of the present study was to describe and characterize the economic and
      daily work burden of FM compared with diabetes mellitus and hypertension.
      METHODS: A retrospective study was conducted in 2001 in a primary care clinic,
      the Kuseife clinic of the Clalit Health Services. Data for the three study groups
      were obtained from the computerized database of the Kuseife clinic and the Negev
      District, Israel. The study group included 102 FM patients. The control groups
      included 102 diabetes patients and 103 patients with hypertension. RESULTS:
      Hospitalization and hospital day care services were the main expenses incurred by
      patients in this study. There were no differences among the study groups in any
      cost parameter examined except for the cost of diagnostic tests (P < 0.01), which
      was less for FM patients. FM patients were referred to specialists and diagnostic
      procedures more frequently than the control groups. No statistical difference was
      found in the total number of clinic visits, but FM patients visited physicians
      more frequently and visited nurses less frequently than patients in the other two
      groups (P < 0.05). CONCLUSIONS: FM patients consume health care resources to a
      similar extent to patients with other chronic diseases such as diabetes mellitus
      and hypertension, but the latter usually receive much more attention from the
      health care system. Greater awareness of this disorder can improve management and
      facilitate planning of health care resources, thus improving quality of care.

PMID- 15249532
TI  - GPs' needs for practice-oriented nutrition education; a Delphi study among Dutch
      GPs.
AB  - BACKGROUND: Published guidelines and lists of topics in nutrition education for
      GPs are affected by practical drawbacks, which prevent them from being easily
      implemented in vocational training curricula. OBJECTIVE: Our aim was to draw up a
      concise priority list of disease-related nutrition topics reflecting the needs
      among Dutch GPs for nutrition education geared to everyday practice, which can be
      used to decide on the main topics and educational content of computer-based
      instruction. METHODS: This was a two-round Delphi study, using pilot-tested
      questionnaires carried out among 41 GPs who attended a national CME meeting on
      nutrition in The Netherlands. Sum scores of, and summarized comments on nutrition
      topics and their frequencies in top-10 lists drawn up by respondents were the
      main outcome measures. RESULTS: The response in both Delphi rounds was high (93
      and 95%). Analysis of questionnaires in both rounds yielded a priority list of
      disease-related nutrition topics, with the 14 highest ranking topics identical in
      both rounds. A fifteenth topic, only found in the second questionnaire, completed
      the priority list. A group of experts assessed this list as fully acceptable.
      CONCLUSION: It was possible to compile a priority list of disease-related
      nutrition topics reflecting the needs of GPs for nutrition education. Based on
      the results of the Delphi study, we generated the following list of five priority
      topics: weight problems; diabetes mellitus; hypercholesterolaemia; intestinal
      complaints; and hypertension. This list of five and the summarized comments of
      respondents will determine the main topics and educational content of a computer
      based instruction we are currently developing.

PMID- 15249533
TI  - Feasibility and acceptability of a physical activity promotion programme in
      general practice.
AB  - BACKGROUND: Physical activity promotion in general practice is advocated though
      not incorporated into daily practice. Several barriers must be overcome to
      develop a feasible and acceptable programme. OBJECTIVE: The aim of this study was
      to conduct a process evaluation of a physical activity promotion programme in
      general practice (PACE), in which patients visited their provider (GP or practice
      nurse) twice. METHODS: Process evaluation was conducted by means of telephone
      administered, semi-structured interviews with providers and practice assistants.
      The main topics of the interviews were overall impression of PACE, PACE training,
      content and usability of the intervention materials, counselling, implementation
      of the intervention, and opportunities for future use. RESULTS: In the 15
      participating general practices, a total of 17 providers and 12 practice
      assistants were interviewed. The overall impression of the PACE programme was
      positive. Most providers experienced the provided material and training as
      helpful. Some problems concerning the number of forms used and patients having
      difficulties completing the forms were mentioned. Most providers (70.6%) spend 10
      min or more discussing PACE during the first consultation. The second
      consultation mostly was completed within 10 min. Patients overestimating their
      level of physical activity was mentioned as the main barrier in providing the
      counselling. PACE was evaluated as suitable for implementation in Dutch general
      practice, and 60% of the providers actually intended using PACE in the future.
      CONCLUSION: The PACE programme was evaluated as being both acceptable and
      feasible in a selection of Dutch general practices. Positive adaptations will be
      made in order to implement PACE successfully in general practice at a wider
      scale.

PMID- 15249534
TI  - Psychosocial care for cancer patients in primary care? Recognition of
      opportunities for cancer care.
AB  - The paper outlines psychosocial problems experienced by cancer patients and the
      current barriers to service delivery. New models of psychosocial service
      provision are put forward, emphasizing information, communication and technology
      aids in an attempt to improve co-ordination of care. The management of cancer
      patients has evolved greatly over the past decades, and patients are well placed
      to benefit from the experiences of primary care professionals in the delivery of
      chronic illness disease management strategies.

PMID- 15249535
TI  - A pilot study to validate modification of the Duke University Severity of Illness
      scale to measure a family's burden of illness.
AB  - BACKGROUND: Measurement of burden of illness is rarely undertaken in general
      practice, although a specific tool [Duke University Severity of Illness DUSOI
      scale] has been incorporated in the International Classification in Primary Care.
      This measures the burden of illness in an individual at a point in time. There
      has not been any measure of the burden of illness in families. Such an instrument
      would allow measurement of the impact of events on the health of families.
      OBJECTIVE: This pilot study aimed to modify the DUSOI to measure a family's
      burden of illness and to validate any changes. METHODS: The DUSOI was modified to
      measure the mean burden of illness in a family over a 1 year period. The changes
      were then subject to a validation process using convenient samples of patients
      from the author's multidoctor practice in Australia. Reliability was examined by
      the test-re-test method. Inter-rater reliability could not be assessed.
      Responsiveness was measured by measuring changes in score in the years before and
      after four events: counselling for a minor mental health problem; referral to a
      psychiatrist; diagnosis and treatment of breast cancer; and the occurrence of an
      acute myocardial infarction. RESULTS: The modifications made to the DUSOI have
      not altered the face or content validity of the original instrument. Construct
      validity and test-re-test reliability were satisfactory. Inter-rater reliability
      was not tested, but the original single patient score showed levels lower than
      are desirable. Responsiveness varied significantly. Families where a member was
      referred to a psychiatrist showed a decrease in burden after referral, while
      families where a member suffered an infarct showed a large increase. The other
      family groups did not show any change. CONCLUSION: A Family DUSOI will be of
      value in research when validated for individual conditions.

PMID- 15249536
TI  - The impact of diabetic retinopathy: perspectives from patient focus groups.
AB  - BACKGROUND: Diabetic retinopathy (DR) affects 50-85% of people with diabetes and
      may result in visual impairment or blindness. OBJECTIVE: This exploratory
      qualitative research was conducted to evaluate the symptom experience of DR, its
      impact on daily activities and health-related quality of life (HRQL), and the
      applicability of two vision-specific questionnaires. METHODS: Four focus groups
      (n = 15) were conducted with people with DR to explore their symptom experience
      and the impact on functioning and HRQL. Adults with type I or II diabetes and
      mild, moderate or severe non-proliferative DR (NPDR) or proliferative DR (PDR)
      were recruited. Content analysis and descriptive statistics were used to analyse
      the data. RESULTS: Participants described a range of symptoms and impact.
      Difficulty driving, especially at night, and trouble reading were noted with all
      levels of severity. Participants with PDR and decreased visual acuity have
      foregone many other important life aspects such as work, reading and sports. For
      the severely affected, diabetic care activities (e.g. exercising, reading
      nutritional labels, preparing insulin injections and glucose testing) were
      difficult to accomplish. Loss of independence, especially mobility and increased
      fear of accidents, had a profound impact on social activities. For those patients
      who had not experienced other complications of diabetes, the threat of vision
      loss was the most devastating. CONCLUSION: The loss of independence and mobility
      associated with decreased visual functioning and visual loss were major concerns.
      Moderate, severe NPDR and PDR associated with visual impairment have a
      significant impact on HRQL, particularly in the areas of independence, mobility,
      leisure and self-care activities.

PMID- 15249537
TI  - Health-related quality of life in carers of patients with dementia.
AB  - BACKGROUND: Carers of patients with dementia experience high levels of stress
      that can adversely affect their health and well-being. OBJECTIVE: Our aim was to
      assess the health-related quality of life of carers of patients with dementia
      compared with an age- and gender-matched sample from the general population.
      METHODS: A cross-sectional study was conducted in 37 primary health care centres
      in Catalonia, Spain. Carers (n = 181; 78% females, mean age 63 years) of patients
      with dementia together with a random sample of 543 individuals from the general
      population, matched for age and gender, were assessed with the SF-36
      questionnaire, which is a generic measure of health status. RESULTS: With the
      exception of physical function category, seven of the scales showed lower scores
      for females in the carer group. The most important differences were observed in
      the emotional role [95% confidence interval (CI) -37.7 to -3.6], mental health
      (95% CI -21.0 to -1.6) and bodily pain (95% CI -37.7 to -8.6) categories. In
      contrast, male carers had higher scores in the physical function category (95% CI
      2.2-19.4), and no differences were observed on the other scales. CONCLUSION:
      Female carers of patients with dementia experienced a seriously decreased quality
      of life level compared with their contemporaries in the general population.

PMID- 15249538
TI  - Quality, core values and the general practice consultation: issues of definition,
      measurement and delivery.

PMID- 15249539
TI  - TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo.
AB  - Factors influencing the development of CD4+CD25+ T-cells in vivo are poorly
      understood. In order to investigate the contribution of TGFbeta1 to the
      development and function of CD4+CD25+ T-cells, we generated a gain of function
      mutation resulting in the overexpression of an active form of TGFbeta1 in T-cells
      under control of the human CD2 promoter. In peripheral lymphoid organs and in the
      thymus, the frequency of CD4+CD25+ T-cells was increased in transgenic mice. This
      appeared to be due to an autocrine effect of TGFbeta on T-cells, since
      concomitant impairment of TGFbeta-signaling in double transgenic mice resulted in
      a phenotype similar to wild type. In contrast, in single transgenic mice with
      impaired TGFbeta-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in
      peripheral lymphoid organs but not in the thymus. In addition, TGFbeta was found
      to regulate the expression of Foxp3 in vivo, a transcription factor essential for
      the generation and function of regulatory T-cells. In CD4+CD25+ T-cells, TGFbeta1
      increased the expression of Foxp3, whereas a decreased expression was seen in
      CD4+CD25+ T-cells with impaired TGFbeta-signaling. TGFbeta1 induced the
      expression of IL-10 in transgenic T-cells, but the increased in vitro suppressive
      capacity observed in transgenic CD4+CD25+ T-cells was due to the secretion of
      TGFbeta and not IL-10. Therefore, our study provides in vivo evidence for a role
      of TGFbeta in the homeostasis of CD4+CD25+ T-cells.

PMID- 15249540
TI  - Endomucin, a sialomucin expressed in high endothelial venules, supports L
      selectin-mediated rolling.
AB  - Lymphocyte homing to lymph nodes is regulated by transient but specific
      interactions between lymphocytes and high endothelial venules (HEVs), the initial
      phase of which is mainly governed by the leukocyte adhesion molecule L-selectin,
      which recognizes sulfated and sialylated O-linked oligosaccharides displayed on
      sialomucin core proteins. One of the sialomucin proteins, endomucin, is
      predominantly expressed in vascular endothelial cells of a variety of tissues
      including the HEVs of lymph nodes; however, whether it functions as a ligand for
      L-selectin remains to be formally proven. Here we show that the endomucin splice
      isoform a is predominantly expressed in PNAd+ HEVs and MAdCAM-1+ HEVs, as seen in
      non-HEV-type vascular endothelial cells. Using affinity purification with soluble
      L-selectin, we found that HEV endomucin is specifically modified with L-selectin
      reactive oligosaccharides and can bind L-selectin as well as an HEV-specific mAb,
      MECA-79. Our results also indicated that a 90-100 kDa endomucin species is
      preferentially decorated with L-selectin-reactive sugar chains, whereas an 80 kDa
      species represents conventional forms expressed in non-HEV-type vascular
      endothelial cells in lymph nodes. Furthermore, a CHO cell line expressing
      endomucin together with a specific combination of carbohydrate-modifying enzymes
      [core-2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT), alpha-1,3
      fucosyltransferase VII (FucTVII) and L-selectin ligand sulfotransferase (LSST)]
      showed L-selectin-dependent rolling under flow conditions in vitro. These results
      suggest that when endomucin is appropriately modified by a specific set of
      glycosyltransferases and a sulfotransferase, it can function as a ligand for L
      selectin, and that the endomucin expressed in HEVs may represent another
      sialomucin ligand for L-selectin.

PMID- 15249541
TI  - Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic
      mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing
      endogenous murine MHC class II molecules.
AB  - Transgenic mice expressing human HLA class II molecules provide a useful model
      for identifying HLA-restricted CD4+ epitopes. However, the influence of
      endogenous murine H-2-restricted T cell responses on HLA-restricted responses is
      not known. In the present study, we show that HLA-DR1 transgenic mice deficient
      for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent
      expression level of the transgene HLA-DR1 and a similar diversity in the TCR
      repertoire, but a slightly different number of CD4+ peripheral T cells, when
      compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained
      (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1
      restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice
      immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak
      HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the
      immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2
      restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in
      HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of
      endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted
      antigen-specific responses in transgenic mice, by favoring murine over human MHC
      recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better
      model for identifying and characterizing HLA-DR1-restricted epitopes relevant for
      human disease.

PMID- 15249543
TI  - Bradykinin regulates cyclooxygenase-2 in rat renal thick ascending limb cells.
AB  - Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick
      ascending limb cells in the cortex and medulla and increases when the renin
      angiotensin and kallikrein-kinin systems are activated. Although the contribution
      of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin
      on COX-2 expression have not been determined in this nephron segment. We
      evaluated expression of B2 bradykinin receptors in thick ascending limb cells
      containing COX-2 and the effect of bradykinin on COX-2 expression in primary
      cultured medullary thick ascending cells. The presence of B2 receptors was
      studied in renal sections by immunohistochemistry with antibodies against B2, COX
      2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and
      basolateral portion of the thick ascending cells. These cells also contained COX
      2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation
      of cultured medullary thick ascending cells with bradykinin (10(-7) to 10(-5)
      mol/L) induced a significant increase on COX-2 protein expression. Maximal
      expression of COX-2 was observed 4 hours after exposure to bradykinin (10(-7)
      mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10(-6) mol/L).
      Prostaglandin E2 production increased when these cells were challenged with
      bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have
      demonstrated (1) the presence of B2 receptors in thick ascending limb cells
      expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein
      expression, via B2 receptors, in cultured medullary thick ascending cells. We
      suggest that bradykinin can affect ion transport in the thick ascending limb via
      a COX-2-mediated mechanism.

PMID- 15249544
TI  - Effect of angiotensin-converting enzyme inhibition on survival in 3773 Chinese
      type 2 diabetic patients.
AB  - We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on
      survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2
      diabetic patients with varying degree of albuminuria, ranging from
      normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2
      diabetic patients were followed prospectively for a mean period of 35.8 months.
      Clinical end points included all-cause mortality, with cardiovascular end point
      defined as first hospitalization because of ischemic heart disease, congestive
      heart failure, revascularization procedures, or cerebrovascular accident as well
      as renal end point defined as dialysis, doubling of baseline plasma creatinine,
      or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in
      normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in
      macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause
      mortality with 4-fold difference between NA and MA patients. The 7-year
      cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA
      groups, respectively. The use of ACE inhibition was associated with significant
      reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29,
      0.58) in the entire group and was most evident in high-risk patients who had
      cardiorenal complications or retinopathy at baseline for all albuminuric groups
      (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The
      prognostic value of albuminuria for death in type 2 diabetes and the beneficial
      effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or
      macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2
      diabetic patients with normoalbuminuria require further evaluation.

PMID- 15249545
TI  - Shear stress and flow-mediated dilation.

PMID- 15249546
TI  - Blood pressure, resting energy expenditure, and creatine kinase activity.

PMID- 15249547
TI  - Local shear stress and brachial artery flow-mediated dilation: the Framingham
      Heart Study.
AB  - Endothelium-dependent flow-mediated dilation is a homeostatic response to short
      term increases in local shear stress. Flow-mediated dilation of the brachial
      artery in response to postischemic reactive hyperemia is impaired in patients
      with cardiovascular disease risk factors and may reflect local endothelial
      dysfunction in the brachial artery. However, previous studies have largely
      neglected the effect of risk factors on evoked shear stress, which is the
      stimulus for dilation. We evaluated brachial artery percent dilation and evoked
      diastolic shear stress during reactive hyperemia using high-resolution ultrasound
      and Doppler in 2045 participants (1107 women, mean age 61 years) in the
      Framingham Offspring Study. In age- and sex-adjusted models, baseline and
      hyperemic shear stress were related to brachial artery percent dilation. In
      stepwise multivariable analyses examining clinical correlates of percent dilation
      (without shear stress in the model), age, sex, mean arterial pressure, pulse
      pressure, heart rate, body mass index, lipid medication use, and hormone
      replacement therapy were related to percent dilation (R2=0.189; P<0.001). When
      hyperemic shear stress was incorporated, the overall R2 improved (R2=0.335;
      P<0.001), but relationships between risk factors and percent dilation were
      attenuated (age and mean arterial pressure) or no longer significant (all
      others). In contrast, risk factors were related to baseline and hyperemic shear
      stress in multivariable analyses. Evoked hyperemic shear stress is a major
      correlate of brachial artery flow-mediated dilation. The associations between
      many risk factors and brachial artery flow-mediated dilation may be attributable
      to reduced stimulus for dilation rather than impaired local conduit artery
      response during hyperemia.

PMID- 15249548
TI  - Impaired endothelial release of tissue-type plasminogen activator in patients
      with chronic kidney disease and hypertension.
AB  - We have shown that the capacity for local release of tissue-type plasminogen
      activator (tPA) from the vascular endothelium is impaired in patients with
      primary hypertension. Because this response is an important protective mechanism
      against intravascular clotting, we investigated whether this system is also
      defective in patients with advanced chronic kidney disease and hypertension. Nine
      nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration
      rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age
      matched healthy controls. Intraarterial infusions of desmopressin, methacholine,
      and sodium nitroprusside were given locally in the brachial artery. Forearm blood
      flow was measured by venous occlusion plethysmography and blood collected
      repeatedly during the desmopressin infusion for determination of stimulated net
      and total cumulated release of tPA. The maximal release rate of active tPA
      (P<0.05) and the capacity for acute tPA release were markedly impaired in the
      renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly,
      the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue,
      respectively (P<0.05). However, there were no significant differences in
      vasodilator responses between the groups. Thus, patients with advanced chronic
      kidney disease and hypertension have a markedly impaired capacity for acute
      release of tissue plasminogen activator, despite preserved endothelium-dependent
      vasodilation. This defect may contribute to a defective local defense against
      arterial thrombosis.

PMID- 15249549
TI  - Mediastinal fat, insulin resistance, and hypertension.

PMID- 15249550
TI  - Trial of Preventing Hypertension (TROPHY): design and 2-year progress report.

PMID- 15249551
TI  - Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in
      pregnant but not nonpregnant mice.
AB  - Increased homocysteine is associated with the pregnancy complication preeclampsia
      and with later-life cardiovascular disease. Although elevated homocysteine
      persists after pregnancy, the vascular changes of preeclampsia abate with
      delivery, and cardiovascular disease occurs decades later. This suggests the
      vasculature during pregnancy may manifest increased sensitivity to homocysteine.
      We used the cystathionine-beta synthase (CBS)-deficient transgenic mouse to
      investigate whether hyperhomocysteinemia would differentially affect vascular
      function in nonpregnant and pregnant animals. Mesenteric arteries from
      nonpregnant and midpregnant (14 to 16 days) wild-type, heterozygous, and
      homozygous CBS-deficient transgenic mice were investigated for their response to
      vasoconstriction, endothelial-dependent, and endothelial-independent relaxation
      using an isometric wire myograph system. Endothelial-dependent vasodilation was
      similar in arteries from nonpregnant heterozygous and wild-type mice. In
      contrast, endothelial-dependent relaxation was reduced significantly in arteries
      from pregnant heterozygous animals compared with wild-type mice. Inhibition of NO
      synthesis blunted relaxation in arteries from pregnant wild-type but not pregnant
      heterozygous mice. Endothelial-dependent relaxation was restored by in vitro
      pretreatment with the tetrahydrobiopterin precursor sepiapterin. These data
      indicate that in pregnant mice, endothelial-dependent vasodilation is more
      sensitive to the effect of increased homocysteine than arteries from nonpregnant
      mice. This effect appears to result from a loss in NO-mediated relaxation that
      may be mediated by the oxidative inactivation of the NO synthase cofactor
      tetrahydrobiopterin.

PMID- 15249552
TI  - Joining mutants of RAG1 and RAG2 that demonstrate impaired interactions with the
      coding-end DNA.
AB  - In V(D)J joining of antigen receptor genes, two recombination signal sequences
      (RSSs), 12- and 23-RSSs, form a complex with the protein products of
      recombination activating genes, RAG1 and RAG2. DNaseI footprinting demonstrates
      that the interaction of RAG proteins with substrate RSS DNA is not just limited
      to the signal region but involves the coding sequence as well. Joining mutants of
      RAG1 and RAG2 demonstrate impaired interactions with the coding region in both
      pre- and postcleavage type complexes. A possible role of this RAG coding region
      interaction is discussed in the context of V(D)J recombination.

PMID- 15249553
TI  - Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy
      5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase.
AB  - Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises
      oxidized purines such as 7,8-dihydro-8-oxoguanine (8-oxoG) and 2,6-diamino-4
      hydroxy-5-formamidopyrimidine (FapyG) from damaged DNA. Here, we report the
      crystal structure of the Fpg protein from Lactococcus lactis (LlFpg) bound to a
      carbocyclic FapydG (cFapydG)-containing DNA. The structure reveals that Fpg
      stabilizes the cFapydG nucleoside into an extrahelical conformation inside its
      substrate binding pocket. In contrast to the recognition of the 8-oxodG lesion,
      which is bound with the glycosidic bond in a syn conformation, the cFapydG lesion
      displays in the complex an anti conformation. Furthermore, Fpg establishes
      interactions with all the functional groups of the FapyG base lesion, which can
      be classified in two categories: (i) those specifying a purine-derived lesion
      (here a guanine) involved in the Watson-Crick face recognition of the lesion and
      probably contributing to an optimal orientation of the pyrimidine ring moiety in
      the binding pocket and (ii) those specifying the imidazole ring-opened moiety of
      FapyG and probably participating also in the rotameric selection of the FapydG
      nucleobase. These interactions involve strictly conserved Fpg residues and
      structural water molecules mediated interactions. The significant differences
      between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into
      the Fpg substrate specificity.

PMID- 15249554
TI  - A piece of my mind. Baby Mo: a letter from Vietnam.

PMID- 15249555
TI  - Conquering HIV and stigma in Kenya.

PMID- 15249556
TI  - Small loans yield big health profits.

PMID- 15249557
TI  - Thousands fall through HIV treatment gap: IOM wants new federal program.

PMID- 15249558
TI  - Report: HIV prevention efforts remain crucial as global treatment access expands.

PMID- 15249561
TI  - Strategies to diagnose and treat group A streptococcal pharyngitis.

PMID- 15249562
TI  - Pharmacological treatment of delirium in the intensive care unit.

PMID- 15249563
TI  - Risk-treatment paradox in use of statins.

PMID- 15249564
TI  - On-pump vs off-pump coronary artery bypass grafting.

PMID- 15249565
TI  - Fee-for-service vs managed care medicine.

PMID- 15249566
TI  - Efficacy of an HIV prevention intervention for African American adolescent girls:
      a randomized controlled trial.
AB  - CONTEXT: African American adolescent girls are at high risk for human
      immunodeficiency virus (HIV) infection, but interventions specifically designed
      for this population have not reduced HIV risk behaviors. OBJECTIVE: To evaluate
      the efficacy of an intervention to reduce sexual risk behaviors, sexually
      transmitted diseases (STDs), and pregnancy and enhance mediators of HIV
      preventive behaviors. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled
      trial of 522 sexually experienced African American girls aged 14 to 18 years
      screened from December 1996 through April 1999 at 4 community health agencies.
      Participants completed a self-administered questionnaire and an interview,
      demonstrated condom application skills, and provided specimens for STD testing.
      Outcome assessments were made at 6- and 12-month follow-up. INTERVENTION: All
      participants received four 4-hour group sessions. The intervention emphasized
      ethnic and gender pride, HIV knowledge, communication, condom use skills, and
      healthy relationships. The comparison condition emphasized exercise and
      nutrition. MAIN OUTCOME MEASURES: The primary outcome measure was consistent
      condom use, defined as condom use during every episode of vaginal intercourse;
      other outcome measures were sexual behaviors, observed condom application skills,
      incident STD infection, self-reported pregnancy, and mediators of HIV-preventive
      behaviors. RESULTS: Relative to the comparison condition, participants in the
      intervention reported using condoms more consistently in the 30 days preceding
      the 6-month assessment (unadjusted analysis, intervention, 75.3% vs comparison,
      58.2%) and the 12-month assessment (unadjusted analysis, intervention, 73.3% vs
      comparison, 56.5%) and over the entire 12-month period (adjusted odds ratio,
      2.01; 95% confidence interval [CI], 1.28-3.17; P =.003). Participants in the
      intervention reported using condoms more consistently in the 6 months preceding
      the 6-month assessment (unadjusted analysis, intervention, 61.3% vs comparison,
      42.6%), at the 12-month assessment (unadjusted analysis, intervention, 58.1% vs
      comparison, 45.3%), and over the entire 12-month period (adjusted odds ratio,
      2.30; 95% CI, 1.51-3.50; P<.001). Using generalized estimating equation analyses
      over the 12-month follow-up, adolescents in the intervention were more likely to
      use a condom at last intercourse, less likely to have a new vaginal sex partner
      in the past 30 days, and more likely to apply condoms to sex partners and had
      better condom application skills, a higher percentage of condom-protected sex
      acts, fewer unprotected vaginal sex acts, and higher scores on measures of
      mediators. Promising effects were also observed for chlamydia infections and self
      reported pregnancy. CONCLUSION: Interventions for African American adolescent
      girls that are gender-tailored and culturally congruent can enhance HIV
      preventive behaviors, skills, and mediators and may reduce pregnancy and
      chlamydia infection.

PMID- 15249567
TI  - Efficacy and safety of emtricitabine vs stavudine in combination therapy in
      antiretroviral-naive patients: a randomized trial.
AB  - CONTEXT: Emtricitabine is a new, once-daily nucleoside reverse transcriptase
      inhibitor (NRTI) with potent activity against human immunodeficiency virus (HIV).
      OBJECTIVE: To assess the efficacy and safety of emtricitabine as compared with
      stavudine when used with a background regimen of didanosine and efavirenz.
      DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, double-dummy study
      conducted at 101 research clinics in North America, Latin America, and Europe.
      The first patient was enrolled on August 21, 2000; no investigator or patient was
      unblinded until the last patient randomized completed the week 48 visit on
      October 24, 2002. Analyses were based on data collected in a double-blind setting
      with a median follow-up of 60 weeks. Patients were 571 antiretroviral-naive, HIV
      1-infected adults aged 18 years or older with viral load levels greater than or
      equal to 5000 copies/mL. INTERVENTIONS: Receipt of either 200 mg of emtricitabine
      once daily (plus stavudine placebo twice daily) (n = 286) or stavudine at
      standard doses twice daily (plus emtricitabine placebo once daily) (n = 285) plus
      open-label didanosine and efavirenz, once daily. MAIN OUTCOME MEASURE: Persistent
      virological response, defined as achieving and maintaining viral load at or below
      the limit of assay quantification (< or =400 or 50 copies/mL). RESULTS: At the
      interim analysis on June 14, 2002, when the last patient randomized completed 24
      weeks of double-blind treatment (median follow-up time of 42 weeks), patients in
      the emtricitabine group had a higher probability of a persistent virological
      response < or =50 copies/mL vs the stavudine group (85% vs 76%, P =.005). This
      was associated with a higher mean CD4 cell count change from baseline for the
      emtricitabine group (156 cells/ microL vs 119 cells/microL, P =.01 [of note,
      there was no statistical difference at 48 weeks [P =.15], although a sensitivity
      analysis, using an intent-to-treat population with the last CD4 cell count
      observation carried forward to week 48 showed a difference [P =.02]]). The
      independent data and safety monitoring board recommended offering open-label
      emtricitabine based on the interim analysis. The probability of persistent
      virological response < or =50 copies/mL through week 60 was 76% for the
      emtricitabine group vs 54% for the stavudine group (P<.001). The probability of
      virological failure through week 60 was 4% in the emtricitabine group and 12% in
      the stavudine group (P<.001). Patients in the stavudine group had a greater
      probability of an adverse event that led to study drug discontinuation through
      week 60 than did those in the emtricitabine group (15% vs 7%, P =.005).
      CONCLUSION: Once-daily emtricitabine appeared to demonstrate greater virological
      efficacy, durability of response, and tolerability compared with twice-daily
      stavudine when used with once-daily didanosine and efavirenz.

PMID- 15249568
TI  - Efficacy and safety of tenofovir DF vs stavudine in combination therapy in
      antiretroviral-naive patients: a 3-year randomized trial.
AB  - CONTEXT: Tenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue
      reverse transcriptase inhibitor. OBJECTIVE: To evaluate the efficacy and safety
      of tenofovir DF compared with stavudine in antiretroviral-naive patients. DESIGN,
      SETTING, AND PARTICIPANTS: A prospective, randomized, double-blind study
      conducted at 81 centers in the United States, South America, and Europe from June
      9, 2000, to January 30, 2004. A total of 753 patients infected with HIV who were
      antiretroviral naive were screened and 602 patients entered the study.
      INTERVENTION: Patients were randomized to receive either tenofovir DF (n = 299)
      or stavudine (n = 303), with placebo, in combination with lamivudine and
      efavirenz. MAIN OUTCOME MEASURE: Proportion of patients with HIV RNA levels of
      less than 400 copies/mL at week 48. RESULTS: In the primary intent-to-treat
      analysis in which patients with missing data or who added or switched
      antiretroviral medications before week 48 were considered as failures, the
      proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239
      (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients
      receiving stavudine (95% confidence interval, -10.4% to 1.5%), exceeding the
      predefined -10% limit for equivalence. However, equivalence was demonstrated in
      the secondary analyses (HIV RNA <50 copies/mL) at week 48 and through 144 weeks.
      Virologic failure was associated most frequently with efavirenz and lamivudine
      resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in
      the tenofovir DF and stavudine groups, respectively (P =.06). A more favorable
      mean change from baseline in fasting lipid profile was noted in the tenofovir DF
      group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n = 170]
      vs +134 mg/dL for stavudine [n = 162], P<.001), total cholesterol (+30 mg/dL [n =
      170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol
      (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], P<.001), and high-density
      lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P =.003).
      Investigator-reported lipodystrophy was less common in the tenofovir DF group
      compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, P<.001). The
      number of bone fractures and the renal safety profile were similar between the 2
      groups. CONCLUSIONS: Through 144 weeks, the combination of tenofovir DF,
      lamivudine, and efavirenz was highly effective and comparable with stavudine,
      lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF
      appeared to be associated with better lipid profiles and less lipodystrophy.

PMID- 15249569
TI  - Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an
      African setting: a randomized controlled trial.
AB  - CONTEXT: Antenatal counseling and human immunodeficiency virus (HIV) testing are
      not universal in Africa; thus, women often present in labor with unknown HIV
      status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral
      dose of NVP to the mother at the start of labor and to the infant within 72 hours
      of birth). OBJECTIVE: To determine risk of mother-to-child transmission of HIV
      when either standard use of NVP alone or in combination with zidovudine (ZDV) was
      administered to infants of women tested at delivery. DESIGN, SETTING, AND
      PARTICIPANTS: A randomized, open-label, phase 3 trial conducted between April 1,
      2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial
      included all infants born to 894 women who were HIV positive, received NVP
      intrapartum, and were previously antiretroviral treatment-naive. Infants were
      randomly assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were
      enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18
      months. The HIV status of 90% of all infants was established at 6 to 8 weeks.
      INTERVENTION: Mothers received a 200-mg single oral dose of NVP intrapartum and
      infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg
      of ZDV twice per day for a week. MAIN OUTCOME MEASURES: HIV infection of infant
      at birth and 6 to 8 weeks, and adverse events. RESULTS: The mother-to-child
      transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only
      and 10.1% (45/444) in those administered NVP plus ZDV (P =.30). A life table
      estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [CI],
      10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those
      who received NVP plus ZDV (P =.36). For infants not infected at birth and
      retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received
      NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P =.88). Almost
      all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4
      adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants
      receiving NVP only and NVP plus ZDV, respectively (P =.76). CONCLUSIONS: The
      frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study
      groups was comparable with that observed for other perinatal HIV intervention
      studies among breastfeeding women in Africa. The safety of the regimen containing
      neonatal ZDV was similar to that of a standard NVP regimen.

PMID- 15249570
TI  - Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a
      randomized controlled trial.
AB  - CONTEXT: Reduced growth hormone (GH) concentrations are observed in men with
      human immunodeficiency virus (HIV) lipodystrophy. OBJECTIVE: To investigate the
      effects of growth hormone-releasing hormone (GHRH), a GH secretagogue, in
      treatment of HIV lipodystrophy. DESIGN, SETTING, AND PARTICIPANTS: Randomized,
      double-blind, placebo-controlled trial conducted at a research center in the
      United States between October 2002 and June 2003 and enrolling 31 HIV-infected
      men aged 18 to 60 years with evidence of lipodystrophy. INTERVENTIONS:
      Participants were assigned to receive GHRH (1 mg subcutaneously twice daily) or
      placebo for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in
      concentrations of insulin-like growth factor 1 (IGF-1) to detect overall change
      in GH levels in response to GHRH. Secondary end points included body composition
      by dual-energy x-ray absorptiometry and computed tomography, lipodystrophy
      ratings, and levels of glucose, insulin, and lipids. RESULTS: Mean (SD) IGF-1
      concentrations increased significantly in the GHRH group vs the placebo group
      (104 [110] ng/mL vs 6 [44] ng/mL, P =.004). Lean body mass significantly
      increased in the GHRH group vs the placebo group (0.9 [1.3] kg vs -0.3 [1.7] kg,
      P =.04), trunk fat significantly decreased (-0.4 [0.7] kg vs 0.2 [0.6] kg, P
      =.03), and the ratio of trunk to lower extremity fat improved significantly (
      0.22 [0.32] vs 0.14 [0.29], P =.005). Abdominal visceral fat was reduced (-19.2
      [36.6] cm2 vs 2.3 [24.3] cm2, P =.07) and the ratio of abdominal visceral fat to
      abdominal subcutaneous fat improved significantly more in the GHRH group (-0.19
      [0.28] vs 0.07 [0.27], P =.02). Both physician and patient rating of
      lipodystrophy in the arms, legs, and abdomen also improved significantly. Levels
      of glucose, insulin, and lipids did not change significantly. CONCLUSIONS: GHRH
      was well tolerated and effectively increased levels of IGF-1 in HIV-infected men
      with lipodystrophy. Total and regional body composition improved in response to
      GHRH, with increased lean mass and reduced truncal and visceral fat. Use of GHRH
      may potentially be a beneficial treatment strategy for this population.

PMID- 15249571
TI  - Rapid HIV-1 testing during labor: a multicenter study.
AB  - CONTEXT: Timely testing of women in labor with undocumented human
      immunodeficiency virus (HIV) status could enable immediate provision of
      antiretroviral prophylaxis. OBJECTIVES: To determine the feasibility and
      acceptance of rapid HIV testing among women in labor and to assess rapid HIV
      assay performance. DESIGN, SETTING, AND PATIENTS: The Mother-Infant Rapid
      Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and
      voluntary rapid HIV testing for women in labor at 16 US hospitals from November
      16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood
      was used. MAIN OUTCOME MEASURES: Acceptance of HIV testing; sensitivity,
      specificity, and predictive value of the rapid test; time from blood collection
      to patient notification of results. RESULTS: There were 91,707 visits to the
      labor and delivery units in the study, 7381 of which were by eligible women
      without documentation of HIV testing. Of these, 5744 (78%) women were approached
      for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive
      for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test
      were 100% and 99.9%, respectively; positive predictive value was 90% compared
      with 76% for enzyme immunoassay (EIA). Factors independently associated with
      higher test acceptance included younger age, being black or Hispanic, gestational
      age less than 32 weeks, and having had no prenatal care. Lower acceptance was
      associated with being admitted between 4 pm and midnight, particularly on Friday
      nights, but this may be explained in part by fewer available personnel. Median
      time from blood collection to patient notification of result was 66 minutes
      (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001).
      CONCLUSIONS: Rapid HIV testing is feasible and delivers accurate and timely test
      results for women in labor. It provides HIV-positive women prompt access to
      intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal
      HIV transmission, and may be particularly applicable to higher-risk populations.

PMID- 15249572
TI  - Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic
      review.
AB  - CONTEXT: Evidence suggests that since highly active antiretroviral therapy
      (HAART) became available, the prevalence of unprotected sex and the incidence of
      sexually transmitted infections (STIs) have increased. OBJECTIVE: To conduct 3
      meta-analyses to determine whether (1) being treated with HAART, (2) having an
      undetectable viral load, or (3) holding specific beliefs about HAART and viral
      load are associated with increased likelihood of engaging in unprotected sex.
      DATA SOURCES: A comprehensive search included electronic bibliographic databases,
      including AIDSLINE, MEDLINE, PubMed, CINHAL, PsycInfo, ERIC, EMBASE, and
      Sociofile, from January 1996 to August 2003, conference proceedings, hand
      searches of journals, reference lists of articles, and contacts with researchers.
      STUDY SELECTION: Twenty-five English-language studies (some contributing >1
      finding) met the selection criteria and examined the association of unprotected
      sexual intercourse or STIs with receiving HAART (21 findings), having an
      undetectable viral load (13 findings), or beliefs about HAART and viral load (18
      findings). DATA EXTRACTION: Reports were screened and information from eligible
      studies was abstracted independently by pairs of reviewers using a standardized
      spreadsheet. DATA SYNTHESIS: Random-effects models were used to aggregate data.
      The prevalence of unprotected sex was not higher among persons with the human
      immunodeficiency virus (HIV) receiving HAART (prevalence range, 9%-56%; median,
      33%) vs those not receiving HAART (range, 11%-77%; median, 44%; odds ratio [OR],
      0.92; 95% confidence interval [CI], 0.65-1.31) or among HIV-positive persons with
      an undetectable viral load (range, 10%-68%; median, 39%) vs those with a
      detectable viral load (range, 14%-70%; median, 42%; OR, 0.99; 95% CI, 0.82-1.21).
      The prevalence of unprotected sex was elevated (OR, 1.82; 95% CI, 1.52-2.17) in
      HIV-positive, HIV-negative, and unknown serostatus persons who believed that
      receiving HAART or having an undetectable viral load protects against
      transmitting HIV or who had reduced concerns about engaging in unsafe sex given
      the availability of HAART (range, 17%-81% [median, 49%] vs 9%-68% [median, 38%]
      for counterparts). CONCLUSIONS: In the studies reviewed, HIV-positive patients
      receiving HAART did not exhibit increased sexual risk behavior, even when therapy
      achieved an undetectable viral load. However, people's beliefs about HAART and
      viral load may promote unprotected sex and may be amenable to change through
      prevention messages.

PMID- 15249573
TI  - Clinical trials in sub-Saharan Africa and established standards of care: a
      systematic review of HIV, tuberculosis, and malaria trials.
AB  - CONTEXT: The minimum standard of care required for participants in clinical
      trials conducted in resource-poor settings is a matter of controversy;
      international documents offer contradictory guidance. OBJECTIVE: To determine
      whether recently published trials conducted in sub-Saharan Africa met standards
      of care consistent with best current clinical standards for human
      immunodeficiency virus (HIV) treatment, tuberculosis treatment, and malaria
      prevention. DATA SOURCES: Trials published during or after January 1998 that were
      indexed at the time of the MEDLINE and Cochrane Controlled Trials Register Search
      (November 20, 2003). STUDY SELECTION: All randomized clinical trials that were
      conducted in sub-Saharan Africa in 3 clinical domains: HIV disease, tuberculosis
      treatment, and malaria prophylaxis. DATA EXTRACTION: To establish criteria for
      best current standards of care, evidence from the literature and published
      guidelines accepted for well-resourced settings were analyzed; the actual care
      offered in the trial was then compared with these standards. DATA SYNTHESIS: A
      total of 128 eligible articles described data from 73 different randomized
      clinical trials. Only 12 trials (16%) provided care that met guidelines to both
      intervention and control patients. Only 1 of the 34 trials that enrolled patients
      with HIV disease provided antiretroviral treatment that conformed to guidelines.
      Conversely, all tuberculosis treatment trials (n = 13, including 3 for HIV
      infected patients) provided tuberculosis therapy that conformed to guidelines.
      Twenty-one (72%) of 29 malaria prophylaxis trials tested interventions that met
      guidelines, but only 3 (10%) used any active prophylactic intervention in the
      control group. Of the 59 trials (81%) that reported on the process of ethical
      review, all were reviewed by a host African institution and 64% were additionally
      reviewed by an institution in a developed country. CONCLUSIONS: Rates of
      adherence to established clinical guidelines of care in randomized clinical
      trials of HIV treatment, tuberculosis treatment, and malaria prophylaxis varied
      considerably between disease categories. In determining clinical standards for
      trials in sub-Saharan Africa, researchers and ethics committees appear to take
      the local level of care into account.

PMID- 15249574
TI  - HIV Infection, hepatitis C infection, and HAART: hard clinical choices.
AB  - Abnormalities in hepatic function have become one of the most common
      complications occurring among human immunodeficiency virus (HIV)-infected
      individuals receiving highly active antiretroviral therapy (HAART), and liver
      disease has become an increasingly important cause of morbidity and mortality in
      HIV-infected patients. We present a case of a patient with HIV infection and
      hepatotoxicity that exemplifies the complications currently observed during the
      treatment of such patients. Hepatotoxicity can be a result of several factors,
      including a direct effect of HAART, substance abuse, and coinfection with either
      hepatitis C virus (HCV) or hepatitis B virus. Imaging studies may be helpful in
      determining the etiology; however, a liver biopsy is often necessary to be able
      to more accurately determine the relative contributions of different processes.
      Although coinfection with HCV and HIV has become a common clinical problem,
      optimal treatment of such patients remains to be defined and must be
      individualized to maximize benefit and tolerance.

PMID- 15249575
TI  - Treatment for adult HIV infection: 2004 recommendations of the International AIDS
      Society-USA Panel.
AB  - CONTEXT: Substantial changes in the field of human immunodeficiency virus (HIV)
      treatment have occurred in the last 2 years, prompting revision of the guidelines
      for antiretroviral management of adults with established HIV infection.
      OBJECTIVE: To update recommendations for physicians who provide HIV care
      regarding when to start antiretroviral therapy, what drugs to start with, when to
      change drug regimens, and what drug regimens to switch to after therapy fails.
      DATA SOURCES: Evidence was identified and reviewed by a 16-member noncompensated
      panel of physicians with expertise in HIV-related basic science and clinical
      research, antiretroviral therapy, and HIV patient care. The panel was designed to
      have broad US and international representation for areas with adequate access to
      antiretroviral management. STUDY SELECTION: Evidence considered included
      published basic science, clinical research, and epidemiological data (identified
      by experts in the field or extracted through MEDLINE searches using terms
      relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific
      conferences between July 2002 and May 2004. DATA EXTRACTION: Data were reviewed
      to identify any information that might change previous guidelines. Based on panel
      discussion, guidelines were drafted by a writing committee and discussed by the
      panel until consensus was reached. DATA SYNTHESIS: Four antiretroviral drugs
      recently have been made available and have broadened the options for initial and
      subsequent regimens. New data allow more definitive recommendations for specific
      drugs or regimens to include or avoid, particularly with regard to initial
      therapy. Recommendations are rated according to 7 evidence categories, ranging
      from I (data from prospective randomized clinical trials) to VII (expert opinion
      of the panel). CONCLUSION: Further insights into the roles of drug toxic effects,
      drug resistance, and pharmacological interactions have resulted in additional
      guidance for strategic approaches to antiretroviral management.

PMID- 15249576
TI  - Treatment of HIV/AIDS: do the dilemmas only increase?

PMID- 15249577
TI  - The long journey to health equity.

PMID- 15249578
TI  - JAMA patient page. HIV infection: the basics.

PMID- 15249579
TI  - Vav GEFs are required for beta2 integrin-dependent functions of neutrophils.
AB  - Integrin regulation of neutrophils is essential for appropriate adhesion and
      transmigration into tissues. Vav proteins are Rho family guanine nucleotide
      exchange factors that become tyrosine phosphorylated in response to adhesion.
      Using Vav1/Vav3-deficient neutrophils (Vav1/3ko), we show that Vav proteins are
      required for multiple beta2 integrin-dependent functions, including sustained
      adhesion, spreading, and complement-mediated phagocytosis. These defects are not
      attributable to a lack of initial beta2 activation as Vav1/3ko neutrophils
      undergo chemoattractant-induced arrest on intercellular adhesion molecule-1 under
      flow. Accordingly, in vivo, Vav1/3ko leukocytes arrest on venular endothelium yet
      are unable to sustain adherence. Thus, Vav proteins are specifically required for
      stable adhesion. beta2-induced activation of Cdc42, Rac1, and RhoA is defective
      in Vav1/3ko neutrophils, and phosphorylation of Pyk2, paxillin, and Akt is also
      significantly reduced. In contrast, Vav proteins are largely dispensable for G
      protein-coupled receptor-induced signaling events and chemotaxis. Thus, Vav
      proteins play an essential role coupling beta2 to Rho GTPases and regulating
      multiple integrin-induced events important in leukocyte adhesion and
      phagocytosis.

PMID- 15249580
TI  - A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast.
AB  - The mammalian tumor suppressor, phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating
      phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a
      homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This
      was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae)
      lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher
      eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly,
      upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels
      comparable to those in mammalian cells, indicating that a pathway exists for
      synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN,
      suppresses PI(3,4,5)P3 levels. By examining various mutants, we show that
      synthesis of PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3
      kinase, vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but
      does not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These
      studies suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class
      III phosphoinositide 3-kinase evolved before the appearance of class I
      phosphoinositide 3-kinases.

PMID- 15249581
TI  - Borealin: a novel chromosomal passenger required for stability of the bipolar
      mitotic spindle.
AB  - The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has
      essential regulatory roles at centromeres and the central spindle in mitosis.
      Here, we describe Borealin, a novel member of the complex. Approximately half of
      Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin; and
      Borealin binds Survivin and INCENP in vitro. A second complex contains Aurora B
      and INCENP, but no Borealin or Survivin. Depletion of Borealin by RNA
      interference delays mitotic progression and results in kinetochore-spindle
      misattachments and an increase in bipolar spindles associated with ectopic
      asters. The extra poles, which apparently form after chromosomes achieve a
      bipolar orientation, severely disrupt the partitioning of chromosomes in
      anaphase. Borealin depletion has little effect on histone H3 serine10
      phosphorylation. These results implicate the chromosomal passenger holocomplex in
      the maintenance of spindle integrity and suggest that histone H3 serine10
      phosphorylation is performed by an Aurora B-INCENP subcomplex.

PMID- 15249582
TI  - Closed chromatin loops at the ends of chromosomes.
AB  - The termini of eukaryotic chromosomes contain specialized protective structures,
      the telomeres, composed of TTAGGG repeats and associated proteins which, together
      with telomerase, control telomere length. Telomere shortening is associated with
      senescence and inappropriate telomerase activity may lead to cancer. Little is
      known about the chromatin context of telomeres, because, in most cells, telomere
      chromatin is tightly anchored within the nucleus. We now report the successful
      release of telomere chromatin from chicken erythrocyte and mouse lymphocyte
      nuclei, both of which have a reduced karyoskeleton. Electron microscopy reveals
      telomere chromatin fibers in the form of closed terminal loops, which correspond
      to the "t-loop" structures adopted by telomere DNA. The ability to recognize
      isolated telomeres in their native chromatin conformation opens the way for
      detailed structural and compositional studies.

PMID- 15249583
TI  - The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS
      proteins.
AB  - Insulin-like growth factors elicit many responses through activation of
      phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2)
      suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1),
      which generally requires PI3K signals for its activation. Here, we show that TSC1
      2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling
      to PI3K by restraining the activity of S6K, which when activated inactivates
      insulin receptor substrate (IRS) function, via repression of IRS-1 gene
      expression and via direct phosphorylation of IRS-1. Our results argue that the
      low malignant potential of tumors arising from TSC1-2 dysfunction may be
      explained by the failure of TSC mutant cells to activate PI3K and its downstream
      effectors.

PMID- 15249584
TI  - Phase III study of adjuvant chemotherapy and radiation therapy compared with
      chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of
      intergroup protocol 0130.
AB  - PURPOSE: Some patients with colon cancer have a high risk of local recurrence
      postoperatively. This trial was undertaken to determine whether radiation therapy
      added to an adjuvant chemotherapy regimen improves outcome in high-risk patients.
      PATIENTS AND METHODS: Patients with resected colon cancer with tumor adherence or
      invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending
      or descending colon were randomly assigned to receive fluorouracil and levamisole
      therapy with or without radiation therapy. Patients who received chemotherapy and
      radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions
      beginning 28 days after starting chemotherapy. Patient enrollment was terminated
      because of slow accrual after 222 patients enrolled (original goal was 700
      patients); 187 patients were assessable. RESULTS: Overall 5-year survival was 62%
      for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease
      free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred
      in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia
      (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT
      patients (P =.02). No significant difference in nonhematologic toxicity (>/=
      grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P
      =.26). CONCLUSION: Patients who received chemotherapy or chemoRT had similar
      overall survival and disease-free survival. Toxicity was higher among chemoRT
      patients. These results must be interpreted with caution because of the high
      number of ineligible patients and the limited power of the study to detect
      potentially meaningful differences.

PMID- 15249586
TI  - Assessing prognosis in non-small-cell lung cancer: avenues to a more complete
      picture?

PMID- 15249585
TI  - Upregulation of the tissue inhibitor of metalloproteinase-1 protein is associated
      with progression of human non-small-cell lung cancer.
AB  - PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring
      inhibitors of matrix metalloproteinases (MMPs). It has been shown that TIMP-1 may
      be a multifunctional protein. Little is known about the role of TIMP-1 in
      progression and metastasis of human lung cancer (tumor inhibiting or tumor
      promoting), although studies using a variety of techniques have analyzed the
      expression of TIMP-1 mRNA and/or protein in human cancers. PATIENTS AND METHODS:
      We examined the expression of TIMP-1 protein by immunohistochemistry in patients
      (n = 160) with primary respectable (stage I to IIIA) non-small-cell lung cancer
      (NSCLC). RESULTS: Twenty-seven percent of the tumors (43 of 160) demonstrated
      elevated expression of this protein. We demonstrate that overexpression of TIMP-1
      protein is associated with an adverse outcome. In addition, disease stage,
      patient's age, and performance status were all significantly related to survival.
      In multivariate analyses, patients with high TIMP-1 expression had a 90%
      increased risk of death when compared with those with low expression (relative
      risk, 1.92; 95% CI, 1.19 to 3.09; P =.008). TIMP-1 expression did not correlate
      with expression of MMP-2 and MMP-9. CONCLUSION: These results suggest that TIMP
      1, independent of its inhibiting activity of MMPs, may have other function(s)
      critical for NSCLCs. The significance of our results is two-fold. The adverse
      outcome in patients with overexpression of TIMP-1 indicates its potential
      prognostic value in NSCLC. Thus, TIMP-1 overexpression may serve to help identify
      patients with particularly aggressive disease for adjuvant treatments. In
      addition, the TIMP-1 molecule may represent a novel therapeutic target for
      treatment of some NSCLCs.

PMID- 15249587
TI  - Immunomodulatory analogs of thalidomide: an emerging new therapy in myeloma.

PMID- 15249588
TI  - Patient selection, realism, and randomized clinical trials.

PMID- 15249589
TI  - Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or
      refractory multiple myeloma.
AB  - PURPOSE: To assess the safety, efficacy, and immunomodulatory effects of CC-4047
      (Actimid; Celgene, San Diego, CA) in patients with relapsed or refractory
      myeloma. PATIENTS AND METHODS: Twenty-four relapsed or refractory patients were
      treated with a dose-escalating regimen of oral CC-4047. Clinical responses and
      adverse effects were identified, and peripheral T-cell subsets, serum cytokines,
      and proangiogenic factors were evaluated. RESULTS: CC-4047 was tolerated with no
      serious nonhematologic adverse events. All patients were eligible for analysis.
      Toxicity criteria during the initial 4 weeks of study were used to define the
      maximum-tolerated dose (MTD). During this period, one patient withdrew with a
      deep vein thrombosis (DVT) probably caused by an undiagnosed primary melanoma
      with lymphadenopathy in the groin, one patient withdrew because of progressive
      disease (PD), and three patients discontinued with neutropenia. Nineteen of 24
      patients continued on treatment beyond 4 weeks to PD or development of a serious
      adverse event. Three further patients developed a DVT at 4, 9, and 11 months.
      Treatment resulted in a greater than 25% reduction in paraprotein in 67% of
      patients, 13 patients (54%) experienced a greater than 50% reduction in
      paraprotein, and four (17%) of 24 patients entered complete remission. The MTD
      was 2 mg/d. All patients showed increased CD45RO expression on CD4(+) and CD8(+)
      cells, with a concomitant decrease in CD45RA(+) cells. CC-4047 treatment was
      associated with significantly increased serum interleukin (IL)-2 receptor and IL
      12 levels, which is consistent with activation of T cells and monocytes and
      macrophages. CONCLUSION: This study demonstrates the safety and efficacy of CC
      4047. The MTD of CC-4047 orally was 2 mg/d. This is the first report
      demonstrating in vivo T-cell costimulation by this class of compound, supporting
      a potential role for CC-4047 as an immunostimulatory adjuvant treatment.

PMID- 15249590
TI  - Large-scale identification of tubulin-binding proteins provides insight on
      subcellular trafficking, metabolic channeling, and signaling in plant cells.
AB  - Microtubules play an essential role in the growth and development of plants and
      are known to be involved in regulating many cellular processes ranging from
      translation to signaling. In this article, we describe the proteomic
      characterization of Arabidopsis tubulin-binding proteins that were purified using
      tubulin affinity chromatography. Microtubule co-sedimentation assays indicated
      that most, if not all, of the proteins in the tubulin-binding protein fraction
      possessed microtubule-binding activity. Two-dimensional gel electrophoresis of
      the tubulin-binding protein fraction was performed, and 86 protein spots were
      excised and analyzed for protein identification. A total of 122 proteins were
      identified with high confidence using LC-MS/MS. These proteins were grouped into
      six categories based on their predicted functions: microtubule-associated
      proteins, translation factors, RNA-binding proteins, signaling proteins,
      metabolic enzymes, and proteins with other functions. Almost one-half of the
      proteins identified in this fraction were related to proteins that have
      previously been reported to interact with microtubules. This study represents the
      first large-scale proteomic identification of eukaryotic cytoskeleton-binding
      proteins, and provides insight on subcellular trafficking, metabolic channeling,
      and signaling in plant cells.

PMID- 15249591
TI  - A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells.
AB  - Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic)
      stimuli underlie the pathology of physical urticarias. In vitro experiments
      suggest that mast cells respond directly to these stimuli, implying that a
      signaling mechanism couples functional responses to physical inputs in mast
      cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation
      channels were present and functionally coupled to signaling pathways in mast
      cells, since expression of this channel subfamily confers sensitivity to thermal,
      osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in
      mast cells, and we report the expression, surface localization, and
      oligomerization of TRPV2 protein subunits in these cells. We describe the
      functional coupling of TRPV2 protein to calcium fluxes and proinflammatory
      degranulation events in mast cells. In addition, we describe a novel protein
      kinase A (PKA)-dependent signaling module, containing PKA and a putative A kinase
      adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with
      TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a
      common pathway for TRPV modulation.

PMID- 15249592
TI  - Role of natural killer cells in innate protection against lethal ebola virus
      infection.
AB  - Ebola virus is a highly lethal human pathogen and is rapidly driving many wild
      primate populations toward extinction. Several lines of evidence suggest that
      innate, nonspecific host factors are potentially critical for survival after
      Ebola virus infection. Here, we show that nonreplicating Ebola virus-like
      particles (VLPs), containing the glycoprotein (GP) and matrix protein virus
      protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced
      protective immunity. VLP injection enhanced the numbers of natural killer (NK)
      cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK
      cells enhanced cytokine secretion and cytolytic activity against NK-sensitive
      targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with
      VLPs had no protective effect against Ebola virus infection and NK cells treated
      with VLPs protected against Ebola virus infection when adoptively transferred to
      naive mice. The mechanism of NK cell-mediated protection clearly depended on
      perforin, but not interferon-gamma secretion. Particles containing only VP40 were
      sufficient to induce NK cell responses and provide protection from infection in
      the absence of the viral GP. These findings revealed a decisive role for NK cells
      during lethal Ebola virus infection. This work should open new doors for better
      understanding of Ebola virus pathogenesis and direct the development of
      immunotherapeutics, which target the innate immune system, for treatment of Ebola
      virus infection.

PMID- 15249593
TI  - GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T
      cells in graft-versus-host disease.
AB  - Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR)
      is a member of the tumor necrosis factor receptor (TNFR) family that is expressed
      at low levels on unstimulated T cells, B cells, and macrophages. Upon activation,
      CD4(+) and CD8(+) T cells up-regulate GITR expression, whereas immunoregulatory T
      cells constitutively express high levels of GITR. Here, we show that GITR may
      regulate alloreactive responses during graft-versus-host disease (GVHD) after
      allogeneic bone marrow transplantation (BMT). Using a BMT model with major
      histocompatibility complex class I and class II disparity, we demonstrate that
      GITR stimulation in vitro and in vivo enhances alloreactive CD8(+)CD25(-) T cell
      proliferation, whereas it decreases alloreactive CD4(+)CD25(-) proliferation.
      Allo-stimulated CD4(+)CD25(-) cells show increased apoptosis upon GITR
      stimulation that is dependent on the Fas-FasL pathway. Recipients of an allograft
      containing CD8(+)CD25(-) donor T cells had increased GVHD morbidity and mortality
      in the presence of GITR-activating antibody (Ab). Conversely, recipients of an
      allograft with CD4(+)CD25(-) T cells showed a significant decrease in GVHD when
      treated with a GITR-activating Ab. Our findings indicate that GITR has opposite
      effects on the regulation of alloreactive CD4(+) and CD8(+) T cells.

PMID- 15249594
TI  - Enhanced TCR-induced apoptosis in interferon regulatory factor 4-deficient CD4(+)
      Th cells.
AB  - Transcription factors of the interferon regulatory factor (IRF) family contribute
      to the regulation of cell proliferation and apoptosis. Here, we show that CD4(+)
      T helper (Th) cells lacking IRF4 (IRF4(-/-)) are highly sensitive to apoptosis.
      After infection of IRF4(-/-) mice with the protozoan parasite Leishmania major,
      the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild
      type mice after 4 wk, but demonstrated almost total loss of cellularity and
      enhanced apoptosis after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells
      led to greatly increased apoptosis compared with wild-type cells. Coculture of
      IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4(-/-)
      CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th cell apoptosis
      was neither transferable nor due to lack of a cytokine. Enhanced CD4(+) cell
      apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95
      expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to
      increased and equally high levels of IRF4(-/-) and IRF4(+/+) cell apoptosis,
      whereas the protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+)
      cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central
      in protecting CD4(+) cells against proapoptotic stimuli.

PMID- 15249595
TI  - Rapid turnover of effector-memory CD4(+) T cells in healthy humans.
AB  - Memory T cells can be divided into central-memory (T(CM)) and effector-memory
      (T(EM)) cells, which differ in their functional properties. Although both
      subpopulations can persist long term, it is not known whether they are maintained
      by similar mechanisms. We used in vivo labeling with deuterated glucose to
      measure the turnover of CD4(+) T cells in healthy humans. The CD45R0(+)CCR7(-)
      T(EM) subpopulation was shown to have a rapid proliferation rate of 4.7% per day
      compared with 1.5% per day for CD45R0(+)CCR7(+) T(CM) cells; these values are
      equivalent to average intermitotic (doubling) times of 15 and 48 d, respectively.
      In contrast, the CD45RA(+)CCR7(+) naive CD4(+) T cell population was found to be
      much longer lived, being labeled at a rate of only 0.2% per day (corresponding to
      an intermitotic time of approximately 1 yr). These data indicate that human
      CD4(+) T(EM) cells constitute a short-lived cell population that requires
      continuous replenishment in vivo.

PMID- 15249597
TI  - Measuring specific interaction of transcription factor ZmDREB1A with its DNA
      responsive element at the molecular level.
AB  - Specific interactions between transcription factors and DNA responsive elements
      are of fundamental importance in understanding how genetic regulatory proteins
      control gene transcription. Here we have developed a new method of using atomic
      force microscopy (AFM) to quantitatively study the single molecular specific
      interaction between ZmDREB1A, a transcription factor from maize, and its DNA
      responsive element, dehydration-responsive element (DRE) with core sequence
      A/GCCGAC. It was found that ZmDREB1A bound to both DRE ACCGAC and GCCGAC
      efficiently. The single molecular interaction forces of ZmDREB1A with DRE
      A/GCCGAC were determined to be 101 +/- 5 and 108 +/- 3 pN, respectively. The
      point mutation of ZmDREB1A in its DNA-binding domain or single base substitution
      of the DRE core sequence greatly reduced the binding affinity, demonstrating the
      high sensitivity of the AFM measurements. AFM is expected to be a simple, quick,
      sensitive and reliable method that offers valuable information for the
      characterization of transcription factors and the identification of their
      potential DNA responsive elements in functional genomics research.

PMID- 15249596
TI  - Measurement of DNA mismatch repair activity in live cells.
AB  - Loss of DNA mismatch repair (MMR) function leads to the development and
      progression of certain cancers. Currently, assays for DNA MMR activity involve
      the use of cell extracts and are technically challenging and costly. Here, we
      report a rapid, less labor-intensive method that can quantitatively measure MMR
      activity in live cells. A G-G or T-G mismatch was introduced into the ATG start
      codon of the enhanced green fluorescent protein (EGFP) gene. Repair of the G-G or
      T-G mismatch to G-C or T-A, respectively, in the heteroduplex plasmid generates a
      functional EGFP gene expression. The heteroduplex plasmid and a similarly
      constructed homoduplex plasmid were transfected in parallel into the same cell
      line and the number of green cells counted by flow cytometry. Relative EGFP
      expression was calculated as the total fluorescence intensity of cells
      transfected with the heteroduplex construct divided by that of cells transfected
      with the homoduplex construct. We have tested several cell lines from both MMR
      deficient and MMR-proficient groups using this method, including a colon
      carcinoma cell line HCT116 with defective hMLH1 gene and a derivative
      complemented by transient transfection with hMLH1 cDNA. Results show that MMR
      proficient cells have significantly higher EGFP expression than MMR-deficient
      cells, and that transient expression of hMLH1 alone can elevate MMR activity in
      HCT116 cells. This method is potentially useful in comparing and monitoring MMR
      activity in live cells under various growth conditions.

PMID- 15249598
TI  - A universal transgene silencing method based on RNA interference.
AB  - Inducible gene expression systems have contributed significantly to the
      understanding of molecular regulatory networks. Here we describe a simple and
      powerful RNA interference-based method that can silence the expression of any
      transgene. We first used an IRES bicistronic lentiviral vector and showed that
      targeting the second cistron with a specific siRNA resulted in silencing of both
      transgenes. We then inserted a siRNA minimal target sequence in the 3'
      untranslated region (3'-UTR) of a transgene and showed that the cognate siRNA
      delivered by a lentiviral vector led to the partial silencing of the transgene.
      The multimerization of this siRNA target sequence led to the highly efficient
      silencing of four different transgenes. This new method to silence transgene
      expression is more versatile than existing methods of conditional inactivation of
      gene expression, such as transcriptional switches or site-specific recombination.
      It is applicable to a wide variety of models including primary cells, terminally
      differentiated cells and transgenic animals.

PMID- 15249601
TI  - Hypertension and the brain: stroke is just the tip of the iceberg.

PMID- 15249599
TI  - Investigations on DNA intercalation and surface binding by SYBR Green I, its
      structure determination and methodological implications.
AB  - The detection of double-stranded (ds) DNA by SYBR Green I (SG) is important in
      many molecular biology methods including gel electrophoresis, dsDNA
      quantification in solution and real-time PCR. Biophysical studies at defined
      dye/base pair ratios (dbprs) were used to determine the structure-property
      relationships that affect methods applying SG. These studies revealed the
      occurrence of intercalation, followed by surface binding at dbprs above
      approximately 0.15. Only the latter led to a significant increase in
      fluorescence. Studies with poly(dA)* poly(dT) and poly(dG)* poly(dC) homopolymers
      showed sequence-specific binding of SG. Also, salts had a marked impact on SG
      fluorescence. We also noted binding of SG to single-stranded (ss) DNA, although
      SG/ssDNA fluorescence was at least approximately 11-fold lower than with dsDNA.
      To perform these studies, we determined the structure of SG by mass spectrometry
      and NMR analysis to be [2-[N-(3-dimethylaminopropyl)-N-propylamino]-4-[2,3
      dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene]-1-phenyl-quinolinium]. For
      comparison, the structure of PicoGreen (PG) was also determined and is [2-[N-bis
      (3-dimethylaminopropyl)-amino]-4-[2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)
      methylidene]-1-phenyl-quinolinium]+. These structure-property relationships help
      in the design of methods that use SG, in particular dsDNA quantification in
      solution and real-time PCR.

PMID- 15249602
TI  - "Do try this at home": self-treatment of BPPV.

PMID- 15249603
TI  - Ictal SPECT analysis in epilepsy: subtraction and statistical parametric mapping
      techniques.
AB  - Seizures are associated with an increase in regional cerebral blood flow (rCBF).
      In partial seizures the increased blood flow closely corresponds with the site of
      seizure origin. Using tracers that accumulate and remain "fixed" in different
      areas of the brain proportional to rCBF at the time of injection, ictal SPECT is
      now an important tool for localization of seizures in a presurgical evaluation.
      However, the best methods for interpretation of partial seizure-induced changes
      in rCBF remain unclear. Numerous computer-aided tools have been used to increase
      objectivity and accuracy of ictal SPECT analysis. This review examines the uses
      of ictal-interictal subtraction methods and statistical parametric mapping (SPM)
      to enhance interpretation and utility of ictal SPECT. The review covers the
      evolution of advanced ictal SPECT imaging analysis techniques and the authors'
      clinical experience with the use of subtraction and SPM methods. The authors
      discuss the impact of ictal SPECT subtraction or difference imaging methods and
      the initial evidence for proof-of-principle that SPM can be used to provide
      objective, accurate analysis of ictal SPECT scans in patients with temporal and
      extratemporal lobe epilepsy. The limitations of both methodologies are discussed,
      and suggestions for further study of validation, improvement, and routine
      clinical implementation of advanced analysis methods are provided.

PMID- 15249604
TI  - Left ventricular hypertrophy is associated with cerebral microbleeds in
      hypertensive patients.
AB  - BACKGROUND: Cerebral microbleeds (CMBs) are indicative of hemorrhage-prone
      microangiopathy and known to be closely associated with chronic hypertension.
      However, no studies have been undertaken on the association between left
      ventricular (LV) hypertrophy and the severity of CMB. METHODS: One hundred two
      consecutive stroke patients with hypertension were examined. CMBs were counted
      using T2*-weighted gradient echo MRI data. With use of ordinal logistic
      regression analysis, the associations between LV mass index and other vascular
      risk factors and CMBs were analyzed. RESULTS: Hypertensive patients with CMBs
      showed a higher LV mass index than patients without. The grades of LV mass index
      were significantly correlated with the grades of CMB in the whole brain (p =
      0.02), in the central gray matter (p < 0.01), and in the infratentorial area (p <
      0.01), but not with those in the subcortical white matter. Ordinal regression
      analysis revealed that the LV mass index was independently associated with
      increased CMB severity (p = 0.01), regionally in the central gray matter (p <
      0.01) and in the infratentorial area (p < 0.01), but not in the subcortical white
      matter (p = 0.63). After excluding patients with cerebral amyloid angiopathy, the
      association between the LV mass index and the CMB severity in the subcortical
      white matter became significant (p < 0.01). CONCLUSIONS: There is a close
      relationship between CMBs and LV hypertrophy in hypertensive patients with
      stroke. Thus, CMBs should be understood as one type of cerebral target organ
      damage by chronic hypertension.

PMID- 15249605
TI  - Does acute occlusion of the carotid T invariably have a poor outcome?
AB  - OBJECTIVE: To evaluate the prognosis of patients with acute occlusion of the
      carotid T. METHODS: The authors studied 42 consecutive patients with acute
      carotid T occlusion, age 66 (59 to 74) years (median [interquartile range]). T
      occlusion was diagnosed with transcranial Doppler sonography (TCD; n = 11) and MR
      (n = 28) or CT (n = 3) angiography. Final infarction size was evaluated on follow
      up CT 3 to 7 days after symptom onset and recanalization by follow-up TCD 24 to
      36 hours after symptom onset. RESULTS: NIH Stroke Scale (NIHSS) score on
      admission was 18 (16 to 20). Final infarct size was one-third or less of the
      middle cerebral artery (MCA) territory in 11, greater than one-third but less
      than or equal to two-thirds of the MCA territory in 10, and greater than two
      thirds of the MCA territory in 21 patients. Modified Rankin Scale (mRS) score 6
      months after stroke onset was 2 in 7 (17%), 3 in 2 (5%), 4 in 13 (31%), 5 in 7
      (17%), and 6 in 13 (31%) patients. Complete or partial MCA recanalization within
      24 hours after symptom onset was observed in 12 of 18 patients treated with
      thrombolysis and 4 of the remaining 24 patients (p = 0.001) and was associated
      with better clinical outcome (mRS 2, recanalization 6/7 [86%]; mRS 3 to 5,
      recanalization 8/22 [36%]; mRS 6, recanalization 2/13 [15%]; p = 0.01).
      Recanalization and NIHSS score on admission were independent predictors of
      outcome. CONCLUSIONS: Acute carotid T occlusion does not necessarily carry a poor
      prognosis. IV thrombolysis frequently results in recanalization, which is related
      to a better clinical outcome and smaller final infarction size.

PMID- 15249606
TI  - High lipoprotein (a), diabetes, and the extent of symptomatic intracranial
      atherosclerosis.
AB  - BACKGROUND: Lipoprotein (a) (Lp[a]) has important atherothrombogenic properties,
      but its role in intracranial atherosclerosis remains unclear. OBJECTIVE: To
      investigate the relationship between Lp(a) level and the extent of intracranial
      large-artery occlusive disease. METHODS: Between June 2001 and August 2003, 166
      consecutive first-ever TIA or stroke patients had intracranial stenoses on
      transcranial Doppler, of which 100 fulfilled all inclusion criteria. The extent
      of intracranial large-artery occlusive disease was assessed by the number of
      angiographically confirmed intracranial stenoses. Serum Lp(a) was determined a
      minimum of 3 months after stroke onset. RESULTS: Two hundred eighty-one
      intracranial stenoses were documented. Fifty-one (51%) patients had three or more
      stenoses (greater-extent group). Patients in the highest Lp(a) quartile had a
      higher adjusted odds ratio (OR) for a greater extent than those in the lowest
      quartile (OR 3.43, 95% CI 1.04 to 11.33, p = 0.04). A positive correlation was
      found between Lp(a) concentration and the number of stenoses (r = 0.310, p =
      0.002). Moreover, Lp(a) level increased gradually with the number of stenoses (p
      = 0.02). A multiple logistic regression model identified diabetes (OR 2.4, 95% CI
      1.04 to 5.57, p = 0.04) and high Lp(a) (OR 2.52, 95% CI 1.03 to 6.18, p = 0.043)
      as independent markers of a greater extent of intracranial large-artery occlusive
      disease. CONCLUSIONS: High Lp(a) level and diabetes mellitus are independent
      markers of a greater extent of intracranial large-artery occlusive disease. These
      findings support a role for Lp(a) in intracranial stenotic atherogenesis and
      might be useful for the selection of high-risk patients.

PMID- 15249607
TI  - Copper deficiency myelopathy produces a clinical picture like subacute combined
      degeneration.
AB  - BACKGROUND: Copper deficiency in ruminants is known to cause an ataxic
      myelopathy. Copper deficiency as a cause of progressive myelopathy in adults is
      underrecognized. OBJECTIVE: To describe the clinical, biochemical,
      electrophysiologic, and imaging characteristics in 13 patients with myelopathy
      associated with copper deficiency. METHODS: The records of patients with a copper
      deficiency-associated myelopathy were reviewed. Clinical characteristics,
      laboratory investigations, and responses to therapeutic intervention were
      summarized. RESULTS: Thirteen such patients were found, 11 of them in a 15-month
      period. All patients presented with prominent gait difficulty, reflecting a
      sensory ataxia due to dorsal column dysfunction and lower limb spasticity. All
      patients had polyneuropathy. A high or high-normal serum zinc level was seen in 7
      of the 11 patients for whom this information was available. Somatosensory evoked
      potential studies done in eight patients showed impaired conduction in central
      proprioceptive pathways. Dorsal column signal change on spine MRI was present in
      three patients. An initial clue to the diagnosis was a very low ceruloplasmin
      level; further tests of copper metabolism excluded Wilson disease. The cause
      remained unexplained in most patients. Oral copper supplementation restored
      normal or near-normal copper levels in 7 of the 12 patients in whom adequate
      follow-up data were available; parenteral supplementation restored normal level
      in 3 further patients. Copper supplementation prevented further neurologic
      deterioration, but the degree of actual improvement was variable. CONCLUSIONS:
      Unrecognized copper deficiency appears to be a common cause of idiopathic
      myelopathy in adults. The clinical picture bears striking similarities to the
      syndrome of subacute combined degeneration associated with vitamin B12
      deficiency. Early recognition and copper supplementation may prevent neurologic
      deterioration.

PMID- 15249608
TI  - Paroxysmal eyelid movements: a confusing feature of generalized photosensitive
      epilepsy.
AB  - BACKGROUND: Persistent, frequent, nonepileptic paroxysmal eyelid movements were
      observed in 19 children and adults with well-controlled generalized epilepsy.
      METHODS: Patients were identified from five epilepsy centers. RESULTS: Seventeen
      patients were female and two male. All had generalized photosensitive epilepsy
      requiring antiepileptic drugs (AEDs). In two children, paroxysmal eyelid
      movements began 2 to 4 years before their epilepsy was noted; in the remainder,
      it was noted when epilepsy was first diagnosed. Age at last follow-up was 8 to 38
      years (average 21 years) with average follow-up of 9 years. All patients showed
      photosensitive generalized spike-wave discharges on EEG. Paroxysmal eyelid
      movements were a source of diagnostic confusion, but direct examination and video
      during EEG recording distinguished the attacks from absence seizures. In all
      cases, the epilepsy is completely or nearly completely controlled with AEDs, but
      the paroxysmal eyelid movements have not resolved with age. In 12 cases, there
      was a family history of the eyelid disorder without epilepsy. Videos of patients
      and an affected parent are available on the Neurology Web site. CONCLUSION: There
      is an association between paroxysmal eyelid movements and photosensitive
      generalized epilepsy, creating diagnostic confusion.

PMID- 15249609
TI  - Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen
      encephalitis.
AB  - OBJECTIVE: To determine the prevalence of serum antibodies to the ionotropic
      glutamate receptor 3 (GluR3) in patients with Rasmussen encephalitis (RE), a
      severe epileptic disorder, and to compare with serum from control subjects and
      patients with intractable epilepsy (IE). METHODS: The authors looked for serum
      immunoglobulin (Ig) G antibodies to GluR3 in 30 patients with RE, including two
      patients who had plasma exchange and 12 who had been treated with IV Igs with
      varying results, and 49 patients with IE and 23 healthy individuals, using ELISA
      with GluR3B peptide, Western blot analysis of recombinant full-length GluR3,
      immunoprecipitation of [35S]- and [125I]-labeled GluR3 extracellular domains,
      immunohistochemistry on rat brain sections, and electrophysiology of GluR3
      expressed in Xenopus oocytes. RESULTS: Low levels of antibodies to the GluR3B
      peptide were detected using ELISA in only 4 of the 79 patients with epilepsy (2
      with RE and 2 with IE); binding to GluR3B in other sera was shown to be
      nonspecific. One other patient with IE had antibodies to recombinant GluR3 on
      Western blot analysis. However, none of the sera tested precipitated either the
      [35S]- or the [125I]-labeled GluR3 domains; none bound to rat brain sections in a
      manner similar to rabbit antibodies to GluR3; and none of the nine sera tested
      affected the electrophysiologic function of GluR3. CONCLUSIONS: GluR3 antibodies
      were only infrequently found in Rasmussen encephalitis or intractable epilepsy.

PMID- 15249610
TI  - Germline and mosaic mutations of FLN1 in men with periventricular heterotopia.
AB  - OBJECTIVE: To describe the phenotypic spectrum and genetics of periventricular
      nodular heterotopia (PNH) caused by FLN1 mutations in four men. BACKGROUND: X
      linked PNH caused by FLN1 mutations (MIM #300049) implies prenatal or early
      postnatal lethality in boys and 50% recurrence risk in daughters of affected
      women. METHODS: Clinical examination, cognitive testing, MRI, and mutation
      analysis (denaturing high-performance liquid chromatography and direct
      sequencing) on blood lymphocytes and single hair roots were performed for nine
      affected individuals, including three men. Neuropathologic study of the brain was
      performed for an affected boy. RESULTS: In two families, missense mutations were
      transmitted from mother to son (Met102Val) and from father to daughter
      (Ser149Phe), causing mild phenotypes in both genders, including unilateral PNH.
      In a third family, a man was mosaic for an A>G substitution (intron 11 acceptor
      splice site) on leukocyte DNA and hair roots (mutant = 42% and 69%). Single hair
      root analysis confirmed that the mutation was not present in all ectodermal
      derivative cells. A healthy daughter had inherited the X chromosome from her
      father's wild-type germinal cell population. In the fourth family, an eight-base
      deletion (AGGAGGTG, intron 25 donor splice site) led to early deaths of boys.
      Postmortem study in a newborn boy revealed PNH and cardiovascular, genitourinary,
      and gut malformations. CONCLUSIONS: Periventricular nodular heterotopia caused by
      FLN1 mutations in men has a wide clinical spectrum and is caused by different
      genetic mechanisms, including somatic mosaicism. Mutation analysis of FLN1 should
      support genetic counseling in men with periventricular nodular heterotopia.

PMID- 15249611
TI  - A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and
      mental retardation.
AB  - BACKGROUND: Benign familial neonatal convulsion (BFNC) is a rare autosomal
      dominant disorder caused by mutations in two genes, KCNQ2 and KCNQ3, encoding for
      potassium channel subunits underlying the M-current. This current limits neuronal
      hyperexcitability by causing spike-frequency adaptation. METHODS: The authors
      describe a BFNC family with four affected members: two of them exhibit BFNC only
      while the other two, in addition to BFNC, present either with a severe epileptic
      encephalopathy or with focal seizures and mental retardation. RESULTS: All
      affected members of this family carry a novel missense mutation in the KCNQ2 gene
      (K526N), disrupting the tri-dimensional conformation of a C-terminal region of
      the channel subunit involved in accessory protein binding. When heterologously
      expressed in CHO cells, potassium channels containing mutant subunits in
      homomeric or heteromeric configuration with wild-type KCNQ2 and KCNQ3 subunits
      exhibit an altered voltage-dependence of activation, without changes in
      intracellular trafficking and plasma membrane expression. CONCLUSION: The KCNQ2
      K526N mutation may affect M-channel function by disrupting the complex
      biochemical signaling involving KCNQ2 C-terminus. Genetic rather than acquired
      factors may be involved in the pathophysiology of the phenotypic variability of
      the neurologic symptoms associated with BFNC in the described family.

PMID- 15249612
TI  - Onset and rate of striatal atrophy in preclinical Huntington disease.
AB  - BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that
      begins long before the onset of motor symptoms. OBJECTIVE: To determine when
      striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor
      symptoms, and whether striatal atrophy can predict when symptom onset will occur.
      METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical
      subjects with the HD gene expansion who were very far (9 to 20 years) from
      estimated onset, and on serial scans from 17 preclinical subjects, six of whom
      were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal
      volumes were significantly smaller for the subjects who were very far from
      estimated onset than for age-matched control subjects. Statistical models fit to
      the longitudinal data suggest that rate of caudate atrophy becomes significant
      when subjects are approximately 11 years from estimated onset and rate of putamen
      atrophy becomes significant approximately 9 years prior to onset. In the six
      incident cases, caudate and putamen were approximately one-third to one-half of
      normal volume at diagnosis, and caudate volume alone was able to predict with
      100% accuracy those subjects who would be diagnosed within 2 years of imaging.
      CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and
      assessment of atrophy on MRI may be very useful in both predicting HD onset and
      in tracking progression in future therapeutic trials in preclinical subjects.

PMID- 15249613
TI  - PET evidence for a role of the basal ganglia in patients with ring chromosome 20
      epilepsy.
AB  - BACKGROUND: Studies in animal models and epileptic patients have suggested that
      circuits of the basal ganglia may control epileptic seizures and that striatal
      dopaminergic transmission plays a key role in seizure interruption. Ring
      chromosome 20 (r[20]) epilepsy is a very homogenous type of epilepsy and is
      clinically characterized by long-lasting seizures suggesting a dysfunction in the
      seizure control system. The hypothesis that these long-lasting seizures are
      associated with a reduction of striatal dopamine was addressed in the present
      study in drug-resistant patients with r(20) epilepsy using PET. METHOD: The
      authors performed [18F]fluoro-l-DOPA PET in 14 patients with r(20) epilepsy and
      compared uptake constants in the putamen and the caudate with those of 10
      controls. In addition, the authors examined the correlation between these
      constants and the percentage of cells with r(20) mosaicism. RESULTS: [18F]fluoro
      l-DOPA uptake was significantly decreased bilaterally in the putamen and in the
      caudate nucleus of patients. This reduction was equal for both nuclei and was not
      correlated to the percentage of cells with r(20). CONCLUSION: Striatal dopamine
      is modulated in r(20) epilepsy; dysfunction of this neurotransmission may impair
      the mechanisms that interrupt seizures.

PMID- 15249614
TI  - Disorganized search on cancellation is not a consequence of neglect.
AB  - BACKGROUND: Some studies have suggested that in stroke patients, spatial
      inattention on the cancellation test is closely related to disorganized visual
      search. However, methods to assess spatial aspects of search organization on
      cancellation tests have not been well developed. In this study the authors design
      and evaluate new methods to quantify strategies of spatial exploration on the
      cancellation test in stroke patients who showed a broad range of spatial
      attentional abilities, and test whether disorganization and inattention are
      related. METHODS: Twenty stroke patients were videotaped while they performed a
      cancellation test. Several variables that reflect spatial aspects of search
      organization were measured through subsequent video playback. Two patients with
      severe neglect were excluded from further analysis to avoid constraining the
      spatial expression of search organization. Spearman correlations were used to
      assess whether severity of spatial inattention correlated with the individual
      search organization measures. RESULTS: Of the 18 remaining patients, 10 had mild
      moderate spatial neglect (pathologic inattention), while the other 8 omitted at
      most one target (normal performance). There were no significant correlations
      between the number of targets omitted and any of the search organization
      measures. CONCLUSIONS: Spatial inattention on cancellation due to neglect
      following stroke is not closely related to the organization of visual search.
      Instead, search disorganization during cancellation may reflect disturbance of an
      unspecified executive control mechanism.

PMID- 15249615
TI  - Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected
      individuals.
AB  - OBJECTIVE: To identify alternatives to the CSF-Venereal Disease Research
      Laboratory (VDRL) test for the diagnosis of neurosyphilis in HIV-infected
      individuals. METHODS: CSF fluorescent treponemal antibody (FTA) reactivity and %
      CSF lymphocytes that were B cells in fresh and frozen samples were determined for
      47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum,
      CSF fluorescent treponemal antibody reactivity > or =2+ was considered positive.
      Based on the results in controls and cases with normal CSF measures, cut-offs for
      elevated CSF B cells were proposed to be > or =9% in fresh and > or =20% in
      frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL. RESULTS: CSF
      FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for
      the diagnosis of neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved
      samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses.
      The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of
      cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with
      neurosyphilis and 26% to be diagnosed as not having neurosyphilis. CONCLUSION:
      When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or
      establish the diagnosis of neurosyphilis.

PMID- 15249616
TI  - Neocortical volume decrease in relapsing-remitting MS patients with mild
      cognitive impairment.
AB  - OBJECTIVE: To assess neocortical changes and their relevance to cognitive
      impairment in early relapsing-remitting (RR) multiple sclerosis (MS). METHODS:
      Conventional MR was acquired in 41 patients with RR MS and 16 demographically
      matched normal control subjects (NCs). An automated analysis tool was used with
      conventional T1-weighted MRI to obtain measures of cortical brain volumes
      normalized for head size. Neuropsychological performance of MS patients was
      assessed using the Rao Brief Repeatable Battery. Relationship between volumetric
      MR measures and neuropsychological scores was assessed. RESULTS:
      Neuropsychological assessment allowed for the identification of 18 cognitively
      preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS
      sample showed lower values of normalized cortical volumes (NCVs) than did the NC
      group (p = 0.01). Upon grouping of MS patients according to cognitive
      performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS
      cp patients and NCs. Moreover, there were positive correlations between NCV
      values and measures of verbal memory (r = 0.51, p = 0.02), verbal fluency (r =
      0.51, p = 0.01), and attention/concentration (r = 0.65, p < 0.001) in MS-ci
      patients. Furthermore, NCV values were decreased in patients who scored lower on
      a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the
      neuropsychological measures correlated to NCV values in the MS-cp patient group.
      CONCLUSIONS: Cortical atrophy was found only in cognitively impaired patients and
      was significantly correlated with a poorer performance on tests of verbal memory,
      attention/concentration, and verbal fluency. Gray matter pathology may contribute
      to the development of cognitive impairment in MS from the earliest stages of the
      disease.

PMID- 15249617
TI  - Medial temporal lobe atrophy on MRI predicts dementia in patients with mild
      cognitive impairment.
AB  - BACKGROUND: Although detailed volumetric MRI assessment of medial temporal lobe
      atrophy (MTA) can predict dementia in patients with mild cognitive impairment
      (MCI), it is not easily applied to routine clinical practice. OBJECTIVE: To test
      the predictive accuracy of visually assessed MTA in MCI patients using a
      standardized visual rating scale. METHODS: Seventy-five MCI patients (mean age 63
      years) underwent a coronal three-dimensional magnetization-prepared rapid
      gradient echo brain MRI sequence. MTA was rated visually using a 5-point rating
      scale. RESULTS: The mean follow-up period for the cohort was 34 months. At follow
      up, 49% of the enrolled MCI patients fulfilled criteria for dementia. MTA
      assessed using a standardized visual rating scale was significantly associated
      with dementia at follow-up, with a hazard ratio of 1.5 for every point increase
      in atrophy score (p < 0.001) and of 3.1 for the presence of atrophy based on the
      dichotomized atrophy score (p = 0.003). The predictive accuracy of visually
      assessed MTA was independent of age, gender, education, Mini-Mental State
      Examination score, Clinical Dementia Rating Sum of Boxes score, Verbal Delayed
      Recall, and the presence of hypertension, depression, the APOE epsilon4 allele,
      and white matter hyperintensities. CONCLUSIONS: Visual assessment of MTA on brain
      MRI using a standardized rating scale is a powerful and independent predictor of
      conversion to dementia in relatively young MCI patients. As overlap existed in
      MTA scores between patients with and without dementia at follow-up, the results
      should be interpreted in the light of the odds for the individual patient.

PMID- 15249618
TI  - Postmenopausal hormone therapy and risk of cognitive decline in community
      dwelling aging women.
AB  - BACKGROUND: A randomized trial of postmenopausal women over age 65 reported
      increased risks of cognitive decline with 4 years of combined estrogen and
      progestin treatment. However, questions remain, including the effect of longer
      duration or of hormone therapy initiated at younger ages. METHODS: The Nurses'
      Health Study is a prospective cohort begun in 1976, comprising 121,700 female
      nurses who report health information via biennial mailed questionnaires. This
      substudy includes 13,807 participants age 70 to 81 who completed two telephone
      cognitive assessments, 2 years apart, between 1995 and 2003. General cognition,
      verbal memory, category fluency, and attention were tested. Multiple linear
      regression was used to estimate adjusted mean declines and logistic regression to
      estimate adjusted risks of substantial decline in cognition (> or =2 SD of
      baseline performance) across hormone groups. APOE genotype was available in a
      subset of 3,667 participants. RESULTS: Overall, little difference was found in
      mean cognitive decline between current hormone users and never users. However,
      for long-term users of estrogen alone or combined with progestin, increased risk
      of substantial decline was observed on most cognitive tests (relative risk [RR] =
      1.25 to 1.72). Decline was particularly high among women initiating hormones at
      older ages compared with never users: for example, on our test of general
      cognition, RR of substantial decline was 1.74 (95% CI 1.08, 2.81) and mean
      difference in decline was -0.43 (95% CI -0.73, -0.12). No significant
      interactions between hormone use and APOE epsilon4 allele were observed.
      CONCLUSION: Postmenopausal hormone therapy provides no appreciable cognitive
      benefits in older women.

PMID- 15249619
TI  - Predicting the rate of cognitive decline in aging and early Alzheimer disease.
AB  - OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer
      disease (AD) and to determine the role of region-specific brain volumes as
      predictors of cognitive decline. METHODS: Longitudinal data from 166 normal
      elderly individuals and 59 early AD patients were analyzed. Brain volumes were
      extracted from MRI scans using semiautomated recursive segmentation methods.
      Prognostic factors were considered significant if they had a significant effect
      on the rate of cognitive decline. RESULTS: In multivariate analysis, higher
      Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic
      factor for an increased rate of cognitive decline. Significant prognostic factors
      within the baseline CDR = 0 group were base rate of progression and percent total
      high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base
      rate of progression, family history, and percent ventricular volume were
      significant prognostic factors within the CDR = 0.5 group and APOE had a
      marginally significant effect on the rate of cognitive decline in the CDR = 1
      group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures
      can independently predict the rate of cognitive decline and improve the
      predictive power of statistical models that use only clinical data. Brain
      volumetric measures from MRI can be used to estimate the rate of cognitive
      decline even among normal elderly individuals and thus may aid in the prediction
      of time of onset of disease.

PMID- 15249620
TI  - Mild cognitive impairment, amnestic type: an epidemiologic study.
AB  - OBJECTIVE: To estimate the prevalence and examine the course of mild cognitive
      impairment (MCI), amnestic type, using current criteria, within a representative
      community sample. METHODS: Retroactive application of MCI criteria to data
      collected during a prospective epidemiologic study was performed. The subjects
      were drawn from voter registration lists, composing a cohort of 1,248 individuals
      with mean age of 74.6 (5.3) years, who were nondemented at entry and who were
      assessed biennially over 10 years of follow-up. The Petersen amnestic MCI
      criteria were operationalized as 1) impaired memory: Word List Delayed Recall
      score of <1 SD below mean; 2) normal mental status: Mini-Mental State Examination
      score of 25+; 3) normal daily functioning: no instrumental impairments; 4) memory
      complaint: subjective response to standardized question; 5) not demented:
      Clinical Dementia Rating Scale score of <1. RESULTS: At the five assessments,
      amnestic MCI criteria were met by 2.9 to 4.0% of the cohort. Of 40 persons with
      MCI at the first assessment, 11 (27%) developed dementia over the next 10 years.
      Over each 2-year interval, MCI persons showed increased risk of dementing (odds
      ratio = 3.9, 95% CI = 2.1 to 7.2); 11.1 to 16.7% progressed to Alzheimer disease
      and 0 to 5.0% progressed to other dementias. Over the same intervals, 11.1 to
      21.2% of those with MCI remained MCI; of 33.3 to 55.6% who no longer had MCI,
      half had reverted to normal. CONCLUSIONS: In this community-based sample, 3 to 4%
      of nondemented persons met MCI operational criteria; despite increased risk of
      progressing to dementia, a substantial proportion also remained stable or
      reverted to normal during follow-up. Amnestic MCI as currently defined is a high
      risk but unstable and heterogeneous group.

PMID- 15249621
TI  - Preserved visual-vestibular interaction in patients with bilateral vestibular
      failure.
AB  - BACKGROUND: During caloric vestibular stimulation, subjects showed bilateral
      activation of the vestibular cortex in the posterior insula and retroinsular
      region as well as concurrent deactivation of visual cortex areas bilaterally.
      This finding was the basis for the concept of a reciprocal inhibitory interaction
      between the vestibular and the visual systems. OBJECTIVE: To analyze the
      modulations of this activation and deactivation pattern in patients with loss of
      vestibular input, that is, in patients with bilateral vestibular failure (BVF).
      METHODS: Modulations of regional cerebral blood flow (rCBF) in PET were measured
      in nine patients with BVF and compared with those in healthy volunteers using
      statistical group as well as single-subject analyses (Statistical Parametric
      Mapping 96b). RESULTS: The group analysis of the BVF patients showed only one
      small region of activation in the posterior insula contralateral to the
      stimulated ear, whereas the other areas correlating with vestibular, autonomic,
      and ocular motor function were not activated. Furthermore, the concurrent rCBF
      decreases of the primary visual cortex seen in healthy volunteers were not found
      in the patients. These decreases seem to be dependent on an intact vestibular
      input with concurrent vestibular nystagmus. CONCLUSIONS: The results are
      compatible with the concept of a reciprocal inhibitory sensorisensory interaction
      between the vestibular and visual systems that normally act together for
      orientation in space and perception of motion. This interaction appears to be
      preserved in the patients at a significantly lower level, that is, with less
      activation and less deactivation.

PMID- 15249622
TI  - Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy.
AB  - BACKGROUND: Late-onset type I familial amyloid polyneuropathy (FAP TTR Met30)
      cases unrelated to endemic foci in Japan show clinical features setting them
      apart from early-onset cases in endemic foci. OBJECTIVE: To compare pathologic
      features between the early- and late-onset types. METHODS: Pathologic findings in
      FAP TTR Met30 with onset before age 50 in relation to endemic foci (11 cases)
      were compared with those in 11 later-onset cases unrelated to endemic foci.
      RESULTS: Sural nerve biopsy specimens showed predominantly small-fiber loss in
      early-onset cases; variable fiber size distribution, axonal sprouting, and
      relatively preserved unmyelinated fibers characterized late-onset cases. Autopsy
      cases representing both groups showed amyloid deposition throughout the length of
      nerves and in sympathetic and sensory ganglia, but amounts were greater in early
      onset cases. Amyloid deposition and neuronal cell loss were greater in
      sympathetic than dorsal root ganglia in early-onset cases; the opposite was true
      in late-onset cases. Size assessment of remaining neurons in these ganglia
      suggested predominant loss of small neurons in early-onset cases but loss of
      neurons of all sizes in late-onset cases. Transthyretin-positive, Congo red
      negative amorphous material was more conspicuous in nerves from late- than early
      onset cases. In extraneural sites, amyloid was more conspicuous in thyroid and
      kidney from early-onset cases and in heart and hypophysis from late-onset cases.
      In early-onset cases, cardiac amyloid deposition was prominent in the atrium and
      subendocardium but was conspicuous throughout the myocardium in late-onset cases.
      CONCLUSION: The pathology of early- and late-onset FAP TTR Met30 correlated well
      with differences in clinical findings.

PMID- 15249623
TI  - White matter lesion progression: a surrogate endpoint for trials in cerebral
      small-vessel disease.
AB  - There is neuropathologic evidence that confluent MRI white matter lesions in the
      elderly reflect ischemic brain damage due to microangiopathy. The authors
      hypothesize that measuring changes in the progression of white matter lesions as
      shown by MRI may provide a surrogate marker in clinical trials on cerebral small
      vessel disease in which the currently used primary outcomes are cognitive
      impairment and dementia. This hypothesis is based on evidence that confluent
      white matter lesions progress rapidly as shown in a recent follow-up study in
      community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3)
      after 3 years. Based on these data in a clinical trial, 195 subjects with
      confluent lesions would be required per treatment arm to demonstrate a 20%
      reduction in the rate of disease progression over a 3-year period. Like any other
      MRI metric, the change in white matter lesion volume cannot be considered
      preferable to clinical outcomes unless it has been demonstrated that it matters
      to the patient in terms of function.

PMID- 15249624
TI  - Midbrain vasculitic aneurysms.

PMID- 15249625
TI  - Detection of novel mutations in the SMN Tudor domain in type I SMA patients.
AB  - The authors present a complete SMN gene analysis in four type I unrelated spinal
      muscular atrophy patients who retained one copy of the SMN1 gene. Two intragenic
      point mutations were identified in exon 3 (I116F, Q136E), affecting a very
      conserved region with the Tudor domain of SMN1. The remaining two patients showed
      no alterations in the SMN1 coding sequences although a transcription defect was
      detected in one of them, corroborating the existence of non-functional SMN1
      genes.

PMID- 15249626
TI  - Self-treatment of benign paroxysmal positional vertigo: Semont maneuver vs Epley
      procedure.
AB  - The authors compared the efficacy of a self-applied modified Semont maneuver
      (MSM) with self-treatment with a modified Epley procedure (MEP) in 70 patients
      with posterior canal benign paroxysmal positional vertigo. The response rate
      after 1 week, defined as absence of positional vertigo and torsional/upbeating
      nystagmus on positional testing, was 95% in the MEP group (n = 37) vs 58% in the
      MSM group (n = 33; p < 0.001). Treatment failure was related to incorrect
      performance of the maneuver in the MSM group, whereas treatment-related side
      effects did not differ significantly between the groups.

PMID- 15249627
TI  - L-dopa-induced dyskinesia improvement after STN-DBS depends upon medication
      reduction.
AB  - The authors studied the long-term evolution of levodopa-induced dyskinesia (LID)
      after levodopa challenge in two groups of six STN-deep brain stimulation-treated
      Parkinson disease (PD) patients, one requiring medication after surgery and the
      other not. A dramatic (96%) reduction of LID severity was obtained in the six
      postoperatively untreated patients compared to a moderate improvement (47%) in
      the treated group (p < 0.03). These data support dopaminergic stimulation and
      striatal desensitization as major determinants of LID in PD.

PMID- 15249629
TI  - On-line anosognosia: unawareness for chorea in real time but not on videotape
      delay.
AB  - In hemiplegics, anosognosia (unawareness of deficit) rests on a mismatch between
      expected and actual movement: a feedback hypothesis emphasizes sensory deficits
      or neglect, a feedforward hypothesis postulates impaired intention to move.
      Anosognosia for other problems is less studied. The authors report a man without
      sensory deficits who was unaware of choreiform movements, except on videotape
      delay. The authors believe that a feed-forward mechanism underlies his "on-line"
      unawareness.

PMID- 15249628
TI  - Anti-basal ganglia antibodies in patients with atypical dystonia and tics: a
      prospective study.
AB  - Anti-basal ganglia antibodies (ABGA) are associated with movement disorders in
      children, but have not been assessed in adult onset movement disorders. In a
      prospective assessment ABGA were positive in 65% of a group of 65 patients with
      atypical movement disorders, but were very rare in healthy adults and adults with
      idiopathic dystonia. An autoimmune mechanism may underlie a proportion of cases
      of atypical movement disorders.

PMID- 15249630
TI  - Development and initial validation of a screening tool for Parkinson disease
      surgical candidates.
AB  - As there is currently no standardized assessment tool for evaluating Parkinson
      disease (PD) patients for deep brain stimulation (DBS), the authors developed the
      Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD). Part I of the
      study was a retrospective analysis of 174 patients presenting for a surgical
      screening. Part II was a multicenter study to assess the correlation of FLASQ-PD
      scores. The results of this study suggest that the FLASQ-PD may be a useful
      triage tool for screening PD patients for DBS surgery.

PMID- 15249631
TI  - Near-infrared spectrophotoscopy of finger venules in assessment of autonomic
      dysfunction.
AB  - The authors evaluated morphologic changes in the venules of the finger using near
      infrared spectrophotoscopy in patients with autonomic dysfunction, such as
      familial amyloidotic polyneuropathy and multiple-system atrophy. Abnormalities of
      the venules, such as tortuosity, irregular venous caliber, and microaneurysm-like
      change, and a linear negative correlation between the degree of orthostatic
      hypotension and the degree of vasoconstriction of the venules were observed.

PMID- 15249632
TI  - Clonal evolution as pathogenetic mechanism in relapse of primary CNS lymphoma.
AB  - Comparative investigation of immunoglobulin (Ig) heavy chain gene rearrangements
      and DNA sequence analyses of a primary lymphoma of the CNS (PCNSL) and its
      recurrence revealed that both tumors used the same Ig gene segment. In addition
      to shared somatic mutations, the primary and the recurrent PCNSLs harbored
      somatic mutations unique to each tumor. Clonal evolution rather than subclone
      selection appears to underlie the development of tumor recurrence in this case.

PMID- 15249633
TI  - Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing
      remitting MS.
AB  - The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal
      ganglia of patients with relapsing-remitting multiple sclerosis were investigated
      with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This
      technique facilitated the study of several bilateral structures in a single
      session at sub-cubic centimeter spatial resolution. Compared with 9 matched
      control subjects, the deep GM nuclei of 11 patients showed 7% lower N
      acetylaspartate and 14% higher choline levels (p = 0.02 for both).

PMID- 15249634
TI  - Possible association of nicastrin polymorphisms and Alzheimer disease in the
      Finnish population.
AB  - The authors previously reported that genetic variation in the gene coding for
      nicastrin (NCSTN) modified risk for familial early-onset Alzheimer disease (AD)
      in a Dutch population-based sample. Risk was highest in patients without an APOE
      epsilon4 allele. Here, they evaluated if NCSTN polymorphisms increased risk of AD
      in the eastern Finnish population. A significant difference in one haplotype was
      observed in AD patients without the APOE epsilon4 allele.

PMID- 15249635
TI  - Ventilatory support in facioscapulohumeral muscular dystrophy.
AB  - Respiratory insufficiency due to respiratory muscle weakness is a common
      complication of many neuromuscular diseases. The prevalence of respiratory
      failure in facioscapulohumeral muscular dystrophy (FSHD) is unknown. The authors
      identified 10 FSHD patients on nocturnal ventilatory support at home,
      representing approximately 1% of the Dutch FSHD population. Severe muscle
      disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors
      for respiratory failure.

PMID- 15249636
TI  - Improvement of a CIDP associated with hepatitis C virus infection using antiviral
      therapy.
AB  - A 57-year-old man with chronic inflammatory demyelinating polyneuropathy
      associated with hepatitis C virus infection was treated successfully with the
      combination of peginterferon-alpha-2b and ribavirin. Viral eradication was
      confirmed during the 4th week of treatment and was followed 3 weeks later by
      neurologic improvement. The patient resumed normal activity 1 year after the
      therapy was completed.

PMID- 15249637
TI  - Cerebral lipiodol embolism during transcatheter arterial chemoembolization.
AB  - Cerebral lipiodol embolism (CLE) is a rare complication that may occur during
      chemoembolization. The authors present three cases of CLE during transcatheter
      arterial chemoembolization for hepatocellular carcinoma. Multiple small
      nonconfluent hyperintense intracerebral lesions were found on the diffusion
      weighted and fluid-attenuated inversion recovery MRI. Clinical signs completely
      resolved and MRI lesions markedly improved on follow-up evaluation within a 3
      week period.

PMID- 15249638
TI  - Kluver-Bucy syndrome related to glioma.

PMID- 15249639
TI  - Thoracic syringomyelia and suspected multiple sclerosis: cause and effect or
      coincidence?

PMID- 15249640
TI  - CSF volume loss in spontaneous intracranial hypotension.

PMID- 15249641
TI  - Noninvasive imaging of carotid plaque inflammation.

PMID- 15249642
TI  - Tremor and deep white matter changes in alpha-methylacyl-CoA racemase deficiency.

PMID- 15249643
TI  - Vacuum cleaner epilepsy.

PMID- 15249644
TI  - Severe epilepsy, retardation, and dysmorphic features with a 2q deletion
      including SCN1A and SCN2A.

PMID- 15249645
TI  - Emotional prosody in primary progressive aphasia.

PMID- 15249646
TI  - Late onset Charcot-Marie-Tooth 2 syndrome caused by two novel mutations in the
      MPZ gene.

PMID- 15249647
TI  - Cesare Lombroso, cortical dysplasia, and epilepsy: keen findings and odd
      theories.

PMID- 15249648
TI  - A CAV3 microdeletion differentially affects skeletal muscle and myocardium.

PMID- 15249649
TI  - Involvement of the human subthalamic nucleus in movement preparation.

PMID- 15249650
TI  - Patient Page. Clinical research needs YOU to help develop new cures!

PMID- 15249651
TI  - Update for the neurology residents and fellows from the Neurology Residency
      Review Committee (NRRC).

PMID- 15249652
TI  - Duty hours vs professional ethics: ACGME rules create conflicts.

PMID- 15249653
TI  - Multi-detector row CT for depicting anatomic features of cephalothoracopagus
      varieties: revised approach.
AB  - Conjoined twins can be classified on the basis of the site of union; thus, three
      main types can be described: (a) ventral union, (b) dorsal union, and (c) rarer
      forms of union. Ventral union is characterized by the fusion of the two embryos
      on the ventral side (eg, the abdomen). Dorsal union twins are joined on the
      dorsal aspect (eg, the vertebral column or occipital bone). Ventral union twins
      include the group of crucipage twins (ventral midline structures at 90 degrees to
      the dorsal midline structures), which show interesting features in the
      organization of the midline. Twins conjoined at the head and chest are called
      cephalothoracopagus twins. The cephalothoracopagus variety called "Janus" is
      characterized by the presence of two opposite faces, which are composite
      structures half of which belong to one twin and half to the other. A complete set
      of five variants of cephalothoracopagus is presented and, to the authors'
      knowledge, analyzed for the first time with multi-detector row helical computed
      tomography. This modality is an invaluable tool for obtaining high-resolution
      images of the brain, chest, abdomen, and spine and for demonstrating organ
      position, shared viscera, and limited vascular anatomy. In addition, data
      acquired in three-dimensional volumes can further be manipulated and then
      reconstructed. For this purpose, the authors developed dedicated software for
      three-dimensional reconstruction to analyze data from specimens preserved in
      formalin. The anatomic findings are discussed here for their embryologic value
      and to revise the classification of cephalothoracopagus twins. These data offer
      detailed information for accurate comprehension of imaging studies and for
      theoretical studies concerning the formation of several anatomic structures.

PMID- 15249655
TI  - Met provides essential signals for liver regeneration.
AB  - Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine
      kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF),
      in development of the liver, muscle, and placenta. Here, we use conditional
      mutagenesis in mice to analyze the function of Met during liver regeneration,
      using the Mx-cre transgene to introduce the mutation in the adult. After partial
      hepatectomy in mice carrying the Mx-cre-induced Met mutation, regeneration of the
      liver is impaired. Comparison of signal transduction pathways in control and
      mutant livers indicates that Met and other signaling receptors cooperate to fully
      activate particular signaling molecules, for instance, the protein kinase Akt.
      However, activation of the Erk1/2 kinase during liver regeneration depends
      exclusively on Met. Signaling crosstalk is thus an important aspect of the
      regulation of liver regeneration. Analysis of cell cycle progression of
      hepatocytes in conditional Met mutant mice indicates a defective exit from
      quiescence and diminished entry into S phase. Impaired liver regeneration is
      accompanied by compensatory physiological responses that include prolonged up
      regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that the
      HGF/SF/Met signaling system is essential not only during liver development but
      also for the regeneration of the organ in the adult.

PMID- 15249654
TI  - Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces
      atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein
      E.
AB  - Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid
      differentiation factor 88 (MyD88) play an essential role in the innate immune
      responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is
      associated with a significant reduction of aortic plaque areas in atherosclerosis
      prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia,
      implying an important role for the innate immune system in atherogenesis.
      Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated
      reduced aortic atherosclerosis that was associated with reductions in circulating
      levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1,
      plaque lipid content, numbers of macrophage, and cyclooxygenase 2
      immunoreactivity in their plaques. Endothelial-leukocyte adhesion in response to
      minimally modified low-density lipoprotein was reduced in aortic endothelial
      cells derived from MyD88-deficient mice. Taken together, our results suggest an
      important role for TLR4 and MyD88 signaling in atherosclerosis in a
      hypercholesterolemic mouse model, providing a pathophysiologic link between
      innate immunity, inflammation, and atherogenesis.

PMID- 15249656
TI  - An alternative agriculture system is defined by a distinct expression profile of
      select gene transcripts and proteins.
AB  - Conventional agriculture has relied heavily on chemical inputs that have
      negatively impacted the environment and increased production costs. Transition to
      agricultural sustainability is a major challenge and requires that alternative
      agricultural practices are scientifically analyzed to provide a sufficiently
      informative knowledge base in favor of alternative farming practices. We show a
      molecular basis for delayed leaf senescence and tolerance to diseases in tomato
      plants cultivated in a legume (hairy vetch) mulch-based alternative agricultural
      system. In the hairy vetch-cultivated plants, expression of specific and select
      classes of genes is up-regulated compared to those grown on black polyethylene
      mulch. These include N-responsive genes such as NiR, GS1, rbcL, rbcS, and G6PD;
      chaperone genes such as hsp70 and BiP; defense genes such as chitinase and
      osmotin; a cytokinin-responsive gene CKR; and gibberellic acid 20 oxidase. We
      present a model of how their protein products likely complement one another in a
      field scenario to effect efficient utilization and mobilization of C and N,
      promote defense against disease, and enhance longevity.

PMID- 15249657
TI  - Discovery of antivirals against smallpox.

PMID- 15249659
TI  - An amyloid-forming segment of beta2-microglobulin suggests a molecular model for
      the fibril.
AB  - In humans suffering from dialysis-related amyloidosis, the protein beta2
      microglobulin (beta2M) is deposited as an amyloid; however, an amyloid of beta2M
      is unknown in mice. beta2M sequences from human and mouse are 70% identical, but
      there is a seven-residue peptide in which six residues differ. This peptide from
      human beta2M forms amyloid in vitro, whereas the mouse peptide does not.
      Substitution of the human peptide for its counterpart in the mouse sequence
      results in the formation of amyloid in vitro. These results show that a seven
      residue segment of human beta2M is sufficient to convert beta2M to the amyloid
      state, and that specific residue interactions are crucial to the conversion.
      These observations are consistent with a proposed Zipper-spine model for beta2M
      amyloid, in which the spine of the fibril consists of an anhydrous beta-sheet.

PMID- 15249658
TI  - Selective disruption of PPARgamma 2 impairs the development of adipose tissue and
      insulin sensitivity.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that plays a pivotal role in obesity and diabetes. PPARgamma has two
      isoforms, PPARgamma1 and PPARgamma2. We investigated the functional differences
      between PPARgamma1 and PPARgamma2 by selectively disrupting PPARgamma2 in mice.
      In contrast to the embryonic lethality of PPARgamma-deficient mice, PPARgamma2(-/
      ) mice survived. Although normal development was identified in other tissues we
      examined, PPARgamma2(-/-) mice exhibited an overall reduction in white adipose
      tissue, less lipid accumulation, and decreased expression of adipogenic genes in
      adipose tissue. In addition, insulin sensitivity was impaired in male PPARgamma2(
      /-) mice, with dramatically decreased expression of insulin receptor substrate 1
      and glucose transporter 4 in the skeletal muscle, but thiazolidinediones were
      able to normalize this insulin resistance. Consistent with in vivo data,
      PPARgamma2(-/-) mouse embryonic fibroblasts showed a dramatically reduced
      capacity for adipogenesis in vitro compared with wild-type mouse embryonic
      fibroblasts. Taken together, our data demonstrate that PPARgamma2 deficiency
      impairs the development of adipose tissue and insulin sensitivity. PPARgamma2(-/
      ) mice may provide a tool to study the role of PPARgamma2 in obesity and
      diabetes.

PMID- 15249660
TI  - Tree-structured supervised learning and the genetics of hypertension.
AB  - This paper is about an algorithm, FlexTree, for general supervised learning. It
      extends the binary tree-structured approach (Classification and Regression Trees,
      CART) although it differs greatly in its selection and combination of predictors.
      It is particularly applicable to assessing interactions: gene by gene and gene by
      environment as they bear on complex disease. One model for predisposition to
      complex disease involves many genes. Of them, most are pure noise; each of the
      values that is not the prevalent genotype for the minority of genes that
      contribute to the signal carries a "score." Scores add. Individuals with scores
      above an unknown threshold are predisposed to the disease. For the additive score
      problem and simulated data, FlexTree has cross-validated risk better than many
      cutting-edge technologies to which it was compared when small fractions of
      candidate genes carry the signal. For the model where only a precise list of
      aberrant genotypes is predisposing, there is not a systematic pattern of absolute
      superiority; however, overall, FlexTree seems better than the other technologies.
      We tried the algorithm on data from 563 Chinese women, 206 hypotensive, 357
      hypertensive, with information on ethnicity, menopausal status, insulin-resistant
      status, and 21 loci. FlexTree and Logic Regression appear better than the others
      in terms of Bayes risk. However, the differences are not significant in the usual
      statistical sense.

PMID- 15249661
TI  - Primate jumping genes elucidate strepsirrhine phylogeny.
AB  - Transposable elements provide a highly informative marker system for analyzing
      evolutionary histories. To solve controversially discussed topics in
      strepsirrhine phylogeny, we characterized 61 loci containing short interspersed
      elements (SINEs) and determined the SINE presence-absence pattern at orthologous
      loci in a representative strepsirrhine panel. This SINE monolocus study was
      complemented by a Southern blot analysis tracing multiple loci of two different
      strepsirrhine specific SINEs. The results thereof were combined with phylogenetic
      trees reconstructed on the basis of complete mitochondrial cytochrome b sequences
      from all recognized strepsirrhine genera. Here we present evidence for (i) a
      sister group relationship of Malagasy Chiromyiformes and Lemuriformes, (ii)
      Lorisidae being a monophyletic sister clade to the Galagidae, and (iii) common
      ancestry of African and Asian lorisids. Based on these findings, we conclude that
      strepsirrhines originated in Africa and that Madagascar and Asia were colonized
      by respective single immigration events. In agreement with paleocontinental data,
      the molecular analyses suggest a crossing of the Mozambique channel by rafting
      between the late Cretaceous and the middle Eocene, whereas Asia was most likely
      colonized between the early Eocene and the middle Oligocene on a continental
      route. Furthermore, one SINE integration links the two Lemuriformes families,
      Lemuridae and Indriidae, indicating a common origin of diurnality or
      cathemerality and a later reversal to nocturnality by the indriid genus Avahi.

PMID- 15249662
TI  - Development of a cancer DNA phenotype prior to tumor formation.
AB  - Using the carcinogen 3-methylcholanthrene (MCA), we demonstrate with Fourier
      transform-infrared spectroscopy that a cancer DNA phenotype is produced well in
      advance of palpable tumors. We further demonstrate that the administration of
      cyclophosphamide markedly inhibits the development of the cancer phenotype and
      concomitantly delays tumor formation. MCA, injected into the hind legs of mice,
      produced a variety of significant structural changes in the nucleotide bases and
      phosphodiester-deoxyribose backbone, as reflected in a substantial (34%)
      difference between the mean DNA spectra of the control and the MCA-injected mice.
      Strikingly, 57 days before the mean appearance of tumors, we could not
      distinguish the DNA structure of the histologically normal tissues of the MCA
      injected mice from the DNA structure of the tumor tissues. This finding indicates
      the early development of a cancer phenotype. Confirmatory evidence was obtained
      when tissues from a group of mice injected with both MCA and cyclophosphamide did
      not manifest the cancer phenotype, and their mean DNA structure closely resembled
      that of the control mice. Accordingly, we propose that the cancer DNA phenotype,
      as evinced by Fourier transform-infrared spectroscopy, is a promising early
      indicator of tumor formation, and we postulate that agents capable of inhibiting
      this phenotype may delay or prevent carcinogenesis.

PMID- 15249663
TI  - A rare-cell detector for cancer.
AB  - Although a reliable method for detection of cancer cells in blood would be an
      important tool for diagnosis and monitoring of solid tumors in early stages,
      current technologies cannot reliably detect the extremely low concentrations of
      these rare cells. The preferred method of detection, automated digital microscopy
      (ADM), is too slow to scan the large substrate areas. Here we report an approach
      that uses fiber-optic array scanning technology (FAST), which applies laser
      printing techniques to the rare-cell detection problem. With FAST cytometry,
      laser-printing optics are used to excite 300,000 cells per sec, and emission is
      collected in an extremely wide field of view, enabling a 500-fold speed-up over
      ADM with comparable sensitivity and superior specificity. The combination of FAST
      enrichment and ADM imaging has the performance required for reliable detection of
      early-stage cancer in blood.

PMID- 15249664
TI  - Requirement of matrix metalloproteinase-9 for the transformation of human mammary
      epithelial cells by Stat3-C.
AB  - Persistently activated Stat3 is found in many different cancers, including
      approximately 60% of breast tumors. Here, we demonstrate that a constitutively
      activated Stat3 transforms immortalized human mammary epithelial cells and that
      this oncogenic event requires the activity of matrix metalloproteinase-9 (MMP-9).
      By immunohistochemical analysis, we observe a positive correlation between strong
      MMP-9 expression and tyrosine phosphorylated Stat3 in primary breast cancer
      specimens. These results demonstrate a relationship between activated Stat3 and
      MMP-9 in breast oncogenesis.

PMID- 15249665
TI  - Bipolar orientation of chromosomes in Saccharomyces cerevisiae is monitored by
      Mad1 and Mad2, but not by Mad3.
AB  - The spindle checkpoint governs the timing of anaphase separation of sister
      chromatids. In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required
      for arrest in the presence of damage induced by antimicrotubule drugs or
      catastrophic loss of spindle structure. We find that the MAD genes are not
      equally required for robust growth in the presence of more subtle kinetochore and
      microtubule damage. A mad1Delta synthetic lethal screen identified 16 genes whose
      deletion in cells lacking MAD1 results in death or slow growth. Eleven of these
      mad1Delta genetic interaction partners encode proteins at the kinetochore
      microtubule interface. Analysis of the entire panel revealed similar phenotypes
      in combination with mad2Delta. In contrast, 13 panel mutants exhibited a less
      severe phenotype in combination with mad3Delta. Checkpoint arrest in the absence
      of bipolar orientation and tension (induced by replication block in a cdc6
      mutant) was lacking in cells without MAD1 or MAD2. Cells without MAD3 were
      checkpoint-proficient. We conclude that Mad1 and Mad2 are required to detect
      bipolar orientation and/or tension at kinetochores, whereas Mad3 is not.

PMID- 15249666
TI  - A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of
      rheumatoid arthritis.
AB  - The hallmark of rheumatoid arthritis (RA) is the progressive destruction of
      articular joints, characterized by invasive synovial hyperplasia and pathological
      neovascularization. Here we report that PPI-2458, a member of the fumagillin
      class of irreversible methionine aminopeptidase-2 (MetAP-2) inhibitors, potently
      inhibits the proliferation of human fibroblast-like synoviocytes (HFLS-RA),
      derived from RA patients, with a growth inhibitory concentration 50 (GI(50)) of
      0.04 nM and a maximum inhibition of >95% at 1 nM. Human umbilical vein
      endothelial cells (HUVEC) are similarly inhibited in proliferation by PPI-2458
      (GI(50), 0.2 nM). We developed a method to measure the level of MetAP-2 enzyme
      inhibition after exposure to PPI-2458 and demonstrate that growth inhibition of
      PPI-2458-sensitive HFLS-RA and HUVEC is linked to MetAP-2 enzyme inhibition, in a
      dose-dependent fashion. The secretion of several inflammatory mediators such as
      IL-6 and vascular endothelial growth factor from activated HFLS-RA was not
      inhibited by PPI-2458. The CNS toxicity profile of PPI-2458, determined by the
      incidence of seizures, is significantly improved over that of the parental
      compound TNP-470. In the rat model of peptidoglycan-polysaccharide-induced
      arthritis, PPI-2458 significantly attenuated paw swelling when therapeutically
      administered after the onset of chronic disease. We suggest that the mechanism of
      PPI-2458 action, highly selective and potent anti-proliferative activity on HFLS
      RA and HUVEC in vitro, a significantly improved CNS toxicity profile, and marked
      attenuation of chronic disease in the rat peptidoglycan-polysaccharide arthritis
      model in vivo, positions this compound as a drug for the treatment of RA.

PMID- 15249667
TI  - The Arabidopsis AtRAD51 gene is dispensable for vegetative development but
      required for meiosis.
AB  - The maintenance of genome integrity and the generation of biological diversity
      are important biological processes, and both involve homologous recombination. In
      yeast and animals, homologous recombination requires the function of the RAD51
      recombinase. In vertebrates, RAD51 seems to have acquired additional functions in
      the maintenance of genome integrity, and rad51 mutations cause lethality, but it
      is not clear how widely these functions are conserved among eukaryotes. We report
      here a loss-of-function mutant in the Arabidopsis homolog of RAD51, AtRAD51. The
      atrad51-1 mutant exhibits normal vegetative and flower development and has no
      detectable abnormality in mitosis. Therefore, AtRAD51 is not necessary under
      normal conditions for genome integrity. In contrast, atrad51-1 is completely
      sterile and defective in male and female meioses. During mutant prophase I,
      chromosomes fail to synapse and become extensively fragmented. Chromosome
      fragmentation is suppressed by atspo11-1, indicating that AtRAD51 functions
      downstream of AtSPO11-1. Therefore, AtRAD51 likely plays a crucial role in the
      repair of DNA double-stranded breaks generated by AtSPO11-1. These results
      suggest that RAD51 function is essential for chromosome pairing and synapsis at
      early stages in meiosis in Arabidopsis. Furthermore, major aspects of meiotic
      recombination seem to be conserved between yeast and plants, especially the fact
      that chromosome pairing and synapsis depend on the function of SPO11 and RAD51.

PMID- 15249668
TI  - Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and
      relationship to in vivo function.
AB  - Aminophospholipid translocases (APLTs) are defined primarily by their ability to
      flip fluorescent or spin-labeled derivatives of phosphatidylserine (PS) and
      phosphatidylethanolamine (PE) from the external leaflet of a membrane bilayer to
      the cytosolic leaflet and are thought to establish phospholipid asymmetry in
      biological membranes. The identities of APLTs remain unknown, although candidate
      proteins include the Drs2p/ATPase II subfamily of P-type ATPases. Drs2p from
      budding yeast localizes to the trans-Golgi network (TGN), and here we show that
      this membrane contains an ATP-dependent APLT that flips 7-nitro-2-1,3
      benzoxadiazol-4-yl (NBD) PS and PE derivatives from the luminal to the cytosolic
      leaflet. To assess the contribution of Drs2p to this activity, TGN membranes were
      prepared from strains harboring WT or temperature-sensitive alleles of DRS2 and
      null alleles of three other potential APLT genes (DNF1, DNF2, and DNF3). Assay of
      these membranes indicated that Drs2p was required for the ATP-dependent
      translocation of NBD-PS, whereas no active translocation of NBD-PE or NBD
      phosphatidylcholine was detected. The specificity of Drs2p for NBD-PS suggested
      that translocation of PS would be required for the function of Drs2p in protein
      transport from the TGN. However, cho1 yeast strains that are unable to synthesize
      PS do not phenocopy drs2 but instead transport proteins normally via the
      secretory pathway. In addition, a drs2 cho1 double mutant retains drs2 transport
      defects. Therefore, whereas NBD-PS is a preferred substrate for Drs2p in vitro,
      endogenous PS is not an obligatory substrate in vivo for the role Drs2p plays in
      protein transport.

PMID- 15249669
TI  - Structure of HIV-1 reverse transcriptase bound to an inhibitor active against
      mutant reverse transcriptases resistant to other nonnucleoside inhibitors.
AB  - We have determined the crystal structure of the HIV type 1 reverse transcriptase
      complexed with CP-94,707, a new nonnucleoside reverse transcriptase inhibitor
      (NNRTI), to 2.8-A resolution. In addition to inhibiting the wild-type enzyme,
      this compound inhibits mutant enzymes that are resistant to inhibition by
      nevirapine, efavirenz, and delaviridine. In contrast to other NNRTI complexes
      where tyrosines 181 and 188 are pointing toward the enzyme active site, the
      binding pocket in this complex has the tyrosines pointing the opposite direction,
      as in the unliganded protein structure, to accommodate CP-94,707. This
      conformation of the pocket has not been observed previously in NNRTI complexes
      and substantially alters the shape and surface features that are available for
      interactions with the inhibitor. One ring of CP-94,707 makes extensive stacking
      interactions with tryptophan 229, one of the few residues in the NNRTI-binding
      pocket that cannot readily mutate to give rise to drug resistance. In this
      conformation of the pocket, mutations of tyrosines 181 and 188 are less likely to
      disrupt inhibitor binding. Modeling the asparagine mutation of lysine 103 shows
      that a hydrogen bond between it and tyrosine 188 could form as readily in the CP
      94,707 complex as it does in the apoenzyme structure, providing an explanation
      for the activity of this inhibitor against this clinically important mutant.

PMID- 15249671
TI  - Harnessing new science is vital for biodefense and global health.

PMID- 15249670
TI  - Heterodimeric complexes of Hop2 and Mnd1 function with Dmc1 to promote meiotic
      homolog juxtaposition and strand assimilation.
AB  - Saccharomyces cerevisiae Hop2 and Mnd1 are abundant meiosisspecific chromosomal
      proteins, and mutations in the corresponding genes lead to defects in meiotic
      recombination and in homologous chromosome interactions during mid-prophase.
      Analysis of various double mutants suggests that HOP2, MND1, and DMC1 act in the
      same genetic pathway for the establishment of close juxtaposition between
      homologous meiotic chromosomes. Biochemical studies indicate that Hop2 and Mnd1
      proteins form a stable heterodimer with a higher affinity for double-stranded
      than single-stranded DNA, and that this heterodimer stimulates the strand
      assimilation activity of Dmc1 in vitro. Together, the genetic and biochemical
      results suggest that Hop2, Mnd1, and Dmc1 are functionally interdependent during
      meiotic DNA recombination.

PMID- 15249672
TI  - Magnetic circular dichroism of peralkylated tetrasilane conformers.
AB  - Magnetic circular dichroism (MCD) of five peralkylated tetrasilanes (1-5)
      conformationally constrained to angles ranging from nearly 0 degrees to 180
      degrees and of the open chain tetrasilane Si(4)Me(10) (6) shows a clear
      conformational dependence and permits the detection of previously hidden
      transitions. In the tetrasilane CH(2)Si(4)Me(8) (1), with the smallest dihedral
      angle, comparison of MCD with absorption spectra reveals four low-energy
      electronic transitions. In the tetrasilanes 2-4, three distinct transitions are
      apparent. In tetrasilanes 5 and 6, MCD reveals the very weak transition that has
      been predicted to be buried under the first intense peak and to which the
      anomalous thermochromism of 6 and other short-chain oligosilanes has been
      attributed.

PMID- 15249673
TI  - Surviving the ice: Northern refugia and postglacial colonization.
AB  - The contemporary distribution of biological diversity cannot be understood
      without knowledge of how organisms responded to the geological and climatic
      history of Earth. In particular, Quaternary expansions and contractions of
      glacial ice sheets are thought to have played an important role in shaping the
      distribution of biodiversity among current populations in the north-temperate
      region. In the central U.S., fossil and palynological data provide support for
      the maintenance of a large southeastern refuge during the last glacial maximum,
      and many temperate organisms are believed to have responded to glacial expansion
      by shifting their ranges to southern refugia and recolonizing northward to track
      the receding ice sheets. Thus, organisms are assumed to track favorable climates,
      and species ranges are expected to have shifted significantly. Here we present
      data from a deciduous forest vertebrate, the eastern chipmunk (Tamias striatus)
      in the central U.S., indicating the maintenance of multiple refugial sources as
      well as a southward expansion from a northern refugium. These results challenge
      the view that, during glacial maxima, organisms must have migrated south out of
      their ranges to track favorable climates.

PMID- 15249675
TI  - PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and
      host tissues negatively regulates T cells.
AB  - Both positive and negative regulatory roles have been suggested for the B7 family
      member PD-L1(B7-H1). PD-L1 is expressed on antigen-presenting cells (APCs),
      activated T cells, and a variety of tissues, but the functional significance of
      PD-L1 on each cell type is not yet clear. To dissect the functions of PD-L1 in
      vivo, we generated PD-L1-deficient (PD-L1(-/-)) mice. CD4(+) and CD8(+) T cell
      responses were markedly enhanced in PD-L1(-/-) mice compared with wild-type mice
      in vitro and in vivo. PD-L1(-/-) dendritic cells stimulated greater wild-type
      CD4(+) T cell responses than wild-type dendritic cells, and PD-L1(-/-) CD4(+) T
      cells produced more cytokines than wild-type CD4(+) T cells in vitro,
      demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8(+) T
      cell responses also were significantly enhanced, indicating that PD-L1 has a role
      in limiting the expansion or survival of CD8(+) T cells. Studies using the myelin
      oligodendrocyte model of experimental autoimmune encephalomyelitis showed that PD
      L1 on T cells and in host tissues limits responses of self-reactive CD4(+) T
      cells in vivo. PD-L1 deficiency converted the 129S4/SvJae strain from a resistant
      to experimental autoimmune encephalomyelitis-susceptible strain. Transfer of
      encephalitogenic T cells from wild-type mice into PD-L1(-/-) recipients led to
      exacerbated disease. Disease was even more severe in PD-L1(-/-) recipients of PD
      L1(-/-) T cells. These results demonstrate that PD-L1 on T cells, APCs, and host
      tissue inhibits naive and effector T cell responses and plays a critical role in
      T cell tolerance.

PMID- 15249676
TI  - Snow conditions may create an invisible barrier for lynx.
AB  - The dynamics of Canadian lynx (Lynx canadensis) abundance are geographically
      structured according to the influence of large-scale climatic regimes. Here we
      demonstrate that this structuring matches zones of differential snow conditions,
      in particular surface hardness, as determined by the frequency of winter warm
      spells. Through a modified functional response curve, we show that various
      features of the snow may influence lynx interaction with its main prey species,
      the snowshoe hare (Lepus americanus). This study highlights the importance of
      snow, and exemplifies how large-scale climatic fluctuations can mechanistically
      influence population biological patterns.

PMID- 15249677
TI  - O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in
      Alzheimer's disease.
AB  - Microtubule-associated protein tau is abnormally hyperphosphorylated and
      aggregated into neurofibrillary tangles in brains of individuals with Alzheimer's
      disease (AD) and other tauopathies. Tau pathology is critical to pathogenesis and
      correlates to the severity of dementia. However, the mechanisms leading to
      abnormal hyperphosphorylation are unknown. Here, we demonstrate that human brain
      tau was modified by O-GlcNAcylation, a type of protein O-glycosylation by which
      the monosaccharide beta-N-acetylglucosamine (GlcNAc) attaches to serine/threonine
      residues via an O-linked glycosidic bond. O-GlcNAcylation regulated
      phosphorylation of tau in a site-specific manner both in vitro and in vivo. At
      most of the phosphorylation sites, O-GlcNAcylation negatively regulated tau
      phosphorylation. In an animal model of starved mice, low glucose
      uptake/metabolism that mimicked those observed in AD brain produced a decrease in
      O-GlcNAcylation and consequent hyperphosphorylation of tau at the majority of the
      phosphorylation sites. The O-GlcNAcylation level in AD brain extracts was
      decreased as compared to that in controls. These results reveal a mechanism of
      regulation of tau phosphorylation and suggest that abnormal hyperphosphorylation
      of tau could result from decreased tau O-GlcNAcylation, which probably is induced
      by deficient brain glucose uptake/metabolism in AD and other tauopathies.

PMID- 15249678
TI  - REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human
      medulloblastoma.
AB  - Hedgehog signaling is suggested to be a major oncogenic pathway in
      medulloblastoma, which arises from aberrant development of cerebellar granule
      progenitors. Allelic loss of chromosome 17p has also been described as the most
      frequent genetic defect in this human neoplasia. This observation raises the
      question of a possible interplay between 17p deletion and the Hedgehog
      tumorigenic pathway. Here, we identify the human orthologue of mouse REN(KCTD11),
      previously reported to be expressed in differentiating and low proliferating
      neuroblasts. Human REN(KCTD11) maps to 17p13.2 and displays allelic deletion as
      well as significantly reduced expression in medulloblastoma. REN(KCTD11) inhibits
      medulloblastoma cell proliferation and colony formation in vitro and suppresses
      xenograft tumor growth in vivo. REN(KCTD11) seems to inhibit medulloblastoma
      growth by negatively regulating the Hedgehog pathway because it antagonizes the
      Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear
      transfer, and its growth inhibitory activity is impaired by Gli1 inactivation.
      Therefore, we identify REN(KCTD11) as a suppressor of Hedgehog signaling and
      suggest that its inactivation might lead to a deregulation of the tumor-promoting
      Hedgehog pathway in medulloblastoma.

PMID- 15249679
TI  - The mitochondrial genome of Paraspadella gotoi is highly reduced and reveals that
      chaetognaths are a sister group to protostomes.
AB  - We report the complete mtDNA sequence from a member of the phylum Chaetognatha
      (arrow worms). The Paraspadella gotoi mtDNA is highly unusual, missing 23 of the
      genes commonly found in animal mtDNAs, including atp6, which has otherwise been
      found universally to be present. Its 14 genes are unusually arranged into two
      groups, one on each strand. One group is punctuated by numerous noncoding
      intergenic nucleotides although the other group is tightly packed, having no
      noncoding nucleotides, leading to speculation that there are two transcription
      units with differing modes of expression. The phylogenetic position of the
      Chaetognatha within the Metazoa has long been uncertain, with conflicting or
      equivocal results from various morphological analyses and rRNA sequence
      comparisons. Comparisons here of amino acid sequences from mitochondrially
      encoded proteins give a single most parsimonious tree that supports a position of
      Chaetognatha as sister to the protostomes studied here. From this analysis, one
      can more clearly interpret the patterns of evolution of various developmental
      features, especially regarding the embryological fate of the blastopore.

PMID- 15249680
TI  - Somatolactin selectively regulates proliferation and morphogenesis of neural
      crest derived pigment cells in medaka.
AB  - Species-specific colors and patterns on animal body surfaces are determined
      primarily by neural-crest-derived pigment cells in the skin (chromatophores).
      However, even closely related species display widely differing patterns. These
      contrasting aspects of chromatophores (i.e., the fixed developmental control
      within species and extreme diversity among species) seem to be a curious and
      suitable subject for understanding evolution and diversity of organisms. Here we
      identify a gene responsible for medaka "color interfere" mutants by positional
      cloning. These mutants do not show any obvious morphological and physiological
      defects other than defects in chromatophore proliferation and morphogenesis. The
      mutation has been identified as an 11-base deletion in somatolactin, which causes
      truncation 91 aa upstream of the C terminus of the protein's 230 aa. Somatolactin
      transcription changed dramatically during morphological body color adaptation to
      different backgrounds. This genetic evidence explains somatolactin function.
      Studying this mutant will provide further insights into the development and
      regulation of chromatophores and clues for reassessing other functions of
      somatolactin suggested in other fish.

PMID- 15249681
TI  - Loss of locus coeruleus neurons and reduced startle in parkin null mice.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      and is characterized pathologically by degeneration of catecholaminergic neurons
      of the substantia nigra pars compacta and locus coeruleus, among other regions.
      Autosomal-recessive juvenile Parkinsonism (ARJP) is caused by mutations in the
      PARK2 gene coding for parkin and constitutes the most common familial form of PD.
      The majority of ARJP-associated parkin mutations are thought to be loss of
      function-mutations; however, the pathogenesis of ARJP remains poorly understood.
      Here, we report the generation of parkin null mice by targeted deletion of parkin
      exon 7. These mice show a loss of catecholaminergic neurons in the locus
      coeruleus and an accompanying loss of norepinephrine in discrete regions of the
      central nervous system. Moreover, there is a dramatic reduction of the
      norepinephrine-dependent startle response. The nigrostriatal dopaminergic system
      does not show any impairment. This mouse model will help gain a better
      understanding of parkin function and the mechanisms underlying parkin-associated
      PD.

PMID- 15249682
TI  - Pattern of polymorphism after strong artificial selection in a domestication
      event.
AB  - The process of strong artificial selection during a domestication event is
      modeled, and its effect on the pattern of DNA polymorphism is investigated. The
      model also considers population bottleneck during domestication. Artificial
      selection during domestication is different from a regular selective sweep
      because artificial selection acts on alleles that may have been neutral variants
      before domestication. Therefore, the fixation of such a beneficial allele does
      not always wipe out DNA variation in the surrounding region. The amount by which
      variation is reduced largely depends on the initial frequency of the beneficial
      allele, p. As a consequence, p has a strong effect on the likelihood of detecting
      the signature of selection during domestication from patterns of polymorphism.
      These theoretical results are discussed in light of data collected from maize.
      Although the main focus of this article is on domestication, this model can also
      be generalized to describe selective sweeps from standing genetic variation.

PMID- 15249683
TI  - Binding of platelet glycoprotein Ibalpha to von Willebrand factor domain A1
      stimulates the cleavage of the adjacent domain A2 by ADAMTS13.
AB  - von Willebrand factor (vWF) is a multimeric plasma glycoprotein with three tandem
      A domains. Domains A1 and A3 bind to platelet glycoprotein Ibalpha (GPIbalpha)
      and collagen, respectively. Domain A2 contains the Tyr-1605-Met-1606 bond that is
      cleaved by the metalloprotease ADAMTS13, and this reaction inhibits platelet
      thrombus growth. Fluid shear stress increases the rate of cleavage, suggesting
      that productive interaction with ADAMTS13 requires conformational changes within
      or near domain A2. The influence of the adjacent A1 and A3 domains was assessed
      by mutagenesis of a recombinant substrate consisting of domains A1A2A3. Deletion
      of domain A3 did not affect cleavage by ADAMTS13, whereas deletion of domain A1
      increased the rate of cleavage approximately 10-fold. Similar effects were
      observed with plasma ADAMTS13 and recombinant ADAMTS13 truncated after the spacer
      domain. Digestion of A1A2A3 by plasma ADAMTS13 was enhanced to a similar extent
      by a recombinant mutant fragment of platelet GPIbalpha that binds with high
      affinity to domain A1 or by heparin. Heparin also increased the digestion of
      purified plasma vWF. Neither GPIbalpha nor heparin increased the cleavage of
      substrate A2A3 that lacks domain A1. The results suggest that vWF domain A1
      inhibits the cleavage of domain A2, and that inhibition can be relieved by
      interaction of domain A1 with platelet GPIbalpha or certain glycosaminoglycans.
      Thus, binding of vWF to its major physiological ligands may promote the feedback
      inhibition of platelet adhesion by stimulating the cleavage of domain A2 by
      ADAMTS13 independent of fluid shear stress.

PMID- 15249684
TI  - Essential role of brain-derived neurotrophic factor in adult hippocampal
      function.
AB  - Brain-derived neurotrophic factor (BDNF) regulates neuronal development and
      function. However, it has been difficult to discern its role in the adult brain
      in influencing complex behavior. Here, we use a recently developed inducible
      knockout system to show that deleting BDNF in broad forebrain regions of adult
      mice impairs hippocampal-dependent learning and long-term potentiation. We use
      the inducible nature of this system to show that the loss of BDNF during earlier
      stages of development causes hyperactivity and more pronounced hippocampal
      dependent learning deficits. We also demonstrate that the loss of forebrain BDNF
      attenuates the actions of desipramine, an antidepressant, in the forced swim
      test, suggesting the involvement of BDNF in antidepressant efficacy. These
      results establish roles for BDNF in the adult, and demonstrate the strength of
      this inducible knockout system in studying gene function in the adult brain.

PMID- 15249685
TI  - Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of
      TRIM5alpha.
AB  - Mammalian cells express several factors that act in a cell-autonomous manner to
      inhibit retrovirus replication. Among these are the Friend virus susceptibility
      factor 1/lentivirus susceptibility factor 1/restriction factor 1 (Ref1) class of
      restriction factors, which block infection by targeting the capsids of diverse
      retroviruses. Here we show that lentivirus susceptibility factor 1 and Ref1 are
      species-specific variants of tripartite interaction motif 5alpha (TRIM5alpha), a
      cytoplasmic body component recently shown to block HIV-1 infection in rhesus
      macaque cells, and can indeed block infection by widely divergent retroviruses.
      Depletion of TRIM5alpha from human cells relieved restriction of N-tropic murine
      leukemia virus (N-MLV), and expression of human TRIM5alpha in otherwise
      nonrestricting cells conferred specific resistance to N-MLV infection, indicating
      that TRIM5alpha is Ref1 or an essential component of Ref1. TRIM5alpha variants
      from humans, rhesus monkeys, and African green monkeys displayed different but
      overlapping restriction specificities that were quite accurately predicted by the
      restriction properties of the cells from which they were derived. All TRIM5alpha
      variants could inhibit infection by at least two different retroviruses, and
      African green monkey TRIM5alpha was able to inhibit infection by no less than
      four divergent retroviruses of human, non-human primate, equine, and murine
      origin. However, each TRIM5alpha variant was unable to restrict retroviruses
      isolated from the same species. These data indicate that TRIM5alpha can confer
      broad innate immunity to retrovirus infection in primate cells and is likely to
      be an important natural barrier to cross-species retrovirus transmission.

PMID- 15249686
TI  - Unique modifications with phosphocholine and phosphoethanolamine define alternate
      antigenic forms of Neisseria gonorrhoeae type IV pili.
AB  - Several major bacterial pathogens and related commensal species colonizing the
      human mucosa express phosphocholine (PC) at their cell surfaces. PC appears to
      impact host-microbe biology by serving as a ligand for both C-reactive protein
      and the receptor for platelet-activating factor. Type IV pili of Neisseria
      gonorrhoeae (Ng) and Neisseria meningitidis, filamentous protein structures
      critical to the colonization of their human hosts, are known to react variably
      with monoclonal antibodies recognizing a PC epitope. However, the structural
      basis for this reactivity has remained elusive. To address this matter, we
      exploited the finding that the PilE pilin subunit in Ng mutants lacking the PilV
      protein acquired the PC epitope independent of changes in pilin primary
      structure. Specifically, we show by using mass spectrometry that PilE derived
      from the pilV background is composed of a mixture of subunits bearing O-linked
      forms of either phosphoethanolamine (PE) or PC at the same residue, whereas the
      wild-type background carries only PE at that same site. Therefore, PilV can
      influence pilin structure and antigenicity by modulating the incorporation of
      these alternative modifications. The disaccharide covalently linked to Ng pilin
      was also characterized because it is present on the same peptides bearing the PE
      and PC modifications and, contrary to previous reports, was found to be linked by
      means of 2,4-diacetamido-2,4,6-trideoxyhexose. Taken together, these findings
      provide new insights into Ng type IV pilus structure and antigenicity and resolve
      long-standing issues regarding the nature of both the PC epitope and the pilin
      glycan.

PMID- 15249687
TI  - The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1
      retroviral restriction factor activities.
AB  - The rhesus macaque tripartite motif containing protein TRIM5alpha specifically
      restricts HIV-1 infection at an early post-entry step before reverse
      transcription [Stremlau, M., Owens, C. M., Perron, M. J., Kiessling, M.,
      Autissier, P. & Sodroski, J. (2004) Nature 427, 848-853]. Here, we show that the
      human and African green monkey (AGM) TRIM5alpha genes encode Ref1 and Lv1
      antiretroviral activities, respectively. Expression of TRIM5alpha in permissive
      cat cells renders them resistant to restriction-sensitive murine leukemia virus
      but not closely related insensitive virus. Disruption of TRIM5alpha expression in
      human and AGM cells with small interfering RNA rescues infectivity of restricted
      virus without affecting unrestricted virus. We also demonstrate that the activity
      of the murine restriction factor Fv1 depends on TRIM5alpha expression when Fv1 is
      expressed in human cells. Furthermore, a drug that modifies the behavior of the
      related promyelocytic leukemia protein PML specifically rescues infection by
      viruses restricted by human TRIM5alpha. Alignment of the TRIM5alpha proteins from
      rhesus macaque and AGM indicates an 18-aa insertion. We speculate that this
      insertion may contribute to the broader specificity of the AGM TRIM5alpha
      restriction as compared with the human and rhesus macaque proteins.

PMID- 15249689
TI  - Chaotic microlasers based on dynamical localization.
AB  - We report the direct observation of lasing action from a dynamically localized
      mode in a microdisk resonator with rough boundary. In contrast to microlasers
      based on stable ray trajectories, the performance of our device is robust with
      respect to the boundary roughness and corresponding ray chaos, taking advantage
      of Anderson localization in angular momentum. The resonator design, although
      demonstrated here in GaAs-InAs microdisk laser, should be applicable to any
      lasers and sensors based on semiconductor or polymer materials.

PMID- 15249688
TI  - The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA
      gene transcription by interacting with upstream binding factor.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized
      by an abnormality of craniofacial development that arises during early
      embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the
      nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS
      have been uncovered, the mechanism underlying its pathogenesis and the function
      of treacle remain unknown. Here, we show that treacle is involved in ribosomal
      DNA gene transcription by interacting with upstream binding factor (UBF).
      Immunofluorescence labeling shows treacle and UBF colocalize to specific
      nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin
      d-treated HeLa cells. Biochemical analysis shows the association of treacle and
      UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both
      suggest physical interaction of the two nucleolar phosphoproteins. Down
      regulation of treacle expression using specific short interfering RNA results in
      inhibition of ribosomal DNA transcription and cell growth. A similar correlation
      is observed in Tcof(+/-) mouse embryos that exhibit craniofacial defects and
      growth retardation. Thus, treacle haploinsufficiency in TCS patients might result
      in abnormal development caused by inadequate ribosomal RNA production in the
      prefusion neural folds during the early stages of embryogenesis. The elucidation
      of a physiological function of treacle provides important information of
      relevance to the molecular dissection of the biochemical pathology of TCS.

PMID- 15249690
TI  - Trim5alpha protein restricts both HIV-1 and murine leukemia virus.
AB  - Replication of HIV-1 and N-tropic murine leukemia virus (N-MLV) is restricted in
      a number of different primate cells. In some cell lines, cross-saturation
      experiments suggest that the two viruses are interacting with the same
      restriction factor. Recently, Trim5alpha protein from rhesus monkey was found to
      restrict HIV-1. We have confirmed this result and have shown that Trim5alpha from
      two African green monkey cell lines, Vero and CV-1, also restricts HIV-1. In
      addition, we show that human, rhesus, and African green monkey Trim5alpha can
      restrict N-MLV. By using a panel of MLV capsid mutants, subtle differences in the
      anti-MLV activity were identified among the different primate Trim5alpha cDNAs.
      Trim1 isolated from humans and green monkeys was also found to restrict N-MLV. We
      hypothesize that the Trim family of proteins plays a widespread role in innate
      immunity to viral infection.

PMID- 15249691
TI  - Maximising the global use of HIV surveillance data through the development and
      sharing of analytical tools.

PMID- 15249692
TI  - The UNAIDS Estimation and Projection Package: a software package to estimate and
      project national HIV epidemics.
AB  - This paper describes the Estimation and Projection Package (EPP) for estimating
      and projecting HIV prevalence levels in countries with generalised epidemics. The
      paper gives an overall summary of the software and interface. It describes the
      process of defining and modelling a national epidemic in terms of locally
      relevant sub-epidemics and the four epidemiological parameters used to fit a
      curve to produce the prevalence trends in the epidemic. It also provides an
      example of using the EPP in a country with a generalised epidemic. The paper
      discusses the strengths and weaknesses of the software and its envisaged future
      developments.

PMID- 15249693
TI  - The workbook approach to making estimates and projecting future scenarios of
      HIV/AIDS in countries with low level and concentrated epidemics.
AB  - This paper describes an approach to making estimates and short term projections
      of future scenarios of HIV/AIDS in countries with low level and concentrated
      epidemics. This approach focuses on identifying populations which through their
      behaviour are at higher risk of infection with HIV or who are exposed through the
      risk behaviour of their sexual partners. Estimates of the size and HIV prevalence
      of these populations allow the total number of HIV infected people in a country
      or region to be estimated. Subsequently, assumptions about the possible level and
      timing of saturation of HIV prevalence among each population can be used to
      explore future scenarios of HIV prevalence. The basic structure of the software
      used to make estimates and projections is described. This software includes a set
      of consistency and audit checks to help exclude unrealistic projections. The
      paper also discusses the strengths and weakness to this approach to making
      estimates and projections of HIV/AIDS in countries with low level and
      concentrated epidemics.

PMID- 15249694
TI  - Projecting the demographic consequences of adult HIV prevalence trends: the
      Spectrum Projection Package.
AB  - This paper describes the software package Spectrum, which is a modular program
      that is used to examine the consequences of current trends and future program
      interventions in reproductive health. It is used to determine the consequences of
      the HIV/AIDS epidemic, including the number of people living with HIV/AIDS by age
      and sex, the number of AIDS deaths, and the number of orphans as a result of
      AIDS, as well as other demographic indicators of interest, such as life
      expectancy and <5 mortality. The core of Spectrum is a demographic projection
      model called DemProj, which projects the population by age and sex. Other modules
      interact with the demographic projection. The HIV/AIDS projections are added to
      the demographic projections using a module called AIDS Impact Model. This module
      uses the projection of adult HIV prevalence over time, which is prepared using
      the Estimation and Projection Package model or the projection workbook. It also
      requires assumptions about the epidemiology of HIV, including the ratio of
      female:male prevalence, the distribution of infection by age, the distribution of
      the time from infection until AIDS death, and the effect of HIV on fertility.

PMID- 15249695
TI  - The Asian Epidemic Model: a process model for exploring HIV policy and programme
      alternatives in Asia.
AB  - Process models offer opportunities to explore the effectiveness of different
      programme and policy alternatives by varying input behaviours and model
      parameters to reflect programmatic/policy effects. The Asian Epidemic Model (AEM)
      has been designed to reflect the primary groups and transmission modes driving
      HIV transmission in Asia. The user adjusts AEM fitting parameters until HIV
      prevalence outputs from the model agree with observed epidemiological trends. The
      AEM resultant projections are closely tied to the epidemiological and behavioural
      data in the country. In Thailand and Cambodia they have shown good agreement with
      observed epidemiological trends in surveillance populations and with changes in
      HIV transmission modes, AIDS cases, male:female ratios over time, and other
      external validation checks. By varying the input behaviours and STI trends, one
      can examine the impact of different prevention efforts on the future course of
      the epidemic. In conclusion, the AEM is a semi-empirical model, which has worked
      well in Asian settings. It provides a useful tool for policy and programme
      analysis in Asian countries.

PMID- 15249696
TI  - A global analysis of trends in the quality of HIV sero-surveillance.
AB  - OBJECTIVE: To examine the quality of HIV sero-surveillance systems in countries
      by 2002, as well as trends between 1995 and 2002. METHODS: The quality of
      countries' surveillance systems was scored for five years: 1995, 1997, 1999,
      2001, and 2002. Sero-surveillance data were compiled from the US Census Bureau's
      HIV/AIDS Surveillance Database, the EuroHIV database, and from countries'
      national HIV surveillance reports that were available to WHO/UNAIDS. The quality
      of systems was scored according to the level of the countries' epidemic. RESULTS:
      There has been a large variation in the quality of HIV surveillance systems
      across the 132 countries by type of the epidemic and over time from 1995 to 2002.
      Over the 1995-2002 period the number of countries with a fully implemented system
      decreased from 57 (43%) in 1995 to 48 (36%) in 2002. The proportion of countries
      with a fully implemented system was 58%, 34%, and 10% in countries with a
      generalised, concentrated, and low level epidemic, respectively. In the 53
      countries with generalised epidemics the number of countries with a fully
      implemented system increased from 24 (45%) in 2001 to 31 (58%) in 2002.
      CONCLUSION: Many countries still have poor functioning HIV surveillance systems
      and require urgent strengthening. Countries should monitor and evaluate their own
      HIV surveillance systems and examine whether the systems are appropriate and
      adequate.

PMID- 15249697
TI  - Uncertainty in estimates of HIV/AIDS: the estimation and application of
      plausibility bounds.
AB  - OBJECTIVES: To establish the accuracy of the country specific estimates of HIV
      prevalence, incidence, and AIDS mortality published every 2 years by UNAIDS and
      WHO. METHODS: We review sources of error in the data used to generate national
      HIV/AIDS and where possible estimate their statistical properties. We use
      numerical and approximate analytic methods to estimate the combined impact of
      these errors on HIV/AIDS estimates. Heuristic rules are then derived to produce
      plausible bounds about these estimates for countries with different types of
      epidemic and different qualities of surveillance system. RESULTS: Although 95%
      confidence intervals (CIs) can be estimated for some sources of error, the sizes
      of other sources of error must be based on expert judgment. We therefore produce
      plausible bounds about HIV/AIDS estimates rather than statistical CIs. The
      magnitude of these bounds depends on the stage of the epidemic and the quality
      and coverage of the sentinel HIV surveillance system. The bounds for adult
      estimates are narrower than those for children, and those for prevalence are
      narrower than those for new infections. CONCLUSIONS: This paper presents a first
      attempt at a rigorous description of the errors associated with estimation of
      global statistics of an infectious disease. The proposed methods work well in
      countries with generalised epidemics (>1% adult HIV prevalence) where the quality
      of surveillance is good. Although methods have also been derived for countries
      with low level or concentrated epidemics, more data on the biases in the
      estimation process are required.

PMID- 15249698
TI  - Hypothyroidism as a risk factor for cardiovascular disease.
AB  - The cardiovascular risk in patients with hypothyroidism is related to an
      increased risk of functional cardiovascular abnormalities and to an increased
      risk of atherosclerosis. The pattern of cardiovascular abnormalities is similar
      in subclinical and overt hypothyroidism, suggesting that a lesser degree of
      thyroid hormone deficiency may also affect the cardiovascular system. Hypothyroid
      patients, even those with subclinical hypothyroidism, have impaired endothelial
      function, normal/depressed systolic function, left ventricular diastolic
      dysfunction at rest, and systolic and diastolic dysfunction on effort, which may
      result in poor physical exercise capacity. There is also a tendency to increase
      diastolic blood pressure as a result of increased systemic vascular resistance.
      All these abnormalities regress with L-T4 replacement therapy. An increased risk
      for atherosclerosis is supported by autopsy and epidemiological studies in
      patients with thyroid hormone deficiency. The "traditional" risk factors are
      hypertension in conjunction with an atherogenic lipid profile; the latter is more
      often observed in patients with TSH >10 mU/L. More recently, C-reactive protein,
      homocysteine, increased arterial stiffness, endothelial dysfunction, and altered
      coagulation parameters have been recognized as risk factors for atherosclerosis
      in patients with thyroid hormone deficiency. This constellation of reversible
      cardiovascular abnormalities in patient with TSH levels <10 mU/L indicate that
      the benefits of treatment of mild thyroid failure with appropriate doses of L
      thyroxine outweigh the risk.

PMID- 15249699
TI  - Regulation of mRNA expression of matrix extracellular phosphoglycoprotein (MEPE)/
      osteoblast/osteocyte factor 45 (OF45) by fibroblast growth factor 2 in cultures
      of rat bone marrow-derived osteoblastic cells.
AB  - Matrix extracellular phosphoglycoprotein (MEPE)/ osteoblast/osteocyte factor 45
      (OF45) is a recently isolated RGD-containing matrix protein that acts as the
      tumor-derived phosphaturic factor in oncogenic hypophosphatemic osteomalacia. It
      is also highly expressed by osteoblasts and osteocytes. We examined the
      regulation of MEPE/OF45 mRNA expression in osteoblastic cells derived from high
      density cultures of primary rat bone marrow stromal cells incubated with
      dexamethasone, beta-glycerophosphate, and ascorbic acid. The level of MEPE/OF45
      mRNA in these cells was down-regulated by the addition of fibroblast growth
      factor 2 (FGF2) for 48 h. These effects were observed in a dose-dependent manner
      between 2 and 10 ng/mL. FGF2 also reduced the expression of osteocalcin mRNA in
      these cells. In contrast, bone sialoprotein mRNA expression was increased by
      FGF2, while alpha1(I) procollagen mRNA expression was not altered. Additionally,
      neither Runx2 and osterix mRNA expression nor cell proliferation were affected by
      the addition of FGF2 in these high-density cultures, indicating that regulation
      by FGF2 may not be dependent on these transcription factors or on the
      proliferation of cells. Experiments using actinomycin D indicated that FGF2
      decreased the stability of the MEPE/OF45 mRNA. Moreover, inhibition of a specific
      mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase
      kinase (MEK) by PD98059 blocked FGF2-regulated MEPE/OF45 expressions, indicating
      that this regulation requires the MAPK pathway. These results suggest that
      MEPE/OF45 gene is one of the targets of FGF2 and may play an important role
      during bone formation and calcification.

PMID- 15249700
TI  - Human alpha-subunit analogs act as partial agonists to the thyroid-stimulating
      hormone receptor: differential effects of free and yoked subunits.
AB  - The alpha-subunit is common to the heterodimeric glycoprotein hormones and has
      been highly conserved throughout vertebrate evolution. In an effort to determine
      if wild-type and engineered human alpha analogs can serve as agonists or
      antagonists to the human thyroid-stimulating hormone (TSH) receptor (TSHR), a
      potent alpha mutant, obtained by replacing four amino acid residues with lysine
      (alpha4K), was assayed and compared with the wild-type alpha-subunit. When added
      to CHO cells expressing TSHR, alpha4K, and to a very limited extent the fused
      homodimer, alpha4K-alpha4K, but not alpha, exhibited agonist activity as judged
      by cAMP production. When yoked to TSHR to yield fusion proteins, neither alpha,
      alpha4K, alpha-alpha, nor alpha4K-alpha4K activated TSHR, although yoked alpha4K
      and alpha4K-alpha4K were weak inhibitors of TSH binding to TSHR. The yoked
      subunit-receptor complexes were, however, functional as evidenced by increased
      cAMP production in cells co-expressing human TSHbeta and alpha-TSHR, alpha4K
      TSHR, alpha-alpha-TSHR, and alpha4K-alpha4K-TSHR. These results demonstrate that
      agonists to TSHR can be obtained with alpha-subunit analogs and suggest that
      rational protein engineering may lead to more potent alpha-based derivatives. The
      differences found between the experimental paradigms of adding free alpha analogs
      to TSHR and covalent attachment are attributed to con-formational constraints
      imposed by fusion of the alpha-subunit analog and receptor, and may suggest an
      important role for a free (C-terminal) alpha-carboxyl in the absence of the beta
      subunit.

PMID- 15249701
TI  - Comparison of cardiac contractile and intracellular Ca2+ response between
      estrogen and phytoestrogen alpha-zearalanol in ventricular myocytes.
AB  - While the benefit and risk of estrogen replacement therapy for cardiovascular
      disease remains controversial, women frequently choose alternatives to estrogen
      such as phytoestrogen for treatment of menopause even though medical indications
      for estrogens may exist. Phytoestrogens also possess distinct advantages over
      mammalian estrogens because their usage in men without feminizing side effects.
      Nevertheless, the cardiac contractile function of estrogen or phytoestrogen has
      not been clearly elucidated. The aim of the present study was to compare the
      effect of 17beta estradiol (E2) and phytoestrogen alpha-zearalanol (ZAL) on
      cardiac mechanical function and intracellular Ca2+ transients at cellular levels.
      Isolated ventricular myocytes from adult female rats were stimulated to contract
      at 0.5 Hz. Contractile properties were evaluated using an IonOptix MyoCam system
      including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening
      (TR90), and maximal velocity of shortening/relengthening (+/- dL/dt).
      Intracellular Ca2+ properties were evaluated as fura-2 fluorescent intensity
      change (DeltaFFI) and intracellular Ca2+ decay rate. Acute administration of E2
      (10(-9) - 10(-5) M) elicited a concentration-dependent increase in PS and
      DeltaFFI, with maximal augmentation of approx 35% and 25%, respectively. TPS,
      TR90, +/- dL/dt, resting intracellular Ca2+ level, and intracellular Ca2+ decay
      were unaffected by E2. None of the mechanical or intracellular Ca2+ indices
      tested was affected by phytoestrogen ZAL (10(-9) - 10(-5) M). Our results
      revealed a direct cardiac stimulatory action from E2 but not from phytoestrogen
      ZAL on ventricular contraction, likely mediated through enhanced intracellular
      Ca2+ release.

PMID- 15249702
TI  - L-prostaglandin D synthase expression and regulation in mouse testis and
      epididymis during sexual maturation and testosterone treatment after castration.
AB  - Lipocalin-type prostaglandin D synthase (L-PGDS) is highly expressed in the adult
      testis and epididymis of many mammals. The present study was to investigate L
      PGDS expression in mouse testis and epididymis during sexual maturation, and the
      effects of testosterone replacement on L-PGDS expression in epididymis by in situ
      hybridization and immunohistochemistry. Both L-PGDS mRNA and protein were highly
      expressed in the interstitial tissue of adult testis. L-PGDS mRNA was first
      detected on d 30 after birth and exhibited an abundant signal in adult caput and
      cauda epididymis. L-PGDS immunostaining was first observed on d 30 after birth.
      There was a strong level of L-PGDS immunostaining in adult epididymis. Castrated
      male mice were treated with either vehicle or testosterone propionate following 3
      d postcastration. L-PGDS expression steadily declined in a time-dependent fashion
      in control groups. No L-PGDS mRNA expression or immunostaining was detected in
      the controls for 12 d. When the castrated mice were treated with testosterone
      propionate for 5 or 12 d, L-PGDS expression was significantly increased in the
      whole epididymis. These data suggest that L-PGDS expression in mouse epididymis
      gradually declined in parallel to the declining concentration of endogenous
      androgen after castration and increased with the treatment of exogenous
      testosterone, indicating that L-PGDS expression in mouse epididymis was modulated
      by androgen levels. However, differential expression in different areas of the
      epididymis may also be influenced by factors derived from the testis.

PMID- 15249703
TI  - Hyperparathyroidism secondary to hypovitaminosis D in hypoalbuminemic is less
      intense than in normoalbuminemic patients: a prevalence study in medical
      inpatients in southern Brazil.
AB  - Hypovitaminosis D has been reported in tropical countries, but this hormone has
      seldom been studied in Brazil. Our purpose was to study the prevalence of
      hypovitaminosis D in patients hospitalized in internal medicine wards in Southern
      Brazil. Possible associated factors were studied. We studied 81 adult patients in
      early spring. Mean serum 25(OH)D was 12 +/- 8.57 ng/mL; hypovitaminosis D was
      severe (< 10 ng/mL) in 27 (33.3%) patients, and moderate (> or = 10 ng/mL and <
      20 ng/mL) in 36 (44.5%) patients. Clinical evaluation did not yield any data
      associated with hypovitaminosis D. Serum 25(OH)D levels of up to 20 ng/mL were
      associated with decreased mean serum total calcium (p = 0.001), ionized calcium
      (p = 0.01), and phosphorus (p = 0.044) levels, and increased mean serum PTH level
      (p = 0.001). In a multiple regression model, serum PTH level was independently
      affected by serum total calcium (p = 0.01), phosphorus (p = 0.009), and albumin
      (p = 0.009) levels. Hypovitaminosis D patients had lower mean serum albumin
      levels (p = 0.004), and serum 25(OH)D levels were directly correlated to serum
      albumin levels (p < 0.0001). Albumin influenced independently PTH response to
      hypovitaminosis D; normoalbuminemic hypovitaminosis D patients had higher mean
      serum PTH than hypoalbuminemic patients. CONCLUSION: Hypovitaminosis D prevalence
      was very high in medical inpatients in Southern Brazil, in early spring.
      Nevertheless, secondary hyperparathyroidism was less intense in hypoalbuminemic
      hypovitaminosis D patients suggesting that in these patients free serum 25(OH)D
      was closer to normal.

PMID- 15249704
TI  - Clinical characteristics of eight patients with congenital nephrogenic diabetes
      insipidus.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is characterized by the
      insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge
      of this disease is based largely on case reports. For this study, we investigated
      the clinical findings of eight patients in terms of age at onset, age at
      diagnosis, main complaint, results of physical examination, the diagnosis, the
      effect of treatment, kidney function, and presence or absence of gene defects.
      The main complaints of all eight cases at initial examination were unknown fever,
      failure to thrive, and short stature. Polyuria and polydipsia are not always the
      chief complaints with congenital NDI. In one case, diabetes insipidus could be
      diagnosed based only on the results of a 5% hypertonic saline test. In six cases,
      we found abnormalities in the V2 receptor gene. Initially, trichlormethiazide
      therapy was shown to have a significant effect on polyuria; however, this effect
      decreased over time. In one patient with partial NDI, the addition of
      trichlormethiazide twice a day to 1-desamino-8-D-arginine vasopressin increased
      urine osmolality in the morning and caused nocturia to disappear. Results of
      99mTc-diethylenetriamine pentaacetic acid kidney scintigraphy revealed a slight
      decrease in glomerular filtration rate in three patients. No patient experienced
      serious renal dysfunction.

PMID- 15249706
TI  - Immediate and delayed effects of D-fructose upon insulin, somatostatin, and
      glucagon release by the perfused rat pancreas.
AB  - Novel information was recently provided concerning the reciprocal effects of D
      glucose and D-fructose upon their respective metabolism in rat pancreatic islets.
      In the light of such findings, this study aims at comparing the effects of D
      glucose and D-fructose on insulin, somatostatin, and glucagon release from the
      isolated perfused rat pancreas. A rise in D-glucose concentration from 3.3 to 5.0
      or 7.3 mM or the administration of D-fructose (17 and 40 mM) in the presence of
      3.3 mM D-glucose stimulated insulin release in a concentration-related manner,
      but failed to affect somatostatin output. The secretion of glucagon was decreased
      in all cases. The secretory response to L-arginine (5 mM), 25 min after restoring
      the basal concentration of D-glucose, was more markedly affected, in terms of
      potentiation of insulin and somatostatin release and reduction of glucagon
      output, after prior administration of D-fructose than after a prior increase in D
      glucose concentration. These findings argue against any major role for a
      paracrine regulation of hormonal release and, instead, are consistent with a
      causal link between metabolic and secretory events in the islet cells.
      Nevertheless, the present results emphasize differences in the response of
      distinct pancreatic endocrine cell types to the same or distinct hexoses.

PMID- 15249705
TI  - Effects of nitric oxide on aldosterone synthesis and nitric oxide synthase
      activity in glomerulosa cells from bovine adrenal gland.
AB  - This study investigated the effects of two NO-releasing agents,
      diethylenetriamine-NO (deta-NO) and sodium nitroprusside (SNP), on basal, ACTH-,
      and angiotensin II (AngII)-stimulated aldosterone production in glomerulosa cells
      from bovine adrenal gland. NO donors inhibited basal and ACTH- or AngII
      stimulated aldosterone synthesis in a concentration-dependent manner. Deta-NO and
      SNP also provoked a concentration-dependent stimulation of cGMP production.
      However, cGMP was not responsible for the inhibition of aldosterone secretion,
      because a cGMP analog did not reproduce the inhibitory effect. Moreover, soluble
      guanylyl cyclase or protein kinase G inhibitors did not revert the inhibitory
      effect of NO on aldosterone production. NO donors did not modify ACTH-stimulated
      cAMP production or AngII-stimulated PLC activity stimulation, but inhibited 22[R]
      hydroxycholesterol- or pregnenolone-stimulated aldosteronogenesis. NO can be
      synthesized in bovine glomerulosa cells because nitrite production was determined
      and characterization of NOS activity was also performed. Nitrite accumulation was
      not modified in the presence of ACTH, AngII, or other factors used to induce
      iNOS. NOS activity that showed a Michaelis-Menten kinetic was NADPH- and calcium
      dependent and was inhibited by two competitive inhibitors, L-NAME and L-NMMA.
      These results show that NO inhibits aldosterone production in glomerulosa cells
      acting on P450scc and other P450-dependent steroidogenic enzymes, and these cells
      display NOS activity suggesting that NO can be produced by constitutive NOS
      isozymes.

PMID- 15249707
TI  - Effects of thioacetamide on pancreatic islet B-cell function.
AB  - Thioacetamide (0.01-1.3 mM) fails to exert any significant immediate effect upon
      insulin release from rat isolated islets. However, when administered (4
      micromol/g body wt) intraperitoneally 24 h before sacrifice, it reduced food
      intake and body weight and affected the secretory response of isolated islets to
      several secretagogues, despite unaltered insulin content of such islets. This
      coincided with a decrease in D-[U-14C]glucose oxidation, total islet calcium
      content and the ionized calcium content of secretory granules in islet B-cells,
      and changes in both 133Ba and 45Ca net uptake. Likewise, in islets prepared from
      thioacetamide-injected rats and prelabeled with 45Ca before perifusion, the
      cationic and insulin secretory responses to D-glucose or gliclazide, but not to
      the association of Ba2+ and theophylline in the absence of extracellular Ca2+,
      often differed from that otherwise found in islets prepared from control rats.
      These findings are interpreted as indicative of an impaired capacity of Ca2+
      sequestration by intracellular organelles in the islet B-cells of thioacetamide
      treated rats.

PMID- 15249709
TI  - Retroperitoneal malignant fibrous histiocytoma mimicking pheochromocytoma.
AB  - We report the case of a 52-yr-old man with a mass in the area of the left
      adrenal. The clinical features, MIBG uptake, and elevated urinary dopamine levels
      suggested the diagnosis of pheochromocytoma. He presented with unstable
      hypertension, tachycardia, weight loss, and the "inflammatory syndrome" (fever,
      leukocytosis, and high sedimentation rate). Clinical findings, preoperative
      radiographic (sonography, CT scan, [131I]MIBG scintigraphy), and endocrine
      evaluations (elevated 24-h urinary dopamine) were suggestive of a dopamine
      secreting adrenal tumor. The mass was resected and on histologic examination
      showed the characteristic features of a malignant fibrous histiocytoma (MFH). The
      tumor cells were immunopositive for neuron-specific enolase (NSE), vimentin, CD
      68, S-100, desmin, and immunonegative for chromogranin A, synaptophysin,
      neurofilament protein, and low-molecular-weight keratin, indicating that this
      tumor was not able to synthesize catecholamines. The prolonged retention of the
      tracer (MIBG) was interpreted as a consequence of obstructive hydronephrosis,
      while elevated urinary dopamine levels were assumed to be due to compression of
      the renal vessels by the large retroperitoneal mass.

PMID- 15249708
TI  - Ghrelin and other glucoregulatory hormone responses to eccentric and concentric
      muscle contractions.
AB  - OBJECTIVE: Heavy resistance exercise increases growth hormone (GH) and blood
      glucose levels. Ghrelin is an endogenous ligand for the GH secretagory receptor
      that stimulates growth hormone release. Circulating ghrelin levels are suppressed
      by insulin and glucose. The study was conducted to determine effects of
      concentric (CON) and eccentric (ECC) muscle actions at the same absolute workload
      on circulating ghrelin and glucose as well as related glucoregulatory peptides.
      METHODS: Ten-RM loads for bench press, leg extension, military press, and leg
      curl were obtained from nine males, mean age 25. +/- 1.2 yr and body fat 17.2 +/-
      1.6%. Subjects then completed two experimental trials of either CON or ECC
      contractions at the same absolute workload. Subjects performed four sets of 12
      repetitions for each exercise at 80% of a 10-RM with 90 s rest periods. A pulley
      system or steel levers were positioned on each machine to raise or lower the
      weight so only CON or ECC contractions were performed. Pre-, post-, and 15-min
      post-exercise blood samples were collected. RESULTS: Ghrelin did not increase in
      response to either muscle action and actually declined during the CON trial.
      Glucose and insulin increased regardless of the form of muscle action, but amylin
      and C-peptide did not change. CONCLUSIONS: Data indicate that ghrelin does not
      contribute to moderate resistance exercise-induced increases in growth hormone,
      whether from CON or ECC muscle actions. Results suggest that with a moderate
      loading protocol both CON and ECC muscle actions performed at the same absolute
      workload elevate glucose and insulin concentrations, but are not related to post
      CON exercise ghrelin suppression.

PMID- 15249710
TI  - Hereditary pancreatic endocrine tumours.
AB  - The two main types of hereditary pancreatic neuroendocrine tumours are found in
      multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL),
      but also in the rarer disorders of neurofibromatosis type 1 and tuberous
      sclerosis. This review considers the major advances that have been made in
      genetic diagnosis, tumour localization, medical and surgical treatment and
      palliation with systemic chemotherapy and radionuclides. With the exception of
      the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can
      be treated medically. The role of surgery however remains controversial ranging
      from no intervention (except enucleation for insulinoma), intervening for tumours
      diagnosed only by biochemical criteria, intervening in those tumours only
      detected radiologically (1-2 cm in diameter) or intervening only if the tumour
      diameter is > 3 cm in diameter. The extent of surgery is also controversial,
      although radical lymphadenectomy is generally recommended. Pancreatic tumours
      associated with VHL are usually non-functioning and tumours of at least 2 cm in
      diameter should be resected. Practice guidelines recommend that screening in
      patients with MEN-1 should commence at the age of 5 years for insulinoma and at
      the age of 20 years for other pancreatic neuroendocrine tumours and variously at
      10-20 years of age for pancreatic tumours in patients with VHL. The evidence is
      increasing that the life span of patients may be significantly improved with
      surgical intervention, mandating the widespread use of tumour surveillance and
      multidisciplinary team management.

PMID- 15249711
TI  - Staging of pancreatic head adenocarcinoma with spiral CT and endoscopic
      ultrasonography: an indirect evaluation of the usefulness of laparoscopy.
AB  - BACKGROUND: The interest of laparoscopy in the preoperative staging of pancreatic
      head adenocarcinoma before curative pancreaticoduodenectomy is a matter of
      controversy and depends on the accuracy of preoperative imaging techniques. AIM:
      To assess the potential value of laparoscopy when a standardised and optimal
      preoperative staging is performed, including spiral computed tomography (CT) and
      endoscopic ultrasonography (EUS). METHODS: All consecutive patients operated on
      with a view to curative pancreaticoduodenectomy for pancreatic head or ampullary
      adenocarcinoma in our centre from January 1998 to August 2000 were
      retrospectively studied. All of them had preoperative spiral CT and EUS. Tumour
      resectability was considered as highly probable (HP) or uncertain (U) according
      to well-defined criteria. Operative records of patients were reviewed to
      indirectly assess the effective resectability rate and the criteria responsible
      for unresectability and which of them would have been identified by laparoscopy
      if initially performed. RESULTS: 69 consecutive patients were studied.
      Resectability was HP (n = 56) or U (n = 13) after preoperative staging. Curative
      pancreatoduodenectomy was performed in 53 patients (77%) (48 HP, 5 U). Positive
      predictive value of preoperative imaging for highly probable resectability was
      86% (48/56). Among the 16 unresectable tumours (8 HP, 8 U), the cause of non
      resection would have been found at laparoscopy in 9 patients (56%) (6 HP, 3 U).
      Finally, if initially performed, laparoscopy would have avoided laparotomy in
      9/69 patients (13%) (6/56 HP (11%); 3/13 U (23%)). CONCLUSIONS: With accurate
      preoperative staging using spiral CT and EUS, laparoscopy would detect tumours
      which were unresectable in 13% of patients with pancreatic head cancer.
      Laparoscopy remains useful in selected patients, such as those with preoperative
      uncertain resectability, in whom it can prevent unnecessary laparotomy in one
      fourth of patients.

PMID- 15249712
TI  - High-dose chemotherapy in childhood brain tumors.
AB  - Early attempts to use high-dose chemotherapy technology in order to improve the
      effect of nitrosourea on high-grade gliomas resulted in minimal benefit as well
      as in severe toxicity. Since then, other drugs have been applied in conjunction
      with either autologous bone marrow or peripheral blood stem cells, including
      thiotepa, etoposide, melphalan, cyclophosphamide, and busulfan. The data suggest
      benefit in recurrent primitive neuroectodermal tumors (PNET), in newly diagnosed
      young children with PNET and possibly in young children with newly diagnosed
      ependymoma, as a strategy not only to improve tumor-free survival but also to
      avoid exposure of the young brain to irradiation. In other tumors such as
      recurrent ependymoma and newly diagnosed or recurrent brain stem glioma, high
      dose chemotherapy remains ineffective. New protocols under evaluation include new
      agents, multiple cycles of high-dose chemotherapy and allogeneic transplantation
      as immunotherapeutic approach.

PMID- 15249713
TI  - Current and future trials of the EORTC brain tumor group.
AB  - The EORTC Brain Tumor Group (BTG) is dedicated to clinical research of neoplasms
      of the brain. In the past years the BTG has carried out phase II and phase III
      trials on glial tumors, brain metastases and primary CNS lymphomas. Future
      studies will investigate novel drugs in combination with chemo-radiotherapy in
      glioblastoma multiforme, radiotherapy in meningioma, and chemotherapy in
      medulloblastoma. The BTG will also start a new phase III trial on newly diagnosed
      low-grade glioma comparing radiotherapy to temozolomide. In all our trials
      translational research is getting more and more important, often this is one of
      the most important ways to get useful conclusions from clinical trials. The wide
      recognition of the importance of translational research for clinical trials and
      in particular with targeted therapies implies that this type of research will
      become a mandatory element in many of our future trials.

PMID- 15249714
TI  - Diagnosis and treatment of paraneoplastic neurological disorders.
AB  - In about two thirds of cases, patients with paraneoplastic neurological disorders
      present to the neurologist without a known tumor. Due to the ongoing immune
      response, this tumor tends to stay biologically relatively benign, and therefore
      difficult to diagnose. In patients with a known tumor, the neurological symptoms
      often precede a tumor recurrence. In both scenarios, anti-neuronal antibodies are
      an invaluable diagnostic help to the clinician, and may be supplemented by other
      diagnostic tests such as MRI, CSF, and electrophysiology. Tumor therapy remains
      the mainstay of therapeutic options, although early immune therapy must be
      started in parallel. It is hoped that the recent fundamental advances in
      understanding the autoimmune pathology of these disorders, especially the role of
      cytotoxic T cells, will eventually lead to more effective treatment options.

PMID- 15249715
TI  - Brain edema in neurooncology: radiological assessment and management.
AB  - Vasogenic brain edema is a common diagnostic and management problem in brain
      tumor patients. Molecular mechanisms play a role in the pathophysiology,
      including abnormalities of tumor endothelium, vascular endothelial growth factor
      and leukotriene synthase. Edema diagnosis is facilitated by the development of
      neuroradiological imaging techniques, with diffusion-weighted imaging (DW-MRI)
      differentiating tumor grades or abscesses and tumors, and diffusion tensor
      imaging representing an advanced technique to potentially differentiate malignant
      glioma from metastasis or facilitate preoperative planning. Edema is a prognostic
      factor for meningioma and metastases but not for glioma. Therapy includes,
      amongst others, tumor-directed measures such as debulking surgery, radio- and
      chemotherapy. However, local therapeutic approaches might also induce or
      exacerbate edema formation. Peritumoral edema can usually be managed with
      corticosteroids. However, patients on corticosteroids are at greater risk of
      metabolic changes, Pneumocystis carinii pneumonia, and thromboembolism. More
      recently, inhibitors of cyclooxygenase-2 as well as boswellic acids have been
      explored as antiedema agents in patients with brain tumors.

PMID- 15249716
TI  - Gemtuzumab ozogamicin (Mylotarg) in children with refractory or relapsed acute
      myeloid leukemia.
AB  - BACKGROUND: Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the
      CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted
      treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed
      and refractory AML. PATIENTS AND METHOD: We report 12 children with multiple
      relapsed or refractory AML receiving GO as compassionate use. 11 children had
      initially been treated according to the AML-BFM 93 or 98 protocol, 1 girl
      received relapse treatment (liposomal daunorubicin/FLAG) due to secondary AML.
      After relapse, 10 children received an intensive relapse therapy (AML-BFM 97 or
      international AML-Relapse Study 2001/01). 2 of them had been transplanted in
      first or second CR before GO therapy. RESULTS: 5 of 12 children responded to
      treatment with blast reduction to below 5%, but no child achieved CR after GO.
      Time until reoccurrence of blasts in almost all children with GO response was 3-8
      months. In 5 children stem cell transplantation (SCT) was performed after GO
      therapy. 4 of them suffered from further progression of AML, 1 boy is in second
      remission with a follow-up of 8 months. 2 children had severe side effects. An
      anaphylactic reaction with severe hypotension was managed by catecholamine
      support and intensive care. In 1 girl, who relapsed after SCT in first remission,
      a veno-occlusive disease of the liver occurred, but could be treated successfully
      with defibrotide. CONCLUSION: GO therapy can induce blast reduction in children
      who have no further conventional treatment options. Frequency and severity of
      adverse events are limited, and therapy seems to be feasible for children with a
      sufficient general condition. Controlled studies are necessary to learn more
      about efficacy and side effects, especially implications for further therapy.

PMID- 15249717
TI  - Second autologous transplantation for multiple myeloma patients relapsing after
      the first autograft -- a pilot study for the evaluation of experimental
      maintenance therapies. Report of the prospective non-randomized pilot study of
      the Czech Myeloma Group.
AB  - BACKGROUND: High-dose chemotherapy followed by autologous stem cell
      transplantation (AT) is accepted as first-line therapy for patients with multiple
      myeloma (MM), with very good tolerance and low mortality (2-3%). STUDY DESIGN: We
      tested repeated transplantation with different experimental maintenance therapies
      in patients with MM relapsing/progressing after first AT. Results were compared
      using intra-individual analyses, therefore inter-individual differences are
      excluded (T2 model). PATIENTS AND METHODS: Between January 1997 and January 2003,
      32 patients with relapsing/progressing MM after first AT were included in the
      pilot study, median follow-up was 75.2 months. They received the following
      experimental therapies: IL-2-activated PBSC (10 pts), pamidronate (4 pts),
      thalidomide (15 pts), consolidation chemotherapy CED (3 pts). RESULTS:
      Sensitivity to C-VAD reinduction chemotherapy (4 cycles) was 50%, response to the
      second AT compared to the first was better in 7, the same in 16 and worse in 9
      patients. Toxicity of the first and second transplantation was similar and
      usually did not exceed grade II (SWOG). Transplant-related mortality was 3%
      (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7
      have achieved prolongation of EFS II versus EFS I. In the whole group median EFS
      I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS)
      was 79.1 months; 20/32 patients were alive at the time of analysis. CONCLUSIONS:
      Repeated AT is a feasible and successful strategy in treatment of relapsing MM;
      response to second AT and toxicity were acceptable and similar to the first AT in
      our assessment.

PMID- 15249718
TI  - Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as
      first-line treatment of small cell lung cancer.
AB  - BACKGROUND: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus
      cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This
      study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of
      escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with
      small cell lung cancer. PATIENTS AND METHODS: Patients with extensive small cell
      lung cancer received 50 mg/m(2) irinotecan on day 1, 8, and 15. Dose escalation
      of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg x min/ml and
      was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose
      escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia
      lasting for > or =7 days or thrombopenia or non-hematologic toxicity > or = grade
      III occurred, treatment was continued in the next dose level. RESULTS: 16
      patients were treated. DLT was reached in dose level 2 with 2 grade IV
      neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further
      investigated at dose level 1 in a total of 10 patients, which revealed 2 grade
      III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a
      partial response, 3 had disease stabilization and 2 progressed. CONCLUSION: Dose
      level 1 was found to be MTD, this dose is currently compared to the combination
      of etoposide plus carboplatin within a randomised phase II/III trial.

PMID- 15249719
TI  - Role of F18-FDG PET for monitoring of radiochemotherapy -- estimation of
      detectable number of tumour cells.
AB  - BACKGROUND: FDG-PET has been proven to be useful for the diagnosis of pancreatic
      cancer. However, no quantitative data exist concerning its sensitivity for
      treatment monitoring or early diagnosis. CASE REPORT: We report on a 61-year-old
      patient with locally advanced cancer of the pancreas head who received sequential
      radiochemotherapy including gemcitabine and 5-FU/FA. Under this regimen, MR and
      CT showed a partial remission with a residual mass which seemed to allow surgical
      treatment for this patient. A pre-operative FDG-PETScan displayed a count rate
      close to the detection limit of vital residual tumour. An R0 resection was
      performed successfully. However, histopathology revealed residual tumour at the
      core of the resected mass that had gone undetected by all imaging modalities.
      CONCLUSION: The number of vital tumour cells within this specimen was estimated
      to be 10(6)-10(7). The detection threshold for FDG-PET in pancreatic carcinoma
      appears to be within this range.

PMID- 15249720
TI  - Synchronous squamous cell carcinoma of the stomach, the lung and the skin.
AB  - BACKGROUND: The incidence of multiple primary cancers is reported to be 0.3-4.3%.
      CASE REPORT: A 70-year-old man was admitted to the hospital because of fatigue,
      weight loss, epigastric pain with melena. A biopsy taken from a tumoral lesion in
      the gastric corpus revealed squamous cell carcinoma. A nodular lesion was also
      detected on the nasal columella and biopsy from this lesion also showed squamous
      cell carcinoma. Computed tomography performed as a part of metastatic work-up
      revealed a lesion in the left pulmonary lower lobe. Bronchoscopic biopsy from
      this lesion also demonstrated squamous cell carcinoma. RESULTS: We report a case
      with synchronous squamous cell carcinoma of the lung, skin and stomach and
      discuss the multiple synchronous occurrence of carcinoma with the same
      histopathology in different sites with a review of the literature.

PMID- 15249721
TI  - Multimodal treatment of hepatocellular carcinoma (HCC).
AB  - Screening of patients at risk for hepatocellular carcinomas (HCC) and preventive
      virustatic therapy are the first steps in a multimodal treatment concept, because
      delayed detection leads to a poor prognosis with median survival of <10 months.
      Surgical resection of HCC is still the treatment of choice in patients with good
      residual liver function, however, recurrence-free 5-year survival after curative
      resection is low (33%). In patients with cirrhosis, only 25% of HCC are
      resectable, limited by low hepatic functional reserve. HCC in patients with non
      cirrhotic livers are the domain of extended resections. In newer reports,
      transplantation in patients with cirrhosis is rated more positively when
      restricted to patients with solitary nodules <5 cm or up to 3 tumors <3 cm. A new
      option in HCC therapy are the local methods for tumor ablation, preferably
      radiofrequency ablation (RFA), especially in patients with limited liver
      function, non-resectable or multifocal tumors. A new horizon is opened combining
      these options and multimodal approaches with transarterial chemoembolisation
      (TACE). This trend to multimodal approaches promises a yet unknown improvement in
      the prognosis of patients with HCC. Controlled randomized studies comparing and
      validating the different methods and defining combined treatments according to
      liver function and tumor stage are eagerly awaited.

PMID- 15249722
TI  - Magnetic resonance spectroscopy in clinical oncology.
AB  - The combination of magnetic resonance spectroscopy (MRS) and imaging (MRI) has
      led to mapping metabolites from normal and neoplastic tissue within the time
      limits of a routine study. MRSI (magnetic resonance spectroscopy imaging) detects
      metabolites that contain protons, phosphorus, fluorine, or other nuclei. The
      uniqueness of the information available in vivo and in a non-invasive manner
      encouraged radiologists and oncologists to apply MRSI in research and clinical
      practice. Both (1)H- and (31)P-MRS have revealed significant disturbances in
      amino acids, lipids, and phosphorus-containing metabolites within tumors.
      Phosphocreatine is often diminished in neoplasms compared to their primary host
      or surrounding tissues. However, the reduction of the compound does not appear to
      be closely correlated to the degree of malignancy. Moreover, abnormalities in
      (31)P spectra from neoplasms are shared by other disorders. Changes in high
      energy phosphate levels almost invariably occur with radio- and chemotherapy of
      tumors. The spectroscopic alterations are often seen before any variations in
      tumor size and shape can be detected. However, opposite responses can be
      associated with the same clinical outcome. (1)H-MRS has been successfully used to
      quantify the extent of neuronal cell loss imposed on the brain during
      radiotherapy. Recently, MRSI was successfully integrated into radiotherapy
      planning in prostate cancer patients. (19)F-MRS opens access to artificially
      induced fluorocompounds such as 5-fluorouracil and its metabolites.

PMID- 15249723
TI  - Is there a role for chemosensitivity tests in head and neck cancer?
AB  - Despite many advances in predictive testing of human malignancies, we are far
      from using it routinely in clinical practice. Investigating the responsiveness of
      solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for
      head and neck cancer, chemosensitivity testing is an increasingly attractive
      option, since chemotherapy has proven to have curative potential in the therapy
      of head and neck cancer, in particular in combination with radiation. The
      significant need for predictive methods to identify patients responsive to
      therapy, first of all in organ preservation programs, which is an alternative to
      first-line surgery, had recently renewed the discussion on a possible role of
      chemosensitivity testing in head and neck cancer. In this review, we discuss the
      current state of chemosensitivity testing in head and neck cancer. Recent
      methodological developments, in particular elimination of photochemical artifacts
      and inclusion of stromal cell response studies, may soon augment the value of ex
      vivo chemosensitivity testing for the management of head and neck cancer.

PMID- 15249724
TI  - Risks of guidelines in medicine.

PMID- 15249725
TI  - IL-2 and IL-10 production by human CD4+T cells is differentially regulated by
      p38: mode of stimulation-dependent regulation of IL-2.
AB  - Antigenic stimulation of T cells initiates a complex series of intracellular
      signaling pathways that target and activate different cytokine genes. The
      participation of mitogen-activated protein kinases (MAPKs) in these processes has
      not been studied thoroughly and in some instances conflicting results have been
      reported. Here we have examined the role of p38 MAPK on IL-2 and IL-10 production
      following activation of human CD4+ T cells or of the leukemic cell line Hut-78,
      with either plate-bound anti-CD3 in the presence or absence of soluble anti-CD28
      (plCD3, plCD3/sCD28), or with cross-linked anti-CD3 and anti-CD28 (crsCD3+CD28),
      or with PMA plus ionomycin. Pharmacological inhibition of the p38 pathway with
      either SB203580, SB202190, or SKF86002 strongly downregulated IL-10 production by
      T cells stimulated with any of the above treatments. In contrast the effect of
      p38 inhibition on IL-2 was stimulus dependent. Thus, p38 inhibition strongly
      upregulated IL-2 production (up to 10-fold) in the plCD3- and plCD3/sCD28
      stimulated cultures while it had minimal or no effect in the other two
      stimulation protocols. Intracellular and mRNA levels of IL-2 and IL-10 were also
      upregulated and downregulated, respectively, by p38 inhibitors in the plCD3/sCD28
      stimulated CD4+ T cells. Also, the induction of IL-2 and the parallel suppression
      of IL-10 by p38 inhibitors were independent of the balance between these two
      cytokines, as demonstrated by the addition of exogenous IL-10 or blocking anti-IL
      10 antibody in CD4+ and Hut-78 cell cultures. These results show that p38 acts as
      a molecular switch that changes the balance between IL-2 and IL-10. This is
      especially important considering the opposing role of these cytokines in
      peripheral immune tolerance.

PMID- 15249726
TI  - Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto's
      thyroiditis (Th1) and Graves' disease (Th2).
AB  - OBJECTIVES: The aim of this study was to document the pattern of immune response,
      assessed by the measurement of both Th1 and Th2 serum cytokines, in patients
      suffering from autoimmune thyroid disease and toxic nodular goiter. METHODS: Both
      Th1 and Th2 serum cytokine levels were assayed in patients suffering from Graves'
      disease (GD, n = 25), Hashimoto's thyroiditis (HT, n = 21), and toxic nodular
      goiter (TNG, n = 7) and compared with corresponding levels of 25 healthy
      controls. Serum concentrations of IL-2, IL-1 beta, INF-gamma, TNF-alpha, IL-12,
      IL-15, IL-10, IL-18, IL-4 and IL-5 were assayed in fasting serum samples.
      RESULTS: It was found that patients with HT had higher IL-2 serum levels (12.16
      +/- 0.66 pg/ml) compared to patients with TNG (9.25 +/- 0.84 pg/ml), GD (7.86 +/-
      0.30 pg/ml) and controls (7.36 +/- 0.45 pg/ml; p = 0.0001), higher INF-gamma
      levels (7.60 +/- 0.33 pg/ml) compared to patients with TNG (5.77 +/- 0.55 pg/ml),
      GD (5.74 +/- 0.24 pg/ml) and controls (5.09 +/- 0.27 pg/ml; p = 0.0009), higher
      IL-12 levels (3.57 +/- 0.19 pg/ml) compared to patients with TNG (2.57 +/- 0.21
      pg/ml), GD (2.48 +/- 0.13 pg/ml) and controls (2.59 +/- 0.23 pg/ml; p = 0.004),
      and higher IL-18 levels (27.52 +/- 1.75 pg/ml) compared to patients with TNG
      (18.71 +/- 2.24 pg/ml), GD (15.44 +/- 1.39 pg/ml) and controls (15.16 +/- 1.62
      pg/ml; p = 0.0002). In contrast, patients with GD had higher serum levels of IL-4
      (4.11 +/- 0.33 pg/ml) compared to patients with HT (3.0 +/- 0.16; p = 0.02) and
      higher IL-5 levels (4.22 +/- 0.30 pg/ml) compared to patients with TNG (3.21 +/-
      0.58 pg/ml), HT (2.75 +/- 0.16 pg/ml) and controls (2.0 +/- 0.19 pg/ml; p =
      0.0001). Patients had lower IL-1 beta serum levels (TNG 2.45 +/- 0.20, HT 2.52 +/
      0.14, GD 2.68 +/- 0.12 pg/ml) compared to controls (3.6 +/- 0.20 pg/ml; p =
      0.008). CONCLUSIONS: The above findings suggest that a Th1 pattern of immune
      response characteristic of cellular immunity is dominant in HT, whereas the
      predominance of Th2 cytokines in GD indicates a humoral pattern of immune
      reaction.

PMID- 15249727
TI  - Adrenergic modulation of survival and cellular immune functions during
      polymicrobial sepsis.
AB  - OBJECTIVE: An immunomodulatory effect of epinephrine has been reported that is
      supposed to be mediated via beta-adrenergic receptors. The effect of epinephrine
      and/or beta-adrenergic blockade on cellular immune functions during systemic
      inflammation has not yet been investigated. METHODS: Male NMRI mice were treated
      with either an infusion of epinephrine (0.05 mg/kg/h i.p.), administration of the
      nonselective beta-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a
      combination of epinephrine and propranolol after induction of a polymicrobial
      sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and
      cellular immune functions (splenocyte proliferation, splenocyte apoptosis and
      cytokine release, distribution of leukocyte subsets) were determined. RESULTS:
      Infusion of epinephrine did not affect lethality of septic mice but induced
      alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release
      and was associated with profound changes of circulating immune cell
      subpopulations. Treatment with propranolol augmented the epinephrine-induced
      increase of splenocyte apoptosis, did not affect the decrease of splenocyte
      proliferation and IL-2 release, augmented the release of IL-6 and antagonized the
      mobilization of natural killer cells observed in epinephrine-treated animals.
      Furthermore, these immunologic alterations were accompanied by a significant
      increase of sepsis-induced mortality. Coadministration of propranolol and
      epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and
      IL-6 release and was associated with the highest mortality of septic mice.
      CONCLUSION: Epinephrine infusion modulated cellular immune functions during
      systemic inflammation without an impact on survival. A pharmacologic beta
      adrenergic blockade partly augmented the epinephrine-induced immune alterations
      and was associated with a pronounced increase of mortality. This effect was
      further augmented by a combination of epinephrine infusion and beta-adrenergic
      blockade. These data indicate that adrenergic mechanisms modulate cellular immune
      functions and survival during sepsis, with these effects being mediated via alpha
      and beta-adrenergic pathways.

PMID- 15249728
TI  - Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells-
      redundancy or specificity of neuroimmunoendocrine modulators?
AB  - OBJECTIVE: This comparative in vitro study examined the effects of all known
      gp130 cytokines on murine corticotroph AtT-20 cell function. METHODS: Cytokines
      were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine
      phosphorylation of the signal transducer and activator of transcription (STAT)3
      and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter
      activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and
      adrenocorticotropic hormone (ACTH) secretion were determined. RESULTS: Leukemia
      inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1
      (LIFR/gp130 ligands), as well as ciliary neurotrophic factor (CNTF) and novel
      neurotrophin-1/B-cell stimulating factor-3 (CNTFR alpha/LIFR/gp130 ligands) are
      potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6
      (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct
      effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect.
      CONCLUSION: (i) CNTFR complex ligands are potent stimuli of corticotroph
      function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively
      weak direct stimuli of corticotroph function; (iii) differential effects of human
      and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR
      type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto
      unknown ability to stimulate corticotroph function, and (v) despite redundant
      immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells
      are preferably activated through the LIFR and CNTFR complexes.

PMID- 15249729
TI  - Effects of neurointermediate pituitary lobectomy on humoral and cell-mediated
      immune responses in the rat.
AB  - OBJECTIVE: Chronic stress is characterized by an increased activity of the
      hypothalamic-pituitary-adrenocortical axis and decreased humoral and cell
      mediated immune responses. In the rat, corticosterone is the principal natural
      immune suppressor. Neurointermediate pituitary lobectomy (NIL) in rats induces
      diabetes insipidus and protracted increases in basal adrenocorticotropin and
      corticosterone plasma levels, a situation that resembles chronic stress. In this
      paper, we evaluated the effects of NIL on humoral (hemagglutinin titers and
      footpad swelling to sheep red blood cells--SRBC) and cell-mediated immune
      responses (contact hypersensitivity to dinitrochlorobenzene). METHODS: The
      studies were conducted on NIL Wistar rats (body weight 150-200 g) 3 weeks after
      surgery. For comparisons, nonoperated control rats were used. RESULTS: NIL
      resulted in an increased water intake. Body weight gain and adrenal, thymus, and
      spleen weights were within the range of nonoperated controls. Eight days after
      SRBC immunizations a second SRBC injection into the footpad resulted in a
      decreased swelling response in NIL rats. The hemagglutinin titers were also
      reduced in the NIL rats. CONCLUSIONS: These results indicate that: (1) NIL
      reduces humoral immune responses and decreases the cell-mediated immune response;
      (2) the immune alterations are most likely due to the increased activity of the
      hypothalamic-pituitary-adrenocortical axis induced by NIL, and (3) NIL animals
      constitute a valuable paradigm to study hypothalamic-pituitary-immune
      interactions.

PMID- 15249730
TI  - Corticosterone changes in response to stressors, acute and protracted actions of
      tumor necrosis factor-alpha, and lipopolysaccharide treatments in mice lacking
      the tumor necrosis factor-alpha p55 receptor gene.
AB  - Systemic administration of the proinflammatory cytokine, tumor necrosis factor
      alpha (TNF-alpha), has acute as well as sensitizing effects on behavioral and
      neurochemical functioning. OBJECTIVES: As many of the central consequences of TNF
      alpha are mediated by its p55 receptor, the present investigation determined the
      role of this receptor on the plasma corticosterone increase associated with the
      acute TNF-alpha treatment and the sensitized response evident upon reexposure to
      the cytokine. Moreover, the role of p55 in the provocation of corticosterone
      release engendered by lipopolysaccharide (LPS) and psychogenic stressors (noise
      or restraint) was also determined. METHODS: Plasma corticosterone levels were
      determined in wild-type and p55-deficient mice that received systemic treatments
      with TNF-alpha and LPS, as well as exposure to auditory and restraint stressors.
      RESULTS: Mice deficient for p55 displayed a greatly attenuated plasma
      corticosterone response to TNF-alpha irrespective of whether they had been
      previously exposed to the cytokine. In contrast, p55 deletion did not affect
      corticosterone responses elicited by LPS and by stressors. CONCLUSIONS: It
      appears that although p55 modulates the corticosterone-inducing effects of TNF
      alpha, the receptor does not play a critical role in the activation of the HPA
      axis by 'traditional' psychogenic stressors (noise, restraint) or systemic
      endotoxin challenge.

PMID- 15249731
TI  - Differential responses of circulating prolactin, GH, and ACTH levels and
      distribution and activity of submaxillary lymph node lymphocytes to calorie
      restriction in male Lewis and Wistar rats.
AB  - OBJECTIVES: Calorie restriction has been associated with anorexia in growing
      individuals, but the mechanisms involved are not known. Also, the effects of
      carbohydrates and lipid restriction in growing individuals were not studied. The
      aim of this study was to determine whether 66% calorie restriction (lipids and
      carbohydrates) differentially affects growing rats of the Wistar or Lewis
      strains. METHODS: Growing male Wistar and Lewis rats were subjected to 66%
      calorie restriction for 4 weeks. Plasma prolactin, growth hormone (GH), and
      adrenocorticotropic hormone (ACTH) levels were measured by specific
      radioimmunoassays. Likewise, lymphocytes from submaxillary lymph nodes were
      aseptically obtained to study absolute number of lymphocytes, cell surface
      markers (CD4+, CD8+, CD4+CD8+, B, and T cells), and proliferation. RESULTS: The
      body weight gain was lower in Lewis than in Wistar rats and was blunted in both
      strains by calorie restriction. Wistar and Lewis rats exhibited differential
      patterns of plasma prolactin, ACTH, and GH levels as well as proliferative
      capacities of T and B cells and their distribution in the submaxillary lymph
      nodes. Calorie restriction increased plasma prolactin and ACTH levels in Lewis as
      compared with Wistar rats. However, the plasma GH levels were diminished in both
      strains of rats by calorie restriction. All changes in plasma prolactin ACTH and
      GH levels seemed to correlate with the modifications observed in the
      distributions of T and B subsets in the submaxillary lymph nodes as well as in
      their proliferative capacity. CONCLUSIONS: Calorie restriction differentially
      modifies the secretory patterns of prolactin, GH, and ACTH in Lewis and in Wistar
      rats. These changes may explain, at least in part, the associated modifications
      in the proliferative capacity of submaxillary lymph node lymphocytes and in their
      distribution.

PMID- 15249732
TI  - Effects of fentanyl on natural killer cell activity and on resistance to tumor
      metastasis in rats. Dose and timing study.
AB  - OBJECTIVES: Opiates, which serve an integral role in anesthesia, suppress immune
      function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an
      important role in tumor and metastasis surveillance. We reported that large-dose
      fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing
      abdominal surgery. The immune modulatory effects of opiates may depend on the
      interaction between dose and time of administration. The present study examined
      the effects of different doses of fentanyl, administered at different time points
      relative to tumor inoculation, on NKCC and on experimental tumor metastasis in
      rats. METHODS: Fischer 344 rats were injected with low or high doses of fentanyl,
      6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously
      with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and
      lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was
      assessed 1 h after the fentanyl injection. RESULTS: At all time points, except 6
      h before tumor inoculation, fentanyl (0.1-0.3 mg/kg) induced a dose-dependent
      increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15
      mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC
      and increased MADB106 LTR in a correlated manner. CONCLUSION: These findings
      indicate that fentanyl suppresses NKCC and increases the risk of tumor
      metastasis. Suppression of NK cells at a time when surgery may induce tumor
      dissemination can prove to be critical to the spread of metastases. It is
      suggested that the acute administration of a moderate dose of opiates during
      surgery should be applied cautiously, particularly in cancer patients.

PMID- 15249733
TI  - Differential effects of rapid eye movement sleep deprivation and immobilization
      stress on blood lymphocyte subsets in rats.
AB  - OBJECTIVES: There is growing evidence of the relationship between sleep and the
      immune response. Studies aimed at elucidating the function of rapid eye movement
      (REM) sleep have found it difficult to separate the effects due to REM sleep
      deprivation and the effects due to the stress produced by the deprivation
      procedure. It has been claimed that immobilization is the main stressor that the
      animals have to face during the deprivation process. In this study, we analyzed
      the effects of short-term (24 h) and long-term (240 h) REM sleep deprivation on
      the distribution of lymphocyte subsets in the peripheral blood of rats. In
      addition, these effects were compared with those obtained after both short- and
      long-term stress by immobilization. METHODS: Lymphocyte population bearing
      surface markers such as CD5 (T cells), CD45RA (B cells), CD4 (T helper/inducer
      cells), CD8 (T suppressor/cytotoxic cells) and CD161 (NK cells) were analyzed
      using monoclonal antibodies. Lymphocyte subsets were assessed by flow cytometry.
      RESULTS: Both short- and long-term REM sleep deprivation decreased the percentage
      of T lymphocytes and induced a significant increase in NK cells. Short-term
      immobilization induced only a significant increase in the percentage of B
      lymphocytes and a decrease in the percentage of T lymphocytes, while long-term
      immobilization did not elicit any change. CONCLUSION: The present results support
      the notion that REM sleep deprivation and immobilization stress each exert
      particular effects on the immune system. These data suggest that the
      characteristics of the immune response will depend on the nature of the
      behavioral manipulation.

PMID- 15249734
TI  - Electroacupuncture enhancement of natural killer cell activity suppressed by
      anterior hypothalamic lesions in rats.
AB  - BACKGROUND/OBJECTIVE: Neuroendocrine hormones are derived from the hypothalamus.
      The central nervous system, particularly the hypothalamus, is capable of
      modulating the cytolytic activity of adherent natural killer (NK) cells. In
      addition, electroacupuncture (EA) stimulation of the Zusanli (ST36) acupoint
      enhances splenic NK cell and cytokine activities in rats. However, it is still
      unclear whether the anterior hypothalamus affects this immunomodulation.
      Therefore, the aim of the present study was to examine the effect of EA
      stimulation at the Zusanli acupoint on the NK cell activity modulated by an
      anterior hypothalamic area lesion. METHODS: Male Sprague-Dawley rats were used.
      Lesions were placed by means of a direct current through a concentric electrode.
      The electric acupuncture stimulation was delivered for 30 min per each experiment
      at the right ST36 acupoint with an electrical stimulator. The NK cell activity of
      the spleen was measured by a fluorescence assay. RESULTS: The NK cell activity
      was significantly reduced on the 2nd day after the lesion, but was restored to
      that of the sham group by the 7th day. However, when EA was applied for 2 days
      after the operation, the NK cell activity of the lesion group was restored to
      that of the sham group. After 7 days of EA, the NK cell activity of the lesion
      group was slightly higher than that of the sham group. CONCLUSION: From these
      results, we can suggest that EA enhances or restores the NK cell activity
      suppressed by an anterior hypothalamic area lesion.

PMID- 15249735
TI  - Benign multiple sclerosis is characterized by a stable neuroimmunologic network.
AB  - OBJECTIVES: Patients diagnosed with multiple sclerosis (MS) but without
      disability (Expanded Disability Status Scale score <2) form a specific group
      within those patients suffering from relapsing-remitting MS. Several
      neuroimmunologic effectors, including cytokines and melatonin, are known for
      their influence on the initiation of relapses and progression of the disease.
      METHODS: We evaluated 41 female patients with benign MS with respect to their
      clinical course, treatments and neuroimmunological parameters, including
      cytokines and melatonin. One subgroup was followed up for 7 years, and another
      group was evaluated during acute clinical relapse. RESULTS: The benign MS course
      in this homogeneous group of young patients was demonstrated by mild disease
      progression in 16% over 7 years. Initially, patients treated with azathioprine
      (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared
      to untreated patients, but not at follow-up. During acute relapse, treatment with
      corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as
      reduced type 1 cytokine levels. CONCLUSIONS: Our study supports the functional
      role of CS acting as an antiinflammatory protagonist during MS relapse, by
      inducing a shift towards predominance of type 2 cytokines. AZA showed a more
      subtle modulation of immune functions, reflected by reduced levels of the immune
      active hormone melatonin. During follow-up, it became apparent that stabilized
      levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained
      in concordance with the benign course of MS. These findings are in accordance
      with the hypothesis that benign MS is characterized by a balanced cytokine and
      neuroendocrine network, which is supported by immune-modulating therapies.

PMID- 15249736
TI  - Dopamine transporter as a marker of neuroprotection in methamphetamine-lesioned
      mice treated acutely with estradiol.
AB  - Our laboratories have shown the positive effect of estradiol on 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine- and methamphetamine (MA)-induced striatal dopamine
      (DA) depletion. Most studies on E neuroprotection use chronic administration of
      the steroid to evaluate its beneficial effect. In the present report, we
      investigated the neuroprotective potential of 17 beta-estradiol-3-benzoate (E)
      under acute conditions when administered 24, 12 or 0.5 h before MA. The effects
      of E on striatal DA and dihydroxyphenylacetic acid (DOPAC) contents, and DA
      transporter (DAT) protein and mRNA were measured using high-performance liquid
      chromatography, autoradiography and in situ hybridization, respectively. We
      observed neuroprotection with an acute dose of E, and also that protection
      presents a different time course for each dopaminergic marker. DAT mRNA responded
      more quickly to E than its protein (at 0.5 h vs. 24 h). Also, E treatment 12 h
      prior to MA resulted in 'normal' (equal to control) DA content, while DAT protein
      was still decreased as compared to control values. These different responses for
      each marker may represent different mechanisms of action of E (genomic versus
      nongenomic). Since most experimental studies use DA content as the sole indicator
      of nigrostriatal toxicity and examine a single time point following chronic E
      administration, the present results demonstrate the importance of evaluating
      differences in temporally dependent responses of DA, DAT protein and mRNA, to
      achieve a more comprehensive indication of the nigrostriatal state and the means
      by which E can function as a neuroprotectant in this system.

PMID- 15249737
TI  - Analysis of the contribution of galanin receptors 1 and 2 to the central actions
      of galanin-like peptide.
AB  - Galanin-like peptide (GALP) shares partial sequence identity with galanin and
      exhibits agonistic activity at two of the galanin receptor subtypes (GALR1 and
      GALR2) in vitro. The goal of these experiments was to determine whether galanin
      receptors mediate the effects of central GALP administration on food intake, body
      weight, and luteinizing hormone (LH) secretion in the mouse. We first evaluated
      the effects of intracerebroventricular injections of GALP or its vehicle alone in
      GALR1 knockout mice, GALR2 knockout mice, and their respective wild-type
      controls. GALP reduced food intake and body weight after 24 h to a similar degree
      in wild-type, GALR1 knockout, and GALR2 knockout mice. The wild-type, GALR1
      knockout, and GALR2 knockout mice also exhibited significant increases in serum
      levels of LH following the GALP injections. To help delineate the biologically
      active moiety of the GALP molecule, we injected wild-type mice with shorter
      fragments of the full-length GALP peptide. Neither GALP((1-21)) (the fragment
      containing the galanin-homologous sequence) nor GALP((22-60)) (the C-terminal
      portion of the GALP molecule lacking sequence identity with galanin) had any
      discernable effect on food intake, body weight or circulating LH. These
      observations demonstrate that neither GALR1 nor GALR2 are essential for mediating
      the effects of GALP on feeding, body weight or LH secretion. Furthermore, the
      galanin-homologous region of the GALP molecule is not sufficient to mimic the
      effects of full-length GALP. Together, these findings argue against the
      hypothesis that GALP signals solely through galanin receptors in vivoand suggest
      the existence of a yet-to-be-identified GALP-specific receptor.

PMID- 15249738
TI  - Decreased intercellular communication and connexin expression in mouse aortic
      endothelium during lipopolysaccharide-induced inflammation.
AB  - The role of gap junctional intercellular communication during inflammatory
      processes is not well understood. In particular, changes in the expression and
      function of vascular endothelial connexins (gap junction proteins) in response to
      inflammatory agents has not been fully investigated. In this study, we used
      intercellular dye transfer methods to assess interendothelial communication in
      aortic segments isolated from mice treated with or without intraperitoneal
      lipopolysaccharide (LPS), a potent inflammatory mediator. LPS treatment resulted
      in a 49% decrease in endothelial dye coupling 18 h after injection. Western blots
      indicated that LPS treatment also caused a reduction in endothelial connexin40
      (Cx40) levels to 33% of control levels. Connexin37 (Cx37) levels decreased only
      slightly after LPS treatment to 79% of control levels. We also examined
      endothelial communication in aortic segments isolated from Cx37-/- and Cx40-/-
      mice. LPS treatment caused a significantly greater decrease in dye transfer in
      endothelium isolated from Cx37-/- animals compared with endothelium from Cx40-/-
      animals (71 vs. 26% decrease). LPS injection caused a reduction in Cx40 levels in
      Cx37-/- endothelium, whereas LPS actually increased Cx37 levels in Cx40-/-
      endothelium. These results suggest that LPS mediates changes in endothelial gap
      junction-mediated communication, at least in part, through modulation of Cx40 and
      Cx37 levels.

PMID- 15249739
TI  - Insulin tolerance test causes hypokalaemia and can provoke cardiac arrhythmias.
AB  - We report the observation and analysis of a new adverse event during the insulin
      tolerance test (ITT) and propose additional safety procedures. An 8-year-old girl
      with growth hormone insufficiency had a cardiac arrest due to ventricular flutter
      when she was tested for growth hormone deficiency by the ITT. Severe hypokalaemia
      (K+ 2.6 mmol/l) was observed after resuscitation. Ergometry ECG revealed
      catecholaminergic polymorphic ventricular tachycardia, a hereditary
      arrhythmogenic disease. Consecutive measurements of serum potassium during ITT in
      29 short children (21 boys) with growth failure revealed a mean decrease of serum
      potassium by 1.1 +/- 0.4 mmol/l with the nadir at 30 min after the insulin bolus.
      Hypokalaemia (serum potassium < 3.5 mmol/l) occurred in all but one child; severe
      hypokalaemia (serum potassium < 2.9 mmol/l) was measured in every third child.
      This observation indicates that acute hypokalaemia which is induced by insulin
      and catecholamine excess occurs frequently in ITT. The case shows that the
      combination of acute hypokalaemia and the adrenergic counterregulation in ITT is
      a strong trigger of cardiac arrhythmias, which can become life-threatening if the
      child has an arrhythmogenic disease. Therefore, we recommend ECG monitoring
      during ITT to enhance the detection of cardiac arrhythmias. In addition, in the
      case of a comatose child during ITT the determination of the glucose and
      potassium level as well as adequate treatment are necessary.

PMID- 15249741
TI  - Fibrocystic disease of vulvar ectopic breast tissue. Case report and review of
      the literature.
AB  - INTRODUCTION: Mammary glands located in the vulvar region have been named as
      ectopic breast tissue or anogenital mammary glands by different authors.
      Literature on pathologies of ectopic breast tissue located in the vulvar region
      is rare. Most of the reports are about the malignancies arising from this ectopic
      tissue. CASE REPORT: We report a case of fibrocystic disease of the mammary
      glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated
      during pregnancy. CONCLUSION: Ectopic breast tissue in the vulva is a rare entity
      and fibrocystic disease of this tissue has rarely been reported in the English
      literature.

PMID- 15249740
TI  - Inhibition of growth hormone secretion in mild primary hyperparathyroidism.
AB  - INTRODUCTION: Impairment in growth hormone (GH) secretion has been reported to
      occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml)
      plasma PTH and free Ca levels. Patients with these characteristics are relatively
      few, whereas the great majority of patients with biochemically diagnosed PHP are
      asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels.
      We wondered whether also patients in these latter conditions show a defective GH
      secretory pattern. METHODS: In order to answer this question, 8 female subjects
      (mean age +/- SE: 44 +/- 1.3 years) were selected at the time of a checkup
      examination from a larger population of persons in fairly good clinical
      condition. Inclusion criteria were plasma PTH values slightly above the normal
      range (up to 50% higher than the maximum limit) with free Ca levels in the upper
      normal range or slightly higher (experimental group). Normal values in our
      laboratory are ionized calcium: 1.22-1.42 mmol/ml and plasma PTH: 12-72 pg/ml. A
      group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle
      normal range and significantly lower than values found in the experimental group
      was also selected and used as control. Experimental and control groups were
      tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30
      min and arginine plus GH-releasing hormone (GHRH; 1 microg/kg BW in an
      intravenous bolus injection). The GH responses to these challenging stimulations
      were compared between groups. RESULTS: Basal serum GH values were similar in all
      subjects. Both arginine and arginine plus GHRH induced a significant GH rise in
      both groups; however, the GH responses were significantly lower in the
      experimental than in the control group. Mean GH peak was 27.7 and 14.6 times
      higher than baseline after arginine and 57.5 and 26.6 times higher than baseline
      after arginine plus GHRH in the control and experimental group, respectively. No
      significant correlation was observed between PTH or Ca levels and the GH
      responses to challenging stimuli in any group. CONCLUSION: These data show that
      impairment in GH secretion is associated with slightly elevated levels of PTH in
      the presence of serum Ca values in the upper normal range. GH responses to
      stimulations were reduced by about 50% in our hyperparathyroid subjects. A long
      time duration of this relatively small decline of GH secretory activity may be
      supposed to contribute to age-related catabolic processes in a large number of
      patients with mild primary hyperparathyroidism.

PMID- 15249742
TI  - Nuclear dynamics of parthenogenesis of human oocytes: effect of oocyte aging in
      vitro.
AB  - We investigated in detail the nuclear kinetics of oocyte activation of aged human
      oocytes following combined activation treatment with calcium ionophore and
      puromycin. Two types of oocytes were used: (a) 1-day-old oocytes after 20-24 h
      retrieval, and (b) 2-day-old oocytes after 44-50 h retrieval. A total of 185
      unfertilized aged oocytes, 91 1-day-old and 94 2-day-old oocytes, were fixed at
      1, 2, 4, 6 and 8 h after activation treatment and then metaphase II (MII),
      anaphase or telophase II (A/T II) or pronuclear stage were recorded. We
      demonstrated that a combined calcium ionophore and puromycin treatment induced a
      high activation rate in both 1-day-old (95.6%) and 2-day-old oocytes (95.2%). Our
      results also demonstrated that the nuclear progression was faster in 2-day-old
      oocytes than in 1-day-old oocytes, although nuclear progression in
      parthenogenetically activated human oocytes requires the longer time periods
      compared with ICSI fertilization. It is concluded that combined treatment of the
      calcium ionophore and puromycin allows a high rate of parthenogenetic activation
      and the nuclear kinetics of parthenogenetically activated human oocytes appears
      to be more rapid in in vitro aging oocytes.

PMID- 15249743
TI  - Aberrant serum adiponectin levels in women with uterine leiomyomas.
AB  - BACKGROUND: Adiponectin is an adipocyte-secreted hormone. Serum adiponectin
      levels are inversely correlated with insulin resistance, and low plasma
      adiponectin levels have been demonstrated in type 2 diabetic patients. However,
      information on serum adiponectin levels in gynecological disorders is mostly
      lacking. In this study, we analyzed the possible correlation between serum
      adiponectin levels and uterine leiomyomas. METHODS: Serum adiponectin levels,
      determined by radioimmunoassay, were compared in women with uterine leiomyomas (n
      = 47) and normal controls (n = 46). RESULTS: Serum adiponectin levels in women
      with uterine leiomyomas (16.4 +/- 0.9 microg/ml) were significantly lower (p <
      0.05) than those in the normal controls (19.5 +/- 1.0 microg/ml). Furthermore,
      there was an inverse correlation between serum adiponectin levels and body mass
      index, in both women with leiomyomas and normal controls. CONCLUSIONS: Serum
      adiponectin levels are significantly decreased in myomatous patients.

PMID- 15249744
TI  - Botulinum toxin for the treatment of genital pain syndromes.
AB  - Our purpose was to test the effect of botulinum toxin injections on hypertonic
      pelvic floor muscles of patients suffering from genital pain syndromes. We report
      two cases of women complaining of a genital pain syndrome resistant to
      pharmacological therapies and rehabilitation exercises associated with a
      documented involuntary tonic contraction of the levator ani muscle as a defense
      reaction triggered by vulvar pain. We performed botulinum toxin injections into
      the levator ani with the intent to relieve pelvic muscular spasms. Within a few
      days after the injections both the patients reported a complete resolution of the
      painful symptomatology, lasting for several months. Our experience suggests that
      botulinum injections are indicated in patients with genital pain syndrome with
      documented pelvic muscle hyperactivity, whose symptoms arise not only from
      genital inflammation and lesions, but also, and sometimes chiefly, from levator
      ani myalgia.

PMID- 15249745
TI  - Intravenous leiomyomatosis with cardiac extension.
AB  - Intravenous leiomyomatosis with cardiac extension is an extremely rare uterine
      tumor. We report here a case of a patient with a uterine leiomyoma which extended
      into the right atrium through the left ovarian vein, progressing into the left
      renal vein along the inferior vena cava. Complete one-stage removal of the tumor
      was performed using cardiopulmonary bypass, and the patient has shown a favorable
      outcome. Successful therapy for intravenous leiomyomatosis is dependent on total
      surgical excision of the tumor, cessation of ovarian function and avoidance of
      postoperative estrogen replacement therapy.

PMID- 15249746
TI  - Hyperinnervation and mast cell activation may be used as histopathologic
      diagnostic criteria for vulvar vestibulitis.
AB  - OBJECTIVE: Vestibulitis is currently diagnosed based only on clinical criteria.
      To achieve histopathological diagnostic criteria, we carried out a computerized
      image analysis method. METHODS: Vestibular tissues removed from 40 women with
      severe vestibulitis were immunostained for mast cell count and degranulation by C
      kit and mast cell tryptase, respectively. Vestibular nerve cells total area was
      evaluated after S-100 stain. Controls were 7 women aged 18-48. The images were
      converted to a digital signal, and analyzed using Image Proplus V4 software.
      RESULTS: We found a significant increase in inflammatory infiltrate, number of
      mast cells and degranulated mast cells in vestibulitis compared to normal
      controls. The inflammatory cells were localized around the superficial minor
      vestibular glands. The total nerve fiber area was ten times higher in
      vestibulitis patients than in controls. A significant positive correlation was
      found between the total nerve fiber area and the number of mast cells in the
      vestibulitis group of patients. CONCLUSION: We documented two diagnostic
      histopathological criteria for vestibulitis: (1) the presence of eight or more
      mast cells per 10 x 10 microscopic field, and (2) the total calculated area of
      the nerve fibers is ten times higher than expected. These findings re-establish
      the inflammatory nature of the vestibulitis. It is speculated that the trigger
      for the local outburst of nerve fibers could be related to the activation of the
      mast cells by a topical agent.

PMID- 15249747
TI  - [Placebo: nuisance or the equally important other side of the coin?].

PMID- 15249748
TI  - Inhibition of (-)-trans-(1S,2S)-U50488 hydrochloride by its enantiomer in white
      mice -- a placebo-controlled, randomized study.
AB  - BACKGROUND: Previous studies have been performed to see if toxicity of optically
      active compounds may be inhibited by potentized preparations of their
      enantiomers. The present study is based on the hypothesis that the toxic effects
      of an optical isomer may be counteracted or reversed by the administration of a
      potentized preparation of one of its stereoisomers and in particular the
      enantiomer (patent applied for). METHODS: The design was prospective, blind,
      randomized, and placebo-controlled. 210 ICR conventional mice were used. 105 mice
      were administered a mixture of (+)-U50488 hydrochloride homeopathic potencies
      prior to and during the experiment, and the other 105 were administered
      indistinguishable placebo. The first 52 mice were used to establish an LD(50) of
      intraperitoneally administered (-)-U50488 hydrochloride under the conditions of
      this experiment. The estimated LD(50) was 25 mg/kg. The remaining 158 mice were
      then administered this LD(50) of (-)-U50488 HCl intraperitoneally. One mouse from
      the placebo group was excluded from the analysis because it died immediately
      after the possibly intravenous injection of (-)-U50488 HCl. RESULTS: 67% of
      homeopathy mice survived compared with 47% of placebo mice. The end point for
      statistical analysis was the difference in survival between the placebo and
      homeopathy mice. The analysis was adjusted for mouse weight using a logistic
      regression (LR) model. The LR treatment odds ratio for survival of treatment mice
      relative to placebo mice was 2.301 and the LR treatment chi-square was 6.2030 (1
      degree of freedom), which has a p-value of 0.0128. Consequently, we reject the
      null hypothesis of no treatment effect on survival. CONCLUSION: We conclude that
      toxicity of intraperitoneal injection of (-)-U50488 hydrochloride may be
      inhibited by administration of a mixture of potencies of its enantiomer.

PMID- 15249749
TI  - [Problems of randomized studies in complementary medicine demonstrated in a study
      on mistletoe treatment of patients with breast cancer].
AB  - BACKGROUND: Prospective randomized studies on mistletoe therapy repeatedly
      demonstrated that there is a basic problem in the matter of enrolling the
      appropriate number of patients within a reasonable amount of time. Most studies
      have to face this problem. However, recent experience suggests that this problem
      is more pronounced in the case of mistletoe treatment of cancer patients.
      OBJECTIVE: Possibility of recruitment and randomization of breast cancer patients
      for a mistletoe study. PATIENTS: During a period of 28 months every patient was
      registered who was admitted to the Gynecological Hospital of the University of
      Heidelberg because of suspected cancer. RESULTS: Out of 1,922 patients who were
      operated on for breast tumor, 521 first met the inclusion and exclusion criteria.
      154 out of these 521 patients agreed to take part in the study. After
      availability of the final results on tumor staging and the therapy plan for
      conventional treatment, 80 out of the 154 women had to be excluded from the
      study. From the remaining 74 patients (48%), however, only 29 (39%) would have
      agreed to take part in a randomized mistletoe study. CONCLUSIONS: This confirms
      our suspicion that the difficulties of enrollment and randomization in the case
      of mistletoe studies exceed those of studies conducted in conventional oncology.
      The reasons for this dramatic effect and the possibility of alternative study
      designs are discussed.

PMID- 15249750
TI  - [Health-related control belief and quality of life in chronically ill patients
      after a behavioral intervention in an integrative medicine clinic--an
      observational study].
AB  - BACKGROUND: In 1999 the Clinic for Internal Medicine and Integrative Medicine was
      founded in Essen as a regular part of the German inpatient health care system.
      Integrative medicine (standard internal medicine, evidence-based complementary
      and alternative medicine combined with intensified lifestyle modification) aims
      to help patients with chronic illness to cope with their condition more
      effectively and to achieve a health-promoting lifestyle. Techniques include
      cognitive restructuring, the elicitation of the relaxation response, and
      lifestyle education. The goal is to increase health-related quality of life (QoL)
      as well as control beliefs and to reduce morbidity in later life. AIM: To
      demonstrate changes in quality of life, lifestyle, and control beliefs after a
      two-week hospital stay. METHODS: Uncontrolled prospective observational study
      with 557 consecutive hospital patients. Outcome parameters were quality of life
      (SF36), control beliefs (GKU), and daily health-related behavior (nutrition,
      physical activity, relaxation) on admission, at discharge, as well as 3 and 6
      months after discharge. RESULTS: Weekly physical activity increases by 29%,
      consumption of not recommendable foods decreases by 18%. The majority of patients
      (57%) engage in relaxation exercises 6 months after discharge (on admission 23%).
      The physical sum scale (SF36) increases from 33.9 (95% KI 32.5-35.3) on admission
      to 37.3 (35.8-38.9) 6 months after discharge, the mental sum scale from 41.2
      (39.5-42.9) to 45.1 (43.5-46.7). The ratio internal/external control belief rises
      from 1.17 (95% KI 1.11-1.24) to 1.32 (1.24-1.40). Pretherapeutic ratio
      internal/external control belief and its increase are associated with rises in
      QoL. CONCLUSIONS: After integrative medicine treatment a lasting increase in QoL
      and lifestyle changes can be achieved. Reinforcement of internal control beliefs
      and own competence is possible and enhances outcomes in chronically ill patients.

PMID- 15249751
TI  - Bioresonance, a study of pseudo-scientific language.
AB  - Clarity of language is an essential element for effective communication. Using
      the example of bioresonance therapy, this article demonstrates how pseudo
      scientific language can be used to cloud important issues. This can be seen as an
      attempt to present nonsense as science. Because this misleads patients and can
      thus endanger their health, we should find ways of minimizing this problem.

PMID- 15249752
TI  - Surgery for peptic ulcer today. A study on the incidence, methods and mortality
      in surgery for peptic ulcer in Finland between 1987 and 1999.
AB  - BACKGROUND: During the past 20 years medical therapy of peptic ulcer disease
      (PUD) has dramatically improved. Simultaneously there has been a significant
      improvement in living and dietary habits. Quite presumably, all these significant
      events are reflected in the incidence and results of surgery for peptic
      ulcerations. AIM: To study the incidence, methods and mortality of surgery for
      PUD. METHODS: The nationwide data between 1987 and 1999 were obtained from the
      National Research and Development Centre for Welfare and Health. In the analysis
      the codes of the ICD 9-10 were used. RESULTS: The annual incidence of elective
      surgery for PUD decreased from 15.7 to 1.7 operations (per 10(5) inhabitants,
      mean of 2 consecutive years) between 1987 and 1999 (p < 0.05). Simultaneously,
      the annual incidence of emergency surgery increased from 5.2 to 7.0 operations
      (per 10(5) inhabitants, p < 0.05). In 1987, local procedures (duodeno
      /gastrorrhaphy or duodeno-/gastrostomy and suture) were applied in 25% of
      operations for PUD, whereas in 1999 they were 90% of the methods in PUD surgery.
      The overall annual mortality from PUD surgery remained 8% between 1987 and 1999.
      CONCLUSIONS: Elective ulcer surgery has virtually disappeared and parietal cell
      vagotomy has become history, whereas the incidence of emergency surgery increased
      significantly between 1987 and 2000, with the exception of the most recent years.
      Local procedures are overwhelmingly applied in emergency surgery and more
      extensive surgery is unnecessary. Nevertheless, the overall surgical mortality
      remained 8% between 1987 and 1999.

PMID- 15249753
TI  - Drug toxicity in the neonate.
AB  - The incidence of adverse drug reactions in neonates is thought to be at least
      10%. The physiology of the newborn infant is different to that of both paediatric
      patients and adults. This therefore predisposes to certain types of drug
      toxicity, which are described below. Medication errors are also a significant
      problem in the neonatal period due to the lack of appropriate formulations
      designed for neonates.

PMID- 15249754
TI  - Is there significant improvement in neonatal outcome after treating pPROM mothers
      with amnio-infusion?
AB  - The aim of this study was to determine the effects of amnio-infusion treatment on
      fetal and neonatal mortality and neonatal pulmonary development in women with
      singleton pregnancies and premature rupture of the membranes occurring at a
      gestational age of <26 weeks and who had severe oligohydramnios. The treated
      group of 45 consenting women received serial amnio-infusion and was compared with
      the control group of 44 women who underwent waiting treatment. Our study
      confirmed a higher number of live births in the treated group, especially in
      cases with a gestational age at rupture (GAR) of <20 weeks. Furthermore, even if
      GAR is an important factor for predicting pulmonary hypoplasia, amnio-infusion
      treatment reduces the probability of pulmonary hypoplasia. In fact, over 20
      weeks, amnio-infusion treatment significantly reduces the risk of pulmonary
      hypoplasia even if normal lung development cannot be guaranteed.

PMID- 15249755
TI  - Evaluation of stroke volume via arterial pulse pressure waveforms in neonatal
      lambs.
AB  - Arterial pulse waveforms contain information about stroke volume (SV) as an
      integral of pulsatile flow. SV estimation is accurate in adults with proper pulse
      pressure measurement technique. It is unclear whether the same methods are
      suitable in critically ill infants in the neonatal clinical setting where the
      fidelity of pulse pressure measurements are uncertain. We compared three pulse
      waveform SV methods with three systolic area SV methods in neonatal lambs in
      order to identify the most accurate and precise approach. Six newborn lambs were
      studied. Each lamb had a ligated ductus arteriosus and was instrumented to record
      high-fidelity pulsatile waveforms of arterial blood pressure using a transducer
      tipped catheter and pulsatile flow via calibrated ultrasonic flow probe,
      respectively. Three steady-state hemodynamic conditions were induced
      experimentally: control, hypertension via infusion of angiotensin II, and
      hypotension by phlebotomy. Recordings of a range of SVs were made during a steady
      state that was interrupted by a transient period of decreasing SV, induced by
      momentarily increasing preload by pulmonary artery occlusion. Modification of
      pulse wave pressure measurement conditions, simulating an overdamped fluid-filled
      catheter system, were achieved by low-pass digital filtering of the original high
      fidelity waveforms (high) to an 8-Hz cut-off (medium) and to a 2-Hz cut-off
      (low). The six SV estimates were then calibrated against flowmeter-derived SV and
      their accuracy and precision evaluated. Based on 6,479 waveforms, a systolic area
      method with pulse contour integration was the most accurate and precise. We
      conclude that neonatal pulse arterial waveforms embed SV information under a wide
      variety of hemodynamic and pressure waveform measurement conditions, and thus may
      be of potential clinical value in the assessment of newborn cardiovascular
      status.

PMID- 15249756
TI  - Effects of inhaled corticosteroids on systemic blood pressure in preterm infants.
AB  - OBJECTIVE: To assess the effect of inhaled fluticasone propionate on (i) systemic
      blood pressure, and (ii) the need for volume expanders (crystalloids and
      colloids) and inotropes for blood pressure support in preterm, very low birth
      weight (VLBW) infants. METHODS: Ventilated VLBW infants, less than 32 weeks of
      gestation, with respiratory distress syndrome were randomised to receive a 14-day
      course of either fluticasone propionate (500 microg/puff, 2 puffs every 12 h;
      n=27) or placebo (n=26) with a metered dose inhaler-spacer device. The response
      of treatment was assessed by comparing the use of volume expanders, inotropes,
      and the average and the lowest systolic, mean and diastolic blood pressures in 6
      hourly epochs between the 2 groups. RESULTS: There were no significant
      differences in the average or the lowest systolic, mean and diastolic blood
      pressures in 6 hourly epochs between the 2 groups. However, the total volume of
      crystalloids and colloids requirement was significantly greater in control than
      in treated infants (p=0.03). There was also a trend towards greater consumption
      of the total cumulative dose of dopamine in the control infants (p=0.10).
      CONCLUSIONS: Fluticasone-treated infants required significantly less volume of
      crystalloids and colloids for blood pressure support compared with control
      infants. Further larger scale studies are required to determine whether inhaled
      corticosteroids could minimise the use of volume replacement therapy and
      inotropes in the treatment of hypotension in preterm infants in the early
      postnatal period.

PMID- 15249758
TI  - Diagnosis of acute renal failure in very preterm infants.
AB  - This study was designed to improve the definition of acute renal failure (ARF) in
      very preterm infants. Twenty-eight newborn infants with gestational age < or =32
      weeks were prospectively studied in the first 5 days of life and made up a
      control group as they did not present risk factors for vasomotor renal
      insufficiency. Renal insufficiency was defined as an increase in daily serum
      creatinine concentration above the 99th interval limit obtained in this control
      group, i.e., 43 micromol/l on day 1 and/or 21 micromol/l on day 2 and/or 14
      micromol/l/day on day 3 and/or 22 micromol/l/day on day 4. According to this
      definition, 20 very preterm infants with ARF were identified. As compared with
      the control group, the ARF group showed more prolonged oliguric episodes, lower
      diuresis, insufficient weight loss (in spite of a reduction in water intake) and
      also more episodes with natremia <130 mEq/l (35 vs. 0%; p <0.05) and/or kalemia
      >6 mEq/l (40 vs. 11%; p <0.05). Therefore, assessment of daily changes in serum
      creatinine concentration in very preterm infants allows the diagnosis of
      clinically significant reduction in glomerular filtration rate.

PMID- 15249757
TI  - Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of
      amikacin in preterm infants during the first days of life.
AB  - The aim of this study was to assess the effects of intravenous co-administration
      of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of
      life in preterm infants. The pharmacokinetics of amikacin were retrospectively
      calculated in a cohort of 73 neonates (gestational age <31 weeks) who received
      either ibuprofen-lysine or placebo following inclusion in the multicentre
      ibuprofen prophylaxis study. Assuming a one-compartment model with instantaneous
      input and first-order output, there was no significant difference in the median
      distribution volume (0.63 vs. 0.59 liters/kg), but the median serum half-life
      (16.4 vs. 12.4 h) of amikacin was significantly longer (p <0.02), and the
      clearance (0.36 vs. 0.6 ml/kg/min; p <0.005) of amikacin was significantly lower
      in infants who received ibuprofen-lysine. We conclude that the time interval
      between consecutive amikacin administrations should be prolonged, if ibuprofen
      lysine is co-administered.

PMID- 15249759
TI  - Fasting respiratory quotient as a predictor of long-term weight changes in non
      obese women.
AB  - BACKGROUND/AIMS: The identification of metabolic and environmental predictors of
      excess body fat is still far from being achieved. The aim of this study was to
      evaluate whether respiratory quotient in non-obese women is a predictor of body
      weight changes after a 6-year follow-up period. METHODS: Forty-three non-obese
      healthy women participated in the study. Their baseline general characteristics
      were: age 40.5 +/- 12.8 years; height 159 +/- 7 cm; weight 61.8 +/- 10.1 kg, and
      body mass index (BMI) 24.4 +/- 3.8 kg/m2. At baseline basal metabolic rate and
      respiratory quotient were determined by indirect calorimetry, while weight and
      BMI were recorded at the first observation and after the 3- and 6-year follow
      ups. RESULTS: At the first observation basal metabolic rate was 5,360 +/- 713
      kJ/day and respiratory quotient 0.850 +/- 0.052. After 6 years, with weight
      changes equal to 1.4 +/- 4.5 kg, baseline respiratory quotient was a significant
      predictor (p < 0.05) of changes in body weight or BMI together with baseline BMI.
      CONCLUSIONS: This follow-up study confirms that a high respiratory quotient
      (measured on free diet) predisposes to weight gain, especially in women with the
      highest baseline respiratory quotient (above the 90th percentile of the
      distribution for this variable).

PMID- 15249760
TI  - A step in the right direction for the coronary artery calcium score.

PMID- 15249761
TI  - Elevated levels of low-density lipoprotein cholesterol, homocysteine, and
      lipoprotein(a) are associated with the occurrence of symptomatic bypass graft
      disease 1 year following coronary artery bypass graft surgery.
AB  - Severe coronary artery bypass graft disease occurs at a rate of approximately 16%
      31% within the first year of surgery. Clinical and laboratory variables,
      including postoperative lipid profiles closest to the 1-year follow-up,
      lipoprotein(a) levels, and homocysteine levels, were assessed as predictors of
      early (< or = 1 year) symptomatic coronary artery bypass graft disease. Of 77
      living consecutive patients (from the practice of one cardiologist) who underwent
      bypass surgery, 60 were asymptomatic at 1 year, and 17 had developed recurrent
      symptoms and had an angiogram that confirmed >50% lesion in at least one
      saphenous bypass graft. Using multivariate analysis, the strongest predictors of
      early symptomatic coronary artery bypass graft disease within 1 year of bypass
      surgery were elevated levels of low-density lipoprotein cholesterol (>100 mg/dL)
      (odds ratio [OR], 8:1; p=0.034), homocysteine (>10 micromol/L) (OR, 8:1;
      p=0.019), and lipoprotein(a) (>30 mg/dL) (OR, 4:1; p=0.011). Male gender was
      associated with a reduced risk (OR, 1:9; p=0.01) of symptomatic graft disease
      within 1 year of surgery. The authors conclude that low-density lipoprotein,
      homocysteine, and lipoprotein(a) levels are associated with symptomatic coronary
      artery bypass graft disease at 1 year after surgery.

PMID- 15249762
TI  - Body composition profiles derived from dual-energy X-ray absorptiometry, total
      body scan, and mortality.
AB  - Little has been reported on the association of derived body composition data and
      cardiovascular mortality. The authors defined body composition profiles based on
      one- and two-variable measures from dual-energy x-ray absorptiometry (DXA) total
      body scans. Scan results are labeled "apple" if Z score for percent of total fat
      in trunk is >0 and "pear" if Z score for height-corrected limb fat is > or = 0.
      The fat measures were combined to define four body composition profiles:
      "pickle," "avocado," "mango," and "barrel." A third axis, the Z score of height
      corrected limb lean tissue, is an index of skeletal muscle mass and was used to
      label subjects as "hard" or "soft." Subjects (n=324) who were in good health from
      Malmo, Sweden, underwent body composition analysis using DXA and were followed
      for 10 years. The distribution of body composition profiles was similar for both
      genders and across age groups. Among subjects aged 50-74 years at baseline
      (n=116), there were 21 deaths. Barrel had the highest mortality rate: 13/39
      (33.3%) mortality for barrels, compared with 8/77 (10.4%) mortality for non
      barrels; mortality odds ratio, 3.2; 95% confidence interval, 1.45-7.08. The
      increased mortality was principally attributable to cardiovascular cause-related
      deaths. Soft (sarcopenia) was also associated with increased mortality (25.9%;
      p=0.05), but not cardiovascular cause-related deaths, whereas the total mortality
      among apples was not significantly increased but cardiovascular cause-related
      deaths were predominant (75%; p=0.02). The authors propose that DXA-body
      composition profiles can identify increased mortality risk of magnitude similar
      to major cardiovascular risk factors and may prove useful in health assessment.

PMID- 15249763
TI  - Body size and cardiovascular risk factors in a preschool population.
AB  - Data on weight, height, blood pressure, and blood lipids were obtained for 1215
      children entering New York Head Start preschools from 1995-1997. In this
      population, 17% were overweight and 15% were obese; the risk was greatest in
      Hispanic children. Overall, 13% had high blood pressure. African-American
      children were at increased risk of elevated blood pressure but had a more
      favorable lipid profile (high high-density lipoprotein cholesterol level and low
      triglycerides level) than white or Hispanic children. Body size was a significant
      predictor of elevated blood pressure, low high-density lipoprotein cholesterol,
      and increased triglycerides. The association between obesity and blood pressure
      was evident in white and Hispanic children only. Neither ethnicity nor obesity
      was associated with total cholesterol level. Obese preschoolers had approximately
      three times the risk of having high systolic blood pressure and twice the risk of
      low high-density lipoprotein cholesterol level compared with nonobese children,
      indicating that at-risk populations can be identified and primary prevention
      begun at a young age.

PMID- 15249764
TI  - Non-high-density lipoprotein cholesterol: an alternate target for lipid-lowering
      therapy.
AB  - Non-high-density lipoprotein (non-HDL) cholesterol level is determined by
      subtracting the high-density lipoprotein cholesterol level from the total
      cholesterol level and thus encompasses not only low-density lipoprotein
      cholesterol, but also the cholesterol contained in atherogenic, triglyceride-rich
      particles like remnants. This review summarizes data extracted from English
      language publications accessible through MEDLINE on the population distribution
      of non-HDL cholesterol, its relationship to cardiovascular disease, and the
      potential benefits of treatment. Non-HDL cholesterol levels in the population
      vary by age, sex, and race and are closely linked to measures of obesity,
      especially visceral obesity. Several studies in populations with and without
      cardiovascular disease show that non-HDL cholesterol levels relate to
      atherosclerosis severity and subsequent cardiovascular morbidity and mortality.
      Preliminary data also suggest that pharmacologically induced changes in non-HDL
      cholesterol levels relate to prognosis. In the National Cholesterol Education
      Program Adult Treatment Panel III report, non-HDL cholesterol has been designated
      a secondary target of therapy among patients with hypertriglyceridemia.

PMID- 15249765
TI  - Coronary heart disease risk reduction in postmenopausal women: the role of statin
      therapy and hormone replacement therapy.
AB  - The incidence of coronary heart disease in women rises sharply in the years
      following menopause, and prescribing of hormone replacement therapy in the belief
      that it might compensate for the loss of estrogen-mediated cardioprotection is
      widespread. However, controlled trials have failed to show a beneficial effect of
      hormone replacement therapy on the incidence of coronary events, and recent
      evidence suggests that hormone replacement therapy may even have a deleterious
      effect on primary coronary heart disease prevention. Statins are recommended as
      first-line treatment for lowering low-density lipoprotein cholesterol levels in
      women and are extremely valuable in reducing coronary heart disease risk in this
      group. An awareness of the benefits of appropriate statin treatment, and evidence
      showing that they can be safely added to hormone replacement therapy prescribed
      for the relief of menopausal symptoms and osteoporosis, provides the opportunity
      to optimize clinical outcomes for coronary heart disease among the large and
      expanding population of postmenopausal women.

PMID- 15249766
TI  - Suboptimal therapy of heart failure: a continuing theme.

PMID- 15249768
TI  - Predictors of physical function in patients with peripherial arterial disease and
      claudication.
AB  - Limitation of walking due to claudication is the hallmark of peripheral arterial
      disease. The purpose of this secondary analysis was to identify biobehavioral
      predictors of physical function in peripheral arterial disease patients that
      included walking ability, gender, age, disease severity, environmental factors
      (social support), and medical comorbidity (arthritis). All subjects performed an
      exercise treadmill test to determine initial and absolute claudication distance.
      The sample consisted of 97 peripheral arterial disease patients, 71 (73%) men and
      26 (27%) women, with a mean age of 73+/-8 years (range 52-90 years). Initial
      claudication distance occurred at 171.88+/-136.35 m. Absolute claudication
      distance was 421.03+/-286.37 m. A simultaneous multiple regression analysis was
      performed to determine predictors of physical function. The model accounted for
      35% of the variance (p<0.001) and included personal characteristics (age, gender,
      years of education), severity of disease by ankle-brachial index, environmental
      factors of social support (marital status), absolute claudication distance, and
      arthritis. Education (p=0.011), absolute claudication distance (p=0.014), social
      support (p=0.026), arthritis (p=0.028), and age (p=0.033) were the strongest
      predictors of physical function. This study identifies biobehavioral factors that
      place peripheral arterial disease patients at greater risk for reduced physical
      function and provides a rationale for interventions that improve walking ability.

PMID- 15249769
TI  - Nursing education and implications for left ventricular assist device destination
      therapy.
AB  - The HeartMate VE Left Ventricular Assist Device (vented electric abdominally
      positioned pulsatile blood pump; Thoratec Corp., Pleasanton, CA), approved as a
      permanent support, or destination therapy, by the US Food and Drug Administration
      in 2002 and Medicare in 2003, is now a potential therapy for numerous patients.
      Postimplantation nursing care is crucial to the success of left ventricular
      support device therapy and long-term recipient outcome. Nurses also contribute to
      cost containment, making this a viable treatment for the facility and the
      patient. Consequently, nurses must be educated about left ventricular assist
      device concepts and challenges, the benefits of device placement, intensive care
      unit and postintensive care unit daily care requirements, and outpatient
      preparation. This knowledge will enable nurses to provide necessary care and to
      educate recipients, families, and community health care providers on how to give
      appropriate posthospital care.

PMID- 15249770
TI  - Care of elderly patients with chronic symptomatic coronary artery disease: is it
      TIME to be more offensive?
AB  - Young patients with coronary artery disease usually benefit from
      revascularization in terms of symptom relief and outcome. There are no
      prospective data available, however, for patients older than age 75 years, for
      whom quality of life might be more of an issue than quantity of life and for whom
      risk profiles and comorbidities make treating physicians more reluctant to
      prescribe an invasive procedure. The recently published Trial of Invasive vs.
      Medical therapy in Elderly patients (TIME) was the first to address patients > or
      =75 years of age with chronic angina despite standard medical therapy. The
      authors discuss the benefits and risks of interventional vs. medical management
      of chronic, symptomatic coronary artery disease in elderly patients in view of
      the TIME results and their clinical implications.

PMID- 15249771
TI  - Educating patients with diabetes about cardiovascular disease risk.
AB  - In persons with diabetes mellitus, atherosclerosis is increased, develops
      prematurely, and is associated with an accelerated progression of atherosclerotic
      changes. More than 55% of deaths from diabetes are from cardiovascular disease.
      Central to the optimal management of diabetes and the prevention of chronic
      complications is effective patient education. The necessity of optimal glycemic
      control in the prevention of long-term diabetes-related complications,
      particularly microvascular disease, has been a primary focus of diabetes
      education during the past decade. It has become clear that to prevent
      cardiovascular disease in persons with diabetes, an increased emphasis on patient
      education aimed at reducing cardiovascular disease risk factors is essential.
      This review explores the scope, impact, and prevention of diabetes-related
      cardiovascular disease, focusing on integration of cardiovascular disease risk
      reduction during patient teaching and education programs.

PMID- 15249772
TI  - Cardiovascular nursing in Hong Kong.

PMID- 15249774
TI  - Decreasing the risk of ventilator-associated pneumonia: the impact of nursing
      care.

PMID- 15249773
TI  - Cardiovascular implications of thiazolidinedione therapy.
AB  - The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States
      has been increasing dramatically over the past 15 years, and is now at epidemic
      proportions. DM2 is the clinical manifestation of a long-term metabolic process
      that is initiated by cells' decreased sensitivity to the actions of insulin. Many
      outcome studies have identified DM2 as a strong and independent risk factor for
      the development of cardiovascular complications such as hypertension,
      arteriosclerosis, and heart failure. The goals of therapy in treating DM2 are to
      improve the long-term outlook for these patients. However, in selecting a
      therapeutic regimen for patients, clinicians should be aware that potentially
      severe adverse events may occur at a rate not previously identified in phase 3
      studies. Certain therapies used to treat DM2, by effectively increasing the
      sensitivity of insulin, have also been reported to cause adverse effects, which
      can precipitate symptomatic heart failure. The purpose of this column is to
      discuss the therapeutic options available for treating patients with DM2, the
      potential pathophysiology of the adverse events of symptomatic heart failure,
      encouragement of use of the US Food and Drug Administration MedWatch program for
      reporting adverse events associated with medication therapy, and review of newer
      treatment guidelines for use of insulin-sensitizing agents in patients with
      chronic heart failure.

PMID- 15249775
TI  - When is ST segment elevation not indicative of acute coronary syndrome?

PMID- 15249777
TI  - Symbols for dermatologists.

PMID- 15249776
TI  - Quackery and the dermatologist.

PMID- 15249778
TI  - Reflections on Mohs micrographic surgery.

PMID- 15249779
TI  - A primer of Mohs micrographic surgery: common indications.
AB  - Mohs micrographic surgery is a highly effective technique for the removal of some
      skin cancers. The technique is founded on the idea of excision with minimal
      margins (sparing normal tissue) and immediate histologic examination of
      horizontal frozen sections of the specimen while the patient waits. By doing
      this, a Mohs surgeon is able to examine the margins. If residual tumor is
      present, subsequent excisions are performed until it is completely removed. In
      cases of aggressive tumors, recurrent tumors, or in which the lesions are present
      in high-risk anatomic locations (H-zone of the face) or functionally important
      areas (e.g., digits, genitals), the preferred treatment is Mohs micrographic
      surgery.

PMID- 15249780
TI  - Smallpox: what the dermatologist should know.
AB  - Despite the eradication of naturally occurring smallpox in 1977, stores of the
      virus have been maintained in laboratories in the United States and Russia. It is
      feared that certain rogue states and terrorist organizations may have illicitly
      acquired the virus with the intent of unleashing it as an agent of bioterrorism.
      The United States and other nations have begun vaccinating individuals in the
      military and health care workers who might become exposed. Primary care providers
      and dermatologists will be called upon to evaluate potential index cases and
      vaccination reactions. In this report, the authors review the essential clinical
      aspects of smallpox and potential reactions to smallpox vaccination. Special
      attention is given to eczema vaccinatum, which can occur in vaccinees and their
      family contacts with active or quiescent atopic dermatitis or a personal history
      of eczema.

PMID- 15249781
TI  - Diseases on hair follicles leading to hair loss part I: nonscarring alopecias.
AB  - Hair follicles are unique structures with exceptional regenerative potential.
      They are believed to be crucial for epidermal homeostasis and reepithelialization
      after damage to human skin. Like other, more active and quickly proliferating
      organ systems, hair follicles may be easily disturbed in their normal growth
      cycle by systemic and local influences, including specific skin diseases. This
      may lead to hair loss, a very common complaint in men and women. The difficulties
      in reviewing the diseases of hair follicles lay in the long list of different
      etiologic factors (infectious, autoimmune, inflammatory, neoplastic, physical,
      chemical, congenital) and a still missing classification system according to
      etiopathogenetic principles. In this article (Part I of II), the structure and
      function of hair follicles, the diagnostic approach to diseases causing hair
      loss, and the most common nonscarring alopecias (telogen effluvium, anagen
      effluvium, androgenetic alopecia, and alopecia areata) are reviewed in regard to
      pathogenesis, clinical findings, and current options of treatment. Part II will
      focus on scarring alopecias.

PMID- 15249782
TI  - New therapy update: ALDARA (imiquimod cream, 5%).

PMID- 15249783
TI  - Infectious disease capsules: a pox on your house.
AB  - A 31-year-old, previously healthy white man presented to the emergency department
      with complaints of malaise, fevers, shortness of breath, a non-productive cough,
      and a "rash." His physical exam revealed a temperature of 100.2F, a pulse of 129
      bpm, respiratory rate of 14 BPM, and blood pressure of 140/74 mm Hg. He was
      alert, oriented, and in no distress. His oropharynx was dry, his neck was supple,
      and cervical lymphadenopathy was absent. He had tachycardia, bilateral wheezes,
      and rhonchi with prolonged expirations. There was a diffuse vesicular eruption
      enveloping his entire body with involvement sparing his palms and soles (Figures
      1 and 2). Laboratory values showed a hemoglobin of 16.0 g/dL and a white blood
      cell count of 7100 cells/pL, with 39%neutrophils, 23% bands, and 35% lymphocytes.
      His platelet count was mildly decreased to 86,000 x 103/pL. Chest radiograph
      revealed bilateral diffuse interstitial infiltrates. A diagnosis of acute
      varicella-zoster virus pneumonia (varicella pneumonia) was made, and the patient
      was started on IV acyclovir (10 mg/kg every 8 hours). Upon further questioning,
      the patient stated that his daughter had been diagnosed with "chickenpox" 7 days
      ago. The patient had numerous exposures to chickenpox in the past but had never
      developed clinical expressions of varicella. He was not at risk for HIV
      infection, not having multiple sexual partners, IV drug abuse, or blood
      transfusions. During the 1 day of in-hospitalization, his fever abated and the
      pulmonary signs diminished. Following discharge, IV acyclovir was replaced by
      valacyclovir to complete a 7-day course of therapy.

PMID- 15249784
TI  - Instrument capsules: laser hair removal in pigmented skin.
AB  - A 50-year old African-American woman presented to her physician's office seeking
      treatment of excess hair and secondary hyperpigmentation of her chin. On exam,
      her skin was noted to be Fitzpatrick Type V and her hair was course and dark.

PMID- 15249785
TI  - Surgical capsules: diagnosis and management of liposarcoma.
AB  - A healthy, 53-year-old man presented with a small, soft, nontender mass of his
      right upper arm that progressively grew larger and more firm during the 6 weeks
      before evaluation.

PMID- 15249786
TI  - Common diseases/treatment options: treatment options for psoriasis part 1:
      topical treatments.
AB  - A 40-year-old Hispanic man presented for treatment of dermatitis on his elbows
      and knees that had been evident for 5 years (Figure 1). He also had scaling
      plaques on his scalp. He had not been treated previously. He did not have any
      other medical problems and did not complain of arthritis. A clinical diagnosis
      was made of psoriasis and he was prescribed clobetasol propionate ointment with
      salicylic acid 6% in petrolatum that should be applied in the evening to his
      elbows and knees and calcipotriene ointment with clobetasol that should be
      applied in the morning. For his scalp, he was prescribed betamethasone valerate
      foam 0.12% to be applied directly to the scalp once a day and told to use a tar
      shampoo contain-ing 4% neutar solubilized coal tar extract (1.0% coal tar) three
      times a week. He followed this regimen for 2 weeks and the plaques became much
      less keratotic. He continued his scalp regimen. He then started using
      calcipotriene ointment and clobetasol propionate ointment together twice a day.
      Three weeks later the plaques were much flatter and less erythematous. The
      patient was instructed to apply clobetasol propionate to the affected areas twice
      a day on Saturday and Sunday and calcipotriene twice a day Monday through Friday.
      At this point, his scalp was almost clear and the patient was told touse the foam
      as necessary and to continue the shampoo.

PMID- 15249788
TI  - Case study: erythrokeratodermia variabilis.
AB  - A 4-year-old girl presented to the dermatology clinic with complaints of
      erythematous skin lesions on her face, extremities,forearms, and joints. The
      patient was a product of a full-term, normal pregnancy and delivery and was born
      to healthy parents. The parents are cousins. The condition started a few months
      after birth with small, hyperkeratotic patches on her cheeks. These lesions did
      not respond to the treatment that was given. The condition progressed and a few
      months later similar skin lesions started to appear on her forearms and knees.
      Different types of treatment, such as topical antibiotics,emollients, topical
      steroids, and systemic antihistamines, have been tried without any benefit. Some
      lesions showed variable exacerbations and remissions. There was no family history
      of a similar problem, although her older brother showed marginal hair loss
      without any skin lesions. On physical examination (Figures 1-3), hyperkeratotic
      erythrodermic plaques of variable thickness with sharply demarcated borders were
      seen on cheeks, extensor surfaces of forearms, and on the knees. The palms,soles,
      nails, and teeth were normal. The hair showed normal appearance, but there was no
      hair growth on the margins of the scalp. The laboratory investigations showed
      normal complete blood count and normal serum zinc and ferritin levels. Urine
      microscopy and examination was normal. Skin biopsy was taken and histopathology
      showed nonspecific features of hyperkeratosis with moderate papillomatosis and
      acanthosis (Figure 4). A diagnosis of erythrokeratodermia variabilis was made and
      the patient was started on emollients as treatment. There was not much
      improvement with the treatment.

PMID- 15249787
TI  - Myths and misconceptions: the risk of melanoma in small congenital nevi.
AB  - A 2-year-old boy presents with a 4 x 3-cm, darkly pigmented nevus on his back.
      His mother states that this lesion has been present since birth. Both parents
      noticed that the nevus has become slightly larger but deny any other changes in
      its appearance. The boy is otherwise healthy. He has no allergies and does not
      take any medication. There is no family history of skin disease or cutaneous
      malignancy. The parents are concerned about the melanoma risk in their child's
      congenital nevus.

PMID- 15249790
TI  - Random thoughts on guidelines: how are they determined? are they followed?

PMID- 15249789
TI  - Case study: pachyonychia congenita: a mixed type II-type IV presentation.
AB  - A 52-year-old woman in good health with a family history negative for
      dermatologic diseases presented to our department with thickening and dystrophy
      of all her fingernails and toenails that started when she was born. She also had
      hyperkeratosis on the palms of her hands and soles of her feet that was confined
      to sites of pressure and recurrent plantar blisters that began appearing at
      puberty. The patient reported marked pain while walking from such plantar
      involvement. Her medical history revealed a persistent hoarseness; palmoplantar
      hyperhidrosis; and the appearance of numerous cysts on her back, neck, and scalp
      since she was 20 years old. These latter lesions had been diagnosed as multiple
      steatocystoma on the basis of the histologic features. Upon examination, all of
      her fingernails and toenails appeared shortened, thickened,and dystrophic
      (Figures 1-3). In addition, they presented subungual keratosis and a yellowish
      gray color. Hyperkeratosis and small ulcerations were present on the
      perionychium. Palmoplantar keratoderma was evident, especially on the soles,in
      association with superficial erosions (Figure 4). Keratosis pilaris was evident
      on the extensor surfaces of the forearms as well as on the anterior surfaces of
      the legs. Multiple nodules were detected on the patient's neck, trunk, and
      axillary regions(Figure 5). They consisted of multiplex steatocystoma and were
      characterized by a hemispheric shape, a normal-appearing skin color, and by an
      elastic consistency on palpation. Oral and dental changes were not detected,
      although hair anomalies were evident. Laboratory parameters disclosed
      eosinophilia and increased total IgE levels. The results of serum protein
      electrophoresis was normal, as were those concerning hepatic and renal functions.
      The ophthalmology examination showed neither corneal dyskeratosis nor cataracts.
      The neurologic-psychiatric visit revealed slight mental retardation.

PMID- 15249791
TI  - Obesity and high blood pressure: a clinical phenotype for the insulin resistance
      syndrome in African Americans.
AB  - The high prevalence of insulin resistance syndrome in African Americans
      predisposes this population to higher morbidity and mortality from cardiovascular
      disease. To test the hypothesis that the combination of obesity and high blood
      pressure (BP) represents the physical phenotype of insulin resistance syndrome,
      337 African-American men and women aged 32+/-4 years were examined and classified
      into four groups (nonobese-normal BP, nonobese-high BP, obese-normal BP, obese
      high BP), according to presence or absence of obesity and high BP. Mean values of
      glucose, insulin, lipids, urinary albumin excretion, and clamp-derived insulin
      sensitivity were determined for each group. Prevalence of prediabetes (24.4%),
      diabetes (19.2%), and insulin resistance syndrome (87.2%) were highest in the
      obese-high BP group (p<0.001). Mean triglycerides, urinary albumin excretion,
      fasting glucose, fasting insulin, and insulin resistance were highest in the
      obese-high BP group (p<0.001). Subjects with both obesity and high BP showed
      greater expression of lipid and glucose abnormalities, higher urinary albumin
      excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and
      insulin resistance syndrome.

PMID- 15249792
TI  - Effect of the dietary approaches to stop hypertension diet and reduced sodium
      intake on blood pressure control.
AB  - The authors hypothesized that the Dietary Approaches to Stop Hypertension (DASH)
      diet and reduced sodium intake would control stage 1 hypertension and reduce high
      normal blood pressure (BP) to optimal levels. Adults with systolic BP 120-159 mm
      Hg and diastolic BP 80-95 mm Hg were randomly assigned to receive the DASH diet
      or a typical American (control) diet, consuming three different sodium intakes
      (higher=142 mmol/d, intermediate=107 mmol/d, and lower=65 mmol/d) for 30 days
      each. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm
      Hg. Among subjects with hypertension at baseline, at higher sodium intake the
      DASH diet increased BP control two-fold over control (63% vs. 32%; 95% confidence
      interval, 1.4-2.9). Reducing sodium intake in the control diet group increased BP
      control 2.3-fold (74% vs. 32%; 95% confidence interval, 1.7-3.2). The maximum BP
      control rate (84%) was achieved with the DASH/lower sodium diet. BP became normal
      or optimal in 71% of persons consuming the control/lower sodium diet and 77% of
      persons consuming the DASH/lower sodium diet. Both the DASH diet and reduced
      sodium intake improved BP control.

PMID- 15249793
TI  - Healthy diet and blood pressure.

PMID- 15249794
TI  - Comprehensive lifestyle modification and blood pressure control: a review of the
      PREMIER trial.
AB  - The PREMIER trial assessed the aggregate effect on blood pressure (BP) of
      nationally recommended lifestyle modifications in free-living adults with high
      normal (stage 1) hypertension. Participants (N=810) were randomized to the advice
      only group; the established group (consisting of weight loss, increased physical
      activity, and reduced sodium and alcohol intake); or the established plus Dietary
      Approaches to Stop Hypertension (DASH) diet group (consisting of the established
      interventions in addition to the DASH dietary pattern). The primary outcome was
      change in systolic BP at 6 months. Net of advice only, mean systolic BP declined
      by 3.7 mm Hg for members of the established group (p<0.001) and 4.3 mm Hg for the
      established plus DASH group (p<0.001). The prevalence of hypertension decreased
      from a baseline of 38% to 17% in the established group (p=0.01) and to 12% in the
      established plus DASH group (p<0.001) compared with a decrease to 26% in the
      advice-only group. The PREMIER trial demonstrated that persons with above-optimal
      BP and stage 1 hypertension can make multiple lifestyle changes leading to better
      control of BP.

PMID- 15249795
TI  - Interview with Louis Tobian, MD. Interview by Marvin Moser.

PMID- 15249796
TI  - Hypertensive risk assessment: cardiovascular risk factors and hypertension.

PMID- 15249797
TI  - Case studies in hypertension: managing calcium channel blocker-related peripheral
      edema.

PMID- 15249798
TI  - Reflections in hypertension: work and blood pressure.

PMID- 15249800
TI  - Angiotensin-converting enzyme inhibitors side effects--physiologic and non
      physiologic considerations.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are increasingly recognized as
      having an important role in the treatment of hypertension and/or end-organ
      disease. The sheer number of ACE inhibitors in the United States--now numbering
      10 different chemical entities--has created a sense of comfort with these
      compounds, which is particularly evident when these compounds are used in the
      patient with essential hypertension; conversely, when comorbid conditions are
      present in the ACE inhibitor-treated patient, circumstances change and physician
      vigilance becomes more of a necessity. ACE inhibitor therapy in patients with
      either cardiac and/or renal disease is as much an art as it is a science, and
      even in the most skilled hands can prove a challenging undertaking. This review
      discusses the physiologic and non-physiologic basis for side effects with ACE
      inhibition.

PMID- 15249801
TI  - Emergency medicine in Spain.

PMID- 15249802
TI  - Manifesto for the creation of the specialization of emergency medicine in Spain.

PMID- 15249803
TI  - Emergency physicians and rapid sequence intubation: a survey of Scottish teaching
      hospitals.
AB  - OBJECTIVES: Emergency definitive airway management is a fundamental skill for
      physicians in the emergency department. The aim of this survey was to determine
      the perceived confidence in the assessment and control of the emergency airway,
      including rapid sequence intubation, among physicians in Scottish teaching
      hospital emergency departments. METHODS: A postal survey of senior and middle
      grade physicians in seven Scottish teaching hospital emergency departments.
      RESULTS: The response rate was 78% (47/60). A total of 98% of physicians rated
      their confidence at assessing the difficult airway as 'reasonable' to 'very
      high'; 79% were confident concerning their ability to administer drugs to
      facilitate emergency intubation; 47% had used drugs for emergency intubation
      within the month preceding the survey, and 72% had done so within the 6 months
      before the survey. Consultants were more confident than trainees, as were those
      possessing the Fellow of the Royal College of Anaesthetists qualification or a
      Diploma in Anaesthetics (UK). Those possessing the Fellowship of the Royal
      College of Anaesthetists qualification had all performed a rapid sequence
      intubation within the past month. CONCLUSION: Physicians in Scottish teaching
      hospital emergency departments have high levels of self-rated confidence in
      assessment and their ability to secure the emergency airway utilizing drugs to
      facilitate emergency intubation. Consultants and those with anaesthetic
      qualifications are more confident than trainees and those without such a
      qualification.

PMID- 15249804
TI  - Physician knowledge of herbal toxicities and adverse herb-drug interactions.
AB  - OBJECTIVE: To determine how knowledgeable physicians are regarding the toxic
      effects and drug interactions of herbal remedies. METHODS: An anonymous voluntary
      demographic survey and 16-question, multiple-choice quiz was distributed at
      educational meetings of emergency medicine and internal medicine physicians. The
      primary outcome measures were to determine whether significant associations
      existed between quiz scores and the amount of clinical experience, or between
      quiz scores and self-assessed familiarity with the topic of herbal toxicities and
      adverse herb-drug interactions. RESULTS: A total of 142 surveys and quizzes were
      completed by 59 attending physicians, 57 resident physicians, and 26 medical
      students. The mean subject score on the quiz was only slightly higher than would
      have occurred from random guessing. Neither the amount of the subjects' clinical
      experience, nor their self-assessed familiarity with herbal toxicities and drug
      interactions correlated significantly with the score on the quiz. CONCLUSION: The
      physicians and medical students surveyed had little training in herbal toxicities
      and drug interactions. They generally rated their familiarity with these topics
      as 'poor', and their scores on the quiz bore out this assessment as correct.
      Educational efforts might improve physician knowledge of the adverse effects of
      herbal remedies.

PMID- 15249805
TI  - Quality control programme for acute pain management in emergency medicine: a
      national survey.
AB  - OBJECTIVE: This national survey was carried out to evaluate the quality programme
      for acute pain management in the emergency department (ED) and in pre-hospital
      emergency medical services (EMS). METHODS: Two types of questionnaires were sent
      to the chief consultant and the chief nurse of all ED and EMS. Data collected
      were: the type of structure, quality programme organization, acute pain
      management, and the training needs to initiate a pain quality programme. RESULTS:
      A total of 363 questionnaires were recorded (198 from chief consultants) with 98%
      of questionnaires being usable. A pain management committee existed in 71% of
      cases, a quality committee in 83%. A complete quality control procedure existed
      in 53% of units. An audit on pain management was carried out in only 23% of
      cases. Training in quality was performed for 64% of physicians and 68% of nurses.
      Training specifically for pain management was carried out for physicians in 56%
      of cases and for nurses in 68% of cases. Pain therapeutics protocols existed in
      69% of cases. Pain intensity was evaluated 'systematically or often' in 64% at
      the beginning of patient management, and in 56% at the end of patient management.
      The staff was 'not very motivated' for a pain management quality programme in
      less than 3% of responses. A total of 61% of chief consultants and 58% of chief
      nurses requested advice. CONCLUSION: Most ED and EMS units seem to master the
      quality control programme methodology. Units are highly motivated to initiate a
      quality control programme on pain. Nevertheless, its implementation could benefit
      from some external support.

PMID- 15249806
TI  - X-ray requesting patterns before and after introduction of the Ottawa Knee Rules
      in a UK emergency department.
AB  - OBJECTIVES: To compare knee radiology requesting rates among junior doctors
      before and after the formal introduction of the Ottawa Knee Rules (OKR) in a UK
      emergency department (ED), and to test the validity of the OKR for decisions on
      the use of radiography for acute, isolated knee injuries. METHODS: All junior
      doctors in a district general hospital ED seeing adult patients with isolated
      knee injuries completed a questionnaire before and after the introduction of the
      OKR. All patients were followed up to obtain a final diagnosis. The outcome
      measures were: adherence to the OKR, the presence of a fracture and whether a
      radiograph had been requested. The results were analysed to determine the
      sensitivity, specificity, positive and negative predictive values of the OKR.
      Comparisons between the request rate for knee radiography before and after the
      introduction of the OKR were made. RESULTS: A total of 130 patients were enrolled
      and followed up over a 3-month period; 58 before and 72 after OKR introduction.
      The OKR had a sensitivity of 100% (71.8-100%), a specificity of 55.1% (46.1
      64.1%), a positive predictive value of 18.5% (9.03-27.9%) and a negative
      predictive value of 100% (87.8-100%) for the detection of bony injury. The
      introduction of the OKR did not result in a significant reduction in the number
      of radiographs performed (58.6-55.6%; P= 0.726). DISCUSSION: This study shows the
      OKR to be a highly sensitive clinical guide with a high negative predictive value
      in the setting of a UK ED. It suggests that the reduction in radiograph requests
      seen elsewhere may not be as apparent in this setting.

PMID- 15249807
TI  - Syncope in acute pulmonary embolism.
AB  - BACKGROUND: Syncope is a possible but little known presenting manifestation of
      acute pulmonary embolism (PE). The importance of syncope at the presentation of
      acute PE is not known. OBJECTIVES: To report the frequency and to establish the
      prognostic significance of syncope at the presentation of acute PE. METHODS: A
      retrospective review of the records of 154 consecutive patients admitted to an
      Internal Medicine service with acute PE. RESULTS: Fourteen patients with acute PE
      (9.1%) had syncope at presentation. Epidemiological and clinical characteristics
      (including respiratory failure, right heart failure and arterial hypotension),
      and hospital mortality were similar in patients with or without syncope.
      CONCLUSIONS: Syncope is not an uncommonly presenting manifestation of acute PE.
      Patients with acute PE and syncope have similar characteristics to those without
      syncope. Syncope does not seem to determine a poor prognosis.

PMID- 15249808
TI  - Effect of resuscitative mild hypothermia and oxygen concentration on the survival
      time during lethal uncontrolled haemorrhagic shock in mechanically ventilated
      rats.
AB  - OBJECTIVE: To test the hypothesis that resuscitative mild hypothermia (MH) (34
      degrees C) or breathing fractional inspired oxygen (FIo2) of 1.0 would prolong
      survival time during lethal uncontrolled haemorrhagic shock (UHS) in mechanically
      ventilated rats. METHODS: Forty Wistar rats were anaesthetized with halothane,
      nitrous oxide and oxygen (70/30%), intubated and mechanically ventilated. UHS was
      induced by volume-controlled blood withdrawal of 3 ml/100 g over 15 min, followed
      by 75% tail amputation of its length. The animals were randomly divided into four
      UHS treatment groups (10 rats in each group): group 1 was maintained on an FIo2
      of 0.21 and rectal temperature of 37.5 degrees C. Group 2 was maintained on an
      FIo2 of 0.21 and induced MH. Group 3 was maintained on an FIo2 of 1.0 and 37.5
      degrees C. Group 4 was maintained on an FIo2 of 1.0 and MH. Rats were observed
      otherwise untreated until death. RESULTS: During the initial blood withdrawal,
      mean arterial pressure (MAP) decreased to 40 mmHg, and the heart rate (HR)
      increased up to 400 beats/min. The induction of MH increased MAP to 60 mmHg and
      increased survival time. Moreover, it reduced the HR to 300 beats/min but did not
      increase bleeding. Ventilation with an FIo2 of 1.0 did not influence MAP, blood
      loss or survival time, but increased arterial oxygen tension. The mean survival
      time was 62, 202, 68 and 209 min in groups 1, 2, 3 and 4, respectively. Blood
      loss from the tail was 1.0, 1.2, 0.9 and 0.7 ml, respectively, in groups 1, 2, 3
      and 4. CONCLUSION: MH prolonged the survival time during UHS in mechanically
      ventilated rats. However, an FIo2 of 1.0 did not influence the survival time or
      blood loss from the tail.

PMID- 15249809
TI  - Isolated tracheal rupture caused by blunt trauma and the importance of early
      diagnosis: a case report.
AB  - Tracheal rupture usually occurs after blunt traumas. Isolated tracheal rupture is
      an extremely rare condition. The diagnosis of isolated tracheal rupture is very
      important for treatment and prognosis. Physical examination and imaging
      techniques should be used to make the diagnosis. Lateral neck and chest X-rays
      are very important for early diagnosis. Other techniques are thorax, neck
      tomography and bronchoscopy. In this paper we present a case of isolated tracheal
      rupture and discuss the early diagnostic techniques used.

PMID- 15249810
TI  - Femoral neck stress fracture in a sanitary worker.
AB  - Stress fractures of the femoral neck are uncommon, it is important to have a high
      index of suspicion in young active people who perform repetitive vigorous
      activity or have recently had an increase in frequency of such activity. We
      report a case of femoral neck stress fracture in a sanitary worker which was
      treated successfully with a dynamic hip screw.

PMID- 15249811
TI  - A human bite to the scrotum: a case report and review of the literature.
AB  - Human bites to the scrotum are rare and can be associated with a high morbidity
      rate if poorly managed. We report a case of a human bite to the scrotum that was
      successfully treated with a 5-day course of antibiotics, surgical debridement and
      healing by secondary intention.

PMID- 15249812
TI  - A case of breathlessness, confusion and diarrhoea.
AB  - A 61-year-old woman presented to the emergency department with acute-onset
      breathlessness, fever, sore throat and confusion. Her initial investigations
      revealed hyponatremia and middle lobe consolidation. In view of the atypical
      symptoms and signs, erythromycin was commenced. Urinary legionella antigen was
      requested and that tested positive. She was one of the first few patients whose
      findings alerted us to a possible outbreak of legionnaire' disease. We drew the
      following conclusions from our experience with this and other cases that we saw
      during the legionnaires' outbreak: an atypical presentation is common, as seen in
      this lady with confusion. If two cases of atypical pneumonias test positive for
      legionella within a period of a week, we suggest that public health authorities
      should be notified to identify the source and contain it. There is a need for
      continuous and high vigilance for legionnaires' disease.

PMID- 15249813
TI  - Lemierre's syndrome: how a sore throat can end in disaster.
AB  - Lemierre's syndrome is characterised by a history of recent oropharyngeal
      infection, clinical or radiological evidence of internal jugular vein
      thrombophlebitis and isolation of an anaerobic pathogen. We present a case report
      and review the literature.

PMID- 15249814
TI  - Spontaneous oesophageal perforation as a complication of vomiting in
      gastroenteritis -- case report.
AB  - This is a case report of oesophageal perforation as the complication of a
      commonly encountered benign disease -- gastroenteritis. A 68-year-old man first
      presented to the Emergency Department complaining of watery diarrhoea. He was
      treated and discharged. He re-attended 5 h later complaining of epigastric pain
      radiating to his back, vomiting bloodstained fluid and persistent watery
      diarrhoea. Again, he was treated and discharged. He re-attended 3 days later
      complaining of anorexia, cough, dyspnoea and right-sided chest pain radiating to
      his back, and subjective weight loss in the previous few days. Chest X-ray
      revealed right pleural effusion, pneumomediastinum and subcutaneous emphysema in
      the supraclavicular fossae. Computed chest tomogram and water-soluble contrast
      swallow confirmed 'spontaneous' oesophageal perforation. Although rare, this
      entity must be considered in any acutely ill patient complaining of respiratory
      and gastrointestinal symptoms, especially after recent vomiting.

PMID- 15249815
TI  - The importance of clinical suspicion in diagnosing pulmonary embolism: a case of
      false-positive high probability radionuclide perfusion lung scan.
AB  - The accuracy of scintigraphic evidence of perfusion defects, even when classified
      as 'high probability' by matching with ventilation techniques or thoracic
      roentenograms is unsatisfactory when used without a pre-test clinical evaluation
      of probability. Although unusual, a complete or near-complete unilateral absence
      of perfusion in a lung with normal perfusion controlaterally must alert
      clinicians to the possibility of a false-positive result. In such instances, the
      administration of therapeutic dosages of fibrinolitic and antithrombotic agents
      (or even surgery) may lead to deleterious consequences. We report a patient with
      malignancy causing extrinsic narrowing of the pulmonary artery leading to a
      drastic impairment in the perfusion of an entire lung, compatible with, but not
      diagnostic of massive pulmonary embolism.

PMID- 15249816
TI  - The paradox of hypotension and pheochromocytoma: a case report.
AB  - Pheochromocytomas produce, store and secrete catecholamines. Diagnosis is often
      suspected in young patients with severe hypertension. We present the case of a 47
      year-old woman without a previous history of hypertension, whose initial
      presentation was cardiovascular shock. Despite early diagnosis of the disease,
      the fulminant evolution of the pheochromocytoma crisis was fatal a few hours
      after admission. Only a few therapeutic options remain when haemodynamic collapse
      is catecholamine induced.

PMID- 15249817
TI  - Acute nutmeg poisoning.
AB  - We present a case of acute nutmeg poisoning in a 16-year-old youth who had
      ingested the substance for recreational purposes. He developed a number of
      neurological symptoms and signs along with non-specific electrocardiographic
      changes and anti-cholinergic-type symptoms. We describe the pharmacology of
      nutmeg and its constituents, discuss its metabolism, and make recommendations
      about the management of nutmeg poisoning. Emergency staff should be aware of the
      effects of nutmeg, which may present in marijuana users who seek alternative
      substances.

PMID- 15249818
TI  - Homeopathic products, not as innocent and safe as they seem? A case report.
AB  - Although homeopathic and other alternative products are very popular and are
      supposed to be safe and harmless they are not free of risks. We present the case
      of a 29-year-old woman who had to be treated for a state of extreme agitation
      after using speed, alcohol and homeopathic slimming droplets (LOCO X112).
      Toxicological analysis of these droplets revealed the presence of thyroid extract
      and diethylpropione, an amphetamine-like noradrenergic anorectic agent banned in
      Belgium. This case among other reports in the literature proves that homeopathic
      products are not as safe and harmless as they seem. Medical professionals as well
      as the public should be aware of this.

PMID- 15249819
TI  - Response to 'Universal screening for interpersonal violence: inability to prove
      universal screening improves provision of service' by Datner et al.

PMID- 15249820
TI  - Bone scintigraphy in acetabular labral tears.
AB  - BACKGROUND: Acetabular labral tears are an increasingly recognized cause of hip
      pain in young adults with hip dysplasia and older patients with degenerative
      disease of the hips. METHODS: The authors analyzed retrospectively bone
      scintigraphy in 27 patients with acetabular labral tears diagnosed by
      MRI/arthroscopy. Analysis was also made of scintigraphy in 30 patients without
      labral tears being investigated for other causes of hip pain for comparison.
      RESULTS: Patients with labral tears had hyperemia of the superior or superomedial
      aspect of the acetabulum and increased delayed uptake in either a focal superior
      pattern or in an "eyebrow" pattern of a superomedial tear. This pattern was not
      seen in any other sources of hip pathology. CONCLUSION: Uptake in the superior or
      superomedial aspect of the acetabular rim is characteristic of a labral tear.
      Absence of this pattern carries a high negative predictive value for the
      diagnosis.

PMID- 15249821
TI  - Evaluation of a 3-hour indium-111 leukocyte image as a surrogate for a technetium
      99m nanocolloid marrow scan in the diagnosis of orthopedic infection.
AB  - OBJECTIVES: This is a retrospective study to evaluate a 3-hour In-111-labeled
      leukocyte image as a surrogate for a Tc-99m nanocolloid marrow scan in the
      investigation of suspected orthopedic infection using In-111 leukocyte
      scintigraphy. METHODS: Images from 51 patients who had received contemporaneous
      In-111-labeled leukocyte scintigraphy and Tc-99m nanocolloid marrow scintigraphy
      were reviewed. Initially, the 3-hour and 22-hour In-111-labeled leukocyte images
      were compared. Sites of abnormal uptake on the 22-hour image were correlated with
      the 3-hour image and were graded according to the level of concordance or
      discordance. One week later, the Tc-99m nanocolloid images and 22-hour In-111
      labeled leukocyte images of the same patients were compared and graded for
      concordance or discordance. When discrepancies in grading arose between the
      observers, a consensus opinion was achieved after additional review of the images
      a week later. RESULTS: On inspection of the 22-hour In-111 leukocyte images, 93
      sites of focal, potentially abnormal leukocyte accumulation were identified. When
      the grading system was reduced to simply "concordant" or "discordant," there was
      good agreement between the observers in the majority of cases, with kappa
      statistics 0.77 for Tc-99m nanocolloid versus 22-hour In-111-labeled leukocyte
      images and 0.78 for 3-hour versus 22-hour In-111-labeled leukocyte images. Using
      the comparison of the Tc-99m nanocolloid marrow scan and the 22-hour In-111
      labeled leukocyte images to identify concordance or discordance as the "gold
      standard" for scintigraphic evaluation of suspected orthopedic infection,
      comparison of the 3-hour In-111-labeled leukocyte images with the 3-hour In-111
      labeled leukocyte images gave a sensitivity of 77%, a specificity of 77%, and an
      accuracy of 77%. CONCLUSIONS: A 3-hour image is helpful using In-111-labeled
      leukocyte scintigraphy.

PMID- 15249822
TI  - Acute bilateral basal ganglia lesions in patients with diabetic uremia: an FDG
      PET study.
AB  - PURPOSE: Head CT and MRI show characteristic changes in the syndrome of acute
      bilateral basal ganglia lesions in patients with diabetic uremia. However, they
      do not provide further insight into the underlying pathophysiology. To further
      clarify the biologic mechanism of the syndrome, F-18 fluorodeoxyglucose (FDG)
      positron emission tomography (PET) was used in 2 patients. METHODS: PET studies
      were performed in 2 diabetic uremic patients with acute movement disorders. The
      cerebral glucose metabolic rates in these 2 patients were compared with 11 normal
      age-matched controls. The images were further analyzed with statistical
      parametric mapping to identify regions of significant metabolic abnormality.
      RESULTS: The cases showed markedly reduced glucose metabolism in the bilateral
      basal ganglia, especially in the bilateral putamens, where the glucose uptake was
      nearly absent. CONCLUSIONS: FDG-PET correlates better with the clinical
      conditions and provides more pathophysiological information than head CT or MRI
      scans in bilateral basal ganglia lesions in patients with diabetic uremia. We
      propose that acute exacerbation of a long-term glucose utilization failure in the
      basal ganglia cells produced these lesions.

PMID- 15249823
TI  - Interobserver reproducibility in the interpretation of captopril renograms from
      patients suspected of having renovascular hypertension.
AB  - This work was undertaken to identify, in hypertensive patients suspected of
      having renovascular hypertension (RVH), scintigraphic images and curves whose
      interpretation could be difficult. The baseline and postcaptopril Tc-99m MAG 3
      images and curves from 10 patients clinically suspected of having RVH were
      retrospectively selected to have a wide sample of images and curves. The data and
      a multiple-choice questionnaire were presented as a PowerPoint file, which was
      sent electronically to Belgian nuclear medicine physicians; they had to answer if
      the images and curves were or were not suggestive of the diagnosis of RVH or if
      it was impossible to answer. There was near-complete interobserver agreement for
      normal baseline and postcaptopril data, for unilateral postcaptopril delayed
      transit and/or impaired uptake. Agreement was not as good for bilateral and
      symmetrical changes, for mild changes, or in cases of impaired function. This
      study shows that the analysis by the Internet of interobserver agreement is an
      easy and rapid method allowing one to identify difficult to interpret pre- and
      postcaptopril renographic data.

PMID- 15249824
TI  - Tc-99m DMSA uptake by metastatic colorectal carcinoma.
AB  - Extrarenal uptake of Tc-99m DMSA is not seen very often. It has previously been
      described in metastatic disease and was mainly attributed to the presence of V
      DMSA in the injected solution. We report a clinical case of incidental
      visualization of metastatic bone disease of the colon in a patient with renal
      failure. This could be the result of not only the presence of V-DMSA, but also
      the renal failure and the atypia of the lesions.

PMID- 15249825
TI  - Large renal cell carcinoma isometabolic with normal liver on F-18 FDG PET scan.
AB  - Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is a very
      effective imaging modality in the diagnosis, staging, and monitoring of a variety
      of malignant conditions. The principle of imaging is based on the enhanced
      utilization of glucose by cancer. In this report, we describe a patient with
      renal cell carcinoma who showed FDG uptake isometabolic to normal liver.

PMID- 15249826
TI  - Superior vena cava obstruction with intrahepatic and systemic-pulmonary venous
      right-to-left shunts.

PMID- 15249827
TI  - Incidental bronchogenic cyst detected on F-18 FDG positron emission tomography.

PMID- 15249828
TI  - Chronic cholecystitis detected by FDG-PET.

PMID- 15249829
TI  - Diagnostic I-123 scintigraphy to assess potential breast uptake of I-131 before
      radioiodine therapy in a postpartum woman with thyroid cancer.

PMID- 15249830
TI  - Small cell carcinoma of the parotid gland: evaluation with FDG PET imaging.

PMID- 15249831
TI  - Unusual uptake on gallium-67 imaging in organizing pneumonia.

PMID- 15249832
TI  - Tuberculosis of calcaneus: assessing treatment response by Tc-99m MDP
      scintigraphy.

PMID- 15249833
TI  - Multicentric skeletal tuberculosis in the absence of pulmonary disease.

PMID- 15249834
TI  - Bone imaging in "giant" giant cell tumor.

PMID- 15249835
TI  - Bull rider's myositis.

PMID- 15249836
TI  - The saddle sign: bilateral thigh adductor compartment uptake of Tc-99m MDP.

PMID- 15249837
TI  - Massive bladder diverticuli demonstrated on skeletal scintigraphy.

PMID- 15249838
TI  - Bone scan findings in idiopathic hyperphosphatasia.

PMID- 15249839
TI  - Enhanced liver uptake of Tc-99m-labeled RBCs during gastrointestinal bleed
      scintigraphy using transfused RBCs compared with autologous RBCs.

PMID- 15249840
TI  - Current readings in nuclear medicine.

PMID- 15249842
TI  - Long-term treatment of Alzheimer disease: efficacy and safety of
      acetylcholinesterase inhibitors.
AB  - During the past 20 years, research on Alzheimer disease (AD) and other dementias
      has increased our understanding of these disorders and has opened doors to new
      methods of treatment. Acetylcholinesterase inhibitors (AChEIs) have been
      successful in reducing symptoms in patients with mild-to-moderate AD and led to
      the US Food and Drug Administration's approval of four AChEIs for the treatment
      of AD. Although these agents are approved for only mild-to-moderate AD, and the
      available data for most of them are from trials of only 6 months' duration, long
      term studies suggest that the benefits of AChEI treatment can endure for up to 4
      years. A common pattern of response to treatment is initial improvement in
      cognition, followed by maintenance of cognitive gains above baseline for up to 1
      year. Generally there is a decline in cognition to below baseline levels after
      approximately 1 year of treatment, but the level of cognition remains above that
      predicted for those not receiving pharmacologic treatment. Furthermore, long-term
      studies suggest that early diagnosis and treatment with AChEIs yield better long
      term outcomes. Patients who received continuous pharmacologic treatment from the
      outset generally had better long-term outcomes than those who received placebo in
      the double-blind phase of these trials.

PMID- 15249844
TI  - The needs of the caregiver in the long-term treatment of Alzheimer disease.
AB  - The long-term well-being of caregivers should be included as part of the
      treatment of patients with Alzheimer disease (AD). Throughout the process of
      caring for patients with AD, caregivers frequently experience social, emotional,
      physical, and financial losses, which become more significant as the disease
      progresses. Minimizing these losses is a goal in the overall management of AD.
      Successful treatment of the patient has been shown to positively impact quality
      of life for the caregiver. Randomized, controlled studies of acetylcholinesterase
      inhibitors (AChEIs) have demonstrated the effectiveness of these agents in
      stabilizing cognitive function and delaying behavioral symptoms. Moreover, a
      decrease in the incidence of nursing home placement has been associated with this
      therapy. The growing burden of AD on families and society as a whole warrants the
      investigation of ways to minimize the impact of AD. AChEIs play an important role
      in this effort. Further studies are needed to more closely examine the impact of
      specific AChEIs on caregiver burden.

PMID- 15249843
TI  - Noncognitive symptoms and long-term treatment expectations for Alzheimer disease.
AB  - Alzheimer disease (AD) is characterized by both cognitive and noncognitive
      symptoms that can lead to functional impairment, increased caregiver burden, and
      institutionalization. Pharmacologic therapies traditionally used to treat
      cognitive symptoms of AD may prevent and/or control many noncognitive symptoms as
      well. The acetylcholinesterase inhibitors (AChEIs) galantamine, rivastigmine, and
      donepezil have been shown to maintain or improve function for at least 1 year.
      They also have been shown to improve or delay the onset of neuropsychiatric and
      behavioral symptoms. These noncognitive benefits can impact greatly the lives of
      patients with AD as well as the persons who care for them.

PMID- 15249845
TI  - The economic benefits of acetylcholinesterase inhibitors for patients with
      Alzheimer disease and associated dementias.
AB  - Most cost-effectiveness studies using simulation modeling have demonstrated that
      donepezil, rivastigmine, and galantamine are cost effective for the treatment of
      mild-to-moderate Alzheimer disease (AD). These conclusions are in large part
      based on the assumption that improvement in cognitive status, or prevention of
      cognitive and functional decline, reduces the amount of time patients spend
      institutionalized or receiving other full-time care. However, as discussed in
      this article, outcomes besides delay to institutionalization affect the costs of
      AD. In reviews of utilization data from Medicare and managed care organizations,
      it was noted that hospitalization and post acute care in skilled nursing
      facilities accounted for the largest amount of excess direct costs, even among
      patients with mild or moderate AD. These utilization reviews also suggest that
      many patients with AD and related dementias require inpatient care because they
      are not able to self-manage comorbid conditions. The improvements in cognitive
      status and daily functioning associated with acetylcholinesterase inhibitor
      (AChEI) therapy are expected to translate into improved management of
      comorbidities and reduced caregiver burden, thus reducing the total cost of care.
      To confirm these and other economic benefits of AChEIs, pharmacoeconomic outcomes
      should be evaluated routinely as part of randomized, controlled trials and
      through well-controlled observational studies of AD patients in community and
      institutional settings.

PMID- 15249846
TI  - The predementia diagnosis of Alzheimer disease.

PMID- 15249847
TI  - Exercise, aging, and Alzheimer disease.

PMID- 15249848
TI  - Exercise level and cognitive decline: the MoVIES project.
AB  - Growing evidence suggests that physical exercise may be protective against
      cognitive impairment and decline. A prospective study of a representative rural
      community sample (N = 1,146) aged 65+ years examined self-reported exercise
      habits and measured global cognitive function using the Mini-Mental State
      Examination (MMSE). A composite variable "exercise level" combining type,
      frequency, and duration of exercise was created with three levels: "high
      exercise" (aerobic exercise of > or = 30 minute duration > or = 3 times a week),
      "low exercise" (all other exercise groups), and "no exercise." Cognitive decline
      was defined as being in the 90 percentile of decline in this cohort, ie,
      declining by 3 or more MMSE points during the 2-year interval between two
      assessments. In a multiple regression model, high exercise level at the baseline
      assessment was negatively associated with, ie, was protective against, being in
      the group with the greatest amount of decline at the follow-up assessment, after
      adjusting for likely confounders (odds ratio = 0.39; 95% confidence interval,
      0.19, 0.78). When high exercise was redefined using frequency as > or = 5 days
      per week as the threshold, as per the Surgeon General's guidelines, both low
      exercise and high exercise were negatively associated with cognitive decline.
      Exercise may have implications for prevention of cognitive decline.

PMID- 15249849
TI  - Early-onset Alzheimer disease: when is genetic testing appropriate?
AB  - Alzheimer disease (AD) is a neurodegenerative disease that is currently not
      preventable or curable. Early-onset AD can be due to mutations in several
      autosomal dominant genes. Clinical testing is available for presenilin 1 (PS1),
      which is the most common of these genes. However, many practical and ethical
      issues must be considered before ordering this test for patients with early-onset
      AD. In this paper, we present a case that demonstrates the complexities of
      genetic testing for early-onset AD.

PMID- 15249850
TI  - The validity and reliability of chinese frontal assessment battery in evaluating
      executive dysfunction among Chinese patients with small subcortical infarct.
AB  - OBJECTIVES: Frontal Assessment Battery (FAB) is a valid and reliable screening
      test for evaluating executive dysfunction among whites with frontal and
      subcortical degenerative lesions. We studied the properties of a Chinese version
      of FAB (CFAB) in evaluating executive dysfunction among Chinese stroke patients
      with small subcortical infarct. METHODS: Concurrent validity was evaluated using
      Wisconsin Card Sorting Tst (WCST) and Mattis Dementia Rating Scale
      Initiation/Perseveration Subset (MDRS I/P) among 41 controls and 30 stroke
      patients with small subcortical infarct. Discriminant validities of CFAB and its
      subitems were compared with those of Mini-Mental State Examination (MMSE).
      Internal consistency, test-retest, and interrater reliability of CFAB were
      evaluated. RESULTS: The CFAB had low to good correlation with various executive
      measures: MDRS I/P (r = 0.63, p < 0.001), number of category completed (r = 0.45,
      p < 0.001), and number of perseverative errors (r = -0.37, p < 0.01) of WCST.
      Among the executive measures, only number of category completed had significant
      but small contribution (6.5%, p = 0.001) to the variance of CFAB. A short version
      of CFAB using three items yielded higher overall classification accuracy (86.6%)
      than that of CFAB full version (80.6%) and MMSE (77.6%). Internal consistency
      (alpha = 0.77), test-retest reliability (rho = 0.89, p < 0.001), and interrater
      reliability (rho = 0.85, p < 0.001) of CFAB were good. CONCLUSION: Although CFAB
      is reliable, it is only moderately valid in evaluating executive dysfunction
      among Chinese stroke patients with small subcortical infarct. The clinical use of
      CFAB in the evaluation of executive dysfunction among this group of patients
      cannot be recommended at this stage.

PMID- 15249851
TI  - The effect of a structured intervention on caregivers of patients with dementia
      and problem behaviors: a randomized controlled pilot study.
AB  - The objective was to assess the effect of a structured intervention on caregiver
      stress and the institutionalization rate of patients with dementia and problem
      behaviors. Caregivers contacting the Federazione Alzheimer Italia (AI) to receive
      help, advice, or information in relation to problem behaviors of outpatients were
      enrolled. Eligible caregiver-patient dyads were randomized to receive either a
      structured intervention or the counseling AI usually provides (control group).
      After basal assessment, families were reassessed at 6 and 12 months. Problem
      behavior (particularly agitation) was the only variable significantly correlated
      (P = 0.006) with the baseline caregivers' stress score. Thirty-nine families
      completed the 12-month follow-up; the mean problem behavior score was
      significantly lower in the intervention than the control group (p < 0.03); the
      time needed for care of the patient increased by 0.5 +/- 9.7 hours/day in the
      control group and decreased by 0.3 +/- 4.1 in the intervention group (p = 0.4,
      Wilcoxon test). The main determinant of institutionalization seemed to be the
      level of caregiver stress (p = 0.03). In patients of the intervention group,
      there was a significant reduction in the frequency of delusions. This pilot study
      suggests that caregiver stress is relieved by a structured intervention. The
      number of families lost to follow-up, the relatively short duration of the study,
      and the ceiling effect due to the severity of the clinical characteristics of
      patients probably all partly dilute the observed findings.

PMID- 15249852
TI  - Predicting nursing home admission: estimates from a 7-year follow-up of a
      nationally representative sample of older Americans.
AB  - This study determines whether prevalence and predictors of nursing home admission
      changed in the 1990s, during a period of dramatic changes in the service
      provision for and medical care of chronic impairments. Data from the 1993-2000
      surveys of the Asset and Health Dynamics Among the Oldest Old (AHEAD) Study, a
      longitudinal and nationally representative sample, were used. Proportional hazard
      models were used to determine the effects of dementia, physical functioning,
      clinical conditions, and sociodemographics on the likelihood of nursing home
      admission. Of the 6,676 respondents, 17% were admitted to a nursing home. Models
      excluding functional impairment demonstrated significant effects of chronic
      medical conditions and dementia on the risk of institutionalization. After
      controlling for functional impairment, dementia still had significant and strong
      effects on institutionalization but clinical conditions did not, suggesting that
      the impact of dementia goes beyond its effect on physical functioning. Nursing
      home admissions did not decrease during the study period, and the impact of
      dementia on the risk of nursing home admission did not decrease. Interventions
      for individuals with dementia should impact the behavioral aspects of the
      condition and slow disease progression in addition to improving physical
      functioning.

PMID- 15249853
TI  - Out-of-pocket health care expenditures among older Americans with dementia.
AB  - The number of older individuals with dementia will likely increase significantly
      in the next decades, but there is currently limited information regarding the out
      of-pocket expenditures (OOPE) for medical care made by cognitively impaired
      individuals and their families. We used data from the 1993 and 1995 Asset and
      Health Dynamics Study, a nationally representative longitudinal survey of older
      Americans, to determine the OOPE for individuals with and without dementia.
      Dementia was identified in 1993 using a modified version of the Telephone
      Interview for Cognitive Status for self-respondents, and proxy assessment of
      memory and judgment for proxy respondents. In 1995, respondents reported OOPE
      over the prior 2 years for: 1) hospital and nursing home stays, 2) outpatient
      services, 3) home care, and 4) prescription medications. The adjusted mean annual
      OOPE was 1,350 US dollars for those without dementia, 2,150 US dollars for those
      with mild/moderate dementia, and 3,010 US dollars for those with severe dementia
      (p < 0.01). Expenditures for hospital/nursing home care (1,770 per year US
      dollars) and prescription medications (800 per year US dollars) were the largest
      OOPE components for those with severe dementia. We conclude that dementia is
      independently associated with significantly higher OOPE for medical care compared
      with those with normal cognitive function. Severe dementia is associated with a
      doubling of OOPE, mainly due to higher payments for long-term care. Given that
      the number of older Americans with dementia will likely increase significantly in
      the coming decades, changes in public funding aimed at reducing OOPE for both
      long-term care and prescription medications would have considerable impact on
      individuals with dementia and their families.

PMID- 15249854
TI  - A multinational review of recent trends and reports in dementia caregiver burden.
AB  - This systematic review of the literature focuses on the influence of ethnic,
      cultural, and geographic factors on the caregivers of patients with dementia. In
      particular, we explore the impact of cultural expectations on five important
      questions: 1) Do the characteristics of dementia affect caregiver burden? 2) Do
      characteristics of the caregiver independently predict burden? 3) Does the
      caregiver affect patient outcomes? 4) Does support or intervention for caregiver
      result in reduced caregiver burden or improved patient outcomes? 5) Finally, do
      patient interventions result in reduced caregiver burden or improved patient
      outcomes? Our findings suggest that noncognitive, behavioral disturbances of
      patients with dementia result in increased caregiver burden and that female
      caregivers bear a particularly heavy burden across cultures, particularly in
      Asian societies. Caregiver burden influences time to medical presentation of
      patients with dementia, patient condition at presentation, and patient
      institutionalization. Moreover, interventions designed to reduce caregiver burden
      have been largely, although not universally, unsuccessful. Pharmacological
      treatments for symptoms of dementia were found to be beneficial in reducing
      caregiver burden. The consistency of findings across studies, geographic regions,
      cultural differences, and heathcare delivery systems is striking. Yet, there are
      critical differences in cultural expectations and social resources. Future
      interventions to reduce caregiver burden must consider these differences,
      identify patients and caregivers at greatest risk, and develop targeted programs
      that combine aspects of a number of interventional strategies.

PMID- 15249855
TI  - Differential expression of HMGA1 and HMGA2 in dermatofibroma and
      dermatofibrosarcoma protuberans: potential diagnostic applications, and
      comparison with histologic findings, CD34, and factor XIIIa immunoreactivity.
AB  - The histologic distinction of dermatofibrosarcoma protuberans (DFSP) and
      dermatofibroma (DF) may be difficult, especially in the case of DF extending into
      the subcutaneous fat (deep DF). CD34 and Factor XIIIa staining is commonly used
      in separating DF from DFSP, but is not always helpful. HMGA1 and HMGA2 genes,
      members of the high mobility group protein family genes, encode proteins that act
      as architectural transcription factors and are frequently dysregulated in a
      variety of benign or locally aggressive mesenchymal tumors. In this study, we
      evaluated the immunoreactivity of HMGA1 and HMGA2 in a series of DF and DFSP to
      determine the possible utility for these markers in the differential diagnosis of
      these two entities. Immunohistochemical stains were performed on paraffin
      embedded tissues from 22 cases of DF, including 14 cases of deep DF and 14 cases
      of DFSP, using antibodies against HMGA1 and HMGA2. CD34 and Factor XIIIa
      immunoreactivity was also evaluated in these lesions and compared with the
      results of HMGA immunostaining. Immunopositivity for both HMGA1 and HMGA2 was
      seen in 21of 22 (96%) DFs, but in only 3 (21%) and 1 (7%) of 14 DFSPs,
      respectively. While 100% of DFSP stained for CD34, 36% of DF also labeled for
      CD34. The immunoreactivity of HMGA1 and HMGA2 in DF was generally strong and
      diffuse, in contrast to weak and focal staining seen in DFSP. The proportion of
      cases with positive immunoreactivity for both markers was significantly higher in
      DF and in deep DF than in DFSP (P < 0.001). We conclude that HMGA1 and HMGA2
      expression can be used to distinguish DF from DFSP with a degree of accuracy that
      is fully equivalent to that of Factor XIIIa and CD34.

PMID- 15249856
TI  - Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of
      five cases.
AB  - Dermal clear cell tumors are not common. This group of lesions is comprised
      primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and
      metastatic clear cell carcinomas. We report the clinicopathologic features of
      five cases of a novel dermal clear cell neoplasm that appears mesenchymal in
      nature. The affected patients included 3 men and 2 women ranging in age from 38
      to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically
      described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest
      dimension and the lesions were present from weeks to 5 years prior to excision.
      Situated in the reticular dermis, the tumors usually extended to involve the
      subcutis with sparing of the papillary dermis. The tumors were composed of large
      optically clear cells with vesicular nuclei. The lesions entrapped adnexal
      structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25
      hpf). A single case showed more pleomorphic nuclei as well as quite frequent
      mitoses and was considered of uncertain biologic potential. Immunohistochemistry
      revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin
      (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly
      negative. All five lesions were locally excised; the more pleomorphic and
      mitotically active lesion was widely re-excised and given subsequent radiation
      therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of
      these lesions has recurred. These tumors appear to be mesenchymal in nature, but
      their precise line of differentiation is unknown. Recognition of these lesions is
      important to avoid confusion with better-known malignant neoplasms.

PMID- 15249857
TI  - Histopathology of cutaneous amebiasis.
AB  - Cutaneous amebiasis (CA) is the manifestation in the skin and underlying soft
      tissues of the pathogenic properties of Entamoeba histolytica, which may be the
      only expression of the infection or may be associated with disease in other
      organs. So far, there have been only isolated case reports on this disease. We
      herein report the histopathologic findings on a series of seven cases, six adults
      and one child, of CA. The most common findings include ulcers, areas of necrosis,
      mixed inflammatory infiltrates, and the presence of trophozoites, the invasive
      form of the parasite. CA is a very rare and severe disease, it is progressive and
      destructive; erythrophagocytosis, a microscopic sign of pathogenicity, is always
      seen in CA.

PMID- 15249858
TI  - Acral lentiginous melanoma in situ: a study of nine cases.
AB  - An acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma
      in Asians. However, it is unusual to encounter a patient showing only the
      histologic features of an ALM in situ. Here we describe clinical and histologic
      features of nine cases of ALM in situ including immunohistochemical staining with
      anti-S100 protein and HMB-45. All the patients had a long clinical history.
      Clinically, the lesions were characterized by a longitudinal pigmented streak in
      the nail plates, black pigmentation on the proximal or lateral nail fold, and an
      irregular border and variegated pigmentation on the sole or thumb. Total
      resections of the lesions were performed in all patients. All lesions, in both
      biopsy and excisional specimens demonstrated more melanocytes generally located
      in the basal layer of the epidermis. There was no dermal invasion. No recurrence
      of the disease had occurred in any patient after a follow-up period of between 6
      months to 12 years after surgery. These results suggest that ALM can evolve
      slowly over many years.

PMID- 15249859
TI  - Melanoma with prominent pigment synthesis (animal-type melanoma): a case report
      with ultrastructural studies.
AB  - Melanoma with prominent pigment synthesis or animal-type melanoma (ATM) is a very
      rare type of melanoma. Its histogenesis has not been elucidated and
      ultrastructural features have not been described in human beings. We present an
      additional case of ATM in a 28-year-old woman with positive sentinel node biopsy
      and provide the results of electron microscopic studies. Histopathologically, the
      skin lesion was composed of heavily pigmented neoplastic cells mostly arranged as
      large sheets, focally also in a nodular growth pattern. After bleaching, the
      neoplastic cells demonstrated round nuclei with 1 or rarely 2 conspicuous
      nucleoli and a prominent nuclear membrane and abundant, gray, slate-like
      cytoplasm. Some cells demonstrated round cytoplasmic inclusions. There was no
      nuclear pleomorphism, and only a few mitotic figures could be found after
      extensive search. Multiple areas of necrosis en masse of tumor cells were seen.
      The lymph node biopsy revealed a complete effacement of the lymph node
      architecture by the extensive proliferation of hyperpigmented cells in the
      parenchyma. Immunohistochemically, the same pattern of staining was seen on the
      bleached and unbleached slides both in the skin and in the lymph node. The
      neoplastic cells stained positively with MiTF (nuclei), NSE, NKI/C3, tyrosinase
      (weak), p53, and CD68. S-100 protein, HMB45, Melan A, Mac367, and lysozyme
      reacted negatively. Occasional cells (<1%) reacted with MIB-1. Ultra-structural
      studies revealed that the neoplastic cells possessed a large, indented nucleus
      with a prominent nuclear membrane, a single (para) centrally located nucleolus,
      and peripherally marginated chromatin. The cytoplasm was abundant and contained
      numerous single melanosomes and rare compound melanosomes. The melanosomes were
      in stages II to IV of maturation, with a marked predominance of stage II and
      stage III melanosomes. There was a high number of aberrant melanosomes with a
      wide variety of configurations. Melanophages were a minor component of the
      lesion. Our ultrastructural studies provide unequivocal evidence that ATM is a
      neoplasm of melanosome-producing cells. We also review the literature on ATM.

PMID- 15249860
TI  - Basal cell carcinoma with sebaceous differentiation.
AB  - Some authors have used sebaceous epithelioma as a synonym for basal cell
      carcinoma (BCC) with sebaceous differentiation. However, our review of the
      literature revealed that definite cases of BCC with sebaceous differentiation
      that provide adequate clinical and histopathologic information are scarce. We
      present the case of a 72-year-old woman with a pigmented nodular lesion on her
      right ala nasi region, clinically diagnosed as pigmented BCC.
      Histopathologically, this nodular lesion, which was completely excised, showed
      typical features of BCC. It was noteworthy that within one aggregation of the
      presented BCC, tiny and small duct-like structures lined by cornified layers with
      a crenulated inner surface were seen. Vacuolated cells were scattered within a
      few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The
      vacuolated cells were immunohistochemically positive for epithelial membrane
      antigen (EMA). These histopathologic findings demonstrated unquestionable
      sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation,
      which should be distinguishable from both sebaceoma and sebaceous carcinoma. The
      small duct-like structures lined by eosinophilic cuticle, indicating apocrine
      differentiation, were also observed in this BCC.

PMID- 15249861
TI  - Low-grade trichoblastic carcinosarcoma of the skin.
AB  - We present an unusual case of cutaneous carcinosarcoma with the epithelial
      component closely resembling nodular basal cell carcinoma, and the mesenchymal
      component composed of cells constituting extended follicular papillae. A solitary
      tumor was excised in an 80-year-old man. Histologic sections revealed an
      ulcerated, asymmetric, poorly circumscribed neoplasm composed of epithelial cells
      arranged in lobules with peripheral palisading or in a cribriform pattern. The
      epithelial cells were darkly basophilic with scant cytoplasm and round or oval
      nuclei with an indistinct chromatin pattern and nucleoli. Nuclei crowding and
      mitotic figures were observed. Some lobules contained melanin. There were no
      shadow cells, sebaceous or apocrine glandular differentiation. Each epithelial
      nodule was surrounded by multiple rows of cells with pale vesicular nuclei and
      scant cytoplasm. Smaller epithelial aggregations were encircled by these cells
      concentrically; in larger ones these cells were aligned across a broad front
      resembling so-called "continuous papillae". Additionally, numerous small
      follicular germ-like structures associated with papillae were seen. The cells
      composing "continuous papillae" showed nuclear pleomorphism, numerous mitotic
      figures including atypical ones, and nuclear crowding. At foci, the transition
      from the multilayered arrangement of these cells into their diffuse proliferation
      in the stroma was seen. There were no transitions between the epithelial and
      stromal component; both were intermingled as though being mutually dependent,
      with no areas revealing a high-grade tumor or dedifferentiation.
      Immunohistochemically, the epithelial cell component stained with cytokeratins.
      The cells of the mesenchymal component tested positive for vimentin and negative
      for desmin and cytokeratins. The proliferation index (Ki-67) was high in both
      components. There were also a high number of p53-positive cells in both
      compartments. We propose the term "low-grade trichoblastic carcinosarcoma" for
      this neoplasm. We are not aware of a similar tumor published in the English
      literature.

PMID- 15249862
TI  - "Atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's
      nevus: a critique in historical perspective of three concepts flawed fatally.
AB  - Our purpose in undertaking this Arbeit was to review all articles published about
      "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's
      nevus, to criticize them in a fashion that illuminates, and to come to
      conclusions compellingly about those subjects. We found that an overwhelming
      majority of neoplasms that claimed to be "atypical Spitz's nevus," "metastasizing
      Spitz's nevus," and "malignant Spitz's nevus" were, in fact, melanomas ( Table
      1). Moreover, in our estimation, those designations, and variants of them, like
      "atypical Spitz's lesion," "atypical dermal melanocytic lesion with features of
      Spitz's nevus," "atypical Spitzoid melanocytic neoplasm," and "problematic
      Spitzoid melanocytic lesion," are mere evasions from a diagnosis,
      straightforwardly, of either Spitz's nevus or melanoma. Diagnoses in pathology
      equally bogus are "minimal deviation melanoma," "borderline melanoma," "nevoid
      melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic lesion
      of uncertain biologic potential." Rather than admit uncertainty forthrightly,
      those who employ circumlocutions like those just mentioned resort to linguistic
      maneuvers that, at first blush, seem to be "academic" and constructed in such a
      way as to appear to convey confidence, rather than tentativeness, on the part of
      a histopathologist. On further scrutiny, however, each of those cliches is
      revealed to be devoid of content. For example, "malignant" Spitz's nevus and
      "metastasizing" Spitz's nevus not only are contradictions in terms, but they are
      outrageous violations of fundamental principles of classic Virchowian pathology,
      and "atypical" Spitz's nevus not only is a redundancy because the neoplasm was so
      atypical to Spitz, herself, she insisted (from the time she spawned the idea in
      194 through 1951 it was a "malignant melanoma," but is abject intellectually,
      those who invoke it never setting forth, in clear-cut fashion, criteria for what
      constitutes a "typical" Spitz's nevus in contradistinction to an "atypical" one.

PMID- 15249863
TI  - The man behind the eponym: Lauren V. Ackerman and verrucous carcinoma of
      Ackerman.
AB  - In 1948, Lauren V. Ackerman described a neoplasm of the oral mucous membrane,
      which he thought represented a unique type of squamous cell carcinoma and that is
      now termed verrucous carcinoma of Ackerman. "Verrucous carcinoma" has also been
      used as a generic term under which are placed giant condyloma of Buschke
      Loewenstein and carcinoma cuniculatum. This report will synopsize the life of
      Lauren Vedder Ackerman, review the original and subsequent report by Ackerman,
      and discuss some other reports of oral verrucous carcinoma. Because this review
      is directed to histopathologists, the histopathology will be emphasized. Other
      aspects of the neoplasm (eg, clinical picture, incidence, etiopathogenesis, and
      treatment) will not be discussed, or if so, only briefly. Giant condyloma
      acuminatum of Buschke-Loewenstein and carcinoma cuniculatum and studies that
      mention the occurrence of Ackerman's verrucous carcinoma in the pharynx, larynx,
      and esophagus will be mentioned only in the section on classification.

PMID- 15249864
TI  - Is melanoma in situ really an in situ neoplasm?

PMID- 15249865
TI  - Persistent nevus, with "no" previous biopsy.

PMID- 15249866
TI  - Monoclonally rearranged gamma T-cell receptor in lichen sclerosus--a finding of
      clinical significance?

PMID- 15249869
TI  - Relationship between cutaneous epithelioid angiomatous nodule and epithelioid
      hemangioma.

PMID- 15249884
TI  - [Digestive system surgery: between the old and the new].

PMID- 15249885
TI  - [Pancreatic transplantation: 1. Indications and results].
AB  - In the face of a rising incidence of diabetes, pancreatic transplantation seems
      to be the only treatment capable of normalizing glycosylated hemoglobin and
      stabilizing or improving the complications of diabetes. To date, more than 19,000
      pancreatic transplantations have been done worldwide. Surgical indications must
      take into account the constraints and risks specific to the diabetic illness, the
      risks of a complex surgical procedure, and the absolute necessity for long term
      immunosuppression. Combined kidney/pancreas transplantation is the most common
      procedure (90% of cases) and is the most effective treatment for renal
      insufficiency due to diabetes. Results have improved significantly over the last
      ten Years due to improvements in the surgical technique and to improvement of
      immunosuppressive regimens. Results are at least as good and perhaps better than
      those achieved in the transplantation of other solid organs; patient survival,
      renal graft survival, and pancreatic graft survival are respectively 95%, 92%,
      and 85% at one Year. Results of pancreatic transplantation alone have improved
      and now seem equal to those of combined organ transplantation. Transplantation
      seems to be cost-effective in the overall care of advanced diabetes, particularly
      in those patients on chronic dialysis or having degenerative complications.

PMID- 15249887
TI  - [Late complication of hiatal hernia surgery].

PMID- 15249886
TI  - [Abdominopelvic actinomycosis: a tumoral syndrome due to bacterial infection].
AB  - The purpose of this review is to define the diagnostic steps and treatment of
      abdominopelvic actinomycosis. Three cases are described which illustrate the
      variety of clinical presentations ranging from acute peritonitis to chronic
      pseudo-tumor. The diagnosis of actinomycosis is rarely made pre-operatively.
      Bacteriologic culture is seldom helpful and imagery findings are non-specific.
      The diagnosis is usually made retrospectively based on histologic examination. In
      women, an intrauterine contraceptive device is often a concomitant factor. Long
      term antibiotic treatment (several Months) with high-dose penicillin-based
      medications is the mainstay of therapy. Despite a high risk of complications,
      surgery is often necessary both for diagnosis and treatment. Resection or
      drainage may diminish the dosage and duration of antibiotic therapy, and helps to
      minimize infectious complications. Actinomycosis should be included in the
      differential diagnosis of abdominopelvic tumors, inflammatory bowel disease, and
      endometriosis-particularly in a woman with an intrauterine contraceptive device.

PMID- 15249888
TI  - [Prosthetic placement to prevent radiation injury of the small intestine].

PMID- 15249889
TI  - [Lysis of the interior of inter-visceral abdominal adhesions].

PMID- 15249890
TI  - [Intraoperative cholangiography during laparoscopic cholecystectomy].

PMID- 15249891
TI  - [Hernia of Morgagni].

PMID- 15249892
TI  - [Preoperative evaluation and management of infectious risk].

PMID- 15249893
TI  - [Which factual arguments regarding the concept of sleep and safety?].

PMID- 15249894
TI  - [18th meeting of the French Society of Digestive Surgery].

PMID- 15249895
TI  - [Imagery of pneumatosis cystica intestinalis].

PMID- 15249896
TI  - [Sigmoid diverticulitis revealing a situs inversus at an advanced age].

PMID- 15249897
TI  - [Childhood asthma].
AB  - The concept of chronicity in asthma, as emphasized by recent definitions of the
      disease, rests on the major characteristics of inflammatory response of the
      airways and progressive development of irreversible structural and functional
      alterations, or so-called airway remodeling. In childhood, however, such
      characteristics as chronicity and irreversibility are debatable. Various clinical
      phenotypes with variable degrees of severity of persistence are found in
      children. Furthermore, many patients with a history of recurrent wheezing in
      early infancy do not develop asthma later in life. The prevalence of asthma,
      especially in its mild forms, has increased markedly in recent years. Although
      the trend has stabilized in Italy, it continues to rise in other Western
      countries. Our research has shown that increased cutaneous response to histamine
      determines a major prevalence of positive skin tests. The rise in clinical forms
      of the disease accompanied by gastrointestinal symptoms is partly attributable to
      the dietary intake of food and beverages processed from environmentally
      engineered products. The features of the new forms of asthma demand accurate
      clinical and functional assessment. In addition to pulmonary function tests,
      determinations for eosinophils and inflammation markers in the blood and sputum,
      noninvasive methods have recently become available to assess airway inflammation.
      Among these, particularly useful studies include test for nitric oxide in exhaled
      air, along with tests for other markers of allergic inflammation and oxidative
      stress in the droplets of the exhaled air. Because in paediatric age, prolonged
      use of inhaled steroids increase the risk of growth impairment, asthma therapy
      should be guided by clinical criteria and examinations, rather than by rigid
      treatment guidelines. Moreover, to secure successful treatment, the parents and
      the child as well should be involved in monitoring the course of the disease.

PMID- 15249898
TI  - [Role of leukotriene antagonists in non-asthmatic disorders].
AB  - It has been shown that the leukotriens play a role in the pathobiologic process
      of allergic asthma and wheezing due to infection. Their specific role in other
      respiratory disorders or in other diseases is not yet fully understood. A recent
      consensus has elaborated the guidelines for the treatment of asthma in the
      paediatric age. According to these guidelines, the leukotriene-antagonists are
      recommended as a possible alternative to inhaled corticosteroids in the long-term
      treatment of mild persistent asthma. The association of antileukotrienes with the
      usual classical therapy led to a great improvement in the treatment of the most
      severe forms of the disease. Moreover, a growing number of disorders such as
      allergic rhinitis, chronic urticaria, atopic dermatitis and nasal polyposis seem
      to benefit from the use of these new drugs. In allergic rhinitis, the most common
      allergic disorder, the leukotrienes seem to be, together with histamine,
      important mediators of both the early and late stage of the allergic reaction.
      They seem to be responsible for the vasodilation and therefore for the nasal
      obstruction. There is a production of leukotrienes also in chronic urticaria,
      which is more frequent in adults, and in atopic dermatitis, which usually has its
      onset in the paediatric age. This paper summarizes the results of several
      clinical trials evaluating the therapeutical efficacy and safety of the
      leukotriene-antagonists. Despite the promising results, further studies are
      however necessary on a greater number of patients before recommending the use of
      this type of drug in this kind of disorders.

PMID- 15249899
TI  - Diagnostic clues in the idiopathic pulmonary fibrosis of children.
AB  - Idiopathic pulmonary fibrosis (IPF) in children is a heterogeneous group of
      progressive disorders characterized by variable extents of inflammation and
      interstitial deposition of collagen fibers with numerous putative triggers.
      Children affected with this condition show breathlessness, non-productive cough
      and bibasilar/inspiratory dry rales. Diagnosis can be obtained by the exclusion
      of all known causes of fibrosing alveolitis such as neoplasms, toxic treatments,
      collagen vascular diseases, occupational exposure or granulomatous diseases.

PMID- 15249900
TI  - Pharmacological strategies in the idiopatic pulmonary fibrosis of children.
AB  - Idiopathic pulmonary fibrosis is characterized by radiographically evident
      interstitial infiltrates and progressive dyspnea with rapid decline of overall
      lung functions. The clinical course of this disease is highly variable; however,
      its prognosis remains poor without adequate and prompt therapeutical support. Due
      to the fact that barely a quarter of patients responds to steroids alone,
      cytostatics are often prescribed simultaneously with low dose corticosteroids in
      the pediatric age too. Cytokine or anti-cytokine therapy and the role of new
      antifibrotic drugs are still at the experimental stage of definition and will be
      discussed in the following review.

PMID- 15249901
TI  - [Endoscopic third ventriculostomy: complications and failures].
AB  - Endoscopic third-ventriculostomy (ETV) became the treatment of choice for non
      communicating hydrocephalus and its effectiveness is largely reported. On the
      contrary, specific articles on complications and failures of this technique are
      very rare and this review aims at supplying further information about it.
      Therefore, an analysis of the main and up-to-date series is made and exhaustive
      data about complications and failures of ETV and about their incidence are
      obtained. The overall frequency rate of complications is 6-20%. Their severity
      may vary either because of the length of the damage (transient or permanent) or
      the value of the involved structures (basilar artery, areas of the CNS,
      hypothalamus) or the importance of the injury (from subclinical sequelae to fatal
      complications). Moreover, this study showed both the risk that the endoscopic
      procedure must be suspended (intra-operative failure) and the risk of an early
      (before 1 month) or delayed (even some years after the intervention) narrowing of
      the ventriculostomy. The rate of and the reasons for failure have been analysed
      and the success of a second ETV has been estimated. The results of this analysis
      suggest that the children proposed for ETV are carefully selected and
      meticulously studied during the follow-up.

PMID- 15249902
TI  - [Intrauterine growth retardation: diagnostic and therapeutic approach].
AB  - Intrauterine growth retardation (IUGR) refers to the fetal growth pattern and
      assumes that at least 2 intrauterine growth assessments are performed, indicating
      a low growth velocity in the fetus. The term "small for gestational age" (SGA)
      does not refer to fetal growth but to the size of the infant at birth. Infants
      with SGA have a low weight and/or length for their gestational age at birth below
      the 10(th) percentile or -2 SD. Approximately 3-5% of all newborns are born SGA.
      The etiology of SGA/IUGR is not known. The majority (80-85%) of infants born SGA
      catch-up within the normal range by 2 years of age. SGA has also been associated
      with increased prevalence of hypertension and dyslipidaemia at a relatively young
      age. Most controlled trials have shown a beneficial effect of GH treatment. The
      growth response seems to be due to the cumulative dose received, parenteral
      adjusted height standard deviation score (SDS) and bone age pretreatment,
      baseline overnight peak of GH and IGF-I levels. During GH treatment, children
      born SGA show a significant increase in fasting levels of insulin and proinsulin
      and a decrease in insulin sensitivity. Fasting glucose levels significantly
      increase. All these effects are reversible upon interruption of treatment.
      However, fasting insulin concentrations as well as glucosylated hemoglobin must
      be carefully monitored during GH treatment. Total cholesterol, LDL cholesterol
      and the atherogenic index significantly decrease during GH treatment. An
      acceleration of bone maturation with GH treatment has been reported even though a
      gain in height SDS for bone age is demonstrated.

PMID- 15249903
TI  - Pulmonary tuberculosis in Italian children by age at presentation.
AB  - AIM: To evaluate the clinical characteristics, diagnostic methods and outcome of
      paediatric pulmonary tuberculosis (PTB) in relation to children's ages when
      observed. METHODS: Children under 15, who had been admitted to the Children's
      Hospital with PTB were prospectively evaluated. Our sample included patients with
      a positive tuberculin skin test and signs or symptoms of tuberculosis (TB),
      including abnormal chest X-rays which suggested PTB. We collected demographic,
      clinical, radiographic and microbiological data from the patients, in addition to
      carrying out contact investigations in order to find a source case. All the
      patients involved in this study were subjected to anti-tuberculosis treatment.
      RESULTS: Sixty-two patients (44% under 5) were eligible for inclusion in our
      study. Children with presenting symptoms were younger than asymptomatic patients
      (p<0.05). A source case was found in 38 patients out of 62 children (62%) and
      children under 5 were more likely to have a source case than that found with
      older children (p<0.05). Ghon complex (infiltrate + adenopathy) tended to occur
      in young children (median age of 3.25, p<0.05). Fourteen children (23%) had
      clinical specimens which tested positive for Mycobacterium tuberculosis (MT), and
      20 (32%) for MT DNA according to a polymerase chain reaction (PCR). Resistant
      strains to 1 or more anti-tuberculosis drugs were found in 5 children and in 4
      adult sources. The patients with minimal or no radiographic change during therapy
      displayed symptoms for a longer period of time and were infected by a resistant
      strain (p<0.05). CONCLUSION: Improvements in case detection, case management and
      contact investigations are necessary for controlling paediatric TB, especially in
      young children. Given that any diagnosis of TB in children is supported by
      epidemiological and clinical evidence rather than isolating MT, detection of the
      source case is important in selecting appropriate treatment.

PMID- 15249904
TI  - Decreasing morbidity of childhood asthma by regular outpatient follow-up, in
      Crete.
AB  - AIM: There is evidence that the prevalence and morbidity of childhood asthma are
      increasing in many countries despite improvement of therapeutic regimens. We
      aimed to study possible changes in childhood asthma morbidity in Crete, Greece,
      by evaluating hospital admissions and emergency room visits for childhood asthma
      before and after 1-year regular follow-up at a special pediatric pulmonary out
      patient clinic. METHODS: We followed-up 118 asthmatic children, aged 1-14 years,
      at a special pediatric pulmonary outpatient clinic. We evaluated the total number
      of hospital admissions due to asthma as well as asthma exacerbations during the
      12 months before and 12 months after the regular follow-up care at the special
      pediatric pulmonary outpatient clinic. RESULTS: The total annual number of
      hospital admissions of the 118 children before and after the regular follow-up
      was 122 and 19, respectively (reduction of 84%). Similarly, the total number of
      asthma exacerbations was 771 before and 230 after the 1-year follow-up (reduction
      of 71%). CONCLUSION: These findings show that regular follow-up care of asthmatic
      children at a specialized pediatric pulmonary outpatient clinic considerably
      reduces the morbidity of childhood asthma, thus reducing hospital costs for
      asthma and improving the quality of life for asthmatic children and their
      families.

PMID- 15249905
TI  - [Vibration risk during neonatal transport].
AB  - AIM: The aim of this paper is to assess the entity of the mechanical vibrations
      which newborn and medical staff are exposed to and to evaluate the possible risks
      connected with excessive exposure. METHODS: Vibrations during a simulated
      emergency ambulance transport were studied. Vibration values with an
      accelerometer at the level of the incubator's mattress and at passengers' and
      pilot's seat level were measured. Mean accelerations (awz) and peak accelerations
      (awpeak), measured using a ponderation filter, according with ISO standard 2631,
      were considered. RESULTS: Inside the incubator an acceleration mean value of 1.33
      (+/-0.13) m/s(2) and peak values of 11.8 (+/-0.1) m/s(2) were found. On
      passengers' seats the awz findings were 0.55 m/s(2) (+/-0.13) and 0.56 m/s(2) (+/
      0.08) while awpeak respectively 4.8 m/s(2) (+/-0.1) and 10.2 m/s(2) (+/-0.1). On
      pilot's seat a mean acceleration of 0.48 m/s(2) (+/-0.08) and an awpeak value of
      4.5 m/s(2) (+/-0.1) were found. CONCLUSION: Peak vibration values which newborns
      are exposed to (11.8 m/s(2)) are high, when compared with acceleration of gravity
      (9.8 m/s(2)); this can provoke repeated jerks. Environmental stress can easily
      alter the stability of an ill newborn and interfere with care manoeuvres.
      Decreasing vibrations in neonatal transport unit could increase the safety of
      newborns, reducing the risks which newborns are actually exposed to.

PMID- 15249906
TI  - [Triage and white codes].
AB  - AIM: In this paper, the authors analyse the type of accesses to the Emergency
      Department of the DEA of the G. Gaslini Institute defined by the triage as White
      Code, monitoring the outcome of said access. METHODS: This investigation was of
      retrospective type and lasted 6 months. It employed the fast track triage nursing
      system for the selection of patients. Independently of their age and sex and
      presenting pathology, the selected patients, at the moment of nursing triage,
      received the white code on the basis of EPM (emergency paediatric medicine)
      paediatric triage guidelines. A specially designed grid containing motivations
      was applied to those admitted to hospital on the basis of the Emergency
      Department judgement. The prospective investigation was facilitated by the
      computerised emergency department patient management system that has been
      operative in our department since June 2000. RESULTS: A total of 22400 white code
      accesses were recruited into the study; the admission percentage was 3.7% (89
      patients). The most frequent reason for hospitalisation was the need to
      clinically classify a pathology that persisted without a complete response.
      CONCLUSION: This preliminary investigation will be pursued in the future with a
      collection of data for organisation type purposes and in order to contribute to
      greater hospital-local district integration.

PMID- 15249907
TI  - Overlap among neurocutaneous syndromes. Observations on encephalocraniocutaneous
      lipomatosis.
AB  - The authors report a case of encephalocraniocutaneous lipomatosis (ECCL) in a
      female infant. Clinical manifestations in this case showed significative overlap
      with another neurocutaneous syndrome, namely oculocerebrocutaneous (OCC)
      Delleman's syndrome. This may support the theory of somatic mosaicism. The
      patient underwent a cerebrospinal fluid (CSF) shunt procedure due to marked
      tetraventricular hydrocephalus that was not present at birth. The need for close
      and multidisciplinary follow-up of these patients is stressed.

PMID- 15249908
TI  - [Cutaneous hyperpigmentation of the distal falanx in a newborn].
AB  - A case of distal falangeal hyperpigmentation in a 2-month female newborn, who did
      not show any other cutaneous disease at the time of our observation, is
      presented. The aim of our study is to focus attention on this condition, actually
      considered a benign, asymptomatic, transitory manifestation, rarely reported in
      literature. On the basis of the clinical features, it has been proposed to add
      this pigmentation to the transient benign dermatoses of newborns.

PMID- 15249909
TI  - [Papular purpuric gloves and socks syndrome. A case report].
AB  - Papulo-purpuric gloves and socks syndrome, a typical maculopurpuric exanthema
      limited to hands and feet, mainly associated with Parvovirus B19 infection, has
      not, until now been reported in the literature in relation to pediatric cases in
      Italy. The case of a 10-year old girl with all the characteristics of the papulo
      purpuric gloves and socks syndrome, as well as being IgM positive anti Parvovirus
      B19, is reported. This syndrome, despite its spontaneous remission, should be
      included in the differential diagnosis of maculopurpuric exanthemas.

PMID- 15249910
TI  - Cyclosporin is safe and effective in severe atopic dermatitis of childhood.
      Report of three cases.
AB  - Severe atopic dermatitis causes major impairment in the life of both children and
      their parents. Generally, symptoms can be controlled with emollients, topical
      steroids, antibiotics, antihistaminic but some patients remain intensely ill and
      may require treatment with systemic steroids and so on. Cyclosporin has been
      found to be effective in a variety of inflammatory skin disorders since it
      reduces the number of activated T-cells expressing interleukin 2 (IL-2)
      receptors. In order to monitor the safety and clinical efficacy of therapy and
      days of remission we performed Cyclosporin on 3 children with severe atopic
      dermatitis, refractory to all traditional therapies. Cyclosporin suspension at
      dosage of 5 mg/kg daily, in 2 doses for 8 weeks has been used. Cyclosporin blood
      levels, liver and kidney function, blood pressure and some immunological
      parameters (eosinophils, IgE, IL-2 receptors) were monitored. All patients showed
      a marked clinical improvement with reduction of pruritus, erythema, papules,
      vesciculation, excoriation, scaly crusts and lichenification. No clinical or
      haematological side effects were demonstrated. The soluble IL-2 receptor
      concentration decreased even after 8 weeks of treatment in all 3 patients,
      regardless of IgE levels (case 1: low IgE level; case 2: very high IgE level) as
      in several others T-cell mediated non IgE-related skin disease. The authors
      suggest that courses of 8 weeks seem effective and safe as well as longer time in
      producing early remission with the advantage of a low cumulative exposure to the
      drug. The main question is whether a prolonged remission will permain as well as
      continuous therapy. This study underscores the potential value of systemic
      administration of this powerful immuno-suppressive agent in the treatment of many
      cases of severe atopic dermatitis working regardless of the IgE values. Although
      3 cases report does not justify any definitive conclusion however it does a
      contribute to understand the heterogeneity of atopic dermatitis and it adds
      information to its current treatment guidelines.

PMID- 15249912
TI  - Three-dimensional echocardiography in children with atrial septal defect.
AB  - The selection of patients for transcatheter or surgical closure of a secundum
      atrial septal defect requires accurate information regarding the anatomy of the
      defect such as its maximal diameter and the amount of circumferential tissue rim.
      Two-dimensional echocardiography is wanting as a means to define selection
      criteria for atrial septal defect closure. Since the defect is visualised from
      multiple orthogonal planes, maximal atrial septal defect diameter is widely under
      estimated. The transcatheter approach measures the stretched diameter, but cannot
      be applied alone for patient selection since it does not provide information on
      the tissue rim. Three-dimensional echocardiography allows unique en face views of
      the atrial septum. Previous studies have shown the ability of 3-dimensional
      echocardiography to depict information regarding the shape, the maximal diameter
      and the rims surrounding the defect. Transthoracic 3-dimensional echocardiography
      is accurate to measure atrial septal defect maximal diameter and rims surrounding
      the defect. Such a non-invasive method could be applied to children selection for
      atrial septal defect closure. The transcatheter balloon method provides
      additional information such as the resistance of the septum. Device sizing and
      placement should take into account both 3-dimensional echocardiography and
      transcatheter findings.

PMID- 15249911
TI  - Overview of interventional pediatric cardiology in 2004.
AB  - Pediatric interventional catheterization is an expanding specialty with a range
      of mature, emerging, and investigative procedures and technologies. Many
      dysfunctional obstructions and/or shunts caused by congenital heart defects may
      be treated or significantly palliated in the catheterization laboratory. These
      include valvar pulmonary or aortic stenosis, the patent ductus arteriosus,
      coarctation of the aorta, branch pulmonary stenosis, atrial septal defects and
      even ventricular septal defects. Valve replacement technology, approaches to
      complex heart diseases such as single ventricle, and fetal interventions are
      subjects of active investigations. A comprehensive review of the present and
      future of interventional pediatric cardiology is presented.

PMID- 15249913
TI  - New developments in the treatment of hypoplastic left heart syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) was once a uniformly fatal disease,
      accounting the majority of neonatal deaths due to congenital heart defects.
      Twenty-five years of advances in the surgical and medical management of this
      disease have resulted in dramatic improvements in survival for these children.
      The goal for patients with HLHS should be survival of near 100% with a good
      quality of life. The advances described in this manuscript detail some of the new
      techniques used in the surgical and medical management. For infants undergoing
      staged reconstruction, the Norwood procedure is performed in the newborn period,
      followed by a hemi-Fontan operation at 6 months of age, and a modified Fontan
      operation at 1 to 2 years of age. A significant recent modification of the
      Norwood procedure is the placement of a right ventricle to pulmonary artery (RV
      PA) conduit instead of a systemic artery to pulmonary shunt (modified Blalock
      Taussig or BT shunt) as the source of pulmonary blood flow. Our recent experience
      with this modification demonstrated an incremental increase in survival, improved
      postoperative stability, and decreased inter-stage mortality. At catheterization,
      significant differences in hemodynamic parameters were present that were
      consistent with improved coronary blood flow, decreased volume load to the single
      right ventricle, and improved pulmonary artery growth in those patients with the
      RV-PA conduit. The 3rd stage in the surgical treatment of HLHS is the modified
      Fontan operation or cavo-pulmonary anastamosis. A new approach for Fontan
      completion is the placement of a stent covered with a thin layer of Goretex from
      the inferior vena cava to the hemi-Fontan baffle. This can be performed in the
      catheterization laboratory, with a decrease in post-procedure pleural effusions,
      lower mortality, and a shorter length of stay. The future of treatment for HLHS
      may eventually involve a single open-heart procedure with initial and final
      interventions being performed in the catheterization laboratory. Some cardiac
      centers perform transplantation for management of HLHS. Survival following
      transplantation has improved as advances in the pre- and post-operative
      management continue, along with new options for immunosuppression. Treatment for
      HLHS continues to evolve, as ongoing work has resulted in improved short and long
      term survival. The future for children with this disease is encouraging as
      evidenced by the remarkable achievements made to date and the current worldwide
      interest and study of HLHS.

PMID- 15249914
TI  - Recent developments and controversies in Kawasaki disease.
AB  - In the developed world, Kawasaki disease is currently the leading cause of
      pediatric acquired heart disease. To date, the etiologic agent remains unknown.
      Many hypotheses regarding the etiology exist, and debate continues as to whether
      the inflammatory response of Kawasaki disease results from a superantigen or a
      conventional antigen. A variety of growth factors, proteinases, and cytokines
      have been identified that are involved in the pathogenesis of coronary artery
      disease in Kawasaki disease. These findings are leading to novel treatment
      strategies in Kawasaki disease, including platelet glycoprotein receptor
      inhibitors and monoclonal antibody to tumor necrosis factor-alpha. The role of
      corticosteroids remains controversial, and ongoing clinical trials are evaluating
      its efficacy. Additional studies have focused on newer non-invasive methods of
      evaluating children with coronary artery disease as alternatives to coronary
      catheterization. We review recent developments and controversies in exploring the
      etiology, pathogenesis, diagnosis, and management of Kawasaki disease.

PMID- 15249915
TI  - The role of radiofrequency ablation for pediatric supraventricular tachycardia.
AB  - Radiofrequency ablation has become frontline therapy for many pediatric patients
      with common supraventricular tachycardia (SVTs). Rather than long-term treatment
      with medications, radiofrequency ablation offers the possibility of "cure" for
      certain SVT substrates. The decision to perform radiofrequency ablation should be
      made after full disclosure with the patient and parents about radiofrequency
      ablation (RFA) benefits and risk, alternative therapies, and the natural history
      of the SVT. This paper presents a discussion about the current status of RFA and
      common pediatric SVTs, as well as, discussing evolving RFA issues and
      indications.

PMID- 15249916
TI  - Infant nutritional recommendations from pediatricians. Epidemiologic survey of
      feeding recommendations for the first year of life in Piedmont.
AB  - AIM: Timing the introduction of solids and milk formulas in infants' diet varies
      throughout the world. The aim of the present study was to assess the modalities
      of weaning, suggested by pediatricians in Piedmont, Italy, and to compare them to
      current scientific guidelines. METHODS: The survey was conducted using data
      recording forms sent to the pediatricians of our area (both practitioners and
      hospital physicians) from September 2000 to January 2001. Pediatricians were
      asked to fill in a questionnaire about the time of solid food introduction in the
      1st year of life. The study was supported by 168 pediatricians, of these 105
      practitioners, 53 hospital doctors and 9 university physicians. RESULTS: The mean
      age of weaning was 4.5 months. The 1st beikost was vegetable soup with rice
      flour, meat and parmesan in 65.4%; in 73.8% it was given with a spoon. In 94.6%
      no salt was added, in 84.5% no sweetener was added. Homogenized fruit was
      introduced at a mean age of 4.4 months: apple was the 1st fruit to be introduced
      (4.5 months), followed by pear (4.8 months) and banana (5.6). Lyophilised meat
      was introduced at 5 months, homogenized meat was introduced at 6.2 months, and
      minced meat was introduced at 8.2 months. Vegetables (potatoes, carrots,
      courgettes) were introduced between 5.2 to 5.4 months of age. Parmesan was
      introduced at 5.3 months; gluten at 6.2 months. Egg yolk was the 1st to be
      introduced (mean age = 8.9 months), while albumen was introduced at a mean age of
      11.6 months. Fish was given at a mean age of 8.2 months. Cow's milk was
      introduced at 9 months. CONCLUSION: Paediatricians give indications about the
      introduction of solid foods according to scientific guidelines, with the
      exception of cow's milk which is introduced too early.

PMID- 15249917
TI  - [Risk assessment for eating disorders in a high school: a study based on the
      Eating Attitudes Test 26].
AB  - AIM: Disordered eating behaviours can lead to clinically evident and serious
      eating disorders (ED). Aim of this paper is to determine their extent among
      adolescents and to evaluate the associated characteristics. METHODS: All students
      of a high school (age 14-18) have been asked to fill up the Eating Attitudes Test
      (EAT-26) anonymously. EAT-26 is a self-reported questionnaire identifying
      subjects at risk for ED. This questionnaire included also an integrative section,
      aimed at investigating some ED-related variables (family composition, diet among
      relatives, social relationships, spare time activities, self-esteem). Collected
      data have been analyzed using EpiInfo6. RESULTS: The study involved all the 902
      students of the school; 833 questionnaires have been distributed and 701 were
      collected (89.4% from girls, 10.3% from boys). The percentage of EAT-26 positive
      boys (i.e. scoring = or > 20) is 3%, while for girls is 13.7%. A positive test
      significantly correlates with low self-esteem (OR = 46.67, CI = 13.16-182.04),
      contentious relationships with the mother (OR = 2.20, CI = 1.12-4.29) and the
      father (OR=2.45, CI=1.24-4.80). No significant correlation has been found for
      being an only child, living in a single-parent family having limited/not having
      social relationships, having unsatisfactory social relationships, spending spare
      time mostly alone, watching TV more than 2 h per day. CONCLUSION: Our data
      suggest an increasing diffusion in the risk for ED among adolescents. Personal
      characteristics and behaviours related to this risk are good start points to
      program projects focusing on primary and secondary prevention of ED in high
      schools.

PMID- 15249918
TI  - [Primary ad secondary gastro-esophageal reflux in pediatric age].
AB  - AIM: This study takes into consideration children traited for: a) "primary"
      gastro-esophageal reflux (GER); b) GER "secondary" to delayed gastric emptying;
      c) some congenital anomalies which can cause or favour GER in pediatric age.
      METHODS: During 2002, 21 infants or children operated on for "primary" or
      "secondary" GER and 62 patients operated on for esophageal atresia, diaphragmatic
      hernia or abdominal wall defect were followed-up to evaluate the frequency and
      the course of post-operative GER. RESULTS: Patients with "primary" GER had 14%
      relapses after partial or total fundoplication; all patients with "secondary" GER
      submitted to fundoplication, usually associated to pyloroplasty, had 0% relapses.
      One child, after Bianchi's operation, developed an erosive gastritis. Variable
      degrees of GER developed in 43% of patients operated on for esophageal atresia,
      in 25% for congenital diaphragmatic hernia and in 0% for abdominal wall defect.
      In 90% of GER occurred after treatment of esophageal atresia and in 100% of
      diaphragmatic hernia (predominantely "acquired") an exclusively medical therapy
      was successfully performed. CONCLUSION: The conclusion is drawn that: a) the
      relatively high percentage of relapses after fundoplication in "primary" GER may
      be related to an incorrect classification of a few number of cases ("secondary"
      GER considered--and treated--like "primary" GER in the '70s and '80s years?); b)
      fundoplication associated to a best gastric-emptying operation (pyloroplasty) may
      lead to excellent results in secondary GER; c) esophageal atresia and congenital
      diaphragmatic hernia (not including the abdominal wall defects) can cause GER in
      most cases responsive to simple medical therapy.

PMID- 15249919
TI  - [Neuropsychological profiles in preterm low birth weight children].
AB  - AIM: Several studies focus on the psychic development of extremely low birth
      weight (ELBW) preterm infants and highlight the presence of neurological,
      cognitive and relating disorders. Several contributions have in fact shown that
      in these subjects in school age disturbances of cognitive functions may be
      encountered; in particular, disturbances of specific neuropsychological
      functions, such as attention defects, impaired visuo-spatial function, memory and
      language have been reported in subjects with a globally normal intelligence
      quotient. METHODS: Forty-three school-aged children were studied (21 males and 22
      females). They had a low birth weight (weight between 1,050-2,450 g), the
      gestation period was between 29 and 32 weeks and they were compared with a
      control sample whose birth weight was >2,500 g. Cognitive development was
      assessed by a test battery including WISC-R, Zazzo "deux Barrage" Test, Benton
      Visual Retention Test and Frostig Developmental Test of Visual Perception.
      Parents were also called in to evaluate how they had experienced the birth of
      their child and how long the mother had been kept in the clinic. RESULTS: The
      overall analysis of our study suggests normal cognitive development in these
      children. No significant diffences were detected in the 2 studied groups. The
      lack of differences could be associated with the criteria used to select our
      sample because no children with severe perinatal disorders were included in the
      study. In addition, a good mother-child relationship seems to have been
      established in these children and this has certainly contributed to cognitive
      development adequate to their age. CONCLUSION: The prognosis of these children is
      therefore closely related both to the birth weight and, especially, to the
      difficulties faced in the neonatal age (severe perinatal diseases).

PMID- 15249920
TI  - [Sport activity in children and adolescents: temperament and emotional traits].
AB  - AIM: Aim of this study is to evaluate anxiety and temperament characteristics in
      developmental age subjects who practised agonistic sport (individual or team
      sports) in comparison with a sample group of subjects who practice no agonistic
      sports. METHODS: Sixty subjects aged from 10 to 16 years were enrolled in the
      study and divided into 3 groups: 20 subjects practised individual agonistic sport
      (Group A), 20 subjects practised team agonistic sports (Group B) and 20 subjects
      who practised non agonistic sport as control group, (Group C). The following
      tests were used: multidimensional anxiety scale for children (MASC) to evaluate
      anxiety, EAS scale (Buss e Plomin) to evaluate temperament (emotionability,
      activity, sociability and shyness for younger children). RESULTS: MASC scale
      scores underline generalized anxiety with higher significantly score in subjects
      who practised agonistic sports (Group A and B) compared with Group C. Anxiety
      symptoms were more evident in subjects who practised individual discipline
      compared with those who practised team sports. EAS scale indicated that
      temperament of subjects who practised agonistic sport was characterised by a
      considerable aptitude for sociability with low emotionability/activity levels in
      comparison to control group. CONCLUSION: None of the 3 groups showed a
      psychopathologic profile.

PMID- 15249921
TI  - Autosomal malignant osteopetrosis. From diagnosis to therapy.
AB  - Osteopetrosis is a heterogeneous family of rare human genetic disorders due to
      markedly decreased bone resorption. It is one among disorders causing
      osteosclerosis of the trabecular bone and/or hyperostosis of the cortical bone.
      Four types of human osteopetrosis have been clearly defined, but patients with
      atypical symptoms are frequent, suggesting that there are additional forms. The
      most severe expression of this condition in its malignant form is inherited as an
      autosomal recessive disorder and it is usually fatal before school age. It
      presents with failure to thrive, severe hepatosplenomegaly, pancytopenia and
      nerve compression leading to blindness and deafness during infancy. The case of a
      2-month-old female child with severe hepatosplenomegaly, failure to thrive,
      nystagmus, pancytopenia, gengival hyperplasia, optic atrophy, absent evoked
      visual potential and increased bone density within the total skeleton, is
      reported. Diagnosis of autosomal recessive malignant osteopetrosis was
      established by transiliac bone biopsy. She underwent bone marrow transplantation,
      but died soon afterwards. This rare and mortal disorder of bone formation
      requires early diagnosis and immediate pharmacological treatment, consisting in
      administration of vitamin D, in order to enhance bone resorption and of
      prednisone to improve hematological indexes and, if possible, bone marrow
      transplantation in order to ameliorate quality of life and survival.

PMID- 15249922
TI  - [Scrofuloderma. a clinical case].
AB  - Scrofuloderma is a form of colliquative cutaneous tuberculosis resulting from the
      spread of an underlying focus, generally represented by lymphnodes;
      osteoarticular tubercular locations or epididimus locations can also lead to
      ulcerative cutaneous involvement. We report the case of a female patient aged 12
      who had been in Italy for 15 days following her arrival from Marocco. In the left
      clavicular region she presented an ulcerated lesion with palpable lymphnodes on
      the corresponding side of the neck. Histopathological examination of one of the
      involved lymphnodes suggested a mycobacteriosis; differential diagnosis was
      carried out between MAIS (M. avium, M. intracellulare, M. scrofulaceum) group
      mycobacteria infection and tuberculosis. Bacteriological research in the
      lymphnode of alcohol-acid resistant bacilli gave a negative result, while
      cultural examination and protein chain reaction pointed to M. tuberculosis. The
      patient was subjected to combined treatment based on rifampycin, isoniazide,
      etambutolol and pyrazinamide. At the present time, tuberculosis is an important
      public health problem in developing countries. In western countries such as the
      United Kingdom, which have been open to immigration for a longer time,
      scrofuloderma is present with higher prevalence in immigrants from Asia and
      Africa; in these immigrant populations, this tubercular form involves a wide age
      segment between the ages of 10 and 50. In the autochthonous population the
      highest incidence is in subjects aged more than 50. In Italy too, extra
      communitary immigration has also contributed, with a delay compared to other
      western countries, to bring tuberculosis back into the public eye after a period
      of decades during which it was wrongly considered to have disappeared.

PMID- 15249923
TI  - [Prevalence of breast feeding at the ASL 11--Piedmont Region].

PMID- 15249924
TI  - Hyperparathyroidism.
AB  - Hyperparathyroidism is a disease characterized by hypercalcemia with
      hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH).
      The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary
      (secondary refractory form). Primary hyperparathyroidism is rare in children;
      hyperplasia is more frequent during the early years of life (neonates and
      infants) and is difficult to distinguish from adenoma in children. The disease
      may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied
      by anorexia, asthenia and persistent stipsis; severely elevated concentrations
      (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with
      dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or
      osteitis fibrosa cystica may be present due to augmented bone resorption. Height
      and weight increases are altered due to anorexia and dehydration. Differential
      diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D
      intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia.
      Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca
      >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system,
      the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment
      are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of
      the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found
      in cases where chronic hypocalcemia is present, particularly in chronic renal
      failure, untreated deficiency rickets, chronic intestinal malabsorption,
      hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular
      acidosis or Fanconi's syndrome. The tertiary form is distinguished by the
      autonomous nature of the parathyroid glands which have become
      hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It
      can also be of iatrogenic origin due to excessive intake of inorganic phosphates
      in familial hypophosphatemic rickets or chronic vitamin D deficiency.

PMID- 15249925
TI  - Pharmacogenetic approaches to rheumatoid arthritis.

PMID- 15249926
TI  - Spinal cord infarction secondary to intervertebral foraminal disease.
AB  - STUDY DESIGN: The 5 year review of patients referred to one center. OBJECTIVE: To
      report spinal cord infarction secondary to vascular occlusion from disease in a
      lower thoracic intervertebral foramen. METHOD: The clinical and imaging findings
      of two cases with acute spinal cord dysfunction are presented. SETTING: Midlands
      Centre for Spinal Injuries, England. RESULTS: The CT and MR imaging features
      revealed lower thoracic unilateral foraminal occlusion due to acute facet joint
      septic arthritis in a diabetic patient, and secondary to chronic hypertrophic
      osteophytes in a second hypertensive individual. The presumed mechanism of
      infarction was occlusion of the artery of Adamkiewicz. CONCLUSION: Foraminal
      disease in the lower thoracic levels needs to be entertained in cases of
      unexplained nontraumatic acute spinal cord dysfunction.

PMID- 15249927
TI  - An unusual use of AMS 800 artificial urinary sphincter cuff in the treatment of
      sphincteric neurogenic incontinence: case report.
AB  - STUDY DESIGN: Case report of an unusual use of AMS 800 (American Medical Systems,
      Inc., Minnetonka, Minnesota) artificial urinary sphincter cuff in a female
      patient affected by neurogenic urinary incontinence. OBJECTIVE: To describe this
      rare surgical solution. SETTING: Department of Urology in Italy. METHODS: A 43
      year-old woman affected by flaccid paraplegia, acontractile bladder and
      incompetent bladder neck, underwent an implantation of an artificial urinary
      sphincter AMS 800. After 7 years, a mechanical failure of the device occurred and
      pubovaginal sling (PVS) utilizing the cuff of the sphincter was employed due to
      the poor quality of rectus fascia and the development of previous allergy for
      some heterologous materials. RESULTS: At 17 months follow-up, the patient is
      content and able to empty the bladder by clean intermittent self-catheterization
      (CIC). CONCLUSION: The risk of developing an allergy reaction due to the
      employment of heterologous materials and the impossibility to use the rectus
      fascia obliged us to adopt the pre-existent cuff of the artificial urinary
      sphincter AMS 800.

PMID- 15249928
TI  - Utilization of health services following spinal cord injury: a 6-year follow-up
      study.
AB  - STUDY DESIGN: Cohort study with 6-years follow-up. OBJECTIVE: To describe the
      utilization of health services by persons with spinal cord injury (SCI) and
      compare it with that of the general population. SETTING: Alberta, Canada.
      METHODS: All persons who sustained an SCI in Alberta between April 1992 and March
      1994 were followed from date of injury to 6 years postinjury. Cases were matched
      (1:5) with controls randomly selected from the general population and matched for
      age, gender, and region of residence. Administrative data from centralized health
      care databases were compiled to provide a complete picture of health care use,
      including hospitalizations, physician contacts, long-term care admissions, home
      care services, and the occurrence of secondary complications. RESULTS: In all,
      233 individuals with SCI and 1165 matched controls were followed for 6 years.
      Compared with the control group, persons with SCI were rehospitalized 2.6 times
      more often, spent 3.3 more days in hospital, were 2.7 times more likely to have a
      physician contact, and required 30 times more hours of home care services. Of
      those with SCI, 47.6% were treated for a urinary tract infection, 33.8% for
      pneumonia, 27.5% for depression, and 19.7% for decubitus ulcer. CONCLUSION: SCI
      places a heavy burden on the health care system. Persons with SCI have greater
      rates of contact with the health system compared with the general population.
      Secondary complications continue to affect persons with SCI long after the acute
      trauma.

PMID- 15249929
TI  - Preservation of fecal continence and bowel function after radical perineal and
      retropubic prostatectomy: a questionnaire-based outcomes study.
AB  - PURPOSE: To assess fecal incontinence rates and bowel function for radical
      perineal (RPP) or radical retropubic (RRP) prostatectomy patients and to compare
      them with a matched control group. METHODS: The bowel function domain of the
      Expanded Prostate Cancer Index Composite (EPIC) was mailed to 150 consecutive
      patients who had undergone RPP (79) or RRP (71) by the same surgeon (HJK) and an
      age-matched control group (75). RESULTS: Fecal incontinence and bowel dysfunction
      were statistically equivalent for the study groups. CONCLUSIONS: There is no
      difference in fecal incontinence rates or bowel function when comparing RPP
      patients to RRP or control patients.

PMID- 15249930
TI  - Adding space and colour, without tying yourself in a knot, at the bladder neck
      urethral stump anastomosis during radical prostatectomy.

PMID- 15249931
TI  - Proerectile pharmacological prophylaxis following nerve-sparing radical
      prostatectomy (NSRP).
AB  - The importance of an early pharmacological prophylaxis for erectile function
      following nerve-sparing radical prostatectomy has been recently stressed by
      several authors. In spite of that, patient's compliance to erectile
      rehabilitation protocols seems to be low. The present review is an attempt to
      define the expected benefits of the currently proposed rehabilitative protocols
      in terms of cost-efficiency and quality of life. The conclusion is that current
      scientific evidence in support of an early postoperative use of erectile aids is
      based mainly on indirect proof of a cavernosal damage that may follow the
      temporary postoperative 'erectile silence'. Intracavernosal injections or a
      vacuum device may represent the best first-line treatment option for the first
      few months from the procedure as their mechanism of action does not require
      intact neural tissue for erection. Thereafter oral phosphodiesterase 5 inhibitor
      therapy may be a reasonable choice for those patients who can achieve at least a
      partial erection. A phosphodiesterase 5 inhibitor may not be effective when
      spontaneous erections are absent. It is possible, since the rehabilitation of
      sexual function aims to prevent cavernosal tissue damage by providing oxygenation
      to the erectile tissue, the choice of a potentially ineffective treatment may
      jeopardize the results of a reasonable nerve-sparing procedure.

PMID- 15249932
TI  - Support for EKN1 as the susceptibility locus for dyslexia on 15q21.
AB  - Dyslexia has been linked to a number of chromosomal regions including 15q.
      Recently a gene, EKN1, with unknown function in the linked region, was identified
      via a translocation breakpoint. This gene was further supported as a
      susceptibility locus by association studies in a Finnish sample. We investigated
      the possibility of this locus as a susceptibility gene contributing to dyslexia,
      analyzed as a categorical trait, and analyzed key reading phenotypes as
      quantitative traits using six polymorphisms including the two previously reported
      to be associated with dyslexia. In our sample of 148 families identified through
      a proband with reading difficulties, we found significant evidence for an
      association to dyslexia analyzed as a categorical trait and found evidence of
      association to the reading and related processes of phonological awareness, word
      identification, decoding, rapid automatized naming, language ability, and verbal
      short-term memory. However, association was observed with different alleles and
      haplotypes than those reported to be associated in a Finnish sample. These
      findings provide support for EKN1 as a risk locus for dyslexia and as
      contributing to reading component processes and reading-related abilities. Based
      on these findings, further studies of this gene in independent samples are now
      required to determine the relationship of this gene to dyslexia.

PMID- 15249933
TI  - A genome scan and follow-up study identify a bipolar disorder susceptibility
      locus on chromosome 1q42.
AB  - In this study, we report a genome scan for psychiatric disease susceptibility
      loci in 13 Scottish families. We follow up one of the linkage peaks on chromosome
      1q in a substantially larger sample of 22 families affected by schizophrenia
      (SCZ) or bipolar affective disorder (BPAD). To minimise the effect of genetic
      heterogeneity, we collected mainly large extended families (average family size
      >18). The families collected were Scottish, carried no chromosomal abnormalities
      and were unrelated to the large family previously reported as segregating a
      balanced (1:11) translocation with major psychiatric disease. In the genome scan,
      we found linkage peaks with logarithm of odds (LOD) scores >1.5 on chromosomes 1q
      (BPAD), 3p (SCZ), 8p (SCZ), 8q (BPAD), 9q (BPAD) and 19q (SCZ). In the follow-up
      sample, we obtained most evidence for linkage to 1q42 in bipolar families, with a
      maximum (parametric) LOD of 2.63 at D1S103. Multipoint variance components
      linkage gave a maximum LOD of 2.77 (overall maximum LOD 2.47 after correction for
      multiple tests), 12 cM from the previously identified SCZ susceptibility locus
      DISC1. Interestingly, there was negligible evidence for linkage to 1q42 in the
      SCZ families. These results, together with results from a number of other recent
      studies, stress the importance of the 1q42 region in susceptibility to both BPAD
      and SCZ.

PMID- 15249934
TI  - A one-pot synthesis to [(Me3Si)3SiSb]4; a potential precursor for Sb42-.
AB  - The reaction of (Me(3)Si)(3)SiK[middle dot]18-crown-6 with SbCl(3)(3 : 1 equiv.)
      provides a simple route to the title complex [(Me(3)Si)(3)SiSb](4). The potassium
      base initially acts as a nucleophile and then as a coupling agent, forming Sb-Sb
      bonds.

PMID- 15249935
TI  - A neutral tungsten-eta2-alkyne-1-thio ligand forming a homoleptic Werner type
      complex with Cu(I).
AB  - The 1-thio-eta2-alkyne-complex [Tp'(CO)2W(BnSCCS)][Tp'= hydrotris(3,5
      dimethylpyrazolyl)borate; Bn = benzyl], which was obtained by reductive removal
      of the benzyl group at the alkyne complex [Tp'(CO)2W(BnSCCSBn)]PF(6), has been
      established as a ligand in a combined organometallic/Werner type heterobimetallic
      complex with Cu(I).

PMID- 15249936
TI  - Synthesis and structural characterisation of a cationic trinuclear organobismuth
      complex with an unprecedented coordination mode of hydrotris(2
      mercaptoimidazolyl)borate ligands.
AB  - A new coordination mode of hydrotris(2-mercaptoimidazolyl)borate ligands was
      found in the reaction of [Na(Tm(tBu))] with Me(2)BiCl to form a trinuclear
      organobismuth complex [(Me(2)Bi)(3)(Tm(tBu))(2)](+)[Me(2)BiCl(2)](-)(Tm(tBu)=
      hydrotris(2-mercapto-1-tert-butylimidazolyl)borate).

PMID- 15249937
TI  - Transition metal-catalyzed ring-opening polymerization (ROP) of strained, silicon
      bridged bis(benzene)chromium complexes.
AB  - Silicon-bridged bis(benzene)chromium complexes (sila[1]chromarenophanes) undergo
      facile transition metal-catalyzed ROP at ambient temperature in the presence of
      Karstedt's catalyst to yield polychromarenylsilanes, the first homopolymers with
      main chains of Cr(arene)(2) and organosilane units.

PMID- 15249938
TI  - Mild mono and double demethylation in dimethylsulfonium substituted
      ruthenacarborane complexes. A regioselective reaction.
AB  - Reaction of [RuCl(2)(eta(6)-C(6)H(6))](2) with [10-(CH(3))(2)S-7,8-nido
      C(2)B(9)H(10)](-) or [9-(CH(3))(2)S-7,8-nido-C(2)B(9)H(10)](-) afforded the
      expected cationic complexes [Ru(eta(5)-n-(CH(3))(2)S-7,8-C(2)B(9)H(10))(eta(6)
      C(6)H(6))](+)(n= 10, (1); 9, (3)), but also the unexpected neutral Ru(eta(5)-10
      HS-7,8-C(2)B(9)H(10))(eta(6)-C(6)H(6))(2) or Ru(eta(5)-9-(CH(3))S-7,8
      C(2)B(9)H(10))(eta(6)-C(6)H(6))(4) by double and mono demethylation of the
      (CH(3))(2)S moiety, respectively.

PMID- 15249939
TI  - The design of a continuous reactor for fluorous biphasic reactions under pressure
      and its use in alkene hydroformylation.
AB  - A reactor, into which all reagents can be fed continuously and from which the
      reaction mixture can be continuously removed to a gravity separator, where
      product can be continuously removed and the catalyst phase recycled to the
      reactor, has been constructed and used for the hydroformylation of alkenes in
      fluorocarbon solvents.

PMID- 15249940
TI  - Crystal engineering of a versatile building block toward the design of novel
      inorganic-organic coordination architectures.
AB  - Six novel inorganic-organic coordination supramolecular networks based on a
      versatile linking unit 4-pyridylthioacetate (pyta) and inorganic Co(II), Cu(II),
      Ag(I), Zn(II), Mn(II) and Pb(II) salts have been prepared in water medium and
      structurally characterized by single-crystal X-ray diffraction analysis. Reaction
      of CoCl(2).6H(2)O with Hpyta afforded a neutral mononuclear complex
      [Co(pyta)(2)(H(2)O)(4)](1), which exhibits a two-dimensional (2-D) layered
      architecture through intermolecular O-HO interactions. Reaction of CuCl(2.2H(2)O
      with Hpyta yielded a neutral one-dimensional (1-D) coordination polymer
      [[Cu(pyta)(2)(H(2)O].0.5H(2)O](n)(2) consisting of rectangle molecular square
      units, which show a three-dimensional (3-D) supramolecular network through S...S
      and O-H...O weak interactions. However, when AgNO(3), Zn(OAc)(2).2H(2)O or
      MnCl(2).4H(2)O salts were used in the above self-assembled processes, the neutral
      2-D coordination polymers [Ag(pyta)](n)(3), [[Zn(pyta)(2)].4H(2)O](n)(4) or
      [[Mn(pyta)(2)(H(2)O)]](n)(5) with different topologies were obtained,
      respectively. While substituting the transition metal ions used in 1-5 with
      Pb(OAc)(2).3H(2)O, a one-dimensional coordination polymer [Pb(pyta)(2)](n)(6),
      which shows a novel 2-fold interpenetrating 2-D supramolecular architecture
      through weak SS interactions, was isolated. It is interesting to note that the
      building block pyta anion exhibits different configurations and coordination
      modes in the solid structures of complexes 1-6. These results indicate that the
      versatile nature of this flexible ligand, together with the coordination
      preferences of the metal centers, play a critical role in construction of these
      novel coordination polymers or supramolecules. The spectral and thermal
      properties of these new materials have also been investigated.

PMID- 15249941
TI  - Blue phosphorescent Zn(II) and orange phosphorescent Pt(II) complexes of 4,4'
      diphenyl-6,6'-dimethyl-2,2'-bipyrimidine.
AB  - To investigate the different phosphorescent promoting effects of organic emitters
      by various metal centers, a new ligand, 4,4'-diphenyl-6,6'-dimethyl-2,2'
      bipyrimidine (pmbp), and its Zn(II), Hg(II), and Pt(II) complexes,
      [Zn(pmbp)(2)](ClO(4))(2)(1), Pt(pmbp)Ph(2)(2), Zn(pmbp)Cl(2)(3), and
      Hg(pmbp)Cl(2)(4) were synthesized. Their structures were determined by single
      crystal X-ray diffraction. The zinc complexes 1 and 3 exhibit blue luminescence
      in the solid state at ambient temperature, but the mercury complex 4 is not
      luminescent. At 77 K, both pmbp and complex have blue emissions in MeOH
      solutions, which were demonstrated to be phosphorescence by their long decay
      lifetime (micros). By comparing the luminescent properties of the free ligand and
      the complex, we concluded that the phosphorescence of originates from ligand
      centered pi --> pi* transitions. Complex 2 exhibits orange luminescence both in
      CH(2)Cl(2) solution at 77 K and in the solid state at ambient temperature, which
      was assigned to metal-to-ligand [d(M) --> pi*(pmbp)] charge transfer (MLCT). The
      different origin of luminescence is responsible for the different luminescent
      color of the Zn(II) and Pt(II) complexes.

PMID- 15249943
TI  - A series of novel lanthanide polyoxometalates: condensation of building blocks
      dependent on the nature of rare earth cations.
AB  - A series of novel lanthanide polyoxomolybdates was synthesized by reaction of
      lanthanide cations with the Anderson type anion (TeMo(6)O(24))(6-). The
      polyoxometalates
      K(6n)(TeMo(6)O(24))(n)[(Ln(H(2)O)(7))(2)(TeMo(6)O(24))](n)[middle dot]16nH(2)O
      (Ln = Eu, Gd) and K(3n)[Ln(H(2)O)(5)(TeMo(6)O(24))](n)[middle dot]6nH(2)O (Ln =
      Tb, Dy, Ho, Er) were characterized by X-ray structure analysis, elemental
      analysis and IR spectroscopy. We found that the solid-state structures of
      Ln/(TeMo(6)O(24))(6-) compounds are strongly dependent on the lanthanide cations,
      and therefore represent a rare example for different arrangements of building
      units depending on the nature of the rare earth cations. While the Eu(3+) and
      Gd(3+) cations achieve ninefold coordination by seven water molecules and two
      terminal oxygen atoms of the (TeMo(6)O(24))(6-) anions, the Tb(3+), Dy(3+),
      Ho(3+) and Er(3+) cations are coordinated by five water molecules, two terminal
      oxygen atoms and one molybdenum-bridging oxygen atom belonging to the
      (TeMo(6)O(24))(6-) anion. The europium and gadolinium substituted compounds
      contain infinite one-dimensional [(Ln(H(2)O)(7))(2)(TeMo(6)O(24))](n) chains; the
      terbium, dysprosium, holmium and erbium compounds contain infinite one
      dimensional [Ln(H(2)O)(5)(TeMo(6)O(24))](n)(3n-) chains.

PMID- 15249942
TI  - Structure and bonding in the isoelectronic series CnHnP5-n+: is phosphorus a
      carbon copy?
AB  - The relative stabilities of different isomers of the isoelectronic series
      C(n)H(n)P(5-n)(+) have been investigated using G3X theory. The results indicate
      that all species containing one or more phosphorus atom adopt a three-dimensional
      nido geometry, in marked contrast to the planar structure favoured by the all
      carbon analogue. Within isomeric nido clusters, a strong correlation between
      total energy and the nucleus-independent chemical shift (NICS) indicates that
      three-dimensional aromaticity plays a significant role in determining the
      stability of the cluster. In the context of these nido clusters, the extent to
      which phosphorus is a carbon copy proves to be highly dependent on the global
      electronic environment. The first isolobal substitution of CH by P causes a
      complete switch from localised to delocalised bonding, accompanied by a
      transition from a two- to a three-dimensional structure, with the phosphorus atom
      showing a strong preference for the unique apical site. In contrast, further
      increasing the phosphorus content causes no further change in structure or
      bonding, suggesting that, at the basal sites, phosphorus is a rather better
      carbon copy. The low-energy pathways for interconversion of apical and basal
      atoms previously identified in C(2)H(2)P(3)(+) prove to be a general feature of
      all members of the series.

PMID- 15249945
TI  - Interactions of Cu2+ ions with chicken prion tandem repeats.
AB  - The potentiometric and spectroscopic (EPR, UV-Vis, CD) data have shown that the
      chicken prion hexa-repeat (Ac-His-Asn-Pro-Gly-Tyr-Pro-NH(2)) is a very specific
      ligand for Cu(2+) ions. The His imidazole is an anchoring binding site, then the
      adjacent amide nitrogen coordinates as a second donor. The presence of Pro at
      position 3 induces binding of phenolate oxygen as a third donor atom. The
      tridentate coordination dominates around physiological pH. Similar to human
      octapeptide fragments, chicken tandem repeats exhibit a cooperative effect in
      binding Cu(2+) ions, although chicken peptides are much less effective in metal
      ion coordination.

PMID- 15249946
TI  - New insights into catalytic hydrogenation by phosphido-substituted triruthenium
      clusters: confirmation of intact cluster catalysis by parahydrogen NMR.
AB  - The phosphido-substituted triruthenium cluster Ru(3)(CO)(9)(mu-H)(micro-PPh(2))
      is shown to react with H(2) to form the trihydride cluster Ru(3)(CO)(9)(H)(mu
      H)(2)(mu-PPh(2)), which undergoes a number of re-arrangement reactions on heating
      to yield other phosphido-substituted triruthenium clusters. In the presence of
      alkyne substrates, heating the system leads to catalytic hydrogenation via CO
      loss and the formation of a Ru(3)(eta(2)-PhC[double bond, length as m
      dash]CHPh)(CO)(8)(micro-H)(PHPh(2)) resting state, in a reaction affected by the
      polarity of the solvent. No mononuclear fragments are observed in the catalytic
      transformation, confirming directly that the phosphido ligand is able to exert a
      stabilising influence on the cluster core.

PMID- 15249944
TI  - Aerial oxidation of primary alcohols and amines catalyzed by Cu(II) complexes of
      2,2'-selenobis(4,6-di-tert-butylphenol) providing [O,Se,O]-donor atoms.
AB  - Seven copper(II)-complexes 1-7 with the ligand 2,2'-selenobis(4,6-di-tert
      butylphenol) providing [O,Se,O]-donor atoms have been isolated and characterized.
      Three of them 1, 2 and 3 are mononuclear, two 4 and 7 dinuclear and 5, 6 are
      trinuclear. The crystal structures of the complexes were determined by X-ray
      diffraction and the electronic structures were established by various physical
      methods including EPR and variable temperature (2-290 K) susceptibility
      measurements. The magnetic behaviour of the compounds 4-6 exhibits
      antiferromagnetic exchange coupling resulting in well-isolated S(t)= 1/2 ground
      state for 5 and 6 and a diamagnetic spin state for 4. Complexes 5 and 6 belong to
      the class of asymmetric trinuclear copper(II) complexes modelling the trinuclear
      copper site in multicopper oxidases. Complex 1 is a catalyst in the presence of a
      strong base for the aerial oxidation of primary alcohols to the corresponding
      aldehydes. A dinuclear complex, seemed to be 4, prepared in situ has been found
      to be a catalyst for the aerial oxidation of primary amines containing alpha-C-H
      atoms. Primary kinetic isotope effects show that H-abstraction from the alpha
      carbon atom of a coordinated substrate (alcoholato or amine) is the rate
      determining step in both cases. Two functional models for the metalloenzymes
      galactose oxidase and amine oxidases are thus described.

PMID- 15249947
TI  - Tren centered tris-macrocycles as polytopic ligands for Cu(II) and Ni(II).
AB  - Two novel symmetric polytopic ligands L(1) and L(2) have been synthesized. They
      are composed of three 1,4,8,11-tetraazacyclotetradecane macrocycles which are
      connected to a central tren moiety via an ethylene and a trimethylene bridge,
      respectively. The complexation potential and the speciation diagrams of L(1) and
      L(2) towards Cu(2+) and Ni(2+) were determined by spectrophotometric and
      potentiometric titrations. Insight into the geometry of the Cu(2+) complexes is
      provided by UV-VIS and EPR spectroscopy. The simplified ligands L(3) and L(4) are
      utilized as references for an aminoethyl- and a tren-substituted tetraaza
      macrocycle to help assign the EPR spectra of the polytopic ligands L(1) and L(2).
      At a metal-to-ligand ratio of 3 : 1, the metal cations are preferentially bound
      to the tetraaza macrocycles of L(1) and L(2) in a square planar geometry. At high
      pH values, a nitrogen atom of the tren moiety in L(1) serves as an additional
      ligand in an axial position leading to a square pyramidal coordination around
      Cu(2+), whereas in L(2) no such geometry change is observed. At a metal-to-ligand
      ratio of 4 : 1, the additional metal cation resides in the central tren moiety of
      L(1) and L(2). However, in contrast to the typical trigonal bipyramidal geometry
      found in the [Cutren](2+) complex, the fourth Cu(2+) has a square pyramidal
      coordination caused by the interaction with the Cu(2+) cations in the macrocycles
      (as evidenced by EPR spectra). Since the sequence of metal complexation is such
      that the first three metal ions always bind to the three macrocycles of L(1) and
      L(2) and the fourth to the tren unit, it is possible to prepare heteronuclear
      complexes such as [Cu(3)NiL](8+) or [Ni(3)CuL](8+), which can be unambiguously
      identified by their spectral properties.

PMID- 15249948
TI  - Vitamin B12 as an allosteric cofactor; dual fluorescence, hysteresis,
      oscillations and the selection of corrin over porphyrin.
AB  - Studies of the emission spectra of four Co(III) cobinamides (diaquo-, aquohydroxo
      , dihydroxo- and dicyano-) show (1) that the excited states corresponding to the
      alphabeta and epsilon absorption bands behave like the S(1) and S(2) levels in
      the non-alternant hydrocarbon azulene (with emission from S(2)>> S(1) in
      violation of Kasha's rule) and (2) that the excited states include a TICT
      (twisted intramolecular charge transfer) mechanism, as in the simpler cyanines,
      but where the TICT state gives rise to dual fluorescence instead of cis-trans
      isomerisation. Combined with the previously reported dual fluorescence from the
      S(1) level in synthetic metal corrinoids and in the naturally-occurring metal
      free corrin, this provides evidence that the existence of an additional
      (metastable) ground state with a significantly different vibronic splitting and
      nuclear configuration is an intrinsic property of the basic corrin ligand
      (irrespective of the nature of the side-chains and the metal ion or even the
      absence of a metal) which distinguishes it from porphyrin. The occurrence of
      hysteresis (and its associated oscillations) in redox reactions of the
      cobinamides involving both the Co(III/II) and Co(II/I) couples indicates that the
      corrin ligand also has an intrinsic ability to exist in different conformations
      or "allosteric" forms with differing redox potential, which further distinguishes
      it from the porphyrin ligand. Possible links between the existence of an
      additional metastable ground state and of allosteric changes and the likely
      reasons for the selection of corrin over a porphyrin for the vitamin B(12)
      dependent enzymes are discussed.

PMID- 15249949
TI  - Insights into the absorption of carbon dioxide by zinc substrates: isolation and
      reactivity of di- and tetranuclear zinc complexes.
AB  - The heptadentate Schiff base H(3)L can react with zinc acetate to form the
      discrete dinuclear complex Zn(2)L(OAc)(H(2)O), 1.H(2)O. The reaction of 1.H(2)O
      with NMe(4)OH.5H(2)O both in air and under an argon stream has been investigated.
      On one hand, this reaction in air yields the tetranuclear complex
      (Zn(2)L)(2)(CO(3))(H(2)O)(6), 2.5H(2)O, by spontaneous absorption of adventitious
      carbon dioxide. This process can be reverted in an acetic acid medium, whereas
      the treatment of 2.5H(2)O with methanoic acid yields crystals of
      [Zn(2)L(HCOO)].0.5MeCN.1.25MeOH.2H(2)O, 3.0.5MeCN.1.25MeOH.2H(2)O. On the other
      hand, the interaction under an argon atmosphere of 1.H(2)O with NMe(4)OH.5H(2)O
      in methanol allows the isolation of the dinuclear complex Zn(2)L(OMe)(H(2)O)(4),
      4.4H(2)O. Recrystallisations of 1.H(2)O, 2.5H(2)O and 4.4H(2)O, in different
      solvents, yielded single crystals of 1.MeCN.2.5H(2)O, 2.4MeOH and 4.3MeOH.H(2)O,
      respectively. The crystal structure of 2.4MeOH can be understood as resulting
      from an unusual asymmetric tetranuclear self-assembly from two dinuclear units,
      and shows three different geometries around the four zinc atoms.

PMID- 15249950
TI  - Structure of the hydrated, hydrolysed and solvated zirconium(IV) and hafnium(IV)
      ions in water and aprotic oxygen donor solvents. A crystallographic, EXAFS
      spectroscopic and large angle X-ray scattering study.
AB  - The tetrameric hydrolysis products of zirconium(IV) and hafnium(IV), the
      zirconyl(IV) and hafnyl(IV) ions, [M(4)(OH)(8)(OH(2))(16)(8+)], often labelled
      MO(2+).5H(2)O, are in principle the only zirconium(IV) and hafnium(IV) species
      present in aqueous solution without stabilising ligands and pH larger than zero.
      These complexes are furthermore kinetically very stable and do not become
      protonated even after refluxing in concentrated acid for at least a week. The
      structures of these complexes have been determined in both solid state and
      aqueous solution by means of crystallography, EXAFS and large angle X-ray
      scattering (LAXS). Each metal ion in the [M(4)(OH)(8)(OH(2))(16)](8+) complex
      binds four hydroxide ions in double hydroxo bridges, and four water molecules
      terminally. The M-O bond distance to the hydroxide ions are markedly shorter, ca.
      0.12 A, than to the water molecules. The hydrated zirconium(IV) and hafnium(IV)
      ions only exist in extremely acidic aqueous solution due to their very strong
      tendency to hydrolyse. The structure of the hydrated zirconium(IV) and
      hafnium(IV) ions has been determined in concentrated aqueous perchloric acid by
      means of EXAFS, with both ions being eight-coordinated, most probably in square
      antiprismatic fashion, with mean Zr-O and Hf-O bond distances of 2.187(3) and
      2.160(12) A, respectively. The dimethyl sulfoxide solvated zirconium(IV) and
      hafnium(IV) ions are square antiprismatic in both solid state and solution, with
      mean Zr-O and Hf-O bond distances of 2.193(1) and 2.181(6) A, respectively, in
      the solid state. Hafnium(IV) chloride does not dissociate in N,N'
      dimethylpropyleneurea, dmpu, a solvent with good solvating properties but with a
      somewhat lower permittivity (epsilon= 36.1) than dimethyl sulfoxide (epsilon=
      46.4), and an octahedral HfCl(4)(dmpu)(2) complex is formed.

PMID- 15249951
TI  - Dynamic NMR properties of DOTA ligand: variable pH and temperature 1H NMR study
      on [K(HxDOTA)](3-x)- species.
AB  - The (1)H NMR spectra of [H(x)DOTA]((4-x)-) species are reported as a function of
      pH and temperature in aqueous solution. The spectra show line broadening both in
      ligand proton signals and also in the water proton signal by titration with KOH
      solution. The formation of different [K(H(x)DOTA)]((3-x)-) complexes is found to
      be responsible for this behaviour. At high pH the usual fluxional motions, i.e.
      the ring inversion and the change in the acetate arms' helicity, which are also
      characteristic for other but inert metal-DOTA complexes, have been detected.
      However, because of the kinetic lability of K(+)-O and K(+)-N coordinative bonds
      a new type of rearrangement appears. This new motion requires breaking of
      coordinative bonds in the complex and can be described as a certain type of "ring
      slewing" around the ring C-C bonds. At low temperature (about 270 K) the ring
      slewing slows down and becomes negligible compared with the ring inversion and
      the change in the arms' helicity. These two latter processes have the same rate.
      When the temperature is higher (about 320 K) the ring slewing accelerates and its
      rate exceeds the rate of ring inversion. At this temperature the change in the
      acetate arms' helicity has the same rate as the ring slewing. Additionally, in
      the pH range 4-5 a slow intermolecular proton exchange process has been observed
      between the water and the dissociable protons of [K(H(x)DOTA)]((3-x)-). A water
      assisted proton exchange mechanism is proposed on the basis of the activation
      parameters. This finding supports the previously suggested slow proton motion
      hypothesis for the formation of DOTA complexes.

PMID- 15249952
TI  - Dimetallic complexes of acyclic pyridine-armed ligands derived from 3,6
      diformylpyridazine.
AB  - A bis(pyridine-armed) acyclic Schiff base ligand L1 has been synthesised from 3,6
      diformylpyridazine and two equivalents of 2-(2-aminoethyl)pyridine. Reduction of
      this ligand using NaBH(4) resulted in the formation of the amine analogue L2.
      Complexes of the form [M(2)L1(mu-X)]Y(2)ClO(4)[where: M = Cu(II), X = OH(-) and Y
      = ClO(4)(-) 1, Cl(-) 2, Br(-) 3 or I(-) 4; M = Co(II), X = OH(-) and Y = ClO(4)(
      ) 5; M = Ni(II), X = SCN(-) 6 or X = N(3)(-) 7 and Y = ClO(4)(-)], and
      [Cu(2)L2(mu-OH)](ClO(4))(3) 8 were prepared and characterised. The complexes 1
      and 5-7 have been characterised by single-crystal X-ray diffraction. The acyclic
      L1 ligand provides three nitrogen donor atoms per metal centre, including a
      pyridazine bridge between the metal centres, and the anion X also bridges the two
      metal centres. As required, coordinating solvent molecules or additional anions
      make up the remainder of the coordination sphere. The two copper centres of 1 are
      very strongly antiferromagnetically coupled (2J=-1146 cm(-1))via the pyridazine
      and hydroxide ion bridges, whereas the competing antiferromagnetic pyridazine
      bridging pathway and ferromagnetic 1,1-bridging azide pathway resulted in the
      observation of weak antiferromagnetic exchange in the dinickel(II) complex 7 (2J=
      14 cm(-1)). Electrochemical examination of L1, L2 and complexes 1 and 5-8
      revealed multiple redox processes. These have been tentatively assigned to a
      mixture of metal centred and ligand centred redox processes on the basis of
      cyclic voltammetry and coulometry results and comparisons with literature
      examples.

PMID- 15249953
TI  - Open, cyclic, and bicyclic compounds of double silylated phosphorus and boron.
AB  - Salt elimination reactions of tris(trimethylsilyl)silyl potassium (1), and two
      1,4-dipotassiooligosilanes (3, 5) with 2,2,6,6
      tetramethylpiperidinodichloroborane and diethylaminodichlorophosphane have
      generated open (2), cyclic (4) and bicyclic (6) bora- and phosphaoligosilanes. A
      monosilylated phosphane and the two five-membered cyclosilanes have been
      subjected to single crystal X-ray diffraction analysis.

PMID- 15249954
TI  - Singularity of proton transport in salts of orthoperiodic and orthotellurium
      acids: theoretical modeling using density functional calculations.
AB  - Density functional B3LYP calculations have been performed to investigate proton
      transport in orthoperiodic and orthotellurium acids, their salts MIO(6)H(4)(M =
      Li, Rb, Cs) and CsH(5)TeO(6), dimers of the salt*acid type MIO(6)H(4)*H(5)IO(6)(M
      = Rb, Cs), CsIO(6)H(4)*H(6)TeO(6), CsHSO(4)*H(6)TeO(6), Cs(2)SO(4)*H(6)TeO(6),
      and also in double-substituted and binary salts Rb(2)H(3)IO(6) and
      Rb(4)H(2)I(2)O(10). It has been shown that the energy of salt dimerization is 33
      35 kcal mol(-1) and the activation barrier for proton migration between the
      neighboring octahedrons of the salt*acid --> acid*salt type is calculated to be 3
      13 kcal mol(-1). The activation energy of the proton migration along the
      octahedron, 20-30 kcal mol(-1), is comparable with the barrier for water molecule
      separation. Quantum-chemical calculations correlate with the results of X-ray and
      electrochemical studies.

PMID- 15249955
TI  - A fluorescent chemosensor for Zn(II). Exciplex formation in solution and the
      solid state.
AB  - The macrocyclic phenanthrolinophane 2,9-[2,5,8-triaza-5-(N-anthracene-9
      methylamino)ethyl]-[9]-1,10-phenanthrolinophane (L) bearing a pendant arm
      containing a coordinating amine and an anthracene group forms stable complexes
      with Zn(II), Cd(II) and Hg(II) in solution. Stability constants of these
      complexes were determined in 0.10 mol dm(-3) NMe(4)Cl H(2)O-MeCN (1:1, v/v)
      solution at 298.1 +/- 0.1 K by means of potentiometric (pH metric) titration. The
      fluorescence emission properties of these complexes were studied in this solvent.
      For the Zn(II) complex, steady-state and time-resolved fluorescence studies were
      performed in ethanol solution and in the solid state. In solution, intramolecular
      pi-stacking interaction between phenanthroline and anthracene in the ground state
      and exciplex emission in the excited state were observed. From the temperature
      dependence of the photostationary ratio (I(Exc)/I(M)), the activation energy for
      the exciplex formation (E(a)) and the binding energy of the exciplex (-DeltaH)
      were determined. The crystal structure of the [ZnLBr](ClO(4)).H(2)O compound was
      resolved, showing that in the solid state both intra- and inter-molecular pi
      stacking interactions are present. Such interactions were also evidenced by UV
      vis absorption and emission spectra in the solid state. The absorption spectrum
      of a thin film of the solid complex is red-shifted compared with the solution
      spectra, whereas its emission spectrum reveals the unique featureless exciplex
      band, blue shifted compared with the solution. In conjunction with X-ray data the
      solid-state data was interpreted as being due to a new exciplex where no pi
      stacking (full overlap of the pi-electron cloud of the two chromophores -
      anthracene and phenanthroline) is observed. L is a fluorescent chemosensor able
      to signal Zn(II) in presence of Cd(II) and Hg(II), since the last two metal ions
      do not give rise either to the formation of pi-stacking complexes or to exciplex
      emission in solution.

PMID- 15249956
TI  - Lithium alkyl assisted coupling of a 2-cyano-2,3-dihydro-1H-1,3,2-diazaborole to
      give tBuNCH=CHN(tBu)BC(iPr)=N-BN(tBu)CH=CHNtBu.
AB  - Reaction of 2-cyano-1,3,2-diazaborole tBuNCH=CHN(tBu)BCN (2) with half an
      equivalent of isopropyllithium afforded compound tBuNCH=CHN(tBu)BC(iPr=N
      BN(tBu)CH=CHNtBu (7). In contrast to this, a 1:1 stoichiometry of the reactants
      led to tBuNCH=CHN(tBu)BiPr (6) as the product of a nucleophilic substitution
      process at the boron atom. Similarly, regardless of the molar ratio of reactants
      employed, treatment of 2 with cyclopropyllithium, isobutyllithium or
      phenyllithium afforded solely substitution products tBuNCH=CHN(tBu)BR [R =cPr
      (12); Ph (13); iBu (14)].

PMID- 15249957
TI  - Models for biological trinuclear copper clusters. Characterization and
      enantioselective catalytic oxidation of catechols by the copper(II) complexes of
      a chiral ligand derived from (S)-(-)-1,1'-binaphthyl-2,2'-diamine.
AB  - The dinuclear and trinuclear Cu(II) complexes of an octadentate ligand derived
      from (S)-1,1'-binaphthyl-2,2'-diamine have been prepared and characterized by
      UV/Vis, CD, EPR and NMR spectroscopy. The ligand contains two tridentate
      aminobis(benzimidazole) donor arms connected to a central bidentate
      diaminobinaphthyl linker, which hosts the chiral unit. In the dinuclear Cu
      complex the ligation occurs essentially within the tridentate arms of the ligand.
      The two Cu centers are EPR nonequivalent and noninteracting. The EPR data
      suggests that one of the Cu ions additionally interacts with one of the tertiary
      aminonaphthyl donors. In the trinuclear complex the two aminonaphthyl donors bind
      the third Cu ion. The EPR spectrum of this complex shows the signal for a
      mononuclear Cu(II) center bound to a tridentate arm, while the remaining two
      Cu(II) centers are coupled through hydroxo groups. The CD spectrum shows that in
      the free ligand a severe reduction of the dihedral angle between the naphthyl
      groups from the strain free range occurs. This conformation is stabilized by ring
      stacking interactions with the benzimidazole groups. On complex formation this
      interaction is removed because the benzimidazole groups are involved in metal
      binding. In the dinuclear Cu complex the conformation of the binaphthyl
      chromophore probably approaches the strain free range, while in the trinuclear Cu
      complex a marked flattening of the dihedral angle between the two naphthyl rings
      occurs. Both complexes are active catalysts in the oxidation of L-/D-Dopa
      derivatives to quinones. High enantioselectivity is observed in the oxidation of
      L-/D-Dopa methyl ester catalyzed by the dinuclear Cu complex, which exhibits
      strong preference for the d enantiomer. The enantioselectivity is largely lost
      for the trinuclear Cu complex.

PMID- 15249958
TI  - Influence of organic bases on constructing 3D photoluminescent open metal-organic
      polymeric frameworks.
AB  - Four three-dimensional non-interpenetrating open coordination frameworks
      constructed from the CTC ligand (CTC =cis,cis-1,3,5-cyclohexanetricarboxylate)
      coordinated to metal ions (Mn(II) and Cd(II)): Mn(3)(CTC)(2)(DMF)(2)(1);
      Cd(3)(CTC)(2)(H(2)O)(3).H(2)O (2); Cd(3)(CTC)(2)(4,4'-bpy)(2)(EG)(2)(3);
      Cd(3)(CTC)(2)(mu(2)-hmt)(DMF)(C(2)H(5)OH)(H(2)O).2H(2)O (4)(DMF =
      dimethylformamide and EG = ethylene glycol) have been synthesized by slow
      evaporation of DMF-C(2)H(5)OH-H(2)O solutions of M(II)(Mn(II) or Cd(II)) and CTC
      in the presence of the organic bases TEA (triethylamine), TEA, 4,4'-bpy (4,4'
      bipyridine) and hmt (hexamethylenetetramine), respectively, and structurally
      characterized by X-ray crystallography. The polymer constructed by CTC and Mn(II)
      exhibits a 3-D architecture with 5 x 9 A channels; the polymer formed by CTC and
      Cd(II) exists a 3-D extended framework with 9 x 9 A channels; wave-like sheet
      subunits of the polymer are upheld by 4,4'-bpy ligands resulting in a 3-D
      framework with 4 x 10 A channels; two-fold alternate sheet subunits of the
      polymer are interlinked by mu(2)-hmt ligands to form a novel 3-D architecture
      with 7 x 8 A channels. Polymers exhibit their strongest excitation peaks at 391,
      390 and 394 nm, respectively, and their main strong emission peaks are at 543,
      460 (with a shoulder peak at about 570 nm) and 557 nm, respectively.

PMID- 15249959
TI  - [Urological illnesses in the elderly].
AB  - Urological illnesses in the elderly are a growing clinical problem because as
      life expectancy increases so does the prevalence of such illnesses. However,
      sufficient data for judging the various possible therapies are lacking for
      patients over the age of 70. Age itself does not have enough predictive value for
      the determination of the best treatment. It seems more important to estimate the
      functional and socio-economic status, comorbidity, and the cognitive and
      emotional abilities of elderly patients as well as their nutritional intake.

PMID- 15249960
TI  - [Geriatric assessment. Is it significantly helpful in selection of elderly tumour
      patients for a difficult therapy?].
AB  - With increasing life expectancy, a therapeutic decision raises the question of
      the primary goals to be aimed for. Is an absolute gain in age a goal equal to the
      preservation of an active life? While in younger patients the strategy followed
      by the patient and the doctor will usually be that of long-term survival, the
      decision making process for older patients with functional deficits is more
      challenging. Though functional deficits show a positive correlation with age, a
      causal relationship does not exist, which implies considerable inter-individual
      heterogeneity in the group of older patients. In particular, patients who have
      reached older ages "successfully" without any major limitations in their health
      should be considered for more intensive treatment strategies. At the same time,
      younger patients with relevant functional limitations and without any chance of
      improvement may not benefit from these interventions. The comprehensive geriatric
      assessment (CGA) offers the opportunity to describe and classify these deficits
      systematically. It therefore has a key role in the individual decision making
      process.

PMID- 15249961
TI  - [Liver transplantation in elderly patients].
AB  - Since the first liver transplantation (OLT) was performed by Starzl in 1963, this
      has become the standard therapy for end stage chronic liver disease and acute
      hepatic failure. It is also the therapy of choice in selected cases of hepatic
      malignancy. Due to the optimization of intra- and perioperative management, new
      immunosuppressant drugs and improved organ procurement, the clinical outcome in
      patient and graft survival has increased continuously. The shortage of donor
      organs has led to the development of new surgical techniques such as split- and
      living related transplantation. OLT should also be offered to elderly patients.
      Careful evaluation and patient selection results in good patient and graft
      survival after transplantation, which is comparable to that in with younger
      recipients.

PMID- 15249962
TI  - [Kidney donors and kidney transplantation in the elderly].
AB  - The likelihood of terminal renal insufficiency escalates with age, increasing the
      risk of dying as a patient requiring dialysis. In 1999, Eurotransplant initiated
      the Eurotransplant Senior Programm (ESP), in which the kidneys of old donors (>64
      years) are allocated to recipients 64 years and older. Allocation does not take
      HLA-matching into account and is performed regionally only according to blood
      group-compatibility to keep the storage time short. As a consequence of the short
      ischemic time, and thus reduced non-immunological damage to the anyways
      susceptible old kidney, graft-function and graft-survival in the ESP are very
      good. The results of the initial 5 years of this program show that it
      successfully utilizes more kidneys from old donors and that more old recipients
      are being transplanted, with a satisfactory graft-function. Increased donor-
      and/or recipient age require a thorough evaluation to exclude malignant and other
      diseases. Furthermore, short term controls on the waiting list and following
      kidney transplantation are prerequisites for successful transplantation in the
      aged recipient. If this is guaranteed, kidney transplantation in the old
      recipient-even with old donor organs-is a good alternative to the morbidity of a
      prolonged dialysis. Nevertheless, the role of HLA-matching should be reconsidered
      to reduce rejections.

PMID- 15249963
TI  - [The prevalence of sexual problems in female medical students].
AB  - Female sexual dysfunction and even female sexual function are widely unknown. We
      therefore evaluated the sexual behaviour of younger and older women using a
      questionnaire. A total of 998 young women entered the study at Hannover Medical
      school. They were between 19 and 43 years old (median 24 years), and 64% answered
      the questionnaire. A total of 97.1% of the female students were heterosexual,
      1.6% were lesbians and 1.3% were bisexual. Lack of sexual intercourse in the
      previous month was recorded by 21.1%, while 21.3% recorded intercourse 1-3 times
      a month, 46.8% 1-3 times a week and 5.5% daily. Adverse reactions to sexual
      situations were reported by 25% of the women, 20.5% had a negative perception for
      special partners or circumstances. Some 55% of the evaluated women were satisfied
      with their sexual life in the last month, 20% were fairly satisfied and 21% were
      un-satisfied. This study of a selected population of medical students shows a
      wide variety of sexual problems with a high prevalence of different disorders.

PMID- 15249964
TI  - [False aneurysm and bleeding caused by a secondary dislocated lesser trochanter
      fragment].
AB  - A 92-year-old woman incurred an unstable pertrochanteric hip fracture with
      avulsion of the lesser trochanter (type 31-A2 according to the AO
      classification). The fracture was treated by gliding nail osteosynthesis, without
      fixing the minimally displaced lesser trochanter. No intra- or postoperative
      complications were detected. Suddenly, after 30 days, a swelling of the proximal
      femoral region, accompanied by signs of haemorrhage, occurred.CT-scans showed a
      false aneurysm of the deep femoral artery and a dorsal laceration of the artery
      proximal to the aneurysm. X-rays showed a further dislocation with rotation of
      the lesser trochanter fragment. Intraoperatively, the tip of the lesser
      trochanter fragment was identified to be responsible for the laceration of the
      artery. The false aneurysm was resected and the defect bridged by a vascular
      prosthesis while the fragment was removed. Follow-up showed no further
      complications. According to case reports from the literature, false aneurysms and
      laceration of the deep femoral artery caused by dislocated lesser trochanter
      fracture fragments are rare.

PMID- 15249965
TI  - [Operative management of cervical spine injuries in patients with Bechterew's
      disease].
AB  - Cervical spinal injuries in patients with ankylosing spondylitis are complex in
      their nature and management. This condition is associated with a high risk of
      dislocation and neurological impairment related to osseous instability due to
      almost absent compensatory mechanisms of the adjacent vertebral segments.
      Multilevel stabilization and dorsoventral instrumentation is usually required. We
      report on two patients suffering from ankylosing spondylitis who presented at our
      institute with cervical spine injuries in whom primary treatment had consisted of
      single-site stabilization which resulted in secondary fracture dislocation and
      implant failure. Secondary management by combined dorsoventral stabilization
      resulted in more rigid fixation and uneventful healing in both cases. We
      recommend careful assessment and well-planned management in these cases.

PMID- 15249966
TI  - [Squamous cell carcinomas of the upper aerodigestive tract. Prognostic
      significance of the capsular rupture and extracapsular spread of lymph node
      metastases].
AB  - The capsular rupture and subsequent extranodal spread of lymph node metastases is
      of crucial and well established prognostic value in patients with squamous cell
      carcinomas of the upper aerodigestive tract. Besides the basic histologic
      definition of the extranodal spread (i.e. contact of the metastasis with
      perinodal fatty tissue), there is no agreement on the morphologic extent of
      transcapsular spread. As a measure of improvement, a histologic evaluation
      differentiating between seven gradual types of metastatic nodal affection was
      applied. The histologic scheme considers intranodal growth, infiltration of the
      capsule, the presence of desmoplasia and especially the rupture of the capsule
      and the subsequent extranodal spread of the metastasis. As extranodal spread is
      an easily reproducible and reliably significant prognostic criterion, it should
      be included in the current TNM classification, e.g., by an addition of the index
      R+ (lymph node metastasis with capsular rupture) or R- (lymph node metastasis
      without capsular rupture) to the N category.

PMID- 15249967
TI  - [Differential diagnosis of soft tissue sarcomas].
AB  - INTRODUCTION: Soft tissue sarcoma often goes undetected. PATIENTS AND METHODS:
      Over a 10-year period, the patients referred to us with a soft tissue tumor (STT)
      of the extremities and wall of the trunk were analyzed retrospectively. The aim
      of the present study was to investigate the differential diagnoses, the number of
      incompletely operated STS, and local recurrences together with their percentage
      fluctuations. RESULTS: A total of 490 patients with an STT were referred to our
      department, and of these patients 55% were diagnosed with an STS. In addition to
      STS, the differential diagnoses for STT included 2% lymphomas, 18% isolated
      carcinoma metastases, 18% benign mesenchymal tumors, 5% inflammatory processes,
      and 2% old hematomas. Only 45% of the STS had not undergone previous surgery. Of
      these, 15% had been incompletely resected, while 39% of the STS patients were
      admitted with a local recurrence. Within the 10-year period, referrals with STT
      and STS remained relatively constant, but referrals of patients with incompletely
      resected or recurrent STS doubled in the last 2 years under observation.
      DISCUSSION: In view of the numerous differential diagnoses of an STT, both the
      possibility of an STS and also carcinoma manifestations in the soft tissues
      should receive more attention. With the aim of reducing the relatively high
      number of STS re-resections and local recurrences, the treatment of patients with
      suspicious STT should be reserved for a specialized center.

PMID- 15249968
TI  - [Multimedia preoperative patient information].
AB  - Due to heavy workloads and shortage of staff, doctors often find it difficult to
      explain operations to their patients with the legally required detail and timing
      (in Germany, 24 h preop). This is however mandatory for obtaining informed
      consent. We developed a computer program that generates films explaining 24
      common orthopedic operations and blood transfusion. They explain the operation,
      early postoperative phase, and benefits and risks to the patient. At our clinic,
      this program is used in daily routine and precedes the actual doctor-patient
      conversation for informed consent. We asked 300 patients about their satisfaction
      with the newly developed program. The multimedia presentation gives the patient
      more time, enough detail and clarity, and the chance to repeat parts of the film.
      For the doctor, it saves time. The time gap required in Germany between
      explanation and operation is thus easily adhered to. In case of legal problems,
      the film can be used for evidence. The use of this multimedia presentation to
      help in getting informed consent is improving workflow considerably.

PMID- 15249969
TI  - [Suicidal fatal beta-blocker intoxication].
AB  - We report on the case of a 45-year-old female with beta receptor antagonist
      intoxication after swallowing about 30 tablets of Cordanum (Talinolol) with
      suicidal intent. The out of hospital and clinical management is discussed. Prior
      to admission to hospital the patient only showed a few signs of intoxication such
      as hypotension, central symptoms and cyanosis. There was no bradycardia but
      during treatment she developed cardiac arrest. Out of hospital it was possible to
      stabilise the circulation with catecholamines (norepinephrin) and the transport
      to hospital was uneventful but only a few minutes after hospital admission the
      patient developed cardiac arrest. After initially successful CPR the patient died
      some hours later in the intensive care unit.

PMID- 15249970
TI  - The application of multi-parameter flow cytometry to the study of recombinant
      Escherichia coli batch fermentation processes.
AB  - Multi-parameter flow cytometric techniques coupled with dual colour fluorescent
      staining were used to study the physical and metabolic consequences of inclusion
      body formation in batch cultures of the recombinant Escherichia coli strain
      MSD3735. This strain contains a plasmid coding for the
      isopropylthiogalactopyranoside-inducible model eukaryotic protein AP50. It is
      known that the synthesis of foreign proteins at high concentrations can exert a
      severe metabolic stress on the host cell and that morphological changes can
      occur. In this work, using various points of induction, it was shown that
      inclusion body formation is followed immediately by measurable changes in the
      characteristic intrinsic light scatter patterns for the individual cell (forward
      scatter, 90 degrees side scatter) and a concomitant progressive change in the
      individual cell physiological state with respect to both cytoplasmic membrane
      polarisation and permeability. This work establishes flow cytometry as a
      potentially valuable tool for monitoring recombinant fermentation processes,
      providing important information for scale-up. Further, we discuss the possibility
      of optimising inclusion body formation by manipulating the fermentation
      conditions based on these rapid "real-time" measurements.

PMID- 15249971
TI  - Influence of zero flow pressure on fractional flow reserve.
AB  - Fractional flow reserve (FFR) is a commonly used index to assess the functional
      severity of a coronary artery stenosis. It is conventionally calculated as the
      ratio of the pressure distal (Pd) and proximal (Pa) to the stenosis (FFR= Pd/Pa).
      We hypothesize that the presence of a zero flow pressure (Pzf), requires a
      modification of this equation. Using a dynamic hydraulic bench model of the
      coronary circulation, which allows one to incorporate an adjustable Pzf, we
      studied the relation between pressure-derived FFR = Pdo/Pa, flow-derived true
      FFRQ = Qs/QN (= ratio of flow through a stenosed vessel to flow through a normal
      vessel), and the corrected pressure-derived FFRc = (Pd-Pzf)/(Pa-Pzf) under
      physiological aortic pressures (70 mmHg, 90 mmHg, and 110 mmHg). Imposed Pzf
      values varied between 0 mmHg and 30 mmHg. FFRc was in good agreement with FFRQ,
      whereas FFR consistently overestimated FFRQ. This overestimation increased when
      Pzf increased, or when Pa decreased, and could be as high as 56% (Pzf=30 mmHg and
      Pa =70 mmHg). According to our experimental study, calculating the corrected FFRC
      instead of FFR, if Pzf is known, provides a physiologically more accurate
      evaluation of the functional severity of a coronary artery stenosis.

PMID- 15249972
TI  - Effect of liver fatty acid binding protein (FABP) T94A missense mutation on
      plasma lipoprotein responsiveness to treatment with fenofibrate.
AB  - Fenofibrate, a peroxisome proliferated activated receptor alpha (PPARalpha)
      agonist, has been shown to decrease plasma triglyceride (TG) and increase plasma
      high-density lipoprotein (HDL) cholesterol levels despite a large interindividual
      variation in the response. Fenofibrate-activated PPARalpha binds to a DNA
      sequence element termed PPAR response element (PPRE) present in regulatory
      regions of target genes. A PPRE has been identified in the proximal 5' flanking
      region of the gene encoding the liver fatty acid binding protein (LFABP). LFABP
      is a small cytosolic protein of 14 kDa present in the liver and the intestine and
      is a member of the superfamily of the fatty acid binding proteins (FABPs). FABPs
      play a role in the solubilization of long-chain fatty acids (LCFAs) and their CoA
      ester to various intracellular organelles. FABPs serves as intracellular
      acceptors of LCFAs, and they may also have an impact in ligand-dependent
      transactivation of PPARs in trafficking LCFAs to the nucleus. Since PPARs are
      known to regulate the transcription of many genes involved in lipid metabolism,
      the importance of LFABP in fatty acid uptake has to be considered. The aim of
      this study was to verify whether genetic variations in the LFABP gene may impact
      on plasma lipoprotein/lipid levels in the fasting state as well as on the
      response to a lipid-lowering therapy with fenofibrate on plasma lipids and
      obesity variables. We also wanted to verify whether the presence of the PPARalpha
      L162V mutation interacts with genetic variants in LFABP gene. To achieve this
      goal, we first determined the genomic structure of the human LFABP gene and then
      designed intronic primers to sequence the coding regions, all exon-intron
      splicing boundaries, and the promoter region of the gene in 24 patients showing
      divergent plasma lipoprotein/lipid response to fenofibrate. Sequence analysis
      revealed the presence of a T94A missense mutation in exon 3. Interspecies
      comparison revealed that threonine 94 is conserved among species. We subsequently
      screened another sample of 130 French Canadian subjects treated with fenofibrate
      for the presence of the LFABP T94A mutation. Carriers of the A94 allele were at
      increased risk to exhibit plasma TG levels above 2.00 mmol/l after treatment with
      fenofibrate [2.75 (1.03-7.34); OR 95% confidence interval (CI)]. In addition,
      carriers of the A94 allele were characterized by higher baseline plasma-free
      fatty acid levels (FFA) ( p=0.01) and by a lower body mass index (BMI) ( p=0.05)
      and waist circumference ( p=0.005) than T94 homozygotes. Moreover, PPARalpha
      L162V and LFABP T94A showed to have a synergistic effect on BMI ( p interaction =
      0.03). These results suggest that the LFABP T94A missense mutation could
      influence obesity indices as well as the risk to exhibit residual
      hypertriglyceridmia following a lipid-lowering therapy with fenofibrate.

PMID- 15249973
TI  - The white-phase-specific gene WH11 is not required for white-opaque switching in
      Candida albicans.
AB  - Phenotypic switching between white and opaque cells is important for adaptation
      to different host environments and for mating in the opportunistic fungal
      pathogen Candida albicans. Genes that are specifically activated in one of the
      two cell types are likely to be important for their phenotypic characteristics.
      The WH11 gene is a white-phase-specific gene that has been suggested to be
      involved in the maintenance of the white-phase phenotype. To elucidate the role
      of WH11 in white-opaque switching, we constructed mutants of the C. albicans
      strain WO-1 in which the WH11 gene was deleted. The Delta wh11 mutants were still
      able to form both white and opaque cells whose cellular and colony phenotypes
      were indistinguishable from those of the wild type. Deletion of WH11 also did not
      affect the activation and deactivation of the white-phase-specific WH11 promoter
      and the opaque-phase-specific OP4 and SAP1 promoters in the appropriate cell
      type. Finally, switching from the white to the opaque phase and vice versa
      occurred with the same frequency in wild-type and Delta wh11 mutants. Therefore,
      the WH11 gene is not required for phenotypic switching, and its protein product
      seems to have other roles in white cells, which are dispensable after the switch
      to the opaque phase.

PMID- 15249974
TI  - Immunolocalization of myosin Va in the developing nervous system of embryonic
      chicks.
AB  - Myosins are molecular motors associated with the actin cytoskeleton that
      participate in the mechanisms of cellular motility. During the development of the
      nervous system, migration of nerve cells to specific sites, extension of growth
      cones, and axonal transport are dramatic manifestations of cellular motility. We
      demonstrate, via immunoblots, the expression of myosin Va during early stages of
      embryonic development in chicks, extending from the blastocyst period to the
      beginning of the fetal period. The expression of myosin Va in specific regions
      and cellular structures of the nervous system during these early stages was
      determined by immunocytochemistry using a polyclonal antibody. Whole mounts of
      chick embryos at 24-30-h stages showed intense immunoreactivity of the neural
      tube in formation along its full extent. Cross-sections at these stages of
      development showed strong labeling in neuroepithelial cells at the basal and
      apical regions of the neural tube wall. Embryos at more advanced periods of
      development (48 h and 72 h) showed distinctive immunolabeling of neuroepithelial
      cells, neuroblasts and their cytoplasmic extensions in the mantle layer of the
      stratified neural tube wall, and neuroblasts and their cytoplasmic extensions in
      the internal wall of the optic cup, as well as a striking labeling of cells in
      the apparent nuclei of cranial nerves and budding fibers. These
      immunolocalization studies indicate temporal and site-specific expression of
      myosin Va during chick embryo development, suggesting that myosin Va expression
      is related to recruitment for specific cellular tasks.

PMID- 15249975
TI  - The development of the proximal oesophageal pouch in the adriamycin rat model of
      oesophageal atresia with tracheo-oesophageal fistula.
AB  - This study examined the morphological development of the proximal oesophagus in
      the Adriamycin-induced rat model of oesophageal atresia. The proximal oesophageal
      segment in oesophageal atresia with tracheo-oesophageal fistula (OA?TOF) has been
      assumed to be of similar embryological origin to the distal oesophagus. However,
      recent research using the Adriamycin model of OA?TOF has indicated that these
      structures may have a different origin. Time-mated Sprague-Dawley rats were
      administered either Adriamycin intraperitoneally or saline of an equivalent
      volume between days 6-9 of gestation. The rats were sacrificed between days 11-19
      of gestation, their embryos removed and histologically sectioned. These sections
      were analysed to observe the morphological changes occurring in the proximal
      foregut. The proximal oesophageal pouch first appeared on day 15.25 as a dorsal
      outpouching of the proximal foregut immediately cranial to an area of apoptosis
      in the dorsal epithelium of the distal pharynx. It elongated through a process of
      cellular proliferation until it was clearly formed on day 16. Relatively little
      growth occurred from days 17-19. In the rat developing oesophageal atresia, the
      proximal oesophageal pouch has an origin different to that of the distal
      oesophagus. This study may explain the difference in immunohistological
      properties and intrinsic nervous supply between the proximal and distal
      oesophageal segments in oesophageal atresia.

PMID- 15249976
TI  - Magnetic resonance imaging of obstetrical brachial plexus injuries.
AB  - OBJECTIVE: We reviewed MR imaging in infants with Erb's palsy. The goal was to
      determine the effectiveness of MR imaging in predicting operative findings for
      these infants. METHODS: Fifteen patients (mean age: 14.5 months) underwent
      surgical exploration of the brachial plexus. Preoperative MR imaging was acquired
      in all patients with a GE (Milwaukee, WI, USA) 1.5-Tesla MRI and correlated with
      the surgical findings as outlined in the children's operative notes. RESULTS:
      Through imaging, the presence of at least one pseudomeningocele was found in 8 of
      the 15 patients (53.3%) while 3 of the 15 patients (20%) had multiple
      pseudomeningoceles. Posterior shoulder subluxation was seen in 11 patients
      (73.3%). Fourteen children(93.3%) had imaging abnormalities consistent with
      either a reparative neuroma or scar tissue investing plexus elements. We were
      unable to differentiate between the two with MR imaging. At surgery, scar tissue
      was found entrapping the C5-C6 roots, upper trunk, and/or lateral and posterior
      cords in 11 patients (73.3%)while 4 patients had reparative neuromas. Two
      patients had both entrapment by scar tissue and a reparative neuroma. Either
      entrapment by scar tissue or neuroma was found in all 15 patients (100%).
      CONCLUSIONS: MR imaging is an effective tool for demonstrating lesions of the
      brachial plexus worthy of surgical exploration.

PMID- 15249978
TI  - [Problems for ophthalmologists in the certification of blindness ].
AB  - BACKGROUND: We compared the medical test results of 117 persons examined by the
      superintendent for blindness assessment in 2002 with their certificates of
      blindness (5.5% of the applications, 42% of the testimonial examinations
      performed in Hessen in 2002). METHODS: If the ratings as "blind" or "severely
      visually handicapped" (corresponding to a visual acuity of not more than 0.02 or
      0.05, resp.) differed between the medical test and the certificate, visual
      acuity, visual field, further findings, and the methods of assessment were
      analyzed on the basis of the medical records. RESULTS: The medical test confirmed
      75 certificates. Fourteen persons with a certificate of blindness were graded as
      severely visually handicapped by the medical test. In 8 and 12 cases,
      respectively, the criteria of neither blindness nor severe visual handicap were
      fulfilled. Eight persons with a certificate of severe visual handicap were graded
      as blind by the medical test. DISCUSSION: In 29% of the cases, the visual
      handicap did not reach the certified grade. Striking differences occurred between
      the certificate and the functions shown in the medical test. In the certificates,
      the declared visual handicap was regularly judged to correspond to the objective
      findings, but apparently in these cases symptom validity had not been critically
      assessed. An improvement of diagnostic validity could be achieved using
      relatively uncomplicated subjective and objective tests.

PMID- 15249979
TI  - Cost-analysis of staging methods for lymph nodes in patients with prostate
      cancer: MRI with a lymph node-specific contrast agent compared to pelvic lymph
      node dissection or CT.
AB  - The aim of this study was to compare the costs of three strategies in patients
      with prostate cancer in a specific setting: firstly, a strategy including MR
      lymphography (MRL) in which pelvic lymph node dissection (PLND) is foregone in
      case of a negative result. The second strategy involves computed tomography (CT)
      followed by a biopsy or PLND. The third strategy consists of PLND without imaging
      beforehand. A decision analytic model was constructed. This model represented the
      diagnostic process for patients with prostate cancer and intermediate or high
      risk for nodal metastases, comparing the costs of the three strategies. Cost
      analysis was done from the health care perspective. The model indicated that the
      expected costs for the MRL strategy were 2,527 euro. The expected costs for the
      strategy using CT were 3,837 euro and for PLND 3,994 euro. These results show
      that potential savings performing MRL instead of CT were 1,310 euro and 1,467
      euro for PLND. Sensitivity analyses show that variation in costs of PLND was most
      influential on the costs of all strategies. However, the overall savings pattern
      did not alter. Average costs of MRL staging in our institution are less than for
      CT and PLND in staging lymph nodes of patients with prostate cancer and who are
      intermediate or high risk for nodal metastases.

PMID- 15249980
TI  - Radiological placement of chest ports in pediatric oncology patients.
AB  - A single center's procedural and follow-up results of radiological chest port
      placement in pediatric oncology patients are presented. Between July 2002 and
      December 2003, 37 children (20 boys, 17 girls; age range, 4 months to 16 years;
      mean 6.7 years) underwent chest port placement. All patients received only one
      port through the internal jugular vein access, and all of the implantations were
      performed in the interventional radiology suite. Our database and electronic
      charts were retrospectively reviewed to obtain follow-up data. All chest ports
      were successfully implanted. The mean catheter life was 223 days (range: 15-450
      days), with a total of 8,258 catheter days. Twenty-eight ports are still in use,
      four patient deceased, one port was prematurely removed because of a late
      infection, and four patients were lost to follow-up. Infection rate was 2.7%
      (0.12/1,000 catheter days). Malfunction due to partial catheter thrombosis and
      fibrin sheath formation was observed in three patients (8.1% or 0.36/1,000
      catheter days), and all were relieved with rt-TPA dwell. None of the ports were
      revised or removed because of blockage, malposition or difficulty accessing the
      port. The peri-procedural complication rate was 0%. Chest ports in children can
      be inserted in interventional radiology suites under imaging guidance with high
      rates of technical success. The rates of infection and complications are
      comparable to that of surgically placed ports.

PMID- 15249981
TI  - Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents
      in vitro.
AB  - To evaluate the capacity of human monocytes to phagocytose various approved iron
      oxide based magnetic resonance (MR) contrast agents and to optimize in vitro
      labeling of these cells. Human monocytes were incubated with two
      superparamagnetic iron oxide particles (SPIO) as well as two ultrasmall SPIO
      (USPIO) at varying iron oxide concentrations and incubation times. Iron uptake in
      monocytes was proven by histology, quantified by atomic emission absorption
      spectrometry and depicted with T2* weighted fast field echo (FFE) MR images at
      1.5 T. Additionally, induction of apoptosis in iron oxide labeled monocytes was
      determined by YO-PRO-1 staining. Cellular iron uptake was significantly (P<0.01)
      higher after incubation with SPIO compared with USPIO. For SPIO, the iron oxide
      uptake was significantly (P<0.01) higher after incubation with the ionic
      Ferucarbotran as compared with the non-ionic Ferumoxides. Efficient cell labeling
      was achieved after incubation with Ferucarbotran at concentrations > or = 500
      microg Fe/ml and incubation times > or = 1 h, resulting in a maximal iron oxide
      uptake of up to 50 pg Fe/cell without impairment of cell viability. In vitro
      labeling of human monocytes for MR imaging is most effectively obtained with the
      approved SPIO Ferucarbotran. Potential subsequent in vivo cell tracking
      applications comprise, e.g. specific targeting of inflammatory processes.

PMID- 15249982
TI  - Protein-losing enteropathy associated with systemic lupus erythematosus: response
      to cyclophosphamide.
AB  - Protein-losing enteropathy is a rare manifestation of systemic lupus
      erythematosus (SLE) leading to hypoalbuminemia and anasarca. We report the case
      of a woman with SLE who presented chronic hypoalbuminemia diagnosed as protein
      losing enteropathy associated with SLE. She was refractory to prednisone and
      azathioprine administration but showed good response to cyclophosphamide. The
      diagnosis and management of hypoalbuminemia in lupus-associated enteropathy are
      discussed.

PMID- 15249983
TI  - The demise of chloroplast DNA in Arabidopsis.
AB  - Although it might be expected that chloroplast DNA (cpDNA) would be stably
      maintained in mature leaves, we report the surprising observation that cpDNA
      levels decline during plastid development in Arabidopsis thaliana (Col.) until
      most of the leaves contain little or no DNA long before the onset of senescence.
      We measured the cpDNA content in developing cotyledons, rosette leaves, and
      cauline leaves. The amount of cpDNA per chloroplast decreases as the chloroplasts
      develop, reaching undetectable levels in mature leaves. In young cauline leaves,
      most individual molecules of cpDNA are found in complex, branched forms. In
      expanded cauline leaves, cpDNA is present in smaller branched forms only at the
      base of the leaf and is virtually absent in the distal part of the leaf. We
      conclude that photosynthetic activity may persist long after the demise of the
      cpDNA.

PMID- 15249984
TI  - An esophago-atrial vein or fibrous cord in a top fold of the oblique sinus of the
      pericardial sac.
AB  - In a previous anatomical study of the oblique sinus of pericardium, we reported
      on the morphological variations of this recess. We noted a previously undescribed
      variation of its top in 32.7% of our cases. Here we detail this variation using
      microscopic and macroscopic mediastinal dissections of 107 adult fresh cadavers.
      It seems a top fold of the oblique sinus contains a permeable esophago-atrial
      vein or a fibrous cord. These unique variations of the oblique sinus modify the
      classical anatomical and embryological descriptions. Abnormal esophago-atrial
      veins have not been described previously but they are predictable according to
      embryological knowledge. From a clinical point of view, such a vein, permeable or
      not, may facilitate extension of esophageal carcinoma to the pericardium and may
      represent a porto-systemic bypass in cases of portal hypertension.

PMID- 15249985
TI  - MR appearance of SONK-like subchondral abnormalities in the adult knee: SONK
      redefined.
AB  - OBJECTIVE: To investigate the MR characteristics of SONK-like (spontaneous
      osteonecrosis of the knee) subchondral abnormalities in the adult atraumatic knee
      and to recategorize these patients into two subgroups: a subacute to chronic
      process associated with osteoarthritis and an acute process associated with
      insufficiency fractures. DESIGN: We retrospectively examined the knee MRIs of 39
      patients with non-specific interpretations of osteochondral abnormalities.
      PATIENTS: There were a total of 52 subchondral lesions without any known
      traumatic event and no prior surgery. All lesions evaluated had MR features
      previously ascribed to SONK. Several MR characteristics were then assessed:
      presence or absence of a line, size, zonal location, T1 and T2 signal, associated
      marrow edema, associated ipsilateral meniscal tear, and associated ipsilateral
      cartilage defects. RESULTS AND CONCLUSIONS: The abnormalities with linear
      components (insufficiency fractures) tended to be larger (P<0.01) and were
      associated with a severe amount of marrow edema (P<0.0001) consistent with an
      acute process. The non-linear abnormalities were more associated with cartilage
      defects (P=0.01) and less marrow edema consistent with osteoarthritis and a
      subacute to chronic process. This association of SONK-like abnormalities with
      osteoarthritis and insufficiency fractures casts doubt on the validity of the
      term "spontaneous osteonecrosis" as it is currently applied, and further
      investigation into the separate etiologies of these subchondral marrow lesions is
      needed.

PMID- 15249986
TI  - Limitation of apoptotic changes in renal tubular cell injury induced by
      hyperoxaluria.
AB  - Renal tubular epithelium is the major target for oxalate induced injury, and
      sustained hyperoxaluria together with CaOx crystal formation/deposition may
      induce renal tubular cell damage and/or dysfunction. This may express itself in
      cell apoptosis. To evaluate the possible protective effects of certain agents
      (vitamin E, potassium citrate, allopurinol, verapamil and MgOH) on the presence
      and the severity of apoptotic changes caused by hyperoxaluria on renal tubular
      epithelium, an experimental study in rabbits was performed. Seventy rabbits were
      divided into seven different groups (each group n = 10): in group I severe
      hyperoxaluria was induced by continuous ethylene glycol (0.75%) administration
      started on day 0 and completed on day 14. Histologic alterations including
      crystal formation together with apoptotic changes (by using the TUNEL method)
      were evaluated on days 21 and 42, respectively. In the remaining experimental
      groups (groups II-VI), animals received some agents in addition to the induction
      of hyperoxaluria in an attempt to limit apoptotic changes. Group VII) animals
      constituted the controls. Kidneys were examined histopathologically under light
      microscopy for the presence and degree of crystal deposition in the tubular
      lumen. The percentage of apoptotic nuclei in the control group was significantly
      different from the other group animals (2.9-2.4%) in all study phases (P < 0.05).
      Apart from potassium citrate and allopurinol, the other medications seemed to
      prevent or limit the formation of apoptotic changes in renal tubular epithelium
      during the early period (day 21). The percentage of positively stained nuclei in
      animals undergoing potassium citrate medication ranged from 24.3% to 28.6%, with
      an average of 27.1%. This was 18.4% in animals receiving allopurinol. On the
      other hand, animals receiving magnesium hydroxide (MgOH), verapamil and vitamin E
      demonstrated limited apoptotic changes (11.2, 9.7, 8.7%, respectively) during
      this phase(P < 0.05). In the long-term (day 42), the animals receiving
      allopurinol and vitamin E showed a decrease in the percentage of the positively
      stained nuclei (13.5% and 8.3%, respectively). Animals in the other groups showed
      an increase in the number and percentage of apoptotic cells. Although, there was
      a significant decrease in the mean values of apoptosis in animals receiving
      vitamin E (8.7%-8.3%) and allopurinol (18.4%-13.5%) (P < 0.05), animals on
      verapamil, MgOH and potassium citrate medication had an increase in these values
      or the change was not found to be significant. In the light of our findings and
      results from the literature, it is clear that that both hyperoxaluria and CaOx
      crystals may be injurious to renal epithelial cells. Apoptotic changes observed
      in renal tubular epithelial cells induced by massive hyperoxaluria might result
      in cell degradation and may play a role in the pathologic course of urolithiasis.
      Again, as demonstrated in our study, the limitation of both crystal deposition
      and apoptotic changes might be instituted by some antioxidant agents as well as
      urinary inhibitors. Clinical application of such agents in the prophylaxis of
      stone disease might limit the formation of urinary calculi, especially in
      recurrent stone formers.

PMID- 15249987
TI  - Behavioral studies of auditory-visual spatial recognition and integration in
      rats.
AB  - Rodents are useful animal models in the study of the molecular and cellular
      mechanisms underlying various neural functions. For studying behavioral
      properties associated with multisensory functions in rats, we measured the speed
      and accuracy of target detection by the reaction-time procedure. In the first
      experiment, we utilized simple two-alternative-choice tasks, in which spatial
      cues are visual or auditory modalities, and conducted a cross-modal transfer test
      in order to determine whether rats recognize amodal spatial information. Rats
      showed successful performance in the cross-modal transfer test and the speed to
      respond to sensory stimuli was constant under a rule-consistent condition despite
      the change in cue modality. In the second experiment, we developed audiovisual
      two-alternative-choice tasks, in which both auditory and visual stimuli were
      simultaneously presented but one of the two modalities was task-relevant, in
      order to determine whether the response to the sensory stimulation of one
      modality is enhanced by the stimulation of a different modality. If bimodal
      stimuli were spatially coincident, the speed for detecting the relevant stimulus
      was shortened and the extent of the effect was comparable to those in past
      studies of humans and other mammals. These results indicate the cross-modal
      spatial abilities of rats and our present paradigms may provide useful behavioral
      tasks for studying the neural bases of multisensory processing and integration in
      rats.

PMID- 15249988
TI  - Responses of dorsal subicular neurons of rats during object exploration in an
      extended environment.
AB  - The subiculum receives a direct projection from the perirhinal cortex, a cortical
      area whose neurons are responsive to the novelty or familiarity of objects
      encountered in the environment. We made recordings of subicular neuronal activity
      while male adult Wistar rats conducted object exploration tasks, which have been
      previously shown to cause changes in the exploratory behaviour of rats and which
      are dependent upon the integrity of structures within the hippocampal formation.
      In the current study, the exploratory behaviour of the rats was also modified in
      a manner consistent with them perceiving the novelty and familiarity of the
      objects used as part of the apparatus. Subicular cell firing, however, appeared
      to correlate best not with object novelty or familiarity, but with the concurrent
      location and speed of the rats within the task environment. These findings are
      discussed in light of previously reported 'object-responsive' subicular firing
      correlates.

PMID- 15249989
TI  - Different effects of fatiguing exercise on corticospinal and transcallosal
      excitability in human hand area motor cortex.
AB  - Following forceful exercise that leads to muscle fatigue, the size of muscle
      evoked responses (MEPs) generated by transcranial magnetic stimulation (TMS) in
      the exercised muscle is depressed over a prolonged period. Strong evidence
      implicates intracortical mechanisms in this depression. As well as evoking MEPs
      in contralateral muscles, TMS also reduces MEPs evoked in ipsilateral muscles
      through interhemispheric inhibition mediated by a transcallosal pathway. Here we
      have sought to determine whether this effect is also depressed after exercise.
      Using two magnetic stimulators, the aftereffects of unilateral hand muscle
      exercise on the ability of TMS delivered to the hemisphere that generated the
      exercise were examined to i) generate MEPs in the exercised hand muscles, and ii)
      depress MEPs evoked by TMS pulses in contralateral (non-exercised) hand muscles.
      After exercise there was a significant reduction in the amplitudes of MEPs evoked
      by TMS in the exercised muscles ( p<0.001). However, the same stimuli remained
      able to depress responses evoked by TMS to the contralateral hemisphere in the
      non-exercised muscles as effectively as before the exercise. We conclude that
      unlike the MEPs evoked by corticospinal output, interhemispheric inhibition
      evoked from the hemisphere that generated the exercise is not depressed after
      exercise. A similar differential effect on interhemispheric inhibition and
      corticospinal output has been reported recently for the effects of transcranial
      direct current (DC) stimulation of the motor cortex. Fatiguing exercise and
      transcranial DC stimulation may therefore engage similar intracortical
      mechanisms.

PMID- 15249990
TI  - Measurement of total selenium and selenium(IV) in seawater by stripping
      chronopotentiometry.
AB  - We developed a stripping chronopotentiometric method (constant current stripping
      analysis, CCSA) with a mercury film electrode for selenium quantification in
      seawater. A sensitivity and detection limit of 222 ms ng(-1) l and 4 ng l(-1) (50
      pM), respectively, were accomplished for a 3-min electrolysis time. Compared to
      the other chronopotentiometric methods available for a single selenium
      measurement only in natural waters, our procedure exhibits a ten times better
      sensitivity. It, therefore, allows one to reach the current concentration
      thresholds found in coastal and oceanic waters (30-200 ng l(-1)). Moreover, a
      simple change in operating conditions enables one to also quantify Se(IV), a
      toxic dissolved species. With respect to the other electrochemical methods of
      current use, our procedure is beneficial because of its ease-of-use: it needs
      neither degassing step, nor catalyser.

PMID- 15249993
TI  - Analysis of gene expression profiles of forestomach tumors in rasH2 mice
      initiated with N-ethyl-N-nitrosourea.
AB  - To clarify the mechanisms underlying enhancement of carcinogenesis in transgenic
      mice carrying a human prototype c-Ha- ras gene (rasH2 mouse), animals received a
      single intraperitoneal injection of 120 mg/kg N-ethyl-N-nitrosourea (ENU) and at
      20 weeks thereafter expression profiles in three induced forestomach squamous
      cell carcinomas were assessed using high-density oligonucleotide microarrays. In
      addition, the reverse transcriptase-polymerase chain reaction (RT-PCR) was
      performed to assess mRNA expression of human c-Ha- ras gene and some molecules
      involved in the Ras-regulated mitogen-activated protein kinase (MAPK) pathway.
      Compared with normal forestomach tissue from control mice, 416 and 368 genes,
      respectively, were found to be commonly up- and down-regulated by 2-fold or more
      in the three tumors. Many genes involved in tumor invasion and metastasis such as
      transforming growth factor beta1 and matrix metalloproteinases were up-regulated,
      reflecting tumor progression. RT-PCR analysis confirmed up-regulation of
      transgene, mouse endogenous Ha- ras, N- ras, raf, Mekk2, c- fos, junB, c- myc and
      cyclin D1. These results suggest that activation of the Ras-MAPK cascade
      following up-regulation of both human and mouse endogenous ras genes is involved
      in the enhanced tumorigenesis of ENU-induced forestomach squamous cell carcinomas
      in rasH2 mice.

PMID- 15249992
TI  - Changes in c-fos expression in the rat heart during morphine withdrawal.
      Involvement of alpha2-adrenoceptors.
AB  - We previously demonstrated an increase in Fos expression in the heart during
      morphine withdrawal. In the present study we examined the role of beta- and alpha
      adrenoceptors in naloxone-precipitated increases in Fos expression in the heart.
      Dependence on morphine was induced by 7-day chronic subcutaneous implantation of
      six morphine pellets (75 mg). Morphine withdrawal was precipitated by
      administration of naloxone (5 mg/kg subcutaneously) on day 8. Using
      immunohistochemical staining of Fos, the present results indicate that morphine
      withdrawal induced marked Fos immunoreactivity (Fos-IR) within the cardiomyocyte
      nuclei. Moreover, Western blot analysis revealed a peak expression of c-fos in
      the right and left ventricles after naloxone-precipitated withdrawal in parallel
      with an increase in noradrenaline (NA) turnover. In the second study, the effects
      of the administration of adrenoceptor antagonists on withdrawal-induced Fos
      expression in the heart were studied. Pretreatment with the beta antagonist,
      propranolol (3 mg/kg intraperitoneally) or alpha1-adrenoceptor antagonist,
      prazosin (1 mg/kg intraperitoneally) did not block the marked Fos-IR or the
      hyperactivity of catecholaminergic neurons observed in the heart during
      withdrawal. However, pre-treatment with alpha2-adrenoceptor antagonist, yohimbine
      (1 mg/kg intraperitoneally), 20 min before naloxone administration to morphine
      dependent rats antagonized Fos expression and the enhancement of NA turnover in
      the heart. Collectively, these results suggest that noradrenergic neurons in the
      heart are active during morphine withdrawal, and that activation of
      transcriptional responses mediated by Fos are dependent upon cardiac alpha2
      adrenoceptor.

PMID- 15249991
TI  - Implications of genetic research on the role of the serotonin in depression:
      emphasis on the serotonin type 1A receptor and the serotonin transporter.
AB  - Serotonin systems appear to play a key role in the pathophysiology of major
      depressive disorder. Consequently, ongoing research determines whether serotonin
      related genes account for the very robust differential behavioral and neural
      mechanisms that discriminate patients with depression from healthy controls.
      Serotonin type 1(A) receptors and the serotonin transporters are reduced in
      depression, and recent genetic research in animals and humans has implicated both
      in depression. Preclinical studies have utilized a variety of animal models that
      have been used to explain pathophysiological mechanisms in humans, although it is
      not clear at all whether these models constitute relevant models for depression
      in humans. However, data from preclinical studies can generate hypotheses that
      are tested in humans by combining genetic data with behavioral and physiological
      challenge paradigms and neuroimaging. These studies will enhance our
      understanding about combined influences from multiple interacting genes, as well
      as from environmental factors on brain circuits and their function, and about how
      these mechanisms may contribute to the pathophysiology of neuropsychiatric
      disorders.

PMID- 15249994
TI  - Induced hypothermia in traumatic brain injury: considering the conflicting
      results of meta-analyses and moving forward.

PMID- 15249995
TI  - Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in
      Type 1 diabetes and insulin sensitivity.
AB  - AIMS/HYPOTHESIS: Beta cell loss in Type 1 and Type 2 diabetes mellitus may result
      from apoptosis and necrosis induced by inflammatory mediators. The suppressor of
      cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and
      also influences insulin signalling. SOCS3 could therefore be a candidate gene in
      the development of Type 1 and Type 2 diabetes mellitus. METHODS: Mutation
      analysis of the SOCS3 gene was performed in 21 patients with Type 1 diabetes
      mellitus and in seven healthy subjects. An identified promoter variant was
      examined in (i) 250 families with Type 1 diabetic family members (1097
      individuals); (ii) 212 glucose-tolerant first-degree relatives of Type 2 diabetic
      patients; and (iii) 370 population-based young, healthy subjects who were
      unrelated. RESULTS: Three mutations were identified in the promoter region, but
      none in the coding region or the 3'UTR. Two of the three mutations had allele
      frequencies below 1% whereas the C -920-->A substitution had a minor allele
      frequency of 8%. In the group of young healthy subjects the insulin sensitivity
      index was higher among homozygous carriers of the A-allele than among
      heterozygous and wild-type subjects ( p=0.027, uncorrected). The same trend was
      found in the group of first-degree relatives of Type 2 diabetic patients. No
      association or linkage was found to Type 1 diabetes mellitus.
      CONCLUSIONS/INTERPRETATION: Homozygosity for the A-allele of the C -920-->A
      promoter polymorphism of the SOCS3 gene may be associated with increased whole
      body insulin sensitivity, but deserves further investigation.

PMID- 15249996
TI  - Towards worldwide standardisation of HbA1c determination.
AB  - Haemoglobin A(1)c (HbA(1)c) or glycohaemoglobin is one of the most important
      parameters in the management of patients with diabetes mellitus, but to date
      there is no international standard for determining HbA(1)c. Most of the routine
      HbA(1)c assays are standardised against one of the local standardisation schemes
      like the NGSP (USA) and other schemes (Japan, Sweden). Still, results of HbA(1)c
      tests diverge considerably, as do the accompanying clinical decision limits. The
      IFCC Working Group on HbA(1)c Standardisation has developed a reference method
      and also set up a reference system for HbA(1)c, in which the analyte is defined
      as beta-N-glycated haemoglobin. This reference system consists of a network of
      reference laboratories that uses the reference methods and certified reference
      materials for optimal measurement of HbA(1)c in human blood. The main task of the
      network is to assign values to secondary reference materials, to be used by
      manufacturers of routine HbA(1)c assays to calibrate their assays. The high
      specificity of the reference method results in lower HbA(1)c values in blood
      samples, since the unspecific components falsely identified as HbA(1)c in routine
      methods are not measured by the reference method. The reference range for the new
      reference method was determined as 3 to 4% and the clinical decision limits were
      translated from existing guidelines: goal of treatment 5% HbA(1)c, change of
      therapy advised at HbA(1)c greater than 6%. Despite these lower values, worldwide
      implementation of the IFCC reference system for HbA(1)c is recommended, in order
      to end the great divergence in HbA(1)c results, with which physicians and
      patients are confronted today.

PMID- 15249997
TI  - Loss of beta cell function as fasting glucose increases in the non-diabetic
      range.
AB  - AIMS/HYPOTHESIS: Our aim was to define the level of glycaemia at which pancreatic
      insulin secretion, particularly first-phase insulin release, begins to decline.
      METHODS: Plasma glucose and insulin concentrations were measured during an IVGTT
      in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the
      men C-peptide was also estimated. IVGTT insulin secretion in first and late
      phases was assessed by: (i) the circulating insulin response; (ii) population
      parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a
      combined model utilising both insulin and C-peptide concentrations. Measurements
      of insulin sensitivity and elimination were also derived by modelling analysis.
      RESULTS: As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin
      secretion declined by 73%, 71% and 68% for the three methods respectively. The
      FPG values at which this decline began, determined by change point regression,
      were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase
      insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l.
      Insulin elimination, but not insulin sensitivity, varied with FPG.
      CONCLUSIONS/INTERPRETATION: The range of FPG over which progressive loss of the
      first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase
      insulin responses declining at FPG concentrations above 6.0 mmol/l.

PMID- 15249998
TI  - [Functional results after surface replacement of the hip: comparison between
      dysplasia and idiopathic osteoarthritis].
AB  - AIM: To determine if there are differences in function after resurfacing
      arthroplasty of the hip in patients with primary osteoarthritis compared to
      patients with secondary osteoarthritis due to developmental dysplasia of the hip.
      METHOD: In a controlled prospective study of Birmingham Hip Resurfacing (BHR) we
      included all patients with primary osteoarthritis (n = 54, average age 48.4
      years) and osteoarthritis due to high grade dysplasia (Eftekhar B, n = 34,
      average age 55.8 years). Standardized clinical (Harris hip score) and
      radiographic examinations were performed 6 weeks, 3 months and 6 months and then
      every year after the operation. RESULTS: All patients could be followed up to 1.5
      years (1-4 years) after surgery. The average Harris hip score improved to 82-95
      points in both groups 3 months postoperatively. Statistically significant
      differences could be found in the subscales "function" and "limp", where patients
      with dysplastic hips showed somewhat lower results after 6 (function) to 12 weeks
      (limp) postoperatively. This is probably attributable to extended non-weight
      bearing after acetabular reconstruction in these cases, as the difference
      disappeared with full weight-bearing. Radiographically determined neck-shaft
      angles are slightly higher in dysplastic hips (142 degrees versus 135 degrees ),
      but we did not recognize any significant differences in implant positioning.
      CONCLUSION: The short- to mid-term results showed no clinically relevant
      functional differences after surface replacement in patients with primary
      osteoarthritis of the hip and patients with secondary osteoarthritis due to
      higher grade dysplasia. Long-term observation is necessary, however, to determine
      if these positive functional results are reflected by appropriate radiographic
      survival.

PMID- 15249999
TI  - [Cup placement in hip replacement surgery -- A comparison of free-hand and
      computer assisted cup placement in total hip arthroplasty -- a multi-center
      study].
AB  - AIM: The purpose of the current study was to determine the accuracy of free hand
      and computer-assisted (CAS) cup placement. MATERIAL AND METHODS: Between June
      1985 and August 2001, 105 free-hand and from March to November 1999 80 total hip
      arthroplasties under computer assistance were implanted in the above mentioned
      centers. To determine the accuracy of the cups, the inclination and anteversion
      angles were measured. In all cases the cup position was measured with a CT
      investigation of the pelvis. Statistical analysis was performed with the F-test.
      RESULTS: With regard to the inclination and anteversion angles the variability of
      the cup position was significantly higher in the group of free hand implanted
      cups. In the CAS group we could not find any "extreme" positions. CONCLUSION:
      Using computer-assisted surgery a significantly higher reproducible cup position
      can be obtained. Long time survey may present a lowering of the rate of early and
      late complications caused by better prostheses alignment in the follow up.

PMID- 15250000
TI  - [Long-term results of uncemented Parhofer-Monch screw rings].
AB  - AIM: The aim of this study was an analysis of the long-term behaviour and implant
      migration of the Parhofer-Monch-screw cup seen in patients between 1982 and 1991.
      METHOD: 92 cups (m : f = 53 : 39, mean age 53 +/- 7 years) were included mainly
      prospectively. After 118 +/- 45 months all patients were examined clinically and
      radiologically. Digital migration analysis was performed using the single-film X
      ray analysis (Einbildrontgenanalyse, EBRA). RESULTS: 5 patients had died. 32 cups
      were revised, in 7 patients a loosening of the cup was suspected. The 10-year
      survival was 71.4 %. In 53 of 81 analysed cups a migration of more than 1 mm was
      shown, 28 cups did not migrate. In comparison to these stable implants the
      survival of migrated cups was significantly inferior. CONCLUSION: The 10-year
      survival and the high rate of implant migration document the poor results of the
      PM cup. In spite of an extraordinary primary stability, the failure of secondary
      osseointegration represents the main cause of loosening in this type of cup.

PMID- 15250001
TI  - [The cement free hollow hip prosthesis to reduce intramedullary pressure].
AB  - PURPOSE: A hollow cementless femoral stem has been developed to reduce
      intramedullary pressure and fat embolism during implantation. METHODS: In a
      prospective randomized clinical study, cementless hip stems (ALPHA-FIT) were
      implanted in 42 patients (24 women, 18 men, mean age: 65.9 years). In Group I
      (n=21) a solid standard stem was used. In Group II (n=21) a modified hollow stem
      was implanted with vertical and longitudinal communicating drill holes opening at
      the implant surface. During surgery the intramedullary pressure was measured by a
      cannula fixed distally. RESULTS: During stem insertion the mean pressure was 82
      mmHg (minimum-maximum, 12-259 mmHg) for Group I and 27 mmHg (minimum-maximum, 0
      48 mmHg) for Group II. This difference was statistically significant (t-test, p <
      0.00076). The pressure measured in Group II was similar to the base pressure
      before opening of the intramedullary canal (mean 35 mmHg; minimum-maximum, 4-72
      mmHg). In both groups higher pressures were found for opening of the canal,
      drilling with the smallest drill size and rasping. CONCLUSION: Using the hollow
      prosthesis, the intramedullary pressure could be reduced significantly. The
      higher pressures during preparation of the femoral canal need further research.

PMID- 15250002
TI  - [Primary rotatory stability of hip endoprostheses stems after manual and robot
      assisted implantation].
AB  - AIM: In our study we compared the primary rotatory stability of hip
      endoprostheses which were implanted with the help of a robot with that of
      manually implanted stems. METHOD: We examined three different types of prosthesis
      stems: Osteolock (Stryker-Howmedica), CBC (Mathys), Excia (Aesculap).
      Furthermore, we examined two types of prostheses which could not be implanted
      with a robot (Sl-Plus/Endoplus; Hipstar/Stryker-Howmedica). 10 stems of each
      prosthesis type were implanted in identical polyurethane foam blocks; 5 of them
      were implantated manually, 5 with the help of a robot (CASPAR, URS-Ortho). After
      implantation, a defined rotatory stress was put on the stem with the help of a
      torquing machine. The torsional moment which was necessary until the stem broke
      out of the foam was documented with the help of special software. RESULTS: In all
      types of prostheses the use of the robot system led to a higher rotatory
      stability compared to the manual group. Among the three tested types of
      prosthesis stems, the CBC stem is significantly more stable for rotatory forces
      after robot-assisted implantation compared to the other two types. After manual
      implantation there was no difference in stability between the different stems.
      The Zweymuller stem and the Hipstar prosthesis did very well, even in comparison
      to the robot-implanted group. The results of the Zweymuller stem and the robot
      implanted CBC Stem were similar, and a significantly higher rotatory stability of
      the Hipstar prosthesis compared to every other stem was observed. CONCLUSION:
      Using a robot, the rotatory stability of hip endoprostheses can be improved.
      However, the design of the stems seems to be even more important for the
      stability than the implantation technique.

PMID- 15250003
TI  - [The primary stability between manual and robot assisted implantation of hip
      prostheses: A biomechanical study on synthetic femurs].
AB  - AIM: We investigated the initial stability of cementless stems implanted with
      robotic milling and conventional manual broaching. METHODS: Proximally porous
      structured stems (G2, ESKA-Implants, Luebeck, Germany) were implanted into
      synthetic femora. In one group, the femoral cavity was prepared by a CT-based
      robot (CASPAR, URS-Ortho, Germany) with a high-speed milling head. In the other
      group, femora were rasped manually with broaches. The broaches had 1 mm proximal
      press-fit, the robotic cavities 1.5 mm. The implants were exposed to 15 000
      loading cycles with 1 000 +/- 500 N. The direction of forces on the implant head
      were chosen to simulate stair climbing. Internal rotation and translation
      (caudal, dorsal and lateral) of the implants were measured by linear transducers.
      RESULTS: The robotic group showed significantly less reversible motion regarding
      translation in caudal, dorsal and lateral directions. The standard deviations of
      implant motions were smaller in the robotic group. CONCLUSION: Using robotic
      preparation of the femur, initial stability was higher and more consistent than
      with manual broaching, but differences in undersizing of the cavities created in
      the femur in relation to the implant may have contributed to these differences
      for the most part. In-vitro-loading experiments focusing on femoral cavities with
      varying press-fits are recommended before the introduction of new implants or
      operating procedures.

PMID- 15250004
TI  - [The cement-free modular revision prosthesis MRP-hip revision stem prosthesis in
      clinical follow-up].
AB  - INTRODUCTION: We present prospective medium-term results of the modular revision
      prostheses "MRP-TITANIUM". MATERIAL AND METHODS: 45 patients (n = 48 prostheses)
      were evaluated. The mean follow-up was 4.7 years (min.-max.: 1.0-9.0 years). Pre-
      and postoperatively the Harris hip score (differentiated to Paprosky I-III) was
      examined. 66.67 % of the cases had extensive bony defects (> or = Paprosky II b).
      By means of X-ray examinations, the stability of the prostheses, periprosthetic
      bone remodelling, the presence of radiolucent lines as well as bone defect
      regeneration were assessed postoperatively. RESULTS: The mean Harris hip score
      improved from 25.6 preoperative to 71.4 postoperative (p < or = 0.05). In 44
      cases the X-ray showed stable fixation without secondary migration. In one case
      the stem (stand time 2.36 years) was revised due to secondary migration (> or = 5
      mm). The survival rate (Kaplan-Meier) was 97 %. Bone transplantation with
      consecutive defect regeneration was (n = 30) complete in all cases. In six cases
      (12.5 %) a postoperative dislocation occurred with subsequent successful closed
      reposition four times (8.3 %). In two cases (4.2 %) an open reposition was done
      with correction of the antetorsion angle of the prostheses. CONCLUSION: The "MRP
      TITANIUM modular revision prostheses" has proved to be reliable in cases of
      revision surgery with extensive bony defects. The failure rate was 2.1 % for 48
      prospectively examined prostheses.

PMID- 15250005
TI  - [Radiological appearance of the cementless ALLOCLASSIC SL-stem implanted in very
      old patients with primary hip osteoarthritis].
AB  - AIM: The radiological appearance of the cementless ALLOCLASSIC SL-stem, implanted
      in patients with primary osteoarthritis of the hip and aged at least 80 years at
      time of surgery, was investigated. METHOD: 66 hips in 58 patients were analysed.
      17 patients (19 hips) died in the interim, 5 patients (5 hips) were not available
      for follow-up because of health reasons (4) or lack of co-operation (1). 1 stem
      had to be explanted after a periprosthetic fracture of the femur. Finally, 41
      total hip arthroplasties in 35 patients could be analysed after an average of
      67.9 months (39.2-93.4). RESULTS: Bone atrophy - especially in the proximal Gruen
      zones - was frequently found. In contrast, radiolucent lines and osteolyses were
      rare occurrences. The Harris Hip score was preoperatively on average 33.0 points,
      at time of follow-up 81.7 points. The survival rate (endpoint aseptic loosening)
      was 100 % after a mean follow-up of 5.7 years. CONCLUSION: Also in very old
      patients the implantation of a cementless stem is possible and provides very good
      results.

PMID- 15250006
TI  - [Can the number of thromboembolisms incidents in total hips replacement be
      further reduced?].
AB  - QUESTION: Is it possible to reduce the rate of thrombembolic events during total
      hip arthroplasty (THA) by the intraoperative use of a mechanical device for
      thrombembolic prophylaxis (A-V Impulse System). METHOD: The efficacy of
      additional mechanical thrombembolic prophylaxis was investigated in a prospective
      randomised trial on 104 patients who underwent cementless THA. All patients
      received low dose heparin. In 52 patients the additional application of the A-V
      Impulse System was introduced intraoperatively for the next 24 h. A perfusion
      scintigram of the lung was performed before and 7 days after the operation in
      both groups to detect embolic patterns. RESULTS: Perfusion deficits typical for
      thromboembolic events were detected postoperatively in 8 patients (15.4 %) of the
      controls and 5 patients (9.6 %) of the A-V Impulse System group. CONCLUSIONS:
      With the perfusion lung scan we saw postoperatively a total of 13 patients (12.5
      %, n=104) with an asymptomatic microthromboembolism of the lungs. Hence it is
      necessary to increase the protection against thromboembolism. Although
      statistically not significant (p=0.374), there is a tendency that the additional
      use of the mechanical thrombotic prophylaxis can reduce thromboembolic events in
      THA. The impact of the intraoperative introduction of the A-V Impulse System is
      not really clear. However, for a higher velocity of blood flow during the
      operation it makes sense to start the procedure intraoperatively.

PMID- 15250007
TI  - [Soft tissue reconstruction following total knee arthroplasty: treatment
      possibilities and retrospective analysis of plastic surgery therapy treatment
      possibilities].
AB  - AIM: We performed a retrospective analysis of patients with soft tissue defects
      following total knee arthroplasty and therapy. Furthermore, we described the
      possibilities of covering soft tissue defects following knee arthroplasty.
      METHOD: In 5 patients, soft tissue defects following knee arthroplasty were
      covered with medial M. gastrocneminus flaps. Localisation and size of the defect,
      microbiology, risk factors, and interval between arthroplasty and the occurrence
      of the soft tissue defect were retrospectively analysed. RESULTS: On average,
      defects occurred 9 weeks after prosthesis implantation. In all cases, the soft
      tissue defect developed in the area of the incision. In 3 cases, wound infection
      was diagnosed. Four patients exhibited factors associated with wound-healing
      failure. No prosthesis was lost. CONCLUSION: The gastrocneminus muscle flap
      provides good quality coverage with small donor site defect, permits early
      mobilisation, and allows for fast rehabilitation. The risk of flap loss is
      minimal. Early and adequate defect coverage can reduce both prosthesis loss and
      amputation rates.

PMID- 15250008
TI  - [Infection diagnosis after knee-TEP-implantation].
AB  - AIM: In this study, the accuracy of antigranulocyte scintigraphy as a diagnostic
      means prior to revision in infected total knee replacement was compared to that
      of preoperative joint aspiration and laboratory parameters. The most efficient
      combination of all diagnostic methods was calculated and thus a diagnostic
      algorithm recommended. The value of PCR was compared to commonly used techniques
      of microbiological culturing. METHODS: Preoperative diagnostic means for
      infection of 50 total knee replacements in 45 patients requiring revision
      surgery, were retrospectively analyzed. Inclusion criteria were the
      intraoperative microbiological and histological verification of infection.
      Sensitivity, specificity, negative and positive prediction value of C-reactive
      protein (CRP) and leukocytes, antigranulocyte scintigraphy with (99m)Tc-labeled
      antibodies, and preoperative joint aspiration were calculated. Furthermore, the
      accuracy of the different techniques of culturing was compared to that of the
      polymerase chain reaction (PCR) based on the intraoperative histological
      findings. Two blinded examiners evaluated specimens taken intraoperatively
      according to the criteria of Mirra. RESULTS: We observed a sensitivity of 1.0, a
      specificity of 0.82, a positive prediction value of 0.83 and a negative
      prediction value of 1.0 for the antigranulocyte scintigraphy. The sensitivity of
      preoperative joint aspiration was 0.5, the specificity 1.0, and the positive and
      negative prediction values were 1.0 and 0.5. Correlated to the intraoperative
      histological findings the accuracy of PCR and culturing was comparable. The
      highest accuracy was obtained for blood culture samples. CONCLUSION: Compared to
      preoperative joint aspiration the antigranulocyte scintigraphy proved to be more
      sensitive in the diagnosis an infected knee replacement while having a high
      specificity. An advantage of PCR compared to the common microbiological culturing
      techniques was not observed.

PMID- 15250009
TI  - [3D-Culturing of human osteoblastic cells with vessel like nutrient supply].
AB  - AIM: The treatment of large, critical-size bone defects is a major therapeutic
      problem in orthopaedic and reconstructive surgery. The engineering of bone tissue
      could be used to replace lost bone mass. However, scaffolds seeded with vital
      cells and cultured in vitro suffer from poor oxygen and nutrient supply
      centrally, when the constructs exceed a critical volume. Therefore, we have
      established an osteoblastic cell culture in a new 3D-culture chamber with an
      artificial, vessel-like central membrane, allowing continuous nutrient supply.
      METHOD: Human osteoblasts were cultured in a 3D-like manner using a perfusion
      chamber for one week. In this system, the nutrient supply is guaranteed by a
      vessel-like, semipermeable polysulfone membrane with a continuous flow of medium.
      After fixation and cryosectioning, histological and immunohistological staining
      and scanning electron microscopy was carried out. RESULTS: Examinations reveal 3D
      cell growth around the central vessel. Formation of an extracellular matrix, rich
      in collagen type I and fibronectin, was detected immunohistochemically.
      Furthermore, we demonstrated cell adherence to the membrane and examined the
      surface morphology by scanning electron microscopy. CONCLUSION: The innovative
      approach for 3D-culturing of human osteoblasts in a system with a central
      nutrient supply opens up new possibilities for the in vitro cultivation for
      tissue engineering.

PMID- 15250010
TI  - [Biomechanical tests of a new scaffold for the cultivation of chondrocytes].
AB  - AIM: Scaffolds for the cultivation of chondrocytes are of increasing importance.
      So far, only little is known about their biomechanical properties. The present
      preliminary study addresses the biomechanical characteristics of a new collagen
      type I scaffold for the cultivation of chondrocytes. MATERIAL AND METHODS: Human
      chondrocytes were amplified in a monolayer and then cultivated in a 3D-scaffold
      over a period of up to 6 weeks. The biomechanical tests addressed the properties
      under uniaxial compression including stiffness and viscoelastic characteristics
      (creep and retardation). The obtained values were normalized against the
      thickness of the specimens and expressed as ratios. In addition, we present
      histological and quantitative PCR results (for collagen type II and aggrecan).
      RESULTS: The maximum force (or penetration force) revealed its highest values
      after a period of seven days. At this time the median value was 40 mN/mm. In the
      following period, a marked drop of the values was observed (19.8 mN/mm). With
      respect to the creep properties, we did not find any major changes over the
      period of six weeks. The median values were between 0.24 and 0.29 mm/mm. There
      were no significant differences between the samples seeded with chondrocytes and
      those which served as controls. A re-expansion of the samples was found with
      median values between 0.026 and 0.049 mm/mm (retardation). However, the original
      thickness was not reached after a period of 30 seconds with relief of the strain.
      Again, major differences of the values with respect to the duration of
      cultivation were not observed. Light microscopy revealed collagen type II and
      proteoglycans only in the pericellular region. CONCLUSION: In this study not all
      of the biomechanical properties of the cultivated tissue were investigated. The
      limitation of the tests to stiffness and viscoelastic properties was reasonable
      in view of a potential routine use. In addition, it may facilitate a comparison
      between different matrix systems. In our study, the cultivation of cells within
      the collagen matrix did not alter the mechanical properties of the scaffold.

PMID- 15250011
TI  - [Biocompatibility testing of various biomaterials as dependent on immune status].
AB  - INTRODUCTION: This study deals with the ingrowth behaviour of biomaterials
      (hydroxyapatite, cp-titanium, cobalt-chromium-molybdenum and PAEK) in
      relationship to the immunological competence in an animal model. Measured were
      the production of extracellular matrix (ECM) after implantation in non
      immunocompetent naked mice and immunocompetent wild mice. Intention of the trial
      was to find out if either the immunological competence or the duration of
      implantation influences the quantity of produced ECM. In addition, the ingrowth
      behaviour was investigated under these conditions by using four different
      biomaterials. MATERIAL AND METHODS: Biomaterials (hydroxyapatite, cp-titanium,
      cobalt-chromium-molybdenum and PAEK) were implanted for 14 or 60 days,
      respectively. CLSM, SEM and SEM-EDX were used for analysis of the ECM and for
      measuring the distance between ECM and the biomaterials. CLSM was also used for
      the detection of collagen I and III as a parameter of the quality of
      osteointegration. RESULTS: In all cases a matrix grew on the surface of the
      biomaterials. The CLSM detected a co-localisation of collagen I and III. In the
      case of hydroxyapatite collagen I and III were found at a distance of 1 micro m
      over the surface. The largest space between the surface of the implant and the
      ECM was found in the case of PAEK. The smallest space was in the case of
      hydroxyapatite. In all investigated biomaterials the proportion of collagen I to
      collagen III varied through the duration of implantation. DISCUSSION: As is known
      from the literature we found different ingrowth behaviours on using different
      biomaterials. Furthermore, we found a statistically significant influence of the
      immunological competence of the host with regard to ECM production. We draw the
      conclusion that immunological competence improves the ingrowth behaviour of
      biomaterials.

PMID- 15250012
TI  - [Size and shape of commercially available polyethylene particles for in-vitro and
      in-vivo-experiments].
AB  - AIM: The longevity of total hip arthroplasty is sometimes limited by osteolysis
      and aseptic loosening. Aseptic loosening may be caused by the biologic reaction
      to polyethylene wear particles. Particles of less than 1 micro m diameter are of
      particular importance. These particles are not easily available for experimental
      use. METHOD: We performed a morphologic analysis of commercially available, very
      small polyethylene particles (Ceridust(R)) in order to determine the specific
      size distribution. We measured 1 978 particles. Size analysis was performed using
      an electron microscope. Particle size was described as the equivalent circle
      diameter (ECD). Particle morphology was described as feret ratio. In addition,
      Ceridust(R) particles were compared to different particles stemming from a hip
      simulator experiment. RESULTS: More than 35 % of the particles were less than 1
      micro m in size. The particle size was 1.75 micro m +/- 1.43 micro m (median 1.42
      micro m). The minimum was 0.06 micro m, the maximum was 11.06 micro m. The feret
      ratio was 0.58 +/- 0.17 (median 0.63). The minimum was 0.07, the maximum was
      0.93. The majority of Ceridust(R) particles had a rough surface. Compared to
      polyethylene particles stemming from a hip simulator experiment, Ceridust(R)
      particles had a rougher surface, were less longitudinal, and had a more even size
      distribution. CONCLUSIONS: The pure, commercially available polyethylene
      particles analyzed here are suitable for in vitro and in vivo experiments due to
      their easy availability, minor costs, and large fraction of very small particles.

PMID- 15250013
TI  - Management of the febrile neutropenic patient: a consensus conference.

PMID- 15250014
TI  - Microbiological data for patients with febrile neutropenia.
AB  - The pattern of bacterial infections and antimicrobial susceptibility has changed
      significantly during the past 20-30 years. The causative organisms for bacteremia
      or fungemia identified at Kinki University Hospital in 1985-1996 were compared
      with the isolates identified during 1997-2002. The prevalence of gram-negative
      organisms decreased, whereas the prevalence of gram-positive organisms increased.
      Staphylococcal species predominated in the second period, accounting for 22% of
      isolates, and methicillin-resistant Staphylococcus aureus (MRSA) increased from
      5% to 14% of isolates. Pseudomonas aeruginosa ranked second, although the
      prevalence decreased in the second period compared with the first. Candida
      species were also relatively frequent (11%). Enterococcal species had an 8%
      prevalence. A comparison of all culture isolates showed that gram-negative
      isolates still predominated among the general patient population, whereas almost
      equal prevalence was observed in patients with hematological diseases. MRSA was
      the organism most frequently isolated in the general patient population, followed
      by P. aeruginosa. Among staphylococcal species, MRSA accounted for as much as 90%
      of isolates.

PMID- 15250015
TI  - Current antimicrobial usage for the management of infections in leukemic patients
      in Japan: results of a survey.
AB  - We report the findings of a questionnaire distributed by the Committee of
      Supportive Care of the Japan Adult Leukemia Study Group to 196 hospitals
      throughout Japan. For antimicrobial prophylaxis, the oral quinolones are
      prescribed by 38% of physicians and polymixin B by 31%. For antifungal
      prophylaxis, amphotericin B is prescribed by 42% of physicians and fluconazole by
      41%. Febrile neutropenia is empirically treated with cephalosporin or carbapenem
      monotherapy by 35% of physicians. Overall, dual therapy (i.e., an aminoglycoside
      plus a cephalosporin, a carbapenem, or an antipseudomonal penicillin) is
      prescribed by 50% of physicians. When response to initial empirical therapy does
      not occur after 3-4 days, 51% of physicians add an antifungal agent; fluconazole
      is preferred to amphotericin B (prescribed by 66% vs. 28% of physicians). For the
      treatment of fungemia due to Candida albicans, fluconazole was prescribed by 59%
      of physicians in cases of stable disease and amphotericin B was prescribed by 57%
      of physicians in cases of unstable disease. Amphotericin B is selected to treat
      invasive aspergillosis, but a dose of 0.5-0.7 mg/kg, inadequate for this disease,
      is prescribed by 44% of physicians. Granulocyte colony-stimulating factor is
      prescribed to treat patients with acute myelogenous leukemia who have life
      threatening infections (27% of physicians) or who have clinically or
      microbiologically documented infections (26% of physicians).

PMID- 15250016
TI  - Randomized trial of cefepime monotherapy or cefepime in combination with amikacin
      as empirical therapy for febrile neutropenia.
AB  - A multicenter open randomized trial was conducted to compare cefepime monotherapy
      with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic
      patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had
      microbiologically and 10.6% had clinically documented infections. Excellent
      response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients,
      respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of
      <500/ mu L receiving dual therapy had a better response than did those receiving
      monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with
      leukemia. Adverse events were minimal, and early death was observed in 7 patients
      in the dual therapy group and 5 patients in the monotherapy group. Overall,
      cefepime monotherapy is as effective as dual therapy for the initial treatment of
      febrile neutropenic patients. Further study is warranted for patients with severe
      neutropenia and leukemia who may benefit from dual therapy.

PMID- 15250017
TI  - Changes in the etiology of bacteremia in febrile neutropenic patients and the
      susceptibilities of the currently isolated pathogens.
AB  - The etiology of bacteremia in febrile neutropenic patients in the past few
      decades has shifted from gram-negative to gram-positive organisms. Potential
      reasons include the use of indwelling catheters, local environmental conditions,
      and the administration of specific antibiotic agents, especially as prophylaxis.
      Other factors may emerge from new studies, such as the categorization of febrile
      neutropenic patients into groups at low risk and at high risk of developing
      serious complications, continuing changes in resistance in the community, the use
      of antibiotic-coated catheters, and future changes in cytotoxic chemotherapy or
      antineoplastic therapy. In addition, there has been a drift in susceptibility
      patterns, with resistance issues seen in the general population of hospitalized
      patients now emerging in febrile neutropenic patients, as well as some issues
      specific to these patients. These changes affect empirical therapy as it was
      practiced a decade ago. Among the most commonly used agents, cefepime and
      carbapenems continue to show the highest rates of in vitro susceptibility,
      providing coverage against most gram-positive and gram-negative organisms and
      reducing the need for glycopeptides. Older agents continue to show degradation of
      their effectiveness. Among Pseudomonas aeruginosa strains, susceptibility to all
      agents continues to decline.

PMID- 15250018
TI  - Management of fever in neutropenic patients with different risks of
      complications.
AB  - Risk stratification of febrile neutropenic patients can have important
      implications in terms of management. The first prospectively validated risk
      scoring system was developed in 1992. A subsequent scoring system was developed
      in 2000, in which a score of < or =21 predicts a <5% risk for severe
      complications. Oral combination therapy in an ambulatory or home care setting is
      acceptable for low-risk patients. Hospital admission is mandatory for high-risk
      patients. Intravenous monotherapy can be given if neutropenia is anticipated to
      be of short duration; it is also acceptable if neutropenia is expected to be more
      prolonged but the patients is stable and do not have an infectious focus. All
      other patients should receive combination therapy with an aminoglycoside, if
      infection with a gram-negative pathogen is suspected, or a glycopeptide, if a
      gram-positive organism is suspected. However, antimicrobial therapy with coverage
      against gram-negative organisms should always be provided because of the
      significant mortality associated with these infections.

PMID- 15250019
TI  - Empirical antifungal therapy in treating febrile neutropenic patients.
AB  - Persistent or recurrent unexplained fever in neutropenic patients receiving
      antibiotics can be caused by invasive fungal infections, which are often
      difficult to diagnose. Early trials of empirical antifungal therapy with
      amphotericin B deoxycholate (AmB) documented reductions in the frequency of and
      the morbidity and mortality associated with invasive fungal infections. Because
      of AmB's infusional and renal toxicities, subsequent trials used newer, less
      toxic agents, such as the lipid formulations of AmB, the extended-spectrum
      azoles, and, more recently, the echinocandins. To date, alternatives to AmB have
      shown less toxicity, but improved efficacy has been less clear. Overall,
      empirical antifungal therapy can help prevent the morbidity associated with many
      fungal infections, eliminate concerns about diagnostic pitfalls, and prevent
      breakthrough undetected infections. However, its potential shortcomings are
      overtreatment, toxicity, and increased treatment-related costs when treatment is
      given to persons not needing it. Newer diagnostic tools are needed to target
      those most in need of antifungal therapy.

PMID- 15250020
TI  - The Infectious Diseases Society of America 2002 guidelines for the use of
      antimicrobial agents in patients with cancer and neutropenia: salient features
      and comments.
AB  - Infection remains the most common complication of chemotherapy-induced
      neutropenia. Bacterial infections predominate initially. Invasive fungal
      infections occur in patients with prolonged neutropenia. Chemoprophylaxis is
      recommended only for patients at high risk. Initial empirical therapy is based on
      local epidemiology and drug-susceptibility patterns. Patients at low risk can be
      treated as outpatients. Other patients need hospital-based, parenteral therapy.
      Several options are available, including combination regimens or monotherapy.
      Initial antimicrobial coverage against Pseudomonas species is necessary.
      Subsequent management depends on the nature of the febrile episode. If
      defervescence occurs within 3-5 days and no pathogen has been identified, the
      initial regimen or a suitable oral regimen can be used to complete a 7- to 10-day
      course. If the etiology has been established, therapy can be adjusted for optimal
      coverage (activity against gram-negative organisms must be maintained). If fever
      persists for longer than 3-5 days, assessment for a fungal infection, a resistant
      organism, or a new infectious focus should be conducted and empirical antifungal
      therapy instituted.

PMID- 15250021
TI  - Evidence-based recommendations for antimicrobial use in febrile neutropenia in
      Japan: executive summary.

PMID- 15250022
TI  - Clinical features of the neutropenic host: definitions and initial evaluation.
AB  - Initial evaluation of patients with febrile neutropenia includes a thorough
      history and physical examination; a complete blood cell count; measurement of
      serum creatinine, blood urea nitrogen, transaminases, and C-reactive protein; and
      culture of blood (samples from a peripheral vein and/or catheter). Chest
      radiography is indicated for patients with respiratory signs or symptoms. Signs
      and symptoms of inflammation may be minimal or absent. However, a search should
      be undertaken in the sites most commonly infected, including the periodontium,
      pharynx, lower esophagus, lung, perineum, eyes, and skin. Blood samples,
      including samples from catheter lumen(s), if present, and a peripheral vein,
      should be obtained for cultures for bacteria and fungi. Urine culture is
      indicated in the presence of signs or symptoms of urinary tract infection, a
      urinary catheter in place, or abnormal results of urinalysis. Fever is defined as
      a single axillary temperature measurement of > or =37.5 degrees C (oral
      temperature of > or =38.0 degrees C). Neutropenia is defined as a neutrophil
      count of <1000 cells/mm3.

PMID- 15250023
TI  - Monotherapy versus dual therapy based on risk categorization of febrile
      neutropenic patients.
AB  - Cefepime monotherapy was compared with cefepime-plus-amikacin dual therapy for
      treatment of febrile neutropenic patients. Response rates were significantly
      lower for patients receiving monotherapy who had neutrophil counts of <500
      cells/mm3 but did not differ significantly between patients receiving dual
      therapy who had neutrophil counts of > or =500 cells/mm3 or <500 cells/mm3. Dual
      therapy is recommended for the initial treatment of patients with neutropenia
      with <500 cells/mm3. Dual therapy was significantly more effective in patients
      with neutropenia lasting <5 days. The response rates to monotherapy or dual
      therapy did not differ significantly when neutropenia persisted for > or =6 days,
      indicating that sustained neutropenia is a risk factor for failure of initial
      empirical therapy. The rate of response to monotherapy was lower in leukemic
      patients, whereas the rate of response to dual therapy did not differ between
      leukemic and nonleukemic groups. The rate of response to either monotherapy or
      dual therapy did not differ for patients with temperatures of > or =38 degrees C
      or 37.5 degrees C-38 degrees C. Overall, defervescence occurred in >80% of
      patients with mild infections, whereas only 32% of those with moderate to severe
      infection responded by day 3 and 69.8% by day 7.

PMID- 15250024
TI  - Initial empirical antimicrobial therapy: duration and subsequent modifications.
AB  - Neutropenic patients at low risk of complications can receive oral ciprofloxacin
      or levofloxacin as outpatients. These agents plus amoxicillin/clavulanate or
      other penicillins, cephalosporins, or penem compounds are indicated to treat
      infections with gram-positive organisms in patients with oral mucositis or skin
      lesions. Parenteral fourth-generation cephalosporins or carbapenems can be given.
      For high-risk patients, monotherapy with cefepime or the carbapenems can be used.
      Methicillin-resistant Staphylococcus aureus should be treated with vancomycin or
      teicoplanin. For combination therapy, a third- or fourth-generation cephalosporin
      or carbapenem plus an aminoglycoside is desirable. Defervescence in 3-5 days for
      at least 7 days is suggested for subsequent management. Initial antibiotic(s) can
      be continued for patients who remain in good condition. For persistent fever
      after 3-5 days, the patient should be thoroughly reassessed. An aminoglycoside
      should be added for those initially treated with monotherapy. The initial
      cephalosporin can be changed to another cephalosporin or a carbapenem, or the
      initial carbapenem can be changed to a broad-spectrum cephalosporin. For patients
      initially receiving dual therapy, the cephalosporin or carbapenem can be changed
      as with monotherapy, whereas the initial aminoglycoside should be changed to
      another aminoglycoside or intravenous ciprofloxacin.

PMID- 15250025
TI  - Antimicrobial prophylaxis in febrile neutropenia.
AB  - Antibiotics generally considered for antibacterial prophylaxis for
      immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones.
      Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly
      effective in preventing pneumonia due to Pneumocystis carinii. However, it can
      cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and
      development of bacterial resistance, and it lacks activity against Pseudomonas
      aeruginosa. Quinolones can reduce the occurrence of fever and infections in
      patients with neutropenia but do not provide adequate coverage against gram
      positive bacteria, and inappropriate use can induce resistance among gram
      negative organisms. Routine antibacterial prophylaxis is not recommended for
      patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in
      settings in which fungal infections are frequent. Fluconazole is recommended for
      patients who are to undergo hematopoietic stem cell transplantation; it can be
      considered for elderly patients with acute leukemia who are to receive intensive
      chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is
      generally not indicated; however, it should be given to hematopoietic stem cell
      transplant recipients.

PMID- 15250026
TI  - Economic issues: toward a cost-effective approach to the management of febrile
      neutropenia in Japan.
AB  - The cost of treating neutropenic patients unexplained fever is of significant
      concern in Japan because of the depressed economy and the aging population.
      Development of a standardized treatment methodology specifically tailored to the
      situation in Japan will make the treatment more efficient for health care
      institutions, will allow for improved monitoring of practices and costs, and will
      result in better patient care. It is essential, however, that the welfare of the
      patients be the utmost priority--cost savings is not sufficient in the absence of
      a significant impact on morbidity and mortality.

PMID- 15250027
TI  - Estimating the rate of gene conversion on human chromosome 21.
AB  - There is a growing recognition that gene conversion can be an important factor in
      shaping fine-scale patterns of linkage disequilibrium in the human genome. We
      devised simple multilocus summary statistics for estimating gene-conversion rates
      from genomewide polymorphism data sets. In addition to being computationally
      feasible for very large data sets, these summaries were designed to yield robust
      estimates of gene-conversion rates in the presence of variation in crossing-over
      rates. Using our summaries, we analyzed 21,840 biallelic single-nucleotide
      polymorphisms (SNPs) on human chromosome 21. Our results indicate that models
      including both crossing over and gene conversion fit the overall short-range data
      (0-5 kb) of chromosome 21 much better than do models including crossing over
      alone. The estimated ratio of gene-conversion rate to crossing-over rate has a
      range of 1.6-9.4, depending on the assumed conversion tract length (in the range
      of 500-50 bp). Removal of the 5,696 SNPs that occur in known mutational hotspots
      (CpG sites) did not significantly change our conclusions, suggesting that
      recurrent mutations alone cannot explain our data.

PMID- 15250029
TI  - Diabetes mellitus and alcohol.
AB  - Alcohol influences glucose metabolism in several ways in diabetic patients as
      well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and
      glycogenolysis, its acute intake without food may provoke hypoglycaemia,
      especially in cases of depleted glycogen stores and in combination with
      sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred
      fuel, which may initially lead to somewhat higher blood glucose levels and hence
      an insulin response in type 2 diabetic patients. Depending on the nature of the
      carbohydrates in the meal, this may be followed by reactive hypoglycaemia.
      Moderate consumption of alcohol is associated with a reduced risk of
      atherosclerotic disorders. Diabetic patients benefit from this favourable effect
      as much as non-diabetic patients. Apart from effects on lipid metabolism,
      haemostatic balance and blood pressure, alcohol improves insulin sensitivity.
      This improvement of insulin sensitivity may also be responsible for the lower
      incidence of type 2 diabetes mellitus reported to be associated with light-to
      moderate drinking. In case of moderate and sensible use, risks of disturbances in
      glycaemic control, weight and blood pressure are limited. Excessive intake of
      alcohol, however, may not only cause loss of metabolic control, but also
      annihilate the favourable effects on the cardiovascular system.

PMID- 15250030
TI  - Stroke in patients with diabetes mellitus.
AB  - The article's objective is to review the key advances in the scientific
      literature related to the association of stroke with diabetes mellitus and to
      summarize the current approaches to stroke prevention in diabetic patients. The
      key findings from the literature regarding stroke incidence in patients with
      diabetes, specific and nonspecific risk factors of stroke in the diabetic
      population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes
      duration, diabetic complications, insulin resistance/hyperinsulinemia, course and
      outcome of stroke in subjects with diabetes and/or hyperglycemia, and the
      peculiarities of type, site and size of stroke in diabetic patients are
      discussed. The results of recent clinical trials aimed at correcting
      hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with
      diabetes, are reviewed. The medical database Medline along with original articles
      from peer-reviewed journals were used for analysis. There is convincing evidence
      suggesting that diabetes mellitus represents a strong independent risk factor of
      stroke. The contribution of hyperglycemia to increased stroke risk is not proven.
      Data suggest an association of the full cluster of the insulin resistance
      syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while
      its association with hemorrhagic stroke remains controversial. Hyperglycemia is
      common in stroke patients, but it is not known whether it independently
      influences the course and outcome of stroke or merely reflects stroke severity
      and location. Aggressive control of arterial hypertension and dyslipidemia allows
      to decrease the risk of stroke in diabetic patients substantially, while the
      importance of glucose control for stroke prevention remains unproven.

PMID- 15250031
TI  - The kallikrein-kinin system, angiotensin converting enzyme inhibitors and insulin
      sensitivity.
AB  - The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large
      scale, in arterial hypertension has showed that these molecules can exert
      beneficial effects on insulin sensitivity and may reduce the occurrence of type 2
      diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may
      relate to their capacity to interfere with bradykinin (BK) metabolism and action.
      BK may participate in the regulation of substrate utilization by several tissues
      by improving blood flow and substrate delivery to the tissues and also by
      promoting translocation of glucose transporters. Moreover, BK has been shown to
      increase phosphorylation of insulin receptor and its cell substrates. BK also
      appears to improve the release of insulin. Furthermore, insulin may activate the
      kallikrein-kinin system, which consequently may increase its metabolic effects.
      However, in experimental diabetes mellitus, BK can participate to the
      inflammatory reaction leading to Langerhans islets destruction. In diabetes,
      whereas tissue kallikrein mRNA levels were reduced in several organs, an
      overexpression of kinin receptors, an increase in plasma levels of kininogens and
      kallikrein and an activation of the kinin system have all been reported. Lastly,
      kinins may be involved in the development of diabetic nephropathy. Reduction of
      kinin metabolism by ACE inhibitors might be involved in the beneficial effects
      exerted by these compounds in diabetic kidney functions.

PMID- 15250032
TI  - LDL oxidative modifications in well- or moderately controlled type 2 diabetes.
AB  - BACKGROUND: The aim of the study was to examine, by measurement of specific
      indicators of free radical-mediated oxidation of LDL, whether there is evidence
      of increased in vivo oxidation of LDL in type 2 diabetic patients, and to
      investigate their associations with carotid intima media thickness (IMT).
      METHODS: In native LDL, we quantified five different products of LDL oxidation
      reflecting various stages of LDL oxidative modification in 38 individuals with
      well- or moderately controlled type 2 diabetes (HbA(1c) </= 8.5%) and 38 gender
      matched subjects with normal glucose metabolism. Baseline conjugated dienes
      (BCD), 7-OH-glycero-phosphocholine (7-OH-GPC), lyso-phosphatidylcholine (lyso
      PC), and ketocholesterol were determined in LDL, and circulating in vivo oxidized
      apolipoprotein B100 (Ox-apoB) was measured in plasma. The IMT of the carotid
      artery was measured by ultrasound. RESULTS: Borderline higher carotid IMT values
      were observed in individuals with diabetes (0.88 +/- 0.14 vs 0.83 +/- 0.11 mm, p
      = 0.06). LDL-ketocholesterol (45.5 +/- 19.4 vs 37.1 +/- 13.8 nmol/mmol LDL
      cholesterol, p < 0.05) and Ox-apoB (25.3 +/- 5.5 vs 22.2 +/- 5.8 U/mmol LDL
      cholesterol, p < 0.05) were significantly increased in diabetic patients. The
      concentration of BCD, 7-OH-GPC and lyso-PC in LDL did not differ between diabetic
      patients and control subjects. No significant correlations were demonstrated
      between the measured indicators of LDL oxidation and carotid IMT. CONCLUSION:
      Levels of BCD, 7-OH-GPC and lyso-PC, that is, intermediary products of LDL
      oxidation, were not significantly elevated, but ketocholesterol and Ox-apoB, that
      is, stable end products of the oxidation process, were increased in diabetic
      patients. We conclude that in vivo oxidation of LDL is increased, even in
      subjects with well- or moderately controlled type 2 diabetes.

PMID- 15250033
TI  - Peroxidase activity in the intestinal tract of Wistar-Furth, BBc and BBdp rats.
AB  - BACKGROUND: The development of immune-mediated diabetes in BB rats may involve an
      inflammatory lesion of the intestinal tract. METHODS: In order to further explore
      this issue, the activity of peroxidase was measured, in the absence and presence
      of either bromide or dapsone, at day 10, 30, 45, 70, 95 and 120 in three segments
      (top, mid and bottom) of the intestinal tract from Wistar-Furth rats and both
      diabetes-resistant and diabetes-prone BB rats fed after weaning either diabetes
      promoting diets or a protective diet, which decreases the incidence of diabetes
      in the BB rats. RESULTS: In the present study, from day 30 onwards, an age
      related increase in peroxidase activity was found in the intestine of diabetes
      prone BB rats (BBdp rats) fed diabetogenic diets, when compared with either
      Wistar-Furth or diabetes-resistant BB rats (BBc rats). This increase was most
      pronounced in the distal segments of the intestinal tract. Even when fed a
      protective diet, higher peroxidase activity was found in BBdp than BBc rats. Yet,
      in BBc rats, and to a lesser extent in BBdp rats, the diabetogenic diets lowered
      peroxidase activity below the value found in rats of the same strain fed the
      protective diet. There was a tight correlation between the activity of peroxidase
      and its susceptibility to be increased by bromide. CONCLUSION: It is proposed
      that diabetogenic diets may decrease peroxidase activity in intestinal cells,
      this effect becoming masked in BBdp rats by an age-related increase in the
      contribution of inflammatory cells. The latter phenomenon affects preferentially
      the distal segments of the intestinal tract.

PMID- 15250034
TI  - Decrease in mitochondrial oxidative protein damage parameters in the
      streptozotocin-diabetic rat.
AB  - BACKGROUND: Many authors have shown that hyperglycemia leads to an increase in
      oxidative protein damage in diabetes. The aim of this study was to reveal the
      susceptibility of mitochondria from liver, pancreas, kidney, and skeletal muscle
      of diabetic Sprague-Dawley rats, a model of type 1 diabetes, to oxidative protein
      damage. METHODS: Mitochondrial fractions were obtained by differential
      centrifugation. To show the effect of hyperglycemia in promoting oxidative
      protein damage, we determined mitochondrial protein carbonyl, total thiol,
      nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide
      levels. The levels of the studied markers, except nitrotyrosine, were determined
      by colorimetric methods. Nitrotyrosine levels were measured by ELISA. All values
      were compared with those of the controls by using the Mann-Whitney U-test.
      RESULTS: Nitrotyrosine and lipid hydroperoxide levels were decreased and other
      parameters were not changed in liver mitochondria of diabetic rats. Protein
      carbonyl, nitrotyrosine, advanced oxidation protein products, and lipid
      hydroperoxide levels were decreased and total thiol levels were not changed in
      pancreas mitochondria of diabetic rats. Only advanced oxidation protein products
      and lipid hydroperoxide levels were decreased in kidney mitochondria of diabetic
      rats. The levels of the same parameters were not significantly different in
      muscle mitochondria of diabetic rats. CONCLUSIONS: The decrease in mitochondrial
      oxidative protein damage in diabetes may correspond to either an increase in
      antioxidant defense mechanisms or a different adaptive response of the cells to
      the increased extramitochondrial oxidative stress in diabetes. The mitochondrial
      oxidative protein damage-lowering mechanisms in diabetes remain to be clarified.

PMID- 15250035
TI  - Genetic screening for individuals at high risk for type 1 diabetes in the general
      population using HLA Class II alleles as disease markers. A comparison between
      three European populations with variable rates of disease incidence.
AB  - BACKGROUND: To develop screening strategies for identification of individuals at
      increased genetic risk for type 1 diabetes in three populations with variable
      disease incidence rates and distinct ethnic origin. METHODS: A stepwise HLA DQB1
      DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset
      type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and
      Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece)
      or healthy schoolchildren (n = 177 from Hungary) served as controls. RESULTS: The
      DQB1*02/0302 genotype conferred the highest disease risk in all populations. The
      DQB1*02/y (y not equal DQB1*0301,*0302,*0602,*0603, *0604) genotypes were more
      common and conferred a higher disease risk in the Greek population (OR 4.9)
      compared to the Finns (OR 1.2). DQB1*0302/x (x not equal DQB1*02, *0301, *0602,
      *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases
      (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective
      DQB1*0602 or *0603 positive genotypes were most common in the Finns, while
      DQB1*0301 was more common in Hungarians and Greeks. In all groups, DQA1 and
      DRB1*04 typing considerably increased the sensitivity of the DQB1-based
      screening. The different high-risk genotype combinations present in about 10% of
      the background population had a diagnostic sensitivity of 60% in Finland and 80%
      in Hungary and Greece. CONCLUSIONS: HLA DR-DQ-based screening is a feasible tool
      for the identification of individuals at increased genetic risk for type 1
      diabetes in populations with diverse genetic background. The risk markers should,
      however, be individually selected for the target population since the screening
      efficiency of various markers is highly dependent on the ethnic group studied.

PMID- 15250037
TI  - Current literature in diabetes.

PMID- 15250036
TI  - Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and
      pericytes cultured in high glucose.
AB  - BACKGROUND: High glucose induces pathological alterations in small and large
      vessels, possibly through increased formation of AGE, activation of aldose
      reductase and protein kinase C, and increased flux through the hexosamine
      pathway. We showed previously that thiamine and benfotiamine correct delayed
      replication and increase lactate production in endothelial cells subjected to
      high glucose. We now aim at verifying the effects of thiamine and benfotiamine on
      cell cycle, apoptosis, and expression of adhesion molecules in endothelial cells
      and pericytes, under high ambient glucose. METHODS: Human umbilical vein
      endothelial cells and bovine retinal pericytes were cultured in normal (5.6
      mmol/L) or high (28 mmol/L) glucose, with or without thiamine or benfotiamine, 50
      or 100 micro mol/L. Apoptosis was determined by two separate ELISA methods,
      measuring DNA fragmentation and caspase-3 activity, respectively. Cell cycle and
      integrin subunits alpha3, alpha5, and beta1 concentration were measured by flow
      cytometry. RESULTS: Apoptosis was increased in high glucose after 3 days of
      culture, both in endothelium and pericytes. Thiamine and benfotiamine reversed
      such effects. Neither cell cycle traversal nor integrin concentrations were
      modified in these experimental conditions. CONCLUSIONS: Thiamine and benfotiamine
      correct increased apoptosis due to high glucose in cultured vascular cells.
      Further elucidations of the mechanisms through which they work could help set the
      basis for clinical use of this vitamin in the prevention and/or treatment of
      diabetic microangiopathy.

PMID- 15250038
TI  - Current trends in quantitative structure activity relationships on FXa
      inhibitors: evaluation and comparative analysis.
AB  - This article evaluates the quantitative structure activity relationships of FXa
      inhibitors, using the C-QSAR program of Biobyte. Diaryloxypyridines,
      aminophenols, biaryl isoxazoline derivatives, 1,2-dibenzamidobenzenes, 3
      amidinophenylalanine derivatives, benzoxazinones, naphthoanilides, tetrazoles,
      glucolic and mandelic acid derivatives were included in this survey. Clog P plays
      a significant role in the QSAR, especially as hydrophilicity. In the most of the
      cases, CMR/MR molar refractivity as well as sterimol parameters (B5 and L) are
      important. Electronic effects with the exception of the Hammett's constant
      sigmam, are not found to govern the biological activity. Es was found to be
      important indicator variables were used after the best model was found to account
      for the usual structural features.

PMID- 15250039
TI  - Challenges and strategies: the immune responses in gene therapy.
AB  - The host immune responses, including T lymphocytes mediated immune response and
      humoral immune responses are the important parts of the challenges in gene
      therapy. There are some potential immunostimulants in gene delivery systems, such
      as viral and non-viral vectors. Viral gene products, transgene products, viral
      proteins derived from viral particles required by dead-end infection, and CpG DNA
      in plasmid may play important roles in inducing the host immune responses when
      foreign genes are transferred into the targeted tissues. The immune responses
      should lead to many problems in gene therapy: transient expression of therapeutic
      gene, non-efficient re-administration of the same vectors, and severe side
      effects in clinical trials. Although RNAi may act as gene therapeutic agent for
      suppression of specific gene expression, little attention has been given to the
      potential non-specific effects that might be induced. It was reported that small
      interfering RNAs (siRNAs) can induce the host interferon response following
      transfected to mammalian cells. Facing these challenges, a number of studies have
      been focused on taking measures to solve them, such as immunosuppression,
      selection of different administration routes and dose of the vectors, using the
      tissue-specific promoters and modifying the vectors.

PMID- 15250040
TI  - Towards an understanding of organic anion transporters: structure-function
      relationships.
AB  - Organic anion transporters (OAT) play essential roles in the body disposition of
      clinically important anionic drugs, including anti-viral drugs, anti-tumor drugs,
      antibiotics, anti-hypertensives, and anti-inflammatories. The activities of OATs
      are directly linked to drug toxicity and drug-drug interactions. So far, four
      members of the OAT family have been identified: OAT1, OAT2, OAT3, and OAT4. These
      transporters share several common structural features including 12 transmembrane
      domains, multiple glycosylation sites localized in the first extracellular loop
      between transmembrane domains 1 and 2, and multiple phosphorylation sites present
      in the intracellular loop between transmembrane domains 6 and 7, and in the
      carboxyl terminus. The impact of these structural features on the function of
      these transporters has just begun to be explored. In the present review, the
      author will summarize recent progress made from her laboratory as well as from
      others, on the molecular characterization of the structure-function relationships
      of OATs, including particular amino acid residues/regions of the transporter
      protein ("molecular domains") that potentially determine transport
      characteristics.

PMID- 15250041
TI  - Cell processing: current status and future directions.
AB  - Specialized clinical cell processing began in the Department of Transfusion
      Medicine at the National Institutes of Health in 1984. The number and complexity
      of procedures performed increased quickly and in 1997 a highly specialized cell
      processing laboratory was opened. The laboratory has approximately 3,000 square
      feet, specialized air handing, a highly trained staff, and written laboratory
      procedures. In addition to standard laboratory equipment, the laboratory has
      numerous cell isolation instruments, flow cytometers, and automated cell counting
      instruments. The laboratory supports blood and bone marrow transplant protocols
      by isolating CD34+ stem cells, removing T lymphocytes, culturing lymphocytes to
      eliminate donor lymphocytes that are reactive with recipient alloantigens, and
      stimulating lymphocytes to induce Th2 type cells to reduce graft versus host
      disease. The laboratory has also been preparing dendritic cells to support
      protocols using immune therapy to treat cancer. In addition, pancreatic islet
      cells are isolated from organ donors for transplantation to treat type I diabetes
      mellitus.

PMID- 15250042
TI  - Government regulations on cellular therapy and proposed approach related with
      these products by KFDA.
AB  - Advances in biomedical technology has enabled the research and use of novel
      therapies in cellular transplantation. A number of trials using chondrocyte and
      autologous skin products are underway and will soon become commercially available
      for clinical utilization. However, the Korea Food and Drug Administration
      currently lack systematic regulations for efficacy and safety evaluation of the
      emerging therapies. Specifically, dose related studies are uncontrolled and
      availability of clinical research centers is inadequate. Thus, patients are
      receiving therapy without guidelines for indication, dose, and adequate safety
      profiles. We propose criteria for cases in which these therapies can be used and
      advocate IRB determined quality assurance for future research.

PMID- 15250043
TI  - The fetal sheep: a unique model system for assessing the full differentiative
      potential of human stem cells.
AB  - The naturally occurring stem cell migratory patterns, the availability of
      expanding homing and engraftment sites, and the presence of tissue/organ-specific
      signals in the developing mammalian fetus provide the ideal setting for stem
      cells to exhibit their full biological potential. These characteristics combined
      with the relative immunological naivete of the early gestational age fetus that
      permits the engraftment and long-term persistence of allogeneic and xenogeneic
      donor stem cells make it possible to use the developing fetus to assess the in
      vivo potential of a variety of stem cells. We have taken advantage of these
      permissive characteristics of the fetus to develop a large animal model of human
      hematopoiesis in sheep that permits not only the long-term engraftment of human
      hematopoietic stem cell/progenitor cells and their differentiation into the full
      range of lymphohematopoietic elements, but also the relatively robust expression
      of their potential to contribute to the formation of non-hematopoietic tissues.

PMID- 15250044
TI  - Mechanism of immune response during immunotherapy.
AB  - Tumor immunology embraces an extensive array of biological phenomena that include
      interactions between neoplastic cells and the innate and adaptive immune
      response. Among immune cells, T cells have taken the center stage because they
      can be easily demonstrated to specifically recognize autologous cancer cells.
      However, their role is limited and other components of the immune response are
      likely necessary for the completion of cancer rejection. Metastatic melanoma and
      renal cell carcinoma (RCC) are malignancies strongly predisposed to regress in
      response to the systemic administration of high-dose interleukin (IL)-2. Several
      clinical Studies in extensive cohorts of patients have shown that this treatment
      can induce complete or partial clinical regressions of metastatic disease in 15
      to 20% of patients who receive this treatment. Although IL-2 has direct pluri
      potent effects on cells with immune and inflammatory function, it remains
      unexplained which cell subset is implicated in mediating tumor regression. In a
      quest to characterize the mechanism of action of IL-2 during the course of
      immunotherapy, we have investigated the early changes in transcriptional profiles
      of circulating mononuclear cells and microenvironment of melanoma metastases
      following high dose IL-2 administration (720,000 IU/kg) by serial sampling of
      blood cells and tumors in the form of fine needle aspirate (FNA). Furthermore,
      studies are currently ongoing to characterize the proteomic profiling of RCC
      patients undergoing the same treatment using protein arrays (manuscript in
      preparation). The predominant activation of genes related to inflammation and
      activation of mononuclear phagocytes lead us to further characterize this cell
      subset in the context of stimulation with a panel of soluble factors potentially
      present in the circulation and tumor microenvironment.

PMID- 15250045
TI  - Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised
      patients.
AB  - Cytomegalovirus (CMV) reactivation in immune compromised patients such as those
      undergoing hematopoietic progenitor cell transplantation (HPCT) and those with
      HIV infections can cause severe morbidity and mortality despite treatment with
      appropriate antiviral agents. The recovery of Cytomegalovirus (CMV) specific
      cytotoxic T lymphocytes (CTL) plays an important role in the reconstitution of
      CMV specific immunity in immunocompromised patients. Recent studies have reported
      that CMV reactivation can be successfully treated by adoptive transfer of CMV
      specific T cell clones from CMV seropositive donors expanded in vitro with CMV
      infected fibroblasts or lysates of CMV infected cells. Other studies have used
      immune dominant CMV proteins or peptides to expand CMV-specific cytotoxic T
      lymphocytes. This review describes the clinical manifestations of CMV disease in
      immunocompromised patients, recent advances of antiviral therapy for CMV disease,
      the principals of the induction of cellular immune response to CMV, and the
      clinical application of CMV immunotherapy.

PMID- 15250046
TI  - Efficient induction of dopaminergic neurons from embryonic stem cells for
      application to Parkinson's disease.
AB  - For cell replacement therapy of neurodegenerative diseases such as Parkinson's
      disease (PD), methods for efficiently generating midbrain dopaminergic (DA)
      neurons from embryonic stem (ES) cells have been investigated. Two aspects of DA
      neuron generation are considered: genetic modification and manipulation of
      culture conditions. A transcription factor known as critical for development of
      DA neurons, Nurr1, was introduced into ES cells to see how they facilitate the
      generation of DA neurons from ES cells. Also, two culture procedures, the 5-stage
      method and stromal cell-derived inducing activity (SDIA) method, were used for ES
      cell differentiation. Using the 5-stage method, we and others previously
      demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling
      molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can
      differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+
      neurons). Furthermore, using the SDIA method with treatment of signaling
      molecules, we found that Nurr1-overexpressing ES cells can differentiate to DA
      neurons with the highest efficiency ever reported (approximately 90% of TH+/Tuj1+
      neurons). Importantly, our semi-quantitative and real-time PCR analyses
      demonstrate that all known DA marker genes (e.g., TH, AADC and DAT) were up
      regulated in Nurr1- overexpressing ES cells when compared to the na ve ES cells.
      These cells produced increased dopamine compared to na ve D3 cells after
      differentiation. In the in vivo context after transplantation, the genetically
      modified ES cells also showed the highly increased dopaminergic neuronal
      phenotypes. Thus, the combination of genetic engineering and appropriate culture
      conditions provides a useful tool to generate a good cell source from ES cells
      for cell replacement therapy of degenerative diseases such as PD.

PMID- 15250047
TI  - Gene therapy and cell transplantation for Alzheimer's disease and spinal cord
      injury.
AB  - The targeted delivery of genes and the transplantation of suitable cell types
      into the adult nervous system have received considerable interest over the last
      years. The development of improved vector systems for in vivo gene delivery and
      the discovery of neural stem cells in the adult nervous system have opened new
      venues for potential therapeutic intervention in progressive neurodegenerative
      disease and nervous system injury. Thus, strategies have evolved for the delivery
      of potentially neuroprotective molecules, such as neurotrophic factors, and the
      replacement of cells and tissue lost due to CNS injury and degeneration.

PMID- 15250048
TI  - Gene and cell replacement via neural stem cells.
AB  - Neural stem cells (NSCs) are operationally defined by their ability to self
      renew, to differentiate into cells of all glial and neuronal lineages throughout
      the neuraxis, and to populate developing or degenerating central nervous system
      (CNS) regions. Thus their use as graft material can be considered analogous to
      hematopoietic stem cell-mediated reconstitution and gene transfer. The
      recognition that NSCs propagated in culture could be reimplanted into mammalian
      brain, where they might integrate appropriately throughout the mammalian CNS and
      stably express foreign genes, has unveiled a new role for neural transplantation
      and gene therapy and a possible strategy for addressing the CNS manifestations of
      diseases that heretofore had been refractory to intervention. NSCs additionally
      have the appealing ability to home in on pathology, even over great distances.
      Such observations help to advance the idea that NSCs--as a prototype for stem
      cells from other solid organs--might aid in reconstructing the molecular and
      cellular milieu of maldeveloped or damaged CNS.

PMID- 15250049
TI  - Chondrogenic differentiation of mesenchymal stem cells and its clinical
      applications.
AB  - Tissue engineering has the potential to provide cartilaginous constructs capable
      of restoring the normal function of native articular cartilage following joint
      injury or degradation. One approach to functional tissue engineering of cartilage
      involves the in vitro cultivation of tissue constructs by using: (i) chondrogenic
      cells that can be selected, expanded, and transfected to overexpress the genes of
      interest, (ii) scaffolds that provide a defined three-dimensional structure for
      tissue development and biodegrade at a controlled rate. Understanding the
      functional potential of the cells and the signaling mechanisms underlying their
      differentiation should lead to innovative protocols for clinical orthopaedic
      interventions. A large number of growth factors and hormones have been implicated
      in the regulation of chondrocyte biology, relatively little is known about the
      intracellular signaling pathways involved. We have tried to define the roles of
      specific TGF- dependent signaling pathways involved in the regulation of
      chondrogenesis from human mesenchymal stem cells. Chondrogenesis induced by TGF
      beta3 in alginate bead system was confirmed by examining cartilage specific type
      II collagen expression and aggrecan, whereas type I collagen expression was not
      affected by TGF-beta3. Type II collagen mRNA expression was expressed strongly
      during chondrogenesis and MEK inhibition (U0126) resulted in complete down
      regulation of type II collagen. In contrast, aggrecan expression was detected in
      same level by treatment of U0126. These results strongly suggest that the ERK
      signaling cascade is involved in TGF-beta3 induced-chondrogenesis signaling
      pathways and a role of its pathway is necessary over a longer period to promote
      type II collagen expression. However, their end product properties in vivo have
      not been well known. In this study, an articular cartilage from chondrogenic MSCs
      with PLGA scaffolds (75:25 and 65:35) were made and analyzed its biochemical,
      histological and mechanical properties in vitro and in vivo. And also, we
      evaluated the cartilage formation in vivo through the injection of cell
      thermosensitive gel complex, a newly developed injectable material. At 12 weeks
      after PLGA scaffolds containing chondrogenic MSCs transplantation, the separated
      rabbit distal femur showed a good gross articular cartilage appearance in the
      transplanted site. In indentation test, compare to the native articular
      cartilage, the engineered cartilage from two types of (75:25 and 65:35) achieved
      up to 30-60% in mechanical stiffness. And also, a new model for cartilage
      formation in bladder, at 14 weeks after injection, we could find out mass
      formation in the submucosal area grossly. H&E staining, alcian blue staining and
      other special staining confirmed the chondrogenic differentiation in the mass.
      These cell therapy technologies can provide the possibility of clinical
      applications for vesicoureteral reflux and reflux esophagitis, and urinary
      incontinence as well as articular cartilage regeneration.

PMID- 15250050
TI  - Strategies to improve dendritic cell-based immunotherapy against cancer.
AB  - Dendritic cells (DCs) play a pivotal role in T cell-mediated immunity and have
      been shown to induce strong antitumor immune responses in vitro and in vivo.
      Various approaches utilizing different vaccine cell formats, cell numbers,
      vaccination schedule, site of vaccination and maturation stages of DCs were
      investigated worldwide. While clinical trials have demonstrated the safety of
      such strategies, the clinical outcome was less than expected in most cases. This
      is due to in part host immunodeficiency imposed by tumors and immunoediting of
      tumor cells. To overcome these obstacles, new approaches to improve DC-mediated
      immunotherapeutic strategies are under investigation. First, functional
      enhancement of monocyte-derived DCs can be generated with using flt3-ligand (FL).
      Second, diverse antigenic determinants from heat shock-treated tumor cells may
      improve the immunogenicity of DC-based vaccines. Third, inclusion of ex vivo
      expanded NK/NKT cells in DC-based vaccines could be beneficial since the
      bidirectional interaction of these two cell types are known to enhance NK cell
      effector function and to induce DC maturation. Application of these approaches
      may induce a broadened antitumor immune response and thereby promote the
      elimination of tumor antigen-negative variant clones that had escaped
      immunosurveillance or undergone immunoediting. We are currently examining the
      feasibility of these immunotherapeutic approaches using a murine pancreatic
      cancer model system.

PMID- 15250051
TI  - Islet transplantation and regeneration for treatment of diabetes.
AB  - Islet transplantation has the potential to restore normoglycemia and prevent the
      development of diabetic complications such as retinopathy, nephropathy and
      neuropathy, and could therefore ve a valuable treatment for diabetic patients.
      The scarcity of available islets is an obstacle for clinically successful islet
      transplantation. To resolve the problems, we have examined the two methods, islet
      transplantation with extracellular matrix and in vivo expansion of islets with
      electrically-transfection of growth factors.

PMID- 15250052
TI  - Caged pancreatic islet for IDDM.
AB  - The goals of this research are to improve the functionality (insulin secretion
      rate and pattern) and to expand the life-span of immunoprotected pancreatic
      islets. The low functionality (less than 15% of the insulin release rate of
      native islets in pancreas) required a large number of islets within the implant,
      which causes complications in surgery and discomfort for patients. The limited
      life-span of the islets in a biohybrid artificial pancreas (BAP) may require
      frequent cell reseeding and cause further supply problems in islet
      transplantation. Improved islet functionality and prolonged life-span will
      minimize the volume of the BAP by reducing the number of islets needed for
      diabetic patients to achieve normoglycaemia and reduce problems associated with
      islet supply. It is hypothesized in this research that 1) by mimicking
      facilitated oxygen transport in avascular tissues, the immunoprotected islets
      release a higher amount of insulin, recover their intrinsic biphasic release
      pattern, and prolong their life-span, and 2) insulinotropic agents further
      promote insulin secretion from islets. Based on these hypotheses, a new BAP
      system will be designed which contains the water-soluble polymeric conjugates of
      oxygen carriers (or oxygen binding vehicles) and islet stimulants of sulfonylurea
      compounds and glucagon-like insulinotropic peptide-1 with entrapped islets in the
      BAP. The research examines their effects on islet viability, the amount of
      insulin secretion, the insulin release profile, and the life-span of
      immunoprotected pancreatic islets. Especially, the combined synergy effects of
      both hypotheses will be emphasized. The successful results in improving
      functionality and life-span of islets entrapped in an immunoprotected membrane
      can be applied in the delivery of microencapsulated therapeutic cells and to the
      miniaturization of a BAP. In addition, the approaches proposed in this research
      will provide a potential solution to the shortage problem of human cell or tissue
      sources.

PMID- 15250053
TI  - Clinical application of marrow mesenchymal stem cells for hard tissue repair.
AB  - Human marrow mesenchymal stem cells were cultured in a medium containing
      glycerophosphate, ascorbic acid, and dexamethasone (Dex) on alumina ceramic discs
      and on tissue culture polystyrene (TCPS) dishes. Cell proliferation followed by
      osteogenic differentiation was observed to be equal on both culture substrata.
      The differentiation resulted in the appearance of bone-forming osteoblasts, which
      fabricated mineralized matrices on these substrata. Stem cells kept at 4 degrees
      C for 24 h outside a CO2 incubator maintained a viability level of more than 90%.
      The regenerative cultured bone outside the incubator also maintained high
      alkaline phosphatase activity for several hours. These results verified that
      cultured bone fabricated at a cell processing center can be transported to
      distant hospitals for use in hard tissue repair. To date, the tissue engineered
      cultured bone formed on alumina ceramics in this environment have already been
      used in clinical situations, such as total ceramic ankle replacements.

PMID- 15250054
TI  - Biologic therapy for brain cancers--based on cellular and immunobiology.
AB  - The overall goal of our research projects is to develop effective
      immunotherapeutic regimens, particularly combining vaccine and gene therapy/ cell
      therapy strategies. For the development of clinically effective immunotherapy for
      brain cancers, the following issues are considered to be particularly important:
      1) Induction of effective immune responses against tumors (afferent arm of the
      immune response), 2) Delivery of immune effector cells to the target tumor sites
      and maintaining the activity of the effector cells (efferent arm), 3) For
      specific and safe immunotherapy, specific brain tumor rejection antigens have to
      be identified, 4) Feasibility, safety and efficacy need to be tested in a series
      of clinical trials. The following presentation summarizes my research projects
      and demonstrates how each plan will fit in the whole schema of designing
      successful immunotherapeutic strategies for brain cancers. In this presentation,
      I would like to focus on our clinical and basic studies related to the vaccine
      strategies for patients with glioma, and modulation of tumor-microenvironment
      using bone-marrow derived stroma cells as vehicles for cytokine- gene delivery.

PMID- 15250062
TI  - Cinacalcet for secondary hyperparathyroidism in hemodialysis recipients.

PMID- 15250063
TI  - Ten years of alendronate treatment for osteoporosis in postmenopausal women.

PMID- 15250064
TI  - Ten years of alendronate treatment for osteoporosis in postmenopausal women.

PMID- 15250065
TI  - Ten years of alendronate treatment for osteoporosis in postmenopausal women.

PMID- 15250066
TI  - Infections associated with surgical implants.

PMID- 15250067
TI  - Infections associated with surgical implants.

PMID- 15250068
TI  - Infections associated with surgical implants.

PMID- 15250069
TI  - Support for the RV144 HIV vaccine trial.

PMID- 15250070
TI  - Exact reconstruction in 2D dynamic CT: compensation of time-dependent affine
      deformations.
AB  - This work is dedicated to the reduction of reconstruction artefacts due to motion
      occurring during the acquisition of computerized tomographic projections. This
      problem has to be solved when imaging moving organs such as the lungs or the
      heart. The proposed method belongs to the class of motion compensation
      algorithms, where the model of motion is included in the reconstruction formula.
      We address two fundamental questions. First what conditions on the deformation
      are required for the reconstruction of the object from projections acquired
      sequentially during the deformation, and second how do we reconstruct the object
      from those projections. Here we answer these questions in the particular case of
      2D general time-dependent affine deformations, assuming the motion parameters are
      known. We treat the problem of admissibility conditions on the deformation in the
      parallel-beam and fan-beam cases. Then we propose exact reconstruction methods
      based on rebinning or sequential FBP formulae for each of these geometries and
      present reconstructed images obtained with the fan-beam algorithm on simulated
      data.

PMID- 15250071
TI  - Reuse of a set for total intravenous anaesthesia: safe against bacterial
      contamination?

PMID- 15250072
TI  - [Primary coronary angioplasty for myocardial infarction in elderly patients].

PMID- 15250073
TI  - [Misdiagnosed primary hyperparathyroidism with generalized calcification of the
      organs].

PMID- 15250074
TI  - [Papillary fibroelastoma of the mitral valve].

PMID- 15250075
TI  - [Surgical "epidemiology" of commissures formation in the abdominal cavity].

PMID- 15250076
TI  - [Surgical approach in the treatment of focal liver diseases].

PMID- 15250077
TI  - [Problems and perspectives of endovideosurgical procedures in nodular lesions of
      the thyroid gland].

PMID- 15250078
TI  - [Endoscopic hemostasis in patients with bleeding peptic ulcer].

PMID- 15250079
TI  - [Misdiagnosis of a case of Hodgkin's disease as cervical vertebral tuberculosis
      and scabies].

PMID- 15250080
TI  - [Considerations about construction and administration of clinical key
      discipline].

PMID- 15250081
TI  - U.S. panel about to weigh in on rules for assisted fertility.

PMID- 15250082
TI  - [Alveolar soft-tissue sarcoma: report of one case].

PMID- 15250083
TI  - Harm to fetuses becomes issue in Utah and elsewhere.

PMID- 15250084
TI  - U.C.L.A. official is held in cadaver-selling inquiry.

PMID- 15250085
TI  - [Ultrasound-guided intraluminal thrombin injection for false aneurysm: report of
      one case].

PMID- 15250086
TI  - In science's name, lucrative trade in body parts.

PMID- 15250087
TI  - U.C.L.A. halts donations of cadavers for research: inquiry begins on selling of
      bodies and parts.

PMID- 15250088
TI  - Unlikely way to cut hospital costs: comfort the dying. Palliative-care unit
      offers painkillers and support; fewer tests, treatments.

PMID- 15250089
TI  - Ballot drive puts stem-cell funding in voters' hands. In California, diabetes
      groups show growing influence as they push for research; big backing from
      Hollywood.

PMID- 15250090
TI  - Making life's end a 'good death'.

PMID- 15250091
TI  - Designing a better place to die. Long focused on sustaining life at all costs,
      some ICUs add hospice-like services.

PMID- 15250092
TI  - Greater regulation of fertility encouraged. Bioethics Council seeking changes.

PMID- 15250093
TI  - An experiment in saving lives: emergency patients unwittingly get artificial
      blood.

PMID- 15250094
TI  - A myth worth keeping.

PMID- 15250096
TI  - Calibration verification and CAP.

PMID- 15250095
TI  - ["Anti-aging" from a cardiologist's view].
AB  - The bases of "anti-aging" therapy are smoking cessation, diet and physical
      activity. In addition, individuals can be identified, on the basis of their
      global vascular risk, who will benefit from pharmacotherapy to control blood
      pressure, lipids and platelet aggregation. From the cardiologist's perspective,
      there is at present no evidence indicating the use of vitamins, antioxidants or
      hormone therapy in cardiovascular prevention.

PMID- 15250097
TI  - [From the French Society of Plastic and Reconstructive Surgery to the French
      Society of Plastic Reconstructive and Aesthetic Surgery].
AB  - (The) 3rd December 1952, 11 surgeons and other specialists found the French
      Society of Plastic and Reconstructive Surgery (SFCPR) which was officially
      published on (the) 28 September 1953. The first congress was during October 1953
      and the first president as Maurice Aubry. The first secretary was Daniel Morel
      Fatio. The symposiums were after about three of four times each year and the
      thematic subjects were initially according the reconstructive surgery. The review
      "Annales de chirurgie plastique" was free in 1956. The members of the Society
      were about 30 initially, but their plastic surgery in the big hospitals at Paris
      and other big towns in France. The "specialty" of plastic surgery was created in
      1971. On "syndicate", one French board of plastic reconstructive and aesthetic
      surgery, the increasing of departments of plastic surgery were the front of
      increasing of the plastic surgery in French and of the number of the French
      Society of Plastic Reconstructive surgery (580 in 2003). The French Society
      organized the International Congress of Plastic Surgery in 1975. The society
      SFCPR became the French Society of plastic reconstruction and Aesthetic Surgery
      (SFCPRE) in 1983 and the "logo" (front view) was in the 1994 SOF.CPRE.

PMID- 15250098
TI  - [Radiological diagnosis of mammary carcinomas. I: pathology and x-ray
      mammography].
AB  - Breast cancer is the most common malignant tumor in women: almost 10 % will
      suffer from breast cancer during their life and almost half of these will die of
      it. The spectrum of radiologic methods for diagnosing breast cancer is wide,
      including X-ray mammography, ultrasound, magnetic resonance mammography, and
      minimally invasive biopsies. After long-lasting controversies, breast cancer
      screening using X-ray mammography has now been introduced in Germany, following
      the projects in the Netherlands and Sweden. However, assessing mammographic films
      under screening conditions requires skills distinctly different from those needed
      under clinical conditions. This first part of two covers the histopathological
      basics and X-ray mammography; the second will deal with ultrasound of the breast
      and magnetic resonance mammography.

PMID- 15250099
TI  - Tamm-Horsfall protein in patients with kidney damage and diabetes.
AB  - Tamm-Horsfall protein (THP) is a glycoprotein present abundantly in human urine.
      It is localized in the thick ascending limb of the loop of Henle (TAL) and the
      early distal convoluted tubule (DCT). The rate of urinary excretion of THP has
      been studied in various diabetic groups. It has been postulated that urinary THP
      may be a useful marker for renal damage. The aim of this study was to compare
      directly the immunogold localization of THP in diabetic and control kidney tissue
      specimens with or without kidney damage. Immunogold labeling was performed on
      archival tissue samples of 34 diabetic and 18 control human kidneys at the light
      microscope level. Slides were ranked as having a high, moderate or low degree of
      reaction. The majority of diabetic samples had a slightly lower degree of THP,
      while patients with known renal dysfunction had lowest THP. Previous studies have
      found a decreased excretion of urinary THP in diabetics. Our results show that
      decreased gold labeling is associated with known renal damage and may indicate
      damage to the thick ascending limb of the loop of Henle and the early distal
      convoluted tubule, irrespective of presence or absence of diabetes.

PMID- 15250100
TI  - Partial nephrectomy used to treat renal cell carcinoma arising in a live donor
      transplant kidney.
AB  - There are few reported cases of renal cell carcinoma (RCC) arising in kidney
      allografts. Whether these tumours occur due to post-transplant malignant
      transformation or are present at the time of transplantation is unclear. The
      influence of immunosuppression must be considered in their development,
      progression and treatment. We report a case of a RCC presenting asymptomatically
      in a functioning live donor renal allograft 173 months after transplantation. In
      an attempt to avoid return to dialysis treatment, a partial nephrectomy was
      carried out. To optimise the procedure, and to assure cancer clearance, combined
      intraoperative ultrasound and frozen section analysis were used. Our patient
      remains disease free and dialysis independent at 22 months follow up. To our
      knowledge, this patient represents the only live donor organ transplant tumour
      reported to be treated using nephron-sparing surgery and remain dialysis
      independent. Partial nephrectomy should be considered as a treatment option in
      such cases.

PMID- 15250101
TI  - The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced
      oxidative stress in rabbits.
AB  - Reactive oxygen species (ROS) can play an important role in the pathogenesis of
      ischemia-reperfusion (I/R) injury. Dehydroepiandrosterone (DHEA) is one of the
      hormones secreted from adrenal glands, and in some studies it has been shown that
      DHEA has antioxidant properties. This experimental study was designed to
      determine the effect of DHEA on I/R-induced oxidative stress in rabbit kidney.
      Twenty-one rabbits were divided into three groups. Rabbits were subjected to 60
      min of left renal pedicle occlusion followed by 24 h of reperfusion. DHEA (50
      mg/kg) (I/R + DHEA group) or equal volume of vehicle (I/R group) was administered
      3 h prior to ischemia. The control group received only laparotomy without I/R,
      DHEA or vehicle. At the end of the reperfusion periods, rabbits were decapitated.
      Renal tissues were taken for determination of malondialdehyde (MDA) levels as an
      indicator of lipid peroxidation and superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (GPX) activities as antioxidant enzymes. In the I/R
      group, while renal SOD and CAT activities were significantly lower, MDA levels
      were significantly higher than in the I/R + DHEA group and controls. In the I/R +
      DHEA group, enzyme activities and MDA levels were similar to the controls. There
      was no significant difference in terms of renal GPX activity among the groups.
      DHEA may have a beneficial effect on renal tissue against oxidative damage due to
      I/R by preventing decreases in some antioxidant enzyme activities.

PMID- 15250102
TI  - Expression of pro-angiogenic growth factors VEGF, EGF and bFGF and their
      topographical relation to neovascularisation in prostate cancer.
AB  - The aim of the study was to quantify the expression of vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF) and epidermal growth
      factor (EGF) in prostate cancer and adjacent non-tumorous tissue in a
      standardized experimental set-up and to evaluate the paracrine effects of three
      endothelial stimuli on neovascularisation. Immunohistochemical staining of
      prostate cancer (PCa) specimens for VEGF, bFGF, EGF and the endothelial marker
      CD31 was performed (n=56). Sections were analyzed for growth factor-positive
      cancer/epithelial cells as well as staining intensity in (I) malignant and (II)
      non-tumorous tissue. Within PCa the topographic relationship (TR) of maximum
      microvessel density (MWD) and maximum expression of each growth factor was
      assessed. The number of VEGF- and EGF-positive cells in PCa was significantly
      enhanced compared with non-tumorous tissue (p<0.0001), whereas there was no
      difference in staining intensity. In contrast, the staining intensity of bFGF
      sections revealed a stronger expression in non-tumorous tissue compared with PCa
      (p<0.0001). In benign glands, VEGF, EGF and bFGF expression is chiefly restricted
      to basal cells. VEGF and EGF displayed a close TR in 65 and 57% of cases,
      respectively, whereas bFGF revealed a close TR in only 43% of PCa specimens. The
      results outline the relationship of the investigated growth factors and
      angiogenesis in PCa, which is strongest for VEGF and EGF. The relevance of VEGF
      and EGF is underlined by the increased number of positive cancer cells. Although
      previously reported to be a pro-angiogenic growth hormone, bFGF appears to play
      an assimilably minor role in the angiogenesis of PCa.

PMID- 15250103
TI  - [Fifty years, forty-nine presidents].

PMID- 15250104
TI  - Assessment of availability of magnetic resonance angiography (MRA) in renal
      arteriovenous fistula.
AB  - We report two cases of cirsoid-type renal arteriovenous fistula (RAVF) which were
      difficult to differentiate from renal pelvic tumor by intravenous pyelogram (IVP)
      and computed tomography (CT) scan. Two women visited our department complaining
      of sudden asymptomatic macroscopic hematuria. CT scans showed an irregular mass
      in the right kidney. Magnetic resonance angiography (MRA) revealed a cirsoid-type
      RAVF. These patients were treated with transarterial embolization (TAE) using
      ethanol, geratin sponge, and a coil. It is suggested that MRA is useful for the
      diagnosis of renal arteriovenous fistula.

PMID- 15250105
TI  - [Family album].

PMID- 15250106
TI  - A clinical case illustrating the current diagnostic modalities for myocardial
      viability assessment.

PMID- 15250107
TI  - 'Back-to-the-future' connectivity.

PMID- 15250108
TI  - 2004: a lab odyssey.

PMID- 15250109
TI  - [Simple measurement of intrathyroid iodine kinetics].

PMID- 15250110
TI  - Report results; avoid risk.

PMID- 15250111
TI  - Accreditation and accountability.

PMID- 15250112
TI  - Human embryonic stem cell research: an intercultural perspective.
AB  - In 1998, researchers discovered that embryonic stem cells could be derived from
      early human embryos. This discovery has raised a series of ethical and public
      policy questions that are now being confronted by multiple international
      organizations, nations, cultures, and religious traditions. This essay surveys
      policies for human embryonic stem cell research in four regions of the world,
      reports on the recent debate at the United Nations about one type of such
      research, and reviews the positions that various religious traditions have
      adopted regarding this novel type of research. In several instances the religious
      traditions seem to have influenced the public-policy debates.

PMID- 15250113
TI  - Chinese researchers promote biomedical regulations: what are the motives of the
      biopolitical dawn in China and where are they heading?
AB  - In the past five years, China has experienced increased efforts to regulate
      activities in biomedical research and practice. Background is provided on some of
      the key developments in Chinese bioethics especially in relation to genetics,
      stem cells, cloning, and reproductive medicine. This background sets the stage
      for a document entitled "Ethical Guidelines for Human Embryonic Stem Cell
      Research," proposed by the Bioethics Committee of the Southern China National
      Human Gene Research Center, Shanghai, which is reprinted in this volume of the
      Kennedy Institute of Ethics Journal.

PMID- 15250114
TI  - Ethical guidelines for human embryonic stem cell research.

PMID- 15250115
TI  - [The many faces of endocarditis].
AB  - BACKGROUND: Over the past years we have had a relatively large number of patients
      in our hospital with endocarditis. There has been a variety of clinical
      presentations, as illustrated by the following case presentations. MATERIAL AND
      METHODS: We have conducted a search in our data-based archives of the period from
      1.1.1994 to 31.12.2001 and found 25 patients discharged with a diagnosis of
      endocarditis. We have chosen five case histories that we discuss in the context
      of published literature. RESULTS AND INTERPRETATION: The signs and symptoms
      presented include a stroke, severe back pain, a swollen knee, pneumonia and
      cardiac failure. We especially discuss intravenous drug users and endocarditis of
      the heart's right side.

PMID- 15250117
TI  - [Endocarditis problems].

PMID- 15250116
TI  - [A 34-year-old male presented with fatigue, weight loss, double vision and extra
      heart sounds].
AB  - BACKGROUND: The diagnosis of culture-negative endocarditis, defined as an active
      infection of the endocardium in the absence of positive blood cultures, is
      challenging. MATERIAL AND METHODS: A 34-year-old male presented with persistent
      fever and negative blood cultures. The echocardiogram showed a bicuspid aortic
      valve, severe aortic regurgitation, an abscess cavity in the aortic root, and a
      mass on the anterior leaflet of the mitral valve. The abscess cavity could be
      visualised only with transoesophageal echocardiography. RESULTS: The diagnosis of
      infective endocarditis could be established clinically with the Duke criteria.
      The echocardiographic findings were confirmed at surgery. Cultures of the excised
      tissue were negative, but histology showed strong evidence of infection.
      INTERPRETATION: The Duke criteria can be useful in the assessment of a clinical
      diagnosis in subjects with endocarditis and negative blood cultures.
      Transoesophageal echocardiography is especially important in this setting.

PMID- 15250118
TI  - Stem cell research: an ethical evaluation of policy options.
AB  - In February 2004, South Korean researchers became the first in the world to
      successfully harvest stem cells and establish a stem cell line from a cloned
      human embryo. This is just one of eight possible policy options concerning human
      embryonic stem cell research. In practice, every kind of stem cell research can
      be done in one country or another. This paper evaluates the eight policy options
      concerning human embryonic stem cell research in light of the arguments and
      decisions behind them.

PMID- 15250119
TI  - On the ethical evaluation of stem cell research: remarks on a paper by N.
      Knoepffler.
AB  - This response to Nikolaus Knoepffler's paper in the same issue of the Journal
      agrees that if the arguments supporting the first two of the eight human
      embryonic stem cell research policy options discussed are unsound, as Knoepffler
      argues, then it seems natural to move to the increasingly permissive options. If
      the arguments are sound, however, then the more permissive options should be
      rejected. It is argued that three of the rejected arguments, taken together,
      constitute very good reasons to hold that a human embryo is endowed with dignity
      from fertilization onward. Thus, countries that want their public policies to
      match the moral imperative of respect for human beings should refrain from
      allowing destructive human embryo research and should devote considerable energy
      and public funds to research and clinical trials using non-embryonic ("adult")
      stem cells.

PMID- 15250120
TI  - Creating a stem cell donor: a case study in reproductive genetics.
AB  - During the nearly 10 years since its introduction, preimplantation genetic
      diagnosis (PGD) has been used predominantly to avoid giving birth to a child with
      identified genetic disease. Recently, PGD was used by a couple not only to test
      IVF-created embryos for genetic disease, but also to test for a nondisease trait
      related to immune compatibility with a child in the family in need of an
      hematropoetic stem cell transplant. This article describes the case, raises some
      ethical and policy issues, highlights gaps in U.S. policy, and finally makes some
      recommendations for addressing advancing genetic and reproductive technologies.

PMID- 15250121
TI  - Stem cell research in the U.S. after the President's speech of August 2001.

PMID- 15250122
TI  - Evaluating the health-related quality of life effects of cochlear implants: a
      prospective study of an adult cochlear implant program.
AB  - This paper prospectively documents the health-related quality of life (HRQoL) and
      social participation benefits of adult patients receiving cochlear implants in
      Australia and New Zealand. Thirty-four consecutively implanted patients completed
      the Assessment of Quality of Life (AQoL) and Hearing Participation Scale (HPS)
      instruments before implantation, and at 3- and 6-month follow-ups. Implantation
      resulted in significant improvements in AQoL and HPS scores, The effect size was
      1.09 for both measures. Those in the top socio-economic tertile obtained the
      greatest gains. The HRQoL and social participation benefits were slightly larger
      than those reported elsewhere. This may be because participants used more recent
      technology (Nucleus 24 rather than Nucleus 22) and received auditory and self
      efficacy training as part of their rehabilitation. The results suggest that
      cochlear implants have a large beneficial effect. They show that social and HRQoL
      outcomes can be parsimoniously measured using the HPS and AQoL instruments.

PMID- 15250123
TI  - The effect of initial stimulus type for visual reinforcement audiometry.
AB  - Visual reinforcement audiometry (VRA) is routinely used with infants to assess
      hearing level. It is an operant procedure based on the association of auditory
      and visual stimuli. There are several recommended test procedures for VRA. One
      clinical VRA procedure involves presenting the initial auditory stimulus without
      activation of the visual reward. If the infant generates a head orientation
      response, the visual reward is then activated. The aim of this study was to
      investigate the unconditioned response rates (head orientation towards
      loudspeaker) to two different sound-field-presented stimuli, 1000-Hz narrowband
      noise (NBN) and 1000-Hz frequency-modulated tones (FMTs), using this VRA
      procedure. For each stimulus type, 100 infants presenting for VRA were assessed
      (age range 6-30 months, mean age 13 months). Of the infants presented with NBN,
      69% responded, compared to 25% of infants presented with FMTs. Chi-squared
      analysis revealed a highly significant statistical difference in favour of NBN.
      In conclusion, this study demonstrated the effectiveness of using a 1000-Hz NBN
      stimulus over a 1000-Hz FMT stimulus in securing an unconditioned head
      orientation response in infants presenting for VRA.

PMID- 15250124
TI  - Comparison of three procedures for initial fitting of compression hearing aids.
      III. Inexperienced versus experienced users.
AB  - We assessed whether gain requirements differ for experienced users and new users
      when fitted with multi-band compression hearing aids Three procedures for initial
      fitting were used: the Cambridge method for loudness equalization (CAMEQ), the
      Cambridge method for loudness restoration (CAMREST), and the desired sensation
      level input/output (DSL[i/o]) method. Twenty experienced hearing aid users and 20
      new users with mild-to-severe sensorineural loss were fitted with Danalogic 163D
      digital hearing aids, using each procedure in turn in a counter-balanced order.
      The new users were given a pre-fitting with slightly reduced gains prior to the
      'formal' fitting. Immediately after formal fitting with a given procedure, and 1
      week after fitting, the gains were adjusted by the minimum amount necessary to
      achieve acceptable fittings. The amount of adjustment required provided the main
      measure of the adequacy of the initial fitting. On average, new users required
      decreases in gain for all procedures, the decreases being larger for DSL[i/o]
      than for CAMEQ or CAMREST. For experienced users, gain adjustments were small for
      CAMEQ and CAMREST, but were larger and mostly negative for DSL[i/o]. After these
      gain adjustments, users wore the aids for at least 3 weeks before filling out the
      Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and taking part
      in laboratory measurements of the speech reception threshold (SRT) for sentences
      in quiet and in steady and fluctuating background noise at levels of 60 and 75
      dBSPL. The scores on the APHAB test and the SRTs did not differ significantly for
      the three procedures. We conclude that the CAMEQ and CAMREST procedures provide
      more appropriate initial fittings than DSL[i/o]. For inexperienced users, gains
      typically need to be reduced by about 3dB relative to those prescribed by CAMEQ
      or CAMREST, although the amount of reduction may depend on hearing loss. An
      analysis of gain adjustments as a function of order of testing provided some
      evidence for increased tolerance to high-frequency amplification with increasing
      experience during the 4-month course of the trial, but this effect did not differ
      for the experienced and new users.

PMID- 15250125
TI  - Changing characteristics of first-time hearing aid applicants in The Netherlands
      in the past decade.
AB  - This study assessed changes in the characteristics of first-time hearing aid
      applicants in the past decade. Age, gender, date, type and ear of first hearing
      aid and audiometry were determined for a sample of 705 first-time hearing aid
      applicants. Thirteen cohorts resulted, according to the year of first visit to
      the dispenser. Differences in age, hearing loss, gender and type and ear of first
      hearing aid between cohorts were analysed. The mean age of first-time hearing aid
      users increased from 59.52 years in 1987 to 71.84 years in 1999. The mean pure
      tone average hearing loss in the better ear (1, 2 and 4kHz) decreased from 69.06
      dB in 1987 to 51.86dB in 1999. Relatively more males than females were fitted
      with hearing aids. Our conclusions are that people are being fitted with hearing
      aids at older ages and with smaller degrees of hearing loss.

PMID- 15250126
TI  - Tinnitus impairs cognitive efficiency.
AB  - Many people who complain of tinnitus say that the noises impair their mental
      concentration. This complaint was investigated by self-report (primarily the
      Cognitive Failures Questionnaire) and by means of five cognitive tasks, four
      presented via laptop computer and one given manually. The tasks measured
      performance under single- and dual-task conditions and included tests of
      sustained attention, reaction time, verbal fluency and immediate and delayed
      memory. Two groups of outpatients attending audiological clinics (tinnitus, n =
      43; hearing impairment, n = 17) were compared with non-clinical volunteers (n =
      32). The results replicated earlier findings that tinnitus outpatients report
      significantly more everyday cognitive failures than do controls. The tinnitus
      group responded significantly more slowly than the two control groups on the
      variable fore-period reaction time task under dual-task conditions. In general,
      comparisons between the groups on other tasks showed equivalent performance, but
      both clinical groups performed more poorly than non-clinical controls on verbal
      fluency. We conclude that cognitive inefficiency in tinnitus participants is
      related to the control of attentional processes, consistent with our earlier
      theoretical speculation about the nature of tinnitus complaint and with published
      findings on the effects of chronic pain on cognitive processes.

PMID- 15250127
TI  - Monaural and binaural perception of approaching and withdrawing auditory images
      in humans.
AB  - Radial motion of the auditory image (approach or withdrawal) was modeled with the
      help of two loud-speakers placed at different distances from the listener in the
      anechoic chamber. The thresholds of sound duration for image motion and
      differential thresholds for its velocity at various azimuthal angles were
      studied. At azimuthal angles of 0 degrees, 30 degrees, 45 degrees, and 60
      degrees, the threshold values of the stimulus durations were 150-200 ms. At an
      azimuthal angle of 90 degrees from the head midline, it increased by about 25-30%
      as compared to other angles. In the case of monaural listening to the signals by
      unilaterally deaf subjects, the threshold durations of the sound signals were two
      to three times higher as compared to healthy subjects. Differential thresholds
      for calculated velocity of the radial motion have been measured within the range
      0.4-1.0 m/s, increasing with increase of the standard velocity from 3.4 to 6.9
      m/s.

PMID- 15250128
TI  - Influence of stimulus frequency on NRT recordings.
AB  - Research in neural response telemetry (NRT) with the Cochlear 'Nucleus' CI24M
      Implant began a few years ago, using the first NRT software version (2.04). It
      has been demonstrated that NRT offers possibilities for fitting the implant
      speech processor. NRT sessions, however, remain lengthy for the patients,
      especially for children, and NRT research is seeking to reduce session time. The
      new version of the NRT software (3.0) allows implant stimulation up to 400 Hz,
      whereas the previous version stimulated only up to 80 Hz. The time gained is very
      significant. The goal of the present study was to observe and assess the
      modifications in NRT produced by these higher stimulus frequencies. Growth
      functions were measured in six adult patients for electrodes 5-10-15-20 at
      frequencies of 20, 80, 150, 250 and 365 Hz to determine NRT thresholds (NRT-T).
      Subjective detection thresholds (T) were also measured for the same electrodes
      and frequencies. The results showed that the number of valid responses, like the
      quality and amplitude of the NRT response, quickly decreased at these higher
      rates. Consequently, the number of measurement points used for the growth
      function decreased with frequency. Moreover, when frequency increased, the T
      value decreased while NRT-T increased: the gap between the two thresholds
      increased with frequency in a linear manner common to all patients. The growth
      function slopes did not change significantly with frequency.

PMID- 15250129
TI  - [The effect of mechanical stimulation on the proliferation and synthetic function
      of osteoblasts from osteoporotic rat].
AB  - The purpose of this paper is to investigate that the effect of cyclic biaxial
      mechanical strain on proliferation and synthetic function in the osteoblasts
      isolated from 3 month-old normal female Sprague-Dawley (SD) rats and osteoporotic
      rats. The osteoblasts were cultured in F-12 medium contained with 10% fetal
      bovine serum (FBC) and grown to subconfluency in Flexercell apparatus in a
      humidified incubator with 5% CO2 and 95% air at 37 degrees C. Mechanical strain
      was applied to the cells for periods of 30 min, 2, 4 and 8 hours every
      day,lasting 2 days. The amplitude of mechanical strain applied to the cells were
      400, 1000 and 4000 microm strain respectively, at a frequency of one hertz (1 H).
      Unstrained cells were used as control. The results showed that proliferation
      activity of osteoblast in osteoporotic rats are higher than that in normal rats
      without mechanical strain the mechanical strain can elevate the proliferation
      activity and the synthetic function of osteoblast from normal rats at 400, 1000
      microm strain. However, the mechanical strain increased significantly the
      proliferation in the osteoblasts and suppressed obviously the synthetic function
      in the osteoblasts at 4000 microm strain. The mechanical strain don't affect the
      proliferation activity and the synthetic function of osteoblast from osteoporotic
      rats at 400 microm strain. The mechanical strain decrease the proliferation
      activity of osteoblast from osteoporotic rats at 1000 microm strain. The
      mechanical strain can elevate the proliferation activity and the synthetic
      function of osteoblast from osteoporotic rats at 4000 microm strain. In our
      study, the reaction of the osteoblasts from normal rats and osteoporotic rats to
      the mechanical stimulation suggested that there are more highly sensitive to the
      mechanical stimulation in the osteoblasts from normal rats than that from
      osteoporotic rats.

PMID- 15250130
TI  - [Development of artificial disc nucleus materials (semicrystalline polyvinyl
      alcohol hydrogel elastomers)].
AB  - For the purpose of developing of disc nucleus replacement (semicrystalline PVA
      hydrogel elastomers) and explorating the possibility of clinical application, in
      this study,the aqueous PVA solution froze at -20 degrees C for 6-12 h, and then
      thawed at room temperature for 1-2 h. The same process was repeated 1-3 times.
      After the specimen was dehydrated in vacuum, a kind of artificial disc nucleus
      materials (semicrystalline PVA hydrogel elastomers ) was formed. DSC and
      mechanical tests were conducted to investigate the influence of aqueous PVA
      solution concentration, of dehydrating in vacuum, and of gamma-ray irradiating
      upon the degree of crystallity and mechanical properties of PVA hydrogel
      elastomers.

PMID- 15250131
TI  - [Research on carboxymethyl chitosan acting as the adjuvant for implantable
      degradable microspheres].
AB  - As a kind of biomaterial, carboxymethyl chitosan (CMC) has excellent
      biodegradable and bioacceptable capabilities using. This study was aimed to probe
      into the feasibility of CMC to prepare the implantable sustained release
      Ciprofloxacin Hydrochloride (CPX) microspheres(MS), and to go further into the
      pharmaceutic technology, the morphology and the characteristics of in vitro
      release of the microspheres. First, we prepared the microspheres by
      emulsification and cross-linking technology. Then, scanning electron microscopy
      (SEM), infrared spectrum (IR) and differential thermal analysis (DTA) were used
      to detect the structure and morphology of the MS. The in vitro release of CPX/CMC
      MS and the CPX content of the MS were detected through continuous-flow releasing
      system. We found that the structure and morphology of the MS were affected by the
      conditions of preparation such as emulsification and cross-linking temperature,
      ionic strength and stirring speed, that the releasing time of CPX was more than 7
      days, and that the releasing behaviors of the microspheres conformed to the
      Higuchi model. So we drew the conclusions that CMC could be used as a kind of
      absorbable and implantable adjuvant for sustained release, the technology of
      emulsification and cross-linking was proved to be feasible, stable and simple.

PMID- 15250132
TI  - [Visualizing living fibroblast on co-cultured denture base resin by green
      fluorescent protein marker introduced into the cell].
AB  - Visualizing living cells growing on co-cultured biomaterials is ideal for
      material biocompatibility evaluation in vitro. In this experiment, mouse
      fibroblasts L929 were labeled by introducing the gene coding enhanced green
      fluorescent protein (EGFP) marker into the cells. Morphology as well as
      proliferation of labeled cells surrounding or on the surface of co-cultured
      denture base resin slides were observed by use of phase-contrast microscope and
      fluorescent microscope directly. It was found that residual methyl methacrylate
      (MMA) in the denture base resin exhibited transient cytotoxicity to fibroblasts
      and this transient cytotoxicity could be eliminated by pre-extracting the resin
      with ddH2O for a short time. This fact demonstrated that even slight cytotoxicity
      of materials could be detected through imaging of living cells near material or
      material touched. And it was suggested that imaging of living cells co-cultured
      with biomaterial is helpful to understanding biocompatibility of materials more
      accurately.

PMID- 15250133
TI  - [Biomechanical study of medical hard tissue adhesive bonding butterfly fracture
      fragment in middle part of fresh human tibia].
AB  - A medical hard tissue adhesive, octyl-a-cyanoacrylate, was tested in 6 fresh
      human tibiae. A 90 degrees butter-fly fracture fragment was made in the middle
      part of tibia by bandsaw. The compressive stress, torsional stress and angular
      deflection were assessed before and after osteoectomy respectively. After
      adhesive bonding, the compressive stress, torsional stress and angular deflection
      were tested again. The butterfly fracture fagment decreased the bending strength,
      torsion strength, yielding strength of tibia bone. In torsion test, the torque of
      tibia before osteoectomy is greater than bonded tibia, the bonded tibia is
      greater than that of the unbonded tibia. In compression test, before adhesive
      bonding broken, the compressive curve slope of tibia before osteoectomy is
      greater than that of bonded tibia, the bonded tibia is greater than that of the
      unbonded tibia. In angular deflection test before adhesive bonding of broken,the
      curve slope of tibia before osteoectomy is not different from that of bonded
      tibia (P>0.05), the slope the bonded tibia is greater than the slope of unbonded
      tibia(P<0.05). The elastic modulus, rigidity coefficient and moment of area
      inertia show no statistical difference between the bonded tibia and intact tibia.
      The used of medical hard tissue adhesive to bond the fracture fragment could
      improve the bending strength, torsion strength, yielding strength of tibia bone.
      In operation, it can reduce the soft tissue injury when the fracture fragment is
      being fixed, and this will benefit bone healing.

PMID- 15250134
TI  - [Force-dependent effects of interleukin-8 production in endothelial cells exposed
      to fluid shear stress].
AB  - Fluid shear stress plays a key role in many physiological activities and
      pathological processes of the cardiovascular diseases. In vivo, endothelial cells
      (ECs) are constantly exposed to hemodynamic force which can modulate structure
      and function of ECs. Previous studies have demonstrated that IL-8 protein
      production in endothelial cells was modulated by fluid shear stress, and IL-8
      protein production induced by fluid shear stress was time-dependent. In order to
      identify the role of intensity of fluid shear stress on IL-8 protein production
      of human umbilical vein endothelial cells (HUVECs), we had HUVECs exposed to
      shear stress 2.09, 4.61, 6.19, 8.51, 10.50, 12.59, 14.41, 17.22, 18.32 dyne/cm2
      respectively and employed quantitative sandwich enzyme-linked immunosorbent assay
      (ELISA) to measure the IL-8 protein. Here we show that HUVECs untreated with
      fluid shear stress secreted very little IL-8 in culture media. The IL-8 protein
      production induced by shear stress was force intensity-dependent. After HUVECs
      being subjected to low fluid shear stress (2.09 dyne/cm2) for 5 h or 6 h, IL-8
      protein production increased and was nearly 6 times or 7 times over that of
      HUVECs subjected to high fluid shear stress (18.32 dyne/cm2). The linear
      regression equations between IL-8 protein production (y) and shear stress
      (dyne/cm2, x) are y=760.12-36.06x, gamma=-0.978 (for 5 h); y=781.87-36.66x,
      gamma=-0.980 (for 6 h). This in vitro study demonstrates that the production of
      IL-8 can be regulated by fluid shear stress, and the production of IL-8 induced
      by shear stress is not only time-dependent but also force intensity-dependent.
      These observations suggest that the low fluid shear stress induces much more IL-8
      secretion, which may play an important role in the pathogenesis and development
      of both inflammation and atherosclerosis.

PMID- 15250135
TI  - [Numerical verification of the analytic solution of electrical potential in a
      homogeneous conducting sphere in numerical value].
AB  - Since the 1980s, the research of non-trauma orientating based on EEG has been
      developed considerably. Especially, the method of equivalent moving dipole model
      has been applied to analysis of EEG. In this article, reference to some scholars'
      work, we deduce the analytic solution of electrical potential in a homogeneous
      conducting sphere (the positions of multiples are discretional in the sphere
      model), and then verify its accuracy by some collected data.

PMID- 15250136
TI  - [Using the histogram analysis method to assess the time-frequency features of rat
      EEG under different vigilance states].
AB  - To investigate the non-stationary time-frequency features in rat
      Electroencephalogram (EEG) under different vigilance states, the methods of multi
      resolution wavelet transform (WT) and statistical histogram analysis were used.
      EEGs of the freely moving rats were recorded with implanted electrodes under the
      vigilance states of waking, slow wave sleep (SWS) and rapid eye movement sleep
      (REM). The EEGs were firstly decomposed into four frequency components of delta,
      theta, alpha and beta by using multi-resolution wavelet transform. Then, the
      parameters of mean value, standard deviation, skewness and kurtosis of the
      logarithm power histograms and the power percentage histograms of each of the
      frequency components were calculated. The results showed that the distributions
      of the logarithm power histograms were not quite different from the normal
      distribution. However, most of the power percentage histograms were significantly
      different from the normal distribution. The results of one-way ANOVA indicated
      that there were significant differences in the parameter values of the histograms
      both among different states and among different frequency components. Moreover,
      Skewness and kurtosis of the logarithm power histograms of some characteristic
      waves in EEG, such as delta wave during SWS and theta wave during waking and REM,
      obtained high values. Thus, the histogram parameters of EEG WT components might
      become as quantitative measures to describe the dynamic time-frequency features
      of EEG.

PMID- 15250137
TI  - [A three dimensional fractal simulation of the lung bronchial tree].
AB  - The lungs are naturally irregular and asymmetrical organ in anatomy. The
      conducting bronchial trees in the lungs display complex self-similar structure.
      We have established the host mesh coordinates of the right lung on the basis of
      the anatomical data from the literature. A three-dimensional fractal model of the
      conducting airways was set up by calculating the coordinates of the mass centers
      of the divided blocks, searching the branch direction and determining branch
      lengths with the use of the drawing tool OpenGL. Specific data of the lengths at
      various grades, branching angles, and capillary diameters were obtained. As a
      result, the computed data were identical with those of the existing statistical
      data. The fractal covering dimensionality obtained in the computation of this
      model was 2.19, which is very close to the ideal dimensionality, 2.17, from the
      literature. The present model has laid the foundation for further research of the
      gas diffusion and transfer performance in the lungs using the fractal concept,
      and furthermore, it helps to save the computer memories and fastening the graphic
      transfer.

PMID- 15250138
TI  - [Mechanical response numerical analysis of bone tissue based on liquid saturated
      biphasic porous medium model].
AB  - A biphasic porous medium model based on the mixture theory in continuum mechanics
      frame was used to depict the distributions of osseous stress field, distortion
      field and pore pressure when the bone tissue was subject to various dynamic
      loads. In the model, the bone tissue was considered as a transversely isotropic,
      liquid saturated porous material. The coupling relationship among the distortion,
      fluid flow and the streaming potential is studied. The Galerkin weighted residual
      method was used to derive the finite element formulation for dynamic response and
      the streaming potential calculating formulation of bone tissue, the penalty
      finite element formulation was obtained via introducing the ratio term of
      pressure p and penalty parameter beta in the continuity equation and, in turn,
      eliminated the pressure term in governing equation sets. The computational
      results show that the viscoelastic behavior and the energy dissipation property
      in the bone tissue, especially in the cancellous bone, is caused to a great
      extent by the pore liquid flow and diffusion. Meanwhile, because of the existence
      of electrical double layer between the solid phase and liquid phase, when the
      liquid constituents in the pore diffuse, the streaming potential appears, and the
      growth and absorption of bone tissue is expedited.

PMID- 15250139
TI  - [Application of image correction in 3D reconstruction of mandible from CT
      slices].
AB  - Precision registration of serial sections is an important step for 3-D image
      reconstruction. It directly affects the accuracy of the reconstructed result and
      parameter computation. This problem has been studied and demonstrated by many
      investigators, but the whole process has not yet reached good performance. In
      this paper, we discussed the registration of serial sections image of mandible
      and put forward a method of the soft registration-based transformation on the
      basis of the hard registration in consideration of the speciality of 3-D image
      reconstruction for the serial sections of mandible. Employing control points and
      using Affine Transformation and Extended Hough Transformation, we solved the
      problem of displacement on 3-D image reconstruction for serial secons and paved
      the way for reconstructing the mandible microstructure with reality. The results
      of experiments indicate that the 3D image reconstructed after registration has
      only a little distortion.

PMID- 15250140
TI  - [Research and implementation of picture archiving and communication system (PACS)
      based on B/S mode].
AB  - In this paper, with B/S application and architecture, an integrated solution of
      PACS is designed, and the function and application of each part of PACS based on
      the architecture is introduced. The PACS based on this mode is safe, stable, easy
      to manage and upgrade and convenient for use in telemedicine.

PMID- 15250141
TI  - [Autoregressive model order property for sleep EEG].
AB  - Traditional sleep scoring system describes the sleep EEG characterized by
      features in time domain as well as frequency domain. Power Spectral Density (PSD)
      is one of the well-used methods to observe the occurrence of specified rhythms.
      However, the parameter model based PSD estimation is used with the assumption
      that the model order is determined as low as possible through prior knowledge.
      This paper briefs the development of Autoregressive Model Order (ARMO) criterion,
      and provides the distribution of ARMOs for specified sleep EEG, which shows that
      ARMOs concentrate on several well separated regions that are indicative of the
      microstructure and transition states. This study suggests the promising
      perspective of ARMO as a special EEG feature for weighing complexity, randomness
      and rhythm components.

PMID- 15250142
TI  - [Feature extraction and classification of EEG for mental tasks based on wavelet
      packet analysis].
AB  - This paper explores the use of wavelet packet analysis to extract features from
      spontaneous electroencephalogram (EEG) during three different mental tasks.
      Artifact-free EEG segments are transformed to multi-scale representations by
      dyadic wavelet packet decomposition channel by channel. Their feature vectors
      formed by energy values of different sub-spaces EEG components are used as inputs
      of a radial basis function network to test the classification accuracies of three
      task pairs. The results indicate that the classification accuracies of the
      wavelet packet analysis method are significantly better than those of
      autoregressive model method. Wavelet packet analysis would be a promising method
      to extract features from EEG signals.

PMID- 15250143
TI  - [Separating independent components in heart period signal].
AB  - To extract sub-signal of heart period signal (HPS), a new statistical signal
      processing approach, namely independent component analysis (ICA) was addressed.
      Electrocardiosignal (ECS) was acquired from ten volunteers. ECS was sampled 8
      minutes when the volunteer was in supine position, and then when the same
      volunteer was in erect position. HPS was extracted from ECS. According to time
      delay, HPS was divided into five groups as mixed signals. Five signals were
      reconstructed into two groups by ICA. The rebuilt signals were transformed by
      Fourier transformation. One centralized in low frequency (called IC1); the other
      did in high frequency (called IC2). The power of IC1 was significantly increased
      (P<0.01) while that of IC2 showed no significant change (P>0.05), and the ratio
      of IC1 to total power also significantly increased with the change from supine
      position to erect position. Comparsion between the two postural results reveals
      that IC1 may express sympathetic activity, and IC2 represents parasympathetic
      activity. Sympathetic and parasympathetic nervous functions can be evaluated
      respectively and quantitatively by use of data and graphs from the two decomposed
      components.

PMID- 15250144
TI  - [Study of 3D visualization methods on PACS workstation].
AB  - Based on a discussion on PACS and the way its image workstation obtains scanned
      sequential images, this paper presented a method of 3D surface construction and
      visualization on PACS workstation. Guest/Server structure was used between PACS
      application entities. Image storing and transmission were realized by service
      classes established by DICOM standards. Relation database was used to arrange the
      stored sequential images. Image workstation transformed the sequential images
      obtained from PACS net into volume data field. 3D reconstruction and rendering
      results were obtained by using surface-rendering and volume-rendering methods,
      which made the 3D construction results acquire vivid 3D structure details of high
      fidelity and strong sense of reality. 3 sets of application results were also
      presented in this paper.

PMID- 15250145
TI  - [Evoked potentials extraction based on cross-talk resistant adaptive noise
      cancellation].
AB  - As Evoked Potentials are much lower in amplitude with respect to the on-going
      EEC, many trigger-related signals are needed for common averaging technique to
      enable the extraction of single-trail evoked potentials (EP). How to acquire EP
      through fewer evocations is an important research project. This paper proposes a
      cross-talk resistant adaptive noise cancellation method to extract EP. Together
      with the use of filtering technique and the common averaging technique, the
      present method needs much less evocations to acquire EP signals. According to the
      simulating experiment, it needs only several evocations or even only one
      evocation to get EP signals in good quality.

PMID- 15250146
TI  - [An experimental system of induced-current EIT].
AB  - Induced-current electrical impedance tomography (ICEIT) is a newly hot research
      field in electrical impedance tomography (EIT) because of its advantages of
      contactless exciting. A preliminary ICEIT system with 3 excitation coils has been
      accomplished. It includes the constant current source (CCS), power amplifiers,
      excitation coils,physical phantom, measurement-mode setting circuit, signal
      measuring block, DAC and digital I/O card. The CCS is accomplished with Direct
      Digital Synthesis (DDS) technique. Its frequency is 46.875 KHz. Its output
      current is divided into 16 steps from 0.16 mA to 2.56 mA which can be set by
      computer. The three driving coils have the same diameter of 50 cm, each coil's
      inductance is 193.5 microH. The power amplifier can provide 800 mA driving
      current (f = 46.875 KHz) to the coil under +/- 25 V power supplying. The signal
      from measurement electrodes is switched to measurement channel which includes IA,
      BP filter and synchronized demodulator, then the analog signal is converted to
      digital signal by a 12b A/D Card and the data is acquired by DMA mode. Our
      experiments show that a distinguish change of signal from the surface electrodes
      can be acquired by the experimental system when different objects are placed in
      the physical phantom. And 3 x 31 signals for preliminary imaging have been
      acquired.

PMID- 15250147
TI  - [Long-term toxicity test of arginine esterase from Agkistrodon halys ussuriensis
      venom].
AB  - To study the long-term toxicity of arginine esterase from Agkistrodon halys
      ussuriensis venom for the clinical application of arginine esterase in the
      future. Beagle dogs were used as experimental animals and were divided into
      control group, arginine esterase low dose group (0.06 u/kg), the middle dose
      group (0.18 u/kg) and high dose group (0.36 u/kg). Every group consisted of four
      dogs. The arginine esterase was given intravenously once a day for 180 days. Then
      three dogs in each group were sacrificed and the fourth one was fed without
      injecting arginine esterase for 15 days. The toxic reactions during treatment and
      recovery period were determined by evaluating and comparing the general criteria
      ( including locomotor activity, growth rate, appetite and death rate), clinical
      criteria (including blood test and urine test), pathological dissection and
      viscera coefficient of the treated animals and the control animals. There were no
      significant differences in general criteria. The clinical criteria of the treated
      animals were the same as those of the control animals except liver function.
      There were no significant differences in pathological dissection and viscera
      coefficient between the treated animals and the control animals except livers.
      The livers in high dose arginine esterase treated animals were swollen and
      vacuolated and there was significant difference in liver coefficient between them
      (P<0.05). The toxic symptom of liver disappeared after withdrawal of treatment.
      From these results, the non-toxic dose of arginine esterase for dogs was
      estimated to be 0.18 u/kg under the present study conditions and is about 15
      times the clinical dosage for using the drug "Qingshuanmei" of which the main
      component is arginine esterase. The long-term toxicity test result indicates that
      the toxicity of pure arginine esterase is lower than that of "Qingshuanmei",
      suggesting that clinical use of the arginine esterase is safe.

PMID- 15250148
TI  - [Construction of the recombinant adenovirus vector carrying antisense multidrug
      resistance (MDR1) gene].
AB  - The fragment of MDR1 gene obtained from the plasmid pHaMDR1-1 carrying the whole
      human MDR1 cDNA, was cloned reversely into the shuttle plasmid pAdTrack-CMV. With
      the resultant plasmid and the backbone plasmid pAdEasy-1, the homologous
      recombination took place in the Escherichia coli BJ5183 and the recombinant
      adenoviral plasmid was generated. The adenoviruses were packaged in the 293
      cells. The recombinant adenovirus MDR1 vector would introduce the antisense MDR1
      gene into the human multidrug resistance hepatocellular cell line effectively,
      which would provide an experimental basis for studies on the multidrug resistance
      in human hepatocellular carcinoma.

PMID- 15250149
TI  - [Studies on herpes simplex virus thymidine kinase gene and GCV system for
      treatment of human bladder carcinoma].
AB  - To investigate the antitumor effect of herpes simplex virus thymidine kinase (HSV
      TK) gene/ganciclovir (GCV) system on human bladder cancer cells (T24), a
      retroviral vector with the gene (pLXSN-TK) was transduced into the packaging cell
      line PA317. A nude mouse model with human T24 was established to examine the in
      vivo efficacy. The animals were randomly assigned to two treatment groups and two
      control groups. Treatment I and Treatment II were given in situ injection of
      virus suspension and PA317/TK respectively, followed by treatment with GCV for 14
      days. Control I and Control II were given in situ injection of same volume of
      normal saline and PA317/TK respectively, followed by treatment with GCV and with
      normaly physiologic saline respectively for 14 days. The weight and the volume of
      tumor were measured. HSV-TK mRNA expression was determined by hybridization in
      situ. Cell apoptosis was evaluated by flow cytometry (FCM) and termininal
      deoxynucleofidyl transferase-mediated dUTP nick end labelling (TUNEL) technique.
      The results showed: (1) In vivo, the retrovirus transferred HSV-TK gene can be
      transduced into human bladder cancer cell T24. The tumors in T24 mice with TK
      gene transduced were much smaller than those in other groups. (2) After treatment
      with HSV-TK/GCV, the phenomenon of bladder ceancer cell apoptosis was more
      conspicuous as compared with that of other groups. Therefore, HSV-TK/GCV system
      can suppress the growth of T24 in vivo and may relate to "bystander effect". It
      could be a valuable therapy for human bladder cancer.

PMID- 15250150
TI  - [Effect of steep pulsed electric fields on survival of tumour-bearing mice].
AB  - To investigate the lethal effect of steep pulsed electric fields (SPEFs) on
      cancer cells and the life-prolonging effect of SPEFs on the survival of tumour
      bearing mice, this study was carried out with the use of SPEFs to treat 40 BALB/C
      mice inoculated by cervical cancer. The lethal effect on cancer cells and the
      life-prolonging effect on tumour-bearing mice were examined and compared between
      the experiment group and control group. The survival periods of the experiment
      group and control group were 52.05 days and 33.03 days, respectively. There was a
      significant difference in survival curve between the two groups. The results
      confirmed the inhibitiory effect and lethal effect of SPEFs on cancer cells.
      SPEFs can prolong the survival period of tumour-bearing mice.

PMID- 15250151
TI  - [Rheological characteristic of microemulsion including phosphatidycholine].
AB  - This study aimed to evaluate the rheological characteristic of W/O microemulsion.
      Using the Low Shear-30 Sinus Rheometer, we assessed the effects of water
      percentage in microemulsion on the apparent viscosity of microemulsion at
      different shear rates and temperature, and on the viscoelasticity of
      microemulsion. The results demonstrated that with the increase of water, the
      apparent viscosities at four different shear rates increased exponentially. The
      fitted curve between water percentage and the apparent viscosity (eta) at low
      shear rate was steeper than the others. We found that viscous component (eta')
      and elastic component (eta") also increased exponentially when water percentage
      was increasing. This communication addressed the relationship between water
      percentage and eta, and discussed the physical meaning of the elastic component.
      The results suggest that both the viscous component and the elastic component
      present qualitatively physical nature, but the viscous component is more accurate
      than the other.

PMID- 15250152
TI  - [Human gastric tissues coexpress two different splicing cholecystokinin-B/gastrin
      receptors].
AB  - This study was conducted to explore whether cholecystokinin-B/gastrin receptor
      (CCKBRwt) gene and its alternative splicing variant (CCKBRi4sv) are expressed in
      human gastric carcinomas cell line and tissues, and to find out their
      relationship with the development and progression of human gastric carcinoma. The
      mRNA expression levels of CCKBRwt and CCKBRi4sv were detected in 30 human gastric
      carcinomas and normal tissues adjacent to cancer, 10 gastritis specimens, 2
      autopsied normal stomach specimens as well as in a gastric carcinoma cell line
      SGC-7901 cells. The results revealed that the transcripts of CCKBRwt and
      CCKBRi4sv were observed in all of the human gastric specimens tested, but only
      CCKBRwt was expressed in gastric cancer cell line SGC-7901 cells. The expression
      levels of the two receptors were not correlated with the differentiation and
      metastases of gastric cancers. From the results, we infer that human gastric
      tissues simultaneously express CCKBRwt and CCKBRi4sv, and CCKBRi4sv may have
      unknown physiological functions in gastric epithelial cells.

PMID- 15250153
TI  - [Experimental research into the inhibitory effect of 131I-recombinant human
      epidermal growth factor on the growth of breast cancer in vivo].
AB  - This experiment was designed to study the effect of 131I-recombinant human
      epidermal growth factor (131I-rhEGF) on the growth of tumor in nude mice loaded
      with human breast cancer. Bioactivity of 131I-rhEGF and uptake of 131I-rhEGF in
      breast cancer tissue were verified using biodistribution experiment of 131I-rhEGF
      in the nude mice loaded with human breast cancer. The effect of 131I-rhEGF on the
      growth of tumor was assessed via the growth experiment of tumor in the nude mice
      loaded with human breast cancer. The ultrastructural change of the tumor cell
      treated with 131I-rhEGF was observed under transmission electron microscope, and
      the pathological change of the tumor tissue treated with 131I-rhEGF was detected
      by biopsy. The results showed that the tumor tissue of nude mice bearing human
      breast cancer obviously takes in 131I-rhEGF; that intravenous administration and
      intratumoral administration of 131I-rhEGF both obviously inhibit the growth of
      tumor, the inhibition rates (82.00% and 80.70%) being remarkably higher than that
      of 131I (7.49%) and that of 131I-HSA (6.91%) (P<0.05); and that intravenous and
      intratumoral administration of 131I-rhEGF both obviously damage and kill tumor
      cells. Therefore, 131I-rhEGF can inhibit the growth of human breast cancer cell
      in nude mice; it is a potential receptor-mediated radioactivity targeting drug
      for treating breast cancer.

PMID- 15250154
TI  - [FTIR spectroscopy studies on the apoptosis-promoting effect of TFAR19 on the
      erythroleukemia cell line MEL].
AB  - The changes in the cellular main components of the mouse erythroleukemia cell
      line MEL for TFAR19 gene transfection were studied by the technology of Fourier
      transform infrared spectroscopy (FTIR). Using the method of gene transfection
      with liposome, we obtained MEL-TF19 cell line, which stably carries TFAR19, a
      novel apoptosis-related gene. The expression of the gene on mRNA level was
      confirmed by RT-PCR. Then, FTIR spectra of the cells were measured in the course
      of apoptosis induced by serum deprivation. Our results indicated that after being
      transfected with TFAR19 gene, MEL-TF19 cells exhibited relatively higher protein
      content, higher transcriptional activity, and relatively lower phospholipid
      content as compared with those exhibited by MEL cells. All the above changes
      reflect the apoptosis-promoting effect of TFAR19 gene, and maybe account for the
      cellular rheological changes after TFAR19 gene transfection, which were
      discovered in our previous study.

PMID- 15250155
TI  - [A scheme for solution of hospital's data backup system].
AB  - In this paper, the implementation scheme for a hospital's data backup and
      recovery is introduced. It analyzes the goal of system design: to build a
      centralized, policy-based administration, automatic and high efficient data
      backup system.

PMID- 15250156
TI  - [On excellent education mode of biomedical engineering in USA].
AB  - Based on the rankings of the best undergraduate/graduate biomedical engineering
      programs from the USA News & World Report, we have made a comprehensive analysis
      on the excellent education mode in USA 2002. It is hoped that the results as
      reference materials will be useful to our biomedical education at home.

PMID- 15250157
TI  - [Development of a freezing drier for lyophilization of biomaterials].
AB  - To observe and assess the performance and effect of our self-made FD-1 freezing
      drier on biomaterials. R502 compressor and R502 refrigerating agent were adopted.
      In the experiment, FD-1 lyophilized collagen sponge, strain and defibrinogenase.
      The evaporating-condenser temperature reached -45 degrees C and the small icebox
      temperature reached -30 degrees C under the loading or free-loading circumstances
      in the lyophilizing box. The lyophilized collagen sponge had many pores in the
      structure, and the strain and the defibrinogenase were lyophilized and maintained
      satisfactorily. This freezing drier is suitable for lyophilizing some biomaterial
      samples in small or medium batches.

PMID- 15250158
TI  - [Visualization of EIM simulation data on real cardiac model].
AB  - Although 3D heart and torso model with realistic geometry are the basis of
      simulation computation in LFX Virtual Cardiac Model, the simulation results are
      mostly output in 2D format. Voxel mapping method is presented to solve this
      problem and extend the function of LFX Virtual Cardiac Model. Excitation
      Isochrone Map (EIM), one of the most important simulation results, was mapped
      from cardiac model with realistic geometry to real Visible Man cardiac model,
      then the EIM simulation data before and after mapping were visualized in the
      4DView which is a real-time 3D medical image visualization platform. With this
      method, the output format of EIM simulation data of LFX Virtual Cardiac Model was
      extended from 2D to 4D (time is the 4th dimension) and from cardiac model with
      realistic geometry to real cardiac model. According to the EIM simulation data
      visualization results before and after mapping, the LFX virtual cardiac model
      shows its characteristics with more realistic and effective simulation.

PMID- 15250159
TI  - [Pulse signal processing based on continuous wavelet transform].
AB  - Using the common algorithm and the Mellin algorithm of a continuous wavelet
      transform, we analyzed the pulse signals of 15 heroin addicts and 15 normal
      persons. With the use of two algorithms, every pulse signal was processed under 4
      scales. From the analyzed results, we found that there was significant difference
      of wavelet transform coefficients in the time interval 0.2 to approximately 0.4
      seconds between the heroin addicts and normal persons. In this paper, the
      critical parameter used to classify heroin addicts and normal persons is given to
      every algorithm. The research result of this paper shows that the continuous
      wavelet transform is really an effective method for processing pulse signals.

PMID- 15250160
TI  - [Development of a new noninvasive blood sugar detector].
AB  - The level of blood sugar is an improtant indicator used in the diagnosis and
      management of diabetes mellitus. In this respect, polarimeter and blood sugar
      detector were conventionally and generally used in hospitals; However, the former
      one is already obsolete; the latter one is invasive. In this paper, the
      development of a novel noninvasive blood-sugar detector is described. The
      experiment indicate that this detector is nonivasive, safe, fast, and easy to
      operate, and it can be of wide application.

PMID- 15250161
TI  - [Methods for the pre-treatment of biological tissues for vascular scaffold].
AB  - Today, the blood vessel substitutes are in large demand for coronary and
      peripheral bypass procedures, and the demand cannot be met by conventional
      sources. This problem will be solved by applying tissue-engineered blood vessel
      in clinics. The prefabrication of vascular scaffold will be involved in
      engineering a blood vessel substitute. Biological tissues are important
      biomaterials fabricating vascular scaffold which can offer better constructs for
      adhesion and growth of cells onto synthetic materials. Because of immediate
      degradation of biological tissues obtained from the abattoir, cadaver or patient
      and the presence of antigenicity in allogenic or xenogenic tissues, the fresh
      biological tissues can not directly be preserved and applied. The use and
      preservation of these natural biomaterials have typically required pre-treatment
      aimed at (1) reducing the antigenicity of the materials, (2) enhancing the
      resistance of the materials to enzymatic degradation, (3) stabilizing the
      structure of the tissues and maintaining their mechanical properties. Physical
      and chemical methods for the pre-treatment of biological tissues are available.
      The predominant chemical agents that have been investigated for the pre-treatment
      of biological tissues for vascular scaffold are glutaraldehyde, polyepoxy
      compound, carbodiimide, genipin and proanthocyanidin. Typical and particularly
      promising physical pre-treatment of biological tissues for vascular scaffold is
      dye-mediated photooxidation. The crosslinking mechanisms of all classes of pre
      treatments and the effects of pre-treatments on antigenicity, biostability,
      mechanical properties, cytoxicity and calcification of treated tissues are
      described in this article. The advantages and disadvantages of all pre-treatments
      are also reviewed. The trend of pre-treatment of biological tissues is to
      investigate and exploit the naturally occurring crosslinking reagent with less
      cytoxicity. Meanwhile, dye-mediated photooxidation crosslink is also a promising
      pre-treatment which should be widely applied in vascular scaffold.

PMID- 15250162
TI  - [Application of MEMS microneedles array in biomedicine].
AB  - Microneedles array based on micro electro-mechanical system (MEMS) technology is
      one of important applications in biomedicine and brings a new means in
      biomedicine field. The prospect for the development of microneedles technology in
      precision drug injection, clinical monitoring and biochemistry test is and save
      broad. This paper describes three important applications of MEMS microneedles
      array in biomedicine field: biomedicine microneedles electrode, transdermal
      delivery of drugs and fluid extraction, and then summarizes their application
      elements and recent development. It explains the characteristics of microneedles,
      which provide painless, effective and save biomedical method in accordance with
      human requirements. In addition, a series of the fabrication technology of
      microneedles array is discussed.

PMID- 15250163
TI  - [The algorithms and development for the extraction of evoked potentials].
AB  - The extraction of evoked potentials is a main subject in the area of brain signal
      processing. In recent years, the single-trial extraction of evoked potentials has
      been focused on by many studies. In this paper, the approaches based on the
      wavelet transform, the neural network, the high order acumulants and the
      independent component analysis are briefly reviewed.

PMID- 15250164
TI  - [Current aspects in red blood cell substitutes].
AB  - Red blood cell substitutes are a group of oxygen carriers designed to temporarily
      replace transfused blood. Current developing products include perfluorocarbon
      based and hemoglobin-based oxygen carrier. Each product is unique in its
      limitations and advantages. A number of products are in advanced clinical trials
      and nearing market. When they are available for use it is likely that development
      will accelerate and even better products will substantially alleviate the world
      wide shortage of blood for transfusion.

PMID- 15250165
TI  - [Development of polymeric nanoparticles in the targeting drugs carriers].
AB  - This review presents the most outstanding contribution in the field of polymeric
      nanoparticles used as targeting drugs delivery systems. Nanoparticles barrier is
      a novel kind of controlled release system for drugs which can effectively deliver
      the drug to a target site and increase the bioavailability and therapeutic
      benefit, while minizing the side effects. In this paper the applications of
      nanoparticles in the active, passive and physical targeting drugs carriers are
      reviewed.

PMID- 15250166
TI  - [Bioreactors for animal cell culture and their mechanical environment].
AB  - Bioreactor is a key device during in vitro animal cell culture. It provides an
      appropriate growth environment for the cells, enabling them to proliferate and
      become the final bio-product. Since animal cells are different from microbial
      cells in morphology, culture skill needed, and mechanical stimulation needed, the
      traditional microbial bioreactors are not suitable for the large-scale animal
      cell culture any more, and many new bioreactors are developed. This paper reviews
      the bioreactors particularly designed for the animal cell culture, and addresses
      the mechanical loads on the cultured cells.

PMID- 15250167
TI  - [Long-term effects and complications of intravascular brachytherapy].
AB  - Since the introduction of percutaneous transluminal coronary angioplasty,
      restenosis has remained the most challenging problem facing interventional
      cardiologist. Intravascular radiation is a feasible and promising adjunctive
      therapy in restenosis treatment by suppressing both neointimal proliferation and
      constrictive remodeling, while there are growing concerns about its long-term
      effects and complications in clinical perspectives as well as dosing and
      paradoxical stimulation. Current comments on them may well favor the choice of
      comprehensive treatment protocol for clinicians.

PMID- 15250168
TI  - [Progress of model organism genome].
AB  - This paper presents a description of the rules of construction and function of
      genome as well as evolutional relationship between organisms, and opens out the
      essence of life through introducing the progress in genome of model organism. The
      other purpose of this review is to highlight the status and function of model
      organism in the research of comparing genomics so as to provide the model of
      cycle for researches into high creature life, especially human beings life.

PMID- 15250169
TI  - [Progress in the treatment of stained teeth].
AB  - The treatment of stained teeth has been one of the striking aspects of
      stomatology and esthetic dentistry. Based on detailed data and references, this
      article introduces the types of stained teeth and the main treatment methods
      including strong point, weakness, limitation of the usage, result, and the
      relevant mechanisms. It addresses the researches on problems in the treatment of
      stained teeth. Also in this paper is envisaged what will be done to treat the
      stained teeth in future.

PMID- 15250170
TI  - [Neovascularization after ischemic stroke].
AB  - After ischemic stroke, there is neovascularization around the infarcted area,
      which is called penumbra. Angiogenesis and arteriogenesis are responsible for the
      new vessel formation. Until recently, vasculogenesis has been proved to involve
      mechanisms in postischemic neovascularization, which was thought to be restricted
      to embryonic development. New blood vessels' formation is a complex pathologic
      process after ischemic stroke, in which many factors are properly involved. There
      are factors stimulating neovascularization, such as vascular endothelial growth
      factor, platelet-derived growth factor, basic fibroblast growth factor and
      angiopoietin; there are also factors inhibiting neovascularization, such as
      thrombospondin. Functional recovery was found after stroke, which may contribute
      to angiogensis in the periinfarct tissue. Thus, therapeutic angiogenesis has been
      initially studied in animal models, but there is still a long way to go for
      therapeutic angiogenesis to be used in the treatment of stroke patient.

PMID- 15250171
TI  - CA medical group enhances capitation management oversight.

PMID- 15250172
TI  - CA physician groups develop integrated approach to chronic disease care for
      capitated patients.

PMID- 15250173
TI  - Affinity Health Plan pays capitated doctors for preventive services.

PMID- 15250174
TI  - [Effectiveness of three whitening dentifrices].
AB  - Over the past years the market share of whitening dentifrices has been
      increasing. The aim of this parallel, randomized, double-blind clinical trial was
      to assess the efficiency of three commercially available tooth whitening
      dentifrices. Thirty-six subjects with extrinsic tooth stain (A3 and darker) were
      randomly assigned to three groups (A, B, C) of twelve subjects each. Group A
      brushed their teeth twice daily with Durodont medical fresh and white (RDA 70),
      Group B with Friscodent Zahnweiss (RDA 87) and Group C with a combination of
      Durodont Zahnweiss intensiv (RDA 166) and Durodont medical fresh and white. At
      baseline and after four and eight weeks the color of the anterior teeth was
      evaluated using a VITAPAN classical color shade and a special colorimeter
      (Homeba). The colors of the shade guide were arranged and nummerized by value.
      After four and eight weeks of use each dentifrice showed a significant whitening
      effect compared to baseline (p < or = 0.05). There were, however, no significant
      differences between the groups. Moreover both methods showed similar results.
      Thus, the results support a significant "whitening" effect of all three
      dentifrices.

PMID- 15250175
TI  - [Indications for oral implantology in a referral clinic. A three-year
      retrospective analysis of 737 patients with 1176 implants].
AB  - The following study reviews patients from the Department of Oral Surgery and
      Stomatology at the University of Berne undergoing implant therapy. Between 2000
      and 2002, 737 patients received 1176 ITI screw-type implants. At least 70% of
      these patients were 50 years or older. The main reason for tooth loss in this
      group was often periodontitis, followed by carious, periapical infection and root
      fractures. Only 15% of the patients were younger than 30 years. They had lost
      their teeth mainly due to trauma or agenesis of teeth. This study reports a trend
      towards treatment of partially edentulous patients (>90%), with single tooth gaps
      (>50%) being the most frequent indication for implant therapy. The analysis also
      demonstrated the importance of augmentation procedures prior to implant
      placement. Almost 40% of the implant cases required either ridge augmentation or
      sinus lift procedures. The GBR technique was frequently utilized in the anterior
      maxilla, especially with bone defects resulting from dental trauma. Data also
      showed that with these augmentation procedures more implants were inserted in the
      maxilla (53%) than in the mandible. During the healing or early loading phase
      only six implants out of 1176 were lost, resulting in an early failure rate of
      0.51%. Our study has demonstrated that a high level of implant success can be
      achieved with the ITI system when using a strict selection criteria and stringent
      operating protocols.

PMID- 15250176
TI  - [Practice-related diagnostic classification of orofacial pain].
AB  - In this article, a practical diagnostic classification of orofacial pain for use
      in the general dental practice is presented. In contrast to the detailed taxonomy
      proposed by Okeson (1995), this classification is limited to those pain
      conditions dentists are confronted with most frequently. Furthermore, the
      fundamental differences of somatic versus neuropathic pain, localized versus
      widespread pain, and acute versus chronic pain are emphasized. Principles of
      managing the different pain entities are suggested.

PMID- 15250178
TI  - Implicit word activation during pre-recognition processing influences correct
      recognition and estimates of presentation frequency.
AB  - False recognition of new test words is higher for experimental lures (e.g.,
      universal) with initial phonemes identical to studied words (e.g., university)
      than for control lures. A proposed mechanism to explain this phenomenon involves
      implicit activation of potential solution words during the brief period of
      uncertainty immediately following onset of a spoken study word. Two experiments
      examined whether the presumed pre-recognition processing during the stimulus
      discovery phase of spoken word identification increased familiarity of a studied
      word, thereby increasing correct recognitions and estimates of presentation
      frequency. Critical test words were presented a single time during study in
      Experiment 1, and their phonologically related words were presented one, two, or
      three times. Correct recognition and frequency estimates of targets were enhanced
      by multiple presentations of associates sharing initial phonemes. Experiment 2
      provided a replication with five repetitions of phonological associates during
      study and two study presentations of critical test words. The results of these
      two experiments confirmed a necessary theoretical consequence of the implicit
      activation mechanism that has been invoked to explain the effects of phonological
      similarity on false recognition.

PMID- 15250177
TI  - [Necrotizing ulcerative periodontitis. Diagnosis, treatment and follow-up--a case
      report].
AB  - Necrotizing ulcerative gingivitis (NUG) and necrotizing ulcerative Periodontitis
      (NUP) share many clinical and etiologic characteristics. Both forms are
      characterized by necrotic gingival tissues, bleeding and pain. Malodor and
      malaise may be also present. NUG is an infection limited to the gingiva whereas
      NUP also involves the attachment apparatus. Predisposing factors may include
      immune dysfunction, poor oral hygiene, cigarette smoking and emotional stress.
      NUG and NUP might possibly be different stages of the same infection. This case
      report shows the successful treatment of a patient suffering from NUP.

PMID- 15250179
TI  - Extending the revelation effect to faces: haven't we met before?
AB  - The revelation effect is an episodic memory phenomenon where participants are
      more likely to report that they recognise an item when it is judged after an
      interpolated task than when it is not. Although this effect is very robust,
      nearly all of the extant research has used verbal or readily verbalisable
      stimuli. The present two experiments examined whether a revelation effect could
      be produced with non-verbal stimuli such as faces. A revelation effect was found
      in both experiments, for both targets and lures, using faces as stimuli. The
      findings are integrated into the prevailing empirical frameworks for the
      revelation effect and face recognition memory.

PMID- 15250180
TI  - Distinctiveness in flashbulb memory: comparative analysis of five terrorist
      attacks.
AB  - The purpose of the present study was to find out whether a series of terrorist
      attacks, which share some common features, elicit flashbulb memories (of the
      personal circumstances in which the person first learned about these events) that
      are usually elicited by a single, unexpected, surprising, and personally
      important event. A total of 131 participants answered questions regarding details
      of five terrorist attacks that had taken place in Israel during the years 1995
      1997. In addition, they assessed, for each of the five events, the number of
      overt rehearsals, and the degrees of emotional intensity, surprise, novelty,
      personal importance, and distinctiveness. Data analyses showed that most
      variables that are usually associated with the formation of flashbulb memories
      were also found in memories of the terrorist attacks that were judged by the
      participants as being distinctive. Distinctiveness may therefore be considered an
      important factor in the formation of flashbulb memories.

PMID- 15250181
TI  - The effect of midazolam on implicit and explicit memory in category exemplar
      production and category cued recall.
AB  - Transfer-appropriate processing theory (Roediger, Weldon, & Challis, 1989)
      proposes that dissociations between performance on explicit and implicit memory
      tests arise because these tests often rely on different types of information
      processing (e.g., perceptual processing vs conceptual processing). This
      perspective predicts that implicit and explicit memory tasks that rely primarily
      on conceptual processing should show comparable results, not dissociations.
      Numerous studies have demonstrated such similarities. It is, however, possible
      that these results arise from explicit memory contamination of performance on
      implicit memory tasks. To address this issue, an experiment was conducted in
      which participants were administered the sedative midazolam prior to study.
      Midazolam is known to create a temporary, but dense, period of anterograde
      amnesia. The effects of blocking stimulus materials by semantic category at study
      and generation at study were investigated on category exemplar production and
      category-cued recall. The results of this study demonstrated a dissociation of
      the effects of midazolam on category exemplar production and category-cued
      recall. Specifically, midazolam reduced the effect of blocking stimulus materials
      in category-cued recall, but not in category exemplar production. The
      differential effect of midazolam on explicit and implicit memory is at odds with
      transfer-appropriate processing theory and suggests that theories of memory must
      distinguish the roles of different types of conceptual processing on implicit and
      explicit memory tests.

PMID- 15250182
TI  - Dyslexic students have more everyday cognitive lapses.
AB  - There is a dearth of information about the everyday performance difficulties of
      adult dyslexic people. This study investigates the empirical support for
      anecdotal reports of increased vulnerability to distraction in dyslexia, using
      the self-report Cognitive Failures Questionnaire (CFQ). Two groups of university
      students, a dyslexic group and a non-dyslexic control group, were asked to
      complete the CFQ. The dyslexic group reported a higher frequency of everyday
      lapses in cognition, scoring significantly higher on a number of CFQ items.
      Representative problems include distractibility, over-focusing (so that relevant
      peripheral information is missed), and word-finding difficulties. A similar
      measure administered to close friends of dyslexic people, the CFQ-for-others,
      yielded results consistent with those of the CFQ, with major findings being that
      their friends considered them to be more disorganised, more distractible, and
      more absent-minded than normal. The results indicate clearly the continuing
      effects of dyslexia on cognition in adulthood and demonstrate that dyslexic
      impairments are not limited to "artificial" laboratory tasks or even literacy
      tasks but, instead, pervade everyday life.

PMID- 15250183
TI  - Focused attention on one contextual attribute does not reduce source memory for a
      different attribute.
AB  - In three experiments, participants were asked to learn a particular contextual
      dimension of a study episode for a later memory test. The hypothesis being
      evaluated was that focused attention towards learning a particular source
      specifying attribute would decrease memory for a different attribute dimension.
      Although source memory for the attribute dimensions in the focus of attention
      were generally improved, memory was not diminished for contextual attributes
      ostensibly outside the focus of primary attention. The absence of any decrease in
      memory appears to be a somewhat general phenomenon because it was found with
      external-external, internal-external, and internal-internal combinations of
      attribute dimensions. The results may be most consistent with a model of
      cognitive processing in which people have separate pools of attentional resources
      rather than a single pool of general resources.

PMID- 15250184
TI  - Preschoolers' comprehension of goal structure in narratives.
AB  - Preschool children's understanding and use of goals were studied in two
      experiments. Children heard stories in the presence of pictures or props. The
      stories were varied by goal success occurring early or late in the story, with
      late goal success resulting in more causal connections in the narrative. The
      results showed that children recalled goals spontaneously and that their recall
      benefited from goal structure of the stories. Pictures benefited the children
      when the stories were short. Enactment of the props versus static displays of the
      props did not enhance recall in the second experiment. Preschool children thus
      demonstrated ability to infer and use goal and causal information in stories for
      both picture and object support.

PMID- 15250185
TI  - The influence of partial-match cues on event-based prospective memory.
AB  - In event-based prospective memory tasks people form an intention to respond when
      an environmental cue signals that conditions are appropriate to fulfil an
      intended activity. In the ongoing activity the authors embedded partial-match
      cues that only partially, but not completely, satisfied the conditions required
      to make a prospective response. The consequence of encountering these partial
      match cues was to increase responses to appropriate prospective memory cues
      encountered later. This outcome occurred both with semantic and orthographic
      cues, but only the former led to longer processing latencies of the partial-match
      cues. This asymmetry suggests that partial-match cues may not need to be
      processed consciously in order to benefit event-based prospective memory. A
      parametric manipulation of the number of partial-match cues resulted in
      numerically but not statistically better prospective memory. Consequently,
      partial-match cues may function as overt reminders of the intention to respond or
      they may serve to engage participants in self-initiated remindings of the
      intention.

PMID- 15250186
TI  - Memory for emotional stories in high and low depressed children.
AB  - Cognitive theories of depression emphasise a vicious circle linking depressed
      mood and biased recall towards negative information. In line with this, depressed
      adults show selectively enhanced recall for negative information. This recall
      bias is held to be mediated by increased accessibility of negative self-referent
      schemas formed as a result of adverse early experiences. Given this, surprisingly
      few studies have examined depression-related recall biases from a developmental
      perspective. Clinically depressed children have been found to show enhanced
      recall of negative adjectives, particularly when self-referent, but to date there
      is no evidence for similar recall biases in non-clinically depressed groups. The
      current study addressed this by investigating high and low non-clinically
      depressed children's (aged 5-11 years) recall of emotional stories. High
      depressed children showed enhanced recall of negative stories, relative to
      positive stories, compared to the low depressed group. This did not vary with age
      group. We conclude that, when child-oriented materials are used, depression
      related biases in recall towards negative information are observable even in a
      non-clinical sample of children from 5 years of age.

PMID- 15250187
TI  - True and false memory in the absence of perceptual identification.
AB  - Two experiments are reported in which, after attempting to identify a briefly
      flashed, masked test word, participants were asked to rate the likelihood that it
      had been presented in an earlier study list. Even when people were unable to
      identify such items, they demonstrated an ability to discriminate between those
      that were studied and those that were not studied; ratings given to studied items
      were significantly higher than ratings given to nonstudied items. This effect
      does not appear to be a data-driven phenomenon. In Experiment 1 it was found when
      the presentation modality was changed from study to test. In Experiment 2 false
      memory for unidentified items that were related to studied items was shown.

PMID- 15250188
TI  - Arousal, valence, and memory for detail.
AB  - A common finding in the emotion-memory literature is that memory is enhanced for
      positively arousing stimuli and negatively arousing stimuli relative to neutral
      stimuli. We tested the notion that post-stimulus elaboration is responsible for
      these effects. Post-stimulus elaboration refers to the process of thinking about
      an event (after its offset) more frequently or more in-depth. We tested the
      hypothesis by presenting participants with 36 slides depicting events that varied
      in arousal (low and high) and valence (positive and negative). The opportunity
      for elaboration was manipulated by requiring participants, during the interslide
      interval, to complete addition problems, simply view the addition problems, or
      view a blank slide. Cued recall memory was tested for central and background
      details. Based on the post-stimulus elaboration hypothesis it was expected that
      the greatest memory decline would occur for the central details of negatively and
      positively arousing slides when participants were required to complete addition
      problems (i.e., a distractor task x arousal x detail interaction). Contrary to
      the hypothesis, we found that filling the inter-slide interval with a distractor
      task decreased memory for negative stimuli compared to positive stimuli. This
      effect was independent of arousal. We also found that arousal increased central
      detail memory for positive and negative stimuli and background detail memory for
      positive stimuli but not for negative stimuli. This interaction was explained on
      the basis of pre-attentive encoding and cue utilisation. It was concluded that in
      order to understand the complex relationship between emotion and memory, future
      studies should include, as a minimum, the variables of valence, arousal, and
      detail.

PMID- 15250189
TI  - Directed forgetting in working memory: age-related differences.
AB  - This study explored the effects of ageing on working memory by means of the
      directed forgetting procedure designed by Reed (1970). Memory for a letter
      trigram was compared in conditions where it was either presented alone (single
      item), or followed by a second trigram to be recalled (interference), or followed
      by a second trigram to be forgotten (directed forgetting). The results clearly
      indicated that elderly participants inhibited the no-longer-relevant information
      less efficiently (recall in the single-item condition - recall in the directed
      forgetting condition), as predicted by the model of Hasher and Zacks (1988).
      However, the results also demonstrated that sensitivity to interference (recall
      in the single-item condition - recall in the interference condition) increased in
      the condition in which no inhibition was directly required.

PMID- 15250190
TI  - A review of the new Stark Phase II regulations.

PMID- 15250192
TI  - Subdural hematoma. Presentation and management in older adults.
AB  - Subdural hematomas pose diagnostic and therapeutic difficulties in older adults.
      Presenting signs and symptoms of subdural hematomas--headache, confusion, ataxia,
      and hemiparesis--can mimic other diseases such as dementia, stroke, transient
      ischemic attacks, neoplasm, and normal pressure hydrocephalus. Patients with
      subdural hematomas and focal neurologic signs should be considered for surgical
      Intervention, whereas asymptomatic patients or patients with only complaints of a
      headache can be managed medically or followed with serial neuroimaging by
      computed tomography. Patients who have been chronically anticoagulated pose a
      dilemma when they present with a subdural hematoma.

PMID- 15250193
TI  - Diabetes prevention. A GAMEPLAN for success.
AB  - Diabetes prevalence is growing at epidemic proportions, and the greatest increase
      in number of cases is anticipated to be among older adults. The Diabetes
      Prevention Program (DPP) showed that diabetes can be prevented or delayed among
      people with pre-diabetes (impaired glucose tolerance, impaired fasting glucose,
      or both). The National Diabetes Education Program has developed tools adapted
      from the DPP that primary care providers can use to counsel middle-age and older
      patients on diabetes prevention.

PMID- 15250194
TI  - Marked edema of hand with numerous pustules. Patient's line of work as dishwasher
      appears to exacerbate condition.

PMID- 15250196
TI  - [Evaluation of evidence-based medicine].

PMID- 15250195
TI  - Apathy in the older adult. Why you should care.

PMID- 15250197
TI  - [Clinical observation on treatment of acute gouty arthritis by tongfengkang].
AB  - OBJECTIVE: To objectively evaluate the clinical therapeutic effect of
      tongfengkang (TFK) in treating acute gouty arthritis. METHODS: Adopting
      randomized single blinded controlled trial, the 40 patients were equally divided
      into two groups. The tested group was treated with TFK, the control group was
      treated with indomethacin and allopurinol, the therapeutic course for both groups
      was 10 days. RESULTS: The clinical cure rate in the tested group and the control
      group was 30% and 35% respectively, and the total effective rate 90% and 95%
      respectively, with no significant difference between the two groups (P > 0.05).
      The scores of blood uric acid and symptom significantly lowered in both groups
      after treatment (P < 0.01), but showed no significant difference between them (P
      > 0.05). Adverse reaction to the treatment was shown in 3 patients in the control
      group. CONCLUSION: The therapeutic effect of TFK is similar to that of
      indomethacin plus allopurinol but with less adverse reaction, it is an effective
      and safe remedy for treatment of acute gouty arthritis, and worthy for further
      studying and developing.

PMID- 15250198
TI  - [Clinical study on female obesity complicated with climacteric syndrome treated
      by acupuncture].
AB  - OBJECTIVE: To explore the mechanism of acupuncture in treating obesity
      complicated with climacteric syndrome (OCCS). METHODS: Thirty female OCCS
      patients were treated by acupuncture, combination of body and auricular
      acupuncture, according to the treating principle based on syndrome
      differentiation. The changes in symptoms, signs, obesity index, Kupperman index,
      vegetative nerve system equilibrium index (Y value), levels of estradiol (E2),
      luteinizing hormone (LH), follicle stimulating hormone (FSH), gonadotropin
      releasing hormone (GnRH), leptin (LP), insulin (INS), nitric oxide (NO), nitric
      oxide synthase (NOS) and insulin activation index (IAI) in patients were
      observed. RESULTS: The obesity index, Kupperman index, Y value, and levels of LH,
      FSH, GnRH, LP, and INS increased, while levels of E2, NO, NOS and IAI decreased
      in OCCS patients. After acupuncture treatment, in the same time of obtaining
      promising effect in reducing weight, reversing effect was shown in all the above
      mentioned parameters (P < 0.05 or P < 0.01) . CONCLUSION: Acupuncture has
      favorable regulatory effect on Kupperman index, Y value, E2, LH, FSH, GnRH, NO,
      NOS, LP, INS and IAI in OCCS patients, its effect in improving the hypothalamic
      pituitary-gonad axis, vegetative nerve function and vasomotor dysfunction, and
      adjusting the resistance to leptin and insulin may be the important mechanisms.

PMID- 15250199
TI  - [Effect of combined therapy of shenmai and compound danshen injection on
      myocardial reperfusion injury after percutaneous coronary intervention in
      patients with acute myocardial infarction].
AB  - OBJECTIVE: To explore the effect of combined therapy of shenmai and compound
      danshen injection (SM-DS) on myocardial reperfusion injury after percutaneous
      coronary intervention (PCI) in patients with acute myocardial infarction (AMI).
      METHODS: Thirty-eight AMI patients who received PCI were randomly divided into
      two groups, the 19 patients in the treated group were treated with SM-DS before
      and after PCI. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD),
      interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in patients'
      venous blood were measured at different time-points, and the integrated left
      ventricular ejection isometric index (Tei) was determined by echocardiogram.
      RESULTS: As compared with before operation in the treated group, MDA was higher
      and SOD was lower at 2 hrs, 24 hrs after operation (P < 0.05); IL-6 and TNF-alpha
      were significantly lower at 24 hrs, 48 hrs and 1 week (P < 0.05, P < 0.01) and
      the Tei began to be improved at 24 hrs (P < 0.05) and significantly improved at 1
      week after operation (P < 0.01). While in the control group, MDA was higher and
      SOD was obviously lower at 2 hrs and 24 hrs (P < 0.01); lowering of IL-6 and TNF
      alpha appeared at 1 week (P < 0.05) and improving of Tei index revealed 1 week
      after operation respectively (P < 0.05). Comparison between the two groups showed
      significant difference in levels of MDA and SOD at 2 hrs and 24 hrs (P < 0.01);
      significant difference in levels of IL-6, TNF-alpha at 24 hrs, 48 hrs and 1 week;
      and in Tei index at 24 hrs and 1 week after operation (P <0.05). CONCLUSION: SM
      DS could reduce the myocardial reperfusion injury in patients with AMI after PCI.

PMID- 15250200
TI  - [Systematic assessment on randomized controlled trials for treatment of stable
      angina pectoris by compound salvia pellet].
AB  - OBJECTIVE: To assess the therapeutic effect and safety of compound salvia pellet
      (CSP) in treating stable angina pectoris (SAP). METHODS: Literatures regarding
      randomized clinical trials of CSP versus nitrate ester preparation in treating
      SAP, without any language limitation, were reviewed. Jadad scale was used to
      assess the methodological quality of the inclusive trials, and Cochrane
      systematic evaluation was applied for it. RESULTS: Seventeen randomized trials
      conformed to the inclusion criteria were reviewed, all in Chinese language. The
      combined results of the two comparing groups on therapeutic effect in symptom of
      angina and electrocardiogram (ECG) showed that the relative risk (RR) was 1.12
      (1.06, 1.19) and the 95% credibility interval (CI) was 1.42 (1.20, 1.57).
      CONCLUSION: Based on the Cochrane systematic review, CSP showed the therapeutic
      effect in treating SAP on relieving angina and improving ECG better than that of
      nitrate ester preparation, and with less adverse reaction and good tolerance.
      However the conclusion cannot be reached yet due to the low methodological
      quality of the trials collecting and lacking in some important final markers and
      relevant criteria for quality of life, more rationally designed and strictly
      executed randomized trials with large samples are necessary.

PMID- 15250201
TI  - [Preventive effect and clinical significance of garlicin injection on mechanical
      ventilator-associated low respiratory tract deep-seated fungal infection].
AB  - OBJECTIVE: To investigate the preventive effect and clinical significance of
      garlicin injection on ventilator-associated low respiratory tract deep-seated
      fungal infection (VRFI) as pneumonia. METHODS: Retrospectively analysis on 147
      patients underwent mechanical ventilation in our Intensive Care Unit (ICU) in
      recently 3 years was conducted. According to the garlicin injection
      administration was used or not, 79 patients with WVUH (West Virgina University
      Hospital) score > or = 25 points were selected and divided into the preventive
      group and the control group, and the differences in baseline conditions,
      incidence of VRFI and hospital outcome between the two groups were compared.
      RESULTS: There was no significant difference between the two groups in baseline
      data as age, sex, APACHE II score, SAPS II score and WVUH score. But the
      incidence of VRFI in the preventive group was significantly lower than that in
      the control group (P<0.01). The relative risk in the latter was 2.06 (95% CI,
      1.25-3.38). No significant difference was found between the two groups in
      hospital mortality (P>0.05). CONCLUSION: Garlicin injection can effectively
      reduce the incidence of VRFI, and is inexpensive, it is an ideal prophylactic
      anti-fungal drug.

PMID- 15250202
TI  - [Regulatory effect of zengmian mixture on T-lymphocyte dysfunction in children
      with repeated lower respiratory tract infection of both Qi-Yin deficiency type].
AB  - OBJECTIVE: To explore the T-lymphocyte dysfunction in children with repeated
      infection of lower respiratory tract of both Qi-Yin deficiency type (RIR-QYD) and
      the immune regulatory effect of zengmian mixture (ZMM), to provide theoretical
      basis for the effective therapy. METHODS: Peripheral T-lymphocyte subsets and
      expressions of T-lymphocyte activating related surface molecules (CD3+/HLA-DR+
      and CD3+/CD25+, etc.) in children with RIR-QYD, 31 of mild type and 28 of severe
      type cases, were investigated before administration of ZMM and after treatment of
      ZMM for 3-6 months (non-infectious stage), using immune fluorescent labelling and
      flow cytometric technique. RESULTS: In the patients with mild RIR-QYD, the
      expression rate of CD4+ and CD3+/HLA-DR+ activated T-cells before treatment were
      all obviously lowered, after 3 months treatment, the positive rate of CD4+,
      CD3+/HLA-DR- resting T-cell, CD3+/HLA-DR+ activated T-cell and CD3+/CD25+ express
      IL-2R T-cells were all obviously lowered, but after treatment for 6 months, only
      that of CD3+/HLA-DR+ activated T-cells was lower than that in the control group.
      In the patients with severe RRI-QYD before treatment, the expression rate of
      CD3+, CD4+, CD3+/HLA-DR-, CD3+/HLA-DR+ and CD3+/CD25+ all lowered, while after 3
      6 months treatment, some recoveries were shown in these parameters but still
      lower than those in the control group. The total effective rate of ZMM for mild
      patients was 100%, and the markedly effective rate 78.9%, while for severe cases,
      the total effective rate was 90.9% and the markedly effective rate 68.2%.
      CONCLUSION: In patients with RIR-QYD, the T-cells decreased with activating
      dysfunction, the severity of disease is in accordance with the degree of T-cell
      activating dysfunction. ZMM shows markedly clinical effect in treating RIR-QYD
      and evident regulatory effect on T-cell dysfunction, but a long-term treatment is
      needed for the recovery of laboratory parameters.

PMID- 15250203
TI  - [Clinical study on effect of chuankezhi injection in treating children with
      bronchial asthma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of chuankezhi injection to
      children with bronchial asthma. METHODS: Sixty-eight children suffered from
      asthma and/or asthma complicated with allergic rhinitis were randomly divided
      into the treated group and the control group, who received treatment of
      chuankezhi injection and Ginkgo injection respectively. Clinical observation on
      daily-symptom scores, and lung functions as peak expiratory flow (PEF), and
      forced expiratory volume in one second (FEV1) were conducted. RESULTS: After
      treatment the median of symptomatic scores in the treated group was 6.0 (M25-M75:
      4.9-21.5) and that in the control group was 10.0 (M25-M75: 6.19-27.5), showing
      significant difference between groups; significant improvement was shown in the
      treated group, in which the PEF variance rate was reduced to 4.3 +/- 5.1%, while
      in the control group, it was 5.9 +/- 6.7%, the difference between the two groups
      was significant. Similar result also showed in comparison of FEV1 rate.
      CONCLUSION: Chuankezhi is helpful in improving clinical symptoms, reducing PEF
      variance rate and enhancing lung function in children with bronchial asthma, so
      as to be benefit to the long-term stable alleviation of asthma.

PMID- 15250204
TI  - [Effect of integrative Chinese and western medicine on T-lymphocyte subsets in
      treating patients with severe acute respiratory syndrome].
AB  - OBJECTIVE: To investigate the therapeutic effect of integrative Chinese and
      western medicine (ICWM) in treating severe acute respiratory syndrome (SARS) and
      its influence on T-lymphocyte subsets. METHODS: Comparative study was conducted
      in 133 SARS inpatients in Beijing Ditan Hospital, who were divided into 3 groups
      according to the treatment applied, the basic treated group, the low dose steroid
      group and the high dose steroid group, and all the 3 groups were subdivided into
      two groups, Chinese herbs and non-Chinese herbs added, respectively. Chinese
      drugs for clearing-up heat, dispelling dampness, detoxication, removing stasis,
      supplementing Qi and nourishing Yin were selected according to patients' syndrome
      and given additionally to all the three ICWM groups. Retrospective analysis for
      significance test on changes of T-lymphocyte subsets before and after treatment
      were carried out. RESULTS: T-lymphocyte counts, including CD3+, CD4+, CD8+,
      lowered in all patients before treatment, but increased significantly after
      treated for 3 weeks, the increment in all the low dose steroid treated groups was
      higher than that in the basic treated groups, and that in ICWM groups was higher
      than that in non-ICWM groups, respectively. CONCLUSION: Glycocorticosteroid and
      Chinese herbal medicine treatments could promote the recovery of T-lymphocyte
      profile, rationally use of them is the effective therapeutic method.

PMID- 15250205
TI  - [Investigation and analysis on diagnostic standard for TCM Syndrome
      Differentiation in 400 patients with climacteric syndrome].
AB  - OBJECTIVE: To explore the thinking and method of studying the diagnostic standard
      for TCM Syndrome Differentiation by means of clinical epidemiological
      investigation on climacteric syndrome. METHODS: Adopting DME (design measurement
      evaluation), the field investigation data of 400 patients with climacteric
      syndrome were statistically managed and analyzed using blind method. The
      distribution of syndromes, including information of four-diagnosis of various
      syndromes as well as the laboratory findings in patients were studied using
      factor analysis and model of structural equation. RESULTS: The Syndrome types of
      climacteric syndrome were identified as the Gan-Yang exuberance type, the Shen
      Yang deficiency type, the Gan-Shen Yin-deficiency type and the Gan-stagnancy
      injuring Spirit type. CONCLUSION: Thinking of the diagnostic standard study for
      TCM Syndrome Differentiation is to identify the supposed diagnostic standard of a
      disease based on retrospective study, to formulate a new hypothetical standard of
      Syndrome by way of field investigation, category analysis, factor analysis, and
      critical theory, followed with identification of Syndrome distribution in the
      disease, its critical syndrome, typical syndrome, complicated syndrome, and
      criteria for Syndrome Differentiation.

PMID- 15250206
TI  - [Effect of magnesium lithospermate B on endothelial cells in human aorta after
      free radical injury].
AB  - OBJECTIVE: To study the cardiovascular effects of magnesium lithospermate B
      (MLB), a water soluble extract from red sage root, on human aortic endothelial
      cells (HAECs) proliferation and in treating free radical injured endothelial
      cells, so as to further understand the cardiovascular pharmacological mechanism
      of MLB. METHODS: HAECs of 3-6 passages were used in the experiment. MLB of
      different concentrations was used to treat the cells, and cell proliferation was
      observed using morphological and MTT method. The free radical injured model cell
      was made by glucose-glucose oxidase method for observing the effect of MLB on its
      microstructure by transmission electron microscopy. RESULTS: MLB in concentration
      of 1.0 mg/ml and 0.5 mg/ml had significant cytotoxicity (P<0.01), when its
      concentration was lower than 0.2 mg/ml, the drug showed no adverse reaction on
      cell proliferation. MLB showed significantly cell protective effect against free
      radical injury, the effect in protecting ultrastructure of cells, such as
      mitochondria, could be demonstrated in transmission electron microscopy.
      CONCLUSION: MLB showed a low cytotoxicity on HAECs, it could obviously protect
      cells from free radical injury.

PMID- 15250207
TI  - [Effect of bushen yiqi recipe on bioactivity behavior of human cytotrophoblast of
      early pregnancy].
AB  - OBJECTIVE: To investigate the effect of Chinese drugs for tonifying Shen on the
      bioactivity, cell proliferation, invasion and differentiation of human
      cytotrophoblast of early pregnancy. METHODS: The human early pregnant
      cytotrophoblast was cultured in vitro, and treated with saline (as blank control)
      and drug containing serum in different concentrations (5%, 10% and 20%)
      respectively. The changes of morphology, proliferation and invasive capacity of
      cells were examined by scanning electron microscopy, MTT method, flow cytometry,
      Transwell invasive assay at 24 hrs, 48 hrs and 72 hrs after treatment. RESULTS:
      After cells being cultured with drug containing serum, the cytotrophoblast became
      abundant in microvilli, with more and prolonged pseudopodia. The cell absorbency
      in 490 nm wave length increased significantly (P < 0.01), cells of sub-G1 and
      G2/M phase obviously decreased and that of S phase increased (P < 0.01), and the
      cells penetrated through PET membrane in each visual field significantly
      increased (P < 0.01). CONCLUSION: Chinese herbs for tonifying Shen could promote
      the proliferation and invasive capacity of cytotrophoblast and might influence
      its differentiation.

PMID- 15250208
TI  - [Effect of heart benefiting recipe in controlling IL-1beta, IL-6 and APPmRNA
      expression in brain of beta-amyloid protein induced rat model of dementia].
AB  - OBJECTIVE: To investigate the neuro-immune regulatory mechanism of Heart
      Benefiting recipe (HBR), an effective recipe for treatment of Alzheimer's disease
      (AD). METHODS: Using immunohistochemical and RT-PCR methods, the neuro
      immunological pathological changes in the AD rat model induced by beta-amyloid
      protein (A beta1-40) via lateral cerebral ventricle injection, including mainly
      the glial fibrillary acidic protein expression and inflammatory cytokines IL
      1beta, IL-6mRNA and beta-amyloid protein precursor (APPmRNA) gene expression were
      studied. And the effects of HBR on these parameters were observed. RESULTS:
      Deposition of A beta in cerebral tissue could induce activation of stellate glial
      cells and abnormal increased levels of inflammatory cytokines (IL-1beta and IL
      6mRNA), also the elevation of APPmRNA level. HBR could effectively control the
      above-mentioned pathological changes. CONCLUSION: HBR could effectively control
      the inflammation and the A beta immune cascade reaction in brain of AD patients,
      it is one of the important therapeutic mechanisms of the recipe.

PMID- 15250209
TI  - [Effect of xiaoke granule on blood glucose, urinary protein and glomerular
      morphology in rats with diabetic nephropathy].
AB  - OBJECTIVE: To observe the changes of blood glucose, urinary protein and renal
      glomerular morphology in rats with diabetic nephropathy, and the effect of xiaoke
      granule (XKG) on them. METHODS: The diabetic nephropathy model was established by
      3/4 nephrectomy and once intraperitoneal injection of streptozotocin (STZ). The
      experimental rats were divided into the model group, the XKG group, the positive
      control group and the sham operation group. Blood was taken from rat's caudal
      vein to test the fasting blood glucose (FBG) once every week after STZ injection
      and at the same time, urinary protein in 24 hrs (UP/24h) was investigated. All
      the rats were sacrificed 2, 6 weeks after STZ injection and morphological
      examination on their kidney was performed. RESULTS: Six weeks after STZ
      injection, glomerular sclerosis in various degrees was seen in the model group,
      but the pathological change was significantly milder in the treated groups. FBG
      in the model group was higher than that in the sham operation group at all time
      points respectively (P<0.05), while in the XKG group and the positive control
      group, the change was improved significantly. UP/24h in the model group was
      higher than that in the sham operation group at all time points respectively, and
      that in the XKG group at 1, 2 and 3 weeks after STZ injection was significantly
      lower than that in the model group. FBG and UP/24h showed a positive correlation.
      CONCLUSION: A rat model of diabetic nephropathy was duplicated successfully. The
      elevated blood glucose level in diabetic nephropathy model could induce
      proteinuria. One of the routes of treatment of diabetic nephropathy by XKG is to
      reduce the blood glucose, eliminate the proteinuria, and thus to improve the
      pathological change in renal glomeruli.

PMID- 15250210
TI  - [Experimental study on preventive effect of Radix Paeoniae Rubra to restenosis
      after carotid balloon injury in high fat-diet rabbits].
AB  - OBJECTIVE: To observe the preventive effect of Radix Paeoniae Rubra (RPR) to
      restenosis after carotid balloon injury in rabbits. METHODS: The rabbit model of
      carotid balloon injury was established adopting Clowes method, and treated with
      extract of RPR. Component of new genesic intima and expression of proliferating
      cell nuclear antigen (PCNA) and macrophage was determined by immunochemical
      stain. The collagen of type I was detected by special staining for blood vessels
      and the area of new genesic intima was measured by image assay system. RESULTS:
      RPR could remarkably decreased the PCNA positive expression and inhibit the
      proliferation of collagen type I and reduce the generating of new intima.
      CONCLUSION: RPR has significant preventive effect on the restenosis after carotid
      ballon injury in high fat-diet induced atherosclerotic rabbits.

PMID- 15250211
TI  - [The protective effect of shenfu injection on myocardium against ischemia
      reperfusion injury in rats].
AB  - OBJECTIVE: To observe the protective effect of Panax Ginseng (PG), Aconitum
      Carmichaeli (AC), and their combination (PG-AC) on myocardial
      ischemia/reperfusion injury in rats. METHODS: Rat's ischemia reperfusion injury
      model was established by ligating left anterior descending coronary artery for 60
      min followed by reperfusion for 240 min. Forty male rats were randomly divided
      into five groups, the sham operation group, the model group, the three treated
      groups. The three treated groups were treated with PG, AC and PG-AC respectively
      by given the drugs 10 min before ischemia reperfusion, and to the sham operation
      group and the model group, saline was given instead. The infarction area,
      pathologic changes of myocardial tissue (under light and electron microscopy),
      activity of creatine phosphokinase (CK) and lactate dehydrogenase (LDH) in serum,
      content of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardial
      tissue were observed to evaluate the protective effect of treatment. RESULTS: The
      area of acute myocardial infarction was lesser, activity of LDH and CK were lower
      in the three treated groups than those in the model group. Content of SOD was
      significantly higher and that of MDA was markedly lower in the former three than
      those in the model group. Light and electron microscopic examination showed that
      the necrotic degeneration and pathologic changes of myocardiocytes in the treated
      groups were significantly milder than that of the model group. As comparing the
      effect between the three treated groups, PG-AC showed the best, and insignificant
      difference was shown between PG and AC. CONCLUSION: Both PG and AC, and their
      combination have obviously protective effects on myocardium against ischemia
      reperfusion injury, which of PG-AC is superior to that of PG or AC used singly.

PMID- 15250212
TI  - [Experimental study on regulatory effect of compound gengniankang on endocrine
      and immune functions in aged female rats with osteoporosis].
AB  - OBJECTIVE: To observe the effect of compound gengniankang (GNK) in regulating the
      endocrine and immune functions in aged female rats. METHODS: Aged female rats
      with osteoporosis were selected as the object for observation and healthy young
      rats were taken for control. Animals were administered by GNK and nilestriol
      respectively, through gastric perfusion, for 3 months to observe the therapeutic
      effect of drug treatment on osteoporosis and the regulatory effect on endocrine
      and immune function. Bone mineral density (BMD) was measured by double energy X
      ray absorption technique, serum levels of estradiol (E2), follicule-stimulating
      hormone (FSH) and luteinizing hormone (LH) were determined by RIA, T-cell subsets
      and apoptosis in spleen were detected by flow cytometry. RESULTS: In aged rats
      with osteoporosis, the BMD decreased, serum level of E2 lowered, FSH and LH
      levels raised, splenic CD4+, CD4+/CD8+ significantly decreased and T-cell
      apoptosis rate significantly elevated. GNK could increase the BMD, lower the FSH
      and LH levels, but showed no significant effect on E2 level. It could increase
      the CD4+ and CD4+/CD8+ ratio to nearby the normal range, and reduce the apoptosis
      of T-cells. CONCLUSION: GNK has therapeutic effect on osteoporosis in aged rats,
      and is able to regulate the endocrine and enhance the immune function in
      organism.

PMID- 15250213
TI  - [Study on the effect of weitongning on epidermal growth factor and nitric oxide
      contents in tissue of stomach of rats with gastric ulcer].
AB  - OBJECTIVE: To study the therapeutic mechanism of weitongning (WTN) in treating
      peptic ulcer. METHODS: Rat model of chronic gastric ulcer induced by glacial
      acetic acid was used to observe the effect of WTN on the curative quality,
      thickness of regenerated mucous membrane, epidermal growth factor (EGF) and
      nitric oxide (NO) contents in scar tissue around the gastric ulcer. RESULTS: The
      thickness of regenerated mucous membrane, EGF and NO contents in peri-ulcer scar
      tissue were higher in the model rats after WTN treatment than that in the
      untreated model rats (P<0.01 or P<0.05). CONCLUSION: WTN could elevate the
      quality of ulcer curing, to raise the EGF and NO contents in peri-ulcer scar
      tissue might be one of its mechanisms for preventing relapse of peptic ulcer.

PMID- 15250214
TI  - [Clinical observation on treatment of infantile repeated respiratory infection by
      combined use of heluo oral liquid and Astragalus].

PMID- 15250215
TI  - [Clinical study on treatment of primary hypertension by niuhuang jiangya pill].

PMID- 15250216
TI  - [Clinical study on treatment of chronic obstructive pulmonary disease in stable
      stage by bufei yishen recipe].

PMID- 15250217
TI  - [Clinical study on 266 patients with chronic renal failure treated by shenshuai
      paidu powder].

PMID- 15250218
TI  - [Clinical effect of acute cerebral infarction treated by ginkgo damo injection
      and it's influence on SOD, MDA and NO].

PMID- 15250219
TI  - [Effect of yiqi huoxue tongluo herbs on circulatory endothelial cells in patients
      with unstable angina pectoris].

PMID- 15250220
TI  - [Study on the pathogenesis mechanism of diabetic neuropathy and intervention on
      it by Chinese and Western medicine].

PMID- 15250221
TI  - [Exploration on the possible mechanism of Chinese drug intervention on ventricle
      remodelling].

PMID- 15250222
TI  - Simple aspiration versus chest-tube insertion in the management of primary
      spontaneous pneumothorax: a systematic review.
AB  - BACKGROUND: The initial treatment of a primary spontaneous pneumothorax (PSP) is
      controversial. Guidelines of the British Thoracic Society recommend simple
      aspiration for all PSP requiring intervention. The placement of chest tubes is
      only advocated for patients who fail simple aspiration. However, the American
      College of Chest Physicians Delphi Consensus Statement found simple aspiration to
      be rarely appropriate in the management of PSP. AIMS: To compare simple
      aspiration with chest-tube drainage in the initial management of PSP. METHODS:
      Meta-analysis of randomized controlled trials (RCTs). OUTCOME MEASURES:
      Reductions in duration of hospital stay, recurrence rate and pain or dyspnoea
      score were classified as benefits, whereas reductions in successful events were
      classified as risks. DATA COLLECTION AND ANALYSIS: For dichotomous data, the
      relative risk (RR) and 95% confidence intervals were calculated. For continuous
      data, weighted mean differences (WMD) were used. RESULTS: Three RCTs were
      identified with a combined total of 194 patients. Simple aspiration was
      associated with shorter hospitalization (WMD -1.30 days [-2.20 to -0.39]). The
      results for success rate could not be combined because of differences in outcome
      definitions. However, a pooled result for "success at 1 week or more" showed no
      significant difference between either intervention (RR 0.86 [0.67, 1.11]).
      Results of recurrence at 1 year were also not significantly different (RR 0.73
      [0.39-1.38]). Different reporting systems for pain scores meant that data could
      not be pooled. Only one trial reported dyspnoea scores. CONCLUSION: RCT evidence
      in this field is limited, and the total sample size is too small to make any firm
      conclusion. On the basis of current available evidence, simple aspiration is
      advantageous in the initial management of PSP because of shorter hospitalization.
      There is no significant difference in recurrence at 1 year using either modality,
      and the efficacy data are inconclusive.

PMID- 15250223
TI  - Clinical application of a simple questionnaire for the differentiation of asthma
      and chronic obstructive pulmonary disease.
AB  - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are highly
      prevalent chronic diseases characterized by airflow limitation. Both diseases
      have a distinct pathogenesis and require unique treatment approaches. Due to some
      common characteristic traits, asthma and COPD are often lumped together in
      clinical practice. We sought to develop a simple questionnaire for the
      distinction of asthma and COPD. METHODS: Clinical discriminants of asthma and
      COPD were retrospectively identified by multiple logistic regression using files
      from 547 consecutive adult patients presenting to a pulmonary specialist practice
      with a diagnosis of asthma or COPD. With these features, we generated a simple
      quantitative questionnaire supporting a diagnosis of COPD with high scores and
      asthma with low scores (range 0-15 points). Questionnaire results were compared
      with physician's diagnosis based on GINA and GOLD guidelines including skin
      tests, spirometry and reversibility data. RESULTS: 210 patients had COPD and 337
      had asthma. Age of onset, smoking history, atopy status, and cough quality were
      significantly associated with a diagnosis of asthma or COPD. Questionnaire scores
      for COPD patients were higher than those for asthmatics (mean score 10.5+/-0.18
      vs. 4+/-0.12, P<0.0001). Receiver operational characteristics (ROC) analysis
      revealed a cutoff score of 7 with the highest discriminant power (87.6%
      sensitivity, 87.2% specificity for COPD, 87.4% correctly classified, area under
      the ROC curve: 0.954). The overlap between asthma and COPD (score 6-8) comprised
      about 20% of the total population, these patients included a higher proportion of
      COPD patients with atopy, and smoking asthmatics. CONCLUSIONS: In patients with
      obstructive airway diseases, a simple questionnaire can support the
      differentiation of asthma and COPD in everyday clinical practice. Further
      prospective trials are necessary to confirm these initial observations.

PMID- 15250224
TI  - Pulmonary function tests in preoperative pulmonary evaluation.
AB  - Pulmonary function testing (PFT) has been used to evaluate the risk for
      postoperative complications since the 1950s. PFT including spirometry, lung
      volumes, diffusing capacity, oximetry, and arterial blood gases has been used to
      assess the postoperative risk of lung resection. In selected cases, additional
      evaluation may include radionuclide lung scanning, exercise testing, invasive
      pulmonary hemodynamic measurements, and risk stratification analysis. A new
      index, predicted postoperative product (PPP), was found to have strong predictive
      ability for mortality. We defined a new useful index, measured product (MP), to
      predict postoperative complications; MP had similar advantages of PPP. Since
      diffusing capacity at rest has been shown to be a good predictor of postoperative
      complications following lung resection, and since exercise testing has been also
      useful in preoperative evaluation prior to lung resection, we reasoned that
      evaluation of the effect of exercise on diffusing capacity would be helpful to
      evaluate the ability of the pulmonary capillary bed to expand and increase its
      capacity to transfer gas during exercise.

PMID- 15250225
TI  - Novel bronchofiberscopic catheter spray device allows effective anesthetic spray
      and sputum suctioning.
AB  - STUDY OBJECTIVES: To evaluate how serum lidocaine concentrations (SLC) rise when
      lidocaine is administered by a Bronchofiberscopic Catheter Spray Device (BCSD),
      and to demonstrate the effect on the aspiration speed of a substitute for sputum
      when a catheter spray remains in the channel of the bronchofiberscope (BF).
      METHODS: This is a prospective randomized clinical study. After lidocaine
      ultrasonic nebulizer, the BF was inserted orally. During the procedure patients
      received 4% lidocaine by two methods. In Group 1, 11 patients received lidocaine
      by bronchofiberscopic (BF) injection. In Group 2, 15 patients received lidocaine
      by spraying from the diameter 1.06 mm catheter through the BF channel. SLC were
      measured at 40 min from onset of nebulization. Separately, we examined how
      effectively sputum was aspirated through the BF channel with a catheter. RESULTS:
      Total lidocaine dose (TLD) is the total dose used for nebulization and for the BF
      injection or spray. The TLD for Groups 1 and 2 were 698.2+/-162.1 mg (mean+/-SD)
      and 498.7+/-103.8 mg, respectively (P = 0.03). The SLC for Groups 1 and 2 were
      1.28+/-0.72 and 1.48+/-0.70 mg/l, respectively (P = 0.49). CONCLUSIONS: Using
      BCSD allows easier in administration of lidocaine and is not associated with a
      significant increase in SLC in comparison with BF injection. Although sputum
      aspiration using the BF inserted with our catheter was somewhat slow, we did not
      feel inconvenient so much. Compared to the conventional method, using BCSD may be
      preferable for patients and bronchoscopists.

PMID- 15250226
TI  - Is birth weight related to lung function and asthma symptoms in Nordic-Baltic
      adults?
AB  - Studies of birth characteristics and respiratory outcomes show contradictory
      findings. We wanted to investigate the association of birth weight with adult
      lung function as well as asthma symptoms while addressing the influence of
      demographic and environmental factors. Data was collected from the birth records
      of 1683 men and women born in 1947-1973 who were included in 6 Nordic-Baltic
      population samples investigated within the European Community Respiratory Health
      Survey (ECRHS). In the adults, an increase in birth weight from below 2500 g to
      above 4000 g was associated with an increase from 96% to 104% predicted one
      second forced expiratory volume (P<0.01) and from 1.00% to 107% predicted forced
      vital capacity (P<0.01). However, birth weight was not associated with symptoms
      of asthma. After adjustment for birth length, gender, age, study centre, adult
      BMI, allergic rhinitis, parental and adult tobacco smoke exposure in multivariate
      regression analyses, birth weight was not associated with adult lung function or
      asthma symptoms. Further sub-sample analyses revealed no influence of gestational
      age, gender, age or geographical area. In this historic prospective cohort study
      an association was neither found between birth weight and adult lung function nor
      between birth weight and asthma symptoms.

PMID- 15250227
TI  - Comparison of conventional nighttime with automatic or manual daytime CPAP
      titration in unselected sleep apnea patients: study of the usefulness of daytime
      titration studies.
AB  - Daytime CPAP titration studies with full polysomnography have been successfully
      performed in patients with severe sleep apnea-hypopnea syndrome (SAHS). The
      implementation of daytime studies in unselected SAHS patients could help to
      reduce the waiting lists for CPAP titrations. The main purpose of this study was
      to compare the effectiveness of conventional versus manual or automatic daytime
      CPAP titration in unselected patients with SAHS. Ninety-three consecutive
      patients with SAHS in whom CPAP was indicated were assigned to conventional
      titration or to manual or automatic (AutoSet) daytime CPAP titration, after sleep
      deprivation. The number of valid studies, sleep architecture, final pressure
      selected and mean pressure in the different sleep stages were compared. Changes
      in sleepiness (Epworth sleepiness score) and hours of CPAP use were assessed
      after 3 months of treatment. Four patients did not sleep (3 AutoSet, 1
      conventional daytime groups). Sleep latency was shorter during automatic daytime
      titration whereas REM latency was shorter in daytime studies; the percentage of
      sleep stages was similar during all types of titration. CPAP requirements were
      significantly higher during REM sleep in conventional and manual daytime
      titrations while mean pressure was unchanged throughout sleep stages during
      AutoSet titration. CPAP pressure selected with conventional or daytime manual
      titration (7.5(2.2) cm H2O and 7.4(1.5) cm H2O, ns) were significantly lower (P<
      0.001) than with AutoSet (9.4(1.6) cm H20. All groups showed similar decrease of
      sleepiness and hours of use of CPAP at 3 months of follow-up. Automatic and
      manual daytime PSG studies after sleep deprivation are useful for CPAP titration
      in unselected patients with SAHS. Pressure selected with AutoSet is significantly
      higher than with conventional daytime or nighttime titration, although not
      significant in terms of treatment compliance and symptom improvement.

PMID- 15250228
TI  - Self-evaluations of tuberculosis patients about their illnesses at Ankara Ataturk
      Sanatorium Training and Research Hospital, Turkey.
AB  - Tuberculosis (TB) is one of the leading causes of morbidity and mortality and
      almost one-third of the world is infected with this disease. In Turkey, it
      remains an important public health concern. In many of the studies, social
      aspects of TB are underestimated. In this study, self-evaluations of TB
      inpatients between the ages of 18 and 65 were assessed between July 29 and August
      01, 2002 at Ankara Ataturk Sanatorium Training and Research Hospital, which is
      one of the major reference hospitals for TB in Turkey. This was a cross-sectional
      epidemiological study in which the participation rate was 88.2%. Mean age of the
      total 97 participants was 41.3 (SD = 13.6) and 80.4% of patients were male.
      Patients expressed "unhappiness and stress (23.7%)" to be the major cause of
      their illness. From the patients' point of view, the three major difficulties
      incorporated in their lives due to TB were "financial problems (27.9%)",
      "loneliness (9.3%)", and "hospitalization (9.3%)". Relationships between the
      patients and their social environments were also assessed in five categories:
      "closest friend at work, closest friend in life, parents, children, and spouse".

PMID- 15250229
TI  - The prognostic significance of vascular endothelial growth factor levels in sera
      of non-small cell lung cancer patients.
AB  - BACKGROUND: Angiogenesis, the formation of new blood vessels from the existing
      vascular bed, is essential step for the growth and invasion of the primary tumor.
      Vascular endothelial growth factor (VEGF) is known to play crucial role in tumor
      angiogenesis. Increased serum VEGF levels may be associated with poor prognosis
      in patients with non-small cell lung cancer (NSCLC). METHODOLOGY: In the present
      study, we measured plasma VEGF levels in 20 normal subjects and 75 patients with
      untreated NSCLC; 23 operable (stages I, II, IIIA) and 52 inoperable (stages IIIB,
      IV) (Histology: squamous cell carcinoma, 40; adenocarcinoma, 27; undetermined,
      8). VEGF was measured by enzyme-linked immunosorbent assay. RESULTS: The median
      VEGF level in patient group was 119 pg/ml (29-1235), which was significantly
      higher than the control group (P = 0.044). Median survival of patients was 210
      days (30-220). The patients were divided into high VEGF (> 119 pg/ml) and low
      VEGF (< 119 pg/ml) groups using the median value as a cut-off. It was
      investigated if there were significant associations between serum VEGF level and
      clinico-pathological parameters like age, sex, histopathological diagnosis and
      TNM staging. Also high VEGF and low VEGF patient groups were compared according
      to the median survival. CONCLUSIONS: Serum VEGF level is significantly associated
      with the clinical staging of the patients (operable and inoperable) (P = 0.031)
      and it also correlates with the prognosis of the patients (P = 0.0006).

PMID- 15250230
TI  - Factors affecting SP-A-mediated phagocytosis in human monocytic cell lines.
AB  - Surfactant protein-A enhances the phagocytosis and killing of many pathogens,
      although studying this effect in an assortment of models and different
      experimental protocols has sometimes yielded conflicting results. In this report,
      using the human THP-1 cell line as the primary phagocytic cell, we systematically
      examined several models where microspheres, Staphylococcus aureus and Escherichia
      coli were used for targets. We found that SP-A derived from human lavage appeared
      to enhance phagocytosis by two different mechanisms; by SP-A binding of the
      target to enhance its recognition and subsequent phagocytosis and by a direct SP
      A stimulatory effect on the phagocyte itself. Both SP-A mechanisms occurred with
      different targets in the same experimental system and the SP-A effects were
      qualitatively (but not quantitatively) comparable in several human cell lines
      (THP-1, U937, Mono-Mac-6). We also found that the SP-A effects were abrogated
      when SP-A was combined with surfactant lipids, but the lipids did not affect the
      basal level of phagocytosis or phagocytosis by mechanisms not involving SP-A.
      Moreover, the stimulatory effect of SP-A was pH-dependent and appeared to be
      independent of several other phagocytic mechanisms, including those mediated by
      Fc receptors and mannose receptor.

PMID- 15250231
TI  - Adenosine 5'-monophosphate increases levels of leukotrienes in breath condensate
      in asthma.
AB  - Hyperresponsiveness (AHR) is a key physiological abnormality in asthma. In
      clinical and research studies AHR is measured bronchial challenge, with
      methacholine (MCh), but more recently with adenosine-5'-monophosphate (AMP). In
      the search for markers of airway inflammation in asthmatic patients, we measured
      the concentrations of histamine and cysteinyl-leukotrienes (cys-LTs) before and
      after MCh and AMP challenges in the exhaled breath condensate of 13 patients with
      mild asthma (FEV1 78.5%pred) and nine healthy non-smokers, using specific enzyme
      immunoassays. With methacholine challenge we did not find any differences between
      asthmatics and normal subjects in the pre- and post-challenge concentrations of
      cys-LTs: 27.2+/-1.4 vs. 29.2+/-1.2 pg/ml and 26.3+/-2.2 vs. 27.5+/-4.2 pg/ml,
      respectively or histamine: 5.1+/-0.4 vs. 5.1+/-0.6 nM and 4.5+/-0.4 vs. 4.4+/-0.3
      nM; P>0.05). In asthmatic patients cys-LT levels were significantly higher after
      AMP challenge (56.2+/-9.7 vs. 31.7+/-6.9 pg/ml; P<0.05); but there was no
      difference in healthy subjects (27.2+/-4.6 vs. 30.3+/-4.7 pg/ml). There was no
      difference in histamine concentrations in asthmatic (5.9+/-1.8 vs. 4.5+/-0.5 nM),
      or healthy subjects (5.5+/-0.4 vs.5.7+/-0.9 nM) after AMP challenge. In
      conclusion, our results show that the cys-LTs are increased in exhaled breath
      condensate after AMP challenge, which may indicate that the AMP acts indirectly
      by releasing cys-LTs from primed mast cells. The detection of LTs and histamine
      in exhaled breath condensate may be useful in monitoring asthma.

PMID- 15250232
TI  - Effect of exercise mode on oxygen uptake and blood gases in COPD patients.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are characterised by
      decreased exercise tolerance, and, more variably, exercise induced hypoxaemia
      (EIH). Evaluation of physical work capacity and physiological responses to
      exercise may be performed by various procedures, but there are diverging opinions
      as to which exercise test should be preferred. In the current study, oxygen
      uptake and arterial blood gases in COPD patients have been compared during
      submaximal and maximal exercise on treadmill and ergometer bicycle. Treadmill
      exercise resulted in higher peak oxygen uptake than bicycle exercise (1111+/-235
      vs. 987+/-167 ml min(-1), P<0.02), while the plasma lactate levels were higher
      during cycling (1.8+/-0.8 vs. 3.8+/-1.7 mmol l(-1), P<0.001). Neither carbon
      dioxide output, ventilation, nor rate of perceived exertion (Borg RPE scale)
      showed significant differences between the two modes of exercise. The EIH during
      both maximal (delta Sa,O2 = -5.6+/-4.2 vs. -3.4+/-5.1%) and sub-maximal exercise
      was more pronounced during treadmill walking than during cycling. The present
      study indicates that the VO2peak in COPD patients is higher, the maximal lactate
      concentrations lower and the development of EIH more pronounced when exercise
      testing is performed on a treadmill than on a bicycle ergometer.

PMID- 15250233
TI  - Extubation failure in the elderly.
AB  - To determine the causes, risk factors and complications of planned extubation
      failure of critically ill elderly patients, we conducted a prospective study of
      175 consecutive patients (> or = 70 years old) admitted with respiratory failure.
      Thirty-six (21%) failed extubation within 72 h after planned extubation. Compared
      to a younger age group (< 70 years old) matched for severity of illness,
      inability to handle secretions (20%) was the most common reason of airway causes
      leading to extubation failure in the elderly while upper airway obstruction (22%)
      was the predominant cause in the control group. As for nonairway causes, COPD
      related hypercapnic respiratory failure accounted for the majority of cases in
      both groups. After adjusting for severity of illness, elderly patients who
      required reintubation had a higher risk of developing nosocomial pneumonia. The
      presence of underlying pulmonary disease (odds ratio (OR), 2.9; 95% confidence
      interval (CI) 1.2-6.9), length of intubation > 4 days (OR, 4.3; 95% CI 1.8-10.2),
      and albumin levels < 2.5 g/dl (OR, 2.7; 95% CI 1.2-6.7) were independently
      associated with extubation failure in the old. Objective measurements of cough
      strength and secretion volume are needed to reduce the morbidity of elderly
      patients at risk for extubation failure.

PMID- 15250234
TI  - Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive
      substances in patients with community acquired pneumonia.
AB  - BACKGROUND: Bacterial pneumonia involves influx of activated phagocytes into
      distal airways. These cells release oxidants including H2O2, that may be exhaled
      or induce peroxidative damage to lung tissues with formation of thiobarbituric
      reactive substances (TBARs). STUDY OBJECTIVES: To determine whether
      concentrations of H2O2 and TBARs in exhaled breath condensate (EBC) is elevated
      and correlate with systemic response to pneumonia during 10 days of hospital
      treatment. DESIGN: The concentration of H2O2 and TBARs was measured in EBC of 43
      inpatients with community acquired pneumonia (CAP) and 20 healthy never smoked
      subjects over 10 days and were accompanied by monitoring of WBC count, serum
      concentration of C-reactive protein (CRP) and peroxyl radical-trapping capacity.
      RESULTS: Patients with CAP exhaled 4.6-, 3.7-, 3.9-, 3.3-times more H2O2 than
      healthy controls at 1st, 3rd, 5th and 10th day of treatment (P<0.05),
      respectively. EBC concentrations of TBARs were elevated at 1st and 3rd day. H2O2
      and TBARs levels decreased along with treatment course. Correlation (P<0.05) was
      found between H2O2 levels and CRP and WBC count (r = 0.31) at 1st day and between
      TBARs and CRP at 5th (r = 0.34) and 10th day (r = 0.46). The mean H2O2 exhalation
      estimated over ten days of treatment correlated with pneumonic chest X-ray score
      (r = 0.42), CRP levels (r = 0.46) and WBC count (r = 0.33) at admission (P<0.05).
      CONCLUSIONS: Pneumonia is accompanied by oxidative stress in airways that
      moderately correlates with intensity of systemic inflammatory response.
      Determination of H2O2 in EBC may be helpful for non-invasive monitoring of
      oxidants production during lower respiratory tract infection.

PMID- 15250235
TI  - Unilateral vocal cord palsy: a non-psychogenic cause of vocal cord dysfunction.
AB  - We believe this to be the first case report of VCD occurring in a patient with an
      underlying unilateral paralysis of the vocal cord. VCD, though rare, should be
      considered in any patient presenting as asthma who does not respond to
      conventional treatment. Physicians need to remain aware of the aetiological, co
      diagnosis or causative factors that can be associated with VCD.

PMID- 15250236
TI  - Improved ventilatory function associated with relief of chest pain in a patient
      with Kartagener's syndrome treated by subcutaneous analgesia.

PMID- 15250237
TI  - Exhaled breath condensate acidification in acute lung injury.

PMID- 15250238
TI  - Proliferation and differentiation of neural stem cells in adult rats after
      cerebral infarction.
AB  - OBJECTIVE: To investigate proliferation and differentiation of neural stem cells
      in adult rats after cerebral infarction. METHODS: Models of cerebral infarction
      in rats were made and the time-course expression of bromodeoxyuridine (BrdU),
      Musashi1, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen
      (NeuN) were determined by immunohistochemistry and immunofluorescence staining.
      BrdU and Musashi1 were used to mark dividing neural stem cells. GFAP and NeuN
      were used to mark differentiating neural stem cells. RESULTS: Compared with
      controls, the number of BrdU-labeled and BrdU-labeled with Musashi 1-positive
      cells increased strikingly 1 day after cerebral infarction; approximately 6 fold
      with a peak 7 days later; markedly decreased 14 days later, but was still
      elevated compared with that of controls; decling to the control level 28 days
      later. The number of BrdU-labeled with GFAP-positive cells nearly remained
      unchanged in the hippocampus after cerebral infarction. The number of BrdU
      labeled with NeuN-positive cells increased strikingly 14 days after cerebral
      infarction, reached maximum peak in the hippocampus 28 days after cerebral
      infarction in rats. CONCLUSION: Cerebral infarction stimulate proliferation of
      inherent neural stem cells and most proliferated neural stem cells differentiate
      into neurons.

PMID- 15250239
TI  - Production in Pichia pastoris and characterization of genetic engineered chimeric
      HBV/HEV virus-like particles.
AB  - OBJECTIVE: To investigate the presentation of a neutralization epitope-containing
      peptide antigen of hepatitis E virus (HEV) on chimeric virus-like particles
      (VLPs) of hepatitis B surface antigen (HBsAg). METHODS: The gene fragment
      corresponding to amino acids (aa) 551-607 (HEnAg) of HEV capsid protein, which
      contains the only neutralization epitope identified to date, was fused via a
      synthetic glycine linker in frame with the gene of HBsAg. The resulted fusion
      gene was then integrated through transformation into the genome of Pichia
      pastoris under the control of a methanol-induced alcohol oxidase 1 (AOX1)
      promoter and expressed intracellularly. The expression products in the soluble
      cell extracts were characterized by Western blot, ELISA, CsCl density gradient
      analysis, and electron microscopic visualization. RESULTS: The novel fusion
      protein incorporating HBsAg and the neutralization epitope-containing HEnAg was
      expressed successfully in Pichia pastoris with an expected molecular weight of
      approximately 32 kD. It was found to possess the ability to assemble into
      chimeric HBV/HEV VLPs with immunological physical and morphological
      characteristics akin to HBsAg particles. Not only did the chimeric VLPs show high
      activity levels in a HBsAg particle-specific ELISA but they were also strongly
      immunoreactive with hepatitis E (HE) positive human serum in a HEV specific
      ELISA, indicating that HEnAg peptide fragments were exposed on VLP surfaces and
      would be expected to be readily accessible by cells and molecules of the immune
      system. Similarity between chimeric VLPs to highly immunogenic HBsAg particles
      may confer good immunogenicity on surface-displayed HEnAg. CONCLUSION: The
      chimeric HBV/HEV VLPs produced in this study may have potential to be a
      recombinant HBV/HEV bivalent vaccine candidate.

PMID- 15250240
TI  - Significance of MMP-2 and TIMP-2 mRNA expressions on glomerular cells in the
      development of glomerulosclerosis.
AB  - OBJECTIVE: To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat
      mesangial cells (MsC) and in human diseased glomeruli, and to explore their
      significance in the development of glomerulosclerosis. METHODS: The expressions
      of MMP-2, TIMP-2, and Col IV mRNA on cultured rat MsC stimulated by IL-1 or/and
      TGF-beta1 were investigated through Northern blot analysis. The levels of MMP-2
      and TIMP-2 mRNA expressions and immunoreactivity of PCNA and Col IV in human
      diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were
      examined by in situ hybridization and immunohistochemistry, respectively.
      RESULTS: The levels of MMP-2, TIMP-2, and Col IV mRNA expressions were markedly
      increased on cultured rat MsC stimulated by IL-1 or/and TGF-beta1. Meanwhile,
      upregulation of MMP-2 and TIMP-2 mRNA expressions was confirmed in diseased
      glomeruli from patients with various subtypes of LN, and was closely related to
      the positive cell number of PCNA presentation and deposition of Col IV in
      glomeruli. CONCLUSION: The results suggest that the over-expressions of MMP-2 and
      TIMP-2 mRNA on glomerular cells might play a critical role in the development of
      glomerulosclerosis.

PMID- 15250241
TI  - Effects of cyclooxygenase-2 antisense vector on proliferation of human
      cholangiocarcinoma cells.
AB  - OBJECTIVE: To transfect antisense vector of human cyclooxygenase-2 (COX-2) gene
      into COX-2 highly expressing cholangiocarcinoma cell line QBC939 and explore its
      biological activities and role in carcinogenesis. METHODS: QBC939 cells were
      transfected with antisense vector of human COX-2 gene using LipoVec transfecting
      technique. Transfected cells were selected with G418; COX-2 mRNA was examined
      using reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein
      expression was detected by immunocytochemistry using isozyme selective
      antibodies. The proliferative status of transfected cells was measured by using
      methabenzthiazuron (MTT) assay; Cell cycle and apoptosis were analyzed by using
      flow cytometry. RESULTS: RT-PCR showed a lower COX-2 mRNA level in antisense
      vector transfected cells and immunocytochemistry showed a weaker COX-2 protein
      expression in antisense vector transfected cells. The antisense vector
      transfected cells proliferative index decreased significantly (P < 0.01), the
      percentage of S phase decreased remarkably (P < 0.05) in antisense vector
      transfected cells (9.27% +/- 1.91%) compared with that in QBC939 cells without
      transfection(16.35% +/- 2.87%), and the percentage of G0/G1 phase increased
      remarkably (P < 0.05) in antisense vector transfected cells (75.16% +/- 4.13%)
      compared with that in QBC939 cells without transfection (57.31% +/- 10.16%).
      Transfection with antisense vector of human COX-2 gene had no significant
      influence on the apoptosis in QBC939 cells (P > 0.05). CONCLUSION: Transfection
      with antisense vector of human COX-2 gene could inhibit the proliferation of
      human cholangiocarcinoma QBC939 cells.

PMID- 15250242
TI  - Analysis of interleukin-1 receptor antagonist gene polymorphism in Chinese
      patients with Alzheimer's disease.
AB  - OBJECTIVE: To identify an interaction between the interleukin-1 receptor
      antagonist gene polymorphism and risk of Alzheimer's disease. METHODS: The study
      included 117 healthy controls, 85 patients with Alzheimer's disease in a
      Northeastern Chinese population of Han nationality. Genotypes were determined by
      a polymerase chain reaction amplification of the intron 2 fragment, harbouring a
      variable number of short tandem nucleotide sequences. Amplification products were
      separated on a 2% agarose gel. RESULTS: The allele 2 frequency was 27% in healthy
      controls, and 21% in patients with Alzheimer's disease. Thus for allele 2 as well
      as for all other alleles, genotypes, or carriage rates, no significant
      differences compared with controls. CONCLUSIONS: No association of interleukin-1
      receptor antagonist gene polymorphism with Alzheimer's disease was identified in
      this population. It is also possible that the increased risk and disease
      modifying effects are caused by linkage disequilibrium with other genomic
      variants in other nearby genes.

PMID- 15250243
TI  - Microsurgical treatment of occupying-space lesions of brainstem.

PMID- 15250244
TI  - Finding potential ligands for PDZ domains by tailfit, a JAVA program.
AB  - OBJECTIVE: To deduce all potential ligands undiscovered experimentally by
      searching all the proteins containing same C-termini, which can bind a certain
      PDZ domain. METHODS: We developed a JAVA program for searching short exact
      sequence matches at C-terminus. According to the known C-termini, which PDZ
      domains recognized experimentally, Swissprot database has been searched by this
      program for all potential ligands. RESULTS: Some PDZ domains may have more
      potential ligand proteins, which are undiscovered yet experimentally. These
      bioinformatic results also provide clues for studying functions of hypothetical
      proteins and PDZ domains' protein interactions in many different organisms.
      CONCLUSION: The results may provide useful clues for discovering potential
      functions of hypothetical proteins and new functions of known proteins.

PMID- 15250245
TI  - Prognostic factors for deep situated malignant gliomas treated with linac
      radiosurgery.
AB  - OBJECTIVE: To study the function of radiosurgery on malignant glioma by analyzing
      prognostic factors affecting malignant gliomas treated with linac radiosurgery.
      METHOD: Fifty-eight patients with deep situated malignant gliomas, aged 7 to 70
      years, 28 anaplastic astrocytomas and 30 glioblastomas multiforme were analyzed.
      The median volume of tumor was 10.67 cm3, and median prescription dose for linac
      radiosurgery was 20 Gy. Results were analyzed with Kaplan-Meier curve and Cox
      regression. RESULT: In follow-up 44.8 percent tumors (26 patients) decreased in
      size. Median tumor local control interval was 10 months, 15 months for anaplastic
      astrocytomas, and 9 months for glioblastoma multiforme. Tumor local control
      probability was 37.9 percent for 1 year and 10.3 percent for 2 years. Median
      survival was 22.5 months for anaplastic astrocytoma, 13 months for glioblastoma
      multiforme, and 15 months for all patients. The survival probability was 79.3
      percent at 1 year and 20.6 percent at 2 years. Isocenter numbers and tumor volume
      were the prognostic factors for tumor control, but conformity index was the
      prognostic factor for survival by Cox regression analysis. Considering pathology,
      only isocenter number and target volume significantly affected tumor control
      interval. Complications appeared in 44.8 percent patients and the median interval
      of complication onset was 8 months. Symptomatic cerebral edema was observed in
      31.0 percent patients. CONCLUSION: Linac radiosurgery can effectively improve
      tumor local control and prolong survival for deep situated malignant gliomas.

PMID- 15250246
TI  - Basic fibroblast growth factor gene transfection to enhance the repair of
      avascular necrosis of the femoral head.
AB  - OBJECTIVE: To explore a new method for the therapy of avascular necrosis of the
      femoral head. METHOD: The recombinant plasmid pCD-rbFGF was mixed with collagen
      and was implanted in the necrotic femoral head. Expression of basic fibroblast
      growth factor (bFGF) was examined by RT-PCR and immunohistochemical method.
      Repair of the femoral head was observed by histological and histomorphometric
      analysis. RESULT: Expression of bFGF was detected in the femoral head transfected
      with bFGF gene, indicating significant increase of angiogenesis 2 weeks after
      gene transfection and increased new bone formation 8 weeks after gene
      transfection on histomorphometric analysis (P< 0.01). CONCLUSION: Transfection of
      bFGF gene enhances bone tissue angiogenesis. Repair in osteonecrosis would be
      accelerated accordingly.

PMID- 15250247
TI  - Response of early stage bulky cervical squamous carcinoma to preoperative
      adjuvant chemotherapy.
AB  - OBJECTIVE: To investigate the potential role of preoperative adjuvant
      chemotherapy on early stage cervical squamous carcinoma with bulky tumor.
      METHODS: One hundred and forty-five patients with cervical squamous cancer stages
      Ib-IIa were investigated, among which 17 patients with bulky tumors (> or = 4 cm)
      were managed by cisplatin-based chemotherapy for 1-2 courses followed by radical
      hysterectomy and pelvic lymphadenectomy (BC group). The change of tumor size,
      pelvic lymph nodes metastasis, cervical wall invasion, the involvement of
      surgical specimen margin, and the blood loss during operation were assessed after
      operation and compared with those in 51 patients with bulky tumors (BN group) and
      77 patients with small local tumors (S group) who underwent surgery directly.
      RESULTS: (1) The tumor size of 17 patients in BC group were decreased in various
      degrees after chemotherapy, with 13 patients of clinical effectiveness (76.47%).
      And the responsiveness pertained to neither histological differentiation nor size
      of local tumors. (2) Post-operative histology has showed that patients in BC and
      BN group have higher incidence of lymph node metastasis and deep cervical
      infiltration (5/68 and 3/68, respectively) than in S group (1/77 and 1/77,
      respectively) while with no statistical significance. (3) Blood loss during
      operation in BC group was less than BN and S group. (4) Seventeen patients,
      including those underwent surgeries of vaginal prolongation and/or ovarian
      transposition, appeared disease-free survival within the follow-up time.
      CONCLUSIONS: Most of patients with bulky early stage cervical squamous carcinoma
      are sensitive to cisplatin-based chemotherapy, which could greatly reduce local
      tumor size and in turn facilitate the following operation by well controlling
      blood loss.

PMID- 15250248
TI  - Clinical significance of serum cytokines IL-1beta, sIL-2R, IL-6, TNF-alpha, and
      IFN-v in acute coronary syndrome.
AB  - OBJECTIVES: To explore serum cytokines levels (including IL-1beta, sIL-2R, IL-6,
      TNF-alpha, and IFN-upsilon) and their significance in patients with acute
      coronary syndrome (ACS) and the subsequent follow-ups, with attempt to estimate
      the role of various serum inflammatory markers in the diagnosis and assessment of
      ACS. METHODS: The study population include 40 patients with acute myocardial
      infarction (AMI), 40 patients with unstable angina pectoris (UAP), and 40
      controls. Among the 80 patients, 60 patients attended a follow up 4 months later.
      Serum inflammatory markers including IL-1beta, slL-2R, IL-6, TNF-alpha, and IFN
      upsilon were measured by enzyme linked immunosorbent assay. RESULTS: Serum IL
      1beta, sIL-2R, IL-6, TNF-alpha were significantly higher in AMI group or UAP
      group compared to the control group and became significantly lower 4 months later
      in the follow-up patients. Serum levels of IFN-upsilon shows no significant
      difference between AMI group or UAP group and controls, also showing no
      significant change when measured in follow up patients. There was no correlation
      between serum creatine kinase-MB isoenzyme levels and serum inflammatory markers
      either in UAP or AMI group. Furthermore, when divided into two subgroups using
      Wagner's QRS scoring system in the AMI group, there is no difference of each
      serum inflammatory marker between < or = 6 scores group and > 6 scores group.
      CONCLUSION: Serum levels of certain inflammatory markers may have some diagnostic
      value for ACS, and can be a useful marker reflecting disease stability.

PMID- 15250249
TI  - A case of M2a with complex chromosome aberrations obtained complete remission
      through modified As2O3 medication.

PMID- 15250250
TI  - Role of ERK1/2 kinase in cisplatin-induced apoptosis in human ovarian carcinoma
      cells.
AB  - OBJECTIVE: To investigate the role of extracellular regulated kinase (ERK1/2)
      pathway in cisplatin-induced apoptosis in human ovarian carcinoma cells. METHODS:
      Cisplatin-induced apoptosis were stained with DAPI and was assessed
      microscopically in human epithelial adenocarcinoma ovarian cell line SKOV3 cells.
      ERK activation was determined by Western blotting using an anti-phospho-ERK
      antibody to detect ERK activity. The effect of PD98059 on ERK activity induced by
      cisplatin was detected by MTT assay. RESULTS: Marked apoptosis of SKOV3 cells
      resulted from 48 hours treatment with 20 microg/mL cisplatin. Strong activation
      of ERK was led to by 15 microg/mL cisplatin. Dose response and time course of
      cisplatin induced apoptosis in SKOV3 cells. Cisplatin-induced ERK activation
      occurred at 12 hours and increased to highest induction at 24 hours by Western
      blotting. The effect of PD 98059 on ERK activity induced by cisplatin at the
      concentration of 100 micromol/L PD 98059. Statistically significant decreased in
      cell survival were observed with 100 micromol/L PD 98059 at 15 and 20 microg/mL
      cisplatin (P < 0.05). CONCLUSIONS: Cisplatin activates the ERK signaling pathway
      in ovarian cancer cell line SKOV3. Inhibition of ERK activity enhances
      sensitivity to cisplatin cytotoxity in ovarian cancer cell line SKOV3. Evaluation
      of ERK activity could be useful in predicting which ovarian cancer will response
      most favorably to cisplatin therapy.

PMID- 15250251
TI  - Diagnosis and treatment of malignant pancreatic endocrine tumour.
AB  - OBJECTIVE: To summarize our experience in the diagnosis and treatment of
      malignant pancreatic endocrine tumour. METHODS: We retrospectively reviewed 36
      cases of malignant pancreatic endocrine tumours in our hospital from July 1987 to
      April 2002, and summarized its clinical features. RESULTS: Liver metastasis was
      the main malignant manifestation of malignant pancreatic endocrine tumours
      (incidence rate 72.2%). Removals of primary lesion and isolated hepatic
      metastatic lesion were means of curative therapy. Interventional chemotherapy was
      an important adjuvant treatment. CONCLUSION: Comprehensive therapy plays an
      important role in improving the prognosis of malignant pancreatic endocrine
      tumour.

PMID- 15250252
TI  - Anti-proliferation effect of oridonin on HL-60 cells and its mechanism.
AB  - OBJECTIVE: To investigate the anti-proliferation effect of oridonin on leukemic
      HL-60 cells and its mechanism. METHODS: HL-60 cells in vitro in culture medium
      were given different concentrations of oridonin. The inhibitory rate of cells
      were measured by microculture tetrazolium (MTT) assay, cell apoptotic rate was
      detected by flow cytometry (FCM), morphology of cell apoptosis was observed by
      hoechst 33258 fluorescence staining, and the activity of telomerase was detected
      using telomere repeat amplification protocol (TRAP) PCR-ELISA before and after
      apoptosis occurred. RESULTS: Oridonin could decrease telomerase activity, inhibit
      growth of HL-60 cells, and cause apoptosis significantly. The suppression was
      both in time- and dose-dependent manner. Marked morphological changes of cell
      apoptosis including condensation of chromatin and nuclear fragmentation were
      observed clearly by hoechst 33258 fluorescence staining especially after cells
      were treated 48-60 hours by oridonin. CONCLUSIONS: Oridonin has apparent anti
      proliferation and apoptotic effects on HL-60 cells in vitro, decreasing
      telomerase activity of HL-60 cells may be one of its most important mechanisms.
      These results will provide strong laboratory evidence of oridonin for clinical
      treatment of acute leukemia.

PMID- 15250253
TI  - Modified Graeb criteria for predicting the post-hemorrhagic hydrocephalus in
      intraventricular hemorrhage.
AB  - OBJECTIVE: To set up a new grading system of intraventricular hemorrhage (IVH)
      and determine the value of predicting the probability of post-hemorrhagic
      hydrocephalus (PHH) in IVH. METHODS: We first modified the Graeb criteria, then
      compared the value of prediction for PHH assessed by the Graeb criteria with the
      modified Graeb criteria. One hundred and thirty one IVH patients were divided
      into two groups: the upper group (n = 67) and the lower group (n = 64). Gold
      standard of PHH was assessed by CT scan or by out-drainage. The diagnostic
      parameters such as sensitivity (SE), specificity (SP) were analyzed. In the
      cutoff point of SE and SP curves, diagnostic efficiency (DE), and Kappa value (K)
      were analyzed. The probability of PHH was estimated by binary logistic
      regressions. RESULTS: In all ventricular group, to Graeb criteria in the cutoff
      point, SE, SP, and K was 0.78, 0.84, and 0.60; and to modified Graeb criteria SE,
      SP, and K was 0.90, 0.84, and 0.74 respectively. The probability of PHH from
      point of 3-12 was 0.011, 0.032, 0.085, 0.212, 0.435, 0.689, 0.865, 0.949, 0.981,
      and 0.994 respectively according to modified Graeb criteria.

PMID- 15250254
TI  - Imaging diagnosis of thoracolumbar burst fractures.
AB  - OBJECTIVE: To review imaging use in the diagnosis of thoracolumbar burst
      fractures and to determine the diagnostic value of different imaging methods.
      METHODS: One hundred and fourteen patients with 120 thoracolumbar burst fractures
      were retrospectively reviewed. Plain radiographs were available in all cases; CT
      scans and MRI were obtained in 96 and 74 cases, respectively. RESULTS: A total of
      27 burst fractures were misdiagnosed as other types of fractures on radiographs
      alone, and accounted for 22.5% of all fractures. The results indicated that plain
      radiographs often fail to delineate the pathological features of thoracolumbar
      burst fractures, leading to delay in diagnosis. CONCLUSION: In regard to
      thoracolumbar injury diagnosis, burst fractures should be differentiated from
      compression fractures. CT should be routinely indicated and MRI examination, when
      necessary, may be simultaneously considered.

PMID- 15250256
TI  - Detection of six kinds of antiphospholipid antibodies in the serum of healthy
      volunteers.

PMID- 15250255
TI  - Effects of simvastain combined with omega-3 fatty acids on high sensitive C
      reactive protein, lipidemia, and fibrinolysis in patients with mixed
      dyslipidemia.
AB  - OBJECTIVE: To evaluate the effects of simvastatin combined with omega-3 fatty
      acids on high sensitive C-reactive protein (HsCRP), lipidemia, and fibrinolysis
      in coronary heart disease (CHD) and CHD risk equivalent patients with mixed
      dyslipidemia. METHODS: A randomized, double-blind placebo controlled and parallel
      group trial was conducted. Patients with CHD and CHD risk equivalents with mixed
      dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following
      with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch)
      reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while
      triglyceride (TG) > or = 200 mg/dL and < 500 mg/dL, was combined with omega-3
      fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on
      HsCRP, total cholesterol (TC), LDL-ch, high-density lipoprotein cholesterol (HDL
      ch), TG, lipoprotein (a) [LP (a)], apolipoprotein A1 (apoA1), apolipoprotein B
      (apoB), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen
      activator (tPA) were investigated. Forty patients finished the study with each
      group consisting of twenty patients. RESULTS: (1) There were significant
      reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 +/- 2.77 mg/L
      (38.5%), 94.0 +/- 65.4 mg/dL (31.1%), 13.3 +/- 22.3 mg/dL (6.3%), 0.78 +/- 1.60
      respectively in the omega-3 fatty acids group (P < 0.01, < 0.001, < 0.05, < 0.05)
      compared to the baseline. HsCRP and triglyceride reduction were more significant
      in omega-3 fatty acids group compared to the placebo group (P = 0.021 and 0.011
      respectively). (2) In the omega-3 fatty acids group, the values and percentage of
      TG reduction had a significantly positive relation with HsCRP reduction (r = 0.51
      and 0.45, P = 0.021 and 0.047 respectively). CONCLUSION: In CHD and CHD risk
      equivalent patients with mixed dyslipidemia, dyslipidemia's therapeutic effect
      using simvastatin and omega-3 fatty acids may result from not only the
      combination of lipid adjustment, but also enhancement of their own nonlipid
      influences.

PMID- 15250257
TI  - Apolipoprotein E gene polymorphisms and risk for coronary artery disease in
      Chinese Xinjiang Uygur and Han population.
AB  - OBJECTIVE: To examine the relationship between apolipoprotein E (Apo E) gene
      polymorphism and risk of coronary artery disease (CAD), analyzing association of
      polymorphism with classical risk factors. METHODS: A total of 124 patients
      (including 84 Han population and 40 Uygur population) with angiographically
      verified CAD or myocardial infarction were prospectively evaluated. Data
      referring to hypertension, diabetes, and tobacco consumption were recorded. The
      levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo
      A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124
      patients and 70 controls. In order to determine Apo E genotypes, DNA was PCR
      amplified and digested with HhaI. The genetic polymorphism of Apo E is due to
      three common alleles, epsilon (epsilon) 2, epsilon3, epsilon4, at a single
      autosomal gene locus. These alleles determine the six phenotypes E2/2, E3/3,
      E4/4, E4/2, E4/3, and E3/2. RESULTS: In Uygur population, the frequency of the
      epsilon2, epsilon3, and epsilon4 was 0.155, 0.648, and 0.197 respectively. In Han
      population, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.081,
      0.772, and 0.146 respectively. In the patient group, the frequency of the
      epsilon2, epsilon3, and epsilon4 was 0.060, 0.758, and 0.182 respectively. In the
      control group, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.193,
      0.671, and 0.136 respectively. epsilon2 frequency of Uygur' patients and controls
      was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL)
      cholesterol, TC, and TG values tended to decrease from the Apo E-4 phenotypes to
      Apo E-2 phenotypes. When deletion polymorphism of epsilon2 was compared with the
      common risk factors for CAD, its risk ratio (RR) is 4.38. CONCLUSIONS: These
      studies confirm and find that Apo E phenotype distribution in Uygur population
      differs significantly from that in Han population in Xinjiang. CAD patients have
      significantly lower epsilon2 allele and slightly higher epsilon3 or epsilon4
      allele frequency than controls, especially in Uygur population. It shows
      protective effects of epsilon2 on CAD.

PMID- 15250258
TI  - Effects of TGF beta1 autocrine blockage on osteosarcoma cells.
AB  - OBJECTIVE: To evaluate the effects of transforming growth factor beta1 (TGFbeta1)
      autocrine blockage on proliferation activity and drug sensitivity of
      osteosarcoma. METHODS; Northern blot, MTT determination, and 3H thymidine
      incorporation were used to investigate the effects of antisense TGF beta1 gene on
      osteosarcoma. RESULTS: The proliferation of osteosarcoma cells transfected by
      antisense TGF beta1 gene was suppressed markedly, and adriamycin sensitivity was
      significantly increased. CONCLUSION: Blockage of osteosarcoma cells TGF beta1
      autocrine loop inhibits cell proliferation and enhances chemotherapy sensitivity.

PMID- 15250259
TI  - Postoperative hemodynamic parameter follow up in children with severe pulmonary
      hypertension due to ventricular septal detect.

PMID- 15250261
TI  - [Chronic nephritic syndrome].

PMID- 15250260
TI  - [Continuous dialysis therapy for patients with diabetic nephropathy].

PMID- 15250262
TI  - [ADPKD patients on dialysis].

PMID- 15250263
TI  - [Hypertensive patients with renal lesion].

PMID- 15250264
TI  - [Nephropathies in patients with collagen diseases].

PMID- 15250265
TI  - [Decision in timely initiation of hemodialysis therapy].

PMID- 15250266
TI  - [Management of pediatric chronic renal failure].

PMID- 15250267
TI  - [Hemodialysis for chronic renal failure in the elderly].

PMID- 15250268
TI  - [Management of cardiac complications in patients with end stage renal failure].

PMID- 15250269
TI  - [Pulmonary complications of chronic renal failure].

PMID- 15250270
TI  - [Blood purification for patients with chronic renal failure accompanied by severe
      liver disease].

PMID- 15250271
TI  - [Treatment of uremic patients with high bleeding risk].

PMID- 15250272
TI  - [Treatment for chronic kidney failure with cerebrovascular disease].

PMID- 15250273
TI  - [Guidelines for drug administration for dialysis patients].

PMID- 15250274
TI  - [Body fluid balance in uremic patients].

PMID- 15250275
TI  - [Imaging modalities for evaluation of cardiac function in patients with chronic
      hemodialysis].

PMID- 15250276
TI  - [Abnormalities in electrolyte and acid-base homeostasis in uremic patients].

PMID- 15250277
TI  - [Imbalance of trace elements in uremic patients].

PMID- 15250278
TI  - [Calcium and phosphate metabolism in dialysis patients].

PMID- 15250279
TI  - [Management of blood glucose in diabetic patients undergoing dialysis therapy].

PMID- 15250280
TI  - [Dyslipidemia in renal failure].

PMID- 15250281
TI  - [Protein and amino acid metabolism disorders in hemodialysis patients].

PMID- 15250282
TI  - [Purine metabolism in patients with renal failure].

PMID- 15250283
TI  - [Vitamin status in chronic renal failure].

PMID- 15250284
TI  - [Changes in platelets, coagulation and fibrinolysis in patients with chronic
      renal failure].

PMID- 15250285
TI  - [Renin-angiotensin-aldosterone system].

PMID- 15250286
TI  - [Glucocorticoids in end stage renal disease].

PMID- 15250287
TI  - [Sex hormones].

PMID- 15250288
TI  - [Thyroid hormone].

PMID- 15250289
TI  - [Abnormalities in parathyroid hormone and calcitonin associated with uremia].

PMID- 15250290
TI  - [Growth hormone / prolactin].

PMID- 15250291
TI  - [Cathecholamine].

PMID- 15250292
TI  - [Prostaglandin/bradykinin].

PMID- 15250293
TI  - [Natriuretic peptide].

PMID- 15250294
TI  - [Endothelin].

PMID- 15250295
TI  - [Activin].

PMID- 15250296
TI  - [Adrenomedullin].

PMID- 15250297
TI  - [Immune deficiency].

PMID- 15250298
TI  - [Cytokine].

PMID- 15250299
TI  - [Hemodialysis-associated hypertension; pathophysiology and therapy].

PMID- 15250300
TI  - [Hemodialysis-related hypotension].

PMID- 15250301
TI  - [Arrhythmia and conduction abnormalities in hemodialysis patients].

PMID- 15250302
TI  - [Ischemic heart disease].

PMID- 15250304
TI  - [Heart failure].

PMID- 15250305
TI  - [Dialysis disequilibrium syndrome].

PMID- 15250306
TI  - [Gastric haemorrhagic mucosal lesions in hemodialysis patients with special
      attention to iron ion depositions in gastric mucosa and reactive oxygen species].

PMID- 15250303
TI  - [Pericarditis].

PMID- 15250307
TI  - [Lower gastrointestinal complication of dialysis].

PMID- 15250308
TI  - [Hepatobiliary and pancreatic disease in dialysis patients].

PMID- 15250309
TI  - [Viral hepatitis in patients on chronic dialysis].

PMID- 15250310
TI  - [Tuberculosis in dialysis patients].

PMID- 15250311
TI  - [Deep seated fungal infection in dialysis patients].

PMID- 15250312
TI  - [Blood access graft infection in dialysis patients].

PMID- 15250313
TI  - [Renal anemia in hemodialysis patient].

PMID- 15250314
TI  - [Hyporesponsiveness to recombinant human erythropoietin therapy in anemic
      patients on hemodialysis].

PMID- 15250315
TI  - [Heparin-induced thrombocytopenia in patients on hemodialysis].

PMID- 15250316
TI  - [Methemoglobinemia as a complication of hemodialysis].

PMID- 15250317
TI  - [Bone disease in secondary hyperparathyroidism].

PMID- 15250318
TI  - [Adynamic bone disease].

PMID- 15250319
TI  - [Bone diseases in hemodialysis patients].

PMID- 15250320
TI  - [Arteriosclerosis in renal failure].

PMID- 15250321
TI  - [Vascular calcification in hemodialysis patients].

PMID- 15250322
TI  - [Diagnosis of and therapy for patients with dialysis amyloidosis].

PMID- 15250323
TI  - [Prevention of dialysis-related amyloidosis].

PMID- 15250324
TI  - [Autonomic neuropathy in patients with chronic kidney failure undergoing
      dialysis].

PMID- 15250325
TI  - [Dialysis encephalopathy].

PMID- 15250326
TI  - [Acquired renal cystic disease and renal cell carcinoma in dialysis patients].

PMID- 15250327
TI  - [Urolithiasis in hemodialysis patients].

PMID- 15250328
TI  - [Bladder cancer and prostate cancer in hemodialysis patients].

PMID- 15250329
TI  - [Generalized pruritus in hemodialysis patients].

PMID- 15250330
TI  - [Cutaneous manifestations prevalent in dialysis patients].

PMID- 15250331
TI  - [Eye complications in hemodialysis patients].

PMID- 15250332
TI  - [Use of tumor markers in patients on chronic hemodialysis].

PMID- 15250333
TI  - [Malignancies in chronic dialysis patients].

PMID- 15250334
TI  - [Aluminum and iron deposition in dialysis patients].

PMID- 15250335
TI  - [Sudden hearing loss in dialysis patients].

PMID- 15250336
TI  - [Sleep apnea syndrome in dialysis patients].

PMID- 15250337
TI  - [Psycho-nephrology in dialysis].

PMID- 15250338
TI  - [Cardiovascular surgery for dialysis patients].

PMID- 15250339
TI  - [Gastroenterological surgery and intraoperative blood purification therapy for
      patients with renal failure].

PMID- 15250340
TI  - [Pregnancy and delivery in patients with hemodialysis].

PMID- 15250341
TI  - [Introduction to dietary therapy for patients on dialysis].

PMID- 15250343
TI  - [Diet therapy for pediatric renal failure patients on dialysis].

PMID- 15250342
TI  - [Energy and nutrition in maintenance dialysis--significance of carnitine and
      cytokine in malnutrition].

PMID- 15250344
TI  - [Alcohol intake in dialysis patients].

PMID- 15250345
TI  - [Diet therapy for diabetic patients on dialysis].

PMID- 15250346
TI  - [Nutritional management in EN and TPN for dialysis patients].

PMID- 15250347
TI  - [Epidemiological aspects of chronic dialysis in Japan, U.S., and Europe].

PMID- 15250348
TI  - [Present status and future of dialysis therapy in Asia].

PMID- 15250349
TI  - [Medical facilities for dialysis].

PMID- 15250350
TI  - [Medical system reform as viewed by manufacturers of medical devices ].

PMID- 15250351
TI  - [Present status and measurement of incident x accident for blood purification
      therapy].

PMID- 15250352
TI  - [Risk management based on results of nationwide questionaire on medical
      accidents].

PMID- 15250353
TI  - [Analysis and management for medical accident and near miss events ( Ministry of
      Health, Welfare and Labor)].

PMID- 15250354
TI  - [Present condition in accident prevention in hemodialysis units].

PMID- 15250355
TI  - [Practice of clinical path].

PMID- 15250356
TI  - [Concepts and practical problems in informed consent].

PMID- 15250357
TI  - [Comparison of the principles in dialysis discontinuation in Western countries
      and Japan].

PMID- 15250358
TI  - [Nursing system and challenge of aged dialysis patients or those requiring
      nursing care].

PMID- 15250359
TI  - [Long-term hemodialysis and nursing care insurance--care at intermediate welfare
      facilities for the elderly needing long-term hemodialysis].

PMID- 15250360
TI  - [Role of the social case worker in dialysis].

PMID- 15250361
TI  - [Social rehabilitation and social environment for dialysis patients wishing a
      normal life].

PMID- 15250362
TI  - [QOL and self-care for dialysis patients].

PMID- 15250363
TI  - [Psycho-social problems of HD patients].

PMID- 15250364
TI  - [Psychonephrology in hemodialysis patients].

PMID- 15250365
TI  - [Management of dialysis patients with mental disorder].

PMID- 15250366
TI  - [Sexual dysfunction in ESRD patients].

PMID- 15250367
TI  - [Oral complications in patients receiving hemodialysis].

PMID- 15250368
TI  - [Complications and prognosis in diabetic patients on chronic dialysis].

PMID- 15250369
TI  - [Therapeutic guidelines for renal anemia in Japan].

PMID- 15250370
TI  - [Appropriate iron supplementation in renal anemia treatment].

PMID- 15250371
TI  - [Whole-PTH assay--new method for assessment of parathyroid function].

PMID- 15250372
TI  - [Parathyroid intervention and surgical treatment in renal hyperparathyroidism].

PMID- 15250373
TI  - [Intravascular radiological treatment for patients with ADPKD].

PMID- 15250374
TI  - [Modality choice in end-stage renal disease].

PMID- 15250375
TI  - [Home dialysis].

PMID- 15250376
TI  - [Kidney transplantation update].

PMID- 15250377
TI  - [Next generation of artificial kidney therapy].

PMID- 15250378
TI  - [Bioartificial kidneys].

PMID- 15250379
TI  - [Regenerative medicine in renal failure].

PMID- 15250380
TI  - [Disinfectants and the environment].

PMID- 15250381
TI  - [Study of dialysis outcomes and practice patterns].

PMID- 15250382
TI  - [A good clinical guideline is an orientational tool, not a checklist].
AB  - Lege artis procedures, medical standards as well as guideline contents ought to
      be defined by health care professionals themselves. Therefore the medical
      profession carries a great responsibility to both continuously optimise
      diagnostic and therapeutic methods as well as their results and adapt them to
      medical progress. Standards and guidelines cannot replace a doctor's
      responsibility towards his patients. They can help doctors to find the right
      answer but they are not check-off lists. The practical application of an evidence
      based guideline must result from a doctor's identification of a certain patient
      problem. This stage of identification is predominated by the individual doctor's
      internal evidence which reflects his medical knowledge, practical experience and
      the information arising from the individual relation between patient and doctor.

PMID- 15250383
TI  - [Medical standards and guidelines--definitions and functions].
AB  - Clinical practice guidelines are systematically developed statements to assist
      important professional and patient decisions about appropriate health care for
      specific circumstances. The main aim of Clinical Practice Guidelines (CPGs) is to
      promote and support good clinical practice and inform the public about it, while
      taking into account the resources available. There has always been a body of
      opinions providing guidance to individual professionals. The novel aspect of
      evidence-based guidelines is both the systematic way in which they are developed
      and their explicit nature. CPGs must be developed using state-of-the-art
      methodology and be critically appraised before implementation is considered,
      though many use methods that are not robust or of uncertain quality or origin.
      Such clinical practice guidelines have several primary and secondary functions.
      They can be employed to support health care decisions and to provide information
      about cost effectiveness, be referred to in legal proceedings, and they can help
      to link research, education and practice. All these functions are dependent on
      each country's societal values and situation. The basic approaches are discussed
      in more detail according to the recommendations of the Council of Europe
      published in 2001.

PMID- 15250384
TI  - [The evidence base of clinical practice guidelines, health technology assessments
      and patient information as a basis for clinical decision-making].
AB  - Valid assessments of benefit and harm of health care interventions are derived
      from unbiased patient-based clinical trials. Bias sources may affect different
      study types in different ways, leading to varying validity of study results. The
      efficient transfer of relevant study results into medical practice is the main
      objective of evidence-based medicine. To archive this, systematic reviews
      summarising the study results with respect to a focussed question have proved a
      powerful tool. They can be used for decision making by individuals as well as
      evidence source for clinical practice guidelines, health technology assessment
      and patient information.

PMID- 15250385
TI  - [Economisation of medicine--standards and guidelines: adverse effects and their
      legal implications].
AB  - Evidence-based clinical guidelines are recommendations for physicians and as such
      only of limited use as binding standards for monitoring the quality of their own
      achievements. When the Federal Joint Committee translates such guidelines into
      directives for physicians, hospitals, sickness funds and the insured they must
      consider the legal quality of such guidelines in order to ensure that physicians
      may exercise discretion to the extent necessary to providing individual
      treatment. Evidence-based medical guidelines are suitable means of ensuring
      quality. They are also intended to guide physicians on the efficiency of their
      services. But combining clinical guidelines as disease profiles of DMPs with the
      risk adjustment system of sickness funds or an instrument of selective contracts
      between sickness funds and physicians carries the risk of excessive bureaucracy
      and limiting the clinical freedom of physicians.

PMID- 15250386
TI  - [Fragmentation of the doctor-patient relationship as a result of standardisation
      and economisation].
AB  - Standards, guidelines and evidence-based medicine are suitable means to
      strengthen the doctor-patient relationship, but will have the opposite effect if
      they are unrelated to the subject and fail to address the patient's needs. This
      may be the case with collective agreements in terms of socialised medicine which
      serve to restrict the patient's individuality in favour of rigid austerity
      measures and rationing. For this reason, rationing can only be a political
      instrument; it should never be applied to the doctor-patient relationship.
      Evidence-based medicine is another important decision-making tool that is also
      applicable to individual cases. Follow-on consequences regarding the law,
      science, politics and industry are often disregarded. The claims formulated in
      evidence-based and thus legally enforceable guidelines are going to increase the
      demands made on every individual doctor. The movement of evidence-based medicine
      can thus be understood as some kind of "enactment of knowledge". "Networks" are
      intended to soften hierarchies, reduce bureaucracy and keep pure market effects
      in check. But does this not often mean concealing the truth by putting old wines
      in new bottles? If economisation means financial pressure on time and personnel,
      then the impact on the doctor-patient relationship will generally have to be
      assessed negatively--as is usually the case. Financial pressure is intended to
      provide an incentive to make use of rationalisation reserves but we have long
      since reached the end of our tether. The result is rationing. This means time and
      staff rationing and thus a direct negative impact on the doctor-patient
      relationship. Thinking in terms of functions with the patient viewed as a market
      factor does nothing to benefit the doctor-patient relationship if the doctor is
      compelled to give in to this line because he cannot withstand the pressure. The
      introduction of KIS, KTQ, RIS, DRG and Risk Management Programmes as well as
      clinical pathways and telemedicine has the potential to bring about an
      improvement of the time and staff situation if the hoped-for release of such a
      potential did not immediately fall prey to the pressure of costs. Currently, the
      introduction of all these programmes means adding to the immense burden on
      medical doctors, which in turn will produce negative effects on time and
      personnel. If the application of the working time legislation is to be observed,
      then the hospital doctor is threatened with becoming either a temporary agency
      worker or a professional holiday-maker. If the doctor-patient relationship is to
      be strengthened then this can only be achieved through the quality of the medical
      services provided and humane patient care.

PMID- 15250387
TI  - [The impact of guidelines, standards and economic restrictions on clinical
      decision-making processes].
AB  - Guidelines aim at improving clinical decision-making. Contrary to textbooks and
      reviews that want to improve medical knowledge, guidelines try to influence
      medical behaviour. Scientific models of clinical decision-making such as the
      action theory and empirical data on the effects of guidelines suggest that
      guidelines will not always reach their goals but can instead even lead to a
      deterioration in the quality of medical care. Therefore there is a need for
      controlled clinical trials to investigate whether guideline-exposed physicians
      yield better patient outcomes than guideline-naive physicians. Guidelines should
      only be regarded as evidence-based if their positive effects have been
      empirically demonstrated.

PMID- 15250388
TI  - [Allocation of resources and restrictive standards in hospitals in the face of
      economic and personnel shortages].
AB  - The allocation of financial resources between both hospitals and the departments
      within a single hospital follows historically grown structures. Concepts on the
      basis of well-established factors for the systematic allocation of resources are
      rarely if ever used. Systematic approaches are needed, especially in times of
      decreasing resources, but they have to be grounded in a detailed understanding of
      both the customers and the products offered. The application of standards is a
      vital factor in order to simultaneously enhance operational efficiency and
      strategic effectiveness.

PMID- 15250389
TI  - [Influence of working time regulations on the organisation and quality of
      clinical workflow].
AB  - The present lecture is a personal report on changing working conditions for
      physicians in German hospitals over the last 20 years. Documentation, coding and
      other administrative requirements have constantly risen and will increase once
      again from 2004 onwards when the complete reimbursement system in German
      hospitals will be rearranged on the basis of diagnosis-related groups, though
      without providing an adequate workforce of professional coders. Moreover, the
      European Court ruled that any doctor's on-call hours spent in a hospital should
      be regarded as part of his full working time, which in Germany is presently
      restricted to an average 38.5 hours a week. Consequently, this will lead to a
      huge demand of personnel on the one hand and an increasing fragmentation of
      doctor-patient relationships on the other hand, as there will be a continuous
      change of doctors on duty. Here, it is outlined that this fragmentation will have
      a negative impact on treatment quality and education and training of future
      physicians.

PMID- 15250390
TI  - [How much quality loss can and will society afford?].
AB  - In Germany, there is an ever increasing gap between the legitimate claim to
      quality treatment and current health care reality. While the Republic of Germany
      still is among the world's best as regards the number of insured persons, health
      care expenditure and its share in gross national product, medical care has
      declined from top to medium quality. Underuse, overuse and misuse of health care
      resources have become noticeable, and patients are beginning to lose confidence
      in our healthcare system. Examples of deficit areas include the undersupply of
      care for many patients in the nursing sector, the life-threatening implications
      of trivialising diseases like sleep apnoea and the care of schizophrenic patients
      that is still lagging behind international standard. For many years German
      healthcare policy has only aimed at achieving cost containment, without
      simultaneously introducing drastic reforms to put an end to mismanagement. So far
      all attempts at reforming our healthcare system have only led to increased costs
      for the paying patients. In the face of this development the patients' demand for
      more information on healthcare system issues is rising and--due to better access
      to various novel information sources on the broad range of healthcare
      possibilities also--they are calling for improved medical care. The special focus
      is that modern, quality-oriented medicine will ultimately turn out to be the more
      efficient and cost-effective medicine.

PMID- 15250391
TI  - [The influence of medical standards, medical guidelines and economic restrictions
      on the standard of legal liability].
AB  - First we will have to identify the components determining the standard for
      medical liability in civil law cases. The civil courts have so far uniformly
      regarded the medical standard defined by physicians themselves as the standard of
      legal liability. Medical standards are based on scientific knowledge, practical
      experience and professional acceptance. Clinical guidelines can but need not
      necessarily reflect medical standards. Moreover, they cannot establish a
      standard. Second, on this basis the question will be whether economic
      restrictions should be allowed to alter the standard of legal liability. The
      answer depends, namely on what is meant by economic restrictions--rationalising
      or rationing? Rationalising need not be inconsistent with the standard. There are
      contradicting opinions in the legal literature about whether rationing is
      considered permissible. With regard to our social insurance system some authors
      point out that the highest possible standard is established by the statutory
      health insurance. With reference to the civil law, though, others demand that the
      medical standard must be given top priority. In accordance with the latter
      opinion rationing is only permitted in cases of a natural shortage of resources.
      Shortage of economic resources must not influence the standard of legal
      liability.

PMID- 15250392
TI  - [Do clinical guidelines and economic restrictions on health care affect the
      criminal liability of health care professionals?].
AB  - Criminal liability in connection with clinical guidelines relates to several
      different aspects: (1) It refers to the guideline authors' liability under
      criminal law in the case of faulty guidelines. (2) Guidelines do not constitute
      legally binding rules. They can only contribute to determining the standard for
      medical specialists. (3) There can and must not be any reversal in the burden of
      proof with criminal proceedings. (4) In case of a deviation from guidelines and a
      related breach of duty, the subjective aspect of negligence (i.e. the
      recognizability of danger) can often be inferred from the knowledge of the
      respective guideline that we can reasonably expect of the physician. (5) No
      physician who has adhered to the guidelines can regularly be accused of
      (subjective) negligence. (6) Problems may be encountered in cases where the topic
      in question has not been covered, but only peripherally touched upon by
      guidelines. For the sake of uniformity in our legal system, the individual
      physician must not be held criminally responsible for the lack of economic means.
      Possible solutions include: (1) relating the standard to the practically instead
      of the theoretically feasible, (2) investigating to what extent criminal
      liability may be limited by acceptability and possibility. The complete refusal
      to provide medical care under inadequate conditions may increase the endangerment
      of legally protected rights and therefore be unacceptable. Attempts to improve
      structures towards the standard may be regarded as meeting the requirements under
      criminal law.

PMID- 15250393
TI  - [Constitutional requirements for the regulation of medical practice].
AB  - Guidelines describe a systematically produced technical standard for medical
      decisions in different situations of medical treatment and therefore serve as
      guidance for both professionals and patients. They apply subject to the specific
      features of the individual case. Finally, their adoption as legal rules by the
      "joint self government" is only admissible if the requirements which will be
      developed in this article are fulfilled.

PMID- 15250394
TI  - [The binding quality of non-binding--the paradox of disease management
      guidelines].
AB  - The recommendations on "Medical Standard and Guidelines--Economisation of Medical
      Care" issued by the German Society of Medical Law (DGMR) critically focus on the
      binding effects of guidelines in the statutory health insurance system. But even
      after the Modernisation of the Statutory Health Insurance System Act (GMG) has
      been passed, concerns remain.

PMID- 15250395
TI  - Early milestones in the development of ion-exchange chromatography: a personal
      account.
AB  - Ion chromatography as we know it today was built on a foundation of knowledge
      accumulated over a period of many years. Here, we review some of the outstanding
      earlier achievements in ion-exchange chromatography. Beginning about 1947.
      Spedding and Powell at Iowa State published a series of papers describing
      practical methods for preparative separation of the rare earths by displacement
      ion-exchange chromatography. The same group then demonstrated the ion-exchange
      separation of 14N and 15N isotopes in ammonia. Beginning in the 1950s. Kraus and
      Nelson at Oak Ridge published numerous analytical methods for metal ions based on
      separation of their chloride, fluoride, nitrate or sulfate complexes by anion
      chromatography. In the period from about 1960 to 1980 many clever chromatographic
      methods for metal ion separations were reported by researchers throughout the
      world and automatic in-line detection was gradually introduced. A truly
      innovative method by Small, Stevens and Bauman at Dow Chemical Co. marked the
      birth of modern ion chromatography. Anions, as well as cations, could now be
      separated quickly and conveniently by a system of suppressed conductivity
      detection. A method for anion chromatography with non-suppressed conductivity
      detection was published by Gjerde et al. in 1979. This was followed by a similar
      method for cation chromatography in 1980. Ion chromatography as we know it today
      did not just happen. It was built on a solid foundation of knowledge that has
      accumulated over a period of many years. Revisiting the older ion-exchange
      chromatography serves not only to pay tribute to some remarkable accomplishments,
      but it can also be a learning experience. Trends and ideas in science tend to run
      in repeating cycles. Thus, an awareness of older work may provide inspiration for
      new research using improved contemporary technology. Selection of milestones is a
      rather personal matter. I chose to write about subjects of which I came to have a
      firsthand knowledge during my career. The topics selected are in roughly
      chronological order and cover the period from about 1945 to 1980. An effort has
      been made to explain the chemical principles as well as to recount the major
      accomplishments of the various research projects.

PMID- 15250396
TI  - Investigation of new chelation ion chromatography procedure to determine the
      surface composition of powdered metal oxide samples in the solid state.
AB  - Numerous tests have been conducted on the feasibility of characterizing the
      surfaces of metal oxide powders using HPLC. An in-line filter housing was
      modified to serve as a sample chamber to replace the sample loop. A gradient pump
      was used to gradually increase eluent acidity to find the conditions at which the
      surface of a metal oxide powder began to dissolve. The theoretical masses of
      surface monolayers of metal oxide powders were compared with the experimentally
      determined masses of dissolved material thought to be from the surface to test
      whether surface and bulk dissolution phenomena in acidic conditions are separable
      and quantifiable. A set of methods was tested that could first dissolve a metal
      oxide sample's surface, then separate and detect analyte species by chelation ion
      chromatography. Surface characterization by ion chromatography could be more cost
      effective than existing methods, and reveal chemical properties of the sample
      where existing methods only give physical composition and properties.

PMID- 15250397
TI  - Auto-regeneration of anion-trap columns for improved determination of silica by
      ion chromatography.
AB  - The goal of this project was to develop an automated method to regenerate the ATC
      3 trap columns that are used on the DX-800 on-line ion chromatography silica
      systems. The old method of regenerating the ATC-3 trap columns was to physically
      remove the trap columns from the silica system once every 2 weeks and manual
      regenerate them. A new automated regeneration method was developed by re-plumbing
      the silica system to allow 300 mM NaOH to run as the eluent. This regenerates the
      trap column automatically once every 24 h. The data have shown that regenerating
      the ATC-3 trap columns once per day improves the R.S.D. values for 250 ng/l
      silica analysis from 26.0 to 8.7%. The length of useful lifetime for the silica
      concentrator column was increased by an average of 9 months.

PMID- 15250398
TI  - Using ultrapure water in ion chromatography to run analyses at the ng/L level.
AB  - Thanks to enhanced capabilities, ion chromatography (IC) occupies an increasing
      position in many types of applications. Achieving ideal performances for an
      extended life-time can only be reached, however, if the IC system is operated in
      optimum experimental conditions. Among the various parameters that need to be
      controlled, water is particularly important, because it is used throughout the
      analysis, from sample preparation to column rinsing, elution, and mobile phase
      preparation. More and more, devices are included in IC systems to generate the
      eluent in situ, and ultrapure water becomes the major reagent. Data of pre
      concentration of high purity water show that detection limits at the ng/L level
      can be expected with water purified using the right combination of technologies.

PMID- 15250399
TI  - Automatic generation of ultra-pure hydroxide eluent for carbohydrate analysis of
      environmental samples.
AB  - High-performance anion-exchange chromatography coupled with pulsed amperometric
      detection under alkaline conditions has significantly improved our understanding
      of the function of carbohydrates in cycling of terrestrial carbon. The use of
      NaOH as an eluent has many advantages for anion analysis, but NaOH solutions are
      also an excellent trap for atmospheric CO2 resulting in eluent carbonate ion
      contamination. To minimize the carbonate contamination, eluent generation
      technology has been marketed that produces ultra-pure hydroxide (OH) eluents on
      demand. Application of this technology significantly reduced the amounts of OH
      present in the waste stream and provided faster chromatographic runs with greater
      sensitivity and precision for determining the monosaccharide composition from
      environmental samples. Minimizing the salt concentration to < or = 50 mm from
      acid hydrolysis extractions injected (25 microl injection volume) on column
      improved reproducibility of analyte retention times and separations. Eluent
      generation technology eliminated inconsistent OH eluent preparation that is often
      due to carbonate contamination. The contamination increases retention time
      variability for monosaccharides released by hydrolysis of biological samples.

PMID- 15250400
TI  - Optimizing the quadruple-potential waveform for the pulsed amperometric detection
      of neomycin.
AB  - Determination of neomycin is important for quality control of the pharmaceutical
      preparation. A quadruple-potential waveform used for pulsed amperometric
      detection of neomycin was investigated. The waveform cleans the electrode by
      application of a potential more negative than the potential limit to avoid the
      formation of gold oxide during applying positive potential to clean gold
      electrode, thus decreasing the dissolution resulting recession of the gold
      working electrode within gold oxide formation/reduction cycles in the triple
      potential waveform. Waveform parameters were optimized to maximize the signal-to
      noise ratio (S/N). The detection limit of neomycin B is lower than 0.01
      microg/ml. The linearity of framycetin (plotted as peak area of neomycin B)
      ranges from 0.05 to 100 microg/ml with correlation coefficient 0.9998. R.S.D. (n
      = 60) of the peak area of neomycin B is lower than 2%. The quadruple-potential
      waveform shows low detection limits and long-term reproducibility.

PMID- 15250401
TI  - New suppressor technology improves the ion chromatographic determination of
      inorganic anions and disinfection by-products in drinking water.
AB  - This paper describes a new suppressor technology for analyzing water samples
      using United States Environmental Protection Agency (EPA) methods 300.0 and
      300.1. The Alltech DS-Plus suppressor improves and simplifies anion analysis in
      drinking water. In addition to suppressing the carbonate mobile phase and
      enhancing the analyte signal like conventional ion chromatography (IC)
      suppressors, the DS-Plus suppressor removes carbonic acid (as dissolved carbon
      dioxide) from the suppressor effluent before detection (US patent Nos.: 6444475;
      6468804; others pending), lowering the background conductivity to near zero.
      Anions are detected in water background, improving sensitivity and lowering
      detection limits. The water-dip often seen with conventional suppressors is
      greatly reduced, improving fluoride quantification. The DS-Plus suppressor
      operates continuously without the need for external regenerants or switching
      valves. The performance of this new suppressor for analyzing water samples has
      been found to meet the EPA methods specifications.

PMID- 15250402
TI  - Ion chromatography for the determination of sulfate in STEALTH liposomes.
AB  - An ion chromatography (IC) method has been validated for the assay of sulfate ion
      content in the STEALTH liposome drug-delivery system (ALZA, Mountain View, CA,
      USA), which contains ammonium sulfate as an excipient. This method contains two
      assays. One assay determines the total sulfate ion content; the other determines
      the external sulfate ions. The total sulfate ion analysis measures the sulfate
      ion content of the formulation, inside and outside of the liposome. The analysis
      includes the disruption of the liposome bilayer with Triton-X, followed by
      dilution with 10% sucrose, and analysis using IC. The external sulfate analysis
      measures sulfate ions outside the liposome without disrupting the liposome
      structure. A neat sample of STEALTH liposome drug-delivery system is filtered
      through a 0.02 microm filter, and the filtrate is analyzed by IC. Sulfate ion is
      resolved on an anion exchange column and detected by a conductivity detector.
      Quantitation is performed by linear regression analysis of peak areas from a
      standard curve of sulfate ion containing at least five standard points. The
      method was validated for specificity, linearity, accuracy/recovery, precision,
      and stability of the standard and the sample. The validated method has been
      applied to the quantification of sulfate ion in STEALTH liposomes for product
      release and stability testing.

PMID- 15250403
TI  - Determination of monovalent inorganic anions in high-ionic-strength samples by
      electrostatic ion chromatography with suppressed conductometric detection.
AB  - A new ion chromatographic (IC) system has been established by using micelles of 3
      (N,N-dimethylmyristylammonio)propanesulfonate (Zwittergent 3-14) loaded onto a
      reversed-phase packed column as the separation column with an electronic rotary
      switching valve packed-bed suppressor for conductometric detection of inorganic
      anions. An aqueous H3BO3-Na2B4O7 solution has been demonstrated to be the most
      desirable eluent for this IC system. The relationship between retention time and
      the concentration of the borate eluent was determined for a series of model
      anionic analytes and this relationship was found to be opposite to that exhibited
      in a conventional anion-exchange IC system. The rapid elution and complete
      separation of monovalent inorganic anions were obtained by initially using a high
      concentration borate solution as the eluent for a short-period, and then
      switching to a lower-concentration borate eluent to complete the separation.
      Detection limits for nitrite, bromide, nitrate, and chlorate were 0.85, 0.88,
      0.95 and 4.8 microM, respectively, when a 7.0 mM Na2B4O7 eluent was used.
      Moreover, the ability to directly detect these monovalent anions in samples
      containing high concentrations of sulfate and/or chloride ions provided a major
      advantage of this approach.

PMID- 15250404
TI  - Qualification of an electro-deionization module via experimental design and ion
      chromatographic studies.
AB  - To meet the needs of the laboratory-water market, a modified electro-deionization
      (EDI) module has been developed to produce Type 2 purified water. An EDI module
      consists of desalting and concentrating fluidic compartments that are both filled
      with anion and cation ion-exchange resins; an anode and a cathode electrode are
      at opposite ends. In the design in this research, the anode electrode is
      segmented into three parts and individual dc amperages are applied to each
      segment; the cathode electrode is a single common electrode. Critical to the
      performance and longevity of this type of EDI module are: (1) the optimization of
      the applied dc amperages and (2) the ionic mass balance (i.e., the concentrations
      of specific and total ions of the RO feedwater to the module compared to the
      concentrations in the water exiting the module via the desalting and
      concentrating compartments). To determine a suitable current for each electrode
      pair, a full-factorial experimental design was developed and employed. For the
      application of this combination of amperages, the critical parameter of specific
      ion mass balance was determined using ion-chromatographic measurements.

PMID- 15250405
TI  - Analysis of sugar phosphates in plants by ion chromatography on a titanium
      dioxide column with pulsed amperometric detection.
AB  - This paper describes the development of a practical method for the analysis of
      sugar phosphates from the model higher plant Arabidopsis thaliana by high
      performance anion-exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD). The extraction method of sugar phosphates from higher plants was
      first optimized for HPAEC-PAD analysis. In order to improve the resolution in
      HPAEC-PAD, a column packed with titanium dioxide resin was used. The titanium
      dioxide column was used as a trap-column for sugar phosphates and nucleotides,
      for the removal of sample matrices. Sample pretreatment was achieved in-line and
      automatically using a six-port valve placed after the injection valve.

PMID- 15250406
TI  - Determination of bisphosphonates by ion chromatography-inductively coupled plasma
      mass spectrometry.
AB  - An ion chromatography-inductively coupled plasma mass spectrometry (IC-ICP-MS)
      was introduced in the analysis of bisphosphonates. Two compounds (alendronic acid
      and etidronic acid) were separated on a Dionex AS-7 anion-exchange column with
      dilute nitric acid employed as the mobile phase. The analytes were detected at
      m/z 31, as they contain phosphorus. The detection limits achieved were 0.20 mg l(
      1) for alendronic acid and 0.05 mg l(-1) for etidronic acid. Since the
      determination of phosphorus by ICP-MS is difficult due to polyatomic
      interferences at m/z 31 (15N16O+, 14N16O1H+, and 12C1H(3)16O+), a detailed study
      of the influence of plasma parameters on phosphorus and background signal was
      performed.

PMID- 15250407
TI  - Measurement of perchlorate in water by use of an 18O-enriched isotopic standard
      and ion chromatography with mass spectrometric detection.
AB  - Currently, the most promising analytical methodology for low-level determination
      and confirmation of perchlorate (ClO4-) in drinking water is ion chromatography
      followed by electrospray ionization mass spectrometric detection (IC-ESI-MS).
      However, there are still potentially limiting situations that must be considered
      when analyzing real world samples by IC-ESI-MS. They are: (1) co-elution of
      contaminants with fragment ions having the same m/z as ClO4-, (2) high background
      counts at the m/z of interest leading to a subsequent decrease in signal-to
      noise, (3) gradual loss of sensitivity occurring over time as the sampling cone
      and/or ion optics of the mass spectrometer are fouled, and (4) suppression of gas
      phase ion formation (ionization suppression) that can occur if high
      concentrations of contaminants co-elute with ClO4-. An internal standard whose
      response, on the column and in the electrospray, is similar to that of ClO4-
      would give the highest degree of accuracy possible in situations 3 and 4 listed
      above. Commercially available NaClO4 that was enriched with oxygen-18 was
      evaluated for its potential as an internal standard. The level of oxygen-18 (18O)
      enrichment was verified, the stability of the enriched ClO4- in aqueous solutions
      was determined, and method performance parameters such as method detection
      limits, accuracy, precision and ruggedness using the enriched ClO4 as an internal
      standard were determined. Internal and external calibration yielded similar
      results with respect to calibration, detection limits, and short-term precision.
      However, the enriched isotopic internal standard showed superior results with
      respect to ruggedness and percent recovery of spikes in ground water and
      synthetic water samples.

PMID- 15250408
TI  - Determination of trace-level haloacetic acids in drinking water by ion
      chromatography-inductively coupled plasma mass spectrometry.
AB  - A new method for the determination of nine haloacetic acids (HAAs) with ion
      chromatography (IC) coupled to inductively coupled plasma mass spectrometry (ICP
      MS) was developed. With the very hydrophilic anion-exchange column and steep
      gradient of sodium hydroxide, the nine HAAs could be well separated in 15 min.
      After suppression with an ASRS suppressor that was introduced in between IC and
      ICP-MS, the background was much decreased, the interference caused by sodium ion
      present in eluent was removed, and the sensitivities of HAAs were greatly
      improved. The chlorinated and brominated HAAs could be detected as 35ClO and 79Br
      without interference of the matrix due to the elemental selective ICP-MS. The
      detection limits for mono-, di-, trichloroacetic acids were between 15.6 and 23.6
      microg/l. For the other six bromine-containing HAAs, the detection limits were
      between 0.34 and 0.99 microg/l. With the pretreatment of OnGuard Ag cartridge to
      remove high concentration of chloride in sample, the developed method could be
      applied to the determination of HAAs in many drinking water matrices.

PMID- 15250409
TI  - Challenges encountered in extending the sensitivity of US Environmental
      Protection Agency Method 314.0 for perchlorate in drinking water.
AB  - Concerns about the potential adverse health effects of perchlorate at
      concentrations below the minimum reporting level (MRL) of US Environmental
      Protection Agency (EPA) Method 314.0 (generally recognized as 4.0 microg/l) have
      led to an interest in increasing the sensitivity of the method. This work
      describes the use of 2 mm columns with a large-loop direct injection method, a
      column concentration technique and this concentration technique with a background
      reduction step, to increase the sensitivity for the analysis of trace levels of
      perchlorate in high ionic strength matrices. The concentrator columns studied
      were the Dionex TAC LP-1 and a new Dionex high capacity Cryptand concentrator
      column. The use of a surrogate to monitor trapping efficiency for the
      concentration technique and the use of confirmational columns to minimize the
      potential for false positives are also discussed. The large-loop direct injection
      method and the column concentration methods provided acceptable data when the
      samples were pre-treated with solid phase pretreatment cartridges. The background
      reduction technique did not provide acceptable data with either of the
      concentrator columns evaluated.

PMID- 15250410
TI  - Detection of hypophosphite, phosphite, and orthophosphate in natural geothermal
      water by ion chromatography.
AB  - Current doctrine states that phosphorus is incorporated into cells in the
      pentavalent(V) oxidation state as orthophosphate. However, recent studies show
      that microorganisms contain enzymes used to metabolize reduced forms of
      phosphorous, including phosphite(III) and hypophosphite(I), which suggests that
      there is a natural source for these chemical species. This paper will discuss
      suppressed conductivity ion chromatography methods developed to detect
      hypophosphite, phosphite, and orthophosphate in a geothermal water matrix
      containing fluoride, chloride, bromide, nitrate, hydrogen carbonate and sulfate.
      All peaks were clearly resolved, and calibrations were linear with estimated
      3sigma detection limits of 0.83, 0.39, and 0.35 microM for hypophosphite,
      phosphite, and orthophosphate, respectively.

PMID- 15250411
TI  - Determination of residual trifluoroacetate in protein purification buffers and
      peptide preparations by ion chromatography.
AB  - Trifluoroacetate (TFA) is commonly used in a variety of pharmaceutical
      applications. Because of its toxic nature, it is important to reliably measure
      the effective removal of TFA. We developed an ion chromatography (IC) method to
      determine the concentration of residual TFA in samples found in the
      pharmaceutical industry. A high-capacity anion-exchange column was used to
      separate trace trifluoroacetate from an excess of chloride, phosphate, and other
      anions without the need for sample preparation. TFA was detected by suppressed
      conductivity. A method with four KOH eluent step changes was optimized and
      reproducibly executed using automated generation of the KOH eluent. We used this
      method to determine TFA in the following samples: a phosphate-buffered saline
      (PBS), an acetate-buffered saline containing protein, and a commercial peptide.
      The method detection limits for TFA in these samples were all less than 90 ng/ml.

PMID- 15250412
TI  - Analysis of anions in hydrofluoro ethers by ion chromatography.
AB  - Hydrofluoro ethers (HFES) are considered to be an ideal cleaning solvent in
      applications like vapor degreasing and wet cleaning. It is also a good solvent
      replacement for CFCs (chlorofluorocarbons), HCFCs (hydrochlorofluorocarbons),
      HFCs (hydrofluorocarbons) and chlorinated solvents because they have a short
      atmospheric lifetime and low global warming potential. Based upon their
      properties, hydrofluoro ethers are ideally suited for the demands of the
      electronics industry. However, the electronics industry requires these solvents
      to have high purity, especially in the area of residual anions. This paper will
      present information on an extraction methodology for the transfer of anions from
      the hydrofluoro ether to water. Then, an analytical method utilizing ion
      chromatography that is capable of detection of 10 anions (fluoride, acetate,
      formate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, and phosphate) in
      the part per billion level will be demonstrated.

PMID- 15250413
TI  - Alternative approach to enhancing cation selectivity in ion chromatography.
AB  - A new approach to enhance cation selectivity in ion chromatography (IC) is
      described. Two packings, one carrying a conventional carboxylate cation exchanger
      and the other carrying a crown ether (CE) phase are packed into two separate
      columns and used in series. The resolution between sodium and ammonium and
      between ammonium and potassium is increased significantly. The two stationary
      phases may also be mixed and packed into a single column. The selectivity of the
      cations can be adjusted easily by varying the dimensions of the carboxylate and
      CE columns (in the two-column configuration), or by changing the ratio of the
      carboxylate cation exchanger to the CE packing (in the single-column
      configuration). These new systems separate ammonium and sodium, even when the
      sodium concentration is 5000 times higher. Amines such as ethanolamine and
      triethanolamine can also be separated from the alkali and alkaline-earth cations.

PMID- 15250414
TI  - Vacancy ion-exclusion/adsorption chromatography of aliphatic amines on a
      polymethacrylate-based weakly basic anion-exchange column.
AB  - Vacancy ion-exclusion/adsorption chromatography has been applied to investigate
      the separation behavior of five aliphatic amines (ethylamine, propylamine,
      butylamine, pentylamine and hexylamine) on a polymethacrylate-based weakly basic
      anion-exchange column (Tosoh TSKgel DEAE-5PW). This system is consisted of
      analytes as a mobile phase and water as an injected sample. In the vacancy ion
      exclusion/adsorption chromatography, the elution order was as follows: ethylamine
      < propylamine < butylamine < pentylamine < hexylamine, depending on their
      hydrophobicity. The retention times of the amines were decreased with decreasing
      their concentrations in the mobile phase. The retention times and resolutions of
      the amines were increased by adding a basic compound (e.g., lithium hydroxide or
      heptylamine) and by increasing the pH of mobile phase (pH > 11). This was because
      the dissociations of amine samples in the mobile phase were suppressed and thus
      the hydrophobic adsorption effects were enhanced. The linearity of calibration
      graphs could be obtained from the peak areas of the amine samples injected to the
      0.05, 0.5 and 5 mM of amine mobile phase at pH 11 by heptylamine. The detection
      limits of aliphatic amines as injected samples were around 1 microM for five
      aliphatic amines at three different amine mobile phases. From these results, the
      retention behaviors of aliphatic amines on vacancy ion-exclusion/adsorption
      chromatography were concluded to be governed by the hydrophobic adsorption
      effect.

PMID- 15250415
TI  - Highly sensitive determination of hydrazine ion by ion-exclusion chromatography
      with ion-exchange enhancement of conductivity detection.
AB  - An ion-exclusion chromatography method with ion-exchange enhancement of
      conductivity was developed for the selective separation and sensitive
      determination of hydrazine ion from alkali/alkaline earth metal cations and
      ammonium ion. Hydrazine ion was separated by ion-exclusion/penetration effect
      from other cations on a weakly basic anion-exchange column in the OH- form
      (TSKgel DEAE-5PW). Moreover, two different ion-exchange resin columns were
      inserted between the separating column and conductimetric detector in order to
      improve the sensitivity of hydrazine ion. The first enhancement column packed
      with a strongly basic anion-exchange resin in the SO4(2-) form (TSKgel SAX) for
      hydrazine ion can convert from N2H5OH to (N2H5)2SO4. Moreover, the second
      enhancement column packed with a strongly acidic cation-change resin in the H+
      form (TSKgel SCX) can convert to H2SO4. As a result, the sensitivity of hydrazine
      ion using two conductivity enhancement columns could be 26.8-times greater than
      using the separating column alone. This method was effectiveness also for the
      enhancement of ammonium ion (6.1-times) and sodium ion (1.2-times). The
      calibration graph of hydrazine ion detected as H2SO4 was linear over the
      concentration range of 0.001-100 ppm (r2 = 0.9988). The detection limit of
      hydrazine ion in this system was 0.64 ppb. Therefore, hydrazine ion in real
      boiler water sample could be accurately determined, avoiding the interference of
      other cations.

PMID- 15250416
TI  - Determination of some aliphatic carboxylic acids in anaerobic digestion process
      waters by ion-exclusion chromatography with conductimetric detection on a weakly
      acidic cation-exchange resin column.
AB  - The determination of seven aliphatic carboxylic acids, formic, acetic, propionic,
      isobutyric, n-butyric, isovaleric and n-valeric acids in anaerobic digestion
      process waters was examined using ion-exclusion chromatography with
      conductimetric detection. The analysis of these biologically important carboxylic
      acids is necessary as a measure for evaluating and controlling the process. The
      ion-exclusion chromatography system employed consisted of polymethacrylate-based
      weakly acidic cation-exchange resin columns (TSKgel OApak-A or TSKgel Super IC
      A/C). weakly acidic eluent (benzoic acid), and conductimetric detection. Particle
      size and cation-exchange capacity were 5 microm and 0.1 meq./ml for TSKgel OApak
      A and 3 microm and 0.2 meq./ml for TSKgel Super IC-A/C, respectively. A dilute
      eluent (1.0-2.0 mM) of benzoic acid was effective for the high resolution and
      highly conductimetric detection of the carboxylic acids. The good separation of
      isobutyric and n-butyric acids was performed using the TSKgel Super IC-A/C column
      (150 mm x 6.0 mm i.d. x 2). The simple and good chromatograms were obtained by
      the optimized ion-exclusion chromatography conditions for real samples from
      mesophilic anaerobic digestors, thus the aliphatic carboxylic acids were
      successfully determined without any interferences.

PMID- 15250418
TI  - Determination of acrylamide in drinking water by large-volume direct injection
      and ion-exclusion chromatography-mass spectrometry.
AB  - Acrylamide, a known neurotoxin and putative human carcinogen, has been included
      among the substances to be monitored in drinking water according to the European
      Union Directive 98/83 on potable water. This paper reports a new method based on
      the combination of ion-exclusion chromatographic separation and MS detection.
      Samples of drinking water have been directly injected in the microbore ICE-AS1
      column and detected in the selected-ion monitoring mode by a single quadrupole
      system with electrospray ionization. Chromatographic conditions, such as eluent
      composition and flow rate, have been optimized by a central composite design
      experiment. Statistical analysis of data showed that the amount of acetonitrile
      fraction in the eluent mixture, composed by acetonitrile and formic acid
      solution, is the variable that most influences retention of the acrylamide peak.
      After optimization of MS detection parameters, this method has been validated for
      spiked drinking water samples. The effect of large-volume injection (up to 500
      microl) has been also explored. Linearity was evaluated from 0.5 to 5 microg l(
      1). Repeatability, expressed as R.S.D., was 16 and 12% at 0.5 and 1 microg l(-1)
      respectively. The limit of detection was 0.20 ppb with 500 microl injection
      volume.

PMID- 15250417
TI  - Validated ion-exclusion chromatographic method for citrate and acetate in medical
      fluids.
AB  - In this paper we describe the development and validation of a solid-phase
      extraction procedure, followed by ion-exclusion chromatographic determination of
      citrate and acetate in medical fluids. The medical fluids contained trace levels
      of non-polar compounds, which were not of interest for the purposes of assay
      requirements, but due to their strong affinity towards the ion-exclusion
      chromatography column necessitated a 180-min long runtime to elute. The developed
      SPE procedure, based on trapping the hydrophobic compounds, on a reversed-phase
      material, while allowing analytes of interest elute off unretained, shortened the
      runtime to 35 min. The procedure is simple since it has only two steps,
      conditioning of the SPE cartridge with acetonitrile and treating the sample. The
      SPE procedure followed by ion-exclusion chromatographic determination was
      successfully validated per the International Conference on Harmonization (ICH)
      guidelines in terms of specificity, accuracy as recovery versus untreated sample,
      precision, range, linearity of response, ruggedness, stability of treated
      samples, and robustness. The validation data showed that the method is specific,
      accurate, precise, rugged, and robust. The validated method has been routinely
      used in the manufacturing environment.

PMID- 15250419
TI  - Application of polymethacrylate resin as stationary phase in liquid
      chromatography with UV detection for C1-C7 aliphatic monocarboxylic acids and C1
      C7 aliphatic monoamines.
AB  - The application of unfunctionized polymethacrylate resin (TSKgel G3000PWXL) as a
      stationary phase in liquid chromatography with UV detection for C1-C7 aliphatic
      monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid,
      isovaleric acid, valeric acid, 3,3-dimethylbutyric acid, 4-methylvaleric acid,
      hexanoic acid, 2-methylhexanoic acid, 5-methylhexanoic acid and heptanoic acid)
      and C1-C7 aliphatic monoamines (methylamine, ethylamine, propylamine,
      isobutylamine, butylamine, isoamylamine, amylamine, 1,3-dimethylbutylamine,
      hexylamine, 2-heptylamine and heptylamine) was carried out. Using dilute sulfuric
      acid as the eluent, the TSKgel G3000PWXL, resin acted as an advanced stationary
      phase for these C1-C7 carboxylic acids. Excellent simultaneous separation and
      symmetrical peaks for these C1-C7 carboxylic acids were achieved on a TSKgel
      G3000PWXL column (150 mm x 6 mm i.d.) in 60 min with 0.25 mM sulfuric acid
      containing 1 mM 2-methylheptanoic acid at pH 3.3 as the eluent. Using dilute
      sodium hydroxide as the eluent, the TSKgel G3000PWXL resin also behaved as an
      advanced stationary phase for these C1-C7 amines. Excellent simultaneous
      separation and good peaks for these C1-C7 amines were achieved on the TSKgel
      G3000PWXL column in 60 min with 10 mM sodium hydroxide containing 0.5 mM 1
      methylheptylamine at pH 11.9 as the eluent.

PMID- 15250420
TI  - Separation and conductimetric detection of C1-C7 aliphatic monocarboxylic acids
      and C1-C7 aliphatic monoamines on unfunctionized polymethacrylate resin columns.
AB  - The application of unfunctionized polymethacrylate resin (TSKgel G3000PWXL) as a
      stationary phase in liquid chromatography with conductimetric detection for C1-C7
      aliphatic monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric
      acid, isovaleric acid, valeric acid, 3,3-dimethylbutyric acid, 4-methylvaleric
      acid, hexanoic acid, 2-methylhexanoic acid, 5-methylhexanoic acid and heptanoic
      acid) and C1-C7 aliphatic monoamines (methylamine, ethylamine, propylamine,
      isobutylamine, butylamine, isoamylamine, amylamine, 1,3-dimethylbutylamine,
      hexylamine, 2-heptylamine and heptylamine) was attempted with C8 aliphatic
      monocarboxylic acids (2-propylvaleric acid, 2-ethylhexanoic acid, 2
      methylheptanoic acid and octanoic acid) and C8 aliphatic monoamines (1,5
      dimethylhexylamine, 2-ethylhexylamine, 1-methylheptylamine and octylamine) as
      eluents, respectively. Using 1 mM 2-methylheptanoic acid at pH 4.0 as the eluent,
      excellent separation and relatively high sensitive detection for these C1-C7
      carboxylic acids were achieved on a TSKgel G3000PWXL column (150 mm x 6 mm i.d.)
      in 60 min. Using 2 mM octylamine at pH 11.0 as the eluent, excellent separation
      and relatively high sensitive detection for these C1-C7 amines were also achieved
      on the TSKgel G3000PWXL column in 60 min.

PMID- 15250421
TI  - Retention behavior of C1-C6 aliphatic monoamines on anion-exchange and
      polymethacrylate resins with heptylamine as eluent.
AB  - Retention behavior of C1-C6, aliphatic monoamines (methylamine, ethylamine,
      propylamine, butylamine, amylamine and hexylamine) on columns (150 mm x 6 mm
      i.d.) packed with various anion-exchange resins (styrene-divinylbenzene (PS-DVB)
      copolymer-based strongly basic anion-exchange resin: TSKgel SAX, polymethacrylate
      based strongly basic anion-exchange resin: TSKgel SuperQ-5PW and polymethacrylate
      based weakly basic anion-exchange resin: TSKgel DEAE-5PW) and unfunctionized
      polymethacrylate resins (TSKgel G5000PW and TSKgel G3000PWXL) was investigated
      with basic solutions (sodium hydroxide and heptylamine) as the eluents. Due to
      strongly electrostatic repulsion (ion-exclusion effect) between these anion
      exchange resins and these amines, peak resolution between these amines on these
      anion-exchange resin columns was unsatisfactory with both sodium hydroxide and
      heptylamine as the eluents. In contrast, these polymethacrylate resins were
      successfully applied as the stationary phases for the separation of these C1-C6
      amines with heptylamine as eluent, because of both small hydrophobicity and small
      cation-exchange ability of these resins. Excellent simultaneous separation,
      highly sensitive conductimetric detection and symmetrical peaks for these C1-C6
      amines were achieved on the TSKgel G3000PWXL column in 35 min with 5 mM
      heptylamine at pH 11.1 as the eluent.

PMID- 15250422
TI  - Use of coupled open-tubular capillaries for in-line ion-exchange preconcentration
      of anions by capillary electrochromatography with elution by a transient
      isotachophoretic gradient.
AB  - Open-tubular capillaries have been joined together for use in on-column ion
      exchange preconcentration of anions by capillary electrochromatography (CEC) with
      elution by a transient isotachophoretic gradient. This involved the coupling of a
      preconcentration capillary and a separation capillary using a PTFE sleeve. Such
      coupling allowed precise lengths of differently coated capillaries to be joined
      in-line to form a single multi-mode column. The different segments could be
      tailored to optimize a separation by either altering the length of each segment
      to precisely manipulate the amount of stationary phase present or by changing the
      internal diameter of each segment to alter the phase ratio in the chromatographic
      column without affecting the path length for UV detection. In this work, a
      segmented in-line capillary was used in conjunction with a fluoride
      octanesulfonate discontinuous electrolyte system to increase the number of anions
      that could be preconcentrated and separated. Quaternary ammonium functionalised
      latex particles were used for creating the preconcentration segment and the
      separation segment was coated with poly(diallyldimethylammonium chloride). This
      allowed the detection of trace anions in drinking water and in situ sampling of
      river water for the analysis of trace inorganic anions. The repeatability of
      producing the quaternary ammonium functionalized latex-coated segments was
      assessed and the effect of segmentation on peak efficiency was investigated.

PMID- 15250423
TI  - Poly(tetrafluoroethylene) separation capillaries for capillary electrophoresis.
      Properties and applications.
AB  - Poly(tetrafluoroethylene) (PTFE) is a material widely known for its inertness and
      excellent electrical properties. It is also transparent in the UV region and has
      a reasonable thermal conductivity. These properties make PTFE a suitable material
      for the separation capillary in capillary electrophoresis. Differences in the
      chemistry of the capillary wall compared to fused silica (FS) can make PTFE an
      interesting alternative to FS for some special applications. In this work,
      properties of a commercial PTFE capillary of approx. 100 microm i.d. were
      investigated, including the dependence of electroosmotic flow (EOF) on pH for
      unmodified and dynamically modified PTFE, optical properties, and practical
      aspects of use. The main problems encountered for the particular PTFE capillary
      used in this study were that it was mechanically too soft for routine usage and
      the crystallinity of the PTFE caused light scattering, leading to high background
      absorbance values in the low UV region. The profile of the EOF versus pH for bare
      PTFE surprisingly showed significantly negative EOF values at pH < 4.2, with an
      EOF of -30 x 10(-9) m2 V(-1) s(-1) being observed at pH 2.5. This is likely to be
      caused by either impurities or additives of basic character in the PTFE, so that
      after their protonation at acidic pH they establish a positive charge on the
      capillary wall and create a negative EOF. A stable cationic semi-permanent
      coating of poly(diallyldimethylammonium chloride) (PDDAC) could be established on
      the PTFE capillary and led to very similar magnitudes of EOF to those observed
      with FS. A hexadecanesulfonate coating produced a cathodic EOF of extremely high
      magnitude ranging between +90 and +110 x 10(-9) m2 s(-1) V(-1), which are values
      high enough to allow counter-EOF separation of high mobility inorganic anions. In
      addition, pH-independent micellar electrokinetic capillary chromatography (MEKC)
      separations could be easily realised due to hydrophobic adsorption of sodium
      dodecylsulfate (used to form the micelles) on the wall of the PTFE capillary. The
      use of polymers that would be mechanically more robust and optically transparent
      in the low-UV region should make such CE capillaries an interesting alternative
      to fused silica.

PMID- 15250424
TI  - Speciation of arsenic and selenium by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) with direct UV detection, both on-capillary and
      with a high-sensitivity detection cell (HSDC), were used for the simultaneous
      determination of arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid
      (MMA), dimethylarsinic acid (DMA), selenate [Se(VI)], selenite [Se(IV)],
      selenocystine (SeC), selenomethionine (SeM) and selenocystamine (SeCM). These
      anionic and cationic species were separated with negative separation voltage
      polarity in a capillary coated with poly(diallydimethylammonium chloride)
      (PDDAC). The background electrolyte (BGE) providing optimal separation was 15 mM
      phosphate buffer at pH 10.6. Arsenic and selenium species were detected at 195
      and 200 nm, respectively. The limit of detection (LOD) values with on-capillary
      detection (75 microm i.d.) for the individual analytes were 1.02, 1.50, 1.08,
      1.35, 19.5, 0.36, 0.32, 1.11 and 1.47 mg/L, respectively (expressed as arsenic or
      selenium). The method precision for peak area was from 2.1 to 3.4% relative
      standard deviation. HSDC was applied to increase the detection sensitivity and
      gave LOD improvement factors from 4.7 to 8.2, yielding LODs for the individual
      target analytes ranging from 0.049 to 2.38 mg/L. When the normal sample stacking
      mode was employed using a sample plug up to 4.6% of capillary volume, both the
      cationic and anionic analytes were stacked simultaneously with LOD improvement
      factors of 2.6-4.5 yielding LODs for the individual analytes ranging from 0.11 to
      7.42 mg/L. The method was applied for the speciation of arsenic in sediment and
      determination of SeM in a selenium nutrition supplement. The achieved separation
      selectivity also gives the method a more general application potential for
      simultaneous arsenic and selenium speciation when hyphenated with inductively
      coupled plasma MS.

PMID- 15250425
TI  - Analysis of benzyldimethyldodecylammonium bromide in chemical disinfectants by
      liquid chromatography and capillary electrophoresis.
AB  - Two novel analytical methodologies using capillary electrophoresis (CE) and high
      performance liquid chromatography (HPLC) were developed and compared for the
      determination of benzyldimethyldodecylammonium bromide (BAB) in commercial
      compound chemical disinfectants. The LC analysis was performed with a Kromasil
      C18 (200 mm x 4.6 mm, 5 microm) column and a mobile phase of A:B = 80:20 (A:
      acetonitrile, B: 4 mmol/L octanesulfonic sodium--0.02 mol/L acetic sodium,
      adjusted with acetic acid to pH 5.2) at a flow rate of 1.0 mL/min. Detection was
      by ultraviolet absorption at 262 nm. The CE analysis was performed in a bare
      fused-silica capillary with 75 microm i.d. and total length of 46.4 cm with a
      buffer solution of 50% acetonitrile -50 mmol/L NaH2PO4, pH 2.24. The applied
      voltage was 20 kV. Detection was by ultraviolet absorption at 214 nm. Under
      optimized conditions, the HPLC retention time and CE migration time for BAB was
      9.18 and 5.08 min, respectively. Calibration curves of peak area versus
      concentration gave correlation coefficients of 0.9996 for HPLC and 0.9994 for CE.
      The detection limits for HPLC and CE were 1.6 mg/L and 0.2 mg/L, respectively.
      Average recoveries at three concentration levels (50, 100, 200 mg/L for HPLC: 20,
      40, 100 mg/L for CE) were 99.94 +/- 1.5, 99.64 +/- 1.3 and 99.61 +/- 0.4% for
      HPLC and 120.47 +/- 2.6, 102.06 +/- 8.7 and 103.05 +/- 3.0% for CE, respectively.
      Although both methods were shown to be suitable for the determination of BAB in
      commercial disinfectant compounds, CE provided analysis with less solvent
      purchase/disposal and better column efficiency, whereas HPLC provided superior
      precision.

PMID- 15250426
TI  - Analysis of hydroxide, inorganic sulphur species and organic anions in kraft
      pulping liquors by capillary electrophoresis.
AB  - A new method has been developed for the determination of hydroxide, sulphide,
      thiosulphate, sulphate, sulphite, chloride, oxalate and formate in kraft green,
      white and black liquors by capillary electrophoresis. The method provides
      baseline resolution of all analytes of interest using an electrolyte composed of
      10 mM sodium chromate and 2 mM tetradecyltrimethylammonium hydroxide. Separations
      are conducted under constant current conditions at 25 degrees C and analytes are
      quantified by indirect UV-detection at 275 nm. A brief, post run wash of the
      capillary with 0.5 M NaOH and water gave improved inter- and intra-run
      repeatability of both migration times and peak areas. Sulphide and other
      oxysulphur species were relatively stable in white and green liquors diluted in
      helium-sparged water. However, sulphide present in black liquor samples diluted
      in the same solvent underwent rapid oxidation to form sulphite and thiosulphate.
      thereby precluding the measurement of all three anions. We discovered that
      quinone-type compounds present in black liquor catalyze the oxidation of sulphide
      and that the addition of reduced glutathione at a concentration of I mg/mL during
      black liquor dilution completely stabilized sulphide, sulphite and thiosulphate
      for at least one hour, thus allowing for quantitative analysis of the analytes. A
      mechanism is proposed to explain the action of both quinones and that of
      glutathione. Results obtained by the new method compared well with those obtained
      by ion chromatography, titrimetry, and from spike-recovery experiments.

PMID- 15250427
TI  - Capillary electrophoresis of organic cations at high salt concentrations.
AB  - At concentrations of 100 mM or higher the chemical nature of both the cation and
      anion in the background electrolyte (BGE) can be varied to manipulate the
      migration times of protonated aniline cations. Significant differences were noted
      with Li+, Na+ and K+ for capillary electrophoretic runs carried out at pH 3.
      However, much greater differences in migration times were observed at acidic pH
      values when the BGE contained protonated cations of aliphatic amines. Analyte
      migration became progressively slower in the series: methylamine, diethylamine,
      diethylamino ethanol and triethylamine. A major part of this effect was
      attributed to an opposing electroosmotic flow (EOF) resulting from a positively
      charged coating of the capillary surface with the amine cations in the BGE via a
      dynamic equilibrium. The amine cations also interact in solution with the analyte
      ions to reduce their electrophoretic mobilities. Migration times of anilines
      could be varied systematically over a broad range according to the BGE amine
      cation selected. Excellent separations of seven closely-related anilines were
      obtained with the new system.

PMID- 15250428
TI  - Inclusion, exclusion, or diagnosis?

PMID- 15250429
TI  - Clinical neurophysiology and quantitative sensory testing in the investigation of
      orofacial pain and sensory function.
AB  - Chronic orofacial pain represents a diagnostic and treatment challenge for the
      clinician. Some conditions, such as atypical facial pain, still lack proper
      diagnostic criteria, and their etiology is not known. The recent development of
      neurophysiological methods and quantitative sensory testing for the examination
      of the trigeminal somatosensory system offers several tools for diagnostic and
      etiological investigation of orofacial pain. This review presents some of these
      techniques and the results of their application in studies on orofacial pain and
      sensory dysfunction. Clinical neurophysiological investigation has greater
      diagnostic accuracy and sensitivity than clinical examination in the detection of
      the neurogenic abnormalities of either peripheral or central origin that may
      underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological
      testing may also reveal trigeminal pathology when magnetic resonance imaging has
      failed to detect it, so these methods should be considered complementary to each
      other in the investigation of orofacial pain patients. The blink reflex, corneal
      reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the
      recording of trigeminal somatosensory-evoked potentials with near-nerve
      stimulation have all proved to be sensitive and reliable in the detection of
      dysfunction of the myelinated sensory fibers of the trigeminal nerve or its
      central connections within the brainstem. With appropriately small thermodes,
      thermal quantitative sensory testing is useful for the detection of trigeminal
      small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most
      sensitive to lesions causing axonal injury. By combining different techniques for
      investigation of the trigeminal system, an accurate topographical diagnosis and
      profile of sensory fiber pathology can be determined. Neurophysiological and
      quantitative sensory tests have already highlighted some similarities among
      various orofacial pain conditions and have shown heterogeneity within clinical
      diagnostic categories. With the aid of neurophysiological recordings and
      quantitative sensory testing, it is possible to approach a mechanism-based
      classification of orofacial pain.

PMID- 15250430
TI  - Joint tenderness, jaw opening, chewing velocity, and bite force in patients with
      temporomandibular joint pain and matched healthy control subjects.
AB  - AIMS: To evaluate the effect of temporomandibular arthralgia on mandibular
      mobility, chewing, and bite force. METHODS: Twenty female patients (ages 19 to 45
      years) with unilateral temporomandibular joint (TMJ) pain during chewing (49 +/-
      27 mm on a 100-mm visual analog scale) and provocation, as well as TMJ
      tenderness, were studied. The TMJ conditions were classified as disc derangement
      disorders (n = 9), osteoarthritis (n = 7), and inflammatory disorders (n = 4).
      The patients were compared with matched healthy volunteers without orofacial pain
      or tenderness. Exclusion criteria were the presence of fewer than 24 teeth or
      malocclusion. The methods used were (1) algometric assessment of the pressure
      pain threshold (PPT) over the TMJ; (2) clinical recordings of maximum jaw
      opening; (3) computerized kinematic assessment of maximum vertical distance,
      velocity, and cycle duration during chewing of soft gum; and (4) measurement of
      unilateral molar bite force. RESULTS: The mean (+/- SD) PPT in the patients'
      painful side (69 +/- 20 kPa; P = .000001) was significantly lower than in the
      control subjects (107 +/- 22 kPa). Jaw opening was also significantly less (P =
      .00003) in the patients (42 +/- 9 mm) than in the controls (52 +/- 4 mm). Chewing
      cycle duration and maximum closing velocity were significantly different (P < or
      = .03) in the patients (948 +/- 185 milliseconds and 142 +/- 46 mm/s,
      respectively) versus the controls (765 +/- 102 milliseconds and 173 +/- 43 mm/s,
      respectively), and bite force was significantly lower (P = .000003) in the
      patients (238 +/- 99 N) than in the controls (394 +/- 80 N). Both bite force and
      jaw opening in patients were significantly correlated (P < or = .02) with PPT (r
      = 0.53 and 0.63, respectively). CONCLUSION: These systematic findings supplement
      results from acute pain experiments and confirm indications from unspecified
      patient groups that the clinical presence of long-standing TMJ pain is associated
      with marked functional impairment. This impairment might be a result of reflex
      adaptation and long-term hypoactivity of the jaw muscles.

PMID- 15250431
TI  - The additional value of a home physical therapy regimen versus patient education
      only for the treatment of myofascial pain of the jaw muscles: short-term results
      of a randomized clinical trial.
AB  - AIMS: To compare the short-term efficacy of patient education only versus the
      combination of patient education and home exercises for the treatment of
      myofascial pain of the jaw muscles. MATERIALS AND METHODS: Seventy myogenous
      temporomandibular disorder patients were assigned to 2 treatment groups. One
      group received patient education supplemented by general information about self
      care of the jaw musculature. The other group received both education and a home
      physical therapy program. Treatment contrast, calculated from the mean normalized
      relative changes in anamnestic and clinical scores, was used to determine
      treatment success. Clinical outcome measures included pressure pain threshold
      (PPT) of the masseter, anterior temporalis, and Achilles tendon; pain-free
      maximal jaw opening; and pain on chewing, spontaneous muscle pain, and headache
      as rated on visual analog scales. RESULTS: After 3 months the success rate was
      57% for the group that received education only and 77% for the group that
      received both education and home physical therapy (P = .157). The patients were
      then redivided into 2 groups: successfully treated patients and unsuccessfully
      treated patients. In the unsuccessfully treated group, pain-free maximal jaw
      opening increased significantly more among those who had been in the education
      and physical therapy group than among those who had been in the education-only
      group (P = .019). The change in PPT was significantly greater in successfully
      treated patients than in unsuccessfully treated patients (.009 < P < .039),
      independent of the treatment modality, with higher PPTs among successful
      patients. There were no significant differences between the successfully and
      unsuccessfully treated groups or between treatment modalities for any other
      variable. CONCLUSION: Over a period of 3 months, the combination of education and
      a home physical therapy regimen, as used in this protocol, is slightly more
      clinically effective than education alone for the treatment of myofascial pain of
      the jaw muscles.

PMID- 15250432
TI  - An 8-year follow-up study of temporomandibular disorder and psychosomatic
      symptoms from adolescence to young adulthood.
AB  - AIMS: To assess the prevalence of subjective symptoms of pain and/or
      temporomandibular disorder (TMD) dysfunction and their association with
      psychosomatic (PS) symptoms in a longitudinal follow-up study of Finnish young
      adults over an 8-year period. METHODS: One hundred twenty-eight Finnish young
      adults (60 men and 68 women) were assessed longitudinally at the ages of 15, 18,
      and 23 years using routine stomatognathic methods and a standardized
      questionnaire. RESULTS: The prevalence of reported TMD symptoms ranged from 6% to
      12% for pain symptoms, from 12% to 28% for dysfunctional symptoms, and from 4% to
      7% for a combination of these 2 types of symptoms. The prevalence of PS symptoms,
      which were constantly present in many of the patients who reported them, ranged
      from 7% to 11%. A significant correlation (P < .05) was found between TMD pain
      and PS symptoms at the ages of 15 and 18 years. PS symptoms were not
      significantly correlated to TMD dysfunction symptoms or to experiencing no
      symptoms at any age. The majority of subjects in all age groups with both TMD and
      PS symptoms were female, in a ratio of approximately 2 to 1. CONCLUSION: The
      prevalence of TMD and PS symptoms was low in adolescence and young adulthood, and
      there was a significant association, although relatively weak, between PS
      symptoms and reports of either TMD pain or a combination of TMD pain and
      dysfunction symptoms.

PMID- 15250433
TI  - Venlafaxine in the treatment of atypical facial pain: a randomized controlled
      trial.
AB  - AIMS: To study in a randomized placebo-controlled design the efficacy of the
      antidepressant venlafaxine, a serotonin and a weak noradrenaline reuptake
      inhibitor, in the treatment of atypical facial pain (AFP). METHODS: The study was
      a randomized, double-blind, crossover comparison of venlafaxine and a placebo. It
      consisted of 2 treatment periods, each of 4 weeks' duration, separated by a 2
      week washout period. Thirty patients suffering from chronic pain who had been
      diagnosed with AFP after a thorough clinical examination were recruited. Pain
      intensity and pain relief were registered at 6 visits. Anxiety, depression, and
      adverse effects were recorded. Venous blood samples were collected at the end of
      each treatment period for the determination of serum levels of venlafaxine and
      its metabolites. RESULTS: Twenty patients completed the trial. Eight patients
      discontinued because of adverse effects and 2 patients were excluded because of
      noncompliance. Two patients completed the trial but were excluded from the
      analysis because they experienced no pain at the baseline visit. There was no
      significant difference in pain intensity reduction between the maximum tolerated
      dose of venlafaxine (75 mg in most cases) and the placebo. Pain relief was
      significantly greater with venlafaxine than with the placebo treatment.
      Significantly more escape medication was consumed during the placebo period
      compared with the venlafaxine period. No significant correlation was found
      between the serum concentration of the drug and the response to treatment.
      Anxiety and depression scores did not differ between venlafaxine and placebo
      treatment. Adverse effects were equally common during both treatments.
      CONCLUSION: Venlafaxine was only modestly effective in the treatment of AFP.

PMID- 15250434
TI  - A comparative study between clinical and instrumental methods for the recognition
      of internal derangements with a clicking sound on condylar movement.
AB  - AIMS: To compare the results of 3 methods of recognizing internal derangements
      with a clicking sound on condylar movement: 2 function-based methods (clinical
      examination and condylar movement recording) and 1 anatomy-based method (magnetic
      resonance imaging [MRI]). METHODS: For the recognition of an anterior or
      posterior disc displacement with reduction and of hypermobility within the
      temporomandibular joint (TMJ), 42 participants underwent a clinical examination,
      an opto-electronic movement recording, and an MRI scan. The examinations were
      executed in a single-blind design, with different experienced examiners for each
      technique. In addition, for 10 randomly chosen participants, the condylar
      movement recordings and the MRI scans were carried out twice. Without the
      examiners' knowledge, these second recordings were added to the other data.
      RESULTS: Intraobserver reliability for the recognition of internal derangements
      was excellent for condylar movement recording (kappa = 0.86) and fair to good for
      MRI (kappa = 0.73). Intermethod agreement was fair to good (kappa = 0.59) between
      the 2 function-based techniques. However, intermethod agreement between the
      anatomy-based MRI technique and either of the 2 function-based techniques was
      poor (for condylar movement recording, kappa = 0.15; and for clinical
      examination, kappa = 0.12). CONCLUSION: There is a great discrepancy between the
      diagnoses for internal derangements based upon anatomical TMJ characteristics and
      those based on functional TMJ characteristics. For a function-based diagnosis,
      there is probably no need for the sophisticated technique of condylar movement
      recording, since that method shows fair to good agreement with a carefully
      performed clinical examination.

PMID- 15250435
TI  - The relationship between morphological changes of the condyle and condylar
      position in the glenoid fossa.
AB  - AIMS: To investigate whether condylar morphological changes influence the condyle
      position in the glenoid fossa as well as the amount of condylar movement from the
      intercuspal position (IP) to the reference position (RP). METHODS: Helical
      computed tomography was used for precise measurement of the joint spaces at IP
      and RP in 22 subjects (mean age 22.7 years). Subjects were divided into 2 groups,
      those without condylar bone changes (n = 11) and those with condylar bone changes
      (n = 11). The latter group was further subdivided into a flattening subgroup and
      an osteophyte subgroup, according to the type of condylar bone change. RESULTS:
      There were no significant differences in the width of the anterosuperior or
      posterosuperior joint spaces at IP between either the 2 groups or the 2
      subgroups. On the other hand, during condylar movement from IP to RP, the
      condyles moved significantly more superiorly and posterosuperiorly in the bone
      change group than in the no-bone-change group. There was also greater absolute
      horizontal condylar movement between IP and RP in the bone-change group. In
      addition, within the bone-change group, the type of condylar bone change
      influenced the amount of condylar movement. Joints with osteophyte formation
      showed the most superior, posterosuperior, and absolute horizontal movement from
      IP to RP. CONCLUSION: The findings that condyles of the bone-change group,
      especially those with osteophyte formation, were located significantly more
      anteroinferiorly in the glenoid fossa at IP than RP than the condyles of the no
      bone-change group suggest that condylar IP-RP positional changes might be related
      to condylar shape alteration.

PMID- 15250436
TI  - What Islam needs is a pope.

PMID- 15250437
TI  - Oesphageal squamous cell carcinoma in South Africa--an urgent need for improved
      efforts at screening and prevention.

PMID- 15250438
TI  - Cervical cancer screening leapfrog with human papilloma-virus testing.

PMID- 15250439
TI  - Disseminated tuberculous osteitis.

PMID- 15250440
TI  - Job's syndrome.

PMID- 15250442
TI  - [Kruisiging beswaar. ].

PMID- 15250441
TI  - On the rewards of dedication and commitment.

PMID- 15250443
TI  - Conned again?

PMID- 15250444
TI  - The one that got away!

PMID- 15250445
TI  - Community service six years on...

PMID- 15250446
TI  - Doctors v. government--who cares most?

PMID- 15250447
TI  - Addiction--starting to stop with a first step.

PMID- 15250448
TI  - Plan to battle AIDS worldwide is falling short.

PMID- 15250449
TI  - Dried blood-spot test monitors HIV treatment.

PMID- 15250450
TI  - HAART for hospital health care workers--an innovative programme.

PMID- 15250451
TI  - Insulin allergy.

PMID- 15250452
TI  - Maternal deaths--need for improved obstetric care in the Transkei region.

PMID- 15250453
TI  - Less frequent Pap smears for low-risk women?

PMID- 15250454
TI  - Symptom control in palliative care: essential for quality of life.

PMID- 15250455
TI  - Increase in trimethoprim-sulphamethoxazole (co-trimoxazole) resistance at Chris
      Hani Baragwanath Hospital, Soweto, in the AIDS era.

PMID- 15250456
TI  - Unnoticed decline in the number of unnatural deaths in South Africa.

PMID- 15250457
TI  - Treatment of uncomplicated falciparum malaria in non-immune and semi-immune
      individuals exceeding 65 kg body weight.

PMID- 15250458
TI  - Use of sedation to relieve refractory symptoms in dying patients.
AB  - OBJECTIVES: To document the use of sedation for refractory symptoms in patients
      admitted to an independent palliative care unit. METHOD: A prospective
      descriptive study. SETTING: The 7-bed inpatient unit at Sungardens Hospice,
      Pretoria. SUBJECTS: Patients who required sedation for refractory symptoms in
      addition to normal palliative care treatment between January and June 2002.
      FINDINGS: Twenty of 100 consecutive patients admitted required sedation. All had
      advanced cancer. Their mean age was 68 years. Thirty-six per cent were men and
      64% women. INDICATIONS: Agitated delirium was the most common reason (45%) for
      using sedation, followed by intractable vomiting due to inoperable malignant
      intestinal obstruction in 25% of patients. Three patients with persistent
      convulsions or myoclonic jerking and 2 patients with severe refractory dyspnoea
      required some sedation. Intractable pain was the main reason for sedation in only
      1 patient. SURVIVAL: Mean survival following the start of sedation was 92
      hours/3.8 days (range 6 - 369 hours/0.25 - 19.4 days). The combined mean survival
      recorded in 9 other studies was 57 hours/2.4 days (range 36 - 93.6 hours/1.5 -
      3.9 days). MEDICATION: The main drugs used for sedation were midazolam and
      haloperidol. The mean dosage for midazolam was 18.5 mg/24 hours (range 7.5 - 40
      mg) and for haloperidol 8 mg/24 hours (range 5 - 10 mg). For pain relief the mean
      daily dose of parenteral morphine was 76 mg (range 15 - 260 mg). CONCLUSION: Use
      of sedation for the relief of refractory symptoms at Sungardens Hospice is in
      line with several studies reported in the international literature.

PMID- 15250459
TI  - Symptoms and sites of pain experienced by AIDS patients.
AB  - INTRODUCTION: HIV/AIDS is the top single cause of mortality burden in South
      Africa and patients with AIDS present with unique and challenging symptoms and
      pain syndromes. OBJECTIVE: To identify and increase awareness of the 10 most
      prevalent symptoms and 5 most common sites of pain in patients with advanced
      AIDS. DESIGN AND SUBJECTS: A nurse-led questionnaire was used to collect data,
      and a descriptive, quantitative analysis was done. Subjects included 103 adult
      patients with World Health Organisation (WHO) stage 4 AIDS. Patients with
      impaired cognitive function were excluded. OUTCOME MEASURES: The main outcome
      measures included a list of 30 symptoms, 13 site-specific pains, age, gender,
      worst overall symptom and access to antiretroviral therapy (ART). Results were
      based on review of data collected between May 2002 and February 2003. RESULTS:
      Results showed the mean age of patients to be 35.4 years, with females an average
      of 4.4 years younger than males. There were a higher number of female respondents
      (62.6%) than males (37.4%). The 10 most common symptoms in order of prevalence
      were pain (98%), weight loss (81%), loss of appetite (70.9%), low mood (69.9%),
      weakness (66%), dry skin (56.3%), diarrhoea (53.4%), nausea and vomiting (44.7%),
      cough (44.7%) and fatigue (42.7%). Of the of respondents 34.4% mentioned pain as
      the worst overall symptom. The average number of pains experienced was 2.91.
      Females reported significantly more anxiety, genital sores and pain than males.
      Of the patients 3.9% had had access to ART. Lower limb pain was the most
      prevalent pain (66%) followed by mouth pain (50.5%), headache (42.3%), throat
      pain (39.8%) and chest pain (17.5%). CONCLUSIONS: Patients with advanced AIDS in
      South Africa suffer significantly from pain and many distressing symptoms. In the
      light of the HIV/AIDS pandemic in South Africa reforms are needed to increase
      knowledge and education in the palliative management of AIDS.

PMID- 15250460
TI  - Physician education programme improves quality of diabetes care.
AB  - BACKGROUND: Diabetes mellitus is a common chronic disease needing long-term
      glycaemic control to prevent complications. Guidelines are available for
      achievement of optimal glycaemic control, but these are seldom properly
      instituted. OBJECTIVES: To determine if a physician education programme and a
      structured consultation schedule would improve the quality of diabetes patient
      care in a diabetes clinic. SETTING: Two tertiary care diabetes clinics at
      Kalafong Hospital, Pretoria. STUDY DESIGN: Quasi-experimental controlled before
      and-after study. METHODS: A baseline audit of the quality of care in two
      comparable diabetes clinics was performed. Three hundred patients were randomly
      selected for audit of their hospital records: 141 from the intervention and 159
      from the control clinics. Thereafter a physician training programme and a
      structured consultation schedule were introduced to the intervention clinic and
      maintained for a 1-year period. The control clinic continued with care as usual.
      Process and outcome measures were determined at a post-intervention audit and
      compared between the two groups. Consultation time was measured for both the
      intervention and control groups and data were compared. RESULTS: At baseline the
      intervention and control groups did not differ significantly with regard to
      process and outcome measures. After intervention the intervention group had
      significantly higher process measure scores than the control group (p < 0.01).
      HbA1c did not significantly differ between the two groups (p = 0.60). The average
      number of clinic visits reduced over time for the intervention group compared
      with the control group (p < 0.01), but the average consultation times were
      significantly longer (p < 0.01). CONCLUSION: The introduction of a physician
      education programme and a structured consultation schedule improved the quality
      of care delivered at a tertiary care diabetes clinic.

PMID- 15250461
TI  - X-linked hypophosphataemia in South Africa.
AB  - OBJECTIVES: To investigate the pattern of clinical presentation in a series of
      South African subjects with X-linked hypophosphataemia (XLH) with particular
      reference to ethnic differences in presentation and inheritance, and to determine
      the perceptions and psychosocial problems associated with the disease. DESIGN AND
      SETTING: The clinical details of 50 subjects were collected from their records as
      well as from examining those currently attending the clinics held at Chris Hani
      Baragwanath Hospital and the National Health Laboratory Services in Johannesburg.
      There were 17 males and 33 females in the study. The psychosocial part of the
      study involved interviews with 20 parents and 7 subjects (aged 16 years or more).
      RESULTS: Thirty-one of the subjects were black, 17 white and 2 Indian. The mean
      age of clinical onset was 2.02 years (range 0.25 - 10 years). Fifty-four per cent
      of the cases were apparently sporadic. The prevalence of sporadic mutations was
      64% among the black subjects and 41% among the white subjects. No differences
      were found in either clinical or biochemical presentation between genders or
      ethnic groups, despite an apparently higher sporadic presentation in the black
      children. The study also showed that this disorder had not only affected family
      life but also the lives of the subjects and their interpersonal relationships.
      The hereditary nature of the condition was not clear to most parents even after
      having attended the clinic for many years. CONCLUSIONS: South African subjects
      with XLH have similar features to those reported in other studies but there is a
      higher prevalence of sporadic mutations in the black subjects. Better counselling
      services are needed to improve the understanding of this condition among parents
      of affected children.

PMID- 15250462
TI  - The frequency of Toxocara infection in mental retarded children.
AB  - Human toxocariasis is commonly seen in places where stray and Toxocara canis
      infected dog population is high. There is a strong correlation between frequency
      of Toxocara infection, life style, and infection risk. Institutionalization of
      mental retarded patients increases to risk of toxocariasis. In this study, we
      aimed at investigating the frequency of Toxocara infection among children with
      mental retardation not requiring institutionalization. The study included 96
      cases, who had educatable mental retardation and 85 healthy subjects who
      comprised the control group. Anti-Toxocara IgG or IgM antibodies were
      investigated in all serum samples, using ELISA method. The frequency of Toxocara
      infection was found significantly higher in mental retarded cases than in those
      in the control group (18.8% and 7.1% respectively) (p < 0.05). There was no
      significant difference between mental retarded children and the control group in
      terms of mean age, age groups, gender, owning dogs and cats and duration of their
      ownership, socio-economic level and behavioural factors, and personal hygiene (p
      > 0.05). We did not find any significant difference between Toxocara seropositive
      and seronegative mental retarded children in terms of demographic factors and
      epidemiological factors that could increase the risk of Toxocara infection (p >
      0.05). The present study is the first seroprevalence study carried out with a
      mental retarded group not requiring institutionalization. Determination of high
      frequency of Toxocara infection suggests that these subjects constitute a risk
      factor for Toxocara infection, which may be attributed to their behavioural
      patterns.

PMID- 15250463
TI  - First record of Lutzomyia evansi (Nunez-Tovar 1924) in Mexico (Diptera:
      Psychodidae, Phlebotominae).
AB  - The phlebotomine sand fly Lutzomyia evansi is recorded in Mexico for the first
      time. This species is a suspected vector of Leishmania infantum in other parts of
      its geographical range and was captured in a focus of American visceral
      leishmaniasis where the principal vector, Lu. longipalpis sensu lato, was also
      found. The relative public health importance of the two species in the study area
      (Chiapas state, Southern Mexico) is discussed.

PMID- 15250464
TI  - Phenotypic plasticity in adult worms of Schistosoma mansoni
      (Trematoda:Schistosomatidae) evidenced by brightfield and confocal laser scanning
      microscopies.
AB  - A comparative morphometric study was performed to identify host-induced
      morphological alterations in Schistosoma mansoni adult worms. A wild parasite
      population was obtained from a naturally infected rodent (Nectomys squamipes) and
      then recovered from laboratory infected C3H/He mice. Furthermore, allopatric worm
      populations maintained for long-term under laboratory conditions in Swiss Webster
      mice were passed on to N. squamipes. Suckers and genital system (testicular
      lobes, uterine egg, and egg spine) were analyzed by a digital system for image
      analysis. Confocal laser scanning microscopy (CLSM) showed details of the genital
      system (testicular lobes, vitelline glands, and ovary) and the tegument just
      below the ventral sucker. Significant morphological changes (p < 0.05) were
      detected in male worms in all experimental conditions, with no significant
      variability as assessed by CLSM. Significant changes (p < 0.05) were evident in
      females from the wild population related to their ovaries and vitelline glands,
      whereas allopatric females presented differences only in this last character. We
      conclude that S. mansoni worms present the phenotypic plasticity induced by
      modifications in the parasite's microenvironment, mainly during the first passage
      under laboratory conditions.

PMID- 15250465
TI  - Feeding sources and natural infection of Belminus herreri (Hemiptera, Reduviidae,
      Triatominae) from dwellings in Cesar, Colombia.
AB  - Belminus herreri, originally described from specimens collected in Panama, was
      considered entirely silvatic until to 2000 when it was found for the first time
      in a domestic habitat in Colombia. In 2001, during a new search of houses in the
      Department of Cesar, Colombia, 121 specimens were collected. Study of their
      feeding sources using an ELISA test revealed that 96% of these specimens had fed
      on cockroaches (Blattidae). However, a small proportion of these B. herreri
      specimens also showed the presence of Trypanosoma cruzi in their gut contents,
      suggesting a possible role for these insects in the epidemiology of Chagas
      disease.

PMID- 15250466
TI  - Effects of tetrodotoxin and ion replacements on the short-circuit current induced
      by Escherichia coli heat stable enterotoxin across small intestine of the gerbil
      (Gerbillus cheesmani).
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 jejuna and ilea taken from fed, starved (4
      days, water ad lib) and undernourished (50% control food intake for 21 days)
      gerbil (Gerbillus cheesmani) were investigated. The effect of neurotoxin
      tetrodotoxin (TTX 10 microM) and the effects of replacing chloride by gluconate
      or the effects of removing bicarbonate from bathing buffers on the maximum
      increase in Isc induced by STa were also investigated. The maximum increase in
      Isc which resulted from the addition of STa were significantly higher in jejuna
      and ilea taken from starved and undernourished gerbils when compared with the fed
      control both using stripped and unstripped sheets. In the two regions of the
      small intestine taken from fed and starved animals TTX reduced the maximum
      increase in Isc induced by STa across unstripped sheets only. Moreover in jejuna
      and ilea taken from undernourished gerbils TTX reduced significantly the maximum
      increase in Isc induced by STa across stripped and unstripped sheets. Replacing
      chloride by gluconate decreased the maximum increase in Isc induced by STa across
      jejuna and ilea taken from undernourished gerbils only. Removing bicarbonates
      from bathing buffer decreased the maximum increase in Isc across the jejuna and
      ilea taken from starved and undernourished gerbils.

PMID- 15250467
TI  - Genetic variability analysis among clinical Candida spp. isolates using random
      amplified polymorphic DNA.
AB  - The patterns of genetic variation of samples of Candida spp. isolated from
      patients infected with human immunodeficiency virus in Vitoria, state of Espirito
      Santo, Brazil, were examined. Thirty-seven strains were isolated from different
      anatomical sites obtained from different infection episodes of 11 patients
      infected with the human immunodeficiency virus (HIV). These samples were
      subjected to randomly amplified polymorphic DNA (RAPD) analysis using 9 different
      primers. Reproducible and complex DNA banding patterns were obtained. The
      experiments indicated evidence of dynamic process of yeast colonization in HIV
      infected patients, and also that certain primers are efficient in the
      identification of species of the Candida genus. Thus, we conclude that RAPD
      analysis may be useful in providing genotypic characters for Candida species
      typing in epidemiological investigations, and also for the rapid identification
      of pathogenic fungi.

PMID- 15250468
TI  - Analysis of the first and second internal transcribed spacer sequences of the
      ribosomal DNA in Biomphalaria tenagophila complex (Mollusca: Planorbidae).
AB  - The first and second internal transcribed spacer regions (ITS1 and ITS2) of the
      ribosomal DNA of Biomphalaria tenagophila complex (B. tenagophila, B.
      occidentalis, and B. t. guaibensis) were sequenced and compared. The alignment
      lengths of these regions were about 655 bp and 481 bp, respectively. Phylogenetic
      relationships among the Biomphalaria species were inferred by Maximum Parsimony
      and Neighbor-joining methods. The phylogenetic trees produced, in most of the
      cases, were in accordance with morphological systematics and other molecular data
      previously obtained by polymerase chain reaction and restriction fragment length
      polymorphism analysis. The present results provide support for the proposal that
      B. tenagophila represents a complex comprising B. tenagophila, B. occidentalis
      and B. t. guaibensis.

PMID- 15250469
TI  - Abnormal expression of CD54 in mixed reactions of mononuclear cells from hyper
      IgE syndrome patients.
AB  - Hyper-IgE syndrome (HIES) is a rare multisystem disorder characterized by
      increased susceptibility to infections associated with heterogeneous immunologic
      and non-immunologic abnormalities. Most patients consistently exhibit defective
      antigen-induced-T cell activation, that could be partly due to altered
      costimulation involving accessory molecules; however, the expression of these
      molecules has never been documented in HIES. Therefore, we investigated the
      expression of CD11a, CD28, CD40, CD54, CD80, CD86, and CD154 in peripheral blood
      mononuclear cells from six patients and six healthy controls by flow cytometry
      after autologous and mixed allogeneic reactions. Only the allogeneic stimuli
      induced significant proliferative responses and interleukin 2 and interferon
      gamma production in both groups. Most accessory, molecules showed similar
      expression between patients and controls with the exception of CD54, being
      expressed at lower levels in HIES patients regardless of the type of stimulus
      used. Decreased expression of CD54 could partly explain the deficient T cell
      activation to specific recall antigens in HIES patients, and might be responsible
      for their higher susceptibility to infections with defined types of
      microorganisms.

PMID- 15250470
TI  - Effect of angiotensin II and losartan on the phagocytic activity of peritoneal
      macrophages from Balb/C mice.
AB  - Angiotensin II (AII), a product of rennin-angiotensin system, exerts an important
      role on the function of immune system cells. In this study, the effect of AII on
      the phagocytic activity of mouse peritoneal macrophages was assessed. Mice
      peritoneal macrophages were cultured for 48 h and the influence of different
      concentrations of AII (10(-14) to 10(-7) M) and/or losartan, 10(-16) to 10(-6)
      M), an AT1 angiotensin receptor antagonist, on phagocytic activity and superoxide
      anion production was determined. Dimethylthiazoldiphenyltetrazolium bromide
      reduction and the nucleic acid content were used to assess the cvtotoxicity of
      losartan. A stimulatory effect on phagocytic activity (P < 0.05) was observed
      with 10(-13) M and 10(-12 M) AII concentrations. The addition of losartan (up
      to10(-14) M) to the cell cultures blocked (P < 0.001) the phagocytosis indicating
      the involvement of AT1 receptors. In contrast, superoxide anion production was
      not affected by AII or losartan. The existence of AT1 and AT2 receptors in
      peritoneal macrophages was demonstrated by immunofluorescence microscopy. These
      results support the hypothesis that AII receptors can modulate murine macrophage
      activity and phagocytosis, and suggest that AII may have a therapeutic role as an
      immunomodulatory agent in modifying the host resistance to infection.

PMID- 15250471
TI  - A contribution to the diagnosis of Capillaria hepatica infection by indirect
      immunofluorescence test.
AB  - A highly specific pattern of immunofluorescence was noted when sera from
      Capillaria hepatica-infected rats were tested against the homologous worms and
      eggs present either in paraffin or cryostat sections from mouse liver. The
      pattern was represented by a combined apple green fluorescence of the internal
      contents of worms and eggs, which persisted in serum-dilutions of 1:400 up to
      1:1600. Unequivocal fluorescent pattern was observed from 15 days up to 3 months
      following inoculation of rats with embryonated C. hepatica eggs and such result
      was confirmed by the ELISA. After the 4th month of infection, the indirect
      immunofluorescence test turned negative, probably revealing the extinction of
      parasitism, however the ELISA was contradictory, disclosing high levels of
      antibodies in this period. The IIF was also negative when control normal rat sera
      and sera from rats administered by gavage with immature C. hepatica eggs
      (spurious infection), or for reactions made against Schistosoma mansoni eggs,
      although a weakly positive pattern occurred with Fasciola hepatica eggs. The
      indirect immunofluorescence test may be recommended for use with human sera to
      detect early C. hepatica infection in special clinical instances and in
      epidemiological surveys, since it is a simple, inexpensive, and reliable test,
      presenting excellent sensitivity and specificity. Although the diagnosis is
      positive only during early infection, this is the period when the symptoms are
      usually more severe and the need for differential diagnosis is greater.

PMID- 15250472
TI  - Stage-specific activity of potential antimalarial compounds measured in vitro by
      flow cytometry in comparison to optical microscopy and hypoxanthine uptake.
AB  - The evaluation of new antimalarial agents using older methods of monitoring
      sensitivity to antimalarial drugs are laborious and poorly suited to discriminate
      stage-specific activity. We used flow cytometry to study the effect of
      established antimalarial compounds, cysteine protease inhibitors, and a quinolone
      against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites
      were treated for 48 h with different drug concentrations and the parasitemia was
      determined by flow cytometry methods after DNA staining with propidium iodide. P.
      falciparum erythrocytic life cycle stages were readily distinguished by flow
      cytometry. Activities of established and new antimalarial compounds measured by
      flow cytometry were equivalent to results obtained with microscopy and metabolite
      uptake assays. The antimalarial activity of all compounds was higher against P.
      falciparum trophozoite stages. Advantages of flow cytometry analysis over
      traditional assays included higher throughput for data collection, insight into
      the stage-specificity of antimalarial activity avoiding use of radioactive
      isotopes.

PMID- 15250473
TI  - Detection of Toxoplasma gondii DNA by polymerase chain reaction in experimentally
      desiccated tissues.
AB  - Despite toxoplasmosis being a common infection among human and other warm-blooded
      animals worldwide, there are no findings about Toxoplasma gondii evolutionary
      forms in ancient populations. The molecular techniques used for amplification of
      genetic material have allowed recovery of ancient DNA (aDNA) from parasites
      contained in mummified tissues. The application of polymerase chain reaction
      (PCR) to paleoparasitological toxoplasmosis research becomes a promising option,
      since it might allow diagnosis, acquisition of paleoepidemiological data, access
      to toxoplasmosis information related origin, evolution, and distribution among
      the ancient populations. Furthermore, it makes possible the analysis of parasite
      aDNA aiming at phylogenetic studies. To standardize and evaluate PCR
      applicability to toxoplasmosis paleodiagnostic, an experimental mummification
      protocol was tested using desiccated tissues from mice infected with the ME49
      strain cysts, the chronic infection group (CIG), or infected with tachyzoites (RH
      strain), the acute infection group (AIG). Tissues were subjected to DNA
      extraction followed by PCR amplification of T. gondii B1 gene. PCR recovered T.
      gondii DNA in thigh muscle, encephalon, heart, and lung samples. AIG presented
      PCR positivity in encephalon, lungs, hearts, and livers. Based on this results,
      we propose this molecular approach for toxoplasmosis research in past
      populations.

PMID- 15250474
TI  - Immunoblotting for the serodiagnosis of Helicobacter pylori infection in
      Brazilian patients with and without gastric carcinoma.
AB  - We evaluated the performance of a commercial immunoblotting in the serodiagnosis
      of Helicobacter pylori infection in Brazilian patients. The presence of anti-H.
      pylori antibodies was also investigated in a group of 20 duodenal ulcer patients
      after successful treatment. One hundred and ninety one patients were studied.
      Among the 164 infected patients, 46 had gastric carcinoma. The duodenal ulcer
      patients were treated with antimicrobial drugs and the eradication of the
      microorganism was confirmed in all of them one month after the end of the
      treatment by the 13C-urea breath test. Sera were assayed for H. pylori antibodies
      using the Helicoblot 2.0 (Genelabs Diagnostics, Singapore). The sensitivity,
      specificity, positive, and negative predictive values of the test were 93.9%,
      92.6%, 98.7%, and 71.4%, respectively. The sensitivity of the test was similar in
      patients with (93.5%) and without (95.7%) gastric carcinoma. Twenty-four months
      after the end of the treatment, the band of 116 kDa was still detected in one of
      the patients. In conclusion, the Helicoblot 2.0 is an accurate test to diagnose
      H. pylori infection and although it can not be employed to monitor the bacterium
      eradication, it may be useful for diagnosing past infection, especially in
      gastric carcinoma patients.

PMID- 15250475
TI  - Comparison between splenic and lymph node aspirations as sampling methods for the
      parasitological detection of Leishmania chagasi infection in dogs.
AB  - The sensitivities of spleen and lymph node cultures for the diagnosis of canine
      visceral leishmaniasis were compared in 64 anti-Leishmania antibody positive dogs
      from an endemic area in Brazil. The sensitivity of spleen cultures for Leishmania
      detection was 97.9%; in lymph node cultures it was 25%. Positive spleen culture
      was more frequent (p = 0.048, Fisher's exact probability test) in symptomatic (28
      out of 33 animals) than in asymptomatic animals (19 out of 31 animals). These
      results support the use of spleen instead of lymph node aspiration as the choice
      method for the parasitological diagnosis of the infection.

PMID- 15250476
TI  - Aedes aegypti resistance to temephos during 2001 in several municipalities in the
      states of Rio de Janeiro, Sergipe, and Alagoas, Brazil.
AB  - For more than 30 years temephos, an organophosphate insecticide, has been the
      sole larvicide used in Brazil in the control of Aedes aegypti. Organophosphates
      were also used for adult control, being replaced by pyrethroids since 1999. In
      this same year the Brazilian Health Foundation started the coordination of the
      Ae. aegypti Insecticide Resistance Monitoring Program. In the context of this
      program, our group was responsible for the detection of temephos resistance in a
      total of 12 municipalities in the states of Rio de Janeiro (RJ), Alagoas (AL),
      and Sergipe (SE) during 2001. In each municipality, a pool of mosquitoes
      collected from different districts was used, with the exception of Rio de Janeiro
      city, where eight districts have been separately evaluated. Exposure of larvae to
      the diagnostic dose of temephos revealed resistance in all localities examined,
      with mortality levels ranging from 4% (Pilares district, Rio de Janeiro, RJ) to
      61.9% (Campos dos Goytacazes, RJ). Quantification of mortality showed resistance
      ratios from 6.1 (Aracaju, SE) to 16.8 (Sao Goncalo, RJ and Penha district, Rio de
      Janeiro, RJ). The national dengue control program is presently using these data
      to subside insecticide resistance management.

PMID- 15250477
TI  - Molluscicidal effect of nicotinanilide and its intermediate compounds against a
      freshwater snail Lymnaea luteola, the vector of animal schistosomiasis.
AB  - The molluscicidal effect of nicotinanilide was evaluated and compared with
      niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against
      different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature,
      young mature, and adults. Calculated values of lethal concentrations (LC50 and
      LC90) showed that both nicotinanilide and niclosamide as toxic against eggs,
      immature, and adults. The young mature stage of the snails was comparatively more
      tolerant to both molluscicides than the other stages. The toxicity of the
      intermediate compounds of nicotinanilide against the young mature stage of the
      snails showed them as ineffective. The mortality pattern of the snails exposed to
      LC90 concentration of these molluscicides showed niclosamide to kill faster
      (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies
      it may be concluded that both molluscicides are toxic against all the stages of
      the L. luteola snails.

PMID- 15250478
TI  - Activity of oil-formulated Beauveria bassiana against Triatoma sordida in
      peridomestic areas in Central Brazil.
AB  - Field tests were carried out during the rainy season of 2001/2002 in Sao Luis de
      Montes Belos, Goias, Brazil, to evaluate the potential of the entomopathogenic
      fungus, Beauveria bassiana, against peridomestic Triatoma sordida. An oil-water
      formulation of the isolate CG 14 (Embrapa) was applied in triatomine infested hen
      houses of four farms at a final concentration of 10(6) conidia/cm2. Numbers of T.
      sordida decreased over the next 25 days, after application of the fungus, and B.
      bassiana developed on dead insects in one hen house. A high number of B. bassiana
      colonies was detected in substrates collected in treated hen houses 24 h after
      application of CG 14. In the following three months the presence of B. bassiana
      declined to values found before treatment.

PMID- 15250479
TI  - Evaluation of cholinesterase level in an endemic population exposed to malathion
      suspension formulation as a vector control measure.
AB  - The manuscript describes a study on the blood cholinesterase (ChE) level in an
      exposed population at different interval of time after spraying with malathion
      suspension (SRES) use for kala-azar vector control in an endemic area of Bihar,
      India. The toxicity of a 5% malathion formulation in the form of a slow release
      emulsified suspension (SRES) was assessed by measuring serum ChE levels in
      spraymen and in the exposed population. The study showed a significant decrease
      in ChE levels in the spraymen (p < 0.01) after one week of spraying and in
      exposed population one week and one month after of spraying (p < 0.01), but was
      still within the normal range of ChE concentration, one year after spraying, the
      ChE concentration in the exposed population was the same as prior to spraying (p
      > 0.01). On no occasion was the decrease in ChE level alarming. A parallel
      examination of the clinical status also showed the absence of any over toxicity
      or any behavioural changes in the exposed population. Hence, it may be concluded
      that 5% malathion slow release formulation, SRES, is a safe insecticide for use
      as a vector control measure in endemic areas of kala-azar in Bihar, India so long
      as good personal protection for spraymen is provided to minimize absorption and
      it can substitute the presently used traditional DDT spray.

PMID- 15250480
TI  - Ivermectin resistant and susceptible third-stage larvae of Haemonchus contortus:
      cholinesterase and phosphatase activities.
AB  - Cholinesterase and acid phosphatase (AP), but not alkaline phosphatase
      activities, were detected in cytosolic and membrane-bound fractions of ivermectin
      resistant and susceptible Haemonchus contortus infective-stage larvae. Some
      differences in acetylcholinesterase activity of cytosolic fractions and in the AP
      activity of these fractions as well as in the response to AP inhibitors by
      membrane-bound fractions were detected. Data are discussed.

PMID- 15250481
TI  - Trypanocidal activity of Meliaceae and Rutaceae plant extracts.
AB  - The in vitro trypanocidal activity of 22 extracts and 43 fractions of plants
      belonging to the families Meliaceae and Rutaceae was evaluated. The extracts from
      leaves of Conchocarphus heterophyllus and branches of Trichilia ramalhoi were the
      most active. The trypanocidal activity seems to be increased by fractionation of
      the extracts. Fractions from C. heterophyllus and Galipea carinata were the most
      active and a 100% lysis of the parasites was observed for five fractions. From
      one of them were isolated two flavonoids: flavone and 7-methoxyflavone, which
      showed weak trypanocidal activity. The results obtained from the extracts and
      fractions revealed that the order Rutales is a promising source for the search of
      new drugs for Chagas disease. Phytochemical studies with the other active
      fractions are underway in order to isolate compounds, which could be associated
      with observed activities.

PMID- 15250482
TI  - In vitro activity of Etanidazole against the protozoan parasite Trypanosoma
      cruzi.
AB  - We investigated the in vitro action of an hydrosoluble 2-nitroimidazole,
      Etanidazole (EZL), against Trypanosoma cruzi, the etiologic agent of Chagas
      disease. EZL displayed lethal activity against isolated trypomastigotes as well
      as amastigotes of T. cruzi (RA strain) growing in Vero cells or J774 macrophages,
      without affecting host cell viability. Although not completely equivalent to
      Benznidazole (BZL), the reference drug for Chagas chemotherapy, EZL takes
      advantage in exerting its anti-T. cruzi activity for longer periods without
      serious toxic side effects, as those recorded in BZL-treated patients. Our
      present results encourage further experiments to study in depth the trypanocidal
      properties of this drug already licensed for use in human cancers.

PMID- 15250483
TI  - Radioligand-binding methods for membrane preparations and intact cells.
AB  - The radioligand-binding assay is a relatively simple but powerful tool for
      studying G-protein-coupled receptors. There are three basic types of radioligand
      binding experiments: (1) saturation experiments from which the affinity of the
      radioligand for the receptor and the binding site density can be determined; (2)
      inhibition experiments from which the affinity of a competing, unlabeled compound
      for the receptor can be determined: and (3) kinetic experiments from which the
      forward and reverse rate constants for radioligand binding can be determined.
      Detailed methods for typical radioligand-binding assays for G-protein-coupled
      receptors in membranes and intact cells are presented for these types of
      experiments. Detailed procedures for analysis of the data obtained from these
      experiments are also given.

PMID- 15250484
TI  - Determination of allosteric interactions using radioligand-binding techniques.
AB  - Methods are presented for identifying and quantifying allosteric interactions of
      G-protein-coupled receptors with labeled and unlabeled ligands using radioligand
      binding assays. The experimental designs and analyses are based on the simplest
      ternary complex allosteric model.

PMID- 15250485
TI  - Generation, use, and validation of receptor-selective antibodies.
AB  - Antibodies have proved invaluable in the study of G-protein-coupled receptors
      (GPCRs). The utility of these immunoglobulin probes for investigation of protein
      structures and functions arises from their selectivity as well as their
      versatility. Antibodies can be used to analyze GPCR size, abundance,
      distribution, turnover, modification, interaction with other proteins, and
      functional properties. In this chapter, techniques for the generation and
      characterization of receptor-selective antibodies are described. Two protocols
      are given for the generation of antibodies: (1) development of polyclonal
      antibodies (PAbs) against synthetic peptides corresponding to a specific site
      within a GPCR and (2) selection of synthetic single-chain fragment variable
      (scFv) monoclonal antibodies (MAbs) from libraries expressed on the surface of
      bacteriophage. Immunoblot and enzyme-linked immunosorbent assays for
      characterization of the selectivity and affinity of such antibodies are
      described. Finally, methods are given for improvement of the titer and
      specificity of PAbs.

PMID- 15250486
TI  - Immunocytochemical identification of G-protein-coupled receptor expression and
      localization.
AB  - Immunocytochemistry exploits the incomparable specificity of the antibody-antigen
      interaction to form the basis of a flexible approach to the study of expression
      and localization of proteins both in model systems and their physiological
      context. This chapter details the theory and practice of the technique as well as
      lists the materials required. A general protocol is proposed, which can be
      adapted to suit the needs of individual investigators using the suggestions
      outlined in the Notes. The use of frozen tissue sections and cultured cells is
      described. Finally, the most common causes for failure of the technique are
      presented, along with likely solutions.

PMID- 15250487
TI  - Generation and use of epitope-tagged receptors.
AB  - Epitope tagging of a receptor involves introducing a defined amino acid sequence,
      to which an antibody has already been produced, into the primary amino acid
      sequence of the receptor. The new sequence can be as short as 10-15 amino acids
      and the method allows the receptor to be monitored without having to raise an
      antibody specific to it, and so permits its biochemical characterization and
      immunolocalization within cells. Other related techniques involve the
      introduction of functional domains of proteins such as green fluorescence protein
      or one of its derivatives into receptors to allow their direct visualization.
      There are a wide range of amino acid tag sequences, and fluorescent proteins,
      available for use as tags, and choice of tag will depend on several factors
      including the availability of antisera and cost. The position for the
      introduction of the tag into the native receptor will depend on precisely what
      the requirements of the experiments are but it must always be such that the
      receptor is normally processed, trafficked, and remains functional after tagging.
      These considerations are discussed fully in this chapter, which also describes
      examples of strategies for introducing tags, and some general methods for use in
      the characterization of the tagged proteins.

PMID- 15250488
TI  - Identification of G-protein-coupled receptor mRNA expression by Northern blotting
      and in situ hybridization.
AB  - G-protein-coupled receptor mRNAs are expressed at low levels and therefore
      present a challenge for the study of their sites and levels of expression. In
      situ hybridization (ISH) and Northern blotting are powerful methods for the
      localization of mRNAs and the study of regulation of mRNA expression. ISH
      combines the power of precise cellular localization with the ability to perform
      semiquantitative analysis of the mRNA level, whereas Northern blotting has the
      ability to identify genetic splice variants, or to study multiple RNA molecules
      sequentially in the same tissue samples. These protocols give step-by-step
      instructions for the performance of these techniques, and the analysis of the
      data that can be obtained using them.

PMID- 15250489
TI  - Electron microscopic studies of receptor localization.
AB  - The localization and density of G-protein-coupled receptors (GPCRs) on the cell
      surface is a critical factor for specifying signaling within and between neurons.
      GPCRs and their associated signaling components are localized to specific
      neuronal compartments that give rise to a variety of functional implications.
      Therefore, information regarding the precise localization of GPCRs is a
      prerequisite for studies designed to elucidate their contribution to neuronal
      function, and can be achieved only by immunoelectron microscopy. Three main
      techniques for immunoelectron microscopy exist: the preembedding
      immunoperoxidase, the preembedding immunogold, and the postembedding immunogold
      techniques. The preembedding immunogold method is reliable for the localization
      of receptors at extrasynaptic and perisynaptic sites. The preembedding
      immunoperoxidase method provides valuable information on regional distribution of
      receptors. Finally, to localize any receptor at synaptic sites the only reliable
      method is the postembedding immunogold technique. Therefore, the three
      immunocytochemical methods provide complementary information about the cellular,
      subcellular, and subsynaptic location of any receptor.

PMID- 15250490
TI  - Generation of model cell lines expressing recombinant G-protein-coupled
      receptors.
AB  - The molecular cloning of the cDNA sequences encoding most G-protein-coupled
      receptors, including those from humans, allows their study in a variety of
      recombinant systems. In this respect, transfected mammalian cell lines constitute
      the most frequently used model for investigating the pharmacological and
      biochemical properties of these receptors. Several protocols have been described
      (based on the use of calcium phosphate precipitation, DEAE dextran, cationic
      lipids, and electroporation), allowing their transient or stable expression in
      diverse cell lines. This chapter gives a brief overview of the different
      techniques and provides methodology for the generation of transiently transfected
      cells and for selection, isolation and maintenance of stable transfected cell
      lines.

PMID- 15250491
TI  - Viral infection protocols.
AB  - This chapter describes the protocol for preparation of recombinant adenoviruses
      and infection of target cells to express transiently G-protein-coupled receptors
      or other proteins of interest. Adenoviruses are nonenveloped viruses containing a
      linear double-stranded DNA genome. Their life cycle does not normally involve
      integration into the host genome, rather they replicate as episomal elements in
      the nucleus of the host cell and consequently there is no risk of insertional
      mutagenesis. The wild-type adenovirus genome is approx 35 kb, of which up to 30
      kb can be replaced by foreign DNA. Adenoviral vectors are very efficient at
      transducing the gene of interest in target cells in vitro and in vivo and can be
      produced at high titers (>10(11)/mL). The viral infection has a number of useful
      features: (1) the efficiency of gene transduction is very high (up to 100% in
      sensitive cells). (2) The infection is easy and does not alter physically the
      cell membrane for gene transduction. (3) It is possible to infect cells that are
      resistant to transfection with plasmids (including nondividing cells).

PMID- 15250492
TI  - Expression of G-protein signaling components in adult mammalian neurons by
      microinjection.
AB  - Although methods for expressing foreign proteins in clonal cell lines are well
      established, mature neurons remain a difficult preparation for the introduction
      of foreign genes. Microinjection is a reliable method for producing robust
      targeted expression in neurons that has advantages over conventional
      transfection/infection methodologies. Here, I describe procedures for expressing
      signaling proteins in adult rat sympathetic neurons by direct microinjection of
      cRNA and cDNA into the cytoplasm and nucleus, respectively. The methods are
      applicable to a wide variety of peripheral and central neuron preparations, as
      well as clonal cell lines.

PMID- 15250493
TI  - Covalent modification of G-proteins by affinity labeling.
AB  - The activation of heterotrimeric G-proteins is tightly regulated by the exchange
      of GTP for GDP in the alpha-subunit; mostly--but not exclusively--seven
      transmembrane receptors function as the guanine nucleotide exchange factors
      (GEFs). A research goal may be to determine which G-protein alpha-subunit is
      activated by the receptor under investigation. In a membrane preparation obtained
      from cells or tissues this can be achieved in a seemingly straightforward manner
      by determining if the receptor increases the covalent incorporation of GTP
      analogs into G-protein alpha-subunits. Because the GTP analogs may be labeled to
      high specific radioactivity the alpha-subunit can then be identified with the use
      of specific antibodies. One of the compounds we present here (2',3'-dialdehyde
      GTP) can also be employed to block receptor-mediated G-protein activation and to
      disrupt the cognate signaling pathway.

PMID- 15250494
TI  - Measurement of agonist-stimulated [35S]GTPgammaS binding to assess total G
      protein and Galpha-subtype-specific activation by G-protein-coupled receptors.
AB  - On activation, G-protein-coupled receptors (GPCRs) exert many of their cellular
      actions through promotion of guanine nucleotide exchange on the Galpha-subunit of
      heterotrimeric G-proteins to release free Galpha-GTP and betagamma-subunits. In
      membrane preparations, GTP can be substituted by 35S-labeled guanosine 5'-O-(3
      thio)triphosphate ([35S]GTPgammaS) and on agonist stimulation a stable
      [35S]GTPgammaS-Galpha complex will form and accumulate. Separation of 35S-bound
      GTPgammaS-Galpha complexes from free [35S]GTPgammaS allows differences between
      basal and agonist-stimulated rates of [35S]GTPgammaS-Galpha complex formation to
      be used to obtain pharmacological information on receptor-G-protein information
      transfer. Further, by releasing Galpha-subunits into solution following the
      [35S]GTPgammaS binding step, Galpha-subunit-specific antibodies can be used to
      investigate the Galpha-protein subpopulations activated by receptors by
      immunoprecipitation of [35S]GTPgammaS-Galpha complexes and quantification by
      scintillation counting. Here we describe a total [35S]GTPgammaS binding assay and
      a modification of this method that incorporates a Galpha-specific
      immunoprecipitation step.

PMID- 15250495
TI  - Identification and quantitation of G-protein alpha-subunits.
AB  - The demonstration that many intracellular signaling processes are mediated by a
      family of closely related guanine nucleotide binding proteins (G-proteins) has
      led to the development of specific techniques that can be used to identify which
      of these polypeptide(s) is involved on receptor activation by ligand. In
      addition, these methods can be used to probe the specificity of the interaction
      and to yield information about the stoichiometries involved.

PMID- 15250496
TI  - Analysis of function of receptor-G-protein and receptor-RGS fusion proteins.
AB  - Fusion constructs between G-protein-coupled receptors and G-protein alpha
      subunits have been used to examine a variety of aspects of the functioning of
      these signaling systems. Here we describe some of the various techniques and
      methods used in detail. The process of fusing the two components, the receptor
      and the G-protein alpha-subunit, result in a construct that acts as an agonist
      stimulated GTPase enzyme whose expression level can be accurately determined by
      radioligand binding. The effects of different ligands, mutations, and other
      signaling system components can thus be analyzed by a series of relatively simple
      assays. Recently we have begun to supplement this approach with the use of
      fusions between G-protein-coupled receptors and regulator of G-protein signaling
      proteins to examine the function of this important group of signaling molecules.

PMID- 15250497
TI  - Assessment of receptor internalization and recycling.
AB  - Internalization of G-protein-coupled receptors (GPCRs) occurs in response to
      agonist activation of the receptors and causes a redistribution of receptors away
      from the plasma membrane toward endosomes. Internalization of lower-affinity
      small molecule GPCRs such as muscarinic acetylcholine and adrenergic receptors
      has been measured using hydrophilic antagonist radioligands that are membrane
      impermeant. In contrast, internalization of peptide hormone receptors is assessed
      by measuring the internalization of a radiolabeled- or fluorescently labeled
      peptide hormone. More recently, the use of epitope-tagged receptors has allowed
      the measurement of changes in receptor subcellular distribution by the use of
      immunoassay and immunofluorescence confocal microscopy. This chapter describes
      each of these approaches to the measurement of receptor internalization and
      describes the advantages and disadvantages of each method.

PMID- 15250498
TI  - G-protein-coupled receptor phosphorylation and palmitoylation.
AB  - It is now clear that nearly all G-protein-coupled receptors (GPCRs) are
      phosphorylated and palmitolyated. The process of receptor phosphorylation has
      been extensively studied because it offers a regulatory mechanism that is both
      rapid and dynamic. However, it has recently become clear that palmitoyaltion of
      GPCRs at C-terminal cysteine residues may also offer dynamic receptor
      modification. A growing number of GPCRs have been demonstrated to undergo rapid
      agonist-mediated changes in their palmitoylation status with functional
      implications to receptor signaling. This chapter aims to outline the methods we
      have used to investigate agonist-mediated changes in GPCR phosphorylation and
      palmitoylation.

PMID- 15250500
TI  - Ubiquitination of G-protein-coupled receptors.
AB  - In this chapter we describe methods for detecting the ubiquitination state of G
      protein-coupled receptors (GPCRs). This involves coexpression of a GPCR with an
      epitope-tagged ubiquitin construct in a heterologous expression system.
      Modification by ubiquitin of the GPCR resulting from agonist activation is
      detected by immunoprecipation and subsequent immunoblotting for the epitope
      tagged ubiquitin. We use here the chemokine receptor CXCR4 as the model receptor;
      however, this could be easily modified to detect the ubiquitination state of any
      GPCR.

PMID- 15250499
TI  - Identification of G-protein-coupled receptor phosphorylation sites by 2D
      phosphopeptide mapping.
AB  - Reversible phosphorylation is important for G-protein-coupled receptor (GPCR)
      signaling, desensitization, and endocytosis, yet the precise location and role of
      in vivo phosphorylation sites is unknown for most receptors. This chapter
      describes a powerful analytical method for the direct identification of GPCR
      phosphorylation sites by two-dimensional (2D) phosphopeptide mapping. The GPCR of
      interest is isolated from 32P-labeled cells by immunoprecipitation and
      transferred to nitrocellulose membranes. In situ cleavage by trypsin releases
      phosphopeptides that are separated by a combination of high-voltage
      electrophoresis and chromatography. Phosphoamino acid analysis and Edman
      sequencing of isolated phosphopeptides reveals information that can lead to the
      direct identification of GPCR phosphorylation sites. Furthermore, the 2D
      phosphopeptide mapping technique allows the analysis of temporal and positional
      changes in the GPCR phosphorylation pattern under different physiological
      conditions.

PMID- 15250501
TI  - Receptor mutagenesis strategies for examination of structure-function
      relationships.
AB  - This chapter describes three different strategies of receptor mutagenesis with
      their advantages, disadvantages, and limitations. Oligonucleotide-directed
      mutagenesis using either the Altered Sites II in vitro mutagenesis system or the
      GeneTailor site-directed mutagenesis system can generate base
      substitutions/deletions/insertions that yield single/multiple amino acid
      substitutions/deletions/insertions and/or N- or C-terminal truncations in GPCRs.
      Polymerase chain reaction-based mutagenesis strategies allow
      substitutions/deletions/insertions of larger domains within GPCRs, creating
      truncated receptors or receptor chimeras. In addition, some guidelines are given
      and examples are provided to facilitate design and interpretation of mutational
      experiments.

PMID- 15250502
TI  - Study of G-protein-coupled receptor-protein interactions by bioluminescence
      resonance energy transfer.
AB  - Complex networks of protein-protein interactions are key determinants of cellular
      function, including those regulated by G-protein-coupled receptors (GPCRs).
      Formation of either stable or transitory complexes are involved in regulating all
      aspects of receptor function, from ligand binding through to signal transduction,
      desensitization, resensitization and downregulation. Today, 50% of all recently
      launched drugs are targeted against GPCRs. This particular class of proteins is
      extremely useful as a drug target because the receptors are partly located
      outside the cell, simplifying bioavailability and delivery of drugs directed
      against them. However, being located within the cell membrane causes difficulties
      for the study of GPCR function and bioluminescence resonance energy transfer
      (BRET), a naturally occurring phenomenon, represents a newly emerging, powerful
      tool with which to investigate and monitor dynamic interactions involving this
      receptor class. BRET is a noninvasive, highly sensitive technique, performed as a
      simple homogeneous assay. involving the proximity-dependent transfer of energy
      from an energy donor to acceptor resulting in the emission of light. This
      technology has several advantages over alternative approaches as the detection
      occurs within live cells, in real time, and is not restricted to a particular
      cellular compartment. The use of such biophysical techniques as BRET, will not
      only increase our understanding of the nature of GPCR regulation and the protein
      complexes involved, but could also potentially lead to the development of novel
      therapeutics that modulate these interactions.

PMID- 15250503
TI  - Fluorescence resonance energy transfer to study receptor dimerization in living
      cells.
AB  - The versatility, sensitivity, and feasibility of fluorescence methods are very
      attractive to study protein-protein interaction at low levels of protein
      expression. However, one of the most severe limits in protein chemistry has been
      the difficulty of introducing site-specific fluorescent labels. The development
      of genetically encoded fluorescent probes, that is, green fluorescent protein
      (GFP) and its variants therefore opened up a broad field of novel applications.
      To characterize protein-protein interactions and determine detailed spatio
      temporal dynamics of partners that are molecularly well characterized,
      fluorescence energy transfer methods are excellent nondestructive tools in living
      cells. Cellular responses to external factors are extensively based on direct
      molecular interaction and especially G-protein-coupled receptors (GPCRs) have
      been shown to interact with an unexpected level of complexity. Classical models
      of signal transduction describe GPCRs as monomeric proteins, while recent studies
      using fluorescence resonance energy transfer (FRET) and other methods show that
      GPCRs can also function as homo- or heterodimers. Theoretical background
      information on FRET technology and its diverse applications are summarized here.
      A detailed description of a spectroscopic method for FRET studies in the field of
      GPCR interaction is presented to facilitate and propagate studies to increase our
      understanding of protein-protein interactions involving GPCRs.

PMID- 15250504
TI  - Identification of protein interactions by yeast two-hybrid screening and
      coimmunoprecipitation.
AB  - Many protein interactions with G-protein-coupled receptors (GPCRs) appear to
      influence receptor signaling and functional regulation. There is great interest
      therefore in methods for the identification of novel or unanticipated GPCR
      binding proteins. A proven method for identifying such protein interactions is
      the yeast two-hybrid screen, which involves screening the protein products of a
      cDNA library with a selected domain derived from a GPCR. Once it is established
      that a candidate protein produces a specific positive interaction within the
      yeast two-hybrid system, it is important to demonstrate further that this
      interaction is likely to occur in vivo. Coimmunoprecipitation, in which proteins
      of interest are copurified with the receptor under study, is a good way to
      address this important issue. Together, the yeast two-hybrid screen and
      coimmunoprecipitation are a useful way to identify and sort through candidate
      GPCR-interacting proteins prior to analysis in physiological studies.

PMID- 15250505
TI  - Study of G-protein-coupled receptor-protein interactions using gel overlay assays
      and glutathione-S-transferase-fusion protein pull-downs.
AB  - Numerous recent studies have suggested that the predicted cytosolic domains of G
      protein-coupled receptors (GPCRs) represent a surface for association with
      proteins that may serve multiple roles in receptor localization, turnover, and
      signaling beyond the well-characterized interactions of these receptors with
      heterotrimeric G-proteins. This chapter describes two in vitro methods for
      ascertaining interactions between GPCRs and various binding partners: gel overlay
      strategies and GST-fusion protein pull-downs.

PMID- 15250506
TI  - Receptor knock-out and knock-in strategies.
AB  - Accumulating examples have demonstrated that knock-out and knock-in mice of G
      protein-coupled receptors (GPCRs) are useful in elucidating physiological
      functions of the receptor in vivo. GPCR knock-out and knock-in are achieved by
      either (1) manipulation of the endogenous locus of the receptor gene or (2)
      transgenic expression of the modified receptor. Historically speaking, the first
      generation knock-outs made the best use of homologous recombination in embryonic
      stem (ES) cells and their totipotency to introduce the desired mutation into the
      endogenous receptor locus. In the second-generation knock-outs using the Cre/loxP
      system, the disruption of the receptor gene is cell-type specific or region
      specific but is irreversible in principle. In contrast, transgenic expression in
      the receptor knock-out mice of the wild-type receptor protein under a tissue- and
      stage-specific promoter (conditional "rescue" of the receptor knock-out) can be
      easily applied to create "reversible" or "inducible" knock-out of the receptor.
      This is called the third generation knock-out. In the following sections, we
      introduce examples of the materials and methods based on our in vivo analyses of
      the metabotropic glutamate receptor-subtype 1 (mGluR1).

PMID- 15250508
TI  - Of vaccination and infectious diseases in 2003.

PMID- 15250507
TI  - Statistical methods in G-protein-coupled receptor research.
AB  - In this chapter we provide an introduction to statistical methods appropriate in
      G-protein-coupled receptor research, including examples. Topics covered include
      the choice of appropriate averages and measures of dispersion to summarize data
      sets, and the choice of tests of significance, including t-tests and one- and two
      way analysis of variance (ANOVA) plus posttests for normally distributed
      (Gaussian) data and their nonparametric equivalents. Techniques for transforming
      non-normally distributed data to more Gaussian distributions are discussed.
      Concepts of statistical power, errors, and the use of these in determining the
      optimal size of experiments are considered. Statistical aspects of linear and
      nonlinear regression are discussed, including tests for goodness-of-fit to the
      chosen model and methods for comparing fitted lines and curves.

PMID- 15250509
TI  - New antibiotics and bacterial resistance. Rational prescribing in pediatric
      infection.

PMID- 15250510
TI  - New antivirals and antiviral resistance.

PMID- 15250511
TI  - Mucosal immunity to infections and its importance in future vaccinology.

PMID- 15250512
TI  - Dynamics of bacterial carriage and disease: lessons from the meningococcus.

PMID- 15250513
TI  - Current management of bacterial meningitis.

PMID- 15250514
TI  - Congenital syphilis resurgent.
AB  - Syphilis is resurgent in many parts of the world. Even in those countries where
      rates have fallen focal outbreaks still occur. Congenital syphilis is an
      inevitable consequence of undetected and untreated syphilis in a pregnant woman.
      Universal screening in pregnancy, even if the positive yield from the test is
      low, remains the keystone to congenital syphilis prevention. Programmatic
      attention to testing, treating, education, and contact tracing in pregnancy and
      subsequent late trimester retesting of high-risk women will lower congenital
      infection rates. Any slip in this meticulous process inevitably leads to
      resurgence of congenital syphilis.

PMID- 15250515
TI  - Antibiotics for acute otitis media in the era of antibiotic resistance--what are
      the choices?

PMID- 15250516
TI  - Bone and joint infections in children.

PMID- 15250517
TI  - Sepsis syndrome in children: can we do better?

PMID- 15250518
TI  - Prevention of enteric diseases.
AB  - Enteric diseases remain a high public health priority for much of the world's
      population. Improvement of sanitation and hygiene would have a favorable impact
      on this problem, but resources are not available to effect these interventions
      worldwide. Thus, vaccines against some diarrheal diseases are needed urgently.
      There has been much success in this arena, but much more needs to be done.
      Solutions will depend on new and old technologies and on continued dedication of
      human and financial resources to address problems of global significance.

PMID- 15250519
TI  - Viral hepatitis in children.

PMID- 15250521
TI  - Bacterial and fungal infections in the neonate: current diagnosis and therapy.

PMID- 15250520
TI  - Controversies in neonatal infection.
AB  - Antibiotics are an important part of neonatal care, but we must be careful that a
      short-sighted approach to their use does not magnify the problems they are
      designed to prevent. Prevention of infections by good infection control practices
      and minimizing risk factors for sepsis is just as important as appropriate
      antibiotic use. Attempts to eradicate colonizing organisms of low virulence may
      result in their replacement by more problematic organisms, so over-vigorous use
      of antibiotics to try to prevent infections is not always wise.

PMID- 15250522
TI  - Pertussis is back and now what?

PMID- 15250523
TI  - The immunocompromised host: the patient with recurrent infection.

PMID- 15250524
TI  - Febrile neutropenia: past, present and future.

PMID- 15250525
TI  - Malaria.

PMID- 15250526
TI  - HIV-1 infection in children: current practice and future predictions.

PMID- 15250527
TI  - Preventing perinatal transmission of HIV--are we doing enough?

PMID- 15250528
TI  - Congenital cytomegalovirus infection: epidemiology and treatment.
AB  - Congenital CMV infection remains a major problem worldwide. Current therapeutic
      efforts with ganciclovir have been limited to babies with extensive disease. The
      potential utility for children with less severe disease remains to be determined.
      Hopefully, the availability of newer compounds with an improved safety profile
      that will soon enter clinical trials (GW1263) provides hope that treatment for
      children with congenital CMV can lead to enhanced efficacy. Similar to our
      understanding of the treatment of congenital Toxoplasma gondii infections, long
      term therapy, even up to a year or longer may be required. Ideally, the best
      approach would be the development of an efficacious vaccine. Regardless, current
      clinical efforts define a new era for the treatment of congenital infections.

PMID- 15250529
TI  - Global control of rotavirus disease.

PMID- 15250530
TI  - RSV and influenza. Treatment and prevention.

PMID- 15250531
TI  - Encephalitis--beyond aciclovir.

PMID- 15250532
TI  - Current issues in managing group A streptococcal infections.

PMID- 15250533
TI  - Kawasaki disease and toxic shock syndrome--at last the etiology is clear?
AB  - A decade after the superantigen hypothesis for KD was first suggested, it has
      still not been either proven or refuted conclusively. Although initial optimism
      for the hypothesis was quashed by a series of published papers apparently
      refuting the idea, in the last few years there have been a number of good studies
      providing evidence in support of the superantigen hypothesis. Whether this
      renewed enthusiasm is justified will hopefully become clear in the near future.
      Ultimately, accurate diagnosis, more targeted treatment, and preventative
      strategies depend on the unraveling of the immunopathogenesis of this disease.

PMID- 15250534
TI  - The last of the meningococcus?

PMID- 15250535
TI  - The potential of pneumococcal conjugate vaccines to reduce antibiotic resistance.

PMID- 15250536
TI  - Is Haemophilus influenzae type b disease finished?

PMID- 15250537
TI  - Strategies for preventing group B streptococcal disease.

PMID- 15250538
TI  - Recent advances in the therapy against invasive aspergillosis.

PMID- 15250539
TI  - Glutathione depletion modulates methanol, formaldehyde and formate toxicity in
      cultured rat conceptuses.
AB  - The proposed use of methanol (H3COH) as an alternative to fossil fuels has
      prompted concern about potential health risks resulting from widespread
      environmental exposure. Methanol is teratogenic in rodents and, although the
      exact toxic species is not known, teratogenesis may result from the enzymatic
      biotransformation of H3COH to formaldehyde (CH2O) and formic acid causing
      increased biological reactivity and toxicity. A protective role for the
      antioxidant glutathione (GSH) has been described for H3COH, CH2O and formic acid
      toxicity in various biological systems but has yet to be evaluated in the
      developing conceptus. Whole embryo culture studies were conducted using GD 10-11
      rat conceptuses to elucidate the relationship between H3COH and its metabolites
      and GSH status. Methanol exposure produced a decrease in normal growth parameters
      and a dose-dependent loss of viability. CH2O had deleterious effects on embryo
      growth and viability. Sodium formate (HCOONa) exposure resulted in a high
      mortality rate but viable embryos did not manifest any abnormalities. Methanol,
      CH2O, and HCOONa all produced a significant depletion of GSH in both embryo and
      VYS. Inhibition of GSH synthesis by L-buthionine-S,R-sulfoximine (BSO) treatment
      exacerbated H3COH, CH2O and HCOONa embryotoxicity. Interestingly, only H3COH/BSO
      and CH2O/BSO co-treatments caused increased malformation, while embryos treated
      with HCOONa/BSO did not produce any developmental deformities. These results
      implicate CH2O as the most embryotoxic H3COH metabolite, on a molar basis, in
      terms of causing dysmorphogenesis, alterations of normal growth parameters and
      embryolethality. HCOONa was selectively embryolethal and did not produce
      dysmorphogenesis. CH2O toxicity is potentiated by GSH depletion, indicating that
      GSH may be more directly involved in its detoxication in the embryo.

PMID- 15250540
TI  - Cell and toxicant specific phosphorylation of conexin43: effects of lindane and
      TPA on rat myometrial and WB-F344 liver cell gap junctions.
AB  - Previous studies showed that the pesticide lindane (gamma-hexachlorocyclohexane)
      inhibits gap junction intercellular communication in rat myometrial cells. The
      present study tested the hypothesis that lindane and the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) inhibit gap junction communication in rat
      myometrial and liver WBr-F344 cells by the common mechanism of increasing
      phosphorylation of the gap junction protein connexin43. We evaluated changes of
      connexin43 phosphorylation using Western blot of standard SDS-PAGE gels and cell
      immunostaining, and we monitored gap junction communication using microinjection
      and transfer of Lucifer yellow dye. Exposure of rat myometrial cells to lindane
      or TPA nearly abolished dye transfer but did not alter the electrophoretic
      mobility of connexin43, and neither lindane nor TPA increased phosphorylation of
      connexin43 as assessed by immunoblot with anti-phospho-connexin43 (S368)
      antibody. However, TPA increased punctate immunofluorescence staining of phospho
      connexin43 (S368) in myometrial cells whereas lindane had no such effect. In WBr
      F344 cells, lindane and TPA inhibited dye transfer. Lindane increased
      immunostaining for phospho-connexin43 (S368) in WBr-F344 cells without altering
      the abundance, electrophoretic mobility or phosphorylation of connexin43 as
      detected in immunoblots. TPA intensified a slower migrating connexin43 band and
      increased phospho-connexin43 (S368) in immunoblots, and intensified phospho
      connexin43 immunostaining at WBr-F344 cell interfaces and nuclear regions. These
      results show that phosphorylation of connexin43 at serine 368 occurred in cell
      and toxicant specific manners and was independent of changes in electrophoretic
      mobility in standard SDS-PAGE gels. Moreover, lindane inhibited gap junction
      communication in myometrial cells by a mechanism that was not be explained by
      changes in phosphorylation of connexin43.

PMID- 15250541
TI  - Mercury inhibits rat liver and kidney glucocorticoid receptor hormone binding
      activity.
AB  - The present study was focused on the influence of mercury on the rat liver and
      kidney glucocorticoid receptor (GR) binding properties. The time-course and dose
      dependence of mercury effects, as well as possible involvement of thiol groups
      were examined after in vivo and in vitro administration of the metal in the form
      of HgCl2. Mercury led to reduction of the liver and kidney GR hormone binding
      capacity. In both examined tissues maximal reduction was noticed 4 h after
      administration of the metal at 2 and 3 mg Hg/kg bw, but the effect was more
      prominent in kidney as compared to liver. On the other hand, binding affinity in
      the two tissues was similar. The complete reversal of mercury effects on GR
      binding capacity by 10 mmol/L DTT was achieved in liver and partially in kidney.
      The reversal by DTT suggested that mercury caused the decrease of GR binding
      activity by interacting with thiol groups. The difference in the response of the
      two tissues reflected the fact that kidney contained a higher mercury
      concentration and a lower thiol content in comparison to liver. The implicated
      thiols probably belong to GR, since when applied in vitro at 0 degrees C, mercury
      produced reduction of the receptor binding activity similar to that observed in
      vivo. GR protein level examined by quantitative Western blot was either
      unchanged, when determined by polyclonal antibody, or reduced, when determined by
      BuGR2 antibody, suggesting that Hg might affect BuGR epitope availability.

PMID- 15250542
TI  - Cytotoxic effects of environmentally relevant chlorophenols on L929 cells and
      their mechanisms.
AB  - The chlorophenol chemicals (CPs) are a major class of widely distributed and
      frequently occurring persistent environmental pollutants. Pentachlorophenol (PCP)
      has been proposed to be procarcinogen in rodents and in possibly human beings.
      Human beings also easily expose to other chlorophenol chemicals, including 4
      chlorophenol (CP), 2,4-dichlorophenol (DCP), 2,3,4-trichlorophenol (TCP),
      prompting this investigation of their comparative cytotoxic effects and cell
      death mechanisms, assayed in fibroblast L929 cells. The effective concentration
      for half-maximal response (EC50 values at 24 h for CP, DCP, TCP, and PCP are
      2.18, 0.83, 0.46, and 0.11 mmol/L respectively and the EC50 values at 48 h are
      1.18, 0.13, 0.08, and 0.06 mmol/L respectively by using 3-(4,5-dimethylthiazd-2
      yl)-2,5-diphenyltentrazolium bromide (MTT) reduction assay. A clear structure
      activity relationship was observed between toxicity of CPs and their octanol
      water partition coefficients. The further studies indicate that CP, DCP, and TCP
      induce apoptosis in L929 cells in a concentration or time-dependent manner, but
      PCP mediates cell death more characteristic of necrosis than apoptosis. These
      results not only demonstrate that L929 cell growth inhibition bioassay may be
      useful to provide the comparative evaluation of toxicity of CPs in vitro, but
      also implicate that CP, DCP, TCP, in comparison with PCP, can induce L929 cell
      death by apoptosis, resulting in lower procarcinogensis, which may help to
      elucidate the molecular basis for the adverse health effects associated with CPs
      exposure.

PMID- 15250543
TI  - Cryogenic far-infrared laser absorptivity measurements of the Herschel Space
      Observatory telescope mirror coatings.
AB  - Far-infrared laser calorimetry was used to measure the absorptivity, and thus the
      emissivity, of aluminum-coated silicon carbide mirror samples produced during the
      coating qualification run of the Herschel Space Observatory telescope to be
      launched by the European Space Agency in 2007. The samples were measured at 77 K
      to simulate the operating temperature of the telescope in its planned orbit about
      the second Lagrangian point, L2, of the Earth-Sun system. Together, the
      telescope's equilibrium temperature in space and the emissivity of the mirror
      surfaces will determine the far-infrared-submillimeter background and thus the
      sensitivity of two of the three astronomical instruments aboard the observatory
      if stray-light levels can be kept low relative to the mirror emission.
      Absorptivities of both clean and dust-contaminated samples were measured at 70,
      118, 184, and 496 microm. Theoretical fits to the data predict absorptivities of
      0.2-0.4% for the clean sample and 0.2-0.8% for the dusty sample, over the
      spectral range of the Herschel Space Observatory instruments.

PMID- 15250544
TI  - Profiled bar transmission gratings: soft-x-ray calibration of new Kirchoff
      solutions.
AB  - A new analytical model, derived rigorously from scalar diffraction theory,
      accurately fits soft-x-ray measurements of symmetrical profile gold transmission
      gratings in all diffracted orders. The calibration system selects numerous photon
      energies by use of a high-resolution grazing-incidence monochromator and a dc e
      beam source. Fine-period free-standing gratings exhibit limited performance and
      require such testing to determine parameters of and select acceptable gratings
      for use in time-resolved (0.25 ns) spectrographs of known radiometric response.
      Unfolded spectra yield a Z-pinch plasma peak kT approximately 250 eV, total
      radiated energy approximately 900 kJ, and a pinch-driven gold-wall hohlraum
      Planckian kT approximately 86 eV.

PMID- 15250545
TI  - Extreme-ultraviolet efficiency measurements of freestanding transmission
      gratings.
AB  - We report new, near-normal-incidence, transmission grating efficiency results at
      selected extreme-ultraviolet wavelengths between 4.5 and 30.5 nm for two
      transmission gratings, one with a period of 200 nm and the other with a period of
      400 nm. These gratings consist of opaque gold bars separated by open spaces that
      have been produced by photolithography techniques commonly used to produce
      electronic components. The gold bars and the open spaces are nominally of the
      same width. Both gratings have a thickness of 470 nm. The transmission efficiency
      at the central, first, and, when possible, second order of diffraction was
      measured. In addition, guided-wave phenomena at nonnormal angles of incidence, as
      well as transmission differences depending on which side of the grating was
      illuminated, were investigated. The observed guided-wave effects allow one to
      selectively enhance the transmission of the grating at desired wavelengths, as is
      realized with a blazed reflection grating.

PMID- 15250546
TI  - Fourier-domain holography in photorefractive quantum-well films.
AB  - Fourier-domain holography (FDH) is investigated as a candidate for holographic
      optical coherence imaging to produce real-time images of structure inside living
      tissue and turbid media. The effects of spatial filtering, the background
      intensity distributions, and the role of background noise in determining dynamic
      range are evaluated for both FDH and image-domain holography (IDH). The grating
      washout effect in FDH (edge enhancement) is removed by use of a vibrating
      diffuser that consequently improves the image quality. By comparing holographic
      images and background images of FDH and IDH we show that FDH provides a higher
      dynamic range and a higher image quality than IDH for this specific application
      of imaging diffuse volumetric objects.

PMID- 15250547
TI  - Heterodyne interferometric system with subnanometer accuracy for measurement of
      straightness.
AB  - A generalized laser interferometer system based on three design principles, i.e.,
      heterodyne frequency, prevention of mixing, and perfect symmetry, is described.
      These design principles give rise to an interferometer in a highly stable system
      with no periodic nonlinearity. A novel straightness sensor, consisting of a
      straightness prism and a straightness reflector, is incorporated into the
      generalized system to form a straightness interferometer. A Hewlett-Packard
      commercial linear interferometer was used to validate the interferometer's
      parameters. Based on the present design, the interferometer has a gain of 0.348,
      a periodic nonlinearity of less than 40 pm, and a displacement noise of 12
      pm/mean square root of Hz at a bandwidth of 7.8 kHz. This system is useful for
      precision straightness measurements.

PMID- 15250548
TI  - Evaluation of seeing-induced cross talk in tip-tilt-corrected solar polarimetry.
AB  - We reanalyze the effects of atmosphere-induced image motions on the measurement
      of solar polarized light using a formalism developed by Lites. Our reanalysis is
      prompted by the advent of adaptive optics (AO) systems that reduce image motion
      and higher-order aberrations, by the availability of liquid crystals as
      modulation devices, and by the need to understand how best to design polarimeters
      for future telescopes such as the Advanced Technology Solar Telescope. In this
      first attempt to understand the major issues, we analyze the influence of
      residual image motion (tip-tilt) corrections of operational AO systems on the
      cross talk between Stokes parameters and present results for several polarization
      analysis schemes. Higher-order wave-front corrections are left for future
      research. We also restrict our discussion to the solar photosphere, which limits
      several important parameters of interest, using some recent magnetoconvection
      simulations.

PMID- 15250549
TI  - Fabrication and characterization of fluorescent rare-earth-doped glass-particle
      based tips for near-field optical imaging applications.
AB  - Fluorescent rare-earth-doped glass particles glued to the end of an atomic force
      microscope tip have been used to perform scanning near-field optical measurements
      on nanostructured samples. The fixation procedure of the fluorescent fragment at
      the end of the tip is described in detail. The procedure consists of depositing a
      thin adhesive layer on the tip. Then a tip approach is performed on a fragment
      that remains stuck near the tip extremity. To displace the particle and position
      it at the very end of the tip, a nanomanipulation is achieved by use of a second
      tip mounted on piezoelectric scanners. Afterward, the particle size is reduced by
      focused ion beam milling. These particles exhibit a strong green luminescence
      where excited in the near infrared by an upconversion mechanism. Images obtained
      near a metallic edge show a lateral resolution in the 180-200-nm range. Images we
      obtained by measuring the light scattered by 250-nm holes show a resolution well
      below 100 nm. This phenomenon can be explained by a local excitation of the
      particle and by the nonlinear nature of the excitation.

PMID- 15250550
TI  - Frequency response characteristics of a birefringent lens with off-axis
      aberrations.
AB  - We report the frequency response characteristics of an optical system consisting
      of a lens made of a uniaxial birefringent crystal sandwiched between two linear
      polarizers; the lens has prespecified off-axis aberrations such as primary
      astigmatism and primary coma. An analytical expression is obtained for the
      optical transfer function of the proposed system by use of the autocorrelation of
      the pupil function over the lens aperture. Some specific cases are computed and
      illustrated graphically. It has been shown that the proposed system has imaging
      characteristics distinctly different from those of an ordinary glass lens, and
      these may be advantageous for better balancing of aberrations in conventional
      imaging systems.

PMID- 15250551
TI  - Time-frequency signal processing of terahertz pulses.
AB  - We demonstrate that some signal-processing techniques, such as the fractional
      Fourier transform and the spectrogram, which are known to be effective for
      optical signals, can be implemented at terahertz frequencies and with available
      terahertz devices. These techniques, contrary to the frequency-resolved optical
      gating method for pulse characterization, do not require nonlinear media, which
      do not exist at terahertz frequencies. Thus the fractional Fourier transform or
      the spectrogram offers the only possibility of characterizing terahertz pulses
      simultaneously in time and frequency.

PMID- 15250552
TI  - Diffraction of optical communication Gaussian beams by volume gratings:
      comparison of simulations and experimental results.
AB  - The diffraction effects induced by a thick holographic grating on the propagation
      of a finite Gaussian beam are theoretically analyzed by means of the coupled-wave
      theory and the beam propagation method. Distortion of the transmitted and
      diffracted beams is simulated as a function of the grating parameters.
      Theoretical results are verified by experimentation realized by use of LiNbO3
      volume gratings read out by a 1550-nm Gaussian beam, typical of optical fiber
      communications. This analysis can be implemented as a useful tool to aid with the
      design of volume grating-based devices employed in optical communications.

PMID- 15250553
TI  - Scintillation and beam-wander analysis in an optical ground station-satellite
      uplink.
AB  - In an optical communication link between an optical ground station and a
      geostationary satellite the main problems appear in the uplink and are due to
      beam wander and to scintillation. Reliable methods for modeling both effects
      simultaneously are needed to provide an accurate tool with which the robustness
      of the communication channel can be tested. Numerical tools, especially the split
      step method (also referred to as the fast-Fourier-transform beam propagation
      method), have demonstrated their ability to deal with problems of optical
      propagation during atmospheric turbulence. However, obtaining statistically
      significant results with this technique is computationally intensive. We present
      an analytical-numerical hybrid technique that provides good information on the
      variance in optical irradiance with an important saving of time and computational
      resources.

PMID- 15250554
TI  - Amplitude-modulated laser imager.
AB  - Laser systems have been developed to image underwater objects. However, the
      performance of these systems can be severely degraded in turbid water. We have
      developed a technique using modulated light to improve underwater detection and
      imaging. A program, Modulated Vision System (MVS), which is based on a new
      theoretical approach, has been developed to predict modulated laser imaging
      performance. Experiments have been conducted in a controlled laboratory
      environment to test the accuracy of the theory as a function of system and
      environmental parameters. Results show a strong correlation between experiment
      and theory and indicate that the MVS program can be used to predict future system
      performance.

PMID- 15250555
TI  - Tapered fiber bundles for combining high-power diode lasers.
AB  - Tapered fiber bundles are often used to combine the output power of several
      semiconductor lasers into a multimode optical fiber for the purpose of pumping
      fiber lasers and amplifiers. It is generally recognized that the brightness of
      such combiners does not exceed the brightness of the individual input fibers. We
      report that the brightness of the tapered fibers (and fiber bundles) depends on
      both the taper ratio and the mode-filling properties of the beams launched into
      the individual fibers. Brightness, therefore, can be increased by selection of
      sources that fill a small fraction of the input fiber's modal capacity. As proof
      of concept, we present the results of measurements on tapered fiber-bundle
      combiners having a low-output etendue. Under low mode-filling conditions per
      input multimode fiber (i.e., fraction of filled modes < or =0.29), we report
      brightness enhancements of 8.0 dB for 19 x 1 bundles, 6.7 dB for 7 x 1 bundles,
      and 4.0 dB for 3 x 1 combiners. Our measured coupling efficiency variations of
      approximately 1%-2% among the various fibers in a given bundle confirm the
      uniformity and quality of the fabricated devices.

PMID- 15250556
TI  - Ultraviolet-visible imaging acousto-optic tunable filters in KDP.
AB  - There is a need to develop large-aperture acousto-optic tunable filters (AOTFs)
      in the UV region for applications in astronomy, environmental sciences, biology,
      etc. We have developed a high-quality noncollinear AOTF cell that uses a single
      crystal of KDP that has nearly a four times larger acousto-optic figure of merit,
      M2, than quartz. The linear and angular apertures of this cell are 1.5 cm x 1.5
      cm and 1.2 degrees, respectively. The spectral range is 220-480 nm, with 160-cm(
      1) spectral resolution and high transmission in the UV. We present an analysis of
      the design and describe the characterization results.

PMID- 15250557
TI  - Increasing the output of a Littman-type laser by use of an intracavity Faraday
      rotator.
AB  - We present a method of external-cavity diode-laser grating stabilization that
      combines the high output power of the Littrow design with the fixed output
      pointing of the Littman-Metcalf design. Our new approach utilizes a Faraday
      effect optical isolator inside the external cavity. Experimental testing and a
      model that describes the tuning range and optimal tuning parameters of the laser
      are described. Preliminary testing of this design has resulted in a short-term
      linewidth of 360 KHz and a side-mode suppression of 37 dB. The laser tunes mode
      hop free over 7 GHz, and we predict that much larger tuning ranges are possible.

PMID- 15250558
TI  - Raman-shifted eye-safe aerosol lidar.
AB  - The design features of, and first observations from, a new elastic backscatter
      lidar system at a wavelength of 1543 nm are presented. The transmitter utilizes
      stimulated Raman scattering in high-pressure methane to convert fundamental
      Nd:YAG radiation by means of the 1st Stokes shift. The wavelength-converting gas
      cell features multipass operation and internal fans. Unlike previous lidar
      developments that used Raman scattering in methane, the pump beam is not focused
      in the present configuration. This feature prevents optical breakdown of the gas
      inside the cell. Additionally, the gas cell is injection seeded by a diode to
      improve conversion efficiency and beam quality. The receiver uses a 40.6-cm
      diameter telescope and a 200-microm InGaAs avalanche photodiode. The system is
      capable of operating in a dual-wavelength mode (1064 and 1543 nm simultaneously)
      for comparison or in a completely eye-safe mode. The system is capable of
      transmitting an energy of more than 200 mJ/pulse at 10 Hz. Aerosol backscatter
      data from vertical and horizontal pointing periods are shown.

PMID- 15250559
TI  - Retrieving seawater-backscattering profiles from coupling Raman and elastic lidar
      data.
AB  - We propose a technique for retrieving seawater-backscattering profiles that is
      based on the joint use of elastic and Raman lidar returns. We suggest using two
      lidar channels: the Raman channel and the elastic channel with a light frequency
      equal to a half-sum of initial and Raman-shifted frequencies of the Raman
      channel. These specific wavelengths provide the same attenuation laws for elastic
      and Raman signals if absorption and scattering spectra can be approximated by a
      power law. In particular, seawater supplies such a possibility in the region of
      400-500 nm if extremely bioproductive waters are not considered and the
      chlorophyll absorption peak at 440 nm does not come out of the background of
      dissolved organic matter absorption. With these specific initial wavelengths, the
      elastic and Raman lidar returns differ only in the backscattering coefficients.
      Because the Raman-backscattering coefficient is constant along the profile, the
      (elastic-to-Raman) ratio of these lidar returns directly produces the profile of
      the elastic-backscattering coefficient. This technique stays valid even under
      multiple-scattering conditions, which is of great importance for seawater
      sounding.

PMID- 15250560
TI  - Spatial and temporal evolution of argon sparks.
AB  - Optical emission spectroscopic studies of laser-created argon sparks are carried
      out. Pulses of 532 nm and 8 ns from a frequency-doubled Nd:YAG laser are used to
      create an argon spark at 1 atm. Gated photography of 2 ns is used to investigate
      spark evolution at early times. Electron temperature and density measurements are
      made from the spectral data. The Stark broadening of emission lines is used to
      determine the electron density, and the Boltzmann plot of the singly ionized
      argon-line intensities is exploited for determination of the electron
      temperature. The dependence on electron temperature and density on different
      experimental parameters, such as distance from the focal point, delay time after
      the initiation of the spark, and laser energy, are discussed.

PMID- 15250561
TI  - Picosecond-resolution soft-x-ray laser plasma interferometry.
AB  - We describe a soft-x-ray laser interferometry technique that allows two
      dimensional diagnosis of plasma electron density with picosecond time resolution.
      It consists of the combination of a robust high-throughput amplitude-division
      interferometer and a 14.7-nm transient-inversion soft-x-ray laser that produces
      approximately 5-ps pulses. Because of its picosecond resolution and short
      wavelength scalability, this technique has the potential for extending the high
      inherent precision of soft-x-ray laser interferometry to the study of very dense
      plasmas of significant fundamental and practical interest, such as those
      investigated for inertial confinement fusion. Results of its use in the
      diagnostics of dense large-scale laser-created plasmas are presented.

PMID- 15250562
TI  - Portal hypertensive intestinal vasculopathy: the jejunal story.

PMID- 15250563
TI  - Serum carnitine and selenium levels in children with celiac disease.
AB  - BACKGROUND AND AIM: Celiac disease (CD) is a gluten-induced enteropathy that
      results in malabsorption of nutrients. We studied the serum levels of carnitine
      and selenium in children with CD. METHODS: Serum levels of free carnitine and
      selenium were studied in 30 children (mean age 8.1 [4.4] years) with CD and 30
      age- and gender-matched healthy children. All patients had type 3 duodenal
      lesions. The mean (SD) serum levels of free carnitine and selenium were lower
      among patients with CD (24.5 [7.7] micromol/mL and 52.1 (12.9) micromol/mL,
      respectively) than among healthy controls (29.4 [9.2] and 65.1 [17.2]
      micromol/mL; p < 0.05 each). Levels were similar in children with and without
      diarrhea. CONCLUSIONS: Serum carnitine and selenium levels are decreased in
      children with CD, probably due to malabsorption.

PMID- 15250564
TI  - Extraintestinal manifestations of idiopathic ulcerative colitis in northwestern
      India.
AB  - OBJECTIVE: To determine the frequency of extraintestinal manifestations in
      patients with idiopathic ulcerative colitis. METHODS: 46 patients underwent
      detailed clinical, biochemical and radiological evaluation. RESULTS: One patient
      (2%) had peripheral arthritis and two patients (4%) had ocular involvement in the
      form of anterior uveitis. No patient had mucocutaneous, vascular, or
      hepatobiliary manifestations, or sacroiliitis. CONCLUSIONS: The frequency of
      extraintestinal manifestations in patients with IUC in northwestern India is low.

PMID- 15250565
TI  - Randomized, double-blind trial comparing topical nitroglycerine with xylocaine
      and Proctosedyl in idiopathic chronic anal fissure.
AB  - OBJECTIVE: To compare symptomatic relief, healing, and changes in maximal anal
      resting pressure with the use of topical formulations in patients with chronic
      anal fissure. METHODS: Sixty-four consecutive patients with chronic anal fissure
      were randomized into 4 groups that received, in a double-blind manner, a topical
      ointment that contained 0.2% nitroglycerine (GTN), 5% xylocaine, Proctosedyl
      (hydrocortisone acetate, heparin, framycetin sulfate, esculoside, ethoform,
      butoform) or petroleum jelly (Vaseline), to be applied twice daily. Patients were
      reviewed at 2-week intervals for 6 weeks. Anal manometry was done before, and 20
      minutes after, the first application of the ointment. RESULTS: There was
      significant (p < 0.0001) reduction in mean anal resting pressure after
      application of GTN, but not any other ointment. Of 16 patients receiving GTN,
      complete pain relief occurred in 6 and 15 patients after 2 and 4 weeks of
      treatment, respectively; this was more frequent than in the other 3 groups. At 6
      weeks also, complete pain relief occurred more often with GTN than with Vaseline
      or xylocaine. After 4 weeks of treatment, 3 patients on GTN had complete healing
      of fissure as compared to one each in the xylocaine and Proctosedyl groups and
      none in the Vaseline group. At 6 weeks, healing of fissure had occurred in 15 of
      16 patients receiving GTN as compared to 4 receiving Vaseline, 11 receiving
      xylocaine, and 12 on Proctosedyl. CONCLUSIONS: Topical nitroglycerine produces
      'chemical sphincterotomy' with reduction in mean anal resting pressure. Pain
      relief and healing of fissure occurred earlier with GTN than with other
      treatments. GTN should be considered as the treatment of choice for the non
      surgical management of patients with chronic anal fissure.

PMID- 15250566
TI  - Etiological spectrum of sporadic malabsorption syndrome in northern Indian adults
      at a tertiary hospital.
AB  - BACKGROUND: The etiology of malabsorption syndrome (MAS) may differ in different
      geographical regions. Limited data are available on the etiological spectrum of
      MAS among Indian adults. METHODS: Ninety-nine consecutive adult patients with MAS
      (urine d-xylose <1 g/5 g/5 h with or without increased fecal fat (> or =7 g/24 h)
      were evaluated for cause of MAS using standard criteria. Past medical records
      were examined to know the nature of treatment received. RESULTS: The etiology of
      MAS was: tropical sprue 39, celiac disease 9, Crohn's disease 9, giardiasis 8,
      small intestinal bacterial overgrowth in absence of another cause of MAS 8,
      panhypogammaglobulinemia 2 (one with strongyloidiasis), intestinal
      lymphangiectasia 1, intestinal tuberculosis 4, idiopathic 15, acquired
      immunodeficiency syndrome 2, and amyloidosis 2. Twenty-eight patients had
      received anti-tubercular treatment earlier. CONCLUSIONS: Tropical sprue, celiac
      disease and Crohn's disease are common causes of MAS in Indian adults.
      Inappropriate anti-tubercular treatment is common in them and needs to be
      discouraged.

PMID- 15250567
TI  - Portal hypertensive jejunopathy: a case control study.
AB  - BACKGROUND: Small bowel mucosa is a recognized potential source of bleeding in
      portal hypertension. However, the frequency of its involvement is not known.
      AIMS: To document the nature, severity and frequency of endoscopic and histologic
      changes in the jejunum in patients with portal hypertension. METHODS: Forty
      consecutive patients with portal hypertension and 43 patients with non-ulcer
      dyspepsia (controls) underwent push enteroscopy and jejunal, duodenal and gastric
      biopsies. Biopsies were randomized and examined by a blinded pathologist for
      inflammation and vascular dilatation, which was quantified by morphometry.
      RESULTS: Endoscopic jejunopathy was observed in 6 patients and none of the
      control subjects. All patients with jejunopathy had portal hypertensive
      gastropathy (PHG) and 5 had duodenopathy. Vascular dilatation was observed in 15
      patients and 25 control subjects (p = ns). The degree of vascular dilatation was
      similar in both groups. Inflammatory changes were observed in 24 patients and 25
      control subjects (p = 0.05). CONCLUSIONS: Endoscopic jejunopathy was present in
      15% of patients with portal hypertension. These changes were mild in 83% of them.
      All patients with jejunopathy also had PHG. Histologic changes were similar in
      patients and control subjects.

PMID- 15250568
TI  - The management of bile duct stones.
AB  - Bile duct stones are almost always associated with gallbladder stones and coexist
      with gallbladder stones in approximately 10% of patients. The frequency of
      coexisting bile duct stones increases with advancing age. In patients with stones
      in both the gallbladder and bile duct, therapeutic options for the latter include
      laparoscopic or open exploration of the bile duct, and pre-operative and post
      operative endoscopic sphincterotomy and stone extraction. Endoscopic
      sphincterotomy remains the treatment of choice for bile duct stones after
      cholecystectomy. However, management algorithms in individual institutions will
      be influenced by surgical and endoscopic expertise and by other factors such as
      overall costs. After surgical or endoscopic removal of bile duct stones,
      estimates of the lifetime risk of recurrent stones range from 5%-20%. Increased
      life expectancy and the apparent absence of simple preventative measures indicate
      that the burden of bile duct stones on health expenditure is likely to increase
      in many countries.

PMID- 15250569
TI  - Gastrointestinal perforations in neonates with anorectal malformations.
AB  - We describe the presentation and management of gastrointestinal perforation in
      four neonates with anorectal malformations. Two neonates with high malformation
      had pneumoperitoneum on X-ray; surgery revealed sigmoid perforation in one
      patient and transverse colon perforation in the other. Colostomy was done,
      followed by posterior sagittal anorectoplasty at four months; both recovered
      satisfactorily. The third neonate had no radiological feature of gut perforation
      but cecal perforation was found at surgery; the neonate recovered following right
      hemicolectomy with stoma followed by anorectoplasty at five months. The fourth
      neonate presented with clinical and radiological features of perforation and
      recovered satisfactorily after anoplasty and colostomy.

PMID- 15250570
TI  - Achalasia cardia in mother and son.
AB  - Familial occurrence of achalasia cardia is rare. Most associations are among
      siblings or in monozygotic twins. Parent-child association is even rarer and only
      six such instances have been reported till date. We report a 29-year-old man with
      achalasia cardia and his mother who had the same illness two and half years
      later. Both of them were successfully treated with balloon dilatation.

PMID- 15250571
TI  - Bouveret's syndrome--an unusual cause of spontaneous resolution of gastric outlet
      obstruction.
AB  - Gastric outlet obstruction due to a gallstone impacted in the duodenal bulb
      (Bouveret's syndrome) is a rare complication of gallstones. We report a 47-year
      old man with this syndrome in whom the impacted stone migrated uneventfully.

PMID- 15250572
TI  - Perforation of jejunal non Hodgkin's lymphoma.
AB  - Primary gastrointestinal lymphomas are rare. Jejunal non Hodgkin's lymphoma
      presenting as perforative peritonitis is extremely rare. We report a 51-year-old
      man who presented with perforative peritonitis and was detected to have jejunal
      non Hodgkin's lymphoma. He was treated with resection of the affected segment
      with its mesentery and postoperative chemotherapy, and was asymptomatic 5 months
      later.

PMID- 15250573
TI  - Spontaneous perforation--a rare complication of choledochal cyst.
AB  - We report a 2-year-old girl with spontaneous perforation of choledochal cyst.
      Preoperative diagnosis was possible by hepatobiliary scintigraphy. In view of
      emergency presentation and bile peritonitis, management was a staged procedure
      with peritoneal lavage and T-tube drainage of the biliary system, followed by
      excision of the cyst and Roux-en-Y hepatico-jejunostomy 3 months later.

PMID- 15250574
TI  - Adenocarcinoma esophagus with choroid metastasis.
AB  - Metastases to the eye are rare and those from carcinoma esophagus are very rare,
      with only one report in the English literature. We report a 46-year-old man with
      adenocarcinoma of esophagus who developed isolated choroid metastasis after
      definitive treatment of the primary tumor.

PMID- 15250575
TI  - Gastric hemangioma: an unusual cause of upper gastrointestinal bleed.
AB  - We report a 36-year-old lady who presented with hematemesis. Emergency endoscopy
      showed a polypoidal lesion in the gastric fundus that appeared like a varix.
      Celiac angiogram confirmed this to be a hemangioma located in the fundus. This
      was managed by arterial embolization; the patient is symptom-free 6 months later.

PMID- 15250576
TI  - Isolated prostatic metastasis from primary sigmoid colon carcinoma.
AB  - Metastasis to the prostate is extremely uncommon. We report a 38-year-old man
      with sigmoid colon carcinoma, treated with surgery and adjuvant chemotherapy, who
      developed isolated metastasis to the prostate four years after initial treatment.
      He was treated with chemoradiation and remains disease-free three years after
      detection of metastasis.

PMID- 15250577
TI  - Prognostic utility of luminol (5-amino, 2-3 dihydro 1-4 phthalazinedione)
      enhanced neutrophil chemiluminescence in fulminant hepatic failure.

PMID- 15250578
TI  - Hepatitis B control: to vaccinate or not.

PMID- 15250579
TI  - Tea or tobacco: etiology of esophageal cancer in India.

PMID- 15250580
TI  - Symptomatic sinus bradycardia with infliximab.

PMID- 15250582
TI  - Genetic approaches to studying mouse models of human seizure disorders.
AB  - In conclusion, we have discussed a reverse genetics approach to studying seizure
      disorders in mice (Fig. 1), employing a targeted mutagenesis method to exploit
      the genetic defects identified in human epilepsy families. After detailed
      characterization of the nature of the human mutation and the mouse counterpart
      gene, a targeting vector containing the human disease allele is created. The
      endogenous mouse gene is replaced by the human disease allele through homologous
      recombination in ES cells, leading to the generation of chimeric animals. Mice
      carrying one copy or both copies of the human mutation can be bred to study the
      phenotypic effect of heterozygous and homozygous mutations. At this stage, one
      may want to split the newly created mice into two groups. One group will go
      through seizure phenotyping tests, while the other group will be used to generate
      disease allele-carrying mice on a different genetic background. Phenotypic
      characterization of mice on different inbred strains includes behavioral
      monitoring and EEG analysis looking for the occurrence of spontaneous seizures,
      as well as routine cage examination looking for handling-provoked seizure and ECT
      and PTZ- induced seizure paradigms looking for sensitivity to these stimuli. A
      complete evaluation of the seizure phenotype at the whole-animal level
      establishes the relevance of the mouse model to the human condition. Further
      investigation including imaging, electrophysiology and AED response in these
      mouse models will shed light on the mechanistic basis of the convulsive disorder.
      Current epilepsy research in mouse genetics offers promise for understanding the
      molecular mechanisms that underlie epileptogenesis in humans. A large-scale
      forward genetic effort to create novel mouse mutants with seizure phenotypes by
      in vivo chemical mutagenesis with ethyl-nitroso urea (ENU) is underway at the
      Jackson Laboratory (http://www.jax.org/nmf/). Genetic mapping and isolation of
      the affected genes in these seizure-prone models will provide additional
      molecular pathways involved in seizures. The mutant mice generated through both
      forward and reverse genetic approaches will be a valuable resource for the
      biomedical community to study epilepsy at the molecular level and to characterize
      the pathological consequences of seizures in the whole organism.

PMID- 15250581
TI  - Atypical presentation of Boerhaave's syndrome.

PMID- 15250583
TI  - Integrins, synaptic plasticity and epileptogenesis.
AB  - A number of processes are thought to contribute to the development of epilepsy
      including enduring increases in excitatory synaptic transmission, changes in
      GABAergic inhibition, neuronal cell death and the development of aberrant
      innervation patterns in part arising from reactive axonal growth. Recent findings
      indicate that adhesion chemistries and, most particularly, activities of integrin
      class adhesion receptors play roles in each of these processes and thereby are
      likely to contribute significantly to the cell biology underlying
      epileptogenesis. As reviewed in this chapter, studies of long-term potentiation
      have shown that integrins are important for stabilizing activity-induced
      increases in synaptic strength and excitability. Other work has demonstrated that
      seizures, and in some instances subseizure neuronal activity, modulate the
      expression of integrins and their matrix ligands and the activities of proteases
      which regulate them both. These same adhesion proteins and proteases play
      critical roles in axonal growth and synaptogenesis including processes induced by
      seizure in adult brain. Together, these findings indicate that seizures activate
      integrin signaling and induce a turnover in adhesive contacts and that both
      processes contribute to lasting changes in circuit and synaptic function
      underlying epileptogenesis.

PMID- 15250584
TI  - The role of BDNF in epilepsy and other diseases of the mature nervous system.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) is ubiquitous in the
      central nervous system (CNS) throughout life. In addition to trophic effects on
      target neurons, BDNF appears to be part of a general mechanism for activity
      dependent modification of synapses in the developing and adult nervous system.
      Thus, diseases of abnormal trophic support (such as neurodegenerative diseases)
      and diseases of abnormal excitability (such as epilepsy and central pain
      sensitization) can be related in some cases to abnormal BDNF signaling. For
      example, various studies have shown that BDNF is upregulated in areas implicated
      in epileptogenesis, and interference with BDNF signal transduction inhibits the
      development of the epileptic state. Further study of the cellular and molecular
      mechanisms by which BDNF influences cell survival and excitability will likely
      provide novel concepts and targets for the treatment of diverse CNS diseases.

PMID- 15250586
TI  - Plasticity mechanisms underlying mGluR-induced epileptogenesis.
AB  - Transient application of group I metabotropic glutamate receptor (mGluR) agonists
      to hippocampal slices produces ictal-like discharges that persist for hours after
      the removal of the agonist. This effect of group I mGluR stimulation--converting
      a 'normal' hippocampal slice into an 'epileptic-like' one--may represent a form
      of epileptogenesis. Because this epileptogenic process can be induced in vitro
      and it occurs within hours, it has been possible to examine the cellular and
      transduction processes underlying the generation and long-term maintenance of
      ictal-like bursts. ImGluR(V), a voltage-dependent depolarizing current activated
      by group I mGluR agonists, appears to play an important role in the expression of
      the ictal-like bursts. Long-term activation of ImGluR(V) following mGluR
      stimulation is a possible plastic change that enables the long-term maintenance
      of ictal discharges. Induction of ImGluR(V) may represent a cellular event
      underlying the mGluR-induced epileptogenesis.

PMID- 15250587
TI  - Role of the GABA transporter in epilepsy.
AB  - The GABA transporter plays a well-established role in reuptake of GABA after
      synaptic release. The anticonvulsant effect of tiagabine appears to result
      largely from blocking this reuptake. However, there is another side to the GABA
      transporter, contributing to GABA release by reversing in response to
      depolarization. We have recently shown that this form of GABA release is induced
      by even small increases in extracellular [K+], and has a powerful inhibitory
      effect on surrounding neurons. This transporter-mediated GABA release is enhanced
      by the anticonvulsants gabapentin and vigabatrin. The latter drug also potently
      increases ambient [GABA], inducing tonic inhibition of neurons. Here we review
      the evidence in support of a physiological role for GABA transporter reversal,
      and the evidence that it is increased by high-frequency firing. We postulate that
      the GABA transporter is a major determinant of the level of tonic inhibition, and
      an important source of GABA release during seizures. These recent findings
      indicate that the GABA transporter plays a much more dynamic role in control of
      brain excitability than has previously been recognized. Further defining this
      role may lead to a better understanding of the mechanisms of epilepsy and new
      avenues for treatment.

PMID- 15250585
TI  - Vascular endothelial growth factor (VEGF) in seizures: a double-edged sword.
AB  - Vascular endothelial growth factor (VEGF) is a vascular growth factor which
      induces angiogenesis (the development of new blood vessels), vascular
      permeability, and inflammation. In brain, receptors for VEGF have been localized
      to vascular endothelium, neurons, and glia. VEGF is upregulated after hypoxic
      injury to the brain, which can occur during cerebral ischemia or high-altitude
      edema, and has been implicated in the blood-brain barrier breakdown associated
      with these conditions. Given its recently-described role as an inflammatory
      mediator, VEGF could also contribute to the inflammatory responses observed in
      cerebral ischemia. After seizures, blood-brain barrier breakdown and inflammation
      is also observed in brain, albeit on a lower scale than that observed after
      stroke. Recent evidence has suggested a role for inflammation in seizure
      disorders. We have described striking increases in VEGF protein in both neurons
      and glia after pilocarpine-induced status epilepticus in the brain. Increases in
      VEGF could contribute to the blood-brain barrier breakdown and inflammation
      observed after seizures. However, VEGF has also been shown to be neuroprotective
      across several experimental paradigms, and hence could potentially protect
      vulnerable cells from damage associated with seizures. Therefore, the role of
      VEGF after seizures could be either protective or destructive. Although only
      further research will determine the exact nature of VEGF's role after seizures,
      preliminary data indicate that VEGF plays a protective role after seizures.

PMID- 15250588
TI  - GABA and its receptors in epilepsy.
AB  - Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the mammalian brain. It acts through 2 classes of receptors, GABAA receptors that
      are ligand-operated ion channels and the G-protein-coupled metabotropic GABAB
      receptors. Impairment of GABAergic transmission by genetic mutations or
      application of GABA receptor antagonists induces epileptic seizures, whereas
      drugs augmenting GABAergic transmission are used for antiepileptic therapy. In
      animal epilepsy models and in tissue from patients with temporal lobe epilepsy,
      loss in subsets of hippocampal GABA neurons is observed. On the other hand,
      electrophysiological and neurochemical studies indicate a compensatory increase
      in GABAergic transmission at certain synapses. Also, at the level of the GABAA
      receptor, neurodegeneration-induced loss in receptors is accompanied by markedly
      altered expression of receptor subunits in the dentate gyrus and other parts of
      the hippocampal formation, indicating altered physiology and pharmacology of
      GABAA receptors. Such mechanisms may be highly relevant for seizure induction,
      augmentation of endogenous protective mechanisms, and resistance to antiepileptic
      drug therapy. Other studies suggest a role of GABAB receptors in absence
      seizures. Presynaptic GABAB receptors suppress neurotransmitter release.
      Depending on whether this action is exerted in GABAergic or glutamatergic
      neurons, there may be anticonvulsant or proconvulsant actions.

PMID- 15250589
TI  - Role of the depolarizing GABA response in epilepsy.

PMID- 15250590
TI  - Gap junctions, fast oscillations and the initiation of seizures.

PMID- 15250591
TI  - Functional role of proinflammatory and anti-inflammatory cytokines in seizures.
AB  - Recent evidence has shown that proinflammatory and anti-inflammatory molecules
      are synthesized during epileptic activity in glial cells in CNS regions where
      seizures initiate and spread. These molecules are released and interact with
      specific receptors on neurons. Since various cytokines have been shown to affect
      neuronal excitability, this led to the hypothesis that they may have a role in
      altering synaptic transmission in epileptic conditions. Indeed, intracerebral
      application of IL-1beta enhances epileptic activity in experimental models while
      its naturally occurring receptor antagonist (IL-1Ra) mediates anticonvulsant
      actions. Transgenic mice overexpressing IL-1Ra in astrocytes are less susceptible
      to seizures, indicating that endogenous IL-1 has proconvulsant activity. Several
      studies indicate a central role of IL-1beta for the exacerbation of brain damage
      after ischemic, traumatic or excitotoxic insults, suggesting that it may also
      contribute to neuronal cell injury associated with seizures. Finally, a
      functional polymorphism in the IL-1beta gene promoter, possibly associated with
      enhanced ability to produce this cytokine, has been specifically found in
      temporal lobe epilepsy patients with hippocampal sclerosis and in children with
      febrile seizures. Thus, the IL-1 system may represent a novel target for
      controlling seizure activity and/or the associated long-term sequelae.
      Furthermore, these studies suggest that other inflammatory and anti-inflammatory
      molecules produced in the CNS may have a role in the pathophysiology of seizure
      disorders.

PMID- 15250592
TI  - Using the immune system to target epilepsy.

PMID- 15250593
TI  - Cortical dysplasia and epilepsy: animal models.
AB  - Cortical dysplasia syndromes--those conditions of abnormal brain
      structure/organization that arise during aberrant brain development--frequently
      involve epileptic seizures. Neuropathological and neuroradiological analyses have
      provided descriptions and categorizations based on gross anatomical and cellular
      histological features (e.g., lissencephaly, heterotopia, giant cells), as well as
      on the developmental mechanisms likely to be involved in the abnormality (e.g.,
      cell proliferation, migration). Recently, the genes responsible for several
      cortical dysplastic conditions have been identified and the underlying molecular
      processes investigated. However, it is still unclear how the various structural
      abnormalities associated with cortical dysplasia are related to (i.e., "cause")
      chronic seizures. To elucidate these relationships, a number of animal models of
      cortical dysplasia have been developed in rats and mice. Some models are based on
      laboratory manipulations that injure the brain (e.g., freeze, undercut,
      irradiation, teratogen exposure) of immature animals; others are based on
      spontaneous genetic mutations or on gene manipulations (knockouts/transgenics)
      that give rise to abnormal cortical structures. Such models of cortical dysplasia
      provide a means by which investigators can not only study the developmental
      mechanisms that give rise to these brain lesions, but also examine the cause
      effect relationships between structural abnormalities and epileptogenesis.

PMID- 15250594
TI  - Malformations of cortical development: molecular pathogenesis and experimental
      strategies.
AB  - Malformations of cortical development (MCD) are developmental brain lesions
      characterized by abnormal formation of the cerebral cortex and a high clinical
      association with epilepsy in infants, children, and adults. Despite multiple anti
      epileptic drugs (AEDs), treatment of epilepsy associated with MCD may require
      cortical resection performed to remove the cytoarchitecturally abnormal region of
      cortex. Single genes responsible for distinct MCD including lissencephaly,
      subcortical band heterotopia, and tuberous sclerosis, have been identified and
      permit important mechanistic insights into how gene mutations result in abnormal
      cortical cytoarchitecture. The pathogenesis of MCD such as focal cortical
      dysplasia, hemimegalencephaly, and polymicrogyria, remains unknown. A variety of
      new techniques including cDNA array analysis now allow for analysis of gene
      expression within MCD.

PMID- 15250597
TI  - The tetanus toxin model of chronic epilepsy.
AB  - In experimental models of epilepsy, single and recurrent seizures are often used
      in an attempt to determine the effects of the seizures themselves on mammalian
      brain function. These models attempt to emulate as many features as possible of
      their human disease counterparts without many of the confounding factors such as
      underlying disease processes and medication effects. Numerous models have been
      used in the past to address different questions. Nevertheless, the basic
      questions are often the same: 1. Do seizures cause long-term damage? 2. Do
      seizures predispose to chronic epilepsy (epileptogenesis), that is long-term
      spontaneous repetitive seizures? 3. Are these results developmentally regulated?
      4. Are the underlying mechanisms of epileptogenesis and brain damage related? In
      pursuing these questions, the goal is to determine how seizures exert their
      effects and to minimize any side effects from the methods employed to induce the
      seizures themselves. This requires a detailed characterization of the methods
      used to induce seizures. In this chapter, we will review the literature regarding
      the tetanus toxin model of chronic epilepsy with regard to its mechanisms of
      action, clinical comparisons, how it is experimentally implemented and the
      results obtained thus far. These results will be compared to other models of
      chronic epilepsy in order to make generalizations about the effects of repetitive
      seizures in adult and early life. At this time, it appears that repetitive
      seizures cause long-term changes in learning ability and may cause a
      predisposition to chronic seizures at all ages. In younger animals, both features
      of learning impairment and epilepsy are not typically associated with cell loss
      as they are in adult animals. At all ages, some form of synaptic reorganization
      has been demonstrated to occur.

PMID- 15250595
TI  - Functional implications of seizure-induced neurogenesis.
AB  - The neurobiological doctrine governing the concept of neurogenesis has undergone
      a revolution in the past few years. What was once considered dubious is now well
      accepted: new neurons are born in the adult brain. Science fiction is quickly
      becoming a reality as scientists discover ways to convert skin, bone, or blood
      cells into neurons. In the epilepsy arena, widespread interest has developed
      because of the evidence that neurogenesis increases after seizures, trauma, and
      other insults or injuries that alter seizure susceptibility. This review
      discusses some of the initial studies in this field, and their often surprising
      functional implications. The emphasis will be on the granule cells of
      hippocampus, because they are perhaps more relevant to epilepsy than other areas
      in which neurogenesis occurs throughout life, the olfactory bulb and
      subventricular zone. In particular, the following questions will be addressed: 1.
      Do granule cells that are born in the adult brain become functional, and what are
      the limits of their function? Do they behave homogeneously? Results from our own
      laboratory have focused on cells that become established outside the normal
      boundaries of the granule cell layer, forming a group of "ectopic" granule cells
      in the hilar region. 2. Is increased neurogenesis beneficial, or might it
      actually exacerbate seizures? Evidence is presented that supports the hypothesis
      that new granule cells may not necessarily act to ameliorate seizures, and might
      even contribute to them. Furthermore, cognitive deficits following seizures might
      in part be due to new circuits that develop between new cells and the host brain.
      3. How do the new cells interact with the host brain? Several changes occur in
      the dentate gyrus after seizures, and increased neurogenesis is only one of many.
      What is the interdependence of this multitude of changes, if any? 4. Is
      neurogenesis increased after seizures in man? Research suggests that the data
      from human epileptics are actually inconsistent with the studies in animal models
      of epilepsy, because there is little evidence of increased neurogenesis in
      epileptic tissue resected from intractable epileptics. Yet neurogenesis has been
      shown to occur in humans throughout adult life. What might be the reasons for
      these seemingly disparate results?

PMID- 15250596
TI  - Febrile seizures and mechanisms of epileptogenesis: insights from an animal
      model.
AB  - Temporal lobe epilepsy (TLE) is the most prevalent type of human epilepsy, yet
      the causes for its development, and the processes involved, are not known. Most
      individuals with TLE do not have a family history, suggesting that this limbic
      epilepsy is a consequence of acquired rather than genetic causes. Among suspected
      etiologies, febrile seizures have frequently been cited. This is due to the fact
      that retrospective analyses of adults with TLE have demonstrated a high
      prevalence (20-->60%) of a history of prolonged febrile seizures during early
      childhood, suggesting an etiological role for these seizures in the development
      of TLE. Specifically, neuronal damage induced by febrile seizures has been
      suggested as a mechanism for the development of mesial temporal sclerosis, the
      pathological hallmark of TLE. However, the statistical correlation between
      febrile seizures and TLE does not necessarily indicate a causal relationship. For
      example, preexisting (genetic or acquired) 'causes' that result independently in
      febrile seizures and in TLE would also result in tight statistical correlation.
      For obvious reasons, complex febrile seizures cannot be induced in the human, and
      studies of their mechanisms and of their consequences on brain molecules and
      circuits are severely limited. Therefore, an animal model was designed to study
      these seizures. The model reproduces the fundamental key elements of the human
      condition: the age specificity, the physiological temperatures seen in fevers of
      children, the length of the seizures and their lack of immediate morbidity.
      Neuroanatomical, molecular and functional methods have been used in this model to
      determine the consequences of prolonged febrile seizures on the survival and
      integrity of neurons, and on hyperexcitability in the hippocampal-limbic network.
      Experimental prolonged febrile seizures did not lead to death of any of the
      seizure-vulnerable populations in hippocampus, and the rate of neurogenesis was
      also unchanged. Neuronal function was altered sufficiently to promote synaptic
      reorganization of granule cells, and transient and long-term alterations in the
      expression of specific genes were observed. The contribution of these
      consequences of febrile seizures to the epileptogenic process is discussed.

PMID- 15250598
TI  - Brain stimulation as a therapy for epilepsy.
AB  - The failure of current antiepileptic therapies to adequately treat a significant
      number of epileptic patients highlights the need for the development of new
      treatments for the disorder. A new strategy that is currently being developed is
      to deliver electrical stimulation directly to the brain to decrease or prevent
      seizure activity. Clinical evidence that electrical stimulation could interfere
      with seizure activity was initially reported in the 1930's. However, many of
      these early studies consisted of case reports or were poorly controlled. In
      addition, there were a number of studies that failed to observe any beneficial
      effect of brain stimulation on seizures. More recently, deep brain stimulation
      has been used successfully to treat patients with movement disorders and vagus
      nerve stimulation has been shown to effectively decrease seizure activity in a
      select population of epilepsy patients. These advances have led to a
      reexamination of the potential therapeutic benefits of deep brain stimulation for
      the treatment of epilepsy. There is now experimental and clinical evidence that
      direct electrical stimulation of the brain can prevent or decrease seizure
      activity. However, several fundamental questions remain to be resolved. They
      include where in the brain the stimulus should be delivered and what type of
      stimulation would be most effective. One goal of this research is to combine the
      beneficial aspects of electrical stimulation with seizure detection technology in
      an implantable responsive stimulator. The device will detect the onset of a
      seizure and deliver an electrical stimulus that will safely block seizure
      activity without interfering with normal brain function.

PMID- 15250599
TI  - No country mouse: thirty years of effective marketing and health communications.

PMID- 15250600
TI  - ParticipACTION: this mouse roared, but did it get the cheese?

PMID- 15250601
TI  - The mouse under the microscope: keys to ParticipACTION's success.

PMID- 15250602
TI  - Spreading the message through community mobilization, education and leadership: a
      magnanimouse task.

PMID- 15250603
TI  - The challenge of bilingualism: ParticipACTION campaigns succeeded in two
      languages.

PMID- 15250604
TI  - The Mouseketeers: people make the difference.

PMID- 15250605
TI  - The best laid schemes of mice and men... ParticipACTION's legacy and the future
      of physical activity promotion in Canada.

PMID- 15250606
TI  - Ignorance is bliss? An ethical question.

PMID- 15250607
TI  - Leprosy: a disease of the soul.

PMID- 15250608
TI  - Melanoma: a current overview.

PMID- 15250609
TI  - Chemotherapy for pancreatic cancer.

PMID- 15250610
TI  - Diagnosis and management of the patient with tremor.
AB  - Tremor is a common and disabling symptom that is associated with a large number
      of neurological disorders, including ET and PD. The positional properties of the
      tremor allow the clinician to generate a short list of diagnostic possibilities,
      which can then be narrowed down based on the clinical history and the
      neurological examination. A number of medical and surgical therapies are
      available for tremor, but a successful response to treatment depends on an
      accurate diagnosis.

PMID- 15250611
TI  - Access to health care for persons with disabilities in Rhode Island: results from
      the Primary Care Practitioner Survey.

PMID- 15250612
TI  - Breast versus bottle: educating family medicine and OB/GYN residents at Brown
      University.

PMID- 15250613
TI  - Exponential lethality: upper limits on suicide risk assessments.

PMID- 15250614
TI  - Images in Medicine. Gossypiboma.

PMID- 15250615
TI  - Home Health Quality Initiative.

PMID- 15250616
TI  - Hospital patient satisfaction: minority views of the hospital experience.

PMID- 15250617
TI  - Abandonment in the physician-patient relationship.

PMID- 15250618
TI  - Miriam Hospital Morbidity and Mortality Conference, a case of fever.

PMID- 15250619
TI  - May physicians date their patients' relatives? Rethinking sexual misconduct &
      disclosure after Long v. Ostroff.

PMID- 15250620
TI  - The classical origins of Pus.

PMID- 15250621
TI  - Psychiatry of HIV/AIDS.

PMID- 15250622
TI  - Prevalence of HIV/AIDS and psychiatric disorders and their related risk factors
      among adults in Epworth, Zimbabwe.
AB  - OBJECTIVES: To examine the prevalence of HIV infection, neuropsychiatric
      disorders, psychiatric symptoms/signs, alcohol use/misuse, CD4 cell counts and
      risk factors in adult patients. DESIGN: Cross-sectional study. SETTING: Epworth,
      which is about 15 km on the southeastern part of Harare, Zimbabwe. SUBJECTS: Two
      hundred subjects were included in the study out of which six were excluded
      beacause of HIV-1 indeterminate results. MATERIALS AND METHODS: A convenience
      sample of 200 subjects recruited in a cross-sectional study in Epworth, Zimbabwe.
      Six subjects had indeterminate HIV-1 antibody results and were excluded from the
      study. The remaining 194 subjects of whom 101 (52.1%) knew about their sero
      status and were consecutively recruited, whereas, 93 (47.9%) did not know about
      their sero-status and were recruited by a systematic random sampling method (1-in
      3). They were then interviewed about neuropsychiatric disorders using BPRS,
      MADRS, AUDIT and MINI Mental State Test, including the risk factors related to
      HIV infection. After ELISA tests' results, the two groups were combined and then
      categorised into HIV positive (n=115) and HIV negative (n=79) subjects. MAIN
      OUTCOME MEASURES: Prevalence, neuropsychiatric disorders, increased CD4 cell
      counts and risk factors associated with HIV infection. RESULTS: The findings were
      that the overall point prevalence of the HIV infection was 59.3% (115/194).
      Comparative analyses between seropositive and seronegative HIV/AIDS subjects
      showed: over two thirds (71.3%) of the HIV positive subjects suffered from
      psychiatric disorders, more than those with HIV negative 44.3% (OR=3.12, 95%
      CI=1.64-5.95, P=0.0002), and subjects aged 35 years and less were mostly HIV
      seronegatives (n=77.2%, OR=2.34, 95% CI=1.18-4.75, P=0.014). The overall
      prevalence of alcohol use/misuse was 41 (21.1%), with higher prevalence rate
      among HIV positive subjects, 28 (24.3%) than those who were HIV negative, 13
      (16.5%). The commonest psychiatric symptoms/signs (P<0.05) were emotional
      withdrawal, depressed mood, suspiciousness, apparent sadness, reduced sleep and
      suicidal thoughts (especially among women). CONCLUSION: There is very high point
      prevalence of HIV/AIDS and psychiatric disorders, including a moderate prevalence
      rate of alcohol use/misuse in this less affluent community that warranted
      intervention.

PMID- 15250623
TI  - Spectrum and outcome of clinical diseases in adults living with AIDS at the Ogun
      State University Teaching Hospital.
AB  - OBJECTIVES: To evaluate the changing frequency of HIV/AIDS amongst medical
      admissions as well as the spectrum and outcome of clinical diseases among these
      patients. DESIGN: Retrospective study. SETTING: Tertiary hospital in Nigeria.
      PARTICIPANTS: Two hundred and six People Living With AIDS (PLWA) admitted at the
      medical wards during the period 1992 to 2002. INTERVENTION: Treatment was
      symptomatic in all patients and where appropriate, specific treatment was
      administered for indicator diseases. Highly Active Anti-retroviral Therapy
      (HAART) was not used. MAIN OUTCOME MEASURES: Mortality within six months of
      diagnosis. RESULTS: PLWA constituted 4.2% of all medical admissions. The
      frequency increased from 0% in 1992 to 7.6% in 2001, and dropped to 5% by the
      year 2002. Seventy patients (34%) died within six months of diagnosis. RESULTS:
      This study has demonstrated an increasing frequency of HIV/AIDS amongst our
      medical in-patients from none in 1992 to 7.6% in 2001, and thereafter, a decline
      in 2002. We suspect that this decline could be a reflection of the health
      education on HIV, its increasing awareness and the widespread utilisation of
      effective control measures. Furthermore, the administration of highly active anti
      retroviral therapy (HAART) to a segment of PLWA in Sagamu by the community
      medicine department could be contributory. CONCLUSION: A community based study
      would be needed to assess the efficacy or otherwise of these current control
      measures. The advent of saliva and urine tests for HIV detection would ease
      specimen collection and increase compliance and participation at the community
      level.

PMID- 15250624
TI  - Priapism in southwestern Nigeria.
AB  - OBJECTIVES: To determine the aetiology, pattern of presentation, treatment
      regimen and outcome of management of priapism in our environment and to compare
      our findings with previous studies in this country and elsewhere. DESIGN: A 10
      year retrospective study from January 1991 to December 2000. SETTING: Obafemi
      Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. PATIENTS AND
      METHODS: Hospital records of 16 patients managed for priapism over 10 years
      (January 1991 to December 2000) were analysed. Information extracted included the
      age, occupation, duration of symptoms, precipitating factors, past medical
      history, haemoglobin genotype, drug and social history, physical findings,
      treatment regimen, outcome of treatment, complications and duration of follow up.
      Eighteen patients were treated for priapism during the period but only sixteen
      case files available for analysis were reviewed in this study. RESULTS: The mean
      age of the 16 patients under review was 20.4 years (range: 2.5-38 years).
      Thirteen patients (81%) were single and 10 (62.5%) were students. All the
      patients presented late with pain and woody hard penis with mean duration of
      eight days (range; 7 hrs-30 days). Eleven patients (68.7%) had previous episodes
      of priapism. Fourteen patients (87.5%) had sickle cell disease (SCD) and two
      (12.5%) were psychiatric patients on oral chlorpromazine. Associated medical
      conditions include urinary tract infection, malaria, acute urinary retention,
      bone pain crises and acute psychosis. All the patients received initial
      conservative management. Six patients had needle aspiration with irrigation plus
      injection of 2 ml of adrenaline solution (1 ml 1/1000 adrenaline in 200 ml
      saline) in both corpora cavernosa. One (16.7%) out of the six patients achieved
      full detumescence with normal erection. The remaining five patients later had
      cavernotomy with full detumescence and normal erection in three (60%) and weak
      erection in two (40%). Eight patients had Cavernosa-glandular shunt, full
      detumescence and normal erection was achieved in five patients (62.5%) while
      three (37.5%) became impotent. Two of the three patients with impotence presented
      with the longest duration of symptoms (14 and 30 days respectively), while the
      third patient reported earlier after five days, but he had suffered more than six
      (>6) previous attacks of priapism. Duration of hospital stay was 3-10 days and
      the average duration of follow up was 80.7 weeks. CONCLUSION: Sickle cell disease
      account for 87.5% of priapism in our community. Late presentation and previous
      episodes of priapism, which are common features in most of these patients, are
      associated with poor prognosis with higher risk of impotence. Conservative
      management and aspiration with intracavernous adrenaline therapy appears
      ineffective in late case. However, good results obtained with surgery indicate
      that late presentation should not be a deterrent to surgical intervention.
      Surgeries in form of cavernotomy or cavernosa-glandular shunt, when carefully
      done, are effective and safe.

PMID- 15250625
TI  - Histopathologic pattern of thyroid disease.
AB  - BACKGROUND: Diseases of the thyroid are manifested by alteration in hormone
      secretion, enlargement of the thyroid gland (goiter), or both. The principal
      diseases of the thyroid gland are goiter (diffuse or nodular), hypo or
      hyperthyroidism, thyroiditis and neoplasms. The incidence and prevalence of these
      thyroid diseases in a given community are variable depending on various factors.
      Simple (non-toxic) goiter is extremely common throughout the world and is most
      prevalent in mountainous areas. The reported prevalance of goiter in Ethiopia
      varies between 18% and 30%. OBJECTIVE: To review the histopathologic patterns of
      thyroid disease and their relationship with age and sex over a five year period.
      SETTING: Tikur Anbessa teaching and referral hospital, Department of Pathology,
      Faculty of Medicine, Addis Ababa University. METHODS: Retrospective analysis of
      five years biopsy material from patients with thyroid disease. RESULTS: Seven
      hundred and eighty consecutive patients with thyroid disease were included in the
      study. Six hundred and sixty (79%) were found to be non-neoplastic and 164 (21%)
      were neoplastic. Nodular colloid goiter (NCG) were found in 600 (76.9%) cases.
      Adenoma, carcinoma and thyroiditis accounted for 100 (12.8%), 64 (8.2%) and 16
      (2.1%) cases respectively. Female to male ratio was 4.5:1. Eighty five point
      seven per cent of the thyroid diseases were found in the age group 20-59 years.
      CONCLUSION: Nodular colloid goiter is the most prevalent thyroid disease.
      Papillary carcinoma is the most frequent cancer seen in this series. Appropriate
      measures should be taken to reduce the iodine deficiency states in the diet to
      alleviate the social and medical consequences of the NCG. Similary clinical
      evaluation of goiter should be thorough, and use all means especially
      histopathologic study of the specimens to arrive at a definitive diagnosis as
      thyroid carcinoma is not uncommon.

PMID- 15250626
TI  - Blood pressure control in a population where antihypertensives are given free.
AB  - BACKGROUND: Analysis of blood pressure control has shown that optimal blood
      pressure control is generally low in many studies. Poor adherence to therapeutic
      plans and non-compliance are perhaps the most important factors responsible for
      poor control. In most cases poverty has been adduced to be responsible for non
      compliance especially in the sub-Saharan Africa. Assessment of blood pressure
      control in situations where antihypertensives are given free is necessary.
      OBJECTIVES: To assess blood pressure control in a population where
      antihypertensives are given free. SETTING: International institute for tropical
      Agriculture (IITA). DESIGN: Cross-sectional study. SUBJECTS: One hundred and
      forty three consecutive hypertensive subjects (106 males and 37 females) being
      followed-up in the medical clinic of the International Institute for Tropical
      Agriculture (IITA) for variable numbers of years were studied. Blood pressure was
      considered to be well controlled if it was less than 140/90 mmHg and uncontrolled
      if higher than 140/90 mmHg. RESULTS: About 51 (36%) of the subjects may be
      described as being fully controlled on the treatment instituted while 54 (38%) of
      the subjects were not controlled at all. In about 18% of the patients, the
      systolic blood pressure alone was controlled while in 8% the diastolic blood
      pressure alone was controlled. MAIN OUTCOME MEASURES: Level of blood pressure
      control in this study is poor suggesting that availability of free drug alone is
      not enough to improve adherence to antihypertensives. CONCLUSION: The percentage
      of hypertensive patients with optimal blood pressure control in this population
      is low, although this was higher when compared to a report from a similar study
      where drugs were not given free to patients. Physicians managing hypertension in
      such establishments should pay attention to adequate dosing and appropriate
      combination of drugs.

PMID- 15250627
TI  - Iodine concentration in salt at household and retail shop levels in Shebe town,
      south west Ethiopia.
AB  - OBJECTIVES: To determine the level of iodine in the salt at the retail shop and
      consumption levels and assess the knowledge, attitude and practice (KAP) of food
      caterers and shopkeepers about iodized salt and iodine deficiency disorders
      (IDD). DESIGN: Cross-sectional community based. SETTING: Retail shops and
      households in Shebe town-Jimma zone, southwest Oromiya region. SUBJECTS: Thirty
      three shopkeepers and 299 food caterers of households in Shebe town. RESULTS: The
      iodine content of household salt samples ranged, from 0-75 PPM and that of the
      shop samples ranged from 0.1-75 PPM. Eighty one per cent of household salt
      samples and 82% of shop salt samples have iodine levels below the minimum
      standard set by the Quality and Standard Authority of Ethiopia. Knowledge about
      iodized salt was fairly lower for food caterers (21%) than shopkeepers (57.6%).
      More (80%) of shopkeepers have favourable attitude than household food caterers
      (50.6%). Improper practices of food caterers related to iodized salt were found
      to be associated with female sex (P<0.01), Amhara ethnicity (P<0.001), Orthodox
      religion (P=0.008), literacy status (P=0.04) and occupation (P=0.01). Good
      knowledge, about iodized salt was significantly associated with favourable
      attitude among food caterers (P<0.001). CONCLUSION: This study demonstrated that
      high proportions of residents in Shebe town were consuming inadequately iodized
      salt. There is a marked loss of iodine from salt by the time it reaches to
      consumption level in that some households were found to use salt with zero iodine
      content, whereas, all salt samples collected from the shops have at least some
      iodine. Poor awareness about iodized salt among food caterers and even in
      shopkeepers was also disclosed in this study. Socio-demographic factors such as
      ethnicity, religion, sex, lower educational level of food caterers might have an
      influence on poor, household practices like exposure of salt to sunlight.
      Information, education and communication on the importance consuming iodized salt
      and its proper handling in the house and regular monitoring of the salt iodine
      level at consumer level is essential for elimination of IDD.

PMID- 15250628
TI  - Comparison between sonographic and plain radiography in the diagnosis of small
      bowel obstruction at Mulago Hospital, Uganda.
AB  - OBJECTIVE: To evaluate the role of sonography compared to plain radiography in
      the diagnosis of patients with suspected small bowel obstruction as well as to
      determine their specificity, sensitivity and accuracy in the Ugandan setting.
      DESIGN: Prospective comparative study. SETTING: Mulago Hospital, Uganda's main
      referal Hospital and Makerere University Medical School. SUBJECTS: Seventy
      patients with suspected small bowel obstruction (SBO) were evaluated at Mulago
      Hospital between December 1998 and January 2000, 42 patients were males and 28
      females. Patients were aged three days to two years and had a clinical suspicion
      of SBO. RESULTS: Of the 70 patients, 55 were confirmed to have had SBO. Four had
      ileus and 11 had no SBO. Sixty four per cent were managed surgically while 36%
      were managed conservatively. Sonography made a diagnosis of SBO in 92.7% and
      detected strangulation in 71% of patients. Plain radiography made a diagnosis in
      85.5% of patients and did not detect strangulation. Specificity was 100% for
      both, sensitivity 93%, PPV 100%, NPV 73% for sonography. Sensitivity was 85%, PPV
      100%, NPV 58% for plain radiography. MAIN OUTCOME MEASURES: The accuracy of
      sonography was 93% as compared to 87% for plain radiography. The level of
      obstruction was correctly predicted in 81% by sonography and 64% with plain
      radiography. CONCLUSION: It was concluded that sonography is as accurate,
      specific and sensitive as plain radiography in the diagnosis of SBO as well as
      determining the level of obstruction in a Ugandan setting. Sonography was found
      to be more accurate at determining the cause of obstruction and detecting
      strangulation. It is recommended that sonography should be the initial imaging
      modality for patients presenting with suspected SBO and plain radiography should
      only be used as a complimentary investigation.

PMID- 15250629
TI  - Geometric measurements of the acetabulum in adult Malawians: radiographic study.
AB  - OBJECTIVES: To determine the acetabular depth as well as acetabular and centre
      edge angles; to assess the influence of sex, if any, in these geometric
      measurements; and to determine the prevalence of hip dysplasia in adult
      Malawians. DESIGN: A retrospective study. SETTING: Queen Elizabeth Central
      Hospital (QECH) and Blantyre Adventist Hospital (BAH). MAIN OUTCOME MEASURES: The
      acetabular and centre edge angles, acetabular depth and the prevalence of hip
      dysplasia were determined. MATERIALS AND METHODS: Two hundred and fifty three
      bilateral radiographs of the hip from adults, 133 men and 129 women, were used to
      measure the acetabular depth, angle and centre edge angle using a calliper and
      goniometer. The radiographs were taken from patients with no underlying bone
      disease between January 1997 and February 2001 at QECH and BAH. RESULTS: The
      prevalence of hip dysplasia was 11.54% for men and 13.16% for women with respect
      to centre edge angles but this difference by sex was not significant (P>0.1).
      However, the prevalence of hip dysplasia with respect to centre edge angle showed
      significantly more dysplasia in Malawian men than Nigerian and Chinese men
      (P<0.001 and P<0.05, respectively). Centre edge angles also showed a wider range
      in Malawian men (19-51 degrees right, and 15-52 degrees left) than women (18-45
      degrees right, 20-46 degrees left). In both hips, the acetabular angles were more
      obtuse in men (35.52 degrees right, 34.21 degrees left) than women (29.43 degrees
      right, 29.29 degrees left), and this difference was significant (P<0.001). The
      ranges of acetabular angles were wider in women (11-38 degrees right, 8-40
      degrees left) than men (24-49 degrees right, 20-40 degrees left). Acetabular
      depth was also greater in men than in women (P<0.01 right hip, P<0.02 left hip).
      CONCLUSION: Sex influences geometrical measurements of the acetabulum. The
      prevalence of hip dysplasia with respect to centre edge angle was significantly
      higher in women than men and the prevalence for men with respect to centre edge
      angle was significantly different when compared with Nigerian and Chinese men.
      This information will assist clinicians in the region and Malawi in particular to
      interpret hip X-rays of African patients.

PMID- 15250630
TI  - Disseminated cryptosporidiosis in Turkey: case report.
AB  - Cryptosporidium sp is a protozoan that displays an intracellular settlement
      primarily in the intestinal systems of humans and can result in diarrhoea.
      Undernourished children and persons with immunosuppression in developing
      countries are especially vulnerable to infection with this parasite. A 12-month
      old female presented at Ege University, Faculty of Medicine, Department of
      Paediatrics with complaints of fever, diarrhoea, respiratory distress and growth
      development retardation was diagnosed with CD40 deficiency (Hyper IgM Type 3).
      During the one year investigation process of the case with chronic diarrhoea and
      necrotic pneumonia, Cryptosporidium sp oocysts were found in nine of the 22
      faecal examinations and also in transtracheal aspiration liquid examined using
      the Kinyoun Acid-fast staining method. In conclusion, it is thought that
      cryptosporidiosis should also be considered in the distinct diagnosis of
      immunodeficient infants who are presented with respiratory and gastrointestinal
      system complaints.

PMID- 15250631
TI  - Quantitative evaluation of image-based distortion correction in diffusion tensor
      imaging.
AB  - A statistical method for the evaluation of image registration for a series of
      images based on the assessment of consistency properties of the registration
      results is proposed. Consistency is defined as the residual error of the
      composition of cyclic registrations. By combining the transformations of
      different algorithms the consistency error allows a quantitative comparison
      without the use of ground truth, specifically, it allows a determination as to
      whether the algorithms are compatible and hence provide comparable registrations.
      Consistency testing is applied to evaluate retrospective correction of eddy
      current-induced image distortion in diffusion tensor imaging of the brain. In the
      literature several image transformations and similarity measures have been
      proposed, generally showing a significant reduction of distortion in side-by-side
      comparison of parametric maps before and after registration. Transformations
      derived from imaging physics and a three-dimensional affine transformation as
      well as mutual information (MI) and local correlation (LC) similarity are
      compared to each other by means of consistency testing. The dedicated
      transformations could not demonstrate a significant difference for more than half
      of the series considered. LC similarity is well-suited for distortion correction
      providing more consistent registrations which are comparable to MI.

PMID- 15250632
TI  - Thickness correction of mammographic images by means of a global parameter model
      of the compressed breast.
AB  - Peripheral enhancement and tilt correction of unprocessed digital mammograms was
      achieved with a new reversible algorithm. This method has two major advantages
      for image visualization. First, the display dynamic range can be relatively
      small, and second, adjustment of the overall luminance to inspect details is not
      required in most cases. The correction is useful for preprocessing in computer
      aided detection/diagnosis algorithms. The method is based on knowledge of the
      three-dimensional compressed breast shape to equalize thickness by adding virtual
      tissue, which results in intensity equalization for the mammographic image.
      Previously described methods implicitly estimate the contribution of thickness
      variations to image intensity, usually by nonparametric methods. The proposed
      method employs a global parametic breast shape model, which is advantageous for
      visualization and CAD.

PMID- 15250633
TI  - Automatic identification of bacterial types using statistical imaging methods.
AB  - The objective of the current study is to develop an automatic tool to identify
      microbiological data types using computer-vision and statistical modeling
      techniques. Bacteriophage (phage) typing methods are used to identify and extract
      representative profiles of bacterial types out of species such as the
      Staphylococcus aureus. Current systems rely on the subjective reading of profiles
      by a human expert. This process is time-consuming and prone to errors, especially
      as technology is enabling the increase in the number of phages used for typing.
      The statistical methodology presented in this work, provides for an automated,
      objective and robust analysis of visual data, along with the ability to cope with
      increasing data volumes.

PMID- 15250634
TI  - Reconstructions of chest phantoms by the D-bar method for electrical impedance
      tomography.
AB  - The problem this paper addresses is how to use the two-dimensional D-bar method
      for electrical impedance tomography with experimental data collected on finitely
      many electrodes covering a portion of the boundary of a body. This requires an
      approximation of the Dirichlet-to-Neumann, or voltage-to-current density map,
      defined on the entire boundary of the region, from a finite number of matrix
      elements of the current-to-voltage map. Reconstructions from experimental data
      collected on a saline filled tank containing agar heart and lung phantoms are
      presented, and the results are compared to reconstructions by the NOSER algorithm
      on the same data.

PMID- 15250635
TI  - Statistical estimation of resistance/conductance by electrical impedance
      tomography measurements.
AB  - This paper is built upon the assumption that in electrical impedance tomography,
      vectors of voltages and currents are linearly dependent through a resistance
      matrix. This linear relationship was confirmed experimentally and may be derived
      analytically under certain assumptions regarding electrodes (Isaacson, 1991).
      Given measurement data consisting of voltages and currents, we treat this
      relationship as a linear statistical model. Thus, our goal is not to reconstruct
      the image but directly estimate its electromagnetic properties reflected in the
      resistance and/or conductance matrix using electrical impedance tomography (EIT)
      measurements of voltages and currents on the periphery of the body. Since no
      inverse problem is involved the algorithm for estimation merely reduces to one
      matrix inversion. We estimate the impedance resistance matrix using well
      established statistical inference techniques for linear regression models. We
      provide a comprehensive treatment for a two-dimensional homogeneous body of a
      circular shape, by which many concepts of electrical impedance tomography, such
      as width of electrodes, the difference between voltage-current and current
      voltage systems are illustrated. Our theory may be applied to various tests
      including EIT hardware calibration and whether the medium is homogeneous. These
      tests are illustrated on phantom agar data.

PMID- 15250636
TI  - A method of generalized projections (MGP) ghost correction algorithm for
      interleaved EPI.
AB  - Investigations into the method of generalized projections (MGP) as a ghost
      correction method for interleaved EPI are described. The technique is image-based
      and does not require additional reference scans. The algorithm was found to be
      more effective if a priori knowledge was incorporated to reduce the degrees of
      freedom, by modeling the ghosting as arising from a small number of phase
      offsets. In simulations with phase variation between consecutive shots for n
      interleaved echo planar imaging (EPI), ghost reduction was achieved for n = 2
      only. With no phase variation between shots, ghost reduction was obtained with n
      up to 16. Incorporating a relaxation parameter was found to improve convergence.
      Dependence of convergence on the region of support was also investigated. A fully
      automatic version of the method was developed, using results from the
      simulations. When tested on in vivo 2-, 16-, and 32-interleaved spin-echo EPI
      data, the method achieved deghosting and image restoration close to that obtained
      by both reference scan and odd/even filter correction, although some residual
      artifacts remained.

PMID- 15250637
TI  - Robust real-time myocardial border tracking for echocardiography: an information
      fusion approach.
AB  - Ultrasound is a main noninvasive modality for the assessment of the heart
      function. Wall tracking from ultrasound data is, however, inherently difficult
      due to weak echoes, clutter, poor signal-to-noise ratio, and signal dropouts. To
      cope with these artifacts, pretrained shape models can be applied to constrain
      the tracking. However, existing methods for incorporating subspace shape
      constraints in myocardial border tracking use only partial information from the
      model distribution, and do not exploit spatially varying uncertainties from
      feature tracking. In this paper, we propose a complete fusion formulation in the
      information space for robust shape tracking, optimally resolving uncertainties
      from the system dynamics, heteroscedastic measurement noise, and subspace shape
      model. We also exploit information from the ground truth initialization where
      this is available. The new framework is applied for tracking of myocardial
      borders in very noisy echocardiography sequences. Numerous myocardium tracking
      experiments validate the theory and show the potential of very accurate wall
      motion measurements. The proposed framework outperforms the traditional shape
      space-constrained tracking algorithm by a significant margin. Due to the optimal
      fusion of different sources of uncertainties, robust performance is observed even
      for the most challenging cases.

PMID- 15250638
TI  - Three-dimensional myocardial strain reconstruction from tagged MRI using a
      cylindrical B-spline model.
AB  - In this paper, we present a new method for reconstructing three-dimensional (3-D)
      left ventricular myocardial strain from tagged magnetic resonance (MR) image data
      with a 3-D B-spline deformation model. The B-spline model is based on a
      cylindrical coordinate system that more closely fits the morphology of the
      myocardium than previously proposed Cartesian B-spline models and does not
      require explicit regularization. Our reconstruction method first fits a spatial
      coordinate B-spline displacement field to the tag line data. This displacement
      field maps each tag line point in the deformed myocardium back to its reference
      position (end-diastole). The spatial coordinate displacement field is then
      converted to material coordinates with another B-spline fit. Finally, strain is
      computed by analytically differentiating the material coordinate B-spline
      displacement field with respect to space. We tested our method with strains
      reconstructed from an analytically defined mathematical left ventricular
      deformation model and ten human imaging studies. Our results demonstrate that a
      quadratic cylindrical B-spline with a fixed number of control points can
      accurately fit a physiologically realistic range of deformations. The average 3-D
      reconstruction computation time is 20 seconds per time frame on a 450 MHz Sun
      Ultra80 workstation.

PMID- 15250639
TI  - Estimating topology preserving and smooth displacement fields.
AB  - We propose a method for enforcing topology preservation and smoothness onto a
      given displacement field. We first analyze the conditions for topology
      preservation on two- and three-dimensional displacement fields over a discrete
      rectangular grid. We then pose the problem of finding the closest topology
      preserving displacement field in terms of its complete set of gradients, which we
      later solve using a cyclic projections framework. Adaptive smoothing of a
      displacement field is then formulated as an extension of topology preservation,
      via constraints imposed on the Jacobian of the displacement field. The simulation
      results indicate that this technique is a fast and reliable method to estimate a
      topology preserving displacement field from a noisy observation that does not
      necessarily preserve topology. They also show that the proposed smoothing method
      can render morphometric analysis methods that are based on displacement field of
      shape transformations more robust to noise without removing important morphologic
      characteristics.

PMID- 15250640
TI  - Time delay for arrival of MR contrast agent in collateral-dependent myocardium.
AB  - An analysis of the kinetics of myocardial contrast enhancement is an important
      component of myocardial perfusion studies. The contrast enhancement can be
      modeled by a linear time-invariant system, and the myocardial impulse response,
      calculated by deconvolution of the measured tissue response with an arterial
      input, gives a direct estimate of myocardial blood flow. In this paper, we
      analyze the effects of delays in the contrast enhancement, that occur in
      collateral-dependent myocardium, where the tracer reaches the tissue region only
      through branches from other coronary arteries that form natural bypass vessels.
      We investigate how the delayed arrival of tracer alters the myocardial impulse
      response. Model-independent deconvolution is applied to determine the lag between
      arterial input and tissue enhancement. Experimental data in a porcine model of
      collateral development indicate that the delayed arrival of an injected tracer,
      measured at rest, is a useful marker to identify collateral-dependent myocardium,
      and predict its flow capacitance.

PMID- 15250641
TI  - Ideal observers and optimal ROC hypersurfaces in N-class classification.
AB  - The likelihood ratio, or ideal observer, decision rule is known to be optimal for
      two-class classification tasks in the sense that it maximizes expected utility
      (or, equivalently, minimizes the Bayes risk). Furthermore, using this decision
      rule yields a receiver operating characteristic (ROC) curve which is never above
      the ROC curve produced using any other decision rule, provided the observer's
      misclassification rate with respect to one of the two classes is chosen as the
      dependent variable for the curve (i.e., an "inversion" of the more common
      formulation in which the observer's true-positive fraction is plotted against its
      false-positive fraction). It is also known that for a decision task requiring
      classification of observations into N classes, optimal performance in the
      expected utility sense is obtained using a set of N-1 likelihood ratios as
      decision variables. In the N-class extension of ROC analysis, the ideal observer
      performance is describable in terms of an (N2-N-1)-parameter hypersurface in an
      (N2-N)-dimensional probability space. We show that the result for two classes
      holds in this case as well, namely that the ROC hypersurface obtained using the
      ideal observer decision rule is never above the ROC hypersurface obtained using
      any other decision rule (where in our formulation performance is given
      exclusively with respect to between-class error rates rather than within-class
      sensitivities).

PMID- 15250642
TI  - A modified uniform Cramer-Rao bound for multiple pinhole aperture design.
AB  - This paper presents a modified Uniform Cramer-Rao bound (UCRB) for studying
      estimator spatial resolution and variance tradeoffs. We proposed to use a
      resolution constraint that is imposed on mean gradient vectors of achieved
      estimators and derived the minimum achievable variance for any estimator
      satisfies this resolution constraint. This approach partially overcomes the
      limitations of the former UCRB approach based on a bias-gradient norm constraint.
      We applied this method in a feasibility study of using multiple pinhole apertures
      for small animal SPECT imaging applications. The SPECT system studied was based
      on an existing gamma camera. The achievable spatial resolution and variance
      tradeoffs for systems with different design parameters, such as number of
      pinholes and pinhole size, were studied.

PMID- 15250644
TI  - Registration-based interpolation.
AB  - A method is presented to interpolate between neighboring slices in a grey-scale
      tomographic data set. Spatial correspondence between adjacent slices is
      established using a nonrigid registration algorithm based on B-splines which
      optimizes the normalized mutual information similarity measure. Linear
      interpolation of the image intensities is then carried out along the directions
      calculated by the registration algorithm. The registration-based method is
      compared to both standard linear interpolation and shape-based interpolation in
      20 tomographic data sets. Results show that the proposed method statistically
      significantly outperforms both linear and shape-based interpolation.

PMID- 15250643
TI  - Simultaneous truth and performance level estimation (STAPLE): an algorithm for
      the validation of image segmentation.
AB  - Characterizing the performance of image segmentation approaches has been a
      persistent challenge. Performance analysis is important since segmentation
      algorithms often have limited accuracy and precision. Interactive drawing of the
      desired segmentation by human raters has often been the only acceptable approach,
      and yet suffers from intra-rater and inter-rater variability. Automated
      algorithms have been sought in order to remove the variability introduced by
      raters, but such algorithms must be assessed to ensure they are suitable for the
      task. The performance of raters (human or algorithmic) generating segmentations
      of medical images has been difficult to quantify because of the difficulty of
      obtaining or estimating a known true segmentation for clinical data. Although
      physical and digital phantoms can be constructed for which ground truth is known
      or readily estimated, such phantoms do not fully reflect clinical images due to
      the difficulty of constructing phantoms which reproduce the full range of imaging
      characteristics and normal and pathological anatomical variability observed in
      clinical data. Comparison to a collection of segmentations by raters is an
      attractive alternative since it can be carried out directly on the relevant
      clinical imaging data. However, the most appropriate measure or set of measures
      with which to compare such segmentations has not been clarified and several
      measures are used in practice. We present here an expectation-maximization
      algorithm for simultaneous truth and performance level estimation (STAPLE). The
      algorithm considers a collection of segmentations and computes a probabilistic
      estimate of the true segmentation and a measure of the performance level
      represented by each segmentation. The source of each segmentation in the
      collection may be an appropriately trained human rater or raters, or may be an
      automated segmentation algorithm. The probabilistic estimate of the true
      segmentation is formed by estimating an optimal combination of the segmentations,
      weighting each segmentation depending upon the estimated performance level, and
      incorporating a prior model for the spatial distribution of structures being
      segmented as well as spatial homogeneity constraints. STAPLE is straightforward
      to apply to clinical imaging data, it readily enables assessment of the
      performance of an automated image segmentation algorithm, and enables direct
      comparison of human rater and algorithm performance.

PMID- 15250645
TI  - Expo[not-so]sure... reflections on a tricky issue in musculoskeletal research.

PMID- 15250646
TI  - Mechanical exposure concepts using force as the agent.
AB  - This paper presents a model that addresses mechanical exposure with regard to the
      development of musculoskeletal disorders, defines exposure concepts, unifies a
      variety of exposures, and includes the concept of human activity. When force is
      used as an agent, concepts related to the measurement, transformation, and
      interaction of the agent with tissues can be developed for use in epidemiologic
      exposure assessment and hazard assessment. The importance of tissue response in
      the exposure modeling process and in the creation of exposure indices is
      highlighted. Unfortunately, the response of tissue to forces of varying
      amplitudes and time variation patterns are largely unknown and thus reduce the
      possibility to develop optimal exposure assessment metrics. Although the paper
      argues that an exposure index at the tissue level may be the most powerful,
      considerations of resources and current knowledge make exposure indices based on
      external exposure or internal exposure preferable choices.

PMID- 15250647
TI  - Effects of lifestyle intervention on neck, shoulder, elbow and wrist symptoms.
AB  - OBJECTIVES: The objective of this study was to determine whether lifestyle
      intervention to control hypertension can affect neck, shoulder, elbow, and wrist
      symptoms. METHODS: In a randomized controlled trial, 731 employees from 45
      worksites were assigned for 12 months to lifestyle intervention in a
      rehabilitation center or to usual care provided by occupational or primary health
      care services. The participants had a systolic blood pressure of 140-179 mm Hg or
      a diastolic blood pressure of 90-109 mm Hg, or antihypertensive drug treatment.
      In addition to the cardiovascular risk factors, the occurrences of neck,
      shoulder, elbow, and wrist symptoms and disability during the previous 12 months
      were recorded before the intervention and 1 year later. RESULTS: The reported
      disability due to neck pain during the previous 12 months fell significantly more
      (-7%) in the intervention group than in the group in usual care (-2%). The
      perceived shoulder pain during the previous 7 days also decreased significantly
      more in the intervention group than in the control group among the women (net
      change 16%) and among the participants who were more highly physically active
      (net change 10%). Weight, body mass index, and waist and hip circumferences
      decreased, and physical activity increased, substantially more in the
      intervention group. The changes in elbow or wrist pain and related disability did
      not differ significantly between the intervention and control groups.
      CONCLUSIONS: Lifestyle intervention to control hypertension has a favorable
      impact on perceived disability due to neck pain.

PMID- 15250648
TI  - Costs of occupational injury and illness across industries.
AB  - OBJECTIVES: This study has ranked industries using estimated total costs and
      costs per worker. METHODS: This incidence study of nationwide data was carried
      out in 1993. The main outcome measure was total cost for medical care, lost
      productivity, and pain and suffering for the entire United States (US). The
      analysis was conducted using fatal and nonfatal injury and illness data recorded
      in large data sets from the US Bureau of Labor Statistics. Cost data were derived
      from workers' compensation records, estimates of lost wages, and jury awards.
      Current-value calculations were used to express all costs in 1993 in US dollars.
      RESULTS: The following industries were at the top of the list for average cost
      (cost per worker): taxicabs, bituminous coal and lignite mining, logging, crushed
      stone, oil field services, water transportation services, sand and gravel, and
      trucking. Industries high on the total-cost list were trucking, eating and
      drinking places, hospitals, grocery stores, nursing homes, motor vehicles, and
      department stores. Industries at the bottom of the cost-per-worker list included
      legal services, security brokers, mortgage bankers, security exchanges, and labor
      union offices. CONCLUSIONS: Detailed methodology was developed for ranking
      industries by total cost and cost per worker. Ranking by total costs provided
      information on total burden of hazards, and ranking by cost per worker provided
      information on risk. Industries that ranked high on both lists deserve increased
      research and regulatory attention.

PMID- 15250649
TI  - Factors associated with early-stage pulmonary fibrosis as determined by high
      resolution computed tomography among persons occupationally exposed to asbestos.
AB  - OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early
      stages. The aim of this study was to determine criteria for independently
      associated features of pulmonary fibrosis in high-resolution computed tomograms
      among persons occupationally exposed to asbestos. METHODS: Retired persons with
      documented occupational asbestos exposure and no known asbestos-related diseases
      were assessed for occupational, clinical, functional respiratory, and chest X-ray
      criteria. In addition, they all underwent high-resolution computed tomography
      (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled
      participants had features of pulmonary fibrosis consistent with asbestosis in the
      HRCT. Among those with small irregular opacities of <1/0 according to the 1980
      International Labour Office Classification (ILO-C) in their X-rays, 5% had
      asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per
      year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index
      (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x
      years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C
      (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No
      combinations of these criteria simultaneously yielded high sensitivity and
      specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2%
      of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the
      finding confirming the low incidence of asbestosis for such low exposure, as
      previously reported on the basis of X-ray data. CONCLUSIONS: Additional research
      is needed to better identify the persons most likely to benefit from HRCT
      screening for asbestosis.

PMID- 15250650
TI  - Occupation, pesticide exposure and risk of multiple myeloma.
AB  - OBJECTIVES: This population-based case-control study examined the relationship
      between occupation, living or working on a farm, pesticide exposure, and the risk
      of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with
      myeloma and 2131 controls. Information was obtained on sociodemographic factors,
      occupational history, and history of living and working on a farm. Occupational
      and industrial titles were coded by standardized classification systems. A job
      exposure matrix was developed for occupational pesticide exposure. Odds ratios
      (OR) and 95% confidence intervals (95% CI) were estimated by unconditional
      logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9
      (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7
      (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no
      increased risks were found for cattle, beef, pig, or chicken farm residents or
      workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI
      0.9-1.8). Significantly increased risks were found for pharmacists, dieticians
      and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI
      1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR
      10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8),
      and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest
      increased risk of multiple myeloma is suggested for occupational pesticide
      exposure. The increased risk for sheep farm residents or workers indicates that
      certain animal viruses may be involved in myeloma risk.

PMID- 15250651
TI  - Scientific production and international collaboration in occupational health,
      1992-2001.
AB  - OBJECTIVES: The objectives of the present study were twofold, to describe
      international scientific production in occupational health and to examine
      international collaboration in this discipline. METHODS: A bibliometric study was
      carried out, using Science Citation Index, in order to evaluate the articles
      published during the period 1992-2001 in eight representative occupational health
      journals. Scientific production, collaborative profiles for each country, and the
      significant relationships established between countries are reported. RESULTS:
      One or more institutions in the United States had contributed to over 40% of the
      articles examined. The United States was followed by the United Kingdom (9.15%)
      and then Sweden (8.65%). When population size effects were eliminated, the
      Scandinavian countries proved to be the leading producers. After correction for
      gross domestic product, there was an increase in the ranking of apparently
      scientifically modest countries. The Scandinavian countries remained high. In
      terms of international collaboration in general, there was an inverse
      relationship between the production of a country and the proportion of articles
      co-authored with institutions in other countries. Finally, the significant
      relationships between countries permitted the identification of up to six large
      collaboration nuclei. CONCLUSIONS: The high absolute and relative Scandinavian
      production is suggestive of the great importance of occupational health in these
      countries. Access to publication by more modest countries, scientifically
      speaking, is observed to occur through collaboration with the high-production
      countries. In this sense, it would seem necessary to study the basis underlying
      these relationships. Finally, the characterization of the collaborative nuclei
      does not differ greatly from what was expected.

PMID- 15250652
TI  - Incidence of ulnar nerve entrapment at the elbow in repetitive work.
AB  - OBJECTIVES: Despite the high frequency of work-related musculoskeletal disorders,
      the relation between work conditions and ulnar nerve entrapment at the elbow has
      not been the object of much research. In the present study, the predictive
      factors for such ulnar nerve entrapment were determined in a 3-year prospective
      survey of upper-limb work-related musculoskeletal disorders in repetitive work.
      METHODS: In 1993-1994 and 3 years later, 598 workers whose jobs involved
      repetitive work underwent an examination by their occupational health physicians
      and completed a self-administered questionnaire. Predictive factors associated
      with the onset of ulnar nerve entrapment at the elbow were studied with bivariate
      and multivariate analyses. RESULTS: The annual incidence was estimated at 0.8%
      per person-year, on the basis of 15 new cases during the 3-year period. Holding a
      tool in position was the only predictive biomechanical factor [odds ratio (OR)
      4.1, 95% confidence interval (95% CI) 1.4-12.0]. Obesity increased the risk of
      ulnar nerve entrapment at the elbow (OR 4.3, 95% CI 1.2-16.2), as did the
      presence of medial epicondylitis, carpal tunnel syndrome, radial tunnel syndrome,
      and cervicobrachial neuralgia. The associations with "holding a tool in position"
      and obesity were unchanged when the presence of other diagnoses was taken into
      account. CONCLUSIONS: Despite the limitations of the study, the results suggest
      that the incidence of ulnar nerve entrapment at the elbow is associated with one
      biomechanical risk factor (holding a tool in position, repetitively), overweight,
      and other upper-limb work-related musculoskeletal disorders, especially medial
      epicondylitis and other nerve entrapment disorders (cervicobrachial neuralgia and
      carpal and radial tunnel syndromes).

PMID- 15250653
TI  - Exposure assessment for a population-based case-control study combining a job
      exposure matrix with interview data.
AB  - OBJECTIVES: A system that combines the ease of use of a job-exposure matrix while
      taking into account job-specific data is needed. This study aimed to produce a
      detailed method for combining interview data with expert assessments for a large
      population-based case-control study of Parkinson's disease. METHOD: An interview
      administered core questionnaire with a series of questions that triggers
      substance-specific questionnaires to gather information on key parameters is
      administered. Using a job-exposure matrix to generate base estimates, assessors
      can modify this estimate of exposure intensity using worker-specific data such as
      the use of control measures, reports of substance-specific acute symptoms, and
      the quantity of material being processed. Detailed guidance for making
      adjustments to exposure estimates for these modifiers is presented. RESULTS: The
      method has been partially validated through the use of a comparison of estimates
      for a separate cohort with previously validated exposure reconstructions.
      Agreement was high, with a Spearman's rho of 0.89 (P < 0.01). The results from a
      quality assurance system employed as part of the methodology show a high degree
      of repeatability in generated exposure values both over time (Spearman's rho
      0.98, P < 0.01) and between different assessors (Spearman's rho 0.88, P < 0.01).
      CONCLUSIONS: The method provides detailed quantitative exposure indices for
      occupational epidemiology. It has particular strengths both in terms of ease and
      speed of use. It is hoped that it will provide a useful structure for future
      epidemiologic work.

PMID- 15250654
TI  - Mortality from chronic obstructive pulmonary disease and pleural mesothelioma in
      an area contaminated by natural fiber (fluoro-edenite).
AB  - OBJECTIVES: The purpose of the present study was to investigate the association
      between mortality from chronic obstructive pulmonary disease (COPD) and exposure
      to fluoro-edenite, a newly discovered amphibolic fiber found in Biancavilla
      (Sicily), a municipality on the slope of the Etna volcano, where a high mortality
      from malignant mesothelioma had been previously observed. METHODS: Thirty-six
      municipalities located in the volcanic area of mount Etna were selected for
      study. An ecological regression model was applied with mortality from COPD as the
      dependent variable, mortality from mesothelioma as a proxy for exposure to fluoro
      edenite, and lung cancer mortality, an urban-rural index, a deprivation index and
      an aging index as the predictors of COPD mortality. For each municipality, risk
      classes were determined for the continuous variables with the use of a finite
      mixture model. RESULTS: A significant association was found between COPD
      mortality and pleural neoplasm mortality among the women in this study. The
      association was less consistent for the men. CONCLUSIONS: Despite the limitations
      of this ecological study, the results cohere with the results of toxicologic and
      observational studies and suggest an etiologic role for fluoro-edenite in
      nonmalignant respiratory diseases.

PMID- 15250655
TI  - Neuropathy in grout workers.

PMID- 15250656
TI  - Genetics and epidemiology.

PMID- 15250657
TI  - Joseph Priestley (1733-1804).

PMID- 15250658
TI  - Pointing out of the picture.
AB  - The eyes of portrayed people are often noticed to 'follow you' when you move with
      respect to a flat painting or photograph. We investigated this well-known effect
      through extensive measurements of pictorial relief and apparent orientation of
      the picture surface for a number of viewing conditions, including frontal and
      oblique views. We conclude that cases of both oblique and frontal viewing are
      very similar in that perception simply follows what is indicated by the proximal
      stimulus, even though this may imply that the (perceived) physical and pictorial
      spaces segregate. The effect of foreshortening then causes an apparent narrowing
      of pictorial objects. We find no evidence for any 'correction' mechanisms that
      might be specifically active in oblique viewing conditions.

PMID- 15250659
TI  - Ambiguous figures: living versus nonliving objects.
AB  - Eleven series of figures were studied, each series ranging from one extreme
      interpretation via five ambiguous intermediates to a second extreme
      interpretation. Triplets consisting of an ambiguous exemplar in the middle
      flanked on the left and right by its two extreme interpretations were presented
      to large groups of subjects. The initial aim was to establish the levels of
      perceptual ambiguity of each exemplar in a series, and normative data on the
      ambiguous figures are provided for future reference and use. However, several
      biases were encountered and these were examined in more detail. In experiment 1
      the subject's task was to compare the middle figure with the flankers and draw an
      arrow from the middle figure towards the flanking extreme they judged the most
      similar. Here, an overall preference for the left extreme was found. Therefore
      the instructions were reversed in experiment 2; flankers had to be compared with
      the middle figure. The preference for the left extreme remained for figures of
      living objects, but for nonliving objects the preference switched to the right
      extreme. To do away with any effect of the arrows, in experiment 3 subjects were
      divided into two groups each receiving different instructions and were asked to
      circle one of the extremes. However, the pattern of biases remained the same. The
      bias found with figures of living objects may be explained on the basis of top
      down processes. For nonliving figures, an hypothesis based on bottom-up processes
      like neural fatigue was considered but rejected.

PMID- 15250660
TI  - Bistability and biasing effects in the perception of ambiguous point-light
      walkers.
AB  - The perceptually bistable character of point-light walkers has been examined in
      three experiments. A point-light figure without explicit depth cues constitutes a
      perfectly ambiguous stimulus: from all viewpoints, multiple interpretations are
      possible concerning the depth orientation of the figure. In the first experiment,
      it is shown that non-lateral views of the walker are indeed interpreted in two
      orientations, either as facing towards the viewer or as facing away from the
      viewer, but that the interpretation in which the walker is oriented towards the
      viewer is reported more frequently. In the second experiment the point-light
      figure was walking backwards, making the global orientation of the point-light
      figure opposite to the direction of global motion. The interpretation in which
      the walker was facing the viewer was again reported more frequently. The
      robustness of these findings was examined in the final experiment, in which the
      effects of disambiguating the stimulus by introducing a local depth cue
      (occlusion) or a more global depth cue (applying perspective projection) were
      explored.

PMID- 15250661
TI  - Distance estimation in a dynamic simulated environment: a visual field dependence
      problem?
AB  - Egocentric distance estimation implies that the subject perceives his own
      location in the environment. In a simulated environment, subjects have to
      transpose perceptively their own observation point in order to assume their
      virtual body position. As only visual information specifies this position, their
      ability to perceive the camera viewpoint should be linked to the field dependence
      independence factor (FDI). Field-independent subjects underestimated the mid
      distance between their own virtual body position and a far-located target; their
      bisection was located between the projective (2-D) and the simulated (3-D) mid
      distance which indicates their difficulty in considering the in-depth simulated
      spatial references. High correlations between the vertical estimation in the rod
      and-frame test and the egocentric-distance-estimation task (with shifted camera)
      suggest a similar perceptive process in both tasks. This result is confirmed by
      the better performances of the field-dependent subjects in this condition. In
      conclusion, we discuss the relationship between FDI and the sense of presence in
      virtual environments.

PMID- 15250662
TI  - When facial attractiveness is only skin deep.
AB  - Whilst the relationship between aspects of facial shape and attractiveness has
      been extensively studied, few studies have investigated which characteristics of
      the surface of faces positively influence attractiveness judgments. As many
      researchers have proposed a link between attractiveness and traits that appear
      healthy, apparent health of facial skin might be a property of the surface of
      faces that positively influences attractiveness judgments. In experiment 1 we
      tested for a positive correlation between ratings of the apparent health of small
      skin patches (extracted from the left and right cheeks of digital face images)
      and ratings of the attractiveness of male faces. By using computer-graphics
      faces, in experiment 2 we aimed to establish if apparent health of skin
      influences male facial attractiveness independently of shape information. Results
      suggest that apparent health of facial skin is correlated both with ratings of
      male facial attractiveness (experiment 1) and with being a visual cue for
      judgments of the attractiveness of male faces (experiment 2). These findings
      underline the importance of controlling for the influence of visible skin
      condition in studies of facial attractiveness and are consistent with the
      proposal that attractive physical traits are those that positively influence
      others' perceptions of an individual's health.

PMID- 15250663
TI  - Perceiving distance: a role of effort and intent.
AB  - Perceiving egocentric distance is not only a function of the optical variables to
      which it relates, but also a function of people's current physiological potential
      to perform intended actions. In a set of experiments, we showed that, as the
      effort associated with walking increases, perceived distance increases if the
      perceiver intends to walk the extent, but not if the perceiver intends to throw.
      Conversely, as the effort associated with throwing increases, perceived distance
      increases if people intend to throw to the target, but not if they intend to
      walk. Perceiving distance combines the geometry of the world with our behavior
      goals and the potential of our body to achieve these goals.

PMID- 15250664
TI  - Representational momentum in spatial hearing.
AB  - The final position of a moving visual object usually appears to be displaced in
      the direction of motion. We investigated this phenomenon, termed representational
      momentum, in the auditory modality. In a dark anechoic environment, an acoustic
      target (continuous noise or noise pulses) moved from left to right or from right
      to left along the frontal horizontal plane. Listeners judged the final position
      of the target using a hand pointer. Target velocity was 8 degrees s(-1) or 16
      degrees s(-1). Generally, the final target positions were localised as displaced
      in the direction of motion. With presentation of continuous noise, target
      velocity had a strong influence on mean displacement: displacements were stronger
      with lower velocity. No influence of sound velocity on displacement was found
      with motion of pulsed noise. Although these findings suggest that the underlying
      mechanisms may be different in the auditory and visual modality, the occurrence
      of displacements indicates that representational-momentum-like effects are not
      restricted to the visual modality, but may reflect a general phenomenon with
      judgments of dynamic events.

PMID- 15250665
TI  - Perceptual grouping in shape from shading.
AB  - We report on the reversal of asymmetry in visual-search tasks with shaded items.
      Previous studies have suggested that the target of a bottom-lit disk among
      distractors of top-lit disks is detected in a rapid and parallel manner, but not
      vice versa. However, in this study, we have shown that the compound items of top
      lit disks were searched more quickly than those composed of bottom-lit disks
      where the items had to be segregated from their background. By modulating the
      inter-element distances, we confirmed that the reversal of search asymmetry
      cannot be due to the grouping of items. Further, we showed that the regions of
      the top-lit disks were perceived as figure more consistently than those of bottom
      lit disks. The results indicate that the boundary assignment to the compound
      items of the top-lit disks enhances the segregation of search items from the
      background, and that the search mechanism may access the relatively higher
      representation that includes figure-ground relations.

PMID- 15250666
TI  - Is there an assignment of top and bottom during symmetry perception?
AB  - We report data from a discrimination task in which participants had to decide
      whether a single-item display was either vertically symmetric or asymmetric. This
      decision was found to be easier when items with a top bottom polarity were placed
      in an orientation where the wide end was the base of the stimulus and the narrow
      end was the top. The difference in reaction times between this orientation and
      its inversion was about 10 ms. We suggest that top and bottom labels are assigned
      to stimuli during the detection of bilateral symmetry.

PMID- 15250667
TI  - The modulation of the flash-lag effect by voluntary attention.
AB  - In the flash-lag effect (FLE), a flashing object appears to lag behind a moving
      object when both happen to be physically aligned to each other. According to an
      earlier account of the FLE (Baldo and Klein 1995 Nature 378 565-566), this
      perceptual phenomenon would result from differential delays in the perceptual
      processing of moving and flashing stimuli, presumably involving attentional
      mechanisms. Here, we have attempted to demonstrate in a more convincing way the
      participation of voluntary attention as a major component of the FLE. In
      experiment 1 the observer's attentional set was induced by the spatial
      probability structure of the visual stimulus. A flashing dot (relative to which
      the location of a moving dot should be judged) was presented, in separate blocks,
      at fixed, alternating, or randomly chosen locations. The two former conditions,
      providing a higher spatial predictability, yielded a smaller FLE than the latter
      condition, which provided a lower spatial predictability of the flashing dot. In
      experiment 2 we employed a standard cueing procedure, in which a participant was
      instructed to shift covertly his/her attentional focus according to a symbolic
      cue. The cue indicated, with a validity of 80%, the visual hemifield at which the
      flashing dot would be presented. As predicted by our conceptual model, the mean
      magnitude of the FLE in the valid trials was significantly smaller than that
      found in the invalid ones. Therefore, both experiments provided strong evidence
      supporting the participation of voluntary attention in the FLE. Attentional
      mechanisms should be seen not as the primary cause of the FLE, but rather as an
      important modulatory component of a broader process whose spatiotemporal dynamics
      engenders the FLE and possibly other related phenomena. Even though we elected an
      account based on the influence of attention on perceptual latencies, our
      empirical findings are compatible with other theoretical models embraced by the
      current flash-lag controversy and should be accommodated by every attempt to
      explain this perceptual phenomenon.

PMID- 15250668
TI  - Antibacterial activity of a new, stable, aqueous extract of allicin against
      methicillin-resistant Staphylococcus aureus.
AB  - The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      in hospitals and the community has led to a demand for new agents that could be
      used to decrease the spread of these bacteria. Topical agents such as mupirocin
      have been used to reduce nasal carriage and spread and to treat skin infections;
      however, resistance to mupirocin in MRSAs is increasing. Allicin is the main
      antibacterial agent isolated from garlic, but natural extracts can be unstable.
      In this study, a new, stable, aqueous extract of allicin (extracted from garlic)
      is tested on 30 clinical isolates of MRSA that show a range of susceptibilities
      to mupirocin. Strains were tested using agar diffusion tests, minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC). Diffusion tests
      showed that allicin liquids produced zone diameters >33 mm when the proposed
      therapeutic concentration of 500 microg/mL (0.0005% w/v) was used. The selection
      of this concentration was based on evidence from the MIC, MBC and agar diffusion
      tests in this study. Of the strains tested, 88% had MICs for allicin liquids of
      16 microg/mL, and all strains were inhibited at 32 microg/mL. Furthermore, 88% of
      clinical isolates had MBCs of 128 microg/mL, and all were killed at 256
      microg/mL. Of these strains, 82% showed intermediate or full resistance to
      mupirocin; however, this study showed that a concentration of 500 microg/mL in an
      aqueous cream base was required to produce an activity equivalent to 256
      microg/mL allicin liquid.

PMID- 15250669
TI  - In vitro susceptibility of Blastocystis hominis isolated from patients with
      irritable bowel syndrome.
AB  - This study aims to determine the growth pattern and in vitro susceptibility of
      clinical isolates of Blastocystis hominis to different concentrations of
      metronidazole, furazolidone and ciprofloxacin. Stool specimens from 25
      consecutive patients with irritable bowel syndrome presenting to the
      gastroenterology department of Aga Khan University Hospital between January and
      May 2003 are examined by microscopy and cultured for B. hominis. Drug
      susceptibility assays are performed for metronidazole, furazolidone, and
      ciprofloxacin using final concentrations of 0.01 mg/mL and 0.1 mg/mL. The effect
      of the drugs is assessed after B. hominis culture for 48 h. With furazolidone and
      metronidazole, 68% (17/25) and 60% (15/25) of B. hominis isolates, respectively,
      failed to grow at drug concentrations of both 0.01 mg/mL and 0.1 mg/mL. However,
      ciprofloxacin failed to suppress growth completely at both concentrations. B.
      hominis resistance to furazolidone, metronidazole and ciprofloxacin at 0.01 mg/mL
      was 32% (8/25), 40% (10/25) and 100% (25/25), respectively. B. hominis isolates
      varied in their degree of susceptibility to the three drugs studied, being
      greater with furazolidone than with metronidazole, and complete resistance with
      ciprofloxacin.

PMID- 15250670
TI  - Role of plasma homocysteine and lipoprotein (a) in coronary artery disease.
AB  - This study looks at the possible role of some non-traditional risk factors for
      premature coronary artery disease (CAD) and assesses the presence of relationship
      between these factors and the traditional cardiovascular risk factors. The study
      subjects (n=45) are divided into three groups comprising 15 premature CAD
      patients without traditional cardiovascular risk factors (group I); 15 premature
      CAD patients with one or more traditional cardiovascular risk factors (group II);
      and 15 healthy normal control subjects matched for age and sex (group III).
      Estimation of plasma homocysteine (Hcy) and plasminogen activator inhibitor-1
      (PAI-1) is performed by enzyme-linked immunosorbent assay (ELISA); plasma folic
      acid by radioimmunoassay; plasma lipoprotein a (Lpa) by turbidimetry; and plasma
      lipids by colorimetry. Results showed a significant association between elevated
      Hcy and low folate levels and premature CAD in both patient groups. Also, a
      significant association was seen between elevated PAI-1 and CAD in the two
      patient groups, and between CAD and high levels of Hcy and triglycerides, as well
      as a low level of high-density lipoprotein cholesterol. Lpa showed significant
      association with premature CAD only in group II. Thus, Hcy, folic acid and PAI-1
      might serve as independent risk factors for premature CAD in patients both with
      and without traditional coronary risk factors. However, Lpa might confer an
      additional coronary risk factor only in the presence of traditional risk factors.

PMID- 15250671
TI  - Folate and homocysteine levels in pregnancy.
AB  - This study aims to determine serum folate and plasma homocysteine levels in
      healthy pregnant women following a live birth and compare them with healthy non
      pregnant women. Fifty healthy gravid multiparous women are included in the study
      and 25 normal non-pregnant female subjects act as controls (group I). The
      pregnant women are divided into two groups according to interpregnancy interval:
      group II (six months or less); group III (18-24 months). Venous blood samples are
      analysed for red blood cell folate and homocysteine, vitamin B12, serum folate
      and albumin, and serum aminotransferases (ALT and AST). There was a significant
      decrease in red cell folate and serum folate in group II compared to the control
      group (P<0.001). Serum vitamin B12 showed no significant difference. Plasma
      homocysteine and serum albumin showed significant decreases in both groups II and
      III compared to the control group. (P<0.001) There was significant positive
      correlation between homocysteine and serum albumin in the three studied groups.
      (r=0.42, P<0.001; r=0.45, P<0.001; r=0.51, P<0.001, respectively). There was
      significant negative correlation between red cell folate and homocysteine in the
      three studied groups. (r=-0.48, P<0.001; r=-0.53, P<0.001; r=-0.49, P<0.001,
      respectively). Two cases in group II showed signs of intrauterine growth
      retardation. The results suggest that pregnant females with short interpregnancy
      intervals are more likely to develop folate deficiency. Educational strategies
      are required to increase folate awareness among women to promote the benefits of
      folic acid supplementation. Mandatory folate fortification of foods should be
      defined and monitored.

PMID- 15250672
TI  - Erythrocyte autoantibodies and expression of CD59 on the surface of red blood
      cells of polytransfused patients with beta-thalassaemia major.
AB  - Repeated transfusions for the treatment of thalassaemia major cause an insult to
      the patient's immune system and provoke post-transfusion purpura and haemolytic
      reactions that can be severe and life threatening. This study aims to investigate
      the presence of erythrocyte autoantibodies and CD59 expression on the surface of
      red blood cells (RBCs) in patients with beta-thalassaemia major, and any
      relationship to frequency of blood transfusion. The study looks at a total of 49
      patients (both children and adults) with beta-thalassaemia major, divided into
      four groups according to the number of blood transfusions received and the
      presence or absence of the spleen. Glycosylated haemoglobin, Coombs' test (direct
      and indirect) and CD59 level on the RBC surface (by flow cytometry) are estimated
      in all patients studied. Glycosylated haemoglobin level was significantly lower
      in those who had received less than 10 units of blood (group III) than in those
      who had received more than 25 units of blood and had undergone splenectomy (group
      Ib), and was significantly lower in those who had received 10-25 units of blood
      (group II) than in those that comprised group Ib (F=3.598, P=0.0205). Considering
      CD59 expression, there was a marked difference between the groups. Expression was
      highest in group III and diminished progressively through groups II, Ia
      (polytransfused, non-splenectomised) and Ib (F=19.83, P=0.0000). No relationship
      was observed between CD59 expression and either blood group or gender. A
      significant negative correlation between CD59 expression and reticulocyte
      percentage (r=-0.538, P=0.000) and normoblast count (r=-0.5455, P=0.000) was
      found. A negative correlation between lymphocytosis and CD59 expression was also
      noted in groups III (r=-0.745, P=0.013), Ia (r=-0.5849, P=0.022) and Ib (r=
      0.6711, P=0.009). Direct Coombs' test was positive in only one patient in group
      Ib, who also showed the lowest haemoglobin level. Thalassaemia patients exposed
      to multiple antigens through repeated blood transfusions showed lower CD59
      expression than did those who had received fewer transfused units, which is a
      good method of detecting potential autoantibodies. Furthermore, a negative
      Coombs' test does not exclude autoimmunisation in such patients.

PMID- 15250673
TI  - Presumptive diagnosis of brucellosis from contaminated blood cultures in an area
      of endemicity.

PMID- 15250674
TI  - Severe acquired chylomicronaemia syndrome--a challenge to the routine laboratory.

PMID- 15250675
TI  - Autoimmune haemolytic anaemia is associated with a defect in Fas-mediated
      apoptosis: a case report.

PMID- 15250676
TI  - Links between apoptosis, proliferation and the cell cycle.
AB  - Many physiological processes, including proper tissue development and
      homeostasis, require a balance between apoptosis and cell proliferation. All
      somatic cells proliferate via a mitotic process determined by progression through
      the cell cycle. Apoptosis (programmed cell death) occurs in a wide variety of
      physiological settings, where its role is to remove harmful, damaged or unwanted
      cells. Apoptosis and cell proliferation are linked by cell-cycle regulators and
      apoptotic stimuli that affect both processes. This review covers recent
      developments in the field and examines new evidence of the interconnection
      between apoptosis and cell proliferation.

PMID- 15250677
TI  - Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the
      tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia is associated with a specific translocation between
      chromosomes 9 and 22 that results in the formation of a chimaeric gene. This
      gene, when transcribed, produces the BCR-Abl oncoprotein which has tyrosine
      kinase activity and the ability to prevent apoptosis, but has no effect on
      cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript
      modelled on the ATP binding pocket of the Abl oncoprotein, prevents
      phosphorylation of effector molecules and induces apoptosis. Imatinib has limited
      effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A
      life-long regimen of imatinib should reduce the risk of relapse from cells
      leaving G0. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up
      regulation of MDR1 and over-expression of Pgp are all thought to limit the
      effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex
      mutations, which are thought to have a cumulative effect on the BCR-Abl
      oncoprotein in disrupting normal signal transduction, making these cells
      refractory to monotherapy alone. Combination therapy is thought to overcome this.
      Research studies have identified imatinib as a potential treatment option for a
      diverse range of malignancies associated with BCR-Abl, platelet-derived growth
      factor receptor (PDGFr) and c-Kit pathways. This may extend the application of
      this special therapy in the future.

PMID- 15250678
TI  - A coordination gelator that shows a reversible chromatic change and sol-gel phase
      transition behavior upon oxidative/reductive stimuli.
AB  - A novel coordination gelator exhibits reversible chromatic and sol-gel phase
      transition phenomena triggered by thermal and chemical stimuli.

PMID- 15250679
TI  - Integrated nanoreactor systems: triggering the release and mixing of compounds
      inside single vesicles.
AB  - We present a method that allows the on-demand release and mixing of zepto- to
      femtoliter volumes of solutions in the interior of vesicular nanoreactors. The
      reactors comprise a nested system of lipid vesicles, part of which release their
      cargo in the interior of the others during a thermotropic phase transition. The
      performance of individual reactors immobilized on glass is characterized using
      confocal microscopy and a fluorescent dye that reports dilution during the
      release. The results confirm the predicted temperature-induced response and
      reveal a release transition width of 3 degrees C with a half time of
      approximately 1 min.

PMID- 15250680
TI  - A simple thermodynamic test to discriminate between two-state and downhill
      folding.
AB  - The recent discovery of one-state folding, in which proteins unfold by
      progressive structural disorganizations (i.e., downhill folding), has emphasized
      the need for simple thermodynamic tests to discriminate between this behavior and
      classical two-state folding. On the basis of theoretical results from elementary
      statistical mechanical models, we propose such a test. The test involves
      monitoring the equilibrium unfolding transition induced by a combination of
      temperature and chemical denaturants with a probe that is sensitive to the
      average protein backbone conformation. The rationale is that the coupling between
      two different denaturation procedures can reveal subtle changes in protein
      conformational ensembles even when using bulk measurements. We demonstrate the
      applicability of the test by studying the unfolding process of the protein BBL,
      which has been previously characterized as a downhill folding protein. This test
      should be very useful for high-throughput design strategies and for the analysis
      of mutational effects in small proteins.

PMID- 15250681
TI  - Bridging the gap between in vitro and in vivo imaging: isostructural Re and 99mTc
      complexes for correlating fluorescence and radioimaging studies.
AB  - A bifunctional ligand that is capable of forming Re and 99mTc complexes as
      complementary fluorescent and radioactive probes was developed. The tridentate
      bis(quinoline) amine ligand, which is referred to as the SAACQ system, was
      prepared in a single step from Fmoc protected lysine in high yield. Reaction of
      the SAACQ ligand with [Re(CO)3Br3]2- resulted in the formation of the SAACQ
      (Re(CO)3)+complex which exhibits favorable fluorescence properties including a
      long lifetime and a large Stoke's shift. Because the SAACQ ligand is derived from
      an amino acid, it can readily be linked to or incorporated within peptides as a
      means of targeting the probe to specific receptors. To demonstrate this feature,
      the SAACQ ligand and the SAACQ-Re complex were incorporated into fMLFG, a peptide
      that binds to the formyl peptide receptor (FPR). Uptake of the fMLF[(SAACQ
      Re(CO)3)+]G conjugate into human leukocytes in vitro was visualized by
      fluorescence microscopy, and the observed distribution of the peptide was similar
      to that of a well-established fluorescent FPR probe. The corresponding Tc
      complex, fMLF[(SAACQ-99mTc(CO)3)+]G, was prepared in excellent yield from
      [99mTc(CO)3(OH2)3]+, which affords the opportunity to correlate the results of
      the microscopy experiments with in vivo radioimaging studies because the probes
      are isostructural.

PMID- 15250682
TI  - Tailor-made functionalization of silicon nitride surfaces.
AB  - This communication presents the first functionalization of a hydrogen-terminated
      silicon-rich silicon nitride (Si3Nx) surface with a well-defined, covalently
      attached organic monolayer. Properties of the resulting monolayers are monitored
      by measurement of the static water contact angle, X-ray photoelectron
      spectroscopy (XPS), and infrared reflection absorption spectroscopy (IRRAS).
      Further functionalization was performed by reaction of Si3Nx with a
      trifluoroethanol ester alkene (CH2=CH-(CH2)8CO2CH2CF3) followed by basic
      hydrolysis to afford the corresponding carboxylic acid-terminated monolayer with
      hydrophilic properties. These results show that Si3Nx can be functionalized with
      a tailor-made organic monolayer, has highly tunable wetting properties, and
      displays significant potential for further functionalization.

PMID- 15250683
TI  - Direct dynamics trajectory study of vibrational effects: can polanyi rules be
      generalized to a polyatomic system?
AB  - We present an ab initio direct dynamics trajectory study of the hydrogen
      abstraction reaction: H2CO+ + CD4 --> H2COD+ + CD3, with methane excited in two
      different distortion modes (nu4 and nu2). The trajectory simulations were able to
      reproduce experimental results and for the first time show how vibrational
      enhancement originates in reaction of small polyatomic species. Roughly equal
      contributions from two vibrational enhancement mechanisms were found. The
      "distortion" mechanism correlates the vibrational effects with vibration-induced
      reactant distortions, and the "velocity" mechanism correlates vibrational effects
      with vibrational velocities of the constituent atoms. This reaction has a
      reactant-like transition state and, thus, would correspond to an "early" barrier
      system in the context of the well-known Polanyi rules for predicting effects of
      vibration and collision energy. Straightforward application of these rules would
      predict that vibration should be ineffective in driving reaction, in disagreement
      with both experiment and trajectory results. Using the trajectories for guidance,
      we were able to construct a two-dimensional cut through the reaction potential
      energy surface that does suggest a predictive, Polanyi-type rule.

PMID- 15250684
TI  - Isolation, characterization of an intermediate in an oxygen atom-transfer
      reaction, and the determination of the bond dissociation energy.
AB  - The synthesis and structure of a phosphine oxide-bound intermediate molecule
      originating from a dioxo-molybdenum(VI) complex is described. The loss of
      phosphine oxide has been followed by surface-induced dissociation mass
      spectrometry that gave the bond dissociation energy of 29.5 (+/- 3.5) kcal/mol.
      Considering the bond dissociation energy for a Mo=O bond to be 100 kcal/mol, this
      value suggests that the primary driving force for the reaction is the formation
      of the intermediate complex.

PMID- 15250685
TI  - Synthesis of DNA triangles with vertexes of bis(terpyridine)iron(II) complexes.
AB  - The synthesis of the terpyridine derivative 1 tethered to a DNA oligonucleotide
      and its use for the preparation of two-way branched metal-organic modules capable
      of self-assembling into DNA triangles are described.

PMID- 15250686
TI  - A new type of square columnar liquid crystalline phases formed by facial
      amphiphilic triblock molecules.
AB  - A series of three novel liquid crystalline amphiphilic molecules is reported
      which are composed of three incompatible molecular parts, a rigid terphenyl core,
      two lipophilic decyloxy chains in the terminal 4- and 4' '-positions, and a polar
      group in the lateral 2'-position. The polar group comprises a polyether chain, an
      amide group, and a polyhydroxyalkyl end group (1-acylamino-1-deoxy-d-sorbitol
      derivatives). The self-organization of these compounds was studied by polarized
      light microscopy, differential scanning calorimetry, and different X-ray
      diffraction techniques. These investigations confirm a novel liquid crystalline
      phase with a square 2D-lattice (square columnar mesophase, plane group p4mm).
      This structure is built up by a set of three distinct columns, namely columns
      containing the polar lateral groups, columns incorporating the alkyl chains, and
      ribbons of the rodlike terphenyl units. The calamitic cores form walls bounding
      square-shaped channels occupied by the microsegregated polar lateral chains. The
      lipophilic columns containing alkyl chains are at the corners interconnecting the
      aromatic rods end-to-end.

PMID- 15250687
TI  - Refinement of the conformation of UDP-galactose bound to galactosyltransferase
      using the STD NMR intensity-restrained CORCEMA optimization.
AB  - The STD NMR technique has originally been described as a tool for screening large
      compound libraries to identify the lead compounds that are specific to target
      proteins of interest. The application of this technique in the qualitative
      epitope mapping of ligands weakly binding to proteins, virus capsid shells, and
      nucleic acids has also been described. Here we describe the application of the
      STD NMR intensity-restrained CORCEMA optimization (SICO) procedure for refining
      the bound conformation of UDP-galactose in galactosyltransferase complex using
      STD NMR intensities recorded at 500 MHz as the experimental constraints. A
      comparison of the SICO structure for the bound UDP-galactose in solution with
      that in the crystal structure for this complex shows some differences in ligand
      torsion angles and V253 side-chain orientation in the protein. This work
      describes the first application of an STD NMR intensity-restrained CORCEMA
      optimization procedure for refining the torsion angles of a bound ligand
      structure. This method is likely to be useful in structure-based drug design
      programs since most initial lead compounds generally exhibit weak affinity
      (millimolar to micromolar) to target proteins of pharmaceutical interest, and the
      bound conformation of these lead compounds in the protein binding pocket can be
      determined by the CORCEMA-ST refinement.

PMID- 15250688
TI  - Toward the development of ionically controlled nanoscopic molecular gates.
AB  - An ionically controlled nanoscopic molecular gate has been developed by using
      functionalized mesoporous materials. The system shows that control of mass
      transport at nanometric scale can be achieved by using suitable rigid solids and
      pH-active molecules. The design principle suggests new perspectives in the search
      of ionically tuned tailored materials and devices with a fine control of mass
      transport for new applications in fields such as drug delivery, selective removal
      of toxic species, sensing, or catalysis.

PMID- 15250689
TI  - X-ray crystal structure and EPR spectra of "arsenite-inhibited"
      Desulfovibriogigas aldehyde dehydrogenase: a member of the xanthine oxidase
      family.
AB  - X-ray crystallography has been used to determine the structure of arsenite
      inhibited aldehyde dehydrogenase from Desulfovibrio gigas, a member of the
      xanthine oxidase family of mononuclear molybdenum enzymes. The structure shows an
      AsO3 moiety bound to the molybdenum atom of the active site through one of the
      oxygen atoms. A reduced sample of arsenite-inhibited aldehyde dehydrogenase has a
      Mo(V) signal that shows anisotropic hyperfine and quadrupole coupling to one
      arsenic atom. This signal has a strong resemblance with a previously reported
      signal for arsenite-inhibited xanthine oxidase.

PMID- 15250690
TI  - Fabrication of magnetically separable mesostructured silica with an open pore
      system.
AB  - Magnetically separable mesostructured silica with an unobstructed pore system was
      fabricated through the deposition of cobalt nanoparticles on the outer surface of
      the submicron-sized silica particles. These cobalt nanoparticles were further
      protected by a nanometer-thick carbon shell against acid erosion. Due to the fact
      that the magnetic particles are grafted on the outer surface of the porous
      silica, the pores are still accessible for further modification, which could
      widen the application range of porous silica.

PMID- 15250691
TI  - Reaction of silyldihalomethyllithiums with nitriles: formation of alpha-keto
      acylsilanes via azirines and 1,3-rearrangement of silyl group from C to N.
AB  - A synthesis of alpha-keto acylsilanes, where 2-bromo-2H-azirine participates as a
      key intermediate, is reported. The reaction of silyldibromomethyllithium with
      aryl nitriles provides alpha-keto acylsilanes in good yields. Interestingly,
      silyldichloromethyllithium induces aza-1,3-Brook rearrangement of the silyl group
      in th reaction with nitriles. The rearrangement enables a three-component
      coupling reaction in a one-pot operation.

PMID- 15250692
TI  - Following the solvent directly during ultrafast excited state proton transfer.
AB  - Excited state intramolecular proton transfer in 1-chloroacetylaminoanthraquinone
      is investigated from the perspective of the solvent. Using a new two-dimensional
      nonlinear optical spectroscopy the solvent response is probed directly as the
      proton transfer takes place. The measurements indicate that solvent
      reorganization controls the proton transfer in acetonitrile by dynamically
      shifting the position of equilibrium in the excited state, even on subpicosecond
      time scales.

PMID- 15250693
TI  - Highly enantioselective separation using a supported liquid membrane
      encapsulating surfactant-enzyme complex.
AB  - We developed a highly enantioselective separation system for the optically active
      compounds, (S)-ibuprofen and l-phenylalanine, from their racemic mixtures by
      employing a supported liquid membrane (SLM) encapsulating a surfactant-lipase
      complex (or a surfactant-alpha-chymotrypsin complex). In the present system,
      enzymes encapsulated in the liquid-membrane phase effectively drove the
      enantioselective transport of optically active compounds through the SLM. This
      novel SLM allowed high enantioselectivity (ee over 91%) in the optical resolution
      of racemic ibuprofen and phenylalanine.

PMID- 15250694
TI  - Highly symmetric networks derived from cubane-related octametallic complexes of a
      new oxyanion of carbon, C4O7(4-), each molecule attached to eight neighbors by 24
      equivalent hydrogen bonds.
AB  - Aqueous reaction mixtures containing dihydroxyfumaric acid, M2+ (M = Zn, Co, Fe,
      and Mg) and acetate ion at room temperature give crystals, suitable for single
      crystal X-ray diffraction studies, of composition [(MII)8(C4O7)4(H2O)12].24H2O,
      in which the C4O74- component is the alkoxide-tricarboxylate tetra-anionic
      species -OC(CO2-)3, a new oxyanion of carbon. All four compounds crystallize in
      the body-centered space group I3m with cell dimensions a approximately 15.0 A.
      Discrete electrically neutral [(MII)8(C4O7)4(H2O)12] molecules are present, with
      a cubane-like core consisting of four trigonal prismatic metal centers and four
      mu3-alkoxo bridges from separate -OC(CO2-)3 ligands. The octametallic molecule is
      highly symmetrical, with four fac tri-aqua octahedral metal centers tetrahedrally
      appended to the central cubane-based [(MII)8(C4O7)4 ]8- unit. The molecules
      assemble in the crystal in a body-centered cubic fashion, each being attached to
      its eight neighbors by 24 equivalent hydrogen bonds-an extreme example of self
      complementarity.

PMID- 15250695
TI  - Putting a brake on an autonomous DNA nanomotor.
AB  - A strategy was developed to reversibly switch on/off an autonomous DNA nanomotor
      that contains a DNA enzyme. The multiple RNA cleavage of the DNAzyme powered the
      motor to move, and a strand displacement mechanism provided the basis for a
      reversible brake to the motor.

PMID- 15250696
TI  - Gallium cluster "magic melters".
AB  - Calorimetry measurements (using a method based on multicollision induced
      dissociation) have been performed for unsupported gallium clusters, Gan+ (n = 30
      50 and 55). Melting transitions have been identified from spikes in the heat
      capacities recorded as a function of temperature. There are enormous fluctuations
      in the melting temperatures and the heats of fusion with cluster size. Clusters
      with n = 31, 33, 37, and 45-47 are "magic melters" with particularly well-defined
      melting transitions. There is a strong correlation between the heats of fusion,
      entropies of fusion, and the stabilities of the clusters. However, these
      quantities are not strongly correlated with the melting temperatures.

PMID- 15250697
TI  - Bifunctional rhodium intercalator conjugates as mismatch-directing DNA alkylating
      agents.
AB  - A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky
      chrysenediimine ligand, and an aniline mustard has been prepared, and targeting
      of mismatches in DNA by this conjugate has been examined. The preferential
      alkylation of mismatched over fully matched DNA is found by a mobility shift
      assay at concentrations where untethered organic mustards show little reaction.
      The binding site of the Rh intercalator was determined by DNA photocleavage, and
      the position of covalent modification was established on the basis of the
      enhanced depurination associated with N-alkylation. The site-selective alkylation
      at mismatched DNA renders these conjugates useful tools for the covalent tagging
      of DNA base pair mismatches and new chemotherapeutic design.

PMID- 15250698
TI  - High-temperature electrocatalysis using thermophilic P450 CYP119: dehalogenation
      of CCl4 to CH4.
AB  - The use of a thermophilic cytochrome P450, CYP119, in electrocatalytic
      dehalogenations of C1 halocarbon solvents is studied. Temperature stable enzyme
      modified electrodes were constructed using sol-gel and polymeric surfactant
      approaches. CYP119 deposited in a dimethyldidodecylammonium poly(p-styrene
      sulfonate) (DDAPSS) film has good retention of electrochemical activity up to 80
      degrees C. At potentials approaching the FeII/I couple, the CYP119/DDAPSS films
      demonstrate high catalytic dehalogenations of the C1 chloromethanes CCl4, CHCl3,
      and CH2Cl2. Product analysis identified mixtures of sequentially dechlorinated
      products up to methane; no evidence for radical-coupled products was observed.
      The yield of methane from the CYP119-catalyzed reduction of CCl4 is increased 35
      fold from 25 degrees C to 55 degrees C. In combination with the lack of C2
      products, the facility of an overall eight-electron reductive dehalogenation
      suggests that the substrate is constrained within the protein during
      electrocatalytic turnover.

PMID- 15250700
TI  - Photochemistry of diketones: observation of a triplet state-oxygen adduct.
AB  - The presence of triplet state-oxygen adducts (a species previously proposed but
      never observed in a direct manner) is readily observed following laser flash
      photolysis studies of 2,2'-thenil. We report on the kinetic and spectroscopic
      parameters characteristic of this transient adduct.

PMID- 15250699
TI  - QM/MM determination of kinetic isotope effects for COMT-catalyzed methyl transfer
      does not support compression hypothesis.
AB  - Secondary alpha-D3 kinetic isotope effects calculated by the hybrid
      AM1/TIP3P/CHARMM method for the reaction of S-adenosylmethionine with catecholate
      anion in aqueous solution and catalyzed by rat liver catechol O-methyltransferase
      at 298 K are 0.94 and 0.85, respectively, in good accord with experiment. The
      large inverse effect for the enzymatic reaction is not due to compression but
      arises from significant increases in the stretching and bending force constants
      involving the isotopically substituted atoms of the transferring methyl group as
      between the reactant complex and the transition structure, larger than for the
      reaction in water.

PMID- 15250701
TI  - Rotaxanated conjugated sensory polymers.
AB  - Two highly emissive conjugated polymers with tethered rotaxane repeat units are
      reported. Hydrogen bonding between acidic alcohols and the N-heteroaromatic
      groups in the rotaxanes attenuates polymer fluorescence. In addition, the
      rotaxane groups create precise three-dimensional pockets for metal binding, which
      results in fluorescence quenching. Exposing thin films of Zn-doped polymers to
      alcohol vapors reverses the quenching by up to 25%.

PMID- 15250702
TI  - Covalent display of oligosaccharide arrays in microtiter plates.
AB  - A covalent array for the display of complex oligosaccharides in microtiter plates
      has been developed. This strategy is conducive to the display of carbohydrates to
      proteins of interest such as lectins and antibodies, including the broadly
      neutralizing antibody 2G12 against HIV envelope oligomannose and can be cleaved
      from the surface for further characterization by mass spectrometry. The system
      was used to probe the multivalent interaction of 2G12 with an optimal epitope (Kd
      0.1 muM).

PMID- 15250703
TI  - Regio- and diastereoselective rhodium-catalyzed allylic substitution with acyclic
      alpha-alkoxy-substituted copper(I) enolates: stereodivergent approach to 2,3,6
      trisubstituted dihydropyrans.
AB  - The regio- and diastereoselective transition metal-catalyzed allylic alkylation
      using alpha-heteroatom-substituted ketones and carboxylic acid derivatives
      represents a challenging and important synthetic transformation. We have
      developed a regio- and diastereoselective rhodium-catalyzed allylic alkylation
      reaction utilizing the copper(I) enolates derived from alkyl protected acyclic
      alpha-alkoxy aryl ketones. This study suggests that the ability to form a
      chelated enolate intermediate is crucial for obtaining high diastereoselectivity,
      whereas excellent regioselectivity is obtained regardless of the substituent.
      Hence, the excellent selectivity coupled with the synthetic utility of alpha
      alkoxy aryl ketone enolates makes this an important new method for the
      construction of acyclic adjacent ternary stereogenic centers. Finally, the
      synthetic utility of this protocol was highlighted through the conversion of the
      aryl ketone to the ester and the development of a stereodivergent approach to
      2,3,6-trisubstituted dihydropyrans relevant to target-directed synthesis.

PMID- 15250704
TI  - Assembly of an antiparallel homo-adenine DNA duplex by small-molecule binding.
AB  - Molecules that reversibly bind DNA and trigger the formation of non-Watson-Crick
      secondary structures would be useful in the design of dynamic DNA nanostructures
      and as potential leads for new therapeutic agents. We demonstrate that coralyne,
      a small crescent-shaped molecule, promotes the formation of a duplex secondary
      structure from homo-adenine oligonucleotides. AFM studies reveal that the
      staggered alignment of homo-adenine oligonucleotides upon coralyne binding
      produces polymers of micrometers in length, but only 2 nm in height. A DNA duplex
      was also studied that contained eight A.A mismatches between two flanking 7-bp
      Watson-Crick helices. CD spectra confirm that the multiple A.A mismatches of this
      duplex bind coralyne in manner similar to that of homo-adenine oligonucleotides.
      Furthermore, the melting temperature of this hybrid duplex increases by 13
      degrees C upon coralyne binding. These observations illustrate that the helical
      structure of the homo-adenine-coralyne duplex is compatible with the B-form DNA
      helix.

PMID- 15250705
TI  - Lithium-catalyzed hydroxide attack at the carbon atom of methyl phosphate.
AB  - The spontaneous hydrolysis of phosphate ester monoanions is relatively easy, but
      the reaction of water with simple phosphate ester dianion appears to be the
      slowest biomimetic reaction whose spontaneous rate has been measured in water,
      with an estimated half time of approximately 1012 years at room temperature in
      the absence of a catalyst. Here, we report an alternative mode of cleavage of
      methyl phosphate that involves hydroxide attack at the carbon atom of methyl
      phosphate and proceeds at a rate proportional to the square of the concentration
      of lithium hydroxide.

PMID- 15250706
TI  - Room temperature, high-yield synthesis of multiple shapes of gold nanoparticles
      in aqueous solution.
AB  - A seed-mediated growth method was used to control the morphology and dimensions
      of Au nanocrystals by the manipulation of the experimental parameters in aqueous
      solution at room temperature. This chemical route produces various structural
      architectures with rod-, rectangle-, hexagon-, cube-, triangle-, and starlike
      profiles and branched (such as bi-, tri-, tetra-, and multipod) Au nanocrystals
      of various dimensions in high yield in the presence of a single surfactant,
      cetyltrimethylammonium bromide.

PMID- 15250707
TI  - Ordered SBA-15 nanorod arrays inside a porous alumina membrane.
AB  - The growth of ordered nanorods of mesoporous SBA-15 inside a porous alumina
      membrane has been achieved for the first time by a simple sol-gel method. The
      obtained SBA-15 nanorods themselves have ordered hexagonal mesochannels with a
      size of about 6 nm and have been arranged to form hexagonal arrays by the
      limitation of pores of the alumina membrane. The synthesized alumina membrane
      with mesoporous SBA-15 inside combines the advantages of porous alumina membranes
      and mesoporous SBA-15 and provides fine and vertical mesochannels, which may
      serve as a new and efficient mold and lead to extensive applications in
      nanodevice fabrication, biomacromolecule separations, etc.

PMID- 15250708
TI  - Highly stereoselective prins cyclization of silylmethyl-substituted cyclopropyl
      carbinols to 2,4,6-trisubstituted tetrahydropyrans.
AB  - The homoallyl cation formed from a cyclopropyl carbinol that was vicinally
      substituted by a silylmethyl function underwent smooth Prins cyclization with
      aldehydes and ketones to form 2,4,6-trisubstituted tetrahydropyrans with very
      high stereoselectivity.

PMID- 15250709
TI  - Platinum- and gold-catalyzed cycloisomerization reactions of hydroxylated enynes.
AB  - Exposure of enynes containing a hydroxyl group at one of the propargylic
      positions to catalytic amounts of either PtCl2 or (PPh3)AuCl/AgSbF6 results in a
      selective rearrangement with formation of bicyclo[3.1.0]hexan-3-one derivatives.
      The same products are obtained by a "one-pot" process on treatment of an alkynal
      with allylchlorodimethylsilane (4) and PtCl2 via a reaction cascade involving an
      initial platinum-catalyzed allylation followed by the cycloisomerization of the
      homoallylic alcohol formed in situ. This novel skeletal reorganization process
      was implemented into a concise total synthesis of the terpenes sabinone (18) and
      sabinol (19). Furthermore it is shown that conversion of the hydroxylated enynes
      into the corresponding acetates followed by reaction with a cationic gold
      catalyst formed from (PPh3)AuCl and AgSbF6 opens entry into isomeric products
      bearing the ketone function at the C-2 position of the bicyclo[3.1.0]hexane
      skeleton. The outcome of a deuterium labeling experiment and the analysis of the
      stereochemical course of the cycloisomerization reaction are consistent with the
      formation of cyclopropylmethyl platinum carbene species as reactive
      intermediates.

PMID- 15250710
TI  - PtCl2-catalyzed cycloisomerizations of 5-en-1-yn-3-ol systems.
AB  - 5-En-1-yn-3-ol substrates bearing a free hydroxyl group or an acyl group are
      highly versatile partners for PtCl2-catalyzed cycloisomerizations. Electrophilic
      activation of the alkyne moiety triggers at wish a hydride or an O-acyl migration
      yielding at the end to regioisomeric keto derivatives. The efficient preparation
      of Sabina ketone, an important monoterpene precursor, has been worked out.

PMID- 15250711
TI  - Palladium-catalyzed reaction of 2-hydroxy-2-methylpropiophenone with aryl
      bromides: a unique multiple arylation via successive C-C and C-H bond cleavages.
AB  - 2-Hydroxy-2-methylpropiophenone undergoes a unique multiple arylation via C-C and
      C-H bond cleavages upon treatment with excess aryl bromides in the presence of a
      palladium catalyst to give 1,1,2,2-tetraarylethanes and 4,4-diaryl-1
      phenylisochroman-3-ones.

PMID- 15250712
TI  - Simple synthesis of an allenylidene heptavalent rhenium(d0) complex.
AB  - This paper reports a simple way to synthesize an allenylidene rhenium(VII)
      complex. The diimido adamantyl-thiolato allenylidene rhenium(VII) complex 2 was
      obtained through a metathetical reaction of phosphonioalkylidyne rhenium complex
      1 with diphenylketene and also structurally analyzed with X-ray diffraction.
      Complex 2 is the first d0 allenylidene complex with structure information.

PMID- 15250713
TI  - Polyborane reactions in ionic liquids: new efficient routes to functionalized
      decaborane and o-carborane clusters.
AB  - In contrast to reactions that have been observed in traditional organic solvents,
      decaborane olefin-hydroboration and alkyne-insertion reactions have been found to
      proceed in ionic liquid solvents without the need of a catalyst. These reactions
      now provide important new, high-yield synthetic pathways to functionalized
      decaborane and o-carborane clusters.

PMID- 15250714
TI  - Intramolecular cyclopropanation of unsaturated terminal epoxides.
AB  - Efficient lithium amide-induced intramolecular cyclopropanation of bishomoallylic
      and trishomoallylic epoxides is described. The methodology is used in an
      asymmetric synthesis of sabina ketone.

PMID- 15250715
TI  - Unidirectional current in a polyacetylene hetero-ionic junction.
AB  - Unidirectional electronic current is reported for a device based on the interface
      between an anionically functionalized and a cationically functionalized
      polyacetylene. The unidirectional current in this mixed ionically/electronically
      conducting system is electronic but is regulated by asymmetry in the ionic
      processes.

PMID- 15250716
TI  - Light-harvesting macroring accommodating a tetrapodal ligand based on
      complementary and cooperative coordinations.
AB  - A porphyrin macroring, mimicking the light-harvesting complex of photosynthetic
      purple bacteria, was synthesized by self-assembling trisporphyrinatoZn(II)
      complexes with imidazolyl substituents at both molecular terminals. Very strong
      complementary coordination of imidazolyl to Zn(II) afforded exclusively the
      cyclic trimer of trisporphyrin under dilute conditions at 27 degrees C in
      CHCl3/MeOH = 9/1 (v/v). 1H NMR spectra of the macroring indicate the existence of
      two topological isomers, one symmetric and one asymmetric. Use of three
      noncoordinated porphyrinatoZn(II) sites allows a tetrapodal ligand to be
      incorporated into the cavity of the macroring. A Job plot and the clear bending
      behavior on UV-vis titration indicated the formation a 1:1 complex; the
      heterogeneity of two topological isomers was not observed, and both isomers
      similarly accommodated the tetrapodal ligand. The association constant obtained
      by curve fitting analysis was 8 x 108 M-1 in toluene. This large association
      constant reflects the cooperative nature of three coordination sites.

PMID- 15250717
TI  - Synthesis, reactivity, and ligand properties of a stable alkyl carbene.
AB  - Stable tert-butyl diisopropylamino carbene is more nucleophilic but also more
      electrophilic than diamino carbenes; it undergoes cyclopropanation reactions and
      easily binds to metal fragments.

PMID- 15250718
TI  - Direct evidence for ferromagnetism of nanometer-scale palladium by contact with
      perovskite manganite.
AB  - Using a template method, we have synthesized hybrid Pd/La0.7Ca0.3-xSrxMnO3
      (LCSMO) materials, which were evidenced by SEM, TEM, X-ray powder diffraction,
      and magnetization measurements. It was found that the Pd moment was induced by
      the rough LCSMO oxide, which was quantitatively analyzed. Our results provided
      direct evidence for ferromagnetism of nanosized Pd materials by contact with the
      perovskite manganite.

PMID- 15250719
TI  - Significant pKa perturbation of nucleobases is an intrinsic property of the
      sequence context in DNA and RNA.
AB  - The pH titration and NMR studies (pH 6.6-12.5) in the heptameric isosequential
      ssDNA and ssRNA molecules, [d/r(5'-CAQ1GQ2AC-3', with variable Q1/Q2)], show that
      the pKa of the central G residue within the heptameric ssDNAs (DeltapKa = 0.67 +/
      0.03) and ssRNAs (DeltapKa = 0.49 +/- 0.02) is sequence-dependent. This variable
      pKa of the G clearly shows that its pseudoaromatic character, hence, its chemical
      reactivity, is strongly modulated and tuned by its sequence context. In
      contradistinction to the ssDNAs, the electrostatic transmission of the pKa of the
      G moiety to the neighboring A or C residues in the heptameric ssRNAs (as observed
      by the response of the aromatic marker protons of As or Cs) is found to be
      uniquely dependent upon the sequence composition. This demonstrates that the
      neighboring As or Cs in ssRNAs have variable electrostatic efficiency to interact
      with the central G/G-, which is owing to the variable pseudoaromatic characters
      (giving variable chemical reactivities) of the flanking As or Cs compared to
      those of the isosequential ssDNAs. The sequence-dependent variation of pKa of the
      central G and the modulation of its pKa transmission through the nearest
      neighbors by variable electrostatic interaction is owing to the electronically
      coupled nature of the constituent nucleobases across the single strand, which
      demonstrates the unique chemical basis of the sequence context specificity of DNA
      or RNA in dictating the biological interaction, recognition, and function with
      any specific ligand.

PMID- 15250720
TI  - Biliverdin reduction by cyanobacterial phycocyanobilin:ferredoxin oxidoreductase
      (PcyA) proceeds via linear tetrapyrrole radical intermediates.
AB  - Cyanobacterial phycocyanobilin:ferredoxin oxidoreductase (PcyA) catalyzes the
      four electron reduction of biliverdin IXalpha (BV) to phycocyanobilin, a key step
      in the biosynthesis of the linear tetrapyrrole (bilin) prosthetic groups of
      cyanobacterial phytochromes and the light-harvesting phycobiliproteins. Using an
      anaerobic assay protocol, optically detected bilin-protein intermediates,
      produced during the PcyA catalytic cycle, were shown to correlate well with the
      appearance and decay of an isotropic g approximately 2 EPR signal measured at low
      temperature. Absorption spectral simulations of biliverdin XIIIalpha reduction
      support a mechanism involving direct electron transfers from ferredoxin to
      protonated bilin:PcyA complexes.

PMID- 15250721
TI  - Complexed nitrogen heterosuperbenzene: the coordinating properties of a
      remarkable ligand.
AB  - Tetra-peri-(tert-butyl-benzo)-di-peri-(pyrimidino)-coronene 1, the parent
      compound of the nitrogen heterosuperbenzene family N-HSB, is employed as a novel
      monotopic ligand in the formation of [Pd(eta3-C3H5)(1)]PF6 2 and
      [Ru(bpy)2(1)](PF6)2 (where bpy = 2,2'-bipyridine 3a and d8-2,2'-bipyridine 3b).
      These N-coordinated complexes are fully characterized by 1H NMR and IR
      spectroscopy and ESI-MS. Metal coordination has a profound effect on both the
      absorption and the emission properties of 1. Pd(II) coordination causes a red
      shift in the low-energy absorptions, a decrease in the intensity of the n-pi
      absorptions, and a quenching of the emission. Ru(II) coordination causes
      absorption throughout the visible region and creates two new complexes that join
      an elite group of compounds known as "black" absorbers. 3a and 3b possess two
      discernible 1MLCT bands. The one of exceptionally low energy (lambda(max) = 615
      nm) has an associated (3)MLCT emission (lambda(max) = 880 nm) due to the
      unprecedented electron delocalization and acceptor properties of the rigid
      aromatic N-HSB 1. Both Ru(II) complexes are near-IR emitters with unusually
      protracted emission lifetimes of 320 ns at 77 K. They are photochemically inert,
      and their electrochemical properties are consistent with the presence of a low
      lying pi orbital on 1. The first two reversible reductions (E(1/2) (CH3CN), -0.54
      V, -1.01 V vs SCE) are due to the stepwise reduction of 1 and are anodically
      shifted as compared to [Ru(bpy)3]2+. Temperature- and concentration-dependent NMR
      studies on 2 and 3a suggest extensive aggregation is occurring in solution.

PMID- 15250722
TI  - The dynamic character of the G-quadruplex element in the c-MYC promoter and
      modification by TMPyP4.
AB  - The nuclease hypersensitivity element III1 (NHE III1) upstream of the P1 and P2
      promoters of c-MYC controls 80-90% of the transcriptional activity of this gene.
      The purine-rich strand in this region can form a G-quadruplex structure that is a
      critical part of the silencer element for this promoter. We have demonstrated
      that this G-quadruplex structure can form a mixture of four biologically relevant
      parallel-loop isomers, which upon interaction with the cationic porphyrin TMPyP4
      are converted to mixed parallel/antiparallel G-quadruplex structures.

PMID- 15250724
TI  - Basicity of nucleophilic carbenes in aqueous and nonaqueous solvents-theoretical
      predictions.
AB  - The complete basis set method CBS-QB3 was used in conjunction with the CPCM
      solvation model to predict both the absolute and relative pKa's of 12
      nucleophilic carbenes in dimethyl sulfoxide (DMSO), acetonitrile (MeCN), and
      water. Average absolute pKa values in DMSO ranged from 14.4 +/- 0.16 for 3
      methylthiazol-2-ylidene (12) to 27.9 +/- 0.23 in the case of
      bis(dimethylamino)carbene (11), while values in MeCN were determined to be
      between 25.7 +/- 0.16 (12) and 39.1 +/- 0.25 (11). Relative pKa calculations
      yielded similar results. Calculations in aqueous solution gave pKa's between 21.2
      +/- 0.2 (12) and 34.0 +/- 0.3 (11). Excellent agreement between calculated and
      experimental pKa's was obtained for the few cases where experimental numbers are
      available, confirming that this theoretical approach may be used to calculate
      highly accurate pKa values.

PMID- 15250723
TI  - Propeller-type parallel-stranded G-quadruplexes in the human c-myc promoter.
AB  - The nuclease-hypersensitivity element III1 in the c-myc promoter is a good
      anticancer target since it largely controls transcriptional activation of the
      important c-myc oncogene. Recently, the guanine-rich strand of this element has
      been shown to form an equilibrium between G-quadruplex structures built from two
      different sets of G-stretches; two models of intramolecular fold-back
      antiparallel-stranded G-quadruplexes, called "basket" and "chair" forms, were
      proposed. Here, we show by NMR that two sequences containing these two sets of G
      stretches form intramolecular propeller-type parallel-stranded G-quadruplexes in
      K(+)-containing solution. The two structures involve a core of three stacked G
      tetrads formed by four parallel G-stretches with all anti guanines and three
      double-chain-reversal loops bridging three G-tetrad layers. The central loop
      contains two or six residues, while the two other loops contain only one residue.

PMID- 15250725
TI  - Creation of hoop- and bowl-shaped benzenoid systems by selective detraction of
      [60]fullerene conjugation. [10]cyclophenacene and fused corannulene derivatives.
AB  - Selective penta-addition of a methylcopper reagent followed by addition of a
      phenylcopper reagent to a suitably modified synthetic intermediate results in
      creation of 40pi-electron systems-hoop- and bowl-shaped cyclic benzenoid
      compounds, [10]cyclophenacene, and dibenzo-fused corannulene derivatives. The
      40pi-electron cyclophenacene derivatives have been found to be chemically stable,
      yellow-colored, luminescent (560 nm), and EPR-silent. X-ray crystallographic
      analysis provided precision structural data sets. The dibenzo-fused corannulene
      derivatives exhibit blue-green (460 nm) to red (649 nm) fluorescence.

PMID- 15250726
TI  - Characterization, supramolecular assembly, and nanostructures of thiophene
      dendrimers.
AB  - We report the synthesis and characterization of dendritic thiophene derivatives
      with their unique supramolecular assembly into 2-D crystals, nanowires, and
      nanoparticle aggregates. The structure and size of the dendrons and dendrimers
      have been confirmed with various techniques, such as NMR, SEC, and MALDI-TOF-MS.
      The mass values were consistent with the mass observed by MALDI-TOF-MS, whereas
      SEC measurements also gave useful information on the hydrodynamic volume of the
      individual dendrimers. The interesting electrooptical properties were highlighted
      by very broad absorption spectra and narrower fluorescence consistent with their
      electrochemical behavior. The self-organization of the dendrimers on the solid
      substrate is dependent on the nature of the substrate, preparation methods, and
      the molecule-molecule and molecule-substrate interactions. Thus, 14T-1 and 30T
      both formed globular aggregates on mica surface, while 14T-1 also formed
      nanowires on graphite surface. On the other hand, the larger 30T was observed to
      form 2-D crystalline structures. By varying the alkyl chain length attached to
      14T-1, we were also able to obtain 2-D crystals on graphite. This showed that the
      different symmetry of packing for 30T and 14T-1 is also dependent on several
      factors, such as the molecular shape, size, and the presence of noncovalent
      intermolecular interactions. The results demonstrated the unique ability of
      thiophene dendrimers to form nanostructures on surfaces.

PMID- 15250727
TI  - Palladium(0)-catalyzed synthesis of medium-sized heterocycles by using
      bromoallenes as an allyl dication equivalent.
AB  - We have developed a highly regio- and stereoselective synthesis of medium-sized
      heterocycles containing one or two heteroatoms via cyclization of bromoallenes
      bearing an oxygen, nitrogen, or carbon nucleophilic functionality in the presence
      of a palladium(0) catalyst and alcohol. In this reaction, bromoallenes act as an
      allyl dication equivalent, and the intramolecular nucleophilic attack takes place
      exclusively at the central carbon atom of the allene moiety. Interestingly,
      bromoallenes having a carbon nucleophile with a five-atom tether afford eight
      membered rings with trans-configuration, while those having an oxygen or a
      nitrogen nucleophile give the corresponding cis-rings selectively. This is the
      first example that demonstrates the synthesis of medium-sized rings via
      cyclization of bromoallenes, and this reaction provides a very useful method for
      a catalytic synthesis of seven- and eight-membered heterocycles without using
      high dilution conditions.

PMID- 15250728
TI  - Development of a catalytic electron transfer system mediated by transition metal
      ate complexes: applicability and tunability of electron-releasing potential for
      organic transformations.
AB  - We have developed a catalytic electron transfer (ET) system composed of a
      transition metal ate complex (Me3M(II)Li; M = Co(II), Mn(II), Fe(II)) and
      magnesium. This system (catalytic Me3M(II)Li/Mg) turned out to be effective for
      various ET reactions, such as the desulfonylation of N-phenylsulfonyl amides, and
      others (the chemoselective cleavage of O-allyl groups, the reduction of nitro
      groups, the partial reduction of diketones, and the reductive coupling of
      diphenyliodonium salt). The ET ability of this system can be tuned by changing
      the ligands of the ate complexes. This tunability was experimentally and
      electrochemically demonstrated: alkoxy-ligated and dianion-type ET ate complexes
      showed attenuated and enhanced reducing abilities, respectively. The modification
      of the ET abilities was evaluated by means of electrochemical measurements and
      chemical reactions. These results provide a basis for the design of various
      tailor-made ET ate complexes.

PMID- 15250729
TI  - Photoisomerization and photodissociation of aniline and 4-methylpyridine.
AB  - Photoisomerization and photodissociation of aniline and 4-methylpyridine at 193
      nm were studied separately using multimass ion imaging techniques. Photofragment
      translational energy distributions and dissociation rates were measured. Our
      results demonstrate that more than 23% of the ground electronic state aniline and
      10% of 4-methylpyridine produced from the excitation by 193 nm photons after
      internal conversion isomerize to seven-membered ring isomers, followed by the H
      atom migration in the seven-membered ring, and then rearomatize to both
      methylpyridine and aniline prior to dissociation. The significance of this
      isomerization is that the carbon, nitrogen, and hydrogen atoms belonging to the
      alkyl or amino groups are involved in the exchange with those atoms in the
      aromatic ring during the isomerization.

PMID- 15250730
TI  - Sequential arrangement of gamma-valerolactone enantiomers enclathrated in cholic
      acid channels as studied by 13C solid-state NMR: elucidation of the optical
      resolution mechanism.
AB  - The mechanism of the optical resolution of gamma-valerolactone (VAL) enantiomers
      by enclathration in cholic acid (CA) channels was investigated. 13C cross
      polarization magic-angle spinning spectra of CA/VAL inclusion compounds show four
      methyl 13C peaks of VAL with different intensities depending on the enantiomeric
      ratios. The four peaks were assigned to the inner and end (S)-(-)-enantiomers (S)
      in the S domain and the inner and end (R)-(+)-enantiomers (R). The relative
      intensities of the four methyl 13C peaks cannot be explained by the random
      process model for inclusion but are successfully reproduced by assuming the first
      order Markov process, in which the inclusion probabilities of S and R depend on
      which enantiomer has precedingly entered the CA channel. The probability p(S/S)
      that two S enantiomers successively enter a channel is thus found to be 83%, and
      p(R/R) is 50%. The large probability of p(S/S) indicates that once an S
      enantiomer enters a channel, it become easy for other S enantiomers to
      successively enter the channel, and thus the large enantiomeric excess of S is
      obtained. The inclusion probabilities of S and R were confirmed by 1D 13C-13C
      polarization-transfer experiments among the four methyl carbons of VAL in the CA
      channel. Further, we found that the 13C line widths and peak positions of the CA
      tail group change depending on the enantiomeric ratio. We concluded that once S
      is included, it changes the conformation of the CA tail group so that other S
      enantiomers become easy to successively enter the channel.

PMID- 15250731
TI  - Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a
      Et2Zn/linked-BINOL complex: synthesis of either anti- or syn-beta-amino alcohols.
AB  - Full details of a direct catalytic asymmetric Mannich-type reaction of a
      hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing
      the proper protective groups on imine nitrogen, either anti- or syn-beta-amino
      alcohol was obtained in good diastereomeric ratio, yield, and excellent
      enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp)
      imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99%
      yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in
      anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst
      turnover number (TON) is also noteworthy. Catalyst loading was successfully
      reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05
      mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked
      BINOL complex exhibited far better TON than in previous reports of catalytic
      asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for
      the high catalyst efficiency as well as transformations of Mannich adducts are
      also described.

PMID- 15250732
TI  - Me2AlCH2PMe2: a new, bifunctional cocatalyst for the Ni(II)-catalyzed
      oligomerization of PhSiH3.
AB  - The role of methylaluminoxane (MAO) in the Ni-catalyzed dehydrogenative
      homologation of PhSiH3 has been investigated with a view to designing new
      cocatalysts possessing well-defined chemical compositions and structures. These
      studies show that species such as the bifunctional reagent (Me2PCH2AlMe2)2, 3,
      should act as co-catalyst for the Si-Si bond formation reactions. Thus, it was
      found that the combination of (1-Me-indenyl)Ni(PPh3)Me, 2a, and 3 (Ni/Al ratio of
      1:1) converts PhSiH3 to cyclic oligomers (PhSiH)n with a turnover frequency (TOF)
      of >500 h(-1), 50 times faster than with 2a alone. Detailed NMR studies have
      indicated that this acceleration is due to the formation of the intermediate (1
      Me-indenyl)Ni(Me)(Me2PCH2AlMe2), 4. Coordination of the PMe2 moiety in this
      complex to the Ni center allows the tethered AlMe2 moiety to interact with the Ni
      Me moiety in such a way that promotes fairly slow Al-Me/Ni-CD3 exchange (t(1/2)
      ca. 12 h) but accelerates the Si-H bond activation and Si-Si bond formation
      reactions. The catalysis promoted by 2a/3 proceeds even faster in the presence of
      NEt3 or THF (TOF > 1600 h(-1)), because these Lewis bases favor the monomeric
      form of 3, which in turn favors the formation of 4. On the other hand, the much
      more nucleophilic base quinuclidine suppresses the catalysis (TOF < 300 h(-1)) by
      hindering the Ni.R.Al interactions. These observations point to an emerging
      strategy for using bifunctional reagents such as 3 to place geometrically
      constrained Lewis acid moieties adjacent to metal centers, thereby activating
      certain metal-ligand bonds.

PMID- 15250733
TI  - Double geminal C-H activation and reversible alpha-elimination in 2-aminopyridine
      iridium(III) complexes: the role of hydrides and solvent in flattening the free
      energy surface.
AB  - [H2Ir(OCMe2)2L2]BF4 (1) (L = PPh3), a preferred catalyst for tritiation of
      pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe2;
      py = 2-pyridyl) to give chelate carbene [H2Ir(py-N(Me)CH=)L2]BF4 (2a) via
      cyclometalation, H2 loss, and reversible alpha-elimination. Agostic intermediate
      [H2Ir(py-N(Me)CH2-H)L2]BF4) (4a), seen by NMR, is predicted (DFT(B3PW91)
      computations) to give C-H oxidative addition to form the alkyl intermediate
      [(H)(eta2-H2)Ir(py-N(Me)CH2-)L2]BF4. Loss of H2 leads to the fully characterized
      alkyl [HIr(OCMe2)(py-N(Me)CH2-)L2]BF4 (3a(Me2CO)), which loses acetone to give
      alkylidene hydride 2a by rapid reversible alpha-elimination. 2a rapidly reacts
      with excess H2 in d6-acetone to generate [H2Ir(OC(CD3)2)2L2]BF4 (1-d12),
      3a((CD3)2CO), and py-NMe2 in a 1:1:1 ratio, showing reversibility and accounting
      for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH2)4
      gives the fully characterized carbene 2c. A cis-L(2) carbene intermediate, cis
      2c, observed by NMR, reacts with CO via retro alpha-elimination to give the alkyl
      3cCO, while the trans isomer, 2c, does not react; retro alpha-elimination thus
      requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with
      experiment, computational studies show a particularly flat PE surface with
      activation of the agostic C-H bond giving a less stable H2 complex, then
      formation of a kinetic carbene complex with cis-L, only seen experimentally for
      py-N(CH2)4. Hydrides at key positions, together with gain or loss of solvent and
      H2, flatten the PE (DeltaG) surfaces to allow fast catalysis.

PMID- 15250734
TI  - Single-molecule magnets of ferrous cubes: structurally controlled magnetic
      anisotropy.
AB  - Tetranuclear Fe(II) cubic complexes were synthesized with Schiff base ligands
      bridging the Fe(II) centers. X-ray structural analyses of six ferrous cubes,
      [Fe4(sap)4(MeOH)4].2H2O (1), [Fe4(5-Br-sap)4(MeOH)4] (2), [Fe4(3-MeO
      sap)4(MeOH)4].2MeOH (3), [Fe4(sae)4(MeOH)4] (4), [Fe4(5-Br-sae)4(MeOH)4].MeOH
      (5), and [Fe4(3,5-Cl2-sae)4(MeOH)4] (6) (R-sap and R-sae were prepared by
      condensation of salicylaldehyde derivatives with aminopropyl alcohol and
      aminoethyl alcohol, respectively) were performed, and their magnetic properties
      were studied. In 1-6, the alkoxo groups of the Schiff base ligands bridge four
      Fe(II) ions in a mu3-mode forming [Fe4O4] cubic cores. The Fe(II) ions in the
      cubes have tetragonally elongated octahedral coordination geometries, and the
      equatorial coordination bond lengths in 4-6 are shorter than those in 1-3. Dc
      magnetic susceptibility measurements for 1-6 revealed that intramolecular
      ferromagnetic interactions are operative to lead an S = 8 spin ground state.
      Analyses of the magnetization data at 1.8 K gave the axial zero-field splitting
      parameters (D) of +0.81, +0.80, +1.15, -0.64, -0.66, and -0.67 cm(-1) for 1-6,
      respectively. Ac magnetic susceptibility measurements for 4-6 showed both
      frequency dependent in- and out-of-phase signals, while 1-3 did not show out-of
      phase signals down to 1.8 K, meaning 4-6 are single-molecule magnets (SMMs). The
      energy barriers to flip the spin between up- and down-spin were estimated to
      28.4, 30.5, and 26.2 K, respectively, for 4-6. The bridging ligands R-sap2- in 1
      3 and R-sae2- in 4-6 form six- and five-membered chelate rings, respectively,
      which cause different steric strain and Jahn-Teller distortions at Fe(II)
      centers. The sign of the D value was discussed by using angular overlap model
      (AOM) calculations for irons with different coordination geometry.

PMID- 15250735
TI  - Synthesis and properties of compressed dihydride complexes of iridium:
      theoretical and spectroscopic investigations.
AB  - Reaction of [Cp*Ir(P-P)Cl][B(C6F5)4] (P-P = bisdimethydiphosphinomethane (dmpm),
      bisdiphenyldiphosphinomethane (dppm)) with [Et3Si][B(C6F5)4] in methylene
      chloride under 1 atm of hydrogen gas affords the dicationic compressed dihydride
      complexes [Cp*Ir(P-P)H2][B(C6F5)4]2. These dicationic complexes are highly acidic
      and are very readily deprotonated to the corresponding monohydride cations. When
      the preparative reaction is carried out under HD gas, the hydride resonance
      exhibits JHD = 7-9 Hz, depending upon the temperature of observation, with higher
      values of JHD observed at higher temperatures. A thermally labile rhodium
      analogue, [CpRh(dmpm)(H2)][B(C6F5)4]2, was prepared similarly. A sample prepared
      with HD gas gave JHD = 31 Hz and J(HRh) = 31 Hz, allowing the Rh complex to be
      identified as a dihydrogen complex. Quantum dynamics calculations on a density
      functional theory (DFT) potential energy surface have been used to explore the
      structure of the Ir complexes, with particular emphasis on the nature of the
      potential energy surface governing the interaction between the two hydride
      ligands and the Ir center.

PMID- 15250736
TI  - A fast photoswitch for minimally perturbed peptides: investigation of the trans-
      >cis photoisomerization of N-methylthioacetamide.
AB  - Thio amino acids can be integrated into the backbone of peptides without
      significantly perturbing their structure. In this contribution we use ultrafast
      infrared and visible spectroscopy as well as state-of-the-art ab initio
      computations to investigate the photoisomerization of the trans form of N
      methylthioacetamide (NMTAA) as a model conformational photoswitch. Following the
      S2 excitation of trans-NMTAA in water, the return of the molecule into the trans
      ground state and the formation of the cis isomer is observed on a dual time
      scale, with a fast component of 8-9 ps and a slow time constant of approximately
      250 ps. On both time scales the probability of isomerization to the cis form is
      found to be 30-40%, independently of excitation wavelength. Ab initio
      CASPT2//CASSCF photochemical reaction path calculations indicate that, in vacuo,
      the trans-->cis isomerization event takes place on the S1 and/or T1 triplet
      potential energy surfaces and is controlled by very small energy barriers, in
      agreement with the experimentally observed picosecond time scale. Furthermore,
      the calculations identify one S2/S1 and four nearly isoenergetic S1/S0 conical
      intersection decay channels. In line with the observed isomerization probability,
      only one of the S1/S0 conical intersections yields the cis conformation upon S1-
      >S0 decay. A substantially equivalent excited-state relaxation results from four
      T1/S0 intersystem crossing points.

PMID- 15250737
TI  - Direct electrochemiluminescence detection of oxidized DNA in ultrathin films
      containing [Os(bpy)2(PVP)10]2+.
AB  - Direct electrochemiluminescence (ECL) involving oxidized DNA was demonstrated in
      ultrathin films of cationic polymer [Os(bpy)2(PVP)10]2+ [PVP = poly(vinyl
      pyridine)] assembled layer-by-layer with DNA or oligonucleotides.
      Electrochemically oxidized Os(II) sites generated ECL from films containing oxo
      guanines on DNA formed by chemical oxidation using Fenton reagent. Films
      combining DNA, [Ru(bpy)2(PVP)10]2+, and [Os(bpy)2(PVP)10]2+ had Os(II) sites that
      produced ECL specific for oxidized DNA, and Ru(II) sites gave ECL from reaction
      with oxo-adenines, chemically damaged DNA, and possibly from cleaved DNA strands.

PMID- 15250738
TI  - Nature of the peroxo intermediate of the W48F/D84E ribonucleotide reductase
      variant: implications for O2 activation by binuclear non-heme iron enzymes.
AB  - Analysis of the spectroscopic signatures of the R2-W48F/D84E biferric peroxo
      intermediate identifies a cis mu-1,2 peroxo coordination geometry. DFT geometry
      optimizations on both R2-W48F/D84E and R2-wild-type peroxo intermediate models
      including constraints imposed by the protein also identify the cis mu-1,2 peroxo
      geometry as the most stable peroxo intermediate structure. This study provides
      significant insight into the electronic structure and reactivity of the R2
      W48F/D84E peroxo intermediate, structurally related cis mu-1,2 peroxo model
      complexes, and other enzymatic biferric peroxo intermediates.

PMID- 15250740
TI  - Reactions of orthophthalaldehyde with nucleophiles.

PMID- 15250742
TI  - Organic photorefractives: mechanisms, materials, and applications.

PMID- 15250741
TI  - Application of amperometric biosensors to the determination of vitamins and alpha
      amino acids.

PMID- 15250743
TI  - Preparations of C-nitroso compounds.

PMID- 15250744
TI  - Asymmetric synthesis of isoquinoline alkaloids.

PMID- 15250745
TI  - Samarium(II)-iodide-mediated cyclizations in natural product synthesis.

PMID- 15250746
TI  - Standard partial molar volumes of electrolytes and ions in nonaqueous solvents.

PMID- 15250747
TI  - Enantioselective palladium-catalyzed transformations.

PMID- 15250748
TI  - The measurement of contingent valuation for health economics.
AB  - In health economics, contingent valuation is a method that elicits an
      individual's monetary valuations of health programmes or health states. This
      article reviews the theory and conduct of contingent valuation studies, with
      suggestions for improving the future measurement of contingent valuation for
      health economics applications. Contingent valuation questions can be targeted to
      any of the following groups: the general population, to value health insurance
      premiums for programmes; users of a health programme, to value the associated
      programme costs; or individuals with a disease, to evaluate health states. The
      questions can be framed to ask individuals how much they would pay to obtain
      positive changes in health status or avoid negative changes in health status
      ('willingness to pay'; WTP) or how much they would need to be paid to compensate
      for a decrease in health status or for foregoing an improvement in heath status
      ('willingness to accept'; WTA). In general WTP questions yield more accurate and
      precise valuations than WTA questions. Payment card techniques, with follow-up
      bidding using direct interviews with visual aids, are well suited for small
      contingent valuation studies. Several biases may be operative when assessing
      contingent valuation, including biases in the way participants are selected, the
      way in which the questions are posed, the way in which individuals interpret
      probabilities and value gains relative to losses, and the way in which missing or
      extreme responses are interpreted. An important aspect of all contingent
      valuation studies is an assessment of respondents' understanding of the
      evaluation method and the valuation task. Contingent valuation studies should
      measure the potential influence of biases, the validity of contingent valuation
      tests as measures of QOL, and the reliability and responsiveness of responses.
      Future research should address equity concerns associated with using contingent
      valuation and explore contingent valuation as a measure of utility for health
      states, particularly those that are minor or temporary.

PMID- 15250749
TI  - Effect of second-generation antipsychotics on employment and productivity in
      individuals with schizophrenia: an economic perspective.
AB  - Schizophrenia is a serious mental illness that imposes a considerable burden not
      only on those who are ill, but also on their families, neighbours and the wider
      society. Costs associated with treating people with schizophrenia are those
      derived from the use of a wide range of services provided by public psychiatric
      facilities and/or by voluntary and private agencies. In addition, a large part of
      the economic impact of schizophrenia is related to the difficulties that patients
      encounter in finding and keeping paid employment. The introduction of second
      generation antipsychotics (SGAs), also defined as atypicals, has increased the
      therapeutic options available for individuals with schizophrenia. Potential
      benefits of these agents include a more favourable profile in terms of positive
      and negative symptoms, less adverse effects and better cognitive functioning than
      first-generation antipsychotics (FGAs). As a consequence, SGAs might favourably
      affect the capacity, seriously impaired in schizophrenia, of finding and keeping
      paid employment. To date, only 13 published studies have investigated the effect
      of SGA agents on employment and work productivity. Clozapine was studied in eight
      studies, while both olanzapine and risperidone were studied in three. Clozapine
      emerged as the SGA with at least some effect on work status. However, all but one
      clozapine study enrolled only a few individuals and did not adopt an experimental
      design, making it very difficult to judge the validity and generalisability of
      findings. Taken together, studies found little benefit, in terms of employment
      and work productivity, for the use of SGAs compared with FGAs. The evidence
      available suggests that until data demonstrate a robust effect of newer agents on
      employment, it remains mandatory for mental health professionals to use the most
      effective drug treatment together with non-pharmacological interventions, such as
      vocational rehabilitative programmes nested into models of community psychiatric
      care, which have proven effect on the capacity of finding and keeping paid
      employment. This will ensure that the economic impact of schizophrenia is most
      effectively contained.

PMID- 15250750
TI  - Economic aspects of pneumococcal pneumonia: a review of the literature.
AB  - In this review, the economic aspects of pneumococcal pneumonia are analysed,
      including the costs, cost effectiveness and cost benefit of treatment and
      prevention. We identified eight cost-of-illness studies, 15 analyses comparing
      the costs of different treatment options and 15 economic evaluations of
      prevention that met our search criteria. The studies were conducted largely in
      Europe and the US. Most pertained to community-acquired pneumonia (CAP) in
      general, without specific analysis of pneumococcus-related illness. Many of the
      studies were considered to be of poor quality for the following reasons:
      comparison without randomisation or control variables, disregard of health
      outcomes, small sample size, restriction of costs to drug costs and vague or
      disputable sources of cost information. In the US, hospitalisation costs
      resulting from CAP can be estimated to be between US 7,000 dollars and US 8,000
      dollars per admission or US 4 million dollars per 100,000 population.
      Hospitalisation costs are significant (representing about 90% of total costs),
      but are much lower in Europe than in the US (one-third to one-ninth of the US
      estimates in the UK and Spain, respectively). In general, economic studies of
      treatment for pneumococcal pneumonia are in line with clinical evidence. A drug
      with proven clinical effectiveness would also appear to be supported from an
      economic stand point. Furthermore, economic data support an early switch from an
      intravenous to an oral antibacterial, the use of quinolones for inpatients with
      CAP, and also the use of guidelines built on clinical evidence. Of all the
      possible preventive strategies for pneumococcal pneumonia, only vaccination has
      been subjected to economic evaluation. Pneumococcal polysaccharide vaccine seems
      relatively cost effective (and potentially cost saving) for those between 65 and
      75 years of age, for military recruits and for HIV positive patients with a
      sufficiently high CD4 cell count. Evaluations of the pneumococcal conjugate
      vaccine (PCV) indicate the price of the vaccine to be the main determinant of
      cost effectiveness. As the current price is high (in the order of US 50 dollars
      per dose), the economic attractiveness of the universal PCV vaccination
      strategies hinges on the potential for price reductions and the willingness of
      decision makers to adopt a societal perspective.

PMID- 15250751
TI  - Healthcare costs with tiotropium plus usual care versus usual care alone
      following 1 year of treatment in patients with chronic obstructive pulmonary
      disorder (COPD).
AB  - BACKGROUND: Healthcare costs for chronic obstructive pulmonary disease (COPD)
      have continued to increase with the increasing prevalence of the disease. New
      interventions that can reduce the medical costs of COPD are needed. Tiotropium
      bromide, a once-daily inhaled anticholinergic, has been evaluated in patients
      with COPD enrolled in two 1-year randomised, double-blind, placebo-controlled
      (usual care) trials which showed the drug reduced exacerbations and improved
      spirometry, dyspnoea, and health status. OBJECTIVE: To retrospectively assess the
      direct costs of medical care for COPD in a US healthcare setting for patients
      treated with tiotropium in addition to usual care compared with usual care alone
      over a 1-year timeframe. The study was based on resource utilisation in the two
      previously described trials. METHODS: Resource utilisation and clinical data were
      prospectively collected for the two 1-year, randomised, double-blind trials of
      tiotropium plus usual care versus usual care alone (placebo) in 921 patients with
      COPD. Usual care was defined as any medication for COPD used prior to the trial
      except anticholinergics and long-acting beta-adrenoceptor agonists. Medical care
      resource utilisation was recorded at every scheduled visit in each trial. Mean
      total costs were calculated retrospectively by combining the resources utilised
      with the appropriate unit costs (1999 US dollars), excluding study drug
      (tiotropium) costs. RESULTS: Compared with usual care, patients receiving
      tiotropium in addition to usual care had significantly fewer COPD exacerbations
      (20% decrease), hospitalisations (44% reduction) and hospital days (50%
      reduction). Utilisation of resources other than hospitalisation did not differ
      between study groups. As a consequence, patients receiving tiotropium had
      significantly lower mean per- patient costs of hospitalisation compared with
      patients receiving usual care alone (tiotropium US 1,738 dollars +/- US 259
      dollars; placebo US 2,793 dollars +/- US 453 dollars). The mean difference in the
      cost of hospitalisation (resulting from all causes, including COPD) between
      treatment groups was -US 1,056 dollars (95% CI -US 2,078 dollars, -US 34
      dollars), and the difference in total healthcare costs (excluding study drug
      acquisition cost) was -US 1,043 dollars (95% CI -US 2,136 dollars, US 48 dollars)
      in favour of tiotropium. The cost of hospital admissions accounted for 48% of the
      total direct medical costs in this trial. CONCLUSIONS: As hospitalisation is a
      large contributor to the cost of COPD, the addition of tiotropium to usual care
      therapy may have the potential to reduce the economic burden of COPD in a US
      healthcare setting. However, as our study did not consider the acquisition cost
      of tiotropium, further economic evaluation including this cost is needed to
      address whether tiotropium is cost saving compared with usual care (placebo).

PMID- 15250753
TI  - Noise factor analysis for cDNA microarrays.
AB  - A microarray-image model is used that takes into account many factors, including
      spot morphology, signal strength, background fluorescent noise, and shape and
      surface degradation. The model yields synthetic images whose appearance and
      quality reflect that of real microarray images. The model is used to link noise
      factors to the fidelity of signal extraction with respect to a standard image
      extraction algorithm. Of particular interest is the identification of the noise
      factors and their interactions that significantly degrade the ability to
      accurately detect the true gene-expression signal. This study uses statistical
      criteria in conjunction with the simulation of various noise conditions to better
      understand the noise influence on signal extraction for cDNA microarray images.
      It proposes a paradigm that is implemented in software. It specifically considers
      certain kinds of noise in the noise model and sets these at certain levels;
      however, one can choose other types of noise or use different noise levels. In
      sum, it develops a statistical package that can work in conjunction with the
      existing image simulation toolbox.

PMID- 15250752
TI  - Resource use and cost of care for patients hospitalised with community acquired
      pneumonia: impact of adherence to infectious diseases society of america
      guidelines.
AB  - OBJECTIVE: The objective of this study was to compare the inpatient resource use
      and cost of care for patients hospitalised with community-acquired pneumonia
      (CAP) who were treated with preferred antibacterial therapy according to the 1998
      Infectious Diseases Society of America (IDSA) guidelines with those who were not
      treated with preferred therapy. METHODS: A multicentre, observational study was
      conducted in Florida between 1999 and 2000. Hospitalised adult patients (aged >
      or = 18 years) started on antibacterial therapy for suspected or confirmed CAP
      were enrolled in the study. Data collected included patient demographic
      characteristics, pneumonia risk class, resource use (pharmacy, laboratory,
      radiology, respiratory services, hospital room and board) and economic data. Risk
      classification according to Fine et al.'s criteria was determined for each
      patient. Patient's antibacterial therapy was classified as being preferred or non
      preferred according to the 1998 IDSA guidelines. Resource utilisation and cost of
      care were compared between these two groups. RESULTS: Ninety-nine patients were
      enrolled in the study. The average age was 60.6 years +/- 20.5 years. The
      percentage of patients in each risk class (according to Fine et al.) were 11.1%
      in class I, 39.4% in class II, 29.3% in class III, 16.2% in class IV and 4% in
      class V. The mean cost of hospitalisation per admission (excluding physician
      cost) was US 3,490 dollars +/- US 3,058 dollars (median US 2,430 dollars) with
      hospital room/board accounting for the largest percentage (83.7%), followed by
      laboratory (8.1%), antibacterial (4.6%), radiology (2.6%) and respiratory (0.9%)
      cost centres [year 2000 values]. The majority of patients (75.8%) received
      preferred antibacterials according to the IDSA guidelines. The group treated with
      preferred antibacterials had a shorter mean length of hospital stay (4.5 vs 6.8
      days, p = 0.002), a lower total cost of hospitalisation (mean US 3,009 dollars +/
      US 2,682 dollars vs US 4,992 dollars +/- US 3,686 dollars; median US 2,047
      dollars vs US 3,805 dollars, p = 0.021) and lower antibacterial costs (mean US
      117 dollars +/- US 79 dollars vs US 301 dollars +/- US 409 dollars; median US 97
      dollars vs US 171 dollars, p = 0.038) compared with patients who did not receive
      preferred therapy. CONCLUSION: Implementation of protocols according to IDSA
      guidelines may result in cost savings to institutions wishing to reduce the
      economic burden associated with treating hospitalised patients for CAP.

PMID- 15250754
TI  - Wavelet analysis of two-dimensional birefringence images of architectonics in
      biotissues for diagnosing pathological changes.
AB  - A method for polarization filtering, correlation processing, and wavelet analysis
      of coherent images of physiologically normal and necrotically changed (myocardium
      infarct) muscle tissue is presented. A technique for early optical diagnosis of
      the appearance of these biological tissues and the course of their degenerative
      dystrophic changes is proposed.

PMID- 15250755
TI  - Applications of digital image correlation to biological tissues.
AB  - Optical methods are becoming commonplace in investigations of the physical and
      mechanical behavior of biological tissues. Digital image correlation (DIC) is a
      versatile optical method that shows tremendous promise for applications involving
      biological tissues and biomaterials. We present the fundamentals of DIC with an
      emphasis on the application to biological materials. An approach for surface
      preparation is described that facilitates its application to hydrated substrates.
      Three examples are presented that highlight the use of DIC for biomedical
      research. The first example describes the use of DIC to study the mechanical
      behavior of arterial tissues up to 40% elongation. The second example describes
      an evaluation of the mechanical properties of bovine hoof horn in the dehydrated
      and fully hydrated states. Uniaxial tension experiments are performed to
      determine the elastic modulus (E) and Poisson's ratio (nu) of both the arterial
      and dermal tissues. Spatial variations in the mechanical properties are evident
      from the full-field characterization of both tissues. Finally, an application of
      DIC to study the evolution of loosening in cemented total hip replacements is
      described. The noncontact analysis enables measurement of the relative
      displacement between the bone/bone cement and bone cement/prosthesis interfaces.
      Based on the elementary optical arrangement, the simple surface preparation, and
      the ability to acquire displacement/strain measurements over a large range of
      deformation, DIC should serve as a valuable tool for biomedical research. Further
      developments will enable the use of DIC for in vivo applications.

PMID- 15250756
TI  - Estimation of melanin and hemoglobin in skin tissue using multiple regression
      analysis aided by Monte Carlo simulation.
AB  - To estimate the concentrations of melanin and blood and the oxygen saturation in
      human skin tissue, we propose a method using a multiple regression analysis aided
      by a Monte Carlo simulation for diffuse reflectance spectra from the skin tissue.
      By using the absorbance spectrum as a response variable and the extinction
      coefficients of melanin, oxygenated hemoglobin, and deoxygenated hemoglobin as
      predictor variables, the multiple regression analysis gives regression
      coefficients. The concentrations of melanin and blood are determined from the
      regression coefficients using conversion vectors that are estimated numerically
      in advance, while the oxygen saturation is obtained directly from the regression
      coefficients. Numerical and experimental investigations were performed for
      layered skin tissue models and phantoms. Measurements of human skin were also
      carried out to monitor variations in the melanin and blood contents and
      oxygenation during cuff occlusion. The results confirmed the usefulness of the
      proposed method.

PMID- 15250757
TI  - Temperature mapping of laser-induced hyperthermia in an ocular phantom using
      magnetic resonance thermography.
AB  - Laser-induced heating in an ocular phantom is measured with magnetic resonance
      thermography (MRT) using temperature-dependent phase changes in proton resonance
      frequency. The ocular phantom contains a layer of melanosomes isolated from
      bovine retinal pigment epithelium. The phantom is heated by the 806-nm output of
      a continuous wave diode laser with an irradiance of 2.4 to 21.6 W/cm2 in a beam
      radius of 0.8 or 2.4 mm, depending on the experiment. MRT is performed with a 2 T
      magnet, and a two-turn, 6-cm-diam, circular radio frequency coil. Two-dimensional
      temperature gradients are measured within the plane of the melanin layer, as well
      as normal to it, with a temperature resolution of 1 degrees C or better. The
      temperature gradients extending within the melanin layer are broader than those
      orthogonal to the layer, consistent with the higher optical absorption and
      consequent heating in the melanin. The temperature gradients in the phantom
      measured by MRT closely approximate the predictions of a classical heat diffusion
      model. Three-dimensional temperature maps with a spatial resolution of 0.25 mm in
      all directions are also made. Although the temporal resolution is limited in the
      prototype system (22.9 s for a single image "slice"), improvements in future
      implementations are likely. These results indicate that MRT has sufficient
      spatial and temperature resolution to monitor target tissue temperature during
      transpupillary thermotherapy in the human eye.

PMID- 15250758
TI  - Imaging ex vivo and in vitro brain morphology in animal models with ultrahigh
      resolution optical coherence tomography.
AB  - The feasibility of ultrahigh resolution optical coherence tomography (UHR OCT) to
      image ex vivo and in vitro brain tissue morphology on a scale from single neuron
      cells to a whole animal brain was investigated using a number of animal models.
      Sub-2-microm axial resolution OCT in biological tissue was achieved at different
      central wavelengths by separately interfacing two state-of-the-art broad
      bandwidth light sources (titanium:sapphire, Ti:Al2O3 laser, lambdac=800 nm,
      Deltalambda=260 nm, Pout=50 mW and a fiber laser light source, lambdac=1350 nm,
      Deltalambda=470 nm, Pout=4 mW) to free-space or fiber-based OCT systems, designed
      for optimal performance in the appropriate wavelength regions. The ability of sub
      2-microm axial resolution OCT to visualize intracellular morphology was
      demonstrated by imaging living ganglion cells in cultures. The feasibility of UHR
      OCT to image the globular structure of an entire animal brain as well as to
      resolve fine morphological features at various depths in it was tested by imaging
      a fixed honeybee brain. Possible degradation of OCT axial resolution with depth
      in optically dense brain tissue was examined by depositing microspheres through
      the blood stream to various depths in the brain of a living rabbit. It was
      determined that in the 1100 to 1600-nm wavelength range, OCT axial resolution was
      well preserved, even at depths greater than 500 microm, and permitted distinct
      visualization of microspheres 15 microm in diameter. In addition, the OCT image
      penetration depth and the scattering properties of gray and white brain matter
      were evaluated in tissue samples from the visual cortex of a fixed monkey brain.

PMID- 15250759
TI  - Flash lamp-excited time-resolved fluorescence microscope suppresses
      autofluorescence in water concentrates to deliver an 11-fold increase in signal
      to-noise ratio.
AB  - The ubiquity of naturally fluorescing components (autofluorophores) encountered
      in most biological samples hinders the detection and identification of labeled
      targets through fluorescence-based techniques. Time-resolved fluorescence (TRF)
      is a technique by which the effects of autofluorescence are reduced by using
      specific fluorescent labels with long fluorescence lifetimes (compared with
      autofluorophores) in conjunction with time-gated detection. A time-resolved
      fluorescence microscope (TRFM) is described that is based on a standard
      epifluorescence microscope modified by the addition of a pulsed excitation source
      and an image-intensified time-gateable CCD camera. The choice of pulsed
      excitation source for TRFM has a large impact on the price and performance of the
      instrument. A flash lamp with rapid discharge characteristics was selected for
      our instrument because of the high spectral energy in the UV region and short
      pulse length. However, the flash output decayed with an approximate lifetime of
      18 micros and the TRFM required a long-lived lanthanide chelate label to ensure
      that probe fluorescence was visible after decay of the flash plasma. We
      synthesized a recently reported fluorescent chelate (BHHCT) and conjugated it to
      a monoclonal antibody directed against the waterborne parasite Giardia lamblia.
      For a 600-nm bandpass filter set and a gate delay of 60 micros, the TRFM provided
      an 11.3-fold improvement in the signal-to-noise ratio (S/N) of labeled Giardia
      over background. A smaller gain in an SNR of 9.69-fold was achieved with a 420-nm
      longpass filter set; however, the final contrast ratio between labeled cyst and
      background was higher (11.3 versus 8.5). Despite the decay characteristics of the
      light pulse, flash lamps have many practical advantages compared with optical
      chopper wheels and modulated lasers for applications in TRFM.

PMID- 15250760
TI  - Confocal fluorescence microscope with dual-axis architecture and biaxial
      postobjective scanning.
AB  - We present a novel confocal microscope that has dual-axis architecture and
      biaxial postobjective scanning for the collection of fluorescence images from
      biological specimens. This design uses two low-numerical-aperture lenses to
      achieve high axial resolution and long working distance, and the scanning mirror
      located distal to the lenses rotates along the orthogonal axes to produce arc
      surface images over a large field of view (FOV). With fiber optic coupling, this
      microscope can potentially be scaled down to millimeter dimensions via
      microelectromechanical systems (MEMS) technology. We demonstrate a benchtop
      prototype with a spatial resolution < or =4.4 microm that collects fluorescence
      images with a high SNR and a good contrast ratio from specimens expressing GFP.
      Furthermore, the scanning mechanism produces only small differences in
      aberrations over the image FOV. These results demonstrate proof of concept of the
      dual-axis confocal architecture for in vivo molecular and cellular imaging.

PMID- 15250761
TI  - Fast model-free deconvolution of fluorescence decay for analysis of biological
      systems.
AB  - For complex biological systems, conventional analysis of fluorescence intensity
      decay in terms of discrete exponential components cannot readily provide a true
      representation of the underlying fluorescence dynamics. We investigate an
      alternative nonparametric method for the analysis of time-resolved fluorescence
      data from biochemical and biological systems based on the expansion of
      fluorescence decay in a discrete Laguerre basis. We report that a unique Laguerre
      expansion can be found for fluorescence intensity decays of arbitrary form with
      convergence to a correct solution significantly faster than conventional
      multiexponential approximation methods. The Laguerre expansion coefficients are
      shown to be highly correlated with intrinsic fluorescence lifetimes and allow
      direct characterization of the fluorescence dynamics. A novel method for
      prediction of concentrations in mixtures of biochemical components using these
      coefficients is developed and successfully tested (prediction error <2%) using
      data from different mixtures of fluorescence lifetime standards. These findings
      suggest that the use of Laguerre expansion coefficients is a fast approach for
      the characterization and discrimination of complex biological systems such as
      tissues and cells, and that the method has potential for applications of
      fluorescence lifetime techniques to tissue diagnostics and imaging microscopy of
      living cells.

PMID- 15250762
TI  - Interaction of PSD-95 with potassium channels visualized by fluorescence lifetime
      based resonance energy transfer imaging.
AB  - Resonance energy transfer (RET) has been extensively used to estimate the
      distance between two different fluorophores. This study demonstrates how protein
      protein interactions can be visualized and quantified in living cells by time
      correlated single-photon counting (TCSPC) imaging techniques that exploit the RET
      between appropriate fluorescent labels. We used this method to investigate the
      association of the potassium inward rectifier channel Kir2.1 and the neuronal PDZ
      protein PSD-95, which has been implicated in subcellular targeting and clustering
      of ion channels. Our data show that the two proteins not only colocalize within
      clusters but also interact with each other. Moreover, the data allow a spatially
      resolved quantification of this protein-protein interaction with respect to the
      relative number and the proximity between interacting molecules. Depending on the
      subcellular localization, a fraction of 20 to 60% of PSD-95 molecules interacted
      with Kir2.1 channels, approximating their fluorescent labels by less than 5 nm.

PMID- 15250763
TI  - Second-harmonic imaging of cornea after intrastromal femtosecond laser ablation.
AB  - Nonlinear laser scanning microscopy is widely used for noninvasive imaging in
      cell biology and tissue physiology. However, multiphoton fluorescence imaging of
      dense, transparent connective tissue (e.g., cornea) is challenging since
      sophisticated labeling or slicing is necessary. High-resolution, high-contrast
      second harmonic generation (SHG) imaging of corneal tissue based on the intrinsic
      structure of collagen is discussed. The three-dimensional corneal ultrastructure
      in depths up to hundreds of microns can be probed noninvasively, without any
      staining or mechanical slicing. As an important application of second harmonic
      imaging in ophthalmology, the modification of corneal ultrastructure using
      femtosecond laser intrastromal ablation is systematically investigated to
      evaluate next-generation refractive surgical approaches.

PMID- 15250764
TI  - Spectroscopic detection of bladder cancer using near-infrared imaging techniques.
AB  - High-contrast imaging of bladder cancer is demonstrated using near-infrared
      autofluorescence under long-wavelength laser excitation in combination with cross
      polarized elastic light scattering. Fresh unprocessed surgical specimens obtained
      following cystectomy or transurethral resection were utilized and a set of images
      for each tissue sample was recorded. These images were compared with the
      histopathology of the tissue sample. The experimental results indicate that the
      intensity of the near-infrared emission as well as that of the cross-polarized
      backscattered light was considerably different in cancer tissues than in that of
      the contiguous nonneoplastic tissues, allowing an accurate delineation of a
      tumor's margins.

PMID- 15250766
TI  - Detection of myocardial cell damage in isolated rat hearts with near-infrared
      spectroscopy.
AB  - One hallmark of cell death resulting from prolonged ischemia is cell membrane
      disruption. We apply optical spectroscopy to gauge membrane disruption in
      isolated rat hearts by monitoring (1) the washout of myoglobin (Mb) and (2) the
      accumulation of an exogenous contrast agent in permeabilized cells. The contrast
      agent, a neodymium (Nd) chelate, has several absorptions in the visible and near
      IR, and when present in the perfusate, it cannot penetrate cellular membranes.
      When membrane integrity is disrupted, however, it is expected to accumulate
      within the intracellular space; moreover, cellular Mb is expected to wash out. To
      test this hypothesis, rat hearts (n=12) are perfused with Krebs-Henseleit buffer
      (KHB), followed by perfusion with KHB in which a 5 mM Nd-DTPA solution is
      present. Membrane damage is then induced by infusion of digitonin into the Nd-KHB
      perfusate to provide a digitonin concentration of 2.5, 5, or 10 microg/mL. After
      30 min of infusion, Mb levels fall to 46+/-14% of baseline levels and Nd-DTPA
      rises to 161+/-19% of predigitonin levels. No apparent dependence of total
      membrane disruption on digitonin concentration over the concentration range
      studied is found, although higher concentrations do lead to more rapid membrane
      disruption.

PMID- 15250765
TI  - Redox ratio of mitochondria as an indicator for the response of photodynamic
      therapy.
AB  - The effect of photodynamic therapy (PDT) treatment on the metabolic state of
      tumor mitochondria is investigated by imaging of tumor redox status. PDT is
      performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro
      2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG
      induced PDT resulting in a highly oxidized state of tumor mitochondria. This is
      determined from the redox ratio changes derived from the intrinsic oxidized
      flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced
      nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a
      cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable
      and informative measurements of PDT-induced tissue damage. In the PDT treated
      region of the tumor, highly oxidized flavoprotein and diminishing NADH
      fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by
      singlet oxygen produced in the photosensitization process.

PMID- 15250767
TI  - Changes in regional cerebral blood volume in frontal cortex during mental work
      with and without caffeine intake: functional monitoring using near-infrared
      spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) was used to measure frontal regional cerebral
      blood volume (rCBV) in a person whose brain was under the influence of
      pharmacological agents while the person was performing a complex task. Fourteen
      healthy participants were administered Uchida-Kraepelin psychodiagnostic (UKP)
      tests before and after caffeine intake, and the concentration of caffeine in the
      urine was measured. The average number of answers and the average number of
      correct answers given by the participants improved significantly following
      caffeine intake. During the UKP testing, changes in the rCBV in the inferior
      frontal cortex were continuously measured using NIRS. The volume during the rest
      periods decreased as a result of caffeine-induced constriction of the cerebral
      arteriola. The volume increased during the mental work, but the degree of the
      increase was the same before and after caffeine intake. Although the performance
      of the mental work improved following caffeine intake, the improvement was not
      reflected in the rCBV in the inferior frontal cerebral cortex. These results
      suggest that caffeine helps to protect the brain from excessive hyperemia in
      addition to activating the neurons in the prefrontal cortex.

PMID- 15250768
TI  - Non-ionizing near-infrared radiation transillumination spectroscopy for breast
      tissue density and assessment of breast cancer risk.
AB  - There is increasing attention to prevention as a means to reduce cancer
      incidence. Prevention interventions or therapies in turn rely on risk assessment
      programs to identify those women most likely to benefit from education and
      lifestyle changes. These programs are usually based either on interviews to
      identify ethnic, genetic, and lifestyle factors contributing to risk or on
      physical examination of the breast. For the latter it has been shown that the
      parenchymal density pattern observed in X-ray mammography can be used to assess
      an individual's risk. Extensive areas of dense, glandular tissue that are
      relatively radio-opaque are associated with higher breast cancer risk, with an
      odds ratio of 4 to 6 compared with women in whom the breast density is low owing
      to an abundance of adipose tissue. Near-infrared optical transillumination
      spectroscopy has been used previously to investigate the physiological properties
      of breast tissue. In this study, women were recruited who underwent recently X
      ray mammography. The tissue density was assessed by a radiologist. The women then
      underwent optical transillumination spectroscopy, for which an instrument was
      developed that delivered visible and near-infrared light to the breast. After
      being transmitted through the breast craniocaudally in one of four quadrants, the
      spectrum from 625 to 1050 nm was measured. The spectra were used as input to a
      Principal Component Analysis (PCA) that used the corresponding mammographic
      density as the reference standard. The study group consisted of 92 women aged 39
      to 72 years. Without further stratification for age, menopausal status, or
      measurement position, the PCA numerical model predicted the radiological
      assessment of tissue density in the mid 80% to low 90%.

PMID- 15250769
TI  - Nonintrusive, noncontacting frequency-domain photothermal radiometry and
      luminescence depth profilometry of carious and artificial subsurface lesions in
      human teeth.
AB  - Nonintrusive, noncontacting frequency-domain photothermal radiometry (FD-PTR or
      PTR) and frequency-domain luminescence (FD-LUM or LUM) have been used with 659-nm
      and 830-nm laser sources to detect artificial and natural subsurface defects in
      human teeth. The major findings of this study are (1) PTR is sensitive to very
      deep (>5 mm) defects at low modulation frequencies (5 Hz). Both PTR and LUM
      amplitudes exhibit a peak at tooth thicknesses of ca. 1.4 to 2.7 mm. Furthermore,
      the LUM amplitude exhibits a small trough at ca. 2.5 to 3.5 mm. (2) PTR is
      sensitive to various defects such as a deep carious lesion, a demineralized area,
      an edge, a crack, and a surface stain, while LUM exhibits low sensitivity and
      spatial resolution. (3) PTR frequency scans over the surface of a fissure into
      demineralized enamel and dentin show higher amplitude than those for healthy
      teeth, as well as a pronounced curvature in both the amplitude and phase signal
      channels. These can be excellent markers for the diagnosis of subsurface carious
      lesions. (4) PTR amplitude frequency scans over the surface of enamels of
      variable thickness exhibit strong thickness dependence, thus establishing depth
      profilometric sensitivity to subsurface interfaces such as the dentin/enamel
      junction.

PMID- 15250770
TI  - Attenuated total reflection Fourier transform infrared and polarization
      spectroscopy of in vivo human skin ablated, layer by layer, by erbium:YAG laser.
AB  - The results of an experimental study of the possibilities of monitoring erbium
      yttrium aluminum garnet laser-mediated ablation of human epidermis with the use
      of Fourier transform infrared (FTIR) spectroscopy and spectral polarization
      techniques are presented. The attenuated total reflection (ATR) method was used
      for FTIR spectroscopic measurements. Spectral polarization monitoring of the
      ablation was carried out by analyzing the spectra of the degree of residual
      linear polarization of a probe light diffusely reflected from the laser-treated
      region of skin. It was found that the analysis of FTIR spectra allows monitoring
      of the water and protein contents in the subsurface layers of the treated skin,
      while the degree of residual polarization measured at the wavelengths of maximal
      absorption of hemoglobin is sensitive to changes in the epidermis thickness and
      the blood content in the dermal layer (the degree of erythema).

PMID- 15250771
TI  - Low-intensity indocyanine-green laser phototherapy of acne vulgaris: pilot study.
AB  - Near infrared (NIR) diode laser low-intensity (soft) phototherapy with the
      topical application of indocyanine green (ICG) has been suggested for treatment
      of acne vulgaris. Twelve volunteers with acne lesions on their faces and/or backs
      were enrolled in the experiment. Skin areas of the subjects that were 4 x 5 cm2
      were stained with ICG solution for 5 min before laser irradiation (803 nm) at a
      power density up to 50 mW/cm2 for 5 to 10 min. For 75% of the subjects, a single
      treatment was provided and for the other 25%, eight sequential treatments over a
      period of a month were carried out. Observations a month after the completion of
      the treatment showed that only the multiple treatments with a combination of ICG
      and NIR irradiation reduced inflammation and improved the state of the skin for a
      month without any side effects. A month after treatment, the improvement was
      about 80% for the group receiving multiple treatments. Single treatments did not
      have a prolonged effect.

PMID- 15250772
TI  - Design of hearing aid shells by three dimensional laser scanning and mesh
      reconstruction.
AB  - Hearing aid shells (or earmolds) must couple the hearing aid with the user's ear.
      Earmolds have to fit the subject's outer ear canal properly to ensure a good
      performance of the aid. Because of the great variability in the anatomical
      pattern of the ear, earmolds are custom made. At present, an impression of the
      subject's ear canal is taken and used to fabricate the silicon-made mold. The
      postimpression activities that typically are performed during the fabrication
      process modify the physical dimensions of the resulting earmold and thus affect
      the fit of the product. A novel system for 3-D laser scanning and mesh
      reconstruction of the surface of ear canal impressions is presented. The
      reconstructed impression can be digitally stored and passed directly to dedicated
      CAD 3-D printing machines to model the silicon earmold and thus achieve the best
      possible fit. The proposed system is based on a couple of cameras and a
      commercial laser for the surface digitization and on a straightforward algorithm,
      based on the deformation of a geometric model, for the reconstruction of the
      acquired surface. Measurements on objects of well-known geometric features and
      dimensions are performed to assess the accuracy and repeatability levels of this
      3-D acquisition system. Robustness to noise of the proposed reconstruction
      algorithm is determined by simulations with a synthetic test surface. Finally,
      the first measurements (acquisition+reconstruction) of closed surfaces from ear
      canal impressions are reported.

PMID- 15250774
TI  - The separation of hypericin's enantiomers and their photophysics in chiral
      environments.
AB  - We report the first separation of the enantiomers of hypericin. Their steady
      state optical spectra and ultrafast primary photoprocesses are investigated in
      chiral environments. Within experimental error, there is no difference between
      the two enantiomers in any of the systems considered. This is consistent with the
      emerging picture that the rich and extended absorption spectrum of hypericin is
      not a result of ground-state heterogeneity. It is also consistent with the
      observation that the spectra and photophysics of hypericin are generally
      insensitive to environments in which it does not aggregate.

PMID- 15250777
TI  - Sum-difference theory of remembering and knowing: a two-dimensional signal
      detection model.
AB  - In the remember-know paradigm for studying recognition memory, participants
      distinguish items whose presentations are episodically remembered from those that
      are merely familiar. A one-dimensional model postulates that remember responses
      are just high-confidence old judgments, but a meta-analysis of 373 experiments
      shows that the receiver operating characteristic (ROC) curves predicted by this
      model have the wrong slope. According to the new sum-difference Theory of
      remembering and knowing (STREAK), old items differ from new ones in both global
      and specific memory strength: The old-new judgment is based on a weighted sum of
      these dimensions, and the remember- know judgment is based on a weighted
      difference. STREAK accounts for the form of several novel kinds of ROC curves and
      for existing remember-know and item-recognition data.

PMID- 15250778
TI  - Encoder: a connectionist model of how learning to visually encode fixated text
      images improves reading fluency.
AB  - This article proposes that visual encoding learning improves reading fluency by
      widening the span over which letters are recognized from a fixated text image so
      that fewer fixations are needed to cover a text line. Encoder is a connectionist
      model that learns to convert images like the fixated text images human readers
      encode into the corresponding letter sequences. The computational theory of
      classification learning predicts that fixated text-image size makes this learning
      difficult but that reducing image variability and biasing learning should help.
      Encoder confirms these predictions. It fails to learn as image size increases but
      achieves humanlike visual encoding accuracy when image variability is reduced by
      regularities in fixation positions and letter sequences and when learning is
      biased to discover mapping functions based on the sequential, componential
      structure of text. After training, Encoder exhibits many humanlike text
      familiarity effects.

PMID- 15250779
TI  - Reasoning from inconsistency to consistency.
AB  - This article presents a theory of how individuals reason from inconsistency to
      consistency. The theory is based on 3 main principles. First, individuals try to
      construct a single mental model of a possibility that satisfies a current set of
      propositions, and if the task is impossible, they infer that the set is
      inconsistent. Second, when an inconsistency arises from an incontrovertible fact,
      they retract any singularly dubious proposition or any proposition that is
      inconsistent with the fact; otherwise, they retract whichever proposition
      mismatches the fact. A mismatch can arise from a proposition that has only mental
      models that conflict with the fact or fail to represent it. Third, individuals
      use their causal knowledge-in the form of models of possibilities-to create
      explanations of what led to the inconsistency. A computer program implements the
      theory, and experimental results support each of its principles.

PMID- 15250780
TI  - Computing the meanings of words in reading: cooperative division of labor between
      visual and phonological processes.
AB  - Are words read visually (by means of a direct mapping from orthography to
      semantics) or phonologically (by mapping from orthography to phonology to
      semantics)? The authors addressed this long-standing debate by examining how a
      large-scale computational model based on connectionist principles would solve the
      problem and comparing the model's performance to people's. In contrast to
      previous models, the present model uses an architecture in which meanings are
      jointly determined by the 2 components, with the division of labor between them
      affected by the nature of the mappings between codes. The model is consistent
      with a variety of behavioral phenomena, including the results of studies of
      homophones and pseudohomophones thought to support other theories, and
      illustrates how efficient processing can be achieved using multiple simultaneous
      constraints.

PMID- 15250781
TI  - Serial mechanisms in lexical access: the rank hypothesis.
AB  - There is general agreement that the effect of frequency on lexical access time is
      roughly logarithmic, although little attention has been given to the reason for
      this. The authors argue that models of lexical access that incorporate a
      frequency-ordered serial comparison or verification procedure provide an account
      of this effect and predict that the underlying function directly relates access
      time to the rank order of words in a frequency-ordered set. For both group data
      and individual data, it is shown that rank provides a better fit to the data than
      does a function based on log frequency. Extensions to a search model are proposed
      that account for error rates and latencies and the effect of age of acquisition,
      which is interpreted as an effect of cumulative frequency.

PMID- 15250782
TI  - Loss aversion and inhibition in dynamical models of multialternative choice.
AB  - The roles of loss aversion and inhibition among alternatives are examined in
      models of the similarity, compromise, and attraction effects that arise in
      choices among 3 alternatives differing on 2 attributes. R. M. Roe, J. R.
      Busemeyer, and J. T. Townsend (2001) have proposed a linear model in which
      effects previously attributed to loss aversion (A. Tversky & D. Kahneman, 1991)
      arise from attention switching between attributes and similarity-dependent
      inhibitory interactions among alternatives. However, there are several reasons to
      maintain loss aversion in a theory of choice. In view of this, an alternative
      theory is proposed, integrating loss aversion and attention switching into a
      nonlinear model (M. Usher & J. L. McClelland, 2001) that relies on inhibition
      independent of similarity among alternatives. The model accounts for the 3
      effects and makes testable predictions contrasting with those of the Roe et al.
      (2001) model.

PMID- 15250783
TI  - The hazards of underspecified models: the case of symmetry in everyday
      predictions.
AB  - Should one be more confident when predicting the whole (or an event based on a
      larger sample) from the part (or an event based on a smaller sample) than when
      predicting the reverse? The relevant literature on judgment under uncertainty
      argues that such predictions are symmetrical but that, as an empirical matter,
      people often fail to appreciate this symmetry. The authors show that symmetry in
      prediction does not necessarily hold. In addition to an empirical study involving
      predictions about soccer games, they develop a theoretical model showing that, at
      least for the ranges of numerical values usually found in everyday judgment
      problems, symmetry in predictions is uncommon when 2 different sample sizes are
      involved. The complexity of the theoretical model used in this analysis raises
      questions about model specification in judgmental research.

PMID- 15250784
TI  - Objectivity in the eye of the beholder: divergent perceptions of bias in self
      versus others.
AB  - Important asymmetries between self-perception and social perception arise from
      the simple fact that other people's actions, judgments, and priorities sometimes
      differ from one's own. This leads people not only to make more dispositional
      inferences about others than about themselves (E. E. Jones & R. E. Nisbett, 1972)
      but also to see others as more susceptible to a host of cognitive and
      motivational biases. Although this blind spot regarding one's own biases may
      serve familiar self-enhancement motives, it is also a product of the
      phenomenological stance of naive realism. It is exacerbated, furthermore, by
      people's tendency to attach greater credence to their own introspections about
      potential influences on judgment and behavior than they attach to similar
      introspections by others. The authors review evidence, new and old, of this
      asymmetry and its underlying causes and discuss its relation to other
      psychological phenomena and to interpersonal and intergroup conflict.

PMID- 15250785
TI  - Context noise and item noise jointly determine recognition memory: a comment on
      Dennis and Humphreys (2001).
AB  - S. Dennis and M. S. Humphreys (see record 2001-17194-007) proposed a model with
      the strict assumption that recognition memory is not affected by interference
      from other items. Instead, confusions are due to noise generated by prior
      contexts in which the test item appeared. This model seems disparate from
      existing models of recognition memory but is similar in many ways that are not
      superficially obvious. One difference is the order in which item and context
      information are used as retrieval cues. A more critical difference is the
      assertion that only an item's history, and not other items, affects recognition
      memory. Conceptual arguments along with the results of 2 experiments make a
      persuasive case that both types of noise affect recognition. To illustrate the
      approach, the authors fit experimental data with a version of the retrieving
      effectively from memory model (R. M. Shiffrin & M. Steyvers, 1997) incorporating
      both sources of noise.

PMID- 15250786
TI  - Does elevated power lead to approach and reduced power to inhibition? Comment on
      Keltner, Gruenfeld, and Anderson (2003).
AB  - D. Keltner, D. H. Gruenfeld, and C. Anderson (see record 2003-00307-004) stated a
      set of propositions postulating independent effects for elevated power and
      reduced power. The present commentary argues that past studies have permitted
      examining the opposite effects but not the specific effects of high and low
      power. Suggestions are made for improving designs and formulating analytic
      strategies that would permit evaluating the specific assertions that elevated
      power increases approach and reduced power increases inhibition.

PMID- 15250787
TI  - The I of the storm-relations between self and conscious emotion experience:
      comment on Lambie and Marcel (2002).
AB  - J. A. Lambie and A. J. Marcel (2002) outlined a framework for understanding
      varieties of conscious emotion experience. In their analysis, the self plays an
      important role in conscious emotion experience. In this critique, however, the
      authors propose that Lambie and Marcel's presentation of the self needs further
      specification if it is to account for varieties of conflicted emotional
      experience, particularly those characteristic of dissociative states. The authors
      propose that a more elaborated self-construct is necessary to account for these
      phenomena involving either the "splitting off of significant self-related
      concerns or the existence of multiple self-constructs. These arguments are
      illustrated by clinical and subclinical case examples.

PMID- 15250788
TI  - How many selves in emotion experience? Reply to Dalgleish and Power (2004).
AB  - T. Dalgleish and M. J. Power (see record 2004-15929-012) suggest that J. A.
      Lambie and A. J. Marcel's (2002) article implicitly presents a unitary view of
      self in emotion experience and propose that certain clinical phenomena require
      multiple selves. This reply summarizes Lambie and Marcel's usages of the term
      self and examines both Dalgleish and Power's gloss of these and their own usages.
      This indicates that their own central usage of the term misrepresents Lambie and
      Marcel and is itself an improper usage. More important, examination of the
      phenomena claimed to require multiple selves suggests that they do not and that
      Dalgleish and Power may have misread the relevant clinical literature. Finally,
      Lambie and Marcel's own conception of dissociative phenomena and multiple selves
      are outlined, and alternative approaches are sketched. In discussing the usages
      of the term self and interpretation of cognitive and affective disorders, this
      reply attempts to clarify certain confusions.

PMID- 15250789
TI  - Contextual moderation of racial bias: the impact of social roles on controlled
      and automatically activated attitudes.
AB  - Three experiments tested the hypothesis that the social roles implied by specific
      contexts can attenuate or reverse the typical pattern of racial bias obtained on
      both controlled and automatic evaluation measures. Study 1 assessed evaluations
      of Black and Asian faces in contexts related to athlete or student roles. Study 2
      compared evaluations of Black and White faces in 3 role-related contexts
      (prisoner, churchgoer, and factory worker). Study 3 manipulated role cues (lawyer
      or prisoner) within the same prison context. All 3 studies produced significant
      reversals of racial bias as a function of implied role on measures of both
      controlled and automatic evaluation. These results support the interpretation
      that differential evaluations based on Race x Role interactions provide one way
      that context can moderate both controlled and automatic racial bias.

PMID- 15250790
TI  - Goal contagion: perceiving is for pursuing.
AB  - Six studies examined the goal contagion hypothesis, which claims that individuals
      may automatically adopt and pursue a goal that is implied by another person's
      behavior. Participants were briefly exposed to behavioral information implying a
      specific goal and were then given the opportunity to act on the goal in a
      different way and context. Studies 1-3 established the goal contagion phenomenon
      by showing that the behavioral consequences of goal contagion possess features of
      goal directedness: (a) They are affected by goal strength, (b) they have the
      quality of goal appropriateness, and (c) they are characterized by persistence.
      Studies 4-6 show that people do not automatically adopt goals when the observed
      goal pursuit is conducted in an unacceptable manner, because the goal will then
      be perceived as unattractive. The results are discussed in the context of recent
      research on automatic goal pursuits.

PMID- 15250791
TI  - Stereotype threat and performance: how self-stereotypes influence processing by
      inducing regulatory foci.
AB  - The authors hypothesized that activated self-stereotypes can influence the
      strategies of task solution by inducing regulatory foci. More specifically,
      positive self-stereotypes should induce a promotion focus state of eagerness,
      whereas negative stereotypes should induce a prevention focus state of vigilance.
      Study 1 showed that a negative ascribed stereotype with regard to task
      performance leads to better recall for avoidance-related statements whereas a
      positive stereotype leads to better recall for approach-related statements. In
      Studies 2 and 3, both an experimental manipulation of group performance
      expectation and the preexisting stereotype of better verbal skills in women than
      in men led to faster and less accurate performance in the positive as compared
      with the negative stereotype group. Studies 4 and 5 showed that positive in-group
      stereotypes led to more creative performance whereas negative stereotypes led to
      better analytical performance. These results point to a possible mechanism for
      stereotype-threat effects.

PMID- 15250792
TI  - Is it culture or is it language? Examination of language effects in cross
      cultural research on categorization.
AB  - Differences in reasoning styles between Chinese and European Americans held even
      when controlling for the language of testing. Bilingual Chinese organized objects
      in a more relational and less categorical way than European Americans, whether
      tested in English or in Chinese. Thus, culture affects categorization independent
      of the testing language. Nevertheless, language affected some Chinese bilinguals'
      categorization. The responses of Chinese from the Mainland and Taiwan were more
      relational when tested in Chinese than when tested in English. Responses of
      Chinese from Hong Kong and Singapore were equally relational when tested in
      Chinese and in English. Age and context of learning English are discussed to
      explain the differential language effects among different Chinese groups.
      Theoretical and methodological implications are discussed.

PMID- 15250793
TI  - Group belongingness and procedural justice: social inclusion and exclusion by
      peers affects the psychology of voice.
AB  - The authors focus on the relation between group membership and procedural
      justice. They argue that whether people are socially included or excluded by
      their peers influences their reactions to unrelated experiences of procedural
      justice. Findings from 2 experiments corroborate the prediction that reactions to
      voice as opposed to no-voice procedures are affected more strongly when people
      are included in a group than when they are excluded from a group. These findings
      are extended with a 3rd experiment that shows that people who generally
      experience higher levels of inclusion in their lives respond more strongly to
      voice as opposed to no-voice procedures. It is concluded that people's reactions
      to procedural justice are moderated by people's level of inclusion in social
      groups.

PMID- 15250794
TI  - Feeling better about doing worse: social comparisons within romantic
      relationships.
AB  - The authors examined the role of closeness between self and partner in
      determining the impact of social comparisons within intimate relationships. To
      the extent that one's partner is a central aspect of one's identity, one may be
      able to restore one's positive self-regard following an upward comparison with
      the partner by turning to the relationship as a self-affirmational resource.
      Studies 1 and 2 examined reactions to imagined comparisons; Studies 3 and 4
      examined reactions to actual comparison feedback. Across studies, closeness
      moderated the impact of upward comparisons with the partner; that is, higher
      closeness participants responded to a more successful partner by focusing on
      their relationship-related strengths. However, closeness did not moderate the
      impact of downward comparisons with the partner.

PMID- 15250795
TI  - Ethnic enclaves and the dynamics of social identity on the college campus: the
      good, the bad, and the ugly.
AB  - The effects of membership in ethnic organizations and fraternities and sororities
      on intergroup attitudes were examined using a 5-wave panel study at a major,
      multiethnic university. The results showed that these effects were similar for
      both minority and White students. Membership in ethnic student organizations for
      minorities and Greek organizations for Whites was anteceded by the degree of
      one's ethnic identity, and the effects of membership in these groups were
      similar, although not identical, for both White and minority students. These
      effects included an increased sense of ethnic victimization and a decreased sense
      of common identity and social inclusiveness. Consistent with social identity
      theory, at least a portion of these effects were mediated by social identity
      among both White and minority students.

PMID- 15250796
TI  - When do the stigmatized make attributions to discrimination occurring to the self
      and others? The roles of self-presentation and need for control.
AB  - Two experiments examined how the goals of self-presentation and maintenance of
      control over one's outcomes influence women's tendencies to make or to avoid
      making attributions to discrimination. Demonstrating the importance of self
      presentational goals, Experiment 1 showed that targets of discrimination were
      just as likely as similar others to make attributions to discrimination under
      private reporting conditions, but they were significantly less likely to do so
      under public reporting conditions. This experiment also provided initial evidence
      that need for personal control increases discrimination attributions. Experiment
      2 demonstrated that targets' minimization of discrimination, observed in public
      reporting conditions, was eliminated when the need to reassert personal control
      was induced. Both experiments also demonstrated that failing to view events as
      discrimination has negative psychological costs.

PMID- 15250797
TI  - e-Perceptions: personality impressions based on personal websites.
AB  - This research examined the accuracy of personality impressions based on personal
      websites, a rapidly growing medium for self-expression, where identity claims are
      predominant. Eighty-nine websites were viewed by 11 observers, who rated the
      website authors' personalities. The ratings were compared with an accuracy
      criterion (self- and informant reports) and with the authors' ideal-self ratings.
      The websites elicited high levels of observer consensus and accuracy, and
      observers' impressions were somewhat enhanced for Extraversion and Agreeableness.
      The accuracy correlations were comparable in magnitude to those found in other
      contexts of interpersonal perception and generally stronger than those found in
      zero-acquaintance contexts. These findings suggest that identity claims are used
      to convey valid information about personality.

PMID- 15250798
TI  - The relationship between self-esteem level, self-esteem stability, and
      cardiovascular reactions to performance feedback.
AB  - The authors examined the notion that individuals with unstable high self-esteem
      possess implicit self-doubt. They adopted the framework of the biopsychosocial
      model of challenge and threat and assessed spontaneous cardiovascular reactions
      in the face of success versus failure performance feedback. Study 1 revealed
      predicted interactions between feedback condition, self-esteem level, and self
      esteem stability, such that participants with unstable high self-esteem exhibited
      relative threat (a negative reaction) in the failure condition, whereas those
      with stable high self-esteem exhibited relative challenge (a positive reaction).
      Study 2 replicated these results and provided additional evidence against
      plausible alternative explanations.

PMID- 15250799
TI  - Positive geotaxis in infant rats (Rattus norvegicus): a natural behavior and a
      historical correction.
AB  - Infant rats (Rattus norvegicus) placed on a shallow incline (2 degrees, 4
      degrees, or 8 degrees) oriented and moved downhill within 1 min; that is, they
      displayed positive geotaxis. Their downhill translocation increased with angle of
      inclination. A variety of possible behavioral elements (e.g., initial
      orientation, rotational movements, ambulatory velocities) were eliminated as
      explanations of the geotaxis. Wall contact was recognized as a determinative
      event: Pups on the inclines showed no orientation with respect to the
      geogravitational stimulus before contacting a wall. The event of wall contact,
      however, evoked reliable downhill orientation and more linear movements. Positive
      geotaxis was created by pups' orientation against walls and an associated
      increase in movement velocity. This is a distinct perspective on a behavioral
      response that replaces a traditionally misinterpreted phenomenon. The authors
      discuss the ecological validity and historical context of these findings.

PMID- 15250800
TI  - Socially learned preferences for differentially rewarded tokens in the brown
      capuchin monkey (Cebus apella).
AB  - Social learning is assumed to underlie traditions, yet evidence indicating social
      learning in capuchin monkeys (Cebus apella), which exhibit traditions, is sparse.
      The authors tested capuchins for their ability to learn the value of novel tokens
      using a previously familiar token-exchange economy. Capuchins change their
      preferences in favor of a token worth a high-value food reward after watching a
      conspecific model exchange 2 differentially rewarded tokens, yet they fail to
      develop a similar preference after watching tokens paired with foods in the
      absence of a conspecific model. They also fail to learn that the value of
      familiar tokens has changed. Information about token value is available in all
      situations, but capuchins seem to pay more attention in a social situation
      involving novel tokens.

PMID- 15250801
TI  - Recognizing impossible object relations: intuitions about support in chimpanzees
      (Pan troglodytes).
AB  - Using looking-time measures, the authors examined untrained chimpanzees' (Pan
      troglodytes) ability to distinguish between adequate and inadequate support. In 3
      experiments, the chimpanzees' sensitivity to different support relations between
      2 objects was assessed. In each experiment, the chimpanzees saw a possible and an
      impossible test event, presented as digital video clips. Looking times in the 3
      experiments suggest that chimpanzees use amount of contact between 2 objects, but
      not type of contact, to distinguish between adequate and inadequate support
      relations. These results indicate that chimpanzees have some intuition about
      support phenomena but their sensitivity to relational object properties may
      differ from that of human infants (Homo sapiens) in this domain.

PMID- 15250802
TI  - Play signaling and the perception of social rules by juvenile chimpanzees (Pan
      troglodytes).
AB  - Prescriptive social rules are enforced statistical regularities. The authors
      investigated whether juvenile chimpanzees (Pan troglodytes) recognize and use
      enforced statistical regularities to guide dyadic play behavior. They
      hypothesized (a) that proximity of adults, especially mothers of younger play
      partners, to play bouts will increase the play signaling of older partners and
      (b) that when juvenile-juvenile play bouts occur in proximity to adults, older
      partners will play at a lower intensity than when no adults are present. They
      found that older and younger partners increase their play signaling in the
      presence of the mothers of younger partners, particularly as the intensity of
      play bouts increases. In contrast to their hypothesis, older partners played more
      roughly when the mothers of younger partners were in proximity. These results
      suggest that juvenile chimpanzees increase play signaling to prevent termination
      of the play bouts by mothers of younger partners.

PMID- 15250803
TI  - Bottlenosed dolphins (Tursiops truncatus) comprehend the referent of both static
      and dynamic human gazing and pointing in an object-choice task.
AB  - The authors tested 2 bottlenosed dolphins (Tursiops truncatus) for their
      understanding of human-directed gazing or pointing in a 2-alternative object
      choice task. A dolphin watched a human informant either gazing at or pointing
      toward 1 of 2 laterally placed objects and was required to perform a previously
      indicated action to that object. Both static and dynamic gaze, as well as static
      and dynamic direct points and cross-body points, yielded errorless or nearly
      errorless performance. Gaze with the informant's torso obscured (only the head
      was shown) produced no performance decrement, but gaze with eyes only resulted in
      chance performance. The results revealed spontaneous understanding of human gaze
      accomplished through head orientation, with or without the human informant's eyes
      obscured, and demonstrated that gaze-directed cues were as effective as point
      directed cues in the object-choice task.

PMID- 15250804
TI  - Modified prenatal sensory stimulation influences postnatal behavioral and
      perceptual responsiveness in bobwhite quail chicks (Colinus virginianus).
AB  - Asynchronous bimodal stimulation during prenatal development elicits higher
      levels of behavioral and physiological arousal in precocial avian embryos than
      does unimodal sensory stimulation. To investigate whether the increased arousal
      associated with prenatal bimodal stimulation has enduring effects into postnatal
      development, bobwhite quail (Colinus virginianus) embryos received no
      supplemental stimulation, unimodal auditory stimulation, or bimodal (audiovisual)
      stimulation prior to hatching. Embryos exposed to concurrent bimodal stimulation
      demonstrated greater levels of behavioral activity and failed to use maternal
      visual cues to successfully direct species-specific perceptual preferences
      following hatching. These results provide initial evidence that asynchronous
      bimodal sensory stimulation during prenatal development can have enduring effects
      on early postnatal behavioral arousal and perceptual responsiveness and suggest
      that developmental limitations on prenatal sensory stimulation play an important
      role in the emergence of species-typical behavior.

PMID- 15250805
TI  - Direct social contacts override auditory information in the song-learning process
      in starlings (Sturnus vulgaris).
AB  - Social influence on song acquisition was studied in 3 groups of young European
      starlings raised under different social conditions but with the same auditory
      experience of adult song. Attentional focusing on preferred partners appears the
      most likely explanation for differences found in song acquisition in relation to
      experience, sex, and song categories. Thus, pair-isolated birds learned from each
      other and not from broadcast live songs, females did not learn from the adult
      male tutors, and sharing occurred more between socially associated peers. On the
      contrary, single-isolated birds clearly copied the adult songs that may have been
      the only source of attention stimulation. Therefore, social preference appears as
      both a motor for song learning and a potential obstacle for acquisition from
      nonpreferred partners, including adults.

PMID- 15250806
TI  - Visual kin recognition and family resemblance in chimpanzees (Pan troglodytes).
AB  - The male-offspring biased visual kin recognition in chimpanzees (Pan troglodytes)
      reported by L. A. Parr and F. B. M. de Waal (1999) was replicated with human
      (Homo sapiens) participants and a principal components analysis (PCA) of pixel
      maps of the chimpanzee face photos. With the same original materials and methods,
      both humans and the PCA produced the same asymmetry in kin recognition as found
      with the chimpanzees. The PCA suggested that the asymmetry was a function of
      differences in the distribution of global characteristics associated with the
      framing of the faces in the son and daughter test sets. Eliminating potential
      framing biases, either by cropping the photos tightly to the faces or by
      rebalancing the recognition foils, eliminated the asymmetry but not human
      participants' ability to recognize chimpanzee kin.

PMID- 15250807
TI  - Use of visual, acoustic, and olfactory information during embedded invertebrate
      foraging in brown capuchins (Cebus apella).
AB  - Experiments were conducted to investigate which sensory cues are used by brown
      capuchins (Cebus apella) in embedded invertebrate foraging. The importance of
      visual, olfactory, and acoustic cues in such foraging was determined by
      presenting subjects with a stimulus log modified to block out given sensory cues.
      Experiment 1 was designed to investigate whether subjects could locate an
      invertebrate embedded in wood when only visual, acoustic, or olfactory
      information was available. Experiments 2 and 3 were designed to investigate
      extractive foraging behavior when two sensory cues were provided. It was
      hypothesized that the combination of visual and acoustic information would be
      necessary for subjects to successfully locate embedded invertebrates. Results
      indicated that subjects' performance was most successful when both visual and
      acoustic information was available.

PMID- 15250808
TI  - Encoding of geometric and featural spatial information by goldfish (Carassius
      auratus).
AB  - Goldfish (Carassius auratus) were trained in different place-finding tasks as a
      means of analyzing their ability to encode the geometric and the featural
      properties of the environment. Results showed that goldfish could encode and use
      both geometric and featural information to navigate. Goldfish trained in a
      maplike, or relational, procedure encoded both types of information in a single
      representation. In contrast, fish trained in a directly cued procedure developed
      2 independent and competing strategies. These results suggest that the geometric
      properties of the spatial arrangement and discrete landmarks are sensitive to
      encoding in a maplike or relational system, whereas different sources of spatial
      information are encoded in a single and flexible representation of the
      environment.

PMID- 15250809
TI  - Spatial ability and home-range size: examining the relationship in Western men
      and women (Homo sapiens).
AB  - In mammals, spatial sex differences may have coevolved with sex differences in
      the size of home ranges. This study first evaluated whether, in keeping with most
      mammals and traditional human (Homo sapiens) societies, home ranges are larger in
      male than in female Westerners. Second, it established whether navigation
      patterns are associated with a broader set of spatial abilities in men than in
      women. Results showed that current male home ranges surpass female home ranges.
      Ranging was also positively correlated with achievement in tests of mental
      rotation, surface development, and location memory among men only, whereas it was
      associated with embedded figures scores in both sexes. Overall, these findings
      substantiate the adaptive role of several spatial sex differences in humans.

PMID- 15250810
TI  - Inferences about the location of food in the great apes (Pan paniscus, Pan
      troglodytes, Gorilla gorilla, and Pongo pygmaeus).
AB  - Bonobos (Pan paniscus; n = 4), chimpanzees (Pan troglodytes; n = 12), gorillas
      (Gorilla gorilla; n = 8), and orangutans (Pongo pygmaeus; n = 6) were presented
      with 2 cups (1 baited) and given visual or auditory information about their
      contents. Visual information consisted of letting subjects look inside the cups.
      Auditory information consisted of shaking the cup so that the baited cup produced
      a rattling sound. Subjects correctly selected the baited cup both when they saw
      or heard the food. Nine individuals were above chance in both visual and auditory
      conditions. More important, subjects as a group selected the baited cup when only
      the empty cup was either shown or shaken, which means that subjects chose
      correctly without having seen or heard the food (i.e., inference by exclusion).
      Control tests showed that subjects were not more attracted to noisy cups, avoided
      shaken noiseless cups, or learned to use auditory information as a cue during the
      study. It is concluded that subjects understood that the food caused the noise,
      not simply that the noise was associated with the food.

PMID- 15250811
TI  - An assessment of generalization of imitation in two enculturated orangutans
      (Pongo pygmaeus).
AB  - Deferred imitation of object-related actions and generalization of imitation to
      similar but not identical tasks were assessed in two human-reared (enculturated)
      orangutans (Pongo pygmaeus). Each ape displayed low levels of deferred imitation
      but did not provide evidence of generalization of imitation. Results suggest that
      enculturated orangutans may not possess social-cognitive abilities similar to
      that which enculturated chimpanzees are assumed to possess.

PMID- 15250812
TI  - Psychophysiology of aggression, psychopathy, and conduct problems: a meta
      analysis.
AB  - A meta-analysis of 95 studies was conducted to investigate the relations of heart
      rate (HR) and electrodermal activity (EDA) with aggression, psychopathy, and
      conduct problems. Analyses revealed a complex constellation of interactive
      effects, with a failure in some cases of autonomic patterns to generalize across
      antisocial spectrum behavior constructs. Low resting EDA and low task EDA were
      associated with psychopathy/sociopathy and conduct problems. However, EDA
      reactivity was positively associated with aggression and negatively associated
      with psychopathy/sociopathy. Low resting HR and high HR reactivity were
      associated with aggression and conduct problems. Physiology--behavior relations
      varied with age and stimulus valence in several cases. Empirical and clinical
      implications are discussed.

PMID- 15250813
TI  - Individual differences in working memory capacity and dual-process theories of
      the mind.
AB  - Dual-process theories of the mind are ubiquitous in psychology. A central
      principle of these theories is that behavior is determined by the interplay of
      automatic and controlled processing. In this article, the authors examine
      individual differences in the capacity to control attention as a major
      contributor to differences in working memory capacity (WMC). The authors discuss
      the enormous implications of this individual difference for a host of dual
      process theories in social, personality, cognitive, and clinical psychology. In
      addition, the authors propose several new areas of investigation that derive
      directly from applying the concept of WMC to dual-process theories of the mind.

PMID- 15250814
TI  - The role of person versus situation in life satisfaction: a critical examination.
AB  - Two main theoretical approaches have been put forward to explain individual
      differences in life satisfaction: top-down (i.e., personological) and bottom-up
      (i.e., situational). The authors examine the relative merit of these 2 approaches
      and the psychological processes underlying top-down models. Consistent with a top
      down approach, meta-analytic findings indicate that Neuroticism, Extraversion,
      Agreeableness, and Conscientiousness are related to both various domain
      satisfactions and life satisfaction; however, consistent with a bottom-up
      approach, domain satisfactions are strongly linked to life satisfaction but only
      weakly linked to each other. Path analyses based on meta-analytic estimates did
      not support a simple "direct-effects" top-down model but supported both (a) a
      temperament-based top-down model and (b) an integrative model that incorporates
      the direct influence of domain satisfactions on life satisfaction.

PMID- 15250816
TI  - Psychotherapy process: the missing link: comment on Westen, Novotny, and Thompson
      Brenner (2004).
AB  - In this comment, J. S. Ablon and C. Marci argue that focusing on the empirical
      validation of manualized treatment packages misses important information about
      what is efficacious about a given treatment. Psychotherapy process has
      demonstrated that treatments may promote change in ways other than their
      underlying theories claim. Manualized therapies may appear distinct despite
      important similarities in dyadic interaction. These functional similarities in
      the emergent transactional process between therapist and patient may help explain
      the difficulty demonstrating differential outcomes across brands of brief
      therapy. Rather than focus on treatment packages targeting patient
      symptomatology, the authors recommend a shift in focus to the empirical
      validation of change processes coconstructed by therapist and patient in
      naturalistic settings.

PMID- 15250817
TI  - The empirical status of empirically supported psychotherapies: assumptions,
      findings, and reporting in controlled clinical trials.
AB  - This article provides a critical review of the assumptions and findings of
      studies used to establish psychotherapies as empirically supported. The attempt
      to identify empirically supported therapies (ESTs) imposes particular assumptions
      on the use of randomized controlled trial (RCT) methodology that appear to be
      valid for some disorders and treatments (notably exposure-based treatments of
      specific anxiety symptoms) but substantially violated for others. Meta-analytic
      studies support a more nuanced view of treatment efficacy than implied by a
      dichotomous judgment of supported versus unsupported. The authors recommend
      changes in reporting practices to maximize the clinical utility of RCTs, describe
      alternative methodologies that may be useful when the assumptions underlying EST
      methodology are violated, and suggest a shift from validating treatment packages
      to testing intervention strategies and theories of change that clinicians can
      integrate into empirically informed therapies.

PMID- 15250818
TI  - On the need for a new psychotherapy research paradigm: comment on Westen,
      Novotny, and Thompson-Brenner (2004).
AB  - Basic, process, and outcome research have the potential to inform clinical
      practice. However, as D. Westen, C. M. Novotny, and H. Thompson-Brenner observed
      in their timely analysis, the current dominant paradigm for psychotherapy outcome
      research--the randomized clinical trial--is not fulfilling this potential. The
      field's reliance on the medical model and manual-based interventions has
      contributed to the gap between research and clinical practice. Greater
      collaboration between practitioners and researchers, a focus on therapeutic
      principles rather than treatment packages, and systemic changes in how scholarly
      efforts are reinforced are needed to shift the current research paradigm.

PMID- 15250819
TI  - A healthy dose of criticism for randomized trials: comment on Westen, Novotny,
      and Thompson-Brenner (2004).
AB  - D. Westen, C. M. Novotny, and H. Thompson-Brenner identified many important
      concerns in their critique of methods typically used in randomized controlled
      trials (RCTs) of psychotherapy outcome and by extension in methods of identifying
      empirically supported therapies (ESTs). Some of the concerns would be mitigated
      if empirical support of treatments were assessed multidimensionally (separating
      favorability of results from definitiveness of research methods used) and
      continuously rather than categorically. Other concerns can and should be
      addressed within the existing framework of RCTs and ESTs, including consideration
      of inclusion criteria other than a single Axis I condition, experimental
      evaluation of some of the procedural assumptions codified in psychotherapy
      manuals, and far more detailed reporting of RCT results.

PMID- 15250815
TI  - Psychological stress and the human immune system: a meta-analytic study of 30
      years of inquiry.
AB  - The present report meta-analyzes more than 300 empirical articles describing a
      relationship between psychological stress and parameters of the immune system in
      human participants. Acute stressors (lasting minutes) were associated with
      potentially adaptive upregulation of some parameters of natural immunity and
      downregulation of some functions of specific immunity. Brief naturalistic
      stressors (such as exams) tended to suppress cellular immunity while preserving
      humoral immunity. Chronic stressors were associated with suppression of both
      cellular and humoral measures. Effects of event sequences varied according to the
      kind of event (trauma vs. loss). Subjective reports of stress generally did not
      associate with immune change. In some cases, physical vulnerability as a function
      of age or disease also increased vulnerability to immune change during stressors.

PMID- 15250821
TI  - Development of a chimaeric receptor approach to study signalling by tumour
      necrosis factor receptor family members.
AB  - Members of the tumour necrosis factor receptor family play a pivotal role in cell
      differentiation, function and apoptosis. However, signalling by many members of
      the family remains to be elucidated. In the present study, we developed a
      chimaeric receptor approach for studying signalling by receptors belonging to
      this family. The chimaeric receptor comprises the human Fas external domain
      linked to the transmembrane and cytoplasmic domains of a tumour necrosis factor
      receptor family member of interest. When the chimaera is expressed in mouse
      cells, the clustering of the chimaera induced by a human Fas-activating antibody
      activates the intracellular domain of the chimaera without affecting its
      endogenous counterpart. Since the antibody recognizes only human Fas, this
      approach can be used to dissect signalling by any tumour necrosis factor family
      member using any type of mouse cell including those endogenously expressing Fas.
      Moreover, we also showed that the chimaeric receptor approach can be used to
      study signalling at any stage of cell differentiation or function.

PMID- 15250822
TI  - Two new FUT2 (fucosyltransferase 2 gene) missense polymorphisms, 739G-->A and
      839T-->C, are partly responsible for non-secretor status in a Caucasian
      population from Northern Portugal.
AB  - Secretor status is defined by the expression of H type 1 antigen on gastric
      surface epithelium and external secretions. The H type 1 structure, and other
      fucosylated carbohydrates (Le(a), sialyl-Le(a), Le(b), Le(x), sialyl-Le(x) and
      Le(y)), can serve as ligands for several pathogens, including Helicobacter
      pylori, and are cancer-associated antigens. Secretor individuals are more
      susceptible to some bacterial and viral infections of the genito-urinary and
      digestive tracts. The aim of the present study was to examine FUT2
      (fucosyltransferase 2 gene) polymorphisms in a Caucasian population of non
      secretor individuals (n=36) from northern Portugal and to evaluate the activity
      of the mutant FUT2 enzymes. The secretor status was determined by UEAI [Ulex
      europaeus (gorse) lectin] histochemistry in gastric mucosa, and FUT2
      polymorphisms were studied by restriction-fragment-length polymorphism and direct
      sequencing. The majority of non-secretors (88.9%) were homozygous for 428G-->A
      polymorphism; 5.6% were homozygous for 571C-->T and 5.6% were homozygous for two
      new missense polymorphisms, 739G-->A (2.8%) and 839T-->C (2.8%). By kinetic
      studies it was demonstrated that the two new FUT2 mutants (739G-->A and 839T-->C)
      are almost inactive and are responsible for some non-secretor cases.

PMID- 15250824
TI  - C-terminus of mitotic centromere-associated kinesin (MCAK) inhibits its lattice
      stimulated ATPase activity.
AB  - Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT)-destabilizing
      molecular motor. In the present study we show that the final 8 amino acids of the
      C-terminus of MCAK inhibit lattice-stimulated ATPase activity of the motor.
      Surprisingly, loss of this C-terminal 'tail' (MCAK-Q710) leads to more rapid
      depolymerization of MTs relative to full-length MCAK (wt-MCAK). Biochemical and
      microscopic assays revealed that MCAK-Q710 bound to the MT lattice with higher
      apparent affinity as compared with wt-MCAK. End-stimulated depolymerization was
      similar for both enzymes. These data suggest that lattice-bound MCAK can increase
      the rate of MT depolymerization, but at an energy cost. The function of the C
      terminus of MCAK may be to selectively inhibit lattice-stimulated ATPase
      activity, resulting in limited interactions of the motor with the MT lattice.
      This increases the coupling between ATP hydrolysis and tubulin dimer release, but
      it also limits MT depolymerization.

PMID- 15250823
TI  - The strong efficiency of the Escherichia coli gapA P1 promoter depends on a
      complex combination of functional determinants.
AB  - The Escherichia coli multi-promoter region of the gapA gene ensures a high level
      of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) production under various
      growth conditions. In the exponential phase of growth, gapA mRNAs are mainly
      initiated at the highly efficient gapA P1 promoter. In the present study, by
      using site-directed mutagenesis and chemical probing of the RPo (open complex)
      formed by Esigma70 (holoenzyme associated with sigma70) RNAP (RNA polymerase) at
      promoter gapA P1, we show that this promoter is an extended -10 promoter that
      needs a -35 sequence for activity. The -35 sequence compensates for the presence
      of a suboptimal -10 hexamer. A tract of thymine residues in the spacer region,
      which is responsible for a DNA distortion, is also required for efficient
      activity. We present the first chemical probing of an RPo formed at a promoter
      needing both a -10 extension and a -35 sequence. It reveals a complex array of
      RNAP-DNA interactions. In agreement with the fact that residue A-11 in the non
      template strand is flipped out in a protein pocket in previously studied RPos,
      the corresponding A residue in gapA P1 promoter is protected in RPo and is
      essential for activity. However, in contrast with some of the previous findings
      on RPos formed at other promoters, the -12 A:T pair is opened. Strong contacts
      with RNAP occur both with the -35 sequence and the TG extension, so that the
      sigma4 and sigma2 domains may simultaneously contact the promoter DNA. RNAP-DNA
      interactions were also detected immediately downstream of the -35 hexamer and in
      a more distal upstream segment, reflecting a wrapping of RNAP by the core and
      upstream promoter DNA. Altogether, the data reveal that promoter gapA P1 is a
      very efficient promoter sharing common properties with both extended -10 and non
      extended -10 promoters.

PMID- 15250825
TI  - DUK114, the Drosophila orthologue of bovine brain calpain activator protein, is a
      molecular chaperone.
AB  - UK114, the goat liver tumour antigen, is a member of a widely distributed family
      of conserved low-molecular-mass proteins (YER057c/YjgF/UK114), the function of
      which is ill understood. To the various orthologues diverse functions have been
      ascribed, such as translation inhibition, regulation of purine repressor or
      calpain activation. Owing to a limited sequence similarity to Hsp90 (heat-shock
      protein 90), they have also been proposed to be molecular chaperones; however,
      this has never been tested. In the present paper, we report the cloning and
      characterization of the Drosophila orthologue, DUK114. In brief, DUK114 had no
      effect that would have qualified it as a calpain activator. In contrast, it
      proved to be a very potent molecular chaperone in in vitro assays. In a heat
      aggregation test, it significantly decelerated the formation of citrate synthase
      aggregates. In a reverse assay, the recovery of the enzyme from urea- and heat
      induced denatured states was accelerated almost 3-fold. On a molar basis, the
      chaperone activity of the 15-kDa DUK114 is comparable with that of Hsp90, the
      almost 6-times-larger archetypal molecular chaperone. In similar assays, DUK114
      was ineffective with Drosophila calpain A or calpain B. To test for its chaperone
      activity in vivo, DUK114 was transfected into Schneider (S2) cells; after heat
      shock, the number of viable non-transfected cells started to increase after a lag
      time; in the presence of DUK114, cell proliferation started at once. Our work is
      the first experimental evidence that DUK114, and possibly other members of this
      family, are molecular chaperones.

PMID- 15250826
TI  - Reciprocal regulation of glutathione S-transferase spliceforms and the Drosophila
      c-Jun N-terminal kinase pathway components.
AB  - In mammalian systems, detoxification enzymes of the GST (glutathione S
      transferase) family regulate JNK (c-Jun N-terminal kinase) signal transduction by
      interaction with JNK itself or other proteins upstream in the JNK pathway. In the
      present study, we have studied GSTs and their interaction with components of the
      JNK pathway from Diptera. We have evaluated the effects of four Delta class
      Anopheles dirus GSTs, GSTD1-1, GSTD2-2, GSTD3-3 and GSTD4-4, on the activity of
      full-length recombinant Drosophila HEP (mitogen-activated protein kinase kinase
      7; where HEP stands for hemipterous) and the Drosophila JNK, as well as the
      reciprocal effect of these kinases on GST activity. Interestingly, even though
      these four GSTs are alternatively spliced products of the same gene and share
      >60% identity, they exerted different effects on JNK activity. GSTD1-1 inhibited
      JNK activity, whereas the other three GST isoforms activated JNK. GSTD2-2, GSTD3
      3 and GSTD4-4 were inhibited 50-80% by HEP or JNK but GSTD1-1 was not inhibited
      by JNK. However, there were some similarities in the actions of HEP and JNK on
      these GSTs. For example, binding constants for HEP or JNK inhibiting a GST were
      similar (20-70 nM). Furthermore, after incubation of the GSTs with JNK, both JNK
      and the GSTs changed catalytic properties. The substrate specificities of both
      GSTs and JNK were also altered after their co-incubation. In addition,
      glutathione modulated the effects of JNK on GST activity. These results emphasize
      that different GST spliceforms possess different properties, both in their
      catalytic function and in their regulation of signalling through the JNK pathway.

PMID- 15250827
TI  - Structural organization of mitochondrial human complex I: role of the ND4 and ND5
      mitochondria-encoded subunits and interaction with prohibitin.
AB  - Mitochondria-encoded ND (NADH dehydrogenase) subunits, as components of the
      hydrophobic part of complex I, are essential for NADH:ubiquinone oxidoreductase
      activity. Mutations or lack of expression of these subunits have significant
      pathogenic consequences in humans. However, the way these events affect complex I
      assembly is poorly documented. To understand the effects of particular mutations
      in ND subunits on complex I assembly, we studied four human cell lines: ND4 non
      expressing cells, ND5 non-expressing cells, and rho degrees cells that do not
      express any ND subunits, in comparison with normal complex I control cells. In
      control cells, all the seven analysed nuclear-encoded complex I subunits were
      found to be attached to the mitochondrial inner membrane, except for the 24 kDa
      subunit, which was nearly equally partitioned between the membranes and the
      matrix. Absence of a single ND subunit, or even all the seven ND subunits, caused
      no major changes in the nuclear-encoded complex I subunit content of
      mitochondria. However, in cells lacking ND4 or ND5, very low amounts of 24 kDa
      subunit were found associated with the membranes, whereas most of the other
      nuclear-encoded subunits remained attached. In contrast, membrane association of
      most of the nuclear subunits was significantly reduced in the absence of all
      seven ND proteins. Immunopurification detected several subcomplexes. One of
      these, containing the 23, 30 and 49 kDa subunits, also contained prohibitin. This
      is the first description of prohibitin interaction with complex I subunits and
      suggests that this protein might play a role in the assembly or degradation of
      mitochondrial complex I.

PMID- 15250828
TI  - Efficacy of mometasone furoate microemulsion in the treatment of erosive
      ulcerative oral lichen planus: pilot study.
AB  - BACKGROUND: Oral lichen planus (OLP) is a frequent immunological chronic disease,
      having different clinical forms: asymptomatic and symptomatic. Symptomatic OLP
      has been palliated with topical corticosteroids with different levels of efficacy
      and safety. The purpose of this pilot phase II clinical trial was to determine
      the efficacy of mometasone furoate microemulsion upon the symptoms and signs of
      erosive-ulcerative OLP. METHODS: Forty-nine patients with clinical and
      histologically confirmed erosive-ulcerative OLP were enrolled in this study (36
      women and 13 men). Their average age was 56.4 years (from 28 to 78). The
      treatment consisted of 0.1% mometasone furoate microemulsion mouthwash three
      times a day over 30 days. Pain, erythema and ulceration were assessed after 15
      and 30 days of treatment. The data was processed and statistically analysed by
      student's t-test for paired samples. RESULTS: Mometasone caused a statistically
      significant reduction in pain (3.58 vs. 0.65, P = 0.0000). Treatment
      significantly reduced the surface area of erythema (155.2 vs. 21.9 mm(2), P =
      0.0001) and ulceration (30.7 vs. 7.3 mm(2), P = 0.0000). None of these patients
      suffered severe adverse effects. CONCLUSIONS: Mometasone furoate microemulsion is
      a safe and effective therapy in the treatment of symptomatic erosive-ulcerative
      OLP.

PMID- 15250829
TI  - Elevated serum levels of the apoptosis related molecules TNF-alpha, Fas/Apo-1 and
      Bcl-2 in oral lichen planus.
AB  - BACKGROUND: The serum circulatory levels of apoptosis related molecules measured
      in patients with oral lichen planus (OLP) and healthy individuals in order to
      investigate possible alterations associated with the clinical forms of OLP.
      METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble Fas (sFas)
      and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in
      13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects.
      RESULTS: Significantly elevated levels of TNF-alpha and sFas detected in OLP
      patients as compared with controls. Serum concentrations of Bcl-2 although
      increased in 17/26 patients, they were not statistically significant. Reticular
      OLP exhibited slightly elevated TNF-alpha and significantly elevated Bcl-2 serum
      levels, compared with erosive OLP. CONCLUSIONS: These data suggest that a
      putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the
      OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive
      OLP may be associated with promotion of the disease activity.

PMID- 15250830
TI  - Regulation of keratinocyte growth factor and scatter factor in cyclosporin
      induced gingival overgrowth.
AB  - BACKGROUND: Epithelial proliferation is a histological characteristic of drug
      induced gingival overgrowth. Keratinocyte growth factor (KGF) and scatter factor
      (SF) are fibroblast-derived growth factors with potent mitogenic and motogenic
      effects on epithelial cells, and, therefore, could be involved in the
      pathogenesis of gingival overgrowth. The aims of this study were to investigate:
      (i) the effects of cyclosporin on KGF and SF expression by gingival fibroblasts;
      and (ii) the expression levels of KGF and SF mRNA in normal and overgrown
      gingival tissue. METHODS: The KGF and SF protein production was determined by
      enzyme-linked immunosorbent assay. Relative levels of KGF and SF mRNA expression
      were determined using semi-quantitative reverse transcriptase polymerase chain
      reaction. Expression levels in biopsies of normal and overgrown gum were also
      determined. RESULTS: In overgrown fibroblasts, 500 ng/ml cyclosporin
      significantly inhibited KGF and SF mRNA and protein while 2000 ng/ml cyclosporin
      induced a stimulatory effect. In normal cells cyclosporin significantly increased
      both KGF and SF. KGF and SF mRNA was detected in both normal and overgrown
      tissues with a tendency towards increased expression levels in overgrown tissue.
      CONCLUSION: These results suggest that KGF and SF may have an important role in
      cyclosporin-induced gingival overgrowth.

PMID- 15250831
TI  - Cytologic and DNA-cytometric very early diagnosis of oral cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of
      exfoliative cytology (EC) and DNA-image cytometry applied to suspicious oral
      lesions compared with synchronous histology. METHODS: Brush- and scalpel biopsies
      were obtained from 98 patients with suspicious oral lesions. In cases, in which
      EC revealed malignant or suspicious cells, nuclear DNA-contents were measured
      using a TV image analysis system. RESULTS: Among 98 oral lesions both cytological
      and histological diagnosis showed no sign of malignancy or dysplasia in 75. In 23
      cases cytology yielded tumor cell-positive (15), suspicious (four) or doubtful
      (four) results. DNA-cytometry showed aneuploidy in 19 of these. The comparison
      between cytological diagnosis combined with DNA-cytometry and biopsy-histology
      resulted in a sensitivity of 100% and a specificity of 97.4%. CONCLUSION: In
      conclusion, cytology with DNA-cytometry is a highly sensitive, specific and non
      invasive method for the early diagnosis of oral epithelial neoplasia, showing
      excellent compliance among patients.

PMID- 15250832
TI  - Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for
      oral carcinogenesis.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) can degrade extracellular matrix
      and basement membrane, and play an important role in the development and
      progression of multiple carcinomas, including oral squamous cell carcinoma
      (OSCC). A -1306C-->T polymorphism in the MMP-2 promoter disrupts Sp1-binding
      site, and results in reduction of transcriptional activity. This study aimed to
      assess the association of such genotype with the risk of OSCC and oral submucous
      fibrosis (OSF), which is a precancerous condition that exhibits excessive
      collagen production and etiologically links to areca use. METHODS: Genomic DNA
      from the blood samples of 121 OSCC cases, 58 OSF cases and 147 controls were
      amplified by polymerase chain reaction (PCR) and subjected to denaturing high
      performance liquid chromatography (dHPLC) analysis for genotyping. The OSCC were
      further classified into buccal squamous cell carcinoma (BSCC) and non-buccal
      squamous cell carcinoma (NBSCC), according to the site of involvement. Fisher's
      exact test and unconditional logistic regression models were used for statistical
      analysis. RESULTS: Subjects carrying CC genotype had nearly twofold increased
      risk for developing OSCC when comparing with CT or TT genotype. Subjects carrying
      CC genotype had more apparent risk (greater than fourfold) for developing NBSCC.
      However, no increase in risk for lymph node metastasis or advanced stage was
      identified in OSCC cases carrying such genotype. Preliminarily data suggest no
      significant association between subjects carrying CC genotype and the development
      of BSCC or OSF. CONCLUSION: This is the first paper demonstrating that functional
      genotype of MMP-2 promoter is a risk factor for oral carcinogenesis, particularly
      for the subsets occurring on non-buccal site.

PMID- 15250833
TI  - Salivary secretory leukocyte protease inhibitor increases in HIV infection.
AB  - BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is an antimicrobial
      protein found in saliva and having anti-HIV activity. The concentrations of SLPI
      in parotid and submandibular/sublingual (SMSL) saliva were determined in an
      HIV(+) population and compared with uninfected controls. The effect of highly
      active antiretroviral therapy (HAART) on the concentrations in saliva was
      determined. METHODS: Stimulated parotid and SMSL saliva was collected from 65
      HIV(+) patients and 19 healthy controls. Flow rates, total protein and SLPI
      concentrations were determined as well as the effect of HAART on these
      measurements. RESULTS: Mean flow rates were reduced for parotid (64%) and SMSL
      (44%) saliva of HIV(+) patients. Flow rate reductions were unaffected by HAART.
      Total protein concentration in HIV(+) parotid saliva was increased 56%; patients
      on HAART had higher concentrations than control. For both groups, SLPI
      concentrations of SMSL saliva were twice that of parotid saliva. For HIV(+)
      patients SLPI concentrations of both saliva types were 70% greater than control;
      the increase in parotid saliva was greater for those taking HAART. For each
      saliva type, the secretory rate and specific SLPI protein concentration were not
      different between the groups. Patients with low CD4(+) counts had greater SLPI
      concentrations in parotid saliva than control. There was a negative correlation
      between CD4(+) counts and the SLPI concentration of parotid saliva. CONCLUSIONS:
      Salivary flow rate is decreased and the concentration of SLPI is increased in the
      presence of HIV infection. SLPI concentration in parotid and SMSL saliva is
      greater with HAART.

PMID- 15250834
TI  - Immortalization of human dental papilla, dental pulp, periodontal ligament cells
      and gingival fibroblasts by telomerase reverse transcriptase.
AB  - BACKGROUND: Human telomerase reverse transcriptase (hTERT) is catalytic subunit
      of human telomerase. METHODS: We studied the immortalization of a series of human
      dental and periodontal cells by ectopic expression of hTERT and co-expression of
      hTERT with human papilloma virus 16 (HPV16) or simian virus 40 (SV40).
      Differentiation abilities of the established cell lines were studied in terms of
      the mineralized matrix formation and gene expression. RESULTS: We established
      immortalized gingival fibroblasts by hTERT, dental papilla and periodontal
      ligament cells by hTERT and HPV16, and pulp cells by hTERT and SV40. The papilla
      and pulp cells showed mineralization and dentin sialophosphoprotein (DSPP)
      expression when cultured in the presence of beta-glycerophosphate. The
      immortalized periodontal ligament cells did not show mineralization or DSPP
      expression, although expressions of alkaline phosphatase, osteopontin and
      osteocalcin were detected. CONCLUSIONS: These cell lines will be useful tools for
      studying the repair and regeneration of dental and periodontal tissues and
      various diseases including odontogenic tumors.

PMID- 15250836
TI  - Mitotic proliferation of myoepithelial cells during regeneration of atrophied rat
      submandibular glands after duct ligation.
AB  - BACKGROUND: The purpose of the present study was to elucidate whether
      myoepithelial cells proliferate mitotically during regeneration of rat
      submandibular glands after atrophy. METHODS: The excretory duct of the right
      submandibular gland of rats was doubly ligated near the hilum with metal clips,
      which were removed after 7 days of ligation (day 0). The regenerating right
      submandibular glands were removed from 0 to 14 days after removal of the clips.
      The removed tissue was examined with immunohistochemical double staining for
      proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells and
      actin as a marker of myoepithelial cells, as well as with transmission electron
      microscopy (TEM). RESULTS: The PCNA-positive myoepithelial cells were observed at
      the periphery of transitional duct-acinar structures, ducts and acini in the
      regenerating glands at every time-point, and the PCNA-labeling index of
      myoepithelial cells increased greatly especially between day 2 and 4. The mitosis
      of myoepithelial cell was also identified by TEM at day 4. CONCLUSION: These
      findings suggest that myoepithelial cells are able to proliferate mitotically
      during regeneration of rat submandibular gland.

PMID- 15250835
TI  - Histopathologic changes in dental and oral soft tissues in 2-butoxyethanol
      induced hemolysis and thrombosis in rats*.
AB  - BACKGROUND: 2-Butoxyethanol (2-BE; ethylene glycol monobutyl ether) is
      extensively used as a solvent in surface coatings, such as lacquers, enamels, and
      varnishes in industrial and household cleaning products. Its major toxicity is
      manifested in the circulation, as it induces hemolytic anemia and thrombosis in
      various organs. While 2-BE has been implicated in the induction of anemia in
      different species, the rat has proven most sensitive, especially the female of
      this species. The purpose of this study was to document the effects of 2-BE on
      dentition, the periodontal ligament, the tongue, the salivary glands, and the
      oral mucosa in male and female Fischer 344 rats. METHODS: The experiment included
      40 rats divided into five groups. Four groups were exposed to 2, 3, or 4 daily
      doses of 2-BE, and a fifth group served as control. The rats were killed on days
      2, 3, 4, and 29. The teeth and soft oral tissues were prepared for
      histopathologic observation. RESULTS: The histopathologic analysis showed that
      the major effect of 2-BE was exerted on the odontoblasts of the incisors and on
      molars, with greater effect on the incisors. Foci of damaged muscle cells in the
      tongue were also observed. The blood vessels were dilated and congested, and a
      primary thrombosis was seen in the dental pulp. CONCLUSIONS: The results of this
      study revealed a resemblance between the dental injuries in this rat model and
      those seen in sickle cell anemia in humans. This 2-BE animal model holds
      potential to assist in the discovery of preventive measures and/or treatment for
      dental injuries that occur in human diseases with hemolytic anemia.

PMID- 15250837
TI  - Maspin expression in normal and neoplastic salivary gland.
AB  - BACKGROUND: Maspin inhibits cell motility, invasion and metastasis. Loss or
      reduction in maspin expression has been associated with tumoral progression.
      METHODS: The presence of maspin was studied immunohistochemically in salivary
      gland tumours presenting cells with myoepithelial differentiation in their
      composition, and in normal salivary gland. RESULTS: Pleomorphic adenoma (PA)
      presented high expression of maspin, except in the spindle cells and occasional
      luminal cells. Epithelial-myoepithelial carcinoma and tubular adenoid cystic
      carcinoma (ACC) showed intense expression in all cells. Cribriform ACC evidenced
      only few positive cells of the luminal type, while solid subtype showed rare
      positive cells. Normal salivary gland tissue has shown low levels of maspin
      positivity. CONCLUSIONS: Maspin has small participation in normal salivary gland,
      is increased in PA, and decreases as the histological malignancy raises. Hence,
      in salivary gland, its expression is not exclusive of myoepithelial cells; thus,
      it should not be used as a marker for this cell. Nevertheless, we believe it is
      an important marker of biological behaviour in these tumours.

PMID- 15250838
TI  - Anorexia/bulimia-related sialadenosis of palatal minor salivary glands.
AB  - In patients affected by alimentary disorders sialadenosis is frequently observed.
      This non-inflammatory condition is described to affect major salivary glands,
      leading to the characteristic parotid and/or submandibular swelling. Thus fine
      needle aspiration cytology or parotid open biopsy are generally required to
      diagnose histologically the disorder. We report the case of a 28-year-old patient
      affected by bulimia/anorexia nervosa who presented, in addition to parotid
      enlargement, a bilateral symmetric painless soft swelling of the hard palate. The
      lesion was biopsied and histopathological examination showed the classical
      features of sialadenosis. To our knowledge, this is the first case of
      sialadenosis affecting palatal minor salivary glands. It underlines that when
      sialadenosis is clinically suspected, clinicians could check also patients' oral
      cavity for minor salivary glands involvement, in order to potentially avoid
      invasive extra-oral procedures and to easily confirm diagnosis with an intra-oral
      biopsy.

PMID- 15250839
TI  - Pacinian corpuscle in the juxtaoral organ of Chievitz.
AB  - The juxtaoral organ of Chievitz (JOOC) is a normal permanent anatomical structure
      located within the soft tissue overlying the angle of the mandible in the
      buccotemporal space. Although the sensory organ nature of JOOC, repeatedly
      mentioned in German publications, has been neglected in the last decade by the
      American anatomists and pathologists, we incidentally found JOOC-type squamous
      epithelium accompanied by Pacinian corpuscles. This fortuitous finding appears to
      be the first report of the authentic Paciniform nerve endings within JOOC,
      supporting its mechanosensory function.

PMID- 15250841
TI  - What interventions should we add to weight reducing diets in adults with obesity?
      A systematic review of randomized controlled trials of adding drug therapy,
      exercise, behaviour therapy or combinations of these interventions.
AB  - BACKGROUND: Evidence is needed for the effectiveness of interventions given with
      reducing diets for obese adults: drug therapy, exercise, or behaviour therapy.
      METHODS: We systematically reviewed randomized controlled trials in any language.
      We searched 13 databases and handsearched journals. Trials lasted 1 year or more.
      One investigator extracted data and a second checked data extraction. Trial
      quality was assessed. RESULTS: Adding orlistat to diet was associated with weight
      change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and
      statistically significant beneficial changes were found for total and LDL
      cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was
      associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg),
      and statistically significant beneficial effects on high density lipoprotein
      cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood
      pressure. Adding exercise to diet, or to diet and behaviour therapy, was
      associated with improved weight loss for up to 36 months and improvements in HDL,
      TGs and blood pressure. Adding behaviour therapy to diet, or to diet and
      sibutramine together, was associated with improved weight loss for up to 18
      months. Adding drugs, exercise or behaviour therapy to dietary advice was each
      associated with similar weight change. CONCLUSIONS: Adding orlistat, sibutramine,
      exercise, or behaviour modification to dietary advice can improve long-term
      weight loss.

PMID- 15250842
TI  - What are the long-term benefits of weight reducing diets in adults? A systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Evidence is needed for the best long-term diet for weight loss, and
      improvement in cardiac risk and disease in obese adults. METHODS: We
      systematically reviewed randomized controlled trials (RCTs) in any language. We
      searched 13 databases and handsearched journals. Trials lasted 1 year or more.
      One investigator extracted the data and a second checked data extraction. Trial
      quality was assessed. RESULTS: Low fat diets (LFDs) produced significant weight
      losses up to 36 months (-3.55 kg; 95% CI, -4.54 to -2.55 kg). Blood pressure,
      lipids and fasting plasma glucose improved with these diets after 12 months. Four
      studies found that LFDs may prevent type 2 diabetes and reduce antihypertensive
      medication for up to 3 years. A very low calorie diet (VLCD, < 4.2 MJ day(-1))
      was associated with the most weight loss after 12 months (-13.40 kg; 95% CI, 
      18.43 to -8.37 kg) in one small study with beneficial effects on asthma. There
      was no evidence that low carbohydrate protein sparing modified fasts (PSMFs) were
      associated with greater long-term weight loss than low calorie diets (LCDs, 4.2
      6.7 MJ day(-1)) or VLCDs. PSMFs were, however, associated with greater lowering
      of fasting plasma glucose and HbA1c than LCDs. CONCLUSIONS: Little evidence
      supports the use of diets other than LFDs for weight reduction. With the
      increasing prevalence of morbid obesity, long-term follow-up in RCTs is needed to
      evaluate the effect of LCDs, VLCDs and PSMFs more fully.

PMID- 15250843
TI  - Dietetic guidelines: diet in secondary prevention of cardiovascular disease
      (first update, June 2003).
AB  - AIM: To update dietetic guidelines summarizing the systematic review evidence on
      dietary advice to prevent further events in people with existing cardiovascular
      disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and
      EMBASE were comprehensively searched to November 2002 for systematic reviews on
      aspects of diet and heart health. Reviews were included if they searched
      systematically for randomised controlled trials relating to diet and secondary
      prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians
      Group critically appraised each review. The quality and results of each review
      were discussed and summarized in a meeting of the whole group. RESULTS: Providing
      evidence-based dietary information (including increasing omega-3 fat intake) to
      all people who have had a myocardial infarction will save more lives than
      concentrating dietary advice on just those in need of weight loss or lipid
      lowering. The practice of prioritizing dietetic time in secondary prevention to
      those with raised lipids is out of date since the advent of statin therapy.
      However, effective dietary advice for those with angina, stroke, peripheral
      vascular disease or heart failure is less clear. CONCLUSION: There is good
      systematic review evidence that dietary advice to those with coronary heart
      disease can reduce mortality and morbidity as well as modify some risk factors.
      Dietary advice that does this most effectively should be prioritized.

PMID- 15250844
TI  - The effect of practical portion size measurement aids on the accuracy of portion
      size estimates made by young adults.
AB  - A barrier to controlling the amount of food consumed may be the difficulty
      consumers have in accurately estimating portion sizes. Although portion size
      measurement aids (PSMAs) can improve estimation accuracy, their bulk and/or cost
      tends to make them impractical for regular use. The purpose of this study was to
      investigate the effect on portion size estimation accuracy of two practical
      PSMAs: a 2-D PSMA (life size picture of tennis and golf balls) and 3-D PSMAs
      (tennis and golf balls). Young adults were randomly assigned to one of two groups
      and estimated the portion sizes of 36 foods divided into three equal sets. PSMAs
      were not used to estimate portion sizes in Food Set 1. Study group 1 (n = 57)
      used the 2-D PSMA and study group 2 (n = 56) used the 3-D PSMAs to estimate the
      portion sizes in Food Set 2. Neither group used PSMAs to estimate portion sizes
      in Food Set 3. Repeated measures anova indicated that both groups significantly
      improved estimation accuracy between Food Sets 1 and 2 and between Foods Sets 1
      and 3. Thus, even short-term exposure to practical PSMAs may improve estimation
      accuracy and these improvements persist when the PSMA is no longer available.
      However, the accuracy rate for Food Set 2 was only about 60% indicating that a
      great deal of estimation error remains.

PMID- 15250845
TI  - Is dietary counselling effective in increasing dietary calcium, protein and
      energy intake in patients with osteoporotic fractures? A randomized controlled
      clinical trial.
AB  - To determine the feasibility of increasing the calcium, protein and calorie
      intake of osteoporotic fracture patients by repeated dietary counselling
      delivered by a dietitian, a randomized controlled trial was conducted. Among 189
      patients presenting with osteoporotic fractures to an Orthopaedics and
      Traumatology Department of a large regional hospital, 98 patients were randomized
      to the intervention group and 91 were randomized to the control group (with usual
      care). Intervention group received three sessions of dietary counselling with
      tailored made recommendations over a period of 4 months, while the control group
      only received dietary assessment and pamphlets on the prevention of osteoporosis.
      Almost all subjects in both intervention and control groups had calcium intake
      below the recommended level of 1000 mg at baseline. Half and 60% of subjects in
      both groups had total energy and protein intake below recommended levels
      respectively. The mean weights of control and intervention groups at baseline
      were 51.5 and 50.9 kg respectively, while the body mass index (BMI) were 22.6 (kg
      m(-2)) and 22.6 (kg m(-2)) respectively. After dietary intervention, significant
      increase of intake was seen in calcium intake (P = 0.0095 by t-test) in the
      intervention group. No significant increase was seen in protein or calorie
      intake. No significant change was observed in the body weight or BMI although
      there was a positive trend in the intervention group for all these parameters. We
      concluded that there was general malnutrition in Chinese elderly who presented
      with osteoporotic fractures. Dietary calcium could be increased by repeated
      professional dietary counselling. Future studies with longer duration and more
      objective clinical outcomes will be helpful to further demonstrate the long-term
      effects of dietary intervention on osteoporosis and other chronic diseases.

PMID- 15250846
TI  - Is fibre supplementation in paediatric sip feeds beneficial?
AB  - The usefulness of a paediatric fibre containing sip feeds specifically formulated
      for paediatrics has not been evaluated. In an open, prospective, parallel study
      the efficacy, safety and tolerance of a paediatric fibre-containing sip feed
      designed for children weighing 8-20 kg (1-6 years) was compared with a fibre-free
      sip feed in 60 children with chronic illness. The subjects either received a
      trial sip feed containing 150 kcal (100 ml)(-1) and 2.0 g (100 ml)(-1) of fibre
      or a fibre-free equivalent control sip feed for 12 weeks. Blood biochemistry,
      haematology, anthropometry, tolerance and food intake data were estimated during
      week 1 and 12. The fibre intake was higher (P < 0.0001) and laxative usage
      decreased in the fibre-containing sip feed group. The sip feed provided almost
      50% of fibre intake in the trial group. There were no differences in sip feed
      tolerance, anthropometry, nutritional biochemistry or haematology between the two
      groups. Sip feeds provide an important source of fibre for sick children with
      normal gut function requiring nutritional support.

PMID- 15250847
TI  - A critical evaluation of the relationship between serum vitamin B, folate and
      total homocysteine with cognitive impairment in the elderly.
AB  - BACKGROUND: Serum homocysteine increases with age and is also considered a marker
      for low serum vitamin B(12) and folate. Furthermore, raised serum total
      homocysteine has been associated with atrophic changes in the brain. An
      association between serum vitamin B(12)/folate and cognitive impairment would be
      of considerable public health importance in view of the increasing numbers of
      elderly people. AIM: To systematically review published studies on the
      relationship between serum vitamin B(12), folate and total homocysteine and
      cognitive function in the elderly. DESIGN AND DATA SOURCES: A systematic review
      was undertaken of published evidence in English, examining the association
      between low serum vitamin B(12)/folate and raised total homocysteine with
      cognitive impairment (as indicated by low scores on neuropsychological testing)
      in subjects aged over 60 years. Sixteen electronic databases and cited articles
      were searched. Of 383 potential articles, six fulfilled the eligibility criteria:
      three case control and three cohort studies were identified. 'The Cochrane Non
      Randomized Studies Methods Group' guidelines were used for assessment and
      extraction of data from these studies. RESULTS: All three case control studies
      found that serum total homocysteine was significantly higher in cases when
      compared with controls, and there was wide variation for both serum vitamin B(12)
      and folate in both groups of participants. The relationship of serum folate and
      vitamin B(12) status with cognitive impairment was heterogeneous and one case
      control study reported decreasing cognitive scores with increasing serum vitamin
      B(12). In the cohort studies, although serum total homocysteine could predict the
      rate of decline in neuropsychological testing, the overall odds ratio/relative
      risk (RR) of developing cognitive impairment in relation to levels of serum B(12)
      and serum folate were not significant. Although one study reported a significant
      RR of developing Alzheimer's disease when both serum folate and B(12) levels were
      low. One cohort study reported an increased prevalence of Alzheimer's type
      dementia in subjects who had normal serum vitamin B(12) at baseline. CONCLUSION:
      Serum total homocysteine is negatively correlated with neuropsychological tests
      scores. But the evidence does not support a correlation between serum vitamin
      B(12) or folate and cognitive impairment in people aged over 60 years. Hence,
      there is little evidence to justify treating cognitive impairment with vitamin
      B(12) or folate supplementation. This is consistent with the findings from recent
      systematic reviews of randomized double-blind trials, which have not found any
      evidence of potential benefit of vitamin supplementation. Further research is
      required in order to establish whether raised serum total homocysteine is a cause
      or consequence of disease.

PMID- 15250853
TI  - Relationship between heart rate turbulence and heart rate, heart rate
      variability, and number of ventricular premature beats in coronary patients.
AB  - INTRODUCTION: Heart rate variability (HRV) illustrates regulation of the heart by
      the autonomic nervous system whereas heart rate turbulence (HRT) is believed to
      reflect baroreflex sensitivity. The aim of this study was to determine the
      association between HRT and HRV parameters and the relationship between HRT
      parameters and heart rate and number of ventricular premature beats (VPBs) used
      to calculate HRT parameters. METHODS AND RESULTS: In 146 patients (117 males and
      29 females; mean age 62 years) with coronary artery disease, a 24-hour ECG Holter
      monitoring was performed to calculate mean heart rate (RR interval), number of
      VPBs, time- and frequency-domain HRV parameters and two HRT parameters:
      turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate
      regression analyses were performed to evaluate the association between tested
      parameters. Significant correlation between TS and mean RR interval was observed
      (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS
      values were significantly higher in patients with less than 10 VPBs/24 hours than
      in patients with more frequent VPBs. Significant associations between HRT and HRV
      parameters were found with TS showing stronger correlation with HRV parameters
      than TO (r value ranging from 0.35 to 0.62 for TS vs. -0.16 to -0.38 for TO).
      CONCLUSION: HRT parameters correlate strongly with HRV parameters indicating that
      HRT should be considered as a reflection of both baroreceptors response and
      overall autonomic tone. Heart rate dependence of turbulence slope indicates the
      need to adjust this parameter for heart rate.

PMID- 15250854
TI  - Automaticity in Mahaim fibers.
AB  - INTRODUCTION: Automatic rhythms associated with Mahaim fibers usually occur
      during radiofrequency catheter ablation. The incidence and significance of
      spontaneous automaticity in Mahaim fibers are unknown. METHODS AND RESULTS:
      Spontaneous automatic rhythms were observed in 5 (12.5%) of 40 patients with
      Mahaim fibers referred for nonpharmacologic therapy because of recurrent episodes
      of symptomatic tachyarrhythmias, usually antidromic circus movement tachycardia
      (33/40 patients). Three were female and two were male. Their mean age was 15 +/-
      7 years compared to 26 +/- 13 years of the patients without automaticity (P =
      0.09). Three patients had both antidromic tachycardia and asymptomatic
      spontaneous automatic rhythms recorded during ambulatory ECG (1 patient) or
      electrophysiologic study (2 patients). In 2 patients, the automatic rhythm
      triggered antidromic tachycardia. Two other patients had nonsustained repetitive
      episodes of wide QRS tachycardia due to automaticity arising in the Mahaim fiber,
      without antidromic tachycardia. All automatic rhythms were abolished by
      successful catheter ablation of the Mahaim fibers. CONCLUSION: Spontaneous
      automaticity occurred in 12.5% of our Mahaim patients and may trigger antidromic
      tachycardia. Spontaneous automaticity, which is not seen in rapidly conducting
      accessory pathways, is another argument for the presence of an AV nodal-like
      structure in Mahaim fibers.

PMID- 15250855
TI  - Electrophysiologic characteristics of atrial tachycardia originating from the
      right pulmonary veins or posterior right atrium: double potentials obtained from
      the posterior wall of the right atrium can be useful to predict foci of atrial
      tachycardia in right pulmonary veins or posterior right atrium.
AB  - INTRODUCTION: The right pulmonary veins (RPVs) and posterior wall of the right
      atrium (PRA) are anatomically located adjacent to each other. The aim of this
      study was to demonstrate the electrophysiologic characteristics of atrial
      tachycardia (AT) originating from the PRA or RPVs. METHODS AND RESULTS: A total
      of 26 consecutive patients with AT originating from the RPVs or PRA underwent
      detailed atrial endocardial mapping and successful radiofrequency catheter
      ablation. Eight foci were found in the PRA and 18 foci in the RPVs. Analysis of P
      wave configuration showed that lead V1 was the most helpful in distinguishing the
      AT foci between these two sites. In all cases, double potential (DP)
      configurations were recorded from several electrodes of a multielectrode catheter
      placed in the PRA, and the first DP component (FP) was the earliest potential
      recorded from the right atrium during the tachycardia. The amplitude of the FP
      was higher than that of the second DP component (SP) for AT foci originating in
      the PRA, whereas the reverse occurred for those in the RPV. The activation
      sequence of the FP was from superior to inferior for the AT foci in the superior
      RPV, whereas the reverse occurred for the AT foci in the inferior RPV.
      CONCLUSION: P wave configuration in lead V1 is helpful in distinguishing AT foci
      between those originating in the PRA and RPVs. The DPs obtained from the PRA can
      be useful in predicting whether AT foci originate from the PRA or RPVs.

PMID- 15250856
TI  - Restoration of heart rate turbulence by titrated beta-blocker therapy in patients
      with advanced congestive heart failure: positive correlation with enhanced vagal
      modulation of heart rate.
AB  - INTRODUCTION: Heart rate turbulence (HRT) is a powerful novel predictor for
      cardiovascular mortality. Chronic congestive heart failure is associated with
      abnormal HRT. Whether antiadrenergic beta-blocker therapy can restore control of
      HRT in patients with chronic congestive heart failure is unknown. METHODS AND
      RESULTS: A 24-hour Holter ECG recording was obtained before and 1 and 3 months
      after titrated addition of atenolol therapy in 10 consecutive patients with
      advanced congestive heart failure. Two parameters derived from HRT, turbulence
      slope (TS) and turbulence onset (TO), and time- and frequency-domain heart rate
      variability (HRV) parameters (SDNN, RMSSD, VLF, LF, HF) from 24-hour ECG were
      compared before and after beta-blocker therapy, together with the same parameters
      in age-matched normal control. Results showed that TS (3.1 +/- 2.2 vs 6.2 +/-
      3.0; P = 0.001) and all HRV parameters were increased after 3 months of atenolol
      treatment. No changes in TO were evident (0.6 +/- 0.5 vs -0.2 +/- 1.3; P = 0.13).
      The improvement of TS and the vagally mediated parameters of mean R-R interval,
      RMSSD, and the HF component of HRV were positively correlated. CONCLUSION:
      Abnormal HRT caused by chronic congestive heart failure can be restored by beta
      blocker therapy. The evolution of TS was positively correlated with measures of
      vagal modulation of heart rate.

PMID- 15250857
TI  - Improvement in heart rate turbulence as a measure of response to beta-blocker
      therapy for heart failure.

PMID- 15250858
TI  - Prospective assessment after pediatric cardiac ablation: demographics, medical
      profiles, and initial outcomes.
AB  - INTRODUCTION: A multicenter prospective study was designed and implemented to
      assess the short- and longer-term results and risks associated with
      radiofrequency (RF) ablation in children. METHODS AND RESULTS: Patients recruited
      for the study were aged 0 to 16 years with supraventricular tachycardia due to
      accessory pathways or AV nodal reentrant tachycardia (AVNRT), excluding patients
      with nontrivial congenital heart disease. A national registry also was
      established, and contributing centers were encouraged to enroll all pediatric
      patients, aged 0 to 21 years, undergoing ablation at their center. This report
      summarizes acute results of these procedures. For analysis, subjects were divided
      into three groups: the prospective cohort (n = 481), cohort-eligible registry
      participants (n = 504), and not cohort eligible registry participants (n =
      1,776). Prospectively enrolled cohort patients were similar to cohort-eligible
      patients in terms of demographic and other patient characteristics. Overall
      success rates for RF ablation were high (95.7%), with higher success rates for
      left-sided and particularly left free-wall pathways (97.8%) than right free-wall
      pathways (90.8%). Complications of both electrophysiologic study and RF ablation
      were infrequent (4.2% and 4.0%, respectively), and there were no deaths. AV block
      was uncommon overall (1.2%) and was limited to ablation in AVNRT (2.1%) and
      septal accessory pathways (3.0%). CONCLUSION: Despite the multicenter and
      prospective design, the study demonstrates high success rates and low
      complication rates, which are comparable to prior single-center retrospective
      studies. These results may serve as the current best benchmark for expected
      results in the pediatric population, aged 0 to 16 years, both in terms of acute
      success rates and the occurrence of complications.

PMID- 15250859
TI  - Quality improvement in pediatric radiofrequency ablation.

PMID- 15250860
TI  - Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias.
AB  - INTRODUCTION: In patients with permanent pacemakers, mode switching events often
      are interpreted as surrogate markers for atrial tachyarrhythmias. The aim of this
      study was to determine the accuracy of automatic mode switching algorithms in
      patients with permanent pacemakers for the diagnosis of atrial tachyarrhythmias.
      METHODS AND RESULTS: Forty patients with tachycardia-bradycardia syndrome and
      Medtronic Thera or Kappa 700 permanent pacemakers underwent Holter monitoring.
      Date, time of onset, and duration of each mode switch episode as recorded by the
      pacemaker and each atrial tachyarrhythmia episode as recorded by the Holter
      monitor were compared. Sixteen patients had a total of 54 atrial tachyarrhythmias
      documented on Holter monitoring (47 atrial fibrillation, 7 atrial flutter).
      Comparison of Holter data with pacemaker interrogation demonstrated that 53
      (98.1%) of 54 atrial tachyarrhythmia episodes resulted in mode switching with one
      13-second episode of mode switching during sinus rhythm. The sensitivity and
      specificity of mode switching for the duration of atrial tachyarrhythmias were
      98.1% and 100%, respectively. The algorithms detected 98.9% of the total duration
      of atrial fibrillation and 96.4% of the total duration of atrial flutter.
      CONCLUSION: In patients with tachycardia-bradycardia syndrome and permanent
      pacemakers having these mode switching algorithms, mode switching events are
      reliable surrogate markers for atrial tachyarrhythmias. Therefore, mode switching
      may serve as a valuable tool for clinical decision making and further research
      into the natural history and burden of atrial tachyarrhythmias.

PMID- 15250861
TI  - Atrial tachyarrhythmias detected by automatic mode switching: quo vadis?

PMID- 15250862
TI  - Azygos vein lead implantation: a novel adjunctive technique for implantable
      cardioverter defibrillator placement.
AB  - High defibrillation thresholds (DFTs) occasionally are encountered during
      placement of implantable cardioverter defibrillators (ICDs). There are multiple
      strategies to lower DFTs in such patients, including reassessment of right
      ventricular lead position, alteration of the shock waveform, and implantation of
      subcutaneous arrays. This article describes a novel technique of implanting a
      high-voltage lead in the azygos vein. This procedure may serve as an adjunctive
      approach to reduce DFTs. The anatomic location of the azygos vein posterior to
      the heart provides a suitable shocking vector between the right ventricular
      electrode, a high-voltage lead placed in the azygos vein, and the ICD can.

PMID- 15250863
TI  - Pulmonary vein isolation for atrial fibrillation in patients with symptomatic
      sinus bradycardia or pauses.
AB  - INTRODUCTION: Sick sinus syndrome is commonly associated with tachyarrhythmias
      and bradyarrhythmias that often are symptomatic. The aim of this study was to
      assess the effect of pulmonary vein isolation in patients with sick sinus
      syndrome and atrial fibrillation (AF). METHODS AND RESULTS: Three hundred
      fourteen consecutive patients who underwent pulmonary vein isolation between
      December 2000 and January 2002 were included in the study. Thirty-one patients
      had sick sinus syndrome, which was defined as a preprocedural history of
      symptomatic sinus bradycardia or pauses. Endpoints included AF recurrence, change
      in the frequency of sinus pauses, and symptoms of presyncope or syncope, as well
      as mean heart rate and percentage of atrial pacing in patients with pacemakers
      implanted prior to the pulmonary vein isolation. Patients had AF for an average
      of 6 +/- 3 years. Patients were 58 +/-8 years old and had ejection fractions of
      55 +/- 4%. Sixty-one percent had implanted pacemakers. AF recurred within 6
      months in 4 patients. Two had a successful second pulmonary vein isolation
      procedure. There were no recurrences of presyncopal events (P < 0.05) or
      documented sinus pauses (P < 0.05) after successful pulmonary vein isolation in
      the patients without permanent pacemakers. Patients with pacemakers had a 13-fold
      reduction in the percentage of atrial pacing (P < 0.05). Both groups showed a
      significant increase in average heart rates at 6-month follow-up. CONCLUSION:
      Cure of AF by pulmonary vein isolation helped resolve the clinical manifestations
      of sick sinus syndrome, suggesting that the occurrence of AF and/or the
      associated treatment could be partially responsible for sick sinus syndrome.

PMID- 15250864
TI  - Optimization of atrial defibrillation with a dual-coil, active pectoral lead
      system.
AB  - INTRODUCTION: Atrial defibrillation can be achieved with standard implantable
      cardioverter defibrillator (ICD) leads, but the optimal shocking configuration is
      unknown. The objective of this prospective study was to compare atrial
      defibrillation thresholds (DFTs) with three shocking configurations that are
      available with standard ICD leads. METHODS AND RESULTS: This study was a
      prospective, randomized, paired comparison of shocking configurations on atrial
      DFTs in 58 patients. The lead system evaluated was a transvenous defibrillation
      lead with coils in the superior vena cava (SVC) and right ventricular apex (RV)
      and a left pectoral pulse generator emulator (Can). In the first 33 patients,
      atrial DFT was measured with the ventricular triad (RV --> SVC + Can) and
      unipolar (RV --> Can) shocking pathways. In the next 25 patients, atrial DFT was
      measured with the ventricular triad and the proximal triad (SVC --> RV + Can)
      configurations. Delivered energy at DFT was significantly lower with the
      ventricular triad compared to the unipolar configuration (4.7 +/- 3.7 J vs 10.1
      +/- 9.5 J, P < 0.001). Peak voltage and shock impedance also were significantly
      reduced (P < 0.001). There was no significant difference in DFT energy when the
      ventricular triad and proximal triad shocking configurations were compared (3.6
      +/- 3.0 J vs 3.4 +/- 2.9 J for ventricular and proximal triad, respectively, P =
      NS). Although shock impedance was reduced by 13% with the proximal triad (P <
      0.001), this effect was offset by an increased current requirement (10%).
      CONCLUSION: The ventricular triad is equivalent or superior to other possible
      shocking pathways for atrial defibrillation afforded by a dual-coil, active
      pectoral lead system. Because the ventricular triad is also the most efficacious
      shocking pathway for ventricular defibrillation, this pathway should be preferred
      for combined atrial and ventricular defibrillators.

PMID- 15250865
TI  - Transmural action potential repolarization heterogeneity develops postnatally in
      the rabbit.
AB  - INTRODUCTION: In the hereditary long QT syndrome, arrhythmia risk changes with
      age despite the presence of an ion channel mutation throughout development. Age
      dependent changes in the transmural dispersion of repolarization may modulate
      this vulnerability. We recorded cardiac action potentials in infant,
      periadolescent, and adult rabbit myocardium to determine if transmural
      heterogeneities in repolarization are developmentally determined. METHODS AND
      RESULTS: Arterially perfused ventricular preparations were studied from 2-week (n
      = 7), 7-week (n = 7), and adult (n = 6) NZW rabbits. Action potentials were
      recorded with microelectrodes in five regions: epicardium (epi), subepicardium
      (subepi), midwall (mid), subendocardium (subendo), and endocardium (endo) during
      endocardial S1 pacing at cycle lengths of 2,000, 1,000, and 500 ms. At 2 weeks,
      the transmural APD90 profile was flat. With age, APD prolongation from subepi to
      endo created a transmural repolarization gradient. At 7 weeks, APD90 was
      significantly longer at subendo [204 +/- 2 ms (mean +/- SE) 2,000-ms cycle
      length, P < 0.05] vs both endo (193 +/- 2 ms) and epi (172 +/- 2 ms), causing a
      heterogeneous transmural APD90 gradient. In adults, the transmural gradient was a
      smooth continuum such that APD was shortest in epicardium and longest in
      endocardium. CONCLUSION: The transmural distribution of APD is developmentally
      determined. Tissue-specific age-dependent changes in APD can result in transmural
      repolarization heterogeneity. These age-related effects may modulate arrhythmia
      vulnerability during development.

PMID- 15250866
TI  - Effect of rapid biphasic shock subpulse switching on ventricular defibrillation
      thresholds.
AB  - INTRODUCTION: The aim of this study was to demonstrate that significant
      reductions in defibrillation threshold (DFT) can be achieved by rapidly switching
      defibrillation pulses within an overall biphasic envelope between multiple
      endovascular electrode sets. METHODS AND RESULTS: Defibrillation electrodes were
      implanted in four locations in nine anesthetized swine (41.7 +/- 8.7 kg).
      Electrodes were implanted into the right ventricular apex (RV), the superior vena
      cava (SVC), over the left pectoral region as a "hot can" (Can), and within the
      middle cardiac vein on the posterior left ventricular (LV) surface. The 50% DFT
      (level for which 50% of delivered shocks successfully defibrillated) for control
      shocks (7-ms first phase, 0.5-ms interpulse period, 4-ms second phase, RV- -->
      SVC+ + Can+) were determined to have energy of 20.5 +/- 5.5 J (mean +/- SD). Mean
      50% DFTs were also determined for waveforms that split each phase of the same
      overall biphasic waveform between various electrode sets. Each phase was divided
      into 2, 3, 4, or 6 subpulses, the defibrillation shock was sequentially delivered
      to multiple electrode sets, and DFTs were determined (11.9 +/- 4.8 J, 11.7 +/-
      2.9 J, 17.9 +/- 8.7 J, 16.7 +/- 6.1 J, respectively). DFT energy was
      statistically lower than the control (Wilcoxon sign rank test; P < 0.05) when
      each phase was divided into 2 or 3 subpulses. CONCLUSION: Rapid shock switching
      within an overall biphasic waveform between electrode sets including an electrode
      in the middle cardiac vein potentially can lower DFT energy by 40% or more.

PMID- 15250867
TI  - Left atrial isthmus: anatomic aspects relevant for linear catheter ablation
      procedures in humans.
AB  - INTRODUCTION: The success rate of catheter maze ablation procedures for atrial
      fibrillation depends upon adequate electrical isolation by performing linear
      ablation lesions. However, recurrence of atrial arrhythmias is not uncommon,
      particularly in the so-called left atrial isthmus, between the orifice of the
      left inferior pulmonary vein and the mitral valve annulus. The focus of the
      present study is the anatomy of this area. METHODS AND RESULTS: Twenty human
      hearts were studied. The distance between the left inferior pulmonary vein and
      the mitral valve, the thickness of the left atrial myocardium, and the extent of
      left atrial myocardium toward the mitral valve were measured. The AV groove
      contained a fat pad harboring the great cardiac vein. The distance between the
      vein and the valve varied considerably (range 17-51 mm). The great cardiac vein
      coursed along the inferior left atrial wall, approximately 1 cm above the level
      of the mitral valve. Myocardial thickness also varied considerably (distal: range
      1.4-7.7 mm, midway: range 1.2-4.4 mm, proximal: range 0-3.2 mm). Left atrial
      myocardium extended onto the mitral valve in two hearts, and the left atrial
      myocardium ended above the level of the mitral valve (range 1.8-5.1 mm) in six
      hearts. An important variable because it raises the question of how much energy
      should be used--and at which point--to achieve an adequate transmural ablation
      line. CONCLUSION: The great cardiac vein is not an adequate marker for the level
      of the mitral valve, left atrial myocardium may continue onto the mitral valve,
      the distance between the left inferior pulmonary vein and mitral valve varies
      considerably, and left atrial myocardial thickness is highly variable and not
      uniform.

PMID- 15250868
TI  - The left atrial isthmus: from dissection bench to ablation lab.

PMID- 15250869
TI  - Electrophysiologic effects of nicorandil on the guinea pig long QT1 syndrome
      model.
AB  - INTRODUCTION: The slow component of the delayed rectifier K+ current IKs
      modulates repolarization of the cardiac action potential (AP), and the loss of
      IKs is known to cause long QT1 (LQT1) syndrome by prolonging action potential
      duration (APD). In this study, we generated a guinea pig LQT1 syndrome model
      using the IKs blocker chromanol 293B and then assayed the electrophysiologic
      effects of the ATP-sensitive potassium channel IK,ATP opener nicorandil on this
      model. METHODS AND RESULTS: Transmembrane action potentials of perfused right
      ventricular papillary muscle preparations and both in vitro and in vivo ECGs of
      guinea pigs were recorded. Blockade of IKs by chromanol 293B (30 microM)
      prolonged the action potential duration at 90% repolarization (APD90) by 8.5% and
      QT interval by 16.5% of control values. In addition, proarrhythmic early
      afterdepolarizations (EADs) and ventricular fibrillation were observed.
      Venoinjection of chromanol 293B (1 mg/kg) revealed 10.9% QT prolongation.
      Nicorandil (5-30 microM) dose-dependently shortened APD90 under the control
      condition, whereas it reversed the AP prolongation effect of chromanol 293B by
      7.4% at the 30 microM concentration. Moreover, nicorandil shortened QT intervals
      both in vitro and in vivo and displayed an inhibitory effect on EADs and
      ventricular fibrillation. CONCLUSION: The ATP-sensitive potassium channel opener
      nicorandil may be an effective drug in the therapy of LQT1 syndrome by shortening
      APD and the QT interval.

PMID- 15250870
TI  - Use of potassium channel openers for pharmacologic modulation of cardiac
      excitability.

PMID- 15250871
TI  - Reentry in a pulmonary vein as a possible mechanism of focal atrial fibrillation.
AB  - The case of an 18-year-old woman with recurrent idiopathic catecholamine
      sensitive paroxysmal atrial fibrillation is reported. Recordings of multiple
      initiations of atrial fibrillation at the proximal part of the right superior
      pulmonary vein suggested local reentry in the vein as the mechanism of atrial
      fibrillation. A single radiofrequency pulse delivered at this site resulted in
      definite cure of the arrhythmia.

PMID- 15250872
TI  - Histopathologic background for resistance to conventional catheter ablation of
      common atrial flutter.
AB  - Histopathologic examination of the cavotricuspid isthmus in which a large-tip
      catheter was necessary to achieve conduction block is presented. No thickened
      myocardium or prominent trabeculation was observed on the ablation line. A small
      cardiac vein extending through the isthmus across the ablation scar was detected.
      The remaining myocardial cells were distributed along the small cardiac vein. It
      is possible that the luminal blood flow of the small cardiac vein protects the
      surrounding atrial muscle from effective delivery of radiofrequency energy.

PMID- 15250873
TI  - Bigeminal rhythm: what is the mechanism?

PMID- 15250874
TI  - Supraventricular tachycardia observed upon termination of atrial flutter: what is
      the mechanism?

PMID- 15250875
TI  - Short coupled premature ventricular contraction initiating ventricular
      fibrillation in a patient with Brugada syndrome.

PMID- 15250876
TI  - Cryoablation of focal atrial tachycardia originating close to the
      atrioventricular node.

PMID- 15250877
TI  - Evolution of mapping and anatomic imaging of cardiac arrhythmias.

PMID- 15250878
TI  - Looking at big brothers for clues.

PMID- 15250879
TI  - Diversity and ecology of soil fungal communities: increased understanding through
      the application of molecular techniques.
AB  - Fungi fulfil a range of important ecological functions, yet current understanding
      of fungal biodiversity in soil is limited. Direct DNA extraction from soil,
      coupled with polymerase chain reaction amplification and community profiling
      techniques, has proved successful in investigations of bacterial ecology and
      shows great promise for elucidating the taxonomic and functional characteristics
      of soil fungal communities. These community profiling techniques include
      denaturing gradient gel electrophoresis (DGGE), temperature gradient gel
      electrophoresis (TGGE), single-strand conformation polymorphism (SSCP), terminal
      restriction fragment length polymorphism (T-RFLP), amplified rDNA restriction
      analysis (ARDRA), amplified ribosomal intergenic spacer analysis (ARISA) and
      cloning, and are generally coupled with DNA sequencing. The techniques and their
      potential limitations are discussed, along with recent advances that have been
      made possible through their application in soil fungal ecology. It is unlikely
      that a single approach will be universally applicable for assessing fungal
      diversity in all soils or circumstances. However, judicious selection of the
      methodology, keeping the experimental aims in mind, and the exploitation of
      emerging technologies will undoubtedly increase our understanding of soil fungal
      communities in the future.

PMID- 15250880
TI  - Analysis and glycosyl composition of the exopolysaccharide isolated from the floc
      forming wastewater bacterium Thauera sp. MZ1T.
AB  - Conditions were developed for the reproducible production, isolation and
      characterization of a novel microbial extracellular polysaccharide believed to be
      involved in transient viscous bulking at an industrial wastewater treatment
      plant. The exopolysaccharide was extracted from cell-free culture supernatants of
      Thauera sp. strain MZ1T grown on a minimal medium with succinate. The purified
      polymer was found to be approximately 260 kDa in size by gel-permeation
      chromatography. The GC-MS analysis of the alditol acetate and per-O
      trimethylsilyl methyl glycoside derivatives revealed that the exopolysaccharide
      was composed of four monosaccharides including: rhamnose, galacturonic acid, N
      acetylglucosamine and N-acetylfucosamine. Glucose, which also appeared at low
      levels, is most likely from a co-eluting glucan. The FTIR and NMR spectroscopic
      analyses further revealed the presence of esterified component groups on the
      polymer. These results represent the first published description of a
      polysaccharide from a member of the genus Thauera, and lay the foundation for a
      deeper understanding of the factors potentially involved in zoogloeal cluster
      formation and viscous bulking.

PMID- 15250881
TI  - Temporary cyst formation in phytoplankton: a response to allelopathic
      competitors?
AB  - Competition among phytoplankton for limiting resources may involve direct or
      indirect interactions. A direct interaction of competitors is the release of
      chemicals that inhibit other species, a process known as allelopathy. Here, we
      investigated the allelopathic effect of three toxic microalgae species
      (Alexandrium tamarense, Karenia mikimotoi and Chrysochromulina polylepis) on a
      natural population of the dinoflagellate Scrippsiella trochoidea. Our major
      findings were that in addition to causing death of S. trochoidea cells, the
      allelopathic species also induced the formation of temporary cysts in S.
      trochoidea. Because cysts were not lysed, encystment may act as a defence
      mechanism for S. trochoidea to resist allelochemicals, especially when the
      allelopathic effect is moderate. By forming temporary cysts, S. trochoidea may be
      able to overcome the effect of allelochemicals, and thereby have an adaptive
      advantage over other organisms unable to do so.

PMID- 15250882
TI  - Bacterial diversity in marine hydrocarbon seep sediments.
AB  - Marine seeps introduce significant amounts of hydrocarbons into oceans and create
      unusual habitats for microfauna and -flora. In the vicinity of chronic seeps,
      microbes likely exert control on carbon quality entering the marine food chain
      and, in turn, hydrocarbons could influence microbial community composition and
      diversity. To determine the effects of seep oil on marine sediment bacterial
      communities, we collected sediment piston cores within an active marine
      hydrocarbon seep zone in the Coal Oil Point Seep Field, at a depth of 22 m in the
      Santa Barbara Channel, California. Cores were taken adjacent to an active seep
      vent in a hydrocarbon volcano, on the edge of the volcano, and at the periphery
      of the area of active seepage. Bacterial community profiles were determined by
      terminal restriction fragment length polymorphisms (TRFLPs) of 16S ribosomal
      genes that were polymerase chain reaction (PCR)-amplified with eubacterial
      primers. Sediment carbon content and C/N ratio increased with oil content.
      Terminal restriction fragment length polymorphisms suggested that bacterial
      communities varied both with depth into sediments and with oil concentration.
      Whereas the apparent abundance of several peaks correlated positively with
      hydrocarbon content, overall bacterial diversity and richness decreased with
      increasing sediment hydrocarbon content. Sequence analysis of a clone library
      generated from sediments collected at the periphery of the seep suggested that
      oil-sensitive species belong to the gamma Proteobacteria and Holophaga groups.
      These sequences were closely related to sequences previously recovered from
      uncontaminated marine sediments. Our results suggest that seep hydrocarbons exert
      a strong selective pressure on bacterial communities in marine sediments. This
      selective pressure could, in turn, control the effects of oil on other biota in
      the vicinity of marine hydrocarbon seeps.

PMID- 15250883
TI  - Diversity of the archaeal community in 44 anaerobic digesters as determined by
      single strand conformation polymorphism analysis and 16S rDNA sequencing.
AB  - The diversity of Archaea in anaerobic digesters was characterized by strand
      conformation polymorphism (SSCP) analysis and the sequencing of 16S rDNA genes.
      The 44 digesters sampled, located in eight different countries, treated effluents
      from agriculture, the food processing and petro-chemical industries, pulp and
      paper plant, breweries, slaughterhouses and municipal waste. All the existing
      processes were represented among the samples (fixed-film, fluidized bed, stirred
      tank, UASB, sequential batch reactor, lagoon). Single strand conformation
      polymorphism analysis targeting the V3 region of 16S rDNA revealed between four
      to six distinct archaeal peaks per digester. The diversity of dominant Archaea in
      the 44 digesters was estimated as 23 different 16S rDNA sequences. Cloning of
      archaeal 16S rRNA genes from 11 distinct total genomic DNA, screening of clones
      by SSCP and the sequencing of 170 of them made it possible to characterize these
      SSCP peaks. All the sequences retrieved were members of the Euryarchaeaota
      subdomain. Furthermore, most of the sequences retrieved were very close to
      already known and cultivated strains or to environmental clones. The most
      frequent archaeal sequences were close to Methanosaeta concilii and to a 16S rDNA
      clone vadinDC06 located in the Methanobacterium clade (84% and 73% of digesters
      respectively). The other sequences were members of the Methanobacteriales and the
      Methanomicrobiales families. Only one sequence was far from any sequence of the
      database and it could be grouped with several sequences of environmental clones.
      Each digester harboured between two to nine archaeal sequences with only one of
      them corresponding to a putative acetate-utilizing species. Furthermore, the
      process in the digesters appeared to play a part in the distribution of archaeal
      diversity.

PMID- 15250884
TI  - Molecular detection and isolation of facultatively methylotrophic bacteria,
      including Methylobacterium podarium sp. nov., from the human foot microflora.
AB  - This is the first study to demonstrate that diverse methylotrophic bacteria occur
      in the human foot microflora. Polymerase chain reaction (PCR) amplification of
      DNA from the soles and toe clefts of feet of five subjects indicated
      Methylobacterium strains to be present in all cases. Polymerase chain reaction
      amplification also showed the gene for the alpha-subunit of methanol
      dehydrogenase (mxaF) to be present in all samples. Two types of mxaF were
      recovered, one closest to that of Methylobacterium extorquens and the other most
      similar to that of Hyphomicrobium methylovorum. Numerous methylotrophic strains
      able to grow on methylamine were isolated with ease from the feet of nine
      volunteers. These were found by 16S rRNA analysis to be most closely related to
      Methylobacterium species, Brevibacterium casei, Pseudomonas strain NZ099 and P.
      migulae. Three strains from two subjects were of a novel species,
      Methylobacterium podarium sp. nov. This facultatively methylotrophic, obligately
      aerobic, pink-pigmented, non-motile rod grew with a wide range of multicarbon and
      one-carbon compounds including citrate, xylose, mono-, di-, and trimethylamine,
      dimethylsulphide, methanethiol, dimethylsulphoxide, dimethylsulphone and
      methanol.

PMID- 15250885
TI  - Abundance of active and inactive microcystin genotypes in populations of the
      toxic cyanobacterium Planktothrix spp.
AB  - To investigate the abundance of active and inactive microcystin genotypes in
      populations of the filamentous cyanobacterium Planktothrix spp., individual
      filaments were grown as clonal strains in the laboratory and analysed for
      microcystin synthetase (mcy) genes and microcystin. Twenty-three green-pigmented
      strains of P. agardhii originating mostly from shallow water bodies fell into two
      groups, those possessing mcyA and those lacking mcyA. In contrast, all of the 49
      strains that were assigned to the red-pigmented P. rubescens contained mcyA. One
      strain of P. agardhii and eight strains of P. rubescens contained the total
      microcystin synthetase gene cluster but were found inactive in microcystin
      synthesis. To investigate the natural abundance of inactive mcy genotypes in P.
      rubescens individual filaments sampled from Lake Irrsee and Lake Mondsee
      (Austria) were analysed directly for the presence of mcyA and microcystin by
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. All
      filaments assigned to P. rubescens contained mcyA. The proportion of inactive
      microcystin genotypes in populations with a low (Irrsee) or high density
      (Mondsee) of P. rubescens was 5% and 21%, each. The results of this study
      demonstrate that P. rubescens typically contain mcy genes whereas P. agardhii
      have a patchy distribution of mcy genes. In both species microcystin producers co
      occur with non-microcystin producers due to the absence/inactivation of mcy
      genes.

PMID- 15250886
TI  - From PCBs to highly toxic metabolites by the biphenyl pathway.
AB  - The degradation of polychlorobiphenyls (PCBs) by diverse bacteria, including
      Burkholderia sp. LB400, is incomplete with a concomitant accumulation of
      metabolic intermediates. In this study, the toxicity of diverse (chloro)biphenyls
      and of their biotransformation into the first two metabolic intermediates of the
      biphenyl pathway, were determined for the model bacterium Escherichia coli.
      Recombinant E. coli strains expressing different subsets of bph genes of strain
      LB400 accumulated metabolic intermediates from (chloro)biphenyls. During
      biotransformation of these compounds into metabolic intermediates, the viability
      and metabolic kinetics were determined. The toxicity of biotransformation of
      (chloro)biphenyls into different metabolic intermediates of (chloro)biphenyls
      varied. Dihydrodiols and dihydroxybiphenyls are very toxic metabolites for
      bacteria even after short incubation times, affecting the cell viability much
      more than (chloro)biphenyls. When bacteria transformed 2-CB into dihydrodiol or
      dihydroxybiphenyl, a great decrease of intact cells and abundant cell lysis was
      observed by transmission electronic microscopy. Cell viability of Burkholderia
      sp. LB400 and of E. coli exposed directly to 2,3-dihydroxybiphenyl decreased also
      drastically. The toxicity of metabolites generated during oxidation of PCBs may
      partly explain the recalcitrance to biodegradation of these pollutants.
      Conversion of less toxic compounds into products with increased toxicity
      resembles the bioactivation of xenobiotics in higher organisms.

PMID- 15250887
TI  - Mechanism of chromate reduction by the Escherichia coli protein, NfsA, and the
      role of different chromate reductases in minimizing oxidative stress during
      chromate reduction.
AB  - Chromate [Cr(VI)] is a serious environmental pollutant, which is amenable to
      bacterial bioremediation. NfsA, the major oxygen-insensitive nitroreductase of
      Escherichia coli, is a flavoprotein that is able to reduce chromate to less
      soluble and less toxic Cr(III). We show that this process involves single
      electron transfer, giving rise to a flavin semiquinone form of NfsA and Cr(V) as
      intermediates, which redox cycle, generating more reactive oxygen species (ROS)
      than a divalent chromate reducer, YieF. However, NfsA generates less ROS than a
      known one-electron chromate reducer, lipoyl dehydrogenase (LpDH), suggesting that
      NfsA employs a mixture of uni- and di-valent electron transfer steps. The
      presence of YieF, ChrR (another chromate reductase we previously characterized),
      or NfsA in an LpDH-catalysed chromate reduction reaction decreased ROS generation
      by c. 65, 40, or 20%, respectively, suggesting that these enzymes can pre-empt
      ROS generation by LpDH. We previously showed that ChrR protects Pseudomonas
      putida against chromate toxicity; here we show that NfsA or YieF overproduction
      can also increase the tolerance of E. coli to this compound.

PMID- 15250888
TI  - Differential response of archaeal and bacterial communities to nitrogen inputs
      and pH changes in upland pasture rhizosphere soil.
AB  - Grassland management regimens influence the structure of archaeal communities in
      upland pasture soils, which appear to be dominated by as yet uncultivated non
      thermophilic Crenarchaeota. In an attempt to determine which grassland management
      factors select for particular crenarchaeal community structures, soil microcosm
      experiments were performed examining the effect of increased pH, application of
      inorganic fertilizer (ammonium nitrate) and sheep urine deposition on both
      archaeal and bacterial communities in unmanaged grassland soil. As grassland
      management typically increases pH, a further experiment examined the effect of a
      reduction in pH, to that typical of unimproved grassland soils, on archaeal and
      bacterial communities. The RT-PCR amplification of 16S rRNA followed by
      denaturing gradient gel electrophoresis analysis demonstrated a distinct and
      reproducible effect on bacterial communities after incubation for 28 or 30 days.
      In contrast, none of the treatments had a significant effect on the structure of
      the crenarchaeal community, indicating that these factors are not major drivers
      of crenarchaeal community structures in grassland soils.

PMID- 15250889
TI  - Salmonella diversity associated with wild reptiles and amphibians in Spain.
AB  - During the spring and summer of 2001, faeces from 166 wild reptiles (94
      individuals) and amphibians (72 individuals) from 21 different species found in
      central Spain were examined for the presence of Salmonella. Thirty-nine reptiles
      (41.5%) yielded 48 Salmonella isolates, whereas all the amphibians examined were
      negative. Subspecies Salmonella enterica enterica (I) accounted for up to 50% of
      isolates. Fourteen isolates (29.2%) belonged to subspecies diarizonae (IIIb), six
      isolates (12.5%) to subspecies salamae (II), and four isolates (8.3%) to
      subspecies arizonae (IIIa). Twenty-seven different serotypes were identified.
      Serotypes Anatum (12.5%), Herzliya (8.3%), Abony, 18:l,v:z, 9,12:z29:1,5 and
      38:z10:z53 (6.2%/each) were the most frequently isolated. A high percentage
      (39.6%) of isolates belonged to serotypes previously associated with
      environmental sources. Also, 37.5% of isolates belonged to serotypes which had
      been related to human cases of salmonellosis. From these data, it is concluded
      that wild reptiles, but apparently not amphibians, may represent an important
      reservoir of Salmonella in nature and have potential implications for public
      health.

PMID- 15250891
TI  - Psychiatric morbidity in psoriasis: a review.
AB  - Psoriasis is a common condition, affecting 1.5-2% of the population of
      industrialized countries. It is important for clinicians to be aware that
      psoriasis can have a substantial emotional impact on an individual, which is not
      necessarily related to the extent of skin disease. This review examines current
      literature addressing the psychological and emotional aspects of psoriasis. A
      literature search of the MEDLINE (1966-2002) and PsycINFO (1984-2002) computer
      databases and bibliographies was carried out. Papers selected for the review
      included English language reviews and all original research relevant to the
      topic, in the form of randomized controlled trials, cohort studies, case-control
      studies, cross-over and uncontrolled clinical trials, patient surveys, quality-of
      life studies, case series and case reports. Despite significant shortcomings, the
      available prevalence studies showed uniformly high rates of psychopathology among
      psoriasis sufferers. The few intervention studies available are summarized and
      critically discussed. Psoriasis is associated with a variety of psychological
      problems, including poor self esteem, sexual dysfunction, anxiety, depression and
      suicidal ideation. The clinical severity of the psoriasis may not reflect the
      degree of emotional impact of the disease. A number of psychological
      interventions have shown promise in recent trials. It is important that
      clinicians consider the psychosocial aspects of this illness.

PMID- 15250893
TI  - Role of adjuvant radiotherapy in recurrent earlobe keloids.
AB  - Earlobe keloids are commonly encountered in dermatological practice and often
      prove to be recurrent, despite a variety of treatment options. Recurrent keloids,
      particularly in the head and neck, are associated with unsightly cosmetic
      consequences, particularly in younger patients. There is no consensus regarding
      the optimal treatment for recurrent keloids. However, re-excision accompanied by
      adjuvant treatment is often recommended. Low-dose fractionated radiotherapy (12
      Gy in three fractions) delivered within 24 hours of excision remains an effective
      adjuvant option, although due consideration needs to be given to the small risk
      of radiation-induced malignancy. We aim to discuss the role of adjuvant
      radiotherapy for recurrent keloids and present the relevant literature.

PMID- 15250894
TI  - Guttate psoriasis following Ecstasy ingestion.
AB  - A 23-year-old man presented with the onset of a widespread pruritic eruption 4
      days after ingestion of an Ecstasy tablet for the first time. The rash was
      characterized by small papules up to 10 mm in diameter distributed in a guttate
      pattern over most of his body and displaying the Kobner phenomena. Histology
      diagnosed a psoriasiform drug eruption. The eruption was not responsive to the
      initial treatment of topical betamethasone dipropionate 0.1% ointment and oral
      prednisolone. Prompt resolution was achieved with narrowband UVB treatment and
      avoidance of rechallenge.

PMID- 15250895
TI  - Scarring of the eyelids from Coblation treatment.
AB  - Coblation therapy has been recently proposed as a new bipolar electrosurgical
      method for facial resurfacing. Initial reports suggested this therapy to be very
      safe with a minimal amount of training required. To date there have be no reports
      of scarring with its use. Scarring of the lower eyelids is reported in a 50-year
      old woman who underwent Coblation to improve the skin texture and fine lines of
      her lower eyelids. It is concluded that Coblation can cause scarring.

PMID- 15250896
TI  - Photodynamic therapy for subungual Bowen's disease.
AB  - A 35-year-old police shooting instructor with a 4-year history of Bowen's disease
      of the nail bed on his right index finger confirmed histologically, was
      successfully treated with photodynamic therapy (PDT). Four cycles of PDT were
      used with two different photosensitizers: 20% 5-amino-levulinic acid oil in water
      emulsion and methyl amino-levulinate (Metvix) cream. The lesion was successfully
      treated with clinical and histological clearance. There was minimal loss of time
      from work, with neither functional nor cosmetic deficits.

PMID- 15250897
TI  - Atrophic dermatofibrosarcoma protuberans: an uncommon and misleading variant.
AB  - A 23-year-old man presented with an atrophic lesion on his left anterior shoulder
      that had been present for at least 10 years. A previous biopsy had suggested a
      fibrohistiocytic origin; however, clinically it resembled morphoea or
      atrophoderma, and the lesion was observed. Fifteen months later, the lesion was
      noted to have grown slightly. A repeat biopsy showed dermatofibrosarcoma
      protuberans, with a storiform spindle cell proliferation with positive CD34
      staining. The lesion was excised with a 3-cm margin. Awareness of this rare
      presentation may assist in earlier diagnosis.

PMID- 15250898
TI  - Multiple eccrine hidrocystomas.
AB  - The clinical and pathological features and treatment of two patients with
      multiple eccrine hidrocystomas are presented. The first case is characterized by
      multiple pearly papules with a bluish hue located in the periorbital region and
      the bridge of the nose. The second case is characterized by multiple, skin
      coloured papules located in the periorbital area, forehead, chin and nose. Both
      were exacerbated by a hot and humid environment. Histopathologically, both
      demonstrated a unilocular cyst located in the dermis, with a 2-3-layer wall
      composed of cuboidal epithelium that was non-keratinizing. Treatment with topical
      atropine sulphate 1% in aqueous solution three times a day was instituted in the
      first case; however, this was poorly tolerated because of blurred vision and
      nausea. The lesions were subsequently hyfrecated with a good response. The second
      case was treated with topical atropine sulphate 1% in aqueous solution three
      times a day with a good response.

PMID- 15250899
TI  - Idiopathic granulomatous vulvitis.
AB  - A 20-year-old woman initially presented with clinical evidence of an acute vulval
      inflammatory disorder incorrectly diagnosed as a Bartholin's abscess. Prolonged
      healing associated with infection followed attempts to incise and biopsy the
      area. Over a decade the condition has followed a chronic course with
      exacerbations and remissions and the vulva has become progressively more swollen
      and distorted. Lymphangiomas have developed. Histology showed non-necrotizing
      granulomas. Investigations for Crohn's disease and sarcoidosis were negative.
      Prednisone resulted in improvement during acute inflammatory episodes.

PMID- 15250900
TI  - Molluscum contagiosum in atopic dermatitis treated with 0.1% tacrolimus ointment.
AB  - A case of molluscum contagiosum arising on the face and neck of a woman using
      topical tacrolimus over a period of 6 weeks for the treatment of atopic
      dermatitis is presented. Of particular note, these lesions remained confined to
      areas treated with tacrolimus and did not extend to adjacent regions treated with
      topical corticosteroids.

PMID- 15250901
TI  - Weathering of hair in trichoteiromania.
AB  - A 74-year-old woman presented with an 18-month history of broken vertex scalp
      hairs as a consequence of chronic rubbing. Light microscopy of the 1-2 cm hairs
      demonstrated distal brush-like splitting. Education and behavioural therapy were
      instituted. After 4 months of reduced rubbing of the vertex scalp hairs, the
      hairs re-grew with no evidence of persistent hair shaft abnormality.

PMID- 15250902
TI  - Follicular mycosis fungoides mimicking a cutaneous B-cell lymphoproliferative
      disorder.
AB  - Follicular mycosis fungoides (MF) is an uncommon histological variant of MF
      characterized by infiltrates of atypical lymphocytes around and within the
      epithelium of the hair follicles (folliculotropism). Here we report a patient
      with rapidly progressive follicular MF on the face, associated with concurrent
      typical MF lesions elsewhere. The histology was unusual, as apart from dense
      lymphoid infiltrates showing folliculotropism and epidermotropism, there was a
      prominent B-cell component with germinal centres, leading to an initial diagnosis
      of cutaneous B-cell lymphoma. The final diagnosis of follicular MF was
      established on demonstration of clonal T-cell receptor gene arrangements and lack
      of clonality for heavy chain gene rearrangements. This case illustrates a variant
      of MF that has a more rapid progression than the otherwise indolent course of
      classical MF over many years, and the diagnostic pitfalls, whereby the histology
      can mimic a B-cell proliferative disorder.

PMID- 15250903
TI  - Allergic contact dermatitis to methylprednisolone aceponate in a topical
      corticosteroid.
AB  - A 42-year-old registered nurse presented with a recurrent history of
      multifactorial hand dermatitis, which had ceased to respond to the topical
      corticosteroid that she was using. Patch testing revealed strong reactions to
      both Advantan Fatty Ointment (Commonwealth Serum Laboratories, Melbourne,
      Australia), and its active ingredient, methylprednisolone aceponate.
      Methylprednisolone aceponate is one of the more sensitizing topical
      corticosteroids and is becoming increasingly recognized as a significant
      allergen.

PMID- 15250904
TI  - Use of infliximab in the treatment of psoriasis.

PMID- 15250905
TI  - Acral dysesthesia and trastuzumab (Herceptin).

PMID- 15250912
TI  - Blood pressure measurement in hemodialysis patients.
AB  - Measurement of blood pressure (BP) poses some unique challenges in hemodialysis
      patients. Timing of BP measurement in relation to dialysis, changes in
      interdialytic weight gain, and inconsistent BP measurement technique in dialysis
      units contribute to the variability of BP readings in this population. This may
      contribute to the equivocal relationship between hypertension and cardiovascular
      outcomes documented in several epidemiologic studies in this population. Home BP
      readings are promising, but need to be validated as a measure of the burden of
      hypertension in this population. It is important to standardize BP measurement in
      all hemodialysis units according to published guidelines to improve the
      management of hypertension. Future research studies should carefully validate the
      technique used to measure BP.

PMID- 15250913
TI  - Ambulatory blood pressure monitoring in hemodialysis patients: a critique and
      literature review.
AB  - Ambulatory blood pressure (ABP) monitoring has been in use for nearly four
      decades. In that time, the advantages of using a more reproducible and accurate
      method to assess the true contribution of blood pressure to the cardiovascular
      risk profile of patients have steadily become more clearly established, balanced
      by the additional expense and expertise involved. In nephrology, and in
      particular in dialysis patients, there are significant difficulties in accurately
      registering truly representative blood pressure values and understanding the
      relationship between blood pressure, end-organ damage, and patient mortality.
      This arises because of the way in which hemodialysis acutely changes blood
      pressure values as well as the widespread abnormality of diurnal blood pressure
      rhythm seen in dialysis patients. Use of ABP monitoring can go some way to
      overcoming these obstacles. In this review we critically examine the use of ABP
      monitoring in the understanding of blood pressure control in dialysis patients.

PMID- 15250914
TI  - Role of sodium and volume in the pathogenesis of hypertension in hemodialysis.
AB  - Hypertension is a common finding in chronic hemodialysis (HD) patients.
      Cardiovascular (CV) disease is the leading cause of death in this population, and
      hypertension is a significant risk factor for CV events. Understanding the
      etiology of hypertension in chronic HD patients is critical in order to optimize
      treatment and reduce the morbidity and mortality associated with hypertension.
      Although the pathogenesis of hypertension in HD patients is multifactorial, two
      of the major risk factors are increased extracellular volume and sodium intake.
      Control of extracellular volume has been shown to normalize blood pressure (BP),
      but this normalization lags behind the extracellular volume contraction ("lag
      phenomenon"). A sodium load leads to an increase in BP by causing an increase in
      extracellular volume, resulting in a transient increase in cardiac output and an
      increase in total peripheral resistance. Sodium may be implicated in the
      hypertension of end-stage renal disease (ESRD) patients through hypervolemia
      independent mechanisms. Aggressive control of extracellular volume and dietary
      sodium intake can normalize BP in chronic HD patients and reduce the morbidity
      associated with hypertension-related CV disease.

PMID- 15250915
TI  - Volume-independent mechanisms of hypertension in hemodialysis patients: clinical
      implications.
AB  - The renin-angiotensin and sympathetic nervous systems are often activated in
      hemodialysis (HD) patients; the pathogenesis of this condition is discussed.
      Medications aimed at reducing renin and sympathetic activity may improve the
      cardiovascular prognosis, independent of its effect on blood pressure. This
      knowledge has important implications for the choice of treatment in HD patients.

PMID- 15250916
TI  - Hypertension and survival in hemodialysis patients.
AB  - Hypertension is clearly an independent risk factor for cardiovascular (CV) events
      and death in the general population, but the relationship between blood pressure
      (BP) and survival in dialysis patients is less clear. In dialysis populations at
      lower risk of CV events, BP is directly related to survival, while in those with
      high risk, it has been difficult to show such an effect. The effects of cardiac
      disease complicate the relationship between BP and outcome. Retrospective studies
      of large cohorts, with high prevalence of CV disease, have shown a U-shaped
      relationship between both systolic and diastolic BP and outcome. These findings
      probably reflect a high prevalence of cardiac failure and thus high mortality
      associated with low BP (i.e., a so-called reverse causation). Pulse pressure
      (high systolic BP and low diastolic BP) predicts outcome in hypertensive dialysis
      patients. Whether this reflects advanced vessel wall disease or is an independent
      etiologically significant risk factor is unclear. However, the current
      uncertainties as to the exact relationship between BP and outcome in dialysis
      patients do not warrant complacency regarding the prevention and treatment of
      hypertension.

PMID- 15250917
TI  - Cardiac disease in chronic uremia: can it explain the reverse epidemiology of
      hypertension and survival in dialysis patients?
AB  - Definitive randomized trials are rare in the dialysis literature. Treatment
      decisions are often based on extrapolation from trials in other populations and
      observational studies in dialysis patients. "Reverse epidemiology" is a term
      increasingly applied to classic cardiovascular risk factors in studies of
      dialysis patients. The term is used when outcome associations are the opposite of
      those seen in general population studies. Hypertension is an archetypal example,
      with several studies showing inverse associations with mortality. As a term,
      "reverse epidemiology" is intellectually unsatisfactory because validation of the
      real direction of an association is only possible with experimental designs. In
      contrast, blood pressure (BP) is associated with typical association patterns for
      outcomes other than death, including left ventricular hypertrophy and cardiac
      failure, which are dominant entities in dialysis populations. There is a strong
      suspicion that current analytical approaches may partly explain the paradox. For
      example, it is possible that unmeasured comorbidities are associated with lower
      BP levels. In addition, few studies use BP as a time-integrated parameter, which
      is problematic given the variability of this parameter. Several recent studies
      suggest that using pulse pressure as a BP parameter may normalize associations
      with mortality. BP, extracellular blood volume, residual renal function, and
      vasoactive medications are interlinked. Time-integrated analysis that examines
      all these parameters concurrently makes sense, but has rarely been attempted. A
      large burden of cardiac disease and insensitive analytical approaches may go a
      long way toward explaining the reverse epidemiology of hypertension and survival
      in dialysis patients.

PMID- 15250918
TI  - Dialysate composition and hemodialysis hypertension.
AB  - Dialysis prescriptions have evolved to take advantage of new technology and serve
      a burgeoning patient population. High-sodium bicarbonate-based dialysate was
      first formulated in 1982 to enable short, safe, comfortable, high-efficiency
      hemodialysis (HD). Near-universal adaptation of these high-sodium formulas has
      virtually eliminated profound dialysis disequilibrium and greatly reduced
      dialysis discomfort, but has created a syndrome of dialysis salt loading with
      accentuated postdialysis thirst, interdialytic weight gain, and hypertension.
      Available technology will soon permit individuals to receive isonatremic dialysis
      with dialysate customized to the patient's serum sodium activity. Then, rather
      than choosing between comfortable, safe, high-efficiency dialysis with salt
      loading; cramps, asthenia, and symptomatic hypotension using low-sodium, high
      efficiency rapid HD to control blood pressure (BP) and weight gain; or
      comfortable, slow, low-efficiency HD with BP control, physicians may be able to
      minimize symptoms and avoid dialysis salt loading while providing maximum time
      for rehabilitative activities. The current use of a single sodium activity for
      all patients ignores the inter- and intraindividual variability in serum sodium
      activity in our patients. This results in undesired consequences for 20-40% of
      patients. The application of even more severe salt loading through high-salt
      sodium modeling only accentuates the long-term problems of excessive thirst,
      weight gain, and hypertension.

PMID- 15250919
TI  - Dietary sodium restriction for hypertension in dialysis patients.
AB  - A close relationship between sodium and hypertension exists and this relationship
      is even more pronounced in renal failure and dialysis patients. Hypertension is
      one of the strongest predictors of poor outcome in dialysis patients. Almost all
      end-stage renal disease (ESRD) patients have hypertension and positive sodium
      balance, resulting in extracellular volume (ECV) expansion-the most important
      contributing factor to hypertension. Thus the effective management of
      hypertension requires normalization of the sodium balance and ECV. Two important
      methods to achieve this are limiting interdialytic weight gain (IDWG) and a
      dialysis process that is able to remove all IDWG and consistently attain dry
      weight. Since IDWG is directly dependent on sodium intake and the resulting
      thirst, sodium restriction is the most effective way to limit IDWG.
      Ultrafiltration and dialysate sodium concentration influence sodium removal, ECV
      control, and blood pressure (BP) control. Thus the dialysis session should be
      long enough to achieve dry weight and frequent enough to maintain appropriate BP.

PMID- 15250920
TI  - Drug therapy for hypertension in hemodialysis patients.
AB  - The majority of end-stage renal disease (ESRD) patients are hypertensive. Drug
      therapy for hypertension in hemodialysis (HD) patients includes all classes of
      antihypertensive drugs, with the sole exception of diuretics. Angiotensin
      converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may
      decrease morbidity and mortality by reducing the mean arterial pressure (MAP),
      aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as
      left ventricular hypertrophy (LVH) and probably reduction of C-reactive protein
      (CRP) and oxidant stress. Potential risk factors include hyperkalemia,
      anaphylactoid reaction with AN69 membranes (particularly ACE inhibitors), and
      aggravation of renal anemia. beta-blockers decrease not only mortality, blood
      pressure (BP), and ventricular arrhythmias, but also improve left ventricular
      function in ESRD patients. Nonselective beta-blockers can cause an increase in
      serum potassium (particularly during fasting or exercise). Lisinopril and
      atenolol have a predominant renal excretion and therefore a prolonged half life
      in ESRD patients. Thus thrice-weekly supervised administration of these drugs
      after HD can enhance BP control. The use of calcium channel blockers is also
      associated with lower total and cardiovascular-specific mortality in HD patients.
      Minoxidil is a very potent vasodilator that is generally reserved for dialysis
      patients with severe hypertension. Hypertensive dialysis patients who are
      noncompliant with their medications may benefit from transdermal clonidine
      therapy once a week. The majority of dialysis patients need a combination of
      several antihypertensive drugs for adequate BP control.

PMID- 15250921
TI  - Hypertension control with daily dialysis.
AB  - Hypertension is present in 60-90% of patients on maintenance hemodialysis (HD)
      and it is an important cause of cardiovascular (CV) mortality and morbidity.
      Frequent and prolonged HD has been uniformly shown to control hypertension in end
      stage renal disease (ESRD) patients more effectively than conventional HD. The
      etiology of hypertension is predominantly volume dependent, but in a subset of
      patients increased renin, sympathetic overactivity, and endothelial dysfunction
      may play a role. Intradialytic hypotension precludes attainment of dry weight and
      hence optimal control of hypertension in conventional HD is challenging. Frequent
      and prolonged dialysis with gentle and persistent ultrafiltration allows time for
      refilling of the intravascular compartment and permits normalization of
      extracellular volume. It is also possible that intensive dialysis enables removal
      of pressor molecules and improves endothelial function. Improved blood pressure
      control translates into regression of left ventricular hypertrophy in patients on
      daily HD. Thus prolonged and frequent dialysis permits better control of
      hypertension via volume and volume-independent mechanisms and also improves
      cardiac geometry.

PMID- 15250922
TI  - Cardiac consequences of hypertension in hemodialysis patients.
AB  - Hypertension in end-stage renal disease (ESRD) is an important risk factor for
      left ventricular hypertrophy (LVH), cardiac failure, coronary artery disease
      (CAD), and arrhythmia. LVH is generally considered an integrator of the long-term
      effects of hypertension and other cardiovascular (CV) risk factors and represents
      the strongest predictor of adverse CV outcomes in ESRD patients. The risk of
      heart failure is higher in patients with a history of hypertensive renal disease
      than in those with other diagnoses. Both coronary heart disease (CHD) and LVH
      predict congestive heart failure, which is often the ultimate cause of death in
      patients with cardiac ischemia or LVH. A history of long-standing hypertension is
      associated with ischemic heart disease both in cross-sectional and prospective
      studies in ESRD. Atrial fibrillation and ventricular arrhythmias are highly
      prevalent in dialysis patients and are implicated in mortality and sudden death
      in this population. Despite the lack of evidence from randomized controlled
      trials, it appears reasonable that interventions aimed at curbing the high CV
      mortality of ESRD should be targeted to both hypertension and LVH.

PMID- 15250923
TI  - Noncardiac consequences of hypertension in hemodialysis patients.
AB  - The incidence of cerebrovascular events and peripheral vascular disease is higher
      in dialysis patients compared to the general population. Although normotensive
      dialysis patients have an elevated risk of stroke, hypertension remains an
      important risk factor for symptomatic cerebrovascular accidents. The risk of
      stroke increases in a linear fashion with blood pressure (BP) level. Furthermore,
      hypertension is also an important risk factor for silent cerebral infarction in
      dialysis patients. With regard to peripheral vascular disease, the association
      with hypertension is less clear. The spectrum of cerebrovascular accidents
      differs from the general population, as the relative incidence of cerebral
      hemorrhage to cerebral infarction is much higher. The prognosis of cerebral
      hemorrhage is poor and depends on the size and location of the hemorrhage. In
      order to prevent noncardiac complications, strict control of hypertension is of
      major importance in dialysis patients.

PMID- 15250924
TI  - An alternative approach to the central circulation from above the diaphragm.
AB  - This is a review of a new fluoroscopically guided safe technique to place
      tunneled cuffed hemodialysis (HD) catheters via the supraclavicular location.
      Right supraclavicular catheters were placed in 12 patients who had no patent
      internal jugular veins. The placements were all successful and without serious
      complications. Over the 2 years of follow-up, two episodes of thrombosis/stenosis
      (16.7%) resulted in catheter removal. The rate of infection was 8%, or one
      episode in 1204 patient-days. The average length of use was 111 days. The average
      rate of blood flow was 354 cc/min. The right supraclavicular approach for
      tunneled HD catheters is safe and compares favorably to the internal jugular
      approach for patients with limited access options.

PMID- 15250925
TI  - National surveillance of dialysis-associated diseases in the United States, 2001.
AB  - In December 2001, all U.S. chronic hemodialysis (HD) centers were surveyed
      regarding selected patient care practices and dialysis-associated diseases. The
      results were compared with similar surveys conducted in previous years. During
      1997-2001, the percentage of patients vaccinated against hepatitis B virus (HBV)
      infection increased from 47% to 60% and the percentage of staff vaccinated
      increased from 87% to 89%. In 2001, an estimated 65% of patients had been
      vaccinated for influenza and 26% for pneumococcal pneumonia. In 2001, routine
      testing for antibody to hepatitis C virus (anti-HCV) was performed on staff at
      42% of centers and on patients at 62% of centers; anti-HCV was found in 1.5% of
      staff and 8.6% of patients. In 2001, the incidence of HBV infection was higher
      among patients in centers where injectable medications were prepared at the
      dialysis station, and both HCV prevalence and incidence were higher among
      patients in centers where injectable medications were prepared at the dialysis
      station compared to a dedicated medication room. During 1995-2001, the percentage
      of patients who received dialysis through central catheters increased from 13% to
      25%; this trend is worrisome, as infections and antimicrobial use are higher
      among patients receiving dialysis through catheters. However, during the same
      period, the percentage of patients receiving dialysis through fistulas increased
      from 22% to 30%. In 2001, 25% of catheters were used for new patients awaiting an
      arteriovenous (AV) access, 28% for established patients with a failed access
      awaiting new AV access, 40% as an access of last resort, and 6% for other
      reasons, including patient preference. The percentage of centers reporting one or
      more patients infected or colonized with vancomycin-resistant enterococcus (VRE)
      increased from 12% in 1995 to 31% in 2001.

PMID- 15250926
TI  - Nephrology education clinic for early chronic kidney disease.

PMID- 15250929
TI  - Nocturnal home hemodialysis.

PMID- 15250933
TI  - The transcription network regulating melanocyte development and melanoma.
AB  - The enormous variety of pigmentation phenotypes in nature reflects a series of
      remarkable events that begin in the neural crest and end with the manufacture and
      distribution of pigment by mature melanocytes located in the epidermis and hair
      follicles. While the origins of melanoblasts from multipotent precursors in the
      neural crest is striking in itself, yet more so is the fact that these pioneer
      melanoblasts manage to undertake and survive their long migration, and in doing
      so proliferate and maintain their identity before ultimately arriving at their
      destination and undergoing differentiation. With the application of the powerful
      combination of genetics and molecular and cell biology the mystery surrounding
      the genesis of the melanocyte lineage is slowly being unravelled. At its heart is
      the powerful alliance between signal transduction and transcription that
      coordinates the program of gene expression that confers on a cell its identity,
      provides its passport for migration, and instructs it in the arts of survival and
      timely reproduction. The realization that the proliferation and migration of
      melanoblasts during development resembles closely the proliferation and
      metastasis of melanoma, a highly dangerous and increasingly common cancer, serves
      to highlight the value of the melanocyte system as a model for addressing key
      issues of general significance in both development and cancer.

PMID- 15250934
TI  - Genetics and evolution of pigment patterns in fish.
AB  - Vertebrate pigment patterns are both beautiful and fascinating. In mammals and
      birds, pigment patterns are likely to reflect the spatial regulation of
      melanocyte physiology, via alteration of the colour-type of the melanin
      synthesized. In fish, however, pigment patterns predominantly result from
      positioning of differently coloured chromatophores. Theoretically, pigment cell
      patterning might result from long-range patterning mechanisms, from local
      environmental cues, or from interactions between neighbouring chromatophores.
      Recent studies in two fish genetic model systems have made progress in
      understanding pigment pattern formation. In embryos, the limited evidence to date
      implicates local cues and chromatophore interactions in pigment patterning. In
      adults, de novo generation of chromatophores and cell-cell interactions between
      chromatophore types play critical roles in generating striped patterns;
      orientation of the stripes may well depend upon environmental cues mediated by
      underlying tissues. Further genetic screens, coupled with the routine
      characterization of critical gene products, promises a quantitative understanding
      of how striped patterns are generated in the zebrafish system. Initial 'evo-devo'
      studies indicate how fish pigment patterns may evolve and will become more
      complete as the developmental genetics is integrated with theoretical modelling.

PMID- 15250935
TI  - Pheomelanin coat colour dilution in French cattle breeds is not correlated with
      the TYR, TYRP1 and DCT transcription levels.
AB  - In this study we report the isolation of full-length cDNAs and the expression
      patterns of TYR, TYRP1 and DCT in four e/e cattle breeds exhibiting different
      pheomelanic coat colours ranging from reddish brown to creamy white phenotypes.
      Predicted proteins encoded by bovine TYR, TYRP1 and DCT display high levels of
      homology and contain all characteristic domains shared between their mouse and
      human counterparts. The full expression of these three genes is observed in
      melanocytes of black areas of E(D)/E(D) Prim'Holstein's animals. On the other
      hand, e/e melanocytes of animals belonging to the Blonde d'Aquitaine (blond),
      Limousine (red) and Salers (reddish brown) breeds present different levels of
      down-regulated TYR and DCT expression and a complete repression of TYRP1.
      Surprisingly, e/e melanocytes of animals belonging to the Charolais breed (creamy
      white) present an inverse relationship between TYR, TYRP1 and DCT expression and
      its lower melanogenic activity. The sum of these results shows that the dilution
      of the coat colour in French cattle breeds is not correlated with a transcription
      level of TYR family genes. Other possible modifier loci are suggested.

PMID- 15250936
TI  - Pterin-dependent tyrosine hydroxylase mRNA is not expressed in human melanocytes
      or melanoma cells.
AB  - Pterin-dependent tyrosine hydroxylase has been described to occur occasionally in
      melanocytes. It is therefore important to quantify the mRNA of this enzyme in
      pigment cells to understand whether this enzyme can take an active part in
      pigment formation. A real-time reverse transcription-polymerase chain reaction
      method was used to quantify tyrosine hydroxylase mRNA in melanocytes and melanoma
      cells. The calibrator was obtained by amplification of a segment of cDNA from
      tyrosine hydroxylase mRNA, which included the target thus allowing enumeration of
      the number of transcripts per cell. In melanocytes (n = 3), tyrosine hydroxylase
      mRNA ranged from non-detectable to 0.000492 transcripts/cell and in melanoma
      cells from non-detectable to 0.005340 transcripts/cell. In neuroblastoma cells,
      the median tyrosine hydroxylase mRNA number was 0.4 transcripts/cell (range 0.02
      25 transcripts/cell). The amount of tyrosine hydroxylase mRNA in the pigment
      cells was far less than the mRNA concentrations of four melanocyte-specific
      proteins measured in the same melanocytes and melanoma cells. We conclude that on
      the average less than 1 of 1000 melanocytes and melanoma cells contains at least
      one tyrosine hydroxylase mRNA molecule. Consequently, in 999 of 1000 cells
      translation into the corresponding enzyme protein cannot occur because of the
      lack of an mRNA template. Thus, in these cells there is no pterin-dependent
      tyrosine hydroxylase that can contribute to pigment formation by producing
      priming amounts of l-dopa for proper function of tyrosinase.

PMID- 15250937
TI  - Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase
      (Dct) and synergistic activation of Dct expression with Mitf.
AB  - The murine dopachrome tautomerase (Dct) gene is expressed early in melanocyte
      development during embryogenesis, prior to other members of the tyrosinase gene
      family important for regulating pigmentation. We have used deletion mutants of
      the Dct promoter, transfections with developmentally relevant transcription
      factors, and gel shift assays to define transcriptional determinants of Dct
      expression. Deletion mutagenesis studies show that sequences within the proximal
      459 nucleotides are critical for high level expression in melanocytic cells. This
      region of the promoter contains candidate binding sites for the transcription
      factors Sox10 and Mitf. Transfections into 293T and NIH3T3 cells show that Sox10
      and Mitf independently activate Dct expression, and, when co-transfected,
      synergistically activate Dct expression. To support the notion that Sox10 acts
      directly upon the Dct promoter to activate gene expression, direct interaction of
      Sox10 was demonstrated using gel shifts of oligonucleotide probes derived from
      promoter sequences within the region required for Sox10-dependent induction.
      These results suggest that a combinatorial transcription factor interaction is
      important for expression of Dct in neural crest-derived melanocytes, and support
      a model for sequential gene activation in melanocyte development whereby Mitf, a
      Sox10-dependent transcription factor, is expressed initially before an early
      melanocyte differentiation gene, Dct, is expressed.

PMID- 15250938
TI  - A transgenic mouse model with inducible Tyrosinase gene expression using the
      tetracycline (Tet-on) system allows regulated rescue of abnormal chiasmatic
      projections found in albinism.
AB  - Congenital defects in retinal pigmentation, as in oculocutaneous albinism Type I
      (OCA1), where tyrosinase is defective, result in visual abnormalities affecting
      the retina and pathways into the brain. Transgenic animals expressing a
      functional tyrosinase gene on an albino genetic background display a correction
      of all these abnormalities, implicating a functional role for tyrosinase in
      normal retinal development. To address the function of tyrosinase in the
      development of the mammalian visual system, we have generated a transgenic mouse
      model with inducible expression of the tyrosinase gene using the tetracycline
      (TET-ON) system. We have produced two types of transgenic mice: first, mice
      expressing the transactivator rtTA chimeric protein under the control of mouse
      tyrosinase promoter and its locus control region (LCR), and; second, transgenic
      mice expressing a mouse tyrosinase cDNA construct driven by a minimal promoter
      inducible by rtTA in the presence of doxycycline. Inducible experiments have been
      carried out with selected double transgenic mouse lines. Tyrosinase expression
      has been induced from early embryo development and its impact assessed with
      histological and biochemical methods in heterozygous and homozygous double
      transgenic individuals. We have found an increase of tyrosinase activity in the
      eyes of induced animals, compared with littermate controls. However, there was
      significant variability in the activation of this gene, as reported in analogous
      experiments. In spite of this, we could observe corrected uncrossed chiasmatic
      pathways, decreased in albinism, in animals induced from their first gestational
      week. These mice could be instrumental in revealing the role of tyrosinase in
      mammalian visual development.

PMID- 15250939
TI  - Down-regulated PAR-2 is associated in part with interrupted melanosome transfer
      in pigmented basal cell epithelioma.
AB  - In pigmented basal cell epithelioma (BCE), there seems to be an abnormal transfer
      of melanized melanosomes from proliferating melanocytes to basaloid tumor cells.
      In this study, the interruption of that melanosome transfer was studied with
      special respect to the altered function of a phagocytic receptor, protease
      activated receptor (PAR)-2 in the basaloid tumor cells. We used electron
      microscopy to clarify the disrupted transfer at the ultrastructural level and
      then performed immunohistochemistry and reverse transcription-polymerase chain
      reaction (RT-PCR) to examine the regulation of a phagocytic receptor, PAR-2,
      expressed on basaloid tumor cells. Electron microscopic analysis revealed that
      basaloid tumor cells of pigmented BCE have a significantly lower population of
      melanosomes ( approximately 16.4%) than do normal keratinocytes located in the
      perilesional normal epidermis ( approximately 91.0%). In contrast, in pigmented
      seborrheic keratosis (SK), a similarly pigmented epidermal tumor, the
      distribution of melanin granules does not differ between the lesional (
      approximately 93.9%) and the perilesional normal epidermis ( approximately 92.2
      %), indicating that interrupted melanosome transfer occurs in BCE but not in all
      pigmented epithelial tumors. RT-PCR analysis demonstrated that the expression of
      PAR-2 mRNA transcripts in basaloid cells is significantly decreased in pigmented
      BCE compared with the perilesional normal epidermis. In contrast, in pigmented
      SK, where melanosome transfer to basaloid tumor cells is not interrupted, the
      expression of PAR-2 mRNA transcripts is comparable between the basaloid tumor
      cells and the perilesional normal epidermis. Immunohistochemistry demonstrated
      that basaloid cells in pigmented BCE have less immunostaining for PAR-2 than do
      keratinocytes in the perilesional normal epidermis whereas in pigmented SK, there
      is no difference in immunostaining for PAR-2 between the basaloid tumor and the
      perilesional normal epidermis. These findings suggest that the decreased
      expression of PAR-2 in the basaloid cells is associated in part with the observed
      interruption of melanosome transfer in pigmented BCE.

PMID- 15250940
TI  - Near infrared spectroscopy as a tool for the determination of eumelanin in human
      hair.
AB  - Eumelanins are brown-black pigments present in the hair and in the epidermis
      which are acknowledged as protection factors against cell damage caused by
      ultraviolet radiation. The quantity of eumelanin present in hair has recently
      been put forward as a means of identifying subjects with a higher risk of skin
      tumours. For epidemiological studies, chromatographic methods of determining
      pyrrole-2,3,5-tricarboxylic acid (PTCA; the principal marker of eumelanin) are
      long, laborious and unsuitable for screening large populations. We suggest near
      infrared (NIR) spectroscopy as an alternative method of analysing eumelanin in
      hair samples. PCTA was determined on 93 samples of hair by means of oxidizing
      with hydrogen peroxide in a basic environment followed by chromatographic
      separation. The same 93 samples were then subjected to NIR spectrophotometric
      analysis. The spectra were obtained in reflectance mode on hair samples which had
      not undergone any preliminary treatment, but had simply been pressed and placed
      on the measuring window of the spectrophotometer. The PTCA values obtained by
      means of HPLC were correlated with the near infrared spectrum of the respective
      samples. A correlation between the PTCA values obtained by means of HPLC and the
      PTCA values obtained from an analysis of the spectra was obtained using the
      principal component regression (PCR) algorithm. The correlation obtained has a
      coefficient of regression (R(2)) of 0.89 and a standard error of prediction (SEP)
      of 13.8 for a mean value of 108.6 ng PTCA/mg hair. Some considerations about the
      accuracy of the obtained correlation and the main sources of error are made and
      some validation results are shown.

PMID- 15250941
TI  - Agonist-independent, high constitutive activity of the human melanocortin 1
      receptor.
AB  - The melanocortins (alpha-melanocyte-stimulating hormone and adrenocorticotropin)
      act on epidermal melanocytes to increase melanogenesis, the eumelanin/pheomelanin
      ratio and dendricity. These actions are mediated by the heptahelical melanocortin
      1 receptor (MC1R), positively coupled to adenylyl cyclase. Gain-of-function mouse
      Mc1r alleles are associated with a dark, eumelanic coat. Conversely, loss-of
      function variants, or overexpression of agouti, a natural melanocortin
      antagonist, yield yellow, pheomelanic furs. In humans, loss-of-function MC1R
      variants are associated with fair skin, poor tanning, propensity to freckle and
      increased skin cancer risk. Therefore, MC1R is a key regulator of mammalian
      pigmentation. Several observations such as induction of constitutive pigmentation
      in amelanotic mouse melanoma cells following expression of MC1R indicate that the
      receptor might display agonist-independent activity. We report a systematic and
      comparative study of MC1R and Mc1r constitutive activity. We show that expression
      of MC1R in heterologous systems leads to an agonist-independent increase in
      cyclic adenosine monophophate (cAMP). Basal signalling is a function of receptor
      expression and is two to fourfold higher for MC1R than for Mc1r. Moreover, it is
      observed in human melanoma cells over-expressing the MC1R. Constitutive
      signalling is abolished or reduced by point mutations of MC1R impairing the
      response to agonists, and is only doubled by the Lys94Glu mutation, mimicking the
      constitutively active mouse E(so-3J) allele. Stable or transient expression of
      wild-type MC1R, but not of loss-of-function mutants, potently stimulates
      forskolin activation of adenylyl cyclase, a common feature of constitutively
      active Gs-coupled receptors. Therefore, human MC1R displays a strong agonist
      independent constitutive activity.

PMID- 15250942
TI  - 25-hydroxycholesterol acts in the Golgi compartment to induce degradation of
      tyrosinase.
AB  - Oxysterols play a significant role in cholesterol homeostasis. 25
      Hydroxycholesterol (25HC) in particular has been demonstrated to regulate
      cholesterol homeostasis via oxysterol-binding protein and oxysterol-related
      proteins, the sterol regulatory element binding protein, and the rate-limiting
      enzyme of cholesterol biosynthesis, hydroxymethylglutaryl coenzyme A reductase.
      We have examined the effect of 25HC on pigmentation of cultured murine
      melanocytes and demonstrated a decrease in pigmentation with an IC(50) of 0.34
      microM and a significant diminution in levels of melanogenic protein tyrosinase.
      Pulse-chase studies of 25HC-treated cells demonstrated enhanced degradation of
      tyrosinase, the rate-limiting enzyme of melanin synthesis, following endoplasmic
      reticulum (ER) and Golgi maturation. Protein levels of GS28, a member of an
      ER/cis-Golgi SNARE protein complex, were also diminished in 25HC-treated
      melanocytes, however levels of the ER chaperone calnexin and the cis-Golgi matrix
      protein GM130 were unaffected. Effects of 25HC on tyrosinase were completely
      reversed by 4 alpha-allylcholestan-3 alpha-ol, a sterol identified by its ability
      to reverse effects of 25HC on cholesterol homeostasis. Finally, the addition of
      25HC to lipid deficient serum inhibited correct processing of tyrosinase. We
      conclude that 25HC acts in the Golgi compartment to regulate pigmentation by a
      mechanism shared with cholesterol homeostasis.

PMID- 15250943
TI  - Novel approach for evaluation of estrogenic and anti-estrogenic activities of
      genistein and daidzein using B16 melanoma cells and dendricity assay.
AB  - The effects of soy isoflavones, genistein and daidzein, which exhibit estrogenic,
      anti-estrogenic and/or tyrosine kinase inhibitory activity, on the dendritic
      morphology of B16 mouse melanoma cells were quantitatively evaluated and compared
      with those of 17 beta-estradiol (Est) and tyrphostin, a tyrosine kinase
      inhibitor. Dendricity was significantly stimulated in the order of Est >>
      genistein > daidzein = tyrphostin, but not by glycosides of genistein and
      daidzein. In competition experiments, Est counteracted the stimulatory activity
      of genistein and daidzein, but enhanced the activity of tyrphostin additively,
      suggesting that genistein and daidzein agonized Est. In addition, when the
      concentration ratios of genistein/Est and daidzein/Est were higher than 5000 and
      50,000, respectively, genistein and daidzein agonized Est. In contrast, when the
      ratio of daidzein/Est was lower than 500, daidzein antagonized Est. Furthermore,
      genistein and daidzein competed with each other in stimulatory activity. These
      observations suggest that: 1) dendricity is stimulated by agonists (genistein and
      daidzein) of Est and tyrosine kinase inhibitors (genistein and tyrphostin), 2)
      the concentration ratio of isoflavone aglycone/Est is very important as one
      regulatory factor for estrogenic and/or anti-estrogenic activity, and 3) daidzein
      antagonizes not only Est but also genistein. It is concluded that a quantitative
      and simple dendricity assay using B16 mouse melanoma cells is available to
      evaluate estrogenic and anti-estrogenic activity in vitro.

PMID- 15250944
TI  - Molecular cloning, gene expression in albino mutants and gene knockdown studies
      of tyrosinase mRNA in rainbow trout.
AB  - Tyrosinase has a role in melanin synthesis and several defects of the tyrosinase
      gene lead to albinism. Here, we cloned and characterized rainbow trout tyrosinase
      cDNAs and carried out the molecular and biochemical characterization of albino
      mutants. Two types of cDNA were cloned: tyrosinase-1 (Tyr-1) and tyrosinase-2
      (Tyr-2). Both contained regions predicted to encode structural features of
      tyrosinase, and phylogenetic analysis confirmed that Tyr-1 and Tyr-2 were members
      of the tyrosinase family. Tyr-1 transcripts were first detected in embryos at 5 d
      post-fertilization (dpf) and Tyr-2 transcripts at 15 dpf. 3,4
      dihydroxyphenylalanine assays revealed significantly reduced tyrosinase
      activities in dominant and recessive albino mutants compared with wild-type
      embryos. However, reverse-transcription PCR showed no differences in the amounts
      or lengths of the coding regions of Tyr-1 and Tyr-2 transcripts between wild-type
      embryos and albino mutants. Antisense morpholino oligonucleotides (AMOs) designed
      to knockdown tyrosinase gene expression in wild-type embryos led to reduced
      pigmentation in the retina and skin of embryos at 25 and 35 dpf, respectively.
      Furthermore, the tyrosinase activities of AMO-treated embryos were significantly
      reduced. We conclude that both Tyr-1 and Tyr-2 are crucial for melanin synthesis
      in rainbow trout embryos. Furthermore, we describe a potential application of
      AMOs in the treatment of hyperpigmentation.

PMID- 15250945
TI  - The chemical structure of melanin.

PMID- 15251030
TI  - Facile synthesis of Nalpha-protected-L-alpha,gamma-diaminobutyric acids mediated
      by polymer-supported hypervalent iodine reagent in water.
AB  - Hofmann rearrangement of Nalpha-Boc-L-Gln-OH mediated by a polymer-supported
      hypervalent iodine reagent poly[(4-diacetoxyiodo)styrene] (PSDIB) in water
      afforded Nalpha-Boc-L-alpha,gamma-diaminobutyric acid (Boc-Dab-OH, 1) in 87%
      yield. Nalpha-Z-derivative (Z-Dab-OH, 2) was prepared with PSDIB in 83% yield.
      Since the reaction of Nalpha-Fmoc-Gln-OH by this procedure did not proceed
      because of the insolubility of Fmoc-Gln-OH in aqueous media, we synthesized Fmoc
      Dab(Boc)-OH (5) from 2 in 54% yield. Polymyxin B heptapeptide (PMBH) which
      contains four Dab residues was successfully synthesized in a solution-phase
      synthesis.

PMID- 15251031
TI  - A hexamer peptide ligand that binds selectively to staphylococcal enterotoxin B:
      isolation from a solid phase combinatorial library.
AB  - By screening a solid-phase combinatorial peptide library, a short peptide ligand,
      YYWLHH, has been discovered that binds with high affinity and selectivity to
      staphylococcal enterotoxin B (SEB), but only weakly to other SEs that share
      sequence and structural homology with SEB. Using column affinity chromatography
      with an immobilized YYWLHH stationary phase, it was possible to separate SEB
      quantitatively from Staphylococcus aureus fermentation broth, a complex mixture
      of proteins, carbohydrates and other biomolecules. The immobilized peptide was
      also used to purify native SEB from a mixture containing denatured and hydrolyzed
      SEB, and showed little cross-reactivity with other SEs. To our knowledge this is
      the first report of a highly specific short peptide ligand for SEB. Such a ligand
      is a potential candidate to replace antibodies for detection, removal and
      purification strategies for SEB.

PMID- 15251032
TI  - A cumulative experience examining the effect of natural and synthetic
      antimicrobial peptides vs. Chlamydia trachomatis.
AB  - We tested the activity of 48 structurally diverse antimicrobial peptides against
      Chlamydia trachomatis, serovar L2. The peptides' activity against C. trachomatis,
      serovar L2 was measured in 48-h McCoy cell shell vial assays. Peptides of 16-20
      amino acids were more active than larger peptides, such as defensins. Beta-sheet
      protegrins, as well as alpha-helical peptides such as novispirin (G-10) were
      equally active. Enantiomers were as active as native structures. Moderate-sized
      circular mini-defensins were less effective against C. trachomatis. Moderate
      sized cationic peptides may be useful in microbicide preparations designed to
      prevent chlamydial infection.

PMID- 15251033
TI  - Synthesis and modification of dibenzylglycine derivatives via the Suzuki-Miyaura
      cross-coupling reaction.
AB  - The objective of this paper is to describe in details of various available
      methods to prepare C(alpha,alpha)-dibenzylglycine (Dbzg) and then include our
      work involving the synthesis of side chain Dbzg derivatives. alpha,alpha
      Disubstituted amino acids (alpha,alphaAAs) are important members in the family of
      modified amino acids. Replacement of the alpha-hydrogens of glycine 1 by alkyl
      groups leads to alpha,alphaAAs. The steric hindrance of the quaternary centre of
      Aib 2 combined with the helix-forming capacity has attracted the attention of
      structural biologists and protein crystallographers. Dbzg 3 is a special
      structural variant of Aib. The presence of two benzyl groups at C(alpha)-position
      not only impart rigidity to the peptide backbone in which it is incorporated, but
      also acts as a useful vehicle for studying pi-pi interactions. Although several
      C(alpha,alpha)-disubstituted glycines such as C(alpha,alpha)-diethyl glycine
      (Deg), C(alpha,alpha)-dipropyl glycine (Dpg) etc. have been studied in detail,
      not much has been known about Dbzg because of limited availability of synthetic
      procedures. Various Dbzg derivatives 19a-f have been prepared using ethyl
      isocyanoacetate 14 as a glycine equivalent (eq.). A useful and simple methodology
      has been developed using the Suzuki-Miyaura cross-coupling reaction for the
      modification of Dbzg derivatives 17d, 19d, 22. Using this 'Building Block
      Approach' (Accounts of Chemical Research 36, 2003, 342) one can generate a
      variety of Dbzg derivatives 20a-f and 23a-e, which may find useful applications
      in combinatorial synthesis and QSAR studies.

PMID- 15251034
TI  - Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing
      cholangitis: a randomised controlled trial [ISRCTN88246634].
AB  - BACKGROUND: Fatigue is a major clinical problem in many patients with primary
      biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). An effective
      treatment has not been defined. Recently, a large proportion of patients with
      these diseases was found to have symptoms of depression. Because fatigue is a
      frequent symptom of depression and there is some evidence that treatment with an
      antidepressant improves fatigue in patients with fibromyalgia, we hypothesised
      that the antidepressant fluvoxamine might improve fatigue related to PBC and PSC.
      METHODS: Fatigued patients were randomised to receive fluvoxamine (75 mg BID) or
      placebo for a six-week period. Fatigue and quality of life were quantified using
      a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional
      Fatigue Inventory and the SF-36. RESULTS: Seventeen and 16 patients were
      allocated to fluvoxamine and placebo, respectively. There was no statistically
      significant beneficial effect of fluvoxamine on fatigue or quality of life. The
      median VAS scores in the fluvoxamine and placebo groups were 7.40 and 7.45 at day
      0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks
      after treatment discontinuation. CONCLUSION: We found no evidence for a
      beneficial effect of fluvoxamine on fatigue in these patients with cholestatic
      liver disease and severe chronic fatigue.

PMID- 15251035
TI  - Evaluating heterogeneity in cumulative meta-analyses.
AB  - BACKGROUND: Recently developed measures such as I2 and H allow the evaluation of
      the impact of heterogeneity in conventional meta-analyses. There has been no
      examination of the development of heterogeneity in the context of a cumulative
      meta-analysis. METHODS: Cumulative meta-analyses of five smoking cessation
      interventions (clonidine, nicotine replacement therapy using gum and patch,
      physician advice and acupuncture) were used to calculate I2 and H. These values
      were plotted by year of publication, control event rate and sample size to trace
      the development of heterogeneity over these covariates. RESULTS: The cumulative
      evaluation of heterogeneity varied according to the measure of heterogeneity used
      and the basis of cumulation. Plots produced from the calculations revealed areas
      of heterogeneity useful in the consideration of potential sources for further
      study. CONCLUSION: The examination of heterogeneity in conjunction with summary
      effect estimates in a cumulative meta-analysis offered valuable insight into the
      evolution of variation. Such information is not available in the context of
      conventional meta-analysis and has the potential to lead to the development of a
      richer picture of the effectiveness of interventions.

PMID- 15251036
TI  - Activation of muscarinic acetylcholine receptors elicits pigment granule
      dispersion in retinal pigment epithelium isolated from bluegill.
AB  - BACKGROUND: In fish, melanin pigment granules in the retinal pigment epithelium
      disperse into apical projections as part of the suite of responses the eye makes
      to bright light conditions. This pigment granule dispersion serves to reduce
      photobleaching and occurs in response to neurochemicals secreted by the retina.
      Previous work has shown that acetylcholine may be involved in inducing light
      adaptive pigment dispersion. Acetylcholine receptors are of two main types,
      nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled
      receptor superfamily, and five different muscarinic receptors have been
      molecularly cloned in human. These receptors are coupled to adenylyl cyclase,
      calcium mobilization and ion channel activation. To determine the receptor
      pathway involved in eliciting pigment granule migration, we isolated retinal
      pigment epithelium from bluegill and subjected it to a battery of cholinergic
      agents. RESULTS: The general cholinergic agonist carbachol induces pigment
      granule dispersion in isolated retinal pigment epithelium. Carbachol-induced
      pigment granule dispersion is blocked by the muscarinic antagonist atropine, by
      the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule
      dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]
      4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4
      antagonist tropicamide failed to block carbachol-induced dispersion, and the M2
      agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion.
      CONCLUSIONS: Our results suggest that carbachol-mediated pigment granule
      dispersion occurs through the activation of Modd muscarinic receptors, which in
      other systems couple to phosphoinositide hydrolysis and elevation of
      intracellular calcium. This conclusion must be corroborated by molecular studies,
      but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment
      dispersion.

PMID- 15251037
TI  - High-level gene expression in Aedes albopictus cells using a baculovirus Hr3
      enhancer and IE1 transactivator.
AB  - BACKGROUND: Aedes aegypti is the key vector of both the Yellow Fever and Dengue
      Fever viruses throughout many parts of the world. Low and variable transgene
      expression levels due to position effect and position effect variegation are
      problematic to efforts to create transgenic laboratory strains refractory to
      these viruses. Transformation efficiencies are also less than optimal, likely due
      to failure to detect expression from all integrated transgenes and potentially
      due to limited expression of the transposase required for transgene integration.
      RESULTS: Expression plasmids utilizing three heterologous promoters and three
      heterologous enhancers, in all possible combinations, were tested. The Hr3/IE1
      enhancer-transactivator in combination with each of the constitutive heterologous
      promoters tested increased reporter gene expression significantly in transiently
      transfected Aedes albopictus C7-10 cells. CONCLUSIONS: The addition of the Hr3
      enhancer to expression cassettes and concomitant expression of the IE1
      transactivator gene product is a potential method for increasing the level of
      transgene expression in insect systems. This mechanism could also potentially be
      used to increase the level of transiently-expressed transposase in order to
      increase the number of integration events in transposon-mediated transformation
      experiments.

PMID- 15251038
TI  - Xenopus Cdc14 alpha/beta are localized to the nucleolus and centrosome and are
      required for embryonic cell division.
AB  - BACKGROUND: The dual specificity phosphatase Cdc14 has been shown to be a
      critical regulator of late mitotic events in several eukaryotes, including S.
      cerevisiae, S. pombe. C. elegans and H. sapiens. However, Cdc14 homologs have
      clearly evolved to regulate distinct cellular processes and to respond to
      regulatory signals important for these processes. The human paralogs hCdc14A and
      B are the only vertebrate Cdc14 homologues studied to date, but their functions
      are not well understood. Therefore, it is of great interest to examine the
      function Cdc14 homologs in other vertebrate species. RESULTS: We identified two
      open reading frames from Xenopus laevis closely related to human Cdc14A, called
      XCdc14alpha and XCdc14beta, although no obvious paralog of the hCdc14B was found.
      To begin a functional characterization of Xcdc14alpha and XCdc14beta, we raised
      polyclonal antibodies against a conserved region. These antibodies stained both
      the nucleolus and centrosome in interphase Xenopus tissue culture cells, and the
      mitotic centrosomes. GFP-tagged version of XCdc14alpha localized to the nucleulus
      and GFP-XCdc14beta localized to the centrosome, although not exclusively.
      XCdc14alpha was also both meiotically and mitotically phosphorylated. Injection
      of antibodies raised against a conserved region of XCdc14/beta into Xenopus
      embryos at the two-cell stage blocked division of the injected blastomeres,
      suggesting that activities of XCdc14alpha/beta are required for normal cell
      division. CONCLUSION: These results provide evidence that XCdc14alpha/beta are
      required for normal cellular division and are regulated by at least two
      mechanisms, subcellular localization and possibly phosphorylation. Due to the
      high sequence conservation between Xcdc14alpha and hCdc14A, it seems likely that
      both mechanisms will contribute to regulation of Cdc14 homologs in vertebrates.

PMID- 15251039
TI  - Clustering proteins from interaction networks for the prediction of cellular
      functions.
AB  - BACKGROUND: Developing reliable and efficient strategies allowing to infer a
      function to yet uncharacterized proteins based on interaction networks is of
      crucial interest in the current context of high-throughput data generation. In
      this paper, we develop a new algorithm for clustering vertices of a protein
      protein interaction network using a density function, providing disjoint classes.
      RESULTS: Applied to the yeast interaction network, the classes obtained appear to
      be biological significant. The partitions are then used to make functional
      predictions for uncharacterized yeast proteins, using an annotation procedure
      that takes into account the binary interactions between proteins inside the
      classes. We show that this procedure is able to enhance the performances with
      respect to previous approaches. Finally, we propose a new annotation for 37
      previously uncharacterized yeast proteins. CONCLUSION: We believe that our
      results represent a significant improvement for the inference of cellular
      functions, that can be applied to other organism as well as to other type of
      interaction graph, such as genetic interactions.

PMID- 15251040
TI  - Detection of transposable elements by their compositional bias.
AB  - BACKGROUND: Transposable elements (TE) are mobile genetic entities present in
      nearly all genomes. Previous work has shown that TEs tend to have a different
      nucleotide composition than the host genes, either considering codon usage bias
      or dinucleotide frequencies. We show here how these compositional differences can
      be used as a tool for detection and analysis of TE sequences. RESULTS: We
      compared the composition of TE sequences and host gene sequences using
      probabilistic models of nucleotide sequences. We used hidden Markov models (HMM),
      which take into account the base composition of the sequences (occurrences of
      words n nucleotides long, with n ranging here from 1 to 4) and the heterogeneity
      between coding and non-coding parts of sequences. We analyzed three sets of
      sequences containing class I TEs, class II TEs and genes respectively in three
      species: Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis
      thaliana. Each of these sets had a distinct, homogeneous composition, enabling us
      to distinguish between the two classes of TE and the genes. However the
      particular base composition of the TEs differed in the three species studied.
      CONCLUSIONS: This approach can be used to detect and annotate TEs in genomic
      sequences and complements the current homology-based TE detection methods.
      Furthermore, the HMM method is able to identify the parts of a sequence in which
      the nucleotide composition resembles that of a coding region of a TE. This is
      useful for the detailed annotation of TE sequences, which may contain an ancient,
      highly diverged coding region that is no longer fully functional.

PMID- 15251041
TI  - Mutation of exposed hydrophobic amino acids to arginine to increase protein
      stability.
AB  - BACKGROUND: One strategy to increase the stability of proteins is to reduce the
      area of water-accessible hydrophobic surface. RESULTS: In order to test it, we
      replaced 14 solvent-exposed hydrophobic residues of acetylcholinesterase by
      arginine. The stabilities of the resulting proteins were tested using
      denaturation by high temperature, organic solvents, urea and by proteolytic
      digestion. CONCLUSION: Although the mutational effects were rather small, this
      strategy proved to be successful since half of the mutants showed an increased
      stability. This stability may originate from the suppression of unfavorable
      interactions of nonpolar residues with water or from addition of new hydrogen
      bonds with the solvent. Other mechanisms may also contribute to the increased
      stability observed with some mutants. For example, introduction of a charge at
      the surface of the protein may provide a new coulombic interaction on the protein
      surface.

PMID- 15251042
TI  - Changes in the expression of NO synthase isoforms after ozone: the effects of
      allergen exposure.
AB  - BACKGROUND: The functional role of nitric oxide (NO) and various nitric oxide
      synthase (NOS) isoforms in asthma remains unclear. OBJECTIVE: This study
      investigated the effects of ozone and ovalbumin (OVA) exposure on NOS isoforms.
      METHODS: The expression of inducible NOS (iNOS), neuronal NOS (nNOS), and
      endothelial NOS (eNOS) in lung tissue was measured. Enhanced pause (Penh) was
      measured as a marker of airway obstruction. Nitrate and nitrite in
      bronchoalveolar lavage (BAL) fluid were measured using a modified Griess
      reaction. RESULTS: The nitrate concentration in BAL fluid from the OVA
      sensitized/ozone-exposed/OVA-challenged group was greater than that of the OVA
      sensitized/saline-challenged group. Methacholine-induced Penh was increased in
      the OVA-sensitized/ozone-exposed/OVA-challenged group, with a shift in the dose
      response curve to the left, compared with the OVA-sensitized/saline-challenged
      group. The levels of nNOS and eNOS were increased significantly in the OVA
      sensitized/ozone-exposed/OVA-challenged group and the iNOS levels were reduced
      compared with the OVA-sensitized/saline-challenged group. CONCLUSION: In mice,
      ozone is associated with increases in lung eNOS and nNOS, and decreases in iNOS.
      None of these enzymes are further affected by allergens, suggesting that the NOS
      isoforms play different roles in airway inflammation after ozone exposure.

PMID- 15251043
TI  - Tumor-infiltrating effector cells of alpha-galactosylceramide-induced antitumor
      immunity in metastatic liver tumor.
AB  - BACKGROUND: alpha-Galactosylceramide (alpha-GalCer) can be presented by CD1d
      molecules of antigen-presenting cells, and is known to induce a potent NKT cell
      dependent cytotoxic response against tumor cells. However, the main effector
      cells in alpha-GalCer-induced antitumor immunity are still controversial.
      METHODS: In order to elucidate the cell phenotype that plays the most important
      role in alpha-GalCer-induced antitumor immunity, we purified and analyzed tumor
      infiltrating leukocytes (TILs) from liver metastatic nodules of a colon cancer
      cell line (Colon26), comparing alpha-GalCer- and control vehicle-treated mice.
      Flow cytometry was performed to analyze cell phenotype in TILs and IFN-gamma
      ELISA was performed to detect antigen-specific immune response. RESULTS: Flow
      cytometry analysis showed a significantly higher infiltration of NK cells (DX5+,
      T cell receptor alphabeta (TCR)-) into tumors in alpha-GalCer-treated mice
      compared to vehicle-treated mice. The DX5+TCR+ cell population was not
      significantly different between these two groups, indicating that these cells
      were not the main effector cells. Interestingly, the CD8+ T cell population was
      increased in TILs of alpha-GalCer-treated mice, and the activation level of these
      cells based on CD69 expression was higher than that in vehicle-treated mice.
      Moreover, the number of tumor-infiltrating dendritic cells (DCs) was increased in
      alpha-GalCer-treated mice. IFN-gamma ELISA showed stronger antigen-specific
      response in TILs from alpha-GalCer-treated mice compared to those from vehicle
      treated mice, although the difference between these two groups was not
      significant. CONCLUSIONS: In alpha-GalCer-induced antitumor immunity, NK cells
      seem to be some of the main effector cells and both CD8+ T cells and DCs, which
      are related to acquired immunity, might also play important roles in this
      antitumor immune response. These results suggest that alpha-GalCer has a
      multifunctional role in modulation of the immune response.

PMID- 15251044
TI  - Two-fold differences are the detection limit for determining transgene copy
      numbers in plants by real-time PCR.
AB  - BACKGROUND: After transformation, plants that are homozygous and contain one copy
      of the transgene are typically selected for further study. If real-time PCR is to
      be used to determine copy number and zygosity, it must be able to distinguish
      hemizygous from homozygous and one-copy from two-copy plants. That is, it must be
      able to detect two-fold differences. RESULTS: When transgenic Nicotiana attenuata
      plants which had been previously determined by Southern analysis to contain one
      or two copies of the transgene, were analyzed by real-time PCR (2-delta delta Ct
      method), the method failed to confirm the results from the Southern analysis. In
      a second data set we analyzed offspring of a hemizygous one-copy plant, which
      were expected to segregate into three groups of offspring in a 1:2:1 ratio: no
      transgene, hemizygous, homozygous. Because it was not possible to distinguish
      homozygous from hemizygous plants with real-time PCR, we could not verify this
      segregation ratio. CONCLUSIONS: Detection of two-fold differences by real-time
      PCR is essential if this procedure is to be used for the characterization of
      transgenic plants. However, given the high variability between replicates, a
      detection of two-fold differences is in many cases not possible; in such cases
      Southern analysis is the more reliable procedure.

PMID- 15251045
TI  - Self-reported ill health in male UK Gulf War veterans: a retrospective cohort
      study.
AB  - BACKGROUND: Forces deployed to the first Gulf War report more ill health than
      veterans who did not serve there. Many studies of post-Gulf morbidity are based
      on relatively small sample sizes and selection bias is often a concern. In a
      setting where selection bias relating to the ill health of veterans may be
      reduced, we: i) examined self-reported adult ill health in a large sample of male
      UK Gulf War veterans and a demographically similar non-deployed comparison group;
      and ii) explored self-reported ill health among veterans who believed that they
      had Gulf War syndrome. METHODS: This study uses data from a retrospective cohort
      study of reproduction and child health in which a validated postal questionnaire
      was sent to all UK Gulf War veterans (GWV) and a comparison cohort of Armed
      Service personnel who were not deployed to the Gulf (NGWV). The cohort for
      analysis comprises 42,818 males who responded to the questionnaire. RESULTS: We
      confirmed that GWV report higher rates of general ill health. GWV were
      significantly more likely to have reported at least one new medical symptom or
      disease since 1990 than NGWV (61% versus 37%, OR 2.7, 95% CI 2.5-2.8). They were
      also more likely to report higher numbers of symptoms. The strongest associations
      were for mood swings (OR 20.9, 95%CI 16.2-27.0), memory loss/lack of
      concentration (OR 19.6, 95% CI 15.5-24.8), night sweats (OR 9.9, 95% CI 6.5
      15.2), general fatigue (OR 9.6, 95% CI 8.3-11.1) and sexual dysfunction (OR 4.6,
      95%CI 3.2-6.6). 6% of GWV believed they had Gulf War syndrome (GWS), and this was
      associated with the highest symptom reporting. CONCLUSIONS: Increased levels of
      reported ill health among GWV were confirmed. This study was the first to use a
      questionnaire which did not focus specifically on the veterans' symptoms
      themselves. Nevertheless, the results are consistent with those of other studies
      of post-Gulf war illness and thus strengthen overall findings in this area of
      research. Further examination of the mechanisms underlying the reporting of ill
      health is required.

PMID- 15251046
TI  - Prenatal diagnosis of pygopagus tetrapus parasitic twin: case report.
AB  - BACKGROUND: Asymmetric and parasitic conjoined twins are rarer anomalies of
      monochorionic monoamniotic twins, consisting of an incomplete twin attached to
      the fully developed body of the co-twin. CASE PRESENTATION: A 30-year-old
      multigravid woman referred to maternal fetal unit due to polyhydramnios at 28th
      week of gestation. Sonographic examination revealed a single fetus and
      polyhydramnios with amniotic fluid index 30 cm. The fetus had normal apparent
      single head, spine, thorax, abdomen, two upper and two lower limbs, and two
      relatively well developed rudimentary parasitic lower limbs at sacral region.
      Lower limbs of the autosite were moving freelly but no movement was detected at
      the parasite. The parasite contained irregular lower limbs and left foot with
      three toes. Short and deformed long bones were also present in the parasitic
      limbs. A Cesarean section was performed at 38th week of gestation and a live
      female infant weighing 3600 g was delivered. The parasitic lower limbs were
      totally excised. Post-operative period was uneventful and the newborn was
      discharged as healthy. Post-natal follow-up was normal at nine-month-old.
      CONCLUSION: Pygopagus tetrapus parasitic twin is a rare form of conjoined twins
      and in utero diagnosis with ultrasound assists in prenatal management and
      counselling with parents.

PMID- 15251047
TI  - Editorial. Public Health Nutrition as a field of practice.

PMID- 15251048
TI  - Out of the box. Report on debates held at the 2004 World Health Assembly in
      Geneva.

PMID- 15251049
TI  - Public health nutrition and food policy.
AB  - Food in its many manifestations allows us to explore the global control of health
      and to examine the ways in which food choice is moulded by many interests. The
      global food market is controlled by a small number of companies who operate a
      system that delivers 'cheap' food to the countries of the developed world. This
      'cheap' food comes at a price, which externalises costs to the nation state in
      terms of health consequences (diabetes, coronary heart disease and other food
      related diseases) and to the environment in terms of pollution and the associated
      clean-up strategies. Food policy has not to any great extent dealt with these
      issues, opting instead for an approach based on nutrition, food choice and
      biomedical health. Ignoring wider elements of the food system including issues of
      ecology and sustainability constrains a broader understanding within public
      health nutrition. Here we argue that public health nutrition, through the medium
      of health promotion, needs to address these wider issues of who controls the food
      supply, and thus the influences on the food chain and the food choices of the
      individual and communities. Such an upstream approach to food policy (one that
      has been learned from work on tobacco) is necessary if we are seriously to
      influence food choice.

PMID- 15251050
TI  - A review of the effectiveness of agriculture interventions in improving nutrition
      outcomes.
AB  - OBJECTIVES: To review the impact of agriculture interventions on nutritional
      status in participating households, and to analyse the characteristics of
      interventions that improved nutrition outcomes. DESIGN: We identified and
      reviewed reports describing 30 agriculture interventions that measured impact on
      nutritional status. The interventions reviewed included home gardening,
      livestock, mixed garden and livestock, cash cropping, and irrigation. We examined
      the reports for the scientific quality of the research design and treatment of
      the data. We also assessed whether the projects invested in five types of
      'capital' (physical, natural, financial, human and social) as defined in the
      Sustainable Livelihoods Framework, a conceptual map of major factors that affect
      people's livelihoods. RESULTS: Most agriculture interventions increased food
      production, but did not necessarily improve nutrition or health within
      participating households. Nutrition was improved in 11 of 13 home gardening
      interventions, and in 11 of 17 other types of intervention. Of the 19
      interventions that had a positive effect on nutrition, 14 of them invested in
      four or five types of capital in addition to the agriculture intervention. Of the
      nine interventions that had a negative or no effect on nutrition, only one
      invested in four or five types of capital. CONCLUSIONS: Those agriculture
      interventions that invested broadly in different types of capital were more
      likely to improve nutrition outcomes. Those projects which invested in human
      capital (especially nutrition education and consideration of gender issues), and
      other types of capital, had a greater likelihood of effecting positive
      nutritional change, but such investment is neither sufficient nor always
      necessary to effect change.

PMID- 15251051
TI  - Are infant feeding options that are recommended for mothers with HIV acceptable,
      feasible, affordable, sustainable and safe? Pregnant women's perspectives.
AB  - OBJECTIVE: To investigate pregnant women's views on infant feeding options
      recommended for HIV-infected women. DESIGN: A structured interview survey
      complemented with focus group discussions. SETTING: Antenatal clinics in Moshi
      urban and rural districts of Tanzania. SUBJECTS: Five hundred pregnant women
      participated in the interview survey and 46 pregnant women participated in six
      focus group discussions. RESULTS: Participating women reported that they would
      change to an alternative infant feeding method if they were found to be HIV
      infected and were advised to do so. Cow's milk was regarded as the most feasible
      infant feeding method for local HIV-infected mothers. Infant feeding formula was
      regarded as too costly, but if recommended by health workers and distributed free
      of charge, the majority of the women (82%) were confident that they would then
      choose this option. In the focus group discussions, women were less optimistic
      and expressed great concern for the social consequences of not breast-feeding.
      The safety of exclusive breast-feeding was questioned. Less common infant feeding
      methods, such as expressed heat-treated breast milk and wet-nursing, were not
      regarded as viable options. Several social barriers to replacement feeding were
      identified in the focus group discussions, including possible lack of support
      from partner and potential negative reactions from the community. CONCLUSION:
      Future research on infant feeding options should include the broader cultural
      context and the psychological stress that HIV-infected women face when choosing
      infant feeding methods.

PMID- 15251052
TI  - Nine months postpartum weight retention predictors for Brazilian women.
AB  - OBJECTIVE: To identify factors potentially associated with weight retention
      measured 9 months after childbirth. DESIGN: Prospective study with four follow-up
      waves in time (0.5, 2, 6 and 9 months postpartum). SETTING: Rio de Janeiro,
      Brazil. SUBJECTS AND METHODS: Two hundred and sixty-six Brazilian women of
      childbearing age. Analysis was based on hierarchical logistic regression. The
      dependent variable was weight retention and was defined as the difference between
      weight at 9 months postpartum and pre-pregnancy weight, with a dichotomised cut
      off at 7.5 kg. Covariates included demographic and socio-economic data, obstetric
      history, anthropometric data, and data on the infant. These data were grouped in
      blocks and ordered according to their influence on the dependent variable.
      RESULTS: Of the women studied, 19.2% presented weight retention values > or =7.5
      kg. According to the logistic regression analysis, the following variables
      remained associated with weight retention > or =7.5 kg: total family income,
      difficulty or inability to read a letter, age category > or =30 years, age at
      first childbirth <23 years, gestational weight gain > or =12 kg, body fat at
      baseline > or =30% and infant birth weight <3500 g. Infant hospitalisation was
      only marginally significant. CONCLUSIONS: Determinant factors identified by the
      analysis highlight the need for nutritional intervention policies during
      pregnancy and in the first months postpartum as a way of minimising obesity and
      the diseases resulting from it.

PMID- 15251053
TI  - Waist circumference as a determinant of hypertension and diabetes in Brazilian
      women: a population-based study.
AB  - OBJECTIVE: To evaluate the role of central adiposity, as evaluated by the
      measurement of waist circumference (WC), as an independent risk factor for
      hypertension and type 2 diabetes mellitus in the setting of a developing country.
      DESIGN: Population-based, cross-sectional study. SETTING: A medium-sized town in
      southern Brazil. PARTICIPANTS: One thousand and ninety-five non-pregnant women,
      20 to 69 years old, recruited by cluster random sampling between 1999 and 2000.
      Their mean WC was 85.3 cm (standard deviation 13.9 cm) and 23.3% (n=255) were
      obese (body mass index >30 kg m(-2)). The prevalence of hypertension and diabetes
      was 25.6% (n=280) and 6.2% (n=68), respectively. RESULTS: The risks of
      hypertension and diabetes were directly related to WC measurement. Women with
      WC>80 cm had increased risk of hypertension (odds ratio (OR)=6.2, P<0.001). The
      association remained significant (OR=1.04 per cm increase in WC, P=0.02) after
      adjusting for confounders. The effect of WC on diabetes was modified by age. The
      effect was stronger in women younger than 40 years old (OR=12.7, P=0.016) than in
      those over 40 years old (OR=2.8, P=0.013). In the multivariate analysis, the odds
      ratio was 5.7 (P=0.12) in those under 40 years old and 2.8 (P=0.008) in older
      women. CONCLUSIONS: Waist circumference is an independent determinant for
      hypertension and diabetes in women in this population. The stronger association
      between WC and diabetes in younger women suggests that the validity of this
      indicator to assess abdominal adiposity is age-specific. Further studies should
      validate the usefulness of WC measurement in different age groups.

PMID- 15251054
TI  - Secular trends in diet among elderly Swedes -- cohort comparisons over three
      decades.
AB  - OBJECTIVE: The purpose of this study was to compare dietary practices among
      different birth cohorts of 70-year-old Swedes, who were examined between 1971 and
      2000. SETTING: Goteborg, Sweden. DESIGN: Four population-based samples of 1360 70
      year-olds, born in 1901, 1911, 1922 and 1930, have undergone health examinations
      and dietary assessments over a period of almost three decades. One-hour diet
      history (DH) interviews were conducted in 1971, 1981, 1992 and 2000 with a total
      of 758 women and 602 women. The formats and contents of the dietary examinations
      were similar over the years. Statistical analysis of linear trends was conducted,
      using year of examination as the independent variable, to detect secular trends
      in food and nutrient intakes across cohorts. RESULTS: At the 2000 examination,
      the majority of 70-year-olds consumed nutritionally adequate diets. Later-born
      cohorts consumed more yoghurt, breakfast cereals, fruit, vegetables, chicken,
      rice and pasta than earlier-born cohorts. Consumption of low-fat spread and milk
      also increased, along with that of wine, light beer and candy. In contrast,
      potatoes, cakes and sugar were consumed less in 2000 than in 1971. The ratio of
      reported energy intake to estimated basal metabolic rate did not show any
      systematic trend over time in women, but showed a significant upward trend in
      men. CONCLUSIONS: The diet history method has captured changes in food selections
      in the elderly without changing in general format over three decades. Dietary
      quality has improved in a number of ways, and these findings in the elderly are
      consistent with national food consumption trends in the general population.

PMID- 15251055
TI  - Prevalence of overweight and obesity in adolescent Tehrani students, 2000-2001:
      an epidemic health problem.
AB  - OBJECTIVE: Overweight has become a public health problem in most developing
      countries. Evidence suggests that adolescence is a critical period in determining
      adulthood obesity and its complications. The present study was carried out to
      assess the prevalence of overweight and obesity among secondary school students.
      DESIGN AND SETTING: This descriptive study was conducted in Tehran city, 2000
      2001. Body weight and height were measured and body mass index (BMI) values were
      calculated. Underweight, overweight and obesity were defined as <5th, > or = 85th
      and > or = 95th percentile, respectively, of age- and sex-specific BMI values
      from the National Center for Health Statistics/Centers for Disease Control and
      Prevention (2000). SUBJECTS: Using a multistage sampling method, 2321 students
      (1068 males and 1253 females) aged 11-16 years were assessed in Tehran, the
      capital city of Iran. RESULTS: The overall prevalences of overweight and obesity
      were 21.1 and 7.8%, respectively. The prevalence of overweight among girl
      students (i.e. 23.1%; 95% confidence interval (CI) 20.8-25.4) was significantly
      higher than that among boys (i.e. 18.8%; 95% CI 16.5-21.1, P=0.01) even after
      adjustment for age (odds ratio 1.26, 95% CI 1.03-1.55, P=0.02). No significant
      risk of obesity associated with age was found in girls or boys. In both sexes,
      median values of age-specific BMI in this study were statistically higher than
      corresponding values collected in Tehrani adolescents 10 years ago (P=0.03).
      Similarly, a significant difference was seen between girl students in this study
      and the reference population (P=0.03). CONCLUSION: According to this study,
      overweight, especially in girls, should be considered an epidemic health problem
      among adolescent students in Tehran.

PMID- 15251056
TI  - The relationship between education and food consumption in the 1995 Australian
      National Nutrition Survey.
AB  - OBJECTIVE: To assess the relationship between education and the intake of a
      variety of individual foods, as well as groups of foods, for Australian men and
      women in different age groups. DESIGN: Cross-sectional national survey of free
      living men and women. SUBJECTS: A sample of 2501 men and 2739 women aged 18 years
      and over who completed the National Nutrition Survey (NNS) 1995. METHODS:
      Information about the frequency of consumption of 88 food items was obtained
      using a food-frequency questionnaire in a nation-wide nutrition survey. Irregular
      and regular consumers of foods were identified according to whether they consumed
      individual foods less than or more than once per month. The relationship between
      single foods and an index of education (no post-school qualifications,
      vocational, university) was analysed via contingency table chi-square statistics
      for men and women. Food group variety scores were derived by assigning individual
      foods to conventional food group taxonomies, and then summing the dichotomised
      intake scores for individual foods within each food group. Two-way analyses of
      variance (education by age groups) were performed on food variety scores for men
      and women, separately. RESULTS: While university-educated men and women consumed
      many individual foods more regularly than less-educated people, they were less
      likely to be regular consumers of several meat products. The relationship between
      education and food consumption was less apparent when individual food scores were
      aggregated into food group scores. University-educated men and women exhibited
      higher scores on total food group variety than the other educational groups.
      CONCLUSIONS: Higher education is associated with the regular consumption of a
      wider variety of foods. Aggregation of individual food consumption indices into
      food variety scores may mask the apparent effects of educational background on
      food consumption.

PMID- 15251057
TI  - Promotions to increase lower-fat food choices among students in secondary
      schools: description and outcomes of TACOS (Trying Alternative Cafeteria Options
      in Schools).
AB  - OBJECTIVES: (1) To describe promotional activities, particularly student-led,
      targeting lower-fat a la carte foods that were conducted in secondary schools;
      and (2) to describe the relationships between the number and duration of total
      promotional activities for lower-fat a la carte foods and cafeteria sales of such
      foods over two years. DESIGN: Promotional activities were implemented in schools
      that were randomised to the intervention condition of a larger, two-year, school
      based, randomised, controlled nutrition intervention trial. SETTING: Ten
      Minnesota secondary schools. SUBJECTS: Students and school faculty, school food
      service and research staff (measured at the school level). RESULTS: Over two
      years, 181 promotions were implemented (n=49 in Year 1 and n=132 in Year 2). In
      Year 1, the number of promotions conducted in schools was significantly
      associated with percentage lower-fat food sales. In Year 2, the duration of
      promotions was significantly associated with percentage lower-fat food sales.
      CONCLUSIONS: Collaborative efforts among students, school food-service staff and
      research staff can be successful in implementing a large number of nutrition
      related, school-wide promotional activities. These efforts can increase the sales
      of lower-fat foods in a la carte areas of school cafeterias.

PMID- 15251058
TI  - Underreporting of energy intake from a self-administered food-frequency
      questionnaire completed by adults in Montreal.
AB  - BACKGROUND: Energy intake determined from self-reported dietary assessment
      methods may be underreported. Therefore, it is important that such methods be
      validated against another with known validity for energy intake or energy
      expenditure. METHODS: We investigated potential underestimation of energy intake
      obtained from our semi-quantitative food-frequency questionnaire (FFQ)
      administered between 2000 and 2001 in the metropolitan area of Montreal, Canada.
      The study population included 246 adults aged 18 to 82 years. The ratio of energy
      intake to estimated basal metabolic rate (EI/BMR) was used to assess
      underreporting and physical activity was determined from self-administered
      questions. Comparison of the EI/BMR ratio with the Goldberg statistical cut-off
      allowed us to detect individuals who were low energy reporters (LERs). LERs and
      non-LERs were compared to determine if they differed on sociodemographic,
      anthropometric and lifestyle variables. RESULTS: The EI/BMR ratio was 1.26 for
      men and 1.32 for women. LERs represented 43% of the sample of individuals. Male
      LERs accounted for 54% compared with 35% among females. Underreporting of energy
      intake was highest in men and individuals who were older, heavier, with higher
      body mass index and lower education level. A higher proportion of male LERs
      perceived their financial situation as adequate while a greater proportion of
      female LERs considered themselves poor. CONCLUSION: Our data suggest that
      underreporting of energy intake from the FFQ was considerable and may bias
      dietary interpretation. As this was uneven across the sample, it is crucial to
      recognise the characteristics of LERs in order to increase the validity of
      reported energy intake.

PMID- 15251059
TI  - Competencies for effective public health nutrition practice: a developing
      consensus.
AB  - OBJECTIVES: To assess the level of consensus amongst an international panel of
      public health nutrition leaders regarding the essential competencies required for
      effective public health nutrition practice. DESIGN: A modified Delphi study
      involving three rounds of questionnaires. SUBJECTS: A panel of 20 public health
      nutrition experts from seven countries in the European Union, the USA and
      Australia. RESULTS: Expert panellists completed three rounds of the study
      relating to competencies. A literature review conducted as a prelude to the
      expert panel survey identified common competency units from the fields of public
      health, health promotion, nutrition and dietetics, and health education. These
      were categorised into seven competency areas including analytical, socio-cultural
      and political, public health service, communication, management and leadership,
      nutrition science and professional competency categories. There was strong
      initial agreement (> or = 90% of panellists at Round 1) that developing
      internationally recognised competencies for public health nutrition specialists
      was a priority. Twenty-six of an initial listing of 52 competency units were
      rated as essential competencies by > or = 80% of the panellists after Round 1.
      Iteration rounds resulted in the addition of five extra competency units
      suggested by panellists after Round 1 and an increase by 13 in the number of
      competencies rated as essential to consensus levels. From a total of 57
      competency units rated after the final survey round, 41 competency units were
      rated as essential competencies by > or = 80% of the panellists (consensus), with
      21 of these unanimously rated as essential competencies. CONCLUSIONS: There is
      strong international agreement amongst public health nutrition leaders in Europe,
      the USA and Australia about a range of competencies required for effective public
      health nutrition practice. Essential competency units identified can be used to
      develop and review competency standards for public health nutrition.

PMID- 15251061
TI  - Editorial.

PMID- 15251062
TI  - Opinion piece. Genome sequencing: time to widen our horizons.

PMID- 15251063
TI  - Operomics: integrated genomic and proteomic profiling of cells and tissues.
AB  - In the post-genome era, technologies are becoming available that allow the
      profiling of tissues and cell populations at multiple levels including genomic
      (DNA and RNA), proteomic (proteins and peptides) and post-proteomic (eg
      metabolomic). Operomics refers to the molecular analysis of tissues and cells at
      the three levels that are connected through the coding process - namely, DNA, RNA
      and protein. The premise is that no one level or type of analysis fully captures
      gene expression and that functional changes at the proteome level cannot be
      simply predicted from analyses at the DNA or RNA levels. An important determinant
      that weakens a direct link between RNA and protein levels is translational
      control that differentially regulates mRNA translation. In this paper, the
      approaches for genomic and proteomic profiling and the contribution of
      translational control are reviewed.

PMID- 15251064
TI  - Proteomics: technologies and applications.
AB  - Enabling technologies for proteomics (studies examining the protein complement of
      the genome) have been in development for over 20 years. However, more recently,
      the field has become formalized by combining the techniques for large-scale
      protein separation (two-dimensional electrophoresis) with very precise, high
      fidelity approaches to the analysis and characterisation of the separated
      proteins (mass spectrometry). These approaches bring to reality the powerful
      scope of proteomics, enabling the interpretation of cell physiology through
      profiling the molecular biodescriptors of gene expression, the proteins.
      Applications of proteomics are wide ranging and can be found within many
      disciplines, although one of the more developed fields that is examined here
      covers the arena of toxicological and pharmacological profiling. In this paper,
      the current technologies that make proteomics possible will be looked at. Some
      areas where proteomics has delivered valuable biological insight will also be
      considered, and there will be a look towards future areas of development.

PMID- 15251066
TI  - Cross-species studies for target validation.
AB  - The completion of the genome sequences of several model organisms and the recent
      development of high throughput procedures to map genes, expression patterns and
      interactions is providing a steadily increasing number of candidate target genes.
      The function of most of these genes still remains unknown. Therefore, there is a
      growing demand in genetically tractable animal models in which the function of
      individual factors can be studied in large scale, particularly of those that are
      thought to segregate with human disorders. In this paper, current methods to
      validate target gene function and the advantages of different model organisms are
      compared.

PMID- 15251065
TI  - The jury is out on "guilt by association" trials.
AB  - The availability of comprehensive protein-protein interaction maps will
      significantly enhance medical research and aid the functional characterisation of
      novel genes. To date, the largest scale studies of protein-protein interactions
      have used the yeast two hybrid method. In this review we take a closer look at
      the different approaches used in these studies and discuss some key
      considerations that should be taken into account when designing high throughput
      interaction mapping projects.

PMID- 15251067
TI  - Pharmacogenetics of cardiovascular drugs.
AB  - Pharmacogenetics is a field aimed at understanding the genetic contribution to
      inter-patient variability in drug efficacy and toxicity. Treatment of
      cardiovascular disease is, in most cases, guided by evidence from well-controlled
      clinical trials. Given the solid scientific basis for the treatment of most
      cardiovascular diseases, it is common for patients with a given disease to be
      treated in essentially the same manner. Thus, the clinical trials have been very
      informative about treating large groups of patients with a given disease, but are
      slightly less informative about the treatment of individual patients.
      Pharmacogenetics and pharmacogenomics have the potential of taking the
      information derived from large clinical trials and further refining it to select
      the drugs with the greatest likelihood for benefit, and least likelihood for
      harm, in individual patients, based on their genetic make-up. In this paper, the
      current literature on cardiovascular pharmacogenetics is emphasised, and how the
      use of pharmacogenetic/pharmacogenomic information may be particularly useful in
      the future in the treatment of cardiovascular diseases is also highlighted.

PMID- 15251068
TI  - Plant genomics: present state and a perspective on future developments.
AB  - The year 2001 may well be called the Year of the Human Genome. Less in the
      limelight, but equally exciting for plant scientists, is the rapid progress in
      plant genomics. With relatively modest resources, a lot has been achieved. The
      Arabidopsis genomic sequence (125 megabases [Mb]) is essentially finished, and
      rice sequencing is progressing rapidly. For many species, expressed sequence tag
      (EST) resources are plentiful, allowing broad inter-specific comparisons. At the
      same time, development of integrated physical-genetic maps for large-genome crop
      species is not progressing as rapidly as desired, while resources for the
      complete sequencing of these crops are not likely to become available. Some
      important plant genomes are so large that their complete sequencing may not be
      practical for many years. Significant plant genome research is concentrated in
      industry, and not freely available, creating some frustration in the academic
      community. Growing interest is anticipated in the development of metabolic
      profiling technologies, RNA profiling, proteomics and integrated systems
      approaches to plant biology.

PMID- 15251069
TI  - Massively parallel signature sequencing (MPSS) as a tool for in-depth
      quantitative gene expression profiling in all organisms.
AB  - Massively parallel signature sequencing (MPSS) is one of the newest tools
      available for conducting in-depth expression profiling. MPSS is an open-ended
      platform that analyses the level of expression of virtually all genes in a sample
      by counting the number of individual mRNA molecules produced from each gene.
      There is no requirement that genes be identified and characterised prior to
      conducting an experiment. MPSS has a routine sensitivity at a level of a few
      molecules of mRNA per cell, and the datasets are in a digital format that
      simplifies the management and analysis of the data. Therefore, of the various
      microarray and non-microarray technologies currently available, MPSS provides
      many advantages for generating the type of complete datasets that will help to
      facilitate hypothesis-driven experiments in the era of digital biology.

PMID- 15251070
TI  - Dysregulation of apoptosis as mechanism supporting the induction of autoimmunity.

PMID- 15251071
TI  - Long-term outcome of fibromyalgia related to cervical spine injury is worse in
      women than in men.

PMID- 15251072
TI  - New evidence for central sensitization in patients with fibromyalgia.

PMID- 15251073
TI  - Representations of pain in the brain.
AB  - In this paper, the relationships between neural mechanisms of persistent pain and
      the neural representations of these conditions in the human and animal brain will
      be reviewed. Animal models of chronic pain, such as the sciatic nerve
      constrictive injuries, are accompanied by somatotopically organized increases in
      several pain-related areas of the brain. Recent human brain imaging studies
      utilizing functional magnetic resonance imaging and positron emission tomography
      have elucidated the cerebral representations of visceral and somatic
      hypersensitivity. Both forms of hypersensitivity are represented in similar brain
      regions that are activated during acute pain, yet have a more extensive or
      intense cerebral representation. This suggests that these somatic and visceral
      hyperalgesic states may be represented by increased activity in the same cerebral
      pathways and centers that are involved in nociceptive stimuli in normal
      individuals. Hyperalgesic states during clinically relevant pain are especially
      reflected in brain areas such as the anterior cingulate and prefrontal cortical
      regions.

PMID- 15251074
TI  - Growth hormone in musculoskeletal pain states.
AB  - Growth hormone is essential for normal linear growth and the attainment of an
      adult mature height. It also plays an important role in cartilage growth and the
      attainment of normal bone mass. There is only one rheumatic disorder, namely
      acromegaly, in which abnormalities of growth hormone production play a major
      etiologic role. However, there is increasing appreciation that suboptimal growth
      hormone secretion, leading to a state of adult growth hormone deficiency, may
      occur in the setting of chronic inflammatory disease, chronic corticosteroid use,
      and fibromyalgia. Therefore, the evaluation and effective management of growth
      hormone oversecretion and undersecretion is relevant to practicing
      rheumatologists.

PMID- 15251075
TI  - Pharmaceutical treatment options for fibromyalgia.
AB  - Fibromyalgia syndrome (FMS) is a chronic multisymptom illness characterized by
      widespread pain and associated with neuropsychological symptoms including
      fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. A
      discreet cause of FMS has not been identified. It is likely that multiple
      mechanisms give rise to symptom expression. Understanding specific etiologic
      factors and pathogenic mechanisms in individual patients will allow clinicians to
      determine treatments that are most effective for a given patient. Available
      evidence implicates the central nervous system as key in maintaining pain and
      other core symptoms of FMS. The approach to treatment of pain will typically
      address these central mechanisms. Nonpain symptoms may be treated by drugs
      affecting similar central neurochemicals. This paper will review the rationale
      for the different types of pharmaceutical treatments that may be useful for the
      treatment of FMS and issues regarding new drug development for this indication.

PMID- 15251076
TI  - Predictors of clinical pain intensity in patients with fibromyalgia syndrome.
AB  - Central changes in pain processing have been previously reported in patients with
      fibromyalgia syndrome. These changes include decreased thresholds to mechanical
      and thermal stimuli (allodynia) and central sensitization, both of which are
      fundamental to the generation of clinical pain. Therefore, psychophysical
      measures of central pain processing may be useful predictors of clinical pain
      intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia
      syndrome patients have shown statistically significant correlations of
      psychophysical test results with clinical pain intensity. The tests used to
      characterize this important relationship were dependent on spinal cord pain
      mechanisms and included temporal summation of pain or wind-up and wind-up after
      sensations. Particularly, the magnitude of wind-up after-sensations appeared to
      be one of the best predictors for clinical pain intensity of fibromyalgia
      syndrome patients (27%). Furthermore, the combination of tender point count,
      negative affect, and wind-up after-sensations accounted for approximately 50% of
      the variance in clinical pain intensity of fibromyalgia syndrome patients.
      Therefore, wind-up after-sensations, tender point count, and negative affect not
      only seem to represent relevant pain mechanisms but also strongly emphasize their
      importance for fibromyalgia syndrome pain.

PMID- 15251077
TI  - Comparison of methotrexate and cyclosporine therapy in psoriasis.

PMID- 15251078
TI  - Efalizumab therapy in plaque psoriasis.

PMID- 15251079
TI  - Treatment of psoriasis with intramuscular alefacept.

PMID- 15251080
TI  - Etanercept monotherapy in psoriasis.

PMID- 15251081
TI  - Tumor necrosis factor-alpha in psoriasis and psoriatic arthritis: a clinical,
      genetic, and histopathologic perspective.
AB  - The successful introduction of anti-tumor necrosis factor (TNF) therapies in
      psoriasis and psoriatic arthritis has sharpened considerable interest in this
      chronic and frequently disabling disease. Unlike the situation in rheumatoid
      arthritis, where anti-TNF therapies were introduced after years of painstaking
      research which confirmed a key proinflammatory role for TNF, the evidence for TNF
      having a key role in psoriatic arthritis has lagged behind. In this paper, the
      emerging immunohistochemical, genetic, and clinical literature relating to TNF's
      role in skin and joint manifestations of this disease is reviewed and areas for
      future research are suggested.

PMID- 15251082
TI  - Development of diagnostic criteria for psoriatic arthritis: methods and process.
AB  - Psoriatic arthritis is an inflammatory arthritis associated with psoriasis but
      this simple definition obscures the difficulty in defining the condition for
      epidemiologic purposes. Since the original description by Moll and Wright, a
      number of other classification criteria have been published. None of these have
      been fully evaluated and only one has been developed using patient derived data.
      Methodologic problems in developing classification criteria--their purpose,
      utility, and accuracy--are discussed in relation to a new International
      collaboration, the International Multicentre Validation of Diagnostic Criteria
      for Psoriatic Arthritis (CASPAR).

PMID- 15251083
TI  - Common clinical features and disease mechanisms of psoriasis and psoriatic
      arthritis.
AB  - Psoriasis and psoriatic arthritis are chronic inflammatory diseases that
      significantly affect patients' quality of life. Not only do these diseases impact
      patients' physical well-being, but also detrimentally affect their life socially
      and psychologically. There are many different patterns of skin and joint
      involvement. Understanding the pathogenesis of these diseases has evolved greatly
      in the past few decades. It is now understood that psoriasis and psoriatic
      arthritis are T cell mediated disorders. A number of proinflammatory cytokines
      have been suggested as playing a role in the disease mechanism, such as tumor
      necrosis factor-alpha and interferon-gamma. Other important factors proposed in
      the pathogenesis of these diseases include the role of genetics and environmental
      factors. New immunomodulating therapies, which are being developed as our
      understanding of the involvement of innate and adaptive immunity advances, will
      provide patients with safer, more effective, long-term, management options.

PMID- 15251084
TI  - Psoriasis: a complex clinical and genetic disorder.
AB  - Psoriasis is associated with arthritis in approximately 10% of patients. The skin
      disease and arthritis have a strong but complex genetic component. Several
      susceptibility loci have been reported including one major locus that maps very
      close to the human leukocyte antigen-C gene on chromosome 6p. No causative gene
      has so far been conclusively identified. A recent genetic analysis that only
      included patients with psoriatic arthritis revealed a highly significant
      susceptibility locus on chromosome 16q approximately 20 cM from the NOD2 gene
      that has been associated with Crohn's disease. This locus was barely detectable
      when the entire cohort of psoriasis patients was analyzed as a homogeneous
      entity. A further clinical stratification of psoriasis patients has revealed
      novel strongly suggestive loci and also increased the logarithm of the odds
      scores of some previously reported loci. It is concluded that a careful
      documentation of clinical features and phenotypic stratification may help to
      analyze complex genetic disorders.

PMID- 15251085
TI  - Magnetic resonance imaging of psoriatic arthritis: insight from traditional and
      three-dimensional analysis.
AB  - The magnetic resonance imaging (MRI) findings in psoriatic arthritis (PsA) are
      the same and at the same time different from those seen in other inflammatory
      arthritides. Synovial hypertrophy is seen on MRI in all arthritides. However, the
      location and extent of bone marrow edema in PsA is different from those seen in
      rheumatoid arthritis (RA) and osteoarthritis. Progression studies in PsA are hard
      to justify. However, treatment monitoring studies have given insight into the
      pattern of progression of the MRI findings and information regarding the
      mechanism of the effect of the drugs used for treatment. Three-dimensional image
      analysis tools provide volumetric information and information regarding the
      spatial and temporal relationship between different MRI findings. The three
      dimensional perfusion image analysis tool, which is used to evaluate the effect
      of antiangiogenic drugs in cancer treatment, can provide information regarding
      the disease mechanism when used in disease monitoring studies.

PMID- 15251087
TI  - Statins prevent strokes in high-risk patients.

PMID- 15251088
TI  - Antibiotics ineffective for prevention of recurrent MI.

PMID- 15251089
TI  - Disclosure of errors preferred by patients.

PMID- 15251090
TI  - Cephalosporins better for streptococcus infections in children.

PMID- 15251091
TI  - British Hypertension Society guidelines (BHS-IV).

PMID- 15251092
TI  - Tinnitus: questions to reveal the cause, answers to provide relief.

PMID- 15251093
TI  - Pigmented lesion on the ear.

PMID- 15251094
TI  - 3 regimens for alcohol withdrawal and detoxification.

PMID- 15251095
TI  - Clinical guidelines of depression: a qualitative study of GPs' views.
AB  - BACKGROUND: Clinical guidelines have become an increasingly familiar component of
      health care, although their passive dissemination does not ensure implementation.
      This study is concerned with general practitioners' (GPs) views of guideline
      implementation in general practice. It focuses specifically on their views about
      guidelines for the management of patients with depression. OBJECTIVE: To elicit
      and explore GPs' views about clinical guidelines for the management of
      depression, their use in practice, barriers to their use, and how best to
      implement guidelines. DESIGN: Qualitative study using in-depth interviews with a
      purposive sample of GPs. SETTING: General Practices across the Scottish Grampian
      region, and Northeast England. METHODS: Eleven GPs who had participated in a
      previous questionnaire based depression study were interviewed. Interviews were
      transcribed and analyzed using the "framework technique." RESULTS: Several
      participating GPs did not agree with recommendations of the current depression
      guidelines; some thought they were insufficiently flexible to use with the
      variety of patients they see. The volume of guidelines received, lack of time and
      resources (particularly mental health professionals for referrals) were seen as
      the main barriers to guideline use. CONCLUSIONS: A range of factors contributes
      to variability in compliance with guidelines for the management of depression.
      For guideline use to increase, GPs in this study said they would like to see more
      resources put in place; a reduction in the number of guidelines they receive;
      incorporation of guideline recommendations onto computer decision support
      systems; and regular audit and feedback to allow them to monitor their practice.

PMID- 15251096
TI  - Localized itching as a harbinger of breast cancer?

PMID- 15251097
TI  - HIV prevention enters a new era.

PMID- 15251098
TI  - The power of power.

PMID- 15251099
TI  - Clinical inquiries. Is an outpatient workup safe for patients with a transient
      ischemic attack?

PMID- 15251101
TI  - Clinical inquiries. Do statins reduce the risk of stroke?

PMID- 15251100
TI  - Clinical inquiries. Does combining aspirin and warfarin decrease the risk of
      stroke for patients with nonvalvular atrial fibrillation?

PMID- 15251102
TI  - Clinical inquiries. Other than anticoagulation, what is the best therapy for
      those with atrial fibrillation?

PMID- 15251103
TI  - Clinical inquiries. What is the best therapy for superficial thrombophlebitis?

PMID- 15251104
TI  - Clinical inquiries. Does moderate exercise prevent MI for patients with coronary
      heart disease?

PMID- 15251106
TI  - Adolescent sexual health.

PMID- 15251107
TI  - Oral contraceptive update: new agents and regimens.

PMID- 15251108
TI  - The menopausal transition: how does route of delivery affect the risk/benefit
      ratio of hormone therapy?

PMID- 15251109
TI  - After menopause: novel marker helps to identify women at risk for heart disease.

PMID- 15251110
TI  - Herpesviral Fcgamma receptors: culprits attenuating antiviral IgG?
AB  - Production of IgG in response to virus infection is central to antiviral immune
      effector functions and a hallmark of B cell memory. Antiviral antibodies (Abs)
      recognising viral glycoproteins or protein antigen displayed on the surface of
      virions or virus-infected cells are crucial in rendering the virus noninfectious
      and in eliminating viruses or infected cells, either acting alone or in
      conjunction with complement. In many instances, passive transfer of Abs is
      sufficient to protect from viral infection. Herpesviruses (HV) are equipped with
      a large array of immunomodulatory functions which increase the efficiency of
      infection by dampening the antiviral immunity. Members of the alpha- and beta
      subfamily of the Herpesviridae are distinct in encoding transmembrane
      glycoproteins which selectively bind IgG via its Fc domain. The Fc-binding
      proteins constitute viral Fcgamma receptors (vFcgammaRs) which are expressed on
      the cell surface of infected cells. Moreover, vFcgammaRs are abundantly
      incorporated into the envelope of virions. Despite their molecular and structural
      heterogeneity, the vFcgammaRs generally interfere with IgG-mediated effector
      functions like antibody (Ab)-dependent cellular cytolysis, complement activation
      and neutralisation of infectivity of virions. vFcgammaRs may thus contribute to
      the limited therapeutic potency of antiherpesviral IgG in clinical settings. A
      detailed molecular understanding of vFcgammaRs opens up the possibility to design
      recombinant IgG molecules resisting vFcgammaRs. Engineering IgG with a better
      antiviral efficiency represents a new therapeutic option against herpesviral
      diseases.

PMID- 15251111
TI  - Enhanced clearance of Escherichia coli and Staphylococcus aureus in mice treated
      with cyclophosphamide and lactoferrin.
AB  - Previous studies on cyclophosphamide (CP)-immunocompromised mice showed
      accelerated reconstitution of immune system function following oral treatment
      with lactoferrin (LF). The aim of this investigation was to evaluate the ability
      of mice, treated with a sublethal dose of CP and given LF, to combat bacterial
      infections. Mice were injected with a single, intraperitoneal dose of CP (350
      mg/kg body weight). One group of CP-treated mice was also given LF in drinking
      water (0.5% solution) for 14 days. Untreated and LF-treated mice served as
      controls. On day 15 following CP administration, mice were infected intravenously
      with 10(8) Escherichia coli or 5 x 10(7) Staphylococcus aureus. Twenty-four hours
      later, the number of colony-forming units (CFU) in spleens and livers were
      determined. Phenotypic analysis of blood leukocytes was determined, as well as
      the ability of splenic and peritoneal cells to produce IL-6 spontaneously and in
      the presence of lipopolysaccharide (LPS). Treatment with CP, or with CP and LF,
      led to profound reduction of E. coli CFU in the liver and the spleen; treatment
      with LF alone had significant inhibitory effects on organ enumerated CFU. S.
      aureus CFUs were also significantly reduced in spleens of mice treated with CP or
      CP/LF and, to a lesser degree, after LF alone. These effects were also
      significantly reduced in the livers. Analysis of blood cellular phenotype
      revealed total number of peripheral leukocytes was lower in the CP-treated group
      (52.6%) but not significantly different from control values in CP/LF and LF
      treated groups (90.7% and 104.6%, respectively). Conversely, percentage of blood
      neutrophils was markedly elevated in CP and CP/LF groups--62% and 42.5% vs. 18.4%
      in controls. These findings were accompanied by production of IL-6 by splenic and
      peritoneal cells which was significantly increased in CP- and CP/LF-treated
      groups. It was concluded that the increased clearance of bacteria in the organs
      of mice treated with CP and CP/LF may result from a rise in the number of
      neutrophils infiltrating the organs and contributing to accelerated clearance of
      bacteria. The study also suggests that the ability of cells from CP- and CP/LF
      treated mice to produce significantly more IL-6 may also contribute to increased
      resistance to infections. Lastly, together with our previous data, this study
      indicates that LF used to reconstitute the antigen-specific immune response in CP
      treated mice does not impair their resistance to infection.

PMID- 15251112
TI  - JP-8 jet fuel exposure induces inflammatory cytokines in rat skin.
AB  - The Department of Defense (DoD) has identified that one of the main complaints of
      personnel exposed to JP-8 jet fuel is irritant dermatitis. The purpose of this
      investigation is to describe the JP-8-induced inflammatory cytokine response in
      skin. JP-8 jet fuel or acetone control (300 microl) was applied to the denuded
      skin of rats once a day for 7 days. Skin samples from the exposed area were
      collected 2 and 24 h after the final exposure. Histological examination of skin
      biopsies showed neutrophilic inflammatory infiltrate. Reverse transcription
      polymerase chain reaction (RT-PCR) was performed utilizing skin total RNA to
      examine the expression of various inflammatory cytokines. The CXC chemokine
      GROalpha was significantly upregulated at both time points, whereas GRObeta was
      only increased 2 h post final exposure. The CC chemokines MCP-1, Mip-1alpha, and
      eotaxin were induced at both time points, whereas Mip-1beta was induced only 24 h
      post exposure. Interleukins-1beta and -6 (IL-1beta and IL-6) mRNAs were
      significantly induced at both time points, while TNFalpha was not significantly
      different from control. Enzyme-linked immunosorbent assay (ELISA) of skin protein
      confirmed that MCP-1, TNFalpha, and IL-1beta were modulated as indicated by PCR
      analysis. However, skin IL-6 protein content was not increased 2 h post exposure,
      whereas it was significantly upregulated by jet fuel after 24 h. Data from the
      present study indicate that repeated (7 days) JP-8 exposure induces numerous
      proinflammatory cytokines in skin. The increased expression of these cytokines
      and chemokines may lead to increased inflammatory infiltrate in exposed skin,
      resulting in JP-8-induced irritant dermatitis.

PMID- 15251113
TI  - Ciglitizone and 15d PGJ2 induce apoptosis in Jurkat and Raji cells.
AB  - Several studies have shown that PPARgamma agonists play a role in the regulation
      of lymphocytes function and apoptosis. However, the molecular mechanism(s)
      underlying the immunomodulatory effects of PPARgamma agonists are not defined
      yet. In this study, the effects of PPARgamma (15d PGJ2 and ciglitizone) ligands
      on proliferation, cytokine production and apoptosis of Jurkat and Raji cells
      (human T and B lymphocytes, respectively) were examined. Ciglitizone and 15d PGJ2
      presented antiproliferative and cytotoxic effects on Jurkat and Raji cells as
      shown by [14C]-thymidine incorporation and cell viability assay. In addition, 15d
      PGJ2 inhibited cytokine production (IL-2 in Jurkat cells and IL-10 in Raji
      cells). The mechanism whereby PPARgamma agonists induced cytotoxicity is via
      apoptosis as shown by DNA fragmentation, nuclear condensation and
      phosphatidylserine externalization. The induction of apoptosis by ciglitizone and
      15d PGJ2 on Jurkat and Raji cells may explain the suppression of cytokine
      production and the decrease in proliferation observed in both cell types. The
      apoptotic process was associated with a decrease in mitochondrial membrane
      potential and a marked down-regulation of the c-myc expression. These findings
      might play a key role in the apoptosis of T and B lymphocytes induced by
      PPARgamma agonists.

PMID- 15251114
TI  - Lactoferrin works as a new LPS-binding protein in inflammatory activation of
      macrophages.
AB  - Though lactoferrin (LF) is a glycoprotein that is involved in immunomodulation,
      its action mechanism has not been fully elucidated. Previous studies have
      suggested that lipopolysaccharide (LPS) activity is inhibited by direct binding
      between LPS and LF. However, here we show that when LPS and purified LF was
      mixed, and formed a complex (termed as LF-LPS), it was found to induce production
      of inflammatory mediators in macrophages to some extent, rather than inhibit LPS
      activity. Moreover, when macrophages were pretreated with LF-LPS, cells were
      rendered a tolerant state to LPS challenge. These macrophage-activating effects
      were mediated by Toll-like receptor 4 (TLR4)-NF-kappaB pathway. Comparative
      studies with C3H/HeN and C3H/HeJ mice demonstrated the strong dependency of the
      LF-LPS signal on TLR4. These findings suggest that the immunomodulatory
      properties of LF could be due, in part, to LPS binding.

PMID- 15251115
TI  - Clarithromycin and azithromycin induce apoptosis of activated lymphocytes via
      down-regulation of Bcl-xL.
AB  - To evaluate the anti-inflammatory action of macrolide antibiotics, we examined
      whether macrolide antibiotics could induce apoptosis of activated lymphocytes.
      The proportion of apoptotic cells was augmented by clarithromycin (CLR) and
      azithromycin (AZM) compared with control. There was no significant difference in
      Fas and Fas-ligand expression between the control and macrolide-treated groups.
      CLR and AZM inhibited the expression of Bcl-xL compared with that of control. Our
      results suggest that CLR and AZM enhance apoptosis of activated lymphocytes by
      down-regulation of Bcl-xL.

PMID- 15251116
TI  - Pharmacokinetics of fungal (1-3)-beta-D-glucans following intravenous
      administration in rats.
AB  - Glucans are microbial cell wall carbohydrates that are shed into the circulation
      of patients with infections. Glucans are immunomodulatory and have structures
      that are influenced by bacterial or fungal species and growth conditions. We
      developed a method to covalently label carbohydrates with a fluorophore on the
      reducing terminus, and used the method to study the pharmacokinetics following
      intravenous administration of three highly purified and characterized glucans
      (glucan phosphate, laminarin and scleroglucan) that varied according to molecular
      size, branching frequency and solution conformation. Elimination half-life was
      longer (3.8+/-0.8 vs. 2.6+/-0.2 and 3.1+/-0.6 h) and volume of distribution lower
      (350+/-88 ml/kg vs. 540+/-146 and 612+/-154 ml/kg) for glucan phosphate than for
      laminarin and scleroglucan. Clearance was lower for glucan phosphate (42+/-6
      ml/kg h) than for laminarin (103+/-17 ml/kg h) and scleroglucan (117+/-19 ml/kg
      h). Since plasma levels at steady state are inversely related to clearance, these
      differences suggest that pharmacokinetics could favor higher blood levels of
      glucans with certain physicochemical properties.

PMID- 15251117
TI  - Effect of Ginkgo biloba extract EGb 761 on the nonspecific and humoral immune
      responses in a hypothalamic-pituitary-adrenal axis activation model.
AB  - We evaluated the immune response of healthy control and stressed Wistar rats
      submitted to hypothalamic-pituitary-adrenal (HPA) axis activation. Rats were
      treated with Ginkgo biloba extract (EGb 761) orally (100 mg/kg per day for 7
      days). EGb 761 stimulated the digestion index of peritoneal and alveolar
      macrophages (PM and AM) of stressed rats. Likewise, the cellular immune response
      measured using the delayed-type hypersensitivity response to sheep red blood
      cells (SRBC) and the humoral immune response (measured through an anti-SRBC
      response), were also restored in stressed rats. Thus, this G. biloba extract
      possesses immunostimulatory activity in addition to its broad spectrum of
      pharmacological effects.

PMID- 15251118
TI  - Evaluation of immunotoxicity induced by propoxure in C57Bl/6 mice.
AB  - Insecticides are important candidates for immunotoxicology tests in order to
      assess the 'No Observable Adverse Effect Level' (NOAEL). Propoxure (PPX), as a
      carbamate household insecticide, has been used for several decades around the
      world in agriculture. However, there has been no clear investigation on its
      immunotoxic potentials. In this study, as Tier I of immunotoxicological screening
      tests, we examined the effects of subacute exposure to intraperitoneally (i.p.)
      administered PPX, at doses of 10, 2, and 0.2 mg/kg, on C57Bl/6 female mice. After
      28 days administration of PPX, the treated animals were sacrificed and peripheral
      blood samples were collected. Then spleen (SP), thymus (TM), and bone marrow were
      collected and weighed. Functional tests including SRBC-hemagglutination (HA),
      plaque-forming colony assay (PFC), and delayed type hypersensitivity (DTH)
      response to SRBCs were performed. Furthermore, spleen T-cell phenotype (CD4/CD8)
      was also determined. Results showed that high doses of PPX could not only produce
      histopathological changes in TM and SP but also suppress humoral response to
      antigen (SRBCs). PPX at medium doses (2 mg/kg) did not show histopathological
      changes in TM or SP but increased the humoral response to SRBCs, as identified by
      HA and PFC tests. PPX at low doses (0.2 mg/kg) did not produce any significant
      changes in humoral (PFC and HA) or cellular responses (DTH) of the immune system.
      It seems that PPX has no adverse effects on mice immune system at low doses of
      0.2 mg/kg/day, which is 10 times the PPX allowed daily intake (ADI) limit.

PMID- 15251119
TI  - Macrophage production of inflammatory mediators is potently inhibited by a
      butyric acid derivative demonstrated to inactivate antigen-stimulated T cells.
AB  - The butyric acid derivative, 2-(4-morpholynl) ethyl butyrate hydrochloride (MEB),
      has been reported to induce antigen-specific T cell unresponsiveness and to block
      T cell-mediated graft-versus-host disease. As a potential therapeutic agent, it
      was important to determine the effects of MEB on other cells that contribute to
      immunopathology. Accordingly, we tested the effects of MEB on macrophage
      functions. MEB did not affect macrophage viability, phagocytic activity, or the
      activation-induced up-regulation of molecules associated with antigen
      presentation: MHC-II, CD86, CD40, or ICAM-1. However, MEB potently inhibited
      activation-induced production of inflammatory mediators, including tumor necrosis
      factor-alpha (TNF-alpha), IL-6, chemokine CCL2 and nitric oxide (NO). MEB
      inhibited the induction of NO synthase (NOS2), which is necessary for inducible
      NO, and inhibited nuclear translocation of NFkappaB, suggesting that MEB
      interferes with the signaling pathway involved in NOS2 induction. Thus, while
      inducing specific T cell unresponsiveness, MEB also exerts anti-inflammatory
      activity by acting on macrophages to suppress production of cytokines and NO.

PMID- 15251122
TI  - Tumor necrosis factor-alpha in the pathogenesis and treatment of cancer.
AB  - The critical pathogenic role of tumor necrosis factor (TNF)alpha in inflammatory
      disorders such as rheumatoid arthritis and inflammatory bowel disease is well
      established. The role played by TNFalpha in both the treatment and pathogenesis
      of cancer remains less understood. Recent advances help to create a framework for
      understanding seemingly paradoxical effects of TNFalpha as both an anti-tumour
      agent and a mediator of tumour growth. High pharmacological doses of TNFalpha
      combined with chemotherapy can regress otherwise intractable tumours, and efforts
      continue to optimize delivery to avoid severe toxicities. Mounting evidence
      demonstrates that pathophysiological concentrations of endogenous TNFalpha act to
      promote tumour genesis and growth. The cellular and molecular pathways mediating
      these phenomena are starting to be clarified. Current data support the continued
      development of both TNFalpha and anti-TNFalpha therapy for clinical treatment of
      cancers in distinct settings.

PMID- 15251120
TI  - Effects of uridine, isomatitol and 4-thiouridine on in vitro cell adhesion and in
      vivo effects of 4-thiouridine in a lung inflammation model.
AB  - Since leukocyte adhesion to endothelial cells is crucial for extravasation of
      leukocytes to sites of inflammation, inhibition of cell-cell adhesion has been
      suggested as a means to achieve selective modulation of the immune system. We
      have, using a static in vitro adhesion assay involving adhesion of granulocytes
      to tumor necrosis factor alpha (TNFalpha)-stimulated human umbilical vein
      endothelial cells (HUVEC), found three substances--uridine, isomaltitol and 4
      thiouridine-that, independently and significantly, reduced leukocyte adhesion by
      approximately 30-65%. 4-Thiouridine was also tested in an in vivo model of
      Sephadex (SDX)-induced lung inflammation with Sprague-Dawley rats. Intratracheal
      instillation of Sephadex (5 mg/kg) alone resulted in a dramatic increase in lung
      edema and total leukocyte count after 24 h. A differential count of
      bronchoalveolar lavage (BAL) cells indicated an increased influx of macrophages,
      eosinophils and neutrophils. Co-administration of 4-thiouridine significantly
      reduced lung edema by 38%. There was also a significant reduction of the total
      leukocyte count by 58%. The differential leukocyte count indicated that
      eosinophil influx alone was reduced by 70%. After Sephadex challenge, we found
      elevated levels of TNFalpha--an important inflammatory mediator--in the
      bronchoalveolar lavage fluid (BALF). TNFalpha levels were significantly reduced
      by more than 80% by co-administration of 4-thoiuridine. These results suggest
      that uridine, isomaltitol and, especially, 4-thiouridine affect adhesion between
      leukocytes and activated endothelium, and warrant further in vitro and in vivo
      studies.

PMID- 15251123
TI  - The Fas signalling pathway and its role in the pathogenesis of cancer.
AB  - Tumor cells frequently exhibit de novo expression of Fas ligand (FasL/CD95L).
      Coupled with resistance to Fas-mediated apoptosis, FasL expression enables many
      cancers to deliver a pre-emptive strike or 'counterattack' against the immune
      system. New studies also indicate that FasL expression on tumor cells could
      confer a double advantage to these cells by stimulating their own proliferation.
      However, pro-inflammatory effects of FasL have also been observed. New findings
      are beginning to reconcile the paradoxical effects of FasL, with the clinical
      significance of the Fas counterattack only beginning to emerge.

PMID- 15251124
TI  - Signaling through death receptors in cancer therapy.
AB  - Apoptosis--the cell's intrinsic program for death--plays a central role in
      regulation of tissue homeostasis. Accordingly, tipping the balance between cell
      death and proliferation in favor of cell survival can result in tumor formation.
      Also, killing of cancer cells by cytotoxic therapies (e.g. chemotherapy, gamma
      irradiation, immunotherapy or suicide gene therapy) largely depends on intact
      apoptosis programs in cancer cells. To this end, it is implied that death
      receptor signaling contributes to the efficacy of cancer therapy. Failure to
      undergo apoptosis in response to anticancer therapy can therefore result in
      resistance. Thus, insights into the mechanisms regulating apoptosis in response
      to anticancer therapy and the ways in which cancer cells evade apoptosis might
      provide new opportunities for drug development.

PMID- 15251125
TI  - Targeting death receptors in cancer with Apo2L/TRAIL.
AB  - Unlike conventional cancer therapeutics, death receptor ligands trigger tumor
      cell apoptosis independently of the p53 tumor suppressor gene, which frequently
      is inactivated in cancer. The death receptor ligand Apo2 ligand/tumor necrosis
      factor-related apoptosis-inducing ligand (Apo2L/TRAIL) offers promising
      therapeutic potential based on its ability to induce apoptosis in various cancer
      cell lines with little toxicity toward normal cells. Moreover, Apo2L/TRAIL
      displays single-agent activity and cooperates with chemotherapy or radiotherapy
      in a variety of tumor xenograft mouse models. Thus, Apo2L/TRAIL might be
      effective against tumors that have acquired resistance to conventional therapy,
      and could augment the efficacy of current treatment in a wide spectrum of
      cancers.

PMID- 15251126
TI  - Evidence of a role for RANKL in the development of myeloma bone disease.
AB  - Multiple myeloma is associated with the development of a devastating bone disease
      mediated by increased osteoclastic activity. The ligand for receptor activator of
      nuclear factor-kappaB (RANKL) plays a critical role in normal osteoclast biology
      and is abnormally regulated in myeloma. Targeting this system with recombinant
      decoy receptor, osteoprotegerin, or soluble forms of the receptor activator of
      nuclear factor-kappaB is able to prevent myeloma bone disease in pre-clinical
      models. Intriguingly, inhibiting osteoclast formation and bone resorption, and
      altering the bone marrow microenvironment, results in an indirect anti-myeloma
      effect.

PMID- 15251128
TI  - The role of CD30 in the pathogenesis of haematopoietic malignancies.
AB  - CD30, a member of the tumour necrosis factor receptor superfamily, is
      overexpressed by malignant cells of Hodgkin's lymphoma and by anaplastic large
      cell lymphoma. CD30 overexpression has been attributed, at least in part, to
      constitutive expression of JunB, a transcription factor belonging to the AP-1
      family that binds to the CD30 promoter. Overexpression of CD30 in Hodgkin's
      lymphoma cells is thought to result in ligand-independent signaling, leading to
      activation of nuclear factor-kappaB and survival of the malignant cells. In
      anaplastic large cell lymphoma, CD30 triggering induces growth arrest and, under
      certain circumstances, cell death. Finally, transmembrane signalling by CD30
      might be regulated by a soluble form of CD30 that is released by proteolytic
      cleavage of membrane-anchored CD30.

PMID- 15251127
TI  - The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers.
AB  - Signaling through the B cell antigen receptor promotes activation and survival of
      mature B cells. B cell-activating factor belonging to the tumor necrosis factor
      family (BAFF) is another critical survival factor for B cells, and is also
      necessary for B cell maturation. Abnormal production of BAFF disturbs immune
      tolerance by allowing the survival of autoreactive B cells, thus triggering
      autoimmune disorders. BAFF can also have an important impact on B cell
      malignancies. In contrast to normal B cells, malignant B cells show uncontrolled
      cell proliferation. BAFF levels are elevated in the serum of patients with
      systemic autoimmune diseases, and, importantly, in patients with B-lymphoid
      malignancies. Furthermore, BAFF is produced by malignant B cells and acts as an
      essential autocrine survival factor. The strong dependence of certain lymphoid
      cancer cells on BAFF might be a point of vulnerability, which offers exciting new
      therapeutic possibilities.

PMID- 15251129
TI  - The role of the CD40 pathway in the pathogenesis and treatment of cancer.
AB  - CD40 is a tumour necrosis factor receptor family member that is overexpressed in
      a broad range of leukaemias, lymphomas and carcinomas, and could contribute to
      their development. Recent experimental and clinical observations suggest that the
      CD40 pathway can be exploited for the treatment of malignancy. The mechanisms by
      which CD40 activation exerts anti-tumour effects include inhibition of tumour
      cell proliferation, sensitisation to other anti-cancer agents, including
      cytotoxic drugs, upregulation of immune processing and presentation within the
      malignant cells, and stimulation of anti-tumour immune responses via activation
      of dendritic cells. Thus, the CD40 pathway provides an opportunity to muster
      different anti-cancer approaches in one therapy, and offers an attractive option
      for future clinical trials.

PMID- 15251130
TI  - New approaches to therapeutic immunomodulation for immune-mediated inflammatory
      disorders.

PMID- 15251131
TI  - The p38 MAP kinase pathway as a therapeutic target in inflammatory disease.
AB  - The p38 MAPK signalling pathway plays an important role in inflammation and other
      physiological processes. Specific inhibitors of p38 alpha and beta MAPK block
      production of the major inflammatory cytokines (i.e. tumour necrosis factor-alpha
      and interleukin-1) and other proteins (e.g. cyclooxygenase-2), and are anti
      inflammatory in animal models of disease. A major function of the pathway is post
      transcriptional control of inflammatory gene expression. Many of the mRNAs are
      unstable (or untranslatable) because of AU-rich elements in the 3'untranslated
      region. Signalling in the p38 pathway counteracts these and stabilizes the mRNAs
      by preventing their otherwise rapid de-adenylation.

PMID- 15251132
TI  - Therapeutic strategies to reduce IL-1 activity in treating local and systemic
      inflammation.
AB  - All biological agents currently used for reducing TNFalpha activity in disease
      are neutralization strategies; however, there are several strategies for reducing
      interleukin (IL)-1 activities: the IL-1 receptor antagonist (IL-1Ra), anti-IL
      1beta monoclonal antibodies, the IL-1 Trap, IL-1 receptor type I antibodies,
      antibodies to the IL-1 receptor accessory chain and inhibitors of IL-1beta
      converting enzyme, now termed caspase-1. In fact, caspase-1 inhibitors are the
      first orally active agents that target cytokines, as these inhibitors prevent the
      processing and release of active forms for IL-1beta and IL-18, which is a member
      of the IL-1 family. The IL-1 Trap is a new concept in using soluble forms of
      cytokine receptors to bind and neutralize a specific cytokine. The Trap takes
      advantage of the high affinity of the two signaling chains of the cell surface IL
      1 receptor linked by the Fc portion of IgG1. The IL-1Ra is currently approved to
      treat rheumatoid arthritis; in over 75 000 patients, the IL-1Ra has provided
      insights into the role of IL-1 in local and systemic inflammation, as well as the
      safety of long-term reduction of IL-1 activity.

PMID- 15251133
TI  - Inhibition of IL-6 for the treatment of inflammatory diseases.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine with various biological
      activities. Deregulated overproduction of IL-6 has been found to play
      pathological roles in chronic inflammatory diseases such as rheumatoid arthritis,
      Castleman's disease, juvenile idiopathic arthritis and Crohn's disease. Humanized
      anti-IL-6 receptor antibody has been developed as a therapeutic agent for these
      diseases, and therapeutic benefits have been revealed in clinical studies.

PMID- 15251134
TI  - Interleukin-15: a new cytokine target for the treatment of inflammatory diseases.
AB  - Interleukin (IL)-15 is a pleiotropic pro-inflammatory cytokine that is expressed
      in several inflammatory disorders, including rheumatoid arthritis, psoriasis and
      pulmonary inflammatory diseases. IL-15 promotes activation of T cells,
      neutrophils and macrophages, and is critical to dendritic cell function in
      several model systems. Recent emerging data suggest that IL-15 may serve as a
      useful therapeutic target across a range of disease states. Advances in the past
      year highlight the beneficial effect of IL-15 neutralisation in models of
      psoriasis and diabetes. Further evidence for IL-15 expression and effector
      function has emerged across a range of rheumatic disorders, including juvenile
      inflammatory arthritis, rheumatoid arthritis and Kawasaki disease. These data
      hold promise for therapeutic targeting in ongoing human studies and those in the
      near future.

PMID- 15251135
TI  - Anti B cell therapy (rituximab) in the treatment of autoimmune diseases.
AB  - B cells play an important role in the pathogenesis of many autoimmune diseases.
      Selective targeting of these cells has been recently achieved using a chimeric
      monoclonal antibody against the pan B cell surface marker CD20 (rituximab). This
      antibody was originally developed for the treatment of non-Hodgkin's lymphoma. It
      was found to be effective, well tolerated and had a very good safety profile.
      Recent studies have demonstrated the efficacy of rituximab in several refractory
      autoimmune disorders including rheumatoid arthritis, systemic lupus
      erythematosus, immune thrombocytopenic purpura, chronic cold agglutinin disease,
      IgM-mediated neuropathies and mixed cryoglobulinemia.

PMID- 15251136
TI  - Anti-CD3 antibodies: towards clinical antigen-specific immunomodulation.
AB  - Current therapeutic approaches in transplantation and autoimmunity are
      essentially focused on immunosuppression, which is non-specific (i.e. unrelated
      to the antigens involved). The major drawback is their relative ineffectiveness
      in the long term, with the likely risk of recurrence of the pathogenic immune
      process once the drug is withdrawn necessitating indefinite drug administration;
      this has attendant problems of recurrent infections and drug toxicity. Instead,
      CD3-specific monoclonal antibodies possess the unique capacity to induce
      immunological tolerance: an antigen-specific unresponsiveness in the absence of
      long-term generalised immunosuppression, as is well-established in experimental
      models. Clinical application using humanised non-mitogenic CD3-specific
      antibodies is presently underway. The future challenge will be to define the
      modalities allowing the widespread application of this strategy through a better
      understanding of the underlying immune mechanisms.

PMID- 15251137
TI  - Regulatory T cells.
AB  - Regulatory T (TR) cells are a subset of T cells that function to control immune
      responses. Different populations of TR cells have been described, including
      thymically derived CD4(+)CD25+ TR cells and Tr1 cells induced in the periphery
      through exposure to antigen. A transcription factor, Foxp3, has been identified
      that is essential for CD4(+)CD25+ TR cell development and function. There is now
      evidence that transforming growth factor-beta might play a role in this pathway.
      CD4(+)CD25+ TR cells proliferate extensively in vivo in an antigen-specific
      manner, and can respond to both self and foreign peptides. By suppressing
      excessive immune responses, TR cells play a key role in the maintenance of self
      tolerance, thus preventing autoimmune disease, as well as inhibiting harmful
      inflammatory diseases such as asthma and inflammatory bowel disease.

PMID- 15251138
TI  - Negative regulation of T cell receptor signals.
AB  - T cells undergo clonal expansion upon encountering cognate antigen in peripheral
      lymphoid tissues. They require signals through both the T cell receptor and the
      costimulatory receptor CD28 for this process to occur. In the absence of CD28
      stimulation, T cell receptor signals are repressed by the ubiquitin ligase Cbl-b,
      which negatively regulates the activity of the downstream effectors PI3Kp85 and
      Vav1. CD28 signals overcome this repression, at least in part, by ubiquitinating
      and degrading Cbl-b itself. CD28 signals induce clustering of cell-surface
      receptors, cell division and optimal interleukin-2 production. The Cbl-b/CD28
      regulatory axis has profound implications for pathological conditions ranging
      from autoimmunity to cancer.

PMID- 15251139
TI  - Therapeutic inhibition of leukocyte recruitment in inflammatory diseases.
AB  - The ingress of leukocytes into sites of inflammation is crucial for the
      pathogenesis of arthritis and other inflammatory conditions. Chemokines, their
      receptors and cellular adhesion molecules (CAMs) are involved in this process.
      Here, the roles of the most relevant chemokines, chemokine receptors and CAMs are
      briefly reviewed. There have been several attempts to target chemokine- and CAM
      mediated pathways in preclinical studies using animal models of arthritis, and in
      a limited number of human studies. In this review, the most recent advances in
      anti-chemokine and anti-adhesion therapeutic strategies are summarized.

PMID- 15251140
TI  - Neonatal autopsy.

PMID- 15251141
TI  - Clinical aspects of neonatal death and autopsy.
AB  - An autopsy carried out by a trained perinatal pathologist can provide parents and
      professionals with new information about the cause of a baby's death. It is
      extremely stressful for parents to be asked for autopsy authorisation. The
      request is also very demanding for the staff. The rates of neonatal autopsy have
      been declining since 1990 and, almost certainly, the adverse publicity
      surrounding the Alder Hey enquiry precipitated a further fall in authorisation
      rates. Only a re-establishment of trust between parents and professionals can
      reverse this trend. This trust is founded on excellent perinatal communication
      and clinical care. The child's death must be managed in the most empathetic way,
      with an understanding of bereavement and the grief support required. If the
      parents and professionals work together as a team, the parents should sense the
      commitment of staff to their family. They may then be more likely to understand
      the importance of autopsy and to provide authorisation.

PMID- 15251142
TI  - Placental vascular development and neonatal outcome.
AB  - The juxtaposition of the maternal and fetal circulations allows optimal
      physiological exchange between mother and fetus. Extravillous trophoblast
      infiltrating into the placental bed transforms the small calibre spiral arteries
      into large calibre uteroplacental arteries. The absence of these physiological
      changes, coupled with other lesions such as acute atherosis, results in a reduced
      uteroplacental blood flow, as seen in pre-eclampsia, intrauterine growth
      restriction and preterm delivery. A failure to elaborate the placental vascular
      tree can result in impaired flow through the fetal placental circulation.
      Placental vascular malformations, such as placental mesenchymal dysplasia and the
      commoner chorangioma, can lead to neonatal complications. Fetal thrombotic
      vasculopathy, commonly associated with thrombophilia, may be a cause of
      neurological deficit in childhood.

PMID- 15251143
TI  - Placental inflammation.
AB  - Placental inflammatory disorders represent a diverse and important category of
      pathological processes leading to fetal and neonatal morbidity and mortality.
      These processes can be divided into two broad subcategories, those caused by
      micro-organisms and those caused by host immune responses to non-replicating
      antigens. The mechanisms by which these inflammatory processes cause death and
      disability are diverse and can be separated into four distinct classes: placental
      damage with loss of function, induction of premature labour and subsequent
      preterm birth, release of inflammatory mediators leading to fetal organ damage
      and transplacental infection of the fetus. Each specific inflammatory process can
      be modulated by properties of the specific organism, the route and timing of
      infection and variations in the host's genetic background and immune
      responsiveness. All of these factors combine to produce specific patterns of
      placental pathology that can be used to guide treatment, predict complications
      and explain adverse outcome.

PMID- 15251144
TI  - Perimortem laboratory investigation of genetic metabolic disorders.
AB  - Over 400 rare, biochemically diverse genetic metabolic disorders (inborn errors
      of metabolism) have been described and the list is growing by the month. Although
      recent advances in the diagnosis and treatment of these disorders have
      substantially improved the prognosis for many of them, including those presenting
      in the neonatal period, a proportion of affected individuals die before the
      diagnosis can be confirmed and, in some cases, before the diagnosis is even
      considered. This review will provide an outline of the range of clinical
      presentations seen in neonates with genetic metabolic disorders and provide a
      practical approach for rapid biochemical screening for these disorders. In
      addition, suggested guidelines are given for the collection of relevant samples
      in the perimortem period, the aim being to maximize the chance of identifying any
      underlying genetic metabolic disorder.

PMID- 15251145
TI  - Non-iatrogenic pathology of the preterm infant.
AB  - Non-iatrogenic anatomical findings at autopsy provide insight into preterm infant
      physiology. The different patterns of lipid accumulation in the adrenal may
      correspond to long-term differences in stress response. Cardiac papillary muscle
      infarction occurs with asphyxia or shock and can explain myocardial dysfunction.
      Underdevelopment of preterm kidneys may correlate with susceptibility to renal
      disease and hypertension in adult life. Immaturity of the lung or immature
      responses to inflammation, rather than high oxygen concentrations or high
      ventilation pressures, may underlie chronic lung disease in premature infants.
      Hepatic extramedullary haematopoiesis is normal but, if excessive or abnormally
      persistent, can be an indicator of fetal disease. Hypertrophic somatostatin islet
      cells found with intra-uterine growth retardation may correlate with low serum
      insulin. Thymic involution may mark the degree of stress. Small thyroglobulin
      stores may limit the premature neonate's initiation of thermogenesis.

PMID- 15251146
TI  - Postmortem findings in term neonates.
AB  - Neonatal deaths in infants born at term are relatively rare in the USA, occurring
      in 0.9/1000 live births. Congenital malformations, perinatal asphyxia, infections
      and inborn errors of metabolism are the leading causes. Chromosomal malformation
      syndromes, congenital heart disease, pulmonary hypoplasia and severe neural tube
      defects comprise the majority of lethal malformations. Several skeletal
      dysplasias are lethal in the newborn infant. Group B Streptococcus still plays a
      major role in neonatal mortality while deaths due to other infectious agents have
      decreased. Hypoxic ischaemic encephalopathy is a significant cause of neonatal
      death. Inborn errors of metabolism have variable presentations but some, such as
      the fatty acid oxidation disorders, may present in neonates and cause sudden
      death.

PMID- 15251147
TI  - Iatrogenic damage in the neonatal period.
AB  - Iatrogenic damage from a therapeutic procedure in the neonatal period can have
      serious consequences. Although most side effects are minor, some may result in a
      major handicap or death of the infant. The development of new therapeutic
      strategies may result in not previously observed combinations of pathology. This
      review focuses on iatrogenic damage occurring in several organs and after several
      different therapeutic interventions. Special attention is given to pulmonary and
      gastrointestinal damage and iatrogenic damage as a result of systemic treatments.
      Valuable information and early detection of serious side effects is only possible
      when the pathologist is very well informed about the therapeutic interventions
      used, all medical devices are left in situ and a thorough autopsy is performed as
      completely as is permitted. However, the decline in autopsy rates could make it
      more difficult to determine the incidence of iatrogenic lesions.

PMID- 15251149
TI  - The value of autopsy in determining the cause of failure to respond to
      resuscitation at birth.
AB  - Autopsy is invaluable in identifying the causes of severe depression and very low
      Apgar score after birth and in assessing contributory conditions. Brain scans are
      increasingly used in the care of neonates who fail to respond to resuscitation at
      birth but their interpretation depends on the information gained from sound
      neuropathological studies. Asphyxia, both acute intrapartum asphyxia and chronic
      asphyxia, is an important cause of low Apgar scores. The gestational age and the
      nature of the asphyxial insult both have a profound influence on the ultimate
      pattern of injury. Asphyxia in the preterm brain tends to damage preferentially
      the white matter but some white matter damage is also seen in many infants who
      have an hypoxia-ischaemic insult at term though the predominant site of injury is
      to the central grey matter. The nature of the cellular damage and reactive change
      seen at autopsy is described. There is an association between low Apgar scores
      and intrauterine exposure to infection and maternal pyrexia. Detailed autopsy
      examination should include the search for infection. The placenta, cord and
      membranes should be examined in view of the mounting evidence of the association
      between intrauterine infection of the placenta and fetal membranes and prenatal
      brain damage. Additionally, the presence of placental thrombosis and infarction
      should be sought in relation to focal and global injury in the full term infant.
      Acquired prepartum lesions rarely cause the infant to present with a low Apgar
      score. The exception to this is severe damage to the brainstem and basal ganglia.
      Traumatic injury to the brain is now much less common than in previous decades.
      Subdural haemorrhage occurs more frequently than intraventricular or subarachnoid
      haemorrhage. Instrumental and assisted deliveries are associated with an
      increased incidence of subdural haemorrhage though these rarely cause significant
      long term damage. Careful autopsy, particularly of the neck and paravertebral
      tissues, spinal cord, brainstem and nerve roots is important where trauma is
      suspected. Tearing of nerve roots or fibre bundles in the spinal cord is readily
      demonstrated under the microscope using immunocytochemistry to beta-amyloid
      precursor protein. Disorders of the spinal cord, peripheral nerve and muscle as
      well as some metabolic diseases may cause a baby to be both floppy and weak.
      Metabolic disease, including peroxisomal disorders, non-ketotic hyperglycinaemia,
      lipid and glycogen storage disorders and mitochondrial diseases may cause
      profound hypotonia and respiratory failure at birth or shortly afterwards.

PMID- 15251148
TI  - Pulmonary pathology.
AB  - Common causes of neonatal respiratory distress include meconium aspiration,
      pneumonia, persistent pulmonary hypertension of the newborn, pneumothorax and
      cystic adenomatoid malformation. Genomics and proteomics have enabled the recent
      recognition of several additional disorders that lead to neonatal death from
      respiratory disease. These are broadly classified as disorders of lung
      homeostasis and have pathological features of proteinosis, interstitial
      pneumonitis or lipidosis. These pathological changes result from inherited
      disorders of surfactant proteins or granulocyte-macrophage colony stimulating
      factor. Abnormal lung vascular development is the basis for another cause of
      fatal neonatal respiratory distress, alveolar capillary dysplasia with or without
      associated misalignment of veins. Diagnosis of these genetically transmitted
      disorders is important because of the serious implications for future siblings.
      There is also a critical need for establishing an archival tissue bank to permit
      future molecular biological studies.

PMID- 15251150
TI  - Magnetic resonance imaging: an alternative to autopsy in neonatal death?
AB  - Magnetic resonance imaging (MRI) represents a non-invasive alternative to full
      autopsy in neonatal death if parents refuse classical full autopsy. MRI offers
      high resolution images of the entire neonate without disrupting the integrity of
      the child. Neonatal malformations or pathologies that are responsible for the
      death of the neonate can be identified. A major disadvantage of MR-autopsy is the
      lack of tissue sampling. Chromosomal, histological or microbiological analyses
      are consequently missing. MR-autopsy has proven to be especially helpful in the
      evaluation of the central nervous system but is limited in complex cardiac
      malformations. The limitations and possibilities of MR-autopsy are discussed.

PMID- 15251151
TI  - Use of imaging to detect recurrent cancer: how far should we go?

PMID- 15251152
TI  - Changing concepts in the pathological basis of soft tissue and bone sarcoma
      treatment.
AB  - Though soft tissue sarcomas are rare considerable progress has been made in the
      clinical and biological understanding of these neoplasms. This has led to the
      launch of a new WHO classification of soft tissue tumours in 2002, which
      integrate morphological data with tumour specific (cyto-) genetics. Moreover
      worldwide consensus has grown how to predict clinical behaviour based on a
      specific grading system and which specific types of tumours seem not to obey
      these rules. As a consequence entry criteria for multi-institute prospective
      trials have changed over the last few years. The recent identification of tumour
      specific drug targets by immunohistochemistry has had impact on specimen
      requirements and handling as well as laboratory standards. These changes in
      concepts, classification, and processing of soft tissue sarcomas have had impact
      on patient selection and treatment and formats of multi-institute trials.

PMID- 15251153
TI  - Follicular-cell derived thyroid cancer in children.
AB  - Thyroid carcinoma is a rare disease in children, and is mostly of the papillary
      histological type. It is often extended at presentation with frequent lymph node
      metastases. Treatment includes surgery (total thyroidectomy and lymph node
      dissection) and radioiodine therapy in case of extensive disease. Life long
      thyroxine treatment is given to all patients and when carefully controlled is
      devoided of adverse effects. Long term prognosis is favorable, but a few deaths
      have been reported some decades after initial treatment. Adverse prognostic
      indicators are younger age at discovery and presence of distant metastases.

PMID- 15251154
TI  - Tumour-associated macrophages as a prototypic type II polarised phagocyte
      population: role in tumour progression.
AB  - Macrophages are versatile, plastic cells which respond to micro-environmental
      signals with distinct functional programmes. In the tumour microenvironment,
      tumour-associated macrophages (TAM) polarise towards a type II phenotype,
      oriented to the promotion of tissue remodelling and repair. As polarised type II
      macrophages, TAM are a key component of the inflammatory circuits that promote
      tumour progression.

PMID- 15251155
TI  - Double-reading of plain radiographs--no benefit with regard to earliness of
      diagnosis of cancer recurrence: a randomised follow-up study.
AB  - The aim of this study was to estimate the effect of the radiologist's
      interpretation of plain radiographs on the earliness of diagnosis of cancer
      recurrences. Data consisted of patients who had undergone primary treatment and
      were resident in the Tampere University Hospital Area in Finland during 1991
      1997. Consecutive patients were randomised in a double-reading arm (an oncologist
      and a radiologist independently interpreting radiographs), and in a single
      reading arm (interpretation by an oncologist only; if necessary, a radiologist's
      clinical report was obtained following a separate request). The time of diagnosis
      of recurrence and death were estimated by the cumulative probabilities of
      actuarial method with the Wilcoxon (Gehan) test. There were 869 eligible
      participants, mostly breast cancer patients (n = 516). In total, 227 recurrences
      were diagnosed, and of these 55 on plain radiographs, which is 24.2% of the total
      number of recurrences. There was no statistically significant difference between
      the arms in the number of recurrences (P = 0.85) or in the time of detecting the
      recurrence (P = 0.64). Altogether, 225 (25.9%) died from cancer and 38 (4.4%)
      from other causes. There was no statistically significant difference (P = 0.34)
      in survival between the two arms during the follow-up to 5 years. Double-reading
      of plain radiographs does not offer any extra benefit for the detection of
      recurrences or for patient's survival compared with single-reading.

PMID- 15251156
TI  - Late toxicity following conventional radiotherapy for prostate cancer: analysis
      of the EORTC trial 22863.
AB  - Late toxicity and other serious adverse events (SAE) were analysed in the
      European Organisation for Research and Treatment of Cancer (EORTC) trial 22863.
      The study evaluated the value of adjuvant endocrine treatment for locally
      advanced prostate cancer treated with radiotherapy. From 1987 to 1995, 415
      patients were randomised. There was long-term toxicity information for 377
      patients (91%). Median age was 70 years (range 50-80 years). Median follow-up for
      late toxicity was 42 months (range 3-136 months). Toxicity was graded according
      to a modified Radiotherapy and Oncology Group (RTOG) scale. Other late SAE, that
      was not classified as severe treatment toxicity, but were still life-threatening,
      were also assessed. There were 72 patients with grade 2, 10 patients with grade 3
      and 4 patients with grade 4 toxicity. There were 20 patients with other late SAE,
      who were grouped according to their relationship to treatment; likely related (n
      = 1), unrelated (n = 7) and not assessable (n = 12). Although four treatment
      related deaths (1%) occurred, grade 3 or 4 late complications were less than 5%.

PMID- 15251157
TI  - Salvage chemotherapy with temozolomide in primary CNS lymphomas: preliminary
      results of a phase II trial.
AB  - Temozolomide is a well-tolerated alkylating agent, that is able to permeate the
      blood-brain barrier (BBB), and has additive cytotoxicity when given with
      radiotherapy (RT). A phase II trial assessing temozolomide 150 mg/m(2)/day, for 5
      days every 28 days in primary central nervous system (CNS) lymphoma (PCNSL)
      patients with negative human immunodeficiency virus (HIV) serology, Eastern
      Cooperative Oncology Group (ECOG) performance status (PS)<4, previously treated
      with high-dose methotrexate-containing (HD-MTX) chemotherapy and/or RT was
      started. Twenty-three patients were enrolled. Median age was 60 years. Five
      complete remissions (median duration 6+ months; range 2-36 months), one partial
      response, four stable disease (median duration 7.2 months, range 2-16.5 months),
      and 13 progressions were observed. No major toxicities were observed, apart grade
      3 vomiting in a single cycle. Main grade 1-2 toxicities were: 15% nausea, 6%
      vomiting, 9% fatigue and 9% neurological symptoms. This is the first prospective
      trial assessing single-agent activity in PCNSL at failure. Although some patients
      had a poor PS and had been heavily pre-treated, temozolomide yielded 26%
      objective responses and was well tolerated without any major toxicity.

PMID- 15251158
TI  - Fatigue and psychological distress--exploring the relationship in women treated
      for breast cancer.
AB  - Disabling fatigue and psychological symptoms of depression or anxiety are
      commonly reported by women with treated breast cancer. However, most instruments
      designed to assess fatigue do not assess concurrent psychological symptoms. This
      study compared the characteristics of two conceptually different, self-report
      instruments assessing fatigue to determine the extent to which common
      psychological symptoms co-exist with the symptom of fatigue in women treated for
      breast cancer. Women attending an oncology day-care facility for adjuvant
      treatment of breast cancer or ongoing surveillance post-treatment, completed two
      self-report questionnaires. The Somatic and Psychological Health REport-34 items
      (SPHERE) and the Functional Assessment of Cancer Therapy-Fatigue (FACT-F subscale
      13 items). One hundred and nine women (mean age 52.8 years) completed both
      questionnaires and total scores on both fatigue assessment scales, FACT-F and
      SOMA-6, were highly correlated (r = 0.72, P < 0.001). Using the SPHERE case
      criteria, prolonged fatigue (37% [40/109]) and psychological distress 31%
      (34/109) were common in women treated for breast cancer. However, those who
      reported fatigue were much more likely to also report psychological symptoms
      (22/40 vs. 12/69, X(2) = 16.7: degrees of freedom (df)=1; P < 0.001) and the
      levels of fatigue on the FACT-F were not significantly different between those
      who reported "fatigue only" and those who reported "psychological distress only"
      (18.8 vs. 17.8, P = 0.79). Thus the recent emphasis on recording fatigue during
      and following treatments for cancer needs to be accompanied by concurrent
      measurement of psychological symptoms.

PMID- 15251159
TI  - Quality of life and stress response symptoms in long-term and recent spouses of
      testicular cancer survivors.
AB  - The aim of this study was to gain insight into the quality of life (QoL) and
      stress response of female spouses of men cured of testicular cancer in the long
      term. Time since treatment completion varied from 0.5 to 23.8 years. Two hundred
      and fifty nine testicular cancer survivors and their spouses completed the Dutch
      version of the MOS Short Form (SF)-36 and the Impact of Event Scale. QoL data
      from a reference group of women were used for comparison. Spouses who had
      relationship with the testicular cancer survivor before the diagnosis (spouses
      during testicular cancer) had better functioning scores than the reference group,
      especially with respect to the physical QoL domains. Spouses who had started a
      relationship after treatment (spouses after testicular cancer) experienced more
      problems with psychological QoL domains than spouses during testicular cancer and
      than the reference group. The stress response of spouses during testicular cancer
      was related to that of the testicular cancer survivors and to the extent of
      treatment they had received. Although stress response levels were low, spouses
      during testicular cancer reported more stress response than the testicular cancer
      survivors. Time since completion of treatment did not affect QoL or stress
      response. This study showed that spouses during testicular cancer had a good QoL
      and little stress response. Functioning of spouses after testicular cancer was
      poorer with respect to various QoL domains, particularly the psychological
      measures.

PMID- 15251160
TI  - Improved quality of life after long-term treatment with the bisphosphonate
      ibandronate in patients with metastatic bone disease due to breast cancer.
AB  - Bone metastases occur in most women with advanced breast cancer and can lead to
      considerable morbidity and a rapid deterioration in the patient's quality of
      life. It was the aim of the present study to assess changes in quality of life
      and bone pain due to intravenous (i.v.) ibandronate, a potent third-generation
      bisphosphonate. In a phase III randomised, double-blind, placebo-controlled trial
      in patients with bone metastases due to breast cancer, 466 women were randomised
      to receive placebo, 2 mg ibandronate or 6 mg ibandronate for up to 96 weeks.
      Treatment was administered i.v. at 3- or 4-weekly intervals. Clinical endpoints
      included the incidence of adverse events, quality of life (assessed using the
      European Organisation for the Research and Treatment of Cancer (EORTC) Quality of
      Life Scale - Core 30 questionnaire (QLQ-C30)), and bone pain (assessed on a 5
      point scale from 0=none to 4=intolerable). Ibandronate was generally well
      tolerated. Compared with baseline measurements, the bone pain score was increased
      at the last assessment in both the placebo and 2 mg ibandronate groups, but was
      significantly reduced in the patients receiving 6 mg ibandronate (-0.28+/-1.11, P
      < 0.001). A significant improvement in quality of life was demonstrated for
      patients treated with ibandronate (P < 0.05) for all global health status.
      Overall, at the last assessment, the 6 mg ibandronate group showed significantly
      better functioning compared with placebo (P = 0.004), and had significantly
      better scores on the domains of physical, emotional, and social functioning, and
      in global health status (P < 0.05). Significant improvements in the symptoms of
      fatigue and pain were also observed in the 6 mg ibandronate group. I.v.
      ibandronate treatment leads to significant improvements in quality of life, and
      is an effective and well-tolerated palliative treatment in patients with bone
      metastases due to breast cancer.

PMID- 15251161
TI  - Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity
      in cancer patients treated with cisplatin-based chemotherapy: a randomised,
      double-blind, placebo-controlled study.
AB  - Cisplatin-induced toxicities are mainly caused by the formation of free radicals,
      leading to oxidative organ damage. Plasma concentrations of antioxidants decrease
      significantly during cisplatin chemotherapy for cancer. Forty-eight cancer
      patients treated with cisplatin-based chemotherapy were randomised in a double
      blind manner to receive either supplementation with vitamin C, vitamin E and
      selenium dissolved in a beverage or to receive a placebo beverage. Primary
      outcome measures were the amount of nephrotoxicity and ototoxicity induced by
      cisplatin. No significant differences were found between the two study groups
      with respect to these primary outcome measures. However, patients who achieved
      the highest plasma concentrations of the three antioxidant micronutrients had
      significantly less loss of high-tone hearing. In addition, significant
      correlations were found between the reduced/oxidised vitamin C ratio and
      malondialdehyde (MDA), markers of oxidative stress, and cisplatin-induced
      ototoxicity and nephrotoxicity. The lack of protection against cisplatin-induced
      toxicities in patients in the intervention arm may be related to poor compliance
      and/or inadequate supplementation. Supplementation with a higher dose (intensity)
      and in combination with other antioxidants should be investigated further.

PMID- 15251162
TI  - Quality assurance of the EORTC 26981/22981; NCIC CE3 intergroup trial on
      radiotherapy with or without temozolomide for newly-diagnosed glioblastoma
      multiforme: the individual case review.
AB  - The phase III randomised European Organisation for Research and Treatment of
      Cancer (EORTC) and National Cancer Institute of Canada Clinical Trail Group
      (NCIC) Intergroup trial (EORTC 26981/22981; CE3) compares irradiation alone with
      irradiation plus temozolomide for patients with glioblastoma multiforme (GBM). We
      evaluated the compliance to radiotherapy (RT) guidelines. All 85 recruiting
      centres were invited to participate in the individual case review. Fifty-four
      centres (64%) entering 71% of the patients provided data on one randomly selected
      patient. All participating centres used individual head immobilisation and
      computerised tomography (CT)-based treatment planning. Most (74%) performed three
      dimensional conformal radiotherapy (3-D-CRT) including dose-volume histograms.
      Ninety-four percent performed portal imaging at least once. Planning target
      volume (PTV) and structures at risk were delineated in most of the centres (94%).
      Although the PTV received < 95% of the prescription dose (60 Gy in 2
      Gy/fraction/day) in 39% of the centres; all except 2 centres delivered 50-60 Gy
      to the PTV. The maximum dose to the critical structures exceeded the protocol
      dose constraints in 39% of the reviewed patients, but in only 9% was this over
      the acceptable tolerance dose reported in the literature. We found a high rate of
      compliance with the protocol and general RT guidelines in the centres
      participating in this individual case review. In multicentre trials with a large
      of number of investigators from international and national groups, it is
      essential to confirm the interinstitutional consistency, qualitatively and
      quantitatively.

PMID- 15251163
TI  - Predictors of non-sentinel lymph node metastasis in breast cancer patients.
AB  - In many patients, the sentinel lymph node (SLN) is the sole site of regional
      nodal metastasis. This subgroup of patients would not be expected to benefit from
      completion axillary lymph node dissection (CALND). This study evaluated the
      factors that may determine the likelihood of additional positive nodes in the
      axilla in the presence of sentinel node metastasis. A total of 618 breast cancer
      patients underwent SLN biopsy based on lymphoscintigraphy, intraoperative gamma
      probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V
      injected peritumourally. This was followed by standard axillary node clearance at
      the same operation. Of the 201 patients with a positive SLN, 105 (52%) patients
      had no further positive nodes in the axilla, 96 (48%) patients had additional
      metastasis in non-sentinel lymph nodes (NSLN) upon CALND. In patients with a
      positive SLN, increasing tumour size and tumour grade significantly increased the
      frequency of additional positive nodes on univariate analysis. The number of SLNs
      removed and the number of negative SLNs were significant negative predictors.
      Increasing tumour burden in the sentinel nodes (determined by the number of
      positive SLNs) was significantly associated with increasing likelihood of
      positive NSLNs. Multivariate analysis revealed that the rest of the axilla is
      more likely to be positive if there are more positive than negative SLNs removed
      and more likely to be negative otherwise. A group of cases from one centre
      (Cardiff) were subjected to further detailed analysis. Tumour burden in the
      positive SLN was assessed by measuring the size of metastasis, percentage
      replacement of the SLN by tumour and by documenting extracapsular extension (ECE)
      around the SLN. Of the 64 patients with a positive SLN, 34 (53%) patients had no
      further positive nodes in the axilla, 30 patients (47%) had additional metastasis
      in NSLNs upon CALND. Increasing tumour burden in the SLN was associated with
      additional positive nodes in the axilla. Multivariate analysis revealed that size
      of the SLN metastasis is the most important predictor of involvement of only the
      SLN. Overall, in patients with a positive SLN, the difference in the number of
      positive and negative SLNs removed and size of the metastasis in the SLN, all
      predicted the frequency of additional positive nodes.

PMID- 15251164
TI  - A survey of surgical management of the axilla in UK breast cancer patients.
AB  - The aim of our study was to survey management of the axilla by specialist breast
      surgeons in the United Kingdom (UK). The questionnaire was returned by 371
      surgeons, 366 (99%) were consultants and 96% treated more than 50 cases of breast
      cancer every year. 28% treated patients with invasive breast cancer by axillary
      clearance (AxCl) alone, 5% used sampling alone (AxNS), 40% used both AxCl and
      AxNS, 10% AxCl and sentinel lymph node (SLN) biopsy and 17% AxCl, AxNS and SLN
      biopsy. 9% cleared to level I, and sometimes to level II, 42% to level II and 49%
      to level III. 56% tried to preserve one or multiple intercostal nerves and 44%
      routinely divided the intercostalbrachial nerves. 52% performed SNB within trials
      alone and 36% out side of trials only. A range of techniques were described for
      the SLN biopsy procedure. There is no consistent practice of managing the axilla
      in the UK and standardisation is required. SLN biopsy is performed both within
      and outside of trials and a variety of techniques are used.

PMID- 15251165
TI  - Frequent adverse events after treatment for childhood-onset differentiated
      thyroid carcinoma: a single institute experience.
AB  - Since the mortality rate for childhood differentiated thyroid carcinoma is nearly
      zero, the focus must be to minimise morbidity following treatment. Our aim was to
      analyse early and late adverse events. Twenty-five of 26 children treated between
      1962 and 2002 were evaluated. Median follow-up was 14.2 years (range 0.9-39.4
      years). All underwent total thyroidectomy, 15 (60%) with lymph node dissection
      and 15 (60%) with adjuvant radio-iodide therapy. Mortality was zero. Seven
      developed recurrent disease, two developed a third recurrence. Twenty-one (84%)
      had > or =1 adverse event. Eight had permanent hypoparathyroidism (PH), six
      permanent recurrent nerve paralysis (PRNP) and two Horner's syndrome. Risk
      factors for PH and PRNP were total thyroidectomy with lymph node dissection (RR:
      6.45, P = 0.015) and recurrent nerve tumour encasement (RR: 8.00, P = 0.001),
      respectively. Other adverse events were fatigue (n = 5), scar problems (n = 4)
      and chronic myeloid leukaemia (n = 1). These results emphasise the need to
      improve treatment strategies.

PMID- 15251166
TI  - Helicobacter pylori-CagA seropositivity and nitrite and ascorbic acid food intake
      as predictors for gastric cancer.
AB  - A hospital-based case-control study was carried out between 1994 and 1996 to
      evaluate the risk of gastric cancer (GC) according to Helicobacter pylori-CagA
      (+) seropositivity, nitrite and ascorbic acid intake. Three geographical areas of
      Mexico were selected on the basis of their contrasting dietary patterns and H.
      pylori seroprevalence. Nitrite and ascorbic acid consumption were estimated by
      interview among 211 cases and 454 matched controls. Serum antibodies against IgG
      H. pylori and CagA were detected by immunosorbent assays. The adjusted risk for
      GC was significantly higher among CagA+ subjects compared with those that were
      CagA negative (Odds Ratio (OR)=2.04 95% Confidence Interval (CI) 1.37-3.02 P for
      trend P < 0.001), this effect remained significant among diffuse GC cases (OR
      2.05 95% CI 1.25-3-36). No significant effects due to nitrite and ascorbic
      consumption or interactions of these nutrients with CagA seropositivity were
      detected. Seropositivity to H. pylori CagA+ strains may be an independent factor
      for diffuse GC in Mexico.

PMID- 15251167
TI  - Lethal synergistic effect of cigarette smoke and saliva in an in vitro model:
      does saliva have a role in the development of oral cancer?
AB  - Exposure of oral mucosal cells to cigarette smoke induces oral cancer, presumably
      via the injurious effect of free radicals. To explore the effects of cigarette
      smoke on cells in the presence of saliva, we used peripheral blood lymphocytes
      (PBL) and exposed them to cigarette smoke, alone or in the presence of saliva.
      After 80 min exposure to cigarette smoke alone, a time-dependent cellular loss
      and survival rate of 52% was observed. By contrast, following the exposure of the
      lymphocytes to cigarette smoke in the presence of saliva, less than 20% of the
      cells survived. Saliva secreted from the submandibular/sublingual (Sm/Sl) glands
      was highly cytotoxic, while saliva secreted from the parotid glands was only
      moderately cytotoxic. Redox active iron ions in saliva and aldehydes in cigarette
      smoke were shown to play the major injurious roles in this synergistic
      phenomenon. The salivary-borne redox active iron ions participate in Fenton and
      Haber-Weiss reactions to transform low-reactive free radicals, which originate
      from cigarette smoke into highly-reactive .OH(-)-free radicals. In light of these
      results, a comprehensive mechanism for the induction of oral cancer by cigarette
      smoke is suggested where saliva may be a pivotal player.

PMID- 15251168
TI  - The effects of lycopene on the proliferation of human breast cells and BRCA1 and
      BRCA2 gene expression.
AB  - The purpose of this study was to demonstrate the effects of lycopene, the major
      tomato carotenoid, on the expression of the BRCA1 and BRCA2 genes in three breast
      tumour cell lines, MCF-7, HBL-100, MDA-MB-231 and the fibrocystic breast cell
      line MCF-10a. Flow cytometry analysis showed a G(1)/S phase cell cycle-arrest
      after treatment of the cells with 10 microM lycopene for 48 h. mRNA expression
      was studied by quantitative reverse transcription-polymerase chain reaction using
      the Taqman method. We observed an increase of BRCA1 and BRCA2 mRNA in the
      oestrogen receptor (ER)-positive cell lines (MCF-7 and HBL-100), and a decrease
      (MDA-MB-231) or no change (MCF-10a) in the ER-negative cell lines. BRCA1 and
      BRCA2 proteins were quantified by perfusion affinity chromatography. No variation
      in their expression was observed. These preliminary results on the effects of
      lycopene on the expression of BRCA1 and BRCA2 oncosuppressor genes in breast
      cancer may reflect cross-talk between the oestrogen and retinoic acid receptor
      (RAR) pathways.

PMID- 15251169
TI  - Identification of epidermal growth factor receptor-derived peptides recognised by
      both cellular and humoral immune responses in HLA-A24+ non-small cell lung cancer
      patients.
AB  - The epidermal growth factor receptor (EGFR) is one of the most appropriate target
      molecules for cancer therapy because of its high expression in epithelial
      cancers. A novel EGFR-tyrosine-kinase inhibitor, ZD1839, has been approved as a
      drug for non-small cell lung cancer (NSCLC), and many other agents are now being
      tested in clinical trials. Cytotoxic T lymphocyte (CTL)-directed epitope peptides
      could be another class of useful compounds in EGFR-targeted therapies. However,
      at present, there are no data on CTL-directed peptides of EGFR. Therefore, this
      study aimed to identify immunogenic EGFR-derived peptides in HLA-A24(+) NSCLC
      patients. We report in this study three such EGFR-derived peptides at positions
      54-62, 124-132 and 800-809. These peptides were recognised by both cellular and
      humoral immune responses in most of the peripheral blood mononuclear cells
      (PBMCs) and sera from NSCLC patients that we tested. These results may provide a
      scientific basis for the development of EGFR-based immunotherapy.

PMID- 15251170
TI  - Midkine promoter-driven suicide gene expression and -mediated adenovirus
      replication produced cytotoxic effects to immortalised and tumour cells.
AB  - We examined possible application of a regulatory region of midkine (MK) gene,
      which is frequently upregulated in a number of human tumours but not in normal
      cells, to cancer gene therapy. We examined transcriptional activity of the MK
      genomic fragments in paired cell lines, immortalized cells and their parental
      normal fibroblasts, and found that the MK fragments activated a fused reporter or
      a suicide gene preferentially in the immortalized cells. Recombinant adenoviruses
      (Ad), in which the MK fragment was inserted upstream to the E1A gene (AdMK),
      replicated preferentially in the immortalized cells and were cytotoxie to them.
      Human hepatocellular carcinoma cells were significantly susceptible to AdMK
      compared with human normal fibroblasts in vitro and the replication of AdMK was
      less than that of wild-type Ad in the infected fibroblasts. Hepatocellular
      carcinoma cells infected with AdMK did not form tumours in immunocompromised mice
      and intratumoural injection of AdMK into the hepatocellular carcinoma developed
      in mice retarded the subsequent tumour growth. Expression of E1A and necrosis of
      tumours were detected in AdMK-injected but not control Ad-injected cases. The MK
      promoter-driven suicide gene therapy and -mediated replicative Ad can thereby
      produce cytotoxic effects to immortalized and tumour cells with minimal damage to
      normal cells.

PMID- 15251171
TI  - Cervical cancer in a female-to-male trans-sexual.

PMID- 15251172
TI  - Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3
      gallate: implications for anticancer properties.
AB  - It is believed that anticancer and apoptosis inducing properties of green tea are
      mediated by it's polyphenolic constituents particularly catechins. A number of
      reports have shown that green tea polyphenol (-)-epigallocatechin-3-gallate
      (EGCG) is among the most effective chemopreventive and apoptosis-inducing agents
      present in the beverage. Plant polyphenols are naturally occurring antioxidants
      but they also exhibit prooxidant properties. Over the last several years we have
      shown that various classes of plant polyphenols including flavonoids,
      curcuminoids and tannins are capable of catalyzing oxidative DNA cleavage
      particularly in the presence of transition metal ions such as copper and iron.
      With a view to understand the chemical basis of various pharmacological
      properties of green tea, in this paper we have compared the prooxidant properties
      of green tea polyphenols--EGCG and EC ((-)-epicatechin). The rate of oxidative
      DNA degradation as well as hydroxyl radical and superoxide anion formation was
      found to be greater in the case of EGCG as compared with EC. It was also shown
      that copper mediated oxidation of EC and EGCG possibly leads to the formation of
      polymerized polyphenols. Further, it was indicated that copper oxidized catechins
      were more efficient prooxidants as compared with their unoxidized forms. These
      results correlate with the observation by others that EGCG is the most effective
      apoptosis inducing polyphenol present in green tea. They are also in support of
      our hypothesis that prooxidant action of plant polyphenols may be an important
      mechanism of their anticancer properties. A model for binding of Cu(II) to EC has
      been presented where the formation of quinone and a quinone methide has been
      proposed.

PMID- 15251173
TI  - Property of thimerosal-induced decrease in cellular content of glutathione in rat
      thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate.
AB  - There is a concern on the part of public health community that adverse health
      consequences by thimerosal, a preservative in vaccines for infants, may occur
      among infants during immunization schedule. Therefore, the effect of thimerosal
      on cellular content of glutathione was examined on thymocytes obtained from 4
      week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate.
      Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular
      content of glutathione in a concentration-dependent manner, and the complete
      depletion of cellular glutathione was observed when the cells were treated with
      30 microM thimerosal. L-Cysteine significantly attenuated the actions of
      thimerosal to reduce the glutathione content and to increase the intracellular
      Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal
      induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented
      when the cells suffered oxidative stress induced by H2O2. It may be unlikely that
      thimerosal exerts potent cytotoxic action under the in vivo condition because the
      blood concentration of thimerosal after receiving vaccines does not seem to reach
      micromolar range and nonprotein thiols at micromolar concentrations are present
      in the blood.

PMID- 15251174
TI  - Effects of cooking oil fumes on the genotoxicity and oxidative stress in human
      lung carcinoma (A-549) cells.
AB  - This study investigates the genotoxicity and cytotoxicity of oil fumes, formed
      when peanut oil is heated, on human lung carcinoma pulmonary type II-like
      epithelium cells. The major mutagenic compound (trans-trans-2,4-decadienal, t-t
      2,4-DDE) contained in oil fumes and its effect on the induction of reactive
      oxygen species (ROS) is also discussed. The results indicate that the methanolic
      extract of oil fumes can apparently lead to cytotoxicity and oxidative DNA
      damage. Glutathione (GSH) content, and the activities of antioxidative enzymes
      such as GSH reductase, GSH peroxidase and GSH S-transferase were adversely
      reduced by the methanolic extract of oil fumes. t-t-2,4-DDE could produce
      superoxide anion, hydrogen peroxide and hydroxyl radicals in a phosphate buffer
      (pH 7.4), and form intracellular ROS, determined by dichlorofluorescein assay in
      A-549 cells. Moreover, t-t-2,4-DDE caused significant (P <0.05) oxidative damage
      of the 8-hydroxy-2'-deoxyguanosine formation in A-549 cells at concentrations
      from 50 to 200 microM. These results demonstrated that the DNA damage in A-549
      cells, induced by t-t-2,4-DDE, was related to the ROS formation. The occurrence
      of t-t-2,4-DDE, therefore, was of significance in the genotoxicity of oxidized
      oil and fumes.

PMID- 15251175
TI  - 6-Aminoquinolones: photostability, cellular distribution and phototoxicity.
AB  - Three selected aminoquinolones endowed with a potent antibacterial (compounds 1
      and 2) and antiviral activity (compound 3) have been evaluated for their
      phototoxic properties in vitro. Photostability studies of these compounds
      indicate that compound 3 is photostable whereas compound 1 and in particular,
      compound 2 are rapidly photodegraded upon UVA irradiation, yielding a toxic
      photoproduct. Intracellular localization of these compounds has been evaluated by
      means of fluorescence microscopy using tetramethylrhodamine methyl ester and
      acridine orange, which are specific fluorescent probes for mitochondria and
      lysosomes, respectively. No co-staining was observed with lysosomal stain for all
      the test compounds. On the contrary compound 3 was found to be specifically
      incorporated in mitochondria. The compounds exhibited remarkable phototoxicity in
      two cell culture lines: human promyelocytic leukaemia (HL-60) and human
      fibrosarcoma (HT-1080). The quinolone-induced photodamage was also evaluated
      measuring the photosensitizing cross-linking in erythrocyte ghost membranes, the
      strand breaks activity and oxidative damage on plasmid DNA. The results show that
      these derivatives are able to photoinduce crosslink of erythrocytes spectrin,
      whereas do not significantly photocleavage DNA directly, but single strand breaks
      were observed after treatment of photosensitized DNA with two base excision
      repair enzymes, Fpg and Endo III respectively.

PMID- 15251176
TI  - An inhibitor of p38 MAP kinase downregulates cytokine release induced by sulfur
      mustard exposure in human epidermal keratinocytes.
AB  - Sulfur mustard (2,2'-dichlorodiethyl sulfide, SM) is a potent alkylating agent
      that induces skin vessication after cutaneous exposure. Previous work has
      revealed that SM induces the production of inflammatory cytokines, including IL
      8, IL-6, TNF-alpha, and IL-1beta, in keratinocytes. The p38 MAP kinase (MAPK14)
      signaling pathway is activated via phosphorylation in response to cellular stress
      and has been implicated in the upregulation of cytokines in response to stress.
      We investigated the role of p38 MAP kinase in inflammatory cytokine upregulation
      following SM exposure. A dose response study in cultured human epidermal
      keratinocytes (HEK) revealed increasing phosphorylation of p38 MAP kinase in
      response to increasing concentrations of SM. A time course at the 200 microM
      exposure revealed that p38 MAP kinase phosphorylation is induced by 15 min post
      exposure, peaks at 30 min and is sustained at peak levels until 8 h post
      exposure. Phosphorylation of the upstream kinase MKK3/6 was also detected. Assay
      of the SM-exposed HEK culture media for cytokines revealed that exposure to 200
      microM SM increased IL-8, IL-6, TNF-alpha, and IL-1beta. When cells exposed to
      200 microM SM were treated with the p38 MAP kinase inhibitor SB203580, the levels
      of IL-8, IL-6, and TNF-alpha and IL-1beta were significantly decreased when
      compared with cells that were untreated. These results show that p38 MAP kinase
      plays a role in SM-induced cytokine production in HEK and suggest that inhibiting
      this pathway may alleviate the profound inflammatory response elicited by
      cutaneous SM exposure.

PMID- 15251177
TI  - Effects of ethanol on mouse embryonic brain development and heat shock protein 73
      expression.
AB  - Effects of ethanol on brain development and heat shock protein 70 (HSP70)
      expression were investigated in mouse embryos using the whole embryo culture, mid
      brain culture, and streptavidin-biotin peroxidase complex (SABC) method. In the
      whole embryo culture, ethanol (1, 2 and 4 mg/ml) inhibited brain development dose
      dependently and the most prevalent abnormality was the open cephalic neural tube.
      At doses of 1 and 2 mg/ml, ethanol significantly decreased constitutive HSP70
      (HSP73) expression level compared to control values in embryonic brain areas. In
      mid-brain culture, ethanol exposure (from 1 to 16 mg/ml) during early neuroblast
      differentiation inhibited neuronal differentiation and proliferation. These
      results suggest that ethanol may affect embryonic brain development by decreasing
      HSP73 expression level as well as inhibiting neuronal differentiation and
      proliferation during the organogenic period.

PMID- 15251178
TI  - In vitro antigenotoxic potential of acitretin in human lymphocytes treated with
      the antineoplastic alkylating agent ASE (NSC-71964).
AB  - Acitretin is widely used in the systemic treatment of severe forms of psoriasis
      and other skin disorders. ASE, namely 3beta-hydroxy-13alpha-amino-13,17-seco
      5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloro-ethyl)amino phenylacetate
      (AzaSteroidalEster, NSC-71964), is an alkylating agent with antineoplastic
      activity and mutagenic properties. The aim of this study was to investigate the
      possible genotoxic and/or antigenotoxic effects of acitretin in human lymphocyte
      cultures in vitro, using sister chromatid exchange (SCE) and cytokinesis-blocked
      micronucleus (CBMN) assays. Micronucleus (MN) analysis was achieved in
      combination with fluorescence in situ hybridization (FISH), using an alpha
      satellite DNA pancentromeric probe. It was found that acitretin alone
      demonstrated no clastogenic or aneugenic activity. However, simultaneous
      incubation of lymphocyte cultures with ASE and acitretin resulted in a reduction
      of ASE-induced SCEs. For MN analysis lymphocytes were treated with ASE and
      acitretin at 21 and 41 h after culture initiation, corresponding to G1 and G2
      phases, respectively, and lasted until cell harvest. Acitretin caused a decrease
      in ASE-induced MN when treatment of cells started at 41 h, but exerted no effect
      on them when treatment started at 21 h. These findings suggest that acitretin
      exerts antigenotoxic effects in human lymphocyte cultures, the expression of
      which may be related to the cycle phase of the cells upon onset and duration of
      the treatment, at least as far as MN frequency is concerned.

PMID- 15251179
TI  - Possible modulating actions of plant extracts on the chromosome breaking activity
      of MMC and Ara-C in human lymphocytes in vitro.
AB  - Plants popularly used as medicine have been seen as promising natural agents by
      the pharmaceutical industry. In the present study the action of Psidium guajava
      L. (Pg) and Achillea millefolium L. (Am) infusions on chromosomal aberration
      formation in human lymphocyte system in vitro was assessed, associating them with
      the alkylating agent mitomycin C (MMC) and the DNA repair inhibitor cytosine-beta
      arabin-furanoside (Ara-C). The cells were cultivated for 72 h and treated
      continuously with Pg and the Am infusions at dosages of 2.62 x 10(-4) g and 3.5 x
      10(-4) g/ml culture medium, respectively. Treatments with MMC (0.30 microg/ml) or
      Ara-C (5 x 10(-7) microg/ml) were administered after 48 h of cell culture. Each
      samples (five individual) were exposed to nine treatments (control with PBS; Pg;
      Am; MMC; MMC+Pg; MMC+Am; Ara-C; Ara-C+Pg; and Ara-C+Am) and 100 cells were
      analyzed per cell culture. The used doses of each infusion did not cause
      clastogenic effects significantly different to the negative control (control=1%;
      Pg=2.2%; Am=1.8%). Nevertheless, the aberrant cell frequency after MMC treatment
      was significantly increased by the Am infusion (MMC=32.4%; MMC+Pg=36.2%;
      MMC+Am=44%), especially when the chromatid break types number was scored
      (MMC=151; MMC+Pg=173; MMC+Am=249). Regarding DNA repair inhibition by Ara-C, the
      Pg infusion caused a significant reduction in aberrant cell frequency (Ara
      C=15.8%; Ara-C+Pg=11%; Ara-C+Am=14.4%), only when the chromatid break types
      number was scored (Ara-C=63; Ara-C+Pg=40; Ara-C+Am=58). These results indicate
      that the plant infusions per se do not have clastogenic activity, but can
      influence the clastogenic action of MMC and Ara-C on DNA break induction, in
      vitro.

PMID- 15251180
TI  - Evaluation of the teratogenicity of fennel essential oil (FEO) on the rat embryo
      limb buds culture.
AB  - The use of FEO as a remedy for control of primary dysmenorrhea increases concern
      about its potential teratogenicity due to its estrogen-like activity. Limb bud
      mesenchymal cells, when grown in high-density cultures, can be differentiated
      into a number of cell types including cartilage and muscle. These cells have been
      used extensively for in vitro studies of chondrogenesis. Therefore, we used limb
      bud cells and Alcian blue staining method that is specific for staining cartilage
      proteoglycan, to determine the teratogenic effect of FEO. Limb bud cells obtained
      from day 13 rat embryo were cultivated and exposed to various concentrations of
      FEO for 5 days at 37 degrees C and the number of differentiated foci were
      counted. Retinoic acid (90 microg/ml) was chosen as positive standard control.
      The differentiation was also evaluated using limb bud micromass culture using
      immunocytochemical techniques and BMP-4 antibody. The results showed that FEO at
      concentration as low as 0.93 mg/ml produced a significant reduction in the number
      of stained differentiated foci. However, this reduction was due to cell loss,
      determined by neutral red cell viability assay, rather than to be related to
      decrease in cell differentiation. These findings suggest that the FEO at the
      studied concentrations may have toxic effect on fetal cells, but there was no
      evidence of teratogenicity.

PMID- 15251181
TI  - Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity.
AB  - Paper presents the effects of the newly synthesized fullerol C60(OH)22 on the
      growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)
      induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition
      was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance
      (ESR) "trapping" method was used to investigate OH-radical scavenger activity of
      fullerol during Fenton's reaction. At a range of nanomolar concentrations
      fullerol induced cell growth inhibition, which was cell line, dose and time
      dependent. Fullerol also strongly suppressed DOX-induced cytotoxicity at all
      concentrations regardless the time of fullerol addition. Proanthocyanidins added
      as single agent to MCF-7 cell culture for 48 h induced low growth inhibition but
      in combination with DOX strongly decreased DOX cytotoxicity. Fullerol was found
      to be a potent hydroxyl radical scavenger: the relative intensity of ESR signals
      of DMPO-hydroxyl radical (DMPO-OH) spin adduct decreased by 88% in the presence
      of 0.5 microg/ml of fullerol. The obtained results suggest that antiproliferative
      effect of the fullerol and its protective effect on DOX-induced cytotoxicity
      might be mediated through hydroxyl-radical scavenger activity of C60(OH)22.

PMID- 15251182
TI  - Experimental survey of non-clonogenic viability assays for adherent cells in
      vitro.
AB  - Results of rapid cell viability assays were experimentally compared in order to
      reveal the most suitable test for in vitro investigations of the combination of
      photodynamic therapy (PDT) with chemotherapeutic drugs. meso-Tetra(3
      hydroxyphenyl)-chlorin (m-THPC) accumulating in cell membranes and meso-tetra(4
      sulfonatophenyl)-porphin (TPPS4) accumulating in lysosomes were used as
      photosensitisers. Doxorubicin that localises, mainly, to nucleus and vincristine
      that binds to microtubules were used as cytostatic drugs. Two adherent rodent
      cell lines, baby hamster kidney (BHK-21) and murine hepatoma (MH-22A), were used
      to examine the contribution of a cell. We tested cytotoxicity assays of the main
      groups of fast (non-clonogenic) methods of cell viability measuring. Plasma
      membrane integrity was estimated by trypan blue exclusion and LDH leakage,
      metabolic activity was tested by [3H]-thymidine incorporation and MTT assay, loss
      of monolayer adherence was measured by staining with crystal violet and CyQUANT.
      The most sensitive test in each case was the assay related to the site of the
      direct damage, and measurement of the loss of monolayer adherence proved to be as
      sensitive assay as the damage-specific one. All the assays applied, except for
      the LDH release, revealed a higher effect of combination of m-THPC-mediated
      phototreatment and doxorubicin compared to either of the single treatments.

PMID- 15251183
TI  - Evaluation of different toxicity assays applied to proliferating cells and to
      stratified epithelium in relation to permeability enhancement with glycocholate.
AB  - The purpose of the present study was to evaluate different toxicity assays for
      use on proliferating buccal TR146 cells and on stratified TR146 epithelium and to
      compare these results to the permeability enhancing effect of glycocholate (GC).
      Both the proliferating cells and the epithelium were exposed to different GC
      concentrations for 4 h. The MTS/PMS assay and neutral red (NR) retention were
      performed along with quantitation of ATP, lactate dehydrogenase (LDH) and
      extracellular protein. The toxicity was calculated as the IC50 value relative to
      the control. Increase in 3H-mannitol permeability across the epithelium
      concurrent with a decrease in the transepithelial electrical resistance (TEER)
      was also determined. The robustness of the epithelium was significantly higher
      than that of the proliferating cells (P <0.01). The ATP assay was the most
      sensitive assay with IC50 values of 6.4 and 11.5 mM for proliferating cells and
      epithelium, respectively. Intracellular LDH quantitation was the least sensitive
      method and extracellular LDH could not be used as a measure of toxicity partly
      due to interaction between LDH and GC. The effect on permeability and TEER could
      be correlated to the IC50 values obtained for the epithelium. The present study
      clearly demonstrates that for a correlation between toxicity and permeability
      enhancement, both studies should be performed on the epithelium.

PMID- 15251184
TI  - Microarray analysis of gene regulation in the Hepa1c1c7 cell line following
      exposure to the DNA methylation inhibitor 5-aza-2'-deoxycytidine and 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Differential expression of various genes was observed in the Hepa1c1c7 cell line
      following exposure to the DNA methylation inhibitor 5-aza-2'-deoxycytidine (AzaC)
      and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AzaC treatment generally
      affected genes induced by TCDD by modulating their induction levels. Induction of
      several genes, such as receptor (calcitonin) activity modifying protein 3 (Ramp3)
      by TCDD was enhanced by AzaC, although AzaC by itself was without effect. Some
      genes, such as frequently rearranged in advanced T-cell lymphomas (Frat1), were
      up-regulated by AzaC alone, with this induction being negatively affected by
      TCDD. Other genes were induced by AzaC, TCDD and their co-treatment. In contrast,
      many genes such as small proline-rich protein 1A (Sprr1a) and 2A (Sprr1a) were up
      regulated by AzaC, but not significantly affected by TCDD. In addition, a group
      of genes was down-regulated by AzaC, TCDD and their co-treatment. These findings
      suggest the TCDD-dependent regulation of various genes to be influenced by
      cellular DNA methylation status.

PMID- 15251185
TI  - Percutaneous absorption of 5 glycol ethers through human skin in vitro.
AB  - Absorption across full thickness human skin was evaluated in vitro for five
      selected glycol ethers. Skin membranes were settled on static diffusion cells and
      both neat and 50% water diluted glycol ethers were applied on the donor chamber
      for 8 h. The amount of glycol ethers permeated into the receptor fluid was
      measured by gas chromatograph equipped with flame ionization detector (GC-FID).
      For neat solvents, permeation coefficient Kp ranged from 0.06 to 0.83 cm h(-1)
      10(-3) respectively for DEGBEA and EGMEA while for 50% v/v diluted glycol ethers
      it varied from 0.08 to 1.81 cm h(-1) 10(-3) respectively for DPGME and EGMEA.
      These experiments show a statistically significant (Student's t-test, P <0.05)
      increase in permeation coefficients from neat to 50% water diluted glycol ethers
      and the same trend can be observed in fluxes and lag times. Only DPGME show an
      opposite behaviour. These results confirm the good ability of these solvents of
      permeating the skin and show that they could represent a risk for their potential
      dermal absorption both for workers and for occasional exposures, since the
      average lag time is 1.57 h.

PMID- 15251186
TI  - In vitro alveolar cytotoxicity of soluble components of airborne particulate
      matter: effects of serum on toxicity of transition metals.
AB  - Respiration of fossil fuel-derived airborne particulate matter (PM) has been
      linked to various pulmonary disorders. Transition metals contained in such PM,
      such as zinc, iron and vanadium, have been suggested as the primary culprits in
      PM-induced pulmonary distress by rat instillation studies. In this study, the
      cytotoxicity of zinc, iron, and vanadium on confluent monolayers of rat alveolar
      epithelial cells was evaluated as the inhibition of cellular succinate
      dehydrogenase metabolic activity as quantified via the MTT assay. In addition,
      the effect of culture medium serum concentration on the toxicities of these three
      metals was investigated. Of the three metals tested, zinc was the most toxic,
      with an EC50 of 0.6 mM in culture medium with 10% serum; vanadium and iron had
      EC50's of 3 and 4 mM, respectively. Serum in culture medium was found to
      substantially reduce the apparent toxicity of zinc: EC50's for zinc ranged from
      0.6 mM in 10% serum to 0.1 mM in serum-free medium. Zinc toxicity analyses in
      various culture medium conditions demonstrated that the toxicity-reducing effect
      of serum was due largely and perhaps entirely, to serum albumin. Some, but not
      all of the effect of serum and albumin on zinc toxicity is apparently due to zinc
      albumin binding.

PMID- 15251187
TI  - Assessment of contact allergens by dissociation of irritant and sensitizing
      properties.
AB  - The human organotypic skin explant culture (hOSEC) model is a promising
      alternative in vitro model for screening contact allergens. In this model, the
      chemical-induced migration of Langerhans cells (LCs) out of the epidermis,
      evaluated after a 24-h exposure period, is used as a measure of sensitizer
      potential. As skin irritants can also induce LC migration it is essential that
      concentrations of test chemicals are used that are not even weakly irritant.
      Using the hOSEC irritation model chemicals are classified as weak irritants if
      they are toxic after a 48-h exposure period. Toxicity is determined by methyl
      green-pyronine (MGP) staining of hOSEC. We studied three frequently used non
      sensitizing skin irritants and six potent or frequent human sensitizers in a dose
      response. A complete discrimination between non-sensitizers and contact
      sensitizers was obtained for the chemicals tested when the concentrations used
      were lower than the weak irritant concentrations. Frequency of positive allergen
      reactions in patch test of human populations correlated with the difference
      between weak irritant concentrations and the lowest concentration inducing
      significant LC migration. Sensitizer potency correlated with chemical irritancy
      as determined by keratinocyte death. For the compounds tested, the hOSEC model
      predicted allergenicity in humans better than the guinea pig maximization test
      and the mouse local lymph node assay.

PMID- 15251188
TI  - A short-term in vitro gill culture system to study the effects of toxic (copper)
      and non-toxic (cortisol) stressors on the rainbow trout, Oncorhynchus mykiss
      (Walbaum).
AB  - A short-term (24 h) method of gill filament culture system was developed to
      predict the effects of environmental contamination and stress in fish. Gill
      culture system containing two or three rainbow trout gill filaments in sterile
      glutamine supplemented Leibovitz 15 (L-15) media was submitted for 24 h to six
      different treatments: (i) CONT (control, medium only); (ii) CORT (cortisol, 0.28
      microM cortisol); (iii) BLOCK (glucocorticoid receptor blocker, 14 microM RU
      486); (iv) CORT+BLOCK (cortisol and blocker, 0.28 microM cortisol+14 microM RU
      486); (v) CORT+CU (cortisol and copper, 100 microM CuSO4+0.28 microM cortisol);
      (vi) CU (copper, 100 microM CuSO4). After 24 h, the overall gill structure and
      cellular components resembled those of salmonids in vivo. Lactate dehydrogenase
      (LDH) activity in the culture media increased in the CORT+CU and CU groups but
      was significantly lower in the CORT+CU compared to CU group. Apoptotic cells
      increased in the CORT and CORT+BLOCK. The numbers of glucocorticoid (GR) receptor
      positive cells were lower in the CU group. This short-term culture system seems
      to be suitable for studying the effects of both external and internal stress
      effectors (toxicants and hormones respectively), as it contains all cell types
      found in the gills and the cells give similar biological response as in vivo.

PMID- 15251189
TI  - Comparison of alamar blue and MTT assays for high through-put screening.
AB  - The performance of alamar blue and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide (MTT) cell viability assays in a high through-put format were
      compared. A total of 117 drugs chosen for their wide range of therapeutic areas
      were screened at 10 microM using both assays in human hepatoma cell line HepG2.
      Except for terfenadine and astemizole, which performed consistently in both
      assays, the alamar blue assay was slightly more sensitive than the MTT assay for
      most compounds. The MTT assay was less sensitive detecting an effect for
      daunorubicin and trifluoperazine. Seven drugs, astemizole, daunorubicin,
      ellipticine, fluphenazine, terfenadine, thioridazine and trifluoperazine, had
      percent viability results of 55% or less in the alamar blue assay at the single
      point screen. These were re-tested in both assays for reconfirmation of
      cytotoxicity and determination of the EC50 values. Except for daunorubicin, the
      EC50 values were comparable in both assays. Based on these results and the Z'
      factor assessment of assay quality, both assays provided useful information to
      identify in vitro cytotoxic drugs at early stages of drug candidate selection.
      However, careful interpretation of data is warranted due to the possibility of
      false positive or negative results caused by inducers and/or inhibitors of
      metabolic enzymes that are responsible for transformation of cell toxicity end
      points, as we demonstrated using dicumarol.

PMID- 15251190
TI  - Significant contamination of superoxide dismutases and catalases with
      lipopolysaccharide-like substances.
AB  - Commercially available superoxide dismutase (SOD) and catalase induced remarkable
      morphological changes in cultured peritoneal resident macrophages (PRMs). The
      morphology resembled that of cells stimulated with various macrophage-activating
      substances such as bacterial lipopolysaccharides (LPS). PRMs treated with SOD and
      catalase for 24 h produced a significant amount of nitric oxide. Peritoneal
      thioglycollate-exudated macrophages (PEMs) that were induced to die by combined
      treatment with LPS and cycloheximide (protein synthesis inhibitor) were killed by
      the treatment with SOD and catalase in the presence of cycloheximide. The effect
      of SOD and catalase was heat-resistant and was not found in PEMs of the C3H/HeJ
      mouse, an LPS low responder strain. These results strongly indicated the presence
      of LPS-like substances in the sample of SOD and catalase used. An examination of
      commercially available SOD and catalase samples for the presence of LPS-like
      substances demonstrated that many were contaminated. The LPS contamination was
      directly confirmed by bacterial endotixins test. It is quite important to take
      into consideration that commercially available SODs and catalases may be
      contaminated with LPS and the contaminants may affect the results of studies.

PMID- 15251191
TI  - Replacement of ether with alternate volatile anesthetics for collection of rat
      serum used in embryo culture.
AB  - BACKGROUND: The traditional anesthetic used for collection of the serum culture
      medium for whole rat embryo culture studies has been ether. However ethical
      concerns have been raised due to the irritant nature of the vapour and safety
      concerns due to the risk of fire. METHODS: Growth and development of gestation
      day 9.5 rat embryos cultured for 48 h in serum collected from rats anesthetised
      with either ether, isoflurane or halothane were compared. RESULTS: There were no
      differences in any of the parameters used to assess embryonic development when
      embryos were grown in serum collected using either ether or isoflurane
      anesthetics. However, when embryos grown in serum collected using ether or
      halothane were compared, embryonic development was similar in all respects,
      except for a reduced number of embryos turned to become fully dorsally convex in
      the halothane group (p <0.05). CONCLUSIONS: The data indicate that isoflurane is
      an appropriate alternative to ether for collection of the serum culture medium
      for whole rat embryo culture, while halothane may cause some delay of embryonic
      development.

PMID- 15251192
TI  - The Tinsley LCR Databridge Model 6401 and electrical impedance measurements to
      evaluate skin integrity in vitro.
AB  - Electrical impedance is used to confirm skin integrity for in vitro dermal
      regulatory testing and as a tool to evaluate skin condition to determine the
      irritation and corrosion potential of various chemicals and personal care
      products. In this experiment, samples of dermatomed human skin were mounted onto
      static diffusion cells (0.64 cm2) maintained at 32 degrees C. Following
      equilibration with 0.9% saline in the donor and receptor chambers, an impedance
      measurement was taken with a Tinsley LCR Databridge Model 6401 set in the
      resistance mode (R) and in (a) the serial-equivalent mode (SER) with an
      alternating current (AC) frequency of 100 hertz (Hz), (b) SER and 1000 Hz, (c)
      parallel-equivalent mode (PAR) and 100 Hz, and (d) PAR and 1000 Hz. With the
      databridge set in the SER-equivalent mode and an AC frequency of 1000 Hz, the
      minimum (7.2 kOmega), maximum (10.0 kOmega), and median (8.6 kOmega) impedance
      values exhibited a limited response range (2.8 kOmega). However, when the Tinsley
      6401 was set in the PAR-equivalent mode at the lower AC frequency of 100 Hz the
      minimum (16.7 kOmega), maximum (134.6 kOmega), median (83.2 kOmega), and range
      (117.9 kOmega) of values were the highest obtained. The results confirm that the
      operator-selected settings on the Tinsley LCR Databridge Model 6401 affect the
      impedance measurement and the dynamic range of values observed for dermatomed
      human skin in vitro.

PMID- 15251193
TI  - What drives bacteria to produce a biofilm?
AB  - Nearly 40 years ago, Dr. R.J. Gibbons made the first reports of the clinical
      relevance of what we now know as bacterial biofilms when he published his
      observations of the role of polysaccharide glycocalyx formation on teeth by
      Streptococcus mutans [Sci. Am. 238 (1978) 86]. As the clinical relevance of
      bacterial biofilm formation became increasingly apparent, interest in the
      phenomenon exploded. Studies are rapidly shedding light on the biomolecular
      pathways leading to this sessile mode of growth but many fundamental questions
      remain. The intent of this review is to consider the reasons why bacteria switch
      from a free-floating to a biofilm mode of growth. The currently available wealth
      of data pertaining to the molecular genetics of biofilm formation in commonly
      studied, clinically relevant, single-species biofilms will be discussed in an
      effort to decipher the motivation behind the transition from planktonic to
      sessile growth in the human body. Four potential incentives behind the formation
      of biofilms by bacteria during infection are considered: (1) protection from
      harmful conditions in the host (defense), (2) sequestration to a nutrient-rich
      area (colonization), (3) utilization of cooperative benefits (community), (4)
      biofilms normally grow as biofilms and planktonic cultures are an in vitro
      artifact (biofilms as the default mode of growth).

PMID- 15251194
TI  - Cloning, expression, and characterization of 5-aminolevulinic acid synthase from
      Rhodopseudomonas palustris KUGB306.
AB  - The hemA gene encoding 5-aminolevulinic acid synthase (ALAS) was cloned from the
      genomic DNA of photosynthetic bacterium Rhodopseudomonas palustris KUGB306. The
      deduced protein (ALAS) of this gene contained 409 amino acids. The hemA gene was
      subcloned into an expression vector pGEX-KG and the encoded protein was
      overexpressed as a fusion protein with glutathione-S-transferase (GST) in
      Escherichia coli BL21. The recombinant ALAS was purified and isolated free of the
      fusion partner (GST) by affinity purification on glutathione-Sepharose 4B resin
      and cleavage of the purified fusion protein by thrombin protease. The optimum pH
      and temperature of the recombinant ALAS was found to be at pH 7.5-8.0 and 35-40
      degrees C, respectively. The Km value of the enzyme was 2.01 mM for glycine and
      49.55 microM for succinyl-CoA. The enzyme activity was strongly inhibited by
      Pb2+, Fe2+, Co2+, Cu2+, and Zn2+ at 1 mM, but slightly affected by Mg2+ and K+.
      The recombinant ALAS required pyridoxal 5'-phosphate (PLP) as a cofactor for
      catalysis. Removal of this cofactor led to complete loss of the activity.
      Ultraviolet-visible spectroscopy with the ALAS suggested the presence of an
      aldimine linkage between the enzyme and PLP.

PMID- 15251195
TI  - Characterization of florfenicol resistance among calf pathogenic Escherichia
      coli.
AB  - Three floR genes were cloned from calf pathogenic Escherichia coli strains, and
      the efflux-mediated accumulation of florfenicol in the floR gene-JM109 E. coli
      system was determined by HPLC. The floR genes resulted in a 1356-bp fragment
      covering the ORF in region 66-1280 coding for 404 amino acids. The common motifs
      of 12-transmembrane segments efflux pumps family were conserved in the deduced
      floR amino acid sequences. HPLC results indicated a significant difference in
      florfenicol accumulation between florfenicol-resistant strains and the
      susceptible strains, which was almost reversed by the addition of a proton motive
      force blocker. These results suggest that the florfenicol resistance mediated by
      the floR gene involves active efflux of florfenicol.

PMID- 15251196
TI  - Verticillium fungicola var. fungicola affects Agaricus bisporus cultivation in
      Mexico.
AB  - Verticillium fungicola is responsible for dry bubble disease of the button
      mushroom Agaricus bisporus. Investigations performed in 2001 showed that mushroom
      cultures were affected by V. fungicola var. aleophilum in North American farms
      whereas they were affected by V. fungicola var. fungicola in European farms. The
      latter variety was not found in North America. Studies carried out on
      Verticillium isolates collected in Mexico in 2002 revealed that they belong to
      the variety fungicola. The hypothesis of the introduction of the variety
      fungicola from Europe through the import of material or machines used for
      mushroom cultivation is proposed.

PMID- 15251197
TI  - Mutations in the chloramphenicol acetyltransferase (S61G, Y105C) increase
      accumulated amounts and resistance in Pseudomonas aeruginosa.
AB  - A chloramphenicol acetyltransferase (catB7) gene containing two point mutations,
      181A/G and 314A/G, has been recently reported to be a determinant for high-level
      chloramphenicol resistance phenotype in a Pseudomonas aeruginosa strain PAhcr1.
      The mutant CATB7 was further characterized in vitro and in vivo to elucidate the
      molecular basis of high-level resistance. CAT assay demonstrated that the mutant
      and wild-type recombinant CATB7 had similar specific activities. Dot blotting
      revealed that the accumulated amounts of CATB7 in P. aeruginosa strains PAO1 and
      PAhcr1 were proportionate to the respective anti-chloramphenicol level. Site
      directed mutagenesis showed that G61S and Y105C contributed synergistically to
      the PAhcr1 resistance phenotype. It could be proposed that the mutant CATB7 was
      more structurally stable than catalytically efficient as a chloramphenicol
      resistance determinant in PAhcr1.

PMID- 15251198
TI  - The streptococcolytic enzyme zoocin A is a penicillin-binding protein.
AB  - Zoocin A is a streptococcolytic enzyme produced by Streptococcus equi subsp.
      zooepidemicus 4881 that has an unknown site of action on the peptidoglycans of
      susceptible organisms. Analysis of a mutant strain in which the genes for zoocin
      A and resistance to zoocin A were inactivated revealed that this strain was more
      susceptible to beta-lactam antibiotics than the parental organism. Purified
      zoocin A had weak beta-lactamase activity, bound radioactive penicillin
      covalently, and its streptococcolytic activity was inhibited by penicillin. Thus,
      zoocin A is a penicillin-binding protein and presumably is a D-alanyl
      endopeptidase.

PMID- 15251199
TI  - Mercuric resistance genes in gram-positive oral bacteria.
AB  - Mercury-resistant bacteria isolated from the oral cavities of children carried
      one of two types of merA gene that appear to have evolved from a common ancestor.
      Streptococcus oralis, Streptococcus mitis and a few other species had merA genes
      that were very similar to merA of Bacillus cereus strain RC607. Unlike the B.
      cereus RC607 merA gene, however, the streptococcal merA genes were not carried on
      Tn5084-like transposons. Instead, comparisons with microbial genomic sequences
      suggest the merA gene is located on a novel type II transposon. Coagulase
      negative staphylococci and Streptococcus parasanguis had identical merA genes
      that represent a new merA variant.

PMID- 15251200
TI  - Sigma(s)-dependent regulation of yehZYXW, which encodes a putative osmoprotectant
      ABC transporter of Escherichia coli.
AB  - The Escherichia coli yehZYXW operon encodes a putative osmoprotectant uptake
      system of the ABC transporter family. yehZ is identical to osmF, an osmotically
      inducible gene identified previously. Construction and analysis of a yehZ-lacZ
      transcriptional fusion demonstrated that yehZ is inducible not only by
      osmolarity, but also upon entry into stationary phase. The osmotic and growth
      phase regulations operate at a unique promoter, yehZp, and are totally dependent
      on the stress specific sigma factor sigma(s). The yehZYXW encoded ABC transporter
      appears as an additional element of the global stress response controlled by
      sigma(s).

PMID- 15251201
TI  - Aggregation of mycobacteria caused by disruption of fibronectin-attachment
      protein-encoding gene.
AB  - The fibronectin-attachment protein (FAP) is conserved among several species of
      mycobacteria. Although this protein is associated with attachment and
      internalization of bacteria to host cells via fibronectin, the physiological role
      of the protein still remains unclear. To investigate this point, we generated FAP
      gene disruptant in Mycobacterium smegmatis. The gene disruption, verified by
      Southern blot and PCR analysis, induced changes on the bacteria, which are
      associated with strong aggregation and alteration of cell surface properties.
      Increased hydrophobicity and Congo red accumulation was observed in the FAP gene
      disruptant. In addition, the complementation experiment demonstrated that the
      corresponding gene restored wild type morphology in the disruptant. These results
      indicate that the FAP affects the cell surface properties, and its deletion lead
      to enhanced aggregation of the M. smegmatis.

PMID- 15251202
TI  - A hydrogen-evolving enzyme is present in Frankia sp. R43.
AB  - The ability to evolve hydrogen using methyl viologen as an electron donor was
      assayed in the nitrogen-fixing actinomycetes Frankia sp. R43 and Frankia sp. KB5.
      To further examine the nature of hydrogen-evolving enzymes that may be present in
      these organisms immunological studies were performed. Under anaerobic conditions
      (both nitrogen-limiting and nitrogen-containing) Frankia sp. R43 but not Frankia
      sp. KB5 evolved hydrogen,which was not linked to NAD-reducing activity.
      Immunological analysis of total protein from Frankia sp. R43 and Frankia sp. KB5
      using an antiserum raised against Ralstonia eutropha HoxF, recognized an antigen
      in Frankia sp. R43 but not in Frankia sp. KB5. Immunogold labeling using
      antibodies raised against the R. eutropha HoxH recognized sites in both hyphae
      and vesicles of Frankia sp. R43, but not in Frankia sp. KB5. Based on these
      physiological and immunological findings, we conclude that Frankia sp. R43 has a
      hydrogen-evolving hydrogenase.

PMID- 15251203
TI  - Antimicrobial effects of sanitizers against planktonic and sessile Listeria
      monocytogenes cells according to the growth phase.
AB  - This study was designed to investigate the individual or combined effects of
      sanitizers on survival of planktonic or sessile Listeria monocytogenes cells at
      different phase of growth. The sanitizers tested included: (i) acetic acid (pH
      5.0), (ii) NaOH (pH 12.0), (iii) 10% Na2SO4, (iv) 10% Na2SO4 and acetic acid (pH
      5.0), (v) 10% Na2SO4 and NaOH (pH 12.0), (vi) a quaternary ammonium (20 ppm) and
      (vii) glyceryl monolaurate (75 ppm). Results revealed a great efficacy of
      alkaline treatments on both sessile and planktonic cells with a slightly higher
      resistance of 6 h biofilms. Quaternary ammonium appeared very effective in
      killing more than 98% of cells, but a resistance of 7 days biofilm was observed.
      Other sanitizers did not succeed in inhibiting totally the pathogen but acted in
      a similar way on both sessile and planktonic cells. Renewing the medium or not do
      not seem to be the major cause of a resistance emergence.

PMID- 15251204
TI  - Global distribution of nearly identical phage-encoded DNA sequences.
AB  - Phages, the most abundant biological entities on the planet, play important roles
      in biogeochemical cycling, horizontal gene transfer, and defining microbial
      community composition. However, very little is known about phage diversity or
      biogeography, and there has not yet been a systematic effort to compare the
      phages found in different ecosystems. Here, we report that T7-like Podophage DNA
      polymerase sequences occur in every major biome investigated, including marine,
      freshwater, sediment, terrestrial, extreme, and metazoan-associated. The majority
      of these sequences belong to a unique clade that is only distantly related to
      cultured isolates. Some identical T7-like phage-encoded DNA polymerase genes from
      this clade were >99% conserved at the nucleotide level in multiple different
      environments, suggesting that these phages are moving between biomes in recent
      evolutionary time and that the global genomic pool for T7-like phages may be
      smaller than previously hypothesized.

PMID- 15251205
TI  - Development of PCR assay to identify Pseudomonas fluorescens and its biotype.
AB  - The paper provides a simple protocol that uses the polymerase chain reaction to
      amplify a specific portion of the 16S gene, allowing the recognition of
      Pseudomonas fluorescens from other group I Pseudomonas. The amplified DNA
      patterns of 16S rRNA and ITS1, from the restriction fragment length polymorphisms
      VspI, HaeIII and TaqI digestion, produced band patterns that distinguished the
      biotypes of Ps. fluorescens. In addition to distinguishing the biotypes C and 3
      we used a phenotypical method for levan production.

PMID- 15251206
TI  - Sustained glycolytic oscillations--no need for cyanide.
AB  - Using fluorescence spectroscopy we detected long trains of macroscopic
      oscillations in the glycolytic pathway, in whole cell suspensions of
      Saccharomyces cerevisiae, without addition of cyanide. Such oscillations may be
      induced if argon or another inert gas is bubbled through the yeast cell
      suspension. This supports that the synchronizing agent is a volatile compound
      secreted by the yeast cells, e.g. CO2 and/or acetaldehyde. Our results show that
      the rate of acetaldehyde removal is not a crucial parameter to the
      synchronization of the yeast cells. The sample cell was connected to a membrane
      inlet mass spectrometer (MIMS) for online determination of extracellular non
      polar compounds. Oscillations in the secretion of CO2 were detected using the
      MIMS.

PMID- 15251207
TI  - Characterization of a thermophilic DNA ligase from the archaeon Thermococcus
      fumicolans.
AB  - A PCR protocol was used to identify and sequence a gene encoding a DNA ligase
      from Thermococcus fumicolans (Tfu). The recombinant enzyme, expressed in
      Escherichia coli BL21(DE3) pLysS, was purified to homogeneity and characterized.
      The optimum temperature and pH of Tfu DNA ligase were 65 degrees C and 7.0,
      respectively. The optimum concentration of MgCl2, which is indispensable for the
      enzyme activity, was 2 mM. We showed that Tfu DNA ligase displayed nick joining
      and blunt-end ligation activity using either ATP or NAD+, as a cofactor. In
      addition, our results would suggest that Tfu DNA ligase is likely to use the same
      catalytic residues with the two cofactors. The ability for DNA ligases, to use
      either ATP or NAD+, as a cofactor, appears to be specific of DNA ligases from
      Thermococcales, an order of hyperthermophilic microorganisms that belongs to the
      euryarchaeotal branch of the archaea domain.

PMID- 15251208
TI  - Three fur homologues from Anabaena sp. PCC7120: exploring reciprocal protein
      promoter recognition.
AB  - DNA sequence analysis of the Anabaena sp. PCC7120 genome confirmed the presence
      of three open reading frames (all1691, all2473 and alr0957) containing the
      histidine-rich region characteristic of the Fur family. The genes coding for the
      three Fur proteins were cloned and overexpressed in Escherichia coli. The
      overexpression products, called FurA, FurB and FurC are only distantly related.
      The ability of the three recombinant proteins to bind iron-boxes identified in
      the three fur promoter regions was tested by electrophoretical mobility shift
      assays. FurA binds the three fur promoters with increased affinity in presence of
      metal. FurB also binds the three fur promoters, and its affinity is increased
      with DTT. FurC does not bind to furA or furB promoter regions or to its own
      promoter. However, FurC affects the ability of FurB and FurA to bind their target
      promoters.

PMID- 15251209
TI  - Gene cloning, expression and characterization of novel phytase from
      Obesumbacterium proteus.
AB  - The gene phyA encoding phytase was isolated from Obesumbacterium proteus genomic
      library and sequenced. The cleavage site of the PhyA signal peptide was predicted
      and experimentally proved. The PhyA protein shows maximum identity of 53% and 47%
      to phosphoanhydride phosphorylase from Yersinia pestis and phytase AppA from
      Escherichia coli, respectively. Based on protein sequence similarity of PhyA and
      its homologs, the phytases form a novel subclass of the histidine acid
      phosphatase family. To characterize properties of the PhyA protein, we expressed
      the phyA gene in E. coli. The specific activity of the purified recombinant PhyA
      was 310 U mg(-1) of protein. Recombinant PhyA showed activity at pH values from
      1.5 through 6.5 with the optimum at 4.9. The temperature optimum was 40-45
      degrees C at pH 4.9. The Km value for sodium phytate was 0.34 mM with a Vmax of
      435 U mg(-1).

PMID- 15251211
TI  - Over-production of dihydrofolate reductase leads to sulfa-dihydropteroate
      resistance in yeast.
AB  - Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa
      dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with
      dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the
      target of sulfa-DHP. The effect of over-production of DHFR on sulfa-DHP
      resistance was examined in Saccharomyces cerevisiae using a strain that requires
      DHF for growth. This strain was transformed with a plasmid which encodes over
      production of DHFR in the presence of CuSO4. Over-production led to resistance to
      sulfa-DHP suggesting that sulfa-DHP targets DHFR. Spontaneous mutants hyper
      resistant to sulfa-DHP did not show any changes within DHFR.

PMID- 15251210
TI  - Construction of a recA mutant of Azospirillum lipoferum and involvement of recA
      in phase variation.
AB  - The plant-growth promoting rhizobacterium Azospirillum lipoferum strain 4B
      generates in vitro a stable phase variant designated 4VI at frequencies of 10(-4)
      to 10(-3) per cell per generation. Variant 4VI displays pleitropic modifications,
      such as the loss of swimming motility and the inability to assimilate certain
      sugars compared to the wild type. The mechanism underlying phase variation is
      unknown. To determine whether RecA-mediated processes are involved in phase
      variation, the recA gene of A. lipoferum 4B was cloned and sequenced and a recA
      mutant (termed 4BrecA) was constructed by allelic exchange. Strain 4BrecA showed
      increased sensitivity to UV and MMS compared with 4B and impaired recombinase
      activity. The ability to generate variants in vitro was not altered; the variants
      from 4BrecA exhibited all morphological and biochemical features characteristic
      of the variant generated by strain 4B. However, the frequency of variants
      generated by 4BrecA was increased by up to 10-fold. So, in contrast with many
      studies showing the abolition or a large reduction of the frequency of phase
      variation in recA mutants, this study describes an enhancement of phase variation
      in the absence of a functional recA.

PMID- 15251212
TI  - The mannitol cycle in Pleurotus ostreatus (Florida).
AB  - In mushroom, presence of the mannitol cycle has not been reported so far although
      the polyol is supposed to be generated by the reduction of fructose by mannitol
      dehydrogenase. This study submits evidence for the presence of the mannitol cycle
      in Pleurotus ostreatus. The key enzyme of the cycle, mannitol-1-phosphate
      dehydrogenase (M1PDH), was present appreciably in all the developmental stages of
      the mushroom. However, the enzyme level dropped significantly at the onset of
      sporulation. The presence of M1DPH was confirmed by isozyme analysis and RT-PCR
      mediated amplification of a approximately 400 bp DNA fragment.

PMID- 15251213
TI  - A kinetic model for Xylella fastidiosa adhesion, biofilm formation, and
      virulence.
AB  - Xylella fastidiosa is the causal agent of citrus variegated chlorosis and
      Pierce's disease which are the major threat to the citrus and wine industries.
      The most accepted hypothesis for Xf diseases affirms that it is a vascular
      occlusion caused by bacterial biofilm, embedded in an extracellular translucent
      matrix that was deduced to be the exopolysaccharide fastidian. Fourier transform
      infrared spectroscopy analysis demonstrated that virulent cells which form
      biofilm on glass have low fastidian content similar to the weak virulent ones.
      This indicates that high amounts of fastidian are not necessary for adhesion. In
      this paper we propose a kinetic model for X. fastidiosa adhesion, biofilm
      formation, and virulence based on electrostatic attraction between bacterial
      surface proteins and xylem walls. Fastidian is involved in final biofilm
      formation and cation sequestration in dilute sap.

PMID- 15251214
TI  - Evidence for non-ribosomal peptide synthetase production of cereulide (the emetic
      toxin) in Bacillus cereus.
AB  - Little is known about the process whereby the emetic toxin (or cereulide) of
      Bacillus cereus is produced. Two cereulide-producing strains of B. cereus were
      cloned and sequenced following polymerase chain reaction (PCR) amplification with
      primers that were specific for conserved regions of non-ribosomal peptide
      synthetase (NRPS) genes. The cloned regions of the B. cereus strains were highly
      homologous to conserved regions of other peptide synthetase nucleotide sequences.
      Primers were designed for two variable regions of the NRPS gene sequence to
      ensure specificity for the emetic strains. A total of 86 B. cereus strains of
      known emetic or non-emetic activity were screened using these primers. All of the
      emetic strains (n=30) displayed a 188 bp band following amplification and gel
      electrophoresis. We have developed an improved method of identifying emetic
      strains of B. cereus and provided evidence that cereulide is produced by peptide
      synthetases.

PMID- 15251215
TI  - Cloning, expression, and fibrin (ogen)olytic properties of a subtilisin DJ-4 gene
      from Bacillus sp. DJ-4.
AB  - Previously, we purified a strong fibrinolytic enzyme (subtilisin DJ-4) from
      Bacillus sp. DJ-4 and characterized its enzymatic activity. Here, we cloned the
      gene subtilisin DJ-4, and determines its nucleotide sequence, which showed 97%
      identity with subtilisin BPN' from B. amyloliquefacens. Recombinant full
      subtilisin DJ-4 (rf-subDJ-4) and mature-subtilisin DJ-4 (rm-subDJ-4) were
      expressed using a pET29 vector system, and their fibrin (ogen)olytic and
      plasminogen activator activities were studied. rf-subDJ-4 was found to have a
      higher stability to heat (60 degrees C) and to acidic conditions (pH 3.0-4.0)
      than the native subtilisin DJ-4 of Bacillus sp. DJ-4. The plasminogen activator
      activity of rf-subDJ-4 was 2.75 times greater than that of plasmin on a molar
      basis. And its specific activity (F/C, the ratio of fibrinolytic activity to
      caseinolytic activity) was 2.67 and 3.97 times higher than those of subtilisin
      BPN' and subtilisin Carlsberg, respectively. rf-subDJ-4 rapidly hydrolyzed the
      Aalpha-, Bbeta-, and gamma-chains of fibrinogen within 5 min. But, unlike
      subtilisin BPN' at a very low concentration (50 ng), the gamma-chain was not
      cleaved. On the other hand, rm-subDJ-4 did not show enzyme activity.

PMID- 15251216
TI  - Novel protein domains and motifs in the marine planctomycete Rhodopirellula
      baltica.
AB  - The planctomycetes are a phylum of bacteria that have a unique cell
      compartmentalisation and yeast-like budding cell division and peptidoglycan-less
      proteinaceous cell walls. We wished to further our understanding of these unique
      organisms at the molecular level by searching for conserved amino acid sequence
      motifs and domains in the proteins encoded by Rhodopirellula baltica. Using BLAST
      and single-linkage clustering, we have discovered several new protein domains and
      sequence motifs in this planctomycete. R. baltica has multiple members of the
      newly discovered GEFGR protein family and the ASPIC C-terminal domain family,
      whilst most other organisms for which whole genome sequence is available have no
      more than one. Many of the domains and motifs appear to be restricted to the
      planctomycetes. It is possible that these protein domains and motifs may have
      been lost or replaced in other phyla, or they may have undergone multiple
      duplication events in the planctomycete lineage. One of the novel motifs probably
      represents a novel N-terminal export signal peptide. With their unique cell
      biology, it may be that the planctomycete cell compartmentalisation plan in
      particular needs special membrane transport mechanisms. The discovery of these
      new domains and motifs, many of which are associated with secretion and cell
      surface functions, will help to stimulate experimental work and thus enhance
      further understanding of this fascinating group of organisms.

PMID- 15251217
TI  - Global expression analysis of two-component system regulator genes during
      Mycobacterium tuberculosis growth in human macrophages.
AB  - In the Mycobacterium tuberculosis H37Rv genome, there are 11 paired two-component
      regulatory system genes, two orphan histidine kinase genes, and six orphan
      response regulator genes. Expression of the 17 response regulator genes and the
      two orphan histidine kinase genes during growth of M. tuberculosis in human
      peripheral blood monocyte-derived macrophages has been analyzed by using cDNA
      mixtures prepared by the selective capture of transcribed sequences (SCOTS)
      technique. SCOTS probes were prepared from cDNA obtained from M. tuberculosis
      grown for 18, 48, and 110 h in human macrophages. Based on expression profiles,
      the regulatory genes were assigned to three categories: (i) constitutively
      expressed during growth in macrophages (three genes); (ii) differentially
      expressed during growth in macrophages (nine genes) and (iii) no detectable
      expression during growth in macrophages (seven genes).

PMID- 15251218
TI  - Fluorescence resonance energy transfer (FRET) based molecular detection of a
      genetically modified PCB degrader in soil.
AB  - Genetic analysis of the location of a mini-Tn5 promoted insertion of the LB400
      bph operon in the rhizosphere coloniser Pseudomonas fluorescens F113rifPCB,
      allowed the development of a specific PCR detection system based on the unique
      DNA sequence at this insertion site. Real time PCR using both SYBR green
      chemistry and Fluorescence Resonance Energy Transfer probes allowed the precise
      identification of the recombinant strain and its quantitative detection in soil
      microcosms over a (bacteria/g) range of five orders of magnitude. This new assay
      can detect the genetically modified microorganism from soil in less than 90 min
      and at levels below the detection limits of standard PCR or cultivable counts on
      selective media.

PMID- 15251219
TI  - Exploring the links between natural resource use and biophysical status in the
      waterways of the North Rupununi, Guyana.
AB  - The North Rupununi District in south-west Guyana is comprised of a mosaic of
      ecosystems, including savannas, wetlands and forests, and is home to the Makushi
      Amerindians, who depend on the waterways for their subsistence needs. With
      logging and mining seen as increasing threats to the region, it is necessary to
      look at methods for engaging stakeholders in monitoring the status of their
      natural resources. This paper presents the results of a pilot study carried out
      to investigate water use by the Makushi Amerindians, and collect baseline data on
      the hydro-morphological aspects of the waterways. Methods included informal
      interviews, the use of the River Habitat Survey (RHS), and water quality
      measurements. The results indicate the heavy reliance of the Makushi on the
      waterways for their daily lives, particularly on fishing. Although ponds and
      creeks are important sources of fish, the rivers provide much larger catches of a
      greater diversity of fish species, both in the wet and dry seasons. The physical
      characteristics of the water sources used by the Makushi are mainly associated
      with the surrounding habitat types: the savanna areas containing the more
      nutrient rich white-water rivers, and the tropical forest areas containing the
      less nutrient rich black-water rivers. This study indicates that at present there
      is no direct evidence of adverse impacts on the waterways used by the Makushi in
      terms of fish catches, habitat conditions and water quality. A monitoring scheme
      was set up using this study's outputs as a baseline from which any future changes
      can be compared. Further work is to be carried out over the next three years to
      produce monitoring and sustainable management procedures for the North Rupununi
      ecosystems, by linking the physical attributes of the environment to biodiversity
      and subsequently local livelihoods, and by building capacity of local
      stakeholders through training.

PMID- 15251220
TI  - A systems approach for the development of a sustainable community--the
      application of the sensitivity model (SM).
AB  - Corresponding to the concept of 'Think globally, act locally and plan regionally'
      of sustainable development, this paper discusses the approach of planning a
      sustainable community in terms of systems thinking. We apply a systems tool, the
      sensitivity model (SM), to build a model of the development of the community of
      Ping-Ding, located adjacent to the Yang-Ming-Shan National Park, Taiwan. The
      major issue in the development of Ping-Ding is the conflict between environmental
      conservation and the development of a local tourism industry. With the
      involvement of local residents, planners, and interest groups, a system model of
      26 variables was defined to identify characteristics of Ping-Ding through pattern
      recognition. Two scenarios concerning the sustainable development of Ping-Ding
      are simulated with interlinked feedbacks from variables. The results of the
      analysis indicate that the development of Ping-Ding would be better served by the
      planning of agriculture and the tourism industry. The advantages and shortfalls
      of applying SM in the current planning environment of Taiwan are also discussed
      to conclude this paper.

PMID- 15251221
TI  - Cost-effective control of SO2 emissions in Asia.
AB  - Despite recent efforts to limit the growth of SO(2) emissions in Asia, the
      negative environmental effects of sulphur emissions are likely to further
      increase in the future. This paper presents an extension of the RAINS-Asia
      integrated assessment model for acidification in Asia with an optimisation
      routine that can be used to identify cost-effective emission control strategies
      that achieve environmental targets for ambient SO(2) concentrations and sulphur
      deposition at least costs. Example scenarios developed with this optimisation
      module demonstrate a potential for significant cost savings in Asia, if emission
      controls are allocated to those sources that have the largest environmental
      impact and are cheapest to control. It is shown that strategies that
      simultaneously address harmful population exposure and the risk of vegetation
      damage from acid deposition result in the most cost-effective use of resources
      spent for emission controls.

PMID- 15251222
TI  - Predicting the distribution of ground beetle species (Coleoptera, Carabidae) in
      Britain using land cover variables.
AB  - Predictions of plant and animal species distributions are important for
      conservation and for the assessment of large-scale ecosystem change. Land cover
      data are becoming more widely available for use in land management and
      conservation. We use a logistic regression modelling approach to investigate the
      utility of these data for modelling. The relationship between the distribution of
      137 British ground beetles species and land cover was investigated using data
      from 1,687 10 km national grid squares. Land cover data were simplified using
      ordination and the axes used as predictors in logistic regression with presence
      absence data for individual beetle species as response variables. Significant
      regression models were generated for all species with first and second axis
      scores. The amounts of variation explained by models were generally low, but
      predictions derived from models generally matched the known distributions of the
      species in Britain. Species with coastal preferences were poorly modelled and
      predicted to occur throughout lowland Britain whilst a number of species
      occurring in southern Britain were predicted to occur into Scotland. A validation
      exercise comparing model predictions with new data from a survey of 59 10 km(2)
      produced mixed results with the distribution of grassland species being better
      predicted than riverine species. Jack-knifing was used to assess the robustness
      of models for four species which differed in their apparent responses to the land
      cover variables. Methods for improving the predictive power of these models and
      their potential for use in assessing the impact of global climate change are
      discussed.

PMID- 15251223
TI  - Upflow column reactor design for dechlorination of chlorinated pulping wastes by
      Penicillium camemberti.
AB  - A Penicillium camemberti strain isolated in our laboratory has been studied for
      its ability to degrade chlorinated pulping wastes, presumably containing a
      variety of chlorinated polyphenols. In batch tests, the highest removals (76%
      AOX, 61% color and 65% TOC) were obtained with 0.2 g/l feed acetate
      concentration. The tendency of the fungus to dechlorinate bleachery effluents
      better under non-shaking conditions and to attach onto surfaces suggested the use
      of immobilized cells rather than freely suspended ones in further exploitation of
      the process. An upflow glass wool packed column reactor established with this
      fungus could be operated for nearly two years in the laboratory. At best around
      70% AOX could be removed from chlorinated pulping wastes in 7.3 h of contact with
      no aeration and with a minimal amount of carbon supplement (0.2 g/l). Finally, an
      asymptotic mathematical formula for determining Michaelis-Menten kinetic rates
      has been derived. The kinetic rates K(m) (the Michaelis constant or saturation
      constant for the substrate) and V(m) (the product of maximum rate for the
      enzymatic reaction and biomass concentration) were then calculated as 126.386
      mg/l and 2.83017 mg/lh, respectively.

PMID- 15251224
TI  - Practical determination of the rheological behavior of pasty biosolids.
AB  - In this paper, we demonstrate that the rheological behavior of pasty sewage
      sludges, regardless of origin, treatment or composition, follows a Herschel
      Bulkley model. The yield stress and solid volume fraction are found to be the
      only two distinctive rheological characteristics of these materials. By scaling
      the shear rate and the shear stress with two parameters depending only on the
      yield stress and the solid fraction, the flow curves of 48 pasty sludges all fall
      along a unique dimensionless master curve. This result may be used in practice to
      determine, from simple, independent measurements, the rheological behavior of any
      pasty sludge: the yield stress can be measured with the help of the 'slump test'
      and the solid concentration determined from the organic and mineral matter
      contents. The results obtained with this technique are in very good agreement
      with those obtained by direct rheometry.

PMID- 15251225
TI  - An analysis of the environmental health impact of the Barekese Dam in Kumasi,
      Ghana.
AB  - Although dams have beneficial effects, they are also acknowledged as having
      serious environmental repercussions if they are not properly managed. The
      objective of this work was to examine the impact of the Barekese Dam in Ghana on
      the health status of three riparian communities downstream against a control. The
      environmental health status of the communities was analysed with reference to
      traditional endemic communicable water-related diseases in the catchment area,
      which were identified as malaria, urinary schistosomiasis, infectious hepatitis,
      diarrhoeal diseases and scabies. Case-control study was then conducted in the
      three phases of the dam (pre-construction, at the end of the construction and in
      the late operational phases) to analyse the health status of the communities as a
      function of the phases of the dam. The results showed that the control community
      consistently had a much better health status than two of the riparian
      communities, which were closer to the dam in all the three phases. However, it
      had a better health status than the third riparian community, which was farthest
      downstream, only in the first two phases. This community maintained a fairly
      constant health status retrospectively and did not appear to have been affected
      by the presence of the dam. On contrary, the health status of the two communities
      in close proximity to the dam deteriorated in the late operational phase. The
      study therefore showed that there was a strong association between the presence
      of the dam and poorer health status of the downstream communities in close
      proximity to it.

PMID- 15251226
TI  - Selective histamine H3 receptor antagonists for treatment of cognitive
      deficiencies and other disorders of the central nervous system.
AB  - Evidence exists to implicate the monoamine histamine in the control of arousal
      and cognitive functions. Antagonists of H(3) receptors are postsynaptic and
      presynaptic modulators of neural transmission in a variety of neuronal circuits
      relevant to cognition. Accumulating neuroanatomical, neurochemical,
      pharmacological, and behavioral data support the idea that H(3) receptor
      antagonists may function to improve cognitive performances in disease states
      (e.g., Alzheimer's disease and mild cognitive impairment states). Thus, H(3)
      receptor antagonists have been shown to increase performance in attention and
      memory tests in nonhuman experiments and prevent the degradation in performances
      produced by scopolamine, MK-801, or age. In contrast, agonists of the H(3)
      receptor generally produce cognitive impairing effects in animal models. The role
      of H(3) receptors in these behavioral effects is substantiated by data indicating
      a central origin for their effects, the selectivity of some of the H(3) receptor
      antagonists studied, and the pharmacological modification of effects of H(3)
      receptor antagonists by selective H(3) receptor agonists. Data and issues that
      challenge the potential role for H(3) receptor antagonists in cognitive processes
      are also critically reviewed. H(3) receptor antagonists may also have therapeutic
      value in the management of obesity, pain, sleep disorders, schizophrenia, and
      attention deficit hyperactivity disorder.

PMID- 15251227
TI  - Molecular mechanisms of ligand binding, signaling, and regulation within the
      superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis
      approaches to receptor structure and function.
AB  - The superfamily of G-protein-coupled receptors (GPCRs) could be subclassified
      into 7 families (A, B, large N-terminal family B-7 transmembrane helix, C,
      Frizzled/Smoothened, taste 2, and vomeronasal 1 receptors) among mammalian
      species. Cloning and functional studies of GPCRs have revealed that the
      superfamily of GPCRs comprises receptors for chemically diverse native ligands
      including (1) endogenous compounds like amines, peptides, and Wnt proteins (i.e.,
      secreted proteins activating Frizzled receptors); (2) endogenous cell surface
      adhesion molecules; and (3) photons and exogenous compounds like odorants. The
      combined use of site-directed mutagenesis and molecular modeling approaches have
      provided detailed insight into molecular mechanisms of ligand binding, receptor
      folding, receptor activation, G-protein coupling, and regulation of GPCRs. The
      vast majority of family A, B, C, vomeronasal 1, and taste 2 receptors are able to
      transduce signals into cells through G-protein coupling. However, G-protein
      independent signaling mechanisms have also been reported for many GPCRs. Specific
      interaction motifs in the intracellular parts of these receptors allow them to
      interact with scaffold proteins. Protein engineering techniques have provided
      information on molecular mechanisms of GPCR-accessory protein, GPCR-GPCR, and
      GPCR-scaffold protein interactions. Site-directed mutagenesis and molecular
      dynamics simulations have revealed that the inactive state conformations are
      stabilized by specific interhelical and intrahelical salt bridge interactions and
      hydrophobic-type interactions. Constitutively activating mutations or agonist
      binding disrupts such constraining interactions leading to receptor conformations
      that associates with and activate G-proteins.

PMID- 15251228
TI  - The quest for new cysteinyl-leukotriene and lipoxin receptors: recent clues.
AB  - The metabolism of arachidonic acid via the 5-lipoxygenase enzymatic pathway leads
      to the formation of the cysteinyl-leukotrienes and lipoxins, which have been
      implicated in several inflammatory reactions. While these lipid mediators are
      responsible for a variety of effects, their actions occur through the activation
      of 3 specific types of cloned receptors (i.e., CysLT(1), CysLT(2), and ALX).
      Although receptor activation can explain several biological actions associated
      with the mediators, there is some evidence to suggest that not all responses fit
      the well-known characteristics of these cloned receptors. Other receptor subtypes
      may also exist. Interestingly, the indirect evidence for support of this
      observation is principally derived from work performed on either blood elements
      and/or vascular smooth muscle. Because the initiating events associated with
      inflammation are essentially of vascular origin, further work at the molecular
      level may be necessary to confirm the data, which do not fit the well-known CysLT
      and ALX receptor profiles.

PMID- 15251229
TI  - A paucity of structural integrity in cloned porcine blastocysts produced in
      vitro.
AB  - The structural integrity of blastocyst stage embryos, consisting of the inner
      cell mass (ICM) and trophectoderm (TE) cells, is a prerequisite for normal
      development after implantation in mammals. In this study, allocation of nuclear
      transfer (NT)-derived porcine blastocysts to the ICM and to the TE cells was
      examined and compared with IVF- and in vivo-derived embryos. NT-derived embryos
      had a lower developmental competence to the blastocyst stage than IVF-derived
      embryos (P < 0.05). Total cell number of NT-derived blastocysts was inferior to
      that of IVF-derived embryos (P < 0.05), although no difference was detected
      between the two groups in the ratio of ICM to total cells. However, in vivo
      derived blastocysts had a higher proportion of ICM to total cells compared with
      in vitro-produced embryos (P < 0.01). To investigate what proportions of in vitro
      produced porcine embryos represent normal structural integrity, differentially
      stained blastocysts were individually classified into three presumptive groups
      (I: <20%; II: 20-40%; III: >40%) according to the ratio of ICM to total cells.
      Low proportions of NT- (12.5%, 7/56) and IVF-derived blastocysts (15.8%, 9/57)
      were assigned to Group II, presumptively having a normal range of structural
      integrity, whereas, almost all in vivo-derived embryos (97.5%, 39/40) were
      allocated to Group II. In conclusion, limited structural integrity may lead to
      the poor survival to term of NT- or IVF-derived porcine embryos produced in
      vitro.

PMID- 15251230
TI  - Comparative study of the reproductive characteristics of XY male and hormonally
      sex-reversed XX male Eurasian perch, Perca fluviatilis.
AB  - In order to compare the reproductive capacity of XY male versus XX male
      (neomales) Eurasian perch (Perca fluviatilis), we determined the sperm quality
      (sperm concentration and motility) and reproductive characteristics such as
      gonadosomatic index (GSI), fertilization rate and sex steroid levels
      (testosterone, T; 17beta-estradiol, E2 and 11-ketotestosterone, 11KT) during the
      reproductive season. Median GSI was not significantly different between XY males
      (7.9%) and XX males (7.5%). Fertilization rates ranged between 30.0 and 98.0%.
      Sperm concentration ranged between 27.9 x 10(9) and 42.0 x 10(9) spermatozoa ml(
      1). Median level of T, 11KT and E2 levels increased in the middle of the
      reproductive season (2136.0, 2409.0 and 3252.0 pg ml(-1), respectively) and
      decreased at the end (1657.0, 2006.6 and 431.0 pg ml(-1), respectively). Sperm
      motility was assessed by CASA and expressed by the curvilinear velocity (VCL),
      straight line velocity (VSL), average path velocity (VAP), linearity (LIN),
      percentage of motile sperm (% MOT) and motile concentration (MOC). Overall, there
      were not any significant differences between XY and XX males. In conclusion, no
      differences of reproductive capacities were observed between XY males and XX
      males suggesting that the last can be crossed with females to improve the
      productivity of Eurasian perch by producing all-female stock.

PMID- 15251231
TI  - Seminal plasma proteins prolong the viability of rainbow trout (Oncorynchus
      mykiss) spermatozoa.
AB  - Rainbow trout (Oncorhynchus mykiss) spermatozoa were incubated in artificial
      sperm motility inhibiting saline solution (SMIS), in SMIS containing seminal
      plasma proteins or in pure seminal plasma. In SMIS containing the total seminal
      plasma protein fraction or the <50 kDa protein fraction or in pure seminal
      plasma, significantly higher motility rates and swimming velocities could be
      activated than in SMIS without seminal plasma proteins and in SMIS containing the
      >50 kDa protein fraction. These preliminary results indicated that seminal plasma
      proteins have physiological functions in prolongation and stabilization of sperm
      viability when using sperm motility as viability index.

PMID- 15251232
TI  - Effects of the supplementation of trehalose extender containing egg yolk with
      sodium dodecyl sulfate on the freezability of goat spermatozoa.
AB  - Two experiments were conducted to determine the effect of sodium dodecyl sulfate
      (SDS) added to a trehalose-egg yolk extender on the cryopreservation of goat
      spermatozoa. In Experiment 1, semen from four goats was frozen in trehalose
      extender (osmolality = 370, pH = 7) containing 4 and 20% (v/v) glycerol and egg
      yolk, respectively, and 0.035-0.2% SDS. After thawing, sperm motility and
      acrosome integrity were assessed using a computer-assisted sperm analysis (CASA)
      system and fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA).
      Both motility and progressive motility were improved (P < 0.05) by increasing the
      concentration of SDS in the trehalose-egg yolk extender, with the best results
      obtained with SDS at 0.1% (80.0 +/- 1.5% and 65.0 +/- 1.7%, respectively). There
      were no significant differences in path velocity when spermatozoa were frozen in
      a diluent containing 0.035, 0.05, 0.075, or 0.1% SDS, but path velocity decreased
      significantly with 0.2% SDS. The percentage of acrosome-intact sperm were highest
      (P < 0.05) when 0.05% (74.0 +/- 1.1) and 0.075% (70.0 +/- 1.2) SDS were used. In
      Experiment 2, the effect of diluent storage time (6, 24, or 48 h) before freezing
      on the cryoprotective effect of SDS was investigated. Prolonged storage of the
      diluent had slight cryoprotective effects when 0.2% SDS is used, while motility
      and the acrosome integrity of the cryopreserved spermatozoa improved slightly
      when the extender was stored for 48 h at 5 degrees C before use. In conclusion,
      goat sperm freezability was significantly improved when sperm were frozen in a
      trehalose-egg yolk extender containing an adequate concentration of SDS.

PMID- 15251233
TI  - Effects of heparin and sperm concentration on cleavage and blastocyst development
      rates of bovine oocytes inseminated with flow cytometrically-sorted sperm.
AB  - The objective was to determine the optimal concentration of heparin for sperm
      capacitation, as well as the optimal sperm concentration for in vitro
      fertilization using flow cytometrically-sorted sperm from individual bulls. A
      total of 5327 bovine oocytes and sperm from four bulls were examined. Oocytes
      from slaughterhouse ovaries were matured in TCM199 for 22-24 h. Flow
      cytometrically-sorted sperm as well as unsorted control sperm from the same bulls
      were cryopreserved. For sperm from each of the four bulls, oocytes were
      inseminated in a three-by-three factorial design plus one control group (three
      heparin concentrations: 0, 2, and 10 microg/ml and three sperm concentrations:
      0.5 x 10(6), 1.5 x 10(6), and 4.5 x 10(6) ml(-1); 10 microg/ml of heparin and 1.5
      x 10(6) ml(-1) of sperm were used for the unsorted control). Presumptive zygotes
      were cultured in chemically defined media, CDM-1 and CDM-2 for 52-54 h and 96 h,
      respectively. Samples of about 10 oocytes from each of the 10 treatment groups
      per replicate were fixed at 18-20 h after insemination to determine sperm
      pronuclei formation and polyspermy. Increased polyspermy resulted as heparin and
      sperm concentrations increased (P < 0.05). A higher rate of polyspermy was found
      in oocytes inseminated with unsorted control sperm compared with sorted sperm (P
      < 0.05). Sperm of one of four bulls tested required no heparin and lower
      concentration (0.5 x 10(6) ml(-1)) to obtain optimal cleavage and blastocyst
      rates while optimal parameters for another bull were higher heparin (10
      microg/ml) and sperm concentrations (4.5 x 10(6) ml(-1)). Optimal parameters for
      the other two were intermediate levels of heparin and sperm. Sperm appeared to be
      partially capacitated during the flow cytometric-sorting process used for sex pre
      determination. When heparin and sperm concentrations were optimized for
      individual bulls, blastocyst production per oocyte was similar for sorted and
      unsorted sperm for three of the four bulls studied.

PMID- 15251234
TI  - Effects of a new injectable short-term release deslorelin in foal-heat mares.
AB  - Mares treated with subcutaneous deslorelin implants on the first postpartum
      estrus early in the breeding season had significant reductions in the number of
      large follicles at early pregnancy examinations and delayed return to estrus (in
      mares that failed to become pregnant); these adverse effects were attributed to a
      prolonged release of the drug from the implant. In 2003, an injectable short-term
      release (<24 h) deslorelin product became available. The objective of this study
      was to determine if this product would hasten ovulation in early foaling first
      postpartum estrus mares without reducing the number of large follicles at early
      pregnancy examination (14-15 days postovulation). Beginning 5-6 days postpartum,
      first postpartum estrus (foal-heat) mares were teased daily and examined thrice
      weekly (Tuesday, Thursday and Saturday) by transrectal ultrasonography. Mares in
      estrus with a follicle > or = 34 mm diameter on Tuesdays or Thursdays were
      alternately assigned to: Treatment 1, n = 17; 1.5 mg injectable short-term
      release deslorelin, or Treatment 2, n = 16; Control (no treatment). The schedule
      allowed accurate determination of the number of mares ovulating within 2 days of
      treatment (i.e., ovulations detected on Thursday or Saturday). Mares were mated
      on the day of treatment and at 2-day intervals until either ovulation was
      confirmed or until behavioral estrus ceased. Transrectal ultrasonography was done
      14-15 days after ovulation to assess ovarian follicles and pregnancy status.
      Fewer covers were required and more mares ovulated within 2 days of treatment in
      deslorelin-treated versus Control mares (P < 0.01). Pregnancy rates were normal
      (69%) in deslorelin-treated mares. The number of large follicles 14-15 days after
      ovulation did not differ between deslorelin-treated and Control mares (P > 0.10),
      suggesting follicular suppression did not occur with this formulation of
      deslorelin.

PMID- 15251235
TI  - A sheer pharmacologic approach to compare the contractile effects of PGF2alpha,
      DL-cloprostenol and D-cloprostenol on isolated uterine, tracheal, ileal and
      arterial smooth muscle preparations.
AB  - The contractile effects of PGF2alpha and its cloprostenol analogs (D-enantiomer
      and racemate) were examined on isolated smooth muscle preparations (uterine,
      tracheal, ileal and arterial) from rat, guinea-pig and horse. DL- and D
      cloprostenol were potent contractors of myometrium, but had negligible secondary
      effects on other types of smooth muscle, except artery whose response to the D
      enantiomer may give rise to some concern.

PMID- 15251236
TI  - Hormonal induction of ovulation and artificial insemination in suckled beef cows
      under nutritional stress.
AB  - The objective was to develop a program for inducing estrus (followed by
      insemination) of suckled beef cows under nutritional stress (poor body
      condition). A total of 123 cows, from 60 to 75 days postpartum, were classified
      according to their body condition score (BCS; range from 1 to 5, in increments of
      0.5) and allocated into two groups. On Day 0 (without regard to stage of the
      estrous cycle), cows (n = 59) in the hormone induction (HI) treatment group were
      given an intravaginal device (IVD) containing 250 mg of medroxiprogesterone
      acetate (MAP) and an i.m. injection of 2.5 mg estradiol benzoate (EB). On Day 6,
      these cows were given 500 IU eCG i.m. and calves were weaned for 96 h. The IVD
      were removed on Day 7. Cows detected in estrus by 45 h after IVD removal were
      inseminated 12 h after standing estrus; cows not in estrus by 45 h after IVD
      removal received an i.m. injection of 100 microg gonadorelin (GnRH) and were
      inseminated 16-18 h later. In the control group (C), cows (n = 64) only had their
      calves weaned at Day 6 (for 96 h), with estrus detection and AI from Days 6 to
      11. Overall, the BCS ranged from 2.0 to 3.0. In the treatment group, estrus and
      pregnancy rates in cows with BCS 2.0 (20 and 30%, respectively) was lower (P <
      0.05) than those with BCS 3.0 (50 and 66.6%, respectively), but did not differ (P
      > 0.05) from BCS 2.5 (23.3 and 47.6%). In C group, only 2 of 66 cows were
      detected in estrus and bred (neither was pregnant). In conclusion, the program
      for induction of ovulation using MAP, EB, eCG and GnRH increased the pregnancy
      rate in beef cows in poor body condition, enabling AI to be done in a 63-h
      interval.

PMID- 15251237
TI  - Effect of the timing of the first cleavage on the developmental potential of
      nuclear-transferred mouse oocytes receiving embryonic stem cells.
AB  - The present study examined whether the timing of the first cleavage has an effect
      on the in vitro and in vivo developmental potential of nuclear-transferred mouse
      oocytes receiving embryonic stem cells. First, the timing of the first cleavage
      and the developmental potential of nuclear-transferred oocytes were examined
      every hour from 12 to 24 h after the start of culture and compared with in vitro
      fertilized oocytes. The developmental potential of in vitro-fertilized oocytes
      decreased gradually according to the time required for cleavage (84% (32/38) for
      15 h to 50% (1/2) for 20 h), but intermediate-cleaved (15-16 h) nuclear
      transferred oocytes had a higher potential to develop into blastocysts (55%
      (17/31) to 67% (45/67) versus 0-43% (6/14)]. Second the nuclear-transferred
      oocytes were divided into three groups according to the timing of the first
      cleavage; each group was cultured to blastocysts in vitro, and then transferred
      to recipients. The potential of intermediate-cleaved oocytes (15-16 h) to develop
      into blastocysts was significantly higher than fast-cleaved (before 15 h) and
      slow-cleaved (after 16 h) oocytes (65, 46, and 37%). The proportion of fetuses on
      Day 10.5 of pregnancy was highest in the intermediate-cleaved group (4 versus 2
      and 1%, respectively) and a full-term fetus was obtained from this group. The
      present study demonstrated that the timing of the first cleavage could be used to
      determine the potential of nuclear-transferred oocytes with embryonic stem cells
      to develop to the blastocyst stage in vitro, but not to determine post
      implantation viability after transfer to recipients.

PMID- 15251238
TI  - Effects of treatment with LH or FSH from 4 to 8 weeks of age on the attainment of
      puberty in bull calves.
AB  - A transient increase in gonadotropin secretion between 6 and 20 weeks of age is
      critical for the onset of puberty in bull calves. To try and hasten the onset of
      puberty, bull calves were treated (s.c.) with 3 mg of bLH (n = 6) or 4 mg of bFSH
      (n = 6) once every 2 days, from 4 to 8 weeks after birth; control calves received
      saline (n = 6). At 4 and 8 weeks of age, mean LH concentrations were higher (P <
      0.05) in bLH-treated (2.3 +/- 0.04 ng/ml and 1.20 +/- 0.04 ng/ml) as compared to
      control calves (0.50 +/- 0.1 ng/ml and 0.70 +/- 0.10 ng/ml). Mean serum FSH
      concentrations at 4 and 8 weeks of age, were higher (P < 0.05) in bFSH-treated
      (1.60 +/- 0.20 ng/ml and 1.10 +/- 0.2 ng/ml) as compared to control calves (0.38
      +/- 0.07 ng/ml and 0.35 +/- 0.07 ng/ml). The age at which scrotal circumference
      (SC) first reached > or = 28 cm, occurred earlier (P < 0.05) in bFSH-treated
      calves as compared to saline-treated calves (39.3 +/- 1.3 and 44.8 +/- 1.3 weeks
      of age, respectively). Based on testicular histology at 56 weeks of age,
      treatment with bFSH resulted in greater (P < 0.05) numbers of Sertoli cells (5 +/
      0.2, 6 +/- 0.3 and 5 +/- 0.3 in bLH-, bFSH- and saline-treated calves,
      respectively); elongated spermatids (42 +/- 2, 57 +/- 8 and 38 +/- 5 in bLH-,
      bFSH- and saline-treated calves, respectively) and spermatocytes (31 +/- 3, 38 +/
      3 and 29 +/- 2 in bLH-, bFSH- and saline-treated calves, respectively) per
      seminiferous tubule. We concluded that treatment of bull calves with bFSH from 4
      to 8 weeks of age increased testicular growth (SC); hastened onset of puberty (SC
      > or = 28 cm); and enhanced spermatogenesis.

PMID- 15251239
TI  - Boar sperm storage capacity of BTS and Androhep Plus: viability, motility,
      capacitation, and tyrosine phosphorylation.
AB  - Androhep Plus, a long-term extender (up to 7 days) and Beltsville Thawing
      Solution (BTS), a short-term extender (up to 3 days), are commonly used for
      liquid storage of porcine semen. To test the hypothesis that modifications in
      sperm viability, motility, chlortetracycline (CTC) fluorescence patterns, and
      protein tyrosine phosphorylation occur during semen storage in extenders, we
      compared these end points at different periods of storage in either Androhep Plus
      or BTS. Sperm from five boars were assessed daily over 12 days of storage (n = 5
      ejaculates from different boars). Viability was not different (P < 0.05 between
      extenders, except on Day 2, when Androhep Plus maintained better viability.
      Differences in the percentage of motile (total) sperm due to extender were
      evident on Days 2, 4, 5, and 6, when Androhep Plus was superior to BTS (P <
      0.05). The percentages of progressively motile sperm also differed, with Androhep
      Plus supporting higher rates on Days 2, 4, 5, 7, 8, 9, 10, and 11 (P < 0.05). The
      CTC fluorescence pattern distribution differed due to extender as early as Day 2;
      storage in Androhep Plus induced higher levels of pattern B sperm (P < 0.05) than
      storage in BTS. A tyrosine-phosphorylated protein of Mr 21,000 appeared after 10
      days in sperm incubated in BTS, and was identified as a phospholipid
      hydroperoxide glutathione peroxidase. Therefore, modifications in viability,
      motility, CTC fluorescence patterns, and sperm protein tyrosine phosphorylation
      were apparent during sperm storage in extenders; these may affect the fertilizing
      capacity of the semen.

PMID- 15251240
TI  - Rapid sexing of bovine preimplantation embryos using loop-mediated isothermal
      amplification.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel DNA amplification method
      that amplifies a target sequence specifically under isothermal conditions. The
      product of LAMP is detected by the turbidity of the reaction mixture without
      electrophoresis. The objective of this study was to develop a rapid sexing method
      for bovine preimplantation embryos using LAMP. The first experiment was conducted
      to optimize the DNA extraction method for LAMP-based embryo sexing. The DNA of
      single blastomeres was extracted using three methods: heat, NaOH, and proteinase
      K-Tween 20 (PK-TW) treatments. Sexing was performed with two LAMP reactions, male
      specific and male-female common reaction, after DNA extraction. The rates of
      correct determination of sex were 88.9-94.4%, with no difference among methods.
      The sensitivity and accuracy of LAMP-based embryo sexing were evaluated in the
      next experiment. The proportion of samples in which the sex was correctly
      determined was 75-100% for one to five biopsied cells. Lastly, in vivo-derived
      embryos were examined to verify the usefulness of LAMP-based embryo sexing, and
      some of these fresh, sexed embryos were transferred into recipient animals. The
      time needed for sexing was <1 h. The pregnancy rate was 57.4% and all calves born
      were of the predicted sex (12 male and 21 female). Therefore, LAMP-based embryo
      sexing accurately determined gender and is suitable for field application.

PMID- 15251241
TI  - Ability to activate oocytes and chromosome integrity of mouse spermatozoa
      preserved in EGTA Tris-HCl buffered solution supplemented with antioxidants.
AB  - Potential methods for cryopreservation of mouse spermatozoa are freeze-drying,
      desiccation, and suspension in EGTA Tris-HCl buffered solution (ETBS: 50 mM NaCl,
      50 mM EGTA, and 10 mM Tris-HCl). To determine the duration that mouse spermatozoa
      suspended in ETBS-based solutions could retain their normal characteristics
      without freezing, spermatozoa collected from the cauda epididymis were suspended
      in ETBS or in ETBS supplemented with the antioxidants, dimethyl sulfoxide (DMSO),
      or DL-alpha-tocopherol acetate (Vitamin E acetate; VEA) diluted in DMSO, then
      held at ambient temperature (22-24 degrees C) for up to 9 days. When oocytes were
      injected with spermatozoa preserved in ETBS alone, activation rates of oocytes
      and chromosome integrity at the first cleavage metaphase decreased at 1 day (P <
      0.001) and 2-4 days (P < 0.01) following treatment. When oocytes were injected
      with spermatozoa preserved in ETBS supplemented with DMSO or VEA/DMSO, chromosome
      integrity did not decrease significantly (through 9 days of preservation).
      Although DMSO maintained sperm chromosome integrity more effectively than
      VEA/DMSO up to 2-4 days (91 and 67%, normal karyotypes in DMSO and VEA/DMSO,
      respectively), VEA/DMSO helped to maintain the ability of spermatozoa to activate
      oocytes, but did not enhance the maintenance of sperm chromosome integrity. These
      results suggested that deterioration of spermatozoa preserved in ETBS alone was
      delayed by supplementation with antioxidants.

PMID- 15251242
TI  - A comparison of a mechanical sector and a linear array transducer for ultrasound
      guided transvaginal oocyte retrieval (OPU) in the cow.
AB  - A comparison was made between a linear array and a mechanical multiple angle
      sector (MAP) transducer for ultrasound-guided transvaginal oocyte retrieval (ovum
      pick-up, OPU) in the cow. The ovaries of five dairy cows were punctured, in a
      twice-weekly OPU program lasting for 4 weeks, using two different 5.0-MHz
      transducers equipped with an identical disposable needle-guidance system. Both
      ovaries were visualized using each transducer before puncture and the number of
      follicles with a diameter of less than 5 mm (small) and with a diameter equal to
      or greater than 5 mm (large) was recorded. Subsequently, one ovary of the pair
      was punctured guided by the MAP, while the other was punctured using the linear
      array transducer. During the next puncture session on a given animal, the two
      systems were switched and used on the alternate ovary in a crossover design.
      Parameters assessed for each system were: the total number of follicles
      visualized in each diameter class, and the total number of retrieved oocytes per
      cow. A significant difference was found for the ability to visualize smaller
      follicles in favor of the MAP transducer, with an average visualization of 71.6
      +/- 30.3 small follicles per cow during the 4-week trial period, compared to 59.8
      +/- 25.7 for the linear array transducer (t-test for paired samples, P = 0.007).
      No differences were found in the visualization of large follicles. A numerically
      greater number of oocytes were retrieved using the MAP transducer, compared to
      the linear array, (averages of 14.2 +/- 7.2 versus 7.4 +/- 6.1, respectively),
      although these differences were not statistically significant. In conclusion,
      both systems can be effectively used for oocyte retrieval in the cow, however,
      the MAP transducer demonstrated superior visualization of small follicles.

PMID- 15251243
TI  - Effects of different artificial insemination techniques and sperm doses on
      fertility of normal mares and mares with abnormal reproductive history.
AB  - The effects of different artificial insemination (AI) techniques and sperm doses
      on pregnancy rates of normal Hanoverian breed mares and mares with a history of
      barrenness or pregnancy failure using fresh or frozen-thawed sperm were
      investigated. The material included 187 normal mares (148 foaling and 39 young
      maiden mares) and 85 problem mares with abnormal reproductive history. Mares were
      randomly allotted into groups with respect to AI technique (routine AI into the
      uterine body, transrectally controlled deep intracornual AI ipsilateral to the
      preovulatory follicle, or hysteroscopic AI onto the uterotubal junction
      ipsilateral to the preovulatory follicle), storage method of semen (fresh, frozen
      thawed), AI volume (0.5, 2, 12 ml), and sperm dose (50 x 10(6) or 300 x 10(6)
      progressively motile sperm (pms) for fresh semen and 100 or 800 x 10(6) frozen
      thawed sperm with >35% post-thaw motility). The mares were inseminated once per
      cycle, 24 h after hCG administration when fresh semen was used, or 30 h for
      frozen-thawed semen. Differences in pregnancy rates between treatment groups were
      analyzed by Chi-squared test, and for most relevant factors (insemination
      technique, mare, semen, and stallion) expectation values and confidence intervals
      were calculated using multivariate logistic models. Neither insemination
      technique, volume, sperm dose, nor mare or stallion had significant effects (P >
      0.05) on fertility. Type of semen, breeding mares during foal heat, and an
      interaction between insemination technique, semen parameters, and mares did have
      significant effects (P < 0.05). In problem mares, frozen semen AI yielded
      significantly lower pregnancy rates than fresh semen AI (16/43, 37.2% versus
      25/42, 59.5%), but this was not the case in normal mares. In normal mares,
      hysteroscopic AI with fresh semen gave significantly (P < 0.05) better pregnancy
      rates than uterine body AI (27/38, 71% versus 18/38, 47.3%), whereas in problem
      mares this resulted in significantly lower pregnancy rates than uterine body AI
      (5/15, 33.3% versus 16/19, 84.2%). Our results demonstrate that for problem
      mares, conventional insemination into the uterine body appears to be superior to
      hysteroscopic insemination and in normal mares, the highest pregnancy rates can
      be expected by hysteroscopic insemination.

PMID- 15251244
TI  - In vitro culture of epithelial cells from the caput, corpus, and cauda epididymis
      of Sus domesticus.
AB  - This work describes a protocol to culture epididymal epithelial cells from the
      caput, corpus, and cauda regions of Sus domesticus. Epididymal epithelial
      fragments were obtained by dissection and enzymatic digestion with collagenase.
      About 30 epididymal fragments from each epididymal region were cultured in 24
      well culture plates with supplemented RPMI-1640 medium at 37 degrees C, 5% CO2 in
      air, and 100% humidity. A confluent monolayer of polygonal and tightly packed
      epithelioid cells from the three epididymal regions was obtained after 12-16 days
      in culture and maintained in vitro for more than 60 days. The proportion of
      epididymal epithelial cells in these cultures was assessed by immunofluorescent
      staining for cytokeratins. Throughout the 2 months of culture, about 80% of the
      cells were cytokeratin-positive. Electron microscopy observations indicated that
      cultured cells from caput, corpus, and cauda epididymal regions were tightly
      adhered to each other by junctional complexes and that stereocilia were present
      in their apical membranes. Moreover, the presence of an extensive rough
      endoplasmic reticulum, Golgi apparatus and numerous vesicles in the cytoplasm
      suggested that cultured cells maintained secretory and absorptive activities.
      These results show that the epididymal epithelial cells in culture from S.
      domesticus retain some fundamental features that characterize the epididymal
      epithelium in the intact organ. This system might be a valuable tool for studying
      the mechanism of sperm maturation in vitro, including epididymal cell secretions
      and the analysis of regional differences.

PMID- 15251245
TI  - Ovarian follicle vascularization in fasted pig.
AB  - The authors have investigated in the different classes of ovarian follicles the
      vascular area, the blood vessel distribution, the vascular endothelial growth
      factor (VEGF) mRNA expression and the VEGF secretion during equine chorionic
      gonadotropin (eCG) induced follicle growth in prepubertal gilts fed ad libitum or
      fasted. Immunohistochemistry staining of Von Willebrand factor showed that
      fasting caused a dramatic increase in the vascular area of medium-large tertiary
      follicles. The increase involved the two concentric vessel networks and the area
      between them that, becoming crossed by several anastomosis, modified the whole
      vessel architecture. Both in situ hybridization and in vitro culture experiments
      demonstrate that granulosa cells from medium-large follicles are engaged in a
      copious VEGF production upon eCG stimulation both in gilts fed ad libitum or
      fasted. More surprisingly, the production of VEGF becomes diffuse amongst theca
      cells of fasted animals thus recruiting a compartment that in condition of normal
      feeding regimen appears nearly quiescent. In conclusion, the data presented
      describe a local angiogenic process that develops in the follicle wall of growing
      antral follicle in case of acute severe food restriction. The mechanism,
      essentially confined to follicles that potentially approach ovulation, appears to
      assume the meaning of a local compensatory mechanism that may help maintaining
      adequate nutrient delivery to follicles that undergo ovulation.

PMID- 15251246
TI  - Assessment of in vitro sperm characteristics after flow cytometric sorting of
      frozen-thawed bull spermatozoa.
AB  - The effect of processing prior to sex-sorting, re-freezing and thawing of frozen
      thawed bull spermatozoa on in vitro sperm characteristics was investigated.
      Frozen-thawed bull spermatozoa (three bulls; three ejaculates per bull) were
      prepared for sorting by washing (FT-WASH) or gradient centrifugation (FT
      GRADIENT) and evaluated for motility and forward progressive motility (FPM) after
      processing, staining, sorting and incubation (3 h; 37 degrees C). After frozen
      thawed samples were processed and analyzed using a high-speed cell sorter,
      aliquots were removed and re-frozen and thawed (FTF-WASH; FTF-GRADIENT). Non
      sorted frozen-thawed spermatozoa (FT-CONTROL) were also re-frozen and thawed (FTF
      CONTROL). Spermatozoa from all treatments were assessed for penetration of an
      artificial cervical mucus at 0 h after sorting or thawing, and for motility, FPM
      and acrosomal status after 3-h incubation (37 degrees C). Frozen-thawed
      spermatozoa prepared by gradient centrifugation before sorting were sorted more
      efficiently than washed samples (P < 0.05). However, after sorting (FT) or
      thawing (FTF) and incubation, the percentage of motile spermatozoa and FPM rating
      was lower for GRADIENT than WASH (21.5 +/- 3.39%; 1.4 +/- 0.16 FPM versus 48.6 +/
      4.02%, 2.6 +/- 0.16 FPM; P < 0.01). Frozen-thawed sorted spermatozoa (FT)
      penetrated in greater numbers (151.0 +/- 19.50 spermatozoa) and distance (56.3 +/
      5.11 mm) in the artificial cervical mucus and had a higher proportion of motile
      spermatozoa (65.5 +/- 2.77%) and FPM rating (2.8 +/- 0.12) after incubation than
      spermatozoa that had been re-frozen and thawed after sorting (FTF: 14.0 +/- 3.67
      spermatozoa, 21.6 +/- 3.05 mm, 12.2 +/- 1.31% and 1.2 +/- 0.10 FPM, respectively;
      P < 0.001). Regardless of processing prior to sorting, frozen-thawed sorted and
      non-sorted spermatozoa migrated similar distances in the artificial cervical
      mucus (FT-WASH: 60.0 +/- 1.2 mm; FT-GRADIENT: 57.2 +/- 0.76 mm; FT-CONTROL: 51.7
      +/- 0.69 mm). The results of this preliminary study suggested that frozen-thawed
      bull spermatozoa can be efficiently sorted into high purity X- and Y-chromosome
      enriched samples with retained functional capacity.

PMID- 15251248
TI  - Preclinical models of sexual desire: conceptual and behavioral analyses.
AB  - The epidemiology, etiology and proposed treatments for the sexual desire
      disorders are briefly reviewed before turning to an analysis of preclinical
      models. We suggest that the concept of sexual desire in the human is equivalent
      to sexual motivation as employed in the scientific literature. Many animal tests
      for sexual motivation have been described over the years. Most of them are based
      on the evaluation of the rate or speed of performing learned operant responses.
      These are not ideal measures for inferring the intensity of sexual motivation. We
      present a test for sexual incentive motivation, which has been used in male and
      female rats. No learning is involved, and the test is rather insensitive to
      variations in ambulatory activity and it does not employ rate measures. A
      procedure that recently has attracted much attention, paced-mating behavior in
      the female, does not seem to be as useful as could be expected. In fact, it does
      not appear to be superior to tests for sexual receptivity (lordosis). The lack of
      established, clinically efficient treatments for sexual desire disorders makes it
      difficult to evaluate if any model has predictive validity. However, the model
      proposed here may be isomorphic and homologous to the human condition.

PMID- 15251249
TI  - Progestins' actions in the VTA to facilitate lordosis involve dopamine-like type
      1 and 2 receptors.
AB  - In the ventral tegmental area (VTA), 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP) facilitates lordosis. Whether this involves dopamine type 1
      (D1) or dopamine type 2 (D2) receptors is of interest. Ovariectomized (ovx) rats
      with guide cannulae to the VTA were estradiol (E2) primed and pretested for
      lordosis. Rats were then infused with the D1 (Experiment 1) or D2 (Experiment 2)
      antagonists or agonists (0, 100, or 200 ng) to the VTA and were retested. After a
      second infusion of 3alpha,5alpha-THP (0, 100, or 200 ng) or vehicle, rats were
      tested 10, 60, and 120 min later. In Experiment 3, rats were administered a
      progestin receptor antagonist, RU38486, systemically or to the VTA 1 h prior to
      vehicle, SKF38393 and/or 3alpha,5alpha-THP infusions. 3alpha,5alpha-THP infusions
      increased lordosis over that seen with E2 priming. The D1 antagonist, SCH23390,
      attenuated 3alpha,5alpha-THP, but not E2-facilitated lordosis. The D1 agonist,
      SKF38393, augmented 3alpha,5alpha-THP, but not E2-facilitated lordosis. The D2
      antagonist, sulpiride, had no significant effects on lordosis. The D2 agonist,
      quinpirole, prevented 3alpha,5alpha-THP-facilitated lordosis. RU38486
      (subcutaneous) inhibited lordosis, whereas infusions to the VTA decreased
      lordosis produced by SKF38393 and 3alpha,5alpha-THP, but not 3alpha,5alpha-THP
      alone. Thus, 3alpha,5alpha-THP's actions in the VTA for lordosis may involve D1
      and/or D2 receptors.

PMID- 15251250
TI  - Sexual experience and conditioned place preference in male rats.
AB  - We have previously shown that sexual behavior induces a reward state, as
      evaluated by conditioned place preference (CPP), only when males or females are
      able to control the rate of sexual interaction. In the present experiment, we
      evaluated if male rats that are repeatedly tested in a situation in which they
      are not able to control the sexual interaction eventually develop CPP. Three
      groups of sexually naive male rats were used. One group never mated. A second
      group was tested once a week for 10 consecutive weeks in a chamber in which they
      controlled the rate of the sexual interaction. The third group was mated for the
      same number of weeks in a chamber in which the female, but not the male,
      controlled mating. The three groups were then tested for CPP. Only the group able
      to control the sexual interaction developed CPP. The group that had no control
      over the rate of the sexual interaction did not develop CPP even after 10 tests
      in which they consistently displayed sexual behavior. These results suggest that
      an estrous female and/or sexual behavior are powerful incentives that maintain
      mating even if the rewarding properties of the incentive are reduced.

PMID- 15251251
TI  - Behavioral analysis of male rat sexual motivation and performance following acute
      ethanol treatment.
AB  - To characterize the effects of acute ethanol treatment on sexual motivation and
      performance, 30 male Long-Evans rats were assigned to one of three treatment
      conditions: saline (n=9), 0.25 g/kg ethanol (n=10), or 1.0 g/kg ethanol (n=11).
      Males were injected intraperitoneally 30 min before behavioral testing. Male rats
      were placed in a multilevel testing chamber 5 min prior to the introduction of a
      receptive female rat and level changes were recorded as an index of sexual
      motivation. After the female rat was placed in the chamber, standard measures of
      sexual performance were recorded over three weekly tests. Results indicated that
      the highest dose of ethanol (1.0 g/kg) increased male rat level-changing behavior
      compared to the saline group. Although ethanol treatment failed to affect most
      measures of sexual performance, males administered 1.0 g/kg ethanol had fewer
      anogenital investigations and had longer postejaculatory intervals (PEIs)
      compared to control animals. The data from this experiment suggest that ethanol
      increases rodent sexual motivation but impairs specific parameters of sexual
      performance.

PMID- 15251252
TI  - Interaction of chronic ethanol exposure and finasteride: sex and strain
      differences.
AB  - The neurosteroid allopregnanolone (ALLOP) is a very potent positive modulator of
      gamma-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH)
      withdrawal. The 5alpha-reductase inhibitor finasteride blocks the formation of
      ALLOP from progesterone and was recently found to reduce some effects of EtOH.
      Thus, the present studies were conducted to determine the effect of finasteride
      on chronic EtOH withdrawal severity in male and female C57BL/6 (B6) and DBA/2
      (D2) mice. The animals were exposed to 72 h EtOH vapor or air and received four
      injections of finasteride (50 mg/kg ip) 24 h prior to, and each day of, the EtOH
      vapor exposure. Upon removal from the inhalation chambers, handling-induced
      convulsions (HICs) were measured hourly for the first 12 h and then again at 24
      h. EtOH withdrawal severity was significantly greater in D2 than in B6 mice.
      Pretreatment with finasteride significantly decreased EtOH withdrawal severity
      only in the female D2 mice, produced a nonselective suppressive effect on HIC in
      male B6 and D2 mice, and did not significantly alter HIC in female B6 mice.
      Finasteride pretreatment significantly decreased blood EtOH concentration (BEC)
      upon initiation of withdrawal, suggesting that finasteride may affect withdrawal
      severity via an alteration in EtOH pharmacokinetics.

PMID- 15251253
TI  - Anxiolytic effects of diazepam and ethanol in two behavioral models: comparison
      of males and females.
AB  - The present study compared the anxiolytic effects of the benzodiazepine agonist
      diazepam and ethanol in adult male and female rats. Varying doses of diazepam (1
      3 mg/kg) or ethanol (0.5-2.0 g/kg) were tested using both the elevated plus maze
      and defensive prod-burying models. Two time points following ethanol
      administration (10 and 30 min) were tested in the plus maze. Sex differences were
      seen in some anxiety-related behaviors, with females showing greater open arm
      time and reduced burying behavior than males. Although this suggests females
      displayed less anxiety-like behavior than males, the differences in the plus maze
      were not observed in all testing situations. Both diazepam and ethanol dose
      dependently increased open arm times in the plus maze and reduced burying
      behavior in the defensive prod-burying task. The parallel nature of the dose
      response curves suggests that both diazepam and ethanol have similar anxiolytic
      effects in males and females. No sex differences were seen in the brain levels of
      diazepam-like activity or blood alcohol levels with these treatments. A greater
      corticosterone response was observed in females than males with these two
      behavioral tests, but neither diazepam nor ethanol decreased this response. These
      results suggest a dissociation between the anxiety-reducing influences of these
      compounds and the changes in stress-related endocrine responses.

PMID- 15251254
TI  - Similar anxiety-like responses in male and female rats exposed to repeated
      withdrawals from ethanol.
AB  - Previous research indicated that male rats exhibited anxiety-like behavior
      following withdrawal from chronic ethanol exposure. This behavior, as well as
      other symptoms of withdrawal such as seizure susceptibility, may be sensitized in
      male rats repeatedly withdrawn from chronic ethanol exposure. Because there are
      sex differences in some alcohol effects, the present study explored whether male
      and female rats would respond differently to a course of repeated ethanol
      withdrawals. Similarly aged male and female rats were exposed to a control liquid
      diet or a diet containing ethanol (7% w/v). Ethanol-exposed rats had only one 5
      day cycle of exposure or three cycles, with 2 days of control diet (CD) between
      cycles. At 5 h after the final ethanol was removed, the rats were placed as same
      sexed pairs in the social interaction test; approximately half of the rats were
      tested later in the elevated plus maze. Rats withdrawn from ethanol after three
      cycles exhibited reduced the time spent in social interaction and general
      activity in the social interaction test and reduced the open and closed arm
      entries in the elevated plus maze. There were no sex differences in these
      effects. However, male rats exhibited a small anxiety-like response after one
      cycle of 5 days' exposure to ethanol and female rats did not. Thus, there are no
      sex differences in the three-cycle multiple-withdrawal paradigm, but there may be
      differences after briefer exposures.

PMID- 15251255
TI  - Sexually dimorphic effects of postnatal allopregnanolone on the development of
      anxiety behavior after early deprivation.
AB  - Stress early in life exerts persistent detrimental effects on brain development.
      In this experiment, a rodent model of child neglect, early deprivation (ED), was
      used to investigate the role of the neurosteroid allopregnanolone [AlloP; 3alpha
      hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP)] in the development of anxiety
      behavior. Subjects were either undisturbed controls or ED: separated individually
      for 6 h per day from postnatal day (PN) 2 to 6. Control and ED subjects were also
      either noninjected, vehicle-injected or injected with 5 mg/kg AlloP prior to the
      isolation. At PN 7, responses to 2.5 or 5 microg icv injections of AlloP were
      determined for separation-induced ultrasonic vocalizations (USVs). Tolerance to
      the USV-reducing effect of daily AlloP was seen in control but not ED pups, and
      daily AlloP reversed the expected ED suppression of USVs. As adults, controls
      treated with postnatal AlloP were less anxious than all other groups on the
      elevated plus maze. ED counteracted this effect. Male controls showed a reversal
      of the typical sex difference. There were no effects on open-field activity.
      These results suggest that the neonatal brain is responsive to alterations in
      AlloP levels, and that neuroactive progesterone metabolites may play a role in
      mediating the development of stress-related sex differences.

PMID- 15251256
TI  - Testosterone's metabolism in the hippocampus may mediate its anti-anxiety effects
      in male rats.
AB  - Androgens may mediate anxiety behaviors; however, these effects and mechanisms of
      androgens are not well understood. The following experiments investigated whether
      testosterone (T)'s effects on anxiety behavior are mediated by its 5alpha
      reduced, nonaromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha
      hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha
      androstanediol (3alpha-diol). In Experiment 1, gonadally-intact adult male rats
      and gonadectomized (GDX), DHT-replaced rats had similar low levels of anxiety
      behavior in the open field and elevated plus maze and fear behavior in the
      defensive freezing task compared with GDX control rats. In Experiment 2, intact
      or DHT-replaced rats that received blank inserts to the hippocampus demonstrated
      less anxiety behavior than did rats administered an implant of indomethacin, a
      3alpha-HSD inhibitor, to the dorsal hippocampus. These data indicate that T's
      5alpha-reduced metabolite, DHT, can reduce anxiety behavior and that blocking
      metabolism to 3alpha-diol in the hippocampus can attenuate these effects.

PMID- 15251257
TI  - Androgens in the hippocampus can alter, and be altered by, ictal activity.
AB  - Steroid hormones, such as androgens, can modulate seizure processes. This review
      summarizes prior research and presents new data that support the role of
      androgens in modulating seizure processes. Testosterone, the primary endogenous
      androgen, has antiseizure effects in people and in animal models of epilepsy.
      Furthermore, testosterone's antiseizure effects may involve actions of its 5alpha
      reduced metabolite and neuroactive steroid, 5alpha-androstane-3alpha,17beta-diol
      (3alpha-diol). The hippocampus is a target for androgen action and is involved in
      many types of seizure disorder. Data suggest that actions of androgens in the
      hippocampus may be important for androgens' antiseizure effects. Interestingly,
      there may also be a reciprocal relationship between androgens and seizures. Ictal
      activity can alter the gonadal responsiveness of people with epilepsy and in
      animal models of seizure disorder. Thus, this paper will review data in support
      of androgens' antiseizure effects. Further understanding of androgens' role in
      seizure processes is important for potential therapeutic effects.

PMID- 15251258
TI  - Sex differences in effects of mild chronic stress on seizure risk and GABAA
      receptors in rats.
AB  - Social stress is a common occurrence in our society that can negatively impact
      health. Therefore, we wanted to study the effects of a mild stressor designed to
      model social stress on seizure susceptibility and GABAA receptors in male and
      female rats. The mild chronic stress of individual housing consistently decreased
      bicuculline (but not pentylenetetrazol, PTZ) seizure thresholds by 10-15% in both
      sexes. Housing conditions did not alter the anticonvulsant activity of diazepam
      or ethanol, although the anticonvulsant effect of ethanol was significantly
      greater against PTZ-induced seizures. Experiments testing the addition of an
      acute restraint stress unmasked sex differences in seizure induction. The acute
      stress also selectively decreased the potency of GABA to modulate GABAA receptor
      mediated chloride uptake in group-housed females. There were additional sex
      differences by housing condition for GABAA receptor-gated chloride uptake but no
      differences in [3H]flunitrazepam binding. We also found significant effects of
      sex and housing on ethanol-induced increases in corticosterone (CORT) levels. In
      summary, there were complex and sex-selective effects of mild chronic stress on
      seizure induction and GABAA receptors. Gaining a better understanding of
      mechanisms underlying interactions between sex and stress has important
      implications for addressing health concerns about stress in men and women.

PMID- 15251259
TI  - 3alpha,5alpha-THP mediates progestins' effects to protect against adrenalectomy
      induced cell death in the dentate gyrus of female and male rats.
AB  - Progestins have neuroprotective effects in several in vitro models of
      neurodegeneration and in vivo in seizure models. The extent to which
      progesterone's in vivo protective effects may generalize to models not involving
      seizure processes and whether progesterone's protective effects are modulated by
      its metabolites have not been comprehensively investigated. The present
      experiments investigated the effects of progesterone and its metabolites,
      dihydryoprogesterone (DHP) and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha
      THP), to protect the hippocampus from damage induced by adrenalectomy (ADX). In
      Experiments 1 and 2, progesterone, DHP, or 3alpha,5alpha-THP administration (1
      mg/kg sc) to female (Experiment 1) or male (Experiment 2) rats similarly reduced
      the total number of ADX-induced pyknotic cells in the dentate gyrus compared with
      vehicle administration. In Experiment 3, blocking progesterone's metabolism to
      3alpha,5alpha-THP with coadministration of a 5alpha-reductase inhibitor,
      finasteride (10 mg/kg sc), in female rats attenuated progesterone's protective
      effects on cell death in the dentate gyrus. Together, these data suggest that
      progestins can protect against ADX-induced cell death and that the actions of the
      progesterone metabolite, 3alpha,5alpha-THP, may underlie these effects.

PMID- 15251260
TI  - Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of
      Parkinson's disease.
AB  - The incidence of certain neurological disorders, including Parkinson's disease,
      appears to be more prevalent in men. Studies involving estrogen treatment of
      ovariectomised rodents attribute this largely to the neuroprotective effects of
      estrogen. However, a neuroprotective role for physiological levels of circulating
      hormones in males and females is less clear. Using the 6-hydroxydopamine (6-OHDA)
      model of Parkinson's disease to lesion the nigrostriatal dopaminergic (NSDA)
      pathway, we have shown that in females, endogenously produced estrogen is
      neuroprotective, whereas in males, gonadal factors increase striatal 6-OHDA
      toxicity. Intriguingly, estrogen, but not dihydrotestosterone, a nonaromatizable
      androgen, reversed the effects of orchidectomy on lesion size, raising the novel
      the hypothesis that enhanced male susceptibility may be attributable to the
      effects of endogenous testosterone only after its aromatization to estrogen.
      Thus, estrogen appears to exert opposite effects in the NSDA in males and
      females, being neuroprotective in females, but not in males, where it may even
      exacerbate neurodegenerative responses, with important implications for the
      clinical potential of estrogen-related compounds as neuroprotective agents.
      Preliminary experiments support the hypothesis that sex differences in the adult
      NSDA may result from the organisational actions of gonadal steroids during the
      critical neonatal period for the masculinization of the brain. Further studies
      are needed to determine whether this early organisation of a sexually
      differentiated neural circuitry may contribute to the emergence of
      neurodegenerative conditions such as Parkinson's disease.

PMID- 15251261
TI  - Antidepressant effects of ERbeta-selective estrogen receptor modulators in the
      forced swim test.
AB  - Estradiol (E2) may influence depressive symptomology of women and decrease
      depressive behavior among rodents. The mechanism(s) for E2's antidepressant
      effects are not well understood. To determine whether antidepressant effects of
      E2 may involve actions at intracellular estrogen receptor (ER) alpha or beta
      isoforms, selective ER modulators (SERMs) were administered (10 microg sc) to
      ovariectomized rats 48 h before testing in the forced swim test, an animal model
      of depression, and the horizontal crossing task. Rats received sesame oil
      vehicle, 17beta-E2, which has a high affinity for ERalpha and ERbeta, SERMs that
      vary in their activity at ERalpha and beta, or a tricyclic antidepressant
      (desipramine; 30 mg/kg ip), as a positive control. ERalpha-selective SERMs were
      propyl pyrazole triol (PPT) and 17alpha-E2. PPT has more selective effects at
      ERalpha than does 17alpha-E2, which also binds ERbeta. ERbeta-selective SERMs
      were diarylpropionitrile (DPN) and 7,12-dihydrocoumestan (coumestrol). DPN is
      more selective at ERbeta than coumestrol, which also binds ERalpha. 17beta-E2,
      ERbeta-selective SERMs (DPN, coumestrol), and desipramine administration produced
      antidepressive behavior (decreased immobility, increased struggling and
      swimming). ERalpha-selective SERMs (PPT, 17alpha-E2) were not different from
      vehicle. There were no differences among groups in the number of beam breaks made
      in the horizontal crossing task. These data suggest that E2's antidepressive
      effects may involve actions at ERbeta.

PMID- 15251262
TI  - Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and
      lactating rats.
AB  - The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20
      one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive
      behavior of female rats in part through actions in the hippocampus. To
      investigate, forced swim test behavior and plasma and hippocampal progestin
      levels were assessed in groups of rats expected to differ in their 3alpha,5alpha
      THP levels due to endogenous differences (pregnant and postpartum),
      administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or
      gestational stress [prenatal stress (PNS)], an animal model of depression.
      Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less
      depressive behavior (decreased immobility, increased struggling and swimming) in
      the forced swim test than did postpartum rats. Finasteride, compared to vehicle
      administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and
      increased depressive behavior (increased immobility, decreased struggling and
      swimming). PNS was associated with lower hippocampal, but not plasma,
      3alpha,5alpha-THP levels and increased swimming compared to that observed in
      control rats. Together, these data suggest that 3alpha,5alpha-THP in the
      hippocampus may mediate antidepressive behavior of female rats.

PMID- 15251263
TI  - Chronic stress alters amphetamine effects on behavior and synaptophysin levels in
      female rats.
AB  - Previous studies show that stress cross-sensitizes with or alters amphetamine
      (AMPH) effects in male rats; however, few studies include females. We
      investigated combining daily restraint stress (21 days for 6 h/day) with chronic
      AMPH (10 injections every other day) on locomotor activity, exploratory activity
      in an open field and object recognition, a memory task, in female rats. A
      synaptic protein, synaptophysin, was also quantified by radioimmunocytochemistry
      (RICC) in brain to determine possible mechanisms for behavioral changes.
      Beginning at 5 days after cessation of treatments, AMPH increased locomotion,
      modified exploration, impaired object recognition, and increased serum
      corticosterone (CORT) levels. Stress did not alter these parameters but blocked
      AMPH effects on exploration and object recognition, potentiated AMPH-dependent
      locomotor effects, and did not alter increased CORT levels. AMPH treatment
      decreased synatophysin expression in the hippocampus. In the caudate nucleus, the
      AMPH group showed increased synaptophysin expression which was reversed by
      stress. These results in females corroborate previously shown cross
      sensitizations between stress and AMPH for locomotion in males and demonstrate
      that chronic stress counteracts AMPH-dependent impairments in recognition memory.
      Stress may counteract AMPH effects on the memory task by blocking both the
      induction of AMPH anxiety-like effects and neuroplastic changes in the caudate
      nucleus of female rats.

PMID- 15251264
TI  - Estrogen has mnemonic-enhancing effects in the inhibitory avoidance task.
AB  - Gonadal hormones, such as estrogen, can alter cognitive performance. The present
      studies investigated the relationship between performance on the inhibitory
      avoidance task and endogenous fluctuations in ovarian hormones and estrogen
      replacement. In Experiment 1, proestrous or diestrous I female, or male, rats
      were trained in the inhibitory avoidance task. Following a 24-h intertrial delay,
      when female rats were tested in metestrus or diestrus II, no differences in
      crossover latencies were observed among groups. In Experiment 2, female rats in
      proestrus or diestrus I, and male rats, were trained in the inhibitory avoidance
      task and were tested following a 4-h intertrial delay (so that training and
      testing were accomplished in the same phase of the cycle). In this paradigm,
      proestrous rats had significantly longer crossover latencies than did either
      diestrous I or male rats. Posttraining administration of estrogen, but not
      progesterone, to ovariectomized rats increased crossover latencies compared to
      vehicle with a 4-h (Experiment 3) or 24-h (Experiment 4) intertrial delay. In
      Experiment 5, estrogen administration to ovariectomized rats immediately, but not
      1, 2, or 3 h posttraining, increased crossover latencies compared to vehicle.
      Together, these data suggest that estrogen can have positive mnemonic effects in
      the inhibitory avoidance task.

PMID- 15251265
TI  - Mnemonic effects of testosterone and its 5alpha-reduced metabolites in the
      conditioned fear and inhibitory avoidance tasks.
AB  - Experiments were conducted to examine whether performance in hippocampally
      mediated learning tasks is influenced by testosterone (T) and/or its 5alpha
      reduced metabolites, dihydrotestosterone (DHT) and 3alpha-androstanediol (3alpha
      diol). Performance in the conditioned fear and inhibitory avoidance tasks were
      examined in intact and gonadectomized (GDX), androgen-replaced rats. In
      Experiment 1, the behavior of intact and GDX rats in the conditioned fear
      paradigm were compared. GDX rats spent more time freezing, an index of increased
      learning, in the context, hippocampally-mediated task, but not in the cued,
      amygdala-mediated task. In Experiment 2, GDX rats were administered T, DHT,
      3alpha-diol, estrogen (E2), or vehicle 1 mg/kg sc after training in the
      conditioned fear paradigm. T-, 3alpha-diol-, or E2-, compared with vehicle
      administered rats, spent significantly more time freezing in the contextual, but
      not the cued, condition. In Experiment 3, intact compared with GDX rats had
      significantly longer crossover latencies, indicating better performance, in the
      inhibitory avoidance task. In Experiment 4, T, DHT, 3alpha-diol, or vehicle 1
      mg/kg sc was administered to GDX rats immediately following training in the
      inhibitory avoidance task. Rats administered T, DHT, or 3alpha-diol had
      significantly longer crossover latencies compared with vehicle controls. In
      Experiment 5, androgen levels in the hippocampus were elevated 1 h following
      administration, when androgen exposure is essential for consolidation. These data
      indicate that androgens effects to enhance learning may be mediated in part by
      actions of 5alpha-reduced metabolites in the hippocampus.

PMID- 15251266
TI  - Acute stress impairs spatial memory in male but not female rats: influence of
      estrous cycle.
AB  - We investigated how sex and estrous cycle influenced spatial recognition memory
      in the Y-maze after exposure to acute restraint stress. In Experiment 1, intact
      male and female rats were restrained for 1 h and then 2 h after the start of
      restraint, rats were trained on the Y-maze. After a 4 h delay, hippocampal
      dependent spatial recognition memory was assessed. Acute stress produced opposite
      patterns between the sexes with spatial memory being impaired in males and
      facilitated in females. Serum corticosterone measures indicated that both sexes
      showed a robust corticosterone response after restraint and a moderate
      corticosterone response after Y-maze exposure. Serum corticosterone levels in
      response to restraint and Y-maze were not statistically different between the
      sexes. Experiment 2 examined the influence of the estrous cycle on spatial memory
      ability after acute stress. Acute stress facilitated spatial memory in females
      compared to controls, regardless of the estrous cycle phase (estrus and
      proestrus). Moreover, females in proestrus showed higher serum corticosterone
      levels during restraint compared to females in estrus. No differences in
      corticosterone levels were observed at baseline or following 2 h of recovery from
      restraint. These data show important differences in how sex and estrous cycle
      influence cognitive functions following acute stress.

PMID- 15251268
TI  - Functional responses to the cannabinoid agonist WIN 55,212-2 in neonatal rats of
      both genders: influence of weaning.
AB  - We have studied behavioural, biochemical and endocrine responses to the
      cannabinoid agonist WIN 55,212-2 (WIN) in neonatal rats, as well as the effects
      of weaning on such responses. We used preweanling rats (20 days of age), 25-day
      old weaned rats (weaning at Day 22) and 25-day-old nonweaned rats of both sexes.
      The behavioural effects of WIN were assessed in the nociceptive tail immersion
      test and in the open field. We also analysed the effect of weaning on
      corticosterone responses to WIN (radioimmunoassay) as well as on WIN-stimulated
      [35S] GTPgammaS binding in periaqueductal grey (PAG) and striatum. The
      cannabinoid agonist induced a modest increase in pain thresholds, whereas the
      effect of the drug on open-field activity, particularly on vertical activity, was
      much more marked. The weaning process appeared to reduce the baseline nociceptive
      latencies of the female rats. No significant effect of weaning on the behavioural
      responses to WIN was found. However, the group of weaned females (but not males)
      showed a significantly reduced WIN-stimulated [35S] GTPgammaS binding in the
      striatum. The cannabinoid agonist significantly increased the corticosterone
      levels of 25-day-old rats with the effect being more marked in weaned than in
      nonweaned animals. The results suggest that the weaning process might produce
      some sexually dimorphic developmental changes in CB1 receptor function.

PMID- 15251267
TI  - Sex differences and repeated intravenous nicotine: behavioral sensitization and
      dopamine receptors.
AB  - The present study examined the sex-dependent expression of behavioral
      sensitization as well as changes of dopamine (DA) transporters and D1, D2, and D3
      receptors following repeated intravenous nicotine administration. Male and female
      Sprague-Dawley rats were implanted with indwelling jugular catheters, equipped
      with subcutaneous intravenous injection ports. Rats were habituated to activity
      chambers for 3 days and were subsequently administered 15-s bolus injections of
      intravenous nicotine (50 microg/kg/ml) 1/day for 21 days. Animals were placed in
      activity chambers for 60 min immediately after the 1st and 21st nicotine
      injection. Observational time sampling was also performed. Brains were
      subsequently removed and frozen for autoradiographic DA transporter/DA receptor
      analysis on the afternoon females were in proestrus. With one exception, no
      robust sex differences were observed for locomotor activity or any rearing
      measures either during baseline or after initial nicotine injection. Females
      exhibited markedly more behavioral sensitization of locomotor activity, rearing,
      duration of rearing, and incidence of observed rearing. There were no sex
      differences in the number of D1 or D2 receptors. Females exhibited an increased
      number of DA transporters and decreased D3 receptors in the NAcc, relative to
      males. Multiple regression analyses suggest that D3 receptors and DA transporters
      in various striatal and NAcc subregions differentially predicted nicotine-induced
      behaviors for males and females. Collectively, these findings demonstrate that
      repeated intravenous nicotine produces sex differences in the expression of
      behavioral sensitization, and suggest that nicotine-induced changes of DA
      transporters and D3 receptors are partly responsible for increased behavioral
      sensitization in female rats.

PMID- 15251269
TI  - No difference in responsiveness to a low dose of alcohol between healthy women
      and men.
AB  - The purpose of the current study was to examine gender-related differences in
      alcohol responsiveness by comparing the effect of a low-dose intravenous alcohol
      infusion upon saccadic eye movements, self-rated sedation and intoxication
      scores. The functional sensitivity to a low dose of alcohol in 12 healthy women
      and 12 healthy men was evaluated by comparing the effects of an intravenous
      alcohol infusion on a number of saccadic eye movement measures, including
      saccadic eye velocity (SEV), saccade latency, saccade accuracy, saccade
      deceleration and self-rated levels of intoxication and sedation. The infusion of
      a low dose of alcohol induced a decrease in SEV and increased saccade
      deceleration and self-rated scores of intoxication in both males and females.
      Saccade accuracy was also significantly deteriorated by alcohol in both groups.
      The alcohol infusion did not induce any main gender-related differences in the
      saccade or visual analogue scale measurements. According to the findings of the
      present study, no gender differences in the responsiveness to a low-dose alcohol
      infusion were found.

PMID- 15251270
TI  - Binge drinking and sex: effects on mood and cognitive function in healthy young
      volunteers.
AB  - This study compared the mood and cognitive performance of male and female
      teetotal and binge drinking students. The binge drinkers had significantly lower
      self-ratings of trait anxiety and depression and of state alertness at the time
      of testing than did the teetotallers. The females had significantly higher
      ratings of trait and state anxiety, but there were no Sex x Bingeing interactions
      on mood. The binge drinkers made significantly fewer correct responses in a test
      of sustained attention and recalled fewer line drawings. There was a significant
      Sex x Binge interaction in a spatial recognition task because the male, but not
      the female, binge drinkers were slower to make correct responses. Males performed
      better than females in both the spatial and pattern recognition memory tasks.
      There were three tests of executive function. In a spatial working memory task,
      males performed better than females, but there were no effects of binge drinking.
      There were no effects in a test of mental flexibility. However, in a test of
      planning, the binge drinkers were significantly slower than the teetotallers
      were. Thus, compared with a group of teetotallers, the binge drinkers had lower
      trait anxiety and depression and poorer performance in tests of sustained
      attention, episodic memory and planning ability.

PMID- 15251271
TI  - Mood changes after cognitive testing in late middle-age: impacts of sex and
      habitual alcohol consumption.
AB  - Men and women (50-67 years) completed drinking diaries and, on the basis of this,
      were divided into low (<2 units/day, 1 UK unit=8 g alcohol) and moderate (2-5
      units/day) alcohol groups. They completed analogue rating scales of mood and
      bodily symptoms before and after two extended computerised cognitive tests. After
      the tests, the women showed significantly greater increases in self-ratings on
      the factors of anxiety and discontentment and felt significantly less alert than
      did the men. They also showed significantly greater increases in bodily symptoms
      of somatic anxiety and ratings of aggressive mood than did the men. There were no
      significant effects of alcohol or Sex x Alcohol interactions on the self-ratings,
      but the men showed significant positive correlations of alcohol and negative
      mood. On both the cognitive tests, there were significant Sex x Alcohol
      interactions because the moderate-drinking men performed worse than the low
      drinking men, whereas the moderate-drinking women performed better than the low
      drinking women. Thus, the middle-aged women responded much more than did the men
      with negative mood changes to the psychological stress of cognitive testing,
      although their cognitive performance was not worse.

PMID- 15251272
TI  - Does drinking have effects on mood and cognition in male and female students?
AB  - Self-ratings of mood and bodily symptoms were made by groups of IQ and education
      matched male and female students [teetotal, low (2-9 units/week for both sexes; 1
      UK unit=8 g alcohol) and moderate (12-34 units/week for males; 10-24 units/week
      for females) drinkers], before the start and at the end of cognitive testing.
      Multivariate analyses of variance (MANOVAs) showed that there were significant
      Alcohol x Time interactions, because the teetotal group responded to the
      cognitive tests with greater increases in the factors of somatic anxiety and
      aggressive mood than did the other two groups. Thus, the teetotallers had greater
      ratings of anxiety, sweating, palpitations, irritability, headache, feeling
      angry, quarrelsome, belligerent, resentful, hostile, spiteful and rebellious. No
      differences were found in immediate or delayed logical memory, in verbal fluency,
      trails, clock-drawing or mental flexibility tests. In tests of sustained
      attention [rapid visual information processing (RVIP)] and planning, males
      performed better than females. The moderate-alcohol group performed better than
      the low-alcohol group in RVIP and planning (completed significantly more tasks in
      the minimum moves), although in the hardest parts of the latter test, they took
      longer in planning the initial move. In conclusion, there was no evidence that
      the group drinking moderate levels of alcohol had any cognitive impairment and
      the teetotal group responded to the cognitive tests with the greatest increases
      in negative mood.

PMID- 15251273
TI  - Effects of transdermally administered nicotine on aspects of attention, task
      load, and mood in women and men.
AB  - This double-blind placebo-controlled study was conducted to determine nicotine
      effects on diverse types of attentional performance, task load, and mood
      considering sex effects as suggested by animal studies. Twelve smokers, 12
      deprived smokers and 12 nonsmokers (6 females, 6 males in each group) were
      investigated. Participants were treated either by 5 mg/16 h nicotine patches
      (Nicorette) or placebo. Effects of treatment were examined by a computerized
      attention-test battery; mood was assessed by the Berliner-Alltagssprachliches
      Stimmungs-Inventar and task load by the NASA Task Load Index (NASA-TLX). Results
      showed that nicotine significantly increased the number of hits and decreased
      reaction time (RT) in the vigilance task. In the selective attention task
      combined with irrelevant speech as background noise, nicotine enhanced rate of
      hits. Although it was indicated that nicotine leads to a generally higher
      accuracy in attention tasks, response time of visual search was prolonged,
      contradicting a universal facilitation by nicotine. Participants experienced
      mental demand and temporal demand lower and rated alertness higher when in the
      nicotine condition. These effects were independent of smoking status, indicating
      "true" nicotine effects. Females took significant advantage of nicotine in the
      vigilance task, reaching the performance level of males, accompanied by a higher
      rated alertness. Results indicate task- and sex-dependent nicotine effects.

PMID- 15251274
TI  - Cue reactivity in smokers: the effects of perceived cigarette availability and
      gender.
AB  - We examined the effects of perceived cigarette availability and gender on smoking
      cue reactivity. Smokers were exposed to smoking cues (smoking paraphernalia) and
      control cues whilst their subjective and physiological responses were measured.
      Perceived cigarette availability was manipulated on a between-subjects basis
      before cue exposure. Relative to control cues, smoking cues evoked increases in
      the level of skin conductance in all participants. Cigarette craving was also
      increased in the presence of smoking cues, but only in female participants.
      Perceived cigarette availability had no effect on these responses. Participants
      also showed salivary reactivity to smoking cues, with males showing a decrease in
      salivation, and females showing an increase, but only when cigarettes were
      perceived as unavailable. These results suggest that perceived cigarette
      availability may not influence craving and skin conductance reactivity to smoking
      cues in minimally dependent smokers who are not nicotine deprived. In addition,
      the present data suggest that there are important gender differences in craving
      reactivity to smoking cues.

PMID- 15251275
TI  - Metarhizium spp., cosmopolitan insect-pathogenic fungi: mycological aspects.

PMID- 15251276
TI  - Molecular biology of the Burkholderia cepacia complex.

PMID- 15251277
TI  - Non-culturable bacteria in complex commensal populations.

PMID- 15251278
TI  - Lambda red-mediated genetic manipulation of antibiotic-producing Streptomyces.

PMID- 15251279
TI  - Colicins and microcins: the next generation antimicrobials.

PMID- 15251280
TI  - Mannose-binding quinone glycoside, MBQ: potential utility and action mechanism.

PMID- 15251281
TI  - Protozoan grazing of freshwater biofilms.

PMID- 15251282
TI  - Metals in yeast fermentation processes.

PMID- 15251283
TI  - Interactions between Lactobacilli and antibiotic-associated diarrhea.

PMID- 15251284
TI  - Bacterial diversity in the human gut.

PMID- 15251285
TI  - Interpreting the host-pathogen dialogue through microarrays.

PMID- 15251286
TI  - The inactivation of microbes by sunlight: solar disinfection as a water treatment
      process.

PMID- 15251287
TI  - Low molecular weight dicarboxylic acids in PM10 in a city with intensive solid
      fuel burning.
AB  - In this work, PM(10) samples were collected in a winter and a summer in
      Christchurch, a New Zealand city having intensive wood and coal burning and a
      serious air pollution problem in winter. Oxalic, malonic, succinic, maleic,
      glutaric and adipic acids in the samples were analysed using ion chromatography.
      It was suggested that solid fuel burning had large influence on the occurrence of
      these low molecular weight dicarboxylic acids resulting in significantly higher
      wintertime concentrations of maleic acid, oxalic acid and glutaric or adipic
      acid. The most pronounced feature observed was that maleic acid was the second
      most abundant species of the detected DCAs in the winter (with a mean of 74 ngm(
      3) and the highest concentration ever reported of 231 ngm(-3)). In contrast,
      malonic acid experienced a low abundance in both seasons. The observed seasonal
      patterns and molecular distribution were inconsistent with those in most other
      urban areas. On an average, the total detected dicarboxylic acids accounted for
      about 0.5% of PM(10) mass with a maximum of 1.4% in the winter. The relative
      importance of different sources to individual dicarboxylic acids varied with
      seasons and is discussed in detail.

PMID- 15251288
TI  - Synthesis of polychlorinated biphenyls and their metabolites with a modified
      Suzuki-coupling.
AB  - A modified procedure for the synthesis of polychlorinated biphenyls (PCBs)
      utilizing the Suzuki-coupling, a palladium-catalyzed cross-coupling reaction, is
      described. The coupling of (chlorinated) benzene boronic acids with
      bromochlorobenzenes, using Pd(dppf)(2)Cl(2) (dppf = 1,1'
      bis(diphenylphosphino)ferrocene) as the catalyst and aqueous sodium carbonate as
      the base, gave the desired PCB congeners in moderate to good yields. Eleven PCB
      congeners, including environmentally important PCB congeners and metabolites,
      were synthesized using this modified procedure. This new catalyst
      Pd(dppf)(2)Cl(2) offers the advantage of being less air-sensitive and has a
      longer shelf life compared to Pd(PPh(4))(4). Three new (di-)methoxylated PCB
      congeners were synthesized using the same procedure by either coupling a
      chlorinated benzene boronic acid with a bromo (di-)methoxybenzene or by coupling
      a (di-)methoxy benzene boronic acid with a chlorinated bromobenzene. The
      dimethoxylated PCB congeners were readily converted into the respective
      dihydroxylated PCB derivatives using boron tribromide in dichloromethane. This
      approach offers the advantage of high selectivity and moderate to good yields
      compared to conventional methods such as the Cadogan reaction and allows the use
      of less toxic starting materials.

PMID- 15251289
TI  - Elaboration of new formulations to remove micropollutants in MSWI flue gas.
AB  - This study consists in identifying and testing potential inorganic substitutes to
      carbon based materials commonly used as adsorbents for the removal of organic
      pollutants such as dioxins and furans released from Municipal Solid Waste
      Incinerators (MSWI). Although carbon materials enable to reach the current
      regulation in terms of dioxins and furans emissions, they exhibit a potential
      auto ignition risk when present in hot flue gases. Here, the adsorption potential
      of carbon based products is compared to the one of some inorganic materials.
      Chlorobenzene was chosen as a reference molecule to compare the removal
      performance of the different adsorbents. This comparison was based on the
      determination of the adsorption energies derived from temperature programmed
      desorption (TPD) experiments. In the first part of this study, five inorganic
      materials were selected according to their chlorobenzene adsorption performance
      compared to those of carbon based products currently used to remove
      micropollutants from MSWI flue gases. In the second part of the study, the
      influence of the inlet concentration of adsorbate on the adsorption potential of
      sorbents is investigated. Actually, the organic compound concentration was
      decreased in order to be closer to those met in MSWI. Furthermore, the adsorption
      experiments were performed with other adsorbates whose molecular mass or chlorine
      content are higher. Thanks to these adsorption results a new organic free
      formulation has been proposed for the removal of micropollutants. Tests carried
      out on an industrial scale, demonstrated that this product enables to reach the
      current norm concerning dioxins and furans emissions.

PMID- 15251290
TI  - Distribution of organochlorine pesticides, polychlorinated biphenyls and alpha
      HCH enantiomers in pork tissues.
AB  - The distribution of HCH isomers, DDT analogues and selected PCB congeners in pork
      organs collected from the same individuals raised in Romanian farms was
      investigated. Organochlorine pesticides (HCHs and DDTs) were the principal
      contaminants in all samples, while PCB concentrations were low, in accordance
      with previously reported concentrations from Romanian animal farms. The most part
      of the pollutant load in the body is retained in the adipose tissue, with HCHs
      ranging between 16 and 27.7 ng/g lipid and with higher concentrations of DDTs
      ranging between 65.9 and 334.5 ng/g lipid. The highest PCB levels (up to 32 ng/g
      lipid) were measured in lung and liver. The lipid-normalized concentrations in
      the brain were lower than in all other tissues due to the presence of the blood
      brain barrier or due to a lower proportion of the neutral lipids such as
      triglycerides. The highest concentrations of DDTs were measured in muscle and
      fat, with p,p'-DDE being the principal contributor and with a variable
      contribution of p,p'-DDD and p,p'-DDT. In liver, p,p'-DDD has a higher
      contribution to the sum DDTs, while in all analyzed livers, the concentration of
      p,p'-DDT was very low. beta-HCH was the most persistent HCH isomer in all
      tissues, accounting for 40-97% of sum HCHs. For all animals, the highest
      concentrations of beta-HCH and HCHs were found in liver, while the lowest HCH
      concentrations were measured in brain and spinal marrow. Additionally, the
      distribution of alpha-HCH enantiomers in the tissues was discussed. In all
      samples (except 2 brain samples), (+) alpha-HCH was depleted and (-) alpha-HCH
      was enantioenriched. Enantiomeric ratios in brain were the highest measured
      values between all organs. For all studied animals, ERs increased in the order
      fat < muscle < liver < brain.

PMID- 15251291
TI  - Polybrominated methoxy diphenyl ethers (MeO-PBDEs) in fish and guillemot of
      Baltic, Atlantic and Arctic environments.
AB  - Arctic cod liver samples from Vestertana Fjord at the Arctic coast of Norway,
      salmon and guillemot samples from the Baltic Sea and the Atlantic Ocean, and
      salmon and lamprey larva samples from Kymijoki River in southern Finland were
      analysed for the occurrence of tri-, tetra- and pentabromomethoxy diphenyl ethers
      and their concentration levels were estimated. These compounds have previously
      been identified by other research groups in salmon, seal and dolphin samples. The
      aim of this study was to find out a possible temporal trend in the concentrations
      of these compounds in the cod liver samples from years 1987-1998 and to
      investigate the possible spatial differences in the concentrations in biota
      samples from the Baltic Sea, Atlantic Ocean, Arctic Sea and contaminated
      freshwater river. Two most abundant methoxy-tetrabromo diphenyl ether congeners
      occurred in the same statistically significant ratio in 14 sea biota samples.
      Levels in lamprey larvae were below detection limit. The origin of these
      methoxylated bromodiphenyl ethers in biota samples remained unknown. They may be
      metabolites of polybrominated diphenyl ethers used as flame retardants or
      compounds of natural origin.

PMID- 15251292
TI  - Pesticide and plasticizer residues in bergamot essential oils from Calabria
      (Italy).
AB  - Organophosphorus and organochlorine pesticides, phosphorated plasticizers,
      chloroparaffins and phthalate esters contamination in bergamot essential oils
      produced in Calabria in the crop years 1999-2000 was studied by HRGC in
      connection with detectors FPD, ECD, MS. Residues of dicofol and tetradifon were
      found in oils from both crop years. The mean dicofol concentration was 0.26 mg/l
      in samples from 1999 and 0.20 mg/l in those from 2000; the mean tetradifon
      content was 0.06 mg/l for both the crop years. Among plasticizers, residues of
      diisobutyl phthalate, di-n-butyl phthalate, and bis(2-ethylhexyl) phthalate were
      found in samples from crop years 1999 and 2000, the mean content were 1.22 and
      1.23 mg/l, 1.51 and 1.65 mg/l, 1.38 and 1.42 mg/l respectively.

PMID- 15251293
TI  - Distribution characteristics of nonylphenols in the artificial Lake Shihwa, and
      surrounding creeks in Korea.
AB  - Nonylphenols were determined from the water, suspended particle, and sediment
      samples taken from the Lake Shihwa in Korea and its surrounding creeks flowing
      through municipal and industrial areas, and into the lake. The nonylphenols were
      detected at the concentration ranges of 0.0-41.3 microg/l, 0.0-116.6 and 0.3-31.7
      mg/kg in water, suspended particle and sediment samples respectively. The
      contamination levels of nonylphenols were increased along the down stream.
      Considerably high levels of nonylphenols were found at the industrial area
      compared to the municipal area. No remarkable differences were found between the
      isomer patterns of nonylphenols for the sample matrices of each sampling site,
      i.e. water, suspended solids and sediment. Strong correlations between water and
      sediment with 10(5.2) of the mean partition coefficient (Koc ) were observed.
      These indicate that most of nonylphenols came from industrial wastewater at high
      level. It is thought that the water quality of the Lake Shihwa is affected
      greatly by industrial environments surrounding.

PMID- 15251294
TI  - Theoretical models to evaluate hazard due to organochlorine compounds (OCs) in
      Mediterranean striped dolphin (Stenella coeruleoalba).
AB  - Many studies document the chemical stress related to organochlorine (OC)
      xenobiotics in Mediterranean cetaceans. The aim of this study was to establish a
      theoretical model to evaluate the hazard to Mediterranean striped dolphins
      (Stenella coeruleoalba) due to HCB, DDTs and PCB congeners. Differences in OC
      levels in blubber of stranded and free-ranging specimens enabled us to evaluate
      the hazard associated with different chlorinated xenobiotics, taking the live
      population as control sample, assumed to be in good health. For the most toxic
      compounds, with teratogenic, mutagenic, carcinogenic and endocrine disrupting
      capacity, we indicate levels beyond which there can be toxicological hazard for
      the striped dolphin. Using a mathematical formula derived from knowledge of the
      length and age of 62 stranded specimens, the age of dolphins was estimated and
      sexual maturity was identified at nine years. This evaluation was important for
      understanding differences in contaminant burden between males and females.

PMID- 15251295
TI  - Bioremediation of HCH-contaminated soil: elimination of inhibitory effects of the
      insecticide on radish and green gram seed germination.
AB  - The effects of technical grade hexachlorocyclohexane (tech-HCH) on the
      germination of different seeds were tested. Two types of seeds, radish and green
      gram showed marked reduction in germination percentage and seeding vigour index.
      The abnormalities and reduction in germination increased with increasing
      concentration of tech-HCH. At 100 microg HCH level the germination of radish and
      green gram seeds was inhibited almost completely on moist filter paper and soil.
      Protease and amylase activities were reduced in seeds grown in soil spiked with
      tech-HCH. Bioremediation of HCH-spiked soils with a HCH-degrading microbial
      consortium helped in eliminating the toxic effects of tech-HCH towards seed
      germination. The degradation of 25 microg tech-HCH g(-1) soil was complete by 120
      h. The seed germination and the activities of the assayed enzymes, amylase and
      protease, were same as before or better in bioremediated soils.

PMID- 15251296
TI  - Altered menstrual cycles in women with a high dietary intake of persistent
      organochlorine compounds.
AB  - Dietary exposure to persistent organochlorine compounds (POCs) has been found to
      affect the menstrual cycle in both animals and humans. In Sweden, the major
      exposure route for POCs is the consumption of fatty fish from the Baltic Sea.
      Thus, women who eat relatively large amounts of this fish constitute a suitable
      study group when investigating a possible association between dietary exposure to
      POC and menstrual cycle disruption. Questionnaires were sent to the exposed
      women, as well as to a socioeconomically similar cohort of controls, and
      information was collected on their menstrual cycles. Since the exposed women
      tended to smoke more than the controls, all results were adjusted for smoking
      habits. A cohort comparison found that the exposed women on average had 0.46 (95%
      confidence interval: 0.03, 0.89) days shorter menstrual cycles than controls.
      However, within the exposed cohort no effects were found of the proxy variables
      early life exposure and high consumption of Baltic Sea fatty fish. The results
      give some support to previous results from studies on women with similar
      exposure, but are not conclusive with respect to whether there is a causal
      association between POC exposure and menstrual cycle disruption.

PMID- 15251297
TI  - New concepts in organ transplantation.
AB  - Over the past several decades, many factors have led to higher rates of patient
      and graft survival in organ transplantation. These factors include enhanced
      immunosuppressants available in recent years such as Neoral, Prograf, sirolimus,
      mycophenolate mofetil and anti-interleukin-2 receptor monoclonal antibodies. In
      addition, other new drugs, such as FTY 720, FK 778, anti-CD20, anti-CD40, and
      anti-CH52 monoclonal antibodies, are now being tested in clinical studies.
      Furthermore, there have been advances in surgical techniques, such as the
      piggyback method without venovenous bypass, side-to-side anastomosis of the
      hepatic veins, use of vascular staplers, biliary duct-to-duct anastomosis with or
      without tube drainage, microsurgical hepatic artery anastomosis and laparoscopic
      donor nephrectomy. Finally, better patient and donor selection criteria with
      regard to HBV- and HCV-seropositive donors, diabetic donors, donors with
      malignancies, older donors, ABO-incompatible donors, and non-heart-beating donors
      have been combined with optimal timing of transplantation, better options for
      treating early surgical and late medical complications, and improved management
      in intensive-care units. Other noteworthy scientific and social development are
      on the horizon namely genetic advances in xenografting and cell transplantation,
      and induction of immunologic tolerance. This article reviews the current
      developments that have significantly improved graft and patient survival among
      solid-organ transplants.

PMID- 15251298
TI  - Alemtuzumab (Campath-1H) in allogeneic stem cell transplantation: where do we go
      from here?
AB  - Alemtuzumab (Campath-1H) has been widely used for T-cell depletion following both
      conventional and reduced-intensity conditioning allografts. We studied the impact
      of alemtuzumab used in vivo and in vitro on infections, immune reconstitution,
      and allograft outcome. The use of alemtuzumab in vivo following reduced-intensity
      conditioning and unrelated donor conventional transplantation was associated with
      durable engraftment and significant reduction in graft-versus-host disease (GVHD)
      but at the cost of impaired immune reconstitution and increased infectious
      complications. Alemtuzumab exposure in vitro was associated with durable
      engraftment and reduced GVHD following conventional transplants without affecting
      immune recovery to the same extent. Improved results were obtained following a
      further reduction in the alemtuzumab dose in vitro from 20 mg to 10 mg.
      Subsequent pharmacokinetic studies on alemtuzumab demonstrated that the antibody
      persisted at a higher concentration at the time of transplant and for at least 2
      months thereafter when used in vivo compared to persistence for less than 30 days
      when used at 20 mg in vitro. In this context; an antibody with a shorter half
      life, like the original rat CD52 antibody Campath-1G, would be preferable.
      Otherwise, our cumulative experience with alemtuzumab suggests that better
      results might be achieved by tailoring the dose and mode of antibody use to match
      the clinical situation. Further studies are needed to optimize the dose of
      alemtuzumab in vivo and in vitro, determined by the type of conditioning and the
      graft.

PMID- 15251299
TI  - New concepts in organ transplantation.
AB  - Long-term graft survival is the desired outcome of organ transplantation. The
      surrogate metric elimination of acute rejection episodes is not only inadequate
      but also deceptive, since this freedom does not promise long-term graft survival.
      Current clinical immunosuppressive agents have reduced acute rejection, but not
      prolonged graft survival. New paradigms in organ transplantation focus on
      adhesion-migration events using a selectin antagonist, an antisense
      oligonucleotide, and FTY 720; on peptide or allochimeric antigens on cytokine
      disruption, and on inhibition of costimulatory signals. Due to the array of
      adverse reactions to the available immunosuppressive drugs, these new approaches
      aim not only to augment long-term graft survival, but also minimize the
      associated toxicities.

PMID- 15251300
TI  - New concepts in organ transplantation.
AB  - Major progress has been made in clinical transplantation over recent years due to
      close cooperation between clinical specialists and academic investigators. High
      success rates are evident by longer patient and graft survivals. Treatment
      procedures have been integrated into fixed protocols utilizing new chemical
      immunosuppressive reagents that have improved the management of transplanted
      patients. Further developments in organ transplantation through better surgical
      techniques have allowed grafts of pancreas, lungs, and intestine. Current
      transplant medicine has, however, its limitations, especially in the context of
      the donor organ shortage, the toxicity of immunosuppressive drugs, the chronic
      rejection activity, and the inability to produce a state of immunologic
      tolerance. This paper sought to review new concepts in organ transplantation,
      especially concerning immunologic tolerance and the organ donor shortage.

PMID- 15251301
TI  - Pediatric organ transplantation and the hispanic population: approaching families
      and obtaining their consent.
AB  - BACKGROUND: While the number of children on waiting lists for organ donation
      continues to increase, little data exists concerning Hispanic children and organ
      donation. For physicians who care for Hispanic children, it is important to
      understand the factors that may influence organ donation in this population.
      METHODS: This retrospective chart review included 88 cases of brain death that
      occurred between 1990 and 1999 in 3 pediatric intensive care units. The data set
      included brain death determination, age, ethnicity, whether the family was
      approached for organ donation, and rate of consent. RESULTS: Compared with non
      Hispanic/Caucasian (NH/C) families, fewer Hispanic/Caucasian (H/C) families
      consented to organ donation (P < or = .03). H/C families were approached less
      often for organ donation than NH/C families, although the difference was not
      significant (P < or = .08). Even once approached, H/C families were probably less
      likely to consent to organ donation (P < or = .087). CONCLUSION: H/C families of
      children with brain death show a lower organ donation consent rate than do NH/C
      families. However, H/C families are less likely to be approached for organ
      donation and this may possibly explain the reason that fewer H/C families consent
      to organ donation.

PMID- 15251302
TI  - Ethical and legal aspects of organ transplantation in Iran.
AB  - The great advances in the technology of organ preservation, immunosuppression,
      and surgical procedures have resulted in success in saving lives. However, these
      advantages have raised major ethical, policy, and religious problems in organ
      transplantation. Extensive efforts have been made to address these problems in
      different communities. In this study the transplantation program and
      implementation of legislation in Iran is reviewed. The history of the organ
      transplantation "Act of Organ Transplantation and Brain Death," which allows
      controlled living unrelated donors access to renal transplantation, is discussed
      as the main subject.

PMID- 15251303
TI  - Influence of different sources of information on attitude toward organ donation:
      a factor analysis.
AB  - OBJECTIVES: To determine media through which the population receives information
      on donation; to analyze the association between the sources of information and
      the psychosocial variables with respect to the opinion on donation; and to
      determine how each source of information influences this opinion. MATERIALS AND
      METHODS: A questionnaire on donation was administered to a random sample of 2000
      persons stratified by age, gender, and geographical location, of whom 1143
      respondents claimed to have no experience with donation and/or transplantation. A
      statistical analysis was done between the sources of information or the
      psychosocial variables or their co-variation to determine their specific impact
      on the population. RESULTS: The medium with the greatest impact on the population
      is television; the second factor is the press and radio; the third is magazines
      and talks with friends/family; the fourth is hoardings and posters, and campaigns
      about organ donation; and the last factor is information given by health
      professionals. In the factor analysis between sources of information and
      psychosocial variables, an association was observed between press, radio, and
      information given by health professionals and a higher education level; and
      between information provided by discussions in schools, by age, and a higher
      level of education. Sources of Information sources as that have a favorable
      effect on donation include discussions, (P = .0079), and information by health
      professionals (P < .0005) and by friends (P = .0132) and by family (P = .0044).
      CONCLUSIONS: Opinion on donation is more favorable among subjects who have
      received information on an individual basis and at specialized meetings. The only
      psychosocial variable associated with some sources of information is the level of
      education.

PMID- 15251304
TI  - Cornea recipients: are their opinions and attitudes toward organ donation
      different from those of the general population?
AB  - BACKGROUND: Cornea transplantation provides a second chance for people with poor
      visual function. Unfortunately, there is a major shortage of donor cornea tissue.
      The purpose of this study was to evaluate the attitudes and willingness to donate
      organs among cornea transplant recipients. METHODS: Sixty-eight patients who
      underwent cornea transplantation between January 2002 and May 2003 were asked to
      complete a questionnaire dealing with their attitudes toward cornea and organ
      donation, and willingness to donate an organ. RESULTS: Religion was a
      contributing factor for a negative decision to donate organs. Only 29% of
      participants, most of whom were nonreligious were carrying a signed donation
      card. Fifty-eight percent of the patients knew that the cornea graft is derived
      from a deceased person; most of these patients were of European or American
      origin. Seventy-three percent knew that donation requires the agreement of a
      family member. Age, gender, marital status, and education were not significantly
      associated with attitude toward donation. CONCLUSION: Stronger efforts are needed
      by transplant coordinators, physicians, and nurses to improve the education and
      knowledge of patients and their families about the basic aspects of
      transplantation. Greater public awareness may increase the willingness to donate
      organs.

PMID- 15251305
TI  - Ethical and economical appreciation of living nonrelated donors renal
      transplantation from outside Turkey.
AB  - For patients with chronic renal failure organ demand has increased all over the
      world. Serious ethical problems have appeared with attempts to increase the
      number of organs from both living and cadaveric donors. The demand for
      transplantable organs is greater than the supply. The increasing number of
      patients waiting for transplantation has forced them to illegally obtain organs
      from living nonrelated donors (LNRD). This effort can result in serious
      complications for both recipient and donor. According to our regulations,
      commercial transplantation has been prohibited in Turkey, because of the
      possibility of abuse by an organ trade. In this study, we examine the
      complication, economics, and ethics concerning six patients operated outside our
      country.

PMID- 15251306
TI  - Pushing the envelope in renal preservation; improved results with novel perfusate
      modifications for pulsatile machine perfusion of cadaver kidneys.
AB  - INTRODUCTION: Novel preservation techniques may diminish ischemia/reperfusion
      (I/R) injury. Our preservation laboratory has modified Belzer MPS for machine
      perfusion (MP) with prostaglandin E1 (PGE 1), nitroglycerin (NTG), and
      polyethylene glycol-superoxide dismutase (PEG-SOD) to attenuate I/R injury. We
      reviewed our recent experience using this novel formulation (NF) compared with
      standard perfusates. RESULTS: Between January 1998 and March 2000, 1060
      consecutive kidneys were preserved in our laboratory. One hundred forty-eight
      kidneys (14%) were discarded. Fifty-eight percent of kidneys during this time
      period underwent MP (n = 532). En bloc kidney pairs were randomly assigned to
      pulsatile MP using Waters RM3 or MOX-100 perfusion systems using 1 of 3
      perfusates; NF (NF; n = 119), Belzer MPS (MPS; n = 201), or Belzer II albumin
      gluconate (ALB; n = 212) Significant improvements in delayed graft function (DGF)
      rate were seen with NF versus other perfusates (8% vs 14% vs 19%, respectively; P
      =.03). At 6 months, graft survival was significantly improved with NF compared
      with MPS and ALB (96% vs 90% vs 87%, respectively; P =.03). NF also produced a
      significantly higher percentage of recipients with a serum creatinine level < or
      = 1.5 mg/dL. CONCLUSIONS: Novel modifications of standard MP perfusate improved
      outcomes after renal transplantation. Preservation-based interventions targeted
      to ameliorate I/R injury can improve outcomes and may allow expansion of the
      donor pool.

PMID- 15251307
TI  - Protective effect of fructose-1,6-bisphosphate in the cold storage solution for
      liver preservation in rat hepatic transplantation.
AB  - Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on
      liver injury following ischemic/reperfusion periods. FBP maintains ATP levels and
      thereby cellular energy metabolism, which is important to the liver during cold
      preservation. In the present study, we evaluated the effects of FBP on the
      composition of storage solutions for cold liver preservation. Adult male Wistar
      rats were randomly divided into three experimental groups. Hepatic perfusion and
      preservation were performed with UW, UW plus 10 mmol/L FBP (UWM), and FBP 10
      mmol/L (FBPS) alone solutions. Biochemical measurements of AST, ALT, and TBARS
      were performed on samples of the cold storage solution at 0, 12, 18, and 24 hours
      preservation. FBPS and UW solutions showed similar preservation grades during 18
      hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a
      poor preservation grade. FBP appears to protect the liver from injury caused by
      free radicals when the preservation time is less than 18 hours. Therefore, FBP
      may exert a protective effect for the preservation of livers during cold storage,
      and could represent an important component of new cold storage solutions.

PMID- 15251308
TI  - Near-infrared spectroscopic assessment of mitochondrial oxygenation status-
      comparison during normothermic extracorporeal liver perfusion by buffer only or
      buffer fortified with washed red blood cells: an experimental study.
AB  - BACKGROUND: Use of marginal and non-heart-beating donors leads to an increased
      incidence of complications after clinical liver transplantation. Normothermic
      extracorporeal liver perfusion (NELP) may allow resuscitation and evaluation of
      such organs. Despite recent success in long-term liver preservation by NELP, no
      methods of organ evaluation have been defined. Mitochondrial cytochrome oxidase
      (Cyt Ox) levels reflect oxygen and substrate delivery, and hence ATP production
      at the cellular level. This study used near-infrared spectroscopy (NIRS) to
      measure Cyt Ox levels during NELP. METHODS: Livers retrieved from New Zealand
      white rabbits were immediately perfused in an extracorporeal circuit with
      oxygenated buffer (group A, n = 4) or red blood cell (RBC)-fortified buffer
      (group B, n = 4). Perfusion was continued for 3 hours at 37 degrees C pH 7.4, and
      perfusate was gassed with 95%O2/5%CO2 at 1 liter per minute. Cyt Ox levels were
      monitored continuously by NIRS and bile output was measured. RESULTS: Cyt Ox was
      reduced at the start of perfusion in both groups, but even more rapidly in the
      buffer-perfused group. After initial deterioration, Cyt Ox levels improved
      significantly (P < .05) with perfusion in the RBG-perfused group, but remained
      impaired in the buffer group 5.74 +/- 1.51 Deltamicromol/L and -25.77 +/- 21.94
      Deltamicromol/L for groups B and A, respectively, at 180 minutes. Differences in
      bile output were not significant (19.33 +/- 9.50 and 25.00 +/- 16.81
      micromol/min/100 g for groups B and A respectively). CONCLUSIONS: Cyt Ox levels
      may offer better viability markers than bile output. NIRS is a practical method
      to measure tissue oxygenation, and RBC-based perfusion provided better
      oxygenation during NELP.

PMID- 15251309
TI  - Assessment of liver function during extracorporeal membrane oxygenation in the
      non-heart beating donor swine.
AB  - INTRODUCTION: Although the use of non-heart beating donors (NHBD) could bridge
      the widening gap between organ demand and supply, its application to liver
      transplantation is limited due to warm ischemia (WI), biliary tree injury, and
      inadequate organ assessment. Warm blood reperfusion using extracorporeal membrane
      oxygenation (ECMO) can be a suitable option to reduce WI in organs from NHBD,
      allowing one to determine hepatic flow characteristics and bile production and
      facilitating assessment of organ viability. METHODS: This work evaluates the use
      of warm blood veno-arterial ECMO reperfusion in NHBD swine. Systemic and hepatic
      hemodynamics, bile, urine, and mixed venous blood were measured. After baseline
      data collection, 10 kU heparin was given intravenously followed by 1 g KCl to
      elicit cardiac arrest (CA). ECMO was started after 30 or 60 minutes of CA and
      kept running for 120 minutes. RESULTS: One-way repeated measures analysis of
      variance (ANOVA) with Tukey test analysis was used within a group. Two-way ANOVA
      was used between groups. ECMO can restore venous SO2 and pH in both groups; the
      values were close to baseline in the 30-minute CA group. Also, in this group,
      bile production was > 65% from baseline early during reperfusion and its value
      was lower in the longer CA group < 55% (P < .001). Aspartate aminotransferase
      (AST) was doubled at the end of ECMO support in the 60-minute CA group (P < .05).
      CONCLUSION: In this preheparinized NHBD swine model, ECMO support restores liver
      perfusion, oxygenation, and bile production after 60 minutes of CA.
      Quantification and analysis of bile production could be a determinant of liver
      function during ECMO resuscitation, and it may be a predictor of graft viability
      before transplantation.

PMID- 15251310
TI  - Histopathological and immunohistochemical detection of protective effects of
      University of Wisconsin solution supplemented with iloprost on donor lung damage.
AB  - OBJECTIVE: Histopathological evaluation and immunohistochemical markers of
      surfactant B and CD34 were used to detect alveolar type II cell and pulmonary
      endothelial cell damage in order to assess the efficacy on donor lung protection
      of University of Wisconsin (UW) solution supplementation with iloprost. METHODS:
      Twelve rats were divided into two groups: UW solution was used alone in group I,
      and UW iloprost solution in group II. Lung samples were taken at regular
      intervals for pathological examination to evaluate alveolar cell integrity with
      hematoxylin and eosin staining. Preservation, of alveolar type II cell and
      pulmonary endothelial cells was assessed using surfactant B and CD34
      immunomarkers, respectively. RESULTS: In both groups, alveolar integrity,
      surfactant, and CD34 revealed time-dependent, progressive damage, although this
      deterioration was less apparent among the iloprost-supplemented group. Alveolar
      integrity was better preserved at 4, 6, 8, 12, and 48 hours among group II rate.
      Surfactant staining showed significantly more deterioration at 12 and 24 hours in
      group I. Similarly, CD34 demonstrated significantly more injury at 6, 12, 24, and
      48 hours in group I. CONCLUSION: Although progressive lung tissue damage assessed
      by histopathological and immunohistochemical methods was observed in both groups,
      our findings suggest less deterioration in the iloprost-supplemented group.

PMID- 15251311
TI  - The fate of dendritic cells in a mouse model of liver ischemia/reperfusion
      injury.
AB  - Ischemia/reperfusion during liver transplantation triggers a complex cascade of
      inflammatory events that may lead to organ dysfunction. Herein, we investigated
      the consequences of hepatic ischemia/reperfusion on liver dendritic cells. Liver
      damage was documented by increased levels of serum alanine aminotransferase and
      by histopathology showing large areas of hepatocyte cytolysis. MHC class II+ CD45
      B220 F4/80 dendritic cells were detected in necrotic areas 20 hours after
      reperfusion. Dendritic cells freshly isolated from reperfused livers displayed a
      mature phenotype characterized by upregulated expression of B7 costimulatory
      molecules; MHC-class II, and CD1d molecules. As shown by real-time PCR, IL-10,
      and TGF-beta mRNA accumulated in liver dendritic cells isolated after
      reperfusion, whereas IL-12p40 mRNA levels were decreased and IFN-gamma mRNA
      levels were unchanged. These results suggest that hepatic ischemia/reperfusion
      results in maturation of dendritic cells, which preferentially produce inhibitory
      cytokines.

PMID- 15251312
TI  - Modulation of the NO pathway during short or prolonged blood reperfusion
      following ischaemia in a heterotopic rat heart transplantation model.
AB  - Ischemia-reperfusion injury plays a major role in graft dysfunction following
      transplantation. Extensive research has demonstrated that nitric oxide (NO) plays
      a fundamental role to protect the heart against this injury. Consequently, we
      quantified NO synthase (NOS) isoform protein levels in a rat heart transplant
      model during short and prolonged reperfusion following ischemia. Experiments were
      performed using a modified Lewis to Lewis heterotopic abdominal heart
      transplantation with a total ischemic time of 3 hours followed by 1 or 24 hours
      of blood reperfusion (n = 12). Heart function, as represented by the rate
      pressure product, increased from 7912 +/- 489 to 27067 +/- 9982 mm Hg/min (mean
      +/- SEM, short vs prolonged reperfusion, P = .0027). NOS isoform protein levels
      determined using Western blotting of freeze-clamped hearts were compared to
      baseline values. eNOS protein levels were significantly lower during short
      reperfusion compared to the basal value (P = .0077) or to prolonged reperfusion
      (P = .004), returning to the basal value after 24 hours of reflow. iNOS protein
      was not detected in the basal condition or after 1 hour of reflow, but was
      present after 24 hours of reflow (P = .0001 vs basal value and 1-hour reflow).
      nNOS protein was 69% lower after 1 hour of reflow compared with the baseline
      value (P = .0001), it was not restored after 24 hours of reflow (P = .002). These
      results suggest involvement of the NO pathway in ischemia-reperfusion injury with
      distinctive roles of NOS isoforms during short and prolonged reperfusion
      following ischemia.

PMID- 15251313
TI  - Keeping up with the Jones's: open donor nephrectomy in the laparoscopic era.
AB  - Several new approaches have been developed to perform donor nephrectomy. These
      include laparoscopic donor nephrectomy and open donor nephrectomy performed
      through small incisions, herein referred to as "mini-open donor nephrectomy". In
      the past, we performed open donor nephrectomy via a standard flank incision. In
      October 2002, we introduced mini-open donor nephrectomy via an anterior,
      retroperitoneal approach. Contemporaneously, we offered the option of
      laparoscopic donor nephrectomy. Herein, we review our single-center experience
      with these three techniques. Mini-open donor nephrectomy was comparable to the
      laparoscopic approach for duration of narcotic requirement and donor length of
      stay. The laparoscopic procedure was more expensive. Both procedures demonstrated
      improvement over the flank approach by eliminating the risk of pneumothorax,
      neuropathy, and flank bulge. In addition, length of stay and narcotic
      requirements were higher with the flank approach. Mini-open donor nephrectomy
      provides a good alternative to laparoscopic surgery, offering the donor an
      equivalent convalescence at lower cost and potentially with reduced morbidity.

PMID- 15251314
TI  - Transplantation of a cadaveric polycystic kidney in a patient with autosomal
      dominant polycystic kidney disease: long-term outcome.
AB  - INTRODUCTION: Kidneys from donors affected by autosomal dominant polycystic
      kidney disease (ADPKD) were considered unusable for transplantation. To the best
      of our knowledge, seven cases worldwide have now been described in the English
      literature since 1967 suggesting such donor organs may be acceptable under
      certain conditions. Most of these reports have only short-term follow-up.
      METHODS: We provide a review of these patients and share our experience with an
      ADPKD patient who had a cadaveric ADPKD transplant and has been closely followed
      for 10 years. RESULTS: During the 10-year period, the patient had three
      transplant biopsies without complication. This creatinine is currently 1.2 mg/dL.
      Serial computed tomography imaging indicated that the cystic disease slowly
      progressed during this time period. He eventually developed intractable pain in
      his native left kidney and underwent a laparoscopic nephrectomy. CONCLUSIONS:
      Normal functioning cadaveric kidneys that show early signs of polycystic kidney
      disease should be considered acceptable for renal donation. These organs provide
      the recipient a safe, reasonable period of graft survival and have not been shown
      to cause adverse effects.

PMID- 15251315
TI  - Pilot study of the optimum hematocrit for patients in the predialysis stage after
      renal transplantation.
AB  - Anemia is a common complication in patients with chronic kidney diseases
      including posttransplant patients. Guidelines for the treatment of anemia in
      chronic kidney disease published by NHF-K/DOQI recommend the target hemoglobin
      and hematocrit (Hb and Ht) levels to be in the 11 to 12 g/dL and 33% to 36%
      ranges, respectively, which are somewhat higher than those recommended in Japan
      (Ht = 30%). However, these guidelines were established mainly from the data on
      hemodialysis patients with only limited information available as to the impact of
      anemia control in posttransplant patients. The aim of the present study was to
      evaluate cardiac function and quality of life (QOL) when the Ht was raised to
      about 36% by administration of recombinant-human-erythropoietin (rHuEPO) to
      patients with mild impairment of renal function (s-Cre < 2.0 mg/dL) after renal
      transplantation. Twenty-five patients were analyzed for cardiac function, blood
      data, and QOL in a prospective study encompassing 8 months of rHuEPO treatment.
      Using a once weekly subcutaneous dose of 6000 IU of Epoetin-beta, the Ht became
      33% to 36% and Hb was 11 to 12 g/dL. Among the cardiac function tests, left
      ventricular end-diastolic diameter and left ventricular mass index decreased
      significantly. QOL did not show any significant changes after administration of
      rHuEPO. In conclusion, we demonstrated a potential benefit of using rHuEPO to
      maintain the Hb between 11 and 12 g/dL and the Ht between 33% and 36% in
      posttransplant patients with regard to the prevention of cardiovascular
      complications. Further study is required to establish the benefits of correcting
      anemia by rHuEPO on the outcome of posttransplant patients.

PMID- 15251316
TI  - Predictors of bone mineral density in patients on hemodialysis.
AB  - Renal osteodystrophy is a universal complication of uremia. Renal failure
      patients are at risk for low bone mineral density (BMD) and fractures.
      Parathyroid hormone (PTH) plays a pivotal role in the pathophysiology of uremic
      bone disease. Histomorphometric studies suggest that the maintenance of PTH
      levels between two and four times the upper limit of normal is associated with
      the lowest prevalence of two common forms of osteodystrophy: osteitis fibrosa
      cystica and adynamic bone disease. The purpose of this study was to investigate
      whether the above recommendation for PTH levels in dialysis patients corresponds
      to a more optimal BMD with a special emphasis on diabetic versus nondiabetic
      subjects. Twenty-eight patients with chronic renal failure on hemodialysis
      underwent measurement of PTH levels, as well as BMD at the lumbar spine, hip, and
      forearm. They were divided into three groups based on the mean PTH level over the
      5 years prior to having BMD measured. Osteoporosis was diagnosed in 55% of men
      and 87% of women on dialysis. Predictors of BMD were gender, duration on
      hemodialysis, and diabetes. Our study supports the histomorphometry-based studies
      suggesting that the maintenance of intact PTH levels two to four times the upper
      limit of normal may be associated with better skeletal health in uremic patients
      on hemodialysis, and that the diabetic subgroup is at particular risk for low
      BMD.

PMID- 15251317
TI  - Major histocompatibility complex class I and II antigens frequencies in Baloch
      ethnic group living in the southeast region of Iran.
AB  - BACKGROUND: Human leukocyte antigens have become key components to investigate
      the genetic relationships between populations. OBJECTIVE: The aim of this study
      was to determine the genetic diversity of HLA class I and II alleles among the
      Baloch ethnic group of southeastern in comparison with the Parsi ethnic group,
      thereby establishing a database for further investigations on the ancestry and
      genetic factors contributing to complex diseases in this region. MATERIALS AND
      METHODS: Thirty unrelated Balochi individuals from southeast Iran and 108 Parsi
      unrelated individuals were serologically typed using standard microcytotoxicity
      assays with commercial and local trays. RESULTS: The most frequent class I
      alleles of the Baloch ethnic group were HLA-A01 (53.3%), -A02 (30%), -A09
      (23.3%), -A11 (20%), -A23 (23.3%), -B05 (53.3%), and -B08 (26.7%). The class II
      alleles more frequently observed were HLA-DR1 (26.7%), -DR2 (43.3%), -DR3 (20%), 
      DR4 (33.3%), -DR7 (26.7%), -DR11 (33.7%), -DRw52 (83.3%), -DRw53 (36.7%), -DQ1
      (46.7%), -DQ2 (20%), and -DQ3 (40%). In contrast with the Parsi ethnic group, the
      frequencies for the following alleles were significantly higher in Baloch than
      Parsi. HLA-A01, -A23, -A25, -B05, -B08, -B16, -B17, -B60, -DR14, -DQ4, and -DQ7.
      In contrast, the frequencies of HLA-Cw4 and -DQ3 alleles in the Parsi were
      significantly higher than the Baloch ethnic group. CONCLUSIONS: This first study
      of HLA in widely dispersed areas of Iran represents an important resource for
      investigators in the fields of transplantation immunology and population
      genetics.

PMID- 15251318
TI  - Beneficial effect of concomitant induction with antilymphoblast globulin,
      cyclosporine, and steroids on long-term renal allograft outcome.
AB  - BACKGROUND: The addition of induction therapy with antilymphocytic antibodies to
      cyclosporine (CsA) based immunosuppression, has reduced acute rejection incidence
      and improved short-term survivals, but has not had well-established effects on
      long-term renal transplant survival. PATIENTS: We analyzed the long-term
      allograft outcome of patients included in a prospective randomized clinical study
      conducted in our center 15 years ago by comparing two strategies: (A) horse
      antilymphoblast globulin (ALG) given at 10 mg/kg on alternate days to a maximum
      of 6 doses with low-dose CsA started at 8 mg/kg per day and prednisone at 0.25
      mg/kg per day, versus (B) CsA started at 15 mg/kg per day and prednisone at 0.5
      mg/kg per day. Diabetic and highly sensitized patients (PRA > 70%) were excluded
      from the study. RESULTS: The characteristics of the 50 patients enrolled in each
      group were not different. Although patient survival was not different (88% in
      group A vs 77% in group B), recipients treated with ALG showed a lower incidence
      of acute rejection episodes (20% vs 44%, P = .01) and better death-censored renal
      allograft survival (57% vs 41%, P = .03). Among rejection-free patients, graft
      survival was 15% higher in group A (60% vs 45%, P = .12). Multivariate Cox
      regression analysis showed that an acute rejection episode (relative risk [RR]:
      2.44, 95% confidence interval [CI] 1.36-4.39; P = .0029) rather than ALG
      immunosuppression (RR 0.74, 95% CI 0.41-1.33; P = NS) was an independent
      predictor of death-censored graft survival. CONCLUSIONS: In summary, we confirmed
      that concomitant induction therapy with ALG, CsA, and steroids improves long-term
      renal allograft survival.

PMID- 15251319
TI  - Medical and surgical aspects of pediatric renal transplantation using living
      donors.
AB  - The outcomes of 19 consecutive living-donor renal transplants (LD-RTx) was
      compared with 41 cadaveric grafts (CD-RTx) performed at our institution using
      basiliximab, cyclosporine, and prednisone as standard immunosuppression. LD-RTx
      significantly shortened the waiting time on dialysis. However, patient survival
      (100% in both groups), 1-year graft survival (94.7% vs 90%), and rejection-free
      graft survival (76.9% vs 73.5%) was not significantly different. LD-RTx showed
      better glomerular filtration rates in the early phase after transplantation, a
      difference that faded with time. Graft function was similar after 1 and 2 years.
      LD grafts with double renal arteries were used successfully in four cases;
      heparin therapy was administered to avoid graft thrombosis. A significantly
      greater number of lymphoceles was observed with LD grafts (7/19 vs 1/41, P <
      .01). In conclusion with improved immunosuppression producing better results with
      CD grafts, the advantages of LD-RTx have vanished. LD grafts with double arteries
      may be used successfully and LD-RTx allows a shorter dialysis period. The high
      incidence of lymphoceles in our series awaits further evaluation.

PMID- 15251320
TI  - The FcgammaRIIa polymorphism in patients with chronic kidney graft rejection.
AB  - The FcgammaRIIa receptors, which provide a crucial link between cellular and
      humoral components of the immune response, display allelic polymorphism.
      Individuals are homozygous for either arginine 131 (RR131) or histidine 131
      (HH131) or are heterozygous for these two alleles (RH131). The HH131 genotype
      binds human IgG2 with high RR131 with low, and RH131 with intermediate affinity.
      The aim of the study was to evaluate the FcgammaRIIa polymorphism in patients
      with chronic kidney graft rejection. The study included 121 renal transplant
      recipients: 53 patients with long-term stable graft function and 68 with chronic
      allograft rejection. The distribution of FcgammaRIIa genotypes in patients with
      chronic kidney graft rejection did not differ significantly from that in patients
      with stable graft function. The results suggest that the FcgammaRIIa polymorphism
      is not an important genetic risk factor for chronic rejection of kidney
      allografts.

PMID- 15251321
TI  - Risk factors for graft loss in patients with recurrent IGA nephropathy after
      renal transplantation.
AB  - BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys
      has been reported to be >50%. Although recurrent IgAN has a benign clinical
      course, recent data suggest that it leads to graft loss in a substantial number
      of patients. METHODS: We performed a retrospective single-center analysis of 34
      renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage
      renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients,
      of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN.
      Recurrent transplant IgAN was more often detected in men and at later timepoints
      after post-transplantation. Four patients with recurrent transplant IgAN
      progressed to graft failure. Progression to graft failure was associated with
      worsened renal function, higher systolic blood pressure, and the lack of
      presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of
      allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA
      typing, and immunosuppression did not show a relation to recurrence or graft
      loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft
      survival and risk factors for graft loss due to recurrent IgAN were similar to
      those among IgAN in native kidneys.

PMID- 15251322
TI  - Evaluation of the new heterogeneous ACMIA immunoassay for the determination of
      whole-blood cyclosporine concentrations in bone marrow, kidney, heart, and liver
      transplant recipients.
AB  - Cyclosporine (CyA) has a narrow therapeutic index. Determination of CyA
      concentrations correlate with rejection or adverse effects like nephropathy.
      Cyclosporine is assayed based on either chromatographic or many different
      immunoenzymologic techniques. The investigators evaluated a new heterogeneous
      immunoassay of CyA on RxL Dimension. The pretreatment step is automatically
      performed in the apparatus. Linearity, intra- and interday precision, limit of
      quantification, dilutions, and stability of the equipment were compared with the
      EMIT method for patient determinations. The heterogeneous immunoassay showed a
      good linearity between 0 and 500 ng/mL, and intra- and inter-day precision with a
      coefficient of variation below 9.2%. The investigators observed reproducible and
      accurate dilutions of high concentrations (500 to 2000 ng/mL). The correlation
      with the EMIT technique was valid: ACMIA = 0.964 EMIT + 0.156 (r = .96) for
      different types of transplant (n = 116). Finally, this new system improves the
      determination of CyA concentrations.

PMID- 15251323
TI  - Variable cyclosporine exposure: a risk factor for chronic allograft nephropathy
      and graft loss?
AB  - BACKGROUND: Following the introduction of ciclosporine (CsA), the 2-year survival
      of transplanted kidneys improved from less than 60% to over 80%. Though the
      introduction of this drug resulted in a marked improvement in graft survival, its
      use was not without problems. Variable absorption and a narrow therapeutic index
      resulted in the need for measurements of CsA blood concentrations to tailor the
      drug dose to maximize therapeutic efficacy while minimizing toxicity. METHODS:
      Data were available from the LOTESS study of 4948 transplant patients receiving
      Neoral with at least 5 years' follow-up. Potential risk factors associated with
      outcome in renal transplant recipients treated with CsA were explored: the
      primary outcome variable was graft loss. A stepwise binary logistic regression
      analysis was used to identify donor, recipient, and treatment variables related
      to outcome. RESULTS: In the initial analysis, chronic rejection was the only
      significant predictor of graft loss. The relative risk (RR) of graft loss was
      16.9 (95% CI = 13.9-20.4). Further analysis identified four independent risk
      factors for chronic rejection cadaveric donor (RR, 1.50; 95% CI = 1.05-2.15),
      older donor (RR, 1.02; 95% CI = 1.01-1.02), younger recipient (RR, 1.02; 95% CI =
      1.02-1.03), and variable predose CsA concentration (RR, 1.25; 95% CI = 1.06
      1.48). CONCLUSION: With the UK kidney transplant waiting list at about 5000
      patients and only 1658 transplants performed during 2002, it is important
      maximize graft survival. For example, perhaps marginal donors (age > 55) can be
      matched to older recipients without increasing the risk of chronic allograft
      nephropathy and therefore graft loss. Variable predose CsA concentrations may
      arise from at least three different sources: adherence to treatment, drug
      formulation, and individual variation in absorption. Therefore, it is important
      to emphaze to patients that erratic compliance may increase their risk of graft
      loss. Second, although only one CsA formulation is marketed in the UK, when
      generic forms of CsA are introduced it will be important to demonstrate
      consistent delivery of CsA from these new formulations. Third, improved
      monitoring of CsA using a C2 rather than a predose blood concentration
      measurement may be used to reduce intra-individual variations in drug exposure.

PMID- 15251324
TI  - Age-dependency of mycophenolate mofetil dosing in combination with tacrolimus
      after pediatric renal transplantation.
AB  - BACKGROUND: Dosing of mycophenolate mofetil (MMF) must be lower in combination
      therapy with Tacrolimus (Tac) than with Cyclosporine. One study with mostly
      adolescent recipients recommended an MMF dose of 250 mg/m2 BID. Because this dose
      resulted in low area-under-the-curve (AUC) in our infant population, we
      retrospectively analyzed all available pharmacokinetic (PK) profiles in pediatric
      renal transplant patients on MMF plus Tac therapy to propose appropriate MMF
      dosing in pediatric patients of all ages. PATIENTS AND METHODS: Forty-four PK
      profiles were performed in 27 patients (median age, 11.6 years; range, 1.8-20.7
      years). The investigations were performed at a median of 299 days (range, 24
      3424) after transplantation. Ten patients were converted to Tac plus MMF, all
      others received this as primary therapy. For patients with repeated measurements,
      we calculated the average AUC and doses. We used first-order PK modeling to
      calculate the doses for a mycophenolic acid (MPA) AUC of 60 ug*h/mL and a Tac AUC
      of 150 ng*h/mL. RESULTS: The mean Tac dose was 2.6 +/- 1.2 mg/m2/d or 0.086 +/-
      0.038 mg/kg/d, resulting in an average AUC of 120.6 +/- 30.4 ng*h/mL. The MMF
      dose was not normally distributed; the median dose was 549 mg/m2/d (range, 146
      1413) and the median MPA AUC was 49.8 ug*h/mL (range, 26.7-156.0). The mean dose
      for a Tac AUC of 150 ng*h/mL was 3.50 +/- 1.77 mg/m2/d (0.117 +/- 0.058 mg/kg)
      and was independent of age or time after transplantation. By contrast, we found a
      negative relationship between the dose per m2 (r2 = 0.29; P = 0.0038) or per kg
      (r2 = 0.58; P < .0001) required for an MPA AUC of 60 ug*h/mL and patient age.
      Converted and primary patients behaved identically. The dosing requirement
      decreased from 500 mg/m2 BID in 2-year-old patients to 250 mg/m2 in adolescents.
      There was substantial interpatient variability of 44%. CONCLUSIONS: Higher MMF
      doses are required for young children. Our data suggest a starting dose for
      infants of 500 mg/m2 BID, with PK monitoring of MPA due to substantial
      interpatient variability.

PMID- 15251325
TI  - Conversion from tacrolimus to cyclosporine for a non-dose-dependent tacrolimus
      induced toxicity, a pediatric kidney transplant recipient case report.
AB  - Tacrolimus-induced toxicity is considered a dose-related side effect largely due
      to a direct action of this potent calcineurin inhibitor on its targets including
      the kidney and the pancreas. This paper describes a case of tacrolimus systemic
      toxicity that appeared in a pediatric kidney transplant recipient who received a
      low drug dose. The kidney biopsy was a crucial aid toward the correct diagnosis,
      which reversed upon conversion to cyclosporine-based immunosuppression. A review
      of the literature suggests a chance of systemic toxicity even when the patient is
      maintained on therapeutic levels of tacrolimus. Because idiosyncratic reactions
      to the drug have not yet been postulated, we conclude that this suspicion may be
      addressed by a safe conversion to cyclosporine in pediatric patients.

PMID- 15251326
TI  - Immunological monitoring of posttransplant allograft sensitization following
      living related donor renal transplantation.
AB  - A better understanding of the immunobiological processes and predictors of graft
      rejection holds promise for development of new therapeutic strategies and also
      for individualization of immunosuppression. The objective of this study was to
      analyze the clinical relevance of immune parameters, such as recipient
      sensitization status, donor-specific antibodies, and anti-HLA antibodies, which
      are major predictors of graft outcome following renal transplantation. Sera from
      264 renal recipients at different posttransplant period were included for
      detection of anti-donor antibodies (by flowcytometry); anti-HLA, antibody (by
      ELISA), and panel-reactive antibodies (PRA) by complement-dependent cytotoxicity
      (CDC) methods. Graft survival was analyzed in relation to posttransplant PRA at 2
      years follow-up time: overall survival was significantly compromised in the
      highly sensitized group (group III) compared to the other two groups (overall
      chi2 = 24.20, P = 5.5 x 10(-06)). Flow cytometric cross-matches revealed the
      presence of anti-donor class I antibodies (T+) in 39 patients who had a poor
      graft survival of 51% compared with 85% survival in 225 antibody-negative
      patients. (chi2 = 22.260, P = 2.381 x 10(-.06)). Further analysis was performed
      based on the presence or absence of FCXM and ELISA-detected antibodies.
      Recipients belonging to group I (ELISA+/FCXM+) showed significantly lower graft
      survival (43%) compared with that observed in group II, which were essentially
      nonsensitized individuals (90%; P = 3.1 x 10(-08)). The graft survival in the
      ELISA-/FCXM+ group was 63%, which was significantly lower than that in group II
      (P = 5.14 x 10(-03)). Group IV (ELISA+/FCXM-) including 38 (14%) serum samples
      with nondonor but HLA-specific antibodies was associated with significantly
      poorer graft survival (63%) compared with group II (P = 6.6 x 10(-05)). Our data
      also show that while FCXM is the most sensitive test to detect donor-specific
      antibodies, the ELISA method offers the additional advantage of detecting anti
      HLA class-I antibodies, which are detrimental for renal graft survival. Thus the
      use of multiple parameters to assess recipient immune profile can predict graft
      outcome more accurately thus helping the individualization and optimization of
      immunosuppression.

PMID- 15251327
TI  - Expression of TRAIL, DR4, and DR5 in kidney and serum from patients receiving
      renal transplantation.
AB  - Renal transplantation is the best treatment of some end-stage renal diseases.
      Unfortunately, not every transplant is successful due to the rejection or
      dysfunction of the transplanted kidney. Many cytokines participate in rejection
      by inducing inflammation or apoptosis. In this study, the expressions of TRAIL,
      DR4, and DR5 in rejected renal tissue and of serum soluble TRAIL (sTRAIL) in
      patients with kidney rejection were investigated by immunohistochemical staining
      and sandwich enzyme-linked immunosorbent assay, respectively. The results showed
      that the expression of TRAIL, DR4 and DR5, and serum sTRAIL levels were markedly
      upregulated among renal transplant patients. Since both membrane and soluble
      forms of TRAIL can induce apoptosis of DR4/DR5-expressing cells via recruiting
      FADD and caspase 8, elevated TRAIL and its receptors may participate in renal
      graft rejection.

PMID- 15251328
TI  - Molecular monitoring of organ recipients from cancer-affected donors by detection
      of circulating tumor cells.
AB  - We have initiated regular molecular monitoring based on nested RT-PCR detection
      of circulating tumor cells for monitoring recipients of organs from cancer
      affected donors in Italy (in the context of a "Donation Safety and Donated Organ
      Quality" project organized by the Centro Nazionale Trapianti). Five patients are
      being monitored. For two patients who each received a kidney from a single donor
      with prostate adenocarcinoma, RT-PCR was performed using PSA mRNA. For three
      recipients of organs (two livers and one kidney) from donors with renal cell
      carcinoma, RT-PCR was performed using cytokeratine 18 and 19 mRNA. Blood samples
      from five healthy subjects were used as negative controls. After a median
      monitoring time of 26 months (range 8 to 32), none of the regular 3-month assays
      has tested positive. This pilot study suggests that detection of circulating
      tumor cells by nested RT-PCR may provide a feasible molecular monitoring, which
      might assist decision making regarding other forms of clinical surveillance.

PMID- 15251329
TI  - Prediction of renal allograft function with early Doppler ultrasonography.
AB  - INTRODUCTION: Doppler ultrasonography (USG) is an useful, noninvasive diagnostic
      tool for the management and follow-up of the transplanted kidney. However, it is
      believed that the value of Doppler USG is limited to discrimination of acute
      rejection episodes. We tested whether early Doppler USG findings were predictive
      of 1-month and 1-year allograft functions in noncomplicated renal transplant
      recipients (RTRs). PATIENTS AND METHODS: Resistive index (RI) and pulsatile index
      (PI) values obtained by doppler USG within the first week of transplantation were
      correlated with allograft function at 1 month and 1 year in 45 (10 women, 35 men,
      mean age: 27 years) noncomplicated cases. Patients with complications during the
      first posttransplant year were not included. RESULTS: There was a negative
      correlation between both RI and PI with creatinine clearance values at 1 month
      and at 1 year posttransplant. There was a significant decline in allograft
      function among cases with either RI > or = 0.7 or PI > or = 1.1. Patients with
      impaired allograft function have higher RI and PI values. CONCLUSION: Renal
      allograft survival is influenced by many factors. However, no reliable simple
      parameter has been identified to predict long-term outcome. Doppler USG performed
      during the early transplantation period with calculation of RI and PI may have a
      predictive value to forecast early and long-term outcomes of noncomplicated
      kidney transplants.

PMID- 15251330
TI  - Ambulatory blood pressure monitoring in renal transplant patients: modifiable
      parameters after active antihypertensive treatment.
AB  - BACKGROUND: Hypertension (HT) accounts for nearly 60% to 80% of renal transplant
      patients (RT). It is one of the most important risk factors for cardiovascular
      diseases and may cause chronic graft dysfunction. Therefore, it is important to
      accurately detect and treat HT. We aimed to evaluate the changes in ambulatory
      blood pressure monitoring (ABPM) parameters among hypertensive RT after active
      treatment compared with baseline values. METHODS: Thirty seven RT (25 men, 12
      women, aged 49.4 +/- 11.2 year) diagnosed with mild to moderate HT underwent 24
      hour ABPM after a 4-week washout period (W0). For the 23 RT with confirmed HT of
      a second 24-hour ABPM was recorded after 4 weeks of treatment with doxazosin GITS
      (-4 mg once daily in the morning), a new formulation of an alpha1-receptor
      inhibitor (W4). Nondippers were considered when mean blood pressure (BP) showed a
      < or = 10% reduction during sleep. Statistical analyses included Saphiro-Wilks
      test, Student t test, and ANOVA. RESULTS: After active treatment systolic,
      diastolic, and mean BP (SBP, DBP, MBP) significantly decreased during diurnal and
      24 hours but not the nocturnal period. No significant change was observed for
      heart rate nor for pulse pressure during any period. The prevalence dippers
      increased from 0% to 17% after treatment. After placebo administration 8 among 37
      RT with HT diagnosed according to casual BP remained hypertensive at nighttime
      (but not at daytime) according to 24-hour ABPM. CONCLUSIONS: Diurnal and 24-hour
      periods of ABPM showed significant changes in SBP, DBP, and MBP after active
      treatment with doxazosin GITS. No significant BP changes were observed in the
      nocturnal period or in dipper status. Further studies using ABPM must be
      undertaken to determine the optimal dosage and time of administration of
      antihypertensive drugs in RT.

PMID- 15251331
TI  - Ambulatory blood pressure monitoring in children after renal transplantation.
AB  - Arterial hypertension is a common complication in children after renal
      transplantation and the control of hypertension is often difficult. This
      retrospective investigates the prevalence and rate of control of hypertension
      using ambulatory blood pressure monitoring (ABPM) in 45 children (mean age 14.1
      +/- 4.3 years, mean time after renal transplantation 2.2 +/- 2.7 years), all on
      cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil plus daily
      steroids. The overall prevalence of hypertension was 82%. None of the
      transplanted children had normal blood pressure without antihypertensive therapy
      (ie, spontaneous normotension). Twenty percent of children had untreated
      hypertension, 18% had controlled hypertension, and 62% had uncontrolled
      hypertension. Prevalence of the nondipping phenomenon was 53%. The mean number of
      antihypertensive drugs (without diuretic monotherapy) in treated patients was 1.9
      drugs per patient. The prevalence of arterial hypertension in children after
      renal transplantation is high and the control of hypertension is often
      unsatisfactorily low.

PMID- 15251332
TI  - Endothelial dysfunction in renal transplant patients is closely related to serum
      cyclosporine levels.
AB  - BACKGROUND: Cyclosporine (CsA), one of the standard agents used in renal
      transplant recipients, has been considered to cause endothelial dysfunction and
      to contribute to arterial complications posttransplant. Since concentration
      dependent effects of CsA on endothelial functions in humans have not been
      examined, this study was performed to investigate this relationship. METHODS:
      Fifteen renal transplant patient and 20 healthy subjects (controls) were
      evaluated for brachial artery endothelial function using high-resolution vascular
      ultrasound just before the CsA dosage (baseline) and at the second hour after the
      administration. Endothelium-dependent and -independent vasodilatations (EDD and
      EID, respectively) were assessed by establishing of the responses to reactive
      hyperemia and by using sublingual nitroglycerine, respectively. CsA levels were
      assessed at baseline and at second hour, times when performing brachial artery
      measurements. RESULTS: There were no significant differences between recipients
      and controls with respect to atherosclerosis risk factors. Mean EDD of recipients
      at baseline times were significantly less than those in controls (9.1% +/- 5.5%
      vs 15.2% +/- 7.2%, respectively; P < .001). CsA levels at trough and at second
      hour were 153.9 +/- 74.8 ng/mL and 646.8 +/- 163.2 ng/mL, respectively (P <
      .0001). Recipient, EDD at second hour was significantly reduced compared to
      baseline values (5.3% +/- 3.6% vs 9.1% +/- 5.5% respectively; P = .014) while
      changes in EID and in the diameter of the brachial artery between baseline and
      second hour were insignificant. CONCLUSION: Endothelial dysfunction evaluated by
      brachial ultrasound in renal transplant recipients is closely related to CsA
      levels. It is more pronounced at 2 hours after CsA dosage, at the time of peak
      drug levels.

PMID- 15251333
TI  - Does the endothelial function change in renal transplant patients with longer
      duration of exposure and with higher cumulative doses of cyclosporine?
AB  - OBJECTIVE: Administration of cyclosporine (CsA) is one potential cause of
      endothelial dysfunction in renal transplant patients. We sought to investigate
      endothelial functional changes with respect to the cumulative dose and duration
      of exposure to CsA. METHODS: Sixty-six renal recipients and 25 healthy controls
      were included in the study. The recipients were classified according to their
      time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months); and
      group 3 (over 72 months). Endothelial function of the brachial artery was
      evaluated using high-resolution vascular ultrasound. Endothelium-dependent and 
      independent vasodilatation (EDD and EID, respectively) were assessed by assessing
      the responses to reactive hyperemia and using sublingual isosorbide dinitrate
      (ISDN), respectively. RESULTS: There were no statistically significant
      differences between the groups with regard to their demographic, clinical, and
      most biochemical characteristics. Baseline measurements of the diameter of the
      brachial artery were similar in all groups. The values of mean brachial artery
      EDD and EID responses in groups 1, 2, and 3 were less than those in the control
      group (P < .05, P < .05, and P < .05, respectively). Mean brachial artery EDD and
      EID in group 1 were significantly impaired compared to groups 2 and 3 (for EDD: P
      < .05 and P < .05, respectively; for EID: P < .05 and P < .05, respectively). In
      contrast there was no difference between groups 2 and 3 with respect to these
      parameters. There were mild to moderate positive correlations between the
      cumulative doses of CsA and EDD and EID (r = .26 and r = .52, P < .05,
      respectively). CONCLUSION: Endothelial dysfunction was more prominent in the
      first 36-month period than later despite the longer exposure to and higher
      cumulative doses of CsA. This finding may reflect an extended effect of the
      uremic state on endothelial function or more intense doses of CsA in early
      posttransplant period.

PMID- 15251334
TI  - Abnormal kinetics of erythrocyte sodium lithium countertransport in renal
      transplant recipients.
AB  - Cardiovascular disease is now the most common cause of death in renal
      transplantation. Cyclosporine (CsA)-associated hypertension might be a major
      cause of cardiovascular risk factors. There is evidence suggesting that one
      mechanism of CsA toxicity might be mediated through alteration of membrane lipid
      peroxidation, which can activate cellular pathways. Erythrocyte sodium lithium
      countertransport (Na/Li CT) is a sensitive membrane protein that is abnormal in
      several hypertensive-related diseases. We have studied the kinetics of
      erythrocyte Na/Li CT in 38 renal transplant recipients. Group 1 (15 patients)
      received CsA, azathioprine, and prednisolone (C+A+P), Group 2 (15 patients) CsA
      and prednisolone (C+P), and Group 3 (8 patients) azathioprine and prednisolone
      (A+P). Compared with the normal subjects, the Michaelis constant for
      extracellular sodium (Km) of erythrocyte Na/Li CT was lower among the CsA-based
      regimen groups (C+A+P and C+P), but not the A+P group. The maximum velocity
      (Vmax)/Km ratio was also higher among the C+A+P and C+P groups than the A+P
      group. These abnormalities of Na/Li CT kinetics might be due to abnormalities of
      cell membrane functions, caused by immunosuppressive drugs, particularly CsA.
      Further studies involving the effect of CsA on the physiological function of
      membrane thiol proteins are required.

PMID- 15251335
TI  - Effect of colchicine on cyclosporine nephrotoxicity, reduction of TGF-beta
      overexpression, apoptosis, and oxidative damage: an experimental animal study.
AB  - BACKGROUND: Proinflamatory and profibrotic cytokines may be responsible for the
      cyclosporine A nephrotoxicity. Increased levels of apoptosis, free oxygen
      redicals, and transforming growth factor beta (TGF-beta), may play an important
      roles in the pathogenesis of nephrotoxicity. In this experimental animal study,
      we sought to investigate the effects of colchicine on the cyclosporine
      nephrotoxicity. METHOD: Twenty-four Wistar albino rats were divided into three
      groups: cyclosporine 15 mg/kg subcutaneously (SC); cyclosporine 15 mg/kg SC plus
      colchicine 30 mcg/kg orally; and a control group; equal doses of olive oil orally
      were administered to groups 1, 2, and 3. Renal function, cyclosporine levels, and
      serum malonyldialdehyde (MDA) levels were measured at the end of 4 weeks.
      Apoptosis, TGF-beta, and other findings were detected in renal tissue with the
      TUNEL method, with a immunohistochemical method, and with routine staining
      procedures, respectively. RESULTS: There were significant differences in the
      values of mean creatinine clearance between group 1 and group 3 and between group
      2 and group 3 (P < .05 for each comparison), but not between group 1 and group 2
      (P > .05). MDA levels in group 1 were high compared with the control group (P <
      .05) with a trend toward elevation relative to group 2 but the results were not
      statistically significant (P > .05). Renal tubular vacuolization in group 1 and
      group 2 animal were greater than in the control group, but no significant
      difference were observed between any of the groups (P > .05). Mononuclear cell
      infiltration in group 1 and group 2 hosts were higher than the control group, but
      there was no significant differences between the groups (P > .05). Afferent
      arteriolar hyalinization was observed group 1 and 2 but not group 3. There was a
      statistically significant difference between group 1 and group 3 and between
      group 2 and group 3 (P < .05 for each comparison). The expression level of TGF
      beta was higher in group 1 than group 2 or group 3 (P <.05 for each comparison)
      but group 2 and group 3 were similar (P > .05). Apoptotic cell death count of
      group 1 was higher than that in group 2 or group 3 (P < .05, for each
      comparison); moreover, group 2 also showed greater numbers of apoptotic cells
      than group 3 (P < .001). At the end of the 4 weeks, there was no intersititial
      fibrosis in any of the hosts. CONCLUSION: While cyclosporine caused increased TGF
      beta expression and apoptotic cell death in the renal tissue of rats colchicine
      prevented the increase in MDA serum levels, TGF-beta expression, and apoptosis in
      renal tissue. Our study suggests that colchicine may diminish the cyclosporine
      nephrotoxicity by its suppressing the expression of TGF-beta, apoptotic cell
      death, and MDA production.

PMID- 15251336
TI  - "Very delayed" graft function in a patient after living related kidney
      transplantation: a case report.
AB  - We report the case of a patient who experienced anuric renal transplant failure
      for 44 days after living related kidney transplantation. Immunosuppressive and
      other therapies were carefully adapted to the findings of frequent renal
      transplant biopsies, which ultimately led to excellent graft function.

PMID- 15251337
TI  - Is there a relation between duration of cyclosporine usage and right and left
      ventricular function in renal transplant patients? Tissue Doppler
      Echocardiography study.
AB  - BACKGROUND: Our aim was to investigate the effect of cyclosporine (CsA), which is
      commonly used in renal transplant patients and causes myocardial fibrosis and
      elevated arterial tension, on cardiac function. METHODS: Sixty-six renal
      transplant patients (RTPs) and 25 healthy controls were included in the study.
      Renal transplantation patients were divided according to time of CsA exposure:
      group 1 (0 to 36 months); group 2 (36 to 72 months) and group 3 (> 72 months).
      Systolic peak velocity (Sm, mitral; St, tricuspid) and mitral early (e)/late (a)
      (Me/a) and tricuspid e/a (Te/a) waves of the right and the left ventricles were
      measured by pulse-wave (PW) Doppler used for tissue Doppler imaging of both
      ventricles as well as the ventricle free wall near to the lateral tricuspid and
      the posterior mitral leaflets. The measurements included conventional diastolic
      early (E) and late (A) waves and deceleration time (DT) of the E wave,
      isovolumetric relaxation time (IVRT) of both ventricles, as well as left
      ventricular systolic ejection fraction (EF). RESULTS: There were no statistically
      significant differences between the groups with regard to demographic, clinical,
      and most biochemical characteristics. Left ventricular EF was normal in all
      groups; there were no statistically significant differences. IVRT and DT of left
      ventricle and right ventricle DT values were similar among RTPs. On the other
      hand, values were found to be increased in RTP groups compared with the control
      group. E/A ratio, Me/a Te/a of both ventricles were similar among RTPs. However,
      these values were found to be decreased in RTP groups compared with the control
      group. CONCLUSIONS: Although left ventricular systolic functions were normal in
      all groups, there were statistically significant impairments of biventricular
      diastolic function parameters among renal transplant recipients compared with the
      control group.

PMID- 15251338
TI  - Paraoxonase 192 polymorphism and its relationship to serum lipids in Turkish
      renal transplant recipients.
AB  - BACKGROUND: Cardiovascular disorders are the leading cause of death in patients
      with chronic renal insufficiency. Paraoxonase (PON1) gene variants have been
      identified as risk factors for cardiovascular disease (CVD). METHODS: We
      investigated the effect of PON1 192 polymorphisms on serum lipid profiles in 29
      renal transplant recipients and 26 control subjects. Distribution of the PON1 192
      gene polymorphism was determined by polymerase chain reaction-based restriction
      fragment length polymorphism. Serum lipid levels were measured enzymatically.
      RESULTS: Frequencies of PON1 192 AA, BB, and AB genotypes among the renal
      transplant recipients were 38.5%, 26.9%, and 34.6%, and among control subjects
      they were 35.75%, 17.9%, 46.4%, respectively. The genotype distribution for the
      PON1 192 polymorphism was not different between the two groups (P = NS, chi
      square test). The PON1 192 polymorphisms failed to consistently influence the
      serum lipid profiles in renal transplant recipients. CONCLUSION: We have shown
      that the 192 polymorphism of the PON1 gene is not associated with increased
      cardiovascular risk in renal transplant recipients.

PMID- 15251339
TI  - Predictors of cardiovascular events and associated mortality within two years of
      kidney transplantation.
AB  - BACKGROUND: Cardiovascular disease is the most common cause of death after renal
      transplantation. Furthermore, acute coronary syndrome (ACS) attributable to
      coronary artery disease (CAD) accounts for the majority of deaths due to
      cardiovascular disease posttransplant. While renal transplantation is the
      treatment of choice for end-stage renal disease, understanding the causes of
      graft and patient loss is exceedingly important to improve outcomes. METHODS:
      This observational case-controlled study included 780 patients who underwent a
      kidney transplant between 1989 and 2001 who experienced early ACS (within 2
      years). Patients were compared with controls matched for gender, year of
      transplant, and age. The primary outcome was the occurrence of an ACS event
      within 2 years after renal transplantation. RESULTS: Cardiovascular disease was
      the most common cause of death, with all 13 cardiovascular deaths due to CAD. An
      additional 15 episodes of nonfatal ACS episodes occurred. Thirty-seven percent of
      early ACS occurred perioperatively, the majority in the first 3 posttransplant
      months. On multivariate analysis, diabetes (OR [odds ratio] 5.56; P = .0007),
      smoking (OR 3.56; P = .034), and prior transplant (OR 2.81; P = .047) were
      associated with early ACS. CONCLUSIONS: Diabetes, smoking, and prior transplant
      were significantly associated with early ACS. The majority of events occurred
      perioperatively or within 3 months of transplant, highlighting the importance of
      improved screening and perioperative management.

PMID- 15251340
TI  - Arterial anastomosis disrupton in two kidney recipients of contaminated grafts
      from a donor with Gorham's syndrome.
AB  - Transmission of donor infections to immunosuppressed recipients may produce
      serious complications. Here, we report two cases of ruptured renal artery
      pseudoaneurysm within a few months after renal transplantation from a donor with
      Gorham's syndrome, a rare disease characterized by proliferation of vascular and
      lymphatic channels associated with extensive bony destruction. The donor had died
      of respiratory failure, sepsis, and anoxic brain death due to difficult airway
      control secondary to a maxillofacial deformity.

PMID- 15251341
TI  - A long-forgotten indwelling ureteral stent in a renal transplant patient.
AB  - Ureteral stents have proved to be an invaluable tool in the armamentarium of the
      urological surgeon. Stents have also been advocated as an adjunct for ureteral
      reconstruction in renal transplantation. However, stents can cause significant
      problems, including migration, fragmentation, and incrustation. More
      interestingly, it may possibly be forgotten. We herein report a case of a long
      forgotten indwelling ureteral stent for 7 years in a renal transplant patient.

PMID- 15251342
TI  - Prolonged ureteral stenting in obstruction after renal transplantation: long-term
      results.
AB  - BACKGROUND: Renal transplantation is an effective treatment for end-stage renal
      disease. Ureteral stenosis is the most frequent urologic complication. We report
      our long-term follow-up results concerning endourologic treatment of ureteral
      obstruction after renal transplantation. METHODS: Between May 1997 and September
      2000, 15 patients with renal transplant obstructive uropathy were managed with
      percutaneous nephrostomy and prolonged ureteral stenting. RESULTS: Percutaneous
      nephrostomies were performed successfully in all 15 kidneys. In 13 patients,
      antegrade ureteral stenting was attempted, which was successful in 11 patients
      (85%). After prolonged ureteral stenting (mean duration 15 months), the stent was
      removed in all patients, 90% of whom had no recurrence. During follow-up (36 to
      71 months; mean 51), urea, creatinine, sodium, and potassium determinations and
      ultrasound scans were performed. Success was defined as a reduction in
      hydronephrosis. No major complications were observed. CONCLUSIONS: Modern
      endourologic procedures have replaced open reconstructive surgery in most
      patients with ureteral obstruction after renal transplantation, because they may
      offer a definitive treatment with low morbidity.

PMID- 15251343
TI  - Sliding hernia containing the ureter--a rare cause of graft
      hydroureteronephrosis: a case report.
AB  - Obstructive uropathy following renal transplantation is frequently reported.
      However, ureteral obstruction due to its incorporation in a sliding hernia is a
      rare event. Herein, we report a case of late graft hydroureteronephrosis
      secondary to a sliding hernia containing the transplanted ureter. The diagnosis
      was confirmed with the aid of magnetic resonance urography and antegrade
      urography. Following hernioplasty, a decrease of serum creatinine level was
      achieved with significant decompression of the system.

PMID- 15251344
TI  - Fertility and contraceptive issues after kidney transplantation in women.
AB  - PURPOSE: Our purpose was to investigate reproductive performance among kidney
      transplant recipients. MATERIALS AND METHODS: We studied 126 kidney transplanted
      women 15 to 68 years of age including 33 who were single and 93 who were married.
      RESULTS: Infertility was seen in 10.4% of those who desired pregnancy, a rate
      similar to the general population. The most common method of contraception was
      coitus interruptus (56%), 22% of patients had tubal ligation, 6% had husbands who
      had vasectomies, 14% were using condoms, and only 2% used oral contraceptives.
      Among 33 pregnancies, 16 were unintended (48.5%). Most of the patients with
      unwanted pregnancy were using coitus interruptus (93.7%). In the group with
      unintended pregnancy, abortion was induced in three, spontaneous abortion or
      intrauterine fetal death occurred in six, and only seven pregnancies resulted in
      a live birth (43.7%). CONCLUSION: Kidney transplantation greatly improves
      fertility, so those who do not desire pregnancy should be protected by an
      effective method of contraception.

PMID- 15251345
TI  - Diabetic ketoacidosis following development of de novo diabetes in renal
      transplant recipient associated with tacrolimus.
AB  - Although drugs used in renal transplant recipients such as steroids,
      cyclosporine, and particularly, tacrolimus have diabetogenic potential, diabetic
      ketoacidosis is uncommon. There are few data concerning the long-term follow-up
      of these patients. Diabetic ketoacidosis occurred in a renal transplant recipient
      following de novo development associated with tacrolimus.

PMID- 15251346
TI  - Metastatic melanoma within a transplanted kidney: a case report.
AB  - A 57-year-old woman recipient of a cadaveric renal allograft displayed metastatic
      melanoma within the transplant. The patient, who received imunnosuppressive
      therapy with cyclosporine, azathioprine, and prednisone, displayed normal renal
      function for 10 months posttransplantation. She was admitted due to multiple,
      large, rapidly growing skin nodules over the lower abdomen and to dyspnea. After
      a diagnostic evaluation, the renal graft was removed, revealing metastatic
      melanoma within the transplanted kidney and 2 focal points of melanoma within the
      skin lesions. The patient returned to hemodialysis, received chemotherapy and
      interferon A, but failed to respond and died 11 days after the nephrectomy.

PMID- 15251347
TI  - Polyomavirus BK infection in Greek renal transplant recipients.
AB  - BK polyoma virus associated nephropathy is increasingly recognized as an
      important cause of allograft dysfunction among renal transplant recipients.
      Herein we present the cases of two renal transplant recipients who developed
      progressive functional deterioration suspicious for BK polyoma virus involvement.
      One patient had been treated with mycophenolate mofetil (MMF), cyclosporine
      (CsA), and prednisolone (P), and the second patient with tacrolimus (Tac), MMF,
      and (P). Using quantitative real-time polymerase chain reactions for BK virus
      DNA, we monitored the content of BK virus in the blood to evaluate disease
      progression. The high BK virus load initially detected in the blood samples from
      these patients decreased in the patient who received MMF, CsA, and P after the
      reduction of immunosuppression, but not in the patient who was treated with Tac,
      MMF and P. In contrast to previous reports, our patients had not received
      treatment with anti-lymphocyte globulin (ALG) or monoclonal anti-CD3 antibody
      (OKT3) after transplantation. It is concluded that even in the absence of
      vigorous antirejection treatment, immunosuppressive therapy based on Tac and MMF
      may carry the risk of BK virus-associated nephropathy. Because BK virus specific
      antiviral therapy is not available, its course may be monitored by measuring the
      viral load in blood.

PMID- 15251348
TI  - Septic arthritis caused by Nocardia asteroides in a renal transplant recipient.
AB  - Although articular complications are common following renal transplantation,
      septic arthritis is not frequent. Previous bacterial infection in an another site
      is a consistent finding and the knee is the most often affected joint. We present
      a 30-year-old female renal transplant recipient with recurrent pulmonary
      infiltrates preceding septic arthritis of her left knee. Cultures of the
      aspirated synovial fluid yielded a gram-positive, rod-shaped bacterium later
      identified as Nocardia asteroides. The patient was treated with oral trimethoprim
      sulfamethoxazole without any side effect. Nocardia is a rare but serious cause of
      infection in renal transplant recipients but there is no well-known predisposing
      factor. Recently mycophenolate mofetil has been implicated as a factor associated
      with Nocardia infections. Prolonged courses of treatment with sulphonamides are
      recommended.

PMID- 15251349
TI  - Cross-sectional assessment of psychiatric disorders in renal transplantation
      patients in Turkey: a preliminary study.
AB  - BACKGROUND: Psychiatric disorders such as depression and anxiety may be seen
      after a successful renal transplantation (RTx). The aim of this cross-sectional
      study was the assessment of psychiatric disorders after RTx in Turkey. The value
      of self-report scales in predicting depression and anxiety was also assessed.
      PATIENTS AND METHODS: The study group consisted of 20 male and 20 female RTx
      patients (mean age 35.42 +/- 10.09 years), with a mean duration of 61.65 +/-
      48.30 months of follow-up after transplantation. All patients were assessed with
      the validated Turkish versions of Structured Clinical Interview for the DSM-IV
      (SCID-I), Beck Depression Inventory (BDI), Hospital Anxiety Depression Scales
      (HADS), Spielberger Trait Anxiety Inventory (STAI-I), and Beck Hopelessness Scale
      (BHS). RESULTS: Twenty of the 40 patients warranted a DSM-IV psychiatric
      diagnosis with SCID-I evaluation. Major depression was observed in 25% of
      patients. The remaining diagnoses were within the affective and/or anxiety
      spectrum disorders. The set of age, gender, education, income, marital status,
      employment, type of transplantation, duration of illness, and duration after the
      transplantation was not significantly different between patients with or without
      psychiatric diagnoses. BDI, HADS, STAI-I, and BHS were significantly higher among
      patients with psychiatric diagnoses at P = .001 level using Student t test. Even
      after control of the variance explained by the set of demographic variables,
      hierarchical regression analysis revealed that HADS scores significantly
      predicted the psychiatric morbidity (P = .003). CONCLUSION: The frequency of
      psychiatric disorders is quite high in renal transplantation patients.
      Additionally, HADS, which significantly predicts depression and anxiety, may be
      used for screening purposes.

PMID- 15251350
TI  - Three patterns of voluntary consent in the case of adult-to-adult living related
      liver transplantation in Japan.
AB  - To elucidate the psychosocial aspects of the donors' decisions to engage in adult
      to-adult living related liver transplantation, we interviewed a total of five
      institutional ethics committee members who had experience with reassessing
      informed consent prior to surgery. Qualitative analysis revealed several nuances
      of voluntary consent consisting of three patterns: "unconditional consent" is
      consent from the bottom of one's heart to save a family member's life; "pressured
      consent" describes a donor who feels implicit pressure to donate despite fear;
      and "ulterior-motivated consent" defines a donor who has a hidden motive. This
      study diverges from previous work in that it employs a qualitative approach to
      deconstructing the psychosocial intricacies of the informed consent process in
      adult-to-adult LRLT. This initial study raises several questions on the meaning
      of voluntary informed consent in adult-to-adult living related liver
      transplantation.

PMID- 15251351
TI  - Accurate method for clinical assessment of right lobe liver weight in adult
      living-related liver transplant.
AB  - INTRODUCTION: Prior to transplantation of segmental liver grafts to adult
      recipients, it is crucial to confirm that the graft size is safe for the donor,
      yet adequate for the recipient's metabolic needs. Computed tomography (CT) and
      magnetic resonance imaging (MRI) are the current best standards. We applied a new
      formula to estimate right liver lobe weight in living donors and compared our
      results with CT and MRI. METHODS: Between August 1998 and December 20, 91 adults
      received right lobes from living donors. Donor liver volumes were assessed by CT
      or MRI. Actual weights of right lobe grafts were determined after back table
      flushing. We estimated whole liver weights using the formula: 772 x body surface
      area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole
      liver weight (R-57). RESULTS: Mean actual right lobe weight (n = 90) was 855.83
      +/- 183.4 g. Estimated right lobe weight was 858.08 +/- 90.80 (R-57, P = NS);
      1077.35 +/- 263.07 mL for CT (P = .0001), and 1185.07 +/- 350.10 mL for MRI (P =
      .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no
      significant difference with R-57 GRWR but there was a difference from CT and MRI
      GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR
      within 20% of the corresponding actual value were 80% and 90%, respectively, for
      R-57 versus 36% and 43% for the imaging studies (P = .0001). CONCLUSION: With
      readily available software to calculate BSA, physicians can predict right lobe
      weight knowing only the donor's height and weight. CT and MRI will only be
      necessary for anatomic liver mapping.

PMID- 15251352
TI  - Cadaveric renal transplantation in hepatitis B antigen-positive recipients using
      hepatitis B antigen-positive donor organs with lamivudine treatment.
AB  - Although renal transplantation has been regarded as the best renal replacement
      therapy in end-stage renal disease patients, there have never been enough organ
      donors. Therefore, hepatitis B surface antigen (HBsAg)-negative patients are
      often given priority over HBsAg-positive patients. We performed cadaveric renal
      transplantation in six HBsAg-positive recipients given HBsAg-positive donor
      organs who were on lamivudine treatment. Donors were found to have normal renal
      function by serum and urine laboratory tests. All recipients underwent liver
      biopsies before transplantation; those with liver cirrhosis were excluded. All
      recipients were treated with 100 mg lamivudine once daily because of positive
      titers of hepatitis B viral (HBV) DNA (three patients), and increased levels of
      alanine aminotransferase (ALT) (three patients). During the follow-up period, one
      patient died from hepatic failure at 50 months after transplantation without
      deterioration of graft function. The remaining five patients showed sustained
      normal ALT levels. Decreases in HBV DNA titer were observed among patients who
      were positive before transplantation, but did not reverse to negative. Acute
      rejection developed in two patients: one was treated successfully with steroid
      pulse therapy, and the other had two bouts of acute rejection within a 33-month
      interval. The first was successfully treated with steroid pulse therapy, but the
      second failed. The four remaining patients have maintained normal renal function
      for a considerable time. HBsAg-positive donor organs must be used carefully in
      renal transplantation of HBsAg-positive recipients.

PMID- 15251353
TI  - Massive hepatic artery atherosclerosis of an otherwise suitable donor liver: a
      case report.
AB  - Most of the few reports about hepatic artery disease found in the literature
      describe hepatic artery aneurysms or hepatic artery calcifications.
      Atherosclerosis of the hepatic artery is not commonly evaluated during deceased
      donor liver procurement. Herein we present a case of a stable 47-year-old
      Caucasian female donor whose liver function tests were within normal limits and a
      liver biopsy showed less than 5% steatosis. The liver when received at our center
      appeared grossly unremarkable. Back-table evaluation showed a complete occlusion
      of the trunk of the proper hepatic artery. The pathology report revealed hepatic
      occlusion due to arterial atherosclerosis. Transplantation was canceled, and the
      liver was used for isolated hepatocyte perfusion, revealing < 25% hepatocyte
      viability. Hepatic artery atherosclerosis and patency need to be evaluated at the
      time of procurement to prevent recipient morbidity due to anesthetic induction,
      or initiation of a recipient abdominal incision prior to declining the liver
      graft for this rare finding.

PMID- 15251354
TI  - Impact of pretransplant MELD score on posttransplant outcome in living donor
      liver transplantation.
AB  - It is not clear whether pretransplantation MELD (model for End-Stage Liver
      Disease) score can foresee posttransplant outcome. We retrospectively evaluated
      80 adult patients (55 men, 25 women) who underwent living donor liver
      transplantation between September 1998 and March 2003. Five other patients with
      fulminant hepatitis were excluded. The UNOS-modified MELD scores were calculated
      to stratify patients into three groups: group 1) MELD score less than 15 (n =
      13); group 2) MELD score 15 to 24 (n = 36); and group 3) MELD score 25 and higher
      (n = 26). The patients were predominantly men (n = 52, 69.3%) with overall mean
      age of 43.9 years (range, 17-62 years). The mean follow-up was 15.7 months
      (range, 1-47; median = 14 months). The mean MELD score was 22.7 (range, 9-50;
      median = 21). The overall 1- and 2-year patient survivals were 87% and 78.7%,
      respectively. The 1-year patient survivals for groups 1, 2, and 3 were 100%, 87%,
      and 79%; respectively. 2-year survivals, 100%, 79%, and 61%, respectively.
      Survivals stratified by MELD showed no statistically remarkable differences in 1
      year and 2-year patient survival (P = .08). In contrast, 1-year and 2-year
      patient survival rates for UNOS status 2A, 2B, and 3 were 73%-50%, 95%-91%, and
      91%-91%, statistically significant difference (P = .002). Finally, to date
      preoperative MELD score showed no significant impact on 1- and 2-year
      posttransplant outcomes in adult-to-adult living donor liver transplantation
      recipients, but we await longer-term follow-up with greater numbers of patients.

PMID- 15251355
TI  - Liver transplant for the septuagenarians: importance of patient selection.
AB  - With the increasing success of liver transplantation (OLT), more patients above
      70 years of age are being considered for OLT. There is not enough data about the
      predictors for survival in this patient population. We retrospectively analyzed
      the medical records of 33 patients at least 70 years of age who received 34 OLT
      from July 1995 to July 2002. There were 16 women and 17 men of mean age 73.7
      years. Etiologies of end-stage liver disease (ESLD) were: HCV (17/33, 52%),
      cryptogenic cirrhosis (8/33, 24%), PBC (3/33, 9%), Laennec's cirrhosis (2/33,
      6%), and others (3/33, 9%). According to the UNOS classification, 15/34 (44%)
      were status 3, 16/34 (47%) status 2, and 3/34 (9%) status 1. Among 13/33 patients
      who died (39%), 1-year and 3-year survival rates were 78.79% and 71.43%,
      respectively. Based on UNOS criteria, 4/15 (26%) were status 3; 6/16 (37%),
      status 2; and 3/3 (100%), status 1 (P value = .04 for status 1 patients). There
      was no statistical differences between the scores using the Model for End-Stage
      Liver Disease (MELD) among those who died (MELD (19) versus MELD (17.35)
      respectively (P = .50). There was a statistically significant difference in cold
      ischemia time (CIT) and warm ischemia time (WIT) between those who died (P = .024
      and.010, respectively). These results suggest that in this group of patients UNOS
      status classification, CIT and WIT correlate with survival. The sample size was
      too small to derive a conclusion about the association with the MELD score.

PMID- 15251356
TI  - Should patients with chronic hepatitis C infection be transplanted?
AB  - Chronic hepatitis C (HCV) infection affects more than 170 million people
      throughout the world and 2 to 3 million Americans. End-stage liver disease
      secondary to chronic HCV infection is the most frequent indication for liver
      transplantation in this country. Currently, the gold standard for treatment for
      immunocompetent patients is a combination of peginterferon (PEG-IFN) and
      ribavirin for 6 to 12 months depending on the genotype. This treatment achieves a
      sustained virological response (SVR) in 54% to 61% of patients overall. Almost
      50% of patients do not respond or have recurrences posttreatment and progress in
      over 10 to 20 years into chronic liver disease and its complications. Liver
      transplantation is the only therapeutic modality that impacts on quality of life
      and survival of these patients. However, recurrence of HCV in the new allograft
      is universal with accelerated progression to cirrhosis in 5 to 10 years. Response
      to treatment is usually low (20% to 30%), and associated with significant side
      effects and depression. A significant percentage of patients with recurrent HCV
      after transplantation require retransplantation to control the complications of
      end-stage liver disease. Other solid organ transplants recipients already HCV
      positive, or infected at the time of transplantation from blood transfusions or
      an infected graft, develop accelerated, progressive liver disease facilitated by
      the adverse effects of immunosuppression in addition to HCV replication. To
      prevent morbidity, mortality, and high costs related to the consequences of HCV
      infection, all solid organ transplant candidates should be tested for HCV
      infection and treated appropriately with PEG-IFN and ribavirin prior to
      transplantation.

PMID- 15251357
TI  - Remaining caudate lobe in the right lobe graft in living donor liver
      transplantation: a blind spot?
AB  - The right margin of the caudate lobe is obscure. Therefore, a part of the caudate
      lobe (a part of the right side of the paracaval portion) seems almost always to
      remain with the right lobe graft during the standard harvesting procedure. We
      reviewed the intraoperative findings and the postoperative courses of donors and
      recipients of 11 consecutive living donor liver transplantations using right lobe
      grafts. Further, we used computed tomography during the postoperative course to
      investigate whether the remaining caudate lobe was present in the right lobe
      graft and whether it produced serious complications. Four recipients displayed an
      intraoperative bile leak from a remaining part of the caudate lobe after the
      completion of biliary reconstruction. With the exception of one case who
      developed repeated bile leakage from the same origin which eventually healed
      during a long-term postoperative course, Most recipients showed no postoperative
      biliary complications. Although a remaining caudate lobe was detected on
      postoperative computed tomography in all recipients, it produced no serious
      complications. In conclusion, a part of the right side of the paracaval portion
      of the caudate lobe almost always remains with a right lobe graft during the
      standard harvesting procedure. However, the implications of this phenomenon seem
      to be benign.

PMID- 15251358
TI  - Intraoperative assessment of hepatic venous congestion with direct clamping of
      the hepatic vein trunk for living donor liver transplantation.
AB  - We devised a hepatic vein clamping method to assess the amount of hepatic venous
      congestion (HVC) before liver transection. From February 2003 to May 2003, this
      method was applied to 5 of 58 living donor livers especially to assess donor
      safety. The left portal vein and proper hepatic artery as well as the middle
      hepatic vein (MHV)-left hepatic vein (LHV) trunk were clamped simultaneously to
      assess the HVC in the remnant right lobe before performing extended left
      lobectomy. As three donors demonstrated the extent of the HVC equivalent to about
      40% of the right lobe volume (RLV), their operations proceeded according to the
      preoperative plan. The territory of HVC after liver transection was the same as
      that observed with direct clamping of the hepatic vein. However, one donor showed
      massive HVC more than 50% of RLV and the operative plan was adjusted to harvest
      only the left lobe without the MHV trunk for donor safety. To assess the HVC in
      the remnant left lobe, the isolated LHV trunk was occluded after clamping the
      donor's proper hepatic artery. The whole left lobe except for a small area at the
      anterior portion of the medial segment became discolored on LHV clamping: the
      opposite demarcation appeared on MHV clamping. The amount of HVC was so small
      that we harvested the right lobe with the MHV trunk. All donors and recipients
      recovered uneventfully. We believe that this direct clamping method makes the
      assessment of HVC feasible before parenchymal transection of a donor liver.

PMID- 15251359
TI  - Intraoperative fluid management of living donor versus cadaveric liver transplant
      recipients.
AB  - Living donor liver transplantation has increasingly become an alternative to
      cadaveric donor liver transplants for select adult patients. Because these cases
      can be performed electively, living donor recipients may have better compensated
      liver disease at the time of surgery than cadaver donor recipients. However, it
      is unknown if this difference would have a significant effect on their
      intraoperative course. Therefore, we compared the intraoperative fluid management
      of patients receiving liver grafts from either living or cadaveric donors (n =
      25, each group). Patient groups did not differ in demographics or baseline
      laboratory values. The duration of anesthesia and anhepatic phases were
      significantly longer in living donor cases (651 +/- 80 minutes vs 409 +/- 20 and
      55 +/- 14 vs 45 +/- 6, P < .05). Adjusted for anesthesia time and patient weight,
      fluid administration (crystalloid and albumin) was not different between the two
      groups. Intraoperative transfusion requirements were also not significantly
      different in recipients from living donors versus cadaveric donors with regard to
      red blood cells, fresh frozen plasma, platelets, and cryoprecipitate. However,
      arterial oxygenation was better preserved in recipients from living donors. The
      PaO2/FiO2 (P/F) ratio at the end of the procedure was significantly better in
      patients receiving livers from living rather than from cadaveric donors (P/F
      ratio 335 +/- 114 mm Hg vs 271 +/- 174, P < .05). Our results indicate that while
      intraoperative fluid and transfusion requirements are similar, the impact of
      transplantation on pulmonary gas exchange is more pronounced in patients
      receiving organs from cadaveric donors. This difference may arise from longer
      cold ischemia times present in the cadaveric donor group.

PMID- 15251360
TI  - Perioperative kinetics of heat shock protein 60 in serum during orthotopic liver
      transplantation.
AB  - INTRODUCTION: Heat shock proteins (HSP) play essential roles in the synthesis,
      transport, and folding of proteins. During ischemia/reperfusion (I/R) injury to
      orthotopic liver transplants (OLT), disassembly of oligomeric complexes and
      unfolding of proteins are likely to occur, producing a major burden on HSP to
      prevent and/or reverse these events. To date, all studies have evaluated HSP
      expression in tissues after an I/R injury. No data are available on HSP serum
      levels during I/R injury in liver graft recipients. PATIENTS AND METHODS: We
      evaluated the intraoperative and perioperative kinetics of HSP60 in the serum of
      25 liver graft recipients. RESULTS: We observed a significant increase in serum
      levels of HSP60 at 4 hours compared with 30 minutes after reperfusion of the
      graft (P = .028). The perioperative HSP60 kinetics in serum neither correlated
      with the cold ischemia time nor the indocyanin green clearance. The type of
      preservation solution had no effect on serum HSP60 levels. CONCLUSION: This first
      study provides evidence for increased serum levels of HSP60 after reperfusion in
      OLT. The perioperative kinetics of HSP60 in serum may result from suppressed
      protein synthesis caused by a reduced energy charge of hepatocytes during early
      reperfusion, impaired transcription, and/or corticosteroid treatment. Further
      studies are needed to clarify the role of HSP60 under clinical conditions
      including immunosuppressive medications in human OLT.

PMID- 15251361
TI  - Modifications of cerebral vascular resistance and autoregulation after graft
      reperfusion during human orthotopic liver transplantation.
AB  - We have studied cerebral blood flow velocity (CBFV) and cerebral autoregulation
      (CA) in 23 orthotopic liver transplantation (OLT) patients using transcranial
      doppler. CBFV was continuously recorded using a fixed (helmet) 2-Mz probe through
      the trans-temporal window. CA changes were studied using a linear regression
      analysis of percentile changes in CBFV and mean arterial blood pressure (MABP)
      after phenylephrine infusion compared with baseline. Pearson's "r" coefficient
      was considered an index of CA. In case of autoregulation is lost "r" tends to 1,
      thus representing complete dependence of CBFV on MABP. We regarded the slope
      coefficient parameter "S" as an index of cerebral vascular resistance (CVR),
      namely, the ratio of the corresponding variations of CBFV to MABP. Wilcoxon test
      showed a significant increase in both "r" and "S" between the anhepatic versus
      postreperfusion phases (within the first hour) and versus recovery in the
      neohepatic phase (end of surgery). A decreased CVR was observed within the first
      hour after graft reperfusion producing a loss of CA. These phenomena lead to an
      increase of CBFV and exposed the brain to hyperperfusion.

PMID- 15251362
TI  - Beneficial effect of liver transplantation on bone mineral density in small
      infants with cholestasis.
AB  - Reports of bone mineral density in children after liver transplantation are few.
      Eleven cholestatic children were analyzed before and 6 months after liver
      transplantation. No changes in serum levels of calcium, alkaline phosphates, or
      25OHD were observed before versus after LTx. The serum levels of phosphorus and 1
      25(OH)2D3 as well as total bone mass density and Cole index were significantly
      increased after liver transplantation.

PMID- 15251363
TI  - Living donor liver transplantation for end-stage hepatitis C.
AB  - Living donor liver transplantation is important for patients with end-stage viral
      hepatitis because of the shortage of organs from deceased donors. However,
      preliminary results indicate that living liver donation might be disadvantageous
      for hepatitis C virus-positive patients. Twenty-seven patients who underwent
      living donor liver transplantation for hepatitis C virus cirrhosis preemptively
      received antiviral therapy using interferon-alpha2b and ribavirin, which was
      started an average of 32 days after the operation and continued for at least 6
      months thereafter. The serum hepatitis C virus RNA became negative in the 8 of 16
      patients with more than 1 year follow-up. The cumulative 3-year patient survival
      was 85%, which was comparable to that of hepatitis C virus negative patients (n =
      93; 90%). Preemptive antiviral therapy after transplantation may be necessary for
      satisfactory results after living donor liver transplantation.

PMID- 15251364
TI  - Simultaneous liver-kidney transplantation for glycogen storage disease type IA
      (von Gierke's disease).
AB  - INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency
      of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although
      significant progress has been achieved in the management of patients with GSDIa,
      complications still emerge. The potential for development of liver adenomatosis
      and kidney failure makes these patients candidates for simultaneous liver-kidney
      transplantation (SLKT). Herein, we describe such a transplantation in a patient
      affected by this rare storage disease. METHODS: A 25-year-old female patient with
      GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The
      patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was
      8 hours without hemotransfusion. Only a transitory lactic acidosis was observed.
      Laboratory results normalized on postoperative day 7. The patient was discharged
      on postoperative day 9. After 4 months, the patient is in good condition with
      well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage
      renal disease secondary to GSDIa should be considered for SLKT, especially when
      the disease is in an early stage.

PMID- 15251365
TI  - Lower liver transplant success in females: gender differences in metabolic
      response to global ischemia.
AB  - BACKGROUND: Research has shown that gender plays a significant role in the
      metabolic processes of different organs and that transplanting livers of females
      into male or female recipients has significantly higher failure rates. To
      understand why, this study examined whether gender differences exist in various
      metabolic responses of livers to ischemia. METHODS: The following metabolic liver
      parameters in Sprague-Dawley rats (male, n = 14; and female, n = 18) were
      examined; adenosine triphosphate (ATP) and lactate expressed as micromoles/g dry
      weight, and hydrogen ion content [H+] expressed as 10(-8) mol/L. In vivo liver
      biopsy specimens were compared with ischemic biopsy specimens at 3, 10, 15, 30,
      and 45 minutes (37 degrees C). RESULTS: In vivo female ATP values (9.9 +/- 0.8)
      were similar to males (9.8 +/- 0.9) and both had early, rapid decline during
      ischemia reaching 20% of baseline by 10 minutes of ischemia. In contrast, male
      liver lactate accumulation peaked by 3 minutes and at much lower levels (35 +/-
      13), whereas female liver lactate peaked by 10 minutes at 71 +/- 11. For the rest
      of the ischemic period, female livers exhibited significantly (P < .05) greater
      lactate accumulation. Female liver H+ levels also increased to higher levels (55
      +/- 10) than the male livers (37 +/- 7) and this pattern was significantly (P <
      .05) different from 10 minutes onward. CONCLUSIONS: Although livers of females
      ultimately have similar ATP profiles to livers of males, they experienced more
      rapid and greater degree of tissue lactate and H+ accumulation during ischemia.
      Therefore, female livers have increased acidosis during ischemia, which could
      adversely affect transplant outcome.

PMID- 15251366
TI  - Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant
      recipients with recurrent HCV infection: preliminary results of an open
      prospective study.
AB  - Allograft reinfection with hepatitis C virus (HCV) in transplant recipients
      occurs commonly and represents a major concern in the transplant setting.
      Suppression of viral replication in HCV transplant patients should prevent or
      delay progression to cirrhosis and graft failure. In this ongoing study, we
      present preliminary data from a prospective trial of standard interferon (IFN)
      alpha-2b (2 million units daily) for 3 months and subsequent peginterferon (PEG
      IFN) alpha-2b (1.5 microg/kg/week) for 9 months. IFN therapy was combined with
      ribavirin (10 to 12 mg/kg). So far, HCV has become undetectable by qualitative
      PCR in 33% of patients while 25% had a reduction of HCV RNA to undetectable by
      the bDNA assay and 42% had no virological response after 6 months of therapy. A
      biochemical response was detected in 42% of patients. Improvement of inflammatory
      activity was observed in 42% of patients after 6 months. In three patients anemia
      necessitated administration of erythropoietin and three patients received
      granulocyte-colony stimulating factor (G-CSF) due to leucopenia [corrected] In
      conclusion, we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b
      therapy in combination with ribavirin provides biochemical and virological
      benefits in transplant recipients with established recurrent HCV infection.

PMID- 15251367
TI  - Rituximab therapy for life-threatining immune hemolytic anemia in a liver
      tranplant recipient: a case report.
AB  - Rituximab an anti-CD20 chimeric monoclonal antibody directed against the CD20
      antigen on B lymphocytes, has been demonstrated to be highly effective for B-cell
      depletion. Because of its biological properties, it has become as a treatment
      option for a variety of autoimmune diseases. We report successful treatment of a
      25-year-old male cadaveric liver retransplant recipient who displayed severe
      immune hemolytic anemia with rituximab, despite no previous response to
      corticosteroids plus intravenous immune globulin therapy.

PMID- 15251368
TI  - De novo cryptogenic hepatitis after sustained eradication of hepatitis C
      following liver transplantation.
AB  - Patients with recurrent hepatitis C (HCV) after liver transplantation (OLT) are
      often treated with interferon and ribavirin in an attempt to eradicate HCV and
      prevent cirrhosis. We report four patients who developed de novo cryptogenic
      hepatitis following sustained eradication of recurrent HCV, which led to
      decompensated liver disease in two patients, both of whom required listing for
      retransplantation. Between September 2000 and October 2001, 38 consecutive
      patients with recurrent HCV were treated with interferon alpha 2b and ribavirin,
      of whom eight patients (21%) developed a sustained response to HCV eradication.
      Four of these patients developed cryptogenic hepatitis, which led to
      decompensated cirrhosis in two patients. Both patients were listed for
      retransplantation but died on the waiting list. No etiology for liver disease was
      identified despite extensive investigations in all four patients including
      postmortem analysis in the two patients. We hypothesize that these individuals
      developed an aberrant immune response leading to allograft injury whose severity
      may be determined by underlying haplotype, degree of immunosuppression,
      presence/absence of HCV, and duration of treatment. We have not found any similar
      reports in the literature but anticipate more cases to be reported given the
      universal use of antiviral therapy for recurrent HCV.

PMID- 15251369
TI  - T-helper and T-cytotoxic cell subsets monitoring during active cytomegalovirus
      infection in liver transplantation.
AB  - OBJECTIVE: The objectives of this study was to analyze the peripheral blood T
      lymphocyte subsets of the Th1-related versus Th2-related cytokines of CD4+ cells,
      and the Tc1 versus Tc2 cytokines of CD8+ cells liver transplant recipients with
      versus without active cytomegalovirus (CMV) infection. METHODS: Isolated
      peripheral blood mononuclear cells (PBMC) were stimulated using
      PMA/Ionomycin/Monensin. Interleukin (IL)-4 and interferon gamma (IFN-gamma)
      production by CD4+ and CD8+T cells were determined using fluorescence-activated
      cell sorter (FACS) analysis. RESULTS: The ratios of CD4/CD8 were significantly
      lower among active CMV-infected patients. The levels of Th2 and Tc2 cytokines (IL
      4) were similar between CMV-infected and uninfected patients. However, the levels
      of Th1-type and Tc1-type cytokines (IFN-r) were significantly lower among active
      CMV-infected patients. CONCLUSIONS: Low levels of Th1-type cytokines seem to
      correlate with active CMV infection in liver transplant recipients.

PMID- 15251370
TI  - Prevalence of previous hepatitis A virus infection in renal transplant patients
      with hepatitis C: evidence of persistent anti-hepatitis A virus immune response.
AB  - Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney
      transplant recipients are scarce. There is little information concerning natural
      immunity acquired after acute HAV infection. In most renal transplant recipients,
      anti-HAV antibodies are not detectable after vaccination; it is reasonable to
      suppose that immunosuppressive therapy interferes with the immunity. The
      objective of this study was to evaluate, in an endemic area, the prevalence of
      anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic
      hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in
      40 HCV-positive renal transplant recipients. This group showed a 90% prevalence
      of previous HAV infection. These findings suggest that in an endemic area, the
      prevalence of previous HAV infection is high, even among immunosuppressed
      patients. HAV antibodies acquired after natural infection are detectable even
      after the onset of immunosuppressive therapy. These data should be considered
      when renal transplant recipients are considered for HAV vaccination.
      Prevaccination screening of renal transplant recipients must follow the same
      guidelines as those for immunocompetent subjects.

PMID- 15251371
TI  - Deferred versus prophylactic therapy with gancyclovir for cytomegalovirus in
      allograft liver transplantation.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of deferred versus
      prophylactic therapy with gancyclovir to prevent cytomegalovirus (CMV) infection
      or disease in liver transplantation recipients, and to alter the timing of
      infection or the incidences of acute rejection, chronic rejection, or death.
      METHODS: We retrospectively studied 89 consecutive liver transplant recipients
      with a minimum of 1 year follow-up. CMV early antigen detection (pp65) was
      performed weekly for the first 2 months and thereafter monthly for an additional
      10 months. Forty-one recipients were administered prophylactic treatment and (48
      recipients) deferred therapy for positive antigenemia. RESULTS: During the first
      year after transplantation, CMV infection or disease developed in 61% or 12.2% of
      those treated with prophylactic therapy and 54.1% or 31.3% of those treated with
      deferred therapy (P = 0.51 or P = 0.032, respectively). The mean time to CMV
      disease in the prophylactic group was 161 +/- 33 days compared with 82 +/- 27
      days for the deferred therapy arm (P < 0.001). Subgroup analysis based on CMV
      serological status also showed prophylactic treatment significantly diminished
      CMV disease in the CMV IgG antibody negative group. No patients died in the
      prophylactic group, and one died in the deferred group (P = 0.54). The incidence
      of acute rejection episodes was 34% in the prophylactic and 46% in the deferred
      group (P = 0.26). Chronic rejection was observed in two recipients in the
      prophylactic group versus one recipient in the deferred arm (P = 0.35).
      CONCLUSION: Compared with deferred therapy prophylactic therapy with gancyclovir
      decreased CMV disease and delayed the onset of CMV disease after liver
      transplantation.

PMID- 15251372
TI  - Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor
      liver transplant recipients.
AB  - OBJECTIVE: Plasma drug concentrations are generally considered to reflect
      efficacy and pharmacokinetics more directly than those in whole blood. However,
      whole blood has been selected as the matrix to monitor concentrations of
      tacrolimus (FK506), because it is difficult to accurately measure plasma FK506
      concentrations. Because FK506 highly and saturably binds in blood cells, a change
      in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we
      investigated effects of Hct on FK506 pharmacokinetics. METHODS: First, we
      analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we
      employed an equation, which describes saturable binding of FK506 to blood cells,
      and simulated plasma FK506 concentrations and clearances using the above equation
      with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages
      and whole blood FK506 concentrations to predict plasma FK506 concentrations in
      living donor transplant recipients. RESULTS: In the simulation study, the Hct
      changed plasma FK506 concentrations and clearances based in whole blood. In
      living donor liver transplant recipients, whole blood FK506 concentrations were
      maintained within a therapeutic range, while the Hct varied after
      transplantation. The correlation of Hct with the ratio of dose/trough
      concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker
      than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). CONCLUSION: Hct
      may be an important factor affecting the pharmacokinetics of FK506 in living
      donor liver transplantation recipients. It may be necessary to take Hct into
      consideration in the FK506 dosing regimen, especially when the Hct is low.

PMID- 15251373
TI  - Blood pressure profile and treatment quality in liver allograft recipients
      benefit of tacrolimus versus cyclosporine.
AB  - Organ transplant recipients display a high cardiovascular mortality rate. The
      type of immunosuppression has a major impact on cardiovascular risk factors
      (e.g., hypertension [HTN]). We assessed 24-hour blood pressure (BP) and metabolic
      profiles in a cohort of 106 long-term liver allograft recipients treated with
      either tacrolimus (Tac) or cyclosporine (CyA). The median age of patients was
      50.8 years (range, 11 to 77) and the median time of follow-up was 65.4 months
      (ranges 12 to 168). Immunosuppression included low-dose steroids and either Tac
      (n = 46) or CyA (n = 60). Twenty-four-hour BP measurements revealed a significant
      difference in systolic BP (127.1 mmHg [94 to 163] Tac versus 132.7 mmHg [103 to
      177] CyA; P <.03), and in mean arterial and diastolic blood pressures. In
      addition, the relative number of normotensive patients was significantly higher
      among Tac-treated patients (69.6% versus 34.8%). It is of note that the true
      incidence of HTN was higher after the number of patients with a pathological 24-h
      BP measurement was added to the initial number of patients already known to have
      HTN. No less than 76.4% of all long-term liver transplanted patients showed HTN.
      The results were unrelated to cumulative steroid dosage, frequency of
      antirejection therapy or underlying primary liver disease. In summary,
      immunosuppression-induced HTN is more common in CyA-treated than Tac-based
      regimens. Moreover, we found a substantial lack of detection of HTN in long-term
      liver transplant patients who received an insufficient quality of
      antihypertensive treatment. These findings have implications for the early
      diagnosis and treatment of HTN in liver transplant recipients.

PMID- 15251374
TI  - Outcome of simultaneous kidney pancreas transplantation: a single center
      analysis.
AB  - The aim of this study was to evaluate the outcome of simultaneous kidney pancreas
      transplantation (SKPT) by various surgical techniques. The 161 patients submitted
      to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to
      1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50
      whole pancreas with enteric diversion (40 with systemic and 10 with portal
      drainage) (from 1999 to September 2002). A positive effect on patient survival
      was evident using enteric diversion versus the duct occlusion group (P = .005),
      and versus the bladder diversion group (.035), and on pancreas graft survival in
      the enteric diversion versus the duct occlusion group (P < .028). These
      improvements may be due to refined donor and patient selection criteria, surgical
      technique, and immunosuppression.

PMID- 15251375
TI  - A prospective comparison of bladder versus enteric drainage in vascularized
      pancreas transplantation.
AB  - In previous years, the number of pancreas transplants has increased
      significantly. Debate continues over the optimum technique for exocrine drainage.
      Enteric drainage (ED) has recently been increasingly popular owing to the long
      term complications of bladder drainage (BD). We prospectively evaluated 40
      consecutive pancreas transplant recipients undergoing either bladder (n = 20) or
      enteric (n = 20) drainage. After simultaneous kidney-pancreas transplantation 1
      year patient, kidney, and pancreas graft survival rates were 95%, 95%, 85% for
      the BD group, and 90%, 85%, 85%, for the ED group. Surgical complications were
      not significantly different between the two groups. The incidence of acute
      rejection, major infections and cytomegalovirus disease were also similar. The
      length of the initial hospital stay was likewise comparable. However, the BD
      group was characterized by a slight increase in the number of urologic
      complications, metabolic acidosis, and dehydration. Our results suggest excellent
      patient and graft survival irrespective of the drainage technique.

PMID- 15251376
TI  - A modified automated method for isolation of viable pancreatic islets in
      laboratory animals.
AB  - To achieve successful islet transplantation, a high viability is required. For
      this reason an automated method including two chambers: one for islets isolation
      and one for recirculation and collection was developed. Recently, we produced a
      modified version of this work by building a similar system of glass where marbles
      were not used for disaggregation, and the pancreatic tissue had to be disrupted
      mechanically before the digestion phase. By using the reconfigured system, we
      obtained 260 +/- 20 islets from each Wistar albino rat (weighing 220 to 240 g)
      pancreas. Islets were observed at 35 minutes after the start of perfusion (closed
      circuit) and the optimum time to stop the isolation determined to be 40 minutes
      based upon islets viability. Although the present system is configured for islet
      isolation from small laboratory animals (rat, mouse), we have also obtained
      thousands of islets at 25 minutes after treatment of a 0.5-g piece of pig
      pancreas. Compared to the time-consuming manual method usually used for islet
      isolation from small laboratory animals, the new technique is economic, easy to
      use, and does not reduce islets viability.

PMID- 15251377
TI  - The role of current product release criteria for identification of human islet
      preparations suitable for clinical transplantation.
AB  - BACKGROUND: Alloimmunity, autoimmunity, and nonspecific inflammation are known to
      be potential determinants for long-term islet survival and insulin independence.
      Sufficient islet mass is a key determinant. But islet engraftment and
      posttransplant survival may also depend on functional characteristics of the
      graft. This study investigated the significance of current product release
      criteria for the transplantation outcome. METHODS: Fourty five consecutive
      transplanted human islet preparations and their functional outcomes were
      analyzed. Islet mass was determined according to standard criteria: purity by
      light microscopy, viability by dye exclusion and Insulin secretory response to
      static glucose incubation. Islet graft function was monitored for > or = 1 year.
      Islet function was defined as full (FF), partial (PF), or nonfunction (NF) based
      on serum C-peptide levels and insulin independence. RESULTS: All islet grafts
      displayed primary function. Islet mass [IEQ/kg BW]: 7331.3 +/- 679.7 (FF), 5821.3
      +/- 546.7 (PF), 6468.6 +/- 658.5 (NF), (FF vs PF p = .032) Purity [%] 86.9 +/-
      3.1 (FF), 76.0 +/- 2.87 (PF), 88.2 +/- 2.3 (NF) (FF vs PF P =.045, PF vs NF, P =
      0.01). (4) Viability [%]:89.2 +/- 2 (FF), 86.2 +/- 1.7 (PF), 87.3 +/- 1.8 (NF)
      (ns). Stimulation index (SI): 20 +/- 6.3 (FF), 80.2 +/- 28.2 (PF), 21.6 +/- 3.5
      (NF) (ns) No correlation was observed between SI and any other parameter nor
      between SI and C-peptide levels. Islet mass significantly correlated with C
      peptide levels at 6 and 12 months after transplantation for functioning grafts.
      CONCLUSIONS: Stringent product release criteria allow identification of islet
      preparations suitable for clinical transplantation. However, currently used
      parameters are not predictive of long-term graft function, indicating that
      further refined quality assessments including apoptosis and resistance to early
      inflammation, are required to assess the primary engrafted islet mass.

PMID- 15251378
TI  - Assessment of human pancreatic islets after long distance transportation.
AB  - Pancreatic islet transplantation can replace functional insulin-secreting beta
      cells for patients with type 1 diabetes. More than 300 patients who have received
      islet transplantation have returned to a euglycemic condition without using
      insulin. Therefore, islet transplantation has gained public attention and
      interest. Unfortunately, shortages in organ donations, suboptional antirejection
      regimens, and difficulties in islet isolation limit clinical utilization of this
      therapy. Recently, successful islet transplantation has been reported using a
      centralized islet isolation facility. The advantage of this experience is that it
      avoids the high costs in building an isolation facility and maintaining an
      experienced technical team. However, a private airplane carrier was required for
      transporting islets back to the transplantation site in a remote hospital. The
      cost of this specialized transportation was still too high to be considered as a
      routine procedure. In this study, we report our experience using commercial
      carriers to deliver isolated human islets from an established isolation facility
      to a remote medical center.

PMID- 15251379
TI  - Augmentation of interleukin-10 in pancreatic islets after brain death.
AB  - Clinical islet transplantation is now established as a treatment for patients
      with type I diabetes. Although organs from brain-dead (BD) donors are the main
      source for clinical transplantation, marginal status after BD produces
      deterioration of the organs followed by molecular activation. The effect of brain
      death (BD) induction on the immunological status of donor islets was investigated
      using a rodent model of BD. BD animals showed decreased levels of peripheral
      white blood cells (WBC) compared to controls, indicating the extravasation of
      these cells (7270 +/- 500 vs 9570 +/- 370, respectively). In a densitometric
      study of RT-PCR products, the Th2 cytokine (IL-10) was significantly up-regulated
      in BD (2.91 +/- 0.26 vs 1.76 +/- 0.40), but a Th1 cytokine (IL-2) showed minimal
      change. Increased expression of IL-10 may inhibit macrophage function. As the
      marginal status after BD deteriorates, the islets of these donors may display
      early graft loss or poor long-term function. Integrative studies of
      immunomodulation might be necessary to eliminate islet infiltrates.

PMID- 15251380
TI  - Metaanalysis of statins and survival in de novo cardiac transplantation.
AB  - BACKGROUND: The use of HMG CoA reductase inhibitors (statins) after cardiac
      transplantation has been suggested to decrease the incidence of severe rejection
      and improve survival. Individual investigations that have led to this suggestion
      are randomized (but not placebo-controlled) studies, including small patient
      numbers that have (and thus underpowered) and enrolling heterogeneous subjects
      (including retransplant recipients). The purpose of this pooled analysis was to
      quantify the benefit of statins on survival in de novo cardiac transplant
      recipients. METHODS: Medline (1966 to 2003) was queried using the keywords
      statin, HMG CoA reductase inhibitors, cardiac transplantation, transplant,
      cholesterol, atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin.
      In addition, we searched the cited literature and previously published systematic
      reviews. Of 36 articles retrieved, 3 randomized controlled studies met our
      population inclusion criteria; namely age >18 years, de novo heart transplant
      recipients, statin therapy within 3 months, and > or = 1-year follow-up. Pooled
      data were metaanalyzed by Mantel-Haenszel tests using a random effects model that
      included tests for heterogeneity. RESULTS: The three pooled studies included 246
      patients (statin, n = 129; no statin, n = 117) and 27 events (11%). The pooled
      analysis demonstrated a significant reduction in mortality with statin use (RR
      0.31; 95% CI 0.13 to 0.7; P = .006) without significant heterogeneity (P = .7)
      among the studies. Two of the three studies reported allograft rejection with
      hemodynamic compromise. The pooled analysis demonstrated a significant benefit on
      this endpoint (RR 0.22, 95% CI 0.08 to 0.63; P = .004). CONCLUSION: This meta
      analysis demonstrates that statin therapy decreases rejection episodes with
      hemodynamic consequences and improves 1-year heart transplant survival.

PMID- 15251381
TI  - Transplant "twins": the experience of sharing transplanted thoracic organs from
      the same donor.
AB  - BACKGROUND: Many thoracic transplant recipients who receive organs from the same
      donor share facilities for 3 months, and are aware that they have received organs
      from the same donor. METHODS: A confidential questionnaire including open and
      closed questions assessed relationships between "twins" and the experience of
      having a twin. The Significant Others Scale assessed social support. Of 141 heart
      and 58 lung transplants, 25 pairs of transplant twins were identified.
      Questionnaires were sent to the 32 surviving twins. RESULTS: Twenty-six twins
      responded; 17 had received a heart and nine a lung. The 17 men and 9 women had a
      mean age of 51 years. Eighteen respondent's "twins" remained alive at the time of
      participation and eight had died. Sixty-six percent of the both- twin alive group
      and 43% of one-twin alive group felt they had a special bond with their twin,
      different from the other relationships that they have experienced. Fifty-six
      percent of the both-twin alive group and 43% of one-twin alive group felt having
      a twin enriched their transplant experience. Transplant twins rated social
      support last behind: the transplant support personnel; close family members;
      other transplant recipients; and good friends and general practitioners, both in
      levels of ideal and actual support. Transplant twins showed the largest
      discrepancy between levels of ideal and actual support than any other individual
      ranked. CONCLUSIONS: Being a transplant twin is a special experience that
      generally enriches the overall transplant experience but having a transplant
      twin, does not appear to enhance the amount of social support.

PMID- 15251382
TI  - Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal
      impairment.
AB  - BACKGROUND: A common clinical problem following organ transplantation is the
      development of renal failure due to calcineurin inhibitors. Sirolimus offers the
      potential of providing appropriate immunosuppression without nephrotoxicity. This
      study evaluates the impact of sirolimus monotherapy on renal function in patients
      late following heart transplantation and correlates trough sirolimus levels with
      area-under-the-concentration time curve measurements. METHODS: Six male patients
      with renal impairment late following heart transplantation (mean 8 years) were
      offered sirolimus therapy. Calcineurin inhibition was discontinued in all
      patients on commencing sirolimus. Patients started on sirolimus 2 to 5 mg/d
      orally. Venous blood samples for pharmacokinetic studies and repeat creatinine
      clearance were performed before and 6 weeks after commencement of sirolimus in
      all subjects. RESULTS: Sirolimus trough levels accurately reflected sirolimus
      area-under-the-concentration time curve measurements. There was no change in
      renal function. Mean creatinine clearance prior to commencing sirolimus was 26.7
      (12.2) mL/min and the post-sirolimus creatinine clearance performed 6 weeks later
      was 23.4 (11.7) mL/min (P = .64). CONCLUSIONS: Trough levels of sirolimus
      correlate with drug exposure and may be used to monitor sirolimus therapy. No
      improvement in renal function following calcineurin inhibitor withdrawal occurred
      in this cohort.

PMID- 15251383
TI  - How an undiscovered extensive peripheral pulmonary venous thrombosis destroyed a
      heart transplant: a case report.
AB  - This report details a recent experience with a 56-year-old man affected by an
      incompetent mitral valve due to Barlow's disease. The patient underwent a mitral
      valve repair and extracorporeal membrane oxygenator (ECMO) assistance due to
      postcardiotomy cardiogenic shock. During the ECMO assistance he experienced a
      left atrial thrombosis. A few days later, being unaware of the pulmonary vein
      thrombosis, we transplanted the patient, who ultimately died due to multiorgan
      failure and coagulopathy. This article highlights both the vain experience with
      ECMO and the uselessness of heart transplant, to avoid in the future an
      irresponsible waste of donor organs, as occurred in the current case.

PMID- 15251384
TI  - Solid organ transplantation across the ABO histo-blood group barrier: a case
      report.
AB  - The ABO blood group system until recently constituted an insuperable barrier for
      solid organ transplantation, but cases of heart transplantation in infants and
      kidney transplantation in adults have been reported, wherein ABO-incompatible
      grafts have been successful. In 1990, the molecular genetic basis of three major
      alleles at the ABO locus was elucidated; A and B glycosyltransferases are
      specified by a variety of functional alleles at this locus. The antibody response
      to ABH antigens, namely, naturally occurring anti-A/B IgM and IgG isotype
      agglutinins, are controlled preoperatively by recipient conditioning using plasma
      exchange, immunoadsorption, and immunosuppressive regimens. We report an O-type
      patient who accidentally received a B-type cardiac allograft in 1997 who survived
      for 5 years, dying for an unrelated reason. Over a period of 45 months
      semiquantitatively we monitored the expression of ABO-type antigens in graft
      heart vessels using monoclonal antibodies on sections of formalin-fixed, paraffin
      embedded biopsies. We observed a progressive change in the antigenic profile of
      graft endothelial cells from B- to O-type, which was first detected at 1 year
      posttransplant and most prominent 3 years later, the end of the observation
      period. No temporal relationship was observed between the transition from B to O
      expression, the anti-B antibody levels or the immunosuppressive regimen.

PMID- 15251385
TI  - Expanded use of transplantation techniques: abdominal wall transplantation and
      intestinal autotransplantation.
AB  - Surgical principles and techniques derived from organ transplantation surgery can
      provide novel applications in general surgery. We present an update on our 5-year
      experience with intestinal autotransplantation and abdominal wall
      transplantation. Nine patients underwent intestinal or multivisceral
      transplantation with the addition of 10 abdominal wall grafts to cover the large
      open areas from previous surgeries. Seven patients underwent near-total abdominal
      evisceration, ex vivo resection of masses at the base of the mesentery, followed
      by intestinal autotransplantation; 44% of the abdominal wall graft recipients are
      alive, but none of the fatalities were related to the graft itself. In two cases
      the graft had to be removed due to venous thrombosis. Of patients with intestinal
      autotransplants, 71% are alive with two mortalities due to recurrent metastatic
      malignancy. In only one case, the intestinal autograft had to be removed because
      of venous thrombosis. All surviving patients but one are on a regular diet; two
      are on supplemental enteral feeds. These results show that anastomotic and
      resection techniques derived from the experience in solid organ transplant can be
      utilized in complex wound closure, as is the case of abdominal wall
      transplantation, or resection of large retroperitoneal tumors with intestinal
      autotransplantation.

PMID- 15251386
TI  - Protective effect of ulinastatin against ischemia-reperfusion injury in rat small
      bowel transplantation.
AB  - INTRODUCTION: We aimed, to evaluate the protective effects of ulinastatin (UTI)
      against graft ischemia-reperfusion injury in rat small bowel transplantation
      (SBT). METHODS: Thirty-six recipients of rat SBT were randomly divided into three
      groups: 1, normal control, the graft was implanted immediately after harvest; 2,
      grafts preserved for 4 hours; and 3, grafts preserved for 4 hours and UTI
      administered to the recipients intravenously (50000 U/kg/d). Variables included
      pathological score and content of Na+-K+-ATPase, xanthine oxidase (XOD),
      malondialdehyde (MDA) and glutathione (GSH) in the transplanted small intestine.
      RESULTS: The cold preservation caused moderate injury to the graft which was
      manifested by pathological changes as well as elevated XOD and MDA and decreased
      Na+-K+-ATPase and GSH content. Application of UTI diminished these changes.
      CONCLUSIONS: UTI may exert protective effects against the ischemia-reperfusion
      injury of transplanted small intestine thereby promoting structural and
      functional recovery of the graft.

PMID- 15251387
TI  - Hickman catheter site infections after allogeneic stem cell transplantation: a
      single-center experience.
AB  - Hickman catheter site infections are known to increase transplant-related
      mortality. A retrospective analysis of 103 patients who received allogeneic stems
      cell transplants was performed to define the incidence and outcomes of Hickman
      infections. Seventy-six patients received peripheral blood stem cells (PBSC)
      (73.8%) and 29 patients (28.2%) nonmyeloablative conditioning. During the median
      follow-up of 9 months, Hickman infections were observed in 10 patients (9.7%) at
      a median onset of 32 days posttransplant (range 2 to 102 days). The causative
      organisms identified in five cases included Staphylococcus species (n = 4) and
      Pseudomonas aeruginosa (n = 1). Six events successfully resolved with antibiotic
      treatment, while the other four required the removal of the Hickman catheter with
      subsequent death in two cases. The survival duration for infected patients was
      shorter than that for the noninfected group (83 days vs 366 days, P < .001).
      Myeloid engraftment was delayed in the infected group (18.0 days vs 15.0 days, P
      = .038) and this complication was more frequently observed among the BMT compared
      with PBSC group (22.2% vs 5.3%, P = .019). Hickman infections were associated
      with transplant-related mortality especially during the first 3 months
      posttransplant. As such, the current results emphasize both the importance of
      Hickman catheter care and the need for surveillance cultures after stem cell
      transplantation.

PMID- 15251389
TI  - Effects of plastic-adherent dermal multipotent cells on peripheral blood
      leukocytes and CFU-GM in rats.
AB  - Multipotent cells were isolated from the dermis of newborn rats by their
      adherence to plastic culture dishes. Morphological observations showed that most
      of these elements were fibroblast-like cells described as cultured dermal
      multipotent cells (DMCs). These cells express CD90, CD44, CD59, intercellular
      adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1).
      They display the capacity to differentiate into cells with the phenotypic
      properties of osteocytes, adipocytes, chondrocytes, or neurons depending upon the
      specific inducing media. The confluent dermal multipotent cell layer supported
      and promoted the in vitro growth of colony-forming unit of granulocyte/macrophage
      progenitors (CFU-GM) as well as hematopoietic progenitor colonies.
      Transplantation of dermal multipotent cells into sublethally irradiated rats led
      to a significant increase of peripheral blood white cells nucleated cells, and
      CFU-GM colonies in the bone marrow. Fluorescence in situ hybridization analysis
      using a Y-chromosome-specific probe showed that dermal multipotent cells could
      engraft into bone marrow. However, they failed to differentiate into CD45
      positive hematopoietic cells and to repopulate the hematopoietic system of
      lethally irradiated rats. These results suggest that plastic-adherent DMCs may at
      least represent an alternative source of mesenchymal stem cells to restore the
      marrow microenvironment and promote the survival, engraftment, and proliferation
      of hematopoietic cells.

PMID- 15251388
TI  - Allogeneic hematopoietic cell transplantation from alternative donors in children
      with myelodysplastic syndrome: is that an alternative?
AB  - Allogeneic hematopoietic cell transplantation (HCT) in children with
      myelodysplastic syndrome (MDS) remains a challenge due to the toxic conditioning
      regimens administered to minimize the risk of relapse in the HLA-matched or of
      graft rejection in the HLA-mismatched settings. In the absence of matched sibling
      donors, alternative donors such as unrelated and/or partially matched family
      sources remain risky, yet the only available, options. Herein we report the
      results of HCT from alternative donors in 14 children with different subtypes of
      MDS (juvenile myelomonocytic leukemia [JMML] n = 9; myelodysplastic syndrome
      [MDS] refractory anemia n = 3; MDS refractory anemia with excess of blasts in
      transformation n = 2) transplanted at our institution. The median time from
      diagnosis to HCT was 9 months (range 4 to 90 months). The variety of HCT types
      included: unrelated peripheral blood progenitor cell transplantation (PBPCT) (n =
      2), partially matched family donor T-cell-repleted BMT/PBPCT (n = 6), and
      haploidentical T-cell-depleted PBPCT (n = 6). Five of 14 patients remain alive at
      7 to 37 months posttransplant (including two patients after partially matched
      family donor BMT, two patients after haploidentical T-cell-depleted-PBPCT, and
      one after unrelated-PBPCT, respectively). The major complications were: primary
      graft failure in the haploidentical T-cell-depleted-setting or graft-versus-host
      disease (GvHD) in T-cell-repleted partially matched family or unrelated settings,
      respectively. Despite the high transplant-related mortality rate in this series,
      allogeneic HCT from alternative donors remains an interesting solution for
      children with MDS who lack matched sibling donors. Due to improved immune
      reconstitution, despite an increased risk of GvHD, T-cell-repleted transplants
      from single HLA-mismatched family donors remain a valuable option for children
      without matched donors. Splenectomy prior to HCT may positively affect the
      posttransplant course in patients with overt splenomegaly for example those
      afflicted with JMML.

PMID- 15251390
TI  - Vascular cell adhesion molecule-1-targeted detection of endothelial activation in
      human microvasculature.
AB  - The hallmark of endothelial activation, an early and critical step in many
      alloimmune and inflammatory responses, is the transcriptional induction and
      expression of endothelial adhesion molecules (eg, vascular cell adhesion molecule
      1 [VCAM-1]). We assessed the feasibility of VCAM-1-targeted in vivo detection of
      endothelial activation using I-125-labeled-F(ab')2 fragments of E1/6, a
      monoclonal antibody against human but not murine VCAM-1. The Kd and Bmax,
      determined by saturation binding in tumor necrosis factor (TNF)-activated human
      endothelial cells (ECs), were 3.2 +/- 0.6 nmol/L and 5600 +/- 300 binding sites
      per EC, respectively. Biodistribution and in vivo binding characteristics of I
      125-E1/6 F(ab')2 were assessed in a novel chimeric human/mouse model, in which
      human skin (as a source of human microvasculature) is grafted onto SCID/beige
      mice. I-125-E1/6 F(ab')2 localized to TNF-activated human skin grafts as detected
      by autoradiography and gamma well-counting. Relative uptakes (uptake in human
      skin graft/uptake in the surrounding mouse skin) were, respectively, 2.6 +/- 0.8
      (n = 14) and 1.6 +/- 0.3 (n = 12) for E1/6 and MOPC-21, an isotype-matched
      control antibody (P < .01). The preferential uptake in human skin graft was not
      due to differences in tissue vascularity assessed by Tc-99m-labeled murine red
      blood cells. In conclusion, the chimeric human/mouse model is a novel
      experimental tool for in vivo evaluation of human endothelial cell-specific
      radiopharmaceuticals. Although I-125-E1/6 F(ab')2 localized to human skin grafts,
      the limited number of VCAM-1 molecules/endothelial cell adversely affects its
      suitability as a target for in vivo imaging of endothelial activation.

PMID- 15251391
TI  - Application of recipient-derived dendritic cells to induce donor-specific T-cell
      hyporesponsiveness.
AB  - Administration of donor-derived immature dendritic cells (DC) treated with NF
      kappaB oligodeoxyribonucleotides (ODN) prevents allograft rejection. We attempted
      to explore the use of recipient-derived DC pulsed with donor antigens, in which
      the donor antigens were presented to host T cells via an indirect pathway (cross
      priming). Expression of CD40, CD80, and CD86 on DC was significantly inhibited by
      treatment with NF-kappaB ODN, whereas MHC class I and II were minimally affected.
      Normal C3H DC pulsed with B10 antigens stimulated proliferative responses and
      donor-specific CTL activity in C3H T cells, both of which were, however, markedly
      inhibited when DC were treated with NF-kappaB ODN. This manipulation was
      associated with reduced IFN-gamma and increased IL-10 production in the
      supernate, suggesting a Th2 bias. More frequent apoptotic T cells were observed
      in cultures with NF-kappaB ODN DC. In contrast to administration of normal DC
      pulsed with donor antigens that accelerated rejection of B10 cardiac allografts
      (median survival time [MST] 7 days versus 10 days in no-DC treatment control, P <
      .05), a single injection of 2 x 10(6) NF-kappaB ODN DC significantly prolonged
      allograft survival (MST 50 days, P < .05 compared with no-DC treatment control).
      The anti-donor CTL activity in infiltrating T cells isolated from cardiac grafts
      in recipients that received NF-kappaB ODN DC was significantly suppressed. These
      data indicate that vaccination with immature DC, propagated from recipient BM is
      an attractive approach to induce T-cell hyporesponsiveness.

PMID- 15251392
TI  - Assessment of tissue-engineered stomach derived from isolated epithelium organoid
      units.
AB  - OBJECTIVE: Isolated stomach epithelial organoid units developed on biodegradable
      polymers were transplanted to assess the feasibility of a tissue-engineered
      stomach. BACKGROUND: Despite recent advances in reconstruction techniques, total
      gastrectomy is still accompanied by various complications. An alternative
      treatment would be a tissue-engineered stomach, which replaces the mechanical and
      metabolic functions of a normal stomach. METHODS: Stomach epithelial organoid
      units isolated from neonatal rats were seeded onto biodegradable polymers. The
      constructs implanted into the omenta of adult rats were harvested for examination
      at designated times. Nine rats underwent a second operation for anastomosis.
      RESULTS: The constructs resulted in cyst-like formations showing vascularized
      tissue with neomucosa lining the lumen. The surface morphology as assessed using
      scanning electron microscopy was similar to that of a native stomach.
      Immunohistochemical staining for alpha-actin smooth muscle and gastric mucin
      indicated the presence of a smooth muscle layer and a well-developed gastric
      epithelium, respectively. The luminal surface of the anastomosed tissue
      engineered stomach was well-covered with epithelium. CONCLUSIONS: Epithelium
      derived stomach organoid units seeded on biodegradable polymers and transplanted
      into donor rats were shown to vascularize, survive, and regenerate into complex
      tissue resembling native stomach. Anastomosis between the units and native small
      intestine may have the potential to stimulate epithelial growth. This research
      may provide insight into new approaches to alleviate complications following
      total gastrectomy.

PMID- 15251393
TI  - Gene transfer of interleukin-4 delays acute rejection of splenic allografts in
      rats.
AB  - Spleen transplantation is the treatment of choice for some diseases, such as
      hemophilia A. However, the risk and intensity of rejection after spleen
      transplantation is greater and more difficult to control than other types of
      transplant. In the present study, we demonstrated that perfusion of IL-4
      expression plasmids into donor spleens pretransplantation led to overexpression
      of IL-4 and downregulation of IFN-gamma in situ, associated with delayed acute
      rejection of the allograft. Gene transfer of IL-4 may represent a potential
      therapeutic approach to induce tolerance to splenic allografts.

PMID- 15251394
TI  - Prevention of murine acute graft-versus-host disease by recipient-derived
      TGFbeta1-treated dendritic cells.
AB  - Acute graft-versus-host disease (GVHD) remains the major barrier to allogeneic
      bone marrow transplantation (allo-BMT). Evidence has accumulated that
      transforming growth factor beta1-treated dendritic cells (TGFbeta-DC), deficient
      in surface costimulatory molecules, inhibit alloantigen-specific T-cell responses
      and induce graft hyporeactivity. To analyze the effect of TGFbeta-DC on GVHD
      after allo-BMT, 5.0 x 10(6) recipient-derived TGFbeta-DC were injected into
      C57BL/6 (H-2b) with bone marrow-splenocyte grafts from major histocompatibility
      complex (MHC) disparate BALB/c mice (H-2d). Survival analysis showed TGFbeta-DC
      cotransplantation resulted in significant prolongation of allograft survival,
      namely a mean survival time (MST) of 44.3 +/- 4.5 days, versus the untreated MST
      of 9.5 +/- 0.6 days (P < .01). However, mature DC aggravated the GVHD with an MST
      of 6.6 +/- 0.6 days (P < .01). In addition, the third-party C3H-derived TGFbeta
      DC did not enhance the survival rate (MST = 9.7 +/- 0.5 days). Furthermore, serum
      IFN-gamma, IL-12, and IL-18 levels in TGFbeta-DC cotransplanted mice were reduced
      compared with untreated BMT hosts, while serum IL-10 levels were not changed.
      These results suggest that TGFbeta-DC cotransplantation may attenuate the
      severity of GVHD after BMT.

PMID- 15251395
TI  - Auxiliary liver-heart transplantation in the rat: a new microsurgical model
      inducing tolerance.
AB  - OBJECTIVE: To establish a model of immunological tolerance induced by
      simultaneous auxiliary liver transplantation and heterotopic heart
      transplantations using PVG and DA rats as donors and recipients respectively, to
      provide a new method for the research of liver transplantation. METHODS: The
      recipient's whole portal vein blood was transfered to the auxiliary liver
      allograft. The donor's heart was transplanted to the recipient's abdominal cavity
      by end-to-side anastomosis of the donor aorta and pulmonary artery to the
      recipient aorta and vena cava, respectively. RESULTS: In the syngeneic control
      group and the test group the recipient rats and their transplanted hearts both
      survived more than 100 days, while the hearts of alloheart control group only
      survived 6 days. The weight of the liver graft increased slowly. CONCLUSIONS: In
      the presence of recipient liver, the auxiliary liver graft functioned well to
      induce tolerance. At 100 days, the auxiliary liver graft had increased in volume
      and weight with maintenance of its tolerance-inducing effects.

PMID- 15251396
TI  - MRI and histology of collagen template disc implantation and regeneration in
      rabbit temporomandibular joint: preliminary report.
AB  - INTRODUCTION: We aimed to evaluate regeneration of injured temporomandibular
      joint (TMJ) discs following reconstituted collagen template implantation in
      rabbits using contrast-enhanced magnetic resonance imaging (MRI) and to correlate
      these findings with histology. METHODS: Twenty-four adult rabbits were divided
      into five groups: group A, partial discectomy without implantation (n = 6); group
      B, partial discectomy with collagen template implantation (n = 6); group C,
      partial discectomy with subdermal graft implantation (n = 6); group D, sham
      operation (n = 4); and group E, control (n = 2). All rabbits received baseline
      MRI scans before surgery and follow-up MRI studies at 3 months after surgery. All
      rabbits were sacrificed for histologic analysis after the follow-up MRI. RESULTS:
      In group A, follow-up MRI showed marked joint effusion in all six injured TMJs,
      which was accompanied by bony erosion at the tympanic fossa and mandibular
      condyle. In group B, MRI showed a homogenous low signal intensity in five of six
      discs, suggestive of regeneration. One disc showed higher signal intensity at its
      lateral portion than that of the original disc, indicating partial regeneration.
      MRI of group C depicted a low signal intensity, bandlike regenerative structure
      in four of the six discs. One disc with partial regeneration demonstrated
      relatively high signal intensity. The disc in the sixth animal of this group
      showed no evidence of regeneration. All of the MRI findings were in agreement
      with the histologic findings. CONCLUSION: TMJ discs can regenerate following
      implantation of a reconstituted collagen template in discectomied rabbits.
      Contrast-enhanced MRI can be used to monitor and determine the degree of disc
      regeneration.

PMID- 15251397
TI  - Effect of human somatotropin hormone on cultured rat islets.
AB  - Because growth hormone (GH) improves the insulin secretion capacity of isolated
      human fetal islets in vitro, we sought to show that it positively influences
      isolated rat islets. Islets isolated from Wistar albino rats by a modified
      automated system were cultured in media containing 87% RPMI 1640, 10% FCS, 2%
      antibiotic-antimycotic, and 1% L-glutamine for 12 +/- 2 days. The cultured islets
      were divided into two groups: growth hormone negative (Group I) and growth
      hormone positive (Group II). On the 5th day we observed a decrease in the islet
      cell counts in both groups (Group I 28% versus Group II 45%). On the 10th day,
      the decrease continued in the GH-negative group (59%), while the count remained
      stable in the GH-positive group. The viability of rat islets was determined by
      fluorescein diacetate (FDA) plus propidium iodide (PI) staining. In comparison to
      the peripheral green, central orange-red staining pattern of Group I islets upon
      fluorescent microscopy, Group II showed more compact islets. Cultured islets
      seemed to be brighter than those without GH in the cultured islets. In
      conclusion, we observed that 2 weeks of incubation in the presence of GH acts
      positively on cultured rat islets for both their amount and their viability.

PMID- 15251398
TI  - Artemether in the treatment of falciparum malaria during pregnancy in eastern
      Sudan.
AB  - This study was carried in New Halfa Hospital, eastern Sudan from October 1997 to
      February 2001. Twenty-eight pregnant Sudanese women infected with Plasmodium
      falciparum were treated with intramuscular artemether (six injections, 480 mg)
      after failure of chloroquine and quinine therapy. The patients were followed-up
      until delivery; the babies were followed-up until the age of 1 year. Artemether
      was given to one patient in the tenth week of gestation, to 12 during the second
      trimester, and to 15 during the third trimester. It was well tolerated, the
      parasitaemia was cleared and the patients were symptom-free within three days.
      One patient (3.5%) delivered at 32 weeks and the baby died six hours after
      delivery. The other 27 (96.5%) delivered full-term live babies. None of the
      pregnant women died and there was no abortion, stillbirth or congenital
      abnormalities in the newborn babies.

PMID- 15251399
TI  - Human schistosomiasis mansoni: intensity of infection differentially affects the
      production of interleukin-10, interferon-gamma and interleukin-13 by soluble egg
      antigen or adult worm antigen stimulated cultures.
AB  - The effect of the intensity of infection (eggs per gram faeces, epg) on the
      production of interferon-gamma (INF-gamma), interleukin (IL)-10 and IL-13 by
      peripheral blood mononuclear cells (PBMCs) from individuals living in a
      Schistosoma mansoni-endemic area was evaluated. In vitro stimulation of PBMCs
      with soluble egg antigen (SEA) resulted in significantly higher secretion levels
      of IFN-gamma in egg-negative individuals compared with those with an intensity of
      infection of more than 100 epg. In contrast, the egg-positive group produced
      significantly higher amounts of IL-10. Levels of IL-13 did not differ
      significantly between egg-positive and egg-negative groups. These findings
      suggest that IL-10 is an important cytokine in the control of the T helper cell
      (Th) type 1 responses during human S. mansoni infection, shifting the immune
      response from Th0 in egg-negative individuals from an endemic area to a Th2
      polarization in chronic infected individuals.

PMID- 15251400
TI  - Impact of four years of large-scale ivermectin treatment with low therapeutic
      coverage on the transmission of Onchocerca volvulus in the Mbam valley focus,
      central Cameroon.
AB  - The extent to which ivermectin treatments have an impact on onchocerciasis
      transmission is a matter of some concern. We investigated this issue in the Mbam
      valley, a hyperendemic focus located in a forest-savannah mosaic area of
      Cameroon. Parasitological examinations of 5-9-year-old children, who had never
      received any antifilarial drug, were conducted before the first distribution of
      ivermectin in 1991-1993 and again in 2002, after four annual rounds of mass
      treatments. After matching for gender, age and village of residence, the
      prevalence and intensity of microfilaridermia corresponded respectively, in 2002,
      to 66.2 and 42.0% of the initial values. The decrease was more marked among the
      youngest children who, compared with the older ones, were submitted to the
      reduced force-of-infection earlier in their life. The results of the present
      study suggest that the specific vectorial competence of Simulium squamosum
      cytotype B, the vector of Onchocerca volvulus in the Mbam valley, allows a
      significant decrease in onchocerciasis transmission after several years of
      treatment, despite low therapeutic coverage. Though these results are
      encouraging, efforts should be made to improve the therapeutic coverage in the
      area.

PMID- 15251401
TI  - Failure of chloramphenicol prophylaxis to reduce the frequency of abscess
      formation as a complication of envenoming by Bothrops snakes in Brazil: a double
      blind randomized controlled trial.
AB  - Bites by many species of venomous snake may result in local necrosis at, or
      extending from, the site of the bite. The use of prophylactic antibiotics to
      prevent infection as a complication of local necrotic envenoming is
      controversial. A double-blind randomized controlled trial was carried out to
      assess whether antibiotic therapy is effective in this situation. Two hundred and
      fifty-one patients, with proven envenoming by snakes of the genus Bothrops,
      admitted to two hospitals in Brazil, between 1990 and 1996, were randomized to
      receive either oral chloramphenicol (500 mg every six hours for five days) or
      placebo. One hundred and twenty-two of these patients received chloramphenicol
      (group 1) and 129 were given placebo (group 2). There were no significant
      differences between the groups at the time of admission. Necrosis developed in
      seven (5.7%) patients in group 1 and in five (3.9%) patients in group 2 (P>0.05)
      while abscesses occurred in six patients (4.9%) in group 1 and in six (4.7%)
      patients in group 2 (P>0.05). In conclusion, the use of orally-administered
      chloramphenicol for victims of Bothrops snake bite with signs of local envenoming
      on admission, is not effective for the prevention of local infections.

PMID- 15251402
TI  - Intra-household clustering of hepatitis C virus infection in Karachi, Pakistan.
AB  - Transmission rates of hepatitis C virus (HCV) infection through non-sexual
      household contacts have been considered to be very low. This study evaluated
      intra-household clustering of cases of HCV infection in a low socio-economic
      community in Karachi, Pakistan. Serum samples from 341 household contacts of 86
      thalassaemic HCV-seropositive children were evaluated for antibodies to HCV using
      an ELISA. Spatial analysis of data was carried out to test for intra-household
      clustering. Seventy of 341 (20.5%) household contacts were HCV-seropositive. Of
      the households studied, 44.2% (38/86) had one or more contacts who tested HCV
      seropositive. Ecological analysis of variables at household level showed that in
      households where HCV-seropositive index thalassaemic children were male HCV
      tended to be transmitted to one or more familial contacts. Spatial analysis with
      an asymptotic score test of the null hypothesis of no extra within-family
      infectivity revealed that there was a significant tendency of HCV infection to
      cluster within a household (score statistic = 19.44, P=0.032). The results showed
      that non-sexual household exposure may play a role in efficient HCV spread to
      household contacts of HCV-infected persons and needs further evaluation.

PMID- 15251403
TI  - Is praziquantel therapy safe during pregnancy?
AB  - Schistosomiasis control programmes are generally based on mass distribution of
      praziquantel (PZQ). This approach has been further strengthened by studies that
      demonstrated reduction in schistosomiasis-related morbidity following regular use
      of PZQ. Many women were excluded from this therapy when pregnant. Since a high
      degree of parity is achieved in many schistosomiasis-endemic regions, excluded
      women often miss treatment and consequently the beneficial effect of this
      therapy. This study investigated the effect of PZQ therapy on pregnancy in the
      Gezira region of Sudan. As part of the Blue Nile Health Project, more than
      320,000 individuals received annual treatment with PZQ from 1980 to 1990. The
      present study reviewed the treatment records of all women between 1990 and 1995
      in four villages. Eighty-eight of 637 women interviewed had received PZQ during
      their pregnancy. The outcome and the effect of PZQ therapy on their offspring
      were compared with a group of 549 women who had not received the drug during
      pregnancy. There were no significant differences between the two groups in the
      rate of abortion or preterm deliveries. No congenital abnormalities were noted by
      clinical examination in any of the babies born to either group. This
      retrospective study suggested that PZQ therapy is safe during pregnancy.

PMID- 15251404
TI  - HIV infection among paediatric in-patients in Blantyre, Malawi.
AB  - To investigate the impact of HIV infection on hospital admission and death we
      studied children admitted to paediatric medical and surgical wards in Blantyre,
      Malawi, in March 2000. Unselected children whose parents or guardians consented
      to HIV testing of the child were recruited and HIV infection was determined by
      serology, with confirmation in children aged 15 months or less by PCR. We
      assessed the prevalence of HIV infection by age, clinical diagnosis and outcome
      of admission. Of 1064 admissions, 991 were tested for HIV infection, and 187
      (18.9%) were infected. HIV was most common in children aged less than six months,
      53 of 166 (32%). Parents of HIV-infected children were better educated, and more
      likely to have died, than those of uninfected children. Clinical symptoms and
      signs were not adequately sensitive or specific to be used for diagnosis of HIV.
      HIV was common in children with malnutrition (prevalence 40%), lower respiratory
      tract infection (29%) and sepsis (28%), and less prevalent among children with
      malaria (11%) or surgical admissions (11%). Almost 30% of HIV-infected children
      died, compared with 8.9% of uninfected children, and HIV-infected children
      constituted over 40% of in-patient deaths.

PMID- 15251405
TI  - Dengue virus surveillance: the co-circulation of DENV-1, DENV-2 and DENV-3 in the
      State of Rio de Janeiro, Brazil.
AB  - This study presents the results obtained in the monitoring of dengue virus (DENV)
      transmission in the Greater Metropolitan Region of the State of Rio de Janeiro,
      in the period 2000-2001. A total of 5324 serum samples from suspected cases of
      dengue were analysed in order to confirm dengue infection. The introduction of
      DENV-3 to the region in December 2000 resulted in the co-circulation of three
      serotypes: DENV-1, DENV-2 and DENV-3. In this study, virus isolation and/or
      reverse transcriptase PCR (RT-PCR) confirmed 52.3% (42/79) of DENV-3 cases,
      showing the importance of acute serum samples in the virological surveillance of
      the disease. Despite the introduction of a new serotype, an outbreak due to DENV
      1 was observed in the municipality of Niteroi. The restriction site-specific PCR
      (RSS-PCR) patterns obtained for DENV-1 and DENV-2 isolated in that period showed
      that those strains belonged to the subtypes previously circulating in the state.
      DENV-3 RSS-PCR patterns confirmed that these viruses belonged to subtype C (Sri
      Lanka/India strains), represented by the strain circulating on the American
      continent. These data showed the importance of an active surveillance programme
      in countries where dengue is endemic.

PMID- 15251406
TI  - A cholera epidemic in a rural area of northeast India.
AB  - Sporadic cases of acute diarrhoea with high morbidity occur commonly in rural
      areas of northeast India, throughout the year. At times they take epidemic form
      and one such outbreak occurred with attack and case fatality rates of 11.6% and
      0.8%, respectively, in October 2002, in a remote locality of Assam. Vibrio
      cholerae O1 El Tor Ogawa was isolated in 63% of hospitalized acute diarrhoea
      patients. Ineffective antibacterial treatment, poor hygiene practices and bad
      peridomestic sanitation were the factors associated with the persistence and
      spread of the pathogen, leading to the outbreak of cholera, resistant to commonly
      used antimicrobials.

PMID- 15251407
TI  - Recommendations for the design and optimization of immunoassays used in the
      detection of host antibodies against biotechnology products.
AB  - Most biopharmaceutical therapeutics elicit some level of antibody response
      against the product. This antibody response can, in some cases, lead to
      potentially serious side effects and/or loss of efficacy. Therefore, the
      immunogenicity of therapeutic proteins is a concern for clinicians, manufacturers
      and regulatory agencies. In order to assess immunogenicity of these molecules,
      appropriate detection, quantitation and characterization of antibody responses
      are necessary. Inadequately designed antibody assays have led to the hampering of
      product development or, during licensure, post-marketing commitments. This
      document provides scientific recommendations based on the experience of the
      authors for the development of anti-product antibody immunoassays intended for
      preclinical or clinical studies. While the main focus of this document is assay
      design considerations, we provide scientific focus and background to the various
      assay performance parameters necessary for developing a valid assay. Sections on
      assay performance parameters, including those that appear in regulatory
      guidances, are contained in this manuscript.

PMID- 15251408
TI  - A novel flow cytometric assay focusing on perforin release mechanisms of
      cytotoxic T lymphocytes.
AB  - CD8(hi+) cytotoxic T lymphocytes (CTL) are major players in immune defense. In
      addition, they contribute to the maintenance of immune homeostasis. We now
      describe a hitherto unavailable, but simple assay to determine ex vivo lytic
      granule-based cytotoxic functions of human CD8(hi+) CTL subgroups in a clinical
      setting, under target cell free conditions. Ficoll-isolated peripheral blood
      lymphocytes from 17 healthy volunteers were stimulated either by phorbol 12
      myristate 13-acetate (PMA) in combination with ionomycin or by antibody mediated
      crosslinking of the CD3 molecule on the T cell surface. Using perforin as a
      marker for lytic granules, the reduction of CTL granules over time intervals up
      to 120 min was quantified by FACScan flow cytometry. The kinetics of perforin
      reduction were compared to the kinetics of NA-CBZ-L-lysine-thiobenzyl ester
      hydrochloride (BLT)-esterase release and of CD63 upregulation. The reduction in
      the perforin(+) portion of CD8(hi+) CTLs was correlated inversely with BLT
      esterase release and CD63 upregulation. At 30 and 120 min after PMA/ionomycin
      stimulation, 55 +/- 14% and 42 +/- 14%, respectively, of CD8(hi+) CTLs still
      stained perforin(+) (time point 0 min = 100%). Perforin-granule release induced
      by CD3-crosslinking occurred as fast within 30 min (55 +/- 17%), but over the 120
      min time interval it was not as complete when compared to PMA/ionomycin
      stimulated perforin-reduction. Thus, the combination of an established
      degranulation assay with the power of immuno flow cytometry allows one to
      investigate the cytotoxic capability of CTL-subtypes and the kinetics of perforin
      granule release. In addition, the assay may prove useful in the elucidation of
      intracellular signaling cascades governing the perforin-granule release process.

PMID- 15251409
TI  - Development of immunofiltration assay by light addressable potentiometric sensor
      with genetically biotinylated recombinant antibody for rapid identification of
      Venezuelan equine encephalitis virus.
AB  - A genetically biotinylated single chain fragment variable antibody (scFv) against
      Venezuelan equine encephalitis virus (VEE) was applied in a system consisting of
      an immunofiltration enzyme assay (IFA) with a light addressable potentiometric
      sensor (LAPS) for the rapid identification of VEE. The IFA involved formation of
      an immunocomplex sandwich consisting of VEE, biotinylated antibody,
      fluoresceinated antibody and streptavidin, capture of the sandwich by filtration
      on biotinylated membrane, and labeling of the sandwich by anti-fluorescein urease
      conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies
      was investigated and optimized. By the IFA/LAPS assay, the limit of detection
      (LOD) of VEE was approximately 30 ng/ml, similar to that achieved when chemically
      biotinylated monoclonal antibody (mAb) was applied. Total assay variance of the
      IFA/LAPS assay for both intra- and inter-assay precision was less than 20%. Assay
      accuracy was measured by comparing VEE concentrations estimated by IFA/LAPS
      standard curve to those obtained by conventional protein assay. VEE
      concentrations were found to differ by no more than 10%. The IFA/LAPS assay
      sensitivity was approximately equal to that of a conventional enzyme-linked
      immunosorbent assay (ELISA) utilizing polystyrene plates and a chromogenic
      substrate; however, less time and effort were required for performance of the
      IFA/LAPS assay. More importantly, use of genetically biotinylated scFv in the
      IFA/LAPS assay obviates the need for chemical biotinylation of antibody with
      resultant possible impairment of the antigen-binding site. Furthermore, the
      potential for batch-to-batch variability resulting from inequality in the number
      of biotin molecules labeled per antibody molecule is eliminated.

PMID- 15251410
TI  - Assembly of targeting complexes driven by a single-chain antibody.
AB  - Rapid development in design and production of recombinant antibodies and antibody
      fragments specific for cell surface markers opens new opportunities for targeted
      delivery of therapeutic or imaging agents. However, the progress in this field is
      slowed by inactivation of many antibodies by chemical conjugation of payloads and
      by lack of internalization of complexes formed on the cell surface. Here, we
      describe conversion of a non-internalizing single chain Fv (scFv) antibody P4G7
      specific for vascular endothelial growth factor receptor 2 (VEGFR-2) into a
      targeting protein (Hu-P4G7) for assembly of a novel type of targeting complexes.
      Hu-P4G7 contains an N-terminal "docking" Hu-tag, a 15-aa fragment of human RNase
      I, capable of high affinity binding of S-protein fragment of human RNase I or
      bovine RNase A. Purified Hu-P4G7 and complexes of Hu-P4G7 with S-protein bind
      both soluble and full-length cellular VEGFR-2. To assemble targeted DNA delivery
      complexes, S-protein modified with a DNA condensing agent was "docked" to Hu
      P4G7, and then loaded with luciferase plasmid DNA. As expected for a non
      internalizing targeting protein, Hu-P4G7-based complexes did not deliver DNA in
      VEGFR-2 expressing cells. However, in the presence of vascular endothelial growth
      factor (VEGF), these complexes selectively delivered DNA into the cells
      overexpressing VEGFR-2 suggesting that even a non-internalizing scFv antibody can
      be used for targeted intracellular drug delivery.

PMID- 15251411
TI  - Flow cytometric measurement of neutrophil respiratory burst in whole bovine blood
      using live Staphylococcus aureus.
AB  - A rapid and simple method for measurement of respiratory burst in neutrophil
      granulocytes in whole bovine blood is described. The respiratory burst was
      stimulated by live Staphylococcus aureus, and the production of reactive oxygen
      species quantified by the conversion of intracellular dihydrorhodamine 123 to the
      green fluorescent rhodamine 123, measured by flow cytometry. Assay conditions,
      including bacterial and dihydrorhodamine 123 concentrations and incubation time,
      were determined. Repeatability and precision of the method were assessed by
      testing parallel samples from clinically healthy dairy cows. In vitro and in vivo
      inhibition of respiratory burst was investigated, and labelling with a
      granulocyte marker antibody was performed. Stimulation with live S. aureus
      induced green fluorescence in the neutrophil granulocytes in a whole blood
      preparation. The fluorescence intensity increased with increasing bacterial
      concentration and increasing incubation time. Agreement analysis showed that the
      method gave repeatable results, and the intra-assay variability of the method was
      relatively low. The method is considered a useful technique for measurement of
      neutrophil respiratory burst in whole bovine blood.

PMID- 15251412
TI  - Determination of human complement3 by solid substrate room temperature
      phosphorescence immunoassay with a labelled avidin-biotin bridge.
AB  - A solid substrate room temperature phosphorescence immunoassay (SS-RTP-IA) for
      the determination of human complement3 (C3) based on a sandwich type assay and a
      labelled avidin-biotin (LAB) type assay was described. The anti-human complement3
      and avidin were labeled with eosin5-isothiocyanate. On a polyamide membrane (PM),
      SS-RTP signals (lambda(ex)/lambda(em) = 535/678 nm) of immune complexes obtained
      by both assays were linear with the concentration of complement3 in the range of
      6.25-100 ng/ml. The detection limits are 1.37 ng/ml for sandwich assay and 2.74
      ng/ml for labeled avidin-biotin assay. (For a sample volume of 0.4 microl per
      spot, the mass detection limits are 0.546 and 1.09 pg/spot, respectively. If the
      molecular weight of human complement3 is 185,000, the detection limits are 2.95
      and 5.91 amol per spot.) The results of determination of complement3 in 20 human
      sera obtained by labeled avidin-biotin SS-RTP-IA are correlated well with those
      obtained by ELISA. This study shows that SS-RTP-IA by whichever direct, sandwich
      or labeled avidin-biotin type assay can combine very well the characteristics of
      both the high sensitivity of SS-RTP and specificity of the immunoreaction.

PMID- 15251413
TI  - Rapid generation of functional human IgG antibodies derived from Fab-on-phage
      display libraries.
AB  - We introduce a procedure for the rapid generation of fully human antibodies
      derived from "Fab-on-phage" display libraries. The technology is based on the
      compatibility of display vectors and IgG expression constructs, and allows
      reformatting of individual Fab clones to IgG, as well as reformatting of antibody
      repertoires. Examples of batch reformatting of an uncharacterized Fab repertoire
      and of a pool of Fabs, previously analyzed at the phage level, are presented. The
      average transient expression levels of the IgG constructs in HEK293T cells are
      above 10 microg/ml, allowing the use of conditioned media in functional assays
      without antibody purification. Furthermore, we describe a high-throughput
      purification method yielding IgG amounts sufficient for initial antibody
      characterization. Our technology allows the generation and production of antigen
      specific complete human antibodies as fast or even faster than raising monoclonal
      antibodies by conventional hybridoma techniques.

PMID- 15251414
TI  - Single step high-throughput determination of Toll-like receptor 4 polymorphisms.
AB  - BACKGROUND: Toll-like receptors are central components of host defence in humans,
      responsible for recognition of pathogen-associated molecular patterns and
      activation of innate immunity. Toll-like receptor 4 (TLR4) is activated by
      lipopolysaccharide (LPS) and other microbial components, thereby initiating the
      expression and release of pro-inflammatory cytokines. The common, frequently co
      segregating allelic variants Asp299Gly and Thr399Ile have been related to
      susceptibility to gram-negative infections and sepsis and may be involved in the
      development of atherosclerosis. Identification of TLR4 Asp299Gly and Thr399Ile
      genotypes can be important for examination of genotype/phenotype relationships as
      well as for individual risk assessment of patients. METHODS: TLR4 Asp299Gly and
      Thr399Ile genotypes were detected by a single tube polymerase chain reaction
      (PCR), based on exonuclease degradation of dual labelled allele-specific
      oligonucleotides. The assay results were compared with conventional restriction
      fragment length polymorphism (RFLP) analysis. RESULTS: Genotypes of 345
      individuals were determined simultaneously in a single PCR assay. Allele
      frequencies for our population were 6.8% for the TLR4 Asp299Gly polymorphism and
      6.4% for the Thr399Ile polymorphism. Validation by RFLP analysis revealed a
      correct detection of all genotypes. CONCLUSIONS: We have developed a novel method
      for the detection of the TLR4 Asp299Gly and Thr399Ile mutations, permitting rapid
      genotyping which should be useful for large-scale population studies as well as
      applicable for routine clinical testing.

PMID- 15251415
TI  - A fast and simple dot-immunobinding assay for quantification of mouse
      immunoglobulins in hybridoma culture supernatants.
AB  - Mouse monoclonal antibodies of IgG subclasses and IgM class in hybridoma culture
      supernatants were quantified using a dot-immunobinding assay. Immunoglobulins
      were bound to nitrocellulose (NC) membrane and, after blocking, the membrane was
      incubated with anti-mouse antibody conjugated to horseradish peroxidase (HRP).
      Binding was revealed by incubation with a sensitive chemiluminiscence reagent.
      Quantitation was achieved by densitometric comparison with standard curves
      produced by purified monoclonal antibodies of the same subclass or purified
      antibodies of the same clone as the antibody to be quantified. These quantitative
      results were compared with those obtained using purified IgG from mouse serum or
      purified mouse myeloma IgM as standards. The dot-immunobinding assay requires 1
      microl of hybridoma culture sample and takes about 1 h in total. Good linearity
      between the staining intensity and the amount of immobilized immunoglobulins was
      observed over the range of 0.05-5 ng/spot. The assay is simple, reproducible and
      can process simultaneously a large number of samples.

PMID- 15251416
TI  - Three new assays for rituximab based on its immunological activity or antigenic
      properties: analyses of sera and plasmas of RTX-treated patients with chronic
      lymphocytic leukemia and other B cell lymphomas.
AB  - Rituximab (RTX) is a monoclonal antibody which targets CD20 and is approved for
      treatment of non-Hodgkin's lymphoma (NHL), with an approximate 50% overall
      response rate among NHL patients. Accurate determination of RTX concentrations in
      patient plasmas is important for proper dosing of patients and for correlating
      RTX concentrations with clinical responses. There is currently no assay available
      for RTX which utilizes easily obtainable commercial reagents. Therefore, we
      sought to develop such an assay, and in this report we describe three new assays
      for RTX concentration. One assay, based on flow cytometry, quantitates
      immunologically active RTX based on its ability to bind to CD20 on Raji cells.
      Two other methods, based on flow cytometry and ELISA, measure RTX based on its
      antigenic properties. The assays are accurate, in good agreement with one
      another, and can all measure RTX concentrations as low as approximately 1
      microg/ml in both sera and plasmas. Use of these assays reveals that chronic
      lymphocytic leukemia (CLL) patients receiving RTX treatment have lower plasma RTX
      concentrations than patients with other B cell lymphomas at all times over the
      usual 4-week course of therapy. The level in CLL plasmas often declines to <1
      microg/ml RTX 1 week after each RTX infusion, substantially lower than the values
      found in comparable non-CLL patient plasmas. RTX assay results also demonstrate
      that naive CLL patient plasmas do not have levels of non-cell associated CD20
      sufficient to either interfere with an in vitro assay of RTX or to block the
      potential therapeutic action of RTX in vivo.

PMID- 15251417
TI  - The immunogenicity of recombinant and dimeric gonadotrophin-releasing hormone
      vaccines incorporating a T-helper epitope and GnRH or repeated GnRH units.
AB  - In this study, we designed two linear peptides, GnRH-hinge-MVP, which consists of
      human gonadotrophin-releasing hormone (GnRH), hinge fragment 225-232/225'-232' of
      human IgG1 and a T helper peptide from measles virus protein (MVP), and GnRH3
      hinge-MVP, which contains three copies of GnRH (so termed GnRH3). The DNA
      constructs encoding for the two peptides were fused to the C-terminal encoding
      sequence of asparaginase, encompassing residues 199-326, through an acid-labile
      aspartyl-prolyl linker. The chimeric genes were expressed at high levels in
      Escherichia coli. The fusion proteins were purified to approximate homogeneity by
      means of washing the inclusion bodies and by ethanol precipitation. The GnRH
      hinge-MVP or the GnRH3-hinge-MVP was released from the fusion proteins by
      cleavage with hydrochloric acid and further oxidized into double-chain
      miniproteins after purification. Both dimeric constructs proved to be efficient
      immunogens. It was shown that rats immunized with the immunogens generated
      antibodies specific for GnRH. The dimeric GnRH3-hinge-MVP containing three copies
      of GnRH in each chain induced a higher titre of anti-GnRH antibodies than the
      GnRH-hinge-MVP, containing a single copy of GnRH in each chain. These results
      demonstrate that combining multicopies or single copies of peptide with hinge
      fragment of human IgG and T helper peptide from measles virus protein can induce
      anti-peptide immune responses. Our data also suggest that these methods of
      preparation and dimerization of the recombinant polypeptides may provide a useful
      strategy for other polypeptide vaccine developments.

PMID- 15251418
TI  - In vitro evaluation of the effects of candidate immunosuppressive drugs: flow
      cytometry and quantitative real-time PCR as two independent and correlated read
      outs.
AB  - BACKGROUND: Immune monitoring may use flow cytometry or molecular biology
      techniques. Flow cytometry assays cells that are phenotypically characterized,
      whereas TaqMan RT-PCR starts with RNA extraction from unfractionated
      heterogeneous cell populations. We therefore wondered how the effects of
      immunosuppressive drugs on cytokine production in stimulated whole blood, as
      determined by flow cytometry, would correlate with those obtained with
      quantitative real-time PCR (TaqMan RT-PCR). METHODS: Blood drawn from naive
      cynomolgus monkeys was exposed to incremental amounts of cyclosporine (CsA; 300,
      600, 900 and 1200 ng/ml) or tacrolimus (TRL; 8, 20, 40 and 80 ng/ml) before
      lectin stimulation in vitro. Blood was then either stained for CD3, IFN-gamma, IL
      2, IL-4, and TNF-alpha and analyzed on a flow cytometer with various gating
      strategies, or submitted to RNA extraction for analysis of the above mentioned
      cytokines mRNA transcripts using TaqMan RT-PCR. RESULTS: Both methods revealed a
      parallel dose-dependent inhibition of cytokine production in stimulated blood.
      The 50% inhibitory concentrations (IC(50)'s) ranged from 511-771 ng/ml (CsA) and
      15-29 ng/ml (TRL) with flow cytometry, and from 275-529 ng/ml (CsA) and 11-48
      ng/ml (TRL) with TaqMan RT-PCR for T-helper 1 cytokines. Both assays correlated
      well with a Pearson product moment correlation of 0.76. Extending gating from a
      CD3(+) gate to a lymphocyte gate improved correlation (r = 0.85) for all
      cytokines investigated (except IL-2; unchanged) whereas further extending gating
      resulted, to the contrary, in lower correlations. Independent of gating strategy
      a high correlation (r = 0.97) was observed when drug IC(50)'s were considered.
      CONCLUSIONS: Flow cytometry and TaqMan RT-PCR may be used interchangeably to
      monitor the effects of candidate immunosuppressive drugs on cytokine mRNA
      production in lectin-stimulated whole blood.

PMID- 15251420
TI  - Single-chain Fv antibody with specificity for Listeria monocytogenes.
AB  - Single chain antibodies (scFv) exhibiting specific binding to Listeria
      monocytogenes strains were isolated from a pool of random scFvs expressed on the
      surface of filamentous bacteriophages. Positive selection (panning) using L.
      monocytogenes was used to enrich for phage clones with the desired binding
      affinity, and negative selection using L. innocua and L. ivanovii was used to
      remove phages expressing cross-reactive antibody fragments. A single phage clone,
      P4:A8, was selected using two independent panning schemes. A rapid assay was
      devised to determine phage antibody binding specificity and was used to develop a
      selectivity profile for individual phage clones. The P4:A8 clone was screened
      against a panel of bacteria consisting of eight strains of L. monocytogenes, one
      each of the other six species of Listeria and nine other relevant bacterial
      species. A collection of individual clones from the penultimate panning was also
      screened against a subset of the panel of bacteria. The selectivity profiles
      indicate that multiple clones, including P4:A8, exhibit binding to one or more
      strains of L. monocytogenes without cross-reactivity toward any other species in
      the panel. This is the first report of a species-specific antibody for viable
      cells of L. monocytogenes (i.e., the ability to bind to L. monocytogenes without
      cross-reactivity toward any other species of Listeria).

PMID- 15251419
TI  - Phage-display selection of antibodies to the left end of CTX3C using synthetic
      fragments.
AB  - Ciguatoxins (CTXs) are a family of toxins that contaminate a variety of fish and
      cause ciguatera seafood poisoning. The limited availability of CTXs from natural
      sources has hampered preparation of antibodies and, thus, the development of
      immunoassays for these toxins. In the current studies, we utilized synthetic
      fragments as haptens to prepare antibodies against CTX3C, a congener of CTXs,
      thereby avoiding the problem of its scarcity. Synthetic ABC-ring fragment (ABC)
      of CTX3C was conjugated with keyhole limpet hemocyanin (KLH) and immunized on
      mice. Phage-displayed antibodies were first screened based on affinity to a
      soluble biotin-linked ABC-ring fragment that was captured on streptavidin-linked
      magnetic beads. The beads were then eluted with the ABCD-ring fragment (ABCD),
      and recovered phages were amplified. This elution with a synthetic fragment
      allowed the preparation of antibodies to ABCD as well as to ABC. Three antibodies
      with affinities of K(d) approximately 10(-5) M for ABCD were selected and
      prepared as soluble recombinant Fabs (rFabs). One rFab, 1C49, bound to CTX3C
      itself, although the binding affinity for CTX3C was weaker than for ABCD.

PMID- 15251421
TI  - Characterization of monoclonal antibodies against prostate specific antigen
      produced by genetic immunization.
AB  - Prostate specific antigen (PSA) is the most important marker for prostate cancer.
      Antibodies against minor variants of PSA may be useful in the development of
      novel diagnostic tests for prostate cancer, but it has been difficult to produce
      such antibodies by protein immunization. In this study, we have compared the
      characteristics of monoclonal antibodies (MAbs) obtained by genetic immunization
      with those obtained by protein immunization. The whole coding region of PSA-cDNA
      was cloned in a mammalian expression vector pCDNA-3. Six mice were immunized four
      times by intra-muscular (i.m.) injection of the PSA-pCDNA3 plasmid. The MAbs
      produced were characterized with respect to subclass, epitope specificity,
      binding to various molecular forms of PSA and affinity. After intra-muscular
      injection of DNA, anti-PSA antibodies were detected in the serum of all mice, but
      the antibody titers were markedly lower than after protein immunization. After
      fusion of the spleen cells from the mice, five hybridomas producing MAbs to PSA
      were obtained. The MAbs were of IgG1 and IgG2a isotype and they all recognized
      equally different forms of free PSA, namely enzymatically active, nicked and
      proPSA. Epitope mapping showed that these MAbs reacted with the same antigenic
      regions as those obtained by protein immunization. Thus, genetic immunization
      leads to production of anti PSA MAbs with similar characteristics to those
      obtained by immunizing with PSA protein. As applied in the present study, it is
      less efficient than protein immunization, but it is a useful technique when the
      antigen is not available in the quantities needed for immunization.

PMID- 15251422
TI  - Detection of low-abundance membrane markers by immunofluorescence--a comparison
      of alternative high-sensitivity methods and reagents.
AB  - The analysis of membrane molecules using antibodies detected by
      immunofluorescence staining and flow cytometry is used widely in research and
      diagnostic immunology. Conventional staining techniques readily detect molecules
      present at concentrations of around 2000 molecules per cell, but some molecules
      are expressed and function at much lower abundance. We described previously a
      method for the detection of molecules present at 100 molecules per cell or less
      based on the use of phycoerythrin as the fluorophore, a three-layer amplification
      process, and careful selection of available reagents. In recent years, a number
      of new reagents, fluorophores and kits, have become available, some of them
      intended for high-sensitivity applications. In this paper, a number of these
      reagents have been compared with the published method. While some of the reagents
      gave variable results or high nonspecific staining in our hands, several reagents
      were comparable with the published method. Furthermore, the new fluorophores
      allow improved simultaneous detection of two low-abundance markers.

PMID- 15251423
TI  - Human tonsillar tissue block cultures differ from autologous tonsillar cell
      suspension cultures in lymphocyte subset activation and cytokine gene expression.
AB  - Lymphoid tissues cultured either as tissue blocks or as cell suspensions are used
      to study the behaviour of immune cells within their habitat. The preservation of
      tissue structures in tissue blocks, which is considered to be a major advantage,
      has been poorly defined. We characterised the morphological evolution of tissue
      cultures from human palatine tonsils and compared their lymphocyte subsets and
      the constitutive cytokine gene expression to those in autologous tonsillar single
      cell suspension cultures over time, and after adding cyclosporin A (CsA) to mimic
      the situation in individuals treated with immunosuppressive drugs. Density and
      morphology of follicles were conserved up to 4 days, during which tissue cultures
      exhibited similar cell viability as suspension cultures, but a significantly less
      frequent increase of CD95 expression in T cells, smaller variation of the
      proportion of CD4(+) cells and better CD21(+)/CD23(-) B-cell survival. Treatment
      with cyclosporin A at higher concentrations resulted in superior histologic
      preservation of lymphoid tissue structures and seemed to further prevent the
      expression of CD95 by CD3(+) cells and the activation in tissue culture of
      CD21(+) cells. Constitutive gene expression levels of the stromal cytokines
      interleukin (IL)-1beta and interleukin-6 in tissue culture were significantly
      higher than those in suspension cultures. These results suggest that tonsillar
      tissue cultures preserve their structure only for a limited time, during which
      they more closely reflect processes in vivo, including a state of iatrogenic
      immunosuppression, than do their cell suspension counterparts.

PMID- 15251424
TI  - CrELISA: a fast and robust enzyme-linked immunosorbent assay bypassing the need
      for purification of recombinant protein.
AB  - A multitude of antigens has been recently identified by screening of cDNA
      expression libraries derived from human tumors with autologous sera. Using a
      phage autoantibody assay and small panels of sera derived from cancer patients or
      controls it has been shown that some of these antigens display cancer-associated
      autoantibody responses. The diagnostic and prognostic significance of these
      potentially cancer-related autoantibodies remains unclear until large-scale
      assays are developed and serological data are available for hundreds of cancer
      patients and controls. The major bottleneck for the development of large-scale
      assays are the cloning, expression and the purification of each of the respective
      antigens. Due to these limitations and despite the potential clinical relevance
      large-scale autoantibody tests are established for only a few of these tumor
      antigens. Here we describe an enzyme-linked immunosorbent assay, Crude lysate
      ELISA (CrELISA), suitable for antigens identified by expression screening based
      on crude lysates of antigen-expressing bacteria. This assay permits sensitive and
      specific autoantibody seroscreening without the need of laborious and time
      consuming cloning, expression and purification of recombinant proteins. CrELISA
      is robust and provides a versatile high throughput procedure for the rapid
      evaluation of multiple antigens in large-scale serology.

PMID- 15251425
TI  - Quantitation of complement and leukocyte binding to a parasitic helminth species.
AB  - Methods used to quantify complement deposition and cell adherence to parasitic
      helminths usually involve subjective visual comparisons of immunofluorescence or
      time-consuming manual counting of bound cells. Such targets are relatively large
      and, generally, few individual organisms can be analysed. More objective and
      efficient radiometric assays are available, but these also have considerable
      disadvantages. We have developed an improved immunofluorescence-based method for
      quantitation of complement deposition on viable third-stage larvae of the
      nematode Nippostrongylus brasiliensis (L3). A similar strategy was also applied
      to measuring leukocyte adherence to the parasite. Fluorescein isothiocyanate
      (FITC)-conjugated antibodies were used to detect complement on serum-treated
      larvae. The adherence of carboxyfluorescein diacetate succinimidyl ester (CFSE)
      labelled mouse leukocytes to larvae was investigated using the same basic
      approach. Images of fluorescent larvae or fluorescent cells attached to larvae
      were generated with a Bio-Rad Molecular Imager FX and fluorescence intensity was
      quantified. Hundreds of larvae can be analysed simultaneously in multiple
      samples, and these strategies allow rapid and sensitive quantitation that is
      directly proportional to the amount of protein or the number of leukocytes added
      to cultures. These techniques may also be applicable to other large objects,
      organisms or biological surfaces.

PMID- 15251426
TI  - Recombinant HMGB1 with cytokine-stimulating activity.
AB  - We describe methods for the isolation, purification, and characterization of full
      length high-mobility group box 1 (HMGB1) and truncated mutants expressed in
      bacteria and in mammalian Chinese Hamster Ovary (CHO) cells. HMGB1 is an abundant
      nuclear and cytoplasmic protein, highly conserved across species and widely
      distributed in eukaryotic cells from yeast to man. As a ubiquitous nuclear DNA
      binding protein, HMGB1 binds DNA, facilitates gene transcription, and stabilizes
      nucleosome structure. In addition to these intracellular roles, HMGB1 can be
      released into the extracellular milieu by activated innate immune cells (i.e.,
      macrophages, monocytes) and functions as a mediator of lethal endotoxemia and
      sepsis. The proinflammatory cytokine activity of HMGB1 has become an intense area
      of research and recombinant protein can be a useful tool to probe HMGB1
      functions. Due to its dipolar charged properties, HMGB1 isolated by some methods
      can be contaminated with bacterial products (such as CpG DNA or
      lipopolysaccharide [LPS]) that may interfere with immunological analyses. Here we
      report our newly developed methods for the isolation and purification of
      biologically active HMGB1 from bacteria or mammalian CHO cells that is
      essentially free of contaminants. This strategy provides an important advance in
      methodology to facilitate future HMGB1 studies.

PMID- 15251427
TI  - Use of immunodotting to select the desorption agent for immunochromatography.
AB  - In immunochromatography, a technique of increasing use, the sample containing the
      antigen (Ag) to be purified or determined is introduced into a chromatographic
      column containing an antibody (Ab) bound to the packing material. The antigen is
      retained based on antigen-antibody recognition. To reuse the immunocolumn for
      subsequent assays, the antigen has to be eluted without causing irreversible
      damage of antibodies. Selection of conditions for performing immunochromatography
      is usually made by trial and error. This way of working is time consuming and it
      may ruin the column. In this article, the feasibility of using immunodotting to
      select the conditions to be employed in one immunochromatographic assay is shown.
      An immunodotting method is developed to select the best desorption agent for an
      enzyme-linked immunoaffinity chromatography (ELIAC) assay to determine beta
      lactoglobulin (beta-LG). The effect of several factors on the immunodotting
      performance is studied. The way of performing solvent exchange to treat the
      antibody with different solutions considered as potential desorption agents to
      check their effect is shown. Effectiveness of the solution chosen by
      immunodotting (4 M MgCl(2) in 20 mM Tris, pH 5.9) as desorption agent is
      demonstrated by immunochromatographic assays. The immunodotting and solvent
      exchange methods developed should be useful to choose solvents and conditions for
      any other kind of assay.

PMID- 15251428
TI  - Quantification of vascular endothelial growth factor-C.

PMID- 15251429
TI  - Miraculous catch of iron-sulfur protein sequences in the Sargasso Sea.
AB  - Recent shotgun sequencing of filtered Sargasso Sea water samples has yielded data
      in astounding amount and diversity. Iron-sulfur proteins, which are ancient,
      diverse and ubiquitous, have been implemented here to further probe the sequence
      diversity of the Sargasso Sea database (SSDB). Sequence searches and comparisons
      confirm that the SSDB by and large equals in diversity the combined currently
      available databases. The data thus suggest that microbial diversity has so far
      been underestimated by orders of magnitude.

PMID- 15251430
TI  - ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA
      damage agents in HepG2 cells.
AB  - The known members of inhibitor of growth (ING) gene family are considered as
      candidate tumor suppressor genes. ING4, a novel member of ING family, is recently
      reported to interact with tumor suppressor p53, p300 (a major component of
      histone acetyl transferase complexes), and p65(RelA) subunit of NF-kappaB. In
      this study, we investigated the cellular behaviors of HepG2 cells with exogenous
      ING4. Interestingly, the overexpression of ING4 negatively regulated the cell
      growth with significant G2/M arrest of cell cycle, and moreover, enhanced the
      cell apoptosis triggered by serum starvation in HepG2 cells. Furthermore, the
      exogenous ING4 could upregulate endogenous p21 and Bax in HepG2 cells, not in p53
      deficient Saos-2 cells, suggesting that G2/M arrest induced by ING4 could be
      mediated by the increased p21 expression in a p53-dependent manner, although
      there is no significant increase of p53 expression in HepG2 cells. Moreover,
      HepG2 cells with exogenous ING4 could significantly increase cell death, as
      exposed to some DNA-damage agents, such as etoposide and doxorubicin, implying
      that ING4 could enhance chemosensitivity to certain DNA-damage agents in HepG2
      cells.

PMID- 15251431
TI  - Structures of Bacillus subtilis PdaA, a family 4 carbohydrate esterase, and a
      complex with N-acetyl-glucosamine.
AB  - Family 4 carbohydrate esterases deacetylate polymeric carbohydrate substrates
      such as chitin, acetyl xylan and peptidoglycan. Although some of these enzymes
      have recently been enzymologically characterised, neither their structure nor
      their reaction mechanism has been defined. Sequence conservation in this family
      has pointed to a conserved core, termed the NodB homology domain. We describe the
      cloning, purification and 1.9 A crystal structure of PdaA, a peptidoglycan
      deacetylase from Bacillus subtilis. The enzyme assumes a fold related to a
      (beta/alpha)8 barrel, with a long groove on the surface of the protein that
      harbours all conserved residues. A complex with the substrate analogue N-acetyl
      glucosamine was refined to 2.25 A resolution, revealing interactions of an
      aspartic acid and three histidines, all conserved in the NodB homology domain,
      with the ligand. The PdaA structure provides a template for interpreting the
      wealth of sequence data on family 4 carbohydrate esterases in a structural
      context and represents a first step towards understanding the reaction mechanism
      of this family of enzymes.

PMID- 15251432
TI  - Phorbol ester-induced translocation of PKC epsilon to the nucleus in fibroblasts:
      identification of nuclear PKC epsilon-associating proteins.
AB  - We show that phorbol ester treatment of NIH 3T3 fibroblasts induces rapid
      translocation of PKC from a perinuclear site to the nucleus, extending findings
      in PC12 and NG108-15 cells and in myocytes. We have immunoprecipitated the PKC
      from nuclei isolated from phorbol ester-treated fibroblasts and identified six
      proteins which associate with nuclear PKC. These have been characterised as
      matrin 3, transferrin, Rac GTPase activating protein 1, vimentin, beta-actin and
      annexin II by MALDI-TOF-MS. We have confirmed that these proteins associate with
      PKC by gel overlay and/or dot blotting assays. The role of these PKC-associating
      proteins in the nucleus and their interaction with PKC are considered.

PMID- 15251433
TI  - Increased plasma HDL cholesterol levels and biliary cholesterol excretion in
      hamster by LCAT overexpression.
AB  - Lecithin cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of
      high density lipoprotein (HDL), which has been found inversely correlated with
      atherosclerosis. Adenovirus mediated overexpression of human LCAT (hLCAT) in
      hamsters resulted in increased levels of plasma total cholesterol, HDL
      cholesterol, phospholipids and enlarged particle size of HDL. It also increased
      cholesterol and total bile acid concentrations in bile. Hepatic mRNA level of
      cholesterol 7alpha-hydroxylase increased 2.7-fold in hamsters. However, such
      effects were not observed in mice in a parallel experiment. This study suggests
      that overexpression of hLCAT in hamsters facilitated reverse cholesterol
      transport. Similar metabolic changes in humans might modify atherogenic risk.

PMID- 15251434
TI  - Cryptic endotoxic nature of Bacillus thuringiensis Cry1Ab insecticidal crystal
      protein.
AB  - Cry1Ab is one of the most studied insecticidal proteins produced by Bacillus
      thuringiensis during sporulation. Structurally, this protoxin has been divided in
      two domains: the N-terminal toxin core and the C-terminal portion. Although many
      studies have addressed the biochemical characteristics of the active toxin that
      corresponds to the N-terminal portion, there are just few reports studying the
      importance of the C-terminal part of the protoxin. Herein, we show that Cry1Ab
      protoxin has a unique natural cryptic endotoxic property that is evident when
      their halves are expressed individually. This toxic effect of the separate
      protoxin domains was found against its original host B. thuringiensis, as well as
      to two other bacteria, Escherichia coli and Agrobacterium tumefaciens.
      Interestingly, either the fusion of the C-terminal portion with the insecticidal
      domain-III or the whole N-terminal region reduced or neutralized such a toxic
      effect, while a non-Cry1A peptide such as maltose binding protein did not
      neutralize the toxic effect. Furthermore, the C-terminal domain, in addition to
      being essential for crystal formation and solubility, plays a crucial role in
      neutralizing the toxicity caused by a separate expression of the insecticidal
      domain much like a dot/anti-dot system.

PMID- 15251435
TI  - Histone deacetylase inhibitors regulate p21WAF1 gene expression at the post
      transcriptional level in HepG2 cells.
AB  - Histone deacetylase inhibitors (HDIs) are thought to act primarily at the level
      of transcription inducing cell cycle arrest, differentiation and/or apoptosis in
      many cancer cell types. Induction of the potent cdk/cyclin inhibitor p21WAF1 is a
      key feature of this HDI mediated transcriptional re-programming phenomenon.
      However, in the current study we report that HDIs are also capable of inducing
      p21WAF1 through purely post-transcriptional events, namely increased mRNA
      stability. These studies highlight our growing appreciation for the complexities
      of HDI mediated effects and challenge our preconceptions regarding the action of
      these promising anti-neoplastics.

PMID- 15251436
TI  - On the origin of the electrostatic barrier for proton transport in aquaporin.
AB  - The nature of the electrostatic barrier for proton transport in aquaporins is
      analyzed by semimacroscopic and microscopic models. It is found that the barrier
      is associated with the loss of the generalized solvation energy upon moving from
      the bulk solvent to the center of the channel. It is clarified that our solvation
      concept includes the effect of the protein polar groups and ionized residues. The
      nature of the contributions to the solvation barrier is examined by using the
      linear response approximation. It is found that the residues in the NPA region
      contribute much less than what would be deduced from calculations that do not
      consider the protein reorganization. It is clarified that the contributions of
      different structural or electrostatic elements to the solvation barrier can be
      established by removing these elements and examining the corresponding effect on
      the barrier height. Using this definition and "mutating" the NPA residues to
      their non-polar analogues establishes that these residues do not provide the
      major contribution to the solvation barrier.

PMID- 15251437
TI  - Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo.
AB  - CCL15 is a novel human CC chemokine and exerts its biological activities on
      immune cells through CCR1 and CCR3. Because a number of chemokines induce
      angiogenesis and endothelial cells express CCR1 and CCR3, we investigated the
      angiogenic activity of CCL15. Both CCL15(1-92) and N-terminal truncated CCL15(25
      92) stimulate the chemotactic endothelial cell migration and differentiation, but
      CCL15(25-92) is at least 100-fold more potent than CCL15(1-92). Treatment with
      pertussis toxin (PTX), with anti-CCR1, or with anti-CCR3 antibody inhibits the
      CCL15(25-92)-induced endothelial cell migration. CCL15(25-92) also stimulates
      sprouting of vessels from aortic rings and mediates angiogenesis in the chick
      chorioallantoic membrane assay. Our findings demonstrate that CCL15(25-92) has in
      vitro and in vivo angiogenic activity, and suggest roles of the chemokine in
      angiogenesis.

PMID- 15251438
TI  - Control of superoxide production in mitochondria from maize mesocotyls.
AB  - To understand the biochemical events that control the generation of superoxide,
      the effect of inhibiting the respiratory complexes III and IV (C-III and C-IV)
      and alternative oxidase (AOX) on the rate of superoxide production was analyzed
      in mitochondria from maize seedlings. To increase superoxide production, it was
      required to inhibit C-III or C-IV by at least 30% or 50%, respectively. Below
      this inhibition threshold, AOX exerted the highest degree of control on
      superoxide production, whereas above it, the highest degree of control was
      exerted by C-IV. The contribution of C-III to control superoxide production
      became significant when AOX activity was modulated.

PMID- 15251440
TI  - GATA-3 suppresses IFN-gamma promoter activity independently of binding to cis
      regulatory elements.
AB  - The regulatory mechanism by which GATA-3 suppresses IFN-gamma gene expression was
      investigated. A reduction of GATA-3 using RNA interference technology enhanced,
      whereas overexpression of GATA-3 suppressed IFN-gamma mRNA expression. IL-4
      expression was reciprocally affected by GATA-3. GATA-3-mediated down-regulation
      of IFN-gamma was achieved through the inhibition of its promoter/enhancer
      activity. Two GATA elements located in the cis-regulatory elements did not
      contribute to the suppression of IFN-gamma promoter activity, even though they
      behaved as binding sites for GATA-3. The effect of GATA-3 on IFN-gamma promoter
      was lost upon removal of the region encompassing -257 to -172. Among several
      transcription factors putatively interacting with this region, Stat4, which
      enhanced IFN-gamma promoter activity, was down-regulated by GATA-3 at gene
      transcription level. Although GATA-3 has the capacity to interact with the cis
      regulatory elements, it suppresses IFN-gamma gene transcription via down
      regulation of Stat4.

PMID- 15251439
TI  - Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl
      phosphorofluoridate in the liver.
AB  - Senescence marker protein-30 (SMP30) was originally identified as a novel protein
      in the rat liver, the expression of which decreases androgen-independently with
      aging. We have now characterized a unique property of SMP30, the hydrolysis of
      diisopropyl phosphorofluoridate (DFP), which is similar to the chemical warfare
      nerve agents sarine, soman and tabun. Hydrolysis of DFP was stimulated equally
      well by 1 mM MgCl2, MnCl2 or CoCl2, to a lesser extent by 1 mM CdCl2 but not at
      all by 1 mM CaCl2. No 45Ca2+-binding activity was detected for purified SMP30,
      suggesting that SMP30 is not a calcium-binding protein, as others previously
      stated. Despite the sequence similarity between SMP30 and a serum paraoxonase
      (PON), the inability of SMP30 to hydrolyze PON-specific substrates such as
      paraoxon, dihydrocoumarin, gamma-nonalactone, and delta-dodecanolactone indicate
      that SMP30 is distinct from the PON family. We previously established SMP30
      knockout mice and have now tested DFPase activity in their livers. The livers
      from wild-type mice contained readily detectable DFPase activity, whereas no such
      enzyme activity was found in livers from SMP30 knockout mice. Moreover, the
      hepatocytes of SMP30 knockout mice were far more susceptible to DFP-induced
      cytotoxicity than those from the wild-type. These results indicate that SMP30 is
      a unique DFP hydrolyzing enzyme in the liver and has an important detoxification
      effect on DFP. Consequently, a reduction of SMP30 expression might account for
      the age-associated deterioration of cellular functions and enhanced
      susceptibility to harmful stimuli in aged tissue.

PMID- 15251441
TI  - Aldosterone rapidly activates Src kinase in M-1 cells involving the
      mineralocorticoid receptor and HSP84.
AB  - We investigated the effect of aldosterone on Src kinase. In the kidney cell line,
      M-1 aldosterone leads to a >2-fold transient activation of Src kinase seen as
      early as 2 min after aldosterone administration. Maximal Src kinase activation
      was measured at an aldosterone concentration of 1 nM. In parallel to activation,
      autophosphorylation at Tyr-416 of Src kinase increased. Src kinase activation was
      blocked by spironolactone. Aldosterone led to increased association of Src with
      HSP84. Furthermore, rapamycin blocked aldosterone-induced Src activation. We
      conclude that Src activation by aldosterone is mediated through the
      mineralocorticoid receptor and HSP84.

PMID- 15251442
TI  - Secretion of long Abeta-related peptides processed at epsilon-cleavage site is
      dependent on the alpha-secretase pre-cutting.
AB  - Abeta is the major component of amyloid in the brain in Alzheimer's disease and
      is derived from Alzheimer amyloid precursor protein (APP) by sequential
      proteolytic cleavage involving alpha-, beta- and gamma-secretase. Recently, gamma
      secretase was shown to cleave near the cytoplasmic membrane boundary of APP
      (called the epsilon-cleavage), as well as in the middle of the membrane domain
      (gamma-cleavage). However, the precise relationship between gamma- and epsilon
      cleavage is still unknown. In this paper, I analyzed Abeta-related peptides using
      immunoprecipitation and liquid chromatography ion trap mass spectrometer and
      found some long Abeta-related peptides, starting at Abeta residues 16Lys-23Asp
      and ending at 43Thr-52Leu, in the culture media of COS-1 cells and in human brain
      extract. These results indicated that longer Abeta-related peptides cleaved at
      epsilon-cleavage site were secreted under normal conditions and were dependent on
      the alpha-secretase cleavage products.

PMID- 15251443
TI  - Investigations on the binding and antioxidant properties of the plant flavonoid
      fisetin in model biomembranes.
AB  - Plant flavonoids are emerging as potent therapeutic drugs for free radical
      mediated diseases, for which cell membranes generally serve as targets for lipid
      peroxidation and related deleterious effects. Screening and characterization of
      these ubiquitous, therapeutically potent polyphenolic compounds, require a clear
      understanding regarding their incorporation and possible location in membranes,
      as well as quantitative estimates of their antioxidative and radical scavenging
      capacities. Here, we demonstrate the novel use of the intrinsic fluorescence
      characteristics of the plant flavonoid fisetin (3,3',4',7-OH flavone) to explore
      its binding and site(s) of solubilisation in egg lecithin liposomal membranes.
      Spectrophotometric assays have been used to obtain quantitative estimates of its
      antioxidative capacity. Furthermore, our quantum mechanical semi-empirical
      calculations provide a quantitative measure for the free radical scavenging
      activity of fisetin from the OH (at 3,3', 4', 7 positions of the molecule)-bond
      dissociation enthalpies. Implications of these findings are discussed.

PMID- 15251444
TI  - Phospholipase activity is modulated by c-Fos through substrate expansion and
      hyperpolarization.
AB  - c-Fos, a component of AP-1 transcription factors, has been shown to have marked
      amphitropic properties and to regulate phospholipase activity against lipid
      monolayers. In agreement with its high surface activity, it has also been found
      to associate to membranes of the endoplasmic reticulum and to activate
      phospholipid metabolism in vivo. All these findings point to an involvement of
      this oncoprotein within a membrane environment. We have previously shown that c
      Fos modulates in different manners the activity of phospholipase A2 and
      phospholipase C against monolayers of dilauroylphosphatidylcholine (PC). In this
      work, we have studied the possible molecular mechanism underlying the
      phosphohydrolytic modulation. Our results show that c-Fos expands and
      hyperpolarizes PC, indicating that its effects on these enzymatic activities are
      due to the changes it induces on the interfacial organization of the substrate.

PMID- 15251445
TI  - Facilitated folding and subunit assembly in Escherichia coli and in vitro of
      nucleoside diphosphate kinase from extremely halophilic archaeon conferred by
      amino-terminal extension containing hexa-His-tag.
AB  - We have previously reported that nucleoside diphosphate kinase (HsNDK) from
      extremely halophilic archaeon Halobacterium salinarum was expressed in
      Escherichia coli as a soluble, but inactive form and required high salt
      concentrations for in vitro folding and activation. Here, we found that fusion of
      extra sequence containing hexa-His-tag at amino-terminus of HsNDK (His-HsNDK)
      facilitated folding and activation of HsNDK in E. coli. This is a first
      observation of active folding of halophilic enzyme from extremely halophilic
      archaeon in E. coli. The in vitro refolding rate of His-HsNDK after heat
      denaturation was greatly increased over the native HsNDK. Folded His-HsNDK
      isolated from E. coli formed a hexamer in both 0.2 M and 3.8 M NaCl at 30 degrees
      C, while the native HsNDK purified from H. salinarum dissociated to dimer in 0.2
      M NaCl. The observed hexameric structure in 0.2 M NaCl indicates that amino
      terminal extension also enhances dimer to hexamer assembly and stabilizes the
      structure in low salt. These results suggest that positive charges in fused amino
      terminal extension are effective in suppressing the negative charge repulsion of
      halophilic enzyme and thus, facilitate folding and assembly of HsNDK.

PMID- 15251446
TI  - Inhibition of hexose transport and abrogation of pH homeostasis in the
      intraerythrocytic malaria parasite by an O-3-hexose derivative.
AB  - An O-3-hexose derivative, shown previously to inhibit a malaria parasite hexose
      transporter expressed in Xenopus oocytes as well as to suppress the
      multiplication of parasites, both in vitro and in vivo, was shown here to block
      the uptake of hexose sugars into isolated blood-stage parasites. This led to a
      decline in ATP levels and the loss of intracellular pH control. The results are
      consistent with those obtained with the cloned transporter. They support the
      notion that the transporter mediates uptake of glucose into the intraerythrocytic
      parasite and provide further support for the view that it is a suitable
      antimalarial drug target.

PMID- 15251447
TI  - PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis.
AB  - The TIR domain-containing adapter protein TRIP is critically involved in TLR3
      induced IFN-beta production through activation of NF-kappaB and ISRE. In
      addition, TRIF also induces apoptosis when overexpressed in 293 cells. In this
      report, we demonstrate that PIASy, a member of the PIAS SUMO-ligase family,
      interacts with TRIP, IRF-3 and IRF-7. In reporter gene assays, PIASy dramatically
      inhibits TRIF-induced NF-kappaB, ISRE and IFN-beta activation but not TRIF
      induced apoptosis. Furthermore, PIASy also inhibits IRF-3, IRF-7 and Sendai virus
      induced ISRE activation. Our results suggest that PIASy is an inhibitor of TRIF
      induced ISRE and NF-kappaB activation but not apoptosis.

PMID- 15251448
TI  - Characterization of H2O2-induced acute apoptosis in cultured neural
      stem/progenitor cells.
AB  - In the present study, we characterized hydrogen peroxide (H2O2)-induced cell
      apoptosis and related cell signaling pathways in cultured embryonic neural
      stem/progenitor cells (NS/PCs). Our data indicated that H2O2 induced acute cell
      apoptosis in NS/PC in concentration- and time-dependent manners and selectively,
      it transiently increased PI3K-Akt and Mek-Erk1/2 in a dose-dependent manner.
      Inhibition of PI3K-Akt with wortmannin, a PI3-K inhibitor, was found to
      significantly increase H2O2-induced acute apoptosis and dramatically decrease
      basal pGSK3beta levels. The level of pGSK3beta remained unchanged with H2O2
      exposure. We conclude that the transient activation of PI3K-Akt signaling delays
      the H2O2-induced acute apoptosis in cultured NS/PCs in part through maintaining
      the basal pGSK3beta level and activating other downstream effectors.

PMID- 15251449
TI  - Robust denoising of electrophoresis and mass spectrometry signals with minimum
      description length principle.
AB  - The need for high-throughput assays in molecular biology places increasing
      requirements on the applied signal processing and modelling methods. In order to
      be able to extract useful information from the measurements, the removal of
      undesirable signal characteristics such as random noise is required. This can be
      done in a quite elegant and efficient way by the minimum description length (MDL)
      principle, which treats and separates 'noise' from the useful information as that
      part in the data that cannot be compressed. In its current form the MDL denoising
      method assumes the Gaussian noise model but does not require any ad hoc parameter
      settings. It provides a basis for high-speed automated processing systems without
      requiring continual user interventions to validate the results as in the
      conventional signal processing methods. Our analysis of the denoising problem in
      mass spectrometry, capillary electrophoresis genotyping, and sequencing signals
      suggests that the MDL denoising method produces robust and intuitively appealing
      results sometimes even in situations where competing approaches perform poorly.

PMID- 15251450
TI  - Abeta production as consequence of cellular death of a human neuroblastoma
      overexpressing APP.
AB  - In human brain the Abeta peptide is produced mainly by neurons and the
      overexpression of amyloid precursor protein (APP) that involves an increase in
      Abeta secretion, has been observed in some areas of the Alzheimer's disease
      patients brain. We have generated two stably transfected human neuroblastoma
      lines which overexpress APP; both of them secreted Abeta and showed morphological
      changes and cell death with apoptotic program characteristics. Interestingly,
      coculture experiments with the untransfected human neuroblastoma cell line showed
      that the Abeta peptide was not responsible for the death in those cell lines;
      additionally, we indicate that upon cell death, Abeta peptide is secreted into
      cell medium.

PMID- 15251451
TI  - Structural analysis of the stalk subunit Vma5p of the yeast V-ATPase in solution.
AB  - Vma5p (subunit C) of the yeast V-ATPase was produced in Escherichia coli and
      purified to homogeneity. Analysis of secondary structure by circular dichroism
      spectroscopy showed that Vma5p comprises 64% alpha-helix and 17% beta-sheet
      content. The molecular mass of this subunit, determined by gel filtration
      analysis and small angle X-ray scattering (SAXS), was approximately 51+/-4 kDa,
      indicating a high hydration level of the protein in solution. The radius of
      gyration and the maximum size of Vma5p were determined to be 3.74+/-0.03 and
      12.5+/-0.1 nm, respectively. Using two independent ab initio approaches, the
      first low-resolution shape of the protein was determined. Vma5p is an elongated
      boot-shaped particle consisting of two distinct domains. Co-reconstitution of
      Vma5p to V1 without C from Manduca sexta resulted in a V1-Vma5p hybrid complex
      and a 20% increase in ATPase hydrolysis activity.

PMID- 15251452
TI  - CCL3, acting via the chemokine receptor CCR5, leads to independent activation of
      Janus kinase 2 (JAK2) and Gi proteins.
AB  - The interaction of the chemokine receptor, CCR5, expressed in recombinant cells,
      with different G proteins was investigated and CCR5 was found to interact with
      Gi, Go and Gq species. Interaction with Gi leads to G protein activation, whereas
      Gq does not seem to be activated. Additionally, CCR5 activation also leads to
      phosphorylation of Janus kinase 2 (JAK2). Activation of JAK2 is independent of Gi
      or Gq activation. Gi protein activation was not prevented by inhibition of JAK,
      showing that heterotrimeric G protein activation and activation of the JAK/signal
      transducer and activator of transcription (STAT) pathway are independent of each
      other.

PMID- 15251453
TI  - Calcium/calmodulin-dependent protein kinase I inhibits neuronal nitric-oxide
      synthase activity through serine 741 phosphorylation.
AB  - We demonstrate here that neuronal nitric-oxide synthase (nNOS) is phosphorylated
      and inhibited by a constitutively active form of Ca2+/calmodulin (CaM)-dependent
      protein kinase I (CaM-K I1-293). Substitution of Ser741 to Ala in nNOS blocked
      the phosphorylation and the inhibitory effect. Mimicking phosphorylation at
      Ser741 by Ser to Asp mutation resulted in decreased binding of and activation by
      CaM, since the mutation was within the CaM-binding domain. CaM-K I1-293 gave
      phosphorylation of nNOS at Ser741 in transfected cells, resulting in 60-70%
      inhibition of nNOS activity. Wild-type CaM-K I also did phosphorylate nNOS at
      Ser741 in transfected cells, but either CaM-K II or CaM-K IV did not. These
      results raise the possibility of a novel cross-talk between nNOS and CaM-K I
      through the phosphorylation of Ser741 on nNOS.

PMID- 15251454
TI  - Analysis of human tumour necrosis factor receptor 1 dominant-negative mutants
      reveals a major region controlling cell surface expression.
AB  - Tumour necrosis factor receptor 1 (TNFR1) plays a critical role in host defence
      and inflammation. We have identified a membrane proximal region (aa 218-324) of
      TNFR1 that restricts surface expression. This was prompted by comparing the
      dominant-negative properties of a C-terminal truncation of TNFR1 with a point
      mutant that prevents signalling. C-terminal truncation (aa 218-426) generates a
      better dominant-negative TNFR1 mutant than inactivation of the death domain by
      point mutation. The increased dominant-negative activity correlates with
      increased cell surface expression. The membrane proximal region is the most
      important region of the receptor for restricting expression.

PMID- 15251455
TI  - Direct interaction between BKCa potassium channel and microtubule-associated
      protein 1A.
AB  - The BKCa channel, a potassium channel that is allosterically activated by voltage
      and calcium, is expressed in both excitable and non-excitable cells. The channel
      plays an important role in regulating membrane excitability. The channel activity
      can be modulated by post-translational modifications such as phosphorylation.
      Recently, hippocampal BKCa channels were shown to be directly modulated by
      assembly/disassembly of the submembranous actin cytoskeleton. Here, we report
      that the BKCa channel physically interacts with the light chain of microtubule
      associated protein 1A (MAP1A). The light chain was isolated in a yeast two-hybrid
      screen of a human brain cDNA library. The specificity of the interaction was
      demonstrated in biochemical experiments utilizing GST fusion protein pulldown
      assays and reciprocal co-immunoprecipitations from rat brain. Furthermore,
      utilizing immunofluorescence, the BKCa channel and MAP1A co-localize in the
      Purkinje cell layer of the cerebellum. These studies identify a novel interaction
      between the C-terminal tail of the BKCa channel and the light chain of MAP1A,
      which enables channel association with and modulation by the cytoskeleton.

PMID- 15251456
TI  - A critical period requiring Rho proteins for cell cycle progression uncovered by
      reversible protein transduction in endothelial cells.
AB  - The time-specific requirement of Rho proteins for the S phase progression of
      vascular endothelial cells was determined by reversibly introducing inhibitor
      proteins with a cell-penetrating peptide. We found evidence of the reversibility
      of protein transduction. The removal of extracellular protein caused the
      transduced protein to decay in a manner sensitive to low temperatures. The time
      required for a 50% decay correlated with the protein size. The time-specific
      transduction of the inhibitor proteins uncovered a critical period requiring Rho
      proteins in the G1-S transition phase. Reversible protein transduction may thus
      be a powerful tool to investigate the time-specific role of signaling proteins.

PMID- 15251457
TI  - P-domain and lectin site are involved in the chaperone function of Saccharomyces
      cerevisiae calnexin homologue.
AB  - Cne1p, a calnexin homologue from Saccharomyces cerevisiae, has been shown to
      possess a conserved P-domain and lectin site as mammalian calnexin. The effect of
      P-domain and lectin site on the function of Cne1p was investigated in vitro using
      recombinant P-domain, P-domain deletion mutant of Cne1p, and lectin site mutant
      of Cne1ps (E181A and E398A) The binding of monoglucosylated oligosaccharide
      (G1M9) with Cne1p was clearly demonstrated using lectin site mutants. The P
      domain deletion mutant and the letcin site mutants partially decreased the
      ability to suppress the aggregation of citrate synthase (CS) and chicken egg yolk
      immunoglobulin at levels different from Cne1p. Furthermore, the P-domain deletion
      mutant and the lectin site mutants decreased the ability to enhance the refolding
      of CS. These results suggest that the cooperation between the P-domain and the
      lectin site are important for the complete function of Cne1p. Thus, we conclude
      that P-domain in cooperation with the lectin site of Cne1p functions as a
      chaperone.

PMID- 15251458
TI  - The intrinsic stability of the second intermediate following the dioxygen-bound
      form in the O2 reduction by cytochrome c oxidase.
AB  - Aeration of a two-electron reduced cytochrome c oxidase provides a species with
      two Raman bands at 804 and 356 cm(-1), identifying it as the second intermediate
      following the O2-bound species in the enzymatic O2 reduction process. It degrades
      directly to the fully oxidized form with a half-life time of 70 min at pH 8.0.
      The stability suggests an effective insulation for the active site in an
      extremely high oxidation state (Fe4+ with one oxidative equivalent nearby)
      against spontaneous electron leaks, which would dissipate proton motive force.
      The formation and degradation of the second intermediate are pH-dependent.

PMID- 15251459
TI  - The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin.
AB  - Hypoxia-inducible factor-1 (HIF) is regulated by oxygen-dependent prolyl
      hydroxylation. Of the three HIF prolyl hydroxylases (PHD1, 2 and 3) identified,
      PHD3 exhibits restricted substrate specificity in vitro and is induced in
      different cell types by diverse stimuli. PHD3 may therefore provide an interface
      between oxygen sensing and other signalling pathways. We have used co
      purification and mass spectrometry to identify proteins that interact with PHD3.
      The cytosolic chaperonin TRiC was found to copurify with PHD3 in extracts from
      several cell types. Our results indicate that PHD3 is a TRiC substrate, providing
      another step at which PHD3 activity may be regulated.

PMID- 15251461
TI  - Biophysical characterization of natural and mutant fluorescent proteins cloned
      from zooxanthellate corals.
AB  - Two novel colored fluorescent proteins were cloned and biophysically
      characterized from zooxanthellate corals (Anthozoa). A cyan fluorescent protein
      derived from the coral Montastrea cavernosa (mcCFP) is a trimeric complex with
      strong blue-shifted excitation and emission maxima at 432 and 477 nm,
      respectively. The native complex has a fluorescence lifetime of 2.66+/-0.01 ns
      and an inferred absolute quantum yield of 0.385. The spectroscopic properties of
      a green fluorescent protein cloned from Meandrina meandrites (mmGFP) resemble the
      commercially available GFP derived originally from the hydrozoan Aequorea
      victoria (avGFP). mmGFP is a monomeric protein with an excitation maximum at 398
      nm and an emission maximum at 505 nm, a fluorescence lifetime of 3.10+/-0.01 ns
      and an absolute quantum yield of 0.645. Sequence homology with avGFP and the red
      fluorescent protein (DsRed) indicates that the proteins adopt the classic beta
      barrel configuration with 11 beta-strands. The three amino acid residues that
      comprise the chromophore are QYG for mcCFP and TYG for mmGFP, compared with SYG
      for avGFP. A single point mutation, Ser-110 to Asn, was introduced into mmGFP by
      random mutagenesis. Denaturation and refolding experiments showed that the mutant
      has reduced aggregation, increased solubility and more efficient refolding
      relative to the wild type. Time-resolved emission lifetimes and anisotropies
      suggest that the electronic structure of the chromophore is highly dependent on
      the protonation state of adjoining residues.

PMID- 15251460
TI  - Temperature and cryoprotectant influence secondary quinone binding position in
      bacterial reaction centers.
AB  - We have determined the first de novo position of the secondary quinone QB in the
      Rhodobacter sphaeroides reaction center (RC) using phases derived by the single
      wavelength anomalous dispersion method from crystals with selenomethionine
      substitution. We found that in frozen RC crystals, QB occupies primarily the
      proximal binding site. In contrast, our room temperature structure showed that QB
      is largely in the distal position. Both data sets were collected in dark-adapted
      conditions. We estimate that the occupancy of the QB site is 80% with a proximal:
      distal ratio of 4:1 in frozen RC crystals. We could not separate the effect of
      freezing from the effect of the cryoprotectants ethylene glycol or glycerol.
      These results could have far-reaching implications in structure/function studies
      of electron transfer in the acceptor quinone complex because the above are the
      most commonly used cryoprotectants in spectroscopic experiments.

PMID- 15251462
TI  - 1-Hydroxy monocyclic carotenoid 3,4-dehydrogenase from a marine bacterium that
      produces myxol.
AB  - A crtD (1-HO carotenoid 3,4-dehydrogenase gene) homolog from marine bacterium
      strain P99-3 included in the gene cluster for the biosynthesis of myxol (3',4'
      didehydro-1',2'-dihydro-beta, psi-carotene-3,1',2'-triol) was functionally
      identified. The P99-3 CrtD was phylogenetically distant from the other CrtDs. A
      catalytic feature was its high activity for the monocyclic carotenoid conversion:
      1'-HO-torulene (3',4'-didehydro-1',2'-dihydro- beta, psi-caroten-1'-ol) was
      prominently formed from 1'-HO-gamma-carotene (1',2'-dihydro-beta, psi-caroten-1'
      ol) in Escherichia coli with P99-3 CrtD, indicating that this enzyme has been
      highly adapted to myxol biosynthesis. This unique type of crtD is a valuable tool
      for obtaining 1'-HO-3',4'-didehydro monocyclic carotenoids in a heterologous
      carotenoid production system.

PMID- 15251463
TI  - Aldose reductase regulates TNF-alpha-induced cell signaling and apoptosis in
      vascular endothelial cells.
AB  - In this study, we examined the role of aldose reductase (AR) in regulating the
      cytotoxic effects of TNF-alpha on human umbilical vein endothelial cells.
      Inhibition of AR by sorbinil or tolrestat prevented TNF-alpha-induced increase in
      Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA
      binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in
      cells stimulated by TNF-alpha. Exposure to TNF-alpha also induced apoptotic cell
      death, which was attenuated by AR inhibition or antisense ablation. These
      observations suggest that AR is a critical regulator of TNF-alpha-induced
      apoptotic signaling in endothelial cells.

PMID- 15251464
TI  - Suppression of bcr-abl synthesis by siRNAs or tyrosine kinase activity by Glivec
      alters different oncogenes, apoptotic/antiapoptotic genes and cell proliferation
      factors (microarray study).
AB  - Short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) were designed to
      target bcr-abl mRNA in chronic myelogenous leukemia. The ds/siRNAs were
      transfected into bcr-abl-positive K-562 (derived from blast crisis chronic
      myelogenous leukemia), using lipofectamine. Penetrating of ds/siRNAs into the
      cells was detected by fluorescent confocal microscopy, using fluorescein-labeled
      ds/siRNAs. The cells were treated with mix of three siRNA sequences (3 x 60 nM)
      during 6 days with three repetitive transfections. The siRNA-treatment was
      accompanied with significant reduction of bcr-abl mRNA, p210, protein tyrosine
      kinase activity and cell proliferation index. Treatment of cells with Glivec
      (during 8 days with four repetitive doses, 180 nM single dose) resulted in
      analogous reduction of cell proliferation activity, stronger suppression of
      protein tyrosine kinase activity, and very low reduction of p210. siRNA-mix and
      Glivec did not affect significantly the viability of normal lymphocytes.
      Microarray analysis of siRNA- and Glivec-treated K-562 cells demonstrated that
      both pathways of bcr-abl suppression were accompanied with overexpression and
      suppression of many different oncogenes, apoptotic/antiapoptotic and cell
      proliferation factors. The following genes of interest were found to decrease in
      relatively equal degree in both siRNA- and Glivec-treated cells: Bcd orf1 and
      orf2 proto-oncogene, chromatin-specific transcription elongation factor FACT 140
      kDa subunit mRNA, gene encoding splicing factor SF1, and mRNA for Tec protein
      tyrosine kinase. siRNA-mix and Glivec provoked overexpression of the following
      common genes: c-jun proto-oncogene, protein kinase C-alpha, pvt-1 oncogene
      homologue (myc activator), interleukin-6, 1-8D gene from interferon-inducible
      gene family, tumor necrosis factor receptor superfamily (10b), and STAT-induced
      STAT inhibitor.

PMID- 15251465
TI  - Thymidylate synthase inhibition triggers glucose-dependent apoptosis in p53
      negative leukemic cells.
AB  - Chemotherapeutic drugs that inhibit the synthesis of DNA precursor thymidine
      triphosphate cause apoptosis, although the mechanism underlying this process
      remains rather unknown. Here, we describe thymineless death of human myeloid
      leukemia U937 cells treated with the thymidylate-synthase inhibitor 5'-fluoro- 2'
      deoxyuridine (FUdR). This apoptotic process was shown to be independent of p53,
      reactive oxygen species generation and CD95 activation. Caspases were activated
      downstream of cytochrome c but upstream of mitochondrial depolarization.
      Furthermore, FUdR-induced apoptosis required the presence of glucose in the
      culture medium at a step upstream of the release of cytochrome c from
      mitochondria.

PMID- 15251466
TI  - The presence of a high-Km hexokinase activity in dog, but not in boar, sperm.
AB  - The presence of a high-Km hexokinase activity was tested in both dog and boar
      spermatozoa. Hexokinase kinetics from dog extracts showed the presence of a
      specific activity (dog-sperm glucokinase-like protein, DSGLP), in the range of
      glucose concentrations of 4-10 mM, whereas boar sperm did not show any DSGLP
      activity. Furthermore, dog-sperm cells, but not those of boar, showed the
      presence of a protein which specifically reacted against a rat-liver anti
      glucokinase antibody. This protein also had a molecular weight equal to that
      observed in rat-liver extracts, suggesting a close similarity between both the
      proteins. This glucokinase-like protein was distributed in the peri- and post
      acrosomal zones of the head, and the midpiece and principal piece of tail of dog
      spermatozoa. These results indicate that dog spermatozoa have functional high-Km
      hexokinase activity, which could contribute to a very fine regulation of their
      hexose metabolism. This strict regulation could ultimately be very important in
      optimizing dog-sperm function along its life-time.

PMID- 15251467
TI  - Characterization of an oxaloacetate decarboxylase that belongs to the malic
      enzyme family.
AB  - The citM gene from Lactococcus lactis CRL264 was demonstrated to encode for an
      oxaloacetate decarboxylase. The enzyme exhibits high levels of similarity to
      malic enzymes (MEs) from other organisms. CitM was expressed in Escherichia coli,
      purified and its oxaloacetate decarboxylase activity was demonstrated by
      biochemical and genetic studies. The highest oxaloacetate decarboxylation
      activity was found at low pH in the presence of manganese, and the Km value for
      oxaloacetate was 0.52+/-0.03 mM. However, no malic activity was found for this
      enzyme. Our studies clearly show a new group of oxaloacetate decarboxylases
      associated with the citrate fermentation pathway in gram-positive bacteria.
      Furthermore, the essential catalytic residues were found to be conserved in all
      members of the ME family, suggesting a common mechanism for oxaloacetate
      decarboxylation.

PMID- 15251468
TI  - Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte
      stimulating hormone.
AB  - Prostaglandins are potent mediators of the inflammatory response and are also
      involved in cancer development. In this study, we show that human melanocytes and
      FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have
      the capability to produce prostaglandins. The FM55 cells produced predominantly
      PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly
      PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha
      MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the
      effect of the pro-inflammatory cytokine TNF-alpha in the former. These results
      indicate that melanocytes produce prostaglandins and that alpha-MSH, by
      inhibiting this response, may play an important role in regulating inflammatory
      responses in the skin.

PMID- 15251469
TI  - Prognostic value of suppressed thyrotropin level and positive thyrotropin
      receptor antibody activity in Graves' disease with long-lasting clinical
      remission.
AB  - OBJECTIVE: To determine the prognostic value of suppressed thyrotropin (TSH)
      level and positive TSH-receptor antibodies (TSH-R Ab) in patients with Graves'
      disease who have long-lasting clinical remission. METHODS: We retrospectively
      studied patients with Graves' disease who underwent follow-up for a mean of 55
      months after the withdrawal of antithyroid drug treatment. Study patients were 84
      consecutive subjects in clinical remission, with normal serum free thyroxine
      (FT(4)) and free triiodothyronine (FT(3)) levels, regardless of serum TSH levels,
      a mean of 35 months (range, 6 to 135) after discontinuation of carbimazole
      therapy. Eighty-seven euthyroid subjects were used as control study participants.
      All subjects had serum determinations of FT(4) and FT(3) (radioimmunoassay), TSH
      (highly sensitive immunoradiometric method), TSH-R Ab (radioreceptor assay), and
      microsomal antibodies (M Ab, passive hemagglutination method). RESULTS: In the
      study patients, serum TSH was suppressed (</=0.10 mU/L) in 13 cases (15%), TSH-R
      Ab were positive (>/=15%) in 11 cases (13%), and M Ab were positive (>/=1:100) in
      54 cases (64%). Simultaneous suppressed TSH and positive TSH-R Ab levels were
      present in six patients. During the follow-up, 11 patients had a relapse,
      demonstrated by above-normal values for serum FT(4) and FT(3) in association with
      clinical symptoms of hyperthyroidism. Five of them had a previously suppressed
      TSH level, three had a positive TSH-R Ab level, and six had a positive M Ab
      titer. Relapse was significantly more likely in patients with a previously
      suppressed TSH level (P<0.02) but not in patients with a previously positive TSH
      R Ab level or positive M Ab titer. CONCLUSION: Patients with Graves' disease and
      long-lasting clinical remission after discontinuation of carbimazole therapy may
      have a suppressed TSH level, a positive TSH-R Ab level, or a positive M Ab titer
      (or some combination of these findings). Although positive TSH-R Ab and M Ab have
      no significant prognostic value, a suppressed TSH level is indicative of
      subclinical hyperthyroidism and higher risk of relapse.

PMID- 15251470
TI  - Central and peripheral neural responses in acromegaly.
AB  - OBJECTIVE: To assess the function of the central and peripheral nervous systems
      in patients with untreated acromegaly. METHODS: We recorded the somatosensory
      evoked potentials (SSEPs) and brain stem auditory evoked potentials (BAEPs) in 10
      patients with untreated acromegaly of brief duration and in 20 age- and sex
      matched healthy control subjects to evaluate the function of the central nervous
      system and at least the median and tibial components of the peripheral nerves.
      Electrophysiologic studies were done at the time of diagnosis and before the
      initiation of any treatment for acromegaly. We also studied the distal motor
      latency, nerve conduction velocity, compound muscle action potentials, and F
      response in the peroneal nerve; the sensory nerve conduction velocity and sensory
      potential amplitude were measured in the sural nerve. RESULTS: The mean duration
      of acromegaly (expressed as time elapsed since patients first recognized signs or
      symptoms) was 2.4 years. The N(9) and N(13) latencies in median SSEPs and the
      N(22) latency in tibial SSEPs were significantly prolonged in patients with
      acromegaly in comparison with the control group; however, central nervous system
      components of SSEPs and all components of BAEPs were normal. We also noted
      abnormalities in peroneal motor and sural sensory nerves. No correlation was
      found between the neurophysiologic data and the basal growth hormone level, the
      fasting blood glucose level, or the duration of disease. CONCLUSION: Our results
      suggest that peripheral, but not central, nervous system involvement exists in
      patients with untreated acromegaly of short duration.

PMID- 15251471
TI  - Intermittent hypercortisolism: a disorder strikingly prevalent after hypophysial
      surgical procedures.
AB  - OBJECTIVE: To determine the frequency of intermittent hypercortisolism in a
      consecutive series of patients with Cushing's disease who underwent hypophysial
      surgical treatment. METHODS: Thirty-three patients with hypercortisolism of
      central origin underwent follow-up at approximately annual intervals for
      prolonged periods after a transsphenoidal pituitary surgical procedure. Clinical
      evaluation was done, and urinary steroid measurements, as well as dexamethasone
      suppression tests in some patients, were performed. RESULTS: Frequently normal
      but intermittently increased urinary 17-hydroxycorticosteroid or cortisol
      excretion (or both) was found in six patients postoperatively, associated with
      intermittently severe hypertension, headaches, and weakness in only one patient.
      In a seventh patient, intermittently excessive cortisol excretion was clearly
      evident preoperatively. CONCLUSION: Because corticoid excretion was variable
      preoperatively in three of the seven study patients, we conclude that
      intermittent hypercortisolism is commoner than previous evidence has shown,
      constitutes an extremely difficult diagnostic problem, and did not result from
      but failed to be cured by pituitary surgical treatment in 6 of 33 patients (18%).
      The findings emphasize the need for regular follow-up for several years in all
      patients with Cushing's syndrome who have undergone a hypophysial surgical
      procedure. Variable consistency of follow-up might partly explain the wide
      discrepancies between reports of 80 to 90% and 40 to 60% cure rates after a
      single hypophysial adenomectomy.

PMID- 15251473
TI  - Spurious hypophosphatemia associated with multiple myeloma.
AB  - OBJECTIVE: To report on the phenomenon of spurious hypophosphatemia associated
      with multiple myeloma. METHODS: A case report is presented, and the pertinent
      published literature is reviewed. The mechanisms by which multiple myeloma can
      cause both true and false hypophosphatemia are discussed, as are methods by which
      the important distinction between these conditions can be made. RESULTS: At the
      time of surgical treatment of a hip fracture, an 80-year-old man with a history
      of multiple myeloma was found to have hypophosphatemia. Despite intravenous
      administration of large amounts of phosphate, the low phosphate values persisted.
      Only when a blood sample was submitted to another laboratory that used a
      different technique for determining phosphate was a normal phosphate level
      reported. CONCLUSION: In patients with multiple myeloma, the myeloma protein can
      cause biochemical interference with certain phosphate assays, which could lead to
      false results. This phenomenon should be considered in such patients in order to
      avoid inappropriate and potentially dangerous phosphate replacement therapy.

PMID- 15251472
TI  - The ovine corticotropin-releasing hormone stimulation test in the differential
      diagnosis of adrenocorticotropic hormone-dependent cushing's syndrome.
AB  - OBJECTIVE: To determine the efficacy of the ovine corticotropin-releasing hormone
      (oCRH) stimulation test in distinguishing between adrenocorticotropic hormone
      (ACTH)-dependent types of Cushing's syndrome. METHODS: The cortisol and ACTH
      responses to intravenously administered oCRH were determined in 64 patients with
      pituitary-dependent Cushing's syndrome and 13 patients with ectopic ACTH
      production. RESULTS: Of the 64 patients with pituitary-dependent Cushing's
      syndrome, 57 (89%) had a positive ACTH response to administration of oCRH (an
      increase of 50% or more above baseline), and 56 (88%) had a positive cortisol
      response (an increase of 20% or more above baseline). One patient with an ectopic
      ACTH-secreting tumor had a false-positive cortisol response to administration of
      oCRH. Two patients with ectopic ACTH-secreting tumors had false-positive
      responses to both ACTH and cortisol after oCRH was administered. Because both
      these patients did not have hypercortisolemia at the time of testing, they were
      excluded from the statistical analysis. When analyzed on the basis of ACTH
      response alone, oCRH testing yielded a diagnostic sensitivity and specificity for
      the diagnosis of pituitary-dependent hypercortisolism of 89% and 100%,
      respectively. The positive predictive value was 100%, and the negative predictive
      value was 61%. CONCLUSION: oCRH testing distinguished between the ectopic ACTH
      syndrome and pituitary-dependent hyper-cortisolism in most cases. Therefore, this
      test is a useful procedure in the diagnostic evaluation of ACTH-dependent forms
      of Cushing's syndrome.

PMID- 15251474
TI  - Reversible avascular necrosis of the femoral head in tumor-induced osteomalacia.
AB  - OBJECTIVE: To document the course and reversal of avascular necrosis of the
      femoral heads (ANFH) in a 27-year-old woman with tumor-induced osteomalacia
      (TIO). METHODS: We describe clinical, biochemical, and magnetic resonance imaging
      changes in a patient who sought medical assistance because of pain in her back,
      hips, and knees and an enlarging mass on her right thigh. RESULTS: The patient
      proved to have TIO, an unusual condition characterized by humorally controlled
      renal phosphate wasting, low to undetectable levels of 1,25-dihydroxyvitamin
      D(3), and osteomalacia. Eleven months after removal of a small spindle cell tumor
      of the right thigh and without other treatment, complete clinical and biochemical
      remission was observed, and the magnetic resonance images revealed resolution of
      the ANFH. CONCLUSION: Prompt treatment of ANFH in TIO can lead to complete
      radiologic and clinical remission.

PMID- 15251475
TI  - Cushing'S syndrome attributable to topical use of lotrisone.
AB  - OBJECTIVE: To emphasize the potentially devastating consequences of topical
      application of corticosteroids. METHODS: A case report is presented of a
      previously healthy 38-year-old woman in whom florid Cushing's syndrome developed
      after prolonged use of Lotrisone. RESULTS: Four years of continuous topical
      administration of Lotrisone, a combination antifungal-corticosteroid product, led
      to the development of Cushing's syndrome. The cream had been applied to less than
      10% of the total body surface area without use of occlusive dressings, and the
      patient had no evidence of liver dysfunction or systemic skin disorder.
      Laboratory studies revealed an unmeasurable corticotropin level, suppressed or
      unmeasurable cortisol levels, and suppressed or low-normal 24-hour urine
      collection values for 17-hydroxy-steroids, 17-ketosteroids, and urinary free
      cortisol, all of which confirm suppression of the hypothalamic-pituitary-adrenal
      axis. CONCLUSION: (1) Betamethasone dipropionate can lead to the development of
      Cushing's syndrome, even in the absence of enhancing factors. (2) Combination
      medications can lead to the unintentional use of component agents. (3)
      Availability of potent corticosteroids as over-the-counter medications allows for
      inappropriate duration of therapy and inadequate medical supervision.

PMID- 15251476
TI  - Importance of control in type II diabetes mellitus.
AB  - OBJECTIVE: To determine the effect of maintenance of control of type II diabetes
      mellitus on the occurrence of complications. METHODS: Various published studies
      of populations of patients with diabetes are reviewed, and their results in terms
      of diabetic control and development of retinopathy, nephropathy, neuropathy, and
      macrovascular disease are summarized. RESULTS: Maintenance of near-euglycemia
      reduced the risk of worsening diabetic retinopathy; proliferative retinopathy
      developed in few patients with well-controlled diabetes. Similarly, worsening
      proteinuria was more common in patients with fair and poor control of diabetes in
      comparison with those who were able to maintain good control of diabetes.
      Furthermore, patients with poor diabetic control experienced a faster
      deterioration of peripheral neurologic function than did the patients with well
      controlled diabetes. In five prospective studies of a total of 2,471 patients
      with type II diabetes, stricter control of diabetes was associated with fewer
      cardiovascular events and deaths. CONCLUSION: Overwhelming evidence from
      published prospective studies indicates that the complications often associated
      with type II diabetes can be minimized or delayed by maintaining good control of
      the disease.

PMID- 15251477
TI  - Thyroid ultrasonography--a review.
AB  - OBJECTIVE: To review the major applications of ultrasonography in studies of the
      thyroid gland by clinical endocrinologists. METHODS: The techniques for
      performance of thyroid ultrasonography and ultrasound-guided fine-needle
      aspiration biopsy are outlined, and the settings for their use are discussed.
      Characteristic findings and limitations are described. RESULTS: In two situations
      -the assessment of thyroid nodules and the postoperative follow-up of thyroid
      cancer--ultrasonography and ultrasound-guided fine-needle aspiration biopsy have
      proved to be clinically useful when used in combination. On ultrasonography, a
      hyperechoic nodule with a sharp "halo" is associated with a low risk of
      malignancy and a hypoechoic nodule with microcalcifications is associated with a
      high risk of a malignant lesion, but performance of a biopsy is recommended.
      Ultrasonography coupled with ultrasound-guided fine-needle aspiration biopsy can
      detect >90% of recurrent cases of thyroid carcinoma. In general, normal lymph
      nodes appear flattened on ultrasonography, whereas malignant nodes appear more
      rounded or bulging. CONCLUSION: Thyroid ultrasonography and fine-needle
      aspiration biopsy are complementary diagnostic procedures in the evaluation of
      thyroid nodules and for detection of recurrent or metastatic thyroid carcinoma.

PMID- 15251478
TI  - Diabetes education programs and the endocrinologist.
AB  - In the past, control of diabetes was considered important, but studies had not
      substantiated the effect of high-quality care on the outcome for patients with
      diabetes. Recently, however, published results of the Diabetes Control and
      Complications Trial indicated that optimal control of diabetes minimized the
      associated complications. As a consequence, educational efforts have focused on
      informing and encouraging patients with diabetes to help achieve and maintain the
      best possible medical care. This situation has created a market for products and
      services to assist patients with diabetes, and many nonphysicians have promoted
      their products without actual participation in a team effort to improve outcomes
      for patients with diabetes. Clinical endocrinologists, who are experts in the
      management of diabetes, should assume a leadership role on the diabetes-care team
      and should not relinquish this responsibility to those who are less qualified to
      provide care for the growing number of patients with diabetes who seek optimally
      effective treatment.

PMID- 15251479
TI  - Outcome of metformin-facilitated reinitiation of oral diabetic therapy in insulin
      treated patients with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To test the feasibility of reimplementation of oral diabetic therapy
      in insulin-treated patients with non-insulin-dependent diabetes mellitus (NIDDM)
      and to determine the characteristics of patients in whom such conversion was
      successful. METHODS: We attempted reinitiation of combination oral therapy with
      metformin and a sulfonylurea in 55 consecutive C-peptide-positive patients who
      had had NIDDM for less than 30 years and had received insulin therapy for less
      than 10 years. RESULTS: Reinitiation of oral therapy was successful in 42
      patients and unsuccessful in 13. Reinitiation of oral therapy was unsuccessful
      because of lack of diabetic control in nine patients and gastrointestinal side
      effects in four patients. The successful group had a lower insulin requirement (P
      = 0.004), a shorter duration of insulin therapy (P = 0.013), and a lower body
      mass index (P = 0.014). Baseline glycosylated hemoglobin, C-peptide level, age,
      and duration of diabetes were not significant predictive factors. Glycosylated
      hemoglobin levels were significantly lower (mean, 1.3%; P = 0.0001) after
      successful reinitiation of oral therapy in comparison with before. Both groups of
      patients (those with successful and those with unsuccessful conversion to oral
      therapy) lost weight. CONCLUSION: The group of patients with NIDDM in whom
      reinitiation of combination oral therapy is most likely to be successful are
      those with a shorter duration of insulin therapy, lower insulin requirements, and
      lower body mass index. Successful conversion to oral diabetic therapy
      significantly decreases the glycosylated hemoglobin level.

PMID- 15251480
TI  - Exacerbation of warfarin-induced anticoagulation by hyperthyroidism.
AB  - OBJECTIVE: To alert clinicians to the potential interaction between warfarin and
      hyperthyroidism. METHODS: We present two case reports and compare findings with
      those in a control population of patients with hyperthyroidism who were not
      receiving anticoagulant therapy. RESULTS: In two patients, severe coagulopathy
      was precipitated by the interaction of warfarin and increased thyroid hormone
      levels. In both cases, the patients also demonstrated resistance to vitamin K
      therapy, which persisted for several days. We also studied five control patients
      with hyperthyroidism who were not taking anticoagulant drugs; no effect of
      thyroid hormone on the plasma levels of vitamin K-dependent clotting factors was
      noted. One of our patients with hyperthyroidism who was taking warfarin had
      levels of warfarin in the serum that were 5 times the therapeutic range; this
      finding suggests that the protein binding or absorption of warfarin may be
      altered in such patients. CONCLUSION: Multiple factors may contribute to the
      enhanced effect of warfarin seen in patients with hyperthyroidism, including
      altered metabolism of vitamin K-dependent clotting factors, altered metabolism of
      warfarin, or decreased protein binding of the drug. Patients with hyperthyroidism
      should be given lower doses of warfarin to avoid severe coagulopathy.

PMID- 15251481
TI  - Gynecomastia as the initial manifestation of hyperthyroidism.
AB  - OBJECTIVE: To present two new cases of gynecomastia as the initial manifestation
      of hyperthyroidism. METHODS: We describe detailed case reports of two men with
      breast enlargement who were found to have hyperthyroidism, and we review the
      related literature. RESULTS: Two men sought medical assistance because of
      unilateral tender gynecomastia. In one of these patients, thyroid, gonadal, and
      prostate examinations showed normal findings at the time of initial assessment,
      and symptoms of hyperthyroidism developed later. In our other patient with
      gynecomastia, other symptoms of hyperthyroidism--for example, nervousness,
      irritability, palpitations, and fatigue--had been present for a prolonged period
      but had been considered "normal" by the patient. In both patients, the
      hyperthyroidism was treated with radioiodine. Breast pain disappeared in both
      patients, and breast enlargement disappeared in one patient and was decreased in
      the other patient after euthyroidism was achieved. Review of the literature
      disclosed only two similar cases. CONCLUSION: Because of the rarity of
      gynecomastia as the initial symptom of hyperthyroidism, we believe that thyroid
      function tests are not indicated in the workup of patients whose major complaint
      is gynecomastia.

PMID- 15251482
TI  - Magnetic resonance imaging in sheehan's syndrome: case report and literature
      review of imaging studies.
AB  - OBJECTIVE: To present the first documentation of pituitary atrophy on magnetic
      resonance imaging (MRI) in a patient with Sheehan's syndrome and review the
      published radiologic findings in this syndrome. METHODS: We describe the clinical
      and laboratory findings in a young woman with Sheehan's syndrome, provide the MRI
      results, and discuss the previously published radiologic studies of this
      syndrome. RESULTS: A 31-year-old woman, who was examined 11 months after severe
      postpartum hemorrhage, had clinical and biochemical findings consistent with
      Sheehan's syndrome (loss of axillary hair, amenorrhea, and impaired pituitary
      reserve for luteinizing hormone, follicle-stimulating hormone, thyrotropin,
      growth hormone, and corticotropin). MRI showed a partially empty sella in
      conjunction with invagination of the optic chiasm anteriorly into the pituitary
      fossa. CONCLUSION: Because of its greater spatial resolution, higher signal-to
      noise ratio, and potential for multiplanar images, MRI can provide more precise
      and detailed findings than other radiologic studies and can facilitate diagnosis
      of Sheehan's syndrome.

PMID- 15251483
TI  - Pseudohypohyperparathyroidism: a case study of differential resistance to
      parathyroid hormone.
AB  - OBJECTIVE: To present a rare case of a combination of hyperparathyroidism and
      hypoparathyroidism in a 30-year-old woman. METHODS: We review the laboratory,
      radiographic, and pathologic findings in a healthy-appearing woman who sustained
      a patellar fracture after a simple fall at home. RESULTS: Our patient had
      features of hypoparathyroidism--that is, tetanic crises and hypocalcemia--and
      also hyperparathyroidism--fracture of the patella, multiple bone cysts, and
      confirmed osteitis fibrosa cystica on bone biopsy specimens. These features were
      associated with a high serum level of intact parathyroid hormone (PTH) and
      parathyroid hyperplasia. A lack of response of nephrogenic cyclic adenosine
      monophosphate (cAMP) to PTH stimulation was observed along with subnormal serum
      cAMP responses. In contrast, urine phosphate excretion increased after
      administration of PTH. CONCLUSION: These results demonstrate a state of renal PTH
      resistance in a patient with osteitis fibrosa cystica.

PMID- 15251484
TI  - Pheochromocytoma.
AB  - OBJECTIVE: To characterize the symptoms associated with pheochromocytoma and
      discuss the diagnosis and management of this tumor. METHODS: We review the
      clinical manifestations in patients with pheochromocytoma, the biochemical and
      imaging studies recommended for diagnosis and localization of the tumor, and the
      available strategies for treatment. RESULTS: Pheochromocytoma is a tumor of
      chromaffin cells that originates in either the adrenal medulla or the extra
      adrenal sympathetic tissues. It is usually unilateral and benign. Frequent
      initial symptoms include headache, sweating, and palpitations, with or without
      increased blood pressure. In many patients, hypertension is accelerated during a
      paroxysm. Pheochromocytoma may also occur as a part of multiple endocrine
      neoplasia type IIA and B. Several common syndromes, such as panic disorders and
      hyperthyroidism, may mimic pheochromocytoma; however, pheochromocytoma should be
      suspected in the presence of hypertension, tachycardia, and throbbing headache,
      especially occurring as paroxysmal episodes. The physiologic diagnosis of
      pheochromocytoma is established by biochemical tests of levels of plasma and
      urinary catecholamines or their metabolites (or both). In most patients, anatomic
      localization is achieved with computed tomography or magnetic resonance imaging,
      metaiodobenzylguanidine scintigraphy, labeled somatostatin scans, or positron
      emission tomography. The management preferentially includes surgical removal of
      the pheochromocytoma after preparation with appropriate medical therapy to avoid
      hypertensive crisis during the perioperative period. Patients with
      contraindications to a major surgical procedure or with malignant
      pheochromocytoma and metastatic disease, however, may be treated with multiple
      drugs--for example, alpha- and beta-adrenergic blockers and direct vasodilators
      to neutralize the effects of high levels of circulating catecholamines and alpha
      methyl-metatyrosine to inhibit catecholamine synthesis. CONCLUSION: The presence
      of suggestive clinical features in patients with hypertension should prompt
      clinicians to undertake appropriate diagnostic testing because surgical resection
      of a pheochromocytoma will yield a cure in many cases.

PMID- 15251485
TI  - Nonpharmacologic approaches to therapy for hypertension.
AB  - OBJECTIVE: To provide an overview of nondrug therapeutic modalities for
      management of hypertension. METHODS: We review four strategies that involve
      lifestyle changes--weight reduction, moderation of sodium intake, physical
      activity, and moderation of alcohol consumption--that can potentially have a
      blood pressure-lowering effect. RESULTS: Several clinical trials have shown that
      a weight loss of 10 to 20% will significantly decrease blood pressure. An average
      of 1 to 2 mm Hg reduction in blood pressure may occur per kilogram of weight
      lost. Although sodium restriction has less effect on blood pressure than does
      weight reduction, a decrease in sodium intake to <100 mmol/day can yield a mean
      blood pressure reduction of 3 to 5 mm Hg systolic and 2 to 3 mm Hg diastolic.
      Exercise regimens have demonstrated convincing antihypertensive effects. In
      recent randomized studies, the average reduction in blood pressure ranged from 5
      to 15 mm Hg for systolic measurements and 5 to 10 mm Hg for diastolic readings.
      Alcohol consumption has been shown to have one of the strongest associations with
      blood pressure among the potentially modifiable risk factors for hypertension. An
      average of 1 mm Hg decrease in blood pressure has been noted per one drink/day
      reduction in consumption. CONCLUSION: Lifestyle changes that can decrease blood
      pressure are important because they may not only eliminate the need for drug
      treatment but also decrease other cardiovascular risk factors.

PMID- 15251486
TI  - The endocrinologist as the focus in a multidisciplinary approach to management of
      erectile dysfunction.
AB  - OBJECTIVE: To present an approach to the complete but cost-effective office
      evaluation and treatment of erectile dysfunction. METHODS: The numerous medical,
      hormonal, and psychologic causes of erectile dysfunction are reviewed, and the
      various treatment strategies are outlined. RESULTS: Erectile dysfunction, which
      might also include libido and ejaculatory disturbances, is the most frequently
      encountered type of sexual dysfunction seen in office practice. Before 1960, the
      assessment of this disorder was dominated by psychiatrists; later, urologists
      assumed a role. More recently, physicians in internal medicine have become
      involved in the management of this problem. Diabetes mellitus, hypertension, and
      tobacco abuse are the three most common causes of erectile dysfunction in men
      older than 50 years of age. In addition to optimizing the management of diabetes,
      the endocrinologist can treat other endocrine problems associated with erectile
      dysfunction. CONCLUSION: A multidisciplinary approach to the evaluation and
      treatment of erectile dysfunction is logical, and the endocrinologist--because of
      an extensive background in internal medicine and expertise in hormonal diagnosis
      and treatment--should be the focal point of this diagnostic and therapeutic team.

PMID- 15251487
TI  - Has fine-needle aspiration biopsy changed thyroid practice?
AB  - OBJECTIVE: To assess the influence of fine-needle aspiration (FNA) biopsy on the
      management of nodular thyroid disease. METHODS: We retrospectively evaluated the
      effect of the availability of FNA biopsy on thyroid surgical practice at our
      institution by comparing the data for two study periods--1975-1976 (before the
      introduction of FNA) and 1985-1986 (5 years after its introduction). RESULTS: The
      study inclusion criteria were fulfilled by 1,451 patients. In 1975-1976, 938
      patients had thyroid operations at our institution. FNA biopsy was introduced
      into our practice in 1980. In 1985-1986, 513 patients underwent a thyroid
      surgical procedure. Before the FNA era, the frequency of carcinoma in patients
      selected for thyroidectomy was 18%, whereas after FNA became available, it
      increased to 25% (P< 0.0001). When patients were selected for surgical treatment
      because of either "suspicious" or malignant cytologic results, the yield of
      carcinoma increased to 40%. CONCLUSION: These data suggest that FNA biopsy has
      improved selectivity for operation in patients with nodular thyroid disease and
      has reduced the number of patients who undergo thyroidectomy for benign disease.
      The result is an increasing yield of malignant lesions found at surgical
      intervention. FNA biopsy has had a substantial cost-saving effect on thyroid
      practice.

PMID- 15251488
TI  - Acute suppurative thyroiditis in a primary intrathoracic goiter.
AB  - OBJECTIVE: To describe a case of acute suppurative thyroiditis and focal abscess
      formation in a patient with a primary intrathoracic goiter. METHODS: We summarize
      the initial clinical manifestations, the pathologic findings, and the surgical
      treatment of a woman with an enlarging mediastinal mass. RESULTS: A 41-year-old
      woman had a fever and a sudden increase in severity of compressive symptoms after
      a remote urinary tract infection. Smears from an intraoperative fine-needle
      aspiration biopsy showed necrotic debris, polymorphonuclear leukocytes,
      hemosiderin-laden macrophages, and degenerated follicular epithelial cells. Urine
      and tissue cultures grew Escherichia coli. The patient underwent resection of an
      800-g primary intrathoracic goiter with associated degeneration, necrosis,
      hemorrhage, and abscess formation. CONCLUSION: To our knowledge, this is the
      first reported case of acute suppurative thyroiditis and abscess formation
      occurring within a primary intrathoracic goiter.

PMID- 15251489
TI  - Combined octreotide and insulin therapy in acromegaly.
AB  - OBJECTIVE: To describe an unusual treatment strategy for certain patients with
      both acromegaly and insulin-requiring diabetes. METHODS: We present a case
      history of a man with a pituitary adenoma and diabetes mellitus and chronicle his
      response to various treatment modalities. RESULTS: Acromegaly, a disease state
      with excess growth hormone (GH) and insulin-like growth factor-I, is associated
      with carbohydrate intolerance. Octreotide, a somatostatin analogue, is used in
      the treatment of acromegaly to lower GH levels. Despite effective lowering of GH
      levels, certain patients with acromegaly have persistent or even worsening
      carbohydrate intolerance and may require insulin therapy. Such a regimen would
      necessitate five or more injections per day. We describe a 51-year-old man who
      was diagnosed with a GH-producing pituitary adenoma in 1987. Despite
      transsphenoidal resection, frontal craniotomy, and radiation therapy, symptoms
      and increased levels of GH persisted. The patient was diagnosed with diabetes
      mellitus in August 1989 and treated with glipizide. Because of persistently
      increased GH levels, he was treated with octreotide. His glycohemoglobin level
      increased to 21% despite use of maximal doses of glipizide. The patient refused
      insulin therapy because of his objection to numerous daily injections. Despite
      adjustments in diet and exercise, glycemic control remained poor. As a trial, we
      thus attempted combining octreotide and regular insulin in the same syringe and
      administering the medications in a single subcutaneous injection. No precipitate
      formation was evident, and he had no adverse effects. Glucose control improved,
      and the glycohemoglobin level was lower but still elevated. GH levels remained at
      less than 5 ng/mL. His symptoms of acromegaly were unchanged, but his overall
      attitude and energy level improved. CONCLUSION: The efficacy of the individual
      components of this treatment was demonstrated in the combination of insulin and
      octreotide. The combined administration of insulin and octreotide has limited
      application in patients with acromegaly and insulin-requiring diabetes mellitus.

PMID- 15251490
TI  - Primary hyperparathyroidism: diagnosis and management.
AB  - OBJECTIVE: To review the manifestations of primary hyperparathyroidism and the
      available treatment strategies. METHODS: The epidemiologic and pathologic
      features of this endocrine disorder are outlined. Guidelines for surgical
      intervention are discussed, and the effectiveness of various medical treatments
      is summarized. RESULTS: Primary hyperparathyroidism, a common disorder, is
      diagnosed on the basis of hypercalcemia in the presence of increased parathyroid
      hormone levels as measured by immunoassay. Clinical manifestations are variable
      with many patients being asymptomatic at the time of diagnosis. Patients with
      severe disease require definitive surgical treatment. Surgical cure rates are
      high--approximately 95% in experienced hands. Indications for surgery include a
      serum calcium of more than 2.9 mmol/L (12 mg/dL), osteoporosis, recurrent renal
      stones, and parathyroid carcinoma. As well, it is recommend in individuals
      younger than 50 years of age. Patients with mild disease may have a benign
      natural history and may not have progression to severe disease. Asymptomatic
      individuals with mild hypercalcemia and close to normal bone mass and renal
      function may be managed medically, particularly those who are over the age of 50
      years. Medical management includes ensuring adequate hydration and avoiding
      volume depletion. Estrogen therapy is valuable in postmenopausal women without
      contraindications to hormone replacement. Calcitonin has been shown to decrease
      serum calcium levels on a short-term basis. Bisphosphonates are also potential
      treatment options and require further study. Calcium-mimetic agents also may
      become valuable in the medical management of primary hyperparathyroidism in the
      near future. CONCLUSION: As primary hyperparathyroidism is being increasingly
      detected at an asymptomatic stage, medical therapy is assuming a greater role in
      the effective management of this common condition.

PMID- 15251491
TI  - Hypertension in elderly persons.
AB  - OBJECTIVE: To provide an overview of the prevalence of hypertension in the
      elderly population and discuss the advantages and disadvantages of various
      classes of antihypertensive drugs. METHODS: We review the published clinical
      trials on treatment of elderly patients with hypertension and describe adverse
      reactions that are frequently associated with antihypertensive therapy. RESULTS:
      On the basis of the standard for control of hypertension established by the
      National Health and Nutrition Examination Survey for 1988-1991 (140/90 mm Hg),
      almost 75% of all African-Americans and 50% of all whites 60 to 74 years of age
      have hypertension. If modifications in lifestyle (such as weight reduction and
      increase in exercise) do not normalize blood pressure levels, drug therapy is
      warranted. Meta-analyses of major trials of treatment of hypertension have
      revealed significant reductions in cardiovascular-related mortality and stroke,
      and available data indicate that prudent use of antihypertensive agents is
      associated with an acceptable degree of toxicity. Low-dose thiazide diuretics and
      b-blockers remain the agents of choice. CONCLUSION: Several trials have
      substantiated the effectiveness of treatment of hypertension in elderly subjects.
      Drug therapy should be initiated at low doses, and careful follow-up should
      monitor for adverse effects.

PMID- 15251492
TI  - Selecting antihypertensive drug therapy: the JNC-V controversy.
AB  - OBJECTIVE: To present both the supporting and the opposing arguments for the
      fifth set of recommendations issued by the Joint National Committee on Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC). METHODS: The published
      studies are reviewed, and the various opinions are discussed. RESULTS: The 1993
      recommendation from the JNC that diuretics or beta-adrenergic blockers be
      preferred for therapy in most patients with hypertension has proved
      controversial. This recommendation derived primarily from recent long-term
      studies showing convincing reductions in cardiovascular morbidity and mortality
      when these agents are used to control hypertension. Comparable data have not yet
      been obtained for newer agents, such as calcium channel blockers and angiotensin
      converting enzyme inhibitors. Nonetheless, some critics of the JNC recommendation
      still favor the newer agents because of their putatively superior side-effect
      profile, from both a metabolic and a compliance standpoint. CONCLUSION: The issue
      of optimal antihypertensive drug therapy will not be definitively resolved until
      long-term studies directly comparing the various classes of agents are completed
      in future years.

PMID- 15251493
TI  - Primary hyperaldosteronism.
AB  - OBJECTIVE: To characterize the syndrome of primary aldosteronism and summarize
      diagnostic and therapeutic strategies. METHODS: We review the mechanisms of
      action of aldosterone and outline features that distinguish the major subtypes of
      aldosteronism. RESULTS: The state of aldosterone excess should be suspected in
      every patient manifesting hypertension and hypokalemia. The documentation of low
      renin activity and high plasma aldosterone concentration in such patients
      suggests the presence of primary aldosteronism. Lack of appropriate suppression
      of plasma aldosterone after saline infusion is thought to be the best maneuver
      for confirming primary aldosteronism. Nonetheless, a similar lack of aldosterone
      suppressibility after either oral salt loading for 3 days or oral administration
      of a single 25-mg dose of captopril may help achieve the same purpose. Once
      primary aldosteronism has been diagnosed, the distinction between two major
      subtypes--unilateral adrenal adenoma or Conn's syndrome and bilateral idiopathic
      adrenal hyperplasia--is important because of the difference in management.
      Certain physiologic maneuvers, such as change of posture from supine to upright,
      oral administration of cyproheptadine, and radiologic localization with several
      techniques including iodocholesterol scanning and adrenal venous sampling, will
      almost always help distinguish unilateral adenoma from bilateral hyperplasia.
      CONCLUSION: The distinction between adrenal adenoma and adrenal hyperplasia is
      critical because of the varied approach to treatment. Most patients with
      bilateral adrenal hyperplasia are managed medically with an aldosterone
      antagonist such as spironolactone, whereas most unilateral adenomas are resected
      after correction of hypertension and hypokalemia with appropriate medical
      therapy.

PMID- 15251494
TI  - Intracavernosal injection therapy and other treatment options for erectile
      dysfunction.
AB  - In the United States, almost 30 million men have complete or partial erectile
      dysfunction. This disorder occurs in approximately 52% of men between 40 and 70
      years of age; 70% of affected men younger than 35 years of age have psychogenic
      causes, and 85% of men older than 50 years of age have organic impotence.
      Furthermore, erectile dysfunction is exacerbated by the presence of such
      conditions as heart disease, diabetes, and hyperlipidemia and the medications
      used to manage them. Thus, a widespread segment of the population is in need of a
      safe and effective treatment strategy for restoration of normal sexual function.
      The technique of intracavernosal injection therapy was initially described in the
      early 1980s. During the subsequent decade, the effectiveness of various drug
      combinations and the associated side effects were demonstrated. In 1995,
      prostaglandin E(1) was approved for intra-cavernosal pharmacotherapy. It has
      proved highly effective for neurogenic, vasculogenic, and psychogenic erectile
      dysfunction, with reported response rates of 75 to 92%. The major side effect
      (albeit uncommon) is corporal fibrosis. Other options for treatment of erectile
      dysfunction are vacuum-erection devices and penile prostheses.

PMID- 15251496
TI  - Prospective study of serum androgen levels stratified by increased or normal
      serum follicle-stimulating hormone in infertile women with regular menses.
AB  - OBJECTIVE: To evaluate serum androgen levels in infertile perimenopausal women
      who were still euestrogenic and had regular menses. METHODS: We compared 48 women
      who had early follicular serum follicle-stimulating hormone (FSH) levels of =10
      mIU/mL (group 1) with 50 women who had early follicular serum FSH levels of >15
      mIU/mL (group 2). RESULTS: No differences were detected between groups 1 and 2 in
      early follicular mean levels of dehydroepiandrosterone sulfate (DHEAS) (157
      versus 167 mg/dL). Mean serum testosterone, free testosterone, and
      androstenedione levels, however, were significantly lower in the group with
      higher FSH levels (group 2) than in group 1 (27.6 versus 35.8 ng/dL, 1.3 versus
      2.1 pg/mL, and 130 versus 164 ng/dL, respectively; P<0.05). No differences were
      detected between groups 1 and 2 in the frequency of increased DHEAS,
      testosterone, free testosterone, or androstenedione levels as well as the
      frequency of low serum DHEAS levels. The group with FSH levels of >15 mIU/mL,
      however, had a significantly greater frequency of patients with low levels of
      testosterone, free testosterone, and androstenedione than did the group with
      lower FSH levels: 54% versus 33%; 26% versus 10%; and 26% versus 10%,
      respectively (P<0.05). CONCLUSION: We found no evidence that infertility problems
      in perimenopausal women are complicated by increasing androgen levels. The
      mechanism for lower androgen levels is not apparent.

PMID- 15251497
TI  - Noncardiogenic pulmonary edema complicating diabetic ketoacidosis.
AB  - OBJECTIVE: To alert physicians to the possibility of pulmonary edema as a
      complication of diabetic ketoacidosis. METHODS: We report a case of adult
      respiratory distress syndrome after resuscitative efforts to compensate the first
      episode of diabetic ketoacidosis in a previously healthy young woman. RESULTS: In
      a 26-year-old woman with a 3-day history of malaise, polyuria, nausea, and
      vomiting, severe hypoxia and rales developed, and intubation and mechanical
      ventilation became necessary. Hemodynamic evaluation and striking electron
      microscopic findings on open-lung biopsy confirmed the diagnosis of adult
      respiratory distress syndrome. Despite adequate ventilatory support and
      hemodynamic management, death ensued and was attributed to irresponsive and
      progressive acute respiratory failure due to increased pulmonary capillary
      permeability edema. CONCLUSION: Clinicians should be aware of this possibly fatal
      pulmonary complication of diabetic ketoacidosis.

PMID- 15251498
TI  - Parathyroid reoperation with use of technetium 99m sestamibi radiolocalization
      and an intraoperative gamma counter.
AB  - OBJECTIVE: To describe a new intraoperative technique for localization of
      abnormal parathyroid tissue. METHODS: We report a case and discuss the
      difficulties encountered in reexploration of the neck area. RESULTS: Parathyroid
      reoperation remains a formidable challenge to even the most experienced endocrine
      surgeon. Despite the advances in radiographic imaging and localization
      techniques, accurate intraoperative identification of abnormal parathyroid tissue
      in a scarred field with obliterated anatomic planes is frequently tedious and
      occasionally unsuccessful. In a 48-year-old woman with hyperparathyroidism,
      extensive exploration of the area identified (on the basis of preoperative
      magnetic resonance imaging and technetium 99m sestamibi scans) as suspicious for
      the presence of abnormal parathyroid tissue revealed only an aberrant vein. With
      use of a handheld gamma counter to provide intraoperative guidance during
      parathyroid reexploration after preoperative intravenous injection of technetium
      99m sestamibi, quick identification of a small, intrathyroidal, fifth gland
      adenoma responsible for persistent primary hyperparathyroidism was facilitated.
      CONCLUSION: Because of suboptimal precision and specificity, current preoperative
      localization studies can occasionally provide misleading information.
      Particularly in difficult cases of parathyroid reexploration, an instrument
      capable of localizing abnormal parathyroid tissue, which can be used
      intraoperatively with ease, can be an invaluable tool to ensure a safe,
      expedient, and successful surgical outcome.

PMID- 15251499
TI  - Polyostotic osteonecrosis in a patient with celiac disease.
AB  - OBJECTIVE: To emphasize the role of history and physical examination in the
      clinical evaluation of hypocalcemia and to describe a patient with celiac sprue
      and multiple osteonecrosis, a previously unrecognized association. METHODS: A
      case report is presented of a 39-year-old man with mild hypocalcemia, diarrhea,
      and arthralgias, and the appropriate clinical and laboratory assessment for these
      complaints is outlined. RESULTS: Secondary hyperparathyroidism, celiac sprue, and
      extensive osteonecrosis were detected by hematologic and radiologic studies. The
      hematologic variables normalized after institution of a gluten-free diet and
      calcium supplementation. CONCLUSION: This is the first report of celiac sprue and
      osteonecrosis in one patient. A possible causal relationship due to secondary
      hyperparathyroidism is suggested, and alternative explanations are discussed.

PMID- 15251500
TI  - Practical tips on coding for diabetes care.
AB  - This article is designed to assist with the challenging effort to obtain
      reimbursement for health-care services to patients with diabetes. The basics of
      coding diagnoses and services are presented, including background information and
      specific examples of the use of codes that are particularly pertinent to the
      clinical endocrinologist's care of the patient with diabetes. The coding of
      diagnoses with use of the current International Classification of Diseases, 9th
      revision, clinical modification (ICD-9-CM) classification system and the coding
      of outpatient and inpatient services by using current procedural terminology
      (CPT) codes and modifiers are outlined, including the use of the relatively new
      prolonged physician services codes. A discussion of reimbursement for diabetes
      education and pertinent revenue codes for hospital services is included, and
      resource references for further study are provided.

PMID- 15251501
TI  - Management of congenital adrenal hyperplasia during pregnancy.
AB  - OBJECTIVE: To provide an overview of the congenital adrenal hyperplasias (CAHs)
      and their management during pregnancy. METHODS: Pathways of steroid biosynthesis
      and inherited deficiencies of required enzymes are reviewed, and applications to
      prenatal diagnosis and treatment of affected fetuses are discussed. RESULTS: The
      CAHs are a group of inherited enzymatic defects of adrenal steroid biosynthesis.
      During pregnancy, maternal problems are confined to women with 21-hydroxylase
      deficiency, 11b-hydroxylase deficiency, and 3b-hydroxysteroid dehydrogenase
      deficiency because other adrenal enzyme deficiencies are incompatible with
      fertility. The interposition of the placenta on the hypothalamic-pituitary
      adrenal axis has a major effect on clinical evaluation of CAH during pregnancy.
      Women with severe forms of CAH have decreased fertility rates because of oligo
      ovulation, and successful conception requires a combination of good therapeutic
      compliance, careful endocrine monitoring, and often induction of ovulation. 21
      Hydroxylase deficiency in the fetus can now be diagnosed accurately prenatally by
      endocrine testing and molecular genetic techniques. Prenatal diagnosis of 11b
      hydroxylase deficiency in the fetus by endocrine testing is not as sensitive.
      Prevention of masculinization of affected female fetuses by corticosteroid
      suppression has been attempted in both 21-hydroxylase deficiency and 11b
      hydroxylase deficiency CAH, with variable degrees of success. To date, no reports
      have been published of prenatal diagnosis or treatment of affected female fetuses
      with 3b-hydroxysteroid dehydrogenase deficiency CAH. CONCLUSION: Endocrine and
      genetic studies of CAH during pregnancy have improved the diagnosis and
      management.

PMID- 15251502
TI  - The spectrum of postpartum thyroid dysfunction: diagnosis, management, and long
      term prognosis.
AB  - OBJECTIVE: To provide an overview of thyroid abnormalities that can occur after
      delivery. METHODS: We review the diagnosis and management of various types of
      postpartum thyroid dysfunction. RESULTS: A common problem during the postpartum
      period, thyroid dysfunction is found in approximately 5% of new mothers in the
      general population. Such thyroid dysfunction can manifest in various forms
      (hyperthyroid or hypothyroid, transient or persistent), each of which
      necessitates different treatment. The most common type of thyroid dysfunction is
      destructive thyrotoxicosis, which is due to the aggravation of autoimmune
      thyroiditis. It occurs at 1 to 3 months after delivery as sudden thyrotoxicosis
      and lasts for 1 to 3 months, after which transient hypothyroidism may ensue in
      some cases. Simply symptomatic treatment may be sufficient for such transient
      thyroid dysfunctions. Postpartum Graves' disease is found in approximately 11% of
      the cases of postpartum thyroid dysfunction. Graves' hyperthyroidism usually
      occurs at 3 to 6 months after parturition. In the treatment of postpartum Graves'
      disease, one may choose radioactive iodine, antithyroid drugs, or surgical
      therapy; however, transient Graves' hyperthyroidism, which often occurs in
      patients with postpartum Graves' disease, may require neither radioactive iodine
      therapy nor thyroidectomy. Mothers at high risk for development of postpartum
      thyroid dysfunction can be screened by testing for antimicrosomal antibodies.
      Although a strong correlation exists between the presence of antimicrosomal
      antibodies and postpartum thyroid dysfunction, the cost-effectiveness of
      screening for postpartum autoimmune thyroid syndrome remains controversial.
      CONCLUSION: For optimal management of the postpartum conditions of Graves'
      disease, destructive thyrotoxicosis, and hypothyroidism, the clinician should be
      aware of diagnostic techniques that will facilitate early intervention or will
      prompt careful surveillance.

PMID- 15251504
TI  - Perspective from a hotbed of managed care.
AB  - An environmental assessment of the current healthcare market in the United States
      shows four stages of evolution: (1) the unstructured stage, (2) the loose
      framework, (3) consolidation, and (4) managed competition. Recognition of these
      stages should help in the development of strategies for the future. After
      determining the existing stage of the health-care market in a particular
      geographic area, clinical endocrinologists can compose a vision statement,
      develop goals and objectives, and formulate strategies to achieve the established
      goals. For example, one strategy is to join a managed-care plan. Some practical
      business advice about assuming risk (responsibility) for various health-care
      services is provided, and the concept of disease-specific capitation is
      discussed. Health-care reform is likely to proceed regardless of what the federal
      government does. In the managed-care environment, the most successful physician
      participants will be those who are thoroughly informed.

PMID- 15251505
TI  - Lessons from managed care.
AB  - The infiltration of the health-care environment by health maintenance
      organizations has been promoted, in part, by instilling fear in physicians about
      their patient base and creating an illusion of free choice for patients. Within
      capitation arrangements, specialists are often underpaid for management of
      complex cases and uncompensated for investment of long hours in ancillary
      activities. Clinical endocrinologists have been expected to develop algorithms
      for conditions such as diabetic ketoacidosis, yet application of such guidelines
      by other clinicians may yield suboptimal results. The transformation of medicine
      to a business and the focus of insurance administrators on profit rather than
      high-quality care currently tend to eliminate specialists. Studies that show that
      high-quality specialty care improves outcomes clinically (and therefore
      financially) should curb this trend. Nevertheless, a new paradigm for medical
      care is evolving. Because capitation will not be the only model, clinical
      endocrinologists should not allow themselves to be exploited in such an
      arrangement.

PMID- 15251506
TI  - Stages of managed-care evolution.
AB  - In the United States, health care is undergoing a transformation. The stages of
      evolution to a managed-care setting could be characterized as follows: (1) "The
      Push," (2) "The Squeeze," (3) "The Purge," and (4) "The Promise." Although the
      pace of change differs in various locations, these same stages will be
      experienced throughout the country. In the first stage, the move is toward per
      diems for hospitals, and payers are still focused on volume. In stage 2,
      integrated systems are beginning to develop, and payers are purchasing volume by
      negotiating deals. Primary physicians begin to flex their muscles, and
      specialists begin to panic. In stage 3, price clout rules, and results of quality
      measures will be reported. In the final stage, fewer health-care providers will
      be available, but they will be coordinated in large groups, and capitation
      contracts will prevail. Capitation--a fixed payment per health plan enrollee
      being paid to a provider for a defined set of services for a prescribed period-
      will replace a fee-for-service arrangement. In this managed-care setting, the
      management of diabetes, which afflicts 14 million Americans, is a major issue. It
      accounts for 14.7% of every health-care dollar spent in the United States, and
      much of that investment is for treatment of unnecessary complications.
      Positioning of the clinical endocrinologist as the primary-care physician for
      patients with diabetes is proposed as the optimal strategy for appropriate
      management of the patient and attainment of cost control.

PMID- 15251507
TI  - Capitation in managed care.
AB  - The current trend in the health-care setting is a change from indemnification to
      capitation for services and to negotiation of reduced payments to health-care
      providers. Although attempts to socialize medicine in the United States have
      failed, the medical establishment will be forced to be scaled back because of the
      oversupply of physicians, an excessive number of hospital beds, and exorbitant
      costs for services. In addition, the insurance industry will experience attrition
      as developments in technology enhance the ability to quantify and forecast the
      health status of individuals and populations. The risk will then shift from the
      insurance companies to the providers of care (physicians and hospitals--those who
      were perceived to have benefited in the past by accruing capital and are now
      considered able to bear the risk). A key factor in the future of medicine is the
      accumulation and manipulation of data. Those who control the data first will have
      an advantage in controlling market penetration and market share.

PMID- 15251508
TI  - Capitation and control of risk in managed care.
AB  - In the environment of capitation for health care, physicians assume risks for the
      condition of their patients and, in essence, act as a type of insurance company.
      For example, in patients with diabetes, risks include retinopathy and cataracts,
      peripheral vascular disease and amputations, cardiovascular disease,
      hyperlipidemia, hypertension, high-risk pregnancies, and renal failure as well as
      its long-term consequences. Transplantation and million-dollar births are
      uncommon but extremely expensive events that may be best managed by a partnering
      arrangement that distributes the risk (and also shares in the potential profit).
      Health maintenance organizations manage risks by eliminating high-cost patients,
      decreasing length of stay, and reducing payments to physicians. In formulation of
      a proposal to assume care for a specific population, the characteristics of the
      patients and their history of utilization of health-care services should be well
      understood. With background information, projection of risks becomes more
      accurate. For management of a contract under capitation, the ability to track
      long-term outcomes will help to optimize the health care provided.

PMID- 15251509
TI  - Sertoli-Leydig cell tumor of the ovary: a case report with endocrinologic
      observations.
AB  - OBJECTIVE: To present a case of a Sertoli-Leydig cell ovarian tumor and discuss
      the endocrinologic findings. METHODS: We describe the clinical manifestations in
      a female patient with an ovarian tumor and summarize the results of hormonal
      studies. RESULTS: A 33-year-old woman with abrupt cessation of menses,
      progressive hirsutism, and weight gain because of a unilateral ovarian mass
      identified sonographically and an increased serum testosterone level underwent
      laparotomy, which disclosed a left ovarian Sertoli-Leydig cell tumor.
      Hysterectomy and bilateral adnexectomy were performed. Tissue extraction studies
      revealed 17-hydroxyprogesterone as the predominant steroid in tumor tissue in
      conjunction with substantially increased testosterone, free testosterone,
      dihydrotestosterone, androstenedione, and dehydroepiandrosterone levels and left
      ovarian vein effluent. CONCLUSION: A unilateral ovarian mass associated with
      substantially increased serum testosterone should suggest the presence of a
      functioning ovarian tumor. Androgenic symptoms are a consequence of disturbed
      steroidogenesis from multipotential steroidogenic cells of ovarian stromal origin
      whose clinical effects depend on enzymatic specificity and the relative
      concentrations of steroids produced.

PMID- 15251510
TI  - Diabetes management during glucocorticoid therapy for nonendocrine disease.
AB  - OBJECTIVE: To determine current attitudes about management of diabetes during
      glucocorticoid therapy for nonendocrine disease, as assessed by a pilot survey.
      METHODS: A 27-item questionnaire was designed to determine areas of consensus and
      of disagreement on diabetes management during glucocorticoid therapy for
      nonendocrine disease and was mailed to 84 Chicago-area academic general
      internists, endocrinologists, pulmonologists or allergists, rheumatologists, and
      certified diabetes nurse-educators. RESULTS: The response rate was 55%. For new
      onset "steroid diabetes," 43% of respondents agreed with use of insulin and 44%
      with use of sulfonylurea therapy. Respondents indicated 91 to 95% agreement on
      the desirability of self-monitoring of blood glucose on initiation of
      glucocorticoid therapy. For a fasting plasma venous glucose level of 150 mg/dL at
      the time of initiation of long-term glucocorticoid therapy, 54% of respondents
      disagreed with immediate increase of insulin in the case of a patient already
      taking insulin, and 80% disagreed with immediate substitution of insulin in the
      case of a patient on maximal glyburide therapy (P = 0.0053 for mean change of
      position). During tapering of glucocorticoid therapy, 75% of respondents approved
      close observation without immediate insulin reduction. Two anticipatory
      management plans, opposed by 54% and 45% of respondents, respectively, elicited
      strongly correlated attitudes: immediate increase of NPH insulin dosage during
      initiation of glucocorticoid therapy and immediate reduction of NPH insulin dose
      during tapering of glucocorticoids (r = 0.6296; P<0.0001). Finally, 78% perceived
      a paucity of objective information about diabetes management during
      glucocorticoid therapy for nonendocrine disease. CONCLUSION: The surveyed sample
      of practitioners reported a paucity of objective data about management of
      diabetes during glucocorticoid therapy for nonendocrine disease and conservatism
      in adjusting diabetes management during initiation and tapering of glucocorticoid
      therapy.

PMID- 15251511
TI  - Hypokalemia in a patient with pheochromocytoma.
AB  - OBJECTIVE: To report the occurrence of hypokalemia in a patient with
      pheochromocytoma. METHODS: We present a case report and discuss the possible role
      of hyperepinephrinemia as a cause of hypokalemia. RESULTS: A patient with
      pheochromocytoma had hypokalemia associated with vomiting, but hypokalemia
      recurred after repletion of potassium and cessation of vomiting. She had
      substantially increased epinephrine concentrations in the plasma and in the
      subsequently excised pheochromocytoma. Because evidence has shown that infusions
      of epinephrine induce hypokalemia in normal human subjects, the relationship
      between serum potassium and plasma epinephrine concentrations in 16 previous
      patients with pheochromocytoma and 4 patients with primary hyperepinephrinemia
      was studied. A significant negative correlation was noted. CONCLUSION: The
      presence of hypokalemia and its potential role in predisposing to arrhythmias in
      patients with pheochromocytoma merit further study.

PMID- 15251512
TI  - Fasting blood glucose levels and initiation of insulin therapy in gestational
      diabetes.
AB  - OBJECTIVE: To determine whether an initial fasting blood glucose determination
      will predict which pregnant women will need insulin in addition to dietary
      measures to maintain fasting glucose levels during gestation. METHODS: All women
      referred for management of gestational diabetes received dietary counseling and
      instructions for self-monitoring of blood glucose levels during fasting and at 2
      hours after each meal. Insulin therapy was initiated if the fasting blood glucose
      value exceeded 5.8 mmol/L (105 mg/dL) on more than one occasion, the 2-hour
      postprandial glucose exceeded 8.3 mmol/L (150 mg/dL), or the 2-hour postprandial
      glucose exceeded 6.7 mmol/L (120 mg/dL) three times in a week. The use of diet
      alone or diet plus insulin therapy was determined by review of medical records.
      RESULTS: Fifty-two pregnant women with fasting blood glucose levels of less than
      5.8 mmol/L (105 mg/dL) and with two or more elevated blood glucose values on a 3
      hour glucose tolerance test underwent follow-up at least through the 36th week of
      gestation. In 21 patients, insulin therapy was initiated in addition to diet. Two
      of five women with an initial fasting glucose level of less than 4.4 mmol/L (80
      mg/dL) required insulin, and 8 of 24 women with fasting levels of 5.3 to 5.8
      mmol/L (96 to 105 mg/dL) eventually needed insulin. CONCLUSION: The height of the
      fasting blood glucose level in women with gestational diabetes does not separate
      those who will maintain blood glucose levels in the targeted therapeutic range on
      diet alone from those who will need insulin. Therefore, all women with
      gestational diabetes need to participate in self-monitoring of blood glucose
      levels.

PMID- 15251513
TI  - Medical therapy for prolactinomas and somatotroph adenomas.
AB  - OBJECTIVE: To review the current recommendations for medical treatment of
      prolactinomas and somatotroph adenomas. METHODS: The spectrum of symptoms of
      hyperprolactinemia and the clinical features of acromegaly are elaborated, and
      the various medical therapeutic options for management of prolactinomas and
      somatotroph adenomas are discussed. RESULTS: In patients with prolactinomas,
      medical therapy with a dopamine agonist constitutes the primary treatment and is
      usually associated with normalization of prolactin levels, tumor shrinkage, and
      resolution of clinical symptoms. For patients intolerant of bromocriptine,
      currently the only available dopamine agonist approved for prolactinomas in the
      United States, several other options can be explored. Somatotroph adenomas are
      treated first by using a transsphenoidal neurosurgical approach. For those
      patients not cured, medical therapy with octreotide, a somatostatin analogue, can
      be effective in biochemical and symptomatic control of the residual acromegaly.
      This medical option can be used in conjunction with radiation therapy while
      awaiting its effects or as the sole secondary therapy for this disorder.
      CONCLUSION: Medical therapy has an important role in the management of
      prolactinomas and somatotroph adenomas.

PMID- 15251514
TI  - Menopause: a major challenge for endocrinologists.

PMID- 15251516
TI  - The American College of Physicians versus the National Cholesterol Education
      Program: should endocrinologists listen?

PMID- 15251515
TI  - Is endocrinology of the reproductive system a part of clinical endocrinology?

PMID- 15251517
TI  - Diagnosis and management of diabetes insipidus during pregnancy.
AB  - OBJECTIVE: To provide an overview of diagnostic and treatment strategies in
      pregnant patients with diabetes insipidus (DI). METHODS: We review the changes in
      osmoregulation during normal pregnancy, characterize the various types of DI that
      can occur during pregnancy, and discuss the recommended management. RESULTS: The
      incidence of DI is 2 to 4 cases per 100,000 gestations. Central DI can precede
      pregnancy or manifest initially during gestation. With preexistent central DI,
      pregnancy usually aggravates the disorder, and the requirements for antidiuretic
      hormone (ADH) usually increase. Such an effect is less likely to be noted in ADH
      independent nephrogenic forms of DI. Currently, the major type of DI associated
      with pregnancy is a transient syndrome that is resistant to arginine vasopressin
      (AVP) but responsive to desmopressin (dDAVP); such cases of DI are often
      associated with liver abnormalities or preeclampsia. This syndrome is explained
      by excess vasopressinase, a placental enzyme which degrades AVP but not dDAVP. A
      transient recurrent type of DI can occur during gestation in patients with
      limited ADH-secreting capacity and is responsive to both AVP and dDAVP. Latent
      central DI manifesting after complicated delivery and transient nephrogenic DI,
      resistant to both AVP and dDAVP, have also been reported. CONCLUSION: The
      differential diagnosis of polyuric and polydipsic states during pregnancy is
      broad, and precise diagnosis may be difficult. The use of dDAVP to treat DI
      during gestation has proved effective and safe for both the mother and the fetus.

PMID- 15251518
TI  - Primary hyperparathyroidism during pregnancy.
AB  - OBJECTIVE: To provide an up-to-date review of primary hyperparathyroidism (HPT)
      as a complication of pregnancy. METHODS: We discuss the initial manifestations of
      primary HPT in pregnant patients, the diagnosis, the differential diagnosis of
      hypercalcemia, and the recommended treatment strategies. RESULTS: In the
      nonpregnant state, 50 to 80% of patients with primary HPT are asymptomatic. In
      contrast, pregnant patients with primary HPT have a wide variety of symptoms and
      findings: gastrointestinal symptoms (nausea, vomiting, and anorexia), weakness
      and fatigue, headaches and confusion, nephrolithiasis, bone disease,
      pancreatitis, urinary tract infection, and hypertension. Occasionally, neonatal
      hypocalcemia is the initial manifestation of maternal HPT. Diagnosis of primary
      HPT during pregnancy is dependent on the clinical history and laboratory
      findings. In general, management of maternal primary HPT during pregnancy should
      be individualized and based on the patient's symptoms, general medical condition,
      severity of disease, and gestational stage at the time of diagnosis. If HPT is
      diagnosed during the first two trimesters, surgical intervention is the treatment
      of choice. CONCLUSION: Although uncommon, HPT during pregnancy may be associated
      with maternal and perinatal complications. Therefore, clinicians should be aware
      of the usual characteristics of this disorder and the preferred management
      options.

PMID- 15251520
TI  - Results of a community thyroid screening program: who will benefit?
AB  - OBJECTIVE: To describe the results of a community-based thyroid screening
      program. METHODS: We review the recruitment process, the screening questionnaire,
      the laboratory procedure, and the data analysis. RESULTS: News media
      advertisements and facility-sponsored communications were used to recruit 1,176
      participants, each of whom completed a health questionnaire and had blood
      withdrawn for a thyroid-stimulating hormone (TSH) assay. Most participants were
      female (78%), Caucasian (92%), and age 50 years or older (61%). Data from 1,139
      participants were analyzed. Abnormal TSH values were found in 107 participants:
      TSH was low in 21 (2%) and elevated in 86 (8%). Elevated TSH values occurred in
      8% of females, 7% of males, 8% of Caucasians, and 7% of Hispanics. Although the
      percentage of elevated TSH values tended to increase with advancing age,
      primarily in females, 5% of participants younger than 50 years of age had an
      elevated TSH. No associations were apparent between abnormal TSH values and
      health maintenance organization membership, self-rating of overall health, or
      presence of thyroid-related symptoms. Participants who rated their overall health
      as "excellent" or "very good" accounted for 48% of the TSH values >12 microIU/mL.
      CONCLUSION: Experience gained from the conduct of this screening program may help
      shape the expectations of future screening programs that use disease awareness
      and self-motivation and provide insights into program design that may maximize
      participation by the desired target audiences.

PMID- 15251521
TI  - Recurrent acute primary hyperparathyroidism in an adult male patient.
AB  - OBJECTIVE: To report the occurrence of recurrent acute primary
      hyperparathyroidism (HPT), a rare disorder that occurs in only 1 to 2% of
      patients with primary HPT. METHODS: We describe a patient who had two separate
      episodes of acute primary HPT and discuss the appropriate treatment of
      parathyroid crisis. RESULTS: In 1990, primary HPT developed in a 41-year-old man,
      who underwent surgical removal of a parathyroid adenoma. He remained
      normocalcemic until 1995, when acute primary HPT developed after lithium therapy
      was initiated because of depression. Calcium and parathyroid hormone (PTH) levels
      declined after lithium therapy was discontinued, but they remained slightly above
      the normal range. Nine months later, he was rehospitalized with acute primary
      HPT. After stabilization, a second parathyroid adenoma was successfully resected,
      and calcium and PTH levels subsequently remained normal. In this disorder, levels
      of PTH are increased up to 20 times normal, and the clinical manifestations are
      similar to parathyroid carcinoma. Treatment involves rehydration, antiresorptive
      agents, and parathyroidectomy. Our patient initially was thought to have lithium
      induced primary HPT, which can occur in up to 10% of patients on long-term
      lithium therapy. The mechanism is unknown but may be an alteration of the calcium
      PTH "set-point." CONCLUSION: Patients with asymptomatic primary HPT should have
      close follow-up because of the risk of development of acute primary HPT. Patients
      at risk, such as those with immobilization or severe illness, should be
      identified. Drugs known to interfere with calcium metabolism (for example,
      lithium) should be avoided in patients with primary HPT.

PMID- 15251522
TI  - Large lymphangioma of the adrenal gland: case report.
AB  - OBJECTIVE: To characterize adrenal lymphangiomas and discuss management
      strategies based on findings. METHODS: We present a case report and review the
      pertinent literature. RESULTS: In a 35-year-old man with painless hematuria for
      several days, a computed tomographic (CT) scan of the abdomen disclosed an 8-cm
      right adrenal mass. It had the appearance of a loculated cyst with several
      septations. The histologic diagnosis of the excised lesion was lymphangioma with
      cystic degeneration. The most frequently occurring cystic adrenal masses are
      endothelial lesions. Lymphangiomas of the adrenal gland have a characteristic
      mutiloculated appearance on ultrasonography and CT. Small asymptomatic smooth
      adrenal cysts with clear fluid can simply be observed, whereas large symptomatic
      adrenal lymphangiomas should be excised. CONCLUSION: The preferred studies for
      detection of adrenal lymphangiomas are CT and ultrasonography. The size of the
      lesion, type of cystic fluid, symptomatic status, and cytologic findings dictate
      management options.

PMID- 15251523
TI  - Coexisting hyperthyroidism and primary hyperparathyroidism with vitamin D
      deficient osteomalacia in a Vietnamese immigrant.
AB  - OBJECTIVE: To present the first report of concurrent hyperthyroidism, primary
      hyperparathyroidism (PHP), and vitamin D-deficient osteomalacia. METHODS: We
      describe the complicated clinical course in a 65-year-old Vietnamese immigrant,
      and underlying factors potentially contributing to her condition are discussed.
      RESULTS: Our patient, who had hyperthyroidism and hypercalcemia, was found to
      have an inappropriately high level of intact parathyroid hormone (PTH) because of
      a parathyroid adenoma, detected on a parathyroid scan. With propranolol
      treatment, however, improvement was noted in both laboratory data--intact PTH,
      ionized calcium, serum total calcium, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and
      urinary cyclic adenosine monophosphate--and findings on ultrasonography and
      nuclear parathyroid scanning. Later, the adenoma was removed surgically. The
      improvement of PHP after administration of a beta-adrenergic blocker suggested
      that the parathyroid adenoma in this patient was not completely autonomous. The
      patient also had vitamin D-deficient osteomalacia that was confirmed by a low
      serum level of 25-hydroxyvitamin D3 (25OHD3) and by bone histomorphometry. This
      coexisting condition was caused by the long-term increase in conversion of 25OHD3
      to 1,25(OH)2D3 from hyperparathyroidism in a patient with low stores of vitamin D
      (which were ascribed to aging, liver dysfunction in hyperthyroidism, a vegetarian
      diet, deprivation of sunlight, and avoidance of dairy products). CONCLUSION: The
      complex concurrence of hyperthyroidism, PHP, and vitamin D-deficient osteomalacia
      is rare but possible.

PMID- 15251524
TI  - Interpretive reporting of laboratory data: proposed criteria to qualify as a high
      quality, limited clinical pathology consultation.
AB  - OBJECTIVE: To present recommended criteria designed to improve the computer-based
      interpretation of laboratory test results. METHODS: Guidelines for providing high
      quality test interpretations and an outline for incorporating such criteria into
      a program for interpretive reporting are presented. RESULTS: Traditionally, when
      a laboratory reports a test result, the clinician interprets it within the
      clinical context. More recently, even in the absence of clinical information
      about the patient, laboratories that report test results, including biochemical
      thyroid function tests, have begun to insert "informative" statements about the
      test. These statements fail to provide an adequate limited pathology consultation
      that merits the CPT code 80500. Such interpretations can be improved by making
      them optional, specific for the test result, considerations rather than
      recommendations, and accompanied, on request, by an expanded list of differential
      diagnoses and an itemization of drugs known to affect the test result.
      CONCLUSION: High-quality interpretations of laboratory tests should improve
      patient care, avoid unnecessary costs, and prompt appropriate referrals to
      specialists.

PMID- 15251525
TI  - Responsibility for interpreting laboratory studies.

PMID- 15251527
TI  - The place of the clinical endocrinologist in health care reform.

PMID- 15251526
TI  - Vitamin D deficiency testing: reimbursement dilemma.

PMID- 15251528
TI  - Clinical utility of C-peptide measurement in diabetes mellitus.

PMID- 15251529
TI  - New orally administered antihyperglycemic agents for the management of patients
      with type ii diabetes and the syndrome of insulin resistance.
AB  - OBJECTIVE: To describe several newly developed orally administered antidiabetic
      drugs, which are effective for type II diabetes. METHODS: Detailed clinical
      information about three types of antihyperglycemic agents--carbohydrase
      inhibitors, biguanides, and thiazolidinediones--is presented. RESULTS: Miglitol
      and acarbose, two a-glucosidase inhibitors, effectively reduce postprandial blood
      glucose values and do not cause hypoglycemia. The biguanide metformin has been
      shown to suppress hepatic glucose production, augment glucose uptake, and enhance
      insulin action in peripheral tissues. Metformin is effective alone or in
      combination with other orally administered antidiabetic agents or insulin. A new
      class of antidiabetic agents called the thiazolidinediones (not yet available for
      clinical use) apparently works by mainly reducing insulin resistance in skeletal
      muscle. The most extensively studied drug in this category is troglitazone.
      Carbohydrase inhibitors as well as biguanides may be useful in patients with the
      insulin resistance syndrome, especially those with obesity, hypertension, and
      hyperinsulinemia. CONCLUSION: Because of the development of new antihyperglycemic
      agents for oral administration, the need for insulin injections in patients with
      type II diabetes will be minimized, and the clinical management of such patients
      will be improved.

PMID- 15251530
TI  - Management of patients with diabetes and "abnormal" blood pressure: selection of
      antihypertensive agents.
AB  - OBJECTIVE: To characterize the association of diabetes and hypertension and to
      discuss management strategies. METHODS: Published studies are summarized and
      various hypotheses are reviewed. RESULTS: Hypertension is a major determinant of
      the increased cardiovascular, peripheral vascular, and renal complications
      associated with diabetes. Recent evidence indicates that insulin resistance is
      one of the multiple key components of the pathophysiologic elements underlying
      the increased prevalence of hypertension associated with diabetes. In patients
      with diabetes, management of hypertension is frequently complicated by the
      coexistence of other macrovascular risk factors, including dyslipidemia, obesity,
      visceral adiposity, and poor glycemic control. The choice of antihypertensive
      agents in both type I and type II diabetes must be based on the selective
      metabolic, hormonal, and hemodynamic advantages and disadvantages of these agents
      in individual patients. CONCLUSION: Long-term trials are needed to determine the
      benefits, if any, of various angiotensin-converting enzyme inhibitors, calcium
      channel antagonists, and alpha1-adrenergic receptor antagonists in preventing the
      cardiovascular and the renal complications of diabetes.

PMID- 15251531
TI  - Management of thyroxine therapy during pregnancy.
AB  - OBJECTIVE: To review the management of thyroxine (T4) therapy in pregnant
      patients with hypothyroidism. METHODS: The results of pertinent published studies
      are summarized, and practical recommendations are presented. RESULTS: The
      conditions for which T4 therapy is administered during pregnancy are the same as
      those in nonpregnant patients: hypothyroidism, thyrotropin or thyroid-stimulating
      hormone (TSH) control after surgical treatment of thyroid cancer, and, in
      selected patients, suppression treatment for postsurgical thyroid remnants,
      thyroid nodules, or goiter. Untreated hypothyroidism during pregnancy can
      potentially cause adverse effects in both mother and fetus. Up to 75% of T4
      treated women with hypothyroidism require higher doses of T4 during pregnancy
      than before or after conception, to maintain serum TSH levels in the normal
      range. Otherwise, in a substantial percentage of these women, subnormal serum
      free T4 levels, TSH elevations >20 microIU/L, or both will develop. The mean T4
      dose needed to correct hypothyroidism during pregnancy is about 150 microg/day,
      but individual dose requirements vary widely. CONCLUSION: The increment in T4
      dose needed to normalize an increased TSH level in women taking T4 can be
      estimated from the serum TSH concentration during pregnancy. Increased TSH levels
      can appear as early as 4 to 8 weeks of gestation or as late as the third
      trimester. Although the optimal schedule is uncertain, assessing the TSH once
      each trimester seems reasonable. After pregnancy, the T4 dose should be reduced
      to the preconception level, and postpartum reassessment should be done at 6 to 12
      weeks.

PMID- 15251532
TI  - Evaluation and management of pituitary tumors during pregnancy.
AB  - OBJECTIVE: To review the recommended management of pituitary tumors that occur in
      pregnant patients. METHODS: Studies from the literature and personal experience
      are summarized, and guidelines for optimal maternal and fetal outcome are
      suggested. RESULTS: Tumors are the most common pituitary disorder affecting
      pregnant patients. Hyperprolactinemia must be corrected to allow ovulation and
      fertility. Bromocriptine has been shown to be safe for use during early
      gestation. Patients have less than a 2% risk of microprolactinoma enlargement
      during pregnancy but approximately a 16% risk of symptomatic enlargement of a
      macroprolactinoma. Treatment options for patients with macroadenomas include
      discontinuing bromocriptine therapy when pregnancy is confirmed and reinstituting
      this treatment if the tumor enlarges; continuous bromocriptine therapy throughout
      the pregnancy; and prepregnancy surgical debulking of the tumor. The diagnoses of
      acromegaly and Cushing's disease are difficult to make during pregnancy. The
      hormone oversecretion in these conditions may exacerbate tendencies to
      gestational diabetes, fluid retention, and hypertension. Cushing's syndrome
      should be treated during pregnancy, but treatment for acromegaly and other tumors
      may be deferred. Rare reports have described enlargement of clinically
      nonfunctioning and growth hormone-secreting tumors during pregnancy, and
      surveillance is needed. Tumors may need to be distinguished from lymphocytic
      hypophysitis. CONCLUSION: Physicians should be aware of the normal pituitary
      changes during pregnancy and the major clinical and laboratory findings
      associated with pituitary tumors for optimal management of pregnant patients.

PMID- 15251533
TI  - Stone bone syndrome--diffuse sclerosis of bone: a newly described clinical
      disorder.
AB  - A 52-year-old man with severe bone pain was found to have diffuse sclerosis of
      bone and chronic hepatitis C infection. A bone biopsy specimen showed a normal
      lamellar appearance but dramatically increased bone-forming surfaces. A possible
      mechanism for this disorder is offered.

PMID- 15251534
TI  - Midcycle steroidal levels after ultra-low-dose pure follicle-stimulating hormone
      stimulation versus human menopausal gonadotropin stimulation in euestrogenic
      women with follicular maturation defects.
AB  - OBJECTIVE: To compare the midcycle endocrine steroidal variables in 32 infertile
      women with follicular maturation defects treated with ultra-low-dose pure
      follicle-stimulating hormone (FSH) or human menopausal gonadotropins (hMG).
      METHODS: A crossover design was used in which women were randomly assigned to a
      treatment modality (pure FSH or hMG) in the first cycle, and the alternative
      treatment was used in the second cycle. In the ultra-low-dose regimen, the dosage
      began at 1 ampule/day (75 IU) and could increase to a maximum of 1.5 ampules/day.
      The mean midcycle serum levels determined at the time of peak follicular
      maturation and before the administration of human chorionic gonadotropin or
      gonadotropin-releasing hormone for release of oocytes were compared. RESULTS: In
      the pure FSH cycle, the mean estradiol (E2), progesterone, and luteinizing
      hormone (LH) levels were 316 +/- 119 pg/mL, 0.6 +/- 0.4 ng/mL, and 23 +/- 22
      IU/L, respectively; in the hMG cycle, the mean E2, progesterone, and LH levels
      were 361 +/- 193 pg/mL, 0.5 +/- 0.4 ng/mL, and 21 +/- 18 IU/L, respectively.
      CONCLUSION: Ultra-low-dose gonadotropin therapy produces similar midcycle
      steroidal levels (E2, progesterone, and LH) whether or not LH is present in
      addition to FSH in the medications used for follicle stimulation.

PMID- 15251535
TI  - Recurrence of Cushing's disease 10 years after transsphenoidal adenomectomy:
      report of a case.
AB  - OBJECTIVE: To report a case of recurrent Cushing's disease after an apparent cure
      and long-term surveillance. METHODS: We describe in detail the follow-up course
      of a woman who underwent transsphenoidal resection of a corticotropin-secreting
      pituitary microadenoma in 1981. RESULTS: For 2 years postoperatively, the patient
      exhibited adrenocortical insufficiency. In 1983, the pituitary-adrenal axis was
      normal. She remained eucorticoid until May 1992, when features of Cushing's
      syndrome redeveloped. Plasma and urine cortisol and plasma corticotropin levels
      were once again increased in conjunction with a loss of diurnal variation and
      abnormal responses to dexamethasone suppression. A magnetic resonance imaging
      scan of the pituitary gland was consistent with a small lesion on the left side,
      and petrosal sinus sampling after ovine corticotropin-releasing hormone
      stimulation was consistent with increased activity on the right side. CONCLUSION:
      This 10-year interval between apparent cure and recurrence appears to be the
      longest thus far reported for a patient with Cushing's disease. These
      observations reinforce the impression that permanent cure of this disorder is
      uncertain and indicate the need for indefinite follow-up.

PMID- 15251536
TI  - Muscle infarction in diabetes: clinical manifestations and course.
AB  - OBJECTIVE: To characterize the initial manifestations and course of muscle
      infarction in diabetes, a rarely diagnosed condition. METHODS: We describe two
      patients with this disorder and review the clinical characteristics of previously
      reported cases. RESULTS: Usually, the initial complaint in patients with muscle
      infarction in diabetes is swelling of the thigh or calf that has evolved over
      days to months. Biopsy of the muscle is often necessary for diagnosis and reveals
      extensive muscle necrosis. Although the pathogenesis is unknown,
      hypercoagulability may have a role. Bilateral involvement and recurrent disease
      are common. Treatment is supportive; our patients required narcotics for
      alleviation of pain. CONCLUSION: Muscle infarction in diabetes may mimic
      thrombophlebitis, soft tissue infection, or a neoplasm. Medical evaluation may be
      directed toward these entities, and the diagnosis of a diabetes-associated
      disorder may be completely overlooked. The presence of atraumatic swelling of an
      extremity in a patient with diabetes should suggest diabetes-related muscle
      infarction.

PMID- 15251537
TI  - Stimulated C-peptide and glucose levels as metabolic criteria to use insulin
      treatment in adult-onset type II diabetes.
AB  - OBJECTIVE: To evaluate plasma C-peptide levels in middle-aged and elderly
      patients with type II diabetes, to clarify their practical use in assessing the
      need for insulin therapy, and to determine their sensitivity in distinguishing
      insulin-requiring from non-insulin-requiring diabetes after improved baseline
      glycemic control. METHODS: Plasma glucose and C-peptide levels were measured in a
      fasting state and 2 hours after an oral challenge with 100 g of glucose in groups
      of obese and normal-weight, glycemic-controlled, middle-aged and elderly patients
      with diabetes treated with insulin or an orally administered hypoglycemic agent
      (OHA). Basal and glucose-stimulated C-peptide levels as well as increased
      stimulated glucose values were contrasted in insulin- versus OHA-treated groups.
      In a second protocol, basal and glucose-stimulated C-peptide reactivity and
      stimulated glucose levels were also measured in eight patients with diabetes,
      before and after glycemic control. RESULTS: Irrespective of the age difference,
      stimulated C-peptide levels in the insulin-treated patients were significantly
      lower than those in the weight-matched OHA patients. Similarly, for both the
      middle-aged and elderly patients, stimulated glucose levels and degree of glucose
      elevation were higher in the insulin-treated patients. In the second protocol, as
      hyperglycemia was reduced, beta-cell secretion measured by C-peptide responses to
      glucose was significantly increased, in conjunction with a decrease in the
      stimulated glucose levels. CONCLUSION: These results indicate that measurements
      of C-peptide responses to glucose stimulation are helpful to determine the
      decision to use insulin in both elderly and middle-aged patients with diabetes.
      Blunted insulin responses identify those patients who require insulin treatment,
      whereas high C-peptide values in insulin-treated patients suggest the possibility
      of discontinuing insulin therapy.

PMID- 15251538
TI  - Chlorpropamide-induced cholestatic liver failure resulting in death.
AB  - OBJECTIVE: To describe the first reported case of a death that occurred as a
      result of chlorpropamide-induced cholestatic liver disease. METHODS: We review
      the clinical and laboratory details of an 81-year-old man with type II diabetes
      mellitus, who was hospitalized because of nausea, vomiting, and jaundice.
      RESULTS: The patient had been taking a sulfonylurea (chlorpropamide, 250 mg
      orally three times a day) for 2 months. On initial assessment, the patient was
      noted to have cutaneous and scleral icterus and an erythematous maculopapular
      rash on the torso. The alkaline phosphatase level was substantially increased,
      and the transaminases were mildly increased. Use of all medications was
      discontinued. In the hospital, the patient's status rapidly deteriorated, and
      death ensued after cardiopulmonary arrest on day 6. CONCLUSION: The findings were
      consistent with a hypersensitivity reaction to chlorpropamide that ultimately
      resulted in fulminant cholestatic liver disease and death.

PMID- 15251539
TI  - Coding for endocrine services: using the new codes and the evocative/suppression
      testing protocols.
AB  - In 1994, a series of new current procedural terminology (CPT) codes for the
      description of services provided primarily by clinical endocrinologists were
      approved. Included were codes for 22 new endocrine evocative/suppression testing
      panels that represent the laboratory analyte portions of a series of endocrine
      protocols. These new codes were to be used in conjunction with another series of
      new codes for the physician's services, called prolonged physician services.
      These two new series of CPT codes are discussed in this article, and useful
      examples of their application, not described elsewhere to date, are provided.

PMID- 15251540
TI  - Parenteral nutrition formulation: an integral part of the endocrinologist's
      metabolic support consultation service.
AB  - Endocrinologists are uniquely suited to provide consultation in the new field of
      metabolic support. This specialty incorporates management of electrolyte and
      mineral disorders, diabetes mellitus, and malnutrition. Principles of formulation
      of parenteral nutrition are discussed, with an emphasis on distinguishing
      marasmus from kwashiorkor types of cachexia, disease-specific treatment,
      nutritional pharmacology, and relevant controversies.

PMID- 15251541
TI  - Intensive insulin therapy using twice-daily injections.

PMID- 15251542
TI  - Diabetic nephropathy--can it be prevented?

PMID- 15251543
TI  - Microalbuminuria in type II diabetes.
AB  - OBJECTIVE: To emphasize the prognostic significance of microalbuminuria in
      patients with type II diabetes and to summarize interventional studies in
      patients with non-insulin-dependent diabetes mellitus and nephropathy. METHODS:
      The definition of microalbuminuria is reviewed, the implications of its presence
      are discussed, and published trials of medical intervention to treat proteinuria
      in patients with type II diabetes are outlined. RESULTS: Microalbuminuria-
      defined as the presence of 30 to 300 mg of protein in a 24-hour urine specimen or
      a urinary albumin excretion rate of 20 to 200 mg/min--is frequently present in
      patients with non-insulin-dependent diabetes mellitus. It has been shown to be an
      independent cardiovascular risk factor as well as a predictor for the eventual
      development of renal failure. Intervention trials indicate that treatment with
      "tight" blood glucose control and antihypertensive agents, especially angiotensin
      converting enzyme inhibitors, may be beneficial in reversing early proteinuria or
      at least in preventing the progression to renal failure. CONCLUSION: The presence
      of microalbuminuria in patients with type II diabetes mellitus is associated with
      premature death from cardiovascular disease and the development of renal failure.
      Thus, aggressive therapy should be instituted.

PMID- 15251544
TI  - Prevention and treatment of diabetic nephropathy: role of angiotensin-converting
      enzyme inhibitors.
AB  - OBJECTIVE: To discuss the role of angiotensin-converting enzyme inhibitors in the
      management of diabetes-related renal disease. METHODS: We review the published
      data from animal studies and clinical trials and outline the adverse effects that
      may limit the use of these drugs. RESULTS: Diabetic nephropathy is the most
      common cause of end-stage renal disease and dialysis in the United States. With
      improving measures to optimize blood glucose control and blood pressure, the
      progression from mild proteinuria to overt renal insufficiency can now be
      retarded or even arrested. Studies of therapeutic interventions have shown that
      angiotensin-converting enzyme inhibitors have a superior beneficial effect on
      nephropathy. Few adverse effects are associated with use of these drugs: a
      nonproductive cough is the most frequent side effect, and angioedema and
      agranulocytosis are the most serious (albeit rarely reported) effects.
      CONCLUSION: Angiotensin-converting enzyme inhibitors should be considered as
      first-line therapy for patients with diabetes who have microalbuminuria or
      macroalbuminuria.

PMID- 15251545
TI  - Role of glycemic control and protein restriction in clinical management of
      diabetic kidney disease.
AB  - OBJECTIVE: To assess the role of control of blood glucose levels and restriction
      of dietary protein in the management of diabetic nephropathy. METHODS: We
      summarize the results of pertinent published studies of glycemic control and
      modification of protein intake to provide information about strategies that
      potentially could benefit patients with diabetes and renal dysfunction. RESULTS:
      Considerable evidence is available to support the contention that improved
      glycemic control may have beneficial effects on the development and progression
      of diabetic renal disease. Maximal benefits of improved glycemia occur when
      instituted before the onset of macroalbuminuria. Once overt diabetic nephropathy
      is established, improved glycemic control may not be beneficial. Current evidence
      indicates that a glycosylated hemoglobin level of less than 8.1% should be the
      glycemic goal. At this level, the risk of developing micro-albuminuria is
      substantially reduced, and the risk of hypoglycemia is minimized. Most studies
      have been conducted in type I diabetes, and the results have been extrapolated to
      type II diabetes. Whether improved glycemic control will be equally beneficial in
      the nephropathy of type II diabetes has yet to be determined. Although some
      scientific evidence supports dietary protein restriction in patients with
      diabetic nephropathy, the extent of restriction needed for optimal benefits and
      minimal side effects remains to be determined. On the basis of current
      information, patients with both types of diabetes who have evidence of
      nephropathy should have protein limited to the recommended dietary allowance for
      adults (0.8 g/kg of body weight per day or approximately 10% of total daily
      caloric intake), and protein should be derived primarily from vegetable and lean
      animal sources. CONCLUSION: End-stage renal disease is not inevitable in patients
      with diabetic nephropathy. Normalization of glucose levels and modification of
      protein intake can favorably influence the course of diabetes-related kidney
      disease.

PMID- 15251546
TI  - Reversible thioridazine-induced magnetic resonance imaging-documented pituitary
      enlargement associated with hyperprolactinemia.
AB  - OBJECTIVE: To document a case of reversible thioridazine-induced pituitary
      enlargement associated with hyperprolactinemia in a patient with schizophrenia.
      METHODS: We describe a 19-year-old woman with paranoid schizophrenia who was
      taking thioridazine (a phenothiazine), in whom hyperprolactinemia, galactorrhea,
      oligomenorrhea, and a reversible anatomic pituitary abnormality developed. Serial
      magnetic resonance imaging (MRI) studies were used to assess the status of the
      pituitary gland during various pharmaceutical therapies. RESULTS: Laboratory
      evaluation revealed increased serum prolactin (PRL) levels that ranged from 76 to
      135 mg/L. Results of thyroid function tests were normal, and gonadotropins and
      estradiol levels were low, consistent with hyperprolactinemia. MRI revealed
      asymmetric enlargement of the right side of the pituitary gland. Discontinuing
      the thioridazine therapy resulted in normalization of the serum PRL and
      resolution of the pituitary abnormality. Subsequent worsening of the patient's
      psychiatric condition necessitated a course of electroconvulsive therapy and
      initiation of treatment with clozapine, a D4 dopamine receptor antagonist. At 1
      year follow-up, at which time the patient was maintained on clozapine and was not
      taking thioridazine, both serum PRL levels and MRI findings remained normal.
      CONCLUSION: Our patient was shown to have asymmetric pituitary enlargement
      associated with thioridazine-induced hyperprolactinemia, which reversed when use
      of the drug was discontinued. In patients with serum PRL levels in excess of 100
      mg/L during antipsychotic drug therapy, evaluation for a prolactinoma is
      warranted.

PMID- 15251547
TI  - Androstenedione aromatization as a cause of gynecomastia in 11beta-hydroxylase
      and 21-hydroxylase deficiencies.
AB  - OBJECTIVE: To report two cases of gynecomastia that occurred in boys with 11beta
      hydroxylase and 21-hydroxylase deficiency. METHODS: We describe the physical
      findings and summarize the laboratory evaluation and treatment of two cases
      encountered in our medical practice. RESULTS: Both of our patients (a 4-year-old
      boy and a 17-year-old boy) had extreme virilization and gynecomastia; on
      laboratory assessment, androstenedione and estrogen levels were high. Treatment
      with hydrocortisone was recommended. CONCLUSION: Peripheral conversion of adrenal
      androgen to estrogen likely caused the feminizing syndrome in these patients.

PMID- 15251548
TI  - Frasier syndrome.
AB  - OBJECTIVE: To present the case of a 17-year-old girl with primary amenorrhea and
      a history of hypertension since age 13 years. METHODS: The patient's clinical,
      laboratory, and radiologic data were summarized, and features of Frasier syndrome
      and Drash syndrome were compared. RESULTS: The patient's weight was 126 kg,
      height was 185 cm, and blood pressure was 150/100 mm Hg. She had minimal breast
      budding and scant pubic hair. Laboratory data were compatible with
      hypergonadotropic hypogonadism. An ultrasound study of the pelvis revealed an
      infantile uterus and a questionable right gonad. The patient also had nephrotic
      range proteinuria in conjunction with decreased creatinine clearance and normal
      findings on ultrasonography of the kidneys. A karyotype photomicrograph showed a
      male 46,XY chromosomal pattern. Although the patient's chronologic age was 17
      years, her bone age was 12 1/2 years. CONCLUSION: The patient was diagnosed as
      having Frasier syndrome. She underwent removal of a left-sided ovary and a right
      adnexal mass, and her condition is well controlled with lisinopril (10 mg daily)
      and estrogen therapy.

PMID- 15251549
TI  - Association of cardiac autonomic neuropathy and microalbuminuria in non-insulin
      dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate the relationship between microalbuminuria and autonomic
      neuropathy in diabetes mellitus. METHODS: A consecutive series of 151 patients
      with non-insulin-dependent diabetes mellitus underwent assessment in a single
      medical practice during a 3 1/2-year period for the presence of microalbuminuria
      and cardiac autonomic neuropathy. On the basis of microalbuminuria, the patients
      were categorized into two groups for comparison. RESULTS: Of the overall group of
      151 patients, 91 had increased urinary albumin (50 mg/L or more), and 60 had
      normal albumin excretion (20 mg/L or less). Cardiac autonomic neuropathy was
      detected in 54% of the former group and 35% of the latter group. Thus, the
      presence of microalbuminuria was highly associated with cardiac autonomic
      neuropathy (results of chi2 analysis were significant at 2.3%). Other factors-
      duration of diabetes, blood pressure, and serum cholesterol and creatinine levels
      -did not differ between the two study groups. CONCLUSION: Results of this study
      indicate that the incidence of cardiac autonomic neuropathy is higher in those
      patients with increased urinary albumin levels than in those with normal
      excretion of albumin.

PMID- 15251550
TI  - Coexistence of diabetes and phosphofructokinase deficiency.
AB  - OBJECTIVE: To report the first case of coexisting diabetes mellitus and
      phosphofructokinase deficiency. METHODS: We describe a 50-year-old woman who had
      a history of diabetes mellitus, muscle weakness, and mild hemolysis.
      Phosphofructokinase deficiency was diagnosed with use of the ischemic forearm
      exercise test and magnetic resonance spectroscopy during exercise. RESULTS: The
      presence of phosphofructokinase deficiency affected the methods of follow-up and
      choices of diabetes therapy. Insulin therapy was avoided because insulin may
      exacerbate muscle weakness by suppressing production of free fatty acids.
      Strenuous exercise had to be avoided as well because it may induce myoglobinuria
      in patients with phosphofructokinase deficiency. Glycosylated hemoglobin
      measurements could not be used because they were falsely low (from hemolysis),
      and other indicators of long-term glycemic control were utilized instead.
      CONCLUSION: Diabetes mellitus and phosphofructokinase deficiency can coexist. In
      such cases, choices of diabetes therapy and methods of monitoring of glycemic
      control must be adjusted to account for the presence of phosphofructokinase
      deficiency.

PMID- 15251551
TI  - Lithium therapy and disorders of the parathyroid glands.
AB  - OBJECTIVE: To review the effects of lithium (Li+) on the parathyroid glands.
      METHODS: We describe the incidence and clinical features of Li(+)-associated
      hyperparathyroidism and summarize the current state of knowledge of the in vitro
      and in vivo effects of Li+ on the parathyroid cell. RESULTS: Li+ treatment is
      known to increase the calcium set-point in the parathyroid glands for inhibition
      of parathyroid hormone secretion. Evidence suggests that this change in calcium
      set-point occurs as a result of Li+ interference with transmembrane signal
      transduction in the parathyroid cell. Li+ therapy may accentuate the set-point
      error in patients with primary hyperparathyroidism and unmask preexisting
      hyperplastic or adenomatous changes in the parathyroid glands. Li+ may also cause
      de novo hypercalcemia and hyperparathyroidism that are usually mild, clinically
      insignificant, and reversible with discontinuation of Li+ therapy. In some
      patients receiving long-term Li+ therapy, however, persistent hyperparathyroidism
      develops despite discontinuation of Li+ therapy, and it may be symptomatic and
      associated with serious organ system sequelae. Li(+)-associated hypercalcemia can
      be a challenging clinical dilemma in patients with bipolar affective disorder
      because of the lack of effective therapeutic alternatives, as well as the
      potential for Li(+)-induced hypercalcemia to exacerbate psychopathologic
      symptoms. CONCLUSION: Because severe hypercalcemia may occur as a result of toxic
      Li+ levels, Li+ and calcium levels should be monitored in patients on long-term
      Li+ therapy.

PMID- 15251552
TI  - Coding: the history of the recognition of endocrinology services.
AB  - Until recent years, endocrinology services were reimbursed with the use of
      generic codes. Efforts to establish codes specifically for endocrinology tests,
      protocols, and services during the past 12 years are reviewed. The formation of
      the American Association of Clinical Endocrinologists and the involvement of
      their membership on behalf of clinical endocrinology are detailed. Presentation
      of three complex coding challenges exemplifies the need for ongoing efforts to
      improve and update endocrinology codes.

PMID- 15251553
TI  - Rationale for prevention and treatment of glucose-mediated macrosomia: a protocol
      for gestational diabetes.
AB  - OBJECTIVE: To formulate a rationale for preventing and treating hyperglycemia
      during pregnancy and the concomitant risk of macrosomia. METHODS: We reviewed
      pertinent studies in the literature and personal experience with patients who had
      gestational diabetes. In addition, dietary and exercise interventions in the
      management of such patients were assessed. RESULTS: During pregnancy, sequential
      hormonal increases occur to provide glucose substrate to the fetus. When a
      pregnant woman has a limited insulin secretory capacity and cannot produce enough
      insulin to compensate for the effect of diabetogenic hormones, gestational
      diabetes occurs (usually during the second trimester). Maternal hyperglycemia
      reportedly increases fetal secretion of insulin, and fetal hyperinsulinemia may
      predispose the fetus to macrosomia. Thus, metabolic abnormalities associated with
      diabetes during pregnancy result in long-term effects on the offspring, including
      insulin resistance, obesity, and diabetes, which in turn may contribute to
      transmission of risk for development of the same problems in subsequent
      generations. Insulin therapy, dietary measures, and exercise have helped to
      achieve euglycemia in patients with gestational diabetes. CONCLUSION: Universal
      screening for gestational diabetes is optimally performed at 26 weeks of
      gestation. Treatment of diagnosed cases, by insulin, diet, and exercise regimens,
      will decrease the occurrence of glucose-related macrosomia, improve the outcome
      of the pregnancy, and reduce the risks for obesity, hypertension, and diabetes in
      future progeny.

PMID- 15251554
TI  - The art and science of maintenance of normoglycemia in pregnancies complicated by
      insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To provide a "how-to" manual for achieving and maintaining
      normoglycemia in pregnant women with insulin-dependent diabetes. METHODS: We
      describe a detailed program that has successfully maintained normoglycemia
      before, during, and after diabetes-complicated pregnancies. Insulin and glucose
      requirements throughout pregnancy, during labor, and in the postpartum period are
      outlined. RESULTS: With preconception planning and careful dietary and blood
      glucose management during pregnancy, complications can be minimized and an
      optimal outcome of pregnancy can be achieved in women with diabetes. CONCLUSION:
      Women with type I, insulin-dependent diabetes can now have the same chances as
      women without diabetes to have a healthy infant. The reduction of risks
      associated with pregnancies complicated by diabetes can be ensured if
      normoglycemia is achieved before and during the pregnancy.

PMID- 15251555
TI  - Correlations of plasma concentrations of B-cell polypeptides with pathologic
      features of insulinomas.
AB  - OBJECTIVE: To assess the correlations between plasma concentrations of b-cell
      polypeptides (insulin, C peptide) and size, multiplicity, and malignancy of
      insulinomas. METHODS: We retrospectively reviewed the medical records of 55
      consecutively treated patients at our institution with surgically confirmed
      insulinoma. The 29 female and 26 male patients ranged from 13 to 77 years of age
      (median, 46). Plasma insulin, C peptide, proinsulin, and glucose concentrations
      were analyzed statistically in patients with benign and those with malignant
      insulinomas. RESULTS: Significant correlations were observed between plasma
      insulin and tumor size (r = 0.45; P = 0.001) and tumor volume (r = 0.41; P =
      0.007) and between plasma C peptide and tumor size (r = 0.38; P = 0.004) and
      tumor volume (r = 0.33; P = 0.025). No differences between benign and malignant
      tumors were noted for plasma insulin, C peptide, glucose, nor tumor size or
      volume. No correlations were found between plasma insulin, C peptide, or glucose
      and number of tumors. CONCLUSION: The plasma levels of insulin and C peptide
      provide qualitative indications about the size of insulinomas.

PMID- 15251556
TI  - Hypogonadism and methadone: Hypothalamic hypogonadism after long-term use of high
      dose methadone.
AB  - OBJECTIVE: To assess the relationship between hypogonadism and long-term
      administration of high-dose methadone. METHODS: We present a case of a 47-year
      old man with a history of heroin use and treatment with high doses of methadone
      (130 mg/day), who complained of gynecomastia and impotence. Baseline levels of
      serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), plasma
      testosterone, and prolactin were determined, and then the response of
      gonadotropin levels to stimulation with gonadotropin-releasing hormone (GnRH) was
      examined at 30, 60, 90, 120, and 180 minutes. RESULTS: Basal values of
      testosterone, LH, and FSH were below normal levels, whereas prolactin was normal.
      After administration of GnRH, the patient had a suboptimal increase in LH levels
      and lack of a response of FSH. When the daily dose of methadone was decreased to
      40 mg, the patient's libido returned, and LH, FSH, and testosterone levels
      increased. CONCLUSION: These findings could indicate the presence of (1) a direct
      effect of methadone on the hypothalamus that leads to an alteration in normal
      gonadotropin pulse patterns, or (2) a selective effect of methadone on the
      anterior pituitary that alters its response to GnRH, with either mechanism
      leading to a reversible, dose-related depression of testosterone levels.

PMID- 15251557
TI  - Effective use of magnetic resonance imaging in the assessment of children with
      possible growth hormone deficiency.
AB  - OBJECTIVE: To present our experience with diagnosis of growth hormone (GH)
      deficiency in children and to determine which patients are most likely to benefit
      from magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed
      medical records of pediatric patients who underwent assessment for possible GH
      deficiency during a 6-year period and correlated clinical variables, stimulated
      GH responses, and MRI findings. RESULTS: Of 100 children who failed outpatient GH
      screening tests, 14 were classified as at risk for hypothalamic pituitary
      defects, and 86 were considered not at risk, having short stature only. Patients
      were further stratified by age, sex, growth variables, maximal GH response to
      provocative testing, and MRI findings. A significant relationship existed between
      the presence of risk factors, maximal GH of <5 mg/L, and sellar defects. With no
      risk factors, MRI scans showed normal findings in 15 of 17 patients with maximal
      GH of <5 mg/L, in 33 of 34 patients with GH between 5 and 10 mg/L, and in all 35
      patients with GH of >10 mg/L. Abnormal MRI findings included posterior pituitary
      ectopy, decreased pituitary size, absent midline central nervous system
      structures, enlarged infundibulum, and hamartoma. In one child with a 4-year
      history of growth failure and a maximal GH of 3.5 mg/L, craniopharyngioma was
      diagnosed. CONCLUSION: MRI scans should be obtained in any child with multiple
      pituitary hormone deficiencies, hypoglycemia, ophthalmologic anomalies, low
      stimulated GH, or acquired growth failure. Otherwise asymptomatic children with
      growth delay and maximal GH of >10 mg/L do not need routine MRI screening. Such a
      strategy could result in substantial cost savings.

PMID- 15251558
TI  - Biochemical studies in the evaluation and management of osteoporosis: current
      status and future prospects.
AB  - OBJECTIVE: To examine the current status of biochemical markers of bone
      remodeling and to offer a perspective on their future clinical applications.
      METHODS: We provide a comprehensive overview of the bone remodeling cycle, the
      hormonal control of bone remodeling, the specific biochemical markers of bone
      resorption and bone formation, and their current clinical applications. RESULTS:
      Bone remodeling occurs in discrete packets, known as bone modeling units, on the
      surfaces of the skeleton. Osteoclasts are responsible for bone resorption, and
      osteoblasts are responsible for bone formation. Bone resorption and formation are
      normally coupled, and an imbalance in these processes can lead to metabolic bone
      diseases such as osteoporosis. Investigators have attempted to measure various
      biochemical markers of bone resorption (such as urine calcium and hydroxyproline)
      and formation (such as bone-specific alkaline phosphatase and osteocalcin) as a
      reflection of response to therapy. Although several markers of bone resorption
      and formation can be assayed, an ideal marker has yet to be discovered or proved.
      CONCLUSION: Until a precise, inexpensive assay is developed, currently available
      biochemical markers, used in conjunction with measurements of bone density, are
      considered the most reasonable tools for classifying and directing the management
      of osteoporosis.

PMID- 15251559
TI  - Treatment of dyslipidemias.
AB  - OBJECTIVE: To summarize recommended treatment strategies for various
      dyslipidemias. METHODS: The basic pathways of lipoprotein metabolism are
      reviewed, and the potential for interventional alterations to correct specific
      dyslipidemias is outlined. Guidelines for treatment based on published clinical
      trials, including the consensus report of the National Cholesterol Education
      Program, are discussed. RESULTS: The nonpharmacologic options of diet and
      exercise are important elements in the treatment of dyslipidemias. In most
      patients, a reduced dietary intake of fat (particularly saturated fat) should be
      maintained for 3 months before drug therapy is initiated. The various mechanisms
      of action of the bile acid resins, niacin, hydroxy-methylglutaryl-coenzyme A
      reductase inhibitors, and fibric acid derivatives are described, and their roles
      in monotherapy or combination therapy for hypercholesterolemia, combined
      hyperlipidemia, and hypertriglyceridemia are examined. CONCLUSION: With an
      understanding of the metabolic pathways responsible for the production and
      removal of lipoproteins and an overview of results of previous pharmacologic
      interventions, clinicians can optimize lipid-lowering treatment in individual
      patients with dyslipidemia.

PMID- 15251560
TI  - Gene therapy and inherited dyslipidemia.
AB  - OBJECTIVE: To explore the current status and future potential of gene therapy for
      the inherited dyslipidemias. METHODS: A brief overview of the inherited
      dyslipidemias, a review of the currently available means of transferring genetic
      material in vivo, and a discussion of two examples of conditions in which gene
      therapy may be useful--familial hypercholesterolemia and reduced high-density
      lipoprotein cholesterol syndromes--are presented. RESULTS: Although substantial
      progress has been made in the management of inherited dyslipidemia, optimal
      treatment regimens are not available in all cases. Gene therapy has recently
      emerged as a potential solution to some of these problems. For gene therapy to be
      successful, several factors are necessary: an efficient means of gene transfer,
      long-term transgene expression, and lack of toxicity. Although the feasibility of
      this approach has been demonstrated, currently available vectors have a number of
      technical and safety limitations. CONCLUSION: Gene therapy for inherited
      dyslipidemias has many technical hurdles that must be overcome before it will
      have widespread clinical application.

PMID- 15251561
TI  - Nonthyroidal illness syndrome or euthyroid sick syndrome?
AB  - OBJECTIVE: To characterize the nonthyroidal illness syndrome (NTIS) and to
      discuss various underlying potential biochemical mechanisms for this condition.
      METHODS: The pertinent medical literature was reviewed, and studies of thyroid
      function in systemic non-thyroidal illnesses were summarized. RESULTS:
      Abnormalities of thyroid function in the NTIS have been classified into four
      major categories: (1) low triiodothyronine (T3) syndrome, (2) a combination of
      low T3 and low thyroxine (T4), (3) high T4 syndrome, and (4) other abnormalities.
      The NTIS has been noted in essentially all severe systemic illnesses and after
      caloric deprivation, major operations, and administration of some drugs. Some
      mechanisms that may contribute to low serum T3 in the NTIS are decreased type I 5
      -monodeiodinase in tissues, decreased uptake of T4 by tissues, decreased serum
      binding, increased reverse T3, alterations in selenium status, cytokines, and a
      decrease in thyrotropin. Decreased thyrotropin may also contribute to low T4
      levels in NTIS, as may decreased serum T4-binding proteins, abnormalities in T4
      binding globulin, and circulating inhibitors of binding of T4 to serum proteins.
      Although T4 treatment of patients with NTIS has yielded little improvement,
      administration of T3 has produced some beneficial effects. CONCLUSION: Further
      studies should be conducted to determine appropriate patient populations, dose
      response ratios, and possible adverse effects of treatment of the NTIS with T3.

PMID- 15251562
TI  - Autoimmune thyroid disease in pregnant women and their offspring.
AB  - OBJECTIVE: To present an overview of autoimmune thyroid disease (AITD) that can
      occur in pregnancy. METHODS: The major thyroid antibodies that can traverse the
      maternal-fetal circulation and affect the fetus are summarized, those women at
      risk of having affected fetuses are identified, and the diagnosis, course, and
      treatment of AITD in maternal and neonatal patients are discussed. SUMMARY: AITD,
      including Graves' disease and autoimmune thyroiditis, is common in women of
      childbearing age. Rarely, the fetus can be affected because of transplacental
      passage of maternal IgG. Of the thyroid autoantibodies found in AITD, only those
      directed against the thyroid-stimulating hormone (TSH) receptor have been shown
      to cause fetal thyroid dysfunction. Both transient neonatal hyperthyroidism and
      hypothyroidism have been described, as has delayed onset of neonatal
      hyperthyroidism due to the coexistence of stimulating and blocking TSH receptor
      antibodies. In general, affected infants are those born to mothers with the most
      potent antibody activity, and the duration of the neonatal thyroid dysfunction is
      dependent on the antibody titer and the rate of metabolic clearance from the
      infant's circulation. If fetal hyperthyroidism is suspected, maternal TSH
      receptor antibodies should be measured during the third trimester of pregnancy.
      For neonatal hypothyroidism, this measurement in the mother or baby soon after
      birth will suffice. Screening for the presence of TSH receptor antibodies by
      radioreceptor assay is the most cost-effective approach. If results are positive,
      bioassay should be done to determine the nature of the antibody activity. Women
      at risk of having babies with neonatal hyperthyroidism include those with a
      history of previous affected infants, with difficult to control thyrotoxicosis,
      or with a history of Graves' disease and development of hypothyroidism either
      spontaneously or as a result of thyroid gland ablation. Transient neonatal
      hypothyroidism due to TSH receptor-blocking antibodies should be suspected in any
      infant with hypothyroidism born to a mother with AITD (particularly those with
      previously affected offspring). CONCLUSION: Treatment of maternal hyperthyroidism
      must consider both maternal and fetal thyroid status. In general, the lowest dose
      of antithyroid medication sufficient to produce maternal euthyroidism or slight
      hyperthyroidism is used. In pregnant women with hypothyroidism, doses of L
      thyroxine should be sufficient to normalize maternal thyroid function without
      regard to the fetus. Identification and treatment of affected infants soon after
      birth will ensure a normal outcome. Whether inadequately treated maternal
      hypothyroidism is associated with a permanent intellectual deficit in the
      offspring is currently unknown.

PMID- 15251563
TI  - Insulin requirements in 242 patients with type II diabetes mellitus.
AB  - The purpose of this study was to determine the subcutaneous insulin requirements
      for rapid, effective regulation of blood glucose in patients with poorly
      controlled type II diabetes mellitus by using an intravenous insulin infusion
      protocol. The insulin infusion achieved a mean (+/-SD) overnight blood glucose
      concentration of 101 +/- 15 mg/dL and 24-hour glucose concentration of 118 +/- 18
      mg/dL. The intravenous insulin requirement of 81 +/- 32 U/day correlated well
      (P<0.001) with the subsequent subcutaneous insulin requirement of 84 +/- 43 U/day
      necessary to maintain preprandial glucose values of 112 +/- 15 mg/dL. Insulin
      requirements ranged from 0.2 to 2.0 U/kg per day (95% confidence interval, 0.4 to
      1.6). Weaker correlations were noted between total insulin requirements and
      weight (r = 0.60) or body mass index (r = 0.57); no correlations were observed
      with age, duration of diabetes, or antecedent glycemic control as reflected by
      glycosylated hemoglobin values. These findings may be useful for initiating
      insulin treatment on an ambulatory basis.

PMID- 15251564
TI  - Pseudohypercalcemia in an elderly patient with multiple myeloma: report of a case
      and review of literature.
AB  - Hypercalcemia, a common complication of multiple myeloma, is primarily caused by
      increased bone resorption. The increase in total calcium is usually associated
      with an increase in the ionized calcium (Ca(I)), and the hypercalcemia is
      frequently symptomatic. Rarely, pseudohypercalcemia in multiple myeloma is caused
      by binding of calcium to the abnormal immunoglobulin. In this setting, the Ca(I)
      is normal. We describe a 90-year-old woman with an IgA-k myeloma who had
      substantial increases in the total calcium but normal levels of Ca(I). Clinicians
      should recognize this unusual phenomenon to avoid unnecessary and potentially
      toxic therapy.

PMID- 15251565
TI  - Nondiabetic neuropathy in a patient with diabetes.
AB  - A case of peripheral neuropathy in a patient with diabetes who had atypical
      clinical findings is presented. Because of the atypical initial manifestations
      and short duration of insulin-dependent diabetes, another cause of the neuropathy
      was suspected. The presence of vitiligo, hypothyroidism, and diabetes prompted a
      search for evidence of pernicious anemia. Despite a normal blood cell count, the
      diagnosis of pernicious anemia was confirmed on the basis of an increased serum
      gastrin level and antiparietal cell antibody titer. Treatment with vitamin B12
      resulted in an arrest, but not a reversal, of the signs of peripheral neuropathy.
      In patients with diabetes, vitamin B12 deficiency should be suspected; its early
      diagnosis and treatment are important in minimizing neurologic damage.

PMID- 15251566
TI  - Syndrome of type II polyglandular autoimmunity associated with HLA-DR4 in a large
      kindred, including HLA-DR3/DR4 heterozygosity in the probands, identical twins
      with identical manifestations.
AB  - Autoimmune destruction and resultant failure of multiple organ systems constitute
      an uncommon entity known as type II polyglandular failure. Occasionally, the
      syndrome is familial, and in the kindreds studied, individual patients have
      manifested different sets of the associated diseases. We describe a large family
      in which the presence of HLA-DR4 was associated with development of this
      syndrome. More commonly, HLA-DR3 has been associated with type II polyglandular
      failure. The probands are monozygotic twin sisters in whom an identical set of
      autoimmune diseases occurred in the same order of onset and at approximately the
      same age. These data suggest that not only do specific factors predispose to this
      syndrome but also distinct factors determine which individual diseases are
      expressed.

PMID- 15251567
TI  - Hospitalization of patients with diabetes.
AB  - To determine annual hospitalization rates for patients with diabetes mellitus, we
      retrospectively analyzed the frequency of hospitalization among 905 patients with
      diabetes receiving primary care in a private practice outpatient program during a
      20-month period (1,508 patient-years). We assessed the annual hospitalization
      rates stratified by diabetes clinical severity index, type of diabetes, type of
      treatment, age, sex, and mean glycosylated hemoglobin. The all-cause annual
      hospitalization rate was 211 per 1,000 patients (95% confidence interval, 184 to
      238). Hospitalization rates were strongly correlated with measures of clinical
      severity; hospitalization rates did not vary significantly with type of diabetes,
      age, or sex. Among patients with type II diabetes, rates were higher in the group
      treated with insulin. A trend was noted for hospitalization rates to increase
      with mean glycosylated hemoglobin (not statistically significant in this sample).
      Overall, 14% of hospitalizations were for metabolic reasons, 45% were related to
      clinical complications of diabetes, and 41% were unrelated to the presence of
      diabetes. In analysis of hospitalization rates and therefore health-care
      expenditures for patients with diabetes, the characteristics of the patient
      population--and especially measures of clinical severity--must be considered.
      Interventions to reduce hospitalization can be targeted at high-risk groups.

PMID- 15251568
TI  - Thyroid hormone excess and bone--a clinical review.
AB  - During the past several years, studies have suggested that exogenous thyroid
      hormone may adversely affect bone. In order to address this contention and to put
      the issue in perspective for clinicians who treat patients with thyroid hormone
      replacement, the available literature was reviewed, and the various study
      populations were characterized. Age, gender, and menopausal status of the patient
      are important factors, as are the indication for thyroid hormone replacement and
      the extent, duration, and severity of prior hyperthyroidism. Reliable measures of
      bone mineral density, particularly dual-energy x-ray, absorptiometry have become
      available, providing a more accurate reflection of this parameter in patients
      receiving thyroxine therapy in comparison with control subjects. The bulk of
      evidence indicates that long-term thyroxine therapy is safe if the dose is
      carefully monitored. Treatment with thyroxine does not produce clinically
      significant bone disease.

PMID- 15251569
TI  - Fine-needle aspiration biopsy of thyroid nodules.
AB  - Nodular thyroid disease is a common problem, particularly in women and the
      elderly population. Furthermore, 5% of thyroid nodules are likely to be
      malignant. Therefore, assessment for malignant potential is important, and fine
      needle aspiration (FNA) biopsy is the most accurate technique. For each nodule,
      two to four aspirations should be attempted from different areas of the nodule.
      Although major complications of FNA biopsy are rare, proper cytologic
      interpretation necessitates special expertise. Cytologic diagnoses are usually
      categorized as diagnostic or nondiagnostic, and the diagnostic specimens are
      classified as benign, "suspicious," or malignant. Rebiopsy is indicated for
      enlarging nodules, recurrent cysts, and nondiagnostic cytologic findings. Because
      FNA biopsy is a safe, reliable, and rapid means of evaluating thyroid nodules, we
      recommend its routine use for diagnosis and treatment of thyroid nodular disease.

PMID- 15251570
TI  - Metformin: actions and indications for use in non-insulin-dependent diabetes
      mellitus.
AB  - Metformin (N,N-dimethylbiguanide) is about to be introduced into the United
      States. The drug, a potent blood glucose-lowering agent, is rapidly absorbed
      through the small intestine, has a circulating t 1/2 in plasma of 1.7 to 2.5
      hours, and is 90% cleared through the kidneys in 12 hours. The drug does not
      cause hypoglycemia in nondiabetic patients and is effective in both obese and
      nonobese patients with non-insulin-dependent diabetes mellitus (NIDDM). The drug
      does not act through stimulation of endogenous insulin secretion. It seems to act
      at multiple sites, with a small effect on the inhibition of intestinal glucose
      transport, a moderate effect on inhibition of hepatic glucose output, and a major
      effect on enhancement of peripheral glucose uptake by muscle and adipose tissues.
      In addition to its glucose-lowering potency, metformin causes weight loss in
      obese patients with NIDDM and lowers total cholesterol, very-low-density
      lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein
      triglyceride levels as well as causing an increase in high-density lipoprotein
      cholesterol level. The drug is ideally suited for obese patients with NIDDM who
      are unresponsive to diet alone, and it is effective in combination with
      sulfonylureas. The major risk associated with use of metformin is the development
      of lactic acidosis. Patients predisposed toward the development of lactic
      acidosis are those with hepatic or renal disease or with tissue ischemia, in whom
      the drug should not be prescribed.

PMID- 15251571
TI  - Overview of lipoprotein metabolism: mechanisms involved and conveying this
      information to patients.
AB  - The major classes of lipoprotein particles are chylomicrons, very-low-density
      lipoproteins, low-density lipoproteins, and high-density lipoproteins. Each of
      these particles has distinct characteristics, including a distinct apolipoprotein
      composition. The basic functions of these major apolipoproteins are briefly
      summarized for clinicians, and disorders of lipoprotein metabolism are discussed.
      For the effective management of lipid disorders, the therapy should be tailored
      to the specific defect. Compliance may be improved if the patient understands the
      nature of the particular lipid problem. To that end, we have developed an analogy
      in which the various classes of lipoprotein particles are equated to different
      trucking systems, and the liver is considered a warehouse for storage and
      distribution of fat. With use of this explanation, patients may understand the
      rationale for selection of various therapeutic strategies, and treatment of the
      hyper-lipoproteinemia is likely to be more successful.

PMID- 15251572
TI  - Dyslipidemia and diabetes: a personal view.
AB  - Cardiovascular disease, the main cause of morbidity and mortality in patients
      with diabetes, justifies an aggressive approach to the reduction of modifiable
      risk factors. Lipid values are generally normal in patients with insulin
      dependent diabetes mellitus, but hypertriglyceridemia and low levels of high
      density lipoprotein (HDL) cholesterol are frequently associated with non-insulin
      dependent diabetes mellitus (NIDDM). Recommendations for screening and treatment
      of patients without diabetes do not apply to those with NIDDM. Screening should
      be done annually and should include fasting total cholesterol, triglycerides, and
      HDL cholesterol. Therapeutic recommendations based solely on the low-density
      lipoprotein cholesterol level are inappropriate. Hypertriglyceridemia cannot be
      ignored in patients with NIDDM. Therapy should first be directed toward improved
      control of the diabetes through diet, exercise, and insulin or sulfonylureas.
      Therapeutic goals are selected on the basis of individual risk assessment and are
      strongly influenced by the presence of preexisting vascular disease. When the
      goals are not achieved through improved control of diabetes, lipid-lowering drug
      therapy, based on the specific profile of the lipid abnormalities, should be
      initiated.

PMID- 15251573
TI  - Human Lp(a): regions in sequences of apoproteins similar to domains in signal
      transduction proteins.
AB  - The major apoproteins of Lp(a)--apo(a) and apo B-100--are linked by only one
      intermolecular disulfide bond. This linkage has been suggested to be located
      between apo(a) Cys4057 and apo B-100 Cys3734. Several studies, however, have
      suggested other noncovalent interactions between different regions of apo(a) and
      apo B-100. One possible mechanism for these interactions may involve the apo(a)
      proline-rich interkringle regions that share sequence similarities with the
      proline-rich regions of Src homology 3 (SH3) domain-binding proteins such as 3BP
      1. SH3 and SH2 domains, and their respective ligands, proline-rich regions, and
      phosphotyrosine motifs, are noncatalytic segments common to signal transduction
      proteins. Therefore, we used sequence comparison algorithms and molecular
      modeling programs to identify corresponding SH3 and SH2 candidate regions as well
      as potential phosphotyrosine sites in the apo B-100 sequence. Six SH2 and 16 SH3
      candidate regions, along with 21 potential phosphotyrosine sites, are contained
      in the apo B-100 sequence. In Lp(a), these regions of apo B-100 may be involved
      in the noncovalent, protein-protein interactions between apo(a) and apo B-100.
      The presence of candidate SH3 and SH2 regions in apo B-100, and potential
      phosphotyrosine sites in apo B-100, apo(a), and apo A-I, suggests an alternative
      signaling pathway unrelated to the known B/E receptor.

PMID- 15251574
TI  - Bioassayable and immunoassayable prolactin responses to thyrotropin-releasing
      hormone: use of the Nb2 lymphoma cell bioassay.
AB  - The peak prolactin response to thyrotropin-releasing hormone (TRH) varies among
      patients. "Exaggerated" responses have been described and linked to ovulatory
      dysfunction. Herein we describe our initial observations on bioassayable
      prolactin (BA-PRL) versus immunoassayable prolactin (RIA-PRL) in women with
      normal baseline RIA-PRL concentrations but with varying peak RIA-PRL responses to
      TRH. Twenty-three women of reproductive age with baseline RIA-PRL of =25 ng/mL
      were administered 500 microg of TRH, and baseline and peak RIA-PRL concentrations
      were determined. Aliquots of the baseline sample and the sample representing the
      peak RIA-PRL were used for measuring BA-PRL by means of the Nb2 lymphoma cell
      bioassay. For each sample, BA/RIA-PRL ratios were determined. Positive
      correlations were found between peak RIA-PRL and baseline BA/RIA-PRL ratios
      (P<0.05) and also between baseline and peak BA/RIA-PRL ratios (P<0.001). Negative
      correlations were found between baseline RIA-PRL and both baseline and peak
      BA/RIA-PRL ratios (P<0.001 and P<0.05, respectively). We conclude that (1) the
      lactotroph response to TRH in women with normal RIA-PRL may, in part, be governed
      by the amount of biologically active prolactin at baseline and (2) the relative
      proportion of BA-PRL to RIA-PRL produced at baseline is maintained at peak
      response. Finally, in light of the greater availability of bioactive prolactin in
      women with exaggerated TRH responses, our findings support the use of
      bromocriptine in those patients with such responses and ovulatory dysfunction.

PMID- 15251575
TI  - Diabetes insipidus and histiocytosis X: a case of isolated pituitary involvement.
AB  - Diabetes insipidus is associated with histiocytosis X in approximately 50% of
      cases with multiple lesions that involve both intracranial and extracranial
      structures. Although approximately 8% of cases of diabetes insipidus in children
      are caused by involvement of the hypothalamus or pituitary infundibulum (or both)
      by histiocytosis X, diabetes insipidus can be the initial manifestation in many
      disorders most commonly, intracranial neoplasms. Herein we report a case of
      isolated histiocytosis X of the pituitary gland in a child for whom medical
      assistance was sought because of symptoms of diabetes insipidus.

PMID- 15251576
TI  - Transient hypopituitarism.
AB  - Spontaneous recovery of pituitary function in patients with hypopituitarism is
      rare. We report the case of a 30-year-old man in whom hypopituitarism and sudden
      onset of bilateral hearing loss developed after a viral infection. No evidence of
      a mass lesion was detected on computed tomography or magnetic resonance imaging
      of the pituitary gland. The patient received a 3-week course of treatment with a
      high dose of glucocorticoids; in a period of 6 weeks, he felt clinically well,
      and biochemical tests showed spontaneous return of normal anterior pituitary
      function. We speculate that an immune response triggered by the viral infection
      initiated an inflammatory process that involved the hypothalamus or pituitary
      gland and caused the hypopituitarism. The treatment with high-dose
      glucocorticoids could have prompted the resolution of the hypothalamic-pituitary
      inflammatory process and facilitated spontaneous recovery of pituitary function.
      This case shows that hypopituitarism may be transient an outcome that should be
      considered in patients with idiopathic hypopituitarism.

PMID- 15251577
TI  - A randomized comparison of the effect of two diuretics, a converting enzyme
      inhibitor, and a sympathomimetic amine on weight loss in diet-refractory
      patients.
AB  - We hypothesized that women refractory to dietary weight loss may have a type of
      idiopathic edema. In a study of 200 women, we compared four drugs, used
      previously for treating idiopathic edema, to determine their efficacy in causing
      weight reduction. After 6 months of treatment, the percentage of treated groups
      losing at least 10% of baseline weight was 6% for hydrochlorothiazide, 8% for
      spironolactone, 68% for dextroamphetamine sulfate, and 4% for captopril. The
      percentage losing >20% and >30% of baseline weight in the same treatment groups
      was 28% and 10% for dextroamphetamine therapy but 0% for the other three groups.
      Of the women who failed to lose weight with one of the nonamphetamine therapies
      during the first 6 months, 132 were then treated with dextroamphetamine; 68% lost
      =10% of their baseline weight, and 30% and 7% of patients lost =20% and =30%,
      respectively. With use of the classic definition of idiopathic orthostatic edema
      (urinary output of <55% of ingested water load in 4 hours), only 58 of the 200
      study patients had this diagnosis; however, 144 patients excreted <75% of the
      load. Comparison of the efficacy of amphetamine therapy in patients with <75%
      versus =75% urinary excretion showed 120 of 131 (92%) lost =10% in the former
      category versus only 4 of 51 (8%) in the latter. Of the 58 patients who excreted
      <55% of the water load, 52 (90%) lost =10% of baseline weight with amphetamine
      therapy. The patients noted no effects of therapy on dietary consumption. The
      responsiveness of the patients to amphetamine therapy during the second 6-month
      period despite failing to lose weight with the three other therapies suggests
      that no inadvertent bias was present in the randomization process. Thus, the
      results suggest that some women who are recalcitrant to dietary weight loss may
      have a mild type of water retention that is refractory to diuretics but
      responsive to amphetamines.

PMID- 15251578
TI  - Factitious Cushing's syndrome: discovery with use of a sensitive
      immunoradiometric assay for corticotropin.
AB  - Factitious Cushing's syndrome is an unusual problem that may be clinically and
      biochemically indistinguishable from endogenous hypercortisolism. Results of
      biochemical studies may be misleading because of cross-reactivity of synthetic
      corticosteroids or their metabolites with plasma or urine cortisol. Because of
      its lack of specificity, radioimmunoassay (RIA) for corticotropin
      (adrenocorticotropic hormone or ACTH) may not show completely suppressed results
      in patients with surreptitious use of glucocorticoids. A new sensitive and
      specific immunoradiometric assay (IRMA) for ACTH demonstrates reliably suppressed
      levels after administration of glucocorticoids. In this report, we describe a 37
      year-old woman with typical clinical and biochemical features of ACTH-dependent
      hypercortisolism. Metabolic evaluation had shown urinary free cortisol excretion
      of 7,499 nmol/day and plasma ACTH-RIA levels of 13.2 and 33.0 pmol/L on two
      separate occasions. The use of IRMA for the measurement of ACTH during inferior
      petrosal sinus sampling revealed a very low peripheral ACTH concentration (=0.4
      pmol/L) and a considerably blunted response to ovine corticotropin-releasing
      hormone, findings that suggested ACTH-independent Cushing's syndrome. Plasma
      samples obtained during inferior petrosal sinus sampling were assayed for
      prednisolone and showed a concentration of 360 nmol/L; thus, the presence of
      factitious Cushing's syndrome was confirmed. Some commercial ACTH-RIA
      measurements may be unreliable in distinguishing ACTH-dependent from ACTH
      independent hypercortisolism. ACTH-IRMA levels are low in patients with ACTH
      independent Cushing's syndrome and will be helpful in identifying factitious
      Cushing's syndrome.

PMID- 15251579
TI  - Steroid cell tumor associated with primary amenorrhea and virilization.
AB  - A 22-year-old woman sought medical advice because of primary amenorrhea and
      virilization that was manifested by facial hirsutism, temporal balding, and
      clitorimegaly. Plasma steroid levels were determined at the time of initial
      assessment; androstenedione and testosterone were increased in comparison with
      normal values. Vaginal ultrasonography revealed the presence of a mass localized
      to the right ovary. The patient underwent oophorectomy, and pathologic
      examination of the surgical specimen led to the identification of a steroid cell
      tumor associated with a polycystic ovary. Tumor steroid-metabolizing enzymes were
      evaluated in vitro: 17alpha-hydroxylase, 3beta-hydroxysteroid dehydrogenase/
      delta5-->4-isomerase, 17beta-hydroxysteroid oxidoreductase, and 5a-reductase,
      which are required for androgen synthesis, were present in the tumor tissue.
      Postoperatively, plasma androstenedione and testosterone levels returned to
      normal. This study demonstrated that the tumor was the source of the increased
      levels of androgen precursor and androgen in this woman; excess tumor-derived
      androgen may have been the trigger in the development of the polycystic ovary.

PMID- 15251580
TI  - Repetitive responses to clomiphene citrate in normal women of late reproductive
      age.
AB  - The hormonal response to clomiphene citrate (CC) has been used to evaluate
      ovarian reserve. In the current study, we tested the reproducibility of response
      to 100 mg of CC administered for 5 days in a group of 20 women, 35 to 40 years of
      age, with regular menstrual cycles who completed 57 cycles during the study.
      Individual hormonal responses to repeated stimulation were not identical. When
      ovarian responsiveness to CC was categorized as "low" (E(2) and E(2)/FSH ratios
      =200 pg/mL and =20, respectively) or "high" (E(2) =400 pg/mL and E(2 /FSH ) =61),
      however, responses of individual subjects seldom spanned both categories.
      Specifically, only 3 of 20 subjects had both low and high E(2) and low and high
      E(2/FSH ) ratios (P<0.001). In addition, seven subjects were identified as FSH
      hyperresponsive in at least one cycle (post-CC FSH =10 IU/L). Only 2 of 21 cycles
      in these seven subjects had post-CC E(2)/FSH ratios =61, in comparison with 20 of
      36 cycles in the other 13 subjects (P<0.01). Thus, despite the cycle-to-cycle
      variations, the hormonal response of an individual subject could usually be
      categorized as occurring at one or the other end of the spectrum of ovarian
      function, these two extremes probably signifying good and poor ovarian reserve.
      This prediction is further strengthened by the observation of a significant
      negative correlation between the FSH and E(2) responses after administration of
      CC (P=0.05).

PMID- 15251581
TI  - Role of behavioral therapy in the management of obesity.
AB  - Behavioral therapy for obesity that is, the application of learning theory to
      obesity treatment is now a standard component of weight-loss programs. The
      hallmark of behavioral therapy for obesity is self-monitoring of eating behavior,
      but techniques of stimulus control, self-reward, cognitive restructuring,
      nutrition education, and physical activity are also emphasized. Although
      behavioral treatment programs that incorporate lengthier and more intensive
      regimens are often successful in producing short-term weight loss, most patients
      have regained much or all of their lost weight at long-term follow-up. One
      approach to this problem has been to supplement behavioral treatment with other
      modalities such as very-low-calorie diets, surgical procedures, and medication.
      Whatever the initial treatment, obesity clearly must be approached as a chronic
      disorder that necessitates long-term intervention, and relapse prevention and
      weight maintenance strategies are crucial for long-term success. Another
      important development in behavioral treatment of obesity has been the attempt to
      identify subgroups of obese persons, such as those with uncontrolled binge
      eating, who might benefit from specific management approaches. Treatment programs
      for binge eating are strongly influenced by techniques developed for other types
      of eating disorders such as bulimia. Although use of only behavioral therapy is
      insufficient, it has an important adjunctive role for many patients particularly
      as we improve our abilities to tailor treatment to the individual subject and to
      promote long-term weight maintenance.

PMID- 15251582
TI  - Weight cycling: more questions than answers.
AB  - Most men and women who attempt to lose weight will regain any weight that is
      lost. This cycle of weight loss and regain - referred to as weight cycling is a
      recurrent phenomenon for many patients. With the increased frequency of obesity
      and the increased prescriptions for weight-loss practices without an associated
      increase in the success of weight-loss maintenance, the concerns about weight
      cycling have grown. Recent literature has focused on the possible physiologic and
      psychologic hazards of weight cycling. Review of both human and animal studies
      indicates no conclusive evidence about harmful effects of weight cycling. Most
      studies show no adverse effects on metabolism. Some observational studies
      indicate an association between variations in body weight and increased morbidity
      and mortality but do not distinguish between voluntary and involuntary weight
      loss events. The studies of psychologic hazards have been limited, and little
      convincing information is available. Without more compelling evidence of the
      risks of weight cycling, warnings overriding safe, effective weight-loss
      treatments for the obese are unwarranted. Appropriately designed studies are
      urgently needed to assess the long-term efficacy of procedures and treatments
      that promote weight-loss maintenance and to provide further analyses of the
      effects of weight cycling.

PMID- 15251583
TI  - Obesity treatment: examining the premises.
AB  - Five basic premises underlie the recommendation that obese persons should lose
      weight: (1) obesity is physically unhealthy; (2) in obese persons, weight loss
      improves physical health; (3) long-term weight loss is possible; (4) the benefits
      of weight loss exceed the costs; and (5) weight loss is superior to or can add
      incrementally to the effects of alternative methods of improving the health and
      happiness of obese persons. Although the data are occasionally ambiguous, they
      generally support these premises. Obesity apparently causes increased morbidity
      and decreased longevity, even after controlling for many plausible confounding
      factors. Clinical studies consistently show that weight loss reduces morbidity.
      No adequate data exist on which to evaluate the effects of weight loss on
      mortality among obese persons. Additional data are needed, but long-term weight
      loss seems possible, although such losses remain difficult to maintain. A crude
      estimate is that about 20% of obese persons who attempt to lose weight can
      achieve and maintain a clinically meaningful weight loss. The short-term health
      and psychologic costs of gradual weight loss are minor, manageable, and easily
      surpassed by the short-term health and psychologic benefits. Long-term effects of
      weight loss on mortality are difficult to judge, and further research is needed.
      Weight loss can add incrementally to the effects of alternative methods to
      improve health and happiness among obese persons. Thus, these "alternatives" are
      better termed "complementary approaches," and their use need not preclude
      attempts at weight loss. Finally, we provide several guidelines to help
      practitioners assist obese persons in making reasonable informed decisions about
      weight loss.

PMID- 15251584
TI  - Thyroglobulin: a clinical review.
AB  - The introduction of the new assays for thyroglobulin (Tg) with a sensitivity of 1
      to 3 mg/L has made it unnecessary to terminate thyroxine suppression therapy to
      determine Tg level. Thyroid-stimulating hormone should always be assessed in
      conjunction with the Tg to ensure that it is not high; as long as it is
      suppressed to normal, subnormal suppression is unnecessary. A total thyroidectomy
      is not a prerequisite for using Tg as a tumor marker; the Tg is equally reliable
      in those patients who have undergone a near-total or a subtotal thyroidectomy.
      Even patients who have undergone only a lobectomy may benefit from Tg monitoring
      if the level is low; however, an initial high Tg level (without a previous low Tg
      value) should not be interpreted as suggestive of cancer. Postoperative 131 I
      ablation is not necessary for an accurate Tg measurement. The finding of anti-Tg
      antibodies in patients with thyroid cancer remains a major problem, but other
      technical problems related to the absence of an international Tg standard have
      now been eliminated. Monitoring the Tg level reliably detects early recurrent
      disease in patients who have undergone a surgical procedure for thyroid carcinoma
      and are receiving thyroxine suppression therapy. Only those patients with Tg
      levels that exceed 3 to 5 mg/L or with clinical evidence of recurrence need to
      discontinue thyroxine treatment and have a 131 I scan. This approach can
      substantially decrease the expense, inconvenience, and morbidity of performing
      routine scans on these patients.

PMID- 15251585
TI  - Recurrent hyperthyroidism after radioiodine-induced hypothyroidism: report of two
      cases and literature review.
AB  - The practice at the Mayo Clinic in treating Graves' disease with radioiodine (131
      I) is to achieve a hypothyroid state. Less than 10% of the patients need more
      than one dose. Although cases of transient hypothyroidism have been reported
      after treatment with 131 I, the recurrence of hyperthyroidism is unusual after
      hypothyroidism has been induced with 131 I. We studied two cases seen at our
      institution in the past year in which the circumstances behind the recurrence
      have never been reported previously. The first case illustrates a recurrence of
      hyperthyroidism after the patient had received 38.5 mCi of 131 I. The second
      patient had recurrence of hyperthyroidism after 22 years of replacement therapy
      with levothyroxine. Both patients had increased levels of thyroid-stimulating
      immunoglobulin. We believe that the recurrence of the hyperthyroid state in these
      two patients was due to incomplete ablation of the thyroid. Apparently 131 I
      caused hypothyroidism, but residual cells remained viable and under continuous
      stimulation of thyroid-stimulating immunoglobulin produced recurrent
      thyrotoxicosis.

PMID- 15251586
TI  - Meningioma in congenital adrenal hyperplasia.
AB  - A diversity of malignancies have been reported in patients with congenital
      adrenal hyperplasia. We report a case of multiple meningiomas, tumors which are
      more common in females and reported to have sex steroid receptors, in a 46,XX
      male (severe female hermaphrodite raised as a male) with 21-hydroxylase
      deficiency. The patient has been treated with glucocorticoids since 3 years of
      age and testosterone since puberty.

PMID- 15251587
TI  - Life-threatening hyponatremia due to the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) in a patient with the miller fisher syndrome.
AB  - We report a life-threatening hyponatremia due to SIADH which developed suddenly
      in a patient with the Miller Fisher syndrome (a variant of Guillian Barre
      syndrome characterized by complete ophthalmoplegia, ataxia, and areflexia). A 55
      year-old female was admitted with a clinical picture of the Miller Fisher
      syndrome. Cerebrospinal fluid was acellular with elevated proteins, and
      electromyographic changes were characteristic of polyneuropathy. On the third day
      of admission the patient was found to be mentally confused with a serum sodium of
      108 mmol/L. Serum osmolality was 236 mosm/L and urine osmolality was 636 mosm/L.
      Urine sodium was 103 mmol/L. The serum sodium normalized after treatment with a
      single dose of intravenous furosemide, hypertonic saline infusion and fluid
      restriction. To our knowledge, this is the first description of SIADH developing
      in a patient with the Miller Fisher syndrome.

PMID- 15251588
TI  - Humoral hypercalcemia of hepatocellular carcinoma associated with elevated levels
      of parathyroid-hormone-related-peptide.
AB  - Parathyroid-hormone-related-peptide (PTHrP) has been shown to be important in the
      pathogenesis of hypercalcemia of malignancy. The malignancies most commonly
      associated with hypersecretion of PTHrP include squamous cell carcinoma and
      breast cancer. The pathogenesis of hypercalcemia associated with hepatocellular
      carcinoma was evaluated in this study. Two male patients with hepatocellular
      carcinoma were found to have severe hypercalcemia at initial presentation. PTHrP
      was measured with radioimmunoassay in these two patients before treatment as well
      as in nine other patients with hepatocellular carcinoma but without
      hypercalcemia. The levels were markedly elevated in the two patients with
      hypercalcemia (29.3 and 32.1 pM), but were less than 5 pM in the nine patients
      without hypercalcemia. These results suggest that PTHrP was important in the
      pathogenesis of hypercalcemia associated with hepatocellular carcinoma in these
      men.

PMID- 15251589
TI  - PTHrP-mediated hypercalcemia in a calcitonin-producing islet cell tumor.
AB  - Calcitonin is a peptide hormone that may decrease serum calcium levels. This case
      report describes a patient with a calcitonin-producing islet cell tumor who was
      also hypercalcemic. Parathyroid hormone-related peptide (PTHrP) levels were
      elevated. No other cause for hypercalcemia was found. The hypercalcemia resolved
      when the tumor was treated with chemotherapy. PTHrP levels also decreased with
      the chemotherapeutic treatment. This is the first report of a patient with a
      calcitonin-producing islet cell tumor and hypercalcemia mediated by PTHrP.

PMID- 15251590
TI  - Assessment and management of the patient with Graves' ophthalmopathy.
AB  - The appropriate management of a patient with Graves' ophthalmopathy (GO) can be
      determined only following a careful assessment of the signs and symptoms of the
      disease. A detailed examination and discussion allows the clinician to determine
      which components of the disease are most troublesome to that particular patient.
      The advantages and disadvantages of the various treatment options for each
      disease component can be best understood in light of current concepts of the
      pathogenesis of GO. This paper will begin with a discussion of the histologic and
      gross pathologic features of the disease, followed by a brief review of
      pathogenic mechanisms responsible for their development. The assessment of a
      patient with GO will be discussed and the modes of therapy available to address
      each of the signs and symptoms will be reviewed. Readers interested in a more
      detailed discussion of the management of GO are encouraged to read the excellent
      recent review by Drs. Burch and Wartofsky.

PMID- 15251591
TI  - From motilin to motilides: a new direction in gastrointestinal endocrinology.
AB  - Investigation into gastrointestinal irritation from the use of erythromycin lead
      to the discovery of the gastrointestinal motor effect of this antibiotic.
      Erythromycin and gastrointestinal peptide motilin share many similar
      gastrokinetic activities, and studies indicate that erythromycin mimics the
      effect of motilin through motilin receptor agonism. Since erythromycin is readily
      available for clinical use, it may offer an alternative therapeutic approach to
      gastroparesis and related conditions. Several analogs of erythromycin without
      antimicrobial activity are also shown to possess similar motor effects, thus
      termed "motilides". A growing number of motilides may expand our knowledge on
      gastrointestinal peptides.

PMID- 15251592
TI  - Graves' disease and pregnancy.

PMID- 15251593
TI  - The medical management of Graves' disease.
AB  - There are many different approaches to treat Graves' hyperthyroidism. Medical
      therapy is used short-term to prepare patients for radioiodine or surgery, or it
      is used long term with the hope of achieving a remission. b-adrenergic blocking
      agents are useful in all patients without a contraindication, especially
      selective long-acting agents such as atenalol. Thionamides are the mainstay of
      medical treatment. Methimazole is more potent, may be used as a single daily
      dose, and may have less toxicity than PTU. Severe hyperthyroidism or thyroid
      storm may be treated with methimazole and ipodate. Patients are prepared for
      surgery with methimazole and SSKI, or b-adrenergic blocking agents and ipodate.

PMID- 15251594
TI  - The role of iodine in the management of Graves' disease.

PMID- 15251596
TI  - Classification of diabetes: is it time for 1.5?

PMID- 15251595
TI  - A clinical guide to the management of Graves' disease with radioactive iodine.
AB  - More than 50 years have passed since radioactive iodine (RAI) was initially
      demonstrated as a therapeutic modality for the treatment of Graves' Disease.
      Today, more than a million patients have been treated with RAI. RAI is considered
      safe and highly effective. Its side-effect profile, ease of administration, and
      relative cost make RAI the treatment of choice for Graves' Disease of
      thyroidologists in this country. Questions continue to be raised as to which
      patients will benefit most from RAI therapy. Marked differences still exist
      between the practice preferences of thyroidologists as to whom, when, and how to
      treat with RAI. Factors that influence patient selection for RAI include age, the
      presence of pre-existing ophthalmopathy, lifestyle, history of previous treatment
      failure, and goiter size. Treatment goals, dosimetry, use of thionamides prior to
      therapy, safety recommendations following therapy, and prophylactic therapy with
      glucocorticoids for patients with ophthalmopathy highlight are some of the
      controversial issues facing the endocrinologist treating Graves' Disease with
      RAI. This symposium article reviews the current management of Graves' Disease
      with RAI.

PMID- 15251597
TI  - A pilot study of urine iodine excretion in a selected cohort in phoenix.
AB  - A pilot study of twenty-four hour urine iodine excretion was carried out in 34
      adults who were employees (or their spouses) of Maricopa Medical Center and
      residents of the Phoenix area. Based on previous estimations, our expectation was
      that urine iodine excretion values should be high. The mean value was 219 +/- 25
      microg/day in the first collection and 229 +/- 23 microg/day when the collection
      was repeated 4 months later. The results support an adequate amount of iodine in
      the diet for the group. However, they indicate an iodine intake lower than what
      previously published studies had estimated for this area. It is not clear whether
      these results reflect a regional or national trend of decreased dietary iodine
      intake or changes in dietary iodine intake limited to the cohort studied. These
      data indicate a need for further study to clarify this finding in view of
      possible clinical implications resulting from changes in iodine intake.

PMID- 15251598
TI  - Acth-independent Cushing's syndrome: bilateral cortisol-producing adrenal
      adenomas.
AB  - ACTH-independent Cushing's syndrome (CS) usually results from a solitary
      adrenocortical adenoma. We recently encountered a patient with ACTH-independent
      CS associated with bilateral adrenal enlargement. The evaluation led us to
      consider some rare but interesting entities. The patient was a 69 year-old woman
      who had a 10-15 year history of controlled hypertension, back pain associated
      with osteoporosis, easy bruising, and truncal obesity. Her medications included
      conjugated estrogens. Physical examination revealed classical features of CS. She
      had a raised blue lesion on her buccal mucosa. Plasma cortisol concentrations
      were elevated at 36 (a.m.) and 38 (p.m.) microg/dL. Urinary free cortisol was
      normal at baseline (65 microg/24 hours) but failed to suppress adequately in
      response to the low-dose dexamethasone suppression test (75 microg/24 hours). The
      plasma ACTH concentration was undetectable. Plasma cortisol concentrations failed
      to suppress (37 microg/dL) with an 8 mg overnight dexamethasone test. A CT scan
      of the abdomen revealed bilateral adrenal masses. The possibilities of food
      induced CS and primary pigmented nodular adrenal disease were excluded by a lack
      of marked stimulation in cortisol secretion to a mixed-meal and dermatologic
      confirmation of the buccal mucosa lesion as an angioma and not a blue nevus.
      Adrenal venous sampling showed cortisol secretion from both adrenals. The patient
      underwent bilateral adrenalectomy with pathology confirming bilateral adenomas.
      This case illustrates an unusual application of selective venous sampling in the
      CS evaluation and raises questions about the pathogenesis of cortisol-secreting
      adrenocortical adenomas.

PMID- 15251599
TI  - A carotid body and glomus jugulare paraganglioma secreting norepinephrine.
AB  - Extra-adrenal paragangliomas (PGOMAs) are rare and can occur anywhere along the
      sympathetic chain including the carotid body, glomus jugulare, vagal bodies,
      ganglium tympanicum, larynx, ciliary bodies, organs of Zuckerkandl, urinary
      bladder, and other locations. These are microscopically identical. The
      embryological origin is from neural crest cells. One to three percent are
      reported to be functioning, predominantly secreting norepinephrine. Diagnosis of
      a functioning PGOMA can be delayed, even when symptoms of catecholamine
      hypersecretion are present. Furthermore, diagnostic testing and surgery have a
      significant morbidity if the diagnosis is not considered in advance, as
      illustrated by the following cases. PGOMAs can be sporadic or familial with an
      autosomal dominant pattern with variable penetrance. They can be multicentric and
      associated with other endocrine gland tumors. Benign and malignant PGOMAs have
      been described, with malignancy being defined by lymph node metastasis. Few cases
      of functioning glomus jugulare and carotid body tumors have been reported in the
      medical literature.

PMID- 15251600
TI  - Kallmann's syndrome with diabetes insipidus.
AB  - A case is presented of a male with Kallmann's syndrome who at the age of 27
      developed central diabetes insipidus. Previously, Kallmann's syndrome has been
      found to be associated with an altered osmotic threshold for vasopressin release
      and impaired thirst sensation, but to our knowledge, this is the first reported
      association with diabetes insipidus.

PMID- 15251601
TI  - Case report: increased levothyroxine requirement in a patient with cryptic celiac
      sprue disease.
AB  - An increased requirement for levothyroxine may be due to poor patient compliance,
      pregnancy, low potency levothyroxine preparations, interfering drugs and small
      intestinal disease. Data on thyroid hormone absorption in celiac sprue disease is
      limited to a single study involving four patients without thyroid disease, in
      which malabsorption of a single dose of radiolabeled levothyroxine was noted in
      three of the four subjects. Increased levothyroxine requirements have not been
      reported in hypothyroid patients with celiac sprue. Furthermore, cryptic celiac
      sprue has never been described to cause levothyroxine malabsorption. We report
      such a patient in whom cryptic celiac sprue was an important cause of
      levothyroxine malabsorption with increased thyroid hormone requirement.

PMID- 15251602
TI  - Endocrine hypertension.
AB  - All hypertension, in one sense, is endocrine in origin. For the 5% of
      hypertension that is secondary to a specific mechanism, the majority can be
      attributed to an endocrinopathy, either too much (Cushing's syndrome, primary
      aldosteronism, renovascular disease, pheochromocytoma) or too little (renal
      parenchymal disease). For the 95% of hypertension that remains idiopathic or
      primary, the multiple environmental factors that act upon a genetic
      predisposition almost all mediate their effects through hormonal pathways (Figure
      1). Since endocrinologists are more likely to deal with the 5% of hypertension
      that is secondary (Table 1), this review will cover their diagnosis and
      management in greater detail than the 95% categorized as primary hypertension.

PMID- 15251603
TI  - Iodine: maintenance of optimal intake.

PMID- 15251605
TI  - Questions & some answers on Graves' eye disease.

PMID- 15251604
TI  - The pathogenesis of Graves' disease.
AB  - We have hypothesized over many years that Graves' disease (GD) and the other
      autoimmune thyroid diseases (AITD) are each due to antigen-specific defects in
      suppressor (regulatory) T lymphocyte function. There have been several reports
      dealing with the role of regulatory T lymphocyte subsets, ie., that will prevent
      autoimmune disease in these and other organ-specific autoimmune diseases. In
      AITD, suppressor T cells have been shown to be less well activated by relevant
      antigen, but are normally activated by irrelevant antigen; suppressor T cells
      from normal persons react equally well to both. In GD, these cells have been
      shown to be inadequately activated by TSH receptor antigen, but are normally
      activated by irrelevant autoantigen. This reduction is partial only, and
      insufficient itself to precipitate the autoimmune disease; further insults from
      the environment are necessary to further reduce generalized regulatory cell
      activity, adding to the genetically induced specific regulatory cell dysfunction,
      which appears in turn to be due to a specific defect in the presentation of a
      specific antigen. This, in turn, may relate to abnormalities of the genes
      responsible for antigen presentation. The end result is activation of appropriate
      helper and effector T cells, the stimulation by these of appropriate B
      lymphocytes, and the concurrent production of cytokines. These events lead to
      functional changes within the target cell which itself will express Class II
      antigens, heat shock proteins, and intercellular adhesion molecules, all of which
      amplify the immune response. Moreover, the activation of helper T lymphocytes by
      specific antigen depends on the availability of normal amounts of antigen being
      presented to them by antigen-presenting cells. Thus, there is no need to invoke
      any primary abnormality or infection of the thyroid cell, or any cross-reacting
      antigen of microorganismic origin to initiate this process. What is required is
      an abnormality of antigen-presentation such that regulatory cells are not
      properly activated, plus some additive environmental disturbance acting on the
      immune system. GD specifically results from the production by B lymphocytes of an
      antibody directed against the TSH receptor which stimulates the thyrocyte in a
      manner similar to TSH, but for a much longer interval. There are also antibodies
      to the thyrotrophin (TSH) receptor which block the action of TSH. Thyroid
      stimulating antibody is typical of GD and is detectable in about 95% of cases,
      but is also seen in destructive thyroiditis transiently. It tends to decline with
      antithyoid drug therapy, and rises further (for several months) after 131 I
      treatment. It may slowly decline after subtotal thyroidectomy. It also declines
      in the third trimester of pregnancy but sometimes is sufficiently high to cause
      foetal and neonatal passive transfer GD. It tends to rebound in the mother after
      delivery and may result in postpartum GD. The blocking antibody may cause
      atrophic thyroiditis and hypothyroidism. Antimicrosomal antibody has now been
      shown to be antithyroperoxidase. It correlates moderately well with thyroid
      dysfunction in Hashimoto's thyroiditis (HT) and GD, while antithyroglobulin is of
      much less value. Graves' ophthalmopathy is still not well understood, and its
      precise relationship to Graves' hyperthyroidism has yet to be worked out. However
      the retroorbital fibroblast is now emerging as the most likely target cell, with
      retroorbital muscle involvement possibly secondary. A recent observation of a
      genomic point mutation on the TSH receptor on fibroblasts from patients with
      Graves' ophthalmopathy but not normal persons raises interesting possibilities.

PMID- 15251606
TI  - Elevated calcium level in parathyroid cyst fluid.
AB  - Parathyroid cysts are uncommon neck masses. The diagnosis is generally
      established when the parathormone level is found to be elevated in the typically
      clear cyst fluid obtained by fine needle aspiration. We present a case where the
      serum and cyst fluid intact parathormone levels were normal yet the diagnosis was
      established by demonstrating an elevated fluid calcium level. The cyst recurred
      after two attempts at aspiration, so the patient underwent a curative operative
      excision.

PMID- 15251607
TI  - Familial dysalbuminemic hyperthyroxinemia: cumulative experience in 29
      consecutive patients.
AB  - PURPOSE: The syndrome of familial dysalbuminemic hyperthyroxinemia (FDH), an
      inherited abnormality characterized by the presence of a variant serum albumin
      with preferential affinity for T4, is recognized with increasing frequency as a
      cause of elevated total and free T4 serum values in clinically euthyroid patients
      with normal TSH levels. Hyperthyroxinemia caused by this syndrome is occasionally
      confused with hyperthyroidism or thyroid hormone resistance syndromes, which may
      prompt unnecessary treatment. To better define the clinical and biochemical
      characteristics of patients with FDH, we undertook a retrospective analysis of
      the experience at our institution with this condition. PATIENTS: We reviewed our
      cumulative experience in 29 consecutive patients with FDH diagnosed between 1970
      and 1991. RESULTS: FDH was diagnosed in 18 males and 11 females (mean age, 42.7
      years) on the basis of clinical euthyroidism, increased total T4 and
      increased/normal free T4 serum values, normal T3 and TSH serum values, increased
      T4 binding to serum albumin, and low/normal T4 binding to T4-binding globulin and
      serum prealbumin. Clinical thyroid examination revealed no abnormalities except
      for goitre in five patients, and the results of radioiodine uptake studies were
      normal. Patients with subsequently documented FDH were referred for evaluation of
      "unusual" findings on thyroid function tests or FDH was detected on routine
      thyroid function tests or identified on family screening. Euthyroid
      hyperthyroxinemia in combination with a family history compatible with FDH
      correctly suggested FDH in seven patients. CONCLUSIONS: Clinical euthyroidism in
      conjunction with a normal basal sensitive TSH value in a hyperthyroxinemic
      patient differentiates euthyroid hyperthyroxinemia from thyrotoxicosis, obviating
      unnecessary therapy. Detection of excessive thyroxine binding to serum albumin
      establishes the diagnosis of FDH and allows it to be differentiated from thyroid
      hormone resistance syndromes. After a diagnosis of FDH has been established,
      family screening is advisable. Hyperthyroxinemia in clinically euthyroid patients
      ("euthyroid hyperthyroxinemia") is recognized with increasing frequency and
      should prompt a careful diagnostic evaluation. The differential diagnosis of this
      condition may be difficult because it includes various common and unusual
      syndromes, including quantitative or qualitative changes in thyroid hormone
      binding proteins, circulating antibodies against thyroid hormones, resistance to
      thyroid hormones, influences from drugs, and acute somatic or psychiatric illness
      (1). The recently recognized syndrome of familial dysalbuminemic
      hyperthyroxinemia (FDH), an inherited abnormality with autosomal dominant
      transmission, is characterized by the presence of a variant serum albumin with
      preferential affinity for T4 (2-4). Typically, FDH is detected incidentally or
      patients are referred to endocrinologists on the basis of "unusual" results on
      routine thyroid function testing, revealing consistently elevated total T4 and
      elevated or normal free T4 values in a clinically euthyroid patient with normal
      TSH levels (1,5). Unfortunately, hyperthyroxinemia due to FDH may be confused
      with hyperthyroidism or thyroid hormone resistance syndromes, prompting repeated
      unnecessary laboratory testing and possibly even inappropriate treatment
      (1,3,6,7). Herein, we describe the clinical and biochemical characteristics of 29
      consecutive patients with documented FDH.

PMID- 15251608
TI  - Fine-needle aspiration biopsy: use in diagnosis and management of pediatric
      thyroid diseases.
AB  - Fine-needle aspiration (FNA) biopsy of the thyroid is a reliable, safe, cost
      effective, and widely used test. Its introduction and application have had a
      significant impact in the management of nodular thyroid diseases in adults.
      However, its utility in pediatric practice is not recognized or emphasized.
      During the last 12 years we performed 10,971 FNAs; 57 (0.5%) were in patients
      younger than age 17 years. Among 47 of these biopsies, 66% were benign, 15% were
      malignant, 6% were suspicious for malignancy and 13% were nondiagnostic. Biopsy
      was most often (96%) performed for the evaluation of diffuse or nodular goiter.
      The most common benign cytologic diagnosis was colloid goiter in 17 of 31
      patients (55%) and Hashimoto's thyroiditis in 9 of 31 patients (29%). There were
      no false-positive results and there was one false-negative cytologic result.
      Among patients who had malignancy proved histologically, nine patients (75%) had
      papillary thyroid cancer. In this study, FNA biopsy was crucial in deferring
      surgery in 28 of 47 patients (60%). It is clear that the application of FNA
      biopsy prevents unnecessary surgery and improves surgical selection of patients
      with thyroid malignancy. On the basis of our extensive experience, we recommend
      FNA biopsy as the first diagnostic test for pediatric patients with nodular
      thyroid lesions.

PMID- 15251609
TI  - Autoimmune Addison's disease after treatment with interleukin-2 and tumor
      infiltrating lymphocytes.
AB  - Autoimmune thyroiditis with hypothyroidism is a well-known complication of
      immunotherapy with interleukin-2 (IL-2) with or without lymphokine-activated
      killer (LAK) cells. To date, however, no cases of IL-2/LAK-induced autoimmune
      adrenalitis with adrenal insufficiency have been reported. We describe a patient
      who developed primary adrenal insufficiency following IL-2/tumor-infiltrating
      lymphocytes (TIL) immunotherapy for renal cell carcinoma. A 64-year-old male with
      renal cell carcinoma metastatic to bone, skin, lung, and the central nervous
      system presented for IL-2/TIL treatment. Nine months earlier, he had undergone a
      right nephrectomy and adrenalectomy. He had already received two courses of IL-2
      and one course of IL-4 following surgery. Dynamic studies of adrenal function
      performed prior to IL-2/TIL immunotherapy demonstrated intact cortisol and
      aldosterone responses to ACTH as well as negative adrenal antibodies. One week
      after IL-2/TIL therapy, the patient developed a nonanion gap metabolic acidosis,
      hypotension and hypoglycemia. Adrenocortical function was re-evaluated
      demonstrating blunted cortisol and aldosterone responses to ACTH with an elevated
      plasma ACTH confirming the presence of primary adrenal insufficiency. Adrenal
      antibodies were now positive. Hydrocortisone and fludrocortisone were given with
      a good clinical response. We suggest immunotherapy with IL-2/TIL may cause
      adrenal insufficiency by activating autoimmune adrenalitis.

PMID- 15251610
TI  - Estrogen replacement therapy in osteoporosis: advances and controversies.

PMID- 15251611
TI  - Calcitonin in the prevention and therapy of osteoporotic syndromes.
AB  - It is now generally accepted that estrogen status, exercise and adequate calcium
      intake are the singularly most important factors which guarantee the assumption
      of genetically programmed peak bone mass. Physicians also recognize that estrogen
      replacement therapy is not only essential to prevent bone loss in the early
      postmenopausal female, but also for the long-term preservation of bone mineral
      density. The efficacy of either continuous or intermittent calmon calcitonin
      administration in preventing further bone loss and in some instances decreasing
      fracture incidences in established osteoporotic syndromes is currently well
      established. As noted during a variety of controlled investigations performed
      both in the United States and abroad, and in the Physician's Resource Manual on
      Osteoporosis published by the United States National Osteoporosis Foundation,
      salmon calcitonin is also effective in early postmenopausal women who are not
      candidates for estrogen replacement therapy in addition to those patients with
      established osteoporosis. The practicing physician should acknowledge that of all
      the anti-resorptive agents recommended for therapy in osteoporotic syndromes,
      estrogens and salmon calcitonin are currently the only two drugs recommended by
      the U.S. Food and Drug Administration (USFDA) as safe and effective as treatment
      modalities in osteoporosis.

PMID- 15251612
TI  - Growth hormone, skeletal growth factors and osteoporosis.
AB  - Bone remodeling is regulated by systemic hormones and growth factors acting in
      concert to maintain normal bone mass. Growth hormone has important effects on
      bone metabolism and acts by stimulating the production of insulin-like growth
      factor (IGF) I in the liver. Conditions of growth hormone deficiency have
      decreased bone mass that could be modified by growth hormone administration.
      Skeletal cells synthesize a variety of growth factors with diverse properties and
      levels of regulation. IGF I and II seem to play a major role in the local
      regulation of bone remodeling, and other growth factors have important mitogenic
      properties. Skeletal growth factors may be regulated at the level of synthesis,
      activation, receptor binding or binding proteins. Growth factors such as IGF I
      could be considered for the systemic treatment of various bone disorders, or
      drugs could be developed to modify the synthesis or activity of the locally
      produced factors. Additional research should result in the development of novel
      approaches to the treatment of osteoporosis.

PMID- 15251613
TI  - Role of vitamin D in the pathogenesis and treatment of osteoporosis.
AB  - Alterations in vitamin D metabolism normally occur after the menopause and with
      aging. Increases in skeletal remodeling as a consequence of estrogen deficiency
      lead to increased bone resorption, suppression of serum 1,25-dihydroxy-vitamin D
      and intestinal absorption of calcium and increases in urinary calcium. Age
      related changes in vitamin D metabolism include diminished dermal production of 7
      dehydrocholesterol, the precursor of previtamin D(3), vitamin D deficiency as a
      consequence of inadequate intake or exposure to sunshine (individuals may be
      institutionalized or housebound), a decline in intestinal vitamin D receptors and
      diminished intestinal absorption of calcium and secondary hyperparathyroidism
      which leads to further bone loss. These changes also have been implicated in the
      pathogenesis of senile osteoporosis. Treatment with vitamin D and its analogues
      such as 1,25-dihydrox-yvitamin D(3 )is sometimes of value in preventing bone loss
      and fractures in patients with postmenopausal osteoporosis and senile
      osteoporosis. However, the drugs have not been approved for treatment and
      prevention of osteoporosis.

PMID- 15251615
TI  - RET germline mutation in codon 791 in a family representing 3 generations from
      age 5 to age 70 years: should thyroidectomy be performed?
AB  - OBJECTIVE: To describe a kindred with a rare RET germline mutation in codon 791
      and discuss potential management strategies. METHODS: We present clinical and
      biochemical data as well as results of mutation analysis in our study subjects
      and provide an overview of related published reports. RESULTS: Multiple endocrine
      neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the
      development of medullary thyroid carcinoma (MTC), pheochromocytoma, and
      parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for
      this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be
      caused by RET mutations in codon 791. Deaths from gene carriers with mutations in
      these codons have not yet been reported. In general, gene carriers with these RET
      mutations have late-onset MTC. Because only a few kindreds with this specific
      mutation have been identified and no long-term follow-up data are available,
      management of these patients can be a challenge. We illustrate the difficulties
      with decisions about not only when to perform thyroidectomy in these patients but
      also whether thyroidectomy should even be considered in such gene carriers with a
      benign course. Our reported kindred included four carriers with a codon 791 RET
      germline mutation, one of whom had the rare concomitant occurrence of acromegaly
      and MEN 2A. The 70-year-old mother had acromegaly and hyperparathyroidism but
      normal serum calcitonin levels and normal findings on thyroid ultrasound
      examination. She refused pentagastrin testing and any surgical intervention. The
      37-year-old daughter had hypothyroidism, a small thyroid gland, and negative
      results of pentagastrin stimulation testing of calcitonin. The 18-year-old
      grandson also had a negative pentagastrin test result and normal thyroid
      ultrasound findings. The 5-year-old granddaughter had normal results of thyroid
      ultrasonography. In all patients, we recommended thyroidectomy. CONCLUSION:
      Prospective studies are needed to clarify which patients with codon 791 RET
      germline mutation should undergo thyroidectomy.

PMID- 15251616
TI  - Once-daily insulin glargine compared with twice-daily NPH insulin in patients
      with type 1 diabetes.
AB  - OBJECTIVE: To present the findings in a randomized, parallel-group study,
      comparing once-daily insulin glargine with twice-daily NPH insulin in patients
      with type 1 diabetes previously treated with multiple daily injections of basal
      and regular insulin. METHODS: Of 394 patients with type 1 diabetes treated for up
      to 28 weeks, 195 received insulin glargine and 199 received NPH insulin, in
      addition to preprandial regular insulin. Glycemic control and hypoglycemic
      episodes were assessed. RESULTS: A greater mean decrease in fasting blood glucose
      (FBG) was achieved at endpoint with insulin glargine than with NPH insulin (-21
      mg/dL versus -10 mg/dL [-1.17 mmol/L versus -0.56 mmol/L]; P = 0.015), and a
      greater percentage of patients treated with insulin glargine reached the target
      FBG (32.6% versus 21.3%; P = 0.015). Similar percentages of patients in both
      treatment groups achieved glycosylated hemoglobin values of 7.0% or less at
      endpoint (insulin glargine, 35.8%; NPH insulin, 35.4%). After the 1-month
      titration phase, the percentage of patients who reported at least one symptomatic
      hypoglycemic event confirmed by a blood glucose value of less than 50 mg/dL (2.8
      mmol/L) was significantly lower with insulin glargine than with NPH insulin
      (73.3% versus 81.7%; P = 0.021). Furthermore, the percentage of patients who
      reported at least one symptomatic hypoglycemic event confirmed by a blood glucose
      value of less than 36 mg/dL (2.0 mmol/L) was significantly lower with insulin
      glargine than with NPH insulin (36.6% versus 46.2%; P = 0.033). CONCLUSION: Once
      daily insulin glargine was at least as effective as twice-daily NPH insulin in
      improving fasting glycemic control and resulted in fewer reported symptomatic
      hypoglycemic events.

PMID- 15251617
TI  - Substitution of pioglitazone for troglitazone in patients with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the clinical utility of pioglitazone therapy in patients
      who previously received troglitazone. METHODS: We undertook an observational
      study involving patients with type 2 diabetes, who were originally treated with
      troglitazone and subsequently converted to pioglitazone therapy. Drug efficacy
      was evaluated by comparing baseline hemoglobin A1c (HbA1c) levels, weight, blood
      pressure, and lipid profiles (during troglitazone treatment) with corresponding
      values 6 months after final pioglitazone dose titration. Drug safety was
      evaluated by review of hepatic enzyme levels and documented reports of side
      effects. RESULTS: The study cohort consisted of 316 patients in whom pioglitazone
      therapy was initiated after they had received troglitazone for at least 1 year.
      Discontinuation of pioglitazone treatment subsequently occurred in 43 patients;
      in 7 additional patients, no follow-up occurred. We found no significant
      difference between baseline and follow-up mean HbA1c values. Aspartate
      aminotransferase levels did not significantly change after 6 months of
      pioglitazone therapy; however, alanine aminotransferase levels increased by a
      statistically significant 3.8 U/L (95% confidence interval, 2.6 to 4.9).
      Pioglitazone treatment was discontinued because of edema in 29 of the 309
      evaluable patients (9.4%). CONCLUSION: Pioglitazone was as effective as
      troglitazone in maintaining HbA1c levels. The hepatic safety of pioglitazone was
      also demonstrated.

PMID- 15251618
TI  - Improvement of sensory impairment in patients with peripheral neuropathy.
AB  - OBJECTIVE: To report the findings in 27 patients with peripheral neuropathy (21
      with lower extremity sensory impairment associated with diabetic peripheral
      neuropathy and 6 with other causes), who received treatment with monochromatic
      near-infrared photoenergy (890 nm) delivered by the Anodyne Therapy System (ATS).
      METHODS: All enrolled patients exhibited abnormal sensory perception (either
      hyperesthesia or hypoesthesia) based on a qualifying examination with the
      Neurometer CPT (current perception threshold) (baseline CPT). The patients
      received 10 ATS treatments (each lasting 40 minutes) during a 2-week period and
      then underwent CPT retesting to determine the extent of improvement of sensory
      impairment in myelinated and unmyelinated sensory fibers of the peroneal nerve.
      RESULTS: All patients obtained improvement in sensory impairment in comparison
      with baseline CPT measures, and 16 of the 27 patients achieved normal sensory
      responses in all nerve fiber subpopulations. Ten patients had been tested
      previously (initial CPT) and did not exhibit spontaneous improvement in sensory
      impairment during a mean period of 27 months before baseline CPT. After receiving
      the ATS treatments, however, this group of patients showed improvement in
      comparison with both initial CPT results and baseline CPT. CONCLUSION: On the
      basis of the data from this study, the ATS seems to be a safe and effective
      treatment to improve sensory impairment associated with peripheral neuropathy due
      to diabetes and other causes.

PMID- 15251619
TI  - Changing trends in thyroid practice: understanding nodular thyroid disease.
AB  - OBJECTIVE: To describe changes that have occurred between 1952 and 2002 in the
      evaluation and management of nodular thyroid disease. METHODS: A 30-year personal
      experience, institutional contributions, and the related published literature on
      evaluation of thyroid function and evolving strategies for management of thyroid
      nodules are reviewed. RESULTS: Triiodothyronine (T(3)) was discovered in 1952,
      and measurement of plasma thyroxine by a competitive protein-binding technique
      became available in the 1960s. Late during that decade, the first
      radioimmunoassay for thyroid-stimulating hormone (TSH) was described, modified,
      and then used in clinical practice until the mid-1980s, when the more sensitive
      TSH assays became widely available. T(3) determination by radioimmunoassay was
      introduced early in the 1970s. Currently, sensitive thyroid function tests can
      detect early disease. In the general population, thyroid nodules have a
      prevalence higher than 50% after age 65 years, affecting more than 100 million
      people in the United States. Two important developments influenced thyroid nodule
      evaluation and management-- fine-needle aspiration (FNA) biopsy and
      ultrasonography. Because FNA biopsy has emerged as the most accurate test for
      nodule diagnosis, it has decreased the need for scanning and for thyroidectomy
      and thereby is likely to reduce health-care costs by more than $500 million
      annually in the United States. Thyroid ultrasonography is the imaging method of
      choice for evaluation of thyroid gland structure. Management of cytologically
      benign thyroid nodules remains controversial. CONCLUSION: TSH seems to be only
      one of many factors in pathologic thyroid growth. FNA, because of its diagnostic
      accuracy, should be the initial procedure used in nodule evaluation.

PMID- 15251620
TI  - Severe hyperglycemia during gatifloxacin therapy in patients without diabetes.
AB  - OBJECTIVE: To present two cases of severe hyperglycemia in patients without
      diabetes who received gatifloxacin therapy. METHODS: We describe the histories,
      clinical findings, and hospital courses of two women in whom severe hyperglycemia
      developed after gatifloxacin therapy was initiated. Interacting factors that may
      result in severe hyperglycemia in patients without diabetes and the literature
      explaining the mechanism by which gatifloxacin can alter glucose metabolism are
      reviewed. RESULTS: Our first patient, a 46-year-old woman with end-stage renal
      disease, presented with a 3-day history of fever, abdominal pain, and
      hypotension. Admission laboratory data included a fasting plasma glucose level of
      72 mg/dL and a glycosylated hemoglobin of 5.3%. She was treated with gatifloxacin
      for an infected ovarian cyst found on laparotomy. Her subsequent glucose values
      ranged from 400 to 500 mg/dL and remained high during gatifloxacin therapy.
      Antibiotic treatment was changed to ciprofloxacin. On outpatient follow-up, the
      patient's fasting plasma glucose levels had decreased to a range of 87 to 108
      mg/dL. Our second patient, a 77-year-old woman with a history of chronic renal
      failure and congestive heart failure, was hospitalized because of dyspnea and
      hypotension. She was given gatifloxacin for a urinary tract infection. Her daily
      fasting plasma glucose value gradually increased from 100 mg/dL on admission to
      694 mg/dL on the 6th hospital day. The patient required insulin therapy
      throughout her hospitalization, and she died on the 12th hospital day.
      CONCLUSION: Gatifloxacin therapy may precipitate severe hyperglycemia in patients
      without diabetes, especially in the elderly population, those with renal
      insufficiency, and those receiving multiple drugs known to alter glucose
      metabolism. Discontinuation of gatifloxacin treatment may result in improved
      glucose homeostasis.

PMID- 15251621
TI  - Excision of a mediastinal parathyroid gland with use of video-assisted
      thoracoscopy, intraoperative 99mTc-sestamibi scanning, and intraoperative
      monitoring of intact parathyroid hormone.
AB  - OBJECTIVE: To report the complementary use of video-assisted thoracoscopic
      surgery (VATS) and intraoperative 99mTc-sestamibi scanning for persistent
      secondary hyperparathyroidism due to a mediastinal supernumerary parathyroid
      gland. METHODS: We describe a patient with recurrent secondary
      hyperparathyroidism attributable to a mediastinal parathyroid gland who underwent
      parathyroidectomy with use of VATS, intraoperative 99mTc-sestamibi scanning
      (gamma probe), and intraoperative monitoring of intact parathyroid hormone
      (iPTH). RESULTS: A 32-year-old man with chronic renal failure who had undergone a
      4-gland parathyroidectomy with autotransplantation 14 years previously presented
      with symptomatic hypercalcemia. A preoperative single-photon emission computed
      tomographic (SPECT) sestamibi scan revealed a focus of mediastinal uptake,
      suggestive of an intrathymic gland. The patient underwent a cervical exploration,
      and the previously reimplanted parathyroid gland and the thymus were resected.
      iPTH levels failed to normalize, and the operation was terminated. A repeated
      SPECT scan again revealed an area of mediastinal uptake. Computed tomographic
      scan of the chest showed a mediastinal gland adjacent to the aortic arch. VATS
      and intra-operative sestamibi scanning aided in localization of the ectopic
      parathyroid gland. After removal of the hyperplastic gland, iPTH levels decreased
      appropriately. CONCLUSION: In reoperative parathyroidectomy involving mediastinal
      glands, VATS, complemented by gamma probe localization and iPTH monitoring, may
      be used to minimize the operative dissection needed to cure hyperparathyroidism.

PMID- 15251622
TI  - Severe autoimmune hypoglycemia with insulin antibodies necessitating
      plasmapheresis.
AB  - OBJECTIVE: To report a case of autoimmune hypoglycemia. METHODS: We describe the
      clinical course of a patient with autoimmune hypoglycemia, including results of
      biochemical and histocompatibility antigen studies, as well as the therapeutic
      intervention and follow-up. RESULTS: A 77-year-old man presented with clinical
      manifestations of severe spontaneous hypoglycemia associated with extremely high
      levels of insulin (>300 mU/mL) and insulin antibodies (>100 U/mL) without any
      exogenous insulin administration. He had no other associated autoimmune disorder
      or exposure to the sulfhydryl group of drugs. Corticosteroid therapy was
      initiated, but the patient continued to have hypoglycemia and required
      plasmapheresis. The hypoglycemia resolved after plasmapheresis. During follow-up,
      the patient was treated with prednisone, the dose of which was tapered gradually.
      The insulin antibodies, which had decreased rapidly after plasmapheresis,
      gradually disappeared within a few months. The patient remained free of
      hypoglycemia as well as insulin antibodies 11 months after corticosteroid therapy
      was discontinued. CONCLUSION: Although autoimmune hypoglycemia is an uncommon
      disorder, it should be considered in any patient with hypoglycemia in the setting
      of nonsuppressed insulin levels associated with insulin antibodies.

PMID- 15251623
TI  - Adrenal insufficiency attributable to adrenal hemorrhage: long-term follow-up
      with reference to glucocorticoid and mineralocorticoid function and replacement.
AB  - OBJECTIVE: To describe the long-term follow-up of acute adrenal insufficiency
      attributable to bilateral adrenal hemorrhage. METHODS: We performed a
      retrospective review of medical records of four patients who underwent follow-up
      for 6(1/2) to 19 years. RESULTS: Despite published reports of more than 500
      patients with bilateral massive adrenal hemorrhage through 2001, no long-term
      data assessing the continuing requirements for glucocorticoid and
      mineralocorticoid replacement are available. After follow-up of four patients
      with acute bilateral adrenal hemorrhage and glucocorticoid insufficiency for
      6(1/2) to 19 years, we document the absence of need for long-term
      mineralocorticoid replacement on the basis of no occurrence of postural
      hypotension, normal electrolytes, normal baseline or cosyntropin-stimulated serum
      aldosterone levels, and generally, though not invariably, normal plasma renin
      activity levels. We further document the improvement in either or both baseline
      and cosyntropin-stimulated serum cortisol levels in three of the four patients
      and the ability of one patient to function normally without cortisol replacement
      for 4 years. Adrenal histologic findings in this last-mentioned patient revealed
      previously undescribed changes consistent with regeneration and myelolipoma.
      Finally, we confirm bilateral atrophic adrenal glands by computed tomography
      5(1/2) to 11(1/2) years after bilateral adrenal hemorrhage in three of the four
      patients. CONCLUSION: Long-term follow-up of patients with acute adrenal
      insufficiency attributable to adrenal hemorrhage demonstrates, for the first
      time, absence of need for prolonged mineralocorticoid replacement and some
      improvement in endogenous glucocorticoid function in at least some of these
      patients.

PMID- 15251624
TI  - Follicular thyroid cancer presenting as a sellar mass: case report and review of
      the literature.
AB  - OBJECTIVE: To describe an uncommon initial manifestation of well-differentiated
      follicular carcinoma of the thyroid in an unusual metastatic site. METHODS: We
      present clinical, laboratory, and imaging findings in our patient and review
      related data from the literature. RESULTS: A young healthy woman presented with
      headache and diplopia. Magnetic resonance imaging of the brain showed a complex
      mass in the sellar region. Endocrine evaluation was remarkable only for a
      modestly high serum prolactin level. Transsphenoidal biopsy of the sellar mass
      revealed metastatic follicular thyroid carcinoma. On subsequent examination, a
      thyroid nodule was palpated. She underwent total thyroidectomy and ablative
      therapy with 131I, after which her symptoms gradually subsided and the sellar
      mass ultimately decreased in size. Although well-differentiated thyroid cancer
      generally manifests as a thyroid nodule, metastatic disease is present at the
      time of initial assessment in approximately 1% of cases, and the lungs and the
      skeleton are the most frequent sites of involvement. Only a few cases of thyroid
      cancer metastasizing to the sella have been reported. Described cases occurred
      mainly in elderly patients with previously diagnosed thyroid cancer. The most
      common malignant tumors that metastasize to the sella and pituitary are lung
      cancer in men and breast cancer in women. Metastatic tumors frequently manifest
      with cranial nerve palsies or diabetes insipidus and occur in elderly patients.
      CONCLUSION: Follicular thyroid cancer can manifest initially as a distant
      metastatic tumor in young patients. Metastatic lesions should always be in the
      differential diagnosis of a sellar mass, even in young patients.

PMID- 15251625
TI  - Blood glucose monitoring technology: translating data into practice.
AB  - OBJECTIVE: To describe how blood glucose software downloading has been
      successfully incorporated into a clinical practice by focusing on key data-
      frequency of testing, blood glucose averages, and standard deviations. METHODS:
      The development of self-monitoring of blood glucose, including the spectrum of
      blood glucose monitors and diabetes management software programs, is reviewed,
      and clinical applications in specific cases are presented. RESULTS: Since the
      1980s, motivated patients with diabetes have used portable meters to monitor
      their blood glucose levels. The practice became a standard of care in 1993, when
      the Diabetes Control and Complications Trial demonstrated that maintaining near
      normal glycemic levels could prevent or delay the long-term complications of type
      1 diabetes. Since then, the technology of blood glucose monitoring has burgeoned-
      an array of memory meters and downloading software offers clinicians and patients
      more information than ever before. Yet, because health-care providers and
      patients are often at a loss to interpret and apply the resulting plethora of
      data, few take full advantage of the latest technology. Important insights are
      shared about certain downloaded information from glucose meters that will help
      improve or maintain glycemic control. CONCLUSION: Data downloaded from glucose
      meters can be used in conjunction with written records in logbooks to evaluate
      glucose patterns and formulate more precise and efficacious therapeutic regimens.

PMID- 15251626
TI  - American College of Endocrinology position statement on inpatient diabetes and
      metabolic control.

PMID- 15251627
TI  - Multiple endocrine neoplasia type 1 manifesting with chronic and persistent
      diarrhea.

PMID- 15251628
TI  - You can call me doctor.

PMID- 15251629
TI  - Gatifloxacin-induced hyperglycemia.

PMID- 15251630
TI  - Visual vignette. Acute parathyroid crisis due to primary hyperparathyroidism.

PMID- 15251631
TI  - Visual vignette. Profound primary hypothyroidism.

PMID- 15251632
TI  - Proceedings of the American College of Endocrinology Task Force on Inpatient
      Diabetes and Metabolic Control Consensus Conference. Washington, DC, USA,
      December 2003.

PMID- 15251633
TI  - American College of Endocrinology position statement on inpatient diabetes and
      metabolic control.

PMID- 15251634
TI  - Current standards of care for inpatient glycemic management and metabolic
      control: is it time for definite standards and targets?
AB  - OBJECTIVE: To review the available literature on the presence of diabetes in the
      inpatient population and its effect on outcomes. RESULTS: Diabetes is a
      progressively worsening epidemic in the United States. Patients with diabetes
      have a disproportionate representation among the inpatient population in this
      country, and their share of total health-care costs is both disproportionate and
      growing rapidly. Patients with diabetes are often admitted to the hospital not
      primarily because of their diabetes but rather because of the need for treatment
      of the end-stage complications of diabetes, such as cardiovascular,
      cerebrovascular, and peripheral vascular disease as well as diabetic nephropathy
      and retinopathy, or because of unrelated illnesses for which diabetes is a
      complication. Diabetes is a frequent comorbid condition and increases the
      duration of hospitalization by 1 to 2 days. Numerous organizations have issued
      guidelines for outpatient diabetes management and metabolic control and have
      updated them periodically; however, no such guidelines or standards have been
      formulated for inpatient diabetes management. CONCLUSION: In view of a rapidly
      growing body of evidence suggesting that enhanced glycemic control decreases
      morbidity and mortality in patients with hyperglycemia, such as those with new
      onset diabetes, as well as in patients with previously established diabetes, the
      creation of clearly defined standards and targets for inpatient management of
      hyperglycemia and metabolic control seems important for improvement of outcomes
      in hospitalized patients with diabetes.

PMID- 15251635
TI  - Role of insulin-glucose infusion in outcomes after acute myocardial infarction:
      the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI)
      study.
AB  - OBJECTIVE: To review the Diabetes and Insulin-Glucose Infusion in Acute
      Myocardial Infarction (DIGAMI) study for findings regarding effects on morbidity
      and mortality. RESULTS: The DIGAMI trial was an intervention study that tested
      the hypothesis that initial intensive metabolic control by insulin-glucose
      infusion for at least 24 hours followed by long-term treatment with
      subcutaneously administered insulin improved the prognosis in patients with
      diabetes and acute myocardial infarction. Overall, the intensive approach reduced
      the long-term relative mortality (at 3.4 years of follow-up) by 25% in the
      insulin-treated group. Improved long-term survival was especially evident in the
      prestratified group of patients without prior insulin treatment, in whom the 3.4
      year mortality reduction was 45%. Furthermore, a close correlation was noted
      between high blood glucose level at admission and mortality among the patients in
      the control group; this relationship was attenuated by intensive insulin
      treatment. CONCLUSION: The DIGAMI study supports the theory that intensive
      metabolic care in patients with diabetes who have had an acute myocardial
      infarction improves the prognosis. The study, however, could not answer whether
      this result was due to the initial insulin-glucose infusion or to the long-term
      subcutaneous treatment with insulin. This question is currently being addressed
      in the DIGAMI-2 study.

PMID- 15251636
TI  - Role of intravenous insulin therapy in critically ill patients.
AB  - OBJECTIVE: To summarize the novel evidence for maintaining normoglycemia with
      intensive insulin therapy during intensive care in critically ill patients, with
      or without diabetes, in the surgical intensive-care unit. RESULTS: Although the
      association between hyperglycemia and adverse outcomes of trauma or surgical
      procedures necessitating intensive care was known, only one intervention study
      has investigated the causality of this association. This study showed that tight
      blood glucose control with insulin, aiming for strict normoglycemia (80 to 110
      mg/dL or 4.5 to 6.1 mmol/L) during intensive care, dramatically decreased
      morbidity and mortality. The clinical benefits were present whether or not
      patients had previously diagnosed diabetes, and they seemed independent of
      severity and type of critical illness. Multivariate logistic regression analysis
      indicated that metabolic control, rather than insulin dose per se, statistically
      explains the beneficial effects of intensive insulin therapy on outcomes of
      critical illness. Other metabolic effects besides blood glucose control, however,
      such as normalization of dyslipidemia, and immunologic effects, such as
      suppression of excessive inflammation and improvement of macrophage function,
      accompany glycemic control in critically ill patients. These effects seem to
      surpass the level of glycemic control in explaining the clinical benefits of
      intensive insulin therapy on sepsis, organ failure, and death. Ongoing studies
      are attempting to clarify the mechanisms that underlie the beneficial effects of
      this simple and cost-saving intervention. CONCLUSION: The available evidence
      favors targeting normoglycemia (blood glucose levels of less than 110 mg/dL or
      6.1 mmol/L) by insulin infusion in all adult surgical intensive-care patients.
      Whether these findings are applicable to nonsurgical intensive-care or to
      pediatric patients in the intensive care unit remains unclear.

PMID- 15251637
TI  - Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes
      of cardiac surgical procedures: the Portland Diabetic Project.
AB  - OBJECTIVE: To describe the main findings of the Portland Diabetic Project, which
      elucidates the adverse relationship between hyperglycemia and outcomes of cardiac
      surgical procedures in patients with diabetes and delineates the protective
      effects of intravenous insulin therapy in reducing those adverse outcomes.
      RESULTS: In this ongoing 17-year prospective, nonrandomized, interventional study
      of 4,864 patients with diabetes who underwent an open-heart surgical procedure,
      we investigated the effects of hyperglycemia, and its subsequent reduction by
      continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing
      blood glucose levels were found to be directly associated with increasing rates
      of death, deep sternal wound infections (DSWI), length of hospital stay (LOS),
      and hospital cost. In separate multivariate analyses, increasing hyperglycemia
      was found to be independently predictive of increasing mortality (P<0.0001), DSWI
      (P = 0.017), and LOS (P<0.002). Conversely, CII therapy, designed to achieve
      predetermined target blood glucose levels, independently reduced the risks of
      death and DSWI by 57% and 66%, respectively (P<0.0001 for both). Target blood
      glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII
      therapy are both important variables that determine the effect of the CII therapy
      on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%)
      and DSWI rates (0.8%) in patients with diabetes were normalized to those of the
      nondiabetic population by the use of the Portland CII Protocol. CONCLUSION:
      Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure
      affects biochemical and physiologic functions, which, in turn, adversely alter
      mortality, LOS, and infection rates. The Portland CII Protocol is a cost
      efficient method that effectively eliminates hyperglycemia and reduces
      postoperative morbidity and mortality in patients with diabetes undergoing an
      open-heart operation. CII protocols should be the standard care for
      glycometabolic control in all patients undergoing cardiac surgical procedures.

PMID- 15251638
TI  - Effect of hyperglycemia on stroke outcomes.
AB  - OBJECTIVE: To review published data about the relationship between hyperglycemia
      and the outcome of patients with stroke. RESULTS: Stroke is the most frequent
      cause of permanent disability in the Western world and the third leading cause of
      death among Americans. Each year, more than 500,000 Americans have a
      cerebrovascular accident. In the medical literature, numerous reports have
      discussed how hyperglycemia during acute stroke, regardless of a patient's prior
      diabetes status, has been associated with significantly higher morbidity, higher
      mortality, longer hospital stays, reduced long-term recovery, and diminished
      ability to return to work. In the United States alone, an estimated $300 million
      in additional health-care costs are incurred among hospitalized patients with
      stroke who also have high blood glucose levels. Treatment of hyperglycemia has
      safely, successfully, and effectively yielded glucose levels in the normal range
      in the hospital setting under the direction of specialty physicians and should be
      implemented in patients with stroke. CONCLUSION: Until convincing randomized
      prospective trials prove that tight glycemic control does not improve stroke
      outcomes, the overwhelming preponderance of data suggests that aggressive glucose
      management should be the standard care in all patients with stroke and
      hyperglycemia.

PMID- 15251639
TI  - Glucose and insulin requirements during labor and delivery: the case for
      normoglycemia in pregnancies complicated by diabetes.
AB  - OBJECTIVE: To present protocols for maintaining normoglycemia during labor and
      delivery in order to achieve optimal outcomes of pregnancy in women with
      diabetes. RESULTS: Labor has a glucose-lowering effect. In the case of women with
      insulin-requiring gestational diabetes, no additional insulin is needed with the
      onset of labor; sufficient glucose should be infused to keep such women from
      becoming ketotic from the pronged period of starvation. Likewise, protocols
      derived from glucose-controlled insulin infusion studies reveal that women with
      type 1 diabetes require no more subcutaneously administered insulin on the
      morning of an induction of labor or at the onset of spontaneous labor. The
      intravenously administered solutions should be started with isotonic saline or
      electrolyte solutions. As soon as active labor is achieved, the solutions should
      be switched to a glucose-containing fluid and administered at a rate of 2.55
      mg/kg per minute. CONCLUSION: Labor is a form of exercise and thus obviates the
      insulin requirement in women with all types of diabetes, but it also necessitates
      an eightfold increase in glucose substrate in order to prevent maternal
      hypoglycemia and ketosis. The literature presents clear evidence that neonatal
      hypoglycemia is directly related to maternal hyperglycemia during labor and
      delivery. Thus, protocols for maintaining normoglycemia during labor and delivery
      are necessary to achieve optimal results.

PMID- 15251640
TI  - Reduction of nosocomial infections in the surgical intensive-care unit by strict
      glycemic control.
AB  - OBJECTIVE: To investigate whether hyperglycemia in glucose-intolerant patients
      without diabetes could lead to increased nosocomial infections in the surgical
      intensive-care unit (ICU). METHODS: A prospective, randomized, controlled
      clinical trial was conducted in the surgical ICU of a large teaching hospital in
      Hartford, Connecticut. Adult patients admitted to a 12-bed surgical ICU requiring
      treatment of hyperglycemia (glucose values > or = 140 mg/dL) were randomly
      assigned to receive standard insulin therapy (target glucose range, 180 to 220
      mg/dL) or strict insulin therapy (target glucose range, 80 to 120 mg/dL)
      throughout their ICU stay. Demographic data, comorbidities, and confounding
      variables were analyzed. Outcome measures included mean daily serum glucose
      values, mean daily insulin doses, and number of nosocomial infections during the
      ICU stay. RESULTS: The study was completed by 61 critically ill surgical patients
      (27 in the standard glucose control group and 34 in the strict glucose control
      group). A significant reduction (P<0.001) in mean daily glucose level was
      achieved in the strict glycemic control group (125 +/- 36 mg/dL) in comparison
      with the standard glycemic control group (179 +/- 61 mg/dL). Furthermore, a
      significant reduction (P<0.05) in the incidence of total nosocomial infections,
      including intravascular device, bloodstream, intravascular device-related
      bloodstream, and surgical site infections, was observed in the strict glucose
      control group in comparison with the standard glucose control group. The
      incidence of hypoglycemia (glucose levels <60 mg/dL) was significantly increased
      (P<0.001) in the strict glycemic control group in comparison with the standard
      glycemic control group (32% versus 7.4% of patients or 0.8% versus 0.1% of total
      serum glucose values, respectively). CONCLUSION: Strict glycemic control is a
      safe and effective method for reducing the incidence of nosocomial infections in
      a predominantly nondiabetic, general surgical ICU patient population.

PMID- 15251641
TI  - Reduction of hospital costs and length of stay by good control of blood glucose
      levels.
AB  - OBJECTIVE: To discuss the available literature regarding the potential benefits
      of improving blood glucose control in hospitalized patients. RESULTS: Subjects
      with diabetes constitute an increasing proportion of hospitalized patients.
      Hospital costs attributable to diabetes are in excess of $40 billion annually in
      the United States. Numerous reports have confirmed a correlation between blood
      glucose control at the time of hospitalization and adverse inpatient outcomes for
      various admission diagnoses, in some cases with or without a previous diagnosis
      of diabetes. Several studies have specifically found a relationship between
      improved inpatient control of blood glucose levels and decreased hospital length
      of stay. Likewise, cost savings have been proposed for intensive inpatient
      glucose management for a few critical admission diagnoses. Although the apparent
      economic advantage of aggressive control of blood glucose levels is substantial,
      cost-effectiveness analyses have been few and limited in scope. CONCLUSION:
      Improved blood glucose control in the hospital setting appears to reduce the
      duration of hospital stay and the hospital costs. Comprehensive analyses of cost
      effectiveness through prospective, randomized intervention trials are needed,
      however, to characterize these benefits more precisely.

PMID- 15251642
TI  - Molecular mechanisms by which metabolic control may improve outcomes.
AB  - OBJECTIVE: To summarize available evidence providing potential explanations for
      metabolic and nonmetabolic abnormalities during conditions of acute stress and
      possible mechanisms whereby insulin therapy may affect these changes. RESULTS:
      Recent studies have demonstrated a remarkable effect of intensive insulin therapy
      and reductions in morbidity and mortality in patients in intensive-care units and
      other hospital settings. The mechanisms involved in these effects are under
      thorough investigation. Insulin therapy improves glucose and lipid homeostasis,
      both of which are deleterious to the tissues, especially during severe stress. In
      addition, insulin has direct effects on the levels of inflammatory cytokines and
      other proteins that may influence the overall outcome of patients undergoing
      various stressful conditions. CONCLUSION: Analysis of published studies suggests
      that the beneficial effects of insulin therapy may be derived from both direct
      and indirect mechanisms.

PMID- 15251643
TI  - Effect of insulin therapy on nonglycemic variables during acute illness.
AB  - OBJECTIVE: To review the possible mechanisms for the reported clinical finding of
      better outcomes for hospitalized and critically ill patients as the result of
      improved metabolic control. RESULTS: Insulin inhibits free fatty acids,
      proinflammatory cytokines, and inflammatory growth factors, all of which may be
      detrimental in critically ill patients. Furthermore, insulin enhances nitric
      oxide synthesis, which promotes vasodilation. The mechanisms of insulin
      regulation of these factors are complex, although insulin seems to have a direct
      effect on the transcriptional factor, nuclear factor-kappabeta (NF-kappabeta). In
      turn, NF-kappabeta modulates the proinflammatory cytokines, adhesion molecules,
      and chemokines. In a euglycemic or slightly hyperglycemic environment, NF
      kappabeta is suppressed by insulin; however, with more profound hyperglycemia, NF
      kappabeta is induced and the proinflammatory cytokines are thus increased.
      CONCLUSION: Although considerable research must be completed to identify the
      apparent relationship between stringent metabolic control and improved outcomes
      in acutely ill patients, current evidence suggests that both the treatment
      (glucose-insulin-potassium infusion) and the resultant plasma glucose
      concentrations may be independent important components of the underlying
      mechanisms.

PMID- 15251644
TI  - Intravenous insulin infusion therapy: indications, methods, and transition to
      subcutaneous insulin therapy.
AB  - OBJECTIVE: To describe indications for intravenous (IV) insulin infusion therapy
      and glycemic thresholds, discuss methods and protocols, and promote use of and
      access to IV insulin infusion therapy for all appropriate patients in the
      hospital setting. RESULTS: Randomized, prospectively designed trials support the
      use of IV insulin infusion therapy for patients in the surgical intensive-care
      unit, including postoperative cardiac patients and patients having myocardial
      infarction. Among patients in the surgical intensive-care unit, reanalysis of the
      data suggested no threshold at which benefit occurred above the blood glucose
      level of 110 mg/dL. In another study, retrospective analysis of data among
      critically ill medical and surgical patients suggested a target blood glucose
      level of 145 mg/dL or less. In other populations, the threshold or ideal target
      blood glucose range has not been determined. Three protocols for IV insulin
      infusion are described that maintain blood glucose levels safely below the upper
      limit of their respective target ranges without substantial risk of hypoglycemia.
      CONCLUSION: The threshold for initiation of IV insulin infusion is 110 mg/dL for
      critically ill surgical patients, 140 mg/dL for other medical or surgical
      patients, 180 mg/dL for patients in whom subcutaneous insulin regimens fail, and
      100 mg/dL for pregnant women. The blood glucose target range is 80 to 110 mg/dL
      for selected critically ill surgical patients, 70 to 100 mg/dL for pregnant
      women, and 90 to 140 mg/dL for all other patients. Hospitals should develop
      procedures to make IV insulin infusion therapy available to all appropriate
      patients.

PMID- 15251645
TI  - Subcutaneous insulin therapy in the hospital setting: issues, concerns, and
      implementation.
AB  - OBJECTIVE: To summarize issues and recommendations regarding subcutaneous insulin
      therapy in various clinical settings in the hospital. RESULTS: The inpatient
      insulin regimen must be tailored to the specific clinical circumstance of the
      individual patient. Because nutritional intake is not necessarily provided as
      discrete meals in the hospital, the insulin dose requirement can be subclassified
      into "basal" and "nutritional" needs. In addition, the insulin requirement is
      generally increased in the presence of acute illness and stress. Thus, components
      of the insulin requirement are divided into basal, nutritional, and correction
      insulin. When the physician writes insulin orders, the basal and nutritional
      components are written as programmed or scheduled insulin, and the correction
      dose insulin is written as an algorithm to supplement the scheduled insulin.
      Total insulin requirements may vary widely. Practical guidelines and suggestions
      are presented for selection of appropriate insulins, the delivery route, and the
      logical apportionment to programmed and correction insulin doses for hospitalized
      patients who are eating or not eating. Moreover, the role of bedside blood
      glucose monitoring in the hospital setting is discussed. CONCLUSION: Strict
      glycemic management in hospitalized patients has been shown to improve outcomes.
      Development and implementation of specific strategies for insulin delivery and
      improved methods for blood glucose monitoring should help to achieve target blood
      glucose levels safely.

PMID- 15251646
TI  - Hospital hypoglycemia: not only treatment but also prevention.
AB  - OBJECTIVE: To propose a strategy, applicable on general hospital wards, for
      prevention of hypoglycemia in hospitalized patients. RESULTS: Although the
      mortality rate among hospitalized patients with hypoglycemia has been shown to be
      22.2 to 27% in series that included patients with diabetes, some investigators
      have shown that hypoglycemia is not an independent predictor of mortality.
      Outside the critical care setting, the comparative risks of hyperglycemia and
      hypoglycemia and the relationship of hospital hypoglycemia to intensification of
      glycemic control have not been determined. The reported incidence of hospital
      hypoglycemia ranges from 1.2% for hospitalized adults to 20% for nonpregnant
      patients with diabetes admitted without a metabolic emergency. Among patients
      receiving antihyperglycemic therapy, the literature describes precipitating
      events--usually a sudden change of caloric exposure-- and predisposing conditions
      for hypoglycemic episodes. CONCLUSION: Hospital hypoglycemia is predictable, and
      it is preventable by measures other than undertreatment of hyperglycemia.
      Physician orders for antihyperglycemic therapy should be written and, if
      necessary, be revised so as to respond to the presence of predisposing conditions
      for hypoglycemia. A ward-based protocol or hospital-wide policy should establish
      the appropriate response to triggering events. Within the time frame of action of
      previously administered antihyperglycemic drugs (after abrupt interruption of
      caloric exposure), the threshold for preventive intravenous administration of
      dextrose is a glucose concentration of 120 mg/dL.

PMID- 15251647
TI  - A systems approach to reducing errors in insulin therapy in the inpatient
      setting.
AB  - OBJECTIVE: To highlight the importance of insulin-related medical errors in
      causing poor outcomes in a hospital setting and to propose a systems approach for
      improvement. RESULTS: Evidence reported in the medical literature has identified
      insulin therapy errors as a large and clinically important problem. Insulin has
      been labeled as one of the top five "high-risk medications" in the inpatient
      setting. Although insulin therapy can be lifesaving in the hospital setting, it
      can be life-threatening if used inappropriately. Widespread major systemic
      problems, such as heavy patient loads for physicians and nurses, absence of
      backup checks in critical areas, defective communication and coordination,
      illegible handwriting, and unawareness of the importance of blood glucose
      control, create obstacles to appropriate and safe care of patients receiving
      insulin in the hospital. With thorough analysis of the setting, additional
      training, collective establishment of goals focused on patient safety, insertion
      of backup checks in areas susceptible to errors, encouragement of sharing of key
      clinical information, and, where possible, implementation of electronic medical
      records, systemic and knowledge-based problems will be minimized and outcomes
      will improve in insulin-treated hospitalized patients. CONCLUSION: Analysis and
      redesign of systems to develop a "culture of safety" will ultimately reduce
      insulin-related medical errors, provide a safe inpatient environment, and yield
      better outcomes.

PMID- 15251651
TI  - Classification of type 2 diabetes by clinical response to metformin-troglitazone
      combination and C-Peptide criteria.
AB  - OBJECTIVE: To assess the ability of basal and stimulated C-peptide levels and
      stimulated glucose values after oral administration of glucose to predict a
      successful response to metformin and troglitazone combination therapy after
      discontinuation of insulin therapy. METHODS: At the onset of the study, plasma
      glucose and C-peptide levels were measured in a group of 64 obese patients with
      insulin-treated type 2 diabetes while they were fasting and 2 hours after a
      challenge of 100 g of glucose administered orally. Then combination metformin
      troglitazone treatment was initiated while insulin therapy was gradually tapered
      over 8 to 12 weeks. Subjects who successfully tolerated insulin withdrawal after
      the metformin-troglitazone combination were categorized as non-insulin-requiring
      responders, whereas those who needed insulin to obtain glycemic control were
      categorized as insulin-requiring nonresponders. Basal and glucose-stimulated C
      peptide levels as well as stimulated glucose values were contrasted in the
      responder versus nonresponder groups. In a second protocol, eight obese patients
      with insulin-treated type 2 diabetes who successfully stopped insulin therapy
      were reassessed for C-peptide and glucose variables during the 2-hour oral
      glucose tolerance test. This reassessment followed a 12-week period of therapy to
      determine whether treatment of insulin resistance with the combination of
      metformin and troglitazone could normalize the impaired glucose tolerance in type
      2 diabetes. RESULTS: After metformin-troglitazone therapy, 48 study subjects
      (75%) could later be managed without insulin, whereas 16 (25%) needed insulin to
      achieve acceptable glycemic control. In a comparison of the non-insulin-requiring
      responder and insulin-requiring nonresponder groups, the responder group had
      significantly higher glucose-stimulated C-peptide levels and much lower
      stimulated glucose levels. The mean basal plasma C-peptide level was higher in
      the responder than in the nonresponder group, but a small degree of overlap was
      found between the two groups. Combination treatment with metformin and
      troglitazone for 12 weeks resulted in a significant reduction in the C-peptide
      response and glucose variables after the glucose load. CONCLUSION: The results of
      this study indicate that stimulated C-peptide and glucose levels may be useful
      criteria to identify whether combination metformin-troglitazone treatment can
      successfully replace insulin therapy in the management of obese patients with
      type 2 diabetes. Inability to normalize glucose intolerance after restoring
      insulin resistance with insulin sensitizers is supportive of the presence of both
      disturbed beta-cell function and insulin resistance in patients with type 2
      diabetes.

PMID- 15251652
TI  - Characterization of patients in a medical endocrine-based center for male sexual
      dysfunction.
AB  - OBJECTIVE: To characterize the patient population in a multidisciplinary sexual
      dysfunction clinic whose focal person is an endocrinologist and to summarize the
      initial manifestations, the demographics of the study group, and their associated
      medical conditions. METHODS: We undertook a retrospective analysis of the medical
      records of all new consultations in a center for sexual function during a recent
      2-year period. RESULTS: During the period from July 1995 to July 1997, 1,050 men
      were seen in new consultations for sexual dysfunction at our medical facility,
      and complete medical records could be retrieved for 990 of them. Of the overall
      study group of 990 men, most (93.2%) had erectile dysfunction (versus libido or
      ejaculatory problems), but combinations of problems were common. Most men had
      organic causes of their sexual dysfunction that correlated with increasing age;
      however, their dysfunction was more often the result of chronic medical
      conditions than of advancing age itself. Most men were married (72.1%) and in
      long-term relationships (mean duration, more than 20 years). Hypogonadism was the
      most common medical condition (36.3%), a finding that reflected an endocrine
      referral bias. Testosterone treatment alone corrected the complaints in a
      minority of patients. Hypertension was a more common diagnosis than diabetes
      (35.8% versus 23.1%), and pituitary tumors were rare. Successful outcomes were
      achieved in about two-thirds of men having a strong organic cause of sexual
      dysfunction, but treatments were less successful when pronounced psychologic
      factors were present. The patient dropout rate was substantial and was similar in
      each of the four 6-month quarters--an indication that even as newer therapies
      became available, dissatisfaction was still evident. CONCLUSION: Many patients
      have more than one manifestation of sexual dysfunction, which may have to be
      addressed separately. In a sexual dysfunction clinic managed by an
      endocrinologist, referral bias may direct more patients with hypogonadism and
      fewer patients who have had transurethral retropubic prostatectomy or a radical
      prostatectomy. Treatment of hypogonadism corrects sexual dysfunction in only a
      few men, and only when other medical problems are not present. Although the
      percentage of men with diabetes would be expected to be high in this study, the
      number of patients with hypertension was higher. A considerable dropout rate
      during evaluation and treatment persisted throughout this study.

PMID- 15251653
TI  - Serum testosterone levels and reference ranges in reproductive-age women.
AB  - OBJECTIVE: To determine the levels of serum testosterone and
      dehydroepiandrosterone sulfate (DHEAS) in women with no clinical signs of
      hyperandrogenism and no history of glucocorticoid or oral contraceptive use and
      to compare these levels with the reference ranges provided by commercial
      laboratories. METHODS: We undertook a cross-sectional retrospective study of 271
      reproductive-age women encountered at an endocrinology clinic for complaints of
      potential thyroid problems. Serum testosterone and DHEAS levels were determined,
      and statistical analyses were performed. RESULTS: The serum testosterone level in
      women with no acne, hirsutism, or menstrual dysfunction was 14.1 +/- 0.9 ng/dL
      (mean +/- standard error of the mean) (95% confidence interval [CI] = 12.4 to
      15.8). This group was considered our study reference population. In women with
      menstrual dysfunction but no acne or hirsutism, the mean testosterone level was
      significantly higher (17.9 +/- 1.1 ng/dL; 95% CI = 15.7 to 20.0; P<0.002); with
      mild hirsutism, it further increased (38.4 +/- 5.1 ng/dL; 95% CI = 27.4 to 49.4;
      P<0.005); and with moderate to severe hirsutism, it was still higher (49.0 +/-
      2.3 ng/dL; 95% CI = 44.4 to 53.6; P<0.003). Serum DHEAS levels showed similar
      patterns. The upper limit (mean + 2 standard deviations) of testosterone in our
      study reference population was 28 ng/dL, a level that provided a sensitivity of
      84% for detecting hyperandrogenemia. The detection of hyperandrogenemia is
      essentially impossible when the upper limit of the reference range for
      testosterone from commercial laboratories (95 ng/dL) is used. CONCLUSION: The
      testosterone levels reported herein and in the literature for hyperandrogenic
      women both are within the reference (normal) ranges provided by commercial
      laboratories. These observations demonstrate why diagnosis of hyperandrogenemia
      in hyperandrogenic women is difficult when commercial laboratories are used and
      why this condition is not detected in most affected women. Commercial
      laboratories should reevaluate the methods used for establishing their reference
      ranges for serum testosterone.

PMID- 15251654
TI  - Thyroid suppression test with a single oral dose of levothyroxine in the
      diagnosis of functional thyroid autonomy.
AB  - OBJECTIVE: To propose a modified form of thyroid suppression test with use of a
      single oral dose of levothyroxine (35 mg/kg). METHODS: After a baseline
      scintigram, 23 patients with nodular goiter suspected of autonomous function
      (warm or hot nodules, subnormal or undetectable thyrotropin levels, or both
      findings) and 14 normal subjects underwent a repeated scintigram 4 days after
      administration of levothyroxine. We evaluated triiodothyronine (T(3)), free
      thyroxine, and thyrotropin before and on the first, second, third, fourth, and
      seventh days after administration of the individualized dose of levothyroxine.
      RESULTS: The 99th percentile of postsuppression uptake in normal subjects was
      determined, and an uptake >12.4%, a 131 I concentration restricted to the nodule,
      or both factors were adopted as the criteria for diagnosis of an autonomously
      functioning thyroid nodule. Twelve patients were considered to have autonomously
      functioning nodules, and 11 patients were considered to have nonautonomous
      nodules. Baseline thyrotropin levels in patients with autonomous nodules did not
      differ significantly from those in patients with nonautonomous nodules. No signs
      or symptoms of toxicity were detected during the test, but all study subjects had
      increased free thyroxine values, and seven had high levels of T(3). CONCLUSION:
      The thyroid suppression test with 35 mg/kg of levothyroxine is an effective
      method for the diagnosis of an autonomously functioning thyroid nodule, is
      nontoxic, and avoids the inaccurate use of the medication occasionally observed
      with T(3). Even sensitive methods of thyrotropin determination cannot replace
      this test in the evaluation of autonomous thyroid function.

PMID- 15251655
TI  - Life-threatening hypercalcemia associated with primary hyperparathyroidism during
      pregnancy: case report and review of literature.
AB  - OBJECTIVE: To report a case of life-threatening hypercalcemia attributable to
      primary hyperparathyroidism in a pregnant patient and discuss the management of
      severe hypercalcemia during pregnancy. METHODS: We describe a 28-year-old
      pregnant woman who had life-threatening hypercalcemia (serum calcium level of
      25.8 mg/dL). Primary hyperparathyroidism was diagnosed. The patient's management
      and the published medical literature on primary hyperparathyroidism during
      pregnancy are reviewed. RESULTS: Our patient had the highest reported serum
      calcium level that we could find attributable to primary hyperparathyroidism
      during pregnancy. After initial stabilization, parathyroidectomy was successfully
      performed during pregnancy. To our knowledge, this is the first report in which
      this profound degree of hypercalcemia did not result in an adverse maternal or
      fetal outcome. CONCLUSION: Although uncommon, primary hyperparathyroidism during
      pregnancy may be associated with severe maternal and perinatal complications.
      Life-threatening hypercalcemia due to primary hyperparathyroidism during
      pregnancy can be successfully managed surgically during pregnancy, with good
      maternal and fetal outcome.

PMID- 15251656
TI  - Metastatic breast carcinoma mimicking primary thyroid neoplasm in young women.
AB  - OBJECTIVE: To highlight awareness of the potential for breast carcinoma to
      manifest as a thyroid lesion. METHODS: We present two case reports of young women
      with thyroid nodules and discuss diagnostic techniques and treatment strategies.
      RESULTS: In two women, 32 and 38 years old, neither of whom had a history of
      carcinoma, thyroid nodules were suspected clinically of being primary thyroid
      neoplasms. In each case, histopathologic evaluation disclosed that the tumors
      appeared "foreign" to the thyroid and resembled infiltrating duct carcinomas of
      the breast. In some histologically confusing cases, immunostaining for
      thyroglobulin and calcitonin may prove diagnostically helpful. The usual
      treatment for lesions metastatic to the thyroid is surgical resection.
      CONCLUSION: Metastatic breast carcinomas may manifest as primary thyroid lesions,
      especially in women younger than age 40 years.

PMID- 15251657
TI  - Hyperparathyroid crisis manifesting as respiratory and heart failure.
AB  - OBJECTIVE: To describe a case of hyperparathyroid crisis manifesting as
      respiratory failure and congestive heart failure and to emphasize the
      implications of hypercalcemia and hypophosphatemia in this setting. METHODS: A
      case report and a review of the pertinent literature are presented. RESULTS: A 71
      year-old man was transferred to our care because of respiratory failure and
      congestive heart failure. He had no change in cardiorespiratory status until the
      significance of hypercalcemia and hypophosphatemia was recognized and therapy was
      directed at correction of these abnormalities. Primary hyperparathyroidism was
      the cause of these electrolyte abnormalities. CONCLUSION: To our knowledge,
      hyperparathyroid crisis manifesting as respiratory insufficiency and congestive
      heart failure has not been described previously. Phosphate depletion may account
      for the neuromuscular features seen in hyperparathyroidism.

PMID- 15251658
TI  - Single-monthly-dose vitamin D supplementation in elderly patients.
AB  - OBJECTIVE: To determine the serum levels of calcidiol and calcitriol in 2 men and
      in 21 postmenopausal, primarily elderly women receiving hormone replacement
      therapy, orally administered calcium citrate, and an additional supplement of
      50,000 IU of vitamin D (1.25 mg of cholecalciferol) once monthly for various
      periods. METHODS: We determined plasma calcidiol and calcitriol levels at various
      times, ranging from -1 to +60 days after intake of a single dose of 1.25 mg of
      vitamin D in 10 initial or short-term users (1 to 6 months) and in 13 women who
      had been using this monthly regimen for several years. The primary concerns were
      the safety and adequacy of the blood levels achieved with a regimen that
      encouraged compliance. RESULTS: In long-term users of monthly vitamin D regimens,
      calcidiol levels were usually slightly in excess of the upper limit of normal
      (that is, >52 ng/mL [>130 nmol/L]) at all times throughout the month; in
      contrast, calcitriol levels exceeded the normal range (8 to 52 pg/mL [19 to 125
      pmol/L]) only once in 18 samplings. In short-term users, calcidiol levels
      exceeded the normal range only once shortly after intake, and no calcitriol level
      exceeded the normal range. CONCLUSION: Once-a-month dosage of 50,000 IU (1.25 mg)
      of vitamin D in elderly women receiving hormone replacement therapy plus
      supplemental calcium and uncontrolled generic multivitamin intake yields
      calcitriol levels within the normal range, even after years of use of this
      regimen. Calcidiol levels exceeded the normal range at all times in long-term
      users but only once in short-term users. Calcidiol concentrations, however, were
      found to be far below levels (>150 ng/mL [>375 nmol/L]) that might produce
      hypercalciuria or hypercalcemia.

PMID- 15251659
TI  - Variations in adequate levothyroxine replacement therapy in patients with
      different causes of hypothyroidism.
AB  - OBJECTIVE: To compare the levothyroxine replacement dose in 181 patients with
      various causes of hypothyroidism. METHODS: We analyzed the dose of levothyroxine
      used in the following five patient groups: (1) 37 patients with hypothyroidism
      after radioiodine therapy for Graves' thyrotoxicosis who were receiving a stable
      (for at least 4 years) replacement dose (mean time after 131 I therapy, 11.3
      years); (2) 36 patients with Hashimoto's hypothyroidism (chronic autoimmune
      thyroiditis with a goiter or positive test results for antithyroid antibodies);
      (3) 36 patients with central hypothyroidism; (4) 36 patients with hypothyroidism
      after near-total thyroidectomy and 131 I therapy for thyroid carcinoma with
      negative total-body 131 I scans who were euthyroid when receiving levothyroxine;
      and (5) 36 patients with atrophic thyroiditis (no goiter and negative test
      results for antithyroid antibodies). Adequacy of levothyroxine replacement dose
      was defined as a normal thyrotropin level and clinical euthyroidism in patients
      with primary hypothyroidism and a serum free thyroxine index in the upper half of
      the normal range in conjunction with clinical euthyroidism in patients with
      central hypothyroidism. RESULTS: The mean (+/- standard error of the mean)
      replacement dosage of levothyroxine (mg/kg per day) in patients with atrophic
      thyroiditis (1.26 +/- 0.07) was lower (P<0.05) than in patients with Hashimoto's
      hypothyroidism (1.59 +/- 0.07) and those with hypothyroidism after radioiodine
      therapy (1.56 +/- 0.05). These doses, in turn, were lower (P<0.01) than those in
      patients with central hypothyroidism (1.88 +/- 0.10) or euthyroid thyroid
      carcinoma (2.08 +/- 0.07). In a separate analysis, the levothyroxine dose in 43
      patients with hypothyroidism after 131 I treatment was evaluated serially over
      time. The mean levothyroxine dosage increased from 0.87 +/- 0.12 at 6 months
      after 131 I therapy to 1.57 +/- 0.09 at 7 years (P<0.001). The serum thyrotropin
      concentration (in mU/mL) during levothyroxine therapy in patients with central
      hypothyroidism (0.31 +/- 0.08) was lower (P<0.01) than in patients with
      hypothyroidism after 131 I therapy (1.69 +/- 0.37), Hashimoto's hypothyroidism
      (1.39 +/- 0.20), atrophic thyroiditis (1.86 +/- 0.22), and euthyroid thyroid
      carcinoma (1.48 +/- 0.26). CONCLUSION: The levothyroxine replacement dose varies
      with the cause of the hypothyroidism.

PMID- 15251660
TI  - Effects of carbamazepine on the hypothalamic-pituitary-thyroid axis.
AB  - OBJECTIVE: To evaluate the effects of treatment with carbamazepine on the
      hypothalamic-pituitary-thyroid axis and thyroid hormone concentrations in
      patients with epilepsy. METHODS: We undertook a prospective study in seven
      subjects in whom the diagnosis of epilepsy had been established and a regimen of
      carbamazepine (200 mg three times a day) was initiated. All participants
      underwent 24-hour 123 I thyroid uptake studies, as well as assessment of the
      basal thyrotropin concentration and the thyrotropin response to intravenous
      administration of thyrotropin-releasing hormone. In addition, thyroxine (T(4)),
      free T(4) index, triiodothyronine (T(3)), free T(3) index, reverse T(3), and T(3)
      resin uptake were determined before initiation of carbamazepine treatment and
      again after 3 to 4 months of carbamazepine therapy. RESULTS: Serum T(4), T(3),
      and free T(4) index decreased significantly (P<0.05) after therapy with
      carbamazepine, whereas no significant alterations were noted in T(3) resin
      uptake, free T(3) index, and reverse T(3) concentrations. A significant increase
      occurred in basal serum thyrotropin level (P<0.05). Moreover, the peak
      thyrotropin concentration, the absolute change from the basal thyrotropin level,
      and an integrated thyrotropin response expressed as cumulative response to
      thyrotropin-releasing hormone stimulation were all significantly increased after
      carbamazepine therapy in comparison with values documented before initiation of
      therapy (P<0.05 for all comparisons). Finally, 24-hour 123 I uptake by the
      thyroid gland increased slightly after carbamazepine therapy, but the change was
      not statistically significant. All values determined both before and after
      carbamazepine therapy remained within normal ranges. CONCLUSION: Carbamazepine
      therapy induces significant alterations in serum thyroid hormone concentrations
      as well as in the hypothalamic-pituitary-thyroid axis. Nevertheless, patients
      receiving carbamazepine treatment continue to remain euthyroid despite these
      significant changes.

PMID- 15251661
TI  - Role of injection technique in use of insulin pens: prospective evaluation of a
      31-gauge, 8-mm insulin pen needle.
AB  - OBJECTIVE: To evaluate the effectiveness, comfort, and ease of use of insulin pen
      injections with a 31-gauge, 8-mm needle. METHODS: In 50 study subjects (24
      patients with type 1 insulin-dependent diabetes and 26 insulin-using patients
      with type 2 diabetes), we assessed the delivery of insulin, residual insulin
      leakage, glycemic control, plunger depression pressure, and perceived pain
      associated with the B-D 31-gauge, 8-mm pen needles in comparison with the B-D
      conventional 30-gauge, 8-mm pen needles, while the patient used their own insulin
      pens (Novo or B-D). The study subjects injected their usual dose of regular and
      NPH insulin using the 30-gauge, 8-mm needle during the first 3 weeks of the
      study. This period was followed by two 3-week crossover segments of the study
      with either needle assigned in random sequence. RESULTS: No statistically
      significant differences were noted in glycemic control or perceived pain of
      injection between the two needles. The interaction between the two needles and
      the two insulin pen brands on glycemic control was not statistically significant.
      Plunger depression pressure increased with the increase in the gauge of the
      needle and with increases in size of dose of injected insulin (P<0.01). B-D pen
      users reported lower plunger pressure ratings in comparison with Novo pen users
      (P<0.01), regardless of the needle type and dose range. Both the insulin pen type
      and the needle type individually had statistically significant (P<0.01) effects
      on the residual insulin leakage from the needle tip after injection; however,
      their interaction was not statistically significant. Insulin doses greater than
      30 units were associated with increased leakage (P<0.01). As needle retention
      time decreased, residual insulin leakage from the needle tip after injection
      increased (P<0.01), regardless of the needle used. CONCLUSION: The 31-gauge
      insulin pen needles are safe and effective for the delivery of insulin. With both
      30-gauge and 31-gauge needles, attention to injection technique is essential to
      ensure complete delivery of insulin, particularly with administration of large
      doses.

PMID- 15251662
TI  - Evaluation of suppressive therapy for cold thyroid nodules with levothyroxine:
      double-blind placebo-controlled clinical trial.
AB  - OBJECTIVE: To study the efficacy of levothyroxine suppressive therapy in the
      management of benign thyroid nodules. METHODS: We performed a double-blind
      clinical trial comparing levothyroxine treatment (1.5 to 2.0 mg/kg of body weight
      daily) (N = 32) with placebo (N = 30) for a 1-year period in patients with a
      benign, cold thyroid nodule confirmed by biopsy and 99mTc-pertechnetate scanning,
      who were randomly assigned to the treatment or control group. High-resolution
      sonography was used to measure the size of the nodules before and after the
      treatment. Suppression of thyrotropin was evaluated by the administration of
      thyrotropin-releasing hormone to 10 patients randomly in each group. RESULTS: The
      mean volume of the thyroid nodules decreased significantly after 6 months in both
      the levothyroxine group (from 12.8 +/- 11.9 mL to 9.4 +/- 9.8 mL; P = 0.003) and
      the placebo group (from 13.2 +/- 10.2 mL to 11.5 +/- 8.0 mL; P = 0.003). After 12
      months, however, the volume of the nodules had increased. Thus, no significant
      decrease was found in the mean nodule volume in either study group at 1 year in
      comparison with the mean volume at baseline (final mean volume: 12.4 +/- 16.7 mL
      in the levothyroxine group and 11.7 +/- 13.6 mL in the placebo group).
      CONCLUSION: Suppressive therapy with levothyroxine for a period of 12 months
      proved to be ineffective in significantly reducing the size of the thyroid
      nodules in our patients despite effective suppression of the thyrotropin level.

PMID- 15251663
TI  - Thyrotropin-secreting pituitary adenoma responsive to bromocriptine therapy.
AB  - OBJECTIVE: To describe a case of a thyrotropin-secreting pituitary adenoma that
      responded to bromocriptine therapy by suppression of thyrotropin and tumor
      shrinkage. METHODS: We present the clinical course, laboratory data, and
      radiographic findings in a 32-year-old woman with a thyrotropin-secreting
      pituitary adenoma before and after treatment with bromocriptine. RESULTS: The
      patient's pituitary tumor was detected after she had been treated with
      radioactive iodine for thyrotoxicosis presumed to be due to Graves' disease.
      After thyroid ablation, the thyrotropin levels could not be brought into the
      normal range, even while the patient was receiving supraphysiologic doses of
      orally administered levothyroxine. Magnetic resonance imaging of the pituitary,
      along with hormonal workup, confirmed the diagnosis of a thyrotropin-secreting
      pituitary adenoma. Because the tumor was not threatening vital structures and was
      considered incurable by operation, medical therapy was elected. A trial of
      bromocriptine was initiated at 15 mg/day and increased to 30 mg/day in three
      divided doses. Follow-up hormonal studies showed that thyrotropin levels declined
      into the suppressed range, and repeated magnetic resonance imaging scans showed
      substantial shrinkage of the pituitary lesion. CONCLUSION: Thyrotropin-secreting
      tumors may respond hormonally and structurally to bromocriptine therapy. In
      patients with such tumors, a trial of dopamine agonists at high dose may be
      considered before initiation of more invasive medical treatment.

PMID- 15251664
TI  - Sporadic Zollinger-Ellison syndrome with ectopic production of corticotropin:
      surgical management.
AB  - OBJECTIVE: To describe two patients with concurrent Zollinger-Ellison syndrome
      and ectopic production of corticotropin in whom Cushing's syndrome was managed
      surgically. METHODS: Two case vignettes are presented, and a general approach is
      discussed for determining a management strategy for optimal potential for
      survival. RESULTS: The prognosis associated with medical management of patients
      with sporadic Zollinger-Ellison syndrome and Cushing's syndrome attributable to
      ectopic production of adrenocorticotropic hormone (corticotropin) is dismal. Two
      surgical options may yield improved outcomes. The first approach is bilateral
      adrenalectomy followed by replacement therapy with corticosteroids and
      mineralocorticoids. The second surgical approach consists of removal of the organ
      producing the corticotropin (the liver) and performance of hepatic
      transplantation. These two treatment strategies were used in our two patients,
      both of whom had widely metastatic disease at the time of initial assessment. The
      patient who underwent bilateral adrenalectomy continued to do well 4 years
      postoperatively. CONCLUSION: Treatment of patients with Zollinger-Ellison
      syndrome and ectopic production of corticotropin presents a challenge. Because
      results with medical therapy have been suboptimal, aggressive surgical
      intervention seems warranted.

PMID- 15251665
TI  - A case of the Carney triad.
AB  - OBJECTIVE: To report a case of mediastinal paraganglioma in the setting of the
      Carney triad (gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary
      chondroma). METHODS: A case of the Carney triad is presented, and the related
      literature is discussed. RESULTS: A 47-year-old woman with a history of gastric
      leiomyosarcoma and retroperitoneal paraganglioma sought medical attention because
      of progressive shortness of breath. She was found to have a mediastinal mass in
      the aortopulmonary window. The patient had normal blood pressure and normal
      urinary catecholamines, but metaiodobenzylguanidine scintigraphy showed an
      intense uptake in the region of the mass, consistent with paraganglioma. She
      subsequently underwent resection of the mediastinal mass, and the surgical
      pathology report indicated paraganglioma. CONCLUSION: Patients with the Carney
      triad can have multicentric paragangliomas. Metaiodobenzylguanidine scanning may
      be helpful in the diagnostic workup.

PMID- 15251666
TI  - Gender ambiguity in an elderly man.
AB  - OBJECTIVE: To describe the case of an elderly patient with ambiguous genitalia.
      METHODS: We report the clinical features of a 72-year-old man with ambiguous
      genitalia, discuss the possible etiologic factors, and examine the consequences
      of this diagnosis being determined at such a late stage in life. RESULTS: During
      surgical hemicolectomy for colon cancer in a 72-year-old man with a past history
      of hypospadias and hypogonadism, routine exploration of the abdomen and pelvis
      resulted in the discovery and removal of a large, asymptomatic mass, which was
      identified by the surgical pathologist as "normal ovaries, adnexa, and uterus."
      The patient's karyotype was subsequently found to be 46,XX. CONCLUSION: The
      diagnosis of ambiguous genitalia in an elderly patient is uncommon. This dilemma
      poses additional ethical concerns for the physician, related to balancing the
      obligation to preserve patient autonomy with the obligation to protect patients
      from potential psychologic harm as a result of such an unusual diagnosis.

PMID- 15251667
TI  - Pituitary apoplexy after anticoagulation for unstable angina.
AB  - OBJECTIVE: To describe a patient with an undiagnosed pituitary macroadenoma, in
      whom pituitary apoplexy developed after heparin anticoagulation for treatment of
      unstable angina. METHODS: We chronicle the clinical course, treatment, and
      outcome in a 53-year-old woman with pituitary apoplexy. Potential risk factors
      are also discussed. RESULTS: In a patient with coronary artery disease and
      unstable angina, heparin anticoagulation therapy was initiated. Shortly
      thereafter, severe frontal headaches, nausea and vomiting, high fever, diplopia,
      and visual field deficits developed. A workup for infectious causes and analysis
      of cerebrospinal fluid were negative. Contrast-enhanced computed tomography of
      the head revealed a pituitary macroadenoma with a central area of hemorrhage, and
      pituitary apoplexy was diagnosed. Hydrocortisone sodium succinate was
      administered intravenously, and ultimately, transsphenoidal resection was
      performed. Postoperatively, diabetes insipidus developed and persisted.
      Neurologically, she had near-total blindness of the right eye and temporal
      hemianopia of the left eye. CONCLUSION: Although pituitary apoplexy is rare, its
      occurrence can be associated with certain risk factors, including
      anticoagulation. Clinicians should be aware of this serious condition so that
      timely diagnosis and treatment can provide the best chance of recovery.

PMID- 15251668
TI  - Glucocorticoid-induced muscle atrophy: mechanisms and therapeutic strategies.
AB  - OBJECTIVE: To analyze the mechanisms of action of glucocorticoids in causing
      muscle atrophy and to examine the therapeutic effect of testosterone as well as
      other treatment modalities in counteracting this adverse effect. METHODS: We
      reviewed selected publications to analyze the mechanisms of glucocorticoid
      induced muscle atrophy in animal models and in humans. The pathophysiologic
      features of glucocorticoid-induced hypogonadism and the possible relationship to
      the muscle atrophy in patients receiving glucocorticoids were assessed. The
      beneficial effects of testosterone on the muscles of hypogonadal and eugonadal
      men were also reviewed. Other measures such as exercise and glutamine and their
      possible therapeutic and preventive effects were examined in the context of
      hypercortisolemia. RESULTS: Glucocorticoids induce rapid muscle breakdown and
      proximal muscle atrophy. The mechanism of glucocorticoid-induced muscle atrophy
      relies on the degradation of the myosin heavy chain (catabolic effect), the most
      important contractile protein in muscle, associated with a decrease of its
      synthesis (antianabolic effect). One of the contributing factors in the
      development of muscle atrophy is hypogonadism that is induced by long-term
      glucocorticoid use. Androgen possesses anabolic and anticatabolic effects in
      vitro and in animal models. Androgens can be used safely to counteract the
      catabolic effects of cortisol. Other measures such as exercise, glutamine, and
      alanyl-glutamine are promising in animal models of glucocorticoid-induced muscle
      atrophy. CONCLUSION: This study suggests the possible efficacy of testosterone
      and glutamine on glucocorticoid-induced muscle atrophy. Testosterone and
      glutamine are natural biologic products with safe pharmacologic profiles, and
      their bioefficacy merits active research in humans.

PMID- 15251669
TI  - Socioeconomics of coding for endocrine services.
AB  - OBJECTIVE: To review the current coding systems for procedures and services as
      well as for diagnoses and to address special issues in endocrine disorders such
      as diabetes relative to reimbursement. METHODS: A method of coding for services
      to maximize reimbursement and minimize errors and denials of claims is discussed.
      Useful checklists and resources are also provided. RESULTS: Medicare policies
      have become increasingly complex, and continual changes in coverage of medical
      services and procedures can be confusing. Suggestions are presented for securing
      timely payment for claims, and thorough documentation is emphasized. "Bundling"
      of codes by payers, a common practice with new screening software systems, is
      explained. Strategies are described for negotiating contracts that specify prompt
      payment periods and include penalties for late payments. CONCLUSION: Awareness of
      current codes for health care services and diagnoses will facilitate the
      processing of claims and optimize reimbursements.

PMID- 15251670
TI  - Technetium-99m sestamibi scintigraphy and bone densitometry in primary
      hyperparathyroidism.
AB  - OBJECTIVE: To review our recent experience with technetium-99m sestamibi
      scintigraphy in identification and localization of parathyroid adenomas and to
      determine bone mineral loss associated with primary hyperparathyroidism. METHODS:
      Thirty-two double-phase technetium-99m sestamibi scans were obtained in 26
      patients (22 female and 4 male patients; age range, 14 to 78 years). Serum
      calcium and intact parathyroid hormone concentrations were measured before
      scintigraphy. Histopathologic correlation was obtained in all patients who
      underwent a surgical procedure. Seventeen patients underwent bone densitometry
      studies of the lumbar spine and hip with use of dual-energy x-ray absorptiometry.
      RESULTS: Of the 32 scans, 17 (53%) were suggestive of a parathyroid adenoma
      ("positive"). In these patients, the mean serum calcium concentration was 2.68
      mmol/L and the mean serum parathyroid hormone concentration was 669 pg/mL.
      Overall, one false-negative scan and one false-positive scan were encountered.
      The overall sensitivity for surgically proven detection and localization of
      parathyroid adenoma was 90%. The bone density measurements in patients with
      positive scans were substantially lower in the lumbar spine (mean T score, 2.9)
      and in the hip (mean T score, 2.1) in comparison with normal control subjects and
      significantly lower than in those with a negative scan (spine, P = 0.011; hip, P
      = 0.015). CONCLUSION: Double-phase technetium-99m sestamibi scintigraphy is
      highly sensitive and useful in detection and localization of parathyroid
      adenomas. Patients with primary hyperparathyroidism lose bone mineral from both
      cortical and cancellous bone sites.

PMID- 15251671
TI  - Effect of intensive insulin therapy on progression of overt nephropathy in
      patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: To assess the effects of chronic (long-term) intermittent intravenous
      insulin therapy (CIIIT) on the progression of overt nephropathy in patients with
      type 1 diabetes mellitus. METHODS: We undertook a retrospective longitudinal
      three-center study of 31 patients with type 1 diabetes mellitus and overt
      nephropathy, who were receiving intensive subcutaneous insulin therapy (four
      insulin injections daily) and weekly CIIIT. All study patients had follow-up
      consultations weekly for at least 12 months (mean duration, 37.0 +/- 4.6 months).
      Each patient had monthly hemoglobin A(1c) (by high-performance liquid
      chromatography) and semiannual creatinine clearance determinations. RESULTS: The
      hemoglobin A(1c) levels declined significantly from 8.6 +/- 0.6% to 7.6 +/- 0.3%
      (P = 0.0062) during the study period. The creatinine clearance remained
      essentially unchanged (from 46.1 +/- 3.0 mL/min per 1.73 m 2 at baseline to 46.0
      +/- 3.9 mL/min per 1.73 m 2 at the end of the observation period, with an average
      annualized slope increase of 3.39 +/- 1.5 mL/min per year--no significant
      difference). CONCLUSION: The addition of CIIIT to intensive subcutaneous insulin
      therapy in patients with type 1 diabetes mellitus seems to arrest or appreciably
      reduce the progression of overt diabetic nephropathy, as well as substantially
      improve their glycemic control.

PMID- 15251672
TI  - Effect of the new diagnostic criteria for diabetes in the Mexico City study.
AB  - OBJECTIVE: To assess the effect of the new American Diabetes Association (ADA)
      diagnostic criteria for diabetes in the Mexico City survey. METHODS: The data
      available from the Mexico City study were included. This cross-sectional survey
      was conducted from January 1991 to March 1992 and involved 805 adults (20 years
      of age or older; mean age, 41 years). Survey procedures and results were
      previously published. Of the residents with diabetes, 74.2% had a previous
      diagnosis, and 25.8% were diagnosed on the basis of fasting plasma glucose (FPG)
      levels obtained during the survey. For the current report, these data were
      reanalyzed on the basis of the new ADA diagnostic criteria. RESULTS: The
      prevalence of newly diagnosed diabetes with use of the old and the new criteria
      was 23.1% versus 32.3% in men (P = 0.31) and 27.5% versus 36.3% in women (P =
      0.32), respectively. The crude prevalence rate of diabetes increased from 8.7% to
      9.3% (P = 0.42), and the age-adjusted rate increased from 10.6% to 11.2% for
      women (P = 0.64) and from 6.0% to 6.5% for men (P = 0.49). The prevalence of
      impaired FPG was 4.8%. Those patients with impaired FPG or newly diagnosed
      diabetes with FPG levels between 126 and 140 mg/dL had a more atherogenic risk
      profile than did those with normal carbohydrate metabolism. CONCLUSION: On the
      basis of the 1990 population census in Mexico City, the new ADA criteria will add
      28,331 patients with diabetes (6.9%) to an already insufficient medical system.
      For those patients with impaired FPG or newly diagnosed diabetes on the basis of
      the new criteria, management should be focused on the control of the diverse and
      highly prevalent coronary risk factors.

PMID- 15251673
TI  - Effect of alendronate treatment on bone mineral density in male patients with
      osteoporosis.
AB  - OBJECTIVE: To assess the efficacy of alendronate therapy on bone mineral density
      (BMD) at the lumbar spine and hip in men with osteoporosis. METHODS: Medical
      records of male patients with osteoporosis, who had undergone follow-up in the
      Endocrinology Clinic at the National Naval Medical Center, were reviewed, and
      nine patients treated with alendronate for at least 1 year were identified.
      Patients were excluded from analysis if they had evidence of osteomalacia or if
      baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry
      (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD
      results at the lumbar spine and hip, before and after at least 10 months of
      alendronate treatment, were analyzed for significant differences. Patients were
      also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one
      patient received vitamin D (400 to 800 U/day). RESULTS: Lumbar spine BMD
      increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean
      absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted
      for the entire study group (N = 9), after a mean duration of treatment of 14 +/-
      1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002)
      with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per
      year with alendronate treatment (P = 0.013). The mean absolute gain in femoral
      neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after
      14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/-
      0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/-
      1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P =
      0.061) were not statistically significant. Two patients discontinued alendronate
      treatment after 1 year because of epigastric or retrosternal pain. CONCLUSION:
      Oral alendronate treatment, given in combination with calcium supplementation and
      physiologic doses of vitamin D, resulted in significant improvements in lumbar
      spine and femoral neck BMD after a 14-month period in this small group of men
      with osteoporosis. Although controlled, prospective trials involving larger
      numbers of male patients with fracture incidence data are needed before
      definitive conclusions can be made, alendronate treatment seems to be effective
      in improving BMD in men with osteoporosis, similar to its efficacy in women.

PMID- 15251674
TI  - Thyroglossal duct cyst: an infrequently considered diagnosis in pediatric
      patients with anterior neck masses.
AB  - OBJECTIVE: To describe a pediatric patient with an anterior neck mass and discuss
      the evaluation and treatment. METHODS: We present a case report and a discussion
      of the differential diagnosis of anterior cervical masses. The workup and therapy
      for an anterior neck mass, which was a thyroglossal duct cyst, are reviewed.
      RESULTS: A thyroglossal duct cyst in pediatric patients is an uncommon finding.
      For establishing a correct diagnosis, surgical confirmation is necessary.
      Identification is important because of the high incidence of misdiagnosis,
      recurrent infections, inadequate treatment, and possible neoplastic change.
      CONCLUSION: A thyroglossal duct cyst should be included in the differential
      diagnosis of an anterior neck mass. Recommended treatment consists of surgical
      removal of the cyst, the entire thyroglossal duct tract, and the central portion
      of the hyoid bone.

PMID- 15251675
TI  - Parenteral feeding in a patient with hypertriglyceridemia and increased liver
      enzyme levels.
AB  - OBJECTIVE: To discuss nutritional support in a patient with hypertriglyceridemia
      and liver dysfunction. METHODS: We describe the hospital course of a critically
      ill patient with hepatic dysfunction and hypertriglyceridemia who required
      nutritional support, and we provide an overview of lipid metabolism. RESULTS: A
      27-year-old man with hepatic dysfunction and hypertriglyceridemia, who had
      undergone kidney transplantation 4 months previously, was admitted to the
      intensive-care unit with upper gastrointestinal bleeding. He was unable to
      tolerate enteral feeding, and central parenteral nutrition was initiated.
      Calories from dextrose and fat were limited because of the presence of increased
      liver enzyme levels and hypertriglyceridemia. A modified regimen of parenteral
      nutrition was developed for the patient. The short-term reduction of total
      calories to 75% of the predicted need is safe. CONCLUSION: Nutritional support in
      patients with liver dysfunction and hypertriglyceridemia is complicated and may
      require temporary underfeeding because of the need to limit fat and dextrose
      intake.

PMID- 15251676
TI  - Hypercalcemia in a woman with hypoparathyroidism associated with increased
      parathyroid hormone-related protein during lactation.
AB  - OBJECTIVE: To report a case of postpartum hypercalcemia in a woman with
      hypoparathyroidism associated with increased serum concentrations of parathyroid
      hormone-related protein (PTHrP) during lactation. METHODS: The clinical and
      laboratory data for our patient and the related literature are reviewed. RESULTS:
      A 35-year-old woman with long-standing surgical hypoparathyroidism treated with
      dihydrotachysterol and calcium carbonate gave birth to a healthy boy at 40 weeks
      of gestation and began lactating normally. Two and a half weeks later,
      hypercalcemia developed in association with nausea, vomiting, and myalgias.
      Subsequently, an increased serum PTHrP concentration was noted. After saline
      diuresis and corticosteroid therapy to correct the hypercalcemia, a normal serum
      calcium level was maintained without vitamin D preparations or calcium
      supplements until the 12th postpartum week, when hypocalcemia reappeared. The
      serum PTHrP level was no longer increased, and treatment with calcitriol and
      calcium carbonate was resumed. Subsequent serum calcium concentrations have been
      normal. CONCLUSION: This case suggests that PTHrP stimulation of the parathyroid
      hormone-PTHrP receptor during lactation may compensate for the absence of
      parathyroid hormone in lactating women with hypoparathyroidism and that treatment
      with pharmacologic doses of vitamin D preparations during the postpartum period
      may result in hypercalcemia.

PMID- 15251677
TI  - Isolated hypogonadotropic hypogonadism in a man with a history of head trauma
      during childhood.
AB  - OBJECTIVE: To report a case of isolated hypogonadotropic hypogonadism as a
      delayed consequence of major head injury. METHODS: We present the relevant
      history, findings on physical examination, and results of laboratory evaluation,
      and supportive data from appropriate reports in the literature are reviewed.
      RESULTS: A 37-year-old man with progressive loss of libido, impotence, and
      gradual loss of facial and axillary hair had sustained severe trauma to the head
      (sufficient to cause blindness in one eye) in a fall from a tree at 7 years of
      age. Physical examination and laboratory investigations substantiated the
      presence of isolated hypogonadotropic hypogonadism. Other causes of
      hypogonadotropic hypogonadism, including Kallmann's syndrome, were excluded.
      CONCLUSION: Severe head injury should be considered in the differential diagnosis
      of isolated hypogonadotropic hypogonadism. Long-term follow-up and endocrine
      assessment may be important in patients who have sustained severe head injury.

PMID- 15251678
TI  - Combination therapy for type 2 diabetes.
AB  - OBJECTIVE: To discuss a rational approach to improvement of glycemic control in
      patients with type 2 diabetes mellitus with use of combination therapy. METHODS:
      We review the mechanisms of action and clinical applications for the various
      antidiabetic agents alone and in various combinations. Relevant studies in the
      literature are reviewed. RESULTS: Although diet and exercise remain the
      cornerstones of treatment, in most patients with type 2 diabetes, pharmacologic
      agents are needed to achieve optimal glycemic control and likely reduce the
      incidence of microvascular and possibly macrovascular complications as well.
      Sulfonylureas have long been the foundation of oral pharmacologic therapy and
      provide adequate glycemic control for most patients for 5 to 10 years or longer.
      In the past, when treatment with sulfonylureas was no longer effective, insulin
      therapy was inevitable. With the approval of several new pharmacologic agents for
      the treatment of type 2 diabetes, however, the addition of one or more orally
      administered agents to sulfonylurea therapy or use of other oral combination
      therapy is rapidly evolving as a means of optimizing glycemic control. In many
      patients, combination therapy can delay the need to add or switch to insulin, or
      it can enhance glycemic control in patients already receiving insulin. In
      selected patients treated solely with insulin, discontinuation of insulin
      treatment and reinitiation of oral therapy may even be possible. CONCLUSION:
      Currently, four classes of orally administered antidiabetic agents are available
      for use in patients with type 2 diabetes: insulin secretagogues, biguanides, a
      glucosidase inhibitors, and thiazolidinediones. By taking advantage of differing
      mechanisms of action, combination therapy is evolving as a means of optimizing
      glycemic control in patients in whom a single agent or insulin is inadequate.
      Combinations of orally administered agents can often delay the need for insulin
      or in combination with insulin aid in achieving glycemic goals. Continuing
      research will help optimize combination therapies even further.

PMID- 15251679
TI  - Atypical thyroiditis in Huelva, Spain.
AB  - OBJECTIVE: To report an epidemic of atypical thyroiditis that occurred in
      southwestern Europe during 1995. METHODS: We present the clinical, laboratory,
      morphologic, and histologic features of 672 cases of thyroiditis and describe the
      results of treatment. RESULTS: During 1995, atypical thyroiditis was diagnosed in
      672 of 725 patients with thyroid disorders encountered at our medical center in
      Huelva, Spain. Of these patients, 98% were women with normal ovarian function.
      The clinical findings were acute or subacute manifestation of diffuse nodular
      enlargement of the thyroid and spontaneous, severe pain on deglutition and
      palpation of the gland. Initial hematology and serum biochemistry studies, free
      triiodothyronine, free thyroxine, thyrotropin, and thyroid-stimulating
      immunoglobulins were in the normal range, but after the second week, the
      thyrotropin level began to increase. Thyroid antibodies (thyroglobulin and
      thyroid peroxidase) increased up to 300 times the high-normal level.
      Ultrasonography exhibited diffuse nodular enlargement of the thyroid gland, with
      irregular hypoechoic, normal, and hyperechoic zones. Fine-needle aspiration
      biopsy showed abundant lymphocytic infiltration. The best treatment results were
      obtained with the combination of levothyroxine and deflazacort. Because the
      epidemic appeared after a severe drought of 5-year duration (1991 to 1995) and
      affected women with normal ovarian function, our etiopathogenetic hypothesis was
      that an estrogen-like chemical substance polluted the area swamps. The high
      concentration of the pollutant was attributable to diminished water levels (8% of
      their capacity at the end of the drought period), and this situation may have
      affected the population through tap water used for human consumption. CONCLUSION:
      We describe an atypical autoimmune thyroiditis that affected primarily women of
      reproductive age, after a severe drought. The main features were a very painful,
      diffuse nodular enlargement of the thyroid gland, substantially increased thyroid
      antibodies, good response to levothyroxine and deflazacort combination treatment,
      and a benign evolution to chronic thyroiditis. Pollutants from various sources
      should be considered when atypical thyroiditis occurs in any community.

PMID- 15251680
TI  - C-Peptide utilization in clinical practice: effect on treatment and outcome of
      diabetes in a series of cases.
AB  - OBJECTIVE: To emphasize that measurement of a C-peptide level can be critical in
      the diagnosis and appropriate management of patients with diabetes mellitus.
      METHODS: We present a series of clinical cases in which glycemic control proved
      challenging, and we discuss the underlying pathophysiologic features of type 1
      versus type 2 diabetes. RESULTS: In a series of 12 illustrative cases, suboptimal
      control of blood glucose levels in patients with diabetes prompted further
      investigation. Assessment of C-peptide levels helped determine a precise
      diagnosis of type 1 or type 2 diabetes, information that was pivotal in choosing
      treatment options and improving the outcome. These examples show that the age of
      the patient at the time of diagnosis of diabetes does not necessarily indicate
      the type of diabetes that is present. CONCLUSION: Clinicians should be aware of
      the importance of establishing whether patients have type 1 or type 2 diabetes
      mellitus and the implications of that distinction on the effectiveness of
      therapeutic strategies.

PMID- 15251681
TI  - Compliance with guidelines for thyroid nodule evaluation.
AB  - OBJECTIVE: To determine whether guidelines recommended by the American
      Association of Clinical Endocrinologists (AACE) for assessment of a solitary
      thyroid nodule have been applied in clinical practice. METHODS: We
      retrospectively examined the pattern of testing in patients with solitary thyroid
      nodules at our institution during a 2-year period. We also attempted to determine
      whether consultation with an endocrinologist affected the workup. Patients who
      underwent a thyroid scan, ultrasonography, fine-needle aspiration (FNA) biopsy,
      or a thyroid surgical procedure for investigation of a solitary thyroid nodule
      between Jan. 1, 1996, and Dec. 31, 1997, were included in the study. Test results
      were reviewed for these patients. Patients were categorized into two groups,
      those with and those without a consultation with an endocrinologist. RESULTS:
      Inclusion criteria were met by 89 patients, 65% of whom had an FNA biopsy in
      their evaluation (the sole test in only 9%). A thyroid scan was done in 90% of
      patients, and an ultrasound study was done in 25%. Patients seen by an
      endocrinologist were more likely to undergo FNA biopsy than those who were not
      (82% versus 29%; P<0.001). Many patients who underwent assessment because of
      solitary nodules had normal findings on thyroid scans (21% of scans). CONCLUSION:
      The AACE guidelines for evaluation of thyroid nodules have not yet been fully
      implemented. Although a third of all study patients with a solitary thyroid
      nodule did not have an FNA biopsy, endocrine referral increased the rate of
      performance of this procedure. Thyroid scans seem to be overutilized; the high
      number with normal findings suggests that nuclear imaging studies are done to
      confirm physical findings. Early referral to an endocrinologist may be a more
      cost-effective workup of a possible thyroid nodule.

PMID- 15251682
TI  - Serum leptin concentration in patients infected with human immunodeficiency
      virus.
AB  - OBJECTIVE: To assess the potential effect of serum leptin levels in human
      immunodeficiency virus (HIV)-related wasting. METHODS: Morning serum leptin
      levels of 94 randomly chosen HIV-infected patients were measured and correlated
      with age, sex, weight, height, body mass index (BMI), routine blood chemistries
      (SMA 18), complete blood cell count, HIV viral load, and CD4/CD8 ratio. RESULTS:
      The mean serum leptin level was 7.0 +/- 6.9 ng/mL. Leptin levels were
      significantly higher in the 38 female patients than in the 56 male patients (10.0
      +/- 8.4 ng/mL versus 5.0 +/- 4.9 ng/mL; P<0.001). Leptin levels were positively
      correlated with BMI (r = 0.71; P<0.05). The correlation of leptin levels with BMI
      was improved when the results were analyzed stratified by the sex of the patients
      (r = 0.74 for female patients; r = 0.81 for male patients). CONCLUSION: This
      study showed that the serum leptin levels in HIV-infected patients with BMI
      between 18 and 25 kg/m 2 were comparable to leptin levels in lean, healthy
      subjects. Leptin distribution was positively correlated with BMI, as expected.
      These data do not support the hypothesis for a major role of serum leptin in HIV
      related wasting.

PMID- 15251683
TI  - Nelson's syndrome due to an intracavernous corticotropin-secreting adenoma.
AB  - OBJECTIVE: To report the first case of Nelson's syndrome due to an ectopic
      intracranial corticotropin-secreting tumor arising entirely within the cavernous
      sinus. METHODS: We present a case report of Nelson's syndrome with clinical,
      laboratory, and radiologic features throughout a 25-year period. RESULTS: A 54
      year-old woman had been treated for Cushing's disease with bilateral
      adrenalectomy in 1971. Subsequently, Nelson's syndrome developed, and she had
      severe generalized hyperpigmentation and substantially increased plasma
      corticotropin levels. In 1976, she underwent a transsphenoidal hypophysectomy.
      Postoperatively, despite the development of panhypopituitarism and diabetes
      insipidus, she remained hyperpigmented and had persistently increased plasma
      corticotropin levels. Throughout the years, efforts to identify the site of the
      corticotropin-secreting tumor were unsuccessful until 1988, when magnetic
      resonance imaging revealed a mass in the right cavernous sinus; subsequently,
      petrosal sinus cannulation corroborated the intracavernous source of excess
      corticotropin. Cobalt-60 gamma knife radiotherapy in 1992 was followed by a
      clinical and hormonal response 4 1/2 years later. CONCLUSION: This report
      describes only the second reported case of an intracranial corticotropin
      secreting tumor arising entirely within the cavernous sinus and the first such
      case associated with Nelson's syndrome. Although rare, the possibility of an
      ectopic intracranial or extracranial pituitary adenoma should be considered in
      patients with pituitary hypersecretion without clear-cut intrasellar
      abnormalities or those with no response to surgical resection of the pituitary
      gland.

PMID- 15251684
TI  - Mediastinal parathyroid carcinoma.
AB  - OBJECTIVE: To describe a patient with a mediastinal parathyroid carcinoma and
      hypercalcemia as well as to compare the features of parathyroid carcinoma with
      those of hypercalcemia due to other causes of primary hyperparathyroidism.
      METHODS: We present a case report and discuss the diagnosis and management of
      this rare tumor. RESULTS: In a 44-year-old man, severe hypercalcemia and normal
      findings on neck exploration led to referral and ultimate detection of an
      anterior mediastinal mass. Surgical resection and pathologic examination of the
      mass revealed a cystic parathyroid carcinoma. Subsequently, normalization of
      serum calcium and parathyroid hormone levels ensued. CONCLUSION: Parathyroid
      carcinoma as an alternative to the diagnosis of primary hyperparathyroidism
      should be considered in patients with dramatically increased serum calcium and
      parathyroid hormone levels at the time of initial examination. The mainstay of
      therapy for parathyroid carcinoma is complete surgical resection. Accurate
      preoperative localization of parathyroid carcinoma is helpful, especially in
      instances of reoperation or hypercalcemic crisis.

PMID- 15251685
TI  - Serious hypoglycemia associated with misuse of repaglinide.
AB  - OBJECTIVE: To report the first case of a serious hypoglycemic episode associated
      with the misuse of repaglinide. METHODS: The history, clinical findings,
      laboratory features, and clinical course of this case are described. RESULTS: In
      a 48-year-old man with autoimmune hepatitis, diabetes developed in association
      with corticosteroid therapy. Postprandial plasma glucose levels remained in the
      range of 150 to 200 mg/dL after a 6-week trial of diet-alone therapy, and
      treatment was begun with repaglinide, 0.5 mg before each meal. On the 11th day of
      therapy, the patient had a severe episode of hypoglycemia (plasma glucose level
      of 33 mg/dL) and seizures during the night, after forgetting his dose of
      repaglinide before the evening meal and subsequently taking the medication 3
      hours after that meal. CONCLUSION: Serious hypoglycemia is always a potential
      consequence of agents that stimulate endogenous release of insulin. In this case
      report, serious hypoglycemia occurred in a patient at higher risk by virtue of
      hepatic insufficiency and was clearly associated with the misuse (late
      postprandial administration) of repaglinide. Continued emphasis on the need to
      administer repaglinide before meals (and to omit the drug if a meal has been
      missed or the dose has not been taken preprandially) is indicated if hypoglycemic
      episodes are to be avoided.

PMID- 15251686
TI  - Tumor-grade hyperprolactinemia induced by multiple medications in the setting of
      renal failure.
AB  - OBJECTIVE: To describe a patient with galactorrhea and severe hyperprolactinemia
      in whom workup revealed a nontumoral mechanism. METHODS: We present the medical
      history of a woman with long-standing diabetes in whom bilateral galactorrhea and
      hyperprolactinemia developed. In addition, the details of her clinical course and
      management are reviewed. RESULTS: A 33-year-old woman with diabetes, end-stage
      renal disease, and gastroparesis was admitted to the hospital because of
      intractable nausea and vomiting. Several months before admission, she had been
      noted to have galactorrhea and irregular menses. Routine medications included
      captopril, verapamil, furosemide, prochlorperazine, metoclopramide, cisapride,
      and Ortho-Novum. Laboratory evaluation showed normal thyroid function, increased
      serum prolactin levels (up to 1,197 ng/mL), and normal findings on magnetic
      resonance imaging of the pituitary. Electrophoresis of the patient's serum on a
      protein A Sepharose column showed no evidence of macro-prolactinemia. Orally
      administered medications were discontinued, and the patient was given total
      parenteral nutrition. These measures resulted in a decrease of 300 ng/mL in serum
      prolactin levels in 4 days. The prolactin levels eventually normalized after
      withdrawal of verapamil, prochlorperazine, and metoclopramide. CONCLUSION: A
      modest increase in serum prolactin level often can be produced by a variety of
      medications, but gross hyperprolactinemia of 200 ng/mL or higher usually raises
      suspicion of an underlying prolactin-secreting tumor. This case report
      demonstrates that conventional limits for nontumoral hyperprolactinemia can be
      exceeded by concurrent exposure to multiple lactotropic medications in the
      setting of renal failure.

PMID- 15251687
TI  - Hypopituitarism in two brothers born by breech delivery.
AB  - OBJECTIVE: To describe two brothers with hypopituitarism who had been born by
      breech delivery and to discuss whether this condition corresponds to a familial
      form or to a pituitary stalk section as a result of the breech delivery. METHODS:
      We present the clinical, biochemical, and magnetic resonance imaging (MRI)
      characteristics of two Mexican brothers, 19 and 21 years old, with
      hypopituitarism and a history of breech delivery. RESULTS: Physical examination
      of both patients showed short stature with normal body proportions, an obviously
      younger appearance than that expected for their chronologic age, high-pitched
      voice, irregularly positioned teeth, no axillary or pubic hair, and prepubertal
      genitalia. Biochemical testing showed low thyroxine and free thyroxine values
      with inadequate or normal thyrotropin, low basal testosterone, and mildly
      increased serum prolactin levels. Stimulation tests showed a normal and a delayed
      thyrotropin response to thyrotropin-releasing hormone, subnormal serum cortisol,
      considerably blunted growth hormone (GH) response to insulin-induced
      hypoglycemia, and absence of GH response to GH-releasing hormone in both cases.
      MRI showed an ectopic neuropituitary gland. In case 1, a caudal portion of a very
      thin pituitary stalk was observed, suggesting the preservation of a vascular
      component of the stalk. Because both parents of these brothers shared the major
      histocompatibility complex haplotype HLA-A*2301, B*3501, DRB1*0407, DQA1*03,
      DQB1*0201, consanguinity was suggested. CONCLUSION: The phenotype of these
      patients differs from that described in families with POU1F1 (Pit-1) and PROP1
      mutations. These cases are most likely related to an autosomal recessive gene
      mutation that warrants further research. To our knowledge, this is the first
      report of hypopituitarism in two brothers born by breech delivery.

PMID- 15251688
TI  - Thyroid microcarcinoma: prevalence, prognosis, and management.
AB  - OBJECTIVE: To review the usual course of thyroid microcarcinoma (TMC) and the
      associated prognosis and treatment of affected patients. METHODS: We discuss
      predisposing factors in the formation of TMC and the modulation of its behavior,
      diagnostic evaluation, and management options. RESULTS: TMC, generally defined as
      a well-differentiated thyroid cancer less than or equal to 15 mm in diameter, has
      an estimated prevalence (based on autopsy studies) of about 5 to 10%. Studies,
      however, have shown that most of these cancers are smaller than 5 mm in diameter.
      The high prevalence of TMC in the general population contrasts with the rarity of
      thyroid cancers of greater size, which constitute less than 1% of malignant
      neoplasms in the United States. The frequent detection of TMC as a result of
      routine imaging of the neck for unrelated reasons and as a incidental finding in
      surgical specimens has raised a question about whether the management of TMC
      should differ from that for thyroid cancer of appreciable size. The uncertainty
      about optimal management of TMC is attributable to the small number of long-term
      follow-up studies as well as the common observation that patients usually have an
      excellent prognosis. Although in most patients harboring a TMC the cancer remains
      quiescent and never becomes clinically significant, in some cases TMC can
      demonstrate an aggressive course. Several variables, such as older age,
      multifocality, bilateral disease, and extrathyroidal spread at initial
      assessment, may have some adverse prognostic significance. After a partial
      surgical removal of the thyroid gland for TMC, the recurrence rate may be as high
      as 11%. Therefore, a treatment dilemma is caused by the low propensity of TMC for
      progression to clinically significant disease, yet the potential for recurrence
      and aggressive behavior in some cases. CONCLUSION: In general, surgical resection
      of TMC is based on results of fine-needle aspiration biopsy and the rate of
      growth of the nodule. Aggressive management seems indicated in high-risk
      patients, particularly older patients, those with a history of radiation
      exposure, and those with multifocal disease, bilateral disease, or lymph node
      involvement.

PMID- 15251689
TI  - Inhibited hypothalamic-pituitary-thyroid axis in type I pseudohypoparathyroidism.
AB  - OBJECTIVE: To assess the hypothalamic-pituitary-thyroid axis in two patients with
      the diagnosis of type I pseudohypoparathyroidism established previously by
      characteristic clinical features and laboratory findings, including low serum
      Ca++, high parathyroid hormone concentration, and subnormal urinary cyclic
      adenosine monophosphate (cAMP) responses to exogenous administration of
      parathyroid hormone. METHODS: We determined serum thyroxine, triiodothyronine
      (T(3)), T(3) resin uptake, and 24-hour thyroidal uptake of 123 I before and after
      subcutaneous administration of thyroid-stimulating hormone (TSH), 10 U daily for
      3 days. Serum TSH levels were determined before and again at 15, 30, 45, and 60
      minutes after intravenous administration of thyrotropin-releasing hormone (TRH)
      (400 microg) after an overnight fast. Values noted in the two patients with type
      I pseudohypoparathyroidism were compared with those obtained in 10 normal
      volunteer control subjects. RESULTS: Serum thyroxine (T(4)), triiodothyronine
      (T(3)), T(3) resin uptake, and 24-hour 123 I uptake values for both patients with
      type I pseudohypoparathyroidism were within the normal ranges (5.5 to 11.5
      microg/dL for T(4), 90 to 190 ng/dL for T(3), 35 to 45% for T(3) resin uptake,
      and 10 to 35% for 24-hour 123I uptake). Their responses to administration of TSH,
      however, were all significantly lower in comparison with the mean values for the
      10 healthy control subjects. Basal TSH was higher in both patients with type I
      pseudohypoparathyroidism than in normal subjects, but TSH responses after
      administration of TRH, although not significantly different from normal, were
      blunted in relationship to the basal concentrations, as expressed as a percentage
      increase in TSH as well as a cumulative TSH response. CONCLUSION: The responses
      of pituitary thyrotrophs to TRH and the thyroid gland to TSH were both
      considerably inhibited in the patients with type I pseudohypoparathyroidism in
      comparison with normal control subjects. This finding may be yet another evidence
      of the lack of adequate generation of cAMP, an important second messenger needed
      for normal functioning of most polypeptide hormones, including TRH and TSH, in
      this syndrome.

PMID- 15251690
TI  - Hospital length of stay on a diabetes cluster unit.
AB  - OBJECTIVE: To determine whether the length of hospital stay for patients with
      either a primary or a secondary diagnosis of diabetes mellitus can be reduced by
      use of a diabetes cluster unit. METHODS: For a period of 12 months, we compared
      the length of hospital stay for 462 patients with diabetes who were admitted to a
      diabetes cluster unit and for 1,855 patients with diabetes who were admitted to
      the other medical and surgical units during the same period. Statistical analysis
      was done by comparing the calculated average length of stay for patients with
      primary and secondary diagnoses of diabetes admitted to both types of hospital
      accommodations and comparing these values with the expected lengths of hospital
      stay based on the New York Group Standard. RESULTS: The mean length of hospital
      stay for patients who were admitted to the diabetes unit for a primary diagnosis
      of diabetes was 5.8 days shorter than for those admitted to regular medical and
      surgical units (7.6 days or 1% below the expected duration versus 13.4 days or
      70% longer than the expected duration, respectively; P<0.0002). For a secondary
      diagnosis of diabetes, patients in the diabetes unit had an average length of
      stay of 15.5 days (35% longer than the expected duration) in comparison with 17
      days (45% longer than expected) for patients on the other medical and surgical
      units (no significant difference). CONCLUSION: For hospitalization of patients
      with diabetes, geographic clustering seems to reduce the length of stay for
      patients with a primary diagnosis of diabetes mellitus.

PMID- 15251691
TI  - Direct extension of malignant lesions to the thyroid gland from adjacent organs:
      report of 17 cases.
AB  - OBJECTIVE: To characterize malignant tumors with direct extension to the thyroid
      gland from adjacent organs. METHODS: We retrospectively studied 17 patients with
      direct extension of malignant tumor to the thyroid from primary lesions in the
      head and neck who had been examined at Mayo Clinic Rochester between 1985 and
      1994. The origin of the primary tumor was identified in all cases. Thyroid
      involvement was confirmed histologically. Data were analyzed for the frequency
      and types of malignant lesions, the clinical course, and the follow-up after
      thyroid involvement. RESULTS: All 17 study patients had a diagnosis of a primary
      malignant tumor before detection of thyroid involvement. Of the 17 patients, 12
      had squamous cell carcinoma (SCC) of the larynx, 2 had SCC of the tongue base, 2
      had SCC of the proximal and the cervical esophagus, respectively, and 1 had
      synovial cell sarcoma of the proximal esophagus. The time between diagnosis of
      the primary tumor and detection of thyroid invasion in the patients with SCC of
      the larynx or tongue base ranged from 1 to 196 months (mean, 38). Only 1 of these
      14 patients had thyroid gland involvement clinically evident before surgical
      exploration. Thyroid invasion was diagnosed after surgical intervention. All
      three patients with esophageal malignant tumors had thyroid involvement
      clinically. CONCLUSION: SCC of the larynx, tongue base, or proximal esophagus may
      invade the thyroid gland directly. SCC of the larynx may have the greatest
      tendency to extend to the thyroid. In patients with SCC, extension of the primary
      malignant tumor to the thyroid gland should be considered despite lack of
      clinical evidence.

PMID- 15251692
TI  - Triiodothyronine antibodies in patients with goiter.
AB  - OBJECTIVE: To investigate the prevalence of triiodothyronine (T(3)) antibodies in
      patients with goiter, the influence of these antibodies on the results of thyroid
      hormone measurements, and the potential relationship between T(3) antibodies and
      thyroid autoantibodies. METHODS: We undertook a study of 100 healthy control
      subjects (80 female and 20 male subjects) who had no clinical or biochemical
      evidence of thyroid disease and 100 patients (81 female and 19 male patients)
      with goiter. Serum concentrations of total T(3), total thyroxine, free T(3), and
      free thyroxine were measured by radioimmunoassay kits with a coated tube method.
      An immunoprecipitation method was used to detect anti-triiodothyronine auto
      antibodies. RESULTS: Patients with a T(3) antibody binding ratio +3 standard
      deviations (SD) above the mean for the normal control group were considered to
      have T(3) antibodies. Normal control group binding was 2.4 +/- 1.3%. On the basis
      of +3 SD, seven patients had T(3) antibodies. The mean serum total T(3) level was
      1.61 +/- 0.1 nmol/L in patients with binding ratios above +3 SD, whereas the mean
      serum total T(3) level was 2.23 +/- 0.3 nmol/L in patients without T(3)
      antibodies. Thus, patients with a binding ratio above +3 SD had a significant
      decrement in total T(3) levels. No correlation was found between the presence of
      T(3) antibody and antimicrosomal and antithyroglobulin antibodies. CONCLUSION:
      When serum thyroid hormone concentrations are measured with a coated tube
      radioimmunoassay method, antibodies can result in low T(3) concentrations. T(3)
      antibodies should be suspected whenever a discordance is noted between the
      measured thyroid hormone concentrations and the clinical status.

PMID- 15251693
TI  - Successful therapy for a mixed thyrotropin-and prolactin-secreting pituitary
      macroadenoma with cabergoline.
AB  - OBJECTIVE: To describe the first case of a mixed thyrotropin (TSH)- and prolactin
      secreting pituitary macroadenoma that responded to therapy with cabergoline.
      METHODS: We present a case report with clinical, laboratory, and radiologic
      details. RESULTS: An 84-year-old woman with central hyperthyroidism due to a
      mixed TSH- and prolactin-secreting pituitary macroadenoma was successfully
      treated with orally administered cabergoline, 0.25 mg twice per week. Serial
      assays of thyroid and pituitary hormones were done, and magnetic resonance
      imaging of the pituitary was performed before and 16 weeks after initiation of
      cabergoline therapy. The patient had complete resolution of the increased
      pituitary hormone indices within 6 weeks after implementation of therapy, and
      these results were sustained for more than 16 weeks. A magnetic resonance imaging
      scan showed no change in tumor size at 16 weeks of therapy. CONCLUSION: When
      medical treatment of TSH-secreting tumors is considered, choices of efficacious
      drugs are limited. To our knowledge, this report describes the first case of a
      long-acting dopamine agonist used successfully to control hypersecretion of a
      mixed TSH- and prolactin-secreting macroadenoma. Oral administration of
      cabergoline twice a week was effective, convenient, and well tolerated. Further
      evaluation of cabergoline, when indicated as medical therapy for TSH-secreting
      tumors, is warranted.

PMID- 15251694
TI  - A spurious markedly increased serum estradiol level due to an IgA lambda.
AB  - OBJECTIVE: To alert physicians about the potential for erroneous laboratory
      determinations of hormone levels and emphasize the need to assess the overall
      clinical situation as well. METHODS: We present a case report of a woman with a
      dramatically increased serum estradiol (E(2)) level on radioimmunoassay and
      review the studies that led to the conclusion that this laboratory finding did
      not reflect her true estrogen status. RESULTS: In a 41-year-old woman, an
      unnecessary surgical procedure was performed because of a falsely increased serum
      E(2) level and a unilateral ovarian mass. The markedly increased serum E(2)
      measured by radioimmunoassay was found to be attributable to an IgA lambda that
      bound to the 125 I-labeled tracer of the assay. CONCLUSION: When repeatedly
      abnormal hormone levels and the clinical picture seem discrepant, use of a
      different assay method should be considered.

PMID- 15251695
TI  - Cushing's syndrome in a patient with a corticotropin-releasing hormone-producing
      pheochromocytoma.
AB  - OBJECTIVE: To present the first case of Cushing's syndrome attributable solely to
      ectopic production of corticotropin-releasing hormone by a pheochromocytoma.
      METHODS: We summarize the clinical features and results of laboratory
      investigations in a patient with symptoms characteristic of Cushing's syndrome.
      RESULTS: Although Cushing's syndrome is usually caused by ectopic production of
      adrenocorticotropic hormone (ACTH), our current patient had clinical and
      biochemical evidence of hypercortisolism in conjunction with "normal" ACTH levels
      and nonsuppressible serum and urinary cortisol levels on low-dose and high-dose
      dexamethasone suppression testing. An abdominal computed tomographic scan
      revealed a 7.7-cm mass in the left adrenal gland. Light microscopic examination
      and immunohistochemical staining showed a pheochromocytoma with mild cortical
      hyperplasia. Immunostaining was positive for corticotropin-releasing hormone but
      negative for ACTH. CONCLUSION: To our knowledge, this is the first case of
      Cushing's syndrome in a patient with pheochromocytoma caused only by ectopic
      secretion of corticotropin-releasing hormone without accompanying secretion of
      ACTH.

PMID- 15251696
TI  - Testicular pathologic changes and the pituitary-testicular axis during human
      immunodeficiency virus infection.
AB  - OBJECTIVE: To chronicle pituitary-testicular axis dysfunction and its
      clinicopathologic features in homosexual men. METHODS: Between 1984 and 1992, 84
      homosexual men underwent longitudinal follow-up for 4 years. At entry into the
      study, 28 were seronegative and 56 were seropositive for human immunodeficiency
      virus (HIV). Although 40 subjects remained asymptomatic (nonprogressors), 16 had
      progression to acquired immunodeficiency syndrome (AIDS). Of those 16 patients
      with progression, 8 had AIDS within 2 years (early progressors) and 8
      demonstrated AIDS within 4 years after enrollment (late progressors), and all
      died. The testes of five patients were examined at autopsy. The control group had
      similar follow-up. Luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      testosterone, and bioavailable testosterone (bio-T) were measured in stored sera
      collected at 2-year intervals. The last hormonal measurement was between 3 and 24
      months before autopsy. Comparison was made between autopsied and nonautopsied
      patients with AIDS as well as between HIV nonprogressors and control seronegative
      men. The correlation between pathologic findings and hormonal status was examined
      by regression analysis. RESULTS: At baseline, testosterone, bio-T, LH, and FSH
      were not significantly different among all patients and subjects. During the
      study period, testosterone, bio-T, and serum gonadotropin levels remained
      unchanged in the seronegative homosexual men. In nonprogressors, serum FSH and LH
      concentrations remained unchanged, whereas testosterone and bio-T levels
      decreased significantly during this 4-year period. After progression to AIDS (in
      both groups of progressors), the serum FSH and LH levels were higher and the
      serum testosterone and bio-T were lower in comparison with values in the
      seronegative men. In late progressors to AIDS, FSH and LH increased, whereas
      serum testosterone and bio-T decreased significantly from baseline. All five
      patients with AIDS on whom autopsy was done had boundary wall thickening of the
      seminiferous tubules and decreased spermatogenesis. No significant differences
      were found in serum testosterone, bio-T, and LH between those in whom autopsy was
      or was not done; however, FSH was significantly higher in the autopsied cases.
      The serum testosterone and bio-T levels were negatively correlated with the
      interstitial inflammation. A significant correlation was also observed between
      change of bio-T and weight loss. CONCLUSION: We conclude that dysfunction of the
      pituitary-gonadal axis is common in HIV-infected men. All patients in whom
      autopsy was done because of AIDS-related diseases had been hypogonadal 3 to 24
      months before death. Decreased spermatogenesis, subacute interstitial
      inflammation, or both were seen at autopsy of patients with AIDS. Pathologic
      damage to the testes during AIDS was associated with decreased testosterone and
      bio-T as well as increased serum gonadotropin levels. In a substantial proportion
      of men with progression to AIDS, compensated hypogonadism (normal serum
      testosterone and increased serum LH levels) preceded the development of low serum
      testosterone level.

PMID- 15251697
TI  - Expression of thyrotropin-releasing hormone messenger RNA in human pituitary
      adenomas with follicle-stimulating hormone immunoreactivity.
AB  - OBJECTIVE: To assess the correlation between thyrotropin-releasing hormone (TRH)
      messenger RNA (mRNA) and the immunoreactive type of human pituitary adenomas.
      METHODS: Twenty-eight patients (14 to 73 years old) who had pituitary adenomas
      (18 nonfunctioning adenomas, 8 growth hormone-secreting adenomas, and 2
      prolactinomas) underwent surgical treatment. Pituitaries removed at autopsy from
      four patients without evidence of pituitary disease were used as controls.
      Fragments of pituitary adenomas were processed for TRH mRNA by in situ
      hybridization (radioactive and nonradioactive) and for TRH peptide and anterior
      pituitary hormones (b-thyrotropin, b-follicle-stimulating hormone [FSH],
      bluteinizing hormone [LH], prolactin, and growth hormone) by immunohistochemistry
      with use of the avidinbiotin technique. Quantitative immunohistochemical studies
      were performed by using image analysis software. The signal was considered
      positive when more than 5% of the cells were stained. RESULTS: Cells expressing
      TRH mRNA were detected in 22 of 28 pituitary adenomas--15 of 18 nonfunctioning
      pituitary adenomas, 5 of 8 growth hormone-secreting adenomas, and both
      prolactinomas. TRH peptide was revealed in only 10 adenomas, all expressing TRH
      mRNA as well. All but one nonfunctioning adenoma expressing TRH mRNA in more than
      5% of the cells were b-FSH immunoreactive (15 of 16 cases; P<0.005, c 2 test),
      whereas only 6 of 16 nonfunctioning adenomas exhibited both b-thyrotropin and TRH
      mRNA and only 5 of 16 were positive for both b-LH and TRH mRNA. CONCLUSION: These
      results confirm previous data demonstrating the presence of TRH mRNA and TRH
      peptide in human pituitary tumor cells. We further showed that the presence of
      TRH mRNA is significantly correlated with FSH immunoreactive gonadotropinomas.
      The release of FSH after an intravenous TRH test only in gonadotropinomas,
      together with local production of TRH, suggests a role for TRH in pathogenesis.

PMID- 15251698
TI  - Echocardiographic assessment of patients receiving long-term treatment with
      anorexiant medications.
AB  - OBJECTIVE: To describe the prevalence and evaluate the risk of echocardiogram
      determined valvulopathy in patients who received fenfluramine and phentermine in
      an effort to lose weight, in comparison with normal control subjects. METHODS: A
      historical cohort study was conducted in a clinical obesity-management practice.
      A total of 164 patients (88% women) who were treated with fenfluramine
      phentermine for weight loss had echocardiographic evaluations. A subsample was
      cross-validated. RESULTS: The prevalence of mild or greater aortic regurgitation
      was 18.3%, and the prevalence of moderate or greater mitral regurgitation was
      3.7%. The prevalences of mild or greater tricuspid and pulmonary valve
      regurgitation, valve thickening, and pulmonary hypertension were 23.2%, 5.5%,
      10.4%, and 6.7%, respectively. No significant increases in risk were found for
      moderate or greater regurgitation of any valve. Patients had at least a 3-fold
      risk for mild or greater aortic regurgitation (standardized morbidity ratio [SMR]
      = 3.03; 95% confidence interval [CI] = 2.05 to 4.33) and a 2-fold risk for
      tricuspid regurgitation (SMR = 2.24; 95% CI = 1.58 to 3.06) in comparison with
      normal healthy adults. Age and duration of drug therapy predicted increased risk
      for aortic regurgitation. Four patients who had moderate or greater aortic
      regurgitation had taken the fenfluramine-phentermine combination continuously for
      454, 615, 645, and 984 days. CONCLUSION: Use of serotonergic anorexiant
      medications may increase risk for mild or greater aortic and tricuspid
      regurgitation, although selection bias and obesity as causes of the association
      cannot be ruled out. Age and duration of drug therapy were predictors of aortic
      valvulopathy. Population-based studies are needed to confirm these preliminary
      findings.

PMID- 15251699
TI  - Pancreas and islet transplants for patients with diabetes: taking positions and
      making decisions.
AB  - OBJECTIVE: To help endocrinologists develop a position and then make decisions
      about the applicability of pancreas and islet transplantations for treatment of
      patients with diabetes. METHODS: An overview is provided of peer-reviewed
      literature reporting clinical outcomes of pancreas and islet transplantations,
      emphasizing rates of success, effect on metabolic regulation and secondary
      complications, and changes in the quality of life. RESULTS: Pancreas
      transplantation-related patient survival rates correspond generally to survival
      rates of similar patients who have not undergone transplantation, and organ
      survival rates are consistent with rates of other commonly transplanted organs.
      Beneficial effects include normalization of glycemia; restoration of glucagon,
      epinephrine, and symptom responses to hypoglycemia; stabilization of renal and
      neural complications; and improvement in the quality of life. Autoislet
      transplantation is commonly successful in preventing diabetes attributable to
      pancreatectomy for chronic pancreatitis. The success rates associated with
      alloislet transplantation remain low. CONCLUSION: Pancreas transplantation is a
      therapeutic, not an experimental, option that should be considered when patients
      with diabetes are candidates for kidney transplantation or when they are
      metabolically unstable despite optimal medical management. Autoislet
      transplantation is a therapeutic option that should be seriously considered for
      patients without diabetes destined to undergo pancreatectomy for chronic
      pancreatitis. Alloislet transplantation remains an experimental procedure for
      treatment of diabetes.

PMID- 15251700
TI  - Severe hypertriglyceridemia and acute pancreatitis during pregnancy: treatment
      with gemfibrozil.
AB  - OBJECTIVE: To describe the effect of gemfibrozil therapy during pregnancy in a
      woman with severe hypertriglyceridemia. METHODS: We present a case report, with
      details of lipid levels throughout several attempted pregnancies, and discuss
      other similar published studies. RESULTS: In a 22-year-old woman, severe acute
      pancreatitis due to hypertriglyceridemia developed during her first pregnancy.
      After a prolonged hospital course, the outcome was fetal demise. The patient was
      subsequently treated with gemfibrozil, which controlled the hypertriglyceridemia.
      A second pregnancy ended with a therapeutic abortion at 1 month because of the
      possible risk of pancreatitis. Gemfibrozil therapy was instituted but
      subsequently discontinued when she was discovered to be pregnant again, at
      approximately 10 weeks of gestation; the potential risks involved with the use of
      this drug during pregnancy were unknown. Because of the patient's strong desire
      to maintain the pregnancy, gemfibrozil treatment was resumed 1 week later in
      order to help prevent recurrent pancreatitis. The patient ultimately delivered a
      fullterm healthy boy, and she had no recurrence of pancreatitis or other
      complications. CONCLUSION: In selected patients at high risk for pancreatitis,
      the potential risk of gemfibrozil use during pregnancy may be offset by its
      benefits in the management of severe hypertriglyceridemia.

PMID- 15251701
TI  - Hypoglycemia attributable to insulin-like growth factor-II prohormone-producing
      metastatic leiomyosarcoma.
AB  - OBJECTIVE: To review the causes of nonpancreatic tumor-associated hypoglycemia
      and report the first case of hypoglycemia attributable to a leiomyosarcoma, which
      did not cause hypoglycemia in its primary site but only after metastasizing.
      METHODS: A case report is presented of a 62-year-old man with a gastric
      leiomyosarcoma diagnosed and surgically treated 8 years previously, who was found
      to have 14 large, rounded masses in his liver and a blood glucose level of 19
      mg/dL. Biopsy of the largest mass revealed a leiomyosarcoma. RESULTS: Evaluation
      of the cause of the hypoglycemia revealed that circulating insulin, connecting
      peptide, proinsulin, insulin-like growth factor-I (somatomedin C), and insulin
      like growth factor-II levels were below normal, whereas the insulin-like growth
      factor-II prohormone concentration was increased twofold. Basal and corticotropin
      stimulated serum cortisol values were normal. CONCLUSION: This is the first case
      report of hypoglycemia occurring only after metastasis of a leiomyosarcoma. A
      possible causal relationship between the hypoglycemia and the increased
      circulating insulin-like growth factor-II prohormone is suggested, and
      alternative explanations and treatment are discussed.

PMID- 15251702
TI  - Sarcoidosis after surgically induced remission of Cushing's disease.
AB  - OBJECTIVE: To describe a rare case of sarcoidosis diagnosed after surgical
      resection of an adenoma in a patient with Cushing's disease. METHODS: We present
      a case report and discuss the only other similar case identified from the
      published medical literature. RESULTS: In a 33-year-old woman with symptoms of
      cortisol excess (including progressive weight gain, proximal muscle weakness,
      ecchymoses, and amenorrhea), laboratory studies showed serum cortisol values
      consistent with Cushing's syndrome. After inferior petrosal sinus sampling, the
      patient underwent surgical resection of an adenoma in the right aspect of the
      anterior pituitary gland. Maintenance corticosteroid therapy was implemented, and
      the signs and symptoms of Cushing's disease began to resolve. Five months
      postoperatively, multiple erythematous lesions developed on the patient's arms
      and legs. Skin biopsy specimens demonstrated noncaseating granulomas, and
      sarcoidosis was diagnosed. Two months later, the lesions resolved spontaneously
      without therapy other than continued corticosteroid replacement. CONCLUSION:
      Physicians should be aware that unusual postoperative symptoms in a patient who
      has undergone successful treatment of Cushing's syndrome may be attributable to
      the emergence of another corticosteroid-responsive disease such as sarcoidosis.

PMID- 15251703
TI  - Systemic calciphylaxis in a patient with end-stage renal disease and a normal
      parathyroid hormone level taking erythropoietin intramuscularly.
AB  - OBJECTIVE: To describe a patient with systemic calciphylaxis. METHODS: We present
      a case of a 26-year-old woman with end-stage renal disease taking intramuscular
      injections of erythropoietin in whom systemic calciphylaxis subsequently
      developed. Both clinical and laboratory findings are reviewed. RESULTS: In a 26
      year-old woman with end-stage renal disease who was taking erythropoietin
      intramuscularly, multiple, superficial ulcerative lesions developed on both lower
      extremities. Despite aggressive treatment, new lesions subsequently developed.
      Laboratory values showed an increased calcium-phosphate product and a normal
      parathyroid hormone level. A skin biopsy specimen showed necrotic skin and
      subcutaneous fat with foci of calcification around the vessels, findings that
      confirmed the diagnosis of calciphylaxis. The patient then underwent subtotal
      parathyroidectomy and responded with initial improvement; however, her condition
      later deteriorated, and she died of uncontrolled pulmonary hemorrhage.
      CONCLUSION: Systemic calciphylaxis is a rare but devastating complication of end
      stage renal disease. This condition mimics many different disorders; therefore, a
      high index of suspicion is essential for early recognition and diagnosis, which
      is assisted by biopsy specimens of skin lesions. Treatment includes subtotal or
      total parathyroidectomy in conjunction with autotransplantation, administration
      of phosphate binders, aggressive treatment with antibiotics, and lowering of the
      calcium-phosphate product. Even though a successful outcome is possible when this
      disease is recognized early and treated aggressively, the morbidity and mortality
      associated with systemic calciphylaxis still remain high.

PMID- 15251704
TI  - Beta-adrenergic blocking agents in patients with diabetes-- friend and foe.

PMID- 15251705
TI  - Let's get real about actual costs of thyroid testing.

PMID- 15251706
TI  - Human immunodeficiency virus infection.

PMID- 15251707
TI  - Central hypogonadism: distinguishing idiopathic low testosterone from pituitary
      tumors.
AB  - OBJECTIVE: To attempt to determine clinical or hormonal characteristics that
      could help distinguish benign idiopathic low testosterone (ILT) from pituitary
      tumor. METHODS: On retrospective review of medical records of patients
      encountered by Johns Hopkins endocrine staff between 1985 and July 1995, 64
      patients who fulfilled our enrollment criteria--27 men with ILT and 37 patients
      with imaging-proven pituitary tumor--were identified. Men 21 years of age or
      older needed to have had serum testosterone, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), and prolactin levels measured before hormonal
      replacement therapy or pituitary tumor extirpation (or both) and a high-quality
      imaging scan (computed tomography or magnetic resonance imaging) done and
      interpreted by the Johns Hopkins radiology staff. RESULTS: In comparison with men
      who had ILT, men with pituitary tumors had similar serum testosterone levels and
      significantly higher serum levels of LH, FSH, and prolactin. In addition,
      significantly more men with pituitary tumors had visual field abnormalities,
      headaches, and symptoms of hypothyroidism in comparison with the men with ILT. In
      contrast, the group with ILT complained significantly more of impotence, erectile
      dysfunction, and depression than did the group with pituitary tumors. The age at
      initial assessment was comparable in both study groups. CONCLUSION: Although age
      at initial manifestation did not predict the presence of pituitary tumor, the
      group of men with tumors were more likely than those with ILT to have serum
      testosterone levels <150 ng/dL, higher serum gonadotropin and prolactin levels,
      and visual field abnormalities and less likely to have sexual dysfunction.
      Therefore, on the basis of our data, we recommend that men with these findings
      should be referred for a magnetic resonance image to exclude the presence of a
      tumor.

PMID- 15251708
TI  - Weight loss in patients with diabetes treated with a metformin-sulfonylurea
      combination in comparison with twice-daily mixed insulin.
AB  - OBJECTIVE: To investigate whether patients previously treated with insulin or
      sulfonylureas alone can be transferred to a combination of sulfonylureas and
      metformin therapy and realize a prolonged weight loss. METHODS: We conducted a
      retrospective review of medical records to identify three groups of patients with
      type 2 diabetes: group 1, those requiring insulin who had remained on a daily
      regimen of two injections of mixed insulin; group 2, patients whose regimen had
      been changed from sulfonylureas alone to a combination of a sulfonylurea and
      metformin; and group 3, patients whose regimen had been converted from twice
      daily mixed insulin alone to a sulfonylurea-metformin combination. Results
      relative to loss of weight in these three groups were analyzed. RESULTS: For a 12
      month period, no significant weight loss was noted in group 1, and group 2 showed
      a small nonsignificant weight loss in 6 months. Only group 3 had a significant
      weight loss at 3, 6, 9, and 12 months, maximizing at a mean weight loss of 22 lb
      (10 kg) at 12 months. In addition, in those patients in whom data were available,
      a significant weight loss was found at 18 and 21 months. At 21 months, however,
      weight began to increase. Percentage weight loss followed a pattern similar to
      that seen with total weight loss. The proportion of patients losing weight did
      not differ significantly in groups 1 and 2; however, in group 3, after 3 and 12
      months a significant proportion of patients (79% and 86%, respectively) had lost
      weight. Race, gender, or baseline body weight had no effect on weight loss.
      CONCLUSION: From this retrospective study of patients with type 2 diabetes, we
      conclude that conversion from insulin to combination oral therapy with
      sulfonylureas and metformin results in a significant weight loss for up to 21
      months.

PMID- 15251709
TI  - Thromboembolic complications after inferior petrosal sinus sampling in patients
      with cushing's syndrome.
AB  - OBJECTIVE: To heighten the awareness of treating physicians of the potential for
      serious and fatal thromboembolic complications after inferior petrosal sinus
      sampling in patients with Cushing's syndrome. METHODS: We retrospectively
      reviewed inpatient and outpatient medical records for a 12-year period to
      identify patients with Cushing's syndrome who had thromboembolic complications
      after inferior petrosal sinus sampling at a single institution. Case reports of
      affected patients are presented. RESULTS: Of 34 patients with corticotropin
      dependent Cushing's syndrome who underwent inferior petrosal sinus sampling, 2
      had deep venous thrombosis. One of these patients succumbed to pulmonary
      thromboembolism. CONCLUSION: Serious and potentially fatal thromboembolic
      disorders may complicate inferior petrosal sinus sampling. Prospective studies
      should be undertaken to determine the true incidence of deep venous thrombosis
      after this procedure in patients with Cushing's syndrome.

PMID- 15251710
TI  - Resistance to thyroid hormone: report of 2 kindreds with 35 patients.
AB  - OBJECTIVE: To report two kindreds with resistance to thyroid hormone (RTH),
      particularly the clinical and laboratory evolution after thyroidectomy and with
      antithyroid drug treatment. METHODS: Clinical data and thyroid function were
      determined in 82 members from three different generations of both families.
      Unaffected relatives were used as a control group. Response of thyroid
      stimulating hormone (TSH) to the hypothalamic thyrotropin-releasing hormone (TRH)
      was evaluated in five patients and compared with five nonaffected relatives.
      RESULTS: Thirty-five (22 male and 13 female) patients had high serum levels of
      thyroxine and triiodothyronine in conjunction with nonsuppressed TSH. Goiter was
      present in 66% of affected family members; prevalence was 10% in childhood and
      88% in adulthood. The prevalence of goiter was 18% in nonaffected relatives. No
      patient showed evidence of thyroid hypofunction or hyperfunction, and the TSH
      response to TRH was similar to that of nonaffected relatives. The incidence of
      RTH in offspring was 60%, consistent with autosomal dominant transmission. Four
      patients had undergone thyroidectomy, and two required a second operation because
      of recurrence of goiter. Patients who had undergone thyroidectomy had normal or
      near-normal levels of thyroid hormone and very high values of TSH despite thyroid
      hormone therapy. Five patients were treated with antithyroid drugs for 2 to 10
      years, but their thyroid function remained similar to that of nontreated
      patients. CONCLUSION: RTH is a relatively rare and benign condition that can be
      misdiagnosed as hyperthyroidism. The disease is responsible for a high prevalence
      of goiter in affected families. Thyroidectomy and treatment with antithyroid
      drugs are not indicated and may have lifelong implications.

PMID- 15251711
TI  - Euthyroid pretibial myxedema.
AB  - OBJECTIVE: To describe a case of biopsy-proven pretibial myxedema in a man with
      normal thyroid function. METHODS: We present the pertinent clinical and
      laboratory data for the current case and review previously published information
      on pretibial myxedema. RESULTS: Our patient, a 53-year-old man, had the
      characteristic lesions of pretibial myxedema on the anterolateral aspects of his
      calves. Laboratory tests showed normal thyroid function. The thyroid-stimulating
      immunoglobulin value was above normal. No exophthalmos or goiter was present.
      This uncommon dermopathy is typically associated with Graves' disease,
      accompanied by clinical hyperthyroidism, ophthalmopathy, and goiter. CONCLUSION:
      The pathogenesis of pretibial myxedema remains elusive. It is presumed to be an
      autoimmune phenomenon attributable to the presence of serum thyroid-stimulating
      immunoglobulin, although immunofluorescence studies have failed to demonstrate a
      direct role for such an immunoglobulin. Only two other cases of biopsy-proven
      pretibial myxedema in a euthyroid patient were found in the literature.

PMID- 15251712
TI  - Localization of ectopic corticotropin-producing carcinoid tumor with use of
      indium-111 pentetreotide scintigraphy.
AB  - OBJECTIVE: To report on the diagnosis of ectopic corticotropin
      (adrenocorticotropic hormone [ACTH])-producing bronchial carcinoid tumor by
      indium-111 pentetreotide (octreotide scan) scintigraphy. METHODS: We present a
      case of ectopic ACTH syndrome caused by an occult bronchial carcinoid tumor
      arising in a lymph node and review the pertinent literature. RESULTS: Biochemical
      diagnosis of ACTH syndrome can be difficult, and conventional imaging modalities
      often do not demonstrate these small carcinoid tumors. After biochemical proof of
      the presence of ectopic ACTH syndrome in our patient, conventional radiographic
      studies did not demonstrate any lesions. An octreotide scan showed a lesion in
      the lung, which was confirmed surgically. ACTH values returned to normal after
      resection of the lesion, and octreotide scans confirmed the completeness of
      surgical resection. The carcinoid tumor originated in a lymph node outside the
      bronchus. The differential diagnosis of ACTH syndrome, the localization of
      ectopic ACTH-producing tumors, the bronchial carcinoids, and the uniqueness of
      the carcinoid tumor arising in a lymph node are briefly discussed. CONCLUSION:
      Octreotide scintigraphy is useful in localizing occult carcinoid tumors and can
      be used in the follow-up of patients after successful removal of these tumors.

PMID- 15251713
TI  - An unusual sellar mass--solitary plasmacytoma.
AB  - OBJECTIVE: To describe a case of solitary intrasellar plasmacytoma in a patient
      with a preoperative diagnosis of a nonfunctioning pituitary adenoma. METHODS: A
      case of a solitary intrasellar plasmacytoma is presented, in which the clinical
      and laboratory findings are detailed and the response to treatment is discussed.
      Pertinent reports from the literature are reviewed. RESULTS: A 53-year-old woman
      came to the neurology clinic with complaints of frontal headaches and
      intermittent blurry vision. Physical examination showed no remarkable findings.
      Computed tomography revealed an enhancing sellar and suprasellar mass, with
      extension into the sphenoid and cavernous sinuses. The patient had a preoperative
      diagnosis of a clinically nonfunctioning pituitary adenoma and underwent
      transsphenoidal resection. The biopsy specimen was heavily infiltrated with
      abnormal plasma cells, which stained exclusively for lambda light chain
      immunoglobulins. An extensive investigation failed to show evidence of multiple
      myeloma. In view of these findings, the diagnosis of solitary extramedullary
      plasmacytoma was made. Postoperatively, the patient received radiotherapy to the
      pituitary and has remained free of disease for 7 years. Review of the world
      literature disclosed only 17 previous reports of patients in whom a solitary
      plasmacytoma or multiple myeloma first appeared as a sellar mass. In each case,
      the plasmacytoma mimicked a clinically nonfunctioning pituitary adenoma.
      CONCLUSION: Parasellar plasmacytomas are often mistaken for a nonfunctioning
      pituitary adenoma. The diagnosis is difficult to make in the absence of overt
      systemic myeloma. Nevertheless, normal pituitary function associated with severe
      destruction of the pituitary fossa, cranial neuropathies, and diabetes insipidus
      are clues that the primary lesion is outside the pituitary gland itself. The
      current patient is unique in terms of prolonged survival in the absence of
      systemic myeloma. Perhaps those patients with progression of disease did not have
      extramedullary tumors because such lesions rarely progress to overt myelomatous
      disease.

PMID- 15251714
TI  - Adrenal insufficiency--an unusual cause of shock in postoperative patients.
AB  - OBJECTIVE: To remind physicians that adrenal insufficiency can cause
      postoperative shock and that the manifestations are difficult to distinguish from
      those of sepsis. METHODS: We present detailed case reports of three patients who
      had hyperdynamic shock in the surgical intensive-care unit and describe their
      response to the cosyntropin stimulation test. RESULTS: All three patients were
      diagnosed as having adrenal insufficiency with use of the cosyntropin stimulation
      test. Two of the three patients rapidly recovered; however, because of delay in
      the diagnosis of adrenal insufficiency, the third patient succumbed to
      multisystem organ failure. CONCLUSION: The cases presented highlight the need to
      exclude adrenal insufficiency as a possible cause of hyperdynamic circulatory
      shock, particularly when no clear-cut diagnosis exists. Early recognition of
      adrenal insufficiency is important and can result in reversal of shock and
      prevention of death. Adrenal insufficiency can be diagnosed through screening
      random cortisol levels and by use of the cosyntropin stimulation test. Patients
      in addisonian crisis often respond to the first dose of glucocorticoid with
      dramatic improvement in blood pressure and systemic vascular resistance.
      Administration of glucocorticoid can thus lead to improved organ perfusion and
      recovery of organ function. Delays in diagnosis and treatment of acute
      hypoadrenalism can have a fatal outcome.

PMID- 15251715
TI  - The syndrome of resistance to thyroid hormone, misdiagnosed and treated as
      thyrotoxicosis.
AB  - OBJECTIVE: To report two cases of resistance to thyroid hormone and to promote
      increased awareness of this syndrome, which is frequently misdiagnosed and
      incorrectly treated. METHODS: We describe a young woman and her father, both of
      whom were diagnosed at a younger age as having thyrotoxicosis and were treated
      with thyroidectomy and radioactive iodine. Both patients later proved to have
      resistance to thyroid hormone and required supraphysiologic doses of
      levothyroxine to normalize the thyroid-stimulating hormone (TSH) while remaining
      euthyroid. RESULTS: Laboratory evaluation revealed increased serum total
      thyroxine and triiodothyronine levels as well as normal to increased TSH levels.
      The free alpha sub-unit/TSH ratio was normal, and magnetic resonance imaging of
      the pituitary gland showed no tumor. Metabolic studies in the daughter, with use
      of graded doses of triiodothyronine, supported the diagnosis. CONCLUSION: Both
      patients shown to have resistance to thyroid hormone were misdiagnosed and
      inappropriately treated in the past. The resultant hypothyroidism has been
      difficult to treat, particularly in the father who has coronary artery disease.

PMID- 15251716
TI  - Thyroid hormones and illness.
AB  - OBJECTIVE: To review illness-associated changes in thyroid hormone levels with
      respect to the alterations in metabolism, regulation, and transport of thyroid
      hormones present in such a setting. METHODS: We summarize normal pituitary
      thyroid function and categorize the types of changes that have been noted during
      illness. In addition, we examine studies that have addressed the metabolic status
      of patients with low thyroid hormone levels and the potential utility of thyroid
      hormone treatment in severely ill patients. RESULTS: The finding of altered
      thyroid hormone levels in hospitalized patients confirms the participation of
      these factors in the adaptive response to illness. Thyroid hormone alterations
      that occur during illness can be classified into three categories: (1) decreased
      production of triiodothyronine, (2) decreased serum binding of thyroid hormones,
      and (3) decreased secretion of thyrotropin. Study of these hormonal changes has
      provided insight into normal thyroid hormone regulation and metabolism as well as
      into neuroendocrine adaptations to illness. CONCLUSION: It seems reasonable to
      conclude that illness-associated changes in thyroid hormone levels are generally
      beneficial to the patient as a whole; however, the possibility of concomitant
      regional or individual tissue hypothyroidism exists. Conclusions about the
      potential utility of pharmacologic administration of triiodothyronine in selected
      diseases and clinical settings must await additional clinical trials. Finally,
      the predictable occurrence of altered thyroid hormone levels in hospitalized
      patients necessitates caution in both the selection and the interpretation of
      thyroid hormone tests in this patient population.

PMID- 15251717
TI  - Combination therapy with insulin and metformin.
AB  - OBJECTIVE: To review the clinical usefulness of combination therapy with insulin
      and metformin. METHODS: Basic considerations about the use of insulin in non
      insulin-dependent diabetes mellitus (NIDDM) and the interaction of metformin with
      insulin are outlined. The clinical documentation of this therapeutic strategy is
      reviewed, with emphasis on controlled studies. In addition, the use of this drug
      combination in insulin-dependent diabetes mellitus (IDDM) is briefly addressed.
      RESULTS: Insulin is used in patients with NIDDM when adequate plasma glucose
      control can no longer be maintained by orally administered agents. Metformin
      ameliorates insulin resistance, reduces hyperinsulinemia, and counteracts weight
      gain. It exerts an insulin-sparing and antihyperglycemic effect and may improve
      cardiovascular risk factors. Although these effects have been demonstrated
      consistently in several controlled studies, relatively few patients have been
      treated with insulin + metformin (with or without sulfonylurea). The combination
      is well tolerated, commonly used, and approved in several countries. No specific
      guidelines have been established for selection of patients, but obese patients
      with NIDDM who are receiving high doses of insulin are likely to benefit.
      Patients whose diabetes is poorly controlled by sulfonylurea or by combination
      oral therapy, not previously treated with insulin, may also be suitable
      candidates. Insulin administered at bedtime is a feasible approach, and a daily
      dose of 1.5 to 2.5 g of metformin seems adequate. Although the application may be
      questionable, metformin can also be added to insulin in the treatment of selected
      patients with IDDM. CONCLUSION: Metformin is effective in conjunction with
      insulin in NIDDM. Because of its action on insulin resistance, it might be a more
      suitable adjunct to insulin than sulfonylurea in obese patients with NIDDM who
      are receiving high insulin doses, but it has been less well studied.

PMID- 15251718
TI  - Type 2 diabetes mellitus in children.
AB  - OBJECTIVE: To provide an overview of type 2 diabetes in children and discuss
      short-term and long-term management strategies. METHODS: We review the
      distinction among various types of diabetes mellitus as they apply to children.
      In addition, we discuss determining the precise diagnosis between the two major
      variants--type 1 and type 2 diabetes--and clinical management of type 2 diabetes
      in children. RESULTS: A dramatic increase in the incidence of type 2 diabetes in
      children has been noted, which is commensurate with an overall increase in
      obesity. In Arizona, this trend has been similar to that reported in Ohio and
      Arkansas. Glucose toxicity of the pancreas, which occurs with chronic
      hyperglycemia and impairs insulin secretion, may lead to manifestation of florid
      diabetic ketoacidosis and requires insulin therapy at diagnosis. For successful
      long-term management of type 2 diabetes in a child, a program that includes
      weight reduction must be implemented. CONCLUSION: Obesity-related diabetes is
      increasing at an alarming rate in children. Physicians responsible for the care
      for pediatric patients should be aware of this trend and should become familiar
      with management strategies for type 2 diabetes.

PMID- 15251719
TI  - Treatment of childhood and adolescent obesity.

PMID- 15251720
TI  - Inpatient intervention in an indigent, minority population with uncontrolled
      diabetes.
AB  - OBJECTIVE: To study whether a program of brief, intensive, inpatient intervention
      could improve glycemic control in an indigent, minority population with
      uncontrolled diabetes unresponsive to outpatient treatment. METHODS: Patients
      with uncontrolled diabetes unresponsive to treatment in our outpatient Diabetes
      Clinic were admitted to our inpatient Diabetes Unit, where their care was
      directed by the Diabetes Team (an attending diabetologist, an endocrinology
      fellow, two nurses, and two nutritionists). Of 108 patients admitted, data were
      available for 96. Patients from minority populations constituted 91.7% of the
      group. All patients were indigent. The mean duration of stay was 4.3 days. After
      dismissal, patients underwent follow-up again in our Diabetes Clinic. During the
      540-day follow-up period, 25 patients were electively readmitted when
      satisfactory improvement in glycemic control was not achieved. Hemoglobin A1c
      levels were averaged and plotted for the group at defined time points up to 360
      days before admission and up to 540 days after admission. RESULTS: During the
      year before admission, hemoglobin A1c increased slowly from 10.1 +/- 0.3% (mean
      +/- standard error) at day -360 to 10.3 +/- 0.2% at day -210 (F5 = 29; P<0.01)
      and then rapidly to 11.4 +/- 0.2% at admission (F7 = 1,541; P<0.001). After
      admission, hemoglobin A1c declined rapidly to 9.5 +/- 0.2% at day 90 (F4 = 121;
      P<0.005), plateaued at that level until day 240, and then declined again slowly
      to 9.0 +/- 0.3% at day 540, the end of the follow-up period (F10 = 70; P<0.01).
      All hemoglobin A1c levels 30 days or more after admission were significantly
      lower than the mean level at admission (P<0.05 at day 30 and P<0.001 from day 45
      to day 540). CONCLUSION: Brief, intensive, inpatient intervention in an indigent,
      minority population with uncontrolled diabetes unresponsive to outpatient
      treatment produced and sustained a significant improvement in glycemic control.
      This mode of treatment is a practical approach to achieving the improvement in
      glycemic control that the Diabetes Control and Complications Trial demonstrated
      to be effective in delaying the onset and slowing the progression of diabetic
      retinopathy, nephropathy, and neuropathy.

PMID- 15251721
TI  - The combination of insulin and metformin in treatment of non-insulin-dependent
      diabetes mellitus.
AB  - OBJECTIVE: To assess whether, in the treatment of non-insulin-dependent diabetes
      mellitus (NIDDM), (1) metformin in conjunction with insulin can safely cause a
      decrease in glycosylated hemoglobin (HbA1c) to 7% or less and (2) this
      combination therapy may result in weight loss and lower insulin dose in
      comparison with insulin treatment alone. METHODS: Forty patients with NIDDM being
      treated with insulin on their first visit to the Diabetes Center were identified
      by retrospective review of medical records of all patients encountered during a 1
      year period. These patients were classified into groups who were receiving
      insulin only (group 1) or insulin + metformin (group 2) at the most recent visit.
      Group 2 was subdivided into those with a body mass index of either =30 kg/m 2
      (group 2A) or >30 kg/m 2 (group 2B). Blood glucose, HbA1c, insulin dose, and
      weights were analyzed from their initial and most recent visits. RESULTS: HbA1c
      decreased from 10 +/- 2.7% to 7 +/- 1.1% (P<0.01) in group 1 and from 9.8 +/-
      2.1% to 7.2 +/- 1.4% (P<0.01) in group 2. The magnitude of decrease in HbA1c,
      however, was not different between the two groups. Total insulin dose increased
      from 40 (33 to 50) U/day to 58 (41 to 67) U/day (P<0.05) in group 1 and from 63
      (42 to 118) U/day to 67 (50 to 96) U/day in group 2 (not significantly
      different). The median increase in insulin dose was 8 U in group 1, whereas the
      median decrease was 3 U in group 2 (P<0.05). Similar decreases were noted in
      group 2A. The decrease in insulin dose was inversely related to the initial
      insulin dose per kilogram of body weight in group 2 (r = -0.5; P<0.01). Patients
      in group 1 had an increase in weight from 75.0 +/- 8.6 kg to 77.7 +/- 9.0 kg
      (P<0.01), whereas weight decreased from 100.4 +/- 24.2 kg to 98.5 +/- 22.3 kg in
      group 2 (P<0.05). A decrease in weight was seen even in group 2A. The increase in
      weight was 3 +/- 3.3 kg in group 1, whereas weight decreased by 1.9 +/- 3.9 kg in
      group 2 (P<0.01). CONCLUSION: Insulin + metformin is safe and is as effective as
      insulin alone in improving glycemic control in obese and nonobese patients with
      NIDDM. This combination therapy, however, lowers insulin dose and promotes weight
      loss, which may be of importance in decreasing the cardiovascular risk factors in
      these subjects.

PMID- 15251722
TI  - Incidental atypical pheochromocytoma in sporadic type IIb von Hippel-Lindau
      disease.
AB  - OBJECTIVE: To describe the features of an incidentally discovered atypical
      pheochromocytoma in an asymptomatic patient with normal blood pressure and the de
      novo appearance of sporadic type IIB von Hippel-Lindau (VHL) disease. METHODS: We
      review the clinical manifestations, radiographic findings, and unusual features
      of a large, atypical pheochromocytoma diagnosed in a patient with the rare type
      IIB phenotype of VHL disease. RESULTS: A 46-year-old man, who sought medical
      assistance in the emergency department after a motorcycle accident, had an
      abdominal roentgenogram that revealed extensive left suprarenal calcification.
      Computed tomography of the abdomen demonstrated a densely calcified left adrenal
      mass, bilateral renal cysts, and pancreatic calcifications. The patient was
      normotensive and asymptomatic and had no history of hypertension. He had
      undergone resection of a cerebellar hemangioblastoma at age 36 years and a
      partial left nephrectomy for a renal cyst at age 7 years. Routine biochemical
      screening demonstrated increased urinary vanillylmandelic acid and
      normetanephrine levels as well as an elevated plasma norepinephrine level. The
      adrenal mass was notable for the absence of increased signal intensity on T2
      weighted magnetic resonance images. The patient was diagnosed with the type IIB
      phenotype of VHL disease and underwent resection of a 10.5-cm, 124-g benign
      pheochromocytoma. CONCLUSION: Our case emphasizes the importance of recognizing
      that pheochromocytoma may occur in association with sporadic VHL disease, that
      not all pheochromocytomas have an increased signal intensity on T2-weighted
      magnetic resonance images, and that routine biochemical testing for
      pheochromocytoma is important in all patients with an adrenal "incidentaloma."

PMID- 15251723
TI  - False-positive ethylene glycol levels in patients with diabetic ketoacidosis.
AB  - OBJECTIVE: To describe two patients with diabetic ketoacidosis and positive
      ethylene glycol levels and to call attention to the possibility of a false
      positive ethylene glycol determination in patients with ketoacidosis. METHODS:
      Clinical manifestations and laboratory tests in the two patients were summarized.
      Serum specimens for both patients were analyzed for ethylene glycol, serum
      ketones, glucose, osmolality, pH, and electrolytes. RESULTS: Respective
      laboratory findings in our two patients were as follows: serum glucose levels,
      56.4 and 45.7 mmol/L; serum acetone, positive in 1:80 and 1:128 dilution; serum
      osmolality, 366 and 377 mmol/kg; pH, 6.9 and 7.2; and ethylene glycol, 3.46 and
      2.45 mmol/L. CONCLUSION: Neither of these two elderly women had ingested ethylene
      glycol; nevertheless, both had positive results for ethylene glycol on a blood
      toxicology screen. Review of the literature demonstrates that false-positive
      ethylene glycol levels can be detected in patients with ketoacidosis. This
      information is documented in this report and should alert practicing physicians
      to such a possibility.

PMID- 15251725
TI  - Acromegaly and non-Hodgkin's lymphoma.
AB  - OBJECTIVE: To present the fourth case report of development of a non-Hodgkin's
      lymphoma in a patient with active acromegaly. METHODS: We describe the clinical,
      laboratory, and imaging findings in a patient with untreated acromegaly in whom a
      large cell non-Hodgkin's lymphoma developed. RESULTS: Acromegaly is associated
      with several comorbid conditions. Among these is a higher incidence of several
      types of visceral malignant lesions, especially carcinoma of the colon. Growth
      hormone stimulates the hepatic production of somatomedins, such as insulin-like
      growth factors, which are known promoters of human growth and have also been
      implicated in tumorigenesis. In recent years, several cases of
      lymphoproliferative diseases have also been noted in patients with acromegaly.
      These conditions include multiple myeloma, lymphoma, and leukemia; three previous
      cases of non-Hodgkin's lymphoma have been described. In our patient, a 57-year
      old man with acromegaly, magnetic resonance imaging of the pituitary gland
      disclosed a large intrasellar mass. Large cell non-Hodgkin's lymphoma was
      diagnosed. Six months of chemotherapy yielded complete remission. CONCLUSION: An
      additional case of non-Hodgkin's lymphoma in a patient with acromegaly supports
      the accumulating evidence of an increased risk for development of cancer in such
      patients.

PMID- 15251724
TI  - Successful long-term management of a gonadotroph adenoma with bromocriptine.
AB  - OBJECTIVE: To report the successful 10-year management of a gonadotroph
      macroadenoma with bromocriptine and review the management of gonadotroph adenomas
      with bromocriptine. METHODS: We present a case and review the pertinent
      literature. The effectiveness of bromocriptine in the management of gonadotroph
      adenomas is evaluated. RESULTS: A 62-year-old man was found to have a pituitary
      tumor after seeking medical assistance because of a 6-month history of headaches
      and blurred vision. He had decreased visual acuity and bitemporal field defects.
      Serum follicle-stimulating hormone (FSH) levels were increased, whereas serum
      luteinizing hormone and total testosterone levels were normal. Treatment with
      bromocriptine resulted in a decrease in serum FSH levels, complete resolution of
      his symptoms, and considerable improvement in his visual acuity and visual field
      defects. Treatment with only bromocriptine for 10 years resulted in maintenance
      of normal serum FSH levels and no recurrence of symptoms. CONCLUSION: In the
      management of a gonadotroph adenoma, we recommend consideration of a therapeutic
      trial of bromocriptine. In cases that are refractory to this therapy, surgical
      treatment or external pituitary irradiation could then be used.

PMID- 15251726
TI  - Radioiodine treatment of thyroid cancer with the aid of recombinant human
      thyrotropin.
AB  - OBJECTIVE: To update endocrinologists on the use of recombinant human thyrotropin
      (thyroid-stimulating hormone or TSH) (rhTSH) in thyroid diseases, with an
      emphasis on thyroid cancer. METHODS: We reviewed the available literature on
      potential uses of rhTSH, including published studies and case reports. RESULTS:
      Clinical trials have shown that rhTSH injections stimulate radioiodine uptake
      into normal and malignant thyroid tissue almost as well as that found in the
      hypothyroid state. The benefit to the athyreotic patient is the avoidance of the
      disability of hypothyroidism. When rhTSH is used in the doses currently
      recommended for scanning, few negative side effects occur. The more rapid
      clearance of iodine in the euthyroid state, however, may necessitate the use of
      more radioiodine to achieve the same amount of irradiation to metastatic lesions.
      We have used rhTSH for both dosimetric studies and therapy. This approach is
      essential in patients who cannot make sufficient endogenous TSH (because of
      hypothalamic-pituitary disease or medications that suppress TSH). Other patients
      with widespread metastatic lesions who have serious complications when allowed to
      become hypothyroid also benefit from rhTSH. Finally, we have found that rhTSH may
      provide new insights into the biologic features of thyroid cancer when used in
      combination with positron emission tomographic scanning. Use in the treatment of
      nonmalignant thyroid conditions such as toxic multinodular goiter is also
      feasible. CONCLUSION: Overall, rhTSH provides a new and clinically important
      advance for patients with thyroid disease, especially thyroid cancer.

PMID- 15251727
TI  - Thyroid cancer follow-up.

PMID- 15251728
TI  - It takes a multidisciplinary team to treat diabetes.

PMID- 15251729
TI  - Glycated hemoglobin in insulinoma.
AB  - OBJECTIVE: To determine whether preoperative levels of glycated hemoglobin (GHb)
      are lower in patients with functioning insulinoma and, if so, whether a distinct
      separation of GHb values from those in control subjects might serve for
      diagnosis. METHODS: We examined preoperative GHb in consecutive patients (who had
      this measurement done) with surgically confirmed insulinoma for the period 1983
      (when the current method became available for routine use) through 1996.
      Hemoglobin A(1) (HbA(1)) was measured by the Isolab Glyc-Affin Test System
      (normal range, 4 to 7%). We studied 64 patients with insulinoma (40 women and 24
      men; median age, 47.5 years; age range, 21 to 79) and 38 control subjects (25
      women and 13 men; median age, 42.5 years; age range, 20 to 83) considered not to
      have a hypoglycemic disorder on the basis of normal results of a supervised 72
      hour fast. RESULTS: HbA(1) was significantly lower in patients with insulinoma
      (median, 4.7%; range, 2.7 to 6.9%) than in control subjects (median, 5.3%; range,
      4.1 to 6.4%) (P<0.001, two-tailed rank sum test). Among 15 patients with
      insulinoma treated with diazoxide preoperatively, HbA(1) was higher (median,
      4.8%; range, 4.2 to 6.9%) than in patients not treated with diazoxide (median,
      4.6%; range, 2.7 to 5.7%), although the difference was not statistically
      significant (P = 0.08). CONCLUSION: Because of considerable overlap in HbA(1)
      values, no GHb value was diagnostic for insulinoma; however, 16 of 64 patients
      (25%) with insulinoma had HbA(1) values below the lowest value (4.1%) in control
      subjects. Thus, HbA(1) values less than 4.1% in patients with possible insulinoma
      are strongly indicative of that disorder.

PMID- 15251730
TI  - Localization of abnormal parathyroid tissue with use of technetium-99m-sestamibi.
AB  - OBJECTIVE: To evaluate the efficacy of "double-phase" technetium-99m-sestamibi
      scanning in the localization of abnormal parathyroid tissue in patients with
      hyperparathyroidism. METHODS: We present a prospective review of patients with
      hyperparathyroidism seen at a university teaching hospital between June 1994 and
      May 1997. Twenty-four patients entered into the study underwent preoperative
      localization with double-phase technetium-99m-sestamibi. The nuclear medicine
      results were compared with the operative findings. RESULTS: The Tc-99m-sestamibi
      scan correctly identified the location of single parathyroid adenomas in 22
      patients (100%). Of the other two patients, both with diffuse parathyroid
      hyperplasia, one had a negative sestamibi scan and one had only the two inferior
      parathyroid glands localized on the sestamibi scan. One patient with recurrent
      hypercalcemia, who previously underwent total parathyroidectomy and parathyroid
      autotransplantation into the left forearm, had activity localized to that forearm
      but not to the neck. Subsequently, hyperplastic parathyroid tissue was
      successfully removed from the transplantation site. Another patient, who had
      previously undergone two unsuccessful surgical explorations prompted by
      hyperparathyroidism, had sestamibi localization of an adenoma inferior and medial
      to the right submandibular gland. The third surgical exploration disclosed a
      large adenoma medial to the carotid artery, just below the angle of the jaw. In
      two elderly, debilitated women with positive scans, adenomas were removed with
      use of local anesthesia. Of 22 patients in whom long-term follow-up was
      available, 21 remained normocalcemic for a mean period of 11.4 +/- 1.7 months
      postoperatively. One patient in whom hyperplastic parathyroid tissue had been
      removed from the left forearm had recurrence of hypercalcemia 1 year after
      operation. CONCLUSION: Technetium-99m-sestamibi scanning is a reliable method for
      identifying parathyroid adenomas but not as helpful in localizing hyperplastic
      parathyroid glands. The precise localization of an adenoma simplifies surgical
      exploration and in selected patients may allow excision of the adenoma under
      local anesthesia. Tc-99msestamibi scanning has become the preferred method for
      noninvasive localization of abnormal parathyroid glands.

PMID- 15251731
TI  - Unusual manifestations of cushing's syndrome in a multiple endocrine neoplasia
      type I kindred.
AB  - OBJECTIVE: To describe two unusual cases of Cushing's syndrome in a kindred with
      multiple endocrine neoplasia type I (MEN I). METHODS: The clinical and laboratory
      data as well as follow-up course of the two patients are reviewed in detail.
      RESULTS: Our first patient with a history of MEN I had hypercortisolism and
      computed tomographic evidence of a right adrenal mass (8.5 by 11 cm) extending
      into the inferior vena cava as well as multiple pulmonary nodules. He was
      diagnosed with Cushing's syndrome attributable to metastatic adrenal cancer that
      progressed despite chemotherapy. He died 2 years later. His son, who was also
      diagnosed with MEN I, had adrenocorticotropic hormone-dependent Cushing's
      syndrome. The plasma corticotropin-releasing hormone (CRH) level was high;
      magnetic resonance imaging showed normal pituitary findings but an islet cell
      tumor of the pancreas. The islet cell tumor was resected, and the patient's
      urinary cortisol declined to upper limits of normal. CRH was detected in the
      tissue, and the patient was thought to have Cushing's syndrome as a result of a
      CRH-secreting islet cell tumor. One year later, however, his Cushing's syndrome
      recurred. Inferior petrosal sinus sampling suggested a pituitary source, and the
      patient underwent transsphenoidal hypophysectomy. Histopathologic examination did
      not reveal pituitary hyperplasia or microadenoma, but the patient was cured of
      his Cushing's syndrome. CONCLUSION: Cushing's syndrome is a rare initial
      manifestation of MEN I. We report two unusual causes of Cushing's syndrome in MEN
      I--that is, adrenal cancer and a probable CRH-secreting islet cell tumor. The
      natural history of Cushing's syndrome in MEN I is not known; further studies
      should be conducted.

PMID- 15251732
TI  - Increased serum carcinoembryonic antigen levels as an early sign of medullary
      thyroid carcinoma.
AB  - OBJECTIVE: To emphasize the potential association between increased levels of
      carcinoembryonic antigen (CEA) and the presence of medullary thyroid carcinoma
      (MTC). METHODS: We present two case reports of this association, including long
      term serial measurements of CEA in one patient. RESULTS: CEA is a tumor marker
      often associated with colon cancer. In recent years, increased CEA in plasma has
      been reported in patients with other cancers. Diagnoses of MTC in two patients
      were preceded by increased CEA levels (for 6 years in one patient). Because CEA
      levels returned to normal after thyroidectomy, MTC may have been the cause of the
      increases. CONCLUSION: In patients with increased plasma CEA levels, MTC should
      be considered in the differential diagnosis even if thyroid palpation is
      nonrevealing and thyroid function is normal.

PMID- 15251733
TI  - Successful outcome with methimazole and lithium combination therapy for
      propylthiouracil-induced hepatotoxicity.
AB  - OBJECTIVE: To assess the efficacy and safety of combination therapy with
      methimazole and lithium carbonate in management of severe thyrotoxicosis and
      propylthiouracil-induced hepatotoxicity. METHODS: We present a case report of a
      patient with severe thyrotoxicosis and worsening liver dysfunction after
      propylthiouracil therapy, and we review the pertinent literature. RESULTS: In a
      49-year-old man with severe thyrotoxicosis and propylthiouracil-induced
      hepatotoxicity, indices of liver function continued to increase despite
      discontinuation of propylthiouracil treatment. Adjunctive therapy with
      methimazole and lithium resulted in prompt remission of clinical manifestations
      and normalization of thyroid hormone indices, as well as a gradual reversal of
      liver dysfunction. CONCLUSION: Adjunctive therapy with methimazole and lithium is
      synergistic in promptly achieving a euthyroid state. Therefore, this combination
      therapy provides a safe and effective alternative option in patients with
      thyrotoxicosis associated with propylthiouracil-induced hepatotoxicity.

PMID- 15251734
TI  - Hyperthyroidism during lithium therapy for depression.
AB  - OBJECTIVE: To report three cases of hyperthyroidism encountered within a period
      of 32 months in patients receiving lithium therapy for depression. METHODS: Three
      detailed case reports are presented, and the related literature is discussed.
      RESULTS: Although hypothyroidism during lithium therapy is well recognized and
      documented, appearance of cases of hyperthyroidism during lithium therapy is
      considered uncommon. The antithyroid effect of lithium through inhibition of
      generation of cyclic adenosine monophosphate tends to mask the underlying
      hyperthyroidism. Nevertheless, during a 32-month period, three cases of
      hyperthyroidism were encountered in patients who had received lithium treatment
      (900 to 1,200 mg/day) for 7 months to 17 years. These patients had symptoms of
      heat intolerance, palpitations, and tremor, and they were subsequently treated
      successfully with radioactive iodine. CONCLUSION: Most likely, cases of
      hyperthyroidism that occur during lithium therapy may be under-diagnosed,
      underreported, or both.

PMID- 15251735
TI  - Renal cell carcinoma metastatic to the pituitary gland: clinical manifestations
      and successful treatment with transsphenoidal resection.
AB  - OBJECTIVE: To describe two cases of metastatic involvement of the pituitary gland
      by renal cell carcinoma (RCCA) and review the medical literature regarding this
      entity. METHODS: We present two case reports and discuss the published literature
      to illustrate the clinical findings, radiographic features, and recommended
      management of RCCA metastatic to the pituitary gland. RESULTS: During a 12-month
      period, we encountered two patients, one with visual deficits and both with
      anterior pituitary dysfunction, who had large sellar lesions that were
      histologically proved to be RCCA. Both patients were successfully treated with
      transsphenoidal surgical resection of the lesion, one of whom is alive and well
      more than 2 years later. A pituitary metastatic tumor is an uncommon complication
      of RCCA; it may be difficult to diagnose and potentially fatal. Anterior
      pituitary dysfunction and visual disturbances are more common initial features
      than is diabetes insipidus, in contrast to pituitary metastatic involvement from
      other tumors. CONCLUSION: Transsphenoidal resection is a safe and effective
      method of treatment of RCCA metastatic to the pituitary gland.

PMID- 15251736
TI  - Multiple endocrine neoplasia and polyglandular autoimmune syndrome: a new
      association.
AB  - OBJECTIVE: To report a new association between polyglandular autoimmune syndrome
      and multiple endocrine neoplasia. METHODS: We present a detailed case report and
      discuss the various types of polyglandular failure and multiple endocrine
      neoplasia. RESULTS: A 56-year-old woman with a past history of primary
      hypothyroidism and impaired glucose tolerance was admitted to the hospital for
      removal of renal staghorn calculi. In addition to the presence of mucocutaneous
      candidiasis, vitiligo, and macroglossia, the patient was found to have truncal
      obesity, a "buffalo hump," and supraclavicular fat pads. Subsequent workup
      confirmed the presence of Cushing's disease and primary hyperparathyroidism.
      CONCLUSION: A hitherto unreported association between polyglandular autoimmune
      syndrome type II and multiple endocrine neoplasia type I is documented in our
      current patient.

PMID- 15251737
TI  - Troglitazone: current therapeutic role in type 2 diabetes mellitus.
AB  - OBJECTIVE: To describe the role of troglitazone in the treatment of non-insulin
      dependent diabetes mellitus. METHODS: The potential mechanisms of action of the
      thiazolidinediones are outlined, and studies that have been conducted in animals
      and in humans are reviewed. RESULTS: Although the precise mode of action of
      troglitazone, a thiazolidinedione, is unknown, this agent is an insulin
      sensitizer that has been shown to decrease fasting insulin, fasting plasma
      glucose, and blood pressure levels in humans. The effect of troglitazone is
      progressively greater over time; in several studies, the maximal action occurred
      as long as 12 weeks after initiation of treatment. The usual daily dose is 200 to
      600 mg, and no dosage adjustment is necessary in patients with renal
      insufficiency. Adverse events, including fluid retention and hepatic dysfunction,
      may limit the utility of troglitazone in some clinical situations. CONCLUSION:
      Both in monotherapy and in combination with sulfonylureas, insulin, or metformin,
      troglitazone has proved to be an effective agent for the treatment of type 2
      diabetes mellitus.

PMID- 15251738
TI  - Health-care charges generated by patients with diabetes.
AB  - For assessment of health-care charges generated by patients with diabetes, 50
      patients (25 who were older than 65 years and 25 who were age 65 or younger)
      whose primary care had been delivered between 1990 and 1995 by a single
      diabetologist were randomly selected. Institutional health-care bills were
      accessed from all but three medical center billing offices (dermatology,
      psychiatry, and radiation oncology areas did not respond). For each dollar billed
      by endocrinology, the hospital billed 25.90 dollars, other medical specialties
      2.70 dollars, surgery 1.10 dollars, radiology 0.70 dollars and pathology 0.60
      dollars. The charges generated by the endocrinologist-diabetologist account for
      approximately 3% of the total charges for the care of the patient with diabetes
      mellitus in a fee-for-service practice. Although the endocrinologist
      diabetologist provides the most cost-effective medical service for patients with
      diabetes, low reimbursement jeopardizes the practice of this subspecialty.

PMID- 15251739
TI  - Role of eye muscle antibody measurement in diagnosis of thyroid-associated
      ophthalmopathy: a laboratory update.
AB  - OBJECTIVE: To review the current role of measurement of serum eye muscle
      antibodies in thyroid-associated ophthalmopathy (TAO). METHODS: We conducted
      laboratory studies to determine the prevalences of serum autoantibodies reactive
      with eye muscle antigens in patients with active and inactive TAO, Graves'
      hyperthyroidism, and Hashimoto's thyroiditis as well as in normal subjects.
      RESULTS: The two antigens most often recognized in immunoblotting with crude
      human or porcine eye muscle membranes by serum autoantibodies in patients with
      TAO are eye muscle membrane proteins of 55 and 64 kd. One 64-kd eye muscle
      protein has recently been cloned by screening a human eye muscle expression
      library with two different antibody probes and identified from a computer gene
      bank search as the calcium-binding protein calsequestrin. A fragment of a 220-kd
      eye muscle protein, called G2s, has also been cloned by screening the eye muscle
      library with affinity-purified antibodies reactive with a 55-kd eye muscle
      membrane protein. The prevalences of autoantibodies reactive with these two
      antigens in our study groups were as follows. Antibodies against calsequestrin
      were detected in 38% of patients with TAO for <1 year, in 17% of those with TAO
      for >3 years, in 17% of patients with Graves' hyperthyroidism without
      ophthalmopathy, in 12% of patients with Hashimoto's thyroiditis without
      ophthalmopathy, and in 21% of normal subjects. Antibodies reactive with the 64-kd
      protein were demonstrated in 62% of patients with recent-onset active TAO, in 33%
      with eye disease for >3 years, in 39% of patients with Graves' hyperthyroidism
      without ophthalmopathy, in 25% of patients with Hashimoto's thyroiditis, and in
      16% of normal control subjects. Antibodies reactive with G2s fusion protein were
      detected in 67% of patients with recent-onset active TAO, in 46% of patients with
      Graves' hyperthyroidism, and in 20% of normal subjects. Antibodies reactive with
      the parent protein, of which G2s is a fragment, may be markers of early eye
      muscle swelling and inflammation, whereas those reactive with the 64-kd protein
      and, less often, calsequestrin are associated with established eye disease.
      CONCLUSION: Measurement of serum eye muscle antibodies is recommended as an aid
      to the early diagnosis of ophthalmopathy in predisposed patients and first-degree
      relatives of patients with TAO as well as to monitor active or progressive eye
      disease.

PMID- 15251740
TI  - Determination of insulin requirements: excessive insulin dosages common in type 1
      diabetes mellitus.
AB  - OBJECTIVE: To report our experience of determining insulin requirements for
      initiating continuous subcutaneous insulin infusion (CSII) pump therapy, using an
      algorithm for intravenous administration of insulin, in patients with poorly
      controlled diabetes. METHODS: We describe assessment of insulin requirements and
      analyze data from 27 consecutive admissions. All patients had type 1 diabetes
      mellitus and were being converted to CSII pump therapy. Twenty-four-hour
      intravenous insulin requirements were used to initiate CSII pump therapy, and
      further dose adjustments were undertaken, to optimize glycemic control. Basal,
      bolus, and total daily insulin requirements were calculated before, during, and 3
      months after conversion to CSII therapy. RESULTS: At entry, the mean
      glycohemoglobin was 11.2% (normal, 5.0 to 8.0%), and the mean daily insulin dose
      were 45.8 U (0.59 U/kg). Calculated daily insulin requirements using an algorithm
      for intravenously administered insulin were 37.3 U (0.50 U/kg). At 3 months, mean
      daily insulin requirements had increased to 39.2 U (0.52 U/kg), and
      glycohemoglobin improved to 9.4%. Most patients (78%) remained on insulin doses
      within 10% of the calculated requirements. All patients who were receiving more
      than 0.6 U/kg daily before assessment required a reduction in insulin dosage to
      improve glycemic control. CONCLUSION: Many patients with type 1 diabetes are
      receiving excessive insulin doses. An algorithm for intravenous administration of
      insulin may be useful for determining requirements and appropriate insulin doses
      for CSII pump therapy, especially in patients with poor glycemic control.

PMID- 15251741
TI  - Can follicle-stimulating hormone be used to define menopausal status?
AB  - OBJECTIVE: To assess the ability of the level of follicle-stimulating hormone
      (FSH) to distinguish among premenopausal, perimenopausal, and postmenopausal
      women. METHODS: We examined cross-sectional and longitudinal data from the second
      phase of the Massachusetts Women's Health Study (1986 to 1995), a population
      based cohort of 427 premenopausal and perimenopausal women identified from the
      first phase of the Massachusetts Women's Health Study (1981 to 1986). RESULTS:
      Boxplots of FSH levels throughout the menopausal transition displayed
      considerable overlap. Logistic regressions and their resulting receiver operating
      characteristic curves further demonstrated that, although FSH is a statistically
      significant predictor of menopausal status, no single value of FSH is expedient
      for distinguishing premenopausal from perimenopausal or perimenopausal from
      postmenopausal women. CONCLUSION: FSH alone is not an effective predictor of
      transition into the perimenopausal or postmenopausal period. Specifically, the
      frequently recommended FSH cutoff of 40 IU/L is inappropriate by itself for
      clinical determination of postmenopausal status.

PMID- 15251742
TI  - Thyrotoxic hypokalemic periodic paralysis: six cases in non-Asian patients.
AB  - OBJECTIVE: To describe six cases of thyrotoxic hypokalemic periodic paralysis
      (THPP) in non-Asian men. METHODS: We present six cases of THPP, including
      clinical and laboratory findings, treatment, and outcome, and review the related
      literature. RESULTS: Hypokalemic periodic paralysis is a relatively common
      occurrence in Asian men with thyrotoxicosis; however, it is unusual in non-Asian
      patients with thyrotoxicosis. Among our six patients--four Caucasians, one
      African-American, and one Hispanic--the precipitating factors, initial
      manifestations, and clinical course varied. In general, treatment with 131 I or
      potassium eliminated the paralytic episodes. CONCLUSION: THPP needs to be
      distinguished from nonthyrotoxic hypokalemic periodic paralysis. Although THPP is
      unusual in non-Asian men, it must be recognized because of the severe and
      potentially fatal complications, which are reversible with potassium replacement
      and antithyroid therapy.

PMID- 15251743
TI  - Triple oral antidiabetic therapy in type 2 diabetes mellitus.
AB  - To determine the effectiveness of triple oral antidiabetic therapy with a
      sulfonylurea, a biguanide, and a thiazolidinedione, we analyzed the results in 35
      patients who had previously had inadequate glycemic control with a combination of
      glimepiride and metformin. The study cohort consisted of 27 men and 8 women (mean
      age, 55.8 years) who had had type 2 diabetes mellitus for a mean duration of 8.7
      years. The addition of troglitazone (600 mg/day administered with the largest
      meal) to the glimepiride and metformin therapy yielded normal or near-normal
      glycemia in all 35 patients. Glycemic control was initially associated with mean
      weight gain; subsequently, however, mean weight was reduced to below the baseline
      level--perhaps attributable to the anorectic effect of metformin. Thus, for the
      first time, triple oral antidiabetic therapy with glimepiride, metformin, and
      troglitazone has been shown to be an efficacious therapeutic option for type 2
      diabetes.

PMID- 15251744
TI  - Sequential occurrence of toxic nodular goiter followed by Graves' disease.
AB  - OBJECTIVE: To present the first case of Graves' disease occurring after toxic
      nodular goiter in a patient who had not received radioiodine therapy. METHODS: We
      describe the clinical, laboratory, and radiologic findings in a 65-year-old woman
      with toxic nodular goiter followed by Graves' disease and review related reports
      in the literature. RESULTS: Although isolated case reports have documented the
      sequential occurrence of toxic nodular goiter or toxic adenoma and Graves'
      disease, no definite connection currently exists between these two types of
      hyperthyroidism. In cases previously described, Graves' disease appeared after
      the use of radioiodine for the treatment of the toxic nodular goiter. In our
      current patient, toxic nodular goiter was treated surgically, followed by the
      occurrence of Graves' disease 3 years later. CONCLUSION: This is the first
      published case of sequential toxic nodular goiter and Graves' disease in which
      radioiodine was not used for treatment of the goiter and thus cannot be
      implicated as the inciting event for the subsequent development of Graves'
      disease.

PMID- 15251745
TI  - Malignant thymic carcinoid in multiple endocrine neoplasia type I syndrome: case
      report and literature review.
AB  - OBJECTIVE: To describe a case of thymic carcinoid tumor in association with
      multiple endocrine neoplasia type I (MEN I) and discuss the various
      manifestations of this syndrome. METHODS: We present the clinical and laboratory
      data, including histopathologic and immunocytochemical findings, for our current
      patient and also review the literature on MEN I syndromes. RESULTS: In a 46-year
      old Caucasian man with no family history of multiple endocrine neoplasia,
      numerous MEN I lesions developed over time. The patient had gastrinoma of the
      duodenum, Zollinger-Ellison syndrome, hyperparathyroidism, a nonfunctioning
      adrenal mass, and foregut carcinoid tumors, including gastric and malignant
      thymic carcinoids. He sequentially underwent partial gastrectomy in conjunction
      with Billroth II anastomosis, a four-gland parathyroidectomy, and palliative
      radiotherapy for malignant carcinoid tumor, as well as endoscopic excision of
      accessible tumors. CONCLUSION: The involvement in MEN I can be clinically
      complex. Early detection of MEN I lesions will facilitate timely implementation
      of treatment and help minimize complications.

PMID- 15251746
TI  - Transient ionized hypocalcemia and secondary hyperparathyroidism accompanying
      acute adrenal insufficiency.
AB  - OBJECTIVE: To describe the hitherto unrecognized occurrence of transient ionized
      hypocalcemia with acute adrenal insufficiency and its therapy. METHODS: We
      present three case reports with documented longitudinal laboratory findings.
      RESULTS: Transient ionized hypocalcemia of acute illness has been noted in
      children and adults and is associated with increased mortality. Precipitating
      illnesses include gram-positive and gram-negative sepsis and staphylococcal toxic
      shock syndrome. We encountered three patients with transient ionized hypocalcemia
      associated with acute adrenal insufficiency. Similar to severely ill, transiently
      hypocalcemic patients without adrenal insufficiency, one patient demonstrated 25
      hydroxyvitamin D deficiency, a second had minimal magnesium deficiency, and a
      third had no identifiable underlying abnormality. All three patients exhibited a
      transient increase in levels of serum intact parathyroid hormone and 1,25
      dihydroxyvitamin D in response to ionized hypocalcemia, indicative of temporary
      secondary hyperparathyroidism. Two of the three patients were treated solely with
      glucocorticoids and intravenous administration of fluids, whereas the third
      received minimal intramuscularly administered magnesium and antibiotics in
      addition. All ultimately demonstrated a return to normal of serum total and
      ionized calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D with no further
      treatment, even though one patient remained deficient in 25-hydroxyvitamin D.
      CONCLUSION: On the basis of these cases, we conclude that acute adrenal
      insufficiency and its treatment must be added to the disorders associated with
      transient ionized hypocalcemia and that transient secondary hyperparathyroidism
      is characteristic of at least some of the patients.

PMID- 15251747
TI  - Ward's triangle bone mineral density determined by dual-energy x-ray
      absorptiometry is a sensitive indicator of osteoporosis.
AB  - OBJECTIVE: To assess the clinical utility of bone mineral density (BMD) of Ward's
      triangle by dual-energy absorptiometry (DEXA) as an indicator of osteoporosis in
      comparison with quantitative computed tomography (QCT) of the lumbar spine and
      DEXA of the lumbar spine and hip sites (trochanter and femoral neck). METHODS: We
      conducted a retrospective study of all patients (28 men and 17 women) with
      decreased BMD by QCT (T-score less than -1.0) who had DEXA BMD performed at the
      lumbar spine and hip between October 1993 and January 1995 in our Endocrine
      Clinic. RESULTS: Osteoporosis based on the World Health Organization criteria (T
      score less than -2.5) was defined by QCT lumbar spine BMD in 78% of the study
      subjects and by DEXA of Ward's triangle in 53%, of the femoral neck in 22%, of
      the trochanter in 7%, and of the lumbar spine in 2%. In the men, the only DEXA
      BMD measurement that was sensitive for detecting osteoporosis was Ward's
      triangle. Of the 24 men with osteoporosis by QCT BMD, 14 were defined as having
      osteoporosis by DEXA exclusively at Ward's triangle. The DEXA lumbar spine BMD
      measurement was actually above the mean for young normal control subjects in 8 of
      the 24 men with osteoporosis by QCT BMD. In the 11 women with osteoporosis by QCT
      BMD, the DEXA BMD at Ward's triangle and the femoral neck were equally sensitive
      in detecting osteoporosis, whereas the DEXA lumbar spine and trochanter BMD
      measurements were insensitive. CONCLUSION: DEXA BMD of Ward's triangle is a
      sensitive indicator of osteoporosis, particularly in men, and should be used to
      identify patients at increased risk for osteoporosis-related fractures.

PMID- 15251748
TI  - Effect of implanted insulin pumps on fluorescein transcapillary escape time in
      type 1 diabetes mellitus.
AB  - OBJECTIVE: To determine whether significant increases in fluorescein
      transcapillary escape time (FTET) would occur after treatment of patients with
      type 1 diabetes with insulin delivered intraperitoneally by a surgically
      implanted pump. METHODS: Nine patients with type 1 diabetes who were otherwise
      healthy and had received surgically implanted insulin pumps on a study protocol
      were recruited to have three measurements of FTET and glycosylated hemoglobin
      during an 18-month period. Serum fluorescein-albumin binding was measured at the
      time of the final test. Control FTETs were measured in 46 patients with type 1
      diabetes who did not have insulin pumps and in 15 adults without diabetes.
      RESULTS: In the implanted insulin pump group, 50% of the FTETs were below normal,
      but no significant longitudinal change in FTETs was noted in eight of the nine
      study patients. The mean FTETs in the implanted insulin pump group were
      significantly higher than those of the control patients with diabetes but without
      insulin pumps (mean, 88 versus 62 seconds; P<0.05) but significantly lower than
      those of the control subjects without diabetes (88 versus 163 seconds; P<0.001).
      Four of the nine patients with implanted insulin pumps had normal FTETs on all
      three studies. This subgroup had used insulin pumps (external + implanted) for
      significantly longer periods (6.2 versus 2.6 years; P<0.05) than the other five
      patients. These differences within the implanted pump group did not correlate
      with differences in glycosylated hemoglobin values or fluorescein-albumin
      binding; however, the glycosylated hemoglobin levels before insulin pump
      implantation were significantly lower than those of the other five patients.
      Three patients with onset of type 1 diabetes before age 10 years had the lowest
      FTETs. CONCLUSION: Implanted insulin pumps did not alter FTETs between 6 months
      and 32 months after pump implantation. Total time on insulin pumps (external and
      implanted) is associated with normal FTET, and onset of diabetes before age 10
      years is associated with abnormal FTET.

PMID- 15251749
TI  - Effect of major improvement in glycemic control on results of cardiovascular
      function tests in patients with insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effect of major improvement in glycemic control on
      cardiovascular function tests in patients with insulin-dependent diabetes
      mellitus (IDDM). METHODS: Eight men with chronic, poorly controlled IDDM (serum
      fructosamine >300 mmol/L and mean fasting blood glucose >200 mg/dL), who were 24
      +/- 6 years of age and had a mean duration of diabetes of 8 +/- 1 years, were
      studied. No patient had microalbuminuria, was taking medication other than
      insulin, or had evidence of heart disease. Patients underwent baseline continuous
      ambulatory blood pressure monitoring, echocardiographic studies, and
      cardiovascular autonomic function tests, which were repeated after 4 weeks of an
      intensified insulin treatment program (IITP), during which they reached and
      maintained blood glucose concentrations and serum fructosamine levels in near
      normal, nondiabetic ranges. RESULTS: Substantial changes in glycemic control had
      no significant influence on results of ambulatory blood pressure monitoring,
      cardiovascular autonomic function tests, and echocardiographic studies.
      CONCLUSION: Major improvement in glycemic control during a 1-month period in
      patients with IDDM had no significant influence on cardiovascular function tests.
      We cannot exclude the possibility that, after a longer duration of an IITP or in
      patients with clinically evident heart disease or evidence of major complications
      of diabetes, different responses might be observed.

PMID- 15251750
TI  - Improved glycemic control with use of oral hypoglycemic therapy with or without
      insulin.
AB  - OBJECTIVE: To determine whether combination oral hypoglycemic therapy in insulin
      using patients with non-insulin-dependent diabetes mellitus (NIDDM) can improve
      glycemic control for a prolonged period. METHODS: We expanded and extended an
      earlier study to include 130 patients with NIDDM for 10 to 30 years who had been
      using twice-daily mixed insulin for less than 10 years. Reduction and eventual
      elimination of the insulin therapy and substitution of metformin and a
      sulfonylurea were attempted. At follow-up visits, patients were weighed, random
      plasma glucose levels were determined, and glycosylated hemoglobin values were
      obtained. RESULTS: Of 130 C-peptide-positive patients with NIDDM receiving twice
      daily mixed insulin, 100 were successfully transferred to combination oral
      hypoglycemic therapy with glyburide originally and later glimepiride and
      metformin--a primary failure rate of 23.1%. Secondary failure occurred in 20
      patients after a mean duration of 6.4 months. Two patients with successful
      conversion to oral combination therapy resumed insulin treatment because of cost.
      Of the patients with primary failures, 6 had gastrointestinal side effects, 10
      were successfully managed on combination oral therapy plus evening mixed insulin,
      and 14 ultimately received twice-daily insulin and metformin. Of the secondary
      failures, 13 were controlled on combination oral therapy plus evening insulin and
      7 on twice-daily insulin in conjunction with metformin. No difference was found
      in the original C-peptide levels among these three groups. Glycosylated
      hemoglobin levels were significantly less on combined oral hypoglycemic therapy
      (9.8% versus 8.3%; P = 0.0001), on combination oral therapy plus evening insulin
      (11.2% versus 9.7%; P = 0.001), and on return to twice-daily mixed insulin with
      metformin (11.0% versus 9.9%; P = 0.04). Those eight patients who resumed twice
      daily insulin therapy alone, however, had a nonsignificant increase in
      glycosylated hemoglobin (9.3% versus 9.9%). CONCLUSION: Improvement in
      glycosylated hemoglobin level in insulin-using patients with NIDDM can be
      obtained with combination oral therapy alone, combination oral therapy with once
      daily evening insulin, or twice-daily mixed insulin with metformin in comparison
      with twice-daily insulin alone.

PMID- 15251751
TI  - Amiodarone-induced hyperthyroidism and a thyroid nodule.
AB  - OBJECTIVE: To report two cases of thyrotoxicosis associated with amiodarone
      therapy and to discuss how the presence of a thyroid nodule alters management.
      METHODS: We describe two patients with amiodarone-induced hyperthyroidism, review
      the mechanisms of disease, and outline a strategy for decision making relative to
      treatment in the presence of a thyroid nodule. RESULTS: Amiodarone-induced
      thyrotoxicosis occurs by two mechanisms: a direct toxic effect and iodine
      loading. This condition may be treated medically or surgically, but when
      discontinuation of amiodarone therapy is not possible and medical management is
      ineffective, surgical therapy is often necessary. The optimal presurgical
      management in the cases described required the use of thyroid scanning to
      determine whether the disease process was attributable to a hyperfunctioning
      nodule or generalized. The findings were helpful in planning the extent of
      surgical excision. CONCLUSION: When surgical treatment is planned for patients
      with a solitary thyroid nodule and amiodarone-induced hyperthyroidism,
      preoperative thyroid scanning will direct the surgeon to perform either subtotal
      thyroidectomy for diffuse disease or lobectomy for a hyperfunctioning nodule.

PMID- 15251752
TI  - An antineutrophil cytoplasmic autoantibody associated with a propylthiouracil
      induced adult respiratory distress-like syndrome: report of a case and review of
      the literature.
AB  - OBJECTIVE: To report the first case of propylthiouracil-induced adult respiratory
      distress-like syndrome associated with the presence of an antineutrophil
      cytoplasmic autoantibody. METHODS: We describe the initial manifestations,
      laboratory findings, and clinical course in a patient and discuss underlying
      factors potentially contributing to her condition. RESULTS: A 57-year-old woman
      with hyperthyroidism had an influenza-like illness and vasculitis during
      propylthiouracil therapy. Three days after she was admitted to the hospital, an
      adult respiratory distress-like syndrome developed. Results of perinuclear
      antineutrophil cytoplasmic antibody (pANCA) and antimyeloperoxidase antibody
      studies were positive. Her condition improved after the introduction of
      glucocorticoid therapy and the withdrawal of propylthiouracil treatment. The
      pANCA level, however, remained unchanged 3 months after her dismissal from the
      hospital. CONCLUSION: The propylthiouracil-induced adult respiratory distress
      like syndrome may be a hypersensitivity phenomenon, and the presence of the pANCA
      could be a marker of a common mechanism of injury that stimulates its production
      rather than a pathogenic factor responsible for vascular injury in our patient.

PMID- 15251753
TI  - Spontaneous hypoglycemia associated with congestive heart failure attributable to
      hyperinsulinism.
AB  - OBJECTIVE: To report a case of spontaneous hypoglycemia associated with
      congestive heart failure in an adult. METHODS: We describe a 72-year-old man in
      whom profound hypoglycemia (serum glucose level, 21 mg/dL) developed during an
      exacerbation of heart failure. Clinical and laboratory data are reviewed.
      RESULTS: An inverse relationship was found between both serum insulin and C
      peptide levels and serum glucose level. Serum glipizide and glyburide levels were
      undetectable, and no insulinoma was found on radiologic imaging. Hypoglycemia
      resolved after alleviation of the congestive heart failure. CONCLUSION: In this
      case, the hypoglycemia was attributed to hyperinsulinemia. Possible mechanisms
      include impaired insulin degradation and shunting of portal blood into the
      systemic circulation.

PMID- 15251754
TI  - Thyroid function during pregnancy and the postpartum period: iodine metabolism
      and disease states.
AB  - OBJECTIVE: To review various aspects of thyroid function during and early after
      pregnancy. METHODS: We discuss biochemical and potential pathologic changes in
      the thyroid associated with the gestational and postpartum periods. RESULTS:
      Urinary iodine excretion during the last trimester of gestation in healthy
      euthyroid women shows that, in areas with mild iodine intake, iodine
      supplementation is necessary during pregnancy and the postpartum period. This
      measure should be considered in iodine-sufficient areas as well. Thyroglobulin is
      the main biochemical marker of persistent thyroidal stimulation. Alterations in
      thyroid volume during pregnancy can persist after delivery, especially in breast
      feeding mothers. In most patients, the goitrogenic stimulus of pregnancy can be
      suppressed with iodine supplementation. Autoimmune thyroid disease during
      pregnancy and the postpartum period is reflected by monitoring of thyroid
      peroxidase antibodies (TPO-Ab). Women with positive test results for TPO-Ab early
      in gestation showed a highly significant decrease in free thyroxine and increased
      thyroid-stimulating hormone levels late in gestation. The main marker of Graves'
      disease during pregnancy is thyroid-stimulating antibodies. Nonautoimmune
      gestational hyperthyroidism differs from Graves' disease in that thyroid
      stimulating antibodies are not detectable. CONCLUSION: Clinicians should be alert
      to the fact that pregnancy can induce thyroidal pathologic conditions.

PMID- 15251755
TI  - Dehydroepiandrosterone supplements: bringing sense to sensational claims.
AB  - OBJECTIVE: To summarize the current information about dehydroepiandrosterone
      (DHEA), a steroid hormone produced in the adrenal cortex. METHODS: The
      biochemical and physiologic features of DHEA and its purported effects on overall
      age-related decline and on various disorders are reviewed. In addition, the
      potential side effects from administration of DHEA are discussed. RESULTS: During
      the normal life cycle, levels of DHEA fluctuate, beginning with production of
      large quantities in the fetus, stopping at birth, resuming during ages 5 to 7
      years, and increasing throughout puberty to maximal production in the 20s.
      Thereafter, DHEA levels progressively decline. This age-related decline in
      physiologic levels of DHEA has prompted speculation about a relationship between
      relative "DHEA deficiency" in older age and diseases of aging as well as the
      possibility of deriving benefits from administration of DHEA. Certain studies in
      animals (primarily rodents) have suggested anticancer effects of DHEA in
      pharmacologic doses and improvement in metabolism. In various studies in animals
      and humans, discrepant results have been found in the assessment of the
      association between DHEA levels and coronary artery disease. Likewise, the
      clinical significance of changes in immune function with DHEA treatment is
      unknown. Because DHEA is classified as a "nutritional supplement," it is not
      subjected to government regulation, and a potential exists for inaccurate dosage
      and impurities. CONCLUSION: Studies have shown that DHEA influences multiple
      systems and disease processes in animals and humans; some of these effects could
      be considered beneficial and others detrimental. To date, no long-term health
      benefits from DHEA in "replacement" doses have been demonstrated.

PMID- 15251756
TI  - Diabetes and atherosclerosis: mechanisms and management.
AB  - OBJECTIVE: To discuss the association of diabetes and atherosclerosis and outline
      various management options. METHODS: We reviewed the findings in pertinent
      studies in the literature. RESULTS: Atherosclerosis accounts for virtually 80% of
      all diabetes-related mortality. It is also a principal reason for hospitalization
      of patients with diabetes. Diabetes profoundly affects the pathogenesis of
      atherosclerosis through various mechanisms. Established cardiovascular risk
      factors are more prevalent in diabetic than in nondiabetic patients. Although
      trials of intensive glycemic control have been somewhat disappointing for
      decreasing atherogenesis, the results of trials with lipid-regulating therapies
      have been more encouraging. CONCLUSION: Atherogenesis is a multifactorial, multi
      stepped process. Although established risk factors do not entirely explain the
      increased risk of cardiovascular disease in patients with diabetes, they do seem
      to have a major role. Therefore, the management of patients with diabetes must
      address these contributing risk factors.

PMID- 15251757
TI  - Utilization of commercial laboratory results in management of hyperandrogenism in
      women.
AB  - OBJECTIVE: To compare results from testosterone radioimmunoassay kits commonly
      used by commercial laboratories as well as their reference ranges and to analyze
      the scientific literature for ranges of serum testosterone levels in normal women
      and those with hyperandrogenism. METHODS: We reviewed quality assurance reports
      of various testosterone ligand challenges from four groups of laboratories and
      summarized testosterone data from 17 published reports about normal women and 14
      studies of hyperandrogenic women. RESULTS: A significant variability was
      demonstrated between the radioimmunoassay kits at all concentrations (for
      example, a sample with a mean testosterone level of 96.1 ng/dL was reported by
      some laboratories as containing 71.8 ng/dL and by others as 123.4 ng/dL). All
      laboratories provide essentially the same "reference range" (approximately 10 to
      90 ng/dL) but do not report how the range was established. The scientific
      literature clearly shows a significant separation in serum testosterone levels
      between normal (that is, not hyperandrogenic) and hyperandrogenic women. Most
      hyperandrogenic women had testosterone levels >50 ng/dL, whereas most normal
      control subjects had levels <40 ng/dL. Thus, most of these women with
      hyperandrogenism would have been considered to have normal testosterone levels if
      the reference ranges of commercial laboratories were used. CONCLUSION: These data
      illustrate the difficulty that physicians face when they are required to use
      different commercial laboratories to measure serum testosterone levels. We
      propose that (1) reference ranges be established on a clinically defined
      population for each hormone and method used, (2) laboratory reports include
      information about method and reference range population, and (3) physicians be
      allowed to choose which laboratories are used for their patients' hormone
      determinations, for consistency of results.

PMID- 15251758
TI  - Use of iodine-123 as a diagnostic tracer for neck and whole-body scanning in
      patients with well-differentiated thyroid cancer.
AB  - OBJECTIVE: To determine whether 123 I can be used as a safe and effective
      alternative tracer to 131 I for imaging remnant tissue and for searching for
      metastatic lesions of well-differentiated thyroid cancer. METHODS: We studied a
      series of 16 patients (10 women and 6 men; 29 to 73 years of age) who had well
      differentiated thyroid cancer and had undergone thyroidectomy and subsequent
      radioiodine treatment. Diagnostic 10 mCi (either preablation or postablation)
      were compared with the 5- to 7-day 131 I posttherapy scans (doses, 75 to 200
      mCi). Scans were jointly interpreted by nuclear medicine and endocrinology staff
      members. RESULTS: Of the 16 patients, 15 had concordant findings between the 123
      I diagnostic images and the corresponding 131 I posttherapy scans. Only one
      patient had additional lesions noted on the posttherapy 131 I scan, which was
      attributed to the higher dose the patient received during radioiodine treatment
      (a 6% discordance rate). This discordance, however, would not have changed the
      patient treatment. No advantage was noted for delayed imaging at 48 hours; the 24
      hour images were satisfactory. The 123 I scans were of higher resolution than the
      131 I scans. CONCLUSION: Diagnostic 123 I scans are an acceptable alternative to
      131 I scanning for whole-body imaging in well-differentiated thyroid cancer and
      demonstrate adequate imaging of thyroid remnant tissue or metastatic lesions from
      thyroid carcinoma comparable to the post-therapy scans. 123 I scans also offer
      greater convenience to patients because they do not have to return for 48- or 72
      hour scans. Furthermore, they facilitate earlier institution of therapy by
      decreasing the interval between diagnostic scanning and radioiodine treatment.

PMID- 15251759
TI  - Androgen replacement in the treatment of Klinefelter's syndrome: efficacy and
      safety of a nonscrotal permeation-enhanced testosterone transdermal system.
AB  - OBJECTIVE: To report the efficacy and safety of a permeation-enhanced nonscrotal
      testosterone transdermal (TTD) system for the treatment of Klinefelter's
      syndrome. METHODS: Fifteen male patients with Klinefelter's syndrome, including
      12 patients who received previous intramuscular (IM) treatment with testosterone
      esters, were part of the study population from three phase III clinical studies;
      13 completed the studies. Patients applied two TTD systems nightly for 6 months
      or more. Nocturnal erections were assessed by RigiScan monitoring; sexual
      function was evaluated by using the Watts and Davidson questionnaires.
      Hypogonadal symptoms were determined by direct patient questioning. RESULTS: Mean
      morning serum testosterone levels increased to within normal range in all 13
      patients (from 5.9 +/- 3.2 nmol/L at hypogonadal baseline to 22.3 +/- 5.6 nmol/L
      at 6 months). Luteinizing hormone levels decreased to within normal range in six
      patients and showed clinically significant decreases in four of the other seven
      patients (from 25 +/- 12 IU/L at hypogonadal baseline to 17 +/- 11 IU/L at 6
      months). Nocturnal erections improved significantly during TTD system therapy in
      comparison with the hypogonadal state. Patient self-reported measures of sexual
      functioning were comparable to those during prior IM testosterone treatment and
      better than during the hypogonadal state. Hypogonadal symptoms decreased during
      TTD therapy in comparison with hypogonadal baseline. No clinically significant
      changes were noted in prostate volume, prostate-specific antigen, or lipid
      values. Three patients experienced anxiety or depression during TTD treatment,
      requiring discontinuation of therapy in one case and use of antidepressants in
      the other two. CONCLUSION: The testosterone patches were generally well tolerated
      in all patients. The nonscrotal TTD system for testosterone replacement is a safe
      and effective treatment for patients with Klinefelter's syndrome.

PMID- 15251760
TI  - Cessation of smoking rapidly decreases erectile dysfunction.
AB  - OBJECTIVE: To assess the relationship between cessation of smoking and rapid
      improvement in erectile capacity as well as the effect of nicotine patches on
      nocturnal penile tumescence and rigidity. METHODS: Nocturnal penile erections
      were studied in 10 smokers with use of the RigiScan portable home monitor. Two
      nights were monitored: for the first night, the patients had not stopped smoking;
      for the second night, the patients had stopped smoking for 24 hours. In addition,
      four men were monitored after cessation of smoking and wearing nicotine patches
      for 1 month. RESULTS: Multiple variables studied showed a statistically
      significant improvement in nocturnal penile tumescence and rigidity in the men
      who had stopped smoking for 24 hours. Continued improvement was noted in the four
      men who were monitored while not smoking and wearing nicotine patches for 1
      month. CONCLUSION: Stopping cigarette smoking is a factor that rapidly improves
      penile tumescence and rigidity. Because the improvement continues while the
      patient is receiving nicotine from transdermal patches, some factor or factors
      other than the nicotine are responsible for the erectile dysfunction.

PMID- 15251761
TI  - Influence of an interdisciplinary diabetes specialist team on short-term outcomes
      of diabetes at a community health center.
AB  - OBJECTIVE: To assess the effect on short-term diabetes outcomes of intervention
      with an interdisciplinary diabetes specialist team at a primary-care community
      health center in East Harlem, New York City. METHODS: An interdisciplinary
      diabetes specialist team, consisting of a diabetologist, a bicultural certified
      diabetes nurse-educator, and a nutritionist, attended weekly clinics at a primary
      care community health center in East Harlem. Emphasis was placed on communicating
      in the patient's primary language and providing nutritional counseling, diabetes
      education, and diabetes management. After 1 year, a retrospective review of
      medical records for patients seen by the diabetes team was performed to assess
      the influence of this intervention on performance of home glucose monitoring
      (HGM), frequency of hypoglycemia, and changes in diabetes treatment regimens. Of
      70 patients referred to the diabetes team by their primary-care providers, 50
      underwent follow-up for at least 6 months and were included in the statistical
      analysis. RESULTS: Of the 50 study patients, 94% had type 2 diabetes, with a mean
      duration of 11.2 years. Eighty-two percent were Hispanic, and 18% were Afro
      American. The mean age was 54.6 years. Microvascular complications were present
      in 44%, and macrovascular complications were present in 22%. HGM was done by 13
      patients (26%) before and 33 patients (66%) after diabetes team intervention
      (P<0.001). Before intervention by the diabetes team, 14 patients (28%) were
      having episodes of unrecognized hypoglycemia. Unrecognized hypoglycemia resolved
      after intervention in all but two patients with type 1 diabetes (P<0.001). Before
      intervention, diabetes treatment was dietary in 6 patients, a sulfonylurea in 19,
      and insulin in 25; after intervention, 5 patients had dietary management of their
      diabetes, 14 were taking a sulfonylurea, and 31 were receiving insulin (P<0.05).
      CONCLUSION: Providing access to an interdisciplinary diabetes specialist team at
      the site of primary care had a beneficial effect on short-term diabetes outcomes
      in inner-city Hispanic and Afro-American patients with diabetes. Providing
      specialty care in the primary-care setting may be one model for improving the
      quality and long-term outcomes of diabetes care, particularly in high-risk
      populations.

PMID- 15251762
TI  - A case of Noonan's syndrome with numerous cardiac abnormalities.
AB  - OBJECTIVE: To report a case of Noonan's syndrome in a patient with numerous
      cardiac abnormalities. METHODS: We present a case report of a patient with
      Noonan's syndrome, including clinical, laboratory, and radiologic findings, and
      discuss the characteristic features of this condition. RESULTS: A 19-year-old
      male patient had most of the typical clinical findings of Noonan's syndrome
      dysmorphic face, short stature, ear abnormalities, cryptorchidism, webbed neck,
      and high palate. In addition, mitral valve prolapse, secondary mitral
      insufficiency, left ventricular hypertrophy, and secondary tricuspid
      insufficiency were diagnosed. Although some cardiac abnormalities have been
      reported in patients with this syndrome, a case with numerous cardiac
      abnormalities has not been described previously. CONCLUSION: Noonan's syndrome is
      a rare disorder with characteristic clinical features and cardiac abnormalities.
      Although previously reported cases have described cardiovascular anomalies, on
      review of the literature we found no other case with numerous cardiac
      abnormalities.

PMID- 15251763
TI  - An ectopic adrenocorticotropic hormone syndrome caused by a sacrococcygeal
      chordoma: report of a case with a slow progression.
AB  - OBJECTIVE: To report the first case of an ectopic adrenocorticotropic hormone
      (ACTH) syndrome caused by a sacrococcygeal chordoma. METHODS: We present a case
      report with clinical, laboratory, and histologic details. RESULTS: A 76-year-old
      man was admitted to the hospital because of urinary obstruction. Five years
      previously, a urethral mass had been detected, and transurethral prostatectomy
      had been performed. Annual computed tomographic (CT) scans showed no change in
      size of the mass. In 1995, skin hyperpigmentation, central obesity, and bilateral
      edema were noted. The patient was admitted to the hospital in July 1996. A CT
      scan of the abdomen revealed a large mass close to the sacrum and compressing the
      bladder and rectum. Cortisol measurements (AM and PM) were 309 and 271 ng/mL,
      respectively. The plasma ACTH concentration was extremely elevated (3,125 pg/mL).
      Although resection of the mass was attempted, complete resection was not possible
      because the tumor had infiltrated the sacrum. Plasma cortisol concentrations in
      samples obtained 7 and 8 days postoperatively were normal. Plasma ACTH was
      substantially decreased (180 pg/mL) but remained above normal. The histologic
      features of the tumor were compatible with a chordoma. Neoplastic cells stained
      positively for ACTH. CONCLUSION: This report describes the first case of an
      ectopic ACTH syndrome caused by a sacrococcygeal chordoma. A slow progression of
      symptoms in an ectopic ACTH syndrome had been described only for carcinoid
      tumors. These data add a new entry to the list of neoplasms capable of causing
      this syndrome.

PMID- 15251764
TI  - Giant-cell granulomatous hypophysitis.
AB  - OBJECTIVE: To describe the clinical features of giant-cell granulomatous
      hypophysitis and to report on the results of corticosteroid treatment. METHODS: A
      case of giant-cell granulomatous hypophysitis is presented, and the pertinent
      literature is reviewed. RESULTS: A 41-year-old woman with anterior pituitary
      dysfunction had a pituitary mass that was 18 by 16 by 13 mm by magnetic resonance
      imaging. The pituitary stalk was thickened and enhanced after intravenous
      administration of gadolinium. A biopsy specimen that was obtained at
      transsphenoidal pituitary exploration revealed that the patient had giant-cell
      granulomatous hypophysitis, a rare inflammatory pituitary disorder. High-dose
      corticosteroid therapy failed to reverse her anterior pituitary dysfunction.
      CONCLUSION: The coincidence of a contrast-enhancing pituitary mass with a
      thickened pituitary stalk and the awareness of the rare occurrence of endocrine
      inactive tumors in women of childbearing age should suggest an inflammatory
      pituitary condition. Such lesions should also be suspected in otherwise healthy
      young women with hypopituitarism and no evidence of hormone hypersecretion. On
      the basis of the literature and our experience, corticosteroid treatment does not
      seem to improve anterior pituitary function.

PMID- 15251766
TI  - Obesity in the Paleolithic era? The Venus of Willendorf.

PMID- 15251765
TI  - Amiodarone and the thyroid.
AB  - OBJECTIVE: To review the amiodarone-associated alterations in thyroid hormone
      metabolism and thyroid function and compare them with the effects of inorganic
      iodide. To clarify the pathophysiologic features and treatment of amiodarone
      associated hypothyroidism and thyrotoxicosis. SUMMARY: Amiodarone, an iodinated
      benzofuran, is an important antianginal and antiarrhythmic medication. It also
      alters thyroid hormone metabolism and may precipitate hypothyroidism or
      hyperthyroidism. Amiodarone-associated hypothyroidism (AAH) is similar to iodine
      induced hypothyroidism. Amiodarone-associated thyrotoxicosis (AAT) has a complex
      pathophysiology. Type I AAT is due to increased thyroid hormone synthesis and
      release and occurs in patients with multinodular goiter or Graves' disease.
      Therapeutic interventions may include discontinuation of amiodarone, thionamide
      therapy, perchlorate, or surgery. In type II AAT, hyperthyroidism is the
      consequence of a destructive thyroiditis with release of preformed thyroid
      hormone. Prednisone therapy is the treatment of choice. The distinction between
      these two entities is of considerable clinical and therapeutic importance.

PMID- 15251767
TI  - The good and the bad of self-monitoring of blood glucose.

PMID- 15251768
TI  - Normal urinary growth hormone measurement in short-stature early pubertal boys
      may help to exclude growth hormone deficiency.
AB  - OBJECTIVE: To determine whether urinary growth hormone (U-GH) measurement is a
      useful indicator of subsequent growth rate in young boys. METHODS: We assessed
      the U-GH concentrations in five early pubertal boys with constitutional short
      stature (CSS) who were referred to a growth clinic and compared the results with
      those obtained in normal children and in children with GH deficiency. RESULTS: In
      the five early pubertal short-stature boys, the U-GH concentration ranged from
      3.7 to 9.7 ng/night and, despite their blunted plasma GH responses to two
      different pharmacologic tests (peak plasma GH <7 ng/mL), proved to be a useful
      indicator of their subsequent normal growth rate. The U-GH was 2.2 +/- 0.2 and
      4.1 +/- 0.5 ng/night in 38 normal prepubertal and pubertal children,
      respectively, 2.4 +/- 0.2 ng/night in 13 subjects with CSS, and 1.1 +/- 0.2
      ng/night in 16 GH-deficient short-stature children. CONCLUSION: We may speculate
      that 24-hour GH secretion and possibly U-GH normalize sooner than do responses to
      provocative testing as sex steroids appear in early pubertal constitutional short
      stature boys. From a practical standpoint, it seems that U-GH values higher than
      2.6 ng/night (mean + SE value for subjects with CSS) in such patients may justify
      postponement of the pharmacologic tests and waiting for growth during the
      subsequent year.

PMID- 15251769
TI  - Effect of premixed nph and regular insulin on glucose control and health-related
      quality of life in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To compare the effect of the addition of regular insulin as a premixed
      70/30 insulin to the treatment regimen of patients with type 2 diabetes who had
      used NPH insulin alone relative to overall glycemic control (postprandial blood
      glucose), patient satisfaction, and health-related quality of life. METHODS: We
      studied 90 patients with type 2 diabetes in a 10-week, randomized, double-blind,
      crossover trial involving 9 clinical investigators. Patients previously treated
      with NPH insulin alone were transferred to 30% regular insulin added to 70% NPH
      as a premixed insulin (70/30) administered twice daily. Patients in one sequence
      group received NPH insulin twice daily for 4 weeks followed by 70/30 insulin for
      4 weeks; in the second sequence group, the order was reversed. RESULTS: The
      magnitude of the 1.5- and 2-hour postprandial glucose excursion was reduced with
      70/30 insulin in comparison with NPH insulin, and patients treated with 70/30
      insulin experienced fewer hypoglycemic events than with NPH insulin. With regard
      to health-related quality of life, patients treated with 70/30 insulin rated
      their physical functioning as better; rated their ability to be spontaneous,
      follow the meal plan, and interact socially to be less difficult; and had less
      fear of hypoglycemia and perceived their diabetes to be better controlled than
      when treated with NPH insulin alone. CONCLUSION: In patients with type 2 diabetes
      mellitus, premixed 70/30 insulin improved postprandial glycemic control and
      health-related quality of life without increasing the frequency of hypoglycemic
      events and without any additional cost.

PMID- 15251770
TI  - Thyroid-stimulating antibody assay using a human thyrotropin receptor transfected
      cell line: relationship to clinical features of graves' disease.
AB  - OBJECTIVE: To evaluate a Chinese hamster ovary cell line transfected with the
      human thyrotropin (thyroid-stimulating hormone or TSH) receptor (CHO-TSHR) for
      its use in routine clinical testing and compare it with the currently used Fisher
      rat thyroid cell line (FRTL-5) relative to the cyclic adenosine monophosphate
      (cAMP) responses to thyroid-stimulating antibodies (TSAb). METHODS: We analyzed
      112 serum samples prospectively. TSAb were measured concurrently by both CHO-TSHR
      cells and FRTL-5 cells. In addition, thyrotropin-binding inhibitory
      immunoglobulin (TBII) was measured by a radioreceptor assay. Among the study
      subjects, 51 had active Graves' disease, 40 had other thyroid disease, and 21 had
      no thyroid disease. RESULTS: Of 51 patients with Graves' disease, 38 (74%) had
      positive results in both cell assays, 4 (8%) had negative results in both assays,
      and 9 (18%) had positive responses with CHO-TSHR cells but negative results with
      FRTL-5 cells. No patient had negative findings with CHO-TSHR cells and positive
      results by FRTL-5 cells. All 61 patients in the other two groups had negative
      results by both assays (diagnostic specificity = 100%). The diagnostic
      sensitivity and accuracy of TSAb activity by the two cell lines (CHO-TSHR versus
      FRTL-5) were 92.2% versus 74.5% and 96.4% versus 88.4%, respectively. A
      significant correlation was noted between the TSAb activities in active Graves'
      sera by the two assays (r = 0.58; P<0.0001); however, values by the CHO-TSHR
      method were significantly higher (P<0.003). TSAb activities determined with both
      cell lines were positively correlated with the 24-hour thyroidal 131 I uptake (r
      = 0.62 and P<0.0005 in CHO-TSHR cells; r = 0.41 and P<0.05 in FRTL-5 cells). The
      difference in TSAb activity between patients with ophthalmopathy and those
      without ophthalmopathy was statistically significant with both FRTL-5 (P<0.01)
      and CHO-TSHR (P = 0.05) assays. The correlation between the severity of eye
      disease and TSAb activities was significant only with the FRTL-5 assay (P =
      0.009) but not with the CHO-TSHR assay (P = 0.16). TSAb activity showed a
      significant positive correlation with serum thyroxine, triiodothyronine, and TBII
      by both cell assays. Neither cell line showed a significant correlation between
      TSAb activity and antimicrosomal antibody titer. CONCLUSION: The CHO-TSHR cell
      line is superior to the standard FRTL-5 cell line in the cAMP bioassay for TSAb
      with reference to diagnostic sensitivity and accuracy, correlation with disease
      activity, simplicity, and cost.

PMID- 15251772
TI  - Event-related brain potentials in patients with hypothyroidism.
AB  - OBJECTIVE: To evaluate the cognitive function of patients with hypothyroidism,
      based on long-latency auditory event-related potentials (ERPs). METHODS: We
      investigated alterations of P300 latency in patients with hypothyroidism before
      treatment and after restoration of euthyroidism. ERPs were elicited in 14
      untreated patients with hypothyroidism (mean age, 26.71 +/- 2.39 years) and in a
      group of 30 control subjects with comparable mean age, sex distribution, and
      educational level. ERP recordings were repeated at 1 and 6 months after
      attainment of euthyroidism. RESULTS: Untreated patients with hypothyroidism had
      longer P300 and N1 wave latencies in comparison with those in the control
      subjects (P = 0.003 and P = 0.018, respectively). The mean P300 latencies did not
      change significantly 1 month after restoration of euthyroidism. At 6 months after
      attainment of euthyroidism, however, the mean P300 latencies returned to normal
      values, similar to those in the control subjects. CONCLUSION: We conclude that
      P300 latencies are impaired in patients with hypothyroidism, which is indicative
      of cognitive dysfunction. These alterations, however, may be reversed 6 months
      after attainment of euthyroidism.

PMID- 15251771
TI  - Effect of adding a sulfonylurea in patients with non-insulin-dependent diabetes
      mellitus previously well controlled with insulin.
AB  - OBJECTIVE: To determine whether insulin-requiring patients with non-insulin
      dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in
      weight control, serum lipid concentrations, or blood pressure from a reduction in
      exogenous insulin treatment. METHODS: Eighteen patients with well-controlled
      NIDDM who required insulin therapy were entered into a randomized, placebo
      controlled, double-blind, crossover study of the addition for 12 weeks of
      treatment with a second-generation sulfonylurea agent (micronized glyburide).
      RESULTS: The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at
      the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and
      7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the
      study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with
      active drug). Addition of the orally administered agent resulted in a 29%
      decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary
      C-peptide excretion. Patients had no change in weight after 12 weeks of either
      placebo or active drug. Plasma cholesterol levels declined slightly during the
      study, but they did not differ significantly during drug and placebo treatment.
      Blood pressure was unchanged in both the subjects with and without hypertension.
      CONCLUSION: In patients with NIDDM and good glycemic control with insulin
      treatment, a glyburide-related increase in endogenous insulin secretion caused a
      proportionate decrease in exogenous insulin requirements. With continued good
      glycemic control, however, the orally administered agent showed no additional
      benefit on weight, blood pressure, plasma triglycerides, or low-density
      lipoprotein or high-density lipoprotein cholesterol.

PMID- 15251773
TI  - A possible pre-zollinger-ellison state: report on a novel lesion.
AB  - OBJECTIVE: To describe a patient with a potential harbinger of Zollinger-Ellison
      syndrome. METHODS: We present a case of a 29-year-old woman with persistent
      galactorrhea and gastric distress, who was a member of an extensive multiple
      endocrine neoplasia (MEN) I kindred. Both clinical and laboratory findings are
      reviewed. RESULTS: Laboratory studies were notable for persistent hypercalcemia
      and increased levels of parathyroid hormone and fasting pancreatic polypeptide.
      Because of nonspecific upper gastrointestinal distress, which was sometimes
      responsive to antacids, the patient underwent further diagnostic evaluation.
      Baseline gastrin levels were normal. A secretin challenge test yielded normal
      results. At upper endoscopy, visual findings in the stomach and duodenum were
      unremarkable. A raised nodule (4 by 2 by 2 mm) was removed from an otherwise
      normal-appearing duodenum as a routine biopsy procedure. The acinar architecture,
      the inconspicuous nucleoli, and the granular, eosinophilic cytoplasm of the cells
      were diagnostic of a neuroendocrine tumor. Histologic immunohistochemical
      staining was positive for gastrin but negative for pancreatic polypeptide. RNA
      studies were not technically possible. Subsequently, serum pancreatic polypeptide
      levels normalized. The patient ultimately had hyperplastic parathyroid glands
      resected. CONCLUSION: The duodenal lesion may be a very early gastrinoma, a
      preclinical manifestation of the Zollinger-Ellison syndrome. The role of early
      resection of such lesions remains to be determined.

PMID- 15251774
TI  - Hypercalcemia due to subacute thyroiditis.
AB  - OBJECTIVE: To describe a patient who had hypercalcemia attributable to subacute
      thyroiditis. METHODS: A case history, including detailed results of laboratory
      tests, is presented, and the findings are discussed. RESULTS: A young woman with
      neck pain and fever was found to have increased free thyroxine and
      triiodothyronine levels but a decreased thyrotropin value. Concurrently, the
      serum calcium concentration was increased. Subacute thyroiditis was diagnosed.
      Within 1 month, the free thyroxine and serum calcium levels were normal.
      CONCLUSION: Thyrotoxicosis is a known cause of hypercalcemia. All previously
      reported cases of hypercalcemia due to hyperthyroidism involved Graves' disease,
      toxic multinodular goiter, or a toxic adenoma as the cause of the
      hyperthyroidism. The current case shows that short-term subacute thyroiditis can
      cause hypercalcemia.

PMID- 15251775
TI  - Metformin: mechanisms of antihyperglycemic action, other pharmacodynamic
      properties, and safety perspectives.
AB  - OBJECTIVE: To characterize the mechanisms of action of metformin and describe its
      effects and safety profile. METHODS: Results of more than 30 years of clinical
      use in countries other than the United States are summarized. In addition, the
      pharmacologic properties of metformin are compared with those of other
      antihyperglycemic agents. RESULTS: Approximately 90% of all cases of diabetes are
      non-insulin-dependent diabetes mellitus (NIDDM)--a heterogeneous disease that
      involves several pathogenic factors and is associated with other coexisting
      conditions, such as cardiovascular disease, hypertension, and obesity. Thus, an
      agent that controls blood glucose levels and has favorable effects on the
      concomitant conditions should be considered when pharmacologic intervention is
      needed for the treatment of NIDDM. Metformin possesses the pharmacodynamic
      properties to do both. Its mechanisms of action include the reduction of hepatic
      glucose production and enhancement of peripheral glucose disposal, making
      metformin an effective antihyperglycemic agent. It also has other pharmacologic
      properties, independent of its glycemic effects, that offer additional clinical
      benefits in comparison with other pharmacologic NIDDM treatments. These benefits
      include stabilization or even loss of weight in patients for whom weight gain is
      a concern and reduction of plasma lipid levels in patients with hyperlipidemia.
      CONCLUSION: On the basis of 3 decades of clinical experience, metformin has been
      shown to be not only a well tolerated but also a highly effective
      antihyperglycemic agent.

PMID- 15251776
TI  - New advances in insulin treatment of diabetes: overcoming barriers.
AB  - OBJECTIVE: To discuss the optimal role of insulin in the treatment of patients
      with diabetes mellitus. METHODS: We review the complications of diabetes,
      highlight the attempts to improve control of plasma glucose, and summarize
      current recommendations for use of insulin in clinical practice. RESULTS: With
      the strict new guidelines for the diagnosis of diabetes issued by the American
      Diabetes Association in July 1997--a plasma glucose level of 126 mg/dL (7 mmol/L)
      rather than 140 mg/dL (7.8 mmol/L)--an additional 8 million persons will be
      diagnosed this year, and diabetes and its complications will be at the forefront
      of public health concerns. Strong evidence indicates that with reduction of
      plasma glucose levels and tight control of glycohemoglobin, the rate of
      complications can be considerably decreased. Although insulin replacement therapy
      is well known to be both the best and the most cost-effective way to control
      glucose levels in patients with type 1 diabetes, studies have no shown that those
      with type 2 diabetes can likewise benefit from appropriate insulin therapy. Other
      investigations have indicated that coronary events are as likely to occur in
      patients with recently discovered impaired glucose tolerance as in patients with
      known diabetes (at a 2-hour postprandial glucose threshold of 96 mg/dL [5.3
      mmol/L]). Such finding suggest that there may be no such thing as "borderline
      diabetes" and give impetus to the search for improved types of insulin to treat
      all patients with diabetes. A recent candidate is the new insulin analogue
      lispro, which was developed by recombinant DNA techniques, with its design
      influenced by the structural analogy to another endogenous hormone, insulin-like
      growth factor I. Lispro is a fast-acting, rapidly dissipating insulin
      formulation. This profile allows lispro to be given less than 15 minutes before a
      meal, yet with little risk of postprandial hypoglycemia because its high mealtime
      peak is followed by rapid disappearance from the bloodstream. CONCLUSION: Lispro
      has been shown to improve postprandial control of plasma glucose and to decrease
      the occurrence of hypoglycemia episodes in comparison with regular insulin.
      Because of its stability and pharmacokinetic properties, lispro can also be used
      in insulin pump therapy.

PMID- 15251777
TI  - The case of urinary growth hormone.

PMID- 15251778
TI  - Combination therapy for type 2 diabetes.

PMID- 15251779
TI  - Long-term pharmacologic treatment of morbid obesity in a community practice.
AB  - OBJECTIVE: To determine the safety, efficacy, and metabolic changes in patients
      with morbid obesity treated with d,l-fenfluramine and phentermine in an open
      label trial. METHODS: In patients with a body mass index (BMI) =40.0 kg/m 2 (N =
      298) who sought assistance at a private medical practice for treatment of
      obesity, 60 mg of d,l-fenfluramine and 15 to 30 mg of phentermine resin were
      administered daily in an open-label trial, without placebo controls, for up to 24
      months. The setting was a community-based private practice. Study subjects were
      given instructions for a 1,200 to 1,400 kcal/day diet, exercise, and behavior
      modification. Follow-up included a monthly medical visit, behavior modification
      group attendance, quarterly laboratory evaluation, and electrocardiographic
      monitoring. RESULTS: BMI decreased from 45.8 kg/m2 to 37.4 kg/m2 (P<0.0001) in
      those who completed 12 months of treatment and to 38.2 kg/m2 (P<0.0001) in those
      who continued the protocol for 24 months. Statistically significant decreases in
      fasting blood glucose, total and high-density lipoprotein cholesterol,
      triglycerides, systolic and diastolic blood pressures, and fasting insulin
      concentrations were noted. The dropout rate was 42.3% at 12 months and 69.8% at
      24 months. The most common reason given for discontinuing participation in the
      study was "success" with the program (mean BMI loss of 7.8 kg/m2). Five patients
      discontinued treatment because of side effects. No laboratory or
      electrocardiographic abnormalities were noted that could be attributed to the
      medications. No statistically significant regain of weight occurred in those who
      completed 12 or 24 months of treatment. CONCLUSION: In this study, treatment of
      morbid obesity with d,l-fenfluramine and phentermine was safe and efficacious in
      promoting and maintaining weight loss. Moreover, statistically significant
      changes were noted in metabolic variables associated with risk of heart disease.
      Future efforts must focus on methods to improve long-term compliance.

PMID- 15251780
TI  - Lipoprotein(a) in patients who have non-insulin-dependent diabetes with and
      without coronary artery disease.
AB  - OBJECTIVE: To determine whether the level of lipoprotein(a) [Lp(a)] contributes
      to an increased risk of coronary artery disease (CAD) in patients with non
      insulin-dependent diabetes mellitus (NIDDM). METHODS: We prospectively evaluated
      established cardiovascular risk factors, metabolic control, and Lp(a) levels in
      53 men with NIDDM and CAD and compared these variables in 42 male patients with
      NIDDM but without CAD. RESULTS: The groups were comparable for age, diabetes
      control, treatment and duration of diabetes, obesity, and other cardiac risk
      factors. Lp(a) levels did not differ between the groups (12.2 versus 12.4 mg/dL
      in those with and without CAD, respectively) and were unrelated to age, duration
      of diabetes, diabetes control, obesity, smoking, hypertension, urinary albumin,
      cholesterol, triglycerides, or high-density lipoprotein cholesterol. Patients
      with retinopathy had a higher Lp(a) concentration than did those without
      retinopathy (24.9 +/- 6.0 versus 10.1 +/- 1.5 mg/dL; P = 0.01). A significant
      correlation existed between Lp(a) and low-density lipoprotein cholesterol
      concentrations (P = 0.01). CONCLUSION: Routine measurement of Lp(a) level in
      patients with NIDDM does not seem warranted because no association was found
      between Lp(a) concentration and CAD in this study population.

PMID- 15251781
TI  - Frequency of severe hypoglycemia in patients with non-insulin-dependent diabetes
      mellitus treated with sulfonylureas or insulin.
AB  - OBJECTIVE: To assess the frequency of severe hypoglycemia in patients with non
      insulin-dependent diabetes mellitus (NIDDM). METHODS: We surveyed a single
      diabetologist's clinical practice of consecutive patients with NIDDM during a 3
      month period. RESULTS: Of the 262 study participants interviewed, 172 insulin
      using and 90 sulfonylurea-using patients were asked whether they had ever had
      hypoglycemia severe enough to require the assistance of another person. Of the 90
      sulfonylurea-treated patients with NIDDM, 3 (3.3%) reported experiencing severe
      hypoglycemia on one occasion only. Of the 172 insulin-utilizing patients, 13
      (7.6%) had had severe hypoglycemic episodes--8 on one occasion only (5 of these
      had been iatrogenic circumstances and 3 had been precipitated by exercise or lack
      of food). Five insulin-requiring patients reported multiple bouts of severe
      hypoglycemia. With one exception, all patients were thin, and C peptide levels
      were low or undetectable. CONCLUSION: On the basis of this study, we conclude
      that severe hypoglycemia is extremely uncommon in NIDDM. When it occurs, it is
      usually accidental and seldom recurs. Patients with multiple bouts of severe
      hypoglycemia have almost complete insulin deficiency. Thus, aggressive treatment
      of NIDDM to avoid diabetic complications is rarely associated with severe
      hypoglycemia and is usually well tolerated.

PMID- 15251782
TI  - Serum thyrotropin determinations: comparison of second- and third-generation
      assays.
AB  - OBJECTIVE: To compare thyrotropin (thyroid-stimulating hormone or TSH) levels
      determined by second- and third-generation assays in sera extracted from blood
      samples withdrawn randomly from 34 subjects attending outpatient clinics.
      METHODS: Serum specimens were separated into two fractions and were frozen and
      stored at -20 degrees C for subsequent determination of TSH concentrations by
      second-and third-generation assays. The results were analyzed statistically.
      RESULTS: Of the 34 serum samples, 23 TSH levels were within normal ranges on both
      assays, whereas 9 samples showed subnormal TSH concentrations with both second-
      and third-generation assays. The other two samples revealed mildly increased TSH
      levels by the third-generation assay but high normal levels with the second
      generation assay. Moreover, mean TSH values determined with second- and third
      generation assays for all 34 serum samples were not significantly different (1.48
      versus 1.66 mU/L; P>0.05). Finally, a highly significant correlation (r = 0.987)
      was also noted between the two assays on simple linear regression. CONCLUSION:
      Thus, serum TSH determinations by both the second- and third-generation assays
      are almost identical, and attempting to achieve greater sensitivity to detect
      lower levels by further modifications in third-, fourth-, and even later
      generation assays may be an expensive and fruitless endeavor because of the
      inability of these methods to discern the thyroid functional state any better
      than the second-generation assay.

PMID- 15251783
TI  - Diffuse sclerosing variant of papillary thyroid carcinoma: case report and review
      of the literature.
AB  - OBJECTIVE: To describe a patient with a diffuse sclerosing variant of papillary
      (DSVP) thyroid cancer and to summarize the reported clinical manifestations and
      treatment of other patients with this malignant tumor. METHODS: We reviewed the
      pathologic findings in a 14-year-old girl, who had survived for 19 years after
      treatment of a presumed undifferentiated thyroid cancer. When reassessment
      revealed histologic features of DSVP cancer, we reviewed the case reports of this
      type of malignant lesion identified from a MEDLINE search of articles published
      between 1985 and 1995. RESULTS: Review of the pathologic features showed a
      diffuse tumor in the thyroid gland without an identifiable mass and extensive
      bilateral lymph node metastatic lesions. Histologic examination disclosed
      pronounced fibrosis, numerous psammoma bodies, primarily a solid growth pattern,
      lymphocytic infiltration, and extensive invasion of lymphatic spaces. The nuclear
      features were characteristic of papillary carcinoma. Review of 63 cases of DSVP
      cancer indicated that this variant accounted for 0.2 to 5.7% of papillary cancer,
      affected primarily young women, and usually manifested with diffuse involvement
      of one or both thyroid lobes. Thyroid antibodies were frequently detected in the
      serum. Cervical lymph node metastatic lesions, local invasion, and distant
      metastatic involvement were described in 75, 35, and 16% of patients,
      respectively. Although the cancer recurred in 37% of patients, only two died of
      this malignant tumor. CONCLUSION: DSVP cancer can be confused with nontoxic
      goiter, chronic thyroiditis, nonthyroidal malignant tumors, or undifferentiated
      thyroid cancer. We suggest that the same therapy used for young patients with
      conventional papillary thyroid cancer is also appropriate for most patients with
      the diffuse sclerosing variant.

PMID- 15251784
TI  - Misleading acute hypercalcemia due to hyperlipidemia: a method-dependent error.
AB  - OBJECTIVE: To report a case of artifactual hypercalcemia in a patient with
      hyperlipidemia. METHODS: We present clinical data and laboratory findings in a 33
      year-old woman with generalized fatigue, a recent 5-kg weight loss, and a papular
      rash on the extremities as well as a history of diabetes and hypertension.
      RESULTS: Physical examination revealed an obese patient with eruptive xanthomas
      and lipemia retinalis. Laboratory tests showed hyperlipidemia, hypercalcemia
      (serum calcium measured by spectrophotometry), anemia, hyperproteinemia,
      hyperuricemia, and hyperbilirubinemia. After 4 days of a low-fat, low-cholesterol
      diet and gemfibrozil therapy, the serum triglyceride level decreased, and the
      serum calcium concentration returned to normal. CONCLUSION: In patients with
      hypercalcemia without an obvious cause, a spurious measurement should be
      considered.

PMID- 15251785
TI  - Silent corticotroph adenoma: case report and literature review.
AB  - OBJECTIVE: To review the initial clinical manifestations and diagnosis of silent
      corticotroph adenoma. METHODS: We report a case and summarize the relevant
      literature. RESULTS: A 52-year-old patient with hypopituitarism underwent
      resection of a silent corticotroph adenoma. A circulating species was detected
      postoperatively, reactive in a highly sensitive adrenocorticotropic hormone
      (ACTH) 1-39 immunoradiometric assay (IRMA) and beta-endorphin or beta-lipotropin
      radioimmunoassay. The basal morning cortisol concentration consistently was <10
      microg/dL. Dynamic testing was performed to screen for Addison's disease,
      congenital adrenal hyperplasia, and Cushing's syndrome. During dexamethasone
      suppression, the molar concentration of circulating ACTH precursors by a two-site
      IRMA was 55-fold greater than the concentration of ACTH 1-39 by IRMA. We
      concluded that the tumor displayed impaired processing of pro-opiomelanocortin
      (POMC) and secreted a bioinactive POMC-derived peptide that was reactive in the
      ACTH 1-39 IRMA. CONCLUSION: Patients with silent corticotroph adenoma do not have
      clinically evident Cushing's syndrome. In some cases, bioinactive ACTH precursors
      may be detected by a sensitive ACTH 1-39 IRMA.

PMID- 15251786
TI  - Non-Hodgkin's lymphoma of the thyroid gland occurring after treated Hodgkin's
      lymphoma.
AB  - OBJECTIVE: To present a case report of the occurrence of non-Hodgkin's lymphoma
      in the thyroid gland of a patient who had previously undergone successful
      treatment of Hodgkin's lymphoma. METHODS: We describe pertinent historical
      features and current symptoms and laboratory findings in a 62-year-old man who
      had had successful treatment of Hodgkin's lymphoma 10 years previously and had
      been free of disease for a decade. We also review the related medical literature
      on the course of patients after therapy for Hodgkin's lymphoma. RESULTS: Because
      of a progressively enlarging anterior neck mass, hoarseness, and difficulty with
      breathing, a patient sought medical attention. Ten years previously, he had
      undergone irradiation and splenectomy for treatment of Hodgkin's lymphoma. In the
      current assessment, fine-needle aspiration and open biopsy yielded the diagnosis
      of non-Hodgkin's lymphoma, for which the patient received irradiation and
      chemotherapy. Review of the literature pertaining to diseases after treated
      Hodgkin's lymphoma, including second cancers, failed to identify any such prior
      reported case. CONCLUSION: Because the clinical profile of our patient was
      consistent with primary non-Hodgkin's lymphoma of the thyroid gland developing
      after radiation-treated Hodgkin's lymphoma, we conclude that this represents the
      first such reported example.

PMID- 15251787
TI  - New therapeutic approaches to non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To review the new treatment strategies for non-insulin-dependent
      diabetes mellitus (NIDDM). METHODS: Various measures aimed at either increasing
      insulin secretion or decreasing insulin resistance are outlined. In addition, the
      management of obesity in patients with diabetes is discussed. RESULTS: Two new
      sulfonylureas being investigated are repaglinide, which has a rapid onset of
      action, rapid reversal, and potential usefulness as a preprandial treatment of
      NIDDM, and glimepiride, the most potent sulfonylurea on a weight basis with an
      efficacy similar to that for glyburide. Metformin, an orally administered
      biguanide hypoglycemic agent, decreases blood glucose levels by 50 to 100 mg/dL
      and consistently improves triglyceride levels. Another agent for NIDDM therapy is
      acarbose, an a-glucosidase inhibitor. This agent avidly binds to intestinal
      disaccharidases and limits the postprandial increase in blood glucose.
      Troglitazone, a member of the thiazolidinedione class of insulin sensitizers,
      enhances insulin action and lowers blood glucose and blood pressure levels. In
      overweight patients with diabetes, fenfluramine has been the most effective
      centrally acting weight reduction agent. CONCLUSION: Management of patients with
      NIDDM has become more complicated because of the increased variety of therapeutic
      options available. In each patient, nonpharmacologic treatment as well as lipid
      lowering, blood pressure-lowering, and glucose-lowering agents must be
      considered.

PMID- 15251789
TI  - Morbid obesity: the price of progress.

PMID- 15251788
TI  - Prevalence of coronary artery disease risk factors in workers at the general
      hospital of Mexico of the ministry of health.
AB  - OBJECTIVE: To assess the prevalence of coronary risk factors in 2,463 health-care
      workers at the General Hospital of Mexico. METHODS: The study participants--1,620
      women (65.8%) and 843 men (34.2%)--ranged in age from 16 to 65 years old. Study
      subjects were classified into five occupational subgroups: maintenance workers,
      477 (19.4%); administrators, 697 (28.3%); physicians, 495 (20.1%); nursing staff,
      559 (22.7%); and students, 235 (9.5%). For each participant, a clinical history
      was elicited, anthropometric determinations were done, and samples were obtained
      for determining blood glucose, total cholesterol, low-density lipoprotein, high
      density lipoprotein, and triglyceride levels. RESULTS: Cholesterol levels above
      6.2 mmol/L (>240 mg/dL) were found in 14.9% of the women and 14.8% of the men in
      the overall study group. Triglyceride levels of more than 2.25 mmol/L (>200
      mg/dL) were found in 471 participants (19.1%). The prevalence of obesity was
      13.5%, and high blood pressure was detected in 22.2% of study participants. Only
      32.2% of subjects engaged in physical exercise one or more times per week;
      moreover, 32% of those surveyed smoked. The prevalence for diabetes mellitus was
      6.25%. The multifactorial coronary risk index was high in 13.2% of men and 43.2%
      of women older than 30 years of age. CONCLUSION: This study confirmed the high
      prevalence of risk factors for cardiovascular diseases in personnel of the
      General Hospital of Mexico. Because many of these risk factors are modifiable,
      educational efforts and preventive measures should be implemented.

PMID- 15251790
TI  - Lipoprotein(a) and diabetes mellitus.

PMID- 15251791
TI  - Bone mineral density, sex hormones, and long-term use of neuroleptic agents in
      men.
AB  - OBJECTIVE: To study the prevalence and severity of bone mineral loss and its
      relationship to sex hormone levels in men on long-term neuroleptic therapy.
      METHODS: Sixteen men with schizophrenia who were from 19 to 62 years old and had
      taken neuroleptic medication for 1 to 30 years had bone mineral density (BMD) of
      the lumbar spine and proximal femur measured by dual-energy x-ray absorptiometry.
      Results were compared with those from 16 age-matched control subjects. Serum
      testosterone, sex hormone-binding globulin, free testosterone index (FTI),
      prolactin, and pituitary gonadotropins were assayed and compared with age-matched
      Red Cross blood donor controls (N = 23 to 90 for the various assays). RESULTS: At
      the lumbar spine and at two of the three sites in the proximal femur (trochanter
      and Ward's triangle but not femoral neck), the BMD was lower in patients than in
      controls. A statistically significant increase in prolactin and sex hormone
      binding globulin and a significantly decreased luteinizing hormone and FTI were
      found in the treated versus the control group. In the patient group, a
      significant inverse relationship existed between age and BMD at all sites. Lumbar
      spine density was related directly to FTI (r = 0.607; P=0.05) and inversely to
      duration of treatment (r = -0.767; P<0.001), although both correlations were
      accounted for mainly by age associations in multiple stepwise linear regression.
      Prolactin values did not correlate with either BMD or FTI. CONCLUSION: BMD was
      significantly lower with long-term neuroleptic use. In the lumbar spine, these
      changes may be related to the associated findings of decreased free testosterone
      and hyperprolactinemia, although the significance of other factors such as an
      independent drug effect, the psychiatric disease itself, and lifestyle cannot be
      excluded.

PMID- 15251792
TI  - Intravenously administered pamidronate for treating refractory Paget's disease of
      bone.
AB  - OBJECTIVE: To report our experience with the use of intravenously administered
      pamidronate in 16 patients with refractory Paget's disease of bone. METHODS: We
      describe our treatment regimen and outline serum alkaline phosphatase levels at
      baseline and after pamidronate therapy in our study cohort. In addition, we
      summarize clinical symptoms and response to treatment. RESULTS: Although clinical
      experience with pamidronate in the treatment of Paget's disease of bone has been
      limited in the United States, elsewhere it has been shown to be an effective
      agent that inhibits the increased osteoclastic activity characteristic of this
      disease. Accordingly, in 16 patients with Paget's disease unresponsive to various
      other therapies, we administered pamidronate intravenously at a dose of 30 mg in
      500 mL of 5% dextrose in water during a 4-hour period once weekly for 6 weeks.
      Serum alkaline phosphatase was determined at baseline and at regular intervals
      for at least 12 months after the onset of therapy. Many of these patients
      reported relief of pain and an increased flexibility or range of motion after
      treatment. The only adverse effect reported by these patients was an acute-phase
      reaction during the first infusion in two patients. In all patients, serum
      alkaline phosphatase levels declined, and significant (P = 0.0012) decreases from
      baseline were noted within 6 weeks after the initial infusion. Maximal responses
      were generally seen within 6 months after treatment, serum alkaline phosphatase
      levels decreasing as much as 91% from baseline. CONCLUSION: These data suggest
      that intravenous pamidronate therapy is an effective alternative to calcitonin
      and etidronate in the treatment of Paget's disease of bone, particularly in those
      patients refractory to such agents.

PMID- 15251793
TI  - Short-term effects of coronary angiographic contrast agents on thyroid function.
AB  - OBJECTIVE: To determine the effect of two iodine-containing contrast agents used
      for coronary angiography on subsequent thyroid hormone concentrations. METHODS:
      We prospectively studied thyroid function in 56 patients, with no previous
      history of thyroid disease and normal findings on thyroid examinations, who
      underwent nonemergent cardiac catheterization. Thyroid hormone concentrations
      were assessed at baseline and at day 1 and day 7 after administration of a
      radiographic iodinated contrast agent (Renografin or Omnipaque). RESULTS: Use of
      Omnipaque and Renografin was not associated with significant changes in thyroid
      stimulating hormone, total thyroxine, triiodothyronine resin uptake, free
      thyroxine index, or total triiodothyronine. Three patients had slightly increased
      thyroid-stimulating hormone concentrations at 7 days after angiography.
      CONCLUSION: Administration of iodinated contrast agents for cardiac
      catheterization does not result in hyperthyroidism in patients with previously
      normal findings on thyroid examination.

PMID- 15251794
TI  - Effect of desuppression on nodular thyroid disease.
AB  - OBJECTIVE: To ascertain the clinical effect of discontinuation of thyroxine (T4)
      suppression therapy in patients with solitary thyroid nodules or multinodular
      goiters (MNGs). METHODS: After long-term T4 suppression therapy was discontinued
      (desuppression) in 63 patients (45 with solitary or dominant nodules and 18 with
      MNGs), we conducted a prospective follow-up for a mean of 18 months in an effort
      to detect any thyroid-related changes. RESULTS: A dominant nodule developed in 4
      of 18 patients with MNGs. Fine-needle aspirations showed benign lesions in these
      four patients, but two were referred for thyroidectomy because of substantial
      nodule growth (both lesions proved to be benign). Of the 45 patients with
      solitary or dominant thyroid nodules, 4 were lost to follow-up, and 9 had
      clinically significant nodule enlargement and underwent thyroidectomy. One
      patient had clinically significant papillary carcinoma, and one had microscopic
      papillary carcinoma. CONCLUSION: These data on effect of discontinuation of T4
      suppression therapy suggest that (1) about 20% of patients with MNGs will
      ultimately have thyroid nodule enlargement and (2) about 20% of patients with a
      solitary or dominant nodule will have nodule enlargement, of which approximately
      20% will have papillary carcinoma.

PMID- 15251795
TI  - Ultrasonographic and Doppler study of the thyroid gland in Graves' disease before
      and after treatment with antithyroid drugs.
AB  - OBJECTIVE: To determine the effects of medical treatment on the thyroid gland,
      peripheral circulation, and laboratory findings in patients with Graves' disease.
      METHODS: Twenty patients with Graves' disease were treated with either
      carbimazole and propranolol (group I) or carbimazole only (group II). Serum free
      thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyrotropin-binding
      inhibitory immunoglobulins (TBII) were estimated before and after 6 weeks of
      treatment. Duplex Doppler ultrasonographic examination of the thyroid, inferior
      thyroid artery (ITA), and common carotid artery (CCA) was performed before and
      after 2, 4, and 6 weeks of therapy. RESULTS: Serum FT(4) and TBII decreased after
      treatment in both groups, whereas serum TSH increased in group I only. The volume
      of the thyroid gland and parenchymal blood velocity were increased in these
      patients and diminished only with addition of propranolol to carbimazole. A
      diffuse hypoechogenic pattern in the thyroid gland and increased ITA blood flow
      and peak velocity were observed in all patients and persisted throughout
      treatment. The mean CCA peak blood velocity was accelerated in Graves' disease
      and diminished after 6 weeks of therapy in both groups, whereas increased CCA
      blood flow diminished only in group I. CONCLUSION: A 6-week period of therapy
      with carbimazole and propranolol has no effect on the diffuse low echogenic
      pattern in the thyroid gland and the accelerated ITA blood flow in Graves'
      disease. The addition of propranolol is associated with early decrements in
      thyroid volume, parenchymal vascularity, and CCA blood flow as well as early
      recovery of TSH suppression, but it has no additional effect on thyroid hormone
      secretion or TBII levels.

PMID- 15251796
TI  - Some characteristics of primary hyperparathyroidism in Vietnamese immigrants
      living in Southern California.
AB  - OBJECTIVE: To characterize primary hyperparathyroidism (PHP) in Vietnamese
      immigrants living in southern California and to summarize the results of
      treatment. METHODS: We describe 11 patients (8 women and 3 men) with a mean age
      of 57.91 years who underwent follow-up from 1991 to 1995 after PHP was diagnosed.
      The patients had no specific complaints. Four patients had a history of kidney
      stones, and five had chronic hypertension. Only five patients had high levels of
      total serum calcium; the other six patients had normal or fluctuating levels of
      total serum calcium. All patients, however, had high levels of intact parathyroid
      hormone (PTH) and ionized calcium. Preoperatively, parathyroid imaging with
      technetium-99m sestamibi demonstrated persistently increased parathyroid gland
      uptake. RESULTS: In all nine patients who underwent surgical treatment, an
      adenoma was found in the parathyroid glands; two patients refused operative
      intervention. The mean serum phosphate was in the low-normal range and increased
      postoperatively (2.70 versus 3.52 mg/dL; P<0.001). The mean serum chloride level
      also decreased postoperatively (104.62 versus 100.78 mEq/L; P<0.001). The ratio
      of chloride/phosphate decreased significantly after adenoma removal (39.44 versus
      29.21; P<0.001). Six patients received calcium gluconate either alone or in
      combination with vitamin D supplements for hypocalcemia postoperatively. The
      other three patients, however--who did not receive calcium supplements
      postoperatively--had persistently high levels of intact PTH but normal serum Ca++
      levels and subsequently were treated effectively with calcium gluconate and
      vitamin D. CONCLUSION: The presence of hypercalcemia, especially Ca++, and an
      increased level of intact PTH establishes the diagnosis of PHP. After
      parathyroidectomy, the persistence of high levels of intact PTH in association
      with normal serum Ca++ suggested the presence of secondary hyperparathyroidism,
      which was treated effectively with calcium gluconate and vitamin D. These
      patients had the same clinical picture as other ethnic groups with PHP, but they
      needed either calcium alone or calcium and vitamin D supplements after
      parathyroidectomy because of their bone loss from prolonged PHP.

PMID- 15251797
TI  - Malignant nonfunctioning pheochromocytoma occurring in a mixed multiple endocrine
      neoplasia syndrome.
AB  - OBJECTIVE: To present the first documented case of malignant nonfunctioning
      pheochromocytoma occurring in a mixed multiple endocrine neoplasia (MEN)
      syndrome. METHODS: We describe the personal and family history of a 34-year-old
      man with headaches, increased serum prolactin levels, and hyperparathyroidism and
      review the details of his clinical course and treatment. RESULTS: After diagnosis
      of a prolactinoma, bromocriptine therapy was implemented but eventually
      discontinued by the patient when severe headaches recurred. A transsphenoidal
      resection of a prolactinoma was performed; the patient continued to have
      abnormally high serum prolactin levels. Subsequent left lower flank pain prompted
      an exploratory laparotomy, and a left nephroad-renalectomy was performed.
      Pathologic examination disclosed a 1-cm tumor, consistent with malignant
      pheochromocytoma. Electron microscopy demonstrated neurosecretory granules. A
      hypercoagulable state complicated the course postoperatively. Despite
      chemotherapy, extensive metastatic disease ensued, and the patient died.
      CONCLUSION: Although pheochromocytomas are usually associated with MEN type IIA
      and type IIB, this patient had a malignant pheochromocytoma, without the usual
      clinical and biochemical manifestations, in the setting of MEN type I.

PMID- 15251798
TI  - Recombinant human granulocyte colony-stimulating factor in treatment of
      methimazole-induced agranulocytosis.
AB  - OBJECTIVE: To describe a patient with methimazole-induced agranulocytosis who was
      treated with recombinant human granulocyte colony-stimulating factor (G-CSF).
      METHODS: A case report is presented, in which the clinical and laboratory
      findings are detailed and the response to treatment is discussed. Pertinent
      reports from the literature are reviewed. RESULTS: In a 24-year-old woman with
      Graves' disease who was treated with methimazole, a fever and sore throat
      developed; bone marrow examination revealed absence of granulocytes. After
      discontinuation of methimazole therapy, treatment with G-CSF was implemented in
      an attempt to hasten the reappearance of the granulocytes. The patient's
      granulocyte count reached 0.5 10(9)/L on the 9th hospital day and was more than
      1.5 10(9)/L on the 10th day. Because the recovery time for thionamide-induced
      agranulocytosis typically ranges from 1 to 2 weeks and sometimes is even longer,
      G-CSF may have been beneficial in accelerating the return of the granulocytes.
      CONCLUSION: Only a small number of patients with thionamide-induced
      agranulocytosis have had G-CSF treatment, and most outcomes have generally
      supported a beneficial effect. More experience is needed with the use of G-CSF in
      such circumstances. Nevertheless, its use seems to be a reasonable therapeutic
      option for consideration in patients with thionamide-induced agranulocytosis.

PMID- 15251799
TI  - Dyslipidemia as a risk factor for coronary disease in patients with diabetes.
AB  - OBJECTIVE: To highlight the frequency of lipid abnormalities in patients with
      diabetes and the need for appropriate treatment strategies for coronary disease.
      METHODS: The epidemiologic features of coronary artery disease in the diabetic
      population are reviewed, and the pathogenesis of atherosclerotic disease is
      discussed. Various risk factors for predicting coronary artery disease and
      guidelines for therapeutic intervention are presented. RESULTS: The American
      Diabetes Association has estimated that 60% of all adults will die of coronary
      artery disease and that 80% of patients with diabetes will ultimately have
      atherosclerosis. The accelerated rate of atherosclerosis in patients with
      diabetes may be attributable to several factors, including hyperglycemia and
      insulin resistance. Abnormalities in lipid metabolism have a major role in the
      development of coronary disease. Because the National Cholesterol Education
      Program guidelines for treatment were established for less complicated
      hyperlipidemias, The American Diabetes Association recommends more aggressive
      lipid-lowering therapy at a lower level of low-density lipoproteins (130 mg/dL or
      3.36 mmol/L) to produce an equivalent reduction in risk of coronary disease in
      patients with diabetes. CONCLUSION: In patients with diabetes, lipid levels
      should be aggressively reduced to decrease the possibility of coronary artery
      disease.

PMID- 15251800
TI  - Management of hyperlipidemia in women with diabetes.
AB  - OBJECTIVE: To review gender-related factors in coronary artery disease, possible
      mechanisms for increased atherogenesis in women with diabetes, and potential
      therapeutic strategies for hyperlipidemia. METHODS: Pertinent published studies
      and personal experiences are discussed, and lipoprotein profiles are outlined.
      RESULTS: In the normal population, the increase in atherosclerotic vascular
      disease with aging in women lags behind that in men by 10 to 15 years. With the
      presence of diabetes, however, the atherosclerotic changes are similar in men and
      women. Several studies have substantiated that triglyceride levels are a stronger
      risk factor than cholesterol in men and women with diabetes who have coronary
      artery disease. In general, hypertriglyceridemia is a stronger risk factor for
      cardiovascular disease in women than in men. Gender differences in lipid levels
      can be explained physiologically by the presence of estrogen in female patients,
      which accelerates the rate of metabolism of lipoproteins and, in a setting of
      insulin deficiency, induces hypertriglyceridemia. Dietary measures and various
      classes of drugs, including reductase inhibitors, are used alone or in
      combination for management of the combined hyperlipidemia typically found in
      subjects with insulin resistance, diabetes, or both. CONCLUSION: Gender-related
      differences in lipoprotein-associated cardiovascular risk should be considered in
      choosing treatment options for patients with diabetes and hyperlipidemia.

PMID- 15251801
TI  - Current and future trends in therapy for dyslipidemias.
AB  - OBJECTIVE: To characterize the atherogenic lipoprotein profile and discuss its
      implications in terms of treatment. METHODS: Findings from large clinical trials
      and personal series of patients are reviewed, and the effectiveness of various
      interventions is assessed. A cost analysis of management of patients with
      dyslipidemias is offered. RESULTS: The dyslipidemia associated with non-insulin
      dependent diabetes mellitus (NIDDM) is similar to low-density lipoprotein (LDL)
      pattern B. This atherosclerosis susceptibility trait--which typically consists of
      a preponderance of small dense LDL particles, intermediate-density lipoprotein,
      slightly increased triglycerides, and inappropriately low high-density
      lipoprotein type 2-- tends to precede the actual diagnosis of NIDDM and to
      identify a group with increased risk for cardiovascular events. It also usually
      signifies a group with good responses to treatment, including arteriographic
      evidence of regression of coronary artery disease. In general, niacin and
      fibrates are superior to statins for treatment of patients with LDL pattern B.
      Lipid management has been proved to be a cost-effective treatment strategy.
      CONCLUSION: Therapeutic options that lower triglyceride-rich lipoproteins and
      small dense LDL should be recommended in patients with NIDDM.

PMID- 15251802
TI  - Expanding the list of etiologic factors for osteoporosis in men.

PMID- 15251803
TI  - Management of Paget's disease of bone in the era of new and more potent
      bisphosphonates.

PMID- 15251828
TI  - Assessment of therapy with continuous subcutaneous insulin infusion in an
      academic diabetes clinic.
AB  - OBJECTIVE: To assess the results of continuous subcutaneous insulin infusion
      (CSII) therapy in patients with type 1 diabetes mellitus, especially relative to
      glycemic control and rate of discontinuation of insulin pump therapy. METHODS: A
      retrospective review of the medical records of 107 patients with type 1 diabetes
      who were receiving CSII at the Diabetes Care Center at the University of
      Washington Medical Center was performed to evaluate clinical outcomes. All
      patients considering CSII therapy participated in a class to learn the details of
      insulin pump treatment. RESULTS: The mean age of our patient population was 36.0
      +/- 10.4 years (mean value +/- standard deviation). The mean duration of diabetes
      at the initiation of insulin pump therapy was 17.0 +/- 9.1 years. The mean
      duration of CSII use was 36.1 +/- 25.5 months (median, 26.2 months). Insulin
      lispro was used by 89.7% of the patients. Six patients (5.6%) discontinued CSII
      therapy after a mean of 19.1 +/- 14.7 months for a variety of reasons. Despite no
      significant difference in home blood glucose monitoring (number of tests per day)
      before initiation of CSII, mean hemoglobin A1c levels decreased from 7.6% to 7.1%
      (P<0.0001), and the occurrence of severe hypoglycemic episodes decreased 73.8% (P
      = 0.0003). CONCLUSION: In our academic diabetes clinic with a formal insulin pump
      program, we noted a significant improvement in hemoglobin A1c values, a
      significant reduction in the frequency of severe hypoglycemic episodes, and a low
      rate of discontinuation of CSII. CSII therapy, when provided in conjunction with
      a standard educational program, should continue to be an important treatment
      option in appropriately selected patients with type 1 diabetes.

PMID- 15251829
TI  - Lipoprotein effects of different thiazolidinediones in clinical practice.
AB  - OBJECTIVE: To investigate and compare the effects of troglitazone and
      rosiglitazone on plasma lipoproteins in patients with type 2 diabetes mellitus
      and dyslipidemia. METHODS: This cohort study was conducted in the Diabetes Clinic
      of the University of Alabama. We identified and studied 18 patients with type 2
      diabetes and dyslipidemia first treated with troglitazone (600 mg/day) and then
      transferred to rosiglitazone therapy (8 mg/day). RESULTS: By lowering insulin
      resistance, thiazolidinediones have common effects on lipoproteins; however,
      these drugs may have important differences in their effects on individual lipid
      particles. In our patients, both troglitazone and rosiglitazone increased low
      density lipoprotein (LDL) levels; however, only rosiglitazone significantly
      changed the LDL particle size to the larger, less atherogenic LDL particle.
      Similarly, both troglitazone and rosiglitazone increased high-density lipoprotein
      (HDL) concentrations; however, although troglitazone increased only HDL(3),
      rosiglitazone also significantly increased the larger, more cardioprotective
      HDL(2) particle. Furthermore, only troglitazone increased Lp(a) significantly. In
      contrast, rosiglitazone and not troglitazone significantly increased
      triglycerides. CONCLUSION: Small but significant differences exist in the effects
      of different thiazolidinediones on lipoproteins in patients with type 2 diabetes.
      Overall, the changes in lipoprotein profile induced by rosiglitazone therapy seem
      to have less atherogenic potential than those resulting from the use of
      troglitazone.

PMID- 15251830
TI  - Comparison between continuous subcutaneous insulin infusion and multiple insulin
      injection therapy in type 1 diabetes mellitus: 18-month follow-up.
AB  - OBJECTIVE: To compare the results with continuous subcutaneous insulin infusion
      (CSII) versus multiple daily injections (MDI) of insulin in the treatment of type
      1 diabetes during 18 months of follow-up. METHODS: We prospectively studied 29
      patients with type 1 diabetes in Brazil; 17 patients elected to change from
      conventional insulin therapy (2 injections daily) (N = 3) or MDI (N = 14) to CSII
      therapy, and the other 12 continued to receive MDI therapy. All patients were
      treated with insulin lispro; patients in the MDI treatment group also received
      NPH insulin. We compared hemoglobin A1c (HbA1c) values, determined at baseline
      and every 3 months, between the two treatment groups. Other variables analyzed
      included weight, body mass index, total daily dose of insulin, and incidence of
      severe hypoglycemia. RESULTS: Patients in the CSII group had a significant
      decrease (P<0.001) in mean HbA1c at 18 months in comparison with baseline (8.3%
      versus 6.5%). In the MDI group, no significant changes were found in mean HbA1c.
      After 3 months of treatment, patients in the CSII group had a significantly lower
      mean HbA1c level than did patients receiving MDI (P<0.05). Of the 17 patients
      treated with CSII, all had HbA1c values less than 7.5% at 18 months, and 13 (76%)
      had HbA1c levels less than 7%. Although no significant variations in weight were
      observed in either group, the insulin/weight ratio decreased in the CSII group
      from baseline to 18 months (0.8 U/kg to 0.6 U/kg; P = 0.02). No episodes of
      severe hypoglycemia were noted in either group. CONCLUSION: Patients with
      diabetes treated with insulin lispro have better glycemic control with CSII than
      with MDI. Most of our patients in the CSII group were able to achieve target
      HbA1c levels less than 7% at 18 months without an increase in hypoglycemic
      episodes.

PMID- 15251831
TI  - Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether the administration of D-chiro-inositol, a
      putative insulin-sensitizing drug, would affect the concentration of circulating
      insulin, the levels of serum androgens, and the frequency of ovulation in lean
      women with the polycystic ovary syndrome. METHODS: In 20 lean women (body mass
      index, 20.0 to 24.4 kg/m 2) who had the polycystic ovary syndrome, treatment was
      initiated with either 600 mg of D-chiro-inositol or placebo orally once daily for
      6 to 8 weeks. We performed oral glucose tolerance tests and measured serum sex
      steroids before and after therapy. To monitor for ovulation, we determined serum
      progesterone concentrations weekly. RESULTS: In the 10 women given D-chiro
      inositol, the mean (+/- standard error) area under the plasma insulin curve after
      oral administration of glucose decreased significantly from 8,343 +/- 1,149 mU/mL
      per min to 5,335 +/- 1,792 mU/mL per min in comparison with no significant change
      in the placebo group (P = 0.03 for difference between groups). Concomitantly, the
      serum free testosterone concentration decreased by 73% from 0.83 +/- 0.11 ng/dL
      to 0.22 +/- 0.03 ng/dL, a significant change in comparison with essentially no
      change in the placebo group (P = 0.01). Six of the 10 women (60%) in the D-chiro
      inositol group ovulated in comparison with 2 of the 10 women (20%) in the placebo
      group (P = 0.17). Systolic (P = 0.002) and diastolic (P = 0.001) blood pressures,
      as well as plasma triglyceride concentrations (P = 0.001), decreased
      significantly in the D-chiro-inositol group in comparison with the placebo group,
      in which these variables either increased (blood pressure) or decreased minimally
      (triglycerides). CONCLUSION: We conclude that, in lean women with the polycystic
      ovary syndrome, D-chiro-inositol reduces circulating insulin, decreases serum
      androgens, and ameliorates some of the metabolic abnormalities (increased blood
      pressure and hypertriglyceridemia) of syndrome X.

PMID- 15251832
TI  - Bacterial pituitary abscess: an unusual cause of panhypopituitarism.
AB  - OBJECTIVE: To describe a case of primary bacterial pituitary abscess manifesting
      as hypopituitarism. METHODS: We present the case history, hormonal and
      bacteriologic data, and findings on imaging studies in a 34-year-old man.
      RESULTS: The patient had an 8-month history of intermittent fever, headache,
      nausea, vomiting, and weight loss. Because a computed tomographic scan of the
      head showed a cystic sellar mass with ring enhancement, he was referred to our
      medical center. On physical examination, he showed signs of meningeal irritation
      and had mild hypotension. Hormonal evaluation revealed evidence of
      hypocortisolism, hypothyroidism, and hypogonadism. Three weeks after treatment
      with antibiotics and hormonal replacement, he underwent transsphenoidal surgical
      exploration and evacuation of purulent material from the sella. On culture, this
      specimen grew coagulase-negative staphylococci and Propionibacterium granulosum.
      Nine months later, dynamic testing showed persistent central hypocortisolism,
      hypothyroidism, and hypogonadism. CONCLUSION: Bacterial pituitary abscess is rare
      but manifests similar to other pituitary masses with headaches, visual field
      defects, and hormonal disturbances. For the correct preoperative diagnosis of
      this condition, the physician must have a high index of suspicion, and the
      characteristic ring enhancement must be present on imaging studies.

PMID- 15251833
TI  - Multiple tumors associated with late-onset congenital adrenal hyperplasia due to
      aberrant splicing of adrenal 21-hydroxylase gene.

PMID- 15251834
TI  - Combined use of calcium infusion localization and a minimally invasive surgical
      procedure in the management of insulinoma.
AB  - OBJECTIVE: To review our experience with current diagnostic localization
      techniques and a minimally invasive laparoscopic surgical procedure in the
      management of insulinoma. METHODS: We describe five patients with insulinoma, the
      results of diagnostic studies, and a proposed algorithm for management of this
      rare tumor. RESULTS: Four female patients and one male patient (age range, 34 to
      72 years) underwent supervised fasting (mean duration, 12 hours; range, 3 to 28
      hours) to establish the diagnosis of insulinoma. These patients had glucose
      values that ranged from 38 to 41 mg/dL and associated serum insulin levels of
      11.3 to 61 microU/mL. C-peptide values ranged from 3.4 to 11.5 ng/mL, and
      proinsulin levels (measured in four patients) were 32.9 to 82 pmol/L. These
      biochemical findings were diagnostic for insulin-mediated hypoglycemia, and the
      high proinsulin and C-peptide levels, in conjunction with negative results of
      serum measurements for sulfonylureas, excluded an exogenous source of insulin as
      the cause of hypoglycemia. Four of the five study patients had nondiagnostic
      results of noninvasive localization studies and underwent selective arterial
      injection of calcium with hepatic venous sampling to help localize the
      insulinomas within the pancreas. This procedure correctly localized the lesion in
      three patients and was associated with no complications. In all five patients,
      surgical resection of a solitary insulinoma (with use of laparoscopic procedures
      in four, one of which was converted to an open procedure) yielded resolution of
      the hypoglycemia. CONCLUSION: The combination of calcium infusion localization
      and a minimally invasive surgical procedure is an efficient management approach
      in the diagnosis and treatment of insulinoma.

PMID- 15251835
TI  - Diabetic myonecrosis in a previously healthy woman and review of a 25-year Mayo
      Clinic experience.
AB  - OBJECTIVE: To describe a case of diabetic myonecrosis, an unusual complication of
      diabetes mellitus, and to provide an overview of an institutional experience with
      this condition. METHODS: We report the clinical, laboratory, and imaging findings
      in a 50-year-old woman with no history of diabetes, who was hospitalized because
      of weakness in her left lower extremity and an infection in her right hand.
      RESULTS: A morbidly obese woman had sustained several falls attributable to left
      leg weakness, which had resulted in repetitive trauma to, and subsequent
      infection of, her right hand. Laboratory studies showed a fasting blood glucose
      level of 204 mg/dL, a glycated hemoglobin of 12.8%, and a calculated hemoglobin
      Alc of 10.6%. Results of evaluations for retinopathy and nephropathy were
      negative. Electromyography of the left leg suggested the presence of a diabetic
      plexopathy. Two weeks after admission of the patient, severe left lower extremity
      pain and swelling developed abruptly. Ultrasound evaluation of the leg was
      negative for deep venous thrombosis. Laboratory data revealed a leukocyte count
      of 7.1 x 10(3)/mL and a creatine kinase level of 26 U/L. Magnetic resonance
      imaging of the left leg demonstrated extensive muscle edema and collections of
      fluid surrounding the femur and posterior compartment of the thigh and extending
      into the left calf. Gram stain and cultures of aspirated fluid were negative. The
      patient was managed with supportive care, including strict glycemic control,
      periodic analgesia, and physical therapy. A review of medical records for a 25
      year period at the Mayo Clinic disclosed only five patients with the diagnosis of
      diabetic myonecrosis. All five patients had insulin-treated diabetes and severe
      end-organ disease. CONCLUSION: The current case is the first report of
      myonecrosis as the initial manifestation of diabetes. This case also demonstrates
      that myonecrosis, although typically involving the thigh, can extend abruptly to
      the calf. Diabetic myonecrosis should be included in the differential diagnosis
      of an acutely painful lower extremity mass in patients with diabetes.

PMID- 15251836
TI  - Comparison of urinary iodine excretion in neonates and their mothers in Isfahan,
      Iran.
AB  - OBJECTIVE: To determine the urinary iodine excretion of neonates (28 days of age
      or younger) and their mothers in Isfahan, a centrally located city in Iran, in
      1997 after 8 years of iodized salt distribution in an effort to ameliorate iodine
      deficiency. METHODS: Through a cross-sectional study and by means of convenient
      sampling, 146 mother-neonate pairs were selected among neonates born in Shahid
      Sadoughi Hospital in Isfahan. In order to eliminate the effect of povidone-iodine
      on breast milk and urinary iodine, Savlon antiseptic solution was used in normal
      vaginal delivery and on the umbilical cord. Normal values of urinary iodine
      concentration for the mothers and their neonates were > or = 10.0 microg/dL and
      >5.0 microg/dL, respectively. The data were analyzed and compared by the Student
      t test and Pearson correlation coefficient in SPSS software. P values <0.05 were
      considered statistically significant. RESULTS: In only 3% of the neonates and 14%
      of the mothers, urinary iodine excretion was below the normal range. No mother or
      neonate had severe iodine deficiency. In 2% of the mothers and 2% of the
      neonates, mild iodine deficiency was found. The mean urinary iodine concentration
      of neonates whose mothers were iodine deficient was significantly lower than that
      of neonates whose mothers were iodine sufficient (17.34 +/- 7.83 microg/dL versus
      22.21 +/- 7.57 microg/dL; P<0.01). A direct significant correlation was noted
      between the urinary iodine excretion of neonates and that of their mothers (r =
      0.37; P<0.01). CONCLUSION: The urinary iodine excretion in mothers paralleled the
      urinary iodine concentration of their neonates. If urinary iodine concentration
      is considered an index of total body iodine content, this study demonstrated that
      prolonged iodized salt intake has minimized the occurrence of iodine deficiency
      in Isfahan.

PMID- 15251837
TI  - Accuracy and precision of the NovoPen 3 insulin delivery device after mechanical
      and temperature stresses.
AB  - OBJECTIVE: To evaluate the precision, accuracy, and durability of an insulin pen
      injection device (NovoPen 3) at three preset doses (2 IU, 35 IU, and 70 IU) after
      exposure to various stress and durability tests that were intended to simulate
      daily use by patients. METHODS: Twenty-nine reusable NovoPen 3 insulin delivery
      devices were tested. The precision and accuracy of 10 insulin pen devices were
      evaluated after they were subjected to multiple thermal and vibration stress
      tests. Another 10 pen devices were subjected to a free-fall test. Nine other
      insulin pens were subjected to endurance testing that simulated 5 years of
      injections. RESULTS: The accuracy (as measured by the relative error of the
      delivered dose of insulin) of the insulin pen injection devices was within 1% of
      the preset dose after all stress or endurance tests. A free-fall test produced no
      indication of damage except for broken clips and snap catches on the caps, which
      did not affect the integrity or performance of the insulin pens. The precision of
      the pen devices (as measured by relative standard deviations of delivered volumes
      of insulin) was likewise high after thermal stress, vibration stress, free-fall
      testing, or 5-year endurance testing. CONCLUSION: Overall, this study showed that
      the insulin pen injection devices tested were durable under conditions of stress
      likely to be encountered in daily patient use. Neither a wide variety of
      repetitive stresses nor insulin injection cycles corresponding to 5 years of use
      affected the accuracy or precision enough to have clinical significance for
      reliable insulin delivery.

PMID- 15251838
TI  - Pituitary neurologic surgery: a unique subspecialty in evolution.
AB  - OBJECTIVE: To review the evolving approaches to surgical management of pituitary
      tumors during the past century, which may predict future directions. METHODS: We
      undertook a retrospective review of selected literature published during the past
      century and report the trends in the treatment of pituitary tumors. RESULTS:
      Harvey Cushing's extraordinary influence on American neurosurgery and remarkably
      successful pituitary surgical series were the foundation for the development of a
      highly subspecialized neurosurgical operative field. Continued evolution in the
      treatment of pituitary tumors has been historically based on the following: (1)
      the development of exogenous cortisone and vasopressin; (2) the development of
      high-voltage and nuclear radiation therapy; (3) the experience gained from total
      hypophysectomy for "endocrine" driven malignant lesions and diabetic retinopathy;
      (4) the development of the image intensifier and television intraoperative
      fluoroscopic control; (5) the use of endoscopes in pituitary surgical procedures;
      (6) the application of the operating microscope to transsphenoidal approaches;
      (7) the development of the imaging modalities of computed tomographic scanning
      and subsequent magnetic resonance imaging; and (8) the concepts surrounding
      "minimally invasive" surgical techniques. CONCLUSION: The pituitary surgical
      techniques of today have evolved primarily because of extraordinary past
      accomplishments. The approaches used continue to maximize tumor resection and
      preserve functioning pituitary tissue. New intraoperative imaging techniques will
      forge the future of the field of pituitary neurosurgery, and the expected
      outcomes will be improved surgical success and lower perioperative morbidity.)

PMID- 15251839
TI  - Addisonian crisis and tuberculous epididymo-orchitis.
AB  - OBJECTIVE: To describe a case of acute primary adrenal insufficiency in which
      tuberculosis was subsequently detected as the etiologic factor when the patient
      presented with tuberculous epididymo-orchitis. METHODS: A case of acute primary
      adrenal insufficiency associated with bilaterally enlarged adrenal glands is
      reported, along with the subsequent finding of a scrotal mass diagnosed as
      tuberculous epididymo-orchitis. Diagnosis, adrenal function, and results of
      imaging studies after institution of antituberculous treatment are discussed.
      RESULTS: A 41-year-old Egyptian man, who had immigrated to the United States 5
      years previously, had acute psychosis and addisonian crisis. A substantially
      increased early morning level of plasma adrenocorticotropic hormone and a low
      level of serum cortisol confirmed the diagnosis of primary adrenal insufficiency.
      Both adrenal glands were enlarged but without calcification on computed
      tomography. A previous bacille Calmette-Guerin vaccination complicated the
      interpretation of a positive tuberculin skin test result. Both lungs were clear
      on chest radiography and computed tomography. Seven months later, the patient had
      a left scrotal mass and underwent radical orchiectomy. Examination of the
      pathology specimen showed caseous granulomatous inflammation and necrosis, and
      acid-fast bacilli were identified. Culture was positive for Mycobacterium
      tuberculosis. CONCLUSION: In a patient from a country where tuberculosis is
      endemic, tuberculosis should be considered in the differential diagnosis when
      primary adrenal insufficiency is detected, especially in association with
      enlarged or calcified adrenal glands. Extra-adrenal tuberculous involvement
      should be actively sought because it may provide indirect microbiologic or
      histologic clues. Other than the lungs, special attention should be paid to the
      genitourinary system.

PMID- 15251840
TI  - A malignant aldosteronoma.
AB  - OBJECTIVE: To describe a case of primary aldosteronism due to an adrenocortical
      carcinoma (ACC) and highlight the need for thorough long-term follow-up. METHODS:
      We present the clinical, laboratory, radiologic, and pathologic findings in a
      patient with ACC and review the related literature. RESULTS: A 52-year-old woman
      with a history of hypertension and hypokalemia was referred for evaluation of a 6
      cm adrenal mass. Her biochemical studies revealed a serum aldosterone-to-renin
      ratio of 52 without evidence of cortisol, catecholamine, or androgen excess. She
      underwent surgical resection of this mass, and histologic analysis showed a
      focally brisk mitotic rate but no evidence of capsular or vascular invasion. In
      light of these findings, the biologic nature of the tumor was difficult to
      predict. Thus, it was thought to be an adrenocortical neoplasm. The patient
      underwent follow-up clinically, biochemically, and with interval computed
      tomography. Nine years later, hypertension and hypokalemia redeveloped, and she
      was found to have metastatic ACC. CONCLUSION: ACC can generally be reliably
      diagnosed; however, in some cases, the true biologic behavior is difficult to
      predict. We emphasize the importance of careful clinical, biochemical, and
      radiologic surveillance in these difficult cases because surgical resection
      provides the best opportunity for cure in patients with adrenal cancer.

PMID- 15251841
TI  - Coexistence of malignant struma ovarii and Graves' disease.
AB  - OBJECTIVE: To report an unusual case of hyperthyroidism from Graves' disease that
      was coexistent with malignant struma ovarii. METHODS: We summarize the clinical
      history, physical findings, laboratory data, imaging studies, pathologic
      features, and treatment in a patient with recurrent hyperthyroidism and discuss
      the incidence of ovarian tumors of various histologic origins, including thyroid
      tissue (that is, struma ovarii). RESULTS: Five years after diagnosis of Graves'
      disease and resolution of symptoms with 1 year of antithyroid drug therapy, a 53
      year-old woman had recurrence of palpitations, tremors, and weight loss. Results
      of thyroid function tests showed high total and free thyroxine levels and a low
      thyrotropin level. Thyroid radioiodine uptake was high (69% at 24 hours).
      Abdominal ultrasound studies disclosed a cystic mass in the right adnexal area.
      Total abdominal hysterectomy and bilateral oophorectomy revealed a 7.5-cm cystic
      right ovary that contained a 1.0-cm struma ovarii with a 0.4-cm nodule of
      follicular variant papillary thyroid carcinoma within it. The patient was treated
      with methimazole and radioiodine ablation of the thyroid. Three months later, a
      massive myocardial infarction resulted in her death. CONCLUSION: The concomitant
      presence of Graves' disease complicates the management of struma ovarii and
      raises interesting questions about treatment and prognosis.

PMID- 15251842
TI  - Ectopic adrenocorticotropic hormone syndrome caused by metastatic carcinoma of
      the prostate: therapeutic response to ketoconazole.

PMID- 15251843
TI  - Ask your doctor.

PMID- 15251846
TI  - Legislative perspectives on diabetes in America.
AB  - PURPOSE: To highlight the ongoing legislative activity in support of diabetes
      management. FINDINGS: Efforts of the Senate Diabetes Caucus have been
      instrumental in increasing the budget of the National Institutes of Health from
      $13.6 billion to $20.4 billion during the past 3 years, including more than
      doubling of the funding for diabetes research (from $319 million to $690
      million). The demonstrated effectiveness of the Diabetes Prevention Program in
      delaying or preventing the development of type 2 diabetes by use of diet and
      exercise or metformin emphasizes the importance of diabetes educational programs
      for high-risk persons. CONCLUSION: Government funding of diabetes educational and
      research programs improves the quality of life for patients with diabetes and
      ultimately saves money.

PMID- 15251847
TI  - Hemoglobin A1c: need to standardize the term.
AB  - PURPOSE: To discuss studies that investigate the understanding of patients with
      diabetes and the information provided by physicians regarding the terminology and
      meaning of tests for glycated hemoglobin. FINDINGS: Patients with diabetes seldom
      know or remember the terminology for glycated hemoglobin assay techniques, even
      when they are participating in self-monitoring of blood glucose. Physicians use a
      variety of terms for the glycated hemoglobin test and are not consistent in their
      terminology. CONCLUSION: One term for glycated hemoglobin assay should be used
      and promoted by all health-care professionals and patients. Because it is most
      readily remembered, "A1C" is the preferred lay term.

PMID- 15251862
TI  - Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from
      normal cats and cats with interstitial cystitis.
AB  - Purinergic mechanisms appear to be involved in motor as well as sensory functions
      in the urinary bladder. ATP released from efferent nerves excites bladder smooth
      muscle, whereas ATP released from urothelial cells can activate afferent nerves
      and urothelial cells. In the present study, we used immunohistochemical
      techniques to examine the distribution of purinoceptors in the urothelium, smooth
      muscle, and nerves of the normal cat urinary bladder as well as possible changes
      in the expression of these receptors in cats with a chronic painful bladder
      condition termed feline interstitial cystitis (FIC) in which ATP release from the
      urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3),
      P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor
      subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a
      marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and
      P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in
      staining were detected in FIC. Smooth muscle in the normal bladder did not
      exhibit P2Y receptor staining but did exhibit P2X (P2X(2), P2X(1)) staining. In
      the FIC bladder smooth muscle, there was a significant reduction in P2X(1)
      expression. These findings raise the possibility that purinergic mechanisms in
      the urothelium and bladder smooth muscle are altered in FIC cats. Because the
      urothelial cells appear to have a sensory function in the bladder, it is possible
      that the plasticity in urothelial purinergic receptors is linked with the painful
      bladder symptoms in IC.

PMID- 15251861
TI  - Angiotensin II induces carbon monoxide production in the perfused kidney:
      relationship to protein kinase C activation.
AB  - Heme oxygenase (HO)-derived carbon monoxide (CO) attenuates vascular reactivity
      to constrictor stimuli. ANG II produces vasoconstriction and induces HO-1 isoform
      expression. However, direct evidence that ANG II promotes HO product generation
      is lacking. Therefore, we examined the effects of ANG II on CO release and HO
      isoform expression in isolated rat kidneys. Kidneys were perfused with oxygenated
      Krebs buffer. ANG II (1 micromol/l) increased (P < 0.05) perfusion pressure from
      97 +/- 9 to 150 +/- 14 mmHg; it also increased (P < 0.05) the concentration of CO
      in the venous effluent (from 27.1 +/- 11.9 to 45.6 +/- 11.7, 62.5 +/- 16.7, 94.8
      +/- 20.7, and 101.9 +/- 13.1 nmol/l after 30, 60, 90, and 120 min, respectively).
      The pressor effect of ANG II was blunted (P < 0.05) in kidneys perfused with
      buffer containing losartan (10 micromol/l) or PKC inhibitors staurosporine (0.1
      micromol/l) or calphostin C (1 micromol/l). Kidneys perfused with buffer
      containing ANG II for 120 min also displayed increased (P < 0.05) HO-1
      expression. Stannous mesoporphyrin (30 micromol/l) decreased CO release (P <
      0.05) in preparations perfused with and without ANG II; the HO inhibitor also
      increased (P < 0.05) perfusion pressure, more so in kidneys perfused with that
      without ANG II. We conclude that ANG II stimulates CO production and release in
      isolated, perfused rat kidneys. This action of ANG II is linked to the activation
      of AT(1) receptors and involves PKC activation and upregulation of renal HO-1 but
      not of HO-2 protein expression. The study suggests upregulation of renal HO-1 and
      CO release are protagonic events in a counterregulatory mechanism that attenuates
      ANG II-induced renal vasoconstriction.

PMID- 15251863
TI  - Relative contribution of OAT and OCT transporters to organic electrolyte
      transport in rabbit proximal tubule.
AB  - We compared the characteristics of several cloned rabbit organic electrolyte (OE)
      transporters expressed in cultured cells with their behavior in intact rabbit
      renal proximal tubules (RPT) to determine the contribution of each to basolateral
      uptake of the weak acid ochratoxin A (OTA) and the weak base cimetidine (CIM).
      The activity of organic anion transporters OAT1 and OAT3 proved to be
      distinguishable because OAT1 had a high affinity for PAH (K(t) of 20 microM) and
      did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity
      for ES (K(t) of 4.5 microM) and a weak interaction with PAH (IC(50) > 1 mM). In
      contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated
      OTA, with OAT1 and OAT3 each responsible for approximately 50%: ES and PAH each
      reduced uptake by approximately 50%, and the combination of the two eliminated
      mediated OTA uptake. The weak base CIM was transported by OAT3 (K(t) of 80
      microM) and OCT2 (K(t) of 2 microM); OCT1 had a comparatively low affinity for
      CIM, and CIM uptake by OAT1 was equivocal. Intact RPT accumulated CIM, with TEA
      and ES reducing CIM uptake by 20 and 75%, respectively, suggesting that OAT3
      plays a quantitatively more significant role in CIM uptake in the early proximal
      tubule than OCT1/2. In single S2 segments of RPT, ES and TEA each blocked
      approximately 50% of CIM uptake. Thus the fractional contribution of different OE
      transporters to renal secretion is influenced by their affinity for substrate and
      relative expression level in RPT.

PMID- 15251864
TI  - Urea may regulate urea transporter protein abundance during osmotic diuresis.
AB  - Rats with diabetes mellitus have an increase in UT-A1 urea transporter protein
      abundance and absolute urea excretion, but the relative amount (percentage) of
      urea in total urinary solute is actually decreased due to the marked glucosuria.
      Urea-specific signaling pathways have been identified in mIMCD3 cells and renal
      medulla, suggesting the possibility that changes in the percentage or
      concentration of urea could be a factor that regulates UT-A1 abundance. In this
      study, we tested the hypothesis that an increase in a urinary solute other than
      urea would increase UT-A1 abundance, similar to diabetes mellitus, whereas an
      increase in urine urea would not. In both inner medullary base and tip, UT-A1
      protein abundance increased during NaCl- or glucose-induced osmotic diuresis but
      not during urea-induced osmotic diuresis. Next, rats undergoing NaCl or glucose
      diuresis were given supplemental urea to increase the percentage of urine urea to
      control values. UT-A1 abundance did not increase in these urea-supplemented rats
      compared with control rats. Additionally, both UT-A2 and UT-B protein abundances
      in the outer medulla increased during urea-induced osmotic diuresis but not in
      NaCl or glucose diuresis. We conclude that during osmotic diuresis, UT-A1
      abundance increases when the percentage of urea in total urinary solute is low
      and UT-A2 and UT-B abundances increase when the urea concentration in the
      medullary interstitium is high. These findings suggest that a reduction in urine
      or interstitial urea results in an increase in UT-A1 protein abundance in an
      attempt to restore inner medullary interstitial urea and preserve urine
      concentrating ability.

PMID- 15251865
TI  - Adipocyte differentiation induces dynamic changes in NF-kappaB expression and
      activity.
AB  - The adipocyte exerts an important role in energy homeostasis, both as depot for
      energy-rich triglycerides and as a source for metabolic hormones. Adipocytes also
      contribute to inflammation and the innate immune response. Although it can be
      physiologically beneficial to combine these two functions in a single cell type
      under some circumstances, the proinflammatory signals emanating from adipocytes
      in the obese state can have local and systemic effects that promote
      atherosclerosis and insulin resistance. The transcriptional machinery in the
      adipocyte that mediates these pro-inflammatory responses has remained poorly
      characterized to date. In particular, no information is currently available on
      the NF-kappaB family of transcription factors. Here, we show that adipogenesis is
      associated with changes in amount and subunit composition of the NF-kappaB
      complexes. NF-kappaB subunits p65 (RelA), p68 (RelB), and IkappaB are upregulated
      during fat cell differentiation. Correspondingly, basal NF-kappaB nuclear gel
      shift and luciferase reporter assays are induced in parallel during
      differentiation. Surprisingly, endotoxin sensitivity of the classical NF-kappaB
      pathway is substantially delayed and attenuated despite increased overall
      inflammatory response in the mature adipocyte, as judged by induction of IL-6 and
      TNF-alpha. As a reflection of the constitutively elevated NF-kappaB activity in
      the mature adipocyte, adipocytes (but not preadipocytes) exert a strong
      inflammatory stimulus on macrophages in vitro, suggesting a cross talk between
      adipocytes and interstitial macrophages in adipose tissue in vivo. These effects
      are mediated by a secretory product of adipocytes that is unlikely to be IL-6 or
      TNF-alpha.

PMID- 15251866
TI  - Muscle glycogen content in type 2 diabetes mellitus.
AB  - Muscle contains the largest reservoir of glycogen (Glyc), a depot that is closely
      regulated and with influence on insulin sensitivity. The current study examines
      muscle Glyc in type 2 diabetes mellitus (T2DM) and obesity and with respect to
      muscle fiber type, intramyocellular lipid content (IMCL), and mitochondrial
      function (oxidative enzyme activity; OX-Enz). There is increasing interest in the
      relation of IMCL and mitochondrial dysfunction with insulin resistance (IR), yet
      the association with muscle Glyc has not been examined with regard to these
      parameters. Using a quantitative histological approach specific to muscle fiber
      types, we assessed muscle Glyc, IMCL, and OX-Enz in vastus lateralis obtained by
      percutaneous biopsy in lean nondiabetic (L; n = 16), obese nondiabetic (Ob; n =
      15), and T2DM volunteers (n = 14). Insulin sensitivity was estimated using
      homeostasis model assessment (HOMA)-IR. Muscle Glyc was reduced in T2DM, a
      deficit evident for type IIa fibers, yet minor in types I and IIb fibers. Low
      Glyc in T2DM correlated with fasting hyperglycemia. Also, in T2DM and Ob, there
      was significantly higher IMCL and lower OX-Enz in all fiber types. The IMCL-to-OX
      Enz ratio, especially for type I fibers, correlated strongly with IR. Similarly,
      a Glyc-to-OX-Enz ratio correlated with IR, particularly for type IIb fibers. This
      ratio tended to be higher in Ob and T2DM. In summary, there is decreased muscle
      Glyc in T2DM yet a disproportional Glyc-to-OX-Enz relationship that is related to
      IR, although not as robustly as the IMCL-to-OX-Enz ratio.

PMID- 15251867
TI  - Physical training may enhance beta-cell function in type 2 diabetes.
AB  - In healthy young subjects, training increases insulin sensitivity but decreases
      the capacity to secrete insulin. We studied whether training changes beta-cell
      function in type 2 diabetic patients. Patients, stratified into "moderate" and
      "low" secretors according to individual C-peptide responses to an intravenous
      glucagon test, were randomly assigned to a training program [ergometer cycling 30
      40 min/day, including at least 20 min at 75% maximum oxygen consumption (Vo(2
      max)), 5 days/wk for 3 mo] or a sedentary schedule. Before and after the
      intervention (16 h after last training bout), a sequential hyperglycemic (90 min
      at 11, 18, and 25 mM) clamp was performed. An intravenous bolus of 5 g of
      arginine was given at the end. Training increased Vo(2 max) 17 +/- 13% and
      decreased heart rate during submaximal exercise (P < 0.05). During the 3 mo of
      sedentary lifestyle, insulin and C-peptide responses to the clamp procedures were
      unchanged in both moderate and low secretors. Likewise, no change in beta-cell
      response was seen after training in the low secretors (n = 5). In contrast,
      moderate secretors (n = 9) showed significant increases in beta-cell responses to
      18 and 25 mM hyperglycemia and to arginine stimulation. Glucagon responses to
      arginine as well as measures of insulin sensitivity and Hb A(1c) levels were not
      altered by training. In conclusion, in type 2 diabetic patients, training may
      enhance beta-cell function if the remaining secretory capacity is moderate but
      not if it is low. The improved beta-cell function does not require changes in
      insulin sensitivity and Hb A(1c) concentration.

PMID- 15251868
TI  - Metabolic adaptations to fasting and chronic caloric restriction in heart,
      muscle, and liver do not include changes in AMPK activity.
AB  - Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a
      central role in allowing cells to adapt to nutrient deprivation in vitro. This
      link between AMPK activity and nutritional status has raised the possibility that
      AMPK plays a role in the metabolic adaptation to acute and chronic nutritional
      stress. However, the effects of nutritional stress on AMPK activity in vivo have
      not been systematically evaluated. To address this, we measured the effects of 24
      h of fasting and 4 mo of caloric restriction (CR) on AMPK alpha 1 and -alpha 2
      activities in heart, skeletal muscle, and liver in mice. Although fasting caused
      the expected changes in body weight, plasma leptin, and free fatty acids, it did
      not increase AMPK activity in heart or skeletal muscle and only increased liver
      AMPK activity by approximately 20% (P = 0.10). Likewise, CR caused the expected
      changes in body weight, plasma leptin, and free fatty acids but did not alter
      AMPK activity in any of the three tissues. Although CR did not alter liver AMPK
      activity, it dramatically decreased the amount of phosphorylated acetyl-CoA
      carboxylase, and this was found to be due to decreased protein expression. Plasma
      leptin, a putative activator of AMPK, varied eightfold across the four groups of
      mice in the absence of changes in AMPK activity in any tissue. We conclude that,
      although the metabolic adaptations to fasting and CR include changes in plasma
      leptin concentration and phosphorylated acetyl-CoA carboxylase, these effects
      occur without changes in AMPK activity.

PMID- 15251869
TI  - Adolescent brain development: a period of vulnerabilities and opportunities.
      Keynote address.
AB  - This article introduces and summarizes the goals of the symposium. It also
      provides an overview of a conceptual framework for understanding adolescence,
      which emphasizes how the very nature of this developmental transition requires an
      interdisciplinary approach-one that focuses on brain/behavior/social-context
      interactions during this important maturational period. More specifically it
      describes a set of neurobehavioral changes that appear to be linked to pubertal
      development, which appear to have a significant effect on motivation and emotion,
      and considers these puberty-specific changes in affect in relation to a much
      larger set of developmental changes in adolescence. This framework is used to
      argue for the need for a transdisciplinary dialogue that brings together work in
      several areas of neuroscience (including animal models) and normal development
      with clinical and social policy research aimed at early intervention and
      prevention strategies.

PMID- 15251870
TI  - Adolescent brain development and animal models.
AB  - Research examining brain development during adolescence is escalating rapidly
      along multiple dimensions, as illustrated by the remarkable diversity of trans
      disciplinary work shown in this symposium. Ontogenetic transitions
      characteristics of adolescence are common among mammalian species. Although no
      other species demonstrates the full complexity of brain and behavioral function
      seen in human adolescents, adolescence appears to be a highly conserved
      developmental stage, its characteristics sculpted to meet common evolutionary
      pressures that include the avoidance of inbreeding at this time of sexual
      emergence. Numerous similarities are found between human adolescents and
      adolescents of other species in terms of developmental history and genetic
      constraints, as well as neurobehavioral and physiological characteristics. These
      similarities provide face and construct validity to support use of animal models
      as tools for the study of adolescence and the unique opportunities and
      vulnerabilities afforded by this developmental transition.

PMID- 15251871
TI  - Risk taking and novelty seeking in adolescence: introduction to part I.
AB  - Risk taking and novelty seeking are hallmarks of typical adolescent behavior.
      Adolescents seek new experiences and higher levels of rewarding stimulation, and
      often engage in risky behaviors, without considering future outcomes or
      consequences. These behaviors can have adaptive benefits with regard to the
      development of independence and survival without parental protection, but also
      render the adolescent more vulnerable to harm. Indeed, the risk of injury or
      death is higher during the adolescent period than in childhood or adulthood, and
      the incidence of depression, anxiety, drug use and addiction, and eating
      disorders increases. Brain pathways that play a key role in emotional regulation
      and cognitive function undergo distinct maturational changes during this
      transition period. It is clear that adolescents think and act differently from
      adults, yet relatively little is known about the precise mechanisms underlying
      neural, behavioral, and cognitive events during this period. Increased
      investigation of these dynamic alterations, particularly in prefrontal and
      related corticolimbic circuitry, may aid this understanding. Moreover, the
      investigation of mammalian animal models of adolescence-such as those examining
      impulsivity, reward sensitivity, and decision making-may also provide new
      opportunities for addressing the problem of adolescent vulnerability.

PMID- 15251873
TI  - Risk taking in adolescence: what changes, and why?
AB  - Extant studies of age differences in cognitive processes relevant to risk taking
      and decision making, such as risk perception and risk appraisal, indicate few
      significant age differences in factors that might explain why adolescents engage
      in more risk taking than adults. The present analysis suggests that the greater
      propensity of adolescents to take risks is not due to age differences in risk
      perception or appraisal, but to age differences in psychosocial factors that
      influence self-regulation. It is argued that adolescence is a period of
      heightened vulnerability to risk taking because of a disjunction between novelty
      and sensation seeking (both of which increase dramatically at puberty) and the
      development of self-regulatory competence (which does not fully mature until
      early adulthood). This disjunction is biologically driven, normative, and
      unlikely to be remedied through educational interventions designed to change
      adolescents' perception, appraisal, or understanding of risk. Interventions
      should begin from the premise that adolescents are inherently more likely than
      adults to take risks, and should focus on reducing the harm associated with risk
      taking behavior.

PMID- 15251872
TI  - Limbic corticostriatal systems and delayed reinforcement.
AB  - Impulsive choice, one aspect of impulsivity, is characterized by an abnormally
      high preference for small, immediate rewards over larger delayed rewards, and can
      be a feature of adolescence, but also attention-deficit/hyperactivity disorder
      (ADHD), addiction, and other neuropsychiatric disorders. Both the serotonin and
      dopamine neuromodulator systems are implicated in impulsivity; manipulations of
      these systems affect animal models of impulsive choice, though these effects may
      depend on the receptor subtype and whether or not the reward is signaled. These
      systems project to limbic cortical and striatal structures shown to be abnormal
      in animal models of ADHD. Damage to the nucleus accumbens core (AcbC) causes rats
      to exhibit impulsive choice. These rats are also hyperactive, but are unimpaired
      in tests of visuospatial attention; they may therefore represent an animal model
      of the hyperactive-impulsive subtype of ADHD. Lesions to the anterior cingulate
      or medial prefrontal cortex, two afferents to the AcbC, do not induce impulsive
      choice, but lesions of the basolateral amygdala do, while lesions to the
      orbitofrontal cortex have had opposite effects in different tasks measuring
      impulsive choice. In theory, impulsive choice may emerge as a result of abnormal
      processing of the magnitude of rewards, or as a result of a deficit in the
      effects of delayed reinforcement. Recent evidence suggests that AcbC-lesioned
      rats perceive reward magnitude normally, but exhibit a selective deficit in
      learning instrumental responses using delayed reinforcement, suggesting that the
      AcbC is a reinforcement learning system that mediates the effects of delayed
      rewards.

PMID- 15251874
TI  - High-risk behavior during adolescence: comments on part I.
AB  - Cardinal and Steinberg provide evidence from both laboratory animal and human
      studies indicating that behavior is controlled by two distinct brain systems, one
      activational and the other inhibitory. This conceptual framework continues to be
      a useful integrative framework in developmental neurobiology and psychology.
      Despite the conceptual framework that posits a two-system control of high-risk
      behavior, it is notable that the bulk of research related to this topic has
      focused on one system in isolation from the other. Since the activational and
      inhibitory systems are constructs that are amenable to investigation using both
      laboratory animals and human subjects, it seems that a fruitful avenue for future
      interdisciplinary research would be to ascertain the interactive effect of these
      systems across the periadolescent period.

PMID- 15251875
TI  - Integrating research on developmental psychopathology and neuroscience in the
      study of adolescence: introduction to part II.
AB  - This chapter introduces three papers that summarize research findings in clinical
      and basic neuroscience. They integrate prior research on clinical aspects of
      developmental psychopathology, basic research on brain development in nonhuman
      primates, and neuroimaging research on both normal and abnormal human
      development. From the clinical perspective these papers call attention to the
      unique relationship between adolescence and psychopathology. From the basic
      science perspective they call attention to the sequence of events that culminates
      in a fully mature central nervous system.

PMID- 15251876
TI  - Postnatal development of prefrontal inhibitory circuits and the pathophysiology
      of cognitive dysfunction in schizophrenia.
AB  - The typical appearance of the clinical features of schizophrenia during late
      adolescence or early adulthood suggests that adolescence-related
      neurodevelopmental events may contribute to the pathophysiology of this disorder.
      Here the role that GABA-mediated inhibition in the dorsal lateral prefrontal
      cortex (DLPFC) plays in regulating working memory, a core cognitive process that
      matures late and that is disturbed in schizophrenia, is reviewed. Recent studies
      are summarized that demonstrate (1) that certain pre- and postsynaptic markers of
      GABA neurotransmission in the monkey DLPFC exhibit striking changes during
      adolescence, and (2) that these same markers are markedly altered in the DLPFC of
      subjects with schizophrenia. The implications of these findings for treatment and
      prevention strategies are discussed.

PMID- 15251877
TI  - Structural magnetic resonance imaging of the adolescent brain.
AB  - Magnetic resonance imaging (MRI) provides accurate anatomical brain images
      without the use of ionizing radiation, allowing longitudinal studies of brain
      morphometry during adolescent development. Results from an ongoing brain imaging
      project being conducted at the Child Psychiatry Branch of the National Institute
      of Mental Health indicate dynamic changes in brain anatomy throughout
      adolescence. White matter increases in a roughly linear pattern, with minor
      differences in slope in the four major lobes (frontal, parietal, temporal,
      occipital). Cortical gray matter follows an inverted U-shape developmental course
      with greater regional variation than white matter. For instance, frontal gray
      matter volume peaks at about age 11.0 years in girls and 12.1 years in boys,
      whereas temporal gray matter volume peaks at about age at 16.7 years in girls and
      16.2 years in boys. The dorsal lateral prefrontal cortex, important for
      controlling impulses, is among the latest brain regions to mature without
      reaching adult dimensions until the early 20s. The details of the relationships
      between anatomical changes and behavioral changes, and the forces that influence
      brain development, have not been well established and remain a prominent goal of
      ongoing investigations.

PMID- 15251878
TI  - Neuroimaging of developmental psychopathologies: the importance of self
      regulatory and neuroplastic processes in adolescence.
AB  - Normal brain maturational and developmental processes, together with plastic
      reorganization of the brain in response to experiential demands, contribute to
      the acquisition of improved capacities for self-regulation and impulse control
      during adolescence. The frontal lobe is a main focus for these developmental and
      plastic processes during the transition from adolescence into adulthood. Tourette
      syndrome (TS), defined as the chronic presence of motor and vocal tics, has been
      increasingly conceptualized as a disorder of impaired self-regulatory control.
      This disordered control is thought to give rise to semicompulsory urges to
      perform the movements that constitute simple tics, complex tics, or compulsions.
      Neuroimaging studies suggest that the expression of the genetic diathesis to TS
      is influenced by genetic and nongenetic factors affecting activity-dependent
      reorganization of neuroregulatory systems, thereby influencing the phenotype,
      illness severity, and adult outcome of tic disorders. Similar developmental
      processes during adolescence likely determine the phenotype and natural history
      of a broad range of other complex neuropsychiatric disorders of childhood onset,
      and they likely contribute to the acquisition of improved self-regulatory
      capacities that characterize normal adolescent development.

PMID- 15251879
TI  - Brain development during puberty and adolescence: comments on part II.

PMID- 15251880
TI  - Interrelationships between hormones, behavior, and affect during adolescence:
      understanding hormonal, physical, and brain changes occurring in association with
      pubertal activation of the reproductive axis. Introduction to part III.
AB  - This paper summarizes the goals of this section and considers current knowledge
      about the association between hormonal changes that occur over pubertal
      development and the changes in behavior and brain function over the adolescent
      period. It reviews the cascade of neural and hormonal changes that occur with
      puberty; discusses mechanisms by which these changes can affect higher-order
      brain processes; reviews the current limited state of knowledge about links
      between puberty and changes in affect regulation in the adolescent period;
      identifies hurdles that have made progress in our understanding of these
      relationships difficult; and suggests areas for future investigation that will
      allow us to obtain a much more comprehensive understanding of these
      interrelationships. This overview of the physiological processes occurring at
      puberty indicates that puberty (1) encompasses changes in a number of neural
      systems; (2) results in altered secretion of a number of hormones; (3) involves
      hormones that are secreted in a pulsatile manner so that collection of a single
      blood sample does not clearly delineate hormone profiles; and (4) shows
      considerable individual variation in the rate of progression and in hormone
      secretion during progression. The important role that gonadal steroid hormones
      play throughout development and adulthood in regulating plastic changes in
      neuronal structure and function is noted, highlighting the need for further
      studies to determine the extent to which the dramatic increases in circulating
      steroid hormones at puberty modulate brain circuits that underlie changes in
      social behaviors, risk-taking behaviors, and cognitive function at adolescence.

PMID- 15251881
TI  - Puberty, ovarian steroids, and stress.
AB  - Puberty is accompanied by a number of changes, among them increased risk for
      development of major depression. The most common etiology of major depression is
      stressful life events, being present in approximately 90% of first episodes of
      depression. The hypothalamic-pituitary-adrenal (HPA) axis is one of the major
      systems involved in responses to stress, and this system is clearly influenced by
      ovarian hormones. Normal women demonstrate resistance to negative feedback of
      both cortisol in the fast-feedback paradigm and dexamethasone in the standard
      delayed-feedback paradigm. Depressed premenopausal women show greater increases
      in baseline cortisol than postmenopausal depressed women and than depressed men.
      Studies in rodents suggest a similar resistance to glucocorticoid feedback but
      suggest that estradiol can function to inhibit stress responsiveness. Studies of
      premenopausal depressed women demonstrate lower estradiol, which suggests that
      there is less inhibitory feedback of estradiol on the HPA axis, while normal
      progesterone continues to augment stress responses further. The onset of these
      reproductive hormonal changes modulating stress systems at puberty may sensitize
      girls to stressful life events, which become more frequent at the transition to
      puberty and young adulthood.

PMID- 15251882
TI  - Interrelationships between hormones, behavior, and affect during adolescence:
      complex relationships exist between reproductive hormones, stress-related
      hormones, and the activity of neural systems that regulate behavioral affect.
      Comments on part III.
AB  - Adolescence is a period in life marked by change, encompassing physiological
      changes associated with pubertal development, changes in social status and the
      social stresses that an individual faces, and changes in behavioral affect
      regulation. The interactions between activity in the reproductive axis, the
      neural systems that regulate stress, hormones produced in response to stress, and
      neural systems governing behavioral affect regulation are complex and
      multifaceted. Although our understanding of these interactions remains
      rudimentary, we do know that stress can suppress activity of the reproductive
      axis, that reproductive hormones can modulate the activity of neural systems that
      govern the body's responses to stress, that both reproductive function and stress
      responsiveness can be altered in depressed individuals, and that the function of
      some of the key neural systems regulating behavioral affect (i.e., serotonergic,
      noradrenergic, dopaminergic systems) are modulated by both gonadal steroid
      hormones and adrenal steroid hormones. This summary reviews the central
      interactions discussed in this session on the interrelationships between
      hormones, behavior, and affect during adolescence and identifies key topics that
      require further investigation in order to understand the role that pubertal
      changes in reproductive function, interacting with increased exposure to life
      stresses, play in modulating behavioral affect regulation during the adolescent
      period.

PMID- 15251883
TI  - Adolescence: vulnerable period for stress-induced prefrontal cortical function?
      Introduction to part IV.
AB  - Exposure to even mild uncontrollable stress impairs the cognitive functioning of
      the prefrontal cortex, a brain region critical for insight, judgment, and the
      inhibition of inappropriate behaviors. Several neurobiological factors may
      contribute to an exaggeration of the stress response in adolescence, for example,
      an increased dopaminergic projection to prefrontal cortex, and in females,
      increased circulating estrogen, as estrogen amplifies many aspects of the stress
      response and lowers the threshold for stress-induced prefrontal cortical
      dysfunction. These neurobiological factors may increase susceptibility to
      impaired judgment, drug addiction, and neuropsychiatric disorders during
      adolescence.

PMID- 15251884
TI  - Adolescent development of forebrain stimulant responsiveness: insights from
      animal studies.
AB  - Although initiation of drug abuse occurs primarily during adolescence, little is
      known about the central effects of nicotine and other abused drugs during this
      developmental period. Here evidence, derived from studies in rodents, is
      presented that suggests that tobacco use initiation during early adolescence
      results from a higher reward value of nicotine. The developmental profiles of the
      rewarding effects of other abused drugs, such as cocaine, differ from that of
      nicotine. Using in situ hybridization to quantify mRNA levels of the immediate
      early gene, cfos, the neuronal activating effects of nicotine in limbic and
      sensory cortices at different developmental stages are evaluated. Significant age
      changes in basal levels of cfos mRNA expression in cortical regions are observed,
      with a peak of responding of limbic cortices during early adolescence. A changing
      pattern of nicotine-induced neuronal activation is seen across the developmental
      spectrum, with unique differences in both limbic and sensory cortex responding
      during adolescence. An attentional set-shifting task was also used to evaluate
      whether the observed differences during adolescence reflect early functional
      immaturity of prefrontal cortices that regulate motivated behavior and
      psychostimulant responding. The finding of significantly better responding during
      adolescence suggests apparent functional maturity of prefrontal circuits and
      greater cognitive flexibility at younger ages. These findings in rodent models
      suggest that adolescence is a period of altered sensitivity to environmental
      stimuli, including abused drugs. Further efforts are required to overcome
      technical challenges in order to evaluate drug effects systematically in this age
      group.

PMID- 15251885
TI  - The adolescent brain: excuse versus explanation: comments on part IV.

PMID- 15251886
TI  - The importance of adolescence in the development of nicotine dependence:
      introduction to part V.
AB  - This article sets the stage for the papers in Part V by describing the research
      work of the Tobacco Etiology Research Network (TERN), an initiative of the Robert
      Wood Johnson Foundation. Two studies coming from this matrix include one on the
      acquisition of tobacco use and another on the trajectories of tobacco use among
      college freshman.

PMID- 15251887
TI  - Nicotine withdrawal in adolescent and adult rats.
AB  - Previous research with animal models has demonstrated that adolescent rats
      display heightened sensitivity to the reinforcing and stimulant effects of
      nicotine relative to adult rats. Little work has focused on the response of
      adolescent rats to measures of nicotine withdrawal. To test the hypothesis that
      adolescent rats may be differentially sensitive to withdrawal relative to their
      adult counterparts, the present study was designed to compare precipitated
      withdrawal in adolescent and adult rats following chronic nicotine
      administration. Adult and adolescent rats were prepared with subcutaneous osmotic
      minipumps that delivered either saline or nicotine (9 mg/kg per day, salt; N =12
      per group). All rats were challenged with the nicotinic receptor antagonist
      mecamylamine (1.5 mg/kg) on day 7 of chronic nicotine treatment. Twenty minutes
      after the injection, overt somatic signs of withdrawal (i.e., eye blinks,
      writhes, body shakes, teeth chatter, gasps, and ptosis) were recorded for 10 min.
      Adult rats were observed on postnatal day 73-77, and adolescent rats were tested
      on postnatal day 36-40. The results revealed a robust increase in mecamylamine
      induced withdrawal signs in adult rats receiving chronic nicotine relative to
      adult rats receiving saline. In contrast, mecamylamine did not precipitate
      withdrawal signs in adolescent rats receiving chronic nicotine. These results
      indicate that there is decreased sensitivity to the somatic aspects of nicotine
      withdrawal in adolescent rats that may maximize the reinforcing effects of
      nicotine during adolescence by minimizing the aversive effects of abstinence.

PMID- 15251888
TI  - Individual and contextual influences on adolescent smoking.
AB  - Cigarette smoking among adolescents remains one of the most important public
      health challenges. Despite much attention to research on the etiology of smoking,
      notably the examination of factors that differentiate adolescent smokers from
      never smokers, much less is known about factors that predict the development of
      dependence once an adolescent tries smoking. This paper reviews individual and
      contextual influences on the progression of smoking among adolescents. Highlights
      include a consideration of multiple levels of influence, from intra-individual
      factors, such as genetics, demographics, temperament and comorbidities, to social
      influences, such as families and peers, to the more macro, societal/cultural
      levels of influence, including advertising and tobacco-related policies. More
      recent work examining microcontextual influences through the use of Ecological
      Momentary Assessments is also discussed. Finally, the need to consider both
      developmental and transdisciplinary approaches to understanding the development
      of nicotine dependence in adolescents is emphasized.

PMID- 15251889
TI  - The importance of adolescence in the development of nicotine dependence: comments
      on part V.

PMID- 15251890
TI  - Adolescence and the trajectory of alcohol use: introduction to part VI.
AB  - Research in the area of adolescent alcohol use is progressing rapidly, as
      exemplified by the chapters in this section. Basic animal research in rodents has
      revealed adolescents to be more sensitive than adults to ethanol-induced
      disruptions in brain plasticity, although adolescents conversely are relatively
      insensitive to ethanol cues that serve to moderate intake. Risks for excessive
      alcohol consumption due to genetic background have been shown in primate research
      to be exacerbated by adverse early life experiences. Studies in clinical
      populations have revealed neurocognitive deficits evident years following
      adolescent alcohol abuse, along with evidence that some neural changes may
      predate adolescent alcohol abuse, whereas others appear to be a consequence of
      this abuse. Further research is needed to detail determinants and consequences of
      adolescent alcohol abuse and to identify potential protective factors to diminish
      the propensity for excessive use of alcohol during this critical developmental
      period.

PMID- 15251891
TI  - Hippocampal function during adolescence: a unique target of ethanol effects.
AB  - Behaviors mediated by the hippocampus have long been known to be sensitive to the
      acute, chronic, and prenatal effects of ethanol. It has recently become clear
      that hippocampal function is uniquely responsive to ethanol during periadolescent
      development, and that alcohol affects behavior and brain function differently in
      adolescents and adults. We have used behavioral techniques, as well as
      extracellular and whole-cell electrophysiological techniques, to assess the
      effects of acute and chronic ethanol exposure on hippocampal function during
      adolescence and adulthood. Our results are consistent with the view that the
      hippocampus is more sensitive to the acute effects of ethanol during adolescence
      and may be more susceptible to the neurotoxic effects of ethanol during this
      developmental period. Studies of this type have yielded valuable information for
      prevention, education, and public policy efforts related to underage drinking.

PMID- 15251892
TI  - The use of adolescent nonhuman primates to model human alcohol intake:
      neurobiological, genetic, and psychological variables.
AB  - Traits characteristic of type I and type II alcoholism are thought to relate to
      dysregulated central nervous system serotonin functioning. In this review, we
      discuss variables associated with high adolescent alcohol consumption and other
      risk-taking behaviors in a nonhuman primate model. Adolescent primates with low
      CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and
      exhibit increased levels of alcohol consumption. Both genetic and environmental
      factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence
      variation within serotonin system genes, for example, a repeat polymorphism in
      the transcriptional control region of the monoamine oxidase gene (MAOA-LPR),
      increases the propensity for adolescent males to consume alcohol. Environmental
      factors, such as early life stress in the form of peer-rearing or early age of
      exposure to alcohol, are also associated with increased alcohol consumption. Peer
      reared females, especially those exposed to alcohol during early adolescence,
      exhibit increased rates of alcohol consumption compared to those exposed to
      alcohol later in development. When genetic variables are also considered, there
      is an interaction between the low activity serotonin transporter gene promoter s
      allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but
      not males, suggesting that the interactions between genes and the environment may
      be sexually dichotomous. By learning more about the interactions between genes,
      early experience, and alcohol intake in the adolescent nonhuman primate, we may
      be able to identify factors that contribute to the susceptibility, pathogenesis,
      and progression of impulse control disorders, such as alcoholism.

PMID- 15251893
TI  - Adolescence and the trajectory of alcohol use: basic to clinical studies.
AB  - Emerging findings from developmentally focused research indicates subtle but
      important neurocognitive disadvantages among adolescents with alcohol-use
      disorders (AUD) as compared to teens without AUD. Even after 3 weeks of
      abstinence AUD youth display a 10% decrement in delayed memory functions.
      Neuropsychological testing of youth followed at 4 and 8 years demonstrates that
      heavy drinking during adolescence is associated with diminished retrieval of
      verbal and nonverbal material, and poorer performance on tests requiring
      attention skills. Alcohol withdrawal over the teen years appears to uniquely
      contribute to deterioration in functioning in visuospatial tasks. Brain imaging
      studies suggest reduced hippocampal volumes, white matter microstructure
      irregularities, brain response abnormalities while performing challenging
      cognitive tasks, and enhanced brain response when viewing alcohol cues (i.e.,
      alcohol advertisements) among adolescents with AUD. Family characteristics such
      as history of alcoholism and socioeconomic status as well as personal features,
      including adolescent psychopathology, gender, and age of onset must be carefully
      considered when investigating the influence of teenage drinking on
      neurocognition. Further research is needed to understand how age at onset of
      drinking and duration of abstinence at the time of assessment affect cognitive
      findings. Longitudinal studies are needed to clarify neuromaturational changes
      associated with early alcohol exposure and patterns of resiliency. Although the
      magnitude of alcohol-related effects observed in adolescents' neurocognition is
      relatively modest, the implications are major given the prevalence of alcohol
      involvement, and the important educational, occupational, and social transitions
      that occur during adolescence.

PMID- 15251894
TI  - Trajectories of alcohol use and electrophysiological and morphological indices of
      brain development: distinguishing causes from consequences.
AB  - Alcoholism is a major public health problem. Patterns of drinking during
      adolescence can influence the likelihood of this outcome. Both environmental
      variation and familial/genetic susceptibility play important roles in this
      process. While there is some evidence to suggest that metabolic factors play a
      role in whether some individuals are protected from developing alcohol problems,
      there is substantial reason to look for cognitive factors that are associated
      with increased susceptibility. Developmental trajectories for information
      processing that can be reflected in P300 amplitude changes over time, as well as
      trajectories describing acquisition of postural control when compared in
      offspring from families with multiple cases of alcoholism or those with none or
      few, suggest that brain development provides a clue to why some individuals are
      more susceptible to becoming alcoholic. Finally, differences seen in amygdala
      volume between high- and low-risk adolescents suggest that functional differences
      seen in electrophysiological responding or neuropsychological test performance
      may have anatomical correlates.

PMID- 15251895
TI  - Regulation of sleep and arousal: introduction to part VII.
AB  - This paper introduces the theme of the relationship between sleep deprivation and
      behavior.

PMID- 15251896
TI  - Pubertal development of sex differences in circadian function: an animal model.
AB  - The development of adult circadian function, particularly sexual dimorphism of
      function, has been well studied only in rapidly developed rodents. In such
      species development is complete by weaning. Data from adolescent humans suggest
      that significant development occurs during the pubertal period. We hypothesized
      that a more slowly developing rodent might better mimic the changes in circadian
      function around puberty in humans and allow us to determine the underlying neural
      changes. Entrained and free-running circadian rhythms were analyzed and
      correlated with pubertal development in male and female Octodon degus (degu) that
      remained gonadally intact or were gonadectomized at weaning. Brains were
      collected during development to measure androgen and estrogen receptors in the
      suprachiasmatic nuclei (SCN) Adult circadian period does not develop until 10-12
      months of age in degus, long after the onset of gonadal maturation (3-5 months).
      The timing of circadian period maturation correlates with the appearance of
      steroid receptors in the SCN. Changes in free-running rhythms only occurred in
      gonadally intact degus. Adult phase angles of activity onset develop between 2
      and 3 months of age (comparing results of two experiments), soon after the onset
      of pubertal changes. CONCLUSION: The development of sexually dimorphic adult
      circadian period occurs after gonadal puberty is complete and requires the
      presence of gonadal steroids. The delay in development until after gonadal
      puberty is likely due to the delayed appearance of steroid receptors in the SCN.
      Phase is not sexually dimorphic and changes in the absence of steroid hormones.

PMID- 15251897
TI  - Regulation of adolescent sleep: implications for behavior.
AB  - Adolescent development is accompanied by profound changes in the timing and
      amounts of sleep and wakefulness. Many aspects of these changes result from
      altered psychosocial and life-style circumstances that accompany adolescence. The
      maturation of biological processes regulating sleep/wake systems, however, may be
      strongly related to the sleep timing and amount during adolescence-either as
      "compelling" or "permissive" factors. The two-process model of sleep regulation
      posits a fundamental sleep-wake homeostatic process (process S) working in
      concert with the circadian biological timing system (process C) as the primary
      intrinsic regulatory factors. How do these systems change during adolescence? We
      present data from adolescent participants examining EEG markers of sleep
      homeostasis to evaluate whether process S shows maturational changes permissive
      of altered sleep patterns across puberty. Our data indicate that certain aspects
      of the homeostatic system are unchanged from late childhood to young adulthood,
      while other features change in a manner that is permissive of later bedtimes in
      older adolescents. We also show alterations of the circadian timing system
      indicating a possible circadian substrate for later adolescent sleep timing. The
      circadian parameters we have assessed include phase, period, melatonin secretory
      pattern, light sensitivity, and phase relationships, all of which show evidence
      of changes during pubertal development with potential to alter sleep patterns
      substantially. However the changes are mediated-whether through process S,
      process C, or by a combination-many adolescents have too little sleep at the
      wrong circadian phase. This pattern is associated with increased risks for
      excessive sleepiness, difficulty with mood regulation, impaired academic
      performance, learning difficulties, school tardiness and absenteeism, and
      accidents and injuries.

PMID- 15251898
TI  - Regulation of sleep and arousal: comments on part VII.
AB  - This paper links the papers in this session and describes briefly how together
      they represent an ideal example of the kind of trans-disciplinary approach to
      understanding aspects of adolescent maturation that can have major clinical and
      social policy implications. The issues of adolescent sleep needs, circadian
      changes linked to pubertal maturation, the effects of sleep deprivation on
      adolescent health and behavior, and social controversies such as delaying the
      start times of high schools to address the problems of adolescent sleep
      deprivation all point to the need for additional empirical studies. This will
      require studies of normal human development as well as animal models to
      investigate the mechanisms underpinning these developmental changes in sleep and
      circadian regulation.

PMID- 15251899
TI  - Adolescent development and the regulation of behavior and emotion: introduction
      to part VIII.
AB  - This article introduces and identifies key issues in the articles in this
      section.

PMID- 15251900
TI  - The emergence of collaborative brain function: FMRI studies of the development of
      response inhibition.
AB  - Adolescence marks the beginning of adult-level cognitive control of behavior
      supported by the brain maturation processes of synaptic pruning and myelination.
      Cognitive development studies on adolescence indicate that this period is
      characterized by improvements in the performance of existing abilities including
      speed and capacity of information processing and the ability to have consistent
      cognitive control of behavior. Although adolescents can behave at adult levels in
      some ways, brain imaging studies indicate that the functional organization of
      brain systems that support higher-cognitive processes are not fully mature.
      Synaptic pruning allows for more efficient local computations, enhancing the
      ability of discrete brain regions to support high-level cognitive control of
      behavior including working memory. Myelination increases the speed of neuronal
      transmission supporting the collaboration of a widely distributed circuitry,
      integrating regions that support top-down cognitive control of behavior.
      Functional brain imaging methods allow for the characterization of the
      relationship between cognitive development and brain maturation as we can map
      progressions in the establishment of distributed brain circuitry and its relation
      to enhanced cognitive control of behavior. We present a review on the maturation
      (as distinct from "development" in emphasizing the transition to maturity and
      stabilization) of response inhibition, brain structure, and brain function
      through adolescence. We also propose a model for brain-behavior maturation that
      allows for the qualitative changes in cognitive processes that occur during
      adolescence.

PMID- 15251901
TI  - Regulatory processes, risk, and resilience in adolescent development.
AB  - This article highlights the potential of developmental psychopathology as a
      useful integrative perspective for the challenging task of linking the study of
      brain development and adolescent behavior in context; it considers clues from
      behavioral research on resilience on the nature of regulatory processes as risks
      and assets, or vulnerabilities and protective factors for the development of
      competence and psychopathology in adolescence; and it advocates more integrative
      neurobehavioral research on risk and resilience in adolescent development.

PMID- 15251902
TI  - Adolescent development and the regulation of behavior and emotion: comments on
      part VIII.

PMID- 15251904
TI  - Development of error-monitoring event-related potentials in adolescents.
AB  - In order to study the maturation of neurobehavioral systems involved in affect
      regulation and behavioral choices during adolescence, we examined brain activity
      associated with response monitoring and error detection using event-related
      potentials (ERPs). In a visual flanker test, trials with incorrect responses
      elicit ERP components including an error-related negativity (ERN) and a later
      error-positivity (Pe). We examined the amplitude and latency of the ERN and Pe of
      incorrect responses in 124 children from 7 to 18 years of age. The ERN amplitude
      in error trials increased with age although this was qualified by a nonlinear
      change. The quadratic distribution of the ERN indicated an initial drop in
      amplitude (lowest at age 10 for girls; age 13 for boys) with a subsequent rise
      through adolescence. The Pe amplitude did not change with age. Results are
      discussed with respect to continued maturation of the anterior cingulate cortex
      and possible influences on adolescent behaviors.

PMID- 15251905
TI  - ERP correlates of action monitoring in adolescence.
AB  - This study examines the development of action monitoring in adolescence by
      measuring the N200, the ERN (error-related negativity) and the P(E) (error
      positivity), which are event-related potentials (ERPs) that appear to be
      generated in the anterior cingulate cortex (ACC) and reflect action-monitoring
      processes. We predicted that amplitude would be significantly greater in late
      compared to early adolescence. Participants consisted of 11 adolescents that were
      divided into early (age 9-14) and late (age 14-17) adolescence groups. ERPs were
      recorded during an 840-trial arrow-flanker task and using 128-channel dense array
      EEG. Results indicated that there were no differences in P(E) amplitude but that
      N200 and ERN amplitudes were greater in the late adolescence group. According to
      the conflict monitoring hypothesis, this suggests that the ability to detect
      error-related conflict, which is involved in the modulation of cognitive control,
      appears to be fully developed later in adolescence and may be linked to the
      maturation of the ACC.

PMID- 15251906
TI  - Individual differences in executive attention predict self-regulation and
      adolescent psychosocial behaviors.
AB  - This study examined temperament, executive attention, parental monitoring and
      relationships, and involvement in pro- and antisocial behaviors in an ethnically
      diverse sample of adolescents. We sought to relate parent- and self-reported
      effortful control to performance on measures of executive attention and to better
      understand the relative contributions of individual-difference variables and
      environmental variables in predicting behaviors in adolescence. The results
      indicated a relationship between poor executive attention and mother-reported
      effortful control. Inclusion of individual-difference variables significantly
      increased prediction of problem-behavior scores, suggesting the importance of
      including such variables in studies of adolescent deviance.

PMID- 15251907
TI  - Positive and negative affect in depression: influence of sex and puberty.
AB  - To examine adolescent depression as a model for unusual emotion regulation, the
      current study considered the influence of gender, pubertal development, and
      cortisol on self-reported mood. Children and adolescents with major depressive
      disorder (n = 35, mean age 12.5 years) were compared with psychiatrically healthy
      children and adolescents (n = 36, mean age 10.5 years). During a three-day
      assessment, participants rated their mood at three time points, pubertal
      development was determined through physical examination, and plasma cortisol was
      sampled during the second night. Depressed participants experienced less positive
      affect and more negative affect than did controls. Diagnostic group, gender, and
      pubertal status interacted to predict negative affect, with depressed adolescent
      girls experiencing especially high levels of negative affect. Cortisol was
      generally unrelated to depression and mood. Findings are consistent with emotion
      based models of depression and with the literature on depression and emotion
      regulation during adolescence.

PMID- 15251908
TI  - Sex differences in the effects of pubertal development on responses to a
      corticotropin-releasing hormone challenge: the Pittsburgh psychobiologic studies.
AB  - We propose that sex differences in HPA regulation may emerge during puberty and
      help to explain sex differences in depression. In this study, we examined sex
      differences in cortisol responses to CRH challenge across pubertal stages in
      carefully screened control subjects from the Pittsburgh Psychobiologic Studies.
      Participants were 7-16 years of age, physically healthy, and had no personal or
      family history of psychiatric disorder. Physician-rated Tanner staging was
      conducted, followed by CRH challenge sessions including 30-40 minutes pre
      infusion baseline, 1 microg/kg CRH infusion, 90-180 minutes of post-infusion
      measures, and 9-10 plasma cortisol samples. Girls showed increasing total
      cortisol responses to CRH across Tanner stages, explained by slower recovery from
      peak cortisol levels, while boys showed similar total responses across Tanner
      stages. Results show subtle sex differences in the influence of puberty on HPA
      regulation at the pituitary level, which may represent one factor underlying the
      emergence of girls' greater rates of depression during this time.

PMID- 15251909
TI  - Sleep hygiene and sleep quality in Italian and American adolescents.
AB  - This study investigated cross-cultural differences in adolescent sleep hygiene
      and sleep quality. Participants were 1348 students (655 males; 693 females) aged
      12-17 years from public school systems in Rome, Italy (n = 776) and Southern
      Mississippi (n = 572). Participants completed the Adolescent Sleep-Wake Scale and
      the Adolescent Sleep Hygiene Scale. Reported sleep hygiene and sleep quality were
      significantly better for Italian than American adolescents. A moderate linear
      relationship was observed between sleep hygiene and sleep quality in both samples
      (Italians: R =.40; Americans: R =.46). Separate hierarchical multiple regression
      analyses showed that sleep hygiene accounted for significant variance in sleep
      quality, even after controlling for demographic and health variables (Italians:
      R(2) =.38; Americans: R(2) =.44). The results of this study suggest that there
      are cultural differences in sleep quality and sleep hygiene practices, and that
      sleep hygiene practices are importantly related to adolescent sleep quality.

PMID- 15251910
TI  - Cognitive and emotional components of frontal lobe functioning in childhood and
      adolescence.
AB  - Frontal lobe functions include a range of cognitive, emotional, and social
      abilities that enable goal-directed behavior. Although a number of studies have
      plotted the development of frontal lobe functions in childhood, few have extended
      into the adolescent years. There is also little information on which cognitive
      and emotional components of frontal functioning may be correlated. The aims of
      this study were to identify and compare age effects on different components of
      frontal functioning in childhood and adolescence and to examine whether abstract
      reasoning skills were associated with levels of emotional intelligence and social
      sensitivity. Twenty children (ages 9-18) were recruited from the local community
      for a study of normal adolescent brain development. All subjects were free of
      psychiatric or developmental disorders, as determined by a structured interview.
      Subjects completed a comprehensive neuropsychological test battery, as well as
      self-report measures of social sensitivity (anxiety) and emotional intelligence.
      Significant age effects were found for measures of abstract reasoning, response
      inhibition, and attentional set shifting. Levels of social anxiety increased
      moderately with age, although not significantly at this sample size. Abstract
      reasoning skills correlated positively with levels of social anxiety but not
      emotional intelligence. The pattern of results suggests differential
      developmental trajectories across various cognitive and emotional domains of
      frontal lobe functioning in childhood and adolescence. Increased abstract
      reasoning ability may be associated with increased vulnerability to social
      anxiety during this period.

PMID- 15251911
TI  - Trajectories of adolescent emotional and cognitive development: effects of sex
      and risk for drug use.
AB  - Adolescence has been widely accepted as a time for notable alterations in brain
      functioning. The objective of this longitudinal study was to compare trajectories
      of emotional and cognitive development in adolescent girls and boys with low-
      versus high-risk for future drug use. Nineteen healthy adolescents (aged 13.9 +/-
      2.0 years; 10 girls), stratified into low- and high-risk groups based on family
      history of drug abuse, were examined at baseline and after one year. Emotional
      intelligence was assessed using the Bar-On Emotional Quotient Inventory, the
      Multidimensional Anxiety Scale for Children, and the Perceived Stress Scale. The
      neurocognitive test battery was designed to evaluate academic achievement,
      executive function, verbal memory and learning, and included the Wide Range
      Achievement Test, Stroop Color-Word Interference Test, Rey Auditory Verbal
      Learning Test, and Digit Span and Digit Symbol subtests of the Wechsler Adult
      Intelligence Scale-Revised. Improvements in academic achievement, executive
      function, and working memory were observed at the one-year follow-up. Notable sex
      differences also were evident in emotional intelligence, academic achievement,
      and memory. Interestingly, these sex-related differences interacted with risk
      status; improvement in cognitive performance in boys and low-risk girls was
      generally superior to high-risk girls, who tended to show modest, if any,
      improvement at the one-year follow-up. These preliminary findings provide
      evidence of sex differences in emotion intelligence and cognitive function.
      Furthermore, these data also suggest that history of familial drug abuse may have
      a more pronounced impact on emotional and cognitive development in adolescent
      girls than boys.

PMID- 15251912
TI  - The human HPLC column: "minds-on" neuroscience for the next generation.
AB  - Science education researchers have suggested that neuroscientists can play an
      important role in science education programs for adolescents by creating "minds
      on" teaching and learning modules for scientists and teachers to use in
      classrooms. Effective educational partnerships between teachers and visiting
      scientists not only ignite student interest but also provide opportunities for
      scientist and teacher professional development. The aim of the present teaching
      module was threefold: (1) to introduce adolescents to the acute neurochemical
      effects of psychomotor stimulant drugs and their analysis using high performance
      liquid chromatography (HPLC), (2) to spur maturation of analytical reasoning
      skills among adolescents, and (3) to spark enthusiasm for science education.

PMID- 15251913
TI  - Significance of adolescent neurodevelopment for the neural circuitry of bipolar
      disorder.
AB  - The deficits of executive control of emotions and impulses of adult BD implicate
      involvement of a ventral prefrontal cortex (VPFC) neural system that subserves
      these functions that include the VPFC, as well as its subcortical connection
      sites of amygdala, striatum, and thalamus. Differences in the timing of major
      developmental changes in the structures within this neural system suggest that
      abnormalities in particular components of this neural system may emerge during
      critical developmental epochs during the course of the illness. Our recent
      neuroimaging data suggest that abnormalities in the subcortical components of
      VPFC neural systems may be evident by early adolescence in BD, whereas VPFC
      deficits progress over the course of adolescence and may be difficult to detect
      prior to late adolescence or early adulthood. This potential neurodevelopmental
      model for BD could have important implications for the recognition of early signs
      of the disorder and for age-specific treatment strategies.

PMID- 15251914
TI  - Impact of cannabis use on brain function in adolescents.
AB  - Cannabis is the most common illicit substance used by adolescents. This paper
      reports results of a pilot study using fMRI and a working memory task to compare
      brain function of adolescent cannabis users to that of two control groups, one
      matched for tobacco use and the other for nonsmokers.

PMID- 15251915
TI  - An FMRI study of response inhibition in youths with a family history of
      alcoholism.
AB  - Disinhibition among alcoholics may precede or result from alcohol use disorders
      (AUDs). It remains unclear how disinhibition might contribute to AUD risk among
      youths with a family history of alcoholism (FHP). We used functional magnetic
      resonance imaging (fMRI) to explore inhibition-related neural risk factors for
      AUD. Participants were 12- to 14-year-old nondrinkers, including 12 FHP youths
      and 14 youths with no family history of alcoholism (FHN). Youths performed a
      go/no-go task during fMRI acquisition. At a conservative threshold, FHN youths
      showed less inhibitory response than FHP youths in the left middle frontal gyrus,
      despite similar task performance between groups. Using a more liberal threshold,
      FHP youths also demonstrated less response in additional frontal regions. These
      preliminary findings suggest that FHP youths show less inhibitory frontal
      response than FHN youths. Altered neural activation among FHP youths may underlie
      subsequent disinhibition and could be related to the AUD risk.

PMID- 15251916
TI  - A comparative developmental study of impulsivity in rats and humans: the role of
      reward sensitivity.
AB  - The present study was conducted to test the hypothesis that differences in reward
      sensitivity between adolescents and adults account for differences in
      impulsivity. In a comparative study, we examined preferences for various
      concentrations of sucrose solutions as an operational measure of reward
      sensitivity in adolescent and adult rats and humans. Humans also completed self
      report measures of impulsivity and reward sensitivity. There was some indication
      that adolescents preferred sweeter solutions compared to adults. Also,
      adolescents scored substantially higher on impulsivity. However, adolescents and
      adults did not differ in self-ratings of reward sensitivity and personality
      scores were not consistently related to sucrose preferences. The data highlight
      some of the benefits and issues that arise with developing comparative measures
      in humans and animals. Future comparative research using alternative behavioral
      paradigms is necessary to determine if and how changes in reward sensitivity
      influence developmental shifts in impulsivity.

PMID- 15251917
TI  - Developmental differences in nicotine place conditioning.
AB  - To understand the motivations and implications of the prevalence of smoking,
      studies have compared the behavioral effects of nicotine, the psychoactive drug
      in tobacco, in adolescent and adult animals. The present study used a biased
      three-chambered conditioned-place preference procedure without prior habituation
      to examine the potential rewarding and anxiolytic effects of nicotine across
      adolescence and adulthood to assess the presence of age-dependent differences in
      response to nicotine.

PMID- 15251918
TI  - Age and experience affect the recruitment of new neurons to the song system of
      zebra finches during the sensitive period for song learning: ditto for vocal
      learning in humans?
AB  - Vocal learning in songbirds and humans is a complex learned skill with sensory,
      motor, and social aspects. It culminates in the imitation of sounds produced by
      other, usually older individuals. Song learning and language learning may differ
      in their cognitive content, but both require coordination of auditory feedback
      and fine motor control, which may be supported by similar brain structures. Vocal
      learning in birds as in humans requires the use of forebrain networks; in
      songbirds these networks are thought to be related, in part, to the frontal
      association cortex-basal ganglia loops that mature in humans at adolescence.

PMID- 15251919
TI  - Nicotine administration significantly alters accumbal dopamine in the adult but
      not in the adolescent rat.
AB  - Many drug-dependent adults began using drugs during adolescence. In fact,
      adolescent drug users are more likely to become drug-dependent adults than those
      abstaining from drug use until after the age of 18. Because of this, recent
      research has begun to investigate the consequences of adolescent drug use.
      Specifically, research has begun to focus on the behavioral effects of drugs on
      the developing brain and the development of drug addiction. The present study
      examined the responsiveness of the mesolimbic dopamine (DA) pathway during
      development through the use of in vivo microdialysis. Specifically, it was
      determined whether nicotine-induced accumbal DA release differs between
      adolescent and adult rats. To assess nicotine's effects across age, animals
      received acute or repeated nicotine at early adolescence (postnatal day (PND)
      35), late adolescence (PND 45), or young adulthood (PND 60). Findings suggest
      that there are significant differences between adolescent and adult animals in
      their dopaminergic response to nicotine. Adult animals had an enhanced DA
      response to acute nicotine challenge, an effect absent in adolescence.
      Additionally, this nicotine-induced increase in adults was not apparent after
      repeated nicotine treatment. These results provide insight into how the
      adolescent brain responds to nicotine and may also provide evidence as to how
      prolonged nicotine use affects normal brain development and responsiveness.

PMID- 15251920
TI  - Grid crossing: inability to compare activity levels between adolescent and adult
      rats.
AB  - Traditionally, studies measuring behavioral activity have used male adult animals
      and grid crossings (GCs) as a representative measure of activity in lieu of total
      distance moved (TDM). However, using GCs as the dependent measure may not be
      effective for comparing the activity of animals during development, as they vary
      significantly in size. The present study examines the reliability of GCs as
      opposed to TDM as an indicator of locomotor activity for comparisons during
      ontogeny using a computerized behavioral tracking system (Noldus). Rats
      (postnatal day[PND] 35, PND 60) were tracked for a period of 3 minutes inside a
      closed runway. GCs and TDM were measured for the recorded tracks. It was
      determined that GCs were positively correlated with TDM in the behavioral
      apparatus, suggesting that GCs is a reliable measure of an individual animal's
      activity. Using GCs as the dependent measure, no significant differences in
      activity were observed across age or sex. However, using TDM indicates adolescent
      rats are significantly more active than their adult counterparts. These data
      indicate that although the number of GCs is predictive of total activity, the
      slope of the relationship varies significantly with age, therefore making it
      inappropriate to use GCs when comparing across ages. Studies that use animals of
      differing age must be sensitive to baseline differences in locomotor activity.

PMID- 15251921
TI  - Developmental differences in the accumbal dopaminergic response to repeated
      ethanol exposure.
AB  - Recent research indicates that alcohol use/abuse is often initiated during the
      adolescent period and that brain reinforcement pathways (e.g., the mesolimbic
      dopamine [DA] pathway) are undergoing developmental transition. Our research
      focuses on the effects of ethanol administration on neural mechanisms associated
      with addiction in preadolescent (postnatal day [PND] 25), adolescent (PND 35, PND
      45), and young adult (PND 60) animals. Using conditioned place preference (CPP)
      testing, we have shown that adolescent animals are unique in their responses to
      ethanol. Since CPP has been associated with contextually conditioned incentive
      motivation, our results suggest that younger animals may be more vulnerable to
      addiction. The present data reveal that adolescent animals are neurochemically
      distinct in response to ethanol's effects. Using in vivo microdialysis within the
      nucleus accumbens septi (NAcc), we have determined the DAergic response across
      development. Results reveal that basal levels of DA transition during the
      adolescent period and differ from preadolescent or adult animals. Specifically,
      PND 45 animals exhibited significantly higher, and PND 25 significantly lower,
      basal DA levels than all other ages examined. Further, repeated exposure to
      ethanol elevated basal DA levels significantly regardless of age or dose. Basal
      3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio also differed as a function of
      age, with PND 35 and PND 60 animals demonstrating the highest ratios, and PND 45
      animals producing the lowest baseline levels. Repeated ethanol exposure produced
      significant changes in basal ratios as a function of age. Interestingly, PND 45
      animals exhibited no change in ratios with repeated exposure, while all other
      ages demonstrated a dose-dependent rise in DOPAC/DA ratios. These data indicate
      an age-dependent difference in the homeostatic alterations of mesolimbic systems
      in response to repeated ethanol treatment, an effect that may manifest itself as
      differences in behavioral responsivity and conditionability to the drug and the
      drug's effects.

PMID- 15251922
TI  - Age-related differences in elevated plus maze behavior between adolescent and
      adult rats.
AB  - Adolescence is a time of considerable transformations, often associated with
      increases in risk taking and novelty-seeking behaviors. Little is known of a
      possible age-dependent expression of anxiety-related behaviors in novel or
      potentially dangerous situations. The present study explored age differences in
      anxiogenic and anxiolytic stimuli between adolescent and adult Sprague-Dawley
      rats using the elevated plus maze (EPM). Data were compared across several
      experiments using factor analysis of multiple EPM measures. Under some
      circumstances, adolescents revealed a relatively low behavioral anxiety profile
      compared to adults, whereas in other situations results revealed the opposite
      pattern. Characteristics of the pretest circumstances altered considerably the
      nature of the conclusions reached regarding age-related changes in anxiogenic and
      anxiolytic stimuli. In general, anxiety measures in adolescents were less
      affected by variations in pretest conditions compared to the same variables in
      adults, suggesting possible adolescent immaturity of brain mechanisms involved in
      the regulation of anxiety.

PMID- 15251923
TI  - The cellular basis for volume changes in the rat cortex during puberty: white and
      gray matter.
AB  - We have found that developmental changes through the adolescent period in the rat
      cerebral cortex provide parallels to those seen in the human cortex. Like humans,
      the rat cerebral white matter increases during this time due to increases in the
      number of axons that become myelinated even while the total number of axons
      decreases. We have preliminary evidence that estrogen decreases the rate of
      myelination, which results in a sex difference in adult rats. Another parallel to
      the human cortex is the nonlinear changes in the size of the cortex. We have
      found that in some cortical regions, female rats show decreases in cortical
      volume and number of neurons across the time of puberty, and removal of the
      ovaries stops these decreases. The rat cortex may serve as a model for the
      cellular changes underlying the volume changes seen in adolescent humans.

PMID- 15251924
TI  - 13-cis Retinoic acid (accutane) suppresses hippocampal cell survival in mice.
AB  - Use of the acne drug Accutane (13-cis retinoic acid, [13-cis RA]) has been
      associated with severe depression. This association has been considered
      controversial because no causative link has been found between 13-cis RA and this
      disorder. A recent hypothesis has suggested that atrophy of the hippocampus can
      result in depression. We now show, in a mouse model, that endogenous RA generated
      by synthetic enzymes in the meninges acts on hippocampal granule neurons, and
      chronic (3-week) exposure to a clinical dose of 13-cis RA may result in
      hippocampal cell loss. In humans this may be conjectured to be the mechanism by
      which Accutane contributes to depression.

PMID- 15251925
TI  - The effects of ethanol on spatial and nonspatial memory in adolescent and adult
      rats studied using an appetitive paradigm.
AB  - Adolescent rats have been reported to be less sensitive than adults to many acute
      ethanol effects, including ethanol-induced sedation and motor impairment, but
      conversely more sensitive to ethanol-induced disruptions in spatial memory in a
      Morris water maze (Markwiese et al., 1998). The present study examined adolescent
      and adult rats trained for 6 days under spatial or nonspatial versions of a
      presumably less stressful sand box maze. Moderately food-deprived animals were
      given 0, 0.5, or 1.5 g/kg ethanol intraperitoneally 30 min before training each
      day, but were tested without ethanol or reinforcer on test day. Spatial
      acquisition was impaired by 1.5 g/kg in adults but not adolescents, with no
      ethanol impairment on the nonspatial task at either age. These results are
      opposite the ontogenetic profile reported by Markwiese et al., (1998) and may
      reflect differential activation of prefrontal cortex or other stress-sensitive
      forebrain regions by the two tasks across age.

PMID- 15251926
TI  - Adolescent ethanol sensitivity: hypothermia and acute tolerance.
AB  - A two-injection paradigm was used to assess acute (within-session) tolerance to
      ethanol in telemetry-implanted adolescent and adult rats. Male rats were
      intragastrically pretreated with either 1.0 g/kg of ethanol or water and then
      challenged with 2.0 g/kg of ethanol or water when blood alcohol levels (BALs) of
      ethanol-pretreated animals were anticipated to approach zero. Adults showed more
      rapid and sustained ethanol-induced hypothermia than adolescents. Acute tolerance
      to ethanol-induced hypothermia did not emerge clearly with the two-injection
      paradigm; ethanol-pretreated animals of both ages generally did not differ from
      those pretreated with water in their hypothermic response to ethanol despite
      higher BALs after the second intubation. Housing condition (paired or isolated)
      had little influence on ethanol-induced hypothermia. The adolescent attenuation
      of ethanol-induced hypothermia in this experiment was not associated with greater
      expression of within-session (acute) tolerance.

PMID- 15251927
TI  - Long-term neurobehavioral effects of alcohol or nicotine exposure in adolescent
      animal models.
AB  - Adolescent alcohol and nicotine abuse is common, but its neurodevelopmental
      consequences remain unclear. This laboratory utilized adolescent rodent models to
      assess the hypothesis that adolescents are highly susceptible to the effects of
      alcohol and nicotine. Rats were exposed to ethanol for 10-14 days using an
      intermittent vapor inhalation paradigm. Rats were continuously exposed to
      nicotine for 5 days using Nicoderm CQ transdermal patches. Alcohol or nicotine
      exposure altered neurobehavioral function when assessed after 3-7 weeks of
      abstinence. Alcohol-induced changes include increased electroencephalographic
      (EEG) frequency, decreased amplitude of the cortical N1 and hippocampal P3 event
      related potential (ERP) components, enhanced anxiety-like behavior, and enhanced
      depressive-like behavior. Nicotine-induced changes include decreased slow-wave
      cortical EEG power, increased cortical N1 ERP amplitude, decreased motor
      activity, and increased anxiety-like behavior. These findings support the
      hypothesis that adolescents are uniquely susceptible to the effects of chronic
      alcohol and nicotine exposure.

PMID- 15251928
TI  - An animal model of sensation seeking: the adolescent rat.
AB  - Previous research has established a strong relationship between a rodent's
      preference for novelty and sensitivity to psychomotor stimulants. Rats with
      greater sensitivity to the motoric effects of amphetamine exhibit higher
      preferences for novelty. Additionally, animals with high novelty preference
      scores are more easily drug conditioned and are more sensitive to, and can more
      accurately discriminate, amphetamine doses. Novelty preference in animals has
      been compared to sensation seeking in humans and is strongly correlated with drug
      use and addiction vulnerability. Thus, the present studies employed a playground
      maze procedure to measure changes in novelty preference across age following
      either four or eight habituation trials using eight distinct objects. Early-adult
      (postnatal day [PND] 59) animals did not exhibit a significant preference for a
      novel object regardless of total number of habituation trials. Early-adolescent
      animals (PND 34) exhibited a preference for the novel object in fewer than four
      habituation trials, but exhibited no preference with increased habituation
      trials. These results are counterintuitive and may demonstrate an
      overgeneralization of the habituation trials specific to adolescent animals.
      Given that adolescence is a period of heightened exploration, one would expect
      adolescent animals to demonstrate an enhanced preference for novel stimuli using
      this paradigm. However, it is possible that the complexity of the task, as
      presented, reveals differences in the establishment and behavioral manifestation
      of associations during adolescence. To address this issue, a separate novelty
      paradigm was implemented using an open-field habituation procedure followed by
      the introduction of a single novel object during the testing period. This revised
      design provides the foundation needed to better assess novelty-induced locomotor
      activity and novelty preference in adolescent rats.

PMID- 15251929
TI  - Changes in sensitivity to ethanol-induced social facilitation and social
      inhibition from early to late adolescence.
AB  - Adolescent rats are more sensitive than adults to ethanol-induced social
      facilitation, but are less sensitive to the suppression of social interactions
      seen at higher ethanol doses. Given recent findings that point to age differences
      in ethanol responsiveness, even within the adolescent period, the present study
      assessed acute effects of low to moderate doses of ethanol on social behavior of
      early, mid- or late adolescent rats. Age-related changes in responsiveness to the
      effects of ethanol on social behavior were apparent even within the adolescent
      period, with early adolescents being more sensitive to ethanol-induced social
      facilitation and less sensitive to ethanol-induced social inhibition than mid-
      and late adolescents. Given that ethanol-induced social facilitation as well as a
      lower sensitivity to the adverse effects of ethanol may contribute to heavy
      drinking, this pattern of early adolescent responsiveness to ethanol's social
      consequences may put them at higher risk for extensive alcohol use.

PMID- 15251930
TI  - Adolescent and adult rats' aversion to flavors previously paired with nicotine.
AB  - Despite the high prevalence of adolescent smoking, few studies have examined
      nicotine sensitivity during this developmental period. In the present study we
      examined adolescent and adult rats' preference/aversion for a flavor previously
      paired with nicotine. Paired (nicotine + Kool-Aid) and unpaired (Kool-Aid)
      solutions were presented in the home cage on alternating nights, with water given
      during the light phase for six days. A choice test was conducted 24 hr after the
      last night of conditioning, with both flavors presented simultaneously during the
      dark cycle. On test day, although the flavor previously paired with nicotine was
      not preferred at either age, adolescent rats consumed significantly more of the
      paired flavor than adults. These results suggest that adolescent rats are less
      sensitive to the aversive properties of nicotine. This finding taken together
      with adolescents' increased sensitivity to the rewarding properties of nicotine,
      may result in an increased vulnerability to nicotine dependence.

PMID- 15251931
TI  - The effects of methylphenidate on novel object exploration in weanling and
      periadolescent rats.
AB  - Methylphenidate (Ritalin) is used in the treatment of attention-deficit
      hyperactivity disorder. Surprisingly, little research has been conducted on the
      effects of methylphenidate during early development. Therefore, the present study
      was conducted to examine the effects of methylphenidate on object exploration in
      developing rats. Male and female weanling (21-day-old) and periadolescent (34-day
      old) Sprague-Dawley rats were tested after acute or chronic treatment with
      methylphenidate. In weanling rats, chronic methylphenidate (5.0 mg/kg) increased
      locomotor activity and disrupted novel object exploration. In periadolescent
      rats, methylphenidate disrupted exploration of the novel object, but had no
      effect on locomotor activity at any dose tested. Periadolescent rats appear to be
      less sensitive to methylphenidate-induced changes in activity compared to
      weanling animals, whereas methylphenidate disrupted novel object exploration in
      both ages. Our results suggest that methylphenidate may alter recognition memory
      and/or reactivity to or preference for novelty.

PMID- 15251932
TI  - Circulating nucleic acids and proteomics of plasma/serum: clinical utility.
AB  - Circulating tumor-specific nucleic acids have been identified in plasma, serum,
      and other body fluids from cancer patients with tumors originating in almost any
      organ site. Polymerase chain reaction provides a highly sensitive and specific
      technique for the detection of these genetic changes in a limited amount of
      tissue/fluid. The presence of elevated levels of free DNA/RNA in many medical
      conditions, malignancy, and infectious processes is being investigated for
      screening, diagnosis, prognosis, surveillance for occult disease progression,
      identifying potential therapeutic targets, and monitoring treatment response.
      Additionally, elevated fetal DNA/RNA in maternal blood is being used to determine
      gender identity, assess chromosomal abnormalities, and monitor pregnancy
      associated complications. Questions remain on the etiology, characteristics,
      stability, and potential pathologic consequences of cell-free DNA/RNA in the
      circulation. Nevertheless, nucleic acid-based assays that monitor plasma, serum,
      and body fluids provide a noninvasive, facile, and practical method for assessing
      patients. Proteomic profiling may prove complementary to a total functionality
      approach in providing a comprehensive evaluation of the patient's disease.

PMID- 15251933
TI  - Challenges for biomarkers in cancer detection.
AB  - Cancer remains the leading cause of death in the United States. Biomarkers can be
      used to detect cancer in different stages, initiation, development, and
      progression. The desirable property and utility of a biomarker lie in its ability
      to provide an early indication of disease progression. Biomarkers should be easy
      to detect, measurable across populations, and useful for detection of cancer at
      an early stage, identification of high-risk individuals, detection of recurrence,
      or monitoring endpoints in intervention studies. Recent technological advances
      have helped develop noninvasive, sensitive, and specific biomarkers to detect
      cancer at early stages of the disease.

PMID- 15251934
TI  - Quantification of circulating DNA in the plasma and serum of cancer patients.
AB  - A variety of tumor-genetic alterations have been identified circulating free-form
      in the plasma and serum of cancer patients that may have diagnostic and
      prognostic implications. Currently, no consensus exists as to whether plasma or
      serum is preferable for circulating nucleic acid analysis, and the impact of
      collection and processing on yield is unknown. We prospectively assessed DNA
      content in paired plasma and serum obtained from 10 patients with AJCC stage IV
      advanced metastatic melanoma. Blood (30 mL) was collected from each patient as
      follows: 10 mL each was processed immediately for serum and plasma and an
      additional 10 mL was incubated overnight at 37 degrees C and processed for serum.
      In addition, blood was collected from 25 normal healthy donor volunteers to
      determine the concentration of free DNA circulating in paired plasma and serum.
      DNA was isolated from 800 microl of plasma or serum and quantified. Median-free
      DNA concentrations were fourfold greater in serum than in the corresponding
      plasma sample. Serum isolated from blood allowed to clot overnight yielded four
      times more DNA than serum processed immediately. Among normal healthy volunteers,
      only serum contained detectable free DNA. These findings provide conclusive
      evidence that elevated levels of circulating DNA could be identified consistently
      in patients with cancer than in normal healthy donors. Furthermore, the method of
      blood processing may significantly affect the levels of circulating nucleic acids
      and impact the investigator's results. Significant consideration must be given to
      the methods by which circulating nucleic acids are obtained for clinical
      analysis.

PMID- 15251935
TI  - Detection and characterization of circulating microsatellite-DNA in blood of
      patients with breast cancer.
AB  - Increased levels of circulating DNA have been reported in the blood of cancer
      patients but not healthy individuals. Tumor-specific genomic aberrations, such as
      loss of heterozygosity (LOH) and microsatellite instability (MSI), can be
      detected in this free extracellular DNA. Identification of these genetic
      aberrations may play an important role in cancer diagnosis and prediction of
      disease progression. Moreover, the genomic regions involved might harbor
      potential targets for therapies. To evaluate the incidence of microsatellite
      alterations in circulating DNA, we assessed the blood serum of 34 patients with
      primary (n = 8) and metastatic (n = 24) breast cancer. Samples were also analyzed
      for the presence of circulating tumor cells using an immunocytological
      cytokeratin assay, and the concentration of the tumor marker CA 15-3 was
      determined. Genomic DNA extracted from serum and normal blood leukocytes, as a
      control, was amplified by the polymerase chain reaction using markers at 4
      microsatellite loci of chromosomes 10q22-23, 16q22-23, 17q11-12, and 17q21. In 17
      of 34 cancer patients, tumor-specific alterations were detected in serum samples.
      In 16 patients, LOH at various loci was observed, whereas MSI was only detected
      in the serum of one patient. The pattern of LOH was very heterogeneous, and LOH
      was detected at chromosomal loci 10q22-23, 16q22-23, and 17q11-12 but not 17q21.
      No correlation was found between the detection of circulating tumor DNA and the
      presence of circulating tumor cells in the blood or serum concentration of CA 15
      3. In conclusion, genomic aberrations on chromosomes 10, 16, and 17 are frequent
      in the circulating DNA of breast cancer patients. However, circulating tumor DNA
      does not reflect the presence of tumor cells in blood or the level of tumor
      associated protein markers such as CA 15-3. Thus, screening for circulating tumor
      DNA may provide additional diagnostic information.

PMID- 15251936
TI  - Circulating methylated DNA.
AB  - Early detection of cancer would facilitate better management of patients, because
      survival is greatly affected by stage of presentation. Circulating nucleic acids
      represent a biomarker that might be used in the early detection of cancer. In
      addition, such biomarkers could potentially be used to follow the progression of
      patients with cancer. DNA methylation of the promoter region CpG islands of genes
      represents one such nucleic acid-based marker, and possesses some advantages over
      other approaches. These include the stability of DNA as a molecule, the ability
      to detect such changes using simple polymerase chain reaction-based approaches,
      and the potential for methylated DNA to be preferentially present in nucleosomes
      in plasma or serum. These factors are presented and their impact on the detection
      of methylated DNA circulating in the bloodstream is demonstrated.

PMID- 15251937
TI  - Detection of promoter hypermethylation of tumor suppressor genes in urine from
      kidney cancer patients.
AB  - Kidney cancer is curable by surgical resection and therapy, if detected at an
      early stage. Using sensitive methylation-specific polymerase chain reaction, we
      screened matched tumor DNA and preoperative urine DNA from 50 kidney cancer
      patients, for hypermethylation of a panel of six normally unmethylated tumor
      suppressor genes: VHL, p16/CDKN2a, p14ARF, APC, RASSF1A, and Timp-3. When
      compared to the tumor DNA, an identical pattern of gene hypermethylation was
      found in the matched urine DNA from 44 of 50 patients (88% sensitivity) including
      27 of 30 cases of stage I disease. By contrast, hypermethylation was not observed
      in normal and benign disease controls (100% specificity). We conclude that
      promoter hypermethylation is a common and early event in kidney tumorigenesis and
      can be detected in the urine DNA from patients with organ-confined renal cancer
      of all histologic types.

PMID- 15251938
TI  - Prognostic DNA methylation marker in serum of cancer patients.
AB  - Changes in the status of DNA methylation are among the most common molecular
      alterations in human neoplasia. Recent demonstrations of tumor-derived methylated
      DNA in the blood stream of cancer patients allow the use of these epigenetic
      markers for risk assessment in cancer patients. We were interested in evaluating
      the prognostic value of several methylated genes in the serum of cancer patients.
      Using MethyLight, a high-throughput DNA methylation assay, we analyzed 215 serum
      samples from patients with cervical (n = 93) or breast cancer (n = 122) for DNA
      methylation changes. In cervical cancer, hypermethylation of three genes (MYOD1,
      CDH1, and CDH13) in pretreatment sera was statistically significantly associated
      with a poorer disease outcome. Additionally, for the first time we used a so
      called gene evaluation set to identify the most important DNA methylation changes
      in the serum of breast cancer patients from a long list of candidate genes. In
      the gene evaluation set, we detected five genes (ESR1, APC, HSD17B4, HIC1, and
      RASSF1A) using our criteria for further analysis. Finally, two of the evaluated
      genes (APC and RASSF1A) proved to be independent prognostic parameters in breast
      cancer patients. In summary, we detected several prognostic DNA methylation
      markers in the serum of cervical and breast cancer patients. This finding
      indicates great potential for the use of these epigenetic markers in clinical,
      routine risk assessment in patients with various malignancies.

PMID- 15251939
TI  - Detection of mitochondrial DNA alterations in plasma of malignant melanoma
      patients.
AB  - Genetic changes in mitochondrial DNA (mtDNA) have been detected in a variety of
      pathologic conditions including cancer. We hypothesized that malignant melanoma
      has genetic alterations in the displacement loop (D-loop) region and that these
      mtDNA alterations can be detected in blood as a circulating DNA melanoma marker.
      D-loop region from 20 melanoma cell lines, 12 metastatic melanoma specimens, and
      corresponding lymphocytes and plasma samples were sequenced using the CEQ 8000 XL
      Genetic Analysis System (Beckman Coulter). Nine of 20 (45%) melanoma cell lines
      and 5 of 12 (42%) melanoma specimens contained somatic mutations in the D-loop
      region of mtDNA. DNA alterations in the polycytosine tract (C-tract) of D-loop
      were detected in 6 of 20 (30%) cell lines and 2 of 12 (17%) specimens. Two of
      five paired plasma samples (40%) contained the same mutations as did melanoma
      specimens. In a comparison of lymphocytes and plasma of melanoma patients, 9 of
      44 paired plasma samples (20%) contained at least one mutation compared to
      corresponding lymphocytes. Somatic mutations in the D-loop region of tumor and
      paired plasma did not correlate with the clinicopathological characteristics.
      However, circulating mtDNA alterations were more frequent in advanced disease.
      Studies indicate that circulating mtDNA mutations in the plasma of melanoma
      patients can be detected.

PMID- 15251940
TI  - Mutant DNA in plasma of lung cancer patients: potential for monitoring response
      to therapy.
AB  - The hypothesis tested was that mutant tumor DNA shed into plasma would show
      predictive value for monitoring response to therapy in non-small cell lung
      carcinoma patients. Pretreatment plasma specimens from 25 patients on a phase I
      trial were evaluated, 12 with paired posttreatment specimens, and 138 patients on
      the Southwest Oncology Group S0003 trial, 38 with paired posttreatment specimens,
      for the presence of K-RAS mutations. Thirteen tumor specimens from the phase I
      trial patients and seven tumor specimens from S0003 patients were also available
      for comparative analysis of K-RAS mutations in tumor tissue and plasma. All
      patients were treated similarly with paclitaxel, and carboplatin chemotherapy.
      DNA was extracted and mutational analyses performed using an RFLP-PCR assay. K
      RAS mutations were found in plasma DNA in 5/25 of the phase I patients (20%).
      Median survival was 10 months in all patients, 11.4 months in the wild-type K-RAS
      group, and 3.3 months in the mutant K-RAS group (P = 0.056). Point mutations in
      plasma DNA were identical to mutations found in the tumors, confirming the tumor
      as the source. In two patients with K-RAS mutations pretreatment, posttreatment
      plasmas were evaluated: a patient with clinical progressive disease retained the
      mutant DNA, while in a patient with a complete response (CR), the K-RAS mutation
      was no longer detectable. In an ongoing analysis of S0003 patients, to date, K
      RAS mutations have been found in the plasma of 14 patients (10.1%). In 42 matched
      pre- and posttreatment specimens from both phase I and S0003 trials, four
      patients had K-RAS mutations pretreatment that were not detectable posttreatment.
      Of these, two had a clinical CR or partial response, and the other two had stable
      disease. It was concluded that detection of tumor DNA in plasma is feasible using
      molecular techniques and that this approach shows promise for monitoring patient
      response to therapy.

PMID- 15251941
TI  - TP53 gene in blood plasma DNA of tumor patients.
AB  - Tumor-specific TP53 mutations are detectable in the blood plasma of tumor
      patients. Mutations of the TP53 tumor suppressor gene are risk factors for tumor
      progression. The objective of this work is to compare the presence of TP53
      mutations in plasma-DNA before and after tumor treatment with the status of this
      gene in the tumor tissue sample. DNA was extracted from plasma samples of 25
      patients with gastrointestinal tumors, and from paraffin-embedded tumor tissues
      from the same patients. Temperature gradient gel electrophoresis (TGGE) was
      performed for mutation screening of exons 5-8 of GC-clamped polymerase chain
      reaction products. Mutation-positive and wildtype gel bands from TGGE were cut
      and reamplified for fluorescence-labeled sequence analysis. The results of
      several mutation analyses were correlated with analysis of p53 autoantibodies in
      the same plasma. Mutation frequency (one or several mutations per sample) was
      7.1% in blood plasma of tumor-free patients, 87.0% in tumor tissues, 78.6% in
      plasma before tumor treatment, and 36.8% after treatment. Fifteen of 22 mutations
      in tumor tissues of 13 patients also were detected in the same exons of plasma
      before treatment (68.2%). Mutations in plasma after treatment (2-684 days) were
      the same in 6 of 30 cases of tissue mutations only. Six of seven patients with
      mutations after treatment in their plasma had metastases. One patient was p53
      autoantibody negative, but has a terminator mutation of codon 196 in tissue and
      in posttreatment plasma as well. Genetic analysis of plasma in tumor patients
      should be further developed, as it might be of prognostic value.

PMID- 15251942
TI  - Molecular serological diagnosis in transitional cell bladder cancer.
AB  - There are no reliable serological tumor markers for transitional cell carcinoma
      (TCC) of the urinary bladder. Fluorescent microsatellite analysis (MSA) was used
      to detect serum-DNA alterations in patients with bladder cancer. Prospectively,
      fresh tumor-, peripheral blood-, and serum-specimens were collected from 58
      consecutive patients treated for TCC of the bladder to obtain the corresponding
      DNA. DNA was extracted by the phenol-chloroform method from tumors and blood
      lymphocytes. Serum DNA was isolated by a commercial kit. Fluorescent MSA was
      performed with a total of 17 polymorphic markers from chromosomal regions 5q, 8p,
      9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 58 cancer specimens as well as in
      specimens from 20 healthy controls. Detection of allelic imbalance and loss of
      heterozygosity in the tumor and serum specimens was carried out on an automated
      laser sequencer. Serum-DNA alterations were identified in 79.3% (46/58). Four
      healthy controls displayed serum-DNA artefacts rendering a specificity of 80%.
      The highest frequency of serum-DNA alterations (38%) was detected for chromosomal
      region 8p. Chromosomes 5q, 9p, and 20q showed serum-DNA alterations in 20% to
      23%. Identification of tumor-specific serum-DNA alterations was stage independent
      (P >0.05), but was more frequent in high-grade tumors (P = 0.08). To optimize
      specificity, simultaneous analysis of tumor DNA is advised to rule out artefacts
      resembling allelic imbalance in MSA of serum DNA. The method then has potential
      for application as a "serological marker" in the follow-up of patients after
      radical surgical therapy for invasive TCC of the bladder.

PMID- 15251943
TI  - Role of cell-free plasma DNA as a diagnostic marker for prostate cancer.
AB  - Recent evidence has shown elevated levels of cell-free plasma DNA in cancer
      patients. The aim of the present study was to quantify and compare the levels of
      cell-free plasma DNA in patients with prostate cancer, prostatic intraepithelial
      neoplasia (PIN), and benign prostatic hypertrophy (BPH) to examine if it offered
      a useful diagnostic test. Blood samples were obtained from 37 patients attending
      a clinic for prostate biopsies. Samples were taken prior to biopsy, within 1 hour
      of the biopsy, and then 2 weeks later. DNA was extracted using a QIAamp blood kit
      (Qiagen) and plasma DNA measured, in genome equivalents/milliliter plasma
      (GE/mL), using real-time quantitative PCR for the beta-globin gene. Prior to
      biopsy, plasma DNA concentration in BPH patients was 936 GE/mL (median; range:
      633-2074 GE/mL), while cancer and PIN patients had significantly higher levels of
      DNA at 1734 GE/mL (median; range: 351-3131 GE/mL; P = 0.01) and 1780 GE/mL
      (median; range: 1514-2732 GE/mL; P = 0.04), respectively. Comparison of plasma
      DNA concentration before and after biopsy showed that 60 minutes after biopsy
      values were significantly higher in both BPH (1494 GE/mL; range: 613-2522 GE/mL;
      P = 0.029) and cancer (2758; range: 1498-5226 GE/mL; P = 0.007) patients. ROC
      analysis of the data indicated a sensitivity of 85% and a specificity of 73% when
      DNA concentration of 1000 GE/mL was taken as an indicator of malignancy or PIN.
      The data suggest that quantification of cell-free plasma DNA may have an
      important diagnostic role in distinguishing benign and malignant prostate
      disease.

PMID- 15251944
TI  - Transrenal DNA as a diagnostic tool: important technical notes.
AB  - A small portion of DNA from apoptotic cells escapes complete degradation, appears
      in blood as oligonucleosomal-size fragments, is excreted in the urine, and can be
      used for diagnostic purposes. More detailed study revealed that transrenal DNA
      (Tr-DNA) belongs to a relatively low molecular-weight (150-250 bp) fraction,
      thereby requiring more careful attention to methods employed for purification and
      analysis. For example, here it is demonstrated that the QIAamp blood kit purifies
      primarily high molecular-weight DNA from serum, whereas the Guanidine/Promega
      Wizard Resin (GITC/WR) method purifies primarily low molecular-weight DNA. As a
      result, sensitivity in detection of K-RAS mutations in serum of patients with
      colorectal tumors is significantly higher with DNA isolated with the GITC/WR
      method than with the QIAamp kit. Amplicon size is also extremely important in
      analysis of Tr-DNA, because the shorter the amplicon, the higher is the
      sensitivity of biomarker detection in Tr-DNA. One hundred fifty-seven and 87 bp
      amplicons were employed for detection of mutant K-RAS in DNA isolated from 0.1 mL
      of urine obtained from 15 patients with pancreatic cancer. Mutant K-RAS was found
      in Tr-DNA of 3 and 10 patients with the long and short amplicons, respectively.
      The sensitivity and specificity of detection of mutant sequences are reduced in
      the presence of high excess of a respective wild-type allele, but they can be
      significantly increased through application of enriched polymerase chain reaction
      (PCR), peptide nucleic acid (PNA) clamped PCR, and/or stencil-aided mutation
      analysis (SAMA), based on selective pre-PCR elimination of wild-type sequences.

PMID- 15251945
TI  - Fetal cell-free nucleic acids in the maternal circulation: new clinical
      applications.
AB  - Six years after the demonstration of the presence of cell-free fetal nucleic
      acids in maternal plasma, perinatal clinical applications continue to expand. The
      focus of this article is on advances that have occurred since the CNAPS II
      conference held in Hong Kong in 2001. Circulating fetal DNA levels (fDNA) are
      elevated in pregnancies complicated by fetal trisomies 13 and 21 but not 18.
      Measurement of fDNA levels improves the performance of the current standard
      maternal serum screen, by increasing the detection of Down syndrome cases by 5%
      with no increase in the false-positive rate. fDNA levels are elevated in women
      who have developed clinical symptoms of preeclampsia, but they are also elevated
      by the early second trimester in women who will eventually develop preeclampsia.
      fDNA and mRNA gamma globin measurement may have clinical utility as markers for
      fetomaternal hemorrhage in the late first trimester. Cell-free fetal DNA levels
      are quite high in the amniotic fluid, permitting fetal genomic isolation and
      analysis using comparative genomic hybridization techniques. Fetal DNA crosses
      the blood-brain barrier and is detectable in maternal cerebrospinal fluid in a
      subset of pregnant women. The biological implications of this are currently
      unknown. Review of the literature suggests that the placenta is the predominant
      source of the circulating fetal nucleic acids. However, detection of gamma globin
      mRNA sequences in the plasma of pregnant women suggests that fetal blood cells
      also contribute to the pool of nucleic acids. Widespread incorporation of fetal
      nucleic acid measurement into routine prenatal care depends on the identification
      of a readily accessible gender-independent fetal marker.

PMID- 15251946
TI  - Recent developments in fetal DNA in maternal plasma.
AB  - It has been several years since the presence of fetal DNA in maternal plasma was
      first discovered. Numerous potential applications have been reported to date.
      However, the study of maternal plasma for the prenatal diagnosis of fetal genetic
      traits has largely centered on paternally inherited autosomal dominant traits.
      Recently, a number of approaches have been developed that allow the prenatal
      assessment of autosomal recessive conditions through fetal DNA analysis in
      maternal plasma. On the other hand, aberrations in fetal DNA concentrations in
      maternal plasma have been reported in a number of pregnancy-associated
      conditions. Recent studies have begun to address the possible underlying
      mechanisms causing such quantitative aberrations. Current studies on circulating
      fetal DNA have focused on the detection of the paternally inherited fetal
      specific alleles in maternal plasma. However, it has been demonstrated that the
      development of fetal epigenetic markers has great potential to expand the field.

PMID- 15251947
TI  - Feasibility study for a microchip-based approach for noninvasive prenatal
      diagnosis of genetic diseases.
AB  - Fetal DNA in maternal plasma may represent a source of genetic material for
      prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of
      physiological pregnancies to determine if fetal DNA can be retrieved at any
      gestational week in sufficient quantity to be analyzed with advanced mutation
      detection technologies. We performed fetal DNA quantification by real-time
      polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40
      gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were
      correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no
      amplification was obtained. For noninvasive testing, complete clearance of fetal
      DNA after delivery is mandatory. Long-term persistence was not detected in women
      with previous sons or abortions. These findings confirm that maternal plasma may
      represent the optimal source of fetal genetic material. For noninvasive diagnosis
      of genetic diseases, we evaluated microchip technology. The detection limit for a
      minority allele determined by diluting a mutated DNA into a wild-type plasma
      sample was 5 genome equivalents, indicating that the test might be applied to the
      identification of paternally inherited fetal alleles in maternal plasma. The
      addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip
      hybridization mixture allowed approximately 50% inhibition of wild-type allele
      signals.

PMID- 15251948
TI  - Rapid clearance of fetal cells from maternal circulation after delivery.
AB  - We previously reported increased apoptosis in the maternal circulation during
      pregnancy, partly accounting for the presence of cell-free fetal DNA in maternal
      plasma. In the current study, apoptosis was quantitated in 60 peripheral blood
      samples obtained from 15 women sequentially tested postpartum using the binding
      of annexin V. FISH with X/Y probes was performed on annexin V-positive cells
      isolated by MACS in patients with male fetuses to estimate the proportion of
      fetal cells among the apoptotic cell population. Twenty-four women at the thirty
      seventh to thirty-eighth week of gestation and 35 nonpregnant females were used
      as controls. Apoptosis rate in the thirty-seventh to thirty-eighth week was 12.5%
      (9.2-14.7%). At 30 minutes, 12 hours, 24 hours, and 48 hours postpartum, it was
      25.1% (16.8-28.5%), 12.5% (10.9-14.1%), 6.1% (4.8-7.1%), and 2.3% (1.3-3.0%),
      respectively. Male apoptotic cells were identified in all cases with male fetuses
      at 37 to 38 weeks of gestation, and the mean proportion was 9.9% (5.9-13.2%). The
      proportion of fetal cells 30 minutes after delivery was 14.8% (12.5-25.5%) and 12
      hours postpartum 2.1% (0.8-4.1%). Male fetal apoptotic cells were detected in
      three of eight samples collected 24 hours after delivery from women who delivered
      males, at frequencies of 0.10%, 0.15%, and 0.25% (mean 0.16%). There were no
      fetal apoptotic cells 48 hours after delivery. Apoptosis partly accounts for the
      clearance of fetal cells from the maternal circulation. Because it is a rapid
      reaction, completed within 2-3 hours, persistence of fetal cells is possibly due
      to apoptosis-resistant progenitors or to defective regulation of apoptosis,
      leading to fetal cell microchimerism associated with autoimmune diseases.

PMID- 15251949
TI  - A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using
      free fetal DNA in maternal plasma.
AB  - Antenatal determination of fetal blood group is important in pregnancies with a
      significant risk of hemolytic anemia due to maternal alloimmunization. The
      International Blood Group Reference Laboratory (part of the National Blood
      Service) in Bristol, UK, provides a fetal blood group genotyping service to
      obstetricians caring for immunized pregnant women with heterozygous partners.
      Since 2001, fetal D typing has been offered using free fetal DNA in maternal
      plasma. Real-time polymerase chain reaction (PCR) assays are performed to detect
      the RHD gene. To confirm the presence of fetal DNA when RHD is not detected, Y
      chromosome sequences are targeted. When a D-negative female fetus is predicted,
      maternal buffy coat DNA is tested for eight insertion/deletion polymorphisms.
      Sequences that are absent from the maternal genome are then targeted in maternal
      plasma and are used to confirm the presence of free fetal DNA in the blood
      sample. Currently, 283 pregnancies have been tested, of which 50 are awaiting
      confirmatory results. Fetal D status was correctly predicted in 223 cases, and no
      result was obtainable in 7 cases. In three cases, serology on cord blood was
      discrepant with reported results, but all fetuses had received multiple
      intrauterine transfusions. The new test has significantly reduced the number of
      invasive procedures carried out in the UK for fetal D grouping. Antenatal anti-D
      prophylaxis is currently being introduced in the UK to all D-negative women; in
      the future, detection of fetal RHD sequences in maternal plasma may allow anti-D
      to be restricted to pregnancies involving a D-positive fetus.

PMID- 15251950
TI  - Can circulatory fetal DNA be used to study placentation at high altitude?
AB  - Pregnancy at high altitude (>2700 m) is associated with higher rates of fetal
      growth restriction and preeclampsia as well as alterations in placentation,
      including increased villous vascularization and reduced remodeling of maternal
      spiral arteries. Because circulatory fetal DNA concentrations were shown to be
      enhanced in pregnancies affected by preeclampsia, we investigated whether similar
      elevations are also apparent in pregnancies at high altitude by examining ethnic
      Tibetans and recent migrant Han Chinese residents in Lhasa (altitude 3650 m) as
      well as Han Chinese residents in Guangzhou (altitude 7 m). Our data from this
      preliminary study (n = 10/study group) indicate that circulatory fetal DNA levels
      were significantly higher in the unremarkable pregnancies of Han women who moved
      to Tibet when compared to Han women at sea level. No significant difference could
      be discerned between migrant Han Chinese and ethnic Tibetans living in Lhasa. Our
      data, therefore, suggest that pregnancy at high altitude is associated with an
      increased liberation of cell-free fetal DNA and that no major ethnic differences
      are apparent.

PMID- 15251951
TI  - Circulating cell-free fetal nucleic acid analysis may be a novel marker of
      fetomaternal hemorrhage after elective first-trimester termination of pregnancy.
AB  - Analysis of cell-free fetal DNA (fDNA) and RNA in maternal plasma could be useful
      in the diagnosis and management of complications of pregnancy. In this review, we
      discuss our studies to investigate the potential of fetal nucleic acid
      measurement in maternal plasma as a marker of fetomaternal hemorrhage (FMH) after
      elective first-trimester termination of pregnancy (TOP). Using quantitative real
      time PCR amplification of the DYS1 sequence, elevation of plasma fDNA levels
      after TOP was observed, especially in the late first trimester. This corresponds
      with the functional development of the placental vascular structure and fetal
      hematopoiesis. This Y sequence-based PCR amplification assay, however, limits the
      analysis to pregnant women carrying male fetuses. Therefore, we also developed a
      real-time quantitative reverse-transcriptase PCR assay of the gamma-globin
      transcript as a marker of fetal erythroid cells. Although plasma gamma-globin
      mRNA levels were decreased after TOP in many patients, an elevation was observed
      in some patients at greater than 9 weeks' gestation, which is consistent with the
      increase in plasma fDNA levels. Our data suggest that fetal hematopoietic cells
      contribute to the pool of fetal nucleic acids in the maternal circulation.
      Measurement of cell-free fetal nucleic acid levels in maternal plasma may have
      clinical application as a novel marker of FMH after 9 weeks of gestation.

PMID- 15251952
TI  - The biology and diagnostic applications of plasma RNA.
AB  - The detection of cell-free RNA in the plasma and serum of human subjects has
      opened up new investigational opportunities. Tumor-derived RNA was detected in
      the plasma and serum of patients with various forms of cancer. Through the
      development of robust extraction and quantification protocols for circulating
      RNA, new information regarding its biology and characteristics has been obtained.
      Plasma RNA was shown to be particle associated and to be surprisingly stable.
      Recently, fetal RNA was also demonstrated in maternal plasma. The placenta was
      shown to be an important source of such circulating fetal RNA. This discovery has
      created new prenatal diagnostic and monitoring possibilities. It is expected that
      circulating RNA will find application in many other clinical scenarios, including
      emergency medicine.

PMID- 15251953
TI  - Detection of tumor-specific mRNA in cell-free bronchial lavage supernatant in
      patients with lung cancer.
AB  - Bronchoscopy is a standard procedure in the workup of patients with suspicious
      pulmonary lesions. We wondered whether it is possible to isolate malignancy
      associated mRNA from cell-free lavage supernatant. Extracellular mRNA from cell
      free lavage supernatant of 25 patients with lung cancer (23 with non-small cell
      lung cancer, 2 with small cell lung cancer) was isolated, reverse-transcribed,
      and amplified by reverse transcriptase polymerase chain reaction. The quantity
      and quality of the isolated RNA were checked after cDNA synthesis by
      amplification with beta-actin-specific primers. Afterwards, a panel of eight
      genes known to be expressed in lung tumors was used for the detection of tumor
      associated mRNA expression in lavage supernatant and serum. mRNA coding for beta
      actin could be isolated from lavage supernatant of all 25 patients. In addition,
      the expression of at least one tumor-associated gene was detectable in all
      patients. These results show that intact mRNA can be isolated from cell-free
      lavage supernatant and that its quantity and quality are sufficient for the
      detection of tumor-associated gene expression alterations. This may open new
      possibilities for the diagnosis of lung cancer.

PMID- 15251954
TI  - Real-time quantitative PCR measurement of thyroglobulin mRNA in peripheral blood
      of thyroid cancer patients and healthy subjects.
AB  - Follow-up of recurrent differentiated thyroid carcinoma involves the measurement
      of serum thyroglobulin (Tg). However, Tg autoantibodies are present in a high
      proportion of thyroid carcinoma patients (up to 25%) and these can interfere with
      the Tg immunoassays. To overcome this obstacle, investigators have used real-time
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to measure
      Tg mRNA in the blood of patients with differentiated thyroid cancer, with varying
      degrees of success. In the present study, we demonstrate the first reported use
      of the PAXgene Blood RNA collection tube and extraction kit method for the
      preparation of RT-PCR-quality RNA with subsequent deployment of the latter in the
      development of a specific, sensitive, and reproducible Taqman assay for the
      detection and quantification of thyroglobulin mRNA. Beta-actin mRNA was also
      assayed and results are expressed as a ratio of Tg to beta-actin mRNA. The intra
      assay coefficient of variations (CVs) for Tg and beta-actin mRNA assay were 27.7%
      and 25.4%, respectively. Inter-assay CVs were 20.8% and 28.8%, respectively, for
      the two assays. Tg mRNA was detected in all cancer subjects (n = 42) and healthy
      individuals (n = 20). Tg mRNA was significantly higher in cancer patients than in
      the healthy subjects (0.00169 +/- 0.00013 vs. 0.00051 +/- 0.00015; P<0.0001).
      Fourteen cancer patients had detectable levels of serum Tg, and Tg mRNA levels
      tended to be higher in these than in cancer subjects with undetectable serum Tg
      (0.00188 +/- 0.00021 vs. 0.00157 +/- 0.000178; P = 0.08). Circulatory Tg mRNA
      measurement may serve a useful role in the assessment of thyroid cancer.

PMID- 15251955
TI  - Real-time quantitative PCR measurement of circulatory rhodopsin mRNA in healthy
      subjects and patients with diabetic retinopathy.
AB  - Diabetic retinopathy is the commonest complication of diabetes and is the biggest
      single cause of registered blindness in the UK. No biochemical tests exist to
      determine the precise state and rate of change of the eyes in the diabetic
      patient. In the present study, using real-time quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR), we measured mRNA encoding the retina-specific
      pigment protein rhodopsin (RHO) in the peripheral blood of healthy individuals (n
      = 20) and diabetic patients (n = 46) with and without retinopathy. Beta-actin
      mRNA was also assayed and results are expressed as a ratio of RHO to beta-actin
      mRNA. Peripheral blood was taken by venipucture directly into PAXgene Blood RNA
      collection tubes and RNA extracted by use of the PAXgene Blood RNA extraction
      kit, as per the manufacturer's (Qiagen) instructions. Diabetic patients were
      divided into three groups defined by the severity of retinopathy as assessed by
      fundoscopy: A, diabetic without retinopathy; B, background retinopathy; and C,
      preproliferative retinopathy. Medians of the ratios between groups were compared.
      RHO mRNA was successfully detected and quantified in peripheral blood in all
      healthy and diabetic groups, with levels shown to be significantly higher in
      diabetic patients than in healthy controls (2.54 x 10(-5) vs. 1.29 x 10(-5); P =
      0.002). Significant differences in RHO mRNA levels were also seen between healthy
      control subjects and diabetic groups A (2.52 x 10(-5); P = 0.022), B (1.98 x 10(
      5); P = 0.028), and C (5.08 x 10(-5); P = 0.002). The results suggest that there
      is an increase in circulatory RHO mRNA with the severity of diabetic retinopathy.

PMID- 15251956
TI  - The use of real-time quantitative PCR to detect circulating prostate-specific
      membrane antigen mRNA in patients with prostate carcinoma.
AB  - Prostate-specific antigen (PSA) has long been criticized for its lack of
      specificity in screening for the occurrence of prostate cancer. In this study, we
      tried to measure levels of another biomarker, prostate-specific membrane antigen
      (PSM), in the peripheral circulation from subjects with either prostate cancer or
      benign prostatic hyperplasia (BPH). Total RNA was extracted from blood samples of
      70 patients with prostate cancer and 19 with BPH. Reverse transcription was
      performed to convert mRNA to cDNA. The cDNA was analyzed with a novel real-time
      quantitative polymerase chain reaction (PCR) protocol to measure PSM mRNA levels
      in the circulation. Melting curve analysis was adapted to assure that correct
      amplification data were obtained. Results showed that 41 of 70 prostate cancer
      patients had positive results, whereas 9 of 19 BPH cases were negative.
      Therefore, the sensitivity and specificity were determined to be 58.6% and 47.4%,
      respectively. For comparison, traditional nested PCR was performed to investigate
      whether the new method was superior. The sensitivity and specificity of nested
      PCR were determined to be 27.1% and 57.9%, respectively. The detection limits of
      these two methods were 0.0005 ng (for the real-time quantitative PCR method) and
      0.5 ng of PSM-cDNA (for the nested PCR method). In conclusion, we have
      successfully developed a novel, noninvasive real-time quantitative PCR method to
      detect the PSM mRNA levels in the peripheral circulation of prostate cancer
      subjects. This method may provide references for urologists diagnosing prostate
      cancer or monitoring the patient's condition after treatment.

PMID- 15251957
TI  - Extracellular and circulating redox- and metalloregulated eRNA and eRNP: copper
      ion-structured RNA cytokines (angiotropin ribokines) and bioaptamer targets
      imparting RNA chaperone and novel biofunctions to S100-EF-hand and disease
      associated proteins.
AB  - Bioassays for cellular differentiation and tissue morphogenesis were used to
      design methods for isolation of bioactive redox- and metalloregulated nucleic
      acids and copper ion complexes with proteins from extracellular, circulating,
      wound, and supernatant fluids of cultured cells. In extracellular biospheres,
      diversities of nucleic acids were found to be secreted by cells upon activation.
      They may reflect nucleic acid biolibraries with molecular imprints of cellular
      history. After removal of protein components, eRNA prototypes exuded by activated
      cells were sequenced. They are small, endogenous, highly modified and edited,
      redox- and metalloregulated 5'-end phosphorylated extracellular eRNA
      (approximately 2-200 bases) with cellular, enzymic, and bioaptamer functions.
      Fenton-type OH* radical redox reactions may form modified nucleotides in RNA as
      wobbles eRNA per se, or as copper ion-complex with protein (e.g., S100A12-EF-hand
      protein, angiotropin-related protein, calgranulin-C, hippocampal neurite
      differentiation factor) are shown to be bioactive in vivo and in vitro as
      cytokines (ribokines) and as nonmitogenic angiomorphogens for endothelial cell
      differentiation in the formation of organoid supracellular capillary structures.
      As bioaptamers, copper ion-structured eRNA imparts novel biofunctions to proteins
      that they do not have on their own. The origin of extracellular RNA and
      intermediate precursors (up to 500 bases) was traced to intracellular parent
      nucleic acids. Intermediate precursors with and without partial homology were
      found. This suggests that bioaptamers are not directly retranslatable gene
      products. Metalloregulated eRNA bioaptamer function was investigated by domains
      (e.g. 5'...CUG...3' hairpin loop) for folding, bioactivity, and binding of
      protein with copper, calcium, and alkali metal ion affinity. Vice versa,
      metalloregulated nucleic acid-binding domains (K3H, R3H) in proteins were
      identified. Interaction of protein and eRNA docking potentials were visualized by
      3D-rapid prototyping of accurate molecular image models based on crystallographic
      or NMR data. For S100A12-homologous proteins, receptor- and metalloregulated RNA
      chaperone-shaped protein assemblies were investigated. They suggest insight into
      signaling cascades as to how eRNA transmits its cytokine (ribokine)
      bioinformation from the extracellular RNA biosphere into cells. Proteomics of the
      extracellular RNA biosphere demonstrate the presence of nucleic acid-binding
      domain homologies in defense-, aging-, and disease-associated neuronal and other
      proteins as targets for RNA orphans. By structural relationships found to
      transmissible processes, proteinaceous transfer ("infectivity") and feedback of
      bioinformation beyond the central dogma of molecular biology are considered in
      terms of metalloregulated RNA bioaptamer function, nucleic acid-binding domains,
      and protein conformation.

PMID- 15251958
TI  - Improved conditions for isolation and quantification of RNA in urine specimens.
AB  - There is clear evidence that the occurrence of specific mRNAs in plasma and serum
      is associated with cancer, while the usefulness of other body fluids for nucleic
      acid-based cancer detection remains to be elucidated. Nevertheless, due to the
      principal advantages of urine (large sample quantities, easy to acquire), several
      attempts were made to use quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR)-based detection of putative RNA tumor markers from urine as a
      tool for noninvasive tumor detection. Because most of the commercially available
      RNA isolation systems do not accommodate larger sample volumes, the majority of
      experiments were performed using urine pellets. During the centrifugation step,
      putative extracellular nucleic acids of low molecular weight as well as complexes
      containing nucleic acids with low density are lost. Furthermore, cells may be
      destroyed during this procedure, and the subsequently released nucleic acids will
      quickly be degraded by nucleases in the urine, which may give rise to
      inconsistent results. Therefore, we established an improved protocol for the
      isolation of RNA from urine and subsequent quantification steps. The isolation
      procedure was tested using a quantitative RT-PCR specific for Ki-67 RNA as well
      as a radioactive-based reverse transcription approach.

PMID- 15251959
TI  - Extracellular ribonucleic acids of human milk.
AB  - Human milk has been shown to contain heterogeneous oligoribonucleotides varying
      in size from dimers to 100 mers. The sets of long oligonucleotides in milk
      samples from different donors and from different stages of lactation have some
      conservative elements. Sequences of some RNA oligonucleotides correspond to the
      3'-part of 5.8S human ribosomal RNA and to 3'-parts of tRNAVal and tRNATyr.
      Primary structures of other oligo-RNAs are homologous to fragments of human 18S
      and 28S rRNAs. Concentration of RNA in milk samples tends to decrease with
      lactation development. The change of RNA concentration and the low concentration
      of DNA in milk plasma suggest that the source of RNA in human milk may be active
      secretion of RNA by mammary gland cells.

PMID- 15251960
TI  - Transcession of DNA from bacteria to human cells in culture: a possible role in
      oncogenesis.
AB  - The human organism is continuously in close contact with microorganisms,
      especially bacteria. In the present work, by means of a real-time polymerase
      chain reaction (PCR) technique, we looked for the presence of a distinct
      bacterial gene in human cells. To this end, we cultured a human cell line, HL60,
      in a supernatant in which bacteria (Bacillus subtilis) had been grown. A
      transient transcession of bacterial DNA into the human cells was observed.

PMID- 15251961
TI  - Detection of cell-free DNA in bronchial lavage fluid supernatants of patients
      with lung cancer.
AB  - Recently, it was shown that it is possible to isolate free circulating DNA from
      plasma/serum of patients with benign and malignant diseases. In addition, several
      groups were able to detect tumor-associated alterations in these nucleic acids.
      We wondered whether any nucleic acids are detectable in cell-free bronchial
      lavage supernatants, which until now have been discarded after cell harvest.
      Additionally, we wanted to find out if it is possible to detect tumor-associated
      alterations in these DNA molecules. DNA was isolated from cell-free lavage
      supernatants from 30 lung cancer patients, and the DNA was examined for
      microsatellite alterations. Intact DNA could be isolated from all cell-free
      bronchial lavage supernatants. Microsatellite alterations were found in lavage
      supernatants of 12 of 30 patients and in lavage cells of 6 of 30 patients.
      Altogether, alterations were found in 14 of 30 patients. Thus, we could
      demonstrate for the first time that it is possible to isolate intact DNA from
      cell-free bronchial lavage supernatants. Their quantity and quality are
      sufficient for further amplification via polymerase chain reaction. Altogether,
      tumor-associated changes were detected in the DNA of 47% of the patients that
      were analyzed.

PMID- 15251962
TI  - Therapy control in oncology by circulating nucleosomes.
AB  - The courses of circulating nucleosomes in the serum of patients with various
      solid tumors correlate with the clinical outcome after chemo- and radiotherapy.
      Already during the initial phase of treatment they showed considerable
      alterations consisting of a rapid increase followed by a decrease during the
      first therapeutic week. Among patients with advanced lung cancer undergoing
      chemotherapy, those patients who responded to therapy exhibited less pronounced
      increases and more complete decreases compared to those patients with
      insufficient response. In addition, response to therapy was correlated with
      stronger decreases of the precyclic baseline values from cycle 1 to 2 and from
      cycle 1 to 3. Thus, circulating nucleosomes are a valuable tool for the early
      prediction of therapeutic efficacy and can help to modulate therapy strategies
      early and on an individual basis.

PMID- 15251963
TI  - Extracellular DNA in breast cancer: Cell-surface-bound, tumor-derived
      extracellular DNA in blood of patients with breast cancer and nonmalignant
      tumors.
AB  - A methylation-specific polymerase chain reaction technique was used to
      investigate aberrant promoter methylation of RASSF1A and HIC-1 genes in
      circulating extracellular DNA (exDNA) from the blood of breast cancer and
      fibroadenoma patients. Methylated DNA could be detected in the exDNA eluted from
      the surface of erythrocytes and leukocytes, even in the samples where no
      methylated DNA could be detected in plasma. The data obtained demonstrate that
      cell surface bound exDNA provides a valuable source of material for early
      noninvasive cancer diagnostics and monitoring.

PMID- 15251964
TI  - Cell-surface-bound nucleic acids: Free and cell-surface-bound nucleic acids in
      blood of healthy donors and breast cancer patients.
AB  - Concentrations of extracellular DNA and RNA in the blood of healthy donors and
      patients with malignant and nonmalignant breast tumors were investigated. Cell
      surface-bound extracellular DNA and RNA were detached by PBS-EDTA treatment or
      mild trypsin treatment of erythrocytes and leukocytes. In healthy donors, almost
      all extracellular nucleic acids (98%) are bound at the surface of blood cells. In
      the blood of cancer patients, extracellular nucleic acids were found in plasma
      and not at the cell surface. In patients with nonmalignant breast tumors,
      extracellular nucleic acids were found both at the surface of blood cells and in
      plasma. In healthy donors, the cell-surface-bound DNA is represented by 20-kbp
      DNA fragments and smaller fragments that varied in amounts in different
      fractions.

PMID- 15251965
TI  - Mutant form of BRAF gene in blood plasma of cancer patients.

PMID- 15251966
TI  - Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients.
AB  - Recent evidence suggests that cell-free plasma DNA has potential use as a
      prognostic marker in many clinical settings. The aim of the present study was to
      evaluate the prognostic role of cell-free plasma DNA in the prediction of
      clinical outcome in intensive treatment unit (ITU) patients. Cell-free plasma DNA
      was measured by real-time polymerase chain reaction assay for the beta-globin
      gene and SOFA score, APACHE II score, CRP concentrations, and clinical outcome
      (duration of stay, ventilation time, and mortality) were noted in 94 patients on
      admission to the ITU. The median plasma DNA concentration in ITU patients was
      5493 GE/mL and this was significantly (P <0.001) higher than the DNA
      concentration in healthy subjects (1970 GE/mL). DNA concentration demonstrated a
      significant correlation with serum C-reactive protein (CRP) (r = 0.363)
      concentration and Sepsis-related Organ Failure Assessment (SOFA) (r = 0.360)
      score (P <0.001 for both by Pearson correlation) but not with Acute Physiology
      And Chronic Health Evaluation (APACHE II) score. Patients on ventilation had
      significantly higher DNA concentrations compared to nonventilated patients (7362
      GE/mL versus 4479 GE/mL; P = 0.004). The median DNA concentration in nonsurvivors
      was 9148 GE/mL, and this was 2.3-fold greater than that in survivors (3921 GE/ml,
      P <0.001). ROC analysis of the data indicated a sensitivity of 85% and a
      specificity of 80% when DNA concentration of 6109 GE/mL was taken as a predictor
      of death. The data suggest that cell-free plasma DNA concentration is potentially
      useful as a prognostic marker in ITU patients.

PMID- 15251967
TI  - Isolation of nucleic acid binding proteins: an approach for isolation of cell
      surface, nucleic acid binding proteins.
AB  - An approach for isolation of cell surface, nucleic acid binding proteins is
      described. This approach relies on affinity modification of the proteins of
      living cells with reactive oligonucleotides bearing a haptenic group. Covalently
      modified proteins were isolated by hapten-specific affinity chromatography with
      subsequent SDS-PAGE. Isolated 68-kDa proteins responsible for the binding of
      oligonucleotides were MS/MS sequenced and identified as keratin K1, keratin K10,
      keratin K2e, and albumin.

PMID- 15251968
TI  - Extracellular nucleic acids in cultures of long-term cultivated eukaryotic cells.
AB  - Investigation of the kinetics of nucleic acid release by HeLa (human cervical
      carcinoma cell line) and A431 (human squamous carcinoma cell line) cells is
      presented. The released DNA and RNA were shown to accumulate in culture medium
      and at the cell surface. A portion of cell surface bound RNA can be eluted with
      PBS/EDTA. Mild trypsin treatment is required for complete detachment of cell
      surface bound RNA and cell surface bound DNA. Electrophoretic analysis reveals
      characteristic patterns of cell-associated and free RNA and DNA molecules.

PMID- 15251969
TI  - High sensitivity scanning of colorectal tumors and matched plasma DNA for
      mutations in APC, TP53, K-RAS, and BRAF genes with a novel DHPLC fluorescence
      detection platform.
AB  - Tumor-associated DNA has been detected in plasma of colorectal cancer (CRC)
      patients using various techniques but with limited gene or mutation coverage. We
      report a highly sensitive scanning methodology for mutational assessment of the
      APC and TP53 genes, which typically pose an analytical challenge because of their
      significant genotypic heterogeneity as well as specific mutational scoring assays
      for K-RAS and BRAF. Plasma DNA isolated from 20 CRC patients were scanned for
      mutations in these targets without knowledge of the molecular or pathological
      analyses of the matched primary tumors. We chose mutation scanning technology and
      these molecular targets to provide a comprehensive screen for somatic mutations
      known to be associated with sporadic CRC. Mutations were identified with a novel
      denaturing high-performance liquid chromatography (DHPLC) platform that uses post
      separation fluorescence technology to enable the detection of variants that
      represent <0.1% of the total analyzed DNA. Mutant allele specific amplification
      (MASA) followed by detection with the same platform was used to identify low
      level target mutations (mutation scoring) in K-RAS codons 12, 13, and 61, and
      BRAF codon 599. Using this combined scanning and scoring approach, we were able
      to identify at least one mutational event in 20/20 (100%) CRC patients. The
      thoroughness of a mutation scanning and scoring panel may have important
      implications for CRC screening and disease monitoring during and following
      therapy.

PMID- 15251970
TI  - A new technology for mutation detection.
AB  - A sensitive, accurate, and simple method, called shifted termination assay (STA),
      was developed for detection of genetic mutations. The STA technology can be used
      to detect genetic mutations in polymerase chain reaction (PCR)-amplified samples
      of tissue, and plasma and serum that include circulating DNA containing point
      mutations, insertions, deletions, translocations, or single nucleotide
      polymorphisms (SNPs). STA is a multiple-base and multiple-cycle primer extension
      based detection method that can identify mutant DNA in samples containing as
      little as 1% mutant DNA in a mixture with 99% wild-type DNA. On the basis of the
      STA method, a mutation detection kit, called Mutector, was developed. Mutector is
      a 96-well microplate format test kit with colorimetric or luminescent detection
      options. An initial study shows that Mutector is more accurate and sensitive than
      sequencing and PCR restriction enzyme analysis methods in detecting DNA mutations
      from clinical samples.

PMID- 15251971
TI  - Clinical role of circulating Epstein-Barr virus DNA as a tumor marker in
      lymphoepithelioma-like carcinoma of the lung.
AB  - Nineteen Chinese patients with lymphoepithelioma-like carcinoma (LELC) of the
      lung were tested for Epstein-Barr virus (EBV) DNA in their serum samples by a
      quantitative polymerase chain reaction (PCR) technique. There was prospective
      serial monitoring of the serum in seven patients with advanced inoperable or
      relapsing disease. Five other patients at first diagnosis and two patients at
      relapse had only a single serum sample available. Serum samples were also taken
      from three other patients who had prior curative surgery and two patients with
      prolonged disease remission. Measurable levels of EBV DNA were detected in 11 of
      12 patients with a pre-therapy serum sample and a clinically evident tumor. A low
      level of EBV DNA was also detectable in one of the two other patients whose first
      serum samples were obtained after some chemotherapy. There was no detectable EBV
      DNA in the five patients without evidence of tumor. The longitudinal serum EBV
      DNA profile of seven patients showed consistent correlation with response to
      therapy and clinical outcome. Patients with a pre-therapy serum EBV DNA >10,000
      copies/mL had significantly inferior overall survival. This study suggests that
      circulating serum EBV DNA can be used as a tumor marker in the clinical
      management of patients with LELC of the lung.

PMID- 15251972
TI  - Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine
      therapy.
AB  - Lamivudine treatment of individuals with chronic HBV infection leads to a rapid
      decline of hepatitis B virus (HBV) serum DNA. Because HBV replication quickly
      reaches pretreatment values following cessation of the drug, we addressed the
      question of whether changes during therapy in composition and amount of
      discernible circulating viral DNA and RNA might provide an explanation for this
      phenomenon. Nucleic acids were extracted from serial serum samples of two
      chronically infected patients. The first patient was treated with lamivudine for
      14 weeks, whereas the second one, who displayed an HBV virus with a core gene
      mutation, received lamivudine for 10 weeks. Three sequence segments of the HBV
      genome synthesized successively during replication, namely, X, C, and X-preC,
      were analyzed via competitive polymerase chain reaction (PCR) and reverse
      transcriptase (RT)/PCR. HBV transcripts were also analyzed for differential
      polyadenylation. At the start of treatment, identical DNA copy numbers (10(9)/mL)
      were found for all three segments in the first patient. C segment DNA displayed
      the expected rapid decline. X-preC, a target contiguous only on plus-strand DNA,
      behaved similarly. In contrast, the X segment DNA copy numbers showed a less
      pronounced decrease, remaining at higher values (10(7)/mL) than the C and X-preC
      segments (both about 2 x 10(5)/mL) at the end of therapy. X segment RNA displayed
      a persisting copy number of about 10(7)/mL, whereas C and X-preC RNA decreased to
      about 10(5) copies/mL. Polyadenylated HBV RNA, both full-length and truncated,
      initially persisted at 10(5) but decreased to 10(4) to 10(3) copies/mL at the end
      of treatment. As expected, C segment DNA and RNA were not detected in the second
      patient, whereas X and X-preC segments showed essentially the same pattern as the
      first patient, although at a slightly lower level. We conclude that: (1) actual
      numbers of HBV genome equivalents during lamivudine therapy can be assessed only
      via X segment DNA, because it is reverse transcribed first; (2) lamivudine
      induces coexistence of DNA and RNA for the C and X segments at similar levels,
      indicating drug-arrested intermediates of reverse-transcribed HBV DNA minus
      strand; and (3) packaged HBV RNA lacks a poly(A) tail, whereas polyadenylated RNA
      is likely not packaged.

PMID- 15251973
TI  - Activation of HHV-6 in lymphoproliferative disorders: a polymerase chain reaction
      based study.
AB  - HHV-6 is a latent herpes virus persisting throughout the adult life of the
      infected host in an integrated form and is often activated in immunocompromised
      situations. Detection of HHV-6 DNA in the plasma of an individual indicates the
      presence of active viral replication in the host. Because lymphomas are known to
      be associated frequently with host immunosupression, we studied activation of HHV
      6 in 98 patients diagnosed with Hodgkin's disease (HD) or non-Hodgkin's lymphoma
      (NHL). HHV-6 activation was documented in 34% of cases of non-Hodgkin's lymphoma
      and 39% of those of Hodgkin's disease; however, no correlation of activation
      status with pathological types of Hodgkin's disease and between copy numbers in
      peripheral blood mononuclear cell DNA and the corresponding plasma DNA was
      noticeable.

PMID- 15251974
TI  - Cancer proteomics: Serum diagnostics for tumor marker discovery.
AB  - Cancer proteomics is an exciting field that is witnessing many new developments
      in recent years. It is hoped that these advances will result in decreased cancer
      death rates, which have not declined dramatically in the last several decades.
      Some of the problems with current tumor markers include the lack of sensitivity
      and specificity, factors that prevent their use in population-based screening of
      disease. Thus, there is an urgent need to identify novel biomarkers that can
      faithfully detect the disease state. As we are now in the post-genome era, many
      opportunities have been created. Genomic sequence data are available for human,
      as well as several other species. We are now poised to mine these data and to
      determine the functions of the encoded proteins constituting the human genome.
      Proteomics affords this opportunity by providing enhanced procedures and tools
      for discovery and also a framework for understanding these components in terms of
      pathogenesis. New technologies and improvements in existing methodologies will
      allow for the rapid growth in the identification and characterization of peptides
      and proteins that are unique to various clinical states. This technology can be
      successfully applied to clinical specimens for the identification of new tumor
      markers.

PMID- 15251975
TI  - Clinical proteomics and biomarker discovery.
AB  - Early detection of disease generally provides much-improved outcomes by a
      definitive medical procedure or through lifestyle modification along with
      specific medical management strategies. For serum biomarkers, which are central
      to the diagnosis of many diseases, to become truly useful sentinels of
      pathogenesis, their sensitivity and specificity in both early detection and
      recurrence monitoring must be improved. Currently, the detection and monitoring
      of disease markers is based on solitary proteins, and this approach is not always
      reliable. New classes of biomarkers derived from mass spectroscopy analysis of
      the low molecular weight proteome have shown improved abilities in the early
      detection of disease and hence in patient risk stratification and outcome. The
      development of a modular platform technology with sufficient flexibility and
      design abstractions allowing for concurrent experimentation, test, and refinement
      will help speed the progress of mass spectroscopy-derived proteomic pattern-based
      diagnostics from the scientific laboratory to the medical clinic. For acceptance
      by scientists, physicians, and regulatory personnel, new bioinformatic tools are
      essential system components for data management, analysis, and intuitive display
      of these new and complex data. Clinically engineered mass spectroscopy systems
      are essential for the further development and validation of multiplexed
      biomarkers that have shown tremendous promise for the early detection of disease.

PMID- 15251976
TI  - A serum proteomics approach to the diagnosis of ectopic pregnancy.
AB  - An ectopic pregnancy (EP) occurs when implantation of the embryo occurs outside
      of the uterus. If left untreated, the developing fetus will continue to grow,
      leading to life-threatening consequences for the mother. A major difficulty with
      the diagnosis of ectopic pregnancy is that methods of detection are limited, and
      some, such as ultrasound, are not very reliable in the earliest days of
      gestation. Currently, no effective serum test exists to distinguish an ectopic
      pregnancy from a normal intrauterine pregnancy. The incidence of ectopic
      pregnancy is increasing and has doubled in the last 20 years. It is now the
      second most common cause of maternal death in the first trimester of pregnancy.
      To address this issue, we initiated a project to identify serum markers of
      ectopic pregnancy. The subjects for these studies presented at the Hospital of
      the University of Pennsylvania. We obtained over 140 serum samples from women
      with suspected ectopic pregnancy: women presenting with pain and/or bleeding in
      the first trimester of pregnancy. The approximate racial breakdown of the
      subjects is as follows: African American, 36%; Caucasian, 3%; Asian, 2%;
      Hispanic, 1%; unknown, 58%. Serum samples from 139 women (62 with ectopic
      pregnancy and 77 with a normal intrauterine pregnancy) were applied to WCX2 (weak
      ion exchange) protein chip surfaces and analyzed for serum markers using surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF
      MS). Several proteins in the 7500-18,000 Da mass range were identified that may
      discriminate an ectopic pregnancy from an intrauterine pregnancy. The most
      promising markers were analyzed using classification and regression tree analysis
      (CART) with and without clinical variables (serum hCG value, length of
      amenorrhea). Two different algorithms were developed that classify the patients
      on the basis of sensitivity (number of EPs who screen positive/# of EPs) or
      specificity (# of healthy patients who screen negative/# of healthy). Our current
      approach is to refine these two "rule sets" to segregate patients into three
      groups: those who need immediate intervention for a probable ectopic pregnancy,
      those who appear to have a normal pregnancy, and those who need further
      monitoring for diagnosis.

PMID- 15251977
TI  - Detection of differentially expressed proteins in early-stage melanoma patients
      using SELDI-TOF mass spectrometry.
AB  - Tumor progression is a dynamic sequence of events that involves specific protein
      changes. We hypothesized that Surface Enhanced Laser Desorption/Ionization
      (SELDI) mass spectrometric analysis of sera from patients with AJCC stage I and
      II melanoma with negative loco-regional lymph nodes could identify potential
      melanoma-associated protein biomarkers of disease recurrence. Serum specimens
      were collected from 49 patients who developed recurrence (n = 25) or remained
      free of recurrence (n = 24) without evidence of disease following complete
      resection (AJCC stage I and II). Follow-up was longer than 5 years. Serum
      proteins were denatured and applied onto two protein chip chemistry surfaces
      (weak cationic WCX2; metal-binding, IMAC3-Cu). SELDI ProteinChip mass
      spectrometry was then performed. SELDI data were analyzed, protein peak
      clustering and classification were performed, and a supervised classification
      algorithm was employed to classify the dataset. Multiple protein peaks ranging
      from 3.3 to 30 kDa were identified between patients with recurrence and those
      without recurrence, and the expression pattern differences of three proteins were
      used to generate the discriminating classification tree. The biomarkers were
      expressed with a high degree of reproducibility. In this early characterization
      study, melanoma recurrence was predicted with a sensitivity of 72% (18/25) and a
      specificity of 75% (18/24). This novel pilot study revealed three proteins that
      accurately identified patients who developed recurrence after curative resection
      of primary melanoma.

PMID- 15251978
TI  - Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory
      chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is an important determinant of long
      term morbidity and mortality in allogeneic stem cell transplantation patients.
      Because cGVHD has clinical, histologic, and laboratory findings of autoimmune
      diseases and anti-B-cell therapy has shown efficacy in autoimmune diseases, we
      hypothesized that monoclonal anti-CD20 antibody therapy might improve patients
      with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD
      with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly
      dose of 375 mg/m(2) for 4 weeks. In case of incomplete clinical response,
      additional courses of 4 weeks were given. Five patients responded to treatment
      with marked clinical, biochemical, and histologic improvement. One patient failed
      to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A
      controlled trial is mandatory to confirm these results. The outcome of this study
      suggests a participating role of B cells in the pathogenesis of cGVHD.

PMID- 15251979
TI  - Improved outcome for children with acute lymphoblastic leukemia: results of Total
      Therapy Study XIIIB at St Jude Children's Research Hospital.
AB  - St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia
      (ALL) incorporated more stringent risk classification, early intensification of
      intrathecal chemotherapy, reinduction treatment, and the addition of
      dexamethasone to postremission therapy to increase the proportion of event-free
      survivors without jeopardizing their quality of life. Cranial irradiation was
      reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte
      count of 100 x 10(9)/L or more, or CNS-3 (5 or more leukocytes/microL with
      identifiable blast cells in an atraumatic sample or the presence of cranial nerve
      palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were
      classified as having lower-risk leukemia and received mainly antimetabolite-based
      continuation therapy; the 130 cases with higher-risk leukemia received more
      intensive continuation chemotherapy with multiple drug pairs administered in
      weekly rotation. The 5-year event-free survival estimate was 80.8% +/- 2.6% (SE);
      the 8-year rate was 78.6% +/- 5.8%. The 5-year cumulative risk of an isolated
      central nervous system (CNS) relapse was 1.7% +/- 0.8%, and that of isolated plus
      combined CNS relapse was 3.0% +/- 1.1%. The 5-year cumulative risks of etoposide
      related myeloid malignancies were 1.8% +/- 1.3% in the lower-risk patients who
      received a cumulative dose of 1.2 g/m(2) and 5.0% +/- 2.0% in the higher-risk
      patients who received a cumulative dose of up to 14.4 g/m(2) (P = .18).
      Independent adverse prognostic features included the presence of MLL-AF4 or BCR
      ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the
      6-week remission induction phase. Our results suggest the efficacy of early
      intensification of intrathecal chemotherapy and provide the basis for studies
      omitting cranial irradiation altogether.

PMID- 15251980
TI  - Imatinib mesylate (STI571) is a substrate for the breast cancer resistance
      protein (BCRP)/ABCG2 drug pump.
AB  - Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully
      used in the treatment of chronic myelogenous leukemia and gastrointestinal
      stromal tumors. However, the intended chronic oral administration of imatinib may
      lead to development of cellular resistance and subsequent treatment failure.
      Indeed, several molecular mechanisms leading to imatinib resistance have already
      been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined
      whether imatinib is a substrate for the breast cancer resistance protein
      (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a
      panel of well-defined BCRP-overexpressing cell lines, we provide the first
      evidence that imatinib is a substrate for BCRP, that it competes with
      mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by
      the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the
      gastrointestinal tract, BCRP might not only play a role in cellular resistance of
      tumor cells but also influence the gastrointestinal absorption of imatinib.

PMID- 15251981
TI  - STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic
      cells.
AB  - Interleukin-10-deficient (IL-10(-/-)) mice develop an IL-12-mediated intestinal
      inflammation in the absence of endogenous IL-10. The molecular mechanisms of the
      dysregulated IL-12 responses in IL-10(-/-) mice are poorly understood. In this
      study, we investigated the role of nuclear factor-kappa B (NF-kappaB) and signal
      transducers and activators of transcription 3 (STAT3) in lipopolysaccharide (LPS)
      induced IL-12p40 gene expression in bone marrow derived-dendritic cells (BMDCs)
      isolated from wild-type (WT) and IL-10(-/-) mice. We report higher IL-12p40 mRNA
      accumulation and protein secretion in LPS-stimulated BMDCs isolated from IL-10(-/
      ) compared with WT mice. LPS-induced NF-kappaB signaling is similar in IL-10(-/-)
      and WT BMDCs as measured by IkappaBalpha phosphorylation and degradation, RelA
      phosphorylation and nuclear translocation, and NF-kappaB transcriptional
      activity, with no down-regulatory effects of exogenous IL-10. Chromatin
      immunoprecipitation demonstrated enhanced NF-kappaB (cRel, RelA) binding to the
      IL-12p40 promoter in IL-10(-/-) but not WT BMDCs. Interestingly, LPS induced
      STAT3 phosphorylation in WT but not IL-10(-/-) BMDCs, a process blocked by IL-10
      receptor blocking antibody. Adenoviral gene delivery of a constitutively active
      STAT3 but not control green fluorescence protein (GFP) virus blocked LPS-induced
      IL-12p40 gene expression and cRel recruitment to the IL-12p40 promoter. In
      conclusion, dysregulated LPS-induced IL-12p40 gene expression in IL-10(-/-) mice
      is due to enhanced NF-kappaB recruitment to the IL-12p40 promoter in the absence
      of activated STAT3.

PMID- 15251983
TI  - Neuropsychologic changes from before transplantation to 1 year in patients
      receiving myeloablative allogeneic hematopoietic cell transplant.
AB  - Research indicates that myeloablative hematopoietic cell transplantation (HCT)
      impairs neurocognitive function. However, prospective studies on long-term
      effects are lacking. This longitudinal study examined neurocognitive changes over
      the first year in 142 adult recipients of allogeneic HC transplants who received
      neuropsychologic testing before transplantation and again after 80 days and 1
      year. Age-, sex-, and education-adjusted population-based standardized scores
      were used for normative comparisons. Performance on all tests declined from
      before transplantation to 80 days (P < .05) and improved by 1 year (P < .05),
      returning to pretransplantation levels on all tests except for grip strength and
      motor dexterity. Although verbal fluency and memory recovered by 1 year, both
      were below norms at all 3 testing times (P < .01). Logistic regressions indicated
      that patients without chemotherapy, other than hydroxyurea, previous to HCT and
      patients not receiving chronic graft-versus-host disease (GVHD) medication at 1
      year had lower risk of impaired function (P < .05). In conclusion, HCT was
      associated with significant generalized decline in neurocognitive performance at
      80 days, with subsequent recovery to pretransplantation levels by 1 year for most
      survivors, except on motor tasks. Results indicate that long-term cognitive
      decrements, as distinct from motor disabilities, infrequently derive directly
      from HCT.

PMID- 15251982
TI  - A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis
      during development.
AB  - Notch1 is known to play a critical role in regulating fates in numerous cell
      types, including those of the hematopoietic lineage. Multiple defects exhibited
      by Notch1-deficient embryos confound the determination of Notch1 function in
      early hematopoietic development in vivo. To overcome this limitation, we examined
      the developmental potential of Notch1(-/-) embryonic stem (ES) cells by in vitro
      differentiation and by in vivo chimera analysis. Notch1 was found to affect
      primitive erythropoiesis differentially during ES cell differentiation and in
      vivo, and this result reflected an important difference in the regulation of
      Notch1 expression during ES cell differentiation relative to the developing mouse
      embryo. Notch1 was dispensable for the onset of definitive hematopoiesis both in
      vitro and in vivo in that Notch1(-/-) definitive progenitors could be detected in
      differentiating ES cells as well as in the yolk sac and early fetal liver of
      chimeric mice. Despite the fact that Notch1(-/-) cells can give rise to multiple
      types of definitive progenitors in early development, Notch1(-/-) cells failed to
      contribute to long-term definitive hematopoiesis past the early fetal liver stage
      in the context of a wild-type environment in chimeric mice. Thus, Notch1 is
      required, in a cell-autonomous manner, for the establishment of long-term,
      definitive hematopoietic stem cells (HSCs).

PMID- 15251984
TI  - Dual role of phagocytic NADPH oxidase in bacterial killing.
AB  - The classical model of bacterial killing by phagocytic cells has been recently
      challenged by questioning the toxic effect of oxygen products and attributing the
      fundamental role to K(+) ions in releasing antimicrobial proteins within the
      phagosome. In the present study we followed O(2)(*-) production, changes of
      membrane potential, K(+) efflux, and bacterial killing in the presence of
      increasing concentrations of the nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor diphenylene iodonium. Efficiency of bacterial killing
      was assessed on the basis of bacterial survival measured by a new semiautomated
      method. Very low rates of O(2)(*-) production were accompanied by significant
      membrane depolarization and K(+) release and parallel improvement of bacterial
      killing. When O(2)(*-) production exceeded 20% of its maximal capacity, no
      further change was detected in the membrane potential and only minimal further
      K(+) efflux occurred, yet bacterial survival decreased parallel to the increase
      of O(2)(*-) production. The presented results indicate that both
      electrophysiological changes (depolarization and consequent ion movements) and
      the chemical effect of reactive oxygen species play a significant role in the
      killing of certain pathogens. The observation that an increase of membrane
      depolarization can compensate for decreased O(2)(*-) production may be important
      for potential therapeutic applications.

PMID- 15251985
TI  - Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation
      with disease activity and patient outcome.
AB  - BLyS, recently shown to be critical for survival of normal B cells, has been
      found to be elevated in a number of immune disease models. A role for BLyS in the
      survival of malignant B cells has also been revealed and we therefore sought to
      identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL). We
      found that tumor cells from all NHL histologic subtypes expressed one or more of
      3 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of
      expression was variable. We provide evidence that BLyS is expressed in tumors
      from patients with NHL and that BLyS levels increase as tumors transform to a
      more aggressive phenotype. Additionally, we provide evidence that serum BLyS
      levels are elevated in a subgroup of patients with NHL. In patients with de novo
      large B-cell lymphoma, a high BLyS level correlated with a poorer median overall
      survival, the presence of constitutional symptoms, and elevated values of lactic
      dehydrogenase. When BLyS levels were correlated with response to therapy in all
      patients, responding patients had a significantly lower BLyS level than those
      with progressive disease. In summary, we found that BLyS and its receptors
      represent a potentially important therapeutic target in B-cell lymphoma.

PMID- 15251986
TI  - A small proportion of mesenchymal stem cells strongly expresses functionally
      active CXCR4 receptor capable of promoting migration to bone marrow.
AB  - Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after
      transplantation, important for the correction of conditions such as metabolic
      storage disorders, can occur but with poor efficiency. Substantial improvements
      in engraftment will be required in order to derive a clinical benefit from MSC
      transplantation. Chemokines are the most important factors controlling cellular
      migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in
      promoting the migration of cells to the bone marrow, via its specific receptor
      CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its
      role in mediating migration to bone marrow. We show that CXCR4, although present
      at the surface of a small subset of MSCs, is important for mediating specific
      migration of these cells to bone marrow.

PMID- 15251988
TI  - Iron chelators with high antiproliferative activity up-regulate the expression of
      a growth inhibitory and metastasis suppressor gene: a link between iron
      metabolism and proliferation.
AB  - Iron (Fe) is critical for proliferation, but its precise role in cell cycle
      progression remains unclear. In this study, we examined the mechanisms involved
      by assessing the effects of Fe chelators on the expression of molecules that play
      key roles in this process. In initial studies, gene arrays were used to assess
      gene expression after incubating cells with 2 Fe chelators, namely,
      desferrioxamine (DFO) and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone
      (311), or the DNA-damaging agent, actinomycin D. From the genes assessed, only
      the N-myc downstream-regulated gene 1 (Ndrg1) was specifically up-regulated by Fe
      chelation. Although the function of Ndrg1 is unclear, previous studies showed it
      markedly slows tumor growth and acts as a potent metastasis suppressor.
      Incubation of cells with chelators markedly increased Ndrg1 mRNA and protein
      expression, but this was not found with their Fe complexes or when the Fe-binding
      site had been inactivated. Increased Ndrg1 expression following Fe chelation was
      related to the permeability and antiproliferative activity of chelators and could
      be reversed by Fe repletion. Moreover, Ndrg1 up-regulation after chelation
      occurred at the transcriptional level and was mediated by hypoxia inducible
      factor-1alpha (HIF-1alpha)-dependent and -independent mechanisms. Our
      investigation suggests Ndrg1 is a novel link between Fe metabolism and the
      control of proliferation.

PMID- 15251987
TI  - Gene expression profiles at diagnosis in de novo childhood AML patients identify
      FLT3 mutations with good clinical outcomes.
AB  - Fms-like tyrosine kinase 3 (FLT3) mutations are associated with unfavorable
      outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays
      to identify gene expression profiles related to FLT3 status and outcome in
      childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MUs),
      24 with internal tandem duplications (ITDs) and 12 with activating loop mutations
      (ALMs). In addition, 8 of 19 specimens from patients with relapses had FLT3-MUs.
      Predictive analysis of microarrays (PAM) identified genes that differentiated
      FLT3-ITD from FLT3-ALM and FLT3 wild-type (FLT3-WT) cases. Among the 42 specimens
      with FLT3-MUs, PAM identified 128 genes that correlated with clinical outcome.
      Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45%
      versus 5% for those with an unfavorable signature (P = .018). Among FLT3-MU
      specimens, high expression of the RUNX3 gene and low expression of the ATRX gene
      were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was
      used to classify FLT3-MU cases into 3 EFS groups: 70%, 37%, and 0% for low,
      intermediate, and high ratios, respectively (P < .0001). Thus, gene expression
      profiling identified AML patients with divergent prognoses within the FLT3-MU
      group, and the RUNX3 to ATRX expression ratio should be a useful prognostic
      indicator in these patients.

PMID- 15251989
TI  - Limits of HLA mismatching in unrelated hematopoietic cell transplantation.
AB  - HLA matching between the donor and recipient improves the success of unrelated
      hematopoietic cell transplantation (HCT). Matched donors are available for only a
      minority of patients. Further information is needed to evaluate the limits of HLA
      mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1,
      and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for
      treatment of a marrow disorder. A single HLA allele or antigen mismatch was
      associated with increased mortality among patients with chronic myeloid leukemia
      (CML) within 2 years after diagnosis compared to patients with no HLA mismatch,
      but not among those with more advanced malignancy. In particular, a single HLA-C
      mismatch conferred increased risk of mortality compared to matches. There was a
      suggestion for increased mortality with multiple mismatches involving HLA-DQB1
      compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA
      allele or antigen mismatch may be used for HCT when a fully matched donor is not
      available for patients with diseases that do not permit time for a lengthy
      search. Whenever possible, HLA-C mismatches should be avoided for patients with
      early stage CML, and HLA-DQB1 mismatches should be avoided for patients with
      multiple mismatches.

PMID- 15251990
TI  - A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by
      inhibiting caspase 8 activation.
AB  - A20 is a stress response gene in endothelial cells (ECs). A20 serves a dual
      cytoprotective function, protecting from tumor necrosis factor (TNF)-mediated
      apoptosis and inhibiting inflammation via blockade of the transcription factor
      nuclear factor-kappaB (NF-kappaB). In this study, we evaluated the molecular
      basis of the cytoprotective function of A20 in EC cultures and questioned whether
      its protective effect extends beyond TNF to other apoptotic and necrotic stimuli.
      Our data demonstrate that A20 targets the TNF apoptotic pathway by inhibiting
      proteolytic cleavage of apical caspases 8 and 2, executioner caspases 3 and 6,
      Bid cleavage, and release of cytochrome c, thus preserving mitochondrion
      integrity. A20 also protects from Fas/CD95 and significantly blunts natural
      killer cell-mediated EC apoptosis by inhibiting caspase 8 activation. In addition
      to protecting ECs from apoptotic stimuli, A20 safeguards ECs from complement
      mediated necrosis. These data demonstrate, for the first time, that the
      cytoprotective effect of A20 in ECs is not limited to TNF-triggered apoptosis.
      Rather, A20 affords broad EC protective functions by effectively shutting down
      cell death pathways initiated by inflammatory and immune offenders.

PMID- 15251991
TI  - A (pain free) step in the right direction.

PMID- 15251992
TI  - The king of the blind extends his frontiers.

PMID- 15251993
TI  - Corticosteroids for septic shock--a standard of care?

PMID- 15251994
TI  - Chronic adhesive arachnoiditis.

PMID- 15251995
TI  - Anaesthetists understand their work in different ways.

PMID- 15251996
TI  - Accreditation in transoesophageal echocardiography.

PMID- 15251997
TI  - Hypertension and perioperative risk.

PMID- 15251998
TI  - Remifentanil is too potent to be given by bolus.

PMID- 15251999
TI  - Intraoperative i.v. morphine reduces pain scores and length of stay in the post
      anaesthetic care unit after thyroidectomy.

PMID- 15252000
TI  - Quality of in-hospital care in acute coronary syndromes: it is time to close the
      gap.

PMID- 15252001
TI  - Optimising care of acute coronary syndromes in three Australian hospitals.
AB  - OBJECTIVE: To improve quality of in-hospital care of patients with acute coronary
      syndromes using a multifaceted quality improvement program. DESIGN: Prospective,
      before and after study of the effects of quality improvement interventions
      between October 2000 and August 2002. Quality of care of patients admitted
      between 1 October 2000 and 16 April 2001 (baseline) was compared with that of
      those admitted between 15 February 2002 and 31 August 2002 (post-intervention).
      SETTING: Three teaching hospitals in Brisbane, Australia. STUDY PARTICIPANTS:
      Consecutive patients (n = 1594) admitted to hospital with acute coronary syndrome
      [mean age 68 years (SD 14 years); 65% males]. INTERVENTIONS: Clinical guidelines,
      reminder tools, and educational interventions; 6-monthly performance feedback;
      pharmacist-mediated patient education program; and facilitation of
      multidisciplinary review of work practices. MAIN OUTCOME MEASURES: Changes in key
      quality indicators relating to timing of electrocardiogram (ECG) and thrombolysis
      in emergency departments, serum lipid measurement, prescription of adjunctive
      drugs, and secondary prevention. RESULTS: Comparing post-intervention with
      baseline patients, increases occurred in the proportions of eligible patients:
      (i) undergoing timely ECG (70% versus 61%; P = 0.04); (ii) prescribed angiotensin
      converting enzyme inhibitors (70% versus 60%; P = 0.002) and lipid-lowering
      agents (77% versus 68%; P = 0.005); (iii) receiving cardiac counselling in
      hospital (57% versus 48%; P = 0.009); and (iv) referred to cardiac rehabilitation
      (17% versus 8%; P < 0.001). CONCLUSIONS: Multifaceted approaches can improve care
      processes for patients hospitalized with acute coronary syndromes. Care processes
      under direct clinician control changed more quickly than those reliant on complex
      system factors. Identifying and overcoming organizational impediments to quality
      improvement deserves greater attention.

PMID- 15252002
TI  - Therapy outcome measures for allied health practitioners in Australia: the
      AusTOMs.
AB  - OBJECTIVE: The aim of this study was to develop a valid and reliable measure of
      therapy outcome for three allied health professions in Australia: speech
      pathology, occupational therapy, and physiotherapy. The Australian Therapy
      Outcome Measures (AusTOMs) enable measurement of the differences in client
      profiles and patterns of services provision across health care settings. In this
      paper we describe phase 1 of the study: the development and preliminary
      validation of the AusTOMs. METHOD: The UK TOMs, developed by Enderby, were
      scrutinized by the research team. A pilot core scale was developed, based on the
      structure of the TOM. Focus groups of expert clinicians for each profession,
      across the state of Victoria in Australia, analysed and refined the scales
      further. A mail-out survey was then sent to therapists across Australia to assess
      both face and content validity of the AusTOMs. MAIN RESULTS: A new tool, the
      AusTOM, was developed and tailored to the needs of each profession, with input
      from specialist clinicians and allied health researchers. The face and content
      validity of the new scales were assessed, and good consensus was obtained for the
      wording and content validity of the scales. The discriminative validity,
      concurrent validity, and reliability of the tool are now being evaluated.
      CONCLUSION: We have produced an outcome measure in the Australian context for
      speech pathology, physiotherapy, and occupational therapy. There are six speech
      pathology scales, nine physiotherapy scales, and 11 occupational therapy scales
      in the AusTOMs. A clinician chooses the relevant scale(s) for the client (based
      on the goals of therapy) and makes a rating across all domains for each scale.
      Further papers will report on the reliability, validity, and clinical usefulness
      of the AusTOMs.

PMID- 15252003
TI  - Variations in risk-adjusted outcomes in a managed acute/long-term care program
      for frail elderly individuals.
AB  - OBJECTIVE: To develop and investigate the properties of three performance
      measures based on risk-adjusted health outcomes for a frail, elderly, community
      dwelling population enrolled in a managed, acute, and long-term care program.
      DESIGN: Retrospective analyses of an administrative dataset containing individual
      level records with information about socioeconomics, health, functional and
      cognitive status, diagnoses, and treatments. We estimated risk-adjustment models
      predicting mortality, decline in functional status, and decline in self-assessed
      health. Each model includes individual risk factors and indicator variables for
      the program site in which the individual enrolled. Sites were ranked based on
      their performance in each risk-adjusted outcome, and the properties of these
      performance measures were investigated. SETTING: Twenty-eight sites of the
      Program of All-Inclusive Care for the Elderly (PACE) that provide primary, acute,
      and long-term care services under capitated Medicare and Medicaid payment to a
      nursing home certifiable, and functionally and cognitively frail community
      dwelling elderly population. STUDY PARTICIPANTS: Three thousand one hundred and
      thirty-eight individuals who were newly enrolled between 1 January 1998 and 31
      December 1999. The average age of these enrollees was 78 years, 27% were male,
      50% were diagnosed with dementia, and they had approximately 4 Activities of
      Daily Living limitations and 7.4 Instrumental Activities of Daily Living
      limitations. MAIN OUTCOME MEASURES: Risk-adjustment models, performance ranking
      for each site, and correlations between performance rankings. RESULTS: We present
      risk-adjustment models for mortality, change in functional status, and self
      assessed health status. We found substantial variation across sites in
      performance, but no correlation between performance with respect to different
      outcomes. CONCLUSIONS: The variations in outcomes suggest that sites can improve
      their performance by learning from the practices of those with the best outcomes.
      Further research is required to identify processes of care that lead to best
      outcomes.

PMID- 15252004
TI  - Injection practices in Burkina Faso in 2000.
AB  - BACKGROUND: Unsafe delivery and overuse of injections can result in the spread of
      hepatitis B virus, hepatitis C virus, and HIV. The aim of the present survey was
      to estimate the frequency of safe injection practices in Burkina Faso. METHOD:
      Using the new standardized World Health Organization tool to assess injection
      practices, we selected 80 primary health facilities with a two-stage cluster
      sampling method, collected information using structured observations and provider
      interviews, and analyzed the data using Epi-Info software. RESULTS: We observed
      116 injections in 52 facilities. In 50 facilities [96%; 95% confidence interval
      (CI) 85-99%] injections were given with a new, single-use syringe and needle. In
      29 facilities (56%; 95% CI 36-74%), staff recapped needles using two hands. All
      80 facilities visited had a stock in the community to provide new, single-use
      syringes and needles. In 61% (95% CI 54-79%) of facilities, staff reported
      needlestick injuries in the last 12 months. Used needles were discarded in open
      containers in 66 facilities (83%; 95% CI 55-96%) and observed in the surroundings
      of 46 facilities (57%; 95% CI 32-80%). CONCLUSIONS: In 2000, most of the health
      facilities in Burkina Faso were using sterile injection equipment. However,
      practices were still observed that could expose patients, health care workers,
      and communities to risks, and that required specific interventions.

PMID- 15252005
TI  - A randomized controlled trial of league tables and control charts as aids to
      health service decision-making.
AB  - OBJECTIVES: Health service managers and other decision-makers are required to act
      on the basis of data. Little attention has been paid to the effects of data
      presentation on the decisions taken. This study uses a randomized controlled
      trial design to investigate the effects of two forms of data presentation--league
      tables and control charts--on health service decision-makers. METHODS: Directors
      of public health in 122 health authorities in the UK were mailed three case
      studies and a questionnaire. The case studies showed data on variations in
      mortality by health service provider. The questionnaire asked them to indicate
      whether they would take action as a result of the data and to identify the health
      service providers on whom they would take action. Participants were randomly
      allocated to receive the same data in the form of ranked histograms (league
      tables) or control charts. MAIN OUTCOME MEASURE: The percentage of participants
      who would take action on health service providers. RESULTS: Fifty-seven
      questionnaires were returned. For each case study, respondents receiving data as
      league tables stated they would take action on significantly more health service
      providers than those receiving data as control charts: for the first case study,
      the percentages were 3.3% versus 1.8% (P < 0.001) for league tables and control
      charts, respectively; for the second case study, 15.9% versus 6.7% (P = 0.029),
      respectively; and for the third, 5.9% versus 0.7% (P = 0.002), respectively.
      Respondents receiving data as league tables were significantly more likely to
      request further information on case mix. CONCLUSIONS: Compared with league
      tables, health service decision-makers identify fewer outliers for further action
      when performance data are presented as control charts. They also reduce the
      tendency to request further information. Using control charts rather than league
      tables for the routine presentation of comparative data would reduce over
      investigation of unusual performance.

PMID- 15252006
TI  - What makes an error unacceptable? A factorial survey on the disclosure of medical
      errors.
AB  - BACKGROUND: Although the importance of disclosing medical errors to patients has
      been argued, little is known about the relative effect of different attributes of
      error handling and communication on patients' judgments about errors. OBJECTIVES:
      This study investigates how different characteristics of medical errors and of
      physicians' subsequent handling of errors contribute to patients' evaluations of
      the incident and their attitudes towards potential consequences and sanctions for
      the physician. MATERIALS AND METHODS: A factorial survey using the vignette
      technique presented hypothetical scenarios involving medical errors to members of
      the general public in an Internet-based study. Members of a German Internet
      survey panel participated (n = 1017). Multiple ordered logistic regression models
      were estimated to explain citizens' judgments of error severity and their
      attitudes towards reporting of errors, wishing for referral to another physician,
      and supporting sanctions against the health professional involved as a response
      to characteristics of the presented errors. RESULTS: While the severity of the
      outcomes of errors remains the most important single factor in the choice of
      actions to be taken, the professional's approach to the error is regarded as
      essential in the overall evaluation of errors and the consideration of
      consequences. In errors with a severe outcome, an honest, empathic, and
      accountable approach to the error decreases the probability of participants'
      support for strong sanctions against the physician involved by 59%. Judgments
      were only marginally affected by respondents' characteristics. CONCLUSIONS: The
      handling of errors strongly contributes to citizens' choice of actions to be
      taken, and they are sensitive to failures to name the incident as an 'error'. For
      the success of de-individualized, systems-oriented approaches to errors,
      communication of clear accountability to patients will be crucial.

PMID- 15252007
TI  - Effect of a clinical practice guideline on physician compliance.
AB  - OBJECTIVES: To evaluate the effect of a clinical practice guideline for cesarean
      section due to dystocia on physician compliance, pregnancy outcome, and cesarean
      delivery rates, and to identify factors associated with physician non-compliance.
      DESIGN: A cross-sectional study. SETTING: A university hospital, Southern
      Thailand. STUDY PARTICIPANTS: All 719 medical records of women undergoing a
      cesarean section due to dystocia (failure to progress; cephalopelvic
      disproportion) before and after implementation of the guideline, from 1 January
      1998 to 31 December 2000. INTERVENTION: A clinical practice guideline for
      cesarean section due to dystocia was implemented on 1 June 1999. MAIN OUTCOME
      MEASURES: Physician compliance, pregnancy outcomes, and cesarean section rates.
      Multivariate logistic regression was used to identify factors associated with
      physician non-compliance. Independent variables consisted of maternal age,
      height, parity, type of service, and birthweight. RESULTS: Physician compliance
      with the guideline was 89.2%. Maternal complications were less in the period
      after implementation of the guideline. Fetal outcomes were not different between
      the two periods. The cesarean section rates due to dystocia decreased after
      implementation of the guideline, from 10.7% in 1999 to 8.6% in 2002. Private
      practice, maternal short stature, and birthweight > or = 3500 g were significant
      predictors of physician non-compliance. CONCLUSIONS: Physician compliance was
      high. A clinical practice guideline can reduce the cesarean section rates due to
      dystocia without increasing adverse outcomes. Physician non-compliance was more
      common in women with well known risk for cephalopelvic disproportion, and private
      practice.

PMID- 15252008
TI  - Evaluation of a labeling system to indicate the presence of an advance directive
      in a hospital medical record.
AB  - OBJECTIVE: To investigate the accuracy of one hospital's system to indicate
      whether an advance directive exists within a patient's medical record. DESIGN:
      Medical record review while patients were hospitalized. SETTING: Internal
      medicine residency program within a tertiary care hospital. STUDY PARTICIPANTS:
      Patients admitted to four internal medicine services between 25 October 2000 and
      6 December 2000. MAIN OUTCOME MEASURES: Presence of an advance directive and a
      label in medical records were recorded, along with patient demographics, and
      sensitivity, specificity, and accuracy were calculated. RESULTS: Four of 125
      medical records (3%) contained advance directives. Sensitivity of a label for an
      advance directive was 25% [95% confidence interval (CI) 1-81%], specificity was
      62% (95% CI 53-71%), and accuracy was 61% (95% CI 52-69%). CONCLUSIONS: Use of
      the hospital's labeling system to indicate the presence of advance directives was
      found to be highly inaccurate. Failure to correctly follow or understand the
      intended labeling procedure was the most likely source of error. Hospitals should
      include plans to check the accuracy of protocols when they are adopted to ensure
      that they are performing as intended.

PMID- 15252009
TI  - A novel dynamin-associating molecule, formin-binding protein 17, induces tubular
      membrane invaginations and participates in endocytosis.
AB  - Dynamin associates with a variety of SH3 domain-containing molecules via a C
      terminal proline-rich motif and takes part, with them, in endocytic processes.
      Here, we have investigated a new dynamin-associating molecule, formin-binding
      protein 17 (FBP17), involved in deforming the plasma membrane and in endocytosis.
      FBP17 formed tubular invaginations originating from the plasma membrane. Its N
      terminal Fer/CIP4 homology domain, a coiled-coil domain, and a proline-rich motif
      were required for tubular invagination and self-assembly, by which tubular
      invagination might be induced. Using anti-FBP17 antibody, we detected positive
      immunoreactions in the testis that were restricted to the germ cells. We also
      detected FBP17 in the brain by immunoblotting and in situ hybridization. When COS
      cells expressing enhanced green fluorescent protein-tagged FBP17 were incubated
      with fluorescently labeled transferrin, epidermal growth factor, and cholera
      toxin, these molecules co-localized with FBP17-induced tubular invaginations,
      suggesting that FBP17 is involved in dynamin-mediated endocytosis in both a
      clathrin-dependent and -independent manner. These observations therefore indicate
      that FBP17 interacts with dynamin and regulates endocytosis by forming
      vesicotubular structures.

PMID- 15252010
TI  - The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is
      mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively
      activated receptor (CAR).
AB  - Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically
      relevant drug interactions. In contrast with other CYP3A family members, studies
      on the inducibility of CYP3A5 indicate conflicting results. We report the
      induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin.
      Furthermore, induction of CYP3A5 mRNA was observed in intestinal biopsies in
      three of eight probands following exposure to the antibiotic. The highest
      absolute levels of CYP3A5 transcripts were found following rifampin treatment in
      hepatocytes and intestines from carriers of CYP3A5*1 alleles. Elucidation of the
      mechanism involved in CYP3A5 induction revealed that constitutively activated
      receptor (CAR) and pregnane X receptor (PXR) transactivated the CYP3A5 promoter (
      688 to +49) and that the transactivation was dependent on an everted repeat
      separated by 6 bp (ER6-dependent). Treatment with the prototypical PXR ligand
      rifampin led to a 2-fold induction of the CYP3A5 promoter activity. In agreement
      with these observations, PXR and CAR bound specifically to the ER6 motif. Hepatic
      expression of PXR correlated with that of CYP3A5 mRNA levels in a bank of liver
      samples. Taken together, studies here revealed the presence of a functional ER6
      motif in the CYP3A5 promoter located -100 bp upstream from the transcription
      start site, suggesting that CYP3A5 is inducible by mechanisms similar to those
      involved in CYP3A4 induction. Enhanced expression of CYP3A5 caused by exposure to
      inducers may phenocopy the effects of the high expression allele CYP3A5*1. In
      this manner, induction of CYP3A5 may contribute to the overall importance of this
      P450 in drug metabolism and drug interactions.

PMID- 15252011
TI  - Regulation of the coupling to different G proteins of rat corticotropin-releasing
      factor receptor type 1 in human embryonic kidney 293 cells.
AB  - The regulation of G protein activation by the rat corticotropin-releasing factor
      receptor type 1 (rCRFR1) in human embryonic kidney (HEK)293 (HEK-rCRFR1) cell
      membranes was studied. Corresponding to a high and low affinity ligand binding
      site, sauvagine and other peptidic CRFR1 ligands evoked high and low potency
      responses of G protein activation, differing by 64-fold in their EC(50) values as
      measured by stimulation of [(35)S]GTPgammaS binding. Contrary to the low potency
      response, the high potency response was of lower GTPgammaS affinity, pertussis
      toxin (PTX)-insensitive, and homologously desensitized. Distinct desensitization
      was also observed in the adenylate cyclase activity, when its high potency
      stimulation was abolished and the activity became low potently inhibited by
      sauvagine. From these results and immunoprecipitation of [(35)S]GTPgammaS-bound
      Galpha(s) and Galpha(i) subunits it is concluded that the high and low potency
      [(35)S]GTPgammaS binding stimulation reflected coupling to G(s) and G(i)
      proteins, respectively, only G(s) coupling being homologously desensitized.
      Immunoprecipitation of [(35)S]GTPgammaS-bound Galpha(q/11) revealed additional
      coupling to G(q/11), which also was homologously desensitized. Although
      Galpha(q/11) coupling was PTX-insensitive, half of the sauvagine-stimulated
      accumulation of inositol phosphates in the cells was PTX-sensitive, suggesting
      involvement of G(i) in addition to G(q/11)in the stimulation of inositol
      metabolism. It is concluded that CRFR1 signals through at least two different
      ways, one leading to G(s)- and G(q/11)-mediated signaling steps and
      desensitization and another leading to G(i) -mediated signals without being
      desensitized. Furthermore, the concentrations of the stimulating ligand and GTP
      and desensitization may be part of a regulatory mechanism determining the actual
      ratio of the coupling of CRFR1 to different G proteins.

PMID- 15252012
TI  - Abscisic acid signaling through cyclic ADP-ribose in hydroid regeneration.
AB  - Cyclic ADP-ribose (cADPR) is an intracellular calcium (Ca(2+)(i)) mobilizer
      involved in fundamental cell functions from protists to higher plants and
      mammals. Biochemical similarities between the drought-signaling cascade in plants
      and the temperature-sensing pathway in marine sponges suggest an ancient
      evolutionary origin of a signaling cascade involving the phytohormone abscisic
      acid (ABA), cADPR, and Ca(2+)(i). In Eudendrium racemosum (Hydrozoa, Cnidaria),
      exogenously added ABA stimulated ADP-ribosyl cyclase activity via a protein
      kinase A (PKA)-mediated phosphorylation and increased regeneration in the dark to
      levels observed under light conditions. Light stimulated endogenous ABA
      synthesis, which was conversely inhibited by the inhibitor of plant ABA synthesis
      Fluridone. The signal cascade of light-induced regeneration uncovered in E.
      racemosum: light --> increasing ABA --> PKA --> cyclase activation --> increasing
      [cADPR](i) --> increasing [Ca(2+)](i) --> regeneration is the first report of a
      complete signaling pathway in Eumetazoa involving a phytohormone.

PMID- 15252013
TI  - Ezrin/radixin/moesin proteins are high affinity targets for ADP-ribosylation by
      Pseudomonas aeruginosa ExoS.
AB  - Pseudomonas aeruginosa ExoS is a bifunctional type III-secreted cytotoxin. The N
      terminus (amino acids 96-233) encodes a GTPase-activating protein activity,
      whereas the C terminus (amino acids 234-453) encodes a factor-activating ExoS
      dependent ADP-ribosyltransferase activity. The GTPase-activating protein activity
      inactivates the Rho GTPases Rho, Rac, and Cdc42 in cultured cells and in vitro,
      whereas the ADP-ribosylation by ExoS is poly-substrate-specific and includes Ras
      as an early target for ADP-ribosylation. Infection of HeLa cells with P.
      aeruginosa producing a GTPase-activating protein-deficient form of ExoS rounded
      cells, indicating the ADP-ribosyltransferase domain alone is sufficient to elicit
      cytoskeletal changes. Examination of substrates modified by type III-delivered
      ExoS identified a 70-kDa protein as an early and predominant target for ADP
      ribosylation. Matrix-assisted laser desorption ionization mass spectroscopy
      identified this protein as moesin, a member of the ezrin/radixin/moesin (ERM)
      family of proteins. ExoS ADP-ribosylated recombinant moesin at a linear velocity
      that was 5-fold faster and with a K(m) that was 2 orders of magnitude lower than
      Ras. Moesin homologs ezrin and radixin were also ADP-ribosylated, indicating the
      ERMs collectively represent high affinity targets of ExoS. Type III delivered
      ExoS ADP-ribosylated moesin and ezrin (and/or radixin) in cultured HeLa cells.
      The ERM proteins contribute to cytoskeleton dynamics, and the ability of ExoS to
      ADP-ribosylate the ERM proteins links ADP-ribosylation with the cytoskeletal
      changes associated with ExoS intoxication.

PMID- 15252014
TI  - A signal peptide peptidase (SPP) reporter activity assay based on the cleavage of
      type II membrane protein substrates provides further evidence for an inverted
      orientation of the SPP active site relative to presenilin.
AB  - Signal peptide peptidase (SPP) is an intramembrane-cleaving protease identified
      by its cleavage of several type II membrane signal peptides after signal
      peptidase cleavage. Here we describe a novel, quantitative, cell-based SPP
      reporter assay. This assay utilizes a substrate consisting of the NH2 terminus of
      the ATF6 transcription factor fused to a transmembrane domain susceptible to SPP
      cleavage in vitro. In cells, cleavage of the substrate releases ATF6 from the
      membrane. This cleavage can be monitored by detection of an epitope that is
      unmasked in the cleaved substrate or by luciferase activity induced by the
      cleaved ATF6 substrate binding to and activating an ATF6 luciferase reporter
      construct. Using this assay we show that (i) SPP is the first aspartyl
      intramembrane-cleaving protease whose activity increases proportionally to its
      overexpression and (ii) selectivity of various SPP and gamma-secretase inhibitors
      can be rapidly evaluated. Because this assay was designed based on data
      suggesting that SPP has an orientation distinct from presenilin and cleaves type
      II membrane proteins, we determined whether the segment of SPP located between
      the two presumptive catalytic aspartates was in the lumen or cytoplasm. Using
      site-directed mutagenesis to insert an N-linked glycosylation site we show that a
      portion of this region is present in the lumen. These data provide strong
      evidence that although the SPP and presenilin active sites have some
      similarities, their presumptive catalytic domains are inverted. This assay should
      prove useful for additional functional studies of SPP as well as evaluation of
      SPP and gamma-secretase inhibitors.

PMID- 15252015
TI  - Regulation of the cell surface expression and function of angiotensin II type 1
      receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac
      myocytes.
AB  - Rab1 GTPase coordinates vesicle-mediated protein transport specifically from the
      endoplasmic reticulum (ER) to the Golgi apparatus. We recently demonstrated that
      Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R)
      to the cell surface in HEK293 cells and that transgenic mice overexpressing Rab1
      in the myocardium develop cardiac hypertrophy. To expand these studies, we
      determined in this report whether the modification of Rab1-mediated ER-to-Golgi
      transport can alter the cell surface expression and function of endogenous AT1R
      and AT1R-mediated hypertrophic growth in primary cultures of neonatal rat
      ventricular myocytes. Adenovirus-mediated gene transfer of wild-type Rab1
      (Rab1WT) significantly increased cell surface expression of endogenous AT1R in
      neonatal cardiomyocytes, whereas the dominant-negative mutant Rab1N124I had the
      opposite effect. Brefeldin A treatment blocked the Rab1WT-induced increase in
      AT1R cell surface expression. Fluorescence analysis of the subcellular
      localization of AT1R revealed that Rab1 regulated AT1R transport specifically
      from the ER to the Golgi in HL-1 cardiomyocytes. Consistent with their effects on
      AT1R export, Rab1WT and Rab1N124I differentially modified the AT1R-mediated
      activation of ERK1/2 and its upstream kinase MEK1. More importantly, adenovirus
      mediated expression of Rab1N124I markedly attenuated the Ang II-stimulated
      hypertrophic growth as measured by protein synthesis, cell size, and sarcomeric
      organization in neonatal cardiomyocytes. In contrast, Rab1WT expression augmented
      the Ang II-mediated hypertrophic response. These data strongly indicate that AT1R
      function in cardiomyocytes can be modulated through manipulating AT1R traffic
      from the ER to the Golgi and provide the first evidence implicating the ER-to
      Golgi transport as a regulatory site for control of cardiomyocyte growth.

PMID- 15252016
TI  - A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to
      acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi.
AB  - We cloned an aquaporin gene from Trypanosoma cruzi (TcAQP) that encodes a protein
      of 231 amino acids, which is highly hydrophobic. The protein has six putative
      transmembrane domains and the two signature motifs asparagine-proline-alanine
      (NPA) which have been shown, in other aquaporins, to be involved in the formation
      of an aqueous channel spanning the bilayer. TcAQP was sensitive to endo H
      treatment, suggesting that the protein is N-glycosylated. Oocytes of Xenopus
      laevis expressing TcAQP swelled under hyposmotic conditions indicating water
      permeability, which was abolished after preincubating oocytes with very low
      concentrations of the AQP inhibitors HgCl(2) and AgNO(3). glycerol transport was
      detected. No Immunofluorescence microscopy of T. cruzi expressing GFP-TcAQP
      showed co-localization of TcAQP with the vacuolar proton pyrophosphatase (V-H(+)
      PPase), a marker of acidocalcisomes. This localization was confirmed by Western
      blotting and immunofluorescence staining using polyclonal antibodies against a C
      terminal peptide of TcAQP. In addition, there was a strong anterior labeling in a
      vacuole, close to the flagellar pocket, that was distinct from the
      acidocalcisomes and that was identified by immunogold electron microscopy as the
      contractile vacuole complex. Taking together, the presence of an aquaporin in
      acidocalcisomes and the contractile vacuole complex of T. cruzi, provides support
      for the role of these organelles in osmotic adaptations of these parasites.

PMID- 15252017
TI  - The role of the conserved glycines of ATP-binding cassette signature motifs of
      MRP1 in the communication between the substrate-binding site and the catalytic
      centers.
AB  - A key element of the structural model of ABC-ATP-ases is the interaction of the
      two ABC domains. They complement each other's active sites in a way that the ABC
      signature motif (LSGGQ) of one subunit interacts with the gamma-phosphate of the
      ATP, bound at the Walker motifs of the opposite subunit. In the present study,
      the conserved glycines in the fourth position of the LSGGQ motifs of human MRP1
      were substituted for aspartic acids (G771D and G1433D), the mutants were
      expressed in Sf9 insect cells, and the nucleotideas well as the transported
      substrate-protein interactions were studied. We found that these transport- and
      ATPase-incompetent mutants showed no nucleotide trapping under any of the
      conditions examined. However, when measuring the effect of nucleotide and
      transported substrates on the vanadate-induced cleavage reactions, we found that
      the effect of substrates on the cleavage reactions was significantly different in
      the mutant MRP1 proteins than in the wild type. Although the transported
      substrates (e.g. etoposide + oxidized glutathione) stimulated the formation of
      the posthydrolytic complex in the wild type, this reaction was inhibited in the
      signature mutants. Our study also revealed that a similar mutation in the ABC
      signature of either ABC unit resulted in the same effect. We suggest that the
      conserved glycine residues in both LSGGQ segments are part of the conformational
      network, which is responsible for the accelerated hydrolytic activity upon
      interaction of the protein with its transported substrates. This intramolecular
      communication between the substrate-binding site and the catalytic centers is
      assumed to be a general feature of the molecular mechanism of ABC transporters.

PMID- 15252018
TI  - Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition
      of activation and nuclear localization of nuclear factor kappa B.
AB  - Recent studies have implicated inhibitor of kappaB kinase (IKK) in mediating
      fatty acid (FA)-induced insulin resistance. How IKK causes these effects is
      unknown. The present study addressed the role of nuclear factor kappaB
      (NFkappaB), the distal target of IKK activity, in FA-induced insulin resistance
      in L6 myotubes, an in vitro skeletal muscle model. A 6-h exposure of myotubes to
      the saturated FA palmitate reduced insulin-stimulated glucose uptake by
      approximately 30%, phosphatidylinositol-3 kinase and protein kinase B
      phosphorylation by approximately 40%, and stimulated inhibitor of kappaBalpha
      degradation and the nuclear translocation of NFkappaB. On the other hand, the
      Omega-3 polyunsaturated FA linolenate neither induced insulin resistance nor
      promoted nuclear localization of NFkappaB. Supporting the hypothesis that IKK
      acts through NFkappaB to cause insulin resistance, the IKK inhibitors
      acetylsalicylate and parthenolide prevented FA-induced reductions in insulin
      stimulated glucose uptake and NFkappaB nuclear translocation. Most importantly,
      NFkappaB SN50, a cell-permeable peptide that inhibits NFkappaB nuclear
      translocation downstream of IKK, was sufficient to prevent palmitate-induced
      reductions in insulin-stimulated glucose uptake. Acetylsalicylate, but not
      NFkappaB SN50, prevented FA effects on phosphatidylinositol-3 kinase activity and
      protein kinase B phosphorylation. We conclude that FAs induce insulin resistance
      and activates NFkappaB in L6 cells. Furthermore, inhibition of NFkappaB
      activation, indirectly by preventing IKK activation or directly by inhibiting
      NFkappaB nuclear translocation, prevents the detrimental effects of palmitate on
      the metabolic actions of insulin in L6 myotubes.

PMID- 15252019
TI  - Mapping of a substrate binding site in the protein disulfide isomerase-related
      chaperone wind based on protein function and crystal structure.
AB  - The protein disulfide isomerase (PDI)-related protein Wind is essential in
      Drosophila melanogaster, and is required for correct targeting of Pipe, an
      essential Golgi transmembrane 2-O-sulfotransferase. Apart from a thioredoxin fold
      domain present in all PDI proteins, Wind also has a unique C-terminal D-domain
      found only in PDI-D proteins. Here, we show that Pipe processing requires dimeric
      Wind, which interacts directly with the soluble domain of Pipe in vitro, and we
      map an essential substrate binding site in Wind to the vicinity of an exposed
      cluster of tyrosines within the thioredoxin fold domain. In vitro, binding occurs
      to multiple sites within the Pipe polypeptide and shows specificity for two
      consecutive aromatic residues. A second site in Wind, formed by a cluster of
      residues within the D-domain, is likewise required for substrate processing. This
      domain, expressed separately, impairs Pipe processing by the full-length Wind
      protein, indicating competitive binding to substrate. Our data represent the most
      accurate map of a peptide binding site in a PDI-related protein available to date
      and directly show peptide specificity for a naturally occurring substrate.

PMID- 15252020
TI  - Two regions promote U11 small nuclear ribonucleoprotein particle binding to a
      retroviral splicing inhibitor element (negative regulator of splicing).
AB  - The Rous sarcoma virus (RSV) negative regulator of splicing (NRS) is an RNA
      element that represses splicing and promotes polyadenylation of viral RNA. The
      NRS acts as a pseudo 5' splice site (ss), and serine-arginine (SR) proteins,
      U1snRNP, and U6 small nuclear ribonucleoproteins (snRNPs) are implicated in its
      function. The NRS also efficiently binds U11 snRNP of the U12-dependent splicing
      pathway, which is interesting, because U11 binds only poorly to authentic
      substrates that lack a U12-type 3' splice site. It is of considerable interest to
      understand how the low abundance U11 snRNP binds the NRS so well. Here we show
      that U11 can bind the NRS as a mono-snRNP in vitro and that a G-rich element
      located downstream of the U11 site is required for efficient binding. Mutational
      analyses indicated that two of four G tracts in this region were important for
      optimal U11 binding and that the G-rich region did not function indirectly by
      promoting U1 snRNP binding to an overlapping site. Surprisingly, inactivation of
      U2 snRNP also decreased U11 binding to the NRS. The NRS harbors a branch point
      like/pyrimidine tract sequence (BP/Py) just upstream of the U1/U11 site that is
      characteristic of 3' splice sites. Deletion of this region decreased U2 and U11
      binding, and deletion of the G-rich region also reduced U2 binding. The G
      element, but not the BP/Py sequence, was also required for U11 binding to the NRS
      in vivo as assessed by minor class splicing from the NRS to a minor class 3'ss
      from the P120 gene. These results indicate that efficient U11 binding to the
      isolated NRS involves at least two elements in addition to the U11 consensus
      sequence and may have implications for U11 binding to authentic splicing
      substrates.

PMID- 15252021
TI  - Role of tyrosine phosphorylation in the regulation of cleavage secretion of
      angiotensin-converting enzyme.
AB  - Both germinal (gACE) and somatic (sACE) isozymes of angiotensin-converting enzyme
      (ACE) are type I ectoproteins whose enzymatically active ectodomains are cleaved
      and shed by a membrane-bound protease. Here, we report a role of protein tyrosine
      phosphorylation in regulating this process. Strong enhancements of ACE cleavage
      secretion was observed upon enhancing protein Tyr phosphorylation by treating
      gACE- or sACE-expressing cells with pervanadate, an inhibitor of protein Tyr
      phosphatases. Secreted gACE, cell-bound mature gACE and its precursors were all
      Tyr-phosphorylated, as was the endoplasmic reticulum protein, immunoglobulin
      heavy chain-binding protein, that co-immunoprecipitated with ACE. The enhancement
      of cleavage secretion by pervanadate did not require the presence of the
      cytoplasmic domain of ACE, and it was not accomplished by enhancing the rate of
      intracellular processing of the protein. The observed enhancement of cleavage
      secretion of ACE in pervanadate-treated cells was specifically blocked by an
      inhibitor of the p38 mitogen-activated protein (MAP) kinase but not by inhibitors
      of many other Ser/Thr and Tyr protein kinases, including a specific inhibitor of
      protein kinase C that, however, could block the enhancement of cleavage secretion
      elicited by phorbol ester. These results indicate that ACE Tyr phosphorylation,
      probably in the endoplasmic reticulum, enhances the rate of its cleavage
      secretion at the plasma membrane using a regulatory pathway that may involve p38
      MAP kinase.

PMID- 15252022
TI  - Gain of function mutation in the mineralocorticoid receptor of the Brown Norway
      rat.
AB  - The aim of this research was to identify the molecular bases of differences in
      sensitivity to corticosteroid hormones between Brown Norway and Fischer 344 rats.
      We previously showed an apparent insensitivity to adrenalectomy in Brown Norway
      rats. Based on our first hypothesis of a different activity/reactivity of the
      mineralocorticoid signaling pathway between the two rat strains, we sequenced
      Brown Norway and Fischer 344 mineralocorticoid receptor cDNA and identified a
      tyrosine to cysteine substitution (Y73C) in the N-terminal part of the Brown
      Norway mineralocorticoid receptor. As a first step, this substitution gave us a
      means to distinguish the Brown Norway allele from the Fischer 344 at the
      mineralocorticoid receptor locus in an F2 population. We showed a strong genetic
      linkage between the mineralocorticoid receptor genotype and sensitivity to
      adrenalectomy. A subsequent genome-wide linkage analysis confirmed the
      involvement of the mineralocorticoid receptor locus and implicated other loci,
      including one on chromosome 4, which collectively explain a large part of the
      strain differences in corticosteroid receptor responses. In vitro studies further
      revealed that the Y73C substitution induces greater transactivation of the
      mineralocorticoid receptor by aldosterone, and surprisingly by progesterone as
      well, which could substitute for aldosterone after adrenalectomy in Brown Norway
      rats. We challenged this hypothesis in vivo and showed that plasma progesterone
      is higher in Brown Norway male rats and partially compensates for aldosterone
      after adrenalectomy. This work illustrates the interest of a pluristrategic
      approach to explore the mineralocorticoid receptor signaling pathway and its
      implication in the regulation of hydroelectrolytic homeostasis and blood
      pressure.

PMID- 15252023
TI  - Identification of a low affinity mannose 6-phosphate-binding site in domain 5 of
      the cation-independent mannose 6-phosphate receptor.
AB  - The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) and the 46
      kDa cation-dependent MPR (CD-MPR) are type I integral membrane glycoproteins that
      play a critical role in the intracellular delivery of newly synthesized mannose 6
      phosphate (Man-6-P)-containing acid hydrolases to the lysosome. The
      extracytoplasmic region of the CI-MPR contains 15 contiguous domains, and the two
      high affinity ( approximately 1 nm) Man-6-P-binding sites have been mapped to
      domains 1-3 and 9, with essential residues localized to domains 3 and 9. Domain 5
      of the CI-MPR exhibits significant sequence homology to domains 3 and 9 as well
      as to the CD-MPR. A structure-based sequence alignment was performed that
      predicts that domain 5 contains the four conserved key residues (Gln, Arg, Glu,
      and Tyr) identified as essential for carbohydrate recognition by the CD-MPR and
      domains 3 and 9 of the CI-MPR, but lacks two cysteine residues predicted to form
      a disulfide bond within the binding pocket. To determine whether domain 5 harbors
      a carbohydrate-binding site, a construct that encodes domain 5 alone (Dom5His)
      was expressed in Pichia pastoris. Microarray analysis using 30 different
      oligosaccharides demonstrated that Dom5His bound specifically to a Man-6-P
      containing oligosaccharide (pentamannosyl 6-phosphate). Frontal affinity
      chromatography showed that the affinity of Dom5His for Man-6-P was approximately
      300-fold lower (K(i) = 5.3 mm) than that observed for domains 1-3 and 9. The
      interaction affinity for the lysosomal enzyme beta-glucuronidase was also much
      lower (K(d) = 54 microm) as determined by surface plasmon resonance analysis.
      Taken together, these results demonstrate that the CI-MPR contains a third Man-6
      P recognition site that is located in domain 5 and that exhibits lower affinity
      than the carbohydrate-binding sites present in domains 1-3 and 9.

PMID- 15252024
TI  - Domain architecture and activity of human Pex19p, a chaperone-like protein for
      intracellular trafficking of peroxisomal membrane proteins.
AB  - Pex19p is a peroxin involved in peroxisomal membrane biogenesis and probably
      functions as a chaperone and/or soluble receptor specific for cargo peroxisomal
      membrane proteins (PMPs). To elucidate the functional constituents of Pex19p in
      terms of the protein structure, we investigated its domain architecture and
      binding affinity toward various PMPs and peroxins. The human Pex19p cDNA was
      overexpressed in Escherichia coli, and a highly purified sample of the Pex19p
      protein was prepared. When PMP22 was synthesized by cell-free translation in the
      presence of Pex19p, the PMP22 bound to Pex19p was soluble, whereas PMP22 alone
      was insoluble. This observation shows that Pex19p plays a role in capturing PMP
      and maintaining its solubility. In a similar manner, Pex19p was bound to PMP70
      and Pex16p as well as the Pex3p soluble fragment. Limited proteolysis analyses
      revealed that Pex19p consists of the C-terminal core domain flanking the flexible
      N-terminal region. Separation of Pex19p into its N- and C-terminal halves
      abolished interactions with PMP22, PMP70, and Pex16p. In contrast, the flexible N
      terminal half of Pex19p was bound to the Pex3p soluble fragment, suggesting that
      the binding mode of Pex3p toward Pex19p differs from that of other PMPs. This
      idea is supported by our detection of the Pex19p-Pex3p-PMP22 ternary complex.

PMID- 15252025
TI  - A theoretical model of type I collagen proteolysis by matrix metalloproteinase
      (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of
      metalloproteinase 2.
AB  - One well documented family of enzymes responsible for the proteolytic processes
      that occur in the extracellular matrix is the soluble and membrane-associated
      matrix metalloproteinases. Here we present the first theoretical model of the
      biochemical network describing the proteolysis of collagen I by matrix
      metalloproteinases 2 (MMP2) and membrane type 1 matrix metalloproteinases (MT1
      MMP) in the presence of the tissue inhibitor of metalloproteinases 2 (TIMP2) in a
      bulk, cell-free, well stirred environment. The model can serve as a tool for
      describing quantitatively the activation of the MMP2 proenzyme (pro-MMP2), the
      ectodomain shedding of MT1-MMP, and the collagenolysis arising from both of the
      enzymes. We show that pro-MMP2 activation, a process that involves a trimer
      formation of the proenzyme with TIMP2 and MT1-MMP, is suppressed at high
      inhibitor levels and paradoxically attains maximum only at intermediate TIMP2
      concentrations. We also calculate the conditions for which pro-MMP2 activation is
      maximal. Furthermore we demonstrate that the ectodomain shedding of MT1-MMP can
      serve as a mechanism controlling the MT1-MMP availability and therefore the pro
      MMP2 activation. Finally the proteolytic synergism of MMP2 and MT1-MMP is
      introduced and described quantitatively. The model provides us a tool to
      determine the conditions under which the synergism is optimized. Our approach is
      the first step toward a more complete description of the proteolytic processes
      that occur in the extracellular matrix and include a wider spectrum of enzymes
      and substrates as well as naturally occurring or artificial inhibitors.

PMID- 15252027
TI  - Effect of insulin on caveolin-enriched membrane domains in rat liver.
AB  - Compartmentalization of signaling molecules may explain, at least in part, how
      insulin or growth factors achieve specificity. Caveolae/rafts are specialized
      lipid compartments that have been implicated in insulin signaling. In the present
      study, we investigated the role of caveolin-enriched membrane domains (CMD) in
      mediating insulin signaling in rat liver. We report the existence of at least two
      different populations of CMD in rat liver plasma membranes (PM). One population
      is soluble in Triton X-100 and seems to be constitutively associated with
      cytoskeletal elements. The other population of CMD is located in a membrane
      compartment insoluble in Triton X-100 with light buoyant density and is hence
      designated CMD/rafts. We found evidence of rapid actin reorganization in rat
      liver PM in response to insulin, along with the association of CMD/rafts and
      insulin signaling molecules with a cell fraction enriched in cytoskeletal
      elements. The presence of CMD in liver parenchyma cells was confirmed by the
      presence of caveolin-1 in primary rat hepatocyte cultures. Cholesterol depletion,
      effected by incubating hepatocytes with 2 mm methyl-beta-cyclodextrin, did not
      permeabilize the cells or interfere with clathrin-dependent internalization.
      However, at this concentration, methyl-beta-cyclodextrin perturbed CMD of
      hepatocyte PM and inhibited insulin-induced Akt activation and glycogen synthesis
      but did not affect insulin-induced insulin receptor kinase tyrosine
      phosphorylation. These events, together with the presence of a functional insulin
      receptor in CMD of rat liver PM, suggest that insulin signaling is influenced by
      the interaction of caveolae with cytoskeletal elements in liver.

PMID- 15252026
TI  - Male mice that do not express group VIA phospholipase A2 produce spermatozoa with
      impaired motility and have greatly reduced fertility.
AB  - The Group VIA Phospholipase A(2) (iPLA(2)beta) is the first recognized cytosolic
      Ca(2+)-independent PLA(2) and has been proposed to participate in arachidonic
      acid (20:4) incorporation into glycerophosphocholine lipids, cell proliferation,
      exocytosis, apoptosis, and other processes. To study iPLA(2)beta functions, we
      disrupted its gene by homologous recombination to generate mice that do not
      express iPLA(2)beta. Heterozygous iPLA(2)beta(+/-) breeding pairs yield a
      Mendelian 1:2:1 ratio of iPLA(2)beta(+/+), iPLA(2)beta(+/-), and iPLA(2)beta(-/-)
      pups and a 1:1 male:female gender distribution of iPLA(2)beta(-/-) pups. Several
      tissues of wild-type mice express iPLA(2)beta mRNA, immunoreactive protein, and
      activity, and testes express the highest levels. Testes or other tissues of
      iPLA(2)beta(-/-) mice express no iPLA(2)beta mRNA or protein, but iPLA(2)beta(-/
      ) testes are not deficient in 20:4-containing glycerophosphocholine lipids,
      indicating that iPLA(2)beta does not play an obligatory role in formation of such
      lipids in that tissue. Spermatozoa from iPLA(2)beta(-/-) mice have reduced
      motility and impaired ability to fertilize mouse oocytes in vitro and in vivo,
      and inhibiting iPLA(2)beta with a bromoenol lactone suicide substrate reduces
      motility of wild-type spermatozoa in a time- and concentration-dependent manner.
      Mating iPLA(2)beta(-/-) male mice with iPLA(2)beta(+/+), iPLA(2)beta(+/-), or
      iPLA(2)beta(-/-) female mice yields only about 7% of the number of pups produced
      by mating pairs with an iPLA(2)beta(+/+) or iPLA(2)beta(+/-) male, but
      iPLA(2)beta(-/-) female mice have nearly normal fertility. These findings
      indicate that iPLA(2)beta plays an important functional role in spermatozoa,
      suggest a target for developing male contraceptive drugs, and complement reports
      that disruption of the Group IVA PLA(2) (cPLA(2)alpha) gene impairs female
      reproductive ability.

PMID- 15252028
TI  - The Ca2+ homeostasis defects in a pgm2Delta strain of Saccharomyces cerevisiae
      are caused by excessive vacuolar Ca2+ uptake mediated by the Ca2+-ATPase Pmc1p.
AB  - Loss of the major isoform of phosphoglucomutase (PGM) causes an accumulation of
      glucose 1-phosphate when yeast cells are grown with galactose as the carbon and
      energy source. Remarkably, the pgm2Delta strain also exhibits a severe imbalance
      in intracellular Ca(2+) homeostasis when grown under these conditions. In the
      present study, we examined how the pgm2Delta mutation alters yeast Ca(2+)
      homeostasis in greater detail. We found that a shift from glucose to galactose as
      the carbon source resulted in a 2-fold increase in the rate of cellular Ca(2+)
      uptake in wild-type cells, whereas Ca(2+) uptake increased 8-fold in the
      pgm2Delta mutant. Disruption of the PMC1 gene, which encodes the vacuolar Ca(2+)
      ATPase Pmc1p, suppressed the Ca(2+)-related phenotypes observed in the pgm2Delta
      strain. This suggests that excessive vacuolar Ca(2+) uptake is tightly coupled to
      these defects in Ca(2+) homeostasis. An in vitro assay designed to measure Ca(2+)
      sequestration into intracellular compartments confirmed that the pgm2Delta mutant
      contained a higher level of Pmc1p-dependent Ca(2+) transport activity than the
      wild-type strain. We found that this increased rate of vacuolar Ca(2+) uptake
      also coincided with a large induction of the unfolded protein response in the
      pgm2Delta mutant, suggesting that Ca(2+) uptake into the endoplasmic reticulum
      compartment was reduced. These results indicate that the excessive Ca(2+) uptake
      and accumulation previously shown to be associated with the pgm2Delta mutation
      are due to a severe imbalance in the distribution of cellular Ca(2+) into
      different intracellular compartments.

PMID- 15252029
TI  - FGF18 represses noggin expression and is induced by calcineurin.
AB  - Fibroblast growth factors (FGFs) and bone morphogenetic proteins strongly
      regulate chondrogenesis and chondrocyte gene expression. The interactions of the
      signaling pathways initiated by these factors are central to the control of
      chondrocyte differentiation. Here we show that calcium-dependent signals induce
      expression of FGF18, an essential regulator of bone and cartilage
      differentiation. The induction of FGF18 expression required the calcium-dependent
      phosphatase, calcineurin. The activated forms of calcineurin or the calcineurin
      dependent transcription factor, NFAT4 (nuclear factor of activated T-cell 4),
      induced FGF18 expression. FGF18 or a constitutive active FGF receptor suppressed
      noggin gene induction and thereby increased chondrocyte gene expression and
      chondrogenesis by facilitating bone morphogenetic protein-dependent signals.
      These findings reinforce the interdependence of bone morphogenetic protein and
      FGF signaling and provide a rational explanation for abnormal bone development
      occurring in humans or mice with constitutively active FGF receptors.

PMID- 15252030
TI  - Characterization of two distinct dual specificity phosphatases encoded in
      alternative open reading frames of a single gene located on human chromosome
      10q22.2.
AB  - Dual specificity phosphatases (DSPs) are members of the protein-tyrosine
      phosphatase superfamily that dephosphorylate both phosphotyrosine and
      phosphoserine/threonine residues in vitro. Many DSPs have been found to play
      important roles in various aspects of cellular function and to be involved in
      human disease. We have identified a gene located on human chromosome 10q22.2,
      which utilizes alternative open reading frames (ORFs) to encode the following two
      distinct DSPs: the previously described testis and skeletal muscle-specific dual
      specificity phosphatase (TMDP) and a novel DSP, muscle-restricted dual
      specificity phosphatase (MDSP). Use of alternative ORFs encoding distinct
      proteins from a single gene is extremely rare in eukaryotes, and in all
      previously reported cases the two proteins produced from one gene are unrelated.
      To our knowledge this is the first example of a gene from which two distinct
      proteins of the same family are expressed using alternative ORFs. Here we provide
      evidence that both MDSP and TMDP proteins are expressed in vivo and are
      restricted to specific tissues, skeletal muscle and testis, respectively. Most
      interestingly, the protein expression profiles of both MDSP and TMDP during mouse
      postnatal development are strikingly similar. MDSP is expressed at very low
      levels in myotubes and early postnatal muscle. TMDP is not detectable in testis
      lysate in the first 3 weeks of life. The expression of both MDSP and TMDP
      proteins was markedly increased at approximately the 3rd week after birth and
      continued to increase gradually into adulthood, implying that the physiological
      functions of both DSPs are specific to the mature/late-developing organs. The
      conserved gene structure and the similarity in postnatal expression profile of
      these two proteins suggest biological significance of the unusual gene
      arrangement.

PMID- 15252031
TI  - Mutational analysis and characterization of nocardicin C-9' epimerase.
AB  - The biosynthetic gene cluster for the nocardicin A producer Nocardia uniformis
      subsp. tsuyamanensis ATCC 21806 was recently identified. Nocardicin A is the most
      potent of a series of monocyclic beta-lactam antibiotics produced by this
      organism. Its activity has been attributed to a syn-configured oxime moiety and a
      d-homoseryl side chain attached through an unusual ether linkage to the core
      nocardicin framework. Notably present in the nocardicin biosynthetic gene cluster
      is nocJ, encoding a protein with sequence similarity to the pyridoxal 5'
      phosphate (PLP)-dependent 1-aminocyclopropane-1-carboxylic acid deaminases.
      Insertional mutagenesis of nocJ abolished nocardicin A production, while the l
      homoseryl isomer, isonocardicin A, was still observed. Expression of the
      disrupted nocJ gene in trans was sufficient to restore production of nocardicin A
      in the disruption mutant. Heterologous expression, purification, and in vitro
      characterization of NocJ by UV spectroscopy, cofactor reduction, chiral HPLC
      analysis of the products and their exchange behavior in deuterium oxide led to
      confirmation of its role as the PLP-dependent nocardicin C-9' epimerase
      responsible for interconversion of the nocardicin homoseryl side chain in both
      nocardicin A with isonocardicin A, and nocardicin C with isonocardicin C. NocJ is
      the first member of a new class of beta-lactam aminoacyl side chain epimerases,
      the first two classes being the evolutionarily distinct prokaryotic PLP-dependent
      isopenicillin N epimerase and the fungal isopenicillin N epimerase two protein
      system.

PMID- 15252032
TI  - An evolutionary conserved pathway of nuclear factor-kappaB activation involving
      caspase-mediated cleavage and N-end rule pathway-mediated degradation of
      IkappaBalpha.
AB  - The Drosophila nuclear factor-kappaB (NF-kappaB)-like transcription factor Relish
      is activated by an endoproteolytic cleavage step mediated by the Drosophila
      caspase Dredd. We have examined the contribution of the caspase cascade to NF
      kappaB activation via TRAIL, a mammalian tumor necrosis factor family ligand that
      is a potent activator of caspases. Our results demonstrate that TRAIL activates
      NF-kappaB in two phases as follows: an early caspase independent phase and a late
      caspase dependent phase. The late phase of the TRAIL-induced NF-kappaB is
      critically dependent on caspase 8 and can be blocked by pharmacological and
      genetic inhibitors of caspase 8 activation, such as benzyloxycarbonyl-VAD
      fluoromethyl ketone, benzyloxycarbonyl-IETD-fluoromethyl ketone, and small
      interfering RNA targeting caspase 8 and FADD. Whereas caspase 3 is required for
      TRAIL-induced apoptosis, it is not involved in TRAIL-induced NF-kappaB
      activation. The late phase of TRAIL-induced NF-kappaB activation involves caspase
      mediated cleavage of IkappaBalpha between Asp(31) and Ser(32) residues to
      generate an N-terminal truncated fragment that is degraded by the proteasome via
      the N-end rule pathway. Our results demonstrate that caspases play an
      evolutionarily conserved role as regulated entry points to the N-end rule pathway
      and in NF-kappaB activation in mammalian cells.

PMID- 15252033
TI  - The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity
      pocket.
AB  - The thrombin mutant W215A/E217A features a drastically impaired catalytic
      activity toward chromogenic and natural substrates but efficiently activates the
      anticoagulant protein C in the presence of thrombomodulin. As the remarkable
      anticoagulant properties of this mutant continue to be unraveled in preclinical
      studies, we solved the x-ray crystal structures of its free form and its complex
      with the active site inhibitor H-d-Phe-Pro-Arg-CH(2)Cl (PPACK). The PPACK-bound
      structure of W215A/E217A is identical to the structure of the PPACK-bound slow
      form of thrombin. On the other hand, the structure of the free form reveals a
      collapse of the 215-217 strand that crushes the primary specificity pocket. The
      collapse results from abrogation of the stacking interaction between Phe-227 and
      Trp-215 and the polar interactions of Glu-217 with Thr-172 and Lys-224. Other
      notable changes are a rotation of the carboxylate group of Asp-189, breakage of
      the H-bond between the catalytic residues Ser-195 and His-57, breakage of the ion
      pair between Asp-222 and Arg-187, and significant disorder in the 186- and 220
      loops that define the Na(+) site. These findings explain the impaired catalytic
      activity of W215A/E217A and demonstrate that the analysis of the molecular basis
      of substrate recognition by thrombin and other proteases requires crystallization
      of both the free and bound forms of the enzyme.

PMID- 15252034
TI  - The atomic resolution crystal structure of atratoxin determined by single
      wavelength anomalous diffraction phasing.
AB  - By using single wavelength anomalous diffraction phasing based on the anomalous
      signal from copper atoms, the crystal structure of atratoxin was determined at
      the resolution of 1.5 A and was refined to an ultrahigh resolution of 0.87 A. The
      ultrahigh resolution electron density maps allowed the modeling of 38 amino acid
      residues in alternate conformations and the location of 322 of 870 possible
      hydrogen atoms. To get accurate information at the atomic level, atratoxin-b (an
      analog of atratoxin with reduced toxicity) was also refined to an atomic
      resolution of 0.92 A. By the sequence and structural comparison of these two
      atratoxins, Arg(33) and Arg(36) were identified to be critical to their varied
      toxicity. The effect of copper ions on the distribution of hydrogen atoms in
      atratoxin was discussed, and the interactions between copper ions and protein
      residues were analyzed based on a statistical method, revealing a novel
      pentahedral copper-binding motif.

PMID- 15252035
TI  - The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks
      osteoclastogenesis and bone erosion in inflammatory arthritis.
AB  - Activation of NF-kappaB leads to expression of ample genes that regulate
      inflammatory and osteoclastogenic responses. The process is facilitated by
      induction of IkappaB kinase (IKK) complex that phosphorylates IkappaB and leads
      to its dissociation from the NF-kappaB complex, thus permitting activation of NF
      kappaB. The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory
      kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity
      through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, termed
      NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been
      shown to block association of NEMO with the IKK complex and inhibit activation of
      NF-kappaB. Given the pivotal role of cytokine-induced NF-kappaB in
      osteoclastogenesis and inflammatory bone loss, we deduced that cell-permeable TAT
      NBD peptide may hinder osteoclastogenesis and bone erosion in inflammatory
      arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks
      IKK activation and reduces cytokine-induced promoter and DNA binding activities
      of NF-kappaB and inhibits cytokine-induced osteoclast formation by osteoclast
      precursors. Consistent with the key role of NF-kappaB in osteoinflammatory
      responses in vivo, wild type TAT-NBD administered into mice prior to induction of
      inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits
      focal bone erosion, and ameliorates inflammatory responses in the joints of
      arthritic mice. The mutant NBD peptide fails to exert these functions. These
      results provide strong evidence that IKKs are potent regulators of cytokine
      induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade
      of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory
      osteolysis.

PMID- 15252036
TI  - Gfi1:green fluorescent protein knock-in mutant reveals differential expression
      and autoregulation of the growth factor independence 1 (Gfi1) gene during
      lymphocyte development.
AB  - The Gfi1 gene encodes a 55-kDa transcriptional repressor protein with important
      functions in T-cell development, in granulopoiesis, and in the regulation of the
      innate immune response. To follow expression of the Gfi1 gene during the
      differentiation of specific immune cells, we have generated a mouse mutant in
      which the Gfi1 coding region is replaced by the gene for the green fluorescent
      protein (GFP). We found that Gfi1 gene expression is highest in early B-cell
      subpopulation and differentially expressed during T-cell development with peak
      levels at stages where pre-TCR or positive/negative selection takes place. Gfi1
      is absent in mature B-cells, whereas in peripheral T-cells Gfi1 gene expression
      is low but rises significantly upon T-cell receptor triggering and decreases
      again in T-memory cells. Constitutive expression of an lck promoter-driven Gfi1
      transgene led to transcriptional silencing of the Gfi1:GFP allele in T-cells.
      Because Gfi1 was found to occupy genomic sites of its own promoter in thymocytes
      and was able to repress its own transcription in vitro we propose that
      transcription of the Gfi1 gene is regulated through an autoregulatory feedback
      loop.

PMID- 15252037
TI  - Overlapping binding sites in protein phosphatase 2A for association with
      regulatory A and alpha-4 (mTap42) subunits.
AB  - Diverse functions of protein Ser/Thr phosphatases depend on the distribution of
      the catalytic subunits among multiple regulatory subunits. In cells protein
      phosphatase 2A catalytic subunit (PP2Ac) mostly binds to a scaffold subunit (A
      subunit or PR65); however, PP2Ac alternatively binds to alpha-4, a subunit
      related to yeast Tap42 protein, which also associates with phosphatases PP4 or
      PP6. We mapped alpha-4 binding to PP2Ac to the helical domain, residues 19-165.
      We mutated selected residues and transiently expressed epitope-tagged PP2Ac to
      assay for association with A and alpha-4 subunits by co-precipitation. The
      disabling H118N mutation at the active site or the presence of the active site
      inhibitor microcystin-LR did not interfere with binding of PP2Ac to either the A
      subunit or alpha-4, showing that these are allosteric regulators. Positively
      charged side chains Lys(41), Arg(49), and Lys(74) on the back surface of PP2Ac
      are unique to PP2Ac, compared with phosphatases PP4, PP6, and PP1. Substitution
      of one, two, or three of these residues with Ala produced a progressive loss of
      binding to the A subunit, with a corresponding increase in binding to alpha-4.
      Conversely, mutation of Glu(42) in PP2Ac essentially eliminated PP2Ac binding to
      alpha-4, with an increase in binding to the A subunit. Reciprocal changes in
      binding because of mutations indicate competitive distribution of PP2Ac between
      these regulatory subunits and demonstrate that the mutated catalytic subunits
      retained a native conformation. Furthermore, neither the Lys(41)-Arg(49)-Lys(74)
      nor Glu(42) mutations affected the phosphatase-specific activity or binding to
      microcystin-agarose. Binding of PP2Ac to microcystin and to alpha-4 increased
      with temperature, consistent with an activation energy barrier for these
      interactions. Our results reveal that the A subunit and alpha-4 (mTap42) require
      charged residues in separate but overlapping surface regions to associate with
      the back side of PP2Ac and modulate phosphatase activity.

PMID- 15252038
TI  - Role of group VIA calcium-independent phospholipase A2 in arachidonic acid
      release, phospholipid fatty acid incorporation, and apoptosis in U937 cells
      responding to hydrogen peroxide.
AB  - Group VIA calcium-independent phospholipase A2 (iPLA2) has been shown to play a
      major role in regulating basal phospholipid deacylation reactions in certain cell
      types. More recently, roles for this enzyme have also been suggested in the
      destruction of membrane phospholipid during apoptosis and after oxidant injury.
      Proposed iPLA2 roles have rested heavily on the use of bromoenol lactone as an
      iPLA2-specific inhibitor, but this compound actually inhibits other enzymes and
      lipid pathways unrelated to PLA2, which makes it difficult to define the
      contribution of iPLA2 to specific functions. In previous work, we pioneered the
      use of antisense technology to decrease cellular iPLA2 activity as an alternative
      approach to study iPLA2 functions. In the present study, we followed the opposite
      strategy and prepared U937 cells that exhibited enhanced iPLA activity by stably
      expressing a plasmid containing iPLA2 cDNA. Compared with control cells, the
      iPLA2 -overexpressing U937 cells showed elevated responses to hydrogen peroxide
      with regard to both arachidonic acid mobilization and incorporation of the fatty
      acid into phospholipids, thus providing additional evidence for the key role that
      iPLA2 plays in these events. Long-term exposure of the cells to hydrogen peroxide
      resulted in cell death by apoptosis, and this process was accelerated in the
      iPLA2-overexpressing cells. Increased phospholipid hydrolysis and fatty acid
      release also occurred in these cells. Unexpectedly, however, abrogation of U937
      cell iPLA2 activity by either methyl arachidonyl fluorophosphonate or an
      antisense oligonucleotide did not delay or decrease the extent of apoptosis
      induced by hydrogen peroxide. These results indicate that, although iPLA2
      mediated phospholipid hydrolysis occurs during apoptosis, iPLA2 may actually be
      dispensable for the apoptotic process to occur. Thus, beyond a mere destructive
      role, iPLA2 may play other roles during apoptosis.

PMID- 15252039
TI  - Induction of ID2 expression by hypoxia-inducible factor-1: a role in
      dedifferentiation of hypoxic neuroblastoma cells.
AB  - ID (inhibitor of differentiation/DNA binding) proteins, frequently deregulated in
      advanced human malignancies, can participate in multiple fundamental traits of
      cancer, such as block of differentiation, increased proliferation, tissue
      invasiveness, and angiogenesis. We have previously demonstrated that hypoxia
      decreases expression of neuronal marker genes in neuroblastoma, but induces genes
      expressed in the neural crest, such as ID2. Because of its involvement in normal
      neural crest development and its ability to inhibit proneuronal bHLH proteins,
      the hypoxic induction of ID2 was of particular interest. Here we report fast
      induction kinetics of ID2 expression in hypoxic neuroblastoma cells. The up
      regulation of ID2 was abolished by addition of actinomycin D, implicating a
      hypoxia-driven transcriptional mechanism. Analyzing the ID2 promoter revealed
      several potential binding sites for hypoxia-inducible factors. Subsequent
      electrophoretic mobility shift and chromatin immunoprecipitation assays
      demonstrated two functional HIF-1 binding sites within ID2 gene regulatory
      sequences located at -725 and -1893 relative to the transcriptional initiation
      point. In transfection assays, DNA constructs of the ID2 promoter, including the
      functional HIF-1 binding sites, induced luciferase reporter activity in a HIF-1
      specific manner. These observations demonstrate that ID2 is actively engaged by
      hypoxia and represents a novel HIF-1 target. Hypoxia-induced ID2 expression could
      play a significant role in the previously observed dedifferentiation of hypoxic
      neuroblastoma cells, which in a clinical setting could lead to less mature and
      more aggressive tumors.

PMID- 15252040
TI  - Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency.
AB  - Foxa1 is a member of the winged helix family of transcription factors and is
      expressed in the collecting ducts of the kidney. We investigated its potential
      contribution to renal physiology in Foxa1-deficient mice on a defined genetic
      background. Foxa1(-/-) mice are dehydrated and exhibit electrolyte imbalance as
      evidenced by elevated hematocrit and plasma urea levels, hypernatremia, and
      hyperkalemia. This phenotype is the consequence of decreased urine osmolality
      secondary to renal vasopressin resistance. Mutations of the human genes encoding
      the vasopressin 2 receptor and aquaporin 2 cause nephrogenic diabetes insipidus;
      however, expression of these genes is maintained or increased, respectively, in
      Foxa1(-/-) mice. Likewise, expression of the genes encoding the Na-K-2Cl
      cotransporter (NKCC2), the potassium channel ROMK, the chloride channel CLCNKB,
      barttin (BSND), and the calcium-sensing receptor (CASR), each of which is
      important in sodium reabsorption in the loop of Henle, is maintained or even
      increased in Foxa1-deficient mice. Thus, we have shown that Foxa1(-/-) mice
      represent a new model of nephrogenic diabetes insipidus with unique molecular
      etiology, and we have identified the first transcription factor whose mutation
      leads to a defect in renal water homeostasis in vivo.

PMID- 15252041
TI  - Genetic deletion of glycogen synthase kinase-3beta abrogates activation of
      IkappaBalpha kinase, JNK, Akt, and p44/p42 MAPK but potentiates apoptosis induced
      by tumor necrosis factor.
AB  - Glycogen synthase kinase (GSK)-3beta is a constitutively active, proline-directed
      serine/threonine kinase that controls growth modulation and tumorigenesis through
      multiple intracellular signaling pathways. How GSK-3beta regulates signaling
      pathways induced by cytokines such as tumor necrosis factor (TNF) is poorly
      understood. In this study, we used fibroblasts derived from GSK-3beta gene
      deleted mice to understand the role of this kinase in TNF signaling. TNF induced
      NF-kappaB activation as measured by DNA binding in wild-type mouse embryonic
      fibroblasts, but deletion of GSK-3beta abolished this activation. This inhibition
      was due to suppression of IkappaBalpha kinase activation and IkappaBalpha
      phosphorylation, ubiquitination, and degradation. TNF-induced NF-kappaB reporter
      gene transcription was also suppressed in GSK-3beta gene-deleted cells. NF-kappaB
      activation induced by lipopolysaccharide, interleukin-1beta, or cigarette smoke
      condensate was completely suppressed in GSK-3beta(-/-) cells. Deletion of GSK
      3beta also abolished TNF-induced c-Jun N-terminal kinase and p44/p42 mitogen
      activated kinase activation. Most surprisingly, TNF-induced Akt activation also
      required the presence of GSK-3beta. TNF induced expression of the NF-kappaB
      regulated gene products cyclin D1, COX-2, MMP-9, survivin, IAP 1, IAP 2, Bcl
      x(L), Bfl-1/A1, TRAF1, and FLIP in wild-type mouse embryonic fibroblasts but not
      in GSK-3beta(-/-) cells, and this correlated with potentiation of TNF-induced
      apoptosis as indicated by cell viability, annexin V staining, and caspase
      activation. Overall, our results indicate that GSK-3beta plays a critical role in
      TNF signaling and in the signaling of other inflammatory stimuli and that its
      suppression can be exploited as a potential target to inhibit angiogenesis,
      proliferation, and survival of tumor cells.

PMID- 15252043
TI  - Properties of the PriA helicase domain and its role in binding PriA to specific
      DNA structures.
AB  - Primosome assembly protein PriA functions in the assembly of the replisome at
      forked DNA structures. Whereas its N-terminal DNA binding domain (DBD) binds
      independently to DNA, the affinity of DBD protein for forked structures is
      relatively weak. Although the PriA helicase domain (HD) is required for high
      affinity fork binding, HD protein had very low affinity for DNA. It had only low
      levels of ATPase activity, and it hydrolyzed ATP when DNA was absent whereas PriA
      did not. HD catalyzed unwinding of a minimal substrate composed of a duplex with
      a 3' single-stranded tail. Single-strand binding protein (SSB) bound to the tail
      of this substrate inhibited this reaction by full-length PriA but enhanced the
      reaction by HD. SSB stabilized binding of PriA but not of DBD or HD to duplexes
      with a 5' or 3' single-stranded tail. On forked substrates SSB enhanced helicase
      action on the lagging-strand arm by PriA but not by HD. The results indicate that
      synergy of the DBD and HD allows stable binding at the interface between duplex
      and single-stranded DNA bound by SSB. This mode of binding may be analogous to
      fork binding, which orients the helicase to act on the lagging-strand side of the
      fork.

PMID- 15252042
TI  - Uncoupling of photoreceptor peripherin/rds fusogenic activity from biosynthesis,
      subunit assembly, and targeting: a potential mechanism for pathogenic effects.
AB  - Inherited defects in the RDS gene cause a multiplicity of progressive retinal
      diseases in humans. The gene product, peripherin/rds (P/rds), is a member of the
      tetraspanin protein family required for normal vertebrate photoreceptor outer
      segment (OS) architecture. Although its molecular function remains uncertain,
      P/rds has been suggested to catalyze membrane fusion events required for the OS
      renewal process. This study investigates the importance of two charged residues
      within a predicted C-terminal helical region for protein biosynthesis,
      localization, and interaction with model membranes. Targeted mutagenesis was
      utilized to neutralize charges at Glu(321) and Lys(324) individually and in
      combination to generate three mutant variants. Studies were conducted on variants
      expressed as 1) full-length P/rds in COS-1 cells, 2) glutathione S-transferase
      fusion proteins in Escherichia coli, and 3) membrane-associated green fluorescent
      protein fusion proteins in transgenic Xenopus laevis. None of the mutations
      affected biosynthesis of full-length P/rds in COS-1 cells as assessed by Western
      blotting, sedimentation velocity, and immunofluorescence microscopy. Although all
      mutations reside within a recently identified localization signal, none altered
      the ability of this region to direct OS targeting in transgenic X. laevis
      retinas. In contrast, individual or simultaneous neutralization of the charged
      amino acids Glu(321) and Lys(324) abolished the ability of the C-terminal domain
      to promote model membrane fusion as assayed by lipid mixing. These results
      demonstrate that, although overlapping, C-terminal determinants responsible for
      OS targeting and fusogenicity are separable and that fusogenic activity has been
      uncoupled from other protein properties. The observation that subunit assembly
      and OS targeting can both proceed normally in the absence of fusogenic activity
      suggests that properly assembled and targeted yet functionally altered proteins
      could potentially generate pathogenic effects within the vertebrate
      photoreceptor.

PMID- 15252044
TI  - Trafficking defects of a novel autosomal recessive distal renal tubular acidosis
      mutant (S773P) of the human kidney anion exchanger (kAE1).
AB  - Autosomal dominant and recessive distal renal tubular acidosis (dRTA) can be
      caused by mutations in the anion exchanger 1 (AE1 or SLC4A1) gene, which encodes
      the erythroid chloride/bicarbonate anion exchanger membrane glycoprotein (eAE1)
      and a truncated kidney isoform (kAE1). The biosynthesis and trafficking of kAE1
      containing a novel recessive missense dRTA mutation (kAE1 S773P) was studied in
      transiently transfected HEK-293 cells, expressing the mutant alone or in
      combination with wild-type kAE1 or another recessive mutant, kAE1 G701D. The kAE1
      S773P mutant was expressed at a three times lower level than wild-type, had a 2
      fold decrease in its half-life, and was targeted for degradation by the
      proteasome. It could not be detected at the plasma membrane in human embryonic
      kidney cells and showed predominant endoplasmic reticulum immunolocalization in
      both human embryonic kidney and LLC-PK1 cells. The oligosaccharide on a kAE1
      S773P N-glycosylation mutant (N555) was not processed to the complex form
      indicating impaired exit from the endoplasmic reticulum. The kAE1 S773P mutant
      showed decreased binding to an inhibitor affinity resin and increased sensitivity
      to proteases, suggesting that it was not properly folded. The other recessive
      dRTA mutant, kAE1 G701D, also exhibited defective trafficking to the plasma
      membrane. The recessive kAE1 mutants formed dimers like wild-type AE1 and could
      hetero-oligomerize with wild-type kAE1 or with each other. Hetero-oligomers of
      wild-type kAE1 with recessive kAE1 S773P or G701D, in contrast to the dominant
      kAE1 R589H mutant, were delivered to the plasma membrane.

PMID- 15252045
TI  - Dual action of antimonial drugs on thiol redox metabolism in the human pathogen
      Leishmania donovani.
AB  - Despite extensive use of antimonial compounds in the treatment of leishmaniasis,
      their mode of action remains uncertain. Here we show that trivalent antimony
      (Sb(III)) interferes with trypanothione metabolism in drug-sensitive Leishmania
      parasites by two inherently distinct mechanisms. First, Sb(III) decreases thiol
      buffering capacity by inducing rapid efflux of intracellular trypanothione and
      glutathione in approximately equimolar amounts. Second, Sb(III) inhibits
      trypanothione reductase in intact cells resulting in accumulation of the
      disulfide forms of trypanothione and glutathione. These two mechanisms combine to
      profoundly compromise the thiol redox potential in both amastigote and
      promastigote stages of the life cycle. Furthermore, we demonstrate that sodium
      stibogluconate, a pentavalent antimonial used clinically for the treatment for
      leishmaniasis, induces similar effects on thiol redox metabolism in axenically
      cultured amastigotes. These observations suggest ways in which current antimony
      therapies could be improved, overcoming the growing problem of antimony
      resistance.

PMID- 15252046
TI  - MuLK, a eukaryotic multi-substrate lipid kinase.
AB  - We report the identification and characterization of a novel lipid kinase that
      phosphorylates multiple substrates. This enzyme, which we term MuLK for multi
      substrate lipid kinase, does not belong to a previously described lipid kinase
      family. MuLK has orthologs in many organisms and is broadly expressed in human
      tissues. Although predicted to be a soluble protein, MuLK co-fractionates with
      membranes and localizes to an internal membrane compartment. Recombinant MuLK
      phosphorylates diacylglycerol, ceramide, and 1-acylglycerol but not sphingosine.
      Although its affinity for diacylglycerol and ceramide are similar, MuLK exhibits
      a higher V(max) toward diacylglycerol in vitro, consistent with it acting
      primarily as a diacylglycerol kinase. MuLK activity was inhibited by sphingosine
      and enhanced by cardiolipin. It was stimulated by calcium when magnesium
      concentrations were low and inhibited by calcium when magnesium concentrations
      were high. The effects of charged lipids and cations on MuLK activity in vitro
      suggest that its activity in vivo is tightly regulated by cellular conditions.

PMID- 15252047
TI  - Activated polyamine catabolism depletes acetyl-CoA pools and suppresses prostate
      tumor growth in TRAMP mice.
AB  - The enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) regulates the
      catabolism and export of intracellular polyamines. We have previously shown that
      activation of polyamine catabolism by conditional overexpression of SSAT has
      antiproliferative consequences in LNCaP prostate carcinoma cells. Growth
      inhibition was causally linked to high metabolic flux arising from a compensatory
      increase in polyamine biosynthesis. Here we examined the in vivo consequences of
      SSAT overexpression in a mouse model genetically predisposed to develop prostate
      cancer. TRAMP (transgenic adenocarcinoma of mouse prostate) female C57BL/6 mice
      carrying the SV40 early genes (T/t antigens) under an androgen-driven probasin
      promoter were cross-bred with male C57BL/6 transgenic mice that systemically
      overexpress SSAT. At 30 weeks of age, the average genitourinary tract weights of
      TRAMP mice were approximately 4 times greater than those of TRAMP/SSAT bigenic
      mice, and by 36 weeks, they were approximately 12 times greater indicating
      sustained suppression of tumor outgrowth. Tumor progression was also affected as
      indicated by a reduction in the prostate histopathological scores. By
      immunohistochemistry, SV40 large T antigen expression in the prostate epithelium
      was the same in TRAMP and TRAMP/SSAT mice. Consistent with the 18-fold increase
      in SSAT activity in the TRAMP/SSAT bigenic mice, prostatic N(1)-acetylspermidine
      and putrescine pools were remarkably increased relative to TRAMP mice, while
      spermidine and spermine pools were minimally decreased due to a compensatory 5-7
      fold increase in biosynthetic enzymes activities. The latter led to heightened
      metabolic flux through the polyamine pathway and an associated approximately 70%
      reduction in the SSAT cofactor acetyl-CoA and a approximately 40% reduction in
      the polyamine aminopropyl donor S-adenosylmethionine in TRAMP/SSAT compared with
      TRAMP prostatic tissue. In addition to elucidating the antiproliferative and
      metabolic consequences of SSAT overexpression in a prostate cancer model, these
      findings provide genetic support for the discovery and development of specific
      small molecule inducers of SSAT as a novel therapeutic strategy targeting
      prostate cancer.

PMID- 15252048
TI  - Effects of lipoprotein overproduction on the induction of DegP (HtrA) involved in
      quality control in the Escherichia coli periplasm.
AB  - Recent biochemical examination has revealed the presence of at least 90 different
      lipoproteins in Escherichia coli. Among previously identified lipoproteins, only
      an outer membrane lipoprotein, NlpE, is known to induce expression of the degP
      gene upon its overproduction. The degP gene encodes a periplasmic protease, which
      is thought to be involved in the digestion of unfolded proteins, and is essential
      for growth at high temperatures. However, it is not completely clear why NlpE
      overproduction causes degP expression. Moreover, among newly confirmed
      lipoproteins, there may be others that also induce degP expression. Therefore, we
      overproduced each of the 90 lipoproteins and examined the level of degP
      expression as beta-galactosidase activity by using a degP promoter-lacZ fusion.
      The extent of degP expression caused by NlpE overproduction was dependent on the
      mode of degP-lacZ fusion. On the other hand, new inner membrane lipoprotein YafY
      strongly induced degP expression irrespective of the mode of fusion even though
      the level of overproduced YafY was lower than that of NlpE. The induction of degP
      expression by YafY overproduction was dependent on the Cpx two-component system.
      Alteration of the lipoprotein-sorting signals of NlpE and YafY did not abolish
      the degP induction. However, a YafY derivative possessing the outer membrane
      signal remained on inner membranes. The non-lipidated derivative of NlpE did not
      induce degP expression, indicating that membrane anchoring is essential for degP
      induction. The amino acid sequences of YafY and YfjS, another inner membrane
      lipoprotein, are highly identical, but overproduction of the latter did not
      induce degP expression. Construction of various YafY-YfjS chimeric lipoproteins
      revealed that only a few residues located in the N- and C-terminal regions were
      important for the induction of DegP.

PMID- 15252049
TI  - Five residues in the HtrI transducer membrane-proximal domain close the
      cytoplasmic proton-conducting channel of sensory rhodopsin I.
AB  - Transducer-free sensory rhodopsins carry out light-driven proton transport in
      Halobacterium salinarum membranes. Transducer binding converts the proton pumps
      to signal-relay devices in which the transport is inhibited. In sensory rhodopsin
      I (SRI) binding of its cognate transducer HtrI inhibits transport by closing a
      cytoplasmic proton-conducting channel necessary for proton uptake during the SRI
      photochemical reaction cycle. To investigate the channel closure, a series of
      HtrI mutants truncated in the membrane-proximal cytoplasmic portion of an SRI
      HtrI fusion were constructed and expressed in H. salinarum membranes. We found
      that binding of the membrane-embedded portion of HtrI is insufficient for channel
      closure, whereas cytoplasmic extension of the second HtrI transmembrane helix by
      13 residues blocks proton conduction through the channel as well as full-length
      HtrI. Specifically the closure activity is localized in this 13-residue membrane
      proximal cytoplasmic domain to the 5 final residues, each of which incrementally
      contributes to reduction of proton conductivity. Moreover, these same residues in
      the dark incrementally and proportionally increase the pKa of the Asp-76
      counterion to the protonated Schiff base chromophore in the membrane-embedded
      photoactive site. We conclude that this critical region of HtrI alters the dark
      conformation of SRI as well as light-induced channel opening. The 5 residues in
      HtrI correspond in position to 5 residues demonstrated on the homologous NpHtrII
      to interact with the E-F loop of its cognate receptor NpSRII in the accompanying
      article (Yang, C.-S., Sineshchekov, O., Spudich, E. N., and Spudich, J. L. (2004)
      J. Biol. Chem. 279, 42970-42976). These results strongly suggest that the
      membrane-proximal region of Htr proteins interact with their cognate sensory
      rhodopsin cytoplasmic domains as part of the signal-relay coupling between the
      proteins.

PMID- 15252050
TI  - The cofactor function of the N-terminal domain of tissue factor.
AB  - Tissue factor (TF) is an integral membrane protein cofactor for factor VIIa
      (fVIIa) that initiates the blood coagulation cascade during vascular injury. TF
      has two fibrinonectin type III-like domains, both of which make extensive
      interactions with both the light and heavy chains of fVIIa. In addition to
      interaction with fVIIa, the membrane proximal C-terminal domain of TF is also
      known to bind the natural substrates factors IX and X, thereby facilitating their
      assembly and recognition by fVIIa in the activation complex. Both fVIIa and TF
      are elongated proteins, and their complex appears to be positioned nearly
      perpendicular to the membrane surface. It is possible that, similar to fVIIa, the
      N-terminal domain of TF also contacts the natural substrates. To investigate this
      possibility, we substituted all 23 basic and acidic residues of the N-terminal
      domain of TF with Ala or Asn and expressed the mutants as soluble TF(2-219) in a
      novel expression/purification vector system in the periplasmic space of bacteria.
      Following purification to homogeneity, the cofactor properties of mutants in
      promoting the amidolytic and proteolytic activity of fVIIa were analyzed in
      appropriate kinetic assays. The amidolytic activity assays indicated that several
      charged residues spatially clustered at the junction of the N- and C-terminal
      domains of TF are required for high affinity interaction with fVIIa. On the other
      hand, the proteolytic activity assays revealed that none of the residues under
      study may be an interactive site for either factor IX or factor X. However, it
      was discovered the Arg(74) mutant of TF was defective in enhancing both the
      amidolytic and proteolytic activity of fVIIa, suggesting that this residue may be
      required for the allosteric activation of the protease.

PMID- 15252051
TI  - Expression of ptsG encoding the major glucose transporter is regulated by ArcA in
      Escherichia coli.
AB  - Because the phosphoenolpyruvate:sugar phosphotransferase system plays multiple
      regulatory roles in addition to the phosphorylation-coupled transport of many
      sugars in bacteria, synthesis of its protein components is regulated in a highly
      sophisticated way. Thus far, the cAMP receptor protein (CRP) complex and Mlc are
      known to be the major regulators of ptsHIcrr and ptsG expression in response to
      the availability of carbon sources. In this report, we performed ligand fishing
      experiments by using the promoters of ptsHIcrr and ptsG as bait to find out new
      factors involved in the transcriptional regulation of the
      phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli, and we
      found that the anaerobic regulator ArcA specifically binds to the promoters.
      Deletion of the arcA gene caused about a 2-fold increase in the ptsG expression,
      and overexpression of ArcA significantly decreased glucose consumption. In vitro
      transcription assays showed that phospho-ArcA (ArcA-P) represses ptsG P1
      transcription. DNase I footprinting experiments revealed that ArcA-P binds to
      three sites upstream of the ptsG P1 promoter, two of which overlap the CRP
      binding sites, and the ArcA-P binding decreases the CRP binding that is essential
      for the ptsG P1 transcription. These results suggest that the response regulator
      ArcA regulates expression of enzyme IICB(Glc) mediating the first step of glucose
      metabolism in response to the redox conditions of growth in E. coli.

PMID- 15252052
TI  - Topological characterization of the c, c', and c" subunits of the vacuolar ATPase
      from the yeast Saccharomyces cerevisiae.
AB  - The vacuolar ATPase (V-ATPase) is a multisubunit enzyme that acidifies
      intracellular organelles in eukaryotes. Similar to the F-type ATP synthase
      (FATPase), the V-ATPase is composed of two subcomplexes, V(1) and V(0).
      Hydrolysis of ATP in the V(1) subcomplex is tightly coupled to proton
      translocation accomplished by the V(0) subcomplex, which is composed of five
      unique subunits (a, d, c, c', and c"). Three of the subunits, subunit c (Vma3p),
      c' (Vma11p), and c" (Vma16p), are small highly hydrophobic integral membrane
      proteins called "proteolipids" that share sequence similarity to the F-ATPase
      subunit c. Whereas subunit c from the F-ATPase spans the membrane bilayer twice,
      the V-ATPase proteolipids have been modeled to have at least four transmembrane
      spanning helices. Limited proteolysis experiments with epitope-tagged copies of
      the proteolipids have revealed that the N and the C termini of c (Vma3p) and c'
      (Vma11p) were in the lumen of the vacuole. Limited proteolysis of epitope-tagged
      c" (Vma16p) indicated that the N terminus is located on the cytoplasmic face of
      the vacuole, whereas the C terminus is located within the vacuole. Furthermore, a
      chimeric fusion between Vma16p and Vma3p, Vma16-Vma3p, was found to assemble into
      a fully functional V-ATPase complex, further supporting the conclusion that the C
      terminus of Vma16p resides within the lumen of the vacuole. These results
      indicate that subunits c and c' have four transmembrane segments with their N and
      C termini in the lumen and that c" has five transmembrane segments, with the N
      terminus exposed to the cytosol and the C terminus lumenal.

PMID- 15252053
TI  - A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the
      crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily:
      structural evidence at 1.16-A resolution.
AB  - The crystal structure of a dual specificity phosphoglucose isomerase
      (PGI)/phosphomannose isomerase from Pyrobaculum aerophilum (PaPGI/PMI) has been
      determined in native form at 1.16-A resolution and in complex with the enzyme
      inhibitor 5-phosphoarabinonate at 1.45-A resolution. The similarity of its fold,
      with the inner core structure of PGIs from eubacterial and eukaryotic sources,
      confirms this enzyme as a member of the PGI superfamily. The almost total
      conservation of amino acids in the active site, including the glutamate base
      catalyst, shows that PaPGI/PMI uses the same catalytic mechanisms for both ring
      opening and isomerization for the interconversion of glucose 6-phosphate (Glc-6
      P) to fructose 6-phosphate (Fru-6-P). The lack of structural differences between
      native and inhibitor-bound enzymes suggests this activity occurs without any of
      the conformational changes that are the hallmark of the well characterized PGI
      family. The lack of a suitable second base in the active site of PaPGI/PMI argues
      against a PMI mechanism involving a trans-enediol intermediate. Instead, PMI
      activity may be the result of additional space in the active site imparted by a
      threonine, in place of a glutamine in other PGI enzymes, which could permit
      rotation of the C-2-C-3 bond of mannose 6-phosphate.

PMID- 15252055
TI  - Individual nucleotide bases, not base pairs, are critical for triggering site
      specific DNA cleavage by vaccinia topoisomerase.
AB  - Vaccinia DNA topoisomerase forms a covalent DNA-(3'-phosphotyrosyl)-enzyme
      intermediate at a specific target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p downward
      arrow N(-1) in duplex DNA. Here we study the effects of abasic lesions at
      individual positions of the scissile and nonscissile strands on the rate of
      single-turnover DNA transesterification and the cleavage-religation equilibrium.
      The rate of DNA incision was reduced by factors of 350, 250, 60, and 10 when
      abasic sites replaced the -1N, +1T, +2T, and +4C bases of the scissile strand,
      but abasic lesions at +5C and +3C had little or no effect. Abasic lesions in the
      nonscissile strand in lieu of +4G, +3G, +2A, and +1A reduced the rate of cleavage
      by factors of 130, 150, 10, and 5, whereas abasic lesions at +5G and -1N had no
      effect. The striking positional asymmetry of abasic interference on the scissile
      and nonscissile strands highlights the importance of individual bases, not base
      pairs, in promoting DNA cleavage. The rate of single-turnover DNA religation by
      the covalent topoisomerase-DNA complex was insensitive to abasic sites within the
      CCCTT sequence of the scissile strand, but an abasic lesion at the 5'-OH
      nucleoside (-1N) of the attacking DNA strand slowed the rate of religation by a
      factor of 600. Nonscissile strand abasic lesions at +1A and -1N slowed the rate
      of religation by factors of approximately 140 and 20, respectively, and strongly
      skewed the cleavage-religation equilibrium toward the covalent complex. Thus,
      abasic lesions immediately flanking the cleavage site act as topoisomerase
      poisons.

PMID- 15252054
TI  - Directed evolution of a glycosynthase from Agrobacterium sp. increases its
      catalytic activity dramatically and expands its substrate repertoire.
AB  - The Agrobacterium sp. beta-glucosidase (Abg) is a retaining beta-glycosidase and
      its nucleophile mutants, termed Abg glycosynthases, catalyze the formation of
      glycosidic bonds using alpha-glycosyl fluorides as donor sugars and various aryl
      glycosides as acceptor sugars. Two rounds of random mutagenesis were performed on
      the best glycosynthase to date (AbgE358G), and transformants were screened using
      an on-plate endocellulase coupled assay. Two highly active mutants were obtained,
      1D12 (A19T, E358G) and 2F6 (A19T, E358G, Q248R, M407V) in the first and second
      rounds, respectively. Relative catalytic efficiencies (kcat/Km) of 1:7:27 were
      determined for AbgE358G, 1D12, and 2F6, respectively, using alpha-D
      galactopyranosyl fluoride and 4-nitrophenyl beta-D-glucopyranoside as substrates.
      The 2F6 mutant is not only more efficient but also has an expanded repertoire of
      acceptable substrates. Analysis of a homology model structure of 2F6 indicated
      that the A19T and M407V mutations do not interact directly with substrates but
      exert their effects by changing the conformation of the active site. Much of the
      improvement associated with the A19T mutation seems to be caused by favorable
      interactions with the equatorial C2-hydroxyl group of the substrate. The
      alteration of torsional angles of Glu-411, Trp-412, and Trp-404, which are
      components of the aglycone (+1) subsite, is an expected consequence of the A19T
      and M407V mutations based on the homology model structure of 2F6.

PMID- 15252057
TI  - Dimer dissociation is essential for interleukin-8 (IL-8) binding to CXCR1
      receptor.
AB  - Chemokines play a fundamental role in trafficking of immune cells and in host
      defense against infection. The role of chemokines in the recruitment process is
      highly regulated spatially and temporally and involves interactions with G
      protein-coupled receptors and cell surface glycosaminoglycans. The dynamic
      equilibrium between chemokine monomers and dimers, both free in solution and in
      cell surface-bound forms, regulates different components of recruitment such as
      chemotaxis and receptor signaling. The binding and activity of the chemokine
      interleukin-8 (IL-8) for its receptors, previously studied using "trapped" non
      associating monomers and non-dissociating dimers, show that the monomer has a
      native-like function but support conflicting roles for the dimer. We have
      measured the binding of native IL-8 to the CXCR1 N-domain, using isothermal
      titration calorimetry and sedimentation equilibrium techniques. The N-domain
      constitutes a critical binding site, and IL-8 binding affinity to the receptor N
      domain is in the same concentration range as the IL-8 monomerdimer equilibrium.
      We observed that only the IL-8 monomer, and not the dimer, is competent in
      binding the receptor N-domain. Based on our results, we propose that IL-8
      dimerization functions as a negative regulator for the receptor function and as a
      positive regulator for binding to glycosaminoglycans and that both play a role in
      the neutrophil recruitment process.

PMID- 15252056
TI  - The HoxC4 homeodomain protein mediates activation of the immunoglobulin heavy
      chain 3' hs1,2 enhancer in human B cells. Relevance to class switch DNA
      recombination.
AB  - The immunoglobulin heavy chain (IgH) 3' regulatory region modulates IgH locus
      transcription, upon induction by specific trans-acting factors, and plays a
      significant role in class switch DNA recombination (CSR) and, perhaps, somatic
      hypermutation (SHM). CSR and SHM are central to the maturation of the antibody
      response. In contrast to the single 5'-hs3a-hs1,2-hs3b-hs4-3 ' mouse IgH 3 '
      regulatory region, the human IgH 3 ' regulatory region exists as a 5'-hs3-hs1,2
      hs4-3' cluster duplicated 3 ' of Calpha1 and Calpha2. We show here that the human
      hs1,2 element is the strongest enhancer of transcription, as directed by a V(H)1
      or the ECS-Igamma3 promoter, thereby suggesting a dominant role for hs1,2 over
      hs3 and hs4 in the overall activity of the 3 ' regulatory region. Within hs1,2,
      we identified three regions (1, 2, and 3) that are all necessary, but
      individually not sufficient, for enhancement of transcription. In region 2, a
      HoxC4 site and a HoxC4/embedded octamer (HoxC4/Oct) site are conserved across
      human, mouse, rat, and rabbit. These two sites recruit HoxC4 and Oct-1/Oct-2,
      which act synergistically with the Oca-B coactivator to effect the full hs1,2
      enhancing activity. HoxC4, Oct-1/Oct-2, and Oca-B recruitment is negligible in
      pro-B cells, moderate in pre-B cells, and maximal in germinal center B cells and
      plasma cells, where HoxC4, Oct-2, and Oca-B expression correlates with hs1,2
      activation and ongoing CSR. The hs1,2mediated enhancement of V(H) and C(H)
      promoter-driven transcription as induced by HoxC4 and Oct-1/Oct-2 suggests an
      important role of these homeodomain proteins in the overall regulation of the IgH
      locus expression.

PMID- 15252058
TI  - The ATC1 gene encodes a cell wall-linked acid trehalase required for growth on
      trehalose in Candida albicans.
AB  - After screening a Candida albicans genome data base, the product of an open
      reading frame (IPF 19760/CA2574) with 41% identity to Saccharomyces cerevisiae
      vacuolar acid trehalase (Ath1p) was identified and named Atc1p. The deduced amino
      acid sequence shows that Atc1p contains an N-terminal hydrophobic signal peptide
      and 20 potential sites for N-glycosylation. C. albicans homozygous mutants that
      lack acid trehalase activity were constructed by gene disruption at the two ATC
      chromosomal alleles. Analysis of these null mutants shows that Atc1p is localized
      in the cell wall and is required for growth on trehalose as a carbon source. An
      Atc1p endowed with acid trehalase activity was obtained by an in vtro
      transcription-translation coupled system. These results strongly suggest that
      ATC1 is the structural gene encoding cell wall acid trehalase in C. albicans.
      Determinations of ATC1 mRNA expression as well as acid trehalase activity in the
      presence and absence of glucose point out that ATC1 gene is regulated by glucose
      repression.

PMID- 15252060
TI  - From charity to rights: proposal for five action areas of global health.

PMID- 15252059
TI  - Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic
      reticulum-associated degradation of a multispanning membrane protein and a
      soluble luminal protein.
AB  - The folding and assembly of proteins in the endoplasmic reticulum (ER) lumen and
      membrane are monitored by ER quality control. Misfolded or unassembled proteins
      are retained in the ER and, if they cannot fold or assemble correctly, ultimately
      undergo ER-associated degradation (ERAD) mediated by the ubiquitin-proteasome
      system. Whereas luminal and integral membrane ERAD substrates both require the
      proteasome for their degradation, the ER quality control machinery for these two
      classes of proteins likely differs because of their distinct topologies. Here we
      establish the requirements for the ERAD of Ste6p*, a multispanning membrane
      protein with a cytosolic mutation, and compare them with those for mutant form of
      carboxypeptidase Y (CPY*), a soluble luminal protein. We show that turnover of
      Ste6p* is dependent on the ubiquitin-protein isopeptide ligase Doa10p and is
      largely independent of the ubiquitin-protein isopeptide ligase Hrd1p/Der3p,
      whereas the opposite is true for CPY*. Furthermore, the cytosolic Hsp70 chaperone
      Ssa1p and the Hsp40 co-chaperones Ydj1p and Hlj1p are important in ERAD of
      Ste6p*, whereas the ER luminal chaperone Kar2p is dispensable, again opposite
      their roles in CPY* turnover. Finally, degradation of Ste6p*, unlike CPY*, does
      not appear to require the Sec61p translocon pore but, like CPY*, could depend on
      the Sec61p homologue Ssh1p. The ERAD pathways for Ste6p* and CPY* converge at a
      post-ubiquitination, pre-proteasome step, as both require the ATPase Cdc48p. Our
      results demonstrate that ERAD of Ste6p* employs distinct machinery from that of
      the soluble luminal substrate CPY* and that Ste6p* is a valuable model substrate
      to dissect the cellular machinery required for the ERAD of multispanning membrane
      proteins with a cytosolic mutation.

PMID- 15252061
TI  - The dangers of "spin": information, science, security, and welfare.

PMID- 15252062
TI  - Data, "race," and politics: a commentary on the epidemiological significance of
      California's Proposition 54.

PMID- 15252063
TI  - Two information dissemination approaches for public health decision makers:
      encyclopaedia and fire alarm.

PMID- 15252065
TI  - Health impact assessment for the sustainable futures of Salford.
AB  - BACKGROUND: The Salford Health Investment for Tomorrow and the Local Improvement
      Finance Trust proposals for the comprehensive redevelopment of Salford Royal
      Hospital and the provision of four integrated primary health and social centres
      in the City of Salford are a response to the challenge of the NHS Plan to
      modernize delivery and service provision. The scale of the proposed developments
      will have a major effect on the quality of life in Salford. This health impact
      assessment was undertaken to determine how these proposals could be amended to
      ensure that the impacts are optimised so that potential benefits to Salford's
      communities are realised to maximise their health and wellbeing. METHOD: This
      involved a comprehensive prospective health impact assessment and a series of
      interviews with key stakeholders, community organisations, and local people to
      identify and prioritize potential positive and negative impacts of the proposals.
      RESULTS AND CONCLUSIONS: The assessment pointed to a wide range of positive and
      negative impacts that provided the basis of a set of recommendations, which were
      linked directly to the themes of the Salford Community Plan. These related to
      setting employment, education, and training opportunities to maximise health and
      wellbeing and improve quality of life for all communities in Salford within the
      framework of the plan. In presenting the findings of the health impact assessment
      and discussing the recommendations, the paper presents a unique approach in
      health impact assessment reporting by offering perspectives from the assessor and
      the project's steering group.

PMID- 15252064
TI  - Bias.
AB  - The concept of bias is the lack of internal validity or incorrect assessment of
      the association between an exposure and an effect in the target population in
      which the statistic estimated has an expectation that does not equal the true
      value. Biases can be classified by the research stage in which they occur or by
      the direction of change in a estimate. The most important biases are those
      produced in the definition and selection of the study population, data
      collection, and the association between different determinants of an effect in
      the population. A definition of the most common biases occurring in these stages
      is given.

PMID- 15252066
TI  - Did Finland's Tobacco Control Act of 1976 have an impact on ever smoking? An
      examination based on male and female cohort trends.
AB  - OBJECTIVE: To examine patterns of ever smoking among Finnish adults by gender and
      birth cohort from 1978 to 2001, with special emphasis on the possible effects of
      the 1976 Tobacco Control Act (TCA). METHODS: The data were derived from
      independent, annual cross sectional postal surveys among 15-64 year olds (n =
      91,342), average response rate 75%. For the analyses 13 five year birth cohorts
      from 1916 to 1980 were constructed. Birth cohort variations in ever regular
      smoking were first examined graphically, and then logistic models were used to
      test the impact of the TCA. RESULTS: Among men there was a decrease in smoking
      from older to younger cohorts. For women an increase in smoking was observed
      between successive cohorts. A clear decline in the prevalence of ever smokers
      concurrent with the TCA was found among both men and women. CONCLUSIONS: The
      smoking behaviour trends across successive birth cohorts suggest the impact of
      tobacco policy in decreasing smoking initiation in youth. These findings thus
      support the acceptability and effectiveness of antismoking and smoke free policy
      measures in society.

PMID- 15252067
TI  - Equity of access to health care: outlining the foundations for action.
AB  - The Ministers of Health from Chile, Germany, Greece, New Zealand, Slovenia,
      Sweden, and the United Kingdom recently established The International Forum on
      Common Access to Health Care Services, based on a common belief that their
      citizens should enjoy universal and equitable access to good quality health care.
      The ministers intend to form a network to share thinking and evidence on health
      care improvements, with the specific aim of sustaining and promoting equitable
      access to health care. Despite a vast literature on the notion of equity of
      access, little agreement has been reached in the literature on exactly what this
      notion ought to mean. This article provides a brief description of the relevance
      of the access principle of equity, and summarises the research programme that is
      necessary for turning the principle into a useful, operational policy objective.

PMID- 15252068
TI  - Compression, expansion, or dynamic equilibrium? The evolution of health
      expectancy in New Zealand.
AB  - STUDY OBJECTIVE: To evaluate the New Zealand evidence for three theories of
      population health change: compression of morbidity, expansion of morbidity, and
      dynamic equilibrium. DESIGN: Using the Sullivan method, repeated cross sectional
      survey information on functional limitation prevalence was combined with
      population mortality data and census information on the utilisation of
      institutional care to produce health expectancy indices for 1981 and 1996.
      SETTING: The adult population of New Zealand in 1981 and 1996. PARTICIPANTS: 6891
      respondents to the 1981 social indicators survey; 8262 respondents to the 1996
      household disability survey. MAIN RESULTS: As a proportion of overall life
      expectancy at age 15 the expectation of non-institutionalised mobility
      limitations increased from 3.5% to 6% for men, and from 4.5% to 8% for women; the
      expectation of agility limitation increased from 3% to 7.5% for men and from 4.5%
      to 8.5% for women, and the expectation of self care limitations increased from
      2.0% to 4.5% for men and from 3.0% to 6.0% for women. These changes were
      primarily attributable to increases in the expectation of moderate functional
      limitation. CONCLUSION: The dynamic equilibrium scenario provides the best fit to
      current New Zealand evidence on changes in population health. Although an aging
      population is likely to lead to an increase in demand for disability support
      services, the fiscal impact of this increase may be partially offset by a shift
      from major to moderate limitations, with a consequential reduction in the average
      levels of support required.

PMID- 15252069
TI  - Association of quality of life in old age in Britain with socioeconomic position:
      baseline data from a randomised controlled trial.
AB  - STUDY OBJECTIVE: To identify socioeconomic differentials in quality of life among
      older people and their explanatory factors. DESIGN: Baseline data from a cluster
      randomised controlled trial of the assessment and management of older people in
      primary care. Outcome measures were being in the worst quintile of scores for,
      respectively, the Philadelphia geriatric morale scale and four dimensions of
      functioning from the sickness impact profile (home management, mobility, self
      care, and social interaction). SETTING: 23 general practices in Britain.
      PARTICIPANTS: People aged 75 years and over on GP registers at the time of
      recruitment, excluding those in nursing homes or terminally ill. Of 9547 people
      eligible, 90% provided full information on quality of life and 6298 also did a
      brief assessment. RESULTS: The excess risk of poor quality of life for
      independent people renting rather than owning their home ranged from 27% for
      morale (95% CI 9% to 48%) to 62% for self care (95% CI 35% to 94%). Self reported
      health problems plus smoking and alcohol consumption accounted for half or more
      of the excess, depending on the outcome. Having a low socioeconomic position in
      middle age as well as in old age exacerbated the risks of poor outcomes. Among
      people living with someone other than spouse the excess risk from renting ranged
      from 24% (95% CI -10% to 70%) for poor home management to 93% (95% CI 30% to
      180%) for poor morale. CONCLUSIONS: Older people retain the legacy of past
      socioeconomic position and are subject to current socioeconomic influences.

PMID- 15252070
TI  - Cognitive performance in childhood and early adult illness: a prospective cohort
      study.
AB  - STUDY OBJECTIVE: To evaluate whether cognitive performance in childhood is an
      early determinant of adult illness. DESIGN: Prospective cohort study covering
      over 30 years. SETTING: Providence, Rhode Island, USA. PARTICIPANTS: 633 people
      ages 30-39 followed up since birth as part of the Providence cohort of the
      national collaborative perinatal project. MAIN RESULTS: Higher cognitive
      performance at age 7 was related to a significantly reduced risk of serious
      illness in adulthood, OR = 0.65 (95%CI: 0.47 to 0.89) for a one standard
      deviation (15 point) increase in IQ score. This association was independent of
      both parental socioeconomic status and participant's attained level of education.
      CONCLUSIONS: General cognitive performance may be an important and informative
      early determinant of adult health. Further evaluation of this association and
      mechanisms linking cognitive performance and health may provide new and
      innovative strategies to improve disease management and reduce morbidity.

PMID- 15252071
TI  - Unintentional and violent injuries among pre-school children of teenage mothers
      in Sweden: a national cohort study.
AB  - STUDY OBJECTIVE: This study investigates the risk and mediating mechanisms of
      unintentional and violent injuries in pre-school children of teenage mothers.
      DESIGN: Cohort study based on Swedish national registers. Cox analyses of
      proportional hazard were used to estimate the relative risk of hospital admission
      and death attributable to injuries in analyses of data from national registers.
      PARTICIPANTS: The study population was a national cohort of 800,192 children born
      in Sweden during 1987-93 who were followed up prospectively from birth to their
      7th birthday. MAIN RESULTS: Children of teenage mothers had higher relative risks
      (RRs) of hospital admissions for violent as well as unintentional injuries; age
      adjusted RRs of 2.7 (95% CI 1.2 to 6.1) and 1.6 (1.4 to 1.8), respectively, for
      children of mothers under 18 years of age and 2.5 (1.6 to 3.8) and 1.5 (1.4 to
      1.6) of mothers aged 18-19 are compared with those with mothers aged at least 32
      at the birth of the child. When the models were adjusted to socioeconomic
      variables and indicators of parental substance misuse and psychiatric illness the
      risk decreased slightly but remained well above that of children with older
      mothers. In addition, children of teenage mothers had an increased risk of death
      attributable to violent injuries (RR 6.7 (2.6 to 16.0), as well as to
      unintentional injuries (RR 3.5 (2.0 to 6.1). CONCLUSIONS: Maternal age is an
      important determinant of injuries in pre-school children in Sweden and the
      children of teenage mothers are at particular risk. Young parents should be given
      priority in injury prevention programmes.

PMID- 15252072
TI  - Residential area deprivation predicts fruit and vegetable consumption
      independently of individual educational level and occupational social class: a
      cross sectional population study in the Norfolk cohort of the European
      Prospective Investigation into Cancer (EPIC-Norfolk).
AB  - STUDY OBJECTIVE: To investigate the independent association between individual
      and area based socioeconomic measures and fruit and vegetable consumption.
      DESIGN: Cross sectional population based study. SETTING AND PARTICIPANTS: 22,562
      men and women aged 39-79 years living in the general community in Norfolk, United
      Kingdom, recruited using general practice age-sex registers. OUTCOME MEASURES:
      Fruit and vegetable intake assessed using a food frequency questionnaire. MAIN
      RESULTS: Being in a manual occupational social class, having no educational
      qualifications, and living in a deprived area all independently predicted
      significantly lower consumption of fruit and vegetables. The effect of
      residential area deprivation was predominantly in those in manual occupational
      social class and no educational qualifications. CONCLUSIONS: Understanding some
      of the community level barriers to changing health related behaviours may lead to
      more effective interventions to improving health in the whole community,
      particularly those who are most vulnerable.

PMID- 15252073
TI  - Associations of smoking prevalence with individual and area level social
      cohesion.
AB  - STUDY OBJECTIVE: To discover if area level social cohesion, neighbourhood safety,
      and home safety are associated with current cigarette smoking among adults after
      adjustment for concentrations of poverty and low education. DESIGN: Cross
      sectional survey of a random sample of adults, stratified by 19 geographical
      areas. SETTING: SHAPE, Survey of the Health of Adults, the Population, and the
      Environment-conducted in 1998 by the Hennepin County Community Health Department
      and the Minneapolis Department of Health and Family Support in Minnesota.
      PARTICIPANTS: 5256 men and 4806 women, 18 years and older, randomly selected from
      19 geographical areas in an urban county. MAIN RESULTS: Overall, 21.2% of survey
      respondents reported current cigarette smoking. Both higher area level social
      cohesion (OR = 0.85, 95% CI = 0.74 to 0.98) and higher individual social cohesion
      (OR = 0.96, 95% CI = 0.92 to 0.99) were associated with lower likelihoods of
      smoking. Similar models were obtained for neighbourhood safety and home safety.
      CONCLUSIONS: These findings contribute to the growing literature on the important
      role of social cohesion and other area level characteristics on smoking behaviour
      among adults.

PMID- 15252074
TI  - Self perceived health and smoking in adolescents.

PMID- 15252075
TI  - Sex differences in body fat distribution and carotid intima media thickness:
      cross sectional survey using data from the British regional heart study.
AB  - OBJECTIVE: To determine the role of central adiposity in explaining sex
      differences in carotid intima media thickness (IMT). DESIGN: Cross sectional
      survey. SETTING: Two British towns. PARTICIPANTS: 800 men and women aged 56-75
      years. MAIN OUTCOME MEASURES: Carotid IMT. RESULTS: There was a continuous linear
      association between waist-hip ratio and IMT in both men and women. The magnitude
      of the association between waist to hip ratio and IMT was identical in both
      sexes. In age adjusted analyses IMT was 14% greater in men compared with women
      (age adjusted male to female ratio of geometric means 1.14; 95% confidence
      interval 1.07 to 1.21) with adjustment for waist to hip ratio this attenuated to
      no difference (1.00; 0.92 to 1.09). Adjustment for body mass index and for
      lifestyle risk factors had very little effect on the sex difference in mean
      intima media thickness. CONCLUSIONS: Sex differences in body fat distribution may
      explain sex differences in arterial atherosclerosis.

PMID- 15252076
TI  - Can cardiovascular risk factors and lifestyle explain the educational
      inequalities in mortality from ischaemic heart disease and from other heart
      diseases? 26 year follow up of 50,000 Norwegian men and women.
AB  - OBJECTIVE: Investigate the degree to which smoking, physical activity, marital
      status, BMI, blood pressure, and cholesterol explain the association between
      educational level and ischaemic heart disease (IHD) mortality and other forms of
      cardiovascular mortality, with main focus on IHD mortality. DESIGN: Prospective
      health examination survey study conducted in the period 1974-78. SETTING:
      Oppland, Sogn og Fjordane, and Finnmark counties in Norway. PARTICIPANTS: The
      sample comprised 22,712 men and 21,972 women, aged 35-49 at screening. The
      subjects were followed up with respect to mortality throughout year 2000. MAIN
      RESULTS: 4342 men and 2164 women died during the follow up, 1343 men and 258
      women of IHD. IHD mortality risk was higher for people with low education
      compared with people with high education, and people with low education had more
      adverse risk factors. After adjustment for smoking the IHD mortality relative
      risk (RR) with 95% confidence limits, in the low educational group decreased from
      1.33 (1.18 to 1.50) to 1.16 (1.03 to 1.31) for men, and from 1.72 (1.23 to 2.41)
      to 1.58 (1.13 to 2.22) for women. Further adjustment for physical activity,
      marital status, BMI, blood pressure, and cholesterol reduced the RR to 1.03 (0.91
      to 1.17) for men and 1.24 (0.88 to 1.75) for women. CONCLUSIONS: Unfavourable
      cardiovascular risk factors and high IHD mortality are more prevalent among less
      educated than their highly educated peers. After simultaneous adjustment for all
      recorded risk factors, the excess IHD mortality in the low educational groups was
      reduced by 91% for men and 67% for women.

PMID- 15252077
TI  - Sickness absence as a risk marker of future disability pension: the 10-town
      study.

PMID- 15252078
TI  - A simple model for potential use with a misclassified binary outcome in
      epidemiology.
AB  - STUDY OBJECTIVE: Error in determination of disease outcome occurs in
      epidemiology, but such error is not usually corrected for in statistical
      analysis. A method of correction of risk estimates for misclassification of a
      binary disease outcome is developed here. METHODS: The method is a simple, closed
      form correction to the logistic regression estimate. A closed form variance
      estimate is also developed. SETTING: The method is illustrated in two studies, a
      cross sectional survey of cervicitis in Iran in 1996-97, as determined by
      inflammation on cervical smear specimens, and a case-cohort study of benign
      proliferative epithelial disease of the breast, in Canada 1980-88. MAIN RESULTS:
      The method provides corrected odds ratio estimates and corrects the spurious
      precision conferred by misclassification. CONCLUSIONS: The method is easy to
      apply and potentially useful, although potential failures of the assumptions
      involved should be borne in mind. It is necessary to give careful consideration
      to the plausibility or otherwise of the assumptions in the context of the
      individual study. Correction for misclassification of disease outcome may become
      more common with the development of readily applicable methods.

PMID- 15252079
TI  - Inter-rater agreement in defining chemical incidents at the National Poisons
      Information Service, London.
AB  - BACKGROUND: National surveillance for chemical incidents is being developed in
      the UK. It is important to improve the quality of information collected,
      standardise techniques, and train personnel. OBJECTIVE: To define the extent to
      which eight National Poison Information Service specialists in poison information
      agree on the classification of calls received as "chemical incidents" based on
      the national definition. DESIGN: Blinded, inter-rater reliability measured using
      the kappa statistic for multiple raters. SETTING: National Poison Information
      Service and Chemical Incident Response Service, Guy's and St Thomas's NHS Trust,
      London. PARTICIPANTS: Eight specialists in poison information who are trained and
      experienced in handling poisons information calls and have been involved in
      extracting information for surveillance. RESULTS: The overall level of agreement
      observed was at least 69% greater than expected by chance (kappa statistic). Fire
      and incidents where chemicals were released within a property had a very good
      level of agreement with kappa statistic of 83% and 80% respectively. The lowest
      level of agreement was observed when no one or only one person was exposed to a
      chemical (33%) and when the chemical was released into the air (48%). CONCLUSION:
      High levels of agreement were observed. There is a need for more training and
      improvement in consistency of the data collected by all organisations.

PMID- 15252080
TI  - Comparison of primary total hip replacements performed with a standard incision
      or a mini-incision.
AB  - BACKGROUND: Primary total hip replacement performed through an incision that is
      </=10 cm in length has been advocated as a minimally invasive technique.
      Proponents have claimed that mini-incision techniques reduce blood loss,
      transfusion requirements, postoperative pain, and the length of the hospital stay
      compared with standard techniques through a longer incision. However, we are
      aware of no well-designed comparison study that supports these claims. The
      purpose of the present study was to compare the short-term results of a mini
      incision with a standard incision technique for total hip replacement. METHODS: A
      consecutive series of patients who underwent 135 primary unilateral total hip
      replacements (fifty with use of a mini-incision [</=10 cm] and eighty-five with
      use of a standard incision) by three surgeons at one hospital were studied. Each
      surgeon selected patients to have a mini-incision procedure and performed a
      standard approach in the remaining patients. A posterior approach was used for
      all procedures. In-hospital data were collected retrospectively, and the initial
      postoperative radiographs were analyzed. Because of the selection process, the
      patients who had a mini-incision had both a significantly lower average body-mass
      index (p = 0.008) and a lower average score on the American Society of
      Anesthesiologists rating (p = 0.006), indicating that they were thinner and
      healthier than the patients who had a standard incision. RESULTS: With the
      numbers of patients available, no significant differences were found between the
      groups with respect to the average surgical time, intraoperative blood loss, in
      hospital transfusion rate, length of hospital stay, or the patients' disposition
      after discharge. The mini-incision group was found to have a significantly higher
      risk of a wound complication (p = 0.02), a higher percentage of acetabular
      component malposition (p = 0.04), and poor fit and fill of femoral components
      inserted without cement (p = 0.0036). CONCLUSIONS: There was no evidence that the
      mini-incision technique resulted in less bleeding or less trauma to the soft
      tissues of the hip, factors that would have produced a quicker recovery and a
      shorter hospital stay, than did the standard technique. The present study, which
      was based on the authors' initial experience with the mini-incision technique,
      failed to confirm the positive clinical outcomes reported by previous
      uncontrolled cohort studies, and the findings suggest that further analysis of
      this new technique is needed before it can be recommended for general use.

PMID- 15252081
TI  - Estimating the risk of nonunion following nonoperative treatment of a clavicular
      fracture.
AB  - BACKGROUND: Nonunion is a rare complication of a fracture of the clavicle, but
      its occurrence can compromise shoulder function. The aim of this study was to
      evaluate the prevalence of and risk factors for nonunion in a cohort of patients
      who were treated nonoperatively after a clavicular fracture. METHODS: Over a
      fifty-one-month period, we performed a prospective, observational cohort study of
      a consecutive series of 868 patients (638 men and 230 women with a median age of
      29.5 years; interquartile range, 19.25 to 46.75 years) with a radiographically
      confirmed fracture of the clavicle, which was treated nonoperatively. Eight
      patients were excluded from the study, as they received immediate surgery.
      Patients were evaluated clinically and radiographically at six, twelve, and
      twenty-four weeks after the injury. There were 581 fractures in the diaphysis,
      263 fractures in the lateral fifth of the clavicle, and twenty-four fractures in
      the medial fifth. RESULTS: On survivorship analysis, the overall prevalence of
      nonunion at twenty-four weeks after the fracture was 6.2%, with 8.3% of the
      medial end fractures, 4.5% of the diaphyseal fractures, and 11.5% of the lateral
      end fractures remaining ununited. Following a diaphyseal fracture, the risk of
      nonunion was significantly increased by advancing age, female gender,
      displacement of the fracture, and the presence of comminution (p < 0.05 for all).
      On multivariate analysis, all of these factors remained independently predictive
      of nonunion, and, in the final model, the risk of nonunion was increased by lack
      of cortical apposition (relative risk = 0.43; 95% confidence interval = 0.34 to
      0.54), female gender (relative risk = 0.70; 95% confidence interval = 0.55 to
      0.89), the presence of comminution (relative risk = 0.69; 95% confidence interval
      = 0.52 to 0.91), and advancing age (relative risk = 0.99; 95% confidence interval
      = 0.99 to 1.00). Following a lateral end fracture, the risk of nonunion was
      significantly increased only by advancing age and displacement of the fracture (p
      < 0.05 for both). On multivariate analysis, both of these factors remained
      independently predictive of nonunion (p < 0.05), and, in the final model, the
      risk of nonunion was increased by a lack of cortical apposition (relative risk =
      0.38; 95% confidence interval = 0.25 to 0.57) and advancing age (relative risk =
      0.98; 95% confidence interval = 0.97 to 0.99). CONCLUSIONS: Nonunion at twenty
      four weeks after a clavicular fracture is an uncommon occurrence, although the
      prevalence is higher than previously reported. There are subgroups of individuals
      who appear to be predisposed to the development of this complication, either from
      intrinsic factors, such as age or gender, or from the type of injury sustained.
      The predictive models that we developed may be used clinically to counsel
      patients about the risk for the development of this complication immediately
      after the injury.

PMID- 15252082
TI  - The moving target: a qualitative study of elderly patients' decision-making
      regarding total joint replacement surgery.
AB  - BACKGROUND: Total joint replacement is an accepted, cost-effective, and
      underutilized treatment for moderate-to-severe hip and knee arthritis. Yet,
      research has suggested that many patients with arthritis are unwilling to
      consider total joint replacement surgery. We sought to understand these patients'
      unwillingness by exploring the nature of their decision-making processes.
      METHODS: In-depth interviews were conducted with seventeen individuals with
      moderate-to-severe arthritis who were appropriate candidates for, but unwilling
      to consider, total joint replacement. The interviews were analyzed with use of
      qualitative methods and content analysis techniques. RESULTS: Symptoms and
      information sources were the two main factors influencing patient decision
      making. Participants engaged in individualized processes of trading off perceived
      costs and benefits. Accommodation to pain and disability and minimization of the
      quality-of-life benefit, in view of decreasing life span, led to a process
      whereby the threshold at which the benefits compared with the risks would tilt in
      favor of total joint replacement was constantly shifting, a phenomenon we called
      "the moving target." CONCLUSIONS AND CLINICAL RELEVANCE: The moving-target
      characterization sheds light on patients' conceptions of their arthritis and on
      their unwillingness to consider total joint replacement. This process needs to be
      considered when developing ways to aid decision-making.

PMID- 15252083
TI  - Evaluation of Morton's theory of second metatarsal hypertrophy.
AB  - BACKGROUND: Originally introduced by Morton, the concept of hypertrophy of the
      medial cortex and the entire shaft of the second metatarsal as an objective sign
      of increased mobility of the first ray has not been subjected to much scrutiny.
      The goal of the current study was to assess the clinical relevance and
      reliability of radiographic measures of hypertrophy of the second metatarsal in
      relation to mobility of the first ray, pes planus, and tightness of the
      gastrocnemiussoleus in both control subjects and patients with diagnosed
      disorders of the forefoot. METHODS: Four study groups of forty-three subjects
      each were evaluated. The cohort included an asymptomatic control group as well as
      three groups made up of patients with symptoms and a diagnosis of hallux valgus,
      hallux rigidus, or interdigital neuroma. Mobility of the first ray (as measured
      with a device and method described by Klaue et al.), arch height, and ankle
      dorsiflexion were measured on physical examination. Plain weight-bearing
      radiographs and previously established equations were used to determine
      hypertrophy and the length of the second metatarsal, and the hallux valgus and
      first-second intermetatarsal angles were measured on plain radiographs as well.
      RESULTS: There was no significant difference between the control and symptomatic
      groups with regard to the values for hypertrophy of the second metatarsal. The
      patients with hallux valgus deformity had significantly greater mobility of the
      first ray (p < 0.001) compared with the controls. No correlation was found
      between values for hypertrophy of the second metatarsal and mobility of the first
      ray, the length of the first metatarsal, pes planus, or restricted ankle
      dorsiflexion. No correlation was found between mobility of the first ray and
      either pes planus or restricted ankle dorsiflexion. A weak correlation (r = 0.4)
      was noted between increased mobility of the first ray and the hallux valgus
      angle. CONCLUSIONS: Our findings do not support Morton's concept that medial
      cortical hypertrophy and increased shaft width of the second metatarsal are
      associated with increased mobility of the first ray or relative shortness of the
      first metatarsal. In addition, hypertrophy of the second metatarsal was not
      associated with either pes planus or restricted ankle dorsiflexion. We found the
      practice of using hypertrophy of the second metatarsal as an indicator of
      mobility of the first ray to be unreliable, and thus we consider it to be an
      inappropriate indication for arthrodesis of the first metatarsocuneiform joint in
      the treatment of hallux valgus deformity.

PMID- 15252084
TI  - Idiopathic arm pain.
AB  - BACKGROUND: Arm pain with little or no objective abnormality (referred to herein
      as idiopathic arm pain) is a common and frustrating problem for both patients and
      physicians. We investigated the relative effect of idiopathic arm pain and arm
      pain due to a discrete diagnosis on upper-extremity-specific health status.
      METHODS: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was
      completed by 3888 patients seen over a twelve-month period. Scores for the entire
      sample, for 496 patients diagnosed with idiopathic arm pain, and for 1379
      patients diagnosed with one of twenty-one discrete conditions were compared.
      RESULTS: Patients with idiopathic pain reported substantial and highly variable
      upper-limb-specific dysfunction (average DASH score [and standard deviation], 36
      +/- 24 points). Patients with discrete diagnoses also exhibited substantial
      variation (average standard deviation, 25; range, 6 to 27) as well as long right
      tails indicating floor effects, particularly for less severe conditions (Pearson
      correlation of r = -0.87 between the mean DASH score and skewness). Analysis of
      variance confirmed the ability of the DASH instrument to discriminate among
      groups of diagnoses of varying severity, but post hoc Tukey analysis identified
      ten subgroups with substantial overlap of the DASH scores. CONCLUSIONS: Patients
      with idiopathic arm pain report substantial and highly variable upper-extremity
      dysfunction. The wide variations observed in the DASH scores of the patients with
      idiopathic pain and those with discrete diagnoses are greater than would be
      expected on the basis of the variations in the objective pathological conditions
      and may reflect the strong influence of psychological and sociological factors on
      health status measures.

PMID- 15252085
TI  - Meniscal transplantation in symptomatic patients less than fifty years old.
AB  - BACKGROUND: The purpose of this study was to prospectively evaluate the results
      of meniscal transplantation in a consecutive series of younger patients treated
      for pain in the tibiofemoral compartment following a previous meniscectomy.
      METHODS: Forty cryopreserved menisci were implanted into thirty-eight patients.
      Sixteen knees also had an osteochondral autograft transfer, and nine had a knee
      ligament reconstruction. The clinical outcome and failure rate of all transplants
      were evaluated at a mean of forty months postoperatively. Meniscal allograft
      characteristics were determined with use of a rating system that combined
      subjective, clinical, and magnetic resonance imaging factors. RESULTS: Thirty
      four (89%) of the thirty-eight patients rated the knee condition as improved.
      Before surgery, thirty patients (79%) had pain with daily activities, but only
      four (11%) had such pain at the time of the latest follow-up. While noteworthy
      pain was present in the tibiofemoral compartment in all forty knees before
      surgery, twenty-seven knees (68%) had no pain and thirteen (33%) had only mild
      compartment pain at the time of the latest follow-up. Twenty-nine patients (76%)
      returned to light low-impact sports without problems. Concomitant osteochondral
      autograft transfer and knee ligament reconstruction procedures improved knee
      function and did not increase the rate of complications. Meniscal allograft
      characteristics were normal in seventeen knees (43%), altered in twelve (30%),
      and failed in eleven (28%). CONCLUSIONS: The short-term results of meniscal
      transplantation are encouraging in terms of reducing knee pain and increasing
      function; however, long-term transplant function and any chondroprotective
      effects remain unknown and require further investigation.

PMID- 15252086
TI  - Management of peripheral nerve defects: external fixator-assisted primary
      neurorrhaphy.
AB  - BACKGROUND: Controlled joint extension followed by gradual distraction with use
      of an external fixator may facilitate primary repair of peripheral nerve defects
      by permitting end-to-end repair without tension. The hypothesis of the present
      study was that gradual lengthening of nerve repairs with use of incremental
      distraction would provide superior results compared with grafting or repair under
      tension. METHODS: A median nerve segment measuring four times the diameter of the
      nerve was resected in thirty-six rabbits to create a 7-mm gap in the nerve.
      Neurorrhaphy was performed with use of one of three techniques. In Group 1 (cable
      graft), a tension-free medial antebrachial cutaneous graft was placed to allow
      full range of motion of the elbow postoperatively. In Group 2 (end-to-end repair
      without distraction), the elbow was externally fixed in hyperflexion and the
      nerve was repaired end-to-end. At fourteen days, the fixator was removed and
      unprotected elbow motion was permitted. In Group 3 (end-to-end repair with
      gradual distraction), the elbow was externally fixed in hyperflexion and primary
      neurorrhaphy was performed. At fourteen days, the elbow was extended 10 degrees
      every other day with use of the articulated external fixator until full extension
      was achieved. Median nerve amplitude, latency, and nerve-conduction velocity;
      flexor digitorum superficialis single-twitch force generation and maximum tetanic
      force generation; muscle mass; and elbow range of motion were measured at three
      or six months. In addition, histologic analysis of the median nerve distal to the
      repair site and the morphometry of the neuromuscular junction in the flexor
      digitorum superficialis were performed at six months. RESULTS: All rabbits
      regained full active and passive range of motion. At three months, the nerve
      conduction velocities in Groups 2 and 3 were significantly greater than that in
      Group 1. At six months, the nerve-conduction velocities and amplitudes in Group 3
      were significantly greater than those in Groups 1 and 2. At six months, the
      tetanic force in Group 3 was significantly greater than those in Groups 1 and 2.
      There were no significant differences in muscle mass among the groups. There were
      no significant differences in histological findings among the three groups,
      although there was a trend toward larger fiber size in Group 3 as compared with
      the other two groups. The neuromuscular junctions in Group 3 had a significantly
      larger surface area than did those in Group 1 (p = 0.002) and Group 2 (p =
      0.034). CONCLUSION: The use of an articulated external fixator and controlled
      gradual distraction appears to facilitate the treatment of peripheral nerve
      defects.

PMID- 15252087
TI  - Atrophy of the deltoid muscle following rotator cuff surgery.
AB  - BACKGROUND: Less invasive procedures have recently been introduced to facilitate
      an earlier return to sports or work activities after rotator cuff repair. Few
      reports, however, have verified whether such procedures are really less invasive
      than conventional open repair. The purpose of this study was to compare the
      postoperative thickness of the deltoid muscle in patients treated with either
      conventional or mini-open rotator cuff repair. METHODS: Conventional open repair
      was performed from 1994 through 1997 in forty-three patients with rotator cuff
      tears. The mini-open deltoid-splitting approach was introduced in 1997, and the
      cases of thirty-five patients who underwent that procedure were reviewed. The two
      groups were compared with respect to the thickness of the anterior fibers of the
      deltoid muscle measured on the transverse magnetic resonance images, the degree
      of active forward flexion, and the times required for return to work and sports
      activities. RESULTS: The thickness of the anterior deltoid fibers did not change
      significantly after surgery in the mini-open repair group, whereas it was
      significantly decreased in the open repair group at six months as well as at
      twelve months postoperatively (p < 0.05). At three months postoperatively, the
      mean University of California at Los Angeles score for active forward flexion in
      the patients treated with the mini-open repair (4.9 points) was significantly
      greater than that in the patients in the conventional open repair group (4.6
      points) (p < 0.05). In addition, the mean time-period required for return to work
      in the mini-open repair group (2.4 months) was significantly shorter than that
      required in the control group (3.4 months) (p < 0.05). CONCLUSIONS: The mini-open
      repair appeared to cause less postoperative atrophy of the deltoid muscle than
      did the conventional open rotator cuff repair, and patients treated with the mini
      open repair recovered more quickly.

PMID- 15252088
TI  - Predictors of paralysis in the rheumatoid cervical spine in patients undergoing
      total joint arthroplasty.
AB  - BACKGROUND: Rheumatoid arthritis is sometimes associated with radiographic
      evidence of instability of the cervical spine, most commonly an abnormal
      subluxation between vertebrae. When this instability compromises the space that
      is available for the spinal cord, it may be predictive of paralysis. However, the
      prevalence of radiographic signs of instability that are predictive of paralysis
      among patients with nonspinal orthopaedic manifestations of rheumatoid arthritis
      is unknown. METHODS: Radiographs of the cervical spine of patients with
      rheumatoid arthritis who had undergone total joint arthroplasty over a five-year
      period were retrospectively reviewed. The radiographs were evaluated for
      predictors of paralysis (a posterior atlantodental interval of <14 mm or a
      subaxial space available for the cord measuring <14 mm) and were compared with
      traditional parameters of instability (an anterior atlantodental interval of >3
      mm or subaxial subluxation of >3 mm). RESULTS: Forty-nine of the sixty-five
      patients who were identified had flexion and extension lateral radiographs
      available for review. Only one of these patients had a posterior atlantodental
      interval of <14 mm, and only three had a space available for the cord that
      measured <14 mm at one level or more. In comparison, twenty patients had
      radiographic evidence of instability on the basis of traditional parameters.
      CONCLUSIONS: Although nearly one-half of the patients in the present study had
      radiographic evidence of cervical instability on the basis of traditional
      measurements, only four patients (8%) had a radiographic finding that was
      predictive of paralysis. Thus, while radiographic evidence of cervical
      instability was not infrequent in this population of patients who underwent total
      joint arthroplasty for rheumatoid arthritis, radiographic predictors of paralysis
      were much less common.

PMID- 15252089
TI  - Percutaneous injection of recombinant human bone morphogenetic protein-2 in a
      calcium phosphate paste accelerates healing of a canine tibial osteotomy.
AB  - BACKGROUND: In this study, we evaluated the capacity of a single percutaneous
      injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered
      in a rapidly resorbable calcium phosphate paste (alpha-BSM) to accelerate bone
      healing in a canine tibial osteotomy model. We hypothesized that the osteotomy
      sites would heal faster after percutaneous delivery of rhBMP-2/alpha-BSM than
      they would after injection of alpha-BSM alone or after no treatment. METHODS:
      Bilateral tibial osteotomy was performed and the sites were stabilized with
      external fixators in sixteen dogs. Four hours after the surgery, one limb of each
      dog was treated with a single percutaneous injection of rhBMP-2/alpha-BSM paste
      or an equal volume of alpha-BSM alone. There were eight limbs in each group, and
      the osteotomy site in the contralateral limb served as an untreated control. The
      results were evaluated with serial radiography and force-plate analysis at four
      and eight weeks after surgery and with mechanical testing and histologic
      examination at eight weeks after the surgery. RESULTS: At four and eight weeks
      after the osteotomy and treatment, the scores for radiographic union were
      significantly greater for the rhBMP-2/alpha-BSM-treated limbs than they were for
      the alpha-BSM-treated or untreated, control limbs (p < 0.05). The callus area in
      the rhBMP-2/alpha-BSM-treated limbs was significantly greater than that in the
      alpha-BSM-treated and untreated, control limbs at four and eight weeks
      postinjection (p < 0.05). The time-integrated vertical force for the rhBMP-2
      treated limbs was significantly greater than that for their contralateral
      controls at four weeks and significantly greater than that for the treated and
      control limbs of the alpha-BSM-treated dogs at four and eight weeks after the
      surgery (p </= 0.05). The rhBMP-2-treated limbs were significantly stiffer in
      bending and in torsion (p < 0.05) compared with the alpha-BSM-treated and control
      limbs. Histologic analysis demonstrated increased bone formation and more mature
      bone at the osteotomy site in the rhBMP-2-treated limbs compared with that in the
      alpha-BSM-treated and control limbs. CONCLUSIONS: This study demonstrates the
      capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable
      calcium phosphate paste (alpha-BSM) four hours after surgery to accelerate the
      healing of tibial osteotomy sites in a canine model.

PMID- 15252090
TI  - Chiari pelvic osteotomy for advanced osteoarthritis in patients with hip
      dysplasia.
AB  - BACKGROUND: It is not clear whether a Chiari pelvic osteotomy performed for the
      treatment of advanced osteoarthritis can delay the need for total hip
      arthroplasty. We present the mid-term results of the Chiari pelvic osteotomy
      performed for the treatment of Tonnis grade-3 osteoarthritis (large cysts, severe
      narrowing of the joint space, or severe deformity or necrosis of the head with
      extensive osteophyte formation), with a particular focus on whether this
      procedure can delay the need for total hip arthroplasty. METHODS: We followed
      thirty-two hips in thirty-one patients with Tonnis grade-3 osteoarthritis who had
      refused total hip arthroplasty and had been treated with a Chiari pelvic
      osteotomy. The mean age at the time of surgery was 35.2 years. The mean duration
      of follow-up was 11.2 years, at which time clinical evaluation with the Harris
      hip score and radiographic evaluation were performed. RESULTS: The average Harris
      hip score improved from 52 points preoperatively to 77 points at the time of
      follow-up; the average pain score improved from 20 to 31 points. Three hips with
      a hip score of <70 points required total hip arthroplasty. With a hip score of
      <70 points as the end point, the cumulative rate of survival at ten years was
      72%. The clinical outcome was significantly influenced by the preoperative center
      edge angle (p = 0.004), the preoperative acetabular head index (p = 0.039),
      achievement of the appropriate osteotomy level (p = 0.011), and superior
      migration (p = 0.009) and lateral migration (p = 0.026) of the femoral head.
      CONCLUSIONS: Although the clinical results were inferior to those of total hip
      arthroplasty, Chiari pelvic osteotomy may be an option for young patients with
      advanced osteoarthritis who prefer a joint-conserving procedure to total hip
      arthroplasty and accept a clinical outcome that is predicted to be less optimal
      than that of total hip arthroplasty. Moderate dysplasia and moderate subluxation
      without complete obliteration of the joint space and a preoperative center-edge
      angle of at least -10 degrees are desirable selection criteria.

PMID- 15252091
TI  - Preoperative factors associated with improvements in shoulder function after
      humeral hemiarthroplasty.
AB  - BACKGROUND: The relationship between the characteristics of the shoulder that can
      be determined before humeral hemiarthroplasty and the functional improvement
      after surgery is not known. The goal of this study was to test the hypothesis
      that the functional outcome of this procedure correlated significantly with
      factors that are identifiable preoperatively. METHODS: The study group included
      seventy-one shoulders in sixty-eight patients undergoing hemiarthroplasty,
      performed by the same surgeon, for diagnoses other than acute fracture. The mean
      age of the patients was sixty-one years (range, thirty to eighty-three years).
      The results were characterized in terms of the change in self-assessed shoulder
      function and general health status at an average of forty-nine months (range,
      twenty-four to 142 months) after surgery. RESULTS: The preoperative absence of
      erosion of the glenoid was associated with greater improvement in shoulder
      function and level of comfort after hemiarthroplasty (p < 0.001). Shoulders that
      had not had previous surgery had greater functional improvement than did those
      that had previous surgery (p = 0.012). Shoulders with an intact rotator cuff
      showed significantly (p < 0.5) greater improvement in the ability to lift weight
      above shoulder level after hemiarthroplasty (p <0.5). With regard to diagnoses,
      shoulders with rheumatoid arthritis, capsulorrhaphy arthropathy, and cuff tear
      arthropathy had the least functional improvement, whereas those with
      osteonecrosis (p = 0.0004) and with primary (p = 0.02) and secondary degenerative
      joint disease (p = 0.03) had the greatest improvement. Patient age and gender did
      not significantly affect the outcome. CONCLUSIONS: These results suggest that the
      functional improvement following humeral hemiarthroplasty is related to factors
      that are identifiable before surgery. These data may be of benefit in
      preoperative discussions with patients who have a shoulder disorder and are
      considering treatment with hemiarthroplasty.

PMID- 15252092
TI  - Osteoarthritis in the carpometacarpal joint of the thumb. Prevalence and
      associations with disability and mortality.
AB  - BACKGROUND: This study was designed to investigate the prevalence of
      osteoarthritis in the carpometacarpal joint of the thumb in adults thirty years
      of age or older in Finland. METHODS: Between 1978 and 1980, a representative
      population sample of 8000 Finns thirty years of age or older were invited to have
      a comprehensive health examination; 90% accepted. Hand radiographs were made of
      3595 subjects. Since the examination, the subjects have been followed
      systematically to assess work disability and mortality by reviewing registers
      covering the whole population. RESULTS: The age-adjusted prevalence of thumb
      carpometacarpal osteoarthritis of Kellgren grade 2, 3, or 4 was 7% for men and
      15% for women. After adjustment for age, sex, and other alleged risk factors,
      body mass index was found to be directly proportional to the prevalence of thumb
      carpometacarpal osteoarthritis in both sexes. The adjusted odds ratio was 1.29
      (95% confidence interval, 1.15 to 1.43) per 5-kg/m(2) increment in body mass
      index. No significant association was found between the physical workload history
      and thumb carpometacarpal osteoarthritis. Restricted mobility of the thumb and
      local tenderness and swelling were frequently found in conjunction with
      radiographic evidence of thumb carpometacarpal osteoarthritis. Advanced (grade-3
      or 4) thumb carpometacarpal osteoarthritis predicted the total mortality rate in
      men (adjusted relative risk, 1.32; 95% confidence interval, 1.03 to 1.69).
      Radiographic signs of thumb carpometacarpal osteoarthritis did not predict work
      disability. CONCLUSIONS: and CLINICAL RELEVANCE: Obesity is a strong determinant
      of thumb carpometacarpal osteoarthritis in both sexes. The effect of thumb
      carpometacarpal osteoarthritis on disability and mortality in the general
      population is modest. Because of the rarity of ensuing disability,
      carpometacarpal osteoarthritis of the thumb is likely to be underdiagnosed in
      clinical practice.

PMID- 15252093
TI  - A histological and immunohistochemical study of the subsynovial connective tissue
      in idiopathic carpal tunnel syndrome.
AB  - BACKGROUND: The most common histological finding in carpal tunnel syndrome is
      noninflammatory synovial fibrosis. The accumulated effect of minor injuries is
      believed to be an important etiologic factor in some cases of carpal tunnel
      syndrome. We sought evidence of such injuries in the synovial tissue of patients
      with carpal tunnel syndrome and in cadaver controls. METHODS: We compared
      synovial specimens from thirty patients who had idiopathic carpal tunnel syndrome
      with specimens from a control group of ten fresh-frozen cadavers of individuals
      who had not had an antemortem diagnosis of carpal tunnel syndrome and who met the
      same exclusion criteria. Analysis included histological and immunohistochemical
      examination for the distribution of collagen types I, II, III, and VI and
      transforming growth factor-beta (TGF-beta) RI, RII, and RIII. RESULTS:
      Histological examination showed a marked increase in fibroblast density, collagen
      fiber size, and vascular proliferation in the specimens from the patients
      compared with the control specimens (p < 0.001). Collagen types I and II were not
      found in the synovium of either the patients or the controls, but collagen type
      VI was a major component of both. Collagen type-III fibers were more abundant in
      the patients than in the controls (p < 0.001). Expression of TGF-beta RI was
      found in the endothelial cells and fibroblasts in the patient and control
      specimens, with a marked increase in expression in the fibroblasts of the
      patients compared with that in the control tissue (p < 0.001). CONCLUSIONS: These
      findings are similar to those after injury to skin, tendon, and ligament and
      suggest that patients with idiopathic carpal tunnel syndrome may have sustained
      an injury to the subsynovial connective tissue.

PMID- 15252094
TI  - The natural history of cervical disc calcification in children.
AB  - BACKGROUND: Calcification of cervical intervertebral discs is uncommon in
      children. The cases of approximately 200 children have been reported in the
      literature. The objective of the present study was to examine the natural history
      of this condition. METHODS: Seventeen consecutive children, ten boys and seven
      girls, with calcified cervical intervertebral discs were included in the study.
      The mean age at diagnosis was 7.7 years. Three children had had a fever, and two
      had a history of trauma. All of the children complained of neck pain except one
      who was asymptomatic and was identified by chance. On radiographs, the
      calcification was seen within the central part of the cervical intervertebral
      discs. All children had treatment of the symptoms, and they were then followed
      periodically until the disappearance of both the symptoms and the calcific
      deposits. RESULTS: The children were followed for a mean of five years, and all
      had a complete disappearance of both the symptoms and the calcification. None had
      recurrent symptoms or calcifications. The average time to resolution of the
      symptoms and the calcifications was 34.3 days (range, seventeen to 173 days) and
      fifteen months (range, three to sixty months), respectively. With the numbers
      available, factors such as age, level of disc calcification, severity of
      symptoms, and degree of spinal canal compromise were not related to the time of
      resolution. CONCLUSIONS: Cervical disc calcification in children is a self
      limiting condition with an excellent prognosis. Even if clinical symptoms due to
      nerve-root or spinal cord compression are present, conservative therapy produces
      satisfactory results. Therefore, nerve-root or spinal cord compression by a
      calcified cervical disc should not be considered an absolute indication for
      surgical intervention.

PMID- 15252095
TI  - The efficacy of ultrasound in the evaluation of dynamic scapholunate ligamentous
      instability.
AB  - BACKGROUND: The accuracy of diagnostic imaging modalities that are currently used
      to evaluate dynamic scapholunate ligamentous instability is equivocal. Ultrasound
      is commonly used for a wide variety of diagnostic purposes in orthopaedics. The
      purpose of the present study was to determine the efficacy of ultrasound in the
      diagnosis of dynamic scapholunate ligamentous instability. METHODS: Two groups of
      individuals were prospectively studied. Group A included patients with a clinical
      diagnosis of unilateral dynamic scapholunate ligamentous instability, and Group B
      included asymptomatic volunteer control subjects. Dynamic ultrasound examinations
      of the dorsal portion of the scapholunate ligament in both wrists of all
      individuals were performed by radiologists. The radiologists were blinded with
      regard to the group to which each person belonged as well as with regard to the
      affected wrist in the patients in Group A. Arthroscopic examinations of the
      affected wrist in all of the patients in Group A were then performed by surgeons
      who were blinded with regard to the results of the ultrasound examination, and
      the results of the arthroscopic and ultrasound examinations were compared. The
      ability of ultrasound to discern asymptomatic from symptomatic individuals was
      also determined. RESULTS: Over a period of 1.5 years, a total of sixty-four
      wrists were evaluated in fourteen patients (Group A) and eighteen normal subjects
      (Group B). All fourteen nonaffected wrists in Group A and all thirty-six wrists
      in Group B were correctly identified as normal with use of ultrasound. Of the
      fourteen affected wrists in Group A, thirteen were found to have scapholunate
      ligament laxity on the basis of arthroscopy (twelve wrists) or arthrotomy (one
      wrist); six of these thirteen wrists had been correctly identified as abnormal
      with use of ultrasound (a true-positive result), and seven had false-negative
      results. There was one true-negative result. The ability of ultrasound to
      differentiate between normal and abnormal wrists was significant (p < 0.001). For
      the sixty-four wrists, statistical analysis revealed that ultrasound had a
      sensitivity of 46.2%, a specificity of 100%, and an accuracy of 89.1%.
      CONCLUSIONS: We conclude that ultrasound has a high specificity and accuracy but
      a low sensitivity for the evaluation of dynamic scapholunate ligamentous
      instability, and we recommend its use as an adjunct to other diagnostic
      modalities for this purpose.

PMID- 15252096
TI  - Stiffness after total knee arthroplasty. Prevalence of the complication and
      outcomes of revision.
AB  - BACKGROUND: Stiffness is an uncommon but disabling problem after total knee
      arthroplasty. The prevalence of stiffness after knee replacement has not been
      well defined in the literature. In addition, the outcomes of revision surgery for
      a stiff knee following arthroplasty have not been evaluated in a large series of
      patients, to our knowledge. The purposes of this study were to define the
      prevalence of stiffness after primary total knee arthroplasty and to evaluate the
      efficacy of revision surgery for treatment of the stiffness. METHODS: We defined
      a stiff knee as one having a flexion contracture of >/=15 degrees and/or <75
      degrees of flexion. Two separate groups were evaluated. First, the results of
      1000 consecutive primary total knee replacements were reviewed to determine the
      prevalence of stiffness. Second, the results of fifty-six revisions performed
      because of stiffness, sometimes associated with pain or component loosening,
      after primary total knee arthroplasty were evaluated. RESULTS: The prevalence of
      stiffness was 1.3%, at an average of thirty-two months postoperatively. The
      patients with a stiff knee had had significantly less preoperative extension and
      flexion than did those without a stiff knee (p < 0.0001). There were no
      significant differences in age, gender, implant design, diagnosis, or the need
      for lateral release between the patients with and without stiffness. The second
      cohort, of knees revised because of stiffness, were followed for an average of
      forty-three months. The mean Knee Society score improved from 38.5 points
      preoperatively to 86.7 points at the time of follow-up; the mean Knee Society
      function score, from 40.0 to 58.4 points; and the mean Knee Society pain score,
      from 15.0 to 46.9 points. The mean flexion contracture decreased from 11.3
      degrees to 3.2 degrees, the mean flexion improved from 65.8 degrees to 85.4
      degrees, and the mean arc of motion improved from 54.6 degrees to 82.2 degrees.
      The arc of motion improved in 93% of the knees, and flexion increased in 80%.
      Extension improved in 63%, and it remained unchanged in 30%. CONCLUSIONS: The
      prevalence of stiffness in our series of 1000 primary knee arthroplasties was
      1.3%. Revision surgery was a satisfactory treatment option for stiffness, as the
      Knee Society scores improved, the flexion contractures diminished, and 93% of the
      knees had an increased arc of motion. However, the results suggest that the
      benefits are modest.

PMID- 15252097
TI  - Transfer of fascicles from the ulnar nerve to the nerve to the biceps in the
      treatment of upper brachial plexus palsy.
AB  - BACKGROUND: The transfer of one or more ulnar nerve fascicles to the nerve to the
      biceps can restore elbow flexion in patients with upper brachial plexus palsy.
      The purposes of the present retrospective study were to evaluate the results of
      this procedure, to measure the delay in reinnervation of the biceps muscle, and
      to define the indications for a secondary Steindler flexorplasty. METHODS: Thirty
      two patients with an upper nerve-root brachial plexus injury were reviewed at an
      average of thirty-one months after the nerve fascicle transfer. The average age
      of the patients was twenty-eight years. The average time between the injury and
      the operation was nine months. Patients were evaluated with regard to
      reinnervation of the biceps, ulnar nerve function, elbow flexion strength, and
      grip strength. RESULTS: The average time required for reinnervation of the biceps
      after nerve fascicle transfer was five months. No motor or sensory deficits
      related to the ulnar nerve were noted clinically. The average grip strength at
      the time of the last follow-up was 25 kg (an improvement of 9 kg compared with
      the preoperative value). After the nerve transfer, twenty-four patients achieved
      grade-3 elbow flexion strength or better according to the grading system of the
      Medical Research Council. A Steindler flexorplasty was performed as a secondary
      procedure in ten patients with persistent grade-3 flexor strength or worse. In
      eight of these cases, elbow flexion strength improved after nerve transfer and
      flexorplasty. Overall, thirty of the thirty-two patients achieved a good result
      (grade-4 strength) or a fair result (grade-3 strength). CONCLUSIONS: We recommend
      this procedure for brachial plexus injuries involving the C5-C6 or C5-C6-C7 nerve
      roots. This procedure spares the C5 nerve root and other nerves for grafting or
      transfer elsewhere. A secondary Steindler flexorplasty is indicated for patients
      who have persistent grade-3 elbow flexion strength or worse for at least twelve
      months after nerve fascicle transfer.

PMID- 15252098
TI  - Inferior subluxation of the fibular head following tibial lengthening with a
      unilateral external fixator.
AB  - BACKGROUND: Inferior subluxation of the proximal part of the fibula has been
      reported to occur with distraction osteogenesis of the tibia; however, the
      clinical sequelae of this subluxation are unknown. The purpose of this study was
      to evaluate inferior subluxation of the proximal part of the fibula and its
      possible clinical implications in patients who had undergone tibial lengthening
      by distraction osteogenesis with use of a unilateral external fixator. METHODS:
      Thirty tibiae in seventeen patients with a variety of conditions underwent tibial
      lengthening by distraction osteogenesis with use of a unilateral external fixator
      and were followed clinically and radiographically for a mean of two years and ten
      months (range, two to four years). Ten patients were female and seven were male.
      Their mean age at the time of the surgery was seventeen years (range, eight to
      twenty-five years). The mean tibial lengthening was 8.1 cm (range, 3.5 to 13 cm).
      RESULTS: An inferior shift of the fibular head in relation to the tibia was
      evident in all cases. The shift, which ranged from 0.4 to 3.3 cm, was
      proportionally related to the amount of tibial lengthening. This type of
      subluxation is probably attributable to the tension that is exerted by the intact
      interosseous membrane during the distraction as well as to the tension of the
      regenerated bone of the fibula and the fact that the fibula itself is not fixed
      or directly lengthened by the external fixator. CONCLUSIONS: It appears that
      inferior subluxation of the fibula is a common phenomenon in patients undergoing
      tibial lengthening by distraction osteogenesis with use of a unilateral external
      fixator. However, no clinical symptoms or findings related to the inferior
      subluxation of the fibula were found in our series.

PMID- 15252099
TI  - Adjacent segment degeneration in the lumbar spine.
AB  - BACKGROUND: A primary concern after posterior lumbar spine arthrodesis is the
      potential for adjacent segment degeneration cephalad or caudad to the fusion
      segment. There is controversy regarding the subsequent degeneration of adjacent
      segments, and we are aware of no long-term studies that have analyzed both
      cephalad and caudad degeneration following posterior arthrodesis. A retrospective
      investigation was performed to determine the rates of degeneration and survival
      of the motion segments adjacent to the site of a posterior lumbar fusion.
      METHODS: Two hundred and fifteen patients who had undergone posterior lumbar
      arthrodesis were included in this study. The study group included 126 female
      patients and eighty-nine male patients. The average duration of follow-up was 6.7
      years. Radiographs were analyzed with regard to arthritic degeneration at the
      adjacent levels both preoperatively and at the time of the last follow-up visit.
      Disc spaces were graded on a 4-point arthritic degeneration scale. Correlation
      analysis was used to determine the contribution of independent variables to the
      rate of degeneration. Survivorship analysis was performed to describe the
      degeneration of the adjacent motion segments. RESULTS: Fifty-nine (27.4%) of the
      215 patients had evidence of degeneration at the adjacent levels and elected to
      have an additional decompression (fifteen patients) or arthrodesis (forty-four
      patients). Kaplan-Meier analysis predicted a disease-free survival rate of 83.5%
      (95% confidence interval, 77.5% to 89.5%) at five years and of 63.9% (95%
      confidence interval, 54.0% to 73.8%) at ten years after the index operation.
      Although there was a trend toward progression of the arthritic grade at the
      adjacent disc levels, there was no significant correlation, with the numbers
      available, between the preoperative arthritic grade and the need for additional
      surgery. CONCLUSIONS: The rate of symptomatic degeneration at an adjacent segment
      warranting either decompression or arthrodesis was predicted to be 16.5% at five
      years and 36.1% at ten years. There appeared to be no correlation with the length
      of fusion or the preoperative arthritic degeneration of the adjacent segment.

PMID- 15252100
TI  - Vascularized proximal fibular epiphyseal transfer for distal radial
      reconstruction.
AB  - BACKGROUND: Treatment of the loss of the distal part of the radius, including the
      physis and epiphysis, in a skeletally immature patient requires both replacement
      of the osseous defect and restoration of longitudinal growth. Autologous
      vascularized epiphyseal transfer is the only possible procedure that can meet
      both requirements. METHODS: Between 1993 and 2002, six patients with a mean age
      of 8.4 years (range, six to eleven years) who had a malignant bone tumor in the
      distal part of the radius underwent microsurgical reconstruction of the distal
      part of the radius with a vascularized proximal fibular transfer, including the
      physis and a variable length of the diaphysis. All of the grafts were supplied by
      the anterior tibial vascular network. The rate of survival and bone union of the
      graft, the growth rate per year, the ratio between the lengths of the ulna and
      the reconstructed radius, and the range of motion of the wrist were evaluated for
      five of the six patients who had been followed for three years or more. RESULTS:
      The mean duration of follow-up of the six patients was 4.4 years (range, eight
      months to nine years). All six transfers survived and united with the host bone
      within two months postoperatively. The five patients who were followed for three
      years or more had consistent and predictable longitudinal growth. Serial
      radiographs revealed remodeling of the articular surface. The functional result
      was rated as excellent for all but one patient, in whom the distal part of the
      ulna had also been resected because of neoplastic involvement. No major
      complication occurred at the recipient site, whereas a peroneal nerve palsy
      occurred at the donor site in three patients. The palsy was transient in two
      patients, but it persisted in one. No instability of the knee joint was observed.
      CONCLUSIONS: After radical resection of the distal part of the radius because of
      a neoplasm in children, vascularized proximal fibular transfer, based on the
      anterior tibial artery, permits a one-stage skeletal and joint reconstruction,
      provides excellent function, and minimizes the discrepancy between the distal
      radial and ulnar lengths.

PMID- 15252101
TI  - A blood-conservation algorithm to reduce blood transfusions after total hip and
      knee arthroplasty.
AB  - BACKGROUND: Donation of autologous blood before total joint arthroplasty is
      inconvenient and costly, causes a phlebotomy-induced anemia, and may be wasteful
      and unnecessary for the nonanemic patient. We developed a blood-conservation
      algorithm that does not require predonation of autologous blood, employs
      selective use of epoetin alfa, and uses evidence-based transfusion criteria. Our
      hypothesis was that use of this algorithm would reduce the rate of transfusion
      after unilateral total hip and knee arthroplasty as compared with the rates
      described in previous reports. METHODS: We retrospectively reviewed the records
      of 500 consecutive patients in whom unilateral primary total hip or knee
      arthroplasty had been performed by a single surgeon. The same blood-conservation
      algorithm was recommended to all patients. Two groups of patients were
      identified: the first group consisted of 433 patients in whom the algorithm was
      followed, and the second group consisted of sixty-seven patients in whom the
      algorithm was not followed. RESULTS: In the group in which the algorithm was
      followed, the rates of allogeneic transfusion after total knee and total hip
      arthroplasty were 1.4% (three of 220) and 2.8% (six of 213), respectively. The
      overall rate of transfusion in this group was only 2.1% (nine of 433). The
      prevalence of transfusion in the group in which the algorithm was not followed
      was 16.4% (eleven of sixty-seven). This difference was significant (p = 0.0001).
      CONCLUSIONS: The use of this blood-conservation algorithm resulted in a
      significant reduction in the need for allogeneic blood transfusions after
      unilateral total hip and knee arthroplasty, and the results compare favorably
      with the rates of transfusion described in previous reports.

PMID- 15252102
TI  - Simultaneous bilateral rupture of the pectoralis major tendon. A case report.

PMID- 15252103
TI  - Dissociation of an ultra-high molecular weight polyethylene insert from the
      tibial baseplate after total knee arthroplasty. A case report.

PMID- 15252104
TI  - Spontaneous lumbar hernia. A case report.

PMID- 15252105
TI  - Surgical treatment of acute elbow flexion contracture in patients with congenital
      proximal radioulnar synostosis. A report of two cases.

PMID- 15252106
TI  - Pseudopathologic fracture of the neck of the femur. A case report.

PMID- 15252107
TI  - Progressive peroneal nerve palsy in a varus arthritic knee. A case report.

PMID- 15252108
TI  - Engineering principles of clinical cell-based tissue engineering.
AB  - Tissue engineering is a rapidly evolving discipline that seeks to repair,
      replace, or regenerate specific tissues or organs by translating fundamental
      knowledge in physics, chemistry, and biology into practical and effective
      materials, devices, systems, and clinical strategies. Stem cells and progenitors
      that are capable of forming new tissue with one or more connective tissue
      phenotypes are available from many adult tissues and are defined as connective
      tissue progenitors. There are four major cell-based tissue-engineering
      strategies: (1) targeting local connective tissue progenitors where new tissue is
      desired, (2) transplanting autogenous connective tissue progenitors, (3)
      transplanting culture-expanded or modified connective tissue progenitors, and (4)
      transplanting fully formed tissue generated in vitro or in vivo. Stem cell
      function is controlled by changes in stem cell activation and self-renewal or by
      changes in the proliferation, migration, differentiation, or survival of the
      progeny of stem cell activation, the downstream progenitor cells. Three
      dimensional porous scaffolds promote new tissue formation by providing a surface
      and void volume that promotes the attachment, migration, proliferation, and
      desired differentiation of connective tissue progenitors throughout the region
      where new tissue is needed. Critical variables in scaffold design and function
      include the bulk material or materials from which it is made, the three
      dimensional architecture, the surface chemistry, the mechanical properties, the
      initial environment in the area of the scaffold, and the late scaffold
      environment, which is often determined by degradation characteristics. Local
      presentation or delivery of bioactive molecules can change the function of
      connective tissue progenitors (activation, proliferation, migration,
      differentiation, or survival) in a manner that results in new or enhanced local
      tissue formation. All cells require access to substrate molecules (oxygen,
      glucose, and amino acids). A balance between consumption and local delivery of
      these substrates is needed if cells are to survive. Transplanted cells are
      particularly vulnerable. Theoretical calculations can be used to explore the
      relationships among cell density, diffusion distance, and cell viability within a
      graft and to design improved strategies for transplantation of connective tissue
      progenitors. Rational strategies for tissue engineering seek to optimize new
      tissue formation through the logical selection of conditions that modulate the
      performance of connective tissue progenitors in a graft site to produce a desired
      tissue. This increasingly involves strategies that combine cells, matrices,
      inductive stimuli, and techniques that enhance the survival and performance of
      local or transplanted connective tissue progenitors.

PMID- 15252110
TI  - Knowledge is our business.

PMID- 15252111
TI  - Stress and coping among orthopaedic surgery residents and faculty.
AB  - BACKGROUND: Evaluations of physicians and residents have revealed concerning
      levels of psychosocial dysfunction. The purposes of this study were to determine
      the quality of life of orthopaedic residents and faculty and to identify the risk
      factors for decompensation. METHODS: Twenty-one orthopaedic residents and twenty
      five full-time orthopaedic faculty completed a 102-question voluntary, anonymous
      survey. The survey consisted of three validated instruments, i.e., the Maslach
      Burnout Inventory, the General Health Questionnaire-12, and the Revised Dyadic
      Adjustment Scale; and three novel question sets addressing background and
      demographic information, stress reaction and management, and the balance between
      work and home life. Descriptive statistics, pairwise correlations, simple t
      tests, and Pearson and nonparametric Spearman correlations were calculated. The
      simple correlation coefficient was used to assess bivariate relationships.
      RESULTS: The mean overall quality-of-life score, on a scale of 0 to 4 points, was
      2.5 points for residents compared with 3.6 points for faculty members. Residents
      reported considerable burnout, showing a high level of emotional exhaustion and
      depersonalization and an average level of personal achievement, whereas faculty
      reported minimal burnout, showing a low level of emotional exhaustion (p <
      0.0003), an average level of depersonalization (p < 0.0001), and a high level of
      personal achievement (p < 0.0001). Only two of twenty-five faculty members
      (compared with seven of twenty-one residents) scored over 4 points on the General
      Health Questionnaire-12, indicating significant symptomatology (p < 0.01). The
      majority of subjects reported that a partner or spouse showed nondistressed
      levels of marital adjustment and satisfaction. All residents and nine of the
      twenty-five faculty members had mentors but judged the resource to be minimally
      beneficial. Resident burnout and psychiatric morbidity correlated with weekly
      work hours; conflict between the commitments of work and home life; discord with
      faculty, nursing staff, and senior residents; debt load; and work-related stress.
      Protective factors included being a parent, spending time with a spouse, having a
      physician father, and deriving satisfaction from discussing concerns with
      colleagues, friends, and family. CONCLUSIONS: In pursuit of our goal of
      determining the quality of life of orthopaedic residents and faculty, we
      identified a large disparity between the two groups. The resident group reported
      much greater levels of dysfunction particularly with regard to burnout and
      psychiatric morbidity. Furthermore, with regard to our second goal; our data
      revealed a number of risk factors for resident decompensation, most notably,
      increased workload, high debt levels, and discord with superiors. In addition,
      our research revealed that the current support interventions by the residency
      program, including mentoring and facilitation of spousal adjustment, are viewed
      as being of little help.

PMID- 15252112
TI  - What's new in spine surgery.

PMID- 15252113
TI  - Modulation of acto-myosin contractility in skeletal muscle myoblasts uncouples
      growth arrest from differentiation.
AB  - Cell-substratum interactions trigger key signaling pathways that modulate growth
      control and tissue-specific gene expression. We have previously shown that
      abolishing adhesive interactions by suspension culture results in G(0) arrest of
      myoblasts. We report that blocking intracellular transmission of adhesion
      dependent signals in adherent cells mimics the absence of adhesive contacts. We
      investigated the effects of pharmacological inhibitors of acto-myosin
      contractility on growth and differentiation of C2C12 myogenic cells. ML7 (5
      iodonaphthalene-1-sulfonyl homopiperazine) and BDM (2,3, butanedione monoxime)
      are specific inhibitors of myosin light chain kinase, and myosin heavy chain
      ATPase, respectively. ML7 and BDM affected cell shape by reducing focal adhesions
      and stress fibers. Both inhibitors rapidly blocked DNA synthesis in a dose
      dependent, reversible fashion. Furthermore, both ML7 and BDM suppressed
      expression of MyoD and myogenin, induced p27(kip1) but not p21(cip1), and
      inhibited differentiation. Thus, as with suspension-arrest, inhibition of acto
      myosin contractility in adherent cells led to arrest uncoupled from
      differentiation. Over-expression of inhibitors of the small GTPase RhoA (dominant
      negative RhoA and C3 transferase) mimicked the effects of myosin inhibitors. By
      contrast, wild-type RhoA induced arrest, maintained MyoD and activated myogenin
      and p21 expression. The Rho effector kinase ROCK did not appear to mediate Rho's
      effects on MyoD. Thus, ROCK and MLCK play different roles in the myogenic
      program. Signals regulated by MLCK are critical, since inhibition of MLCK
      suppressed MyoD expression but inhibition of ROCK did not. Inhibition of
      contractility suppressed MyoD but did not reduce actin polymer levels. However,
      actin depolymerization with latrunculin B inhibited MyoD expression. Taken
      together, our observations indicate that actin polymer status and contractility
      regulate MyoD expression. We suggest that in myoblasts, the Rho pathway and
      regulation of acto-myosin contractility may define a control point for
      conditional uncoupling of differentiation and the cell cycle.

PMID- 15252114
TI  - Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and
      motility of lymphoid cells and is PMA-sensitive.
AB  - Tyrosine phosphorylation of paxillin regulates actin cytoskeleton-dependent
      changes in cell morphology and motility in adherent cells. In this report we
      investigated the involvement of paxillin tyrosine phosphorylation in the
      regulation of actin cytoskeleton-dependent polarization and motility of a non
      adherent IL-3-dependent murine pre-B lymphocytic cell line Baf3. We also assessed
      the effect of phorbol myristate acetate (PMA), a phorbol ester analogous to those
      currently in clinical trials for the treatment of leukemia, on paxillin
      phosphorylation. Using tyrosine-to-phenylalanine phosphorylation mutants of
      paxillin and phosphospecific antibody we demonstrated that IL-3 stimulated
      phosphorylation of paxillin tyrosine residues 31 and 118, whereas the tyrosines
      40 and 181 were constitutively phosphorylated. Phosphorylation of paxillin
      residues 31 and 118 was required for cell polarization and motility. In the
      presence of IL-3, PMA dramatically reduced the phosphorylation of residues 31 and
      118, which was accompanied by inhibition of cell polarization and motility. This
      PMA effect was partially recapitulated by expression of exogenous tyrosine 31 and
      118 mutants of paxillin. We also demonstrated that PMA inhibited the IL-3-induced
      and activation-dependent tyrosine phosphorylation of focal adhesion kinase. Thus,
      our results indicate that phosphorylation of paxillin tyrosine residues 31 and
      118 regulates actin-dependent polarization and motility of pre-B Baf3 cells, both
      of which could be inhibited by PMA. They also suggest that inhibition of upstream
      signaling by PMA contributes to the decrease of paxillin phosphorylation and
      subsequent changes in cell morphology.

PMID- 15252115
TI  - Glycine, GABA and their transporters in pancreatic islets of Langerhans: evidence
      for a paracrine transmitter interplay.
AB  - To elucidate the possible roles of the CNS neurotransmitters glycine and GABA in
      neuroendocrine paracrine signalling, we investigated their localizations, and
      those of their transport proteins, by confocal immunofluorescence and
      quantitative post-embedding immuno-electron microscopy in the pancreatic islets
      of Langerhans. We show that A-cells contain glycine in synaptic-like
      microvesicles as well as in secretory granules. A-cells express the
      macromolecules necessary to: (1) concentrate glycine within both organelle types
      before release (the vesicular GABA/glycine transporter VGAT=VIAAT); and to (2)
      take up the transmitter from the extracellular space (the plasma membrane glycine
      transporter GLYT2). Also B-cells have glycine in their microvesicles and
      granules, but the microvesicle/cytosol ratio is lower than in A-cells, consistent
      with the presence of GABA (which competes with glycine for vesicular uptake) in
      the cytosol at a much higher concentration in B-cells than in A-cells. Both A-
      and B-cells contain GABA in their microvesicles and secretory granules, and the
      membranes of the two organelle types contain VGAT in both cell types. A-cells as
      well as B-cells express a plasma membrane transporter GAT3 that mediates uptake
      of GABA. The localization of VGAT in the cores of A-cell secretory granules, and
      in the secretory granule membranes in both cell types, indicates novel aspects of
      the mechanisms for release of glycine and GABA. The discovery that both A- and B
      cells possess the molecular machinery for the evoked release of both glycine and
      GABA from synaptic-like microvesicles suggests that both of the principal
      inhibitory transmitters in the brain participate in paracrine signalling in the
      pancreas.

PMID- 15252116
TI  - cAMP-induced degradation of cyclin D3 through association with GSK-3beta.
AB  - In this study we report a new mechanism whereby cyclic AMP (cAMP) regulates the
      cell-cycle machinery. We demonstrate that elevation of intracellular levels of
      cAMP promotes degradation of cyclin D3 in proteasomes, and that this occurs via
      glycogen synthase kinase-3beta (GSK-3beta)-mediated phosphorylation of cyclin D3
      at Thr-283. Elevation of cAMP did not change the subcellular distribution of
      either cyclin D3 or GSK-3beta. However, cAMP promoted the interaction between
      cyclin D3 and GSK-3beta both in vitro and in vivo, indicating that GSK-3beta
      mediated phosphorylation of cyclin D3 might require the association between the
      two proteins. These results demonstrate how cAMP enhances degradation of cyclin
      D3. Furthermore, we provide evidence for a novel mechanism by which GSK-3beta
      might phosphorylate unprimed substrates in vivo.

PMID- 15252117
TI  - Phospholipase C-gamma1 is a guanine nucleotide exchange factor for dynamin-1 and
      enhances dynamin-1-dependent epidermal growth factor receptor endocytosis.
AB  - Phospholipase C-gamma1 (PLC-gamma1), which interacts with a variety of signaling
      molecules through its two Src homology (SH) 2 domains and a single SH3 domain has
      been implicated in the regulation of many cellular functions. We demonstrate that
      PLC-gamma1 acts as a guanine nucleotide exchange factor (GEF) of dynamin-1, a 100
      kDa GTPase protein, which is involved in clathrin-mediated endocytosis of
      epidermal growth factor (EGF) receptor. Overexpression of PLC-gamma1 increases
      endocytosis of the EGF receptor by increasing guanine nucleotide exchange
      activity of dynamin-1. The GEF activity of PLC-gamma1 is mediated by the direct
      interaction of its SH3 domain with dynamin-1. EGF-dependent activation of ERK and
      serum response element (SRE) are both up-regulated in PC12 cells stably
      overexpressing PLC-gamma1, but knockdown of PLC-gamma1 by siRNA significantly
      reduces ERK activation. These results establish a new role for PLC-gamma1 in the
      regulation of endocytosis and suggest that endocytosis of activated EGF receptors
      may mediate PLC-gamma1-dependent proliferation.

PMID- 15252118
TI  - Visualization of unconstrained negative supercoils of DNA on polytene chromosomes
      of Drosophila.
AB  - Bulk DNA within the eukaryotic genome is torsionarily relaxed. However,
      unconstrained negative supercoils of DNA have been detected in few local domains
      of the genome through preferential binding of psoralen. To make a genome-wide
      survey for such domains, we introduced biotinylated psoralen into Drosophila
      salivary glands and visualized it on polytene chromosomes with fluorescent
      streptavidin. We observed bright psoralen signals on many transcriptionally
      active interbands and puffs. Upon heat shock, the signals appeared on heat-shock
      puffs. The signals were resistant to RNase treatment but disappeared or became
      faint by previous nicking of DNA or inhibition of transcription with alpha
      amanitin. These data show that transcription-coupled, unconstrained negative
      supercoils of DNA exist in approximately 150 loci within the interphase genome.

PMID- 15252119
TI  - Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent
      alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein
      ATRX.
AB  - Placing regulatory proteins into different multiprotein complexes should modify
      key cellular processes. Here, we show that the transcription repressor Daxx and
      the SWI/SNF protein ATRX are both associated with two intranuclear domains:
      ND10/PML bodies and heterochromatin. The accumulation of ATRX at nuclear domain
      10 (ND10) was mediated by its interaction with the N-terminus of Daxx. Binding of
      this complex to ND10 was facilitated by the interaction of the Daxx C-terminus
      with SUMOylated promyelocytic leukemia protein (PML). Although ATRX was present
      at heterochromatin during the entire cell cycle, Daxx was actively recruited to
      this domain at the end of S-phase. The FACT-complex member structure-specific
      recognition protein 1 (SSRP1) accumulated at heterochromatin simultaneously with
      Daxx and accumulation of both proteins depended on ATRX phosphorylation. Both
      Daxx and SSRP1 were released from heterochromatin early in G(2) phase and Daxx
      was recruited back to ND10, indicating that both proteins localize to
      heterochromatin during a very short temporal window of the cell cycle. ATRX seems
      to assemble a repression multiprotein complex including Daxx and SSRP1 at
      heterochromatin during a specific stage of the cell cycle, whereas Daxx functions
      as an adapter for ATRX accumulation at ND10. A potential functional consequence
      of Daxx accumulation at heterochromatin was found in the S- to G(2)-phase
      transition. In Daxx(-/-) cells, S-phase was accelerated and the propensity to
      form double nuclei was increased, functional changes that could be rescued by
      Daxx reconstitution and that might be the basis for the developmental problems
      observed in Daxx knockout animals.

PMID- 15252120
TI  - Genetic compensation for sarcoglycan loss by integrin alpha7beta1 in muscle.
AB  - Disruption of the sarcoglycan complex leads to muscle membrane instability and
      muscular dystrophy in humans and mice. Through the dystrophin glycoprotein
      complex, sarcoglycan participates in connecting the internal cytoskeleton to the
      membrane and the extracellular matrix. Integrin alpha7beta1 is also a
      transmembrane protein of skeletal and cardiac muscle that similarly links the
      cytoskeleton to the extracellular matrix. Mice lacking integrin alpha7 develop
      mild muscle degeneration, while sarcoglycan mutant mice display overt muscle
      degeneration and muscular dystrophy. In sarcoglycan-deficient muscle, integrin
      alpha7 protein was upregulated at the plasma membrane. To ascertain whether
      integrin alpha7 upregulation compensates for the loss of the transmembrane
      sarcoglycan linkage in sarcoglycan-deficient muscle, we generated mice lacking
      both integrin alpha7 and gamma-sarcoglycan (gxi). These double-mutant gxi mice
      exhibit profound, rapid muscle degeneration leading to death before one month of
      age consistent with a weakened cellular attachment to the extracellular matrix.
      The regenerative capacity of gxi muscle was intact with increased embryonic
      myosin heavy chain expression, myofiber central nucleation and normal in vivo
      myoblast differentiation. Therefore, upregulation of integrin alpha7beta1
      compensates as a transmembrane muscle cell attachment for sarcoglycan consistent
      with overlapping roles for sarcoglycan and integrins in mediating cytoskeletal
      membrane-extracellular matrix interaction.

PMID- 15252121
TI  - The Plasmodium falciparum Vps4 homolog mediates multivesicular body formation.
AB  - Members of the apicomplexan family of parasites contain morphologically unique
      secretory organelles termed rhoptries that are essential for host cell invasion.
      Rhoptries contain internal membranes, and thus resemble multivesicular bodies. To
      determine whether multivesicular body endosomal intermediates are formed in
      Apicomplexa, we used the Plasmodium falciparum homolog of the class E gene, Vps4,
      as a probe. Endogenous P. falciparum Vps4 (PfVps4) localized to the cytoplasm of
      P. falciparum trophozoites, and transgenic PfVps4 localized to the cytosol in P.
      falciparum, in the related parasite Toxoplasma gondii and in COS cells. When
      mutated to block ATP hydrolysis, transiently expressed PfVps4 localized instead
      to large vesicular structures in P. falciparum. The same construct, and another
      mutant blocked in ATP binding, generated large cholesterol-enriched
      multivesicular bodies in both COS cells and T. gondii. Mutant PfVps4 structures
      in T. gondii co-localized with markers for early endosomes. These results
      demonstrate a conservation of Vps4 function across wide phylogenetic boundaries,
      and indicate that endosomal multivesicular bodies form in both P. falciparum and
      T. gondii.

PMID- 15252123
TI  - The Rb network.

PMID- 15252124
TI  - Platelet adhesion signalling and the regulation of thrombus formation.
AB  - Platelets perform a central role in haemostasis and thrombosis. They adhere to
      subendothelial collagens exposed at sites of blood vessel injury via the
      glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin alpha(2)beta(1).
      These receptors perform distinct functions in the regulation of cell signalling
      involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk),
      adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3
      kinase. They are also coupled to an increase in cytosolic calcium levels and
      protein kinase C activation, leading to the secretion of paracrine/autocrine
      platelet factors and an increase in integrin receptor affinities. Through the
      binding of plasma fibrinogen and von Willebrand Factor to integrin
      alpha(IIb)beta(3), a platelet thrombus is formed. Although increasing evidence
      indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins
      alpha(2)beta(1) and alpha(IIb)beta(3) contribute to the signalling that regulates
      this process, the individual roles of each are only beginning to be dissected. By
      contrast, adhesion receptor signalling through platelet endothelial cell adhesion
      molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and
      thrombus formation in the healthy circulation. Recent studies indicate that
      understanding of platelet adhesion signalling mechanisms might enable the
      development of new strategies to treat and prevent thrombosis.

PMID- 15252125
TI  - Junctions and vesicular trafficking during Drosophila cellularization.
AB  - The cellularization that converts the syncytial Drosophila embryo into thousands
      of distinct cells is a hybrid form of cleavage. It derives from cytokinesis and
      has acquired specific features required for epithelial biogenesis.
      Cellularization generates an epithelial layer in which adjacent cells are
      connected by apical adherens junctions. If this process goes awry, subsequent
      development is dramatically affected, in particular tissue remodelling during
      gastrulation. Cellularization is associated with the invagination of the plasma
      membrane between adjacent nuclei at the cell cortex, the formation of a basal
      lateral surface and the assembly of apical adherens junctions. The regulated
      mobilization of intracellular pools of vesicles at defined sites of the plasma
      membrane underlies membrane growth and surface polarization. Genetic approaches
      have identified conserved core cellular pathways required for these processes,
      such as vesicular trafficking along the biosynthetic and endocytic routes, and
      vesicular insertion into the plasma membrane. The novel proteins Nullo and Slam,
      which are specifically induced during cellularization, represent developmental
      regulators of membrane growth during cellularization.

PMID- 15252126
TI  - Synergistic interaction between the Arp2/3 complex and cofilin drives stimulated
      lamellipod extension.
AB  - Both the Arp2/3 complex and cofilin are believed to be important for the
      generation of protrusive force at the leading edge; however, their relative
      contributions have not been explored in vivo. Our results with living cells show
      that cofilin enters the leading edge immediately before the start of lamellipod
      extension, slightly earlier than Arp2/3, which begins to be recruited slightly
      later as the lamellipod is extended. Blocking either the Arp2/3 complex or
      cofilin function in cells results in failure to extend broad lamellipods and
      inhibits free barbed ends, suggesting that neither factor on its own can support
      actin polymerization-mediated protrusion in response to growth factor
      stimulation. High-resolution analysis of the actin network at the leading edge
      supports the idea that both the severing activity of cofilin and the specific
      branching activity of the Arp2/3 complex are essential for lamellipod protrusion.
      These results are the first to document the relative contributions of cofilin and
      Arp2/3 complex in vivo and indicate that cofilin begins to initiate the
      generation of free barbed ends that act in synergy with the Arp2/3 complex to
      create a large burst in nucleation activity.

PMID- 15252127
TI  - CPD-photolyase adenovirus-mediated gene transfer in normal and DNA-repair
      deficient human cells.
AB  - Cyclobutane pyrimidine dimers (CPDs) are the most frequent and deleterious
      lesions generated in the mammalian genome after UV-C irradiation. The persistence
      of these lesions in DNA can be toxic and mutagenic, and also represents a
      specific signal to apoptosis. To investigate the CPDs repair in situ and
      consequent UV-induced apoptosis in human cells, we generated a recombinant
      adenovirus vector containing the gene encoding a CPD-photolyase-EGFP fusion
      protein (Adphr-EGFP). Adphr-EGFP-infected cells are proficient in photorepair,
      which prevents apoptotic cell death in comparison with samples kept in the dark,
      indicating that the fusion protein is functional in CPD recognition and removal.
      By using local UV irradiation, foci of the photolyase fusion protein were
      observed in UV-damaged areas of the nuclei in colocalization with NER enzymes.
      Phr-EGFP migration to CPD sites and redistribution after photorepair was
      followed, and shown to present similar kinetics in normal or DNA-repair-deficient
      cells. To our knowledge, this is the first report of an investigation of CPDs
      repair in situ employing a CPD-photolyase-EGFP enzyme. The Adphr-EGFP vector can
      be an informative tool to investigate the repair and cellular consequences of UV
      induced lesions in primary human cells.

PMID- 15252128
TI  - Inhibition of adipocyte differentiation by mechanical stretching through ERK
      mediated downregulation of PPARgamma2.
AB  - This study investigated the effects of cyclic stretching on adipocyte
      differentiation of mouse preadipocyte 3T3-L1 cells. Confluent 3T3-L1 cells were
      treated with dexamethasone, 3-isobutyl-1-methylxanthine and insulin for 45 hours
      (induction period), followed by incubation with insulin for 9 additional days
      (maturation period). A transient burst of CCAAT/enhancer-binding protein (C/EBP)
      beta and C/EBPdelta at an early stage (approximately 3 hours) and a delayed
      induction (approximately 45 hours) of C/EBPalpha and PPARgamma(2) were
      sequentially provoked during the induction period. Application of cyclic
      stretching during the entire induction period or only during the final 15 hours
      of the induction period significantly retarded the induction of glycerol-3
      phosphate dehydrogenase (GPDH) activity and the accumulation of intracellular
      triglycerides by the end of the maturation period. Cyclic stretching for the
      entire induction period, as well as that applied during the final 15 hours of the
      induction period, significantly reduced the expression of PPARgamma(2) mRNA,
      whereas reduction in the expression of C/EBPdelta mRNA was only observed in
      response to stretching that had been applied during the entire induction period.
      The expression of C/EBPalpha and C/EBPbeta mRNA did not change in response to
      stretching. Stretching induced the phosphorylation of extracellular-signal
      regulated protein kinases 1 and 2 (ERK1/2), which are members of the mitogen
      activated-protein kinase (MAPK) family, during the induction period. PD98,059, a
      MAPK/ERK kinase inhibitor, reversed the stretch-induced reduction of PPARgamma(2)
      at both mRNA and protein levels achieved during the induction period. PD98,059
      also restored GPDH activity and lipid droplet accumulation. Furthermore, the
      differentiation inhibited by the stretching was also restored by synthetic
      PPARgamma ligand. Collectively, these results suggest that the inhibition of
      adipocyte differentiation in response to stretching is mainly attributable to the
      reduced expression of PPARgamma(2), which is mediated by activation of the
      ERK/MAPK system.

PMID- 15252129
TI  - Cytosolic, nuclear and nucleolar localization signals determine subcellular
      distribution and activity of the NF-kappaB inducing kinase NIK.
AB  - It has been shown previously that the transcription factor NF-kappaB and its
      inhibitor IkappaBalpha shuttle constitutively between cytosol and nucleus.
      Moreover, we have recently demonstrated nucleocytoplasmic shuttling of the NF
      kappaB-inducing kinase NIK, a component of the NF-kappaB pathway, which is
      essential for lymph node development and B-cell function. Here we show that
      nuclear NIK also occurs in nucleoli and that this localization is mediated by a
      stretch of basic amino acids in the N-terminal part of the protein (R(143)-K-K-R
      K-K-K(149)). This motif is necessary and sufficient for nucleolar localization of
      NIK, as judged by nuclear localization of mutant versions of the full-length
      protein and the fact that coupling of these seven amino acids to GFP also leads
      to accumulation in nucleoli. Using fluorescence loss in photobleaching (FLIP) and
      fluorescence recovery after photobleaching (FRAP) approaches, we demonstrate a
      dynamic distribution between nucleoli and nucleoplasm and a high mobility of NIK
      in both compartments. Together with the nuclear export signal in the C-terminal
      portion of NIK that we have also characterized in detail, the nuclear/nucleolar
      targeting signals of NIK mediate dynamic circulation of the protein between the
      cytoplasmic, nucleoplasmic and nucleolar compartments. We demonstrate that
      nuclear NIK is capable of activating NF-kappaB and that this effect is diminished
      by nucleolar localization. Thus, subcellular distribution of NIK to different
      compartments might be a means of regulating the function of this kinase.

PMID- 15252130
TI  - Calcium binding protein 1 of the protozoan parasite Entamoeba histolytica
      interacts with actin and is involved in cytoskeleton dynamics.
AB  - Blocking expression of EhCaBP1, a calmodulin-like, four EF-hand protein from the
      protozoan parasite Entamoeba histolytica, resulted in inhibition of cellular
      proliferation. In this paper we report that EhCaBP1 is involved in dynamic
      changes of the actin cytoskeleton. Both endocytosis and phagocytosis were
      severely impaired in cells where EhCaBP1 expression was blocked by inducible
      expression of the antisense RNA. In wild-type cells both actin and EhCaBP1 were
      found to co-localize in phagocytic cups and in pseudopods. However, in antisense
      blocked cells the phagocytic cup formation is affected. Analysis of the staining
      patterns in the presence and absence of actin dynamics inhibitors, jasplakinolide
      and cytochalasin D suggested that EhCaBP1 and polymerized F-actin co-localize on
      membrane protrusions. Direct interaction between soluble EhCaBP1 and F-actin was
      further demonstrated by a co-sedimentation assay. A variant of EhCaBP1 did not
      bind F-actin showing the specificity of the interaction between EhCaBP1 and
      actin. There is no significant change in the kinetics of in vitro polymerization
      of actin in presence of EhCaBP1, indicating that EhCaBP1 does not affect filament
      treadmilling. In addition, using atomic force microscopy; it was found that
      filaments of F-actin, polymerized in presence of EhCaBP1, were thinner. These
      results indicate that EhCaBP1 may be involved in dynamic membrane restructuring
      at the time of cell pseudopod formation, phagocytosis and endocytosis in a
      process mediated by direct binding of EhCaBP1 to actin, affecting the bundling of
      actin filaments.

PMID- 15252131
TI  - Differential effects of a GTP-restricted mutant of Sar1p on segregation of cargo
      during export from the endoplasmic reticulum.
AB  - Export of cargo from the endoplasmic reticulum (ER) is the first membrane
      trafficking step in the secretory pathway. To date, all cargo proteins appear to
      use a common set of machinery for the initial stages of export, namely the COPII
      coat complex. Recent data from both yeast and mammalian systems have emerged
      suggesting that specific cargoes could be sorted from one another at the point of
      exit from the endoplasmic reticulum or immediately afterwards. Here, we have
      examined the mechanisms used for export of different types of cargo molecule from
      the endoplasmic reticulum. All cargoes examined utilise the COPII machinery, but
      specific differences are seen in the accumulation of cargo into ER-derived pre
      budding complexes following expression of a GTP-restricted mutant of the Sar1p
      GTPase. Glycosylphosphatidylinositol (GPI)-anchored GFP is seen to be restricted
      to the ER under these conditions whereas other cargoes, including ts045-G and
      lumFP accumulate in pre-budding complexes. Following exit, GPI-FP, lumFP and
      ts045-G-FP all travel to the Golgi in the same vesicular tubular clusters (VTCs).
      These data show a differential requirement for efficient GTP hydrolysis by the
      Sar1p GTPase in export of cargo from the ER.

PMID- 15252132
TI  - Tyrosine phosphorylation activates surface chaperones facilitating sperm-zona
      recognition.
AB  - Mammalian spermatozoa undergo a series of molecular and biochemical changes
      collectively termed capacitation prior to acquiring the ability to fertilise the
      oocyte. Although phosphorylation of sperm proteins on tyrosine residues has been
      recognised as an important component of this process, the precise relationship
      between the phosphorylation status of mammalian spermatozoa and their capacity
      for fertilisation has remained unclear. In this study we demonstrate a causal
      relationship between tyrosine phosphorylation in spermatozoa and sperm-zona
      interaction. The phosphotyrosine expression associated with sperm capacitation
      localised to internal flagellar structures in permeabilised cells but could also
      be detected on the exterior surface of the sperm head in live cells. Importantly,
      almost all spermatozoa bound to the zona pellucida demonstrated this pattern of
      phosphoprotein localisation, compared to fewer than 15% of the free-swimming
      population. These data suggest that tyrosine phosphorylation plays a significant
      role in remodelling the sperm surface, so that these cells are able to recognise
      the zona pellucida. Phosphoproteome analysis yielded the first evidence of
      molecular chaperones, endoplasmin (erp99) and heat shock protein 60 (hsp60), as
      targets for phosphorylation on the surface of mouse spermatozoa, whereas
      immunofluorescence localised these proteins to the precise region of the sperm
      head that participates in zona recognition. Based on these results, we propose a
      novel mechanism for mammalian gamete interaction whereby the activation of sperm
      surface chaperones by tyrosine phosphorylation during capacitation may trigger
      conformational changes facilitating the formation of a functional zona pellucida
      receptor complex on the surface of mammalian spermatozoa.

PMID- 15252133
TI  - The receptor for activated C-kinase-I (RACK-I) anchors activated PKC-beta on
      melanosomes.
AB  - Protein kinase C (PKC), a family of at least eleven isoforms, mediates numerous
      cell functions. In human melanocytes, alpha, beta, delta, epsilon and zeta
      isoforms of PKC are expressed, but uniquely PKC-beta activates tyrosinase, the
      key and the rate-limiting enzyme in melanogenesis, by phosphorylating specific
      serine residues on its cytoplasmic domain. To investigate the mechanism by which
      only PKC-beta phosphorylates tyrosinase, we examined the expression of receptor
      for activated C-kinase-I (RACK-I), a receptor specific for activated PKC-beta, on
      the surface of melanosomes, the specialized organelle in which melanogenesis
      occurs. Immunoblot analysis of purified melanosomes revealed that RACK-I is
      readily detectable. Immunoprecipitation of RACK-I from purified melanosomes,
      followed by immunoblot analysis using antibody against PKC-beta, revealed
      abundant PKC-beta, whereas PKC-alpha was not detected when immunoblot analysis
      was performed using antibody against PKC-alpha. Activation of PKC in melanocytes
      increased the level of PKC-beta co-immunoprecipitated with RACK-I, while the
      level of melanosome-associated RACK-I decreased when melanocytes were treated
      chronically with the 12-0-tetradecanoyl-phorbol 13-Acetate (TPA), a condition
      known to deplete PKC and reduce tyrosinase activity. Immunoprecipitation with
      RACK-I antibody co-precipitated fewer PKC-beta in the presence of UV-activated 1,
      1'-decamethylenebis-4-aminoquinaldinium di-iodide (DECA), known to disrupt the
      interaction between activated PKC-beta and RACK-I. Treatment of intact
      melanocytes with DECA also decreased tyrosinase activity. Moreover, suppression
      of RACK-I expression by transfecting melanocytes with siRNA against RACK-I
      reduced the basal tyrosinase activity and blocked TPA-induced increases in
      tyrosinase activity. Taken together, these results demonstrate that RACK-I
      anchors activated PKC-beta on the melanosome membrane, allowing PKC-beta to
      phosphorylate tyrosinase.

PMID- 15252134
TI  - Drosophila Klp67A is required for proper chromosome congression and segregation
      during meiosis I.
AB  - Drosophila Klp67A belongs to the Kip3 subfamily of Kinesin-type microtubule
      catastrophe factors. In primary spermatocytes, loss of klp67A leads to defects in
      karyokinesis and cytokinesis. We show that these cells formed disorganised,
      bipolar spindles that contained increased numbers of microtubules. The
      kinetochore fibres were wavy and bent, whereas astral microtubules appeared
      abnormally robust and formed cortical bundles. Time-lapse studies revealed that
      during biorientation, the chromosomes in klp67A mutant cells continued to
      reorient for about twice as long as those in control cells. Metaphase plates were
      poorly defined in the mutants and often formed at non-equatorial positions.
      Consistent with the above abnormalities in chromosome congression, we found that
      in wild-type cells Klp67A associated with prometaphase/metaphase kinetochores
      before redistributing to the central spindle at anaphase onset. Although the
      timing of this redistribution of kinetochores argues against a role in anaphase
      chromosome segregation, dyads in the mutants disjoined but exhibited greatly
      diminished poleward velocities. They travelled on average at approximately 34% of
      the velocity of their wild-type counterparts and often decondensed at non-polar
      locations. Hypomorphic mutations of klp67A may lead to segregation defects.

PMID- 15252135
TI  - N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies
      and the Golgi, and has a potential role in protein trafficking.
AB  - N4WBP5A (Ndfip2) belongs to an evolutionarily conserved group of Nedd4
      interacting proteins with two homologues in mammalian species. We have previously
      shown that N4WBP5A expression in Xenopus oocytes results in increased cell
      surface expression of the epithelial sodium channel. N4WBPs are characterized by
      one or two amino terminal PPxY motifs and three transmembrane domains. Here we
      show that both PPxY motifs of N4WBP5A mediate interaction with WW domains of
      Nedd4 and that N4WBP5A can physically interact with the WW domains of several
      Nedd4-family proteins. N4WBP5A is ubiquitinated and ubiquitination does not
      significantly affect the turnover of N4WBP5A protein. Ubiquitination of N4WBP5A
      is enhanced by Nedd4 and Nedd4-2 expression. N4WBP5A localizes to the Golgi,
      vesicles associated with the Golgi complex and to multivesicular bodies. We show
      that the ectopic expression of N4WBP5A inhibits receptor-mediated endocytosis of
      labelled epidermal growth factor. N4WBP5A overexpression inhibits accumulation of
      EGF in large endocytic/lysosomal vesicles suggestive of a role for N4WBP5A in
      protein trafficking. We propose that N4WBP5A acts as an adaptor to recruit Nedd4
      family ubiquitin-protein ligases to the protein trafficking machinery.

PMID- 15252136
TI  - KIN17 encodes an RNA-binding protein and is expressed during mouse
      spermatogenesis.
AB  - Genotoxic agents deform DNA structure thus eliciting a complex genetic response
      allowing recovery and cell survival. The Kin17 gene is up-regulated during this
      response. This gene encodes a conserved nuclear protein that shares a DNA-binding
      domain with the bacterial RecA protein. The KIN17 protein binds DNA and displays
      enhanced expression levels in proliferating cultured cells, suggesting a role in
      nuclear metabolism. We investigated this by studying the expression profile of
      KIN17 protein during mouse spermatogenesis. As expected, the expression level of
      Kin17 is higher in proliferating than in differentiated cells. KIN17 is
      selectively extracted from this tissue by detergents and a fraction was tightly
      associated with the nuclear matrix. Germinal cells ubiquitously express Kin17 and
      the protein is located mainly in the nucleus except in elongated spermatids where
      cytoplasmic staining is also observed. Sertoli and germ cells that are no longer
      mitotically active express KIN17, suggesting a general role in all testicular
      cell types. In adult testis a significant proportion of KIN17 co-purifies with
      polyadenylated RNA. KIN17 directly binds RNA, preferentially poly(G) and poly(U)
      homopolymers. These results together with the identification of KIN17 as a
      component of the human spliceosome indicate that this protein may participate in
      RNA processing.

PMID- 15252137
TI  - Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of
      phosphoinositide-3-kinase signaling.
AB  - We have developed biologically stable semisynthetic viridins as inhibitors of
      phosphoinositide (PtdIns)-3-kinases. The most active compound was PX-866 (acetic
      acid (1S,4E,10R,11R,13S,14R)-[4-diallylaminomethylene-6-hydroxy-1-methoxymethyl
      10,13-dimethyl-3,7,17-trioxo-1,3,4,7,10,11,12,13,14,15,16,17-dodecahydro-2-oxa
      cyclopenta[a]phenanthren-11-yl ester), which inhibited purified PtdIns-3-kinase
      with an IC50 of 0.1 nmol/L and PtdIns-3-kinase signaling measured by phospho
      Ser473-Akt levels in HT-29 colon cancer cells with an IC50 of 20 nmol/L. PX-866
      administered to mice at 10 mg/kg inhibited phospho-Ser473-Akt in HT-29 colon
      tumor xenografts up to 80% with recovery taking >48 hours after p.o.
      administration but more rapidly after i.v. or i.p. administration. PX-866 was
      eliminated from mouse plasma with a half-life of 18 minutes and a clearance of
      360 mL/min/kg following i.v. administration and, when administered i.p. or p.o.,
      showed first-pass metabolism with sequential N-deallylation. Synthetic standards
      of the N-deallylated metabolites of PX-866 inhibited PtdIns-3-kinase at low
      nanomolar per liter concentrations. PX-866 exhibited in vivo antitumor activity
      against s.c. OvCar-3 human ovarian cancer and A-549 human lung cancer xenografts
      in immunodeficient mice with log cell kills up to 1.2. PX-866 also increased the
      antitumor activity of cisplatin against A-549 xenografts and radiation treatment
      against OvCar-3 xenografts. The results show that PX-866 is a biologically stable
      broad-spectrum PtdIns-3-kinase inhibitor with good pharmacokinetics that causes
      prolonged inhibition of PtdIns-3-kinase signaling in human tumor xenografts. PX
      866 exhibits single agent in vivo antitumor activity and increases the antitumor
      effects of cisplatin and radiation treatment.

PMID- 15252138
TI  - Down-regulation of protein kinase Ceta potentiates the cytotoxic effects of
      exogenous tumor necrosis factor-related apoptosis-inducing ligand in PC-3
      prostate cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a highly
      promising candidate for the treatment of cancer because it elicits cell death in
      the majority of tumor cells while sparing most normal cells. Some cancers,
      however, display resistance to TRAIL, suggesting that treatment with TRAIL alone
      may be insufficient for cancer therapy. In the present study, we explored whether
      the apoptotic responsiveness of PC-3 prostate cancer cells to TRAIL could be
      enhanced by targeting the novel protein kinase C (PKC) isoform eta. Transfection
      of PC-3 cells with second-generation chimeric antisense oligonucleotides against
      PKCeta caused a time- and dose-dependent knockdown of PKCeta, as revealed by real
      time RT-PCR and Western blot analyses. Knockdown of PKCeta resulted in a marked
      amplification of TRAIL's cytotoxic activity. Cell killing could be substantially
      prevented by the pan-caspase inhibitor z-VAD-fmk. In addition, PKCeta knockdown
      and administration of TRAIL significantly synergized in activation of caspase-3
      and internucleosomal DNA fragmentation. Knockdown of PKCeta augmented TRAIL
      induced dissipation of the mitochondrial transmembrane potential and release of
      cytochrome c from mitochondria into the cytosol, indicating that PKCeta acts
      upstream of mitochondria. We conclude that PKCeta represents a considerable
      resistance factor with respect to TRAIL and a promising target to exploit the
      therapeutic potential of TRAIL.

PMID- 15252139
TI  - Lack of neurotoxicity of the vascular targeting agent ZD6126 following repeated
      i.v. dosing in the rat.
AB  - The vascular targeting agent ZD6126 is a water-soluble prodrug of N
      acetylcolchinol that acts by disrupting the cytoskeleton of tumor endothelial
      cells. It is currently undergoing clinical evaluation in man. As peripheral
      neuropathy is a major dose-limiting toxicity associated with tubulin binding
      agents, the neurotoxic potential of ZD6126 was investigated in male and female
      Wistar rats. ZD6126 was administered i.v. at up to maximum tolerated doses using
      subacute (0 to 20 mg/kg/d for 5 days) and chronic (0 to 10 mg/kg/d for 5 days,
      repeated monthly for 6 months) dosing regimens. A separate study examined a
      combination of ZD6126 (three cycles of ZD6126 given as in the chronic dosing
      regimen) and paclitaxel (12 mg/kg/wk for 9 weeks) to assess whether
      coadministration of ZD6126 altered the time course or magnitude of a paclitaxel
      induced neuropathy. Neurotoxic potential was examined using a comprehensive
      series of tests including a functional observation battery, measurements of
      muscle strength (forelimb and hind limb grip strength), nociception (tail flick
      test), locomotor activity, neuropathology, and whole nerve electrophysiology.
      There was no evidence that ZD6126 induced neurotoxicity in the rat following
      either subacute or chronic i.v. dosing. In a chronic electrophysiology study,
      ZD6126 produced a slight slowing of the maturational increase of caudal nerve
      amplitude, with some evidence of reversibility. However, this was not associated
      with any changes in caudal nerve conduction velocity, motor nerve conduction
      velocity or amplitude, functional observation battery behavioral and function
      parameters (including no effects on tail flick latency), and neuropathology. As
      expected, paclitaxel administration was associated with a significant decrease in
      caudal nerve conduction velocity (P = 0.0001). Coadministration of ZD6126 did not
      increase the neurotoxicity of paclitaxel. These studies suggest that ZD6126
      should not induce the peripheral neuropathy associated with other antitubulin
      chemotherapeutic agents and that ZD6126 may not exacerbate the neurotoxicity of
      other agents with dose-limiting neuropathies.

PMID- 15252140
TI  - A hybrid fibronectin motif protein as an integrin targeting selective tumor
      vascular thrombogen.
AB  - Targeted thrombotic eradication of solid tumors is a novel therapeutic strategy.
      The feasibility, efficacy, selectivity, and safety are dependent on multiple
      variables of protein design, molecular assembly, vascular target, and exclusive
      restriction of function to the tumor vasculature. To advance this strategy, we
      describe a design of an integrin targeting selective tumor vascular thrombogen.
      We adopted the fibronectin structural motif of tandem repeating modules with four
      type III repeat modules of fibronectin followed by two structurally homologous
      modules of the extracellular domain of tissue factor. This hybrid protein of six
      tandem modules recognizes integrins and selectively docks and initiates the
      thrombogenic protease cascade locally on the target cell surfaces. The protein is
      inactive in blood but is functionally active once assembled on integrin-positive
      cells. When administered i.v. to tumor-bearing mice, it selectively induces
      extensive local microthrombosis of the tumor microvasculature. The principles are
      addressed from the perspective of protein structural design for a class of
      selective tumor vascular thrombogen proteins that, through interaction with tumor
      angiogenic endothelium, elicit thrombotic occlusion rather than apoptosis or
      arrest of angiogenesis. This response can produce local tumor infarction followed
      by intratumoral ischemia-reperfusion injury, inflammation, and a local host tumor
      eradicative response.

PMID- 15252141
TI  - Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related
      apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through
      suppression of IkappaBalpha phosphorylation.
AB  - Epidemiologic studies suggest that diet rich in plant-derived foods plays an
      important role in the prevention of prostate cancer. Curcumin, the yellow pigment
      in the spice turmeric, has been shown to exhibit chemopreventive and growth
      inhibitory activities against multiple tumor cell lines. We have shown previously
      that curcumin and tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)/Apo2L interact to induce cytotoxicity in the LNCaP prostate cancer cell
      line. In this study, we investigated the mechanism by which curcumin augments
      TRAIL-induced cytotoxicity in LNCaP cells. Subtoxic concentrations of the
      curcumin-TRAIL combination induced strong apoptotic response in LNCaP cells as
      demonstrated by the binding of Annexin V-FITC and cleavage of procaspase-3.
      Furthermore, LNCaP cells express constitutively active nuclear factor-kappaB (NF
      kappaB), which is inhibited by curcumin. Because NF-kappaB has been shown to
      mediate resistance to TRAIL-induced apoptosis in tumor cells, we investigated
      whether there is a relationship between NF-kappaB activation and resistance to
      TRAIL in LNCaP prostate cancer cells. Pretreatment with curcumin inhibited the
      activation of NF-kappaB and sensitized LNCaP cells to TRAIL. A similar increase
      in the sensitivity of LNCaP cells to TRAIL-induced apoptosis was observed
      following inhibition of NF-kappaB by dominant negative mutant IkappaBalpha, an
      inhibitor of NF-kappaB. Finally, curcumin was found to inhibit NF-kappaB by
      blocking phosphorylation of IkappaBalpha. We conclude that NF-kappaB mediates
      resistance of LNCaP cells to TRAIL and that curcumin enhances the sensitivity of
      these tumor cells to TRAIL by inhibiting NF-kappaB activation by blocking
      phosphorylation of IkappaBalpha and its degradation.

PMID- 15252142
TI  - Polyamine catabolism in platinum drug action: Interactions between oxaliplatin
      and the polyamine analogue N1,N11-diethylnorspermine at the level of
      spermidine/spermine N1-acetyltransferase.
AB  - A great deal of experimental evidence connects induction of polyamine catabolism
      via spermidine/spermine N1-acetyltransferase (SSAT) to antiproliferative activity
      and apoptosis. Following our initial observation from gene expression profiling
      that platinum drugs induce SSAT, we undertook this present study to characterize
      platinum drug induction of SSAT and other polyamine catabolic enzymes and to
      examine how these responses might be enhanced with the well-known inducer of SSAT
      and clinically relevant polyamine analogue, N1,N11-diethylnorspermine (DENSPM).
      The results obtained in A2780 ovarian cancer cells by real-time quantitative RT
      PCR and Northern blot analysis show that a 2-hour exposure of A2780 cells to
      platinum drugs induces expression of SSAT, a second SSAT (SSAT-2), spermine
      oxidase, and polyamine oxidase in a dose-dependent manner. At equitoxic doses,
      oxaliplatin is more effective than cisplatin in SSAT induction. The most affected
      enzyme, SSAT, increased 15-fold in mRNA expression and 2-fold in enzyme activity.
      When combined with DENSPM to further induce SSAT and to enhance conversion of
      mRNA to activity, oxaliplatin increased SSAT mRNA 50-fold and activity, 210-fold.
      Polyamine pools declined in rough proportion to levels of SSAT induction. At
      pharmacologically relevant oxaliplatin exposure times (20 hours) and drug
      concentrations (5 to 15 micromol/L), these responses were increased even further.
      Combining low-dose DENSPM with oxaliplatin produced a greater than additive
      inhibition of cell growth based on the sulforhodamine-B assay. Taken together,
      the findings confirm potent induction of polyamine catabolic enzymes, such as
      SSAT by platinum drugs, and demonstrate that these biochemical responses as well
      as growth inhibition can be potentiated by co-treatment with the polyamine
      analogue DENSPM. With appropriate in vitro and in vivo optimization, these
      findings could lead to clinically relevant therapeutic strategies.

PMID- 15252143
TI  - Role of the transcription factor Ets-1 in cisplatin resistance.
AB  - Cisplatin is a DNA damaging agent widely used as a chemotherapeutic agent. A
      major limitation of the use of this agent is the development of drug resistance
      within tumors. Several in vitro models exist which enable the investigation of
      resistance mechanisms, including 2008/C13* ovarian carcinoma cells. C13* cells
      are variants of 2008 cells, displaying cisplatin resistance following 13
      consecutive cisplatin treatments. This model system has led to the identification
      of several mechanisms that play parts in the multifactorial nature of cisplatin
      resistance. In this study, we have examined the contribution of a transcription
      factor, Ets-1, to the cisplatin resistance of C13* cells. Ets-1 is up-regulated
      in C13* cells as compared with the cisplatin-sensitive 2008 cells and
      overexpression of this protein in 2008 cells led to a 7-fold increase in
      resistance. Further studies on a colorectal carcinoma cell line overexpressing
      Ets-1 indicated that this phenomenon is not cell specific-increased cisplatin
      resistance correlated to Ets-1 expression. The mechanism of cisplatin resistance
      elicited by Ets-1 is potentially via transcriptional activation of genes whose
      products have well-described functions in reducing cisplatin toxicity. Examples,
      identified via microarray analysis, include metallothioneins and DNA repair
      enzymes. This is the first report to our knowledge associating expression of Ets
      1, a transcription factor whose expression often signals poor prognosis in
      various cancer types, to cisplatin resistance.

PMID- 15252144
TI  - Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA
      and reversal of paclitaxel resistance in human ovarian cancer cells.
AB  - Ovarian cancer is currently the most lethal gynecologic malignancy in developed
      countries, and paclitaxel is a cornerstone in the treatment of this malignancy.
      Unfortunately, the efficacy of paclitaxel is limited by the development of drug
      resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1)
      overexpression, and in vitro paclitaxel resistance typically demonstrates
      overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel
      resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the
      role of these transporters in paclitaxel-resistant ovarian cancer cells, small
      interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the
      paclitaxel-resistant SKOV-3TR and OVCAR8TR ovarian cancer cell lines. Treatment
      of these lines with either chemically synthesized siRNAs or transfection with
      specific vectors that express targeted siRNAs demonstrated decreased mRNA and
      protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4
      fold reduction of paclitaxel resistance in the lines treated with the synthesized
      siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the
      cell lines transfected with siRNA of ABCB1 expressing vectors. ABCB4 siRNA
      treated cell lines showed minor reduction in paclitaxel resistance. These results
      indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian
      cancer cells in vitro and suggest that siRNA treatment may represent a new
      approach for the treatment of ABCB1-mediated drug resistance.

PMID- 15252145
TI  - Activation of protein kinase C betaII/epsilon-c-Jun NH2-terminal kinase pathway
      and inhibition of mitogen-activated protein/extracellular signal-regulated kinase
      1/2 phosphorylation in antitumor invasive activity induced by the polymethoxy
      flavonoid, nobiletin.
AB  - Flavonoids from medicinal plants have been therapeutically administered for
      cancer therapy. We recently reported that nobiletin (5,6,7,8,3',4'-hexamethoxy
      flavone) exhibits novel antitumor invasive activities by suppressing the
      production of pro-matrix metalloproteinases (proMMPs) and augmenting the
      expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in
      vitro. In the present study, intracellular target molecules associated with the
      actions of nobiletin against tumor invasion were identified. Nobiletin inhibited
      the phosphorylation of mitogen-activated protein/extracellular signal-regulated
      kinase (MEK) 1/2, but not the activity of Ras or the phosphorylation of Raf.
      Moreover, a MEK1/2 inhibitor, U0126, mimicked nobiletin's ability to decrease the
      production of proMMPs-1 and 9 in human fibrosarcoma HT-1080 cells stimulated by
      12-O-tetradecanoyl phorbol-13-acetate (TPA). In addition, neither the activity of
      phosphatidylinositol 3-kinase (PI3K) nor the phosphorylation of Akt was
      influenced by nobiletin. However, nobiletin was found to augment the
      phosphorylation of c-Jun NH2-terminal kinase (JNK), a downstream signal factor of
      the PI3K-Akt pathway, in TPA-treated HT-1080 cells. A similar augmentation of JNK
      phosphorylation was observed on treatment with a PI3K inhibitor, LY-294002.
      Furthermore, nobiletin enhancement of TIMP-1 production in TPA-stimulated HT-1080
      cells was found to be diminished by adding a JNK inhibitor, SP600125. Moreover,
      protein kinase C (PKC) inhibitor experiments showed that PKCbetaII/epsilon were
      associated with the nobiletin-mediated augmentation of JNK phosphorylation.
      Therefore, these results introduce novel evidence that the antitumor effects of
      nobiletin are finely regulated by the following intracellular mechanisms: (1) the
      inhibition of MEK1/2 activity is involved in the suppression of MMP expression
      and (2) the activation of the novel PKCbetaII/epsilon-JNK pathway is associated
      with the augmentation of TIMP-1 expression.

PMID- 15252146
TI  - In vitro evaluation of dimethane sulfonate analogues with potential alkylating
      activity and selective renal cell carcinoma cytotoxicity.
AB  - We identified five structurally related dimethane sulfonates with putative
      selective cytotoxicity in renal cancer cell lines. These compounds have a
      hydrophobic moiety linked to a predicted alkylating group. A COMPARE analysis
      with the National Cancer Institute Anticancer Drug Screen standard agent database
      found significant correlations between the IC50 of the test compounds and the
      IC50 of alkylating agents (e.g., r = 0.68, P < 0.00001 for chlorambucil). In this
      report, we examined whether these compounds had activities similar to those of
      conventional alkylating agents. In cytotoxicity studies, chlorambucil-resistant
      Walker rat carcinoma cells were 4- to 11-fold cross-resistant to the test
      compounds compared with 14-fold resistant to chlorambucil. To determine effects
      on cell cycle progression, renal cell carcinoma (RCC) line 109 was labeled with
      bromodeoxyuridine prior to drug treatment. Complete cell cycle arrest occurred in
      cells treated with an IC90 dose of NSC 268965. p53 protein levels increased as
      much as 5.7-fold in RCC line 109 and as much as 20.4-fold in breast cancer line
      MCF-7 following an 18-hour drug exposure. Finally, DNA-protein cross-links were
      found following a 6-hour pretreatment with all compounds. Thus, the dimethane
      sulfonate analogues have properties expected of some alkylating agents but,
      unlike conventional alkylating agents, appear to possess activity against RCC.

PMID- 15252147
TI  - Transcriptional signature of flavopiridol-induced tumor cell death.
AB  - Flavopiridol has been shown to inhibit the proliferation of a variety of human
      tumor cells and is currently undergoing clinical evaluation in cancer treatment.
      Although the antiproliferative effect of flavopiridol has been attributed to the
      inhibition of cyclin-dependent kinases 2 and 4, recent reports indicate that the
      mechanism responsible for the cell death induced by this agent is more complex.
      To provide insight into the molecular processes mediating flavopiridol-induced
      cytotoxicity and to investigate the availability of markers indicative of its
      activity, we have applied cDNA microarray technology. Gene expression profiles
      were determined for four human tumor cell lines (prostate carcinomas PC3 and
      DU145 and gliomas SF359 and U251) following exposure to selected concentrations
      of flavopiridol. Treatment of these cell lines with a concentration of
      flavopiridol sufficient to reduce survival to 10% resulted in the identification
      of a set of 209 genes, the expression of which were altered in each of the cell
      lines. This common set of 209 gene expression changes suggested that flavopiridol
      induced cell death can be defined in terms of a specific transcriptome. The
      flavopiridol death transcriptome consisted primarily of down-regulated genes;
      however, there were also a significant number of genes with increased expression.
      Whereas causal relationships were not established, these data suggest molecular
      events/processes that may be associated with flavopiridol-induced tumor cell
      death. Moreover, the identification of a set of gene expression changes in four
      human tumor cell lines suggests that such a transcriptome may be applicable to
      investigations of flavopiridol pharmacodynamics.

PMID- 15252148
TI  - Gene profiling and the cyclin-dependent kinase inhibitor flavopiridol: what's in
      a name?

PMID- 15252149
TI  - Selenite-induced p53 Ser-15 phosphorylation and caspase-mediated apoptosis in
      LNCaP human prostate cancer cells.
AB  - The issue of p53 requirement for the caspase-mediated apoptosis induced by
      selenium in a cancer chemoprevention or chemotherapy context has not been
      critically addressed. We and others have shown that selenite induces apoptotic
      DNA laddering in the p53-mutant DU145 prostate cancer cells and the p53-null HL60
      leukemia cells without the cleavage of poly(ADP-ribose) polymerase (PARP; i.e.,
      caspase-independent apoptosis), whereas selenium compounds leading to the
      formation of methylselenol induce caspase-mediated apoptosis in these cells.
      Because selenite induces DNA single strand breaks, and because certain types of
      DNA damage activate p53, we investigated whether the human LNCaP prostate cancer
      cells, which contain a wild-type p53, execute selenite-induced apoptosis through
      caspase pathways. The results showed that exposure of LNCaP cells for 24 hours to
      lower micromolar concentrations of selenite led to DNA laddering, and to the
      cleavage of PARP and several pro-caspases. In contrast to this apoptosis
      sensitivity, LNCaP cells were rather resistant to similar concentrations of the
      methylselenol precursor methylseleninic acid. Selenite treatment led to a
      significant increase in p53 phosphorylation on Ser-15 (Ser15P). Time course
      experiments showed that p53 Ser15P occurred several hours before caspase
      activation and PARP cleavage. The general caspase inhibitor zVADfmk completely
      blocked PARP cleavage, and significantly decreased DNA laddering, but did not
      affect p53 Ser15P. An inhibitor for caspase-8 was equally as protective as that
      for caspase-9 against the selenite-induced apoptosis. Attenuating p53 by a
      chemical inhibitor pifithrin-alpha decreased the selenite-induced p53 Ser15P and
      led to concordant reductions of PARP cleavage and apoptosis. In summary, selenite
      induced p53 Ser15P appeared to be important for activating the caspase-mediated
      apoptosis involving both the caspase-8 and the caspase-9 pathways in the LNCaP
      cells.

PMID- 15252150
TI  - A strategy for cancer prevention: stimulation of the Nrf2-ARE signaling pathway.
AB  - Many genes, with products involved in the protection of cells against
      carcinogens, oxidants, and other toxic chemicals, are under the transcriptional
      control of a simple DNA regulatory element [i.e., the antioxidant response
      element (ARE)]. One or more functional AREs have been confirmed or are believed
      to exist in the upstream region of many anticarcinogenic/antioxidant genes and
      have been shown to mediate the coordinate transcriptional up-regulation of these
      genes by many chemical agents [i.e., the ARE-mediated inducers]. There is strong
      evidence that increased expression of ARE-regulated genes inhibits cancer
      development. The signaling system leading to ARE activation has been partly
      elucidated, and nuclear factor erythroid 2-related factor 2 (Nrf2) has been
      identified as the key transcriptional factor that serves to transmit the inducer
      signal to ARE. It is now known that nuclear factor erythroid 2-related factor 2,
      which is normally sequestered in the cytoplasm by Kelch-like ECH-associated
      protein 1, dissociates from Kelch-like ECH-associated protein 1 on exposure to
      ARE-mediated inducers, translocates to the nucleus, complexes with other nuclear
      factors, and binds to ARE. Rapid and simple assays have been devised to identify
      chemical agents that can stimulate this signaling pathway. Moreover, many ARE
      mediated inducers have been identified, and several of them have shown promising
      cancer preventive activity.

PMID- 15252151
TI  - ChIP Display: novel method for identification of genomic targets of transcription
      factors.
AB  - Novel protein-DNA interactions in mammalian cells are traditionally discovered in
      the course of promoter studies. The genomic era presents opportunities for the
      reverse; namely, the discovery of novel target genes for transcription factors of
      interest. Chromatin immunoprecipitation (ChIP) is typically used to test whether
      a protein binds to a candidate promoter in living cells. We developed a new
      method, ChIP Display (CD), which allows genome-wide unbiased identification of
      target genes occupied by transcription factors of interest. Initial CD
      experiments pursuing target genes for RUNX2, an osteoblast master transcription
      factor, have already resulted in the identification of four genes that had never
      been reported as targets of RUNX2. One of them, Osbpl8, was subjected to mRNA and
      promoter-reporter analyses, which provided functional proof for its regulation by
      RUNX2. CD will help to assemble the puzzle of interactions between transcription
      factors and the genome.

PMID- 15252152
TI  - Conservative homologous recombination preferentially repairs DNA double-strand
      breaks in the S phase of the cell cycle in human cells.
AB  - DNA double-strand breaks (DSBs) are repaired by either homologous recombination
      (HR) or non-homologous end joining (NHEJ) in mammalian cells. Repair with NHEJ or
      HR using single-strand annealing (SSA) often results in deletions and is
      generally referred to as non-conservative recombination. Error-free, conservative
      HR involves strand invasion and requires a homologous DNA template, and therefore
      it is generally believed that this type of repair occurs preferentially in the
      late S, G2 and M phases of the cell cycle, when the sister chromatid is
      available. There are several observations supporting this hypothesis, although it
      has not been tested directly. Here, we synchronize human SW480SN.3 cells in the
      G1/G0 (with serum starvation), S (with thymidine block) and M (with nocodazole)
      phases of the cell cycle and investigate the efficiency of conservative HR repair
      of an I-SceI-induced DSB. The frequency of HR repair of DSBs was 39 times higher
      in S-phase cells than in M-phase cells and 24-fold higher than in G1/G0 cells.
      This low level of conservative HR occurs even though a homologous template is
      present within the recombination substrate. We propose that this can be explained
      by an absence of recombination proteins outside the S phase or alternatively that
      there maybe factors that suppress HR in G1/G0 and M. Furthermore, we found that
      HR repair of DSBs involves short tract gene conversion in all the phases of the
      cell cycle. This indicates that the same pathway for conservative HR is employed
      in the repair of DSBs regardless of phase of the cell cycle and that only the
      frequency is affected.

PMID- 15252153
TI  - Genome-wide operon prediction in Staphylococcus aureus.
AB  - Identification of operon structure is critical to understanding gene regulation
      and function, and pathogenesis, and for identifying targets towards the
      development of new antibiotics in bacteria. Recently, the complete genome
      sequences of a large number of important human bacterial pathogens have become
      available for computational analysis, including the major human Gram-positive
      pathogen Staphylococcus aureus. By annotating the predicted operon structure of
      the S.aureus genome, we hope to facilitate the exploration of the unique biology
      of this organism as well as the comparative genomics across a broad range of
      bacteria. We have integrated several operon prediction methods and developed a
      consensus approach to score the likelihood of each adjacent gene pair to be co
      transcribed. Gene pairs were separated into distinct operons when scores were
      equal to or below an empirical threshold. Using this approach, we have generated
      a S.aureus genome map with scores annotated at the intersections of every
      adjacent gene pair. This approach predicted about 864 monocistronic transcripts
      and 533 polycistronic operons from the protein-encoding genes in the S.aureus
      strain Mu50 genome. When compared with a set of experimentally determined
      S.aureus operons from literature sources, this method successfully predicted at
      least 91% of gene pairs. At the transcription unit level, this approach correctly
      identified at least 92% of complete operons in this dataset. This consensus
      approach has enabled us to predict operons with high accuracy from a genome where
      limited experimental evidence for operon structure is available.

PMID- 15252154
TI  - Patient referral is influenced by dialysis centre structure in the Diamant Alpin
      Dialysis cohort study.
AB  - BACKGROUND: Late referral (LR) to the nephrologist of patients with progressing
      chronic kidney disease (CKD) has numerous deleterious effects and is observed in
      many countries. The contributing factors associated with LR are controversial and
      poorly defined. We hypothesized that these factors might be better identified by
      analysing patients starting dialysis in three distinct European countries within
      the same area. METHOD: The referral and progression of kidney failure patterns
      were analysed with demographic, clinical and biological data in 279 non-selected
      consecutive patients starting dialysis in eight centres of three adjacent regions
      in France, Italy and Switzerland. RESULTS: Early referral (>6 months before the
      start of dialysis) was seen in 200 patients (71.6%), intermediate referral (1-6
      months) in 42 (15.1%) and LR (<1 month) in 37 (13.3%). However inter-centre
      variations were between 2 and 19% for LR and 6-50% for combined late and
      intermediate referral. There were no differences at the national levels, but LR
      was more frequent in the large city centres than in the private or regional
      structures, with 31 out of 169 (18.3%), two out of 55 (5.4%) and four out of 55
      (7.3%), respectively, of their patients (P<0.01). By multivariate analysis, it
      appears that, besides the presence of an active cancer and the CKD progression
      rate, the centre structure and the referring physician (primary care physicians
      and nephrologists are less responsible for LR than other medical specialists)
      play a significant role in the practice of LR. CONCLUSIONS: Within a dialysis
      cohort spread over adjacent regions of three countries, LR has the same global
      distribution pattern, indicating that different health and social security
      systems do not play a major role in inducing or preventing this practice. The
      contributing factors for LR that were identified are the type of the referring
      physician and the structure of the dialysis unit. Both factors are potential
      targets for an educational and collaborative approach.

PMID- 15252155
TI  - Statin use after renal transplantation: a systematic quality review of trial
      based evidence.
AB  - BACKGROUND AND OBJECTIVES: HMG-CoA reductase inhibitor (statin) therapy reduces
      cardiovascular risk in the general population and may modulate rejection in solid
      organ transplant recipients. We assessed whether current clinical evidence
      supports the use of statins to improve cardiac and/or renal outcomes after kidney
      transplantation. METHODS: We performed a systematic review of randomized,
      controlled intervention trials of statins among renal allograft recipients.
      Clinical trials published between January 1, 1993 and January 1, 2004 were
      identified by systematic search of electronic databases. Eligible studies
      measured the impact of therapy on acute allograft rejection, surrogates of
      cardiovascular risk and/or cardiovascular morbidity and mortality. We abstracted
      descriptive summaries of trial design elements and primary effect estimates, and
      assessed trial quality with a standardized quality evaluation tool. RESULTS:
      Thirteen eligible trials were identified. Statin therapy was associated with less
      acute allograft rejection in two early studies but was ineffective in three
      subsequent, larger trials. Therapeutic benefit was also seen in six of seven
      small studies that evaluated cardiovascular risk surrogates. Statin use did not
      significantly alter the primary composite outcome in a single large cardiac
      events trial, but was associated with reductions in secondary end-points of
      cardiac death analysed alone or with myocardial infarction. Important design
      distinctions included statin preparation and dose, concomitant interventions,
      study power and randomization methods. Median total quality scores were 52 for
      the rejection trials, 41 for the studies of cardiovascular risk surrogates and 69
      for the cardiac events trial, and showed a trend towards variation by outcome
      measure (P = 0.05). CONCLUSIONS: Heterogeneous study designs and methodological
      quality contribute to discrepant conclusions on the benefit of statin therapy to
      renal allograft recipients. Trial-based clinical evidence does not support the
      use of statins to lower acute rejection risk after kidney transplantation, but
      does indicate effectiveness for improvement in cardiovascular risk markers and
      possibly for reduction of clinical cardiac events.

PMID- 15252156
TI  - Dual blockade of the renin-angiotensin system compared with a 50% increase in the
      dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood
      pressure.
AB  - BACKGROUND: Several publications in the past 2 years have demonstrated that
      combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II
      receptor antagonist (AIIRA) are more effective in reducing blood pressure and
      proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This
      study compares the effect of increasing the ACEI dose by 50% with that of adding
      an AIIRA to a standard ACEI dose. METHODS: This study was designed as part of a
      previous comparison of ACEI with ACEI plus candesartan. Directly after completion
      of the randomized intervention periods of that study, the dose of ACEI was
      increased by 50% in all patients. Proteinuria and blood pressure were compared in
      both groups of patients in the three periods, on standard ACEI, on ACEI plus
      candesartan and on a dose of ACEI increased by 50%. RESULTS: No significant
      differences in the primary end-point proteinuria or secondary end-points were
      observed when the ACEI dose was increased by 50%. Proteinuria was 1.8 g in 24 h
      on candesartan and ACEI and 2.4 g in 24 h when the ACEI dose was increased by 50%
      (P<0.02). Systolic blood pressure was 126.6 mmHg on candesartan and ACEI and
      134.47 mmHg when the ACEI dose was increased by 50% (P<0.002). Diastolic blood
      pressure, serum creatinine, urea and potassium were not different between groups.
      CONCLUSIONS: Standard ACEI plus candesartan is more effective in reducing
      systolic blood pressure and proteinuria than a 50% increase in ACEI dose. This
      has implications for the prevention of renal failure in chronic renal disease.

PMID- 15252157
TI  - Effect of chronic tetrahydrobiopterin supplementation on blood pressure and
      proteinuria in 5/6 nephrectomized rats.
AB  - BACKGROUND: Tetrahydrobiopterin (BH4) is a key cofactor of nitric oxide (NO)
      synthase. Reduced BH4 levels may mediate endothelial NO synthase uncoupling,
      resulting in reduced NO synthesis and enhanced oxidative stress. In rats after
      5/6 nephrectomy (Nx), administration of BH4 prevents the onset of hypertension,
      typically observed 10 days after Nx. This effect is associated with an increased
      synthesis of NO. The aim of the present study was to evaluate the effect of
      chronic BH4 therapy on blood pressure and renal morphology. METHODS: During an 8
      week period, five groups of rats were studied: untreated 5/6 Nx rats, BH4-treated
      Nx rats (BH4, 10 mg/kg body weight/day administered intraperitoneally), l
      arginine treated Nx rats (LA, 130 mg/kg/day), diltiazem-treated Nx rats (DILT, 30
      mg/kg/day) and sham-operated rats. Treatments were commenced 24 h after surgery.
      Systolic blood pressure values (SBP), 24 h proteinuria (UP) and creatinine
      clearance rate (CCR) were assessed before and at weeks 4 and 8 of the study
      period. Histological changes in the kidney were evaluated at the end of the study
      (week 8). RESULTS: Compared with baseline, in Nx rats both SBP and UP increased
      significantly (112+/-1 to 136+/- 1.4 mmHg, P<0.01 and 23+/-2 to 127 +/- 26
      mg/day, P<0.01, respectively). Treatment with BH4 normalized SBP values as did
      treatment with LA and DILT (109+/-3, 115+/-2 and 114+/-2 mmHg, respectively). UP
      was markedly reduced by BH4, the reduction being similar to that obtained by LA
      and significantly more marked than that of DILT rats (20+/-2, 28+/-3 and 62+/- 14
      mg/day, respectively). CCR was equally decreased in all Nx groups. Histological
      evaluation showed the development of mesangial expansion in Nx rats, an effect
      that was significantly blunted by all treatments. CONCLUSIONS: In rats after 5/6
      nephrectomy, BH4 supplementation initiated 24 h after surgery and maintained for
      8 weeks preserved SBP, reduced UP and prevented the development of glomerular
      mesangial expansion.

PMID- 15252158
TI  - Assessment of body composition by dual energy X-ray absorptiometry, skinfold
      thickness and creatinine kinetics in chronic kidney disease patients.
AB  - BACKGROUND: Finding a method that can be routinely used to assess body
      composition with minimum error is still a challenge for those who work with
      chronic kidney disease (CKD) patients. This study aimed to compare the value of
      two surrogate techniques, skinfold thickness (SKF) and creatinine kinetics (CK)
      with dual energy X-ray absorptiometry (DEXA) as the reference method for
      measuring body fat and fat-free mass in non-dialysed CKD patients. METHODS: The
      body fat and fat-free mass of 50 non-dialysed CKD patients (38 male, 12 female)
      were measured by DEXA and compared with measurements obtained by SKF and CK.
      RESULTS: The mean values of body fat and fat-free mass obtained by SKF and CK
      differed significantly from measurements made by DEXA. The intra-class
      correlation coefficient (r) for body fat between SKF and DEXA (r = 0.74) and
      between CK and DEXA (r = 0.47) indicated a moderate degree of reproducibility. A
      Bland and Altman plot analysis showed a better agreement between SKF and DEXA
      [5.8 +/- 3.9% (-2.0 to 13.6)] than between CK and DEXA [8.8 +/- 8.8% (-8.8 to
      26.4)]. Regarding fat-free mass, the intra-class correlation coefficient (r)
      between SKF and DEXA (r = 0.85) indicated a good degree of reproducibility, while
      that between SKF and CK (r = 0.57) indicated a moderate degree of
      reproducibility. The Bland and Altman plot analysis for fat-free mass showed that
      DEXA agreed better with SKF [-3.1 +/- 3.4 kg (-9.9 to 3.7)] than with CK [-5.5 +/
      6.4 kg (-18.2 to 7.3)]. CONCLUSION: Skinfold thickness seems to be the method of
      choice for evaluating body fat. The limitations inherent to DEXA in evaluating
      fat-free mass makes it difficult to designate an alternate method of choice for
      assessing this body compartment.

PMID- 15252159
TI  - Measurement of circulating troponin Ic enhances the prognostic value of C
      reactive protein in haemodialysis patients.
AB  - BACKGROUND: Cardiac Troponin I (cTnI) levels are considered an important
      diagnostic tool in acute coronary events. They could be of predictive value in
      haemodialysis (HD) patients. However, the relationship between cTnI and the HD
      induced inflammatory state remains unclear. The aim of this study was to explore
      the prognostic relevance to all-cause and cardiovascular mortalities in HD
      patients of cTnI, in combination with highly sensitive C-reactive protein (hs
      CRP) levels. METHODS: We measured cTnI and hs-CRP at baseline (March 10 to
      November 16, 2001) in 191 HD patients without clinical signs of acute coronary
      artery disease [median age 66.7 years (range 22.3-93.5), 94 females, 97 males].
      We used a cTnI concentration with a total imprecision of 10% (0.03 microg/l),
      determined in the laboratory, as the analytical threshold value. Patients were
      followed for mortality until 1 January, 2003 (median follow-up 418 days). The
      adjusted relative risks (RRs) of death and 95% confidence intervals (CIs) were
      estimated using Cox proportional hazard models. RESULTS: A significant proportion
      (25.1%) of patients had elevated CTnl, > or =0.03 microg/l; 40.3% of patients had
      CRP concentrations > or =10 mg/l. During follow-up, 29 patients died, 44.8% due
      to cardiac causes. Elevated cTnI or CRP levels were associated with increased
      mortality [RR adjusted for age, sex and duration of dialysis 4.2 (1.9-9.0) for
      cTnI > or =0.03 microg/l and 3.6 (1.6-8.1) for CRP > or =10 mg/l], cTnI being
      particularly predictive of cardiovascular death. Moreover, the combination of
      elevated hs-CRP (> or =10 mg/l) and circulating cTnI (> or =0.03 microg/l)
      dramatically impaired the HD survival rate [adjusted RR for all-cause mortality
      16.9 (4.5-63.8)]. CONCLUSION: Circulating cTnI was associated with poor
      prognosis, especially when combined with elevated CRP, strongly supporting the
      adoption of regular cTnI testing in HD patients.

PMID- 15252160
TI  - Timing of first cannulation and vascular access failure in haemodialysis: an
      analysis of practice patterns at dialysis facilities in the DOPPS.
AB  - BACKGROUND: Optimal waiting time before first use of vascular access is not
      known. METHODS: Two practices-first cannulation time for fistulae and grafts, and
      blood flow rate-were examined as potential predictors of vascular access failure
      in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure
      (defined as time to first failure or first salvage intervention) was modelled
      using Cox regression. RESULTS: Among 309 haemodialysis facilities, 2730 grafts
      and 2154 fistulae were studied. For grafts, first cannulation typically occurred
      within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities.
      For fistulae, first cannulation occurred <2 months after placement in 36% of US,
      79% of European and 98% of Japanese facilities. Overall, the relative risk (RR)
      of graft failure in Europe was lower compared with the USA (RR = 0.69, P = 0.04).
      The RR of graft failure (reference group = first cannulation at 2-3 weeks) was
      0.84 with first cannulation at <2 weeks (P = 0.11), 0.94 with first cannulation
      at 3-4 weeks (P = 0.48) and 0.93 with first cannulation at >4 weeks (P = 0.48).
      The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P = 0.08),
      0.91 at 2-3 months (P = 0.43) and 0.87 at >3 months (P = 0.31) (reference group =
      first cannulation at 1-2 months). Facility median blood flow rate was not a
      significant predictor of access failure. CONCLUSIONS: Earlier cannulation of a
      newly placed vascular access at the haemodialysis facility level was not
      associated with increased risk of vascular access failure. Potential for
      confounding due to selection bias cannot be excluded, implying the importance of
      clinical judgement in determining time to first use of vascular access.

PMID- 15252161
TI  - Metabolic effects of amino acid solutions infused for renal protection during
      therapy with radiolabelled somatostatin analogues.
AB  - BACKGROUND: Infusion of amino acids (AAs) can reduce renal uptake of
      radiolabelled somatostatin analogues resulting in a lower kidney exposure during
      peptide radiotherapy of patients with neuroendocrine tumours. In this study, we
      investigated the metabolic effects related to the infusion of large amounts of
      amino acids in patients undergoing positron emission tomography (PET) studies
      with [(86)Y]DOTA(0)-D-Phe(1)-Tyr(3)-octreotide. METHODS: Twenty-four patients, in
      four consecutive groups of six, received a 4 h infusion of 120 g of mixed AAs
      and, in addition, either a 4 h infusion of 50 g of L-lysine (n = 6), a 10 h
      infusion of 240 g of mixed AAs (n = 6), a 4 h infusion of 50 g of L-lysine + L
      arginine (Lys-Arg; n = 6) or no infusion (control; n = 6) in randomly ordered
      crossover studies. A number of clinical and biochemical parameters in blood and
      urine were measured over 24 h, including calculation of creatinine clearance,
      tubular reabsorption of inorganic phosphate (TRP) and fractional urate excretion.
      RESULTS: No clinical side effects occurred during the infusions except for nausea
      and vomiting under mixed AAs. Patients in the latter group showed an increase in
      serum urea, whereas patients receiving L-lysine showed an increase in serum
      potassium and chloride. Inorganic phosphate levels dropped at 2.5 h in all groups
      except controls, and a significant decrease in TRP was observed with mixed AAs
      but not with L-lysine or Lys-Arg. CONCLUSION: Although infusion of AA solutions
      can improve the effect of therapy by allowing the administration of higher doses
      of radiolabelled somatostatin analogues, each preparation has specific sides
      effects that should be taken into account with this type of therapy.

PMID- 15252162
TI  - Association between cardiovascular autonomic neuropathy and left ventricular
      hypertrophy in diabetic haemodialysis patients.
AB  - BACKGROUND: Patients with diabetic nephropathy are likely to have neurological
      complications including cardiovascular autonomic dysfunction, which is related to
      increased risk of mortality. We investigated whether cardiovascular autonomic
      neuropathy is associated with left ventricular hypertrophy (LVH) in diabetic
      haemodialysis patients. METHODS: Holter electrocardiography was carried out for
      24 h with time and frequency domain analyses of heart rate variability in 154
      diabetic (age 62+/-11 years) and 63 non-diabetic haemodialysis patients (62+/-10
      years). The left ventricular mass index (LVMI) was determined by
      echocardiography. We used the percentage of differences exceeding 50 ms between
      adjacent normal RR intervals (pNN50) in time domain analysis and the power in the
      high-frequency range (HF: 0.15-0.40 Hz) in frequency domain analysis as
      indicators of parasympathetic activity. RESULTS: The mean LVMI was greater in
      diabetic than in non-diabetic patients (168+/-63 vs 144+/-54 g/m(2), P<0.01).
      LVMI inversely correlated with pNN50 (r = -0.270, P = 0.0007, n = 154) and HF (r
      = -0.277, P = 0.0005, n = 154) in diabetic patients, but not in non-diabetic
      patients. By multiple logistic analysis, LVH was strongly associated with pNN50
      (odds ratio 0.088; 0, <2%; 1, >/=2%) and HF (odds ratio 0.058; 0, <500 ms(2); 1,
      >/=500 ms(2)) in diabetic patients. CONCLUSIONS: Impaired parasympathetic
      activity, which indicates cardiovascular autonomic neuropathy, was associated
      with the presence of LVH in diabetic haemodialysis patients. The co-existence of
      cardiovascular autonomic neuropathy and LVH may be one of the key factors for the
      high incidence of cardiovascular events in diabetic haemodialysis patients.

PMID- 15252163
TI  - Natural history of vascular calcification in dialysis and transplant patients.
AB  - BACKGROUND: The purpose of the present study was to determine the natural history
      of coronary artery and aorta calcification by spiral computed tomography (CT) in
      patients who undergo a renal transplant and patients on haemodialysis. METHODS:
      Two cohorts were evaluated for the natural history of vascular calcification: (i)
      23 patients who underwent a baseline CT scan at the time of renal transplant and
      a repeat evaluation 15-20 months later; and (ii) 33 chronic kidney disease, stage
      5 haemodialysis subjects who underwent a baseline CT scan, all followed for a
      minimum of 15 months, and 17 of whom underwent a second CT scan. RESULTS: In the
      patients undergoing a renal transplant, there was no net change in CAC with time,
      suggesting stabilization of calcification. In the haemodialysis patients, the
      median CAC increased by 1.27+/-1.88 score/days, P = 0.013. There was a trend
      towards increasing AoC score in both groups. All patients without calcification
      at baseline remained calcification free at follow-up. In the 15 months following
      baseline, the six dialysis patients who died had a significantly greater CAC
      score at baseline compared with the 24 patients who remained alive. Similarly,
      those patients who were hospitalized had a greater baseline CAC than patients who
      were not hospitalized. CONCLUSION: In this preliminary study, renal
      transplantation appears to slow down or arrest CAC, whereas CAC progresses in
      haemodialysis patients. In haemodialysis patients, CAC was greater in patients
      who died or were hospitalized compared with those who remained alive or were not
      hospitalized.

PMID- 15252164
TI  - Polyneuropathy in the diabetic patient--update on pathogenesis and management.

PMID- 15252166
TI  - An increased polymeric IgA level is not a prognostic marker for progressive IgA
      nephropathy.
AB  - BACKGROUND: Elution of IgA from renal biopsies of patients with primary IgA
      nephropathy (IgAN) has suggested that mesangial IgA deposits are mainly
      multimeric in nature. This macromolecular IgA consists of dimeric and polymeric
      IgA and may be derived from the circulation. In children with IgAN, circulating
      macromolecular IgA levels correlate with bouts of macroscopic haematuria, but in
      adults a correlation with disease activity is less clear. Therefore, we have
      designed a novel method to assess the levels of polymeric IgA (pIgA) in sera from
      patients and controls. METHODS: A novel precipitation assay using recombinant
      CD89 was developed to measure pIgA. Polymeric IgA levels were measured in serum
      samples obtained from healthy volunteers (n = 21) and patients with IgAN (n =
      51). Subsequently, serum pIgA levels were correlated with clinical parameters of
      disease. RESULTS: Serum pIgA levels were significantly increased in patients with
      IgAN. However, pIgA concentrations relative to total IgA were significantly lower
      in sera of patients with IgAN. No correlation was found between serum pIgA levels
      and clinical parameters of IgAN, such as decline of glomerular filtration rate,
      haematuria or proteinuria. CONCLUSIONS: Although absolute levels of serum pIgA
      are increased in patients with IgAN as compared with controls, levels of pIgA
      relative to total serum IgA are lower. No significant correlation was found
      between serum concentrations of pIgA and clinical parameters of disease. These
      data support the notion that it is not the size alone, but the physicochemical
      composition of the macromolecular IgA that is the key factor leading to mesangial
      deposition.

PMID- 15252165
TI  - Inhibition of brush border dipeptidase with cilastatin reduces toxic accumulation
      of cyclosporin A in kidney proximal tubule epithelial cells.
AB  - BACKGROUND: Cilastatin reduces nephrotoxicity associated with cyclosporin A (CyA)
      in solid organ and bone marrow transplantation. This appears to be unrelated to
      changes in renal haemodynamics or CyA metabolism. How cilastatin induces this
      protection is unclear, but it could result from changes on accumulation of CyA
      proximal cells. METHODS: We investigated the effects of cilastatin on primary
      cultures of pig kidney proximal tubule epithelial cells (PTECs) treated with CyA
      and FK506. Cell membrane fluidity and membrane-bound cholesterol-rich raft (MBCR)
      distribution were evaluated by fluorescence microscopy, and CyA transport by
      radioimmunoassay. Changes in CyA- and FK506-induced apoptosis were also evaluated
      by electron and light microscopy, flow cytometry, and detection of cytoplasmic
      nucleosones by enzyme-linked immuosorbent assay. RESULTS: CyA caused a dose
      dependent reduction of cell membrane fluidity, which was prevented by pre
      treating PTECs with cilastatin. Cilastatin also inhibited CyA transport across
      membranes and reduced recovery of CyA in mitochondria and membrane-bound
      fractions from cilastatin-treated PTECs. This effect was not related to an
      altered distribution of MBCRs, which are essential for CyA transport. Cilastatin
      protected against CyA- and FK506-induced apoptosis. CONCLUSIONS: Prevention of
      CyA-induced reduction of cell membrane fluidity and inhibition of CyA transport
      are features of cilastatin's direct effects on PTECs. Unaltered distribution of
      MBCRs in the presence of cilastatin suggests that cilastatin binding to raft
      bound dipeptidases, rather than MBCR modifications, causes interference with CyA
      transport. These results provide additional insight into the mechanisms and scope
      of cilastatin nephroprotection.

PMID- 15252168
TI  - Restoring glutathione as a therapeutic strategy in chronic kidney disease.

PMID- 15252167
TI  - Perceived mental health at the start of dialysis as a predictor of morbidity and
      mortality in patients with end-stage renal disease (CALVIDIA Study).
AB  - BACKGROUND: Health-related quality of life may affect morbidity and survival in
      end-stage renal disease, but it is not clear whether coexisting comorbidity and
      other known prognostic variables could account for such an association. METHODS:
      To study the relationship between health-related quality of life and morbidity
      and survival, we carried out an inception cohort study in patients starting
      chronic dialysis, mostly diabetics, with a follow-up of 1-3 years in 34 Spanish
      hospitals. Health-related quality of life was measured by the SF-36 Health Survey
      and Karnofsky scale. Charlson age-comorbidity index and other prognostic clinical
      variables were measured concurrently. The primary outcome variable was time until
      death and the secondary outcome was hospitalization days. RESULTS: Of 318
      patients enrolled (208 diabetics), with a median follow-up of 771 days, 80 died.
      In the unadjusted analysis, all-cause mortality was associated with lower SF-36
      physical and mental component scores and Karnofsky scale. In the adjusted
      analysis, SF-36 mental component score predicted all-cause mortality (hazard
      ratio for a 10 point decrease: 1.28; 95% confidence interval: 1.05-1.56). The SF
      36 mental component score also predicted more hospitalization days (adjusted risk
      ratio of each additional hospital day associated with every 10 point decrease:
      1.25; 95% confidence interval: 1.08-1.45). Among diabetics, both the SF-36
      physical and mental components predicted mortality and hospitalization days.
      CONCLUSIONS: In end-stage renal disease, perceived mental health is an
      independent predictor of mortality and morbidity, mainly among diabetics
      patients.

PMID- 15252169
TI  - Homocysteine induced impairment of nitric oxide-dependent vasorelaxation is
      reversible by the superoxide dismutase mimetic TEMPOL.
AB  - BACKGROUND: Elevated plasma homocysteine concentrations in renal patients are
      associated with accelerated cardiovascular disease. The mechanism(s) by which
      homocysteine acts remains unclear however, evidence implicates a role involving
      endothelial dysfunction. METHODS: Rat femoral arteries after acute or 4-h pre
      incubation with racemic D,L-homocysteine (100 microM) were mounted on a myograph,
      pre-constricted with phenylephrine (10 microM) and responses to acetylcholine
      dependent vasorelaxation examined. The incubations were repeated in the presence
      of indomethacin (10 microM), omega-nitro-L-arginine methyl ester (100 microM), L
      arginine (100 microM), tetrahydrobiopterin (1 microM), catalase (1200 U/ml),
      ebselen, a peroxynitrite chelator (20 microM) and TEMPOL, a superoxide dismutase
      mimetic (1 mM). Results are shown as means+/-standard error, expressed as per
      cent relaxation to acetylcholine added (nmol/l). RESULTS: Increasing
      concentrations of homocysteine had no affect when added directly to basally
      relaxed or pre-constricted freshly isolated vessels. However, 4-h pre-incubation
      with or without homocysteine significantly shifted the acetylcholine EC(50)
      (EC(50) was defined as the concentration of acetylcholine that caused relaxation
      of the phenylephrine contracted tissue by 50%), control((4 h)) = 74.7 nmol/l+/
      10.5 vs 100 microM D,L-homocysteine((4 h)) = 159.9 nmol/l+/-20.6; P<0.05) without
      affecting maximal relaxation. Response to endothelial independent relaxation was
      unaffected. Indomethacin, indomethacin and omega-nitro-L-arginine methyl ester, l
      arginine and tetrahydrobiopterin, catalase and ebselen had no effect on the
      EC(50) in homocysteine-exposed arteries. However, TEMPOL normalized
      vasorelaxation in homocysteine-treated arteries (75.2 nmol/l+/-14.6) but had no
      effect on the 4-h control group. Moreover, washing TEMPOL from the treated
      vessels restored endothelial dysfunction in D,L-homocysteine-treated vessels
      (163.9 nmol/l+/-34.1). CONCLUSIONS: We conclude that homocysteine causes
      endothelial dysfunction by up-regulating a potential superoxide generating system
      resulting in reduced nitric oxide bio-availability.

PMID- 15252170
TI  - Insulin resistance and pancreatic beta-cell function in patients with
      hypertensive kidney disease.
AB  - BACKGROUND: Insulin resistance and hyperinsulinaemia have been reported among
      patients with chronic renal failure. However, little is known concerning insulin
      sensitivity among patients with hypertensive kidney disease (HKD), especially in
      those with moderate or severe renal dysfunction. METHODS: We examined and
      compared 30 patients with HKD, 30 normotensive patients with chronic kidney
      disease (CKD-NT), 30 normal controls and 30 patients with hypertension and normal
      renal function (HTN). Moderate and severe renal dysfunction were defined
      according to the K/DOQI definitions (estimated glomerular filtration rates
      between 15 and 59 ml/min per 1.73 m(2)). The homeostasis model assessment of
      insulin resistance (HOMA-R) and three surrogate indexes based on 75 g oral
      glucose tolerance test results were used to determine insulin sensitivity.
      RESULTS: A trend to higher HOMA-R values in the HTN and HKD groups than in the
      other groups was noted, but the difference was not statistically significant. The
      insulin sensitivity index (ISI) proposed by Stumvoll et al. was significantly
      lower in the HTN, HKD and CKD-NT groups than in controls and was significantly
      lower in HKD than in the HTN and CKD-NT groups. The insulin sensitivity index
      proposed by Gutt et al. was significantly lower in HKD than in the control and
      HTN groups and showed a trend to being lower in HKD than in CKD-NT. The same
      patterns prevailed in the oral glucose ISI. We assumed that subjects whose ISI
      values decreased below the mean value minus 2-SD in the control group manifest
      apparent insulin resistance. According to this criterion, approximately 40% of
      HKD subjects were in an insulin-resistant state: only <10% of HTN subjects and
      approximately 10-30% of CKD-NT subjects were insulin resistant. CONCLUSIONS: HKD
      with moderate to severe renal dysfunction is associated with insulin resistance.

PMID- 15252171
TI  - High prevalence in Switzerland of pure red-cell aplasia due to anti
      erythropoietin antibodies in chronic dialysis patients: report of five cases.
AB  - BACKGROUND: Pure red-cell aplasia (PRCA) after erythropoietin (Epo)
      administration due to the appearance of neutralizing anti-Epo antibodies has been
      reported in over 200 cases between 1998 and 2002. However, large intercountry
      disparities were observed in the occurrence of this syndrome. METHODS: On behalf
      of the Swiss Society of Nephrology, a survey was conducted in all the dialysis
      units of Switzerland in order to collect information on the occurrence,
      diagnostic and evolution data of the cases observed. A questionnaire was send to
      the nephrologists in charge of each of the 69 dialysis units in January 2003. The
      clinical and biological data of the suspected cases were analysed and compared
      with the data provided to health authorities and pharmaceutical companies.
      RESULTS: A total of five cases were identified as true PRCA with demonstrated
      positive anti-Epo antibodies. They occurred between November 1998 and February
      2002, were all treated by haemodialysis and had received Epo subcutaneously. The
      median appearance time of refractory anaemia after Epo initiation was 10 months
      (range: 7-54 months). Two cases had been treated exclusively with epoietin-alpha,
      one solely with epoietin-beta and the two others with a combination of both. With
      five cases out of a total of about 2500 dialysis patients and 2300 Epo-treated
      dialysis patients or an exposure rate to Epo of 9900 dialysis patient-years
      during a 4.3 year period, this prevalence is among the highest of those reported
      in European countries. CONCLUSIONS: The prevalence of PRCA after Epo
      administration in dialysis patients appears particularly high in Switzerland.
      Among the potential explanations, the most plausible are the high percentage of
      dialysis patients treated with Epo, the almost exclusive subcutaneous
      administration, the larger market distribution of the epoietin-alpha brand, the
      eventual disruption of the cold chain and the setting-up of a systematic national
      survey.

PMID- 15252172
TI  - Severe hypernatraemia (221 mEq/l), rhabdomyolysis and acute renal failure after
      cerebral aneurysm surgery.

PMID- 15252173
TI  - Rapid improvement of calciphylaxis after intravenous pamidronate therapy in a
      patient with chronic renal failure.

PMID- 15252174
TI  - Four cases of pure red cell aplasia secondary to epoetin beta, with strong
      temporal relationships.

PMID- 15252175
TI  - Successful re-introduction of recombinant human erythropoietin following antibody
      induced pure red cell aplasia.

PMID- 15252176
TI  - A rare cause of fever associated with leukopenia in a renal transplant patient.

PMID- 15252177
TI  - Underestimated complications in thrombotic thrombocytopenic purpura--haemolytic
      uraemic syndrome.

PMID- 15252178
TI  - Apricot urine in autumn.

PMID- 15252179
TI  - An unrecognized cause of oedema in a patient with lupus nephritis: protein losing
      enteropathy.

PMID- 15252180
TI  - Calcification of end-stage renal allograft in a peritoneal dialysis patient.

PMID- 15252181
TI  - Bone mineral density, biochemical markers and skeletal fractures in haemodialysis
      patients.

PMID- 15252182
TI  - Combination pegylated interferon and ribavirin therapy precipitating acute renal
      failure and exacerbating IgA nephropathy.

PMID- 15252183
TI  - Effect of renal failure and dialysis on circulating ghrelin concentration in
      children.

PMID- 15252184
TI  - Colestimide co-administered with atorvastatin attenuates the progression of
      vascular calcification in haemodialysis patients.

PMID- 15252185
TI  - Combination of intermittent haemodialysis and high-volume continuous
      haemofiltration for the treatment of severe metformin-induced lactic acidosis.

PMID- 15252186
TI  - Neutropenia associated with the use of low-dose methotrexate in a peritoneal
      dialysis patient.

PMID- 15252187
TI  - Erythroid-induced commitment of K562 cells results in clusters of differentially
      expressed genes enriched for specific transcription regulatory elements.
AB  - Understanding regulation of fetal and embryonic hemoglobin expression is
      critical, since their expression decreases clinical severity in sickle cell
      disease and beta-thalassemia. K562 cells, a human erythroleukemia cell line, can
      differentiate along erythroid or megakaryocytic lineages and serve as a model for
      regulation of fetal/embryonic globin expression. We used microarray expression
      profiling to characterize transcriptomes from K562 cells treated for various
      times with hemin, an inducer of erythroid commitment. Approximately 5,000 genes
      were expressed irrespective of treatment. Comparative expression analysis (CEA)
      identified 899 genes as differentially expressed; analysis by the self-organizing
      map (SOM) algorithm clustered 425 genes into 8 distinct expression patterns, 322
      of which were shared by both analyses. Differential expression of a subset of
      genes was validated by real-time RT-PCR. Analysis of 5'-flanking regions from
      differentially expressed genes by PAINT v3.0 software showed enrichment in
      specific transcription regulatory elements (TREs), some localizing to different
      expression clusters. This finding suggests coordinate regulation of cluster
      members by specific TREs. Finally, our findings provide new insights into rate
      limiting steps in the appearance of heme-containing hemoglobin tetramers in these
      cells.

PMID- 15252188
TI  - Functional evaluation of human ClC-2 chloride channel mutations associated with
      idiopathic generalized epilepsies.
AB  - The ClC-2 Cl- channel has been postulated to play a role in the inhibitory GABA
      response in neurons or to participate in astrocyte-dependent extracellular
      electrolyte homeostasis. Three different mutations in the CLCN2 gene, encoding
      the voltage-dependent homodimeric ClC-2 channel, have been associated with
      idiopathic generalized epilepsy (IGE). We study their function in vitro by patch
      clamp and confocal microscopy in transiently transfected HEK-293 cells. A first
      mutation predicts a premature stop codon (M200fsX231). An altered splicing, due
      to an 11-bp deletion in intron 2 (IVS2-14del11), predicts exon 3 skipping
      (Delta74-117). A third is a missense mutation (G715E). M200fsX231 and Delta74-117
      are nonfunctional and do not affect the function of the normal (wild type, WT)
      channel. Neither M200fsX231 nor Delta74-117 reach the plasma membrane. Concerning
      the IVS2-14del11 mutation, we find no difference in the proportion of exon
      skipped to normally spliced mRNA using a minigene approach and, on this basis,
      predict no alteration in channel expression in affected individuals. G715E has
      voltage dependence and intracellular Cl- dependence indistinguishable from WT
      channels. ClC-2 channels are shown to be sensitive to intracellular replacement
      of ATP by AMP, which accelerates the opening and closing kinetics. This effect is
      diminished in the G715E mutant and not significant in WT+G715E coexpression. We
      do not know whether, in a situation of cellular ATP depletion, this might become
      pathological in individuals carrying the mutation. We postulate that loss of
      function mutation M200fsX231 of ClC-2 might contribute to the IGE phenotype
      through a haploinsufficiency mechanism.

PMID- 15252189
TI  - Multigenic control of serum adiponectin levels: evidence for a role of the APM1
      gene and a locus on 14q13.
AB  - Adiponectin is a circulating enhancer of insulin action that is secreted by the
      adipose tissue. In epidemiological studies, serum levels of this protein predict
      the risk of type 2 diabetes and cardiovascular events. Serum adiponectin levels
      have been associated with variants at the adiponectin (APM1) and PPARgamma2 loci
      and have also been linked to markers on 5p15 and 14q13. We investigated the role
      of these four loci in regulating serum adiponectin in a Caucasian population from
      Italy. Four haplotype-tagging single-nucleotide polymorphisms (ht-SNPs) (-11377
      C>G, -4041 A>C, +45 T>G, and +276 G>T) at the APM1 locus and the PPARgamma2
      Pro12Ala polymorphism were examined for association with serum adiponectin in 413
      unrelated, nondiabetic individuals. Of the five SNPs tested, +276G>T was the only
      one to be associated with serum adiponectin (P = 0.032), with "TT" individuals
      having higher adiponectin levels than other subjects. In a variance-components
      analysis of 737 nondiabetic members of 264 nuclear families, adiponectin
      heritability was 30%, with a small but significant proportion explained by the
      +276 genotype ( P = 0.0034). Suggestive evidence of linkage with adiponectin
      levels was observed on chromosome 14q13, with a LOD of 2.92 (P = 0.000057) after
      including the APM1 +276 genotype in the model. No linkage was observed at 5p15.
      Our data indicate a strong genetic control of serum adiponectin. A small
      proportion of this can be attributed in our population to variability at the APM1
      locus, but an as yet unidentified gene on 14q13 appears to play a much bigger
      role.

PMID- 15252190
TI  - False-positive urine opiate screening associated with fluoroquinolone use.
AB  - OBJECTIVE: To review the literature regarding false-positive urine opiate screens
      associated with the use of fluoroquinolones. DATA SOURCES: Literature was
      identified using MEDLINE (1966-February 2004), EMBASE, and all EBM Reviews with
      the terms quinolones, substance abuse detection, opiates, cross-reactions, false
      positive reactions, and each fluoroquinolone. Article references were also
      reviewed. DATA SYNTHESIS: Various settings utilize the practice of screening for
      drugs of abuse, such as opiates. These screening procedures can impact aspects of
      one's life, such as employment; therefore, accuracy is of the utmost importance.
      Two clinical trials were evaluated which showed that certain fluoroquinolone
      antibiotics cross-react with some of the commonly used urine opiate screening
      immunoassays. This suggests the importance of verifying positive results in
      instances where one's livelihood can be affected. CONCLUSIONS: Fluoroquinolones
      can cause false-positive urine opiate screens. Clinicians should be aware of this
      potential interaction and may need to verify positive results.

PMID- 15252191
TI  - The effect of clarithromycin on inflammatory markers in chronic obstructive
      pulmonary disease: preliminary data.
AB  - BACKGROUND: Clarithromycin is an antimicrobial agent that can be used for
      treatment of chronic obstructive pulmonary disease (COPD) exacerbations with
      bronchodilator therapy. However, it has also been shown that clarithromycin has
      antiinflammatory effects by the inhibition of cytokine production. OBJECTIVE: To
      evaluate the antiinflammatory effect of clarithromycin on serum and sputum
      interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4
      levels in patients with COPD. METHODS: Thirty men with mild to moderate COPD were
      enrolled in this prospective, single-center, double-blind, placebo-controlled
      study. None of the patients was receiving systemic or inhaled corticosteroids
      during the study. Subjects received either clarithromycin or placebo for 14 days.
      Before and after this treatment period, spirometric tests and arterial blood gas
      analysis were performed, blood was drawn for measurement of serum inflammatory
      markers, and sputum was induced. RESULTS: There were no statistically significant
      differences in baseline clinical or laboratory parameters between the groups.
      After the treatment, the induced sputum total cell counts, and IL-8 and TNF-alpha
      levels decreased significantly in the clarithromycin group compared with
      pretreatment levels (mean +/- SD IL-8 1606 +/- 367.3 vs 882 +/- 143.6 pg/mL, p =
      0.001; TNF-alpha 638.2 +/- 287.5 vs 390 +/- 235 pg/mL, p = 0.001). Similarly,
      decreases in serum inflammatory markers were found in the clarithromycin group
      while there was no significant change in the placebo group. CONCLUSIONS: This
      study demonstrated that the decrease in IL-8 and TNF-alpha levels might be
      related to the antiinflammatory effect of clarithromycin. Thus, we suggest that
      the use of clarithromycin in COPD exacerbations may either treat the infection or
      help control the inflammation. Future studies are needed to determine the
      clinical significance of these findings.

PMID- 15252192
TI  - Soluble or insoluble prussian blue for radiocesium and thallium poisoning?
AB  - OBJECTIVE: To review the available English-language literature concerning the
      efficacy of soluble and insoluble Prussian blue used as a therapeutic agent in
      radiocesium and thallium poisoning. DATA SOURCES: A thorough search of MEDLINE,
      Toxline, and EMBASE databases (1960s-August 2003) was performed. Search terms
      included Prussian blue, thallium, and radiocesium poisoning. Bibliographies of
      relevant papers were reviewed for additional citations. study selection AND DATA
      EXTRACTION: Reports and studies of human trials and cases, along with animal and
      relevant in vitro data, were sought. Data were categorized as insoluble and
      soluble Prussian blue and by thallium and radiocesium poisoning. DATA SYNTHESIS:
      The majority of evidence describing the efficacy of Prussian blue for radiocesium
      poisoning is based on the use of the insoluble form. In contrast, the majority of
      data supporting the efficacy of Prussian blue in thallium poisoning involves the
      use of the soluble form. CONCLUSIONS: Insoluble Prussian blue has recently been
      approved in the US for treatment of both thallium and radiocesium poisoning.
      While there is sufficient evidence that the insoluble form of Prussian blue is
      effective in radiocesium poisoning, there is a paucity of analogous data
      supporting its use in thallium poisoning. Whether the physicochemical differences
      between soluble and insoluble Prussian blue have any effect on outcomes in human
      poisoning is not known.

PMID- 15252193
TI  - Clonazepam for treatment of sleep disturbances associated with combat-related
      posttraumatic stress disorder.
AB  - BACKGROUND: Clonazepam is widely used for the treatment of posttraumatic stress
      disorder (PTSD)-related sleep disturbances despite very limited published data
      supporting its use for this indication. OBJECTIVE: We conducted a pilot
      controlled trial to provide more data on this clinical practice and lay the
      foundation for more definitive studies. METHODS: The study was designed as a
      randomized, single-blind (ie, patient only), placebo-controlled, crossover
      clinical trial involving administration of clonazepam 1 mg at bedtime for one
      week followed by 2 mg at bedtime for one week. The following week served as a
      washout period before the alternate treatment was begun. Patients completed sleep
      diaries each morning upon awakening throughout the study. Parameters included
      quantity of sleep, quality of sleep, frequency and intensity of difficulty
      falling or staying asleep, and frequency and intensity of recurrent distressing
      dreams. RESULTS: Six patients with combat-related PTSD participated in the study.
      There were no statistically significant differences between clonazepam and
      placebo for any measure, although clonazepam therapy resulted in mild to moderate
      numeric improvements in difficulty falling or staying asleep. Adverse effects of
      clonazepam were generally mild and essentially indiscernible from those
      attributed to placebo. Only one patient elected to receive further treatment with
      clonazepam at the conclusion of the trial. CONCLUSIONS: Clonazepam therapy was
      largely ineffective in improving sleep disturbances, particularly nightmares,
      associated with combat-related PTSD. The small sample size was a significant
      limitation of this study, but the prospective design and single-blind, placebo
      control parameters were strengths. Further studies are needed to further define
      the role of this widespread clinical practice.

PMID- 15252194
TI  - Thyroid function alterations following quetiapine initiation in a developmentally
      disabled adolescent.

PMID- 15252195
TI  - Advising cancer patients on natural health products--a structured approach.
AB  - BACKGROUND: Many patients with cancer (45-60%) use natural health products
      (NHPs). Pharmacists often find it difficult to advise these patients effectively.
      OBJECTIVE: To explore pharmacists' perceptions of the information needed to
      advise cancer patients on NHPs and develop a structured counseling approach.
      METHODS: A qualitative study was conducted using a focus group of pharmacists
      from an integrated cancer care organization in Canada. The outcome measures were
      the definitions of and reasons for the information needed to advise patients on
      NHPs and a counseling approach using laymen terms. RESULTS: Eight focus group
      sessions took place, from which 6 categories of information emerged: role of the
      advisor, evaluation of evidence, assessment of efficacy, assessment of toxicity,
      monitoring parameters, and provision of a closure. A patient counseling approach
      was developed based on this information. CONCLUSIONS: The findings provided a
      description of and rationale for categories of information needed to advise
      cancer patients on NHPs. A structured, step-by-step approach to counseling these
      patients was developed.

PMID- 15252196
TI  - Intraoral application of atropine sulfate ophthalmic solution for clozapine
      induced sialorrhea.

PMID- 15252197
TI  - Evolutionary dynamics of tumor suppressor gene inactivation.
AB  - Tumor suppressor genes (TSGs) are important gatekeepers that protect against
      somatic evolution of cancer. Losing both alleles of a TSG in a single cell
      represents a step toward cancer. We study how the kinetics of TSG inactivation
      depends on the population size of cells and the mutation rates for the first and
      second hit. We calculate the probability as function of time that at least one
      cell has been generated with two inactivated alleles of a TSG. We find three
      different kinetic laws: in small, intermediate, and large populations, it takes,
      respectively, two, one, and zero rate-limiting steps to inactivate a TSG. We also
      study the effect of chromosomal and other genetic instabilities. Small lesions
      without genetic instability can take a very long time to inactivate the next TSG,
      whereas the same lesions with genetic instability pose a much greater risk for
      cancer progression.

PMID- 15252198
TI  - Older age becomes common late in human evolution.
AB  - Increased longevity, expressed as number of individuals surviving to older
      adulthood, represents one of the ways the human life history pattern differs from
      other primates. We believe it is a critical demographic factor in the development
      of human culture. Here, we examine when changes in longevity occurred by
      assessing the ratio of older to younger adults in four hominid dental samples
      from successive time periods, and by determining the significance of differences
      in these ratios. Younger and older adult status is assessed by wear seriation of
      each sample. Whereas there is significant increased longevity between all groups,
      indicating a trend of increased adult survivorship over the course of human
      evolution, there is a dramatic increase in longevity in the modern humans of the
      Early Upper Paleolithic. We believe that this great increase contributed to
      population expansions and cultural innovations associated with modernity.

PMID- 15252199
TI  - Host-parasite interactions and the evolution of ploidy.
AB  - Although the majority of animals and plants, including humans, are dominated by
      the diploid phase of their life cycle, extensive diversity in ploidy level exists
      among eukaryotes, with some groups being primarily haploid whereas others
      alternate between haploid and diploid phases. Previous theory has illuminated
      conditions that favor the evolution of increased or decreased ploidy but has shed
      little light on which species should be primarily haploid and which primarily
      diploid. Here, we report a discovery that emerged from host-parasite models in
      which ploidy levels were allowed to evolve: selection is more likely to favor
      diploidy in host species and haploidy in parasite species. Essentially, when
      parasites must evade a host's immune system or defense response, selection favors
      parasitic individuals that express a narrow array of antigens and elicitors, thus
      favoring haploid parasites over diploid parasites. Conversely, when hosts must
      recognize a parasite before mounting a defensive response, selection favors hosts
      with a broader arsenal of recognition molecules, thus favoring diploid hosts over
      haploid hosts. These results are consistent with the predominance of haploidy
      among parasitic protists.

PMID- 15252200
TI  - MotifPrototyper: a Bayesian profile model for motif families.
AB  - In this article, we address the problem of modeling generic features of
      structurally but not textually related DNA motifs, that is, motifs whose
      consensus sequences are entirely different but nevertheless share "metasequence
      features" reflecting similarities in the DNA-binding domains of their associated
      protein recognizers. We present MotifPrototyper, a profile Bayesian model that
      can capture structural properties typical of particular families of motifs. Each
      family corresponds to transcription regulatory proteins with similar types of
      structural signatures in their DNA-binding domains. We show how to train
      MotifPrototypers from biologically identified motifs categorized according to the
      TRANSFAC categorization of transcription factors and present empirical results of
      motif classification, motif parameter estimation, and de novo motif detection by
      using the learned profile models.

PMID- 15252201
TI  - Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated
      antibody and CD4(+) and CD8(+) T cell responses in humans.
AB  - NY-ESO-1 is a "cancer-testis" antigen expressed in many cancers. ISCOMATRIX is a
      saponin-based adjuvant that induces antibody and T cell responses. We performed a
      placebo-controlled clinical trial evaluating the safety and immunogenicity of
      recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant. Forty-six evaluable
      patients with resected NY-ESO-1-positive tumors received three doses of vaccine
      intramuscularly at monthly intervals. The vaccine was well tolerated. We observed
      high-titer antibody responses, strong delayed-type hypersensitivity reactions,
      and circulating CD8(+) and CD4(+) T cells specific for a broad range of NY-ESO-1
      epitopes, including known and previously unknown epitopes. In an unplanned
      analysis, vaccinated patients appeared to have superior clinical outcomes to
      those treated with placebo or protein alone. The vaccine is safe and highly
      potent immunologically.

PMID- 15252202
TI  - Attenuation control of pyrG expression in Bacillus subtilis is mediated by CTP
      sensitive reiterative transcription.
AB  - In Bacillus subtilis and other Gram-positive bacteria, pyrimidine-mediated
      regulation of the pyrG gene, which encodes CTP synthetase, occurs through an
      attenuation mechanism involving an intrinsic transcription terminator in the pyrG
      leader region. Low intracellular levels of CTP prevent termination at the
      attenuator by a mechanism that requires the nontemplate strand sequence GGGC at
      the pyrG transcription initiation site (first G =+1) and the leader transcript
      sequence GCUCCC located at the 5' end of the terminator RNA hairpin. In this
      study, we demonstrate that reiterative transcription adds G residues (up to at
      least 10) to the 5' end of pyrG transcripts when B. subtilis cells are starved
      for pyrimidines but not when cells are grown with excess cytidine. Regulated
      repetitive addition of G residues, as well as pyrimidine-mediated pyrG
      regulation, requires the sequence GGGC or GGGT at the start of pyrG
      transcription. Mutational insertion of four extra G residues at the 5' end of the
      pyrG transcript (i.e., 5'-GGGGGGGC) results in constitutive pyrG expression. We
      propose that the incorporation of extra G residues by reiterative transcription
      at the wild-type promoter occurs when normal transcription elongation is stalled
      at position +4 by low levels of the incoming substrate, CTP, during pyrimidine
      limitation. The poly(G) extensions on the 5' ends of pyrG transcripts act to
      prevent transcription attenuation by base pairing with the sequence CUCCCUUUC
      located in the 5' strand of the terminator hairpin. This control mechanism is
      likely to operate in other Gram-positive bacteria containing similar pyrG leader
      sequences.

PMID- 15252203
TI  - From the Cover: The dynamics of genomic-length DNA molecules in 100-nm channels.
AB  - We show that genomic-length DNA molecules imaged in nanochannels have an
      extension along the channel that scales linearly with the contour length of the
      polymer, in agreement with the scaling arguments developed by de Gennes for self
      avoiding confined polymers. This fundamental relationship allows us to measure
      directly the contour length of single DNA molecules confined in the channels, and
      the statistical analysis of the dynamics of the polymer in the nanochannel allows
      us to compute the SD of the mean of the extension. This statistical analysis
      allows us to measure the extension of lambda DNA multimers with a 130-nm SD in 1
      min.

PMID- 15252204
TI  - In defense of the cell: TRIM5alpha interception of mammalian retroviruses.

PMID- 15252206
TI  - Different elements of mini-helix 1 are required for human growth hormone or
      prolactin action via the prolactin receptor.
AB  - Human growth hormone (hGH) and prolactin (hPRL) have a low sequence homology, but
      both bind and activate hPRL receptors. hGH also binds hGH receptors. hGH has 22
      and 20 kDa forms; residues 32-46 have been deleted by alternative RNA splicing to
      create the smaller form. hGH requires F44 for activity through the hPRL receptor,
      but not for activity through the hGH receptor. The deletion of F44 from hGH has
      the same effect as removal of residues 32-46 (approximately 200-fold loss in
      activity), indicating the importance of F44 in hGH when activating the hPRL
      receptor. In contrast, when the homologous F50 is deleted from hPRL little or no
      activity is lost, indicating that this highly conserved phenylalanine is not
      required for the action of hPRL. Deletion of residues 41-52 (a non-conserved
      sequence homologous to residues 32-46 of hGH) reduced the activity of hPRL by >14
      000-fold. This region is essential for the biological activity of hPRL. As these
      two proteins have evolved from a common ancestor, they have retained the
      requirement for this region but need different structural elements to activate
      hPRL receptors. Such diversity represents an opportunity to fine-tune hormone
      activity.

PMID- 15252205
TI  - Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of
      parkin regulates its E3 ubiquitin ligase activity.
AB  - Many hereditary and sporadic neurodegenerative disorders are characterized by the
      accumulation of aberrant proteins. In sporadic Parkinson's disease, representing
      the most prevalent movement disorder, oxidative and nitrosative stress are
      believed to contribute to disease pathogenesis, but the exact molecular basis for
      protein aggregation remains unclear. In the case of autosomal recessive-juvenile
      Parkinsonism, mutation in the E3 ubiquitin ligase protein parkin is linked to
      death of dopaminergic neurons. Here we show both in vitro and in vivo that
      nitrosative stress leads to S-nitrosylation of wild-type parkin and, initially,
      to a dramatic increase followed by a decrease in the E3 ligase-ubiquitin
      proteasome degradative pathway. The initial increase in parkin's E3 ubiquitin
      ligase activity leads to autoubiquitination of parkin and subsequent inhibition
      of its activity, which would impair ubiquitination and clearance of parkin
      substrates. These findings may thus provide a molecular link between free radical
      toxicity and protein accumulation in sporadic Parkinson's disease.

PMID- 15252207
TI  - Toxicity-based selection of Escherichia coli mutants for functional recombinant
      protein production: application to an antibody fragment.
AB  - We propose a novel approach to the selection of Escherichia coli bacterial
      strains improved for the production of recombinant functional proteins. This
      approach is based on aggregation-induced toxicity of recombinant proteins. We
      show that selection of clones displaying a reduced toxicity is an efficient means
      of isolating bacteria producing recombinant protein with reduced aggregation in
      favour of correct folding. For an efficient selection, we found that time of
      toxicity induction must be precisely determined and recombinant protein must be
      expressed as a fusion with a protein whose activity is easily detectable on
      plates, thus allowing elimination of non-productive mutants. Choosing the
      expression to the periplasmic space of an scFv fragment fused to the N-terminus
      of alkaline phosphatase as a model, we selected chromosomal mutations that reduce
      aggregation-induced toxicity and showed that they concomitantly improve
      production of a functional recombinant hybrid. The effects of the mutations
      isolated could then be cumulated with those of other strategies used for
      recombinant scFv production. Thus, we could ensure a 6- to 16-fold increase in
      production of a functional scFv-PhoA hybrid. This is the first report
      demonstrating the possibility of directly selecting on agar plates E.coli strains
      improved for functional recombinant protein production from a large bacterial
      mutant library.

PMID- 15252208
TI  - Increase in peripheral benzodiazepine receptors on monocytes in fibromyalgia.
AB  - OBJECTIVE: The aim of this study is to evaluate the expression of Peripheral
      Benzodiazepine Receptors (PBRs) on leukocytes in patients affected by primary
      fibromyalgia and to argue their possible role in pain perception and in
      modulation of immunologic process. METHODS: The expression of PBRs has been
      evaluated by flow cytometry on monocytes, on lymphocytes and on granulocytes in
      twenty patients with primary fibromyalgia, with indirect immunofluorescence
      methods. RESULTS: Upregulation of leukocyte PBRs expression has been demonstrated
      in fibromyalgia. A statistically significant difference has been documented only
      in monocytes. The monocyte PBRs expression was 26.74 +/- 14.84 MIF in
      fibromyalgia versus 17.45 +/- 8.54 MIF in controls (P < 0.023). Upregulation of
      PBRs expression, although not statistically significant, was also observed in
      lymphocytes and granulocytes. CONCLUSIONS: The monocyte PBRs overincrease in
      fibromyalgia may be due to abnormalities in the regulation of pain or to
      inflammation. It might perhaps explicate the possible mechanisms of therapeutic
      response to benzodiazepine in fibromyalgia.

PMID- 15252209
TI  - A longitudinal study of joint pain in older people.
AB  - BACKGROUND: Joint pain is extremely common in older people, but its natural
      history has been little described in the UK literature. METHODS: A UK general
      practice population was followed for 1 yr in 1998. There were 4804 subjects aged
      75 yr and over who accepted the offer of health screening. Assessments by postal
      questionnaire using the Elderly At Risk Rating Scale, which includes one question
      specifically covering joint pain. RESULTS: Some degree of joint pain was reported
      by 83%. This was related to age and female gender. The presence of pain was
      strongly related to mobility, energy and sadness. Over 1 yr, 18% acquired or had
      increased frequency of pain, while 14% had reduced frequency of pain. Resolution
      was associated with preserved indoor mobility, and functional recovery. There was
      little relationship between joint pain and adverse outcomes. CONCLUSIONS: Joint
      pain is very common in older people, fluctuates in frequency over time, and is
      strongly linked to psychological factors as well as disability. A positive
      approach to active management of joint pain is justified, and will be rewarded by
      improved quality of life for older people.

PMID- 15252210
TI  - Fall-related risk factors and osteoporosis in women with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of
      osteoporotic fractures. Whilst numerous studies have demonstrated low bone
      density in RA, few studies have examined the risk of falling, which is another
      major contributor to the pathogenesis of fractures (particularly hip fractures).
      OBJECTIVES: The aim of this study was to see if fall risk is increased in women
      with RA, define high-risk subgroups, and determine what proportion of women have
      increased risk of hip fracture due to osteoporosis and due to increased fall
      risk. METHODS: We performed a case-control study of older women with RA (n = 103)
      compared with women without RA referred for open access bone densitometry (n =
      203). We measured bone density using dual-energy X-ray absorptiometry and fall
      risk factors (visual acuity, ability to perform standups, and heel-toe walking).
      RESULTS: More women with RA gave a history of a previous fall compared with
      controls (54 vs 44%), although this was just short of being statistically
      significant (difference 10%, 95% CI -2 to 22). Women with RA were more likely to
      have abnormal heel-toe walking and inability to perform standups compared with
      controls (P<0.001); however, visual acuity was similar between cases and
      controls. Femoral neck osteoporosis was found in 31% and increased fall risk in
      68% of women with RA. Women with RA who underperformed in heel-toe walking and
      were unable to do standups had significantly higher ESR, Health Assessment
      Questionnaire score and tender joint count. RA symptoms/signs localized to the
      knees and ankles were more likely to be associated with the presence of fall risk
      factors. CONCLUSIONS: Fall-related risk factors predictive of hip fracture are
      common in women with RA. Fall risk needs to be considered when RA patients are
      being treated for osteoporosis and further work needs to be done to help reduce
      the risk of falling and fracture in women with RA.

PMID- 15252211
TI  - Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered
      lymphocyte subpopulations and monocytes in Behcet's disease.
AB  - OBJECTIVE: In Behcet's disease (BD), several abnormalities of lymphocyte
      subpopulations have been described. Standard treatment comprises
      immunosuppressive drugs. We successfully treated 50 patients with ocular BD with
      interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is
      counterintuitive because IFN-alpha is immunostimulatory and can sometimes even
      induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid
      arthritis. The aim of the present study was to elucidate the immunomodulatory
      effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC)
      in BD by examining changes in the distribution of lymphocyte subpopulations under
      IFN-alpha2a treatment. METHODS: Fourteen patients with ocular BD were evaluated
      before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy
      controls. PBMC were stained with monoclonal antibodies and measured by flow
      cytometry. RESULTS: Compared with the controls there is a significant elevation
      of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells,
      natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells
      (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment
      with IFN-alpha2a. Numbers of naive T cells (CD8(+)/CD45(+)RA(+)/RO(-),
      CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells,
      CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly,
      whereas B cells increased. The previously reduced expression of HLA class I on
      monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51
      negative patients. CONCLUSION: These results implicate the participation of NK
      cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the
      pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts
      therapeutic effects. Alternatively, they may result indirectly from remission
      induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in
      HLA-B*51-positive patients might reflect an impaired expression of and antigen
      presentation by HLA-B*51.

PMID- 15252212
TI  - Antibody response to the human stress protein BiP in rheumatoid arthritis.
AB  - OBJECTIVES: The human stress protein BiP (immunoglobulin binding protein) has
      been implicated in the pathogenesis of rheumatoid arthritis (RA) since BiP was
      found to stimulate synovial T-cell proliferation and anti-BiP antibodies are
      present in the serum of RA patients. The aim of this study was the development of
      a rapid and reproducible enzyme-linked immunosorbent assay (ELISA) to determine
      the specificity and sensitivity of anti-BiP antibodies in RA. METHODS: An ELISA
      was developed that detected antibodies to BiP. The prevalence of anti-BiP
      antibodies was determined in sera from patients with early and established RA,
      sera antedating the onset of RA and sera from patients with other inflammatory
      and autoimmune diseases and healthy controls. RESULTS: We have confirmed the
      increased prevalence of antibodies to BiP in the sera of a large cohort of
      patients with established RA (specificity 71% and sensitivity 73%) and early RA
      (specificity 65% and sensitivity 66%). In pre-disease sera, median 2.5 yr
      (interquartile range 1.1-4.7) before symptoms of joint disease, the sensitivity
      for anti-BiP antibodies was 45% and the specificity was 65% for the development
      of RA. CONCLUSION: Antibodies to BiP are found in the sera of patients with RA
      and in sera antedating the onset of RA.

PMID- 15252213
TI  - Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical
      joints in juvenile idiopathic arthritis: a double-blind trial.
AB  - OBJECTIVE: Pharmacokinetic studies have shown that the biological effect of
      triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide
      (TH), if used at double the dosage. In this study we compared the efficacy of
      intra-articular TA at a dose twice that of TH in symmetrically involved joints,
      in children with juvenile idiopathic arthritis (JIA). METHOD: Children with
      active arthritis and a similar degree of inflammation in two symmetrical joints
      were enrolled in the study. The symmetry was assessed by both clinical
      examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg
      of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was
      blinded to the patient and to the physician. RESULTS: Thirty-seven patients, 30
      female, seven male, with JIA, entered the study. A total of 86 joints were
      injected. Twenty-one (53.8%) of the joints injected with TA relapsed first
      compared with only six (15.4%) of the joints injected with TH. In three (7.7%)
      relapse occurred simultaneously. Nine (23%) were still in remission after 24
      month follow-up. The percentage of joints with lasting remission was higher with
      TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months,
      respectively; log rank test P = 0.003). CONCLUSION: Even when TA is given at
      higher doses, TH is more effective and should be considered the drug of choice
      for intra-articular treatment of JIA.

PMID- 15252214
TI  - No association between tumour necrosis factor receptor type 2 gene polymorphism
      and rheumatoid arthritis severity: a comparison of the extremes of phenotypes.
AB  - OBJECTIVES: To assess the association between the tumour necrosis factor receptor
      2 (TNFR2) 196 M/R single-nucleotide polymorphism and rheumatoid arthritis (RA)
      severity by taking advantage of the extremes of phenotype that exist in
      arthritis. METHODS: From the Leiden Early Arthritis Cohort (1700 patients), we
      selected patients who initially had the diagnosis of definite or probable RA
      according to the ACR criteria and developed complete remission (71 patients) or
      had the worst progression, to destructive disease (72 patients). A group of 135
      healthy controls was included. The TNFR2 genotype was determined in these groups.
      RESULTS: The extremes of phenotypes did not differ significantly in genotype
      distribution. No difference in genotype distribution between rheumatoid arthritis
      patients and healthy controls was observed. CONCLUSION: Our study demonstrates
      that even by comparing the extremes of phenotypes no association between the
      TNFR2 genotype and disease severity can be detected in Caucasian patients with
      sporadic RA.

PMID- 15252215
TI  - The DAS28 in rheumatoid arthritis and fibromyalgia patients.
AB  - OBJECTIVE: To compare the DAS28 (Disease Activity Score including a 28-joint
      count) values of rheumatoid arthritis (RA) and fibromyalgia (FM) patients, and to
      establish whether high pain levels and impaired mood influence DAS28 values.
      METHODS: DAS28 values were calculated in 62 consecutive patients with RA and in
      26 patients suffering from FM. Values for DAS28 scores as well as for the single
      items of the patient cohorts were compared using Student's t-tests. To evaluate
      the item weighting and internal consistency of the total score factor analysis
      was performed and Cronbach's alpha calculated. RESULTS: RA patients showed a mean
      DAS28 score of 4.23 (+/-1.2; range 0.77-7.46) and in FM patients the mean DAS28
      came to 4.04 (+/-1.13; range 1.19-6.28). DAS28 values of RA and FM patients were
      not significantly different statistically. Comparing the single components of the
      score, however, highly significant differences (P<0.0005) occurred between RA and
      FM patients. Cronbach's alpha for the DAS28 in RA patients amounted to 0.7329,
      indicating high internal consistency, whereas in FM patients it was 0.4832.
      CONCLUSION: The DAS28, as expected, proved to be inappropriate to express disease
      activity in FM patients. DAS28 values for expressing disease activity in RA
      patients may be flawed by coexisting FM and should therefore be regarded with
      caution as high pain levels more than impaired mood may lead to higher total
      scores.

PMID- 15252217
TI  - Using signaling pathways to overcome immune tolerance to tumors.
AB  - The ability of tumors to evade the immune system is thought to result from the
      inability of T lymphocytes to recognize and respond to tumor antigens. This lack
      of T cell response may depend on a failure of dendritic cells to present antigen
      in the proper context so that T cells become tolerant to tumor antigens rather
      than primed to undergo an immune response. The inability of tumor-associated
      dendritic cells to effectively present antigen may in turn depend on inhibitory
      factors in the tumor milieu. Recent experiments suggest that the administration
      of toll-like receptor ligands stimulate dendritic cell activation and maturation
      and may thus help overcome T cell tolerance to tumor antigens. Whether or not
      such an approach is clinically feasible remains to be seen.

PMID- 15252218
TI  - E3 ligases in T cell anergy--turning immune responses into tolerance.
AB  - Peripheral tolerance is an important strategy used by the immune system to
      prevent self-reactive lymphocytes from attacking host tissues. A variety of
      mechanisms contribute to peripheral tolerance, among them activation-induced cell
      death, suppression by regulatory T cells, and T cell anergy or unresponsiveness.
      Recent work has led to a better understanding of the cell-intrinsic program that
      establishes T cell anergy. A major insight is that during the induction phase of
      anergy, incomplete stimulation (T cell receptor stimulation without
      costimulation) leads via calcium influx to an altered gene expression program
      that includes up-regulation of several E3 ubiquitin ligases. When the anergic T
      cells contact antigen-presenting cells, intracellular signaling proteins are
      monoubiquitinated and targeted for lysosomal degradation, thus decreasing
      intracellular signaling and also resulting in decreased stability of the T cell
      antigen-presenting cell contact. We propose a molecular program leading to T cell
      anergy and discuss other proteins that may play a role.

PMID- 15252219
TI  - Empowering targeted therapy: lessons from rituximab.
AB  - Rituximab, a monoclonal antibody directed against the B cell-specific protein
      CD20, has revolutionized lymphoma treatment by providing a highly effective form
      of therapy with relatively mild toxic side effects. Effective as a single agent
      against some forms of B cell lymphoma, rituximab also has a chemosensitizing
      effect, enhancing the efficacy of chemotherapy against other forms of the
      disease. Although the mechanisms whereby rituximab achieves its effects remain
      incompletely understood, these seem to involve at least three distinct phenomena:
      (i) antibody-dependent cell-mediated cytotoxicity, (ii) complement-mediated cell
      lysis, and (iii) stimulation of apoptosis in target cells. The latter occurs
      through interaction of complexes of rituximab and CD20 in lipid rafts, with
      elements of a signaling pathway involving Src kinases. Effector molecules trigger
      various gene expression events, leading to sensitization of malignant cells to
      proapoptotic stimuli. Lessons learned from the research on rituximab may be
      applied to the rational development of antibody-based therapies against other
      forms of cancer.

PMID- 15252223
TI  - [Economic efficiency of methadone maintenance and factors affecting it].
AB  - Methadone maintenance is effective in reducing injection drug use, needle
      sharing, and the overall mortality associated with opiate abuse. Scientific
      literature describes that efficiency of methadone maintenance program depends on
      many factors. Our analysis is based on description of economic research methods
      and on factors affecting economic efficiency of methadone maintenance. METHODS:
      Computerized Medline data base was searched by key words: "economic evaluation",
      "cost-effectiveness", "cost-utility", "methadone", "methadone dosage", "ancillary
      services", "treatment duration". Review and analysis. RESULTS: Methadone
      maintenance therapy has higher economic efficiency with 80-100 mg per day
      methadone dose. Doses lower than 40 mg per day are considered as inefficient.
      Some methadone programs limit treatment to 90 days or less, but such short
      treatment episodes are not likely to be cost-effective. Ancillary services are
      more cost-effective at the beginning of methadone maintenance program, than in
      the later stages of the program. Economic efficiency is higher when program
      involves more participants, than when more ancillary services are provided.
      CONCLUSIONS. Effectiveness of Methadone maintenance program affects methadone
      dosage policy, treatment duration and ancillary services.

PMID- 15252224
TI  - [Experimental analysis of therapeutic properties of Rhodiola rosea L. and its
      possible application in medicine].
AB  - The paper presents a review of the scientific publications on Rhodiola rosea L.
      known for its adaptogenic characteristics. Biologically active substances
      salidroside, rosin, rosavin, rosarin and tyrosol, which are mainly found in plant
      rhizomes, demonstrate therapeutic effect. These active components effect the
      central nervous system by increasing the ability to concentrate, the mental and
      physical power; they are efficient in the asthenic states and improve general
      resistance of the cells and the organism against the harmful outer influence.
      They also prevent the heart system from stress and arrhythmias, and posses some
      antioxidant activity. Some data confirm that the Rhodiola rosea L. preparations
      stop the growth of the malignant tumors and metastases in the liver. Some
      preclinical and clinical data of the golden root preparations are discussed in
      the survey. The interaction of the herb with other medicines, its usage and
      effect, recommended doses, and its side effects are also reviewed in the paper.

PMID- 15252225
TI  - The epidemiology and treatment of adult patients with hand burns in Kaunas
      University of Medicine Hospital in 1985, 1995, 2001 and 2002.
AB  - This study reviews the epidemiology of adult patients with hand burns admitted to
      Kaunas University of Medicine Hospital in Lithuania during selected four years
      (1985, 1995, 2001 and 2002). Two hundred and forty six cases were reviewed
      retrospectively with 74.4% of males and 25.6% of females among them. Median of
      age was 40 years (38 males, 45 females). Fire (71.9%) was the most common cause
      of injury; scalds (15.4%) were the second most common reason. The median of
      burned total body surface area was 12%. Analyzing the burns, 58.9% of them
      occurred in urban area (57.1% full-thickness burns), and 41.1% in rural (42.9%
      full-thickness burns). The study revealed that 17.1% (42) males and 3.7% (9)
      females were affected by alcohol at the time of injury. Early skin grafting was
      performed in 29.4% cases (mostly in 2001, 2002), delayed--70.6% (mostly in 1985,
      1995) of all skin grafting operations. Early grafting was found to give better
      results in the length of hospital stay. Overall, the median of hospital stay
      significantly decreased and was 24 days (35 days in 1985, 19 days in 2002).

PMID- 15252226
TI  - [When can normal stress myocardial perfusion scans be observed in patients with
      chest pain and known or suspected coronary artery disease?].
AB  - The aim of this study was to establish characteristic clinical data in patients
      with normal stress myocardial perfusion scans. MATERIAL AND METHODS: 99mMIBI
      scintigraphy was performed following a one-day protocol (stress-rest) in 806
      patients (out of them 451 men) with suspected or known coronary artery disease. A
      bicycle exercise test response was estimated as pathological, non-pathological,
      borderline and non-informative. Myocardial perfusion was scored according to the
      size and severity of defect. RESULTS: Myocardial perfusion was normal in 287
      (35.6%) patients. Univariate analysis showed, that normal stress myocardial
      perfusion scans more often were established in women than in men (p=0.00001, odds
      ratio 8.55), in patients with atypical anginal or non-anginal chest pain than
      with typical angina (p=0.0001, odds ratio 1.92), in patients without previous
      myocardial infarction (p=0.0001, odds ratio 3.28) and without myocardial
      revascularization (p=0.0001, odds ratio 3.28). The characteristic bicycle
      exercise test data for normal scans were non-pathological response vs
      pathological (p=0.00001, odds ratio 3.03) and reason of discontinuance - target
      heart rate achieved (85% of maximum) vs ischemic changes (p=0.0005, odds ratio
      2.37). CONCLUSIONS: Normal stress myocardial perfusion scans were more often
      present in women, in patients with atypical angina or non-anginal chest pain, in
      patients without myocardial infarction and without myocardial revascularization.
      Achieved target heart rate and non-pathological response to exercise test were
      commonly observed in patients with normal perfusion scans.

PMID- 15252227
TI  - [Pathobiological determinants of atherosclerosis in youths: data from a
      macromorphometric and histomorphometric investigation of the aorta and coronary
      arteries].
AB  - We present a review of data from epidemiological and morphological studies
      carried out in Kaunas of atherosclerosis in youths. Since 1985, Kaunas has been a
      Collaborating Center involved with the World Health Organization and
      International Society and Federation of Cardiology studying the pathobiological
      determinants of atherosclerosis in youth. During the pilot study (1985-1987), we
      estimated the prevalence and extent of atherosclerotic lesions in the aorta and
      coronary arteries correlated to various risk factors in Kaunas residents aged 5
      to 44 years. Within the framework of this international study, we compared
      histomorphometric characteristics of arteries collected from trauma victims aged
      5 to 34 years in Budapest (Hungary), Heidelberg (Germany), Kaunas (Lithuania),
      Yaounde (Cameroon), and Mexico City (Mexico). These data revealed that males from
      countries with a high mortality from ischemic heart disease (Hungary, Lithuania,
      Germany) tended to have thicker intima in the thoracic and abdominal aorta and
      left anterior descending coronary artery than did males from countries with low
      mortality from ischemic heart disease (Mexico, Cameroon). We detected an
      increased mean intimal thickness of the abdominal aorta in male smokers aged 25
      34 years. Males with hypertension aged 15-24 and 25-34 years had a thicker intima
      in the aorta and left anterior descending coronary artery than normotensive
      males. The morphological and epidemiological studies of atherosclerosis in youths
      carried out in Kaunas demonstrated that aortic and coronary atherosclerotic
      lesions appeared as early as childhood and advanced until the lesions become
      clinically apparent in adulthood. Histomorphometric findings support the
      postulate that increased intimal thickness can be considered a structural
      determinant of atherogenesis. These data draw attention to the means for the
      primary prevention of atherosclerosis in youth.

PMID- 15252228
TI  - [Myocardial pathology in sudden ischemic death: peculiarities of morphologic
      diagnosis].
AB  - OBJECTIVE: The aim of the investigation was to determine morphological criteria
      of acute myocardial injures in sudden ischemic death. MATERIAL AND METHODS:
      Morphological investigation of the whole myocardium and coronary arteries in 170
      victims of sudden out-of-hospital death due to ischemic heart disease was
      performed in the framework of the international WHO program "Myocardial
      Infarction Register in Population" and joint (at that time) USSR-USA project on
      sudden death. RESULTS: It was established, that out-of-hospital sudden death due
      to ischemic heart disease in all cases is related to irreversible myocardial
      injury: 92.9% - to acute myocardial infarction, and 7.1% - to micronecrosis. The
      following phases of morphological development of infarction were determined:
      early myocardial infarction--in 48.8, definite--in 21.8, and progressing--in
      22.3%. Since the signs of early infarction were also found in 34 cases of
      progressing myocardial infarction, it was reasonable to suppose that in 117
      (71.1%) patients the occurrence of sudden out-of-hospital death due to ischemic
      heart disease was somehow connected with the very early and early phases of acute
      myocardial infarction. CONCLUSIONS: Accurate identification of early myocardial
      infarction is available only by microscopic investigation of histotopograms of
      the whole myocardium considering the complex of signs of cardiomyocyte alteration
      as well as early inflammatory reaction. Acute pathology (erosion or rupture of
      atherosclerotic plaque and thrombosis) of "culprit" coronary artery indirectly
      indicates regional myocardial irreversible injury.

PMID- 15252229
TI  - [Interscalene brachial plexus block for shoulder surgery].
AB  - OBJECTIVE: This study evaluates the clinical efficacy of interscalene brachial
      plexus block (according to G. Meier) for shoulder surgery. PATIENTS AND METHODS:
      Seventy-three patients, scheduled for the elective shoulder surgery, were
      included in this study. All patients received an interscalene block before
      surgery and a standard analgesia protocol after it. Minimal stimulating current,
      block performance time, the onset of sensory and motor blocks, duration of
      surgery and surgery type were recorded. The quality of nerve block was also
      evaluated by a surgeon. The duration of postoperative analgesia resulting from
      residual local anesthetic effect was expressed as the time to first requirement
      for post-operative pain medication. Satisfaction scores with a visual analog
      scale, side effects, circulatory and respiratory parameters were assessed.
      RESULTS: The success rate was 97%. For the nerve location a minimal stimulating
      current of 0.1 mA had been achieved. The median onset time of both motor and
      sensory blockade was <4 min. A complete muscle paralysis was observed after 21
      (16-30) min. Duration of sensory blockade was 420 (240-840) min. The time from
      the block placement to the first request for pain medication was 8 (4-32) hours.
      Side effects were minor. Patient satisfaction was high. CONCLUSIONS: Single
      injection interscalene brachial plexus block is a reliable anesthetic and
      effective method of providing postoperative pain relief after shoulder surgery.

PMID- 15252230
TI  - Transport proteins in rats' renal corpuscle and tubules.
AB  - The localization of transepithelial transport proteins for glucose and water
      reabsorption in renal corpuscle and tubules epithelium was observed. MATERIAL AND
      METHODS: Immunohistochemistry of normal male Wistar rats' kidney has been
      performed. Facilitated diffusion glucose transporter GLUT4, Na(+)-dependent
      glucose co-transporter SGLT1, a cargo transporter TGN38, and water transporter
      aquaporin-2 (AQP2) were used. RESULTS: An intensive GLUT4 expression in renal
      proximal tubules and in convoluted segment of distal tubules has been observed.
      The intensive SGLT1 expression was marked in all renal tubules, and also in the
      glomerulus of the renal corpuscle. TGN38 was expressed mainly in the S1 of
      proximal tubules and a bit weaker in the distal tubules. The most intensive AQP2
      expression in the proximal tubules and in the thin part of Henle's loop has been
      detected. In some cases AQP2 expression in the collecting tubules has been
      observed. The same tubules nephroni are marked heterogeneously. The distribution
      of transepithelial transport proteins in different parts of nephroni is also
      greatly heterogeneous because of weak determination of urinary system.
      CONCLUSION: The comparable transport-proteins distribution with technique of
      fluorescence immunohistochemistry in rats' renal corpuscle and tubules was
      elucidated. Data suggest that expression of glucose and water transepithelial
      transporter proteins is heterogeneous in all parts of nephron, and, probably, is
      in accordance with recycling of transport proteins.

PMID- 15252231
TI  - [Compensatory reactions of immune system and action of Purple Coneflower
      (Echinacea purpurea (L.) Moench) preparations].
AB  - The objective of the study was to investigate the mechanisms of action of Purple
      Coneflower (Echinacea purpurea (L.) Moench) preparations on the immune system and
      to define which part of the plant is the most effective as an immunostimulator.
      MATERIAL AND METHODS: The extracts from overground parts and roots of Purple
      Coneflower were injected into rabbits at the dose of 1 ml/kg. The stimulation of
      T lymphocytes in vitro was tested by incubation of rabbit blood with the
      different concentrations of the Purple Coneflower preparation (10, 50, 100
      microg/ml) and assessed by the method of spontaneous rosettes. The number of
      lymphocytes, which bind to heterogenic erythrocytes, was counted. In order to
      determine the local effect, 30 ml of Purple Coneflower preparation (95 mg of dry
      material/1 ml) was used for the rinsing of mouth cavity in humans. The reaction
      of phagocytosis was assessed by using latex particles and calculating
      phagocytosis activity and phagocytosis index. RESULTS: Purple Coneflower extracts
      from roots were more effective phytoimmunostimulators than those from overground
      parts. They significantly increased in vivo the number of leucocytes and
      lymphocytes, especially T lymphocytes, in peripheral blood of rabbits as compared
      with the control group (p<0.001). The stimulation of T lymphocytes by Purple
      Coneflower preparation in vitro was the most pronounced at the concentration of
      50 microg/ml (20.8+/-1.01% of spontaneous rosettes, p<0.001 with control). An
      increase in concentration till 100 microg/ml was followed by non-specific
      inhibition (9.16+/-1.6% of spontaneous rosettes, p>0.05 with control). Purple
      Coneflower preparations activated phagocytosis of neutrophils in vitro and in
      vivo. After rinsing mouth cavity with 30 ml of Purple Coneflower root preparation
      for 15 minutes, phagocytosis activity was significantly increased till 36%
      (p<0.05 as compared with the control (27%), where physiological solution was used
      for the rinsing). This local application of Purple Coneflower root preparation
      has significantly increased phagocytosis index up to 1.03 (p<0.02 as compared
      with the control index (0.65) after rinsing of the mouth cavity with
      physiological solution). CONCLUSIONS: Purple Coneflower preparations from roots
      activate the cellular immunity and stimulate phagocytosis of neutrophils in
      vitro, in vivo and after rinsing of mouth cavity.

PMID- 15252232
TI  - Psychological adjustment of children with congenital hypothyroidism and
      phenylketonuria as related to parental psychological adjustment.
AB  - Phenylketonuria and congenital hypothyroidism are the inherited metabolic
      diseases that can be diagnosed and successfully treated early from birth.
      Nevertheless, children with phenylketonuria and congenital hypothyroidism are
      found to be in the risk for psychological maladjustment. Parental adjustment - as
      significant condition for child's psychological adjustment--and related factors
      are explored in this study. Parents of 63 children with congenital hypothyroidism
      and phenylketonuria (age 2 to 14 years) answered the Child Behavior Checklist,
      Coping Strategies Questionnaire and the questionnaire on reactions to child's
      disease, relations with a sick child, with the spouse and other people. Severity
      of the disease and child's age are considered as well. Results of the study show
      that parental emotional (maladaptive) coping and indulgence of a sick child
      account for the higher rates of internalizing problems of children with
      phenylketonuria and congenital hypothyroidism. In addition, the higher rates of
      children's psychological problems are related to parental feelings of guilt as a
      reaction to child's disease.

PMID- 15252233
TI  - [Association of age-related maculopathy with ischemic heart disease and its risk
      factors in middle-aged population of Kaunas city].
AB  - AIM: To determine the prevalence of age-related maculopathy in a sample of
      Lithuanian middle-aged population and to assess the relationship between age
      related maculopathy and ischemic heart disease and its risk factors, including
      smoking, arterial hypertension, obesity, hyperglycemia, and dyslipidemias.
      MATERIAL AND METHODS: A random sample of urban population of 1357 adults (ranging
      from 35-64 years of age; 597 males and 760 females) living in Kaunas, Lithuania
      was examined during the interval from 2001 to 2002. Each participant underwent a
      comprehensive examination that included an ophthalmic examination. The presence
      of age-related maculopathy was determined by grading from fundus examination by
      indirect ophthalmoscopy, slit lamp examination, and color fundus photographs. The
      history, physical examination findings, and fasting blood samples provided data
      on possible risk factors. Age-adjusted logistic regression analysis was performed
      to determine the risk factors for age-related maculopathy. RESULTS: Early age
      related maculopathy was detected for 44 males and 40 females. The prevalence of
      age-related maculopathy increased steadily with age without significant
      difference between males and females. Multiple logistic regression analysis
      showed that increased diastolic blood pressure, obesity, hyperglycemia, ischemic
      ECG-abnormalities and history of myocardial infarction were significantly
      associated with age-related maculopathy in males aged 40-64 years. Current
      smoking and hyperglycemia were significantly associated with age-related
      maculopathy in females aged 40-64 years. CONCLUSIONS: Our study suggests that
      arterial hypertension, obesity, hyperglycemia, current smoking and positive
      history of cardiovascular disease are relevant risk factors for age-related
      maculopathy in middle-aged urban population.

PMID- 15252234
TI  - [Working conditions and workers' health impairments in drug distribution
      companies].
AB  - The aim of the study was to evaluate working conditions according to hygiene
      norms and to determine health impairments of drug distribution companies'
      workers. MATERIAL AND METHODS: Study was performed in summer of 2003 in drug
      distribution companies implementing good distribution practice. Study included
      588 workers. Health impairments for technical personnel and pharmacists were
      revealed using a questionnaire. RESULTS: Microclimatic work conditions:
      temperature, humidity, air movement during summer season at 11% workplaces did
      not correspond to hygiene norms. The main health impairments for pharmacists were
      various ophthalmological disorders. For technical personnel main health
      impairments were musculoskeletal disorders, as back pain and varicosis. They are
      related with repetitive spinal column movements, incorrect weight lifting, long
      fixed working position, etc. Based on criteria used for evaluation of workload,
      workers of drug distribution companies are attributable to strained work
      category.

PMID- 15252235
TI  - [Results of morphologic epidemiologic study of coronary arteries in Kaunas
      population aged 20-69 years: atherosclerotic lesions and their
      interrelationship].
AB  - OBJECTIVE: The object of study was the type, frequency and extent, as well as
      correlation of atherosclerotic lesions in Kaunas population aged 20-69 years.
      RESULTS: The frequency and intimal area of raised atherosclerotic lesions
      (fibrous and complicated plaque and calcinosis) are age-dependent. The increase
      of raised lesions area seems to alter at different decades of life. In men the
      most substantial progression in left anterior descending artery was observed at
      the fourth-fifth, in right coronary artery--at the fifth, and in both arteries of
      women - at the sixth decade of life. The area of fatty streaks is not dependent
      on age and comprises approximately 4-5% of intimal surface. We observed weak
      negative correlation between area of raised lesions and fatty streaks, and strong
      correlation between the area of all type of raised lesions in all three coronary
      arteries. CONCLUSIONS: The coronary artery atherosclerosis is progressing with
      age. Age decades, when increase of raised lesion area is observed, correspond to
      age periods, in which mortality due to ischemic heart disease increases
      significantly.

PMID- 15252236
TI  - [Reliability of data of death causes: comparison of premortem and verified by
      autopsy postmortem diagnoses].
AB  - OBJECTIVE: The goal of the investigation was to evaluate the accuracy of medical
      diagnostics of death causes. MATERIAL AND METHODS: In the framework of population
      based postmortem examination program the latest premortem and postmortem
      diagnoses of the underlying (principal disease), direct (lethal complication) and
      contributory (contributory pathology) causes of death of 1030 deceased and
      autopsied people of local randomized unit (Jonava district) autopsy study were
      compared. RESULTS: The discrepancy between premortem and postmortem diagnoses was
      35.3% in the category "circulatory system diseases", 26.5% in the category
      "malignant neoplasms", 41.1% in the category "lethal complications", and more
      than 50% in the category "contributory pathology". CONCLUSIONS: The accuracy of
      data on underlying death cause is significantly limited due to overstating of
      circulatory system diseases, especially ischemic heart disease and understating
      of malignancies. Among mismatches in lethal complication cases more significant
      for outcome of disease were pneumonia and embolism of lung arteries, in
      contributory pathology--chronic bronchitis and ischemic heart disease.

PMID- 15252237
TI  - [Procalcitonin as a marker of the systemic inflammatory response to infection].
AB  - Despite advances in the diagnosis and treatment of infections diseases, sepsis
      and ensuing multiorgan failure are the major causes of morbidity and mortality in
      the intensive care units. Such manifestations of systemic inflammation as fever,
      leukocytosis, tachycardia, etc. may be noninfectious in origin and are neither
      specific nor sensitive for sepsis. Procalcitonin is a new potential marker for
      detection of bacterial, fungal and protozoal infections. Procalcitonin, a
      propeptide of calcitonin, is normally produced in the C-cells of the thyroid
      gland. Procalcitonin is a polypeptide consisting of 116 amino acids and with a
      molecular weight of about 13 kDa. During severe systemic infections it is
      produced by extrathyroidal tissues. Procalcitonin can be put to immediate use in
      both diagnostic and therapeutic decision-making. This review article discusses
      biology of procalcitonin, its laboratory determination, usage as an indicator for
      severe infection and sepsis, and comparison with circulating cytokines in severe
      infection. It also reviews value of procalcitonin in differentiation of
      infectious vs non-infectious inflammatory host response, possible elevation of
      procalcitonin in the absence of infection, its use for differentiation of viral
      and non-viral infections and as marker for prognosis and evaluation of therapy.
      Specific indications for determination of procalcitonin are also discussed.

PMID- 15252238
TI  - Construction of novel Brassica napus genotypes through chromosomal substitution
      and elimination using interploid species hybridization.
AB  - A synthetic Brassica napus rapeseed with genome composition of A(r)A(r)C(c)C(c),
      made by combining A(r) from B. rapa (A(r)A(r)) and C(c) from B. carinata
      (B(c)B(c)C(c)C(c)), is valuable for making new genes available to breeders and
      gaining heterosis in crosses. An intergenomic hybrid A(n)A(r)C(n)C(c) was made
      from a hybrid between natural Brassica napus (A(n)A(n)C(n)C(n)) and a synthetic
      rapeseed. To construct the synthetic Brassica napus, hexaploid plants (2n=54,
      A(r)A(r)B(c)B(c)C(c)C(c)) were first obtained through chromosome doubling of
      trigenomic hybrids (2n=27, A(r)B(c)C(c)) between Brassica carinata (2n=34) and B.
      rapa (2n=20). Pentaploid hybrids (2n=46, A(r)A(n)B(c)C(c)C(n)) were then produced
      by crossing the hexaploid with the pollen of natural B. napus (2n=38).
      Chromosomes with dual and single B(c) genomes were observed in somatic cells of
      hexaploid and pentaploid plants. About 80% of pollen mother cells of pentaploid
      hybrids had 19 or more bivalents, indicating that the bivalents from A(r)/A(n)
      and C(c)/C(n) chromosomes were normally formed. The occurrence of trivalents and
      quadrivalents at diakinesis suggested that B(c), A(n) and A(r) or B(c), C(n) and
      C(c) homologous pairing and exchange might happen. The variable number of
      laggards, 3 and 4 in most cases, were observed in the majority of PMCs at
      anaphase. Results from genomic in situ hybridization showed that the laggards
      belonged mainly to the B(c) genome, suggesting that the B(c) genome could be
      eliminated in the gametes of pentaploid hybrids. 16.15% of seeds derived from
      self-pollinated pentaploids have 38 chromosomes, and 90% of 38-chromosome seeds
      were completely excluded B(c) genome. The cytological results of this experiment
      suggested that it is possible to obtain new materials with genome composition of
      A(r)A(r)C(c)C(c) for rapeseed breeding.

PMID- 15252239
TI  - Behaviour of nucleolus organizing regions (NORs) and nucleoli during mitotic and
      meiotic divisions in budding yeast.
AB  - Spatial organization and segregation behaviour in mitosis and meiosis of nucleoli
      and NORs of Saccharomyces cerevisiae were examined by fluorescence in situ
      hybridization (FISH) and immunostaining, and integrated with previous
      ultrastructural studies. Our observations suggest that in interphase the NOR
      bearing chromosome arm forms a hairpin-shaped loop inside the nucleolus, unlike
      the other arms which adopt a Rabl-like orientation. Prior to mitosis and meiosis,
      the appearance of the NOR changes from puffed to thread-shaped. In mitosis, it is
      stretched between the mother and daughter nuclei and seems to be among the last
      regions where chromatids separate. The nucleoli remain intact and split at the
      end of anaphase. Similarly, during meiosis I, intact nucleoli trail behind the
      separating homologous NORs and are partitioned equally to the two half-nuclei.
      During the second meiotic division, however, the nucleolus, together with a major
      portion of the nucleoplasm and the nuclear pore complexes, are not included in
      the spores. The behaviour of nucleoli in meiotic mutants and a strain with
      extrachromosomal rDNA suggests that they are not actively extruded but rather are
      lost due to their detachment from the separating chromosomes. We discuss the
      possibility that the exclusion of the nucleolus from the spores serves the
      disposal of agents that resort to the nucleolus, and has a role in spore dormancy
      or rejuvenation.

PMID- 15252240
TI  - Nascent RNA synthesis in the context of chromatin architecture.
AB  - Based on the idea that chromatin domains provide physical barriers for large
      molecules and multi-enzyme complexes, including the components of the
      transcription machinery, it has been proposed that transcription should be
      confined to the surfaces of chromatin domains. As a consequence nascent RNA
      should accumulate in the interchromatin space, which is thought to provide a
      special nuclear compartment involved in transcription, as well as in the
      processing and export of RNA (Cremer et al. 1993, Cremer & Cremer 2001). To
      further address the relationships between chromatin organization and RNA
      synthesis, we investigated the localization of BrUTP-labelled nascent RNA in HeLa
      cells stably expressing green fluorescent protein (GFP)-tagged histone H2B, which
      highlights the chromatin structure. Our results showed that nascent RNA does not
      preferentially localize within the interchromatin space. The findings do not
      support the idea that the interchromatin space provides a nuclear compartment
      playing an essential role in nascent RNA synthesis. However, the results are in
      agreement with the emerging view that even condensed chromatin domains display a
      highly dynamic organization and are not a physical barrier for transcription
      factors.

PMID- 15252241
TI  - Phylogenetic history of the Sifakas ( Propithecus: Lemuriformes) derived from
      cytogenetic studies.
AB  - The R-banded karyotypes of the different subspecies of Propithecus diadema and P.
      verreauxi are compared to each other and to that of P. tattersalli, as well as
      those previously reported of Indri indri and Avahi laniger. This comparison shows
      that the different subspecies of P. verreauxi possess the same karyotype and
      that, among P. diadema, P. d. diadema and P. d. perrieri share the same karyotype
      differing from that of P. d. edwardsi by one Robertsonian translocation. The
      karyotype of P. tattersalli differs at least through 17 and 9 rearrangements from
      those of P. diadema and P. verreauxi, respectively. This provides strong
      arguments in favor of its specific status. The phylogenetic diagram proposed
      confirms the early separation of Avahi and the relatively late divergence of the
      four other species. A populational evolution has occurred between these four
      species, P. tattersalli and P. verreauxi sharing the largest number of
      rearrangements (six), while the numbers of rearrangements shared by the other
      species are two for Indri and P. verreauxi, three for P. tattersalli and Indri,
      and three for P. tattersalli and P. diadema. No branch is common to two species
      of Propithecus.

PMID- 15252242
TI  - Conserved patterns of gene expression in mice and goats in the vicinity of the
      Polled Intersex Syndrome (PIS) locus.
AB  - The PIS mutation is a genomic ~12-kb deletion affecting long-range gene
      transcription and causing XX sex reversal and hornlessness in goats by
      simultaneous long-range action on two genes, gPISRT1 and gFOXL2. In this study, a
      comparative human/mouse analysis of the orthologous region was carriedout,
      permittingthe targeting of genes in the 1-Mb environment, and identification of
      previously unknown mouse orthologues for Pisrt1, Bpesc1 and Chr3syt, and a human
      orthologue for PISRT1. PCR primers were defined and made it possible to analyse
      tissue-specific gene expression in mice and goats for 10 and 8 genes,
      respectively. The profile of expression was analysed by principal component
      analysis (PCA). The results indicate that FAIM (Fas apoptotic inhibitory
      molecule) is expressed similarly to FOXL2 (the primary determinant of ovary
      development located 280 kb away from the PIS mutation). However, we could
      demonstrate in goats that the PIS mutation has no direct effect on FAIM
      expression. Therefore, FAIM could contribute to normal ovarian function by
      inhibiting the apoptotic effect of Fas in the ovary but it relies on other
      regulatory elements.

PMID- 15252243
TI  - Visualization of the S-locus region in Ipomoea trifida: toward positional cloning
      of self-incompatibility genes.
AB  - Self-incompatibility (SI) in Ipomoea trifida is regulated by a single S locus
      with multiple alleles. Identification of SI genes in the S -locus region by
      positional cloning is one of the most important goals for understanding sexual
      reproduction in this species. Despite our intensive efforts to construct
      bacterial artificial chromosome (BAC) contigs covering the S -locus region, a gap
      was observed in the core region of the potential S locus. In order to confirm the
      physical linkage of two non-overlapping BAC contigs in the S -locus region and to
      determine the size of the gap between them, fluorescence in-situ hybridization
      (FISH) was performed on mitotic chromosomes and extended DNA fibres using
      previously isolated S -linked BAC clones as probes. The information obtained from
      this work would be useful for molecular cloning of the SI genes by a chromosome
      walking approach. In addition, we showed that strong suppression of recombination
      in the S locus was not related to the centromere because the S locus was mapped
      to one end of a chromosome.

PMID- 15252244
TI  - Cloning, characterization and localization of Chinese hamster HP1 isoforms.
AB  - The Chinese hamster is one of the few mammalian species that are characterized by
      relatively poor heterochromatin content. It was intriguing to test whether or not
      the lack of large blocks of heterochromatin in the hamster chromosomes could be
      correlated with the absence or species-specific differences of the HP1 proteins,
      the main structural components of heterochromatin. To address this, we attempted
      to clone HP1 from the Chinese hamster. It is shown here that all three isoforms
      of HP1 known in mammals are present in hamster, and the amino acid sequences
      deduced from the cDNAs of the isoforms are 97-100% identical to those of the
      known mammalian homologues. All three isoforms are localized mainly in
      heterochromatic regions in the native chromosomes and nuclei. The hamster HP1
      alpha gene was cloned, sequenced and mapped to the short arm of hamster
      chromosome 2. These data indicate that the Chinese hamster has all the HP1
      components necessary for the establishment of heterochromatin. The limited amount
      of heterochromatin in hamster cells may probably be attributed to the unusual
      satellite DNA content of the hamster genome.

PMID- 15252245
TI  - Multidirectional chromosome painting between the Hirola antelope (Damaliscus
      hunteri, Alcelaphini, Bovidae), sheep and human.
AB  - Chromosome specific painting probes of human, sheep and the Hirola antelope (
      Damaliscus hunteri ) derived by flow sorting of chromosomes were used in multi
      directional chromosome painting experiments to better define the karyological
      relationship within Bovidae species (specifically, Caprini and Alcelaphini
      tribes) and humans. Although not all chromosomes of Damaliscus hunteri could be
      resolved into single peaks by flow-sorting we managed to present a complete
      homology map for chromosomes between the three species. When comparing the
      karyotype of Damaliscus hunteri with human all of the main known motives in
      mammalian chromosome evolution are present (i.e. associations of human homologous
      chromosomes 3-21, 4-8, 7-16, 14-15, 16-19 and two forms of 12-22) which were also
      confirmed with the sheep paint probes. Further, we observed those patterns that
      have been described as common derived traits for artiodactyls (i.e. associations
      of human homologous chromosomes 5/19 and a complex alternating pattern of
      hybridizations with human chromosome 14 and 15 probes). As known from classical
      karyotyping some of the Damaliscus chromosomes are biarmed and were supposedly
      involved in Robertsonian translocations frequently found in karyotype evolution
      of bovids. We refined these rearrangements with the molecular probes and also
      delineated a chromosome painting pattern that should be the result of a
      paracentric inversion in the Damaliscus hunteri karyotype. This study
      demonstrates that multidirectional chromosome painting will be a valuable tool
      for the investigation of the dynamics of chromosome evolution in exotic bovid
      species.

PMID- 15252246
TI  - Auricular reconstruction: an update.
AB  - PURPOSE OF REVIEW: One of the greatest challenges in facial plastic surgery is
      total auricular reconstruction. The ability to construct a fully satisfactory
      complete external ear has for centuries been an elusive goal. With advancing
      standards and expectations in plastic surgery, greater focus is being directed to
      this arena of reconstruction as well. RECENT FINDINGS: With advances both in
      surgical technique and biotechnology, an expanding range of options is available
      to the reconstructive surgeon who is willing to take on this still formidable
      task. While progress continues to be made in the detailing of costal cartilage
      grafts and soft-tissue rearrangement, it is also being made with the use of
      alloplastic implants and prostheses. The most promising field of advances, with
      the hope of eventual clinical utility, lies in the realm of bioengineering with
      cultured cartilage. SUMMARY: Review of the literature over the past year reveals
      several reports describing advances made in the development of cultured
      chondrocytes with attempts to direct special shape to the manufactured
      neocartilage. Though advances continue to be made, actual clinical applicability
      of this technology is still insufficient while expectation continues that this
      will eventually become integral to total auricular reconstruction.

PMID- 15252247
TI  - Current concepts in lip reconstruction.
AB  - PURPOSE OF REVIEW: Approximately 25% of all oral cavity carcinomas involve the
      lips, and the primary management of these lesions is complete surgical resection.
      The management of the resulting lip defect remains a significant reconstructive
      challenge, requiring meticulous preoperative planning and surgical technique to
      optimize the functional and cosmetic outcome. Reviewed here are the accepted
      techniques of lip reconstruction, as well newer techniques that have been
      reported. RECENT FINDINGS: There have been no major advances in lip
      reconstruction; rather, continued improvement on accepted techniques. The main
      goals of reconstruction remain the restoration of oral competence, maintenance of
      oral opening, and the restoration of normal anatomic relations such that both the
      active (smile) and passive (form) cosmetic outcome is acceptable. The
      reconstruction should be tailored to the individual needs of the patient and
      should take into account the patient's condition, local tissue characteristics,
      previous treatment(s), and functional needs (eg, denture use), in addition to the
      size and location of the defect. SUMMARY: The lips play a key role in facial
      expression, speech, and eating. This requires meticulous attention to
      preoperative planning and surgical technique to maximize the functional and
      cosmetic outcome. It is important to assess local tissue characteristics (skin
      laxity) and previous treatment (surgery and/or irradiation) before the surgical
      plan is made final. Local tissue should be used whenever possible to provide the
      least donor site morbidity and the best overall tissue color and texture match.
      Whenever possible, dynamic reconstruction should be attempted. Careful
      preoperative assessment and planning will allow the surgeon to reach an
      acceptable balance between form and function with the reconstruction.

PMID- 15252248
TI  - Mandibular reconstruction in 2004: an analysis of different techniques.
AB  - PURPOSE OF REVIEW: The field of mandibular reconstruction has evolved
      dramatically over the past fifty years. Numerous advances in microsurgical
      technique, plating technology and instrumentation, and an understanding of donor
      site angiosomes have made consistent and reliable mandibular reconstruction
      possible. Refinements in technique continue to improve the functional and
      aesthetic outcomes of oromandibular reconstruction. This review discusses the
      current state-of-the-art techniques for mandibular reconstruction and highlights
      the latest innovations in technique. RECENT FINDINGS: The most common indication
      for oromandibular reconstruction remains ablative surgery for advanced neoplastic
      processes of the oral cavity and oropharynx. Reconstruction of these complex
      three-dimensional composite bony and soft-tissue defects is paramount for
      rehabilitation of form and function. Vascularized osseous free tissue transfer is
      the state-of-the-art for mandibular reconstruction. The long-term excellent
      functional and aesthetic outcomes of this technique have recently been reported.
      The most commonly used free flaps for mandibular reconstruction are the fibula,
      iliac crest, and scapula. Each of these typically accepts endosseous implants
      improving functional outcomes. The use of mandibular reconstruction plates and
      coverage with a soft-tissue flap remains a reconstructive option for selected
      patients. The latest refinements in technique include temporary intraoperative
      external fixation, the use of periosteal free flaps, distraction osteogenesis,
      and development of biodegradable biopolymer scaffolds for mandibular defects.
      SUMMARY: Oromandibular reconstruction, although a challenge for the head and neck
      reconstructive surgeon, is now reliable and highly successful with excellent long
      term functional and aesthetic outcomes.

PMID- 15252249
TI  - Contemporary skull base reconstruction.
AB  - PURPOSE OF REVIEW: Tumors of the skull base that would have been considered
      inoperable thirty or forty years ago are now routinely resected with reliable
      results due to the advancement of modern reconstructive techniques. High
      mortality rates were common prior to the use of vascularized tissue for skull
      base repair. However, the advent of local flap reconstruction for skull base
      defects in the 1960s revolutionized skull base surgery. The use of regional flaps
      in the 1970s and 1980s allowed skull base surgeons to perform more extensive
      surgeries, but complication rates were still quite high. RECENT FINDINGS:
      Experience with free tissue reconstruction increased through the 1980s and 1990s
      and has become a reliable method to separate the intracranial from extracranial
      environments. Free tissue transfer has allowed surgeons to address the large
      volume defects created by extensive skull base resections and has provided
      dependable, vascularized tissue that is relatively resistant to adjuvant
      radiation. Local flaps have also become a powerful reconstructive tool in
      conjunction with free tissue transfer, and in some select cases, may be
      sufficient alone for reconstruction. SUMMARY: The prevention of serious
      complications after skull surgery has improved with the use of vascularized
      tissue. Depending on the anatomic site, the extent of the defect, and the quality
      of local tissues, either free tissue transfer and/or local flap reconstruction is
      preferred. Regional flap reconstruction should be reserved for cases where
      alternative reconstructive techniques are not available.

PMID- 15252250
TI  - Use of the anterolateral thigh flap for reconstruction of the head and neck.
AB  - PURPOSE OF REVIEW: The anterolateral thigh free flap has achieved recent
      popularity in North America for the reconstruction of head and neck defects after
      ablative surgery. The flap is most often based on either the septocutaneous or
      musculocutaneous perforators of the descending branch of the lateral circumflex
      femoral artery. Its versatility allows for a subcutaneous, fasciocutaneous,
      myocutaneous, or adipofascial flap to be obtained. RECENT FINDINGS: Recent
      publications have described the utility of the anterolateral thigh flap for
      reconstruction of head and neck defects. It has been used successfully in the
      reconstruction of the laryngopharynx, oral cavity, oropharynx, external skin, and
      maxilla. Furthermore, when a thinner flap is needed, a suprafascial anterolateral
      thigh flap may be raised or the flap may be thinned after it is obtained.
      SUMMARY: The anterolateral thigh flap is a highly versatile and reliable flap for
      use in the reconstruction of various soft tissue defects of the head and neck.
      This flap has gained great popularity in mainland China, Taiwan, and Japan given
      its versatility, ability for a two-team approach, and minimal donor site
      morbidity. However, it has not met the same enthusiasm in Europe and North
      America because of the relative difficulty in perforator dissection, reported
      variations of the vascular anatomy, and the presumed increased thickness of the
      anterolateral thigh tissue in the Western population in comparison with the
      patient population of the Far East. These obstacles may be overcome by increased
      surgical experience and by the ability to create a thinner suprafascial flap or
      thinning the flap after it has been obtained.

PMID- 15252251
TI  - Functional outcomes after free flap reconstruction of the upper aerodigestive
      tract.
AB  - PURPOSE OF REVIEW: When the complex structures of the upper aerodigestive tract
      are disrupted after resection of head and neck tumors, an appropriate
      reconstructive option should be chosen in an attempt to regain maximum function.
      Reconstructions using microvascular free tissue transfer offer unparalleled
      flexibility, both in tissue composition and in placement. This article will
      examine functional outcomes after free flap reconstruction of the upper
      aerodigestive tract. RECENT FINDINGS: With the maturation of free tissue transfer
      techniques, functional outcomes are being analyzed with increasing frequency.
      Recent reports show promising results for free flap reconstruction of oral
      cavity, oropharyngeal, and hypopharyngeal soft tissue defects, as well as for
      bony mandibular and maxillary defects. SUMMARY: For both soft tissue and bony
      defects of the upper aerodigestive tract, microvascular free flaps provide good
      functional outcomes. In the future, randomized studies are needed to compare the
      functional outcomes of microvascular free flaps with those of other
      reconstructive options.

PMID- 15252252
TI  - Tissue engineering: the current status of this futuristic modality in head neck
      reconstruction.
AB  - PURPOSE OF REVIEW: To define tissue engineering and describe the components that
      are involved in engineering tissue. To provide examples of the most recent
      developments in tissue engineering as they apply to the otolaryngologist. To
      provide a general overview of selected exciting advances outside the field of
      general otolaryngology but of general interest to the reconstructive community.
      RECENT FINDINGS: Tissue engineering is a rapidly evolving field that can be
      defined as the regeneration of new tissues through the use of biologic mediators
      and matricis. The three components required are scaffolds, signaling molecules,
      and cells. A significant amount of work has been done to generate bone,
      cartilage, cornea, and vascular grafts. Tissue engineered bone is the only tissue
      type that has been evaluated in Phase III clinical trials and is in routine
      clinical use. Engineered bone from BMP-2 and BMP-7 is used in orthopedics for
      lumbar fusions and long bone nonunions. Clinical application of bone tissue
      engineering in the head and neck is limited to case reports. There has been
      success in tissue engineering with cartilage for the nose and ear in immune
      incompetent animal models but there has been difficulty with generating scaffolds
      that do not incite an immune reaction in an immune competent model. The most
      advanced organ engineered is a bladder that has been successful in a canine
      model. SUMMARY: Tissue engineering holds the promise of "off the shelf" parts for
      reconstruction of tissues and organs. The widest clinical application is with
      bone in orthopedics. Applications in the head and neck are limited, at present,
      due to the immunogenicity of the scaffolds and the challenging wounds encountered
      in both cancer and cosmetic patients.

PMID- 15252254
TI  - Update on botulinum toxin use in facial plastic and head and neck surgery.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss current trends in the
      medicinal use of botulinum toxin in head and neck and facial plastic surgery. The
      basic science of botulinum toxin is presented along with a comparison of the
      subtypes currently available on the market. Site-specific applications of
      botulinum toxin in the head and neck region are presented. RECENT FINDINGS: The
      use of botulinum toxin continues to expand, both in volume and in number of
      applications. The main application of botulinum toxin in facial plastic surgery
      is in the effacement of dynamic or hyperkinetic facial lines. The granting of US
      Food and Drug Administration approval for the use of Botulinum Toxin type A in
      the treatment of glabella lines marks a major milestone for the more widespread
      usage of this product in cosmetic settings. Additional cosmetic applications
      include crow's feet, marionette lines, and platysma banding. Noncosmetic
      applications in the head and neck include dystonias (including torticollis),
      facial and generalized muscle spasms, migraine headaches, hyperhidrosis,
      spasmodic dysphonia, sialorrhea, gustatory sweating, and involuntary movement
      disorders. SUMMARY: The use of botulinum toxin in the treatment of hyperkinetic
      conditions and disorders of excessive salivation is well established and enjoys
      an excellent safety profile. The cosmetic use of botulinum toxin continues to
      expand. The chronic use of botulinum toxin specifically for cosmetic purposes is
      worthy of additional study.

PMID- 15252255
TI  - Update on lasers in facial plastic surgery.
AB  - PURPOSE OF REVIEW: Since the theory of selective photothermolysis was described,
      the field of facial plastic surgery has advanced the science behind laser: tissue
      interactions. Particular advances in skin cooling, hair removal, intense pulsed
      light, and uses for aesthetic and nonaesthetic skin problems are described in
      this review. RECENT FINDINGS: Continued basic science research in lasers has led
      to improvements in current technology available to the facial plastic surgeon.
      Advances in skin cooling have allowed for wider use in all Fitzpatrick skin types
      without concomitant adverse reaction. SUMMARY: Our understanding of laser science
      continues to expand our knowledge in basic laser: tissue interaction. An
      improvement in various laser mediums and adjunctive devices provides the facial
      plastic surgeon with instruments to treat a wider patient population. The benefit
      is a successful clinical and aesthetic result with improved safety.

PMID- 15252256
TI  - Update in three-dimensional imaging in facial plastic surgery.
AB  - PURPOSE OF REVIEW: Facial plastic surgeons have always relied on photography for
      preoperative and postoperative analysis, medicolegal documentation, and
      communication. The current standards for analysis and documentation of facial
      structures have been determined by obtaining measurements and parameters from two
      dimensional photographs or radiographs. However, the face and neck are three
      dimensional structures and require manipulation in three planes within the
      constraints of esthetics, stability, and function. Recent advances in technology
      have made three-dimensional imaging and analysis possible. RECENT FINDINGS: The
      ability to capture images in three dimensions has opened up new avenues for
      observation and has increased the ability to analyze changes after surgery.
      Whereas only linear distances, angles, and areas can be determined by use of two
      dimensional images, soft tissue volumetric data and surface topography can also
      be measured accurately; this can be helpful in validating changes in patients
      undergoing aging facial or orthognathic procedures. Recent studies have focused
      on descriptions of imaging techniques, validation of measurements, and the
      creation of normative data and its applications in surgery. SUMMARY: The
      availability of three-dimensional imaging and software systems presents new
      opportunities for the facial cosmetic surgeon to plan, execute, and assess the
      outcomes in patients undergoing surgery of the face and neck.

PMID- 15252257
TI  - Importance of facial expression in facial nerve rehabilitation.
AB  - PURPOSE OF REVIEW: This review discusses contemporary evidence for the importance
      of facial expression to human beings. Strategies for management of patients with
      facial nerve dysfunction are discussed. RECENT FINDINGS: The purpose of facial
      expression from a cognitive neuroscience perspective has become clearer,
      including its role in emotional communication and identification. Facial
      retraining may have a role in rehabilitation. SUMMARY: Greater awareness of the
      biologic basis for facial expression may lead us to pay increased attention to
      evaluation and treatment of this component of facial nerve dysfunction. The
      timing of intervention remains important, and many effective techniques exist.

PMID- 15252258
TI  - Nasal reconstruction: the state of the art.
AB  - PURPOSE OF REVIEW: Cutaneous malignancies of the nose are common problems and
      create the need for nasal reconstruction within many otolaryngology practices. In
      spite of the fact that such reconstruction is an ancient art, there continue to
      be innovations and advances that allow for more predictable and functional long
      term results. RECENT FINDINGS: Analyzing the nasal defect through an organized
      algorithm can be useful in many circumstances, especially when one needs to
      consider vectors of tension, minimizing alar base asymmetry, resultant scars, and
      preservation of the intranasal airway. Application of the principle of aesthetic
      subunits has greatly improved the cosmetic results for many large nasal defects,
      and there have been some proposals to modify the original definitions and
      concept. Structural reconstruction is paramount with complex defects that involve
      the nasal framework or with those that are located in functionally critical
      areas. Autogenous cartilage grafting remains the gold standard, but the use of
      alloplastic and homograft materials for grafting continues to be reported as an
      alternative. Internal lining repair is essential with larger defects and the
      versatility of intranasal flaps is understood, but at times not available. Other
      flaps have been described and may be useful on such occasions. SUMMARY: There are
      many considerations during nasal reconstruction, and the surgeon must be facile
      with a variety of options within his/her armamentarium.

PMID- 15252259
TI  - Eyelid reconstruction: the state of the art.
AB  - PURPOSE OF REVIEW: The goals of eyelid reconstruction are corneal protection,
      restoration of the integrity of the lid lamellae, and improvement of facial
      symmetry. Inadequate reconstruction may lead to corneal exposure and sight
      threatening keratopathy; in the younger patient, visual deprivation and amblyopia
      may also follow. The purpose of this review is to describe new materials and
      approaches used in reconstructing the damaged eyelid. RECENT FINDINGS: Although
      the surgical principles of lid reconstruction remain unchallenged, new materials
      and techniques have emerged. These include the use of both autogenous and
      cadaveric acellular dermis in the management of lower eyelid retraction, and
      amniotic membrane transplantation in the management of tarsal conjunctival
      disease. Recent work on upper facial nerve branch reinnervation in the animal
      model may also offer hope for eyelid reanimation after facial palsy. SUMMARY: The
      lid surgeon requires a sound knowledge of the principles involved in
      reconstructing the respective lamellae of the lid. Anterior lamellar
      reconstruction carries a significant risk of ectropion, and large defects may
      require several interposition flaps for optimum skin texture and color
      reconstruction. New materials (autogenous and cadaveric) for posterior lid
      reconstruction may reduce donor site morbidity and surgical time, but they may
      contract significantly after surgery. Recent experience with amniotic membrane
      transplantation may improve the prognosis for patients with entropion and
      symblepharon caused by conjunctival cicatricial changes.

PMID- 15252260
TI  - Skeletal volume enhancement: implants and osteotomies.
AB  - PURPOSE OF REVIEW: Facial plastic surgeons are concerned with improving or
      restoring function and form. Most surgeons perform primarily soft tissue
      procedures, which alone are often sufficient. However, deficiencies in the
      underlying craniomaxillofacial skeleton must also be addressed. Facial skeletal
      augmentation remains an essential aspect of cosmetic and reconstructive surgery.
      This article reviews the basic alloplastic biomaterials available for facial
      volume enhancement, discusses the zygomatic sandwich osteotomy for malar
      augmentation, and describes recent applications of distraction osteogenesis in
      the craniomaxillofacial region. An update in tissue engineering and computer
      modeling is also provided. RECENT FINDINGS: High-porosity expanded
      polytetrafluoroethylene has been developed to provide a softer feel with less
      shrinkage and migration because of better biointegration and cellular ingrowth.
      Long-term results with porous polyethylene have demonstrated superior
      biocompatibility and minimal complications. Hydroxyapatite cement has been
      associated with an immunoguided delayed inflammatory reaction that leads to
      thinning of the overlying skin and exposure of the implant.Applications of
      distraction osteogenesis are rapidly expanding and include deformities of the
      mandible, midface, and cranium. There has been a trend toward the use of internal
      hardware, and internal devices are being developed to deliver a greater degree of
      vector control. Biodegradable devices have been developed to eliminate the second
      surgical procedure necessary for hardware removal. In the future, successful
      tissue engineering could eliminate many of the drawbacks associated with implants
      and osteotomies. The ability to stimulate stem cells to generate autogenous bone
      has been demonstrated in the laboratory. A novel application of computer
      technology that integrates laser surface scanning and digitizing with computer
      aided design and manufacturing to produce facial prostheses has been described.
      SUMMARY: An abundance of alternatives exist for skeletal volume enhancement
      including alloplastic implants, standard osteotomies, and distraction
      osteogenesis. The surgeon must evaluate the pros and cons of each technique in
      the context of each individual patient to determine the most appropriate option.
      Technologic advances in biomaterials, distraction hardware, computer modeling,
      and tissue engineering will continue to supply the surgeon's repertoire with
      improved methods to augment and restore the craniomaxillofacial skeleton.

PMID- 15252261
TI  - Computerized plastic surgery office.
AB  - PURPOSE OF REVIEW: Technology in general and computer capabilities in particular
      are growing at an exponential rate. Keeping current with the latest technological
      capacities and means of incorporating this technology into the facial plastic
      surgeon's office poses a significant challenge. This review will document the
      most appropriate method of incorporation and the latest available technological
      tools. RECENT FINDINGS: Recent developments in wireless networking, systems
      integration, digital photography and video, powerful inexpensive computer
      systems, and the growth of personal digital assistant integration have all
      contributed to a surge in technological advances. Implementing any or all can
      significantly benefit the busy facial plastic surgery office. SUMMARY: Keeping
      abreast of technological advances is a daunting task. Adaptation of these
      advances into the office can at times be overwhelming. This review will assist
      the practicing physician in incorporating selective technological tools to
      streamline his or her systems and increase efficiency.

PMID- 15252262
TI  - Bibliography. Current world literature. Head and neck reconstruction.

PMID- 15252263
TI  - Motor complications in Parkinson disease: a prospective follow-up study.
AB  - Currently, Parkinson disease (PD) can be symptomatically controlled with standard
      treatments; however, after a few years this response typically declines. The
      authors carried out a prospective practice-based study to evaluate the evolution
      and motor complications during the first 5 years in 59 de novo PD patients. They
      observed a significant improvement in UPDRS scores during the first year, then
      the UPDRS mean score declined progressively, especially after the third year
      (UPDRS score at baseline, 27 points; year 1, 19 points; year 2, 20.3 points; year
      3, 22.6 points; year 4, 24.9 points; year 5, 29.5 points). Motor fluctuations,
      dyskinesias, and freezing also increased after year 3 from 10%, 16%, and 8%
      respectively to 35%, 32%, and 27% at year 5. At 5 years, 50% of patients (30 of
      59) still had UPDRS scores better or equal to baseline, and 44% (26 of 59) had no
      motor complications. This latter group represented 38% of those subjects
      initially treated with levodopa and 52% initially treated with other agents.

PMID- 15252264
TI  - Accuracy of objective ambulatory accelerometry in detecting motor complications
      in patients with Parkinson disease.
AB  - Shortcomings of existing assessment methods in Parkinson disease (PD) have led to
      the development of continuous ambulatory multichannel accelerometry for the
      assessment of the core features of PD. Although measures for hypokinesia,
      bradykinesia, and tremor have been validated in groups of patients with PD, it is
      unclear whether this method is able to detect "on" with or without dyskinesias,
      and "off" in individual PD patients. This study therefore addressed the accuracy
      of objective ambulatory accelerometry in detecting motor complications in 15 PD
      patients, using a self-assessment scale as gold standard. Measures for
      hypokinesia, bradykinesia, and tremor showed limited sensitivity (0.60-0.71) and
      specificity (0.66-0.76) for motor complications in individual PD patients. In the
      group of PD patients, comparing the "on" with the "off" state yielded
      statistically significant differences for tremor only. Objective dyskinesia
      measures correlated with time spent with dyskinesias (r = 0.89). Although
      validated for the measurement of hypokinesia, bradykinesia, and tremor,
      continuous ambulatory multichannel accelerometry currently cannot detect "on" and
      "off" in individual PD patients.

PMID- 15252265
TI  - Multicenter, open-label, trial of sarizotan in Parkinson disease patients with
      levodopa-induced dyskinesias (the SPLENDID Study).

PMID- 15252266
TI  - Dopaminergic properties and experimental anti-parkinsonian effects of IPX750 in
      rodent models of Parkinson disease.
AB  - With a view toward improving the neural bioavailability of administered
      dopaminergic compounds, including dopamine, synthetic efforts have been directed
      toward enhancing the brain bioavailability of these compounds by accessing
      cellular sugar transport systems with stereoselective dopaminergic drugs. While
      synthesis and chemistry of the resultant class of compounds has recently been
      described in US Patent No. 6,548,484, the associated biologic properties have not
      previously been reported. One member of this new class, IPX-750, is a pro-drug
      dopamine-gluconamine designed to retain stereospecificity of binding at: glucose
      transporters (GLUT 1/GLUT 3 and intestinal Na/glucose co-transporters SGLT1),
      dopamine transporter (DAT); and, dopaminergic receptors of the D1/D2 families.
      Designed to be cleavable by tissue amidases, results reported here show that
      intact IPX-750 pro-drug retains dopaminergic agonist binding and biologic
      activities both in vitro and in vivo. IPX-750, like dopamine, exhibited
      predominant D5/D1 binding specificity with lower binding activity at D2. As
      expected, binding was highly stereo-specific, ie, IPX-760, a benzamide differing
      in just a hydrogen atom and keto oxygen from IPX-750, bound with 6-fold lower
      activity at D5. In cell culture, activation resulted from binding of IPX-750 at
      D1 or D5 in transfected cells was measured by increased intracellular cAMP.
      Interestingly, considering prior reported in vitro toxicity of dopamine oxidized
      and metabolic product dopamine, no evidence of in vitro toxicity was observed at
      up to 72 hrs in cell cultures at the EC50 of IPX-750 for increasing intracellular
      cAMP. IPX-750 was evaluated in the Parkinson's disease animal models, including
      MPTP mouse model, the 6-hydroxydopamine (6-OHDA) rat model and the Nurr1(+/-)
      knockout mouse model. In MPTP-lesioned and Nurr1+/- knockout mice, IPX-750
      significantly increased Rota-rod time. In 6-OHDA-lesioned rats, IPX-750
      significantly decreased apomorphine (APO)-induced rotation. Worthy of note, after
      cessation of IPX-750 treatments the anti-parkinsonian activity in MPTP-lesioned
      and Nurr1+/- mice required about 2 weeks to washout, suggesting a possible
      biologic reservoir of drug. In addition, after eight weeks of twice daily
      administration of 20 mg/kg IPX-750, mice did not show statistical difference in
      the total number of TH-positive neurons in substantia nigra (SN). These combined
      results suggest (i) that stereo-specific glycoconjugation may be an effective
      method to improve penetrability of drugs through the blood brain barrier; (ii)
      treatment with bioavailable IPX-750 in vitro did not show evidence for
      neurotoxicity; and, (iii) IPX-750 possesses dopaminergic properties and exerts
      anti-parkinsonian effects in three different PD rodent models, suggesting
      therapeutic potential for this new class of drugs in treating dopamine deficiency
      diseases.

PMID- 15252267
TI  - Effects of modafinil on wakefulness and executive function in patients with
      narcolepsy experiencing late-day sleepiness.
AB  - OBJECTIVES: A modafinil daily dosing strategy promotes wakefulness in narcolepsy
      patients experiencing excessive daytime sleepiness; however, some patients may
      continue to experience late-day sleepiness. Excessive sleepiness in narcolepsy is
      associated with cognitive impairment. Modafinil has improved executive function
      in other models of excessive sleepiness. This study evaluated the effects of once
      daily vs. split doses of modafinil on wakefulness and of combined doses on
      executive function in narcolepsy patients experiencing late-day sleepiness
      despite satisfactory modafinil treatment earlier in the day. METHODS: After a 2
      week washout, 24 patients received 3 weeks of double-blind treatment with
      modafinil 400-mg once daily (7 AM) plus placebo (noon) or modafinil 600-mg split
      dose (400 mg, 7 AM; 200 mg, noon). Assessments included a Maintenance of
      Wakefulness Test (MWT) for individual regimens and the Wisconsin Card Sort Test
      (WCST) for treatments combined. RESULTS: Modafinil 600-mg split dose was
      significantly more effective than modafinil 400-mg once daily in improving late
      day MWT scores (5 PM-7 PM; P < 0.05). Significant mean (+/- SEM) reductions from
      baseline of 8.2 +/- 2.7 in the total number of errors and 5.9 +/- 1.9 in total
      percent of errors (P < 0.05, both) were demonstrated for modafinil on the WCST.
      Modafinil was well tolerated; adverse events included headache (n = 1), emotional
      lability (n = 1), bronchitis (n = 1), and accidental injury (n = 2), with no
      reports of insomnia. CONCLUSIONS: For patients with residual late-day sleepiness
      associated with narcolepsy, an additional 200-mg dose of modafinil taken at
      midday was effective in sustaining wakefulness throughout the entire waking day.
      Treatment with modafinil also significantly improved executive function.

PMID- 15252268
TI  - Mycophenolate mofetil in multiple sclerosis.
AB  - OBJECTIVE: To describe experience with the use of mycophenolate mofetil (MMF) in
      the treatment of multiple sclerosis (MS). BACKGROUND: MMF is a potent
      immunosuppressant that is a selective inhibitor of inosine 5'-monophosphate
      dehydrogenase type II, the enzyme responsible for the de novo synthesis of the
      purine nucleotide guanine within activated T and B lymphocytes and macrophages.
      METHODS: A retrospective review of experience in treating 79 MS patients with MMF
      (61 with secondary progressive, 14 with relapsing-remitting, and 4 with primary
      progressive MS) in the authors' MS center. RESULTS: In most cases, MMF was added
      as adjunctive therapy in patients already being treated with either interferon
      beta (n = 44) or glatiramer acetate (n = 20). Fifteen patients not able to use
      interferon or glatiramer acetate were treated with MMF monotherapy. Seventy
      percent of the patients continued MMF therapy. Eight patients discontinued
      therapy because of side effects, 7 patients continued to exhibit evidence of
      disease progression, 4 were denied insurance coverage, 2 were lost to follow-up,
      and 1 patient had an elevation of hepatic transaminases that resolved on
      discontinuation of MMF. One patient discontinued MMF therapy secondary to
      cytomegalovirus diarrhea. CONCLUSION: MMF was well tolerated by the majority of
      patients treated. While these clinical observations were uncontrolled, the
      clinical course of MS was either unchanged or subjectively improved in many of
      the treated patients. A randomized controlled trial of MMF in MS, either as
      monotherapy or in conjunction with interferon or glatiramer acetate, appears
      warranted.

PMID- 15252269
TI  - Clozapine treatment in oromandibular dystonia.
AB  - Oromandibular dystonia (OMD) is a form of focal dystonias, which can be
      associated with substantial disability and is frequently refractory to all
      antidystonic therapies. Clozapine is a dibenzodiazepin derivative atypical
      neuroleptic that has been reported to be effective in the treatment of primary or
      symptomatic dystonia. We report here two patients with severe OMD refractory to
      other antidystonic therapies, who had substantial improvement with clozapine. We
      suggest that clozapine should be considered in patients with OMD who fail to
      response to other treatments.

PMID- 15252270
TI  - Restless legs symptoms in a patient with above knee amputations: a case of
      phantom restless legs.
AB  - We describe a 78-year-old gentleman who, following bilateral above-knee
      amputations, developed symptoms of restless legs syndrome in the absent portions
      of his lower extremities. These symptoms improved with dopamine agonist therapy.
      In addition, he later developed parkinsonism with prominent rest tremor on
      metoclopramide. This suggests that this individual had a dopamine-deficient state
      which predisposed him to both restless legs syndrome and drug-induced or drug
      exacerbated parkinsonism. We propose expanding the spectrum of phantom limb
      phenomena to include phantom restless legs.

PMID- 15252271
TI  - Antidepressants in the treatment of psychosis with comorbid depression in
      Parkinson disease.
AB  - Psychotic symptoms are commonly associated with Parkinson disease and can be a
      source of significant morbidity. Depression has been reported as a comorbidity in
      patients with psychosis. We describe a patient with Parkinson disease with
      psychotic symptoms and comorbid depression whose treatment refractory delusions
      and hallucinations improved markedly only after antidepressant monotherapy was
      initiated. The phenomenology of the delusions was atypical for those found in
      Parkinson or in depression. Psychotic symptoms refractory or only partially
      responsive to conventional treatment should prompt a search for potential
      underlying psychiatric comorbidities. Given case reports of exacerbation of
      psychotic symptoms with antidepressants, we emphasize careful identification and
      active follow up of the comorbid depressive disorders in PD patients with
      psychosis. Potential mechanisms implicated in the response of psychosis to
      antidepressants are discussed.

PMID- 15252272
TI  - Sublingual cocaine: novel recurrence of an ancient practice.
AB  - Present knowledge suggests that cocaine is almost always used by snorting,
      injecting, or smoking. During a recent treatment study, we encountered 2 cases
      who reported active cocaine use by the sublingual route exclusively. We describe
      here 1) the method of sublingual use, 2) its attraction for cocaine dependent
      individuals, especially those who wish to conceal use, and 3) concerns regarding
      the medical consequences of sublingual cocaine use. Sublingual cocaine use may
      cause unique medical symptoms and may easily evade detection by medical
      personnel.

PMID- 15252273
TI  - A case of L-dopa-responsive parkinsonian syndrome after low-dose oral
      methotrexate intake.

PMID- 15252274
TI  - Ziprasidone and weight gain.
AB  - We describe the case of a 12-year-old white male in whom significant weight gain
      occurred within 3 months of treatment with Ziprasidone. It is important that
      clinicians are aware of this possibility since this medication is marketed as one
      of the few antipsychotic medications not associated with significant weight gain.

PMID- 15252275
TI  - Effects of dopamine D3 receptor antagonists on spontaneous and agonist-reduced
      motor activity in NMRI mice and Wistar rats: comparative study with nafadotride,
      U 99194A and SB 277011.
AB  - Studies investigating the role of the dopamine D3 receptor in the regulation of
      motor activity of rodents have used several ligands; however, there have been few
      comparative studies using agonist-antagonist interactions. In the present study,
      we compared the effects of dopamine D3 antagonists with different levels of
      selectivity over D2 receptors (nafadotride, U 99194A and SB 277011) on motor
      activity as well as on agonist-induced hypoactivity, in mice and rats. Horizontal
      and vertical movements were measured in photocell activity cages. 7-Hydroxy-2-(di
      n-propylamino)tetralin (7-OH-DPAT) and PD 128907 were used as dopaminergic
      agonists. Both dose-dependently inhibited motor activity in mice and vertical
      activity in rats, while decreasing horizontal activity of rats at doses of 0.01
      and 0.1 mg/kg s.c., with no effect (7-OH-DPAT) or stimulation (PD 128907) at the
      1 mg/kg dose. In mice habituated to the activity cage, nafadotride (0.1-3 mg/kg
      i.p.) caused a dose-dependent decrease in motor activity but did not affect the
      hypomotility evoked by either 7-OH-DPAT (0.1 mg/kg) or PD 128907 (0.1 mg/kg). In
      habituated rats it had no significant effect on motor activity and was not able
      to antagonize the hypoactivity caused by PD 128907 (0.1 mg/kg s.c.). U 99194A (5,
      10 and 20 mg/kg s.c.) dose-dependently and significantly increased motor activity
      in mice and inhibited the effects of both agonists. In rats, nafadotride produced
      considerable motor stimulation and significantly inhibited the PD 128907-induced
      decrease in horizontal, but not in vertical, activity. SB 277011 (15-45 mg/kg
      p.o.) significantly increased motor activity in mice and partially blocked the
      action of 7-OH-DPAT on vertical, but not on horizontal, activity while against PD
      128907, its significant inhibitory effect was restricted to a single dose (20
      mg/kg). In habituated rats, SB 277011 (13.5, 20 and 30 mg/kg p.o.) exerted no
      significant effects on motor activity and did not antagonize the hypoactivity
      caused by PD 128907. Considerable species differences and movement-type
      differences (horizontal versus vertical) were observed between the effects of the
      tested dopamine D2/D3 ligands on motor activity in rodents. The antagonists also
      differed markedly in the robustness of their action. The poorly D3 selective
      antagonist, nafadotride, had little effect on motor behaviour. The moderately
      selective U 99194A exerted marked stimulatory effects on motility, and potently
      inhibited the actions of agonists. SB 277011, a highly selective dopamine D3
      receptor antagonist, showed limited ability to influence the motor activity of
      rodents.

PMID- 15252276
TI  - Effects of NMDA receptor channel blockers, MK-801 and memantine, on locomotor
      activity and tolerance to delay of reward in Wistar-Kyoto and spontaneously
      hypertensive rats.
AB  - N-Methyl-D-aspartate (NMDA) receptor blockade enhances motor activity and
      stimulates dopamine metabolism, effects shared with classical psychostimulant
      drugs. The present study aimed to characterize behavioral effects of two NMDA
      receptor channel blockers, MK-801 and memantine, in both Wistar-Kyoto (WKY) and
      spontaneously hypertensive (SHR) rats. In Experiment 1, SHR rats demonstrated
      higher spontaneous locomotor activity and spent more time in the central area of
      the open field apparatus compared with WKY rats. Rats of both strains pre-treated
      with MK-801 (0.01-0.3 mg/kg) or memantine (1-32 mg/kg) demonstrated dose
      dependent increases in the total distance traveled and time spent in the central
      area. Experiment 2 was based on the two-lever discrete-trial delayed
      reinforcement task in which rats could press one lever to obtain one pellet
      immediately or another lever for four pellets delivered after a variable delay (0
      60 s). Tolerance to delay of reward did not differ between strains. MK-801 (0.03
      0.3 mg/kg) and memantine (1-10 mg/kg) produced small, but significant,
      facilitation of the large-reward lever responding and markedly impaired operant
      performance at higher dose levels (increased number of missed trials). For both
      experiments, effects of MK-801 and memantine were more pronounced in WKY compared
      with SHR rats. Additional studies are needed to address the utility of
      noncompetitive NMDA receptor blockers in the treatment of attention deficit and
      hyperactivity disorder.

PMID- 15252277
TI  - The NMDA receptor channel blocker memantine and opioid receptor antagonist
      naltrexone inhibit the saccharin deprivation effect in rats.
AB  - Several drugs, such as N-methyl-D-aspartate (NMDA) receptor channel blockers
      (memantine), naltrexone (but not naloxone) and acamprosate, have previously been
      reported to attenuate the expression of the alcohol deprivation effect, a
      phenomenon seen as an increase in post-deprivation alcohol consumption. The
      present study aimed to evaluate the effects of these drugs on the development and
      expression of the saccharin deprivation effect in adult male Wistar rats.
      Memantine (13 mg/kg per day) and naltrexone (5 mg/kg, twice daily), but not
      naloxone (24 mg/kg per day) or acamprosate (200 mg/kg, twice daily), prevented
      the increase in the consumption of saccharin after a 1-week deprivation from free
      choice, unlimited access to saccharin (0.1%, w/v). Taken together with the
      results of previous studies, these results suggest that naltrexone and memantine
      attenuate the expression of both the alcohol and saccharin deprivation effects.

PMID- 15252278
TI  - Ethanol-maintained responding of rats is more resistant to change in a context
      with added non-drug reinforcement.
AB  - Alternative non-drug reinforcers reliably decrease drug-maintained responding in
      self-administration procedures. Studies of the resistance to change of food
      maintained behavior, however, have found that responding in the presence of a
      stimulus associated with an alternative reinforcer is more resistant to
      disruption. This increase in persistence occurs despite lower response rates when
      the alternative reinforcer is present. The present experiment examined if, in
      addition to decreasing response rates, an alternative non-drug reinforcer also
      increases the persistence of drug-maintained responding. Rats self-administered
      oral ethanol in a multiple schedule of reinforcement in which responding was
      reinforced in two components signaled by different stimuli. In one component,
      response-independent food was delivered in addition to the earned ethanol. The
      effects of the alternative food reinforcer on response rates and resistance to
      extinction in the two components were examined. As in previous experiments on the
      resistance to change of food-maintained operant behavior, response rates were
      lower, but more resistant to extinction in the presence of the stimulus
      associated with the alternative reinforcer. These findings suggest that all the
      reinforcers obtained in a context in which drugs are consumed may contribute to
      the persistence of drug seeking in that context. This increase in persistence may
      occur even if the alternative reinforcers interfere with drug seeking.

PMID- 15252279
TI  - Working memory deficits in adult rats after prenatal disruption of neurogenesis.
AB  - We investigated the cognitive consequences of a prenatal injection of the mitotic
      inhibitor methylazoxymethanol (MAM) into pregnant rats at embryonic day 15 (E15)
      or 17 (E17). The male offspring were tested when adult on a version of the radial
      arm maze task that assesses spatial working memory with an extended delay, where
      performance is dependent, in part, on the hippocampal-prefrontal circuit. A major
      impairment of spatial learning was observed in E15 MAM rats. However, the E17 MAM
      rats did learn the rule but were impaired selectively in the 30-min delay
      interposed task. Morphologically, the E15 MAM rats exhibited dramatic gross brain
      abnormalities, whereas the E17 MAM animals displayed aberrant cell migration in
      the hippocampus and a disrupted laminar pattern in the neocortex. These results
      suggest that late gestational MAM injection (E17) causes a cognitive impairment
      in a prefrontal cortex-hippocampus-dependent working memory task. This approach
      could provide a new developmental model of disorders associated with working
      memory deficits, such as schizophrenia.

PMID- 15252280
TI  - Influence of beta-adrenoceptor agonists and antagonists on baclofen-induced
      memory impairment in mice.
AB  - Post-training administration of different doses of baclofen (a GABAB agonist) has
      been shown to impair memory retention, in a step-down passive avoidance test in
      mice. We have studied the effects of beta-adrenergic agonists and antagonists on
      baclofen-induced memory impairment in mice. Dobutamine (a beta 1-agonist) or
      salbutamol (a beta 2-agonist) reversed the memory impairment induced by baclofen
      without exhibiting intrinsic actions on memory when administered alone. The
      administration of atenolol (a beta 1-antagonist) or propranolol (a beta
      antagonist) produced a memory impairment. When co-administered with baclofen,
      both atenolol and propranolol exacerbated the memory impairment induced by the
      GABAB agonist. It is concluded that beta-adrenergic mechanisms may be involved in
      the modulation of memory via GABAB receptors.

PMID- 15252281
TI  - CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and
      pharmacological evidence with CB1-specific agents.
AB  - Cannabinoids are known to modulate GABAergic and glutamatergic transmission in
      cortical areas, the former via CB1 and the latter via a novel receptor.
      Pharmacological data demonstrate that several widely used cannabinoid ligands
      bind to both receptors, which may explain the inconsistencies in their
      behavioural effects. Earlier we showed that the cannabinoid antagonist SR-141716A
      affected behaviour in both CB1 knockout and wild-type animals, and its effect
      (anxiolysis) was different from that of CB1 gene disruption (anxiogenesis). In
      the present experiments, we studied the effects of the CB1 antagonist AM-251, and
      the cannabinoid agonist WIN-55,212-2 in wild-type as well as in CB1 knockout
      mice. CB1 knockout mice showed higher scores of anxiety-like behaviour than the
      wild-type animals in the elevated plus-maze. Selective blockade of CB1 receptors
      by AM-251 (0.3, 1 and 3 mg/kg) increased anxiety-like behaviour dose-dependently
      in the wild-type mice but had no effect in the knockouts. In wild types, the
      cannabinoid agonist WIN-55,212-2 (1 and 3 mg/kg) caused a decrease in anxiety
      like behaviour, which was abolished by the CB1-selective antagonist AM-251 (3
      mg/kg). The same agonist did not change plus-maze behaviour in CB1 knockout
      animals. These data demonstrate at the behavioural level that AM-251 and, at low
      concentrations, WIN-55,212-2, are selective ligands of the CB1 cannabinoid
      receptor in mice. Our studies on the behavioural effects of the cannabinoid
      antagonist SR-141716A and the CB1 antagonist AM-251 show that the CB1 and the
      novel cannabinoid receptor mediate anxiolytic and anxiogenic effects,
      respectively. This suggests that agonists of the former, or antagonists of the
      latter, are promising new compounds in the pharmacotherapy of anxiety.

PMID- 15252282
TI  - Acute marijuana effects on response-reinforcer relations under multiple variable
      interval schedules.
AB  - Acute marijuana administration may alter response-reinforcer relationships via a
      change in reinforcer efficacy, but may also impair coordination and motor
      function. One approach to evaluating drug effects on both motor function and
      reinforcer efficacy involves fitting the matching law equation to data obtained
      under multiple variable interval (VI) schedules. The present report describes an
      experiment that examined the effects of acute marijuana on response properties
      using this approach. Six human subjects responded under a multiple VI schedule
      for monetary reinforcers after smoking placebo and two active doses of marijuana.
      The low marijuana dose produced unsystematic changes in responding. As measured
      by the matching law equation parameters (k and rB), at the high dose five
      subjects showed a decrease-motor-related properties of response rate and four
      subjects' responding indicated a decrease in reinforcer efficacy. These data
      raise the possibility that, at high doses, marijuana administration alters both
      motor function and reinforcer efficacy.

PMID- 15252283
TI  - Association of functional opioid receptor genotypes with alcohol dependence in
      Koreans.
AB  - BACKGROUND: The functional polymorphism (A118G) of the mu-opioid receptor gene
      (OPRM1) is thought to have clinical significance in the treatment of alcohol
      dependence. This study compared Koreans with one or two copies of the A118G
      polymorphism seeking treatment for alcohol dependence with a group of non-alcohol
      dependent controls. METHODS: Patients hospitalized for alcohol dependence (n =
      112) and a group of non-alcohol-dependent controls (n = 140) were interviewed on
      aspects of drinking history and psychiatric history. Patients and controls were
      excluded if they met criteria for any other major psychiatric disorder.
      Participants were genotyped at the OPRM1 locus. RESULTS: The allele frequency of
      the Asp40 allele was 0.397 in the alcohol-dependent group, which is consistent
      with other literature demonstrating this polymorphism to be common in Asian
      populations. Within the alcohol-dependent subjects, being homozygous for the
      Asp40 allele was associated with more days drinking than those heterozygous or
      homozygous for the Asn40 allele. Differences in the allele frequencies between
      alcohol-dependent and non-alcohol-dependent controls were not significant.
      CONCLUSIONS: These results suggest that having one or two copies of the A118G
      allele is common among Koreans and may be an important genetic factor in the
      etiology of alcohol dependence and the frequency of alcohol consumption.

PMID- 15252284
TI  - Characterization of acute functional tolerance to the hypnotic effects of ethanol
      in mice.
AB  - BACKGROUND: Acute functional tolerance (AFT) to ethanol-induced hypnosis is one
      of the main factors that affect the duration of ethanol-induced loss of righting
      reflex (LRR: "sleep time"). Investigators who use duration of LRR as a measure of
      ethanol-induced sedation should consider the potential magnitude and time course
      of this neuroadaptation when interpreting their results. However, AFT to the
      hypnotic effects of ethanol has not been well characterized. The present study
      explored this form of AFT using a novel method of monitoring LRR in mice.
      METHODS: Genetically heterogeneous mice were used to study effects of dose and
      time on the development of AFT. Mice were treated with different dose regimens
      and tested for LRR after hypnotic doses using a cylindrical restrainer. Measures
      of initial sensitivity and AFT to ethanol-induced hypnosis were calculated and
      analyzed. Inbred strains of mice were then characterized for AFT magnitude after
      a single ethanol dose. RESULTS: Results showed that (a) AFT developed in a dose
      dependent fashion but attained an apparent maximum value; (b) AFT to ethanol
      induced hypnosis could develop partially after a small, subhypnotic dose; (c) AFT
      developed very rapidly and approached its maximum for a given dose by the 10th
      min after injection of ethanol; and (d) AFT has a strong genetic component.
      CONCLUSION: Although specific for AFT to the hypnotic effects of ethanol, the
      present findings expand general knowledge about acute tolerance and should also
      be useful for investigators who use loss of righting reflex as a measure of
      ethanol sensitivity.

PMID- 15252285
TI  - Desensitization of PKA-stimulated ciliary beat frequency in an ethanol-fed rat
      model of cigarette smoke exposure.
AB  - BACKGROUND: Our previous studies have shown that the ciliary beat frequency (CBF)
      of cultured ciliated airway epithelial cells exposed to chronic ethanol fails to
      increase in response to beta-agonist stimulation. This loss of the ciliary
      "flight response" correlates with an ethanol-mediated desensitization of
      adenosine 3':5'-cyclic monophosphate-dependent protein kinase (PKA), a known
      regulatory component of CBF stimulation. We hypothesized that a similar ethanol
      mediated desensitization of CBF would occur in vivo. METHODS: Sprague Dawley rats
      were fed a liquid diet containing various concentrations of ethanol for 1 or 5
      weeks. Half were exposed to cigarette smoke for 12 weeks and half were sham
      exposed. Animals were killed and tracheal epithelial cells analyzed for CBF and
      PKA activity. RESULTS: Baseline CBF (approximately 6 Hz) was unchanged in
      tracheal epithelial cells of rats consuming diets containing 0-36% ethanol for 5
      weeks. Isoproterenol stimulated CBF to 12 to 13 Hz in the tracheal epithelial
      cells of control rats not administered ethanol. However, isoproterenol
      stimulation of CBF was blunted to 7.5 Hz in rats eating a 26% ethanol diet, and
      there was no stimulation of CBF in rats fed a diet containing 36% ethanol.
      Similarly, isoproterenol stimulated a 2- to 3-fold increase in PKA activity in
      control rats, but this PKA response to isoproterenol was blunted in rats fed
      increasing concentrations of ethanol. No isoproterenol-stimulated PKA response
      was observed in rats fed 36% ethanol. No ethanol-induced changes in cyclic
      guanosine monophosphate-dependent protein kinase or protein kinase C were
      observed in the rats' tracheal epithelial cells. Cigarette smoke exposure
      slightly elevated baseline CBF and lowered the ethanol consumption level for
      isoproterenol-desensitization of CBF and PKA activation to 16%. No isoproterenol
      desensitization was observed after 1 week of alcohol feeding. Furthermore, 36%
      ethanol-feeding for 1 week stimulated rat tracheal CBF and PKA. CONCLUSION: These
      data demonstrate that in vivo administration of ethanol to rats results in
      decreased ciliary beating and the desensitization of PKA. This suggests a
      mechanism for mucociliary clearance dysfunction in alcoholics.

PMID- 15252286
TI  - Dose-dependent activation of Ca2+-activated K+ channels by ethanol contributes to
      improved endothelial cell functions.
AB  - BACKGROUND: Regular moderate alcohol (EtOH) intake seems to protect against both
      coronary artery disease and ischemic stroke, whereas the risk increases with
      heavy EtOH consumption. Effects of EtOH on endothelial cell function may be
      relevant to these disparate effects. Potassium channels play an important role in
      the regulation of endothelial cell functions. Therefore, we investigated whether
      Ca-activated K channels (BKCa) are modulated by EtOH. Furthermore, we examined
      whether EtOH-induced changes of endothelial nitric oxide (NO) formation and cell
      proliferation are due to BKCa activation. METHODS: The patch-clamp technique was
      used to investigate BKCa activity in cultured human umbilical vein endothelial
      cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5
      diaminofluorescein. Endothelial proliferation was examined by using cell counts
      and measuring [H]thymidine incorporation. RESULTS: EtOH dose-dependently (10-150
      mmol/liter) modulated BKCa-activity, with the highest increase of open-state
      probability at a concentration of 50 mmol/liter (n = 13; p < 0.05). Inside-out
      recordings revealed that this effect was due to direct BKCa activation, whereas
      open-state probability was not changed in cell-attached recordings after
      pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant
      increase of NO levels, which was blocked by the highly selective BKCa inhibitor
      iberiotoxin (100 nmol/l; n = 30; p < 0.05). Higher concentrations of EtOH (100
      and 150 mmol/liter) significantly reduced NO synthesis (n = 30; p < 0.05). Both
      methods revealed a significant increase of HUVEC proliferation, which was
      inhibited by iberiotoxin (n = 30; p < 0.05). At a concentration of 150
      mmol/liter, EtOH caused a significant reduction of endothelial proliferation.
      CONCLUSIONS: EtOH directly activates BKCa in HUVEC, leading to an increase of
      endothelial proliferation and production of NO. These results indicate a possible
      beneficial effect of low-dose EtOH on endothelial function, whereas higher
      concentrations must be considered as harmful.

PMID- 15252287
TI  - Anxiety-like behavior in mice in two apparatuses during withdrawal from chronic
      ethanol vapor inhalation.
AB  - BACKGROUND: Anxiety during ethanol withdrawal may be a factor in relapse to
      alcohol abuse and dependence. Animal models of ethanol withdrawal have typically
      used forced consumption of an ethanol-containing liquid diet to induce
      dependence. Ethanol vapor inhalation offers an advantage over liquid diet
      consumption in that the onset of withdrawal can be temporally controlled more
      precisely, allowing studies of the development of withdrawal symptoms. METHODS:
      The purpose of the current study was to induce ethanol dependence in mice using
      an inhalation procedure and to assess withdrawal anxiety symptoms behaviorally in
      the elevated zero maze and in the light/dark box. Male and female mice were
      exposed to 3 days of ethanol vapors. Anxiety-like behavior was measured on the
      elevated zero maze and light/dark box at multiple time points during withdrawal.
      RESULTS: Mice experiencing ethanol withdrawal demonstrated increased anxiety-like
      behaviors relative to control animals in both apparatuses. However, this finding
      was specific to the procedure used with the elevated zero maze and was strongly
      influenced by sex in the light/dark box. CONCLUSIONS: Ethanol vapor inhalation
      appears to be a valid tool for the study of withdrawal-induced anxiety.

PMID- 15252288
TI  - Developmental alcohol exposure alters light-induced phase shifts of the circadian
      activity rhythm in rats.
AB  - BACKGROUND: Developmental alcohol (EtOH) exposure produces long-term changes in
      the photic regulation of rat circadian behavior. Because entrainment of circadian
      rhythms to 24-hr light/dark cycles is mediated by phase shifting or resetting the
      clock mechanism, we examined whether developmental EtOH exposure also alters the
      phase-shifting effects of light pulses on the rat activity rhythm. METHODS:
      Artificially reared Sprague-Dawley rat pups were exposed to EtOH (4.5 g/kg/day)
      or an isocaloric milk formula (gastrostomy control; GC) on postnatal days 4 to 9.
      At 2 months of age, rats from the EtOH, GC, and suckle control groups were housed
      individually, and wheel-running behavior was continuously recorded first in a 12
      hr light/12-hr dark photoperiod for 10 to 14 days and thereafter in constant
      darkness (DD). Once the activity rhythm was observed to stably free-run in DD for
      at least 14 days, animals were exposed to a 15-min light pulse at either 2 or 10
      hr after the onset of activity [i.e., circadian time (CT) 14 or 22,
      respectively], because light exposure at these times induces maximal phase delays
      or advances of the rat activity rhythm. RESULTS: EtOH-treated rats were
      distinguished by robust increases in their phase-shifting responses to light. In
      the suckle control and GC groups, light pulses shifted the activity rhythm as
      expected, inducing phase delays of approximately 2 hr at CT 14 and advances of
      similar amplitude at CT 22. In contrast, the same light stimulus produced phase
      delays at CT 14 and advances at CT 22 of longer than 3 hr in EtOH-treated rats.
      The mean phase delay at CT 14 and advance at CT 22 in EtOH rats were
      significantly greater (p < 0.05) than the light-induced shifts observed in
      control animals. CONCLUSIONS: The data indicate that developmental EtOH exposure
      alters the phase-shifting responses of the rat activity rhythm to light. This
      finding, coupled with changes in the circadian period and light/dark entrainment
      observed in EtOH-treated rats, suggests that developmental EtOH exposure may
      permanently alter the clock mechanism in the suprachiasmatic nucleus and its
      regulation of circadian behavior.

PMID- 15252289
TI  - Differential increase in taurine levels by low-dose ethanol in the dorsal and
      ventral striatum revealed by microdialysis with on-line capillary
      electrophoresis.
AB  - Ethanol increases taurine efflux in the nucleus accumbens or ventral striatum
      (VS), a dopaminergic terminal region involved in positive reinforcement. However,
      this has been found only at ethanol doses above 1 g/kg intraperitoneally, which
      is higher than what most rats will self-administer. We used a sensitive on-line
      assay of microdialysate content to test whether lower doses of ethanol
      selectively increase taurine efflux in VS as opposed to other dopaminergic
      regions not involved in reinforcement (e.g., dorsal striatum; DS). Adult male
      rats with microdialysis probes in VS or DS were injected with ethanol (0, 0.5, 1,
      and 2 g/kg intraperitoneally), and the amino acid content of the dialysate was
      measured every 11 sec using capillary electrophoresis and laser-induced
      fluorescence detection. In VS, 0.5 g/kg ethanol significantly increased taurine
      levels by 20% for 10 min. A similar increase was seen after 1 g/kg ethanol, which
      lasted for about 20 min after injection. A two-phased taurine efflux was observed
      with the 2.0 g/kg dose, where taurine was increased by 2-fold after 5 min but it
      remained elevated by 30% for at least 60 min. In contrast, DS exhibited much
      smaller dose-related increases in taurine. Glycine, glutamate, serine, and gamma
      aminobutyric acid were not systematically affected by lower doses of ethanol;
      however, 2 g/kg slowly decreased these amino acids in both brain regions during
      the hour after injection. These data implicate a possible role of taurine in the
      mechanism of action of ethanol in the VS. The high sensitivity and time
      resolution afforded by capillary electrophoresis and laser-induced fluorescence
      detection will be useful for detecting subtle changes of neuronally active amino
      acids levels due to low doses of ethanol.

PMID- 15252290
TI  - Nursing from an ethanol-intoxicated dam induces short- and long-term disruptions
      in motor performance and enhances later self-administration of the drug.
AB  - RATIONALE: During interactions with an ethanol-intoxicated dam, preweanling rats
      encode ethanol-related chemosensory information. These experiences have been
      observed to enhance subsequent recognition of ethanol's chemosensory properties
      and to modulate learning about ethanol. OBJECTIVE: The present study tested the
      effects of ethanol-related nursing experiences on motor function in later infancy
      and adolescence and on ethanol intake during adolescence. METHODS: Wistar-derived
      rats were reared by dams intragastrically administered with ethanol (2.5 g/kg) or
      with water during postnatal days (PDs) 3, 5, 7, 9, 11, and 13. Later in infancy
      or in adolescence, these rats were tested on a motor coordination task
      (Accelerod) while either sober or acutely intoxicated with ethanol (1 g/kg).
      During adolescence, animals had simultaneous access to varying ethanol
      concentrations (3, 4, 5, or 6% v/v) and water. RESULTS: Both infants and
      adolescents that had been reared by ethanol-intoxicated dams exhibited dramatic
      behavioral impairments in the Accelerod task when compared with the offspring of
      water control dams. Ethanol intoxication disrupted motor performance in both age
      groups, but this effect was independent of prior maternal treatment. When tested
      for voluntary ethanol intake as adolescents, those with prior nursing experiences
      with an intoxicated dam ingested more ethanol than adolescents reared by sober
      dams. CONCLUSIONS: Early experiences with alcohol comprising interactions with an
      alcohol-intoxicated dam result in motor impairment and enhanced ethanol intake
      later in life.

PMID- 15252291
TI  - Naltrexone depot for treatment of alcohol dependence: a multicenter, randomized,
      placebo-controlled clinical trial.
AB  - BACKGROUND: Studies of the efficacy of naltrexone for alcohol dependence have
      yielded variable findings, which may be due, in part, to variation in compliance
      with oral naltrexone. Efforts to improve naltrexone compliance have included the
      development of injectable, long-acting depot formulations. METHODS: We conducted
      a multicenter trial in 315 subjects who were randomly assigned to receive an
      intramuscular injection of a depot formulation containing naltrexone (n = 158) or
      a placebo formulation (n = 157) monthly for 3 months. All patients received five
      sessions of manual-guided motivational enhancement therapy during the 12 weeks of
      the study. The outcomes of interest were based on self-reported alcohol use and
      gamma-glutamyl transpeptidase level. Missing data or data from subjects who
      discontinued the study were conservatively treated as heavy-drinking days.
      RESULTS: Groups were comparable on pretreatment demographic and clinical
      measures. The medication was well tolerated; 73.7% of subjects received all
      injections. The time to the first heavy-drinking day, the percentage of subjects
      with no heavy drinking throughout the study, and gamma-glutamyl transpeptidase
      levels favored the naltrexone depot, although the effects did not reach
      statistical significance. There was a significant advantage for naltrexone depot
      treatment on the time to the first drinking day. Naltrexone depot subjects also
      had significantly fewer drinking days during treatment and a significantly
      greater abstinence rate than the placebo group (18% vs. 10%). CONCLUSIONS: This
      is the first multicenter study of a depot formulation of naltrexone for the
      treatment of alcohol dependence. Using a conservative intent-to-treat analysis,
      the study showed an advantage for the active medication. Further research with
      this formulation is warranted.

PMID- 15252292
TI  - Using daily interactive voice response technology to measure drinking and related
      behaviors in a pharmacotherapy study.
AB  - BACKGROUND: Interactive voice response technology (IVR) allows investigators to
      collect daily measures of drinking, medication adherence, mood, and other
      treatment-relevant variables that may change day to day during a clinical trial.
      Despite these advantages, no published studies have used IVR in alcohol
      pharmacotherapy trials. METHODS: Subjects provided daily data via IVR during the
      12-week treatment period. Seven subjects completed the trial. RESULTS: We found a
      high level of participant adherence to the IVR protocol, higher levels of
      drinking reported by IVR than by a commonly used recall method, and distinct
      within-day associations between daily mood and alcohol consumption: these could
      not be obtained through traditional assessment methods. CONCLUSIONS: IVR seems to
      be feasible for the collection of daily indicators of treatment outcomes and
      processes in pharmacotherapy studies among problem drinkers.

PMID- 15252293
TI  - Treatment outcomes in type A and B alcohol dependence 6 months after serotonergic
      pharmacotherapy.
AB  - BACKGROUND: Evidence supporting the use of serotonergic medications for the
      treatment of alcohol dependence is available from studies where pharmacotherapy
      targeted specific alcoholic subtypes. We previously established with Babor's
      alcohol typology that type A "lower risk/severity" alcoholics (n = 55) had better
      treatment response to 14 weeks of sertraline (200 mg/day) than placebo, and this
      was not found for type B "higher risk/severity" alcoholics (n = 45). The purpose
      of this study was to assess in this original study group whether treatment gains
      in the type A alcoholics were maintained or whether treatment outcomes changed
      for the type B alcoholics after discontinuing pharmacotherapy. METHODS: After the
      end of a 3-month course of 200 mg/day sertraline, the subjects were interviewed
      at several time points about their alcohol drinking, if any, using the timeline
      follow-back method. For 90% of the original study group, mixed effects and
      generalized estimating equation models were used to compare monthly drinking
      amounts over a 6-month posttreatment period with drinking amounts in the last
      month of treatment. RESULTS: We found that type A alcoholics who had been treated
      with sertraline, in contrast to placebo, maintained the good outcomes they had
      achieved during treatment for at least 6 months after pharmacotherapy. We found
      that type B alcoholics who had been treated with sertraline, in contrast to
      placebo, continued to show no advantage for pharmacotherapy in the 6 months after
      completing treatment. In addition, heavy drinking in type B alcoholics increased
      over the 6 months postpharmacotherapy in those initially treated with sertraline
      compared with placebo. CONCLUSIONS: These data support the importance of
      considering alcohol subtype when pharmacologically treating alcohol dependence.

PMID- 15252295
TI  - Alcohol intake, type of beverage, and risk of breast cancer in pre- and
      postmenopausal women.
AB  - BACKGROUND: Most studies of the relation between alcohol consumption and breast
      cancer have shown a modestly increased risk, although the results are still
      conflicting. METHODS: The aim of this prospective population-based cohort study
      was to assess the influence of alcohol intake and type of beverage (beer, wine,
      or spirits) on breast cancer risk in relation to menopausal status. Among 13,074
      women aged 20 to 91 years, we examined the relationship between breast cancer
      risk, total alcohol intake, and type of alcohol in relation to menopausal status.
      The women were classified as premenopausal or as postmenopausal at younger than
      70 years or 70 years or more. RESULTS: During follow-up, 76 premenopausal and 397
      postmenopausal women developed breast cancer. Premenopausal women who had an
      intake of more than 27 drinks per week had a relative risk of breast cancer of
      3.49 (95% confidence limits, 1.36-8.99) compared with light drinkers (p = 0.011),
      whereas there were no differences in risk in the lower-intake categories. The
      increased risk of breast cancer among premenopausal women was independent of the
      type of alcohol. Postmenopausal women older than 70 years of age who had an
      intake of more than six drinks per week of spirits had a relative risk of breast
      cancer of 2.43 (95% confidence limits, 1.41-4.20) compared with women who
      consumed less than one drink of spirits per week (p = 0.0014). CONCLUSIONS: Total
      alcohol intake of more than 27 drinks per week increases breast cancer risk in
      premenopausal women independently of the type of alcohol. Among postmenopausal
      women, an intake of spirits of more than six drinks per week increases breast
      cancer risk.

PMID- 15252294
TI  - Alcohol effects during acamprosate treatment: a dose-response study in humans.
AB  - BACKGROUND: Acamprosate (calcium acetyl homotaurinate) reduces alcohol intake in
      animals and increases abstinence rates in alcohol-dependent persons.
      Acamprosate's mechanism of action, however, remains poorly understood. In order
      to examine whether acamprosate/alcohol interactions contribute to acamprosate's
      efficacy, the present double-blind, placebo-controlled human laboratory study
      examined effects of acamprosate on the pharmacokinetics and subjective,
      psychomotor, and physiological effects of alcohol in heavy drinkers. METHODS: In
      a six-week within-subject design, participants were maintained on acamprosate (0,
      2, and 4 g, p.o., double-blind, in counterbalanced order) for 11 days at each
      dose. Physiological, subjective, and psychomotor measures were collected daily
      during each dosing cycle. During each acamprosate dose condition, subjects were
      challenged with 0, 0.5, and 1.0 g/kg ethanol (p.o., counterbalanced order) during
      three separate laboratory sessions. Subjective, physiological, and psychomotor
      effects of alcohol, and breath alcohol levels were collected at baseline and at
      30-min intervals for a 3-hr post-administration period. RESULTS: Acamprosate
      alone did not substantially affect subjective, physiological, or psychomotor
      performance measures. Acamprosate did not alter alcohol pharmacokinetics, or
      alcohol-induced behavioral impairment or tachycardia, and most subjective alcohol
      effects were also unaltered by acamprosate as well. Although a trend appeared for
      acamprosate to increase subjective ratings of intoxication following the lower
      (0.5 g/kg) alcohol dose, adjustment for individual differences in blood alcohol
      level eliminated this effect, suggesting the trend was not due to a central
      effect of acamprosate. CONCLUSIONS: Acamprosate does not alter alcohol
      pharmacokinetics, acute physiological or psychomotor alcohol effects, or most
      subjective alcohol effects.

PMID- 15252296
TI  - Adipogenic effect of alcohol on human bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: In addition to a decrease in bone mass in alcoholics their osteopenic
      skeletons show an increase in bone marrow adiposity. Human bone marrow
      mesenchymal stem cells (hMSC) in vivo differentiate into several phenotypes
      including osteogenic and adipogenic cells, both of which remain as resident
      populations of bone marrow. In vitro, the lineage commitment and differentiation
      of hMSC toward the adipogenic pathway can be promoted by alcohol. METHODS: Human
      male and female mesenchymal stem cells from joint replacement surgery were
      cultured. Cells were grouped as: 1) Control (no additions to the culture medium),
      2) EtOH (50 mm alcohol added to the culture medium), 3) OS (osteogenic inducers
      added to the culture medium), and 4) OS + EtOH (osteogenic inducers and 50 mm
      alcohol added to the culture medium). Cultures stained with Nile Red confirmed
      the development of differentiated adipocytes. Population analysis was performed
      using fluorescence-activated cell sorting. Gene expression of early, middle,
      late, and terminal differentiation stage markers (PPAR)gamma2, lipoprotein
      lipase, adipsin, leptin, and adipocyte P2 (aP2)] was studied by Northern
      hybridization, and protein synthesis of aP2 was determined by Western analysis.
      RESULTS: Nile red staining confirmed increased adipocyte development 10 days
      after the onset of treatment with 50 mm alcohol and osteogenic induction. By day
      21 the number of adipocytes increased to 13.6% of the total population. Alcohol
      up-regulated the gene expression of PPARgamma2 whereas no up-regulation was
      observed for the other genes. Protein production of aP2 was significantly
      increased in hMSC cells by culture in the presence of alcohol. CONCLUSIONS: The
      data suggest that alcohol's adipogenic effect on cultured hMSC is through up
      regulation of PPARgamma2 at the point of lineage commitment as well as through
      enhancement of lipid transport and storage through increased aP2 synthesis. The
      alcohol-induced expression and synthesis changes account for the increased Nile
      red staining of cultured hMSC.

PMID- 15252297
TI  - In heavy drinkers fatty acid ethyl esters in the serum are increased for 44 hr
      after ethanol consumption.
AB  - BACKGROUND: Fatty acid ethyl esters (FAEEs) have been proposed as a marker of
      ethanol consumption because they can be detected for up to 24 hr after a moderate
      intake of ethanol, even though blood ethanol remains increased for only 8 hr.
      Therefore, this study investigated whether FAEEs can be found during a time
      period exceeding 24 hr in a group of patients who were hospitalized for ethanol
      detoxification. A second aim was to study the distribution of FAEEs between
      lipoproteins during that time. METHODS: Serum samples of 12 patients with acute
      ethanol intoxication were assayed for FAEEs. Blood samples were drawn 8.2, 20.2,
      32.2, and 44.2 hr after hospitalization. FAEEs were quantified by gas
      chromatography-mass spectrometry. RESULTS: Ethanol was no longer detectable after
      20.2 hr from hospitalization, whereas FAEEs were still found after 32.2 and 44.2
      hr. These late FAEEs were significantly higher than the FAEEs in 15 different
      healthy men who had abstained from ethanol for 4.5 days (p < 0.001 and p =
      0.001). FAEEs were associated mainly with lipid-free serum but tended to
      accumulate in very-low-density lipoprotein in patients with moderate
      hypertriglyceridemia. CONCLUSIONS: In heavy drinkers, the FAEEs were increased
      after ethanol consumption for at least 44 hr. It remains to be studied whether
      they originate from a single ethanol intake or, in addition, from a slow release
      out of body storage compartments.

PMID- 15252298
TI  - Alcohol reduces GM1 ganglioside content in the serum of inbred mouse strains.
AB  - BACKGROUND: Endogenous and exogenous gangliosides in the plasma affect
      physiologic and pathologic processes such as angiogenesis and atherogenesis.
      However, the genetic and environmental factors that regulate the expression of
      plasma gangliosides are not well known. As shown in the liver and the brain,
      profiles of gangliosides in the plasma may be strain-specific and can be altered
      by intake of alcohol. Therefore, we analyzed serum gangliosides derived from
      inbred mouse strains with and without alcohol treatment. METHODS: C57BL/6ByJ
      (B6By) and BALB/cJ mice (60-70 days old) were injected with 20% alcohol (1-6
      g/kg) or saline intraperitoneally, and the ganglioside content of the serum,
      liver, and cerebellum was measured 4 hr after the injection. Also, the effect of
      oral alcohol self-administration for 18 days with escalating (3-12%)
      concentrations of alcohol on the serum GM1 content was studied in B6By mice. The
      quantification of GM1 was performed with a thin-layer chromatography-staining
      procedure using a cholera toxin B subunit, and the content of other gangliosides
      was measured after staining with resorcinol reagent. RESULTS: We found that basal
      GM1 (containing N-glycolylneuraminic acid) content in the serum of BALB/cJ mice
      (4.8 +/- 0.26 ng/microl) was 25 times higher than that of B6By mice (0.19 +/-
      0.01 ng/microl); the major ganglioside in both strains was GM2. The ganglioside
      profile in the liver was similar to that of the serum, and the GM1 content in
      BALB/cJ was nine times higher than that of B6By. Both injection and oral self
      administration of alcohol lowered GM1 levels in the serum. CONCLUSIONS:
      Endogenous ganglioside profiles in the serum are under genetic control among
      inbred mouse strains, and they can be altered by acute and chronic alcohol
      administration. These genetic and alcohol-induced differences in the plasma
      gangliosides, which appear to reflect ganglioside metabolism in the liver, may
      affect alcohol-related behaviors and pathologic processes.

PMID- 15252299
TI  - Early experience and sex interact to influence limbic-hypothalamic-pituitary
      adrenal-axis function after acute alcohol administration in rhesus macaques
      (Macaca mulatta).
AB  - BACKGROUND: Studies in rodents demonstrate sex differences in neuroendocrine
      stress axis activity after treatment with alcohol. In abstinent alcoholics,
      atypical depressives, and individuals with posttraumatic stress disorder, limbic
      hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among
      females in these patient populations, however, resistance to glucocorticoid
      feedback and increased pituitary reactivity is observed. Early parental loss is a
      major life stressor and is a risk factor for both affective disturbances and LHPA
      axis abnormalities later in life. We wanted to determine whether sex and early
      life parental absence would interact to influence alcohol-induced alterations in
      LHPA-axis activity after exposure to ethanol in macaques. METHODS: Animals were
      reared with their mothers in social groups (MR, n = 94) or without adults in peer
      only groups (PR, n = 79). At 5 years of age, they received an intravenous
      infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing
      condition on ACTH and cortisol levels were analyzed by ANOVA. RESULTS: Peer
      reared females had higher ACTH levels than did PR males, MR females, and MR males
      after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex
      and rearing condition. CONCLUSIONS: These findings suggest that there are sex
      differences in glucocorticoid negative feedback, pituitary responsivity, or
      release of ACTH secretagogues among individuals exposed to early life stress and
      emphasize the importance of considering sex effects when studying LHPA-axis
      dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

PMID- 15252300
TI  - A rat model to determine the biomedical consequences of concurrent ethanol
      ingestion and cigarette smoke exposure.
AB  - BACKGROUND: Although scientists have used animal models for years to study the
      effects of ethanol (EtOH) ingestion on humans, the compounding effect of
      cigarette smoking has been virtually ignored. Because 80 to 95% of human
      alcoholics smoke, it is imperative to consider the added effects of smoking when
      trying to determine the consequences of excessive alcohol ingestion. We therefore
      have developed a rat model for studying the separate and combined results of
      smoking and drinking on human health. METHODS: Male Sprague-Dawley rats were
      exposed daily for 12 weeks in whole-body chambers to cigarette smoke (smoke
      exposed) or room air (sham-exposed). During the final 5 weeks of exposure, the
      rats were fed liquid diets that contained 0, 16, 26, or 36% EtOH calories. Smoke
      exposure was quantified by measurement of carboxyhemoglobin, nicotine, and
      cotinine levels. Body weights, food consumption, blood EtOH concentrations, and
      various assessments of liver damage and function also were followed. RESULTS:
      Smoke exposure in this rat model approximates that of a moderate to heavy human
      smoker. Smoke-exposed rats weighed significantly less and ate less food than sham
      exposed controls, but both groups ingested equivalent amounts of EtOH for their
      body weights and had comparable blood EtOH levels. Liver aspartate and alanine
      aminotransferase levels remained normal. There was an EtOH-induced decrease in
      asialoglycoprotein receptor binding, but it was not exacerbated by smoke
      exposure. Alterations in blood cholesterol levels reflected what has been
      reported for humans, rising with increasing EtOH ingestion and decreasing with
      smoke exposure. CONCLUSION: Our rat model is relevant to what transpires in the
      vast majority of alcoholics. Both ethanol ingestion and smoke exposure can be
      manipulated to mimic light to moderate to heavy levels, making it appropriate for
      studying the separate and combined biomedical consequences of alcohol abuse and
      cigarette smoking.

PMID- 15252301
TI  - Recent advances in cyclic-adenosine monophosphate/protein kinase A signaling in
      ethanol-induced synaptic and behavioral alterations.
AB  - This article represents the proceedings of a symposium at the 2002 RSA Meeting in
      San Francisco, California, organized and co-chaired by L. Judson Chandler and
      Richard A. Morrisett. The presentations were (1) PKA regulates chronic ethanol
      induced synaptic targeting of NMDA receptors, by L. Judson Chandler; (2) Long
      lasting potentiation of GABAergic synapses in dopamine neurons after a single in
      vivo ethanol exposure, by Antonello Bonci; (3) The DARPP-32 cascade and
      regulation of the ethanol sensitivity of NMDA receptors in the nucleus accumbens,
      by Richard A. Morrisett; (4) and The cAMP/PKA signal transduction pathway
      modulates ethanol consumption and sedative effects of ethanol, by Gary S. Wand.

PMID- 15252303
TI  - An illustrated consensus on the classification of pancreatic intraepithelial
      neoplasia and intraductal papillary mucinous neoplasms.
AB  - Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease.
      Several distinct noninvasive precursor lesions can give rise to invasive
      adenocarcinoma of the pancreas, and the prevention, detection, and treatment of
      these noninvasive lesions offers the potential to cure early pancreatic cancers.
      Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include
      pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous
      neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including
      a distinct ovarian-type stroma, and a consistent nomenclature are well
      established for mucinous cystic neoplasms. By contrast, consistent nomenclatures
      and diagnostic criteria have been more difficult to establish for PanINs and
      IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic
      proliferations of columnar, mucin-containing cells with a variable degree of
      papilla formation, the distinction between these two classes of precursor lesions
      remains problematic. Thus, considerable ambiguities still exist in the
      classification of noninvasive neoplasms in the pancreatic ducts. A meeting of
      international experts on precursor lesions of pancreatic cancer was held at The
      Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting
      was to define an international acceptable set of diagnostic criteria for PanINs
      and IPMNs and to address a number of ambiguities that exist in the previously
      reported classification systems for these neoplasms. We present a consensus
      classification of the precursor lesions in the pancreatic ducts, PanINs and
      IPMNs.

PMID- 15252304
TI  - Clusterin expression distinguishes follicular dendritic cell tumors from other
      dendritic cell neoplasms: report of a novel follicular dendritic cell marker and
      clinicopathologic data on 12 additional follicular dendritic cell tumors and 6
      additional interdigitating dendritic cell tumors.
AB  - While tumors of dendritic cell lineage may have overlapping histomorphologic
      features, most but not all cases can be classified using an immunohistochemical
      panel, including CD21, CD23, CD35, CD1a, and S-100. Based on observations that
      clusterin is expressed in benign follicular dendritic cells, clusterin expression
      in 32 dendritic cell tumors was evaluated. Diffuse strong staining for clusterin
      was seen in 12 of 12 follicular dendritic cell tumors. Two of these cases were
      negative for traditional markers (CD21, CD23, CD35); they were classified based
      on characteristic ultrastructural features. Three of 6 interdigitating dendritic
      cell tumors were negative for clusterin and 3 showed focal weak positivity.
      Clusterin staining in Langerhans cell histiocytosis ranged from negative (6 of
      14) to weak/moderate (8 of 14). Follicular dendritic cell tumors behaved as
      benign tumors or low-grade sarcomas. Interdigitating dendritic cell tumors
      demonstrated a widely variable behavior, ranging from benign to rapidly fatal
      disease. Based on this initial study, strong clusterin staining supports a
      diagnosis of follicular dendritic cell tumor. Thus, staining for clusterin is
      useful in classification of dendritic cell tumors, particularly when the more
      common markers of follicular dendritic cells are not expressed.

PMID- 15252305
TI  - Histologic predictors of pouchitis in patients with chronic ulcerative colitis.
AB  - Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in
      ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal
      anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters
      have been evaluated, reliable pathologic predictors for the development of
      pouchitis are lacking. The purpose of this case-control study was to determine
      whether there are any pathologic features in UC colectomy specimens that may help
      predict the subsequent development of pouchitis after an IPAA procedure. The
      study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35
      years), who had at least 1 episode of pouchitis after an IPAA procedure during
      the follow-up period (mean: 57 months, range: 12-121 months). There were 26
      control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also
      underwent a total colectomy and IPAA procedure for UC, but did not develop
      pouchitis during the follow-up period (mean: 78 months, range: 14-223 months).
      Routinely processed tissues from each colectomy specimen were evaluated for a
      variety of histologic features, such as extent of colitis, severity of colitis,
      extent of severe colitis, type and extent of ulceration, presence and severity of
      appendiceal inflammation, and the presence of active ileitis, and compared
      between the study and control patients. Pathologic features that were associated
      with the subsequent development of pouchitis included the presence of severe
      colitis that extended into the cecum (severe pancolitis), which was present in
      7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P =
      0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%)
      controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis
      patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration
      [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No
      significant differences in patient gender or age, depth or extent of ulceration,
      or the presence or absence of "backwash ileitis" were identified between the 2
      groups. In conclusion, there are several histologic features in colectomy
      specimens from UC patients who have undergone an IPAA procedure that may help
      predict the subsequent development of pouchitis. Of these features, appendiceal
      ulceration is highly associated with pouchitis.

PMID- 15252306
TI  - Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression
      of lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal
      smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs.
      We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a
      new specific marker for lymphatic endothelial cells, as well as the expression of
      vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from
      6 autopsy cases, a single lung transplant case, and 8 surgical cases for
      analyses. We demonstrated that lymphatics were extremely abundant in both
      pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only
      proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and
      that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium
      surrounding the area where LAM cells proliferate. In contrast, angiogenesis,
      confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells
      demonstrated positive reactivity against anti-VEGF-C antibody at varying
      intensities. Significant correlation (P < 0.001) was noted between the degree of
      lymphangiogenesis in LAM or VEGF-C expression on LAM cells and
      lymphagioleiomyomatosis histologic score (LHS), which represents the histologic
      severity of pulmonary LAM and has been reported to have prognostic significance.
      Our study is likely to provide a novel point of view on the pathophysiologic
      significance of lymphangiogenesis in LAM.

PMID- 15252307
TI  - Proliferative nodules in congenital melanocytic nevi: a clinicopathologic and
      immunohistochemical analysis.
AB  - Congenital melanocytic nevi (CMN) occur in 1% to 2% of newborns, and the risk of
      malignant melanoma is increased in patients with large CMN. Appearance at birth
      or later of a nodular or hyperpigmented area within a CMN simulates malignant
      melanoma and prompts biopsy. Although their clinical and pathologic features seem
      ominous, proliferative nodules (PNs) typically are benign and may regress,
      although atypical features cause greater concern. Here we report clinical and
      pathologic findings with outcome in 10 children who had multiple biopsies of
      large CMN with PNs. We reviewed 78 separate samples from the 10 patients and
      classified the 60 PNs according to published criteria. A subset of 30 samples
      containing both the CMN and a PNs was analyzed for immunohistochemical reactivity
      for melanocytic (S-100 protein, HMB45, melan-A), lymphocytic (CD45), cell
      cycle/proliferative (Mib-1, p16, p21, p27, c-Myc), apoptotic (p53, Bax, c-kit,
      CD95), and anti-apoptotic (bcl-2) markers. Both CMN and PNs had similar
      expression of melanocytic, lymphocytic, and most cell-cycle/proliferative and
      apoptotic markers, including Mib-1, p16, p21, p27, c-Myc, Bax, CD95, and bcl-2. A
      greater proportion of PNs than CMN were reactive for p53 (67% vs. 30%, P <
      0.0098) and c-kit (97% vs. 3%, P < 0.0001). p53 and p21 expression in CMN and all
      types of PNs were inversely correlated. When ordinary and atypical PNs were
      compared, the atypical PNs more frequently expressed p53, Mib-1, Bax, and bcl-2,
      but less frequently expressed p21. The c-kit expression in nearly all PNs and its
      absence in nearly all CMN is potentially useful for recognition of PN, suggests a
      delayed melanocytic maturation process in proliferative nodules, and may be
      likely indicative of their benign nature. p53 reactivity in concert with a lack
      of p21 up-regulation by immunohistochemistry suggests that a p53 mutation may be
      present in PN, although the immunohistochemical findings alone cannot exclude
      possible overexpression of wild-type p53. Regressive, involutional, or
      maturational changes were observed in sequential samples from 4 patients. No
      patient developed malignant melanoma or another melanocytic nevus-associated
      malignancy during the follow-up period. These findings underscore the
      similarities between PNs and the underlying CMN and suggest that maturational,
      proliferative, and apoptotic processes are involved in their clinical evolution.

PMID- 15252308
TI  - Immunophenotypic differences between intestinal-type and low-grade papillary
      sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing
      CDX2 and MUC2.
AB  - Nonsalivary sinonasal adenocarcinomas can be divided into low-grade and high
      grade tumors. The former are often papillary and the latter are usually of
      intestinal type, morphologically similar to metastatic colonic carcinoma.
      Antibodies to CDX2, a transcription factor gene highly specific for intestinal
      adenocarcinomas, MUC2, a mucin gene expressed in adenocarcinomas from various
      sites, and cytokeratins (CK) 7 and 20 were used to examine the two groups of
      tumors. Formalin-fixed, paraffin-embedded tissue from 22 sinonasal
      adenocarcinomas was reclassified into 9 high-grade intestinal-type, 3 high-grade
      nonintestinal, and 10 low-grade, predominantly papillary adenocarcinomas.
      Immunohistochemical staining was graded on a 0 to 4+ scale with 5% or greater
      tumor cell staining considered positive. Of the high-grade intestinal group, 78%
      demonstrated 4+ CDX2 positivity, with 44% MUC2 positive. Although 89% of this
      group was CK7 positive, the percent of staining was variable. A majority (67%) of
      the intestinal cases was 4+ CK20 positive. Almost every nonintestinal
      adenocarcinoma (90%) (low- and high-grade) was CK7 positive (7 of 9, 4+), without
      expression of any of the three colonic adenocarcinoma markers. The three high
      grade nonintestinal tumors had the expression profile of the low-grade papillary
      group with the exception of focal MUC2 positivity in 1 case. Intestinal-type
      adenocarcinomas have an expression profile distinct from nonintestinal sinonasal
      adenocarcinomas. The former are similar, but not identical, to colonic
      adenocarcinomas. Immunohistochemical staining for CDX2, MUC2, and differential
      cytokeratins does not differentiate metastatic colorectal from primary sinonasal
      intestinal-type adenocarcinoma.

PMID- 15252309
TI  - Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and
      bizarre parosteal osteochondromatous proliferation (Nora lesion).
AB  - BACKGROUND: Proliferative lesions of the bone surface, such as subungual
      (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation
      (BPOP, Nora lesion) are currently classified as reactive, proliferative processes
      that mimic primary neoplasms of bone. METHODS: Cytogenetic analysis was performed
      on 3 subungual exostoses of the great toe and 2 BPOP lesions of the radius and
      ulna. RESULTS: A balanced translocation t(X;6) was identified in all cases of
      subungual exostoses. The chromosomal rearrangements observed in 1 case of BPOP
      differed from those seen in subungual exostosis. CONCLUSIONS: The presence of
      chromosomal abnormalities in subungual exostosis and BPOP suggests that these
      lesions are neoplastic, with a different molecular pathogenesis, and that each is
      a distinct clinicopathologic entity.

PMID- 15252310
TI  - Low-grade salivary duct carcinoma: description of 16 cases.
AB  - Low-grade salivary duct carcinoma is a rare neoplasm. We report on 16 patients,
      with a median age of 64 years. All but one tumor arose from the parotid gland,
      including one tumor that arose in an intraparotid lymph node; one arose in the
      submandibular gland. Tumors consist of single to multiple dominant cysts,
      accompanied by adjacent intraductal proliferation. Cysts are lined by small,
      multilayered, proliferating, bland ductal cells with finely dispersed chromatin
      and small nucleoli. Separate, smaller ductal structures are variably filled by
      proliferating ductal epithelium with cribriform, micropapillary, and solid areas.
      The overall appearance is very similar to breast atypical ductal hyperplasia and
      low-grade ductal carcinoma in situ. Foci of definitive stromal invasion were seen
      in four tumors. Two tumors demonstrated transition from low- to intermediate- or
      high-grade cytology, with scattered mitotic figures and focal necrosis. S-100
      revealed diffuse strong expression in all 9 cases studied. Myoepithelial markers
      (calponin) highlighted supportive myoepithelial cells rimming the cystic spaces,
      confirming the intraductal nature of most, or all, of six tumors studied. Nine
      tumors studied for Her2-neu antigen were uniformly negative. Follow-up was
      obtained on 13 of our 16 patients. All patients were disease-free after surgery 6
      to 132 months (median 30 months). Low-grade salivary duct carcinoma is a low
      grade neoplasm with an excellent prognosis; it may be treated by conservative but
      complete resection. Its resemblance to atypical breast ductal hyperplasia, or
      micropapillary/cribriform intraductal carcinoma, distinguishes it from high-grade
      salivary duct carcinoma, papillocystic acinic cell carcinoma, and
      cystadenocarcinoma.

PMID- 15252311
TI  - Expression of RON Proto-oncogene in Renal Oncocytoma and Chromophobe Renal Cell
      Carcinoma.
AB  - Recently, it was reported that RON proto-oncogene, encoding a receptor tyrosine
      kinase, was strongly expressed in renal oncocytomas but not in any renal cell
      carcinomas, including 5 chromophobe renal cell carcinomas, which morphologically
      resemble oncocytomas. To determine its diagnostic value, we studied Ron protein
      expression by immunohistochemistry in a larger number of renal cell neoplasms
      with emphasis on chromophobe renal cell carcinomas. Tissue microarrays containing
      141 renal cell neoplasms, including 55 oncocytomas and 52 chromophobe renal cell
      carcinomas, were constructed. In addition, conventional sections from 15 cases of
      oncocytoma and 5 cases of chromophobe renal cell carcinoma were analyzed.
      Immunohistochemistry was carried out with a monoclonal mouse anti-human Ron-alpha
      antibody. Staining intensity was scored on a 0 to 3 scale. Ninety-nine percent of
      oncocytomas (69 of 70) and 96% of chromophobe renal cell carcinomas (55 of 57)
      showed moderate to strong, diffuse cytoplasmic Ron immunoreactivity with
      intensities > or =2, while only 17% of other renal cell carcinoma subtypes
      stained with intensities > or =2. Our study indicates that Ron immunostaining
      cannot be used to distinguish oncocytoma from chromophobe renal cell carcinoma.

PMID- 15252312
TI  - Aberrant Bcl6 protein expression in mantle cell lymphoma.
AB  - Mantle cell lymphoma is routinely considered as a Bcl6-negative B-cell lymphoma
      carrying the translocation t(11;14). Here we describe a series of five Bcl6
      positive mantle cell lymphoma cases, including three classic and two blastoid
      variants. The proliferative index of these cases, measured with the Ki-67
      antibody, was slightly higher than in Bcl6-negative mantle cell lymphoma cases
      (32.2 vs. 23.7%) Bcl6 expression was associated with translocations involving
      3q27 in four of the five cases and an extra copy of the BCL6 gene in the fifth. A
      mutational study of the major mutational cluster in the BCL6 gene revealed no
      increased mutation rate, except in one case. One of the three cases displayed a
      high mutational index in the IgVH gene, suggesting exposure to a germinal center
      microenvironment. Chromosomal alterations involving 3q27 seem to be responsible
      for this increased Bcl6 expression, which needs to be considered when Bcl6 is
      used in lymphoma diagnosis.

PMID- 15252313
TI  - A diagnostically useful histopathologic feature of endometrial polyp: the long
      axis of endometrial glands arranged parallel to surface epithelium.
AB  - We describe a histologic feature useful in the diagnosis of endometrial polyps,
      namely, the parallel arrangement of the endometrial glands' long axis to the
      surface epithelium (PGE). Polyps that are removed intact are usually easy to
      diagnose because of the polypoid appearance plus surface epithelium on all sides.
      In addition, there are thick-walled blood vessels and irregularly shaped glands.
      Rarely are all or even some of the characteristic features easy to identify in
      biopsies and curettage specimens. We evaluated 76 cases of grossly identifiable
      polyps from hysterectomy or polypectomy (working group) for various histologic
      features and tested the validity of those findings with another 75 specimens
      (test group), which had been diagnosed as polyps in another institute by separate
      investigators. The frequency of the various histologic features in the polyps
      varied depending on the menstrual state, shape, and histologic types of the
      polyps. PGE was found in 80% (40 of 50 polyps) of premenopausal women as the most
      common histologic feature, but it was less common in postmenopausal women (42%,
      11 of 26) (P = 0.001). All functional polyps (100%, 19 of 19), many of
      hyperplastic polyp (65%, 20 of 31), and some fibrous polyps (38%, 8 of 21) showed
      the change. In premenopausal women, incidence of PGE was significantly different
      by the polyp's shape or histologic types (P < 0.05), but not in postmenopausal
      women. PGE was not identified in any of the 56 normal background endometria, even
      though the surface was often undulated. Almost identical findings were observed
      in the series from the test group, confirming the validity of this new finding.
      In summary, PGE, if present, is a useful histologic finding in facilitating the
      diagnosis of endometrial polyp in curettage specimens.

PMID- 15252314
TI  - Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans.
AB  - Using gene microarray expression profiling, we previously found that
      apolipoprotein D (Apo D) was highly expressed in dermatofibrosarcoma protuberans
      (DFSP). In this study, we confirm that Apo D is highly and relatively
      specifically expressed in DFSP using immunohistochemistry. A tissue microarray
      containing 421 soft tissue tumors was constructed and stained with antibodies
      against Apo D and CD34. Cytoplasmic immunostaining for Apo D was found in 9 of 10
      typical DFSPs. In addition, 3 of 3 Bednar tumors and 2 of 3 giant cell
      fibroblastomas stained in conventional sections. In contrast, Apo D was
      immunoreactive in only a very small subset of a diverse collection of other soft
      tissue tumors, including Malignant Fibrous Histiocytoma (MFH), glomus tumor,
      neurofibroma, and malignant peripheral nerve sheath tumors. Immunostains for Apo
      D were negative in conventional sections of 16 fibrous histiocytomas, and an
      additional 12 variants of fibrous histiocytoma. Digital images of all
      immunohistochemical and hematoxylin and eosin tissue microarray stains are
      available at the accompanying website (http://microarray
      pubs.stanford.edu/tma_portal/apod/). We conclude that Apo D is strongly expressed
      in DFSPs and neural lesions and may be useful in differentiating DFSP from
      fibrous histiocytoma.

PMID- 15252315
TI  - Cylindroma of the breast of skin adnexal type: a study of 4 cases.
AB  - Four cases of solitary cylindroma of the breast of skin adnexal type are
      described. The tumors were morphologically and immunophenotypically identical to
      their dermal counterparts. They arose in close proximity to the nipple, such as
      the retroareolar area of the breast and in intimate association with the
      lactiferous ducts, suggesting an origin from the latter structures. One case
      occurred in a woman with hereditary multiple cylindromatosis (Brooke-Spiegler
      syndrome). This is the second reported case of this hereditary syndrome with
      extracutaneous manifestations and the first case in which the breast is involved.

PMID- 15252316
TI  - Current practical applications of diagnostic immunohistochemistry in breast
      pathology.
AB  - In recent years, immunohistochemistry has assumed an increasingly prominent role
      in diagnostic breast pathology. Immunohistochemistry is now frequently used in
      the evaluation of many epithelial proliferations of the breast. Common
      applications include the use of myoepithelial markers to evaluate for stromal
      invasion, E-cadherin to distinguish between ductal and lobular neoplasia, high
      molecular weight cytokeratins to differentiate usual ductal hyperplasia from
      ductal carcinoma in situ, immunohistochemical profiles to characterize site of
      origin of metastatic carcinomas, and cytokeratin stains to detect metastases in
      sentinel lymph nodes. Recent advances, practical considerations, and potential
      pitfalls in the use of immunohistochemistry in these five diagnostic categories
      are discussed herein.

PMID- 15252317
TI  - Error in surgical pathology.
AB  - A total of 272 surgical pathology claims reported to The Doctors Company from
      1998 through 2003 were reviewed. They were analyzed and repetitive patterns
      involving both specimen type and category of diagnostic error were identified.
      These patterns were then compared with those uncovered in a prior review of 218
      surgical pathology claims reported from 1995 through 1997 to identify trends and
      see if new patterns of diagnostic error had emerged.

PMID- 15252318
TI  - Tribute to Kamal G. Ishak, MD, PhD.

PMID- 15252319
TI  - Metastatic juxtaglomerular cell tumor in a 52-year-old man.
AB  - Juxtaglomerular cell tumor is a rare renal neoplasm arising from the
      juxtaglomerular apparatus. Approximately 70 cases have been reported in the
      English literature since it was first described by Robertson et al in 1967. This
      tumor has been considered benign and resection has so far been curative. In this
      paper, we report the first metastatic juxtaglomerular cell tumor. The 15-cm tumor
      occurred in the right kidney of a 46-year-old man. It invaded the renal vein, and
      was treated by radical nephrectomy in 1995. The diagnosis at that time was renal
      cell carcinoma. The patient was well for 6 years and then developed bilateral
      lung masses, which were resected. Microscopically, the tumors from the kidney and
      the lungs were similar, consisting of solid sheets of uniformly round-to
      polygonal cells intermixed with abundant delicate vasculature. Both renal and
      pulmonary tumors were positive for vimentin, renin, and only focally to CD34.
      Electron microscopic studies performed on the paraffin-embedded renal tumor and
      formalin-fixed lung tumor revealed the typical rhomboid crystals of proto-renin.
      In consideration of the characteristic morphologic features,
      immunohistochemistry, and the presence of rhomboid crystals of proto-renin, the
      diagnosis was modified to malignant juxtaglomerular cell tumor.

PMID- 15252320
TI  - An unusual composite endometrial tumor combining papillary serous carcinoma and
      small cell carcinoma.
AB  - This is the first report in the English literature of a composite endometrial
      tumor composed of papillary serous carcinoma and small cell carcinoma. A 79-year
      old woman underwent total abdominal hysterectomy and left salpingo-oophorectomy
      due to endometrial carcinoma. Grossly, the uterus was enlarged with an irregular
      and nodular serosal surface, thickened myometrium, and irregular endometrium.
      Microscopic examination revealed an endometrial carcinoma composed of papillary
      serous carcinoma and small cell carcinoma. There was a differential
      immunoreactivity between the two components: the cells of the papillary serous
      carcinoma were positive for cytokeratin, CA-125, CEA, and HER-2/Neu, whereas
      these markers were negative in the small cell carcinoma. Various neuroendocrine
      markers were positive in the small cell carcinoma and negative in the papillary
      serous carcinoma. Fluorescence in situ hybridization analysis using 4, 8, and 10
      centromeric probes revealed hyperploidy (6-8 signals) in the small cell carcinoma
      cells. Most of the serous carcinoma cells were euploid, with scattered trisomies
      and tetrasomies of these chromosomes. The patient died of progressive disease 5
      months after surgery. We suggest that the small cell carcinoma may have arisen
      from the endometrial papillary serous carcinoma undergoing tumor progression with
      neuroendocrine differentiation.

PMID- 15252321
TI  - Perivascular epithelioid clear cell tumor of the common bile duct.
AB  - The perivascular epithelioid clear cell tumor (PEComa) has been described in a
      number of locations, including the pancreas, uterus, bladder, prostate, and
      gastrointestinal tract. We report the existence of a similar tumor occurring in
      the distal common bile duct of a 51-year-old man admitted for obstructive
      jaundice. The tumor had characteristic histologic features of a PEComa, including
      a richly vascular organoid architecture, tumor cells with clear to lightly
      eosinophilic cytoplasm, and variably prominent nucleoli. Immunohistochemically,
      the tumor cells were positive for HMB-45 and neuron specific enolase but negative
      for epithelial markers, smooth muscle markers, other neuroendocrine markers,
      vimentin, melan-A, and S-100 protein. PEComas appear to be ubiquitous tumors with
      characteristic histology and immunophenotype. Although most of these tumors have
      behaved in a benign fashion, they should be considered tumors of uncertain
      malignant potential given previous reports of recurrence and metastases. During a
      short follow-up period following a conservative local excision, our patient
      remains free of disease.

PMID- 15252322
TI  - Signet-ring cell change in pseudomembranous colitis versus signet-ring cell
      carcinoma.

PMID- 15252323
TI  - Signet-ring cell change in acute erosive gastropathy.

PMID- 15252324
TI  - Follow-up of in situ and early-stage fallopian tube carcinoma in patients
      undergoing prophylactic surgery for proven or suspected BRCA-1 or BRCA-2
      mutations.

PMID- 15252325
TI  - Lymphoplasmacytic sclerosing pancreatitis is a pancreatic lesion of IgG4-related
      systemic disease.

PMID- 15252326
TI  - Pigmented epithelioid melanocytoma.

PMID- 15252345
TI  - Validity and reliability of the revised convergence insufficiency symptom survey
      in children aged 9 to 18 years.

PMID- 15252347
TI  - Idiopathic polypoidal choroidal vasculopathy (IPCV) presenting with simultaneous
      choroidal neovascular membrane (CNM).
AB  - Idiopathic polypoidal choroidal vasculopathy (IPCV), a rare retinal condition
      initially described in 1982, is characterized by retinal pigment epithelial (RPE)
      detachments associated with choroidal polypoidals. Although it is recognized as a
      unique entity, many consider it a peculiar representation of choroidal
      neovascular membrane (CNM), commonly associated with age-related macular
      degeneration (ARMD). We report a case of IPCV with simultaneous presentation of
      CNM. Dilated examination and fluorescein angiography (FA) revealed RPE
      detachments associated with choroidal polypoidals. FA also revealed a lacy
      hyperfluorescent vascular lesion. Ocular manifestations, differential diagnoses,
      and treatment options are discussed, with emphasis on similarities and
      differences between IPCV and CNM. It is imperative to consider IPCV in the
      differential diagnosis of RPE detachments, including those associated with CNM.
      Careful funduscopic evaluation, FA, and/or indocyanine green videoangiography
      analysis helps confirm the diagnosis.

PMID- 15252348
TI  - Late-onset blebitis/endophthalmitis: incidence and outcomes with mitomycin C.
AB  - PURPOSE: To assess the outcomes of patients who had late infections after
      undergoing filtering surgery with mitomycin C with respect to treatment,
      resultant vision, and maintenance of intraocular pressure. METHODS: A
      retrospective review of 233 eyes that underwent trabeculectomy with mitomycin C
      with or without coincident cataract extraction and intraocular lens insertion
      from August 1993 to June 1997 was undertaken. Records were examined for
      postoperative infection occurring at least 6 months after filtering surgery. Age,
      sex, date, and type of surgery were reviewed and entered into a computerized
      database. RESULTS: Bleb infections occurred in 6 of 233 (2.6%) eyes that
      underwent mitomycin C filtering surgery. Four of these developed endophthalmitis.
      The average postoperative time until infection was 24.7 months. Two patients had
      bleb leaks, one of which progressed to endophthalmitis. On resolution of
      infection, all blebs remained functional, and vision returned to preblebitis
      acuities in 67%. CONCLUSION: Aggressive topical antibiotic therapy with daily
      observation may be appropriate in selected cases of late-onset blebitis and
      endophthalmitis. Eyes may continue to have good visual outcomes and functioning
      filters without need for additional surgery or hospitalization. Early recognition
      and appropriate management of infections may play a role in these outcomes.

PMID- 15252349
TI  - Minimal angle horizontal strabismus detectable by lay observers.
AB  - PURPOSE: Patients with socially significant strabismus may be at risk for certain
      psychosocial consequences. However, the magnitude at which strabismus becomes
      socially significant is ill defined. Suggested criteria for socially significant
      strabismus can be found in the literature, but they are rarely, if ever,
      referenced. The purpose of this study is to further define the magnitude at which
      strabismus becomes socially significant according to lay observers. METHODS:
      Strabismus was simulated using photo manipulation and off-center fixation.
      Horizontal deviations were created in 3Delta steps up to 24Delta. One model was
      used for all photos. The photos were presented in random order to non-health care
      professionals (N = 58). Participants were instructed to view each picture and
      determine: "yes, this person has an eye turn" or "no, this person does not have
      an eye turn." A chi test was used for analysis. RESULTS.: There was an increase
      in the likelihood of strabismus detection as the size of the angle increased for
      exotropia and esotropia. Overall, exotropia was easier to identify than
      esotropia. For esotropia, a dramatic increase in detectability occurred between
      9Delta (47.41% detection; p = 0.001) and 12Delta (67.24% detection; p = 0.001),
      with 70% detection being achieved at 14.5Delta. A significant increase in
      detection of exotropia occurred between 6Delta (60.34% detection; p = 0.001) and
      9Delta (77.59% detection; p = 0.001), with 70% detection achieved at 8Delta.
      CONCLUSIONS: Our results suggest that exotropia is easier for lay observers to
      detect than esotropia, with the critical magnitude (70% detection) being
      14.5Delta for esotropia and 8Delta for exotropia. This refutes generally accepted
      beliefs that esotropia is easier to detect than exotropia. Additional studies are
      needed to look at the effect of ethnicity, sex, and age. Multiple models should
      be used to reduce the possible influence of distinct facial characteristics and
      increase the generalizability of the results.

PMID- 15252350
TI  - Long-term changes in visual acuity and refractive error in amblyopes.
AB  - PURPOSE: To report long-term changes in visual acuity and refractive error for
      strabismic, anisometropic, and isoametropic amblyopes. METHODS: Records of
      patients with strabismic amblyopia, anisometropic amblyopia, and isoametropic
      amblyopia who were treated from 1983 to 1993 were reviewed. Excluded were
      patients having ocular or neurological diseases, developmental delay, and follow
      up <4 years after treatment cessation. Data included best-correctable visual
      acuity and spherical equivalent refractive error of the amblyopic and the
      nonamblyopic eye at pretreatment, posttreatment, and long-term follow-up.
      RESULTS: Records for 61 patients met the inclusion criteria. For strabismic
      amblyopia (n = 22), mean visual acuity in amblyopic and nonamblyopic eyes
      improved 0.36 and 0.05 logarithm of the minimum angle of resolution (logMAR)
      units after a mean treatment time of 1 year. At long-term follow-up (mean = 9.3
      years after treatment), visual acuity in the amblyopic eye regressed 0.09 logMAR
      and visual acuity in the nonamblyopic eye improved 0.10 logMAR units. For
      anisometropic amblyopia (n = 26), mean visual acuity in amblyopic and
      nonamblyopic eyes improved 0.30 and 0.02 logMAR units, respectively, after a mean
      treatment period of 1.1 year. At the long-term follow-up visit (mean = 7.1 years
      after treatment), visual acuity in the amblyopic eye regressed 0.09 logMAR unit
      and in the nonamblyopic eye improved 0.03 logMAR unit. Repeated-measures analysis
      of variance showed no significant effect of type of amblyopia on visual acuity of
      the amblyopic eye and a significant effect of visit due to treatment but not
      regression. The changes in visual acuity in the nonamblyopic eye from the
      pretreatment to the follow-up visit were significant and interacted with type,
      the changes being larger in strabismic amblyopia. For strabismic amblyopia, the
      mean refractive error in amblyopic and nonamblyopic eyes changed from +2.15 D and
      +1.85 D, respectively, initially to +0.45 D and +0.58 D, respectively, at the
      follow-up visit. For anisometropic amblyopia, the mean refractive error in
      amblyopic and nonamblyopic eyes changed from +1.04 D and +0.12 D, respectively,
      initially to +0.23 D and -0.94 D, respectively, at the follow-up visit. The
      effect of visit on amblyopic and nonamblyopic refractive errors was significant.
      For isoametropic amblyopia (n = 13), visual acuity in both right and left eyes
      initially was 0.39 logMAR unit and improved to 0.14 logMAR unit in each eye after
      a mean follow-up of 8.9 years. Refractive error in the right and the left eyes
      changed from -1.22 D and -1.14 D, respectively, to -2.68 D and -2.56 D,
      respectively, at follow-up. These differences were all significant. CONCLUSIONS:
      After treatment and with long-term follow up, visual acuity regresses but not
      significantly in the amblyopic eye in strabismic amblyopia and anisometropic
      amblyopia. At the same time, visual acuity in the nonamblyopic eye improves
      slightly. Visual acuity also improves significantly over time in isoametropic
      amblyopia. The refractive error of both amblyopic and nonamblyopic eyes tends to
      show a myopic shift regardless of the type of amblyopia.

PMID- 15252351
TI  - Using the Freiburg Acuity and Contrast Test to measure visual performance in USAF
      personnel after PRK.
AB  - PURPOSE: Photorefractive keratectomy (PRK) may be an alternative to spectacle and
      contact lens wear for United States Air Force (USAF) aircrew and may offer some
      distinct advantages in operational situations. However, any residual corneal haze
      or scar formation from PRK could exacerbate the disabling effects of a bright
      glare source on a complex visual task. The USAF recently completed a longitudinal
      clinical evaluation of the long-term effects of PRK on visual performance,
      including the experiment described herein. METHODS: After baseline data were
      collected, 20 nonflying active duty USAF personnel underwent PRK. Visual
      performance was then measured at 6, 12, and 24 months after PRK. Visual acuity
      (VA) and contrast sensitivity (CS) data were collected by using the Freiburg
      Acuity and Contrast Test (FrACT), with the subject viewing half of the runs
      through a polycarbonate windscreen. Experimental runs were completed under 3
      glare conditions: no glare source and with either a broadband or a green laser
      (532-nm) glare annulus (luminance approximately 6090 cd/m) surrounding the
      Landolt C stimulus. RESULTS: Systematic effects of PRK on VA relative to baseline
      were not identified. However, VA was almost 2 full Snellen lines worse with the
      laser glare source in place versus the broadband glare source. A significant drop
      off was observed in CS performance after PRK under conditions of no glare and
      broadband glare; this was the case both with and without the windscreen. As with
      VA, laser glare disrupted CS performance significantly and more than broadband
      glare did. CONCLUSIONS: PRK does not appear to have affected VA, but the changes
      in CS might represent a true decline in visual performance. The greater
      disruptive effects from laser versus broadband glare may be a result of increased
      masking from coherent spatial noise (speckle) surrounding the laser stimulus.

PMID- 15252352
TI  - Reading speed benefits from increased vertical word spacing in normal peripheral
      vision.
AB  - PURPOSE: Crowding, the adverse spatial interaction due to proximity of adjacent
      targets, has been suggested as an explanation for slow reading in peripheral
      vision. The purposes of this study were to (1) demonstrate that crowding exists
      at the word level and (2) examine whether or not reading speed in central and
      peripheral vision can be enhanced with increased vertical word spacing. METHODS:
      Five normal observers read aloud sequences of six unrelated four-letter words
      presented on a computer monitor, one word at a time, using rapid serial visual
      presentation (RSVP). Reading speeds were calculated based on the RSVP exposure
      durations yielding 80% correct. Testing was conducted at the fovea and at 5
      degrees and 10 degrees in the inferior visual field. Critical print size (CPS)
      for each observer and at each eccentricity was first determined by measuring
      reading speeds for four print sizes using unflanked words. We then presented
      words at 0.8x or 1.4x CPS, with each target word flanked by two other words, one
      above and one below the target word. Reading speeds were determined for vertical
      word spacings (baseline-to-baseline separation between two vertically separated
      words) ranging from 0.8x to 2x the standard single-spacing, as well as the
      unflanked condition. RESULTS: At the fovea, reading speed increased with vertical
      word spacing up to about 1.2x to 1.5x the standard spacing and remained constant
      and similar to the unflanked reading speed at larger vertical word spacings. In
      the periphery, reading speed also increased with vertical word spacing, but it
      remained below the unflanked reading speed for all spacings tested. At 2x the
      standard spacing, peripheral reading speed was still about 25% lower than the
      unflanked reading speed for both eccentricities and print sizes. Results from a
      control experiment showed that the greater reliance of peripheral reading speed
      on vertical word spacing was also found in the right visual field. CONCLUSIONS:
      Increased vertical word spacing, which presumably decreases the adverse effect of
      crowding between adjacent lines of text, benefits reading speed. This benefit is
      greater in peripheral than central vision.

PMID- 15252353
TI  - Corneal and lenticular components of total astigmatism in a preschool sample.
AB  - PURPOSE: To examine the contribution of corneal and lenticular components to
      total astigmatism in preschool low and high astigmats to determine whether there
      was any compensation for high astigmatism by the lenticular component. METHODS:
      Cycloplegic refractive and keratometric measures using the Retinomax K-Plus
      (Nikon Inc., Melville, NY) were conducted on 129 children (mean age, 51.1 +/- 8.4
      mo) in Oxford County, Canada. We divided the sample into high astigmats (total
      cylinder > or =1 D; mean, 1.38 +/- 0.43 D; n = 29) and normal astigmats (total
      cylinder < or =0.75 D; mean, 0.22 +/- 0.20 D; n = 100). Measures of total and
      corneal cylinder were transposed into J0 and J45 components, where positive and
      negative J0 values quantified with-the-rule (WTR) and against-the-rule
      astigmatisms, respectively, and J45 quantified oblique astigmatism. RESULTS: WTR
      astigmatism was dominant in both the high and normal astigmatic group. J0 and J45
      components of corneal astigmatism were highly correlated with total astigmatism
      in high astigmats, whereas only J0 was significantly correlated with total
      astigmatism in normal astigmats. Although the magnitude of total and corneal
      cylinder was significantly greater in high astigmats, overall lenticular cylinder
      was similar in both groups. However, the Fourier transforms showed high astigmats
      to have significantly lower lenticular J0 and higher lenticular J45 than the
      normal astigmats. CONCLUSIONS: Astigmatism in 3- to 5-year-old children is
      primarily corneal. In preschool children, the lens does not vary in response to
      high amounts of corneal WTR astigmatism, and in fact, it increases the oblique
      astigmatism component when the corneal component is high. In high astigmats,
      lenticular astigmatism contributes to both J0 and J45 components, whereas the
      corneal contribution is primarily J0.

PMID- 15252354
TI  - Blur adaptation and myopia.
AB  - Previous studies have demonstrated a significant improvement in visual resolution
      during sustained periods of retinal defocus. This appears to result from
      perceptual adaptation designed to restore the perceived contrast of the degraded
      image. However, it is unclear whether perceptual adaptation to sustained blur is
      present in all individuals or only in certain subgroups, such as those who have
      been chronically exposed to sustained periods of blur due to uncorrected
      ametropia. Accordingly, the present study examined the effects of sustained
      retinal defocus on both high-and low-contrast visual acuity in emmetropes (n =
      13) and myopes (n = 18). Subjects were required to view through +2.50-D spherical
      lenses worn over their distance refractive correction for a continuous 2-hour
      period. A significant improvement in both Landolt C and grating visual acuity
      measured through the fogging lenses was observed in both refractive groups.
      Although the mean change in grating visual acuity was significantly greater for
      the myopic subjects, the improvements in Landolt C acuity observed in the
      emmetropes and myopes were statistically equivalent. We hypothesize that the
      improvement in visual acuity results from perceptual adaptation to the blurred
      images, which may occur at central sites within the visual cortex.

PMID- 15252355
TI  - Vision health care providers' attitudes and experiences with preschool vision
      screening in Ontario.
AB  - PURPOSE: The validity of preschool vision screening has been questioned in the
      light of the World Health Organization's criteria for determining the validity of
      screening programs. However, recommendations toward preschool screening have been
      made by a number of organizations. Given the contrasting views of screening, the
      purpose of this study was to examine visual health care provider experiences and
      attitudes toward preschool screening. METHOD: Optometrists, public health
      administrators, pediatric ophthalmologists, and orthoptists were surveyed about
      opinions of, recommendations for, and experiences with preschool vision screening
      in Ontario. The survey focused on four areas, including general opinion of
      preschool screening, screening standards and practices, provider experience with
      preschool screening, and barriers to preschool screening. In addition, survey
      responses were broken down by regional access to health care. RESULTS: Overall,
      strong support for preschool vision screening and movement toward standardization
      of screening practice was found among all surveyed groups. Although support for
      vision screening in low health care access areas was strong, providers estimated
      that parent compliance to screening was weaker in low access areas. Providers
      also reported considerable variability in vision screening practices. In
      addition, although the majority of providers had been involved in a screening
      program, the majority was no longer involved because of lack of program
      organization, structure, and funding. Lack of sufficient funding, public
      education, organization of screening, training, and government support were
      listed as barriers to preschool vision screening. CONCLUSION: Providers are
      interested in the development of structured screening programs. However, although
      screening may be a way to offer some level of vision care service to low health
      care access areas, a number of factors need to be addressed in discussions of
      vision screening program standards or screening best practice. In general,
      preschool screening programs need to be structured, be supported, have quality
      control, and be evaluated.

PMID- 15252356
TI  - A comparison of autorefractor performance.
AB  - PURPOSE: To compare the agreement between subjective refraction and
      autorefraction using two commercially available autorefractors. METHODS:
      Prospective data were collected for 190 subjects using either the Nidek ARK-700A
      (Fremont, CA) or the Topcon KR-8000 (Paramus, NJ) and subjective refraction
      (masked to autorefraction). Refractions were compared in terms of spherical
      equivalent using Bland-Altman limits of agreement and astigmatic vector
      difference using median and 95th percentile. RESULTS: The two groups were similar
      for age, gender, spherical equivalent, and astigmatic power. The differences in
      spherical equivalent between subjective and autorefraction were significantly
      different (mean +/- SD; Nidek, -0.03 +/- 0.36 D; Topcon, +0.11 +/- 0.34 D;
      analysis of variance, F = 7.84; p < 0.01). However, the 95% limits of agreement
      were similar: Nidek, -0.74 to +0.68 D; Topcon, -0.55 to +0.77 D. The median
      differences in astigmatic vector difference were also similar: Nidek, 0.27 D and
      Topcon, 0.25 D. However, the 95th percentile was 0.67 D for Nidek and 1.09 D for
      Topcon. There was a low frequency of large (>1.00 D) differences in spherical
      equivalent, 1.1% with each autorefractor. There were five cases with astigmatic
      vector difference >1 D, all with the Topcon KR-8000 (5.3%). CONCLUSIONS: Both
      autorefractors show excellent agreement with subjective refraction. Despite a
      statistically significant difference in mean spherical equivalent (0.14 D), near
      identical limits of agreement (0.10 D difference) suggest clinical equivalence.
      Conversely, for astigmatism, despite similar median scores, major outliers were
      more likely with the Topcon, reflected in a 0.42 D larger 95th percentile, which
      suggests a small advantage for the Nidek for avoiding large astigmatic errors.

PMID- 15252357
TI  - Induced aniseikonia diminishes binocular contrast sensitivity and binocular
      summation.
AB  - PURPOSE: To study the effect on binocular contrast sensitivity and binocular
      summation of aniseikonia induced by size (afocal) lenses. METHODS: In 18 young
      emmetropic observers, the monocular and binocular contrast sensitivity function
      was measured under normal conditions and after inducing different degrees of
      aniseikonia (2%, 3%, and 5% and for 6 observers, 8%) in the right eye. The
      spatial frequencies tested were 2.4, 3.7, 6.0, 9.2, 12, 15, 20, and 24 cpd.
      RESULTS: The results reveal a significant decline in binocular contrast
      sensitivity and binocular summation for 5% aniseikonia, this decline being more
      pronounced for intermediate and high spatial frequencies. CONCLUSIONS: These
      results, together with others on different binocular functions, show the
      importance of aniseikonia in binocular vision. On this basis, we recommend that
      aniseikonia be considered in surgical processes such as cataract and refractive
      surgery, whereby aniseikonia could be induced and binocular performance
      subsequently diminished.

PMID- 15252358
TI  - 10 most commonly asked questions about the use of opioids for chronic pain.

PMID- 15252359
TI  - Parkinsonism.

PMID- 15252360
TI  - A golden opportunity to "prove your worth".

PMID- 15252361
TI  - Interstate practice.

PMID- 15252362
TI  - The emergency department case manager: effect on selected outcomes.
AB  - The purpose of this research is to examine the effect of having nursing case
      managers (NCMs) assigned in the emergency department (ED). This research
      evaluates criteria from the following aspects: inappropriate admissions to the
      intensive care unit precertification of admissions to the hospital, intensive
      case unit diversion rates for the hospital, cost savings, and staff and patient
      satisfaction. The method utilized was a pretest and posttest design examining
      data on several variables before and after placing the NCMs in the ED. The time
      frame for the study is 1 year in an urban, 534-bed acute care teaching facility.
      NCMs were assigned to the ED 7 days a week and were responsible for
      precertification for admissions and working with physicians to determine that
      patients are admitted to the most appropriate level of care. Data will be
      collected through a variety of sources.

PMID- 15252364
TI  - Case management and the national quality agenda: partnering to improve the
      quality of care.
AB  - The national quality agenda has received a great deal of public attention and
      hospital leaders are turning to case management departments for solutions. The
      purpose of this article was to review the evolution of the national initiative
      and to describe how case management programs-regardless of the setting-can
      demonstrate their value to their organization through embracing the core
      measures. The author discusses what barriers currently exist in systems that
      prohibit organizations from achieving 100% performance on core measure
      indicators. The Case Management Standards of Practice will provide a framework of
      discussion identifying why case managers should participate in the improvement
      process. And, finally, the author will discuss suggested strategies case managers
      can implement in their practice.

PMID- 15252365
TI  - Case management in the Canadian Forces.
AB  - Changes in the Canadian military healthcare structure, and an increased reliance
      on the public healthcare sector, resulted in care fragmentation and a growing
      dissatisfaction among members with the quality of health services. To remedy the
      situation, the Canadian Forces began a major re-engineering of its healthcare
      services. A component of this reform was the implementation of a case management
      program to improve the continuity of care for members with complex or chronic
      medical conditions. Member satisfaction surveys revealed that the case management
      program meets their needs.

PMID- 15252366
TI  - Discharge planning: a collaboration between provider and payer case managers
      using Medicare's Conditions of Participation.
AB  - Discharge planning is a legally mandated function for hospitals and is one of the
      "basic" hospital roles as outlined in Medicare's Conditions of Participation.
      This article will define discharge planning; describe the steps in the discharge
      planning process; list rules and regulations that influence discharge planning in
      hospitals; and compare hospital-based actions with payer-based actions when
      planning discharges. Case managers who work for payers interact with hospital
      based case managers to facilitate the discharge planning process for patients.
      Those who form this patient-provider-payer triangle will benefit by reviewing the
      dynamics of the discharge planning process.

PMID- 15252367
TI  - Case managers getting it done: a project management primer.

PMID- 15252368
TI  - Documentation: a guide for case managers.

PMID- 15252369
TI  - A pilot project: the impact of case manager performing inpatient rehabilitation
      reviews.

PMID- 15252370
TI  - Severely head-injured children: treatment and dilemma.

PMID- 15252371
TI  - SIAARTI-SARNePI Guidelines for the management of severe pediatric head injury.

PMID- 15252372
TI  - Observational study on the use of remifentanil in general anesthesia. Drug
      utilisation research.
AB  - AIM: The use of remifentanil in routine clinical practice during the induction
      and maintenance of general anesthesia as well as the quality of awakening after
      anesthesia and post-operative pain management have been assessed. METHODS: A
      total of 123 Italian anesthetists were involved; data of 1 295 patients (ASA I
      IV) undergoing surgical interventions (range duration of intervention 30-240
      min), in which remifentanil was used according to internal anesthesiologic
      procedures, have been collected. The most common modality of anesthesia induction
      is to use a syringe pump to start remifentanil administration. The remifentanil
      dosage mainly used to start the infusion was 0.2 mg/kg/min (29.2% of patients),
      as well as at the beginning of maintenance of anesthesia (35.1%). RESULTS: During
      maintenance of anesthesia, 36% of surgical interventions did not need changes of
      remifentanil infusion rate, whereas in the rest of the intervention 1 to 4
      changes were done. The induction of anesthesia is predominantly intravenous with
      concomitant use of propofol and TPS, whereas the agents most frequently used
      during maintenance were sevoflurane (49.8%), nitrous oxide (43.7%) and propofol
      (35.2%). Awakening was mainly judged rapid in 93% of interventions; the
      postoperative pain at awakening was judged nil in 61% of cases and severe in
      1.5%. The administration of analgesic treatment mainly started prior to the end
      of intervention (70% cases). CONCLUSION: This Drug Utilisation Research study
      demonstrated that the use of remifentanil according to its peculiar
      pharmacological profile, such as potent opioid with rapid onset and offset of
      action, the synergistic effect with propofol and the right management of post
      operative pain are widely consolidated in Italian clinical practice.

PMID- 15252373
TI  - Heat stress: characteristics, pathophysiology and avoidable mistakes.
AB  - In August 2003 an exceptional heatwave was recorded in Europe. The authors would
      like to describe 6 patients for which the intensivist was called as a consultant.
      All patients had a skin temperature >40 degrees C, central nervous system
      impairment, severe hyponatremia [124.7 mEq/l+/-5.6 (range 117-130)] and severe
      metabolic acidosis [BE -6.28 mEq/l+/-3.55 (range -9.5-0), HCO3- 17.75 mEq/l+/
      3.25 (range 13.4-21.9)]. All patients had decreased platelet count and
      coagulation abnormalities. Two patients were hypertensive, 4 hypotensive. The
      heat stress due to the hot environment is characterized by systemic inflammatory
      response (as in severe sepsis) and hemodynamic impairment (as in hypovolemic
      shock). The association between hypovolemia and altered microcirculation leads to
      cell energy failure with metabolic lactic acidosis. The energy failure may induce
      structural irreversible damage of mitochondria. It is possible to differentiate,
      during energy failure, the irreversible or reversible condition by volume loading
      and vasoactive drugs challenge tests. In fact, if the hemodynamic correction is
      associated with normalization of SvO2 with disappearance of metabolic acidosis,
      this suggests hemodynamic impairment with intact mitochondrial function. In
      contrast, if the hemodynamic improvement with normalization of SvO2 is associated
      and acidosis persists, this suggests irreversible structural mitochondrial
      damage. The threshold between reversibility and irreversibility is likely time
      dependent, as suggested by biochemical consideration and by 2 large randomized
      studies on hemodynamic treatment. The comparative analysis of these 2 studies
      suggests that the time of intervention may lead to significant differences in
      mortality. In these patients time is essential.

PMID- 15252374
TI  - [Guidelines for the diagnosis of childhood obstructive sleep apnea syndrome].

PMID- 15252375
TI  - The management of type 2 diabetes in children and adolescents.
AB  - The medical community faces an emerging epidemic of type 2 diabetes (T2DM) in
      children and adolescents with a disproportionate increase among certain ethnic
      groups. T2DM represents one arm of the metabolic syndrome and parallels an
      increasing prevalence of obesity. The metabolic syndrome includes insulin
      resistance, hyperlipidemia, and hypertension with a consequent risk of early
      cardiovascular disease. Thus, treatment of T2DM and the metabolic syndrome pose a
      challenge for pediatric endocrinologists and represent an enormous public health
      issue. This review presents information about the treatment of childhood T2DM.

PMID- 15252376
TI  - Pediatric obesity prevention and management.
AB  - Obesity has reached epidemic proportions worldwide in turn redirecting the goals
      of the Pediatric well care visit. There is no effective pharmacological or
      surgical treatment available for this entity but if left unaddressed it can lead
      to detrimental medical complications. Several known contributors to obesity exist
      which allow the development of successful prevention programs. Prior to
      initiating such a program, a pediatric practitioner should be equipped with the
      skills of identification of overweight and its risk factors as well as strong
      knowledge of treatment options. We attempt to provide the appropriate guidelines
      for childhood obesity prevention in this review.

PMID- 15252377
TI  - Prevention of adverse events in juvenile diabetes.
AB  - The most severe adverse event of juvenile diabetes is death. Still these days it
      happens that children with diabetes die from diabetes before having received any
      treatment at all, sometimes probably undiagnosed. We have to improve the
      awareness and knowledge, both in the general population and also among health
      care staff and physicians. Retarded growth and development was seen earlier, but
      is now rare. But long-term complications affecting primarily blood vessels and
      nerves are still a real threat and may develop already after a few years. Unless
      diabetes is well treated, the disease is as dangerous as ever before. We know
      that a good metabolic control prevents complications, but not how to reach such
      control in many patients. Severe hypoglycemia has been feared to limit our
      possibilities to reach good metabolic balance. However, near-normal HbA1c must
      not be accompanied by increasing incidence of severe hypoglycemia. Too many
      patients are never offered an insulin treatment as physiological as possible.
      Adequate use of basal and bolus insulin is a prerequisite. Continuous adjustments
      should be monitored on the basis of glucose profiles, but without effective
      education and psychosocial support the treatment tends to fail. Intense treatment
      of diabetes may become a heavy burden, an "adverse event" in itself, for the
      patient and the parents of a diabetic child. Psychosocial support is often
      needed. Realistic information already from the onset of the disease is important,
      together with optimism, encouragement and not only criticism. Short-term goals
      and realistic agreements may help the patient to accept the disease. Independence
      and capacity to manage the treatment successfully contribute to a good metabolic
      control and also improves quality of life. Children with diabetes cannot expect a
      "normal" life, but they should be able to expect a long, active, exciting and
      happy life.

PMID- 15252378
TI  - Adolescent alcohol use and injury. A summary and critical review of the
      literature.
AB  - BACKGROUND: Survey research indicates that alcohol use and misuse by adolescents
      is prevalent worldwide and has been associated with multiple negative health,
      social, and economic consequences. Physical injury is one of the negative
      consequences of alcohol use that appears to be on the rise among adolescents.
      METHODS: A retrospective review was conducted of published data currently
      available regarding alcohol use and injury among adolescents. Studies were
      reviewed if 1) the sample included adolescents between the ages of 13 and 19
      years, 2) the study site was a medical setting, and 3) data were collected
      regarding alcohol ingestion. RESULTS: Data indicate that rates of adolescent
      alcohol use range from 5% among general emergency department (ED) admissions to
      nearly 50% among trauma admissions. Alcohol-positive adolescents are more likely
      than alcohol-negative adolescents to be injured, have a prior history of injury,
      require trauma service care, and have injury complications. One-third to one-half
      of alcohol-positive adolescents are referred for or receive intervention related
      to their alcohol use. CONCLUSIONS: Alcohol use by adolescents is associated with
      increases in severity of injury and cost of medical treatment. Screening of
      adolescent trauma unit admissions for alcohol use might be justified based on the
      literature. Optimal methods of screening, identification, and brief intervention
      for alcohol abusing adolescents within the medical setting are discussed.

PMID- 15252379
TI  - [Hypertension in schoolchildren: research carried out in a secondary school in
      Rome and observations on dietary patterns].
AB  - AIM: The aim of this research was to evaluate the incidence of hypertension in
      adolescents by assessing their anthropometric measurements and diet, since recent
      literature data suggest that 30% of obese adolescents are hypertensive. METHODS:
      The 293 schoolchildren engaged in the study were aged 11-14 years and 54% were
      male. They attended a Secondary School in Rome with a middle-high class
      background. Blood pressure, heart rate, weight, height, tricipital and
      subscapular skinfolds and body mass index (BMI) were measured and dietary
      patterns assessed through 24-h recall. The findings were then statistically
      evaluated. RESULTS: The incidence of hypertension was 6.5%, without distinction
      between sexes. On the basis of the statistical evaluation of the correlations
      between hypertension and obesity, familial hypertension, weaning with the
      addition of salt and bottle-feeding from birth, only obesity was found to be
      statistically significant (p<0.001). Even though the hypertensive adolescents had
      a high intake of snacks, salt, meat, sausages and cheese in their daily diet,
      only the excess of proteins was statistically significant (p<0.05). The incidence
      of obesity (calculated as being 20% over the ideal weight for a given height) was
      17.3%. This finding was confirmed by the mean value of the both skinfolds,
      whereas BMI, for which obesity and overweight were considered together, showed a
      slight overestimation of this percentage. CONCLUSION: A high number of
      hypertensive adolescents was found, about 1/3 of the obese adolescents examined.
      This confirms the findings of an extensive study previously carried out by the
      Group of Hypertension of the Italian Society of Pediatrics. From a nutritional
      point of view, the excessive intake of proteins of the 19 hypertensive
      adolescents was found to be statistically significant. However, a more extensive
      study could probably provide further data on other nutrients which, in this case,
      were not quite statistically significant.

PMID- 15252380
TI  - [Survey of physical activity and doping in a sample of 6,915 students aged 14-18
      years].
AB  - AIM: Promoting physical activity is one of the main goals of health-promotion
      policies. The period of adolescence is characterised by a high rate of
      abandonment of any physical activity. In this age range, moreover, the risk of
      assuming substances in order to improve muscular-mass or athletic results is
      concrete. This study quantifies the involvement in physical activities and
      substance assumption in a sample of 6915 students aged 14 to 18 years and living
      in 7 different areas, mostly in northern Italy. METHODS: The survey's tool is an
      adapted and modified vision of the Youth Risk Behaviour Surveillance
      questionnaire, created by US Centers for Disease Control and Prevention (CDC).
      RESULTS: The study showed a high percentage of the sample not involved in any
      form of physical activity out of school (33.8%), more among girls (44.1%) than
      boys (21.2%). Between 14 and 18 years, a continuous reduction of involvement in
      physical activity is evident, while the percentage of totally physically inactive
      subjects rises from 30.1% to 43%. Finally, 5.6% in our sample admitted to have
      been using substances to improve muscular-mass or athletic results at least once
      in the past. CONCLUSION: According to this study, only a minority of the
      interviewed adolescents is involved in a regular physical activity. In males,
      using substances to improve physical strength showed to be rather diffused.
      Specific health promotion projects are suggested.

PMID- 15252381
TI  - [Tic disorders and arousal dysfunction: clinical evaluation of 49 children and
      adolescents].
AB  - AIM: Tourette Syndrome (TS) shows a significant comorbidity with obsessive
      compulsive disorders, behavioral problems (i.e. attention-deficit/hyperactivity
      disorders) and sleep disturbances. Several studies showed that sleep problems are
      common in TS patients affecting 12% to 62% of patients. Aim of this study was to
      evaluate the relationships between tics, sleep disorders and behavioral
      disturbances. METHODS: Fourty-nine consecutive children and adolescents with tics
      have been studied by the following procedure: a) the Yale Global Tic Severity
      Scale (YGTSS) was administered in order to establish the severity of tics; b) the
      Child Behavior Checklist (CBCL) was used to evaluate behavioural disturbances; c)
      the Sleep Disturbance Scale for Children (SDSC) was filled out in order to assess
      the presence of sleep disorders. An age-matched control group was used for
      comparison. RESULTS: All patients (either TS or non-TS) showed a higher
      prevalence of sleep disturbances versus the control group. Sleep-wake transition
      disorders (SWTD) were the most frequent sleep disturbances found in our sample,
      followed by disorders of initiating and maintaining sleep (DIMS). These latter
      sleep disturbances were highly correlated with the severity of tics.
      Internalization problems, anxiety/depression and attention and thinking problems
      were very frequent in our sample. Correlation analysis showed a positive
      relationship between internalization problems and DIMS and also between
      aggressive behaviour and respiratory disturbances during sleep (RDS). CONCLUSION:
      The results obtained seem to confirm the literature reports on the strict
      relationship between tics and sleep disturbances, mainly SWTD, and further
      support the hypothesis of a dysfunction of arousal mechanism in TS.

PMID- 15252382
TI  - Surgical approach to neonatal intestinal perforation. An analysis on 85 cases
      (1991-2001).
AB  - AIM: Primary gastrointestinal perforations have an incidence of between 1% and 3%
      in NICU patients. The 3 Centers participating in this study cover nearly 40% of
      the NICU population of the Lazio Region--Italy. The aim of this study is to
      discuss factors affecting survival in patients affected by a primary intestinal
      perforation. METHODS: From 1991 to 2001, 67 cases of 85 with a neonatal
      gastrointestinal perforation, were related to primary bowel lesions. Necrotizing
      enterocolitis (NEC) was not always the cause of perforation and in many patients
      an isolated bowel lesion without signs of NEC was found. The aim of this study
      was to examine clinical and intraoperative findings of NEC and non NEC
      perforations and their impact on survival. A relevant number of these patients
      were extremely low-birth weight (ELBW). Controversies about treatment of this
      category of neonates are discussed. RESULTS: Patients were 37 males and 30
      females (mean birth weight 1 274.8 g, mean gestational age 28.9 weeks, mean age
      at perforation 10 days). Overall survival was 56.8%. Patients were divided by
      intraoperative findings in 2 groups: NEC (n=48), or isolated intestinal
      perforation (IIP) without signs of NEC (n=19). Differences between these 2 groups
      with regard to birth weight, maturity, associated cardiac anomalies (patent
      ductus arteriosus, PDA) were significant. NEC and IIP behaved as 2 distinct
      entities, each with peculiar clinical (age at perforation, oral feeding, need of
      ventilatory support) and radiological aspects. At surgery, multiple lesion on
      necrotic bowel were typical of NEC versus single, isolated perforations on
      healthy bowel typical of IIP. Overall survival was almost identical in the 2
      groups (59% vs 58%). ELBW patients (55% of the total neonatal intestinal
      perforations) were also studied. There were 21 patients with NEC and 16 with IIP.
      The 2 groups were different in age at perforation, previous oral feeding and
      associated cardiac anomalies (PDA). Overall survival was 62% for NEC and 50% for
      IIP. A laparotomy was always performed. Temporary peritoneal drainage was done in
      4 cases only. Results were better when intestinal diversion was performed rather
      than resection and primary anastomosis. Almost all NEC patients had multiple
      perforations and extended bowel necrosis. CONCLUSION: NEC is the most frequent
      cause of neonatal intestinal perforation. This is a quite distinct entity from
      IIP, which must always be differentiated preoperatively and which is most
      frequently found among low birth weight newborns. As far as surgical treatment of
      perforation among ELBW neonates is concerned, peritoneal drainage might be
      reasonably performed when a single lesion on healthy bowel as in IIP is clearly
      diagnosed but it could be inadequate for NEC patients.

PMID- 15252383
TI  - Non-specific febrile illness by Coxsackievirus A16 in a 6-day-old newborn.
AB  - A case of non-specific febrile illness by Coxsackievirus A 16 (CA 16) in a 6-day
      old newborn whose mother had developed hand, foot and mouth disease
      manifestations 2 days after delivery is reported. Notwithstanding the concurrence
      of negative circumstances like the presence of the enterovirus genome in the
      cerebrospinal fluid, absence of type specific neutralizing antibody and a few
      days of life, the newborn recovered 3 days after the onset of fever. This case,
      also characterized by the absence of mucosal and cutaneous erythematous
      manifestations typical of CA16 infection, draws attention to the possibility that
      non-specific febrile illness in newborns usually suspected of bacterial origin
      may have an enteroviral cause.

PMID- 15252384
TI  - Sutton's nevus and growth hormone therapy.
AB  - Growth hormone (GH) has been suggested to increase the growth of melanocytic nevi
      and the risk for melanoma in short children treated with substitutive therapy. On
      the contrary, in GH deficient patients the influence of GH treatment on the
      appearance and the long-term evolution of Sutton's nevus, a pigmented melanocytic
      lesion surrounded by a ring (halo) of depigmentation, that usually and
      progressively involves the nevus, is debated. The aim of this study was to
      investigate whether GH therapy causes an accelerated growth of Sutton's nevus. In
      our study, we evaluated 3 children with GH deficiency sharing Sutton's nevus to
      investigate the relationship between these melanocytic lesions and growth
      hormone. In case 1 the appearance of the nevus could be induced by hGH therapy.
      However, the lesion did not change in shape, colour and size even if he entered
      puberty during substitutive treatment. Moreover, Sutton's nevus is present in
      case 2, who is prepuberal and not yet treated with hGH. In case 3 Sutton's nevi
      occurred during GH treatment and after the onset of puberty, but didn't show any
      long-term change in both the number and size. No clear influence of both GH
      therapy and sexual steroids on Sutton's nevi was observed.

PMID- 15252385
TI  - [Successful treatment of Norwegian scabies with ivermectin in a patient with
      recessive dystrophic epidermolysis bullosa].
AB  - A 14 year-old female born from consanguineous healthy parents was admitted to our
      institute for the presence of a generalized bullous eruption started at birth.
      The bullae were asymmetrically distributed all over the cutaneous surface and,
      over time, evolved into erosions that resolved with scarring areas. On the basis
      of the clinical picture and the ultrastructural and antigenic studies, a
      diagnosis of recessive dystrophic epidermolysis bullosa was made. In the
      following months, the patient began to complain a severe pruritus and the bullae
      and erosions were accompanied with diffuse erythematous patches and plaques
      covered by thick scale-crusts situated mostly on the arms. Microscopic
      examination of the scales revealed the presence of many mites and ova. Since the
      conventional topical therapies for scabies were uneffective, the patient was
      treated with a single dose (200 mcg/hg) of ivermectin. Although there was an
      initial improvement, scabies recurred within 2 months from discontinuation of the
      therapy. Finally, a further single administration of ivermectin at the same
      dosage led to the complete and permanent resolution of scabies. The association
      of recessive dystrophic epidermolysis bullosa and norwegian scabies has been
      already reported in literature. The case presented suggests that ivermectin
      represents an effective drug for severe forms of scabies occurring in patients
      affected by other dermatoses that prevent the use of topical treatments.

PMID- 15252386
TI  - Surgical applications of organ preconditioning.
AB  - In 1986, Murry et al. reported that brief periods of antecedent ischemia in dogs
      paradoxically reduced (rather than exacerbated) the size of myocardial infarcts
      created by subsequent prolonged ischemia. This fortuitous discovery, now termed
      "preconditioning", stimulated further investigation of the inherent adaptive
      mechanisms present in a variety of tissues and organs. In addition to ischemia,
      it is now recognized that a protective response can be initiated by multiple
      means including lipopolysaccharide, heat stress, exercise, adrenergic drugs and
      even noise. Furthermore, preconditioning protects not only against cell death but
      also against postischemic contractile dysfunction, stunning and arrhythmias.
      Despite the preponderance of animal studies demonstrating the benefits of
      preconditioning, its clinical application has been hampered by clinicians'
      hesitancy to intentionally subject patients to a noxious stress prior to a
      planned intervention. However, many of the intracellular signals responsible for
      the protective effect of preconditioning have been delineated, and pharmacologic
      manipulation of these signals can accomplish the same benefits. The existence of
      preconditioning in humans has been demonstrated in vitro and in small clinical
      trials, and targeted strategies that exploit this endogenous protective mechanism
      promise to broaden the therapeutic potential of organ preconditioning.

PMID- 15252387
TI  - Gastrointestinal stromal tumors of the stomach.
AB  - Gastrointestinal stromal tumors (GIST) comprise a rare group of neoplasms of
      unpredictable malignant potential with an annual incidence of 4/million persons.
      The stomach is the most common site of occurrence in the gastrointestinal tract.
      A combination of prognostic factors (patient age, histologic grade, mitotic rate,
      tumor size, and DNA analysis) have been utilized to predict their biologic
      behavior. Lymphatic spread of gastrointestinal stromal tumors is uncommon
      therefore a formal lymph node dissection is not standard surgical management.
      Consequently, complete surgical resection of the primary tumor is the most
      definitive treatment. An increasing number of cases have been reported utilizing
      a combination of laparoscopic and endoscopic techniques to resect these tumors.
      The manuscript will characterize the biologic behavior of gastrointestinal
      stromal tumors of the stomach, discuss the preoperative evaluation and minimally
      invasive surgical management of these patients, and review recent, encouraging
      adjuvant treatment strategies.

PMID- 15252388
TI  - [Radical peritonectomy in 37 patients with stage II and III ovarian cancer].
AB  - AIM: Radical peritonectomy followed by intraperitoneal early chemotherapy and
      systemic chemotherapy is the treatment of choice of stage II C and III ovarian
      cancer, due to the low 5-years survival rate (20%) of stage III and IV. METHODS:
      The authors present a 5-years experience in 37 patients affected by stage II C
      and III ovarian cancer treated by Sugarbaker's radical peritonectomy with some
      surgical technical differences. Intraperitoneal chemotherapy with adriamycin and
      cisplatin is started and followed after 25 days by a systemic chemotherapy with
      taxol and carboplatin. A 6-months second-look is performed. RESULTS: All the
      patients have been treated with radical peritonectomy with tumoral residual
      lesser than 2.5 mm; we performed 4 minor hepatectomies, 5 radical cystectomies,
      35 resections of rectum and sigmoid colon with hysterectomies, bilateral salpingo
      oophorectomies and pelviperitonectomies, 14 right hemicolectomies. We had no
      postoperative mortality, but we recorded a 40% minor morbidity rate. During the
      second look we found 7 recurrences (18%), 6 lesser than 6 mm, often located on
      the mesentery and treated with radical resections. The follow-up range is 2-60
      months, 27 patients are still alive. Actually, 22 patients (80% of live patients)
      are in good health and disease free. CONCLUSION: Radical surgery associated with
      early postoperative chemotherapy followed by systemic chemotherapy in the
      treatment of ovarian cancer makes it possible to achieve the best survival
      results and long periods of disease free.

PMID- 15252389
TI  - [Neoplastic residues in the trocar tract in oncologic laparoscopic surgery].
AB  - AIM: The laparoscopic approach to malignant diseases runs up against both old and
      new problems: respect for the principles of radicality, operating times, the
      postoperative course and surgical complications, long-term oncological results in
      terms of survival and recurrence of the disease. One of the problems which has
      received most attention regards the onset of a metastasis on a trocar scar or a
      mini-laparotomy recurrence. Trocar site tumor recurrences have been described in
      the literature following laparoscopic surgery in almost all abdominal malignant
      pathologies (colorectal, gynaecological, pancreatic, etc.) and even after
      thoracoscopy. The real frequency is currently of the order of 1% (0-2%) in colic
      surgery and of 14% (10-17%) after cholecystectomy for occult gallbladder
      carcinoma. METHODS: A retrospective survey was carried out of our laparoscopic
      experience; between 1994 and 2002 213 colic resections were carried out for
      cancer; we also observed 18 occult carcinomas of the gallbladder in 2386
      laparoscopic cholecystectomies for lithiasis. RESULTS: Respectively 2 cases (11%)
      of trocar site neoplastic recurrences in gallbladder carcinoma and 2 cases (0.9%)
      from colon carcinoma were observed. CONCLUSIONS: The real extent of the problem
      would appear to be on a much lesser scale at the moment than was initially
      thought, especially as regards colic surgery. The multifactorial aetiology of the
      problem explains the importance of their prevention, on the basis above all of
      rigorous respect for the rules and protocols of laparoscopic technique.

PMID- 15252390
TI  - [Endoscopic palliation of inoperable hilar biliary carcinoma with self-expanding
      metal stents].
AB  - AIM: Prosthetic palliation of patients with malignant hilar stenoses shows
      particular difficulties, especially in advanced lesions. This is a prospective
      report of the efficacy of endoscopically inserted single metal stent for complex
      malignant biliary hilar obstruction. METHODS: Sixty-one consecutive patients were
      recruited. Contrast injection was deliberately limited to the distal end of the
      malignant tumor stenosis. A single metal stent was inserted across the stricture
      into the duct that was technically easiest for the drainage. RESULTS: Successful
      stent insertion was achieved in 59 of 61 (96.7%) patients. In 3 (4.9%) cases
      stent malfunction occurred. Successful drainage was achieved in 59 (96.7%)
      patients and complete resolution of jaundice was achieved in 86% of cases. Early
      complications included 3 (4.9%) cases of cholangitis and 2 (3.2%) cases of stent
      occlusion. Late occlusion of the stent occurred in 14 patients (22.9%), including
      10 (16.3%) cases of cholangitis and 1 case of liver abscess. Median stent patency
      was 169 days. Median patient survival was 140 days. CONCLUSION: Metal stent
      insertion is safe, feasible, and achieves adequate drainage in the great majority
      of patients with non-resectable hilar cholangiocarcinoma.

PMID- 15252391
TI  - The TramEC "double cross" mesh: a new experience for repairing groin hernia. Our
      experience with 280 patients.
AB  - AIM: The purpose of this work is to provide a detailed account of a new technique
      for open prosthesis hernioplasty, a technique that makes use of a pre-shaped
      TramEC mesh made of polypropylene monofilament and created by the author.
      Specific descriptions are offered in regard to the shape of the mesh, the
      hernioplasty technique and the physiopathologic characteristics. METHODS: From
      2000 to 2001, a total of 280 hernioplasties were performed with the TramEC
      technique. A follow-up of these patients was done after 1 week, after 3 months
      and after 1 year. An ecography of the groin was executed on all patients after 1
      week in order to verify the presence of seromas. RESULTS: No recurrence was
      observed in 55.7% of patients examined after 1 year. Two patients (1.2%)
      experienced chronic but not debilitating pain. CONCLUSION: The author believes
      that with the TramEC mesh a precise overlap is formed between the mesh itself and
      the floor of the groin canal, thus creating the conditions required for avoiding
      empty spaces in order to favour the fibroplasias and amalgamation of tissues:
      basic parameters in avoiding recurrences. In addition, the mesh not only repairs
      the hernial defect but also strengthens the internal inguinal ring by virtue of
      its "double cross" structure. Because of the device's anatomical shape and the
      simplicity of the technique, we optimise the operation in terms of time and
      reproducibility.

PMID- 15252392
TI  - [Laparoscopic transabdominal preperitoneal repair of inguinal hernia:
      indications, technique, complications and results in 10 years experience].
AB  - AIM: Inguinal hernia play a major role in a general surgical division. In the
      last 10 years laparoscopy has gained a key role even in the treatment of this
      disease. This study aims to review a single institution's experience with
      laparoscopic transabdominal preperitoneal repair of inguinal hernia (TAPP).
      METHODS: A retrospective study of 715 operations in 500 patients from 1992 to
      September 2002. Two hundred and eight six (56.6%) of these were monolateral
      hernias and 214 (43.4%) were bilateral while 215 (30%) were recurrent. RESULTS:
      Of 214 operations recurrence rate was 0.43 with a mean operating time of 30 min
      (range 25-50) for monolateral hernias and of 70 min (range 45-120) for bilateral
      hernias. Mean length of stay was 2 days (range 1-10). Return to work occurred in
      6 days while sports were resumed after 10 days. Complications occurred in 40
      (8.6%) patients with only 2 (0.4%) major complications. Mean follow up time was
      58.3 months. CONCLUSION: According to personal experience, and in agreement with
      international literature, laparoscopy showed to be effective mostly in treating
      bilateral and recurrent hernias, particularly for faster recovery and less
      postoperative pain compared to traditional techniques.

PMID- 15252393
TI  - [Inguinal hernia in the elderly. Indications, techniques, results].
AB  - AIM: Inguinal hernia in the elderly is a quite common problem in general surgery.
      Surgical treatment must be aware of the cardiovascular and respiratory pathology
      these patients are often affected by and, on the other side, the goal of surgery
      is a quick functional recovery after the operation using the "tension free"
      technique and, whenever possible, local anesthesia. In this paper personal
      experience on inguinal hernioplasty in elderly patients (>65 years) is presented;
      the aim is a better definition of the indications to surgery and anesthesia and
      verify the results of surgical treatment. METHODS: From January 1999 to December
      2002 our group operated 317 patients with inguinal hernia; 123 patients were over
      65 (119 male, 4 female, age from 65 to 101 years, mean 74); in this group 111
      Lichtenstein and 12 Trabucco HPL were performed. There were 89 primitive hernias,
      17 recurrences and 17 emergency operation. Local anesthesia was the method of
      choice except for obese patients, obstruction or strangulation, or patient's
      preference. In giant hernia, or when a large sac was found, the Wantz technique
      was performed (13 patients); a suction drainage was used if a large space in the
      inguinoscrotal area remained after hernia reduction (9 patients). RESULTS: Local
      anesthesia was used in 87 patients, spinal in 31 and 5 in general; there were no
      postoperative deaths. Local complications were: 4 inguinal hematomas, 2 hematomas
      and 2 transient edemas of the scrotum, 1 wound infection, 1 sieroma of the wound
      and 1 scrotal sieroma (9%); all patients recovered after few days of medical
      therapy. No cases of ischemic orchitis occurred. CONCLUSION: Inguinal
      herniorraphy can be safely performed, in elderly patients; according to personal
      experience local anesthesia proved to be a safe technique, also in patients with
      cardiocirculatory problems. Local complications were mild and more frequent in
      patients "over" 65 years (13% vs 6%, in "under" 65), but recurrent hernias make
      the difference; a suction drainage can reduce the problems caused by a fluid
      collection in the inguinoscrotal area. Wantz technique reduces the operative time
      and, according to personal opinion, contributed to lower ischemic testicular
      complications to zero.

PMID- 15252395
TI  - [Surgical therapy of Crohn's disease: observations on 63 patients].
AB  - AIM: The purpose of our retrospective study is to evaluate the correct
      indications for the surgical therapy of Crohn's disease. METHODS: Our case series
      consists of 63 patients admitted to our Surgery Department from January 1, 1973
      to December 2002 with a diagnosis of Crohn's disease. Of the 56 operated
      patients, 43 patients were followed-up. For an objective evaluation of the
      Crohn's disease activity, the Crohn's Disease Activity Index (CDAI) was used.
      Surgical treatment has been carried out in 56 cases: in 29 cases of intestinal
      occlusion a minimal gut resection was performed; in the 26 cases of perforation a
      suture of the perforation was preferred, with a drainage of the peritoneal cavity
      and a toilette of abscess when it was present, and in 1 case an ileocolic
      resection was performed. RESULTS: Only 1 case showed a CDAI score >150 (153.63).
      This shows that in all the other cases the surgical and medical treatment has led
      to a satisfactory control of the disease. A relapse has been observed in 17
      patients after an average period of 5 years without showing signs of disease.
      CONCLUSION: It is suggested that Crohn's disease therapy should be mainly of a
      medical nature and surgical treatment should be reserved for complicated cases.

PMID- 15252394
TI  - [Surgical treatment of umbilical hernia in children. Our experience].
AB  - AIM: To identify the main parameters which, differently correlated, indicate in
      which case, age and modality umbilical hernia in children should be surgically
      repaired. METHODS: The authors report personal experience on 319 children with
      umbilical hernia observed in the last 7 years. In 72 cases, on the basis of the
      evaluation of some parameters, a surgical correction was performed with the
      technique described. RESULTS: All the procedures were performed in "day surgery".
      There were no early complications, neither anesthetic nor surgical. All children
      showed a good recovery of all functions (feeding, intestinal canalization,
      walking about) and activities. No middle and long-term complications were
      observed. CONCLUSIONS: Umbilical hernia needs a surgical repair only in a few
      cases and after a careful evaluation of some parameters (age, sex, kind of
      hernia, size and consistency of the hernial porta, protrusion and expansion). The
      surgical procedure should guarantee either the safe and prompt repair or the
      cosmetic result; the use of some devices (anesthetic and surgical) allow to
      obtain excellent results.

PMID- 15252396
TI  - [Surgical treatment in day surgery of uncertain breast lesions].
AB  - AIM: New models of care are proposed to reduce the costs of traditional
      hospitalization and to improve the utilization of resources in surgery. Day
      surgery is widely employed in breast surgery. In this study we report the
      conversion rate and causes in ordinary hospitalization and we identify some
      contraindications related to breast surgery in day surgery. METHODS: A cohort
      study was performed on 306 patients operated on between July 1999 and December
      2001 for breast lesions with uncertain interpretation at the clinical and/or
      instrumental examination. Those patients who lived at a distance of less than 50
      km from the hospital, had a telephone, a suitable house, direct family support
      and, if necessary, could benefit from home health care in addition to
      hospitalization, were considered as eligible to day surgery. The kind of
      anesthesia and hospital admission were established after clinical, psycho
      emotional, and socio-familiar evaluation of the patients by the surgeon and the
      anesthetist. RESULTS: A total of 250 excisional biopsies and 56 biopsies with a
      Mammotome were performed. Surgery was performed under local anesthesia in 278
      patients and general anesthesia in 28 subjects. Observation exceeding 24 hours
      was only necessary in 10 patients reporting hypotension syndrome and anxiety. The
      conversion rate in ordinary hospitalization was 0.3%. Postoperative morbidity was
      1%. CONCLUSION: Day surgery is an effective model of care in breast surgery for
      diagnostic and therapeutic purposes without axillary dissection. A good selection
      of patients, perfect interdisciplinary collaboration, and an efficient structural
      organization are necessary to control the complication and conversion rates of
      traditional hospitalization.

PMID- 15252397
TI  - [Role of CT/111In-octreotide SPECT digital fusion imaging in the localization of
      loco-regional recurrence of medullary thyroid carcinoma].
AB  - The case of a female patient affected by a sporadic medullary thyroid carcinoma
      (pT1N1aM0 at the onset) is reported. The patient had been initially treated by
      total thyroidectomy and lymphadenectomy of the central and lateral portions of
      the neck. During the following 30 years of follow-up, the patient experienced 3
      consecutive loco-regional tumoral relapses. At the moment of each relapse, an
      increase of serum calcitonin levels has anticipated the subsequent detection of
      tumor deposits at clinical and radiological examination (ultrasound, CT scan). It
      is well known that, after multiple operations, the structures of the neck can
      present anatomical distortion and fibrosis that can interfere with ultrasound and
      CT scan interpretation. In the present patient, a scintigraphic examination with
      111In-octreotide, that is a specific radio-tracer for somatostatin receptors,
      allowed to correctly visualize a tumoral relapse in the left thyroid bed, located
      in deep para-tracheal planes: in that site the CT scan only showed an unspecific
      solid mass. Furthermore, the utilization of a digital image fusion technique for
      CT scan and 111In-octreotide SPECT, furnished useful information for the purpose
      of planning an accurate re-intervention, both morphologic information (mass size,
      precise site of the mass and their relationship with the surrounding anatomical
      structures) and functional information (biological characterization of the mass
      that was classified as a neuroendocrine tumoral deposit with high density of
      somatostatin receptors.

PMID- 15252398
TI  - Laparoscopic treatment of post-hysterectomy colovaginal fistula in diverticular
      disease. Case report.
AB  - Colonic diverticular disease is a benign condition typical of the Western world,
      but it is not rare for even the 1st episode of diverticulitis to carry
      potentially fatal complications. The evolution of a peridiverticular process
      generally poses problems for medical treatment and exposes patients to repeated
      episodes of diverticulitis, making surgical treatment necessary in approximately
      30% of symptomatic patients. One of the most worrying complications of
      diverticulosis is internal fistula. The most common types of fistula are
      colovesical and colovaginal, against which the uterus can act as an important
      protective factor. The symptoms and the clinical and instrumental management of
      patients with diverticular fistulas are much the same as for patients with
      episodes of acute diverticulitis. Staging of the disease (according to Hinchey)
      should be done promptly so that the necessary action can be taken prior to
      surgery, implementing total parenteral nutrition (TPN), nasogastric aspiration
      and broad-spectrum antibiotic treatment. The best surgical approach to adopt in
      patients with diverticulitis complicated by fistula is still not entirely clear,
      though the 3-step strategy is currently tending to be abandoned due to its high
      morbidity and mortality rates. There is a widespread conviction, however, that
      the 2-step strategy (Hartmann, or resection with protective stomy) and the 1-step
      alternative should be reserved, respectively, for patients in Hinchey stages 3, 4
      and 1, 2 with a situation of attenuated local inflammation. The 1-step approach
      seems to be safe and effective. This report describes a case of colovaginal
      fistula in a patient with colonic diverticulosis who had recently undergone
      hysterectomy, but who, unlike such cases in the past, was treated in a single
      step using a laparoscopic technique.

PMID- 15252400
TI  - [Ergot-induced upper limb ischemia: surgical treatment].

PMID- 15252399
TI  - [Bronchial arteries: anatomical and clinical studies and strategies in surgical
      approach].
AB  - One of the most important and controversial aspects of thoracic surgery is due to
      the topographical and surgical anatomy of the vascular structures involving the
      mediastinum. The knowledge of the so-called "vascular time", in fact, allows to
      face more complicated surgical situations, typical of the most specialistic
      thoracic surgery. The bronchial arteries represent a paradigm of what we have
      just stated. The study of their anatomy (number, position, origin, distribution
      and relationships with the mediastinal structures) is of relevant importance, not
      only for the interest the bronchial vascular tree arises in tracheo-bronchial
      surgery and in pulmonary transplantology, but also for the knowledge of the
      pathogenesis of some processes regarding pulmonary and pleural pathologies. The
      aim of this paper is to evaluate the real clinical interest of bronchial
      arteries, with an analytic study of the anatomy of vessels, and with the
      possibility to show the most frequent and characteristic anomalies involving the
      origin and course of these arteries.

PMID- 15252401
TI  - Did Ulysses have porphyria?
AB  - Although the biosynthetic pathway to heme has been well elucidated and errors
      along that route have been identified and firmly connected to specific diseases,
      the porphyrias, slight but nonspecific abnormalities, are occasionally invoked as
      proof of porphyria or in support of other diagnoses. An errant patient with a
      conundrum of symptoms but without an explanation for them might have to take
      iatrogenic detours only to learn after what are at times ulyssean vagaries that
      the initial diagnosis of porphyria is in the end untenable. Thus the porphyrias
      are superb examples of the interface between laboratory and clinical medicine, in
      which the occurrence of the Ulysses syndrome can be curtailed through the careful
      ordering of tests and cogent interpretation of their results.

PMID- 15252402
TI  - Medical decision-making and healthcare disparities: The physician's role.
AB  - Widespread disparities in US healthcare have been documented with attendant
      speculation about their causes, including the potential role of the physician as
      a healthcare decision-maker. However, the current evidence on physician decision
      making is inadequate to draw firm conclusions on how it relates to healthcare
      inequalities. In this article, we review the available evidence on physician
      decision-making as it relates to healthcare disparities, with an emphasis on its
      shortcomings, discuss potential sources of bias, including interpersonal factors
      and physician preferences, and make suggestions for further research in this
      area.

PMID- 15252403
TI  - Azithromycin inhibits interleukin-6 but not fibrinogen production in hepatocytes
      infected with cytomegalovirus and chlamydia pneumoniae.
AB  - Chlamydia pneumoniae and cytomegalovirus (CMV) have been associated with the
      development of atherosclerosis. Inflammatory stimuli initiate the biosynthesis of
      fibrinogen, interleukin (IL)-6 and plasminogen activator inhibitor (PAI)-1 in the
      liver. Chronic infection may perpetuate the inflammatory status. We hypothesized
      that infection of human hepatocytes with the intracellular pathogens C pneumoniae
      and CMV accelerates biosynthesis of fibrinogen, IL-6, and PAI-1 but that this
      biosynthesis can be reduced with the use of azithromycin. HepG2 human hepatocytes
      were infected with C pneumoniae and CMV in vitro in the presence of 0, 0.016,
      0.125, or 1 microg/mL azithromycin. We measured IL-6, PAI-1, and fibrinogen after
      24, 48, 72, and 96 hours. C pneumoniae-infected hepatocytes produce IL-6 (2667 +/
      309 pg/mL vs 137 +/- 120 pg/mL in uninfected cells after 96 hours. Incubation
      with 0.016 microg/mL azithromycin decreased IL-6 levels to a mean of 1516 +/- 402
      pg/mL, and incubation with 0.125 and 1 microg/mL azithromycin decreased IL-6 to
      871 +/- 364 and 752 +/- 403 pg/mL, respectively. C pneumoniae-induced IL-6
      production was time- and dose-dependent. The interaction of C pneumoniae with
      azithromycin treatment was significant, indicating an inhibitory effect of
      azithromycin on C pneumoniae-induced IL-6 production. CMV infection did not lead
      to IL-6 production by hepatocytes. C pneumoniae and CMV infection did not induce
      any changes in PAI-1 production. Fibrinogen production was increased by CMV
      infection after 72 hours (838 +/- 88 ng/mL; P <.01) and after 96 hours by
      infection with both C pneumoniae and CMV (765 +/- 100 and 846 +/- 123 ng/mL,
      respectively; P <.05). Azithromycin did not suppress CMV- or C pneumoniae-induced
      fibrinogen production. Moreover, we could not confirm an antiinflammatory effect
      of azithromycin in experiments with cross-titrations of azithromycin against
      either IL-1 or IL-6 (P >.05). Azithromycin reduces C pneumoniae-induced IL-6
      production, but not fibrinogen production, by human hepatocytes. This is a result
      of the antimicrobial properties of azithromycin and not a direct antiinflammatory
      effect.

PMID- 15252404
TI  - A case of hereditary xerocytosis diagnosed as a result of suspected hypoglycemia
      and observed low glycohemoglobin.
AB  - Hereditary xerocytosis is a primary erythrocyte disorder in which a defect in the
      erythrocyte membrane leads to potassium efflux from the cell. An osmotic shift of
      water from the intracellular compartment follows, resulting in decreased
      deformability of the cell, increased membrane rigidity, hemolysis, decreased
      average duration of erythrocyte survival, and reticulocytosis. The condition is
      inherited as an autosomal dominant trait. In this publication, we report the case
      of a patient who presented with a vague history compatible with hypoglycemia and
      was found to have a low glycohemoglobin level. Further workup led to a diagnosis
      of hereditary xerocytosis in this patient and in other members of the family.
      This case illustrates the importance of understanding the underlying variables
      that affect the results of all commonly used glycohemoglobin assays, including
      determination of hemoglobin A(1C) and how primary red-cell disorders may alter
      its value.

PMID- 15252405
TI  - The ratio of plasma to whole-blood serotonin may be a novel marker of
      atherosclerotic cardiovascular disease.
AB  - Because atherosclerotic vascular lesions stimulate platelets, the platelets
      release serotonin (5-hydroxytryptamine, aka 5-HT). We therefore measured 5-HT
      concentrations not only in platelet-poor plasma but also in whole blood as a
      means of assessing vascular lesions. The plasma concentration of 5-HT tended to
      increase with age, whereas that in whole blood decreases. Therefore the ratio of
      the plasma to the whole-blood concentration of 5-HT (P/WB) increases with age.
      This may be a result of the activation of platelets in older subjects with
      atherosclerotic vascular damage. Patients who underwent coronary angiography
      (CAG) were classified into 4 groups according to diagnosis: effort-induced angina
      pectoris (eAP), old myocardial infarction (OMI), vasospastic angina pectoris
      (VSAP), and unstable angina (uAP). The mean plasma 5-HT concentration was
      significantly (P <.01) greater in patients with eAP, uAP, OMI, and VSAP than in
      healthy controls, whereas the concentration in whole blood was lower in patients
      with eAP than in healthy controls. When the P/WB ratios were calculated, the mean
      levels in all disease groups were significantly higher than that in the healthy
      controls. These findings suggested that 5-HT is released into the plasma from the
      platelets and that the concentration in the platelets decreases in patients with
      atherosclerosis.

PMID- 15252406
TI  - Induced sputum methodology: Validity and reproducibility of total glutathione
      measurement in supernatant of healthy and asthmatic individuals.
AB  - Glutathione (GSH), a major antioxidant, has repeatedly been linked to the
      pathogenesis of pulmonary disease. The measurement of GSH in induced sputum (IS)
      offers a noninvasive tool for the study and monitoring of oxidative stress in
      airway diseases. In this study we assessed the validity and reproducibility of
      GSH quantification in IS from healthy subjects and individuals with mild asthma.
      We spectrophotometrically quantified total GSH in the IS of 31 healthy nonsmoking
      volunteers and 12 individuals with mild asthma. IS was processed with varying
      concentrations of dithiothreitol (DTT) in an effort to evaluate the effect of DTT
      on GSH measurements. We performed spiking experiments with defined concentrations
      of GSH and quantified the percentage of recovery and also analyzed the effect of
      induction time on GSH levels through sequential sampling of sputum portions (15,
      30, and 45 minutes' induction). Finally we tested the reproducibility of GSH
      measurements at 2 separate time points (0 and 72 hours) and expressed it as an
      intraclass correlation coefficient (R(i)) with a coefficient of reliability (CR).
      Processing with DTT increased GSH values in IS (P <.05 for each DTT concentration
      > 0.001%). Recovery of GSH after spiking was complete, with a mean recovery of
      102% +/- 4.8%. Increasing duration of induction led to an increase in sputum GSH
      (15 minutes, 10.2 +/- 2.3 micromol/L; 30 minutes, 18.4 +/- 3.5 micromol/L; 45
      minutes, 26.1 +/- 4 micromol/L; P <.05 for all comparisons). Reproducibility of
      sputum GSH both in healthy subjects and asthmatic individuals was good (R(i)
      =.78, P <.001; and R(i) =.51, P =.003, respectively). With the use of
      standardized protocols for duration of induction and sample processing, sputum
      GSH measurement in healthy subjects and asthmatic individuals is valid and
      reproducible.

PMID- 15252407
TI  - Serum oxalate in human beings and rats as determined with the use of ion
      chromatography.
AB  - Previous enzymatic determinations have suggested that serum oxalate
      concentrations in normal rats, the main animal model used in urolithiasis
      research, to be 3 to 5 times greater than those in healthy human subjects. In
      this report we validated this observation using a different method (ion
      chromatography) on serum samples from healthy rats and human subjects that were
      prepared and handled similarly. Oxalate recoveries during sample preparation for
      ion chromatography were strongly and variably affected by ultrafiltration devices
      employed for sample deproteinization and after Cl(-) removal by means of ion
      exchange. When oxalate recoveries were accounted for, we found significant
      differences in serum oxalate (6 human samples, 1.47 +/- 0.15 micromol/L; and 15
      rat samples, 9.88 +/- 0.91 micromol/L). We conclude that ion-chromatographic
      techniques confirm the differences in serum oxalate concentrations between rats
      and human beings measured enzymatically and that failure to account for oxalate
      losses during sample preparation for ion chromatography can lead to significant
      underestimation of serum oxalate in both species.

PMID- 15252408
TI  - Lind's SCURVY trial.

PMID- 15252409
TI  - The role and scope of practice of nurses working in Canadian heart failure
      clinics.
AB  - BACKGROUND: Nurses play an integral role in providing care in heart failure (HF)
      clinics and disease management programs that lead to improved outcomes for HF
      patients. OBJECTIVES: This pilot study explored how closely nurses in Canadian HF
      clinics follow consensus guideline recommendations and nursing interventions from
      published studies. METHODS: A total of 27 nurses from HF clinics across Canada
      completed a questionnaire about their role and scope of practice. RESULTS: The
      majority of nurses covered recommended topic areas for counseling and education
      with the exceptions of discussing advanced directives, teaching patients to
      titrate diuretics, and counseling on secondary prevention. Nurses with a
      postgraduate degree were more likely to independently titrate medications and
      order echocardiograms. Nurses affiliated with the Canadian Congestive HF Clinic
      Network were more likely to provide telephone management, titrate medications,
      and order echocardiograms and other diagnostic tests. CONCLUSION: Patients may
      not be experiencing the benefits that are reported in the literature for being
      followed up in a HF clinic because the role and scope of practice of nurses
      varies from one clinic to another. The role and scope of practice of nurses in HF
      clinics needs to be standardized.

PMID- 15252410
TI  - Home-based exercise improves functional performance and quality of life in women
      with diastolic heart failure.
AB  - BACKGROUND: Diastolic heart failure (DHF) is common in older women. There have
      been no clinical trials that have identified therapies to improve symptoms in
      these patients. A total of 32 women with New York Heart Association class II and
      III DHF (left ventricular ejection fraction >45% and symptoms of dyspnea or
      fatigue) were randomized into a 12-week home-based, low-to-moderate intensity
      (40% and 60%, respectively) exercise and education program (intervention) or
      education only program (control). Methods and results The intervention group
      improved in the 6-minute walk test from 840 +/- 366 ft to 1043 +/- 317 ft versus
      824 +/- 367 ft to 732 +/- 408 ft in the control group (P =.002). Quality of life
      also improved in the intervention group compared with the control group as
      measured by the Living with Heart Failure Questionnaire (41 +/- 26 to 24 +/- 18
      vs 27 +/- 18 to 28 +/- 22 at 12 weeks, P =.002; 24 +/- 18 to 19 +/- 18 vs 28 +/-
      22 to 32 +/- 27 at the 3-month follow-up, P =.014) and the Geriatric Depression
      Scale (6 +/- 4 to 4 +/- 4 vs 5 +/- 3 to 7 +/- 5 at 12 weeks, P =.012; 4 +/- 4 to
      4 +/- 4 vs 7 +/- 5 to 7 +/- 5 at the 3-month follow-up, P =.009). CONCLUSIONS:
      Women with DHF exhibit significant comorbidities and physical limitations. Home
      based, low-to-moderate intensity exercise, in addition to education, is an
      effective strategy for improving the functional capacity and quality of life in
      women with DHF. Further study is needed to assess the long-term effect of
      exercise on clinical outcomes.

PMID- 15252411
TI  - When is a patient with heart failure adequately informed? A study of patients'
      knowledge of and attitudes toward medical information.
AB  - OBJECTIVE: The primary aim was to explore patients' knowledge of heart failure
      and their attitudes toward medical information (prognostic information in
      particular) and to assess different patient-related factors that might hamper the
      improvement of patients' knowledge. Moreover, taking the data obtained into
      account, we analyzed ethical aspects of information disclosure to patients with
      heart failure. SETTING: The study was performed at Sahlgren's University Hospital
      in Gothenburg, Sweden. DESIGN: The study was a qualitative analysis of
      semistructured interviews. PATIENTS: The sample included 40 patients with various
      stages of chronic heart failure. RESULTS: Many patients had only a limited
      understanding of their disease, but they still claimed that they were satisfied
      with the information they received. Some of them seemed to accept, to be
      indifferent to, or to be unaware of their low level of knowledge. The majority
      did not request prognostic information. CONCLUSION: We argue that patients with
      heart failure are adequately informed when they have reached the level of
      knowledge that enables them to be managed as effectively and securely as possible
      while being satisfied with the information provided. To give adequate
      information, health care providers should determine the patients' level of
      knowledge and explore why those patients who have a limited understanding do not
      assimilate or request information.

PMID- 15252412
TI  - Qualitative analysis of the male experience of heart failure.
AB  - OBJECTIVE: The purpose of this study was to gain insight from the patient's
      perspective into how it is to live with moderate chronic heart failure (HF).
      METHODS: Twenty men with moderate chronic HF in New York Heart Association
      classes II to III, aged 43 to 73 years, were interviewed with open-ended
      questions. The interviews were analyzed using qualitative inductive content
      analysis as a method. RESULTS: Both the consequences of the illness and how the
      patients adjusted to them were described in the narratives. The consequences were
      physical, emotional, cognitive, social, and vocational and included thoughts
      about death. Adjusting to the illness involved changing one's lifestyle, being
      aware of one's physical ability and disability, developing psychologic
      strategies, and adjusting to medication. CONCLUSIONS: The findings of this study
      demonstrate a wider range of disabilities as a consequence of moderate chronic HF
      and show several more ways of adjusting to the illness than previously reported
      in men.

PMID- 15252413
TI  - Reversible myocardial ischemia following acute upper airway obstruction.

PMID- 15252414
TI  - Anxiety and health-related quality of life in patients awaiting elective coronary
      angiography.
AB  - OBJECTIVE: The purpose of this study was to document the impact of waiting for
      first-time elective coronary angiography (CA) on patients' anxiety and health
      related quality of life (HRQL). DESIGN: A prospective, observational inception
      cohort pretest and posttest design was used. SETTING: The study was conducted in
      a tertiary community cardiac center in Toronto, Canada. MEASURES: Disease
      specific HRQL was measured using the Seattle Angina Questionnaire at baseline
      (Time 1 [T1]) and 1 week before CA (Time 2 [T2]). The association between time on
      the waiting list and subjects' perceived anxiety was analyzed. RESULTS: Paired
      sample t tests comparing mean anxiety levels at T1 and T2 indicated a
      statistically significant increase in anxiety levels at T2 that did not seem to
      be related to the waiting time for CA (P =.000). Comparison of mean Seattle
      Angina Questionnaire scores at T1 and T2 indicated a trend toward deterioration
      in HRQL over time. CONCLUSIONS: Waiting for elective CA may have a negative
      impact on patients' psychologic status and HRQL. Nursing and clinical
      interventions to reduce anxiety and improve HRQL are indicated for this
      population.

PMID- 15252415
TI  - The effect of a tailored message intervention on heart failure readmission rates,
      quality of life, and benefit and barrier beliefs in persons with heart failure.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of a tailored
      message intervention on heart failure readmission rates, quality of life, and
      health beliefs in persons with heart failure (HF). DESIGN: This randomized
      control trial provided a tailored message intervention during hospitalization and
      1 week and 1 month after discharge.Theoretic framework The organizing framework
      was the Health Belief Model. SUBJECTS: Seventy persons with a primary diagnosis
      of chronic HF were included in the study. RESULTS: HF readmission rates and
      quality of life did not significantly differ between the treatment and control
      groups. Health beliefs, except for benefits of medications, significantly changed
      from baseline in the treatment group in directions posited by the Health Belief
      Model. CONCLUSIONS: A tailored message intervention changed the beliefs of the
      person with HF in regard to the benefits and barriers of taking medications,
      following a sodium-restricted diet, and self-monitoring for signs of fluid
      overload. Future research is needed to explore the effect of health belief
      changes on actual self-care behaviors.

PMID- 15252416
TI  - Pneumocystis carinii pneumonia in a non-HIV patient on steroids.

PMID- 15252417
TI  - Clostridium difficile and acute respiratory distress syndrome.

PMID- 15252418
TI  - Double coupling.

PMID- 15252420
TI  - Handling missing values in population data: consequences for maximum likelihood
      estimation of haplotype frequencies.
AB  - Haplotype frequency estimation in population data is an important problem in
      genetics and different methods including expectation maximisation (EM) methods
      have been proposed. The statistical properties of EM methods have been
      extensively assessed for data sets with no missing values. When numerous markers
      and/or individuals are tested, however, it is likely that some genotypes will be
      missing. Thus, it is of interest to investigate the behaviour of the method in
      the presence of incomplete genotype observations. We propose an extension of the
      EM method to handle missing genotypes, and we compare it with commonly used
      methods (such as ignoring individuals with incomplete genotype information or
      treating a missing allele as any other allele). Simulations were performed,
      starting from data sets of haematopoietic stem cell donors genotyped at three HLA
      loci. We deleted some data to create incomplete genotype observations in various
      proportions. We then compared the haplotype frequencies obtained on these
      incomplete data sets using the different methods to those obtained on the
      complete data. We found that the method proposed here provides better
      estimations, both qualitatively and quantitatively, but increases the computation
      time required. We discuss the influence of missing values on the algorithm's
      efficiency and the advantages and disadvantages of deleting incomplete genotypes.
      We propose guidelines for missing data handling in routine analysis.

PMID- 15252421
TI  - Increasing children's fruit and vegetable consumption: a peer-modelling and
      rewards-based intervention.
AB  - OBJECTIVE: To evaluate a peer-modelling and rewards-based intervention designed
      to increase children's fruit and vegetable consumption. DESIGN: Over a 5-month
      period, children in an experimental and a control school were presented with
      fruit and vegetables at lunchtime. Children aged 5-7 y also received fruit at
      snacktime (mid-morning). The intervention was implemented in the experimental
      school and levels of fruit and vegetable consumption were measured at baseline,
      intervention and at 4-month follow-up. SETTING: Two inner-city London primary
      schools. SUBJECTS: In total, 749 children aged 5-11 y. INTERVENTION: Over 16 days
      children watched video adventures featuring heroic peers (the Food Dudes) who
      enjoy eating fruit and vegetables, and received small rewards for eating these
      foods themselves. After 16 days there were no videos and the rewards became more
      intermittent. MAIN OUTCOME MEASURES: Consumption was measured (i) at lunchtime
      using a five-point observation scale; (ii) at snacktime using a weighed measure;
      (iii) at home using parental recall. RESULTS: Compared to the control school,
      lunchtime consumption in the experimental school was substantially higher at
      intervention and follow-up than baseline (P<0.001), while snacktime consumption
      was higher at intervention than baseline (P<0.001). The lunchtime data showed
      particularly large increases among those who initially ate very little. There
      were also significant increases in fruit and vegetable consumption at home
      (P<0.05). CONCLUSIONS: The intervention was effective in bringing about
      substantial increases in children's consumption of fruit and vegetables.

PMID- 15252422
TI  - Prognostic significance of Subjective Global Assessment (SGA) in advanced
      colorectal cancer.
AB  - OBJECTIVE: To evaluate the prognostic significance of Subjective Global
      Assessment (SGA) in advanced colorectal cancer and create statistically distinct
      prognostic groups of colorectal cancer patients based on clinical and nutritional
      variables. DESIGN: A retrospective clinical epidemiologic study. SETTING: A
      private tertiary care American Cancer Center. SUBJECTS: In total, 234 colorectal
      cancer patients aged 29-82 y treated at Cancer Treatment Centers of America at
      Midwestern Regional Medical Center between January 1995 and March 2001.
      INTERVENTION: SGA Questionnaire. SGA A-well nourished; SGA B-moderately
      malnourished; and SGA C-severely malnourished. Malnutrition was defined as either
      SGA B or SGA C. RESULTS: The prevalence of malnutrition in this patient
      population, as determined by SGA, was 52% (113/217). The median survival of
      patients with SGA A was 12.8 months (95% CI; 9.1-16.5), those with SGA B was 8.8
      months (95% CI; 6.7-10.9) and those with SGA C was 6 months (95% CI; 3.9-8.1);
      the difference being statistically significant at P=0.0013. Regression tree
      analysis identified prior treatment history, lactate dehydrogenase (LDH) and SGA
      to be important predictors of survival for our patient cohort. Patients with no
      prior treatment history (newly diagnosed disease), low LDH scores, and SGA A had
      the best overall survival of 40.4 months (95% CI; 30.45-50.4), whereas patients
      with prior treatment history (progressive disease), high LDH scores, and SGA B/C
      had the worst overall survival of 4.5 months (95% CI; 2.22-6.76). CONCLUSION: The
      SGA provides useful prognostic information in patients with advanced colorectal
      cancer.

PMID- 15252423
TI  - Estimation of iron absorption in humans using compartmental modelling.
AB  - OBJECTIVE: To evaluate whether a compartmental model could estimate iron
      absorption as accurately as the well-validated technique of plasma area under the
      curve using labelled test meals. DESIGN: The study is a randomised cross
      sectional intervention. SETTING: The study was carried out at the Human Nutrition
      Unit at the Institute of Food Research, Norwich, UK. SUBJECTS: A total of nine
      female volunteers, aged 33+/-8 y. INTERVENTIONS: Volunteers were given an oral
      dose (approximately 5 mg) of Fe-57 as iron sulphate in an orange juice test drink
      and simultaneously infused Fe-58 (approximately 200 microg) as iron citrate over
      90 min. Multiple blood samples were taken for the following 6 h. The samples were
      analysed by mass spectrometry and iron absorption was estimated using a
      mathematical model based on the appearance of Fe isotopes in plasma and the area
      under the curve technique. RESULTS: The geometric mean (-1 s.d., +1 s.d.)
      absorption of the model estimate is 16% (9, 31) and the area under curve estimate
      is 18% (8, 29). CONCLUSIONS: Results indicate that a compartmental model can be
      used to estimate labelled iron absorption although it is unlikely that this new
      method will be used in favour of an existing one. Further studies are now needed
      with unlabelled iron to assess whether the technique could have application in
      the assessment of total (haem+nonhaem) iron absorption from food.

PMID- 15252425
TI  - Eighteen sensations after breast cancer surgery: a two-year comparison of
      sentinel lymph node biopsy and axillary lymph node dissection.
AB  - PURPOSE/OBJECTIVES: To evaluate the prevalence, severity, and level of distress
      of 18 sensations at baseline (3-15 days) and 24 months after breast cancer
      surgery and to compare sensations after sentinel lymph node biopsy (SLNB) with
      those after SLNB plus immediate or delayed axillary lymph node dissection (ALND).
      DESIGN: Prospective, descriptive. SETTING: Evelyn H. Lauder Ambulatory Breast
      Center at Memorial Sloan-Kettering Cancer Center in New York, NY. SAMPLE: 294
      women with breast cancer; 214 had undergone breast conserving therapy, and 80 had
      undergone total mastectomy; 197 had had SLNB, and 97 had had SLNB and ALND.
      METHODS: Patients completed the Breast Sensation Assessment Scale (BSAS) at
      baseline and 3, 6, 12, and 24 months after surgery. MAIN RESEARCH VARIABLES:
      Prevalence, severity, and level of distress of sensations in patients who had
      undergone breast cancer surgery. FINDINGS: Sensations were less prevalent,
      severe, and distressing in patients undergoing SLNB than those undergoing ALND.
      This difference appeared to be limited to those undergoing breast conserving
      therapy. Most sensations after SLNB and ALND, even if prevalent, were not very
      severe or distressing. Some sensations persisted as long as two years. These
      included tenderness after SLNB and numbness after ALND. Patients often reported
      phantom sensations after total mastectomy. CONCLUSIONS: Overall, prevalence,
      severity, and level of distress were lower after SLNB compared to ALND, but some
      morbidity existed after SLNB. Certain sensations remained prevalent in both
      groups for as long as 24 months. IMPLICATIONS FOR NURSING: Nurses can use
      information from this study to provide more accurate education and support to
      patients.

PMID- 15252426
TI  - Expressed desire for hastened death in seven patients living with advanced
      cancer: a phenomenologic inquiry.
AB  - PURPOSE/OBJECTIVES: To explore the meanings and uses of an expressed desire for
      hastened death in seven patients living with advanced cancer. DESIGN: A
      phenomenologic inquiry. SETTING: Urban cancer research center. SAMPLE: Terminally
      ill patients with cancer who had expressed a desire for hastened death. METHODS:
      A series of in-depth semistructured interviews were audiotaped, transcribed,
      coded, and organized into themes. FINDINGS: The expression of desire for hastened
      death had many meanings and uses and communicated the following: (a) a
      manifestation of the will to live, (b) a dying process so difficult that an early
      death was preferred, (c) an intolerable immediate situation, even if not
      specifically identified by a patient, required immediate action, (d) a hastened
      death could extract a patient from an unendurable and specific situation, (e)
      manifestation of the last control the dying can exert, (f) a way of drawing
      attention to "me as a unique individual," (g) a gesture of altruism, (h) an
      attempt at manipulation of the family to avoid abandonment, and (i) a despairing
      cry depicting the misery of the current situation. CONCLUSIONS: Expression of
      desire for hastened death has many meanings and uses and is a tool of
      communication. IMPLICATIONS FOR NURSING: Listening to the patient's story will
      help nurses understand what is being asked for through the expression of a desire
      for hastened death.

PMID- 15252427
TI  - Emergency department waiting times for patients with cancer with febrile
      neutropenia: a pilot study.
AB  - PURPOSE/OBJECTIVES: To determine the time frame for evaluation and treatment of
      adult patients with febrile neutropenia in the emergency department (ED). DESIGN:
      Prospective, descriptive survey. SETTING: ED in a large, urban, academic health
      center. SAMPLE: 19 patients with febrile neutropenia during 23 ED visits in eight
      months. METHODS: Demographic and treatment variables and durations of time were
      recorded from ED and medical records. FINDINGS: Patients had fevers a mean of 21
      hours (range = 1-72 hours) before seeking treatment. Median waiting time from ED
      admission to examination was 75 minutes, 210 minutes before antibiotics were
      given, and 5.5 hours to hospital admission. Patients with more comorbidities and
      more extensive cancer waited significantly longer than those at lower risk (p
      less than 0.002). CONCLUSIONS: Although the standard of care is to treat febrile
      neutropenia as an oncologic emergency, patients waited prolonged periods prior to
      receiving treatment. Studies are indicated to examine early intervention for
      febrile neutropenia and to determine whether early intervention improves clinical
      outcomes. IMPLICATIONS FOR NURSING: Nurses may repeat this study at other
      settings and with other populations of people with cancer. Other studies may
      provide evidence that clinical outcomes are dependent on rapid intervention for
      febrile neutropenia in the cancer population or evaluate the efficacy of
      education that oncology nurses deliver to people with cancer and febrile
      neutropenia.

PMID- 15252428
TI  - Evidence-based nursing practice to prevent infection in hospitalized neutropenic
      patients with cancer.
AB  - PURPOSE/OBJECTIVES: To review studies that have assessed the effectiveness of
      selected nursing interventions used in hospitals to prevent healthcare-associated
      infections in neutropenic patients with cancer. DATA SOURCES: Literature review
      of low microbial diets, protective clothing and environments, personal hygiene,
      and oral care in English-language articles from PubMed; the Cumulative Index of
      Nursing and Allied Health Literature; the National Guideline Clearinghouse, 1980
      June 2003; and Cochrane Database of Systematic Reviews. DATA SYNTHESIS: Few
      studies have demonstrated the effectiveness of low microbial food and water and
      protective environments and clothing in reducing infections in neutropenic
      patients with cancer, and hospitals vary in these practices. Skin antisepsis
      reduces microbial counts, but data regarding the effect on infections are
      lacking. Many studies were characterized by insufficient sample sizes or use of
      multiple interventions. CONCLUSIONS: Major gaps exist in empirical evidence
      regarding which nursing interventions might be helpful in preventing or
      controlling healthcare-associated infections in neutropenic patients.
      IMPLICATIONS FOR NURSING: Although the evidence base for clinical practices such
      as a low microbial diet, protective environments and clothing, and special skin
      antisepsis regimens is weak, some of these practices seem prudent and reasonable.
      Until further evidence is available, clinicians can use consensus guidelines and
      should assist in identifying clinical practices that require additional research.
      Ultimately, interventions with little or no demonstrated efficacy should be
      examined systematically or abandoned. Additional studies of sufficient sample
      size regarding nursing practices such as the role of protective environments,
      room placement, antiseptic bathing, and prevention and treatment of oral
      complications are indicated. Because of difficulties in randomization and risk
      stratification, rigorous observational studies often may be an acceptable
      alternative to clinical trials.

PMID- 15252429
TI  - Sleep-wake disturbances in people with cancer part I: an overview of sleep, sleep
      regulation, and effects of disease and treatment.
AB  - PURPOSE/OBJECTIVES: To provide an overview of normal sleep, describe common sleep
      disorders, and discuss underlying sleep regulatory processes and how cancer,
      cancer treatment, and associated patient responses may adversely affect sleep.
      DATA SOURCES: Published peer-reviewed articles and textbooks. DATA SYNTHESIS: The
      duration, structure, and timing of sleep have a profound impact on health, well
      being, and performance. Patients with cancer may be at risk for disturbances in
      sleeping and waking resulting from disease- and nondisease-related circumstances
      that interfere with normal sleep regulation, including demographic, lifestyle,
      psychological, and disease- and treatment-related factors. CONCLUSIONS: Patients
      with cancer are at high risk for sleep-wake disturbances. IMPLICATIONS FOR
      NURSING: An understanding of normal sleep, sleep pathology, and the factors that
      can precipitate sleep disturbance provides a context for nurses to interpret
      sleep complaints in their patients, evaluate responses to sleep-promoting
      interventions, and guide decision making regarding referrals.

PMID- 15252430
TI  - Sleep-wake disturbances in people with cancer part II: evaluating the evidence
      for clinical decision making.
AB  - PURPOSE/OBJECTIVES: To evaluate the quality of evidence on sleep-wake
      disturbances in people with cancer as a basis for clinical decision making and to
      discuss implications of the evidence for oncology clinicians, educators, and
      researchers. DATA SOURCES: Published, peer-reviewed articles. DATA SYNTHESIS:
      Members of the 2001 Oncology Nursing Society (ONS) Advanced Practice Nurse
      Retreat Evidence-Based Practice Sleep Working Group selected and evaluated data
      sources using criteria and processes outlined by ONS. CONCLUSIONS: The
      development of nursing science related to sleep-wake disturbances among people
      with cancer and the application of research findings to clinical decision making
      are limited by the quantity and quality of published evidence. IMPLICATIONS FOR
      NURSING: Clinicians are challenged to develop a plan of care that includes the
      assessment of sleep-wake disturbances and interventions to address them. Nurse
      educators are challenged to include sleep-wake content and skills to evaluate
      empirical data and interventions for sleep-wake disturbances in degree and
      continuing education curricula. Nurse researchers are challenged to specify
      consistent conceptual and operational definitions of key variables in sleep-wake
      models, use measurement instruments with evidence of reliability and validity,
      and design clinical trials to test interventions for sleep-wake disturbances
      among people with cancer.

PMID- 15252431
TI  - The attitudes and beliefs of oncology nurse practitioners regarding direct-to
      consumer advertising of prescription medications.
AB  - PURPOSE/OBJECTIVES: To obtain information about the knowledge and attitudes of
      oncology nurse practitioners (ONPs) concerning the effect of direct-to-consumer
      (DTC) advertising of prescription medications on prescribing patterns. DESIGN:
      Exploratory survey. SETTING: Oncology Nursing Society Nurse Practitioner Special
      Interest Group members in the United States. SAMPLE: 221 of 376 ONPs completed
      the survey (58%). METHODS: Researcher-developed 12-question postal survey. MAIN
      RESEARCH VARIABLES: Knowledge and attitudes of ONPs on DTC advertising effects on
      prescribing patterns. FINDINGS: The findings were similar to those of previous
      studies of physicians regarding the number of visits when patients requested DTC
      advertised medications. Major differences were the positive attitudes of ONPs
      toward potentially longer patient visits to explain and educate patients
      regarding medication requests based on DTC advertising and smaller percentages of
      ONPs who felt "pressured" to prescribe requested medications. CONCLUSIONS: ONPs
      have mixed opinions regarding the practice of DTC advertising but do not believe
      that they are influenced heavily by advertising with regard to prescriptive
      practices. ONPs consider patient encounters for education purposes as appropriate
      and include information about requested DTC-advertised medications in their
      approach to patient care. IMPLICATIONS FOR NURSING: This is an exploratory survey
      of a specialty group of ONPs. More research is needed to further explore the
      practice of DTC advertising and potential influences on the prescribing patterns
      of ONPs. DTC advertising of prescription medications is increasing; ONPs need to
      increase their knowledge base about the potential for influences of prescriptive
      practices.

PMID- 15252432
TI  - Knowledge of oral cancer risk factors among african americans: do nurses have a
      role?
AB  - PURPOSE/OBJECTIVES: To assess the knowledge of oral cancer risk factors among
      African Americans. DESIGN: Descriptive; guided by the Patient/Provider/System
      Theoretical Model for cancer screening. SETTING: Community-based primary care
      center in a southern state. SAMPLE: 141 African Americans. The majority was
      female, had a 12th grade education, and had an income less than 10,000 dollars;
      25% were smokers. METHODS: Participants were asked to identify whether each of 15
      factors (i.e., seven risk factors and eight nonrisk factors) increased risk for
      oral cancer. One point was added for each correct response; therefore, scores
      could range from 0-15 points. Demographic data were collected. MAIN RESEARCH
      VARIABLES: Knowledge of and misconceptions about oral cancer. FINDINGS: Only six
      participants correctly identified all of the risk factors. The majority
      recognized tobacco but was not as aware of the effects of the sun, alcohol, and
      diet. Many erroneously identified factors such as hot beverages, poor oral
      hygiene, spicy foods, dentures, and mouthwash as risk factors. Those with higher
      incomes and those who visited their dentists in the prior year had more knowledge
      of risk factors. No differences were found in knowledge based on age, gender,
      education, or smoking status. CONCLUSIONS: Some patients are less likely to
      routinely visit a dentist and are less knowledgeable about the risk factors for
      oral cancer. Many of these risk factors are modifiable; therefore, patients need
      to be aware of the risks and have access to effective strategies to reduce risk.
      IMPLICATIONS FOR NURSING: Assess risk factors, teach risk reduction, and correct
      misinformation. Refer patients to dental professionals. Develop community
      outreach to African American men at barbershops and fraternal organizations.

PMID- 15252433
TI  - Types of social support in African Americans with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the types of social support that African
      Americans use to cope with the experience of cancer. RESEARCH APPROACH:
      Qualitative study using a grounded theory approach. SETTING: Participants' homes
      in the southeastern United States. PARTICIPANTS: A purposeful sample of 13
      African American men (aged 61-79 years) treated for prostate cancer and 15
      African American women (aged 42-87 years) treated for breast cancer. Participants
      were selected according to key variables known to influence social support: age,
      gender, marital status, education, geographic region, and proximity to family.
      METHODOLOGIC APPROACH: Open-ended and semistructured interviews were conducted
      with each participant (N = 28). Participants were interviewed until informational
      redundancy was achieved. Constant comparison techniques were used to identify
      variations of social support within and across cases. MAIN RESEARCH VARIABLES:
      The experience of social support during diagnosis or treatment for cancer as well
      as post-treatment. FINDINGS: Participants used types of social support not
      currently emphasized in the literature. The emotional support of "presence" was
      reported most frequently. Instrumental support included not only current
      conceptualizations but also offers of prayers, assistance to continue religious
      practices, and assistance to maintain social roles. Informational support
      included what to expect and how to manage symptoms, interpret information, and
      validate information received. CONCLUSIONS: Findings suggest the need to
      reconceptualize social support for African Americans with cancer and to refine
      instruments to include these different manifestations of social support.
      IMPLICATIONS FOR NURSING: Researchers can use these findings in the design of
      culturally relevant questionnaires and interventions for this population.
      Clinicians can use knowledge of the types of social support valued among African
      American patients with cancer to develop more appropriate strategies to promote
      healthy outcomes for this population.

PMID- 15252434
TI  - The effect of breast cancer screening messages on knowledge, attitudes, perceived
      risk, and mammography screening of African American women in the rural South.
AB  - PURPOSE/OBJECTIVES: To determine the effect of three types of breast cancer
      screening messages (positive/upbeat, neutral/cognitive, and negative/fear) on
      knowledge, attitudes, perceived risk for breast cancer, and mammography screening
      of African American women. DESIGN: Repeated measures intervention. SETTING: Three
      rural counties in the South. SAMPLE: 450 African American women aged 45-65 who
      had not received a mammogram in the past 12 months. METHODS: Following completion
      of pretest knowledge and attitude surveys, the women participated in a 60-minute
      breast health intervention session that included watching one of three videos
      with varied affective tones (positive/upbeat, neutral/cognitive, negative/fear).
      Data on knowledge, attitudes, perceived risk for breast cancer, and mammography
      screening were collected before, after, and 12 months following the intervention.
      MAIN RESEARCH VARIABLES: Knowledge, attitudes, perceived risk for breast cancer,
      and mammography screening. FINDINGS: No significant difference was found among
      video groups on mammography screening and knowledge of and attitudes about breast
      cancer over the three measurement periods. CONCLUSIONS: The affective tone of the
      educational videos did not make a difference in mammogram screening, attitudes,
      and knowledge of breast cancer screening. More women received a mammogram 12
      months postintervention than prior to the intervention; however, the influence of
      the intervention on this outcome is uncertain. IMPLICATIONS FOR NURSING: Nurses
      and health communication experts should design interventions that foster positive
      attitudes, increase knowledge about breast cancer screening, and stimulate women
      to participate in breast cancer screening as outlined by the American Cancer
      Society. These interventions need to be done in the context of the cultural norms
      and the education levels of the target population.

PMID- 15252436
TI  - Group dream work: a holistic resource for oncology nurses.
AB  - PURPOSE/OBJECTIVES: To explore dream work as a possible means for nurses to
      increase self-understanding and problem solving in personal and professional
      life. DESIGN: Hermeneutic phenomenologic, descriptive, and interpretive. SETTING:
      A comprehensive cancer center in the southern United States. SAMPLE: Six nurses
      with a mean age of 40 and 1-10 years of oncology nursing experience. METHODS:
      Interviews, guided by descriptive and interpretive phenomenology, were conducted
      with nurses before and one and six months after they participated in eight weekly
      sessions of a group focused on dream work. Phenomenologic analysis was done on
      verbatim transcriptions of all interviews. FINDINGS: Nurses found value in
      participating in dream groups, including having more open discussions about
      feelings and death, managing difficult situations, and attending to patients in
      the present. CONCLUSIONS: The value of learning to attend to dreams may be subtle
      but has value to nurses. IMPLICATIONS FOR NURSING: Incorporating dream work is
      one holistic intervention that may be useful to improve job satisfaction,
      communication, and relationships in this time of nursing shortage.

PMID- 15252435
TI  - Improving cancer pain management by homecare nurses.
AB  - PURPOSE/OBJECTIVES: To demonstrate the effects of a program, directed at homecare
      nurses, of structured educational interventions on the management of pain and
      opioid-related side effects in homecare patients with cancer. DESIGN: A
      longitudinal multilevel, randomized, controlled clinical trial. SETTING:
      Midwestern region in the United States. SAMPLE: 202 nurses caring for patients
      with cancer recruited from homecare agencies. METHODS: The two-tiered educational
      program focused on basic and advanced pain management strategies, particularly in
      the area of pharmacologic options and assertive communication skills. Instruments
      used were the Nurses' Knowledge and Attitudes Survey Regarding Pain, the barriers
      questionnaire, perception of control over pain, and a demographic questionnaire.
      MAIN RESEARCH VARIABLES: Knowledge and attitudes about pain management, barriers
      to pain management, and perception of control over pain. FINDINGS: Nurses in the
      intervention group had a significant increase in their knowledge, a more positive
      attitude about pain management, fewer perceived barriers to pain management, and
      an increase in perceived control over pain compared to the nurses who did not
      receive the intervention. CONCLUSIONS: The educational program Power Over Pain
      has beneficial effects for homecare nurses caring for patients with cancer pain.
      IMPLICATIONS FOR NURSING: A need exists for homecare nurses to gain more insight
      into pain management strategies and enhance their advocacy skills to improve pain
      management for patients with cancer treated in the home.

PMID- 15252437
TI  - "Research to practice": a practical program to enhance the use of evidence-based
      practice at the unit level.
AB  - PURPOSE/OBJECTIVES: To assist clinical nurses in translating research into
      clinical practice. DATA SOURCES: City of Hope Quality-of-Life (QOL) Model to
      guide presentations and discussion, research utilization theories, and evidence
      based practice literature. DATA SYNTHESIS: Based on percentage of individual
      participant involvement, the four domains of QOL, and a knowledge survey.
      OUTCOMES: Attendance, discussion, QOL domain ranking, satisfaction, and pre- and
      postknowledge scores. Attendance averaged 13 individuals; average discussion
      participation was 54%. The psychological QOL domain was most important (58%), and
      discussion averaged a score of 3 (1 = slow to 5 = lively). A one-point increase
      (scale 1-5) measured a change in knowledge. CONCLUSIONS: The challenge for
      nursing assessment is to fully address patient issues in the psychological
      domain. IMPLICATIONS FOR NURSING: A practical program can be formulated to bring
      evidence-based practice to the clinical setting.

PMID- 15252438
TI  - Assessing the strength and integrity of an intervention.
AB  - PURPOSE/OBJECTIVES: To evaluate the strength and integrity of a pilot behavioral
      intervention designed to assist mothers with breast cancer and their children.
      RESEARCH APPROACH: A single-group analysis of the strength and integrity
      characteristics of an intervention developed for a pilot research study. SETTING:
      Homes of study participants in an urban area. PARTICIPANTS: Seven households with
      a mother and father and one household with a single mother. METHODOLOGIC
      APPROACH: Observer-reported checklists, audiorecorded intervention session data,
      and structured interview data obtained from study participants. MAIN RESEARCH
      VARIABLES: Strength of the intervention included dimensions such as the
      theoretical foundation, competence of the interventionist, and specificity to the
      breast cancer experience in the family. Intervention integrity consisted of
      adherence by the interventionist and participants to the intervention plan.
      FINDINGS: The strength of the intervention was determined to be an asset. Careful
      planning had included a framework, a defined set of scripted sessions, a
      competent interventionist, and content specific to the breast cancer experience.
      In regard to integrity, the protocol content was delivered as scripted.
      Improvements in the dosage and purity dimensions were found to be needed.
      Homework assignments and in-session skill-building approaches with the mothers
      were refined. CONCLUSIONS: An intervention can be examined carefully for strength
      and integrity with established criteria to determine improvements needed.
      INTERPRETATION: A clinical research protocol can be improved through an
      assessment of an intervention's strength and integrity.

PMID- 15252439
TI  - Asian/Pacific Islander American women: age and death rates during hospitalization
      for breast cancer.
AB  - PURPOSE/OBJECTIVES: To investigate whether differences in age and death rates
      exist between hospitalized Asian/Pacific Islander American (APIA) women and women
      of other racial groups. DESIGN: Secondary data analysis of a national data set.
      SETTING: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample,
      Release 6, was used to obtain hospitalization data on women with breast cancer
      based on racial status. A total of 20,507 hospitalization records met the study
      criteria. SAMPLE: All women who were hospitalized with a primary diagnosis of
      breast cancer, were older than 18, and did not die during hospitalization, plus
      all women who met the criteria stated above but died during hospitalization.
      METHODS: Secondary data analysis. Post hoc analysis was used to identify
      significant differences among racial groups. FINDINGS: Significant differences
      were found between APIA and Caucasian and Latino women. Significant differences
      based on race were found between subjects who had died during hospitalization. On
      average, APIA women were the youngest to die. CONCLUSIONS: APIA women with breast
      cancer were among the youngest women being hospitalized and the youngest to die
      during hospitalization. IMPLICATIONS FOR NURSING: Cultural awareness by nurses is
      critical when discussing methods for prevention and early detection of breast
      cancer with minority women. Targeting new immigrants is a priority for those who
      screen and educate women about detection and treatment of breast cancer.

PMID- 15252440
TI  - Herbs or natural products that decrease cancer growth part one of a four-part
      series.
AB  - PURPOSE/OBJECTIVES: To provide evidence-based research information about 31 herbs
      and natural products that have shown potential in early research to decrease
      cancer growth or as adjuncts with cancer treatment. DATA SOURCES: Names of herbs
      and natural products with potential to decrease cancer growth have been selected
      from listings in the Natural Medicines Comprehensive Database and Lawrence Review
      of Natural Products-Monograph System. Information about these herbs has been
      found in evidence-based studies cited in references. DATA SYNTHESIS: In
      preliminary studies, 31 herbs and natural products appear to have potential for
      cancer treatment. CONCLUSIONS: This preliminary evidence may be useful to
      healthcare professionals and patients with cancer. IMPLICATIONS FOR NURSING: The
      information in this article is designed to provide quick access for healthcare
      professionals working in clinical oncology. Oncology nurses who have this
      information can become resources for patients and other healthcare professionals.

PMID- 15252441
TI  - Subcellular localization of frizzled receptors, mediated by their cytoplasmic
      tails, regulates signaling pathway specificity.
AB  - The Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling
      specificities activating either the canonical Wnt/beta-catenin pathway or
      Fz/planar cell polarity (PCP) signaling in Drosophila. The regulation of
      signaling specificity remains largely obscure. We show that Fz1 and Fz2 have
      different subcellular localizations in imaginal disc epithelia, with Fz1
      localizing preferentially to apical junctional complexes, and Fz2 being evenly
      distributed basolaterally. The subcellular localization difference directly
      contributes to the signaling specificity outcome. Whereas apical localization
      favors Fz/PCP signaling, it interferes with canonical Wnt/beta-catenin signaling.
      Receptor localization is mediated by sequences in the cytoplasmic tail of Fz2
      that appear to block apical accumulation. Based on these data, we propose that
      subcellular Fz localization, through the association with other membrane
      proteins, is a critical aspect in regulating the signaling specificity within the
      Wnt/Fz signaling pathways.

PMID- 15252442
TI  - A chromosomal memory triggered by Xist regulates histone methylation in X
      inactivation.
AB  - We have elucidated the kinetics of histone methylation during X inactivation
      using an inducible Xist expression system in mouse embryonic stem (ES) cells.
      Previous reports showed that the ability of Xist to trigger silencing is
      restricted to an early window in ES cell differentiation. Here we show that this
      window is also important for establishing methylation patterns on the potential
      inactive X chromosome. By immunofluorescence and chromatin immunoprecipitation
      experiments we show that histone H3 lysine 27 trimethylation (H3K27m3) and H4
      lysine 20 monomethylation (H4K20m1) are associated with Xist expression in
      undifferentiated ES cells and mark the initiation of X inactivation. Both marks
      depend on Xist RNA localisation but are independent of silencing. Induction of
      Xist expression after the initiation window leads to a markedly reduced ability
      to induce H3K27m3, whereas expression before the restrictive time point allows
      efficient H3K27m3 establishment. Our data show that Xist expression early in ES
      cell differentiation establishes a chromosomal memory, which is maintained in the
      absence of silencing. One consequence of this memory is the ability to introduce
      H3K27m3 efficiently after the restrictive time point on the chromosome that has
      expressed Xist early. Our results suggest that this silencing-independent
      chromosomal memory has important implications for the maintenance of X
      inactivation, where previously self-perpetuating heterochromatin structures were
      viewed as the principal form of memory.

PMID- 15252444
TI  - Activation-induced cytidine deaminase initiates immunoglobulin gene conversion
      and hypermutation by a common intermediate.
AB  - Depending on the species and the lymphoid organ, activation-induced cytidine
      deaminase (AID) expression triggers diversification of the rearranged
      immunoglobulin (Ig) genes by pseudo V (psiV) gene- templated gene conversion or
      somatic hypermutation. To investigate how AID can alternatively induce
      recombination or hypermutation, psiV gene deletions were introduced into the
      rearranged light chain locus of the DT40 B-cell line. We show that the stepwise
      removal of the psiV donors not only reduces and eventually abolishes Ig gene
      conversion, but also activates AID-dependent Ig hypermutation. This strongly
      supports a model in which AID induces a common modification in the rearranged
      V(D)J segment, leading to a conversion tract in the presence of nearby donor
      sequences and to a point mutation in their absence.

PMID- 15252445
TI  - Human population density and extinction risk in the world's carnivores.
AB  - Understanding why some species are at high risk of extinction, while others
      remain relatively safe, is central to the development of a predictive
      conservation science. Recent studies have shown that a species' extinction risk
      may be determined by two types of factors: intrinsic biological traits and
      exposure to external anthropogenic threats. However, little is known about the
      relative and interacting effects of intrinsic and external variables on
      extinction risk. Using phylogenetic comparative methods, we show that extinction
      risk in the mammal order Carnivora is predicted more strongly by biology than
      exposure to high-density human populations. However, biology interacts with human
      population density to determine extinction risk: biological traits explain 80% of
      variation in risk for carnivore species with high levels of exposure to human
      populations, compared to 45% for carnivores generally. The results suggest that
      biology will become a more critical determinant of risk as human populations
      expand. We demonstrate how a model predicting extinction risk from biology can be
      combined with projected human population density to identify species likely to
      move most rapidly towards extinction by the year 2030. African viverrid species
      are particularly likely to become threatened, even though most are currently
      considered relatively safe. We suggest that a preemptive approach to species
      conservation is needed to identify and protect species that may not be threatened
      at present but may become so in the near future.

PMID- 15252443
TI  - Hairy transcriptional repression targets and cofactor recruitment in Drosophila.
AB  - Members of the widely conserved Hairy/Enhancer of split family of basic Helix
      Loop-Helix repressors are essential for proper Drosophila and vertebrate
      development and are misregulated in many cancers. While a major step forward in
      understanding the molecular mechanism(s) surrounding Hairy-mediated repression
      was made with the identification of Groucho, Drosophila C-terminal binding
      protein (dCtBP), and Drosophila silent information regulator 2 (dSir2) as Hairy
      transcriptional cofactors, the identity of Hairy target genes and the rules
      governing cofactor recruitment are relatively unknown. We have used the chromatin
      profiling method DamID to perform a global and systematic search for direct
      transcriptional targets for Drosophila Hairy and the genomic recruitment sites
      for three of its cofactors: Groucho, dCtBP, and dSir2. Each of the proteins was
      tethered to Escherichia coli DNA adenine methyltransferase, permitting
      methylation proximal to in vivo binding sites in both Drosophila Kc cells and
      early embryos. This approach identified 40 novel genomic targets for Hairy in Kc
      cells, as well as 155 loci recruiting Groucho, 107 loci recruiting dSir2, and
      wide genomic binding of dCtBP to 496 loci. We also adapted DamID profiling such
      that we could use tightly gated collections of embryos (2-6 h) and found 20 Hairy
      targets related to early embryogenesis. As expected of direct targets, all of the
      putative Hairy target genes tested show Hairy-dependent expression and have
      conserved consensus C-box-containing sequences that are directly bound by Hairy
      in vitro. The distribution of Hairy targets in both the Kc cell and embryo DamID
      experiments corresponds to Hairy binding sites in vivo on polytene chromosomes.
      Similarly, the distributions of loci recruiting each of Hairy's cofactors are
      detected as cofactor binding sites in vivo on polytene chromosomes. We have
      identified 59 putative transcriptional targets of Hairy. In addition to finding
      putative targets for Hairy in segmentation, we find groups of targets suggesting
      roles for Hairy in cell cycle, cell growth, and morphogenesis, processes that
      must be coordinately regulated with pattern formation. Examining the recruitment
      of Hairy's three characterized cofactors to their putative target genes revealed
      that cofactor recruitment is context-dependent. While Groucho is frequently
      considered to be the primary Hairy cofactor, we find here that it is associated
      with only a minority of Hairy targets. The majority of Hairy targets are
      associated with the presence of a combination of dCtBP and dSir2. Thus, the DamID
      chromatin profiling technique provides a systematic means of identifying
      transcriptional target genes and of obtaining a global view of cofactor
      recruitment requirements during development.

PMID- 15252446
TI  - HIV infection of naturally occurring and genetically reprogrammed human
      regulatory T-cells.
AB  - A T-cell subset, defined as CD4(+)CD25(hi) (regulatory T-cells [Treg cells]), was
      recently shown to suppress T-cell activation. We demonstrate that human Treg
      cells isolated from healthy donors express the HIV-coreceptor CCR5 and are highly
      susceptible to HIV infection and replication. Because Treg cells are present in
      very few numbers and are difficult to expand in vitro, we genetically modified
      conventional human T-cells to generate Treg cells in vitro by ectopic expression
      of FoxP3, a transcription factor associated with reprogramming T-cells into a
      Treg subset. Overexpression of FoxP3 in naive human CD4(+) T-cells recapitulated
      the hyporesponsiveness and suppressive function of naturally occurring Treg
      cells. However, FoxP3 was less efficient in reprogramming memory T-cell subset
      into regulatory cells. In addition, FoxP3-transduced T-cells also became more
      susceptible to HIV infection. Remarkably, a portion of HIV-positive individuals
      with a low percentage of CD4(+) and higher levels of activated T-cells have
      greatly reduced levels of FoxP3(+)CD4(+)CD25(hi) T-cells, suggesting disruption
      of the Treg cells during HIV infection. Targeting and disruption of the T-cell
      regulatory system by HIV may contribute to hyperactivation of conventional T
      cells, a characteristic of HIV disease progression. Moreover, the ability to
      reprogram human T-cells into Treg cells in vitro will greatly aid in decoding
      their mechanism of suppression, their enhanced susceptibility to HIV infection,
      and the unique markers expressed by this subset.

PMID- 15252449
TI  - Gene duplication: the genomic trade in spare parts.

PMID- 15252453
TI  - Talking science.

PMID- 15252450
TI  - Lineage-specific gene duplication and loss in human and great ape evolution.
AB  - Given that gene duplication is a major driving force of evolutionary change and
      the key mechanism underlying the emergence of new genes and biological processes,
      this study sought to use a novel genome-wide approach to identify genes that have
      undergone lineage-specific duplications or contractions among several hominoid
      lineages. Interspecies cDNA array-based comparative genomic hybridization was
      used to individually compare copy number variation for 39,711 cDNAs, representing
      29,619 human genes, across five hominoid species, including human. We identified
      1,005 genes, either as isolated genes or in clusters positionally biased toward
      rearrangement-prone genomic regions, that produced relative hybridization signals
      unique to one or more of the hominoid lineages. Measured as a function of the
      evolutionary age of each lineage, genes showing copy number expansions were most
      pronounced in human (134) and include a number of genes thought to be involved in
      the structure and function of the brain. This work represents, to our knowledge,
      the first genome-wide gene-based survey of gene duplication across hominoid
      species. The genes identified here likely represent a significant majority of the
      major gene copy number changes that have occurred over the past 15 million years
      of human and great ape evolution and are likely to underlie some of the key
      phenotypic characteristics that distinguish these species.

PMID- 15252454
TI  - Honeybee odometry: performance in varying natural terrain.
AB  - Recent studies have shown that honeybees flying through short, narrow tunnels
      with visually textured walls perform waggle dances that indicate a much greater
      flight distance than that actually flown. These studies suggest that the bee's
      "odometer" is driven by the optic flow (image motion) that is experienced during
      flight. One might therefore expect that, when bees fly to a food source through a
      varying outdoor landscape, their waggle dances would depend upon the nature of
      the terrain experienced en route. We trained honeybees to visit feeders
      positioned along two routes, each 580 m long. One route was exclusively over
      land. The other was initially over land, then over water and, finally, again over
      land. Flight over water resulted in a significantly flatter slope of the waggle
      duration versus distance regression, compared to flight over land. The mean
      visual contrast of the scenes was significantly greater over land than over
      water. The results reveal that, in outdoor flight, the honeybee's odometer does
      not run at a constant rate; rather, the rate depends upon the properties of the
      terrain. The bee's perception of distance flown is therefore not absolute, but
      scene-dependent. These findings raise important and interesting questions about
      how these animals navigate reliably.

PMID- 15252456
TI  - Stopping the rot.

PMID- 15252455
TI  - Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys
      gambelii).
AB  - Twice a year, normally diurnal songbirds engage in long-distance nocturnal
      migrations between their wintering and breeding grounds. If and how songbirds
      sleep during these periods of increased activity has remained a mystery. We used
      a combination of electrophysiological recording and neurobehavioral testing to
      characterize seasonal changes in sleep and cognition in captive white-crowned
      sparrows (Zonotrichia leucophrys gambelii) across nonmigratory and migratory
      seasons. Compared to sparrows in a nonmigratory state, migratory sparrows spent
      approximately two-thirds less time sleeping. Despite reducing sleep during
      migration, accuracy and responding on a repeated-acquisition task remained at a
      high level in sparrows in a migratory state. This resistance to sleep loss during
      the prolonged migratory season is in direct contrast to the decline in accuracy
      and responding observed following as little as one night of experimenter-induced
      sleep restriction in the same birds during the nonmigratory season. Our results
      suggest that despite being adversely affected by sleep loss during the
      nonmigratory season, songbirds exhibit an unprecedented capacity to reduce sleep
      during migration for long periods of time without associated deficits in
      cognitive function. Understanding the mechanisms that mediate migratory
      sleeplessness may provide insights into the etiology of changes in sleep and
      behavior in seasonal mood disorders, as well as into the functions of sleep
      itself.

PMID- 15252457
TI  - Doing science in uncertain times.

PMID- 15252458
TI  - Nanotubes make big science.

PMID- 15252459
TI  - Dances as windows into insect perception.

PMID- 15252465
TI  - Whose copy? Whose rights?

PMID- 15252462
TI  - Translating DNA into synthetic molecules.

PMID- 15252468
TI  - Aqueous solution chemistry of [Mo3CuSe4]n+ (n = 4, 5) and [W3CuQ4]5+ (Q = S, Se)
      clusters.
AB  - The triangular cluster [Mo3Se4(H2O)9]4+ reacts with Cu turnings to give a new
      heterometallic cuboidal cluster [Mo3CuSe4(H2O)10]4+(purple; UV/Vis
      lambda(epsilon): 352(3907), 509(2613)). The reaction of [Mo3Se4(H2O)9]4+ with
      CuCl afforded the 5+ cube [Mo3CuSe4(H2O)10]5+(red; UV/Vis lambda(epsilon):
      356(5406), 500(3477)). In contrast, [W3Se4(H2O)9]4+ both with Cu and CuCl gives
      the 5+ cube, [W3CuSe4(H2O)10]5+(yellow-green; UV/Vis lambda(epsilon): 312(5327),
      419(3256) and 628(680)). Cyclic voltammetry of [M3CuQ4(H2O)10]5+ in 2 M HCl (M =
      Mo, W; Q = S, Se) shows a reversible one-electron reduction wave for the Mo
      clusters, but no reduction occurs for the W clusters prior to H+ reduction. In
      HCl solutions, Cl is coordinated to the Cu site of the clusters, alongside some
      less extensive coordination to Mo and W, and for [W3(CuCl)S4(H2O)6Cl3]+, isolated
      as the supramolecular adduct with cucurbit[6]uril, [W3(CuCl)S4(H2O)6Cl3]2Cl2 x
      C36H36N24O12 x 12H2O, the crystal structure was determined (Cu-W 2.856(4)
      angstroms, W-W 2.7432(15) angstroms, Cu-Cl 2.167(13) angstroms).

PMID- 15252469
TI  - The building block approach to extended solids: 3,5-pyrazoledicarboxylate
      coordination compounds of increasing dimensionality.
AB  - A series of M(II) complexes with the ligand 3,5-pyrazoledicarboxylic acid (H3dcp)
      has been synthesised mainly via hydrothermal reactions and their structures have
      been characterised. Simple mononuclear [Ni(Hdcp)(H2O)4] (1), Na2(mu
      H2O)2(H2O)8[Ni(Hdcp)2(H2O)2] (2), [M(H2dcp)2(H2O)2] x 2H2O [M = Co (3), Zn (4)
      and Cu (5)] and dinuclear (Et3NH)2[Cu2(dcp)2(H2O)2] (9) building blocks have been
      isolated and subsequently linked into 1-D chains [Mn(Hdcp)(H2O)2]infinity (6),
      [[Mn(H2O)4][Mn(Hdcp)2(H2O)2] x 4H2O]infinity (7), [Ni2(Hdcp)2(mu
      H2O)2(H2O)2]infinity (8), [[Ni(H2O)4][Ni2(dcp)2(H2O)4]]infinity (11), or 3-D
      arrays [[Na2(mu-H2O)2][Cu2(dcp)2]]infinity (10), [Cu3(dcp)2(H2O)4]infinity (12),
      utilising novel bridging modes of the H3dcp ligand. In the unprecedented 1-D
      Ni(II) chain 8, rarely reported double aqua-bridges link the Ni(II) ions to form
      an inter-linked double stranded chain. The magnetic properties of these compounds
      have been measured and reveal a variety of antiferromagnetic coupling behaviours
      induced by the ligand bridging modes.

PMID- 15252470
TI  - New pyridine carboxamide ligands and their complexation to copper(II). X-Ray
      crystal structures of mono-, di, tri- and tetranuclear copper complexes.
AB  - Seven new pyridine dicarboxamide ligands H2L(1-7) have been synthesised from
      condensation reactions involving pyridine-2,6-dicarboxylic acid (H2dipic),
      pyridine-2,6-dicarbonyl dichloride or 2,6-diaminopyridine with heterocyclic amine
      or carboxylic acid precursors. Crystallographic analyses of N,N'-bis(2
      pyridyl)pyridine-2,6-dicarboxamide monohydrate (H2L8 x H2O), N,N'-bis[2-(2
      pyridyl)methyl]pyridine-2,6-dicarboxamide and N,N'-bis[2-(2
      pyridyl)ethyl]pyridine-2,6-dicarboxamide monohydrate revealed extensive
      intramolecular hydrogen bonding interactions. 2,6-Bis(pyrazine-2
      carboxamido)pyridine (H2L6) and 2,6-bis(pyridine-2-carboxamido)pyridine (H2L7)
      reacted with copper(II) acetate monohydrate to give tricopper(II) complexes
      [Cu3(L)2(mu2-OAc)2]. X-Ray crystallography confirmed deprotonation of the amidic
      nitrogen atoms and that the (L6,7)2- ligands and acetate anions hold three
      copper(II) ions in approximately linear fashion. H2L8. Reacted with copper(II)
      tetrakis(pyridine) perchlorate to give [Cu(L8)(OH2)]2 x 2H2O, in which (L8)2- was
      tridentate through the nitrogen atoms of the central pyridine ring and the
      deprotonated carboxamide groups at one copper centre, with one of the terminal
      pyridyl rings coordinating to the other copper atom in the dimer. The
      corresponding reaction using H2L7 gave [Cu3(L7)2(py)2][ClO4]2, which transformed
      during an attempted recrystallisation from ethanol under aerobic conditions to a
      tetracopper(II) complex [Cu4(L7)2(L7-O)2].

PMID- 15252471
TI  - Substrate selectivity and conformational space available to bromoxynil and
      acrylonitrile in iron nitrile hydratase.
AB  - Nitrile hydratase (NHase) is used in the commercial conversion of acrylonitrile
      to acrylamide. There are two main types of NHase: the iron containing and the
      cobalt containing NHase. They catalyze the conversion of a wide variety of
      nitriles to their corresponding amides. The Co-NHases are more robust and have
      wider substrate specificity than the Fe-NHase. We have used dihedral and
      positional variational Monte Carlo conformational searches to determine the
      conformational space available to acrylonitrile and bromoxynil bound to the iron
      in the active site of NHase. Dioxane is an Fe-NHase inhibitor, but has no effect
      on Co-NHase activity. Our conformational searches showed that although the
      dioxane restricts the conformational freedom of the iron coordinated
      acrylonitrile, there is enough room in the active site for both the acrylonitrile
      and dioxane. A conformational search of dioxane in the active site of Fe-NHase,
      in the absence of a substrate, revealed that the acrylonitrile and dioxane do not
      share the same space. We have also shown that if the function of the metal ions
      in NHases is to activate the nitrile by binding to it and acting as a Lewis acid,
      then the entrance and channel residues are most likely responsible for Fe-NHase's
      inability to hydrolize bromoxynil.

PMID- 15252472
TI  - Hydrophobic vitamin B12. Part 19: electroorganic reaction of DDT mediated by
      hydrophobic vitamin B12.
AB  - The controlled-potential electrolysis of 1,1-bis(4-chlorophenyl)-2,2,2
      trichloroethane (DDT) was carried out at -1.4 V vs. Ag-AgCl in the presence of a
      hydrophobic vitamin B12, heptamethyl cobyrinate perchlorate. DDT was
      dechlorinated to form 1,1-bis(4-chlorophenyl)-2,2-dichloroethane (DDD), 1,1-bis(4
      chlorophenyl)-2,2-dichloroethylene (DDE), 1-chloro-2,2-bis(4
      chlorophenyl)ethylene (DDMU) and 1,1,4,4-tetrakis(4-chlorophenyl)-2,3-dichloro-2
      butene (TTDB)(E/Z), and quantitative recovery of the catalyst after the
      electrolysis was confirmed by electronic spectroscopy. A photo-sensitive
      intermediate having a cobalt-carbon bond formed during the electrolysis was
      characterized by electronic spectroscopy. A mechanism for the formation of
      various dechlorinated products was investigated by using deuterium solvents and
      various spectroscopic measurements such as UV-VIS and the EPR spin-trapping
      technique.

PMID- 15252473
TI  - Pyridylpyrrolides as alternatives to cyclometalated phenylpyridine ligands:
      synthesis and characterization of luminescent zinc and boron pyridylpyrrolide
      complexes.
AB  - The synthesis, structure, and properties of six luminescent pyridylpyrrolide
      complexes and the first structural characterization of pyridylpyrrolide metal
      complexes are reported. A series of new zinc complexes, bis(pyridylpyrrolyl)zinc,
      (R2PyrPy)2Zn (R = Me, Et, iPr, tBu, and Ph), that vary in their substituents on
      the pyrrole ring (Me, Et, iPr, tBu, and Ph), were prepared. Pyrrole substitution
      produced small structural changes in the complexes and affected the fluorescence
      properties very little. The zinc complexes were found to be luminescent, emitting
      at 495 nm (Phi = 0.32, 0.32 0.31, 0.19 and 0.57, respectively). A boron analog,
      (Me2PyrPy)BF2, was prepared and was found to share the luminescent properties
      with the zinc complexes, emitting at 505 nm (Phi = 0.22), but not their water
      sensitivity. A total of four crystal structures are reported, tBu2PyrPyH,
      (Me2PyrPy)2Zn, (tBu2PyrPy)2Zn, and (Me2PyrPy)BF2. tBu2PyrPyH crystallizes as a
      doubly hydrogen bonded dimer with non-coplanar pyridine and pyrrole rings. The
      solid-state structures of (Me2PyrPy)2Zn and (tBu2PyrPy)2Zn revealed that despite
      the large change in steric bulk, the two compounds have very similar structures.
      The structure of (Me2PyrPy)BF2 showed changes that are expected with the
      interaction between a smaller atom (B as compared to Zn). Molecular orbital
      calculations were performed on Me2PyrPyH, (Me2PyrPy)BF2, and (Me2PyrPy)2Zn using
      Gaussian 98 methods. It was found that the main transition (HOMO-LUMO) for all
      three molecules is a pi-->pi* transition and that in the inorganic complexes, the
      metal atom (zinc or boron) present has very little effect on transition, evidence
      that the optical properties are largely ligand based and that the B or Zn atom's
      main effect is lowering of the LUMO relative energy.

PMID- 15252474
TI  - Reactions of cationic iron clusters with ammonia, models of nitrogen
      hydrogenation and dehydrogenation.
AB  - The gas phase reactivities of small cationic iron clusters, Fen+ (n = 1-20),
      towards ammonia were investigated using Fourier transform ion cyclotron resonance
      (FT-ICR) mass spectrometry. Sequential addition of ammonia molecules to the
      clusters was observed to be the dominating process for n > 4. In the case of n =
      4 we observed addition of ammonia accompanied by dehydrogenation. This reaction
      was modelled using hybrid density functional theory. Clusters with n < 4 do not
      react with ammonia. Clusters Fen+ (n = 1-20) react with neither N2 nor H2 at
      around 10(-8) mbar. When dinitrogen was seeded into the expanding helium, mixed
      clusters of the type FenNm+ were observed. These ions react with H2, either by
      addition, or by substitution of N2. The clusters with m = 1 were isolated in
      separate experiments and reacted with H2, which showed that mixed clusters with n
      = 5-13 add up to 5 molecules of dihydrogen in successive slow reactions.

PMID- 15252475
TI  - Supramolecular triangular and linear arrays of metal-radical solids using
      pyrazolato-silver(I) motifs.
AB  - New chelating radical ligands pzNNH, pzINH, and pzbisINH (3-pyrazolyl nitronyl
      nitroxide, 3-pyrazolyl imino nitroxide, and pyrazole-3,5-diyl bis(imino
      nitroxide), respectively) were prepared. Complexation of these ligands with Ag+
      gave [Ag(pzNN)]n, [Ag(pzIN)]6, and [Ag(pzbisIN)]n containing the corresponding
      anionic forms of the ligands. From the X-ray crystal structure analysis,
      [Ag(pzIN)]6 was characterized as a dimer of almost planar triangular moieties
      where the pyrazolate worked as a bridge, and metal-metal bonds brought about
      dimerization of triangles. [Ag(pzbisIN)]n was characterized as a uniform zigzag
      chain consisting of pyrazolate bridges and Ag ions with a cis-Npz-Ag-Npz
      coordination structure. Antiferromagnetic interactions observed could be analyzed
      based on the structures determined for both compounds. Ferromagnetic coupling was
      observed in [Ag(pzNN)]n, and a polymeric structure was assumed although the
      crystal structure could not be determined. Novel supramolecular architectures
      using pyrazolate-substituted imino nitroxides have been developed, using the
      unique coordinative versatility of the pyrazolate derivatives

PMID- 15252476
TI  - Redistribution and fluxionality in heteropolyoxoperoxo complexes: [PO4[M2O2(mu
      O2)2(O2)2]2]3- with M = Mo and/or W.
AB  - When peroxotetramolybdophosphate, [(n-C4H9)4N]3[PO4[Mo2O2(mu-O2)2(O2)2]2],
      denoted (NBu4)3PMo4, and its tungsten(VI) analogue, (NBu4)3PW4, are mixed in
      acetonitrile at room temperature, redistribution occurs with the formation of
      three mixed-addenda species [PO4[Mo4-xWxO20]]3- (x = 1-3). The temperature
      dependence of the phosphorus-31 NMR spectra of a 1 1 mixture and of the pure
      salts, (NBu4)3PMo4 or (NBu4)3PW4, shows that [MO(O2)2] species are in chemical
      exchange, as are the [MOp] units of certain heteropolyacids (e.g. H3[PMo12O40] x
      aq and H3[PW12O40] x aq). However, there is no chemical exchange between free
      phosphate and [MO(O2)2] species in these systems; but there is fluxional
      behaviour involving PMo2W2, PMo4 and PW4. This is attributed to the rapid
      equilibrium between isomers (PMo2W2) and to equilibrium between anionic
      structures with tridentate (mu-eta2:eta1-O22-) and bidentate (eta2-O22-) modes of
      coordination for the two peroxo groups of the [M2O2(mu-O2)2(O2)2] moieties.

PMID- 15252477
TI  - Mixed crystals containing the dioxo complex [[Ph3SiO]2VO2]- and novel
      pentacoordinated oxoperoxo complex [[Ph3SiO]2VO(O2)]-: X-ray crystal structure
      and assessment as oxidation catalysts.
AB  - [n-Bu4N][[Ph3SiO]2VO2] reacts with H2O2 to yield an oxoperoxo complex which
      crystallizes as a mixed-crystal compound, [P(C6H5)4][[(C6H5)3 SiO]2VO2]x[[(C6H5)3
      SiO]2VO(O2)](1-x), 1(x = 0.57). It has been characterized by elemental analysis
      and spectroscopy (51V NMR, UV-visible and IR). The X-ray structure analysis
      reveals the presence of two interrelated anions: [[Ph3SiO]2VVO2]-, 1a, and
      [[Ph3SiO]2VVO(O2)]-, 1b with a cisoid geometry of the [VO(O2)]+ moiety. The two
      structures differ only slightly: anion 1a exhibits unusual tetrahedral
      coordination around the vanadium centre found in the precursor, whereas the
      geometry at the metal ion in 1b can be described as a trapezoidal pyramid. Steric
      constraints due to Ph3SiO- ligands and PPh4+ cations are responsible for this
      geometry. The reactivity of 1 in the C-C bond cleavage of 2-methylcyclohexanone
      under anaerobic conditions has been studied. The results suggest that peroxygen
      species are involved in the oxidative cleavage of C-C bonds of cycloalkanones.

PMID- 15252478
TI  - Electrochemical anion recognition with ferrocene functionalised macrocycles.
AB  - The syntheses and characterization of two new redox active cyclam ligands
      ferrocenylmethyl-(6-methyl-1,4,8,11-tetraazacyclotetradec-6-yl)-amine (L3) and
      1,1'-ferrocenylmethyl-bis(6-methyl-1,4,8,11-tetraazacyclotetradec-6-yl)-amine
      (L4) are reported. The compounds each possess a ferrocenyl group bearing one (L3)
      or two (L4) appended macrocycles linked by their exocyclic amino groups and the
      crystal structures of both compounds have been determined. Anion binding of L3
      and L4 was investigated by electrochemical titrations where H-bonding to each
      macrocycle causing a shift in the Fc+/0 redox potential was used as a reporter of
      guest binding. The Zn(II) complex of L3 has also been isolated and characterized
      structurally. These compounds were analysed for their capacity to
      electrochemically recognize anions in both aqueous and non-aqueous solution. We
      have found that L3, L4 and [ZnL3]2+ sense Cl- and AcO- anions in MeCN-CH2Cl2, a
      function that is lost in aqueous solution.

PMID- 15252479
TI  - Synthesis, characterization and ethylene reactivity of 2
      diphenylphosphanylbenzamido nickel complexes.
AB  - Addition of primary amines to N-[2-(diphenylphosphanyl)benzoyloxy]succinimide
      affords 2-diphenylphosphanylbenzamides, Ph2PC6H4C(O)NHR (R = C(CH3)3, 3; R = H,
      4; R = CH2CH2CH3, 5; R = CH(CH3)2, 6). Addition of NiCl(eta3-CH2C6H5)(PMe3) to
      the deprotonated potassium salts of the amides and subsequent treatment of two
      equivalents of B(C6F5)3 to the resulting products furnishes eta3-benzyl
      zwitterionic nickel(II) complexes, [Ph2PC6H4C(O)NR-kappa2N,P]Ni(eta3-CH2C6H5) (R
      = C6H5, 9; R = C(CH3)3, 10; R = H, 11; R = CH2CH2CH3, 12; R = CH(CH3)2, 13).
      Solid structures of 9, 11, 13 and the intermediate eta1-benzyl nickel(II)
      complexes, [Ph2PC6H4C(O)NR-kappa2N,P]Ni(eta1-CH2C6H5)(PMe3) (R = C6H5, 7; R =
      C(CH3)3, 8) were determined by X-ray crystallography. When ethylene is added to
      the eta3-benzyl zwitterionic nickel(II) complexes, butene is obtained by the
      complexes 9-12 but complex 13 provides very high molecular-weight branched
      polyethylene (Mw, approximately 1300000) with excellent activity (up to 5200 kg
      mol-1 h-1 at 100 psi gauge).

PMID- 15252480
TI  - Insertion reactions of SO2 into Pd-OR bonds: preparation of alkyl sulfito
      complexes of palladium(II).
AB  - Mononuclear palladium-hydroxo complexes of the type [Pd(N-N)(C6F5)(OH)][(N-N =
      2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me2bipy), or N,N,N',N'
      tetramethylethylenediamine (tmeda) react with SO2(1 atm) at room temperature in
      alcohol (methanol, ethanol, propanol or isopropanol) to yield alkyl sulfito
      palladium complexes [Pd(N-N)(C6F5)(SO2OR)](R = Me, Et, Pr or iPr). Similar alkyl
      sulfito complexes [Pd(N-N)(C6F5)(SO2OR)](N-N = bis(3,5-dimethylpyrazol-1
      yl)methane); R = Me or Et) are obtained when [Pd(N-N)(C6F5)Cl] is treated with
      KOH in the corresponding alcohol ROH and SO2 is bubbled through the solution. The
      reaction of [Pd(bipy)(C6F5)(OH)] with SO2 in tetrahydrofuran gives [Pd(N
      N)(C6F5)(SO2OH)]. The X-ray diffraction study of [Pd(tmeda)(C6F5)(SO2OPr)] has
      established the sulfur coordination of the propyl sulfito ligand.

PMID- 15252481
TI  - Generation and trapping reaction of an efficient 1,2-dehydrocarborane precursor,
      phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate.
AB  - An efficient 1,2-dehydrocarborane precursor, phenyl[o
      (trimethylsilyl)carboranyl]iodonium acetate, was readily prepared by reaction of
      [o-(trimethylsilyl)carboranyl]lithium and IPh(OAc)2. The facile 2+4 cycloaddition
      of with dienes such as anthracene, naphthalene, norborna-2,5-diene and 2,5
      dimethylfuran gave high yields of the 1,2-dehydrocarborane adducts in the
      presence of a desilylating agent. The reaction of with a cyclic alkene and
      strained cycloalkynes afforded the adducts formed by the ene reaction and the 2+2
      cycloaddition reaction. The reaction of with a bicyclopalladacycle yielded the
      cyclization product. The structures of compounds and were determined by single
      crystal X-ray crystallography.

PMID- 15252482
TI  - Synthesis and structure of boron-bridged constrained geometry complexes of
      titanium.
AB  - The boron-bridged constrained geometry titanium complexes [Ti[eta5:eta1
      (C5H4)B(NR2)NPh](NMe2)2][R = iPr (3), SiMe3(4)] and [Ti[eta5:eta1
      (C9H6)B(NiPr2)NPh](NMe2)2](12) have been prepared in good yields by amine
      elimination reaction from [Ti(NMe2)4]. Subsequent deamination-chlorination with
      excess Me3SiCl yielded the corresponding dichloro-complexes (5, 6, 13). Reaction
      of the analogous ligand precursors (C5H5)B(NiPr2)N(H)R (R = Cy, tBu) with
      [Ti(NMe2)4] did not result in the expected bridged compounds, but rather in the
      half-sandwich complexes [Ti[(eta5-C5H4)B(NiPr2)N(H)R](NMe2)3][R = Cy (9), tBu
      (10)]. All compounds were fully characterised by means of multinuclear NMR
      spectroscopy. Thorough investigation of substituent effects was achieved by
      comparative X-ray diffraction studies on complexes 3, 5, 6 and 12.

PMID- 15252483
TI  - Novel lanthanide(II) complexes supported by carbon-bridged biphenolate ligands:
      synthesis, structure and catalytic activity.
AB  - [Ln[N(SiMe3)2]2(THF)2](Ln = Sm, Yb) reacts with 1 equiv. of carbon-bridged
      biphenols, 2,2'-methylene-bis(6-tert-butyl-4-methylphenol)(L1H2) or 2,2'
      ethylidene-bis(4,6-di-tert-butylphenol)(L2H2), in toluene to give the novel
      aryloxide lanthanide(II) complexes [[LnL1(THF)n]2](Ln = Sm, n = 3 (1); Ln = Yb, n
      = 2 (2)) and [[LnL2(THF)3]2](Ln = Sm (5); Ln = Yb (6)) in quantitative yield,
      respectively. Addition of 2 equiv. of hexamethylphosphoric triamide (HMPA) to a
      tetrahydrofuran (THF) solution of 1, 2 and 5 affords the corresponding HMPA
      coordinated complexes, [[LnL1(THF)m(HMPA)n]2(THF)y](Ln = Sm, n = 2, m = 0, y = 2
      (3); Ln = Yb, m = 1, n = 1, y = 6 (4)) and [[SmL2(HMPA)2]2](7) in excellent
      yields. The single-crystal structural analyses of 3, 4 and 7 revealed that these
      aryloxide lanthanide(II) complexes are dimeric with two Ln-O bridges. The
      coordination geometry of each lanthanide metal can be best described as a
      distorted trigonal bipyramid. Complexes 1-3, 5 and 7 can catalyze the ring
      opening polymerization of epsilon-caprolactone (epsilon-CL), and 1-3, along with
      5 show moderate activity for the ring-opening polymerization of 2,2
      dimethyltrimethylene carbonate (DTC) and the copolymerization of epsilon-CL and
      DTC to give random copolymers with high molecular weights and relatively narrow
      molecular weight distributions..

PMID- 15252484
TI  - Gold derivatives of scorpionates: comparison with the other coinage metal
      poly(pyrazolyl)borate analogues.
AB  - Gold derivatives [Au(Tpx)(PR3)](Tpx = Tp, hydrotris(pyrazol-1-yl)borate or Tp*,
      hydrotris(3,5-dimethylpyrazol-1-yl)borate; R = Ph or tBu) and
      [Au(pzTp)(PR3)x](pzTp = tetrakis(pyrazol-1-yl)borate, x = 1 or 2, R = Ph or tBu)
      have been synthesised and characterized both in solution (1H- and 31P[1H]-NMR)
      and in the solid state (IR, single crystal X-ray structure analysis, 31P CPMAS).
      31P [1H] NMR solution data suggest greater stability of the
      tetrakis(pyrazolyl)borate relative to those of tris(pyrazolyl)borate. All
      compounds are fluxional at room temperature. In order to compare [Au(Tp*)(PPh3)]
      with analogous coinage metal adducts we have synthesized and structurally
      characterized [Cu(Tp*)(PPh3)] x PPh3 and [Ag(Tp*)(PPh3)] x 2MeCN. In
      [Au(Tp*)(PPh3)] the gold atom adopts a distorted tetrahedral geometry with <Au-P>
      2.181(5) and <Au-N> 2.37(2) angstroms (cf. <Cu-P,N> 2.166(6), 2.098(1) in
      [Cu(Tp*)PPh3], 2.156(2), 2.075(7) in [Cu(Tp*)(PPh3)] x PPh3; and <Ag-P,N> in
      [Ag(Tp*)PPh3] x MeCN 2.347(12), 2.35(5) angstroms). There are three independent
      [Au(Tp*)(PPh3)] molecules in the asymmetric unit of the structure with their
      PAu...B axes lying on the cell diagonal of a cubic P213 cell, two with the same
      chirality aligned opposed in direction to the third which is of opposite
      chirality. A number of Cu, Ag and Au complexes containing scorpionate ligands
      have also been investigated by 31P cross-polarization magic-angle-spinning
      (CPMAS) NMR spectroscopy.

PMID- 15252485
TI  - Extending the coordination capabilities of tertiary phosphines and arsines:
      preparation, molecular structure, and reactivity of dinuclear rhodium complexes
      with PR3 and AsR3 in a doubly bridging coordination mode.
AB  - The reactions of [Rh2(kappa2-acac)2(mu-CPh2)2(mu-PR3)] (PR3= PMe34, PMe2Ph 7,
      PEt38) with an equimolar amount of Me3SiX (X = Cl, Br, I) afforded the
      unsymmetrical complexes [Rh2X(kappa2-acac)(mu-CPh2)2(mu-PR3)]5, 9-12, which
      contain the phosphine in a semi-bridging coordination mode. From 4 and excess
      Me3SiCl, the tetranuclear complex [[Rh2Cl(mu-Cl)(mu-CPh2)2(mu-PMe3)]2]6 was
      obtained. In contrast, the reaction of 4 with an excess of Me3SiX (X = Br, I)
      yielded the dinuclear complexes [Rh2X2(mu-CPh2)2(mu-PMe3)]13, 14 in which, as
      shown by the X-ray crystal structure analysis of 14, the bridging phosphine is
      coordinated in a truly symmetrical bonding mode. While related compounds with
      PEt3 and PMe2Ph as bridging ligands were prepared on a similar route, the complex
      [Rh2Cl2(mu-CPh2)2(mu-PiPr3)]19 was obtained from the mixed-valence species
      [(PiPr3)Rh(mu-CPh2)2Rh(kappa2-acac)2]17 and HCl. The reaction of [Rh2(kappa2
      acac)2(mu-CPh2)2(mu-SbiPr3)]3 with AsMe3 gave the related Rh(mu-AsMe3)Rh compound
      21. With Me3SiCl, the acac ligands of 21 can be replaced stepwise by chloride to
      give [Rh2Cl(kappa2-acac)(mu-CPh2)2(mu-AsMe3)]23 and [[Rh2Cl(mu-Cl)(mu-CPh2)2(mu
      AsMe3)]2]24, the latter being isomorphous to the phosphine-bridged dimer 6.

PMID- 15252486
TI  - Molecular structure of Hf(BH4)4 investigated by quantum mechanical calculations
      and gas-phase electron diffraction.
AB  - The structure of the gaseous hafnium tetrakis(tetrahydroborate) molecule,
      Hf(BH4)4, has been investigated by detailed quantum mechanical calculations and
      by analysis of its gas electron-diffraction (GED) pattern. The ground-state
      geometry possesses T symmetry with all of the triply-bridged BH4 groups twisted
      equally about the Hf...B-H axes. Salient structural parameters (ra distances, r
      angles) deduced from the GED pattern by the SARACEN method were: r(Hf...B)
      231.4(2), r(Hf-Hb) 221.5(7), r(B-Hb) 127.6(5), r(B-Ht) 121(1) pm, Hf...B-Hb
      69.4(3), Hb-B-Hb 108.4(4), Hb-B-Ht 110.6(3), B...Hf...B-Hb 166(1) degrees. A
      notable feature is the large magnitude of the Hf...B and Hf-Hb anharmonicity
      parameters, attributed to the fluxional hydrogen atom exchange process. The
      properties are compared with those of related tetrahydroborates..

PMID- 15252487
TI  - Self-assembly sodalite-like framework.
AB  - The dense packing of shape complementary N-donor molecules dominates the self
      assembly of coordination polymers possessing sodalite-like topology and supports
      nanosize molecular cages.

PMID- 15252488
TI  - Intramolecular nucleophilic activation promoting efficient hydrolytic cleavage of
      DNA by (aqua)bis(dipyridoquinoxaline)copper(II) complex.
AB  - The axial aqua bound copper(II) complex [Cu(dpq)2(H2O)](ClO4)2, having a planar
      NN-donor heterocyclic base dipyridoquinoxaline (dpq) as the DNA minor groove
      binder, shows efficient hydrolytic cleavage of supercoiled DNA in the dark and in
      the absence of any external reagents, as evidenced from T4 ligase experiments,
      with a rate of 5.58 +/- 0.4 h(-1) and a rate enhancement of 1.55 x 10(8).

PMID- 15252489
TI  - Complexes of 5,5'-aminoacido-substituted 2,2'-bipyridyl ligands: control of
      diastereoselectivity with a pH switch and a chloride-responsive combinatorial
      library.
AB  - The synthesis and coordination chemistry of a new chiral ligand, 2,2'-bipyridine
      substituted at the 5 and 5' positions by N-methyl-L-valine methyl ester (5), is
      presented. The ligand readily forms complexes [M(5)3]2+ where M = Co(II) and
      Fe(II) in CH3CN, and the complexation reaction is slightly diastereoselective
      (d.e. =ca. 20%) in favour of the Delta diastereomer. The addition of six
      equivalents of HCl to these complexes [M(II)(5)3]2+ leads to formation of Delta
      [M(II)(5H2)3]8+ with a d.e. of 100%. This high diastereoselectivity can be
      reversed by the addition of base i.e. the diastereoselectivity can be controlled
      by the pH. Delta-[Fe(5H2)3]8+ was found to bind chloride ions in CD3OD-CD3CN
      (6:1) with a binding constant of 260 M(-1). [Co(II)(5)3]2+ can be oxidised to
      Delta-[Co(III)(5H2)3]9+. Formation constants for both [Co(II)(5)3]2+ and
      [Co(II)(5H2)3]8+ in acetonitrile were obtained by spectrophotometric titrations.
      In the former case, the stability constant, log beta3 = 19.5(8), is very similar
      to that measured for [Co(II)(bipy)3]2+ (log beta3 = 19.3(7)) but this drops
      significantly when the amine groups of are protonated (log beta3 = 16.5(2)). A
      dynamic combinatorial library was prepared by mixing three equivalents of, three
      equivalents of bipy, and two equivalents of Co(II) in CD3CN. The presence of all
      possible Delta- and Lambda-[Co(II)(5)x(bipy)(3-x)]2+ complexes was inferred from
      1H NMR and ES-MS spectra. Addition of protons to this library reduced the number
      of components by inducing diastereoselectivity, and presence of chloride further
      simplified the 1H NMR spectrum, indicating that [Cl2 ligand Delta
      [Co(II)(5H2)3]]6+ and [Co(II)(bipy)3]2+ were the dominant products.

PMID- 15252490
TI  - Electrochemical and theoretical study of the redox properties of transition metal
      complexes with [Pt2S2] cores.
AB  - The oxidation processes undergone by the [Pt2(mu-S)2] core in
      [Pt2(P[intersection]P)2(mu-S)2](P[intersection]P = Ph2P(CH2)nPPh2, n= 2,3)
      complexes have been analysed on the basis of electrochemical measurements. The
      experimental results are indicative of two consecutive monoelectronic oxidations
      after which the [Pt2(mu-S)2] core evolves into [Pt2(mu-S2)]2+, containing a
      bridging disulfide ligand. However, the instability of the monoxidised
      [Pt2(P[intersection]P)2(mu-S)2]+ species formed initially, which converts into
      [Pt3(P[intersection]P)3(mu-S)2]2+, hampered the synthesis and characterisation of
      the mono and dioxidised species. These drawbacks have been surpassed by means of
      DFT calculations which have also allowed the elucidation of the structural
      features of the species obtained from the oxidation of [Pt2(P[intersection]P)2(mu
      S)2] compounds. The calculated redox potentials corresponding to the oxidation
      processes are consistent with the experimental data obtained. In addition,
      calculations on the thermodynamics of possible processes following the
      degradation of [Pt2(P[intersection]P)2(mu-S)2]+ are fully consistent with the
      concomitant formation of monometallic [Pt(P[intersection]P)S2)] and trimetallic
      [Pt3(P[intersection]P)3(mu-S)2]2+ compounds. Extension of the theoretical study
      on the [Pt2Te2] core and comparisons with the results obtained for [Pt2S2] have
      given a more general picture of the behaviour of [Pt2X2](X = chalcogenide) cores
      subject to oxidation processes.

PMID- 15252491
TI  - Synthesis, characterisation and molecular structure of Re(III) 2-oxacyclocarbenes
      stabilised by a benzoyldiazenido ligand.
AB  - A family of new Fischer-type rhenium(III) benzoyldiazenido-2-oxacyclocarbenes of
      formula [(ReCl2[eta1-N2C(O)Ph][=C(CH2)nCH(R)O](PPh3)2][n = 2, R = H (2), R = Me
      (3); n = 3, R = H (4), R = Me (5)] have been prepared by reaction of [ReCl2[eta2
      N2C(Ph)O](PPh3)2] (1) with omega-alkynols, such as 3-butyn-1-ol, 4-pentyn-1-ol, 4
      pentyn-2-ol, 5-hexyn-2-ol in refluxing THF. The correct formulation of the
      carbene derivatives 2-5 has been unambiguously determined in solution by NMR
      analysis and confirmed for compounds 2-4 by X-ray diffraction methods in the
      solid state. All complexes are octahedral with the benzoyldiazenido ligand,
      Re[N2C(O)Ph], adopting a "single bent" conformation. The coordination basal plane
      is completed by an oxacyclocarbene ligand and two chlorine atoms. Two
      triphenylphosphines in trans positions with respect to each other complete the
      octahedral geometry around rhenium. The reactivity of 1 towards different alkynes
      and alkenes including propargyl- and allylamine has been also studied. With
      propargyl amine, monosubstituted or bisubstituted complexes, [(ReCl2[eta1
      N2C(O)Ph][eta1-NH2CH2C triple bond CH]n(PPh3)(3-n)][n= 1 (6); n = 2 (7)], have
      been isolated depending on the reaction conditions. In contrast, the reaction
      with allylamine gave only the disubstituted complex [(ReCl2[eta1-N2C(O)Ph][eta1
      NH2CH2CH=CH2]2(PPh3)] (8). The molecular structure of the monosubstituted adduct
      has been confirmed by X-ray analysis in the solid state.

PMID- 15252492
TI  - Tuning facial-meridional isomerisation in monometallic nine-co-ordinate
      lanthanide complexes with unsymmetrical tridentate ligands.
AB  - The unsymmetrical tridentate benzimidazole-pyridine-carboxamide units in ligands
      L1-L4 react with trivalent lanthanides, Ln(III), to give the nine-co-ordinate
      triple-helical complexes [Ln(Li)3]3+ (i = 1-4) existing as mixtures of C3
      symmetrical facial and C1-symmetrical meridional isomers. Although the beta13
      formation constants are 3-4 orders of magnitude smaller for these complexes than
      those found for the D3-symmetrical analogues [Ln(Li)3]3+ (i = 5-6) with
      symmetrical ligands, their formation at the millimolar scale is quantitative and
      the emission quantum yield of [Eu(L2)3]3+ is significantly larger. The fac
      [Ln(Li)3]3+ <--> mer-[Ln(Li)3]3+ (i = 1-4) isomerisation process in acetonitrile
      is slow enough for Ln = Lu(III) to be quantified by 1H NMR below room
      temperature. The separation of enthalpic and entropic contributions shows that
      the distribution of the facial and meridional isomers can be tuned by the
      judicious peripheral substitution of the ligands affecting the interstrand
      interactions. Molecular mechanics (MM) calculations suggest that one
      supplementary interstrand pi-stacking interaction stabilises the meridional
      isomers, while the facial isomers benefit from more favourable electrostatic
      contributions. As a result of the mixture of facial and meridional isomers in
      solution, we were unable to obtain single crystals of 1:3 complexes, but the X
      ray crystal structures of their nine-co-ordinate precursors
      [Eu(L1)2(CF3SO3)2(H2O)](CF3SO3)(C3H5N)2(H2O) (6, C45H54EuF9N10O13S3, monoclinic,
      P2(1)/c, Z = 4) and [Eu(L4)2(CF3SO3)2(H2O)](CF3SO3)(C4H4O)(1.5) (7,
      C51H66EuF9N8O(15.5)S3, triclinic, P1, Z = 2) provide crucial structural
      information on the binding mode of the unsymmetrical tridentate ligands.

PMID- 15252493
TI  - The structural and spectroscopic characterisation of three actinyl complexes with
      coordinated and uncoordinated perrhenate: [UO2(ReO4)2(TPPO)3],
      [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2 and [NpO2(TPPO)4][ReO4].
AB  - The first structural characterization of an actinide complex with coordinated
      perrhenate is reported, [UO2(ReO4)2(TPPO)3] (1). In this [UO2]2+ complex two
      [ReO4]- anions and three TPPO (triphenylphosphine oxide) P=O donor ligands are
      coordinated in the equatorial plane in a cisoid arrangement. This bonding
      arrangement, and apparent strain observed in the equatorially bonded ligands, is
      attributed to the solid state packing in adjacent molecules in which hydrophobic
      TPPO ligands form an effective "shell" around a hydrophilic core of two
      UO2(ReO4)2 moieties. Solid state vibrational spectroscopy (infrared and Raman),
      31P CP MAS NMR and elemental analysis are also consistent with the formula of 1.
      Solution state vibrational spectroscopy and 31P NMR measurements in EtOH indicate
      the lability of the TPPO and [ReO4]- groups. The photolytic generation of
      peroxide in EtOH solutions of 1 leads to the formation of trace quantities of
      [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2, 2, in which the coordinated [ReO4]- groups of 1
      have been displaced by bridging O2(2-), derived from atmospheric O2. Finally,
      attempts to synthesise a [NpO2]+ analogue of have resulted only in the formation
      of [NpO2(TPPO)4][ReO4], 3, in which [ReO4]- acts solely as a counter anion. From
      these results it can be concluded that [ReO4]- will bond to [UO2]2+, but will be
      readily displaced by a more strongly coordinating ligand (e.g. peroxide) and will
      not coordinate to an actinyl cation with a lower charge, [NpO2]+, under the same
      reaction conditions.

PMID- 15252494
TI  - Thermodynamic and biodistribution studies of Zn(II), Ca(II), Gd(III) and Cu(II)
      complexes of 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime.
AB  - The thermodynamic equilibria of copper(II), zinc(II), calcium(II) and
      gadolinium(III) with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime
      (L1) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3).
      Copper and gadolinium form stable complexes with the ligand while the
      corresponding zinc species are more than 9 log units less stable. No complexes
      between calcium and the ligand were detected. The low binding strength of L1
      towards zinc is attributed to the square-planar coordination geometry forced on
      the metal ion by the ligand as revealed by molecular mechanics calculations and
      molecular dynamics simulations. Speciation calculations, using a computer model
      of blood plasma, indicate that, despite the high concentration of zinc(II) and
      calcium(II) in vivo, L1 is able to increase the low-molecular-mass fraction of
      copper in plasma. Octanol/water partition coefficient of [CuL1H(-1)] indicates
      that although this species is largely hydrophilic, approximately 6% of the
      complex goes into the octanol phase and hence may promote dermal absorption of
      copper by the same amount. The dermal penetration rate is calculated to be 4.0 x
      10(-4) mm h(-1). The [CuL1H(-1)] complex, which predominates at pH 7.4, is a poor
      mimic of native copper-zinc superoxide dismutase. Biodistribution experiments
      using the 64Cu-labelled [CuL1H(-1)] complex indicate an initial high uptake of
      this species in the liver followed by redistribution into muscle. Only a small
      amount is excreted through the urine.

PMID- 15252495
TI  - [(mu-L)[RuII(acac)2]2]n, n= 2+, +, 0, -, 2-, with L = 3,3',4,4'-tetraimino
      3,3',4,4'-tetrahydrobiphenyl. EPR-supported assignment of NIR absorptions for the
      paramagnetic intermediates.
AB  - A complete EPR and UV-Vis-NIR spectroelectrochemical characterisation has been
      carried out for the series 1(2+/+/0/-/2-) where is the 1 new complex [(mu
      L)[Ru(II)(acac)2]2], L = 3,3',4,4'-tetraimino-3,3',4,4'-tetrahydrobiphenyl. The
      paramagnetic intermediates are identified as the anion radical (L*-) complex 1*-
      with a long-wavelength intra-ligand transition at 2160 nm and as the weakly
      coupled diruthenium(II,III) species 1+ (Kc= 10(3)) with a low-intensity
      intervalence charge transfer (IVCT) band at 1570 nm. DFT calculations using ADF
      and Gaussian 03 programs support these assignments.

PMID- 15252496
TI  - The triruthenium complex [[(acac)2Ru(II)]3(L)] containing a conjugated
      diquinoxaline[2,3-a:2',3'-c]phenazine (L) bridge and acetylacetonate (acac) as
      ancillary ligands. Synthesis, spectroelectrochemical and EPR investigation.
AB  - The compound [[(acac)2Ru]3(L)] (1) undergoes three well-separated one-electron
      oxidation and reduction processes. The EPR results indicate electron removal from
      the ruthenium(II) centres on oxidation and the occupation of a largely L-based
      molecular orbital on reduction. In spite of well-separated (DeltaE > or = 340 mV)
      oxidation no obvious intervalence charge transfer bands were detected in the Vis,
      NIR or IR regions, suggesting very weak electronic coupling between the metal
      centres in the mixed-valent intermediates 1+ and 1(2+). The separated (DeltaE >
      or = 540 mV) stepwise reduction produces weak near-infrared features associated
      with partially occupied pi* orbitals of L, the unusually high g anisotropy in the
      EPR spectrum of 1- is attributed to the occupation of a degenerate MO by the
      unpaired electron.

PMID- 15252497
TI  - Molecular structure of 1,1,2,2-tetra-tert-butyldisilane: unusual structural
      motifs in sterically crowded disilanes.
AB  - The molecular structure of 1,1,2,2-tetra-tert-butyldisilane has been determined
      by gas-phase electron diffraction supported by ab initio calculations, in the
      solution phase by Raman spectroscopy, and in the solid phase by Raman
      spectroscopy and X-ray crystallography. The gas-phase structure (C2 symmetry) was
      found to be almost anticlinal, a most unusual and unexpected result. In the
      favoured conformation, contact between tert-butyl groups at each end of the
      molecule is avoided by a large deviation of the angles around the silicon atoms
      from the parent tetrahedral angle of 109.5 degrees. In fact, the Si-Si-C angles
      returned from the gas electron diffraction refinement are 117.0(5) and 110.7(6)
      degrees, indicating the large degree of flexibility about the silicon centres.
      The ab initio methods and gas electron diffraction results indicate that there is
      only one conformer of But2HSiSiHBut2 in the gaseous mixture. Variable temperature
      Raman studies indicate the possibility of a further higher energy conformer
      existing in the liquid phase. However, this seems quite improbable from other
      observations made for the Raman spectra at all temperatures. The X-ray structure
      is close to that observed in the gas phase, with phiHSiSiH = 94.2(18) degrees.
      There is a large amount of disorder about one of the silicon postions and one of
      the tert-butyl groups within the crystal structure, which makes detailed direct
      comparison with the gaseous structure difficult.

PMID- 15252498
TI  - Embracing ligands. Synthesis, characterisation and the correlation between 59Co
      NMR and ligand field parameters of Co(III) complexes with a new class of nitrogen
      thioether multidentate ligand.
AB  - The syntheses of the hexadentate ligands 2,2,10,10-tetra(methyleneamine)-4,8
      dithiaundecane (PrN4S2amp), 2,2,11,11-tetra(methyleneamine)-4,9-dithiadodecane
      (BuN4S2amp), and 1,2-bis(4,4-methyleneamine)-2-thiapentyl)benzene (XyN4S2amp) are
      reported and the complexes [Co(RN4S2amp)]3+ (R = Pr, Bu, Xy) characterised by
      single crystal X-ray study. The low-temperature (11 K) absorption spectra have
      been measured in Nafion films. From the observed positions of both spin-allowed
      1A1g-->1T1g and 1A1g-->1T2g and spin forbidden 1A1g-->3T1g and 1A1g-->3T2g bands,
      octahedral ligand-field parameters (10Dq, B and C) have been determined. DFT
      calculations suggest that significant interaction between the d-d and CT
      excitations occurs for the complexes. The calculations offer an explanation for
      the observed deviations from linearity of the relationship between 59Co
      magnetogyric ratio and beta(DeltaE)(-1)(beta= the nephelauxetic ratio; DeltaE the
      energy of the 1A1g-->1T1g transition) for a series of amine and mixed
      amine/thioether donor complexes.

PMID- 15252499
TI  - Novel one-dimensional structures and solution behaviour of copper(II) bromide and
      chloride complexes of a new pentapyridyldiamine ligand.
AB  - Copper(II) bromide and chloride complexes of the new heptadentate ligand 2,6
      bis(bis(2-pyridylmethyl)amino)methylpyridine (L) have been prepared. For the
      bromide complexes, chains of novel, approximately C2-symmetric, chiral
      [Cu2(L)Br2]2+ 'wedge-shaped' tectons are found. The links between the dicopper
      tectons and the overall chirality and packing of the chains are dictated by the
      bromide ion content, not the counter anion. In contrast, the chloride complexes
      exhibit linked asymmetric [Cu2(L)Cl3]+ tectons with distinct N3CuCl2 and N4CuCl2
      centres in the solid. The overall structures of the dicopper bromide and chloride
      units persist in solution irrespective of the halide. The redox chemistry of the
      various species is also described.

PMID- 15252500
TI  - CpRu(CO)2(BF4) and [CpFe(CO)2(THF)]+ on mesoporous silica as adsorbents for the
      removal of dibenzothiophenes from hydrocarbon solutions.
AB  - The complexes, CpRu(CO)2(BF4) and [CpFe(CO)2(eta2-2-methylpropene)][BF4], react
      with dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-Me2DBT) to give
      [CpRu(CO)2(DBT)][BF4] and [CpFe(CO)2(4,6-Me2DBT)][BF4], whose structures were
      established by X-ray diffraction studies. The same types of products are obtained
      when dibenzothiophenes react with CpRu(CO)2(BF4) and [CpFe(CO)2(THF)][BF4] that
      are adsorbed on the mesoporous silica SBA-15. DRIFT and XPS studies indicate that
      CpRu(CO)2(BF4) and [CpRu(CO)2(DBT)][BF4] are adsorbed on the SBA-15 by hydrogen
      bonding of the BF4- anions to surface Si-O-H groups. CpRu(CO)2(BF4)/SBA-15
      removes 99% of the DBT in a 45% toluene/55% hexanes simulated petroleum
      feedstock. This solid phase extractant is less successful for sterically-hindered
      4,6-Me2DBT, as only 72% of it is removed. The results show that CpRu(CO)2(BF4)
      can be immobilized by adsorption on mesoporous silica and that it reacts with
      dibenzothiophenes in the adsorbed form, CpRu(CO)2(BF4)/SBA-15, in much the same
      way that it reacts in solution.

PMID- 15252501
TI  - Mixed-metal sandwich complexes [M(II)2(H2O)2Fe(III)2(P2W15O56)2]14- (M(II) = Co,
      Mn): synthesis and stability. The molecular structure of
      [M(II)2(H2O)2Fe(III)2(P2W15O56)2]14-.
AB  - Two new mixed-metal sandwich complexes [M(II)2(H2O)2Fe(III)2(P2W15O56)2]14-
      (abbreviated [M2Fe2P4W30], M(II) = Co(II), Mn(II)) were obtained at pH 3 by
      addition of M2+ to [Na2(H2O)2Fe(III)2(P2W15O56)2]16- (abbreviated [Na2Fe2P4W30])
      without substitution in the alpha-[P2W15O56]12- (abbreviated [P2W15]) units.
      Their X-ray structures are reported. At lower pH, back conversion to
      [Na2Fe2P4W30] was followed by 31P NMR, electrochemistry and UV-visible
      spectroscopy. The preparation and the characterization in solution of the
      lacunary intermediate [NaCo(II)(H2O)2Fe(III)2(P2W15O56)2]15- (abbreviated
      [NaCoFe2P4W30]) is also described.

PMID- 15252502
TI  - A unique coordination environment for an ion: EXAFS studies and bond valence
      model approach of the encapsulated cation in the Preyssler anion.
AB  - X-Ray absorption spectroscopy was used to probe the coordination of different
      encrypted cations in the Preyssler anions [M(n+)P5W(30)O(110)]((15-n)-)(M(n+)=
      Sr2+, Am3+, Eu3+, Sm3+, Y3+, Th4+, U4+ in decreasing order of ionic radius, IR),
      hereafter abbreviated [M(n+)PA](15-n)-. The increase of the M-W distance and the
      decrease of the M-P distance with increasing M ionic radius reveal that the M
      cation is displaced along the C5 axis within the Preyssler cavity. The slight
      change (0.07 A) of the M-O distance that does not correspond to the IR difference
      of 0.27 A confirms that the cavity retains its rigidity upon cation substitution.
      Geometric modeling of the encapsulated cation in the channel was performed for
      comparison to the EXAFS results. The position of the cation in the cavity was
      calculated as well as the M-O10, -W5 and -P5 distances. This modeling confirms
      the cation displacement toward the center of the Preyssler anion as the cation
      size increases, which is understood in terms of the non-homogenous electrostatic
      potential present within the cavity. The bond valence model approach was applied
      to obtain experimental bond valences. Only the bond valence sum (BVS) of Am3+ is
      close to its actual charge. Sums smaller than the actual valences of the +3 and
      +4 ions (2.39-2.63 for +3 cations, Y, Sm, Eu; 3.17 and 3.38 for +4 cations, U and
      Th, respectively) were obtained, and a larger sum (2.89) was obtained for Sr2+.
      The deviations from the formal M sums of the encapsulated ions are attributed to
      the rigidity of the Preyssler framework. The tendency toward coordinative
      unsaturation for electroactive cations, such as Eu3+, is thought to be the
      driving force for facile reduction. Unlike other inorganic chelating ligands, the
      Preyssler anion provides a unique redox system to stabilize an electroactive
      cation in a low oxidation state.

PMID- 15252503
TI  - Steric control in the oligomerisation of phosphazane dimers; towards new
      phosphorus-nitrogen macrocycles.
AB  - The reaction of [ClP(mu-NtBu)]2 (1) with H2O (1 : 2 equivalents) in the presence
      of excess Et3N gives the new chain compound [(mu-O)[P(mu-NtBu)2P(H)=O]2] (3),
      consisting of two P2N2 rings linked by a mu-O atom and terminating in P(V)(H)=O
      groups. A similar chain species is obtained from the reaction of the lithiate of
      [(tBuNH)P(mu-NtBu)2P(H)=O] (5) with [ClP(mu-NtBu)2P(NHtBu)] (2), the product
      being [(mu-O)[P(mu-NtBu)2P(NHtBu)]2] (6). Compounds 3 and 6 are the first
      examples of O-bridged chain phosphazanes and potential precursors to new
      phosphorus-nitrogen macrocycles. The syntheses and X-ray structures of 3, 5 and 6
      are reported.

PMID- 15252504
TI  - Novel Cd(II) coordination polymers with flexible disulfoxide ligands: effects of
      ligand spacers, terminal groups and counter anions on the complex framework
      formations.
AB  - Five novel Cd(II) coordination polymers with three structurally related flexible
      disulfoxide ligands, [[Cd(L1)3](ClO4)2]n (1), [[Cd(L2)3](ClO4)2(CHCl3)]n (2),
      [Cd(L2)(NO3)2(H2O)]n (3), [Cd2(L3)2(NO3)4]n (4) and [[Cd(L3)3](ClO4)2]n (5),
      where L1= 1,3-bis(phenylsulfinyl)propane, L2= 1,4-bis(phenylsulfinyl)butane and
      L3= 1,4-bis(ethylsulfinyl)butane, were synthesized and structurally determined by
      X-ray diffraction. Complex 1 has a 2D layer structure, in which part of the L1
      ligands bridge the Cd(II) ions to form double-bridging chains and the other part
      of ligands link such chains to form a 2D framework. Complexes 2 and 5 are
      isomorphous, showing unusual 2D (3,6) network structures containing triangular
      grids. Complex 3 adopts a 2D (4,4) network formed by L2 linking the NO3- bridged
      (Cd-O-N-O-)n 1D zigzag chains. By contrast, is a 1D chain, in which two Cd(II)
      centers are bridged by mu2-O of sulfoxide groups to form a dinuclear unit, and L3
      ligands link such dinuclear units to form a 1D double-bridging chain. The
      structural differences among such complexes show that the ligand nature and
      counter anions have important influences on the complex structures, which may
      provide a rational method for controlling the framework formation in metal
      organic coordination polymers.

PMID- 15252505
TI  - A severely interrupted germanate zeolite framework synthesised from isolated
      double four-ring units.
AB  - A new germanate zeolite framework has been prepared by first determining the
      reaction conditions required to prepare a molecular analogue of the zeolite
      double four-ring secondary building unit and then altering the conditions so as
      to encourage condensation of these units. The resultant material is a severely
      interrupted solid showing an unusual two dimensional channel system. It is also
      one of the most open frameworks yet discovered. The material was characterised
      using single crystal X-ray diffraction at a synchrotron source and solid state
      magic angle spinning NMR.

PMID- 15252506
TI  - Two complexes of Sm(II) with crown ethers-electrochemical synthesis, structure
      and spectroscopy.
AB  - Two complexes of divalent samarium have been synthesized by electrochemical
      reduction in methanol-tetrahydrofuran solutions: [Sm(18-crown-6)(ClO4)2] and
      [Sm(15-crown-5)2](ClO4)2. In [Sm(18-crown-6)(ClO4)2] the metal cation is ten
      coordinate and its coordination sphere comprises six oxygen atoms of the crown
      ligand and four oxygen atoms from two perchlorate anions. [Sm(15-crown
      5)2](ClO4)2 shows a sandwich structure with decacoordinate samarium located
      between two 15-crown-5 molecules. At 77 K both compounds show f-f luminescence
      originating from the 5D0 level, and also the 15-crown-5 complex shows a weak
      luminescence in the range 20000-25000 cm(-1), which has been tentatively
      interpreted as originating from 3P0 and 5H3 levels. At room temperature the
      emission of [Sm(15-crown-5)2](ClO4)2 is dominated by broad f-d bands. In the
      excitation spectra some Fano resonances have been observed. The 18-crown-6
      compound is unstable, but the 15-crown-5 compound is fairly stable in air.

PMID- 15252507
TI  - QALE analysis of CO dissociative kinetics of Ru(CO)4L (L = P-donor ligands):
      accelerating effects of hydrogen in PHnR(3 - n) ligands (n = 1-2).
AB  - Studies of CO-dissociative substitution reactions of the complexes Ru(CO)4L (L =
      a wide variety of P-donor ligands) have been extended and analysis of the results
      by the QALE methodology has been refined (QALE = quantitative analysis of ligand
      effects). Rates increase substantially with increasing size of L, mainly as a
      consequence of increasingly favourable activation entropies. These can be
      associated with increasing Ru-CO bond breaking that is compensated enthalpically
      by increasing Ru-P bond making allowed by release of steric strain. Explicit
      allowance for pi-acidity shows that these effects are just significant while
      sigma-donor and aryl effects are negligible. However, pendent hydrogen atoms,
      attached directly to the phosphorus atoms, have a pronounced and unique positive
      effect on the rates, with significant kinetic isotope effects (KIE). This is
      associated with the novel occurrence of direct Ru-H or incipient Ru-(eta2-P-H)
      agostic bond making as the CO ligand departs.

PMID- 15252508
TI  - Molecular and supramolecular features of oxo-peroxovanadium complexes containing
      O3N, O2N2 and ON3 donor sets.
AB  - The complexes [VO(O2)Hbpa]+ (1a), [VO(O2)bpa] (1b, Hbpa = bis(picolyl)-beta
      alanine), [VO(O2)heida]- (2, H2heida =N-(2-hydroxyethyl)iminodiacetic acid),
      [VO(O2)(3OH-pic)2]- (3a), [VO(O2)(3OH-pic)2]-/[V(O2)2(3OH-pic)2]- (3b, 3OH-pic =
      3-hydroxypicolinic acid), [VO(O2)(3OH-pa)2] (6, 3OH-pa = 3-hydroxypicolylamide),
      [VO2(3OH-pic)2]- (4), [VO(tBuO2)(3OH-pic)2] (5) and [VO(tBuO2)(3OH-pa)2]2+ (7)
      have been characterised. The structures of 21a[ClO4].1b.2.25H2O, K.2H2O,
      [NH4].H2O and [nBu4]3b are reported. Supramolecular patterns arise from
      intermolecular hydrogen bonds, the relevance of which for the peroxo/hydroperoxo
      intermediates in oxo transfer reactions catalysed by vanadate-dependent
      haloperoxidases is addressed. Specific solution patterns have been analysed by
      51V and 17O NMR.

PMID- 15252509
TI  - Synthesis and P-P cleavage reactions of [P(X)X']2; X-ray structures of
      [Co[P(X)X'](CO)3] and P4[P(X)X']2[X = N(SiMe3)2, X'= NPri2].
AB  - Treatment of P(X)(X')Cl with KC8 gave the crystalline diphosphine [P(X)X']2 (1)
      which dissociated reversibly into the phosphinyl radical *P(X)X' (2), a plausible
      intermediate in the reaction of with [Cr(CO)6], [Co(NO)(CO)3] or P4, yielding
      [Cr[P(X)X']2(CO)3] (3), [Co[P(X)X'](CO)3] (4), or 1,4-P4[P(X)X']2 (5); the P(X)X'
      substituent is pyramidal at P in but planar in [X = N(SiMe3)2, X'= NPri2].

PMID- 15252510
TI  - Self-assembly of molecular squares based on easy-to-prepare multidentate Schiff
      base ligands.
AB  - The choice of ligands with different spacer length and coordination orientation
      leads to size, shape and packing differences between two self-assembled molecular
      squares [Zn4H8L1(4)][PF6]5[NO3]3.S (1) and [Zn4H8L2(4)][PF6]6[NO3]2.S (2) (S =
      solvent), formed from Zn(NO3)2 and two easy-to-prepare bistridentate Schiff-base
      ligands.

PMID- 15252511
TI  - Robust hydrogen-bonded self-assemblies from biimidazole complexes. Synthesis and
      structural characterization of [M(biimidazole)2(OH2)2]2+ (M = Co2+, Ni2+)
      complexes and carboxylate modules.
AB  - A robust heteromeric hydrogen-bonded synthon [R2(2) (9)-Id] is exploited to drive
      the modular self-assembly of four coordination complexes [M(H2biim)2(OH2)2]2+ (M
      = Co2+, Ni2+) and carboxylate counterions. This strategy allowed us to build
      molecular architectures of 0-, 1-, and 2-dimensions. A hydrogen-bonded 2D-network
      with cavities has been designed, which maintains its striking integrity after
      reversible water desorption-resorption processes.

PMID- 15252512
TI  - Synthesis and characterisation of ruthenium complexes containing a pendent
      catechol ring.
AB  - A series of [Ru(bipy)2L]+ and [Ru(phen)2L]+ complexes where L is 2-[5-(3,4
      dimethoxyphenyl)-4H-1,2,4-triazol-3-yl]pyridine (HL1) and 4-(5-pyridin-2-yl-4H
      1,2,4-triazol-3-yl)benzene-1,2-diol (HL2) are reported. The compounds obtained
      have been characterised using X-ray crystallography, NMR, UV/Vis and emission
      spectroscopies. Partial deuteriation is used to determine the nature of the
      emitting state and to simplify the NMR spectra. The acid-base properties of the
      compounds are also investigated. The electronic structures of [Ru(bipy)2L1]+ and
      Ru(bipy)2HL1]2+ are examined using ZINDO. Electro and spectroelectrochemical
      studies on [Ru(bipy)2(L2)]+ suggest that proton transfer between the catechol and
      triazole moieties on L2 takes place upon oxidation of the L2 ligand.

PMID- 15252513
TI  - 9,10-Anthracene dicarboxylate bridged complexes with M2 quadruply bonded dimetal
      units: [[M2(O2CtBu)3]2(mu-9,10-An(CO2)2)], where M = Mo or W.
AB  - From the reactions between [M2(O2CtBu)4] and 9,10-anthracenedicarboxylic acid in
      toluene, the dicarboxylate bridged complexes [[M2(O2CtBu)3]2(mu-9,10An(CO2)2)],
      have been obtained as microcrystalline yellow (M = Mo) and red (M = W) powders.
      The powders are soluble in THF forming intense red (M = Mo) and green (M = W)
      solutions. The electronic absorption spectra in 2-MeTHF have been recorded as a
      function of temperature (2-298 K) and show a small bathochromic shift on cooling.
      The electronic structures have been investigated by molecular orbital
      calculations employing density functional theory on the model compounds
      [(HCO2)3M2]2(mu-9,10-An(CO2)2) where the M4 unit is constrained to lie in a
      plane. These reveal a minimum energy, gas-phase structure wherein the plane of
      the anthracene is twisted by ca. 54 degrees with respect to its 9,10-carboxylate
      units for both Mo and W. The results of these calculations are correlated with
      the electronic absorption spectral data and the electrochemical measurements (CV
      and DPV) of the first and second oxidation waves. The EPR spectra of the radical
      cations formed by single-electron oxidation with [Cp2Fe](+)[PF6]- in a THF-CH2Cl2
      solvent mixture show that the complexes are valence trapped at ambient
      temperature on the EPR timescale. These results are discussed in the light of
      recent studies of dicarboxylate-linked MM quadruple bonds.

PMID- 15252514
TI  - Synthesis and structure of the incomplete cuboidal clusters [W3Se4H3(dmpe)3]+,
      [W3Se4H(3-x)(OH)x(dmpe)3]+ and [W3Se4(OH)3(dmpe)3]+, and the mechanism of the
      acid-assisted substitution of the coordinated hydrides.
AB  - The novel incomplete cuboidal cluster [W3Se4H3(dmpe)3](PF6), [1](PF6), has been
      prepared by reduction of [W3Se4Br3(dmpe)3](PF6) with LiBH4 in THF solution. The
      trihydroxo complex [W3Se4(OH)3(dmpe)3](PF6), [2](PF6), was obtained by reacting
      [W3Se4Br3(dmpe)3](PF6) with NaOH in MeCN-H2O solution. The complexes [1](PF6) and
      [2](PF6) were converted to their BPh4- salts by treatment with NaBPh4.
      Recrystallisation of [1](BPh4) in the presence of traces of water affords the
      mixed dihydride hydroxo complex [W3Se4H2(OH)(dmpe)3](BPh4). The crystal
      structures of [1](BPh4), [2](BPh4) and [W3Se4H2(OH)(dmpe)3](BPh4) have been
      resolved. Although the [1]+ trihydride does not react with an excess of halide
      salts, reaction with HX leads to [W3Se4X3(dmpe)3]+ (X = Cl, Br). The kinetics of
      this reaction has been studied at 25 degrees C in MeCN-H2O solution (1:1, v/v)
      and found to occur with two consecutive kinetic steps. The first step is
      independent of the nature and concentration of the X(-) anion but shows a first
      order dependence on the concentration of acid (k1 = 12.0 mol(-1) dm(3) s(-1)),
      whereas the second one is independent of the nature and concentration of both the
      acid and added salts (k2 = 0.024 s(-1)). In contrast, the reaction of [2]+ with
      acids occurs in a single step with kobs = 0.63 s(-1)(HCl) and 0.17 s(-1)(HBr).
      These kinetic results are discussed on the basis of the mechanism previously
      proposed for the reactions of the analogous [W3S4H3(dmpe)3]+ cluster, with
      special emphasis on the effects caused by the change of S by Se on the rate
      constants for the different processes involved.

PMID- 15252515
TI  - Structural diversity in the coordination of amidines and guanidines to monovalent
      metal halides.
AB  - A series of structurally characterised, monovalent metal-halide complexes
      incorporating neutral amidine and guanidine ligands is reported. N,N'
      diphenylbenzamidine reacted with copper(I) chloride to afford the bis-ligand
      complex [CuCl(PhC[NPh][NHPh])2]2 (1), that exists as a chlorine bridged dimer in
      the solid state, with a non-symmetrical distribution of NH...Cl interactions
      within the 'Cu2Cl2' metallacycle. In contrast, only one equivalent of the
      guanidine, Me2NC[NiPr][NHiPr] (2), is coordinated in the copper(I) iodide complex
      [CuI(Me2NC[NiPr][NHiPr])]2 (3), which was also isolated as the dimer with
      bridging halide atoms. The molecular structure of the bicyclic guanidine,
      1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-alpha]pyrimidine (hppH), is reported,
      revealing a hydrogen bridged dimer with extensive delocalisation throughout the
      ligand framework. Coordination of hppH to lithium chloride afforded the dimeric
      bis-ligand complex [LiCl(hppH)2]2 (4) in which each hppH molecule interacts with
      a different chlorine atom of the central 'Li2Cl2' core of the molecule via
      NH...Cl hydrogen bonding. In contrast the 2:1 ligand to metal complex is formed
      with silver(I) chloride to afford AgCl(hppH)2 (5), a unique example of a
      monomeric, three-coordinate silver chloride supported by nitrogen-based ligands.
      The series of mixed ligand complexes [CuX(hppH)(PPh3)]n (6, X = Cl, n= 1; 7, X =
      Br, n= 2; 8 X = I, n= 2) have also been synthesised and structurally
      characterised, allowing comparisons of the relative coordinating behaviour of
      hppH and PPh3 as neutral donors at copper(I) centres to be made.

PMID- 15252516
TI  - Stereoselective ligand-exchange reaction of planar-chiral cyclopentadienyl
      ruthenium complexes: thermodynamic control of configuration at a stereogenic
      metal center.
AB  - The reaction of planar-chiral cyclopentadienyl-ruthenium complexes with Bu4NI
      resulted in the formation of iodo complexes with high diastereoselectivity (up to
      >99%de). The stereochemistry of the ruthenium center in the starting material did
      not influence the diastereoselectivity of the products. Epimerization of a
      diastereomerically pure sample gave a mixture of two diastereomers in the same
      ratio as with the ligand-exchange reaction, suggesting that the selectivity is
      determined by the difference in thermodynamic stability between the
      diastereomeric pair of iodo complexes. The ratio of the products depends on the
      nature of the substituent on the cyclopentadienyl ring and P ligands on the
      ruthenium atom. A combination of small substituents on the cyclopentadienyl group
      and small P ligands with strong electron-donating ability favored the formation
      of 2-I. The bulkiness of the substituents on the cyclopentadienyl group or of the
      P ligands, and low electron-donating ability of the P ligands increased the ratio
      of 2-II complexes to 2-I isomer.

PMID- 15252517
TI  - Synthesis and characterisation of transition metal halide complexes of the xylyl
      distibine, 1,2-bis(dimethylstibanylmethyl)benzene.
AB  - Complexes of the title ligand with Cu(I), Ag(I), Au(I), Pd(II), Pt(II), Rh(III),
      and rare examples with Ni(II) and Co(III) have been prepared and characterised by
      analysis, IR, UV-vis, 1H, 63Cu and 59Co NMR spectroscopy and ES+ mass
      spectrometry as appropriate. The structures of [Cu[1,2-C6H4(CH2SbMe2)2]2]BF4,
      [PtCl2[1,2-C6H4(CH2SbMe2)2]], [M[1,2-C6H4(CH2SbMe2)2]2][PF6]2 (M = Pd or Pt), and
      [NiI[1,2-C6H4(CH2SbMe2)2]2]ClO4 have been determined, and the varying chelate
      bite and conformations of the xylyl backbone in these structures are discussed.
      Despite the unfavourable seven-membered chelate ring and the large soft antimony
      donors, 1,2-C6H4(CH2SbMe2)2 proves to be a surprisingly good ligand for late
      transition metals in medium oxidation states.

PMID- 15252518
TI  - Polymeric silver(I) complexes with pyridyl dithioether ligands: experimental and
      theoretical investigations on the coordination properties of the ligands.
AB  - The reactions of four flexible tetradentate ligands, 1,3-bis(2
      pyridylthio)propane (L1), 1,4-bis(2-pyridylthio)butane (L2), 1,5-bis(2
      pyridylthio)pentane (L3) and 1,6-bis(2-pyridylthio)hexane (L4) with AgX (X = BF4
      , ClO4-, PF6-, or CF3SO3-) lead to the formation of seven new complexes:
      [AgL1(BF4)]2 (1), [[AgL2](ClO4)]infinity (2), [[AgL2(CH3CN)](PF6)]infinity (3),
      [[AgL3](BF4)(CHCl3)]2 (4), [[AgL3(CF3SO3)](CH3OH)(0.5)]infinity (5),
      [[Ag2L4(2)](BF4)2]infinity (6), and [[AgL4](PF6)]infinity (7), which have been
      characterized by elemental analyses, IR spectroscopy, and X-ray crystallography.
      Single-crystal X-ray analyses show that complexes 1 and 4 possess dinuclear
      macrometallacyclic structures, and complexes 2, 3 and 5-7 take chain structures.
      In all the complexes, the nitrogen atoms of ligands preferentially coordinate to
      silver atoms to form normal coordination bonds, while the sulfur atoms only show
      weak interactions with silver atoms and the intermolecular AgS weak contacts
      connect the low-dimensional complexes into high-dimensional supramolecular
      networks. Additional weak interactions, such as pi-pi stacking, F...F weak
      interactions, Ag...O contacts or C-H...O hydrogen bonds, also help to stabilize
      the crystal structures. It was found that the parity of the -(CH2)n- spacers (n =
      3-6) affect the orientation of the two terminal pyridyl rings, thereby
      significantly influence the framework formations of these complexes. The
      coordination features of ligands and their conformation changes between free and
      coordination states have been investigated by DFT calculations.

PMID- 15252519
TI  - Magnesium and zinc complexes of a potentially tridentate beta-diketiminate
      ligand.
AB  - The synthesis of the unsymmetrically substituted beta-diketimine, 2-(2
      methoxyphenylimino)-4-(2,6-diisopropylphenylamido)pent-2-ene, (BDI-2)H, is
      described and its complexation chemistry with magnesium and zinc is explored.
      Emphasis is placed on the preparation of alkoxide and amide derivatives for the
      ring-opening polymerisation of lactide; their behaviour as polymerisation
      initiators is compared to analogous compounds supported by the N,N'-bis(2,6
      diisopropylphenyl) beta-diketiminate ligand, BDI-1. (BDI-2)H reacts with Me2Mg to
      give the bis(chelate) complex, (BDI-2)2Mg, 3. Magnesium alkyls supported by BDI-2
      may be prepared by increasing the size of the alkyl group. Hence, lithiation of
      (BDI-2)H affords [(BDI-2)Li]2, 4; its subsequent treatment with iPrMgCl produces
      (BDI-2)MgiPr, 5. Aminolysis of complex using iPr2NH yields the amide complex,
      (BDI-2)MgNiPr2, 6. Zn(NTMS2)2 and ZnEt2 react with (BDI-2)H to give (BDI
      2)Zn(NTMS2), 7, and (BDI-2)ZnEt, 8, respectively. The former is converted into
      the siloxide complex, (BDI-2)Zn(OSiPh3), 9, upon reaction with Ph3SiOH. The
      chloride derivative, (BDI-2)ZnCl, 10, has also been prepared via the reaction of
      ZnCl2 with 4. Crystallographic analysis of compounds, and reveals that the
      potential for (BDI-2) to bind in a tridentate manner is only realised with the
      more electrophilic metals Li and Mg. Compared to their (BDI-1) counterparts,
      complexes 6, 7 and 9 are more active, but less well-controlled, initiators for
      the ring-opening polymerisation of rac-lactide, a consequence of the diminished
      steric protection afforded by (BDI-2) relative to (BDI-1).

PMID- 15252520
TI  - Lanthanide(III)/actinide(III) differentiation in coordination of azine molecules
      to tris(cyclopentadienyl) complexes of cerium and uranium.
AB  - Reaction of azine molecules L with the trivalent metallocenes [M(C5H4R)3](M = Ce,
      U; R = But, SiMe3) in toluene gave the Lewis base adducts [M(C5H4R)3(L)](L =
      pyridine, 3-picoline, 3,5-lutidine, 3-chloropyridine, pyridazine, pyrimidine,
      pyrazine, 3,5-dimethylpyrazine and s-triazine), except in the cases of M = U and
      L = 3-chloropyridine, pyridazine, pyrazine and s-triazine where oxidation of
      U(III) was found to occur. In the pairs of analogous compounds of Ce(III) and
      U(III), i.e.[M(C5H4But)3(L)](L = pyridine, picoline) and [M(C5H4SiMe3)3(L)](L =
      pyridine, lutidine, pyrimidine and dimethylpyrazine), the M-N and average M-C
      distances are longer for M = Ce than for M = U; however, within a series of azine
      adducts of the same metallocene, no significant variation is noted in the M-N and
      average M-C distances. The equilibria between [M(C5H4R)3], L and [M(C5H4R)3(L)]
      were studied by 1H NMR spectroscopy. The stability constants of the uranium
      complexes, KUL, are greater than those of the cerium counterparts, KCeL. The
      values of KML are much greater for R = SiMe3 than for R = But and a linear
      correlation is found between the logarithms of KML and the hydrogen-bond basicity
      pKHB scale of the azines. Thermodynamic parameters indicate that the enthalpy
      entropy compensation effect holds for these complexation reactions. Competition
      reactions of [Ce(C5H4R)3] and [U(C5H4R)3] with L show that the selectivity of L
      in favour of U(III) increases with the [small pi] donor character of the
      metallocene and is proportional to the pi accepting ability of the azine
      molecule, measured by its reduction potential.

PMID- 15252521
TI  - Protonation and coordination properties towards Zn(II), Cd(II) and Hg(II) of a
      phenanthroline-containing macrocycle with an ethylamino pendant arm.
AB  - Protonation and Zn(II), Cd(II) and Hg(II) coordination with the ligand 5
      aminoethyl-2,5,8-triaza-[9]-10,23-phenanthrolinophane (L2), which contains an
      aminoethyl pendant attached to a phenanthroline-containing macrocycle, have been
      investigated by means of potentiometric, 1H NMR and spectrofluorimetric
      titrations in aqueous solutions. The coordination properties of L2 are compared
      with those of the ligand 2,5,8-triaza-[9]-10,23-phenanthrolinophane (L1). Ligand
      protonation occurs on the aliphatic amine groups and does not involve directly
      the heteroaromatic nitrogens. The fluorescence emission properties of L2 are
      controlled by the protonation state of the benzylic nitrogens: when not
      protonated, their lone pairs are available for an electron transfer process to
      the excited phenanthroline, quenching the emission. As a consequence, the ligand
      is emissive only in the highly charged [H3L2]3+ and [H4L2]4+ species, where the
      benzylic nitrogens are protonated. Considering metal complexation, both [ML1]2+
      and [ML2]2+ complexes (M = Zn(II) and Cd(II)) are not emissive, since the
      benzylic nitrogens are weakly involved in metal coordination, and, once again,
      they are available for quenching the fluorescence emission. Protonation of the L2
      complexes to give [MHL2]3+ species, instead, leads to a recovery of the
      fluorescence emission. Complex protonation, in fact, occurs on the ethylamino
      group and gives a marked change of the coordination sphere of the metals, with a
      stronger involvement in metal coordination of the benzylic nitrogens;
      consequently, their lone pairs are not available for the process of emission
      quenching.

PMID- 15252522
TI  - The coordination chemistry of the hydrotris(3-diphenylmethylpyrazol-1-yl)borate
      (Tp(CHPh2)) ligand.
AB  - The new ligand, hydrotris[3-(diphenylmethyl)pyrazol-1-yl]borate, Tp(CHPh2), has
      been synthesized and its coordination chemistry was compared with that of the
      analogous Tp(iPr). The new ligand was converted to a variety of complexes, such
      as M[Tp(CHPh2)]X (M = Co, Ni, Zn; X = Cl, NCO, NCS), Pd[Tp(CHPh2)][eta3
      methallyl], Co[Tp(CHPh2)](acac), and Co[Tp(CHPh2)](scorpionate ligand). Compounds
      Tl[Tp(CHPh2)], 1, Co[Tp(CHPh2)]Cl, 2, Co[Tp(CHPh2)](NCS)(DMF), 3,
      Ni[Tp(CHPh2)](NCS)(DMF)2, 4, Co[Tp(CHPh2)](acac), 5, Co[Tp(CHPh2)][Ph2Bp], 6,
      Co[Tp(CHPh2)][Bp(Ph)], 7, Co[Tp(CHPh2)][Tp], 8, and (Ni[Tp(CHPh2)])2[C2O4](H2O)2,
      9, were structurally characterized.

PMID- 15252523
TI  - Dinuclear Zn2+ complexes in the hydrolysis of the phosphodiester linkage in a
      diribonucleoside monophosphate diester.
AB  - Dizinc complexes that were formed from 2:1 mixtures of Zn(NO3)2 and dinucleating
      ligands TPHP (1), TPmX (2) or TPpX (3) in aqueous solutions efficiently
      hydrolyzed diribonucleoside monophosphate diesters (NpN) under mild conditions.
      The dinucleating ligand affected the structure of the aquo-hydroxo-dizinc core,
      resulting in different characteristics in the catalytic activities towards NpN
      cleavage. The pH-rate profile of ApA cleavage in the presence of (Zn2+)(2)-1 was
      sigmoidal, whereas those of (Zn2+)(2)-2 and (Zn2+)(2)-3 were bell-shaped. The pH
      titration study indicated that (Zn2+)(2)-1 dissociates only one aquo proton (up
      to pH 12), whereas (Zn2+)(2)-2 dissociates three aquo protons (up to pH 10.7).
      The observed differences in the pH-rate profile are attributable to the various
      distributions of the monohydroxo-dizinc species, which are responsible for NpN
      cleavage. As compared to that using (Zn2+)(2)-1, the NpN cleavage using (Zn2+)(2)
      2 showed a greater rate constant, with a higher product ratio of 3'-NMP/2'-NMP.
      The saturation behaviors of the rate, with regard to the concentration of NpN,
      were analyzed by Michaelis-Menten type kinetics. Although the binding of
      (Zn2+)(2)-2 to ApA was weaker than that of (Zn2+)(2)-1, (Zn2+)(2)-2 showed a
      greater kcat value than (Zn2+)(2)-1, resulting in higher ApA cleavage activity of
      the former.

PMID- 15252524
TI  - Anionic carbonato and oxalato cobalt(III) nitrogen mustard complexes.
AB  - Synthetic approaches to cobalt(III) complexes [Co(L)(L')2] containing the
      bidentate dialkylating nitrogen mustard N,N-bis(2-chloroethyl)-1,2-ethanediamine
      (L = dce) together with anionic ancilliary ligands (L') which are either
      carbonato (CO3(2-)), oxalato (ox2-), bis(2-hydroxyethyl)dithiocarbamato (bhedtc
      ), 2-pyridine carboxylato (pico-) or 2-pyrazine carboxylato (pyzc-) were
      investigated. Synthetic routes were developed using the related amines N,N
      diethyl-1,2-ethanediamine (dee) and 1,2-ethanediamine (en). The complexes
      [Co(CO3)2(L)]- (L = dee 1, dce 2), [Co(ox)2(L)]- (L = dee 3, dce 4),
      [Co(bhedtc)2(dee)]+ 5, [Co(bhedtc)2(en)]+ 6, mer-[Co(pico)3], mer-[Co(pyzc)]3 7
      and [Co(pico)2(dee)]+ 8 were prepared and were characterised by IR, UV-Vis, 1H
      and 13C[1H] NMR spectroscopy, mass spectrometry and cyclic voltammetry.
      [Co(bhedtc)2(en)]BPh4 6b and trans(O)-[Co(pico)2(dee)]ClO4 8 were characterised
      by X-ray crystallography. In vitro biological tests were carried out on complexes
      1-4 in order to assess the degree to which coordination of the mustard to cobalt
      attenuated its cytotoxicity, and the differential toxicity in air vs. nitrogen.

PMID- 15252525
TI  - Organoplatinum(IV) tris-chelate complexes, each having a cyclic metallacarbonate
      ring: synthesis, characterization and kinetic studies of the formation.
AB  - The complexes [Pt[(CH2)4](NN)], 1a (NN = 2,2'-bipyridine) and 1b (NN = 1,10
      phenanthroline) react with 2,3-epoxypropylphenyl ether in the presence of CO2 to
      give tris-chelate platina(IV)cyclopentane complexes characterized by 1H and 13C
      NMR spectroscopy as [Pt[(CH2)4](CH2CHCH2OPhOCO2)(NN)], 2. The reactions proceed
      by the SN2 mechanism and the rates were independent of concentration of CO2. It
      is demonstrated that for 1a, the reaction proceeds 2.32 times faster than the
      similar reaction in which the dimethyl analog, [PtMe2(2,2'-bipyridine)], is used.
      The analog tris-chelate complex [Pt[(CH2)4](CH2CHPhOCO2)(phen)], 3a, was
      similarly synthesized.

PMID- 15252526
TI  - Cross-couplings in the elaboration of luminescent bis-terpyridyl iridium
      complexes: the effect of extended or inhibited conjugation on emission.
AB  - The utility of Suzuki cross-coupling methodology for the in situ elaboration of
      bromo-functionalised bis-terpyridyl iridium(III) complexes has been explored. The
      complex [Ir(tpy)(tpy-phi-Br)]3+ [tpy-phi-Br = 4'-(4-bromophenyl)-2,2':6',2''
      terpyridine] undergoes palladium-catalysed cross-coupling with aryl boronic acids
      to yield biaryl-substituted complexes directly. The biphenyl and 4-cyanobiphenyl
      substituted products display relatively intense, long-lived (tau > 100 mus)
      yellow emission in degassed aqueous solution at room temperature, assigned to a
      3pi-pi* state. A 4-aminobiphenyl-substituted analogue displays an additional low
      energy absorbance band, attributed to an intraligand charge-transfer (ILCT)
      excited state, and is scarcely emissive under the same conditions. The
      iridium(III) complex of 4'-mesityl-terpyridine is also reported. Its emission is
      much shorter-lived, with a spectral profile resembling that of unsubstituted
      [Ir(tpy)2]3+, confirming the need for the attainment of a roughly coplanar
      geometry for stabilisation of the 3pi-pi* excited state.

PMID- 15252527
TI  - Rationalisation of weak ferromagnetism in manganese(III) chains: the relation
      between structure and ordering phenomena.
AB  - The synthesis, structure and magnetic properties of the one-dimensional chain
      compounds [Mn(cyclam)(SO4)]ClO4.H2O (1) and [Mn(cyclam)(HCOO)](CF3SO3)(ClO4) (2)
      are reported. Cyclam is the cyclic tetradentate ligand 1,4,7,11
      tetraazacyclotetradecane. Both chain compounds exhibit antiferromagnetic
      interactions within the chains. A magnetic ordering phase transition at 5.5 K in
      (1) is investigated by magnetisation measurements along the three principal
      crystallographic axes of a single crystal and the results show unambiguously that
      the ferromagnetic ordering is only taking place along one crystallographic axis.
      The spin structure of the magnetic ordered phase and the magnitude of the
      ferromagnetic moment are correlated with the crystal structure and symmetry of
      the compound.

PMID- 15252528
TI  - Design and coordination behavior of the first selective recognition ligand of
      147Pm(III).
AB  - A new amide tripodal ligand, 6-[2-(2-diethylamino-2-oxoethoxy)ethyl]-N,N,12
      triethyl-11-oxo-3,9-dioxa-6,12-diazatetradecanamide (4) has been designed and
      synthesized for the recognition of rare earth ions. Three representative
      complexes of trivalent lighter (La), middle (Gd), and heavier (Er) rare earth
      ions with 4 were synthesized and characterized by X-ray crystallography. In the
      complex, the heptadentate forms a cup-like coordination cavity encapsulating the
      central ion. Different supramolecular complex dimers are constructed by pi-pi
      interaction and van der Waals forces in accordance with the lanthanide
      contraction. The differences of the cavity and dimer structures were investigated
      further by assessing the separation efficiency of in multitrace solvent
      extraction of rare earth ions from picrate acid solution and the ligand has the
      best separation factor for 147Pm(III).

PMID- 15252529
TI  - Acid-base equilibria of various oxidation states of aqua-ruthenium complexes with
      1,10-phenanthroline-5,6-dione in aqueous media.
AB  - Syntheses and pH dependent electrochemical properties of aqua-ruthenium(II)
      complexes, [Ru(trpy)(PDA-N,N')(OH2)](ClO4)2 ([1](ClO4)2) and [Ru(trpy)(PD
      N,N')(OH2)](ClO4)2 ([2](ClO4)2) (trpy = 2,2':6',2''-terpyridine, PDA = 6-acetonyl
      6-hydroxy-1,10-phenanthroline-5-one, PD = 1,10-phenanthroline-5,6-dione) are
      presented. Treatment of [Ru(trpy)(PD-N,N')Cl](PF6) with AgClO4 in a mixed solvent
      of acetone and H2O selectively produced the acetonyl-PD complex [1](ClO4)2, and
      the similar treatment in a mixed solvent of 2-methoxyethanol and H2O gave the PD
      complex [2](ClO4)2. The molecular structures of both complexes were determined by
      X-ray structural analysis. The proton dissociation constants of various
      oxidations state of [1]2+ and [2]2+ were evaluated by simulation of E(1/2) values
      of those redox potentials depending on pH. The simulation revealed that the
      acetonyl-PD complex [1]2+ underwent successive Ru(II)/Ru(III) and Ru(III)/Ru(IV)
      redox couples though the two redox reactions were not separated in the cyclic
      voltammograms. The redox behavior of [2]2+ in H2O is reasonably explained by not
      only the similar successive metal-centered redox reactions but also simultaneous
      two-electron quinone/catechol redox couple of the PD ligand including the
      contribution of hydration on a carbonyl carbon.

PMID- 15252530
TI  - The influence of the boat-to-chair conversion on the demetallation of the
      nickel(II) complex of an open-chain tetramine containing a piperazine fragment.
AB  - The nickel(II) complex with an open chain tetramine containing a piperazine
      fragment (1) displays an unusual resistance to demetallation in acidic solution
      and exhibits a lifetime of about five minutes in a solution 0.1 M in HClO4 and
      7.0 M in NaClO4. Sluggishness with respect to the demetallation is ascribed to
      the occurrence of the boat-to-chair conformational conversion of the piperazine
      fragment, which implies the passage through the highly energetic half-boat
      transition state. The use of a high concentration of the inert electrolyte
      induces a 'salting out' effect on both thermodynamics (stability of metal
      complexes is enhanced) and kinetics (resistance to demetallation is increased).

PMID- 15252531
TI  - Synthesis, structure and reactivity of ferrio-chloro-phosphanes, -arsanes and 
      stibanes [(CO)2(eta5-C5Me5)FePn(Cl)R] (Pn = P, As, Sb); R =
      tetramethylcyclopentadienyl, 2,7-di-tert-butylfluorenyl, 2,7-di-tert-butyl-9
      trimethylsilylfluorenyl) as precursor to novel metallo-phosphaalkenes, 
      arsaalkenes, and -stibaalkenes.
AB  - Reaction of one equivalent of the complexes [FeCp*(CO)2PnCl2] (Pn = P, As, Sb)
      with tetramethylcyclopentadienyllithium afforded compounds
      [FeCp*(CO)2[Pn(Cl)(C5Me4H)]]. Dehydrochlorination by means of tert-butyllithium
      led to decomposition. Only in the case of the phosphorus compound was evidence
      for the initial formation of a phosphaalkene given by 31P NMR spectroscopy.
      Similarly treatment of equimolar amounts of [FeCp*(CO)2PnCl2] with 2,7-di-tert
      butyl-9-H-fluorenyllithium or 2,7-di-tert-butyl-9-trimethylsilylfluorenyllithium
      yielded the asymmetrically substituted ferriopnicogenanes [FeCp*(CO)2[Pn(Cl)-9-R
      Fl*]] (Pn = P, As, Sb; R = H, Me3Si; Fl* = 2,7-di-tert-butylfluorenylidene).
      Dehydrohalogenation of [FeCp*(CO)2[Pn(Cl)-9-H-Fl*]] with lithium diisopropylamide
      resulted in the formation of the anticipated phosphaalkene [FeCp*(CO)2[P = Fl*]],
      whereas in the case of the arsenic and antimony derivatives the novel
      ferriopnicogenanes [FeCp*(CO)2[Pn(9-H-Fl*)2]] (Pn = As, Sb) were obtained as
      products. The new compounds were characterized by elemental analyses and spectra
      (IR, 1H, 13C, 29Si, 31P NMR). The molecular structures of
      [FeCp*(CO)2[Pn(Cl)(C5Me4H]]] (Pn = As, Sb), [FeCp*(CO)2[As(Cl)(9-Me3Si-Fl*)]] and
      [FeCp*(CO)2[Sb(9-H-Fl*]2] were elucidated by single X-ray diffraction analyses.

PMID- 15252532
TI  - [Ru(TAP)2(dppz)]2+: a DNA intercalating complex, which luminesces strongly in
      water and undergoes photo-induced proton-coupled electron transfer with guanosine
      5'-monophosphate.
AB  - The lowest excited state of [Ru(TAP)2(dppz)]2+ (TAP = 1,4,5,8
      tetraazaphenanthrene, dppz = dipyrido[3,2-a:2',3'-c]phenazine) 1 is strongly
      luminescent, even in water, and very oxidizing. Therefore it is able to oxidise
      not only guanosine-5'-monophosphate (GMP), as demonstrated by laser flash
      photolysis, but also guanine-containing polynucleotides such as calf thymus DNA
      and [poly(dG-dC)]2. The luminescence quenching was found to be faster in H2O than
      in D2O, as is the back reaction, indicating that both processes probably proceed
      by proton-coupled electron transfer. These properties, that are controlled by the
      triplet MLCT state in which the charge has been transferred from the Ru to a TAP
      ligand, contrast with those of the well known [Ru(phen)2(dppz)]2+ 2.

PMID- 15252533
TI  - Stable gold(III) complexes with thiosemicarbazone derivatives.
AB  - Novel thiosemicarbazonato complexes of gold(III) have been prepared from
      reactions of [Au(damp-C1,N)Cl2(damp- = 2-(N,N-dimethylaminomethyl)phenyl) or
      [NBu4][AuCl4] with 2-pyridineformamide thiosemicarbazones (HL). The
      thiosemicarbazones deprotonate and coordinate as mononegative, tridentate NNS
      ligands to gold to give [Au(Hdamp-C1)(L)]Cl2 or [AuCl(L)]Cl complexes. The
      organometallic damp- ligand is protonated during the reactions and the Au-N bond
      is cleaved. The [AuCl(L)]+ cations represent the first gold(III) complexes with
      thiourea derivatives which are not stabilised by an additional organometallic
      ligand. Reactions of [NBu4][AuX4](X = Cl, Br) with diphenylthiocarbazone
      (dithizone) result in reduction of the metal and the formation of gold(I)
      complexes of the composition [AuX(SCN4-3,4-Ph2)] where SCN4-3,4-Ph2 is 3,4
      diphenyltetrazole thione which is formed from cyclisation of dithizone.

PMID- 15252534
TI  - Bi- and poly-metallic cyanide-bridged complexes of the redox-active
      cyanomanganese nitrosyl unit [Mn(CN)(PR3)(NO)(eta-C5H4Me)].
AB  - Cationic nitrile complexes and neutral halide and cyanide complexes, with the
      general formula [MnL1L2(NO)(eta-C5H4Me)]z, undergo one-electron oxidation at a Pt
      electrode in CH2Cl2. Linear plots of oxidation potential, Eo', vs. nu(NO) or the
      Lever parameters, EL, for L1 and L2, allow Eo' to be estimated for unknown
      analogues. In the presence of TlPF6, [MnIL'(NO)(eta-C5H4Me)] reacts with
      [Mn(CN)L(NO)(eta-C5H4Me)] to give [(eta5-C5H4Me)(ON)LMn(mu-CN)MnL'(NO)(eta5
      C5H4Me)][PF6] which undergoes two reversible one-electron oxidations; DeltaE, the
      difference between the potentials for the two processes, differs significantly
      for stable cyanide-bridged linkage isomers. Novel pentametallic complexes such as
      [Mn[(mu-NC)Mn(CNBut)(NO)(eta5-C5H4Me)]4(OEt2)][PF6]2 and [Mn[(mu
      NC)Mn(CNXyl)(NO)(eta5-C5H4Me)]4(NO3-O,O')][PF6], containing a trigonal
      bipyramidal and a distorted octahedral Mn(II) centre, respectively, result either
      from slow decomposition of the binuclear cyanide-bridged species or from the
      reaction of anhydrous MnI2 with four equivalents of [Mn(CN)L(NO)(eta5-C5H4Me)] in
      the presence of TlPF6.

PMID- 15252535
TI  - What kinds of three-dimensional nets are possible with tris-chelated metal
      complexes as building blocks?
AB  - Tris-chelated metal complexes with octahedral geometry are sometimes used as
      building blocks for "self assembly" and "crystal engineering". These versatile
      building blocks easily form honey-comb type 2D nets. However, in this Perspective
      we discuss the different types of 3D nets that can be formed with these starting
      materials using Wells classification, and concentrate on the (10,3) nets. We show
      that several of these, and not only the (10,3)-a net, are possible by analysing
      the geometrical requirements of each net. We note that each possible net implies
      a specific assembly order of Delta or Lambda chirality of the building blocks.

PMID- 15252536
TI  - Hydrolysis of CpTiCl2(TEMPO) and its application on one-pot syntheses of
      CpTiCl(OR)2 complexes.
AB  - The eta1-hydroxylamido half-titanocene complex, CpTiCl2(TEMPO) 1, hydrolyzes
      extremely efficiently to generate (CpTiClO)4 and the protonated hydroxylamine.
      The efficient hydrolysis chemistry provides selective syntheses of CpTi
      dialkoxide and diaryloxide complexes.

PMID- 15252537
TI  - Unexpected formation of a novel macrocyclic tetraphosphine: (RSSR)-1,9-dibenzyl
      3,7,11,15-tetramesityl-1,9-diaza-3,7,11,15-tetraphosphacyclohexadecane.
AB  - The title compound was synthesised in moderate yield via stereoselective self
      assembly of two bisphosphine, four formaldehyde and two primary amine molecules.

PMID- 15252538
TI  - Synthesis and catalytic activity of binuclear titanium imido complexes.
AB  - Treatment of the N-P ligand ArPN(SiMe3)2 with TiCl4 affords the imido-bridged
      binuclear titanium complex [TiCl2(THF)(micro-NArP)]2 (ArP = m-C6H4PR2) which
      reacts with Ni(0) or Pd(ii) to give heterotrinuclear compounds, while activation
      with methylaluminoxane generates a new type of imido-based ethene polymerisation
      catalyst that is tolerant of -PR2 functional groups.

PMID- 15252539
TI  - The first example of a Si-bridged tris(pyridyl) ligand; synthesis and structure
      of [MeSi(2-C5H4N)3LiX](X = 0.2Br, 0.8Cl).
AB  - The low-temperature reaction of MeSiCl3 with 2-Li-C5H4N (1:3 equivalents) in thf
      gives [MeSi(2-C5H4N)3LiX](X = 0.2Br, 0.8Cl), containing the first example of a Si
      bridged tris(pyridyl) ligand.

PMID- 15252540
TI  - NMR and EPR structural delineation of copper(II) complexes formed by kanamycin A
      in water.
AB  - The complexes formed by kanamycin A at three different pH values (5.5, 7.4 and
      12.0) were investigated by NMR and EPR spectroscopy. Paramagnetic relaxation
      contributions to proton relaxation rates were measured using a combination of the
      TOCSY sequence with the inversion recovery experiment in order to gain signal
      resolution in the bulk region. Measured contributions were converted into
      distances and used for structural determination by restrained simulated annealing
      where all possible chair and boat conformations of the rings were taken into
      account. The interaction of the Cu(II) ion with the nitrogen of the C ring is
      apparent at all pH values. At higher pH also the amino group of ring A starts to
      be involved in the metal coordination sphere. This is accompanied by a switch in
      conformation of ring C. Structures are consistent with the involvement in the
      coordination sphere either of the 2' or 4' hydroxyl oxygens at pH 5.5 and the 5
      and the 6' hydroxyl oxygens (or the ring oxygen) at pH 12.0.

PMID- 15252541
TI  - Synthesis and characterisation of cyanodithioimidocarbonate [C2N2S2]2- complexes.
AB  - [PPh4]2[M(C2N2S2)2](M = Pt, Pd) and [Pt(C2N2S2)(PR3)2](PR3= PMe2Ph, PPh3) and
      [Pt(C2N2S2)(PP)](PP = dppe, dppm, dppf) were all obtained by the reaction of the
      appropriate metal halide containing complex with potassium
      cyanodithioimidocarbonate. The dimeric cyanodithioimidocarbonate complexes
      [[Pt(C2N2S2)(PR3)]2](PR3 = PMe2Ph), [M[(C2N2S2)(eta5-C5Me5)]2](M = Rh, Ir)and
      [[Ru(C2N2S2)(eta6-p-MeC6H4iPr)]2] have been synthesised from the appropriate
      transition metal dimer starting material. The cyanodithioimidocarbonate ligand is
      S,S and bidentate in the monomeric complexes with the terminal CN group being
      approximately coplanar with the CS2 group and trigonal at nitrogen thus reducing
      the planar symmetry of the ligand. In the dimeric compound one of the sulfur
      atoms bridges two metal atoms with the core exhibiting a cubane-like geometry.

PMID- 15252542
TI  - Vinyl and carbene ruthenium(II) complexes from hydridoruthenium(II) precursors.
AB  - The reactions of the hydrido compounds [RuHCl(CO)(L)2][L = PiPr3 (1), PCy3 (2)]
      with HC(triple bond)CR (R = H, Ph, tBu) afforded by insertion of the alkyne into
      the Ru-H bond the corresponding vinyl complexes [RuCl(CHCHR)(CO)(L)2], 3-8, which
      upon protonation with HBF4 gave the cationic five-coordinated ruthenium carbenes
      [RuCl(CHCH2R)(CO)(L)2]BF4, 9-14. Subsequent reactions of the carbene complexes
      with PR3(R = Me, iPr) and CH3CN led either to deprotonation and re-generation of
      the vinyl compounds or to cleavage of the ruthenium-carbene bond and the
      formation of the six-coordinated complexes [RuCl(CO)(CH3CN)2(PiPr3)2]BF4, 17, and
      [RuH(CO)(CH3CN)2(PiPr3)2]X, 18a,b. The acetato derivative [RuH(2
      O2CCH3)(CO)(PCy3)2], 19, also reacted with acetylene and phenylacetylene by
      insertion to yield the related vinyl complexes [Ru(CHCHR)(kappa2
      O2CCH3)(CO)(PCy3)2], 20, 21, of which that with R = H was protonated with HBF4 to
      yield the corresponding cationic ruthenium carbene 22. With [RuHCl(H2)(PCy3)2],
      25, as the starting material, the five-coordinated chloro(hydrido)ruthenium(II)
      compounds [RuHCl(PCy3)(dppf)], 26(dppf = [Fe(eta5-C5H4PPh2)2]),
      [RuHCl[Sb(CH2Ph)3](PCy3)2], 27, and [RuHCl(CH3CN)(PCy3)2], 30, were prepared. The
      reactions of 27 with HCCR (R = H, Ph) gave the hydrido(vinylidene) complexes
      [RuHCl(CCHR)(PCy3)2], 28 and 29, whereas treatment of 30 with HC(triple bond)CPh
      afforded the vinyl compound [RuCl(CHCHPh)(CH3CN)(PCy3)2], 31. The molecular
      structures of 11(R = tBu, L = PiPr3) and 26 were determined crystallographically.

PMID- 15252543
TI  - Dynamic interaction of theory and experiment: total determination of the gas
      phase molecular structure of tri-tert-butylphosphine oxide (OPBut3).
AB  - A new method to aid the determination of structures of sterically crowded
      molecules in the gas phase by dynamically linking the gas-phase electron
      diffraction (GED) refinement process with computational methods has been
      developed. The procedure involves refining the heavy-atom skeleton of the
      molecule using the GED data while continually updating the light-atom positions
      during the refinement using computational methods, in this case molecular
      mechanics. This removes errors associated with the assumption of local symmetry
      for the light-atom groups, which can affect the final values of the heavy-atom
      parameters. The refinement of the molecular structure of tri-tert-butyl phosphine
      oxide has been used to illustrate this new technique, which we call the DYNAMITE
      (DYNAMic Interaction of Theory and Experiment) method. Re-examination of the
      structure using this method has resulted in a shorter P-O distance than was found
      in a less sophisticated anaylsis, and is consistent with the molecule being
      regarded as O=PBut3, rather than O(-)-P+But3.

PMID- 15252544
TI  - Synthesis and characterization of two novel mixed metal tellurates: KGaTeO5 x H2O
      and K3GaTe2O8(OH)2 x H2O.
AB  - Single crystals of KGaTeO5 x H2O and K3GaTe2O8(OH)2 x H2O have been synthesized
      by supercritical hydrothermal techniques using Te(OH)6, Ga2O3 and KOH as
      reagents, and characterized by single crystal X-ray diffraction, thermal
      analysis, IR and Raman spectroscopy. Ion-exchange studies revealed KGaTeO5 x H2O,
      with its open-framework structure, is capable of exchanging both smaller (Na+)
      and larger (Rb+) ions. In addition, higher thermal stability and reversible
      hydration properties were observed for KGaTeO5 x H2O.

PMID- 15252545
TI  - Different modes of aggregation in organoaluminium and -gallium hydroxylamides.
AB  - The organoaluminium and -gallium hydroxylamides (Me2GaONMe2)2, (tBu2AlONMe2)2,
      (tBu2GaONMe2)2 and (Me2AlONiPr2)2 have been prepared by the reaction of the
      hydroxylamines Me2NOH and iPr2NOH with the trialkylmetal compounds
      trimethylgallium, tri-tbutylaluminium and tri-tbutylgallium, respectively. All
      compounds have been characterised by NMR spectroscopy (1H, 13C, 15N, 17O and
      27Al), by mass spectrometry and elemental analyses. The crystal structures of the
      four compounds have been determined, showing that they all form dimers but with
      different modes of aggregation: (Me2GaONMe2)2 has a Ga2O2N2 six-membered ring,
      (tBu2AlONMe2)2 and (Me2AlONiPr2)2 have Al2O2 four-membered rings, (tBu2GaONMe2)2
      forms a Ga2O2N five-membered ring.

PMID- 15252546
TI  - Diastereoselective synthesis of coordination compounds: a chiral tripodal ligand
      based on bipyridine units and its ruthenium(II) and iron(II) complexes.
AB  - The enantiomerically pure chiral tris-chelating ligand (+)-(7S,10R)-L(L)
      comprising three 4,5-pinenobipyridine subunits connected through a mesityl spacer
      has been synthesized. Complexes of L with RuII and FeII have been prepared and
      characterised. NMR spectroscopy indicates that only one diastereoisomer is
      formed, and the CD spectra show that the complexes have the [capital Lambda]
      configuration on the metal centre. The X-ray crystal structure of the iron
      complex shows that in the octahedral complex, the ligand L coils around the metal
      and confirms the absolute configuration. The RuII and FeII compounds were also
      characterised by mass spectrometry, electronic absorption, and, in the case of
      Ru(II), fluorescence spectroscopy. The photostability of the ruthenium compound
      was checked by photochemical experiments.

PMID- 15252547
TI  - Redox state switching of transition metals by deprotonation of the tridentate
      ligand 2,6-bis(imidazol-2-yl)pyridine.
AB  - The chemistry of the ligand 1, 2,6-bis(imidazol-2-yl)pyridine with manganese,
      cobalt, nickel and ruthenium has been investigated. The ligand binds as a
      meridional tridentate ligand as shown by the crystal structures of
      [Mn(1)2](CF3SO3)2 x Et2O and [Ru(1)2](PF6)2 x 2CH3CN x H2O. The coordinated
      ligand is deprotonated in mildly basic solution, and this leads to a drop in the
      metal M(III)/M(II) reduction potential for cobalt and ruthenium of roughly 1.3 V.
      The crystal structure of Na2(PPN)[Co(1 - 2H)2]2(OH) x MeOH x 2H2O confirms the
      deprotonation and shows sodium to bind to the deprotonated nitrogen atoms. No
      stabilisation of the M(III) oxidation state was observed for nickel and
      manganese.

PMID- 15252548
TI  - Preparation and characterisation of palladium, platinum and manganese
      di(organo)carbene complexes from quinolinone and quinolinium precursors.
AB  - A series of palladium, platinum and manganese di(organo)carbene complexes have
      been prepared from 4-chloro-N-methylquinolinone by processes that involve
      alkylation before or after attachment to the metal unit; the nucleophilic
      heteroatoms are separated from the C-donor atom by three bonds.

PMID- 15252549
TI  - Speciation in the aqueous H+/H2VO4-/H2O2/picolinate system relevant to diabetes
      research.
AB  - A detailed study of the quaternary aqueous H+/H2VO4-/H2O2/picolinate (Pi-) system
      has been performed at 25 degrees C in 0.150 M Na(Cl) medium using quantitative 51
      V NMR (500 MHz) and potentiometric data (glass electrode). In the ternary
      H+/H2VO4-/Pi- system, six complexes have been found in the pH region 1-10. In the
      quaternary H+/H2VO4-/H2O2/Pi- system, eight additional complexes have been found.
      Generally, equilibria are fast in both systems. The rate of peroxide
      decomposition depends on the species in solution. Chemical shifts, compositions
      and formation constants for the species are given. Equilibrium conditions and the
      fit of the model to the experimental data are illustrated in distribution
      diagrams. Possible formation of mixed ligand species with imidazole, lactic acid
      and citric acid have been investigated and ruled out under the same experimental
      conditions. Structural proposals are given, based on 1)C NMR data and available
      crystal structures.

PMID- 15252550
TI  - Kinetics and mechanism of water substitution in the low-spin Fe(II) complex of 4
      octasulfophenylpyrazinoporphyrazine.
AB  - The substitution reaction of the axial-coordinated water by pyridine, pyrazine
      and 4-CN-pyridine in the low-spin Fe(II) complex of
      octasulfophenyltetrapyrazinoporphyrazine was studied. Kinetic and thermodynamic
      parameters for the different reaction steps of the process were determined. On
      the basis of NMR data and spectrophotometric titrations, a pronounced non
      equivalence of the two coordinated N-donor ligands was observed. The substitution
      of water by pyridine and 4-CN-pyridine is shown to include the formation of a
      precursor outer-sphere complex, whereas substitution by pyrazine follows a
      limiting dissociative mechanism.

PMID- 15252551
TI  - Synthesis of mono-amino-functionalised ferrocene, ferrocene salts and ferrocenium
      salts.
AB  - A number of mono-amino-functionalised ferrocenes, ferrocene salts and a mono
      amino-functionalised ferrocenium salt have been synthesised and characterised.
      This represents a novel method of accessing these important classes of molecules.
      In the cases of some of the ferrocene salts, there are some interesting
      structural features in the solid state. These include N-H...O and N-H...F
      hydrogen bonds.

PMID- 15252552
TI  - Self-assembly of novel macrocyclic aminomethylphosphines with hydrophobic
      intramolecular cavities.
AB  - Novel macroheterocyclic tetraphosphines, namely, 1,1',5,5'-bis(arylene)-bis(1,5
      diaza-3,7-diphosphacyclooctanes) 2-6, were obtained without the use of high
      dilution techniques or any matrix by the reaction of
      bis(hydroxymethyl)organylphosphines with primary aromatic diamines containing two
      p-phenylene fragments linked by various one-atom bridges in a molecular self
      assembly process. The structures of 4, 5 and 6 were investigated by X-ray crystal
      structure analyses. The macrocyclic cavities can be described as a truncated
      rhombohedral prism with side faces formed by phenylene rings and 1,5-diaza-3,7
      diphosphacyclooctanes in the truncated acute angles. In the crystals of these
      macrocycles, solvating DMF molecules are present, and a methyl group from each of
      two DMF molecules penetrates the macrocyclic cavities of 4 and 5 from either
      side, whereas only one disordered molecule of DMF penetrates the cavity of
      macrocycle 6. Different types of crystal packing are observed for the P-benzyl
      substituted compounds 4 and 5 and for the P-mesityl-substituted compound 6: for 4
      and 5 the formation of alternating layers containing the macrocycles and the DMF
      molecules is observed, in which the cavities of the macrocyclic molecules form
      channels and the DMF molecules are located in the centers of the channels; in the
      crystal of 6, six molecules are arranged around the 3 axis in the fashion of a
      six-bladed propeller.

PMID- 15252553
TI  - Dichlorobis(2-phenylazopyridine)ruthenium(II) complexes: characterisation,
      spectroscopic and structural properties of four isomers.
AB  - The didentate ligand 2-phenylazopyridine (azpy) can--in theory--give rise to five
      different isomeric complexes of the type [Ru(azpy)2Cl2], of which three have been
      known since 1980. The molecular structures of the cis-dichlorobis(2
      phenylazopyridine) ruthenium(II) complexes alpha-[Ru(azpy)2Cl2] and beta
      [Ru(azpy)2Cl2](in which the coordinating pyridine nitrogen atoms are in mutually
      trans and cis positions, respectively, whilst the azo nitrogen atoms are in
      mutually cis positions) were unambiguously determined in the early 1980s. The
      third isomer, gamma-[Ru(azpy)2Cl2], has for two decades, erroneously, been
      assumed to be the all-trans isomer. In a recent communication we have proven that
      for this gamma isomer the chloride ions are indeed in a trans geometry, but the
      pyridine nitrogen and azo nitrogen atoms of the two azpy ligands are in mutually
      cis geometries. In this paper the isolation of a fourth isomer is presented, the
      hitherto unknown delta-[Ru(azpy)2Cl2]. The isomeric structure of delta
      [Ru(azpy)2Cl2] has been determined by 1H-NMR spectroscopy and single-crystal X
      ray diffraction analysis, and is the all-trans isomer. The bis(azpy)
      ruthenium(II) isomers are of interest because of the pronounced cytotoxicity they
      exhibit against tumour cell lines and could be very useful in the search for
      structure-activity relationships of antitumour-active ruthenium complexes, as
      among the isomers there is a significant difference in activity. It is of
      paramount importance to have a good understanding of the structural and
      spectroscopic properties of these complexes, which in this paper are compared and
      discussed, with a particular emphasis on 1D and 2D 1H NMR spectroscopies.

PMID- 15252554
TI  - Preparation, electrochemical and spectral properties of N-methylated
      pyridylethynyl porphyrins.
AB  - A new series of electron-deficient porphyrins were prepared by attaching one or
      two N-methylated 2-, 3- or 4-pyridylethynyl groups to the 10,20-meso positions of
      (5,15-biphenylporphinato)zinc(II). Electrochemical studies showed significant
      changes in the reduction potentials of these porphyrins, and N-methyl-2
      pyridylethyne is the strongest electron-withdrawing substituent in the series. UV
      visible spectra demonstrated largely red-shifted absorptions, and N-methyl-4
      pyridylethyne has the greatest impact to the porphyrin absorptions.
      Electrochemical, UV-visible and EPR results concluded that porphyrins Zn2 and Zn6
      reversibly undergo two one-electron porphyrin-ring reductions to their anion
      radicals then dianions. The first reductions of porphyrins Zn1, Zn3, Zn4 and Zn5
      were irreversible one-electron transfer processes. The instability of these
      reduction products was suggested to result from the eletrophilic attacks at the
      substituents.

PMID- 15252555
TI  - Coordination features of ditopic oxa-azamacrocycles toward Ni(II) and Co(II).
      Dioxygen uptake by their dinuclear Co(II) complexes.
AB  - The coordination properties of the ditopic oxa-aza macrocycles L1-L3 toward
      Ni(II) and Co(II) have been investigated by means of potentiometric and UV-vis
      spectrophotometric measurements. L1-L3 contain two triamine and/or tetraamine
      chains separated by two dioxa chains and form both mono- and dinuclear complexes
      in aqueous solution. In the [ML]2+ complexes, the metal ion is coordinated by one
      of the two polyamine moieties, while the other does not participate in the
      coordination. In the dinuclear complexes each metal ion is coordinated, almost
      independently, to a single polyamine moiety. Under aerobic conditions the
      binuclear Co(II) complexes of the ligands L1-L3 are able to bind molecular
      oxygen, with a bridging coordination of O2 between the two metals.

PMID- 15252556
TI  - The reaction of GeCl4 with primary and secondary phosphines.
AB  - Reaction of GeCl4 and CyPH2 leads to a range of products from which crystals of
      [CyPH3]+[GeCl3]- have been obtained. The major intermediate in this reaction,
      Cy(H)PGeCl3, can be obtained as the dominant product only when an excess of GeCl4
      is used in the preparation. Similarly, crystals of [Ph2PH2]+[GeCl3]- have been
      obtained from reaction of Ph2PH and GeCl4(1 : 1). The structures of both primary
      and secondary phosphonium cations are reported. Aerosol-assisted and low-pressure
      chemical vapour deposition experiments using Cy(H)PGeCl3 as precursor lead to the
      deposition of thin films containing both germanium and phosphorus, contaminated
      with large amounts of oxygen. GeP has been identified as components of the film
      from bandgap measurements.

PMID- 15252557
TI  - Oxygen-17 NMR study of aqueous peroxotungstates.
AB  - Aqueous peroxotungstates have been studied from pH 0.5 to 9.0, over a range of
      peroxide concentrations. Although equilibria are not always established, many
      anions can be identified by 17O NMR because the ratio of deltaO(W
      anion)/deltaO(known Mo anion) is consistently 79 +/- 3%. They are [WO3(HO2)]-;
      [WO(OH)(O2)2]-; [WO(OH2)(O2)2]0; [W2O3(O2)4]2-; [W2O3(OH)(O2)4]3-; [W4O12(O2)2]4
      ; [W7O23(O2)]6- and [W7O22(O2)2]6-. Their pKa values, where measurable, are about
      2 units lower than the corresponding peroxomolybdates, e.g. 0.0 for
      [WO(OH2)(O2)2]0 and 8.0 for [W2O3(O2)4]2-. Other peroxotungstate species are also
      present but can only be broadly identified. These include Keggin structures with
      relatively low peroxo content, and a very unsymmetrical anion appearing at pH ca.
      7 that bears no obvious structural relationship to any species previously
      reported. The main product from the reaction of powdered W metal with 30% aqueous
      peroxide is provisionally identified as the symmetrical anion
      [W6O13(OH)2(OH2)2(O2)5]2-, although other minor species are also formed, probably
      having fewer peroxo substituents.

PMID- 15252558
TI  - Mono- and dinuclear molybdenum complexes with sterically demanding
      cycloheptatrienyl ligands.
AB  - Sterically demanding cycloheptatrienylium (tropylium) salts of the type (1,3,5
      C7H4R3)BF4 [R = t-Bu, (3a)BF4; R = SiMe3, (3b)BF4] have been prepared from the
      corresponding 1,3,5-trisubstituted benzene derivatives 1 by ring expansion with
      diazomethane followed by hydride abstraction with triphenylcarbenium
      tetrafluoroborate, (Ph3C)BF4. Complexation can be achieved by arene exchange and
      Mo(CO)3 group transfer employing [(eta6-p-xylene)Mo(CO)3] (4) to yield the
      cationic complexes (5)BF4. In refluxing mesitylene, [(eta7-C7H4t-Bu3)Mo(CO)3]BF4,
      (5a)BF4, undergoes CO substitution to furnish the mesitylene sandwich complex
      (6a)BF4. A cyclic voltammetric study reveals that this complex exhibits a
      reversible one-electron oxidation to the dicationic 17e complex 6a2+, which can
      also be accessed by chemical oxidation with AgBF4. On the contrary, the reduction
      of 6a+ is irreversible and does not yield a stable 19e complex 6a. To study the
      fate of the reduced 19e form, (5a)BF4 was treated with Na2Hg to
      diastereoselectively afford the C-C coupled bicycloheptatriene complex 7a.
      Paramagnetic, dinuclear complexes of the type [(eta7-C7H4R3)Mo(mu-Cl)3Mo(eta7
      C7H4R3)] (8) have been obtained from the reaction of (5)BF4 with Me3SiCl. These
      can be regarded as mixed-valence Mo(0)/Mo(+I) compounds with a metal-metal bond
      order of 0.5. Cyclic voltammetric studies reveal that both complexes 8a and 8b
      undergo reversible one-electron oxidation as well as reduction. Treatment with
      one equivalent of ferrocenium hexafluorophosphate leads to removal of the
      unpaired electron and formation of the diamagnetic complexes (8)PF6. Theoretical
      DFT calculations have been carried out to further elucidate the bonding in these
      systems. In addition, the X-ray crystal structures of (5b)BF4, (6a)BF4 x CH2Cl2,
      (6a)(BF4)2 x (acetone)2, 7a x CH2Cl2, 8a x 0.5C6H14, and (8a)PF6 x Et2O are
      reported.

PMID- 15252559
TI  - Crystal structures of dicarboxy-2,2'-bipyridyl complexes: the role of hydrogen
      bonding and stacking interactions.
AB  - The crystal structures of three complexes of dicarboxy-2,2'-bipyridyl ligands,
      5,5'-dicarboxy-2,2'-bipyridyl (1) and 4,4'-dicarboxy-2,2'-bipyridyl (2) are
      reported. [Rh(1H)3] shows two interpenetrating, homochiral rhombohedral networks
      linked by short carboxylate-carboxylic acid hydrogen bonds, in which each complex
      acts as a node for six hydrogen bonds. [Ru(1H2)(1H)2] forms only four such
      hydrogen bonds, leading to the formation of heterochiral chains held together by
      stacking between bipyridyls. [Co(2H)3] can in principle form six hydrogen bonds,
      but in practice forms only four in a layer structure where stacking interactions
      are important. This is attributed to differences in molecular shape.

PMID- 15252560
TI  - The structure of phosphine-functionalised silsesquioxane-based dendrimers: a
      molecular dynamics study.
AB  - Molecular dynamics modelling has been used to simulate the structures of
      phopshine-functionalised, silsesquioxane-based dendrimers whose excellent
      catalytic properties have been previously demonstrated. The effect of changing
      the chemical composition of the dendrimer branches is simulated. The results
      indicate that adding a methylene unit to a branch increases the overall size of
      the dendrimer but replacing a methylene unit with an oxygen atom decreases the
      size of the dendrimer. The size and shape of the dendrimers have also been
      simulated on changing the temperature and polarity of the solvent. The
      distribution of phosphine groups on the exterior has also been modelled and this
      suggests that all are available for bonding to catalytic metals in all the
      compounds.

PMID- 15252561
TI  - Hydrothermal synthesis and magnetic properties of novel Mn(II) and Zn(II)
      materials with thiolato-carboxylate donor ligand frameworks.
AB  - The hydrothermal reaction of thiosalicylic acid, (C(6)H(4)(CO(2)H)(SH)-1,2) with
      manganese(III) acetate leads to formation of the coordination solid
      [Mn(5)((C(6)H(4)(CO(2))(S)-1,2)(2))(4)(mu3-OH)2] (1) via a redox reaction, where
      resulting manganese(II) centres are coordinated by oxygen donor atoms and S-S
      disulfide bridge formation is simultaneously observed. Reaction of the same
      ligand under similar conditions with zinc(II) chloride yields the layered
      coordination solid [Zn(C(6)H(4)(CO(2))(S)-1,2)] (2). Hydrothermal treatment of
      manganese(III) acetate with 2-mercaptonicotinic acid, (NC(5)H(3)(SH)(CO(2)H)-2,3)
      was found to produce the 1-dimensional chain structure
      [Mn(2)((NC(5)H(3)(S)(CO(2))-2,3)(2))(2)(OH(2))(4)].4H(2)O (3) which also exhibits
      disulfide bridge formation and oxygen-only metal interactions. Compound 3 has
      been studied by thermogravimetric analysis and indicates sequential loss of
      lattice and coordinated water, prior to more comprehensive ligand fragmentation
      at elevated temperatures. The magnetic behaviour of 1 and 3 has been investigated
      and both exhibit antiferromagnetic interactions. The magnetic behaviour of 1 has
      been modelled as two corner-sharing isosceles triangles whilst 3 has been
      modelled as a 1-dimensional chain.

PMID- 15252562
TI  - Synthesis, crystal structure and hydroformylation activity of triphenylphosphite
      modified cobalt catalysts.
AB  - The dinuclear complex [Co(2)(CO)(6)[P(OPh)3]2] (2) has been synthesised and was
      fully characterised. The solid state structure revealed a trans diaxial geometry,
      no bridging carbonyls, and Co-Co and Co-P bond lengths of 2.6722(4) and 2.1224(4)
      Angstrom, respectively. Catalysed hydroformylation of 1-pentene with 2 was
      attempted at temperatures in the range 120 to 210 degrees C and pressures between
      34 and 80 bar. High pressure spectroscopy (HP-IR and HP-NMR) was used to detect
      hydride intermediates. High pressure infrared (HP-IR) studies revealed the
      formation of [HCo(CO)(3)P(OPh)3] (4) at ca. 110 degrees C, but at higher
      temperatures absorption bands corresponding to [HCo(CO)(4)]() were observed. The
      hydride intermediate 4 has also been synthesised and characterised. Upon
      increased ligand concentration, HP-IR studies showed the formation of new
      carbonyl absorption bands due to a higher substituted cobalt carbonyl complex
      [HCo(CO)(2)[P(OPh)3]2] (5), which is believed to be catalytically less active.
      Complex 5 has been synthesised independently and was fully characterised. A low
      temperature crystal structural study of 5 revealed a trigonal bipyramidal
      structure with a trans H-Co-CO arrangement and two equatorial phosphite ligands,
      the Co-P bond lengths being 2.1093(8) and 2.1076(8)[Angstrom], respectively.

PMID- 15252563
TI  - Polymeric networks of copper(II) using succinate and aromatic N-N donor ligands:
      synthesis, crystal structure, magnetic behaviour and the effect of weak
      interactions on their crystal packing.
AB  - Four succinato-bridged complexes of copper(II) have been synthesized. Complex 1,
      [Cu(2)(mu-OH(2))(2)L(bpy)(2)(NO(3))(2)](n) and 2, [Cu(2)(mu
      OH(2))(2)L(phen)(2)(NO(3))(2)](n)(bpy = 2,2[prime or minute]-bipyridine; phen =
      1,10-phenanthroline and LH(2)= succinic acid) exhibit 1D coordination polymer
      structures where both the nitrate ions are directly linked to the copper(ii)
      producing synthons in a 2D sheet. A novel 2D grid-like network,
      ([Cu(4)L(2)(bpy)(4)(H(2)O)(2)](ClO(4))(4)(H(2)O))n3, is obtained upon changing
      the nitrate by perchlorate anion in complex 1, where the channels are occupied by
      the anions. On changing the nitrate by tetrafluoroborate anion in complex 2, a
      novel octanuclear complex, [Cu(8)L(4)(phen)(12)](BF(4))(8).8H(2)O 4, is isolated.
      The coligand bpy and phen in these complexes show face-to-face (in 1,2,3,4) or
      edge-to-face (in 4 )pi-pi interactions forming the multidimensional
      supramolecular architectures. Interestingly, the appearance of edge-to-face pi-pi
      interactions in complex facilitates the formation of discrete octanuclear
      entities. Variable-temperature (300-2 K) magnetic measurements of complexes have
      been done. Complexes 1 and 2 show very weak antiferromagnetic (OOC-CH(2)-CH(2)
      COO) and ferromagnetic coupling (mu-H(2)O). Complex 3 also shows
      antiferromagnetic (syn-syn mu-OCO), and ferromagnetic coupling (mu-O of the -COO
      group). Complex 4 with two types (syn-syn and syn-anti) of binding modes of the
      carboxylate group shows strong antiferromagnetic interaction.

PMID- 15252564
TI  - New class of potent catalysts of O2.-dismutation. Mn(III) ortho
      methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins.
AB  - Three new Mn(III) porphyrin catalysts of O2.-dismutation (superoxide dismutase
      mimics), bearing ether oxygen atoms within their side chains, were synthesized
      and characterized: Mn(III) 5,10,15,20-tetrakis[N-(2-methoxyethyl)pyridinium-2
      yl]porphyrin (MnTMOE-2-PyP(5+)), Mn(III)5,10,15,20-tetrakis[N-methyl-N'-(2
      methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP(5+)) and Mn(III)
      5,10,15,20-tetrakis[N,N'-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2
      ImP(5+)). Their catalytic rate constants for O2.-dismutation (disproportionation)
      and the related metal-centered redox potentials vs. NHE are: log k(cat)= 8.04
      (E(1/2)=+251 mV) for MnTMOE-2-PyP(5+), log k(cat)= 7.98 (E(1/2)=+356 mV) for
      MnTM,MOE-2-ImP(5+) and log k(cat)= 7.59 (E(1/2)=+365 mV) for MnTDMOE-2-ImP(5+).
      The new porphyrins were compared to the previously described SOD mimics Mn(III)
      5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)), Mn(III)
      5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl)porphyrin (MnTnBu-2-PyP(5+)) and
      Mn(III) 5,10,15,20-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin (MnTDE-2
      ImP(5+)). MnTMOE-2-PyP(5+) has side chains of the same length and the same
      E(1/2), as MnTnBu-2-PyP(5+)(k(cat)= 7.25, E(1/2)=+ 254 mV), yet it is 6-fold more
      potent a catalyst of O2.-dismutation , presumably due to the presence of the
      ether oxygen. The log k(cat)vs. E(1/2) relationship for all Mn porphyrin-based
      SOD mimics thus far studied is discussed. None of the new compounds were toxic to
      Escherichia coli in the concentration range studied (up to 30 microM), and
      protected SOD-deficient E. coli in a concentration-dependent manner. At 3 microM
      levels, the MnTDMOE-2-ImP(5+), bearing an oxygen atom within each of the eight
      side chains, was the most effective and offered much higher protection than MnTE
      2-PyP(5+), while MnTDE-2-ImP(5+) was of very low efficacy.

PMID- 15252565
TI  - Electron transfer reactions between copper(II) porphyrin complexes and various
      oxidizing reagents in acetonitrile.
AB  - Homogeneous electron transfer reactions of the Cu(II) complexes of 5,10,15,20
      tetraphenylporphyrin (TPP) and 2,3,7,8,12,13,17,18-octaethylporphyrin (OEP) with
      various oxidizing reagents were spectrophotometrically investigated in
      acetonitrile. The reaction products were confirmed to be the pi-cation radicals
      of the corresponding Cu(II)-porphyrin complexes on the basis of the electronic
      spectra and the redox potentials of the complexes. The rate of the electron
      transfer reaction between the Cu(II)-porphyrin complex and solvated Cu(2+) was
      determined as a function of the water concentration under the pseudo first-order
      conditions where Cu(2+) is in large excess over the Cu(II)-porphyrin complex. The
      decrease in the pseudo first-order rate constant with increasing the water
      concentration was attributed to the stepwise displacement of acetonitrile in
      [Cu(AN)(6)](2+)(AN = acetonitrile) by water, and it was concluded that only the
      Cu(2+) species fully solvated by acetonitrile, [Cu(AN)(6)](2+), possesses
      sufficiently high redox potential for the oxidation of Cu(ii)-OEP and Cu(ii)-TPP.
      The reactions of the Cu(II)-porphyrin complexes with other oxidizing reagents
      such as [Ni(tacn)(2)](3+)(tacn = 1,4,7-triazacyclononane) and
      [Ru(bpy)(3)](3+)(bpy = 2,2'-bipyridine) were too fast to be followed by a
      conventional stopped-flow technique. Marcus cross relation for the outer-sphere
      electron transfer reaction was used to estimate the rate constants of the
      electron self-exchange reaction between Cu(II)-porphyrin and its pi-cation
      radical: log(k/M(-1) s(-1))= 9.5 +/- 0.5 for TPP and log(k/M(-1) s(-1))= 11.1 +/-
      0.5 for OEP at 25.0 degrees C. Such large electron self-exchange rate constants
      are typical for the porphyrin-centered redox reactions for which very small inner
      and outer-sphere reorganization energies are required.

PMID- 15252566
TI  - Ligand self-recognition in the stereoselective assembly of [2 + 2]
      metallomacrocycles from racemic chiral bisbipyridyl molecular clefts and
      zinc(II).
AB  - The synthesis of racemic and optically pure ligand L, in which two 6,6'
      disubstituted bipyridines are connected by methyleneoxy linkers to the molecular
      cleft dibenzobicyclo[b,f][3.3.1]nona-5a,6a-diene-6,12-dione, is reported. In the
      presence of 2 equivalents of zinc(ii) trifluoromethansulfonate (+/-)- undergoes
      slow reversible coordination over 24 h to form a pair of enantiomeric [2 + 2]
      metallomacrocycles, [Zn2(+)L2](OTf)(4) and [Zn2(-)L2](OTf)(4) respectively, that
      contain either two (+)-L ligands or two (-)-L ligands. This assignment was
      confirmed by independent studies with either (+)-L or (-)-L which formed the same
      complexes but at a significantly faster rate (3 h), and circular dichroism
      spectra of [Zn2(+)L2](OTf)(4) and [Zn2(-)L2](OTf)(4) which gave signals of the
      same intensity with the opposite sign. Treatment of (+/-)-L or optically pure L
      with copper(I) showed rapid formation of a mixture of oligomers as well as the [2
      + 2] metallomacrocycle. The complex Zn2L2(OTf)(4) exhibits slow exchange between
      two species on the NMR time scale at room temperature. The results are consistent
      with the formation of a library of metal complexes in which the zinc(ii) binds
      initially to the most accessible bipyridyl binding sites in (+/-)-. Equilibration
      over several hours results in self-recognition of enantiomeric ligands to form a
      pair of enantiomeric metallomacrocycles, which have been tentatively assigned as
      having the helical configuration. Slow exchange is attributed to the preference
      for both metal centres to adopt 6-coordinate geometries involving the linker
      oxygens, but are limited to exchanging 5-coordinate complexes due to the shape of
      the cleft and the short linker.

PMID- 15252567
TI  - Molecular structure of tris(dipivaloylmethanato)lutetium(iii) studied by gas
      electron diffraction and ab initio and DFT calculations.
AB  - Combined gas electron diffraction/mass spectrometry (GED/MS) was used to
      determine the molecular structure of tris(dipivaloylmethanato)lutetium(III),
      Lu(dpm)(3)(dpm = 2,2,6,6-tetramethyl-heptane-3,5-dionato). Up to about 520-570 K
      the vapour consisted only of molecules Lu(dpm)(3). The experimental data recorded
      at 408(5) K indicate that the molecules have D(3) symmetry. The bond distances
      (r(h1)) in the chelate ring are Lu-O 2.197(6) Angstrom, C-O 1.270(4) Angstrom and
      C-C 1.390(6) Angstrom . Theoretical computations at the HF and DFT levels with
      basis sets up to 6-311G* afford structures similar to those found experimentally,
      with a distorted LuO(6) antiprism.

PMID- 15252568
TI  - The molecular structures of pentaborane(9) with halogen substituents in apical
      and basal positions, determined by electron diffraction and theoretical
      calculations.
AB  - The molecular structures of 1-bromo-pentaborane(9) and 2-bromo-pentaborane(9) in
      the gas phase have been determined by electron diffraction and ab initio and DFT
      computational methods. Computational methods have also been applied to the fluoro
      and chloro analogues, to 1,2-dibromo-pentaborane(9), and to the parent
      unsubstituted borane. The electronic effects of halogen substitution on the
      borane cage are remarkably small, particularly for chlorine and bromine
      substituents, and steric effects are also minimal, even in the compound with two
      bromine atoms. The largest effects are (a) lengthening of B((base))-B((apex))
      bonds adjacent to the halogen in the 2-isomers, with an associated shortening of
      the opposite base-apex bond, (b) shortening of the B((base))-B((apex)) bond in
      the 1-fluoro compound, and (c) increase of the B((base))-B((apex))-F angle in 1-F
      B(5)H(8), but a decrease in this angle in the 2-bromo compounds.

PMID- 15252569
TI  - Synthesis, structure and electrochemistry of ferrocene-peptide macrocycles.
AB  - Redox active cyclopeptides Fc[CSA]2 (5), Fc[Gly-CSA]2 (6), Fc[Ala-CSA]2 (7),
      Fc[Val-CSA](2) and Fc[Leu-CSA]2 (9) (CSA = cysteamine) which are formed by the
      reaction of ferrocenedicarboxylic acid with peptide cystamines at high dilutions.
      These systems exhibit H-bonding involving the amide NH in solution as shown by
      their temperature dependent NMR spectra. With the exception of 5, the ferrocene
      macrocycles display intramolecular N...O cross-ring H-bonding in the solid state
      involving the amino acids proximal to the ferrocene.

PMID- 15252570
TI  - Synthesis of photo-luminescent Zn(II) Schiff base complexes and its derivative
      containing Pd(II) moiety.
AB  - An efficient method was developed for the preparation of a series of zinc Schiff
      base complexes. Introduction of a pyridyl group as a bridging unit as well as
      incorporation of ethynyl and electron-donating groups into the salicylidene
      moiety of these complexes moderately enhances the photoluminescence intensity and
      quantum yield. Electron-rich palladium groups possibly influence the
      photophysical character through the bridging C[triple bond]C bond. The crystal
      structure of the pyridine adduct of a salen Zn complex is determined by X-ray
      diffraction analysis.

PMID- 15252571
TI  - Bis-dinuclear (Cu-Gd)2 complexes with a probable helicate structure.
AB  - Two ligands have been designed to simultaneously favour complexation of 3d and 4f
      metal ions and the formation of helical structures. This synthetic strategy has
      allowed the isolation of two bis-dinuclear (Cu-Gd)(2) complexes
      [L(i)(2)Cu(2)Gd(2)(NO(3))(6)] derived from 3-alkoxysalicylaldehyde and 4,4'
      diaminodiphenylmethane. The magnetic data shows that both bis-dinuclear complexes
      behave as two practically independent (Cu-Gd) pairs, each presenting a
      ferromagnetic interaction (J= 4.6 cm(-1)). Very weak additional antiferromagnetic
      interactions, probably originating from intra- and/or intermolecular [small pi]
      stackings, are suggested by the decrease in chiMT below 8 K.

PMID- 15252572
TI  - Bis[1,1'-N,N'-(2-picolyl)aminomethyl]ferrocene as a redox sensor for transition
      metal ions.
AB  - The compound bis[1,1'-N,N'-(2-picolyl)aminomethyl]ferrocene, L(1), was
      synthesized. The protonation constants of this ligand and the stability constants
      of its complexes with Ni(2+), Cu(2+), Zn(2+), Cd(2+) and Pb(2+) were determined
      in aqueous solution by potentiometric methods at 25 degrees C and at ionic
      strength 0.10 mol dm(-3) in KNO(3). The compound L(1) forms only 1:1 (M:L)
      complexes with Pb(2+) and Cd(2+) while with Ni(2+) and Cu(2+) species of 2
      [ratio] 1 ratio were also found. The complexing behaviour of L(1) is regulated by
      the constraint imposed by the ferrocene in its backbone, leading to lower values
      of stability constants for complexes of the divalent first row transition metals
      when compared with related ligands. However, the differences in stability are
      smaller for the larger metal ions. The structure of the copper complex with L(1)
      was determined by single-crystal X-ray diffraction and shows that a species of
      2:2 ratio is formed. The two copper centres display distorted octahedral
      geometries and are linked through the two L(1) bridges at a long distance of
      8.781(10) Angstrom. The electrochemical behaviour of L(1) was studied in the
      presence of Ni(2+), Cu(2+), Zn(2+), Cd(2+) and Pb(2+), showing that upon
      complexation the ferrocene-ferrocenium half-wave potential shifts anodically in
      relation to that of the free ligand. The maximum electrochemical shift ([capital
      Delta]E(1/2)) of 268 mV was found in the presence of Pb(2+), followed by
      Cu(2+)(218 mV), Ni(2+)(152 mV), Zn(2+)(111 mV) and Cd(2+)(110 mV). Moreover, L(1)
      is able to electrochemically and selectively sense Cu(2+) in the presence of a
      large excess of the other transition metal cations studied.

PMID- 15252574
TI  - Bis(imino)phenoxide complexes of aluminium.
AB  - Reaction of Me(3)Al (one equivalent) with the bis(imino)phenol, [2,6-(ArNCH)(2)-4
      MeC(6)H(2)OH] (I)(Ar = 2,6-Pr(i)(2)C(6)H(3)) in toluene at ambient temperature
      yields the yellow complex [Me(2)Al[2,6-(ArNCH)(2)-4-MeC(6)H(2)O]](1). Interaction
      of two equivalents of Me(3)Al in refluxing toluene affords the red complex
      [(Me(2)Al)(2)[2-ArNCH(Me)-6-(ArNCH)-4-MeC(6)H(2)O]](2). Similar interaction (two
      equivalents, refluxing toluene) of MeAlCl(2) or (i)Bu(3)Al with [2,6-(ArNCH)(2)-4
      MeC(6)H(2)OH] affords [ClAl[2,6-(ArNCH)(2)-4-MeC(6)H(2)O](2)](3) or
      [(i)Bu(2)Al[2,6-(ArNCH)(2)-4-MeC(6)H(2)O]](4), respectively. Hydrolysis of 2
      readily affords the iminoaminophenol ligand [2-(ArN=CH)-6-ArNHCH(Me)-4
      MeC(6)H(2)OH](II), which reacts further with Me(3)Al to afford [Me(2)Al[2
      ArNCH(Me)-6-(ArNCH)-4-MeC(6)H(2)O]](5). An X-ray study on reveals bidentate imino
      alkoxide ligation about the distorted aluminium centre, whereas is a binuclear
      structure with tetrahedral aluminiums ligated by imino-alkoxide and amido
      alkoxide ligand fragments, respectively. For and bidentate imino-alkoxide
      ligation is observed.

PMID- 15252573
TI  - Synthesis, structure, redox, NLO and DNA interaction aspects of [((L'
      '")2RuII)3(mu3-L)]3+ and [(L')2RuII(NC5H4S-)]+[L3- = 1,3,5-triazine-2,4,6
      trithiolato, L'-'" = arylazopyridine].
AB  - The trinuclear complexes [(L'-'")2RuII)3(mu3-L)](ClO4)3, [1] (ClO4)3-[3](ClO4)3
      (L = trianionic form of 1,3,5-triazine-2,4,6-trithiol; N(p)C(5)H(4)N=N(a)
      C6H4(R), R = H (L'), m-Me (L"), p-Me (L'")) and the analogous mononuclear complex
      [(L')2RuII(NC5H4S-)]ClO4 [4] ClO4 were synthesized. Crystal structures of
      [1](ClO4)3 and [4]ClO4 were determined. [1](3+)-[3](3+) exhibit three successive
      oxidative couples corresponding to Ru(II)Ru(II)Ru(III)<==>Ru(II)Ru(II)Ru(II);
      Ru(II)Ru(III)Ru(III)<==>Ru(II)Ru(II)Ru(III);
      Ru(III)Ru(III)Ru(III)<==>Ru(II)Ru(III)Ru(III) where the mixed valent states are
      moderately coupled. The complexes display multiple reductions associated with the
      azo functions of the ancillary ligands (L'-'"). The energy of the Ru(II)-based
      lowest energy MLCT transitions (533-558 nm) involving the pi* level of azoimine
      chromophore of L'-'" varies depending on the nuclearity as well as substituents
      in the ligand framework and follows the order: [1](3+) > [2](3+) > [3](3+) >
      [4](+). The complexes exhibit reasonably high third-order non-linear optical
      properties with gamma= (0.90-2.45) [times] 10(-29) esu. The interactions of the
      trinuclear complexes [((L')2RuII)3(mu3-L)]3+[1]3+, [((bpy)2RuII)3((mu3-L)]3+[5]3+
      and [((phen)2RuII)3((mu3)-L)]3+[6]3+(bpy = 2,2'-bipyridine and phen = 1,10
      phenanthroline) with the circular and linear forms of p-Bluescript DNA show
      reduced ethidium bromide fluorescence on gel electrophoresis.

PMID- 15252575
TI  - The synthesis and structure of heteroleptic tris(diimine)ruthenium(II) complexes.
AB  - The reactions of bidentate diimine ligands (L2) with cationic
      bis(diimine)[Ru(L)(L1)(CO)Cl]+ complexes (L, L1, L2 are dissimilar diimine
      ligands), in the presence of trimethylamine-N-oxide (Me3NO) as a decarbonylation
      reagent, lead to the formation of heteroleptic tris(diimine) ruthenium(II)
      complexes, [Ru(L)(L1)(L2)]2+. Typically isolated as hexafluorophosphate or
      perchlorate salts, these complexes were characterised by UV-visible, infrared and
      mass spectroscopy, cyclic voltammetry, microanalyses and NMR spectroscopy. Single
      crystal X-ray studies have elucidated the structures of K[Ru(bpy)(phen)(4,4'
      Me(2)bpy)](PF(6))(3).1/2H(2)O, [Ru(bpy)(5,6-Me(2)phen)(Hdpa)](ClO(4))(2),
      [Ru(bpy)(phen)(5,6-Me(2)phen)](ClO(4))(2), [Ru(bpy)(5,6'-Me(2)phen)(4,4'
      Me(2)bpy)](PF(6))(2).EtOH, [Ru(4,4'-Me(2)bpy)(phen)(Hdpa)](PF(6))(2).MeOH and
      [Ru(bpy)(4,4'-Me(2)bpy)(Hdpa)](ClO(4))(2).1/2Hdpa (where Hdpa is di(2
      pyridyl)amine). A novel feature of the first complex is the presence of a
      dinuclear anionic adduct, [K(2)(PF(6))(6)](4-), in which the two potassium
      centres are bridged by two fluorides from different hexafluorophosphate ions
      forming a K(2)F(2) bridging unit and by two KFPFK bridging moieties.

PMID- 15252576
TI  - Reactions of 2,4-hexadiyne-1,6-diol with [H2Os3(CO)9(PR3)] clusters. Cyclization
      of the diyne and reversible exchange of the phosphine ligands between different
      positions of the "Os3C3" framework.
AB  - Reactions between unsaturated [H(2)Os(3)(CO)(9)(PR(3))] clusters (PR(3)= PPh(3),
      P(4-CF(3)-C(6)H(4))(3), PEt(3)) and 2,4-hexadiyne-1,6-diol have been studied. It
      was found that the diyne ligand easily reacts with all these complexes to give
      [HOs(3)(CO)8(PR3)-[mu3, eta1:eta3:eta1)-(CH(3)-C-C=CH-CH=C-O)]] complexes (V, VI
      and VII, respectively) containing the "Os3C3" pentagonal pyramid cluster
      framework. This structural pattern is formed through the diyne cyclization,
      dissociation of a CO ligand and eventual coordination of the cyclized organic
      moiety to the osmium triangle in the [mu3, eta1:eta3:eta1) manner. In the case of
      the PEt(3) substituted cluster the second hydride transfer onto the organic
      fragment occurs to afford the nonhydride [Os(3)(CO)(8)(PR3)[mu3), eta1:eta2:eta1)
      (CH(3)-CH-C=CH-CH=C-O)]] cluster, VIII, containing distorted pentagonal pyramid
      framework with a broken Os-C bond. Heating V, VI of VII and in hexane solutions
      results in formation of the regioisomers (Va, VIa and VIIa) with the phosphine
      ligand located at adjacent osmium atoms across the Os-Os bond bridged by the
      coordinated organic fragment. The most probable mechanism of the isomerization
      includes reversible phosphine migration between these metal centres. Solid-state
      structure of V, Va, VI, VIIa and VIII have been established by single crystal X
      ray diffraction. A general mechanistic scheme for the diyne ligand cyclization
      and cluster framework transformations is suggested and discussed.

PMID- 15252577
TI  - Biological inorganic and bioinorganic chemistry of neurodegeneration based on
      prion and Alzheimer diseases.
AB  - A change of the prion protein conformation results in a class of
      neurodegenerative diseases called the transmissible spongiform encephalopathies
      (like mad cow and Creutzfeld-Jakob diseases). The function of the normal prion
      protein is unknown, although much of recent research demonstrates the it may be a
      copper binding protein selective for Cu(II). Amyloid precursor protein (APP)
      releases the 39-42 amino acid peptide, a major constituent of the deposit in
      plaques of Alzheimer disease brain. Also APP is a metal binding protein,
      including copper ions. The link between copper and both proteins may provide
      insight into the role of metals in neurodegenerative pathologies.

PMID- 15252578
TI  - Electrochemical probing of ground state electronic interactions in polynuclear
      complexes of a new heteroditopic ligand.
AB  - The synthesis and electronic properties of dinuclear
      ([(bipy)2Ru(I)M(terpy)][PF6]4(bipy = 2,2'-bipyridine, terpy = 2,2':6',2''
      terpyridine; M = Ru, Os)) and trinuclear ([[(bipy)2Ru(I)]2M][PF6]6 M = Ru, Os,
      Fe, Co) complexes bridged by 4'-(2,2'-bipyridin-4-yl)-2,2':6',2''-terpyridine (I)
      have been investigated and are compared with those of mononuclear model
      complexes. The electrochemical analysis using cyclic voltammetry and differential
      pulse voltammetry reveals that there are no interactions in the ground state
      between adjacent metal centres. However, there is strong electronic communication
      between the 2,2'-bipyridine and 2,2':6',2''-terpyridine components of the
      bridging ligand. This conclusion is supported by a step-by-step reduction of the
      dinuclear and trinuclear complexes and the assignment of each electrochemical
      process to localised ligand sites within the didentate and terdentate domains.
      The investigation of the electronic absorption and emission spectra reveals an
      energy transfer in the excited state from the terminating bipy-bound metal
      centres to the central terpy-bound metal centre. This indicates that the bridge
      is able to facilitate energy transfer in the excited state between the metal
      centres despite the lack of interactions in the ground state.

PMID- 15252580
TI  - Co-ordination chemistry of amino pendant arm derivatives of 1,4,7
      triazacyclononane.
AB  - The binding properties of 1,4,7-triazacyclononane ([9]aneN3) to metal cations can
      be adapted through sequential functionalisation of the secondary amines with
      aminoethyl or aminopropyl pendant arms to generate ligands with increasing
      numbers of donor atoms. The new amino functionalised pendant arm derivative of
      1,4,7-triazacyclononane ([9]aneN3), L1, has been synthesised and its salt
      [H2L1]Cl2 characterised by X-ray diffraction. The protonation constants of the
      ligands L1-L4 having one, two or three aminoethyl or three aminopropyl pendant
      arms, respectively, on the [9]aneN3 framework, and the thermodynamic stabilities
      of their mononuclear complexes with CuII and ZnII have been investigated by
      potentiometric measurements in aqueous solutions. In order to discern the
      protonation sites of ligands L1-L4, 1H NMR spectroscopic studies were performed
      in D2O as a function of pH. While the stability constants of the CuII complexes
      increase on going from L1 to L2 and then decrease on going from L2 to L3 and L4,
      those for ZnII complexes increase from L1 to L3 and then decrease for L4. The X
      ray crystal structures of the complexes [Cu(L1)(Br)]Br, [Zn(L1)(NO3)]NO3,
      [Cu(L2)](ClO4)2, [Ni(L2)(MeCN)](BF4)2, [Zn(L4)](BF4)2.MeCN and
      [Mn(L4)](NO3)2.1/2H2O have been determined. In both [Cu(L1)(Br)]Br and
      [Zn(L1)(NO3)]NO3 the metal ion is five co-ordinate and bound by four N-donors of
      the macrocyclic ligand and by one of the two counter-anions. The crystal
      structures of [Cu(L2)](ClO4)2 and [Ni(L2)(MeCN)](BF4)2 show the metal centre in
      slightly distorted square-based pyramidal and octahedral geometry, respectively,
      with a MeCN molecule completing the co-ordination sphere around NiII in the
      latter. In both [Zn(L4)](BF4)2.MeCN and [Mn(L4)](NO3)2.1/2H2O the metal ion is
      bound by all six N-donors of the macrocyclic ligand in a distorted octahedral
      geometry. Interestingly, and in agreement with the solution studies and with the
      marked preference of CuII to assume a square-based pyramidal geometry with these
      types of ligands, the reaction of L4 with one equivalent of Cu(BF4)2.4H2O in MeOH
      at room temperature yields a square-based pyramidal five co-ordinate CuII complex
      [Cu(L6)](BF4)2 where one of the three propylamino pendant arms of the starting
      ligand has been cleaved to give L6.

PMID- 15252579
TI  - A bifurcated pathway of oxygen atom transfer reactions from a monooxo
      molybdenum(VI) complex under electrospray ionisation mass spectrometric
      conditions.
AB  - A stable molybdenum(V) complex, LMoOCl2(where L is hydrotris(3,5
      dimethylpyrazolyl)borate), has been oxidized under mass spectrometric conditions.
      The oxidized species reacts with tertiary phosphines and the products have been
      detected by mass spectrometry. The product distribution has been followed by
      isotope labeling experiments, and energy dependent electrospray mass
      spectrometry. These experiments reveal not only oxygen atom transfer but also
      loss of a chlorine atom from the resulting species.

PMID- 15252581
TI  - Lanthanide complexes of new nonadentate imino-phosphonate ligands derived from
      1,4,7-triazacyclononane: synthesis, structural characterisation and NMR studies.
AB  - The polyamino ligand 1,4,7-tris(2-aminoethyl)-1,4,7-triazacyclononane (1) has
      been used to synthesise two new ligands by Schiff-base condensation with methyl
      sodium acetyl phosphonate to give ligand L and methyl sodium 4-methoxybenzoyl
      phosphonate to give ligand L1 in the presence of lanthanide ion as templating
      agent to form the complexes [Ln(L)] and [Ln(L1)](Ln = Y, La, Gd, Yb). Both
      ligands L and L1 have nine donor atoms comprising three amine and three imine N
      donors and three phosphonate O-donors and form Ln(III) complexes in which the
      three pendant arms of the ligands wrap around the nine-coordinate Ln(III)
      centres. Complexes with Y(III), La(III), Gd(III) and Yb(III) have been
      synthesised and the complexes [Y(L)], [Gd(L)] and [Gd(L1)] have been structurally
      characterised. In all the complexes the coordination polyhedron about the
      lanthanide centre is slightly distorted tricapped trigonal prismatic with the two
      triangular faces of the prism formed by the macrocyclic N-donors and the
      phosphonate O-donors. Interestingly, given the three chiral phosphorus centres
      present in [Ln(L)] and [Ln(L1)] complexes, the three crystal structures reported
      show the presence of only one diastereomer of the four possible. 1H, 13C and 31P
      NMR spectroscopic studies on diamagnetic [Y(L)] and [La(L)] and on paramagnetic
      [Yb(L)] complexes indicate the presence in solution of all the four different
      diastereomers in varying proportions. The stability of complexes [Y(L)] and
      [Y(L1)] in D2O in both neutral and acidic media, and the relaxivity of the
      Gd(III) complexes, have also been investigated.

PMID- 15252582
TI  - Conformational and stereochemical flexibility in cadmium(II) complexes of aza
      thioether macrocycles.
AB  - The synthesis and crystal structures of four CdII macrocyclic complexes
      containing mixed N-, O- and S-donors, [Cd(NO3)2([12]aneN2S2)] (1),
      [Cd(NO3)2([12]aneNS3)] (2), [Cd(NO3)2([15]aneNO2S2)] (3) and
      [Cd(NO3)([15]aneN2O2S)]NO3 (4), are presented. The metal ion is coordinated
      outside of the macrocyclic cavity in the complexes of the smaller macrocycles
      ([12]aneN2S2 and [12]aneNS3) while the flexibility of the larger macrocycles in
      and allows very different conformations to be adopted with a 'butterfly' geometry
      in and a flattened geometry in. No correlation between the number of sulfur
      donors and Cd-S bond distance in these types of complexes is observed, although
      the number and binding mode of the nitrato ligands is determined by the
      conformation and binding mode of the macrocycle. The position of the nitrato
      ligand also influences, through steric conflicts with the macrocyclic donor
      atoms, the bond distances in both ligand systems.

PMID- 15252583
TI  - Early-late, mixed-metal compounds supported by amidophosphine ligands.
AB  - The sequential syntheses, structural characterisation and reactivity studies of a
      series of discrete early-late mixed-metal complexes supported by the unique
      amidophosphine ligand m-(But2CH)N(C6H4)PPh2L1 are described. This ligand was
      synthesised using a Schiff-base/ButLi protocol and the resultant lithium salt
      LiL1 found to adopt a tetrameric structure in the solid state in which both two
      coordinate N-Li-N and eta6:eta6-arylLi metallocene bonding motifs are present.
      Reaction between HL1 and labile Pt(II) and Pd(II) chlorides formed MCl2(HL1)2
      complexes 4 (M = Pt) and 5 (M = Pd) in which a weak N-H...pi(aryl) hydrogen
      bonding interaction was identified in the solid-state structure of 4. These
      compounds were found to be inert to transamination and protonolysis reactions
      with Ti amides and alkyls; instead, stepwise alkyl transfer from Ti to Pt,
      resulting in Pt(CH2SiMe3)2(HL1)2 6 was observed. Access to mixed-metal complexes
      was achieved using an early-metal-first approach. Reaction between the
      metalloligand TiCl2(L1)2 and labile Group 10 and group 9 compounds resulted in
      the formation of TiCl2(mu-L1)2PtCl2 8, TiCl2(mu-L1)2PtMe2 9, TiCl2(mu-L1)2PdCl2
      10, TiCl2(mu-L1)2NiBr2 11, and [TiCl2(mu-L1)2RhCl(CO)]2 12. In the solid state,
      the Group 4/10 compounds 8, 9 and 10 adopt similar structures that exhibit both
      intramolecular But2C-H...Cl-Ti hydrogen bonding and arylNP pi-stacking
      interactions; this hydrogen-bonding interaction is conserved in solution. Unlike
      the above Group 4/10 complexes, the Ti-Rh complex 12 adopts a tetranuclear
      structure in the solid state that is stabilised by similar hydrogen-bonding and
      pi-stacking interactions. The Group 4/10 complexes were assessed as catalysts for
      olefin polymerisation and cross-coupling reactions. In combination with MAO, the
      mixed-metal complexes 8 and 10 were poor ethylene polymerisation catalysts and
      resulted in polymers of both high molecular weight and polydispersity. The Ti-Ni
      complex 11 formed oligomeric material only, while the mononuclear Ti
      metalloligand TiCl2(L1)2 gave the best results, showing low activity (6.14 kg
      mol(-1) bar(-1) h(-1)) and moderate polydispersity (12). The Ti-Pd complex 10 was
      assessed in arylamination and Suzuki-Miyaura reactions. While little or no
      catalytic activity was observed in arylamination reactions, 10 was found to
      effect Suzuki coupling between activated aryl bromides and phenylboronic acid at
      80 degrees C. Unlike with TiCl2(L1)2, reactions between 8 and the reducing agents
      C8K or Mg led to intractable mixtures. However, the cyclic voltammetry of both
      compounds indicated that a reversible one-electron reduction process occurs at a
      similar potential (ca. -0.7 V) and was assigned to the formation of the
      monohalides TiCl(L1)2 and TiCl(mu-L1)2PtCl2. The reactivity of the metallocage
      TiCl(mu-L3)3Pt was also investigated. While reduction reactions were
      unsuccessful, the metallocage reacted with CO to form the Ti-Pt carbonyl, TiCl(mu
      L3)3Pt(CO) 13. The X-ray crystal structure of 13 revealed that accommodation of
      CO at the Pt centre has caused the cage expansion and loss of agostic aryl-H...Pt
      interactions. Furthermore, reaction of TiCl(mu-L3)3Pt with excess MeI resulted in
      the formation of the Ti(IV)-Pt(II) complex trans-TiCl2(mu-L3)2(kappa1
      L3MeI)Pt(Me)I.

PMID- 15252584
TI  - Reduction reactions of a 1,3,5-triphosphabenzene.
AB  - The reactions of the triphosphabenzene, 1,3,5-P3C3But3, with LiMH4, M = Al or Ga,
      lead to the triphosphabicyclo[3.1.0]hexanediyl metallate complexes,
      [[[Li(OEt2)][MH2(P3C3But3H2)]]2], which give exo- and endo-isomers of a
      triphosphabicyclo[3.1.0]hexane, P3C3But3H4 upon quenching. The related reaction
      of [AlH3(NMe3)] with 1,3,5-P3C3But3 affords three identifiable products, viz. a
      triphosphabicyclo[3.1.0]hexenyl complex, [AlH2(P3C3But3H)(NMe3)], and two
      triphosphabicyclo[3.1.0]hexanediyl complexes, [AlH(P3C3But3H2)(NMe3)] and
      [Al2H4(P3C3But3H2)(NMe3)]. In contrast, the reactions of 1,3,5-P3C3But3 with
      either [GaH3(quin)], quin = quinuclidine, or Me3SnH lead only to the
      triphosphabicyclo[3.1.0]hexenyl complexes, [GaH2(P3C3But3H)(quin)] and
      [Me3Sn(P3C3But3H)]. Quenching of the former affords a
      triphosphabicyclo[3.1.0]hexene, P3C3But3H2, while quenching the latter gives its
      triphosphacyclohexa-1,4-diene valence isomer. Treatment of 1,3,5-P3C3But3 with
      "GaI" yields a GaI3 complex of the triphosphahexa-1,4-diene, [GaI3(P3C3But3H2)],
      whilst treatment with the anionic Ga(I) heterocycle, [:Ga[N(Ar)C(H)]2]-, Ar =
      C6H3Pri2-2,6, affords the known diphospholyl anion, [1,3-P2C3But3]- via a P
      abstraction from the triphosphabenzene. Finally, reaction of the 1,3,5
      triphosphacyclohexane, [P(OEt)C(H)(But)]3, with thionyl chloride yields the
      unusual lambda5, lambda5, lambda5-1,3,5-triphosphacyclohexane,
      [P(O)(Cl)C(H)(But)]2[P(OEt)(S)C(H)(But)]. Suggestions as to the mechanisms of a
      number of these reduction reactions are made and the crystal structures of seven
      compounds are reported.

PMID- 15252585
TI  - Structures of the radical P[N(SiMe3)2](NPri2), its dimer, cation and chloro
      derivative.
AB  - Treatment of PCl[N(SiMe3)2](NPri2) (1) with potassium-graphite in thf afforded
      the colourless, crystalline diphosphine [P[N(SiMe3)2](NPri2)]2 (2) in good yield.
      Sublimation of 2 in vacuo yielded the yellow phosphinyl radical
      P[N(SiMe3)2](NPri2) (3), which upon cooling reverted to 2; the latter in C6D6 at
      298 K was a mixture of rac and meso diastereoisomers. The yellow, crystalline
      phosphenium salt [P[N(SiMe3)2](NPri2)][AlCl4] (4) was obtained from 1 and
      1/2Al2Cl6 in CH2Cl2. By single-crystal X-ray diffraction (XRD) the structures of
      the known compound 1 and of 2 and 4 were determined. The structure of the radical
      3, formed by the thermal homolytic dissociation of the diphosphine 2, was
      determined in the gas phase by electron diffraction (GED), utilising data from
      UMP2/6-31+G*ab initio calculations. The model of the molecule in the GED
      structure analysis was described by a set of internal coordinates and an initial
      set of Cartesian coordinates from ab initio calculations, facilitating the
      structure analysis. The experimental data were found to be consistent with the
      presence of a single conformer of the radical in the gas phase. The computed
      standard homolytic dissociation enthalpy of the P-P bond in the corresponding
      diphosphine 2, corrected for BSSE, 54 kJ mol(-1), is substantially reduced
      compared to the dissociation enthalpy of tetramethyldiphosphine by the
      reorganisation energies of the fragments that form upon dissociation. The
      intrinsic energy content of the P-P bond in the diphosphine 2 was estimated to be
      286 kJ mol(-1), in agreement with the results of previous work on a series of
      crowded diphosphines.

PMID- 15252586
TI  - Organotin and organogermanium linkers for simple, direct functionalization of
      polyoxotungstates.
AB  - Fifteen Keggin-anion-derived polytungstates [TW11O39[MCH2CH2X]]n- (T = Si, Ge,
      Ga; M = Sn, Ge; X = COOH, COOCH3, CONH2, CN; n = 5, 6) were prepared in aqueous
      or aqueous-organic solution from the corresponding lacunary polytungstates and
      trichlorotin and -germanium precursors, and were isolated as caesium salts. The
      derivatized polytungstates were characterized by elemental analysis, multinuclear
      NMR spectroscopy, and cyclic voltammetry; they are stable in aqueous solution to
      pH 6-7. NMR spectroscopy revealed the presence of a second (beta1 or beta3)
      isomer in the tungstogallate derivatives. Acid hydrolysis of the ester and
      nitrile derivatives could be achieved without decomposition of the polytungstate
      moieties, and esterification and amidation of the carboxylate functions was
      straightforward using standard coupling techniques, e.g. the formation, isolation
      and characterization of [SiW11O39[Ge(CH2)2CONHCH2COOCH3]]5- from glycine methyl
      ester. Since the Cl3MCH2CH2X precursors are readily accessible by
      hydrostannation/germanation reactions with the corresponding alkenes, novel
      coupled polytungstates, such as [(SiW11O39GeCH2CH2COOCH2)4C]20- from
      pentaerythritol tetraacrylate, can also be prepared.

PMID- 15252587
TI  - Governing the oxidative addition of iodine to gold(I) complexes by ligand tuning.
AB  - While several gold(I) complexes of the type (L)AuX (X = Cl, Br) are known to
      undergo oxidative addition of elemental chlorine and bromine (X2), respectively,
      to give the corresponding gold(III) complexes (L)AuX3, the addition of iodine to
      (iodo)gold(I) compounds is strongly ligand-dependent, suggesting a crucial
      threshold in the oxidation potentials. A systematic investigation of this
      particular oxidative addition of iodine using a large series of tertiary
      phosphines as ligands L has shown that both electronic and steric effects
      influence the course of the reaction. The reactions were followed by 31P NMR
      spectroscopy and the products crystallized from dichloromethane-pentane
      solutions. Complexes with small triakylphosphines (PMe3, PEt3) are readily
      oxidized, while those with more bulky ligands (PiPr3, PtBu3) are not. With L
      taken from the triarylphosphine series [PPh3, P(2-Tol)3, P(3-Tol3), P(4-Tol)3] no
      oxidation takes place at all, but mixed alkyl/aryl-phosphines [PMenPh(3-n)]
      induce oxidation for n = 3 and 2, but not for n = 1 and 0. However, in cases
      where no oxidation of the gold atoms is observed, the synthons may crystallize as
      adducts with molecular iodine of the polyiodide type instead, which have an
      iodine rich stoichiometry. This fact explains inconsistent reports in the
      literature. The metal atoms in (L)AuI coordination compounds with L representing
      a tri(heteroaryl)phosphine [P(2-C4H3E)3, E = O, S], a phosphite [P(OR)3] or a
      trialkenylphosphine [PVi3] are all not subject to oxidative addition of iodine.
      The dinuclear complex of the ditertiary phosphine Ph2PCH2PPh2, (dppm)(AuI)2,
      gives an iodine adduct (without oxidation of the metal atoms), but with 1,2
      Ph2P(C6H4)PPh2(dppbe) an ionic complex [(dppbe)AuI2]+I3- with a chelated
      gold(III) centre is obtained. The gold(I) bromide complexes with tertiary
      phosphines are readily oxidized by bromine to give the corresponding gold(III)
      tribromide complexes, as demonstrated for (BzMePhP)AuBr and (Ph3P)AuBr. With
      (dppm)(AuBr)2 the primary product with mixed oxidation states was also isolated:
      (dppm)AuBr(AuBr3). The crystal structures of the following representative
      examples and reference compounds have been determined: (Me3P)AuI3, (Me2PhP)AuI3,
      (iPr3P)AuI.1.5I2, (Ph3P)AuI.I2, [[(2-Tol)3P]AuI]2.I2, [(2-Tol)3P]AuI,
      (dppm)(AuX)2 (with X = Br, I), (dppm)AuBr(AuBr3) and [(dppbe)AuI2]+I3-. The
      structures are discussed focusing on the steric effects. It appears that e.g. the
      reluctance of (Ph3P)AuI to add I2 is an electronic effect, while that of
      (iPr3P)AuI has its origin in the steric influence of the ligand.

PMID- 15252588
TI  - Carboxylic acid functionalized cobalt(III) cyclen complexes for catalytic
      hydrolysis of phosphodiester bonds.
AB  - 4-(1,4,7,10-Tetraazacyclotetradec-1-yl)methylbenzoic acid (cycmba, 1) has been
      synthesized, as a step towards the eventual development of sequence-specific
      hydrolytic complexes. A cobalt(III) complex of 1, [Co(cycmba)Cl2]Cl.1.5H2O
      (.1.5H2O) was found to be active against both an activated phosphodiester
      compound, bis(nitrophenyl)phosphate (BNPP), and supercoiled DNA. The presence of
      the benzoate group depresses the rate of hydrolysis of the ligand-Co(III) system
      at neutral pH, as confirmed by the kinetics results of a methyl ester analog. The
      ability of (2.1.5H2O) to bind to solid substrates and remain active was also
      demonstrated by attachment of the molecule to agarose beads.

PMID- 15252589
TI  - Cationic lanthanide complexes of neutral tripodal N,O ligands: enthalpy versus
      entropy-driven podate formation in water.
AB  - The cationic lanthanide complexes of two neutral tripodal N,O ligands, tpa
      (tris[(2-pyridyl)methyl]amine) and tpaam (tris[6-((2-N,N
      diethylcarbamoyl)pyridyl)methyl]amine) are studied in water. The analysis of the
      proton lanthanide induced NMR shifts indicate that there is no abrupt structural
      change in the middle of the rare-earth series. Unexpectedly, the formation
      constant values of the lanthanide podates of tpaam and tpa in D2O at 298 K are
      similar, suggesting that the addition of the three amide groups to the ligand tpa
      does not lead to any increase in stability of the lanthanide complexes of tpaam
      in respect to tpa, even though the amide groups are coordinated to the metal in
      aqueous solution. The measurement of the enthalpy and entropy changes of the
      complexation reactions shows that the two similar ligands tpa and tpaam have
      different driving forces for lanthanide complexation. Indeed, the formation of
      tpa podates benefits from an exothermic enthalpy change associated with a small
      entropy change, whereas the complexation reaction with tpaam is clearly entropy
      driven though opposed by a positive enthalpy change. The hydration states of the
      europium complexes were measured by luminescence and show the coordination of 4-5
      water ligands in [Eu(tpa)]3+ whereas there are only 2 in [Eu(tpaam)]3+. Therefore
      the heptadentate ligand tpaam releases the translational entropy of more water
      molecules than does the tetradentate ligand tpa.

PMID- 15252590
TI  - Reactions of thiosemicarbazones derived from beta-keto amides and beta-keto
      esters with Zn(II) and Cd(II) acetates: influence of metal, substitution, reagent
      ratio and temperature on metal-induced cyclization.
AB  - Zinc(II) and cadmium(II) acetates were reacted in methanol under various
      experimental conditions with thiosemicarbazones derived from beta-keto amides or
      beta-keto esters (HTSC). Some of these reactions afforded thiosemicarbazonate
      complexes [M(TSC)2] with IR and NMR spectra compatible with N,S-coordination, but
      most gave complexes [ML2], where HL is a substituted 2,5-dihydro-5-oxo-1H
      pyrazole-1-carbothioamide resulting from cyclization of the HTSC. Some of these
      pyrazolonates and two of the HL ligands were studied by X-ray diffractometry, and
      their structures are discussed. Surprisingly, the reactions of zinc(II) acetate
      with HTSC in 1:1 mol ratio usually gave a third, previously unreported type of
      complex with a dideprotonated ligand, [Zn(L-H)], which was also formed when
      [ZnL2] and Zn(OAc)2 interacted at room temperature in 1:1 mol ratio. These L-H
      complexes are highly insoluble in all common solvents, which hinders their
      characterization but suggests that they are polymeric in nature.

PMID- 15252591
TI  - Multinuclear (1H, 31P and 195Pt) NMR study and dynamical analysis of binuclear mu
      hydrido mu-carbonyl Pt(I) cations with chelating diphosphines.
AB  - The dynamic behaviour of the binuclear mu-hydrido mu-carbonyl cations with
      chelating diphosphines, [Pt2(P-P)2(mu-H)(mu-CO)]+ [P-P = dppe, 1, dppp, 2, and
      dppb, 3] have been investigated by multinuclear (1H, 31P and 195Pt) variable
      temperature NMR spectroscopy. The 195Pt and 1H results are consistent with
      intramolecular mutual exchange of the P atoms with respect to the bridging
      ligands in all of the complexes 1-3. A detailed dynamical analysis carried out on
      complexes 2 and 3 shows that the dynamical process exchanges the P atoms within a
      single diphosphino ligand, and excludes the simultaneous P atom exchange in both
      ligands. The bite of the diphosphino ligands affects the rate of this process in
      the order 3 > 2 > 1. The process follows an activation law with deltaH++ = 67 and
      60 kJ mol(-1) for 2 and 3, respectively, so that P-Pt bond breaking should not be
      involved. The positive activation entropy (17-19 J K(-1) mol(-1)) hints at a
      mechanism where the intermediate(s) have a less ordered structure than that of
      the stable complex. In accordance with the NMR results, two reactivity
      experiments provided further evidence of the intramolecular nature of the
      observed dynamics and exclude any equilibration path via Pt-P and/or Pt-Pt bond
      breaking. On these grounds, a mechanism involving rotation about a Pt-Pt bond
      could be proposed.

PMID- 15252592
TI  - Synergistic effect of Ni(II) and Co(II) ions on the sulfite induced autoxidation
      of Cu(II)/tetraglycine complex.
AB  - The synergistic effect of Ni(II) and Co(II) on the sulfite induced autoxidation
      of Cu(II)/tetraglycine was investigated spectrophotometrically at 25.0 degrees C,
      pH = 9.0, 1 x 10(-5) mol dm(-3) < or = [S(IV)] < or = 8 x 10(-5) mol dm(-3),
      [Cu(II)]= 1 x 10(-3) mol dm(-3), 1 x 10(-6) mol dm(-3) < or = [Ni(II)] or
      [Co(II)] < or = 1 x 10(-4) mol dm(-3), [O2] approximately 2.5 x 10(-4) mol dm(
      3), and 0.1 mol dm(-3) ionic strength. In the absence of added nickel(II) or
      cobalt(II), the kinetic traces of Cu(III)G4 formation show a large induction
      period (about 3 h). The addition of trace amounts of Ni(II) or Co(II) increases
      the reaction rate significantly and the induction period drastically decreases
      (less than 0.5 s). The effectiveness of Cu(III)G4 formation becomes much higher.
      The metal ion in the trivalent oxidation state rapidly oxidizes SO3(2-) to SO3*-,
      which reacts with oxygen to produce SO5*-. The strongly generated oxidants
      oxidize Cu(II)G4 to Cu(III).

PMID- 15252593
TI  - N-benzoylimido complexes of palladium. Synthesis, structural characterisation and
      structure-reactivity relationship.
AB  - Benzoyl azides, ArC(O)N3, 2, (Ar = phenyl or substituted phenyl), react with
      [Pd2Cl2(dppm)2], 1, [dppm = bis(diphenylphosphino)methane] with the formation of
      novel [Pd2Cl2(mu-NC(O)Ar)(dppm)2], 3, benzoylnitrene complexes that were
      structurally characterised by multinuclear magnetic resonance and IR spectroscopy
      and, in several instances, by single crystal X-ray diffraction. As shown by
      crystallographic studies, the C2P4Pd2 rings adopt extended twist-boat
      conformations with methylene groups bending towards the bridging benzoylimido
      moieties. X-ray diffraction studies have revealed the chiral nature of the imido
      complexes, the chiral element being the propeller-like C2P4Pd2 ring. Structural
      data accumulated on complexes 3 such as short C-N distances (1.32 A), elongated
      C=O bonds (1.30 A) as well as the outstandingly high barrier to internal rotation
      around the N-C(O) linkage (88.3 kJ mol(-1)) are in line with extensive ppi-ppi
      interaction between the bridging nitrogen and the carbonyl carbon atoms.
      Theoretical calculations indicate an electron shift from the dimer towards the
      apical nitrogen atom, which, in turn, facilitates the donation of electrons
      towards the carbonyl moiety. To elucidate the structure-reactivity relationship
      of benzoyl azides towards 1, crystallographic and solution IR spectroscopic
      studies were carried out on a series of para-substituted benzoyl azides. The
      reaction obeys the Hammett equation. The large positive value of the reaction
      constant indicates that the azides act as electrophiles in the reaction studied.
      The enhanced reactivity of 2-nitrobenzoyl azide has been attributed to a
      decreased conjugation of the phenyl and carbonyl moieties in this reagent.

PMID- 15252594
TI  - Heteroscorpionate ligands based on bis(pyrazol-1-yl)methane: design and
      coordination chemistry.
AB  - Scorpionates represent one of the most versatile types of tridentate ligand that
      can coordinate to a wide variety of elements, e.g. from early to late transition
      metals, and the coordination chemistry of these systems has developed greatly in
      recent years. This Perspective gives an account of studies on the following
      aspects: (1) the preparative methods for a new class of heteroscorpionate
      [RR'C(pz)2] ligand derived from bis(pyrazol-1-yl)methane and (2) the description
      of metal complexes containing these ligands, examples of which incorporate a
      range of different metals from the Periodic Table.

PMID- 15252595
TI  - Structural, magnetic and DFT studies of a hydroxide-bridged [Cr8] wheel.
AB  - Structural, magnetic and theoretical studies of an octanuclear chromium(III)
      wheel are reported, containing hydroxide and pivalate bridges.

PMID- 15252596
TI  - Synthesis and characterisation of macrocyclic palladium(II)-sodium(I) complexes:
      generation of an unusual metal-mediated electron delocalisation.
AB  - Reaction of sodium perchlorate-crown ether derivative (LH2) complex
      [Na2LH2](ClO4)2 (1) with palladium acetate afforded two related compounds of
      macrocyclic palladium(II)-sodium(I) dimeric tetranuclear complexes, [Pd2Na2L2(mu
      OH2)2](ClO4)2(CH2Cl2)3 (2) and [Pd2Na2(L-)2](CH3CN)2(C3H6O)2 (3) and their
      structures were characterised by IR, NMR, mass and X-ray analysis; the latter was
      revealed as an unusual metal-mediated electron delocalised complex.

PMID- 15252597
TI  - The thermal and light induced spin transition in [FeL2](BF4)2 (L = 2,6-dipyrazol
      1-yl-4-hydroxymethylpyridine).
AB  - This communication presents the crystal structures of the high spin state at 300
      K, the low spin state at 30 K and the metastable high spin state after
      irradiation at 30 K and an estimate of the critical LIESST temperature of
      [FeL2](BF4)2 which is shown to undergo a spin transition at 271 K.

PMID- 15252598
TI  - Well-defined indium(III)N-heterocyclic carbene complexes with triflate ligands:
      structural models for the In(OTf)3 catalyst.
AB  - Reaction of 1,3-dimesitylimidazolium chloride [IMesH]Cl with InMe3 results in
      (IMes)InMe2Cl, which on treatment with one equivalent of TMS-OTf affords
      (IMes)InMe2(OTf), which can be converted to the bistriflate complex
      (IMes)In(Me)(OTf)2 on addition of HOTf.

PMID- 15252599
TI  - Macropolyhedral boron-containing cluster chemistry. Ligand-induced two-electron
      variations of intercluster bonding intimacy. Structures of nineteen-vertex [(eta5
      C5Me5)HIrB18H19(PMe2Ph)] and the related carbene complex [(eta5
      C5Me5)HIrB18H19[C(NHMe)2]].
AB  - Addition of PMe2Ph to fused-cluster syn-[(eta5-C5Me5)IrB18H20] 1 to give [(eta5
      C5Me5)HIrB18H19(PMe2Ph)] 3 entails a diminution in the degree of intimacy of the
      intercluster fusion, rather than retention of inter-subcluster binding intimacy
      and a nido-->arachno conversion of the character of either of the subclusters.
      Reaction with MeNC gives [(eta5-C5Me5)HIrB18H19[C(NHMe)2]] 4 which has a similar
      structure, but with the ligand now being the carbene [:C(NHMe)2], resulting from
      a reductive assembly reaction involving two MeNC residues and the loss of a
      carbon atom.

PMID- 15252600
TI  - Photoinduced Ru-Yb energy transfer and sensitised near-IR luminescence in a
      coordination polymer containing co-crystallised [Ru(bipy)(CN)4]2- and Yb(III)
      units.
AB  - Co-crystallisation of the anionic cyanometallate chromophore [Ru(bipy)(CN)4]2-
      with Yb(III) provides coordination polymers or oligomers containing Ru-CN-Yb
      bridges; in [K(H2O)4][Yb(H2O)6][Ru(bipy)(CN)4]2.5H2O Ru-->Yb energy-transfer (k >
      5 x 10(6) s(-1)) results in partial quenching of the Ru-based luminescence and
      sensitised near-IR luminescence from the Yb(III) unit.

PMID- 15252601
TI  - Solid state coordination chemistry: structural consequences of variations in
      tether length in the oxovanadium-copper-bisterpy-[O3P(CH2)nPO3]4- system, n= 1-6
      (bisterpy = 2,2':4',4'':2'',2'''-quarterpyridyl-6',6''-di-2-pyridine).
AB  - Hydrothermal reactions of Na3VO4, an appropriate Cu(II) source, bisterpy and an
      organodiphosphonate, H2O3P(CH2)nPO3H2 (n = 1-6) yielded a family of materials of
      the type [Cu2(bisterpy)]4+/VxOy(n-)/[O3P(CH2)nPO3]4-. This family of bimetallic
      oxides is characterized by an unusual structural diversity. The oxides
      [[Cu2(bisterpy)]V2O4[O3PCH2PO3H]2] (1),
      [[Cu2(bisterpy)(H2O)]VO2[O3P(CH2)3PO3][HO3P(CH2)3PO3H2]] (4) and
      [[Cu2(bisterpy)]V2O4[O3P(CH2)6PO3H]2].2H2O (7.2H2O) are one-dimensional, while
      [[Cu2(bisterpy)(H2O)2]V2O4[O3P(CH2)2PO3][HO3P(CH2)2PO3H]2] (2),
      [[Cu2(bisterpy)]V4O8[O3P(CH23PO3]2].4H2O (3.4H2O) and
      [[Cu2(bisterpy)]V2O4(OH)2[O3P(CH2)4PO3]].4H2O (5.4H2O) are two-dimensional. The
      V(IV) oxide [[Cu2(bisterpy)]V4O4[O3P(CH2)5PO3H]4].7.3H2O (6.7.3H2O) provides a
      relatively unusual example of a three-dimensional bimetallic oxide phosphonate.
      The structures reveal a variety of V/P/O substructures as building blocks.

PMID- 15252602
TI  - Nickel and iron complexes with oxazoline- or pyridine-phosphonite ligands;
      synthesis, structure and application for the catalytic oligomerisation of
      ethylene.
AB  - The bis(oxazolinyl)phenylphosphonite ligand (bis(4,4-dimethyl-2-(1-hydroxy-1
      methylethyl)-4,5-dihydrooxazole)phenylphosphonite, NOPONMe2)) and the new
      pyridine-phosphonite ligand (2-ethyl(1'-methyl-1-hydroxy)pyridine-6H
      dibenz[c,e][1,2]oxaphosphorin) have been used for the preparation of the
      mononuclear complexes [NiCl2(NOPONMe2)] 18 and [NiCl2(6)2] 19, respectively,
      which catalyze the oligomerisation of ethylene with activities up to 57300 mol
      C2H4 mol Ni(-1) h(-1) (19 in the presence of only 6 equivalents of AlEtCl2). The
      selectivities for C4 dimers were as high as 90% (18 in the presence of only 2
      equivalents of AlEtCl2) with selectivities for 1-butene of 21-22% of the C4
      fraction. In the presence of 400 or 800 equivalents of MAO as cocatalyst, complex
      19 yielded turnover frequencies of 7400 mol C2H4 mol Ni(-1) h(-1) and 13200 mol
      C2H4 mol Ni(-1) h(-1), respectively. The selectivities for 1-butene and ethylene
      dimers were similar to those obtained with AlEtCl2. The fact that 19 with a
      cyclic phosphonite moiety leads to higher activities and selectivities than 18
      which contains an acyclic phosphonite group underlines the importance of the
      ligand on the catalytic properties of its metal complex. An unprecedented
      dinuclear iron complex [FeCl2(4,4-dimethyl-2-[(1-hydroxy-1-methyl)ethyl]-4,5
      dihydrooxazolate)]2 20 was also obtained which contains two pentacoordinated
      metal centers coordinated by a bridging-chelating oxazoline-alcoholate. Complexes
      18-20 are paramagnetic in solution, as determined by the Evans method.

PMID- 15252603
TI  - Binding sites on the outside of metallo-supramolecular architectures; engineering
      coordination polymers from discrete architectures.
AB  - Aggregation of metallo-supramolecular architectures through additional
      coordination is explored by introducing metal-binding units onto the outside of
      the supramolecular architectures. This is achieved within the framework of our
      imine-based approach to supramolecular architecture, by replacing the
      pyridylimine units with pyrazylketimine units. An advantage of the design is that
      it retains the ease-of-synthesis which characterises our imine-based approach.
      Silver(I) complexes of three pyrazylketimine ligand systems are described. The
      complexes demonstrate that introducing pyrazine donor units does indeed allow
      higher-order assembly of the distinct supramolecular architectures into
      engineered coordination polymers. Two distinct types of aggregation are observed.
      In the first, the donors on the outside of one architecture bind to the metals of
      another to link the units into a polymeric array. In the second type, the donors
      on the outside of the architectures bind to separate metal centres which are
      themselves not part of the architectures, and these separate metal centres link
      the units to form the macromolecular array. The weaker donor nature of the
      pyrazine nitrogens (compared to pyridine) also introduces an additional element
      into the design; higher coordination numbers are favoured and this can lead to
      arrays with higher connectivity than those observed in the discrete pyridylimine
      architectures.

PMID- 15252604
TI  - Theoretical study of reaction pathways for the rhodium phosphine-catalysed
      borylation of C-H bonds with pinacolborane.
AB  - The reaction mechanism of the rhodium-phosphine catalysed borylation of methyl
      substituted arenes using pinacolborane (HBpin) has been investigated
      theoretically using DFT calculations at the B3PW91 level. Factors affecting
      selectivity for benzylic vs. aromatic C-H bond activation have been examined. It
      was found that [Rh(PR3)2(H)] is the active species which oxidatively adds the C-H
      bond leading to an eta3-benzyl complex which is the key to determining the
      unusual benzylic regioselectivity observed experimentally for this catalyst
      system. Subsequent reaction with HBpin leads to a [Rh(PR3)2(eta3
      benzyl)(H)(Bpin)] complex from which B-C reductive elimination provides product
      and regenerates the catalyst. The electrophilic nature of the boryl ligand
      assists in the reductive elimination process. In contrast to Ir(L)2(boryl)3-based
      catalysts, for which Ir(III)-Ir(V) cycles have been proposed, the Rh(I)-Rh(III)
      cycle is operating with the system addressed herein.

PMID- 15252605
TI  - Mononucleotide recognition by cyclic trinuclear palladium(II) complexes
      containing 4,7-phenanthroline N,N bridges.
AB  - Reaction of [(dach)Pd(NO3)2] entities (dach = (R,R)-1,2-diaminocyclohexane, (S,S)
      1,2-diaminocyclohexane) and 4,7-phenanthroline (phen) providing, respectively, 90
      and 120 degrees bond angles, leads to the formation of two novel positively
      charged homochiral cyclic trinuclear metallacalix[3]arene species [((R,R)-1,2
      diaminocyclohexane)Pd(phen)]3(NO3)6 (2a) and [((S,S)-1,2
      diaminocyclohexane)Pd(phen)]3(NO3)6 (2b). These species have been characterised
      by 1)H NMR and X-ray diffraction methods (2b), showing that they possess
      accessible cavities suited for supramolecular recognition processes. We prove,
      indeed, from 1H NMR studies the inclusion of mononucleotides inside the cavity of
      the trinuclear species [(ethylenediamino)Pd(phen)]3(6+) (1), [((R,R)-1,2
      diaminocyclohexane)Pd(phen)]3(6+) (2a) and [((S,S)-1,2
      diaminocyclohexane)Pd(phen)]3(6+) (2b) in aqueous solution. Association constants
      (K(ass)) range from 85 +/- 6 M(-1) for the interaction between
      [(ethylenediamine)Pd(phen)]3(6+) and adenosine monophosphate to 37 +/- 4 M(-1)
      for the interaction between [(1,2-diaminocyclohexane)Pd(phen)]3(6+) and thymidine
      monophosphate. We invoke the synergy of electrostatic, anion-pi and pi-pi
      interactions to explain the recognition of mononucleotides inside the cavity of
      the metallacalix[3]arenes.

PMID- 15252606
TI  - Synthetic and structural experiments on yttrium, cerium and magnesium
      trimethylsilylmethyls and their reaction products with nitriles; with a note on
      two cerium beta-diketiminates.
AB  - The yttrium, cerium and magnesium bis(trimethylsilyl)methyls [Ln[CH(SiMe3)2]3][Ln
      = Y (1), Ce (2)], and the known compound Mg[[CH(SiMe3)2]2 (C) and [Mg(mu
      Br)[CH(SiMe3)2](OEt2)]2 (D) formed the crystalline nitrile adducts [1(NCBut)2]
      (5), [2(NCPh)] (6), [C(NCR)2][R = But (8), Ph (9), C6H3Me2-2,6 (10)] and [Mg(mu
      Br)[CH(SiMe3)2](NCR)]2 [R = But (11), Ph (12), C6H3Me2-2,6 (13)], rather than
      beta-diketiminato-metal insertion products. The beta-diketiminato-cerium complex
      [Ce[(N(SiMe3)C(C6H4But-4))2CH][N(SiMe3)2]2] (16) was obtained from
      [Ce[N(SiMe3)2]3] and the beta-diketimine H[[N(SiMe3)C(C6H4But-4)]2CH]]. The
      cerium alkyl 2 and [Ln[CH(SiMe3)(SiMe2OMe)]3][Ln = Y (3), Ce (4)] were obtained
      from the appropriate lithium alkyl precursor and [Ce(OC6H2But2-2,6-Me-4)3] or
      LnCl3, respectively. Heating complex 3 with benzonitrile in toluene afforded 2,2
      dimethyl-4,6-diphenyl-5-trimethylsilyl-1,3-diaza-2-silahexa-1,3-diene (7), a
      member of a new class of heterocycles. The X-ray structures of the crystalline
      compounds, D, [Mg[CH(SiMe3)2]2(OEt2)2], the known [Ce(Cl)[(N(SiMe3)C(Ph))2CH]2]
      (E) and 16 are reported. The cerium alkyl (like 1) has one close Ce...C contact
      for each ligand, attributed to a gamma-C-Ce agostic interaction. The Ln alkyls
      and have a trigonal prismatic arrangement of the chelating ligands (each of the
      same chirality at Calpha) around the metal. In an arene solution at 313 K exists
      as two isomers, as evident from detailed NMR spectroscopic experiments.

PMID- 15252607
TI  - Synthesis, structure, and ethene polymerisation catalysis of 1- or 2-silyl
      substituted bis[indenyl]zirconium(IV) dichlorides.
AB  - The systematic syntheses of 1- and 2-substituted silylindenes, with a wide
      variety of substitution patterns on the silyl moiety, and their corresponding
      zirconocene dichlorides are presented. The rac- and meso-diastereomers of the 1
      substituted zirconocene dichlorides can in most cases be separated. Instable
      zirconocenes were observed for certain substitution patterns. Two of the obtained
      zirconocene dichlorides, bis[2-(dimethylsilyl)indenyl]zirconium dichloride (4a)
      and bis[2-(trimethylsilyl)indenyl]zirconium dichloride (4b), were characterised
      by single crystal X-ray diffraction. On the basis of DFT results, the two
      compounds are geometrically similar, i.e. the additional methyl group on the
      silyl moiety only affects the conformational energy profile. Differences in their
      catalyst performance in the homopolymerisation studies with ethane are thus
      attributed to conformational control. For the remaining complexes, sterically
      less demanding silyl groups seem to be favoured with respect to the catalyst
      performance. All the 2-isomers have lower polymerisation activities than the
      unsubstituted bis[indenyl]zirconium dichloride/MAO system. Curiously, the rac
      bis[1-(dimethylphenylsilyl)indenyl]zirconium dichloride/MAO system is found to be
      the most active catalyst in ethene homopolymerisations.

PMID- 15252608
TI  - A novel dicationic phenoxaphosphino-modified Xantphos-type ligand: a ligand for
      highly active and selective, biphasic, rhodium catalysed hydroformylation in
      ionic liquids.
AB  - A highly active and regioselective catalyst obtained from a novel dicationic
      ligand (1) and Rh(CO)2(acac) for hydroformylation of 1-hexene and 1-octene in
      ionic liquids is reported. Optimisation studies of various reaction parameters
      led to an unprecedentedly active (TOFs > 6200 mol mol(-1) h(-1), T= 100 degrees
      C), selective (l/b ratios > 40) and stable hydroformylation procedure. No
      catalyst leaching (Rh-loss < 0.07% of initial rhodium intake, P-loss < 0.4% of
      the initial phosphorus intake) or losses in performance could be measured during
      1-octene hydroformylation recycle experiments in 1-butyl-3-methylimidazolium
      hexafluorophosphate. At low catalyst loadings activities and regioselectivities
      competitive with one-phase catalysis in conventional solvents were observed. At
      high catalyst loadings the system is extremely stable and has a long shelf-life
      as a result of the formation of stable, if inactive rhodium dimers.

PMID- 15252609
TI  - Cyclam-based dendrimers as ligands for lanthanide ions.
AB  - We have investigated the complexation of lanthanide ions (Nd3+, Eu3+, Gd3+, Tb3+,
      Dy3+) with three cyclam-based ligands (cyclam = 1,4,8,11
      tetraazacyclotetradecane), namely 1,4,8,11-tetrakis(naphthylmethyl)cyclam (1),
      and two dendrimers consisting of a cyclam core appended with four
      dimethoxybenzene and eight naphthyl units (2) and twelve dimethoxybenzene and
      sixteen naphthyl units (3). In the free ligands the fluorescence of the naphthyl
      units is strongly quenched by exciplex formation with the cyclam nitrogens.
      Complexation with the metal ions prevents exciplex formation and revives the
      intense naphthyl fluorescence. Fluorescence and NMR titration experiments have
      revealed the formation of complexes with different metal/ligand stoichiometries
      in the case of 1, 2 and 3. Surprisingly, the large dendrimer 3 gives rise to a
      stable [M(3)3]3+ species. Energy transfer from the lowest singlet and triplet
      excited states of the peripheral naphthyl units to the lower lying excited states
      of Nd3+, Eu3+, Tb3+, Dy3+ coordinated to the cyclam core does not take place.

PMID- 15252610
TI  - Preparation, structures and some reactions of novel diynyl complexes of iron and
      ruthenium.
AB  - Reactions between HC triple bond CC triple bond CSiMe3 and several ruthenium
      halide precursors have given the complexes Ru(C triple bond CC triple bond
      CSiMe3)(L2)Cp'[Cp'= Cp, L = CO (1), PPh3 (2); Cp' = Cp*, L2= dppe (3)]. Proto
      desilylation of 2 and 3 have given unsubstituted buta-1,3-diyn-1-yl complexes
      Ru(C triple bond CC triple bond CH)(L2)Cp'[Cp'= Cp, L = PPh3 (5); Cp'= Cp*, L2 =
      dppe (6)]. Replacement of H in 5 or 6 with Au(PR3) groups was achieved in
      reactions with AuCl(PR3) in the presence of KN(SiMe3)2 to give Ru(C triple bond
      CC triple bond CAu(PR3)](L2)Cp'[Cp' = Cp, L = PPh3, R = Ph (7); Cp' = Cp*, L2=
      dppe, R = Ph (8), tol (9)]. The asymmetrically end-capped [Cp(Ph3P)2Ru]C triple
      bond CC triple bond C[Ru(dppe)Cp*] (10) was obtained from Ru(C triple bond CC
      triple bond CH)(dppe)Cp* and RuCl(PPh3)2Cp. Single-crystal X-ray structural
      determinations of and are reported, with a comparative determination of the
      structure of Fe(C triple bond CC triple bond CSiMe3)(dppe)Cp* (4), and those of a
      fifth polymorph of [Ru(PPh3)2Cp]2(mu-C triple bond CC triple bond C) (12), and
      [Ru(dppe)Cp]2(mu-C triple bond CC triple bond C) (13).

PMID- 15252611
TI  - Unsuccessful/successful attempts to produce penta(heteroaryl)-phosphoranes/
      arsoranes R5E (E = P, As; R = 2-furyl, 2-thienyl).
AB  - Tri(2-thienyl)phosphine (1) has been transformed into chlorotri(2
      thienyl)phosphonium chloride (3) in the reaction with hexachloroethane, into
      tetra(2-thienyl)phosphonium bromide (4) in a NiBr2-catalyzed quaternization with
      2-bromothiophene, and into the p-tolylsulfonyliminotri(2-thienyl)phosphorane (6)
      using "chloramine T". Attempts to generate the homoleptic penta(2
      thienyl)phosphorane (2-C4H3S)5P (5) by treating 3, 4, 6 or the known
      (PhO)3P=NSO2C6H4-2-Me (9) with 2-thienyllithium were unsuccessful. Tri(2
      furyl)phosphine (2) was converted into the related imine 7, but the reaction of 7
      or of 9 with 2-furyllithium failed to give (2-C4H3O)5P (8). It was only with the
      strained phosphorane Ph(C12H8)P=NSO2C6H4-4-Me (C12H8= 2,2'-biphenylylene) (10)
      that with 2-C4H3OLi the corresponding phosphorane Ph(C12H8)P(C4H3O-2)2 (11) could
      be obtained (31P NMR: delta-106.7 ppm). In the arsenic series, tri(2-thienyl)-
      and tri(2-furyl)arsine (12, 13) were converted into the tosylimino compounds (14,
      15) and successfully transformed into the homoleptic arsoranes with 2-C4H3E-Li:
      penta(2-thienyl)- (16) and penta(2-furyl)-arsorane (17) are stable colourless
      crystalline solids, the NMR spectra of which indicate rapid pseudo-rotation in
      solution. The single crystal structure analysis of 17 shows an only slightly
      distorted trigonal-bipyramidal configuration. In crystals of the phosphine 2 and
      the arsine 13 the molecules have a propeller configuration with approximate C3v
      symmetry for the former, but Cs symmetry for the latter. The crystal structures
      of the precursors or intermediates 3, 4, 6, 9, and 10 have also been determined.

PMID- 15252612
TI  - Synthesis and structural characterization of silanethiolato complexes having tert
      butyldimethylsilyl and trimethylsilyl groups.
AB  - Treatment of cyclotrisilathiane (Me2SiS)3 with 3 equiv. of RLi (R = Me, But) in
      hexane-Et2O afforded the lithium silanethiolates LiSSiMe2R, and the tmeda adduct
      [(tmeda)LiSSiMe2But]2 1 (tmeda =N,N,N',N'-tetramethylethylenediamine) was
      isolated in the case of R = But. Reaction of Fe(CH3CN)2(CF3SO3)2, CoCl2, and
      [Cu(CH3CN)4](PF6) with 1 gave rise to the silanethiolato complexes
      M(SSiMe2But)2(tmeda)(M = Fe 2, Co 3), and [Cu(SSiMe2But)]4 4, respectively.
      Complexes (C5H5)2Ti(SSiMe2R)2(R = Me 5, But 6) and Ni(SSiMe2R)2(dppe)[R = Me 7,
      But 8; dppe = 1,2-bis(diphenylphosphino)ethane] were prepared from treatments of
      (C5H5)2TiCl2 and NiCl2(dppe) with the corresponding lithium silanethiolates.
      Complex 7 readily reacted with (C5H5)TiCl3 to produce the Ti-Ni heterobimetallic
      compound (C5H5)TiCl(mu-S)2Ni(dppe) 9, in which silicon-sulfur bond cleavage took
      place. Characterization of all compounds through spectroscopic techniques and
      elemental analyses are also described. X-Ray structural data for compounds 1 and
      3-9 are reported.

PMID- 15252613
TI  - Cobalt tris(mercaptoimidazolyl)borate complexes: synthetic studies and the
      structure of the first cobaltaboratrane.
AB  - The paramagnetic complexes (TmtBu)CoX (X = Cl, Br, I) have been readily prepared
      and structurally characterized and provide a convenient entry into cobalt(II)
      tris(mercaptoimidazolyl)borate chemistry. A number of derivatives, including
      mononuclear triphenylphosphine adducts [(TmtBu)Co(PPh3)]X and dinuclear compounds
      [Co2(TmtBu)2X]Y, have been prepared in order to ascertain whether cobalt is a
      reliable surrogate for zinc in biological systems, particularly in sulfur-rich
      coordination environments. The structure of the first cobaltaboratrane is also
      reported.

PMID- 15252614
TI  - Synthesis and crystal structure of uranium(IV) complexes with compartmental
      Schiff bases: from mononuclear species to tri- and tetranuclear clusters.
AB  - Treatment of U(acac)4 with the hexadentate Schiff base H2L(i) gave the [UL(i)2]
      complexes 1-4 [H2L1=N,N'-bis(3-methoxysalicylidene)-2-methyl-1,2-propanediamine,
      H2L2=N,N'-bis(3-methoxysalicylidene)-1,2-phenylenediamine, H2L3=N,N'-bis(3
      methoxysalicylidene)-2-aminobenzylamine and H2L4=N,N'-bis(3-methoxysalicylidene)
      2,2-dimethyl-1,3-propanediamine for 1-4, respectively]. The [U(L(i))(acac)2]
      compounds could not be isolated because of their ready disproportionation into
      [UL(i)2] and U(acac)4. Compounds 2 and 4 adopt a meridional configuration in the
      solid state and in solution, while exists in solution as the two equilibrating
      meridional and sandwich isomers and crystallizes in the meridional isomeric form.
      Reaction of U(acac)4 with H4L5 afforded the expected compound [U(H2L5)(acac)2]
      (5) [H4L5=N,N'-bis(3-hydroxysalicylidene)-2-methyl-1,2-propanediamine] but, in
      the presence of H4L6 and H4L7, U(acac)4 was transformed in a serendipitous and
      reproducible manner into the tri- and tetranuclear U(IV) complexes
      [U3(L6)(HL6)2(acac)2] (6) and [U4(HL7)4(H2L7)2] (7) [H4L6=N,N'-bis(3
      hydroxysalicylidene)-1,2-phenylenediamine and H4L7=N,N'-bis(3
      hydroxysalicylidene)-2-aminobenzylamine]. The crystal structures of 6.3thf and
      7.5thf show the assembling role of the Schiff-base ligands.

PMID- 15252615
TI  - Perfluoroalkylphosphine coordination chemistry of platinum: synthesis of
      (C2F5)2PPh and (C2F5)PPh2 complexes of platinum(II).
AB  - A 1:1 addition of Ph2PCl to an ethereal solution of C2F5Li (formed from the
      reaction of BuLi with C2F5Cl) yields Ph2P(C2F5)(abbreviated pfepp) (1). The
      introduction of a fluoroethyl group results in a phosphine with electronic
      characteristics that approximate phosphites, bridging the electronic gap between
      traditional donor phosphine ligands and more electrophilic phosphine ligands like
      PhP(C2F5)2 (2). The pfepp ligand 1 is isolated as a high boiling liquid, which
      crystallizes upon standing at room temperature in an inert atmosphere. A series
      of Pt(II) complexes of the type trans-L2PtCl2 (L = pfepp 3; PhP(C2F5)2 4) have
      been prepared and structurally characterized by multinuclear NMR, IR and X-ray
      crystallography. The crystal structure of is the first example of a structurally
      characterized monodentate phosphine with a pentafluoroethyl pendant group.

PMID- 15252616
TI  - Quantifying the relative contribution of hydrogen bonding and hydrophobic
      environments, and coordinating groups, in the zinc(II)-water acidity by synthetic
      modelling chemistry.
AB  - Ligands derived from the tripodal N4 ligand tris(pyridylmethyl)amine ((pyCH2)3N,
      tpa) of general formula (6-RNHpyCH2)nN(CH2py)(3-n)(R = H, n= 1-3 L(1-3); R =
      neopentyl, n= 1-3 L'(1-3)) were used to elucidate and quantify the magnitude of
      the effects exerted by hydrogen bonding and hydrophobic environments in the zinc
      water acidity of their complexes. The pKa of the zinc-bound water molecule of
      [(L(1-3))Zn(OH2)]2+ and [(L'(1-3))Zn(OH2)]2+ 1'-3' was determined by
      potentiometric pH titrations in water (1-3) or water-ethanol (1:1) (1'-3'). The
      zinc(II) water acidity gradually increases as the number of -NH2 hydrogen bonding
      groups adjacent to the water molecule increases. Thus, the zinc-bound water of
      [(L3)Zn(OH2)]2+ and [(tpa)Zn(OH2)]2+ deprotonate with pKa values of 6.0 and 8.0,
      respectively. The pKa of the water molecule, however, is only raised from 8.0 in
      [(tpa)Zn(OH2)]2+ to 9.1 in [(bpg)Zn(OH2)]+ (bpa =(pyCH2)2N(CH2COO-)). Moreover,
      the acidity of the zinc-bound water of several of the five-coordinate zinc(II)
      complexes with the hydrogen bonding groups is greater than that of four
      coordinate [((12)aneN3)Zn(OH2)]2+ (pKa = 7.0). This result shows that the
      magnitude of the effect exerted by the hydrogen bonding groups can be larger than
      that induced by changing one neutral by one anionic ligand, and/or even by
      changing the coordination number of the zinc(II) centre. The X-ray structure of
      [(L'2)Zn(OH)]ClO4 2' and [(L'3)Zn(OH)]ClO4.CH3CN 3'.CH3CN is reported, and show
      the neopentylamino groups forming N-H...O hydrogen bonds with the zinc-bound
      hydroxide. Although, which have hydrogen bonding and hydrophobic groups, have a
      zinc-bound water more acidic than [(tpa)Zn(OH2)]2+, their pKa is not always lower
      than that of 1-3. This result suggests that a hydrogen bonding microenvironment
      may be more effective than a hydrophobic one to increase the zinc-water acidity.

PMID- 15252617
TI  - Various forms of linear dipyridyls in discrete rectangles, dinuclear rods, and
      one-dimensional networks containing (eta5
      pentamethylcyclopentadienyl)rhodium(III).
AB  - [Cp*Rh(eta1-NO3)(eta2-NO3)] (1) reacted with pyrazine (pyz) to give a dinuclear
      complex [Cp*Rh(eta1-NO3)(mu-pyz)(0.5)]2.CH2Cl2(3.CH2Cl2). Tetranuclear rectangles
      of the type [Cp*Rh(eta1,mu-X)(mu-L)(0.5)]4(OTf)4(4a: X = N3, L = bpy; 4b: X = N3,
      L = bpe; 4c: X = NCO, L = bpy) were prepared from [Cp*Rh(H2O)3](OTf)2 (2), a
      pseudo-halide (Me3SiN3 or Me3SiNCO), and a linear dipyridyl [4,4'-bipyridine
      (bpy) or trans-1,2-bis(4-pyridyl)ethylene (bpe)] by self-assembly through one-pot
      synthesis at room temperature. Treating complex with NH4SCN and dipyridyl led to
      the formation of dinuclear rods, [Cp*Rh(eta1-SCN)3]2(LH2) (5a: L = bpy; 5b: L =
      bpe), in which two Cp*Rh(eta1-SCN)3 units are connected by the diprotonated
      dipyridyl (LH2(2+)) through N(+)-H...N hydrogen bonds. Reactions of complex 2
      with 1-(trimethylsilyl)imidazole (TMSIm) and dipyridyl (bpy or bpe) also produced
      another family of dinuclear rods [Cp*Rh(ImH)3]2.L (6a: L = bpy; 6b: L = bpe).
      Treating 1 and 2 with TMSIm and NH4SCN (in the absence of dipyridyl) generated a
      1-D chain [Cp*Rh(ImH)3](NO3)2 (7) and a 1-D helix [Cp*Rh(eta1-SCN)2(eta1
      SHCN)].H2O (8.H2O), respectively. The structures of complexes 3.CH2Cl2, 4a.H2O,
      4c.2H2O, 5b, 6a, 7 and 8.H2O were determined by X-ray diffraction.

PMID- 15252618
TI  - Total enantioselectivity in the DNA binding of the dinuclear ruthenium(II)
      complex [[Ru(Me2bpy)2]2(mu-bpm)]4+ [bpm = 2,2'-bipyrimidine; Me2bpy = 4,4'
      dimethyl-2,2'-bipyridine].
AB  - The binding of the three stereoisomers (DeltaDelta-, LambdaLambda- and
      DeltaLambda-) of the dinuclear ruthenium(II) complex [[Ru(Me2bpy)2]2(mu-bpm)]4+
      [Me2bpy = 4,4'-dimethyl-2,2'-bipyridine; bpm = 2,2'-bipyrimidine] to a
      tridecanucleotide containing a single adenine bulge has been studied by 1H NMR
      spectroscopy. The addition of the DeltaDelta-isomer to d(CCGAGAATTCCGG)2 induced
      significant chemical shift changes for the base and sugar resonances of the
      residues at the bulge site (G3A4G5/C11C10), whereas small shifts were observed
      upon addition of the enantiomeric LambdaLambda-form. NOESY spectra of the
      tridecanucleotide bound with the DeltaDelta-isomer revealed intermolecular NOE's
      between the metal complex and the nucleotide residues at the bulge site, while
      only weak NOE's were observed to terminal residues to the LambdaLambda-form.
      Competitive binding studies were performed where both enantiomers were
      simultaneously added to the tridecanucleotide, and for all ratios of the two
      stereoisomers the DeltaDelta-isomer remained selectively bound at the bulge site
      with the LambdaLambda-enantiomer localised at the terminal regions of the
      tridecanucleotide. The meso-diastereoisomer (DeltaLambda) was found to bind to
      the tridecanucleotide with characteristics intermediate between the DeltaDelta-
      and LambdaLambda-enantiomers of the rac form. Two distinct sets of metal complex
      resonances were observed, with one set having essentially the same shift as the
      free metal complex, whilst the other set of resonances exhibited significant
      shifts. The NOE data indicated that the meso-diastereoisomer does not bind as
      selectively as the DeltaDelta-isomer, with NOE's observed to a greater number of
      nucleotide residues compared to the DeltaDelta-form. This study provides a rare
      example of total enantioselectivity in the binding of an inert transition metal
      complex to DNA, produced by the shape recognition of both ruthenium(II) centres.

PMID- 15252619
TI  - The dimeric and tetrameric octarepeat fragments of prion protein behave
      differently to its monomeric unit.
AB  - Potentiometric and spectroscopic data have shown that octarepeat dimer and
      tetramer are much more effective ligands for Cu(II) ions than simple octapeptide.
      Thus, the whole N-terminal segment of prion protein due to cooperative effects,
      could be more effective in binding of Cu(II) than simple peptides containing a
      His residue. The gain of the Cu(II) binding by longer octarepeat peptides derives
      from the involvement of up to four imidazoles in the coordination of the first
      Cu(II) ion. This type of binding increases the order of the peptide structure,
      which allows successive metal ions for easier coordination.

PMID- 15252620
TI  - Preparation and topotactical oxidation of ScVO3 with bixbyte structure: a low
      temperature route to stabilize the new defect fluorite ScVO(3.5) metastable
      phase.
AB  - ScVO3 has been prepared by controlled reduction of a ScVO4 precursor under an
      H2/N2 flow at 1250 degrees C. The crystal structure of this material has been
      studied at room temperature by Rietveld refinement of high-resolution neutron
      powder diffraction (NPD) data. Sc3+ and V3+ are distributed at random over the
      metal sites of a C-M2O3 bixbyite-type structure, space group Ia3, a = 9.6182(1)
      Angstroms. The thermal analysis of ScVO3 in an air flow shows two subsequent
      oxidation processes, with a final reversal to ScVO4 above 600 degrees C. An
      intermediate phase of composition ScVO(3.5), containing V4+ cations, can be
      isolated by isothermal annealing at 350 degrees C in air. This metastable phase
      has been identified by X-ray diffraction (XRD) as a fluorite-type oxide (space
      group Fm3m, a = 4.947(2) Angstroms), also showing a random distribution of Sc and
      V cations over the metal positions. The Rietveld refinement of the ScVO(3.5)
      structure from powder XRD data in a fluorite structural model yields abnormally
      high thermal factors for the oxygen atoms, suggesting oxygen mobility in this
      metastable material.

PMID- 15252621
TI  - New mixed alkaline-earth nitridomolybdate(VI) nitride oxides with anion-ordered
      sub-structures.
AB  - New molybdenum(VI) nitride oxides were synthesised by the reaction of strontium
      nitride and calcium nitride with molybdenum foil at high temperature in sealed
      stainless steel crucibles. The reactions yielded single crystalline products
      determined by X-ray diffraction to form complex structures in the triclinic space
      group P1(no. 2). The mixed alkaline earth compounds with composition
      Ca38Sr13[MoN4]12N8O3 and Ca36Sr15[MoN4]12N8O3 are isostructural with the
      quaternary nitride oxides Sr51[WN4]12N8O3 and Ca51[WN4]12N8O3. The structures
      contain isolated [MoN4](6-) tetrahedra, partially disordered alkaline earth
      cations and an ordered sublattice of N(3-) and O(2-) anions. Oxide anions are
      coordinated only to the alkaline earth metals. The title compounds are the first
      mixed alkaline earth metal nitride oxides.

PMID- 15252622
TI  - Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of
      tripodal, hexadentate tris(ethylenediamine)--analogue chelators.
AB  - Three tripodal hexamine chelators based on cis,cis-1,3,5-triaminocyclohexane
      (tach) have been synthesized and their aqueous coordination chemistry with
      Ni(II), Cu(II) and Zn(II) is reported. The chelators have a 2-aminoethyl pendant
      arm attached to each nitrogen of tach, specifically 'tachen'(N,N',N''-tris(2
      aminoethyl)cyclohexane-cis,cis-1,3,5-triamine), and two with S,S,S-chiral pendant
      arms, 'tachpn'(N,N',N''-tris(2-aminopropyl)cyclohexane-cis,cis-1,3,5-triamine)
      and 'tachbn'(N,N',N''-tris(2-amino-3-phenylpropyl)cyclohexane-cis,cis-1,3,5
      triamine. These chelators complex Ni(II), Cu(II) and Zn(II) in aqueous or
      aqueous/methanolic medium. The crystalline products [M(II)L](X)2 are isolated,
      where M = Ni(II), Cu(II) or Zn(II), L = tachen, tachpn or tachbn, and X = ClO4-.
      Crystallographic study of selected tachpn and tachbn complexes shows the chelate
      arms are constrained in a Lambda(deltadeltadelta) configuration about M(II),
      which is attributed to their chirality. Solution UV-vis spectroscopy of the
      Ni(II) and Cu(II) complexes indicates six-coordination and little effect of the
      pendant arm substitution on ligand-field strength. The single exception is
      [Cu(tachbn)]2+, whose spectrum is consistent with five-coordination in solution.
      The cytotoxicities of tachen, tachpn and tachbn toward cultured cancer cells is
      in the order tachen < tachpn < tachbn < tachpyr, where tachpyr is the
      aminopyridyl chelator N,N',N''-tris(2-pyridylmethyl)cyclohexane-cis,cis-1,3,5
      triamine. The cytotoxicity difference is attributed to an order of increasing
      lipophilicity, tachen < tachpn < tachbn.

PMID- 15252624
TI  - A new [2 + 1] mixed ligand concept based on [99(m)Tc(OH2)3(CO)3]+: a basic study.
AB  - Mixed ligand fac-tricarbonyl complexes of the general formula [M(L1)(L2)(CO)3](M
      = Re, 99(m)Tc, L1= imidazole, benzyl isocyanide, L2 = 1H-imidazole-4-carboxylic
      acid, pyridine-2,4-dicarboxylic acid, pyridine-2,5-dicarboxylic acid) have been
      prepared starting from the precursors [M(OH2)3(CO)3]+. The complexes can be
      obtained in good yield and purity in a two-step procedure by first attaching the
      bidentate ligand followed by addition of the monodentate. 99mTc compounds can
      also be prepared at the tracer level in one-pot procedures with L1 and L2 being
      concomitantly present. This [2 + 1] approach allows the labeling of bioactive
      molecules containing a monodentate or a bidentate donor site. Examples given in
      here are N-(tert-butoxycarbonyl)glycyl-N-(3-(imidazol-1
      yl)propyl)phenylalaninamide, 5-((3-(imidazol-1-yl)propyl)aminomethyl)-2'
      deoxyuridine and 4-(5-isonitrilpentyl)-1-(2-methoxyphenyl)-piperazine as L1 and N
      ((6-carboxypyridine-3-yl)methyl)glycylphenylalanine as L2. The corresponding
      second ligand can be used to influence the physico-chemical properties of the
      conjugate. The crystal structures of [99Tc(OH2)(imc)(CO)3], [Re(OH2)(2,4
      dipic)(CO)3], [Re(bic)(2,4-dipic)(CO)3] and [Re(im)(2,5-dipic)(CO)3] are
      reported.

PMID- 15252623
TI  - The coordination chemistry of copper(I) in liquid ammonia, trialkyl and triphenyl
      phosphite, and tri-n-butylphosphine solution.
AB  - The coordination chemistry of the solvate complexes of the relatively soft
      electron-pair acceptor copper(I) has been studied in solution and solid state in
      seven solvents with strong electron-pair donor properties, liquid ammonia,
      trimethyl, triethyl, triisopropyl, tri-n-butyl and triphenyl phosphite, and tri-n
      butylphosphine. The solvate complexes have been characterised by means of EXAFS
      and 63Cu NMR spectroscopy, and in some cases also by 65Cu NMR spectroscopy. The
      copper(I) ion is three-coordinated, most probably in a coplanar trigonal fashion,
      in liquid ammonia with a mean Cu-N bond distance of 2.00(1) Angstroms. No 63Cu
      NMR signal has been detected from the ammonia solvated copper(I) ion in liquid
      ammonia, which supports a three-coordination. The phosphite and phosphine
      solvated copper(I) ions are tetrahedral with Cu-P bond distances in the range
      2.24-2.28 Angstrom in both solution and solid state as determined by EXAFS
      spectroscopy. The tetrahedral configuration of these complexes has been confirmed
      by 63Cu and 65Cu NMR spectroscopy through the J(63Cu-31P) and J(65Cu-31P)
      couplings. The fact that two of the investigated complexes, [Cu(P(OC6H5)3)4]+ and
      [Cu(P(C4H9)3)4]+, are 63Cu and 65Cu NMR silent is probably caused by a
      significantly angular distorted tetrahedral configuration.

PMID- 15252625
TI  - Unexpected formation of a copper(II) 12-metallacrown-4 with (S)-glutamic-gamma
      hydroxamic acid: a thermodynamic and spectroscopic study in aqueous solution.
AB  - The equilibria of copper(II) with (S)-glutamic-gamma-hydroxamic acid (H2L) were
      investigated in aqueous solution by different techniques: glass electrode
      potentiometry; calorimetry; VIS and CD spectrophotometry; and ES-MS. An
      unexpected pentacopper(II) 12-metallacrown-4 [Cu5L4H(-4)](2-) was detected,
      analogous to those well known formed by alpha- and beta-aminohydroxamic acids,
      but of lower stability. Another five species were found: [CuLH]+; [CuL2H2];
      [Cu2L2]; [CuL2H]-; and [CuL2]2-. Their structures are proposed based on both
      spectroscopic and calorimetric data.

PMID- 15252626
TI  - Quantum chemistry-based interpretations on the lowest triplet state of
      luminescent lanthanides complexes. Part 1. Relation between the triplet state
      energy of hydroxamate complexes and their luminescence properties.
AB  - In this paper, we evaluate the potential use of theoretical calculations to
      obtain an energy scale of the lowest ligand-centred triplet excited state in
      luminescent terbium(III) complexes. In these complexes, non-radiative
      deactivation of the terbium emitting state via a back-energy transfer process
      (T1<--Tb(5D4)) is a common quenching process. Consequently the prediction of the
      energy gap between these two excited states should be useful for programming
      highly luminescent Tb(III) systems. We report on a strategy based upon
      experimental and theoretical investigations of the excited state properties of a
      series of four simple aromatic hydroxamate ligands coordinated to Tb(III) and
      Gd(III) ions. By using previously reported crystallographic data, the structural
      and energies properties of these systems were investigated in the ground and
      first excited triplet states at the density functional theory (DFT) level of
      calculations. Our theoretical results are consistent with a triplet excited state
      T1 which is localised on one ligand only and whose the energy level is
      independent of the lanthanide ion nature (Tb(III), Gd(III)). A good agreement
      between the calculated adiabatic transition energies and experimental data
      derived from emission spectra is obtained when a corrective term is considered.
      These satisfactory results are an indication that this type of modelling can lead
      to discriminate in terms of the position of the lowest ligand triplet energy
      level the best antenna among a family of chromophoric compounds. In addition this
      theoretical approach has provided indications that the difference between the
      adiabatic transition energies of all the investigated complexes can be mainly
      explained by metal-ligand electrostatic interactions. The influence of the number
      of antennae on the quantum yield and the luminescence lifetime is discussed.

PMID- 15252627
TI  - Solid-supported cross-coupling catalysts derived from homogeneous nickel and
      palladium coordination complexes.
AB  - Solid-supported catalysts derived from homogeneous nickel(II) and palladium(II)
      non-symmetrical salen-type coordination complexes have been prepared and shown to
      be effective in the heterogeneous catalysis of carbon-carbon cross-coupling
      reactions. The nickel catalyst has been used in room-temperature Tamao-Kumada
      Corriu reactions and the palladium catalyst in the Heck reaction at elevated
      temperatures. The complexes were prepared by improved methods and characterised
      by spectroscopic techniques. Comparisons between the solid-supported catalysts
      and their homogeneous analogues are reported. The single-crystal structure
      determination of the nickel and palladium complexes [M(salenac-OH)][M = Ni, Pd;
      salenac-OH = 9-(2',4'-dihydroxyphenyl)-5,8-diaza-4-methylnona-2,4,8-trienato](2
      )] is reported.

PMID- 15252628
TI  - Mixed nitrogen/oxygen ligand affinities for bipositive metal ions and dioxygen
      binding to cobalt(II) complexes.
AB  - The complex formation of Co(II) and Cd(II) with mixed N/O ligands in
      dimethylsulfoxide (dmso) at 298 K is investigated by means of potentiometric, UV
      Vis, calorimetric, FT-IR, NMR and electrochemical techniques. The linear and
      cyclic ligands investigated are: 2,2'-oxydiethylamine (NON), N-(2-hydroxyethyl)
      ethylenediamine (NNO), 1,4,10-trioxa-7,13-diaza-cyclopentadecane (2,1) and
      1,4,7,10-tetraoxa-13-azacyclopentadecane (2,2). The results are discussed by
      taking into account the donor strength of donor atoms, strain effects in the
      formation of chelate rings, steric and inductive effects and the size of the
      cavity when macrocyclic ligands are concerned. DFT studies are also performed to
      gain an insight into the stabilization of the lower oxidation state of the
      CoL2(2+/3+) couple in order to understand the different reactivity of the Co(II)
      complexes towards dioxygen. The kinetics of dioxygen uptake has been studied by
      UV-Vis measurements and the results reveal an interesting strong solvent effect,
      which is active in lowering the rate constant for formation of the initial
      superoxo complex.

PMID- 15252629
TI  - Cationic Rh complexes with novel spiro tetraarylpentaborate anions prepared from
      arylboronic acids and aryloxorhodium complexes.
AB  - Ar-B(OH)2 (1a: Ar = C6H4OMe-4, 1b: Ar = C6H3Me2-2,6) react immediately with
      Rh(OC6H4Me-4)(PMe3)3 (2) in 5 : 1 molar ratio at room temperature to generate
      [Rh(PMe3)4]+[B5O6Ar4]- (3a: Ar = C6H4OMe-4, 3b: Ar = C6H3Me2-2,6). p-Cresol
      (92%/Rh), anisole (80%/Rh) and H2O (364%/Rh) are formed from 1a and 2. The
      reaction of 1a with 2 for 24 h produces [Rh(PMe3)4]+[B5O6(OH)4]- (4) as a yellow
      solid. This is attributed to hydrolytic dearylation of once formed 3a because the
      direct reaction of 3a with excess H2O forms 4. An equimolar reaction of 2 with
      phenylboroxine (PhBO)3 causes transfer of the 4-methylphenoxo ligand from rhodium
      to boron to produce [Rh(PMe3)4]+[B3O3Ph3(OC6H4Me-4)]- (5). Arylboronic acids 1a
      and 1b react with Rh(OC6H4Me-4)(PR3)3 (6: R = Et, 8: R = Ph) and with Rh(OC6H4Me
      4)(cod)(PR3) (11: R = iPr, 12: R = Ph) to form [Rh(PR3)4]+[B5O6Ar4]- (7a: R = Et,
      Ar = C6H4OMe-4, 7b: R = Et, Ar = C6H3Me2-2,6, 9a: R = Ph, Ar = C6H3Me2-2,6) and
      [Rh(cod)(PR3)(L)]+[B5O6Ar4]- (13b: R = iPr, L = acetone, Ar = C6H3Me2-2,6, 14a: R
      = Ph, L = PPh3, Ar = C6H4OMe-4, 14b: R = Ph, L = PPh3, Ar = C6H3Me2-2,6),
      respectively. Hydrolysis of 14a yields [Rh(cod)(PPh3)2]+[B5O6(OH)4]- (15)
      quantitatively.

PMID- 15252630
TI  - Cation sensors containing a (bpy)Re(CO)3 group linked to an azacrown ether via an
      alkenyl or alkynyl spacer: synthesis, characterisation, and complexation with
      metal cations in solution.
AB  - Two [(bpy)Re(CO)3L]+ complexes (bpy = 2,2'-bipyridine), where L contains an aza
      15-crown-5 ether which is linked to Re via an alkenyl- or alkynyl-pyridine
      spacer, have been synthesised along with model complexes. Solutions of the
      complexes in acetonitrile have been studied by UV-Vis absorption spectroscopy,
      and by 1D and 2D 1H NMR spectroscopy. Strong UV-Vis bands, assigned to
      intraligand charge-transfer transitions localised at the L ligands, blue shift on
      protonation of the azacrown nitrogen atom or on complexation of alkali-metal
      (Li+, Na+ and K+) or alkaline-earth metal (Mg2+, Ca2+ and Ba2+) cations to the
      azacrown; the magnitude of the blue shift is dependent on the cation, with
      protonation giving the largest shift of ca. 100 nm. Cation binding constants in
      the range of log K= 1-4 depend strongly on the identity of the metal cation.
      Protonation or cation complexation causes downfield shifts in the 1H NMR
      resonances from most of the azacrown and L ligand protons, and their magnitudes
      correlate with those of the blue shifts in the UV-Vis bands; shifts in the
      azacrown 1H NMR resonances report on how the different metal cations interact
      with the macrocycle. UV-Vis and 1H NMR spectra of the free L ligands enable the
      effect of the Re centre to be assessed. Together, the data indicate that the
      alkene spacer gives a more responsive sensor than the alkyne spacer by providing
      stronger electronic communication across the L ligand.

PMID- 15252631
TI  - Synthesis and solid state characterisation of mononuclear 2-benzoylpyridine N
      methyl-N-phenylhydrazone palladium(II) complexes.
AB  - 2-Benzoylpyridine N-methyl-N-phenylhydrazone, HL, is a versatile ligand which
      reacts with [Pd(PhCN)2Cl2] forming the coordination compound [HLPdCl2], 1,
      characterized by the presence of the N(py)/N(im) chelate ring. When HL reacts
      with [Pd3(OAc)6] this gives rise to the orthometallated complex [LPd(OAc)],. In
      this case the Pd(II) environment consists of a N(py)/N(im) ring fused to the
      N(im)/C palladacycle and a monodentate acetate anion. Complex undergoes
      methatetical reactions with alkaline halides and complexes of general formula
      [LPdX](3: X = Cl; 4: X = Br; 5: X = I) are obtained. The molecular structures 3-5
      of determined by single-crystal X-ray analysis proved the formation in all cases
      of mononuclear Pd(II) complexes containing a N(py)/N(im)/C terdentate ligand. As
      solid samples only compounds 3-5 exhibited luminescence at room temperature
      (lambdamax approximately 610 nm). This property, quite unusual in Pd(II)
      complexes, is discussed in terms of pi-pi] interactions, which are mainly
      responsible for the existence in the crystalline solid state of dimeric units.

PMID- 15252632
TI  - Peroxomolybdate(VI)-citrate and -malate complex interconversions by pH
      dependence. Synthetic, structural and spectroscopic studies.
AB  - The reaction of potassium molybdate(VI) with biologically relevant ligands,
      citric and malic acids, in the presence of H2O2 was investigated for the effect
      of pH variations on the product pattern. That with citric acid led to the
      formation of the monomeric complex K4[MoO(O2)2(cit)].4H2O (1) in the pH range 7
      9, and dimer K5[MoO(O2)(2-)(Hcit)H(Hcit)(O2)2OMo].6H2O (2) (H4cit = citric acid)
      at pH 3-6 through carboxylate-carboxylic acid hydrogen bonding. The relation with
      the previously identified K4[MoO3(cit)].2H2O (4) and K4[Mo2O5(Hcit)2].4H2O (5)
      were shown. These and other intermediates were shown to react in the pH range 3-6
      to give a more stable species 2; the reaction sequence was demonstrated either by
      the protonation from 1 or the deprotonation of [MoO(O2)2(H2cit)](2-) (8).
      Evidence that 2 exists as a dimer in solution is presented. The reaction with (S)
      malic acid afforded Delta-K(2n)[MoO(O2)2((S)-Hmal)]n.nH2O (3) (H3mal = malic
      acid) that was oxidized further to oxalato molybdate (11) by H2O2. The three
      complexes 1-3 were characterized by elemental analysis, UV, IR and NMR
      spectroscopies, in addition to the X-ray structural studies that show citrate and
      malate being coordinated as bidentate ligands via alpha-alkoxyl and alpha
      carboxylate groups. The formation of these complexes is dictated by pH and their
      thermal stabilities varied with the coordinated hydroxycarboxylate ligands.

PMID- 15252633
TI  - Anionic triazine systems.
AB  - The synthesis of TAS+ C3N3F4- (1) (TAS+ = (Me2N)3S+) and the reactions of 1 with
      Me3SiOSiMe3 and Me3SiCF3 to give TAS+ C3N3F2O- (2) and
      TAS+[(NCF)(NCCF3)(NC(CF3)(2)]- (4) are reported. An isomer of 4,
      TAS+[(NCCF3)2(NCFCF3)]-, compound 6, was obtained by fluoride ion addition to
      (CF3CN)3. From the reactions with Me3SiNMe2 neutral fluoroamino triazines
      C3N3Fn(NMe2)(n-1) (n = 1, 2) were isolated. Possible reaction pathways are
      discussed, the X-ray structures of 1, 2, 4 and 6 were determined.

PMID- 15252634
TI  - Pyrene-sensitised near-IR luminescence from ytterbium and neodymium complexes.
AB  - Ytterbium and neodymium have been shown to exhibit sensitised emission following
      excitation of pyrene chromophores. Sensitised emission is demonstrated in self
      assembled complexes and in azamacrocycle derivatives bearing pendent pyrene
      groups. Energy transfer in these systems is dependent on the nature of the link
      between the ligand and the complex.

PMID- 15252635
TI  - Aminoacid N-substituted 1,4,7-triazacyclononane and 1,4,7,10
      tetraazacyclododecane Zn2+, Cd2+ and Cu2+ complexes. A preparative,
      potentiometric titration and NMR spectroscopic study.
AB  - The pK(a)s and Zn2+, Cd2+ and Cu2+ complexation constants (K) for 1,4,7
      tris[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7-triazacyclononane,
      1, 1,4,7-tris[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7
      triazacyclononane, H(3)2, 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-(1H-3
      indolyl)propionate)]-1,4,7-triazacyclononane, 3, and 1,4,7,10-tetrakis[(2''S)
      acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7,10-tetraazacyclododecane, 4,
      1,4,7,10-tetrakis[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7,10
      tetraazacyclododecane, H(4)5, in 20 : 80 v/v water-methanol solution are
      reported. The pK(a)s within the potentiometric detection range for H(3)1(3+) =
      8.69 and 3.59, for H(6)2(3+) = 9.06, 6.13, 4.93 and 4.52, H(3)3(3+) = 8.79 and
      3.67, H(4)4(4+) = 8.50, 5.62 and 3.77 and for H(8)5(4+) = 9.89, 7.06, 5.53, 5.46,
      4.44 and 4.26 where each tertiary amine nitrogen is protonated. The complexes of
      1: [Zn(1)]2+(9.00), [Cd(1)]2+ (6.49), [Cd(H1)]3+ (4.54) and [Cu(1)]2+ (10.01) are
      characterized by the log(K/dm3 mol(-1)) values shown in parentheses. Analogous
      complexes are formed by 3 and 4: [Zn(3)]2+ (10.19), [Cd(3)]2+ (8.54), [Cu(3)]2+
      (10.77), [Zn(4)]2+ (11.41) [Cd(4)]2+ (9.16), [Cd(H4)]3+ (6.16) and [Cu(4)]2+
      (11.71). The tricarboxylic acid H(3)2 generates a greater variety of complexes as
      exemplified by: [Zn(2)-] (10.68) [Zn(H2)] (6.60) [Zn(H(2)2)+] (5.15), [Cd(2)](-)
      (4.99), [Cd(H2)] (4.64), [Cd(H2(2))]+ (3.99), [Cd(H(3)2)]2+ (3.55), [Cu(2)](-)
      (12.55) [Cu(H2)] (7.66), [Cu(H(2)2)]+ (5.54) and [Cu(2)2](4-) (3.23). The
      complexes of H(4)5 were insufficiently soluble to study in this way. The 1H and
      13C NMR spectra of the ligands are consistent with formation of a predominant
      Zn2+ and Cd2+ Delta or Lambda diastereomer. The preparations of the new pendant
      arm macrocycles H(3)2, 3, 4 and H(4)5 are reported.

PMID- 15252636
TI  - An iron(II) dihydrogen hydrido complex containing the tripodal tetraphosphine
      ligand P(CH2CH2PMe2)3.
AB  - The dihydrogen hydrido complex [FeH(H2)(PP3)]+ 1 (PP3 = P(CH2CH2PMe2)3 2) was
      formed by the protonation of the dihydrido complex FeH2(PP3) 3 with methanol or
      ethanol. The observation of H-D coupling in partially deuterated isotopomers of 1
      and measurement of T1 relaxation times for the hydrido and dihydrogen resonances
      of 1 confirmed the presence of the eta2-dihydrogen ligand. Complex 1 shows
      dynamic NMR behaviour in both the 31P and 1H NMR spectra with facile exchange
      between the protons in the eta2-dihydrogen ligand and the eta1-hydrido ligand.
      The dihydrogen ligand of 1 is easily displaced by both anionic and neutral
      ligands to afford the corresponding hydrido complexes [FeHX(PP3)]+ (X = CO 11, X
      = PPh3 12) or FeHX(PP3)(X = Cl 13, X = Br 14, X = I 15, X = N3 16). Small
      quantities of the alkoxy hydrido complexes FeH(OR)(PP3)(R = Me 4; R = Et 5) are
      observed in methanol and ethanol solutions containing 1. In methanol solution,
      FeH(OMe)(PP3) 4 reacts to form the carbonyl hydrido complex [FeH(CO)(PP3)]+ 11
      and isotopic labelling confirms that the carbonyl ligand of 11 is derived from
      the methanol solvent. The mechanism of methanol oxidation presumably proceeds
      through beta-hydride elimination from FeH(OMe)(PP3) to produce formaldehyde as an
      intermediate which is further dehydrogenated to form the carbonyl ligand.
      [FeH(H2)(PP3)]+ 1 and FeHCl(PP3) 13 react rapidly with paraformaldehyde to also
      form [FeH(CO)(PP3)]+ 11. Complex 11 also decarbonylates acetaldehyde to afford
      the methyl carbonyl complex [FeMe(CO)(PP3)]+ 17. The structure of 17 was
      confirmed by X-ray crystallography.

PMID- 15252637
TI  - Solution dynamics and molecular structure elucidation of novel aluminium
      derivatives containing diaminodimethylsilane ligands.
AB  - The interaction of dimethyldiaminosilane ligands of general formula
      SiMe2(NR2)(NR'2)(NR2, NR'2 = NiHPr, NHtBu, NC4H8, NHCH2CH2NMe2) with AlX3 (X =
      Cl, Me) has been investigated and the synthesis of novel aluminium derivatives is
      reported, namely AlMe3[SiMe2(NR2)(NR'2)], AlX2[SiMe2(NR)(NR'2)] and
      AlMe[SiMe2(NR)2], containing the silane ligand as neutral, monoanionic and
      dianionic species, respectively. Moreover, the solution molecular structures and
      dynamics have been elucidated via 1D/2D variable temperature NMR spectroscopy
      showing the influence of the N-substituents of the silane ligand and of the
      aluminium ancillary ligands.

PMID- 15252638
TI  - In vitro and in vivo stability investigations of Cu(II), Zn(II), Ca(II) and
      Gd(III) complexes with N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine.
AB  - Formation constants of copper(II), zinc(II), calcium(II) and gadolinium(III) with
      N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine (L2) have been studied at
      25 degrees C and an ionic strength of 0.15 mol dm(-3). The reasonably high
      formation constants of the copper with this ligand are due to the ease with which
      the metal ion deprotonates the amide moieties. The square-planar coordination of
      L2 towards copper as predicted from UV-visible data may also account for the high
      selectivity of L2 towards the metal ion. Octanol/water partition coefficients of
      Cu(II)-L2 complexes indicate that although these complexes are largely
      hydrophilic, approximately 1.86% of the [CuL2H(-1)] species goes into the octanol
      layer and hence may promote dermal absorption of copper with a calculated
      penetration rate of 1.24 x 10(-5) cm h(-1). The [CuL2H(-1)] complex which
      predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide
      dismutase. Blood-plasma simulation studies predict that, despite the high
      concentration of zinc and calcium in vivo, L2 is able to increase the low
      molecular-mass fraction of copper. Biodistribution experiments using 64Cu
      labelled [CuL2H(-1)] indicate an initial high uptake of this species in the
      liver, but it is predominantly excreted through the renal system.

PMID- 15252639
TI  - Steric control of lanthanide hydration state: fast water exchange at gadolinium
      in a mono-amide 'DOTA' complex.
AB  - Detailed analyses of the solution structure and exchange dynamics of two sets of
      homologous mono-amide triacetate lanthanide complexes (Ln = Eu, Gd) of cyclen
      have been undertaken. The complex [LnL1], bearing an N-linked CH2CH2NHCO-pyridyl
      moiety, forms mono-aqua (q = 1) species in solution and the Gd complex undergoes
      rapid water exchange (k(ex)= 11 x 10(7) s(-1), 298 K) as a result of the steric
      destabilisation of the Ln-water binding interaction. The homologous complex with
      a C-3 spacing chain, [LnL2], forms a q = 0 species.

PMID- 15252640
TI  - Self-assembled polynuclear clusters derived from some flexible polydentate
      dihydrazide ligands.
AB  - Polynuclear manganese(II), cobalt(II)/(III), iron(II)/(III) and nickel(II)
      complexes of a group of flexible polydentate dihydrazone ligands, based on
      pyridine-2,6-dipicolinic (A), oxalic (B) and malonic (C) subunits are described.
      Structural details are reported for the linear dinuclear complexes
      [Ni2(2poap)2(H2O)2](NO3)4 . 2CH3OH . 2.5H2O (1),
      [Mn2(pttp)(NO3)2(CH3OH)2(H2O)2](NO3)2 . H2O (2) and
      [Mn2(mapttp)2(NO3)2(H2O)2](NO3)2 . 10H2O (3), a square tetranuclear complex
      [Co4(pttp)4]Br6 . 9H2O (4), a tetranuclear tetrahedral complex
      [Ni4(pttp)6](BF4)6F2 . 14H2O (7), and a mixed spin state tetranuclear Ni(II)
      complex [(2pyoap)2Ni4(CH3OH)4] . 1.5CH3OH (10), with a diamond-like arrangement
      of metal ions. The paramagnetic metal centers are well separated in each case,
      leading to weak antiferromagnetic coupling or non-existent spin exchange.

PMID- 15252641
TI  - Electron paramagnetic resonance studies on copper(II)-cyclodextrin systems.
AB  - Three copper(II) complexes containing beta-cyclodextrin (betaCD) derivatives as
      ligands [mono-6-methylamino-6-deoxy-betaCD dithiocarbamate (CDTC), mono-6
      histamino-6-deoxy-betaCD (CDHM) and mono-6-Nalpha-arginyl-6-deoxy-betaCD (CDARG)]
      have been studied by electron paramagnetic resonance. The spectra have been
      recorded at X- and S-bands and different temperatures and simulated to obtain the
      best set of magnetic parameters. In particular, the 300 K spectra are typical of
      the slow motion regime, as expected considering the high molecular weight of the
      ligands. Some structural characteristics of the complexes are proposed on the
      basis of dynamic and covalency parameters obtained from simulation.

PMID- 15252642
TI  - The reduction of tris-dithiolene complexes of molybdenum(VI) and tungsten(VI) by
      hydroxide ion: kinetics and mechanism.
AB  - The kinetic study of the spontaneous reduction of some neutral tris-dithiolene
      complexes [ML3] of molybdenum(VI) and tungsten(VI), (L = S2C6H4(2-), S2C6H3CH3(2
      ) and S2C2(CH3)2(2-); M = Mo or W) by tetrabutylammonium hydroxide in
      tetrahydrofuran-water solutions demonstrates that OH- is an effective reductant.
      Their reduction is fast, clean and quantitative. Depending upon both the molar
      ratio in which the reagents are mixed and the amount of water present, one- or
      two-electron reductions of these tris-dithiolene complexes were observed. If
      Bu4NOH is present in low concentration or/and at high concentrations of water,
      the total transformation of the neutral M(VI) complex into the monoanionic M(V)
      complex is the only observed process. Stopped-flow kinetic data for this reaction
      are consistent with the rate law: -d[ML3]/dt = d[ML3-]/dt = k[ML3][Bu4NOH]. The
      proposed mechanism involves nucleophilic attack of OH- to form a mono-anionic
      seven-coordinate intermediate [ML3OH]-, which interacts with another molecule of
      [ML3] to generate the monoanionic complex [ML3]- transfering the oxygen from
      coordinated OH- to water. Hydrogen peroxide was identified as the reaction
      product. The molybdenum complexes are more difficult to reduce than their
      corresponding tungsten complexes, and the values of k obtained for the molybdenum
      and tungsten series of complexes increase as the ene-1,2-dithiolate ligand
      becomes more electron-withdrawing (S2C6H4(2-) > S2C6H3CH3(2-) > S2C2(CH3)2(2-)).
      This investigation constitutes the only well-established interaction between
      hydroxide ion and a tris(dithiolene) complex, and supports a highly covalent
      bonding interaction between the metal and the hydroxide ion that modulates
      electron transfer reactions within these complexes.

PMID- 15252643
TI  - Cleavage of the peptide bond of beta-alanyl-L-histidine (carnosine) induced by a
      Co(III)-amine complexes: reaction, structure and mechanism.
AB  - Cleavage of the peptide bond occurs when beta]-alanyl-L-histidine (carnosine)
      reacts with [Co(tren)Cl2]+ (tren = tris(2-aminoethyl)amine) to give
      [Co(tren)(histidine)](2+) 1 and [Co(tren)(beta-alanine)](2+) 2.
      [Co(tren)(histidine)](2+) 1 crystallizes in the enantiomorphic space group
      P2(1)2(1)2(1) and 2 crystallizes in the P2(1)/c space group. The mechanism of the
      cleavage reactions were studied in detail for the precursor [Co(tren)Cl2]+ and
      [Co(trien)Cl2]+, which convert into [Co(tren)(OH)2]+/[Co(tren)(OH)(OH2)]2+ and
      [Co(trien)(OH)2]+/[Co(trien)(OH)(OH2)]2+ in water at basic pH (trien = 1,4,7,10
      tetraazadecane). At a slightly basic pH, the initial coordination of the
      substrate (beta-alanyl-L-histidine) is by the carboxylate group for the reaction
      with [Co(tren)Cl2]+. This is followed by a rate-limiting nucleophilic attack of
      the hydroxide group at the beta-alanyl-L-histidine carbonyl group. In a strongly
      basic reaction medium substrate, binding of the metal was through carboxylate and
      amine terminals. On the other hand, for the reaction between [cis-beta
      Co(trien)Cl2]+ and beta-alanyl-L-histidine, the initial coordination of the
      substrate takes place via an imidazole ring nitrogen, independently, and followed
      by a nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine
      carbonyl group. The circular dichroism spectrum for 1 suggests that a very small
      extent of racemization of the amino acid (L-histidine) takes place during the
      cleavage reaction between [Co(tren)Cl2]+ and beta-alanyl-L-histidine. Reaction
      between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine also causes cleavage
      of the peptide bond, producing a free beta-alanyl molecule and a cationic
      fragment [cis-alpha-Co(trien)(histidine)](2+) 3 that crystallizes in the
      optically active space group P2(1)2(1)2(1). Unlike the previous case an
      appreciable degree of racemization of the L-histidine takes place during the
      reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine. Crystals
      containing L-histidine and D-histidine fragments in the [cis-alpha
      Co(trien)(histidine)]2+ moiety were crystallographically documented by mounting a
      number of randomly selected crystals.

PMID- 15252644
TI  - Unique example of flexible phenol coordination in mononuclear manganese
      compounds.
AB  - The synthesis and characterization of six novel mononuclear Mn(II) and Mn(III)
      complexes are presented. The tripodal ligands 2-((bis(pyridin-2
      ylmethyl)amino)methyl)-4-nitrophenol (HL1), 2-[[((6-methylpyridin-2
      yl)methyl)(pyridin-2-ylmethyl)amino]methyl]-4-nitrophenol (HL2), (2
      pyridylmethyl)(6-methyl-2-pyridylmethyl)(2-hydroxybenzyl)amine (HL3) and 2
      ((bis(pyridin-2-ylmethyl)amino)methyl)-4-bromophenol were used. All ligands
      provide an N3O donor set. The compounds [Mn(II)(HL1)Cl2].CH3OH (1),
      [Mn(III)(L1)Cl2] (2), [Mn(II)(HL2)(EtOH)Cl2] (3), [Mn(II)(HL3)Cl2].CH3OH (4),
      [Mn(III)(HL4)Br2] (5) and [Mn(III)(L1)(tcc)] (6), with tcc =
      tetrachlorocatecholate dianion, were synthesized and characterized by various
      techniques such as X-ray crystallography, mass spectrometry, IR and UV-vis
      spectroscopy, cyclic voltammetry, and elemental analysis. Compound 1 crystallizes
      in the triclinic space group P1, compounds 2, 3 and 4 were solved in the
      monoclinic space group P2(1)/c, whereas the structure determination of and
      succeeded in the orthorhombic space groups Pbca and P2(1)2(1)2(1), respectively.
      Notably, the crystal structures of 1 and 3 are the first Mn(II) complexes
      featuring a non-coordinating phenol moiety. Compound 2 oxidizes 3,5-di-tert
      butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high
      substrate concentrations with a turnover number of kcat = 173 h(-1). The
      electronic influence of different substituents in para position of the phenol
      group is lined out.

PMID- 15252645
TI  - Arene-ruthenium complexes with salicyloxazolines: diastereoselective synthesis,
      configurational stability and applications as asymmetric catalysts for Diels
      Alder reactions.
AB  - Reaction of the dimers [RuCl2(eta6-arene)]2 (arene = benzene, p-cymene,
      mesitylene) with salicyloxazolines in the presence of NaOMe gives complexes
      [RuCl(R-saloxaz)(arene)] (1-5) which have been fully characterised. Complexes
      [RuL(iPr-saloxaz)(mes)]Y (L = py, 2-Mepy, 4-Mepy; PPh3; Y- = SbF6 or BPh4) 6-9
      were prepared by treating the chloride 2a with ligand L and NaY (Y- = SbF6 or
      BPh4) in methanol at reflux. Halide complexes [RuX(iPr-saloxaz)(mes)](X = Br, 10;
      X = I, 11) were synthesised by treating 2a with AgSbF6 then with 1.2 equivalents
      of KBr or NaI, the methyl complex [RuMe(iPr-saloxaz)(mes)] 12 was synthesised
      from 2a by reaction with MeLi. Five complexes, [RuCl(iPr-saloxaz)(mes)] 2a,
      [RuCl(tBu-saloxaz)(p-cymene)] 3b, [RuCl(Ph-saloxaz)(mes)] 5a, [Ru(4-Mepy)(iPr
      saloxaz)(mes)][SbF6] 7, and [Ru(PPh3)(iPr-saloxaz)(mes)][SbF6] 9, have been
      characterised by X-ray crystallography. Treatment of complexes 1-5 with AgSbF6
      gives cationic species which are enantioselective catalysts for the Diels-Alder
      reaction of acroleins with cyclopentadiene, the effect of substituents on
      enantioselectivity has been examined.

PMID- 15252646
TI  - Reversible and selective amine interactions of [Cd(mu2-N,O-p
      NH2C6H4SO3)2(H2O)2]n.
AB  - [Cd(mu2-N,O-p-NH2C6H4SO3)2(H2O)2]n (1) is a layered coordination compound. The
      solid-vapor reactions between crystalline 1 and a series of volatile amines were
      investigated and the corresponding amine adducts were characterized by EA, TGA,
      PXRD and IR. Among them, the C2H5NH2 and C3H7NH2 adducts, namely
      [Cd(C2H5NH2)4(H2O)2](H2NC6H4SO3)2 (3) and [Cd(C3H7NH2)4(O-p-H2NC6H4SO3)2].C3H7NH2
      (4), grew into single crystals in situ from the solid-vapor reaction processes
      and their crystal structures were characterized. In both cases, 4 mol equiv. of
      amine molecules coordinate to Cd(II) via replacing the N,O-p-NH2C6H4SO3 ligands
      or coordinated water molecules. The single-phase product suggests that the solid
      vapor reaction between the metal sulfonate and volatile alkylamines could be used
      as a green process to synthesize monoamine-coordinated Cd(II) complexes without
      any solvent and routine separation. Finally, the substitution reaction is
      reversible at room conditions and selective for primary alkylamines.

PMID- 15252647
TI  - Poly(guanidyl)silanes as a new class of chelating, N-based ligand.
AB  - The series of poly(guanidyl)silanes RnSi[hpp](4-n) [hpp = 1,3,4,6,7,8-hexahydro
      2Hpyrimido[1,2-a]pyrimidinate; R = Me, n= 1, 2; R = Ph, n= 1] have been
      synthesised and their coordination behaviour at copper(I) halides investigated.

PMID- 15252648
TI  - A novel dinuclear cyclometalated iridium complex bridged with 1,4-bis[pyridine-2
      yl]benzene: its structure and photophysical properties.
AB  - The synthesis, structure, and photophysical properties of a new cyclometalated
      dinuclear iridium complex, (ppy)2Ir(mu-BPB)Ir(ppy)2 [ppy = 2-phenylpyridine, BPB
      = 1,4-bis(pyridin-2-yl)benzene], have been investigated.

PMID- 15252649
TI  - PtCl(PHCy2)[(PCy2O)2H]: a hydrogen bonded phosphinito complex obtained by direct
      reaction of molecular oxygen with a terminal phosphido complex.
AB  - Exposure of solid trans-[Pt(PHCy2)2(PCy2)Cl] (1) to dry oxygen unexpectedly leads
      to [PtCl(PHCy2)[(PCy2O)2H]] (2) as the major product, the formation of which has
      been followed by NOESY 1H NMR techniques.

PMID- 15252650
TI  - Liquid crystals of silver complexes derived from simple 1-alkylimidazoles.
AB  - A homologous series of silver complexes of 1-alkylimidazoles (R-im, R =
      CnH(2n+1), where n= 10, 12, 14, 16 and 18) was synthesized. All the CnH(2n+1)-im
      ligands are non-mesomorphic. Upon complexation, all the [Ag(CnH(2n+1)-im)2]
      [NO3], except for n = 10, exhibit liquid crystalline properties. The crystal
      structure of [Ag(C12H25-im)2][NO3] shows that the silver center is two-coordinate
      and adopts a U-shaped conformation with bilayer packing. The non-mesomorphic
      [Ag(C16H33-bim)2][NO3](bim = benzimidazole) has a three-coordinate silver ion and
      has a chair conformation with monolayer stacking. Non-mesomorphic [Ag(C16H33
      bim)2][BF4] has a linear geometry around the silver ion and also has a chair
      conformation. The mesophase for the Ag-(CnH(2n+1)-im) complexes has been
      identified as the smectic A (SmA) phase. [Ag(C16H33-im)2]+ with four different
      anions, NO3-, BF4-, PF6- and CF3SO3- were compared. Of the four Ag-im complexes,
      only that with the CF3SO3- anion does not show liquid-crystal behavior.

PMID- 15252651
TI  - Transition metal-directed self-assembly of calix[4]arene based dithiocarbamate
      ligands.
AB  - The transition metal-directed self-assembly of dithiocarbamate ligand
      functionalized upper and lower rim calix[4]arenes affords novel dimeric
      bimetallic bis(calix[4]arene) species as determined by a combination of
      analytical methods including X-ray crystallography. An exception is a zinc(II)
      dithiocarbamate upper rim calix[4]arene assembly which is monomeric in nature.
      Electrochemical investigations reveal the bimetallic copper(II)
      bis(calix[4]arene) systems can electrochemically sense dihydrogen phosphate and
      carboxylate anions via significant cathodic perturbations of the respective
      copper(II)/(III) dithiocarbamate oxidation wave.

PMID- 15252652
TI  - Structural and near-IR photophysical studies on ternary lanthanide complexes
      containing poly(pyrazolyl)borate and 1,3-diketonate ligands.
AB  - The ligands tris[3-(2-pyridyl)pyrazol-1-yl]hydroborate (L1, potentially
      hexadentate) and bis[3-(2-pyridyl)pyrazol-1-yl]dihydroborate (L2, potentially
      tetradentate) have been used to prepare ternary lanthanide complexes in which the
      remaining ligands are dibenzoylmethane anions (dbm). [Eu(L1)(dbm)2] is eight
      coordinate, with L1 acting only as a tetradentate chelate (with one potentially
      bidentate arm pendant) and two bidentate dbm ligands. [Nd(L1)(dbm)2] was also
      prepared but on recrystallization some of it rearranged to [Nd(L1)2][Nd(dbm)4],
      which contains a twelve-coordinate [Nd(L1)2]+ cation (two interleaved hexadentate
      podand ligands) and the eight-coordinate anion [Nd(dbm)4]- which, uniquely
      amongst eight-coordinate complexes having four diketonate ligands, has a square
      prismatic structure with near-perfect O8 cubic coordination. Formation of this
      sterically unfavourable geometry is assumed to arise from favourable packing with
      the pseudo-spherical cation. The isostructural series of complexes
      [Ln(L2)(dbm)2](Ln = Pr, Nd, Eu, Gd, Tb, Er, Yb) was also prepared and all members
      structurally characterised; again the metal ions are eight-coordinate, from one
      tetradentate ligand L2 and two bidentate dbm ligands. Photophysical studies on
      the complexes with Ln = Pr, Nd, Er, and Yb were carried out; all show the near-IR
      luminescence characteristic of these metal ions, with longer lifetimes in CD3OD
      than in CH3OH. For [Yb(L2)(dbm)2], two species with different luminescence
      lifetimes were observed in CH3OH solution, corresponding to species with zero or
      one coordinated solvent molecules, in slow exchange on the luminescence
      timescale. For [Nd(L2)(dbm)2] a single average solvation number of 0.7 was
      observed in MeOH. For [Pr(L2)(dbm)2] a range of emission lines in the visible and
      NIR regions was detected; time-resolved measurements show a particularly high
      susceptibility to quenching by solvent CH and OH oscillators.

PMID- 15252653
TI  - DNA binding and biological activity of some platinum(II) intercalating compounds
      containing methyl-substituted 1,10-phenanthrolines.
AB  - This study documents the first detailed investigation into the relationship
      between molecular structure and biological activity of platinum(II) complexes
      containing methylated derivatives of 1,10-phenanthroline (phen). A series of
      square planar platinum(II) compounds incorporating methylated derivatives of
      phen, 4-methyl-1,10-phenanthroline (4-Mephen), 5-methyl-1,10-phenanthroline (5
      Mephen), 4,7-dimethyl-1,10-phenanthroline (4,7-Me2phen), 5,6-dimethyl-1,10
      phenanthroline (5,6-Me2phen) and 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8
      Me4phen) were synthesised and the relationship between their structure and
      biological activity investigated. The biological activity of these compounds was
      quantified using the in vitro cytotoxicity assay against the L1210 Murine
      leukaemia cell line. Large variation in cytotoxicities with different methylation
      was observed. The 5- and 5,6-methylated derivatives of phen displayed a greater
      biological activity, with IC50 values of 2.8 +/- 0.8 microM and 1.5 +/- 0.3
      microM respectively, compared with the phen compound, with an IC50 value of 9.7
      +/- 0.3 microM, while all the others were inactive with IC50 values over 50
      microM. Binding constants were determined using circular dichroism spectroscopy
      (CD) and induced circular dichroism (ICD). ICD was used to highlight any
      differences in the spectra. Viscometry studies and linear dichroism (LD)
      experiments indicate that the platinum(II) complexes intercalate although for
      [Pt(en)(4-Mephen)]Cl2 and [Pt(en)(4,7-Me2phen)]Cl2 this mode of binding appears
      to be concentration dependent. The binding of the platinum(II) complexes to the
      oligonucleotide d(GTCGAC)2 was studied using two-dimensional 1H NMR spectroscopy.
      The addition of each metal complex to the hexamer d(GTCGAC)2 produced upfield
      shifts of the metal complex resonances, characteristic of intercalation. Through
      the observation of NOE cross-peaks, two-dimensional NMR studies provided insight
      into the site and groove preferences of these compounds when binding to DNA.

PMID- 15252654
TI  - Fused pyridazines: rigid multidentates for designing and fine-tuning the
      structure of hybrid organic/inorganic frameworks.
AB  - Fused pyridazines (1,2,3,6,7,8-hexahydro-cinnolino[5,4,3-cde]cinnoline, L and its
      2,2,7,7-tetramethyl derivative, Me4L) are designed as rigid multidentate ligands
      for the construction of framework solids. In combination with copper(I) bromide
      (iodide) they provide excellent structural examples for predictive engineering
      and the possibilities for further fine-tuning of the framework architectures
      facilitated by the tetradentate function of the ligands and effective cooperation
      of organic and inorganic bridges. This study features control over helical
      structures for (CuX)n chains and homo/heterochiral combination of the helices in
      the lattice, the design of a range of channelled and tubular CuX networks and the
      structural significance of ligand shape complementarity. 3D tetragonal Cu2X2(L)
      frameworks exist either as chiral or achiral supramolecular isomers Cu2I2(Me4L)
      and Cu12I12[Cu(CH3CN)]3(L)(6-)Cu3I6.CH3CN illustrate 3D hexagonal channelled and
      tubular arrays; Cu2I2(Me4L)(CH3CN) and Cu4I4(L)(CH3CN)2 complexes are 1D
      polymers.

PMID- 15252655
TI  - Modulation of the metal recognition properties of a new type of azaferrocenophane
      based chemosensors: co-ordination chemistry towards Mg2+, Ca2+, Zn2+ and Ni2+.
AB  - The structure-redox chemistry relationship of a new type of azaferrocenophane
      based chemosensors, 3 and 4, in the presence of protons and several kinds of
      metal ions, has been studied. Electrochemical studies, carried out in CH2Cl2, in
      the presence of increasing amounts of Mg2+, Ca2+, Zn2+ and Ni2+ showed that the
      wave corresponding to the Fc/Fc+ couple of the uncomplexed ligands is gradually
      replaced by a new reversible wave at more positive potentials corresponding to
      the Fc/Fc+ couple of the complexed ligands. The maximum shift of the ferrocene
      oxidation wave was found for 4b in the presence of Mg2+, whereas for 3f a
      selective sensing response for Mg2+ in the presence of hydrated Ca2+ cations was
      observed, with a concomitant highly visual output response consisting of a deep
      purple colour.

PMID- 15252656
TI  - Synthesis, characterization and DFT studies of the cobalt(III) complex of a
      tetrapodal pentadentate N4S donor ligand.
AB  - The synthesis of the pentadentate ligand 2,6-bis(3,3-dimethyl-2,4
      dioxocyclohexanyl)-4-thiaheptane (N4Samp) is described. The synthetic pathway
      involves the coupling of two 1,3-(dimethylenedioxy)-2-methyl-2-(methylene-p
      toluenesulfonyl)propane moieties with sodium sulfide and subsequent synthetic
      elaboration to prepare the final N4S donor system. The cobalt(III) complex
      [Co(N4Samp)Cl]2+ has been prepared and subsequently crystallized as the
      tetrachlorozincate salt. The X-ray structure analysis confirms the pentadentate
      nature of the ligand and shows the thioether donor occupying one apex with four
      equivalent amine donors effectively occupying the equatorial plane of the
      molecule. The sixth coordination site is occupied by a chloro ligand. The
      electronic absorption and 13C NMR spectra have been studied. DFT calculations
      have been employed to explore structural and mechanistic comparisons between
      [Co(N4Samp)Cl]2+ and an analogous pentaaamine complex.

PMID- 15252657
TI  - Anionic Fischer-type carbene complexes as bidentate (N,O) ligands.
AB  - New polynuclear complexes, (L1)3M2 [M2 = Cr(III) (4a,4b), Fe(III) (5), Co(III)
      (8)], (L1)2M2(L2)2 [M2 = Co(II) (7), Ni(II) (9)], (L1)2M2(O)L2 [M2 = V(IV) (6)]
      and L1M2Cp2 [M2 = Ti(III) (10)] with L1 = (CO)5M1=C[C=NC(CH3)=CHS](O-)(M1 = Cr or
      W) and L2 = 4-methylthiazole or THF, are described. The molecular structures of
      these complexes determined by X-ray diffraction show that the Fischer-type
      carbene complexes act as bidentate ligands towards the second metal centre,
      coordinating through C(carbene)-attached O-atoms and imine N-atoms of the
      thiazolyl groups to form five-membered chelates with the oxygen atoms in the mer
      configuration. Isostructural complexes have similar characteristic band patterns
      in their far-IR spectra. Cyclic voltammetry of selected complexes reveals the
      oxidation of the carbene complex ligand between 1.01 and 1.29 V. Oxidation of the
      central metal (M2) takes place at 0.56 and 0.86 V for 7 and 9, respectively.
      Three stepwise reductions of Cr(III) to Cr(0) occur for 4a and 4b in the region 
      0.51 to -1.58 V. These new ligand types and other variants thereof should find
      application in ligand design with the first metal -- and other ligands attached
      thereto -- in the carbene complex ligand, playing an important role.

PMID- 15252658
TI  - Synthesis and characterisation of cyclopentadienyl complexes of barium:
      precursors for atomic layer deposition of BaTiO3.
AB  - Cyclopentadienyl complexes Ba(C5Me5)2(THF)2 (1), Ba(C5Me5)2(A) (A = THF, dien,
      trien, diglyme, triglyme) (2-5), Ba(Pr(i)3C5H2)2(THF)2 (6), Ba(Bu(t)3C5H2)2(THF)
      (7), Ba(Me2NC2H4C5Me4)2 (8) and Ba(EtOC2H4C5Me4)2 (9) were prepared and
      characterised with TGA/SDTA, NMR and MS. Crystal structures of 2, 4, 5, 7, 8 and
      9 are presented. All complexes prepared sublime under reduced pressure and
      complexes 1, 6 and 7 showed volatility also under atmospheric pressure. Complexes
      1, 6 and 7 lose the coordinated THF when evaporated while complexes 2-5 are
      sublimable as complete molecules under reduced pressure. Complexes with bulky
      cyclopentadienyl ligands (6 and 7) are the most thermally stable and volatile
      among the prepared barocenes. X-ray structure determinations reveal that all the
      complexes studied are monomeric. Complexes 1, 7 and 8 were successfully tested in
      BaTiO3 thin film depositions by atomic layer deposition (ALD).

PMID- 15252659
TI  - Recognition of phosphate monoester dianion by an alkoxide-bridged dinuclear
      zinc(II) complex.
AB  - Recognition of phosphate monoester dianion by an alkoxide-bridged dinuclear
      zinc(II) complex (Zn2L3+) has been studied (L = alkoxide species of 1,3
      bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol). Potentiometric pH titration study
      disclosed a 1 : 1 phenyl phosphate complexation with Zn2L3+ in aqueous solution.
      The dissociation constant (= [Zn2L3+][PhOPO3(2-)]/[Zn2L3+-PhOPO3(2-)]) is an
      extremely small value of 2.5 x 10(-8) mol dm(-3) at 25 degrees C with I = 0.10
      (NaNO3). The X-ray crystal analysis of the dizinc(II) complex with p-nitrophenyl
      phosphate showed that the phosphate dianion binds as a bridging ligand to the two
      zinc(II) ions.

PMID- 15252660
TI  - Hetero di- and trinuclear Cu-Gd complexes with trifluoroacetate bridges:
      synthesis, structural and magnetic studies.
AB  - The synthesis, structural determinations and magnetic properties of an original
      dinuclear Cu-Gd and two trinuclear Cu-Ln-Cu complexes (Ln = Gd or Dy) made with a
      Schiff base ligand and carboxylate ligands are reported. In each complex, the
      copper and gadolinium or dysprosium ions are linked by a double phenoxo bridge
      and a eta1:eta1:mu trifluoroacetato bridge. The dinuclear Cu-Gd complex exhibits
      the usual ferromagnetic interaction while the trinuclear (Cu-Gd-Cu) complexes can
      not be fitted with a simple Hamiltonian that only takes into account the Cu-Gd
      interaction. Introduction into the Hamiltonian of a Cu-Cu interaction between the
      terminal copper ions gives a nice fit in the case of a ferromagnetic Cu-Cu
      interaction (J'(Cu-Cu) = 8.3 and 9.8 cm(-1)). For the first time, the occurrence
      of a ferromagnetic interaction between the copper ions of the trinuclear entities
      is evidenced and supported by the field dependence of the magnetization. As there
      is no direct proof for the existence of an interaction between two centers
      through a third magnetic center located in between them, we can conclude that the
      existence of pi-pi stacking interactions through the phenyl rings of the ligands
      are responsible for the presence of these interactions.

PMID- 15252661
TI  - Synthesis, structure and comparison of the DNA cleavage ability of metal
      complexes M(II)L with the N-(2-ethoxyethanol)-bis(2-picolyl)amine ligand L (M =
      Co, Ni, Cu and Zn).
AB  - Complexes of a N,N-bis(2-picolyl)amine (bpa) derivative with a pendant
      ethoxyethanol side chain (bpa(CH2)2O(CH2)2OH) (1) with late divalent transition
      metal ions Co(II), Ni(II), Cu(II) and Zn(II) have been studied. All complexes,
      [[bpa(CH2)2O(CH2)2OH]Co(NO3)](NO3) (1Co), [[bpa(CH2)2O(CH2)2OH]Ni(NO3)](NO3)
      (1Ni), [[bpa(CH2)2O(CH2)2OH]Cu(H2O)(NO3)](NO3) (1Cu) and
      [[bpa(CH2)2O(CH2)2OH]Zn(NO3)](NO3) (1Zn), were comprehensively characterized and
      their X-ray single crystal structures have been determined. The complexes show
      hexacoordinated geometries, in which 1 acts as a tetradentate (1Cu) or
      pentadentate (1Co, 1Ni and 1Zn) ligand. DNA cleavage experiments have been
      performed on supercoiled double stranded DNA plasmids in order to compare the
      cleavage efficiency of all four metals in the same ligand environment of 1. In
      this assay, 1Co and 1Cu showed the highest cleavage efficiency, whereas 1Ni and
      1Zn were virtually inactive. Quantification of the gel electrophoresis bands
      showed that more than 80% of the plasmid has suffered at least one single strand
      cut in the case of 1Cu, and about 50% of the plasmid was nicked by 1Co. The
      differential cleavage activity is discussed in relation to the structural
      findings and a mechanism is proposed for 1Cu.

PMID- 15252662
TI  - Metallocorroles as sensing components for gas sensors: remarkable affinity and
      selectivity of cobalt(III) corroles for CO vs. O2 and N2.
AB  - Most commercially available CO detectors are based upon metal oxides or
      electrochemical cell technologies. None of these approaches use the selective
      adsorption of CO gas on a molecular complex. Conversely, cobalt(III) corroles can
      bind small gaseous molecules allowing them for an application as sensing
      components for gas detectors. Here we describe the ability of cobalt corroles to
      selectively coordinate carbon monoxide vs. dinitrogen and dioxygen. The
      coordination properties were determined in the solid state and the adsorption
      characteristics were compared to those of the reference compound (To-PivPP)Fe(1,2
      Me2Im), known for its remarkable CO binding properties. The adsorption data
      evidence that the selectivity, affinity and capacity of the cobalt(III) corroles
      for CO are larger than those of the porphyrin complex. However, from a chemical
      point of view, the selectivity of cobalt(III) corroles for CO vs. O2 is infinite
      since these derivatives do not bind O2 while (To-PivPP)Fe(1,2-Me2Im) does with an
      M value (PO2(1/2)/PCO(1/2)) equal to 51. In this manuscript we also show that the
      affinity of cobalt(III) corroles for CO is closely related to the Lewis acid
      character of the central cobalt(III) ion and therefore to the nature of the
      substituents at the periphery of the corrole macroring.

PMID- 15252663
TI  - Strain-induced substitutional lability in a Ru(II) complex of a hypodentate
      polypyridine ligand.
AB  - The ruthenium(II) complex of heptadentate N,N,N',N'-tetrakis(2-pyridylmethyl)-2,6
      bis(aminomethyl)pyridine (tpap) was isolated as the hexafluorophosphate complex
      Ru(tpap)(PF6)2. The crystal structure has been determined for the triflate salt
      Ru(tpap)(CF3SO3)2.2H2O, which crystallizes in the monoclinic space group P2(1)/n.
      The structure was refined to a final R value of 0.0549 for 5894 observed
      reflections. The heptadentate ligand coordinates with six nitrogens, i.e. with
      two tertiary nitrogens and four pyridine nitrogens, one of the pyridines
      remaining un-coordinated. The resulting structure is significantly distorted from
      octahedral geometry with an equatorial Nsp3-Ru-Npyridine angle of 120 degrees.
      The consequence of the above steric strain is a labilization of the system and
      fluxional behaviour involving exchange between equatorially coordinated and non
      coordinated pyridines has been observed by 1H NMR for Ru(tpap)(PF6)2 in d6
      acetone solution. The activation parameters of DeltaG(not equal to 298) = 53 kJ
      mol(-1), DeltaH(not equal) = 56 +/- 1 kJ mol(-1) and DeltaS(not equal) = -10 +/-
      3 J mol(-1) K(-1) were determined on the basis of NMR experiments. In addition
      electronic structure calculations applying density functional theory (DFT) have
      been performed in order to identify a transition state and to estimate the
      activation barrier. On the basis of NMR and DFT results the mechanism of
      isoexchange involving a hepta-coordinated intermediate has been proposed.

PMID- 15252664
TI  - Syntheses and structural systematics of trialkylphosphine complexes of open
      titanocenes, zirconocenes and hafnocenes.
AB  - The synthesis and characterization of the open hafnocene, Hf(2,4
      C7H11)2(PMe3)(C7H11 = dimethylpentadienyl), is reported. Additionally, a much
      improved synthetic procedure has been developed for Hf(2,4-C7H11)2(PEt3).
      Structural data have been obtained for these complexes, and for Ti(2,4
      C7H11)2(PEt3) and Zr(2,4-C7H11)2(PMe3), thereby allowing for detailed comparisons
      between all M(2,4-C7H11)2(PX3) species (M = Ti, Zr, Hf; X = Me, Et). The presence
      of the coordinated phosphines led in all cases to the adoption of the expected
      syn-eclipsed geometries, with the phosphines positioned by the open dienyl edges.
      These phosphine ligands lead to substantial alterations of the bonding patterns
      in these species, relative to ligand-free complexes. Most notably, the shortest M
      C distances involve the central dienyl carbon atoms. Additionally, the data
      reveal high degrees of steric crowding within these complexes, especially for the
      weakly bound Ti(2,4-C7H11)2(PEt3), and also demonstrate that significant
      deformations which have taken place within the dienyl ligands were substantially
      determined by the relative sizes of the metal centers.

PMID- 15252665
TI  - Photophysical properties of closely-coupled, binuclear ruthenium(II)
      bis(2,2':6',2''-terpyridine) complexes.
AB  - The photophysical properties of closely-coupled, binuclear complexes formed by
      connecting two ruthenium(II) bis(2,2':6',2''-terpyridine) complexes via an
      alkynylene group are compared to those of the parent complex. The dimers exhibit
      red-shifted emission maxima and prolonged triplet lifetimes in deoxygenated
      solution. Triplet quantum yields are much less than unity and the dimers generate
      singlet molecular oxygen with low quantum efficiency. Temperature dependence
      emission studies indicate coupling to higher-energy triplet states while cyclic
      voltammetry shows that the metal centres are only very weakly coupled but that
      extensive electron delocalization occurs upon one-electron reduction. The
      radiative rate constants derived for these dimers are relatively low, because the
      lowest-energy metal-to-ligand, charge-transfer states possess increased triplet
      character. In contrast, the rate constants for nonradiative decay of the lowest
      energy triplet states are kept low by extended electron delocalization over the
      polytopic ligand. The poor triplet yields are a consequence of partitioning at
      the second triplet level.

PMID- 15252666
TI  - Effect of the parent ligand on the photophysical properties of closely-coupled,
      binuclear ruthenium(II) tris(2,2'-bipyridine) complexes.
AB  - The photophysical properties of closely-coupled, binuclear complexes formed by
      connecting two ruthenium(II) tris(2,2'-bipyridine) complexes via an alkynylene
      group differ significantly from those of the relevant mononuclear complex. In
      particular, the energy of the first triplet excited state is lowered relative to
      the parent complex, because of the presence of the alkynylene substituent, while
      the triplet lifetime is prolonged, in part, because of extended electron
      delocalization. We now report that the triplet lifetime is also affected by the
      nature of the spectator 2,2'-bipyridyl ligands. Thus, replacing the parent 2,2'
      bipyridine ligands with the corresponding 4,4'-dinitro-substituted ligands serves
      to decrease the luminescence yield and lifetime. With the corresponding
      carboxylate ester, the luminescence yield and lifetime are increased.
      Perdeuteration of the parent 2,2'-bipyridine ligands also leads to a modest
      increase in the luminescence yield. Such observations are indicative of
      electronic coupling between the various metal-to-ligand, charge-transfer excited
      triplet states. Temperature dependence studies confirm that these excited states
      are closely spaced and thermally accessible at ambient temperature. For some of
      the binuclear complexes, the quantum yield for formation of the lowest-energy
      triplet state is significantly less than unity.

PMID- 15252667
TI  - Reactions of lanthanoid metals with 3,5-diphenylpyrazole at elevated
      temperatures: synthesis and structures of both homoleptic, [Ln3(Ph2pz)9] (Ln =
      La, Nd), [Ln2(Ph2pz)6] (Ln = Er, Lu), and heteroleptic, [Ln(Ph2pz)3(Ph2pzH)2] (Ln
      = La, Nd, Gd, Tb, Er or Yb), pyrazolate complexes.
AB  - The direct reaction of lanthanoid metals with 3,5-diphenylpyrazole (Ph2pzH) at
      300 degrees C under vacuum in the presence of mercury gives the structurally
      characterized [Ln3(Ph2pz)9] (Ln = La or Nd), [Ln2(Ph2pz)6] (Ln = Er or Lu).
      Similar reactions provided heteroleptic [Ln(Ph2pz)3(Ph2pzH)2] (Ln = La, Nd, Gd,
      Tb, Er and Y). The last was obtained only from impure Ph2pzH, but was
      subsequently prepared by treatment of [Yb(Ph2pz)3(thf)2] with Ph2pzH. Reactions
      of Yb with Ph2pzH at 200 degrees C gave a poorly soluble divalent species which
      was converted by 1,2-dimethoxyethane into [Yb(Ph2pz)2(dme)2]. Single crystal X
      ray structures established a bowed trinuclear pyrazolate-bridged structure for
      [Ln3(Ph2pz)9] (Ln = La or Nd), Ln...Ln...Ln being 135.94(1) degrees (La) and
      137.41(1) degrees(Nd). There are two eta2-Ph2pz ligands on the terminal Ln atoms
      and one on the central metal with adjacent Ln atoms linked by one mu-eta2:eta2
      and one mu-eta5 (to terminal Ln):eta2 pyrazolate group. Thus the terminal Ln
      atoms are formally nine-coordinate and the central Ln, ten-coordinate. By
      contrast, [Ln2(Ph2pz)6] (Ln = Er or Lu) complexes are dimeric with two terminal
      (eta2) and two bridging (mu-eta2:eta2) pyrazolates and eight-coordinate
      lanthanoids. All six heteroleptic complexes [Ln(Ph2pz)3(Ph2pzH)2] (Ln = La, Nd,
      Gd, Tb, Er or Yb) are isomorphous with three equatorial eta2-Ph2pz groups,
      transoid(N-Ln-N 158.18(6)-161.43(9) degrees) eta1-pyrazole ligands, and eight
      coordinate Ln throughout.

PMID- 15252668
TI  - Interaction of desferrioxamine B (DFB) model dihydroxamic acids with some
      essential and toxic metal(II) ions: effects of the structure and length of
      connecting chains on the metal ion selectivity.
AB  - Complexation of desferrioxamine B (DFB) model dihydroxamic acids
      (HO(CH3)NCO(CH2)xCONH(CH2)yCON(CH3)OH where x = 2, 3, y = 5, 4, 3, 2, and the
      compounds are abbreviated as 2,5-DIHA, 2,4-DIHA, 2,3-DIHA, 2,2-DIHA, 3,4-DIHA and
      3,3-DIHA, respectively) with Cu(II), Ni(II), Zn(II), Pb(II) and Cd(II) was
      studied by pH-potentiometric and spectroscopic (UV-VIS, NMR and ESI-MS)
      techniques. The effects of the position of the peptide group, the chain length
      and the geometry on the stability and stoichiometry of the complexes formed were
      evaluated. It was concluded that metal ions preferring regular octahedral
      geometry in their complexes form the most stable bis-chelated mononuclear
      complexes, [ML], with 2,5-DIHA having the same connecting chain structure and
      length as those of DFB. This benefit of 2,5-DIHA, however, almost disappears in
      the case of Cu(II). With this metal, which prefers the equatorial coordination of
      two hydroxamates, the parallel formation of both [CuL] and [Cu2L2] was found. ESI
      MS results indicate that the latter complex is exclusively formed with 2,2-DIHA
      involving the shortest linker. All these dihydroxamic acids are excellent
      chelating agents for Pb(II). The special geometry determined by the lone pair
      electrons should be responsible for the somewhat unique preference order of the
      ligands towards the Pb(II) ion, for the favoured formation of the monomeric bis
      chelated complexes and also for the unexpectedly high stability of the species
      [Pb(2,2-DIHA)].

PMID- 15252669
TI  - Reactivity of the dimesityl-1,8-naphthalenediylborate anion: isolation of the
      borataalkene isomer and synthesis of 1,8-diborylnaphthalenes.
AB  - The anionic boron peri-bridged naphthalene derivative, namely dimesityl-1,8
      naphthalenediylborate (1), undergoes a hydrolysis reaction to afford dimesityl-1
      naphthylborane (2) whose structure has been determined. Upon standing at room
      temperature in toluene for an extended period of time, 1 undergoes a ring
      expansion reaction to afford 8,10,11a-trimethyl-7-mesityl-11aH-7
      boratabenzo[de]anthracene (3). As shown by its crystal structure, compound 3
      constitutes a rare example of a borataalkene and features a carbon-boron double
      bond of 1.475(6) Angstroms incorporated in a conjugated hexa-1-boratatriene
      system. The reaction of 1 with 9-chloro-9-borafluorene and 5-bromo-10,11
      dihydrodibenzo[b,f]borepin results in the formation of diboranes 4 and 5 which
      bear two different boryl moieties at the peri-positions of naphthalene. These
      diboranes have been characterized by multinuclear NMR spectroscopy and X-ray
      single crystal analysis. The boron center of the borafluorenyl moiety is pi
      coordinated to the ipso-carbon of a mesityl group with which it forms a contact
      of 2.730(3) Angstroms. The cyclic voltammogram of 2 in THF shows a quasi
      reversible reduction wave at E(1/2)-2.41 V (vs. Fc/Fc+) corresponding to the
      formation of the radical anion. In the case of diboranes 4, 5 and 1
      (dimesitylboryl)-8-(diphenylboryl)naphthalene (6), two distinct waves are
      observed at E(1/2)-2.14 and -2.56 V for 4, E(1/2)-2.26 and -2.78 V for 5, and
      E(1/2)-2.41 and -2.84 V for 6. The first reduction wave most likely indicates the
      formation of a radical anion in which the unpaired electron is sigma-delocalized
      over the two boron centers.

PMID- 15252670
TI  - Template synthesis of [(Mo(V)2O4)(O3PCH2PO3)]n clusters (n = 3, 4, 10): solid
      state and solution studies.
AB  - The influence of three exogenous ligands (acetate, formate and carbonate) on the
      condensation process of the [Mo2O4]2+ dioxocation with the [O3PCH2PO3](4-) group
      has been investigated. Four cyclic or bicyclic compounds have been isolated and
      characterized by X-ray diffraction studies. Two closely related acetato and
      formato ovoidal duodecanuclear compounds,
      Na24[Na4(H2O)6[(Mo2O4)10(O3PCH2PO3)10(CH3COO)8(H2O)4]].103H2O (1) and
      Na28[Na2[(Mo2O4)10(O3PCH2PO3)10(HCOO)10]].110H2O (2), respectively, have been
      obtained. Their structures can be described as two interconnected nonequivalent
      wheels, delimiting a large cavity. When the condensation is performed in similar
      conditions but replacing carboxylato groups by carbonato ligands, the ellipsoidal
      octanuclear Na11[Na(H2O)2[(Mo2O4)4(O3PCH2PO3)4(CO3)2]].70H2O (3) compound is
      isolated. 31P NMR spectroscopic studies have shown that complexes 1 and 3 are
      stable in solution at room temperature. Nevertheless, on heating an aqueous
      solution of 3, the Na8[(Mo2O4)3(O3PCH2PO3)3(MoO4)].18H2O (4) complex, free of
      carbonato groups, is obtained. 4 is a hexanuclear Mo(V) wheel encapsulating a
      tetrahedral [Mo(VI)O4](2-) anion. Its rational synthesis using a controlled
      Mo(V)/Mo(VI) ratio is also presented.

PMID- 15252671
TI  - Three-ring, branched cyclam derivatives and their interaction with nickel(II),
      copper(II), zinc(II) and cadmium(II).
AB  - The interaction of two symmetrically branched tris-cyclam derivatives based on
      1,3,5-trimethylenebenzene and phloroglucinol cores with nickel(II), copper(II),
      zinc(II) and cadmium(II) is reported. All four metal ions yield solid complexes
      in which the metal : ligand ratio is 3 : 1. For both ligand types,
      spectrophotometric titrations confirm the formation of nickel(II) and copper(II)
      complexes of similar 3 : 1 stoichiometry in dimethyl sulfoxide. Visible spectral,
      electrochemical, magnetic moment, ESR and NMR studies have been performed to
      probe the nature of the respective complexes. Where appropriate, the results from
      the above metal-ion studies are compared with those from parallel investigations
      in which the corresponding (substituted) mono-cyclam analogues were employed as
      the ligands. A structural determination employing a poorly diffracting crystal of
      the trinuclear nickel(II) complex of the tris-cyclam ligand incorporating a 1,3,5
      trimethylenebenzene core was successfully carried out with the aid of a
      synchrotron radiation source. A nickel ion occupies each cyclam ring in a square
      planar coordination arrangement, with each cyclam ring adopting the stable trans
      III configuration.

PMID- 15252672
TI  - Molecular zinc phosphonates: synthesis and X-ray crystal structures of
      [[(ZnMe)4(THF)2][tBuPO3]2] and [[(ZnEt)3(Zn(THF))3][tBuPO3]4[mu3-OEt]].
AB  - The reactions of zinc alkyls with tert-butylphosphonic acid in 2 : 1 and 1 : 1
      molar ratios afforded [[(ZnMe)(4-)(THF)2][tBuPO3]2] (2) and
      [[(ZnEt)3(Zn(THF))3][tBuPO3]4[mu3-OEt]] (3), respectively. Compounds 2 and 3 have
      been fully characterised by means of spectroscopic and analytical methods. Single
      crystal X-ray diffraction studies revealed that zinc phosphonates 2 and 3 are
      tetra- and hexa-nuclear, respectively. This is in contrast to the dodecanuclear
      zinc phosphonate [[Zn2(THF)2(ZnEt)6Zn4(mu4-O)][(tBuPO3)8]] (1) obtained in a 1.5
      : 1 reaction between zinc alkyls and tBuP(O)(OH)2.

PMID- 15252673
TI  - A centred, elongated "ferric tetrahedron" with an S= 15/2 spin ground state.
AB  - The reaction of anhydrous FeCl(3) with 1H-benzotriazole-1-methanol (Bta-CH(2)OH)
      in MeOH produces the pentanuclear complex
      [Fe(5)O(2)(OMe)(2)(Bta)(4)(BtaH)(MeOH)(5)Cl(5)], containing a distorted
      tetrahedron of four Fe ions centred on a fifth. The central Fe is
      antiferromagnetically coupled to the peripheral Fe ions resulting in an S= 15/2
      spin ground state.

PMID- 15252674
TI  - Selective formation of the [PhP(H)-PPh]- anion in the reaction of PhPHLi with
      MeAlCl(2); synthesis and structure of the unusual tetramer [(PhP(H)-PPh)Li.thf]4.
AB  - The reaction of PhPHLi with MeAlCl(2)(3:1 equivalents) gives the tetramer
      [(PhP(H)-PPh)Li.thf]4, and provides the first direct evidence of a link between
      the reactivity patterns observed for Group 14 and 15 phosphanenides and those of
      Group 13.

PMID- 15252675
TI  - Unusual structural trends in the [MCl3([8]aneSe2)](M = As, Sb, Bi) adducts.
AB  - The structures of the homologous [MCl(3)([8]aneSe(2))](M = As, Sb or Bi;
      [8]aneSe(2)= 1,5-diselenacyclooctane) ladder structures formed from planar
      M(2)Cl(6) units linked by selenoether ligands with trans Se atoms reveal
      unexpected structural patterns--possible reasons for these are discussed.

PMID- 15252676
TI  - Magnetic behavior and Mossbauer spectra of spin-crossover pyrazolate bridged
      dinuclear diiron(II) complexes: X-ray structures of high-spin and low-spin
      [(Fe(NCBH3)(py))2(mu-bpypz)2].
AB  - The synthesis and characterization of new spin-crossover pyrazolato bridged
      dinuclear [(FeII(NCS)(py))2(mu-bpypz)2] and the corresponding cyanotrihydroborato
      kappaN complexes are described together with the X-ray crystal analysis of the
      latter in both the high-spin and low-spin states as well as the variable
      temperature magnetic susceptibility and/or Mossbauer spectra demonstrating the
      spin-crossover which exhibits an one-step process, but not a two-step one
      characteristic of the known bpym bridged dinuclear complexes.

PMID- 15252677
TI  - From the tetra(amino) phosphonium cation, [P(NHPh)4]+, to the tetra(imino)
      phosphate trianion, [P(NPh)4]3-, two-faced ligands that bind anions and cations.
AB  - The tetraanilino phosphonium cation, [P(N(H)Ph)4]+, 1+, is sequentially
      deprotonated by Bu(n)Li in thf. The deprotonation reaction of the chloride
      derivative, Cl, was monitored by (31)P NMR, which revealed the successive
      formation of the neutral [P(N(H)Ph)3(NPh)], 2, the monoanionic [P(N(H)Ph)2(NPh)2]
      , 3-, the dianionic [P(N(H)Ph)(NPh)3]2-, 4(2-), and finally the trianionic
      species [P(NPh)(4)](3-), (3-). Considering the isoelectronic relationship of oxo,
      =O, and imino groups, =NR, as well as hydroxy, -OH, and amino groups, -N(H)R, the
      neutral complex corresponds to phosphoric acid, H3PO4, whereas the anions 3-, 4(2
      ) and 5(3-) are analogues of dihydrogen phosphate, H2PO4-, monohydrogenphosphate,
      HPO4(2-), and orthophosphate ions, PO4(3-), respectively. Solid state structures
      were obtained of 1Cl, 2LiCl(thf)(2), 3Li(thf)(3.5), 3Li(2)Cl(thf)(4.25),
      3Li(2)Cl(thf)(6) and 5Li(4)Cl(thf)(4). All systems provide two separate N-P-N
      chelation sites at opposite ligand faces, either consisting of the di(amino)
      arrangement P(NH)(2), acting as a double H-bond donor, the di(imino) arrangement
      PN(2), donating two electron pairs, or the mixed amino imino arrangement
      P(N)(NH), which supplies both electron pair and H-donor site. Interesting in this
      aspect is the mixed amino imino derivative 3- which has the ability to chelate a
      Lewis acid, such as a metal ion, at one face and a Lewis base, such as an anionic
      or neutral donor at the opposite ligand face. The formation of 1-D aggregates and
      the entrapment of lithium chloride are key characteristics of the supramolecular
      structures of the discussed complexes.

PMID- 15252678
TI  - Characterisation of [Cu4S], the catalytic site in nitrous oxide reductase, by EPR
      spectroscopy.
AB  - The enzyme nitrous oxide reductase (N(2)OR) has a unique tetranuclear copper
      centre [Cu(4)S], called Cu(Z), at the catalytic site for the two-electron
      reduction of N(2)O to N(2). The X- and Q-band EPR spectra have been recorded from
      two forms of the catalytic site of the enzyme N(2)OR from Paracoccus
      pantotrophus, namely, a form prepared anaerobically, Cu(Z), that undergoes a one
      electron redox cycle and Cu(Z)*, prepared aerobically, which cannot be redox
      cycled. The spectra of both species are axial with that of Cu(Z) showing a rich
      hyperfine splitting in the g||-region at X-band. DFT calculations were performed
      to gain insight into the electronic configuration and ground-state properties of
      Cu(Z) and to calculate EPR parameters. The results for the oxidation state
      [Cu(+1)(3)Cu(+2)(1)S](3+) are in good agreement with values obtained from the
      fitting of experimental spectra, confirming the absolute oxidation state of
      Cu(Z). The unpaired spin density in this configuration is delocalised over four
      copper ions, thus, Cu(I) 20.1%, Cu(II) 9.5%, Cu(III) 4.8% and Cu(IV) 9.2%, the
      mu(4)-sulfide ion and oxygen ligand. The three copper ions carrying the highest
      spin density plus the sulfide ion lie approximately in the same plane while the
      fourth copper ion is perpendicular to this plane and carries only 4.8% spin
      density. It is suggested that the atoms in this plane represent the catalytic
      core of Cu(Z), allowing electron redistribution within the plane during
      interaction with the substrate, N(2)O.

PMID- 15252679
TI  - Synthesis, structure and magnetism of new single molecule magnets composed of
      MnII2MnIII2 alkoxo-carboxylate bridged clusters capped by triethanolamine
      ligands.
AB  - A family of tetranuclear mixed-valent Mn(II)(2)/Mn(III)(2) complexes of type
      [Mn(4)(LH(2))(2)(LH)(2)(H(2)O)(x)(RCO(2))(2)](Y)2.nS has been synthesised and
      structurally characterised, where LH(3) = triethanolamine (N(CH(2)CH(2)OH)(3)),
      (R=CH(3), x=2, Y = CH(3)CO(2)-, n=2, S = H(2)O; 1), (R=C(6)H(5), x=0,
      Y=C(6)H(5)CO(2)-, n=1, S = CH(3)CN; 2), (R=C(2)H(5), x=0, Y=ClO(4)(-), n=0; 3). A
      common structural core was deduced from X-ray crystallography and consists of a
      rhomboidal (planar-diamond) array with two 7-coordinate Mn(II) "wingtip (w)"
      centres and two 6-coordinate Mn(III) "body (b)" centres. The Mn(III) ions are
      bridged to the Mn(II) ions by mu3-oxygen atoms from a deprotonated alcohol "arm"
      of each tridentate LH(2-) ligand and by mu2-oxygen atoms from each tetradentate
      LH(2)(-) ligand. The four nitrogen atoms from LH(2-) and LH(2)(-) groups,
      together with bridging and terminal carboxylates oxygens complete the outer
      coordination sites around the Mn atoms. A feature of these clusters is that they
      are linked together in the crystal lattice by hydrogen-bonding interactions
      involving a non-coordinated hydroxyl arm on each LH(2-) group. Detailed DC and AC
      magnetic susceptibility measurements and magnetisation isotherms have been made
      on the three complexes and show that intra-cluster ferromagnetic coupling is
      occurring between the S = 2 Mn(III) and S = 5/2 Mn(II) ions to yield S = 9 ground
      states. The g, J(bb) and J(wb) parameters have been deduced. Inter-cluster
      antiferromagnetic coupling was noted in and this influences the magnetisation
      versus field behaviour and the temperature and magnitude of the out-of-phase AC
      chi"M maxima in comparison to those observed for and. An Arrhenius plot of the
      reciprocal temperature of the maxima in chi"M obtained at different frequencies
      (10 to 1500 Hz), in the range 1.75 K to 4 K, against the natural logarithm of the
      magnetization relaxation rate (1/tau) yielded values of the activation energies
      and pre-exponential factors for two of these new tetranuclear single-molecule
      magnets (SMMs), and. The activation energies were compared with the potential
      energy barrier height, U, for magnetisation direction reversal (U = DS(2)) using
      the axial zero-field splitting parameter, D, deduced from the DC M/H isotherm
      analysis for these S = 9 species. The very small separation of S = 9 and 8 levels
      for these clusters highlights the limitations in the determination of D values
      from M/H data at low temperatures.

PMID- 15252680
TI  - Alkene metatheses in transition metal coordination spheres: dimacrocyclizations
      that join trans positions of square-planar platinum complexes to give
      topologically novel diphosphine ligands.
AB  - The alkene-containing phosphines PPh((CH2)(n)CH=CH2)2)2 are prepared from
      PPhH(2), n-BuLi, and the corresponding bromoalkenes (1:2:2), and combined with
      the platinum tetrahydrothiophene complex [Pt(mu-Cl)(C(6)F(5))(S(CH2CH2(-))2)]2 to
      give the square-planar adducts trans-(Cl)(C(6)F(5))Pt(PPh((CH2)(n)CH=CH2)2)2 (11,
      93-73%; n=a, 2; b, 3; c, 4; d, 5; e, 6; f, 8). Ring-closing metatheses with
      Grubbs' catalyst (2) are studied. With, two isomers of trans-(Cl)(C6F5)[formula:
      see text](14)Ph)(15e) are isolated after hydrogenation. Both form via
      dimacrocyclization between the trans-phosphine ligands, but differ in the
      dispositions of the PPh rings (syn, 31%; anti, 7%). The alternative intraligand
      metathesis product trans-(Cl)(C6F5)[formula: see text](14)Ph)2 (16e) is
      independently prepared by (i) protecting 4e as a borane adduct,
      H(3)B.PPh((CH(2))(6)CH=CH2)2, (ii) cyclization with 2 and hydrogenation to give
      H(3)B[formula: see text] (14), (iii) deprotection and reaction with 12. The
      sample derived from 11e contains < or = 2% 16e; mass spectra suggest that the
      other products are dimers or oligomers. The structures of syn-15e, anti-15e and
      16e are verified crystallographically, and the macrocycle conformations analyzed.
      As expected from the (CH(2))(n) segment length, 11a undergoes intraligand
      metathesis to give (Z,Z)-trans-(Cl)(C6F5)Pt[formula: see text]CH2)2)2 (86%), as
      confirmed by a crystal structure of the hydrogenation product. Although 11b does
      not yield tractable products, 11c gives syn-(E,E)-trans-(Cl)(C6F5[formula:see
      text](21%). This structure, and that of the hydrogenation product (syn-15c; 95%),
      are verified crystallographically. Analogous sequences with 11d,f give syn-15d (5
      and 14% overall).

PMID- 15252681
TI  - Homolysis of the Ln-N (Ln = Yb, Eu) bond. Synthesis, structural characterization
      and catalytic activity of ytterbium(II) and europium(II) complexes with
      methoxyethyl functionalized indenyl ligands.
AB  - The interaction of methoxyethyl functionalized indene compounds (C(9)H(6)-1-R-3
      CH(2)CH(2)OMe, R =t-BuNHSiMe(2)(1), Me(3)Si (2), H (3)) with
      [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5)) produced a series of new
      ytterbium(II) and europium(II) complexes via tandem silylamine
      elimination/homolysis of the Ln-N (Ln=Yb, Eu) bond. Treatment of the
      lanthanide(III) amides [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5)
      with 2 equiv. of, 1,2 and 3, respectively, produced, after workup, the
      ytterbium(II) complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu
      t)](2)Yb(II) (6), (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Yb(II) (7),
      (eta5:eta1-MeOCH(2)CH(2)C(9)H(6))(2)Yb(II)(8) and the corresponding europium(II)
      complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu-t)](2)Eu(II)(9),
      (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Eu(II)(10) and (eta5:eta1
      MeOCH(2)CH(2)C(9)H(6))(2)Eu(II)(11) in moderate to good yield. In contrast,
      interaction of the corresponding indene compounds 1, 2 or 3 with the lanthanide
      amides [(Me(3)Si)(2)N](3)Ln (Ln = Yb, Eu) was not observed, while addition of 0.5
      equiv. of anhydrous LiCl to the corresponding reaction mixture produced, after
      workup, the corresponding ytterbium(II) or europium(II) complexes. All the new
      compounds were fully characterized by spectroscopic and elemental analyses. The
      structures of complexes, and were determined by single-crystal X-ray analyses.
      The catalytic activity of all the ytterbium(II) and europium(II) complexes on MMA
      polymerization was examined. It was found that all the ytterbium(II) and
      europium(II) complexes can function as single-component MMA polymerization
      catalysts. The temperature, solvent and ligand effects on the catalytic activity
      were studied.

PMID- 15252682
TI  - Dinuclear gold(I) complexes of bridging bidentate carbene ligands: synthesis,
      structure and spectroscopic characterisation.
AB  - Eight dinuclear Au(i)-carbene complexes have been synthesized from various
      imidazolium-linked cyclophanes and related acyclic bis(imidazolium) salts, by
      treatment of the imidazolium salts with [Au(i)(SMe(2))Cl] in the presence of a
      carboxylate base. Single crystal structural studies showed that the Au(i)-carbene
      compounds contain dinuclear (AuL)(2) cations in which a pair of gold(i) centres
      are linked by a pair of bridging dicarbenoid ligands. Interestingly, the
      structural studies revealed short AuAu contacts of 3.0485(3)[Angstrom] and
      3.5425(6)[Angstrom] in two of these complexes. NMR studies showed that the
      (AuL)(2) cations constructed from the cyclophane-based ligands retain a
      relatively rigid structure in solution, whilst those of the non-cyclophane ligand
      systems are fluxional in solution. The electronic absorption and emission spectra
      of the complexes in solution at room temperature were recorded and the complex
      with the shortest AuAu contact was found to emit intensely at 400 nm and more
      weakly at 780 nm upon excitation at 260 nm. The compounds with longer AuAu
      separations were not emissive under these conditions.

PMID- 15252683
TI  - Antiferromagnetic coupling between rare earth ions and semiquinones in a series
      of 1:1 complexes.
AB  - We use the strategy of diamagnetic substitution for obtaining information on the
      crystal field effects in paramagnetic rare earth ions using the homologous series
      of compounds with the diamagnetic tropolonato ligand, Ln(Trp)(HBPz(3))(2), and
      the paramagnetic semiquinone ligand, Ln(DTBSQ)(HBPz(3))(2), (DTBSQ = 3,5-di-tert
      butylsemiquinonato, Trp = tropolonate, HBPz(3)= hydrotrispyrazolylborate) for Ln
      = Sm(iii), Eu(iii), Gd(iii), Tb(iii), Dy(iii), Ho(iii), Er(iii) or Yb(iii). The X
      ray crystal structure of a new form of tropolonate derivative is presented, which
      shows, as expected, a marked similarity with the structure of the semiquinonate
      derivative. The Ln(Trp)(HBPz(3))(2) derivatives were then used as a reference for
      the qualitative determination of crystal field effects in the exchange coupled
      semiquinone derivatives. Through magnetisation and susceptibility measurements
      this empirical diamagnetic substitution method evidenced for Er(iii), Tb(iii),
      Dy(iii) and Yb(iii) derivatives a dominating antiferromagnetic coupling. The
      increased antiferromagnetic contribution compared to other radical-rare earth
      metal complexes formed by nitronyl nitroxide ligands may be related to the
      increased donor strength of the semiquinone ligand.

PMID- 15252684
TI  - Kinetics and mechanism of the ferroxime(II)-catalysed biomimetic oxidation of 2
      aminophenol by dioxygen. A functional phenoxazinone synthase model.
AB  - [Fe(Hdmg)(2)(MeIm)(2)](1), referred to as ferroxime(II), is the precursor of a
      selective catalyst for the oxidative dehydrogenation of 2-aminophenol (Hap) to 2
      amino-3H-phenoxazine-3-one (apx) by dioxygen under ambient conditions. The
      superoxoferroxime(III) species has been detected by ES-MS, and a 4-substituted 2
      aminophenoxyl free radical by the ESR technique. The kinetics of the reaction was
      followed spectrophotometrically and by monitoring dioxygen uptake at constant
      pressure. According to the proposed mechanism, solvolysis of 1 is followed by
      O(2) binding to afford a superoxoferroxime, which abstracts an H-atom from Hap in
      the rate-determining step via an H-bonded intermediate, generating the free
      radical. This is supported by the observed primary deuterium kinetic isotope
      effect of 2.63. The system studied is a functional phenoxazinone synthase model.

PMID- 15252685
TI  - Visible absorption spectra of metal-catecholate and metal-tironate complexes.
AB  - Interactions between metals and catechol (1,2-dihydroxybenzene) or other ortho
      dihydroxy moieties are being found in an increasing number of biological systems
      with functions ranging from metal ion internalization to biomaterial synthesis.
      Although metal-catecholate interactions have been studied in the past, we present
      the first systematic study of an array of these compounds, all prepared under
      identical conditions. We report the ultraviolet-visible absorption (UV-vis)
      spectra for catecholate and tironate complexes of the first row transition
      elements. Generation and identification of these species were accomplished by
      preparing aqueous solutions with varied ligand:metal ratios and subsequently
      titrating with base (NaOH). Controlled ligand deprotonation and metal binding
      resulted in sequential formation of complexes with one, two, and sometimes three
      catecholate or tironate ligands bound to a metal ion. We prepared the mono-, bis-
      and tris-catecholates and -tironates of Fe(3+), V(3+), V(4+)and Mn(3+), the mono-
      and bis-catecholates and -tironates of Cu(2+), Co(2+), Ni(2+), Zn(2+), Cr(2+) and
      Mn(2+), and several Ti(4+) and Cr(3+) species. The UV-vis spectra of each complex
      are described, some of which have not been reported previously. These data can
      now be applied to characterization of biological metal-catecholate systems.

PMID- 15252686
TI  - Synthesis, structural and magnetic properties of a series of copper(II) complexes
      containing a monocarboxylated perchlorotriphenylmethyl radical as a coordinating
      open-shell ligand.
AB  - A series of complexes of copper(II)-containing a perchlorotriphenylmethyl radical
      functionalized with a carboxylic group as a new ligand is reported. The compounds
      [Cu(PTMMC)(2)(L)(3)](PTMMC = (tetradecachloro-4-carboxytriphenyl)methyl radical;
      L =(1) H(2)O, (2) pyrimidine and ethanol or (3) pyridine),
      [Cu(2)(PTMMC)(2)(MeCOO)(2)(H(2)O)(2)](4) and [Cu(HPTMMC)(2)(L)(3)](HPTMMC =alpha
      H-(tetradecachlorotriphenyl)methane-4-carboxylic acid; L = pyridine)(5) were
      structurally characterized. In complexes 1, 2, 3, and 5, the copper(II) ion is
      coordinated to two PTMMC (or HPTMMC) units in a slightly distorted square planar
      surrounding, while 4 shows a paddle-wheel copper(II) dimer structure, where each
      Cu metal ion has four O atoms of different carboxylate groups, two of them
      belonging to two PTMMC radicals. The copper(II)-radical exchange couplings are
      antiferromagnetic for complexes 1, 2 and 3. A linear three-spin model was applied
      to complexes 1, 2 and 3 to give J/k(B)=-24.9, -15.0 and -20.7 K, respectively.
      Magnetic properties of 4 show that it is one of the scarce examples of a spin
      frustrated system composed of organic radicals and metal ions. In this case,
      experimental data were fitted to a magnetic model based on a symmetrical
      butterfly arrangement to give a copper(II)-copper(II) exchange coupling of
      J/k(B)=-350.0 K and a copper(II)-radical exchange coupling of J/k(B)=-21.3 K,
      similar to that observed for the copper(II)-radical interactions in complexes,
      and.

PMID- 15252687
TI  - Yttrium complexes incorporating the chelating diamides [ArN(CH2)xNAr]2- (Ar =
      C6H3-2,6-iPr2, x= 2, 3) and their unusual reaction with phenylsilane.
AB  - Novel yttrium chelating diamide complexes [(Y[ArN(CH(2))(x)NAr](Z)(THF)(n))(y)]
      (Z = I, CH(SiMe(3))(2), CH(2)Ph, H, N(SiMe(3))(2), OC(6)H(3)-2,6-(t)Bu(2)-4-Me; x
      = 2, 3; n = 1 or 2; y = 1 or 2) were made via salt metathesis of the potassium
      diamides (x = 3 (3), x = 2 (4)) and yttrium triiodide in THF (5,10), followed by
      salt metathesis with the appropriate potassium salt (6-9, 11-13, 15) and further
      reaction with molecular hydrogen (14). 6 and 11(Z = CH(SiMe(3))(2), x = 2, 3)
      underwent unprecedented exchange of yttrium for silicon on reaction with
      phenylsilane to yield (Si[ArN(CH(2))(x)NAr]PhH) (x = 2 (16), 3) and
      (Si[CH(SiMe(3))(2)]PhH(2)).

PMID- 15252688
TI  - Regioselective HON-addition of bifunctional hydrazone oximes to Pt(IV)-bound
      nitriles.
AB  - Treatment of trans-[PtCl(4)(RCN)(2)](R = Me, Et) with the hydrazone oximes
      MeC(=NOH)C(R')=NNH(2)(R' = Me, Ph) at 45 degrees C in CH(2)Cl(2) led to the
      formation of trans-[PtCl(4)(NH=C(R)ON=C(Me)C(R')=NNH(2))(2)](R/R' = Me/Ph 1,
      Et/Me 2, Et/Ph 3) due to the regioselective OH-addition of the bifunctional
      MeC(=NOH)C(R')=NNH(2) to the nitrile group. The reaction of 3 and
      Ph(3)P=CHCO(2)Me allows the formation of the Pt(II) complex trans
      [PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NNH(2))2](4). In 4, the imine ligand was liberated
      by substitution with 2 equivalents of bis(1,2-diphenylphosphino)ethane (dppe) in
      CDCl(3) to give, along with the free ligand, the solid [Pt(dppe)(2)]Cl(2). The
      free iminoacyl hydrazone, having a restricted life-time, decomposes at 20-25
      degrees C in about 20 h to the parent organonitrile and the hydrazone oxime. The
      Schiff condensation of the free NH(2) groups of 4 with aromatic aldehydes, i.e. 2
      OH-5-NO(2)-benzaldehyde and 4-NO(2)-benzaldehyde, brings about the formation of
      the platinum(II) complexes trans-[PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NN=CH(C(6)H(3)-2
      OH-5-NO(2))2](5) and trans-[PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NN=CH(C(6)H(4)-4
      NO(2))2](6), respectively, containing functionalized remote peripherical groups.
      Metallization of 5, which can be considered as a novel type of metallaligand, was
      achieved by its reaction with M(OAc)(2).nH(2)O (M = Cu, n= 2; M = Co, n= 4) in a
      1:1 molar ratio furnishing solid heteronuclear compounds with composition
      [Pt]:[M]= 1:1. The complexes were characterized by C, H, N elemental analyses,
      FAB+ mass-spectrometry, IR, 1H, 13C[1H] and (195)Pt NMR spectroscopies; X-ray
      structures were determined for 3, 4 and 5.

PMID- 15252689
TI  - A study on oxygen insertion in dinuclear silver cryptates.
AB  - Two novel silver(I) cryptates are reported in this paper.
      [Ag(2)(L(1)O)](ClO(4))(2).H(2)O and [Ag(2)L(1)](ClO(4))(2).1.5H(2)O were
      synthesized by the condensation of tris (3-aminopropyl) amine with m
      phthalaldehyde in the presence of silver(i) ion, under aerobic and anaerobic
      conditions, respectively. (The ligand L(1)O represents the oxygen insertion
      product of L(1).) Cryptates 1, 2 and their hydrogenated ligand H(12)(L(1)O) 3 and
      H(12)L(1) 4 (obtained by reduction of the cryptates) were investigated by
      electrospray mass spectroscopy (ES-MS). 1 and 2 were also decomposed by HCl
      treatment and their products were separated and identified by HPLC and ES-MS. Our
      experiments show that cryptate 2 is able to activate dioxygen that results in
      quantitative aliphatic hydroxylation of L(1) on one of its HC=N bonds. Crystal
      structure analysis shows an interesting difference between 1 and 2 in that 1 is
      an oxygenated and 2 is a non-oxygenated cryptate. Up to date, ligand
      hydroxylation has not been achieved in silver(I) complex-O(2) systems.

PMID- 15252690
TI  - Patterns in abundance and seasonality of insects in the siruvani forest of
      Western ghats, nilgiri biosphere reserve, southern India.
AB  - The seasonal abundance patterns of insects inhabiting the understory vegetation
      of a mixed deciduous forest were examined with the help of the sweep-net sampling
      method. During the study period of 2 years, insects were sampled regularly from
      the understory vegetation of the three selected habitats (moist-deciduous,
      riverine, and teak plantation) of the mixed deciduous forest. Insect abundance
      was maximum in the moist-deciduous habitat and minimum in the teak plantation.
      Generally, insect abundance was the highest during the southwest monsoon in all
      habitats. The temporal pattern of fluctuations in the insect abundance followed
      more or less the same pattern in all the three habitats studied. The insect
      abundance of the understory vegetation varied among the habitats studied, while
      the pattern of seasonal fluctuations in insect abundance was comparable among
      habitats. Composition of the insect community also indicated prominent seasonal
      changes within habitats than interhabitat changes within a season.

PMID- 15252691
TI  - Effect of interactions on the nutrient status of a tropical soil treated with
      green manures and inorganic phosphate fertilizers.
AB  - Integrated nutrient management systems using plant residues and inorganic P
      fertilizers have high potential for increasing crop production and ensuring
      sustainability in the tropics, but their adoption requires in-depth understanding
      of nutrient dynamics in such systems. This was examined in a highly weathered
      tropical soil treated with green manures (GMs) and P fertilizers in two
      experiments conducted in the laboratory and glasshouse. The treatments were
      factorial combinations of the GMs (Calopogonium caeruleum, Gliricidia sepium, and
      Imperata cylindrica) and P fertilizers (phosphate rocks [PRs] from North
      Carolina, China, and Algeria, and triple superphosphate) replicated thrice. Olsen
      P, mineral N, pH, and exchangeable K, Ca, and Mg were monitored in a laboratory
      incubation study for 16 months. The change in soil P fractions and available P
      was also determined at the end of the study. Phosphorus available from the
      amendments was quantified at monthly intervals for 5 months by 33P-32P double
      isotopic labeling in the glasshouse using Setaria sphacelata as test crop. The
      GMs were labeled with 33P to determine their contribution to P taken up by
      Setaria, while that from the P fertilizers was indirectly measured by labeling
      the soil with 32P. The P fertilizers hardly changed Olsen P and exchangeable
      cations during 16 months of incubation. The legume GMs and legume GM+P did not
      change Olsen P, lowered exchangeable Ca, and increased exchangeable K about
      threefold (4.5 cmol[+]kg(-1) soil) in the first 4 months, even as large amounts
      of NH4-N accumulated (approximately 1000 mg kg soil(-1)) and soil pH increased to
      more than 6.5. Afterwards, Olsen P and exchangeable Ca and Mg increased
      (threefold) as NH4+-N and soil pH declined. The legume GMs also augmented
      reversibly sorbed P in Al-P and Fe-P fractions resulting in high residual effect
      in the soil, while fertilizer-P was irreversibly retained. The GMs increased PR-P
      utilization by 40 to over 80%, mobilized soil P, and markedly enhanced uptake of
      N, K, Ca, and Mg. Thus GMs+PRs is an appropriate combination for correcting
      nutrient deficiencies in tropical soils.

PMID- 15252692
TI  - Plastids and stromules interact with the nucleus and cell membrane in vascular
      plants.
AB  - The various metabolic activities of plastids require continuous exchange of
      reactants and products with other organelles of the plant cell. Physical
      interactions between plastids and other organelles might therefore enhance the
      efficiency of plant metabolism. We have observed a close apposition of plastids
      and nuclei in various organs of Nicotiana tabacum and Arabidopsis thaliana. In
      hypocotyl epidermal cells, plastids and stromules, stroma-filled tubular
      extensions of the plastid envelope membrane, were observed to reside in grooves
      and infoldings of the nuclear envelope, indicating a high level of contact
      between the two organelle membranes. In a number of non-green tissues, including
      suspension-cultured cells, perinuclear plastids were frequently associated with
      long stromules that extended from the cell center to the cell membrane. In
      cotyledon petioles, cells lying adjacent to one another frequently contained
      stromules that met on either side of the shared cell wall, suggesting a means of
      intercellular communication. Our results therefore suggest that stromules have
      diverse roles within plant cells, perhaps serving as pathways between nuclei and
      more distant regions of the cell and possibly even other cells.

PMID- 15252693
TI  - Control of development and valepotriate production by auxins in micropropagated
      Valeriana glechomifolia.
AB  - Valeriana glechomifolia is a plant species endemic to southern Brazil that
      accumulates valepotriates, which are terpene derivatives, in all of its organs.
      Valepotriates are the presumed sedative generic components of the
      pharmaceutically used species of Valeriana. The influence of various
      concentrations of the auxins indole-3-acetic acid, indole-3-butyric acid and
      alpha-naphthaleneacetic acid on the growth of micropropagated V. glechomifolia
      was investigated under conditions of transient and continuous exposure. Changes
      in the development of roots and shoots as well as the production of the
      valepotriates acevaltrate, valtrate and didrovaltrate (analyzed by high
      performance liquid chromatography) were evaluated. The best performance in
      valepotriate production, growth and survival under ex vitro conditions following
      plant acclimatization was achieved in the continuous presence of 5.71 microM IAA.
      When cultured in medium containing IAA plants produced stable levels of
      valepotriates throughout the entire cultivation period.

PMID- 15252694
TI  - GISH, AFLP and PCR-RFLP analysis of an intergeneric somatic hybrid combining
      Goutou sour orange and Poncirus trifoliata.
AB  - Intergeneric somatic hybrids combining Goutou sour orange (Citrus aurantium L.)
      with trifoliate orange Poncirus trifoliata (L.) Raf] were produced by
      electrofusion and their genetic inheritance analyzed by amplified fragment length
      polymorphism (AFLP), genomic in situ hybridization (GISH), and PCR-restriction
      fragment length polymorphism (PCR-RFLP). Sixteen mini-calluses were obtained
      after 20 days of culture; they all developed into embryoids on EME500 medium.
      Following several subcultures on shoot induction medium for a total culture
      period of 6 months, shoots regenerated. The plants grew vigorously with a well
      developed root system and exhibited the trifoliate leaf character of P.
      trifoliata. Ploidy analysis verified that all of the regenerates were tetraploids
      (2 n=4 x=36) as expected. GISH analysis confirmed that 18 chromosomes came from
      trifoliate orange and the remaining 18 from Goutou sour orange, as with most
      symmetric somatic hybrid plants; moreover, chromosome translocations were also
      observed in one plant. AFLP analysis of 16 regenerates and their fusion parents
      indicated that all of the somatic hybrids except one were genetically uniform.
      Analysis of the somatic hybrid cytoplasmic genomes with universal primers
      revealed that their chloroplast DNA (cpDNA) banding patterns were identical to
      those of the mesophyll parent trifoliate orange, while their mitochondria (mt)
      genomes were of the callus parent sour orange. The potential of GISH in Citrus
      somatic hybrid analysis is discussed.

PMID- 15252695
TI  - MR imaging of edematous anconeus epitrochlearis: another cause of medial elbow
      pain?
AB  - Two patients with unusual medial elbow pain had MRI scans performed that revealed
      edema of the aberrant muscle of the anconeus epitrochlearis. MRI of this anconeus
      epitrochlearis muscle are presented.

PMID- 15252696
TI  - An enzymatic route to produce pyruvate from lactate.
AB  - A bacterial strain of Acinetobacter sp., which was capable of enzymatic
      production of pyruvate from lactate, was cultured in a 5-l reactor with a basal
      salt medium. After 14 h of fed-batch fermentation, 9.56 g l(-1) cell
      concentration in the broth was obtained with 20 g l(-1) (178 mM) sodium lactate
      and 4 g l(-1) NH(4)Cl in the medium; and the biotransformation ability was 2.51
      units ml(-1). The cells were harvested from one reactor and then used for
      pyruvate production from lactate in the same reactor. l-lactate at a
      concentration about 527 mM was almost stoichiometrically converted to pyruvate in
      28 h. After a total 42 h of cell culture and biotransformation, the
      transformative yield was about 0.72 g g(-1) pyruvate from lactate and the rate of
      pyruvate production was calculated as 1.33 g l(-1) h(-1) during the process. The
      results suggested this simple enzymatic production of pyruvate from lactate
      should be a promising process and may bring a yield higher than that by microbial
      fermentation. By this process, the recovery of pyruvate from such a simple
      reaction liquid is relatively easy and inexpensive to perform.

PMID- 15252697
TI  - Use of activated carbon as a support medium for H2S biofiltration and effect of
      bacterial immobilization on available pore surface.
AB  - The use of support media for the immobilization of microorganisms is widely known
      to provide a surface for microbial growth and a shelter that protects the
      microorganisms from inhibitory compounds. In this study, activated carbon is used
      as a support medium for the immobilization of microorganisms enriched from
      municipal sewage activated sludge to remove gas-phase hydrogen sulfide (H2S), a
      major odorous component of waste gas from sewage treatment plants. A series of
      designed experiments is used to examine the effect on bacteria-immobilized
      activated carbon (termed "biocarbon") due to physical adsorption, chemical
      reaction, and microbial degradation in the overall removal of H2S. H2S
      breakthrough tests are conducted with various samples, including microbe
      immobilized carbon and Teflon discs, salts-medium-washed carbon, and ultra-pure
      water-washed carbon. The results show a higher removal capacity for the microbe
      immobilized activated carbon compared with the activated carbon control in a
      batch biofilter column. The increase in removal capacity is attributed to the
      role played by the immobilized microorganisms in metabolizing adsorbed sulfur and
      sulfur compounds on the biocarbon, hence releasing the adsorption sites for
      further H2S uptake. The advantage for activated carbon serving as the support
      medium is to adsorb a high initial concentration of substrate and progressively
      release this for microbial degradation, hence acting as a buffer for the
      microorganisms. Results obtained from surface area and pore size distribution
      analyses of the biocarbon show a correlation between the available surface area
      and pore volume with the extent of microbial immobilization and H2S uptake. The
      depletion of surface area and pore volume is seen as one of the factors which
      cause the onset of column breakthrough. Microbial growth retardation is due to
      the accumulation of metabolic products (i.e., sulfuric acid); and a lack of water
      and nutrient salts in the batch biofilter are other possible causes of column
      breakthrough.

PMID- 15252698
TI  - Cognitive demand affects the gain of the torsional optokinetic response.
AB  - Cognitive tasks such as mental arithmetic and fixation of imagined targets are
      known to affect vestibular nystagmus. Here we show that another cognitive task
      subject's active control of the rotation of a single moving visual line in an
      otherwise darkened room-influences the gain of the torsional optokinetic response
      to that single moving visual line.

PMID- 15252699
TI  - Retinal projections to the lateral posterior-pulvinar complex in intact and early
      visual cortex lesioned cats.
AB  - In intact cats, it is generally considered that the lateral posterior-pulvinar
      complex (LP-pulvinar) does not receive direct retinal terminals, with the
      exception of the retino-recipient zone known as the geniculate wing. There is,
      however, some evidence that early lesions of the visual cortex can occasionally
      induce the formation of novel retinal projections to the LP nucleus. Given the
      importance of knowing the connectivity pattern of the LP-pulvinar complex in
      intact and lesioned animals, we used the B fragment of cholera toxin, a sensitive
      anterograde tracer, to reinvestigate the retinal projections to the LP-pulvinar
      in normal cats and in cats with early unilateral lesions of the visual cortex
      (areas 17 and 18). Immunohistochemical localization of the toxin was performed to
      show the distribution and morphology of retinofugal terminals. A direct bilateral
      but predominantly contralateral retinal projection reached the caudal portion of
      LPl and LPm in the form of patches located mainly along its dorsomedial surface
      and many scattered terminals. The distribution of retinal projections to LP
      pulvinar in intact and operated cats did not differ. Contrary to what had been
      previously reported, we found no evidence for lesion-induced sprouting of retinal
      axons in these higher-order thalamic nuclei. Retinal input to the LP-pulvinar
      might modulate visual responses driven by primary visual cortex or superior
      colliculus.

PMID- 15252700
TI  - Effects of biomechanical and task constraints on the organization of movement in
      precision aiming.
AB  - Nine participants performed a reciprocal precision aiming task under different
      experimental conditions. Due to the anisotropy of the work space, varying the
      direction of motion (from 0 degrees to 315 degrees in steps of 45 degrees )
      allowed exploration of the effects of biomechanical constraints that were found
      to affect the duration of movement but not the shape of the kinematic pattern.
      Varying the size of the targets to be attained (W: 2.5, 1.25, and 0.625 cm, for a
      constant intertarget distance of 10 cm) and the nature (linear or non-linear) of
      the mapping between effector space (motion of a handheld stylus on a graphics
      tablet) and task space (motion of a pointer between targets on a computer screen)
      also led to changes in movement duration. However, the latter type of constraint
      gave rise to systematic changes in the pattern of movement, with progressively
      more difficult tasks being characterized by progressively less harmonic motion
      patterns. We conclude that in contrast to (biomechanical) constraints at the
      level of the effector, (informational) constraints at the level of the task
      affect the processes underlying movement organization. For the range of values
      studied, the effects of these two types of constraint can be considered to be
      independent.

PMID- 15252701
TI  - Latency of adaptive vergence eye movements induced by vergence-vestibular
      interaction training in monkeys.
AB  - Clear vision of objects that move in depth toward or away from an observer
      requires vergence eye movements. The vergence system must interact with the
      vestibular system to maintain the object images on the foveae of both eyes during
      head movement. Previous studies have shown that training with sinusoidal vergence
      vestibular interaction improves the frequency response of vergence eye movements
      during pitch rotation: vergence eye velocity gains increase and phase-lags
      decrease. To further understand the changes in eye movement responses in this
      adaptation, we examined latencies of vergence eye movements before and after
      vergence-vestibular training. Two head-stabilized Japanese monkeys were rewarded
      for tracking a target spot moving in depth that required vergence eye movements
      of 10 degrees/s. This target motion was synchronized with pitch rotation at 20
      degrees/s. Both target and chair moved in a trapezoidal waveform interspersed
      with random inter-trial intervals. Before training, pitch rotation in complete
      darkness without a target did not induce vergence eye movements. Mean latencies
      of convergence and divergence eye movements induced by vergence target motion
      alone were 182 and 169 ms, respectively. After training, mean latencies of
      convergence and divergence eye movements to a target synchronized with pitch
      rotation shortened to 65 and 53 ms, and vergence eye velocity gains (relative to
      vergence target velocity) at the normal latencies were 0.68 and 1.53,
      respectively. Pitch rotation alone without a target induced vergence eye
      movements with similar latencies after training. These results indicate that
      vestibular information can be used effectively to initiate vergence eye movements
      following vergence-vestibular training.

PMID- 15252702
TI  - The pattern of c-Fos immunoreactivity in the hindbrain of the rat following
      stomach distension.
AB  - It has been previously shown that the walls of the stomach contain vagal and
      splanchnic afferents, connected to low and high threshold (LT and HT) gastric
      receptors, that convey physiological and noxious information to areas of the
      hindbrain involved mainly in the control of gastrointestinal function. Because
      distension of the stomach also reflexly increases the sympathetic drive to the
      cardiovascular system, the present study was planned to examine the pattern of
      activation of all nuclei encountered throughout the hindbrain in response to
      gastric distension. In anaesthetized rats, the stimulus was controlled by
      employing different transmural pressures and frequencies of distension, and c-Fos
      immunohistochemistry was used to characterize neuronal activation. Low intensity
      stimulation induced c-Fos expression in the cranial part of nucleus of solitary
      tract (NTS), the nucleus ambiguus (NA), the lateral reticular area (LRt) and the
      ventrolateral medulla (RVL/CVL). At low frequency of stimulation c-Fos positive
      nuclei (p.n.) were found in NTS only. At high frequency of stimulation an
      increase in c-Fos immunoreactivity was found. High intensity stimulation induced
      c-Fos expression in area postrema (AP), the lateral vestibular nucleus (LVe) and
      the caudal part of the NTS. At low frequency, only the number of c-Fos p.n. was
      increased. Increasing the frequency of stimulation induced c-Fos expression in
      further nuclei such as the parabrachial nucleus (PBN), the inferior olive
      subnuclei (IOn), the oral part of spinal trigeminal nucleus (Sp5O) and locus
      coeruleus (LC). At higher frequencies c-Fos immunoreactivity decreased in NTS and
      LRt, disappeared in VLM and increased in NA. Thus stomach distension activated
      several neuronal excitatory and inhibitory circuits that are involved in the
      control of gastrointestinal function as well as in cardiovascular, respiratory
      and pain regulation. The differences in c-Fos immunoreactivity induced by
      changing the distension patterns suggested interactions between groups of vagal
      and splanchnic afferents.

PMID- 15252703
TI  - Shoulder and elbow joint power differ as a general feature of vertical arm
      movements.
AB  - Consistent patterns of joint power underlie coordinated lower extremity behaviors
      such as running and walking. Recent work found that shoulder and elbow power
      consistently differed during reaching movements in the horizontal plane.
      Moreover, joint power during horizontal reaching appears correlated with motor
      cortical activity. It is not known if the feature of differential joint power
      extends to vertical plane reaches or to reaches of different movement conditions.
      The purpose of this study was to test for differential shoulder and elbow power
      during the acceleratory and deceleratory phases of fast and normal speed vertical
      reaches in sitting and supine positions. Our results suggest that shoulder and
      elbow power typically differed both within and across conditions. First, shoulder
      power values were positive or negative dependent largely on movement direction
      and movement phase. That is, for each direction and phase, the shoulder either
      generated or absorbed energy independent of speed or body position. Second, and
      unexpectedly, reaches of certain condition combinations had similar shoulder
      power magnitudes across directions. In contrast, elbow power values for each
      direction varied between positive and negative values depending on phase, speed
      and position, and no two condition combinations overlapped across directions.
      Third, as target direction, movement phase and body position varied, shoulder
      power at fast and normal speeds were linearly correlated, as was shoulder power
      in sitting and in supine. In contrast, elbow power was linearly correlated only
      between speeds. These results join other studies to suggest that the neuromotor
      control of the shoulder may be less complex as compared to the elbow as a general
      feature of reaching movements. This differential control has important
      implications for the study of reaching impairments in neurorehabilitation
      populations, and provides a potentially important variable in the study of
      cortical firing patterns.

PMID- 15252704
TI  - Pretreatment neurophysiological and clinical characteristics of placebo
      responders in treatment trials for major depression.
AB  - RATIONALE: High placebo response rates are a confound in treatment trials for
      major depressive disorder (MDD). A method for prospective identification of
      placebo responders could enhance the efficiency of clinical trials. OBJECTIVE:
      The objective was to identify the neurophysiological, symptomatic, and cognitive
      characteristics of subjects who were likely to respond to placebo in clinical
      trials for MDD. METHODS: Fifty-one subjects with MDD were treated in clinical
      trials with either fluoxetine ( n=24) or venlafaxine ( n=27) versus placebo. All
      subjects underwent pretreatment assessment with quantitative
      electroencephalographic (QEEG) power and cordance, as well as symptom ratings and
      neuropsychological testing. After a 1-week single-blind placebo lead-in, subjects
      were randomized to double-blind placebo controlled treatment with a medication or
      placebo. At the end of 8 weeks, the blind was broken and treatment response
      assessed. Response was defined by a final Hamilton Depression Rating Scale score
      of </=10. RESULTS: Of the medication-treated and placebo-treated subjects, 52%
      (13/25) and 38% (10/26) responded. Placebo responders had lower pretreatment
      frontocentral cordance in the theta frequency band than all other subjects (
      P<0.006) and medication responders in particular ( P<0.004). Placebo responders
      also had faster cognitive processing time, as assessed by neuropsychological
      testing, and lower reporting of late insomnia ( P<0.03). Exploratory examination
      of a multiple variable model for predicting placebo response was conducted using
      logistic regression, in which these three pretreatment measures accurately
      identified 97.6% of eventual placebo responders. CONCLUSIONS: These findings
      suggest that combined clinical, neurophysiological, and cognitive assessments of
      prospective subjects for clinical trials may be useful for identifying MDD
      subjects who are likely to show robust response to placebo. Prospective
      validation of these results in a larger, independent sample of subjects is
      necessary to establish the reliability and usefulness of this method for
      prospective identification of placebo responders.

PMID- 15252705
TI  - Modulation of nicotine-induced attentional enhancement in rats by adrenoceptor
      antagonists.
AB  - RATIONALE: Understanding the neuropharmacological mechanisms mediating
      attentional enhancement by nicotine would help a targeted search for nicotinic
      compounds with retained therapeutic but reduced unwanted side-effects. Previous
      studies suggested that the dopamine-releasing effects of nicotine may not be of
      primary importance for its attention-enhancing properties. OBJECTIVES: The
      present study examined the role of noradrenergic neurotransmission for the
      effects of nicotine on different response indices of an attentional paradigm.
      METHODS: The effects of systemic injections of the alpha(1)-adrenoceptor
      antagonist prazosin that also displays significant affinity at alpha(2B) and
      alpha(2C)-adrenoceptors and the beta-adrenoceptor antagonist propranolol were
      tested in both the presence and absence of nicotine in rats trained in a version
      of the five-choice serial reaction time task. RESULTS: Nicotine generally
      enhanced the accuracy of signal detection, reduced omission errors and shortened
      response latencies. At the largest doses tested, both prazosin (1 mg/kg) and
      propranolol (10 mg/kg) impaired performance. For propranolol, these effects
      depended on the rate of target signal presentation. The two compounds
      differentially modulated the effects of nicotine. Propranolol (6 mg/kg and 10
      mg/kg) but not prazosin reduced its effects on omission errors and accuracy. By
      contrast, prazosin (0.5 mg/kg) reversed the nicotine-induced reductions in
      response latency. CONCLUSIONS: The data provide the first evidence that beta
      adrenoceptors are involved in mediating the effects of nicotine on signal
      detection, while activation of alpha-adrenoceptors may contribute to its effects
      on response speed. This is a further indication that, from among nicotine's wide
      range of neuropharmacological effects, specific facets can be dissociated that
      are responsible for its attention-enhancing properties.

PMID- 15252706
TI  - Purification and characterization of ferredoxin-NADP+ reductase encoded by
      Bacillus subtilis yumC.
AB  - From Bacillus subtilis cell extracts, ferredoxin-NADP+ reductase (FNR) was
      purified to homogeneity and found to be the yumC gene product by N-terminal amino
      acid sequencing. YumC is a approximately 94-kDa homodimeric protein with one
      molecule of non-covalently bound FAD per subunit. In a diaphorase assay with 2,6
      dichlorophenol-indophenol as electron acceptor, the affinity for NADPH was much
      higher than that for NADH, with Km values of 0.57 microM vs >200 microM. Kcat
      values of YumC with NADPH were 22.7 s(-1) and 35.4 s(-1) in diaphorase and in a
      ferredoxin-dependent NADPH-cytochrome c reduction assay, respectively. The cell
      extracts contained another diaphorase-active enzyme, the yfkO gene product, but
      its affinity for ferredoxin was very low. The deduced YumC amino acid sequence
      has high identity to that of the recently identified Chlorobium tepidum FNR. A
      genomic database search indicated that there are more than 20 genes encoding
      proteins that share a high level of amino acid sequence identity with YumC and
      which have been annotated variously as NADH oxidase, thioredoxin reductase,
      thioredoxin reductase-like protein, etc. These genes are found notably in gram
      positive bacteria, except Clostridia, and less frequently in archaea and
      proteobacteria. We propose that YumC and C. tepidum FNR constitute a new group of
      FNR that should be added to the already established plant-type, bacteria-type,
      and mitochondria-type FNR groups.

PMID- 15252707
TI  - Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal
      women: results from the Women's Health Initiative Hormone Trial.
AB  - AIMS/HYPOTHESIS: Studies examining the effect of postmenopausal hormone therapy
      on concentrations of glucose, insulin and diabetes incidence have been
      inconclusive, in part because many of the studies were too small. We examined the
      effect of oestrogen plus progestin on diabetes incidence and insulin resistance.
      METHODS: The study was a randomised, double-blind trial comparing the effect of
      daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone
      acetate with that of placebo during 5.6 years of follow-up. The participants were
      15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone
      Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes
      incidence was ascertained by self-report of treatment with insulin or oral
      hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were
      measured in a random sample at baseline and at 1 and 3 years. RESULTS: The
      cumulative incidence of treated diabetes was 3.5% in the hormone therapy group
      and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004).
      There was little change in the hazard ratio after adjustment for changes in BMI
      and waist circumference. During the first year of follow-up, changes in fasting
      glucose and insulin indicated a significant fall in insulin resistance in
      actively treated women compared to the control subjects (Year 1 to baseline
      between-group difference -0.22+/-0.10, p=0.03). INTERPRETATIONS/CONCLUSION: These
      data suggest that combined therapy with oestrogen and progestin reduces the
      incidence of diabetes, possibly mediated by a decrease in insulin resistance
      unrelated to body size. Future studies of alternative postmenopausal hormone
      therapy regimens and selective oestrogen agonists and/or antagonists should
      consider the effects of these regimens on insulin resistance and diabetes.

PMID- 15252708
TI  - Transgenic rice plants expressing the snowdrop lectin gene (gna) exhibit high
      level resistance to the whitebacked planthopper (Sogatella furcifera).
AB  - Transgenic rice plants, expressing snowdrop lectin [Galanthus nivalis agglutinin
      (GNA)], obtained by Agrobacterium-mediated genetic transformation, were evaluated
      for resistance against the insect, the whitebacked planthopper (WBPH). The
      transgene gna was driven by the phloem-specific, rice-sucrose synthase promoter
      RSs1, and the bar was driven by the CaMV 35S promoter. In our previous study, the
      transgenic status of these lines was confirmed by Southern, Northern and Western
      blot analyses. Both the transgenes, gna and bar, were stably inherited and co
      segregated into progenies in T1 to T5 generations. Insect bioassays on transgenic
      plants revealed the potent entomotoxic effects of GNA on the WBPH. Also,
      significant decreases were observed in the survival, development and fecundity of
      the insects fed on transgenic plants. Furthermore, intact GNA was detected in the
      total proteins of WBPHs fed on these plants. Western blot analysis revealed
      stable and consistent expression of GNA throughout the growth and development of
      transgenic plants. Transgenic lines expressing GNA exhibited high-level
      resistance against the WBPH. As reported earlier, these transgenics also showed
      substantial resistance against the brown planthopper and green leafhopper.

PMID- 15252709
TI  - [The transobturator tape (TOT). A minimally-invasive procedure for the treatment
      of female urinary stress incontinence].
AB  - The transobturator tape, a new technique for the treatment of female urinary
      stress incontinence, was evaluated with a 1 year follow-up.A total of 124
      patients were treated with a low elasticity polypropylene tape according to the
      technique described by Delorme. The operative procedure is described step by
      step. All patients were followed-up after 3, 6 and 12 months. No intra-operative
      complications were observed. After 12 months 88.7% of the patients were cured and
      an additional 6.4% showed improvement. The transobturator technique (from
      exterior to interior) is, given proven indications and an exact consideration of
      the instructions, a simple, safe and efficient surgical procedure for the
      treatment of female urinary stress incontinence. The technique avoids
      complications such as bladder, intestinal and vascular lesions. It is suitable
      for genuine incontinence and patients with recurrent stress incontinence.

PMID- 15252710
TI  - [Diagnostics and treatment strategies for soft tissue sarcomas].
AB  - Soft tissue sarcomas (STS) represent a rare entity of all malignant tumors (1%).
      Thus, an in-depth understanding of multidisciplinary treatment strategies may not
      be sufficiently present at all operative units. Consecutively, optimal diagnostic
      and therapeutical pathways may not be applied. Magnetic resonance imaging (MRI)
      is the procedure of choice in diagnosing STS. Biopsies should be performed in
      specialized centers. Identification of cytogenetic factors has become more
      important for the typing and prognosis of STS. Management of STS should employ
      multimodal treatment concepts (Oncology, Radiotherapy, Surgical Oncology). The
      decision on whether radiotherapy, chemotherapy or another option is indicated
      should be taken by an interdisciplinary tumor board, which also determines the
      sequence of treatment in relation to resection. To obtain sufficient information
      from histopathologic examination of the resected tumor, a clear and distinct
      definition of critical margins and topography by the surgeon is essential.
      Following these concepts, optimal local tumor control associated with resections
      preserving function and limbs is achieved without impairment of overall
      prognosis. Tumor resection alone, without previous evaluation and where
      appropriate adopting multimodal treatment strategies, no longer meets modern
      standards. After primary treatment is complete, patients have to be enrolled in a
      standardized follow-up program.

PMID- 15252711
TI  - [Isolated extremity perfusion with TNF-alpha and melphalan in unresectable soft
      tissue sarcoma. Indications, principles and technique].

PMID- 15252712
TI  - [Heavy diarrhea by low malignant B cell lymphoma].
AB  - A 52-year old female presented with a low, malignant centroblastic-centrocytic
      lymphoma. After splenectomy and under steroid therapy it came to the eruption of
      a latent Strongyloides stercoralis infection, which the patient had presumably
      been suffering from for several years. Due to the immunodeficient condition and
      under continued steroid therapy even three courses of high dose anthelmintic
      therapy could not eradicate the parasites. The patient died of fulminant sepsis.

PMID- 15252713
TI  - [AT(1) blocker for post-infarct therapy. VALIANT Study].

PMID- 15252714
TI  - [The clinical value of Holter ECG recording].
AB  - The Holter ECG is a well established clinical tool to document intermittent
      arrhythmias. The main indications are palpitations and syncope. However, the
      occurrence of these events during 24 h recording is very rare. So, it is often a
      matter of definition, what findings can speculatively "explain" a syncope.
      Therefore, an event recorder is often more successful. In addition, in patients
      with organic heart disease and reduced left ventricular function invasive
      electrophysiologic testing may be more appropriate. In these cases prophylactic
      implantation of an ICD may be indicated to prevent sudden death. So, in many
      instances the clinical value of Holter recording is overestimated.

PMID- 15252716
TI  - [Health problems due to night shift work and jetlag].
AB  - Technical demands, economic considerations and allocation of services around the
      clock bring about, that night work constantly represents a portion of 12-15% in
      Germany. Work against the biologic clock increases the risks for accidents and
      may produce health risks as sleeping or gastro-intestinal disorders, depression,
      cardio-vascular diseases, overweight, and a disturbed sexual activity and
      fertility. Adaptation to an altered day/night rhythm during night shift work
      takes more than a week, and even then the time shift is rarely complete. In
      contrast the duration of time shift is much shorter during a jetlag and is mostly
      completed after 2-3 days. Therefore, much less health risk is to be expected from
      jetlag as compared to night shift work. About 15% of all healthy adults are
      insufficiently adaptable to night shift work. These individuals carry a
      particularly high health risk, if regularly participating in night shift work.

PMID- 15252717
TI  - Characterization of mesentericin ST99, a bacteriocin produced by Leuconostoc
      mesenteroides subsp. dextranicum ST99 isolated from boza.
AB  - Lactic acid bacteria isolated from Boza, a cereal-fermented beverage from
      Belogratchik, Bulgaria, were screened for the production of bacteriocins. With
      the first screening, 13 of the 52 isolates inhibited the growth of Listeria
      innocua and Lactobacillus plantarum. The cell-free supernatant of one of these
      strains, classified as Leuconostoc mesenteroides subsp. dextranicum ST99,
      inhibited the growth of Bacillus subtilis, Enterococcus faecalis, several
      Lactobacillus spp., Lactococcus lactis subsp. cremoris, Listeria innocua,
      Listeria monocytogenes, Pediococcus pentosaceus, Staphylococcus aureus and
      Streptococcus thermophilus. Clostridium spp., Carnobacterium spp., L.
      mesenteroides and Gram-negative bacteria were not inhibited. Maximum
      antimicrobial activity, i.e. 6,400 arbitrary units (AU)/ml, was recorded in MRS
      broth after 24 h at 30 degrees C. Incubation in the presence of protease IV and
      pronase E resulted in loss of antimicrobial activity, confirming that growth
      inhibition was caused by a bacteriocin, designated here as mesentericin ST99. No
      loss in activity was recorded after treatment with alpha-amylase, SDS, Tween 20,
      Tween 80, urea, Triton X-100, N-laurylsarcosin, EDTA and
      phenylmethylsulfonylfluoride. Mesentericin ST99 remained active after 30 min at
      121 degrees C and after 2 h of incubation at pH 2 to 12. Metabolically active
      cells of L. innocua treated with mesentericin ST99 did not undergo lysis.
      Mesentericin ST99 did not adhere to the cell surface of strain ST99.
      Precipitation with ammonium sulfate (70% saturation), followed by Sep-Pack C18
      chromatography and reverse-phase HPLC on a C18 Nucleosil column yielded one
      antimicrobial peptide.

PMID- 15252718
TI  - Thermostable xylanase10B from Clostridium acetobutylicum ATCC824.
AB  - The Clostridium acetobutylicum xylanase gene xyn10B (CAP0116) was cloned from the
      type strain ATCC 824, whose genome was recently sequenced. The nucleotide
      sequence of C. acetobutylicum xyn10B encodes a 318-amino acid protein. Xyn10B
      consists of a single catalytic domain that belongs to family 10 of glycosyl
      hydrolases. The enzyme was purified from recombinant Escherichia coli. The Xyn10B
      enzyme was highly active toward birchwood xylan, oat-spelt xylan, and moderately
      active toward avicel, carboxymethyl cellulose, polygalacturonic acid, lichenan,
      laminarin, barley-beta-glucan and various p-nitrophenyl monosaccharides. Xyn10B
      hydrolyzed xylan and xylooligosaccharides to produce xylobiose and xylotriose.
      The pH optimum of Xyn10B was 5.0, and the optimal temperature was 70 degrees C.
      The enzyme was stable at 60 degrees C at pH 5.0-6.5 for 1 h without substrate.
      This is one of a number of xylan-related activities encoded on the large plasmid
      in C. acetobutylicum ATCC 824.

PMID- 15252719
TI  - An ethanologenic yeast exhibiting unusual metabolism in the fermentation of
      lignocellulosic hexose sugars.
AB  - Three lignocellulosic substrate mixtures [liquid fraction of acid-catalyzed steam
      exploded softwood, softwood spent sulfite liquor (SSL) and hardwood SSL] were
      separately fermented by the industrially employed SSL-adapted strain Tembec T1
      and a natural galactose-assimilating isolate (Y-1528) of Saccharomyces cerevisiae
      to compare fermentative efficacy. Both strains were confirmed as S. cerevisiae
      via molecular genotyping. The performance of strain Y-1528 exceeded that of
      Tembec T1 on all three substrate mixtures, with complete hexose sugar consumption
      ranging from 10 to 18 h for Y-1528, vs 24 to 28 h for T1. Furthermore, Y-1528
      consumed galactose prior to glucose and mannose, in contrast to Tembec T1, which
      exhibited catabolite repression of galactose metabolism. Ethanol yields were
      comparable regardless of the substrate utilized. Strains T1 and Y-1528 were also
      combined in mixed culture to determine the effects of integrating their distinct
      metabolic capabilities during defined hexose sugar and SSL fermentations. Sugar
      consumption in the defined mixture was accelerated, with complete exhaustion of
      hexose sugars occurring in just over 6 h. Galactose was consumed first, followed
      by glucose and mannose. Ethanol yields were slightly reduced relative to pure
      cultures of Y-1528, but normal growth kinetics was not impeded. Sugar consumption
      in the SSLs was also accelerated, with complete utilization of softwood- and
      hardwood-derived hexose sugars occurring in 6 and 8 h, respectively. Catabolite
      repression was absent in both SSL fermentations.

PMID- 15252721
TI  - Detection and identification of Rickettsia helvetica and Rickettsia sp. IRS3/IRS4
      in Ixodes ricinus ticks found on humans in Spain.

PMID- 15252720
TI  - SARS: responding to an unknown virus.
AB  - The severe acute respiratory syndrome (SARS) is an emerging infection caused by a
      novel coronavirus which first appeared in southern China at the end of 2002. In
      early 2003, through a single incident, it spread to Hong Kong, Singapore, Canada
      and Vietnam. For busy clinicians in large public hospitals, the response to the
      virus was initially based on ensuring a high level of protection for staff.
      However, as the epidemic progressed and more information became available about
      the virus, procedures were rationalized and the virus is currently under control
      worldwide. There are, however, numerous unanswered questions concerning super
      spreading events, the modes of transmission of the virus and, perhaps most
      importantly, the rapid detection of the virus early in the course of disease.
      These issues need to be addressed in case the virus becomes more widespread in
      the near future.

PMID- 15252722
TI  - Common founder effect of rapsyn N88K studied using intragenic markers.
AB  - Mutations in the human gene encoding rapsyn have been linked to a recessive form
      of postsynaptic congenital myasthenic syndrome due to deficient clustering of
      acetylcholine receptors at the endplate. All patients reported to date carry the
      N88K mutation, suggesting a possible common founder effect. To decrease the
      likelihood of a recombination event occurring within the span of neighboring
      microsatellite markers, we used seven intragenic single nucleotide polymorphisms
      (SNPs) spanning 8 kb to characterize the haplotype associated with N88K. In three
      affected N88K homozygous individuals, we identified a common haplotype present in
      all heterozygous carriers of N88K. Of note, in two asymptomatic N88K homozygous
      individuals, a second haplotype was present that differed at three SNP sites
      downstream from the N88K mutation. Our findings of a common haplotype associated
      with the N88K mutation support a founder effect. The discordant haplotype found
      in homozygous individuals suggests that recombination events may have occurred
      within the rapsyn gene and that this may have implications in the phenotypic
      expression of the disease.

PMID- 15252723
TI  - Trisomy 1 in a case of a missed abortion.
AB  - Most chromosomal trisomies lead to miscarriages. In all trisomies, trisomy 1 is
      the most rare case. We herein present a patient who demonstrated a gestational
      sac and a yolk sac on transvaginal ultrasound. However, at 53 days of gestation,
      the pregnancy was lost with a diagnosis of a blighted ovum. A D&C was recommended
      and performed. A cytogenetic analysis from chorionic villi demonstrated a
      47,XX,+1 chromosome complement in all 100 cells. Regarding full trisomy 1, there
      has only been one case report of a preembryo and two case reports in a clinically
      recognized pregnancy to date.

PMID- 15252725
TI  - [Patient careers. Facial pain and neuralgias].
AB  - The correct diagnosis in patients with facial pain is essential to avoid
      erroneous diagnostic and therapeutic measures. Trigeminal neuralgia is easily
      recognized by the typical history given by the patient. Treatment of first choice
      is carbamazepine. When pharmacological treatment fails, surgical options are
      available. Tolosa Hunt syndrome is judged to be caused by a granulomatous
      infiltration in the cavernous sinus, treatment consists in corticosteroids.
      Painful craniomandibular disorders are often mistaken for 'atypical facial pain'.
      Atypical facial pain, now called 'persistent idiopathic facial pain' should only
      be diagnosed after thorough exclusion of all known primary and symptomatic facial
      pain syndromes. Treatment consists mainly in patient education, in the avoidance
      of further surgical interventions, and in pharmacotherapy with tricyclic
      antidepressants. A thorough history and examination are crucial to correctly
      classify these facial pain syndromes.

PMID- 15252724
TI  - Diversity and cold-active hydrolytic enzymes of culturable bacteria associated
      with Arctic sea ice, Spitzbergen.
AB  - The diversity of culturable bacteria associated with sea ice from four
      permanently cold fjords of Spitzbergen, Arctic Ocean, was investigated. A total
      of 116 psychrophilic and psychrotolerant strains were isolated under aerobic
      conditions at 4 degrees C. The isolates were grouped using amplified rDNA
      restriction analysis fingerprinting and identified by partial sequencing of 16S
      rRNA gene. The bacterial isolates fell in five phylogenetic groups: subclasses
      alpha and gamma of Proteobacteria, the Bacillus-Clostridium group, the order
      Actinomycetales, and the Cytophaga-Flexibacter-Bacteroides (CFB) phylum. Over 70%
      of the isolates were affiliated with the Proteobacteria gamma subclass. Based on
      phylogenetic analysis (<98% sequence similarity), over 40% of Arctic isolates
      represent potentially novel species or genera. Most of the isolates were
      psychrotolerant and grew optimally between 20 and 25 degrees C. Only a few
      strains were psychrophilic, with an optimal growth at 10-15 degrees C. The
      majority of the bacterial strains were able to secrete a broad range of cold
      active hydrolytic enzymes into the medium at a cultivation temperature of 4
      degrees C. The isolates that are able to degrade proteins (skim milk, casein),
      lipids (olive oil), and polysaccharides (starch, pectin) account for,
      respectively, 56, 31, and 21% of sea-ice and seawater strains. The temperature
      dependences for enzyme production during growth and enzymatic activity were
      determined for two selected enzymes, alpha-amylase and beta-galactosidase.
      Interestingly, high levels of enzyme productions were measured at growth
      temperatures between 4 and 10 degrees C, and almost no production was detected at
      higher temperatures (20-30 degrees C). Catalytic activity was detected even below
      the freezing point of water (at -5 degrees C), demonstrating the unique
      properties of these enzymes.

PMID- 15252726
TI  - [The trigemino-cervical complex. Integration of peripheral and central pain
      mechanisms in primary headache syndromes].
AB  - The activation of the trigeminal nociceptive system is the neural substrate of
      pain in primary headache syndromes such as migraine and cluster headache. The
      nociceptive inflow from the meninges to the spinal cord is relayed in brainstem
      neurones of the trigemino-cervical complex (TCC). Two important mechanisms of
      pain transmission are reviewed: convergence of nociceptive trigeminal and
      cervical afferents and sensitization of trigemino-cervical neurones. These
      mechanisms have clinical correlates such as hyperalgesia, allodynia, spread and
      referral of pain to trigeminal or cervical dermatomes. Neurones in the TCC are
      subject to a modulation of pain-modulatory circuits in the brainstem such as the
      periaqueductal grey (PAG). Recent experimental and clinical findings of a
      modulation of these pain processes are discussed. The review focuses on TCC
      neurones as integrative relay neurones between peripheral and central pain
      mechanisms. The understanding of these mechanisms has implications for the
      understanding of the clinical phenomenology in primary headache syndromes and the
      development of therapeutical options.

PMID- 15252727
TI  - Environmental gradients and herbivore feeding preferences in coastal salt
      marshes.
AB  - Current theories of plant-herbivore interactions suggest that plants may differ
      in palatability to herbivores as a function of abiotic stress; however, studies
      of these theories have produced mixed results. We compared the palatability of
      eight common salt marsh plants that occur across elevational and salinity stress
      gradients to six common leaf-chewing herbivores to determine patterns of plant
      palatability. The palatability of every plant species varied across gradients of
      abiotic stress in at least one comparison, and over half of the comparisons
      indicated significant differences in palatability. The direction of the
      preferences, however, was dependent on the plant and herbivore species studied,
      suggesting that different types of stress affect plants in different ways, that
      different plant species respond differently to stress, and that different
      herbivore species measure plant quality in different ways. Overall, 51% of the
      variation in the strength of the feeding preferences could be explained by a
      knowledge of the strength of the stress gradient and the type of gradient, plant
      and herbivore studied. This suggests that the prospects are good for a more
      complex, conditional theory of plant stress and herbivore feeding preferences
      that is based on a mechanistic understanding of plant physiology and the factors
      underlying herbivore feeding preferences.

PMID- 15252728
TI  - Inbreeding influences herbivory in Cucurbita pepo ssp. texana (Cucurbitaceae).
AB  - In a series of field experiments Diabrotica beetle herbivory was found to
      influence the magnitude of inbreeding depression in Cucurbita pepo ssp. texana,
      an annual monoecious vine. Beetles damage flowers and fruits and chew dime-sized
      holes in leaf tissue between major veins. Inbred plants were found to be more
      likely to be damaged by beetles and to have more leaves damaged per plant than
      outcrossed plants. A positive linear association was found between the
      coefficient of inbreeding and the magnitude of leaf damage, whereas a negative
      association was found between coefficient of inbreeding and several male and
      female fitness traits. When pesticides were used to control beetle herbivory, the
      interaction between coefficient of inbreeding and pesticide treatment was
      significant for fruit production and marginally significant for pollen quantity
      per anther. Therefore, the magnitude of inbreeding depression in C. pepo ssp.
      texana varies depending on the severity of beetle herbivory.

PMID- 15252729
TI  - Competing for crevices: interspecific conflict influences retreat-site selection
      in montane lizards.
AB  - Direct interference competition between sympatric taxa affects habitat use and
      shelter-site selection in species within most major vertebrate lineages. However,
      studies on interspecific social interference in reptiles largely have been
      confined to research on interactions between non-native (invasive) species and
      native fauna. Does interspecific interference also influence habitat use within
      natural assemblages of reptiles? We studied five broadly sympatric species of
      viviparous montane skinks within the genera Egernia and Eulamprus in southeastern
      Australia. Previous work has shown strong interspecific overlap in abiotic
      attributes of shelter-sites for these taxa, but no joint occupancy of retreats.
      Laboratory trials in which we manipulated the identity of co-occurring lizards
      revealed frequent displacement from "preferred" (hotter) shelters, with
      interspecific interactions more intense than intraspecific conflicts. The five
      species displayed a linear interspecific dominance hierarchy, with larger species
      displacing smaller taxa. Field manipulations confirmed that interspecific
      interactions between these species affect shelter-site use. We conclude that
      direct agonistic encounters between individuals of different species strongly
      influence habitat use by lizards within this assemblage.

PMID- 15252730
TI  - Ovoinhibitor in the chicken bursa of Fabricius: identification, isolation, and
      localization.
AB  - A monoclonal antibody (Mab) developed against a partially purified bursal protein
      extract was found to bind specifically to a single cell type in the cortico
      medullary border region of the chicken bursa of Fabricius. These cells were
      microscopically similar to the bursal secretory dendritic-like cells. A product
      with an apparent molecular weight of approximately 56 kDa on SDS-polyacrylamide
      gel electrophoresis was immunopurified from bursal extracts by utilizing this
      Mab. This product was subjected to peptide digestion and protein sequencing. The
      two resulting sequences perfectly matched the known sequence of chicken
      ovoinhibitor. Gene-specific polymerase chain reaction (PCR) primers were designed
      for the ovoinhibitor, RNA was purified from chicken bursae, and reverse
      transcription/PCR was performed. Two amplicons with the expected size for
      ovoinhibitor mRNA were obtained. These data suggest that the gene for
      ovoinhibitor is expressed in the bursa of Fabricius, and that the bursal
      secretory dendritic-like cells may be a previously unreported source of
      ovoinhibitor.

PMID- 15252731
TI  - Cell proliferation during the early stages of human eye development.
AB  - The distribution as well as the ultrastructural and biochemical characteristics
      of proliferating cells in the human eye were investigated in five conceptuses of
      5-9 postovulatory weeks, using morphological techniques and Ki-67 immunostaining.
      The Ki-67 nuclear protein was used as a proliferation marker because of its
      expression in all phases of the cell cycle except the resting phase (G0). The
      labelling indices of Ki-67-positive cells were analysed by means of the Kruskal
      Wallis ANOVA test and the Wilcoxon matched-pairs test. In the 5th week, mitotic
      cells were the most numerous between the two layers of the optic cup, the optic
      cup and stalk, and between the lens pit and the surface ectoderm. During the 6th
      week, cells were observed in the lens epithelium covering the whole cavity of the
      lens vesicle as well as in the neuroblast zone and the pigmented epithelium of
      the retina. At later stages (7th-9th weeks), Ki-67-positive cells were restricted
      to the anterior lens epithelium, the outer neuroblast zone, and the pigmented
      retina. Throughout all stages examined, mitotic figures were found lying
      exclusively adjacent to the intraretinal space. Early in the lens pit, they were
      confined to the free epithelial surface, and later were facing the cavity of the
      lens vesicle. The proliferative activity was the most intensive in the 6th week,
      whereas it decreased significantly in the later stages. Additionally, when
      proliferative activities were compared, the peripheral retina appeared to be less
      mature than the central before the 9th week. In the earliest analysed stage, cell
      proliferation might be associated with the sculpturing of the optic cup and
      stalk, the cornea, and the lens. In the 6th week, the most intensive
      proliferation seems to be involved not only in the further morphogenesis of the
      optic cup and the lens vesicle but also in the retinal neurogenesis. At later
      stages, the decreased proliferation might participate in the neurogenesis of the
      outer neuroblast zone and the secondary lens fibre formation.

PMID- 15252732
TI  - Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid.
AB  - Oncocytic cell tumors (OCTs) of the thyroid include oncocytic cell adenomas
      (OCAs) and oncocytic cell carcinomas (OCCs). Oncocytic variant of papillary
      carcinoma (OVPC) has also been described. These tumors may present similar
      diagnostic problems as their non-oncocytic counterparts, in both conventional
      histology and fine-needle aspiration biopsies. Several markers were shown able to
      distinguish benign from malignant thyroid follicular tumors, galectin-3 and HBME
      1 being the most promising ones. Controversial data have been reported on their
      discriminatory potential in the small series of OCTs so far analyzed. We aimed to
      assess the role of galectin-3 and HBME-1 in a large series of 152 OCTs (including
      50 OCAs, 70 OCCs and 32 OVPCs). The expression of PPARgamma protein was also
      evaluated. Using a biotin-free detection system, the sensitivity of galectin-3
      was 95.1%, while that for HBME-1 was nearly 53%. The combination of galectin-3
      and HBME-1 increased the sensitivity up to 99%. However, for both markers, the
      specificity was 88%, lower than that reported for non-oncocytic follicular
      tumors. PPARgamma protein overexpression was absent in all OCAs tested and
      present in only 10% of OCCs, confirming previous reports on the low prevalence of
      PAX8-PPARgamma translocations in OCT and ruling out its role as a potential
      diagnostic marker of malignancy.

PMID- 15252733
TI  - C-Terminal 23 kDa polypeptide of soybean Gly m Bd 28 K is a potential allergen.
AB  - Gly m Bd 28 K is a major soybean (Glycine max Merr.) glycoprotein allergen. It
      was originally identified as a 28 kDa polypeptide in soybean seed flour. However,
      the full-length protein is encoded by an open reading frame (ORF) of 473 amino
      acids, and contains a 23 kDa C-terminal polypeptide of as yet unknown allergenic
      and structural characteristics. IgE-binding (allergenic potential) of the Gly m
      Bd 28 K protein including the 23 kDa C-terminal portion as well as shorter
      fragments derived from the full-length ORF were evaluated using sera from soy
      sensitive adults. All of these sera contained IgE that efficiently recognized the
      C-terminal region. Epitope mapping demonstrated that a dominant linear C-terminal
      IgE binding epitope resides between residues S256 and A270. Alanine scanning of
      this dominant epitope indicated that five amino acids, Y260, D261, D262, K264 and
      D266, contribute most towards IgE-binding. A model based on the structure of the
      beta subunit of soybean beta-conglycinin revealed that Gly m Bd 28 K contains two
      cupin domains. The dominant epitope is on the edge of the first beta-sheet of the
      C-terminal cupin domain and is present on a potentially solvent-accessible loop
      connecting the two cupin domains. Thus, the C-terminal 23 kDa polypeptide of Gly
      m Bd 28 K present in soy products is allergenic and apparently contains at least
      one immunodominant epitope near the edge of a cupin domain. This knowledge could
      be helpful in the future breeding of hypoallergenic soybeans.

PMID- 15252734
TI  - The growth of soybean under free air [CO(2)] enrichment (FACE) stimulates
      photosynthesis while decreasing in vivo Rubisco capacity.
AB  - Down-regulation of light-saturated photosynthesis (A(sat)) at elevated
      atmospheric CO(2) concentration, [CO(2)], has been demonstrated for many C(3)
      species and is often associated with inability to utilize additional
      photosynthate and/or nitrogen limitation. In soybean, a nitrogen-fixing species,
      both limitations are less likely than in crops lacking an N-fixing symbiont.
      Prior studies have used controlled environment or field enclosures where the
      artificial environment can modify responses to [CO(2)]. A soybean free air
      [CO(2)] enrichment (FACE) facility has provided the first opportunity to analyze
      the effects of elevated [CO(2)] on photosynthesis under fully open-air
      conditions. Potential ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      carboxylation (V(c,max)) and electron transport through photosystem II (J(max))
      were determined from the responses of A(sat) to intercellular [CO(2)] (C(i))
      throughout two growing seasons. Mesophyll conductance to CO(2) (g(m)) was
      determined from the responses of A(sat) and whole chain electron transport (J) to
      light. Elevated [CO(2)] increased A(sat) by 15-20% even though there was a small,
      statistically significant, decrease in V(c,max). This differs from previous
      studies in that V(c,max)/J(max) decreased, inferring a shift in resource
      investment away from Rubisco. This raised the C(i) at which the transition from
      Rubisco-limited to ribulose-1,5-bisphosphate regeneration-limited photosynthesis
      occurred. The decrease in V(c,max) was not the result of a change in g(m), which
      was unchanged by elevated [CO(2)]. This first analysis of limitations to soybean
      photosynthesis under fully open-air conditions reveals important differences to
      prior studies that have used enclosures to elevate [CO(2)], most significantly a
      smaller response of A(sat) and an apparent shift in resources away from Rubisco
      relative to capacity for electron transport.

PMID- 15252735
TI  - The DNA-binding protease, CND41, and the degradation of ribulose-1,5-bisphosphate
      carboxylase/oxygenase in senescent leaves of tobacco.
AB  - Plastids bear their own genome, organized into DNA-protein complexes (nucleoids).
      Recently, we identified a DNA-binding protease (CND41) in the chloroplast
      nucleoids of cultured tobacco (Nicotiana tabacum L.) cells. In this study, we
      examine the biochemical function of this novel DNA-binding protease, particularly
      in senescent leaves, because antisense tobacco with a reduced amount of CND41
      showed retarded senescence. Nitrogen-depletion experiments clearly showed that
      CND41 antisense tobacco maintained green leaves and constant protein levels,
      especially ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), throughout
      the whole plant, whereas wild-type tobacco showed marked senescence and the
      reduction of protein levels in the lower leaves. In vitro analyses confirmed that
      CND41 showed proteolytic activity at physiological pH when denatured Rubisco was
      used as the substrate. These results suggest that CND41 is involved in Rubisco
      degradation and the translocation of nitrogen during senescence. The possible
      regulation of protease activity of CND41 through DNA-binding is discussed.

PMID- 15252736
TI  - Survival after oesophagectomy for cancer of the oesophagus.
AB  - BACKGROUND: Formerly an inevitably fatal disease, oesophageal cancer today has
      predictable chances for cure. METHODS: The recent literature and authors' own
      experiences in the surgical management of oesophageal cancer was reviewed to
      identify factors associated with improved survival after oesophagectomy. RESULTS:
      Currently reported overall 5-year-survival rates are reaching 40% and more in
      patients who have had an oesophagectomy performed with curative intention. The
      reasons for improved survival after surgical resection are multifactorial in
      nature: decreased postoperative mortality and morbidity (due to improved patient
      selection, surgical technique and perioperative management), the use of tailored
      surgical strategies (adopted to the histological tumour type, tumour location,
      stage of disease and the individual patient's risk profile), and multimodality
      treatment in patients with locally advanced disease. CONCLUSION: The prognosis of
      patients who have had oesophagectomy for oesophageal cancer has markedly improved
      during the past decades. With improved long-term survival after oesophagectomy,
      postoperative quality of life gains importance as an additional parameter of
      outcome after oesophageal cancer surgery.

PMID- 15252737
TI  - [Cardiac arrhythmias and sudden cardiac death in women].
AB  - BACKGROUND: Gender specific cardiac arrhythmias have been recognized for more
      than 80 years. The impact of gonadal steroids on the autonomic system and on the
      cellular electrophysiology of the cardiac autonomic system are discussed as is a
      direct genetic disposition on a cellular, functional or metabolic level. We
      nevertheless have to be aware of age- and gender-specific differences of heart
      diseases, which have an impact on the incidence, form and severity of cardiac
      arrhythmias. CARDIAC ARRHYTHMIAS IN WOMEN: Gender-specific electrophysiologic
      differences like a higher basic heart rate and a longer QT-interval, beginning
      after puberty, are the main changes in ECGs in women and have a strong
      relationship to constitutional and hormonal influences. Supraventricular
      arrhythmias, i. e. in women sinus and AV-nodal-reentry tachycardias, less
      frequently Wolff-Parkinson-White tachycardias, may show clearly cyclical
      differences. Atrial fibrillation is more frequent in women, is more symptomatic,
      and there are more problems in therapy. Ventricular arrhythmias, occurring
      equally in healthy persons, show a strong relationship to coronary artery disease
      in men, which is less significant in women (in women more arrhythmogenic co
      factors). Women suffer from acquired and congenital long-QT syndrome, and
      consequently more often from torsade-de-pointes tachycardias (stronger drug
      induced QT-lengthening, more short-long sequences, differences in Ikr
      sensitivity). Sudden cardiac death is three times more often in men. Women suffer
      from it about ten years later; it is a more heterogenous phenomenon than in men,
      and the prognosis is worse. Women are underrepresented in controlled studies for
      primary and secondary prevention compared to men. CONCLUSIONS: As the underlying
      reasons of gender-specific differences in cardiac arrhythmias are not known in
      detail, the findings discussed imply the necessity of more basic studies to
      evaluate gender-specific solutions for risk stratification and therapy.

PMID- 15252738
TI  - Clinical use and rational management of homocysteine, folic acid, and B vitamins
      in cardiovascular and thrombotic diseases.
AB  - About half of all deaths are due to cardiovascular disease and its complications.
      The economic burden on society and the healthcare system from cardiovascular
      disability, complications, and treatments is huge and becoming larger in the
      rapidly aging populations of developed countries. As conventional risk factors
      fail to account for part of the cases, homocysteine, a "new" risk factor, is
      being viewed with mounting interest. Homocysteine is a sulfur-containing
      intermediate product in the normal metabolism of methionine, an essential amino
      acid. Folic acid, vitamin B(12), and vitamin B(6) deficiency and reduced enzyme
      activities inhibit the breakdown of homocysteine, thus increasing the
      intracellular homocysteine concentration. Numerous retrospective and prospective
      studies have consistently found an independent relationship between mild
      hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting
      at a plasma homocysteine concentration of approximately 10 micromol/l, the risk
      increase follows a linear dose-response relationship with no specific threshold
      level. Hyperhomocysteinemia as an independent risk factor for cardiovascular
      disease is thought to be responsible for about 10 percent of total risk. Elevated
      plasma homocysteine levels (> 12 micromol/l; moderate hyperhomocysteinemia) are
      considered cytotoxic and are found in 5 to 10 percent of the general population
      and in up to 40 percent of patients with vascular disease. Additional risk
      factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may
      additively or, by interacting with homocysteine, synergistically (and hence
      overproportionally) increase overall risk. Hyperhomocysteinemia is associated
      with alterations in vascular morphology, loss of endothelial antithrombotic
      function, and induction of a procoagulant environment. Most known forms of damage
      or injury are due to homocysteine-mediated oxidative stresses. Especially when
      acting as direct or indirect antagonists of cofactors and enzyme activities,
      numerous agents, drugs, diseases, and life style factors have an impact on
      homocysteine metabolism. Folic acid deficiency is considered the most common
      cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of
      folate per day is difficult to maintain even with a balanced diet, and high-risk
      groups often find it impossible to meet these folate requirements. Based on the
      available evidence, there is an increasing call for the diagnosis and treatment
      of elevated homocysteine levels in high-risk individuals in general and patients
      with manifest vascular disease in particular. Subjects of both populations should
      first have a baseline homocysteine assay. Except where manifestations are already
      present, intervention, if any, should be guided by the severity of
      hyperhomocysteinemia. Consistent with other working parties and consensus groups,
      we recommend a target plasma homocysteine level of < 10 micromol/l. Based on
      various calculation models, reduction of elevated plasma homocysteine
      concentrations may theoretically prevent up to 25 percent of cardiovascular
      events. Supplementation is inexpensive, potentially effective, and devoid of
      adverse effects and, therefore, has an exceptionally favorable benefit/risk
      ratio. The results of ongoing randomized controlled intervention trials must be
      available before screening for and treatment of hyperhomocysteinemia can be
      recommended for the apparently healthy general population.

PMID- 15252739
TI  - [Cardiac efficiency in patients with Cheyne-Stokes respiration as a result of
      heart insufficiency during long-term nasal respiratory treatment with adaptive
      servo ventilation (AutoSet CS)].
AB  - Cheyne-Stokes respiration (CSR) is known to be an important negative predictor of
      outcome in patients with congestive heart failure. The goal of this study was to
      investigate whether the use of adaptive servo ventilation (AutoSet CS) would
      permit sufficient suppression of this pathological breathing pattern and improve
      cardiac function in longterm use over 1 year. Inclusion criteria for the study
      were congestive heart failure (left ventricular ejection fraction 20-50%), proven
      CSR with a central apnea-hypopnea index (AHI) > 15/h and stable clinical status
      with standard medical therapy. Patients with obstructive sleep apnea and COPD
      were excluded. Twenty consecutive patients (16 male) age 65.5 years (range 48-77)
      were followed with full blood counts, blood gas analysis, lung function tests and
      questionnaires for cardiopulmonary capacities (Minnesota, MRC Scale) and
      sleepiness (Epworth Sleepiness Scale). In addition, we performed 6-min walk
      distance (6MWD), echocardiography and polysomnography just before and after
      adjusting to adaptive servo ventilation and 3 and 12 months later. Mean usage of
      adaptive servo ventilation was sufficient (4.3 +/- 2.1 h/day at 12 months). No
      significant changes in blood gas analysis, blood counts and pulmonary function
      were detectable. CSR disappeared almost completely in all patients (AHI pre-study
      44.3 +/- 13.4/h vs 3.4 +/- 8.0/h at 12 months; p < 0.0001). Saturation normalized
      steadily over the course of the study. The desaturation index decreased from 45.3
      +/- 17.8/h to 5.2 +/- 11.5/h at 12 months (p < 0.0001). Mean saturation increased
      with the first night of sleep with adaptive servo ventilation from 92.0 +/- 2.5%
      to 93.0 +/- 1.6% (p < 0.05) and then to 94.1 +/- 1.9% at 3, and 94.2 +/- 1.9% at
      12 months (p < 0.001). Quality of sleep was significantly improved with an
      increase of slow-wave sleep from 4.5 +/- 4.6% to 13.7 +/- 6.9% at 12 months (p <
      0.0001). The arousal index concomitantly decreased from 29.8 +/- 17.9/h pre-study
      to 12.0 +/- 10.3/h at 12 months (p < 0.01). REM-sleep and sleep efficiency
      remained unchanged. The Epworth Sleepiness Scale showed only a trend to
      improvement. Cardiac function improved significantly during the course of the
      study. The ejection fraction increased from mean 37.1 +/- 12.5% pre-study to 41.7
      +/- 8.8% at 12 months (p < 0.05). The 6-min walk distance increased from 192 +/-
      110 m to 277 +/- 130 m at 12 months (p < 0.01). The MRC and Minnesota score were
      not significantly different pre- and post-study. We conclude that long-term
      respirator therapy with adaptive servo ventilation has sufficiently suppressed
      CSR and improved cardiac function in patients with congestive heart failure.
      Thus, safety and feasibility of this respirator therapy could be demonstrated.
      However, due to methodological reasons (no control group, no randomization) a
      direct effect on cardiac function could not be confirmed.

PMID- 15252740
TI  - Identification and ablation of atypical atrial flutter. Entrainment pacing
      combined with electroanatomic mapping.
AB  - Differentiation between typical and atypical atrial flutter solely based upon
      surface ECG pattern may be limited. However, successful ablation of atrial
      flutter depends on the exact identification of the responsible re-entrant circuit
      and its critical isthmus. Between August 2001 and June 2003, we performed
      conventional entrainment pacing within the cavotricuspid isthmus in 71 patients
      with sustained atrial flutter. In patients with positive entrainment we
      considered the arrhythmia as typical flutter and treated them with conventional
      ablation of the cavotricuspid isthmus. As a consequence of negative entrainment
      we performed 3D-electroanatomic activation mapping (CARTO trade mark ).
      Conventional ablation of the right atrial isthmus was successful in all patients
      (n = 54) with positive entrainment. We performed electroanatomic mapping in the
      remaining 17 patients (14 male; age 60.9 +/- 16 years) resulting in the
      identification of 6 cases with typical and 11 cases with atypical flutter.
      Therefore, entrainment pacing was able to predict the true presence of typical
      atrial flutter in 91.5%. Atypical flutter was right sided in 4 patients and left
      sided in 7 cases. Electrically silent ("low voltage") areas probably
      demonstrating atrial myopathy were identified in all cases with left sided and in
      2 patients with right sided flutter. In these patients targets for ablation lines
      were located between silent areas and anatomic barriers (inferior pulmonary
      veins, mitral respectively tricuspid annulus, or vena cava inferior). In 1
      patient, the investigation was stopped due to variable ECG pattern and atrial
      cycle lengths. In the remaining cases, ablation was acutely successful. One
      patient, after surgical closure of a ventricular septal defect, demonstrated a
      dual-loop intra-atrial reentry tachycardia dependent on two different isthmuses.
      This arrhythmia required ablation of those distinct isthmuses to be interrupted.
      After a mean follow-up of 8.8 +/- 3.4 months, there was one patient with a
      recurrence of left-sided atrial flutter. Another patient developed permanent
      atrial fibrillation shortly after the procedure. Mean duration time of the
      procedure was 235.6 +/- 56.4 min (right atrium: 196 +/- 17.3 min; left atrium:
      267.2 +/- 59.5 min), and average fluoroscopy time was 21.8 +/- 11.7 min (right
      atrium: 9.5 +/- 6 min; left atrium: 28.9 +/- 7 min). There was no incidence of
      serious complications associated with these procedures. In conclusion,
      conventional pacing in the cavotricuspid isthmus combined with electroanatomic
      mapping was an effective method to differentiate between typical and atypical
      atrial flutter. Electroanatomic mapping was a powerful tool both for
      identification of different atrial re-entrant circuits including their critical
      isthmuses as well as for effective application of individual ablation line
      strategies.

PMID- 15252741
TI  - [The prediction of atrial fibrillation recurrence after electrical cardioversion
      with P wave signal averaged EKG].
AB  - METHOD: A P wave triggered and bidirectional P wave signal averaged ECG was used
      among 49 patients (35 m/14 w) 24 hours after electrical cardioversion. The
      measurements were only managed in sinus rhythm. Each patient was followed up for
      at least 6 months and the mean follow-up was of 9.1 months. RESULTS: A recurrence
      of atrial fibrillation was observed in 23 patients (47%) after a mean of 9,2 days
      (range 2-92 days). There was no difference in organic heart disease or in the use
      of drugs. The filtered P wave duration (FPD) was longer significantly (136.2 +/-
      20.1 vs 119.5 +/- 19.8 ms, p < 0.0001) and the root mean square voltage of the
      last 20 ms of the P wave (RMS 20) was lower (2.77 +/- 1.10 vs 4.17 +/- 1.43
      microV, p < 0.0001) in patients with a recurrence of atrial fibrillation. A cut
      off point (COP) of FPD > or = 126 ms and RMS 20 < or = 3.1 microV achieved a
      specificity of 69%, a sensitivity of 74%, a positive predictive value of 68% and
      a negative predictive value of 75%. CONCLUSION: The results of our study suggest
      that the recurrence of atrial fibrillation after electrical cardioversion can be
      detected by P wave signal averaged ECG. The occurrence of COP seems to be a high
      risk factor of the recurrence of atrial fibrillation. The predictive power of the
      method has to be examined by prospective investigations of a larger patient
      population and a longer follow-up. The recurrence of atrial fibrillation after
      cardioversion has a high incidence. In our study, P wave signal averaged ECG was
      performed one day after successful electrical cardioversion in order to evaluate
      the utility of this method to predict atrial fibrillation after cardioversion.

PMID- 15252742
TI  - [Treatment of recurrent neurocardiogenic syncope with cardiac inhibitors with
      ipratropium bromide].
AB  - Pharmacological approaches for the treatment of cardioinhibitory vasovagal
      syncope are controversially discussed in the literature. In acute treatment of
      neurocardiogenic syncope, anticholinergics (atropine) are used effectively.
      Randomised and placebo-controlled clinical trials evaluating the preventive
      significance of anticholinergic agents in the therapy of cardioinhibitory
      vasovagal syncope are still missing. We report the case of an 18-year-old male
      patient with recurrent convulsive, cardioinhibitory neurocardiogenic syncope.
      Vasovagal syncope occurred predominantly as centrally induced syncope triggered
      by negative emotions such as fear or by seeing blood. Under resting conditions,
      the patient revealed increased parasympathetic tone with nocturnal bradycardia of
      38 beats/min. In the course of head-up tilt table testing a cardioinhibitory
      syncope with an asystolic pause of 10 seconds occurred without any prodromes
      after 10 minutes of upright positioning. In order to inhibit parasympathetic
      tone, medication with ipratropiumbromide was initiated. Time-variant analysis of
      heart rate variability (autoregressive model) during head-up tilt table testing
      showed under the medication with ipratropiumbromide a vagal mediated
      cardioinhibition to 56 beats/min, but no further sinus arrest. Throughout
      clinical follow-up of 6 months the patient remained syncope-free under the
      medication. The usefulness of ipratropiumbromide in inhibiting vagal mediated
      cardioinhibition will be discussed referring to the case report and to studies
      evaluating anticholinergic agents in the treatment of neurocardiogenic syncope.

PMID- 15252743
TI  - Cardiogenic shock due to thrombotic thrombocytopenic purpura.
AB  - We report the case of a 49-year-old man with thrombotic thrombocytopenic purpura
      (TTP) leading to cardiogenic shock. Laboratory data were typical for TTP with
      thrombocytopenia and microangiopathic hemolytic anemia. The electrocardiogram
      recorded significant ST-segment elevations in the anterior and inferior leads. In
      addition' coronary angiography showed normal epicardial coronary arteries with
      slow flow. The patient died due to electromechanical dissociation six hours after
      admission. During autopsy typical features of thrombotic thrombocytopenic purpura
      were found. Histological preparation of the heart showed a diffuse myocardial
      necrosis due to microvascular thrombosis. Cardiac involvement is common in TTP
      but extended myocardial necrosis has been reported in only a few cases.

PMID- 15252744
TI  - Endocardial radiofrequency ablation of septal hypertrophy. A new catheter-based
      modality of gradient reduction in hypertrophic obstructive cardiomyopathy.
AB  - Transcoronary alcohol ablation of septal hypertrophy (TASH) is a therapeutic
      catheter based option and an alternative to surgery in the treatment of patients
      with hypertrophic obstructive cardiomyopathy. However, the anatomic variability
      of the vascularisation of the obstructing septal bulge may limit the therapeutic
      efficacy. Thus, we examined an endocardial approach as an alternative. Based on
      the effects of radiofrequency energy in the treatment of cardiac arrhythmias this
      is the first report about the use of this modality. It refers to a 45-year-old
      patient with severe HOCM. The energy was applied by using a cooled-tip ablation
      catheter at the right side of the ventricular septum. The site corresponded to
      the obstructing area of the left ventricle. The following changes could be
      observed: a reduction of the intraventricular pressure gradient during the
      therapeutic session, a gradient reduction at cycle exercise as assessed by
      Doppler echocardiography 7 days after intervention, a subaortic septal
      hypokinesia, an enlargement of the left ventricular outflow tract, a reduction of
      the septal thickness and an increase in the exercise capacity using the 6-minute
      walk test. These changes are in accordance with the results after TASH and
      surgical treatment. The new modality might extend the possibilities in the
      catheter-based treatment of patients with severe HOCM.

PMID- 15252746
TI  - Water exchange between the pregnant ewe, the foetus and its amniotic and
      allantoic fluids.
AB  - Water exchange between the ewe and its foetus was measured in two Merino ewes
      maintained with continuous feeding under thermoneutral conditions from about day
      90 of gestation to term. Catheters were established in the maternal pulmonary
      artery (MPA), the foetal dorsal aorta (FDA) and the amniotic and allantoic sacs.
      Doses of tritiated water were given into either the MPA or the FDA on five
      occasions, three for one ewe and two for the other, at least 6 days apart and
      samples were taken from all catheters for 31 h following the dose. An open, eight
      compartment restricted model was developed which simultaneously fitted the tracer
      data and the ewes' water balance, determined by measurement and calculation. The
      ewes delivered live lambs at term. Water was exchanged between ewe and foetus at
      16-43 l h(-1) whereas net flow to the foetus averaged 82 ml day(-1). Turnover
      times were 20-39 min in the ewes' body water, 2-7 min in foetal body water, 10-58
      min in amniotic water and 3-22 min in allantoic water; the whole-body half-times
      were 4.5-5.7 days. The data suggest that intramembranous exchange was the major
      contributor to water exchange in amniotic and allantoic fluids. The mean
      residence time of water in the rumen (39-52 min) was shorter than in non-pregnant
      sheep, suggesting that blood flow to the rumen increased during mid to late
      gestation.

PMID- 15252747
TI  - [Transient visual decrease after photodynamic therapy].
AB  - BACKGROUND: After photodynamic therapy (PDT) some patients complain about a
      transient decrease of visual acuity during the first postoperative week. PATIENTS
      AND METHODS: Prior to and at 2 days and 1 week after PDT the following parameters
      were measured: (1) best corrected visual acuity (VA), (2) changes in refraction,
      and (3) A scan ultrasound biometry was carried out. Linear and 3-D optical
      coherence tomography was performed in three cases. A total of 53 PDT treatments
      were followed-up in 24 patients. RESULTS: Comparison of the pre- and
      postoperative refraction demonstrated a mean hyperopic shift of +0.35 diopters
      (dpt) in 43% of treatments (23/53) on the second postoperative day. The hyperopic
      shift reduced to +0.07 dpt after 1 week. The best corrected VA remained stable or
      was even better in 68% (36/53) on the second postoperative day. A decrease in VA
      could be noticed in 32% (17/53) at this time which declined to 23% (12/53) after
      1 week. Measurement of the cornea-retina distance using A-scan ultrasound
      biometry disclosed a mean axial reduction of 0,13 mm at the second postoperative
      day. This correlates closely with an average hyperopic shift of 0,35 dpt. OCT
      examination disclosed a transient macular edema in the treated retinal areas.
      CONCLUSIONS: A transient hyperopic shift can be measured in 43% on the second
      postoperative day. The subjective decrease in visual acuity measured over the
      postoperative days was mainly due to a transient hyperopic shift in our patients.
      OCT findings disclosed a transient macular edema of the retina treated with PDT,
      which may relate to a hyperopic shift.

PMID- 15252748
TI  - Magnetic resonance image registration and subtraction in the assessment of minor
      changes in low grade glioma volume.
AB  - The purpose of this study was to apply image registration and subtraction to
      standard T2-weighted (T2-W) and FLAIR magnetic resonance imaging (MRI) protocols
      in an attempt to improve the detection of minor changes in low grade glioma
      volume. Thirteen patients with low grade glial tumours and minimal or no apparent
      change on serial MRI scans were prospectively recruited for the study. Forty-two
      pairs of images were compared (T2-W sequences in 27/27 and FLAIR sequences in
      15/27). The image pairs were registered, subtracted and randomised. Three
      independent raters assigned non-parametric ratings according to the dominant
      volume change for unregistered, registered and subtracted image sets. There was a
      statistically significant improvement in the detection of tumour volume change
      using T2-W registration and T2-W and FLAIR registration/subtraction relative to
      unregistered images. The reproducibility and increased sensitivity of FLAIR
      images relative to T2-W images were most apparent when registration was applied.
      Smaller degrees of low grade glioma tumour volume change are detectable using
      image registration and subtraction techniques that can be applied successfully to
      images acquired with standard clinical protocols.

PMID- 15252749
TI  - Acute hydrocarbon pneumonia after white spirit aspiration: sequential HRCT
      findings.
AB  - Hydrocarbon pneumonia is a very uncommon condition resulting from aspiration of
      mineral oil into the lung. We report the first description of early and
      sequential high-resolution computed tomographic (HRCT) findings of hydrocarbon
      pneumonia following attempted suicide by white spirit aspiration. Initial HRCT
      showed patchy opacities of coalescing masses with well-defined walls. They were
      visible in the middle lobe, lingula and lower lobes. Follow-up CT showed
      regression of the alveolar opacities, the presence of pneumatoceles and right
      asymptomatic pneumothorax. After 23 months of follow-up, the patient remained
      asymptomatic, and the follow-up CT scan was considered normal. The radiological
      features and a review of the relevant literature are briefly discussed.

PMID- 15252750
TI  - [Criticizing posttraumatic stress disorder].

PMID- 15252751
TI  - [The impact of Alzheimer's disease on the pain processing].
AB  - It is well known that patients with Alzheimer's disease report less pain in
      comparison to their age group. However, little is yet known about the underlying
      mechanisms causing the decreased pain report. In order to learn more about these
      mechanisms, experimental studies are indispensable, since only in experimental
      settings, noxious input and pain experience can be assessed independently. We
      therefore report on experimental data on pain perception in Alzheimer's disease
      in this review. The experimental data suggest that the threshold for pain
      tolerance is markedly increased and the autonomic pain reaction is, at least in
      part, considerably diminished. On the other hand, pain threshold and pain event
      related brain potentials remain largely unchanged. As possible explanations we
      discuss age-related changes in pain perception and neuroanatomical changes in
      Alzheimer's disease. Particularly the atrophy of limbic structures may have a
      modifying impact on the pain experience. We also discuss what influence
      communicational deficits have on pain report.

PMID- 15252752
TI  - [Semantic dementia: clinical profile and cognitive-neuropsychological relevance].
AB  - Semantic Dementia (SD) represents a rare variant of presenile primary
      degenerative diseases of "frontotemporal lobar degenerations" (FTLD). SD is
      characterized by anterior-temporal atrophy and a selective semantic deficit.
      Neuropsychological impairment either bears on fluent aphasia with marked naming
      and comprehension difficulties or on a disorder of object recognition or on both.
      Behavioural alterations such as stereotyped behaviour and change in food
      preference become prominent as the disease progresses and are interpreted as a
      correlative for the pathological spreading to frontal structures. Since SD is
      often misclassified as Alzheimer's disease (AD), but calls for a different
      management, diagnostic consensus criteria by Neary and colleagues are depicted.
      The neuropsychological profile is described in detail and complemented by a case
      report. Implications from the dissociation of disturbed memory systems of SD
      (semantic) and AD (episodic) for models of long-term memory are discussed in
      terms of connectivity in the medial temporal lobe. SD can contribute to a better
      understanding of the structure and organisation of the semantic system.

PMID- 15252753
TI  - [Quality of life and therapeutic result in outpatients with schizophrenia under
      flupenthixol treatment].
AB  - The objective of this phase IV surveillance study was to document the efficacy
      and tolerability of flupenthixol as well as the quality of life of patients
      suffering from schizophrenia and to gain insights into which doses were actually
      used in specialists outpatients care. The observational variables in this study
      include demographic variables, details of the diagnosis as well as concomitant
      diseases. Further evaluations included the assessment of CGI-Scale and subjective
      patient quality of live assessment using a standardised questionnaire. This
      questionnaire SWN-K (subjective well-being under neuroleptic treatment; short
      version) includes 20 items on the state of health with a six-point scale from
      "absolutely not" to "very strong" respectively. 66.3 % Patients were treated with
      the depot form of flupenthixol, the rest with oral medication with mean doses of
      9.2 mg/d i. m. and 6.3 mg/d p. o. respectively. 78.8 % of patients improved on
      the CGI-Scale, 5.5 % had an adverse event and in 4.6 % of patients this event was
      related to the medication. 0.3 % of patients had a serious adverse event. The
      mean of SWN-K improved from 61.2 to 78.5 in the course of study. The CGI improved
      from 5.83 to 3.43 in the course of treatment.

PMID- 15252754
TI  - [The "AMDP scale for dissociation and conversion (AMDP-DK)": development of an
      observer-rated scale and first psychometric properties].
AB  - The AMDP scale for dissociation and conversion (AMDP-DK) represents an observer
      rated scale for the assessment of dissociative and conversive phenomena, which
      closes the gap between available self-report questionnaires and time-consuming
      structured interviews with their respective disadvantages. The instrument
      comprises 30 operationalized items, which are rated according to the AMDP rules,
      and which are theoretically-driven divided into the subscales dissociation (15
      items), conversion (9 items) and a "formal" dimension (6 items) to cover
      associated phenomena. In a sample of psychiatric inpatients (n = 73) the covered
      symptoms showed a great variety of frequency and intensity. The AMDP-DK and its
      subscales had good internal consistency (Cronbachs alpha between 0.76 and 0.85).
      A factor-analysis mostly replicated the theoretically constructed subscales. The
      convergent and divergent validity of the scale was good, as well as its ability
      to discriminate between high- and low-dissociating patients. The findings are
      discussed with regard to the psychometric properties and the relevance for the
      theories of dissociation and conversion.

PMID- 15252755
TI  - [Acute and chronic posttraumatic stress disorder].

PMID- 15252756
TI  - Microarray analysis of cell-free fetal DNA in amniotic fluid: a prenatal
      molecular karyotype.
AB  - Metaphase karyotype analysis of fetal cells obtained by amniocentesis or
      chorionic villus sampling is the current standard for prenatal cytogenetic
      diagnosis, particularly for the detection of trisomy 21. We previously
      demonstrated that large quantities of cell-free fetal DNA (cffDNA) are easily
      extracted from amniotic fluid (AF). In this study, we explored potential clinical
      applications of AF cffDNA by testing its ability to hybridize to DNA microarrays
      for comparative genomic hybridization (CGH) analysis. cffDNA isolated from 11
      male fetuses showed significantly increased hybridization signals on SRY and
      decreased signals on X-chromosome markers, compared with female reference DNA.
      cffDNA isolated from six female fetuses showed the reverse when compared with
      male reference DNA. cffDNA from three fetuses with trisomy 21 had increased
      hybridization signals on the majority of the chromosome 21 markers, and cffDNA
      from a fetus with monosomy X (Turner syndrome) had decreased hybridization
      signals on most X-chromosome markers, compared with euploid female reference DNA.
      These results indicate that cffDNA extracted from AF can be analyzed using CGH
      microarrays to correctly identify fetal sex and aneuploidy. This technology
      facilitates rapid screening of samples for whole-chromosome changes and may
      augment standard karyotyping techniques by providing additional molecular
      information.

PMID- 15252757
TI  - Genomewide scan for gout in taiwanese aborigines reveals linkage to chromosome
      4q25.
AB  - Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population,
      including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia
      and gout, which suggests a founder effect across the Pacific region. We report
      here a genomewide linkage study of 21 multiplex pedigrees with gout from an
      aboriginal tribe in Taiwan. From observations of familial clustering, early onset
      of gout, and clinically severe manifestations, we hypothesized that a major gene
      plays a role in this trait. Using 382 random polymorphic markers spread across 22
      autosomes, we demonstrated a highly significant linkage for gout at marker
      D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all)
      statistic]; empirical P=.0006; LOD=4.3, P=4.4x10-6 by logistic regression). When
      alcohol consumption was included as a covariate in the model, the LOD score
      increased to 5.66 (P=1.3x10-6). Quantitative traits, including serum uric acid
      and creatinine, also showed a moderate linkage to this region. To our knowledge,
      this is the first genome-scan report to identify a genetic locus harboring a gout
      susceptibility gene.

PMID- 15252760
TI  - Epidemiology of acute deep vein thrombosis.
AB  - Although the factors leading to venous thrombosis have been known for over a
      century, Virchow's initial model of thrombosis has been extensively refined.
      Activated coagulation is now recognized to be of primary importance in venous
      thrombogenesis; the concept of venous injury has been expanded to include
      molecular changes in the endothelium; and stasis has been redefined as a largely
      permissive factor. Furthermore, it is now clear that venous thrombi undergo a
      dynamic evolution beginning early after their formation. The natural history of
      acute deep venous thrombosis (DVT) is a balance between recurrent thrombotic
      events and processes that restore the venous lumen, both of which have important
      implications for the development of complications. Although pulmonary embolism
      (PE) is clearly the most life threatening complication of acute DVT, the long
      term socio-economic consequences of the post thrombotic syndrome (PTS) have
      perhaps been underemphasized in clinical trials. The development of post
      thrombotic manifestations is related to both residual venous obstruction and
      valvular incompetence. Recognition of the factors contributing to a poor outcome,
      including recurrent thrombotic events, the rate of recanalization, the global
      extent of venous reflux, and the anatomic distribution of reflux and obstruction
      is important, as there may be therapeutic alternatives to alter the natural
      history of acute DVT. The treatment alternatives will continue to expand with the
      introduction of new therapeutic drugs, for both systemic and catheter-directed
      therapy, and mechanical thrombectomy devices. The primary care physician is
      challenged with the task of correctly evaluating deep vein thrombosis and
      providing his patient with access to the most clinically appropriate, and cost
      effective, diagnostic and management options available. This article will review
      the epidemiology of DVT, its risk factors and major complications.

PMID- 15252761
TI  - Current DVT imaging.
AB  - Accurate diagnosis of deep venous thrombosis (DVT) is very difficult, and imaging
      plays a crucial role in the diagnosis or exclusion of DVT. The initial test of
      choice for diagnosis of acute thigh as well as upper extremity DVT is ultrasound,
      because of its high accuracy, relatively low cost, portability, and lack of
      ionizing radiation. In patients who are undergoing CT pulmonary angiography for
      suspected pulmonary embolism, CT venography can be performed as part of the
      examination, for comprehensive evaluation of the venous system in the legs,
      abdomen, and pelvis. MR has a problem-solving role, and conventional venography
      is now limited to specific scenarios including evaluation of central DVT in the
      upper extremities, as a prelude to intervention for thrombolysis/thrombectomy,
      and prior to placement of an inferior vena cava filter. This article discusses
      the imaging findings of DVT, and the role of these imaging examinations in the
      evaluation of patients with suspected DVT.

PMID- 15252758
TI  - Signatures of selection and gene conversion associated with human color vision
      variation.
AB  - Trichromatic color vision in humans results from the combination of red, green,
      and blue photopigment opsins. Although color vision genes have been the targets
      of active molecular and psychophysical research on color vision abnormalities,
      little is known about patterns of normal genetic variation in these genes among
      global human populations. The current study presents nucleotide sequence analyses
      and tests of neutrality for a 5.5-kb region of the X-linked long-wave "red" opsin
      gene (OPN1LW) in 236 individuals from ethnically diverse human populations. Our
      analysis of the recombination landscape across OPN1LW reveals an unusual
      haplotype structure associated with amino acid replacement variation in exon 3
      that is consistent with gene conversion. Compared with the absence of OPN1LW
      amino acid replacement fixation since divergence from chimpanzee, the human
      population exhibits a significant excess of high-frequency OPN1LW replacements.
      Our results suggest that subtle changes in L-cone opsin wavelength absorption may
      have been adaptive during human evolution.

PMID- 15252762
TI  - Medical management of venous thromboembolic disease.
AB  - Venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) are
      common disorders with serious morbid and mortal complications. Given the varied
      modes of presentation, a high clinical index of suspicion in patients at risk
      must exist among physicians. Standard therapy has consisted of intravenous
      unfractionated heparin and overlapping administration of an oral Vitamin K
      antagonist, commonly Warfarin. Although an effective strategy, many practical
      limitations exist, including the need for prolonged hospitalization, frequent
      laboratory monitoring for anticoagulant effect, and erratic dose-response curves.
      Recently, subcutaneous low-molecular-weight heparins have emerged as safe and
      effective alternatives for unfractionated heparin. Appropriate patients may be
      treated with low-molecular-weight heparins and oral Warfarin entirely as
      outpatients, with similar efficacy and risk of recurrent thromboembolic events
      and hemorrhage. Thrombolytic therapy is a reasonable alternative in patients with
      iliofemoral venous thrombosis and/or pulmonary embolism resulting in hemodynamic
      compromise or obstructing significant pulmonary vasculature. Risks of serious
      hemorrhagic side effects including intracranial hemorrhage, along with the added
      economic burden, have limited widespread acceptance of thrombolytic therapy as
      primary treatment. Emerging oral direct thrombin inhibitors and other novel
      agents stand to move the treatment of patients with venous thromboemboli to even
      greater levels of safety and efficacy.

PMID- 15252764
TI  - Mechanical thrombectomy for DVT.
AB  - Deep venous thrombosis is a common source of morbidity and mortality in the
      United States. Complications include pulmonary embolism and chronic post
      thrombotic syndrome. Chronic post-thrombotic syndrome is characterized by
      extremity pain, edema, venous claudication, skin changes, and skin ulceration.
      This syndrome is attributed to venous obstruction and valvular damage due to
      thrombus. The standard treatment of deep venous thrombosis consists of medical
      management with anticoagulation. Anticoagulation has proven efficacy in
      prevention of thrombus extension, pulmonary embolus, and re-thrombosis. The role
      of anticoagulation in post-thrombotic syndrome is unclear. Aggressive
      endovascular techniques for managing DVT have evolved as a result. Catheter
      directed thrombolysis was the first such procedure with demonstrated efficacy,
      however its acceptance has been limited by perceived risks, time to lysis, and
      cost. As a result, alternative measures for managing DVT have evolved including
      mechanical thrombectomy. Mechanical thrombectomy for DVT has the potential to
      shorten the time for lysis, reduce the risk of thrombolytic agents, and
      potentially impact cost savings.

PMID- 15252763
TI  - Thrombolysis for lower extremity deep venous thrombosis.
AB  - Catheter-directed thrombolysis (CDT) has been proposed as an alternative mode of
      therapy to anticoagulation in patients with massive, symptomatic deep vein
      thrombosis of the extremity. The major goal of therapy is to rapidly restore
      venous blood flow, reduce the pain and edema of the extremity, preserve venous
      valve function, and reduce chronic symptoms related to chronic venous
      hypertension (postthrombotic syndrome). In patients with iliofemoral deep venous
      thrombosis (DVT) standard angiographic techniques are used to instrument a lower
      extremity vein (popliteal) and venography is performed followed by catheter
      directed infusion of a plasminogen activator directly into the thrombus.
      Following lytic infusion, the interventionalist must evaluate the venous drainage
      to determine if there is an anatomic lesion that requires further endovascular
      treatment (eg, iliac vein compression syndrome). Posttreatment therapy usually
      consists of warfarin therapy and venous compression stockings for at least 3 to 6
      months. The purpose of this article is to review the technical approach used in
      treating iliofemoral DVT and highlight the hurdles that face interventionalists
      in attempting to broaden this procedure to most types of lower extremity DVT.

PMID- 15252765
TI  - Upper extremity deep venous thrombosis: interventional management.
AB  - Upper extremity deep venous thrombosis, previously thought to be a relatively
      innocuous disorder in comparison to lower extremity deep venous thrombosis, has
      recently begun to receive the attention it merits. Its optimal management remains
      controversial despite the development of several new techniques and devices which
      allow more rapid removal of thrombus and treatment of underlying venous stenotic
      disease. The following article provides a framework to discuss its treatment,
      with the emphasis on endovascular management.

PMID- 15252766
TI  - Inferior vena cava filters.

PMID- 15252767
TI  - Retrievable vena cava filters.

PMID- 15252768
TI  - Superior vena cava filters.

PMID- 15252770
TI  - Nitric oxide synthesis in the kidney: isoforms, biosynthesis, and functions in
      health.
AB  - Nitric oxide (NO) is a gaseous free radical that serves cell signaling, cellular
      energetics, host defense, and inflammatory functions in virtually all cells. In
      the kidney and vasculature, NO plays fundamental roles in the control of systemic
      and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure
      natriuresis, release of sympathetic neurotransmitters and renin, and tubular
      solute and water transport. NO is synthesized from L-arginine by NO synthases
      (NOS). Because of its high chemical reactivity and high diffusibility, NO
      production by each of the 3 major NOS isoforms is regulated tightly at multiple
      levels from gene transcription to spatial proximity near intended targets to
      covalent modification and allosteric regulation of the enzyme itself. Many of
      these regulatory mechanisms have yet to be tested in renal cells. The NOS
      isoforms are distributed differentially and regulated in the kidney, and there
      remains some controversy over the specific expression of functional protein for
      the NOS isoforms in specific renal cell populations. Mice with targeted deletion
      of each of the NOS isoforms have been generated, and these each have unique
      phenotypes. Studies of the renal and vascular phenotypes of these mice have
      yielded important insights into certain vascular diseases, ischemic acute renal
      failure, the tubuloglomerular feedback response, and some mechanisms of tubular
      fluid and electrolyte transport, but thus far have been underexploited. This
      review explores the collective knowledge regarding the structure, regulation, and
      function of the NOS isoforms gleaned from various tissues, and highlights the
      progress and gaps in understanding in applying this information to renal and
      vascular physiology.

PMID- 15252771
TI  - NO bioavailability, endothelial dysfunction, and acute renal failure: new
      insights into pathophysiology.
AB  - This brief overview sketches current evidence of imbalance between inducible
      nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), role
      of oxidant stress, and generation of peroxynitrite in the pathophysiology of
      acute ischemic renal injury. The development of endothelial cell dysfunction at
      early stages of experimental acute renal ischemia is the focus of the review,
      with the results of recent studies on amelioration of renal injury by the infused
      endothelial cells engrafting in the renal microcirculation. Finally, this article
      provides some future perspectives on the potential usefulness of endothelial
      progenitor cells in the prevention and treatment of acute renal failure.

PMID- 15252772
TI  - Nitric oxide and glomerulonephritis.
AB  - Glomerulonephritis is a common clinical condition that is caused by immune
      mediated injury to the kidney and is characterized by dysfunction of the
      glomerular capillary filtration barrier. Nitric oxide (NO), a ubiquitous molecule
      with many biological functions throughout the body, has been evaluated as an
      inflammatory mediator in these circumstances. NO may induce glomerular injury
      directly or may act via stimulation of a host of other inflammatory mediators. A
      variety of experimental models of glomerulonephritis have been studied including
      those induced by infusion of antibodies to the Thy1.1 antigen or glomerular
      basement membrane, Heymann nephritis, and autoimmune nephritis. In virtually all
      of these cases there is evidence of increased NO production. Excessive production
      of NO by inducible nitric oxide synthase (iNOS), derived from infiltrating immune
      cells or resident glomerular cells, nearly always is associated with increased
      glomerular injury. Interventions that inhibit this enzyme result in less
      proteinuria and diminished glomerular damage. In contrast, NO derived from
      endothelial nitric oxide synthase (eNOS) may limit glomerular disease by
      preserving endothelial cell integrity. There are only a limited number of studies
      that have evaluated the impact of NO in patients with glomerulonephritis.
      Although the bulk of evidence supports a role of NO as a pro-inflammatory
      mediator in glomerulonephritis, additional work is needed to show an association
      between altered NO production and the severity and outcome of disease in patients
      with this disease. It is hoped that better understanding of the role of NO in
      glomerulonephritis will lead to the development of therapies to ameliorate the
      disease.

PMID- 15252773
TI  - Role of nitric oxide in diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      Western hemisphere. Endothelial dysfunction is the central pathophysiologic
      denominator for all cardiovascular complications of diabetes including
      nephropathy. Abnormalities of nitric oxide (NO) production modulate renal
      structure and function in diabetes but, despite the vast literature, major gaps
      exist in our understanding in this field because the published studies mostly are
      confusing and contradictory. In this review, we attempt to review the existing
      literature, discuss the controversies, and reach some general conclusions as to
      the role of NO production in the diabetic kidney. The complex metabolic milieu in
      diabetes triggers several pathophysiologic mechanisms that simultaneously
      stimulate and suppress NO production. The net effect on renal NO production
      depends on the mechanisms that prevail in a given stage of the disease. Based on
      the current evidence, it is reasonable to conclude that early nephropathy in
      diabetes is associated with increased intrarenal NO production mediated primarily
      by constitutively released NO (endothelial nitric oxide synthase [eNOS] and
      neuronal nitric oxide synthase [nNOS]). The enhanced NO production may contribute
      to hyperfiltration and microalbuminuria that characterizes early diabetic
      nephropathy. On the other hand, a majority of the studies indicate that advanced
      nephropathy leading to severe proteinuria, declining renal function, and
      hypertension is associated with a state of progressive NO deficiency. Several
      factors including hyperglycemia, advanced glycosylation end products, increased
      oxidant stress, as well as activation of protein kinase C and transforming growth
      factor (TGF)-beta contribute to decreased NO production and/or availability.
      These effects are mediated through multiple mechanisms such as glucose quenching,
      and inhibition and/or posttranslational modification of NOS activity of both
      endothelial and inducible isoforms. Finally, genetic polymorphisms of the NOS
      enzyme also may play a role in the NO abnormalities that contribute to the
      development and progression of diabetic nephropathy.

PMID- 15252774
TI  - Nitric oxide and tubulointerstitial nephritides.
AB  - As part of the exponential growth in our understanding of nitric oxide (NO) in
      health and disease over the past 2 decades, the kidney has become appreciated as
      a major site where NO may play a number of important roles. Although earlier work
      on the kidney focused more on effects of NO at the level of larger blood vessels
      and glomeruli, there has been a rapidly growing body of work showing critical
      roles for NO in tubulointerstitial disease. In this review we discuss some of the
      recent contributions to this important field.

PMID- 15252775
TI  - Nitric oxide, oxidative stress, and progression of chronic renal failure.
AB  - Cellular injury or organ dysfunction from oxidative stress occurs when reactive
      oxygen species (ROS) accumulate in excess of the host defense mechanisms. The
      deleterious effect of ROS occurs from 2 principal actions. First, ROS can
      inactivate mitochondrial enzymes, damage DNA, or lead to apoptosis or cellular
      hypertrophy. Second, nitric oxide (NO), which is a principal endothelial-derived
      relaxing factor, reacts with superoxide anion (O2-) to yield peroxynitrite (ONOO
      ), which is a powerful oxidant and nitrosating agent. The inactivation of NO by
      O2- creates NO deficiency. Oxidative stress can promote the production of
      vasoconstrictor molecules and primary salt retention by the kidney. Several
      hypertensive animal models showed increased activity of nicotine adenine
      dinucleotide phosphate (NADPH) oxidase, which is the chief source of O2- in the
      vessel wall and kidneys. NO regulates renal blood flow, tubuloglomerular feedback
      (TGF), and pressure natriuresis. Animal models of NO deficiency develop
      hypertension, proteinuria, and glomerulosclerosis. Evidence is presented that
      chronic renal failure (CRF) is a state of NO deficiency secondary to decreased
      kidney NO production and/or increased bioinactivation of NO by O2-. Patients with
      CRF show decreased endothelium-dependent vasodilatation to acetylcholine, have
      increased markers of oxidative stress, and diminished antioxidant activity.
      Therapy for oxidative stress has focused on antioxidants and agents that modify
      the renin-angiotensin system. The effects of such treatments are more compelling
      in animal models than in human studies.

PMID- 15252776
TI  - Nitric oxide, angiotensin II, and hypertension.
AB  - Although initially adaptive, the changes that accompany hypertension, namely,
      cell growth, endothelial dysfunction, and extracellular matrix deposition,
      eventually can become maladaptive and lead to end-organ disease such as heart
      failure, coronary artery disease, and renal failure. A functional imbalance
      between angiotensin II (Ang II) and nitric oxide (NO) plays an important
      pathogenetic role in hypertensive end-organ injury. NO, an endogenous
      vasodilator, inhibitor of vascular smooth muscle and mesangial cell growth, and
      natriuretic agent, is synthesized in the endothelium by a constitutive NO
      synthase. NO antagonizes the effects of Ang II on vascular tone, cell growth, and
      renal sodium excretion, and also down-regulates the synthesis of angiotensin
      converting enzyme (ACE) and Ang II type 1 receptors. On the other hand, Ang II
      decreases NO bioavailability by promoting oxidative stress. A better
      understanding of the pathophysiologic mechanisms involved in hypertensive end
      organ damage may aid in identifying markers of cardiovascular susceptibility to
      injury and in developing therapeutic interventions. We propose that those
      antihypertensive agents that lower blood pressure and concomitantly restore the
      homeostatic balance of vasoactive agents such as Ang II and NO within the vessel
      wall would be more effective in preventing or arresting end-organ disease.

PMID- 15252777
TI  - The role of nitric oxide in renal transplantation.
AB  - This review discusses the concept that nitric oxide synthase (NOS) may
      orchestrate both the inflammatory response to the renal allograft and anti
      inflammatory defense in the graft itself. NO is produced by endothelial,
      epithelial, as well as inflammatory cells. In the setting of transplantation, the
      endothelium is the first lining to be subjected to the early response to injury.
      In turn, activated endothelial cells facilitate leukocyte recruitment, immune
      mediated injury, and angiogenesis. On activation by inflammatory stimuli,
      endothelial cells up-regulate multiple vasoactive substances, oxygen radicals,
      cytokines, chemokines, and growth factors. Therefore, endothelial integrity,
      especially the expression of protecting vasoactive agents, such as NO, may be a
      key factor in resistance or sensitivity to transplantation-mediated injury. Thus,
      evaluating the mechanisms by which NO is involved in either protecting or
      injuring the transplanted allogeneic kidney is important for our understanding of
      renal allograft rejection. This review focuses on the role of NO in the
      inflammatory endothelial-leukocyte interactions, which are implicated in acute
      and chronic rejection of the transplanted kidney.

PMID- 15252778
TI  - L-arginine as a therapeutic tool in kidney disease.
AB  - Infusion of L-arginine in experimental animals increases renal plasma flow (RPF)
      and glomerular filtration rate (GFR). It is likely that a component of these
      hemodynamic changes are mediated by nitric oxide (NO) as suggested by studies
      with specific antagonists of L-arginine metabolism. L-arginine administration
      ameliorates the infiltration of the renal parenchyma by macrophages in rats with
      obstructive nephropathy or rats with puromycin-induced nephrotic syndrome. L
      arginine administration also blunts the increase in interstitial volume, collagen
      IV, and alpha-smooth muscle actin. Rats with a remnant kidney given 1% L-arginine
      in the drinking water had a greater GFR and RPF. L-arginine administration also
      decreased proteinuria. Diabetic rats given L-arginine had significantly lower
      excretion of protein and cyclic guanosine monophosphate than diabetic rats not
      receiving L-arginine. Despite persistent hyperglycemia, the administration of L
      arginine prevented the development of hyperfiltration and ameliorated proteinuria
      in diabetic rats. In the setting of ischemic acute renal failure, the
      administration of L-arginine had a beneficial effect on GFR and RPF, decreased O2
      production, diminished up-regulation of soluble guanylate cyclase, and prevented
      up-regulation of inducible NO synthase (iNOS). The pharmacokinetics of L-arginine
      indicate that side effects are rare and mostly mild and dose dependent.

PMID- 15252781
TI  - Tetrahedral chalcogenide clusters and open frameworks.
AB  - By integrating porosity with electrical or optical properties, microporous
      chalcogenides may have unique applications. Here we review recent advances and
      discuss concepts in the synthesis and crystal structure of tetrahedral clusters
      and their frameworks. These chalcogenides can be viewed as trivalent metal
      chalcogenides doped with tetra-, di-, or monovalent metal cations. Low-valent
      cations help to increase the cluster size, while high-valent cations have the
      opposite effect.

PMID- 15252782
TI  - Chemical routes for production of transition-metal phosphides on the nanoscale:
      implications for advanced magnetic and catalytic materials.
AB  - Nanoparticulate transition-metal phosphides remain an unexplored, though emerging
      area of interest on the materials landscape, due principally to their promising
      magnetic and catalytic properties. This review describes synthetic strategies for
      the formation of both supported and unsupported transition-metal phosphide
      nanoparticles, provides a summary of their relevant magnetic and catalytic
      properties, and indicates new directions for exploration.

PMID- 15252783
TI  - Organic chlorine as a hydrogen-bridge acceptor: evidence for the existence of
      intramolecular O--H...Cl--C interactions in some gem-alkynols.
AB  - The acceptor capabilities of "organic" halogen, CX (X=F, Cl, Br, I), with respect
      to hydrogen bonding are controversial, and unactivated organic chlorine is
      generally deemed to be a poor acceptor. Hydrogen bridges of the type O--H...Cl--C
      are uncommon and occur mainly in an intramolecular situation when the donor group
      is sterically hindered, so that the formation of intermolecular interactions is
      difficult. In this paper, intramolecular O--H...Cl--C interactions in a series of
      chloro-substituted gem-alkynols are studied. We describe various features of this
      interaction using crystallographic, spectroscopic and computational methods. The
      O--H...Cl--C interaction occurs in five of the six compounds under consideration
      here (CDDA, 14DDDA, 15DDDA, 18DDDA, 15MKA). Solution (1)H NMR spectroscopy shows
      that the interaction is intramolecular and that it is a true hydrogen bond. DFT
      calculations give a stabilisation energy around 4.0 kcal mol(-1). In the crystal
      structures of the compounds studied, the intramolecular O--H...Cl--C interactions
      fit into the overall scheme of cooperative interactions. These structures may be
      derived from that of the unsubstituted compound DDA by means of synthon exchange
      and the O--H...Cl--C interaction fares surprisingly well in the presence of
      competing stronger acceptors. The crystal structures show an unusual degree of
      modularity for compounds that generally form interactions that are weak and
      variable. It is noteworthy that the so-called "weak" acceptor, organic chlorine,
      is able to sustain a good intramolecular hydrogen bridge that is of an attractive
      and stabilizing nature and which is of potential importance in crystal
      engineering and supramolecular chemistry.

PMID- 15252784
TI  - The synthesis and electronic structure of a novel [NiS4Fe2(CO)6] radical cluster:
      implications for the active site of the [NiFe] hydrogenases.
AB  - A novel [NiS4Fe2(CO)6]cluster (1: 'S(4)'=(CH(3)C(6)H(3)S(2))(2)(CH(2))(3)) has
      been synthesised, structurally characterised and has been shown to undergo a
      chemically reversible reduction process at -1.31 V versus Fc(+)/Fc to generate
      the EPR-active monoanion 1(-). Multifrequency Q-, X- and S-band EPR spectra of
      (61)Ni-enriched 1(-) show a well-resolved quartet hyperfine splitting in the low
      field region due to the interaction with a single (61)Ni (I=3/2) nucleus.
      Simulations of the EPR spectra require the introduction of a single angle of non
      coincidence between g(1) and A(1), and g(3) and A(3) to reproduce all of the
      features in the S- and X-band spectra. This behaviour provides a rare example of
      the detection and measurement of non-coincidence effects from frozen-solution EPR
      spectra without the need for single-crystal measurements, and in which the S-band
      experiment is sensitive to the non-coincidence. An analysis of the EPR spectra of
      1(-) reveals a 24 % Ni contribution to the SOMO in 1(-), supporting a
      delocalisation of the spin-density across the NiFe(2) cluster. This observation
      is supported by IR spectroscopic results which show that the CO stretching
      frequencies, nu(CO), shift to lower frequency by about 70 cm(-1) when 1 is
      reduced to 1(-). Density functional calculations provide a framework for the
      interpretation of the spectroscopic properties of 1(-) and suggest that the SOMO
      is delocalised over the whole cluster, but with little S-centre participation.
      This electronic structure contrasts with that of the Ni-A, -B, -C and -L forms of
      [NiFe] hydrogenase in which there is considerable S participation in the SOMO.

PMID- 15252785
TI  - Self-assembly, optical behavior, and permeability of a novel capsule based on an
      azo dye and polyelectrolytes.
AB  - A novel capsule composed of an azo dye, Congo red (CR), and different polymers,
      including poly(styrenesulfonate, sodium salt) (PSS), poly(allylamine
      hydrochloride) (PAH), and poly(diallyldimethylammonium chloride) (PDDA), have
      been successfully fabricated by the layer-by-layer self-assembly technique. The
      stepwise linear deposition process was monitored by means of UV-visible
      absorption measurements. The formation of hollow capsules was verified by
      confocal laser scanning microscopy (CLSM) and scanning force microscopy (SFM).
      The resulting hollow PSS/PAH/CR/PDDA capsules displayed a sensitive response to
      visible light. Optical changes of the hollow capsules prior to and after the
      photoreaction were investigated in detail by means of UV-visible spectroscopy,
      CLSM, and SFM. It was found that the photochemical reaction of the assembled
      hollow capsules depends strongly on the matrix. Qualitative results on the
      permeability of the hollow capsule walls with CR as one component indicate that
      the permeability of the walls can be easily photo-controlled at varying
      irradiation time intervals without addition of external chemicals.

PMID- 15252786
TI  - Mechanism of the hydrogen transfer from the OH group to oxygen-centered radicals:
      proton-coupled electron-transfer versus radical hydrogen abstraction.
AB  - High-level ab initio electronic structure calculations have been carried out with
      respect to the intermolecular hydrogen-transfer reaction HCOOH+.OH-->HCOO.+H(2)O
      and the intramolecular hydrogen-transfer reaction .OOCH2OH-->HOOCH(2)O.. In both
      cases we found that the hydrogen atom transfer can take place via two different
      transition structures. The lowest energy transition structure involves a proton
      transfer coupled to an electron transfer from the ROH species to the radical,
      whereas the higher energy transition structure corresponds to the conventional
      radical hydrogen atom abstraction. An analysis of the atomic spin population,
      computed within the framework of the topological theory of atoms in molecules,
      suggests that the triplet repulsion between the unpaired electrons located on the
      oxygen atoms that undergo hydrogen exchange must be much higher in the transition
      structure for the radical hydrogen abstraction than that for the proton-coupled
      electron-transfer mechanism. It is suggested that, in the gas phase, hydrogen
      atom transfer from the OH group to oxygen-centered radicals occurs by the proton
      coupled electron-transfer mechanism when this pathway is accessible.

PMID- 15252787
TI  - Weak hydrogen bridges: a systematic theoretical study on the nature and strength
      of C--H...F--C interactions.
AB  - We present a comparative study on the nature and strength of weak hydrogen
      bonding between the C(sp3)-H, C(sp2)-H, and C(sp)-H donor bonds and F-C(sp3)
      acceptors. The series of molecules CH3F.CH4 (2 a, 2 b), CH3F.C2H4 (3), CH3F.C2H2
      (4), as well as model complexes of experimentally characterized 2-fluoro-2
      phenylcyclopropane derivatives, C3H6.C3H5F (5 a, 5 b) and C3H5F.C3H5F (6) were
      investigated. Comparative studies were also performed for two conformers of the
      methane dimer (1 a, 1 b). The calculations were carried out in hierarchies of
      basis sets [SV(d,p), TZV(d,p), aug-TZV(d,p), TZV(2df,2pd), aug-TZV(2df,2pd),
      QZV(3d2fg,2pd), aug-QZV(3d2fg,2pdf)] by means of ab initio [HF, MP2, QCISD,
      QCISD(T)] methods and density functional theory (DFT/B3LYP, DFT/PBE). It is shown
      that well-balanced basis sets of at least TZV(2df,2pd) quality are needed for a
      proper description of the weakly bonded systems. In the case of 2, 3, 5, and 6,
      the dispersion interaction is the dominant term of the entire attraction, which
      is not accounted for at the B3LYP level. Significant electrostatic contributions
      are observed for 6 and 3. For 4, these forces have a dominating contribution to
      the hydrogen bonding. The C(sp)--H...F--C(sp(3)) interaction in 4, though weak,
      exhibits the same characteristics as conventional hydrogen bridges. Despite
      showing longer H.F/H contacts compared to 1 a, 2 a, and 5 a the bifurcated
      structures, 1 b, 2 b, 5 b, are characterized by larger dispersion interactions
      leading to stronger bonding. For the systems with only one H.F contact, the
      MP2/QZV(3d2fg,2pd) interaction energy increases in the order 2 a (-1.62 kJ mol(
      1)), 3 (-2.79 kJ mol(-1)), 5 a (-5.97 kJ mol(-1)), 4 (-7.25 kJ mol(-1)), and 6 (
      10.02 kJ mol(-1)). This contradicts the estimated proton donor ability of the C-
      H bonds (2 a<5 a<3<6<4).

PMID- 15252788
TI  - On the importance of electron correlation effects for the pi-pi interactions in
      cyclophanes.
AB  - Correlated ab initio quantum chemical methods based on second-order perturbation
      theory and density functional theory (DFT) together with large atomic orbital
      (AO) basis sets are used to calculate the structures of four cyclophanes with two
      aromatic rings and one sulphur-containing phane with one aromatic ring. The
      calculated geometrical data for [2.2]paracyclophane, cyclophane (superphane),
      8,16-dimethyl[2.2]metacyclophane, 16-methyl[2.2]metaparacyclophane, and 2,6,15
      trithia[3(4,10)][7]metacyclophane are compared to experimental data from X-ray
      crystal structure determinations. In all cases, very accurate theoretical
      predictions are obtained from the recently developed spin-component-scaled MP2
      (SCS-MP2) method, in which the deviations are within the experimental accuracy
      and expected crystal-packing or vibrational effects. Especially the inter-ring
      distances, which are determined by a detailed balance between attractive van der
      Waals (dispersive) and repulsive (Pauli) contributions, are very sensitive to the
      level of theory employed. While standard MP2 theory in general overestimates the
      dispersive interactions (pi-pi correlations) between the two aromatic rings
      leading to too short distances (between 3 and 8 pm), the opposite is observed for
      DFT methods (errors up to 15 pm). This indicates that an explicit account of
      dispersive-type electron correlation effects between the clamped aromatic units
      is essential for a quantitative description of cyclophane structures. In order to
      distinguish these effects from "normal" van der Waals interactions, the term
      "overlap-dispersive" interaction may be employed. The popular B3 LYP hybrid
      density functional offers no advantage over the pure PBE functional that at least
      qualitatively accounts for some of the dispersive effects. The use of properly
      polarized AO basis sets of at least valence-triple-zeta quality is strongly
      recommended to obtain quantitative predictions with traditional wave function
      methods.

PMID- 15252789
TI  - Matrix reactivity of Al and Ga atoms (M) in the presence of silane: generation
      and characterization of the eta2-coordinated complex M.SiH4, the insertion
      product HMSiH3, and the MI species MSiH3 in a solid argon matrix.
AB  - Matrix isolation experiments give evidence for the formation of the loosely
      bonded metal-silane complex M.SiH(4) by the spontaneous reaction of Al or Ga
      atoms (M) with silane in a solid Ar matrix at 12 K; however, Ga(2) appears to
      insert spontaneously into an Si--H bond to form HGaGaSiH(3), probably with the
      structure HGa(micro-SiH(3))Ga. In M.SiH(4) the metal atom is eta(2)-coordinated
      by the silane, resulting in a species with C(2v) symmetry. The complex has a
      distinctive photochemistry: it can be converted on photolysis at lambda
      approximately 410 or approximately 254 nm to its tautomer, HMSiH(3), which also
      has a doublet ground electronic state and from which it can be regenerated with
      lambda approximately 580 nm radiation. Broadband UV-visible photolysis
      (lambda=200-800 nm) results in decomposition of HMSiH(3), the univalent species
      MSiH(3) being the only detectable product. The experimental data collected for
      several silane isotopomers (SiH(4), SiD(4), and SiD(3)H) and different reagent
      concentrations, together with the results of sophisticated quantum chemical
      calculations, are used to explore in detail the properties of the detected
      species and the reaction pathways compassing their formation.

PMID- 15252790
TI  - Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4
      bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes
      and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by
      cyclodialkenylation.
AB  - 1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives
      2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared
      and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply
      substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented
      reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated
      during the reaction and behaved formally as a one-carbon unit; the N==O moiety of
      PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different
      reactivities among these three types of reagents 1, 2 and 3 were revealed. The
      1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4
      dimagnesium reagents 2 reacted with aldehydes, but not ketones; the
      metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did
      react with ketones.

PMID- 15252791
TI  - Low-lying excited states and primary photoproducts of [Os3(CO)10(s-cis-L)]
      (L=cyclohexa-1,3-diene, buta-1,3-diene)] clusters studied by picosecond time
      resolved UV/Vis and IR spectroscopy and by density functional theory.
AB  - Combined picosecond transient absorption and time-resolved infrared studies were
      performed, aimed at characterising low-lying excited states of the cluster
      [Os(3)(CO)(10)(s-cis-L)] (L=cyclohexa-1,3-diene, 1) and monitoring the formation
      of its photoproducts. Theoretical (DFT and TD-DFT) calculations on the closely
      related cluster with L=buta-1,3-diene (2') have revealed that the low-lying
      electronic transitions of these [Os(3)(CO)(10)(s-cis-1,3-diene)] clusters have a
      predominant sigma(core)pi*(CO) character. From the lowest sigmapi* excited state,
      cluster 1 undergoes fast Os-Os(1,3-diene) bond cleavage (tau=3.3 ps) resulting in
      the formation of a coordinatively unsaturated primary photoproduct (1 a) with a
      single CO bridge. A new insight into the structure of the transient has been
      obtained by DFT calculations. The cleaved Os-Os(1,3-diene) bond is bridged by the
      donor 1,3-diene ligand, compensating for the electron deficiency at the
      neighbouring Os centre. Because of the unequal distribution of the electron
      density in transient 1 a, a second CO bridge is formed in 20 ps in the
      photoproduct [Os(3)(CO)(8)(micro-CO)(2)(cyclohexa-1,3-diene)] (1 b). The latter
      compound, absorbing strongly around 630 nm, mainly regenerates the parent cluster
      with a lifetime of about 100 ns in hexane. Its structure, as suggested by the DFT
      calculations, again contains the 1,3-diene ligand coordinated in a bridging
      fashion. Photoproduct 1 b can therefore be assigned as a high-energy coordination
      isomer of the parent cluster with all Os-Os bonds bridged.

PMID- 15252792
TI  - Supramolecular porphyrin assemblies through amidinium-carboxylate salt bridges
      and fast intra-ensemble excited energy transfer.
AB  - Well-defined supramolecular assemblies of Zn and free-base porphyrins are
      constructed through the formation of amidinium-carboxylate salt bridges. A one-to
      one donor-acceptor pair and a four-to-one antenna-type assembly are investigated.
      The steady-state and time-resolved fluorescence measurements unequivocally showed
      that efficient singlet-singlet excited energy transfer from the Zn-porphyrin
      complex to the free-base porphyrin takes place in these assemblies. Indeed, the
      observed energy-transfer rates in both types of assemblies are much faster than
      those the Forster mechanism would suggest, implying the involvement of an
      intermolecular through-bond mechanism.

PMID- 15252793
TI  - Biocatalytic asymmetric rearrangement of a methylene-interrupted bis-epoxide:
      simultaneous control of four asymmetric centers through a biomimetic reaction
      cascade.
AB  - Asymmetric enzyme-catalyzed hydrolysis of methylene-interrupted bis-epoxides 1 a
      and 1 b catalyzed by bacterial epoxide hydrolases furnished tetrahydrofuran
      derivatives 2 a and 2 b through a hydrolysis-rearrangement cascade. Whereas
      racemic bis-oxiranes 1 b-d underwent kinetic resolution with moderate
      stereoselectivities to yield products with up to 92 % ee and 66 % de: meso-bis
      oxirane cis,cis-1 a was transformed into (6R,7R,9S,10S)-2 a in 94 % ee and 89 %
      de at high conversion (85 %) by Rhodococcus sp. CBS 717.73 as the major product.
      The reaction sequence resembles a biomimetic reaction cascade and provides an
      efficient entry into the structural core of annonaceous acetogenins with
      simultaneous control of four stereocenters.

PMID- 15252794
TI  - Ionic liquids with symmetrical dialkoxymethyl-substituted imidazolium cations.
AB  - A new one-step procedure is described for the synthesis of disubstituted
      imidazolium chlorides. 1,3-Dialkoxymethylimidazolium chlorides thus obtained can
      be employed as synthetic precursors of symmetrical ILs. The salts have been found
      to exhibit antimicrobial activity and an antielectrostatic effect. Their
      densities and viscosities have been determined and are reported herein. It has
      also been demonstrated that the ILs can be decomposed using an aqueous solution
      of KMnO(4). For each IL, the permanganate index (I(Mn)) has been estimated, which
      varies with the structure of cation. The only limitation of I(Mn) is the degree
      to which the IL dissolves in water.

PMID- 15252795
TI  - Spectral, structural, and electrochemical properties of ruthenium porphyrin
      diaryl and aryl(alkoxycarbonyl) carbene complexes: influence of carbene
      substituents, porphyrin substituents, and trans-axial ligands.
AB  - A wide variety of ruthenium porphyrin carbene complexes, including
      [Ru(tpfpp)(CR(1)R(2))] (CR(1)R(2) = C(p-C(6)H(4)Cl)(2) 1 b, C(p-C(6)H(4)Me)(2) 1
      c, C(p-C(6)H(4)OMe)(2) 1 d, C(CO(2)Me)(2) 1 e, C(p-C(6)H(4)NO(2))CO(2)Me 1 f, C(p
      C(6)H(4)OMe)CO(2)Me 1 g, C(CH==CHPh)CO(2)CH(2)(CH==CH)(2)CH(3) 1 h),
      [Ru(por)(CPh(2))] (por=tdcpp 2 a, 4-Br-tpp 2 b, 4-Cl-tpp 2 c, 4-F-tpp 2 d, tpp 2
      e, ttp 2 f, 4-MeO-tpp 2 g, tmp 2 h, 3,4,5-MeO-tpp 2 i), [Ru(por)[C(Ph)CO(2)Et]]
      (por=tdcpp 2 j, tmp 2 k), [Ru(tpfpp)(CPh(2))(L)] (L = MeOH 3 a, EtSH 3 b, Et(2)S
      3 c, MeIm 3 d, OPPh(3) 3 e, py 3 f), and [Ru(tpfpp)[C(Ph)CO(2)R](MeOH)] (R =
      CH(2)CH==CH(2) 4 a, Me 4 b, Et 4 c), were prepared from the reactions of
      [Ru(por)(CO)] with diazo compounds N(2)CR(1)R(2) in dichloromethane and, for 3
      and 4, by further treatment with reagents L. A similar reaction of
      [Os(tpfpp)(CO)] with N(2)CPh(2) in dichloromethane followed by treatment with
      MeIm gave [Os(tpfpp)(CPh(2))(MeIm)] (3 d-Os). All these complexes were
      characterized by (1)H NMR, (13)C NMR, and UV/Vis spectroscopy, mass spectrometry,
      and elemental analyses. X-ray crystal structure determinations of 1 d, 2 a,i, 3
      a, b, d, e, 4 a-c, and 3 d-Os revealed Ru==C distances of 1.806(3)-1.876(3) A and
      an Os==C distance of 1.902(3) A. The structure of 1 d in the solid state features
      a unique "bridging" carbene ligand, which results in the formation of a one
      dimensional coordination polymer. Cyclic voltammograms of 1 a-c, g, 2 a-d, g-k, 3
      b-d, 4 a, b, and 3 d-Os show a reversible oxidation couple with E(1/2) values in
      the range of 0.06-0.65 V (vs Cp(2)Fe(+/0)) that is attributable to a metal
      centered oxidation. The influence of carbene substituents, porphyrin
      substituents, and trans-ligands on the Ru==C bond was examined through comparison
      of the chemical shifts of the pyrrolic protons in the porphyrin macrocycles ((1)H
      NMR) and the M==C carbon atoms ((13)C NMR), the potentials of the metal-centered
      oxidation couples, and the Ru==C distances among the various ruthenium porphyrin
      carbene complexes. A direct comparison among iron, ruthenium, and osmium
      porphyrin carbene complexes is made.

PMID- 15252796
TI  - Ruthenium(II) as a novel "labile" partner in thermodynamic self-assembly of
      heterobimetallic d-f triple-stranded helicates.
AB  - Unsymmetrical substituted bidentate benzimidazol-2-ylpyridine ligands L2 and L3
      react with [Ru(dmso)(4)Cl(2)] in ethanol to give statistical 1:3 mixtures of fac
      [Ru(Li)(3)](2+) and mer-[Ru(Li)(3)](2+) (i=2, 3; DeltaGtheta(isomerisation)=-2.7
      kJ mol(-1)). In more polar solvents (acetonitrile, methanol), the free energy of
      the facial<=>meridional isomerisation process favours mer-[Ru(Li)(3)](2+), which
      is the only isomer observed in solution at the equilibrium
      (DeltaGtheta(isomerisation)< or = -11.4 kJ mol(-1)). Since the latter process
      takes several days for [Ru(L2)(3)](2+), fac-[Ru(L2)(3)](2+) and mer
      [Ru(L2)(3)](2+) have been separated by chromatography, but the 28-fold increase
      in velocity observed for [Ru(L3)(3)](2+) provides only mer-[Ru(L3)3](ClO(4))2
      after chromatography (RuC(60)H(51)N(9)O(8)Cl(2), monoclinic, P2(1)/n, Z=4). The
      facial isomer can be stabilised when an appended tridentate binding unit,
      connected at the 5-position of the benzimidazol-2-ylpyridine unit in ligand L1,
      interacts with nine-coordinate lanthanides(III). The free energy of the
      facial<=>meridional isomerisation is reversed (DeltaGtheta(isomerisation)> or
      =11.4 kJ mol(-1)), and the Ru--N bonds are labile enough to allow the
      quantitative thermodynamic self-assembly of HHH-[RuLu(L1)(3)]5+ within hours
      ([RuLu(L1)3](CF(3)SO(3))(4.5)Cl(0.5)(CH(3)OH)(2.5):
      RuLuC(106)H(109)Cl(0.5)N(21)O(19)S(4.5)F(13.5), triclinic, P(-)1, Z=2).
      Electrochemical and photophysical studies show that the benzimidazol-2-ylpyridine
      units in L1-L3 display similar pi-acceptor properties to, but stronger pi-donor
      properties than, those found in 2,2'-bipyridine. This shifts the intraligand pi-
      >pi* and the MLCT transitions toward lower energies in the pseudo-octahedral
      [Ru(Li)(3)](2+) (i=2, 3) chromophores. The concomitant short lifetime of the
      (3)MLCT excited state points to efficient, thermally activated quenching via low
      energy Ru-centred d-d states, a limitation which is partially overcome by
      mechanical coupling in HHH-[RuLu(L1)(3)]5+.

PMID- 15252797
TI  - The immunogenicity of the tumor-associated antigen Lewis(y) may be suppressed by
      a bifunctional cross-linker required for coupling to a carrier protein.
AB  - A Lewis(y) (Le(y)) tetrasaccharide modified by an artificial aminopropyl spacer
      was synthesized by a highly convergent approach that employed a levulinoyl ester
      and a 9-fluorenylmethoxycarbonate for temporary protection of the hydroxy groups
      and a trichloroethyloxycarbonyl as an amino protecting group. The artificial
      aminopropyl moiety was modified by a thioacetyl group, which allowed efficient
      conjugation to keyhole limpet hemocyanin (KLH) modified by electrophilic 4
      (maleimidomethyl)cyclohexane-1-carboxylate (MI). Mice were immunized with the KLH
      MI-Le(y) antigen. A detailed analysis of sera by ELISA established that a strong
      immunoglobulin G (IgG) antibody response was elicited against the linker region.
      The use of a smaller and more flexible 3-(bromoacetamido)propionate for the
      attachment of Le(y) to KLH not only reduced the IgG antibody response against the
      linker but also led to a significantly improved immune response against the Le(y)
      antigen. This study shows that highly antigenic linkers suppress antibody
      responses to weak antigens such as self-antigens.

PMID- 15252798
TI  - A general atmospheric pressure chemical vapor deposition synthesis and
      crystallographic study of transition-metal sulfide one-dimensional
      nanostructures.
AB  - A series of transition-metal sulfide one-dimensional (1D) nanostructures have
      been synthesized by means of a general atmospheric pressure, chemical vapor
      deposition (APCVD) strategy. Vapour-liquid-solid (VLS) and vapour-solid (VS)
      mechanisms, along with the results of SEM and TEM observations, were used to
      explain the formation of these nanostructures. The regularity of the growth in
      the direction of the hexagonal nanowire is explored; we find that it prefers to
      grow along (1 0 0), (1 1 0), or (0 0 x) directions owing to particular crystal
      structures. The adopted synthetic route was expected to provide abundant useful
      1D building blocks for the research of mesoscopic physics and fabrication of
      nanoscale devices.

PMID- 15252799
TI  - A novel method to synthesize polystyrene nanospheres immobilized with silver
      nanoparticles by using compressed CO2.
AB  - In this work, a novel route to synthesize polymer/metal composite nanospheres has
      been proposed. This method combines the advantages that the polymer chains
      collapse and entangle in the presence of compressed CO(2), which acts as
      antisolvent, and the metal nanoparticles and polymers can be precipitated
      simultaneously from micellar solutions by the easy control of CO(2) pressure.
      Ag/polystyrene (PS) nanocomposites have been successfully prepared using this
      method. The transmission electronic micrographs (TEM) of the obtained
      nanocomposites show that the smaller Ag nanoparticles are immobilized by PS
      nanospheres of about 50 nm; the phase structure was characterized by X-ray
      diffraction (XRD). The Ag/PS nanocomposites show absorption properties at a
      wavelength of approximately 417 nm. The results of X-ray photoelectron spectra
      (XPS) and FT-IR spectra indicate that there is no chemical linkage or strong
      interaction between PS and Ag nanoparticles in the resultant products. This
      method has many potential advantages for applications and may easily be applied
      to the preparation of a range of inorganic/ polymer composite nanoparticles.

PMID- 15252800
TI  - Yttrium and lanthanide diphosphanylamides: syntheses and structures of complexes
      with one [(Ph2P)2N]- ligand in the coordination sphere.
AB  - Treatment of the recently reported potassium salt [K(thf)(n)][N(PPh(2))(2)]
      (n=1.25, 1.5) with anhydrous yttrium or lanthanide trichlorides in THF leads
      after crystallization from THF/n-pentane (1:2) to the monosubstituted
      diphosphanylamide complexes [LnCl(2)[(Ph(2)P)(2)N](thf)(3)] (Ln=Y, Sm, Er, Yb).
      The single-crystal X-ray structures of these complexes show that the metal atoms
      are surrounded by seven ligands in a distorted pentagonal bipyramidal
      arrangement, in which the chlorine atoms are located in the apical positions. The
      diphosphanylamide ligand is always eta(2)-coordinated through the nitrogen atom
      and one phosphorus atom. Further reaction of [SmCl(2)[(Ph(2)P)(2)N](thf)(3)] with
      K(2)C(8)H(8) or reaction of [LnI(eta(8)-C(8)H(8))(thf)(3)] with
      [K(thf)(n)][N(PPh(2))(2)] in THF gives the corresponding cyclooctatetraene
      complexes [Ln[(Ph(2)P)(2)N](eta(8)-C(8)H(8))(thf)(2)] (Ln=La, Sm). The single
      crystals of these compounds contain enantiomerically pure complexes. Both
      compounds adopt a four-legged piano-stool conformation in the solid state. The
      structures of the A and the C enantiomers were established by single-crystal X
      ray diffraction. The more soluble bistrimethylsilyl cyclooctatetraene complex
      [Y[(Ph(2)P)(2)N](eta(8)-1,4-(Me(3)Si)(2)C(8)H(6))(thf)(2)] was obtained by
      transmetallation of Li(2)[1,4-(Me(3)Si)(2)C(8)H(6)] with anhydrous yttrium
      trichloride in THF followed by the addition of one equivalent of
      [K(thf)(n)][N(PPh(2))(2)]. The (89)Y NMR signal of the complex is split up into a
      triplet, supporting other observations that the phosphorus atoms are chemically
      equivalent in solution and, thus, dynamic behavior of the ligand in solution can
      be anticipated.

PMID- 15252801
TI  - Molecular evolution using intramolecular acyl migration on myo-inositol benzoates
      with thermodynamic and kinetic selectors.
AB  - A molecular evolution model was successfully demonstrated by combining the
      intramolecular acyl migration on inositol tribenzoates and boron selectors. The
      addition of boric acid to 12 members of DCL (dynamic combinatorial library)
      induced the dramatic amplification of myo-I(2,4,6)Bz(3) (1) with up to 94 % under
      thermodynamic (see Figure 1 c) control while a portion of phenyl boronic acid
      caused two significant different distributions: under kinetic control, the pre
      equilibrium of DCL shifted to induce the exclusive amplification of 1,4,6
      tribenzoyl myo-inositol (7) with decrease of other members up to 82 % from the
      mixture (see Figure 2 b), and changed gradually to form 2,4,6-tribenzoyl myo
      inositol (1) with up to 96 % under thermodynamic control (Figure 2 c).

PMID- 15252802
TI  - Selective formation of AAB- and ABC-type heterotrimeric alpha-helical coiled
      coils.
AB  - The alpha-helical coiled coils have a representative amino acid sequence of
      (abcdefg)(n) heptad repeats. We previously reported that two peptides named IZ-2A
      and IZ-2W formed an (IZ-2A)(2)/IZ-2W heterotrimer with an Ala-Ala-Trp interaction
      in the hydrophobic core. In this paper, we describe the selective formation of
      AAB- and ABC-type heterotrimers. To increase the selectivity of the AAB-type
      heterotrimeric formation, Lys residues at the f position were mutated to either
      an Ala or a Gln residue to form IZ-2A(fA) or IZ-2W(fQ). Separately, both IZ
      2A(fA) and IZ-2W(fQ) have a random structure at pH 7 and 20 degrees C. However,
      together IZ-2A(fA) and IZ-2W(fQ) form a 2:1 complex with a thermal transition
      midpoint (Tm) of 48 degrees C. This procedure was applied to prepare the ABC-type
      heterotrimer, in which two sets of Ala-Ala-Trp interactions were designed in the
      hydrophobic core. Interhelical interaction between the e and g positions and the
      alpha-helical propensity of the amino acid at the f position were also considered
      in the design. The resultant three peptides selectively formed the ABC-type
      heterotrimer with a Tm of 51 degrees C. Other peptide combinations had random
      coil properties.

PMID- 15252803
TI  - Synthesis of an enzyme-like imprinted polymer with the substrate as the template,
      and its catalytic properties under aqueous conditions.
AB  - Transition state analogues (TSAs) have long been regarded as ideal templates for
      the preparation of catalytically active synthetic imprinted polymers. In the
      current work, however, a new type of molecularly imprinted polymer (MIP) was
      synthesized with the substrate (homovanillic acid, HVA) as the template and hemin
      introduced as the catalytic center, with the use of plural functional monomers to
      prepare the active sites. The MIP successfully mimicked natural peroxidase,
      suggesting that it may not be imperative to employ a TSA as the template when
      preparing enzyme-like imprinted polymers and that the imprinted polymer matrix
      provided an advantageous microenvironment around the catalytic center (hemin),
      essentially similar to that supplied by apo-proteins in natural enzymes.
      Significantly, by taking advantage of the special structure of hemin and multiple
      site interactions provided by several functional monomers, the intrinsic
      difficulties for MIPs in recognizing template molecules in polar solutions were
      overcome. The newly developed polymer showed considerable recognizing ability
      toward HVA, catalytic activity, substrate specificity and also stability, which
      are the merits lacked by the natural peroxidase. Meanwhile, the ease of recovery
      and reuse the MIP implies the potential for industrial application.

PMID- 15252804
TI  - A photoswitchable rotaxane with a folded molecular thread.
AB  - Novel [2]rotaxanes containing the tetracationic cyclophane cyclobis(paraquat-4,4
      biphenylene) and a dumbbell-shaped molecular thread incorporating a photoactive
      diarylcycloheptatriene station as well as a photoinactive anisol station have
      been synthesized with yields of nearly 50 % by the alkylative endcapping method.
      The rotaxane was transformed into the related rotaxane incorporating a diaryl
      tropylium unit by electrochemical oxidation. The precursor of the
      cycloheptatrienyl rotaxane, the related pseudorotaxane, and the rotaxanes
      incorporating the diarylcycloheptatriene and the corresponding tropylium unit
      were characterized by (1)HNMR spectroscopy and UV/Vis spectroscopy. According to
      the NMR spectra, both the cycloheptatriene and the tropylium rotaxane possess a
      folded conformation enabling the tetracationic cyclophane to interact with two
      stations. The diarylcycloheptatriene station is incorporated inside the cavity of
      the cyclophane and the anisol station resides alongside the bipyridinium unit of
      the cyclophane. In contrast, the anisol station is inside the cyclophane in the
      tropylium rotaxane. The exchange between both conformations can be achieved by
      introducing the methoxy leaving group into the cycloheptatriene ring; the
      tropylium rotaxane is generated by photoheterolysis of this methoxy-substituted
      rotaxane, which reacts thermally back to the cycloheptatriene rotaxane, thus
      closing the switching cycle. These induced conformational changes achieve a so
      called molecular machine.

PMID- 15252805
TI  - Cytotoxic trans-oriented platinum complexes only form adducts with single
      stranded oligodeoxynucleotides.
AB  - The reactions of the anticancer complex trans-[PtCl(2)[(E)-HN==C(OMe)Me](2)]
      (trans-EE) with both single-stranded and double-stranded deoxyribonucleotides
      have been studied by HPLC and 2D [(1)H,(15)N] HMQC NMR spectroscopy and compared
      with those of cis-[PtCl(2)(NH(3))(2)] (cis-DDP). Reactions of trans-EE with the
      single-stranded oligonucleotides d(CCTCGCTCTC) and d(CCTGGTCC) proceed rapidly
      through solvolysis of the starting substrate and subsequent formation of G
      N7/monochloro trans-EE adducts. The rate of reaction is comparable to that of
      formation of an adduct from trans-EE and the dinuclotide d(ApG). Quite
      unexpectedly, the double-helical duplexes, d(TATGGTACCATA)(2) and
      d(TATGGCCATA)(2), with no terminal G residues, are practically inert towards
      trans-EE, and only minor species (< 5 % as estimated from HPLC traces) appear
      during 24 h reaction time. However, the duplexes d[(CCTCGCTCTC). (GAGAGCGAGG)]
      and d(GATAGGCCTATC)(2), which contain both terminal and central G residues,
      undergo platination only at the terminal, solvent-exposed, G residues, thereby
      confirming that the interior of the duplex is not accessible to trans-EE due to
      steric hindrance. In contrast, cis-DDP was found to bind exclusively to the
      central GG pair in d(GATAGGCCTATC)(2).

PMID- 15252806
TI  - Lanthanide chelates containing pyridine units with potential application as
      contrast agents in magnetic resonance imaging.
AB  - A new pyridine-containing ligand, N,N'-bis(6-carboxy-2
      pyridylmethyl)ethylenediamine-N,N'-diacetic acid (H(4)L), has been designed for
      the complexation of lanthanide ions. (1)H and (13)C NMR studies in D(2)O
      solutions show octadentate binding of the ligand to the Ln(III) ions through the
      nitrogen atoms of two amine groups, the oxygen atoms of four carboxylates, and
      the two nitrogen atoms of the pyridine rings. Luminescence measurements
      demonstrate that both Eu(III) and Tb(III) complexes are nine-coordinate, whereby
      a water molecule completes the Ln(III) coordination sphere. Ligand L can
      sensitize both the Eu(III) and Tb(III) luminescence; however, the quantum yields
      of the Eu(III)- and Tb(III)-centered luminescence remain modest. This is
      explained in terms of energy differences between the singlet and triplet states
      on the one hand, and between the 0-phonon transition of the triplet state and the
      excited metal ion states on the other. The anionic [Ln(L)(H2O)]- complexes
      (Ln=La, Pr, and Gd) were also characterized by theoretical calculations both in
      vacuo and in aqueous solution (PCM model) at the HF level by means of the 3-21G*
      basis set for the ligand atoms and a 46+4 f(n) effective core potential for the
      lanthanides. The structures obtained from these theoretical calculations are in
      very good agreement with the experimental solution structures, as demonstrated by
      paramagnetic NMR measurements (lanthanide-induced shifts and relaxation-rate
      enhancements). Data sets obtained from variable-temperature (17)O NMR at 7.05 T
      and variable-temperature (1)H nuclear magnetic relaxation dispersion (NMRD) on
      the Gd(III) complex were fitted simultaneously to give insight into the
      parameters that govern the water (1)H relaxivity. The water exchange rate
      (k(298)(ex)=5.0 x 10(6) s(-1)) is slightly faster than in [Gd(dota)(H2O)]-
      (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). Fast
      rotation limits the relaxivity under the usual MRI conditions.

PMID- 15252808
TI  - Glial control of synaptic function.

PMID- 15252809
TI  - Role for glia in synaptogenesis.
AB  - Nearly one-half of the cells in a human brain are astrocytes, but the function of
      these little cells remains a great mystery. Astrocytes form an intimate
      association with synapses throughout the adult CNS, where they help regulate ion
      and neurotransmitter concentrations. Recent in vitro studies, however, have found
      that astrocytes also exert powerful control over the number of CNS synapses that
      form, are essential for postsynaptic function, and are required for synaptic
      stability and maintenance. Moreover, recent studies increasingly implicate
      astrocytes in vivo as participants in activity-dependent structural and
      functional synaptic changes throughout the nervous system. Taken together, these
      data force us to rethink the role of glia. We propose that astrocytes should not
      be viewed primarily as support cells, but rather as cells that actively control
      the structural and functional plasticity of synapses in developing and adult
      organisms.

PMID- 15252810
TI  - Role of glial amino acid transporters in synaptic transmission and brain
      energetics.
AB  - This article reviews how the uptake of neurotransmitter by glial amino acid
      transporters limits the spatial spread of transmitter to preserve the independent
      operation of nearby synapses, temporally shapes postsynaptic currents, and
      regulates the effects of tonic transmitter release. We demonstrate the importance
      of amino acid uptake and recycling mechanisms for preventing the loss of
      energetically costly neurotransmitter from the brain, and also examine the
      suggestion that glutamate uptake into glia plays a key role in regulating the
      energy production of the brain. Finally, we assess the role of glial amino acid
      transporters in transmitter recycling pathways.

PMID- 15252811
TI  - Astrocyte responses to neuronal activity.
AB  - During the past few years, it has been established that astrocytes sense neuronal
      activity and are involved in signal transmission. Neuronal stimulation triggered
      electrophysiological and/or Ca(2+) responses in astrocyte cultures and in acute
      brain slices. Present even within one given brain region, different pathways of
      neuron-to-astrocyte communication involving different receptor systems have been
      described. These mechanisms include glutamatergic and NO-mediated signaling.
      Neuron-to-astrocyte signaling can be confined to subcellular compartments, the
      microdomains, or it can activate the entire cell. It can even trigger a
      multicellular response in astrocytes, a Ca(2+) wave. This form of astrocyte long
      range signal propagation can occur independently, in pure astrocyte cultures, but
      it can also be triggered by neuronal activity. Astrocytes also exhibit
      spontaneous Ca(2+) activity. Neuronal activity in acute brain slices can organize
      this activity into complex synchronous networks. One of the functional
      consequences of neuron-to-astrocyte signaling might be the neuronal control of
      microcirculation using astrocytes as a mediator.

PMID- 15252812
TI  - Defining pathways of loss and secretion of chemical messengers from astrocytes.
AB  - It is becoming evident that glia, and astrocytes in particular, are intimately
      involved in neuronal signaling. Astrocytic modulation of signaling in neurons
      appears to be mediated by the release of neuroactive compounds such as the
      excitatory amino acid glutamate. Release of these transmitters appears to be
      driven by two different processes: (1) a volume regulatory response triggered by
      hypo-osmotic conditions that leads to the release of osmotically active solutes
      from the cytoplasm into the extracellular space, and (2) intracellular calcium
      dependent vesicle-mediated excytotic release. The regulatory volume decrease may
      be mediated by any of several different pathways that increase membrane
      permeability, thus allowing osmolytes to travel down their concentration gradient
      into the extracellular space. Such pathways include anion channels, hemichannels,
      P2X receptor channels, and transporters or multidrug resistance proteins. The
      excytotic release process may use calcium triggered synaptic like vesicle fusion
      or alterations in constitutive vesicle trafficking to the membrane. Determining
      the contribution of any of these release mechanisms requires agents that can be
      used to specifically block pathways of interest. Currently, many of the
      pharmacological compounds being used exhibit a great deal of cross-reactivity
      between several of these pathways. For example, the popular anion channel
      inhibitor 5-nitro-2-(3-phenyl-propylamino)benzoic acid (NPPB) is an efficient
      blocker of both hemichannels and vesicle loading. This demonstrates the need to
      more fully characterize the activities of the agents currently available and to
      choose pathway blockers carefully when designing experiments.

PMID- 15252813
TI  - Glial modulation of synaptic transmission in culture.
AB  - Accumulating evidence has demonstrated the existence of bidirectional
      communication between glial cells and neurons, indicating an important active
      role of glia in the physiology of the nervous system. Neurotransmitters released
      by presynaptic terminals during synaptic activity increase intracellular Ca(2+)
      concentration in adjacent glial cells. In turn, activated glia may release
      different transmitters that can feed back to neuronal synaptic elements,
      regulating the postsynaptic neuronal excitability and modulating neurotransmitter
      release from presynaptic terminals. As a consequence of this evidence, a new
      concept of the synaptic physiology, the tripartite synapse, has been proposed, in
      which glial cells play an active role as dynamic regulatory elements in
      neurotransmission. In the present article we review evidence showing the ability
      of astrocytes to modulate synaptic transmission directly, with the focus on
      studies performed on cell culture preparations, which have been proved extremely
      useful in the characterization of molecular and cellular processes involved in
      astrocyte-mediated neuromodulation.

PMID- 15252814
TI  - Glial modulation of synaptic transmission in the hippocampus.
AB  - For many years, astrocytes and oligodendrocytes were considered the inert
      partners of neurons in the central nervous system (CNS), but several recent
      studies have dramatically challenged this view. Glial cells express a large
      number of different voltage- and ligand-gated ion channels (Verkhratsky and
      Steinhauser. Brain Res Rev 32:380-412, 2000) as well as G-protein-coupled
      receptors (Verkhratsky et al. Physiol Rev 78:99-141, 1998)-machinery necessary to
      sense and respond to neuronal activity. These findings raised the fundamental
      question as to whether glial receptors are stimulated under physiological
      conditions, and what sorts of events are triggered by such activation. During the
      early 1990s, P. Haydon and colleagues made the seminal observation that
      [Ca(2+)](i) rises in cultured astrocytes are associated with the release of
      glutamate, which suggested that astrocytes respond to activation and play active
      modulatory roles in intercellular communication (Parpura et al. Nature 369:744
      747, 1994). Subsequent studies performed in situ confirmed and extended this
      initial observation. In this review, we will focus specifically on the
      hippocampus and sum up evidence of bidirectional communication between astrocytes
      and neurons emerging from recent studies using acute slice preparations.

PMID- 15252815
TI  - Glial modulation of synaptic transmission: Insights from the supraoptic nucleus
      of the hypothalamus.
AB  - Astrocytes clear synaptically released glutamate from the extracellular space
      through high-affinity transporters present on their plasma membrane. By
      controlling the extracellular level of the main excitatory transmitter in the
      central nervous system, astrocytes thus contribute prominently to the regulation
      of overall cellular excitability and synaptic information processing. We recently
      investigated the influence of the glial environment on glutamatergic and
      GABAergic neurotransmission in the supraoptic nucleus of the rat hypothalamus
      under physiological conditions such as lactation that significantly reduce
      astrocytic coverage of its neurons. By performing electrophysiological analyses
      on this unique model of dynamic neuronal-glial interactions, we have been able to
      show that the fine astrocytic processes normally enwrapping synapses serve two
      important functions. First, they govern the level of activation of presynaptic
      metabotropic glutamate receptors on glutamatergic terminals, thereby regulating
      synaptic efficacy at excitatory synapses. Second, they act as a physical and
      functional barrier to diffusion in the extracellular space, limiting spillover of
      glutamate and other neuroactive substances and therefore contributing to the
      regulation of heterosynaptic transmission and intercellular communication.

PMID- 15252816
TI  - Glial modulation of synaptic transmission in the retina.
AB  - Glial modulation of synaptic transmission and neuronal excitability in the
      mammalian retina is mediated by several mechanisms. Stimulation of glial cells
      evokes Ca(2+) waves, which propagate through the network of retinal astrocytes
      and Muller cells and result in the modulation of the activity of neighboring
      ganglion cells. Light-evoked spiking is enhanced in some ganglion cells and
      depressed in others. A facilitation or depression of light-evoked excitatory
      postsynaptic currents is also seen in ganglion cells following glial stimulation.
      In addition, stimulation of glial cells evokes a sustained hyperpolarizing
      current in ganglion cells which is mediated by ATP release from Muller cells and
      activation of neuronal A(1) adenosine receptors. Recent studies reveal that light
      evoked activity in retinal neurons results in an increase in the frequency of
      Ca(2+) transients in Muller cells. Thus, there is two-way communication between
      neurons and glial cells, suggesting that glia contribute to information
      processing in the retina.

PMID- 15252817
TI  - D-Serine as a glial modulator of nerve cells.
AB  - Until the last decade, it was widely accepted that D-amino acids had no
      functional role in higher organisms, but that they were restricted to lower
      organisms, such as bacteria, where they are integrated into the proteoglycans of
      the cell wall. However, D-serine proved to be an effective coagonist at the
      "glycine-binding" site of the N-methyl-D-aspartate (NMDA) glutamate receptors,
      and this observation led to chemical analyses that have now revealed the presence
      of high levels of D-serine in the central nervous system, including many regions
      of the brain and retina. D-Serine has been localized to astrocytes and can be
      released by glutamate through stimulation of AMPA receptors. A new enzyme, serine
      racemase has been localized to glial cells and converts L-serine to D-serine.
      Degradation of D-serine takes place through D-amino acid oxidase, an enzyme once
      thought to metabolize D-amino acids from external sources. Although the "glycine
      binding" site of NMDA receptors was initially regarded as a saturated site,
      evidence in many brain regions has established that this site is not saturated
      and is therefore modulated by interactions between glial cells and neurons. In
      some, but not all, studies, D-serine enhances NMDA-mediated currents; a light
      evoked enhancement to NMDA currents has been reported in the retina. D-serine
      also plays a role in synaptic and cellular development, particularly in the
      cerebellum, where the normal developmental sequences underlying synapse formation
      onto Purkinje cells and the migration of granule cells are dependent on NMDA
      receptors during a time when high levels of D-serine are expressed in the
      Bergmann glia and other cerebellar astrocytes. D-serine must be added to the list
      of agents through which glial cells participate in controlling the excitability
      of neurons.

PMID- 15252818
TI  - Glial modulation of synaptic transmission at the neuromuscular junction.
AB  - The neuromuscular junction (NMJ) is a cholinergic synapse that controls muscle
      contraction. Glial cells, called perisynaptic Schwann cells, surround nerve
      terminals at the NMJ. Transmitter release induced by repetitive nerve
      stimulation, elicit a frequency-dependent activation of G-protein-coupled
      receptors on perisynaptic Schwann cells and the release of calcium from internal
      stores. In return, perisynaptic Schwann cells modulate synaptic activity during
      and following high-frequency stimulation through short-term plasticity. In the
      present review, we discuss evidence of glial involvement in the short-term
      plasticity at the NMJ and the potential impact of such modulation on synaptic
      efficacy.

PMID- 15252819
TI  - Synaptic signaling between neurons and glia.
AB  - Rapid signaling between vertebrate neurons occurs primarily at synapses,
      intercellular junctions where quantal release of neurotransmitter triggers rapid
      changes in membrane conductance through activation of ionotropic receptors. Glial
      cells express many of these same ionotropic receptors, yet little is known about
      how receptors in glial cells become activated in situ. Because synapses were
      thought to be the sole provenance of neurons, it has been assumed that these
      receptors must be activated following diffusion of transmitter out of the
      synaptic cleft, or through nonsynaptic mechanisms such as transporter reversal.
      Two recent reports show that a ubiquitous class of progenitors that express the
      proteoglycan NG2 (NG2 cells) engage in rapid signaling with glutamatergic and
      gamma-aminobutyric acid (GABA)ergic neurons through direct neuron-glia synapses.
      Quantal release of transmitter from neurons at these sites triggers rapid
      activation of aminomethylisoxazole propionic acid (AMPA) or GABA(A) receptors in
      NG2 cells. These currents exhibit properties consistent with direct rather than
      spillover-mediated transmission, and electron micrographic analyses indicate that
      nerve terminals containing clusters of synaptic vesicles form discrete junctions
      with NG2 cell processes. Although activation of AMPA or GABA(A) receptors
      depolarize NG2 cells, these receptors are more likely to serve as routes for ion
      flux rather than as current sources for depolarization, because the amplitudes of
      the synaptic transients are small and the resting membrane potential of NG2 cells
      is highly negative. The ability of both glutamate and GABA to influence the
      morphology, physiology, and development of NG2 cells in vitro suggests that this
      rapid form of signaling may play important roles in adapting the behavior of
      these cells to the needs of surrounding neurons in vivo.

PMID- 15252820
TI  - Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a
      pharmacokinetic evaluation of repeated drug concentration measurements during 6
      months of treatment for major depression.
AB  - Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment
      of major depression. Nevertheless, continuous follow-ups of drug concentrations
      prevailing in patients during the whole treatment period are not available.
      Hence, in a large phase IV clinical trial, a total of 353 patients with major
      depression were enrolled for a 6-month comparison of sertraline (50-150 mg daily)
      and paroxetine (20-60 mg daily). The present study reports the pharmacokinetic
      results of up to eight serum samples per patient. 1. A profound variability was
      found in the interindividual steady state and trough serum levels of sertraline,
      desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for
      sertraline, 51% for desmethylsertraline, 27% for the ratio
      desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day).
      The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%,
      indicating intraindividual metabolizing stability over time. Both sertraline and
      paroxetine displayed sex differences in the dose-concentration correlation. 2. It
      was possible to predict sertraline, but not paroxetine, steady state levels. 3.
      The terminal elimination t(1/2) for both drugs after 6 months of treatments was
      similar to data previously reported from short-term withdrawal studies. 4. No
      correlation between serum drug concentrations and clinical effect was detected
      for either sertraline or paroxetine. For the future, continuous efforts are
      warranted to perform PK investigations in the natural clinical setting in which
      the drugs are usually prescribed.

PMID- 15252821
TI  - Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients.
AB  - Cytochrome P450-2D6 may be involved in the metabolism of many drugs such as
      psychotropic drugs and its genetic polymorphism is responsible for inter
      individual differences in the therapeutic effect and toxicity of these drugs.
      Moreover with the same genetic basis, CYP2D6 metabolic capacity variations are
      observed. Different factors of variation may be involved, among them the
      prescribed drugs. The aim of this study was to compare the influence of two types
      of antidepressants, tricyclic (clomipramine) and serotonergic specific recapture
      inhibitor (SSRI) (fluoxetine), on the CYP2D6 metabolic capacity of depressed
      inpatients. The CYP2D6 phenotype (dextromethorphan test) was determined in 56
      genotyped (PCR-SSCP) depressed caucasian inpatients with a heterozygous genotype.
      Forty-five subjects were treated with clomipramine and eleven received
      fluoxetine. The dextromethorphan metabolic ratio (MR) median was significantly
      higher in the fluoxetine group (0.255) than in the clomipramine group (0.083, p <
      0.014). In this study, fluoxetine involved a greater decrease of CYP2D6 metabolic
      capacity than clomipramine. Clinical implications and the possible connection
      between a decreased CYP2D6 activity and adverse drug effects were discussed.
      Caution should be taken when drugs with a low therapeutic index must be
      coprescribed in such patients.

PMID- 15252822
TI  - Subjective and polysomnographic effects of milnacipran on sleep in depressed
      patients.
AB  - The effects of milnacipran (50 mg bid) on sleep patterns of eight depressed
      inpatients, treated for 4 weeks, were studied during the initial (days 1-3) and
      terminal (days 26-28) treatment periods and compared with those obtained from
      three sleep recordings performed just prior to the initiation of the treatment.
      The clinical evolution of patients was evaluated weekly using the MADRS
      depression scale and the Spiegel and Norris sleep scales. Clinical improvement,
      shown by a mean reduction of 58% in MADRS scale scores, was accompanied by an
      improvement of disturbed sleep parameters. From the beginning of treatment, there
      was an increase in the total duration of sleep and stage II sleep, a decrease in
      sleep latency and an increase in sleep efficiency. Total REM sleep was not
      modified although, since there was an increase in total sleep time, the percent
      REM sleep was significantly reduced. REM latency was increased early in the
      study, an effect classically associated with antidepressant treatment. This study
      suggests that milnacipran improves disturbed sleep parameters in depressed
      patients without any additional disturbance at the onset of treatment.

PMID- 15252823
TI  - Comparative efficacy of newer hypnotic drugs for the short-term management of
      insomnia: a systematic review and meta-analysis.
AB  - OBJECTIVES: To compare the clinical effectiveness of zaleplon, zolpidem or
      zopiclone (Z-drugs) with either benzodiazepines licensed and approved for use in
      the UK for the short-term management of insomnia (diazepam, loprazolam,
      lorazepam, lormetazepam, nitrazepam, temazepam) or with each other. METHODS:
      MEDLINE, EMBASE, PsycINFO, Science Citation Index/Web of Science were searched
      from 1966 to March 2003 and The Cochrane Library, reference lists of included
      studies and a number of psychopharmacology journals. Randomized controlled trials
      comparing either benzodiazepines with the Z-drugs or any two of the Z-drugs in
      patients with insomnia were included. Outcome measures included: sleep onset
      latency, total sleep duration, number of awakenings, quality of sleep, adverse
      events, tolerance, rebound insomnia and daytime alertness. RESULTS AND
      CONCLUSIONS: Twenty four eligible studies were identified with a total study
      population of 3,909 (17 studies comparing a Z-drug with a benzodiazepine and 7
      comparing a Z-drug). Insufficient or inappropriately reported data meant that
      meta-analysis was possible only for a small number of outcomes. There are few
      clear, consistent differences between the drugs. Some evidence suggests that
      zaleplon gives shorter sleep latency but shorter duration of sleep than zolpidem,
      reflecting the pharmacological profiles of the drugs.

PMID- 15252824
TI  - Effects of modafinil on cognitive and meta-cognitive performance.
AB  - The stimulant modafinil has proved to be an effective treatment modality for
      narcolepsy and related sleep disorders and is also being studied for use during
      sustained military operations to ameliorate the effects of fatigue due to sleep
      loss. However, a previous study reported that a relatively large, single dose of
      modafinil (300 mg), administered to already sleep-deprived individuals, caused
      participants to overestimate their cognitive abilities (i.e. 'overconfidence').
      Because the predominant application of modafinil is in otherwise healthy, non
      sleep-deprived individuals, the present study investigated the generality of
      modafinil-induced overconfidence in a group of 18 healthy, non sleep-deprived
      adults. The design involved a double-blind, placebo controlled, fully within
      subjects manipulation of placebo and modafinil (4 mg/kg: approximately 300 mg, on
      average) over three 50-min cognitive testing sessions (i.e. before drug
      ingestion, and at 90 and 180 min after drug ingestion). The cognitive task
      battery included subjective assessments of mood, fatigue, affect, vigor and
      motivation, and cognitive assessments of serial reaction time, logical reasoning,
      visual comparison, mental addition and vigilance. In addition, trial-by-trial
      confidence judgements were obtained for two of the cognitive tasks and more
      global, task level assessments of performance were obtained for four of the
      cognitive tasks. Relative to placebo, modafinil improved fatigue levels,
      motivation, reaction time and vigilance. In terms of self-assessments of
      cognitive performance, both the placebo and modafinil conditions were 'well
      calibrated' on trial-by-trial confidence judgements, showing neither marked over-
      nor under-confidence. Of note, the modafinil condition displayed a non
      significant tendency towards 'overconfidence' for task-level assessments of
      performance. The present findings highlight the need for continued research on
      the many complex interactions involving fatigue states, occasional versus long
      term stimulant use, and subjective assessments of fatigue and cognitive
      performance.

PMID- 15252825
TI  - Effects of dietary caffeine on mood when rested and sleep restricted.
AB  - Prolonged use of caffeine can lead to physical dependence evidenced by
      characteristic withdrawal symptoms during abstinence. Debate exists as to whether
      mood enhancement by caffeine represents a net effect or merely the restoration of
      abstinence-induced mood decrements. One aim of this study was to determine the
      net effects on mood of dietary caffeine compared with prolonged abstinence. In
      addition, the study aimed to determine whether caffeine restores mood degraded by
      a non-caffeine source, namely, sleep restriction. A double-blind placebo
      controlled cross-over design was employed in which 48 male and female volunteers
      alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times
      daily for 4 consecutive weeks, while being either rested or sleep restricted.
      Mood was assessed using a computerized version of the profile of mood states
      (POMS), giving scores for overall mood and six mood dimensions. Gender had small
      effects on mood, whereas all mood dimensions were markedly adversely affected by
      sleep restriction. Caffeine had no significant net enhancing effects on mood when
      participants were rested, and produced no net restorative effects when mood was
      degraded by sleep restriction. On the contrary, caffeine-induced decrements in
      mood were observed during both conditions of rest and sleep restriction.

PMID- 15252826
TI  - Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a
      double blind cross-over study.
AB  - Increasing evidence suggests that the cholinergic system is involved in the
      pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor,
      improves psychotic symptomatology in demented patients, however, evidence for its
      role in the management of active psychosis in schizophrenia remains limited. An
      18-week double blind cross-over study was conducted in which eight patients were
      randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10
      mg/day for the following 4 weeks) or placebo as augmentation treatment to
      clozapine. After this initial phase, there was a 2-week washout period of the
      study medication after which the same regimen was crossed over at the same dose
      and for the same period (8 weeks). No significant difference was noted in the
      total positive and negative symptom scale scores when donepezil was compared with
      placebo (16.7%+12.97% vs 3.20%+13.94% respectively, p = 0.18). However, three
      patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%)
      during the donepezil treatment phase, while only one patient improved (20.87%)
      during the placebo phase. No differences were noted in the Calgary depression
      scale (p = 0.305), Simpson Angus scale (p = 0.374), clinical global impression
      improvement scale (p = 0.23) and clinical global impression-severity of illness
      scores (p = 0.116). Although this preliminary study failed to demonstrate a clear
      effect of donepezil augmentation in clozapine treated chronic schizophrenia
      patients, it seems that the subtle positive effect of donepezil observed in some
      of our patients should encourage further investigation in a larger sample of this
      patient subpopulation.

PMID- 15252827
TI  - Mechanism of inhibitory effect of citalopram on isolated guinea-pig atria in
      relation to adenosine receptor.
AB  - The effect of citalopram (CTP), a selective serotonin reuptake inhibitor
      antidepressant was studied on the rate and force of contractions of isolated
      guinea-pig atria. CTP (2-32 microg/ml) caused a dose-dependent decrease in the
      contractile force (7%-62%) and in the rate of contractions (11%-72%). These
      negative inotropic and chronotropic effects of CTP (8 microg/ml) were not
      prevented by atropine (1 microg/ml) and 3,7 dimethyl-1-propargylxanthine (DMPX;
      1.5 microg/ml), an adenosine A(2) receptor antagonist, but 1,3 dipropargyl-8
      cyclopentylxanthine (DPCPX; 12 microg/ml), a specific adenosine A(1) receptor
      antagonist significantly blocked these effects (p < 0.001) and theophylline (30
      microg/ml) a non-selective adenosine A(1)/A(2A) receptor antagonist also
      prevented the inotropic and chronotropic effects of CTP. These results suggest
      that the negative inotropic and chronotropic effect of CTP on isolated guinea-pig
      atria is probably mediated through an inhibition of the uptake of adenosine or
      the A(1) receptor mechanism.

PMID- 15252828
TI  - Paroxetine treatment of delusional disorder, somatic type.
AB  - A 77-year-old female showed delusion of infestation in the oral cavity. She was
      treated by paroxetine 20 mg/day, and the hypochondriacal delusion disappeared
      after 8 weeks. Hypoperfusion in the left temporal and parietal lobes which was
      observed when she had the delusion was normalized after resolution of the
      delusion. This report suggests that paroxetine may be effective for delusional
      disorder, somatic type. It also supports the previous views that this disorder is
      associated with serotonergic dysfunction and hypoperfusion in the temporal and
      parietal lobes.

PMID- 15252829
TI  - Possible serotonin syndrome arising from an interaction between caffeine and
      serotonergic antidepressants.

PMID- 15252830
TI  - Levetiracetam in bipolar spectrum disorders: first evidence of efficacy in an
      open, add- on study.

PMID- 15252831
TI  - A case of temporo-mandibular disorder with fibromyalgia treated with the
      antidepressant, milnacipran.

PMID- 15252832
TI  - Outdoor air pollution and lung cancer: recent epidemiologic evidence.

PMID- 15252833
TI  - IL-6 as an intracrine growth factor for renal carcinoma cell lines.
AB  - Interleukin-6 (IL-6) is produced at high levels by renal cell carcinoma cell
      lines. The molecular mechanisms involved in its possible role as an autocrine
      growth factor were investigated. IL-6 and IL-6 receptor expression was
      investigated in 8 renal cell carcinoma (RCC) cell lines. The modulation of RCC
      cell line proliferation by an anti-IL-6 Ab, an IL-6 antisense oligonucleotide
      (ASON) directed against the second exon of IL-6 and cytokines inhibiting IL-6
      production (IL-4 and IL-13) was investigated. All 8 RCC cell lines expressed IL-6
      mRNA, produced IL-6 and expressed the soluble and membrane-bound gp130 chain of
      IL-6 receptor. The gp80 chain of IL-6 receptor was undetectable at the surface of
      the 8 RCC cell lines tested, while the soluble form of gp80 was detectable in the
      supernatant of one of these cell lines. The addition of a blocking IL-6 Ab did
      not inhibit the proliferation of any of the 8 RCC cell lines. In contrast, IL-6
      ASON inhibited specifically IL-6 production and the proliferation of all RCC cell
      lines. Exogenous IL-6 failed to restore RCC cell line proliferation blocked by
      ASON, indicating that IL-6 acts through an intracrine loop in RCC cell lines. IL
      13 and IL-4 inhibited the proliferation of 7 of the 8 cell lines without
      interfering with IL-6 or IL-6 receptor expression. IL-6 ASON inhibited the
      proliferation of the 8 RCC cell lines tested additively with IL-4 or IL-13. IL-6
      is an intracrine growth factor in renal cell carcinoma cell lines.

PMID- 15252834
TI  - Implications of cytokeratin 8/18 filament formation in stratified epithelial
      cells: induction of transformed phenotype.
AB  - The cytokeratin (CK) pair 8 and 18 is normally expressed in all simple epithelia.
      This pair is not normally seen in stratified epithelial cells. Squamous cell
      carcinomas derived from stratified epithelia show anomalous expression of this CK
      pair. It is not known whether CKs 8 and 18 in any way contribute to the malignant
      phenotype of these cells. We used an immortalised, nontransformed human foetal
      buccal mucosa (FBM) cell line that expresses significantly higher amounts of CK18
      compared to CK8. FBM cells were transfected with the full-length CK8 gene to
      study the role of CKs 8 and 18 in malignant transformation. Clones with higher
      expression of CK8 compared to untransfected FBM cells were studied for changes in
      their phenotypic characteristics. Immunofluorescence studies using antibodies to
      CKs 8 and 18 revealed well-decorated filaments throughout the cytoplasm in CK8
      gene-transfected cells vs. untransfected FBM cells. Transmission images showed
      that FBM cells were isolated while transfected cells were in groups of well
      spread cells with cellular projections. Transfected cells were independent of
      growth supplement requirements and showed anchorage-independent growth in soft
      agar assay and significantly reduced doubling time compared to nontransfected FBM
      cells. DNA flow-cytometric studies revealed increased DNA content and prolonged S
      phase in transfected clones vs. FBM cells. Injection of cells s.c. obtained from
      soft agar colonies developed from 2 of the clones resulted in tumour formation at
      the site of injection. In both cases, lung metastasis was also seen. Thus, in
      conclusion, it appears that increased expression of CK8 in some way changes the
      phenotypic characteristics of stratified epithelial cells, resulting in malignant
      transformation.

PMID- 15252835
TI  - DNA binding sites for putative methylation boundaries in the unmethylated region
      of the BRCA1 promoter.
AB  - Changes in DNA methylation patterns are frequently observed in human cancers and
      are associated with a decrease in tumor suppressor gene expression.
      Hypermethylation of the BRCA1 promoter has been reported in a portion of sporadic
      breast tumours that correspond to a reduction in BRCA1 transcription and
      expression. Questions remain concerning the maintenance of methylation free zones
      in promoter regions of tumor suppressor genes in normal tissues. Sodium bisulfite
      based analysis of the BRCA1 promoter defines a methylation free zone in normal
      breast tissue that starts 650 bp upstream of the transcription start site and
      extends for 1.4 kb through most of the BRCA1 CpG island. We provide data
      implicating 2 proteins, Sp1 and CTCF, in the maintenance of this methylation-free
      zone. Both of these proteins have been shown to function as methylation
      boundaries in other genes. Four Sp1 sites have been identified in the BRCA1
      promoter by gel shift assays. In vivo binding of Sp1 has been confirmed at 2 of
      these sites in the BRCA1 promoter and at 2 CTCF sites that flank the unmethylated
      region. Our data suggest that these DNA binding sites for Sp1 and CTCF may act as
      boundary elements that are important in maintaining genomic integrity by
      delineating the normal methylation free BRCA1 promoter. Inactivation or
      disruption of these boundaries may facilitate an epigenetic "hit", in this case
      DNA methylation, leading to BRCA1 downregulation and contributing to
      tumorigenesis, particularly the genesis of sporadic breast tumours.

PMID- 15252836
TI  - Inhibition of growth and survival of human head and neck squamous cell carcinoma
      cells by curcumin via modulation of nuclear factor-kappaB signaling.
AB  - Increased expression of proinflammatory and proangiogenic factors are associated
      with aggressive tumor growth and decreased survival of patients with head and
      neck squamous cell carcinoma (HNSCC). In as much as genes that are regulated by
      nuclear factor NF-kappaB suppress apoptosis, induce proliferation, and mediate
      inflammation, angiogenesis and tumor metastasis, agents that suppress NF-kappaB
      activation have potential as treatment for various cancers including HNSCC. We
      demonstrate that all HNSCC cell lines expressed constitutively active NF-kappaB
      and IkappaBalpha kinase (IKK), which is needed for NF-kappaB activation.
      Treatment of MDA 686LN cells with curcumin (diferuloylmethane), a
      pharmacologically safe chemopreventive agent, inhibited NF-kappaB activation
      through abrogation of IKK. As a result expression of various cell survival and
      cell proliferative genes including Bcl-2, cyclin D1, IL-6, COX-2 and MMP-9 was
      suppressed. This, in turn, inhibits proliferation of all HNSCC cell lines,
      arrests cell cycle in G1/S phase (MDA 686LN) and induces apoptosis as indicated
      by upstream and downstream caspase activation, PARP cleavage, annexin V staining
      in MDA 686LN cells. Suppression of NF-kappaB by cell-permeable p65-based peptide
      and NBD peptide also inhibited the proliferation and induced apoptosis in these
      cells. Our results indicate that curcumin is a potent inhibitor of cell
      proliferation and an inducer of apoptosis in HNSCC through suppression of IKK
      mediated NF-kappaB activation and of NF-kappaB-regulated gene expression.

PMID- 15252837
TI  - Breast cancer metastatic potential: correlation with increased heterotypic gap
      junctional intercellular communication between breast cancer cells and
      osteoblastic cells.
AB  - The breast cancer metastasis-suppressor gene BRMS1 is downregulated in metastatic
      breast cancer cells. Previous reports have shown restoration of gap junctional
      intercellular communication (GJIC) in the metastatic human breast carcinoma cell
      line MDA-MB-435 (435) transfected with BRMS1 cDNA. Metastasis, to a large extent
      in most breast cancers, occurs to bone. However, the reason for this preferential
      metastasis is not known. We explored cell-to-cell communication between 435
      carcinoma cells and a human osteoblastic cell line, hFOB1.19, to determine
      whether carcinoma cells can form gap junctions with bone cells and to explore the
      role of these heterotypic gap junctions and the BRMS1 gene in breast cancer
      metastasis to bone. 435 cells displayed greater cell-to-cell communication with
      hFOB 1.19 cells than with themselves. Transfection of BRMS1 into 435 cells
      increased homotypic gap junctional communication but did not significantly affect
      heterotypic communication with hFOBs. However, heterotypic communication of BRMS1
      transfectants with hFOB cells was reduced relative to homotypic communication. In
      contrast, parental 435 cells displayed greater heterotypic communication with
      hFOBs relative to homotypic communication. Our results suggest that there are
      differences in the relative homotypic and heterotypic GJIC of metastasis-capable
      and -suppressed cell lines.

PMID- 15252838
TI  - Gene transfer to cervical cancer with fiber-modified adenoviruses.
AB  - Successful adenoviral (Ad) vector-mediated strategies for cancer gene therapy
      mandate gene-delivery systems that are capable of achieving efficient gene
      delivery in vivo. In many cancer types, in vivo gene-transfer efficiency remains
      limited due to the low or highly variable expression of the primary Ad receptor,
      the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of
      CAR on cervical cancer cells as well as CAR-independent targeting strategies to
      integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both
      (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and
      primary cervical cancer cells isolated from patients to quantify the expression
      of CAR mRNA and to evaluate the gene-transfer efficiency of fiber-modified Ads.
      Of the fiber-modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly
      enhanced gene-transfer efficiency in vitro. Gene-delivery efficiency in vivo was
      evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly
      improves tumor targeting in vivo, resulting in a significantly improved
      tumor/liver ratio in mice. Our results suggest that the double-modified
      Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer
      substrates, while the infectivity of nontarget cells in the mouse is not
      increased and comparable to Ad5. The fiber-modified virus described here can help
      achieve higher clinical efficacy of cervical cancer gene therapy.

PMID- 15252839
TI  - High BRAF mutation frequency does not characterize all melanocytic tumor types.
AB  - Cutaneous melanoma (CM) is the most lethal form of skin cancer. Along with some
      benign melanocytic tumors, the majority shows BRAF or NRAS mutation, but it is
      not known whether these are essential to all forms of melanocytic neoplasia. We
      screened 79 melanocytic tumors of different types for BRAF and NRAS mutations and
      looked at MAPK pathway activity using immunohistochemistry in a subset.
      Significant differences in BRAF exon 15 mutation frequency were found: 14/16
      (87.5%) in common acquired naevi (CANs), 9/12 (75%) in CMs, 0/26 in Spitz naevi
      and 3/25 (12%) in blue naevi (p < 0.01). We looked at whether Spitz and blue
      naevi showed a compensatory increase in BRAF exon 11 and/or NRAS exons 1 and 2
      mutations to account for the low BRAF exon 15 mutation frequency. NRAS mutations
      were found in only 1/16 (6.3%) Spitz naevi and 0/15 blue naevi. In addition, NRAS
      mutations were found in 2/11 (18.2%) CANs and 3/12 (25%) CMs. None of the tumors
      showed BRAF exon 11 mutations. Despite their low combined BRAF and NRAS mutation
      frequency, Spitz naevi showed strong MAPK pathway activation as measured by
      cytoplasmic expression of dually phosphorylated ERK1/2, while blue naevi had weak
      pathway activation. We conclude that BRAF and NRAS mutations are not necessary
      for melanocytic tumor development and that some types of tumor must arise by
      alternative mechanisms.

PMID- 15252840
TI  - Neoexpression of N-cadherin in E-cadherin positive colon cancers.
AB  - In our study, we aimed to investigate the expression of N-cadherin and E-cadherin
      and their dependency on epithelial-mesenchymal transition regulators SNAI1, SIP1
      and TWIST in human colon cancer. Expression of E-cadherin and N-cadherin was
      examined by immunohistochemistry in 80 colon carcinomas by using paraffin
      embedded and formalin fixed tissues. Those cases were partly analyzed for mRNA
      expression of N-cadherin (42 cases), TWIST (18 cases), SNAI1 (25 cases) and SIP1
      (25 cases) by real-time quantitative RT-PCR. Additionally, colon carcinomas that
      showed amplification of 20q13, the localization of the human SNAI1 gene, were
      examined. We found cytoplasmic and/or membrane-associated immunoreactivity of N
      cadherin in 35/80 (44%) of the cases. However, there was no correlation to
      upregulated TWIST mRNA levels, as we have shown previously for diffuse-type
      gastric cancers with abnormal N-cadherin expression. Reduced and/or cytoplasmic E
      cadherin immunoreactivity was detected in 19% (15/80) of the cases. Expression of
      SNAI1 or SIP1 mRNA was not seen in any of the 25 cases analyzed. There was no
      correlation between amplification of 20q13 and SNAI1 mRNA expression. Remarkably,
      N-cadherin was almost exclusively expressed in those cases showing normal E
      cadherin immunoreactivity, suggesting a mutual exclusion between abnormal E
      cadherin reduction and upregulation of N-cadherin. For the first time, we
      postulate a role for N-cadherin in primary colon cancer progression, which may be
      similar to the effect discovered by others in breast cancer cell lines, where
      coexpressed N-cadherin can exert a dominant function over E-cadherin's adhesive
      function and thus promote tumor invasiveness.

PMID- 15252841
TI  - Non-self-discrimination as a driving concept in the identification of an
      immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma
      cancer patients.
AB  - We analyzed the sera of patients with melanoma to define the human humoral
      autoantibody profile towards HMW-MAA. Computational proteome scanning using the
      non-self-discrimination principle as a guide led to the individuation of the low
      similarity HMW-MAA781-789RATVWMLRL peptide fragment as an immunodominant B-cell
      epitope. Linear B-cell determinant individuation was experimentally validated by
      dot blot immunoassay and NMR spectroscopy analysis. Regulation of physiologic
      self-reactivity by the non-self-discrimination principle is discussed.

PMID- 15252842
TI  - Increased expression of amyloid precursor protein in oral squamous cell
      carcinoma.
AB  - In our previous study, we identified amyloid precursor protein (APP) in an oral
      squamous cell carcinoma (OSCC)-enriching subtractive hybridization library. Our
      present study attempts to define the significance of APP expression in the
      genesis of OSCC. RT-PCR analysis showed increase in APP mRNA expression for more
      than 2-fold in 76% of OSCC (n = 55) relative to corresponding non-cancerous
      matched tissues (NCMT). The majority of esophageal SCCs also had increase in APP
      mRNA expression. OSCC patients exhibiting increase in APP mRNA expression had
      significantly lower survival rate compared to patients exhibiting the opposite
      status. Western blotting analysis identified APP751 and APP770 as the major APP
      isoforms in oral keratinocytes. A high correlation between mRNA and protein
      expressions of APP was noted in OSCC/NCMT pairs. Immunohistochemistry further
      showed a remarkable increase of APP in OSCC tissue relative to NCMT. Treatment
      with an antisense oligonucleotide against APP reduced cellular and secreted APP
      as well as growth in an OSCC cell line. Our study provides novel clues that APP
      expression is involved in the proliferation and carcinogenesis of OSCC.
      Correlated with such pathogenesis was the survival of its victims. The degree of
      APP expression could serve as an invaluable marker for oral carcinogenesis.

PMID- 15252843
TI  - Clinical relevance of amphiregulin and VEGF in primary breast cancers.
AB  - The characterization of novel prognostic markers in breast cancer is necessary to
      improve the identification of high-risk populations. In our study, the prognostic
      significance of VEGF and amphiregulin (AR) was investigated and compared to
      conventional prognostic factors in primary breast cancers. The analysis was
      performed using enzyme-linked immuno-assay in a series of 193 patients, and
      univariate and multivariate analysis were performed in the overall population as
      well as in pre- and post-menopausal patients subdivided in node-negative (N-) and
      node-positive (N+) subsets. AR (median, 44.8 pg/mg protein) appeared strongly
      correlated with progesterone receptors (PgR) (p = 0.0018) in the premenopausal N+
      population, and with uPA (p= 0.020) and VEGF (p= 0.0053) in the postmenopausal/N+
      patients. Despite these attractive data, AR expression was not significant for
      recurrence or survival outcome. Data revealed strong correlation between VEGF and
      uPA, and PAI-1, in the N+ population. Moreover, patients with high VEGF levels
      displayed poor outcome, with an increased risk for N+ subset. These data were
      confirmed by multivariate analysis that presented histologic grade (HR, 10.55, p
      = 0.001) and VEGF (HR, 3.89, p = 0.03) as the prominent prognostic markers for
      overall survival for the N+ population. Furthermore, infiltrating ductal
      carcinomas (IDC) were shown to express higher levels of both uPA (p < 0.0001) and
      VEGF (p = 0.002) than intralobular carcinomas. This retrospective study
      reinforces the pejorative biological role of VEGF in the progression of breast
      tumors. Our data also suggest that VEGF and uPA might play particular role in the
      biology and progression of IDC.

PMID- 15252844
TI  - Molecular detection of circulating tumor cells is an independent prognostic
      factor in patients with high-risk cutaneous melanoma.
AB  - Detection of circulating tumor cells (CTCs) might improve current staging
      procedures by identifying a subgroup of patients with minimal residual disease
      and thus a higher risk of disease recurrence. Forty patients with > or =2-mm
      thick cutaneous melanoma with or without lymph node metastasis were enrolled.
      After standard radical surgery and adjuvant therapy in case of lymph node
      metastasis, patients were followed up with routine physical and radiologic
      assessments as well as serial PCR-based analysis of CTCs using 2 melanoma markers
      (tyrosinase and Melan-A/Mart-1). After a median follow-up of 30 months, 18
      patients had disease recurrence and 28 were PCR-positive before the disease
      became clinically evident. The sensitivity of the molecular test was 83%. Median
      time to PCR positivity and median PCR-to-relapse time were 12 and 8 months,
      respectively. At multivariate analysis, PCR positivity was an independent
      predictor of disease recurrence (hazard ratio=2.06, 95% CI 1.07-3.35; p=0.03).
      Among high-risk melanoma patients, serial PCR-based analysis of CTCs can identify
      a subgroup at higher risk of disease recurrence, with clinically significant
      advance. Therefore, CTC detection might be employed for the selection of patients
      for adjuvant treatment and during follow-up for early indication of therapeutic
      failure.

PMID- 15252845
TI  - Amount of DNA in plasma and cancer risk: a prospective study.
AB  - Levels of plasma DNA concentrations in cancer patients have been shown to be
      higher than the plasma DNA concentrations found in healthy subjects. The value of
      plasma DNA levels for development of neoplastic or pulmonary disease was
      evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed
      from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx,
      larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease
      (COPD), including never smokers and ex-smokers, from 9 countries across Europe.
      The amount of plasma DNA was variable across the European Prospective
      Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations
      in some centers might be due to the type of population recruited and/or the
      treatment of the samples. An elevated and statistically significant odds ratio
      (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while
      nonsignificant increased ORs were present for oral cancers, cancers of the
      pharynx and larynx and leukemia. When the analyses were stratified by time since
      recruitment (below or above 36 months), the increased ORs were limited to the
      more recent period of recruitment, i.e., a time elapsed between blood drawing and
      disease onset lower than 36 months. This was particularly true for COPD deaths
      (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67).

PMID- 15252846
TI  - Dietary calcium, vitamin D, VDR genotypes and colorectal cancer.
AB  - The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer
      either independently or in conjunction with calcium and vitamin D intake. We
      evaluate the association between calcium, vitamin D, dairy products, and VDR
      polymorphisms in 2 case-control studies of colon and rectal cancer (n = 2,306
      cases and 2,749 controls). Dietary intake was evaluated using a detailed diet
      history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1
      polymorphism and a 3' untranslated region poly-A length polymorphism (designated
      S for short and L for long). The SS genotype reduced risk of colorectal cancer
      for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55-0.92). High
      levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95%
      CI = 0.24-0.64) but were not associated with rectal cancer in men (OR = 1.02; 95%
      CI = 0.66-1.56). Similar reduced rectal cancer risk among women was observed at
      high levels of vitamin D (OR = 0.52; 95% CI = 0.32-0.85) and low-fat dairy
      products (OR = 0.61; 95% CI = 0.39-0.94). High levels of sunshine exposure
      reduced risk of rectal cancer among those diagnosed when <60 years of age (OR =
      0.62, 95% CI = 0.42-0.93). Examination of calcium in conjunction with VDR
      genotype showed that a significant 40% reduction in risk of rectal cancer was
      observed for the SS or BB VDR genotypes when calcium intake was low (p
      interaction = 0.01 for calcium interaction). For colon cancer, high levels of
      dietary intake of calcium, vitamin D, and low-fat dairy products reduced risk of
      cancer for the SS or BB VDR genotypes, although the p for interaction was not
      statistically significant. These data support previous observations that high
      levels of calcium and vitamin D reduce risk of rectal cancer and provide support
      for a weak protective effect for the SS and BB VDR genotypes. The risk associated
      with VDR genotype seems to depend upon the level of dietary calcium and vitamin D
      and tumor site.

PMID- 15252847
TI  - Aerodigestive and gastrointestinal tract cancers and exposure to crocidolite
      (blue asbestos): incidence and mortality among former crocidolite workers.
AB  - The objective of this article was to assess the association between the incidence
      and mortality from aerodigestive cancers and exposure to crocidolite (blue
      asbestos). Our study is a cohort study of former workers of the now-defunct
      crocidolite mining and milling operation at Wittenoom, Western Australia, who
      have been followed up since 1979 and on whom asbestos exposure and smoking
      information was known. Standardised mortality and incidence rates were used to
      compare former workers with the Western Australian male population. Cases were
      matched with up to 10 randomly assigned controls, and conditional logistic
      regression was used to examine the relationship between asbestos exposure,
      smoking status and cancer incidence. There were 129 incident cases from all
      cancers of interest and 57 deaths. Former workers had a significantly higher risk
      of mortality from upper aerodigestive cancers than the Western Australian male
      population. The incidence of upper and lower aerodigestive cancers was higher in
      the Wittenoom cohort but not significantly so. Cumulative exposure to asbestos
      did not appear to be associated with the incidence of stomach cancer, colorectal
      cancer or upper aerodigestive cancers. Smoking status was strongly associated
      with the incidence of upper aerodigestive cancers, with current smokers
      experiencing the greatest risk. Our study with longer and more complete follow
      up, smoking information and a stronger study design does not show an association
      between cumulative asbestos exposure and stomach cancer or other gastrointestinal
      cancers. The excess mortality from upper aerodigestive cancers seen in this
      cohort of former asbestos workers compared to the Western Australian male
      population does not appear to be associated with exposure to crocidolite.

PMID- 15252848
TI  - Body size and breast cancer risk: findings from the European Prospective
      Investigation into Cancer And Nutrition (EPIC).
AB  - The evidence for anthropometric factors influencing breast cancer risk is
      accumulating, but uncertainties remain concerning the role of fat distribution
      and potential effect modifiers. We used data from 73,542 premenopausal and
      103,344 postmenopausal women from 9 European countries, taking part in the EPIC
      study. RRs from Cox regression models were calculated, using measured height,
      weight, BMI and waist and hip circumferences; categorized by cohort-wide
      quintiles; and expressed as continuous variables, adjusted for study center, age
      and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive
      breast cancers were identified. In postmenopausal women, current HRT modified the
      body size-breast cancer association. Among nonusers, weight, BMI and hip
      circumference were positively associated with breast cancer risk (all ptrend < or
      = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI
      < 25. Among HRT users, body measures were inversely but nonsignificantly
      associated with breast cancer. Excess breast cancer risk with HRT was
      particularly evident among lean women. Pooled RRs per height increment of 5 cm
      were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in
      postmenopausal women. Among premenopausal women, hip circumference was the only
      other measure significantly related to breast cancer (ptrend = 0.03), after
      accounting for BMI. In postmenopausal women not taking exogenous hormones,
      general obesity is a significant predictor of breast cancer, while abdominal fat
      assessed as waist-hip ratio or waist circumference was not related to excess risk
      when adjusted for BMI. Among premenopausal women, weight and BMI showed
      nonsignificant inverse associations with breast cancer.

PMID- 15252849
TI  - Childbirth and breast cancer prognosis.
AB  - Although certain risk factors for breast cancer incidence may also effect
      survival, findings have been inconsistent and the long-term role of childbirth is
      unknown. We studied the influence of number and timing of births on breast cancer
      prognosis prospectively. From 1958 to 1997, altogether 32,003 women, born 1932 or
      later, were notified to the Swedish Cancer Registry due to a primary invasive
      breast cancer. We obtained information on dates of all childbirths and achieved
      complete follow-up through 1997 by means of linkage to other nation-wide
      databases. Proportional hazards analyses were used to compute crude and
      multivariate hazard ratios (HR) with 95% confidence intervals (CI) of dying from
      breast cancer. We found a successively worse prognosis for women with a shorter
      delay between their last birth and breast cancer diagnosis (p for trend <0.0001).
      Compared to women with their last birth more than 10 years before diagnosis, the
      multivariate HR of breast cancer death was 1.39 (95% CI 1.17-1.67) for those with
      breast cancer diagnosis in the 3rd year after last birth and 1.72 (CI 95% 1.42
      2.09) for those with diagnosis within 1 year after last birth. This adverse
      effect on prognosis of childbirth persisted beyond 10 years among women with a
      first birth before the age of 20 years. A pregnancy has marked adverse effects on
      the prognosis of a breast cancer diagnosed within 10 years after delivery. These
      findings suggest that pregnancy influences tumor biology.

PMID- 15252850
TI  - Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of
      IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial
      glioma.
AB  - Interferon-beta (IFN-beta) has been used as an antitumor drug against human
      glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a
      new gene therapy using the IFN-beta gene against malignant gliomas and then began
      clinical trials in 2000. Since stimulation of immune system was one mechanism of
      antitumor effect induced by IFN-beta gene therapy, we hypothesized that
      combination of IFN-beta gene therapy with immunotherapy might increase its
      effectiveness. In the present study, we tested whether combination therapy with
      IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic
      cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an
      experimental mouse intracranial glioma (GL261), which cannot be cured by either
      IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following
      DC immunotherapy resulted in a significant prolongation in survival of the mice.
      Moreover, when this combination was performed twice, 50% of treated mice survived
      longer than 100 days. Considering these results, this combination therapy may be
      one promising candidate for glioma therapy in the near future.

PMID- 15252851
TI  - Comparison of 10 serum bone turnover markers in prostate carcinoma patients with
      bone metastatic spread: diagnostic and prognostic implications.
AB  - Our aim was to assess the diagnostic accuracy of bone markers in serum of
      patients with prostate cancer (PCa) for early detection of bone metastases and
      their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa
      patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35
      patients with benign prostatic hyperplasia, bone formation markers [total and
      bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen
      propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers
      [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N
      terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid
      phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin
      (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured.
      tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa
      patients with bone metastases compared to patients without metastases. OPG showed
      the best discriminatory power to differentiate between these patients. Logistic
      regression analysis resulted in a model with OPG and TRAP as variables that
      predicted bone metastasis with an overall correct classification of 93%. Patients
      with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut
      off levels showed significantly shorter survival than patients with low marker
      concentrations. Multivariate Cox proportional hazards regression revealed that
      only OPG and BSP were independent prognostic factors for PCa-related death. Thus,
      the importance of serum OPG in detecting bone metastatic spread, alone or in
      combination with other bone markers, and predicting survival in PCa patients has
      been clearly demonstrated.

PMID- 15252852
TI  - Association between female breast cancer and cutaneous melanoma.
AB  - Epidemiologic studies have provided suggestive evidence of a link between
      cutaneous melanoma (CM) and breast cancer (BC). Moreover, carriers of mutations
      in the breast cancer predisposition gene, BRCA2, have an increased risk of
      melanoma while carriers of mutations in the melanoma susceptibility gene, CDKN2A,
      exhibit a higher than expected risk of breast cancer. These findings raise the
      possibility that pathways involved in the development of CM and BC overlap and
      that survivors of one cancer may be prone to develop the other. To this end, we
      set out to determine if survivors of female BC in the Surveillance, Epidemiology
      and End Result (SEER) database are at increased risk for CM and vice versa. We
      followed female BC patients registered in the 1973-1999 SEER database for
      development of a second CM and female CM patients for the development of a second
      BC. The expected number of cases was then compared to the observed number of
      cases using standardized incidence ratios. Overall, we found a modest but
      statistically significant increased risk of CM among female BC survivors and vice
      versa. Among young BC patients, we observed a 46% elevated risk of a second CM.
      Women who underwent radiation therapy exhibited a 42% increased risk for CM. The
      risks of BC among female CM survivors and CM among BC survivors were also
      elevated, albeit to a much lesser degree (overall, 11% and 16%, respectively). We
      found a mutual association between female BC and CM. The elevated risk for CM,
      especially among younger BC patients, suggests that the genetic observations from
      high-risk groups may also be operative at a much lower level in the general BC
      population.

PMID- 15252853
TI  - Possible association between HPV16 E7 protein level and cytokeratin 19.
AB  - The mechanisms employed by human papillomaviruses (HPVs) to control the
      replication of the viral genome and the expression of the viral genes are
      extremely complex and further complicated by the fact that the viral life cycle
      is intricately tied to the differentiation program of its host epithelial tissue.
      Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal
      cytokeratin (CK) expression pattern progress pari passu during the stepwise
      process that preludes to squamous cell carcinoma. In our study, we have analyzed
      the interaction occurring between HPV type 16 E7 mRNA and the intermediate
      cytokeratin filaments 7 and 19 and report data in favor of a possible association
      between HPV16 E7 protein level and CK19.

PMID- 15252854
TI  - Extensive analysis of the 7q31 region in human prostate tumors supports TES as
      the best candidate tumor suppressor gene.
AB  - Loss of heterozygosity (LOH) on chromosome arm 7q31 is found in many prostate
      tumors. Such alterations are generally associated with inactivation of tumor
      suppressor genes. It has been shown previously that the main region of LOH at
      7q31 spans the interval between the D7S486 and D7S2460 microsatellite loci, which
      contains several candidate tumor suppressor genes (TSG) such as TES, CAV2, CAV1,
      MET, CAPZA2, ST7 and WNT2. We tested 41 human sporadic prostate tumors for 7q31
      LOH by using 5 polymorphic markers overlapping the critical region and used a
      real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay to study
      the expression of the 7 candidate TSGs located in this genomic region. We found
      that CAV1, CAV2, MET and TES mRNA expression was lower in prostate tumors than in
      normal prostate tissues. Our immunohistochemical results and previously published
      data on the compartmental expression of these messenger RNAs in stromal and
      epithelial cells suggest that TES is the best candidate tumor suppressor gene at
      7q31.

PMID- 15252855
TI  - Association of DNA repair gene XRCC1 polymorphisms with head and neck cancer in
      Korean population.
AB  - Squamous cell carcinoma of the head and neck (SCCHN), which is relatively
      prevalent in Korea, is believed to be induced by environmental carcinogens and
      host genetic factors. Accumulating evidence has shown that genetic differences in
      DNA repair capacity resulting from genetic polymorphism influence the risk of
      environmental carcinogenesis. We therefore examined the associations of genetic
      polymorphisms in the DNA repair genes XRCC1 with the risk of SCCHN in a Korean
      population (hospital-based, case-control study; 147 cases and 168 controls).
      Three known polymorphisms in the XRCC1 gene were genotyped: R194W(C>T) in exon 6,
      R280H(G>A) in exon 9 and R399G(G>A) in exon 10. Although no significant
      associations were apparent with R280H(G>A) and R399G(G>A), a highly significant
      association (p = 0.0005) of R194W(C>T) with the increased risk (OR = 2.61; 95% CI
      1.53-4.46) of SCCHN was detected among patients and normal controls under
      dominant model. The frequency of minor allele-containing genotypes (TT and CT)
      was much higher in SCCHN patients (51.8%) compared to that in normal controls
      (30.3%) (p = 0. 0005). When considering a relatively small number of cases (n =
      147) and controls (n = 168) in our study, larger studies are needed to validate
      the genetic effects of XRCC1 polymorphisms in Asian populations. In conclusion,
      the result from our study provides additional evidence of an association of the
      XRCC1 polymorphism (Arg194Trp) with SCCHN as markers of genetic susceptibility in
      the Korean population.

PMID- 15252856
TI  - Familial risk for colon and rectal cancers.

PMID- 15252858
TI  - Atelinae phylogenetic relationships: the trichotomy revived?
AB  - This research examines phylogenetic relationships between members of the Atelinae
      subfamily (Alouatta, Ateles, Brachyteles, and Lagothrix), based on analysis of
      three genetic regions. Two loci, cytochrome c oxidase subunit II (COII) and the
      hypervariable I portion of the control region, are part of the mitochondrial
      genome. The other is a single-copy nuclear gene, Aldolase A Intron V. Analysis of
      these genetic regions provides support for tribe Alouattini containing the
      Alouatta species, while tribe Atelini contains the other three genera. However,
      these three genetic regions produce conflicting results for relationships among
      tribe Atelini members. Previous genetic studies supported grouping Brachyteles
      with Lagothrix, leaving Ateles in a separate subclade. The present data sets vary
      based on the genetic region analyzed and method of analysis suggesting all
      possible cladistic relationships. These results are more consistent with
      investigations of morphology and behavior among these primates. The primary cause
      of discrepancy between this study and previous genetic studies is postulated to
      reside in increased sampling in the present study of genetic variation among
      members of the Atelinae, specifically Ateles. The present study utilized samples
      of Ateles from all postulated species for this genetically variable primate,
      while previous studies used only one or two species of Ateles. This paper
      demonstrates that shifting relationships are produced when different species of
      Ateles are used to reconstruct phylogenies. This research concludes that a
      trichotomy should still be supported between members of tribe Atelini until
      further analyses, which include additional Atelinae haplotypes are conducted.

PMID- 15252859
TI  - Functional anatomy of the olecranon process in hominoids and plio-pleistocene
      hominins.
AB  - This study examines the functional morphology of the olecranon process in
      hominoids and fossil hominins. The length of the bony lever of the triceps
      brachii muscle (TBM) is measured as the distance between the trochlear articular
      center and the most distant insertion site of the TBM, and olecranon orientation
      is measured as the angle that this bony lever makes with the long axis of the
      ulna. Results show that Homo, Pan, Gorilla, most monkeys, and the
      Australopithecus fossils studied have similar relative olecranon lengths.
      Suspensory hominoids and Ateles have shorter olecranons, suggesting, in some
      instances, selection for greater speed in extension. The orientation that the
      lever arm of the TBM makes with the long axis of the ulna varies with preferred
      locomotor mode. Terrestrial primates have olecranons that are more posteriorly
      oriented as body size increases, fitting general models of terrestrial mammalian
      posture. Arboreal quadrupeds have more proximally oriented lever arms than any
      terrestrial quadrupeds, which suggests use of the TBM with the elbow in a more
      flexed position. Olecranon orientation is not consistent in suspensory hominoids,
      although they are all characterized by orientations that are either similar or
      more posterior than those observed in quadrupeds. Homo and the fossils have
      olecranons that are clearly more proximally oriented than expected for a
      quadruped of their size. This suggests that Homo and Australopithecus used their
      TBM in a flexed position, a position most consistent with manipulatory
      activities.

PMID- 15252860
TI  - Has the transition to agriculture reshaped the demographic structure of
      prehistoric populations? New evidence from the Levant.
AB  - This paper presents the demographic changes that followed the transition from a
      hunting-gathering way of life (Natufian) to an agricultural, food-producing
      economy (Neolithic) in the southern Levant. The study is based on 217 Natufian
      (10,500-8,300 BC) skeletons and 262 Neolithic (8,300-5,500 BC) skeletons. Age and
      sex identification were carried out, and life tables were constructed. A five
      parameter competing hazard model developed by Siler ([1979] Ecology 60:750-757)
      was used to smooth life-table data. No indication of increased mortality with the
      advent of agriculture was noted. On the contrary, both life expectancy at birth
      (24.6 vs. 25.5 years) and adults' mean age at death (31.2 vs. 32.1 years)
      increased slightly from the Natufian to the Neolithic period (assuming stationary
      populations). Yet the transition to agriculture affected males and females
      differently: mean age at death in the Natufian was higher for adult females
      compared to adult males, while in the Neolithic, it was the reverse. One
      interpretation given to the distribution of female ages at death is that with the
      onset of the Neolithic period, maternal mortality increased as a result of a
      concomitant increase in fertility. If the adoption of agriculture in the Levant
      increased the rate of population growth at the beginning of the Neolithic,
      expectation of life may have increased dramatically.

PMID- 15252861
TI  - Reconstructing relationships among mortality, status, and gender at the Medieval
      Gilbertine Priory of St. Andrew, Fishergate, York.
AB  - The varied relationships among status, gender, and mortality are complex,
      historically produced phenomena that shape people's lives and deaths in socially
      meaningful ways. Paleodemographic analysis coupled with acute sensitivity to site
      specific context has the potential to move us toward a greater understanding of
      these experiences in the past. After considering the potential effects of
      migration and fertility on the age-at-death profiles of adult individuals
      interred at the Gilbertine Priory of St. Andrew, Fishergate, York (n = 200), it
      is asserted that these profiles primarily reveal expected and unexpected
      relationships among status, gender, and mortality in this Medieval context.
      Collectively, the long lives of religious-status males compared to other
      composite and gendered status groups suggest that they experienced a relatively
      comfortable existence despite periodic complaints of destitution. The postulated
      demographic advantage of high-status males did not materialize in the analysis,
      and a reevaluation of the skeletal evidence indicates that nearly 20% of these
      individuals died violently. Unexpectedly, moderate-status females shared a
      mortality profile similar to that of religious-status males and retained a
      demographic advantage over all other secular status groups. In contrast to the
      experiences of moderate-status females, low-status females had, on average, the
      shortest lives at St. Andrew's. This pattern is intimately linked to their
      restriction from crucial social and economic resources, and provides further
      evidence of their marginalization in York's wage-labor economy. Overall, these
      relationships suggest that traditional, highly stratified and gendered notions of
      Medieval status and mortality are not adequate for understanding the intricacies
      of everyday life and death at St. Andrew's.

PMID- 15252862
TI  - Relationship of strain magnitude to morphological variation in the primate skull.
AB  - In a comparative study of variation in primate skulls, Wood and Lieberman ([2001]
      Am. J. Phys. Anthropol. 116:13-25) proposed that a predictable relationship
      exists between in vivo bone-strain magnitudes and the extent of morphological
      variation in skeletal structures. They hypothesized that regions subject to high
      strains are prone to enhanced levels of variation. Three questions are posed with
      respect to the plausibility of this hypothesis. First, does the proposed
      relationship hold at different levels of analysis (e.g., for more restricted
      anatomical regions in which large strain gradients are present)? Second, is the
      biomechanical rationale for the hypothesis sound, given the current understanding
      of bone biology? Third, is the hypothesis obviated by consideration of the
      functional matrix concept of skull development, in which osseous growth is
      posited to be governed by surrounding soft tissues (e.g., muscle and tendon) and
      developing spaces (e.g., the nasal capsule)? The different perspectives explored
      by these questions suggest that the validity of the hypothesis, despite having a
      defensible theoretical rationale, is likely to be context-specific. A direct role
      for strain magnitude in conditioning morphological variation is difficult to
      demonstrate either comparatively or theoretically, and it is unlikely that a
      single strain threshold or interval can be directly associated with elevated
      variation in the skeleton. The conceptual framework of the functional matrix
      (which allows for independent growth among different regions of the skull)
      conceivably contravenes the premise of a uniform relationship of strain magnitude
      to morphological variability.

PMID- 15252863
TI  - Circadian rhythms in diet and habitat use in red ruffed lemurs (Varecia rubra)
      and white-fronted brown lemurs (Eulemur fulvus albifrons).
AB  - Daily variation in niche use among vertebrates is attributed to a variety of
      factors, including thermoregulatory, reproductive, and nutritional requirements.
      Lemuriform primates exhibit many behavioral and physiological adaptations related
      to thermoregulation and sharp, seasonal reproduction, yet they have rarely been
      subjects of a quantitative analysis of circadian (or daily) rhythms in niche use.
      In this study, I document daily rhythms in diet and microhabitat use over an
      annual cycle in two sympatric, frugivorous lemurs, Varecia rubra and Eulemur
      fulvus albifrons. Data on diet, forest site, and forest height were recorded at 5
      min time points on focal animals and divided into three time blocks for analysis
      (06:00-10:00 hr, 10:00-14:00 hr, and 14:00-18:00 hr). I employed multivariate
      tests of independence to examine daily rhythms in diet and microhabitat use
      according to sex, season, and reproductive stage. Throughout the day, V. rubra is
      frugivorous and dwells in the upper canopy, with notable departures (especially
      for females) during the hot seasons, gestation, and lactation. E. f. albifrons
      has heterogeneous daily rhythms of food choice and microhabitat use, particularly
      across seasons, and both sexes are equally variable. These daily rhythms in diet
      and microhabitat use appear related to thermoregulatory and nutritional
      requirements, seasonal food availability and circadian rhythms of plant (and
      possibly insect) palatability, predator avoidance tactics, and in the case of
      Varecia, to reproduction. Daily rhythms of food choice in V. rubra support two
      previously suggested hypotheses explaining why primates consume more nonfruit
      items late in the day, whereas those of E. f. albifrons are too variable to lend
      support to these hypotheses.

PMID- 15252864
TI  - Population genetics of apolipoproteins A-IV, E, and H, and the angiotensin
      converting enzyme (ACE): associations with lipids, and apolipoprotein levels in
      American Samoans.
AB  - Distributions of alleles at three apolipoprotein loci (APO E, APO H, and APO A
      IV) and an insertion/deletion (I/D) polymorphism at the angiotensin converting
      enzyme (ACE) locus among 274 American Samoans are described here. Genotypes at
      each locus are examined for associations with quantitative lipid (total
      cholesterol (total-c), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), and
      triglycerides) and apolipoprotein (APO AI, APO AII, APO E, and APO B) levels.
      Genotype frequencies at all four loci are in Hardy-Weinberg equilibrium. The most
      common APO A-IV genotype (1-1) was observed in 252 American Samoans (97%). The
      three most common APO E genotypes were 3-3 (47%), 3-4 (30%), and 2-3 (12%). The
      most frequent APO H genotype was 2-2 (86%). The most common ACE genotype (I/I)
      was observed in 75% of sampled individuals, and 23% were I/D heterozygotes. APO E
      genotypic variation was associated with total-c, HDL-c, LDL-c, and all four
      quantitative apolipoproteins (AI, AII, E, and B). APO A-IV genotypes were
      associated significantly with total cholesterol, LDL-c, and APO-B levels. APO H
      showed little association with any quantitative lipid or apolipoprotein. ACE D/D
      homozygotes had higher AII levels. ACE showed a consistent association with APO
      AII levels, with either APO A-IV or APO E as a covariate. The interaction term
      between ACE and APO E was also significantly associated with total-c and APO E
      levels, and the ACE genotype showed a significant main effect on APO AI levels in
      multivariate analyses.

PMID- 15252865
TI  - Genetic signatures of pre-expansion bottleneck in the Choctaw population of
      Oklahoma.
AB  - Previous research showed that the Choctaw Indians of Oklahoma exhibit
      considerable linkage disequilibria (LD) in a number of regions of the genome that
      has allowed genetic fine mapping for potential susceptibility genes for the
      autoimmune connective tissue disease scleroderma, or systemic sclerosis (SSc). In
      principle, such enhanced background LD in the Choctaws could be caused by
      population bottleneck event(s) followed by recent population expansion. This
      investigation utilizes genome-scan data on 175 dinucleotide loci from 76 Choctaw
      individuals to seek genetic evidence of the demographic history of the Choctaw
      Nation. Of the 175 loci examined, 105 are in Hardy-Weinberg equilibrium. The
      average unbiased homozygosity over the 105 loci for the Choctaws (29.3%) is
      significantly higher than that in the European descent group (20.9%); and when
      adjusted for sample-size differences, the Choctaw also exhibit a significantly
      smaller number of segregating alleles (6.65 vs. 8.14) at these loci. Both of
      these observations are consistent with the trend expected in an isolated
      population. Comparison of the allele size variance and gene diversity yields an
      imbalance index (lnbeta) of 0.811 in the Choctaw. Of the 105 loci examined, 93
      exhibit excess expected homozygosity in comparison to the expectations of a
      stepwise mutation model in a population of constant size. Taken together, these
      observations are consistent with a signature of the recent population size
      expansion of the Choctaws, preceded by bottleneck event(s).

PMID- 15252866
TI  - Global changes in the expression patterns of RNA isolated from the hippocampus
      and cortex of VX exposed mice.
AB  - One of the established activities of the nerve agent VX is inhibition of the
      enzyme acetylcholinesterase (AChE). This inhibition affects the cholinergic
      nervous system by decreasing the activity of the neurotransmitter-hydrolyzing
      enzyme cholinesterase (ChE). In an effort to gain a more comprehensive
      understanding of the molecular pathways affected by low-level exposure to VX, an
      expression profiling approach was used to identify genes with altered RNA
      expression patterns after exposure.Specifically, mice were exposed to 0.1, 0.2,
      0.4, and 0.6 LD50 VX for a period of 2 weeks. At 2 h, 72 h, and 2 weeks after the
      final exposure, RNA was isolated from both the hippocampus and the cortex.
      Changes in gene expression levels were assessed by DNA microarray technology and
      grouped according to their expression patterns. Data presented here demonstrate
      that 2 weeks postexposure all up-regulated gene expression has returned to pre
      exposure levels, including genes related to the central nervous system.
      Additionally, this investigation has revealed non-AChE pathway genes involved in
      other neuronal functions that display altered expression profiles after VX
      exposure.

PMID- 15252867
TI  - Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2:
      absence of a phenobarbital-responsive enhancer module in the upstream region of
      the CYP2B18 gene.
AB  - Potential mechanisms were investigated whereby CYP2B18, a cytochrome P450 gene
      exhibiting high constitutive expression but only low levels of phenobarbital
      inducibility in the guinea pig liver, may be differentially regulated versus the
      highly inducible rat CYP2B2 gene. To comparatively assess potential regulatory
      sequences associated with CYP2B18, a guinea pig genomic library was screened
      enabling isolation of the CYP2B18 gene. The genomic screening process resulted in
      the identification of at least four closely-related CYP2B18 genes, designated
      here as CYP2B18A-D. Of these isolates, CYP2B18A exhibited sequence identical to
      that of the CYP2B18 cDNA. Further, the deduced amino acid sequence of the CYP2B18
      cDNA was identical to that of N-terminal and internally-derived peptide sequences
      obtained in this investigation from CYP2B18 protein isolated from guinea pig
      liver. Genomic structural sequences were derived for CYP2B18A, together with the
      respective 5'-upstream and intronic regions of the gene. Comparison of the
      CYP2B18A and CYP2B2 gene sequences revealed the lack of repetitive LINE gene
      sequences in CYP2B18A, putative silencing elements that effect neighboring genes,
      although these sequences were present in both 5'-upstream and 3'-downstream
      regions of CYP2B2. We determined that the phenobarbital-responsive enhancer
      module was absent from the 5'-upstream region as well as the intronic regions of
      CYP2B18A gene. We hypothesize that the compromised phenobarbital inducibility of
      CYP2B18A stems from its lack of a functional phenobarbital responsive enhancer
      module.

PMID- 15252868
TI  - Regulation of CYP1A2 by histone deacetylase inhibitors in mouse hepatocytes.
AB  - Cytochrome P450 1A2 (CYP1A2) is constitutively expressed in the mouse liver, but
      the constitutive expression progressively declines to an undetectable level in
      isolated hepatocytes. In this study, CYP1A2 was induced in hepatocytes exposed to
      the histone deacetylase inhibitors trichostatin A (TSA) and sodium butyrate (SB),
      but only well after constitutive CYP1A2 expression was silenced. However,
      cotreatment with the arylhydrocarbon receptor (AhR) ligand 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and either TSA or SB reduced the induction of
      CYP1A2 with the same time course as TSA or SB increased its induction. These
      results suggest that histone modification is involved in CYP1A2 regulation in
      hepatocytes through pathways that are independent of AhR.

PMID- 15252869
TI  - Characterization of Cd-induced molecular events prior to cellular damage in
      primary rat hepatocytes in culture: activation of the stress activated signal
      protein JNK and transcription factor AP-1.
AB  - The effect of Cadmium (Cd) on the expression of c-Jun N-terminal kinase (JNK), c
      jun, and activator protein-1 (AP-1) has been investigated. We previously reported
      that Cd causes cell damage as indicated by increases in the cytotoxic parameters,
      lactate dehydrogenase and lipid peroxidation, and this damage was mediated by
      decreases in cellular concentration of glutathione. In the present study, we
      investigate the molecular events involved prior to the Cd-induced cellular
      toxicity and damage in primary rat hepatocytes. We propose that Cd, through the
      generation of reactive oxygen species (ROS) and prior to significant cellular
      damage, activates the stress activated signal protein JNK, regulates c-jun
      expression, and promotes the binding of a redox sensitive transcription factor AP
      1. We show JNK activity and c-jun mRNA level significantly increased at 1 h and
      AP-1 DNA binding activity significantly enhanced at 3 h in the presence of 4
      microM cadmium chloride. Blocking the Cd induction of JNK activity, c-jun mRNA
      level, and AP-1 binding activity using the antioxidants N-acetyl cysteine (10 mM)
      or carnosol (0.5 microg/mL) suggests a role for ROS. Blocking JNK activity and c
      jun mRNA by SP600125 (20 microM), a JNK inhibitor, supports the role of JNK in
      transmission of signals induced by Cd.

PMID- 15252870
TI  - Mechanistic studies on protopanaxadiol, Rh2, and ginseng (Panax quinquefolius)
      extract induced cytotoxicity in intestinal Caco-2 cells.
AB  - Certain ginsenosides, also known as triterpene glycosides, have been recently
      reported to have a characteristic effect on cultured intestinal and leukemia cell
      growth. Ginsenoside aglycones 20(S)-protopanaxadiol (PD), 20(S)-protopanaxatriol
      (PT), and ginsenoside Rh2 have been identified as having a strong effect on
      reducing cell viability. Furthermore, ginsenoside Rh2 is thought to be a rare
      ginsenoside not found in all ginseng products. Rather, Rh2 has been recently
      reported to be a breakdown product of thermal processing of North American
      ginseng. In this study, pure ginsenosides PD, PT, Rh2 standards and an enriched
      Rh2 fraction derived from ginseng leaf were tested in cultured Caco-2 cells for
      relative cytotoxic potency. PD and Rh2 LC50 were similar after 24 to 72 h,
      whereas a drop in PT LC50 occurred later at 48 and 72 h. Furthermore, PD and Rh2
      affected membrane integrity as indicated by LDH secretion earlier than PT and the
      enriched Rh2 fraction (P < or = 0.05). Ginsenoside Rh2 showed the greatest (P <
      or = 0.05) build up of necrotic cells (18.3 +/- 0.1%) at the respective LC50
      after 24 h and PD (21.3 +/- 0.3%) showed the largest effect after 44 h of
      exposure. The effect on apoptotic cells at 44 h of treatment were significantly
      different (P < or = 0.05) for Rh2 (21 +/- 0.4%), PD (14.6 +/- 0.1%), enriched Rh2
      leaf fraction (9.9 +/- 0.6%), and PT (2.3 +/- 0.1%) treatments. Caco-2 caspase-3
      activity was different between ginsenoside exposure; Rh2 (10.6 +/- 0.3 nM pNA)
      had the greatest (P < or = 0.05) activity followed by the enriched Rh2 leaf
      fraction (8.3 +/- 0.2 nM pNA), PT (7.3 +/- 0.3 nM pNA). The PD (4.8 +/- 0.04 nM
      pNA) treatment was similar to untreated cells (4.3 +/- 0.05 nM pNA) in caspase-3
      activity. These results show variable bioactive response in cultured intestinal
      cell to specific ginsenosides and an enriched Rh2 North American ginseng extract
      which may be explained on basis of hydrophobic/hydrophilic balance.

PMID- 15252871
TI  - Evidence of hair loss after subacute exposure to 2-chloroethyl ethyl sulfide, a
      mustard analog, and beneficial effects of N-acetyl cysteine.
AB  - Mustard gas has been used as a vesicant chemical warfare agent. However, a
      suitable biomarker for monitoring mustard gas exposure is not known. We observed
      that the hairs of the guinea pigs exposed intratracheally to subacute doses of 2
      chloroethyl ethyl sulfide (CEES), a mustard analog, came out very easily though
      there was no sign of skin lesions or skin damage. Also the hairs looked rough and
      dry and lost the shiny glaze. There was no recovery from this hair loss, though
      the animals never became hairless, following CEES exposure. Hairs were observed
      in this study both visually and with light microscopy. Treatment with N
      acetylcysteine (NAC) prior to CEES exposure could prevent the hair loss
      completely. Hence, sudden hair loss might be a good biomarker for subacute
      exposure of mustard gas to subjects at risks when the victims might have no other
      visible symptom of toxicity.

PMID- 15252872
TI  - p-Aminophenol-induced hepatotoxicity in hamsters: role of glutathione.
AB  - p-Aminophenol (PAP) is a widely used industrial chemical and a known nephrotoxin.
      Recently, it was found to also cause hepatotoxicity and glutathione (GSH)
      depletion in mice. The exact mechanism of liver toxicity is not known. The aims
      of this study were to determine whether PAP can cause acute hepatotoxicity in
      hamsters and to further investigate the role of GSH in PAP-induced toxicity. PAP
      was administered ip to hamsters in doses of 200-800 mg/kg. Liver damage at 24 h
      after PAP administration was assessed by elevations in plasma enzyme activities
      and histopathologic examination. GSH and cysteine (Cys) levels in liver at 4 h
      were determined by HPLC. PAP decreased hepatic GSH concentration to 8% and Cys to
      30% of vehicle control values. It increased plasma glutamic pyruvic transaminase
      (GPT) activity by 47-fold and sorbitol dehydrogenase (SDH) activity by 113-fold.
      PAP also caused severe centrilobular hepatocellular necrosis. 2(RS)-n
      Propylthiazolidine-4(R)-carboxylic acid (PTCA), a Cys precursor, attenuated the
      PAP-induced decreases in hepatic sulfhydryl levels; GSH and Cys were 39% and 78%
      of vehicle controls, respectively. PTCA also attenuated the PAP-induced
      elevations in plasma enzyme activities and hepatic necrosis. It was concluded
      that PAP hepatotoxicity is associated with depletion of hepatic GSH and can be
      prevented by PTCA.

PMID- 15252876
TI  - The structure and function of auditory chordotonal organs in insects.
AB  - Insects are capable of detecting a broad range of acoustic signals transmitted
      through air, water, or solids. Auditory sensory organs are morphologically
      diverse with respect to their body location, accessory structures, and number of
      sensilla, but remarkably uniform in that most are innervated by chordotonal
      organs. Chordotonal organs are structurally complex Type I mechanoreceptors that
      are distributed throughout the insect body and function to detect a wide range of
      mechanical stimuli, from gross motor movements to air-borne sounds. At present,
      little is known about how chordotonal organs in general function to convert
      mechanical stimuli to nerve impulses, and our limited understanding of this
      process represents one of the major challenges to the study of insect auditory
      systems today. This report reviews the literature on chordotonal organs
      innervating insect ears, with the broad intention of uncovering some common
      structural specializations of peripheral auditory systems, and identifying new
      avenues for research. A general overview of chordotonal organ ultrastructure is
      presented, followed by a summary of the current theories on mechanical coupling
      and transduction in monodynal, mononematic, Type 1 scolopidia, which
      characteristically innervate insect ears. Auditory organs of different insect
      taxa are reviewed, focusing primarily on tympanal organs, and with some
      consideration to Johnston's and subgenual organs. It is widely accepted that
      insect hearing organs evolved from pre-existing proprioceptive chordotonal
      organs. In addition to certain non-neural adaptations for hearing, such as
      tracheal expansion and cuticular thinning, the chordotonal organs themselves may
      have intrinsic specializations for sound reception and transduction, and these
      are discussed. In the future, an integrated approach, using traditional
      anatomical and physiological techniques in combination with new methodologies in
      immunohistochemistry, genetics, and biophysics, will assist in refining
      hypotheses on how chordotonal organs function, and, ultimately, lead to new
      insights into the peripheral mechanisms underlying hearing in insects.

PMID- 15252873
TI  - Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on
      membrane ion permeability.
AB  - The interference of glibenclamide, an antidiabetic sulfonylurea, with
      mitochondrial bioenergetics was assessed on mitochondrial ion fluxes (H+, K+, and
      Cl-) by passive osmotic swelling of rat liver mitochondria in K-acetate, KNO3,
      and KCl media, by O2 consumption, and by mitochondrial transmembrane potential
      (Deltapsi). Glibenclamide did not permeabilize the inner mitochondrial membrane
      to H+, but induced permeabilization to Cl- by opening the inner mitochondrial
      anion channel (IMAC). Cl- influx induced by glibenclamide facilitates K+ entry
      into mitochondria, thus promoting a net Cl-/K+ cotransport, Deltapsi dissipation,
      and stimulation of state 4 respiration rate. It was concluded that glibenclamide
      interferes with mitochondrial bioenergetics of rat liver by permeabilizing the
      inner mitochondrial membrane to Cl- and promoting a net Cl-/K+ cotransport inside
      mitochondria, without significant changes on membrane permeabilization to H+.

PMID- 15252877
TI  - The physiology of insect auditory afferents.
AB  - This review presents an overview of the physiology of primary receptors serving
      tympanal hearing in insects. Auditory receptor responses vary with frequency,
      intensity, and temporal characteristics of sound stimuli. Various insect species
      exploit each of these parameters to differing degrees in the neural coding of
      auditory information, depending on the nature of the relevant stimuli. Frequency
      analysis depends on selective tuning in individual auditory receptors. In those
      insect groups that have individually tuned receptors, differences in physiology
      are correlated with structural differences among receptors and with the
      anatomical arrangement of receptors within the ear. Intensity coding is through
      the rate-level characteristics of tonically active auditory receptors and through
      variation in the absolute sensitivities of individual receptors (range
      fractionation). Temporal features of acoustic stimuli may be copied directly in
      the timing of afferent responses. Salient signal characteristics may also be
      represented by variation in the timing of afferent responses on a finer temporal
      scale, or by the synchrony of responses across a population of receptors.

PMID- 15252878
TI  - Processing of auditory information in insects.
AB  - Insects exhibit an astonishing diversity in the design of their ears and the
      subsequent processing of information within their auditory pathways. The aim of
      this review is to summarize and compare the present concepts of auditory
      processing by relating behavioral performance to known neuronal mechanisms. We
      focus on three general aspects, that is frequency, directional, and temporal
      processing. The first part compares the capacity (in some insects high) for
      frequency analysis in the ear with the rather low specificity of tuning in
      interneurons by looking at Q10dB values and frequency dependent inhibition of
      interneurons. Since sharpening of frequency does not seem to be the prime task of
      a set of differently tuned receptors, alternative hypotheses are discussed.
      Moreover, the physiological correspondence between tonotopic projections of
      receptors and dendritic organization of interneurons is not in all cases strong.
      The second part is concerned with directional hearing and thus with the ability
      for angular resolution of insects. The present concepts, as derived from
      behavioral performances, for angular resolution versus lateralization and serial
      versus parallel processing of directional and pattern information can be traced
      to the thoracic level of neuronal processing. Contralateral inhibition, a
      mechanism for enhancing directional tuning, appears to be most effective in
      parallel pathways, whereas in serial processing it may have detrimental effects
      on pattern processing. The third part, after some considerations of signal
      analysis in the temporal domain, demonstrates that closely related species often
      use different combinations of temporal parameters in their recognition systems.
      On the thoracic level, analysis of temporal modulation functions and effects of
      inhibition on spiking patterns reveals relatively simple processing, whereas
      brain neurons may exhibit more complex properties.

PMID- 15252879
TI  - Psychophysics in insect hearing.
AB  - Psychophysics has much to offer the study of insect hearing. Not only is there a
      rich set of experimental methods to apply, there is a large body of experimental
      work on vertebrate hearing that can suggest topics for investigation and provide
      material for cross-species comparisons. We present an overview of the methods of
      psychophysics, followed by specific examples of their use in insects. Topics
      covered include intensity discrimination, frequency analysis and discrimination,
      temporal integration and acuity, and localization. We conclude by pointing out
      additional areas of research suggested by the reviewed work and areas in which a
      psychophysical approach would be useful.

PMID- 15252881
TI  - Limit cycles, noise, and chaos in hearing.
AB  - Based on insight obtained from a newly developed cochlea model, we argue that
      noise-driven limit cycles are the basic ingredient in the mammalian cochlea
      hearing process. For insect audition, we provide evidence in favor of the
      persistence of this principle. We emphasize the role of bifurcations for the
      emergence of broad-range sound perception, both in the frequency and amplitude
      domain, and indicate that this crucially depends on the correct coupling between
      limit cycles. We review the limit-cycle coupling universality, and outline how it
      can be used to encode information. Cortical noise is the microscopic basis for
      this encoding, whereas chaos emerges as the macroscopic expression of computation
      being done in the network. Large neuron firing variability is one possible
      consequence of the proposed mechanism that may apply to both vertebrate and
      insect hearing.

PMID- 15252880
TI  - Anatomical and molecular design of the Drosophila antenna as a flagellar auditory
      organ.
AB  - The molecular basis of hearing is less well understood than many other senses.
      However, recent studies in Drosophila have provided some important steps towards
      a molecular understanding of hearing. In this report, we summarize these findings
      and their implications on the relationship between hearing and touch. In
      Drosophila, hearing is accomplished by Johnston's Organ, a chordotonal organ
      containing over 150 scolopidia within the second antennal segment. We will
      discuss anatomical features of the antenna and how they contribute to the
      function of this flagellar auditory receptor. The effects of several mutants,
      identified through mutagenesis screens or as homologues of vertebrate auditory
      genes, will be summarized. Based on evidence gathered from these studies, we
      propose a speculative model for how the chordotonal organ might function.

PMID- 15252882
TI  - [Folate against hyperhomocysteinemia. A new approach for the prevention and
      therapy of alcoholism-associated disorders?].
AB  - There is growing evidence that chronic alcoholism is associated with a
      derangement in the sulfur amino acid metabolism. Excitatory aminoacids such as
      glutamate, aspartate, and homocysteine have been shown to be increased in
      patients with chronic alcoholism who underwent alcohol withdrawal. Furthermore,
      sustained hyperhomocysteinemia occurred in chronic alcoholics with active
      drinking pattern. Excitotoxicity can be induced by increased hormocysteine levels
      via rebound activation of NMDA receptor-mediated glutamatergic neurotransmission
      upon the removal of ethanol-evoked inhibition. Therefore, hyperhomocysteinemia
      may be responsible for the higher incidence of complications during alcohol
      withdrawal (e.g.stroke,convulsions). In addition, an association between brain
      atrophy and increased levels of homocysteine in chronic alcoholism was shown.
      This may have important implications for the pathogenesis of brain atrophy in
      alcoholics. Taking into account that high plasma homocysteine levels are helpful
      in the prediction of alcohol withdrawal seizures, early anti-convulsive therapy
      could prevent this severe complication. Supplementation of folate, a cofactor of
      the homocysteine metabolism, lowers raised homocysteine levels and therefore
      could be established as a new therapeutic strategy in alcohol withdrawal
      treatment. The results of various studies highlight the need for further research
      to prove whether alcoholics benefit from a reduced homocysteine level with
      respect to both, alcohol-related disorders and alcohol withdrawal symptoms.

PMID- 15252883
TI  - [The importance of sleep for healthy alcohol consumers and alcohol dependent
      patients].
AB  - This article deals with the effects of alcohol on sleep and sleep EEG of healthy
      individuals and alcohol-dependent patients during different phases of alcohol
      dependency. Healthy individuals initially experience an improvement in sleep,
      although a greater quantity of alcohol can lead to problems of sleep maintenance
      during the second half of the night. Pre-existing sleep deprivation or sleep
      restriction potentiates the effects of alcohol. Alcohol-dependent patients are
      found to be more prone to sleep problems than healthy individuals, which can
      facilitate the development of alcoholism. These patients experience difficulty
      falling asleep and suffer from a reduced total sleep time during all phases of
      the disorder, often accompanied by other sleep disorders such as sleep apnea
      syndrome or periodic leg movements during sleep. Certain predictors for the risk
      of relapse in abstinent alcoholics have been identified. Neurobiological findings
      in sleep and alcohol dependency are discussed. The cholinergic-aminergic
      reciprocal interaction model of REM and non-REM sleep regulation is significant
      in this context. Therapeutic implications are discussed.

PMID- 15252884
TI  - [Diabetes mellitus as a complication of treatment with atypical neuroleptics.
      Possible pathomechanisms and treatment recommendations].
AB  - An increased risk for occurrence of diabetic metabolic states has been reported
      for treatment with atypical antipsychotics. Initial studies suggest that atypical
      antipsychotics as a heterogeneous group of substances are not equally concerned.
      An increased risk for development of diabetes mellitus can be assumed for
      clozapine and olanzapine, while other atypical and conventional antipsychotics
      seem to carry only a slightly elevated risk. It remains as yet unresolved whether
      there is a causal connection or whether other not yet identified factors are
      involved. However, atypical antipsychotics intervene in various ways in glucose
      and fatty acid metabolism due to their broad receptor profile. We suggest that
      some atypical antipsychotics disturb regulatory loops of fat metabolism in fatty
      tissue and muscle,which may result in insulin resistance and finally diabetes.
      Changes in leptin release and development of leptin resistance possibly play an
      important role. These new results should be considered when planning therapy,
      although a final risk analysis is not yet possible.

PMID- 15252885
TI  - [Diagnostic and clinical aspects of complex post-traumatic stress disorder].
AB  - The symptomatology of patients suffering in the aftermath of severe and prolonged
      traumatization is not entirely covered by the diagnostic criteria of post
      traumatic stress disorder (PTSD). Consequently, the concept of complex PTSD was
      proposed, including symptoms of affective dysregulation, dissociation and
      somatization, alterations in self-perception, altered relationships with others,
      and altered systems of meaning. Thereby, a variety of symptoms usually classified
      as co-morbid disorders are combined in a single etiological model. The whole
      symptomatology is considered as more or less effective adaptation strategies and
      not primarily as deficits. This understand-ing of the underlying etiology in
      subjects with complex traumatization opens perspectives for new psychotherapeutic
      treatment strategies which have already shown effectiveness in daily practice.

PMID- 15252886
TI  - [Comparative study of life quality in patients with cycloid and schizophrenic
      psychoses].
AB  - BACKGROUND: Cycloid psychoses represent a nosological entity not adequately
      recognised by contemporary psychiatry. They show full recovery after each episode
      and thus have a favourable prognosis. METHODS: Course, psychiatric status, social
      function, and quality of life (QoL) of 33 patients with cycloid psychosis and 44
      schizophrenics were compared (CGI, PANSS, GAF, Strauss-Carpenter,WHOQOL
      BREF).Also, 48 controls were asked to rate their QoL. RESULTS: The schizophrenics
      developed symptoms earlier in life (P=0.009) and were hospitalized longer
      (P=0.001) and more frequently(P=0.01) than patients with cycloid psychosis. The
      latter showed better scores in the applied scales (P<0.0001). In QoL measures,
      cycloid psychotic patients were more satisfied than schizophrenic patients in
      three of four domains(P<0.01). Only in one domain did they differ from controls
      (P<0.01). CONCLUSION: Cycloid psychoses display better course, outcome, and QoL
      than schizophrenia.Thus, they appear to present a useful concept deserving more
      clinical and scientific attention.

PMID- 15252887
TI  - [Resources in schizophrenic patients. Validity testing of a new rating scale to
      assess health features].
AB  - Biopsychosocial concepts and Antonovsky's salutogenesis model gave rise to new
      treatment approaches and research prospects in health-related fields. Also in
      psychiatry, there is increasing interest to obtain information on patients'
      resources. There are, nevertheless, only a few instruments developed particularly
      for this assessment. The new EGA rating scale offers the possibility to assess
      patient resources as abilities and health-maintaining features in four areas of
      life. To test the validity of the EGA, 39 schizophrenic patients participated in
      the current study. Those with more health-maintaining features in the EGA showed
      significantly fewer psychic and somatic symptoms (SCL-90 R), better social and
      occupational functioning (SOFAS), higher sense of coherence (SOC), and better
      social adjustment(FSI). They were significantly younger at the beginning of their
      disease and had more frequently held jobs during the previous 12 months. The
      findings point to satisfactory concept- and criterion-related validity and
      reliability of the EGA rating scale as well as to its possible application in
      course studies, individual diagnosis, therapy evaluation, and indication. Early
      medical and therapeutic intervention and increased use of working aid programs
      are recommended.

PMID- 15252888
TI  - [Expectations and satisfaction from relatives of psychiatric patients in
      inpatient treatment].
AB  - Based upon a content analysis of interviews(n=32), a questionnaire evaluating
      expectations and satisfaction with psychiatric inpatient care was developed and
      sent to all caregivers whose ill family members gave their agreement to the
      survey (n=1 39). The response rate was 41.7% (n=58). Successful treatment of the
      patient by competent physicians and psychologists, understandable and sincere
      explanations to caregivers regarding the patient's disease, support of the
      patient's self-confidence and gains in confidence, psychotherapy for the patient,
      and by no means psychopharmacological treatment were assessed as most important
      by caregivers. From their point of view, gaps between expectations and
      satisfaction with inpatient care exist, especially regard-ing the following
      aspects: patient psychotherapy, information to caregivers about therapies,
      medication, side effects and treatment progress, understandable and sincere
      explanation to care-givers, support in dealing with the patients, and information
      about the possibilities of rehabilitation after inpatient care.

PMID- 15252889
TI  - [Peripartum psychiatric disorders--support through men? A first approach].
AB  - We investigated the partners of 27 women with pre- or postpartal psychiatric
      disorders. All women were treated as inpatients at a mother-child unit after
      delivery. The men's behaviour as partners and fathers was rated in a categorical
      qualitative way. We found that nearly one third of the men can be described as
      "supportive". This finding strongly correlates with the subjective experience of
      the corresponding wives. In the subgroup of women already suffering from
      prepartal psychiatric disorders before delivery, the majority of the men were
      rated and experienced as "non-supportive". Using the standardised Operationalised
      Psychodynamic Diagnostic questionnaire (OPD),we describe the personality
      structure of,support-ing" men and some resulting therapeutic consequences in "non
      supporting" cases. In addition,we found a remarkable reduction in the length of
      hospital stay in the families with supporting men.

PMID- 15252890
TI  - [Superficial siderosis of the CNS. Case report and literature review].
AB  - Superficial siderosis of the central nervous system is caused by destructive
      deposition of haemosiderin in the leptomeninges and subpial layers of the brain
      and spinal cord. This deposition is the result of continuous or recurrent, often
      clinically silent, haemorrhage in the subarachnoid space, eventually without an
      evident bleeding source. Cerebellar ataxia, progressive bilateral sensorineural
      hearing loss, pyramidal tract signs, and dementia are the major clinical
      findings. The diagnosis is supported in vivo by the characteristic symptom
      constellation,xanthochromic cerebrospinal fluid,and typical MRI findings which
      show on the surface of the brainstem, cerebellum, cortex, and spinal cord. Early
      recognition of this rare entity may be of relevance for the further course and
      prognosis.

PMID- 15252891
TI  - Marketing myopia. 1960.

PMID- 15252892
TI  - The middle manager as innovator. 1982.

PMID- 15252894
TI  - [Organizational principles for orthodontic care for adolescents and adults].

PMID- 15252895
TI  - [Dental caries in elderly and aged population of Moscow and the Moscow suburbs].

PMID- 15252896
TI  - [Ethnic characteristics of dental crown sizes and their impact for orthodontic
      treatment with bridge dentures].

PMID- 15252897
TI  - [Use of subperiosteal implants for rehabilitation of patients with marked atrophy
      of bone tissue of the jaws].

PMID- 15252898
TI  - [Ceramic inserts made with the use of computer-aided shifting: advantages and
      drawbacks].

PMID- 15252899
TI  - [History of orthodontics: Prerequisites for development of the specialty].

PMID- 15252900
TI  - Nurses, information use, and clinical decision making--the real world potential
      for evidence-based decisions in nursing.

PMID- 15252901
TI  - Nurse led education plus direct access to imaging improved diagnosis and
      management of urinary tract infections in children.

PMID- 15252902
TI  - Review: antibiotics are moderately effective for acute otitis media in children.

PMID- 15252903
TI  - Review: delaying a prescription reduces antibiotic use in upper respiratory tract
      infections.

PMID- 15252904
TI  - A time limited, nurse led intervention reduced hospital readmissions in patients
      with asthma and a history of frequent admissions.

PMID- 15252905
TI  - A specialist nurse led liaison model of care reduced unscheduled care for acute
      asthma in a deprived multiethnic area.

PMID- 15252907
TI  - Review: patient education interventions improve glycaemic control in adults with
      diabetes mellitus.

PMID- 15252906
TI  - Websites offering information about depression or cognitive behaviour therapy
      reduced depressive symptoms.

PMID- 15252908
TI  - Adjustment of antihypertensive medication using home based, patient monitored
      blood pressure reduced both intensity of treatment and blood pressure control.

PMID- 15252909
TI  - Coaching by non-drug prescribing health professionals reduced total cholesterol
      concentrations in coronary heart disease.

PMID- 15252910
TI  - Cholesterol lowering with simvastatin reduced stroke in patients with, or at risk
      of, vascular disease.

PMID- 15252911
TI  - A nurse managed smoking cessation and relapse prevention programme did not reduce
      smoking rates at 12 months beyond rates achieved by usual care in women with
      cardiovascular disease.

PMID- 15252912
TI  - Review: single dose, oral paracetamol reduces moderate to severe postoperative
      pain.

PMID- 15252913
TI  - Review: silver alloy catheters are more effective than standard catheters for
      reducing bacteriuria in adults in hospital having short term catheterisation.

PMID- 15252914
TI  - Review: elastic compression stockings prevent post-thrombotic syndrome in
      patients with deep venous thrombosis.

PMID- 15252915
TI  - Review: long acting beta2 agonists and inhaled corticosteroids reduce
      exacerbations in chronic obstructive pulmonary disease.

PMID- 15252916
TI  - Review: screening instruments had sensitivities of 67-100% and specificities of
      53-98% for detecting major depression in older primary care patients.

PMID- 15252917
TI  - An evidence based algorithm for nutritional support accompanied by a multifaceted
      implementation strategy improved some outcomes in critically ill patients.

PMID- 15252918
TI  - Review: mothers with HIV infection worked hard to protect their children and
      preserve a positive maternal identity.

PMID- 15252919
TI  - The experiences of women who survived an attempt on their lives by an intimate
      partner represented a wide spectrum of previous violence and control issues in
      the relationship.

PMID- 15252920
TI  - After a stroke, women described changes that created a sense of bodily
      strangeness.

PMID- 15252921
TI  - Atrial fibrillation had a negative impact on quality of life, and treatment with
      an implantable cardioverter defibrillator with atrial therapies helped patients
      regain a sense of normalcy.

PMID- 15252922
TI  - 3 themes described how self care management was learned and experienced by
      patients with chronic illness.

PMID- 15252923
TI  - Care that ran smoothly, was responsive to clients' needs, and required no special
      effort for clients to maintain was important for continuity in home care.

PMID- 15252924
TI  - Patients' expressions of awareness of memory problems in early stage Alzheimer's
      disease reflected varying combinations of self maintaining and self adjusting
      styles of responding.

PMID- 15252925
TI  - Help for physicians contemplating use of e-mail with patients.

PMID- 15252926
TI  - COX-2 inhibition and colorectal cancer.
AB  - Mortality in patients with advanced colorectal cancer(CRC) remains high.
      Epidemiologic studies show that individuals taking nonselective, nonsteroidal
      anti-inflammatory drugs, including aspirin, have a significant reduction in CRC
      mortality, compared with those not taking these agents. The recent
      characterization of cyclooxygenase- I and -2 (COX- I and COX-2) isoforms has led
      to an expanded understanding of how nonsteroidal anti-inflammatory drugs may help
      prevent polyp formation. Cyclooxygenase enzymes are required for the conversion
      of arachidonic acid to prostaglandins.COX-2 mediates the inflammatory effects of
      COX activity, is induced by a wide spectrum of growth factors and proinflammatory
      cytokines, and is overexpressed in numerous premalignant and malignant lesions,
      including CRC. Treatment with the selective COX-2 inhibitor celecoxib has shown
      promising results in the prevention of CRC, Numerous studies show that this COX-2
      selective inhibitor is a potent suppressor of colon polyps both in animal models
      for familial adenomatous polyposis and in patients with this condition. This has
      led to the US Food and Drug Administration approval of celecoxib for the
      treatment of patients with familial adenomatous polyposis. The role of celecoxib
      in cancer treatment is still evolving. Recent studies have identified a potential
      benefit for adding celecoxib to standard CRC chemotherapy regimens to increase
      their efficacy and reduce their associated toxicity.

PMID- 15252927
TI  - COX-2 inhibition in upper aerodigestive tract tumors.
AB  - Evidence continues to accumulate that cyclooxygenase-2 (COX-2), an inducible COX
      isoform, represents a potential pharmacological target for the prevention and
      treatment of cancer, including tumors affecting the entire upper aerodigestive
      tract. Studies in experimental models of these malignancies show that selective
      COX-1 inhibitors reduce tumor formation and growth. Clinical studies have been
      initiated to determine the chemoprotective effects of selective COX-2 inhibitors
      in patients with oral leukoplakia and Barrett's esophagus, and other studies are
      assessing the feasibility of incorporating these agents into existing treatment
      modalities for patients with locally advanced or metastatic cancer.

PMID- 15252928
TI  - Gene patents: a myriad of issues.

PMID- 15252930
TI  - HIV/AIDS prevention carries on in rural India.

PMID- 15252929
TI  - Beneficial effects of statins on the kidney.

PMID- 15252931
TI  - WHA puts focus on HIV/AIDS treatment.

PMID- 15252932
TI  - Sudan Ebola outbreak of known strain.

PMID- 15252933
TI  - British scientists face law suit.

PMID- 15252934
TI  - STI testing for sperm, egg, and transplanted tissue donation.

PMID- 15252935
TI  - Polio vaccination to restart in Kenya.

PMID- 15252936
TI  - Sex hormones and ApoE4: beyond steroids.

PMID- 15252938
TI  - Need must......

PMID- 15252937
TI  - [Unacceptability of removing the conductance of specialization-bound partial
      radiological diagnostics from surgical practice].

PMID- 15252939
TI  - Ultrasonography and missed ectopic pregnancies.

PMID- 15252940
TI  - Evaluating the reconstitution of intramuscular ziprasidone (Geodon) into
      solution.

PMID- 15252941
TI  - Osteopathic emergency medicine.

PMID- 15252942
TI  - Fellowship training in critical care may not be helpful for emergency physicians.

PMID- 15252944
TI  - Out-of-hospital ultrasonographic diagnosis of a left ventricular wound after
      penetrating thoracic trauma.

PMID- 15252943
TI  - Insuring kids in hard times: since it began, SCHIP has been taking care of
      children's medical needs. The question now, however, is how will it be funded.

PMID- 15252945
TI  - Moving ahead with Olmstead: to comply with the American with Disabilities Act,
      states are working hard to find community placements for people with
      disabilities.

PMID- 15252946
TI  - Disclosure of medical errors.

PMID- 15252948
TI  - New WHO Director-General steps up global polio eradication effort as polio
      threatens other countries.

PMID- 15252947
TI  - "Do not attempt resuscitation" (DNAR) in the out-of-hospital setting.

PMID- 15252949
TI  - Failure to take prescribed medicine for chronic diseases is a massive, world-wide
      problem.

PMID- 15252950
TI  - Spina manipulative therapy for low back pain is effective only when compared to
      sham or ineffective treatments.

PMID- 15252952
TI  - Exercise improves self-esteem in children and young people.

PMID- 15252951
TI  - A negative result on the Ottawa knee rules excludes fracture in patients with
      acute knee injury.

PMID- 15252953
TI  - Home exercise reduces pain and improves function in construction workers with
      shoulder pain.

PMID- 15252954
TI  - Keeping lists and naming names: the rest of the story.

PMID- 15252955
TI  - All-terrain vehicle injuries: a growing epidemic.

PMID- 15252956
TI  - Abnormal D-dimer and negative computed tomography scan results do not exclude a
      pulmonary embolus.

PMID- 15252957
TI  - Psychiatry in pictures. Dementia (artist unknown, c. 1840).

PMID- 15252958
TI  - Turning points: implementing kinetic therapy in the ICU.
AB  - Kinetic therapy improves oxygenation, thus decreasing length of stay for patients
      with pulmonary disorders, such as nosocomial pneumonia, atelectasis, acute
      respiratory distress syndrome, and acute lung injury.

PMID- 15252959
TI  - [SARS infection].

PMID- 15252960
TI  - Encounter with crisis: Lessons I learned.

PMID- 15252961
TI  - [Contribution to EBM].

PMID- 15252963
TI  - Evidence that disgust evolved to protect from risk of disease.
AB  - Disgust is a powerful human emotion that has been little studied until recently.
      Current theories do not coherently explain the purpose of disgust, nor why a wide
      range of stimuli can provoke a similar emotional response. Over 40 000
      individuals completed a web-based survey using photo stimuli. Images of objects
      holding a potential disease threat were reported as significantly more disgusting
      than similar images with little or no disease relevance. This pattern of response
      was found across all regions of the world. Females reported higher disgust
      sensitivity than males; there was a constant decline in disgust sensitivity over
      the life course; and the bodily fluids of strangers were found more disgusting
      than those of close relatives. These data provide evidence that the human disgust
      emotion may be an evolved response to objects in the environment that represent
      threats of infectious disease.

PMID- 15252962
TI  - Classification of eubacteria based on their complete genome: where does
      Mycoplasmataceae belong?
AB  - The amino acid compositions of 11 Gram-positive and 12 Gram-negative eubacteria
      were determined from their complete genomes. They were classified into two
      groups, 'S-type' represented by Staphylococcus aureus and 'E-type' represented by
      Escherichia coli, based on their patterns of amino acid compositions determined
      from the complete genome. These two groups were characterized by their
      concentrations of Arg, Ala and Lys. Mycoplasmas, which lack a cell wall, belonged
      to the 'S-type', while Gram-positive mycobacteria belonged to the 'E-type'.
      Rickettsia prowazekii, Borrelia burgdorferi, Campylobacter jejuni and
      Helicobacter pylori, which are Gram-negative, belong to the 'S-type'. The
      classification into two groups based on their amino acid compositions determined
      from the complete genome was independent of Gram staining. In addition, the amino
      acid composition based on the plasmid resembled that based on the parent complete
      genome.

PMID- 15252964
TI  - Female choice of young sperm in a genetically monogamous bird.
AB  - When females copulate with multiple males the potential exists for female sperm
      choice. Females may increase the probability of being fertilized by preferred
      males by selectively retaining their sperm while ejecting the sperm of unfavoured
      males. An alternative criterion to male quality for female sperm choice may be
      sperm age because old sperm degrade and can lead to zygote death or unhealthy
      offspring. Here, we report that in a genetically monogamous bird, the black
      legged kittiwake Rissa tridactyla, females eject their mates' sperm according to
      when the copulations were performed. Following copulations that were performed
      approximately two weeks before egg laying, females ejected inseminations at high
      frequencies while retaining inseminations that occurred soon before laying.
      Females that suffered hatching failure had ejected sperm from early copulations
      less than half as frequently as females whose entire clutches hatched.
      Furthermore, chicks that hatched from eggs fertilized by old sperm were in poor
      condition relative to those fertilized by young sperm. These findings support the
      'young sperm' hypothesis, which predicts that females choose fresh sperm to avoid
      reproductive failure and are the first to show intra-male sperm choice by
      females.

PMID- 15252965
TI  - Acute undernutrition is not associated with excess of females at birth in humans:
      the Dutch hunger winter.
AB  - It has been suggested that maternal undernutrition results in adjustment of the
      sex ratio at birth, favouring females. We tested this hypothesis using births
      during the Dutch Hunger Winter of 1944-1945, an acute severe famine of seven
      months' duration. There was no evidence of an excess of female births among
      deliveries of human infants exposed to famine in any period in gestation. Indeed,
      among deliveries to women maximally exposed to famine prior to conception, there
      was an excess (odds ratio = 1.31, 95% CI 1.09-1.58; p = 0.004) of male offspring.
      Our data do not provide any support for acute and severe maternal undernutrition
      as a trigger for an increase in female conceptions or in male foetal deaths in
      human populations.

PMID- 15252966
TI  - Fit and fat from enlarged badges: a field experiment on male sand lizards.
AB  - To investigate the impact of nuptial coloration (the badge) on male fitness in
      the Swedish sand lizard (Lacerta agilis), we conducted a manipulation experiment
      in a natural population. Males in one group had their badges enlarged by being
      painted as cheaters and were compared to a control group with respect to mate
      acquisition, body condition and survival. Badge enlargement did not affect
      survival, but elevated mate acquisition by almost 400%, and body condition in
      small males. This increase in condition is likely to stem from greater access to
      female-associated sites with high food availability.

PMID- 15252967
TI  - Parent-offspring conflict and the coordination of siblings in gulls.
AB  - Offspring solicit food from their parents by begging behaviours. Studies on birds
      suggest that these displays are 'honest signals of need' and adults provide food
      according to the begging level. However, siblings may compete for parental
      resources and the begging intensity is expected to change with brood size. Here,
      we show that in the black-headed gull (Larus ridibundus) an increase of the
      numbers of siblings can result in a decrease of individual begging cost through
      nestlings' synchronized signalling. This is in accordance with some mathematical
      models. As parents respond to the total solicitation emerging from the nest, the
      probability to get food increases with the number of chicks begging together. The
      more siblings there are, the more they coordinate their begging while decreasing
      the number of individual begging bouts. Intra-brood synchronization of begging
      enables chicks to reduce their effort and hence exerting an important role in
      parental-offspring negotiation.

PMID- 15252968
TI  - A mosaic pattern characterizes the evolution of the avian brain.
AB  - Diversity in vertebrate brain size and composition is thought to arise from
      either developmental constraints that cause coordinated changes between brain
      regions or a mosaic model, whereby changes in individual brain regions are
      independent of changes in other brain regions. These two mechanisms were tested
      in birds using multiple regression analyses. Across 13 orders, significant
      correlations were present between some brain regions, but not all. Most of the
      correlated changes reflect the connectivity between different brain components,
      such that regions with the most interconnections are correlated with one another
      but not other brain regions. Whether mosaic changes are characteristic of brain
      regions or systems in birds, however, to our knowledge, remains to be
      investigated.

PMID- 15252969
TI  - Vertebrate host specificity of wild-caught blackflies revealed by mitochondrial
      DNA in blood.
AB  - Blood-feeding blackflies (Diptera: Simuliidae) transmit pathogens, harass
      vertebrate hosts and may cause lethal injuries in attacked victims, but with
      traditional methods it has proved difficult to identify their hosts. By matching
      mitochondrial DNA (mtDNA) sequences in blood collected from engorged blackflies
      with stored sequences in the GenBank database, relationships between 17 blackfly
      species and 25 species of vertebrate hosts were revealed. Our results demonstrate
      a predominance of large hosts and marked discrimination between blackflies using
      either avian or mammalian hosts. Such information is of vital interest in studies
      of disease transmission, coevolutionary relationships, population ecology and
      wildlife management.

PMID- 15252970
TI  - Mammalian microevolution in action: adaptive edaphic genomic divergence in blind
      subterranean mole-rats.
AB  - Genomic diversity of anonymous regions across the genome, most probably including
      coding and noncoding amplified fragment length polymorphisms (AFLPs), was
      examined in 20 individuals of the blind mole-rat, Spalax galili, one of four
      allospecies of the Spalax ehrenbergi superspecies of blind subterranean mole-rats
      in Israel. We compared 10 individuals from two nearby populations in Upper
      Galilee, separated by only a few dozen to hundreds of metres and living in two
      sharply contrasting ecologies: white chalk and rendzina soil with Sarcopterium
      spinosum and Majorana syriaca versus black volcanic basalt soil with Carlina
      hispanica-Psorelea bitominosa and Alhagi graecorum plant formations. The
      microsite tested ranged in an area of less than 10000 m2. Out of 729 AFLP loci,
      433 (59.4%) were polymorphic, with 211 soil unique alleles. Genetic polymorphism
      was significantly higher on the ecologically more xeric and stressful chalky
      rendzina soil than on the neighbouring mesic basalt soil. This is a remarkable
      pattern for a mammal that can disperse each generation between tens to hundreds
      of metres. These results cannot be explained by migration (which causes
      homogenization) or by chance (which will exclude sharp genomic soil divergence).
      Natural selection is the only evolutionary adaptive force that can cause genetic
      divergence across the genome matching the sharp microscale ecological contrast.

PMID- 15252971
TI  - Daily energy expenditure of male barn swallows correlates with tail-streamer
      length: handicap-mediated foraging strategies.
AB  - Daily energy expenditure (DEE) of male barn swallows (Hirundo rustica), measured
      using the doubly labelled water technique, correlated with streamer length.
      Contrary to predictions derived from previous findings, neither a positive linear
      nor a u-shaped relationship was found between DEE and streamer length. Instead,
      an n-shaped curve showed that the highest DEE corresponded to an intermediate
      streamer length of 119 mm. A model incorporating estimates of resting metabolism
      and flight energy expenditure from aerodynamics models suggested that variation
      in individual tail dynamics was the most likely explanation for the observed DEE.
      We suggest that streamer length is coupled to foraging strategy, because tail
      dynamics control flight performance, which in turn influences flight behaviour.

PMID- 15252972
TI  - Suction feeding in orchid bees (Apidae: Euglossini).
AB  - Energy flux during nectar feeding is maximized at an intermediate sugar
      concentration, the value of which depends on the morphology of the feeding
      apparatus and the modality of fluid feeding. Biomechanical models predict that a
      shift from capillary-based lapping to suction feeding will lead to a decrease in
      this optimal sugar concentration. Here, I demonstrate that the four major genera
      of orchid bees (Apidae: Euglossini) are suction feeders and provide experimental
      evidence that the feeding optimum for one species, Euglossa imperialis, falls
      below the optimum for bee taxa that lap.

PMID- 15252973
TI  - Non-territorial nightingales prospect territories during the dawn chorus.
AB  - Male songbirds usually sing when they have occupied a territory, but the
      territory prospecting of non-territorial males is more elusive and has been
      rarely studied. Here, we simulated newly arriving, non-territorial males by
      translocating unmated male nightingales (Luscinia megarhynchos) to our study
      site. We show that territory prospecting of translocated males was largely
      confined to the hour before sunrise. The radio-tagged males made extensive
      excursions visiting several singing males at dawn, but after dawn they remained
      stationary outside occupied territories. As in many other songbird species, dawn
      was also the time when resident males sang the most. These results suggest that
      nonterritorial male nightingales use the dawn chorus to assess singing residents
      or territory occupancy. For resident males, dawn singing may be important to
      announce territory occupancy to prospecting males and may thus play a role in
      territory maintenance.

PMID- 15252974
TI  - Discovery of a blue whale feeding and nursing ground in southern Chile.
AB  - After the extensive exploitation that reduced the Southern Hemisphere blue whale
      (Balaenoptera musculus) populations to less than 3% of its original numbers,
      studies on its recovery have been compounded by the inaccessibility of most
      populations and the extensive migrations between low and high latitudes, thus
      ensuring that knowledge about blue whale ecology and status remains limited. We
      report the recent discovery of, arguably, the most important blue whale feeding
      and nursing ground known to date in the Southern Hemisphere, which is located
      near the fjords off southern Chile. Through aerial and marine surveys (n = 7) 47
      groups, comprising 153 blue whales including at least 11 mother-calf pairs, were
      sighted during the austral summer and early autumn of 2003. The implications of
      this discovery on the biological understanding and conservation of this
      endangered species are discussed.

PMID- 15252975
TI  - Syphilis in renaissance Europe: rapid evolution of an introduced sexually
      transmitted disease?
AB  - When syphilis first appeared in Europe in 1495, it was an acute and extremely
      unpleasant disease. After only a few years it was less severe than it once was,
      and it changed over the next 50 years into a milder, chronic disease. The severe
      early symptoms may have been the result of the disease being introduced into a
      new host population without any resistance mechanisms, but the change in
      virulence is most likely to have happened because of selection favouring milder
      strains of the pathogen. The symptoms of the virulent early disease were both
      debilitating and obvious to potential sexual partners of the infected, and
      strains that caused less obvious or painful symptoms would have enjoyed a higher
      transmission rate.

PMID- 15252977
TI  - Tipsy punters: sauropod dinosaur pneumaticity, buoyancy and aquatic habits.
AB  - Sauropod dinosaurs were the largest terrestrial animals to have ever existed, and
      are difficult to interpret as living animals owing to their lack of living
      descendants. With computer models that employ the basic physics of buoyancy and
      equilibrium, it is possible to investigate how the bodies of these animals would
      have reacted when immersed in water. Multi-tonne sauropods are found to be
      extremely buoyant and unstable in water when aspects of their probable
      respiratory anatomy are considered, which obviates the old problem of them being
      unable to breathe when fully immersed. Interpretations of 'manus-only' trackways
      made by floating sauropods will depend on the details of buoyancy as not all
      sauropods float in the same manner.

PMID- 15252976
TI  - Do pretty women inspire men to discount the future?
AB  - Organisms 'discount the future' when they value imminent goods over future goods.
      Optimal discounting varies: selection should favour allocations of effort that
      effectively discount the future relatively steeply in response to cues promising
      relatively good returns on present efforts. However, research on human
      discounting has hitherto focused on stable individual differences rather than
      situational effects. In two experiments, discounting was assessed on the basis of
      choices between a smaller sum of money tomorrow and a larger sum at a later date,
      both before and after subjects rated the 'appeal' of 12 photographs. In
      experiment 1, men and women saw either attractive or unattractive opposite-sex
      faces; in experiment 2, participants saw more or less appealing cars. As
      predicted, discounting increased significantly in men who viewed attractive
      women, but not in men who viewed unattractive women or women who viewed men;
      viewing cars produced a different pattern of results.

PMID- 15252978
TI  - Autumn coloration as a signal of tree condition.
AB  - Hamilton and Brown suggested that bright autumn coloration in trees is an
      energetically expensive and therefore honest (handicap) signal of defensive
      commitment against insects. If this is so, one should expect that the intensity
      of the proposed signal should depend strongly on tree health. However, to the
      best of our knowledge, the link between vigour and autumn colour has never been
      tested. We explored the relationship between autumn coloration and tree condition
      (i.e. leaf fluctuating asymmetry) in mountain birch (Betula pubescens). Our
      results indicate that bright autumn birches are in better condition and therefore
      consequently should be better at combating herbivores.

PMID- 15252979
TI  - Sex-specific response of a mosquito to parasites and crowding.
AB  - Host-parasite interactions are significantly influenced by the sex of the host
      and the environment in which the host is found. Sex-specific responses to
      parasite infection, however, may change according to the host environment. I
      examine the combined effect of parasite infection and crowding on males and
      females of the mosquito Aedes albopictus. At a high larval density, infected
      males experienced a greater relative reduction in body size than did infected
      females, whereas the pattern was reversed at low density. This experiment
      demonstrates the importance of the environment on sex-specific responses to
      parasites and contributes to a growing body of work examining sources of
      variation in host-parasite interactions.

PMID- 15252980
TI  - DNA taxonomy of a neglected animal phylum: an unexpected diversity of
      tardigrades.
AB  - A molecular survey technique was used to investigate the diversity of terrestrial
      tardigrades from three sites within Scotland. Ribosomal small subunit sequence
      was used to classify specimens into molecular operational taxonomic units (MOTU).
      Most MOTU were identified to the generic level using digital voucher photography.
      Thirty-two MOTU were defined, a surprising abundance given that the documented
      British fauna is 68 species. Some tardigrade MOTU were shared between the two
      rural collection sites, but no MOTU were found in both urban and rural sites,
      which conflicts with models of ubiquity of meiofaunal taxa. The patterns of
      relatedness of MOTU were particularly intriguing, with some forming clades with
      low levels of divergence, suggestive of taxon flocks. Some morphological taxa
      contained well-separated MOTU, perhaps indicating the existence of cryptic taxa.
      DNA sequence-based MOTU proved to be a revealing method for meiofaunal diversity
      studies.

PMID- 15252981
TI  - Increased fecundity associated with infection by a cytophaga-like intracellular
      bacterium in the predatory mite, Metaseiulus occidentalis.
AB  - The endosymbiont Wolbachia has gained widespread notoriety over the past decade
      because of its high infection frequency among arthropods, and the unique
      heterogeneity of the host reproductive effects that it has been implicated as
      causing to enhance its own spread. Recently, another endosymbiotic bacterium from
      the Cytophaga-Flavobacterium-Bacteroides phylum has been shown to be widespread
      among arthropods and manipulate its hosts' reproduction to enhance its own
      spread. We show that infection by this Cytophaga-like organism (CLO) in the
      predatory mite Metaseiulus occidentalis (Acari: Phytoseiidae) is associated with
      a significant increase in the fecundity of infected females. This adds to the
      growing list of phenotypes that the CLO can induce in its hosts, which now
      include feminization, parthenogenesis induction, cytoplasmic incompatibility and
      fecundity enhancement, rivalling Wolbachia for overall diversity of host
      reproductive manipulations.

PMID- 15252982
TI  - Predator-prey coevolution: Australian native bees avoid their spider predators.
AB  - Australian crab spiders Thomisus spectabilis manipulate visual flower signals to
      lure introduced Apis mellifera. We gave Australian native bees, Austroplebia
      australis, the choice between two white daisies, Chrysanthemum frutescens, one of
      them occupied by a crab spider. The colour contrast between flowers and spiders
      affected the behaviour of native bees. Native bees approached spider-occupied
      flowers more frequently. However, native bees avoided flowers occupied by spiders
      and landed on vacant flowers more frequently. In contrast to honeybees that did
      not coevolve with T. spectabilis, Australian native bees show an anti-predatory
      response to avoid flowers occupied by this predator.

PMID- 15252983
TI  - A strong association between immune responsiveness and natal dispersal in a
      songbird.
AB  - Because parasite faunas typically show considerable spatio-temporal variation,
      and because parasites can have important fitness consequences, host defence
      mechanisms, including the immune system, can be expected to coevolve with natal
      dispersal, i.e. the movement of a newborn individual from its site of birth to
      its first site of reproduction. We demonstrate that immigrant individuals show a
      significantly higher humoral immune response towards a novel antigen than do
      local recruits in two independent populations of the great tit (Parus major).
      There was no effect of age, sex, tarsus length or body mass on immune
      responsiveness. Our results are consistent with the idea that phenotype-dependent
      dispersal and/or dispersal-by-phenotype-dependent selection establish a relation
      between immune responsiveness and natal dispersal.

PMID- 15252984
TI  - Ticks need not bite their red grouse hosts to infect them with louping ill virus.
AB  - For pathogens transmitted by biting vectors, one of the fundamental assumptions
      is often that vector bites are the sole or main route of host infection. Here, we
      demonstrate experimentally a transmission route whereby hosts (red grouse,
      Lagopus lagopus scoticus) became infected with a member of the tick-borne
      encephalitis virus complex, louping ill virus, after eating the infected tick
      vector. Furthermore, we estimated from field observations that this mode of
      infection could account for 73-98% of all virus infections in wild red grouse in
      their first season. This has potential implications for the understanding of
      other biting vector-borne pathogens where hosts may ingest vectors through
      foraging or grooming.

PMID- 15252985
TI  - Asexual populations of the invasive weed Oxalis pes-caprae are genetically
      variable.
AB  - Oxalis pes-caprae, a native of South Africa is a very successful, globally widely
      distributed, aggressive colonizer weed. It spreads vegetatively (through bulbils
      and underground shoots) in most of its colonized areas. In Israel, it is
      characterized by the total lack of seed set. Using 121 amplified fragment length
      polymorphism (AFLP) putative loci we have analysed the genetic structure of five
      representative populations in Israel. Despite the complete lack of sexual
      reproduction and the total dependency on vegetative dispersal, populations were
      found to be genetically variable. Surprisingly, considerable genetic diversity
      was found within and between all of the populations tested. We speculate that
      this diversity could be the result of an accumulation of mutations or genome
      rearrangement.

PMID- 15252986
TI  - Effects of male sterility on female remating in the mediterranean fruitfly,
      Ceratitis capitata.
AB  - Mating-induced reductions in female receptivity are common in insects. These
      responses are of interest because of their utility in insect pest control. In
      addition, the control of receptivity is likely to be the subject of sexual
      conflict over remating frequency. We investigated the specific effect of male
      sterility on female receptivity in an important pest species, the Mediterranean
      fruitfly (medfly), in which sterile males are often used for population
      suppression. Sterile males performed less courtship, obtained significantly fewer
      first and second matings than fertile males, and reduced female receptivity
      significantly less effectively than did fertile males. We modelled the likelihood
      of fertile matings and show that the low mating success of sterile males
      represents a significant problem for medfly sterile insect technique (SIT)
      programmes.

PMID- 15252987
TI  - Pollinator attractiveness increases with distance from flowering orchids.
AB  - Orchids are extraordinary among plants because many species are pollinated
      through sexual duplicity by producing flowers that mimic female insects to lure
      unsuspecting males. Previous work showed that sexual deception by the orchid
      Chiloglottis trapeziformis can have a negative impact on its wasp pollinator
      Neozeleboria cryptoides. We report that female wasps may be capable of mitigating
      the cost of the orchids' deception. Although male wasps quickly habituated to
      areas planted with unrewarding flower decoys, we found that the effectiveness of
      the chemical cue used by the wingless females to attract males increases with
      increasing distance from an orchid patch. The apparent specificity of the males'
      site-based avoidance strategy means that females emerging in areas occupied by
      flowering orchids could, potentially, leave the orchid colony by walking to
      increase their attractiveness.

PMID- 15252988
TI  - Stable isotope ratios indicate that body condition in migrating passerines is
      influenced by winter habitat.
AB  - Although predicted some time ago, there has been little success in demonstrating
      that the overall fitness of migratory birds depends on the combined influences of
      their experiences over all seasons. We used stable carbon isotope signatures
      (delta13C) in the claws of migrating black-throated blue warblers Dendroica
      caerulescens to infer their wintering habitats and investigated whether winter
      habitat selection can be linked to condition during migration. Resident bird
      species with low delta13C corresponded to selection of more mesic habitats, and
      migrating birds with low delta13C were in better condition than conspecifics with
      higher delta13C signatures. These findings concur with empirical observations on
      the wintering grounds, where dominants (mostly males) tend to exclude
      subordinates from mesic areas (considered to be high-quality habitats). We
      believe that variation in condition during migration may be one of the key
      factors determining differences in arrival times and condition at the breeding
      areas, which in turn have a major influence on reproductive success.

PMID- 15252989
TI  - A general rule for the dependence of developmental rate on temperature in
      ectothermic animals.
AB  - In animals that do not regulate their body temperature by the production of heat,
      the proportion of the total developmental time spent in a particular
      developmental stage does not change with temperature. In the quasi-linear region
      of the relationship between developmental rate and temperature, all of the
      developmental stages appear to have the same species-specific lower developmental
      threshold. This trait, which is called developmental isomorphy, constrains
      developmental adaptations of ectotherms to their environments and facilitates the
      precise timing of life-history events.

PMID- 15252990
TI  - Constraints on muscular performance: trade-offs between power output and fatigue
      resistance.
AB  - An important functional and evolutionary constraint on the physical performance
      of vertebrates is believed to be the trade-off between speed and endurance
      capacity. However, despite the pervasiveness of physiological arguments, most
      studies have found no evidence of the trade-off when tested at the whole-animal
      level. We investigated the existence of this trade-off at the whole-muscle level,
      the presumed site of this physiological conflict, by examining inter-individual
      variation in both maximum power output and fatigue resistance for mouse extensor
      digitorum longus (EDL) muscle using the work-loop technique. We found negative
      correlations between several measures of in vitro maximum power output and force
      production with fatigue resistance for individual mouse EDL muscles, indicating
      functional trade-offs between these performance parameters. We suggest that this
      trade-off detected at the whole-muscle level has imposed an important constraint
      on the evolution of vertebrate physical performance.

PMID- 15252991
TI  - Molecular evidence for a terrestrial origin of snakes.
AB  - Biologists have debated the origin of snakes since the nineteenth century. One
      hypothesis suggests that snakes are most closely related to terrestrial lizards,
      and reduced their limbs on land. An alternative hypothesis proposes that snakes
      are most closely related to Cretaceous marine lizards, such as mosasaurs, and
      reduced their limbs in water. A presumed close relationship between living
      monitor lizards, believed to be close relatives of the extinct mosasaurs, and
      snakes has bolstered the marine origin hypothesis. Here, we show that DNA
      sequence evidence does not support a close relationship between snakes and
      monitor lizards, and thus supports a terrestrial origin of snakes.

PMID- 15252992
TI  - Maternal basking behaviour determines offspring sex in a viviparous reptile.
AB  - Two primary dichotomies within vertebrate life histories involve reproductive
      mode (oviparity versus viviparity) and sex determination (genotypic sex
      determination versus environmental sex determination). Although reptiles show
      multiple evolutionary transitions in both parameters, the co-occurrence of
      viviparity and environmental-dependent sex determination have heretofore been
      regarded as incompatible. Our studies on the viviparous lizard Niveoscincus
      ocellatus show that the extent of basking by a female influences the sex of her
      offspring. Critically, our data reveal this effect both in the field (via
      correlations between date of birth and litter sex ratio) and in a laboratory
      experiment (females with reduced basking opportunities produced more male
      offspring). Changes in thermoregulatory behaviour thus allow pregnant female
      lizards to modify the sex of their offspring.

PMID- 15252993
TI  - The relationship between sexual dimorphism in human faces and fluctuating
      asymmetry.
AB  - Previous studies have found both support and lack of support for a positive
      relationship between masculinity and symmetry, two putative signs of mate
      quality, in male faces. We re-examined this relationship using an explicit
      measure of facial fluctuating asymmetry, as well as other measures of asymmetry,
      and measures of facial masculinity/femininity. We also used ratings of these
      traits for faces. Further, we examined the relationship between facial sexual
      dimorphism and body asymmetry. We found no significant correlations between
      facial masculinity and any of our measures of asymmetry or ratings of symmetry in
      males. Facial femininity was not consistently associated with facial symmetry in
      females, but was associated with body symmetry. Therefore, for females, but not
      males, facial femininity and body symmetry may reflect similar aspects of mate
      quality. We also examined the relationships between trait ratings and
      measurements. Our results provide validation of our ability to measure aspects of
      asymmetry that are perceived to be symmetrical, and aspects of sexual dimorphism
      that are perceived as feminine in females and masculine in males.

PMID- 15252994
TI  - Structurally assisted blackness in butterfly scales.
AB  - Surfaces of low reflectance are ubiquitous in animate systems. They form
      essential components of the visual appearance of most living species and can
      explicitly influence other biological functions such as thermoregulation. The
      blackness associated with all opaque surfaces of low reflectivity has until now
      been attributed to strongly absorbing pigmentation alone. Our present study
      challenges this assumption, demonstrating that in addition to the requirement of
      absorbing pigmentation, complex nano-structures contribute to the low reflectance
      of certain natural surfaces. We describe preliminary findings of an investigation
      into the nature of the black regions observed on the dorsal wings of several
      Lepidoptera. Specifically, we quantify the optical absorption associated with
      black wing regions on the butterfly Papilio ulysses and find that the
      nanostructure of the wing scales of these regions contributes significantly to
      their black appearance.

PMID- 15252995
TI  - Development of flight performance in the brown booby.
AB  - How do birds acquire flight skills after fledging? This issue is important, as it
      is closely related to variation in the duration of offspring care, the causes of
      which remain unknown. In this study, we raised hatchling brown boobies, Sula
      leucogaster, and attached an acceleration data logger to each bird at fledging to
      record its movements. This allowed us to quantify precisely the time spent
      flapping, gliding and resting. The duration of foraging trips and proportion of
      time spent gliding during flight increased with the number of days since
      fledging, whereas the proportion of time spent in flight decreased. This
      indicates that brown boobies gradually acquire efficient flight skills during the
      post-fledging period, which might be the proximate cause of the long postfledging
      care period in this species. To the authors' knowledge, this is the first study
      to record precisely the ontogeny of flight behaviour in birds.

PMID- 15252996
TI  - Kin recognition in rattlesnakes.
AB  - Snakes are often regarded as the least social of all vertebrate groups, but this
      assumption stems from the fact that they are secretive and difficult to observe
      in nature, rather than direct evidence. Recent studies have revealed a surprising
      degree of social complexity in snakes. Here, I examine the ability of captive
      raised timber rattlesnakes (Crotalus horridus) to recognize siblings by measuring
      the mean separation distance and frequency of contact between pairs of
      individuals housed together. The results show that female siblings associate more
      closely with each other than nonsibling pairs. Previous studies have shown that
      timber rattlesnakes occupying the same hibernacula have higher relatedness than
      snakes using neighbouring hibernacula, and frequently form social aggregations.
      Rattlesnakes exhibit other characteristics consistent with advanced sociality,
      including group defence, conspecific alarm signals and maternal defence of young.
      These findings reinforce the notion that, rather than being solitary and asocial,
      some snake species may form family groups.

PMID- 15252997
TI  - The food consumption of the world's seabirds.
AB  - Improving knowledge of the population sizes of all the world's seabirds allows
      this provisional estimate of their annual food consumption. Knowing the body mass
      and energy density of prey it is possible to employ standard metabolic equations
      to estimate daily and hence annual consumption of a seabird. Using this approach,
      and assuming that, at the least, there are three individuals alive for every
      recorded breeding pair, the annual food consumption of all the world's seabirds
      is 70 million tonnes (Mt: 95% CI 55.9-83.7 Mt). The total obviously increases if
      more liberal assumptions are made about the number of individuals alive per
      breeding pair. The principal consumers are mostly high-latitude, often pelagic
      species-penguins, petrels and auks. The total is similar to the global fisheries
      landings, currently ca. 80 Mt.

PMID- 15252998
TI  - Observation of a ZZW female in a natural population: implications for avian sex
      determination.
AB  - Avian sex determination is chromosomal; however, the underlying mechanisms are
      not yet understood. There is no conclusive evidence for either of two proposed
      mechanisms: a dominant genetic switch or a dosage mechanism. No dominant sex
      determining gene on the female-specific W chromosome has been found. Birds lack
      inactivation of one of the Z chromosomes in males, but seem to compensate for a
      double dose of Z-linked genes by other mechanisms. Recent studies showing female
      specific expression of two genes may support an active role of the W chromosome.
      To resolve the question of avian sex determination the investigation of birds
      with a 2A: ZZW or 2A: ZO genotype would be decisive. Here, we report the case of
      an apparent 2A: ZZW great reed warbler (Acrocephalus arundinaceus) female
      breeding in a natural population, which was detected using Z-linked
      microsatellites. Our data strongly suggest a role of W-linked genes in avian sex
      determination.

PMID- 15252999
TI  - Territory inheritance in clownfish.
AB  - Animal societies composed of breeders and non-breeders present a challenge to
      evolutionary theory because it is not immediately apparent how natural selection
      can preserve the genes that underlie non-breeding strategies. The clownfish
      Amphiprion percula forms groups composed of a breeding pair and 0-4 non-breeders.
      Non-breeders gain neither present direct, nor present indirect benefits from the
      association. To determine whether non-breeders obtain future direct benefits, I
      investigated the pattern of territory inheritance. I show that non-breeders stand
      to inherit the territory within which they reside. Moreover, they form a perfect
      queue for breeding positions; a queue from which nobody disperses and within
      which nobody contests. I suggest that queuing might be favoured by selection
      because it confers a higher probability of attaining breeding status than either
      dispersing or contesting. This study illustrates that, within animal societies,
      individuals may tolerate non-breeding positions solely because of their potential
      to realize benefits in the future.

PMID- 15253000
TI  - [Cancer in Brazil: present and future].

PMID- 15253001
TI  - [Do we communicate adequately with our patients?].

PMID- 15253002
TI  - [Which approach in patient with non-small cell lung neoplasms and brain
      metastasis].

PMID- 15253003
TI  - [Conventional appendectomy: which is the best incision?].

PMID- 15253005
TI  - [Endometrial neoplasms. What to consider?].

PMID- 15253004
TI  - [Utilization of laryngeal Mask. It is an usual practice in pediatric?].

PMID- 15253006
TI  - [The surgery to reduce the pulmonary volume is an effective treatment for
      patients with severe emphysema ].

PMID- 15253016
TI  - [Relationship between calcium and protein in diet of women in climacteric].

PMID- 15253017
TI  - [Aortic coarctation in young woman with HAS ].

PMID- 15253018
TI  - [Syndrome of anti-basal membrane antibody].

PMID- 15253020
TI  - [Medicine of Urgency into the Brazil. Where are we going to?].

PMID- 15253021
TI  - [Prognostic value of lymphatic vessel and neural invasion in colorectal
      carcinoma].
AB  - OBJECTIVES: The paradoxical evolution of approximately one third of patients with
      colorectal cancer cataloged in Dukes stages B and C demonstrates the necessity of
      make useful other prognostic criteria. The presence of neural and lymphatic
      invasion of tumor cells was correlated with the prognosis of patients submitted
      to radical operation. METHODS: We performed a retrospective study on 320 patients
      with colo-rectal carcinoma, with mean age 58 years and 199 (62.2%) females.
      Neural invasion was assessed as positive if cancer cells infiltration into the
      perineurium or neural fasciculus was detected at the leading point. Lymphatic
      invasion was defined by cancer cells infiltration into a space limited by
      endothelium without muscular or elastic fibers. Those variable were associated to
      the original classification of Dukes. RESULTS: Lymphatic and neural invasion was
      demonstrated in 14.1% and 15% of 320 operation specimens respectively. The most
      frequent site of lymphatic and neural invasion was the rectum. The overall
      survival was 25% in the presence of neural invasion and 64% without neural
      invasion (p<.01). At the presence of lymphatic invasion, the overall survivals
      were 26.7% and 63.3%, respectively (p <0.01). The overall survival was always
      worse in the presence of the invasion neural, independently of the compromising
      or not of the lymphonodes. In patients of free lymphonodes, the lymphatic
      invasion identified sub-groups of sick with worse prognosis. The presence of
      these variable it identified in patients with tumors Dukes B, sub-group of worse
      prognosis. CONCLUSION: Neural and lymphatic invasion are important ways of spread
      of colorectal cancer and the presence of both is associated with worse prognosis.

PMID- 15253022
TI  - [Incidental and symptomatic kidney cancer: pathological features and survival].
AB  - BACKGROUND: Patients with early diagnosis of renal cell carcinoma (CCR) have
      higher chance of cure following surgical treatment. This study was set to compare
      the pathological characteristics between the surgical specimens and the survival
      of the patients with incidental and symptomatic CCR. METHODS: One hundred and
      fifteen patients with sporadic CCR were studied retrospectively following
      nephrectomy and divided into two groups. Group 1; 59 patients with incidental
      diagnosis and Group 2; 56 symptomatic patients. The mean age of the patients was
      59 years, with 86 men and 29 women. Radical nephrectomy was performed in 96
      patients and the conservative surgery was performed in the remaining 19.
      Comparison parameters included pathological outcome, specifically nuclear grade,
      pathological stage, size of the tumor and presence of microvascular invasion
      intratumoral and patients survival. RESULTS: Comparison between the two groups
      confirmed that the incidental tumors have smaller nuclear grade (p=0.003),
      smaller size (p=0.001), smaller incidence of microvascular invasion (p<0.001) and
      lower stage (p<0.001). Disease specific survival and recurrence free survival of
      the incidental group were statistically higher than the symptomatic group
      (p<0.001). CONCLUSION: Incidentally discovered CCR have more favorable
      pathological characteristics, the patients have disease free survival when
      compared to symptomatic CCR.

PMID- 15253023
TI  - [Pulmonary gas exchange under room air respiration in hypercapneic patients].
AB  - INTRODUCTION: The alveolar-capillary oxygen difference, P(A-a)O2, is important in
      the study of gas exchange disorders, however does not give us reliable results
      when applied to hypercapneic patients. On the other hand the venous admixture
      calculation, seems to be able to diagnose alveolar-capillary gas exchange
      difficulty of any kind. OBJECTIVE: Checking the reliability of the alveolar
      capillary oxygen difference to diagnose the alveolar-capillary disorder in face
      of alveolar hypoventilation, by using the venous admixture calculation as
      standard. METHODS: 83 blood gas analysis from patients with hypercapnia were
      submitted to venous admixture and P(A-a)O2 determination with the measured PaCO2
      and a fixed PaCO2 of 40 mmHg. The results where compared by correlation test.
      RESULTS: The mean partial pressure of arterial oxygen and carbon dioxide were
      respectively, 50.8+/-10.4 and 51.7+/-6.4 mmHg; the mean value of P(A-a)O2,
      amended P(A-a)O2 and venous admixture were respectively 26.6+/-10.2 mmHg, 40.4+/
      10.8 mmHg and 37+/-15.2%. The correlation coefficient between the venous
      admixture versus P(A-a)O2 was 0.61 p<0.00001 and the venous admixture versus
      "amended" P(A-a)O2 was 0.89 p<0.00001. CONCLUSION: The use of the oxygen alveolar
      capillary gradient in chronically hypercapneic patient does not reach the
      diagnosis of alveolar-capillary gas exchange disorder which usually comes
      together with alveolar hypoventilation.

PMID- 15253024
TI  - [Prognostic value of plasmatic fibronectin and Child-Pugh classification in
      alcoholic cirrhotic patients. A comparative study].
AB  - BACKGROUND: To assess the prognostic value of plasmatic fibronectin (FN),
      compared to numeric Child-Pugh classification and its biochemical parameters in
      patients with alcoholic cirrhosis followed prospectively during a 18 months
      period. METHODS: Fifty patients with the diagnosis of cirrhosis by hepatic biopsy
      or clinical and biochemical criteria, were included in the study after the
      exclusion of hepatocarcinoma and GI bleeding, infection or continous alcohol
      ingestion in the last 30 days. The mean age was 51.3+/-12.6 years, being 72%
      males and 17 of them were classified as Child-Pugh A, 18 as B and 15 as C. Serum
      bilirubin concentration was measured in autoanalyzer, protein electrophoresis was
      performed on cellulose acetate and prothrombin time by the Quick test. Plasmatic
      FN was assessed by radial immunodiffusion with anti-human FN in 1% agarose gel
      slabs. RESULTS: One patient was excluded because no natural death and 12 died
      owing to hepatic disease. The numeric Child-Pugh [score > 10, Relative Risk
      (RR)=11.33] and total bilirubins (> 2.5 mg/dL, RR=9.47) were the best predictors
      of death. Mean plasmatic FN concentration was significantly higher among those
      who survived when compared with those who died (185+/-66 mg/L x 131+/-38 mg/L,
      p<0.01), with a RR=6.59, for FN < 165 mg/L. Higher levels of FN, on the other
      hand, were the best variable to predict survival, since 96% of these 29 patients
      were alive at the end of follow-up. CONCLUSION: Although having less accuracy in
      predicting the risk of death of these patients, plasmatic FN > 165 mg/L was
      better predictor of survival than Child-Pugh score or any one of its biochemical
      parameters.

PMID- 15253025
TI  - [Desire for information and participation in therapeutic decisions concerning
      severe diseases, in patients of a university hospital].
AB  - BACKGROUND: The purpose of our study was to evaluate the desire of the patients
      on being informed about diagnosis of severe diseases, the desire to have their
      families informed about this situation and to participate in therapeutic
      decisions. METHODS: 363 patients (outpatients and inpatients) of a General
      Internal Medicine division of a University Hospital were interviewed. The
      questionnaire contained specific questions on their desire to be informed of the
      diagnosis in case of cancer or AIDS and on their desire to have their families
      informed as well. Specific questions on whether they wanted to be informed of and
      participate of the therapeutic discussion process in case of abdominal tumors
      were also included. RESULTS: 96.1% of men and 92.6% of women showed the desire of
      being informed in case of cancer diagnosis and 87.7% of men and 84.2% of women
      wanted to have their families informed, 94.2% of men and 91% of women wanted to
      know the diagnosis of AIDS. While 86% of women and 76.6% of men wanted be
      informed in the case of a diagnosis of an abdominal tumor, only 58.5% of women
      and 39.6% of men wanted to give their opinion about in the case of different
      therapeutic alternatives. The desire to participate in therapeutic decisions was
      significantly lower (p<0.05) in men, people older than 60 years and inpatients.
      CONCLUSIONS: Our results showed that the great majority of the population that
      seeks for medical support in a Brazilian university hospital wishes to be
      informed on this health condition, even in case of serious illness. In addition,
      there are intense familiar bonds that make patients want to have their families
      also informed.

PMID- 15253026
TI  - [Can energy drinks affect the effects of alcoholic beverages? A study with
      users].
AB  - OBJECTIVES: The pattern of use of energy drinks, alone or combined with alcoholic
      beverages, was evaluated in a criteria sample. METHODS: 136 volunteers aged 24 +/
      6 years, who had reported at least one previous use of energy drinks, answered a
      questionnaire on their pattern of use of energy drinks and alcoholic beverages.
      RESULTS: Most of the sample (76%) reported using energy drinks in combination
      with alcoholic beverages, preferably whisky (90%), vodka (37%) and beer (13%).
      Most of the sample (79%) also reported using energy drinks alone. In the latter
      case, 61% of them reported not feeling any effect, 10% reported happiness, 9%
      euphoria, 9% insomnia, 7% uninhibited behavior and 24% increase in physical
      vigor. Out of those who reported combined use with alcohol, 14% told not to feel
      different, 38% increase happiness, 30% euphoria, 11% insomnia, 27% uninhibited
      behavior and 24% increase of physical vigor. High level of variability was
      observed in the number of lifetime uses of energy drinks (14 +/- 16). However,
      there was certain constancy in the number of cans ingested per occasion (1.5 +/-
      0.7). CONCLUSIONS: It was observed that the effects of energy drinks are
      variable, probably depending on the dose and individual sensitivity. Some reports
      suggest interaction with alcohol, expressed as an increase in the excitatory
      effects or reduction in the depressive effects. The possible pharmacological
      mechanisms underlying this interaction are discussed.

PMID- 15253027
TI  - [Calcium/protein relation of women on the climacteric].
AB  - OBJECTIVE: To evaluate the calcium/protein relation of the diet of climacteric
      women. METHODS: In a transversal study the diet was evaluated of 154 women 35-65
      years old and matriculated in the Health Clinic of the Climateric Woman of Health
      Center of Public Health College of the Sao Paulo University. The food intake of
      calcium and protein was investigated by "24 hours recall" method. The evaluation
      of calcium/protein relation was made according to Massey and Heaney (1998), that
      is 20/1 (mg/g). RESULTS: The mean of intake of calcium was 624.9 mg, the mean of
      intake of protein was 86.7 g and the calcium/protein relation was 7/1 (624.9
      mg/86.7 g). CONCLUSION: The studied population presents inadequated consumation
      of the calcium and protein nutrients. It could result in serious risk for health.

PMID- 15253028
TI  - [Distal radius fractures: consistency of the classifications].
AB  - OBJECTIVE: The purpose of this study was to determine the intra-observer and
      interobserver reproducibility of Frykman, AO and Universal classifications for
      the fractures of the distal radius. METHODS: In this study, 40 radiographs of
      fractures of the distal radius were selected and classifed by orthopedists of
      different centers and levels of experience, determining the intra-observer and
      interobserver reproducibility of the classifications using Kappa statistic
      method. RESULTS: The medium intra-observer concordance observed was moderate to
      Frykman and Universal classifications and light to the AO system. The medium
      interobserver reproducibility was light in the two readings to Frykman and
      Universal classifications and despicable in the second reading of the AO
      classification. CONCLUSION: All the classifications used presented questionable
      interobserver reproducibility compromising the use of the three evaluated
      systems.

PMID- 15253029
TI  - [Association of angiotensin converting enzyme polymorphism and echocardiographic
      measures in young siblings of hypertensive parents].
AB  - OBJECTIVES: To evaluate angiotensin converting enzyme gene (ACE) polymorphism
      with transthoracic bidimensional echocardiogram of normotensive young medical
      students, siblings of hypertensive parents comparing them with those with
      normotensive parents. METHOD: We had studied 80 normotensive youngs divided in
      two groups. Hypertensive parents' normotensive young medical students 40 x
      Normotensive parents' and normotensive medical students. Exclusion criteria were
      hypertension, obesity, smoke, use of oral contraceptives, as well as those who
      use chronically drugs or the presence of any disease. The group has been enrolled
      between 1994 to 1996. 50 students made transthoracic bidimensional
      echocardiogram. The statistical analysis was done by "T-student" test. The
      evaluation of polymorphism ACE gene was studied in 80 people in each step: 1) 5
      mL of blood in EDTA tube, 2) extraction of DNA, 3) evaluation of DNA
      concentration by electrophoresis analyses; 4) Polymerase chain reaction with
      primer of ACE gene, 5) Analysis of polymorphism ACE gene by electrophoresis 6)
      Statistical analysis by Chi-square test. RESULTS: The group of students with
      hypertensive parents presented thicker interventricular septum (7.82 mm +/- 0.69
      against 7.38 mm +/- 0.8, p<0.05). On the other hand, we didn't find differences
      between the groups concerning ACE gene genotype: students with hypertensive
      parents DD: 42.5%, DI: 37.5%, II: 20% against Students with normotensive parents:
      DD: 37.5%, DI: 32.5%, II: 30%, (p=0.58), in addition we also did not find
      differences concerning the alleles Group of hypertensive parents: D: 61.25%, I:
      38.75% versus normotensive parents: D: 53.75%, I: 46.25%, p=0.33. We divided
      these groups into two in relation to the mean thickness of interventricular
      septum and left ventricular mass and we did not find any difference: in students
      with hypertensive parents group septum > 7.82 mm: DD: 32%, DI: 24%, II: 20% x
      septum < 7.82 mm: DD: 8%, DI: 12%, II: 4%, p=0.7) in normotensive parents group
      septum septum > 7.38 mm: DD: 28%, DI: 12%, II: 12% x septum < 7.38 mm: DD: 16%,
      DI: 16%, II: 16%, p=0.59). The study of the left ventricular mass in hypertensive
      parents group mass > 131.52 g: DD: 20.69%, DI: 13.79%, II: 6.9% x mass < 131.52 g
      DD: 24.24%, DI: 17.24%, II: 17.24%, (p=0.72) in normotensive parents group mass >
      117.11 g: DD: 30.43%, DI: 8.7%, II: 8.7% x mass < 117.11 g: DD: 13.04%, DI:
      21.74%, II: 17.39%, (p=0.17). CONCLUSION: We found differences between the
      thickness of the interventricular septum of normotensive students sibling of
      hypertensive parents and normotensive parents. On the other hand we didn't find
      any difference between the two groups concerning the ACE gene polymorphism as
      well as any relation of ACE gene and thickness of interventricular septum and
      interventricular left ventricular mass.

PMID- 15253030
TI  - [Assessment of educational objectives in two different curricular structures-
      Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil].
AB  - OBJECTIVE: The objective of the study was to assess the impact of the curricular
      change on the achievement of the educational objectives of the institution,
      analyzing the performance of graduating students, from the Faculty of Medicine of
      Ribeirao Preto, University of Sao Paulo, Brazil. METHODS: Techniques of
      recognized validity and reliability (MCQ, OSCE, PMP) were used for the evaluation
      of skills and competence in the cognitive, psychomotor and clinical domains.
      Three of the 3 final years classes educated according to the previous curricular
      structure (n=222) and three classes educated according to the new curricular
      structure (n=261) were evaluated during the study period. RESULTS: The
      performance of graduating students in these different tests permitted us to
      estimate the extent of achievement of 17 of the 36 intermediate educational
      objectives of the institution in the two curricular structures. Comparison of the
      two curricula demonstrated the absence of significant differences in the extent
      of achievement of ten of the 17 objectives. For six of the seven remaining
      objectives a significant increase (p<0.05) in the extent of achievement was
      observed with the new curricular structure. CONCLUSIONS. The results indicate
      that the new curricular structure was associated with a better performance of the
      students in cognitive skills related to general practice and in basic clinical
      and psychomotor skills.

PMID- 15253031
TI  - [Anular pancreas--pancreatic resection or duodenal by-pass].
AB  - PURPOSE: To present the authors experience managing anular pancreas and to
      compare the results found by the authors with the ones found in the literature.
      METHODS: A retrospective review of four patients treated at the Departamento de
      Cirurgia da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul
      with anular pancreas. The disease was present in three different ages: one in the
      neonatal age, one in childhood and two in the adulthood. Gastroduodenal
      obstructive symptoms were the most common. Abdominal pain was present in adult
      patients. The diagnostic investigation began with radiological studies such as
      upper gastrointestinal barium series, upper endoscopy and abdominal computed
      tomographic scan, although all the diagnoses required surgery for confirmation.
      The duodenoduodenostomy was the treatment of choice in the pediatric patients,
      and division of the anulus was carried out in the adults. RESULTS: All patients
      had symptomatic relief and postoperative recovery. The hospital stay ranged from
      9 to 12 days (median 10.5 days). There were no postoperative complications. All
      patients remain asymptomatic up to now. CONCLUSION: The rare condition of anular
      pancreas does not allow a more detailed and comparative study. The results of the
      authors showed that both gastrointestinal by-pass and division of the pancreas
      are effective and safe treatments.

PMID- 15253033
TI  - [Latex and banana allergies in children with myelomeningocele in the city of Rio
      de Janeiro].
AB  - PURPOSE: Recently, latex type I hypersensibility reactions were frequently
      described, mainly in children with myelomeningocele (MMC), which maintain earlier
      intimate and frequent contact with latex products. Allergic food cross-reactions
      are well known for many years. Nowadays, latex allergy is frequently associated
      with food allergies to avocado, banana, kiwi, grapefruit, papaya, chestnut and
      peach. BACKGROUND: The objective of this study consisted in identifying the
      number of patients with myelomeningocele (MMC) and banana-latex clinico
      laboratorial sensitization. METHODS: Questionnaires were applied to 33 children
      with MMC and blood was collected from 30 to perform latex IgE (RAST Pharmacia),
      and from 29 to banana IgE. Specific IgE equal or above class I was considered
      positive. RESULTS: Four children related histories of latex contact urticaria,
      and one child related a history of urticaria and diarrhea with banana. 14/30
      (46.6%) were latex IgE positive, and 4/29 (13.7%) to banana. There was no
      statistically significant association between variables. CONCLUSIONS: We
      identified high prevalence of latex and banana allergies in patients with MMC and
      we need more studies to analyze the prevalence of food-latex allergic cross
      reactions in children with MMC.

PMID- 15253032
TI  - [Quantification of the stone clinic effect in patients with nephrolithiasis].
AB  - BACKGROUND: The "stone clinic effect" refers to the effect of encouraging a high
      intake of fluid and diet counseling in the clinical evolution of kidney stone
      disease. OBJECTIVE: Our objective was to determine the extent of this variable in
      patients with nephrolithiasis. METHODS: Twenty-five patients (11 female and 14
      male, 47.64+/-10.55 years old) with recurrent nephrolithiasis were prospectively
      followed for one year, with 3-month interval medical evaluation. Patients were
      advised to increase the fluid intake, and to limit the intake of salt and
      protein. No patient was submitted to pharmacological therapy. Two 24-hour urine
      samples were collected at baseline (S1) and in the end of follow-up (S2) for the
      measurement of creatinine, calcium, sodium, uric acid, citrate, oxalate and
      magnesium. Metabolic and radiological activity was also assessed. Urinary calcium
      oxalate supersaturation (SS) was calculated by Tiselius index. RESULTS: Eleven
      (44%) patients had hypocitraturia, 9 (36%) hypercalciuria and 5 (20%)
      hyperuricosuria. Urinary volume increased (1903+/-811 vs. 2381+/-919 ml/day,
      p<0.05) and SS decreased significantly (1.13+/-0.8 vs. 0.6+/-0.2, p<0.01). During
      follow-up, the number of stones decreased when compared to baseline (S1 = 2.04+/
      1.51 vs. S2 = 0.72+/- 0.23 stones, p<0.001). There was no evidence of new stone
      formation or growth in 20 of 25 patients (80%). CONCLUSIONS: The "stone clinic
      effect" significantly decreased urinary SS for calcium oxalate and the formation
      of new kidney stones in 80% of patients during first year of follow-up.

PMID- 15253034
TI  - [Incidence and endoscopic characteristics of airway injuries associated
      endotracheal intubation in children].
AB  - OBJECTIVE: Describe the incidence and endoscopic characteristics of airway
      injuries in children submitted to intubation. METHODS: During a two-year period
      (October/1999-October/2001) we conducted a prospective study in which all
      patients that required intubation, excluding those who deceased before extubation
      and newborns (NB) weighing less than 1.250 g, were submitted to airway endoscopy
      at extubation. The endoscopic findings were classified as minor, moderate or
      severe. Descriptions were made through proportions and medians, comparisons were
      done through chi-square for proportions. RESULTS: We studied 61 NB and 154
      children. In 89.8%, 55 NB and 138 children (P=0.89), it was detected at least one
      lesion in a total of 507. Patients with minor lesions were 54.8% (IC95%: 48.1
      61.5), those with moderate were 24.2% (IC95%: 18.5-30.0) and severe injury
      occurred in 10.7% (IC95%: 6.6-14.8). Lesions at the glottis (48.1% of lesions)
      and subglottis (35.1%) presented the highest incidence. Erosions had the highest
      incidence in both age groups (P=0.88). Vocal folds edema was the main moderate
      lesion in both groups (P=0.96), followed by ulcerations (P=0.92). Fibrous nodules
      at vocal folds and adhesions were the main severe injuries in both groups
      (P=0.12). Subglottic stenosis was detected in 2.8% of the patients without
      difference between groups (P=0.35). CONCLUSIONS: We observed a high incidence of
      airway injury, without statistical significant difference between age groups in
      regard to the incidence and characteristics of the injuries. Minor injury was
      detected in the majority of the population. Lesions were mainly noticed at the
      glottis and were characterized by erosions, edema and ulcerations.

PMID- 15253035
TI  - [Snakebites in the State of Goias, Brazil].
AB  - Ophidic accidents are a serious health problem for tropical countries, because
      are responsible for the high incidence of morbidity and mortality. PURPOSE: This
      article describes aspects of snakebite epidemiology in the State of Goias,
      Brazil. METHODS: Notifications about the accidents caused by poisonous snakes
      have been analysed for Government of the State of Goias (Brazil), Health
      Department, from 1998 to 2000. RESULTS: In this period, 3261 accidents caused by
      poisonous snakes have been notified, which represented the average annual
      incidence rate of 20 to 23/100,000 persons. The vast majority of cases occurred
      from October to April. The classification of the snake genus had been possible in
      2350 cases and the distribution was: Bothrops (78.6%), Crotalus (20.8%) and
      Micrurus (6%). The age distribution shows that the accidents had been suffered by
      20 to 39 year old people with great predominance in males (78%). The anatomical
      areas more frequently bitten were feet (43.6%), legs (23.2%) and hands (20.1%).
      At the health center 80% of the patients had been treated within sixth hour after
      the accident. The distribution according to the severity of poisoning was: light
      (31.6%), moderate (47.5%) and severe (9.6%). The most common complications were
      necrosis bite site (31.8%) in bothropic envenoming and acute renal failure (1.2%)
      in crotalic envenoming. The case fatality rate was 0.46%, been the most rate
      observed in crotalic envenoming (1%). CONCLUSIONS: Accidents owing to poisonous
      snakes are frequent in the State of Goias, the young male population is more
      often attacked and they are an important cause of death.

PMID- 15253036
TI  - [Injury among the elderly: the challenge to integrate preventive activities in
      public and individual levels].
AB  - BACKGROUND: In Brazil and all over the world the elderly are increasing as a
      result of the raise in life expectancy. This group still faces a significant risk
      for some diseases as well as injuries. The proposal of this study was to describe
      fatal and nonfatal injuries among people aged 60 years and older in Brazil.
      SETTING: Brazil, the last year available was 2000. METHODS: The data from 13,383
      injury deaths and 87,177 outcomes among people aged 60 years and older were
      analyzed. The data sets were obtained from Federal Health Department of Brazil
      from Mortality System Information (from death certificates) and Hospitalization
      Information System (from discharges registered in public hospitals). RESULTS: The
      mortality rate is 92.1/100,000 (135.3/100,000 for male and 56.8/100,000 for
      female) that are higher than overall population rates, especially for women. The
      lead cause is transport accidents (27.5% of total injury deaths) which mortality
      rate is 25.3/100,000 and 48.2% are pedestrian. Homicides rate is 9.5/100,000, it
      is almost three times lower than for total population in Brazil. Falls rate is
      14.0/100,000, it is the third place in injury deaths for men and women and
      suicide rate is 6.9/100,000, lower than developed countries. Opposite to
      mortality, falls are the major cause of nonfatal injuries hospitalization for
      both men and women, accounting for 48,940 discharges (56.1%). Fractures are 52.8%
      of all injuries, especially in falls and transport accidents. CONCLUSIONS: It is
      crucial to develop injury preventive activities in both public and individual
      level. Falls should receive emphasis in injury prevention efforts.

PMID- 15253037
TI  - [Evidence-based clinical practice. Part II--Searching evidence databases].
AB  - The inadequacy of most of traditional sources for medical information, like
      textbook and review article, do not sustained the clinical decision based on the
      best evidence current available, exposing the patient to a unnecessary risk.
      Although not integrated around clinical problem areas in the convenient way of
      textbooks, current best evidence from specific studies of clinical problems can
      be found in an increasing number of Internet and electronic databases. The
      sources that have already undergone rigorous critical appraisal are classified as
      secondary information sources, others that provide access to original article or
      abstract, as primary information source, where the quality assessment of the
      article rely on the clinician oneself . The most useful primary information
      source are SciELO, the online collection of Brazilian scientific journals, and
      Medline, the most comprehensive database of the USA National Library of Medicine,
      where the search may start with use of keywords, that were obtained at the
      structured answer construction (P.I.C.O.), with the addition of boolean operators
      "AND", "OR", "NOT". Between the secondary information sources, some of them
      provide critically appraised articles, like ACP Journal Club, Evidence Based
      Medicine and InfoPOEMs, others provide evidences organized as online texts, such
      as "Clinical Evidence" and "UpToDate", and finally, Cochrane Library are composed
      by systematic reviews of randomized controlled trials. To get studies that could
      answer the clinical question is part of a mindful practice, that is, becoming
      quicker and quicker and dynamic with the use of PDAs, Palmtops and Notebooks.

PMID- 15253038
TI  - Formation of polychlorinated naphthalenes, dibenzo-p-dioxins, dibenzofurans,
      biphenyls, and organochlorine pesticides in thermal processes and their
      occurrence in ambient air.
AB  - Mono- through octachlorinated naphthalenes (PCNs) were measured in start-up,
      steady operation, and shutdown of machinery operation flue gas and fly ash
      generated during different stages of MSWI and other incineration thermal
      processes. Besides, electroprecipitator fly ash (EP-ash) was dechlorinated using
      the Hagenmeier process and analyzed for congener profiles. In addition to PCNs,
      polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls
      (PCBs), and major organochlorine pesticides were determined in ambient air
      samples from three different sites of western Japan in the summer and winter of
      1992. The PCNs from flue gas contained 15,000, 4300, and 13,000 ng/m3 during
      start-up, steady operation, and shutdown conditions, respectively. Whereas fly
      ash contained 470, 370, and 1400 ng/g PCNs under start-up, steady operation, and
      shutdown condition, respectively. The dechlorination process reduced PCN
      concentrations considerably. Concentrations of PCNs and PCDD/PCDFs in air samples
      collected in winter were slightly higher than in summer. PCBs, organochlorine
      pesticides such as chlordanes, DDTs, and HCHs were higher in summer air samples.
      WHO toxic equivalency (WHO-TEQ) concentrations in air samples were 0.3-0.9 pg/m3
      for PCDD/DFs and 0.029-0.31 pg/m3 for dioxin-like PCBs.

PMID- 15253039
TI  - Residues of hexachlorocyclohexane isomers and their distribution characteristics
      in soils in the Tianjin area, China.
AB  - Hexachlorocyclohexane (HCH) has a history of use in China. This paper presents
      the results of an investigation of HCH residue isomers and their distribution
      characteristics in soils near Tianjin, China. One hundred eighty-eight soil
      samples were collected from the Tianjin area. Four HCH isomers-alpha-HCH, beta
      HCH, gamma-HCH, and delta-HCH-were detected using gas chromatography for all
      samples. Concentrations of the sum HCH ranged from 1.3 to 1095 ng g(-1), among
      which beta-HCH accounted for 52.5%. In addition, residues of HCH within Tianjin's
      urban areas were found to be higher. No significant differences were found
      between the residues of HCH in soils from waste irrigation areas and those in
      other areas. Total organic carbon content was determined to impact the residue
      levels of HCH in soils, while pH value and clay content were not related to
      concentrations of HCH. In general, all HCH isomers in soil samples had abnormally
      high residue levels, possibly the result of continuous use of HCH in this area.

PMID- 15253041
TI  - Estimation of estrogenic and antiestrogenic activities of selected pesticides by
      MCF-7 cell proliferation assay.
AB  - Estrogenic activities of 20 selected pesticides-which are used for agricultural
      production as insecticides, fungicides and herbicides-were examined by estrogen
      receptor (ER)-dependent MCF-7 cell proliferation assay. Among them, chlordecone,
      dicofol, methoxychlor, gamma-HCH, fenarimol, EPN, triadimefon, and triadimenol
      had estrogenic activities, all of which were suppressed by the addition of pure
      antiestrogen ICI 182,780. The first 5 compounds exhibited binding capacities to
      ERalpha. The antiestrogenic activity of a compound was examined by estimating its
      suppressive effect on cell proliferation induced by 30 pM 17beta-estradiol.
      Strongly suspected antiestrogens were captan and myclobutanil, both of which were
      found to have the capacity to bind to ERalpha and which might exert their
      activities by competing at the level of ERalpha. Antiestrogenic activities of
      nitrofen, fenitrothion, fenarimol and triadimefon were also suggested. Affinities
      of the compounds for ERalpha and/or androgen receptor (AR) were lower than those
      of synthetic estrogen (diethylstilbestrol) and testosterone (mibolerone),
      respectively. Fenitrothion had the highest affinity to AR. Chlordecone, dicofol,
      methoxychlor, nitrofen, fenarimol, myclobutanil and pyridate had capacities to
      bind both ERalpha and AR. Chlordecone and pyridate were much more effective as
      competitors of estrogen binding to ERalpha than androgen binding to AR and,
      conversely, nitrofen was a more effective competitor of androgen binding to AR.

PMID- 15253040
TI  - Low-level atrazine exposure decreases cell proliferation in human fibroblasts.
AB  - There is continuing concern that release of certain chemicals into the
      environment leads to human exposure to toxins, particularly through contaminated
      ground and surface waters. The triazine herbicide atrazine (2-chloro-4-ethylamine
      6-isopropylamino-S-triazine) is routinely found as a contaminant in many surface
      and groundwaters. Little is known of the long-term effects of atrazine exposure
      on human cells. The objective of this research was to examine whether low-level
      exposure of atrazine to normal human fibroblast cells in culture had measurable
      deleterious effects. We show that low-level, short-term exposure of atrazine to
      normal fibroblasts results in decreased cell proliferation. In two separate
      assays to measure cell proliferation, either a 1.5-fold decrease in the cell
      number occurred (saturation density analysis) or a 2-fold decrease in cell
      proliferation was found (MTT analysis). Experiments to measure apoptosis in cells
      exposed to low levels of atrazine did not show DNA fragmentation or increased
      caspase activity. Thus, this analysis shows that short-term exposure to
      environmentally relevant, low levels of atrazine can be assessed by a decrease in
      cellular proliferation of normal human cells.

PMID- 15253042
TI  - Antiestrogenic effects of motorcycle exhaust particulate in MCF-7 human breast
      cancer cells and immature female rats.
AB  - The emissions from 2- and 4-stroke motorcycles pollute the air of urban areas
      where motorcycle is a popular means of transportation. This study aimed to
      determine the endocrine-disrupting activity of motorcycle exhaust particulate
      (MEP) using MCF-7 human breast cancer cells and immature female Wistar rats
      treated with organic extracts of MEP. Treatments with 1, 10, and 50 microg/ml MEP
      extract for 2 and 4 days produced dose-dependent inhibition of thymidine
      incorporation and cell growth, respectively, in untreated and 1 nM 17beta
      estradiol (E2)-treated cells. Treatments of MCF-7 cells with MEP extract replaced
      [3H]E2 from the estrogen receptor in a time- and concentration-dependent manner.
      These antiestrogenic and receptor binding properties of MEP extract were blocked
      by cotreatment of the cells with 2 microM alpha-naphthoflavone, a cytochrome P450
      inhibitor and aryl hydrocarbon receptor antagonist. E2 metabolism and HPLC
      analysis showed that treatment of MCF-7 cells with 50 microg/ml MEP extract for
      24 h increased E2 2- and 4-hydroxylation in microsomes. The MEP-mediated increase
      in E2 2-hydroxylation was inhibited by the addition of 1 microM alpha
      naphthoflavone to MCF-7 microsomes. Cotreatment of immature female rats with 10
      microg/kg E2 and 10 mg/kg MEP extract intraperitoneally for 3 days decreased the
      E2-induced uterine weights. MEP extract alone showed no effect on rat uterine
      weight. The endocrine-disrupting activity of MEP extract was further confirmed in
      parallel experiments using MCF-7 cells and immature female rats treated with
      benzo(a)pyrene, an MEP constituent compound. The present findings demonstrate
      that MEP extract is antiestrogenic in vitro and in vivo and cytochrome P450
      induction is an underlying mechanism.

PMID- 15253043
TI  - Acute effects of Microcystis aeruginosa from the Patos Lagoon estuary, southern
      Brazil, on the microcrustacean kalliapseudes schubartii (Crustacea: Tanaidacea).
AB  - Toxic blooms of the cyanobacterium Microcystis aeruginosa, a microcystin
      producer, have been observed in the past two decades in the Patos Lagoon estuary
      (southern Brazil). This cyanobacterium reaches the estuary from northern waters
      and accumulates as toxic blooms in the shallow margins of the environment.
      Microcystins are phosphatase (PP1 and PP2A) inhibitors and cause animal death via
      alteration of the liver cell cytoskeletons and intrahepatic hemorrhage. The
      massive accumulation of toxic material affects the survival of several benthonic
      estuarine local organisms. The tanaidacea Kalliapseudes schubartii is a benthonic
      estuarine species which occurs at high densities throughout the year in
      mixohaline areas of the Patos Lagoon. This microcrustacean is of high ecological
      relevance and plays an important role in the estuarine food web, as it is
      consumed on a large scale by estuarine fish. This work verifies the acute
      toxicity of aqueous extracts of M. aeruginosa RST9501 and of sediments spiked
      with lyophilized material of the same strain on K. schubartii; it also evaluates
      the sublethal effects on tanaidacean oxygen consumption rates and glycogen levels
      under acute exposure to M. aeruginosa aqueous extracts. The strain M. aeruginosa
      RST9501 was cultured in BGN/2 medium. The aqueous extracts were prepared using
      the lyophilized material from the strain cultures. Acute tests were performed
      over 96 h at a salinity of 15, at six toxic concentrations, and resulted in an
      average 96-h LC50 of 1.44 mg ml(-1). The spiked sediment tests were performed
      with a 10-day duration, using the lyophilized material in three proportions of
      powder/sediment and showed an average LC50 of 1.79 mg ml(-1). Oxygen consumption
      was determined after 24 and 48 h of incubation in adult organisms exposed to
      sublethal aqueous extract concentrations and showed a significant increase at the
      highest concentrations. This suggests alterations in the organism's metabolism by
      exposure to the cyanobacterium extract. The glycogen levels were determined with
      a commercial kit (Glicox 500; DOLES Ltd.); after 24 and 48 h the dosages were
      administered in the same organisms utilized in the oxygen consumption test and
      did not demonstrate significant differences. The results demonstrate the possible
      risks of intoxication to which the natural populations of K. schubartii were
      exposed in the environment and emphasize the importance of studies involving
      sublethal concentrations of M. aeruginosa to other organisms of the trophic web
      in this aquatic system.

PMID- 15253044
TI  - Effect of herbal molluscicides and their combinations on the reproduction of the
      snail Lymnaea acuminata.
AB  - Effects of sublethal treatment (20 and 60% of LC50/24 h) of the plant-derived
      molluscicides Annona squamosa Linn. and Lawsonia inermis Linn. and their
      combinations with other herbal molluscicides, such as Cedrus deodara Roxb,
      Azadirachta indica A. Juss, bulb powder of Allium sativum Linn. and Polianthes
      tuberosa Linn., and oleoresin of Zingiber officinale Rosc., and acetogenins
      extracted from the seeds of A. squamosa Linn., on the reproduction of the snail
      Lymnaea acuminata have been studied. It was observed that the plant-derived
      molluscicides singly and in binary combinations with other herbal molluscicides
      and the extracted acetogenins caused a significant reduction in the fecundity,
      hatchability, and survival of young snails. Withdrawal of the snails to fresh
      water after the above treatment caused a significant recovery in the fecundity of
      the snail Lymnaea acuminata. Twenty-four-hour sublethal treatment with the
      acetogenins caused a maximum reduction in the protein, amino acid, DNA, and RNA
      in the ovotestis of treated Lymnaea acuminata.

PMID- 15253045
TI  - Aquatic snails from mining sites have evolved to detect and avoid heavy metals.
AB  - Toxicants in polluted environments are often patchily distributed. Hence, rather
      than being passive absorbers of pollution, some organisms have evolved the
      ability to detect and avoid toxicants. We studied the avoidance behavior of
      Physella columbiana, an aquatic pulmonate snail, in a pond that has been polluted
      with heavy metals for more than 120 years. Populations of this snail are rare at
      reference sites and are only robust at heavy-metal-polluted sites. We
      hypothesized that the snails are able to persist because they have evolved the
      ability to minimize their exposure to metals by actively avoiding metals in their
      environment. Using a Y-maze flow tank, we tested the avoidance behavior of snails
      to heavy-metal-polluted sediments and single-metal solutions of cadmium, zinc, or
      lead. We also tested the avoidance behaviors of the snails' laboratory-reared
      offspring raised in nonpolluted conditions. In addition, we tested the avoidance
      behavior of a small population of snails from a reference pond. Although all the
      snails we tested were able to detect low concentrations of heavy metals, we found
      that snails from the polluted site were the most sensitive, that their offspring
      were somewhat less sensitive, and that snails from the reference site were the
      least sensitive. This suggests that the ability of polluted-site snails to avoid
      heavy metals is both genetic and environmental. The concentrations of metals
      avoided by the snails from the polluted site were below the levels found at hot
      spots within their natal pond. The snails may be able to persist at this site
      because they decrease their exposure by moving to less-polluted sections of the
      pond. One application of our findings is the use of aquatic snails and our Y-maze
      design as an inexpensive pollution detector. Environmental pollutants such as
      lead, zinc, and arsenic are a problem throughout the world. People in
      underdeveloped countries often lack sophisticated pollution detection devices. We
      have developed a behavioral assay of aquatic pollution that is easy to use, is
      extremely sensitive (detection below 10 ppb), and can be constructed for fewer
      than 100 US dollars. Pulmonate snails are widely distributed in tropical,
      subtropical, and temperate parts of the globe, and they are often common in
      polluted waters. For countries such as India and Bangladesh, which must test
      thousands of shallow wells for possible contamination with heavy metals, our
      assay would be a good initial test. Once snails detected metals, then those
      samples could be confirmed by spectrometers. We encourage scientists in
      underdeveloped nations to consider our assay as an option.

PMID- 15253046
TI  - Heavy metals in sediments and lobster (Panulirus gracilis) from the discharge
      area of the submarine sewage outfall in Mazatlan Bay (SE Gulf of California).
AB  - Concentrations of selected heavy metals in lobster (Panulirus gracilis) tissues
      and sediments (bulk and bioavailable fractions) from an area influenced by sewage
      discharge in Mazatlan Bay were determined. Cd, Cu, Fe, Pb, and Zn in the
      sediments showed enrichment factors higher than one related to the discharge and
      were higher than the lower values of the sediment quality guidelines proposed by
      NOAA and CCME. In addition to the high levels, relatively high bioavailability in
      the sediments was estimated for Cd, Cu, Mn, Pb, and Zn, suggesting a possible
      adverse effect on the associated benthic organisms. A high concentration of Cr,
      Fe, Mn, and Ni was found in the exoskeleton of P. gracilis. The hemolymph,
      hepatopancreas, gills, and gonads concentrate Cu, Cd, and Zn to levels higher
      than the available concentration in the sediments (BCF > 1). However, most of the
      metals studied in the edible muscle tissue in P. gracilis ranged within the
      recommended limits for human consumption, except Pb, which was found to be above
      the acceptable level for shellfish and represents a health risk.

PMID- 15253047
TI  - Tumor prevalence and biomarkers of exposure in brown bullhead (Ameiurus
      nebulosus) from Back River, Furnace Creek, and Tuckahoe River, Maryland.
AB  - Brown bullheads (Ameiurus nebulosus) were collected from 2 locations near
      Baltimore, Maryland, Back River and Furnace Creek, and 1 (reference) location,
      Tuckahoe River, to compare the prevalence of tumors (liver and skin) and visible
      skin lesions (fin erosion and abnormal barbels). Cytochrome P450 activity
      measured as ethoxyresorufin-O-deethylase, biliary PAH-like fluorescent
      metabolites, and fillet contaminant concentrations were determined as indicators
      of exposure in a randomly selected subset of the fish. There were no significant
      differences in liver tumor prevalence: Back River = 8% (4/50), Furnace Creek = 0%
      (0/50), and Tuckahoe River = 2.6% (1/39; p = 0.20, extension of Fisher's exact
      test). Skin tumor prevalence was as follows: Furnace Creek = 12% (6/50), Back
      River = 8% (4/50), and Tuckahoe River = 0% (0/39; p = 0.063). In the Back River
      fish, there was a 40% (20/50) prevalence of fin erosion and a 28% (14/50)
      prevalence of abnormal (shortened, clubbed, or missing) barbels. Fin erosion was
      not observed in the other collections, and only 10% (5/50) of the Furnace Creek
      fish had abnormal barbels (p < 0.001 for both lesions). There were statistically
      significant differences in mean EROD activity, with levels in Furnace Creek and
      Back River fish approximately twice that found in Tuckahoe River fish. There were
      also significant differences in mean benzo(a)pyrene-like bile metabolite
      concentrations: the lowest mean was in the Tuckahoe River fish, 8 times higher in
      Furnace Creek fish, and 13 times higher in Back River fish. Of the 3 groups, the
      Back River bullheads appear to be most adversely affected by contaminant exposure
      because they had the highest prevalence of liver tumors, fin erosion, and
      abnormal barbels.

PMID- 15253048
TI  - Comparison of two sites in Mobile Bay using in vivo biomarkers in largemouth
      bass, sediment bioassays, and sediment contaminant analysis.
AB  - This research addresses whether chemical contaminants are having a biologically
      measurable effect on largemouth bass (Micropterus salmoides), an important fish
      species in the Mobile Bay National Estuary. Bass and sediment samples were
      collected in September 2001 from Big Bateau and D'Olive Bays; the latter has been
      suggested to be an environmentally impacted site. There was a significant
      difference in the age distribution of bass collected from the two sites. However,
      none of the animals showed any evidence of reproductive activity or had mature
      gametes. The age and gonadosomatic index were greater in animals collected from
      the Bateau site. Fish liver microsome ethoxyresorufin-O-deethylase (EROD)
      activities (elevated in the presence of CYP1A-inducing contaminants) were not
      significantly different between sites but were significantly higher in older
      bass. Plasma steroid concentrations in younger animals (less than 1 year old)
      tended to be higher and more variable than the concentrations found in older
      animals. Once the significant effects of age on plasma steroid concentrations
      were removed, an analysis of the residual change in steroids revealed no
      differences in testosterone or estradiol between animals collected at the two
      sites. Sediments were collected for chemical extraction and analysis in two
      bioassays: the H4IIE rat hepatoma EROD assay and the yeast estrogen screen (YES
      assay). The H4IIE bioassay indicated the presence of sediment BaP induction
      equivalents between 72 and 320 ng/g, whereas the YES assay indicated that potent
      estrogenic substances were not present in the sediment samples. The H4IIE
      bioassay results were higher for D'Olive samples, which was consistent with
      higher PAH concentrations in those sediments. Taken together the biomarkers and
      chemical analysis suggested generally low organic contamination at these two
      sites.

PMID- 15253050
TI  - Effects of multiple routes of cadmium exposure on the hibernation success of the
      American toad (Bufo americanus).
AB  - The effects of multiple routes of cadmium exposure on juvenile American toads
      (Bufo americanus) were evaluated using environmentally relevant concentrations.
      During or after exposure, toads were individually hibernated for 172 days at
      approximately 4degreesC. The following experiments were conducted: (1) dermal
      exposure (hibernation in soil contaminated with up to 120 microg Cd/g (dry
      weight)); (2) injection exposure (single injection with cadmium to achieve a
      maximum whole-body nominal concentration of 3 microg Cd/g (wet weight) 12 days
      before hibernation in uncontaminated soil); and, (3) oral exposure (feeding with
      mealworms containing < or =16 microg Cd/g (dry weight) for 50 days before
      hibernation in uncontaminated soil). We hypothesized that sublethal levels of
      cadmium would become lethal during hibernation because of combined chemical and
      cold stress. No prehibernation mortality occurred in the injection and oral
      exposure studies. There was a significant treatment effect on whole-body cadmium
      concentration in toads orally or dermally exposed and on percent of cadmium
      retention in toads orally exposed. There was also a trend of increased time-to
      burrowing and more toads partially buried with greater cadmium concentration in
      the dermal study, which indicated avoidance. In all 3 experiments, no significant
      differences were found among cadmium treatments in hibernation survival, percent
      of mass loss, or locomotor performance. However, toads fed mealworms averaging
      4.7 microg Cd/g (dry weight) had only 56% survival compared with 100% survival
      for controls. Although our results suggest that environmentally relevant levels
      of cadmium do not pose a great risk to American toads, factors such as soil type
      or prey species may increase cadmium bioavailability, and other amphibian species
      may be more sensitive to cadmium than B. americanus.

PMID- 15253049
TI  - Reproductive assessment of Japanese medaka (Oryzias latipes) following a four
      week fluoxetine (SSRI) exposure.
AB  - The occurrence of environmental pharmaceutical products has recently received
      considerable attention, but impacts on the aquatic environment are largely
      unknown. Fluoxetine is a widely prescribed antidepressant and acts
      physiologically as a selective serotonin reuptake inhibitor (SSRI). To determine
      its potential to disrupt teleost reproductive function, Japanese medaka (Oryzias
      latipes) were exposed to fluoxetine at aqueous nominal concentrations of 0, 0.1,
      0.5, 1 and 5 microg/L for 4 weeks. The last 14 days of this exposure included a
      reproductive assessment in which no significant changes were observed in egg
      production, rate of fertilization and spawning, or hatching success of fertilized
      eggs. A low incidence (1.97-2.53%; 4.02-5.16-fold greater than controls) of
      developmental abnormalities was observed in offspring from all fluoxetine
      treatments. Adult gonadal somatic index, hepatic vitellogenin, and ex vivo
      gonadal steroidogenesis were also unaffected. Circulating plasma estradiol levels
      in females were significantly increased by 0.1 and 0.5 microg/L treatments. Our
      study provides novel information on fish biochemical, physiological, and
      reproduction responses to environmentally realistic fluoxetine concentrations.

PMID- 15253051
TI  - Effects of vinclozolin on spermatogenesis and reproductive success in the
      Japanese quail (Coturnix coturnix japonica).
AB  - In a one-generation reproduction study, the major agricultural fungicide
      vinclozolin was administered to adult Japanese quail for a period of 6 weeks at
      dietary levels of 125 and 500 ppm. Fertility and reproductive performance were
      not affected up to the highest concentration, although the examination of
      additional endpoints in the drakes (spermatid count, histology of the testis)
      provided some evidence of an inhibition of spermatogenesis at both dietary
      concentrations. Likewise, there were no indications of systemic toxicity in the
      adult birds. Plasma hormone concentrations (estradiol, testosterone,
      progesterone, T3, and T4) showed a large interindividual variance but treatment
      related differences between the groups could not be established. There were no
      clear-cut indications of antiandrogenic effects in quail, although a limited
      transfer of the test substance into the eggs was proven.

PMID- 15253053
TI  - Avian mortality events in the United States caused by anticholinesterase
      pesticides: a retrospective summary of National Wildlife Health Center records
      from 1980 to 2000.
AB  - We reviewed the U.S. Geological Survey National Wildlife Health Center (NWHC)
      mortality database from 1980 to 2000 to identify cases of poisoning caused by
      organophosphorus and carbamate pesticides. From the 35,022 cases from which one
      or more avian carcasses were submitted to the NWHC for necropsy, we identified
      335 mortality events attributed to anticholinesterase poisoning, 119 of which
      have been included in earlier reports. Poisoning events were classified as
      confirmed (n = 205) when supported by findings of > or =50% inhibition of
      cholinesterase (ChE) activity in brain tissue and the detection of a specific
      pesticide in the gastrointestinal contents of one or more carcasses. Suspected
      poisonings (n = 130) were defined as cases where brain ChE activity was > or =50%
      inhibited or a specific pesticide was identified in gastrointestinal contents.
      The 335 avian mortality events occurred in 42 states. Washington, Virginia, and
      Ohio had the highest frequency of events, with 24 (7.2%), 21 (6.3%), and 20
      (6.0%) events, respectively. A total of 8877 carcasses of 103 avian species in 12
      orders was recovered. Because carcass counts underestimate total mortality, this
      represents the minimum actual mortality. Of 24 different pesticides identified,
      the most frequent were famphur (n = 59: 18%), carbofuran (n = 52; 15%), diazinon
      (n = 40; 12%), and fenthion (n = 17; 5.1%). Falconiformes were reported killed
      most frequently (49% of all die-offs) but Anseriformes were found dead in the
      greatest numbers (64% of 8877 found dead). The majority of birds reported killed
      by famphur were Passeriformes and Falconiformes, with the latter found dead in
      90% of famphur-related poisoning events. Carbofuran and famphur were involved in
      mortality of the greatest variety of species (45 and 33, respectively). Most of
      the mortality events caused by diazinon involved waterfowl.

PMID- 15253052
TI  - Phosphorus amendment reduces bioavailability of lead to mallards ingesting
      contaminated sediments.
AB  - Lead poisoning of waterfowl has been reported for decades in the Coeur d'Alene
      River Basin in Idaho as a result of the ingestion of lead-contaminated sediments.
      We conducted a study to determine whether the addition of phosphoric acid to
      sediments would reduce the bioavailability of lead to mallards (Anas
      platyrhynchos). When sediments were amended with 1% phosphorus under laboratory
      conditions, and diets containing 12% amended sediment were fed to mallards,
      reductions in tissue lead were 43% in blood, 41% in liver, and 59% in kidney with
      sediment containing about 4,520 microg/g lead on a dry-weight basis and 41, 30,
      and 57% with sediment containing about 6,990 microg/g lead. When sediments were
      treated with phosphorus and left to age for about 5 months in the field,
      reductions in lead were 56% in blood, 54% in liver, and 66% in kidney at one site
      with about 5,390 microg/g lead and 64, 57, and 77% at a second site with about
      6,990 microg/g lead. In the field, the inability to mix the phosphoric acid
      uniformly and deeply enough into the sediment may have resulted in more than 1%
      phosphorus being added to the sediment. Although both lab and field amendments of
      phosphorus substantially reduced the bioavailability of lead, lead concentrations
      in the tissues of mallards fed the amended sediments were still above those
      believed to be harmful to waterfowl. Based on earlier studies of sediment
      toxicity to waterfowl in the Coeur d'Alene River Basin, combined with the results
      of our amendment study, the addition of phosphoric acid as we used it might only
      significantly benefit waterfowl where sediments or soils contain less than 1,000
      2,000 microg/g lead.

PMID- 15253054
TI  - Measurement of toxaphene congeners in pooled human serum collected in three U.S.
      cities using high-resolution mass spectrometry.
AB  - Because human toxaphene exposure data are largely lacking, we surveyed human
      serum pools collected from U.S. residents to determine the feasibility of
      measuring toxaphene in human samples and to determine whether additional
      analytical requirements were needed for routine measurement of toxaphene. We
      report a method for quantification of toxaphene congeners in human serum using a
      mixed-bed gradient solid-phase extraction and analysis using gas chromatography
      high-resolution mass spectrometry with electron-impact ionization. In this
      method, we monitored low-mass fragment ions that were common to all 22 congeners.
      To verify the specific congeners detected, we further analyzed the extract using
      negative methane chemical ionization. We used this method to measure two specific
      congeners, Parlar 26 and 50, at concentrations ranging from about 3 to 30 pg/ml
      (0.7-7 ng/g lipid) in pooled human serum collected in Atlanta, Chicago, and
      Cincinnati. We identified several analytical parameters that must be strengthened
      to routinely measure toxaphene congeners in human samples.

PMID- 15253055
TI  - Watershed infarcts in the fetal and neonatal brainstem. An aetiology of central
      hypoventilation, dysphagia, Moibius syndrome and micrognathia.
AB  - Watershed zone infarcts of the human cerebral cortex at the overlapping junctions
      of the anterior and middle cerebral arterial territories are well known. Another
      watershed zone exists in the brainstem tegmentum, between the terminal perfusion
      zones of the paramedian penetrating and long circumferential arteries, which are
      paired segmental vessels arising from the basilar artery. The vertebrobasilar
      circulation achieves its mature configuration and caudorostral flow by 9 weeks
      gestation. Systemic hypotension and other conditions of reduced basilar perfusion
      in the fetus, either early or late in gestation, may result in symmetrical
      longitudinal columns of infarction in the midbrain and tegmentum of the pons and
      medulla oblongata and laminar necrosis of the midbrain tectum. Within this zone
      are cranial nerve nuclei III-XII, the nucleus and tractus solitarius or central
      pneumotaxic center, as well as the nucleus ambiguus and other somatic motor
      nuclei that subserve muscles of swallowing, mastication and tongue movement.
      Watershed infarcts in the human fetal and neonatal brainstem are clinically
      expressed as multiple cranial neuropathies, failure of central respiratory drive
      and apnea, dysphagia and aspiration, Mobius syndrome and Pierre Robin sequence.
      MRI is sometimes helpful, but most of the involved neuroanatomical structures are
      beneath the resolution of present imaging techniques, and the diagnosis during
      life depends upon clinical neurological examination of the neonate, sometimes
      supported by evoked potential studies. Postmortem examination confirms the
      diagnosis and dates the lesions, but also contributes to better understand
      transient or persistent vascular insufficiencies in the fetal and neonatal
      brainstem.

PMID- 15253057
TI  - Hereditary sensory neuropathy with spastic paraplegia.
AB  - We report the case of a 4-year-old boy with hereditary sensory neuropathy
      manifesting as insensitivity to pain in all four limbs and associated with
      spastic paraplegia. The patient was referred with multiple injuries to his
      fingers suggestive of self-mutilation and attributed to psychiatric disturbance.
      Clinical examination corrected the diagnosis by revealing insensitivity to pain
      in all four limbs, associated with spastic paraplegia. The histamine test
      reaction was positive, nerve biopsy and electrophysiological investigations
      confirmed sensory nerve involvement and the diagnosis of hereditary sensory
      neuropathy. Classification and treatment of such rare diseases is difficult and a
      multidisciplinary approach is often necessary.

PMID- 15253056
TI  - Clinical and epidemiological characteristics of subacute sclerosing
      panencephalitis in Bulgaria during the past 25 years (1978-2002).
AB  - The aims of the present study are to establish the subacute sclerosing
      panencephalitis (SSPE) incidence in Bulgaria for the 25-year period 1978-2002; to
      analyze the SSPE incidence prior to, and in the period of, routine measles
      immunization; and, to analyze the clinical characteristics of SSPE. SSPE was
      diagnosed in a total of 40 children; 28 of were diagnosed between 1978 and 1984,
      and 12 between 1995 and 2002. Thirty-eight cases (95%) were non-immunized and
      have had an early measles infection (mean age 16 months). The SSPE onset occurred
      primarily between 8 and 11 years of age (52.5%) with a mean latent period of
      about 7 years after the measles infection. After the 10-year disease-free period
      (1985-1994), the SSPE incidence increased between 1995 and 2002 because of the
      1991-1992 measles epidemic. During the period 1995-2002 children with earlier
      measles infection and earlier SSPE onset predominated, compared to the period
      1978-1984. The initial clinical manifestations included intellectual
      deterioration in 35%, extrapyramidal hyperkinesias in 29%, epileptic seizures in
      15%, hemiparesis in 10%, and visual disturbances in 10% of the cases. Nine
      children (22.5%) demonstrated an atypical onset. A rapidly progressive course was
      observed in 4 children (10%) and a chronic progressive course with
      pseudoremissions over 2 years-in 8 cases (20%). Our analysis of the SSPE
      incidence in Bulgaria for the 25-year period (1978-2002) supports the importance
      of early measles infection as a crucial risk factor for this persistent
      neuroinfection. Moreover, it confirms the role of routine measles immunization in
      SSPE prevention.

PMID- 15253058
TI  - Neuronal ceroid lipofuscinoses (NCL).

PMID- 15253059
TI  - CNS malformations: gene locations of known human mutations.

PMID- 15253060
TI  - The difficulties of diagnosing VPA-induced pancreatitis in children with severe
      motor and intellectual disabilities.

PMID- 15253061
TI  - Managing mental health service provision in the decentralized, multi-layered
      health and social care system of Germany.
AB  - BACKGROUND: The effective coordination of mental health service provision is a
      requirement for successfully reforming mental health care from a hospital-focused
      system towards a more decentralized, community-oriented one. Implementing such
      coordination is particularly challenging in a decentralized, multi-layered health
      and social care system such as exists in Germany. AIM OF THE STUDY: (i) To
      investigate the coordination and planning of mental health service provision
      performed at and between the local, Lander and federal political levels in
      Germany; (ii) to outline the disparities in coordination and planning of mental
      health service provision that exist between the different political levels and
      locate key-authorities; (iii) to determine whether a decentralized, multi-layered
      health and social system such as Germany's allows for adequate coordination.
      METHOD: (i) Analysis of mental health legislation and policy documents; (ii)
      guided interviews with officers and consultants of the government units
      responsible for mental health affairs of the 16 Lander and the federal Ministry
      of Health and Social Security; (iii) submission of results to the interviewed
      experts for verification. RESULTS: Multi-professional boards and posts for
      coordinating and planning mental health services are widely implemented on local
      state and federal level in Germany. Most of them operate without being required
      by legislation. The sickness and pension funds are represented in less than half
      of the boards on state level. Boards on local and on state level are mainly
      concerned with coordinating social mental health care and have little influence
      on medical mental health care. Mental health policy documents exist federally and
      in most Lander. All but one of the mental health legislations of the Lander
      (present in 12 out of the 16 Lander) also considers regulations concerning
      coordinating and planning mental heath services. The key-authorities for mental
      health policy, legislation and service implementation is with the 16 Lander. The
      federal government however plays an important frame setting role. Actual service
      provision is a local responsibility. DISCUSSION: Since the beginning of mental
      health reforms 25 years ago and in particular in recent years, structures for the
      coordination and planning of mental health service provision have been
      established countrywide at local, Lander and federal levels. However, there are
      hardly any structures that connect the Lander and local levels and act as a
      source of independent quality assurance. The coordination boards at the Lander
      level include almost all the parties involved in mental health care, with the
      exception of sickness and pension funds that are, for the most part, absent. Thus
      the coordination boards are mainly restricted to governing social services in
      mental health care. Despite this, the countrywide establishment of diverse boards
      for the structured coordination of mental health service provision can be
      regarded in itself as a success, although little is known of the processes and
      impact of this framework. There are, however, indications that coordination is
      still restricted to the traditional interfaces and dividing lines of the mental
      health care system, which they seem unable to overcome. IMPLICATION FOR HEALTH
      POLICIES: The reform of mental health service provision towards a more community
      orientated approach requires sophisticated coordination. The countrywide
      establishment of structures for the coordination and planning of mental health
      service provision has been largely possible in Germany. It does, however, require
      further analysis, since coordination beyond the traditional boundaries seems
      unlikely. Therefore, incentives are needed in order to encourage "adequate
      coordination" as well as integration with other parts of the mental health care
      system.

PMID- 15253062
TI  - Toward a model for testing the relationship between quality of care and costs.
AB  - BACKGROUND: In mental health services research there is little empirical evidence
      to support speculation about the relationship between costs and quality. AIMS OF
      THE STUDY: The purpose of this paper is to provide a conceptual model and test
      its usefulness in determining the cost of care that meets evidence-based
      standards. METHODS: A case study of individuals treated for an acute episode of
      schizophrenia is described and a conceptual model for determining the costs of
      evidence-based care is presented. Statistical tests of difference were used to
      compare two groups, those with care that met guideline standards and those that
      did not. RESULTS: Compared to care that did not meet recommendations, evidence
      based care was cheaper. Clinical benefits to patients were the same, but those
      with poor care (higher than recommended doses of anti-psychotic medication) had
      higher treatment costs as well as more side-effects. DISCUSSION: The conceptual
      model faces many challenges in application, but shows promise as one approach to
      determining the cost of evidenced based care. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: The results support efforts to encourage clinicians to follow
      practice guidelines. IMPLICATIONS FOR HEALTH POLICIES: The growth of evidence
      based medicine must be matched by efforts to assess the costs of adherence to
      practice guidelines. The pressure of fiscal restraints needs to be balanced with
      information about what the cost will be to provide recommended treatment.
      IMPLICATIONS FOR FURTHER RESEARCH: The greatest effort needs to be in the
      conceptual development of the model so that we can confidently estimate the costs
      and effectiveness of evidence-based treatment recommendations.

PMID- 15253063
TI  - Out-of-Pocket expenditure for depression among patients attending private
      community psychiatric clinics in Pakistan.
AB  - BACKGROUND: Depression is a serious public health problem in Pakistan because of
      the disabilities it causes and the cost burden for the family. About 6% of the
      Pakistani population suffers from this illness and approximately 50% ofthose
      affected seek treatment. The health budget of the country is very low, average
      per capita income is 430 US dollars and 35% of the population falls below the
      poverty line. It follows that depression puts a heavy economic burden on its
      sufferers. AIM: The aim of this study was to estimate the economic burden on
      patients suffering from depression who were attending community psychiatry
      clinics. METHODS: This is a prevalence-based analysis of mental health care
      expenditure in a sample of 200 patients with an ICD-X diagnosis of depression.
      The patients attended four private community clinics, run on a once-a-week basis,
      with all care paid for by the patients out of pocket. A questionnaire was
      designed with a view to gathering information on out-of-pocket treatment and
      travel expenditures. The data was subjected to SPSS analysis. RESULTS: Among the
      subjects enrolled in the study (n=200), 85% were spending over Rs. 3,133 (51.40
      US dollars) per month as general expenses on health. Sixty-five percent of the
      subjects were earning below Rs. 5,000 ( 86.00 US dollars). The majority used the
      public bus for transportation, costing the family Rs. 83 (1.40 US dollars) per
      trip. Laboratory investigation costs were negligible as there is a lesser
      emphasis on lab tests in psychiatry. DISCUSSION: The high cost of depression
      keeps a vast majority of the population away from ongoing treatment, which
      contributes to the misery of the illness and the associated loss of productivity.
      The national budget is very low, the average income for the majority is far from
      satisfactory, and though partial support from charitable organizations, public
      sector hospitals, insurance cover and medical facilities is available, the
      majority of needs are unmet. It is essential to increase the health budget and
      enhance efforts toward preventive strategies. Further research on health
      economics is needed along with an appropriate government database.

PMID- 15253064
TI  - Coping with disasters: estimation of additional capacity of the mental health
      sector to meet extended service demands.
AB  - BACKGROUND: The September 11th disaster in New York City resulted in an increase
      in mental health service delivery as a vast network of providers responded to the
      urgent needs of those impacted by the tragedy. Estimates of current capacity,
      potential additional capacity to deliver services and of potential shortfall
      within the mental health sector are needed pieces of information for planning the
      responses to future disasters. AIMS OF THE STUDY: Using New York State data, to
      determine the distribution of clinical service delivery rates among programs and
      to examine an explanatory model of observed variation; to estimate potential
      additional capacity in the mental health sector; and to estimate shortfall based
      on this capacity and data from studies on the need and use of services post
      September 11th METHODS: Empirical distributions of weekly clinical service
      delivery rates in programs likely to be used by persons with post disaster mental
      health problems were obtained from available data. Three regression models were
      fit to explain rate variation in terms of unmodifiable program characteristics
      likely to impact the rates. We argue that rates could not be easily increased if
      any of the models had good explanatory power, and could be increased if it did
      not. All models had poor fit. We then assumed that the median and 75th percentile
      of the clinical service delivery rates were candidates for the minimum production
      capability of a clinician. The service rates of those clinicians whose rates fell
      below these quartiles were increased to the quartile value to yield estimates of
      potential additional capacity. These were used along with data on clinical need
      to estimate shortfall. RESULTS: There is substantial variation in clinical
      service delivery rates within impact regions and among programs serving different
      age populations. The estimate of the percent increase in services overall based
      on the median is 12% and based on the 75th percentile is 27%. Using an estimate
      of need of.03 suggested by available data, and a range of services (1-10) that
      might be required in a six month period, shortfall estimates based on the median
      ranged between 22-92% and for the 75th percentile from no shortfall to 86%. A
      less conservative estimate of need of.05 produces median shortfall ranging
      between 59-96% and for the 75th percentile between 10-91%. LIMITATIONS: While the
      program descriptor variables used in the explanatory model of rates were those
      most likely to impact rates, explanatory power of the model might have increased
      if other characteristics that are not modifiable had been included. In this case,
      the assumption that service production can be increased is called into question.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: In the first six months post
      September 11th, in New York State (NYS) 250,000 persons received crisis
      counseling through Project Liberty. In 1999, NYS served approximately that same
      number in mental health clinic programs during the entire year. The estimates of
      this study suggest that additional funding and personnel are needed to provide
      mental health services in the event of a major disaster. IMPLICATIONS FOR HEALTH
      POLICIES: A disaster plan is needed to coordinate the use of current and
      additional personnel including mental health resources from other sources and
      sectors.

PMID- 15253065
TI  - Making sense of alcohol policies on youth self-destructive behavior as part of
      suicide.

PMID- 15253066
TI  - [Will epistemology be taught in professional education?].

PMID- 15253067
TI  - [Identity and daily demands for respect].

PMID- 15253068
TI  - [Resilience in care situations: theoretical and clinical approach].

PMID- 15253069
TI  - [Concept of compliance: analysis and example related to oral contraception].
AB  - Compliance is a frequently used concept within the field of health science.
      However there is not that much literature in nursing science particularly related
      to oral contraception. This text analyses compliance by the way of oral
      contraception according to Walker and Avant concept analysis model. Being the
      contraceptive way most used by women, it appears relevant to document this
      concept to enlighten nursing practice domain.

PMID- 15253070
TI  - [Intervention to promote recognition of the rights of families of an elderly
      relative with dementia living in a long-term care facility].
AB  - The rights of families of an institutionalized elderly relative with dementia
      have yet to be recognized. The results of our pilot study based on a
      participatory approach show, among other things, that family caregivers, women
      for the most part, have little input in the decisions regarding their relative's
      care and are uneasy to express their opinions to health care staff. As part of
      the pilot study, caregivers developed a group intervention program entitled
      "Taking Care of Myself" geared, among other things, towards increasing their
      competence in expressing their viewpoint to health care staff and in taking part
      in care-related decisions. According to an efficacy study conducted after the
      pilot study, the program produced successful outcomes in terms of caregiver
      competence in dealing with the health care staff and of perceived challenge of
      the caregiver situation. Recommendations are made aimed at giving caregivers
      recognition, that is their due.

PMID- 15253071
TI  - [Management and quality: in search of nursing].
AB  - Quality management involves everyone in the hospital to a different degree. The
      head-nurses are key elements for the realization of these programs. Throughout
      this discussion regarding management, this article explores the links between
      quality management and nursing. The interviews conducted show that management has
      over-invested in quality. Therefore it will respond to problems concerning work
      organization and will also allow a professional acknowledgement. The analysis
      confirms that the quality values come before that of a pragmatic conception of
      health care based on a disjunctive viewpoint, both linear and timeless.
      Furthermore, because nursing is not considered as a discipline, quality
      healthcare remains undefined. The recommendations focus on the manager's role and
      particularity on the definition of the principal problems of different services.

PMID- 15253072
TI  - [Reflections on an appropriation evaluation of the professional role's ethical
      dimensions].

PMID- 15253073
TI  - [Ethical behavior of nurses in their practices and in clinical medical research,.
      Part 1].
AB  - Providing high-quality nursing care implies to answer different questions
      pertaining to either technical or ethical features. Among these questions, two
      are studied more in-depth in the present paper. What is the ethical behaviour of
      French nurses when facing difficult clinical situations and how are they dealing
      with questions arising when clinical investigations are performed (both those
      directed by physicians but also nursing-led research). In this country, indeed,
      significant pressure from both court judgements and changes in the law now
      requires caregivers (and particularly nurses) to participate more actively in
      clinical decisions where an ethical dilemma arises. Have French nurses acquired
      the necessary tools to behave adequately in these situations and are they
      actually playing a role in daily ethical decisions? Nurses may be participating
      in physician-led research but also develop their own research. Which value do
      French nurses attribute to medical investigations and what is their perception of
      their role in physician-led research? Are they willing to lead their own research
      and what are the main barriers limiting their action? Two surveys performed at a
      two-year interval in Teaching Hospitals affiliated to the University of Paris and
      using a similar questionnaire were used to provide answers to these questions.

PMID- 15253074
TI  - [Ethical behavior of nurses in their practices and in clinical medical research.
      Part 2].

PMID- 15253076
TI  - Arthroscopic reattachment of osteochondritis dissecans lesions using resorbable
      polydioxanone pins.
AB  - REASONS FOR PERFORMING STUDY: Debridement of osteochondritis dissecans (OCD)
      cartilage lesions results in fibrocartilage and imperfect hyaline repair tissue,
      and forms a permanent irregularity to the subchondral bone plate. OBJECTIVE: To
      evaluate the clinical, radiographic and outcome effects of OCD cartilage flap
      reattachment for select lesions as an alternative to OCD debridement. HYPOTHESIS:
      Separated cartilage flaps resulting from OCD lesions may be re-incorporated into
      the hyaline cartilage surface by reattachment rather than debridement and
      removal. METHODS: Resorbable polydioxanone pins were used to reattach OCD flap
      lesions in 16 joints of 12 horses. Criteria for attachment, rather than removal,
      included an unmineralised cartilage flap on preoperative radiographs and a
      relatively smooth surface with some residual perimeter attachment at surgery.
      RESULTS: There were 12 subjects, 6 males and 6 females, 7 Thoroughbred or
      Standardbred weanlings, 3 Warmbloods, 1 Arabian and 1 Quarter Horse, mean age at
      surgery 6.8 months. All horses had effusion of the affected femoropatellar joint
      (n = 9), tarsocrural joint (n = 1) or fetlock (n = 2). Radiographic lesions
      varied in length between 1.8-6.3 cm; reattachment was used in 16 of 18 affected
      joints and the OCD cartilage was not satisfactory for salvage in 2 stifles.
      Number of pins required was 2-10. One horse was subjected to euthanasia due to a
      tendon laceration 8 weeks after surgery; of the remaining 11 horses, mean
      duration of follow-up was 3.9 years (range 4 months-8 years). Nine of these were
      sound and had entered work, while 2 were sound but remained unbroken 4 and 6
      months post operatively, respectively. Radiographic resolution of the OCD lesion
      occurred in 14 of 16 pinned joints in the 9 horses with long-term follow-up. The
      2 remaining joints had a 3 and a 5 mm mineralised flap in the original defect
      sites. CONCLUSIONS: This study indicated cartilage flap reattachment was an
      alternative to removal in selected OCD lesions. POTENTIAL RELEVANCE: Relatively
      smooth OCD cartilage flaps may be salvaged by reattachment and can result in
      normal radiographic subchondral contour and a high likelihood of athletic
      performance. Further case numbers are required to determine which lesions are too
      irregular or contain too much mineral for effective incorporation after
      reattachment.

PMID- 15253075
TI  - Prevention of ischaemia-induced small intestinal adhesions in foals.
AB  - REASONS FOR PERFORMING STUDY: Treatments addressing variously theorised
      pathophysiological mechanisms of small intestinal adhesions have been reported.
      This study applied those classes of treatments to the most clinically relevant
      aetiology of post operative adhesions. HYPOTHESIS: Treatments addressing the
      pathophysiology of ischaemia-reperfusion induced adhesions would accordingly
      reduce the incidence of adhesions from this model. METHODS: Four classes of
      treatments were administered for 72 h to 16 foals subjected to complete ischaemia
      followed by reperfusion to create peritoneal adhesions. These groups were: 1) FPG
      group--flunixin meglumine (1.1 mg/kg bwt i.v., divided q.i.d.), potassium
      penicillin G (22,000 iu/kg bwt i.v., q.i.d.) and gentamicin (2.2 mg/kg bwt i.v.,
      t.i.d.); 2) HEP group--heparin (80 iu/kg bwt subcut., b.i.d.); 3) DMSO group-
      dimethylsulphoxide (DMSO) (20 mg/kg bwt [diluted in 500 ml normal saline] i.v.,
      b.i.d.); and 4) SCMC group--sodium carboxymethylcellulose (500 ml 3% sterile
      solution intraperitoneally, administered only at the beginning of surgery).
      RESULTS: Post operative intestinal obstruction did not occur in any foal. After
      10 days, necropsy revealed bowel-to-bowel adhesions in none of the FPG or DMSO
      groups, in 2/4 of the SCMC group, in 3/4 of the HEP group and 5/6 foals subjected
      to the procedure without treatment (UIR group). CONCLUSIONS: Inhibition of the
      inflammation associated with ischaemia and reperfusion in foals treated with FPG
      or DMSO decreased small intestinal adhesions in foals. POTENTIAL RELEVANCE:
      Although anti-inflammatory therapy was shown to eliminate bowel-bowel adhesions
      in this controlled study, it must be remembered that clinical cases are without
      control. These therapies are advised to improve the result but are unlikely to
      eliminate the problem.

PMID- 15253077
TI  - Whip use and race progress are associated with horse falls in hurdle and
      steeplechase racing in the UK.
AB  - REASONS FOR PERFORMING STUDY: Falls during racing present a risk of injury to
      both horse and jockey and a risk of fatality to horses. OBJECTIVES: To use video
      recordings of races to describe the circumstances surrounding horse falls at
      hurdle and steeplechase fences and to identify and quantify within-race risk
      factors for horse falls in National Hunt racing in the UK. METHODS: A
      retrospective, matched, nested case-control study using video recordings of races
      was conducted on 6 UK racecourses. Cases and controls were matched on both race
      type and jump number at which the fall occurred. Conditional logistic regression
      analysis was used to examine the univariable and multivariable relationship
      between predictor variables and the risk of falling. RESULTS: The risk of falling
      was significantly associated with whip use and race progress. Horses which were
      being whipped and progressing through the race were at greater than 7 times the
      risk of falling compared to horses which were not being whipped and which had no
      change in position or lost position through the field. CONCLUSIONS: This study
      has identified whip use and the position of the horse with respect to others in
      the field as potential risk factors for horse falls. POTENTIAL RELEVANCE: If
      these findings are confirmed by the use of intervention trials (e.g. with whip
      free or restricted whip use races), modifications could be introduced which would
      reduce the frequency of horse falls, leading to improved equine welfare.

PMID- 15253078
TI  - Nutritional and clinicopathological effects of post operative parenteral
      nutrition following small intestinal resection and anastomosis in the mature
      horse.
AB  - REASONS FOR PERFORMING STUDY: There is an absence of data describing the
      nutritional requirements and nutritional status of horses following surgery for
      colic; furthermore, the potential effect of parenteral nutrition (PN) on
      improving nutritional status in such cases is unknown. HYPOTHESIS: Post operative
      colic cases suffer from a potentially detrimental negative energy balance and the
      PN formulation developed in this study would lead to clinicopathologically
      detectable improvements in the subjects' nutritional status. METHODS: Several
      clinicopathological variables, some known to be associated with nutritional
      status, were compared in 2 groups of horses in the post operative period
      following colic surgery; Group N (n = 15) were treated with PN and Group C (n =
      15) were starved routinely. RESULTS: Group N had significantly lower serum
      concentrations of triglycerides, total bilirubin, albumin and urea and
      significantly higher serum concentrations of glucose and insulin compared with
      Group C in the post operative period. CONCLUSIONS: The control group of horses
      demonstrated significant clinicopathological evidence of starvation and the
      described PN protocol resulted in a demonstrably improved nutritional status in
      the treated horses. POTENTIAL RELEVANCE: Further study is required to investigate
      clinical benefits and possible harmful side effects of post operative parenteral
      nutrition before the technique can be advocated for widespread use in practice.

PMID- 15253079
TI  - Polymyxin B protects horses against induced endotoxaemia in vivo.
AB  - REASONS FOR PERFORMING STUDY: A safe, affordable and effective treatment for
      endotoxaemia in horses is needed in order to reduce the incidence of this
      potentially fatal condition. OBJECTIVE: To evaluate the effect of polymyxin B
      (PMB) on signs of experimentally-induced endotoxaemia. HYPOTHESIS: PMB
      ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity.
      METHODS: Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg
      bwt i.v. over 30 mins. Additionally, each group received one of the following
      i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30
      mins after endotoxin infusion; 1000 u PMB/kg bwt 30 mins prior to endotoxin
      infusion; or saline. Clinical response data and samples were collected to
      determine neutrophil count, serum tumour necrosis factor (TNF) activity, plasma
      thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to
      creatinine ratio. RESULTS: Treatment with PMB before or after administration of
      endotoxin significantly reduced fever, tachycardia and serum TNF, compared to
      horses receiving saline. The differences in response to endotoxin were greatest
      between horses that received saline vs. those that received 5000 u PMB/kg bwt
      prior to endotoxin. Urine GGT:creatinine did not change significantly.
      CONCLUSIONS AND POTENTIAL RELEVANCE: This study indicates that PMB may be a safe
      and effective treatment of endotoxaemia, even when administered after onset.
      Although nephrotoxicity was not demonstrated with this model, caution should be
      exercised when using PMB in azotaemic patients.

PMID- 15253080
TI  - Ultrasonography of the medial palmar intercarpal ligament in the Thoroughbred:
      technique and normal appearance.
AB  - REASONS FOR PERFORMING STUDY: Tearing of the medial palmar intercarpal ligament
      (MPICL) has been recognised as a cause of lameness in the Thoroughbred, but
      diagnosis is difficult due to the nonspecific clinical signs, and can be achieved
      only by performing arthroscopy on the mid carpal joint (MCJ). It would be
      beneficial to be able to image the MPICL using ultrasonography to determine
      whether pathology is present in the ligament in order to aid diagnosis and
      prognosis. OBJECTIVES: To determine whether the MPICL could be imaged using
      ultrasound from the dorsal aspect of the MCJ, and to describe the technique and
      normal ultrasonographic appearance of the ligament. METHODS: A pilot study was
      performed using 2 cadaver carpi. Each carpus in turn had the MPICL imaged
      simultaneously using arthroscopy and ultrasound, with a metallic probe positioned
      on the dorsal aspect of the ligament to highlight the position of the MPICL. Six
      further pairs of carpi had the MPICL imaged ultrasonographically followed by
      dissection of the carpus to evaluate the ligament and relate its anatomy to the
      ultrasound images. Finally, 15 Thoroughbreds with no history of lameness isolated
      to the carpus had their MPICLs assessed and measured ultrasonographically.
      RESULTS: The MPICL could be imaged via the dorsal aspect of the MCJ using
      standard ultrasound equipment. The body and division into medial and lateral
      branches could be seen as a distinct, moderately dense granular echogenic
      structure in the palmar aspect of the joint, with clearly defined margins.
      CONCLUSIONS: The normal MPICL can be imaged reliably using ultrasound in the
      Thoroughbred from the dorsal aspect of the MCJ. There is a wide range in the
      normal width of the lateral aspect of the MPICL, but there is good symmetry
      between contralateral limbs. POTENTIAL RELEVANCE: This report of the normal
      ultrasonographic appearance of the ligament will be beneficial in acting as a
      reference for the detection of pathology using ultrasound.

PMID- 15253081
TI  - Effect of anaesthesia of the palmar digital nerves on proximal interphalangeal
      joint pain in the horse.
AB  - REASONS FOR PERFORMING STUDY: Anaesthesia of the palmar digital nerves is claimed
      to attenuate lameness in some horses that are lame because of pain in the
      proximal interphalangeal (PIP) joint. OBJECTIVE: To determine the response of
      horses with pain in the PIP joint to anaesthesia of the palmar digital nerves.
      METHODS: Horses were video recorded trotting before and after induction of pain
      in the PIP joint and 10 mins after anaesthesia of the palmar digital nerves. The
      palmar digital nerves were anaesthetised 3 times at different sites, and the
      video recorded gaits were scored subjectively. RESULTS: The median lameness score
      of gaits after administration of 2% mepivacaine 1 cm proximal to the cartilages
      of the foot was not significantly different from the median lameness score before
      anaesthesia of the palmar digital nerves (P > or = 0.05), although that of 1 of 6
      horses improved markedly. The median lameness score was significantly (P < or =
      0.05) improved after mepivacaine was administered 2 and 3 cm proximal to the
      cartilages of the foot. CONCLUSIONS: The PIP joint is unlikely to be
      anaesthetised when the palmar digital nerves are anaesthetised at the proximal
      margin of the cartilages of the foot. POTENTIAL RELEVANCE: Pain within the PIP
      joint cannot be excluded as a cause of lameness when lameness is attenuated by
      anaesthesia of the palmar digital nerves at any site proximal to the proximal
      margin of the cartilages of the foot.

PMID- 15253082
TI  - Medical management of superficial digital flexor tendonitis: a comparative study
      in 219 horses (1992-2000).
AB  - REASONS FOR PERFORMING STUDY: There is a lack of long-term follow-up data for
      outcome of medical treatment of superficial digital flexor (SDF) tendonitis.
      OBJECTIVES: To determine whether intralesional injection of hyaluronan, beta
      aminoproprionitrile fumarate (BAPN) or polysulphated glycosaminoglycans (PSGAG)
      or systemic administration of PSGAG yielded better results than a controlled
      exercise programme alone in the management of SDF tendonitis, with a minimum
      follow-up period of 2 years after resumption of full work; and to determine
      whether reinjury rate was related to sports discipline and whether fibre
      alignment score (FAS) at 4 months could predict outcome. METHODS: In Study 1, 50
      horses were managed by controlled exercise alone (Group A), 50 were treated with
      intralesional injection of hyaluronan (Group B), 20 received intralesional and
      systemic treatment with PSGAG (Group Ci) and 30 received systemic treatment with
      PSGAG (Group Cii). Horses in Groups B, Ci and Cii followed the same controlled
      exercise programme as Group A. In Study 2, 69 horses (Group D) were treated by
      intralesional injection of BAPN and followed a modified controlled exercise
      programme. Horses were re-examined clinically and ultrasonographically at
      intervals. Follow-up data were obtained for horses 2 years after resuming full
      work and for up to 6 years. RESULTS: There was no significant difference in
      reinjury rate of the treated limb(s) between Groups A, B, Ci and Cii (42.5-44.4%)
      (P>0.9). The reinjury rate (16%) in the treated limb(s) in Group D was
      significantly lower than in the other groups (P<0.001). However, when injury rate
      of the uninjured limb was considered, the results were similar to Study 1. In
      Study 2, the FAS at 4 months after treatment was a good predictor of outcome
      (P<0.001). Reinjury rates for different disciplines were similar in the 2
      studies, with the risk of reinjury ascending from showjumpers to event horses to
      National Hunt and flat racehorses. CONCLUSIONS: Treatment with BAPN reduced the
      risk of reinjury in the treated limb, although the overall rate of subsequent
      injury was not affected. FAS at 4 months after treatment is a good predictor of
      outcome in the treated limb(s). POTENTIAL RELEVANCE: This study provides long
      term follow-up data in horses from a variety of sports disciplines that can be
      used to provide prognostic information.

PMID- 15253083
TI  - Effect of laryngoplasty on respiratory noise reduction in horses with laryngeal
      hemiplegia.
AB  - REASONS FOR PERFORMING STUDY: Laryngoplasty is the technique of choice for
      treatment of laryngeal hemiplegia, with the aim of improving airway function
      and/or eliminating respiratory noise. However, there are no quantitative data in
      the literature describing the effect of laryngoplasty on upper airway noise or
      its relationship to upper airway mechanics in horses with laryngeal hemiplegia.
      OBJECTIVES: To determine whether laryngoplasty reduces respiratory noise in
      exercising horses with laryngeal hemiplegia; and to establish whether the degree
      of upper airway obstruction can be predicted by upper airway noise, or the degree
      of arytenoid abduction correlated with airway obstruction and noise production.
      METHODS: Six Standardbred horses with normal upper airways during maximal
      exercise were used. Respiratory sounds and inspiratory transupper airway pressure
      (Pui) were measured in all horses before and after induction of laryngeal
      hemiplegia and 30, 60 and 90 days after laryngoplasty. Inspiratory sound level
      (SL) and the sound intensity of the 3 inspiratory formants (F1, F2 and F3,
      respectively) were measured using a computer-based sound analysis programme. The
      degree of abduction was graded by endoscopic visualisation 1, 30, 60 and 90 days
      post operatively. Linear regression analysis was used to determine correlations
      between Pui, sound indices and grades of arytenoid abduction. RESULTS: In
      laryngeal hemiplegia-affected horses, Pui, inspiratory SL and the sound intensity
      of F1, F2 and F3 were significantly increased. At 30 days following
      laryngoplasty, the sound intensity of F1 and Pui returned to baseline values. The
      sound intensities of F2, F3 and SL were significantly improved from laryngeal
      hemiplegia values at 30 days post operatively, but did not return to baseline at
      any measurement period. Sound level, F2 and F3 were significantly correlated with
      Pui (P<0.05), but the correlations were weak (r2 = 0.26, 035 and 0.40,
      respectively). Grade of abduction and F2 were positively and significantly
      correlated (P<0.006, r2 = 0.76). Grade of arytenoid abduction and Pui were not
      correlated (P = 0.12). CONCLUSIONS: Laryngoplasty reduced inspiratory noise in
      laryngeal hemiplegia-affected horses by 30 days following surgery, but did not
      return it to baseline values. While upper airway noise and Pui were correlated,
      this relationship was insufficiently strong to predict Pui from noise in
      individual animals. The degree of arytenoid abduction was not correlated with
      Pui, but was positively correlated with noise production. POTENTIAL RELEVANCE:
      Laryngoplasty reduces upper airway noise in horses with laryngeal hemiplegia, but
      is not as effective as bilateral ventriculocordectomy in this regard, although
      respiratory noise reduction occurs more rapidly than with bilateral
      ventriculocordectomy. Residual noise during exercise cannot be used as a
      predictor of improvement in upper airway function in individual horses following
      laryngoplasty. The degree of arytenoid abduction obtained following surgery does
      not affect upper airway flow mechanics. Interestingly, we found that the greater
      the arytenoid abduction, the louder the respiratory noise.

PMID- 15253084
TI  - Efficacy of oral and intravenous dexamethasone in horses with recurrent airway
      obstruction.
AB  - REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the
      treatment of recurrent airway obstruction (RAO) has been documented, the speed of
      onset of effect and duration of action are unknown, as is the efficacy of orally
      administered dexamethasone with or without fasting. OBJECTIVES: To document the
      time of onset of effect and duration of action of a dexamethasone solution i.v.
      or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected
      horses with airway obstruction in a crossover design experiment that compared the
      effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function
      over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the
      effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg
      bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with
      fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung
      function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was
      effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior
      to feeding. The duration of effect was, for all dexamethasone treatments,
      statistically significant for 30 h when compared to saline and tended to have a
      longer duration of effect when used orally. Dexamethasone per os at a dose of
      0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a
      dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding
      decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a
      rapid onset of action in RAO-affected horses. Oral administration of a
      bioequivalent dose of the same solution to fasted horses is as effective as i.v.
      administration and tends to have longer duration of action. Fasting horses before
      oral administration of dexamethasone improves the efficacy of treatment.
      POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone
      solution intended for i.v. use provides an effective treatment for RAO-affected
      animals.

PMID- 15253085
TI  - Relationship of foot conformation and force applied to the navicular bone of
      sound horses at the trot.
AB  - REASONS FOR PERFORMING STUDY: Collapsed heels conformation has been implicated as
      causing radical biomechanical alterations, predisposing horses to navicular
      disease. However, the correlation between hoof conformation and the forces
      exerted on the navicular bone has not been documented. HYPOTHESIS: The angle of
      the distal phalanx in relation to the ground is correlated to the degree of heel
      collapse and foot conformation is correlated to the compressive force exerted by
      the deep digital flexor tendon on the navicular bone. METHODS: Thirty-one shod
      Irish Draught-cross type horses in routine work and farriery care were trotted
      over a forceplate, with 3-dimensional (3D) motion analysis system. A lateromedial
      radiograph of the right fore foot was obtained for each horse, and various
      measurements taken. Correlation coefficients were determined between hoof
      conformation measurements and between each of these and the force parameters at
      the beginning (15%) of stance phase, the middle of stance (50%) and at the
      beginning of breakover (86% of stance phase). Significance was defined as P<0.05.
      RESULTS: The force exerted on the navicular bone was negatively correlated
      (P<0.05) to the angle of the distal phalanx to the ground and to the ratio
      between heel and toe height. This was attributed to a smaller extending moment at
      the distal interphalangeal joint. There was not a significant correlation between
      the angle of the distal phalanx and the degree of heel collapse, and heel
      collapse was not significantly correlated to any of the force parameters.
      CONCLUSIONS: Hoof conformation has a marked correlation to the forces applied to
      the equine foot. Heel collapse, as defined by the change in heel angle in
      relation to toe angle, appears to be an inaccurate parameter. The forces applied
      on the foot are well correlated to the changes in the ratio of heel to toe
      heights and the angles of the distal phalanx. POTENTIAL RELEVANCE: Assessment of
      hoof conformation should be judged based on these parameters, as they may have
      clinical significance, whereas parallelism of the heel and toe is of less
      importance.

PMID- 15253086
TI  - Meal size and starch content affect gastric emptying in horses.
AB  - REASONS FOR PERFORMING STUDY: Feeding practices have been associated with colic
      in horses. If meal size and composition have an effect on gastric emptying, this
      could be one of the mechanisms by which feeding practices are related to the
      occurrence of colic. OBJECTIVES: To evaluate the effect of meal size and starch
      content on solid phase gastric emptying. METHODS: Solid phase gastric emptying of
      3 different radiolabelled meals, small low-starch (SmLS), small high-starch
      (SmHS) and large high-starch (LgHS) meals, was measured in 5 horses by
      scintigraphy using 99mTc-disofenin. Data were compared among meals using
      nonlinear mixed-effects models and paired t tests. RESULTS: On a percentage
      basis, SmHS emptied significantly faster than LgHS and SmLS emptied significantly
      faster than SmHS meals. However, when meals of unequal size were compared by
      emptying rate in g/min and Kcal/min, LgHS emptied significantly faster than SmHS.
      CONCLUSIONS: Meal size and composition affect gastric emptying. POTENTIAL
      RELEVANCE: Further work needs to be performed in order to substantiate the
      possibility of a relationship between digestive functions and occurrence of colic
      and gastric ulcers.

PMID- 15253087
TI  - Radiographic evaluation of sclerosis of the third carpal bone associated with
      exercise and the development of lameness in Standardbred racehorses.
AB  - REASONS FOR PERFORMING STUDY: Sclerosis of the third carpal bone is a common
      radiographic finding in both lame and sound racehorses, but there are no
      guidelines correlating degree of sclerosis and incidence of lameness. OBJECTIVES:
      To develop a protocol for describing subchondral bone sclerosis in C3 on
      dorsoproximal-dorsodistal oblique (DPr-DDiO) radiographs of the carpus and to
      correlate these changes with exercise history and carpal lameness. METHODS: One
      hundred and six Standardbreds entering their first year of training (exercise
      group) and 7 age-matched Standardbreds at pasture (controls) were examined at
      approximately 3 month intervals over 12-18 months. Examinations consisted of
      lameness evaluation and carpal radiographs (DPr-DDiO and flexed lateromedial
      projections). A grading system (very mild, mild, moderate and severe) for C3
      sclerosis seen on the DPr-DDiO radiograph was developed that utilised a
      combination of the criteria of trabecular thickening (trabecular score; TS) and
      total percent area of the C3 radial facet affected (TAA). RESULTS: Exercise group
      horses showed significant increase in TS and TAA throughout training compared to
      control horses. Middle carpal joint lameness developed in 32/106 (30%) exercise
      group horses and none of the control horses. Incidence of middle carpal joint
      (MCJ) lameness was lower in horses with mild (2/30, 6.7%) than moderate (10/32,
      31.2%) and severe (20/44, 45.4%) sclerosis throughout training. CONCLUSIONS:
      Horses with higher grades of sclerosis, as defined by this novel grading system,
      were more likely to develop MCJ lameness at some point of training. The proposed
      grading system gave a quantitative assessment of radiographic sclerosis that
      could then be used to correlate increasing severity of sclerosis with increasing
      incidences of lameness. POTENTIAL RELEVANCE: These results serve as a basis for
      further investigation into determining the degree of C3 sclerosis at which
      pathological changes and lameness can be expected.

PMID- 15253088
TI  - Efficacy of a live equine herpesvirus-1 (EHV-1) strain C147 vaccine in foals with
      maternally-derived antibody: protection against EHV-1 infection.
AB  - REASONS FOR PERFORMING STUDY: Currently, there is no recommended
      immunoprophylaxis against febrile respiratory diseases due to equine herpesvirus
      1 (EHV-1) and -4 (EHV-4) in horses below age 5-6 months. This is because of
      interference by maternally-derived antibody (MDA) of vaccines. OBJECTIVE:
      Unweaned equine foals are an important reservoir of EHV-1 transmission;
      therefore, we experimentally assessed the efficacy of a live EHV-1 vaccine in
      foals age 1.4-3.5 months with MDA. METHODS: Following vaccination and challenge,
      parameters assessed were virus shedding in nasal mucus, leucocyte-associated
      viraemia, circulating virus neutralising antibody activity and clinical
      reactions. RESULTS: Controlled challenge showed that a single intranasal dose of
      the vaccine afforded partial but significant protection against febrile
      respiratory disease, virus shedding and viraemia due to EHV-1 infection, despite
      virus-neutralising MDA. CONCLUSIONS AND POTENTIAL RELEVANCE: The prospective
      vaccine would be a significant step forward in reducing the incidence of the
      disease caused by EHV-1 infection.

PMID- 15253089
TI  - What is the likelihood that Thoroughbred foals treated for septic arthritis will
      race?
AB  - REASONS FOR PERFORMING STUDY: Septic arthritis is a serious problem in the
      neonate, with a poor prognosis being reported for recovery. The impact of
      neonatal septic arthritis on the likelihood that Thoroughbred (TB) foals will
      start on a racecourse is not known. HYPOTHESIS: The development of septic
      arthritis in a TB foal significantly reduces the likelihood that it will race
      when compared to foals from the same dam. METHODS: Medical records of 69 foals
      treated for septic arthritis were reviewed. The dam's foaling records were
      reviewed and lifetime racing records were then retrieved for both the affected
      foals and at least one of their siblings (controls). Outcomes that were
      statistically evaluated included discharge from the hospital and whether the foal
      eventually raced. Univariate analyses of categorical variables were conducted for
      each outcome. The number of affected and unaffected foals that raced at least
      once were compared using regression analysis. Survival analysis was used to
      compare age at first race between the study and comparison groups. RESULTS: Foals
      with septic arthritis were less likely to start on a racecourse compared to
      controls (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.12-0.62, P =
      0.001), while those foals that were discharged from the hospital were also less
      likely to start on a racecourse compared to controls (OR 036; CI 0.15-0.83, P =
      0.008). The presence of multisystem disease was associated with a decreased
      likelihood of surviving to be discharged (OR 0.13; 95% CI 0.02-0.90; P = 0.005),
      but did not affect the likelihood that they would start in at least one race if
      discharged successfully (OR 0.45; 95% CI 0.04-2.81; P = 0.34) compared to the
      other foals with septic arthritis. Log-rank comparison of survival curves
      confirmed that foals discharged following treatment for septic arthritis took
      significantly longer to start in their first race compared to the sibling
      population (mean age of study group 1757 days, CI 1604-1909; mean age of sibling
      group 1273 days, CI 1197-1349; P = 0.0006). CONCLUSIONS: The development of
      septic arthritis in a TB foal significantly reduces the likelihood that it will
      start on a racecourse when compared to controls. POTENTIAL RELEVANCE: Accurate
      figures allowing a realistic assessment of the athletic future of a foal
      following treatment for septic arthritis are of significance for both owner and
      treating veterinarian.

PMID- 15253090
TI  - Posttraumatic stress disorder symptoms, physical health, and health care
      utilization 50 years after repeated exposure to a toxic gas.
AB  - The posttraumatic sequelae of contaminant exposure are a contemporary
      international concern due to the threats posed to military personnel and
      civilians by war and bioterrorism. The role of PTSD symptoms as a mediator
      between potentially traumatic toxin exposure and physical health outcomes was
      examined with structural equation modeling in a probability sample of 302 male
      World War II-era U.S. military veterans 50 years after exposure to mustard gas
      tests. Controlling for age and psychological distress, the most parsimonious
      structural model involved PTSD symptoms mediating the relationship between toxin
      exposure and physical health problems, and physical health problems mediating the
      relationship between PTSD symptoms and outpatient health care utilization.
      Implications for researchers, mental health clinicians, and health care providers
      are discussed.

PMID- 15253091
TI  - The course of PTSD symptoms among Gulf War veterans: a growth mixture modeling
      approach.
AB  - Relatively little is known about the course of PTSD symptoms over time following
      trauma exposure. Accordingly, this study utilized a specialized structural
      equation modeling approach, growth mixture modeling, to examine the trajectory of
      PTSD symptoms across three time points in a sample of Gulf War veterans (n at
      Time 1 = 2,949, n at Time 2 = 2,313, and n at Time 3 = 1,327). Results were most
      consistent with a two-group model suggesting that the course of PTSD symptoms
      following the Gulf War was best characterized by two distinct growth curves: (1)
      low levels of PTSD symptoms with little increase over time and (2) higher levels
      of initial symptoms with a significant increase over time. Thus, it appears that
      response to Gulf War experiences is not homogeneous, and that a subset of
      individuals may experience relatively more PTSD symptoms over time. In addition,
      men, Whites, those reporting more education, and those reporting less combat
      exposure had a significantly higher probability of being classified into the less
      symptomatic group.

PMID- 15253092
TI  - Adult sexual assault: prevalence, symptomatology, and sex differences in the
      general population.
AB  - The prevalence and impact of adult sexual assault (ASA) were examined in a
      stratified random sample of the general population. Among 941 participants, ASA
      was reported by 22% of women and 3.8% of men. Multivariate risk factors for ASA
      included a younger age, being female, having been divorced, sexual abuse in
      childhood, and physical assault in adulthood. Childhood sexual abuse was
      especially common among sexually assaulted men and women (61 and 59%,
      respectively). ASA victims were more symptomatic than their nonassaulted cohorts
      on all scales of the Trauma Symptom Inventory (TSI; J. Briere, 1995), despite an
      average of 14 years having passed since the assault. Assaulted men reported
      greater symptomatology than assaulted women, whereas nonassaulted men reported
      less symptomatology than nonassaulted women.

PMID- 15253093
TI  - VA practice patterns and practice guidelines for treating posttraumatic stress
      disorder.
AB  - Little is known about how recent ISTSS practice guidelines (E. B. Foa, T. M.
      Keane, & M. J. Friedman, 2000) compare with prevailing PTSD treatment practices
      for veterans. Prior to guideline dissemination, clinicians in 6 VA medical
      centers were surveyed in 1999 (n = 321) and in 2001 (n = 271) regarding their use
      of various assessment and treatment procedures. Practices most consistent with
      guideline recommendations included psychoeducation, coping skills training,
      attention to trust issues, depression and substance use screening, and
      prescribing of SSRIs, anticonvulsants, and trazodone. PTSD and trauma assessment,
      anger management, and sleep hygiene practices were provided less consistently.
      Exposure therapy was rarely used. Additional research is needed on training,
      clinical resources, and organizational factors that may influence VA
      implementation of guideline recommendations.

PMID- 15253094
TI  - Posttraumatic Stress Disorder Symptom Checklist: factor structure and English
      Spanish measurement invariance.
AB  - This study used confirmatory factor analysis to compare alternative models of the
      structure of posttraumatic distress symptoms as measured by the Posttraumatic
      Stress Disorder Checklist--Civilian version (PCL-C; F. W. Weathers, B. T. Litz,
      D. S. Herman, J. A. Huska, & T. M. Keane, 1993). Data were derived from English-
      (N = 299) and Spanish-speaking (N = 120) samples of young adult survivors of
      community violence recruited following hospitalization for physical injuries. The
      best fit to the data was a four-factor model measuring correlated dimensions of
      reexperiencing, avoidance, emotional numbing, and hyperarousal. English- and
      Spanish-language versions of the PCL-C showed general measurement equivalence.

PMID- 15253095
TI  - Characteristics and content of intrusive memories in PTSD and their changes with
      treatment.
AB  - Although intrusive reexperiencing is a core symptom of postraumatic stress
      disorder (PTSD), relatively little is known about its phenomenology. The present
      study assessed the characteristics and content of intrusive trauma memories in 22
      patients with PTSD, and followed their changes in the course of cognitive
      behavioral treatment. Patients had a small number of different intrusive memories
      (1-4, M = 2.2) that occurred in an invariable, repetitive way. The intrusions
      were distressing and had a vivid perceptual content. They appeared to the patient
      to be happening in the "here and now." With therapy, the frequency, vividness,
      distress, and nowness of the intrusions faded gradually. There was no
      exacerbation with imaginal reliving. The content of intrusions was classified by
      raters to test A. Ehlers et al.'s (2002) hypothesis that intrusive memories are
      usually of warning stimuli that signalled the moments with the greatest emotional
      impact. The results were consistent with this hypothesis.

PMID- 15253096
TI  - An experimental study of emotional responding in women with posttraumatic stress
      disorder related to interpersonal violence.
AB  - Although posttraumatic stress disorder (PTSD) is defined by the experience of
      intense negative emotions and emotional numbing (American Psychiatric
      Association, 1994), empirical study of emotional responding in PTSD has been
      limited. This study examined emotional responding among women with and without
      PTSD to positive and negative film stimuli across self-reported experience,
      facial expression, and written expression. Consistent with previous findings, no
      evidence for generalized numbing was found. In general, women with PTSD exhibited
      higher levels of negative activation and expressed more negative emotion words to
      both positive and negative film stimuli, whereas no group differences emerged in
      facial expressivity. Results are interpreted within the context of the current
      literature on emotional deficits associated with PTSD.

PMID- 15253097
TI  - A concise measure of anger in combat-related posttraumatic stress disorder.
AB  - There is a need for a brief specific measure of anger for use in assessment of
      posttraumatic mental health problems. One unpublished short scale is the
      Dimensions of Anger Reactions (DAR; R. Novaco, 1975). This study examined the
      psychometric properties of the DAR using intake and 12-month data for 192
      Australian Vietnam veterans with combat-related PTSD. Results showed the DAR to
      be unidimensional, reliable, and sensitive to change over time, and removal of
      two items improved the scale's properties. The DAR measures anger disposition
      directed towards others. Assessment of convergent validity indicated that the DAR
      primarily measures Trait Anger. Results suggest that the DAR is a
      psychometrically strong measure, potentially useful for the evaluation of anger
      in PTSD.

PMID- 15253098
TI  - Nightmares, insomnia, and sleep-disordered breathing in fire evacuees seeking
      treatment for posttraumatic sleep disturbance.
AB  - Eight months after the Cerro Grande Fire, 78 evacuees seeking treatment for
      posttraumatic sleep disturbances were assessed for chronic nightmares,
      psychophysiological insomnia, and sleep-disordered breathing symptoms. Within
      this sample, 50% of participants were tested objectively for sleep-disordered
      breathing; 95% of those tested screened positive for sleep-disordered breathing.
      Multiple regression analyses demonstrated that these three sleep disorders
      accounted for 37% of the variance in posttraumatic stress symptoms, and each
      sleep disorder was significantly and independently associated with posttraumatic
      stress symptoms severity. The only systematic variable associated with
      posttraumatic stress symptoms of avoidance was sleep-disordered breathing. The
      findings suggest that three common sleep disorders relate to posttraumatic stress
      symptoms in a more complex manner than explained by the prevailing psychiatric
      paradigm, which conceptualizes sleep disturbances in PTSD merely as secondary
      symptoms of psychiatric distress.

PMID- 15253099
TI  - Posttraumatic mental and physical health correlates of forgiveness and religious
      coping in military veterans.
AB  - This study assessed mental and physical health correlates of dispositional
      forgiveness and religious coping responses in 213 help-seeking veterans diagnosed
      with PTSD. Controlling for age, socioeconomic status, ethnicity, combat exposure,
      and hostility, the results indicated that difficulty forgiving oneself and
      negative religious coping were related to depression, anxiety, and PTSD symptom
      severity. Difficulty forgiving others was associated with depression and PTSD
      symptom severity, but not anxiety. Positive religious coping was associated with
      PTSD symptom severity in this sample. Further investigations that delineate the
      relevance of forgiveness and religious coping in PTSD may enhance current
      clinical assessment and treatment approaches.

PMID- 15253100
TI  - Emotional deficits in military-related PTSD: an investigation of content and
      process disturbances.
AB  - To expound on the nature of emotional deficits in PTSD, the current study
      investigated the relationships among emotion content and process variables and
      PTSD symptomatology in a sample of 85 veterans with military-related trauma.
      Alexithymic externally oriented thinking and negative affectivity emerged as the
      most consistent predictors of PTSD symptoms; however, depression was the only
      variable associated with emotional numbing. Theoretical and clinical implications
      of these findings are discussed, as well as future research directions including
      the collateral and clinician assessment of emotional functioning, use of other
      process measures, and inclusion of various control groups.

PMID- 15253101
TI  - Lipoprotein lipase gene polymorphisms and blood pressure levels in the Northern
      Chinese Han population.
AB  - The lipoprotein lipase (LPL) gene has been investigated extensively in linkage
      studies and in studies of its association with lipid profiles and coronary artery
      disease (CAD), and this gene has also been reported to have an association with
      hypertension. In our previous linkage study on 148 Chinese hypertensive families,
      the regions at or near the LPL gene were found to be associated with systolic
      blood pressure (SBP) and diastolic blood pressure (DBP). Thus the LPL gene is a
      logical candidate gene for involvement in the underlying cause of essential
      hypertension (EH). In the present study, we identified 22 sequence variants by
      directly sequencing 10 exons and flanking regions of the LPL gene, and
      investigated the occurrence of 3 of these variants, IVS4-214C>T, 7754C>A and
      S447X, in a case-control study including 501 normotensive (NT) subjects and 497
      EH subjects. In males, the frequencies of the genotypes of each of the 3 variants
      did not differ significantly between the NT and EH groups. Among the EH group in
      females, ANCOVA revealed no significant difference in blood pressure levels
      according to the 7754C>A genotype. However, in female, the distribution of the
      7754C>A genotype and the frequency of the A allele of 7754C>A differed
      significantly between the NT and EH groups (p=0.032 and p=0.027, respectively)
      with 0.78 (95% confidence interval (CI): 0.56 to 1.07; p=0.12) of odds ratio for
      the A allele. Moreover, haplotype analysis revealed that T-A-C and T-C-G
      haplotypes (in the order of IVS4-214C>T, 7754C>A and S447X) were statistically
      more frequent in the NT group than in the EH group in females and males,
      respectively. Our indivisual single nucleotide polymorphism (SNP) analysis did
      not provide substantial evidence of an association between polymorphisms in the
      LPL gene and hypertension status and/or blood pressure levels in this cohort, but
      the more powerful haplotypes analysis suggested an association between the LPL
      gene and hypertension.

PMID- 15253102
TI  - Comparison between cilnidipine and amlodipine besilate with respect to
      proteinuria in hypertensive patients with renal diseases.
AB  - Unlike other dihydropyridine calcium channel blockers (CCBs), cilnidipine has
      been reported to exert an N-type calcium-channel-blocking activity and to reduce
      sympathetic hyperactivity. This study compared cilnidipine and amlodipine with
      respect to their effects on renal function and proteinuria. Twenty-eight
      proteinuric hypertensive outpatients (13 men and 15 women, aged 62+/-2 years) who
      had been maintained on CCBs for more than 3 months were randomly assigned to a
      group receiving amlodipine besilate (14 patients) or a group receiving
      cilnidipine (14 patients). CCBs were increased in dosage or other drugs were
      added until blood pressure decreased below 140/90 mmHg, but no inhibitors of the
      renin-angiotensin (RA) system were added or changed in dosage. Before and at 6
      and 12 months after randomization, the concentrations of urine protein, urine
      albumin, serum and urine creatinine (Cr), and serum beta2-microglobulin were
      determined. The amlodipine group showed a significant increase in proteinuria,
      while the increase was suppressed in the cilnidipine group. The rate of increase
      in proteinuria at 12 months was 87% (95% confidence interval (CI) -10 to 184) of
      the baseline value with amlodipine and 4% (95% CI -69 to 77) of baseline with
      cilnidipine, a significant intergroup difference (p<0.05). The mean blood
      pressure remained in the 96-99 mmHg range until 12 months after randomization,
      showing no significant difference between the two groups. The cilnidipine group
      showed an increase in serum Cr levels (baseline vs. 12 months, 1.36+/-0.20 vs.
      1.50+/-0.23 mg/dl, p<0.01). Overall, an inverse correlation existed between the
      changes in Cr and proteinuria (r= -0.477, p<0.01). These results suggest that
      cilnidipine results in a greater suppression of the increase in proteinuria and
      greater reduction in glomerular filtration rate than amlodipine, and that these
      effects are similar between cilnidipine and RA inhibitors. However, additional
      large-cohort and longer-term studies will be needed to clarify whether
      cilnidipine is superior to other CCBs in maintaining renal function.

PMID- 15253103
TI  - Association of QT interval with blood pressure in 80-year-old subjects.
AB  - Few data are available on the association between the prolonged heart rate
      adjusted QT (QTc) interval and high blood pressure in elderly individuals,
      particularly in subjects over 80 years old. The aim of the present study was to
      determine the association between the QTc interval and blood pressure in 80-year
      old subjects. This study was part of the 8020 Data Bank Survey, which was
      designed to collect the baseline data of systemic and dental health conditions in
      80-year-old subjects. We studied the cross-sectional association of the QTc
      interval with blood pressure in 642 Japanese (257 men and 385 women), all 80
      years old. Mean systolic blood pressure (SBP) rose from 146.0 mmHg in the first
      quartile of QTc interval to 149.1 mmHg in the second, 154.6 mmHg in the third,
      and 152.3 mmHg in the fourth quartile (test for trend, p=0.008). Mean diastolic
      blood pressure (DBP) also rose from 76.9 mmHg in the first quartile of QTc
      interval to 77.7 mmHg in the second, 81.8 mmHg in the third, and 79.0 mmHg in the
      fourth quartile (test for trend, p=0.003). We performed multiple regression
      analysis, controlling for factors known to influence the QTc intervals-e.g., SBP,
      heart rate, sex, and left ventricular hypertrophy assessed by the voltage
      amplitudes recorded in the precordial leads of the electrocardiogram. The
      association between the QTc interval and SBP was highly statistically significant
      in all analyses. These results show that SBP by itself may influence the QTc
      interval in very old subjects.

PMID- 15253104
TI  - Sodium intake and cardiac sympatho-vagal balance in young men with high blood
      pressure.
AB  - We have previously reported that a high sodium intake increases sleep-time blood
      pressure (BP) in young men. However, there are cases in which this relation does
      not apply. To account for them, we investigated the relation between sodium
      intake and cardiac sympatho-vagal balance (SVB) in young men with high BP. Sodium
      intake was estimated from the amount of urinary sodium excretion over 1 week.
      Twenty-four-hour (24-h) urinary sodium excretion (Salt24), 24-h ambulatory BP and
      ECG were obtained on the last day of the observation period. As an index of
      sodium intake, the expression In(Salt24/Cr24) (Cr24, 24-h urinary creatinine
      excretion) was used. From power-spectral analysis of ECG-RR intervals during
      sleep, we obtained the LF/HF ratio between the low-frequency component (LF) and
      the high frequency component (HF) and used it as an index of SVB. The subjects
      were male medical students divided into a normal BP group (N-group; n=103) and a
      high BP group (H-group; n=26, 24-h BP>125/75 mmHg). Mean In(Salt24/Cr24) and
      LF/HF in the H-group were significantly higher than those in the N-group (LF/HF:
      1.86+/-0.44 [SD] vs. 1.37+/-0.30, p<0.001). The calculated discriminant function
      (D) for the H-group and N-group was D=1.6x + 5y - 11, where x is In(Salt24/Cr24)
      and y is LF/HF. This formula (D) resulted in high discriminant predictive
      accuracy (82%) between the groups. If D=0 (the value of the cut-off line
      determining separation of the groups), the relation y=-0.32x + 2.2 (negative
      relation between y and x) was obtained. These results suggest that excessive
      sodium intake in combination with accentuated SVB (LF/HF) increases BP in young
      men.

PMID- 15253105
TI  - Renal protective role of bradykinin B1 receptor in stroke-prone spontaneously
      hypertensive rats.
AB  - The kallikrein-kinin system plays important roles in blood pressure regulation,
      metabolism of electrolytes and organ protection. Although the bradykinin B2
      receptor (B2R) has been reported to be involved in most of these effects, a role
      of the bradykinin B1 receptor (B1R) has also been noted recently. The aim of this
      study was to determine the role of renal B1R in stroke-prone spontaneously
      hypertensive rats (SHR-SP). Sixteen-week-old SHR-SP and Wistar Kyoto rats (WKY)
      as a control were used in the experiments. A high level of B1R mRNA was detected
      in SHR-SP, while the expression in WKY was almost undetectable.
      Immunohistochemistry revealed a B1R protein in the renal tubules and glomeruli in
      SHR-SP. The acute injection of a B1 R agonist into SHR-SP increased urinary NOx
      excretion to a level up to 5-fold higher than that in the SHR-SP treated with
      vehicle. The infusion of B1 R antagonist for 4 weeks resulted in a significant
      elevation of blood pressure and urinary albumin excretion and a decrease in
      urinary NOx excretion in SHR-SP. The administration of B1 R antagonist resulted
      in renal interstitial and glomerular fibrosis in SHR-SP. Moreover, the
      expressions of transforming growth factor (TGF) beta1 protein and collagen III
      mRNA in SHR-SP treated with B1R antagonist were significantly higher than those
      of SHR-SP treated with a vehicle. The expression and phosphorylation of
      extracellular signal-regulated protein kinase (ERK) and p38, but not c-Jun N
      terminal kinase (JNK), were significantly increased in the SHR-SP treated with
      B1R antagonist. These results indicated that renal B1R might be over-expressed in
      a high blood pressure condition, and that this upregulated B1 R may play an
      important role in renal protection by inhibiting renal fibrosis via an increase
      of NO production and a suppression of TGFbeta1 expression and mitogen-activated
      protein kinase (ERK and p38) phosphorylation.

PMID- 15253106
TI  - Endothelin-1 gene expression in endothelial cells is potently inhibited by a
      vasodilator, dilazep.
AB  - Endothelin-1 (ET-1) is considered to be involved in various cardiovascular and
      renal disorders. The objective of this study was to investigate whether a
      vasodilator and antiplatelet agent, 1,4-bis[3-(3,4,5-trimethoxybenzoyloxy)
      propyl]perhydro-1,4-diazepine dihydrochloride monohydrate (dilazep, DZ), has an
      ET-1-inhibiting effect in vitro. Bovine aortic endothelial cells (BAEC) and human
      umbilical vein endothelial cells (HUVEC) pretreated with fetal calf serum were
      treated with DZ and preproET-1 (PpET-1) transcription was evaluated by Northern
      blot analysis. ET-1 peptide release in culture medium was evaluated by
      radioimmunoassay. The effect of DZ on the ET-1 promoter/enhancer apparatus was
      evaluated in transfection experiments using -5 kb ET-1 promoter/enhancer
      constructs. Modest inhibition of PpET-1 gene transcription was detected after 30
      min of DZ treatment (0.56+/-0.19 vs. 1 , p<0.01) and more marked inhibition was
      seen at 24 h (0.04+/-0.04 vs. 1, p<0.0001). ET-1 peptide release was suppressed
      strongly after 3 h (382.5+/-2.9 vs. 673.5+/-74.5pg/ml, p< 0.001) and 24 h (38.8+/
      9.8 vs. 5,075+/-52.0pg/ml, p<0.0001). DZ potently inhibited PpET-1 transcription
      in a concentration-dependent manner (0.42+/-0.18 vs. 1, p<0.001, at
      100micromol/l). DZ suppressed PpET-1 transcription in confluent HUVEC at 3 h
      (0.41 +/-0.11 vs. 1, p<0.0001). DZ strongly inhibited PpET-1 transcription after
      1 h of thrombin (TH) treatment (0.30+/-0.01 vs. 1.51+/-0.03, p<0.0001).
      Transfection experiments using the 5 kb ET-1 promoter-luciferase plasmid revealed
      that DZ strongly suppressed ET-1 promoter activity by 99% (p<0.01). DZ potently
      inhibited ET-1 gene expression at the transcription level in serum- or TH-treated
      endothelial cells.

PMID- 15253107
TI  - Expression of peroxisome proliferator-activated receptor isoform proteins in the
      rat kidney.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      mediating ligand-dependent transactivation. Among the 3 isoforms, PPAR- alpha is
      involved in lipid metabolism in the liver, while PPAR-gamma(-gamma1 and -gamma2)
      is involved in adipocyte differentiation. Recently, PPARs have been suggested to
      be involved in renal electrolyte metabolism as well as atherosclerosis. PPAR
      alpha is known to regulate cytochrome P450 gene expression, and may possibly
      affect sodium retention in the kidney. Moreover, PPAR-gamma is involved in the
      transcription regulation of blood pressure regulatory genes, including
      thromboxane and angiotensin II type 1 receptors. In the kidney, although
      expression of PPARs has been reported, detailed immunohistochemical analyses have
      not been performed. We here generated isoform-specific anti-PPAR antibodies to
      localize their proteins in the kidney. Anti-PPAR antibodies were raised against
      synthetic peptides. Their isoform specificity was confirmed by immunoblot
      analyses, immunoprecipitations, and antibody supershift experiments by
      electrophoretic mobility shift assay. We therefore studied the protein expression
      of PPARs in the kidney of adult Sprague-Dawley rats using these antibodies.
      Immunoblot analyses demonstrated protein expression of PPAR-alpha and -gamma1,
      but not of -gamma2, in the kidney nuclear extracts. Immunohistochemical analyses
      demonstrated that both PPAR-alpha and -gamma1 proteins were widely expressed in
      the nuclei of mesangial and epithelial cells in glomeruli, proximal and distal
      tubules, the loop of Henle, medullary collecting ducts, and intima/media of renal
      vasculatures. PPAR-alpha and -gamma1 proteins are thus widely expressed along the
      nephron segments, and may affect gene expression at these segments. Further
      studies will be needed to identify additional target genes for PPARs along the
      nephron segments.

PMID- 15253108
TI  - Effects of angiotensin II type 1 receptor antagonist on pressor responses to
      pulsatile compression of the rostral ventrolateral medulla in rats.
AB  - The rostral ventrolateral medulla (RVLM) is known to be a major center regulating
      sympathetic and cardiovascular activities. A possible association between
      neurovascular compression of the RVLM and essential hypertension has been
      indicated. The present study was performed to determine the role of angiotensin
      II (AngII) in the pressor and sympathetic responses to pulsatile compression of
      the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate
      (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM
      pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII
      type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2)
      receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to
      determine the role of glutamate and AngII in the pressor and sympathetic effects
      to the RVLM compression, kynurenate, candesartan, or PD123319 was locally
      injected before pulsatile compression of the RVLM. Finally, to determine the
      effects of peripherally administered AngII antagonists in these pressor and
      sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05
      micromol was intravenously injected before pulsatile compression of the RVLM. Glu
      injected into the RVLM significantly increased mean arterial pressure (MAP) and
      splanchnic sympathetic nerve activity (SNA), and these effects were reduced by
      RVLM pretreatment with kynurenate, but were unaffected by candesartan or
      PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also
      increased MAP and SNA. However, in contrast with Glu injections, these effects
      were reduced by RVLM pretreatment with candesartan or kynurenate, but were
      unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM
      compression were reduced by intravenous pretreatment with candesartan but not
      with PD123319. These results indicate that, upon pulsatile compression of the
      RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release
      to thereby elicit sympathetic activation and pressor effects. Candesartan may
      exert its hypotensive effect at least in part by affecting the RVLM neurons to
      reduce sympathetic outflow induced by pulsatile compression of the RVLM.

PMID- 15253109
TI  - Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and
      facilitation of monocyte recruitment through monocyte chemoattractant protein-1
      production by mesangial cells.
AB  - We previously found that human chymase selectively cleaves big endothelin-1 (ET
      1) at the Tyr31-Gly32 bond and produces 31-amino acid endothelins, ET-1 (1-31),
      without any further degradation products. In this study, we investigated the
      effect of ET-1 (1-31) on the migration of cultured rat mesangial cells (RMCs) and
      on cells of the human monocytic cell line, THP-1. In addition, we examined the
      interaction between RMCs and THP-1 cells using conditioned media from ET-1 (1-31)
      stimulated RMCs. ET-1 (1-31) caused an increase in RMC migration in a
      concentration-dependent manner, and the degree of increase was similar to those
      by ET-1 and angiotensin II (All). The ET-1 (1-31)-induced increase in RMC
      migration was inhibited by BQ123, an endothelin ETA receptor antagonist, but not
      by BQ788, an endothelin ETB receptor antagonist. ET-1 (1-31) alone did not cause
      significant migration of THP-1 cells. However, significant recruitment of THP-1
      cells was observed with conditioned media taken from ET-1 (1-31)-stimulated RMCs.
      The conditioned media-induced migration of THP-1 cells was inhibited by BQ123,
      but not by BQ788. Western blotting analysis of the lysate of RMCs revealed that
      the expression of monocyte chemoattractant protein-1 (MCP-1) protein in RMCs was
      increased by treatment with ET-1 (1-31). The addition of neutralizing antibody
      for MCP-1 to the medium inhibited the migration of THP-1 cells induced by
      conditioned media from ET-1 (1-31)-stimulated RMCs. These findings suggest that
      ET-1 (1-31) play a role in glomerulonephritis (GN) via dual effects that directly
      cause the migration of mesangial cells (MCs) and may be responsible for the
      recruitment of mononuclear cells mediated through the activation of MCs. Since
      human chymase has been reported to be involved in glomerular disease, ET-1 (1-31)
      may be among the mediators.

PMID- 15253110
TI  - Efficacy of candesartan in the treatment of migraine in hypertensive patients.
AB  - Triptans are usually administered for migraine, but cannot be given to patients
      with malfunctioning cardiac or cerebral vascular systems, which commonly
      accompany hypertension. This article focuses on 8 cases in which treatment with
      candesartan was successful in reducing both the incidence and severity of
      headache in hypertensive patients with migraine. The cases reported in this
      article showed a mean improvement in Migraine Disability Assessment score from
      29.4 to 9 points and in blood pressure from 154.9/90.4 to 129.5/81.9mmHg,
      suggesting that candesartan is an extremely attractive option for the treatment
      of migraine. Although recent studies have reported the efficacy of candesartan
      for treating migraine, there has been no description of its potential advantages
      over other prophylactic drugs. The present study included patients who could not
      tolerate triptans for whom triptans were contraindicated, several patients for
      whom other migraine prophylactic drugs showed little or no effect, and one
      patient for whom candesartan was prescribed initially for hypertension, but was
      also found to be therapeutic for migraines. Thus candesartan is considered to be
      a unique, attractive choice of prophylactic agent for migraine complicated by
      hypertension.

PMID- 15253111
TI  - Reverse iontophoresis for non-invasive transdermal monitoring.
AB  - Iontophoresis is the application of a small electric current to enhance the
      transport of both charged and polar, neutral compounds across the skin.
      Manipulation of either the total charge delivered and/or certain electrode
      formulation parameters allows control of electromigration and electroosmosis, the
      two principal mechanisms of transdermal iontophoresis. While the approach has
      been mainly used for transdermal drug delivery, 'reverse iontophoresis', by which
      substances are extracted to the skin surface, has recently been the subject of
      considerable effort. Glucose monitoring has been extensively studied and other
      applications, including therapeutic drug monitoring, are contributing to the
      development of the technique. An internal standard calibration procedure may
      ultimately render this novel monitoring technique completely non-invasive.

PMID- 15253112
TI  - Spirometry and forced oscillometry assisted optimal frequency band determination
      for the computerized analysis of tracheal lung sounds in asthma.
AB  - We analysed respiration sounds of individual asthmatic patients, in the scope of
      the development of a method for computerized recognition of the degree of airway
      obstruction. Respiration sounds were recorded during laboratory sessions of
      histamine-provoked airway obstruction. We applied an interpolation technique
      using supervised artificial neural networks to investigate the optimal frequency
      band required for studying tracheal asthmatic lung sounds. The optimal band was
      found to be 100-2300 Hz. The forced expiratory volume in 1 s (FEV1) and the
      respiratory resistance parameter Rrs(4) were used to describe the degree of
      airway obstruction that is associated with the lung sounds. By comparing the
      results obtained with the two parameters, we found that for parametrization of
      the associated degree of airway obstruction respiratory resistance measurements
      are preferable over forced expiratory volume measurements.

PMID- 15253113
TI  - Modeling of hemoglobin in dengue fever and dengue hemorrhagic fever using
      bioelectrical impedance.
AB  - This paper describes a model for predicting hemoglobin (Hb) by using
      bioelectrical impedance analysis (BIA) in dengue patients in the Hospital
      Universiti Kebangsaan Malaysia (HUKM). Bioelectrical impedance measurements were
      conducted on 83 (47 males and 36 females) serologically confirmed dengue fever
      (DF) and dengue hemorrhagic fever (DHF) patients during their hospitalization.
      The predictive equation for Hb was derived using multivariate analysis. We
      investigated all the parameters in BIA, patients' symptom and demographic data.
      In this developed model, four predictors (reactance (XC), sex, weight and
      vomiting) were found to be the best predictive factors for modeling Hb in dengue
      patients. However, the model can only explain approximately 42% of the variation
      in Hb status, thus single frequency bio-impedance stand-alone technique is
      insufficient to monitor Hb for the DF and DHF patients. Further investigation
      using multi-frequency BIA is recommended in modeling Hb to achieve the most
      parsimonious model.

PMID- 15253114
TI  - The reconstruction, from a set of points, and analysis of the interior surface of
      the heart chamber.
AB  - Adequate description of heart muscle electrical activity is essential for the
      proper treatment of cardiac arrhythmias. Contemporary mapping and ablating
      systems allow a physician to introduce an electrode (catheter) into the human
      heart, to measure the position of the electrode in space and, simultaneously, the
      electrical activity timing and the bipolar and unipolar signal amplitudes--which
      correspond to the electrical viability of the heart muscle. If enough data points
      are collected, an approximate reconstruction of the heart chamber geometry
      (anatomy) is possible using also surface data such as the viability and local
      activity isochrones. Myocardial viability in patients after myocardial infarction
      is crucial for understanding and treating life threatening arrhythmias. Although
      there are commercial tools for heart chamber reconstruction, they lack the
      ability to quantitatively analyse the reconstructed data. Here, we show a method
      of reconstruction of the left ventricle of the heart from a measured set of data
      points and perform an interpolation of the measured voltages over the
      reconstructed surface. Next, we detect regions with voltage in a specified range
      and compute their areas and circumferences. Our methods allowed us to
      quantitatively describe the 'normal' muscle, the damaged or scar areas and the
      border zones between healthy muscle and the scars. In particular, we are able to
      find geometries of the damaged muscle areas that may be dangerous, e.g. when two
      such areas lie close to each other creating an isthmus--a macroreentry arrhythmia
      substrate. This work was inspired by a clinical hypothesis that the size of the
      border zone corresponds to the rate of occurrence of ventricular arrhythmia in
      patients after myocardial infarction.

PMID- 15253115
TI  - Protocol to assess robustness of ST analysers: a case study.
AB  - This paper proposes principles and methods for assessing the robustness of ST
      segment analysers and algorithms. We describe an evaluation protocol, procedures
      and performance measures suitable for assessing the robustness. An ST analyser is
      robust if its performance is not critically dependent on the variation of the
      noise content of input signals and on the choice of the database used for
      testing, and if its analysis parameters are not critically tuned to the database
      used for testing. The protocol to assess the robustness includes: (1) a noise
      stress test addressing the aspect of variation of input signals; (2) a bootstrap
      evaluation of algorithm performance addressing the aspect of distribution of
      input signals and (3) a sensitivity analysis addressing the aspect of variation
      of analyser's architecture parameters. An ST analyser is considered to be robust
      if the performance measurements obtained during these procedures remain above the
      predefined critical performance boundaries. We illustrate the use of the
      robustness protocol and robustness measures by a case study in which we assessed
      the robustness of our Karhunen-Loeve transform based ischaemic ST episode
      detection and quantification algorithm using the European Society of Cardiology
      ST-T database.

PMID- 15253116
TI  - Resistivity probing of multi-layered tissue phantoms using microelectrodes.
AB  - We present the use of an array of rectangular microelectrodes to discriminate
      between different resistivities in a thin, layered sample. Each electrode was 8
      mm long and 200 nm thick. The electrode widths ranged from 20 to 500 microm. The
      electrodes were designed such that all pairs of consecutive electrodes had the
      same relative geometry, and therefore identical cell constants. A hydrogel-based
      tissue phantom, made by photopolymerization of 2-hydroxyethyl methacrylate
      (HEMA), was developed. By changing the hydrogel composition and the ionic
      strength of the storage medium, the resistivity of the hydrogels could be tuned
      between 100 omegam and 100 komegam. Using bipolar measurements, the tissue
      phantoms were characterized in the frequency range from 100 Hz to 30 MHz. The
      relative resistivity distribution of a three-layered structure composed of 120
      microm sheets could be calculated and was shown to agree to within 7% of the bulk
      measurements. Potential clinical applications for this technique include probing
      of epithelial tissue and skin cancer screening.

PMID- 15253117
TI  - pO2 and regional blood flow in a rabbit model of limb ischemia.
AB  - Oxygen tension (pO2) in muscles and regional blood flow were measured in a rabbit
      model of limb ischemia. pO2 was measured repetitively by EPR oximetry with EMS
      char in four different muscle groups in the same animals. Blood flow in the same
      muscles at several time points was measured using microspheres. A linear mixed
      effects model was developed to analyze the data on pO2 and blood flow. The
      results suggest that while under normal conditions pO2 in muscles does not depend
      significantly on blood flow, immediately after arterial occlusion pO2 correlates
      linearly with blood flow. Within two weeks of occlusion the pO2 is recovered to
      45% of baseline. This study demonstrates, for the first time, the applicability
      of EPR oximetry in animals larger than rodents.

PMID- 15253118
TI  - Comparison of the Bod Pod and dual energy x-ray absorptiometry in men.
AB  - The majority of studies investigating the accuracy of the Bod Pod have compared
      it to hydrostatic weighing (HW), the long held, and perhaps outdated 'gold
      standard' method of body composition analysis. Much less research has compared
      the Bod Pod to dual energy x-ray absorptiometry (DXA), a technique that is
      becoming popular as an alternative reference method. The purpose of this study
      was to compare per cent fat estimates by the Bod Pod to those of DXA in a large
      number of men. Participants were 160 men (32 +/- 11 years). Per cent body fat was
      estimated to be 19.4 +/- 6.8 and 21.6 +/- 8.4 for DXA and the Bod Pod,
      respectively. Although the two methods were highly correlated (0.94), the mean
      difference of 2.2% was significant (p < 0.01). The amount of difference increased
      as body fatness increased (p < 0.0001). The results of this study indicate that a
      difference between methods existed for our sample of men. It is uncertain exactly
      where the difference lies. Practitioners should be aware that even with the use
      of technologically sophisticated methods (i.e., Bod Pod, DXA), differences
      between methods exist and the determination of body composition is at best, an
      estimation.

PMID- 15253119
TI  - Validation of airflow perturbation device resistance measurements in excised
      sheep lungs.
AB  - The airflow perturbation device (APD) is a recently redesigned instrument to
      measure resistance in the respiratory system. The APD is small and easy to use,
      gives rapid resistance measurements, and can easily separate inhalation from
      exhalation components. It also possesses some operational characteristics similar
      to forced oscillation (FO). Excised sheep lungs within a respiratory chamber were
      used to determine the effective resistance domain of the APD. Retrograde
      catheters were installed in the airways, alveolar capsules were used to measure
      alveolar pressures, and chamber pressure was used as pleural pressure. FO
      measurements were made to compare with the APD. The APD was found to give a
      resistance measurement about 1.7 to 1.9 times airway resistance. FO gave a
      resistance measurement 1.4 times airway resistance. Resistance values differed
      depending on analysis procedure and frequency of oscillation. Both devices were
      found to produce oscillations beyond the pleural surface of the lungs. It was
      concluded that the APD and FO measure similar respiratory resistances.

PMID- 15253120
TI  - Carotid flow rates and flow division at the bifurcation in healthy volunteers.
AB  - In nine healthy subjects, magnetic resonance imaging was used to measure blood
      flow waveforms in the common (CCA), internal (ICA) and external (ECA) carotid
      arteries. Useful data were acquired from 14 carotid arteries in total. Flow rates
      were determined from regions of interest placed over the arteries in CINE-phase
      contrast velocity encoded images. Use of a normalized cardiac cycle allowed the
      combination of flow waveforms from individuals. Time-averaged group mean flow
      rates were 6.16, 4.14 and 1.59 ml s(-1) for the CCA, ICA and ECA, respectively.
      Time-averaged values for the flow division ratios ICA/CCA, ECA/ICA and ECA/CCA
      were 0.70, 0.39 and 0.26, respectively. The data will be of use in future
      physiological studies and in computational modelling of carotid artery
      haemodynamics.

PMID- 15253121
TI  - IR ear thermometers: what do they measure and how do they comply with the EU
      technical regulation?
AB  - Medical diagnostics and clinical practice rely extensively on test and
      measurement instrumentation. It is therefore of paramount importance that test
      and measurement instrumentation provides reliable data of sufficient stability,
      within appropriate limits of accuracy. At the same time the intended purpose of a
      particular measuring instrument has to be taken into account. The essential
      problem of every measuring instrument is that it measures and indicates basically
      what appears at the input of the measuring instrument, which might be
      significantly different from the real condition of a measurand. Namely, it is
      assumed that a measurand is stable, repeatable, and relatively unsusceptible to
      environmental influences. All these requirements are difficult to assure in a
      biological system and especially difficult in medical practice. Technology could
      easily provide high-resolution measurements, but due to natural instability of a
      measurand and various influential parameters the measurement uncertainty is
      inevitable. Sometimes even gross measurement errors are introduced. To achieve
      the expected accuracy for intended purpose is therefore much more demanding than
      merely relying on manufacturers' specifications. This paper describes and
      analyses the mentioned dilemmas in the case of widely used infrared ear
      thermometers, with their benefits and limitations, as well as with regard to the
      European technical regulation in the field of medical devices.

PMID- 15253122
TI  - The classification of oesophageal 24 h pH measurements using a Kohonen self
      organizing feature map.
AB  - Analysis of 24 h oesophageal pH studies can be problematic with many patients
      asymptomatic during the investigation, despite observations of reflux. The aim of
      this study was to carry out a cluster analysis of ambulatory pH studies to
      determine any underlying patterns and classes within the data. The results of 900
      24 h pH studies were investigated using the Kohonen self-organizing feature map
      (SOFM), a neural network that can be used to identify clusters within
      multidimensional data. The clinical features were presented to the network and
      the main classes identified. The SOFM-based analysis showed that patients
      clinically assessed as having symptomatic reflux during the study could be
      described by four major classifications. The results also showed that the
      probability of identifying a correlation between symptoms and reflux during an
      investigation varies from 0.49 to 0.78 for the classes identified. The developed
      network may be a useful tool in the classification of pH data. The cluster-based
      technique may offer an alternative to standard statistical techniques for high
      dimensional gastrointestinal data and form the basis of an expert system for the
      automated analysis of pH data.

PMID- 15253123
TI  - Effects of RR segment duration on HRV spectrum estimation.
AB  - Although patterns of heart rate variability (HRV) hold considerable promise for
      clarifying issues in clinical applications, the inappropriate quantification and
      interpretation of these patterns may obscure critical issues or relationships and
      may impede rather than foster the development of clinical applications. The
      duration of the RR interval series is not a matter of convenience but a fine
      balance between two important issues: acceptable variance and stationarity of the
      time series on one hand, and acceptable resolution of the spectral estimate and
      reduced spectral leakage on the other. Further, in the standard short-term HRV
      analysis, it has been observed that the previous studies in HRV spectral analysis
      use a wide range of RR interval segment duration for spectral estimation by
      Welch's algorithm. The standardization of RR interval segment duration is also
      important for comparisons among studies and is essential for within-study
      experimental contrasts. In the present study, a comparative analysis for RR
      interval segment durations has been made to propose an optimal RR interval
      segment duration. Firstly a simulated signal was analyzed with Hann window and
      zero padding for the segment lengths of 1024, 512, 256 and 128 samples resampled
      at 4 Hz with 50% overlapping. Again, the above procedure was applied to RR
      interval series and it was concluded that segment length of 256 samples with 50%
      overlapping provides a smoothed spectral estimate with clearly outlined peaks in
      low- and high-frequency bands. This easily understandable and interpretable
      spectral estimate leads to a better visual and automated analysis, which is not
      only desirable in basic physiology studies, but also a prerequisite for a
      widespread utilization of frequency domain techniques in clinical studies, where
      simplicity and effectiveness of information are of primary importance.

PMID- 15253124
TI  - Use of a priori information in estimating tissue resistivities--application to
      human data in vivo.
AB  - Accurate resistivity values are necessary to construct reliable numerical models
      to solve forward/inverse problems in EEG and to localize activity centres in
      functional brain imaging. These models require accurate geometry and resistivity
      distribution. The geometry may be extracted from high resolution images. The
      resistivity distribution may be estimated by using a statistically constrained
      minimum mean squared error estimator algorithm that has been developed previously
      by Baysal and Eyuboglu. In this study, the data are obtained by EEG and MEG
      sensors during SEF/SEP experiments that involve nine human subjects. The
      numerical model is realistic, subject-specific and the scalp, the skull and the
      brain resistivities are estimated. By performing nine different estimations, we
      found average resistivities of 3.183, 64.559 and 2.833 omega m for scalp, skull
      and brain, respectively, all under 9% standard deviation. The discrepancies
      between these results and other works are discussed in detail.

PMID- 15253125
TI  - Assessment of the hypoxic-ischemic encephalopathy in neonates using non-invasive
      near-infrared spectroscopy.
AB  - This paper introduces a method of monitoring cerebral oxygenation for healthy
      neonates and neonates with hypoxic-ischemic encephalopathy (HIE) using near
      infrared spectroscopy. The object of this study was to investigate whether or not
      there were differences between the HIE group and the healthy group in terms of
      NIRS parameters. The subjects were all term neonates, their age ranging from 2 to
      18 days. The healthy group included 25 subjects while the HIE group consisted of
      16 patients. A prototype NIRS instrument, which provides the data of tissue
      oxygenation including regional oxygen saturation (rSO2), the increment of
      oxyhemoglobin concentration and hemoglobin (deltaHbO2 and deltaHb) was used, and
      the data of rSO2 was compared with the data from the blood gas analyzer. The
      result shows that: (1) the mean+/-SD of rSO2 for the healthy group was 62 +/- 4%
      in the frontal region under the quiet sleep condition, but the mean+/-SD of rSO2
      for the HIE group was 53 +/- 3%. (2) As all subjects inhaled pure oxygen in 21
      min(-1) for a period of 60 s, rSO2 for the healthy group increased rapidly, with
      the increase in rSO2 (deltarSO2) being 7 +/- 2.3%, but the increase in rSO2 for
      the HIE neonates was 3 +/- 1.5%. After inhaling oxygen, deltaHbO2 and deltaHb
      between the two groups were also significantly different. (3) During all the
      experiments SpO2 was monitored, the value of SpO2 was not significantly different
      between the two groups. The above observations suggest that the rSO2 in quiet
      condition and the values of change of rSO2, HbO2 and Hb during the inhalation of
      oxygen may be used as the parameters to discover and assess the HIE infants.

PMID- 15253126
TI  - Detrended fluctuation analysis: a suitable method for studying fetal heart rate
      variability?
AB  - We evaluate the suitability of an enhanced detrended fluctuation analysis for
      studying fetal heart rate series involving imperfect quality of information. Our
      results indicate that to explore persistent long-range correlations, or
      fractality, the collection requirements of the data can be relaxed by allowing
      the possibility of using averaged fetal heart rate series. In addition, it also
      appears feasible to employ, without producing major alterations in the long-range
      scaling behaviour, fragmented fetal heart rate series involving up to 50% of
      random missing values, or up to 50 min of consecutive missing samples in
      recordings of approximately equal to 8 h length. These are crucial advantages to
      overcome the often variable quality of fetal data. Consequently, these findings
      may open the possibility of obtaining information concerning the development of
      neural processes from fetal heart rate series, despite their non-stationary and
      fragmented nature.

PMID- 15253127
TI  - Towards magnetic detection electrical impedance tomography: data acquisition and
      image reconstruction of current density in phantoms and in vivo.
AB  - The objective of magnetic detection electrical impedance tomography (MD-EIT) is
      to reconstruct in vivo images of conductivity from magnetic field measurements
      taken around the body. MD-EIT is performed by applying an alternating current, at
      one of a range of frequencies, to a conducting object through a pair of
      electrodes fixed to the surface of the object. Magnetic field measurements
      recorded by search coils at a number of positions around the object are used to
      determine the current distribution that is generating the magnetic field. From
      this distribution, a conductivity map of a cross-section of the object can be
      reconstructed. This paper describes the development of an MD-EIT data acquisition
      system and discusses the related image reconstruction issues. The ill-conditioned
      nature of the inverse problem is examined and a number of image reconstruction
      methods are compared. The technical feasibility of MD-EIT data collection and
      image reconstruction is demonstrated with example images of current density from
      both phantom and human data.

PMID- 15253128
TI  - Molecular anatomy of interendothelial junctions in human blood-brain barrier
      microvessels.
AB  - Immunogold cytochemical procedure was used to study the localization at the
      ultrastructural level of interendothelial junction-associated protein molecules
      in the human brain blood microvessels, representing the anatomic site of the
      blood-brain barrier (BBB). Ultrathin sections of Lowicryl K4M-embedded biopsy
      specimens of human cerebral cortex obtained during surgical procedures were
      exposed to specific antibodies, followed by colloidal gold-labeled secondary
      antibodies. All tight junction-specific integral membrane (transmembrane)
      proteins--occludin, junctional adhesion molecule (JAM-1), and claudin-5--as well
      as peripheral zonula occludens protein (ZO-1) were highly expressed.
      Immunoreactivity of the adherens junction-specific transmembrane protein VE
      cadherin was of almost similar intensity. Immunolabeling of the adherens junction
      associated peripheral proteins--alpha-catenin, beta-catenin, and p120 catenin-
      although positive, was evidently less intense. The expression of gamma-catenin
      (plakoglobin) was considered questionable because solitary immunosignals (gold
      particles) appeared in only a few microvascular profiles. Double labeling of some
      sections made possible to observe strict colocalization of the junctional
      molecules, such as occludin and ZO-1 or JAM-1 and VE-cadherin, in the
      interendothelial junctions. We found that in human brain microvessels, the
      interendothelial junctional complexes contain molecular components specific for
      both tight and adherens junctions. It is assumed that the data obtained can help
      us find the immunodetectable junctional molecules that can serve as sensitive
      markers of normal or abnormal function of the BBB.

PMID- 15253129
TI  - Dendritic spinules in rat nigral neurons revealed by acetylcholinesterase
      immunocytochemistry and serial sections of the dendritic spine heads.
AB  - Dendritic spinules of rat nigral neurons were visualized at electron microscopic
      level by acetylcholinesterase immunocytochemistry and serial sections of the
      nigral dendrites. The spinules (at least 150 nm in length and 10-20 nm in width)
      which protruded from the spine heads are found in extracellular space in the
      neuropil and particularly between nerve terminals of the presynaptic neurons and
      fine glial processes. The nigral spinules are, however, not observed as
      invaginated processes in the nerve terminals. The dendritic spinule may be
      endowed with synaptic plasticity and metabolic exchange between nerve terminals
      and glial processes.

PMID- 15253130
TI  - The relationships between neurons containing dopamine and nitric oxide synthase
      in the ventral tegmental area.
AB  - Ventral tegmental area (VTA) is a heterogeneous group of dopaminergic cells which
      contains interfascicular (IF), parabrachial (PBP) and rostral linear (RLi)
      nuclei. Neurons of this area are involved in the regulation of motor and
      motivational aspects of behavior and reveal high neuronal plasticity. Among many
      various neurotransmitters and neuromodulators, nitric oxide (NO) is localized in
      this region. In the present study, we investigated morphology and distribution of
      nitric oxide synthase (NOS)-positive neurons in VTA and their colocalization with
      dopaminergic neurons. The study was performed on six adult Wistar rats. After
      perfusional fixation, the brains were cut, immunostained for tyrosine hydroxylase
      (TH) and NOS and studied by confocal laser microscopy. In each of the three
      studied nuclei of VTA we investigated three different neuronal populations.
      Numerous TH-immunoreactive (TH-ir) and NOS-immunoreactive (NOS-ir) neurons are
      present in the studied region. Among them, a considerable number showed
      coexistence of both neurotransmitters. The populations of TH-ir and NOS-ir
      neurons interact with each other as manifested by the presence of NOS-ir endings
      on TH-ir neurons and vice versa. Taking the above into account, it may be
      suspected that NO is involved in the modulation of dopaminergic transmission.

PMID- 15253131
TI  - Adrenergic, nitrergic and peptidergic innervation of the urethral muscle in the
      boar.
AB  - In this study, the innervation of the urethral muscle in adult male pigs was
      investigated using combined NADPH-diaphorase (NADPH-d) histochemistry and
      immunocytochemistry. Nerve fibres supplying the urethral muscle were found to
      show NADPH-d activity and they also expressed immunoreactivity to catecholamine
      synthesising enzymes including tyrosine hydoxylase (TH) and dopamine-beta
      hydroxylase (DbetaH) as well as to: vasoactive intestinal polypeptide (VIP) and
      neuropeptide Y (NPY). Different subpopulations of the nerve fibres (NADPH-d
      positive, TH-, DbetaH-, VIP- and NPY-immunoreactive (IR), but also NADPH-d/VIP-
      and NADPH-d/NPY-IR) were disclosed. These nerve fibres were observed not only to
      run among muscle fibres of the urethral muscle, but also within extrinsic nerve
      trunks. Moreover, in the organ studied, numerous ganglia were found. The
      intramural ganglia, composed of a few to 30 neurons were located in the proximal,
      middle and distal regions of the pelvic urethra. In the vicinity of the urethral
      muscle, there were mainly small ganglia containing two to several neurons, but
      also larger ganglia consisting of up to tens neurons were encountered in the
      connective tissue surrounding the pelvic urethra. In the ganglia observed in the
      neighbourhood of the urethral muscle, different subpopulations of nerve cells
      were found, namely: catecholaminergic, nitrergic, VIP-IR, NPY-IR and also NADPH
      d/DbetaH-, NADPH-d/VIP- and NADPH-d/NPY-positive. Possible sources of the
      innervation for this muscle were also discussed.

PMID- 15253132
TI  - Segmental distribution and morphometric features of primary sensory neurons
      projecting to the tibial periosteum in the rat.
AB  - Previous reports have demonstrated very rich innervation pattern in the
      periosteum. Most of the periosteal fibers were found to be sensory in nature. The
      aim of this study was to identify the primary sensory neurons that innervate the
      tibial periosteum in the adult rat and to describe the morphometric features of
      their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was
      injected into the periosteum on the medial surface of the tibia. The perikarya of
      the sensory fibers were traced back in the dorsal root ganglia (DRG) L1-L6 by
      means of fluorescent microscopy on cryosections. DiI-containing neurons were
      counted in each section and their segmental distribution was determined. Using PC
      assisted image analysis system, the size and shape of the traced perikarya were
      analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia
      were located in the DRG ipsilateral to the injection site, with the highest
      distribution in L3 and L4 (57% and 23%, respectively). The majority of the traced
      neurons were of small size (area < 850 microm2), which is consistent with the
      size distribution of CGRP- and SP-containing cells, regarded as primary sensory
      neurons responsible for perception of pain and temperature. A small proportion of
      labeled cells had large perikarya and probably supplied corpuscular sense
      receptors observed in the periosteum. No differences were found in the shape
      distribution of neurons belonging to different size classes.

PMID- 15253133
TI  - In vivo accumulation of self-assembling dye Congo red in an area marked by
      specific immune complexes: possible relevance to chemotherapy.
AB  - Supramolecular micellar structures have been proposed as carriers in aim-oriented
      drug transportation to a target marked by specific immune complexes. In this
      study, the self-assembling dye Congo red was used as a model supramolecular
      carrier and its accumulation in the target was studied in vivo. The target was
      created in vivo as the local specific inflammation provoked by subcutaneous
      injection of antigen to the ear of a previously immunized rabbit. The color
      caused by accumulation of Congo red after its intravenous injection was
      registered by pictures of the ear with suitably filtered visible light shining
      through it to distinguish Congo red against the background color of hemoglobin.
      The results confirmed the expected accumulation and retention of Congo red in the
      inflammation area marked by deposits of specific immune complexes. The role of
      albumin and its possible interference with transportation of drugs through the
      blood by supramolecular carriers was also subjected to preliminary examination.
      The results revealed that albumin collaborates rather than interferes with drug
      transportation; this is another factor making the use of supramolecular carriers
      for aim-oriented chemotherapy highly promising.

PMID- 15253134
TI  - Prognostic significance of epidermal growth factor receptor in surgically treated
      squamous cell lung cancer patients.
AB  - Epidermal growth factor receptor (EGFR) is one of signalling pathways activated
      during premalignant proliferative changes in the airway epithelium. However there
      is no agreement about prognostic significance of EGFR expression in non-small
      cell lung cancer (NSCLC). Facts mentioned above prompted us to study EGFR
      expression in the group of 78 surgically treated squamous cell lung cancer
      (SqCLC) patients. The EGFR expression was visualized in formalin-fixed, paraffin
      embedded sections, using immunohistochemistry. Three methods of assessment of
      EGFR expression were applied: percentage of cells with membranous EGFR expression
      -EGFR labellig index (EGFR LI), percentage of fields with membranous EGFR
      staining (PS%) and staining intensity (absent, weak or strong) in the whole
      specimen (SI). Mean EGFR LI and PS% values were 30.4 +/- 3.5% and 51.6 +/- 3.9%,
      respectively. Patients with higher EGFR expression (EGFR LI, PS%, SI) were
      significantly younger than those with low EGFR expression. EGFR LI was higher in
      pT3 tumours than in pT1+pT2 tumours, moreover, EGFR expression (EGFR LI, PS%, SI)
      was significantly higher in G1+G2 tumours than in G3 tumours. There were
      significant correlations between parameters used for assessment of EGFR
      expression. PS% < or = 50 indicated shorter disease-specific survival than PS% >
      50. However, patients with tumours with both very low and very high EGFR LI (13%
      > or = EGFR LI > 80%) showed significantly shorter survival than those with
      medium EGFR LI (13% < GFR LI < or = 80%). Additionally, pTNM and pN significantly
      influenced patients' survival. In multivariate analysis, EGFR LI and pTNM were
      independent prognostic parameters influencing disease-specific survival of
      patients.

PMID- 15253135
TI  - Distribution of the DAZ gene transcripts in human testis.
AB  - Involvement of variety of genes, especially located on Y chromosome, is critical
      for the regulation of spermatogenesis. In particular, fertility candidate genes
      such as deleted in azoospermia (DAZ) are believed to have important function in
      sperm production, since DAZ is frequently deleted in azoospermic and severy
      oligozoospermic men. The role of the DAZ gene is supported by its exclusive
      expression in the testis and by its deletion in about 10% of azoospermic and
      severely oligozoospermic patients. The distribution of DAZ transcripts in
      seminiferous epithelium of human testis is reported in the present study. The use
      of Adobe Photoshop and Scion Image softwares allowed for semi-quantitative
      analysis of in situ RT-PCR (ISRT-PCR) results. The intensity of ISRT-PCR
      product's fluorescence was different within individual seminiferous tubules. It
      was clearly shown by using the pseudocolour scale and transforming the intensity
      of the fluorescence into levels of greyscale images. The more intense
      fluorescence characterised single spermatogonia and those organized in small
      groups inside separate tubules. The most intense accumulation of DAZ mRNA was
      observed in spermatogonia.

PMID- 15253136
TI  - Localization of human chorionic gonadotropin beta subunit transcripts in ovarian
      cancer tissue.
AB  - Recent studies demonstrated that besides placenta and malignant trophoblastic
      tumors, hCG and especially its beta-subunit is secreted by a varieties of tumors
      of different origin. The aim of the present investigation was to determine the
      expression pattern of human chorionic gonadotropin gene in ovarian cancer tissue.
      The study included 8 patients with epithelial ovarian carcinoma. The expression
      and distribution of hCGbeta mRNA was assessed by in situ RT-PCR method. The semi
      quantitative assessment was performed using computer image analysis.
      Transformation of the images into the pseudocolour scale showed a clear
      difference in fluorescence intensity among individual cancer cells. The intensity
      of ISRT-PCR products corresponding with expression level of hCGbeta demonstrated
      that its production by individual cancer cells is different. In all studied
      specimens of the ovarian carcinoma tissue, cancer cells characterized by the
      presence of active hCGbeta gene were found, whereas noncancerous tissue
      demonstrated lack of the gene expression. Thus, the study clearly shows that the
      expression of hCGbeta is the feature of ovarian cancer tissue.

PMID- 15253137
TI  - The effect of new anthracycline derivatives on the induction of apoptotic
      processes in human neoplastic cells.
AB  - This study was an attempt to determine the effect of a selected anthracycline
      derivative, WP903, on apoptotic processes in human melanoma cells depending on
      intracellular concentrations of the compound, and to evaluate the significance of
      apoptosis induction for the cytotoxic effect of anthracycline antibiotics. It was
      found that the WP903, contrary to ADR (adriamycin) is a strong inducer of
      apoptotic processes in ME18 human melanoma cells regardless of their
      susceptibility to adriamycin and WP903. The cells were treated for 24 h with ADR
      (1 and 5 microg/ml) or WP903 (0.2 and 2 microg/ml). Apoptosis was detected with
      the use of annexin V-FITC and PI (propidium iodide) and with TUNEL assay. WP903
      used at 0.2 microg/ml induced early apoptosis in 23% of ME18 cells and in 60% of
      ME18/R cells; at 2 microg/ml in 70% of each of cell line tested. Significant late
      apoptotic effect was observed in ME18 cells. In contrast, ADR was found to be a
      weak inducer of apoptotic events. The results suggest that apoptosis is not a
      mechanism directly related to the cytotoxic effect of anthracycline antibiotics.

PMID- 15253138
TI  - Effect of 5-aminolevulinic acid on kinetics of protoporphyrin IX production in
      CHO cells.
AB  - 5-aminolevulinic acid (ALA) is utilized in a photodynamic therapy as a compound
      capable of augmenting intracellular pool of protoporphyrin IX (PpIX), which
      exhibits properties of a photosensitizer. The studies were aimed at monitoring
      accumulation of endogenous protoporphyrin IX in CHO cells under effect of various
      concentrations of ALA in culture medium and following removal of the compound
      from the culture medium. Cell content of PpIX was determined following incubation
      of the cells for 72 h in a culture medium containing different concentration of
      ALA. Moreover, the cells were preincubated for 2 h in ALA at various
      concentrations and separated from the compound by medium change and their PpIX
      content was monitored following incubation. PpIX content was defined by a
      fluorescent technique under the confocal microscope. In the course of continuous
      incubation of cells with ALA, biphasic alterations were noted in cellular PpIX
      concentration. Removal of ALA from the incubation medium resulted at first in a
      decrease in PpIX content in cells, which was followed by an evidently augmented
      accumulation of the compound in the cells. The results suggested that in the case
      of CHO cells, exogenous ALA was not an exclusive source of PpIX synthesis and
      that alterations in enzyme activities were responsible for production of PpIX.

PMID- 15253139
TI  - [Therapeutic angiogenesis of critical lower limb ischemia. Review of the
      literature and prospects of research on stem cells].
AB  - Chronic peripheral arterial disease affects up to 15% of adults over the age of
      55 years; critical limb ischemia represents the most dramatic clinical outcome.
      Patients with chronic critical limb ischemia who are not candidate for surgical
      or percutaneous revascularization have impending limb loss; those who benefit
      from successful revascularization suffer from high rate of recurrent symptoms or
      revision surgery or progressive amputations. In these patients no medical
      treatment is considered effective for rest pain or ulcer healing. Therapeutic
      angiogenesis, which has the goal to achieve the process of new blood vessel
      formation via the administration of growth factors, has become a new promising
      hope. The discovery of the possibility of inducing sprouting of new vessels from
      preexisting vasa (angiogenesis) or the in situ differentiation of endothelial
      cells from stem cell precursors (vasculogenesis) have open new lease on life.
      However, a careful analysis of experimental results achieved in animal models is
      required before proposing for clinical setting. Although a major concern is that
      most of the experimental work has been done on animal models that do not
      represent the clinical process, benefit from growth factor administration or stem
      cell therapy has been proven in clinical trials, suggesting the importance of
      this new research frontier. This literature review is aimed to examine potential
      applications of therapeutic angiogenesis to treat critical limb ischemia with
      particular attention to angiogenesis obtained with stem cells.

PMID- 15253140
TI  - [Family screening of patients with premature coronary artery disease:
      opportunities and challenges of cardiovascular health in the 21st century].
AB  - A positive family history of premature coronary heart disease is a strong and
      independent risk factor for relatives and its effect is synergistic with other
      traditional and not traditional risk factors. It is well documented a familial
      aggregation of premature coronary heart disease particularly related to family
      clustering of several cardiovascular risk factors. The screening and the
      identification, by a comprehensive cardiovascular risk factor assessment, of high
      risk relatives of patients with premature coronary artery disease by
      cardiologists and general practitioners is crucial. A family-centered approach to
      the prevention of coronary artery disease represents an opportunity and a
      challenge for promoting cardiovascular health in the 21st century.

PMID- 15253141
TI  - [Stem cell mobilization after coronary artery bypass grafting].
AB  - BACKGROUND: Recently, the role of stem cells as a potential therapeutic tool for
      ischemic heart disease has been evaluated by a number of experimental and
      clinical studies. Although preliminary clinical data appear to be promising, the
      precise pathophysiological role of stem cell mobilization during acute myocardial
      ischemia remains uncertain. The present study was aimed at assessing factors
      affecting stem cell mobilization after coronary artery bypass grafting used as a
      clinical model of controlled myocardial ischemia. METHODS: Eighteen patients (16
      men, 2 women, mean age 66 +/- 8 years) with three-vessel coronary artery disease
      undergoing coronary artery bypass grafting were included in the study; 24 age-
      and sex-matched healthy subjects served as controls. On admission, 10 patients
      had stable angina and 8 had unstable angina. Clinical history and instrumental
      evidence of previous myocardial infarction were present in 11 patients. Venous
      peripheral blood was sampled at baseline and 6, 24, 48 and 72 hours after
      coronary surgery. Duration of cardiac arrest and extracorporeal circulation were
      recorded as well as the release of total creatine kinase (CK), CK-MB, troponin I
      and C-reactive protein. CD34+ stem cells were analyzed by flow cytometry
      according to published methods. RESULTS: In patients with ischemic heart disease
      the peripheral concentration of CD34+ cells was higher than that of control
      subjects (0.202 +/- 0.30 vs 0.068 +/- 0.059%, p = 0.03). However, patients with
      stable and unstable angina had similar concentration of CD34+ cells (0.171 +/-
      0.33 vs 0.241 +/- 0.275%, p = 0.63) as well as patients with and without previous
      myocardial infarction (0.134 +/- 0.19 vs 0.245 +/- 0.352%, p = 0.4). Coronary
      artery bypass grafting caused a non-significant increase in concentration of
      CD34+ cells at 24 hours which was similar in patients with stable and unstable
      angina. Finally, no significant correlation was found between peripheral
      concentration of CD34+ cells and aortic clamping and extracorporeal circulation
      duration, peak release of total CK, CK-MB, troponin I and C-reactive protein.
      CONCLUSIONS: Peripheral concentration of CD34+ stem cells is higher in patients
      with ischemic heart disease than in healthy controls but it is similar in
      patients with stable and unstable coronary syndromes. Peripheral mobilization of
      CD34+ cells is not correlated with the duration and severity of ischemic insult
      induced by surgical cardiac arrest. These preliminary findings suggest that CD34+
      cell mobilization may be modulated more by tonically active than phasic factors.

PMID- 15253142
TI  - [Biohumoral markers and right ventricular dysfunction in acute pulmonary
      embolism: the answer to thrombolytic therapy].
AB  - BACKGROUND: Recent data suggest that brain natriuretic peptide (BNP) and troponin
      I (TnII) are useful markers of right ventricular dysfunction (RVD) and initial
      myocardial injury in acute pulmonary embolism. The aim of this study was to
      evaluate biohumoral activation and right ventricular function in patients with
      acute pulmonary embolism diagnosed at pulmonary scintigraphy. METHODS: We
      observed 12 patients with massive pulmonary embolism (MPE), 8 with non-massive
      pulmonary embolism (NMPE) and RVD, 6 with NMPE without RVD. All the patients with
      MPE and 5 patients with NMPE-RVD received thrombolytic therapy (urokinase or
      recombinant tissue-type plasminogen activator), the others were treated with
      heparin. At the beginning and after pharmacological treatment all the 26 patients
      underwent standard echocardiography and blood test analysis. RESULTS: BNP and Tn1
      were significantly high in MPE (BNP p < 0.001 and Tn1I p < 0.005 vs NMPE) and in
      NMPE-RVD (BNP p < 0.03 and Tnl p < 0.02 vs NMPE). MPE and NMPE-RVD had similar
      RVD (p = NS), thrombolysis significantly reduced BNP, TnI, systolic pulmonary
      pressure, both in MPE (p < 0.001) and in NMNPE-RVD (BNP and Tnl p < 0.05,
      systolic pulmonary pressure p < 0.001). COULSION: Our data sustain the utility of
      BNP and Tnl as markers of RVD in acute pulmonary embolism; they focus on patients
      with NMPE-RVD and high levels of BNP and Tnl in whom an aggressive therapy as the
      thrombolytic one is necessary; they suggest the importance of biohumoral markers
      as indicators of the efficacy of pharmacological treatment in patients with acute
      pulmonary embolism.

PMID- 15253143
TI  - [Transthoracic cardioversion in patients with atrial fibrillation: comparison of
      three different waveforms].
AB  - BACKGROUND: Transthoracic electrical cardioversion represents the most effective
      therapy in converting atrial fibrillation (AF) to sinus rhythm. External
      cardioverter-defibrillators discharge a current with monophasic and most recently
      biphasic waveforms. Lately, many articles support the superiority of the biphasic
      waveform over the monophasic one. Moreover, we have the opportunity to use
      different biphasic waveforms. The aim of this study was to compare the efficacy
      (success rate and energy delivered) of a monophasic wave and two different
      biphasic waves, in patients with persistent AF undergoing external electrical
      cardioversion. The monophasic wave was delivered by a Zoll M series NM PDMA-9,
      while the so-called "rectilinear" biphasic waveform was used by a Zoll M series
      PDM-7S and the biphasic truncated exponential wave by a Laerdal Heartstart 4000.
      METHODS: Sixty-four patients with clinical indications to undergo external
      electrical cardioversion were randomized into three groups. All the groups were
      homogeneous for almost all characteristics, particularly atrial dimensions, body
      surface area, and duration of AF and therapy. Eighteen patients underwent
      external cardioversion with monophasic waveform (group 1), 22 patients were
      treated with rectilinear biphasic waveform (group II), and 24 patients with
      biphasic truncated waveform (group III). A cardioversion protocol, providing up
      to 5 shocks, with incremental energy levels was used. A blood sample was obtained
      6 hours later to evaluate myocardial damage due to shock therapy for each
      patient. RESULTS: Both biphasic devices demonstrated to be more effective than
      the monophasic one (group I 78%, group II 95%, group III 100%). Moreover, none of
      them caused any significant myocardial damage, evaluated in terms of cardiac
      enzyme release. Nonetheless, the biphasic truncated exponential wave demonstrated
      an efficiency of 10 0% compared to 95 % of the rectilinear one and 78% of the
      monophasic one, using less energy/patient (873 +/- 101 J group I, 390 +/- 48 J
      group II, and 280 +/- 42 J group III), at almost the same shock attempts.
      CONCLUSIONS: Biphasic truncated exponential wave seems to be more effective at a
      lower energy level.

PMID- 15253144
TI  - [Medicine and literature: a frequent elective affinity].

PMID- 15253145
TI  - [Syncope and bundle branch block: an unsolved problem].

PMID- 15253146
TI  - [Left internal mammary artery graft stenosis. Atherosclerosis, spasm or
      kinking?].
AB  - The internal mammary artery is the most frequently used bypass conduit for the
      left anterior descending coronary artery in patients treated with bypass surgery,
      with excellent long-term patency rates. However, the mammary artery may also be
      affected by functionally significant stenoses. Most stenoses of the mammary
      artery are secondary to the surgical procedure at the anastomosis site, but
      atherosclerotic lesions may also develop. The mammary artery is often tortuous
      and extreme kinking of the vessel may cause flow obstruction. The treatment of
      such kind of stenoses is not codified. The clinical course and interventional
      procedure of 2 patients with previous mammary artery bypass graft and severe
      angina due to kinking stenosis of the graft are described. The 2 cases are
      characterized by the short time frame during which the stenosis became apparent,
      suggesting a vasoactive component in the first case that was resolved with
      medical treatment and an aggressive atherosclerotic progression in the second
      that required a percutaneous intervention. Therefore, etiology of the stenosis of
      the body of the mammary artery graft may differ from that of the native
      circulation. The role of marked bends in bypass grafts could deserve selective
      studies to determine whether they are associated with the development of
      functional stenosis. This information may be useful when performing mammary
      artery bypass graft surgery for avoiding extremely twisted vessel courses.

PMID- 15253147
TI  - [Left main coronary artery aneurysm detected by myocardial scintigraphy, coronary
      angiography and multislice computed tomography].
AB  - Aneurysm of the left main coronary artery is rare and is found in 0.1% of
      angiograms. A case of left main coronary aneurysm with no flow-limiting
      atherosclerotic coronary disease in a 53-year-old male is reported. In the
      history only a familial hypercholesterolemia was present. After some episodes of
      angina at rest and positive troponin, exercise myocardial scintigraphy detected a
      septal and inferior defect only after stress. Coronary angiography reveals an
      aneurysmal dilation of the left trunk involving the origin of the left anterior
      descending and left circumflex coronary arteries, also detected at multislice
      computed tomography. No intracranial or abdominal aneurysm was associated. The
      patient was treated medically with anticoagulant medication, low doses of beta
      blockers and statins, with no adverse events at 2 and 4 months of follow-up.

PMID- 15253148
TI  - [Italian Consensus Conference on drug-eluting stents].

PMID- 15253149
TI  - Dissecting and exploiting nonribosomal peptide synthetases.
AB  - A large number of therapeutically useful cyclic and linear peptides of bacteria
      or fungal origin are synthesized via a template-directed, nucleic-acid
      independent nonribosomal mechanism. This process is carried out by mega-enzymes
      called nonribosomal peptide synthetases (NRPSs). NRPSs contain repeated
      coordinated groups of active sites called modules, and each module is composed of
      several domains with different catalytic activities. The familiarity to these
      domains lays base for the future genetic engineering of NRPSs to generate
      entirely "unnature" products. The details about NRPSs domain structures and the
      exploitation of NRPSs are described in this review.

PMID- 15253150
TI  - Predicting polymerase II core promoters by cooperating transcription factor
      binding sites in eukaryotic genes.
AB  - Several discriminate functions for predicting core promoters that based on the
      potential cooperation between transcription factor binding sites (TFBSs) are
      discussed. It is demonstrated that the promoter predicting accuracy is improved
      when the cooperation among TFBSs is taken into consideration. The core promoter
      region of a newly discovered gene CKLFSF1 is predicted to locate more than 1.5 kb
      far away from the 5' end of the transcript and in the last intron of its upstream
      gene, which is experimentally confirmed later. The core promoters of 3402 human
      RefSeq sequences, obtained by extending the mRNAs in human genome sequences, are
      predicted by our algorithm, and there are about 60% of the predicted core
      promoters locating within the +/- 500 bp region relative to the annotated
      transcription start site.

PMID- 15253151
TI  - A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG
      as a main start codon for translation initiation of human ACAT1 mRNA.
AB  - Human ACAT 1 cDNA K1 was first cloned and functionally expressed in 1993. There
      are two adjacent in-frame AUG codons, AUG(1397-1399) and AUG(1415-1417), at 5'
      terminus of the open reading frame (ORF, nt 1397-3049) of human ACAT1 mRNA
      corresponding to cDNA K1. In current work, these two adjacent inframe AUGs at 5'
      terminus of the predicted ORF (5'-ORF-AUGs) as start codons for translation
      initiation of human ACAT1 mRNA were characterized in detail. Codon mutations
      indicated that both of these two adjacent 5'-ORF-AUGs can be selected as start
      codons but the first 5'-ORF-AUG(1397-1399) is a main start codon consistent with
      that of the predicted ORF of human ACAT1 mRNA. Further deletion and mutation
      analyses demonstrated that a stable upstream stem-loop structure enhanced the
      selection of the first 5'-ORF-AUG(1397 -1399) as a main start codon, in addition
      to upstream nucleotide A in the -3 position, which is a key site of Kozak
      sequence. In addition, result of ACAT1 enzymatic activity assay showed no obvious
      difference between these two ACAT1 proteins respectively initiated from the two
      adjacent 5'-ORF-AUGs. This work showed that a stable upstream stem-loop structure
      could modulate the start codon selection during translation initiation of mRNAs
      that contain adjacent multi-5'-ORF-AUGs.

PMID- 15253152
TI  - Protection of mice with a divalent tuberculosis DNA vaccine encoding antigens
      Ag85B and MPT64.
AB  - DNA vaccine may be a promising tool for controlling tuberculosis development.
      However, vaccines encoding single antigens of mycobacterium did not produce
      protective effect as BCG did. In the present study, we evaluated the
      immunogenicity and protective efficacy of a divalent DNA vaccine encoding two
      immunodominant antigens Ag85B and MPT64 of Mycobacterium tuberculosis. We found
      that both humoral and Th1-type (high IFN-gamma, low IL-4) cellular responses
      obtained from the divalent DNA vaccine group were significantly higher than that
      conferred by BCG. RT-PCR results showed that antigens were expressed
      differentially in various organs in divalent DNA vaccine group. The survival rate
      for mice treated with the divalent DNA vaccine after challenging with high doses
      of virulent M. tuberculosis H37Rv was significantly higher than that of the BCG
      group or any of the single DNA vaccine group. Significant differences were also
      found between the single and divalent DNA vaccinated mice in terms of body,
      spleen and lung weight. Bacterial loading decreased about 2000-fold in lungs and
      about 100-fold in spleens of divalent DNA vaccinated mice when compared with that
      of the control group. We conclude that our divalent DNA vaccine may be a better
      choice for controlling tuberculosis disease in animals.

PMID- 15253153
TI  - Effects of citral on Aspergillus flavus spores by quasi-elastic light scattering
      and multiplex microanalysis techniques.
AB  - Citral refined from Litsea cubeba oil has been found to have a strong influence
      on fungi, especially Aspergillus flavus. Multiplex microanalysis and quasi
      elastic light scattering techniques were applied to study the effects of citral
      on Aspergillus flavus spores from the levels of membrane, organelle and
      intracellular macromolecule. It was found that citral injured the wall and the
      membrane of A. flavus spore, resulting in decrease of its elasticity. After
      entering the cell, citral not only influenced the genetic expression of
      mitochondrion reduplication and its morphology, but also changed the aggregation
      of protein-like macromolecules. As a result, cells, organelles and macromolecules
      lost their normal structures and functions, eventually leading to the loss of
      germination ability of A. flavus spores. Since Litsea cubeba oil as food additive
      and antifungal agent is safe and less poisonous, it is important to elucidate the
      inhibitory mechanisms of Litsea cubeba oil on the germination ability of A.
      flavus spore.

PMID- 15253154
TI  - Cloning and identification of two novel splice variants of human PD-L2.
AB  - PD-L2, a newly identified member of B7 family, plays a role in down-regulating T
      cell responses. The common PD-L2 mRNA (type I) is the splicing product containing
      all 6 exons. We report here the identification of two human PD-L2 splice variants
      in activated leukocytes. One splice variant (type II) is generated through
      splicing out exon 3 encoding Ig constant-like domain; it retains all other
      regions without a frame shift. The other variant (type III) is created by
      splicing out exon 3 to an alternative acceptor site 5 bp downstream of the
      canonical acceptor site, leading to a frame shift. Consequently, the translated
      protein should be a soluble form. Furthermore, type I isoform is expressed on the
      plasma surface whereas type II isoform showed a pattern of intracellular membrane
      distribution in the transiently transfected K562 cells. In addition, the
      expression patterns of PD-L2 splice variants are variable in different
      individuals and distinct cellular status. These results suggest that PD-L2
      expression may be controlled by posttranscriptional regulation through
      alternative splicing, and modulation of PD-L2 isoform expression may influence
      the outcome of immune response.

PMID- 15253155
TI  - The recognition of glycolate oxidase apoprotein with flavin analogs in higher
      plants.
AB  - The dependence of glycolate oxidase apoprotein (apoGO) activity on flavin analogs
      was surveyed in 9 higher plants from 7 families. Activities of all apoGOs
      depended not only on flavin mononucleotide (FMN) but also on flavin adenine
      dinucleotide (FAD), but not on riboflavin. The kinetic analysis showed that FMN
      was the optimum cofactor for apoGO from leaves of Brassica campestris. In plant
      kingdom, FMN, FAD and riboflavin are three flavin analogs with very similar
      structure, and they could coexist and be inter-converted from each other, so the
      question is how the apoprotein of glycolate oxidase (GO) recognized these flavin
      analogs. No inhibition effect of riboflavin on the activity of apoGO with FMN or
      FAD was found and no obvious quenching of riboflavin or apoGO protein
      fluorescence was detected with the addition of apoGO or riboflavin, respectively.
      These results indicated that riboflavin did not bind to apoGO tightly like FMN
      and FAD. Inorganic phosphate (Pi) did inhibit the activity of GO, and kinetic
      analysis revealed that this inhibition was caused by the competitive binding to
      apoGO between Pi and FMN. This competitive binding was further confirmed by the
      inhibition of Pi to the quenching of FMN and apoGO protein fluorescence with
      apoGO and FMN, respectively. It was suggested that the 5'-phosphate group of FMN
      or FAD may play a key role in the recognition and binding of riboflavin analog
      cofactors with apoGO.

PMID- 15253156
TI  - Purification of a novel antibacterial short peptide in earthworm Eisenia foetida.
AB  - A novel antimicrobial short peptide was purified from earthworm (Eisenia foetida)
      by a five-step protocol including ammonium sulfate precipitation,
      ultrafiltration, DE-52 ion exchange chromatography, Sephadex G-10 column
      chromatography, and C-18 reversed-phase HPLC techniques. The purified peptide was
      applied to the MALDI-TOP MS to determine the molecular mass and was also
      subjected to TOF MS-MS analysis to determine the amino acid sequence. As a
      result, a novel antibacterial peptide, named OEP3121, was obtained, with the
      molecular mass of 510.8 Da and the sequence being "ACSAG".

PMID- 15253157
TI  - Molecular cloning and characterization of cDNA encoding fibrinolytic enzyme-3
      from earthworm Eisenia foetida.
AB  - The earthworm fibrinolytic enzyme-3 (EFE-3, GenBank accession No: AY438622), from
      the earthworm Eisenia foetida, is a component of earthworm fibrinolytic enzymes.
      In this study, cDNA encoding the EFE-3 was cloned by RT-PCR. The cDNA contained
      an open reading frame of 741 nucleotides, which encoded a deduced protein of 247
      amino acid residues, including signal sequences. EFE-3 showed a high degree of
      homology to earthworm (Lumbricus rebullus) proteases F-III-1, F-III-2, and bovine
      trypsin. The recombinant EFE-3 was expressed in E. coli as inclusion bodies, and
      the gene encoding the native form of EFE-3 was expressed in COS-7 cells in the
      medium. Both the refolding product of inclusion bodies and the secreted protease
      could dissolve the artificial fibrin plate.

PMID- 15253158
TI  - Expression of a modified Cry1Ie gene in E. coli and in transgenic tobacco confers
      resistance to corn borer.
AB  - The wild-type Cry1Ie gene from Bacillus thuringiensis was modified for its
      efficient expression in transgenic plants. Modified Cry1Ie gene (designated as
      Cry1Iem) was cloned into prokaryotic expression vector pET28b and its expression
      in E. coli was confirmed by SDS-PAGE analysis. Bioassays using crude expression
      products in E. coli revealed that Cry1Iem protein had a similar toxicity to corn
      borer as wild-type Cry1Ie. Cry1Iem gene was then inserted downstream of the maize
      ubiquitin-1 promoter in plant expression vector p3301. Transgenic tobacco plants
      carrying Cry1Iem showed insecticidal activity against corn borer.

PMID- 15253159
TI  - [PSA-screening for prostate cancer--yes or no?].
AB  - Prostate cancer is a mayor health care problem, especially in the industrialised
      countries of the Western world. At this time it is the second most common cancer
      reason for death (CH: 1500 men/year) which will even get more importance in the
      future by demographic developments. While there is no doubt that in individuals
      early detection of organ confined disease with localised treatment the prostate
      cancer can be eradicated and individual men be cured there are uncertainties
      whether mass screening a population will contribute to reducing prostate cancer
      related mortality. Its value has not been proved definitively by prospective
      randomised controlled studies. Most of Medical Societies recommend a "well
      informed" decision by family physicians, where the men between 50-70 years know
      about the benefits and harms including: risk of cancer, diagnostic procedures,
      therapeutic consequences and possible side effects. After agreement of early
      detection a biopsy has to be done directly above a PSA level of 4.0 ng/ml or a
      suspicious digital rectal examination. A PSA "grey zone" 4-10 ng/ml can not
      further be postulated. The ratio of free/total PSA gives no support to prolong
      biopsy in this moment, because an elevated benign prostate with a higher
      production of free PSA can mask the tumor in the peripheral zone. Results of the
      ERSPC and the PLCO trials are expected to give information about the benefits and
      harms of mass screening in 2006/8.

PMID- 15253160
TI  - [Aromatase inhibitors in the adjuvant therapy of breast carcinomas].
AB  - Hormonal therapies have been used in the adjuvant therapy of breast cancer for
      decades. Tamoxifen, a selective estrogen receptor modulator, is the current
      standard therapy. It reduces the risk of recurrence by about one half Only
      recently, new aromatase inhibitors (anastrozole, letrozole, exemestane) have been
      competing with tamoxifen; these drugs are superior to tamoxifen in advanced
      breast cancer. Two recent trials are discussed: Anastrozole reduced the short
      term risk of recurrent disease more efficiently than tamoxifen. The use of
      letrozole after five years of adjuvant tamoxifen treatment further reduced the
      risk of recurrence. Numerous side-effects, notably endometrial cancer and
      thromboembolic disease, were less frequent with aromatase inhibitors whereas the
      risk of osteoporotic fractures increased substantially. The positive preliminary
      results of these and other trials are discussed: At present, the use of aromatase
      inhibitors is not yet recommended on a routine basis. Future trial results will
      allow a more complete assessment of the efficacy and toxicity of aromatase
      inhibitors.

PMID- 15253161
TI  - [Molecular therapy in lung cancer].
AB  - Every year more than 370,000 new cases of lung cancer occur in Europe. About 70%
      of the patients are not curable because of local or distant spread of tumor
      cells. Despite the use of chemotherapy, median survival of these patients is less
      than one year In the last two decades, important advances in cancer research have
      been achieved. This led to the development of a new class of potential anti
      cancer agents, selectively targeting molecules which are important for the growth
      and the spread of tumor cells. Focussing on lung cancer, this review presents
      compounds that are furthest in clinical development, covering epidermal growth
      factor receptor inhibitors, receptor tyrosin kinase inhibitors, anti-angiogenic
      agents, matrix metalloproteinase inhibitors, gene therapy and antisense therapy.

PMID- 15253162
TI  - [New therapy options in colorectal carcinoma].
AB  - The introduction of new agents improved chemotherapeutic options in colorectal
      cancer. Combination therapy with irinotecan or oxaliplatin, both with infusional
      5-FU and folinic acid increased response rates to ca. 50% and prolongs--with
      effective second line therapy--median overall survival to 20 months in patients
      with metastatic colorectal cancer. Furthermore, the increased response rates
      allow neoadjuvant treatment of liver metastasis with the aim of a secondary'
      resection of liver metastasis. Oral 5-FU prodrugs (i.e. capecitabine) are a
      convenient alternative but have to prove a comparable efficacy to infusional 5
      FU. The most recent studies investigated monoclonal antibodies in the treatment
      of metastatic colorectal cancer. The additional therapy with the VEGF-antibody
      bevacizumab prolongs survival by more than 4 months compared to chemotherapy
      alone. The EGF-receptor antibody cetuximab is an effective therapy after
      progression with irinotecan.

PMID- 15253163
TI  - [Mabthera for treatment of malignant lymphoma].
AB  - The incidence of Non-Hodgkin Lymphomas (NHL) is rising in the last decades. The
      majority of cases are from the B-cell type, characterized by expression of CD-20.
      Rituximab (Mabthera(r)) is a chimeric monoclonal antibody against CD-20 and has
      revolutionized the treatment of lymphomas of the B-cell phenotype. This antibody
      is generally well tolerated and can be given as an outpatient regimen. As
      monotherapy it has shown good response rates in all CD-20 positive NHL, even in
      patients with multiple prior treatments. The response rates are even higher by
      adding Rituximab maintenance therapy. Excellent results have been achieved by
      combining the antibody with chemotherapy or interferon. In conclusion Rituximab
      has given us interesting new possibilities in the management of patients with Non
      Hodgkin Lymphoma, but the optimal combination, scheduling and duration of this
      therapy still need to be defined. This review gives an overview of the existing
      data of Rituximab treatment in different NHL entities.

PMID- 15253164
TI  - [Allogenic stem cell transplantation following dose-reduced conditioning in
      patients with hematologic systemic diseases or solid tumors].
AB  - Allogeneic stem cell transplantation is an established treatment modality for a
      variety of hematologic malignancies. However this allogeneic stem cell
      transplantation carries the risk of severe complications which are partly due to
      the intensity of the conditioning regimen. Therefore, allogeneic stem cell
      transplantation has been so far only performed in younger patients with good
      performance status. Dose-reduced or non-myeloablative conditioning regimen has
      been proposed as an alternative that would allow exploiting the graft versus
      leukemia effect of allogeneic stem cell transplantation without severe toxicity.
      Clinical studies have shown that dose-reduced conditioning followed by allogeneic
      stem cell transplantation allows stable engraftment with lower toxicities which
      can be associated with long-term disease control. Therefore, dose-reduced
      conditioning followed by allogeneic stem cell transplantation can be offered to
      older and more debilitated patients who were no candidates for standard
      allogeneic stem cell transplantation.

PMID- 15253165
TI  - [Vaccination strategies for solid tumors--fundamentals, limitations, and recent
      results].
AB  - Recent studies clearly prove the existence of cancer immunosurveillance and
      justify renewed hope for the development of effective vaccination therapies for
      solid tumors. The identification of tumor-associated antigens has provided
      researchers with promising targets for T cell-based immunotherapies. New
      monitoring techniques will facilitate the correlation of immunological
      effectiveness of vaccination strategies with clinical results. In order to
      acchieve greater immunological effectiveness, a tumor vaccine should incorporate
      both CD4+ and CD8+ epitopes. Adjuvants should be systematically tested for their
      potential to break immunological tolerance and mechanisms that enable cancer
      cells to escape from immunosurveillance should be further investigated. This
      approach will open new perspectives in the development of tumor vaccines for
      solid tumors. At the same time, future vaccination studies should include
      patients in earlier stages of their disease or in the adjuvant setting in order
      to avoid on overwhelming effect of mechanisms that help tumors to evade
      immunosurveillance.

PMID- 15253166
TI  - The use of complementary and alternative medicine among pediatric patients.
AB  - The overall objective of this research was to obtain information through the use
      of open-ended interviews, about the diagnosis and treatment of children who had
      cancer. The interviews, completed with 29 parents whose children had been
      diagnosed with cancer within the previous 5-year period, were designed to allow
      mothers and fathers to share their experiences about childhood cancer. From this
      process, many salient issues were identified by the interviewed parents, one of
      these issues being that of complementary and alternative medicine (CAM) use among
      children being treated for cancer. Analysis of the CAM theme resulted in the
      identification of the following subthemes: (1) parents' opposition to CAM
      utilization; (2) parents' support of CAM use with their children with cancer; and
      (3) physicians' views of CAM as perceived by parents. Implications for the use or
      nonuse of CAM among pediatric populations will be discussed.

PMID- 15253167
TI  - Gender differences in the use of coping strategies among Taiwanese parents whose
      children have cancer.
AB  - This study explores parental gender-based similarities and differences in the use
      of coping strategies when their children suffer from cancer. The data from the
      171 parent-couples who served as subjects for this study were selected from a
      larger data set of surveys from parents whose children were receiving treatment
      or follow-up care for cancer. The results show that no major differences were
      found between fathers and mothers in coping behaviors while caring for children
      with cancer. In addition to quantitative measure of coping behaviors, a
      qualitative orientation with more in-depth data is needed to explore how parents
      cope with children with cancer. More data are needed on additional variables that
      may influence coping such as the presence and severity of child's illness. Nurses
      need to be aware of the various coping behaviors that mothers and fathers use
      while caring for children with cancer. Assessment of coping strategies is a
      prerequisite to planning care for parents with cancer.

PMID- 15253168
TI  - Exercise decisions within the context of multiple myeloma, transplant, and
      fatigue.
AB  - This constructivist (naturalistic) study explored the decision-making strategies
      of patients with multiple myeloma who were implementing a home-based exercise
      program intended to decrease cancer-related fatigue during therapy. A purposive
      nonprobability sample of 21 patients who were undergoing an aggressive tandem
      transplant protocol provided data through face-to-face and follow-up telephone
      interviews. Salient themes derived from the data through content analysis and
      constant comparison included intrinsic and extrinsic facilitators and barriers
      that influenced the participants' day-to-day decisions about exercise. Intrinsic
      factors that facilitated exercise adherence included a belief that exercise would
      be beneficial, a personal moral/ethical philosophy with regard to honoring a
      commitment and/or taking responsibility for one's health, and personal strategies
      such as keeping a routine and setting goals. Extrinsic facilitators included
      having a good support system and receiving prophylactic epoetin alfa. The
      experience of chemotherapy and related side effects were intrinsic barriers,
      while environmental factors such as weather, travel, and employment could be
      either facilitators or barriers. The delicate balance within the matrix of
      facilitators and barriers influenced participants' daily decisions about
      starting, interrupting, stopping, or resuming their workouts.

PMID- 15253169
TI  - Care diaries: a way of increasing head and neck cancer patient's involvement in
      their own care and the communication between clinicians.
AB  - Head and neck (H&N) cancer patients and their families meet a large number of
      clinicians during their long treatment period and many of them find it difficult
      to understand all the information given concerning their illness, treatment, and
      care. We have developed a care diary for these patients and their families, used
      also by the clinicians involved, to improve communication and patient
      involvement. The present survey was an evaluation of the helpfulness of those
      diaries. Anonymous answered questionnaires were collected from 42 H&N cancer
      patients, 28 family members, and 47 clinicians of different categories.
      Altogether 85% of the respondents stated that the care diaries had a positive
      effect on information, in general, and communication. It is recommended that care
      diaries should be implemented in the standard care for H&N cancer patients and
      their families. To improve the clinical value, it is particularly important to
      inform the clinicians on how to use the care diaries. The content and layout of
      the care diaries needs to be developed according to suggestions given from the
      respondents in this survey.

PMID- 15253170
TI  - Investigating the effects of TTS-fentanyl for cancer pain on the psychological
      status of patients naive to strong opioids: an open label study.
AB  - Few studies have investigated the effect of fentanyl delivered via the
      transdermal route with regard to the patient's psychological status. Patients who
      were naive to strong opioids and were attending a palliative care unit for pain
      relief from advanced cancer participated in this study to determine the effect of
      transdermal therapeutic system fentanyl (TTS-F) on their psychological condition.
      Spielberger State-Trait Anxiety Inventory (STAI), Zung Self-Rating Depression
      Scale (SDS), the Karnofsky Performance Scale (100-0, optimum-death), and a Visual
      Analogue Scale (VAS) (0: no pain; 10: worst pain) were used to measure the level
      of pain. Data were collected at baseline (T0), on the 7th day (T1), and on the
      14th day (T2) of TTS-F application in order to determine changes in correlation
      to TTS-F dose. Patients' status improved according to the Zung SDS questionnaire
      (P < .0005) and with each of its subscales (P < .05). A similar improvement was
      observed according to the Spielberger STAI questionnaire (P = .002). Moreover,
      VAS measures demonstrated that patients achieved significant pain relief (P <
      .0005), while patients' performance status did not alter significantly over the
      study period. Furthermore, the Zung SDS showed a statistically significant
      correlation when compared with the Spielberger STAI (P < .01). These data provide
      some evidence that the psychological status, as measured with respect to
      depression and anxiety in patients with advanced cancer, is improved in patients
      receiving TTS-fentanyl. Future research should use a broad range of psychological
      measurements in order to assist the development of practices, which are aimed at
      the improvement of quality of life in these patients.

PMID- 15253171
TI  - Taking a "leap of faith": acceptance and value of a cancer program-sponsored
      spiritual event.
AB  - Investigations of spiritual interventions for cancer patients are
      disproportionately few compared to the reported importance of religion to
      Americans. We report on the implementation and evaluation of a spiritual,
      community-based intervention developed with interdenominational community clergy.
      Approximately 1200 people attended a total of 3 gatherings: 2 at Roman Catholic
      and another at a Protestant Church. Respondents to questionnaires evaluating
      attendee characteristics and satisfaction (n = 209) were predominantly women
      (85%); 50% were patients and 45% were aged 60 years and older. Men were more
      likely to be currently under treatment for cancer, while women were more likely
      to be past patients or friends. Fewer than 2% felt anger or anxiety; attendees
      felt the service was very (90%) or somewhat (9.5%) helpful and expressed
      appreciation for cancer program clinician attendance and for hospital sponsorship
      of the event. Components in order of preference were prayer, music, Scripture,
      and litany. Logistic regression models reveal that music was most appreciated by
      previously treated patients, and prayer by currently treated patients. Secular
      healthcare systems can offer a religious service that comforts and links
      attendees to a broader community, including clergy and cancer program clinicians.
      Surveys can identify service components that appeal to differing groups and can
      facilitate service development.

PMID- 15253172
TI  - Measurement of symptom distress in women with early-stage breast cancer.
AB  - While symptom distress can alter the cancer experience, it is difficult to define
      and measure. This study's aims were (1) to determine whether the McCorkle Symptom
      Distress Scale (SDS) or the Rhodes Adapted Symptom Distress Scale (ASDS) was the
      more accurate measure of symptom distress in women with breast cancer; (2)
      correlate both scales with a visual analogue scale (VAS) measuring anxiety, a
      symptom frequently reported clinically; (3) determine tool preference; and (4)
      establish when during the first cycle of chemotherapy the highest levels of
      symptom distress were experienced. One hundred twenty women were recruited and
      measurement of symptom distress (SDS and ASDS) and anxiety (VAS) taken at the
      start of chemotherapy (Time 1), at the nadir (Time 2), and at the end of the
      cycle (Time 3). Both instruments were highly correlated and detected change over
      time; none was correlated with the VAS anxiety scale. Symptom distress scores
      were generally low, with fatigue, appearance, insomnia, and concentration causing
      the greatest distress. Other factors like functioning, body image, and menopausal
      symptoms cited as contributors to symptom distress levels were not measured and
      could account for low scores and perhaps suggest that symptom distress may not be
      accurately measured in today's women with early-stage breast cancer.

PMID- 15253173
TI  - Assessment of fatigue in and care needs of Turkish women with breast cancer.
AB  - Using Piper's Integrated Fatigue Model, this research project was planned to
      determine the level of fatigue experienced by Turkish women with breast cancer
      undergoing adjuvant chemotherapy, to discover the factors affecting fatigue, and
      to provide a reference by means of which an effective nursing care for such
      patients could be planned. In assessing the level of fatigue and factors
      affecting it, a patient information form, the Piper Fatigue Scale, and the
      Rotterdam Symptom Checklist were used. The reliability tests performed afterwards
      showed that the scales are appropriate tools for use in Turkish women with breast
      cancer. Before treatment, psychological symptoms' distress was higher than
      physical symptoms' distress. However, following treatment, the latter was found
      to be closer to the former. When pretreatment and posttreatment physical and
      psychological symptoms were compared, it was noticed that fatigue, nausea,
      anorexia, vomiting, constipation, depression, and loss of hope for the future
      were among the symptoms observed to increase the most in the posttreatment
      period. Different from the other studies, we determined that all of the patients
      experienced fatigue 7 to 10 days after the chemotherapy cycle and the
      sensory/affective fatigue scores were high. Breast cancer patients undergoing
      chemotherapy experienced a moderate level of fatigue, which was influenced by
      level of income, stage of disease, and symptoms related to chemotherapy, showing
      compliance with similar studies. Following up patients individually and keeping
      the treatment-related symptoms under control were noticed to help prevent
      fatigue.

PMID- 15253174
TI  - Computerized training in breast self-examination: a test in a community health
      center.
AB  - Fifty-eight women recruited from a community health center completed either a
      brief interactive multimedia training program on breast self-examination using a
      breast model and computer guided feedback on accuracy of lump detection or read a
      National Cancer Institute pamphlet on breast self-examination and breast lumps.
      Women using the computer program as compared to the pamphlet group reported a
      higher sense of self-efficacy for being able to perform a breast self-examination
      immediately after their educational session and 1 month later. However, the
      increase in self-efficacy for the computer group diminished over 4 weeks,
      underscoring the importance of an environment that reminds and reinforces
      learning for women about the performance of regular breast self-examination. The
      increase in sense of self-efficacy to perform breast self-examination with
      roughly 20 minutes of computer-based training and the partial maintenance of that
      self-efficacy 30 days later suggests the utility of incorporating short, focused
      interventions in busy primary healthcare settings.

PMID- 15253175
TI  - Assessing the support needs of women with early breast cancer in Australia.
AB  - The purpose of the current study was to access the degree to which the support
      needs of women with a newly diagnosed, early invasive, primary breast cancer and
      their families are being met. A random sample of 544 women diagnosed with early
      breast cancer was recruited to participate in a telephone survey via state and
      territory cancer registries. Sixteen percent of women reported not receiving
      enough support during their diagnosis and treatment, and only 65% of these women
      reported that their families received enough support. The primary sources of
      support for women and their families were medical practitioners (eg, surgeons,
      oncologists, and general practitioner) with very few women or family members
      utilizing mental health professionals. Given the importance of adequate support
      when being diagnosed and treated for breast cancer, urgent attention needs to be
      paid to training medical professionals in providing appropriate support and
      referrals for their patients.

PMID- 15253176
TI  - Molecular analysis of patients with synostotic frontal plagiocephaly (unilateral
      coronal synostosis).
AB  - Mutations in genes known to be responsible for most of the recognizable syndromes
      associated with bilateral coronal synostosis can be detected by molecular
      testing. The genetic alterations that could cause unilateral coronal synostosis
      are more elusive. It is recognized that FGFR and TWIST mutations can give rise to
      either bilateral or unilateral coronal synostosis, even in the same family. The
      authors undertook a prospective study of patients presenting with synostotic
      frontal plagiocephaly (unilateral coronal synostosis) to Children's Hospital
      Boston during the period from 1997 to 2000. Mutational analysis was performed on
      all patients and on selected parents whenever familial transmission was
      suspected. Intraoperative anthropometry was used in an effort to differentiate
      those patients in whom a mutation was detected from those in whom it was not. The
      anthropometric measures included bilateral sagittal orbital-globe distance, inter
      medial canthal distance, and nasal angulation. Macrocephaly and palpebral
      angulation were also considered possible determinants. There was a 2:1 female
      preponderance in 47 patients with synostotic frontal plagiocephaly. Mutations
      were found in eight of 47 patients: two patients with different single-amino-acid
      changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with
      TWIST mutations. Another patient had craniofrontonasal syndrome for which a
      causative locus has been mapped to chromosome X, although molecular testing is
      not yet available. Two features were strongly associated with a detectable
      mutation in patients with synostotic frontal plagiocephaly: asymmetrical
      brachycephaly (retrusion of both supraorbital rims) and orbital hypertelorism.
      Other abnormalities in the craniofacial region and extremities were clues to a
      particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. Neither
      macrocephaly nor degree of nasal angulation nor relative vertical position of the
      lateral canthi correlated with mutational detection. An additional four patients
      in this study had either unilateral or bilateral coronal synostosis in an
      immediate relative and had anthropometric findings that predicted a mutation, and
      yet no genetic alteration was found. This suggests either that the authors'
      screening methods were not sufficiently sensitive or that perhaps there are other
      unknown pathogenic loci. Nevertheless, molecular testing is recommended for
      infants who have unilateral coronal synostosis, particularly if there are the
      anthropometric findings highlighted in this study or an otherwise suspicious
      feature in the child or a parent. Infants with either an identified or a
      suspected mutation usually need bilateral asymmetric advancement of the bandeau
      and may be more likely to require frontal revision in childhood.

PMID- 15253177
TI  - Removal of mandibular tooth follicles before distraction osteogenesis.
AB  - Distraction osteogenesis is an innovative technique that has transformed the
      treatment of craniofacial malformations in young children. Bone generation
      obviates the need for graft material, which is in short supply in young patients,
      thus making possible surgical procedures on the craniofacial skeleton in young
      children. Sufficient mandibular volume is required for the osteotomy and
      placement of the device screws and/or pins. To have adequate bone stock and to
      facilitate distraction, the authors preoperatively examined all patients
      radiographically and selected those with tooth follicles that precluded
      successful osteotomy and pin placement for planned mandibular distraction. This
      report is of the first 13 children, aged 9 months to 6 years, who underwent
      predistraction enucleation. The osteotomy and device placement were performed
      successfully at least 4 months after enucleation. The described procedure has
      minimal morbidity and has resulted in successful subsequent distraction. The
      advantages, disadvantages, and cost-benefit issues are discussed.

PMID- 15253178
TI  - Bowel preparation before microvascular free colon transfer for head and neck
      reconstruction: is it necessary?
AB  - Mechanical bowel preparation before any intestinal operation, especially when the
      large intestine is involved, is routine practice for most surgeons. This practice
      has been questioned by many colorectal surgeons, with convincing data showing the
      lack of benefit of preoperative mechanical bowel preparation. Free microvascular
      transfer of the large intestine is occasionally performed for reconstruction of
      the upper esophagus, as it provides a better size match for the oropharynx than
      other visceral organs. Nine patients underwent reconstruction of the cervical
      esophagus and voice tube using a segment of ileocolon. In all patients, the
      cervical esophagus was reconstructed using the ascending colon and the voice tube
      was reconstructed using the ileal segment. Both were transferred as one free
      flap. All patients underwent the procedure without any form of preoperative
      mechanical bowel preparation. The patients were able to tolerate a solid diet at
      the end of the mean follow-up period of 7 months, and all esophagograms showed no
      evidence of stricture formation. One patient developed a fistula at the recipient
      site that was treated with a regional flap, one patient developed a superficial
      wound infection of the abdominal wall, and one patient developed a postoperative
      abdominal wound dehiscence after several episodes of excessive coughing.
      Microvascular transfer of a large intestinal segment without preoperative
      mechanical bowel preparation for the reconstruction of the esophagus is a safe
      procedure. It can avoid the discomfort and complications associated with
      mechanical bowel preparation. If preoperative mechanical bowel preparation is
      preferred, the results of this study, which are based on nine patients,
      demonstrate the safety of this practice in cases where the patient did not follow
      proper instructions or in cases where the use of the colon was not anticipated
      preoperatively.

PMID- 15253179
TI  - Clinical and basic research on occipito-cervico-dorsal flaps: including a study
      of the anatomical territories of dorsal trunk vessels.
AB  - The authors have carried out a clinical study of all the patients who underwent
      reconstructions with occipito-cervico-dorsal flaps in their department between
      1994 and 2003 and analyzed the outcomes of the surgery. The reconstructed areas
      ranged from the cheek to the anterior chest. Twenty-eight cases underwent
      reconstruction with microvascular augmented occipito-cervico-dorsal flaps, and
      four were reconstructed with single pedicle occipito-cervico-dorsal flaps. In
      five cases, distal partial necrosis was observed. The largest flap size was 43 x
      23 cm (5 x 5-cm pedicle). In the microvascular augmented occipito-cervico-dorsal
      flaps, the circumflex scapular artery and veins were used in 28 cases, and dorsal
      intercostal perforators were used together with circumflex scapular artery and
      veins in five cases. The follow-up term was between 1 and 8 years. Neck scar
      contractures were released in all cases, and good results were obtained not only
      functionally but also aesthetically. In an anatomical study, the authors used 20
      preserved cadavers and took angiograms of the dorsal region. Five cadavers were
      used to confirm the territory of each of the vessels that have close relations to
      the occipito-cervico-dorsal flap (the occipital artery, transverse cervical
      artery, circumflex scapular artery, and dorsal intercostal perforator artery).
      Each anatomical territory was clearly seen and its area identified.

PMID- 15253180
TI  - Importance of additional microvascular anastomosis in esophageal reconstruction
      after salvage esophagectomy.
AB  - Esophageal reconstruction after salvage esophagectomy in patients who have
      undergone curative-intent chemoradiotherapy for esophageal cancer is associated
      with a significant risk of perioperative morbidity and mortality. In particular,
      anastomotic leakage can cause severe and potentially fatal complications,
      including mediastinitis and pneumonia. The authors performed esophageal
      reconstruction with a pedicled right colon graft after salvage esophagectomy in
      eight patients. To decrease the rate of anastomotic leakage, the authors
      performed an additional microvascular anastomosis at the distal end of the graft.
      The distal stumps of the ileocolic artery and vein were anastomosed to the
      cervical vessels. After surgery, aspiration pneumonia and localized wound
      infection were observed in two patients each, but slight anastomotic leakage was
      observed in only one patient. Postoperative swallowing function was satisfactory
      in all patients. Although the incidence of anastomotic leakage is reportedly
      high, the authors observed anastomotic leakage in only one of eight patients. The
      authors believe that additional microvascular anastomosis helps prevent
      anastomotic leakage, especially in patients who have undergone salvage
      esophagectomy after curative chemoradiotherapy.

PMID- 15253181
TI  - Surgical management of parotid hemangioma.
AB  - Hemangiomas represent one of the most common childhood neoplasms. They are often
      managed conservatively, requiring numerous years for spontaneous involution. No
      effective medical treatment has been reported for children with large, deforming
      hemangiomas of the parotid gland and overlying cheek. The authors retrospectively
      studied 17 children who underwent surgical resection of parotid hemangiomas at
      Childrens Hospital Los Angeles from 1997 to 2003. All 17 patients had
      improvements in facial asymmetry and deformity. There were no major
      complications. Minor complications included hematoma (11.8 percent), transient
      facial nerve palsy (11.8 percent), and blood transfusion (5.9 percent). All
      operations were performed on an outpatient basis. Surgical resection of parotid
      hemangiomas provides an aesthetic benefit to young children with low associated
      morbidity. Early resection by an experienced surgeon should be considered as a
      treatment option for these disfiguring lesions.

PMID- 15253182
TI  - Importance of coronoidotomy and masticatory muscle myotomy in surgical release of
      trismus caused by submucous fibrosis.
AB  - Thirty patients with trismus resulting from betel nut chewing-induced oral
      submucous fibrosis were treated with either fibrotic tissue release only (group
      I) or fibrotic tissue release in combination with masticatory muscle myotomy and
      coronoidotomy (group II). The latter procedures were only performed in patients
      whose intraoperative interincisal distance remained less than 35 mm immediately
      after submucous fibrous tissue release. There were eight and 22 patients in
      groups I and II, respectively. In group I patients, the average intraoperative
      interincisal distance improved from 19.5 mm to 42 mm. In group II patients, the
      average intraoperative interincisal distance improved from 13.5 mm to 27 mm after
      fibrotic tissue release and further improved to 40 mm after masticatory muscle
      myotomy and coronoidotomy. At an average follow-up of 22.1 months (range, 7 to 70
      months), the group I and II patients had an average interincisal distance of 41.5
      mm (range, 35 to 50 mm) and 32.9 mm (range, 20 to 42 mm), respectively. These
      results demonstrate the efficacy of submucous fibrotic tissue release in treating
      trismus resulting from betel nut chewing-induced submucous fibrosis and confirm
      the role of additional masticatory muscle and coronoidotomy in treating its
      severe forms.

PMID- 15253183
TI  - Dissociative anesthesia for safety's sake: ketamine and diazepam--a 35-year
      personal experience.
AB  - Recent discussions and proposed rules and regulations regarding outpatient
      surgery facilities have raised the question of the appropriateness of general
      anesthesia versus heavy sedation. The controversy is based mostly on anecdotal
      information and the prejudice of the authors. A recent article that describes the
      improved platelet function induced by ketamine adds patient safety to the
      rationale for sedation. Most of us have trained in university settings where an
      entire department was devoted to general anesthesia and little true outpatient
      surgery was performed. When ambulatory facilities were available, they were
      usually staffed by anesthesiologists. Indeed, the first free-standing outpatient
      surgery center in Phoenix, Arizona, was owned and operated by a local group of
      anesthesiologists. Properly administered, diazepam and ketamine dissociative
      sedation is safe and effective for every aesthetic procedure, regardless of size
      or duration, and it should be available for all aesthetic surgeons. In the
      author's experience, more than 30,000 procedures have been performed with this
      method since 1966 without a single case of deep vein thrombosis or pulmonary
      embolus. In contrast, a former associate, because of his lack of experience,
      chose to use general anesthesia for a few larger cases in another facility. One
      of those cases, an abdominoplasty, resulted in a serious case of deep vein
      thrombosis with subsequent alleged disability and litigation. Therefore, the
      author is writing to share his extensive experience with his colleagues in hopes
      that these safe systems will become more widespread and to spare future patients
      the attendant unnecessary increased morbidity and mortality associated with
      general anesthesia.

PMID- 15253184
TI  - The patient and observer scar assessment scale: a reliable and feasible tool for
      scar evaluation.
AB  - At present, various scar assessment scales are available, but not one has been
      shown to be reliable, consistent, feasible, and valid at the same time.
      Furthermore, the existing scar assessment scales appear to attach little weight
      to the opinion of the patient. The newly developed Patient and Observer Scar
      Assessment Scale consists of two numeric scales: the Patient Scar Assessment
      Scale (patient scale) and the Observer Scar Assessment Scale (observer scale).
      The patient and observer scales have to be completed by the patient and the
      observer, respectively. The patient scale's consistency and the observer scale's
      consistency, reliability, and feasibility were tested. For the Vancouver Scar
      Scale, which is the most frequently used scar assessment scale at present, the
      same statistical measurements were examined and the results of the observer scale
      and the Vancouver scale were compared. The concurrent validity of the observer
      scale was tested with a correlation to the Vancouver scale. Furthermore, the
      authors examined which specific characteristics significantly influence the
      general opinion of the patient and the observers on the scar areas. Four
      independent observers have each used the observer scale and the Vancouver scale
      to assess 49 burn scar areas of 3 x 3 cm belonging to 20 different patients.
      Subsequently, the patients completed the patient scale for their scar areas. The
      (internal) consistency of both the patient and the observer scales was acceptable
      (Cronbach's alpha, 0.76 and 0.69, respectively), whereas the consistency of the
      Vancouver scale appeared not to be acceptable (alpha, 0.49). The reliability of
      the observer scale completed by a single observer was acceptable (r = 0.73). The
      reliability of the Vancouver scale completed by a single observer was lower (r =
      0.69). The observer scale showed better agreement than the Vancouver scale
      because the coefficient of variation was lower (18 percent and 22 percent,
      respectively). The concurrent validity of the observer scale in relation to the
      Vancouver scale is high (r = 0.89, p < 0.001). Linear regression of the general
      opinions on scars of the observer and the patient showed that the observer's
      opinion is influenced by vascularization, thickness, pigmentation, and relief,
      whereas the patient's opinion is mainly influenced by itching and the thickness
      of the scar. Such an impact of itching and thickness of the scar on the patient's
      opinion is an important and novel finding. The Patient and Observer Scar
      Assessment Scale offers a suitable, reliable, and complete scar evaluation tool.

PMID- 15253185
TI  - Risk of melanoma arising in large congenital melanocytic nevi: a systematic
      review.
AB  - Large congenital melanocytic nevi are cutaneous lesions regarded by many as
      premalignant; estimates of malignancy incidence range from 0 to 42 percent. Given
      the often complex and extensive nature of large congenital melanocytic nevi
      resection and reconstruction, the risk of malignant transformation is a crucial
      factor that surgeons and families must weigh when deciding whether or not to
      excise the lesion. The authors conducted a systematic analysis of data from the
      existing literature to critically evaluate the published studies and to establish
      a crude incidence rate for the risk of malignant melanoma transformation in large
      congenital melanocytic nevi. After a comprehensive literature search, they
      analyzed data from eight studies (containing a total of 432 large congenital
      melanocytic nevi patients) of sufficient scientific quality. Twelve patients (2.8
      percent) in this sample developed cutaneous malignant melanoma during the
      reported follow-up periods. Using a subset of this data and comparing the
      incidence rates to those of the Surveillance, Epidemiology, and End Results
      population-based database using a standardized morbidity ratio, the authors found
      that the large congenital melanocytic nevi patients had an increased risk of
      melanoma (standardized morbidity ratio, 2599; 95 percent confidence interval, 844
      to 6064) compared with the general population. Regarding treatment before
      developing melanoma in the 12 patients, 50 percent were observed before
      diagnosis, 17 percent had partial excision, 8.3 percent had dermabrasion, 8.3
      percent had a chemical peel, and 17 percent did not have any treatment
      information. These combined data are clinically useful when consulting with the
      parents of children with large congenital melanocytic nevi and in the management
      of older patients with existing lesions. This study shows that there is a
      significantly increased risk of melanoma in large congenital melanocytic nevi
      patients. The data also reveal the need for a standardized definition of large
      congenital melanocytic nevi and a long-term, prospective outcomes study to
      determine the true lifetime risk of melanoma in patients with and without
      surgical excision.

PMID- 15253186
TI  - Evaluation of breast sensibility using dermatomal somatosensory evoked
      potentials.
AB  - This study was undertaken to prospectively evaluate breast sensibility before and
      after reduction mammaplasty with a new, objective, and quantitative
      neurophysiologic method based on the anatomic knowledge of breast innervation and
      the congruent areas of dermatomal maps. An innovative application of dermatomal
      somatosensory evoked potentials was used to study the breast regions of 42
      healthy women, bilaterally. The areas stimulated in each breast were the superior
      quadrant, the nipple-areola complex and the medial and lateral quadrants, and the
      inferior quadrant; these areas correspond to T3, T4, and T5 dermatomes,
      respectively, following the accepted concepts of segmentary innervation of the
      skin. The two groups of 21 patients each were formed according to breast size:
      group I comprised small-breasted, unoperated controls (brassiere cup size A or
      B); group II comprised macromastia patients (brassiere cup size C or greater) who
      presented to a general plastic surgery department for breast reduction surgery.
      First the authors established the normal range of latency and amplitude in the
      dermatomal somatosensory evoked potentials for the five areas stimulated in
      patients with small breasts and compared these parameters with those obtained
      from patients with macromastia. Then, after the macromastia patients underwent
      reduction mammaplasty using the McKissock technique, the authors compared the
      postoperative sensory values with their own preoperative values and with those
      from the small-breasted group. Using dermatomal somatosensory evoked potentials,
      they found that small breasts were statistically more sensitive than large
      breasts, which concurs with studies in the literature that use other methods to
      evaluate breast sensibility. They also found that after breast reduction, the
      macromastia patients presented statistically significant improvement in breast
      sensibility in relation to their own preoperative latency and amplitude values,
      with no statistical difference in amplitude with respect to the small-breasted
      group; this finding suggests that after breast reduction, sensibility similar to
      that of the small-breasted group can be considered a possibility. Furthermore, in
      comparisons of each of the five areas stimulated, there was no significant
      difference in values within the small-breasted group or within the macromastia
      group before or after surgery; this supports a possible overlap between adjacent
      dermatomes. This innovative application of dermatomal somatosensory evoked
      potentials is an objective, quantitative, and noninvasive method that has allowed
      the authors to evaluate breast sensibility and to compare postsurgical sensory
      outcomes.

PMID- 15253187
TI  - Occult breast carcinoma in reduction mammaplasty specimens: 14-year experience.
AB  - Reduction mammaplasty is commonly performed for bilateral macromastia, congenital
      asymmetry, or as a contralateral symmetry procedure in breast reconstruction
      following mastectomy for cancer. Occult carcinoma has been detected in 0.06
      percent to 0.4 percent of breast reduction specimens. The purpose of this study
      was to examine the incidence of breast cancer in breast reductions performed in
      one institution over a 14-year period. The authors reviewed their experience with
      800 reduction mammaplasties performed between 1988 and 2001. Six cancers were
      detected (0.8 percent). Of these cancers, three were invasive (0.4 percent) and
      three were ductal carcinoma in situ (0.4 percent). Stratified by indication for
      surgery, there was a trend toward higher detection rates in the reconstruction
      group (1.2 percent) compared with the macromastia (0.7 percent) or congenital
      asymmetry (0 percent) groups. Mammography was performed preoperatively in these
      patients and all results were negative for masses or suspicious
      microcalcification. Pathological diagnosis was guided by gross specimen
      evaluation in two patients and specimen radiography in one patient. Reduction
      mammaplasty has a small but definite risk of finding cancer in the resection
      specimen.

PMID- 15253188
TI  - Free fibula long bone reconstruction in orthopedic oncology: a surgical algorithm
      for reconstructive options.
AB  - The fibula free flap became popular in orthopedic oncology for limb-sparing long
      bone tumor resection. It is particularly suitable for intercalary or resection
      arthrodesis options. In the present series, a surgical reconstruction algorithm
      was used, enabling each patient to receive a personalized technique. During the
      years 1998 to 2002, 30 patients underwent limb-sparing surgery for long bone
      sarcoma. There were 18 males and 12 females. Their mean age was 23 years (range,
      9 to 70 years). The diagnoses were Ewing's sarcoma (11 patients), osteogenic
      sarcoma (eight patients), chondrosarcoma (five patients), giant cell tumor of
      bone (three patients), high-grade soft-tissue sarcoma (two patients), and
      leiomyosarcoma of bone (one patient). The majority of tumors where located in the
      lower extremity (23 patients), mostly in the femur (15 patients with four tumors
      in the proximal femoral shaft, five tumors in the distal femoral shaft, five
      tumors in the whole femoral shaft, and one tumor in the proximal femoral head).
      In seven patients, the upper extremity was involved; in six patients, the radius
      was involved; and in one patient, the humerus was involved. The free fibula flap
      was used in three types of approaches: vascularized fibula as an osseous flap
      only (18 patients), a combination of a vascularized fibula flap in conjunction
      with an allograft (Capanna's technique; 10 patients), and a free double-barreled
      fibula (two patients). All flaps survived. Postoperatively, all patients were
      monitored clinically, radiologically, and by radioisotope bone scan studies.
      Callus formation and union were shown 2.6 to 8 months postoperatively. Patients
      who underwent lower extremity reconstruction were nonweightbearing for 3 to 9
      months, with a transition period in which they used a brace and gradually
      increased weightbearing until full weightbearing was achieved. Eight patients had
      11 recipient-site complications. Two patients (6.7 percent) had hematomas, and
      three patients (10 percent) had infection and dehiscence of the surgical wound
      with bone exposure in one patient; all complications resolved with conservative
      treatment only. Failure of the hardware fixation system occurred in two patients,
      mandating surgical correction. No fibula donor-site complications were recorded.
      In intercalary resections, the use of the vascularized fibula flap as an isolated
      osseous flap might be insufficient. Different body sites have different stress
      loads to carry, depending on the age of the patient and on his individual
      physical status. To achieve initial strength in the early period, the authors
      combined the free fibula flap with an allograft (Capanna's method) or augmented
      it as a double-barreled fibula. They propose a surgical algorithm to assist the
      surgeon with the preferred method for reconstruction of various long bone defects
      in different body locations at childhood or adulthood. Long bone reconstruction
      using a vascularized fibula flap, alone or in combination with an allograft,
      autogenous bone graft, or double-barreled fibula for limb-sparing surgery, is a
      safe and reliable method with a predictable bony union, good functional outcome,
      and a low complication rate.

PMID- 15253189
TI  - The subscapular arterial tree as a source of microvascular arterial grafts.
AB  - The subscapular arterial tree may be used as a source of microvascular grafts to
      replace damaged or diseased portions of arteries, particularly in the hand and
      forearm. By studying cadaver dissections, it is possible to estimate the number
      of branches that may be found at different arterial segment lengths from the
      origin of the subscapular artery. Fifty-five preserved cadaver subscapular
      arterial trees were dissected, and the branching patterns were documented. Three
      major arterial branching patterns of the subscapular artery were observed with
      one, two, and three major branches to the serratus anterior in 60 percent, 29
      percent, and 9 percent of the cases, respectively. The authors determined the
      number of 1-mm-diameter, 1-cm-long branches arising from each of six 3-cm regions
      of the arterial tree measured from the origin of the subscapular artery to the
      end of the longest terminal branch. The probability of finding at least one
      usable terminal branch that is at least 12.0 cm in length was found to be 98
      percent. Typically, there are two to five useful branches at this distance. Such
      information may help surgeons fine tune their process of selecting an appropriate
      arterial donor site for a particular arterial defect and supports the use of the
      subscapular arterial tree as a donor site for microvascular arterial grafts.

PMID- 15253190
TI  - Free tissue transfer in patients with renal disease.
AB  - Several authors have cited renal disease as a risk factor for free flap failure.
      The authors performed a retrospective analysis of all patients who underwent free
      tissue transfer with concomitant renal disease, including acute renal failure,
      end-stage renal disease, chronic renal insufficiency, and functional kidney
      transplants, to determine what effect renal disease has on flap survival and
      overall reconstructive outcome. More than 1053 free flaps were examined. Renal
      disease was identified in 32 patients who underwent 33 free tissue transfers.
      Average patient age was 57 years (range, 36 to 80 years). Twelve patients (38
      percent) were on chronic dialysis (end-stage renal disease), 18 patients (56
      percent) had chronic renal insufficiency, and three patients (9 percent) had the
      diagnosis of acute renal failure at the time of surgery. Three patients in the
      chronic renal insufficiency group had a functioning renal transplant. Average
      follow-up was 16 months. Immediate postoperative complications occurred in 14
      patients (42 percent of the 33 flaps). Overall perioperative mortality was 3
      percent. Within the first 30 days there were two cases (6 percent) of primary
      flap failure; an additional four legs were lost as the result of complications
      related to their bypass grafts. There were no primary flap failures after 30
      days; however, within the first year after surgery an additional seven limbs were
      lost as the result of progressive ischemia or infection, and an additional three
      patients died. This resulted in a 52 percent incidence of major morbidity or
      mortality during the first year and a 55 percent reconstructive success rate in
      survivors at 1 year. No significant difference was seen in postoperative
      morbidity or mortality when comparing the end-stage renal disease group to the
      chronic renal insufficiency group; however, patients with renal disease and
      diabetes tended to have poorer outcomes. Renal disease, especially renal disease
      associated with diabetes and peripheral vascular disease, can be a strong
      indicator of possible reconstructive failure. The surgeon and patient should be
      aware of the medical and surgical complications associated with this procedure at
      the outset.

PMID- 15253191
TI  - Gluteal perforator flaps for coverage of pressure sores at various locations.
AB  - Flap coverage is essential for successful treatment of pressure sores, and
      musculocutaneous flaps have been preferred universally. Development of perforator
      flaps supplied by musculocutaneous perforators has allowed reconstructive
      surgeons to harvest flaps without including muscles. Perforator flaps have
      enhanced the possibility of donor sites because a flap can be supplied by any
      musculocutaneous perforator, and donor-site morbidity is also reduced. Between
      November of 1998 and June of 2002, the authors used 35 gluteal perforator flaps
      in 32 consecutive patients for coverage of pressure sores located at sacral (n =
      22), ischial (n = 7), and trochanteric (n = 6) regions. The mean age of the
      patients was 53.1 years (range, 5 to 87 years), and there were 16 male and 16
      female patients. All flaps in this series were supplied by musculocutaneous
      arteries arising from gluteal muscles. Patients were followed up for a mean
      period of 13.6 months. Wound dehiscence was observed in two patients and treated
      by secondary closure. Three patients died during the follow-up period. All flaps
      survived except one that had undergone total necrosis, and only one recurrence
      was noted during the follow-up period. Gluteal perforator flaps are safe and
      reliable options for coverage of pressure sores located at different locations.
      Freedom in flap design and low donor-site morbidity make gluteal perforator flaps
      an excellent choice for pressure sore coverage.

PMID- 15253192
TI  - A comparison of flexor tenosynovectomy, open carpal tunnel release, and open
      carpal tunnel release with flexor tenosynovectomy in the treatment of carpal
      tunnel syndrome.
AB  - The purpose of this study was to identify the advantages and disadvantages of
      performing a flexor tenosynovectomy without dividing the transverse carpal
      ligament, an open carpal tunnel release, and an open carpal tunnel release with
      flexor tenosynovectomy in the treatment of carpal tunnel syndrome. From 1990 to
      1998, a retrospective study was done in which a flexor tenosynovectomy was
      performed in 133 patients without division of the transverse carpal ligament and
      compared with 68 patients who had an open carpal tunnel release and 75 patients
      who had an open carpal tunnel release and flexor tenosynovectomy. Patients were
      followed up for an average period of 30 weeks with history and physical findings
      and nerve conduction velocities and for an average period of 2.6 years with
      telephone interviews. There was a 2.3 percent incidence of pillar pain in the
      flexor tenosynovectomy group, which may explain the earlier return to their
      regular jobs at an average time of 9.9 weeks, compared with 10.7 weeks for the
      carpal tunnel release group and 12.0 weeks for the carpal tunnel release/flexor
      tenosynovectomy group. The latter two groups had an incidence of pillar pain of
      12.1 percent and 25.3 percent, respectively. Postoperative grip strength was
      statistically significantly improved in the flexor tenosynovectomy group compared
      with the other two groups, where adjustments were made for sex and preoperative
      grip strengths with standard error of adjusted means. In the flexor
      tenosynovectomy group, 20.6 percent of patients had a previous open or endoscopic
      carpal tunnel release with recurrent carpal tunnel syndrome, compared with 5.2
      percent in the open carpal tunnel release group and 21.6 percent in the open
      carpal tunnel release with flexor tenosynovectomy group. Excisional biopsies of
      flexor tenosynovium in the flexor tenosynovectomy, open carpal tunnel release,
      and open carpal tunnel release with flexor tenosynovectomy groups revealed an
      incidence of fibrosis in 89.2 percent, 88.9 percent, and 87.7 percent of
      specimens, respectively. Edema was a frequent finding, but an active inflammatory
      response was seldom seen. The findings in this study indicate that because of a
      significant decrease in pillar pain, a flexor tenosynovectomy in the treatment of
      carpal tunnel syndrome would likely benefit workers who use the palm of the hand
      in heavy manual or highly repetitive work by allowing them to return to regular
      duty sooner.

PMID- 15253193
TI  - Basic fibroblast growth factor expression following surgical delay of rat
      transverse rectus abdominis myocutaneous flaps.
AB  - Partial transverse rectus abdominis myocutaneous (TRAM) flap loss in breast
      reconstruction can be a devastating complication for both patient and surgeon.
      Surgical delay of the TRAM flap has been shown to improve flap viability and has
      been advocated in "high-risk" patients seeking autogenous breast reconstruction.
      Despite extensive clinical evidence of the effectiveness of surgical delay of
      TRAM flaps, the mechanisms by which the delay phenomenon occurs remain poorly
      understood. To examine whether angiogenic growth factors such as basic fibroblast
      growth factor (bFGF) may play a role in the delay phenomenon, the authors studied
      the expression of bFGF in rat TRAM flaps subjected to surgical delay. Thirty-five
      female Sprague-Dawley rats were randomly assigned to one of four TRAM flap
      groups: no delay (n = 6), 7-day delay (n = 12), 14-day delay (n = 10), or 21-day
      delay (n = 7). Surgical delay consisted of incising skin around the perimeter of
      the planned 2.5 x 5.0-cm TRAM flap followed by ablation of both superior
      epigastric arteries and the left inferior epigastric artery, thus preserving the
      right inferior epigastric artery (the nondominant blood supply to the rectus
      abdominis muscle of the rat). TRAM flaps were then elevated after 7, 14, and 21
      days of delay by raising zones II, III, and IV off the abdominal wall fascia.
      Once hemostasis was assured, the flaps were sutured back in place. All flaps were
      designed with the upper border of the flap 1 cm below the xiphoid tip. Three days
      after the TRAM procedure, postfluorescein planimetry was used to determine
      percent area viability of both superficial and deep portions of TRAM flaps. All
      rats were euthanized and full-thickness TRAM specimens were taken from zones I,
      II, III, and IV for enzyme-linked immunoabsorbent assay analysis of bFGF levels.
      Statistical testing was done by t test (percent viability) and two-way analysis
      of variance (bFGF levels). All delayed flaps had significantly higher bFGF levels
      when compared with all nondelayed control flaps (p < 0.05). The bFGF levels were
      not different in the rats that received TRAM flaps 7, 14, or 21 days after delay
      surgery. There was also no significant difference in bFGF levels among zones I
      through IV. Control rats had more peripheral zone necrosis compared with all
      delayed TRAM rats. All delayed flaps had a significantly higher area of flap
      viability superficially than nondelayed control flaps (p < 0.05). There was no
      difference in deep flap viability. Surgical delay of rat TRAM flaps is associated
      with improved flap viability and significantly elevated levels of bFGF over
      nondelayed TRAM flaps at postoperative day 3 after TRAM surgery. The increases in
      bFGF noted at this time point suggests that bFGF may play a role in the improved
      TRAM flap viability observed after delay surgery. Further investigation is needed
      to evaluate the role bFGF may play in the delay phenomenon.

PMID- 15253194
TI  - Apoptosis in a rodent model of cranial suture fusion: in situ imaging and gene
      expression analysis.
AB  - Craniosynostosis, the premature fusion of cranial sutures, is one of the most
      common craniofacial anomalies, with a reported incidence of up to one in 2500
      live births. Despite its prevalence, the cause of craniosynostosis remains
      unknown. Previously, apoptosis has been postulated to be a contributing factor in
      the pathogenesis of craniosynostosis, although the role of programmed cell death
      in cranial sutures is poorly understood. To address this problem, the authors
      used an established rodent model of posterior-frontal suture fusion and sagittal
      suture patency to globally examine apoptosis in cranial sutures. Apoptosis was
      evaluated by systemically coinjecting Sprague-Dawley rats with both fluorescent
      and technetium-99m-labeled annexin V at time points before, during, and after the
      period of predicted posterior-frontal suture fusion to determine the magnitude
      and time course of overall apoptotic activity in both fusing and patent sutures.
      Using these novel in situ imaging techniques, the authors observed a significant
      increase in the overall levels of apoptosis in both the posterior-frontal and
      sagittal suture complexes during the period of predicted posterior-frontal suture
      fusion. To further explore this increase in apoptotic activity, they used
      microarray technology to study apoptosis-related genes within the suture complex.
      Interestingly, there was activation of distinct apoptotic pathways in the
      posterior-frontal and sagittal sutures during the period of predicted posterior
      frontal suture fusion. Whereas increased transcription of genes associated with
      the mitochondria-mediated apoptotic pathway occurred in the posterior-frontal
      suture during fusion, activation of genes associated with the death receptor
      mediated apoptotic pathway predominated in the patent sagittal suture during the
      same time period. These data suggest that although overall apoptotic activity in
      rat patent and fusing sutures is similar, the pathways mediating apoptosis within
      each suture are distinct.

PMID- 15253196
TI  - Reinnervation of arterial grafts by adrenergic nerves occurs in rats as indicated
      by increased levels of noradrenaline.
AB  - To investigate the changes in noradrenaline concentrations in transplanted
      arterial grafts in rats, 31 female rats 4 to 6 weeks old of the AO/Ks:OC strain
      were operated on. Femoral arterial grafts were anastomosed to carotid arteries
      and compared with control femoral segments. Six rats were included in each follow
      up group at 0, 1, 4, and 12 weeks, and there were seven rats in the 20-week
      follow-up group. High-performance liquid chromatography was used to determine the
      concentrations of noradrenaline. The operation itself decreased noradrenaline
      concentrations in the grafts to 76 percent of that in the control segments. One
      week after the operation, the noradrenaline concentration had fallen to 1.7
      percent of the control values and started to recover thereafter. One month after
      the operation, it was 23 percent; at 3 months, it was 31 percent; and at 5
      months, it was 43 percent of control values. The decrease from time 0 to 1 week
      was significant (p = 0.001), as was the increase from 1 week to 20 weeks (p =
      0.004). Noradrenaline concentrations had fallen significantly 1 week after the
      operation and thereafter they increased to levels comparable to those seen in the
      immediate postoperative period.

PMID- 15253195
TI  - Pharmacologic enhancement of rat skin flap survival with topical oleic acid.
AB  - This study was instituted to investigate in a rat model the effect of topical
      coadministration of the penetration enhancer oleic acid (10% by volume) and RIMSO
      50 (medical grade dimethyl sulfoxide, 50% by volume) on rat skin flap survival. A
      rectangular abdominal skin flap (2.5 x 3 cm) was surgically elevated over the
      left abdomen in 40 nude rats. The vein of the flap's neurovascular pedicle was
      occluded by placement of a microvascular clip, and the flap was resutured with 4
      0 Prolene to its adjacent skin. At the end of 8 hours, the distal edge of the
      flap was reincised to gain access to the clips and the clips were removed. After
      resuturing of the flap's distal edge to its adjacent skin, the 40 flaps were
      randomly divided into four groups. Group 1 (control) flaps were treated with 5 g
      of saline, group 2 (dimethyl sulfoxide) flaps were treated with 2.7 g of dimethyl
      sulfoxide (50% by volume), group 3 flaps (oleic acid) were topically treated with
      0.45 g of oleic acid (10% by volume), and group 4 (dimethyl sulfoxide plus oleic
      acid) flaps were treated with a mixture of 0.45 g of oleic acid (10% by volume)
      and 2.7 g of dimethyl sulfoxide (50% by volume) diluted in saline. Each flap was
      topically treated with 5 ml of drug-soaked gauze for 1 hour immediately after
      clip removal to attenuate reperfusion injury. Thereafter, drug was applied
      topically once daily for 4 more days. Digital photographs of each flap were then
      taken on day 6 and the flaps were then harvested. The percentage of skin survival
      in each flap was determined by computerized morphometry and planimetry. The mean
      surviving area of group 3 (oleic acid-treated flaps) was 23.60 +/- 4.19 percent
      and was statistically higher than that in group 1 (control, saline-treated flaps)
      at 7.20 +/- 2.56 percent. The mean surviving area of group 2 (dimethyl sulfoxide
      treated flaps) at 18.00 +/- 5.23 percent and group 4 (oleic acid- and dimethyl
      sulfoxide-treated flaps) at 9.90 +/- 3.44 percent did not achieve statistically
      higher mean surviving areas than controls. A topical solution of oleic acid (10%
      by volume) caused a statistically significant increase in the survival of rat
      abdominal skin flaps relative to controls. Dimethyl sulfoxide and the two
      experimental drugs together did not increase the percentage of flap survival when
      given as a single 5-ml dose released from a surgical sponge at reperfusion for 1
      hour and then daily for a total of 5 days. The reasons for the lack of response
      are unknown but may have included the technical difficulty of delivering an
      adequate dose of dimethyl sulfoxide topically and immiscibility between dimethyl
      sulfoxide and oleic acid. Further studies may be warranted.

PMID- 15253197
TI  - Vertical facial distraction in the treatment of arhinia.
AB  - Arhinia is a rare congenital malformation characterized by lack of the formation
      of external and internal nasal structures. Restricted midfacial growth is
      secondary to the loss of the midfacial growth centers. Staged reconstruction of
      the nasal passage and external nose is required. Vertical distraction
      osteogenesis is a beneficial step in the overall reconstructive program. This
      provides for additional bone and soft tissue for both improved aesthetic facial
      proportions and later surgical interventions.

PMID- 15253198
TI  - Surgical approach to the accessory nerve in the posterior triangle of the neck.

PMID- 15253199
TI  - Anterior conchal reconstruction using a posteroauricular pull-through
      transpositional flap.

PMID- 15253200
TI  - Extended lower trapezius island myocutaneous flap in the repair of postburn
      axillary contracture.

PMID- 15253201
TI  - Marking the position of the nipple-areola complex for mastopexy and breast
      reduction surgery.

PMID- 15253202
TI  - Embolization of a free flap nutrient artery to reduce late postoperative edema.

PMID- 15253203
TI  - Computer planning for breast reconstruction by tissue expansion: an update.

PMID- 15253204
TI  - Immediate breast reconstruction in two stages using textured, integrated-valve
      tissue expanders and breast implants.

PMID- 15253205
TI  - Breast reduction surgery and breast cancer risk: does reduction mammaplasty have
      a role in primary prevention strategies for women at high risk of breast cancer?
AB  - Prophylactic bilateral mastectomy has been demonstrated to reduce breast cancer
      incidence in women with a high inherited susceptibility to breast cancer. For the
      majority of high-risk women, however, bilateral prophylactic mastectomy is not an
      acceptable option for primary prevention of breast cancer. Several
      epidemiological follow-up studies have indicated that there may be a substantial
      reduction in breast cancer risk among women who have undergone breast reduction
      surgery. The authors reviewed the evidence from these studies, with emphasis on
      the problems inherent in interpreting the results of nonexperimental studies of
      elective medical procedures. Although such observational studies cannot
      demonstrate definitively that reduction mammaplasty reduces the risk of breast
      cancer, the evidence from these studies is sufficiently strong to warrant the
      evaluation of breast reduction surgery as an option for primary prevention in
      clinical studies of women at increased risk of breast cancer. The availability of
      a more acceptable surgical option for primary prevention of breast cancer could
      increase the number of women willing to choose risk reduction surgery and thus
      may result in an overall reduction in breast cancer mortality among high-risk
      women.

PMID- 15253206
TI  - Benjamin Franklin and plastic surgery.

PMID- 15253207
TI  - Fat extrusion and septal reset in patients with the tear trough triad: a critical
      appraisal.
AB  - Arcus marginalis release, fat extrusion, and septal reset were applied to 71
      selected patients with a constellation of orbital deformities the authors term a
      "tear trough triad." Of the initial 71 patients, 59 had complete follow-up
      records. Evaluated by means of a proportional topographic scale, 95 percent of
      patients achieved significant improvement. Equally important, no incidence of
      middle lamella contracture occurred in the entire series. The authors conclude
      that the procedure is safe and effective in selected patients.

PMID- 15253208
TI  - The role of the septal reset in creating a youthful eyelid-cheek complex in
      facial rejuvenation.
AB  - Resetting of the septum orbitale over the orbital rim, or "septal reset," is the
      latest step in achieving periorbital rejuvenation in composite rhytidectomy. The
      first significant step was the addition of orbicularis repositioning to
      conventional lateral vector deep plane rhytidectomy, followed by orbital fat
      preservation using the arcus marginalis release and fat transposition over the
      orbital rim. Those early procedures have been further refined to include the
      zygomaticus muscles with the orbicularis oculi in the composite flap, or
      zygorbicular cheek flap, and a septal reset. The septum orbitale reset has
      distinct advantages over transposition of orbital fat alone, as it creates a
      firmer undersurface for the lower eyelid. This maneuver will create a truly
      youthful lower eyelid-cheek complex, as the normal concave aging skeletonization
      of the periorbit is transformed to a convex contour of youth. The effectiveness
      of this operation can be demonstrated in most variations of human anatomy,
      whether congenital or iatrogenic, allowing the plastic surgeon to utilize the
      septal reset in virtually every patient undergoing and desiring a harmonious
      facial rejuvenation.

PMID- 15253209
TI  - Intraabdominal pressure after full abdominoplasty in obese multiparous patients.
AB  - This study measured intraabdominal pressure in morbidly obese and multiparous
      patients who underwent abdominoplasty with musculoaponeurotic plication. The
      purpose of this study was to evaluate any potential adverse effect on pulmonary
      function by virtue of pulmonary function tests and measurement of peak airway
      pressure. The study included 43 multiparous, morbidly obese women (mean body mass
      index, 35.8 kg/m2) with a mean age (+/- SD) of 38.6 +/- 7 years. All had full
      abdominoplasty and repair of the musculoaponeurotic system during the period from
      June of 1999 to May of 2002. Forty-three morbidly obese multiparous patients were
      seen over a period of 24 months. Their intraabdominal pressure was estimated by
      measuring the intravesical pressure before and after repair of severe diastases
      (divarication) of the rectus abdominis muscles with severely flaccid myofascial
      component before using a hydrometer connected to a Foley catheter both before and
      after repair. All patients had pulmonary function checked before and 2 months
      after the repair. The study confirmed that there are minimal changes on the
      intraabdominal pressure parameters compared with measurement before and after
      full abdominoplasty with plication of the rectus muscles, with minimal to
      negligible changes in the intrathoracic pressure. These changes are clinically
      and statistically significant (p < 0.0001). The study also recommended the safety
      of full abdominoplasty and repair of the musculoaponeurotic system in multiparous
      and morbidly obese patients. Furthermore, no statistically significant difference
      was found in pulmonary function parameters before and after surgery in patients
      with a history of bronchial asthma.

PMID- 15253210
TI  - Diced cartilage grafts in rhinoplasty surgery.
AB  - The use of diced cartilage grafts in rhinoplasty surgery was recently revived by
      Erol with the publication of his technique for "Turkish delight" grafts (i.e.,
      diced cartilage grafts wrapped in Surgicel). The present study details the
      authors' experience with 50 consecutive diced cartilage grafts used in three
      configurations during a prospective study of 50 primary and secondary aesthetic
      rhinoplasty procedures performed by the senior author (Daniel). Part I consists
      of 22 diced cartilage grafts wrapped in Surgicel and placed in the radix (n =
      14), radix/upper dorsum (n = 4), and full-length dorsum (n = 4). All grafts were
      performed adhering meticulously to Erol's technique without modification. This
      portion of the study was halted abruptly at 4 months because of the unexpected
      absorption and clinical failure of all diced cartilage grafts wrapped in
      Surgicel. Subsequently, five patients had revision surgery, and biopsy specimens
      were taken at the prior grafting site and analyzed histologically. After this
      clinical failure, part II of the study began, consisting of 20 patients who had
      diced cartilage grafts wrapped in fascia. The range of applications was
      comparable: radix (n = 12), radix/dorsum (n = 3), and full-length dorsum (n = 5).
      Because of our prior practice of overcorrecting by 20 percent with diced
      cartilage grafts wrapped in Surgicel, we had excessive amounts of material in six
      of our initial diced cartilage wrapped in fascia radix grafts, but no subsequent
      grafts. The overcorrections were easily reduced at 6 weeks to 11 months
      postoperatively using a pituitary rongeur under local anesthesia, and the
      material was sent for histologic analysis. Minimum 1-year follow-up of all 20
      cases has shown maintenance of the grafts without evidence of absorption. Part
      III of this study comprised eight patients who had diced cartilage grafts without
      a fascial covering placed throughout the nose, including on the sides of
      osseocartilaginous rib grafts to the dorsum. At 14 months, there was no evidence
      that any of these grafts had been absorbed. Histologic analysis of the biopsy
      specimens from the diced cartilage grafts wrapped in Surgicel showed evidence of
      fibrosis and lymphocytic infiltrates with small amounts of Surgicel visible on
      birefringent microscopy. Remnants of cartilage were present but were
      metabolically inactive on the basis of negative glial fibrillary acidic protein
      staining. Control specimens of fresh septal cartilage and banked septal cartilage
      were remarkably similar to each other and demonstrated normal cartilage
      architecture and cellular activity. The diced cartilage grafts wrapped in fascia
      showed coalescence of the diced cartilage into a single cartilage mass, with
      viable cartilage cells and normal metabolic activity on the basis of glial
      fibrillary acidic protein staining. All of the diced cartilage grafts wrapped in
      Surgicel absorbed and failed to correct the clinical problem for which they were
      performed. All of the diced cartilage grafts wrapped in fascia and pure diced
      cartilage grafts did correct the clinical deformities and appear to have survived
      completely. The diced cartilage grafts wrapped in fascia placed along the dorsum
      were distinctly palpable throughout the postoperative period, as was one prior
      case with a 6-year follow-up. The authors' clinical experience confirms the
      experimental studies of Yilmaz et al. that question the use of Surgicel for
      wrapping diced cartilage grafts in clinical rhinoplasty surgery.

PMID- 15253212
TI  - Customizing perioral enhancement to obtain ideal lip aesthetics: combining both
      lip voluming and reshaping procedures by means of an algorithmic approach.
AB  - Achieving predictable results with oral lip enhancement procedures is now
      possible. These procedures are categorized as either lip-reshaping or lip
      voluming techniques. By performing these techniques appropriately and
      simultaneously, the limitations of both are overcome and ideal lip aesthetics can
      be obtained in one operative setting. An algorithmic approach is presented to
      facilitate choice of techniques and when to combine them. This article also
      highlights the combination concept, discussing lip-reshaping procedures such as
      multiple mucosal advancements, modified paranasal lip lifts, and corner lip lifts
      performed in concert with voluming by means of fat transfer. However, the main
      focus of this article is on the fat transfer and simultaneous mucosal advancement
      (FATMA) procedure, one that has produced remarkable results in terms of
      permanency and aesthetic appeal. One-year to 7-year follow-up results are
      presented.

PMID- 15253211
TI  - Transpalpebral browpexy.
AB  - Transpalpebral browpexy could be performed as an adjuvant procedure to the upper
      blepharoplasty or as a separate procedure. It is done by separating
      interdigitalizing connections between the orbicularis and frontalis muscles,
      moving the orbicular part of the orbicularis muscle with overlying brow to the
      more cephalad position and again uniting both of these muscles with nonresorbable
      sutures in a new higher position. During the years 1990 to 1999, 55 patients (47
      women and eight men) were operated on with this technique, which was partially
      developed by the author. Additional time required to achieve transpalpebral brow
      stabilization during standard blepharoplasty was approximately 30 minutes. Forty
      three patients were followed, 38 of them for longer than 4 years. The elevation
      effect gradually decreased but persisted, with wide variations, between 1.5 and 7
      more years. At the last follow-up examination, 36 of 43 patients had maintained
      lateral brows in the same position as before operation and sometimes even higher,
      which was appreciated by the patients. Complications were very few and they were
      correctable. Transpalpebral browpexy proved to be a useful addition to
      blepharoplasty and can be used for the minor adjustments after an open coronal or
      endoscopic brow lift. Particular indications included patients with lateral brow
      ptosis and discrete forehead wrinkles and balding men.

PMID- 15253213
TI  - An anatomical method for re-siting the umbilicus.
AB  - The umbilicus is the only normal scar on the body and it is the most noticeable
      scar following abdominoplasty and TRAM or DIEP flap procedures. We describe a
      technique for resiting the umbilicus that attempts to recreate the anatomical
      structure by attaching the superficial fascia to the periumbilical skin to
      produce a fullness around the depression in which the umbilicus sits. This is
      aesthetically desirable and avoids the uncomfortable tethering of the umbilicus
      to the rectus sheath associated with other techniques.

PMID- 15253214
TI  - Anxiety disorders in plastic surgery.

PMID- 15253215
TI  - "Let's tell some bedtime stories".

PMID- 15253216
TI  - First signals.

PMID- 15253217
TI  - Transplantation tolerance and chimerism: what are they and do we need them?

PMID- 15253218
TI  - Earlobe aging process: elongation of the free caudal segment.

PMID- 15253219
TI  - Microgenia: an unusual complication of cesarean delivery.

PMID- 15253220
TI  - Poro carcinoma?

PMID- 15253221
TI  - Tracheostomy scar revision using acellular dermal matrix allograft.

PMID- 15253222
TI  - Endoscopic brow lift: a retrospective review of 628 consecutive cases over 5
      years.

PMID- 15253223
TI  - Vacuum-assisted closure therapy and oral anticoagulation therapy.

PMID- 15253224
TI  - A modified syringe suction drainage system.

PMID- 15253225
TI  - Dealing with a partially extruded suction drain.

PMID- 15253226
TI  - Microtia and pectoralis muscle agenesis.

PMID- 15253227
TI  - The use of botulinum toxin in treating a twitching TRAM flap.

PMID- 15253228
TI  - Dermal substitute (Integra) for open nasal wounds.

PMID- 15253229
TI  - Nipple-areola complex autonomization and delayed nipple-sparing subcutaneous
      mastectomy.

PMID- 15253230
TI  - De novo malignant eccrine poroma of the nose: a review of the midface as a
      location.

PMID- 15253232
TI  - Augmentation/mastopexy: "surgeon beware".

PMID- 15253231
TI  - Subclinical infection as a possible cause of significant breast capsules.

PMID- 15253233
TI  - Aesthetic reconstruction of the tuberous breast deformity.

PMID- 15253234
TI  - Laser treatment of congenital melanocytic nevi.

PMID- 15253235
TI  - Nonmelanoma of the skin and Mohs surgery.

PMID- 15253236
TI  - A lethal necrotizing fasciitis after human bite.

PMID- 15253237
TI  - Cerebral fat embolism induced by facial fat injection.

PMID- 15253238
TI  - The cut-and-slide conchal treatment.

PMID- 15253239
TI  - A great time for pioneers of superior extremity aesthetic surgery.

PMID- 15253240
TI  - Responsibilities of our journal editors and reviewers.

PMID- 15253241
TI  - More satisfaction in advanced baldness.

PMID- 15253242
TI  - Is the staging of melanoma the principal objective of its treatment?

PMID- 15253243
TI  - Postburn flexion contractions of the knee.

PMID- 15253244
TI  - The difference in estrogen receptor protein level between breast hypertrophy and
      micromastia.

PMID- 15253245
TI  - Intimal hyperplasia--still here after all these years!

PMID- 15253246
TI  - Perirenal fixation as an independent factor in aortic remodeling after
      endovascular aortic aneurysm repair.
AB  - The purpose of our study was to evaluate the influence of perirenal fixation of
      endovascular aortic grafts on the rate of endoleak and aortic sac remodeling.
      Retrospective analysis of all patients (pts.) after undergoing endovascular
      aortic aneurysm repair (EVAR) at our institution was performed. Pre- and
      postoperative aortic dimensions were obtained from CT scans and angiograms.
      Intraoperative angiograms were reviewed and patients grouped by the proximity of
      the graft to the lowest renal arteries: group I: flush with the lowest renal
      artery; group II: < or = 5 mm distal to lowest renal artery; and group III: >5 mm
      distal to lowest renal artery. Of the 96 grafts placed between 2000 and 2002, 44
      were AneuRx (Medtronic, Santa Rosa, CA) and 52 were Ancure (Guidant, Menlo Park,
      CA) devices. There were 39 pts. in group I, 42 in group II, and 11 in group III
      (data on 5 pts. were not obtained). At 6 months, the mean decrease in sac
      diameter for all groups was 0.42 +/- 0.08 cm (1: 0.56 +/- 0.11 cm; 11: 0.38 +/-
      0.11 cm; III: 0.6 +/- 0.15 cm). There was no significant difference between each
      group. When perirenal fixation (group I) was compared with nonperirenal fixation
      (groups II and III), there was a significant difference in sac shrinkage at 6
      months (p < 0.05, ANOVA). Group I had shorter necks and smaller aneurysms (2.2 +/
      0.1 cm and 5.3 +/- 0.1 cm) than those of groups II and III (2.7 +/- 0.1 cm and
      5.7 +/- 0.1 cm, p < 0.05, ANOVA). There was no difference in aortic neck diameter
      or in aortic neck diameter to graft ratio. When controlled for the variables
      studied (AAA diameter, length of neck, diameter of neck, diameter of neck to
      graft ratio, and any endoleak by 6 months), logistic regression analysis
      identified perirenal fixation as the only significant factor in aortic sac
      shrinkage of >0.4 cm by 6 months (odds ratio = 16, p < 0.01). With the same
      variables, a linear regression model also identified perirenal fixation as the
      only predictive factor in aortic shrinkage (regression coefficient = 0.46, p <
      0.05). The endoleak-free survival rate with perirenal fixation was 96 +/- 5% and
      without it was 80 +/- 7% (Kaplan Meier, p = 0.09, log rank). Perirenal placement
      of endovascular grafts is associated with a trend toward fewer endoleaks, and
      improved aortic sac shrinkage independent of aortic neck length, AAA diameter,
      diameter of neck, and endoleak. Failure to achieve perirenal placement of EVAG
      increased the likelihood of reduced or failed aortic sac shrinkage in this
      series.

PMID- 15253247
TI  - Is coil embolization of hypogastric artery necessary during endovascular
      treatment of aortoiliac aneurysms?
AB  - The aim of this study was to evaluate the safety and efficacy of stent graft
      coverage of hypogastric artery in the management of aortoiliac aneurysms. Between
      January 2000 and December 2002, 98 patients underwent endovascular repair of
      aortoiliac aneurysms (EVAR). Of these, 24 (24.5%) required occlusion of one
      hypogastric artery to facilitate the endovascular repair. Based on the method of
      hypogastric artery occlusion, patients were divided in to two groups. Group A
      (13/24 = 54%) underwent standard coil embolization followed by hypogastric artery
      orifice coverage whereas group B (11/24 = 46) underwent hypogastric artery
      orifice coverage without coil embolization. Post-EVAR computed tomographic
      angiography (CTA) was used to determine occurrence of endoleaks from the
      hypogastric artery orifice and patency of superior gluteal artery in both groups.
      These findings were further correlated with presence or absence of gluteal
      claudication. There was no difference in age (p < 0.38) or iliac aneurysm size (p
      < 0.3). In group A (13 patients), occlusion of superior gluteal artery was seen
      in 6 (46%). Four of six (66%) patients developed severe gluteal claudication.
      Patients in group A were likely to require more than one intervention (p <
      0.00036). No patients in group B developed occlusion of the superior gluteal
      artery (p < 0.04) or gluteal claudication (p < 0.046). No endoleaks were seen
      from the origins of hypogastric artery in either group. The follow-up period
      ranged from 2 to 35 months. Hypogastric artery orifice coverage without coil
      embolization effectively prevented retrograde endoleak without the occurrence of
      disabling gluteal claudication. Coil embolization of the hypogastric artery may
      be unnecessary during treatment of aortoiliac aneurysm.

PMID- 15253248
TI  - Inhibition of intimal hyperplasia by direct thrombin inhibitors in an animal vein
      bypass model.
AB  - Many functions of the coagulation system have nonthrombotic effects. The indirect
      thrombin inhibitor heparin has been previously shown to be effective in limiting
      intimal hyperplasia (IH). We sought to study the effect of thrombin on IH by
      using two direct thrombin inhibitors (DTIs), argatroban and lepirudin. Sprague
      Dawley rats underwent interposition vein grafting to the carotid artery. Vein
      grafts were treated with either saline (n = 6) or one of the two DTIs (n = 6 for
      both). At 30 days, the rats were sacrificed and vessels were perfusion fixed.
      Sections of the proximal carotid artery, graft, and both anastomoses were stained
      with both hematoxlyin/eosin and von Gieson's elastin stain. Sections were
      examined and compared for luminal area and intima-to-media (IM) ratio. The
      vessels treated with DTIs had less (p < 0.05) IH (IM ratio for proximal
      anastomosis: control 1.036 +/- 0.857, lepirudin 0.373 +/- 0.21, argatroban 0.182
      +/- 0.118) and better lumen preservation than the control vessels (lumen area of
      proximal anastomosis: control 1.69 +/- 0.9, lepirudin 2.45 +/- 0.74, argatroban
      2.81 +/- 0.78). There were no thromboses in the DTI-treated vessels. Dilatation
      of the graft segment was noted in the argatroban group. Thus, DTIs are effective
      at reducing IH in a small-animal model, suggesting that inhibition of thrombin
      has a protective role in IH. In addition, a difference of action between DTIs is
      suggested by the dilatation seen only in the argatroban-treated graft sections.

PMID- 15253249
TI  - Impact of carotid artery angioplasty and stenting on management of recurrent
      carotid artery stenosis.
AB  - Citing the higher perioperative risk of redo carotid surgery, balloon angioplasty
      and stenting of the carotid artery (CAS) has been advocated for recurrent carotid
      stenosis (RCS). To examine the impact of CAS on the management and outcome of
      recurrent stenosis, a retrospective review of a prospectively compiled database
      was performed. From a registry of patients treated for carotid disease, 105
      procedures were performed from 1992 to 2002 for RCS. For comparison, two study
      groups were examined. Time I consisted of 77 reoperations performed through 1998,
      before CAS was introduced at our institution. Time II included 12 reoperations
      and 16 CAS procedures performed for RCS from 1999 through 2002. Using
      perioperative stroke as a measure of outcome, the results for time II were poorer
      than for time I (7.2% vs. 5.2%, p = NS). Overall, the risk of perioperative
      stroke was the same for reoperation (5/89) and CAS (1/16) (5.6% vs. 6.3%, p =
      NS). Although not statistically significant, there was a trend toward a higher
      risk of perioperative stroke for patients treated with reoperation during the
      latter time period (8.3% vs. 5.2%, p = NS). This probably relates to the finding
      that during time II, CAS was most likely to be used in asymptomatic patients
      (68.6% vs. 41.7%, p = NS) with early (<3 years) RCS (87.5% vs. 41.7%, p= 0.01).
      No patient with asymptomatic, early RCS had a perioperative stroke with either
      surgery or CAS (0/35 cases, 0%). The presence of preoperative neurologic symptoms
      was significantly predictive of a perioperative stroke among all procedures
      performed for RCS (13.6% vs. 0%, p = 0.004). Contrary to suggestions that CAS
      might improve the management of RCS, a review of our data shows the overall risk
      of periprocedural stroke to be no better since CAS has become available. The bias
      for using CAS for asymptomatic myointimal hyperplastic lesions, and reoperation
      for frequently symptomatic late recurrent atherosclerotic disease, makes direct
      comparisons of the two techniques for treating RCS difficult. It is expected that
      the overall risk for redo carotid surgery will increase, as fewer low-risk
      patients will be receiving open procedures. However, the increased risk among
      symptomatic patients undergoing reoperation suggests that endovascular techniques
      should be investigated among this group of cases as well.

PMID- 15253250
TI  - Management trends and early mortality rates for acute type B aortic dissection: a
      10-year single-institution experience.
AB  - This study was undertaken to assess trends in management over time and to
      determine predictors of early mortality for acute type B aortic dissection. Fifty
      three consecutive patients with acute type B aortic dissection over a 10-year
      period were reviewed. Baseline demographics as well as in-hospital data regarding
      symptoms, type of initial management, surgical indications, type of surgical
      intervention, and early mortality rates were collected. Independent predictors of
      early mortality were determined by logistic regression. Forty-one of 53 (77.4%)
      patients were initially managed medically with a total of 26 (49.1%) ultimately
      undergoing surgical repair during hospitalization. Crude early mortality was
      30.8% in the surgical group vs. 14.8% in the medical group (p = 0.20).
      Improvements in early mortality were observed over time for surgery (58.3%, first
      half vs. 7.1%, second half; p = 0.019) and medical therapy (21.4%, first half vs.
      7.7%, second half; p = 0.64). Early mortality was 50% in 16 patients having open
      aortic surgery vs. 0% in 10 patients undergoing endovascular stent graft repair
      (p < 0.005). Independent predictors of early mortality included only renal
      dysfunction (odds ratio [OR] 7.39), aortic rupture (OR 8.72), and date of
      admission during the study period (OR 0.712). Despite improvements over time in
      early mortality that appear associated with the increasing use of endovascular
      stent grafts, patient-specific factors are still the most important independent
      predictors of early mortality in acute type B aortic dissection.

PMID- 15253251
TI  - Impaired hyperemic response is predictive of early access failure.
AB  - The aim of this study was to demonstrate that hyperemic response is a predictor
      of access failure. We conducted a review of a prospective database of dialysis
      access patients with preoperative hyperemia studies from June 1998 to August
      2002. These consisted of bilateral brachial artery pressures followed by flow
      velocity measurements of the brachial artery and radial artery at rest and after
      3 min of arm ischemia. Measurements were taken by using a cuff placed above the
      antecubital fossa and inflated to 20 mmHg above systolic pressure. There were no
      differences recorded in brachial artery pressures for the bilateral studies.
      Hyperemic response was entered into a stepwise Cox regression to determine its
      effect on access failure. Access failure was defined as failure to mature or
      thrombosis. Accesses were placed according to Dialysis Outcome Quality Intiatives
      (DOQI) guidelines. Kaplan-Meier survival analysis was performed. Log-rank testing
      was used to compare patency results. Censored end points were death, renal
      transplant, and access survival to the end of the study period. Fistulas that
      failed to mature were considered failures at 3 months. Arteries with a <5 cm/sec
      increase in peak systolic velocity were defined as nonresponders. The 59 arteries
      used for dialysis access were divided into two groups on the basis of their
      hyperemic response in cm/sec. The nonresponders were compared with the remainder
      of accesses performed. Accesses based on arteries with absent or minimal
      hyperemic response had significantly lower (p < 0.0005) secondary patencies by
      Kaplan-Meier analysis. Upon further stratification into radial and brachial
      arteries, the significant difference in secondary patency remained for radial
      artery--based accesses (p = 0.024) and approached statistical significance for
      brachial artery--based accesses (p = 0.057). A significant difference was not
      seen in primary patencies, indicating that accesses based on arteries with an
      acceptable hyperemic response are more likely to be salvaged by revisions. A
      nonresponsive radial artery was not a significant predictor of a nonresponsive
      brachial artery in the same extremity by binary logistic regression (p = 0.111),
      and a nonresponsive artery was not a significant predictor of nonresponsiveness
      in the corresponding artery in the contralateral extremity (p = 0.137). Cox
      regression analysis revealed that the hyperemic response is a significant
      predictor of failure to mature or thrombosis. Hyperemic testing is a useful means
      of evaluating adequate arterial inflow for dialysis access. Reduced or absent
      hyperemic response is an independent predictor of access failure.

PMID- 15253252
TI  - Dose-dependent inhibition of myointimal hyperplasia by orally administered
      rapamycin.
AB  - Myointimal hyperplasia (MIH) after vascular intervention is a major problem.
      Recent reports describing elimination of within-stent restenosis by means of
      rapamycin-eluting stents prompted us to examine the effect of systemic oral
      rapamycin on MIH induced by arterial trauma. We studied the effect of oral
      rapamycin on MIH after rabbit aorta balloon injury. Thirty-five New Zealand white
      rabbits (2.5-3 kg) had aortic injury and were given either no rapamycin
      (control), 0.1 (low dose) rapamycin mg/kg/day, or 0.4 mg/kg/day (high dose).
      Rapamycin was started 1 week before injury and continued for 3 (4 weeks total) or
      6 weeks (7 weeks total) post-injury. Sections were analyzed to measure aortic
      intima/media area ratios (I:M) at either 3 or 6 weeks. At 3 weeks, the I:M (mean
      +/- SD) for controls was 0.53 +/- 0.1; for low dose, 0.17 +/- 0.13; and for high
      dose, 0.24 +/- 0.07 (p < 0.001 vs. control). At 6 weeks, the I:M for controls was
      0.52 +/- 0.12; for low dose-4 weeks, 0.29 +/- 0.15; low dose-7 weeks, 0.33 +/-
      0.07; and high dose-4 weeks, 0.47 +/- 0.16. At 6 weeks only the difference
      between the low dose-4 weeks and control I:M ratios was significant (p = 0.018).
      The results confirm earlier studies showing that systemic rapamycin inhibits MIH
      after arterial injury when drug therapy is started before injury. Therapy for 3
      or 6 weeks after injury yields similar inhibition, indicating that exposure to
      the drug early in the response to injury is more important than prolonged
      exposure. We observed a paradoxical relation between dose and degree of MIH
      inhibition, with the low dose being more effective than the high dose at both
      time intervals studied. Overall, the results suggest that oral rapamycin therapy
      might be a useful adjunct to clinical interventions at risk for development of
      MIH.

PMID- 15253253
TI  - The proximal landing zone in endovascular repair of the thoracic aorta.
AB  - In this study we evaluated the relationship between the site of the proximal
      landing zone during endovascular repair of thoracic aortic pathology and
      treatment outcomes. We reviewed all cases of endovascular repair of thoracic
      aortic lesions at our institution in the past 42 months. Thirty-seven Talent
      thoracic endografts were used to treat 20 thoracic aneurysms, 8 intramural
      hematomas, 6 aortic dissections, and 3 post-traumatic aneurysms. The proximal
      edge of the covered endograft was situated proximal to the left common carotid
      artery (zone 1) in 3 patients, between the left common carotid and subclavian
      arteries (zone 2) in 4 patients, <2 cm distal to the left subclavian artery (zone
      3) in 9 patients, and >2 cm distal to the left subclavian (zone 4) in 21
      patients. Five patients had extraanatomic bypass to revascularize one or more
      covered aortic branches. For zones 1, 2, 3, and 4 the endoleak rates were 100%,
      0%, 11%, and 0%, respectively; the secondary procedure rates were 33%, 0%, 11%,
      and 5% respectively; and the treatment failure rates were 67%, 0%, 11%, and 0%,
      respectively (p < 0.05, for endoleak rates, using Fisher's exact test to compare
      zone 1 to zones 2, 3, and 4 individually, and as a group). All three endovascular
      failures were due to proximal type 1 endoleaks. In conclusion, despite the use of
      great-vessel ligation and extraanatomic bypass to extend the proximal landing
      zone into the aortic arch, we have been unable to reliably exclude thoracic
      aortic pathology through use of endografts when the proximal landing zone is
      proximal to the left common carotid artery.

PMID- 15253254
TI  - Surgical thrombectomy and transluminal balloon angioplasty for failed above-knee
      femoropopliteal polytetrafluoroethylene bypass grafts.
AB  - Endovascular therapy offers an alternative to redo bypass or surgical graft
      revision for failed above-knee femoropopliteal PTFE bypass grafts. We evaluated
      the outcome of surgical thrombectomy and balloon angioplasty for the treatment of
      thrombosed bypass grafts. Thirty selected patients with thrombosed above-knee
      femoropopliteal PTFE bypass grafts were treated. Under local anesthesia, a
      surgical thrombectomy followed by bypass graft angiography and balloon
      angioplasty of perianastomotic stenoses was performed. Stents were used
      selectively for suboptimal angioplasty results. Patients underwent duplex
      scanning of the bypass graft postoperatively and at 6-month intervals. Life-table
      analysis and log-rank (Mantel-Cox) comparisons were performed. Patients were
      categorized into two groups on the basis of time elapsed from initial bypass
      graft construction to graft failure. Group 1 included 21 patients with a mean
      time to graft failure of 10 months (range, 0-20). Surgical thrombectomy was
      successful in 20 grafts (95%) and 17 patients had a stent placed after
      angioplasty. Rethrombosis occurred within 30 days in seven grafts (33%) in group
      1 and major amputations were performed in six patients (28%). Group 2 included
      nine patients with a mean time to initial bypass graft failure of 48 months
      (range, 29-96). All patients in group 2 had a successful surgical thrombectomy
      and all received a stent. None of the grafts treated in group 2 reoccluded within
      30 days of intervention and one patient (11%) went on to require a major
      amputation. By life-table analysis, the 6- and 12-month patency for group 1 was
      15.3% and 5.1%, compared to 58.3% and 38.9% for group 2 (p = 0.027). Surgical
      thrombectomy along with balloon angioplasty has an unacceptably high rate of
      failure and limb loss in patients treated for early (<2 years) femoropopliteal
      PTFE bypass graft thrombosis. Surgical graft revision or redo bypass is
      recommended to achieve successful revascularization in these patients. Treatment
      with surgical thrombectomy and balloon angioplasty achieves significantly greater
      short-term patency results in patients with late (>2 years) bypass graft failure
      and may be a reasonable alternative for patients who cannot tolerate reoperation
      or lack autogenous conduit.

PMID- 15253255
TI  - Surveillance venous duplex is not clinically useful after total joint
      arthroplasty when effective deep venous thrombosis prophylaxis is used.
AB  - The early detection of deep venous thrombosis (DVT) and treatment with systemic
      anticoagulation to prevent pulmonary embolism (PE) are essential in the
      management of patients undergoing total joint arthroplasty (TJA). However,
      improvements in prophylactic measures have significantly decreased the occurrence
      of DVT in these patients. The purpose of this study was to determine whether
      routine postoperative duplex surveillance for DVT remains clinically useful. The
      medical records of all patients undergoing total knee or total hip arthroplasty
      between October 1997 and January 2002 at a University Hospital and its Veterans
      Affairs (VA) affiliate were reviewed. The type of operation and occurrence of
      complications (e.g., DVT, PE, and hemorrhage) were noted. All patients were
      treated postoperatively with both enoxaparin 30 mg b.i.d. and bilateral lower
      extremity sequential compression devices (SCDs). A venous duplex scan was
      performed prior to discharge. Three hundred ninety-eight patients underwent 441
      TJAs for 149 hips and 292 knees. The average age was 65 years (range, 23-95).
      Venous duplex scans were performed within 1 week (median, 4 days) of operation.
      Initial inpatient scans revealed acute, ipsilateral DVT in five patients (1.3%).
      Three patients experienced documented PE-one as an inpatient and two after
      hospital discharge; both outpatients had negative inhospital duplex scans. One of
      the 398 patients did not have a duplex scan as an inpatient and returned 6 weeks
      later with a popliteal DVT. Complications included one upper gastrointestinal
      hemorrhage, and one patient died postoperatively of unknown causes. These data
      demonstrate that routine postoperative venous duplex scans rarely found DVT (5 of
      398 patients) after TJA when effective prophylaxis was used. Furthermore,
      surveillance scanning did not enable reliable prediction of PE. Therefore, we
      conclude that postoperative inpatient surveillance duplex scans for DVT provide
      very minimal benefit and that a routine screening program is not clinically
      useful for patients managed with effective DVT prophylaxis.

PMID- 15253256
TI  - Multicenter randomized prospective trial comparing a pre-cuffed
      polytetrafluoroethylene graft to a vein cuffed polytetrafluoroethylene graft for
      infragenicular arterial bypass.
AB  - Poor patency of synthetic grafts for infragenicular revascularization has led to
      use of distal vein patches or cuffs. The aim of this study was to compare the
      distally widened Distaflo PTFE graft, which mimics a vein cuff, with a PTFE graft
      with distal vein modification. In this prospective, randomized, multicenter trial
      we compared use of a precuffed PTFE graft wit that of PTFE grafts with distal
      vein modification for infragenicular revascularization in patients with critical
      limb ischemia without saphenous vein. Study end points were primary and secondary
      patency and limb salvage rates at 2 years. From January 28,1999 to November 1,
      2000, 104 patients were enrolled in 10 North American centers. Thirteen were
      excluded for protocol violation. Ninety-one bypasses were performed in 89
      patients with a mean age of 73 years (range 47-90). By randomization, 47 bypasses
      were done with the precuffed graft and 44 with PTFE graft with vein cuff. Both
      groups were comparable for comorbidities and operative variables, except for a
      higher incidence of acute ischemia in the precuffed group (19% vs. 4.5%, p =
      0.03). Bypass was a redo procedure in 53% and was performed at the infrapopliteal
      vessels in 79%. Operative mortality was 2.2% (2/91). Mean follow-up was 14 months
      (range 1-30). At 1 and 2 years, primary patency was 52% and 49% for the precuffed
      group and 62% and 44% for the vein cuffed group, respectively (p = 0.53). At 1
      year and 2 years, the limb salvage rate was 72% and 65% for the precuffed group
      and 75% and 62% in the vein cuffed group (p = 0.88). Although numbers are small
      and follow-up short, this midterm analysis shows similar results for the Distaflo
      precuffed grafts and PTFE grafts with vein cuff. A precuffed graft is a
      reasonable alternative conduit for infragenicular reconstruction in the absence
      of saphenous vein and provides favorable limb salvage.

PMID- 15253257
TI  - Postoperative changes in duplex ultrasound velocity characteristics in the
      nonmobilized right internal mammary artery in patients with left internal mammary
      artery bypass grafting.
AB  - The internal mammary artery (IMA) is the conduit of choice in coronary
      revascularization because of its long-term patency. We analyzed the effect of
      left internal mammary artery (LIMA) harvesting on sternal perfusion. Diameters
      and velocity parameters of the nonmobilized right internal mammary artery (RIMA)
      were noninvasively analyzed with duplex ultrasound in 41 patients with LIMA
      myocardial revascularization pre- (2.6 +/- 5 days) and postoperatively (4.9 +/-
      3.9 months). Data of 41 patients were analyzed; 38 patients underwent all
      examinations with adequate supraclavicular signals. The proximal RIMA diameter
      and all velocity parameters increased significantly at follow-up (3.1 +/- 0.6 vs.
      3.2 +/- 0.5 mm, p = 0.03; diastolic peak velocity [DPV] 15 +/- 7 vs. 27 +/- 9
      cm/sec, p < 0.0001; systolic peak velocity [SPV] 90 +/- 24 vs. 105 +/- 29 cm/sec,
      p < 0.02). This was more pronounced for the diastolic parameters and for all
      parameters in the proximal part of the RIMA than in the distal part (DPV 11.9 +/-
      10.1 vs. 9.5 +/- 10.2 cm/sec, p = NS; SPV 14.9 +/- 33.9 vs. 7.4 +/- 26.0 cm/sec,
      p = NS). With longer time intervals of follow-up the increase in all diastolic
      velocity parameters became less pronounced. As demonstrated in the RIMA velocity
      parameters, patients with skeletonized LIMA grafts (n = 4) had significantly more
      flow, suggesting hyperemic flow, than patients with pedicled LIMA grafts (n =
      34). Only in diastolic velocity integral (DVI) and systolic/diastolic velocity
      ratio (SDVRA) were there significant differences between diabetics (n = 9) and
      nondiabetics (n = 29) and only in DVI between female, (n = 8) and male (n = 30)
      patients. This study indicates that duplex ultrasound is a useful tool for
      noninvasive RIMA follow-up in LIMA myocardial revascularization.

PMID- 15253258
TI  - Has the emergence of endovascular treatment for aneurysmal and occlusive aortic
      disease increased the complexity and difficulty of open aortic operations?
AB  - With the emergence of endovascular surgery, there is a perception that open
      aortic procedures for aneurysmal and occlusive disease have become more
      difficult. To test this hypothesis, two consecutive groups of patients undergoing
      open aortic surgery for aneurysmal (AAA) and occlusive (AIOD) disease before and
      after the establishment of an endovascular program (EP) were analyzed. The pre-EP
      patient group (January 1996 through December 1997) consisted of 112 patients (52
      with AAA, 60 with AIOD) and the post-EP patient group (January 2000 through
      December 2001) consisted of 142 patients (72 with AAA, 70 with AIOD). The pre-EP
      AAA group was compared with the post-EP AAA group and the pre-EP AIOD group was
      compared with the post-EP AIOD group. Factors analyzed included patient
      demographics, comorbidities, and operative outcomes. Statistical comparisons were
      carried out using Fisher's exact test for proportions and the Wilcoxon rank-sum
      test for medians. There were no statistical differences in patient demographics
      between the pre-EP and post-EP groups, regardless of procedure. When considering
      AAA repair, there was a higher rate of hypertension and hypercholesterolemia in
      the pre-EP group and a higher number of total comorbidities per patient in the
      post-EP group. There was also an increased incidence of perioperative blood
      transfusion in the post-EP group. When considering open procedures for AIOD,
      there was an increased rate of hypertension and history of previous abdominal
      operation in the post-EP group. There also was an increased incidence of
      perioperative blood transfusion. Other than these factors, there were no
      statistically significant differences between the pre- and post-EP groups with
      regard to mortality, complication rate, length of procedure, blood loss, length
      of ICU stay, or length of hospital stay for either the aneurysmal patients or the
      occlusive disease patients. With only minor exception, endovascular surgery has
      not appreciably increased the complexity of open aortic operations performed for
      either AAA or AIOD.

PMID- 15253259
TI  - Predictors of early discharge following open abdominal aortic aneurysm repair.
AB  - Patients undergoing endovascular abdominal aortic aneurysm (AAA) repair have
      lower perioperative morbidity and leave the hospital earlier than patients
      undergoing open repair. However, potential complications require continuous
      surveillance of endografts and there are few data regarding their long-term fate.
      If an open operation were well tolerated, this might be a preferable alternative.
      The purpose of this study was to identify patients with lower morbidity and
      shorter hospital stay following open AAA repair and to analyze factors that might
      point to open repair as the preferred approach. We performed a retrospective
      review of all patients who underwent AAA repair between 1995 and 2000 at our
      institution. All patients with ruptured aneurysms and those that required renal,
      celiac, or superior mesenteric reconstructions during the AAA repair were
      excluded. Patient demographics, preoperative comorbid conditions, intraoperative
      data, and postoperative complications were analyzed in detail. A total of 115
      patients fulfilled the inclusion criteria. There was only one perioperative death
      (0.9%). The mean hospital stay was 8.1 days. A history of chronic obstructive
      pulmonary disease (COPD) and longer operative time were independent factors
      associated with prolonged hospital stay. Forty-one patients (35.6%) left the
      hospital in 5 or less days. Compared to the group with hospital stay >5 days,
      these patients had a lower incidence of COPD (7.3% vs. 25.7%, p < 0.05) and
      smaller-size AAAs (5.6 vs. 6.4 cm, p < 0.0001), and were more often operated on
      via a retroperitoneal approach (61% vs. 40.5%, p < 0.05). Their time in the
      operating room was less (3.5 vs. 4.5 hr, p < 0.0001), and they had less estimated
      blood loss (750 vs. 1500 cc, p < 0.001) and fewer transfusions (0.95 vs. 2.45
      units, p < 0.0001). Patients without COPD and smaller AAAs that can be repaired
      via a retroperitoneal approach have a lower incidence of perioperative
      complications and a shorter hospital stay following open AAA repair. Until long
      term results for endografts are available, our data suggest that these patients
      are well served with an open repair.

PMID- 15253260
TI  - Saphenous vein loop to femoral artery arteriovenous fistula: a practical
      alternative.
AB  - Secondary to central venous stenosis or thrombosis, alternate sites for permanent
      hemodialysis need to be explored. The authors' experience with the greater
      saphenous vein to common femoral artery loop arteriovenous fistula (GSV-CFA AVF)
      is presented. A retrospective review was performed of 4 women and 3 men with a
      mean age of 52.7 (range, 44-68) years. The mean number of prior access procedures
      was 3.85 (range, 1-5). Duplex ultrasound showed the greater saphenous vein (GSV)
      to be at least 3 mm in diameter. Perioperatively, no acute occlusion or
      significant steal syndrome developed. Groin wound complications (57.1%) resolved
      with local wound care and selectively antibiotic administration. Six patients
      developed mild to moderate edema, which required knee-high compression stockings.
      The mean follow-up was 15 (range, 9-24) months. Mean primary patency was 7
      months, primary assisted patency was 15 months, and secondary patency was 16
      months. The fistula was functional for hemodialysis in 71.4% (5/7). All patients
      developed stenoses within the GSV loop, with a mean of 3.0 balloon angioplasties
      per fistula. Three secondary surgical procedures were performed (two
      pseudoaneurysm repairs, one vein patch angioplasty). The GSV did not increase
      significantly in diameter. Use of a GSV-CFA AVF for dialysis access has
      acceptable results for alternate-site hemodialysis access. Secondary procedures
      were common. Factors recognized to be important for success were an adequate
      sized GSV preoperatively, positioning of the GSV loop, and patient body habitus.

PMID- 15253261
TI  - Endovascular management of iliac vein occlusive disease.
AB  - Iliac vein occlusive disease presents with either acute or chronic symptoms, both
      of which can be managed with endovascular techniques. This report summarizes our
      experience in a small cohort of patients undergoing percutaneous treatment of
      iliac vein occlusive disease. Six women and one man with occlusive lesions in the
      iliac veins are included in this report. All patients reported leg pain and
      swelling, involving the right leg in one and the left leg in six. Symptoms were
      acute in one patient and chronic in six. Two patients presented with a chronic
      stasis ulcer. All patients with chronic symptoms were treated with self-expanding
      stents deployed across the occlusive lesion. The patient with acute symptoms was
      treated successfully with thrombolysis, which uncovered a fixed stenosis that was
      then stented. Post-procedure follow-up with duplex scanning was used for vein
      patency. No significant complications occurred. All patients reported symptomatic
      improvement, with four having complete resolution. Duplex scanning showed all
      treated venous segments to be patent at a mean of 12 months. Recanalization of
      obstructed iliac vein segments can be performed successfully and leads to
      improvement in pain and edema in the affected limb. Midterm patency rates are
      excellent.

PMID- 15253262
TI  - Great saphenous vein leiomyosarcoma: a rare malignant tumor of the extremity--two
      case reports.
AB  - Peripheral vascular leiomyosarcomas are rare. Two cases of intramural
      leiomyosarcomas of the great saphenous vein are described. The first case is
      considered a high-grade sarcoma, based on the high mitotic index on histologic
      study. The second case presents only infrequent mitoses on light microscopy.
      Immunohistochemical analysis for factor VIII helped to establish the diagnosis.
      Characteristics of the tumor and differential diagnosis are discussed. Treatment
      consisted of wide local excision. Radiotherapy and chemotherapy were given to the
      patient with high-grade tumor.

PMID- 15253263
TI  - A case of warfarin skin necrosis despite enoxaparin anticoagulation in a patient
      with protein S deficiency.
AB  - Warfarin-induced skin necrosis is a rare complication associated with the use of
      oral anticoagulants. Most patients develop this at the initiation of therapy,
      often while still receiving intravenous unfractionated heparin (UFH). Recently,
      low-molecular-weight heparins (LMWHs) have gained wider use, providing an option
      for outpatient treatment of deep-vein thrombosis. The treatment protocols are
      similar to UFH, including the early initiation of oral anticoagulation with
      warfarin. A Medline search failed to reveal any cases of warfarin-induced skin
      necrosis while using a LMWH. We present a patient with protein S deficiency who
      developed warfarin skin necrosis despite appropriate anticoagulation with
      enoxaparin, and review the chemical and clinical difference between UFH and LMWH.

PMID- 15253264
TI  - Lemierre's syndrome associated with septic pulmonary embolism: a case report.
AB  - An 18-year-old female patient suffering from a painful right-sided neck mass was
      admitted to our emergency service. Computed tomography of the neck revealed
      thrombosis of the right internal jugular vein. Computed tomography of the chest
      indicated septic pulmonary emboli in both lungs. Blood and oropharyngeal cultures
      showed proteus that was sensitive to cefepime and amicasin. Chemotherapy was
      administered for 12 days, however, her complaints continued with fulminant
      progression. An urgent decompression and excessive debridement were performed.
      Although Lemierre syndrome is a well-known cause of internal jugular vein
      thrombosis, association with proteus culture is very rare.

PMID- 15253265
TI  - Transoesophageal echocardiogram identifying the source of endoleak after combined
      open/endovascular repair of a type 3 thoracoabdominal aortic aneurysm.
AB  - Open repair of thoracic aortic aneurysms is associated with significant morbidity
      and mortality. The introduction of endovascular repair has reduced both the
      morbidity and mortality. However, endovascular stent repair can be complicated by
      endoleaks. We report here the successful treatment of a type 2 endoleak following
      endovascular repair of a thoracoabdominal aortic aneurysm, using transesophageal
      echocardiography to assist in the localization of the thoracic endoleak.

PMID- 15253266
TI  - Superior mesenteric artery syndrome: an uncommon complication of abdominal aortic
      aneurysm repair.
AB  - The superior mesenteric artery syndrome (SMAS) is an uncommon finding, especially
      when occurring after open abdominal aortic aneurysm (AAA) repair. Very few cases
      have been previously reported in the literature. The underlying anatomic
      mechanism as well as a better way to manage this complication remains
      controversial. We report a case of well-documented duodenum obstruction occurring
      after an elective, uneventful open AAA repair in an 83-year-old white male. The
      patient was initially discharged from hospital on the fifth postoperative (PO)
      day but was readmitted on the seventh PO day with suspicion of intestinal
      obstruction caused either by adhesions or extrinsic pressure by a retroperitoneal
      hematoma. A laparotomy carried out on the 10th PO day was unremarkable and the
      patient continued vomiting until a left lateral decubitus positioning was
      assumed. The patient was discharged home on the 19th PO day and has remained well
      since.

PMID- 15253267
TI  - Pressure-controlled vascular clamp: a novel device for atraumatic vessel
      occlusion.
AB  - Morphological vessel injury after clamping has been an important problem in
      vascular surgery. Although various techniques have been employed to occlude a
      vessel during a surgical procedure, a complete, atraumatic occlusion method has
      not yet been developed. In the present study, we describe use of a novel pressure
      controlled and balloon-jawed vessel clamp to provide atraumatic vessel occlusion.
      We compared its traumatic effect on femoral arteries with that resulting from use
      of a conventional De Bakey vascular clamp in a canine model. During surgical
      application, our clamp provided complete vessel occlusion with no oozing in
      distal arteriotomy. On histological examination of the clamped vessel segments,
      we observed no destruction of the vessel wall, compared to widespread injury of
      the De Bakey vascular clamp. Despite some difficulties in application, we think
      this technique could be a promising method for vascular procedures.

PMID- 15253269
TI  - Are we doing enough to protect mice from infectious agents?

PMID- 15253268
TI  - Transcervical carotid artery angioplasty and stenting with carotid flow reversal:
      surgical technique.
AB  - We have performed this technique in 40 patients with carotid artery stenosis. No
      deaths or strokes have occured. During the initial experience, one patient in
      whom flow reversal was not properly established sutained an hemispheric transient
      ischemic attack. Transcervical carotid artery balloon dilatation and stenting is
      feasible and safe. It establishes reliable cerebral protection before the carotid
      lesion is instrumented by reversing flow in the internal and external carotid
      arteries. It can be done under local anesthesia, and it avoids the potential
      limitations, complications, and additional cost of the transfemoral approach with
      protection devices.

PMID- 15253270
TI  - Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route
      of administration, pitfalls, and insulin treatment.
AB  - Uncertainties have existed regarding the systematic induction and management of
      drug-induced diabetes mellitus (DM). Issues have included the optimal route of
      administration of the drug, methods of reducing drug toxicosis and mortality, how
      to induce type-1 versus type-2 DM, and how to manage labile DM in rats. In
      attempting to induce type-1 DM in Sprague-Dawley rats, we classified
      hyperglycemic animals as having type-1 DM only if their post-treatment blood
      ketone concentration was high. We found that multiple doses of alloxan led to
      significantly higher mortality than did a single dose. A single high dose (200
      mg/kg of body weight given intraperitoneally) was the best treatment and led to
      70% incidence of type-1 DM and only 10% mortality. In contrast, intravenous
      administration of similar doses was toxic. Assiduous management of alloxan
      induced DM is crucial to avoid severe hypoglycemia from massive insulin release
      and to avoid diabetic ketoacidosis. Frequent glucose monitoring and appropriate
      administration of carbohydrate and fluids is necessary during this stage. For
      long-term management, daily administration of long-acting insulin (glargine)
      appears to be safe and effective. Rapid-acting insulins reduce glucose
      concentration rapidly, and must be used with caution. If specific precautions are
      observed, intraperitoneal administration of high-dose alloxan to laboratory rats
      leads to a condition that closely resembles human type-1 DM.

PMID- 15253271
TI  - Mouse models of human cancers (part 3).

PMID- 15253272
TI  - Subsets of T cells in healthy rhesus macaques (Macaca mulatta) infected with
      simian T-lymphotropic virus type 1.
AB  - Simian T-lymphotropic virus type 1 (STLV-1) is a C-type retrovirus of nonhuman
      primates that is genetically and antigenically related to human T-lymphotropic
      virus type 1 (HTLV-1). Infection with STLV-1 has been reported in many species of
      Old World monkeys and apes, including rhesus macaques (Macaca mulatta). Similar
      to HTLV infection in humans, STLV infection has been associated with T-cell
      lymphoproliferative disease or lymphoma in a small proportion of infected
      animals, predominantly African species. There are conflicting reports of T-cell
      subset alterations in healthy HTLV-1 carriers. To the authors' knowledge,
      analysis of T-cell subsets in healthy STLV-1 carrier rhesus macaques has not been
      reported. Subsets of T cells in peripheral blood from healthy, STLV-1
      seropositive rhesus macaques (n = 17) and seronegative controls matched for age
      and sex (n = 17) were determined by use of fluorescence-activated cell sorter
      analysis. Parameters measured included CD3, CD4, CD8, CD25, CD28, CD38, and HLA
      DR cell sets. Significant differences in T-cell subsets or hematologic parameters
      were not observed between healthy STLV-seropositive and seronegative groups.

PMID- 15253273
TI  - Dense cataract and microphthalmia--new spontaneous mutation in BALB/c mice.
AB  - We describe a new spontaneous mutation in BALB/c mice that causes abnormal
      phenotype, such as congenital cataract and microphthalmia. This abnormality was
      found to be inheritable because offspring with the same abnormality were produced
      by backcrossing the abnormal male to its normal female parent. Results of various
      crosses made to determine the mode of inheritance indicated that this abnormality
      is attributable to mutation of an autosomal recessive gene. Slit lamp examination
      of the mutant eyes revealed total lenticular opacity, disturbed typical iris
      pattern, and abnormal pupillary muscle development. Histologic changes in mutant
      eyes between gestation day 13 and postnatal day 1 indicated various eye and lens
      abnormalities, including microphthalmia; underdeveloped iris, optic stalk,
      cornea, and retina; degenerated lens fibers with lost fibrillar structure; and
      vacuoles of various sizes at the posterior border of the lens. Mild opacity of
      the lens was found to progress with age and became denser, resembling mature
      cataract, and occupying the lens completely at the age of six to eight weeks. We,
      therefore, temporarily designated this abnormality as dense cataract and
      microphthalmia, with the gene symbol dcm.

PMID- 15253274
TI  - Mammary tumor heterogeneity in wt-ErbB-2 transgenic mice.
AB  - Phenotypic and biological heterogeneity was studied in a single transgenic mouse
      model to determine the level of biological variance. We analyzed 1,258 tumors
      from 417 MMTV-wt-ErbB-2 transgenic mice, subdivided by casein or soy-based
      dietary randomization and hormonal treatment. Variance in tumor histologic
      features, growth pattern, invasion, metastases, and multi-focality were detected
      in untreated and treated mice. Ninety-three percent (1,174/1,258) of tumors had
      the solid growth pattern widely reported in this model. However, among the solid
      tumors, a spectrum of growth patterns, from well-circumscribed tumors with a
      pseudocapsule to locally invasive or highly aggressive, metastatic subtype, was
      observed. Of the non-solid tumors, glandular features were prominent in 84 (7%).
      Adenocarcinomas included papillary, acinar/glandular, and adenosquamous subtypes.
      Adenosquamous tumors were exclusively observed in the group of mice treated on a
      short-term basis with estrogen. In contrast to the reported literature for this
      transgenic mouse model, mammary tumors were multifocal in the majority of cases
      (303 of 417 mice, or 73%). Results of this extensive study of a single transgenic
      model of mammary tumorigenesis indicate phenotypic and biological heterogeneity
      not previously associated with this transgenic mouse. These data support a
      complex, multistep process of carcinogenesis and clonal evolution, with
      biological and phenotypic variance similar to that observed in human mammary
      cancer development.

PMID- 15253275
TI  - Detection of lactate dehydrogenase-elevating virus by use of a fluorogenic
      nuclease reverse transcriptase-polymerase chain reaction assay.
AB  - Lactate dehydrogenase-elevating virus (LDEV) induces persistent infections in
      laboratory mice, alters in vivo physiology, and is a common contaminant of
      biological materials such as transplantable tumor cell lines. The fluorogenic
      nuclease reverse transcriptase polymerase chain reaction (fnRT-PCR) assay
      combines RT-PCR analysis with an internal fluorogenic hybridization probe,
      thereby eliminating post-PCR processing and potentially enhancing specificity. An
      fnRT-PCR assay specific for LDEV was therefore developed by targeting primer and
      probe sequences to a unique region of the LDEV nucleocapsid (VP1) gene. Using the
      LDEV fnRT-PCR assay, we detected only LDEV and did not detect other RNA viruses
      that are capable of naturally infecting rodents. Using this assay, we detected as
      little as 10 fg of LDEV RNA; the assay was 10-fold less sensitive when directly
      compared with the mouse bioassay (measurement of serum LD after inoculation),
      without the problematic false-positive serum LD enzyme elevations associated with
      the mouse bioassay. Using the fnRT-PCR assay, we also were able to detect viral
      RNA in numerous tissues and in feces collected from experimentally inoculated
      C3H/HeN mice, but we did not detect any viral RNA in similar samples collected
      from age- and strain-matched mock-infected mice. Finally, using the fnRT-PCR
      assay, we were able to detect LDEV RNA in biological samples that had previously
      been determined to be contaminated with LDEV by use of the mouse bioassay and an
      RT-PCR assay at another laboratory. In conclusion, the LDEV fnRT-PCR assay is a
      potentially high-throughput diagnostic assay for detection of LDEV in mice and
      contaminated biological materials.

PMID- 15253276
TI  - Analgesic efficacy of orally administered buprenorphine in rats: methodologic
      considerations.
AB  - Buprenorphine has been widely recommended for treatment of pain in rodents. We
      have previously documented that the recommended postoperative oral dose of
      buprenorphine in male Long-Evans rats, 0.5 mg/kg, is not as effective as the
      recommended parenteral dose of buprenorphine (0.05 mg/kg, s.c.) as an analgesic.
      In the series of experiments reported here, we compared: the analgesic effect of
      buprenorphine when prepared in two ways in the laboratory with that of a
      commercially available injectable solution of buprenorphine; the analgesic effect
      of buprenorphine in Long-Evans rats with that in Sprague-Dawley rats; and Long
      Evans and Sprague-Dawley rats for development of pica, a commonly reported side
      effect of buprenorphine. We followed the pica experiment with assessment of the
      effectiveness of buprenorphine in establishing a conditioned flavor aversion. The
      results indicated that method of preparation did not result in any significant
      differences in the efficacy of injected buprenorphine. Strain of rat was not
      associated with a significant difference in the efficacy of buprenorphine.
      However, a significant strain difference was found in development of pica.
      Buprenorphine treatment was effective in inducing a conditioned flavor aversion.
      We concluded that the recommended oral dose of buprenorphine (0.5 mg/kg) is
      ineffective as an analgesic, and that this was not the result of method of
      preparation of the buprenorphine or strain of rat used. Furthermore, we concluded
      that buprenorphine treatment may induce gastrointestinal distress in both strains
      tested. The results reaffirm our previous conclusion that oral administration of
      buprenorphine at 0.5 mg/kg, despite the general recommendation, is not a
      reasonable treatment for postsurgical pain in rats.

PMID- 15253277
TI  - Sex influence on chronic intestinal inflammation in Helicobacter hepaticus
      infected A/JCr mice.
AB  - Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to
      cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and
      immunodeficient mice. To the authors' knowledge, the influence of sex on
      development of chronic intestinal inflammation in H. hepaticus-infected mice has
      not been investigated. The purposes of the study reported here were to determine
      whether severity of intestinal inflammation differs between male and female A/JCr
      mice chronically infected with H. hepaticus and to characterize the mucosal
      immune response in these mice. The cecum of male and female A/JCr mice infected
      with H. hepaticus for 1 month and 3 months was objectively evaluated
      histologically for intestinal disease. Also, semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure
      interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha),
      interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha),
      interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma
      interferon (MIG) mRNA values in the cecal tissue of these mice. Significant
      differences in cecal lesion scores were not present at 1 month after infection.
      However, infected female mice had significantly up-regulated expression of cecal
      IL-10, MIP-1alpha, IP-10, and MIG mRNA compared with that in uninfected females,
      and expression of IL-10 and MIP-1alpha was significantly greater than that
      detected in infected male mice (P < or = 0.05). At 3 months after infection,
      cecal lesion scores were significantly (P < or = 0.05) increased in female and
      male mice compared with uninfected controls, and infected female mice had
      significantly (P < or = 0.05) higher cecal lesion scores than did infected male
      mice. In addition, infected females had significant (P < or = 0.05) increases in
      cecal IFN-gamma, TNF-alpha, IL-10, MIP-1alpha, IP-10, and MIG mRNA values
      compared with values in uninfected females and infected males, and male mice had
      significant (P < or = 0.05) increases in cecal TNF-alpha and IL-10 mRNA values
      compared with those for male control mice. These data indicate that, in H.
      hepaticus-infected A/JCr mice, females develop more severe intestinal
      inflammation than do males, and the chronic mucosal inflammation is polarized
      toward a Th1 response that is not down-regulated by increased activity of IL-10.
      We propose that H. hepaticus-infected A/JCr mice will serve as a good animal
      model with which to study the influence of sex on bacterial-induced mucosal
      inflammation.

PMID- 15253278
TI  - Characterization of a Mycobacterium ulcerans-like infection in a colony of
      African tropical clawed frogs (Xenopus tropicalis).
AB  - A nontuberculous Mycobacterium ulcerans-like organism was identified as the
      causative agent of an epizootic of mycobacteriosis in a colony of African
      tropical clawed frogs, Xenopus (Silurana) tropicalis, at the University of
      California, Berkeley. Diverse clinical signs of disease were observed, including
      lethargy, excess buoyancy, coelomic effusion, cutaneous ulcers, and granulomas.
      Visceral granulomas, ulcerative and granulomatous dermatitis, coelomitis, and
      septicemia were common findings at necropsy. Identification of M. ulcerans-like
      organisms was based on molecular and phenotypical characteristics. The findings
      of this investigation indicate that this M. ulcerans-like organism is a primary
      cause of morbidity and mortality in aquatic anurans and should be considered in
      the differential diagnosis of coelomic effusion in amphibians. Furthermore, if
      this Mycobacterium species ultimately is identified as M. ulcerans, X. tropicalis
      should be considered a potential source of this important public health pathogen.

PMID- 15253279
TI  - Urolithiasis associated with experimental lymphocytic choriomeningitis virus
      inoculation in Lewis rats.
AB  - A high frequency of struvite urolithiasis, hydronephrosis, and other urinary
      tract lesions developed in a group of Lewis rats inoculated intracranially with
      lymphocytic choriomeningitis virus (LCMV). Initially, clinically ill rats were
      referred to necropsy: 30 rats over 3 years. These rats had high frequency of
      urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%),
      transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). Lesions
      were more common in LCMV-inoculated rats. After this trend was noted, all rats on
      this protocol were necropsied as part of a cohort study (n = 144). Although the
      apparent frequency of disease was lower due to increased sampling, there still
      was a high number of urolithiasis (9/144, 6%) and hydronephrosis (40/144, 28%)
      cases. All cases of urolithiasis developed in rats inoculated with LCMV (9/44,
      20%), as did most cases of hydronephrosis (31/44, 70%). Although sham-injected
      and uninoculated control rats also had high frequency of hydronephrosis (6/57
      [11%] and 3/43 [7%], respectively), LCMV-inoculated rats had a significantly
      higher frequency of disease than did sham inoculated (P < 0.0001) and
      uninoculated (P < 0.0001) controls. These results suggest that Lewis rats may be
      predisposed to developing lesions of the urinary tract, and that intracranial
      inoculation of rats with LCMV augments this tendency, leading to formation of
      struvite calculi and associated urinary tract disease.

PMID- 15253280
TI  - Cecal volvulus in two African green monkeys (Cercopithecus athiops sabeus).
AB  - Following short-term signs of weakness, depression, and/or anorexia of less than
      24 h, two adult male African green monkeys (Cercopithecus aethiops sabeus) of St.
      Kitts origin died from complications of cecal volvulus. Gaseous distention was
      radiologically apparent in one animal. Necropsy of both monkeys revealed cecal
      volvulus, one at the ileocecal junction and one involving a segment of the distal
      portion of the ileum and cecum. Congestion and hemorrhage were evident
      microscopically in the lamina propria of the affected intestine, with variable
      necrosis.

PMID- 15253281
TI  - Radiation-induced glioblastoma multiforme in two adult baboons (Papio
      cynocephalus anubis).
AB  - A diagnosis of glioblastoma multiforme (GBM) was made for cerebral masses found
      at necropsy in two baboons (Papio cynocephalus anubis). Case 1 was an adult (6.18
      years old) male baboon that suddenly died during a physical examination as part
      of a clinical evaluation for a leg lameness. Case 2 was an adult (5.95 years old)
      female baboon that stopped breathing during anesthesia for an magnetic resonance
      imaging to evaluate lethargy, weight loss, inappetence, and dilated pupils. Both
      animals had undergone total body irradiation with cobalt during a research
      protocol. The incidence of spontaneous brain tumors in nonhuman primates is low,
      but radiation-induced GBM lesions in rhesus macaques (Macaca mulatta) have been
      reported. A definitive diagnosis was made in these cases, using histopathologic
      criteria of cellular pleomorphism, high mitotic rate, regions of coagulation
      necrosis, and endothelial proliferation.

PMID- 15253282
TI  - Carcinosarcoma of the maxilla in a squirrel monkey (Saimiri sciureus).
AB  - We present the first, to our knowledge, described case of carcinosarcoma of the
      maxilla in a squirrel monkey. Carcinosarcomas are rare tumors of the upper
      aerodigestive tract, and consist of carcinomatous and sarcomatous tissue.
      Histologic analysis revealed a neoplasm composed of an adenocarcinomatous
      component (epithelial element) and a mesenchymal component (sarcomatous element).
      Metastatic growth was documented in the lung tissue and the submandibular lymph
      node. The histolopathologic findings, the pattern of metastasis, and the clinical
      progression closely resembled those of carcinosarcoma involving salivary glands
      in humans.

PMID- 15253283
TI  - [Control of depression and suicidal risk in the elderly patient].

PMID- 15253284
TI  - [West Nile virus: in France again, in humans and horses].
AB  - West Nile virus (WNV) is a common arbovirosis, transmitted by mosquitoes mainly
      Culex. WNV is commonly responsible for equine epizootics and epidemics in humans
      in sub-Saharan Africa. It has been occasionally described in Southern Europe and
      in some Mediterranean countries. Since 1994, WNV clinical aspects seem to change
      with an increase of central neurological involvement and a higher mortality,
      especially among people older than 50 years. In 1999, WNV reached New York, being
      responsible for severe clinical manifestations. It spread all over North America
      in less than four years Four (only four states of the United States are free). As
      a consequence of an equine epizootic in Camargue in 2000, French medical
      authorities settled a survey of the WNV circulation in the South of France.
      During 2003, this efficient action led to identify 6 human cases in a formerly
      WNV-free French Mediterranean coast, but not in Camargue.

PMID- 15253285
TI  - [Monoclonal anti-CD20 antibody therapy].

PMID- 15253286
TI  - [Affective disorders in the elderly: how to better help and listen to our
      patients?].

PMID- 15253287
TI  - [Affective disorders specific to ageing].
AB  - With time, affects evolution can lead old people to a pathological organisation
      of their own mental universe. A general feeling of ill-being (syndrome of ageing
      badly) may appears and must be differentiated from an usual depressive syndrome.
      Post-traumatic disorders indicate a current or an old inability to metabolise
      painful life events. The "syndrome de glissement" (failure-to-thrive) generate
      not only bedridden state often irreversible but also guilt or depressive symptoms
      in caregivers. Those particular forms of ageing determine the relation with the
      practitioner and can induce feeling of dissatisfaction or hostility.

PMID- 15253288
TI  - [Depression in the elderly patient].
AB  - Depression is the most usual mental disorder in the elderly, but underdiagnosed
      and undertreated. Its prevalence is variable and depends on type and severity of
      episode. Nevertheless, even subsyndromic depression needs to be correctly
      treated. Depressive symptomatology observed in the elderly is often similar to
      adult presentation, but it can be masked and difficult to recognise. The
      different clinical features are described with underlining their particularities.
      Secondary depressions are also evoked with individualisation of "vascular"
      depression and its etiopathogenic hypotheses in relationship with observations
      given by cerebral neuro-imagery. Risk factors of depression in old age are known,
      but recent studies have reviewed some of them, particularly by distinguishing
      late onset depression and early onset depression. According to therapeutic
      response and prognosis, it appears necessary to better discriminate them. Risk of
      dementia after depression seems to be related with type of depressive episode and
      with the treatment efficacy. Finally, the problem of detection of depression in
      old age is discussed with a suggestion to use assessment instruments as the mini
      GDS in all medical practices, to optimise diagnosis and management.

PMID- 15253289
TI  - [Treatment of depression in the elderly].
AB  - Depression is the most common mental health problem of later life. There is
      effective treatments for depression in primary care. Recommendation based on
      current evidence are: in primary care treatment there is no evidence that one
      class of antidepressant is anymore effective than others; although newer
      antidepressants are not more effective than older ones, they are better tolerated
      in healthy older people and in patients with medical co-morbidity and are safer
      especially in overdose. Lower dose antidepressant treatment is not recommended
      for older depressed patients.

PMID- 15253290
TI  - [Love and sexuality in the elderly].
AB  - Love and sexuality in elderly are considered according to the psychoanalytical
      theory of libido, then distinguishing genital sexuality and its regressive or
      perverse forms. The ageing couple is presented through the psychopathology of
      widowhood and of conjoined burden in the couple.

PMID- 15253291
TI  - [Violence towards elderly persons].
AB  - Elder abuse is a common problem that affects 5% of the geriatric population.
      Authors describe many types of elder abuse: physical, emotional, financial and
      neglect (passive or active). The elderly are the fastest growing segment of the
      population in France. Consequently, the number of cases will likely increase as
      the geriatric population grows. Elder abuse receives less attention so only a few
      of these cases are reported. Elder abuse involves a complicated relationship
      among an individual's medical problems, social situation, and ability to function
      in the environment. The victims show typical risk factors such as living with the
      abuser, dependence on care, and cognitive impairment. The abusers live frequently
      in social isolation. Abuse is correlated with the emotional and financial
      dependence of the caregivers on their victims. Physicians are in ideal position
      to recognise, manage and help prevent elder mistreatment and neglect. To
      comprehensively evaluate elder abuse, a multidisciplinary approach is vital.
      Assessment and management should focus on both the patient and the caregiver.
      Patients with immediate danger should be hospitalised for safety and elder abuse
      be reported to the public attorney.

PMID- 15253292
TI  - [Depression in elderly persons].

PMID- 15253293
TI  - [Physicians' burnout].

PMID- 15253294
TI  - [Urinary incontinence in the adult. Diagnostic management].

PMID- 15253295
TI  - [Joint pain and effusions. Recent arthritic progression].

PMID- 15253296
TI  - [Appendicitis in the child and the adult].

PMID- 15253297
TI  - [Documentary research and self-instruction. Critical reading of a medical
      article. Practice guidelines. Part 1: rare diseases].

PMID- 15253298
TI  - [Prescription and surveillance of steroidal and non-steroidal anti-inflammatory
      drugs].

PMID- 15253299
TI  - [Prescription and surveillance of antithrombotic agents. Part 2: antiplatelet
      agents].

PMID- 15253300
TI  - [Evaluation of the severity and early complications. No 5: the thoracic trauma
      patient].

PMID- 15253301
TI  - [Women's lack of hygiene in XIXth century].

PMID- 15253302
TI  - Evidence for bovine immunodeficiency virus infection in cattle in Zambia.
AB  - We report herein on the first evidence for the presence of bovine
      immunodeficiency virus (BIV) in Zambia. Serological surveillance of BIV and
      bovine leukemia virus (BLV) was conducted in traditional cattle herds in Zambia.
      Out of a total of 262 sera analyzed, 11.4% were found positive for anti-BIV p26
      antibodies as determined by Western blot analysis, while 5.0% were positive for
      anti-BLV gp51 antibodies as detected by immunodiffusion test. Peripheral blood
      mononuclear cells from BIV seropositive cattle were found to have BIV-provirus
      DNA, as detected by nested polymerase chain reaction. A nucleotide sequence
      corresponding to a 298 bp fragment of the BIV pol gene was also analyzed. Amino
      acid sequences of these Zambian pol gene products showed 98.0 to 100% homology to
      the American strain BIV R29, 97.0 to 99.0% to Japanese BIV isolates, and
      divergence ranged from 0.0 to 2.0% among Zambian BIV isolates.

PMID- 15253303
TI  - Modern magnetic resonance: a hidden treasure of physical chemistry?

PMID- 15253304
TI  - Sensitivity enhancement in 1D heteronuclear NMR spectroscopy via single-scan
      inverse experiments.
AB  - Measuring the nuclear magnetic resonance spectra of low-gamma heteronuclei such
      as 15N constitutes an important analytical tool for the characterization of
      molecular structure and dynamics. The reduced resonance frequencies and magnetic
      moments of these heteronuclei, however, make the sensitivity of this kind of
      spectroscopy inherently lower than that of comparable H NMR observations. A well
      known solution to this sensitivity problem is indirect detection: a 2D NMR
      technique capable of enhancing the sensitivity of heteronuclear NMR by porting
      the actual data acquisition from the low-gamma nucleus to neighboring protons.
      This has become the standard method of observation in biomolecular NMR, where the
      resolution introduced by 2D spectroscopy is always a sought-after commodity.
      Indirect detection, however, has not gained a wide appeal in organic chemistry or
      in in vivo investigations, where one-dimensional heteronuclear NMR information
      usually suffices. The present study explores the possibility of retaining certain
      advantages derived from indirect detection while not giving up on the simple one
      dimensional nature of heteronuclear NMR, by relying on the spatial-encoding
      scheme we have recently demonstrated for implementing single-scan multi
      dimensional NMR spectroscopy. Preliminary results based on a 1D modification of
      this experiment confirm theoretical calculations suggesting that the sensitivity
      of 1D 15N NMR can be enhanced significantly in this manner; the relevance of this
      experiment given the advent of dedicated H-observing cryogenic probeheads with
      very high sensitivities is briefly discussed.

PMID- 15253305
TI  - Approximate solutions of the Bloch-McConnell equations for two-site chemical
      exchange.
AB  - Approximate formulas for the transverse-relaxation rate constant and resonance
      frequency have been derived for nuclear spins subject to two-site chemical
      exchange. The new results are more accurate than previous approximations when
      chemical exchange does not approach the fast-exchange limit or when site
      populations are not highly asymmetric. Results are derived from an effective
      average evolution operator that contains contributions from both exact
      eigenvalues of the Bloch-McConnell equations. These expressions are useful for
      interpretation of chemical exchange processes in NMR spectroscopy.

PMID- 15253306
TI  - Spectral deconvolution of chemical mixtures by covariance NMR.
AB  - A method is presented for the deconvolution of the NMR spectrum of a chemical
      mixture without requiring physical separation of its components. The method,
      which is termed "Demix", is based on a principal component analysis of a series
      of one-dimensional (1D) spectra that are statistically modulated during
      preparation and TOCSY mixing periods. The largest principal components correspond
      to the 1D NMR spectra of the scalar J-coupled spin networks of the individual
      components of the mixture. The method is demonstrated for aqueous mixtures of the
      amino acids Glu, Leu, Lys, and Val.

PMID- 15253307
TI  - Backbone-only protein solution structures with a combination of classical and
      paramagnetism-based constraints: a method that can be scaled to large molecules.
AB  - Herein, it is shown that a medium-resolution solution structure of a protein can
      be obtained with the sole assignment of the protein backbone and backbone-related
      constriants if a derivative with a firmly bound paramagnetic metal is available.
      The proof-of-concept is provided on calbindin D9k, a calcium binding protein in
      which one of the two calcium ions can be selectively substituted by a
      paramagnetic lanthanide ion. The constraints used are HN (and Ha) nuclear
      Overhauser effects (NOEs), hydrogen bonds, dihedral angle constriants from
      chemical shifts, and the following paramagnetism-based constraints: 1)
      pseudocontact shifts, acquired by substituting one (or more) lanthanide(s) in the
      C-terminal calcium binding site; 2) N-HN residual dipolar couplings due to self
      orientation induced by the paramagnetic lanthanide(s); 3) cross-correlations
      between the Curie and internuclear dipole-dipole interactions; and 4)
      paramagnetism-induced relaxation rate enhancements. An upper distance limit for
      internuclear distances between any two backbone atoms was also given according to
      the molecular weight of the protein. For this purpose, the paramagnetism-based
      constraints were collectively implemented in the program CYANA for solution
      structure determinations, similarly to what was previously done for the program
      DYANA. The method is intrinsically suitable for large molecular weight proteins.

PMID- 15253308
TI  - Determination of chemical shift anisotropy tensors of carbonyl nuclei in proteins
      through cross-correlated relaxation in NMR.
AB  - The principal components and orientations of the chemical shift anisotropy (CSA)
      tensors of nearly all 13C carbonyl nuclei in a small protein have been determined
      in isotropic solution by a combination of three complementary cross-correlation
      measurements.

PMID- 15253309
TI  - Principles of spin-echo modulation by J-couplings in magic-angle-spinning solid
      state NMR.
AB  - In magic-angle-spinning solid-state NMR, the homonuclear J-couplings between
      pairs of spin-1/2 nuclei may be determined by studying the modulation of the spin
      echo induced by a pi-pulse, as a function of the echo duration. We present the
      theory of J-induced spin-echo modulation in magic-angle-spinning solids, and
      derive a set of modulation regimes which apply under different experimental
      conditions. In most cases, the dominant spin-echo modulation frequency is exactly
      equal to the J-coupling. Somewhat surprisingly, the chemical shift anisotropies
      and dipole-dipole couplings tend to stabilise--rather than abscure--the J
      modulation. The theoretical conclusions are supported by numerical simulations
      and experimental results obtained for three representative samples containing 13C
      spin pairs.

PMID- 15253310
TI  - High-performance selective excitation pulses for solid- and liquid-state NMR
      spectroscopy.
AB  - Computer-optimized selective pulses are routinely used in solution-state NMR
      spectroscopy. At the same time, their utility and importance for solid-state
      applications has yet to be fully realized. We suggest a new computational
      approach that makes the design of soft selective pulses with desired properties
      relatively straightforward. By applying this technique to the generic selective
      excitation problem, we have arrived at a family of high performance selective
      excitation pulses, dubbed E-Family, that allows more flexibility and better
      performance than analogous pulses previously reported in the literature. The new
      pulses have been successfully tested in both solid- and solution-state NMR
      experiments. A theoretical treatment of the effects of chemical shift anisotropy
      (CSA) on the selective excitation in magic-angle spinning (MAS) experiments in
      solids is presented. The set of heuristics that comprise our new strategy were
      incorporated into a general NMR simulation program SPINEVOLUTION.

PMID- 15253311
TI  - Polarization-transfer methods in solid-state magic-angle-spinning NMR: adiabatic
      CN pulse sequences.
AB  - An adiabatic double-quantum polarization-transfer experiment is described. It can
      be characterized as an adiabatic variant of the POST-C7 experiment. A continuous
      variation of the phase increment between pulses leads to the introduction of a
      fictitious Zeeman field that allows for an adiabatic passage through the
      recoupling condition. This results in a chemical-shift-offset-compensated
      adiabatic experiment, which leads to an efficient and broadbanded polarization
      transfer or to a double-quantum excitation. Similar variations of other C- or R
      type experiments can be envisioned.

PMID- 15253312
TI  - Sensitivity enhancement in two-dimensional solid-state NMR spectroscopy by
      transverse mixing.
AB  - The sensitivity of two-dimensional (2D) 13C-13C solid-state NMR spectroscopy
      under magic-angle spinning (MAS) is shown to be enhanced by the use of transverse
      polarization transfer in place of the conventional longitudinal polarization
      transfer. Experimental results are reported for 2D spectroscopy of a 20-residue,
      filament-forming peptide derived from the E. Coli RecA protein, containing five
      uniformly 13C-labeled residues, performed at 14.1 T with high-speed MAS and with
      finite-pulse radio-frequency-driven recoupling of dipolar interactions in the
      mixing period. Significant sensitivity enhancements observed at short mixing
      periods results from a more rapid build-up of cross-peaks under transverse mixing
      than under longitudinal mixing and from the 2 gain inherent in 2D measurements in
      which both orthogonal transverse polarization components in the t1 period
      contribute to each free-induction decay signal detected in the t2 period.

PMID- 15253313
TI  - Transverse dephasing optimised NMR spectroscopy in solids: natural-abundance 13C
      correlation spectra.

PMID- 15253314
TI  - Complex morphology of melt-spun nylon-6 fibres investigated by 1H double-quantum
      filtered NMR spin-diffusion experiments.
AB  - The complex morphology of high-speed melt-spun nylon-6 fibres hydrated with D2O
      was investigated using 1H double-quantum-filtered spin-diffusion NMR experiments.
      The magnetisation exchange from selected crystalline domains along the fibrils
      and interfibrils was simulated with the help of a three-dimensional solution of a
      spin-diffusion equation approximated by a product of one-dimensional analytical
      NMR signals, which correspond to a lamellar morphology. This allows to measure
      the sizes of crystalline and less-mobile amorphous domains along the fibrils, as
      well as the diameter of the fibrils and interfibril distances. A series of nylon
      6 fibres with extreme values of winding speed and draw ratio was investigated.
      The changes detected in the domain size along the fibrils and interfibrils show
      the same trend in the data obtained from wide-angle X-ray diffraction and small
      angle X-ray scattering.

PMID- 15253315
TI  - Polymer dynamics under nanoscopic constraints: the "corset effect" as revealed by
      NMR relaxometry and diffusometry.
AB  - A spinodal demixing technique was employed for the preparation of linear
      poly(ethylene oxide) (PEO) confined in nanoscopic strands, which in turn are
      embedded in a quasi-solid methacrylate matrix impenetrable to PEO. Both the
      molecular weight of the PEO and the mean diameter of the strands are variable to
      a certain degree. Chain dynamics of the PEO in the molten state were examined
      with the aid of field-gradient NMR diffusometry and field-cycling NMR
      relaxometry. The dominating mechanism for translational displacements in the
      nanoscopic strands is shown to be reptation. A formalism for the evaluation of
      NMR diffusometry is presented, which permits the estimation of the mean PEO
      strand diameter. Samples of different composition revealed diameters in the range
      9-58 nm, in reasonable agreement with electron micrographs. The time scale of the
      diffusion measurements was 10-300 ms. On the much shorter time scale of field
      cycling NMR relaxometry, 10(-9)-10(-4)s, a frequency dispersion of the spin
      lattice relaxation time characteristic for reptation clearly showed up in all
      samples. An effective tube diameter of only 0.6 nm was found even when the strand
      diameter was larger than the radius of gyration of the PEO chain random coils.
      The finding that the tube diameter effective on the short time scale of field
      cycling NMR relaxometry is much smaller than the diameter of the confining
      structure is termed the "corset effect", and is traced back to the lack of local
      free-volume fluctuation capacity under nanoscale confinements. The order of
      magnitude of the 'pore' diameter, at which the cross-over from confined to bulk
      chain dynamics is expected, is estimated.

PMID- 15253316
TI  - Rotor modulations and recoupling strategies in 13C solid-state magic-angle
      spinning NMR spectroscopy: probing molecular orientation and dynamics.
AB  - Recoupling strategies for anisotropic interactions enable the investigation of
      molecular structure, order and dynamics in a sensitive and site-specific fashion
      by solid-state NMR spectroscopy. Whereas magic-angle spinning (MAS) efficiently
      averages anisotropic interactions and enhances spectral resolution, recoupling
      pulse sequences selectively restore certain parts of rotor-modulated dipole
      dipole couplings or chemical shift anisotropies (CSA). More specifically, it is
      possible to recouple either the omegaR- or the 2omegaR-modulated terms of an
      interaction Hamiltonian, which exhibit different orientation dependencies and, in
      this way, provide a means of distinguishing whether the observed NMR spectra are
      affected by molecular motion or by molecular orientation. Sideband patterns
      generated by reconversion rotor encoding allow for a precise and selective
      determination of coupling constants and anisotropies, which contain site-specific
      information on structure, orientation and/or dynamics of individual molecular
      segments. Corresponding recoupling schemes are presented in a common context, and
      the possibilities of exploiting these effects for the determination of order
      parameters of oriented materials, such as oriented polymer chains or extruded
      fibres of a discotic mesogen, are discussed. The obtained orientational order
      parameters are compared to results from two-dimensional wide angle X-ray
      scattering (WAXS).

PMID- 15253317
TI  - Who'd want to be a surgeon?

PMID- 15253318
TI  - Sentinel lymph node biopsy in breast cancer--a learning curve.

PMID- 15253319
TI  - Diagnosis and surgical treatment of intrabiliary ruptured hydatid disease of the
      liver.
AB  - BACKGROUND AND OBJECTIVES: The major complication of hydatid disease of the liver
      is intrabiliary rupture of the cyst. The purpose of this study was to evaluate
      the outcome of patients with intrabiliary ruptured hydatid disease of the liver.
      METHOD: Using a standardised data collection instrument, case records of patients
      who were operated on for hydatid disease of the liver diagnosed between January
      1990 and December 2001 at Dicle University Hospital (DUH) were searched and 192
      patients who had been operated for hydatid disease of the liver were detected. Of
      these, 20 patients (16 females, 4 males) were retrospectively reviewed for
      intrabiliary ruptured hydatid disease of the liver. RESULTS: Intrabiliary
      ruptured hydatid disease of the liver was determined in 10.4% (N = 20) of the
      patients (N = 192) operated for hydatid disease of the liver. The average age of
      patients was 38.9 +/- 14.05 years (range 20 - 72 years). The duration of the
      symptoms was 3.4 +/- 2.13 years (range 1 - 8 years). The most frequent symptoms
      were right upper quadrant/epigastric pain, dyspepsia, jaundice and pruritus.
      Diagnosis of hydatid cyst was principally made using ultrasonography. Twelve
      cysts (60%) were located in the right lobe, 5 (25%) in the left lobe, and 3 (15%)
      in the right and left lobes. The size of the cysts was 12.6 +/- 5.79 cm (range 6 
      20 cm). The average diameter of the common bile duct (CBD) was 20.45 +/- 8.54 mm
      (range 10 - 40 mm). Dilated CBD in 16 patients (80%) and daughter cysts and
      debris in the CBD in 10 patients (50%) were found during operation. Partial
      cystectomy and capitonnage were performed in all patients. In addition, T-tube
      drainage in 17 patients, omentoplasty plus T-tube drainage in 2 patients and
      choledochoduodenostomy in 1 patient were carried out during operation. An
      internal opening of the biliary fistula was found and sutured in 12 patients
      (60%). Wound infections developed in 6 patients (30%), suppuration of the
      residual cavity in 4 patients, and wound dehiscence in 2 patients. Two patients
      (10%) died from sepsis-multiple organ failure and hepatic failure. The average
      period of hospitalisation was 28.75 +/- 19.1 days (range 10 - 103 days).
      CONCLUSIONS: If bile-stained cystic fluid and a dilated CBD is found in patients
      with hydatid disease of the liver, choledochal exploration should be performed
      during operation. T-tube drainage may be preferred in the management of
      intrabiliary ruptured hydatid disease because of low morbidity, the ability to
      decompress intrabiliary pressure, easier monitoring of the biliary drainage and
      smaller alteration of the anatomy.

PMID- 15253320
TI  - Immediate endovascular stent-graft repair of an acute traumatic rupture of the
      thoracic aorta: case report and subject review.
AB  - We describe a case of emergency endovascular stent-graft placement for acute
      traumatic rupture of the thoracic aorta in a patient with an associated unstable
      type II odontoid fracture. The stent-graft placement procedure was performed
      within 4 hours of admission under sedation and local anaesthesia while the neck
      remained externally splinted. After exclusion of the rupture the patient could
      then undergo treatment of the associated cervical fracture and other injuries.

PMID- 15253321
TI  - Pancreaticoduodenostomy for treatment of giant duodenal ulcer.

PMID- 15253322
TI  - Alterations in acid-base homeostasis with aging.

PMID- 15253323
TI  - Racial differences in analgesic/anti-inflammatory medication use and perceptions
      of efficacy.
AB  - BACKGROUND AND OBJECTIVE: Pharmacotherapy is a key component to osteoarthritis
      (OA) treatment. Research has shown important racial differences in pain
      thresholds and perceptions, but little is known about racial variations in
      responses to pain medications. The purpose of this study was to compare
      perceptions of efficacy of pain medications among African-American and Caucasian
      veterans with OA. METHODS: Participants (N = 202; 70% Caucasian, 30% African
      American) were under care for OA within the VA healthcare system. Participants
      rated the helpfulness of current analgesic/anti-inflammatory medications (scale
      of 1--not at all helpful to 10--very helpful). RESULTS: The mean rating of
      medication helpfulness was 6.1. African-American participants reported
      significantly greater ratings of medication helpfulness than Caucasians (6.6 vs.
      5.9), controlling for demographics, disease severity, total number of
      analgesic/anti-inflammatory medications being taken, and the class of the
      medication. CONCLUSION: African Americans had somewhat more favorable perceptions
      of medication helpfulness than Caucasians. However, overall ratings of medication
      helpfulness were relatively low. Further research is needed to examine whether
      modifiable factors (such as low dosing or patient nonadherence to prescription
      instructions) contribute to perceptions of poor efficacy.

PMID- 15253324
TI  - End-of-life choices for African-American and white infants in a neonatal
      intensive-care unit: a pilot study.
AB  - BACKGROUND: African-American adults are more likely than white adults to desire
      the continuation of life-sustaining medical treatment (LSMT) at the end of life.
      No studies have examined racial differences in parental end-of-life decisions for
      neonates. OBJECTIVE: To collect preliminary data to determine whether differences
      exist in the choices made by parents of African-American and white infants when a
      physician has recommended withholding or withdrawing LSMT from their infant to
      develop hypotheses for future work. DESIGN/METHODS: A retrospective chart review
      of African-American and white infants who died in an urban neonatal intensive
      care unit (NICU) over a two-year period. Charts were abstracted for demographics,
      cause of death, and documentation of meetings where the physician recommended
      withholding or withdrawing LSMT. RESULTS: Thirty-eight infant charts met study
      criteria (58% African-American, 42% white). Documentation of physician
      recommendations to limit LSMT was present in 61% of charts. Approached families
      of white infants agreed to limit LSMT 80% of the time compared to 62% of the
      families of African-American infants. CONCLUSIONS: In this pilot study, parents
      of African-American and white infants appeared to make different end-of-life
      choices for their children. A larger study is needed to confirm these findings
      and further explore contributing factors such as mistrust, religiosity, and
      perceived discrimination.

PMID- 15253325
TI  - Racial influence on biochemical disease-free survival in men treated with
      external-beam radiotherapy for localized prostate cancer.
AB  - BACKGROUND: We retrospectively analyzed the clinical characteristics and outcomes
      of various racial and ethnic groups who underwent radiotherapy alone for
      localized or locally advanced prostate cancer. METHODS: From April 1987 to
      January 1998, 964 patients underwent full-dose, external-beam radiotherapy alone
      for localized or locally advanced prostate cancer and were included in the study.
      The patients' medical records were reviewed for pertinent information. RESULTS:
      Of the 964 patients, 810 were non-Hispanic white, 86 were African-American, 54
      were Hispanic, and 14 were Asian. The most significant difference between groups
      was in the proportion of patients who presented with initial PSA levels > 20
      ng/ml. More than 20% of men in all minority groups presented with a serum PSA >
      20 ng/ml, compared to only 11% of whites (p = 0.0012). Similarly, 14% of
      minorities presented with Gleason scores > or = 8 compared to only 11% of whites
      (p = 0.0265). Hispanic and Asian patients exhibited a higher incidence of Gleason
      score > or = 8 prostate cancer. When comparing the time intervals of 1995-1998
      vs. 1987-1994, the number of men presenting for EBRT with PSA levels < 10 ng/ml
      increased to 74% from 57% for Caucasians (p < 0,001), 71% from 40% for African
      Americans (p = 0.012), 67% from 49% for Hispanics (p = 0.1 18), and no change
      (50%) for Asians. CONCLUSIONS: The number of African-American patients presenting
      with favorable characteristics (PSA < 10 ng/ml) is increasing. These findings
      suggest that the message of screening and early detection may be reaching the
      African-American community. Continued diligence in screening and early detection
      may improve prostate cancer outcome for other minority populations.

PMID- 15253326
TI  - Steroids and antibiotics for treatment of acute asthma exacerbations in African
      American children.
AB  - BACKGROUND: There has been great debate surrounding the appropriate treatment
      regimens in children who present with acute asthma exacerbations secondary to
      upper respiratory tract infections. OBJECTIVE: To determine whether treatment
      with corticosteroids alone or in combination with antibiotics will decrease
      respiratory symptoms in children who develop asthma exacerbations secondary to
      upper respiratory tract infections. METHODS: A retrospective cohort control study
      involving 86 African-American children, ages 5-16, with mild intermittent asthma.
      The patients were treated with an albuterol inhaler (control group), inhaler plus
      five days of Prednisone; or inhaler, Prednisone, and 10 days of Amoxicillin. All
      patients were assessed regarding peak flows, albuterol inhaler usage, and
      symptomatology. RESULTS: On follow up five- to seven days after presentation, the
      corticosteroids group demonstrated a marked improvement in peak flows (88% versus
      77%) and a significantly lower albuterol inhaler usage rate (2.2 versus 3.7 times
      a day) relative to the control group. The corticosteroids plus antibiotics group
      demonstrated peak flows (86% versus 88%) and inhaler usage (2.4 versus 2.2)
      nearly identical to corticosteroids alone, but the severity of underlying
      respiratory symptoms was significantly less. CONCLUSION: A five-day course of
      oral corticosteroids will significantly improve lung function and lessen severity
      of asthma symptoms. The addition of antibiotics to the treatment regimen has no
      additive effect on the reactive airway symptoms.

PMID- 15253327
TI  - Community asthma education program for parents of urban asthmatic children.
AB  - OBJECTIVES: To demonstrate the effectiveness of community asthma education
      provided by peers in the urban community. METHOD: A convenience sample of 267
      self-referred, primarily African-American parents or primary caregivers of
      asthmatic children aged 18 months to 16 years completed a five-session education
      program. Program efficacy was evaluated at baseline, immediately postinstruction,
      and at three-, six-, and 12 months retention. Outcomes included three
      questionnaires measuring asthma self-management knowledge, control and quality of
      life. RESULTS: Immediately following program completion, participants
      demonstrated improvements in asthma knowledge (13% increased proportion correct,
      p < 0.01), ability to control their child's asthma 16% increased score, p <
      0.01), and asthma quality of life (7% increased score, p < 0.01). Retention of
      knowledge with steady improvement of control and quality of life was observed up
      to one year postinstruction, as compared with immediate postprogram scores (p =
      0.09 and 0.05, respectively). CONCLUSIONS: A community-based asthma educational
      program for caregivers should be an important component of childhood asthma
      management. The complexities of asthma management are best taught in educational
      programs that are easily accessible, provide a comfortable environment for
      participants, and are taught by peers.

PMID- 15253328
TI  - Black and white patients fare equally well when treated with postlumpectomy
      radiotherapy.
AB  - PURPOSE: Some previous studies have demonstrated that black patients have
      inferior local-regional control and disease-free survival when treated with
      postlumpectomy radiotherapy. The intention of this study was to analyze the same
      outcomes with a larger series of black patients. METHODS: A retrospective chart
      review was performed at an academic referral center, a community hospital, and an
      inner-city public hospital. RESULTS: A total of 270 patients that received
      postlumpectomy radiotherapy were reviewed. Of those, 102 were black, 162 white,
      and six nonblack, nonwhite. The black patients were statistically significantly
      more likely to present with higher-stage disease (Stage II: 43.1% vs. 32.1%),
      positive lymph nodes (29.4% vs. 14.8%), higher-grade disease (Grade III: 35.3%
      vs. 24.1%), and age < 45. The actuarial local control at five years in the black
      patients was 95.5% and in the white patients was 94.8%. The actuarial five-year
      disease-free survival in the black patients was 90.3% and in the white patients
      was 91.7%. There was no statistically significant difference in either local
      control or disease free-survival in the black and white patients when matched by
      stage. CONCLUSION: At five years, the local control and disease-free survival for
      black patients are equally as good as white patients.

PMID- 15253329
TI  - Diastolic dysfunction in persons with hypertensive heart failure.
AB  - Arterial hypertension is the commonest cause of heart failure in the Savannah
      region of Nigeria. The prevalence of diastolic dysfunction in patients with
      hypertensive heart failure in this region is unknown. This needs to be
      determined, since it may influence therapy. Left ventricular function of 95
      patients with hypertensive heart failure and 92 age-/sex-matched, healthy
      normotensive control was determined by echocardiography using ALOKA SSD 1700 two
      dimensional echocardiograph/ Doppler and color flow ultrasound machine. Compared
      to the controls, the hypertensive heart failure patients had increased left
      ventricular mass index (LVMI), p = 0.0001; cardiothoracic ratio (CTR), p =
      0.0001; and electrocardiographic left ventricular hypertrophy (ECG-LVH), p =
      0.0001. Isolated diastolic dysfunction, E/A ratio < 1.0, and EF > 50%, was seen
      in 12 patients (12.6%). Twenty-three patients (24.2%) had combined diastolic and
      systolic dysfunction (E/A ratio < 1.0 and EF < 50%). Six patients (6.3%) had
      pseudonormalization (E/A ratio 1.0-2.0 and deceleration time, DT, 150-200 msec),
      while restrictive pattern of diastolic dysfunction was seen in 25 patients
      (26.3%). This prevalence of 69.4% of diastolic dysfunction in Nigerians with
      hypertensive heart failure seen in this study emphasizes the need for Doppler
      echocardiographic evaluation and diagnosis where these facilities are available.
      This will aid the physician to prescribe appropriate treatment.

PMID- 15253330
TI  - Prevalence of Parkinson's disease in populations of African ancestry: a review.
AB  - There have been a number of studies looking at the prevalence of Parkinson's
      disease (PD) in different racial and geographical populations. Some of the
      earliest studies suggested a difference in the prevalence of PD in African
      Americans as compared with Caucasians. As such a difference would have important
      implications for healthcare and research into the etiology of PD, we undertook a
      review of published studies to determine whether evidence suggested that such a
      difference exists. We reviewed 20 studies that looked at incidence, prevalence,
      and percentages of neurology patients with PD and Parkinsonism in Africa and in
      African-American populations. Two of these were door-to-door studies that relied
      on questionnaires for initial ascertainment, another was performed by review of
      outpatient records of a large health maintenance organization, while the
      remainder were based on hospital admissions, diagnosis in the community, or death
      certificate reports. In the aggregate, these studies suggest PD may be less
      frequent among Africans and African Americans than among Caucasians, although the
      most well-designed study showed only a statistically insignificant reduction in
      the prevalence of PD among African Americans. Although an apparently lower
      disease frequency among people of African origin may have a basis in the
      pathobiology of the disease, nearly all of these studies were vulnerable to a
      variety of ascertainment biases, and many lacked stringent application of
      diagnostic criteria applied by specialists trained in movement disorders. We
      conclude that a difference in the prevalence of PD and Parkinsonism between black
      and other populations is unproven and will require additional well-designed
      studies to determine if previously reported ethnic differences in disease
      prevalence are real.

PMID- 15253331
TI  - Web of science: a unique method of cited reference searching.
AB  - The number of times an article is acknowledged as a reference in another article
      reflects its scientific impact. Citation analysis is one of the parameters for
      assessing the quality of research published in scientific, technology and social
      science journals. Web of Science enables users to search current and
      retrospective multidisciplinary information. Parameters and practical
      applications evaluating journal and article citation characteristics available
      through the Science Citation Index are summarized.

PMID- 15253332
TI  - Outpatient management of sickle cell pain with chronic opioid pharmacotherapy.
AB  - We report our experience of providing chronic opioid pharmacotherapy on an
      outpatient basis to selected patients with frequent episodes of moderate-to
      severe pain from sickle cell disease (SCD). Three cases illustrate our clinical
      experience in approximately 40 patients with sickle cell pain. Patients were seen
      at our sickle cell pain clinic at Beth Israel Hospital once each month for a
      three-hour visit. Visits included group music therapy and individual medical
      care, including comprehensive blood work and scheduling of medical tests when
      appropriate. Between visits, the pain and palliative care physicians followed
      patients on an as-needed basis. The SCD pain opioid pharmacotherapy protocol was
      modeled on a regimen used to treat malignant pain-typically a long-acting opioid
      in combination with a short-acting opioid, such as oral transmucosal fentanyl
      citrate (OTFC; Actiq) for breakthrough pain (BTP). Emergency department (ED)
      visits and hospital admissions were dramatically reduced in the three patients
      whose pain was managed by adapting the cancer pain model. During the year before
      their first visit to our pain clinic, the patients each had between six and 18 ED
      visits, which resulted in six- to 13 hospital admissions amounting to 32-182
      inpatient days per patient. Each of the patients was prescribed a long-acting
      opioid (methadone, control-release oxycodone, or transdermal fentanyl) with a
      short-acting opioid for BTP from crises (oral transmucosal fentanyl citrate for
      two patients; short-acting oxycodone for one patient). Pain was well controlled.
      For each patient, hospital admissions were reduced to < or = 1 visit per year.
      These reduced levels of ED visits and hospital admissions have remained constant
      for more than three years.

PMID- 15253333
TI  - Generations of loss: contemporary perspectives on black infant mortality.
AB  - The U.S. black infant mortality rate (IMR) remains a significant public health
      concern. Although improved during the last four decades, the U.S. IMR remains
      within the lowest tier of IMRs for all industrialized countries, and black
      American infants remain disproportionately represented in low birthweight (LBW)
      and infant death statistics. Numerous risk factors have been analyzed for their
      relative contributions to the U.S. IMR and black-white infant survival health
      disparities. Those factors include prenatal care quality and access, maternal
      socioeconomic status (SES), HIV/AIDS status, infections, intrapartum risk
      factors, existing comorbidities, social support, and nutritional status. However,
      the role of these and other factors have not fully explained the higher infant
      mortality risks for black infants. This review will discuss a variety of risk
      factors that contribute to infant mortality disparities between non-Hispanic
      black and white infants. Among those factors, the goal will be to review selected
      topics pertaining to maternal SES, LBW, preterm birth, perinatology advances,
      birth record data quality, maternal stress, prenatal care adequacy, and physical
      and substance abuse, and the relationships of those topics to black-white IMR
      health disparities.

PMID- 15253334
TI  - Cardiotoxicities of paclitaxel in African Americans.

PMID- 15253335
TI  - [Quality control of an early detection, diagnosis and early intervention program
      for deafness in newborn. Official document of the Early Detection Comission of
      Deafness in Newborn (CODEPEH)].

PMID- 15253336
TI  - [Otologic determining factors on infra-red tympanic thermometry in children].
AB  - OBJECTIVE: To evaluate the influence of different otoscopic findings on body
      thermometry in children using an infra-red tympanic thermometer. PATIENTS AND
      METHODS: Body temperature was measured on healthy right and left ear canals with
      Thermoscan systems. Moreover, it was determined on children with altered
      otoscopy, companng to normal contralateral ear. To assess its diagnostic
      fiability, accuracy ratios were calculated in different temperatures. RESULTS:
      Temperature measured bilaterally did not offer differences, and intra/interassay
      variation ratios were always less than 0.34%. Acute otitis externa increased
      tympanic thermometry a mean of 0.36 degrees C (p < 0.001), and cerumen and
      previously radical surgery decreased a mean of 0.62 and 0.53 degrees C,
      respectively (p < 0.001). CONCLUSIONS: The conditions mentioned before modify
      body thermometry if measured by infra-red tympanic thermometer. So, this system
      must be avoided in these circumstances. Otitis media, fluid in middle ear,
      tympanic perforation and ventilation tubes did not modify thermometric results.

PMID- 15253337
TI  - [Elective mastoidectomy with reconstruction of the posterior wall or filling of
      mastoid cavity. Results].
AB  - From the 80's and facing the different approaches available to asses which one
      offered more benefits between all of them, the surgery to the demand has its
      place. The objective of this work is to determine the audio-surgical results in
      the patients with aticomastoidectomy to demand with reconstruction of later wall
      or stuffing of the mastoid cavity, and to show the results three years later. A
      prospective and descriptive study in 22 patients who underwent a mastoidectomy to
      demand using outologous cartilage for the reconstruction of the later wall, and
      bone powder obtained from the surgical drilling to fill up the mastoid cavity.

PMID- 15253338
TI  - [Evaluation of a family with sensorineural hearing loss due to the Q829X mutation
      in the OTOF gene].
AB  - OBJECTIVE: To determine the features of hearing loss due to the Q829X mutation in
      the OTOF gene, the third most frequent mutation causing prelingual deafness
      reported so far in the Spanish population. MATERIALS AND METHODS: We carried out
      genetic characterisation of 16 individuals from a consanguineous family from
      Cantabria, in which 4 members were affected by deafness. RESULTS: All 4 hearing
      impaired individuals were homozygous for the Q829X mutation in the OTOF gene. The
      auditory defect was a profound, bilateral, symmetrical, sensorineural hearing
      loss of prelingual onset. No other clinical alterations were observed.
      Individuals heterozygous for the Q829X mutation were unaffected. CONCLUSIONS: The
      Q829X mutation in the OTOF gene causes severe to profound sensorineural hearing
      loss of prelingual onset. Early detection of individuals carrying this mutation
      is important for the application of palliative treatment and special education.

PMID- 15253339
TI  - [Cerebellopontine angle and internal auditory canal lipomas: report of four cases
      and review of the literature].
AB  - AIM: Lipomas are exceptional tumors at the Cerebellopontine Angle (CPA) or the
      Internal Auditory Canal (IAC). We evaluate clinical, histological and
      radiological characteristics of the cases diagnosed in our Hospital and the
      results of conservative versus surgical treatment. MATERIAL AND METHODS: We
      report 4 cases of CPA and/or IAC and review 99 previously reported in the
      literature. RESULTS: Unilateral tinnitus was the most frequent symptom (100%).
      All lesions showed hyperintensity on T1 and hypo/isointensity on T2--weighted MNR
      images. Two patients underwent a retro-sigmoidal approach without complete
      tumoral resection and with additional neurological consequences. Another two
      cases were followed up by annual MNRs. During the follow-up period (4.2 years
      average), neither clinical nor radiological changes were detected. CONCLUSION:
      The surgical resection of CPA y/o IAC lipomas is associated to a significant
      morbidity due to the high vascularization and the dense adherence of these
      lesions to the surrounding tissues. The MNR is the suitable technique for
      differential diagnosis between lesions at this location.

PMID- 15253340
TI  - [Histopathological changes at the surgical site in experimental animals following
      partial cricoid resection and thyrotracheal anastomosis].
AB  - OBJECTIVE: To study in an animal model the local healing process after partial
      cricoid resection with thyrotracheal anastomosis. MATERIAL AND METHODS: Partial
      cricoid resection with thyrotracheal anastomosis was performed in 17 New Zealand
      rabbits. Experimental animals were gradually sacrificed and the laryngotracheal
      complex was removed to proceed to a histopathological study. RESULTS: An acute
      inflammatory response followed by a chronic inflammatory process was found in the
      surgical site. Normal tissue architecture was established after an eight week
      period. Anteroposterior and transverse diameters at all levels of the upper
      respiratory tract were not significantly altered at any time along the healing
      process. Experimental animals remained free from symptoms during the follow-up
      period. CONCLUSIONS: These results support that partial cricoid resection with
      thyrotracheal anastomosis is a safe procedure for the treatment of severe
      laryngotracheal stenosis.

PMID- 15253341
TI  - [DNA extraction using Chelex resin for oncogenic amplification analysis in head
      and neck tumours].
AB  - DNA extraction from tissues can be the most laborious and complex step in
      amplifying DNA by PCR when phenol-choroform procedure is used. We compare this
      lengthy, slow and expensive extraction method with other two based in the use of
      Chelex-100 resin. This chelating resin has been applied for extracting DNA from
      different tissues to use with the PCR. These procedures are simple, rapid and do
      not require multiple steps. In this study we compared DNA extraction from 30 head
      and neck squamous cell carcinomas (HNSCC) using organic solvent precipitation,
      Chelex 100 resin with and without proteinase K pretreatment. The results show
      that proteinase K-Chelex 100 procedure is as efficient as the phenol-chloroform
      one.

PMID- 15253342
TI  - [Ciliary changes with abscence of dynein arms in Kartagener's syndrome].
AB  - A 33 years-old female with a diagnosis of Kartagener's syndrome was studied. She
      had a clinical history of chronic sinusitis with nasal obstruction and rhinorrea,
      and a chronic cough with mucopurulent sputum. A paranasal sinus CT showed
      hypertrophyc mucosa. A thoracic CT showed a situs inversus and chronic bronchitis
      with bronchiectasis. The saccharin test lasted 55 minutes. The electron
      microscopy study showed in a a cross-sectional axoneme a total absence of the
      outer and inner arm of the 9th outer doublet in over a 100 cilias studied. No
      others ultrastructure anormalities were observed.

PMID- 15253343
TI  - [Cervicothoracic angiomyolipoma: an unusual tumor located at a site difficult to
      reach for surgery].
AB  - Angiomyolipoma is an uncommon hamartomatous renal tumor very prone to spontaneous
      bleeding. However it is possible to find it in extrarenal sites, being the liver
      the most frequent one. The rest of sites recorded in literature are exceptional.
      In fact, to our knowledge, this is the first case reported of cervicothoracic
      settlement of an angiomyolipoma. This rare location, together with its marked
      tendency to bleed bleeding determinate a complicated diagnoses a difficult
      surgical approach.

PMID- 15253344
TI  - Introduction. Taxonomy for the twenty-first century.

PMID- 15253345
TI  - Taxonomic triage and the poverty of phylogeny.
AB  - Revisionary taxonomy is frequently dismissed as merely descriptive, which belies
      its strong intellectual content and hypothesis-driven nature. Funding for
      taxonomy is inadequate and largely diverted to studies of phylogeny that neither
      improve classifications nor nomenclature. Phylogenetic classifications are
      optimal for storing and predicting information, but phylogeny divorced from
      taxonomy is ephemeral and erodes the accuracy and information content of the
      language of biology. Taxonomic revisions and monographs are efficient, high
      throughput species hypothesis-testing devices that are ideal for the World Wide
      Web. Taxonomic knowledge remains essential to credible biological research and is
      made urgent by the biodiversity crisis. Theoretical and technological advances
      and threats of mass species extinctions indicate that this is the time for a
      renaissance in taxonomy. Clarity of vision and courage of purpose are needed from
      individual taxonomists and natural history museums to bring about this evolution
      of taxonomy into the information age.

PMID- 15253346
TI  - A taxonomic wish-list for community ecology.
AB  - Community ecology seeks to explain the number and relative abundance of
      coexisting species. Four research frontiers in community ecology are closely tied
      to research in systematics and taxonomy: the statistics of species richness
      estimators, global patterns of biodiversity, the influence of global climate
      change on community structure, and phylogenetic influences on community
      structure. The most pressing needs for taxonomic information in community ecology
      research are usable taxonomic keys, current nomenclature, species occurrence
      records and resolved phylogenies. These products can best be obtained from
      Internet-based phylogenetic and taxonomic resources, but the lack of trained
      professional systematists and taxonomists threatens this effort. Community
      ecologists will benefit most directly from research in systematics and taxonomy
      by making better use of resources in museums and herbaria, and by actively
      seeking training, information and collaborations with taxonomic specialists.

PMID- 15253347
TI  - Protist taxonomy: an ecological perspective.
AB  - This is an exploration of contemporary protist taxonomy within an ecological
      perspective. As it currently stands, the 'morphospecies' does not accommodate the
      information that might support a truly ecological species concept for the
      protists. But the 'morphospecies' is merely a first step in erecting a taxonomy
      of the protists, and it is expected to become more meaningful in the light of
      genetic, physiological and ecological research in the near future. One possible
      way forward lies in the recognition that sexual and asexual protists may all be
      subject to forces of cohesion that result in (DNA) sequence-similarity clusters.
      A starting point would then be the detection of 'ecotypes'--where genotypic and
      phenotypic clusters correspond; but for that we need better information regarding
      the extent of clonality in protists, and better characterization of ecological
      niches and their boundaries. There is some progress with respect to the latter.
      Using the example of a community of ciliated protozoa living in the stratified
      water column of a freshwater pond, it is shown to be possible to gauge the
      potential of protists to partition their local environment into ecological
      niches. Around 40 morphospecies can coexist in the superimposed water layers,
      which presumably represent different ecological niches, but we have yet to
      discover if these are discrete or continuously variable. It is a myth that
      taxonomic problems are more severe for protists than for animals and plants. Most
      of the fundamental problems associated with species concepts (e.g. asexuals,
      sibling species, phenotypic variation) are distributed across biota in general.
      The recent history of the status of Pfiesteria provides a model example of an
      integrated approach to solving what are essentially taxonomic problems.

PMID- 15253348
TI  - Stability or stasis in the names of organisms: the evolving codes of
      nomenclature.
AB  - Nomenclature, far from being a dry dusty subject, is today more relevant than
      ever before. Researchers into genomics are discovering again the need for systems
      of nomenclature-names are what we use to communicate about organisms, and by
      extension the rest of their biology. Here, we briefly outline the history of the
      published international codes of nomenclature, tracing them from the time of
      Linnaeus in the eighteenth century to the present day. We then outline some of
      what we feel are the major challenges that face the codes in the twenty-first
      century; focusing primarily on publication, priority, typification and the role
      of science in the naming of organisms. We conclude that the codes are essential
      for taxonomists in the pursuance of their science, and that the democratic nature
      of decision-making in the regulation of the rules of nomenclature, though
      sometimes perceived as a potential weakness, is in fact one of its great
      strengths.

PMID- 15253349
TI  - Prokaryote diversity and taxonomy: current status and future challenges.
AB  - The prokaryotes are by far the most abundant organisms inhabiting planet Earth.
      They are also by far the most diverse, both metabolically and phylogenetically;
      they encompass the Bacteria and the Archaea, two out of the three major divisions
      of living organisms. The current prokaryote species classification is based on a
      combination of genomic and phenotypic properties. The recommended cut-off value
      of 70% DNA-DNA similarity to delineate species signifies an extremely broad
      species definition for the prokaryotes compared with the higher eukaryotes. The
      number of validly named species of prokaryotes is currently slightly more than
      6200. However, on the basis of small-subunit rDNA characterization of whole
      communities and other approaches, the more exact number of species present can be
      inferred to be at least two orders of magnitude larger. Classic culturing methods
      based on colony formation on agar are generally unsatisfactory for the recovery
      of bacteria from the environment. Many of the most abundant prokaryotes in nature
      have not yet been brought into culture. Some of these may thrive by means of as
      yet unknown modes of energy generation. Several novel methods have recently
      enabled the isolation of some interesting organisms of environmental
      significance. A better coverage of the prokaryote diversity on Earth depends on
      such innovative approaches, combined with appropriate funding.

PMID- 15253350
TI  - Taxonomy and fossils: a critical appraisal.
AB  - Many compendia at the species, genus and family levels document the fossil
      record, but these are not standardized, nor usually critical in content, and few
      are available on the World Wide Web. The sampling of the available record is good
      for organisms with fossilizable parts, but preservational constraints on the
      entire morphology, life history and geographical distribution lead to
      difficulties in recognizing and naming species. We recommend abandoning some of
      the palaeontological species concepts such as chronospecies and stratospecies,
      and we advocate species recognition based on unique combinations of characters.
      The compilation of species lists is extremely time consuming, and given the
      inherent problems we suggest that compilation of generic lists is a more
      achievable goal because genera are recognized by definitive morphological
      characters. In calculating taxon duration, care must be taken to distinguish
      between mono-, para- and polyphyletic groups, the first being the only reliable
      unit for use in calculating diversity curves. We support the inclusion of fossils
      into classifications based on Recent organisms, but we recognize some of the
      problems this may pose for standard Linnaean classifications. Web-based taxonomy
      is the way forward, having the advantages of speed and currency of information
      dissemination, universal access with links to primary literature and increasingly
      sophisticated imagery. These advantages over conventional outlets will only be
      realized with careful Web design and a commitment to maintenance.

PMID- 15253351
TI  - Automated species identification: why not?
AB  - Where possible, automation has been a common response of humankind to many
      activities that have to be repeated numerous times. The routine identification of
      specimens of previously described species has many of the characteristics of
      other activities that have been automated, and poses a major constraint on
      studies in many areas of both pure and applied biology. In this paper, we
      consider some of the reasons why automated species identification has not become
      widely employed, and whether it is a realistic option, addressing the notions
      that it is too difficult, too threatening, too different or too costly. Although
      recognizing that there are some very real technical obstacles yet to be overcome,
      we argue that progress in the development of automated species identification is
      extremely encouraging that such an approach has the potential to make a valuable
      contribution to reducing the burden of routine identifications. Vision and
      enterprise are perhaps more limiting at present than practical constraints on
      what might possibly be achieved.

PMID- 15253353
TI  - Towards a working list of all known plant species.
AB  - A complete listing of the world's known plant species has long been considered
      desirable but has remained an elusive target for generations of botanists. The
      adoption of the Global Strategy for Plant Conservation has reinforced the urgent
      need for a global plant checklist to support, facilitate and monitor the
      conservation and sustainable use of plant diversity worldwide. The increasing
      availability of large databases of biological information over the Internet has
      demonstrated that many of the obstacles to the collation and dissemination of
      vast, shared datasets can be overcome. We examine the challenges that still
      remain to be addressed if the botanical community is to achieve its ambitious
      objective of delivering a working list of all known plant species by 2010.

PMID- 15253352
TI  - The promise of a DNA taxonomy.
AB  - Not only is the number of described species a very small proportion of the
      estimated extant number of taxa, but it also appears that all concepts of the
      extent and boundaries of 'species' fail in many cases. Using conserved molecular
      sequences it is possible to define and diagnose molecular operational taxonomic
      units (MOTU) that have a similar extent to traditional 'species'. Use of a MOTU
      system not only allows the rapid and effective identification of most taxa,
      including those not encountered before, but also allows investigation of the
      evolution of patterns of diversity. A MOTU approach is not without problems,
      particularly in the area of deciding what level of molecular difference defines a
      biologically relevant taxon, but has many benefits. Molecular data are extremely
      well suited to re-analysis and meta-analysis, and data from multiple independent
      studies can be readily collated and investigated by using new parameters and
      assumptions. Previous molecular taxonomic efforts have focused narrowly. Advances
      in high-throughput sequencing methodologies, however, place the idea of a
      universal, multi-locus molecular barcoding system in the realm of the possible.

PMID- 15253354
TI  - Biodiversity informatics: managing and applying primary biodiversity data.
AB  - Recently, advances in information technology and an increased willingness to
      share primary biodiversity data are enabling unprecedented access to it. By
      combining presences of species data with electronic cartography via a number of
      algorithms, estimating niches of species and their areas of distribution becomes
      feasible at resolutions one to three orders of magnitude higher than it was
      possible a few years ago. Some examples of the power of that technique are
      presented. For the method to work, limitations such as lack of high-quality
      taxonomic determination, precise georeferencing of the data and availability of
      high-quality and updated taxonomic treatments of the groups must be overcome.
      These are discussed, together with comments on the potential of these
      biodiversity informatics techniques not only for fundamental studies but also as
      a way for developing countries to apply state of the art bioinformatic methods
      and large quantities of data, in practical ways, to tackle issues of biodiversity
      management.

PMID- 15253355
TI  - Unitary or unified taxonomy?
AB  - Taxonomic data form a substantial, but scattered, resource. The alternative to
      such a fragmented system is a 'unitary' one of preferred, consensual
      classifications. For effective access and distribution the (Web) revision for a
      given taxon would be established at a single Internet site. Although all the
      international codes of nomenclature currently preclude the Internet as a valid
      medium of publication, elements of unitary taxonomy (UT) still exist in the paper
      system. Much taxonomy, unitary or not, already resides on the Web. Arguments for
      and against adopting a unitary approach are considered and a resolution is
      attempted. Rendering taxonomy essentially Web-based is as inevitable as it is
      desirable. Apparently antithetical to the UT proposal is the view that in reality
      multiple classifications of the same taxon exist, since different taxonomists
      often hold different concepts of their taxa: a single name may apply to many
      different (frequently overlapping) circumscriptions and more than one name to a
      single taxon. However, novel means are being developed on single Internet sites
      to retain the diversity of multiple concepts for taxa, providing hope that
      taxonomy may become established as a Web-based information discipline that will
      unify the discipline and facilitate data access.

PMID- 15253356
TI  - The role of taxonomy in species conservation.
AB  - Taxonomy and species conservation are often assumed to be completely
      interdependent activities. However, a shortage of taxonomic information and
      skills, and confusion over where the limits to 'species' should be set, both
      cause problems for conservationists. There is no simple solution because species
      lists used for conservation planning (e.g. threatened species, species richness
      estimates, species covered by legislation) are often also used to determine which
      units should be the focus of conservation actions; this despite the fact that the
      two processes have such different goals and information needs. Species
      conservation needs two kinds of taxonomic solution: (i) a set of practical rules
      to standardize the species units included on lists; and (ii) an approach to the
      units chosen for conservation recovery planning which recognizes the dynamic
      nature of natural systems and the differences from the units in listing processes
      that result. These solutions are well within our grasp but require a new kind of
      collaboration among conservation biologists, taxonomists and legislators, as well
      as an increased resource of taxonomists with relevant and high-quality skills.

PMID- 15253357
TI  - Taxonomy and environmental policy.
AB  - In 1992, with the United Nations Conference on Environment and Development in Rio
      de Janeiro and the subsequent Convention on Biological Diversity (CBD), the world
      changed for the science of taxonomy. Many taxonomists appear not to have noticed
      this change, but it has significantly altered the political climate in which
      taxonomic research is undertaken. By the late 1990s it was clear that effective
      implementation of the CBD needed the participation of and funding for the
      taxonomic community. In this paper, I chart the rise of the Global Taxonomy
      Initiative (GTI), review some of its goals and explore how it interacts with the
      CBD. The interactions of the GTI with the Global Environment Facility, a
      potential funding body, are explored, as are the possible synergies between the
      GTI and the many other global initiatives linking to taxonomy. Finally, I explore
      some of the challenges ahead as taxonomy begins to take a front seat in the
      implementation of environmental policy on the world stage.

PMID- 15253358
TI  - Taxonomy: where are we now?

PMID- 15253359
TI  - Now is the time.

PMID- 15253360
TI  - Tomorrow's taxonomy: collecting new species in the field will remain the rate
      limiting step.

PMID- 15253361
TI  - Documenting plant diversity: unfinished business.

PMID- 15253362
TI  - Taxonomy as a fundamental discipline.

PMID- 15253363
TI  - On the development and comparative evaluation of an ultrasound B-mode probe
      calibration method.
AB  - OBJECTIVE: Precise transducer calibration is an essential prerequisite for
      reliable surface registration based on ultrasound B-mode imaging devices. The
      clinical usage of a novel B-mode transducer calibration technique was evaluated
      and its attainable calibration precision assessed. MATERIALS AND METHODS: The
      Three Wire Method and the Cambridge Calibration Method were used as reference
      techniques to compare the efficiency, calibration precision and spatial
      requirements of the different techniques. A total of 20 calibration trials were
      performed using each technique and were statistically evaluated for accuracy and
      speed. RESULTS: The mean error characterizing the calibration precision of the
      Three Wire Method was 3.2 mm, obtained in a phantom with a volume of 14 x 10(6)
      mm(3) in 18.48 min. The Cambridge method resulted in a mean calibration error of
      2.2 mm, but required a larger phantom with a volume of 35 x 10(6) mm3 to be used
      for a duration of 9.30 min. The proposed method yielded an average calibration
      error of 1.9 mm and was performed, on average, in 2 min using a phantom with a
      size smaller than 1 x 10(6) mm3. CONCLUSIONS: The suggested calibration method
      offers decreased time and space while retaining an equivalent calibration
      precision when compared to established reference methods.

PMID- 15253364
TI  - A transcutaneous bone digitizer for minimally invasive registration in
      orthopedics: a real-time focused ultrasound beam approach.
AB  - Computer-guided navigation of surgical tool position in computer-assisted
      orthopedic systems requires the registration of computer tomographic (CT) images
      with underlying bone. This process is presently performed by manually digitizing
      points on bone with a pointer and aligning them to a preoperative CT scan. We
      propose the use of ultrasound to obtain points on bone transcutaneously. A custom
      made A-mode probe features a modular lens focusing system and a one-step
      calibration method. A stable and precise echo detection algorithm is also
      implemented. The accuracies of three signal detection algorithms--standard
      deviation, cross-correlation (XCORR) and short-time Fourier transform--were
      compared using a known reflected signal. XCORR showed the most accurate and
      stable operation. To test our method of obtaining bone surface points, a plastic
      model of the fourth human lumbar vertebra was CT scanned and then immersed in a
      water bath. Six surface registrations of the vertebra using an accurate pointing
      device were compared to ten registrations obtained using the US probe (using the
      XCORR algorithm). Student's T-test showed no significant difference in error
      between the two methods, proving that ultrasound registration, using our method,
      is equivalent to the more conventional pointer method.

PMID- 15253365
TI  - Preserving the abductor mechanism in robotic THR: the influence of stem design
      and cutterpath.
AB  - OBJECTIVE: The tip of the greater trochanter is the attachment site for the
      abductor muscles of the hip joint. Its preservation in robotic and conventional
      THR is important for normal gait. The effect of different stem designs and
      robotic cutterpaths on the preservation of the trochanter tip is examined.
      MATERIALS AND METHODS: One anatomical stem, one straight stem, and one stem
      specifically designed for robotic THR were implanted virtually in CT scans of
      osteoarthrotic hip joints using the Torch preoperative planning unit (URS-ortho).
      In transverse sections of the trochanter tip, dimensions of the trochanter area
      removed by the milling tool were recorded for each stem design and different
      cutterpaths (3-axis versus 5-axis milling). RESULTS: Five-axis milling showed
      significantly better results than 3-axis milling. For straight stems, more bone
      was removed than for anatomic stems. The most favorable results were achieved
      with 5-axis milling and a curved stem specifically designed for robotic THR.
      CONCLUSIONS: The introduction of 5-axis milling in robotic THR is an improvement
      of the technique and makes preservation of the abductor mechanism at the tip of
      the greater trochanter easier for the surgeon.

PMID- 15253366
TI  - Geometric accuracy in robot-assisted total hip replacement surgery.
AB  - OBJECTIVE: Robot-Assisted Surgery in Total Hip Replacement (RAS-THR) has become a
      fairly widespread procedure for hip replacement surgery in Europe. However, data
      on the geometric accuracy of the overall process have so far been unavailable.
      The equipment manufacturers have only published data on the accuracy of certain
      elements of the procedure (e.g., the accuracy of the robot system). This study
      aimed to investigate the overall geometric accuracy of the complete process of
      RAS-THR, as well as the influence of some of the individual component steps.
      MATERIALS AND METHODS: An anthropomorphic phantom has been developed representing
      the hip and upper leg region of a human body. The entire RAS-THR procedure can be
      carried out using this phantom. Studies were conducted to investigate the overall
      accuracy of the process, as well as the influence of some individual steps in the
      procedure, using both the ROBODOC and CASPAR systems. RESULTS: Overall geometric
      accuracy of the RAS-THR process was found to be within a standard deviation of
      0.5 mm and 0.3 degrees in the critical directions. Most individual steps in the
      process make similar contributions to the overall variation. The two robot
      systems examined offer comparable accuracy. CONCLUSION: Initial results seem to
      indicate that the RAS-THR process is acceptably accurate. However, acceptance
      criteria for the necessary geometric accuracy have not yet been defined.

PMID- 15253367
TI  - The use of rapid prototyping in the preoperative planning of distraction
      osteogenesis of the cranio-maxillofacial skeleton.
AB  - OBJECTIVE: In cranio-maxillofacial surgery, the principle of distraction
      osteogenesis (DO) can be used for the reconstruction of the deformed skull,
      midface complex, mandible and alveolar ridge. Optimal results can only be
      obtained with accurate planning of the osteotomies and accurate positioning of
      the distraction device. In addition, the surgical planning must be transferred
      very precisely to the patient in the operating theater. The clinical accuracy and
      utility of stereolithographic models in cranio-maxillofacial distraction
      osteogenesis of the midface, mandible and alveolar ridge will be demonstrated.
      MATERIALS AND METHODS: Thirteen patients were treated by DO in the cranio
      maxillofacial skeleton. Five patients suffered from midface retrusion and were
      treated by a LeFort III advancement. One patient suffered from an aseptic
      necrosis of the condylar process of the mandible and had a reconstruction of the
      condylar process by DO. Seven patients underwent an osteotomy of the alveolar
      ridge of the mandible with subsequent placement of distraction screws and
      implants because of advanced atrophy of the mandible. Following preoperative
      acquisition and conversion of the CT-scan data, a model was fabricated by
      stereolithography (SLA). Simulation of the osteotomies and placement of
      distraction devices was performed on these models, then surgical guides were used
      to transfer the surgical planning to the patient in the operating theater. Pre-
      and postoperative facial photographs and X-rays were compared to evaluate the
      accuracy of the transfer procedure. RESULTS: In all cases, matching of pre- and
      postoperative facial photographs and X-rays showed reconstruction of the bony
      structures to be as accurate as planned on the SLA models. Transfer of the
      surgical plan by means of custom-made surgical guides was optimal in all cases.
      CONCLUSION: Preoperative planning of distraction osteogenesis of the cranio
      maxillofacial skeleton and transfer to the operating theater by custom-made
      surgical guides remains the standard procedure for the planning of complex
      distraction cases. However, improvements in surgical simulation software and
      accurate virtual-reality surgery will probably make the use of these models
      redundant in the future.

PMID- 15253368
TI  - ACU professional health and wellness initiative.

PMID- 15253369
TI  - The limitation of good intentions: prescribing medications for the uninsured.
AB  - Identifying affordable drug therapy options for individuals who lack prescription
      drug insurance is a problem frequently encountered by prescribers. Medication
      samples and manufacturer-sponsored assistance programs represent sources often
      used to address affordability issues. However, these sources have the potential
      to introduce health disparities through various mechanisms, including reduced
      access to the drug of choice, consistencies with access, and drug regimen
      complexities that adversely affect adherence. Prescribers should consider all
      sources of affordable medications and openly discuss treatment options and the
      anticipated outcomes of each with patients to ensure the prescribing of agents
      that optimize outcomes while balancing patient affordability.

PMID- 15253370
TI  - Nationwide survey of dentist recruitment and salaries in community health
      centers.
AB  - Recruitment of dentists continues to be a problem in community health center
      (CHC) dental practices. This study was carried out to quantify the scope of the
      problem and to determine CHC dentist salaries and benefits. Community health
      center executive directors nationwide were surveyed regarding dentist vacancies,
      recruiting issues, and salary and benefit information. Of 345 surveys mailed, 159
      responses were received (46.1%). Slightly fewer than half of the responding
      executive directors (47.8%) reported one vacant dentist position. An additional
      11.9% of executive directors reported a second vacancy. The overall vacancy rate
      was 17.6%. Median salaries ranged from 78,000 dollars for entry-level dentists to
      90,000 dollars for dentists with 10 or more years of experience, not including
      benefits. There are difficulties in recruiting dentists to CHC dental practices.
      Mean salaries in CHCs are slightly higher than in academic positions, but less
      than in private practice employment or ownership. Caution should be used when
      comparing salaried positions with substantial benefits to self-employment or sole
      proprietorships.

PMID- 15253371
TI  - Access to hepatitis B vaccination among Korean American children in immigrant
      families.
AB  - This study examined social determinants affecting successful completion of the
      hepatitis B vaccination protocol among Korean American children in immigrant
      families. The effects of family characteristics, social support from support
      network, barriers to immunizations, and health beliefs concerning hepatitis B
      vaccination were examined using logistic regression analysis. Information support
      concerning parenting and child health (adjusted odds ratio [aOR] 2.55, 95%
      confidence interval [CI] 1.11-7.02) and perception that hepatitis B was a
      difficult disease from which to recover (aOR 2.11, 95% CI 1.20-3.72) appear to be
      the most important factors for vaccination compliance after adjusting for family
      income, mother's education level, and health insurance coverage. The burden of
      paying for immunizations (aOR 0.50, 95% CI 0.22-0.90) also had an impact on the
      vaccination status. These findings suggest that identifying the children at risk
      of undervaccination against hepatitis B maybe aided by focusing on these social
      determinants in addition to provider and sociodemographic characteristics.

PMID- 15253372
TI  - Chronic abdominal complaints and Helicobacter pylori in a Haitian population.
AB  - The objective of this study was to examine demographic, clinical, and pathologic
      variables, including Helicobacter pylori infection and malignancy, associated
      with chronic abdominal pain in a rural Haitian population. One hundred four
      patients underwent esophagogastroduodenoscopy, with biopsy only in those with
      gross findings. Associations between demographic, clinical, and pathologic
      variables were examined using the chi-square test. P values less than or equal to
      0.05 were considered statistically significant. The majority (n = 66; 63%)
      required biopsy. Of these, 62% were positive for H. pylori. The associations
      between (1) chest complaints and esophageal disease, (2) female gender and benign
      esophageal disease, and (3) chronic active gastritis and presence of H. pylori
      were significant. There was one malignancy. H. pylori gastritis was common;
      malignancy was rare. Demographic and clinical variables poorly predicted
      pathologic diagnosis, which is consistent with previous studies. Further study is
      needed to assess the influence of other variables, including the African enigma,
      on disease progression in this population.

PMID- 15253373
TI  - Can Community Health Center funding enhance health services for Native American
      tribes and organizations?
AB  - This paper reports on the applicability of the Public Health Service Act (42 USC,
      254b) Section 330 Community Health Center program to Arizona Native American
      tribes and organizations. Data review and analysis consisted of a review of two
      federal government documents concerning the funding of Community Health Center
      applications and a review of questionnaire responses received from the Arizona
      Native American health care community. Findings indicate a general lack of
      knowledge among the Arizona Native American health care community about the
      program as well as a need for capacity building among Arizona Native American
      tribes and organizations. As currently designed, the program has built-in
      barriers that prevent Native American tribes and organizations from applying for
      funding. Changes must be made to the existing program and local-level seminars
      must be offered to make this program and funding more readily available to
      Arizona Native American tribes and organizations.

PMID- 15253374
TI  - Low-income women's use of substance abuse and mental health services.
AB  - This paper examines the utilization of mental health, alcohol, and drug treatment
      in a sample of low-income women. We analyze data from the Women's Employments
      Study, a study examining the barriers to employment for welfare recipients, and
      compare prevalence rates of mental health disorders and service utilization with
      the National Comorbidity Survey. Fewer than one in five of the respondents with a
      current mental health and/or substance dependence problem in the Women's
      Employment Study (WES) received treatment in the past 12 months. A logistic
      regression model of the association among demographic variables, risk factors,
      and service utilization in the WES found that having a co-occurring substance
      dependence and mental health disorder was significantly associated with receiving
      treatment. Those respondents with an increased number of barriers were
      significantly less likely to receive treatment. The authors argue that the
      success of welfare reform may hinge on low-income women's access to and
      utilization of appropriate services.

PMID- 15253375
TI  - Influenza vaccination by race among disabled community dwelling older women.
AB  - Disabled older adults have been shown to be at risk for underutilization of some
      preventive services relative to able-bodied individuals. The Women's Health and
      Aging Study surveyed female Medicare enrollees in Baltimore, Maryland, who were
      among the most disabled community-dwelling women at the start of the study.
      Longitudinal survey data from the study were used to test for the existence or
      emergence of racial variation in influenza vaccination rates, for which racial
      variation has been shown in the general population. The primary analysis, using
      data on the same women before and after Medicare flu shot coverage began,
      suggested that influenza vaccination rates increased after Medicare coverage
      began and that there was no difference by race. A secondary analysis using data
      on women who were interviewed only after Medicare flu shot coverage began showed
      some racial variation, although the difference may have been larger prior to
      coverage. The utilization rate did not approach the Healthy People 2010 target.

PMID- 15253376
TI  - Promoting accountability: hospital charity care in California, Washington state,
      and Texas.
AB  - Debate as to whether private hospitals meet their charitable obligations is
      heated. This study examines how alternative state approaches for ensuring
      hospital accountability to the community affects charitable expenditures and
      potentially affects access to care for the uninsured. Descriptive and
      multivariate analyses were used to compare private California hospitals' charity
      care expenditures with those of hospitals in Texas and Washington state. The key
      finding from this study is that net of hospital characteristics, market
      characteristics and community need, Texas hospitals were estimated to provide
      over 3 times more charity care and Washington hospitals were estimated to provide
      66% more charity care than California hospitals. This finding suggests that more
      prescriptive community benefit or charity care requirements may be necessary to
      ensure that private hospitals assume a larger role in the care of the uninsured.

PMID- 15253377
TI  - Do characteristics associated with nursing home residents vary by race/ethnicity?
AB  - This study identifies differences in the predisposing, enabling, and need
      characteristics of racial/ethnic minorities and non-Hispanic white men and women
      upon nursing home admission. The data come from the 1999 National Nursing Home
      Survey of Current Residents and contain 3,798 women of color, 3,787 men of color,
      18,719 non-Hispanic white men, and 36,900 non-Hispanic white women. We estimated
      prevalence differences and 95% confidence intervals for the absolute differences
      in prevalence. Women of color in nursing homes are more likely than non-Hispanic
      white women in nursing homes to be bedfast and require assistance with dressing
      and money management. Men of color in nursing homes are more likely than non
      Hispanic white men in nursing homes to require assistance with eating, care of
      possessions, managing money, securing personal items, and using the telephone.
      The overall finding suggests that people of color in nursing homes have greater
      impairments than non-Hispanic whites in nursing homes, and that men of color in
      nursing homes have greater impairment than any other race or gender categories.

PMID- 15253378
TI  - The impact of acculturation on smoking in Asian American homes.
AB  - This study examined the relationship between acculturation and smoking in Asian
      American homes and the factors that predict whether Asian Americans have family
      members or visitors smoking in the home. A sample of 1,374 participants was
      selected using a stratified-cluster proportional sampling technique. Overall,
      38.3% were exposed to secondhand smoke in their home and 33.7% allowed smoking by
      visitors. Vietnamese had the significantly highest rates of smoking in the home
      (44.9%), followed by Cambodians (43.8%), Koreans (42.0%), and Chinese (29.7%).
      The independent variables that predicted smoking in the home were living in the
      United States five or fewer years, less acculturation, being female, being
      foreign born, having a family size of four or more, being Korean, Vietnamese, or
      Cambodian, and being smokers. The same variables predicted allowing visitors to
      smoke in the home, excluding being female. Protective factors included being more
      educated, being older, and having children under 18 at home.

PMID- 15253379
TI  - Colorectal cancer screening among a sample of community health center attendees.
AB  - To determine the rate of colorectal cancer screening in patients attending a
      sample of community health centers, medical records of 1,176 patients from eight
      community health centers were abstracted. Among the patients studied, 43.8% of
      patients had undergone at least one of the three colorectal screening tests
      (fecal occult blood test, colonoscopy, or flexible sigmoidoscopy) in the
      recommended interval. Colorectal screening in this community health center
      population was predicted by male gender, being African American, older age,
      having a greater number of chronic illnesses, a family history of colorectal
      cancer, and by having engaged in other preventive cancer screenings in the
      previous year. Although screening rates certainly were not optimal, they compare
      favorably to rates reported in national surveys for the general population. Our
      results add to a growing body of evidence that community health centers, despite
      serving disadvantaged populations, are able to deliver preventive care at rates
      comparable to health facilities used by the general population.

PMID- 15253380
TI  - An exploration of patients' trust in physicians in training.
AB  - Several characteristics associated with patient trust are identified. To
      determine the level of trust patients from disadvantaged circumstances have in
      their primary care resident physician, and to determine patient and physician
      characteristics that predict trust, we administered a survey to randomly selected
      primary care patients of an academic medical center staffed by internal medicine
      residents after a visit to their primary care provider. Participants were adults.
      The group was racially diverse (50% non-white), English-speaking, and from lower
      socioeconomic groups. The 10-page survey consisted of 7 sections (Physician Trust
      Scale, Patient Demographics, Patient Health and Well-Being, Patient-Physician
      Relationship Characteristics, Global Doctor Trust Scale, and Physician
      Characteristics). The average trust score for primary care providers was 42.70
      (standard deviation [SD] 6.20, maximum possible 50). Patient trust was associated
      with female gender of the participant, higher education level, male physician,
      and gender concordance between physician and patient, and was inversely related
      to patient age. Trust in the doctors and nurses at the hospital in which the
      clinic was located also had a positive association with trust. These patients
      from lower socioeconomic groups had relatively high levels of trust compared with
      patients from higher socioeconomic groups discussed in the literature.

PMID- 15253381
TI  - FLT3: receptor and ligand.
AB  - FLT3 is a receptor tyrosine kinase (RTK) expressed by immature hematopoietic
      progenitor cells. The ligand for FLT3 is a transmembrane or soluble protein and
      is expressed by a variety of cells including hematopoietic and marrow stromal
      cells; in combination with other growth factors, the ligand stimulates
      proliferation and development of stem cells, myeloid and lymphoid progenitor
      cells, dendritic cells and natural killer cells. Activation of the receptor leads
      to tyrosine phosphorylation of various key adaptor proteins known to be involved
      in different signal transduction pathways that control proliferation, survival
      and other processes in hematopoietic cells. FLT3 is not only of utmost interest
      regarding physiological processes of hematopoietic cells but also with regard to
      pathological aspects, namely leukemogenesis and diagnosis, prognosis and therapy
      of leukemia. Activating mutations of the receptor have been recognized as the
      most common genetic abnormality in acute myeloid leukemia (AML), occurring in
      about 30% of adult cases. AML patients with FLT3 mutations tend to have a poor
      prognosis, thus FLT3 is an attractive target of therapy, for instance using
      kinase inhibitors.

PMID- 15253382
TI  - New IL-6 (gp130) family cytokine members, CLC/NNT1/BSF3 and IL-27.

PMID- 15253384
TI  - Signalling by the type 1 insulin-like growth factor receptor: interplay with the
      epidermal growth factor receptor.
AB  - The type 1 insulin-like growth factor receptor (IGF-1R) plays an essential role
      in mammalian growth and development, and has emerged as a candidate therapeutic
      target in the treatment of cancer. While the pleiotropic cellular responses
      elicited following tyrosine phosphorylation of the IGF-1R is usually seen to
      involve the direct recruitment/activation of classical intracellular effector
      proteins, it is now clear that cross-talk between the IGF-1R and members of
      distinct receptor families also plays a significant role in effecting
      intracellular signalling. In recent years, a number of studies have highlighted
      the interaction(s) between the IGF-1R and the epidermal growth factor receptor
      (EGFR), another transmembrane tyrosine kinase that is an established cancer
      target. This review describes the components of the IGF signalling system and
      gives an overview of the emerging picture of the interrelationship that is now
      known to exist between the IGF and EGF receptors.

PMID- 15253383
TI  - Role of hepatocyte nuclear factors in growth hormone-regulated, sexually
      dimorphic expression of liver cytochromes P450.
AB  - The liver is a sexually dimorphic organ in many species, including humans. In
      rodent models, dramatic sex differences characterize the expression of numerous
      plasma proteins, receptors and other signaling molecules, and enzymes of steroid
      and foreign compound metabolism, including members of the cytochrome P450 (CYP)
      superfamily. The sexual dimorphism of liver gene expression is dictated by the
      temporal pattern of plasma growth hormone (GH) stimulation, which is intermittent
      and highly pulsatile in males and more frequent in females. Many liver-specific
      genes, including CYP genes, are regulated by the coordinated action of multiple
      hepatic nuclear factors (HNFs) through a complex transcriptional hierarchy. These
      HNFs are proposed to collaborate with the GH pulse-activated latent cytoplasmic
      transcription factor STAT5b to regulate the sex-dependent expression of liver
      CYPs. This hypothesis is supported by the finding that certain HNFs are regulated
      by GH and exhibit a differential responsiveness to the sex-specific pattern of GH
      secretion. In particular, recent studies of an HNF4alpha-deficient mouse model
      demonstrate an essential role for this nuclear receptor in regulating several
      liver-enriched transcription factors and sexually dimorphic CYPs in liver in
      vivo. Further studies on the mechanisms by which HNF4alpha and other liver
      factors respond to GH may expand our understanding of the mechanisms by which GH,
      via the coordinated action of HNFs and STAT5b, regulate sexually dimorphic liver
      gene expression.

PMID- 15253385
TI  - The effect of interleukin-16 and its precursor on T lymphocyte activation and
      growth.
AB  - Interleukin-16 (IL-16) was the first described T lymphocyte chemoattractant. It
      has since been shown that IL-16 also functions as a primer of T cell
      proliferation, a modulator of inflammatory and immune responses, a stimulus of B
      cell differentiation and an inhibitor of Human immunodeficiency virus (HIV)
      replication. Its precursor, Prointerleukin-16 (pro-IL-16), is expressed in both
      the nucleus and cytoplasm of T cells. Cytoplasmic pro-IL-16 serves as the
      precursor for mature IL-16 while nuclear pro-IL-16 is associated with G0/G1 cell
      cycle arrest. Herein, we review the ability of IL-16 to act as both primer and
      modulator of T lymphocyte growth. The impact of IL-16 on T cell apoptosis is also
      discussed. Finally, we describe the role of pro-IL-16 as a T lymphocyte cell
      cycle growth suppressor.

PMID- 15253386
TI  - Activin receptor signaling.
AB  - Activin is a member of the TGF-beta superfamily and has various effects on
      diverse biological systems. Activins initiate their cellular responses by binding
      to their receptors with intrinsic serine/threonine kinase activity and activation
      of specific downstream intracellular effectors termed Smad proteins. Smads relay
      the signal from the cell membrane to the nucleus, where they affect the
      transcription of target genes. Negative regulation of activin signal occurs at
      the extracellular, membrane, cytoplasmic and nuclear levels. The presence of many
      mechanisms for regulation shows its importance to normal physiology. Here, we
      review the latest advances in activin signal transduction.

PMID- 15253387
TI  - Recombinant hepatocyte growth factor accelerates cutaneous wound healing in a
      diabetic mouse model.
AB  - We examined effects of recombinant hepatocyte growth factor (HGF) on cutaneous
      wound healing, using a full-thickness cutaneous excision model in diabetic mice.
      Topical administration of HGF, as well as basic fibroblast growth factor (bFGF),
      promoted the rate of wound closure and re-epithelialization. Both HGF and bFGF
      enhanced expansion of the granulation tissue and stimulated neovascularization on
      day 7 postwounding, wherein the increase in microvessel density in HGF-treated
      wounds was higher than that in bFGF-treated wounds. Matrix metalloproteinases
      (MMP-2 and MMP-9) activities involved in cell migration, angiogenesis, and
      extracellular matrix (ECM) remodeling, were enhanced by HGF-treatment on day 7.
      On day 28 postwounding (later stages of wound healing), granulation tissue in
      bFGF-treated wounds remained to a greater extent than that seen in saline- and
      HGF-treated wounds. Likewise, bFGF- but not HGF-treatment stimulated DNA
      synthesis of fibroblasts in granulation tissue, suggesting that HGF stimulates
      wound healing with lesser degree of susceptibility to cutaneous scarring. We
      propose that supplement of HGF may be a potential therapeutic approach for
      treatment of cutaneous ulcer.

PMID- 15253388
TI  - On reassessment of the chicken TGFB4 gene as TGFB1.
AB  - Three TGFB isoforms, TGFB1-3, are present in mammalian cells. The presence of
      four TGFB isoforms has been reported in avian species, though the sequence of
      TGFB4 was not conclusively determined. Our previously published data show that
      TGFB4 is actually the chicken ortholog of TGFB1. We mapped TGFB1 but not TGFB4 to
      linkage group E25C31 on GGA32 next to RYR1 forming a conserved segment with human
      chromosome HSA19q13.1-q13.2 and, therefore, being definitely the ortholog of
      human TGFB1. We, therefore, suggest that what was once called chicken "TGFB4" is
      actually TGFB1. Thus, in the evolutionary lineages of birds and mammals there are
      only three TGFB isoforms.

PMID- 15253389
TI  - A study of relapse after MDT in a district in West Bengal, India.
AB  - A study was undertaken to estimate the magnitude of the problem of relapse and to
      identify factors responsible for relapse in leprosy units that were delivering
      MDT in Purulia District of West Bengal. From records patients were classified as
      "Relapse" or "Not relapse". "Not relapse" patients were selected by simple random
      sampling from the Surveillance Register and were matched according to age, sex,
      and the leprosy control unit. 128 cases ("Relapse") and 128 controls ("Not
      relapse") were interviewed in the clinic using a pre-tested questionnaire.
      Details of methods to identify and confirm relapse were circulated to all
      reporting units for ensuring uniformity and reliability. NGOs covered 42% of the
      population, while the State Government covered the remaining. The patients had
      been followed up after completion of treatment for a period of two years in PB
      leprosy and for five years in MB leprosy. The study revealed that the relapse
      rate was 1.71/1000 person-years for original PB cases and 0.76/1000 person-years
      for original MB cases. The study also showed that history of contact with an
      active leprosy patient and irregular treatment led more PB cases to relapse than
      control cases. All patients with an initial BI of 3+ relapsed with a BI of 1+ or
      2+.

PMID- 15253390
TI  - "Instant" new leprosy case-detection: an experience in Bihar State in India.
AB  - The National Leprosy Eradication Programme (NLEP) is based on survey, education
      and treatment, including coverage of all the registered cases with multi-drug
      therapy (MDT). The Government of India introduced MDT in all leprosy endemic
      districts through a vertical set-up, and through mobile leprosy treatment units
      in low endemic districts. Anti-leprosy work has not been uniform in all the
      states and needed push-start in some, such as Bihar. There have been spurts of
      leprosy elimination activities and the entire populations of the regions have not
      been covered because of various administrative reasons and logistic problems. In
      Singhbhum district of Bihar, a successful attempt was made to cover the maximum
      population by campaign approach. The strategy was to involve all the field
      workers of the leprosy programme in the district, supported by a small group of
      experienced personnel. The campaign, lasting for 39 working days, resulted in
      detecting leprosy cases equivalent to 64% of cases detected during the previous
      one full year. The entire operation helped the local staff to gain experience
      that would be useful for the future of the NLEP, and also provide an insight into
      working practices. Similar campaign approach can be used in situations where case
      detection activities are feeble and the implementation of MDT is slow. If such
      campaigns are repeated at appropriate intervals, it will be a great support to
      achieving the goal of leprosy elimination.

PMID- 15253391
TI  - Trends in detection of new leprosy cases at two centres in Himachal Pradesh,
      India: a ten-year study.
AB  - An impressive decline in leprosy prevalence rate (PR) in all endemic districts of
      India is seen in the post-MDT era. However, the new case-detection rate, an
      important statistical indicator in leprosy control programmes, has not shown
      significant decline in spite of all efforts. In Himachal Pradesh, a decline in PR
      from 7.8 to 0.56/10000 between 1991 to 2000 is seen, and recently the State has
      won national acclaim for having achieved the goal of elimination of leprosy in
      all the districts. The vertical leprosy programme has been integrated into
      general health services of the state. An analysis of data from 1991 to 2000 of
      two leprosy control units of Himachal Pradesh, the Urban Leprosy Clinic in Shimla
      (ULC-S) and the District Leprosy Control Unit in Mandi (DLCU-M), showed no
      significant decline in the new cases detected. 277 and 271 new cases were
      detected at these centres respectively; these included 2.2% and 1.5% children of
      less than 14 years of age. Almost 75% of these cases were males and of MB type. A
      steadily increasing trend in the annual detection of new cases was seen at both
      the centres during the decade. The cases registered at DLCU-M were mainly
      indigenous to the district. At ULC-S, 45 migrant cases from other endemic areas
      mainly from Nepal, Bihar, and Uttar Pradesh-had also contributed to the increased
      number of new cases. Other possible causes discussed for this higher new case
      detection, e.g. overdiagnosis, detection of backlog "hidden cases" and voluntary
      reporting of patients, do not differ from those seen in other parts of the
      country or the world.

PMID- 15253392
TI  - Study on integration of the National Leprosy Eradication Programme into primary
      health care services: a pilot project.
AB  - The Central Leprosy Training and Research Institute, Chengalpattu, Tamil Nadu,
      undertook an interventional study, as a pilot project, on integration of the
      National Leprosy Eradication Programme (NLEP) vertical activities into the PHC
      system in two selected districts of Visakhapatnam and Krishna of Andhra Pradesh,
      between September 1997 and March 1999. The objective of the study was to assess
      the various operational aspects and implications of integrated implementation of
      the activities of the NLEP through the PHC system. 1,304,163 people (239,142 in
      the study group and 1,065,020 in the control group) were enrolled in the study.
      The methodology employed in carrying out the pilot project in the two selected
      districts is described. MDT was in operation for more than 5 years in these two
      districts through vertical approach. Prevalence has declined from >50/10000 at
      the start of MDT to about 3/10000 at the start of the project. During the
      implementation phase, 1459 new leprosy cases were detected (NCDR 5.39/10000
      person-years) and 1458 cases were released from treatment (RFT rate: 93.04%) and
      towards the end of the project 450 cases were under treatment (PR 1.66/10000).
      Simple rates, ratios and proportions were used in the analysis of data and
      results were compared. The interventional study was designed to assess the
      implications and impact of implementation of NLEP activities through PHC staff.
      The study design, rationale, data collection, data processing, quality control
      methods employed in the study project and the results are discussed. The results
      of the study indicate that integrated implementation of the NLEP by PHC staff is
      feasible, if proper support is provided.

PMID- 15253393
TI  - People's perception of leprosy--a study in Delhi.
AB  - Leprosy is considered to cause more social than medical problems. The present
      study focussed on this aspect in order to investigate the level of awareness
      among people--about their attitude towards the disease and the afflicted. The
      results are based on interviews with 104 persons in Delhi. The sample data
      revealed that the level of knowledge of leprosy was inadequate. The cause of the
      disease was known to 44.2% of those interviewed, while 31.7% were completely
      ignorant; 6.7% believed it to be the consequence of an individual's past
      misdeeds, and 1.9% believed it to have been caused by divine curse. 63.1% were
      aware that the disease is curable. 73.1% of the persons interviewed sympathised
      with leprosy-afflicted beggars. 61.5% favoured leprosy patients to stay with
      their families and within their communities. 67.3% felt that the cured could
      marry, while 25% felt that the leprosy-afflicted should stay in leprosy colonies
      away from the society. 54.8% were reluctant to employ the leprosy-afflicted as
      domestic help, and 31.7% were reluctant to establish matrimonial relationship
      with a family having a leprosy-afflicted person. The data call for
      intensification ofpublic awareness regarding the aetiology of leprosy. Positive
      and scientific information should be disseminated to minimize the social
      prejudices associated with the disease.

PMID- 15253394
TI  - Childhood leprosy in eastern Nepal: a hospital-based study.
AB  - A hospital-based retrospective study on childhood leprosy was carried out at B.R.
      Koirala Institute of Health Sciences, Dharan, covering the period April 1998
      April 2002. 20 (4.45%) leprosy patients were detected in children aged 6-14
      years. The male:female ratio was 4:1. History of contact was found in 10% of the
      patients. The commonest type of leprosy was borderline tuberculoid leprosy
      (550%), followed by borderline lepromatous leprosy (301%). Most of the patients
      had more than one lesion. Nerve involvement and grade 2 deformity were noted in
      55% and 20% of the patients respectively. Slit skin smear was positive in 30% of
      patients.

PMID- 15253395
TI  - Molluscum contagiosum-like lesions in lepromatous leprosy.
AB  - A 23-year old male presented with multiple, asymptomatic, raised lesions of 4
      months' duration. The lesions were well demarcated. Dome-shaped papules and
      nodules were seen on normal looking skin; some were shiny, pearly white and
      umbilicated. Bilateral greater auricular, ulnar, radial cutaneous and lateral
      popliteal nerves were thickened. Slit skin smear from an umbilicated nodule had a
      BI of 6+. Biopsy showed features of lepromatous leprosy.

PMID- 15253396
TI  - Is open access to medical research literature relevant to low- and middle-income
      countries?

PMID- 15253397
TI  - Coeliac disease in Indian children.

PMID- 15253398
TI  - Human resources and infrastructure for eye care in India: current status.
AB  - BACKGROUND: An ophthalmic workforce and infrastructure planning survey was
      undertaken to provide a valid evidence base for human resource and infrastructure
      requirements for elimination of avoidable blindness. This is the first time that
      such an extensive survey has been done in India. METHODS: Pre-tested
      questionnaires were administered to all district-level blindness officials and
      ophthalmology training institutions during April 2002-March 2003. Supplementary
      data sources were used wherever necessary. Data analysis was done in Stata 8.0.
      Projections of the existing ophthalmologists and dedicated eye beds were made for
      the entire country using the mean, median and range for each individual state.
      RESULTS: The response rate was 89.3%. More than half the eye care facilities were
      located in the private sector. Sixty-nine per cent of the ophthalmologists were
      employed in the private and non-governmental sectors; 71.5% of all dedicated eye
      beds were managed by these two sectors. Five states (Maharashtra, Uttar Pradesh,
      Karnataka, Andhra Pradesh and Tamil Nadu) had half the practising
      ophthalmologists in India. There was a wide disparity in access to
      ophthalmologists and dedicated eye beds across the country. Using the median to
      obtain medium projections, it is estimated that there are 9478 practising
      ophthalmologists and 59 828 dedicated eye beds in India. CONCLUSIONS: India will
      be able to meet the requirements for trained ophthalmologists and dedicated eye
      beds to achieve the goals of Vision 2020. Some states will need special
      attention. Instead of an across-the-board increase in ophthalmologists and eye
      beds, regions which are deficient will need to be prioritized and concerted
      action initiated to achieve an equitable distribution of the available resources.

PMID- 15253400
TI  - Hereditary persistence of foetal haemoglobin in a tribal family of Orissa, India.
AB  - BACKGROUND: The hereditary persistence of foetal haemoglobin (HPFH) is an
      autosomal co-dominant, rare, inherited condition. It occurs due to failure of
      switching off of the production of gamma-chains during the neonatal period
      leading to a high level of foetal haemoglobin in adult life but without any
      anaemia. During screening a randomly selected Paraja Bhuyan tribal population for
      haemoglobinopathies in the Sundargarh district of western Orissa, HPFH was
      detected in a family. METHODS: Horizontal haemoglobin electrophoresis was carried
      out to identify abnormal haemoglobins and quantitation of the haemoglobin A2
      fraction was done by the elution method at pH 8.9. Haemoglobin F was estimated.
      Haematological parameters were studied using an automated blood cell counter. The
      acid elution-staining test was used to demonstrate the intracellular distribution
      of haemoglobin F-containing erythrocytes. RESULTS: Four members of the tribal
      family had a high level (6.5%-13.7%) of foetal haemoglobin--the mother and 3
      children. None of them had any apparent clinical or haematological abnormality
      except for mild pallor in the two younger children. The add elution-staining test
      revealed pancellular distribution of foetal haemoglobin in the erythrocytes of
      all the affected family members. CONCLUSION: Genetic traits such as hereditary
      persistence of foetal haemoglobin, although rare, are prevalent in India.

PMID- 15253399
TI  - Erythrocyte indices in pregnancy: effect of intermittent iron supplementation.
AB  - BACKGROUND: Erythrocyte indices change in pregnancy, mainly due to physiological
      haemodilution and iron-deficient erythropoiesis. The present study was undertaken
      to determine the haematological indices during different periods of gestation in
      women receiving daily iron supplements and compare them with those in women
      receiving weekly iron supplements. METHODS: Pregnant women < 20 weeks of
      gestation attending the antenatal clinic at the All India Institute of Medical
      Sciences were randomized to receive either 100 mg elemental iron daily or 200 mg
      elemental iron weekly. The haemoglobin, haematocrit, mean corpuscular volume,
      mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were
      estimated at baseline, after 1 month, 3 months and at 34 weeks of gestation.
      RESULTS: Changes consistent with physiological haemodilution in mid-term
      pregnancy were noted and the values at 34 weeks of gestation were not
      significantly different between the two groups. CONCLUSION: The effects of
      intermittent iron supplementation on the erythrocyte indices in pregnancy are
      comparable with those observed with daily supplementation.

PMID- 15253401
TI  - Madras pattern of motor neuron disease: improvement of symptoms with intravenous
      immunoglobulin.
AB  - A 13-year-old Chinese boy with features of the Madras pattern of motor neuron
      disease (MMND) presented to us. The benign focal atrophy of the extremities,
      especially the upper, and associated hearing impairment were important clues to
      the clinical diagnosis. A recent pathological report suggests that an
      inflammatory aetiology needs to be considered for this special type of motor
      neuron disease. Therefore, treatment with intravenous immunoglobulin 400 mg/kg
      once daily was administered for 5 days, and improvement of symptoms was noted at
      6 months of follow up.

PMID- 15253402
TI  - Management of rheumatoid arthritis.
AB  - The past few years have witnessed a major change in the approach to the treatment
      of rheumatoid arthritis. The present focus is on early recognition and prompt
      treatment with disease-modifying antirheumatic drugs of which methotrexate
      continues to be the drug of choice. Leflunomide is an important recent addition
      to the list of available drugs. The use of combinations of disease-modifying
      antirheumatic drugs is gaining wide acceptance. A better understanding of the
      pathobiology of rheumatoid arthritis has led to the development of targeted
      therapies such as tumour necrosis factor blockers. There are robust data to show
      the clinical utility of tumour necrosis factor blockers in patients with
      rheumatoid arthritis.

PMID- 15253403
TI  - A young man with generalized oedema, vomiting and easy fatiguability.

PMID- 15253404
TI  - Enhancing the evidence base for HIV/AIDS control in India.
AB  - An optimum evidence base is necessary for the effective control of HIV/AIDS in
      India, as the lack of an adequate evidence base on critical issues leads to
      controversy and hurdles. To assess the trends in the HIV/AIDS evidence base for
      India, a PubMed literature search for publications from India in 2002 and 2003 on
      HIV/AIDS was done, and abstracts from India in one major international HIV/AIDS
      conference in 2002, and presentations at one major HIV/AIDS conference in India
      in 2003 were reviewed. The PubMed search revealed 145 papers with abstracts on
      HIV/AIDS from India during this period, which was 1.4% of the worldwide HIV/AIDS
      publications. Of these 145 publications, 124 (85.5%) were based on original
      research and, of these, 27.4% were in the basic sciences, 62.9% in the clinical
      sciences, and 9.7% in the public health sciences; 53.2% of the original research
      papers were published in journals with impact factors ranging from 0 to 1. Many
      vital issues for HIV control, such as validation of the methods used to assess
      HIV burden in the population, large-scale impact assessment of HIV prevention
      programmes, cost-effectiveness of HIV interventions, and critical evidence-to
      policy issues, were not covered. Of the 8824 abstracts accepted for presentation
      at the XIV International AIDS Conference 2002 at Barcelona, 8% were from India--a
      fair representation given that India has about 10% of the world's HIV burden.
      However, the utility of this information is severely limited with the majority of
      it not getting translated into detailed papers in the peer-reviewed literature
      for widespread scrutiny and use. The views expressed by many experts at the
      Fourth International Conference on AIDS India 2003 at Chennai were impressive,
      but the presentation and discussion on original research data from India were
      sparse. From these various sources, it is estimated that the available evidence
      base for HIV/AIDS control in India is suboptimal. Using certain assumptions, it
      is estimated that to provide an adequate evidence base for the control of
      HIV/AIDS in India, quality original HIV/AIDS research in India would have to
      double in the basic and clinical sciences, and increase by more than 5 times for
      the public health sciences. Enhancingthis evidence base to an optimum level would
      require optimizing its demand, systematically planning its supply locally in
      India and creating an environment suitable for its development. To effectively
      control HIV/AIDS in India, strategic planning is needed to develop an evidence
      base that covers all critical areas where information is needed. Formation of a
      Society for HIV/AIDS Research in India by involving all the major stakeholders
      could help build up momentum towards establishing a comprehensive, relevant,
      dynamic and long-term evidence base that provides rigorous and timely information
      needed for HIV/AIDS control.

PMID- 15253405
TI  - Open access publishing: a digital bridge for developing nations?

PMID- 15253406
TI  - Killing the cadaver transplant programme.

PMID- 15253407
TI  - The good news regarding HIV.

PMID- 15253409
TI  - The economics of cancer treatment: implications for quality-of-life assessment in
      India.

PMID- 15253408
TI  - Computer use among postgraduates of a medical college in southern India.

PMID- 15253410
TI  - Microbes and the space programme.

PMID- 15253411
TI  - Six institutions to improve medical facilities!

PMID- 15253412
TI  - It is a matter of trust!

PMID- 15253413
TI  - Therapy for AIDS: affordable and accessible.

PMID- 15253414
TI  - 16O/18O labeling in the spotlight.

PMID- 15253415
TI  - Nuclear medicine in the era of genomics and proteomics: lessons from annexin V.
AB  - In the past decade, genomics and proteomics have begun to develop many new
      targets for potential diagnostic and therapeutic agents. Among the life sciences,
      nuclear medicine is also deeply involved in the field of clinical investigation.
      Experience with radiolabeled annexin V highlights the many steps required to
      translate a good basic-science concept into the clinical setting. This model also
      emphasizes the value of synergy between basic and medical specialties in
      developing and optimizing a clinically useful product initially derived from
      basic investigation.

PMID- 15253416
TI  - Quantification in proteomics through stable isotope coding: a review.
AB  - This review focuses on techniques for quantification and identification in
      proteomics by stable isotope coding. Methods are examined for analyzing
      expression, post-translational modifications, protein:protein interactions,
      single amino acid polymorphism, and absolute quantification. The bulk of the
      quantification literature in proteomics focuses on expression analysis, where a
      wide variety of methods targeting different features of proteins are described.
      Methods for the analysis of post-translational modification (PTM) focus primarily
      on phosphorylation and glycosylation, where quantification is achieved in two
      ways, either by substitution or tagging of the PTM with an isotopically coded
      derivatizing agent in a single process or by coding and selecting PTM modified
      peptides in separate operations. Absolute quantification has been achieved by age
      old internal standard methods, in which an isotopically labeled isoform of an
      analyte is synthesized and added to a mixture at a known concentration. One of
      the surprises is that isotope coding can be a valuable aid in the examination of
      intermolecular association of proteins through stimulus:response studies.
      Preliminary efforts to recognize single amino acid polymorphism are also
      described. The review ends with the conclusion that (1) isotope ratio analysis of
      protein concentration between samples does not necessarily relate directly to
      protein expression and rate of PTM and (2) that multiple new methods must be
      developed and applied simultaneously to make existing stable isotope
      quantification methods more meaningful. Although stable isotope coding is a
      powerful, wonderful new technique, multiple analytical issues must be solved for
      the technique to reach its full potential as a tool to study biological systems.

PMID- 15253417
TI  - Human serum proteins preseparated by electrophoresis or chromatography followed
      by tandem mass spectrometry.
AB  - Electrophoretic and chromatographic sample preparations were compared and
      together detected the presence of some 600 types of protein products in human
      serum. Proteins from crude serum preseparated by ionic electrophoresis,
      chromatography, or a combination of both were analyzed. Proteins were digested
      with trypsin or chymotrypsin. Naturally occurring peptides were also collected by
      reversed-phase chromatography. The resulting peptides were identified by tandem
      mass spectrometry. The peptides were either desorbed by a laser from a metal chip
      into a quadrupole-time-of-flight mass spectrometer or ionized as an electro-spray
      from reversed-phase chromatography via a metal needle under voltage into an ion
      trap mass spectrometer. All of the commonly known proteins associated with serum
      were detected, and the two mass spectrometers agreed on the identity of abundant
      serum proteins. Preseparation of serum proteins prior to digestion markedly
      enhanced the capacity to detect un-common proteins from blood. Electrophoretic-
      and chromatography-based experiments were found to be complementary. Many novel
      cellular proteins not previously associated with serum were recorded.

PMID- 15253418
TI  - Analysis of lectin-bound glycoproteins in snake venom from the Elapidae and
      Viperidae families.
AB  - This paper describes an efficient method of studying the glycoproteins found in
      snake venom. The glycosylation profiles of the Elapidae and Viperidae snake
      families were analyzed using FITC-labeled lectin glycoconjugates. The Con A
      agarose affinity enrichment technique was used to fractionate glycoproteins from
      the N. naja kaouthia venom. The results revealed a large number of Con A binding
      glycoproteins, most of which have moderate to high molecular weights. To identify
      the proteins, the isolated glycoprotein fractions were subjected to two
      dimensional electrophoresis and MALDI-TOF MS. Protein sequences were compared
      with published protein databases to determine for their biological functions.

PMID- 15253419
TI  - Using proteomics to mine genome sequences.
AB  - We present a method for mining unannotated or annotated genome sequences with
      proteomic data to identify open reading frames. The region of a genome coding for
      a protein sequence is identified by using information from the analysis of
      proteins and peptides with MALDI-TOF mass spectrometry. The raw genome sequence
      or any unassembled contigs of an organism are theoretically cleaved into a number
      of equal sized but overlapping fragments, and these are then translated in all
      six frames into a series of virtual proteins. Each virtual protein is then
      subjected to a theoretical enzymatic digestion. Standard proteomic sample
      preparation methods are used to separate, array, and digest the proteins of
      interest to peptides. The masses of the resulting peptides are measured using
      mass spectrometry and compared to the theoretical peptide masses of the virtual
      proteins. The region of the genome responsible for coding for a particular
      protein can then be identified when there are a large number of hits between
      peptides from the protein and peptides from the virtual protein. The method makes
      no assumptions about the location of a protein in a particular gene sequence or
      the positions or types of start and stop codons. To illustrate this approach, all
      773 proteins of Pseudomonas aeruginosa contained in SWISS-PROT were used to
      theoretically test the method and optimize parameters. Increasing the size of the
      virtual proteins results in an overall improvement in the ability to detect the
      coding region, at the cost of decreasing the sensitivity of the method for
      smaller proteins. Increasing the minimum number of matching peptides, lowering
      the mass error tolerance, or increasing the signal-to-noise ratio of the
      simulated mass spectrum, improves the ability to detect coding regions. The
      method is further demonstrated on experimental data from Mycobacterium
      tuberculosis and is also shown to work with eukaryotic organisms (e.g., Homo
      sapiens).

PMID- 15253420
TI  - Highly altered protein expression profile in the adriamycin resistant MCF-7 cell
      line.
AB  - The protein expression pattern in the cytosol fraction of the adriamycin
      resistant MCF-7 cell line (MCF-7/ADR) was compared to that of the parental MCF-7
      cell line using two-dimensional gel electrophoresis and mass spectrometry. Twenty
      proteins with altered abundances were identified and studied in MCF-7/ADR. Both
      up regulation and down regulation are characterized. The most striking
      differences were found for proteins that were uniquely expressed in this cell
      line and not detectable in the parental MCF-7 cell line. These proteins include
      annexin I, the neuronal ubiquitin carboxyl hydrolase isoenzyme L-1 (also known as
      PGP9.5), glutathione-S-transferase pi class, nicotinamide N-methyltransferase,
      and interleukin-18 precursor. On the other hand, catechol-O-methyltransferase was
      expressed in the parental cell line, but was not detected in the adriamycin
      resistant cell line. This protein expression pattern was unique to MCF-7/ADR and
      not observed in MCF-7 cell lines selected for resistant to etoposide,
      mitoxantrone or melphalan.

PMID- 15253421
TI  - Proteomic analysis of human tears: defensin expression after ocular surface
      surgery.
AB  - Human tear protein profiles were monitored by surface enhanced laser
      desorption/ionization-time-of-flight mass spectrometry ProteinChip technology
      (SELDI-TOF ProteinChip) and liquid chromatography-mass spectrometry (LC-MS).
      Tears were collected from 21 patients scheduled for surgery to remove an ocular
      surface neoplasm prior to surgery (day 0) and on days 1, 3, and 30
      postoperatively. Using this proteomic approach, we verified that three human
      alpha-defensins (HNP-1, HNP-2, and HNP-3) were significantly up-regulated in
      their expression after surgery and that their levels decreased to approximately
      normal by day 30 by which time healing was complete. Further confirmation of the
      identity of the alpha-defensins in human tears was made by LC purification,
      trypsin digestion, and ESI-MS/MS analysis of their tryptic digests. The
      concentrations of HNP-1 and HNP-2 were determined and shown to be markedly
      increased after ocular surface surgery. The results of the study suggest that
      human alpha-defensins HNP-1, HNP-2, and HNP-3 are up-regulated after surgery, and
      may in addition to their antimicrobial properties have an important role in wound
      healing.

PMID- 15253422
TI  - Toward a general chemical method for rapidly mapping multi-protein complexes.
AB  - Ru(II)(bpy2)32+Cl2, ammonium persulfate, and visible light irradiation has been
      shown to rapidly and efficiently cross-link several interacting proteins.
      However, this methodology has not yet been used to map the architecture of large
      multi-protein complexes. In this study, this chemistry is applied to the
      crystallographically characterized yeast proteasome. The data obtained
      demonstrate both the method's increased generality and fidelity in comparison to
      traditional bifunctional cross-linking reagents, while also highlighting the
      future need for developing better analytical techniques to separate cross-linked
      products.

PMID- 15253423
TI  - Identification of phosphorylation sites in protein kinase A substrates using
      artificial neural networks and mass spectrometry.
AB  - Protein phosphorylation plays a key role in cell regulation and identification of
      phosphorylation sites is important for understanding their functional
      significance. Here, we present an artificial neural network algorithm: NetPhosK
      (http://www.cbs.dtu.dk/services/NetPhosK/) that predicts protein kinase A (PKA)
      phosphorylation sites. The neural network was trained with a positive set of 258
      experimentally verified PKA phosphorylation sites. The predictions by NetPhosK
      were validated using four novel PKA substrates: Necdin, RFX5, En-2, and Wee 1.
      The four proteins were phosphorylated by PKA in vitro and 13 PKA phosphorylation
      sites were identified by mass spectrometry. NetPhosK was 100% sensitive and 41%
      specific in predicting PKA sites in the four proteins. These results demonstrate
      the potential of using integrated computational and experimental methods for
      detailed investigations of the phosphoproteome.

PMID- 15253424
TI  - Global analysis of the membrane subproteome of Pseudomonas aeruginosa using
      liquid chromatography-tandem mass spectrometry.
AB  - Pseudomonas aeruginosa is one of the most significant opportunistic bacterial
      pathogens in humans causing infections and premature death in patients with
      cystic fibrosis, AIDS, severe burns, organ transplants, or cancer. Liquid
      chromatography coupled online with tandem mass spectrometry was used for the
      large-scale proteomic analysis of the P. aeruginosa membrane subproteome.
      Concomitantly, an affinity labeling technique, using iodoacetyl-PEO biotin to tag
      cysteinyl-containing proteins, permitted the enrichment and detection of lower
      abundance membrane proteins. The application of these approaches resulted in the
      identification of 786 proteins. A total of 333 proteins (42%) had a minimum of
      one transmembrane domain (ranging from 1 to14) and 195 proteins were classified
      as hydrophobic based on their positive GRAVY values (ranging from 0.01 to 1.32).
      Key integral inner and outer membrane proteins involved in adaptation and
      antibiotic resistance were conclusively identified, including the detection of
      53% of all predicted opr-type porins (outer integral membrane proteins) and all
      the components of the mexA-mexB-oprM transmembrane protein complex. This work
      represents one of the most comprehensive proteomic analyses of the membrane
      subproteome of P. aeruginosa and for prokaryotes in general.

PMID- 15253425
TI  - Proteome analysis of lipid rafts in Jurkat cells characterizes a raft subset that
      is involved in NF-kappaB activation.
AB  - Lipid rafts are detergent-insoluble membrane domains that play a key role in
      signal transduction by the T-cell antigen receptor. Proteome analysis revealed
      the presence of amidosulfobetaine-soluble signal transducing, integral membrane,
      cytoskeletal, heat shock, and GTP-binding proteins in rafts prepared from Jurkat
      cells. Several of these proteins were recruited to rafts by CD3/CD28
      costimulation. Of particular interest is the inducible association of activated
      IkappaB kinase complexes with raft vesicles that could be captured with anti
      flotillin-1 antibodies. Following amidosulfobetaine solubilization, flotillin
      beta and IKKbeta underwent reciprocal co-immunoprecipitation. Treatment of Jurkat
      cells with methyl-beta-cyclodextrin disrupted the assembly and activation of this
      raft complex and also interfered in CD3/ CD28-induced activation of a NF-kappaB
      response element in the IL-2 promoter.

PMID- 15253426
TI  - Investigation of doxorubicin resistance in MCF-7 breast cancer cells using shot
      gun comparative proteomics with proteolytic 18O labeling.
AB  - A shot-gun comparative proteomic investigation utilizing proteolytic 18O labeling
      has been carried out on a drug susceptible MCF-7 human breast cancer cell line
      and a related cell line that is resistant to doxorubicin. The proteolytic 18O
      labeling method has been further refined and optimized for application to a
      protein fraction stemming from the cytosol of the breast cancer cells. The
      comparative investigation revealed several proteins with altered expression
      levels in the doxorubicin resistant line. These altered proteins are considered
      for a possible role in doxorubicin resistance.

PMID- 15253427
TI  - Sequential Peptide Affinity (SPA) system for the identification of mammalian and
      bacterial protein complexes.
AB  - A vector system is described that combines reliable, very low level, regulated
      protein expression in human cells with two affinity purification tags (Sequential
      Peptide Affinity, or SPA, system). By avoiding overproduction of the target
      protein, this system allows for the efficient purification of natural protein
      complexes and their identification by mass spectrometry. We also present an
      adaptation of the SPA system for the efficient purification and identification of
      protein complexes in E. coli and, potentially, other bacteria.

PMID- 15253428
TI  - Evaluation of the acid-cleavable isotope-coded affinity tag reagents: application
      to camptothecin-treated cortical neurons.
AB  - The new generation of isotope-coded affinity tag (ICAT) reagents have been
      evaluated by labeling an equimolar amount of bovine serum albumin (BSA) with ICAT
      12C9 and ICAT-13C9, combining the mixtures, digesting them with trypsin and
      analyzing the digestate both by muRPLC-tandem MS and by matrix-assisted laser
      desorption ionization (MALDI) TOF/TOF MS. The use of 13C in place of 2H resulted
      in both of the labeled peptides having identical elution characteristics in a
      reversed-phase separation. This similarity in elution allows ICAT-labeled
      peptides to be effectively analyzed using a muRPLC-MALDI-MS strategy as well. All
      of the cysteinyl-containing tryptic peptides from BSA were identified with only a
      10% variation in the relative abundance measurements between the light and heavy
      versions of each peptide. A facile method for the removal of contaminants that
      arise from the cleaved biotin moiety that otherwise interfere with downstream
      separations and MS analysis has also been developed. The new ICAT reagents were
      then applied to the analysis of a cortical neuron proteome sample to identify
      proteins regulated by the antitumor drug, camptothecin.

PMID- 15253429
TI  - The mighty arginine, the stable quaternary amines, the powerful aromatics, and
      the aggressive phosphate: their role in the noncovalent minuet.
AB  - In the age of proteomics, the role of certain amino acid residues and some post
      translational modifications in noncovalent complex formation are gaining in
      importance, as the understanding of interactions between biological molecules, is
      at the heart of the structure function relationship puzzle. In this work, mass
      spectrometry is used to highlight ammonium- or guanidinium-aromatic interactions
      through Cation-pi bonds and ammonium- or guanidinium-phosphate interactions
      through salt bridge formation. Such interactions are crucial factors in certain
      ligand-receptor interactions and receptor-receptor interactions. In addition, the
      ability of phosphorylated residues and phosphorylated lipids to form noncovalent
      complexes with guanidinium and quaternary ammonium (mostly through Coulombic
      interactions) is demonstrated, and could explain the stability of certain
      membrane embedded protein, or a possible role for phosphorylation in protein
      protein interactions. Dougherty's work demonstrates cation-pi interactions in
      intra-protein interactions and folding, the present work explores inter-peptide
      interactions, i.e., the formation of noncovalent complexes between peptides'
      epitopes containing adjacent aromatic residues and ones containing adjacent Arg
      as a model to better understand the role of cation-pi complexes in protein
      protein interaction. Complexes of peptides containing aromatic residues with
      quaternary amines as well as the interaction of aromatic compounds, with the
      guanidinium group of Arg are also investigated. Considering that an inordinate
      number of therapeutic compounds contain aromatic rings and quaternary amines, the
      above-described interactions could possibly be of great importance in better
      understanding their mechanism of action.

PMID- 15253430
TI  - Use of the phase diagram method to analyze the protein unfolding-refolding
      reactions: fishing out the "invisible" intermediates.
AB  - Partially folded conformations are important players in protein self
      organization, function, and misfolding, thus attracting the intensive and
      constant attention of researchers. Different conformational states of proteins
      can be easily discriminated from one another using the multiparametric approach,
      which usually involves the application of several physicochemical methods
      sensitive to the various structural levels of a protein molecule. This approach
      gives the most complete information about the structural changes in protein
      during its de- and renaturation. However, in many cases researches are interested
      in a brief and simple test for the appearance of an intermediate state. The
      binding of the hydrophobic fluorescent probe ANS represents one of the well
      established techniques, allowing the retrieval of such information. We are
      introducing another approach, based on the analysis of the spectroscopic data in
      a form of spectral diagrams. The essence of this method is to build the Ilambda1,
      versus Ilambda2 dependence, where Ilambda1 and Ilambda2 are the spectral
      intensity values (e.g., fluorescence, CD, FTIR, absorbance, etc.) measured on
      wavelengths lambda1 and lambda2. We are showing that this approach gives the
      detailed description of the protein unfolding pathway, detects the numerous
      partially folded species, and even fishes out the hidden intermediates. An
      application of this method for the analysis of the equilibrium and kinetic
      unfolding/refolding of several proteins under the variety of conditions is
      described. Advantages and disadvantages of the technique suggested are also
      discussed.

PMID- 15253431
TI  - Expanded coverage of the human heart mitochondrial proteome using
      multidimensional liquid chromatography coupled with tandem mass spectrometry.
AB  - Recent evidence suggests that mitochondria are closely linked with the aging
      process and degenerative disorders such as Alzheimer's disease and Parkinson's
      disease. Thus, there has been increasing interest in cataloging mitochondrial
      proteomes to identify potential diagnostic and therapeutic targets. We have
      previously reported results of a one-dimensional electrophoresis/liquid
      chromatography MS/MS study to characterize the proteome of normal human heart
      mitochondria (Taylor et al. Nat. Biotechnol. 2003, 21, 281-286). We now report
      two subsequent studies where multidimensional liquid chromatography MS/MS was
      investigated as an alternative means for characterizing the same sample.

PMID- 15253432
TI  - Association of rasGAPSH3 binding protein 1, G3BP1, and rasGap120 with integrin
      containing complexes induced by an adhesion blocking antibody.
AB  - The adhesion blocking antibody 3S3 was used to probe the regulation of
      alpha5beta1 integrin mediated adhesion in K562 cells. This antibody prevented
      cellular adherence but it did not interfere with ligand binding by cells or
      purified integrin. Interaction with 3S3 induced change in the cytoskeletal
      organization resulting in extensive filopodia formation. The antibody also
      prevented ligand and anti-integrin antibody induced phosphorylation of FAK in a
      trans acting fashion. MS based analysis of 3S3 induced integrin containing
      complexes identified rasGAP SH3 binding protein 1, G3BP1, as a component of these
      structures. The G3BP1 binding molecule, rasGap120, was also identified in the
      complexes. Microscopic examination confirmed the recruitment of a component of
      cellular G3BP1 and rasGap120 pools to sites of integrin cross-linking. G3BP1 was
      also observed in the 3S3 induced filopodia. In untreated cells, G3BP1 was shown
      to associate with submembranous regions involved in cellular polarization.
      Collectively, these results suggest that G3BP1 and rasGap120 can be recruited to
      sites of integrin ligation where they may play a role in cytoskeletal
      reorganization. Such changes may result in reduced adhesive potential and account
      for the 3S3 effects on cellular adhesion. It should be emphasized that these
      results do not necessarily indicate a direct interaction of integrin with G3BP1
      and rasGap120.

PMID- 15253433
TI  - Proteomic analysis of Trypanosoma cruzi developmental stages using isotope-coded
      affinity tag reagents.
AB  - Comparative proteome analysis of developmental stages of the human pathogen
      Trypanosoma cruzi was carried out by isotope-coded affinity tag technology (ICAT)
      associated with liquid cromatography-mass spectrometry peptide sequencing (LC
      MS/MS). Protein extracts of the protozoan trypomastigote and amastigote stages
      were labeled with heavy (D8) and light (D0) ICAT reagents and subjected to cation
      exchange and avidin affinity chromatographies followed by LC-MS/MS analysis. High
      confidence sequence information and expression levels for 41 T. cruzi
      polypeptides, including metabolic enzymes, paraflagellar rod components,
      tubulins, and heat-shock proteins were reported. Twenty-nine proteins displayed
      similar levels of expression in both forms of the parasite, nine proteins
      presented higher levels in trypomastigotes, whereas three were more expressed in
      amastigotes.

PMID- 15253434
TI  - Proteome annotations and identifications of the human pulmonary fibroblast.
AB  - We hereby report on a three year project initiative undertaken by our research
      team encompassing large-scale protein expression profiling and annotations of
      human primary lung fibroblast cells. An overview is given of proteomic studies of
      the fibroblast target cell involved in several diseases such as asthma, idiopatic
      pulmonary disease, and COPD. It has been the objective within our research team
      to map and identify the protein expressions occurring in both activated-, as well
      as resting cell states. The JGGL database www.2DDB.org has been built around
      these data, allowing advanced hypothesis building using the interactive query
      bioinformatic tools developed. Gene ontology has been applied to these
      annotations, classifying and correlating protein expressions to function. The
      localization as well as the biological processes involved for the annotations are
      being presented including an annotation-, and sequence-identification strategy,
      resulting in close to 2000 protein identities. Both gel based, high resolution 2D
      gels, and liquid-phase separation (three-dimensional HPLC), as well as the
      combination of gel- and LC-based approaches (1D-gels and nano-capillary LC,
      reversed-phase) were utilized. Protein sequencing and structure identities were
      acquired by a combination of MALDI-, and electrospray-mass spectrometry
      techniques. Phenotypical and morphological characterizations were also made for
      this human disease target cell in both stimulated- and resting-cell states. The
      use of functional assays that demonstrate the key regulating role of growth
      factors and cytokine stimuli such as PDGF, TGF-beta, and EGF and the effect of
      ECM molecules such as Biglycan, are also presented and discussed.

PMID- 15253435
TI  - Shotgun proteomics of Methanococcus jannaschii and insights into methanogenesis.
AB  - Methanococcus jannaschii is an autotrophic hyperthermophilic archaeon isolated
      from an oceanic hydrothermal vent. Its primary pathway for energy production is
      methanogenesis from H2 and CO2. High-throughput Multidimensional Protein
      Identification Technology based on microcapillary LC/LC/ MS/MS was used to
      investigate the proteome of M. jannaschii and the methanogenesis pathway in cells
      grown in complex medium with high H2 supply. A total of 963 proteins have been
      unambiguously identified. The identified proteins represent approximately 54% of
      the whole genome of M. jannaschii. About 44% of the identified proteins are
      either conserved hypothetical or hypothetical proteins. We identified 83-95% of
      the proteins predicted to be involved in amino acid biosynthesis, cellular
      processes, central intermediary metabolism, energy metabolism, protein synthesis,
      transcription, and purine, pyridine, nucleoside, and nucleotide synthesis. Over
      40% of these proteins have better than 50% sequence coverage. Approximately 90%
      of the predicted methanogenesis proteins were detected. In contrast, only 27-37%
      of predicted hypothetical proteins, proteins involved in transport and binding,
      and proteins with regulatory functions were identified. High peptide number,
      spectrum count, and sequence coverage have been used as indicators of high
      expression levels and are in good agreement with codon bias analysis. Predicted
      intein peptides were detected in MJ1043 (DNA-directed RNA polymerase, subunit
      A"), MJ0542 (phosphoenolpyruvate synthase), MJ0782 (transcription initiation
      factor IIB), and MJ1422 (putative replication factor C subunit). New peptides
      created by protein splicing were detected in MJ0885 (DNA dependent DNA
      polymerase), MJ0542, and MJ0782. The methanogenesis pathway and the enzymes
      involved are also discussed.

PMID- 15253436
TI  - Proteomic analysis of SARS associated coronavirus using two-dimensional liquid
      chromatography mass spectrometry and one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis followed by mass spectroemtric analysis.
AB  - The proteomes of the severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) and its infected Vero E6 cells were detected in the present study. The
      cytosol and nucleus fractions of virus-infected cells as well as the crude
      virions were analyzed either by one-dimensional electrophoresis followed by ESI
      MS/MS identification or by shotgun strategy with two-dimensional liquid
      chromatography-ESI-MS/MS. For the first time, all of the four predicted
      structural proteins of SARS-CoV were identified, including S (Spike), M
      (Membrane), N (Nucleocapsid), and E (Envolope) proteins. In addition, a novel
      phosphorylated site of M protein was observed. The combination of these gel-base
      and non-gel methods provides fast and complimentary approaches to SARS-CoV
      proteome and can be widely used in the analysis of other viruses.

PMID- 15253437
TI  - A new strategy for identification of N-glycosylated proteins and unambiguous
      assignment of their glycosylation sites using HILIC enrichment and partial
      deglycosylation.
AB  - Characterization of glycoproteins using mass spectrometry ranges from
      determination of carbohydrate-protein linkages to the full characterization of
      all glycan structures attached to each glycosylation site. In a novel approach to
      identify N-glycosylation sites in complex biological samples, we performed an
      enrichment of glycosylated peptides through hydrophilic interaction liquid
      chromatography (HILIC) followed by partial deglycosylation using a combination of
      endo-beta-N-acetylglucosaminidases (EC 3.2.1.96). After hydrolysis with these
      enzymes, a single N-acetylglucosamine (GlcNAc) residue remains linked to the
      asparagine residue. The removal of the major part of the glycan simplifies the
      MS/MS fragment ion spectra of glycopeptides, while the remaining GlcNAc residue
      enables unambiguous assignment of the glycosylation site together with the amino
      acid sequence. We first tested our approach on a mixture of known glycoproteins,
      and subsequently the method was applied to samples of human plasma obtained by
      lectin chromatography followed by 1D gel-electrophoresis for determination of 62
      glycosylation sites in 37 glycoproteins.

PMID- 15253438
TI  - Capillary isoelectric focusing with laser-induced fluorescence whole column
      imaging detection as a tool to monitor reactions of proteins.
AB  - Capillary isoelectric focusing (CIEF) with laser-induced fluorescence (LIF) whole
      column imaging detection (WCID) has the characteristics of high resolution, high
      speed and high sensitivity for separation of amphoteric biomolecules. These
      features enable a CIEF-LIF-WCID system to monitor the dynamic process of a
      protein reaction. The reaction can be a physical change or a chemical reaction,
      provided that the kinetics of the reaction is slower than the focusing speed or
      that the intermediates involved have long enough life-span compared to the
      analysis time. The processes of denaturation (a physical reaction), reduction and
      carbamylation (both chemical reactions) were dynamically monitored. The CIEF
      profiles at successive reaction times clearly displayed the formation of
      different products at different stages. At incomplete denaturation, intermediates
      with higher apparent pI values relative to the products at complete denaturation
      were detected. Carbamylation products of a protein were detected when the protein
      reacted with a urea solution that had prepared three months earlier, exhibiting
      gradually decreased pI values. Mechanisms involved in these reactions were
      rationalized. A combined mechanism of denaturation and reduction was suggested to
      explain the denaturing process under high concentrations of urea. Potential
      applications and critical factors to manipulate these reactions were also
      discussed.

PMID- 15253439
TI  - Molecular analysis of homocysteic acid-induced neuronal stress.
AB  - Hyperhomocysteinemia is a risk factor for vascular and neuronal lesions often
      observed with concomitant high levels of homocysteic acid. In contrast to
      homocysteine, homocysteic acid induces calcium influx into neurons, with
      characteristics of an excitotoxic glutamatergic agonist at elevated
      concentrations. On the molecular level this is correlated to fast modifications
      of proteins (phosphorylation and proteolysis). Within the homocysteic acid
      induced molecular signature we focused in more detail on phosphorylation of two
      proteins implicated as risk factors in schizophrenia and neurodegeneration:
      Dihydropyrimidinase related protein and 14-3-3 protein isoforms. Among the
      identified proteins there are known chaperones and oxidative metabolism enzymes,
      but a few are new in context of neuronal stress: Lasp-1, a vitamin D associated
      factor and an expressed sequence with features of a Rho GDP dissociation
      inhibitor. Moreover, we detect a specific proteolytic processing of heat shock
      protein 70 and proteindisulfide isomerase, which is abolished by vitamins (folic
      acid, vitamin B12, and vitamin B6), which also decrease elevated intracellular
      calcium levels induced by homocysteic acid.

PMID- 15253440
TI  - High-throughput cloning of Campylobacter jejuni ORfs by in vivo recombination in
      Escherichia coli.
AB  - A rate-limiting and costly step in many proteomics analyses is the cloning of all
      of the ORFs for an organism into technique-specific vectors. Here, we describe
      the generation of a Campylobacter jejuni expression clone set using a high
      throughput cloning approach based on recombination in E. coli. The approach uses
      native E. coli recombination functions and requires no in vitro enzymatic steps
      or special strains. Our results indicate that this approach is an efficient and
      economical alternative for high-throughput cloning.

PMID- 15253441
TI  - Quantitative analysis of tryptic protein mixtures using electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry.
AB  - For the first time, quantitative analysis of tryptic protein mixtures, labeled
      with Quantification-Using-Enhanced-Signal-Tags (QUEST)-markers, were performed
      with electrospray ionization and a 9.4 T Fourier Transform Ion Cyclotron
      Resonance (FTICR) mass spectrometer. Coupling a High-Pressure Liquid
      Chromatography (HPLC) separation step prior to mass analysis resulted in an
      increased amount of identified labeled tryptic peptides. The range for the
      determined intensity ratios of two peptides in a labeled pair was large, but the
      obtained median intensity ratio correlated very well with the corresponding
      concentration ratio. This method can be used for observing protein dynamics in a
      specific cell type, tissue, or in body fluids.

PMID- 15253442
TI  - Characterization of the Salmonella typhimurium proteome by semi-automated two
      dimensional HPLC-mass spectrometry: detection of proteins implicated in multiple
      antibiotic resistance.
AB  - The proteome of Salmonella enterica serovar Typhimurium was characterized by 2
      dimensional HPLC mass spectrometry to provide a platform for subsequent proteomic
      investigations of low level multiple antibiotic resistance (MAR). Bacteria (2.15
      +/- 0.23 x 10(10) cfu; mean +/- s.d.) were harvested from liquid culture and
      proteins differentially fractionated, on the basis of solubility, into
      preparations representative of the cytosol, cell envelope and outer membrane
      proteins (OMPs). These preparations were digested by treatment with trypsin and
      peptides separated into fractions (n = 20) by strong cation exchange
      chromatography (SCX). Tryptic peptides in each SCX fraction were further
      separated by reversed-phase chromatography and detected by mass spectrometry.
      Peptides were assigned to proteins and consensus rank listings compiled using
      SEQUEST. A total of 816 +/- 11 individual proteins were identified which included
      371 +/- 33, 565 +/- 15 and 262 +/- 5 from the cytosolic, cell envelope and OMP
      preparations, respectively. A significant correlation was observed (r2 = 0.62 +/-
      0.10; P < 0.0001) between consensus rank position for duplicate cell preparations
      and an average of 74 +/- 5% of proteins were common to both replicates. A total
      of 34 outer membrane proteins were detected, 20 of these from the OMP
      preparation. A range of proteins (n = 20) previously associated with the mar
      locus in E. coli were also found including the key MAR effectors AcrA, TolC and
      OmpF.

PMID- 15253443
TI  - Proteomic analysis of ductal carcinoma of the breast using laser capture
      microdissection, LC-MS, and 16O/18O isotopic labeling.
AB  - The goal of this study was the development of a method for quantitative
      expression proteomics on the limited sample amounts obtained through laser
      capture microdissection (LCM) of tissues, e.g., approximately 10 000 cells, which
      typically contain roughly 1-4 microg protein. The 16O/18O labeling method was
      selected as an approach to measure differential expression. A sample preparation
      protocol including lysis, digestion and 16O/18O labeling was first developed for
      LCM cell samples. The selected protocol was examined using two LCM caps of 10 000
      cells from invasive ductal carcinoma of the breast and shown to be repeatable. A
      further test of LC-IT-MS/MS in combination with the 16O/18O post-digestion
      labeling method for studying low level samples was conducted first on a single
      protein (BSA) and then on a 5-standard protein mixture digest of different
      protein amounts, each with a total content approximately 1 microg. Next, protein
      expression was compared between 10 000 cells, each of microdissected normal
      ductal epithelium and metastatic ductal carcinoma, using the developed method.
      The proteins from the microdissected cells were extracted, precipitated, digested
      with trypsin and then 16O/18O labeled. The normal and metastatic cell samples
      were analyzed using reversed phase LC-ESI-MS/MS on the ion trap mass
      spectrometer. A total of 76 proteins were identified. Some, such as mitochondrial
      isocitrate dehydrogenase, actin and 14-3-3 protein xi/delta were found to be
      significantly up-regulated in the breast tumor cells.

PMID- 15253444
TI  - Highly UV-absorbing complex in selenomethionine-substituted alcohol dehydrogenase
      from Sulfolobus solfataricus.
AB  - The aim of this work was to explain the previously discovered effect of
      significant decrease in intrinsic fluorescence intensity of SsADH caused by
      replacement of S atoms of methionine residues to Se (Giordano, A.; Raia, C. A. J.
      Fluorescence 2003, 13, 17-24) on the basis of the analysis of its 3D structure.
      It was found that all selenium atoms are located far from both Trp95 and Trp117
      and could not cause their fluorescence quenching. At the same time, it was
      determined that substitution of S by Se causes enhanced protein absorption in the
      UV-region. This effect was explained by the formation of Se complex with some
      groups of protein. It was revealed that this complex does not participate in
      fluorescence and does not transfer excitation energy to tryptophan or tyrosine
      residues.

PMID- 15253445
TI  - Novel linear quadrupole ion trap/FT mass spectrometer: performance
      characterization and use in the comparative analysis of histone H3 post
      translational modifications.
AB  - We describe the design and performance of a prototype high performance hybrid
      mass spectrometer. This instrument consists of a linear quadrupole ion trap (QLT)
      coupled to a Fourier transform ion cyclotron resonance mass analyzer (FTMS). This
      configuration provides rapid and automated MS and MS/MS analyses, similar to the
      "data dependent scanning" found on standard 3-D Paul traps, but with
      substantially improved internal scan dynamic range, mass measurement accuracy,
      mass resolution, and detection limits. Sequence analysis of peptides at the
      zeptomole level is described. The recently released, commercial version of this
      instrument operates in the LC/MS mode (1 s/scan) with a mass resolution of 100
      000 and is equipped with automatic gain control to provide mass measurement
      accuracy of 1-2 ppm without internal standard. Methodology is described that uses
      this instrument to compare the post-translational modifications present on
      histone H3 isolated from asynchronously growing cells and cells arrested in
      mitosis.

PMID- 15253446
TI  - Proteome and transcriptome analysis of retinoic acid-induced differentiation of
      human acute promyelocytic leukemia cells, NB4.
AB  - Acute promyelocytic leukemia (APL) is characterized by a translocation t(15:17)
      that fuses the retinoic acid receptor gene with the promyelocytic gene, which
      blocks differentiation to normal granulocytes. NB4 cells, derived from human
      acute promyelocytic leukemia, display this genotype and phenotype. All trans
      retinoic acid (ATRA) induces differentiation of NB4 cell cultures in vitro and
      APL in vivo, although resistance to differentiation therapy frequently develops.
      To identify genes involved in differentiation, we compared gene expression at the
      mRNA and protein levels using microarray analyses and two-dimensional (2D)
      difference gel electrophoresis (DIGE), plus MALDI-TOF-TOF mass spectrometry.
      Differentially expressed transcripts were identified using oligonucleotide-based
      microarrays with targets representing almost 14 000 genes. Real time PCR was
      performed on a subset of genes whose products were shown to be differentially
      expressed using proteomic and/or genomic approaches. Our analyses identified 46
      genes that were differentially expressed in NB4 +/- ATRA; 22 were identified
      using 2D-DIGE and 24 using microarray analysis. All but four of these genes were
      expressed at higher levels in differentiated cells, and several controlled cell
      structure (internal and cytoskelatal) or signal transduction. We observed that
      proteome analysis with DIGE and silver-stained 2D gel electrophoresis analyses
      revealed significant differences between the two measurement approaches.
      Furthermore, our data showed significant discordance between gene expression at
      the protein and transcript levels.

PMID- 15253447
TI  - Protein expression profiling of endometrial malignancies reveals a new tumor
      marker: chaperonin 10.
AB  - Endometrial carcinoma is a common malignancy in women, being exceeded in
      incidence only by that of breast, lung, and colorectal cancers. At present, no
      serum tumor markers are available for the monitoring of endometrial carcinoma
      patients, and patients with recurrent disease are detected only following the
      development of symptoms or abnormalities in imaging assessments. Similarly, no
      screening tools are available for endometrial carcinoma. Protein profiling by
      matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry
      (MALDI-TOF MS) has proven to be a sensitive and fast method of analysis for small
      proteins or peptides to yield specific biomarkers. In this study, a variety of
      normal and malignant endometrial tissue samples were fractionated and analyzed by
      SELDI-TOF MS (SELDI is a version of MALDI utilizing protein "chips"). A number of
      proteins displayed differential expression in malignant endometrial tissues. One
      of the prominent proteins fractionated by weak cation exchange chromatography and
      displaying enhanced expression in these malignant tissues was identified as
      chaperonin 10. The increased expression of chaperonin 10 in malignant endometrial
      tissues was further confirmed by parallel Western blot and immunohistochemistry
      analyses.

PMID- 15253448
TI  - Absolute quantification of the model biomarker prostate-specific antigen in serum
      by LC-Ms/MS using protein cleavage and isotope dilution mass spectrometry.
AB  - Protein cleavage-isotope dilution mass spectrometry (PC-IDMS) can be used to
      quantify proteins, with an isotope-labeled analogue of the peptide fragment used
      as an internal standard. Here, we investigate use of a standard LC-MS/MS platform
      for quantifying a model biomarker directly from serum by this technique. We
      synthesized a peptide (IVGGWECEK) identical to the N-terminal tryptic fragment of
      PSA but with each glycine containing two 13C atoms and one 15N atom. PSA-free
      human serum was denatured with urea followed by the introduction of PSA standard
      and the stable isotope labeled internal standard peptide. The sample was then
      proteolyzed with trypsin and subjected to quantification using LC-MS/ MS on a
      triple quadrupole mass spectrometer. A linear least squares calibration curve
      made from five different concentrations of PSA added to serum and digested (each
      made in triplicate and randomly injected three times) had a mean slope of 0.973
      (SE = 0.023), intercept of -0.003 (SE = 0.022), and R2 of 0.971. Recovery of
      calibrators ranged from 70 to 85% with a mean run-to-run CV of 13% and a mean
      within-run CV of 5.7%. PC-IDMS is a promising technique for quantifying proteins
      covering a broad range of applications from standardizing immunoassays to
      monitoring post-translational modifications to quantifying newly discovered
      biomarkers prior to the development and implementation of an immunoassay, just to
      name a few. Issues surrounding the application of PC-IDMS for the absolute
      quantification of proteins include selection of a proteolytic fragment for
      quantification that can be cleaved and isolated reproducibly over a broad dynamic
      range, stable isotope labeled synthetic peptide standards that give consistent
      results, and LC-MS/MS methods that provide adequate sensitivity and
      reproducibility without creating impractical analysis times. The results
      presented here show that absolute quantification can be performed on the model
      biomarker PSA introduced into denatured serum when analyzed by LC-MS/MS. However,
      concerns still exist regarding sensitivity compared to existing immunoassays as
      well as the reproducibility of PC-IDMS performed in different matrixes.

PMID- 15253449
TI  - Fast proteolytic digestion coupled with organelle enrichment for proteomic
      analysis of rat liver.
AB  - The use of an acid-labile surfactant as an alternative to urea denaturation
      allows for same-day proteolytic digestion and fast cleanup of cellular lysate
      samples. Homogenized rat liver tissue was separated into four fractions enriched
      in nuclei, mitochondria, microsomes (remaining organelles), and cytosol. Each
      subcellular fraction was then subjected to proteolytic digestion with trypsin for
      2 h after denaturing with an acid-labile surfactant (ALS), separated by nanoflow
      reversed phase HPLC, and mass analyzed by tandem mass spectrometry in a 3-D ion
      trap. The results obtained from ALS denaturation for both organelle enrichment
      and whole cell lysate samples were comparable to those obtained from aliquots of
      the same samples treated by reduction, alkylation, and urea denaturation. Each
      method resulted in a similar number of peptides (694 for urea, 674 for ALS) and
      proteins (225 for urea, 229 for ALS) identified, with generally the same proteins
      (47% overlap) identified. As expected, organelle enrichment enabled the
      identification of more proteins (66% more with urea, 60% more with ALS) compared
      to a whole cell lysate. With organelle enrichment, the number of proteins with
      equal or increased sequence coverage went up by 73% with urea and 67% with ALS
      compared to the whole cell lysate. Additional information regarding the
      subcellular location of many proteins is obtained by organelle enrichment. While
      organelle enrichment is demonstrated with a bottom-up proteomics approach, it
      should be easily amenable to top-down proteomics approaches.

PMID- 15253450
TI  - Evaluation of a cleavable stable isotope labeled synthetic peptide for absolute
      protein quantification using LC-MS/MS.
AB  - Protein cleavage coupled with isotope dilution mass spectrometry (PC-IDMS) has
      the potential to provide the absolute concentration of a specific protein, or
      multiple proteins, in complex mixtures. However, PC-IDMS differs from standard
      IDMS since the internal standard is a different molecule than the analyte at the
      start of the experiment, more specifically, the internal standard is a peptide
      and the analyte is a protein prior to cleavage. It is not until after the
      cleavage process that the stable isotope labeled synthetic peptide has the same
      physicochemical behavior as the peptide cleaved from the protein. The work
      presented here evaluates the use of tryptic cleavage sites incorporated into the
      internal standard synthetic peptide in an attempt to create an internal standard
      that has cleavage characteristics more similar to the protein being quantified.
      Results presented here suggest that an internal standard synthetic peptide
      incorporating internal cleavage sites does not improve the accuracy and precision
      of the values obtained when performing PC-IDMS.

PMID- 15253451
TI  - Mass spectrometric identification of RNA binding proteins from dried EMSA gels.
AB  - Electrophoretic mobility shift assays (EMSA) are commonly employed for the
      analysis of nucleic acid/ protein interactions with a native gel system. Here, we
      report a method to identify RNA binding proteins from a dried EMSA gel by mass
      spectrometry following autoradiography. Compared to wet gel exposure, our
      approach resulted in an improved protein identification sensitivity and
      RNA/protein complex isolation accuracy. The method described here is useful for
      the large scale characterization of RNA- or DNA-protein complexes.

PMID- 15253452
TI  - Simple method for three-dimensional representation of 2-DE spots using a
      spreadsheet program.
AB  - Quantitative protein expression analysis based on two-dimensional gel
      electrophoresis requires comparison of spot volumes. We describe an algorithm to
      visualize two-dimensional spot patterns in three dimensions using a spreadsheet
      program for surface plotting.

PMID- 15253453
TI  - Suffocation of nerve fibers by living nanovesicles: a model simulation.
AB  - A model using nanospheres to allow the simulation of the nonspecific interaction
      of nanobacteria (NB), one with another or with body tissues, is established.
      Depending primarily on their concentrations and stress levels, these apatite
      nanovesicles may nucleate thrombogenic conglomerates in blood, or self-assemble
      to dense nanoclay layers on surfaces in the body. Partial or total encapsulation
      of nerve fiber bundles by such mineral layers may interrupt the metabolic
      exchanges between the surrounded tissue and its immediate environment and may
      restrict signaling processes. The presented model could provide detailed insight
      into plaque formation triggered by NB, and the parameters encouraging it.

PMID- 15253454
TI  - Could reduced bone mineral densities in HIV be caused by nanobacteria?
AB  - From the observations of different research groups reporting on reduced bone
      mineral density (BMD) and on a pronounced tendency for kidney stone formation,
      both in HIV-infected patients, and from results achieved in the treatment of
      severest peripheral neuropathy with lasers, it is concluded that nanobacteria
      (NB) could actively contribute to the reduction of BMD. A reduced BMD could
      primarily stem from NB, extracting calcium and phosphate from blood, affecting
      the calcium and phosphate homeostasis in humans.

PMID- 15253455
TI  - Fresh concepts in dental design.

PMID- 15253456
TI  - The new reality.

PMID- 15253457
TI  - Managing the amelogenesis imperfecta patient.

PMID- 15253458
TI  - Making a difference.

PMID- 15253459
TI  - The extraordinary vulnerability of people with disabilities: guidelines for oral
      health professionals.
AB  - In the last 40 years, there has been a dramatic shift in living arrangements for
      people with disabilities from large state institutions to community-based care.
      This shift has required communities to increase their clinical capacity including
      oral health care systems. Oral health professionals must be cognizant that the
      rate of abuse and neglect experienced by people with developmental disabilities
      and other special needs is at least four times the rate experienced by the
      general population. These trends have resulted in additional responsibility on
      community oral health professionals to provide oral health services for many
      people who formerly lived in state institutions including recognizing and
      reporting suspected abuse and neglect. Oral health professionals must prepare
      themselves to successfully carry out these professional responsibilities.

PMID- 15253460
TI  - Culturally competent responses for identifying and responding to domestic
      violence in dental care settings.
AB  - Dental care providers can play an important role in identifying and preventing
      intimate partner violence. Many victims of domestic violence interact with dental
      care providers, including dentists, dental hygienists, and dental assistants,
      thus placing dental professionals in a unique position to screen for early
      identification and even primary prevention of abuse. An effective and successful
      response to intimate partner violence in a dental care setting involves creating
      a safe and culturally competent environment for screening and disclosure, giving
      supportive messages to victims, educating patients about abuse and connection to
      health, offering strategies to promote safety, and informing clients about
      relevant community resources.

PMID- 15253461
TI  - The health impact of intimate partner violence.
AB  - Research suggests that between 960,000 to 4 million individuals are victims of
      intimate partner violence (IPV) each year and of these about 85 percent are
      women. In a recent survey conducted by the Commonwealth Fund, it was estimated
      that approximately one-third of American women will become a victim of IPV at
      some point in their life. The literature reports 36 percent to 95 percent of
      battered women suffer injuries to the face, neck or head. Women who have been
      abused by a partner report significantly lower self assessments of health,
      increased disabilities and increased chronic health conditions than non-abused
      women. When direct costs to the health care system are combined with indirect
      costs to society, total health care costs of IPV can escalate into the billions.
      Intimate partner violence erodes the health of patients, consumes healthcare
      dollars, compromises the health and safety of children and communities, and
      represents a liability exposure for the healthcare clinician who turns their
      head. Healthcare providers, especially dental professionals, must gain experience
      in the diagnosis and management of IPV so that identification occurs earlier and
      intervention follows established protocols.

PMID- 15253462
TI  - Domestic violence: no place for a smile.
AB  - Because dentists routinely assess a patient's head, neck and mouth, they have a
      unique and excellent opportunity to recognize whether or not a patient is being
      abused. This article seeks to enlist the collaboration of the dental community in
      the effort to prevent domestic/intimate partner violence and provide more
      information about the signs and symptoms of domestic violence injuries, including
      strangulation, which is often overlooked by medical and dental professionals.
      Strangulation has only been identified in recent years as one of the most lethal
      forms of domestic violence. Unconsciousness may occur within seconds and death
      within minutes. It is known that victims may have no visible injuries whatsoever
      yet because of underlying brain damage by a lack of oxygen from being strangled,
      victims may have many serious internal injuries or die days or several weeks
      later. Strangulation is often indicative of a high level of domestic violence in
      a relationship. Attempted strangulation may cause physiological changes evident
      in the course of a dental examination. For these reasons, dentists should be
      vigilant in looking for its symptoms.

PMID- 15253463
TI  - Forensic odontology: a global activity.
AB  - Forensic odontology is an important and expanding field of dentistry. The
      application of these forensic techniques in identification, criminal justice and
      dental liability are being practiced worldwide. In some mass disaster events,
      notably large commercial aircraft crashes, the traumatic forces are such that
      fragmentation and conflagration result in only the most durable of human tissues
      dentition survive and become a potential source of identification.

PMID- 15253464
TI  - Dental reimbursement: helping victims smile again.
AB  - By educating themselves and their staff members about services for crime victims,
      dentists play a crucial role in helping crime victims receive the care they need.
      When a crime victim needs dental work, they may be unaware of the other
      assistance available through the Victims Compensation Program. Dental care made
      possible through compensation helps victims begin to heal.

PMID- 15253465
TI  - Frill-free dentistry...And don't forget your own bur.

PMID- 15253467
TI  - Ankle-brachial pressure index measured using an automated oscillometric method as
      a predictor of the severity of coronary atherosclerosis in patients with coronary
      artery disease.
AB  - Ankle-brachial pressure index (ABI) measured using a conventional Doppler method
      is an independent predictor of the number of coronary vessels affected in
      coronary artery disease (CAD). Recently, a new clinical device has been developed
      to measure ABI using an oscillometric method. It is unclear whether ABI measured
      using this device is a significant predictor of the severity of coronary
      atherosclerosis. We retrospectively included 87 patients from our outpatient
      clinic who had ever undergone coronary angiography. ABI was determined in all
      subjects using the new ABI-form device. The lower value of ABI in either limb was
      used for analysis. We divided our subjects into two groups, with either ABI less
      than 0.9 or at least 0.9, and compared basal characteristics between groups. We
      analyzed the relationship between ABI and the severity of CAD. In addition, we
      calculated the sensitivity, specificity, and positive and negative predictive
      values of ABI less than 0.9 in predicting multivessel (two-vessel + three-vessel)
      involvement in our patients. There were 15 patients with ABI less than 0.9 and 72
      with ABI at least 0.9. Patients with ABI less than 0.9 were older and had higher
      plasma levels of uric acid. The prevalence of diabetes mellitus, hypertension,
      smoking, and diuretic use was significantly higher in patients with ABI less than
      0.9. In addition, the group with ABI less than 0.9 had a lower prevalence of one
      vessel CAD and higher prevalence of three-vessel or multivessel CAD. The
      sensitivity, specificity, and positive and negative predictive values of ABI less
      than 0.9 in predicting multivessel CAD were 22%, 96%, 93%, and 34%, respectively.
      In conclusion, ABI measured using the automated oscillometric method can be used
      to predict the severity of coronary atherosclerosis in patients with CAD.

PMID- 15253466
TI  - In vitro activities of antibiotic combinations against clincal isolates of
      Pseudomonas aeruginosa.
AB  - Combination therapy has been recommended to treat Pseudomonas aeruginosa
      infections worldwide. The purpose of the present study was to determine the in
      vitro activities of piperacillin, cefepime, aztreonam, amikacin, and
      ciprofloxacin alone and in combination against 100 clinical isolates of P.
      aeruginosa from one medical center in southern Taiwan. The combination
      susceptibility assay was performed using the checkerboard technique. The
      percentage of resistance of P. aeruginosa to single agents in our study was
      relatively high for the Asia-Pacific area, except to aztreonam. Piperacillin plus
      amikacin exhibited the highest potential for synergy (59/100) in this study.
      Moreover, a high percentage of synergism was also noted with amikacin combined
      with cefepime (7/100) or aztreonam (16/100). The combination of two beta-lactams,
      such as cefepime with piperacillin, and aztreonam with cefepime or piperacillin,
      showed synergistic effects against some P. aeruginosa isolates. Although
      ciprofloxacin is a good anti-pseudomonal agent, a very low potential for synergy
      with other antibiotics was demonstrated in this study. No antagonism was
      exhibited by any combination in our study. Among piperacillin-resistant strains,
      there was synergy with a beta-lactam plus amikacin, including the combination of
      piperacillin and amikacin. However, the combination of two beta-lactams, such as
      piperacillin and cefepime or aztreonam, did not have any synergistic activity
      against these strains. In summary, the combinations of amikacin with the tested
      beta-lactams (piperacillin, aztreonam, cefepime) had a greater synergistic effect
      against P. aeruginosa, even piperacillin-resistant strains, than other
      combinations. Understanding the synergistic effect on clinical strains may help
      clinicians choose better empirical therapy in an area with high prevalence of
      multidrug-resistant P. aeruginosa.

PMID- 15253468
TI  - Relationships between American Urological Association symptom index, prostate
      volume, and disease-specific quality of life question in patients with benign
      prostatic hyperplasia.
AB  - The American Urological Association (AUA) symptom index is both valid and
      reliable in identifying the need to treat patients with benign prostatic
      hyperplasia (BPH) and in monitoring their response to therapy. We evaluated the
      relationships between AUA symptom index, disease-specific quality of life
      question, and prostate volume in patients with BPH. A total of 100 patients who
      came to Kaohsiung Medical University Hospital, Taiwan, for help due to lower
      urinary tract symptoms (LUTS) and who were diagnosed with BPH between October
      2002 and June 2003 were included in the study. All patients were evaluated using
      transrectal ultrasonography, AUA symptom index, and disease-specific quality of
      life question. The disease-specific quality of life question showed good
      correlation with AUA symptom score (r = 0.815, p < 0.01), but weak correlation
      with prostate volume (r = 0.225, p < 0.05) and age (r = 0.274, p < 0.05).
      Prostate volume had weak correlation with AUA symptom score (r = 0.251, p < 0.05)
      and age (r = 0.472, p < 0.01), but good correlation with prostate specific
      antigen (r = 0.638, p < 0.01). In addition to AUA symptom index, we suggest using
      the disease-specific quality of life question to evaluate the influence on
      quality of life and response to treatment in clinical practice. Moreover, we
      should assess the impact of BPH symptoms rather than the increase in prostate
      volume during the management of BPH.

PMID- 15253469
TI  - Risk factors for cardiovascular disease in the elderly in Taiwan.
AB  - The major objective of the present study was to identify biologic and behavioral
      risk factors of cardiovascular disease (CVD) in the elderly population in Taiwan.
      It is hypothesized that the selected risk factors are significantly associated
      with the prevalence of CVD. Data came from a nationwide geriatric survey in 1991.
      Stratified proportional sampling was used to recruit 2,600 subjects. These were
      evaluated by family physicians working for the Departments of Family Medicine at
      four medical centers in four major cities in Taiwan. Univariate and multivariate
      logistic regression analyses were used to examine the associations between risk
      factors and the prevalence of CVD. The prevalence of CVD was 38.31%. Patients
      with CVD consistently had higher values for each selected risk factor except high
      density lipoprotein-cholesterol (HDL-C) and glucose concentrations. The findings
      also indicated that hypertension, hypertriglyceridemia, low HDL-C concentration,
      ex-drinking status, and overweight were significantly associated with the
      prevalence of CVD among the elderly in Taiwan. The findings not only confirm the
      risk factors for CVD, but also invite more attention to be given to the
      importance of biologic and behavioral risk factors in CVD.

PMID- 15253470
TI  - Validation of comprehensive assessment of activities of daily living in stroke
      survivors.
AB  - This study determined whether the Functional Independence Measure (FIM) and the
      Frenchay Activities Index (FAI) could be used together as a more comprehensive
      score to assess the activities of daily living (ADL) in stroke survivors.
      Subjects were recruited from stroke patients consecutively admitted to the
      inpatient neurology or rehabilitation department at a university hospital in
      southern Taiwan. We interviewed 209 first stroke survivors at least 1 year after
      stroke onset during their clinical visits, at home, or in long-term care
      institutions. Combinations of FIM and FAI as a comprehensive assessment of ADL
      were measured. All items of the FIM and the FAI were included in a non-parametric
      factor analysis to determine their underlying constructs. Two comprehensive
      functional independence scores were then computed as functions of the FIM and FAI
      scores. The distributional characteristics of the comprehensive scores were
      examined. Approximately 90% of the total variation was explained by three
      factors. One single factor comprised all the items from FIM, while the FAI items
      loaded on two other factors, suggesting that FIM supplements FAI without overlap
      in content. We further demonstrated that the presence of ceiling or floor effects
      when either the FIM or the FAI was used could be removed using combined scores of
      the two instruments. The FIM and the FAI assessed different domains with good
      construct validity. A comprehensive assessment of functional independence
      obtained by combining the FIM and the FAI scores is potentially more appropriate
      and useful for clinical and research applications in stroke patients.

PMID- 15253471
TI  - Obsessive-compulsive symptoms associated with clozapine and risperidone
      treatment: three case reports and review of the literature.
AB  - Treatment-emergent obsessive-compulsive symptoms (OCSs) have raised concern since
      the widespread introduction of serotonin-dopamine antagonists (SDAs) for the
      treatment of schizophrenia. Further investigations of SDA-emergent OCSs and their
      response to anti-obsessional agents will be beneficial for clinicians in helping
      patients who suffer from this problem. We present three cases of schizophrenia in
      which distressing OCSs occurred during clozapine or risperidone treatment. OCSs
      were assessed consecutively using the Yale-Brown Obsessive-Compulsive Scale. The
      OCSs of these three patients were responsive to anti-obsessional agents,
      including fluvoxamine, clomipramine, and paroxetine. We also review the current
      literature and discuss the possible pathophysiology and psychopathology of SDA
      emergent OCSs.

PMID- 15253472
TI  - Molecular and histopathologic evidence for systemic infection by Mycobacterium
      bovis in a patient with tuberculous enteritis, peritonitis, and meningitis: a
      case report.
AB  - Mycobacterium bovis infection has been reported in several patients with AIDS in
      other countries. The prevalence of tuberculosis in Taiwan is higher than the
      World Health Organization standard. However, reports of M. bovis infection are
      rare. A 47-year-old male had the habit of drinking uncooked fresh deer's blood
      and unpasteurized deer's milk. He suffered from acute abdominal pain and
      underwent emergency laparotomy. Pathology demonstrated tuberculosis enteritis
      with colon perforation. The molecular diagnosis by nested polymerase chain
      reaction assay and single-strand conformation polymorphism assay showed M. bovis
      infection in the small intestine, mesenteric lymph nodes, and cerebrospinal fluid
      (CSF). Our results suggest that the most likely portal of entry of M. bovis is
      the gastrointestinal rather than the respiratory tract. Ingested M. bovis from
      unpasteurized deer's milk probably entered the mucosal macrophages of the
      intestine and then the draining mesenteric lymph nodes. As immunity declined,
      bacilli from the mesenteric lymph nodes disseminated to other organs and into the
      CSF.

PMID- 15253473
TI  - Cerebral radionecrosis with cystic degeneration following radiotherapy for nasal
      cavity squamous cell carcinoma: a case report.
AB  - A 31-year-old man with nasal cavity squamous cell carcinoma was treated in our
      hospital with two courses of radiotherapy (120 Gy total dose) followed by
      surgical tumor resection. Three years after the last irradiation, he developed
      seizures as well as changes in behavior and consciousness. Medical therapy with
      diphenylhydantoin (Dilantin) terminated the seizures. Dysphagia, unsteady gait,
      and right-side limb weakness developed 37 months after the onset of seizures.
      Magnetic resonance imaging showed a large, cystic mass in the left temporal lobe
      with left to right midline shift. Following craniotomy with decompression of the
      cystic mass, the patient improved clinically. No malignant cells were found in
      the specimen. No further progression of neurologic symptoms was noted after a 1
      year follow-up. Cerebral radionecrosis is an uncommon late complication of
      radiotherapy and needs to be differentiated from tumor recurrence or metastasis
      if the irradiation field covers the cerebral region in patients with head and
      neck malignancies.

PMID- 15253474
TI  - In another time.

PMID- 15253475
TI  - Performance enhancement drugs: safe and effective?

PMID- 15253476
TI  - West Nile virus infection in western South Dakota: clinical findings and future
      diagnostic considerations for cost savings.

PMID- 15253477
TI  - Incidence of hyperkalemia in high risk patients during treatment with an
      angiotensin converting enzyme inhibitor (Lisinopril) versus an angiotensin II
      receptor blocker (Losartan).
AB  - Hyperkalemia is a known side effect during treatment with Angiotensin Converting
      Enzyme Inhibitors (ACEIs). The purpose of this study was to compare the effect of
      an ACEI (Lisinopril) to an Angiotensin II Receptor Blocker (Losartan) on serum
      potassium (K) level in patients with known history of high normal serum K (mean =
      4.8) while on treatment with ACEIs or Angiotensin II Receptor Blockers (ARBs).

PMID- 15253478
TI  - Physiological and hematological responses to cold exposure in young subjects.
AB  - BACKGROUND: In this study we have investigated the effect of cold exposure on
      young healthy subjects, with particular emphasis on the hematological system.
      STUDY DESIGN: The lightly clothed subjects were seated in a thermally controlled
      climatic chamber for three hours. METHODS: One group (control) was exposed to
      three hours at 28 degrees C, while the other group was first exposed to one hour
      at 28 degrees C, and then two hours of decreasing temperature, ending at 6
      degrees C. Mean body temperature decreased, blood pressure increased, and
      metabolism increased by 60% in the cold exposure group compared to the control
      group. Blood samples were taken through an arterial catheter every hour during
      the exposure, one hour before and 1.5, 3 and 25 hours after the exposure.
      RESULTS: Red blood cell counts increased, due to hemo-concentration. In the cold
      neutrophil counts did not increase during the day, but were stable at a lower
      level compared to the controls. CONCLUSIONS: It is suggested that the cold
      induced decrease in neutrophil count is caused by an activation and increased
      adhesion of the neutrophils to the endothelial wall. This finding is supported by
      the cold exposure-induced increases in IL-8 and Thromboxane B2 in LPS-stimulated
      blood, and an increase in the plasma concentration of P-selectin.

PMID- 15253479
TI  - Spirometry values in adults in northern Finland.
AB  - OBJECTIVES: If reference values do not accurately reflect the distribution of
      lung function in the population, the interpretation of spirometry results may be
      incorrect. Differences in lung function exist between populations, which supports
      the use of local reference values. In Finland, the national reference values for
      spirometry are currently in use. The aim of this study was to assess the
      correlation between measured spirometric values from healthy adults and the
      reference values used in Finland. METHODS: In the present population-based study,
      spirometry results were assessed in healthy adults aged 21 to 70 years in
      northern Finland. After exclusions for any chronic pulmonary disease or symptom,
      206 men and 215 women remained in the group. We calculated regression equations
      for spirometric reference values in adults and compared these with European
      recommendations, and with the reference values currently used in Finland.
      RESULTS: These comparisons revealed large differences. The linear models do not
      take into account the physiological changes in both young and old adults and,
      thus, the reference values calculated according to the European recommendations
      differed from the real measured results at both ends of the 20- to 70-year age
      scale. Moreover, values from the logarithmic Finnish reference equations also
      diverged from our measurements; the differences were largest in subjects younger
      than 30, and in elderly men. CONCLUSION: Differences between populations and
      reference equations make international comparisons difficult, and divergence
      between reference values and real results may lead to incorrect clinical
      interpretation.

PMID- 15253480
TI  - Winter swimming improves general well-being.
AB  - OBJECTIVES: This study deals with the effects of regular winter swimming on the
      mood of the swimmers. METHODS: Profile of Mood State (POMS) and OIRE
      questionnaires were completed before (October) and after (January) the four-month
      winter swimming period. RESULTS: In the beginning, there were no significant
      differences in the mood states and subjective feelings between the swimmers and
      the controls. The swimmers had more diseases (about 50%) diagnosed by a
      physician. Tension, fatigue, memory and mood negative state points in the
      swimmers significantly decreased with the duration of the swimming period. After
      four months, the swimmers felt themselves to be more energetic, active and brisk
      than the controls. Vigour-activity scores were significantly greater (p < 0.05).
      All swimmers who suffered from rheumatism, fibromyalgia, or asthma, reported that
      winter swimming had relieved pains. CONCLUSION: Improvement of general well-being
      is thus a benefit induced by regular winter swimming.

PMID- 15253481
TI  - Chromaticity of daylight: is the spectral composition of daylight an aetiological
      element in winter depression?
AB  - OBJECTIVES: Surveys on winter depression in Iceland indicate a significantly
      lower prevalence rate of winter SAD than expected according to Iceland's
      latitude. Research into daylight availability in Iceland failed to reveal factors
      contributing to higher average daylight availability than predicted by latitude.
      In view of the well-known healing effects of bright light treatment, we propose
      that properties of daylight other than daylight availability may ease the
      symptoms of winter depression. METHOD: We analysed the spectral composition of
      daylight in Iceland as expressed by its chromaticity and assessed its seasonal
      and diurnal variations. The colorimetric properties of daylight during the year
      1998 are dealt with in detail. Perception of daylight is modelled, applying the
      chromaticity model of MacLeod and Boynton along with environmental data on
      spectral irradiance recorded on location at 64 degrees 8.8' N and 21 degrees
      55.8' W in Reykjavik, Iceland, and recently published data on cone fundamentals
      by Stockman and Sharpe. RESULTS: The main finding is that blue hue dominates the
      colour of the sky, with high correlated colour temperature, without significant
      seasonal variations. Diurnal variations are, however, observed. Furthermore,
      significant deviation from 'standard' sky is detected. CONCLUSIONS: It is not
      known whether the observed chromaticity of daylight is a significant factor in
      explaining the unexpectedly low prevalence rate of seasonal affective disorder in
      Iceland.

PMID- 15253482
TI  - Incidence of psychiatric disorders after extended residence in Antarctica.
AB  - OBJECTIVES: The incidence of psychiatric disorders and depressive symptoms was
      examined in a cohort of American men and women who spent an austral winter at two
      different research stations in Antarctica to determine whether extended residence
      of nonindigenous inhabitants in a polar region is associated with psychiatric
      morbidity. STUDY DESIGN: Debriefings interviews with 220 men and 93 women were
      conducted by 3 psychiatrists and 1 clinical psychologist at McMurdo Station and
      South Pole Station at the end of the austral winter between 1994 and 1997.
      Crewmembers were assigned a DSM-IV diagnosis if they satisfied diagnostic
      criteria. Debriefed crewmembers also completed the Structured Interview Guide for
      the Hamilton Depression Inventory-Seasonal Affective Disorders version (SIGH
      SAD). RESULTS: Thirty-nine (12.5%) crewmembers presented with symptoms that met
      the criteria for one or more DSM-IV disorders. After weighting the prevalence to
      account for the low participation rate of civilian personnel, the incidence of
      DSM-IV disorders was 5.2%. Mood disorders were the most common diagnoses,
      accounting for 30.2% of all diagnoses, followed by adjustment disorders (27.9%),
      sleep-related disorders (20.9%), personality disorders (11.6%), and substance
      related disorders (9.3%). Depressive symptoms as measured by the SAD-SIGH were
      significantly associated with female gender, military occupation, station, year
      of expedition, and DSM-IV diagnosis. CONCLUSION: Differences in the distribution
      of symptoms and diagnoses by demographic and expedition characteristics suggests
      that the social environment may be a more powerful determinant than the physical
      environment of psychiatric disorders in a polar region.

PMID- 15253483
TI  - Elements in placenta and pregnancy outcome in arctic and subarctic areas.
AB  - OBJECTIVES: This paper describes a comprehensive assessment of the association of
      concentrations of essential and toxic elements in maternal and neonatal body
      fluids and the placenta as predictors of birth weight and newborn body mass index
      (BMIC) for deliveries in northern Norway and Russia. STUDY DESIGN: A prospective
      cross-sectional study of delivering women and their outcomes from different
      locations in Russian and Norwegian arctic and sub-arctic areas. METHODS: Life
      style information, blood, urine and placenta specimens were collected for 50
      consecutive mother-infant pairs from hospital delivery departments in a total of
      six communities located in Finnmark, Norway, or the western arctic/subarctic
      regions of Russia. Questionnaire information was collected by individual
      interviews performed by trained health personnel. Pregnancy outcomes were
      verified by consulting medical records. Cadmium, copper, iron (as ferritin),
      nickel, lead, selenium and zinc were measured in maternal blood, serum or
      maternal urine: and in cord blood, or neonatal urine and placental tissue.
      Univariate and multivariate linear regression analysis and ANOVA were employed to
      explore associations between these clinical chemistry outcomes and birth weight
      and BMIC. RESULTS: A number of significant relationships were evident between:
      placental and maternal blood cadmium (p < 0.005); cord and maternal blood lead (p
      < 0.001); placental and maternal blood lead (p < 0.001); placental and cord-blood
      lead (p < 0.001); placental and maternal serum, or blood, selenium (p < 0.001);
      and placental and maternal serum copper (p < 0.001). Maternal body mass index
      (BMI), maternal age, placental lead, or maternal blood lead, and smoking were
      retained as predictors of birth weight and BMIC in the multivariate modelling.
      Birth weights in both countries were normally distributed. CONCLUSIONS: Maternal
      age and BMI as positive predictors of birth weight, and cigarette smoking and
      lead exposure as negative determinants, are discussed in terms of established
      evidence and recognized confounders, including maternal genetic factors, socio
      economic status, socio-political change, life-style issues, prenatal care and
      nutrition. It is recommended that future work in societies undergoing socio
      economic transition might best focus on preventive measures to improve neonatal
      health and development.

PMID- 15253484
TI  - [Cutis laxa syndrome. Case report].
AB  - INTRODUCTION: Cutis laxa is a heterogeneous group of connective tissue
      disorders,characterized by loose skin and variable systemic involvement. The
      characteristic symptomatological pattern is resulting from paucity of elastic
      fibers. CASE REPORT: A 4 year-old boy with a congenital cutis laxa was sent by
      his pediatrician for ophthalmic examination. His examination revealed an
      ectropion of the right lower lid and an entropion of the left lower lid. His
      general physical examination showed multiple visceral involvement, with inguino
      scrotal hernia, multiple dental caries and severe pulmonary emphysema responsible
      for death two weeks after. DISCUSSION: Cutis laxa is an extremely rare group of
      disorders. Congenital and acquired varieties have been described. The association
      of ocular anomalies has been described in the autosomal recessive form. Through
      this case report we shall discuss the ophthalmological signs of this disease as
      well as its clinical and genetic manifestation and its physiopathology.

PMID- 15253485
TI  - Contact allergic reactions on the eyes and eyelids.
AB  - PURPOSE: To determine the most important causes of contact allergic reactions on
      the eyes and eyelids. PATIENTS AND METHODS: This retrospective study provides an
      analysis of patch-test results obtained in a population of 1554 patients
      suffering from conjunctivitis and/or dermatitis on the eyelids, out of a total
      population of 9035 patients investigated for contact allergy between January 1990
      and October 2003. If indicated, also prick testing with a latex extract was
      performed. RESULTS: 864 (56%) of the patients with eye- and/or eyelid-involvement
      presented with a positive reaction to at least one of the contact allergens
      tested. The main sensitisation sources were topical pharmaceutical products
      (antibiotics, corticosteroids), cosmetics (fragrance components, preservatives,
      emulsifiers, hair-care and nail products), metals (nickel), rubber derivatives,
      resins (e.g. epoxy resin), and plants. Also latex-allergy (immediate-type
      sensitivity presenting as a contact-urticaria syndrome) was a frequent finding in
      such patients. CONCLUSION: Contact allergy is a common cause of eyelid dermatitis
      in particular and the allergens may reach the skin in many different ways.

PMID- 15253487
TI  - Miscalibration and severe complications after diode laser cyclophotocoagulation:
      two case reports.
AB  - Because two similar transscleral cyclophotocoagulation diode lasers with
      identical power & duration settings induced significantly different postoperative
      inflammation, we wanted to compare the real output of both lasers. Using a
      Power/Energy Meter (Fieldmaster) we compared the output of the two lasers (the
      Iridis [Quantel Medical] and the Iris Medical [OcuLight SLx]) at different energy
      levels. At a setting of 600, 1000, 1400, 1700, 2000 and 2500 mW, the measured
      output for the Iridis and Iris Medical diode laser were respectively 685 and 400
      mW, 970 and 650 mW, 1470 and 875 mW, 1700 and 1000 mW, and 1990 compared to 1000
      mW. On the average the output of the Iridis laser was correct and the output of
      the Iris Medical laser was 40% lower than the setting. Overtreatment and severe
      complications occurred with the Iridis laser because the manufacturer recommended
      using wrong power settings based on the Iris Medical laser, which was
      undercalibrated. The calibration of cyclophotocoagulation diode lasers should be
      performed prior to use when changing to a new device and whenever over- or
      undertreatment is observed.

PMID- 15253486
TI  - LASIK and arcuate incisions for the treatment of post-penetrating keratoplasty
      anisometropia and/or astigmatism.
AB  - PURPOSE: To study the efficacy of Laser In Situ Keratomileusis (LASIK) and
      Arcuate Keratotomy (AK) for the treatment of anisometropia and/or astigmatism
      after Penetrating Keratoplasty (PKP) in an attempt to optimize binocular vision.
      MATERIAL AND METHODS: Correction of post-PKP anisometropia and/or astigmatism was
      considered only when stable refraction was achieved for at least 6 months. Four
      eyes were treated for anisometropia and astigmatism using the LASIK technique (IN
      PRO Gauss Excimer Laser and SKBM Microkeratome). Five eyes were treated with AK
      to correct post-PKP astigmatism only. The results were evaluated using the
      following parameters: uncorrected visual acuity (UCVA), best subjective spectacle
      correction (BSC-VA), corneal uniformity (CU) index and predictive corneal (PC)
      acuity from the Holladay Diagnostic Summary (HDS) analysis. RESULTS: Post-PKP
      anisometropia and astigmatism were treated successfully after primary LASIK in
      three out of the four cases. One eye needed an additional diode thermal
      keratoplasty (DTK). Astigmatism post-PKP was treated successfully after primary
      AK in four of the five cases. One eye needed an additional LASIK. CONCLUSION: AK
      can be used successfully in cases of low-grade post-PKP astigmatism. LASIK gives
      better results in cases of post-PKP anisometropia and astigmatism. In order to
      affine the final results a combination with other refractive techniques such as
      DTK can be proposed. CU index and PC acuity (EyeSys-HDS analysis) are poor
      predictive parameters for visual outcome in cases of irregular corneal surfaces
      as it is often the case after PKP.

PMID- 15253488
TI  - [Enucleations: epidemiologic investigation in Morocco. presentation of 183
      cases].
AB  - INTRODUCTION: The authors report the results of an epidemiological study
      concerning 183 enucleated eyeballs. MATERIAL AND METHODS: [corrected] The study
      is realized over a 12-year period (1988-2000) in the department of Ophthalmology
      "B" (University Hospital--Rabat) on 183 enucleated eyes, only 90% having an
      histological examination. RESULTS: The aetiologies are: trauma (40%), malignant
      tumours (30%), atrophies and glaucoma (17%), panophthalmitis (9%) and corneal
      lesions (4%). The authors compare their results with those of the literature.
      CONCLUSION: The causes of enucleation are the same throughout the world. The
      frequency has lately decreased due to the development of early diagnosis and to
      the use of more conservative treatments.

PMID- 15253489
TI  - [Etiology of posterior uveitis and panuveitis at the Central University Hospital
      in Monastir].
AB  - The authors conducted a retrospective analysis of 245 patients with posterior
      uveitis or panuveitis in order to determine their etiologies and collect some
      epidemiological data. A specific diagnosis was made in 80.4%. Behcet's disease
      (22.4%), toxoplasmosis (22%), and Vogt-Koyanagi-Harada syndrome (9%) were the
      most common causes of posterior uveitis or panuveitis. No case of confirmed
      sarcoidosis was found in our series.

PMID- 15253490
TI  - Refractory ocular hypertension secondary to intravitreal injection of
      triamcinolone acetonide.
AB  - PURPOSE: to report a case of severe ocular hypertension occurring as a
      complication after a single intravitreal injection of triamcinolone acetonide for
      the treatment of a diabetic cystoid macular edema. METHODS: interventional case
      report. RESULTS: a 63-year-old pseudophakic diabetic woman developed a severe and
      relatively sudden IOP increase to 50 mm Hg one month after receiving a single 4
      mg intravitreal injection of triamcinolone acetonide for a chronic progressive
      macular cystoid edema. Previously the patient who did not develop corticosteroid
      induced glaucoma secondary to her cataract surgery was treated with topical beta
      blockers for a mild chronic bilateral ocular hypertension. A deep sclerectomy had
      to be performed in emergency to avoid optic nerve damage and allowed to
      successfully control the IOP with a 5 month follow-up. Concomitantly visual
      acuity could be increased from 0.05 before the intravitreal injection to 0.4.
      CONCLUSIONS: Although unfrequent in the literature, this observation confirms the
      risk of occurrence of a severe ocular hypertension after intravitreal injection
      of triamcinolone. A close monitoring of IOP is mandatory after intravitreal
      injection, especially in patients with altered trabecular function. This
      potentially devastating complication has to be weighed up with the benefices of
      intravitreal injection of triamcinolone for improving visual acuity in patients
      with clinically significant diabetic macular edema.

PMID- 15253491
TI  - Angel's trumpet (Brugmansia arborea) and mydriasis in a child--a case report.
AB  - We report a case of anisocoria in a 6-year old child who felt out of an
      inflatable swimming pool in the garden. After instillation of pilocarpine 1% the
      dilated pupil constricted, which is an important clinical sign associated with
      intracranial trauma. There was evidence of exposure to angel's trumpet
      (Brugmansia arborea), a plant known to contain anticholinergic substances. As the
      results of further neurological examination turned out to be normal, we believe
      the mydriasis was due to an accidental exposure to angel's trumpet. The time lag
      between exposure and presentation at the emergency room, the probably low volume
      of the plant extract in the eye and the unpredictable concentration of alkaloids
      in the plant, can influence and question the reliability of the pilocarpine test
      in this case.

PMID- 15253492
TI  - [Association of choroidal coloboma, congenital hypertrophy of retinal pigmented
      epithelium and familial adenomatous polyposis: case report].
AB  - INTRODUCTION: The choroidal coloboma is a congenital malformation that results
      from an anomaly of the embryonic fissure. This anomaly is frequently associated
      to numerous ocular and systemic anomalies, but rarely to familial adenomatous
      polyposis. CASE REPORT: We report a 12 years-old boy, who consulted for severe
      visual impairment of the right eye. The clinical examination revealed a coloboma
      of the iris and choroid and numerous lesions of congenital hypertrophy of the
      retinal pigmentary epithelium while exploration of the digestive tract revealed
      the presence of familial adenomatous polyposis. DISCUSSION: We discuss the
      physiopathological mechanisms of this rare case, associating on one hand a
      coloboma of iris and choroid and on the other hand a congenital hypertrophy of
      the retinal pigment epithelium and a familial adenomatous polyposis. To the best
      of our knowledge this association has never been described before. We also
      emphasize the importance of an ophthalmologic examination for screening familial
      adenomatous polyposis in a subject at risk.

PMID- 15253493
TI  - [Primary intention to treat intraocular metallic foreign body using radical
      vitrectomy].
AB  - In order to compare the prognosis of eyes with a metallic intraocular foreign
      body withdrawn with a complete versus incomplete vitrectomy, our retrospective
      study analyzes the functional result and complications in a consecutive series of
      13 eyes, depending on whether the vitrectomy included or not the removal of the
      posterior hyaloid and the shaving of the vitreous base. Six eyes underwent one of
      these 2 surgical maneuvers. Three eyes underwent both of these 2 maneuvers and
      ended up with 10/10 visual acuity and no complications or reoperations. Among the
      4 eyes that did not benefit from any of these 2 maneuvers, 3 required a
      vitrectomy revision because of a retinal detachment or a secondary hemorrhage. We
      conclude that a radical vitrectomy could improve the prognosis of eyes with an
      intraocular metallic foreign body.

PMID- 15253494
TI  - Comparison of optical coherence reflectometry and ultrasound central corneal
      pachymetry.
AB  - In 50 eyes of 25 patients we prospectively measured the central corneal thickness
      (CCT) comparing the OLCR (Optical Low Coherence Reflectometry) pachymeter with
      the contact ultrasound pachymeter. The OLCR system was mounted on to a Haag
      Streit slit lamp. Every single measurement was the result of 5 scans. With the
      contact ultrasound Sonomed pachymeter we performed 5 separate measurements and
      calculated the mean. The correlation between the two measurements was excellent
      (r = 0.99). The mean standard deviation (SD) of the measurements taken with the
      non-contact OLCR pachymeter was significantly lower than with the contact
      ultrasound pachymeter, 0.49 microm and 4.71 microm respectively (p < 0.01). The
      variability of the CCT measurements taken with the non-contact OLCR pachymeter is
      significantly lower than the variability of the CCT measurements taken with the
      contact ultrasound pachymetry.

PMID- 15253495
TI  - Ecological rucksacks and waste management systems.

PMID- 15253496
TI  - Towards a cleaner production in developing countries: a case study in a Chilean
      tannery.
AB  - A Chilean leather tanning industry (tannery) was studied in terms of input/output
      (I/O) analysis of beamhouse, tanyard and retanning processes. The physical
      chemical characterization of 19 streams were investigated. Streams from the
      beamhouse process and some streams from the retanning process were found to have
      high organic contents ranging from 2.5 to 18.1 g COD L(-1). The pH ranged between
      3.45 and 12.28. Sulphur was found in most of the streams whereas chromium was
      detected in two wastewaters from the tanyard and in seven streams from the
      retanning process. Pollution prevention opportunities were evaluated and an
      appropriate treatment strategy was proposed. The main emphasis was on determining
      waste reduction measures that can be easily implemented and are not particularly
      expensive. Measures for reduction at source were proposed to reduce water and
      chemicals consumption and wastewater pollution. A so-called S(index) strategy was
      used to evaluate proposals on segregation and specific treatment of the main
      chromium- and sulphur-containing wastewaters. It was suggested that some streams
      may be re-used, but it is necessary to apply anaerobic or aerobic treatment
      first, depending on their organic load. Solid wastes were also evaluated and a
      proposal for their reduction and disposal was made.

PMID- 15253497
TI  - Sampling household waste at source: lessons learnt in Gaborone.
AB  - Municipal solid waste (MSW) quantity and composition analysis is fundamental for
      the planning of municipal waste management services. The purpose of this paper is
      to report the results and experiences of sampling household waste at the source
      of generation in Gaborone, Botswana. The average generation rate, in kg capita(
      1) day(-1), and percentages of various components of waste in Gaborone were
      determined using a statistically designed household sampling survey. The survey
      covered 47 households with different socio-economic characteristics over 21 days
      with 893 samples obtained. The results showed that the average waste generation
      rate for Gaborone was 0.33 kg capita(-1) day(-1). Contrary to common belief, the
      waste generation rate measured as in weight units was found not be directly
      related to household income. However, the packaging fractions of plastic and
      paper measured as volume had a direct relationship with household income. Across
      all income groups, the putrescible waste fraction constituted the highest
      proportion of the waste stream at approximately 68%. The main general conclusion
      is on the importance of practical considerations. As much as statistically
      designed sampling procedures provide a useful means of estimating the quantity
      and composition of household waste at source of generation, there are some
      practical issues that should be carefully considered during sampling to improve
      the accuracy and relevance of the results.

PMID- 15253498
TI  - The effect of advanced oxidation processes on leachate biodegradation in
      recycling lysimeters.
AB  - Landfill processes were simulated in laboratory-scale bioreactors--lysimeters.
      The changes in leachate characteristics as well as the influence of advanced
      oxidation processes (AOPs) on the processes taking place in the sanitary landfill
      were investigated. Lysimeters were filled with material simulating municipal
      waste in the city of Lodz, Poland. Compost in the amount of 30% w/w and the
      methanogens inoculum were added in order to enhance development of a methanogenic
      phase. The leachate produced in lysimeters was recirculated. In order to
      investigate the influence of AOPs implementation on processes taking place in
      landfills two runs in lysimeters were performed, each lasting about 250 days. The
      leachate composition and biogas composition and production changes showed trends
      that confirmed that the bench-scale lysimeters appeared suitable to simulate
      processes taking place in the landfill. The application of AOPs to the leachate
      recirculated into the lysimeters did not bring about unequivocally positive
      effects. The ozonation of the leachate, implemented at the beginning of the
      methanogenic phase, caused slight acceleration (about 2 weeks) of the
      biodegradation, whereas employment of H2O2/UV led to the inhibition of anaerobic
      processes.

PMID- 15253499
TI  - Oyster shell as substitute for aggregate in mortar.
AB  - Enormous amounts of oyster shell waste have been illegally disposed of at oyster
      farm sites along the southern coast of Korea. In this study to evaluate the
      possibility of recycling this waste for use as a construction material, the
      mechanical characteristics of pulverized oyster shell were investigated in terms
      of its potential utilization as a substitute for the aggregates used in mortar.
      The unconfined compressive strengths of various soil mortar specimens, with
      varying blending ratios of cement, water and oyster shell, were evaluated by
      performing unconfined compression tests, and the results were compared with the
      strengths of normal cement mortar made with sand. In addition, the effect of
      organic chemicals on the hardening of concrete was evaluated by preparing ethyl
      benzene-mixed mortar specimens. The long-term strength improvement resulting from
      the addition of fly ash was also examined by performing unconfined compression
      tests on specimens with fly-ash content. There was no significant reduction in
      the compressive strength of the mortars containing small oyster shell particles
      instead of sand. From these test data, the possible application of oyster shells
      in construction materials could be verified, and the change in the strength
      parameters according to the presence of organic compounds was also evaluated.

PMID- 15253500
TI  - Detection and enumeration of Cryptosporidium sp. oocysts in sewage sludge samples
      from the city of Florianopolis (Brazil) by using immunomagnetic separation
      combined with indirect immunofluorescence assay.
AB  - In the last few decades, agricultural reclamation of sewage sludge has increased
      in many countries. However, this practice must be adopted under recommended
      conditions to limit the risks associated with the presence of potential
      pathogens, including protozoan parasites such as Cryptosporidium. In the present
      work, we evaluated immunomagnetic separation (IMS) combined with an indirect
      immunofluorescence assay (IFA) in order to detect Cryptosporidium oocysts in
      sewage sludge samples obtained from the Municipal Wastewater Treatment Plant
      (MWTP) operating in the city of Florianopolis, State of Santa Catarina, Brazil.
      Integrated application of spontaneous sludge sedimentation and centrifugation of
      the supernatant, purification and concentration of oocysts through immunomagnetic
      separation as well as detection and quantification by means of indirect
      immunofluorescence using highly specific monoclonal antibodies, proved to be an
      effective multiple-analysis tool for monitoring the presence of Cryptosporidium
      oocysts in urban sewage sludge samples. Among 27 samples collected from MWTP, 20
      (74.07%) were positive for Cryptosporidium sp. The efficiency of recovery by
      using the internal control ColorSeed (Biotechnology Frontiers Inc., Sydney, NSW,
      Australia) was medially 39.96 +/- 11.20%. Actually, oocysts were recovered from
      100% of the positive samples tested and the number of Cryptosporidium oocysts
      found in the samples ranged from one to four. These results demonstrated a high
      recovery rate of Cryptosporidium oocysts in sewage sludge samples by using IMS
      IFA analysis. In conclusion, such an approach can be applied to monitor the
      presence of the parasite and to determine the potential contamination of sludge
      destined for soil application.

PMID- 15253501
TI  - Process control in municipal solid waste incinerators: survey and assessment.
AB  - As there is only rare and scattered published information about the process
      control in industrial incineration facilities for municipal solid waste (MSW), a
      survey of the literature has been supplemented by a number of waste incineration
      site visits in Belgium and The Netherlands, in order to make a realistic
      assessment of the current status of technology in the area. Owing to the
      commercial character, and therefore, the confidentiality restrictions imposed by
      plant builders and many of the operators, much of the information collected has
      either to be presented in a generalized manner, and in any case anonymously. The
      survey was focused on four major issues: process control strategy, process
      control systems, monitors used for process control and finally the correlation
      between the 850 degrees C/2 s rule in the European waste incineration directive
      and integrated process control. The process control strategies range from
      reaching good and stable emissions at the stack to stabilizing and maximizing the
      energy output from the process. The main indicator to be monitored, in cases in
      which the focus is controlling emissions, is the oxygen content in the stack.
      Keeping the oxygen concentration in a determined range (usually between 8 and 12
      vol.%) ensures stable and tolerated concentrations of the gaseous emissions. In
      the case for which stabilization of energy production is the principal aim, the
      main controlled parameter is the steam temperature and flow-rate, which is
      usually related to the fuel energetic input. A lot of other parameters are used
      as alarm criteria, the most common of which is the carbon monoxide concentration.
      The process control systems used most commonly feature partially automated
      classical proportional integral derivative (PID) controllers. New and innovative
      process control systems, such as fuzzy-logic control systems, are still unknown
      to most plant managers while their performance is reported to be unsatisfactory
      in plants in which such systems have been tested or are in use. Monitoring
      components used in process control are still based on classical tools such as
      thermocouples. The use of modern and more reliable sensors is very limited due to
      the high initial investment cost or simply the fear of using non-standard
      technologies. Complying with the 850 degrees C/2 s rule in the European waste
      incineration directive generally is seen to be a handicap for the process
      control, either in terms of cost, or flexibility of reaction, or both,
      particularly in old incineration facilities where such restrictions were not
      planned in the design.

PMID- 15253502
TI  - Gas permeability and tortuosity for packed layers of processed municipal solid
      wastes and incinerator residue.
AB  - To make a proper evaluation of gas component movement inside a landfill site, it
      is important to investigate the different parameters related to gas flow. In this
      work gas-filled porosity, intrinsic permeability, tortuosity and equivalent pore
      radius were determined for various packed wastes, such as incineration ash,
      shredded bulky waste and shredded incombustible waste. These parameters were
      measured/inferred for samples packed in a column and exposed to a controlled gas
      flow. The effect of waste conditions, especially the moisture content, on these
      parameters was also investigated. The intrinsic permeability of such packed
      wastes was generally in the order of 10(-10) to 10(-9) m2, except for some ash
      that was one to two orders lower. The tortuosity of waste layer was greater than
      that of a particulate material and ranged between 2 and 10. The equivalent pore
      radius was generally in the order of 10(-4) m, which means that gas diffusion is
      still ordinary in such packed waste layer. The obtained results will be utilized
      when simulating gas flow inside a landfill site for biogas extraction or site
      aeration.

PMID- 15253503
TI  - Operational and meteorological influence on the utilized biogas composition at
      the Barycz landfill site in Cracow, Poland.
AB  - The aim of the present investigation was to determine time variation of biogas
      composition at the gas collection network on the 'Barycz' landfill site in
      Cracow, Poland, as well as the influence of operational and meteorological
      conditions on the biogas composition. The study of biogas composition at selected
      gas wells and gas collectors was conducted using a portable IR landfill gas
      analyser. The methane concentration in biogas on the part of the landfill site
      currently in operation varied in the range 59-63% vol. and on the reclaimed part
      of the landfill, in the range 42-62% vol. It was found that biogas composition is
      significantly affected by operational conditions and meteorological parameters.
      For example, methane concentrations were more constant when the pressure in the
      installation was above the ambient atmosphere than when it was below, where
      fluctuations of 15% vol. were seen. Low air temperature, high precipitation and
      high atmospheric pressure, which lower the permeability of the outer layer of the
      landfill, result in higher quality of the biogas getting to the gas collection
      system.

PMID- 15253504
TI  - Tradable permits without legislative targets: a review of the potential for a
      permit scheme for sterilized clinical waste in the UK.
AB  - Tradable-permit schemes are becoming an increasingly popular technique for
      encouraging materials recovery and the diversion of waste from landfill. Such
      schemes operate using various forms of market-based trading of waste permits
      between polluters but usually rely on mandatory recycling targets to provide an
      incentive for trading. Using the UK's Packaging Recovery Note (PRN) scheme as a
      template, this paper examines the potential for permit trading where mandatory
      targets are absent and schemes must be driven solely by the financial benefits of
      reduced landfill costs and permit/material sales. The case examined is sterilized
      clinical waste, which has considerable recycling potential but suffers from
      health concerns and a poor public image. Interviews with healthcare and waste
      management representatives indicate that although elements of the PRN scheme
      might prove appropriate for encouraging materials recovery, the absence of
      government targets and uncertain end markets for sterilized clinical waste
      present major obstacles to trading. Alternative incentives would therefore be
      required to catalyse schemes and develop recycling infrastructure. In the final
      analysis, thermal processing may be a more practical alternative to landfill than
      materials recovery for this particular waste stream.

PMID- 15253505
TI  - Management of packaging waste in Poland--development agenda and accession to the
      EU.
AB  - In recent years the issue of the municipal waste in Poland has become
      increasingly topical, with a considerable rise in the waste generation, much of
      which can be attributed to a boom in product packaging (mainly plastic). The
      annual production of plastics packaging has been constantly increasing over the
      last 20 to 30 years, and now exceeds 3.7 million tons. Due to a lack of
      processing technologies and poorly developed selective segregation system,
      packaging waste is still treated as a part of the municipal solid waste (MSW)
      stream, most of which is landfilled. As a result of Poland's access to the
      European Union, previous legal regulations governing municipal waste management
      have been harmonized with those binding on the member countries. One of the main
      changes, the most revolutionary one, is to make entrepreneurs liable for
      environmental risks resulting from the introduction of packaging to the market,
      and for its recycling. In practice, all entrepreneurs are to ensure recovery, and
      recycling, of used packaging from products introduced to the market at the
      required level. In recent year, the required recycling levels were fulfilled for
      all types of materials but mainly by large institutions using grouped and
      transport packaging waste for that matter. Household packaging gathered in the
      selective segregation system at the municipalities was practically left alone.
      This paper is an attempt to describe the system and assess the first year of
      functioning of the new, revamped system of packaging waste management in Poland.
      Recommendations are made relating to those features that need to be included in
      packaging waste management systems in order to maximize their sustainability and
      harmonization with the EU legal system.

PMID- 15253506
TI  - Doing anger differently: a group percussion therapy for angry adolescent boys.
AB  - This paper describes Doing Anger Differently (DAD), a group treatment for young
      adolescent boys with high levels of anger. The approach is school-based, 10 weeks
      long, and utilizes music in the form of percussion to engage this difficult to
      treat population into treatment and to represent the experience of anger. A tri
      level intervention is described: the experience of anger and its influence on
      action; the formation of meaning and identity resulting from anger and
      aggression; and the emphasis on group work and the interpersonal basis of anger.
      Techniques used throughout the group are discussed and illustrative case
      vignettes are provided.

PMID- 15253507
TI  - Group therapy for depressed elderly women.
AB  - We describe and evaluate a group therapy program targeting depression among
      elderly residents (N=303) of subsidized high-rise apartments in Nashville, TN.
      This eclectic program was comprised of 12 sessions (a total of 24 hours) that
      included modules on exercise and preventive health behaviors, cognitive and re
      motivation therapy, reminiscence and grief therapy, and social skills
      development. Our multivariate regression analyses of pre-post measures using the
      Geriatric Depression Scale (GDS) showed that the effects of the group therapy
      varied by race, age, and level of initial depression among the participants. The
      program was effective in reducing depression, but only among Caucasian women who
      reported at least moderate depression prior to the program, and it yielded
      greater benefits for women between 55 and 75 years of age.

PMID- 15253508
TI  - Truth and falsity in group.
AB  - The universal tension and juxtaposition between truth seeking and truth evasion
      are explored in a contemporary relational context, drawing on Bion 's later ideas
      on group. Bion's key idea of "psi," or psychic evasiveness, refocuses group
      theory, supplementing intra- and inter-psychic perspectives with sociopolitical
      analysis. To some extent the psychotherapy group exists as a political
      "Establishment" and thus corresponds to psi. Using three illustrative case
      examples, the nature and nurture of truth evasion is considered, along with the
      purposes it serves and the forms it may take. The therapist must maintain a
      disruptive-creative influence on group process, but like other group members, he
      or she instead may accept and promote falsity. Whereas the therapist ensures the
      integrity of the culture, the members, and not solely the therapist, break up old
      relational patterns and experiment with new ones. Dynamic, evolving groups aid
      the leader in life-affirming truth-seeking, eventually challenging establishment
      tendencies and exposing falsity.

PMID- 15253509
TI  - Group interventions for patients with cancer and HIV disease: Part III.
      Moderating variables and mechanisms of action.
AB  - Growing evidence supports the value of group interventions for individuals who
      are at risk for or have developed cancer or HIV disease. However, information is
      more limited concerning how these services can be delivered in an optimal manner,
      and what processes contribute to their benefits. Parts I and II of this review
      examined the efficacy of different interventions for individuals at different
      phases of illness, ranging from primary prevention to late-stage disease, in both
      psychosocial and biological domains. The current paper examines some of the
      factors other than phase of illness that might influence group treatment effects
      (e.g., intervention parameters, participant characteristics), and explores
      mechanisms of action.

PMID- 15253510
TI  - Reflections on the abuse of power, control and status in group therapy and group
      therapy training.

PMID- 15253511
TI  - Group psychotherapy and Parkinson's disease: when members and therapist share the
      diagnosis.
AB  - This report describes a psychosocial therapy group for Parkinson's patients,
      focusing on the therapeutic processes arising when group members and therapist
      share the diagnosis of Parkinson's disease. The paper explores the question,
      "What is the therapeutic effect on the group when the therapist suffers and
      displays the same illness as members of the group"? Countertransference issues
      are described.

PMID- 15253512
TI  - Group therapy for bipolar patients.

PMID- 15253513
TI  - Making public health improvement real: the vital role of systems research.

PMID- 15253514
TI  - A research agenda for public health workforce development.
AB  - In the past decades, public health research has focused on categorical rather
      than cross-cutting or systems issues. Little research has been carried out on the
      infrastructure required to support public health programs. This article describes
      the results of an interactive process to develop a research agenda for public
      health workforce development to inform all those with stakes in the public health
      system. This research is defined as a multidisciplinary field of inquiry, both
      basic and applied, that examines the workforce in terms of costs, quality,
      accessibility, delivery, organization, financing, and outcomes of public health
      services to increase knowledge and understanding of the relationships among
      workforce and structure, processes, and effects of public health services. A
      logic model and five priority research areas resulted from meetings of expert
      panels during 2000 to 2003. Innovative public and private partnerships will be
      required to advance cross-cutting and systems-focused research.

PMID- 15253515
TI  - Identifying dimensions of performance in local public health systems: results
      from the National Public Health Performance Standards Program.
AB  - This article uses data from the National Public Health Performance Standards
      Program to explore how the performance of essential public health services varies
      across communities and to identify underlying domains of activity that appear to
      drive variation in performance. Cross-sectional data were used from 315 local
      public health jurisdictions located within seven states that participated in the
      Performance Standards Program pilot tests between 1999 and 2001. Results
      demonstrate that local public health systems vary considerably in the extent to
      which they perform essential services and meet established performance standards.
      Factor analysis results indicate that four underlying domains of activity explain
      much of the variation observed in the individual performance measures, and that
      achieving performance standards for a single essential public health service
      often involves more than one underlying domain of activity. The findings suggest
      that composite measures constructed from the Performance Standards Program can
      assist public health decision makers in monitoring the performance of public
      health systems and identifying promising pathways for improving performance.

PMID- 15253516
TI  - Local public health agency capacity and its relationship to public health system
      performance.
AB  - he study described in this article identifies local public health agency capacity
      characteristics that are related to their local public health systems'
      performance scores on the CDC's National Public Health Performance Standards
      Program assessment instrument. Public health system performance scores from a
      test version of the National Public Health Performance Standards instrument (5b)
      from county and city/county jurisdictions in three states were matched to
      organizational capacity data from the 1997 National Association of County and
      City Health Officials profile of health departments, resulting in a sample of 152
      jurisdictions. Twenty-eight capacity variables from the profile and all 10 scores
      on the Essential Public Health Services plus the total performance score were
      analyzed in 11 separate multivariate regression models. Public health agency
      capacities in the areas of funding, organizational leadership, and certain
      nonprovider partnerships were found to be significantly related to public health
      system performance. Further study is needed to determine if these relationships
      between agency capacities and system performance are found, with data from other
      states now using the nationally released performance assessment instruments and
      with capacity measures that are more specific for evaluating public health system
      performance.

PMID- 15253517
TI  - Implementing the National Local Public Health System Performance Assessment:
      evaluation of a readiness process in Kentucky.
AB  - The objectives of the study described in this article were to test training and
      resource materials for preparing Kentucky public health agency staff to lead the
      National Local Public Health System Performance Assessment and to identify
      barriers encountered in implementation. Readiness supports provided to five
      Kentucky district and county health departments that led the system assessment
      process in 12 counties were evaluated using training pre- and posttests,
      performance assessment posttests, observations, and interviews. The training and
      materials provided in this study appeared to be the minimum needed for these
      Kentucky health departments. Training sequences need to allow time for
      independent study of assessment processes, and training in using and interpreting
      the assessment instrument should be included. Partner orientation materials
      targeted for nonpublic health partners would be useful. In Kentucky, barriers to
      completing the assessment included questions about its purpose and benefits and
      the lack of a self-identified local public health system. Formal training of
      health department staff, committed leadership, and adequate personnel resources
      can help overcome these barriers. The health departments that brought together
      system partners for the performance assessment considered it a valuable community
      building educational event.

PMID- 15253518
TI  - Public health preparedness and response capacity inventory validity study.
AB  - The Centers for Disease Control and Prevention's Public Health Practice Program
      Office has issued a Public Health Preparedness and Response Capacity Inventory to
      help state and local public health systems assess their progress towards
      achievement of the critical capacities and benchmarks specified in the federal
      Supplemental Funds for Public Health Preparedness and Response for Bioterrorism.
      The criterion validity of the capacity inventory was assessed by comparing
      selected state and local agency responses with documentation provided by the
      agencies to corroborate their answers. Content validity assessment took the form
      of a mailed survey that also identified the most important questions from the
      perspective of a separate set of state and local officials. Responses generally
      upheld the validity of the capacity inventory, although circumstantial threats to
      validity were identified in the testing process. The instrument's use has been
      reported to the Centers for Disease Control and Prevention by approximately half
      the states and over 800 local public health entities. An interactive electronic
      version includes a scoring mechanism that allows agencies to judge progress
      towards the critical capacities and benchmarks over time.

PMID- 15253519
TI  - The public health dashboard: a surveillance model for bioterrorism preparedness.
AB  - The City of Milwaukee Health Department piloted a short-term, near real-time
      syndromic surveillance and communication tool by using an existing secure
      regional Internet infrastructure. Voluntary, active syndromic case reporting by
      hospital Emergency Departments was combined with other data streams, including
      clinical laboratory reports of communicable disease, hospital emergency room
      diversions, ambulance runs, medical examiner reports of unusual or suspicious
      deaths, poison control and nursing hotline call volumes, and pharmacy over-the
      counter sales. These data were aggregated into a "Surveillance Dashboard" format
      that was used to communicate community syndromic health trends to hospitals,
      Emergency Departments, and other providers using a secure Internet technology.
      Emergency Departments at 8 area hospitals reported a total of 314 cases meeting
      syndromic criteria from 26,888 patient encounters. Participants were satisfied
      with data entry and communications. All participating Emergency Departments
      received e-mail and text pager alerts sent by the Milwaukee Health Department. No
      unexplained findings or suggestions of an early outbreak were reported through
      syndrome surveillance for the 4-week duration of the project. Similar
      surveillance and communications systems could provide multiple benefits to
      Emergency Department workflow and management, as well as to public health and
      emergency response.

PMID- 15253520
TI  - Public perceptions of quality care and provider profiling in New York:
      implications for improving quality care and public health.
AB  - Despite a growing emphasis on providing health care consumers with more
      information about quality care, useful and valid provider-specific information
      often has not been available to the public or has been underutilized. To assess
      this issue in New York State, random telephone surveys were conducted in
      September 2002 and March 2003, respectively, of 1,001 and 500 English- or Spanish
      speaking persons, 18 years or older. Results indicated that 33% of New Yorkers
      were very concerned about the quality of care, with African Americans being
      particularly concerned. Less than half of the respondents recalled hearing or
      seeing information about health care quality in the past year and less than 20%
      actually used this information in medical decision making. African Americans were
      the least likely to recall receiving or being exposed to quality-related
      information, whereas women and more educated adults were the most likely to
      report being exposed. Furthermore, New Yorkers received quality information from
      multiple sources, with about 20% saying that they obtained information about
      physician and hospital quality from media (eg, newspaper) and nonmedia (eg,
      recommendation by family member) sources. Evaluations of different kinds of
      information suggested that some types (eg, whether or not a doctor is board
      certified) carried more weight in health care decision making than other types
      (eg, government ratings). Unexpectedly, those who used information to make health
      care decisions were more likely to have reported experiencing a medical error in
      the household. Finally, in the 6-month follow-up survey, concerns about the
      quality of care in the state remained about the same, while fears of terrorism
      decreased and preparations for future terrorist attacks increased. In the survey,
      few major differences were found in results based on payer status (eg, private
      insurance versus Medicaid/no insurance). These findings have implications for
      both the private and public health care sectors. Specifically, they suggest that
      greater access to and use of provider-specific health care information by the
      public is a viable way to improve quality, particularly if health care
      professionals support the public use of these data.

PMID- 15253521
TI  - Collaborative partnerships at the state level: promoting systems changes in
      public health infrastructure.
AB  - Reforms in the public health infrastructure such as those called for in recent
      Institute of Medicine reports require stakeholder engagement on different levels
      than traditional grass-roots community work. The Turning Point Initiative, funded
      by The Robert Wood Johnson Foundation, involves 21 state-wide partnerships
      established for systems change and focused in specific areas of public health
      innovation and policy development. These partnerships represent a different model
      of strategic alliances and relationship-building than has been previously
      described in the literature on community-level and health-promotion
      collaborations. This article utilizes qualitative data to illustrate the ways in
      which state-level partnerships for systems change both confirm and extend
      previous models. Findings indicate that state-level public health partnerships
      share many of the challenges and opportunities of locally-based and health
      promotion-oriented partnerships. Collaboration at the state level, however,
      involves more attention to organizational alliances, coordination of
      institutional change, and strategic responses to political changes. These
      partnerships depend on a combination of interpersonal skills, material resources,
      and organizational savvy to manage complex planning and implementation processes.
      Influencing policy development and organizational redesign in public health
      systems requires nuanced understanding of the opportunities provided by various
      kinds of organizational partners.

PMID- 15253522
TI  - Local health department partnerships with faith-based organizations.
AB  - Collaboration between public health and faith communities is encouraged by
      national and state policies. The study in this article examined the prevalence,
      characteristics, and effectiveness of partnerships between faith-based
      organizations and local health departments in Wisconsin. Data were collected from
      local health departments using a 2-stage, cross-sectional survey. A subset
      analysis of partnerships that included faith-based organizations was conducted
      using descriptive, bivariate, and 2-level logit regression methods, with
      partnerships nested in health departments. Twenty-four percent of local health
      department partnerships included faith-based organizations (n = 224). Community
      assessment was the most commonly reported partnership focus. Partnerships that
      included faith-based organizations were more likely to include many partners and
      have few partners contributing financially. Partnerships that include faith-based
      organizations are no more likely to be effective than those that do not.
      Predictors of local health department/faith-based organizations effectiveness
      included having a budget and longer time in existence. Local health departments
      engage faith-based organizations in partnership strategies when addressing issues
      that require broad community attention. Partnership effectiveness is enhanced by
      existence of a budget and sufficient time for development.

PMID- 15253523
TI  - Three Hundred Sixty Degree Feedback: program implementation in a local health
      department.
AB  - Three Hundred Sixty Degree Feedback systems, while popular in business, have been
      less commonly implemented in local public health agencies. At the same time, they
      are effective methods of improving employee morale, work performance,
      organizational culture, and attainment of desired organizational outcomes. These
      systems can be purchased "off-the-shelf," or custom applications can be developed
      for a better fit with unique organizational needs. We describe the City of
      Milwaukee Health Department's successful experience customizing and implementing
      a 360-degree feedback system in the context of its ongoing total quality
      improvement efforts.

PMID- 15253524
TI  - Making strategic decisions about service delivery.

PMID- 15253525
TI  - An acute toxic neuropathy caused by organo-phosphate poisoning in hens.
AB  - OBJECTIVE: Organophosphorus compounds can induce an acute toxic peripheral
      neuropathy. In hens, the acute peripheral neuropathy was induced by poisoning
      with organo-phosphorus compound (OPC)--tri-ortho-cresyl phosphate (TOCP).
      METHODS: In the course of an acute TOCP-induced toxic neuropathy in hens the
      activity of following enzymes was analysed: asparaginase, glutaminase, glutamat
      dehydrogenase, AMP and adenosine deaminases and 5'nucleotidase; ALT (SGPT), AST
      (SGOT) and proteins levels were estimated. RESULTS: A decrease in activity of all
      analysed enzymes was observed; the amount of proteins was increased. CONCLUSION:
      The biochemical changes display the slowing or stoppage in axonal transport of
      proteins. The disturbance of axoplasmic flow and the axonal demyelination may be
      considered as an attribute of peripheral neuropathy. (Tab. 1, Fig. 1, Ref. 32.).

PMID- 15253526
TI  - Treatment strategy of pineal tumors in consideration of their pathomorphology.
AB  - BACKGROUND: Tumors of the pineal gland are rare pathology. This paper reports on
      therapeutical considerations of histologically heterogeneous pineal tumors in a
      group of 15 patients and is presenting a special case of neuroaxial seeding.
      METHODS: Surgery and/or additional therapeutic procedures were performed in 13 of
      our 15 patients ("youngster" and "adults") in respect of pathomorphology. Details
      are reported concerning a 52-year-old man suffering from pineocytoma (WHO grade
      II), who underwent different kinds of therapy within 10 years follow-up. RESULTS:
      In the six "youngster" the histological assessment revealed two teratomas, one
      mixed pineocytoma/pineoblastoma, one astrocytoma and one epidermoid cyst. All
      neoplasms were treated surgically with good results. Additional radio
      /chemotherapy was used in a case of teratoma and pineocytoma/pineoblastoma. From
      five successfully surgically treated "adults" (germinoma, pineoblastoma,
      pineocytoma, two cystic formations) in two of them (germinoma, pineoblastoma)
      additional radiotherapy was needed, another two patients (cystic formations) were
      healed after stereotactic puncture. The patient with pineocytoma showed recurrent
      neuroaxial seeding within 10 years in spite of repeated radiotherapy, though his
      neurological status remained stable (Karnofsky performance score of 100).
      CONCLUSION: Precise histopathological assessment of pineal tumors is essential to
      guide optimal modern therapy modalities in order to assure a local tumor control.
      (Fig. 3, Ref. 18.).

PMID- 15253527
TI  - Esophageal dysfunction in a female patient with diabetes mellitus and achalasia.
AB  - BACKGROUND: Achalasia is an infrequent disorder of esophageal motility. Diabetes
      mellitus is an endocrine metabolic disease, the complication of which can afflict
      the motor activity of gastroenteral tract. The combination of these diseases in
      one patient is also very rare. In this study we introduce one patient suffering
      from this scarce coincidence of diseases. CASE HISTORY: A 54-year-old diabetic
      patient who lost weight of 26 kg in one month with repeated hypoglycaemic
      collapse states and regurgitation of poorly digested food and saliva with
      maintained appetite and thirst. The diagnosis of esophageal achalasia II was
      proved. A standard surgical performance was chosen, namely the laparoscopic
      myotomy. The extent of myotomy was verified by preoperative manometry.
      Approximately 1 month after the surgery, intermittent mild dysphagia especially
      after the consumption of solid food and some sorts of fruit appeared. The
      suspicion of stricture in the site of myotomy led us to the performance of
      endoscopic and radiologic examinations. The balloon calibration of cardia did not
      reveal any residual muscular fibres. The supplementation of a prokinetic drug of
      itoprid three times a day resulted in a significant improvement of difficulties.
      CONCLUSION: Despite the sufficient extent of surgical treatment in a patient
      suffering from these two diseases, the resulting effect was not fully
      satisfactory. It is apparent that despite the correctly indicated and performed
      operation in patients suffering from a metabolic disease, the complications of
      which afflict the motility of upper digestive tract, the ideal response to
      treatment cannot be expected. The supplemented prokinetic therapy is inevitable,
      and informing the patient on the expected result and particular residual
      disorders can save both the patient and surgeon from disappointment. (Fig. 3,
      Ref. 8.).

PMID- 15253528
TI  - Early results and experience with Furlow double opposing Z-plasty.
AB  - Since the establishment of the Cleft Centre in Bratislava efforts have been made
      to introduce new progressive operative techniques intended to improve both
      functional and aesthetical results of the procedures. As a consequence of these
      efforts the Langenbeck and Veau techniques used for ten years were in the 70-ties
      replaced with the Wardill-Kilner technique based on the "push-back" principle.
      The most recent trend in the palate repair is the Furlow double opposing Z-plasty
      used since 2002. The article is focused on the early results and experience with
      the Furlow palatoplasty. (Fig. 6, Ref. 18.).

PMID- 15253529
TI  - Sympathetic skin response: review of the method and its clinical use.
AB  - Sympathetic skin response (SSR) represents a potential generated in skin sweat
      glands; it originates by activation of the reflex arch with different kinds of
      stimuli. The potential of rapid habituation after repeated stimuli is formed by
      biphasic or triphasic slow wave activity with relatively stable latency and
      variable amplitude. In healthy subjects younger than 60 years of age the response
      is always present in all extremities. SSR is most frequently used in diagnosing
      the functional impairment of non-myelinated postganglionic sudomotor sympathetic
      fibers in peripheral neuropathies. In this study a more complex and informative
      view on the anatomical and physiological substrates of SSR, its character, normal
      values and technique are presented, focusing on problems in evaluation of the
      response and factors that have influence on it. Based on personal experience
      normative latency and amplitude values of SSR in a group of 20 healthy
      individuals (x +/- SD), upper extremities: 1.48 +/- 0.80 sec., 444 +/- 167
      microV, respectively; lower extremities: 2.06 +/- 0.93 sec., 203 +/- 87.4 microV,
      respectively) and recommendations for qualitative evaluation preference--the
      presence or absence of the response--over quantitative evaluation of latency and
      amplitude of the response in practical clinical use of the method are presented.
      (Tab. 1, Fig. 2, Ref. 148.).

PMID- 15253530
TI  - A sewage disposal failure as a cause of ascariasis and giardiasis epidemic in a
      family.
AB  - In monitoring the incidence of intestinal parasites in children and employees of
      a nursery the authors examined 31 children with 8 (25.81%) and 16 employees with
      3 (18.75%) positive results. The authors wanted to examine also the family
      members of 8 positive children and 3 positive employees but except from the
      cleaner's family, (Ascaris lumburicoides, Enterobius vermicularis and Entamoeba
      coli) nobody accepted the offer. All 8 members of a large family except for
      Patient 1 (a cleaner) and her grandson were without clinical and laboratory
      findings. They constitute 3 independent families who lived in 1st category flats.
      On August 31 there was an extensive sewage disposal failure in the ground floor
      flat of Family II and the flat was flooded by sewage. All family members worked
      solidarily on cleaning and also the members of Family IV who are friends of
      Family II. As shown by clinical symptoms of 'virosis', during the pre-patent
      period and after an outbreak within 73-78 days, laboratory findings of the family
      members demonstrated a severe family infection equal to a epidemic of intestinal
      parasitosis. Ascaris lumbricoides was diagnosed in 8 family members (61.54%) and
      Giardia intestinalis in 7 family members (53.85%) involved in cleaning.
      Enterobius vermicularis was found in 2 and Etamoeba coli in 1 family member. In
      monitored persons, in extreme hygienic conditions during the failure and later, a
      mass contraction arose on the basis of infection. The fact, that family epidemic
      arose subsequently, proved, in contrast to sporadic findings in children and
      adults, a 6.4 and 3.3 times higher incidence of Ascaris lumbricoides and a 5.6
      and 8.6 times higher incidence of Giardia intestinalis. The authors discus the
      reasons of incidence and also preventive measures in population. (Tab. 3, Ref.
      29.).

PMID- 15253531
TI  - Drug use--problem in pregnancy.
AB  - OBJECTIVE: The consumption of drugs during pregnancy considered as a specific
      medical problem. Drug consumption and drug compliance in pregnancy were analysed
      in our study. METHODS: Structured questionnaire and data from mothers were used
      as principal sources for analysis. Consumption of drugs and compliance with
      therapy were evaluated in 331 pregnant women, 60% city and 40% rural population,
      of Region Nitra, Slovakia, after their child birth. RESULTS: Drug's use was
      confirmed in 75% of pregnant women. The consumption was significantly higher in
      the first and second pregnancy when compared to the females by in their third or
      further pregnancies. Medical prescription was the reason of drug use in 89%
      pregnant women. The number of prescribed drugs similarly as the total consumption
      was higher in the first and second pregnancies. We noted medical prescribing drug
      compliance in 70% pregnant women. 16% of pregnant women used anagetic drugs, out
      of whom 57% on the basis of medical prescription. CONCLUSION: Adverse drug
      reactions (gastrointestinal problems and)headache were reported by 15% of
      pregnant women. In the observed group 6% of women gave birth premature infants
      (once gemini, once trimini). Two newborns overcomed sepsis. One baby suffered
      from cheilognatopalatoschisis and two newborns from vitium cordis congenitum. We
      do not suppose any correlation between child abnormalities and drug consumption
      during pregnacy. (Tab. 1, Ref. 9.).

PMID- 15253532
TI  - Interactive dynamic system of didactic means in medical studies.
AB  - Didactic means are an integral part of teaching also in the process of healthcare
      and doctoral education. They are applied not only in teaching of theoretical, but
      also in that of clinical subjects at medical faculties. The forms and levels of
      the use of didactic aids are subject to a dynamic process of transformation. They
      take place in form of conceptions, projects, realizations, results and effects. A
      part of them represent a domain of professionals, others are affected by
      basically non-professional teachers. The results and effects are influenced by
      students. The authors of this study present the didactic means used at the
      Faculty Medicine of Comenius University (FMCU) in Bratislava. (Tab. 1, Ref. 11.).

PMID- 15253533
TI  - Separation of Siamese twins in Bratislava.
AB  - At the pediatric surgical clinic in Bratislava, in the year 2000, we successfully
      carried out the separation of Siamese twins, which we classified as "ischiopagus
      tetrapus"+. The pelvic ring, the gastrointestinal tract and the urogenital system
      were all malformed. There was a common terminal ileum and only a short segment of
      the large intestine with a blind end. This was a case of non-developed anal
      segment and rectum. Each of the twins had two kidneys and two commonly shared
      urinary bladders. There were two uteruses, which were both bicornuate in nature
      with a fallopian tube arising from each of the horns as well as an ovary. The
      orifices of both urinary bladders and those of the two uteruses joined into a
      common urogenital sinus. The external ostia of this sinus represented a bizarre
      fissure with a single skin fold similar to the labium majus, located dorsally at
      the point of fusion of the pelvic structures. The act of separation was performed
      in two stages. Separation of the gastrointestinal tract was urgent due to the
      severe ileus caused by aplasia of the anus and the rectum. This first stage
      procedure was performed on the third day of admission (24.2.2000) after the
      babies had spent a month in other health institutions. The definitive separation
      was carried out a month after the first procedure (28.3.2000) following the
      optimal stabilization of the functions of the gastrointestinal tract. The
      uropoietic and genital systems were separated. A new pelvic ring and a pelvic
      floor were formed. The anterior abdominal wall was reconstructed and plastic
      correction of the skin in the gluteal and perineal regions was performed. The
      colostomies are functioning well and the twins pass well-formed stools. Lucia has
      long dry intervals between mictions. Andrea has shorter dry intervals. The girls
      have recently celebrated their third birthday. Their mental development is
      excellent; they speak Slovak and Hungarian languages. They have a well-developed
      locomotive apparatus, without any movement impairments. (Tab. 1, Fig. 16, Ref.
      10.)

PMID- 15253534
TI  - Antioxidant status of patients after on-pump and off-pump coronary artery bypass
      grafting.
AB  - BACKGROUND: It has been convincingly established that cardiopulmonary bypass
      routinely used in cardiac surgery induces an oxidative stress. The extensive
      production of reactive oxygen species occurring during cardiopulmonary bypass has
      a deleterious effect on the endogenous antioxidant defense pool. The recovery of
      antioxidant enzyme activities as well as other antioxidatively substances is one
      of the important tasks for the effective defense of patients in the postoperative
      period. AIM OF THE STUDY: Oxidative stress markers and the antioxidant status and
      the activities of some antioxidant enzymes were studied in patients during one
      week period after cardiac revascularization performed using cardiopulmonary
      bypass and the results were compared with patients operated by off-pump
      technique. PATIENTS AND METHODS: Thirty-nine patients undergoing elective
      surgical revascularization (coronary artery bypass grafting) were divided in two
      groups: twenty-two patients operated using cardiopulmonary bypass (group A) and a
      group B of seventeen patients undergoing pump-off surgery. Blood samples were
      drawn before operation and then in course of the first week after surgery. The
      following biochemical parameters were estimated: plasma levels of total
      antioxidant status (TAS) and of thiobarbituric acid reactive substances (TBARS)
      as well as erythrocyte activities of two antioxidant enzymes--superoxide
      dismutase (SOD) and glutathione peroxidase (GPx). RESULTS: There was a
      significantly decreased preoperative and also postoperative levels of TAS
      associated with a preoperatively increased level of TBARS in group A only. In
      both groups of patients (especially in group B), markedly decreased activity of
      SOD was observed. The increase of GPx activity--especially on the third
      postoperative day--was not significant. CONCLUSIONS: Regardless of the surgical
      technique, both groups of patients had a markedly decreased antioxidant capacity
      with a significantly increased production of lipid peroxides especially in
      patients operated with cardiopulmonary bypass. The decreased antioxidant status
      was connected with decreased erythrocyte activity of SOD. Therefore, we recommend
      the regular supply of antioxidant acting substances (antioxidant vitamins and
      coenzyme Q10) be included in their standard therapeutic strategy especially in
      the preoperative period. (Tab. 2, Fig. 4, Ref: 22.)

PMID- 15253535
TI  - On-pump cardiac surgery in a conscious patient using a thoracic epidural
      anesthesia--an ultra fast track method.
AB  - OBJECTIVE: To demonstrate the applicability and efficacy of spontaneous
      ventilation during cardiac surgery. METHODS: From March 1999 through December
      2002, 129 awake patients were operated on; 90 on-pump and 39 off-pump. A thoracic
      epidural space blockage was performed one hour prior to an incision being made at
      the Th 2-Th 4 level. Medial approach was used and the hanging drop method was
      routinely employed for epidural space detection. RESULTS: There were 82 male and
      47 female patients with a mean age of 64.5 years. Forty two cases were aortic
      valve replacement, 32 patients underwent on-pump coronary artery bypass grafting
      (CABG), 12 underwent mitral valve replacement, 27 patients were indicated for
      sternal wound reexploration, 12 for off-pump CABG, one for aortic valve
      replacement with aortic arch reconstruction and aortic valve replacement together
      with CABG was performed three times. There were ten conversions to general
      anesthesia and there was no death. Mean duration of the stay in the intensive
      care unit was 7.2 hours and in the hospital 5.1 days. We did not observe low
      cardiac output syndrome, stroke, renal insufficiency or pulmonary dysfunction in
      patients who sufficiently underwent thoracic epidural anesthesia. Less pain at
      assessments was demonstrated (Visual Analgetic Score=3.3). CONCLUSION: The recent
      interest in rapid recovery and early out-patient care of patients after cardiac
      surgery has prompted investigations into the use of neuraxial analgesia for these
      procedures. The above mentioned technique would be beneficial for patients with
      preoperative pulmonary dysfunction and may be particularly useful in endoscopic
      cardiac surgery. (Tab. 1, Fig. 2, Ref. 18.)

PMID- 15253536
TI  - Comparison of the exercise ECG and stress myocardial SPECT in detection of the
      significant coronary artery disease in the asymptomatic patients with diabetes
      mellitus type 2.
AB  - BACKGROUND: Diabetes mellitus is known to be a risk factor of the coronary heart
      disease even in the asymptomatic patients. Only a limited number of reports
      comparing the significance of different noninvasive stress tests in establishing
      the diagnosis of the advanced coronary lesions exists. OBJECTIVES: The aim of the
      study was to compare the significance of 12-lead exercise ECG and the myocardial
      SPECT in order to detect the significant coronary heart disease in asymptomatic
      type 2 diabetics. METHODS: 126 type 2 diabetic patients with negative history and
      no clinical or electrocardiographic signs of coronary heart disease were examined
      with the exercise ECG and the stress myocardial SPECT. The selective coronary
      angiography (SCG) was recommended to all patients with an abnormal SPECT or (and)
      a positive exercise ECG. The SCG was recommended to patients with equivocal
      results of the stress myocardial SPECT as well. RESULTS: 33 out of 126 examined
      patients (26.2%) had an abnormal, 33 equivocal and 60 normal stress myocardial
      SPECT. The exercise test could be evaluated in 99 examined patients (78%). 25
      diabetics had positive test (19.8%). The correlation between the results of 2
      tests was very good (p=0.0001). 38 patients had SCG, 24 with the abnormal SPECT,
      13 with equivocal and 1 with normal SPECT. Out of these 20 patients had positive,
      10 negative and 8 non-assessable exercise ECG. The relation between the presence
      of significant coronary stenosis (stenosis >70%) and the presence of abnormal
      stress myocardial SPECT was stronger (p=0.006) when compared with the positive
      exercise test (p=0.037). For the significant coronary stenosis the positive
      predictive value was 90% with the stress myocardial SPECT and 68% with the
      exercise ECG. CONCLUSION: The significance of the exercise ECG is lower
      predominantly due to high proportion of patients with non-assessable results. For
      the presence of significant coronary stenosis the positive predictive value of
      the stress myocardial SPECT is better than that of the exercise ECG. (Tab. 2,
      Ref: 25.)

PMID- 15253537
TI  - Morphological changes of small bowel graft in Wistar rats after preservation
      injury.
AB  - OBJECTIVE: In our study we decided to define the harvesting and preservation
      injury of the graft using Park's scheme for the quantification of morphological
      changes. METHODS:  ANIMALS: Male Wistar rats (n=25) weighting 322+/-18 g.
      Harvesting preservation technique: Proximal jejunum (5-7 cm) was flushed with 5
      ml of HTK solution and preserved for 0, 1, 6, 9 and 12 hours at 4 degrees C in
      the same solution. Biopsies for light microscopic evaluations were obtained after
      the preservation period. Park's scheme was used for the quantitative assessment
      of histological changes. t-test for two independent samples was used to evaluate
      statistical significance. RESULTS:  HISTOLOGY: The extent of the preservation
      injury in the samples obtained at 0 hours was of grade 0 and increased to 1.84
      after 12 hours of preservation time. At 0 hours of preservation a degree of 0
      (s=0: no changes) was observed, after 1 hour, a degree of 0.50 (s=0.47: slight
      changes, similar to 0 time), after 6 hours a degree of 1 (0.97, s=0.41: discrete
      subepitelial oedemas in villi apexes), after 9 hours a degree of 2 (1.74, s=0.64:
      extension of subeppitelial spaces in villi apexes), and after 12 hours a degree
      of 2 (1.83, s=0.64: more extension of subepitelial spaces) was observed, except
      for these findings, there were also changes of grade 3 (massive subepitelial
      edema and sequestration of the mucosa from lamina propria) in the 12-hour group.
      A statistically significant (p=0.05) difference was found between all groups
      except for 9 and 12-hour groups. CONCLUSIONS: HISTOLOGY revealed increasing
      preservation injury with a increasing duration of preservation and its dynamic.
      (Tab. 1, Fig. 2, Ref: 6.)

PMID- 15253538
TI  - The influence of hyperoxia on cough reflex intensity in guinea pigs treated with
      bleomycin.
AB  - Inhalation of high concentration of oxygen produces a lung injury in men and
      experimental animals. In our previous experiment we have found suppression of
      cough reflex in healthy guinea pigs after an exposure to 100% O2 for 60 hours.
      This study was designed to find the effect of hyperoxia on cough reflex in guinea
      pigs with lungs damaged by bleomycin. We used 48 animals (300-400 g) in two
      separated experiments. 32 of them were intratracheally injected with 1.5 mg
      bleomycin (Bleocin, Nippon Kayaku Co., Ltd., Tokyo, Japan) for induction of lung
      damage according to the method described by Parizada et al (20). 16 animals were
      given saline, only (control). Animals of experimental group were divided into two
      subgroups according to the lapse of time from bleomycin application. 13 days
      after bleomycin application animals of the 1st subgroup (16) were exposed to 100%
      O2 (8) or to room air (8) for 48 h. Similarly, 20 days after bleomycin
      application guinea pigs of the 2nd subgroup (16) were exposed to 100% O2 (8) or
      air (8), respectively. Cough was provoked in conscious animals placed in
      bodyplethysmograph box by inhalation of citric acid aerosol (0.3 mol/L) before,
      then 13 or 20 days after bleomycin application, and finally at the end of 48-h
      exposition to 100% O2 (air). The number of coughs was counted from airflow trace
      recorded by pneumotachograph. Cough was also induced by mechanical stimulation of
      laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized
      animals (Urethane, 1.1 g/kg, i.p.) just after the end of oxygen exposition and
      was evaluated from the interpleural pressure record. The results have shown a
      tendency to inhibition of citric acid cough reflex in animals 13 days treated
      with bleomycin and exposed to 100% O2, and significant decrease in citric acid
      induced cough in animals 20 days treated with bleomycin and exposed to 100% O2.
      Significant changes were present in cough intensity induced by mechanical
      stimulation of TBr region of the guinea pigs airway treated with bleomycin and
      exposed to oxygen, too. (Tab. 1, Fig. 3, Ref: 29.)

PMID- 15253539
TI  - Retrospective analysis of patients clinical manifestations before and after
      pheochromocytoma surgery.
AB  - MAIN PURPOSE: A retrospective analysis of presurgical clinical picture and blood
      pressures of 34 patients with histologically verified pheochromocytoma.
      Assessment of clinical state, blood pressure and prognosis in the course of
      patients control hospitalizations from 2001 to 2002. PATIENTS AND METHODS: The
      study was designed as a synoptic one, based on a retrospective analysis of 34
      patients records with histologically verified pheochromocytoma (26 women and 8
      men). Our assessments of clinical symptomatology, maximum paroxysmal hypertension
      values, average blood pressure values in patients with persistent arterial
      hypertension, arterial hypertension grade and circadian index were based on
      patients records. Patients epinephrectomies were followed during their control
      hospitalizations to assess their clinical state. Their blood pressures were
      evaluated by means of their circadian monitoring. RESULTS: From the 34 patients,
      21 were diagnosed with solitary pheochromocytomas. The circadian index
      persistence analysis prior to the surgery was associated with circadian blood
      pressure monitoring in 21 patients. It was lost in 57% of patients. During their
      control hospitalization as many as 82% of patients preserved their circadian
      blood pressure variability with a more than 10% decrease in the night time, 5
      patients did not preserve their circadian blood pressure variability. Seven from
      the original 34 patients died: Three of them died from their primary disease, one
      63-year old man died from shock following tumour extirpation. The death of other
      3 patients was not associated with their primary disease. CONCLUSION: Long
      lasting survival of patients with pheochromocytoma after surgical treatment-
      except for those with malignant disease--was demonstrated. Although our
      assessment of the resulting treatment effects was positive, a long-term follow-up
      is inevitable because of a difficult pathologic-anatomical verification of the
      malignant nature of the disease as well as of the risk of tumour relapse
      assessment. (Tab. 1, Fig. 5, Ref 36.)

PMID- 15253540
TI  - Echocardiographic evaluation of left ventricle postnatal growth in newborns and
      infants.
AB  - BACKGROUND: During intrauterine life is the volume stimulation of the left
      ventricle low and it's cardiac output in comparison to the right ventricle is
      about 50%. Before and also after birth the right ventricle is dominant.
      Postnatally low-resistance placenta is excluded from the systemic circuit,
      leading to an abrupt pressure elevation and to its further increase. AIM OF
      STUDY: The authors performed echocardiographic evaluation of healthy children
      from newborn age to 6 month of age. METHODS: Fifty randomly selected healthy
      mature infants were included in this study. Echocardiographic examination was
      performed at the age of 5 days, 1 month and 6 months respectively. Data obtained
      at the age of 5 days were compared to those at 1 month and 6 months. RESULTS: The
      authors confirmed a significant increase in the left ventricular volumes (LVESV,
      LVEDV, SV) developed early newborn in the period to 6 months of age. There was a
      significant increase in EF in the period age of 5 days to 1 month of age. Mean
      LVM on the 5th day after birth was 8.13+/-1.50 g. It increased to 11.39+/-2.33 g
      after 1 month and to 16.61+/-2.75 g after 6 months. They confirmed significant
      LVMVI decrease to 1.38+/-0.25 g/ml (6 months) from 1.56+/-0.33 (1 month). The
      authors found significant decrease in RWT values at the age of 6 months compared
      with the 5th day. CONCLUSION: Left ventricular parameters confirm postnatal left
      ventricle growth in healthy infants. The results are useful in interpretation of
      echocardiographic examinations in newborns and infants.

PMID- 15253541
TI  - Conditions responsible for small bowel resection.
AB  - The authors deal with the problems of surgery of small intestine. They analyze
      causes leading to small bowel resection, including small intestinal obstructions,
      tumors, diverticles, Crohn's disease and traumas of small intestine, in a group
      of patients operated at Ist Department of Surgery, University Hospital, Commenius
      University, Bratislava, during the last 30 years. Authors also discuss the
      problems of short bowel syndrome (SBS) as the consequence of an extensive small
      bowel resection, reporting the surgical approach to its therapy. (Tab. 1., Ref.
      5.)

PMID- 15253542
TI  - Vascular endothelial growth factor immobilized on platinum microcoils for the
      treatment of intracranial aneurysms: experimental rat model study.
AB  - Platinum microcoils coated with immobilized recombinant human vascular
      endothelial growth factor (rhVEGF) were prepared and the effectiveness for the
      embolization of aneurysms was investigated using a rat model. Platinum coils were
      prepared by successive deposition of cationic polyethyleneimine and anionic
      heparin, and VEGF was immobilized through affinity interaction with heparin.
      Unmodified, heparin-coated, or rhVEGF-immobilized platinum coil segments were
      inserted into the ligated external carotid arteries at the bifurcation of the
      common carotid artery (CCA) of adult female rats. The bifurcation segments of the
      CCA were harvested 2 weeks after the coil placement. rhVEGF-immobilized coils
      showed significantly greater endothelial formation at the aneurysm orifice and
      cell infiltration in the aneurysm body compared with the unmodified and heparin
      coated coils. The percentage of sac occlusion was significantly greater in the
      rhVEGF-immobilized group (77.53 +/- 27.58%) than in the heparin-coated group
      (44.81 +/- 38.30%) and unmodified group (34.99 +/- 28.15%). Scanning electron
      microscopy showed a tendency for more fibrotic and cellular collections on the
      coil surface and more tissue mass filling in the coil lumen in the rhVEGF
      immobilized group. Platinum microcoils coated with immobilized rhVEGF may be
      effective for the obliteration of aneurysms.

PMID- 15253543
TI  - Morphometry of the anterior third ventricle region as a guide for the
      transcallosal-interforniceal approach.
AB  - The transcallosal-interforniceal approach is the most appropriate approach to
      localize and totally remove space-occupying lesions around the anterior third
      ventricle region such as craniopharyngiomas and gliomas. This study examined the
      microsurgical anatomy of the normal anterior third ventricle region in 81 adult
      cadaver hemispheres. The central sulcus was identified and surface landmarks
      determined as the points 5 cm (P5) and 7 cm anterior to the central sulcus (P7).
      The distances between P5 and P7 and the upper margin of the interventricular
      foramen, which delineate the surgical corridor chosen to avoid disturbance of
      important neural structures, were 46.26-60.96 (54.09 +/- 3.35) mm and 48.00-62.00
      (54.94 +/- 3.09) mm, respectively. The distances between the upper margin of the
      hemisphere and the cingulate sulcus, especially important for avoiding damage to
      the cingulate gyrus and other mesiolimbic structures, were 13.54-30.00 (21.28 +/-
      3.89) mm and 12.22-29.52 (21.12 +/- 3.90) mm at the level of P5 and P7. The
      distances between the upper margin of the hemisphere and the callosal cistern
      containing the pericallosal artery were 28.34-40.50 (33.94 +/- 2.84) mm and 28.16
      40.26 (33.50 +/- 2.61) mm, respectively. Normative morphometric data of the
      structures involved in the surgical procedure are necessary for planning and
      performance of the transcallosal-interforniceal approaches. This study of a large
      series of specimens shows that these measurements have large individual
      variations.

PMID- 15253544
TI  - Remote cerebellar hemorrhage following supratentorial craniotomy--case report.
AB  - A 63-year-old man presented with sudden severe headache. Computed tomography (CT)
      demonstrated subarachnoid hemorrhage. Cerebral angiography demonstrated an
      aneurysm of the anterior communicating artery. Left frontotemporal craniotomy and
      neck clipping of the aneurysm via the pterional approach were performed. CT
      obtained 18 hours after surgery revealed cerebellar hemorrhage, and magnetic
      resonance (MR) imaging 17 days postoperatively demonstrated that the hemorrhage
      was located within the folia. Neurological examination after surgery revealed
      slight dysarthria after drainage of cerebrospinal fluid (CSF) but no other
      neurological deficits. Follow-up CT and MR imaging showed characteristic findings
      of postoperative cerebellar hemorrhage clearly different from those of
      hypertension. The cerebellar hemorrhage was probably secondary to overdrainage of
      CSF. He was discharged without deficits.

PMID- 15253545
TI  - Thalamic arteriovenous malformation with an unusual draining system--case report.
AB  - A 52-year-old man suddenly experienced headache and vomiting. Computed tomography
      demonstrated a small area of hemorrhage in the right cerebellar hemisphere.
      Angiography revealed a thalamic arteriovenous malformation (AVM) fed by the
      bilateral medial posterior choroidal arteries and left marginal tentorial artery,
      and drained into the confluence via the cerebellar veins without flow into the
      supratentorial venous system. The draining veins included two varices, one of
      which, in the right cerebellar hemisphere, was thought to be the source of
      bleeding. The AVM nidus was removed via the right occipital transtentorial
      approach. A portion of a drainer adhered to the surface of the great vein of
      Galen but without opening into the galenic system and all drainers from this
      thalamic AVM flowed into the infratentorial cerebellar venous system.

PMID- 15253546
TI  - Intravascular papillary endothelial hyperplasia of the central nervous system-
      four case reports.
AB  - Four rare cases of intracranial intravascular papillary endothelial hyperplasia
      (IPEH) manifesting as cranial nerve disturbances occurred in 16-, 18-, 24-, and
      28-year-old females. Magnetic resonance imaging showed all lesions as isointense
      with strong enhancement on T1-weighted images, and as hyperintense on T2-weighted
      images. All lesions were removed via craniotomies. Histological examination found
      vascular structures and papillary spaces lined with endothelial cells showing
      immunoreactivity for CD31. Complete removal was curative in two cases, whereas
      incomplete removal resulted in cure in one case and residual deficits in one
      case. Iatrogenic deficits should be avoided in IPEH treatment by surgery.
      Differentiation from neoplasm such as angiosarcoma depends on histological
      characteristics.

PMID- 15253547
TI  - Isolated recurrence of granulocytic sarcoma manifesting as extra- and
      intracranial masses--case report.
AB  - A 30-year-old female presented with a rare case of isolated recurrence of
      granulocytic sarcoma manifesting as extra- and intracranial masses 16 months
      after successful treatment of acute myeloblastic leukemia (M-2). She presented
      with a swelling located on her forehead that had appeared just after hitting her
      forehead, and never diminished in size. The mass was elastic hard and not freely
      mobile. Computed tomography and magnetic resonance imaging demonstrated enhanced
      masses in the right frontal extra- and intracranial region with no bone
      destruction. There was no evidence of relapse in the bone marrow. Needle
      aspiration biopsy of the subscalpal mass was performed. Fluorescence in situ
      hybridization revealed AML1/MTG8 fusion gene associated with t(8; 21). Two
      courses of systemic chemotherapy with high-dose cytarabine and total neural axis
      irradiation resulted in complete remission.

PMID- 15253548
TI  - Metastatic adenocarcinoma of the dura mimicking petroclival meningioma--case
      report.
AB  - A 27-year-old female presented with gait disturbance and left facial paresthesia.
      She had a history of breast and lung masses not yet identified. Magnetic
      resonance (MR) imaging revealed a tumor suggesting a petroclival meningioma. Her
      symptoms worsened rapidly. MR imaging showed enlargement of the tumor. Subtotal
      removal of the tumor was performed. Histological examination revealed metastatic
      adenocarcinoma. Examination of the other masses confirmed adenocarcinoma
      originating from lung carcinoma. Dural metastases can be difficult to
      preoperatively differentiate from meningioma clinically or radiographically. MR
      spectroscopy and laboratory examinations such as cytologic and serologic studies
      are valuable for differential diagnosis. The final diagnosis of the tumor depends
      on the histological findings. However, careful monitoring of the patient's course
      is very important to detect rapid growth of metastases.

PMID- 15253549
TI  - Rapid regrowth of intracranial clear cell meningioma after craniotomy and gamma
      knife radiosurgery--case report.
AB  - A 24-year-old woman underwent craniotomy for falx meningioma (5 cm in diameter)
      on October 24, 1995. The deepest part of the tumor was located in the anterior
      horn of the lateral ventricle, which was not resected. The histology was clear
      cell meningioma (CCM), aggressive in nature. The MIB-1 labeling index was high
      (11%). She underwent gamma knife (GK) radiosurgery for the residual tumor with an
      irradiation dose of 16 Gy at the tumor periphery on May 24, 1996. The
      postradiosurgical course was uneventful. The residual intraventricular tumor
      gradually decreased in size, but the peripheral portion gradually grew into the
      diencephalic region. The patient remained in good condition for 5 years until
      September 2001, when she exhibited memory disturbance and lethargy. Magnetic
      resonance imaging demonstrated a large tumor (4.5 cm in diameter) in the
      diencephalon, compressing the optic nerves and fornix. The calculated tumor
      doubling time was 120 days. A second craniotomy was performed on October 9, 2001.
      The tumor was totally resected through the anterior transcallosal approach. The
      histology and the MIB-1 labeling index of the tissue from the second operation
      did not differ markedly from those of the first operation. Neither tumor
      recurrence nor metastasis has been observed to date. GK radiosurgery contributed
      to control of the residual intraventricular tumor, but the peripheral portion of
      the tumor, which received a relatively low radiation dose (16 Gy), grew rapidly.
      This suggests that a marginal dose of 16 Gy may not be sufficient for control of
      CCM.

PMID- 15253550
TI  - Treatment of spontaneous intracranial hypotension secondary to C-2 meningeal cyst
      by surgical packing--case report.
AB  - A 41-year-old man presented with progressive worsening of postural headache.
      Computed tomography (CT) showed bilateral subdural hematomas without prior
      history of trauma. The diagnosis was spontaneous intracranial hypotension (SIH).
      Conservative treatment with oral steroids failed to prevent gradual deterioration
      of the patient's consciousness. CT myelography revealed massive cerebrospinal
      fluid (CSF) leakage between the C-1 and C-2 levels. The leak was repaired
      surgically via a laminectomy. A cyst, thought to be a meningeal cyst, was
      discovered adjacent to the right C-2 nerve root, and CSF was seen seeping out
      from around the cyst after a Valsalva maneuver. The presumed dural defect of the
      cyst was sealed by packing with muscle fragments and fibrin glue. The symptoms
      disappeared soon after surgery. He was discharged 1 month after surgery without
      deficits. Most SIH cases are benign and can be managed conservatively, or by the
      epidural blood patch method. Surgery is more invasive than the epidural blood
      patch method, but should be performed in patients with a high cervical lesion and
      massive CSF leakage.

PMID- 15253551
TI  - Neuroendoscopic basket dilation technique for the fenestration of the ventricular
      wall or intracranial cysts--technical note.
AB  - A basket dilation technique has been developed for fenestration of ventricular or
      cystic walls, using a basket type widely used in the urological field to collect
      renal or ureteric stones. This technique allows deep-seated structures to be
      visualized directly through the expanded basket during dilation and the thinnest
      part of ventricular wall to easily be pierced, cut, and dilated. Fine control can
      be exerted over expansion pressure through the hand piece directly connected to
      the basket tip. In addition, the basket can be rotated to cut the floating tissue
      that must be removed around the stoma. This basket dilation technique is safer
      than the balloon inflation technique currently used because it allows
      visualization of deep-seated structures that cannot be seen through the balloon,
      and should therefore prove useful in third ventriculostomy, plasty of the sylvian
      aqueduct, and fenestration of intracranial cystic lesions.

PMID- 15253552
TI  - Analysis of absorption spectra of RC from the bacteria Blastochlorii viridis in
      near IR region using high-order derivative spectroscopy.

PMID- 15253553
TI  - A comparative study of sulfonium reversible inhibitors of cholinesterases of
      various animals.

PMID- 15253554
TI  - The substantiation of the energy foundations of the theory of resistance of
      phototrophic prokaryotic and eucaryotic cells to abiotic environmental factors:
      problems of resistance of the chloroplast.

PMID- 15253555
TI  - Genetic lesions during progression of hereditary non-polypous colorectal cancer.

PMID- 15253556
TI  - On the question of the mechanisms triggering apoptosis and proliferation of
      hepatocytes in partial portal ischemia of various duration in rats.

PMID- 15253557
TI  - Contribution of lipoxygenase metabolism to the brassinosteroid signaling pathway.

PMID- 15253558
TI  - Prediction of chronic liver diseases on the basis of the N-acetyltransferase 2
      phenotype.

PMID- 15253559
TI  - Protein microchips in quantitative assays for tumor markers.

PMID- 15253561
TI  - Thermal stability of collagen II in cartilage.

PMID- 15253560
TI  - P50/YB-1, a major protein of cytoplasmic mRNPs, regulates its own synthesis.

PMID- 15253562
TI  - Elementorganic bisonium reversible inhibitors of different cholinesterases.

PMID- 15253563
TI  - Transgenic tobacco plants producing human interleukin-18.

PMID- 15253564
TI  - Construction of an artificial immunogen, a candidate DNA vaccine encoding
      multiple CTL epitopes of HIV-1.

PMID- 15253565
TI  - New titin isoforms in skeletal muscles of mammals.

PMID- 15253566
TI  - Laser correlation spectroscopy of macromolecular complexes in blood serum as an
      effective method of monitoring the progress of bronchial asthma in children.

PMID- 15253567
TI  - In vivo cytoplasmic localization of the p40 protein of the L1 transposable
      element of human genome.

PMID- 15253568
TI  - On the catalytic activity of autoantibodies in multiple sclerosis.

PMID- 15253569
TI  - Connection between ethics and policy in health care.

PMID- 15253570
TI  - Student nurse attitudes towards homeless clients: a challenge for education and
      practice.
AB  - The purpose of this research was to describe attitudes of nursing students (and
      paramedic officers) towards marginalized clients. Convenience quota sampling in a
      major health faculty was employed. Students participated on a voluntary basis. A
      58-item Likert scale, developed by the authors, assessed the student nurses'
      attitudes. In general, attitudes towards homeless clients were neutral; detailed
      analyses, however, revealed that student nurses would decline to care for
      homeless clients in various situations. Personal experience with homeless
      patients and positive attitudes of nurses significantly contributed to increased
      quality of care and equality of treatment for homeless clients. Certain student
      nurse behaviors warrant immediate attention to prevent marginalized patients from
      being exposed to unfair, inaccessible and biased nursing care. Based on our
      results, we recommend that further research attention be paid to the role of
      ethics education and faculty behaviors, as faculty members serve as role models
      for professionalization.

PMID- 15253571
TI  - Nurses' attitudes to euthanasia: a review of the literature.
AB  - This article provides an overview of the scarce international literature
      concerning nurses' attitudes to euthanasia. Studies show large differences with
      respect to the percentage of nurses who are (not) in favour of euthanasia.
      Characteristics such as age, religion and nursing specialty have a significant
      influence on a nurse's opinion. The arguments for euthanasia have to do with
      quality of life, respect for autonomy and dissatisfaction with the current
      situation. Arguments against euthanasia are the right to a good death, belief in
      the possibilities offered by palliative care, religious objections and the fear
      of abuse. Nurses mention the need for more palliative care training, their
      difficulties in taking a specific position, and their desire to express their
      ideas about euthanasia. There is a need to include nurses' voices in the end-of
      life discourse because they offer a contextual understanding of euthanasia and
      requests to die, which is borne out of real experience with people facing death.

PMID- 15253572
TI  - The influence of nurses' attitudes, subjective norms and perceived behavioral
      control on maintaining patients' privacy in a hospital setting.
AB  - The research reported in this article examined the influence of nurses'
      attitudes, subjective norms and perceived behavioral control on maintaining
      patients' privacy during hospitalization. The data were gathered from 109 nurses
      in six internal medicine wards at an Israeli hospital. The research was based on
      the theories of reasoned action and planned behavior. A positive and significant
      correlation was shown between nurses' attitude to promoting and maintaining
      patient privacy and their planned behavior, while perceived behavioral control
      was the best variable for predicting the nurses' behavior. Better educated nurses
      believed that they had fewer resources and anticipated more obstacles in acting
      to promote and maintain patient privacy. This research adds a new dimension to
      what is already known about nurses' attitudes to maintaining patients' privacy,
      nurses' planned behavior and their actual behavior. The practical implications of
      the findings are the identification of factors that influence the attitudes and
      behavior of nursing staff, which, in turn, will enable allocation of resources
      for solving difficulties and removing obstacles. The results will allow the
      formulation of educational programs to guide staff and also the application of
      policies based on both patient and nursing staff needs.

PMID- 15253573
TI  - Privacy and confidentiality issues in primary care: views of advanced practice
      nurses and their patients--an APRNet study [corrected].
AB  - Various aspects of the concepts of privacy and confidentiality are discussed in
      relation to health care information in primary health care settings. In addition,
      findings are presented from patient and nurse practitioner focus groups held to
      elicit concerns that these two groups have in relation to privacy and
      confidentiality in their respective primary care settings. The focus groups were
      held prior to the implementation of the Health Insurance Portability and
      Accessibility Act in the USA. Implications for advanced practice registered
      nurses in primary care practices are provided.

PMID- 15253574
TI  - Obtaining informed consent in an Egyptian research study.
AB  - This article explores the concept of internationally acceptable codes of ethics
      within the context of an Egyptian nurse's PhD studies. Theoretical work,
      including gaining ethical approval for the project, took place in the UK, while
      the data collection phase of the study was done in Egypt. This highlighted areas
      where the Arab Muslim interpretation of some ethical principles, especially
      around the issue of gaining informed consent, differed from that currently
      accepted in British research ethics. The authors argue that it may not be
      possible, or even desirable, to standardize codes of ethics globally in areas
      such as academic research. Ethical principles develop from a unique mix of
      culture and religion. It may be more important to develop cultural competence
      that includes the ability to understand and respect the way in which ethical
      principles are interpreted by various societies.

PMID- 15253575
TI  - Acknowledging dependence: a MacIntyrean perspective on relationships involving
      Alzheimer's disease.
AB  - As people living with Alzheimer's disease experience their lifetime of memories
      slowly slipping away, they become dependent on society's independent practical
      reasoners family, health care professionals and society. Many people grow
      accustomed to the cognitive decline and begin to view the person with dementia as
      less than a person. In Dependent rational animals, Alasdair MacIntyre emphasized
      a moral framework that encompasses two sets of virtues needed for human beings to
      flourish in society and to achieve genuine common goods--the virtues of
      independent practical reasoners and the virtues of acknowledged dependence.
      Virtues of acknowledged dependence are discussed ethically in terms of
      benevolence towards those who are disabled or dependent upon people who are
      strong and independent. The authors propose that using MacIntyre's perspective of
      the two sets of virtues is valuable in the care of persons with Alzheimer's
      disease. According to MacIntyre, independent reasoners who understand and
      practice these two sets of virtues will help those people in communities who are
      dependent and vulnerable, and, subsequently, human flourishing can occur.

PMID- 15253576
TI  - Recent equality legislation in the UK.

PMID- 15253577
TI  - ICNE workshop conference, Amsterdam 5 October 2003 responsibility and
      vulnerability: a global perspective.

PMID- 15253578
TI  - Nurse poaching.

PMID- 15253579
TI  - Country profile: Switzerland.

PMID- 15253580
TI  - Acupuncture for low back pain in pregnancy--a prospective, quasi-randomised,
      controlled study.
AB  - This study was undertaken to investigate the effects of acupuncture in low back
      and pelvic pain during pregnancy under real life conditions, as compared with
      patients undergoing conventional treatment alone. A total of 61 conventionally
      treated pregnant women were allocated randomly into two groups to be treated or
      not by acupuncture. Twenty-seven patients formed the study group and 34 the
      control group. They reported the severity of pain using a Numerical Rating Scale
      from 0 to 10, and their capacity to perform general activities, to work, and to
      walk. We also assessed the use of analgesic drugs. Women were followed up for
      eight weeks and interviewed five times, at two-week intervals. All women
      completed the study. In the study group the average pain during the study period
      showed a larger reduction (4.8 points) than the control group (-0.3 points) (P <
      0.0001). Average pain scores decreased by at least 50% over time in 21 (78%)
      patients in the acupuncture group and in five (15%) patients in the control group
      (P < 0.0001). Maximum pain and pain at the moment of interview were also less in
      the acupuncture group compared with the control group. The capacity to perform
      general activities, to work and to walk was improved significantly more in the
      study group than in the control group (P < 0.05). The use of paracetamol was
      lower in the acupuncture group (P < 0.01). These results indicate that
      acupuncture seems to alleviate low back and pelvic pain during pregnancy, as well
      as to increase the capacity for some physical activities and to diminish the need
      for drugs, which is a great advantage during this period.

PMID- 15253581
TI  - The development of the MYMOP pictorial version.
AB  - The MYMOP is a well accepted quality of life instrument that is particularly
      suitable for assessing the effect of complementary therapies; however, some
      groups of patients find it difficult to use. A pictorial version was developed
      using faces instead of the numerical rating scale--it is called MYMOP pictorial.
      This version appears to be more acceptable to patients but has not been formally
      validated.

PMID- 15253582
TI  - The use of acupuncture and attitudes to regulation among doctors in the UK--a
      survey.
AB  - OBJECTIVE: To assess the usage of acupuncture by members of British Medical
      Acupuncture Society (BMAS) in their daily work, in the course of a survey of
      attitudes to regulation of the acupuncture profession. METHODS: A brief
      questionnaire survey of all members was conducted in December 2002. RESULTS:
      After a single mailing, 1112 members responded (a response rate of 48%). Seventy
      five percent of these were general practitioners. The majority were in support of
      a regulatory process. Ninety percent of respondents indicated that they use
      acupuncture in their practice, giving an average of about eight treatments per
      week. Sixty-one percent of these treatments are given within the National Health
      Service (NHS) at no cost to the patient. CONCLUSION: It is estimated that BMAS
      members provide a total of about one million acupuncture treatments each year, of
      which well over half a million are given within the NHS.

PMID- 15253583
TI  - Education, training and continuing professional development in medical
      acupuncture--a contemporary overview.
AB  - Most medical and complementary medicine practitioners will have some awareness of
      the government-driven requirement to set and maintain explicit standards for
      education and professional development. For many doctors, revalidation has become
      a concern because they worry that it will raise the requirements for practice and
      increase bureaucratic documentation in support of the process. For those who have
      integrated complementary practices into their work within the National Health
      System, issues of registration and regulation add a further complication. The
      publication of the Department of Health consultation document on proposals for
      statutory regulation of herbal medicine and acupuncture in March 2004 raises
      issues of particular significance for medically qualified practitioners (such as
      'medical acupuncturists'), and other health professionals whose practice includes
      complementary skills. This paper focuses on the educational implications of these
      recent developments and offers an informed perspective that includes a reflection
      on how education and training (as initial training and as continuing professional
      development) can best meet the needs of acupuncture practitioners in this fast
      changing environment.

PMID- 15253584
TI  - Writing case reports--author guidelines for acupuncture in medicine.
AB  - Case reports are particularly valuable in specialist clinical areas such as
      acupuncture to report new adverse events and to suggest possible new hypotheses.
      They can also be used to report events that have been reported previously but are
      rare or serious, in order to illustrate their frequency. They may illuminate the
      wider side of clinical practice by describing personal experiences of one
      practitioner. Constraints to writing case reports include finding time, working
      in isolation, and not having enough experience at the task. This article
      reproduces and develops a set of guidelines that were previously published, in an
      attempt to help authors to write thorough but succinct reports in a structured
      manner. The format for case reports includes an abstract, description of the
      case, literature search, discussion and summary or conclusions. Recommendations
      are made for the material to be included in each section. The policy of
      Acupuncture in Medicine is to require patient consent before accepting a report
      for publication.

PMID- 15253585
TI  - An audit of acupuncture in general practice.
AB  - An audit was conducted to determine the effects of acupuncture treatment used in
      a dedicated clinic in primary care by a GP, starting shortly after first learning
      acupuncture. The outcome measure was MYMOP2 which was developed into the MYMOP
      pictorial during the course of the audit to improve patient compliance. Out of 62
      patients enrolled in the audit, 55 completed both the initial and follow-up
      questionnaires: they had a mean age of 56 years, and included 43 women. The
      overall mean improvement in symptom 1 was 2.0 (standard deviation 1.6) scale
      points, and the improvement was significant in 30 patients (55%). Twenty-eight
      patients reported significant improvement in activity (58% of those reporting
      this section), and 23 patients (48% of those reporting) obtained a significant
      improvement in wellbeing. Adverse events were minor, though one patient fainted
      and fell to the floor. Although the conclusions of this audit are limited by its
      small size, nevertheless the results were generally encouraging, and the authors
      recommend that acupuncture should be considered for use in primary care for a
      wide range of complaints.

PMID- 15253586
TI  - Acupuncture treatment of phantom limb pain and phantom limb sensation in
      amputees.
AB  - Three case histories are presented in which amputees with acute or chronic
      phantom limb pain and phantom limb sensation were treated with Western medical
      acupuncture, needling the asymptomatic intact limb. Two out of the three cases
      reported complete relief of their phantom limb pain and phantom limb sensation.
      Acupuncture was successful in treating phantom phenomena in two of these cases,
      but a larger cohort study would be needed to provide more evidence for the
      success rate of this treatment technique for this indication.

PMID- 15253587
TI  - Acupuncture in patients with valvular heart disease and prosthetic valves--an
      apology.

PMID- 15253588
TI  - Acupuncture for osteoarthritis of the knee.

PMID- 15253589
TI  - Tension pneumothorax related to acupuncture.

PMID- 15253590
TI  - Position statements: advocacy or futility?
AB  - This introduction lays the groundwork for this issue on a Collection of Oncology
      Nurses' Position Papers. Position papers developed by professional nursing
      organizations reflect a theoretical and research foundation. The position papers
      in this collection are relevant to oncology nurses in various practice settings
      and discuss how we can use them most effectively in our various roles as patient
      advocates.

PMID- 15253591
TI  - Promoting professional oncology nursing practice through position papers.
AB  - The position papers discussed in this article emphasize issues that relate to the
      clinical practice of oncology nursing and focus on promoting nursing roles,
      decreasing barriers to nursing practice, and address issues pertinent to nursing
      education and research. Position papers are not only helpful for advocating
      policy change with government and regulatory bodies, but nurses can use them to
      directly improve their work environments.

PMID- 15253592
TI  - Tools for the advancement of quality care.
AB  - Position statements promoting quality cancer care are invaluable tools for
      oncology nurses. This article reviews the various position papers that promote
      quality cancer care, rehabilitation of people with cancer, the patients' rights
      to quality cancer care, participation in clinical trials, and those issues
      involving quality cancer care in the Medicare program.

PMID- 15253593
TI  - Tobacco control policies of oncology nursing organizations.
AB  - Nurses, the largest group of health care professionals, and the policies of
      nursing organizations, have tremendous potential to promote health and tobacco
      control. Policies addressing tobacco use have been implemented by a variety of
      national and international nursing organizations. This article reviews existing
      tobacco control policies in oncology nursing organizations.

PMID- 15253594
TI  - Nursing roles in cancer prevention position statements.
AB  - Preventing cancer saves the labor of mending social, economic, cultural, and
      emotional upheaval engendered by a diagnosis of cancer. The four position
      statements discussed in this article provide a wealth of perspective regarding
      the professional organizations' views on cancer prevention and the important
      roles of nurses.

PMID- 15253595
TI  - Consensus statements, positions, standards, and guidelines for pain and care at
      the end of life.
AB  - Standards, guidelines, and position and consensus statements by themselves do not
      change practice or improve pain management and care at the end of life. However,
      if they are used effectively, they support best practices, provide a forum for
      discussion of current recommendations, and provide nurses with the latest science
      and information to advocate for effective pain and symptom management.

PMID- 15253596
TI  - Back pain: the Australian experience.

PMID- 15253597
TI  - Psychiatric comorbidity in general practice.

PMID- 15253598
TI  - Managing 'metabolic syndrome' and multiple risk factors.

PMID- 15253599
TI  - Back pain-clinical assessment.
AB  - BACKGROUND: Low back pain accounts for approximately 5% of all general practice
      consultations. Although the majority of patients will have somatic low back pain
      of musculoskeletal origin, vigilance in excluding 'red flag' conditions is
      paramount. The identification of 'yellow flags', ie. psychosocial stress factors,
      becomes important in patients not making a rapid recovery, and these factors need
      to be identified and rectified early, lest they lead to chronic pain and
      disability. OBJECTIVE: This article presents a simple examination of the lower
      back designed with general practice in mind. It is based on the 'look, move,
      feel' paradigm of clinical orthopaedic examination. DISCUSSION: A thorough and
      conscientious physical examination is not time consuming. It reassures the
      patient that the practitioner is interested and concerned about their problem. In
      acute low back pain, this is the springboard to a simple effective management
      program and improved outcomes. It also confirms the site of pain, and is
      important in monitoring disability. However, there are no clinical signs, either
      singly or in multiples, which allow a valid anatomico-pathological diagnosis to
      be made.

PMID- 15253600
TI  - Acute low back pain: assessment and management.
AB  - BACKGROUND: Back pain is a common presenting problem in Australian general
      practice. Serious causes, however, are rare. Tumours, infections and fractures
      account for less than 1% of cases and can usually can be recognised or excluded
      by taking a careful history. Patients should expect a good outcome. OBJECTIVE:
      This article summarises the management of acute low back pain and sets out the
      key points in history taking including alerting factors for serious disorders,
      and psychosocial factors that enable a rational management plan. DISCUSSION: A
      specific cause of pain need not be established for appropriate management to be
      instituted, with the active engagement of the patient as partner. Although no
      pattern of pain is diagnostic, a sudden onset of unremitting pain should be
      regarded as a 'red flag' to a serious underlying disorder. In accordance with
      evidence based principles, clinicians need to take into account previous
      experience, personal preferences, and cultural factors when recommending therapy
      for individual patients.

PMID- 15253601
TI  - Lumbar radicular pain.
AB  - BACKGROUND: Radicular pain is caused by irritation of the sensory root or dorsal
      root ganglion of a spinal nerve. The irritation causes ectopic nerve impulses
      perceived as pain in the distribution of the axon. The pathophysiology is more
      than just mass effect: it is a combination of compression sensitising the nerve
      root to mechanical stimulation, stretching, and a chemically mediated noncellular
      inflammatory reaction. OBJECTIVE: This article discusses the clinical features,
      assessment and management of lumbar radicular pain (LRP). DISCUSSION: Lumbar
      radicular pain is sharp, shooting or lancinating, and is typically felt as a
      narrow band of pain down the length of the leg, both superficially and deep. It
      may be associated with radiculopathy (objective sensory and/or motor dysfunction
      as a result of conduction block) and may coexist with spinal or somatic referred
      pain. In more than 50% of cases, LRP settles with simple analgesics. Significant
      and lasting pain relief can be achieved with transforaminal epidural steroid
      injection. Surgery is indicated for those patients with progressive neurological
      deficits or severe LRP refractory to conservative measures.

PMID- 15253602
TI  - Diagnostic imaging for back pain.
AB  - BACKGROUND: X-rays and computerised tomography (CT) scans for back pain are often
      ordered to exclude pathology, to make a positive diagnosis and/or as a response
      to patient expectations. OBJECTIVE: This article reviews the evidence about the
      accuracy of diagnostic imaging to allow rational ordering without compromising
      patient satisfaction. DISCUSSION: X-rays make no difference to outcomes for back
      pain and related disability. For the exclusion of serious causes of back pain,
      the accuracy of X-rays and CT scans is limited. Most positive findings on
      radiological investigations, particularly degenerative findings, have little or
      no association with back pain. A history that includes the key features of
      serious causes will detect all patients requiring imaging. Care is required in
      explaining results of radiological investigations to patients to reassure about
      the absence of serious causes and to put incidental findings into perspective.

PMID- 15253603
TI  - Interventions in chronic low back pain.
AB  - BACKGROUND: Chronic low back pain presents a major challenge for general
      practitioners and is a significant drain on community resources. Patients often
      feel frustrated by modern medicine's apparent failure to validate their symptoms
      with a specific diagnosis and management plan. OBJECTIVE: This article presents
      an evidence based guide to current interventions, including an algorithm for the
      interventional diagnostic workup of low back pain that has persisted beyond 3
      months. DISCUSSION: Modern imaging techniques rarely determine the cause of pain.
      The GP must look for 'red flag' clues in the history. Management of low back pain
      includes NSAIDs, simple injections of plain local anaesthetic without adrenalin
      or cortisone, referral to a masseuse, cortisone, physiotherapist and/or a
      musculoskeletal pain physician. Specific management includes medial branch and
      sacroiliac joint blocks, and radiofrequency neurotomy. Patients with long term
      pain may be referred to a psychologist for cognitive behavioural therapy.

PMID- 15253604
TI  - Back pain rehabilitation.
AB  - BACKGROUND: Back pain is a universal problem that becomes persistent in 5-10% of
      patients following an acute episode. This makes it one of the most costly areas
      of health care in Australia. OBJECTIVE: This article outlines the paradigm that
      general practitioners should adopt to assist the patient to live with their pain
      experience. DISCUSSION: The development of persistent back pain is not a static
      process but one that is heavily influenced by the context in which it occurs.
      Patient characteristics, health care providers and the health system environment
      contribute and interact to promote the development of persistent pain. Health
      care providers involved in managing persistent pain should remain confidant,
      positive and reassuring. They should encourage activity, discourage fear
      avoidance behaviour, and consider rehabilitation early before illness beliefs
      become entrenched. Multidisciplinary rehabilitation, when used early, aims to
      improve function and assist in the return to work process; when used late, it
      aims to prevent worsening disability and increased coping for patients.

PMID- 15253605
TI  - Back pain and opioid seeking behaviour.
AB  - BACKGROUND: Back pain is a common presentation associated with opioid seeking
      behaviour. OBJECTIVE: This case study provides general practitioners with a
      practical approach to seeing patients with chronic pain whom they suspect of
      opioid dependence and describes a framework for managing chronic pain and
      dependence within the general practice setting. DISCUSSION: Back pain, with or
      without opioid dependence, is commonly encountered in general practice. General
      practitioners frequently find themselves caught between the desire to treat and
      relieve symptoms, and not wanting to cause or exacerbate dependence. Clear
      guidelines and access to support are often lacking.

PMID- 15253606
TI  - Patient education. Low back pain.
AB  - It is not always clear what causes acute back pain. It may result from injuries
      to muscles, ligaments, bones, joints and discs in the back or to injury to a
      combination of these structures. Increased muscle tension, for whatever reason,
      can increase pain. It is not usually possible to make a precise diagnosis, but in
      most cases the pain settles in few days or weeks. If pain persists it is
      important to follow up with your doctor.

PMID- 15253607
TI  - Practice tip. Undertaking a literature search using PubMed.

PMID- 15253608
TI  - Unilateral red eye. Eye series--16.

PMID- 15253609
TI  - Teaching medical students - what's in it for teachers?
AB  - The term 'doctor' comes from the Latin 'docere' meaning 'to teach'. Although few
      general practitioners have formal teaching skills or qualifications, we are all
      involved in teaching patients every day. The importance of our role as educators
      has been recognised for a long time, with the first statements of the Hippocratic
      Oath dealing with respect for our teachers and our duty to pass our knowledge on
      to others.

PMID- 15253610
TI  - How to plan, deliver and evaluate a training session.
AB  - The long term aim of general practice teaching is to train competent general
      practitioners to provide high quality care to patients in any setting. The Royal
      Australian College of General Practitioners' (RACGP) curriculum sets educational
      outcomes for postgraduate general practice training programs throughout
      Australia. Registrars have input to this process by reflecting on their learning
      needs and developing learning plans. This article discusses the teaching of
      practical procedures in general practice and describes the planning, delivery and
      evaluation of an educational session about the management of shoulder conditions
      for general practice registrars.

PMID- 15253611
TI  - A pain in the back case.
AB  - I This article discusses a Supreme Court case involving a patient who was
      referred to a chiropractor for treatment of neck pain. The case highlights some
      important issues, including the: importance of good medical record keeping, duty
      to read patient documentation, including previous medical records, duty to
      perform a physical examination, and duty to consider if a referral is appropriate

PMID- 15253612
TI  - Marriage: is it good for you?

PMID- 15253613
TI  - Postcard from Kirakira.

PMID- 15253614
TI  - Primary Care Alliance for Clinical Trials (PACT): building a network to
      facilitate quality randomised trials in primary care.

PMID- 15253615
TI  - Enhancing the population health capacity of general practice: an innovative
      training model for general practice registrars.

PMID- 15253616
TI  - Which patients are prescribed COX-2 inhibitors rather than nonspecific anti
      inflammatory drugs?

PMID- 15253617
TI  - Suboptimal anticoagulant management in patients after hospital initiation of
      warfarin.

PMID- 15253618
TI  - General practitioner multidisciplinary skills for enhanced primary care.

PMID- 15253619
TI  - Microwave-assisted sample treatment in a fully automated flow-based instrument:
      oxidation of reduced technetium species in the analysis of total technetium-99 in
      caustic aged nuclear waste samples.
AB  - An automated flow-based instrument for microwave-assisted treatment of liquid
      samples has been developed and characterized. The instrument utilizes a flow
      through reaction vessel design that facilitates the addition of multiple reagents
      during sample treatment and removal of the gaseous reaction products and enables
      quantitative removal of liquids from the reaction vessel for carryover-free
      operations. Matrix modification and speciation control chemistries that are
      required for the radiochemical determination of total (99)Tc in caustic aged
      nuclear waste samples have been investigated. A rapid and quantitative oxidation
      procedure using peroxydisulfate in acidic solution was developed to convert
      reduced technetium species to pertechnetate in samples with high content of
      reducing organics. The effectiveness of the automated sample treatment procedures
      has been validated in the radiochemical analysis of total (99)Tc in caustic aged
      nuclear waste matrixes from the Hanford site.

PMID- 15253620
TI  - Evaluation and optimization of an on-line admicelle-based extraction-liquid
      chromatography approach for the analysis of ionic organic compounds.
AB  - Admicelles-based solid-phase extraction (SPE) was on-line coupled with liquid
      chromatography/electrospray ionization/ion trap mass spectrometry, and it was
      proposed for the extraction of ionic organic compounds based on the formation of
      surfactant-analyte ion pairs. The approach was illustrated by studying the
      preconcentration of quaternary ammonium herbicides (quats) on sodium dodecyl
      sulfate (SDS) admicelles produced on alumina. Optimization of the parameters
      affecting SPE were studied on the basis that admicelles are dynamic entities in
      equilibrium with the aqueous phase. Some general guidelines could be established
      for method development from the results obtained. Factors influencing on-line
      operation were elucidated. On-line regeneration of the sorbent in each run was
      easily achieved by disruption of SDS admicelles with methanol and posterior
      coating of the alumina with SDS. The recovery of quats from drinking water
      samples were found quantitative for paraquat, diquat, and difenzoquat and above
      to 70% for chlormequat and mepiquat. Concentration factors of about 250, using
      sample volumes of 50 mL, were achieved. The detection limits ranged from 10 to 30
      ng/L. The approach developed permits compliance with the directives of the
      European Community for drinking waters (100 ng/L) and goes deeply into the basis
      of solid-phase extractions that use surfactant-coated mineral oxide as sorbents.

PMID- 15253622
TI  - Visible and near-infrared spectroscopy as a technique for screening the inorganic
      arsenic content in the red crayfish (procambarus clarkii Girard).
AB  - The potential of near-infrared spectroscopy (NIRS) for screening the inorganic
      arsenic (i-As) content in the red crayfish (Procambarus clarkii Girard 1852) was
      assessed. Sixty-two samples belonging to this species were freeze-dried and
      scanned by NIRS. The i-As contents of the samples were obtained by acid digestion
      solvent extraction followed by hydride generation atomic absorption spectrometry
      and were regressed against different spectral transformations by modified partial
      least-squares (MPLS) regression. Second derivative transformation equations of
      the raw optical data, previously standardized by applying standard normal variate
      and de-trending algorithms, resulted in a coefficient of determination in the
      cross-validation (1-VR) of 0.84, indicative of equations of good quantitative
      information. The standard error of cross-validation to standard deviation ratio,
      shown by the second derivative equation, was similar to those obtained for other
      trace metal calibrations reported in NIRS reflectance. Spectral information
      related to chromophores and lipids of the red crayfish tissues, and also the
      plant matter contained in their stomachs, were the main organic components used
      by MPLS for modeling the selected prediction equation. This pioneering use of
      NIRS to predict the i-As content in red crayfish represents an important savings
      in time and cost of analysis.

PMID- 15253621
TI  - Shielded stationary phases based on porous polymer monoliths for the capillary
      electrochromatography of highly basic biomolecules.
AB  - A novel stationary phase for capillary electrochromatography has been prepared
      via photoinitiated grafting of two layers of polymer chains onto the pore surface
      of a porous polymer monolith. To achieve the desired retention, the original
      monolith with optimized porous properties was grafted with an "interior" layer
      consisting of the ionizable monomer, 2-acrylamido-2-methyl-1-propanesulfonic
      acid, followed by a "covering" layer of hydrophobic polymer chains. This
      technique affords monolithic CEC columns that facilitate electroosmotic flow
      (EOF) while preventing ionized analytes from interacting with the charged surface
      functionalities. Grafting of the second layer does not adversely affect the EOF.
      Grafting times of 30 and 60 s for AMPS and butyl acrylate, respectively, enabled
      the preparation of a monolith with full shielding of the analytes from the
      ionizable functionalities and excellent chromatographic performance. This
      approach allows for the first time the independent optimization of both
      electroosmotic flow and retention properties in CEC columns. The efficient
      isocratic separations of mixtures of peptides, including some that are highly
      basic and would be affected by unshielded charges, were routinely achieved in 40
      90 s using a simple MS compatible mobile phase consisting of 20 mmol/L ammonium
      acetate in a 1:1 water-acetonitrile mixture.

PMID- 15253623
TI  - Control of magnetophoretic mobility by susceptibility-modified solutions as
      evaluated by cell tracking velocimetry and continuous magnetic sorting.
AB  - With the analytical expression for the magnetophoretic mobility of an ideal,
      linearly polarizable sphere undergoing creeping motion in viscous medium, we have
      shown that both attractive and repulsive motions are possible in the magnetic
      field. We have validated theoretical predictions using magnetic monodisperse
      microspheres of 5.2-microm diameter and nonmagnetic polystyrene microspheres of
      6.99-microm diameter suspended in solutions of paramagnetic ions. The microsphere
      magnetophoretic mobility was measured using a modified particle tracking
      velocimetry system, developed in-house and called a cell tracking velocimeter.
      The product of measured mobility and viscosity agrees well with the theoretical
      prediction, differing only by approximately 11%. Further, a 26% increase in
      resolution between magnetic and nonmagnetic particle distributions was evaluated
      when paramagnetic ion carrier was used instead of water. Continuous particle
      sorting based on differences in magnetophoretic mobility was performed with
      another device developed by us, the quadrupole magnetic flow sorter (QMS). In the
      QMS, the introduction of paramagnetic ions into the carrier was effective in
      suppressing nonspecific crossover (i.e., the transport of low-mobility particles
      into the magnetic particle fraction) in particles and in biologically relevant
      red blood cells and thus showed promise as a means of increasing the purity of
      the magnetic separation.

PMID- 15253624
TI  - Prediction of low-energy collision-induced dissociation spectra of peptides.
AB  - A kinetic model, based on the "mobile proton" model of peptide fragmentation, was
      developed to quantitatively simulate the low-energy collision-induced
      dissociation (CID) spectra of peptides dissociated in a quadrupole ion trap mass
      spectrometer. The model includes most fragmentation pathways described in the
      literature, plus some additional pathways based on the author's observations. The
      model was trained by optimizing parameters within the model for predictions of
      CID spectra of known peptides. A best set of parameters was optimized to obtain
      best match between the simulated spectra and the experimental spectra in a
      training data set. The performance of the mathematical model and the associated
      optimized parameter set used in the CID spectra simulation was evaluated by
      generating predictions for a large number of known peptides, which were not
      included in the training data set. It was shown that the model is able to predict
      peptide CID spectra with reasonable accuracy in fragment ion intensities for both
      singly and doubly charged peptide parent ions up to 2000 u in mass. The optimized
      parameter set was evaluated to gain insight into the collision-induced peptide
      fragmentation process.

PMID- 15253625
TI  - A method for connecting solution-phase enzyme activity assays with immobilized
      format analysis by mass spectrometry.
AB  - This paper reports an enzyme activity assay that combines the assets of both
      homogeneous and solid-phase formats. In this method, enzyme reactions are carried
      out in solution using substrates that are tagged with an immobilization reagent
      that allows the substrates to be selectively immobilized to self-assembled
      monolayers (SAMs), for direct analysis by matrix assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). As a model enzyme
      reaction, this work examined the transfer of a methyl group from S-adenosyl-l
      methionine (AdoMet) to an arginine side chain of a peptide substrate by the
      enzyme protein arginine methyltransferase 1 (RMT1). A cysteine-terminated peptide
      substrate was methylated by RMT1 in solution and then applied to a maleimide
      presenting SAM to give selective immobilization of the peptide. Time-dependent
      analysis of methylation using MALDI-TOFMS clearly showed that both the presence
      and relative amount of the two reaction products-the mono- and dimethylated
      peptides-can be conveniently evaluated. This assay strategy is rapid, takes
      advantage of solution-phase assay conditions, avoids the use of labels and
      complicated purification steps, and is applicable to multianalyte analyses.

PMID- 15253626
TI  - Atmospheric pressure MALDI-fourier transform mass spectrometry.
AB  - The coupling of atmospheric pressure matrix-assisted laser desorption/ionization
      (AP MALDI) with Fourier transform mass spectrometry (FTMS) is described, and its
      significance for the high-resolution analysis of complex peptide mixtures is
      demonstrated. High kinetic energy and extensive metastable decay characteristic
      of ions generated by vacuum MALDI have been known to constitute a possible
      obstacle to high-resolution analysis by FTMS. Since the initial coupling of laser
      desorption techniques with FTMS was realized two decades ago, several different
      solutions have been proposed to control the energy of the ions and fulfill the
      promise of high sensitivity and high resolution offered by this analytical
      method. Initial results obtained on quadrupole time-of-flight and ion trap
      analyzers have shown that ions generated by MALDI at atmospheric pressure are
      intrinsically less energetic than those provided by vacuum MALDI. Our report
      indicates that this characteristic is particularly beneficial for FTMS
      applications in which a sharp reduction of metastable decay can make larger ion
      currents available for detection and possible tandem experiments. In our hands,
      AP MALDI-FTMS has enabled the analysis of complex peptide mixtures with
      resolution and accuracy comparable to those obtained by analogous electrospray
      ionization-FTMS experiments, with no evidence of either metastable decomposition
      or significant formation of matrix adducts. Analysis of a trypsin digest of
      bovine serum albumin provided signal-to-noise ratios and limits of detection
      similar to those obtained by ion trap analyzers, but with unmatched resolution
      and accuracy. AP MALDI has been shown to provide stable precursor ions in amounts
      that allowed for informative tandem experiments. Finally, the potential of AP
      MALDI-FTMS for the high-resolution screening of complex mixtures was demonstrated
      by the analysis of isobaric peptides differing in mass by less than 0.04 Da.

PMID- 15253627
TI  - Selective isolation at the femtomole level of phosphopeptides from proteolytic
      digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns.
AB  - Selective detection of phosphopeptides from proteolytic digests is a challenging
      and highly relevant task in many proteomics applications. Often phosphopeptides
      are present in small amounts and need selective isolation or enrichment before
      identification. Here we report a novel automated method for the enrichment of
      phosphopeptides from complex mixtures. The method employs a two-dimensional
      column setup, with titanium oxide-based solid-phase material (Titansphere) as the
      first dimension and reversed-phase material as the second dimension.
      Phosphopeptides are separated from nonphosphorylated peptides by trapping them
      under acidic conditions on a TiO(2) precolumn. Nonphosphorylated peptides break
      through and are trapped on a reversed-phase precolumn after which they are
      analyzed by nanoflow LC-ESI-MS/MS. Subsequently, phosphopeptides are desorbed
      from the TiO(2) column under alkaline conditions, reconcentrated onto the
      reversed-phase precolumn, and analyzed by nanoflow LC-ESI-MS/MS. The selectivity
      and practicality of using TiO(2) precolumns for trapping phosphopeptides are
      demonstrated via the analysis of a model peptide RKISASEF, in a 1:1 mixture of a
      non- and a monophosphorylated form. A sample of 125 fmol of the phosphorylated
      peptide could easily be isolated from the nonphosphorylated peptide with a
      recovery above 90%. In addition, proteolytic digests of three different
      autophosphorylation forms of the 153-kDa homodimeric cGMP-dependent protein
      kinase are analyzed. From proteolytic digests of the fully autophosphorylated
      protein at least eight phosphorylation sites are identified, including two
      previously uncharacterized sites, namely, Ser-26 and Ser-44. Ser-26 is
      characterized as a minor phosphorylation site in purified PKG samples, while Ser
      44 is identified as a novel in vitro autophosphorylation target. These results
      clearly show that TiO(2) has strong affinity for phosphorylated peptides, and
      thus, we conclude that this material has a high potential in the field of
      phosphoproteomics.

PMID- 15253628
TI  - Buffer loading for counteracting metal salt-induced signal suppression in
      electrospray ionization.
AB  - The decrease in the sensitivity of electrospray ionization mass spectrometry
      caused by the presence of metal salts, such as sodium chloride, in the sample
      matrix is well known and is particularly problematic for biological samples. We
      report here that addition of high levels of ammonium acetate can improve analyte
      signal in aqueous electrospray solutions and counteracts the signal suppression
      caused by sodium chloride. A approximately 3-fold improvement in S/N is obtained
      by adding 8 M ammonium acetate to aqueous solutions of cytochrome c without added
      sodium chloride. No organic solvents or acids are added into the electrospray
      solutions. The signal-to-noise ratios of cytochrome c and ubiquitin (10(-)(5) M)
      ions formed from aqueous solutions containing 2.0 x 10(-)(2) M sodium chloride
      are improved by factors of approximately 7 and 11, respectively, by adding 7 M
      ammonium acetate to the solution. We propose that this effect is a result of the
      precipitation of Na(+) and Cl(-) from solution within the evaporating
      electrospray droplets prior to the formation of gas-phase protein ions. This
      method is potentially useful for improving the abundance of protein ions formed
      from solutions in which the molecules have a nativelike conformation and is
      particularly advantageous for such solutions that have high levels of sodium.

PMID- 15253629
TI  - Development of a chemical ionization ion trap mass spectrometric method for trace
      level determination of molecular halogens.
AB  - An ion trap mass spectrometric technique using negative ion chemical ionization
      has been developed for the quantitative determination of the molecular halogen
      species Br(2), Cl(2), and BrCl. The technique utilizes NO(2)(-) as a chemical
      ionization reagent in an electron-transfer reaction to form the corresponding
      molecular anions of the halogen species, lending excellent selectivity to the
      measurement. Reaction rate experiments performed in the ion trap yield a rate
      constant for Br(2) + NO(2)(-) --> Br(2)(-) + NO(2) of (1.4 +/- 0.6) x 10(-)(9)
      cm(3) molecule(-)(1) s(-)(1), determined relative to published data for Cl(2) +
      NO(2)(-) --> Cl(2)(-) + NO(2). This paper describes a mass spectrometer pinhole
      inlet design and cryogenic preconcentration system for detection of the molecular
      halogens at atmospherically relevant concentrations. Linear calibration curves
      were obtained for Cl(2) and Br(2) over 3 orders of magnitude and indicate limits
      of detection of 50 and 8 pmol for 3.8- and 5.1-L samples, respectively,
      corresponding to 220 and 50 parts per trillion (mole/mole). Quantitation is based
      on the total signal at m/z values of 70, 72, and 74 for Cl(2) and 158, 160, and
      162 for Br(2). The effects of water vapor on the cryogenic preconcentration step
      are quantitatively assessed.

PMID- 15253630
TI  - Divinyl sulfone as a postdigestion modifier for enhancing the a(1) Ion in MS/MS
      and postsource decay: potential applications in proteomics.
AB  - Divinyl sulfone reacts at pH 8-9 with the alpha-amino groups of N-terminal
      residues, proline, the epsilon-amino groups of lysine, and the histidine side
      chains of peptides. This reaction leads to great enhancement of the abundance of
      the normally weak or missing "a(1)" fragment ion in MS/MS analysis defining the N
      terminal residue of a peptide in a digest. This provides "one-step Edman-like"
      information that, together with a fairly accurately determined mass, often
      enables one to correctly identify a protein or family of proteins. The
      applicability of this procedure in proteomics was demonstrated with several
      peptides and tryptic digests of protein mixtures by LC-MS/MS experiments using a
      QTOF and MALDI-PSD analyses. Advantages of this approach are its simple
      chemistry, retention of charge multiplicity, and possibly, shortening of database
      search time. Used with other MS/MS data, it provides higher confidence in the
      scores and identification of a protein found in peptide mass fingerprinting.
      Moreover, this approach has an advantage in "de novo" sequencing due to its
      ability to decipher the first amino acid of a peptide whose information is
      normally unavailable in MS/MS spectra.

PMID- 15253632
TI  - Laser desorption/ionization mass spectrometry of diesel particulate matter with
      charge-transfer complexes.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are often associated with complex
      matrixes such as exhaust diesel particulate matter (DPM), which complicates their
      study. In that case, laser desorption/ionization mass spectrometry is one of the
      techniques which ensures their direct analysis in the solid state. We demonstrate
      in this paper that the use of charge-transfer pi-complexing agents allows us to
      selectively detect by Fourier transform ion cyclotron resonance mass spectrometry
      PAHs adsorbed on diesel particles with high sensitivity. 2,4,7-trinitro-9
      fluorenone and 7,7',8,8'-tetracyanoquinodimethane pi-acceptor compounds form
      charge-transfer complexes with PAHs and prevent their evaporation in the mass
      spectrometer during analysis. Moreover, the production of PAH molecular ions is
      dramatically increased by laser irradiation of these complexes at short
      wavelength (221.7 nm) and low power density (5 x 10(6) W cm(-)(2)). This
      methodology is applied for the first time to the examination of DPM collected
      during the new European driving cycle for light-duty vehicles. Differentiation
      criteria may coherently be assigned to engine operating mode (engine temperature,
      driving conditions). DPM samples can also be easily distinguished in negative
      ions according to the high sensitivity of this detection mode to sulfate
      compounds.

PMID- 15253631
TI  - Isotopic variations of Zn in biological materials.
AB  - Variations in the isotopic composition of Zn present in various biological
      materials were determined using high-resolution multicollector inductively
      coupled plasma mass spectrometry (MC-ICPMS), following digestion and purification
      by anion exchange chromatography. To correct for differences in instrumental mass
      discrimination effects between samples and standards, Cu was employed as an
      elemental spike. Complementary analyses of Zn separates by sector field ICPMS
      instruments revealed that the concentrations of the majority of potentially
      interfering elements were reduced to negligible levels. Residual spectral
      interferences resulting from (35)Cl(16)O(2)(+), (40)Ar(14)N(2)(+), and
      (40)Ar(14)N(16)O(+) could be instrumentally resolved from the (67)Zn, (68)Zn, and
      (70)Zn ion beams, respectively, during measurement by MC-ICPMS. The only other
      observed interference in the Cu and Zn mass range that could not be effectively
      eliminated by high-resolution multicollection resulted from (35)Cl(2)(+),
      necessitating modification of the sample preparation procedure to allow accurate
      (70)Zn detection. Complete duplication of the entire analytical procedure for
      human whole blood and hair, as well as bovine liver and muscle, provided an
      external reproducibility of 0.05-0.12 per thousand (2sigma) for measured
      delta(66/64)Zn, delta(67/64)Zn, and delta(68/64)Zn values, demonstrating the
      utility of the method for the precise isotopic analysis of Zn in biological
      materials. Relative to the selected Zn isotopic standard, delta(66/64)Zn values
      for biological samples varied from -0.60 per thousand in human hair to +0.56 per
      thousand in human whole blood, identifying the former material as the
      isotopically lightest Zn source found in nature to date.

PMID- 15253633
TI  - Quantification of single fluid inclusions by combining synchrotron radiation
      induced micro-X-ray fluorescence and transmission.
AB  - Fluid inclusions represent the only direct samples of ancient fluids in many
      crustal rocks; precise knowledge of their chemical composition provides crucial
      information to model paleofluid-rock interactions and hydrothermal transport
      processes. Owing to its nondestructive character, micrometer-scale spatial
      resolution, and high sensitivity, synchrotron radiation-induced micro-X-ray
      fluorescence has received great interest for the in situ multielement analysis of
      individual fluid inclusions. Major uncertainties associated with the quantitative
      analysis of single fluid inclusions arise from the inclusion depth and the volume
      of fluid sampled by the incident beam. While the depth can be extracted directly
      from the fluorescence spectrum, its volume remains a major source of uncertainty.
      The present study performed on natural and synthetic inclusions shows that the
      inclusion thickness can be accurately evaluated from transmission line scans.
      Experimental data matched numerical simulations based on an elliptical inclusion
      geometry. However, for one nonelliptical inclusion, the experimental data were
      confirmed using a computed absorption tomography reconstruction. Good agreement
      between the imaging and scanning techniques implies that the latter provides
      reliable fluid thickness values independent of the shape of the inclusion. Taking
      into consideration the incident angle, the incident beam energy, the inclusion
      fluid salinity, and the transmission measurement stability resulted in errors of
      0.3-2 microm on calculated fluid inclusion thicknesses.

PMID- 15253634
TI  - Single-step formation of a biorecognition layer for assaying histidine-tagged
      proteins.
AB  - The purpose of this work was to develop a simple procedure for the creation of a
      specific biorecognition layer for histidine-tagged (His-tagged) molecules. Such a
      layer was prepared by the spontaneous fusion of vesicles containing readily
      available plain (DOPC) and iminodiacetic acid (DOGS-NTA) phospholipids on a
      silica surface resulting in the formation of an NTA-containing supported lipid
      bilayer. The frequency surface acoustic waveguide device which supports Love
      waves was used to follow the real-time formation of the biorecognition layer. The
      mole percent of the DOGS-NTA phospholipids in the supported bilayer was optimized
      by following the kinetics of the fusion for the different NTA-containing lipids.
      Fluorescently labeled lipids were used with observations of the fluorescence
      recovery after photobleaching to confirm the presence of lipid bilayers. After
      saturating all NTA-molecules with Ni(2+), the binding of a His-tagged protein
      fragment within the concentration range of 0.04 and 0.4 mM to a 5 mol % DOGS
      NTA/DOPC was detected; binding curves were used to calculate the apparent
      association constant k(on) = 2.56 x 10(4) M(-)(1) s(-)(1), dissociation constant
      k(off) = 1.3 x 10(-)(3) s(-)(1), and equilibrium constant k(eq) = 1.97 x 10(7) M(
      )(1). The described method could find significant applications as a generic
      technique for preparing biorecognition layers for His-tagged proteins. In
      addition, the acoustic waveguide device, which provides high sensitivity together
      with flexibility in terms of the substrate material used, is shown to be an
      attractive alternative to direct optical biosensors.

PMID- 15253635
TI  - Multichannel electrochemiluminescence of luminol in neutral and alkaline aqueous
      solutions on a gold nanoparticle self-assembled electrode.
AB  - The electrochemiluminescence (ECL) behavior of luminol on a gold nanoparticle
      self-assembled electrode in neutral and alkaline pH conditions was studied under
      conventional cyclic voltammetry (CV). The gold nanoparticle self-assembled
      electrode exhibited excellent electrocatalytic property and redox reactivity to
      the luminol ECL system. In neutral solution, four ECL peaks were observed at
      0.69, 1.03, -0.45, and -1.22 V (vs SCE) on the curve of ECL intensity versus
      potential. Compared with a bulk gold electrode, two anodic and one cathodic ECL
      peaks were greatly enhanced, and one new cathodic ECL peak appeared. In alkaline
      solution, two anodic ECL peaks were obtained at 0.69 and 1.03 V, which were much
      stronger than those on a bulk gold electrode. These ECL peaks were found to
      depend on gold nanoparticles on the surface of the electrode, potential scan
      direction and range, the presence of O(2) or N(2), the pH and concentration of
      luminol solution, NaBr concentration, and scan rate. The emitter of all ECL peaks
      was identified as 3-aminophthalate by analyzing the ECL spectra. The spatial
      distribution of the luminol ECL peaks on the gold nanoparticle self-assembled
      electrode was studied by CCD. The surface state of the gold nanoparticle self
      assembled electrode was characterized by scanning electron microscopy (SEM) and
      UV-visible reflection spectra. The mechanism for the formation of these ECL peaks
      has been proposed. The results indicate that the gold nanoparticle self-assembled
      electrode could lead to novel ECL properties, and strong luminol ECL in neutral
      and alkaline solutions could be obtained on such an electrode, which is of great
      analytical potential.

PMID- 15253636
TI  - Convectively driven polymerase chain reaction thermal cycler.
AB  - We have fabricated a low-cost disposable polymerase chain reaction thermal
      chamber that uses buoyancy forces to move the sample solution between the
      different temperatures necessary for amplification. Three-dimensional, unsteady
      finite element modeling and a simpler 1-D steady-state model are used together
      with digital particle image velocimetry data to characterize the flow within the
      device. Biological samples have been amplified using this novel thermal chamber.
      Time for amplification is less than 30 min. More importantly, an analysis of the
      energy consumption shows significant improvements over current technology.

PMID- 15253637
TI  - Identification of biomarkers of whole Coxiella burnetii phase I by MALDI-TOF mass
      spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) specific biomarkers have been shown to be an effective tool for
      identifying microorganisms. In this study, we demonstrate the feasibility of
      using this technique to detect the obligate intracellular bacterium Coxiella
      burnetii, a category B bioterrorism agent. Specific biomarkers were detected in
      C. burnetii Nine Mile phase I (NMI) strain purified from embryonated egg yolk sac
      preparations. Whole organisms were applied directly to the MALDI target. MALDI
      TOF MS analysis of C. burnetii NMI grown and purified at different times and
      places revealed a group of unique, characteristic, and reproducible spectral
      markers in the mass range of 1000-25000 Da. Statistical analysis of the averaged
      centroided masses uncovered at least 24 peptides or biomarkers. Three biomarkers
      observed in the MALDI-TOF MS spectrum consistently matched proteins that had been
      previously described in C. burnetii, one of them being the small cell variant
      protein A. MALDI-TOF MS analysis of whole organisms represents a sensitive and
      specific option for characterizing C. burnetii isolates, especially when coupled
      with antigen capture techniques. The method also has potential for several
      applications in basic microbial research, including regulation of gene
      expression.

PMID- 15253639
TI  - Theoretical comparison of the band broadening in nonretained electrically and
      pressure-driven flows through an ordered chromatographic pillar packing.
AB  - Using a well-validated computational fluid dynamics simulation method, based on a
      multi-ion transport model, a detailed analysis of the differences in band
      broadening between pressure-driven (PD) and electrically driven (ED) flows
      through perfectly ordered, identical chromatographic pillar packings has been
      made. It was found that, although the eddy-diffusion band-broadening
      contributions were nearly completely absent in the considered structure, the ED
      flow still yields much smaller plate heights than the PD flow. This difference
      could be fully attributed to the different ways in which the ED and PD velocity
      profiles reshape when passing through a tortuous pore structure with undulating
      cross section. Whereas in the PD case the parabolic tip of the band front is
      continually squeezed and extended each time it passes a pore constriction, the ED
      flow displays some kind of band front restoring mechanism, with which the fluid
      elements of the band front are (at least partly) laterally re-aligned after each
      pore constriction passage. This could be clearly visualized from a series of step
      by-step images of the progression of a sharply "injected" species band moving
      through the packing under ED and PD conditions.

PMID- 15253638
TI  - A nucleic acid biosensor for gene expression analysis in nanograms of mRNA.
AB  - An ultrasensitive nucleic acid biosensor for direct detection of genes in mRNA
      extracted from animal tissues is described. It is based on amperometric detection
      of a target gene by forming an mRNA/redox polymer bilayer on a gold electrode.
      The mRNA was directly labeled with cisplatin-biotin conjugates through
      coordinative bonds with purine bases in the mRNA molecules. A subsequent binding
      of glucose oxidase-avidin conjugates to the labeled mRNA and the introduction of
      a poly(vinylimidazole-co-acrylamide) partially imidazole-complexed with
      [Os(bpy)(2)(im)] (bpy = 2,2'-bipyridine, im = imidazole) redox polymer
      overcoating to the electrode allowed for electrochemical detection of the
      oxidation current of glucose in solution. Depending on individual genes,
      detection limits of subfemtograms were achieved. As compared to a sandwich-type
      assay, the sensitivity was improved by as much as 25-fold through the
      incorporation of multiple enzyme labels to the mRNA molecules. Less than 2-fold
      gene expression difference was unambiguously differentiated in as little as 5.0
      ng of mRNA. With the greatly improved sensitivity, at least 1000-fold more
      sensitive than fluorescence-based techniques, the amount of mRNA needed in the
      assay was cut down from microgram to nanogram levels.

PMID- 15253640
TI  - A wireless, remote query glucose biosensor based on a pH-sensitive polymer.
AB  - This paper describes a wireless, remote query glucose biosensor using a
      ribbonlike, mass-sensitive magnetoelastic sensor as the transducer. The glucose
      biosensor is fabricated by first coating the magnetoelastic sensor with a pH
      sensitive polymer and upon it a layer of glucose oxidase (GOx). The pH-responsive
      polymer swells or shrinks, thereby changing mass, respectively, in response to
      increasing or decreasing pH values. The GOx-catalyzed oxidation of glucose
      produces gluconic acid, inducing the pH-responsive polymer to shrink, which in
      turn decreases the polymer mass. In response to a time-varying magnetic field, a
      magnetoelastic sensor mechanically vibrates at a characteristic resonance
      frequency, the value of which inversely depends on sensor mass loading. As the
      magnetoelastic films are magnetostrictive, the vibrations launch magnetic flux
      that can be remotely detected using a pickup coil. Hence, changes in the
      resonance frequency of a passive magnetoelastic transducer are detected on a
      remote query basis, without the use of physical connections to the sensors.The
      sensitivity of the glucose biosensors decreases with increasing ionic strength;
      at physiological salt concentrations, 0.6 mmol/L of glucose can be measured. At
      glucose concentrations of 1-10 mmol/L, the biosensor response is reversible and
      linear, with the detection limit of 0.6 mmol/L corresponding to an error in
      resonance frequency determination of 20 Hz. Since no physical connections between
      the sensor and the monitoring instrument are required, this sensor can
      potentially be applied to in vivo and in situ measurement of glucose
      concentrations.

PMID- 15253641
TI  - Capillary sieving electrophoresis/micellar electrokinetic capillary
      chromatography for two-dimensional protein fingerprinting of single mammalian
      cells.
AB  - We have developed a two-dimensional capillary electrophoresis method for the
      study of protein expression in single mammalian cells. The first-dimension
      capillary contains an SDS-pullulan buffer system to perform capillary sieving
      electrophoresis, which separates proteins based on molecular weight. The second
      dimension capillary contains an SDS buffer for micellar electrokinetic capillary
      chromatography. After a 6-min-long preliminary separation, fractions from the
      first capillary are successively transferred to a second capillary, where they
      undergo further separation by MECC. Over 100 transfers and second-dimension
      separations are performed over an approximately 3.5-h-long period. We demonstrate
      this technology by generating protein fingerprints from single native MC3T3-E1
      osteoprogenitor cells and MC3T3-E1 cells transfected with the human transcription
      regulator TWIST. We also present single-cell protein fingerprints from MCF-7
      breast cancer cells before and following treatment to induce apoptosis.

PMID- 15253642
TI  - Electrosonic spray ionization. A gentle technique for generating folded proteins
      and protein complexes in the gas phase and for studying ion-molecule reactions at
      atmospheric pressure.
AB  - Electrosonic spray ionization (ESSI), a variant on electrospray ionization (ESI),
      employs a traditional micro ESI source with supersonic nebulizing gas. The high
      linear velocity of the nebulizing gas provides efficient pneumatic spraying of
      the charged liquid sample. The variable electrostatic potential can be tuned to
      allow efficient and gentle ionization. This ionization method is successfully
      applied to aqueous solutions of various proteins at neutral pH, and its
      performance is compared to that of the nanospray and micro ESI techniques.
      Evidence for efficient desolvation during ESSI is provided by the fact that the
      peak widths for various multiply charged protein ions are an order of magnitude
      narrower than those for nanospray. Narrow charge-state distributions compared to
      other ESI techniques are observed also; for most of the proteins studied, more
      than 90% of the protein ions can be accumulated in one charge state using ESSI
      when optimizing conditions. The fact that the abundant charge state is normally
      as low or lower than that recorded by ESI or nanospray indicates that folded
      protein ions are generated. The sensitivity of the ionization technique to high
      salt concentrations is comparable to that of nanospray, but ESSI is considerably
      less sensitive to high concentrations of organic additives such as glycerol or 2
      amino-2-(hydroxymethyl)-1,3-propanediol (Tris base). Noncovalent complexes are
      observed in the case of myoglobin, protein kinase A/ATP complex, and other
      proteins. The extent of dissociation of protein ions in ESSI is comparable to or
      even smaller than that in the case of nanospray, emphasizing the gentle nature of
      the method. The unique features of ESSI are ascribed to very efficient spraying
      and the low internal energy supplied to the ions. Evidence is provided that the
      method is capable of generating fully desolvated protein ions at atmospheric
      pressure. This allows the technique to be used for the study of ion-molecule
      reactions at atmospheric pressure and examples of this are shown.

PMID- 15253643
TI  - Electrochemical detection of single-nucleotide mismatches: application of M-DNA.
AB  - The detection of a single-nucleotide mismatch in unlabeled duplex DNA by
      electrochemical methods is presented. Impedance spectroscopy is used to
      characterize a perfect duplex monolayer and three DNA monolayers differing in the
      position of the mismatch. The monolayers were studied as B-DNA (normal duplex
      DNA) and after conversion to M-DNA (a metalated duplex). Modeling of the
      impedance data to an equivalent circuit provides parameters that are useful in
      discriminating the four monolayer configurations. The resistance to charge
      transfer, R(CT), was lower for all duplexes after conversion to M-DNA. Contrary
      to expectations, R(CT) was also found to decrease for duplexes containing a
      mismatch. However, R(CT) was found to be diagnostic for mismatch detection. In
      particular, the difference in R(CT) between B- and M-DNA (deltaR(CT)) decreased
      from 190(22) omega.cm(2) for a perfectly matched duplex to 95(20), 30(20), and
      85(20) omega.cm(2) for a mismatch at the top (distal), middle, and bottom
      (proximal) positions of the monolayer with respect to the gold surface. Further,
      a method to form loosely packed single-stranded (ss)-DNA monolayers by duplex
      dehybridization that is able to rehybridize to target strands is presented.
      Rehybridization efficiencies were in the range of 40-70%. Under incomplete
      hybridization conditions, the R(CT) was the same for matched and mismatched
      duplexes under B-DNA conditions. However, deltaR(CT) between B- and M-DNA, under
      incomplete hybridization, still provided a distinction. The deltaR(CT) for a
      perfect duplex was 76(12) omega.cm(2), whereas a mismatch in the middle of the
      sequence yielded a deltaR(CT) value of 30(15) omega.cm(2). The detection limit
      was measured and the impedance methodology reliably detected single DNA base pair
      mismatches at concentrations as low as 100 pM.

PMID- 15253644
TI  - Aptamer-based sensor arrays for the detection and quantitation of proteins.
AB  - Aptamer biosensors have been immobilized on beads, introduced into micromachined
      chips on the electronic tongue sensor array, and used for the detection and
      quantitation of proteins. Aptamer chips could detect proteins in both capture and
      sandwich assay formats. Unlike most protein-based arrays, the aptamer chips could
      be stripped and reused multiple times. The aptamer chips proved to be useful for
      screening aptamers from in vitro selection experiments and for sensitively
      quantitating the biothreat agent ricin.

PMID- 15253645
TI  - Ultraviolet surface plasmon-coupled emission using thin aluminum films.
AB  - Surface plasmon-coupled emission (SPCE) is the directional radiation of light
      into a substrate due to excited fluorophores above a thin metal film. To date,
      SPCE has only been observed with visible wavelengths using silver or gold films.
      We now show that SPCE can be observed in the ultraviolet region of the spectrum
      using thin (20 nm) aluminum films. We observed directional emission in a quartz
      substrate from the DNA base analogue 2-aminopurine (2-AP). The SPCE radiation
      occurs within a narrow angle at 59 degrees from the normal to the hemicylindrical
      prism. The excitation conditions precluded the creation of surface plasmons by
      the incident light. The directional emission at 59 degrees is almost completely p
      polarized, consistent with its origin from surface plasmons due to coupling of
      excited 2-AP with the aluminum. The emission spectra and lifetimes of the SPCE
      are those characteristic of 2-AP. Different emission wavelengths radiate at
      slightly different angles on the prism providing intrinsic spectral resolution
      from the aluminum film. These results indicate that SPCE can be used with
      numerous UV-absorbing fluorophores, suggesting biochemical applications with
      simultaneous surface plasmon resonance and SPCE binding assays.

PMID- 15253646
TI  - Development of a protein chip: a MS-based method for quantitation of protein
      expression and modification levels using an immunoaffinity approach.
AB  - Protein chip technology permits analysis of the expression and modification
      status of numerous targeted proteins within a single experiment, mainly through
      the use of antibody-based microarrays. Despite recent improvements in these
      protein chips, their applications are still limited for a variety of reasons,
      which include technical challenges in fabrication of the antibody chips as well
      as the very low specificity achieved by current detection methods. We have
      developed a unique approach for relative and/or absolute quantitation of protein
      expression and modification based on the capture of epitope peptides on affinity
      beads, which can be used to develop a mass-spectrometry-based protein chip
      technology. This new method, which utilizes antibodies immobilized on beads for
      the capture of target peptides, instead of proteins, eliminates many of the
      problems previously associated with protein chips. We present here several proof
      of-principle experiments examining model peptides by this technique. These
      experiments show that the method is capable of (i). detecting peptides bound to a
      single antibody bead, (ii). detecting peptides at low (fmol) levels, (iii).
      producing MS/MS data of suitable quality for protein identification via database
      searching or de novo sequencing, (iv). quantitating peptides affinity-bound to
      antibody beads, (v). specifically detecting target peptides in complex mixtures
      over wide dynamic ranges, and (vi) is compatible with a microarray format for
      high-throughput analysis. Because our novel method uses antibody beads instead of
      a derivatized capture surface, and peptides instead of proteins for affinity
      capture, it can overcome many of the pitfalls of previous protein chip
      fabrications. Therefore, this method offers an improved approach to protein chip
      technology that should prove useful for diagnostics and drug development
      applications.

PMID- 15253647
TI  - Detection of approximately 10(3) copies of DNA by an electrochemical enzyme
      amplified sandwich assay with ambient O(2) as the substrate.
AB  - The electrochemical sandwich-type, enzyme-amplified assay of Zhang, Kim, and
      Heller (Anal. Chem. 2003, 75, 3267-3269) was simplified by replacing the
      amplifying horseradish peroxidase with bilirubin oxidase (BOD). BOD catalyzes the
      reduction of ambient O(2) to water and obviates the need for adding H(2)O(2).
      Femtomolar (10(-)(15) M) concentrations of DNA were detected at a 10-microm
      diameter tip of a carbon fiber electrode. Correspondingly, a few thousand copies
      of DNA were detected in approximately 5-microL samples. The sandwich is formed in
      an electron-conducting redox hydrogel, to the polymer of which a DNA capture
      sequence is bound. Capture of the analyte DNA and its hybridization with a BOD
      labeled complementary DNA sequence, electrically connects the BOD label to the
      electron-conducting redox polymer, which is in electrical contact with the
      electrode. Placing the BOD in contact with the redox polymer thus converts the
      noncatalytic base layer into a catalyst for the electroreduction of O(2) to water
      at +0.12 V (vs Ag/AgCl) (Figure 1). In an exemplary assay, approximately 3000
      copies of the iron transporting sequence of the sit gene of Shigella flexneri
      were detected without PCR amplification.

PMID- 15253648
TI  - Dynamic gene expression profiling using a microfabricated living cell array.
AB  - We describe the development of a microfluidic platform for continuous monitoring
      of gene expression in live cells. This optically transparent microfluidic device
      integrates high-throughput molecular stimulation with nondestructive monitoring
      of expression events in individual living cells, hence, a living cell array
      (LCA). Several concentrations of a soluble molecular stimulus are generated in an
      upstream microfluidic network and used to stimulate downstream reporter cells,
      each containing a green fluorescence reporter plasmid for a gene of interest.
      Cellular fluorescence is continuously monitored and quantified to infer the
      expression dynamics of the gene being studied. We demonstrate this approach by
      profiling the activation of the transcription factor NF-kappaB in HeLa S3 cells
      in response to varying doses of the inflammatory cytokine TNF-alpha. The LCA
      platform offers a unique opportunity to simultaneously control dynamic inputs and
      measure dynamic outputs from adherent mammalian cells in a high-throughput
      fashion. This approach to profiling expression dynamics, in conjunction with
      complementary techniques such as DNA microarrays, will help provide a more
      complete picture of the dynamic cellular response to diverse soluble stimuli.

PMID- 15253649
TI  - Absolute quantification of specific proteins in complex mixtures using visible
      isotope-coded affinity tags.
AB  - The identification of proteins in complex mixtures is most useful when
      quantitative information is also obtained. We describe a new type of protein
      tagging reagent called the visible isotope-coded affinity tag (VICAT) which
      allows the absolute amount of a target protein or proteins to be quantified in a
      complex biological sample such as a eukaryotic cell lysate. VICAT reagents tag
      thiol groups of cysteines or thioacetylated amino groups and introduce into the
      tryptic peptide a biotin affinity handle, a visible moiety for tracking the
      chromatographic location of the target peptide by a method other than mass
      spectrometry, a photocleavable linker for removing a portion of the tag, and an
      isotope tag for distinguishing sample and internal standard peptides. We
      demonstrate the use of VICAT reagents together with isoelectric focusing of
      peptides on an immobilized gel strip followed by combined micro-liquid
      chromatography/electrospray ionization mass spectrometry operating in selected
      reaction monitoring mode to determine the absolute abundance of a specific
      protein, human group V phospholipase A(2), in eukaryotic cell lysates. It is
      found that human lung macrophages contain 66 fmol of this protein per 100 microg
      of cell protein. Western blot analysis of human group V phospholipase A(2) in
      macrophages gave inconclusive data. VICAT reagents should be useful for numerous
      applications including the analysis of candidate disease markers in complex
      mixtures such as serum.

PMID- 15253650
TI  - Nanoarrays: a method for performing enzymatic assays.
AB  - Conventional enzymatic assays for alcohol dehydrogenase, pyruvate kinase, and
      enolase performed in 96-well microtiter plates were compared with assays
      monitored in 25-well nanoarrays. All miniaturized reactions could be performed in
      maximum volumes of 6.3-8 nL and were read out with a conventional fluorescence
      microscope system equipped with a scientific grade CCD camera. Substrate and
      cofactor were already present inside the wells after having been presprayed, or
      they were applied in solution to the wells of the nanoarray shortly before the
      assays started. For all of the assays, commercially available enzymes and enzymes
      present in cell-free extracts were used. Assays carried out in premixed
      nanoarrays gave results comparable to those performed in presprayed nanoarrays.
      Enzyme activities determined in nanoarrays by using two different methods were in
      good agreement with assays performed in microtiter plates. Also, good
      correspondence was found between expected and observed enzyme levels. In short,
      enzymatic assays performed in premixed and in particular in presprayed nanoarrays
      are a promising low-volume and low-reagent- and sample-consuming alternative to
      current methodology and could find applications in many different areas of
      analytical chemistry.

PMID- 15253651
TI  - Analytical performance of a venturi device integrated into an electrospray
      ionization fourier transform ion cyclotron resonance mass spectrometer for
      analysis of nucleic acids.
AB  - A voltage-assisted venturi device modeled after an industrial air amplifier was
      used to improve the ion transmission efficiency of a 16.2 kDa oligonucleotide and
      a 53-mer PCR product in the high-pressure region between an electrospray
      ionization (ESI) emitter and the sampling orifices of two Fourier transform ion
      cyclotron resonance mass spectrometers (FT-ICR-MS). The venturi device increased
      the total ion abundance of the oligonucleotide and the PCR product by more than 6
      fold relative to the best achievable signal without the device. Furthermore, the
      average charge states of the oligonucleotide and PCR product shifted from 12.5-
      to 14.5- and 10.9- to 12.6-, respectively, with the addition of the venturi
      device. Specific to FT-ICR mass spectrometry, this increase in the charge state
      directly translates to an increase in theoretical mass resolving power (>10000
      full width half-maximum for the results presented here at 7 T). Adduction was
      still observed while using the device, suggesting that it is "soft" relative to
      other high-pressure ion focusing methods.

PMID- 15253652
TI  - Studying rat brain neurochemistry using nanoprobe NMR spectroscopy: a
      metabonomics approach.
AB  - In the present experiments, in vivo microdialysis techniques together with
      nanoprobe NMR spectroscopy were used to evaluate the neurochemical environment of
      the rat frontal cortex. Metabonomics techniques of data reduction and pattern
      recognition were used to examine whether collected neurochemicals were sensitive
      to tetrodotoxin (TTX), a neurotoxin that when infused into discrete brain regions
      can help distinguish between the neuronal versus glial origin of neurochemicals
      in cerebrospinal fluid microdialysate. (1)H NMR spectra recorded on samples
      collected from the rat frontal cortex before and after an intracortical TTX
      infusion (10 microM for 60 min) were subjected to multivariate statistical
      analysis. Glutamate, isoleucine, valine, alanine, and alpha- and beta
      hydroxybutyrate were found to have decreased concentrations after the addition of
      TTX, suggesting that their release is likely from cortical neurons. In contrast,
      lactate, formate, acetate, glucose, creatinine, pyruvate, and other
      neurochemicals remained unchanged following local application of TTX. The present
      findings extend our previous work combining the analytical technology of small
      volume nanoprobe NMR spectroscopy with in vivo microdialysis in freely moving
      animals and show that it is possible to apply metabonomics methodology to this
      important class of biofluid to monitor changes in neurochemical composition of
      the rat brain.

PMID- 15253653
TI  - Electrochemical investigation of dopamine at the water/1,2-dichloroethane
      interface.
AB  - Dopamine is an important neurotransmitter in mammalian central and peripheral
      nervous systems and is also a medicament to cure some neuropsychosis. In this
      work, ion transfer (IT), facilitated ion transfer (FIT) of protonated dopamine,
      and electron transfer (ET) between dopamine and ferrocene are investigated at the
      water/1,2-dichloroethane (W/DCE) interface. The IT and FIT reactions of
      protonated dopamine can be observed simultaneously within the same potential
      window. The experimental results demonstrate that dibenzo-18-crown-6, dibenzo-24
      crown-8, and benzo-15-crown-5 work well with the protonated dopamine. The
      amperometric detection of dopamine based on either the IT or the FIT of
      protonated dopamine can get rid of the interference of ascorbic acid, and the
      lowest concentration that can be determined is approximately 0.05 microM by
      differential pulse voltammetry. For the ET reaction, its kinetics can be
      evaluated by scanning electrochemical microscopy, and the results show that the
      relationship between rate constants and driving force at the unmodified W/DCE
      interface obeys the Butler-Volmer equation in a rather wide potential region.
      When the W/DCE interface is modified by egg lecithin, the ET rate constants
      decrease with increasing concentration of egg lecithin, which indicates that egg
      lecithin hinders the ET reaction. When the driving force is increased to a
      certain degree, the linear relationship between ET rate constants and the driving
      force is distorted. These results will be helpful to understand both the
      pharmacodynamics and the neural signal transmission mechanism of dopamine at
      biological membranes and also provide a novel way to detect dopamine.

PMID- 15253654
TI  - Pore-bridging poly(dimethylsiloxane) membranes as selective interfaces for vapor
      phase chemical sensing.
AB  - A new kind of polymer-based sensor is described in which the experimental
      parameters controlling selectivity and sensitivity are decoupled. The sensor is
      based on a surface acoustic wave (SAW) gravimetric transducer modified with a
      high-surface-area, nanoporous alumina coating. A very thin ( approximately 40 nm)
      poly(dimethylsiloxane) (PDMS) coating resides atop the porous alumina structure.
      In this configuration, the total surface area of the nanoporous alumina coating
      controls the sensitivity of the device, while the chemical properties of the PDMS
      membrane control selectivity. In conventional polymer-based sensors, the polymer
      plays the dual role of controlling both selectivity (via the chemical composition
      of the coating) and sensitivity (via the volume of the film). In this paper, we
      show that PDMS acts as a chemically selective gate that absorbs polar and
      nonpolar VOCs but does not transport these analytes to the underlying pore
      volume. In contrast, water vapor is absorbed by the PDMS to a very minor extent
      but is easily transported through it to the underlying walls of the porous
      substructure. Specifically, there was little difference in the mass-loading
      response arising from polar and nonpolar VOCs dosed onto planar and nanoporous
      SAW devices modified with PDMS. In contrast, SAW devices having nanoporous
      coatings responded up to 24 times more selectively to water than planar sensors
      modified identically.

PMID- 15253655
TI  - Quantitative measurements of dielectric spectra with microdielectric fringe
      effect sensors.
AB  - The parallel-plate method is a gold standard for measuring dielectric properties
      of materials. However, it requires sampling of the material under testing (MUT),
      which makes it less suitable for real time, dynamic, and in situ measurements.
      The alternative to the parallel-plate method is to use the microdielectric fringe
      effect (FE) sensors, which can be placed inside the process or laboratory
      equipment to provide rapid, on-line, and noninvasive characterization of the
      dielectric properties. An additional potential advantage of the FE measurements
      is the ability to obtain spatially localized and interfacial measurements, which
      may be important in some applications. Unfortunately, interpretation of the FE
      sensor measurements is difficult because of the spatial nonuniformity of the
      electrical excitation field created by the FE sensor and the extraneous
      contributions from the sensor substrate and unknown stray elements. The objective
      of this study is to summarize the theoretical basis of the dielectric
      measurements using planar interdigitated sensors and to use it in the development
      of a new method for obtaining quantitative measurements with FE sensors. As the
      first step, the basic correlation between the impedance measurements obtained
      with the FE sensor and the dielectric properties of the MUT is elucidated. The
      theoretical results are then used to analyze the contribution of the sensor
      substrate and unknown stray components to the overall measurements. A novel
      calibration method to eliminate extraneous contributions is then proposed. The
      application example demonstrates the application of the developed method to the
      measurement of the dielectric permittivities of a polydispersed cis-polyisoprene
      samples. The results are compared with those obtained using the parallel-plate
      measurements and show excellent agreement. Experimental comparison with the
      alternative calibration methods is also performed, indicating significant
      improvement in accuracy of dielectric measurements over a broad range of
      frequencies.

PMID- 15253656
TI  - Effect of the phase volume ratio on the potential of a liquid-membrane ion
      selective electrode.
AB  - Two-phase liquid system IA(w)|IX(o) comprising the interface between the aqueous
      solution (w) of uni-univalent electrolyte IA and an organic solvent solution (o)
      of a uni-univalent electrolyte IX with the common cation I(+) is considered as a
      simple model of a liquid-membrane ion-selective electrode (ISE). Taking into
      account the electroneutrality and mass balance conditions, the equilibrium
      Galvani potential difference (pd) between the aqueous and organic phases, phi =
      phi(w) - phi(o), is calculated numerically as a function of the ratio of the
      initial electrolyte concentrations, x = / = 10(-)(4)-10(4), for the selected
      values of the phase volume ratio r = V(o)/V(w) = 10(-)(3), 1, and 10(3), and the
      standard ion transfer potentials of the present ions ranging from -0.5 to 0.5 V.
      Numeric results corroborate the symbolic expressions derived for the cases when
      X(-) and A(-) are extremely lipophilic and hydrophilic ions, respectively, or
      when the concentration ratio x is extremely large or small. In contrast to the
      extraction system, where both electrolytes are initially present in the aqueous
      phase, the effect of the phase volume ratio on the equilibrium pd in the ISE
      model is rather weak, unless the counterions X(-) and A(-) differ little in their
      lipophilicity from the target ion I(+). It is shown that both the ISE and
      extraction model exhibit the Nernstian behavior only in a limited range of the
      concentration ratio x depending on the value of the standard ion transfer
      potentials of the counterions. When this ratio is extremely large or small,
      equilibrium pd approaches the limiting value given by the distribution potential
      of the electrolyte IA or IX, respectively. Similar conclusions can be drawn for
      the two-phase liquid system AI(w)|XI(o) with the common anion I(-).

PMID- 15253657
TI  - Development of a whole-cell-based biosensor for detecting histamine as a model
      toxin.
AB  - A novel whole-cell potentiometric biosensor for screening of toxins has been
      developed. The constructed biosensor consists of a confluent monolayer of human
      umbilical vein endothelial cells (HUVECs) attached to an ion-selective cellulose
      triacetate (CTA) membrane modified with a covalently attached RGD (arginine
      glycine-aspartic acid) peptide sequence. When the HUVECs form a confluent
      monolayer, ion transport is almost completely inhibited, thereby reducing the
      response of the ion-selective electrode (ISE). When the monolayer is exposed to
      agents that increase its permeability (e.g., toxins), ions can diffuse through
      the membrane, and a potential response from the ISE is achieved. Histamine, a
      model toxin that increases the permeability of HUVEC monolayers, was used in this
      study. When the cell-based membranes are exposed to varying concentrations of
      histamine, the overall response increases with increasing histamine
      concentration. Thus, the measured potential is an indirect measurement of the
      histamine concentration. Further experiments were performed for a similar
      molecule, l-histidine, to test for selectivity. The cell permeability was
      unaffected by l-histidine, and the sensor response remained unchanged. This type
      of sensor should find multiple applications in medical, food, and environmental
      fields and in homeland security.

PMID- 15253658
TI  - Electrochemistry and electrocatalytic activities of superoxide dismutases at gold
      electrodes modified with a self-assembled monolayer.
AB  - In this article, the electrochemical properties and electrocatalytic activity of
      three kinds of superoxide dismutases (SODs), that is, bovine erythrocyte copper
      zinc superoxide dismutase (Cu/Zn-SOD), iron superoxide dismutase from Escherichia
      coli (Fe-SOD), and manganese superoxide dismutase from E. coli (Mn-SOD), in the
      SOD family were studied. It was revealed that the direct electron transfer of the
      three kinds of SODs could be efficiently promoted by a self-assembled monolayer
      (SAM) of 3-mercaptopropionic acid (MPA) confined on a gold electrode. The
      electrochemical properties of the SODs at the MPA-SAM electrode vary with the
      sort of SOD with respect to the formal potential, reversibility of electrode
      reactions, kinetic parameters, and pH dependence, suggesting different mechanisms
      for the electrode reactions of the individual SODs. A combination of the
      facilitated direct electron transfer and the bifunctional enzymatic catalytic
      activities of the SODs via a redox cycle of their active metals substantially
      offered a flexible electrochemical route to determination of O(2)(*)(-) where
      O(2)(*)(-) can be sensed with the SOD-based biosensors in both anodic and
      cathodic polarizations. Such an intrinsic feature of the SOD-based biosensors
      successfully enabled a sensitive determination scheme for O(2)(*)(-) free from
      the interference from some coexisting electroactive species, such as ascorbic
      acid (AA) and uric acid (UA). Further potential applications for in vivo
      determination of O(2)(*)(-) is also suggested.

PMID- 15253659
TI  - Ultrasensitive detection of DNA sequences in solution by specific enzymatic
      labeling.
AB  - We present a newly developed technique for the direct detection of very low
      concentrations of specific nucleic acid sequences in homogeneous solution based
      on a polymerase extension reaction. This method consists of synthesizing a highly
      fluorescent nucleic acid reporter molecule using a sequence of the target as a
      template. Synthesis of the reporter molecule is accomplished by hybridizing a
      short complementary oligonucleotide primer to the target and extending the
      reporter using a polymerase and free nucleotides. One of these nucleotides is
      partially labeled with a fluorophore. The reaction sample is then flowed through
      the capillary cell of a single molecule detector. Detection of the reporter
      signifies the presence of the target being sought. Under carefully selected
      conditions, fluorescence from the reporter molecule is much stronger than that of
      the free nucleotide background over the detection time. We have derived practical
      equations that allow us to determine an optimal range of values for the relative
      reporter and free-nucleotide concentrations. This method allows for the rapid,
      direct detection of individual targets at femtomolar concentrations without the
      use of an amplification procedure, such as the polymerase chain reaction.

PMID- 15253660
TI  - Fluorescence labeling of human rhinovirus capsid and analysis by capillary
      electrophoresis.
AB  - The capsid of human rhinovirus serotype 2, consisting of four viral proteins, was
      fluorescence-labeled with fluorescein isothiocyanate and analyzed by capillary
      electrophoresis using UV and laser-induced fluorescence detection. Heat
      denaturation, proteolytic digestion, and receptor binding were applied for
      confirmation of the identity of the peak with the labeled virus. Incomplete
      derivatization with the fluorophore preserved the affinity of the virus for its
      receptor, indicating that its cell entry pathway is unperturbed by this chemical
      modification; indeed, an infectivity assay confirms that the labeled virus
      samples are infectious. The results show that fluorescence labeling of the viral
      capsid might lead to a valuable probe for studying infection processes in the
      living cell.

PMID- 15253661
TI  - Entrapment of Src protein tyrosine kinase in sugar-modified silica.
AB  - A novel sugar-modified silica has been used to entrap for the first time a
      protein tyrosine kinase (PTK). Silane precursors bearing covalently attached
      gluconamide moieties were used in combination with the biocompatible precursor
      diglycerylsilane (DGS) to generate sol-gel derived silica that was able to
      encapsulate highly active Src PTK and preserve the activity of the enzyme over
      multiple uses. The relative activity of the enzyme was assayed using a LANCE
      based fluorescence resonance energy transfer method involving time-gated
      detection of fluorescence from a europium labeled antiphosphotyrosine antibody
      and Cy5 labeled streptavidin upon mutual binding to biotinylated phosphopeptides.
      Using this detection method, with the antibody and streptavidin external to the
      sol-gel matrix, it was possible to detect the phosphorylation of peptides with
      molecular weights of up to 2300 Da using the entrapped enzyme in N-(3
      triethoxysilylpropyl)gluconamide (GLTES) doped glasses. Src kinase-doped glasses,
      derived from precursors such as tetramethyl orthosilicate, tetraethyl
      orthosilicate, or DGS that did not contain GLTES, provided no detectable enzyme
      activity. The addition of 1 mM ATP to the GLTES/DGS sol before the encapsulation
      of the protein increased the activity of the enzyme in the resulting gel, likely
      through a ligand-based stabilization mechanism. The use of such a system for
      determination of PTK activity and inhibition is demonstrated, setting the stage
      for the development of chromatographic and microarray based methods for the
      screening of kinase inhibitors.

PMID- 15253662
TI  - Increasing the negative charge of a macroanion in the gas phase via sequential
      charge inversion reactions.
AB  - Protonated and deprotonated biological molecules in the gas phase play an
      important role in life sciences research. The structural information accessible
      from the ions is highly dependent upon their charge states. Therefore, it is
      desirable to develop means for increasing absolute charge states, particularly
      for ionization methods, such as MALDI, that yield relatively low charge ions. The
      work presented here demonstrates the formation of a doubly deprotonated
      polypeptide or oligonucleotide ion (dianion) from a singly deprotonated analogue
      via two sequential ion/ion proton-transfer reactions involving charge inversion.
      The high exoergicity and the large cross section arising from the long-range
      attractive Coulomb potential of ion/ion reactions make this process plausible. In
      this example, an overall efficiency of conversion of singly charged ions to
      doubly charged ions of roughly 8% for polypeptide was noted while lower
      efficiency (roughly 2%) observed with an oligonucleotide is likely due to a
      greater degree of neutralization. No other approach to increasing the net
      negative charge of an anion in the gas phase has as yet been reported.

PMID- 15253663
TI  - A model for random sampling and estimation of relative protein abundance in
      shotgun proteomics.
AB  - Proteomic analysis of complex protein mixtures using proteolytic digestion and
      liquid chromatography in combination with tandem mass spectrometry is a standard
      approach in biological studies. Data-dependent acquisition is used to
      automatically acquire tandem mass spectra of peptides eluting into the mass
      spectrometer. In more complicated mixtures, for example, whole cell lysates, data
      dependent acquisition incompletely samples among the peptide ions present rather
      than acquiring tandem mass spectra for all ions available. We analyzed the
      sampling process and developed a statistical model to accurately predict the
      level of sampling expected for mixtures of a specific complexity. The model also
      predicts how many analyses are required for saturated sampling of a complex
      protein mixture. For a yeast-soluble cell lysate 10 analyses are required to
      reach a 95% saturation level on protein identifications based on our model. The
      statistical model also suggests a relationship between the level of sampling
      observed for a protein and the relative abundance of the protein in the mixture.
      We demonstrate a linear dynamic range over 2 orders of magnitude by using the
      number of spectra (spectral sampling) acquired for each protein.

PMID- 15253664
TI  - Flexing the electrified meniscus: the birth of a jet in electrosprays.
AB  - Spraying of liquids through an electrified meniscus has become a method of choice
      to produce ions from large biomolecules. Using mass spectrometry, the generated
      ions can be analyzed to provide detailed information on their composition and
      structure. This technique enables high-throughput protein analysis that is a
      prerequisite for answering the questions presented by proteomics. In this report,
      Taylor cone deformations are shown to play a central role in the mechanism of
      electrostatic spraying. Spontaneous spray current oscillations are known to exist
      in most electrospray regimes and affect the stream of ions introduced into the
      mass spectrometer. Fast time-lapse imaging of the Taylor cone throughout its
      evolution indicates the presence of a nodal line and standing waves on its
      surface. Four phases of the cone pulsation cycle (liquid accumulation, cone
      formation, ejection of a jet, relaxation) are established. Based on image
      analysis, apex velocities, curvatures, and opening angles are determined. During
      jet ejection, the apex velocity and the curvature exhibit singularities.
      Furthermore, the pulsation frequencies of the Taylor cone deformations are
      determined using Fourier analysis of light refraction measurements. The
      oscillation frequency of the electrospray current collected by the counter
      electrode shows close correlation to the cone deformations, providing the first
      direct evidence that links spray current oscillations to Taylor cone pulsation.
      Thus, monitoring the oscillation frequency throughout the spraying process and
      adjusting the spray parameters can be used to stabilize the spray. Furthermore,
      synchronizing the injection of ions in time-of-flight systems with the
      spontaneous spray oscillations may improve the signal-to-noise ratio in the
      collected mass spectra.

PMID- 15253665
TI  - Determination of saikosaponin derivatives in Radix bupleuri and in
      pharmaceuticals of the chinese multiherb remedy xiaochaihu-tang using liquid
      chromatographic tandem mass spectrometry.
AB  - Saikosaponins are bioactive oleanane saponins derived from the Chinese medicinal
      herb Radix bupleuri ("chaihu" in Chinese). An LC-MS/MS-based method has been
      developed for characterization and quantification of 15 saikosaponin derivatives
      (saikosaponin a, saikosaponin b(1), saikosaponin g, saikogenin A, saikogenin H,
      saikosaponin c, saikosaponin h, saikosaponin i, prosaikogenin C(2), prosaikogenin
      B(2), saikogenin C, saikogenin B, saikosaponin d, saikosaponin b(2), and
      saikogenin D) in one chromatographic run. Optimization of the ionization process
      was performed with electrospray and atmospheric pressure chemical ionization
      techniques in both positive and negative ion modes. Negative ion ESI was adopted
      for generation of the precursor deprotonated molecules to achieve the best
      ionization sensitivity for the analytes. In addition, the most abundant fragment
      ion was chosen for each analyte to give the best CID sensitivity. Because some of
      the saponin derivatives are isomeric, complete resolution for the whole analytes
      was achieved both chromatographically and mass spectroscopically. Furthermore,
      optimal internal standard was successfully discovered for determination of the
      analytes by making use of a combinatorial chemistry approach. Good linearity over
      the range approximately 1.65 or 4.98 to 1200 ng/mL for the analytes was observed.
      The intraday accuracy and precision at nominal low, intermediate, and high
      concentration varied between 0.8 and 11.8% and between 80 and 116%, respectively,
      whereas those for interday assay were between 1.1 and 15.5% and between 86 and
      119%, respectively. The lower limits of quantitation for the test compounds were
      approximately 16.5 to 49.4 pg on-column. The new method offered higher
      sensitivity and greater specificity than previously reported LC methods. After
      the validation, the applicability of the method for determination of these
      chemicals present in a variety of crude chaihu roots and in different brands of
      the Chinese multiherb remedy Xiaochaihu-tang (or Shosaiko-to) extract granules
      has been demonstrated. The sensitivity and specificity of the technique will be
      the basis of a method for the accurate quantification of the saikosaponin
      derivatives in biomatrixes.

PMID- 15253666
TI  - Characterization of epoxy resin-based anion-responsive polymers: applicability to
      chloride sensing in physiological samples.
AB  - The potentiometric properties of an epoxy resin-based anion-responsive polymer
      and its feasibility as a chloride sensing membrane are described. The response
      mechanism of the epoxy resin-based membrane is studied by varying the types and
      contents of epoxy components (e.g., resin, hardener, diluent, and plasticizer).
      It is found that epoxy resins cured with polyamine-type hardeners have excellent
      characteristics as chloride-sensing membranes, in terms of their selectivity,
      stability, sensor lifetime, and adhesion for constructing an all-solid-state
      sensing device. In addition, effects of the diluent or plasticizer added in an
      epoxy resin/hardener system on the potentiometric behaviors are investigated. To
      demonstrate the practical analytical utility of the epoxy resin-based electrodes,
      chloride levels in various controls and biological specimens (e.g., human sera
      and whole blood) are determined with a flow-cell system.

PMID- 15253667
TI  - Open tubular immobilized metal ion affinity chromatography combined with MALDI MS
      and MS/MS for identification of protein phosphorylation sites.
AB  - Protein phosphorylation is one of the most important known posttranslational
      modifications. Tandem mass spectrometry has become an important tool for mapping
      out the phosphorylation sites. However, when a peptide generated from the
      enzymatic or chemical digestion of a phosphoprotein is highly phosphorylated or
      contains many potential phosphorylation residues, phosphorylation site assignment
      becomes difficult. Separation and enrichment of phosphopeptides from a digest
      mixture is desirable and often a critical step for MS/MS-based site
      determination. In this work, we present a novel open tubular immobilized metal
      ion affinity chromatography (OT-IMAC) method, which is found to be more effective
      and reproducible for phosphopeptide enrichment, compared to a commonly used
      commercial product, Ziptip from Millipore. A strategy based on a combination of
      OT-IMAC, sequential dual-enzyme digestion, and matrix-assisted laser
      desorption/ionization (MALDI) quadrupole time-of-flight tandem mass spectrometry
      for phosphoprotein characterization is presented. It is shown that MALDI MS/MS
      with collision-induced dissociation can be very effective in generating fragment
      ion spectra containing rich structural information, which enables the
      identification of phosphorylation sites even from highly phosphorylated peptides.
      The applicability of this method for real world applications is demonstrated in
      the characterization and identification of phosphorylation sites of a Na(+)/H(+)
      exchanger fusion protein, His182, which was phosphorylated in vitro using the
      kinase Erk2.

PMID- 15253668
TI  - Determination of origin of ephedrine used as precursor for illicit
      methamphetamine by carbon and nitrogen stable isotope ratio analysis.
AB  - The sale of ephedrine, one of the precursors of methamphetamine, is strictly
      controlled and monitored in various countries to prevent the production of
      illicit methamphetamine. There are three kinds of production scheme for ephedrine
      manufacture, and it is very useful for precursor control to investigate the
      origin of ephedrine used for the synthesis of illicit methamphetamine. By means
      of stable isotope ratio mass spectrometry (IR-MS), we investigated the origin of
      ephedrine based on the delta(13)C and delta(15)N values. The various origins of
      ephedrine (biosynthetic, semisynthetic, or synthetic) could be discriminated
      clearly by using these values. The delta(15)N values of synthetic ephedrine were
      more negative than those of ephedrine from other sources. By the repeated
      distillation of methylamine in our laboratory, we confirmed that this could be
      due to isotope separation during distillation for the purification of methylamine
      used for ephedrine synthesis. The values for ephedrine used as the precursor were
      well-correlated with those for methamphetamine synthesized from it. This drug
      characterization analysis should be useful to illuminate the origin of the
      precursors used for clandestine methamphetamine and to trace the diversion of
      medicinal ephedrine for illicit manufacture of methamphetamine.

PMID- 15253669
TI  - Development of a membrane-based immunofiltration assay for the detection of T-2
      toxin.
AB  - An improved analytical device capable of performing simultaneous immunofiltration
      based immunoassay on 30 samples in the presence of reference standards has been
      developed. The device consists of a rectangular membrane with 36 antibody spotted
      zones, one end of which was attached to a semirigid polyethylene card. A piece of
      wetted filter paper between the membrane and the polyethylene card absorbs the
      added reagent. The assay is a competitive one using T-2 toxin-horseradish
      peroxidase (T-2 toxin-HRP) as the labeled analyte and 4-chloro-1 naphthol (4CN)
      as the substrate. Signal amplification was done by the Super-CARD signal
      amplification method. Semiquantitative results were obtained by visual comparison
      of the color intensity of a sample spot with those of reference standards.
      Densitometric analysis was used for quantitation. The method allows rapid and
      easy determination of T-2 toxin in wheat and poultry feed with detection limits
      of 12.5 and 25 microg x kg(-)(1), respectively, with accuracy and precision.
      Matrix interference was eliminated by appropriate dilution of sample extracts
      with assay buffer. The detection sensitivity in ELISA was 10-fold higher than
      that in the membrane-based method. Noninfected samples were spiked with T-2 toxin
      at several concentrations and analyzed by the present method and rapid ELISA.
      Mean recoveries by both methods were between 80 and 108%. The correlation between
      the two methods was excellent (R(2) = 0.99).

PMID- 15253670
TI  - Nanospray mass spectrometry with indirect conductive graphite coating.
AB  - An easy and cost-effective method to manufacture a robust conductive graphite
      coating for nanospray mass spectrometry (nESI-MS) and capillary electrophoresis
      (CE)-nESI-MS is described. The method involves graphite coating of a tube sleeve,
      into which the nESI emitter is inserted and connected to a transfer capillary,
      instead of coating the actual emitter. The coating, made of graphite from a
      pencil and epoxy glue, was stable over long periods of use (>80 h) and showed
      excellent resistance toward various solvents. Stable electrospray was achieved in
      the investigated flow range (150-900 nL x min(-)(1)), and salbutamol,
      diphenhydramine, and nortriptyline (M(w): 239-263 g x mol(-)(1)) were detected in
      the nanomole per liter range during continuous pumping. CE-nESI-MS analysis gave
      excellent signal-to-noise ratios for 100-fmol injections. The technique allows
      simple exchange of the nESI emitter to suit a specific flow rate, and it
      minimizes risk of corona discharge.

PMID- 15253671
TI  - Characterization of polyacrylate membrane-coated fibers used in chemical
      absorption studies with programmed thermal treatment and FT-IR microscopy.
AB  - A polyacrylate (PA) film was coated onto a fused-silica fiber as a permeation
      membrane in a membrane-coated fiber (MCF) technique and a solid-phase
      microextraction technique. The molecular changes of the PA membrane after
      different temperature treatments were studied with FT-IR microscopy. The
      absorption bands of the PA aliphatic backbone at 2902, 2795, and 2740 cm(-)(1)
      remained unchanged over the elevated thermal treatments, indicating that the
      polymer backbone was stable over these conditions. The spectra of the PA membrane
      remained unchanged when the thermal treatment temperature was under 150 degrees
      C. When the temperature was 250 degrees C, the O-H stretching band in the -COOH
      groups of the poly(acrylic acid) at 3315 cm(-)(1) was significantly reduced. When
      the temperature was higher than 280 degrees C, this O-H band disappeared. These
      evidences suggested that the PA membrane underwent dehydroxyl reaction to form an
      anhydride when the thermal treatments were higher than 250 degrees C. Thermal
      treatments of a deuterated PA MCF confirmed the anhydride formation mechanism.
      The anhydride formation explained the absorption property of PA MCFs in GC
      applications where they must be preconditioned at 300 degrees C. The absorption
      data suggest that a PA fiber does not preferably absorb polar compounds (with
      permanent dipole moment); instead, it absorbs preferably aromatic compounds.

PMID- 15253672
TI  - Voltammetric peak separation of dopamine from uric acid in the presence of
      ascorbic acid at greater than ambient solution temperatures.
AB  - Peak overlap in voltammetry poses challenges for the quantitative analysis of
      electroactive species. Dopamine and uric acid are typically challenging to
      determine voltammetrically because of their very similar oxidation peak
      potentials. We report preliminary results of the use of a screen-printed carbon
      electrode for the determination of dopamine and uric acid in an electrolyte
      solution maintained above ambient temperatures. Higher temperatures resulted in
      dramatic shifting of the dopamine oxidation peak toward lower potentials, while
      the uric acid peak was essentially stationary. Ascorbic acid, an interference in
      voltammetric uric acid determinations, is effectively suppressed at higher
      temperatures. This resulted in a greater peak separation of dopamine from uric
      acid at higher temperatures, which is desirable for better peak integration. In
      addition, greater current responses for both species were recorded at higher
      temperatures. The cause for such an increase in peak current is unraveled using
      ac impedance measurements. Presented are preliminary results for determining
      dopamine and uric acid at temperatures higher than ambient. Much improved
      voltammetric peak separation and sensitivity is obtained at these higher
      temperatures compared to ambient.

PMID- 15253673
TI  - Enantiomer separations in capillary electrophoresis in the case of equal binding
      constants of the enantiomers with a chiral selector: commentary on the
      feasibility of the concept.
AB  - It is generally acknowledged that enantiomer separations in capillary
      electrophoresis are based on differences in the affinities of the analyte
      enantiomers toward the chiral selector expressed as equilibrium constants of the
      resulting temporary diastereomeric associates. However, as can be derived from
      theoretical considerations, a separation of enantiomers by CE is in principle
      also possible solely based on differences in the mobilities of the temporary
      diastereomeric complexes per se, when equal binding constants between analyte
      enantiomers and the chiral selector are assumed and observed.

PMID- 15253674
TI  - Bipolar disorder and cell membrane dysfunction. Progress toward integrative
      management.
AB  - Bipolar disorder (BD) is characterized by periods of abnormally elevated mood
      (mania) that cycle with abnormally lowered mood (depression). Multiple
      structural, metabolic, and biochemical abnormalities are evident in the brain's
      cortex, subcortex, and deeper regions. This disorder is highly genetically
      conditioned but also highly susceptible to environmental stressors: prenatal or
      perinatal insults, childhood sexual or physical abuse, challenging life events,
      substance abuse, and other toxic chemical exposures. Its high morbidity, lost
      productivity, and suicide risk place a great toll on society. Since World War II,
      BD has been steadily worsening with earlier age of onset, greater intensity of
      symptoms, and development of drug resistance. Incidence in children is rising and
      misdiagnosis is common. Disciplined management of the many risk factors is
      essential, including cognitive psychotherapy and support from family and
      community. Lithium has been the foundational treatment, followed by valproate and
      other mood stabilizers, antidepressants, and anticonvulsants. Several single
      nutrient and multinutrient supplements have also proven beneficial. Controlled,
      double-blind trials show multinutrient combinations of vitamins, minerals,
      orthomolecules, herbals, and the omega-3 fatty acids EPA and DHA to be effective
      monotherapy. The molecular action of lithium and valproate converge with
      nutrients on the level of the cell membrane and its molecular signal transduction
      systems. This emergent, unified rationale presages effective integrative
      management of bipolar disorder.

PMID- 15253675
TI  - Therapeutic applications of whey protein.
AB  - Whey, a protein complex derived from milk, is being touted as a functional food
      with a number of health benefits. The biological components of whey, including
      lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and
      immunoglobulins, demonstrate a range of immune-enhancing properties. In addition,
      whey has the ability to act as an antioxidant, antihypertensive, antitumor,
      hypolipidemic, antiviral, antibacterial, and chelating agent. The primary
      mechanism by which whey is thought to exert its effects is by intracellular
      conversion of the amino acid cysteine to glutathione, a potent intracellular
      antioxidant. A number of clinical trials have successfully been performed using
      whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease,
      osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited
      benefit in the arena of exercise performance and enhancement.

PMID- 15253676
TI  - Sub-laboratory hypothyroidism and the empirical use of Armour thyroid.
AB  - Evidence is presented that many people have hypothyroidism undetected by
      conventional laboratory thyroid-function tests, and cases are reported to support
      the empirical use of Armour thyroid. Clinical evaluation can identify individuals
      with sub-laboratory hypothyroidism who are likely to benefit from thyroid
      replacement therapy. In a significant proportion of cases, treatment with thyroid
      hormone has resulted in marked improvement in chronic symptoms that had failed to
      respond to a wide array of conventional and alternative treatments. In some
      cases, treatment with desiccated thyroid has produced better clinical results
      than levothyroxine. Research supporting the existence of sub-laboratory
      hypothyroidism is reviewed, and the author's clinical approach to the diagnosis
      and treatment of this condition is described.

PMID- 15253677
TI  - The causes of intestinal dysbiosis: a review.
AB  - Alterations in the bowel flora and its activities are now believed to be
      contributing factors to many chronic and degenerative diseases. Irritable bowel
      syndrome, inflammatory bowel disease, rheumatoid arthritis, and ankylosing
      spondylitis have all been linked to alterations in the intestinal microflora. The
      intestinal dysbiosis hypothesis suggests a number of factors associated with
      modern Western living have a detrimental impact on the microflora of the
      gastrointestinal tract. Factors such as antibiotics, psychological and physical
      stress, and certain dietary components have been found to contribute to
      intestinal dysbiosis. If these causes can be eliminated or at least attenuated
      then treatments aimed at manipulating the microflora may be more successful

PMID- 15253678
TI  - Evaluating the clinical relevance of food sensitivity tests: a single subject
      experiment.
AB  - A number of tests are available to identify food sensitivities. This article
      presents an analysis of the diagnostic value of nine different food sensitivity
      tests run concurrently on a healthy 33-year-old female with a previous diagnosis
      of environmental allergies. This case study evaluated conventional allergy tests
      (skin prick and serum IgE), tests of other immune-mediated reactions (serum IgG
      and salivary IgA), and tests that claim to measure the energetic reaction of the
      whole person to particular foods (kinesiology, Vega, and Carroll testing). The
      results of an elimination/challenge test were used as indicators of true food
      reactions in order to calculate the sensitivity, specificity, and positive
      predictive value (PPV) of each test. In a separate evaluation, the variability of
      results across the four tests measuring IgG was determined. Results show several
      tests (one of the two serum tests of IgG alone, both serum tests of IgE and IgG,
      skin prick testing, and Carroll testing) may have very high (100 percent)
      specificity and PPV when test results are compared to the results of an
      elimination/challenge test. Sensitivity, however, is low across tests (50-60
      percent), likely because different tests measure different mechanisms of food
      reactions and because food sensitivities can be the result of a number of
      different mechanisms. Very little consistency was found among the results of the
      four tests measuring IgG - 79-83 percent disagreement. This study shows a number
      of tests may be useful in identifying foods to which a patient is reactive;
      however, no one test is likely to identify all reactive foods.

PMID- 15253679
TI  - Monograph. Monascus purpureus (red yeast rice).

PMID- 15253680
TI  - Monograph. Withania somnifera.

PMID- 15253681
TI  - Chronic obstructive pulmonary disease overview: prevalence, pathogenesis, and
      treatment.
AB  - OBJECTIVE: To discuss the current clinical data on the prevalence, pathogenesis,
      staging, and treatment of chronic obstructive pulmonary disease (COPD). DATA
      SOURCES: This article reviews the results of published studies and presents data
      from current guidelines and expert opinion. CONCLUSIONS: An insidious disorder
      that is asymptomatic early, COPD (the preferred term for patients with chronic
      bronchitis and emphysema) prevalence has increased in recent decades, adding a
      significant burden to patients and the health care system. COPD, an inflammatory
      disorder secondary to the chronic inhalation of principally tobacco smoke,
      induces a progressive deterioration in pulmonary function with a marked increase
      in morbidity and mortality over time. The signs and symptoms of COPD, which
      appear in many patients only after forced expiratory volume in 1 second (FEV1) is
      <50% predicted, should not be confused with asthma, because these two diseases
      display grossly different inflammatory processes, etiologies, clinical courses,
      responses to treatment, and outcomes. The effective management of COPD relies
      primarily on early identification, changing smoking habits, and the use of
      bronchodilators to improve pulmonary function, symptoms, acute exacerbation rate,
      quality of life, mortality, and comorbidities. With early detection and
      aggressive treatment, the natural history of this disease can be improved. Office
      spirometry for all smokers and ex-smokers as well as those with respiratory
      symptoms is mandatory as a means of achieving early diagnosis and improving long
      term outcomes.

PMID- 15253682
TI  - Chronic obstructive pulmonary disease treatment options.
AB  - OBJECTIVE: To discuss current therapies for the treatment of chronic obstructive
      pulmonary disease (COPD) and their efficacy and use according to current
      treatment guidelines. SUMMARY: The overall approach to the management of stable
      COPD is a stepwise increase in treatment, depending on disease severity. Inhaled
      bronchodilators are the cornerstone of symptomatic management of COPD and include
      beta 2-agonists, anticholinergics, and methylxanthines. Short-acting beta 2
      agonist bronchodilators (e.g., albuterol) have a quick onset of action and are
      useful for rescue. Long-acting bronchodilators are taken on a regular basis to
      prevent or reduce symptoms and include beta 2-agonists saleterol and formoterol
      and anticholinergics ipratropium bromide and tiotropium bromide. Methylxanthines
      have decreased in usage due to potential toxicity. The Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) guidelines are an international
      initiative, updated in 2003. GOLD staging consists of 5 levels of severity;
      treatment guidelines recommend a step-wise approach, with short- and long-acting
      bronchodilators as the cornerstone of therapy. CONCLUSION: Appropriate
      pharmacologic treatment of symptomatic COPD can result in reduced patient
      limitations and health care utilization and improved health-related quality of
      life.

PMID- 15253683
TI  - Assessing the need for a clinical COPD care program in a managed care
      organization.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD), a systemic inflammatory
      condition, is costly and often devastating to patient quality of life. COPD is
      also greatly underdiagnosed and often inappropriately treated. A managed care
      organization therefore evaluated whether a systemwide COPD clinical program
      within its organization may be appropriate. The organization examined the current
      prevalence, costs, and adherence to clinical treatment guidelines. OBJECTIVE: To
      identify the prevalence and costs of COPD within the managed care organization
      and to ascertain whether the condition could be better managed using a systemwide
      clinical program. CONCLUSION: Both diagnosis and treatment of COPD would likely
      be improved with a comprehensive clinical COPD care program that would include
      measuring outcomes, stratifying COPD patients by risk, and initiating disease
      state management efforts.

PMID- 15253684
TI  - The importance of early diagnosis of multiple sclerosis.
AB  - OBJECTIVE: To describe the current understanding of the diagnosis and treatment
      of multiple sclerosis (MS) and to explore the use of magnetic resonance imaging
      (MRI) assessment as a prognostic tool and an indicator in the diagnosis of MS.
      SUMMARY: MS is a chronic, progressive, demyelinating disease of the central
      nervous system that is associated with a significant economic burden. At this
      time, immunomodulatory agents (interferon beta-1a (IFNbeta-1a) [Avonex], IFNbeta
      1a [Rebif], IFNbeta-1b [Betaseron], and glatiramer acetate [Copaxone]) are first
      line agents, which are reported to reduce relapse rates. The diagnostic criteria
      for MS have evolved over time to include MRI findings as an integral part of the
      diagnosis. However, the most recent criteria (McDonald) are focused on the
      diagnosis of definite MS and do not address the status of patients with a first
      demyelinating event (clinically isolated syndrome [CIS]). This is an important
      issue because a CIS is highly predictive of developing further inflammation and
      definite MS when the episode occurs in conjunction with lesions on the initial
      MRI. Many times, MRI findings do not correlate with clinical symptoms, and
      clinically silent lesions are identified. Therefore, the use of MRI is salient to
      the early diagnosis of high-risk patients. The evolution of thought concerning
      early treatment in MS is based on an increased understanding of the pathology of
      the disease. Axonal loss occurs early in the disease process, and both white
      matter and gray matter are affected. Studies that have analyzed early treatment
      in patients highly likely to have MS (clinically isolated events with evidence of
      lesions on MRI) report significant benefits in delaying further changes on MRI
      and further attacks. Patients who begin treatment later do not reap the same
      benefits as those who begin treatment earlier during the disease course.
      CONCLUSION: Patients with clinically isolated events should be referred promptly
      to a neurologist for assessment, including MRI scans. An early recognition of the
      inflammatory process enables patients to begin treatment with an immunomodulatory
      agent even before the technical diagnosis of definite MS so that the degenerative
      progression of MS can be retarded.

PMID- 15253685
TI  - Neutralizing antibodies to multiple sclerosis treatments.
AB  - OBJECTIVE: This article reviews the incidence and clinical significance of
      neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS)
      undergoing treatment with interferon beta (IFNbeta). Implications for practice
      are also discussed in light of the currently available data on the clinical
      consequences of NAbs in patients with MS. SUMMARY: As with other recombinant
      protein drugs used for the treatment of a number of diseases, antibodies commonly
      develop to IFNbeta products during the treatment of patients with MS.
      Neutralizing antibodies (NAbs) are a subset of antibodies that reduce or diminish
      the biologic activity of IFNbeta. Three formulations of IFNbeta are currently
      available for the treatment of relapsing-remitting MS: IFNbeta-1b (Betaseron),
      intramuscular (i.m.) IFNbeta-1a (Avonex), and subcutaneous (s.c.) IFNbeta-1a
      (Rebif). Individual phase III clinical trials and direct comparison studies have
      shown that NAbs develop more frequently during treatment with IFNbeta-1b than
      IFNbeta-1a and that between the 2 IFNbeta-1a products, NAbs develop more
      frequently during treatment with s.c. IFNbeta-1a than IM IFNbeta-1a. Data from
      clinical trials of IFNbeta products indicate that clinical efficacy of IFNbeta is
      reduced in NAb-positive patients. CONCLUSION: In light of these data, the
      immunogenicity of IFNbeta products should be considered prior to initiating
      treatment with IFNbeta. Also, ongoing laboratory monitoring of patients treated
      with higher-dose IFNbeta is recommended for early detection of NAbs.

PMID- 15253686
TI  - Clinical management of multiple sclerosis: the treatment paradigm and issues of
      patient management.
AB  - OBJECTIVE: To summarize the conclusions of an expert panel of neurologists
      specializing in multiple sclerosis (MS) convened for the purpose of creating a
      treatment algorithm with regard to the clinical management of MS. The panel was
      sponsored by the Health Science Center for Continuing Medical Education and the
      University of Medicine and Dentistry of New Jersey and supported by an
      educational grant from Biogen Idec, Inc. SUMMARY: MS is a chronic demyelinating
      disease characterized by a variable clinical course. Currently, there is no cure
      for MS, and the management of MS requires lifelong treatment with disease
      modifying agents. Some patients respond well to therapy for many years, whereas
      others may have aggressive disease that is more difficult to manage. Hence, given
      the variable nature in the course of MS and patients. response to treatment,
      neurologists must individualize care for their patients. An MS treatment
      algorithm was recently developed by a panel of neurologists who are MS experts to
      provide community neurologists with best-practice protocols for treating and
      managing their MS patients. The panel of experts categorized MS into 3 different
      stages, with patients transitioning between the stages based on their response to
      therapy and disease progression. Stage I represents MS early in the progression
      of the disease, during which platform drug therapy is recommended (i.e.,
      interferon beta-1b [IFNbeta-1b], IFNbeta-1a, or glatiramer acetate). The results
      of randomized, controlled clinical trials suggest that IFNbeta is the optimal
      choice for platform therapy. Despite treatment with platform therapy, it is
      common for patients to experience some ongoing symptoms and periodic
      exacerbations of the disease (annual relapse rate of 0.59 to 0.84 on treatment);
      such relapses should not be considered treatment failures and are best managed
      with steroids. Stage II represents acute breakthrough disease (i.e., when the
      clinical activity becomes more frequent or severe). This stage is best managed by
      the addition of pulse corticosteroids to the platform drug. Stage III represents
      continued breakthrough disease and is best managed by the addition of
      immunosuppressants to the platform drug. CONCLUSION: The MS treatment algorithm
      provides an educational resource for physicians. It should assist all health care
      professionals involved in the management of MS patients and enhance their ability
      to improve quality of life for these patients over the course of the disease.

PMID- 15253687
TI  - Stepped-care approach to treating MS: a managed care treatment algorithm.
AB  - OBJECTIVE: To introduce a model treatment algorithm for use in the managed care
      setting as a strategy to provide ongoing disease management and long-term care
      for patients with multiple sclerosis (MS), with the goal of delaying disease
      progression and the associated disability and cognitive dysfunction. SUMMARY: MS
      is a chronic inflammatory disorder of the central nervous system that is
      associated with progressive disability and cognitive dysfunction. Currently,
      management of MS involves planning an effective long-term treatment strategy that
      can delay the progression of the disease. This article reviews a typical stepped
      care approach to treating MS that is based on the concept of a platform drug,
      which is an agent that provides baseline immunomodulatory action throughout the
      course of the disease. Considerations for selecting a platform therapy include
      the effect on the full spectrum of MS (disability, relapses, lesion load, and
      atrophy as well as patient compliance and the potential impact of neutralizing
      antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing
      MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these,
      the IFNbetas are generally recommended as platform therapy because all have shown
      significant effects on relapses, magnetic resonance imaging parameters of the
      disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous
      (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained
      disability. Patients being treated with IFNbetas can develop NAbs to the drug,
      which can lead to a loss of efficacy and subsequent occurrence of breakthrough
      disease. The 3 different formulations of IFNbeta are associated with a varying
      incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b
      [Betaseron], 45%). Antibodies also form against glatiramer acetate, although
      their clinical significance needs to be elucidated. As the disease progresses or
      has periods of aggressive activity, the stepped-care approach is to add other
      agents onto the platform therapy to improve control of the disease. CONCLUSION:
      Stepped care, as outlined in this model treatment algorithm for the managed care
      setting, is an effective method to achieve the fundamental goal of MS treatment,
      that is, to delay disease progression and the associated disability and cognitive
      impairment.

PMID- 15253688
TI  - Clinical update on alefacept: consideration for use in patients with psoriasis.
AB  - OBJECTIVE: Alefacept was the first of the biologic agents to be approved for the
      treatment of adult patients with moderate-to-severe chronic plaque psoriasis who
      are candidates for systemic therapy or phototherapy. This fully human fusion
      protein inhibits the activation of and reduces levels of memory (CD45RO+) T
      cells, a subpopulation of lymphocytes that plays a critical role in the
      pathogenesis of psoriasis. The purpose of this article is to provide a clinical
      update on the use of this agent in patients with psoriasis. SUMMARY: A single
      course of alefacept, defined as 12 weekly injections followed by 12 treatment
      free weeks, provides clinically meaningful improvements in the symptoms of
      psoriasis for a majority of patients. Patients who achieved a response have been
      shown to maintain the benefit for a median duration of about 7 months, without
      the need for systemic therapy or phototherapy. With each additional course of
      alefacept, the percentage of patients responding increases, confirming the
      incremental benefit of repeated administration. More than 1,300 patients have
      received alefacept in controlled clinical trials. Over multiple courses of
      therapy, alefacept-induced reductions in circulating lymphocyte counts were
      consistent and not cumulative. The incidences of serious adverse events,
      discontinuations, malignancies, and antialefacept antibodies were low and did not
      increase with subsequent courses. No relationship was observed between decreases
      in lymphocyte counts and incidences of infections or malignancies. No cases of
      opportunistic infections, including tuberculosis, have been reported. The
      favorable safety profile of alefacept was maintained in patients who received
      concomitant or prior immunosuppressants. Alefacept did not cause reactivation of
      tuberculosis in case studies of patients who showed a purified protein derivative
      reaction prior to the initiation of therapy. Immune responses to a neoantigen and
      recall antigen remained intact in alefacept-treated patients, suggesting that
      vaccinations may be possible during therapy. CONCLUSION: Alefacept is an
      effective intermittent therapy for psoriasis that can provide extended treatment
      free and disease-free periods, which may lessen the need for treatment over time.
      The incremental efficacy seen with each subsequent course of alefacept suggests
      that physicians should administer 2 courses to determine efficacy before altering
      therapeutic interventions. The selective mechanism of action of alefacept affords
      multiple safety advantages and no apparent increased risk of infections or
      malignancies.

PMID- 15253689
TI  - Considerations for assessing the cost of biologic agents in the treatment of
      psoriasis.
AB  - OBJECTIVE: This paper will establish the rationale for developing a long-term
      cost model to assess the utilization and associated economics of biologic agents
      in the treatment of moderate-to-severe psoriasis. This information should assist
      with defining the total cost of drug treatment when using biologic therapy to
      treat psoriasis. SUMMARY: The development of biologic therapies has effected the
      treatment of many chronic diseases, including psoriasis. Managed care
      organizations are debating the appropriate use of these injectable drugs because
      of the associated acquisition costs and administration requirements. Important
      considerations for evaluating these agents include the ability to produce off
      treatment remissions, the ability to improve patients. quality of life, and
      safety and tolerability profiles. A remittive therapy may be a good early
      treatment for these patients because it offers the chance to avoid lifelong
      therapy. In addition, the safety and tolerability profiles of all biologic agents
      are substantially improved compared with conventional systemic psoriasis
      treatments. However, therapy must be individualized because risks vary with each
      agent. Thus, these differences in the biologic agents should be considered in the
      assessment of the economic impact and drug utilization of biologics for patients
      with psoriasis. CONCLUSION: The biologic agents currently used in the treatment
      of psoriasis offer patients new hope for safe and effective therapy. Comparison
      of these agents by managed care decision makers requires consideration of
      characteristics that differentiate the agents, including efficacy, duration of
      off-treatment response, and safety and tolerability.

PMID- 15253690
TI  - Skeletal muscle morphology and capillarization of renal failure patients
      receiving different dialysis therapies.
AB  - The morphology of gastrocnemius muscles was examined in RFPs (renal failure
      patients) being treated using HD (haemodialysis) and CAPD (continuous ambulatory
      peritoneal dialysis). RFPs (n=24) volunteered to participate in the present
      study. Twelve RFPs (five women and seven men; mean age, 55 years) were undergoing
      CAPD treatment and 12 RFPs (two women and ten men; mean age, 62 years) were
      undergoing HD treatment. Muscle biopsies from gastrocnemius muscles were found
      not to differ (P>0.05) in fibre type distribution, MyHC (myosin heavy chain)
      expression or fibre CSA (cross-sectional area) between the two groups. There
      were, however, significant differences (P<0.05) in CC/F (capillary
      contact/fibre), C/F (capillary to fibre ratio) and cytochrome c oxidase activity.
      The HD group had 33% more CC/F, with a 19% higher C/F and 33% greater cytochrome
      c activity in glycolytic fibres (II) than the CAPD group. There were no apparent
      differences in age, gender, co-morbidity, self-reported physical activity or
      physical functioning between the two groups, which could account for the
      difference in muscle capillarity between the groups. The HD patients were,
      however, administered heparin as a routine part of the dialysis therapy. The
      possibility is discussed that heparin in combination with mild anaemia and
      acidosis may have augmented angiogenesis in the HD patients.

PMID- 15253691
TI  - Forced expression of the cyclin B1-CDC2 complex induces proliferation in adult
      rat cardiomyocytes.
AB  - Repair of the mature mammalian myocardium following injury is impaired by the
      inability of the majority of cardiomyocytes to undergo cell division. We show
      that overexpression of the cyclin B1-CDC2 (cell division cycle 2 kinase) complex
      re-initiates cell division in adult cardiomyocytes. Thus strategies targeting the
      cyclin B1-CDC2 complex might re-initiate cell division in mature cardiomyocytes
      in vivo and facilitate myocardial regeneration following injury.

PMID- 15253693
TI  - Ischemic acute renal failure: an inflammatory disease?
AB  - Inflammation plays a major role in the pathophysiology of acute renal failure
      resulting from ischemia. In this review, we discuss the contribution of
      endothelial and epithelial cells and leukocytes to this inflammatory response.
      The roles of cytokines/chemokines in the injury and recovery phase are reviewed.
      The ability of the mouse kidney to be protected by prior exposure to ischemia or
      urinary tract obstruction is discussed as a potential model to emulate as we
      search for pharmacologic agents that will serve to protect the kidney against
      injury. Understanding the inflammatory response prevalent in ischemic kidney
      injury will facilitate identification of molecular targets for therapeutic
      intervention.

PMID- 15253694
TI  - Inflammatory cells in ischemic acute renal failure.
AB  - Ischemic acute renal failure (ARF) is increasingly recognized as involving a
      complex cascade of mechanisms with both acute and chronic consequences. Attention
      to nontraditional mediators of ARF such as inflammatory pathways and
      microvascular events has yielded new paradigms and avenues of research. The
      initiation phase of renal ischemia/reperfusion (I/R) injury damage involves
      microvascular hemodynamic changes characterized by red blood cell sludging with
      platelets and leukocytes. Blocking leukocyte-endothelial interactions has yielded
      significant protection from renal I/R injury in experimental models. However,
      experiments focusing on the role of the neutrophil have led to a modest
      expectation of its role in ARF. Recent studies have found that T cells directly
      mediate renal injury in experimental I/R injury. The CD4+ T cell, working both
      via interferon-gamma (IFN-gamma) and costimulatory molecules appears to be an
      important modulator of ARF. The B cell has recently been implicated in ARF.
      Little is known about the role for the macrophage. Finally, resident kidney cells
      likely contribute to the inflammatory pathogenesis of I/R damage and
      protection/repair, but how, and to what extent they are involved is not known.
      New tools to modulate inflammatory cells, particularly mononuclear leukocytes,
      hold promise for clinical trials in ARF.

PMID- 15253695
TI  - T cells as mediators in renal ischemia/reperfusion injury.
AB  - Inflammation has been established to contribute substantially to the pathogenesis
      of ischemia/reperfusion (I/R) with a central role for particular cells, adhesion
      molecules, and cytokines. Until recently, most of the research trying to unravel
      the pathogenesis of I/R injury has been focused on the role of neutrophils.
      However, recent studies have brought evidence that T cells and macrophages are
      also important leukocyte mediators of renal and extrarenal (liver) I/R injury. In
      vivo depletion of CD4+ cells but not CD8+ cells in wild-type mice was protective
      in I/R of the kidney. A marked preservation of liver function was also found
      after I/R in T-cell deficient athymic mice. Blocking the b130/CD28 costimulatory
      pathway by CTLA-4 Ig (recombinant fusion protein) ameliorated renal dysfunction
      and decreased mononuclear cell infiltration in I/R of the kidney. b130-1
      expression was found limited to the membrane of the endothelial cells of the
      ascending vasa recta, resulting in trapping of CD28-expressing CD4 T cells. This
      trapping of leukocytes results in the upstream congestion in the ascending
      arterial vasa recta, generating the since more than 150 years described medullary
      vascular congestion of the kidney soon after ischemic injury. It seems worthwhile
      to study a combination therapy using anti-inflammatory/anti-adhesion molecules in
      the early phase of I/R.

PMID- 15253696
TI  - Endothelial injury and dysfunction: role in the extension phase of acute renal
      failure.
AB  - The pathophysiology of ischemic acute renal failure (ARF) involves a complex
      interplay between renal hemodynamics, tubular and endothelial cell injury, and
      inflammatory processes. A growing body of evidence supports the contribution of
      altered renal vascular function, especially at the microvascular level, in
      initiating and subsequently extending the initial tubular injury. The extension
      phase of ischemic ARF involves continued reduction in renal perfusion, ongoing
      hypoxia, and inflammatory processes that occur during reperfusion and contribute
      to continued tubular cell injury. Vascular endothelial cell injury and
      dysfunction play a vital part in this extension phase. With injury, the
      endothelial cell loses its ability to regulate vascular tone, perfusion,
      permeability and inflammation/adhesion. This loss of regulatory function has a
      detrimental impact upon renal function. Vascular congestion, edema formation,
      diminished blood flow, and infiltration of inflammatory cells have been
      documented in the corticomedullary junction of the kidney. However, linking their
      genesis to microvascular endothelial injury and dysfunction has been difficult.
      New diagnostic and therapeutic approaches to ischemic ARF must incorporate these
      finding to devise early recognition strategies and therapeutic approaches.

PMID- 15253697
TI  - Apoptotic pathways in ischemic acute renal failure.
AB  - The study of cell death has emerged as an important and exciting area of research
      in cell biology. Although two kinds of cell death, apoptosis and necrosis, are
      recognized, one of the major advances in our understanding of cell death has been
      the recognition that the pathways traditionally associated with apoptosis may be
      very critical in the form of cell injury associated with necrosis. Renal tubular
      epithelial cell injury from ischemia has been generally regarded as a result of
      necrotic form of cell death. We briefly describe recent evidence indicating that
      pathways generally associated with apoptosis, including endonuclease activation,
      role of mitochondria and caspases, are important in renal tubular injury. It is
      likely that the cascades that lead to apoptotic or necrotic mode of cell death
      are activated almost simultaneously and may share some common pathways.

PMID- 15253698
TI  - Apoptosis in ischemic renal injury: roles of GTP depletion and p53.
AB  - Apoptosis is increasingly recognized as a major mode of cell demise after
      ischemic injury to the kidney. The mediators of apoptotic cell death are many and
      include changes in intracellular pH, calcium, free radicals, ceramide, and
      adenosine triphosphate (ATP) depletion. Recently, we identified guanosine
      triphosphate (GTP) depletion as an independent trigger for apoptotic death after
      chemical anoxia in vitro. We further demonstrated that GTP salvage with guanosine
      inhibits tubular cell apoptosis after ischemic injury in vivo. This inhibition of
      apoptosis was accompanied by a significant protective effect on renal function.
      We also showed that p53 is the mediator of apoptosis in the setting of GTP
      depletion and ischemic injury. Indeed, salvage of GTP with guanosine prevented
      the ischemia-induced increase in p53 protein. Further, pifithrin-alpha, a potent
      and specific inhibitor of p53, inhibited apoptosis and protected renal function
      with a profile similar to that seen with guanosine. Finally, the protective
      effects of pifithrin-alpha involved both down-regulation of the transcriptional
      activation of Bax and a direct inhibition of p53 translocation to mitochondria.
      We propose that GTP depletion and activation of p53 are major inducers of
      apoptotic cell death after ischemic renal injury. In this setting, guanosine and
      pifithrin-alpha are potent inhibitors of apoptosis and are thus potentially
      useful in preventing and ameliorating functional injury to the ischemic kidney.

PMID- 15253699
TI  - Cell cycle regulation: repair and regeneration in acute renal failure.
AB  - Research into mechanisms of acute renal failure has begun to reveal molecular
      targets for possible therapeutic intervention. Much useful knowledge into the
      causes and prevention of this syndrome has been gained by the study of animal
      models. Most recently, investigation of the effects on acute renal failure of
      selected gene knock-outs in mice has contributed to our recognition of many
      previously unappreciated molecular pathways. Particularly, experiments have
      revealed the protective nature of two highly induced genes whose functions are to
      inhibit and control the cell cycle after acute renal failure. By use of these
      models we have started to understand the role of increased cell cycle activity
      after renal stress, and the role of proteins induced by these stresses that limit
      this proliferation.

PMID- 15253700
TI  - The role of mitochondria in ischemia/reperfusion injury in organ transplantation.
AB  - In organ transplantation, ischemia/reperfusion (I/R) results in damage that may
      affect cell viability and lead to organ failure. I/R injury involves a complex
      cascade of events, including loss of energy, derangement of the ionic hemostasis,
      production of reactive oxygen species, and cell death. In this context,
      mitochondria may be critical organelles, since they undergo major changes that
      may contribute to the injury occurring during I/R.

PMID- 15253701
TI  - Progenitor cells in the kidney: biology and therapeutic perspectives.
AB  - The stem cell may be viewed as an engineer who can read the blue print and become
      the building. The role of this fascinating cell in physiology and pathophysiology
      has recently attracted a great deal of interest. The archetype of stem cells is
      the zygote: one cell capable of endless proliferation and differentiation into
      all tissue types in the human body. Historically, the differentiation of
      embryonic stem cells is seen as an irreversible process with restricting
      possibilities for differentiation leading finally to a terminally differentiated
      cell type. Stem cells have also been described in the adult. They were first
      defined in tissues with a high cell turnover like skin and gut. Today, stem cells
      have also been shown in tissues with no or low regenerative potential and
      turnover, like the kidney. Traditionally, adult stem cells were thought to be
      restricted in their differentiative and regenerative potential to the tissues in
      which they reside. However, the stem cell concept is changing rapidly as evidence
      is mounting that adult stem cells not only reside locally in specific niches, but
      may also be recruited from the circulation to actively participate in the
      regeneration of various tissues. Furthermore, reverse differentiation has been
      demonstrated. This means that highly specialized cell types are able to
      dedifferentiate and engage in stem cell like activities. Moreover,
      transdifferentiation of mature cells into different cell types has been reported.
      This paper will review our current knowledge on renal stem cells and progenitor
      cells. Specifically, it will discuss the role of progenitor cells and
      transdifferentiation in renal repair and maintenance. Finally, the potential
      clinical implications of these findings will be discussed.

PMID- 15253702
TI  - Long-term effects of acute ischemia and reperfusion injury.
AB  - Ischemia reperfusion (I/R) injury plays a major role in delayed graft function
      and long-term changes after kidney transplantation. By using different
      therapeutic strategies to prevent I/R injury in rat models of kidney
      transplantation we studied relationships between inflammatory cell arrival and
      adhesion molecule expression. In other rat models for acute renal failure we
      investigated the effect of up-regulation of protective genes such as heme
      oxygenase-1 (HO-1) on infiltrating cells, showing that infiltrating cells also
      contribute to beneficial effects. In order to gain more insight into the complex
      mechanisms of long-term changes after kidney transplantation, we started a
      protocol biopsy program to study histologic changes 6, 12, and 26 weeks after
      transplantation. The following article clarifies some of the complex mechanisms
      contributing to long-term changes caused by I/R injury.

PMID- 15253703
TI  - Regulation of intestinal epithelial gene expression in hypoxia.
AB  - Mucosal hypoxia is intimately associated with chronic inflammation in the
      gastrointestinal tract in disease such as Crohn's disease. Under such conditions,
      intestinal epithelial cells may become a source of proinflammatory cytokines,
      including tumor necrosis factor alpha (TNFalpha), which actively contribute to
      ongoing inflammation through autocrine disruption of epithelial barrier function.
      These events are critically dependent upon alterations in the expression and
      function of the cAMF response element binding protein (CREB). Here we review our
      understanding of the molecular mechanisms underlying the regulation of CREB
      activity in intestinal epithelial cells in hypoxia.

PMID- 15253704
TI  - Antiretroviral and immunosuppressive drug-drug interactions: an update.
AB  - With the introduction of highly active antiretroviral therapy (HAART), human
      immunodeficiency virus (HIV) infection has become a chronic disease with more
      frequent end-stage organ failures. As a result, the question of transplantation
      in HIV patients is raised more often. However, some of the HAART regimen
      medications require elimination or metabolism via the P-glycoprotein (P-gp) and
      multidrug-resistant protein (MRP) transporters or via the cytochrome P450 enzyme
      system. Since these transporters and enzymes are also responsible for the
      clearance of immunosuppressive drugs, drug-drug interactions are likely to occur.
      Indeed, profound drug-drug interactions between protease inhibitors and
      immunosuppressive drugs have been observed and they required reductions in drug
      dosage. In contrast, HAART using nucleoside or nonnucleoside reverse
      transcriptase inhibitors without the use of protease inhibitors has been shown to
      produce less significant drug-drug interactions. It is thus crucial to take into
      account those potential pharmacokinetic and/or pharmacodynamic drug-drug
      interactions in order to avoid drug toxicity or a lack of efficacy. The aim of
      this work was to review and synthesize the international literature on this field
      in order to give practical recommendations on how to manage immunosuppressive
      drugs in HIV patients who get transplanted and on how to handle HAART therapy in
      transplant-recipient patients who get infected with HIV.

PMID- 15253705
TI  - Multiple facets of macrophages in renal injury.
AB  - Macrophage infiltration is a common feature of renal disease and their presence
      has been synonymous with tissue damage and progressive renal failure. More
      recently work has focused on the heterogeneity of macrophage activation and in
      particular their ability to curtail inflammation and restore normal function.
      This has led to the view that it is macrophage function rather than their number
      that is important in determining the outcome of inflammatory disease. This review
      will focus on the pathways that regulate macrophage infiltration and activation
      and how these could be manipulated to control renal inflammatory disease. In
      particular, the ability of specific cell surface receptors and intracellular
      signaling pathways to control macrophage activation and how macrophages can be
      genetically manipulated to develop properties that favor resolution over ongoing
      injury.

PMID- 15253706
TI  - Homozygosity for uromodulin disorders: FJHN and MCKD-type 2.
AB  - BACKGROUND: Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) and
      familial juvenile hyperuricemic nephropathy (FJHN) are heritable renal diseases
      with autosomal-dominant transmission and shared features, including polyuria,
      progressive renal failure, and abnormal urate handling, which leads to
      hyperuricemia and gout. Mutations of the UMOD gene, disrupting the tertiary
      structure of uromodulin, cause MCKD2 and FJHN. METHODS: Haplotype analysis of a
      large Spanish family with MCKD was carried out to determinate genetic linkage to
      MCKD2 locus. Mutation detection was performed by direct sequencing of the UMOD
      gene. The level of Tamm-Horsfall protein in the urine was measured by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot
      analysis. RESULTS: Linkage to MCKD2 locus was demonstrated (LOD score: 4.13), and
      a known pathogenic uromodulin mutation was found in exon 4, corresponding to
      Cys255Tyr, disrupting the light chain binding domain of the protein. In this
      consanguineous family there were three patients homozygous for the C255Y
      mutation, and multiple heterozygous cases, allowing the MCKD phenotypes
      associated with one or two mutant alleles to be compared. The homozygous
      individuals survived to adulthood, although presenting an earlier onset of
      hyperuricemia and faster progression to end-stage renal disease than heterozygous
      individuals. Western analysis revealed lower levels of urine THP in one
      heterozygous patient compared with a normal control patient, both with normal
      renal function. CONCLUSION: The study shows that individuals with two UMOD
      mutations are viable, but they do have more severe disease on average than
      heterozygotes. This family sheds light on the possible disease mechanism in this
      disorder.

PMID- 15253707
TI  - Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant
      and steroid-sensitive nephrotic syndrome.
AB  - BACKGROUND: Nephrotic syndrome (NS) represents the association of proteinuria,
      hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant nephrotic syndrome
      (SRNS) is defined by primary resistance to standard steroid therapy. It remains
      one of the most intractable causes for end-stage renal disease (ESRD) in the
      first two decades of life. Sporadic mutations in the Wilms' tumor suppressor gene
      WT1 have been found to be present in patients with SRNS in association with
      Wilms' tumor (WT) and urinary or genital malformations, as well as in patients
      with isolated SRNS. METHODS: To further evaluate the incidence of WT1 mutations
      in patients with NS we performed mutational analysis in 115 sporadic cases of
      SRNS and in 110 sporadic cases of steroid-sensitive nephrotic syndrome (SSNS) as
      a control group. Sixty out of 115 (52%) patients with sporadic SRNS were male,
      55/115 (48%) were female. Sex genotype was verified by haplotype analysis.
      Mutational analysis was performed by direct sequencing and by denaturing high
      performance liquid chromatography (DHPLC). RESULTS: Mutations in WT1 were found
      in 3/60 (5%) male (sex genotype) cases and 5/55 (9%) female (sex genotype) cases
      of sporadic SRNS, and 0/110 (0%) sporadic cases of SSNS. One out of five female
      patients with mutations in WT1 developed a WT, 2/3 male patients presented with
      the association of urinary and genital malformations, 1/3 male patients presented
      with sexual reversal (female phenotype) and bilateral gonadoblastoma, and 4/5
      female patients presented with isolated SRNS. CONCLUSION: According to the data
      acquired in this study, patients presenting with a female phenotype and SRNS and
      male patients presenting with genital abnormalities should especially be screened
      to take advantage of the important genetic information on potential Wilms' tumor
      risk and differential therapy. This will also help to provide more data on the
      phenotype/genotype correlation in this patient population.

PMID- 15253708
TI  - NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant
      nephrotic syndrome and low post-transplant recurrence.
AB  - BACKGROUND: Mutations of NPHS2 are causative in familial autosomal-recessive (AR)
      and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to
      determine the spectrum of NPHS2 mutations and to establish genotype-phenotype
      correlations. METHODS: NPHS2 mutation analysis was performed in 338 patients from
      272 families with SRNS: 81 families with AR SRNS, 172 patients with sporadic
      SRNS, and 19 patients with diffuse mesangial sclerosis (DMS). RESULTS: Twenty-six
      different pathogenic NPHS2 mutations were detected, including 13 novel mutations.
      The mutation detection rate was 43% for familial AR and 10.5% for sporadic SRNS,
      confirming genetic heterogeneity. No pathogenic NPHS2 mutations were found in DMS
      patients. Age at onset in patients with two pathogenic mutations was earlier,
      especially in cases with frameshift, truncating, and the R138Q missense
      mutations. Patients with only one NPHS2 mutation or variant had late-onset NS.
      Triallelic inheritance was observed in one patient with a homozygous R138Q
      mutation and a de novo NPHS1 mutation. Among 32 patients with two NPHS2 mutations
      who underwent kidney transplantation, only one developed late recurrence of focal
      segmental glomerulosclerosis (FSGS). Among 25 patients with sporadic SRNS and
      post-transplantation recurrence, we detected a heterozygous NPHS2 mutation in one
      case, and heterozygous variants/polymorphisms in 3 cases. CONCLUSION: Patients
      with two pathogenic NPHS2 mutations present with early-onset SRNS and very low
      incidence of post-transplantation recurrence. Heterozygous NPHS2 variants may
      play a role in atypical cases with mild, late-onset course, and recurrence after
      transplantation.

PMID- 15253709
TI  - Telomeric refinement of the MCKD1 locus on chromosome 1q21.
AB  - BACKGROUND: Autosomal-dominant medullary cystic kidney disease type 1 (MCKD1) is
      a tubulointerstitial nephropathy that causes renal salt wasting and end-stage
      renal failure in the sixth decade of life. The chromosomal locus for MCKD1 was
      localized to chromosome 1q21 in a Cyprotic kindred. In this report we describe
      further refinement of the critical genetic region by a recombination in a Belgian
      kindred. METHODS: Clinical data and blood samples of 33 individuals from a large
      Belgian kindred were collected and high-resolution haplotype analysis was
      performed. RESULTS: In the Belgian kindred linkage to the MCKD1 locus on
      chromosome 1q21 was found with a logarithm of odds (LOD) score significant for
      linkage. A recombination in individual III:7 for marker D1S2624 refines the
      critical genetic region to 2.1 Mb. In this kindred a wide variety of clinical
      symptoms and age of onset of renal failure was detected. CONCLUSION: We confirm
      the MCKD1 locus on chromosome 1q21 and show further refinement of the MCKD1 locus
      to 2.1 Mb. This allowed us to exclude another 17 genes as positional candidate
      genes.

PMID- 15253710
TI  - DNAzyme for TGF-beta suppressed extracellular matrix accumulation in experimental
      glomerulonephritis.
AB  - BACKGROUND: We developed an electroporation-mediated gene transfer method
      targeting glomerular mesangial cells. Injecting DNA solution via renal artery
      followed by electric pulses using tweezers-type electrodes could result in
      efficient transfection in mesangial cells. Therefore, this gene transfer system
      opened a feasible strategy to manipulate the function of several cytokines and
      growth factors in mesangial cells. Recently, a new generation of catalytic
      nucleic acid composed of DNA, named DNA enzyme (DNAzyme), has been developed.
      METHOD: We generated a DNAzyme (TGFDE) targeting transforming growth factor-beta1
      (TGF-beta1), and examined the therapeutic effect of TGFDE in vitro and in vivo.
      RESULTS: In cultured rat mesangial cells, treatment with TGFDE blocked TGF-beta1
      mRNA expression, and thereby suppressed type I collagen mRNA expression. Next, we
      introduced TGFDE or scrambled DNAzyme (TGFSCR) into anti-Thy-1 model of nephritic
      rats by electroporation 3 days after disease induction. Northern blot analysis
      and immunohistochemical staining demonstrated that glomerular message and protein
      expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and type I
      collagen were suppressed in TGFDE-transfected nephritic rats compared with
      untreated nephritic rats and TGFSCR-transfected rats on day 7. Consequently, we
      observed significant reduction in glomerular matrix score in TGFDE-transfected
      nephritic rats. CONCLUSION: Inhibition of TGF-beta1 expression by electroporation
      mediated DNAzyme transfer might be useful for the therapy of glomerulonephritis.

PMID- 15253711
TI  - Impairment of phenylalanine conversion to tyrosine in end-stage renal disease
      causing tyrosine deficiency.
AB  - BACKGROUND: Tyrosine is not considered an indispensable amino acid because in
      humans phenylalanine is converted to tyrosine. Recent human studies demonstrated
      that tyrosine production from phenylalanine occurs not only in liver but also in
      kidney. METHODS: Here we report results from studies, performed in end-stage
      renal disease (ESRD) patients and in healthy controls using [15N] phenylalanine
      and [2H4] tyrosine as tracers demonstrating the mechanism of tyrosine deficiency
      in patients with renal failure. RESULTS: Phenylalanine flux (an index of protein
      breakdown) was identical in both groups either before or during an infusion of
      amino acid mixture. In contrast, tyrosine flux (representing protein breakdown
      and tyrosine appearance from phenylalanine) and conversion of phenylalanine to
      tyrosine were lower in ESRD patients [2.05 +/- 0.30 micromol/kg fat-free mass
      (FFM)/hour and 2.59 +/- 0.52 micromol/kg FFM/hour, before and during amino acid
      infusion, respectively] than in the control subjects (4.07 +/- 0.54 micromol/kg
      FFM/hour and 5.53 +/- 0.86 micromol/kg FFM/hour, P <0.02, ESRD vs. controls,
      respectively). Plasma tyrosine concentrations in ESRD patients remained 40% lower
      than the controls during the postabsorptive state and following amino acid
      replacement. CONCLUSION: We conclude that reduced conversion of phenylalanine to
      tyrosine causes tyrosine deficiency in patients with ESRD prompting to propose
      that tyrosine replacement is potentially required in patients with ESRD.

PMID- 15253712
TI  - Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after
      unilateral ureteral obstruction.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) has been implicated in the
      development of renal fibrosis induced by unilateral ureteral obstruction (UUO).
      However, there is little information on signaling pathways mediating TGF-beta
      activity involved in molecular and cellular events leading to renal fibrosis
      induced by UUO. In this study, we sought to determine whether Smad3, a major
      signaling component of TGF-beta, mediated renal fibrosis induced by UUO. METHODS:
      Renal fibrosis, inflammation, and apoptosis induced by UUO were macroscopically
      and histologically compared between wild-type mice and Smad3 null mice. RESULTS:
      Gross appearance of the kidney after UUO showed relatively intact kidney in Smad3
      null mice [Smad3(-/-) mice] when compared with that of wild-type mice [Smad3(+/+)
      mice]. Renal interstitial fibrosis based on the interstitial area stained with
      Aniline-blue or Sirius red solution was significantly attenuated in the
      obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice.
      Deposition of type I and type III collagens were also significantly reduced in
      the obstructed kidney of Smad3(-/-) mice. In addition, the numbers of
      myofibroblasts, macrophages, and CD4/CD8 T cells infiltrated into the kidney
      after UUO were significantly attenuated in the obstructed kidney of Smad3(-/-)
      mice when compared with that of Smad3(+/+) mice. Furthermore, terminal
      deoxynucleotidyltransferase-mediated deoxyuridine triphosphate (dUTP) nick-end
      labeling (TUNEL) staining after UUO showed significantly reduced number of
      tubular apoptotic cells in the obstructed kidney of Smad3(-/-) mice when compared
      with that of Smad3(+/+) mice. Endogenous Smad pathway was activated in the
      obstructed kidney after UUO in wild-type mice as judged by the increase of
      phosphorylated Smad2 or phosphorylated Smad2/3-positive cells in renal
      interstitial area. CONCLUSION: Smad3 deficiency attenuated renal fibrosis,
      inflammation, and apoptosis after UUO, suggesting that Smad3 was a key molecule
      mediating TGF-beta activity leading to real fibrosis after UUO.

PMID- 15253713
TI  - TGF-beta induces proangiogenic and antiangiogenic factors via parallel but
      distinct Smad pathways.
AB  - BACKGROUND: Angiogenesis has a key role in numerous disease processes. One of the
      most important angiogenic factors is vascular endothelial growth factor (VEGF-A),
      whereas thrombospondin-1 (TSP-1) is a major antiangiogenic factor. Recent studies
      have shown that VEGF-A as well as TSP-1 is regulated by transforming growth
      factor-beta1 (TGF-beta1), but the mechanism remains unclear. METHODS: We examined
      the role of TGF-beta1 and its signaling pathways in mediating expression of these
      two molecules. Rat proximal tubular cells (NRK52E) were stimulated with TGF-beta1
      to induce VEGF-A and TSP-1 synthesis. To clarify roles of receptor-activated
      Smads (R-Smads), we blocked Smad signaling using overexpression of the inhibitory
      Smad, Smad7, and by using fibroblasts from wild-type or knockout mice. To confirm
      the antiantigenic role of Smads, soluble Flt-1 regulation in response to TGF
      beta1 was also examined. In addition, the effect of conditioned media from NRK52E
      and Smad knockout cells was examined on endothelial cell proliferation. RESULTS:
      Induction of VEGF-A and TSP-1 by TGF-beta1 in NRK52E cells was associated with
      activation of pathway-restricted R-Smads (Smad2 and 3) and blocking these Smads
      by overexpression of Smad7 blocked their induction. By using of Smad knockout
      cells, Smad3 was shown to have a key role in the stimulation of VEGF-A expression
      whereas Smad2 was critical for TSP-1 expression. Consistent with the hypothesis
      that Smad2 has an antiangiogenic function, we also demonstrated that Smad2, but
      not Smad3, mediated the expression of VEGF-A antagonist, soluble VEGF-A receptor
      sFlt-1, in response to TGF-beta1. Conditioned media from NRK52E, which was
      stimulated by TGF-beta1 for 24 hours, did not induce endothelial cell
      proliferation. However, conditioned media from Smad2 knockout induced endothelial
      cell proliferation, whereas endothelial cell proliferation was inhibited by Smad3
      knockout-derived conditioned media. CONCLUSION: R-Smads have distinct roles in
      mediating the expression of pro- and antiangiogenic growth factors in response to
      TGF-beta1.

PMID- 15253714
TI  - Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B
      vaccination in hemodialysis patients.
AB  - BACKGROUND: Dysfunctional antigen presentation may underlie the impaired antibody
      response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are
      considered to be the most important antigen presenting cells, but their presence
      and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony
      stimulating factor (GM-CSF) has been given successfully to hemodialysis patients
      to increase the proportion of responders to hepatitis B vaccination. Although GM
      CSF acts on both monocytes and dendritic cells, the mechanisms underlying its
      adjuvant quality are largely unknown. METHODS: In this study we analyzed
      monocytes and dendritic cells in the peripheral blood of hemodialysis patient
      that had responded to a standard hepatitis B vaccination procedure (responders),
      patients who had not responded (nonresponders), and healthy controls. The
      nonresponders were given two additional booster vaccines, both preceded by
      administration of GM-CSF the day before. RESULTS: After two booster vaccinations
      with GM-CSF, six out of seven patients developed a protective antibody response
      to hepatitis B. The memory T-cell response to tetanus toxoid was significantly
      lower in nonresponders compared to controls. The monocytes of dialysis patients
      and healthy controls showed a similar expression of relevant cell surface
      molecules. However, the numbers of circulating dendritic cells were on average
      50% reduced compared to healthy controls, with a further reduction after GM-CSF
      administration. This was accompanied by a decrease of T-cell proliferation in
      antigen presentation assays. Monocytes showed increased major histocompatibility
      complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting
      capacity remained unchanged. CONCLUSION: GM-CSF is an effective adjuvant for
      hepatitis B vaccination in primary nonresponding hemodialysis patients, but
      paradoxically decreases the antigen presenting capacity of peripheral blood
      mononuclear cells and the number of circulating dendritic cells.

PMID- 15253715
TI  - Mesangial cell expression of proto-oncogene Ets-1 during progression of
      mesangioproliferative glomerulonephritis.
AB  - BACKGROUND: Ets-1 is a transactivator of matrix-associated genes and key factor
      in neoangiogenesis. The expression of Ets-1 mRNA and protein was analyzed in
      healthy rat kidney and in a model for mesangioproliferative disease without and
      with inhibition of platelet-derived growth factor-B (PDGF-B) activity. METHODS:
      Immunohistochemistry was performed using a specific noncrossreacting anti-Ets-1
      antibody and included a counterstain with alpha-smooth muscle actin (alpha-SMA).
      Nuclear proteins from isolated glomeruli were analyzed by Western blotting.
      Changes in Ets-1 mRNA levels were detected by in situ hybridization and Northern
      blotting. PDGF-B antagonism was performed in nephritic rats by specific aptamers.
      RESULTS: The distribution of Ets-1-positive cells in healthy rats was
      heterogenous with exclusively nuclear staining of glomerular, tubular, and
      vascular cells. Profound changes were detected in the anti-Thy 1.1
      glomerulonephritis. Nuclear Ets-1 staining was intense in mesangial cells,
      whereas podocyte and endothelial cell staining was unchanged. The strongest
      signal was seen on days 2 to 7. By Western blotting of glomerular proteins a
      single 52 kD band was detected in healthy rats, which was increased 4.5-fold
      after disease induction. At the same time a 54 kD band appeared that most likely
      represents phosphorylated Ets-1. Ets-1 transcripts were detected in mesangial
      cells that include exon IV but lack exon VII. A concordant 6.4-fold up-regulation
      of mRNA was detected in glomeruli. Specific PDGF-B antagonism by aptamer
      treatment from days 3 to 7 after disease induction led to reduced Ets-1
      expression on day 7, correlating with decreased mesangial cell numbers.
      CONCLUSION: A temporal increase of mesangial cell Ets-1 expression correlates
      with mesangial cell activation in mesangioproliferative glomerulonephritis. PDGF
      B may partially contribute to the increased expression.

PMID- 15253717
TI  - Uremia causes endothelial progenitor cell deficiency.
AB  - BACKGROUND: Circulating bone marrow-derived endothelial progenitor cells (EPCs)
      promote vascular repair. Their number in peripheral blood correlates with
      endothelial function and cardiovascular risk in humans. We explored whether
      uremia influences the number of EPCs. METHODS: We assessed circulating CD34+
      hematopoietic progenitor cells in whole blood using flow cytometry and EPCs (in
      vitro assay) in 46 patients with advanced renal failure and in 46 age- and gender
      matched healthy subjects. Further, the effect of uremia on EPC differentiation
      was studied in vitro and in vivo. RESULTS: Both in renal patients (r= 0.34, P <
      0.02) and in healthy subjects (r= 0.32, P= 0.04) the number of EPCs was
      significantly correlated to the absolute number of CD34+ hematopoietic progenitor
      cells. Renal patients had significantly fewer EPCs than healthy subjects, however
      (167 +/- 15 cells/high power field vs. 235 +/- 17 cells/high power field; P <
      0.05). Uremic serum significantly (P < 0.05) inhibited EPC differentiation and
      functional activity in vitro. Amelioration of uremia after institution of renal
      replacement therapy in patients with terminal renal failure also significantly (P
      < 0.05) increased the number of EPCs. CONCLUSION: Uremia inhibits differentiation
      of EPCs. This may impair cardiovascular repair mechanisms in patients with renal
      failure.

PMID- 15253716
TI  - Dopamine D2-like receptor agonist bromocriptine protects against
      ischemia/reperfusion injury in rat kidney.
AB  - BACKGROUND: Dopamine, via activation of D1-like and D2-like receptors, plays an
      important role in the regulation of renal sodium excretion. Recently, we
      demonstrated that dopamine D2-like receptor agonist (bromocriptine) stimulates
      p44/42 mitogen-activated protein kinases (MAPKs) and Na+,K(+)ATPase (NKA)
      activity in proximal tubular epithelial cells. Since both these parameters are
      compromised in ischemia/reperfusion (I/R) injury to the kidney, we investigated
      whether bromocriptine protects against the injury. METHODS: In this study we used
      unilateral rat model of renal I/R injury. The Sprague-Dawley rats were divided
      into vehicle and bromocriptine groups. The vehicle and bromocriptine group was
      treated with vehicle and bromocriptine (500 microg/kg intravenously),
      respectively, 15 minutes before the induction of unilateral ischemia followed by
      24- or 48-hour reperfusion. At the end of 24 or 48 hours the animals were
      sacrificed to collect control and ischemic kidney cortices, in which necrosis,
      apoptosis, NKA activity, NKA alpha1 subunit expression, and p44/42 MAPK
      phosphorylation were measured. RESULTS: We found extensive necrosis, apoptosis,
      and decreased NKA activity (with no change in alpha1 subunit) in the ischemic
      kidney cortex compared to the nonischemic cortex from the vehicle-treated rats as
      early as 24 hours post-reperfusion. In contrast, I/R injury-induced necrotic,
      apoptotic, and decrease in NKA activity were absent in the outer cortex of
      bromocriptine-treated rats after 24 or 48 hours. Interestingly, we detected
      significantly higher phosphorylation of p44/42 MAPKs in control and ischemic
      kidneys of bromocriptine-treated rats compared to those of vehicle-treated rats.
      CONCLUSION: Therefore, bromocriptine, a D1-like receptor agonist, may protect
      against I/R injury to proximal tubules of the kidney, via p44/42 MAPK activation.

PMID- 15253718
TI  - Fibrin independent proinflammatory effects of tissue factor in experimental
      crescentic glomerulonephritis.
AB  - BACKGROUND: Tissue factor initiated glomerular fibrin deposition is an important
      mediator of injury in crescentic glomerulonephritis. Recent data have suggested
      noncoagulant roles for tissue factor in inflammation. METHODS: To test the
      hypothesis that in addition to its effects in initiating coagulation, tissue
      factor has proinflammatory effects in glomerulonephritis, rabbits given
      crescentic anti-glomerular basement membrane (GBM) antibody-induced
      glomerulonephritis were defibrinogenated with ancrod. One group of
      defibrinogenated rabbits was also given anti-tissue factor antibodies.
      Comparisons were made between these groups, as well as a third group that was
      neither defibrinogenated with ancrod nor given anti-tissue factor antibodies.
      RESULTS: Defibrinogenation alone abolished glomerular fibrin deposition, reduced
      crescent formation, and limited renal impairment (ancrod-treated, serum
      creatinine 274 +/- 37 micromol/L; untreated 415 +/- 51 micromol/L; P < 0.01).
      Tissue factor inhibition in defibrinogenated rabbits resulted in further
      protection of renal function (creatinine 140 +/- 19 micromol/L, P < 0.01) and
      reduced proteinuria (0.4 +/- 0.2g/day, untreated 2.6 +/- 0.4 g/day, P <0.01),
      which was significantly increased by defibrinogenation alone (ancrod-treated, 5.6
      +/- 1.2 g/day). Anti-tissue factor antibodies (but not defibrinogenation alone)
      attenuated glomerular T-cell and macrophage recruitment, and major
      histocompatibility complex (MHC) class II expression. CONCLUSION: These results
      demonstrate important proinflammatory effects of tissue factor in crescentic
      glomerulonephritis that are fibrin independent and provide in vivo evidence for
      tissue factor's proinflammatory effects on MHC class II expression and leukocyte
      accumulation.

PMID- 15253719
TI  - Proximal tubule cells stimulated by lipopolysaccharide inhibit macrophage
      activation.
AB  - BACKGROUND: Tubule cells can produce a variety of cytokines, extracellular matrix
      (ECM) components, and adhesion molecules in vitro and in vivo. It is generally
      assumed that stimulated tubule cells are proinflammatory and at least partially
      responsible for interstitial inflammation. However, the overall effect of tubular
      cells on interstitial cells is unknown. In this study, pro- and anti-inflammatory
      cytokine production and net effects on macrophages of tubule cells activated by
      lipopolysaccharide (LPS) were examined. METHODS: Tubule cells stimulated with LPS
      expressed tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-12,
      monocyte chemoattractant protein-1 (MCP-1), IL-10, and transforming growth factor
      beta (TGF-beta). Conditioned media were collected from confluent monolayers of
      rat tubule cells stimulated, or not, by LPS for 4 and 18 hours, respectively.
      Macrophages were cultured with conditioned media and/or LPS (0.5 microg/mL) for
      18 hours. RESULTS: TNF-alpha and IL-lbeta mRNA of macrophages stimulated by LPS
      increased more than fivefold when cultured with control conditioned media from
      unstimulated tubule cells. Surprisingly, TNF-alpha and IL-lbeta levels of
      macrophages stimulated by LPS were not increased when cultured with conditioned
      media from activated tubule cells. Neutralizing antibodies to IL-10 and TGF-beta
      were used to define the inhibitory component(s) in conditioned medium. Anti-IL
      10, but not anti-TGF-beta, abolished partially the inhibitory effects of
      conditioned media on macrophages. CONCLUSION: Tubule cells produce both pro- and
      anti-inflammatory cytokines and the net effect, partially explained by IL-10, of
      tubule cells activated with LPS is to inhibit activity of macrophages. Thus, the
      net effect of activated tubule cells on interstitial pathology may in certain
      circumstances, be anti- rather than pro-inflammatory.

PMID- 15253720
TI  - Estimation of podocyte number: a comparison of methods.
AB  - BACKGROUND: The podocyte is the focus of much research into the mechanisms of
      renal disease progression, and the number of podocytes per glomerulus has thus
      become a parameter of much interest. When counting podocytes, the actual particle
      counted is the cell nucleus. The majority of published studies estimating
      podocyte number have used the method of Weibel and Gomez (1962). This makes
      assumptions about the shape and size of the cell nuclei and therefore has an
      inherent bias. In our studies we have used a more recent stereologic method--the
      disector/fractionator--that makes no assumptions about the shape or size of the
      cell nuclei and is therefore free of bias. METHODS: We set out to compare the two
      methods, in both type 1 diabetic patients and normal controls, to determine
      whether eliminating bias and thus improving accuracy had any effect on the
      overall results. The Weibel-Gomez method estimates cell number from a single
      section through the glomerulus, whereas the disector/fractionator requires the
      glomerulus to be serially sectioned. RESULTS: There was no significant difference
      between mean values obtained by the two methods, providing that the Weibel-Gomez
      estimate was performed on electron micrographs. However, the overall variance was
      high for all groups of patients, independent of the method employed. CONCLUSION:
      Although the disector/fractionator is the theoretic gold standard method for
      podocyte number estimation, comparable estimates can be obtained by the Weibel
      Gomez method provided they are made from electron micrographs. Thus the technical
      resources available may determine the choice of method employed. Investigators
      should be aware of the high degree of variability in the estimate, particularly
      when trying to detect small changes in podocyte number.

PMID- 15253721
TI  - AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and
      glomerulosclerosis in the Imai rat.
AB  - BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which
      leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal
      failure. We evaluated the effects of angiotensin II receptor type 1 (AT
      1)blockade, and compared the results with the effects of the administration of
      hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor. All treatments were started at 10 weeks of age when the rats
      were already proteinuric and continued for 6 months when rats were sacrificed.
      METHODS: The following groups (N= 6 each) were studied: (1) control Sprague
      Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai +
      angiotensin II receptor blockade (ARB) group that received olmesartan (10
      mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin
      (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received
      both ARB and pravastatin. Lipid profile, renal function, and structure were
      assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited
      heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked
      glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia.
      Pravastatin treatment alone led to a significant, but partial improvement of
      hyperlipidemia and renal disease. The ARB treatment alone or in combination with
      pravastatin resulted in normalization of the blood pressure, urinary protein
      excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs),
      very low-density lipoproteins (VLDLs), and albumin concentrations and renal
      function. Significant glomerulosclerosis was prevented and tubulointerstitial
      injury and immune cell infiltration were reduced by long-term AT-1 blockade.
      CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria,
      hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.

PMID- 15253722
TI  - Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an
      increase in urinary oxalate excretion.
AB  - BACKGROUND: Unabsorbed fat and bile acids may react with calcium in the
      intestinal lumen, limiting the amount of free calcium binding with oxalate and
      thereby raising intestinal oxalate absorption leading to hyperoxaluria. The aim
      of the present study was to determine whether orlistat (Xenical), a
      gastrointestinal lipase inhibitor, might increase urinary oxalate in an
      experimental rat model. METHODS: Thirty-nine male adult Wistar rats were fed a
      standard diet alone (controls) or supplemented with either 2% sodium oxalate
      (NaOx) or 3.2 mL of soy oil, or with both (NaOx + soy oil) for 4 weeks (diet
      period). Orlistat (16 mg/day) was added to the diet from the 5th to the 8th week
      (diet + orlistat period). Urinary oxalate (uOx), calcium (uCa), magnesium (uMg),
      and citrate (uCit) were determined and the ion-activity product of calcium
      oxalate [AP (CaOx) index(rat)] was estimated. RESULTS: Compared to baseline uOx
      significantly increased after diet + orlistat in controls (0.64 +/- 0.1 mg/24
      hours vs. 0.56 +/-0.1 mg/24 hours), soy oil (0.80 +/- 0.3 mg/24 hours vs. 0.49 +/
      0.2 mg/24 hours), and NaOx (2.48 +/- 0.8 mg/24 hours vs. 0.57 +/- 0.2 mg/24
      hours), but the most marked increase occurred in NaOx + soy oil (3.87 +/- 0.7
      mg/24 hours vs. 0.47 +/- 0.1 mg/24 hours). All groups except controls presented a
      significant reduction in uCa and uMg. Orlistat induced a significant increase in
      AP (CaOx) index(rat) compared, respectively, to baseline and to the diet period
      in NaOx (4.52 +/- 2.34 mg/24 hours vs. 0.94 +/- 0.86 and 1.53 +/- 0.93 mg/24
      hours) and NaOx + soy oil (6.49 +/- 4.03 mg/24 hours vs. 0.54 +/- 0.17 and 1.76
      +/- 1.32 mg/24 hours). CONCLUSION: These data suggest that the use of lipase
      inhibitors, especially under a diet rich in oxalate alone or associated with fat,
      leads to a significant and marked increase in urinary oxalate and a slight
      reduction in uCa and uMg that, taken together, resulted in an increase in AP
      (CaOx) index(rat), elevating the risk of stone formation.

PMID- 15253723
TI  - EPO and alpha-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs
      and sodium transporters in rat kidney.
AB  - BACKGROUND: Ischemia-induced acute renal failure (ARF) is known to be associated
      with significant impairment of urinary concentrating ability and down-regulation
      of renal aquaporins (AQPs) and sodium transporters in rats. We tested whether
      treatment with erythropoietin (EPO) or alpha-melanocyte-stimulating hormone
      (alpha-MSH) in combination with EPO reduces the renal ischemia/reperfusion (I/R)
      injury and prevents the down-regulation of renal AQPs and major sodium
      transporters. METHODS: I/R-induced ARF was established in rats by 40-minute
      temporary bilateral obstruction of renal arteries, and rats were kept in
      metabolic cages for urine measurements. After 2 or 4 days following EPO and/or
      alpha-MSH treatment, kidneys were removed to determine the expression levels of
      AQPs and sodium transporters by semiquantitative immunoblotting. RESULTS: Rats
      with ARF showed significant renal insufficiency, increased urine output, and high
      fractional excretion of urinary sodium. Consistent with this, immunoblotting and
      immunocytochemistry revealed that the kidney expression of AQPs (AQP-1, -2 and 
      3) and sodium transporters [Na,K-ATPase, rat type 1 bumetanide-sensitive Na-K-2Cl
      cotransporter (BSC-1), Na/H exchanger type 3 (NHE3), and thiazide-sensitive
      sodium chloride cotransporter (TSC)] in ARF rats was significantly decreased
      compared to sham-operated control rats. In contrast, EPO treatment at the time of
      ischemia of rats with ARF significantly prevented the ischemia-induced down
      regulation of renal AQPs and sodium transporters and in parallel improved the
      urinary concentrating capability and renal sodium reabsorption. Importantly,
      similar effects were observed following the initiation of EPO or alpha-MSH
      treatment 4 hours after the onset of ischemia injury. Moreover, the combination
      of EPO with alpha-MSH potentiated the beneficial effects of single compound
      treatment. CONCLUSION: EPO and/or alpha-MSH treatment significantly prevent I/R
      induced injuries such as urinary-concentrating defects and down-regulation of
      renal AQPs and sodium transporters.

PMID- 15253724
TI  - Signaling path of the action of AVP on distal K+ secretion.
AB  - BACKGROUND: Previous studies from our laboratory have shown that luminal
      perfusion with arginine vasopressin (AVP) stimulates distal tubule secretory
      potassium flux (JK) via V1 receptors (Am J Physiol 278:F809-F816, 2000). In the
      present work, we investigate the cell signaling mechanism of this process.
      METHODS: In vivo stationary microperfusion was performed in rat cortical distal
      tubules and luminal K+ was measured using double K+ resin/reference
      microelectrodes. RESULTS: In control conditions, JK was 0.71 +/- 0.05 nmol.cm(
      2).second(-1); this process was inhibited (14%) by 10(-5) mol/L 8-bromo-cyclic
      adenosine monophosphate (cAMP), and increased by 35% with 10(-8) mol/L phorbol
      ester [phorbol12-myristate 13-acetate (PMA), which activates protein kinase C
      (PKC)]. During luminal perfusion with 10(-11) mol/L AVP, JK increased to 0.88 +/-
      0.08 nmol.cm(-2).seconds(-1). In the presence of 10(-11) mol/L AVP, JK was not
      affected by 10(-4) mol/L H89, a blocker of protein kinase A (PKA), but was
      inhibited (45%) by 10(-5) mol/L staurosporine, an inhibitor of PKC, and by 41%
      during perfusion with 5 x 10(-5) mol/L of the cell Ca2+ chelator bis (2
      aminophenoxy) ethane-tetraacetic acid (BAPTA). In order to study the role of
      Ca(2+)-dependent K channels in the luminal hormonal action, the tubules were
      perfused with 5 mmol/L tetraethylammonium chloride (TEA) or 10(-7) mol/L
      iberiotoxin, in the presence of AVP, and JK was significantly reduced by both
      agents. Iberiotoxin reduced AVP-stimulated JK by 36.4%, and AVP-independent JK
      (after blocking V1 receptors) by only 16%. CONCLUSION: The results suggest that
      the luminal V1-receptor effect of AVP on JK was mediated by the phospholipase C
      (PLC)/Ca2+/PKC signaling path and not byadenylate cyclase/cAMP/PKA, therefore
      probably acting on maxi-potassium channels.

PMID- 15253725
TI  - Nitric oxide and renal nerves: comparison of effects on renal circulation and
      sodium excretion in anesthetized rats.
AB  - BACKGROUND: An array of vasoconstrictor and vasodilator agents have the potential
      to control intrarenal circulation; however, their relative functional importance
      is unclear. We compared here the importance of nitric oxide and renal nerves in
      studies involving sequential blockade of nitric oxide synthesis and renal
      denervation. METHODS: In anesthetized rats, N-nitro-L-arginine methylester (L
      NAME) was used for nonselective inhibition of nitric oxide synthesis and 7
      nitroindazole (7-NI) for inactivation of neuronal isoform of nitric oxide
      synthase (nNOS). Acute unilateral renal denervation was performed noninvasively
      enabling observation of rapid changes. Renal cortical and medullary blood flow
      was determined by laser Doppler flowmetry. RESULTS: L-NAME decreased medullary
      blood flow and cortical blood flow, by 22% to 24%, whereas after 7-NI, medullary
      blood flow decreased by 22% and cortical blood flow about 10% (all changes
      significant). In untreated rats denervation significantly increased cortical
      blood flow (10% to 15%) but not medullary blood flow. In rats treated with L-NAME
      denervation partly prevented the post-inhibitor decrease in cortical blood flow
      but not in medullary blood flow. After 7-NI treatment, the decrease in cortical
      blood flow and medullary blood flow did not occur or a partial restoration of
      flow was seen. The denervation natriuresis was intact under L-NAME but attenuated
      following 7-NI. CONCLUSION: A reduction of medullary blood flow after 7-NI,
      similar as after L-NAME, suggests that nitric oxide generated by nNOS is mainly
      responsible for adequate perfusion of the medulla whereas activity of nNOS and
      other isoform(s) is required to maintain cortical blood flow. Renal denervation
      partly restored cortical blood flow reduced by nitric oxide blockade. For
      medullary blood flow, such restoration was seen only after inactivation of nNOS
      alone, suggesting an intrinsic interaction of this isoform and renal nerves.

PMID- 15253726
TI  - Cytokine gene expression profiles in kidney medulla and cortex of obese
      hypertensive dogs.
AB  - BACKGROUND: The molecular mechanisms linking abnormal kidney function and obesity
      hypertension are poorly understood. This study compared gene expression profiles
      in the kidney medulla and cortex of obese and lean dogs. METHODS: Lean dogs (N=
      4) were fed a standard kennel ration and obese dogs (N= 4) were fed the standard
      diet plus 0.5 to 0.9 kg of cooked beef fat per day for 10 weeks. The dogs were
      instrumented for continuous monitoring of mean arterial pressure (MAP), heart
      rate, glomerular filtration rate (GFR), and effective renal plasma flow (RPF).
      The relative mRNA levels of 375 genes in renal cortex and medulla were determined
      simultaneously using cDNA membrane arrays (R&D Systems). RESULTS: The high fat
      diet increased body weight by 57% and MAP increased by 24 mm Hg (112 +/- 1 mm Hg
      vs. 88 +/- 3 mm Hg) in obese compared to lean dogs. In obese dogs, expression of
      11 and 13 genes changed significantly (N= 4; P < 0.05) in the renal medulla and
      the cortex, respectively, relative to the lean dogs. Differences in renal gene
      expression profiles between lean and obese dogs were closely related to
      functional pathways, including those associated with sympathetic activation,
      inflammatory response, matrix formation, angiogenesis, endothelial dysfunction,
      attenuated actions of leptin, and attenuated cell survival. CONCLUSION: A high
      fat diet in dogs is associated with marked changes in renal gene expression
      profiles that provide potential molecular links to pathways associated with
      altered renal function and structure in obesity hypertension.

PMID- 15253727
TI  - Tissue kallikrein attenuates salt-induced renal fibrosis by inhibition of
      oxidative stress.
AB  - BACKGROUND: High salt intake induces hypertension, cardiac hypertrophy, and
      progressive renal damage. Progressive renal injury is the consequence of a
      process of destructive fibrosis. Using gene transfer approach, we have shown that
      the tissue kallikrein-kinin system (KKS) plays an important role in protection
      against renal injury in several hypertensive rat models. In this study, we
      further investigated the effect and potential mechanisms mediated by kallikrein
      on salt-induced renal fibrosis. METHODS: Adenovirus harboring the human tissue
      kallikrein gene was delivered intravenously into Dahl salt-sensitive (DSS) rats
      on a high salt diet for 4 weeks. Two weeks after gene delivery, the effect of
      kallikrein on renal fibrosis was examined by biochemical and histologic analysis.
      RESULTS: Kallikrein gene delivery resulted in reduced blood urea nitrogen (BUN),
      urinary protein and albumin levels in DSS rats on a high salt diet. Expression of
      recombinant human tissue kallikrein was detected in the sera and urine of rats
      injected with the kallikrein gene. Histologic investigation showed that
      kallikrein gene delivery significantly reduced glomerular and tubular fibrosis
      scores and collagen deposition, as well as renal cell proliferation, compared to
      rats on a high salt diet injected with control virus. Kallikrein gene transfer
      significantly increased nitric oxide and cyclic guanosine monophosphate (cGMP)
      levels in conjunction with reduced salt-induced nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase
      activity, superoxide production, transforming growth factor-beta1 (TGF-beta1)
      mRNA and protein levels, and TGF-beta1 immunostaining. CONCLUSION: These results
      indicate that tissue kallikrein protects against renal fibrosis in hypertensive
      DSS rats through increased nitric oxide bioavailability and suppression of
      oxidative stress and TGF-beta expression.

PMID- 15253728
TI  - Activation of mesangial cell MAPK in response to homocysteine.
AB  - BACKGROUND: Alteration in mesangial cell function is central to the progression
      of glomerular disease in numerous models of chronic renal failure (CRF). Animal
      models of chronic glomerular disease are characterized by mesangial cell
      proliferation and elaboration of extracellular matrix protein (ECM), resulting in
      glomerulosclerosis. Elevated plasma levels of homocysteine (Hcy) are seen in both
      animal models and humans with CRF, and have been proposed to contribute to the
      high prevalence of vascular disease in this group. Some of the pathogenetic
      effects of Hcy are thought to be mediated via the induction of endoplasmic
      reticulum stress. Thus, Hcy effects on mesangial cells could contribute to the
      progression of CRF. Previous work has shown Hcy- mediated induction of Erk
      mitogen-activated protein kinase (MAPK) in vascular smooth muscle cells (VSMCs).
      Erk induces increases in activator protein-1 (AP-1) transcription factor activity
      which may augment mesangial cell proliferation and ECM protein production.
      Consequently, we studied the effect of Hcy on mesangial cell Erk signaling.
      METHODS: Mesangial cells were exposed to Hcy after 24 hours of serum starvation
      and Erk activity assessed. Nuclear translocation of phospho-Erk was visualized by
      confocal microscopy. AP-1 nuclear protein binding was measured in response to Hcy
      by mobility shift assay. Hcy-induced mesangial cell calcium flux was measured in
      Fura-2 loaded cells. Mesangial cell DNA synthesis in response to Hcy was assessed
      by [3H]-thymidine incorporation and proliferation by Western blotting for
      proliferating cell nuclear antigen (PCNA). Expression of endoplasmic reticulum
      stress response genes were determined by Northern and Western analysis. RESULTS:
      Hcy led to an increase in Erk activity that was maximal at 50 micromol/L and 20
      minutes of treatment. Subsequent experiments used this concentration and time
      point. Erk activity in response to Hcy was insensitive to n-acetylcysteine and
      catalase, indicating oxidative stress did not play a role. However, Hcy50
      micromol/L induced a brief increase in intracellular mesangial cell calcium
      within 5 minutes, and the calcium ionophores A23187 and ionomycin increased Erk
      activity while chelation of intracellular calcium with BAPTA-AM abrogated the Erk
      response to Hcy. Confocal microscopy of activated Erk nuclear translocation
      mirrored these results as did mesangial cell nuclear protein binding to AP-1
      consensus sequences. Hcy- induced increases in thymidine incorporation and PCNA
      expression at 24 hours were Erk dependent. The expression of endoplasmic
      reticulum stress response genes was significantly elevated by Hcy in an Erk
      dependent manner. CONCLUSION: Hcy increases Erk activity in mesangial cells via a
      calcium-dependent mechanism, resulting in increased AP-1 nuclear protein binding,
      cell DNA synthesis and proliferation and induction of endoplasmic reticulum
      stress. These observations suggest potential mechanisms by which Hcy may
      contribute to progressive glomerular injury.

PMID- 15253729
TI  - Clinical implications of mutation analysis in primary hyperoxaluria type 1.
AB  - BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate
      metabolism with an extensive clinical and genetic heterogeneity. Although over 50
      disease-causing mutations have been identified, the relationship between genotype
      and clinical outcome remains unclear. The aim of this study was to determine this
      association in order to find clues for improvement of patient care. METHODS: AGXT
      mutation analysis and assessment of biochemical characteristics and clinical
      outcome were performed on patients from a Dutch PH1 cohort. RESULTS: Thirty-three
      of a cohort of 57 PH1 patients, identified in The Netherlands over a period of 30
      years, were analyzed. Ten different mutations were found. The most common
      mutations were the Gly170Arg, Phe152Ile, and the 33insC mutations, with an allele
      frequency of 43%, 19%, and 15%, respectively. Homozygous Gly170Arg and Phe152Ile
      mutations were associated with pyridoxine responsiveness and a preserved renal
      function over time when treatment was timely initiated. All patients homozygous
      for the 33insC mutation had end-stage renal disease (ESRD) before the first year
      of age. In two unrelated patients, a new Val336Asp mutation was found coupled
      with the Gly170Arg mutation on the minor allele. We also found 3 patients
      homozygous for a novel Gly82Arg mutation with adverse outcome in 2 of them.
      CONCLUSION: Early detection of Gly170Arg and Phe152Ile mutations in PH1 has
      important clinical implications because of their association with pyridoxine
      responsiveness and clinical outcome. The association of a homozygous 33insC
      mutation with severe infantile ESRD, resulting in early deaths in 2 out of 3
      cases, warrants a choice for prenatal diagnostics in affected families.

PMID- 15253730
TI  - Treating anemia early in renal failure patients slows the decline of renal
      function: a randomized controlled trial.
AB  - BACKGROUND: Erythropoietin is known to improve outcomes in patients with anemia
      from chronic renal disease. However, there is uncertainty about the optimal
      timing of initiation of erythropoietin treatment in predialysis patients with non
      severe anemia. METHODS: We conducted a randomized controlled trial of early
      versus deferred initiation of erythropoietin in nondiabetic predialysis patients
      with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early
      treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with
      appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred
      treatment arm would start erythropoietin only when hemoglobin decreased to <9
      g/dL. The primary end point was a composite of doubling of creatinine, renal
      replacement, or death. RESULTS: Eighty-eight patients were randomized (early
      treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5
      months. During follow-up, 13 versus 23 patients reached the primary end point in
      the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching
      an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the
      adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold
      (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar
      regardless of the baseline hemoglobin and proteinuria. No patients had any severe
      adverse events. CONCLUSION: Early initiation of erythropoietin in predialysis
      patients with non-severe anemia significantly slows the progression of renal
      disease and delays the initiation of renal replacement therapy.

PMID- 15253731
TI  - The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal
      renal tubular acidosis.
AB  - BACKGROUND: Urine pH during acidemia and urine PCO2 upon alkalization both may be
      useful to indicate H+ secretion from collecting ducts. The urine anion gap has
      been used to detect urinary NH4+ for differential diagnosis of hyperchloremic
      metabolic acidosis. We have previously demonstrated that the lack of normal H(+)
      ATPase may underlie secretory defect distal renal tubular acidosis (dRTA). In
      this study we evaluated the diagnostic value of the urine-blood (U-B) PCO2 in
      H(+)-ATPase defect dRTA, and compared it with that of urine pH and urine anion
      gap during acidemia. METHODS: In H(+)-ATPase defect dRTA, the diagnostic values
      of three urinary parameters were evaluated: (1) urine pH measured after acid
      (NH4Cl) loading; (2) urine-to-blood carbon dioxide tension gradient (U-B PCO2)
      during alkali (NaHCO3) loading; and (3) urine anion gap during acidemia.
      Seventeen patients were diagnosed as having H(+)-ATPase defect dRTA based on
      reduced urinary NH4+ and an absolute decrease in H(+)-ATPase immunostaining in
      intercalated cells on renal biopsy. Eight patients with non-dRTA renal disease
      served as control patients. RESULTS: Upon NaHCO3 loading, U-B PCO2 was < or =30
      mm Hg in all 17 dRTA patients and >30 mm Hg in all 8 control patients. With NH4Cl
      loading, urine pH was >5.4 in 15 of 17 dRTA patients and < or =5.4 in 7 of 8
      control patients, and the urine anion gap was >5 mmol/L in 13 of 17 dRTA patients
      and< or =5 mmol/L in 6 of 8 control patients. Therefore, the sensitivity and
      specificity of U-B PCO2 < or =30 mm Hg during NaHCO3 loading were both 100%,
      whereas those of urine pH >5.4 or urine anion gap >5 mmol/L during NH4Cl loading
      were below 90%. In control patients, the U-B PCO2 was found to be well correlated
      with the urinary NH4+ (r= 0.79, P < 0.05). CONCLUSION: The U-B PCO2 during NaHCO3
      loading is an excellent diagnostic index of H(+)-ATPase defect dRTA.

PMID- 15253732
TI  - Antihypertensive and antiproteinuric efficacy of ramipril in children with
      chronic renal failure.
AB  - BACKGROUND: While the antihypertensive and renoprotective potency of angiotensin
      converting enzyme (ACE) inhibitors is well-established in adults with
      hypertension and/or chronic renal failure, little experience exists in pediatric
      chronic kidney disease. METHODS: As part of a prospective assessment of the
      renoprotective efficacy of ACE inhibition and intensified blood pressure (BP)
      control, 397 children (ages 3 to 18 years) with chronic renal failure [CRF;
      glomerular filtration rate (GFR) 11 to 80 mL/min/1.73 m2] and elevated or high
      normal BP received ramipril (6 mg/m2) following a 6-month run-in period including
      a two-month washout of any previous ACE inhibitors. Drug efficacy was assessed by
      two monthly office BP and proteinuria assessments, and by ambulatory BP
      monitoring at start and after 6 months of treatment. RESULTS: In the 352 patients
      completing six months of treatment, 24-hour mean arterial pressure (MAP) had
      decreased by a mean of 11.5 mm Hg (-2.2 SDS) in initially hypertensive subjects,
      but only by 4.4 mm Hg (-0.8 SDS) in patients with initially normal BP. A linear
      correlation was found between MAP at baseline and the change of MAP during
      treatment (r= 0.51; P < 0.0001). The antihypertensive response was independent of
      changes in concomitant antihypertensive medication or underlying renal disease.
      BP was reduced with equal efficacy during day- and nighttime. Urinary protein
      excretion was reduced by 50% on average, with similar relative efficacy in
      patients with hypo/dysplastic nephropathies and glomerulopathies. The magnitude
      of proteinuria reduction depended on baseline proteinuria (r= 0.32, P < 0.0001),
      and was correlated with the antihypertensive efficacy of the drug (r= 0.22, P <
      0.001). The incidence of rapid rises in serum creatinine and progression to end
      stage CRF during treatment did not differ from the pretreatment observation
      period. Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued
      in three patients due to symptomatic hypotension or hyperkalemia. Hemoglobin
      levels decreased by 0.6 g/dL in the first two treatment months and remained
      stable thereafter. CONCLUSION: Ramipril appears to be an effective and safe
      antihypertensive and antiproteinuric agent in children with CRF-associated
      hypertension. The BP lowering and antiproteinuric effects are greatest in
      severely hypertensive and proteinuric children.

PMID- 15253733
TI  - Clinical implications of abundant calcium phosphate in routinely analyzed kidney
      stones.
AB  - BACKGROUND: To better portray the clinical phenotype of kidney stone patients
      with high calcium phosphate (CaP) stone abundance, we present here clinical and
      laboratory findings of large numbers of stone formers (SF) with stone CaP ranging
      from 0% to 100%. Our purpose was to inform clinicians and highlight areas that
      seem to deserve further research. METHODS: We calculated average percent CaP
      (CaP%) in all stones of 1201 patients, and classified them into CaOx (N= 1011) or
      CaP (N= 190). Sex differences, stone formation rates, urine stone risk factors,
      extracorporeal shock wave lithotripsy (ESWL) treatments, and relapse during
      treatment were quantified in relation to stone CaP content. RESULTS: CaP% has
      risen for three decades, especially among women. ESWL rates adjusted for numbers
      of stones and duration of stone disease were higher in CaP SF (0.6 vs. 1.86 and
      0.73 vs. 1.82, CaOx vs. CaP, men and women, respectively, P < 0.001), and
      especially when stones contained brushite (2.90 vs. 1.02 and 3.11 vs. 1.35,
      brushite vs. not, males and females, respectively, P < 0.001). Urine pH and CaP
      supersaturation rose in proportion to CaP% in a dose response manner. Relapse
      rates of CaP and CaOx SF did not differ, and both did well with medical
      prevention. CONCLUSION: Stone CaP% has risen for three decades. CaP SF,
      particularly with brushite stones, receive more ESWL treatments than CaOx SF, not
      explained by stone number or duration of stone disease. Urine supersaturations
      explain the high CaP%. High CaP% does not hamper medical stone prevention.

PMID- 15253734
TI  - Ionic dialysance allows an adequate estimate of urea distribution volume in
      hemodialysis patients.
AB  - BACKGROUND: An adequate estimation of urea distribution volume (V) in
      hemodialysis patients is useful to monitor protein nutrition. Direct dialysis
      quantification (DDQ) is the gold standard for determining V, but it is
      impractical for routine use because it requires equilibrated postdialysis plasma
      water urea concentration. The single pool variable volume urea kinetic model
      (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality
      Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it
      requires a correct estimate of dialyser urea clearance. METHODS: Ionic dialysance
      (ID) may accurately estimate dialyzer urea clearance corrected for total
      recirculation. Using ID as input to SPVV-UKM, correct V values are expected when
      end-dialysis plasma water urea concentrations are determined in the end-of
      session blood sample taken with the blood pump speed reduced to 50 mL/min for two
      minutes (U(pwt2')). The aim of this study was to determine whether the V values
      determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those
      determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric
      hemodialysis patients were studied. RESULTS: V(DDQ) was 26.3 +/- 5.2 L; V(ID) was
      26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not
      statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated
      using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3
      +/- 3.3 L, which is statistically significant (P < 0.001). CONCLUSION:
      Anthropometric-based V values overestimate urea distribution volume calculated by
      DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents
      the problem of delayed postdialysis blood samples.

PMID- 15253735
TI  - Effect of renal transplantation in childhood on longitudinal growth and adult
      height.
AB  - BACKGROUND: Severe growth failure is frequently observed in children suffering
      from end-stage renal disease (ESRD). METHODS: We analyzed the effect of renal
      transplantation (RTx) on longitudinal growth and final height in 37 children (19
      girls) with ESRD with a mean follow-up of 8.5 years. The mean age at RTx was 11.3
      years. RESULTS: In children transplanted before start of puberty, mean height
      velocity increased significantly from 4.9 to 8.0 cm/year (P < 0.01), resulting in
      an increase in standardized height of 0.6 SD within two years post RTx. Although
      peak height velocity during puberty was significantly increased compared with
      healthy children, total pubertal height gain was reduced by 20% because of its
      shortened duration. Mean standardized height significantly increased from the
      time of RTx until final height by 1.3 SD and 0.7 SD in children transplanted
      before and after start of puberty, respectively. Mean adult height (boys 170 cm;
      girls 151 cm) was normal (> -2 SD) in 68% of patients. Change in standardized
      height from RTx until adult height was associated with initial degree of stunting
      and glomerular filtration rate (GFR; cumulative r2 0.49). Total pubertal height
      gain was associated with the age at start of puberty, GFR, and age at RTx
      (cumulative r2 0.57). CONCLUSION: RTx in children with ESRD induces moderate
      catch-up growth during the prepubertal growth period. However, final height is
      reduced in about one third of patients due to the reduced pubertal height gain
      and preexisting height deficit at the time of RTx.

PMID- 15253736
TI  - Locking of tunneled hemodialysis catheters with gentamicin and heparin.
AB  - INTRODUCTION: Catheter-related infection (CRI) is a major cause of morbidity and
      mortality in patients receiving hemodialysis. Antibiotic locking of these
      catheters has been shown to increase both the success of systemic antibiotic
      treatment in line sepsis, and to reduce the incidence of sepsis. We have studied
      the use of gentamicin locking of catheters (in combination with standard heparin
      rather than previously reported citrate) to reduce CRI rates. Furthermore, we
      have investigated the effects of this strategy on epoetin requirements and
      vascular access function. METHODS: Fifty patients were studied. Patients were
      randomized to catheter-restricted filling with either standard heparin (5000
      IU/mL) alone, or gentamicin and heparin (5 mg/mL). Epoetin requirements and
      hemoglobin response were monitored over the study period. RESULTS: The gentamicin
      locked group suffered only one infective episode (0.3/1000 catheter days)
      compared to 10 episodes in six patients in the heparin alone group (4/1000
      catheter days, P= 0.02). The isolated organisms were equally split between
      Staphylococcal species and coliforms. There were no statistically significant
      differences in delivered dialysis dose (Kt/V) or QA between the two groups. Use
      of antibiotic locking was associated with both a higher mean hemoglobin (10.1 +/
      0.14 g/dL vs. 9.2 +/- 0.17 g/dL in the heparin group, P= 0.003) and a lower mean
      epoetin dose (9000 +/- 734 IU/week vs. 10790 +/-615 IU/week in the heparin group,
      P= 0.04). CONCLUSION: The practice of locking newly inserted tunneled central
      venous catheters with gentamicin and heparin is an effective strategy to reduce
      line sepsis rates, and is associated with beneficial effects on epoetin
      requirements.

PMID- 15253737
TI  - Pulmonary calcification in hemodialysis patients: correlation with pulmonary
      artery pressure values.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients receiving chronic
      hemodialysis (HD) via an arteriovenous (A-V) access often develop unexplained
      pulmonary hypertension (PHT). This study evaluated the role of pulmonary
      calcification (PC) in this phenomenon. METHODS: The clinical manifestations,
      systolic pulmonary artery pressure (PAP) values measured by Doppler
      echocardiography and the presence and the extent of PC expressed by lung uptake
      of 99mTc-MDP bone scintigraphy, were studied in 49 patients with ESRD receiving
      chronic HD therapy via A-V access. The correlation between PC and PHT was
      investigated. RESULTS: There were 36 men and 13 women with a mean age of 61.7 +/-
      13.2 years receiving HD therapy for 38.2 +/- 43.7 months. Twenty (40.8%) patients
      had PC expressed by increased lung uptake of 99mTc- MDP and 28 (57.1%) patients
      had PHT with a mean systolic PAP of 46 +/- 11 mm Hg. No correlation was found
      between PC and PHT. CONCLUSION: The data suggest that PC expressed by lung uptake
      of 99mTc-MDP has no role in the pathogenesis of PHT among ESRD patients
      undergoing HD therapy via A-V access.

PMID- 15253738
TI  - Myocardial scintigraphy using a fatty acid analogue detects coronary artery
      disease in hemodialysis patients.
AB  - BACKGROUND: Coronary artery disease contributes significantly to mortality in end
      stage renal disease (ESRD) patients. Single-photon emission computed tomography
      (SPECT) using an iodinated fatty acid analogue, iodine-123-methyl
      iodophenylpentadecanoic acid (123I-BMIPP), can assess fatty acid metabolism in
      the myocardium. We investigated the ability of 123I-BMIPP SPECT to detect
      coronary artery disease in hemodialysis patients compared with 201thallium
      chloride (201Tl) SPECT. METHODS: We prospectively studied 130 ESRD patients
      undergoing hemodialysis for a mean of 88.6 months (male/female, 77/53; mean age,
      63.8 years). Dual SPECT using 123I-BMIPP and 201Tl was performed, followed by
      coronary angiography. SPECT findings were graded in 17 segments on a five-point
      scale (0, normal uptake; 4, none) and assessed as a summed score. RESULTS: By
      coronary angiography, 71.5% of patients (93/130) had significant coronary
      stenosis (> or =75%), and five patients showed coronary spasm without coronary
      stenosis. When a BMIPP summed score of 6 or more was defined as abnormal,
      sensitivity, specificity, and accuracy for detecting coronary artery disease by
      BMIPP SPECT were 98.0%, 65.6%, and 90.0%, respectively; in contrast, these
      parameters for detecting coronary artery disease by Tl SPECT were 84.7%, 46.9%,
      and 75.0%, respectively, when a Tl summed score of 1 or more was defined as
      abnormal. In receiver operating characteristic analysis, the area under the curve
      was 0.895 in BMIPP and 0.727 in Tl SPECT, respectively. CONCLUSION: Resting BMIPP
      SPECT is superior to Tl SPECT for detecting coronary lesions, and provides safe
      screening for coronary artery disease among maintenance hemodialysis patients.

PMID- 15253739
TI  - Protective effect of vitamin C on 8-hydroxy-2'-deoxyguanosine level in peripheral
      blood lymphocytes of chronic hemodialysis patients.
AB  - BACKGROUND: This study focused on the effect of vitamin C on the 8-hydroxy-2'
      deoxyguanosine (8-OHdG) level of cellular DNA, as well as 8-oxoguanine-DNA
      glycosylase 1 (hOGG1) and human MutT homologue (hMTH1) gene expression in
      peripheral blood lymphocytes of chronic hemodialysis patients. METHODS: Sixty
      chronic hemodialysis patients (35 men and 25 women) were recruited to participate
      in a randomized, placebo-controlled study. Treatment order is block-randomized
      with intravenous sodium ascorbate (vitamin C, 300 mg) or placebo (0.9% saline),
      administered postdialysis three times a week. We evaluated 8-OHdG level,
      intracellular reactive oxygen species (ROS) production, and gene expression of
      hOGG1 and hMTH1 in peripheral blood lymphocytes by using high-performance liquid
      chromatography (HPLC) electrochemical detection method, flow cytometric analysis,
      and reverse transcription-polymerase chain reaction (RT-PCR), respectively.
      RESULTS: A total of 51 patients completed the study (26 in placebo group and 25
      in vitamin C group). Mean 8-OHdG levels significantly decreased in total subjects
      following 8 weeks of vitamin C supplementation (22.9 vs. 18.8/10(6) dG, P <
      0.01). The decrease in 8-OHdG levels after vitamin C supplementation was also
      noted in the patients with ferritin <500 or > or =500 microg/L and transferrin
      saturation (TSAT) <50 or > or =50% (P < 0.05). But 8-OHdG levels had no
      significant changes in total patients or in the four subgroups of patients
      treated with placebo as compared to their baselines. Intracellular ROS production
      by lymphocytes from the four subgroups of patients, either spontaneous (P < 0.05)
      or phorbol-12-myristate-13-acetate (PMA)-stimulated (P < 0.001), was
      significantly reduced after 8 weeks vitamin C supplementation. Steady-state hOGG1
      mRNA levels were significantly up-regulated at 24 hours after vitamin C
      administration (P < 0.05), but hMTH1 mRNA levels were not. The changes in the
      spontaneous and PMA-stimulated ROS production, and an up-regulation of hOGG1 mRNA
      expression were not observed in patients treated with placebo as compared to
      their baselines. CONCLUSION: Vitamin C supplementation in chronic hemodialysis
      patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS
      production, as well as up-regulate hOGG1 gene expression for repair. There is no
      compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte
      DNA base oxidation, even in the status of increased iron stores.

PMID- 15253740
TI  - Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis
      patients.
AB  - BACKGROUND: Renal anemia is an important determinant for left ventricular
      hypertrophy in dialysis patients and an independent prognosis parameter for the
      cardiovascular survival in dialysis patients. In addition, an autonomic
      dysfunction is associated with the uremic state and influences the cardiovascular
      risk in patients with end-stage renal disease (ESRD). METHODS: We investigated in
      this prospective longitudinal study the effect of hemoglobin normalization by a
      chronic treatment with recombinant human erythropoietin (rhEPO) on cardiovascular
      prognosis parameters in 23 patients on chronic hemodialysis with renal anemia
      (hemoglobin concentration < or =10.5 g/dL) and echocardiographically proven left
      ventricular hypertrophy. We studied muscle sympathetic nerve activity measured by
      microneurography; cardiopulmonary baroreflex activity by lower-body negative
      pressure (LBNP-) testing; left ventricular structure and mass index (LVMI) by
      echocardiography; blood pressure by 24-hour readings; peripheral blood flow and
      vascular resistance by plethysmography before (U1) and after 7 months of chronic
      rhEPO treatment (U2). RESULTS: In the anemic state, mean (+/- SD) muscle
      sympathetic nerve activity in ESRD was elevated (U1 rest, 34 +/- 13 bursts per
      minute) and cardiopulmonary baroreflex response during LBNP markedly lacking (U1 
      15 mm Hg, 34 +/- 13 bursts per minute) reflecting a severely impaired autonomic
      function. Normalization of the hemoglobin concentration by chronic rhEPO
      treatment (U1, 10.5 +/- 0.9 g/dL versus U2, 13.4 +/- 3.1 g/dL, P <0.001) did not
      influence sympathetic nerve activity (U2, 34 +/- 15 bursts per minute, NS) and
      cardiopulmonary baroreflex sensitivity did not change (U2 -15 mm Hg, 37 +/- 16
      bursts per minute, NS). LVMI decreased significantly after chronic treatment with
      rhEPO (U1, 134 +/- 26 g/m2 versus U2, 97 +/- 25 g/m2, P < 0.001) and left
      ventricular geometry developed from an asymmetric to a symmetric configuration
      (U1, relative wall thickness 0.58 versus U2, 0.43, P < 0.001). Under treatment
      with rhEPO, 24-hour systolic and diastolic blood pressure did not increase
      (systolic U1, 132 +/- 4 mm Hg versus U2, 128 +/- 3 mm Hg, NS, and diastolic U1,
      76 +/- 2 mm Hg versus U2, 73 +/- 2 mm Hg, NS). Peripheral blood flow (U1, 6.1 +/-
      3.3 mL/100 mL/min versus U2, 6.2 +/- 0.6 mL/100 mL/min, NS) as well as forearm
      vascular resistance (U1, 15.7 +/- 3.3 mm Hg/mL/100 mL versus U2, 14.9 +/- 3.1 mm
      Hg/mL/100 mL, NS) did not change by chronic rhEPO treatment. CONCLUSION:
      Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has
      beneficial cardiovascular effects with regression of left ventricular hypertrophy
      and improvement of left ventricular geometry. However, a reduction of sympathetic
      overactivity or a resetting of baroreceptor sensitivity by a rhEPO treatment in
      dialysis patients in the medium-term could not be demonstrated. The reason for
      this may be the complex and multifactorial pathomechanism of autonomic
      dysfunction and cardiovascular disease in ESRD.

PMID- 15253741
TI  - Intravenous iron administration induces oxidation of serum albumin in
      hemodialysis patients.
AB  - BACKGROUND: Intravenous iron administration (IVIR) is effective for correcting
      anemia in hemodialysis (HD) patients. However, it may also enhance the generation
      of hydroxyl radicals. Recently, plasma proteins have been demonstrated to be
      extremely susceptible to oxidative stress. Therefore, we investigated the effect
      of IVIR on the oxidative status of albumin, a major plasma protein, in HD
      patients. METHODS: Eleven hemodialysis (HD) patients were treated with 40 mg of
      saccharated ferric oxide intravenously after every dialysis session for four
      weeks, and 11 age-/gender-matched HD patients were treated with vehicle. We
      performed high performance liquid chromatography (HPLC) analysis of serum albumin
      and determined the levels of reduced and oxidized albumin. Carbonyl formation of
      plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine
      antibody in patients with or without IVIR. RESULTS: IVIR resulted in an increase
      in both disulfide form (f(HNA-1)) and oxidized form (f(HNA-2)) of albumin in HD
      patients (36.0 +/- 6.03 vs. 41.7 +/- 6.27; 5.46 +/- 1.50 vs. 8.7 +/- 2.22,
      respectively, P < 0.05). The findings here also show that IVIR substantially
      increased plasma protein carbonyl content by oxidizing albumin. In addition, we
      found a strong correlation between plasma carbonyl content and the levels of
      oxidized albumin (f(HNA-1) and f(HNA-2)) in HD patients (R= 0.674 and R= 0.724,
      respectively, P < 0.01). CONCLUSION: The results of this study indicate that the
      HPLC analysis of serum albumin represents a potentially useful method for the
      quantitative and qualitative evaluation of oxidative stress in HD patients, and
      strongly suggest the possibility that oxidative stress, generated by IVIR,
      enhances the oxidation of albumin in those patients.

PMID- 15253742
TI  - Quantification of free water transport in peritoneal dialysis.
AB  - BACKGROUND: In peritoneal dialysis (PD) total net ultrafiltration (NUF) is
      dependent on transport through small pores and through water channels in the
      peritoneum. These channels are impermeable to solutes, and therefore, crystalloid
      osmotic-induced free water transport occurs through them. Several indirect
      methods to assess free water transport have been suggested. The difference in NUF
      between a 3.86% and a 1.36% solution gives a rough indication, but is very time
      consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the
      initial phase of a 3.86% exchange is another way to estimate free water
      transport. In the present study, a method was applied to calculate free water
      transport by calculating sodium-associated water transport in one single 3.86%
      glucose dwell. METHODS: Forty PD patients underwent one standard peritoneal
      permeability analysis (SPA) with a 1.36% glucose solution, and another with a
      3.86% glucose solution. At different time points intraperitoneal volume and
      sodium concentration were assessed. This made it possible to calculate total
      sodium transport. By subtracting this transport (which must have occurred through
      the small pores) from the total fluid transport, free water transport remained.
      These results were compared with the other methods to estimate free water
      transport. RESULTS: For the 1.36% glucose dwell, total transcapillary
      ultrafiltration in the first hour (TCUF(0-60)) was 164 mL, transport through the
      small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86%
      glucose solution, total TCUF(0-60) was 404 mL, transport through the small pores
      was 269 mL, and free water transport was 135 mL (34%). The contribution of free
      water transport in the first minute (TCUF(0-1)) was 39% of the total fluid
      transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF
      <400 mL after 4 hours). For these patients the contribution of free water to
      TCUF(0-1) was significantly lower than for those with normal ultrafiltration (20%
      vs. 48%, P < 0.05). A strong correlation was present between free water transport
      as a percentage of total fluid transport and the maximum dip in D/P sodium (r=
      0.84). The correlation was not significant with the difference in net
      ultrafiltration of 3.86% and 1.36% solutions (r= 0.24, P= 0.3). CONCLUSION: The
      method applied here is the first direct quantification of free water transport,
      calculated from a single standard peritoneal function test. It offers a quick
      possibility to evaluate patients suffering from ultrafiltration failure. In these
      patients free water transport was impaired, but the origin of this impairment is
      still to be determined.

PMID- 15253743
TI  - Global heterogeneity of glomerular volume distribution in early diabetic
      nephropathy.
AB  - BACKGROUND: Morphologic characteristics in early stage of nephropathy of
      noninsulin-dependent diabetes mellitus (NIDDM) have not been determined despite
      the fact thatdiagnosis in this stage of the disease is important for the
      prognosis. We hypothesized that heterogeneity in glomerular volume-distribution
      may be a sensitive index of early stage of diabetic nephropathy in NIDDM.
      METHODS: In spontaneous diabetic rats [Otsuka Long-Evans Tokushima Fatty (OLETF)
      rat (N= 5)] of 27 to 28 weeks, an experimental model of early diabetic
      nephropathy in human NIDDDM and age-matched control rats [Long Evans Tokushima
      Lean (LETO) rat (N= 5)], we completely filled the kidney with contrast medium.
      Glomeruli were visualized as three-dimensional images using x-ray micro-computed
      tomography (micro-CT). Glomerular volumes (N= 400 in each kidney) were directly
      measured and evaluated as absolute volume and normalized values to kidney weight
      and body weight. Scattering of glomerular volume-distribution was evaluated as
      coefficient variation (CV) (SD/mean). RESULTS: The CV was significantly larger in
      OLETF rat (0.195) comparing to LETO rat (0.146, P < 0.01). This difference was
      even consistent under the normalization to kidney weight and body weight.
      Absolute glomerular volume was larger in OLETF rat compared to LETO rat (P <
      0.005); however, when glomerular volume was normalized, this variable was
      comparable between two groups. CONCLUSION: We visualized three-dimensional
      glomerular images in the early stages of diabetic nephropathy using micro-CT and
      quantified the heterogeneity in glomerular volume distribution throughout the
      cortex by direct measurement of the individual. We propose that heterogeneity in
      glomerular volume distribution is a sensitive parameter to ascertain early
      diabetic nephropathy in NIDDM.

PMID- 15253744
TI  - Do kidney tubules serve an angiogenic soup?

PMID- 15253745
TI  - The quest for the gene responsible for medullary cystic kidney disease type 1.

PMID- 15253746
TI  - Effect of obesity on PD versus HD survival: is caloric intake the discriminating
      factor?

PMID- 15253747
TI  - On the epithelial-mesenchymal transition of mesothelial cells.

PMID- 15253748
TI  - A catalog of gene expression in the developing kidney.

PMID- 15253750
TI  - Urea space and body water.

PMID- 15253751
TI  - Is C0 better than C2 as a determinant of rejection in renal transplant
      recipients?

PMID- 15253752
TI  - About the mechanisms of renoprotective effect of angiotensin inhibitors on lupus
      nephritis.

PMID- 15253754
TI  - Actin cytoskeleton in ischemic acute renal failure.

PMID- 15253756
TI  - Fat chance: genetic syndromes with obesity.
AB  - Although obesity shows high heritability, we are aware of only a small number of
      genes that affect adipose mass in humans. Genetic syndromes with obesity
      represent unique opportunities to gain insight into the control of energy
      balance. The majority of obesity syndromes can be distinguished by the presence
      of mental retardation. We performed a systematic search of such syndromes and
      reviewed the literature with a focus on distinguishing clinical features, the
      characteristics of their obesity, and the underlying pathogenetic mechanisms. We
      predict that the study of these conditions will shed light on common forms of
      obesity.

PMID- 15253757
TI  - Fishing for new genes in skin biology: impact of cytogenetics on gene discovery.
AB  - Research into the field of skin biology has grown exponentially over the past two
      decades. Even though the fundamental molecular pathways are still not fully
      understood, there have been significant advances in our understanding of the
      underlying mechanisms involved in the pathogenesis of genodermatosis. The cloning
      of many candidate genes involved in the etiology of skin diseases has been
      facilitated by initial cytogenetic evidence. This review will synthesize recent
      findings that led to the discovery of candidate genes for anhidrotic ectodermal
      dysplasia, Williams-Beuren syndrome, neurofibromatosis-I and tricho-rhino
      phalangeal syndrome.

PMID- 15253761
TI  - Genetic counseling for familial conditions during pregnancy: an analysis of
      patient characteristics.
AB  - Reproductive genetic counseling for a familial genetic risk factor preferably
      takes place before conception. However, of the women with a family history of
      genetic conditions who attend our department of clinical genetics, about 10-20%
      attend for the first time during a pregnancy. The current study aims to explore
      patient-related factors that may affect this late timing of reproductive genetic
      counseling. Consecutive pregnant (n = 100) and non-pregnant (n = 84) women
      visiting the department of clinical genetics for a genetic risk factor which was
      not age related completed a questionnaire immediately prior to the consultation.
      The questionnaire asked for (a) background characteristics, i.e. socio
      demographic, obstetric, and disease characteristics (b) cognitive factors, i.e.
      initiative of referral, knowledge of the risk factor involved, risk perception,
      worry, child wish, attitudes toward abortion, and preferred participation in
      decision making, and (c) reasons for the timing of the consultation and for
      seeking genetic counseling. Pregnant women appeared to be higher educated,
      considered their children more often as healthy and were less often affected
      themselves, as compared to non-pregnant women. They also estimated their chance
      of having an affected child as lower, and they worried less. Furthermore, the
      initiative for referral was taken less often by the pregnant woman herself and
      more often by a medical worker. There were no major differences between the two
      study groups in knowledge, perceived severity of the risk factor, child wish,
      attitudes toward abortion, desired participation in decision making, and reasons
      to seek genetic counseling. Women indicated no specific reasons for their timing
      of referral for reproductive genetic counseling, e.g. during vs before pregnancy.
      Our data suggest that this timing of referral is not influenced predominantly by
      the women's level of knowledge. Rather, women's estimation of genetic risks and
      their degree of worry, which may be in accordance with the actual risk figures,
      seem to play a role in seeking genetic counseling. Although further studies are
      required, a more active role of health care providers seems warranted if we want
      to prevent genetic counseling for familial genetic conditions during pregnancy as
      much as possible.

PMID- 15253762
TI  - Genome-wide screening using automated fluorescent genotyping to detect cryptic
      cytogenetic abnormalities in children with idiopathic syndromic mental
      retardation.
AB  - Mental retardation (MR) is the most common developmental disability, affecting
      approximately 2% of the population. The causes of MR are diverse and poorly
      understood, but chromosomal rearrangements account for 4-28% of cases, and
      duplications/deletions smaller than 5 Mb are known to cause syndromic MR. We have
      previously developed a strategy based on automated fluorescent microsatellite
      genotyping to test for telomere integrity. This strategy detected about 10% of
      cryptic subtelomeric rearrangements in patients with idiopathic syndromic MR.
      Because telomere screening is a first step toward the goal of analyzing the
      entire genome for chromosomal rearrangements in MR, we have extended our strategy
      to 400 markers evenly distributed along the chromosomes to detect interstitial
      anomalies. Among 97 individuals tested, three anomalies were found: two deletions
      (one in three siblings) and one parental disomy. These results emphasize the
      value of a genome-wide microsatellite scan for the detection of interstitial
      aberrations and demonstrate that automated genotyping is a sensitive method that
      not only detects small interstitial rearrangements and their parental origin but
      also provides a unique opportunity to detect uniparental disomies. This study
      will hopefully contribute to the delineation of new contiguous gene syndromes and
      the identification of new imprinted regions.

PMID- 15253763
TI  - Interstitial deletion of 10p and atrial septal defect in DiGeorge 2 syndrome.
AB  - We present molecular genetic investigations of a 4-year-old boy with craniofacial
      dysmorphism and developmental delay. Trivial mitral and tricuspid regurgitation
      without gross structural abnormality was diagnosed by echocardiography. High
      resolution chromosome analysis revealed an interstitial deletion,
      del(10)(p12.1p12.32). To characterize the deletion size and breakpoints, we
      performed fluorescence in situ hybridization analysis using 27 BAC clones. Our
      data demonstrate an approximately 5.5 Mb deletion del(10)(p12.1p12.31).
      Surprisingly, the BAC clone RP11-56H7 that contains NEBL, an apparent downstream
      gene of the cardiogenic transcription factor HAND2 previously shown to be deleted
      in the patients with DiGeorge 2 syndrome and 10p13 deletion, was deleted in our
      patient with 10p12.1-p12.31 deletion. In addition, we provide clinical data and
      results of molecular analysis for a patient with multiple congenital anomalies
      including Ebstein's anomaly, kidney malformations, and 10p13-p14 deletion. We
      also reviewed 19 patients with congenital heart defects and deletions involving
      10p and propose that atrial septal defect (ASD) is a common cardiac anomaly
      associated with DiGeorge 2 syndrome. Based on genotype-phenotype analysis of
      published patients and those reported herein, we propose an approximately 1.0 Mb
      critical region between loci D10S547 and D10S2176 in 10p14 to be associated with
      ASD. Considering that septal defects are the most frequent congenital heart
      anomaly, we suggest that further investigations in the 10p critical region are
      important to identify gene(s) responsible for this common birth defect.

PMID- 15253764
TI  - Putative common origin of two MLH1 mutations in Italian-Quebec hereditary non
      polyposis colorectal cancer families.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common
      inherited cancer syndromes, accounting for 3-5% of all cases of colorectal
      cancer. In most HNPCC families, the disease is caused by a germline mutation in
      MLH1 or MSH2. In some populations, founder mutations appear to explain a
      substantial fraction of HNPCC. We report here the identification and preliminary
      characterization of two putative MLH1 founder mutations. The mutation
      MLH1c.1831delAT was shown to segregate in two Quebec families of Italian origin
      who fulfilled the Amsterdam criteria for HNPCC. Haplotype analysis using five
      intragenic microsatellite/single nucleotide polymorphism markers spanning MLH1 on
      chromosome 3 showed that these two unrelated families share an identical
      haplotype. In addition, two other Italian kindred whose affected members carry
      MLH1g.IVS6 + 3A>G also share a common haplotype, suggesting that, similarly, the
      latter mutation has a common origin. These mutations are the first putative
      founder MLH1 mutations to be identified in HNPCC kindred of Italian origin.

PMID- 15253765
TI  - Novel mutations in the EXT1 gene in two consanguineous families affected with
      multiple hereditary exostoses (familial osteochondromatosis).
AB  - Multiple hereditary exostoses (HME) is an autosomal dominant developmental
      disorder exhibiting multiple osteocartilaginous bone tumors that generally arise
      near the ends of growing long bones. Here, we report two large consanguineous
      families from Pakistan, who display the typical features of HME. Affected
      individuals also show a previously unreported feature--bilateral overriding of
      single toes. Analysis using microsatellite markers for each of the known EXT
      loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation
      analysis of the EXT1 gene revealed that affected individuals were heterozygous
      for an in-frame G-to-C transversion at the conserved splice donor site in intron
      1. This mutation is predicted to disrupt splicing of the first intron and produce
      a frameshift that leads to a premature termination codon. In the second family,
      an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555
      followed by a premature termination, a further 10 codons downstream. In both
      families, an increased number of affected male subjects were observed. In
      affected females in family 2, phenotypic variability and incomplete penetrance
      were noted.

PMID- 15253766
TI  - Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech
      patients with pre-lingual deafness.
AB  - Mutations in the gene gap junction beta 2 (GJB2), the gene for the connexin 26,
      are the most common cause of pre-lingual deafness worldwide. The mutation 35delG
      within GJB2 is prevalent in Europe. To date, there are no data about GJB2
      mutation spectrum and frequencies from the Czech population. We investigated and
      report here the spectrum and frequencies of mutations in the GJB2 gene among 156
      unrelated, congenital deafness Czech patients. Allele-specific polymerase chain
      reaction, together with fluorescent fragment analysis, were used for the
      detection of the 35delG mutation. The entire coding region of the GJB2 was
      directly sequenced in all patients who were not homozygous for the 35delG. No
      pathogenic mutation was detected in 51.9% of patients. At least one pathogenic
      mutation was found in 48.1% of patients, and both pathogenic mutations were
      detected in 37.8% of patients. Single mutations in a heterozygous state were
      detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected
      disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was
      found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of
      pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic
      is 1 : 29.6. Testing for only the three most common mutations would detect over
      96% of all pathogenic alleles in the Czech Republic.

PMID- 15253767
TI  - Enzyme replacement therapy with agalsidase beta improves cardiac involvement in
      Fabry's disease.
AB  - Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency
      of alpha-galactosidase that results in an accumulation of neutral
      glycosphingolipids throughout the body, including the cardiovascular system.
      Fabry cardiomyopathy, characterized by progressive severe concentric left
      ventricular (LV) hypertrophy, is very frequent and is the most important cause of
      death in affected patients. Enzyme replacement therapy (ERT) allows a specific
      treatment for this disease, however, there are very few data on the effectiveness
      of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were
      studied on basal condition and after 6 and 12 months of treatment with algasidase
      beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic
      evaluation was performed in all patients. Interpretable Doppler recordings of
      transmitral flow and pulmonary flow velocity curves were also acquired. At
      baseline, the patients with Fabry's disease had increased LV septum and posterior
      wall thickness, normal LV fractional shortening, LV ejection fraction, normal
      Doppler parameters of mitral inflow but a duration of pulmonary vein flow
      velocity wave exceeding that of the mitral wave at atrial systole. ERT did not
      affect heart rate and arterial pressure. LV internal diameters did not change,
      there was a slight but not significant decrease in the LV posterior wall
      thickening and a progressive decrease in the interventricular septum thickening
      (p < 0.025) and in LV mass (p < 0.001) The difference in duration between
      pulmonary vein flow velocity wave and mitral wave at atrial systole significantly
      decreased (p < 0.001). These results suggest that ERT in patients with Fabry
      cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.

PMID- 15253768
TI  - Detection of CYP3A4*1B and CYP3A4*2 polymorphisms by RFLP. Distribution
      frequencies in a Mexican population.

PMID- 15253770
TI  - Daily rhythm of circulating fat soluble vitamin concentration (A, D, E and K) in
      the horse.
AB  - BACKGROUND: Many physiological processes of mammalian species exhibit daily
      rhythmicity. An intrinsic relationship exists between fat soluble vitamins (A, D,
      E and K) and several body functions. Few investigations on the rhythmic pattern
      of vitamins in domestic animals have been carried out. The present study
      evaluated the circadian rhythmicity of fat soluble vitamins in the horse.
      METHODS: Blood samples from 5 Thoroughbred mares were collected at four-hour
      intervals over a 48-hour period (starting at 8:00 hours on day 1 and finishing at
      4:00 on day 2) via an intravenous cannula inserted into the jugular vein. Fat
      soluble vitamin concentration in the serum (A, D, E and K) was measured by HPLC.
      One-way repeated measures analysis of variance (ANOVA) was used to determine
      significant differences. p values < 0.05 were considered statistically
      significant. RESULTS: ANOVA showed a highly significant effect of time in all the
      horses for the vitamins studied (p < 0.0001). The application of the periodic
      model and the statistical analysis of the "Cosinor" enabled us to define the
      periodic parameters and their acrophases (expressed in hours) during the 2 days
      of monitoring: all the studied vitamins showed diurnal acrophases with values
      between 15:16 and 18:08 hours. CONCLUSION: Fat soluble vitamins exhibit daily
      rhythmicity with diurnal peak. Further investigations could help optimize the use
      of these substances according to their circadian (or other) rhythms.

PMID- 15253769
TI  - Viral and immunological factors associated with breast milk transmission of SIV
      in rhesus macaques.
AB  - BACKGROUND: The viral and host factors involved in transmission of HIV through
      breastfeeding are largely unknown, and intervention strategies are urgently
      needed to protect at-risk populations. To evaluate the viral and immunological
      factors directly related to milk transmission of virus, we have evaluated the
      disease course of Simian Immunodeficiency Virus (SIV) in lactating rhesus
      macaques (Macaca mulatta) as a model of natural breast milk transmission of HIV.
      RESULTS: Fourteen lactating macaques were infected intravenously with
      SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their
      suckling infants throughout the disease course. Transmission was observed in 10
      mother-infant pairs over a one-year period. Two mothers transmitted virus during
      the period of initial viremia 14-21 days post inoculation (p.i.) and were
      classified as early transmitters. Peak viral loads in milk and plasma of early
      transmitters were similar to other animals, however the early transmitters
      subsequently displayed a rapid progressor phenotype and failed to control virus
      expression as well as other animals at 56 days p.i. Eight mothers were classified
      as late transmitters, with infant infection detected at time points in the
      chronic stage of the maternal SIV disease course (81 to 360 days). Plasma viral
      loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late
      transmitters and non-transmitters. Late breast milk transmission, however, was
      correlated with higher average milk viral loads and more persistent viral
      expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four
      mothers failed to transmit virus, despite disease progression and continuous
      lactation. CONCLUSION: These studies validate the SIV-infected rhesus macaque as
      a model for breast milk transmission of HIV. As observed in studies of HIV
      infected women, transmission occurred at time points throughout the period of
      lactation. Transmission during the chronic stage of SIV-infection correlated with
      a threshold level of virus expression as well as more persistent shedding in
      milk. This model will be a valuable resource for deciphering viral and host
      factors responsible for transmission of HIV through breastfeeding.

PMID- 15253771
TI  - Management of osteoporosis.
AB  - Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5
      million fragility fractures per year. The consequences of these fractures include
      pain, disability, depression, loss of independence, and increased mortality. The
      burden to the healthcare system, in terms of cost and resources, is tremendous,
      with an estimated direct annual USA healthcare expenditure of about $17 billion.
      With longer life expectancy and the aging of the baby-boomer generation, the
      number of men and women with osteoporosis or low bone density is expected to rise
      to over 61 million by 2020. Osteoporosis is a silent disease that causes no
      symptoms until a fracture occurs. Any fragility fracture greatly increases the
      risk of future fractures. Most patients with osteoporosis are not being diagnosed
      or treated. Even those with previous fractures, who are at extremely high risk of
      future fractures, are often not being treated. It is preferable to diagnose
      osteoporosis by bone density testing of high risk individuals before the first
      fracture occurs. If osteoporosis or low bone density is identified, evaluation
      for contributing factors should be considered. Patients on long-term
      glucocorticoid therapy are at especially high risk for developing osteoporosis,
      and may sustain fractures at a lower bone density than those not taking
      glucocorticoids. All patients should be counseled on the importance of regular
      weight-bearing exercise and adequate daily intake of calcium and vitamin D.
      Exposure to medications that cause drowsiness or hypotension should be minimized.
      Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture
      should be considered. These include fall prevention through balance training and
      muscle strengthening, removal of fall hazards at home, and wearing hip protectors
      if the risk of falling remains high. Pharmacologic therapy can stabilize or
      increase bone density in most patients, and reduce fracture risk by about 50%. By
      selecting high risk patients for bone density testing it is possible to diagnose
      this disease before the first fracture occurs, and initiate appropriate treatment
      to reduce the risk of future fractures.

PMID- 15253772
TI  - Visualization of elusive structures using intracardiac echocardiography: insights
      from electrophysiology.
AB  - Electrophysiological mapping and ablation techniques are increasingly used to
      diagnose and treat many types of supraventricular and ventricular tachycardias.
      These procedures require an intimate knowledge of intracardiac anatomy and their
      use has led to a renewed interest in visualization of specific structures. This
      has required collaborative efforts from imaging as well as electrophysiology
      experts. Classical imaging techniques may be unable to visualize structures
      involved in arrhythmia mechanisms and therapy. Novel methods, such as
      intracardiac echocardiography and three-dimensional echocardiography, have been
      refined and these technological improvements have opened new perspectives for
      more effective and accurate imaging during electrophysiology procedures.
      Concurrently, visualization of these structures noticeably improved our ability
      to identify intracardiac structures. The aim of this review is to provide
      electrophysiologists with an overview of recent insights into the structure of
      the heart obtained with intracardiac echocardiography and to indicate to the echo
      specialist which structures are potentially important for the
      electrophysiologist.

PMID- 15253773
TI  - Tents pre-treated with insecticide for malaria control in refugee camps: an
      entomological evaluation.
AB  - BACKGROUND: A refugee shelter that is treated with insecticide during manufacture
      would be useful for malaria control at the acute stage of an emergency, when
      logistic problems, poor co-ordination and insecurity limit the options for
      malaria control. METHODS: Tents made of untreated canvas with deltamethrin
      treated polyethylene threads interwoven through the canvas during manufacture,
      'pre-treated tents', were tested in Pakistan for their impact on malaria vectors.
      Fixed-time contact bioassays tested the insecticidal activity of the material
      over 3 months of outdoor weathering. Unweathered tents were erected under large
      trap-nets on outdoor platforms and tested using wild-caught, host-seeking
      mosquitoes and insectary-reared mosquitoes released during the night into the
      trap-nets. RESULTS: The insecticide-treated tents were effective both in killing
      mosquitoes and reducing blood-feeding. Mean 24 hour mortality was 25.7% on
      untreated tents and 50.8% on treated tents (P = 0.001) in wild anophelines and
      5.2% on untreated tents and 80.9% on treated tents (P < 0.001) in insectary
      reared Anopheles stephensi. Blood-feeding of wild anophelines was reduced from
      46% in the presence of an untreated tent to 9.2% (P < 0.001) in the presence of
      treated tents and from 51.1% to 22.2% (P < 0.001) for insectary-reared An.
      stephensi. In contact bioassays on tents weathered for three months there was
      91.3% mortality after 10-minute exposure and a 24 h holding period and 83.0%
      mortality after 3-minute exposure and a 24 h holding period. CONCLUSION: The
      results demonstrate the potential of these pre-treated canvas-polyethylene tents
      for malaria control. Further information on the persistence of the insecticide
      over an extended period of weathering should be gathered. Because the
      epidemiological evidence for the effectiveness of pyrethroid-treated tents for
      malaria control already exists, this technology could be readily adopted as an
      option for malaria control in refugee camps, provided the insecticidal effect is
      shown to be sufficiently persistent.

PMID- 15253775
TI  - Genetic diversity of peanut (Arachis hypogaea L.) and its wild relatives based on
      the analysis of hypervariable regions of the genome.
AB  - BACKGROUND: The genus Arachis is native to a region that includes Central Brazil
      and neighboring countries. Little is known about the genetic variability of the
      Brazilian cultivated peanut (Arachis hypogaea, genome AABB) germplasm collection
      at the DNA level. The understanding of the genetic diversity of cultivated and
      wild species of peanut (Arachis spp.) is essential to develop strategies of
      collection, conservation and use of the germplasm in variety development. The
      identity of the ancestor progenitor species of cultivated peanut has also been of
      great interest. Several species have been suggested as putative AA and BB genome
      donors to allotetraploid A. hypogaea. Microsatellite or SSR (Simple Sequence
      Repeat) markers are co-dominant, multiallelic, and highly polymorphic genetic
      markers, appropriate for genetic diversity studies. Microsatellite markers may
      also, to some extent, support phylogenetic inferences. Here we report the use of
      a set of microsatellite markers, including newly developed ones, for phylogenetic
      inferences and the analysis of genetic variation of accessions of A. hypogea and
      its wild relatives. RESULTS: A total of 67 new microsatellite markers (mainly TTG
      motif) were developed for Arachis. Only three of these markers, however, were
      polymorphic in cultivated peanut. These three new markers plus five other markers
      characterized previously were evaluated for number of alleles per locus and gene
      diversity using 60 accessions of A. hypogaea. Genetic relationships among these
      60 accessions and a sample of 36 wild accessions representative of section
      Arachis were estimated using allelic variation observed in a selected set of 12
      SSR markers. Results showed that the Brazilian peanut germplasm collection has
      considerable levels of genetic diversity detected by SSR markers. Similarity
      groups for A. hypogaea accessions were established, which is a useful criteria
      for selecting parental plants for crop improvement. Microsatellite marker
      transferability was up to 76% for species of the section Arachis, but only 45%
      for species from the other eight Arachis sections tested. A new marker (Ah-041)
      presented a 100% transferability and could be used to classify the peanut
      accessions in AA and non-AA genome carriers. CONCLUSION: The level of
      polymorphism observed among accessions of A. hypogaea analyzed with newly
      developed microsatellite markers was low, corroborating the accumulated data
      which show that cultivated peanut presents a relatively reduced variation at the
      DNA level. A selected panel of SSR markers allowed the classification of A.
      hypogaea accessions into two major groups. The identification of similarity
      groups will be useful for the selection of parental plants to be used in breeding
      programs. Marker transferability is relatively high between accessions of section
      Arachis. The possibility of using microsatellite markers developed for one
      species in genetic evaluation of other species greatly reduces the cost of the
      analysis, since the development of microsatellite markers is still expensive and
      time consuming. The SSR markers developed in this study could be very useful for
      genetic analysis of wild species of Arachis, including comparative genome
      mapping, population genetic structure and phylogenetic inferences among species.

PMID- 15253774
TI  - Gametocytogenesis: the puberty of Plasmodium falciparum.
AB  - The protozoan Plasmodium falciparum has a complex life cycle in which asexual
      multiplication in the vertebrate host alternates with an obligate sexual
      reproduction in the anopheline mosquito. Apart from the apparent recombination
      advantages conferred by sex, P. falciparum has evolved a remarkable biology and
      adaptive phenotypes to insure its transmission despite the dangers of sex. This
      review mainly focuses on the current knowledge on commitment to sexual
      development, gametocytogenesis and the evolutionary significance of various
      aspects of gametocyte biology. It goes further than pure biology to look at the
      strategies used to improve successful transmission. Although gametocytes are
      inevitable stages for transmission and provide a potential target to fight
      malaria, they have received less attention than the pathogenic asexual stages.
      There is a need for research on gametocytes, which are a fascinating stage,
      responsible to a large extent for the success of P. falciparum.

PMID- 15253776
TI  - Base-By-Base: single nucleotide-level analysis of whole viral genome alignments.
AB  - BACKGROUND: With ever increasing numbers of closely related virus genomes being
      sequenced, it has become desirable to be able to compare two genomes at a level
      more detailed than gene content because two strains of an organism may share the
      same set of predicted genes but still differ in their pathogenicity profiles. For
      example, detailed comparison of multiple isolates of the smallpox virus genome
      (each approximately 200 kb, with 200 genes) is not feasible without new
      bioinformatics tools. RESULTS: A software package, Base-By-Base, has been
      developed that provides visualization tools to enable researchers to 1) rapidly
      identify and correct alignment errors in large, multiple genome alignments; and
      2) generate tabular and graphical output of differences between the genomes at
      the nucleotide level. Base-By-Base uses detailed annotation information about the
      aligned genomes and can list each predicted gene with nucleotide differences,
      display whether variations occur within promoter regions or coding regions and
      whether these changes result in amino acid substitutions. Base-By-Base can
      connect to our mySQL database (Virus Orthologous Clusters; VOCs) to retrieve
      detailed annotation information about the aligned genomes or use information from
      text files. CONCLUSION: Base-By-Base enables users to quickly and easily compare
      large viral genomes; it highlights small differences that may be responsible for
      important phenotypic differences such as virulence. It is available via the
      Internet using Java Web Start and runs on Macintosh, PC and Linux operating
      systems with the Java 1.4 virtual machine.

PMID- 15253779
TI  - HALS devices and operating room set-up: pearls and pitfalls.
AB  - Although some surgeons maintain that such devices are not necessary, most prefer
      a hand-assist device for the performance of hand-assisted laparoscopy. The three
      devices now available are the Gelport, LapDisc, and Omniport. None is perfect,
      and the choice depends in part on surgeon preference and patient body habitus.
      Each has advantages and disadvantages, and there is room for improvement,
      especially in the ease of hand removal and reinsertion, sturdiness and
      reliability, and ability to maintain the pneumoperitoneum. Beginning laparoscopic
      surgeons are advised to try all three devices and formulate their own opinions.
      As important as the hand-assist device is the operating room set-up. The authors
      provide a checklist covering the imaging system, insufflation equipment,
      hemostatic generators, and instrumentation.

PMID- 15253780
TI  - Trocar arrangement for HALS.
AB  - The appropriate position of the hand-access device and trocars for hand-assisted
      laparoscopic surgery depends on several factors, including the surgeon's
      preference, physical stature, and handedness; the patient's anatomy; and the type
      of procedure being performed. This article reviews the options, including
      measures for special circumstances such as patient obesity.

PMID- 15253781
TI  - Selection of patients for hand-assisted laparoscopic surgery.
AB  - Each of the well-established approaches to laparoscopy-standard transperitoneal,
      standard retroperitoneal, and transperitoneal hand-assisted-has its advantages
      and disadvantages. In order to maximize efficiency and patient benefit, each
      approach should be used selectively. This paper offers recommendations for the
      selective use of the hand-assisted technique, which is particularly useful when
      intact specimen removal is required, the surgeon has limited experience, the
      situation is expected to be difficult (e.g., prior surgery, fibrosis,
      inflammation), or the patient's other medical comorbidities mandate a rapid
      procedure.

PMID- 15253782
TI  - Hand-assisted laparoscopic approach to simple nephrectomy.
AB  - Laparoscopic nephrectomy is commonly employed today for both malignant and benign
      renal conditions, yet the learning curve for all but the simplest procedures
      remains quite steep. Hand-assisted laparoscopic nephrectomy (HALN) bridges the
      gap between standard laparoscopy and open surgery, allowing urologists to develop
      laparoscopic skills while offering the advantages of minimally invasive surgery.
      Simple laparoscopic nephrectomy, performed for benign disorders, can at times
      prove to be challenging because of inflammation around the renal hilum.
      Meticulous dissection during HALN utilizing the intra-abdominal hand for tactile
      feedback, retraction, and blunt dissection may improve one's capabilities
      compared with the standard laparoscopic approach.

PMID- 15253783
TI  - Hand-assisted laparoscopic radical nephrectomy.
AB  - Laparoscopic radical nephrectomy is the new standard of care for localized renal
      cancer. Hand assistance makes the procedure less daunting by providing tactile
      feedback. The authors consider the indications, contraindications, and technique
      for this operation, which provides the patient with the benefits of minimally
      invasive surgery while shortening the learning curve for the surgeon and allowing
      experienced laparoscopists to carry out more complex and challenging operations.

PMID- 15253784
TI  - Hand-assisted laparoscopic partial nephrectomy.
AB  - The resurgence of nephron-sparing surgery for selected renal masses has fueled
      interest in minimally invasive approaches. Several authors have shown that
      laparoscopic partial nephrectomy is feasible if two goals are met: resection of
      the mass with negative margins and control of bleeding. The latter is a
      particular challenge, but numerous options are available. The authors describe
      the operative technique and the available results of hand-assisted laparoscopic
      partial nephrectomy.

PMID- 15253785
TI  - Hand-assisted laparoscopic nephroureterectomy for upper urinary-tract
      transitional-cell carcinoma.
AB  - Hand-assisted laparoscopic nephroureterectomy with laparoscopic, cystoscopic, or
      open management of the distal ureter and bladder cuff allow anyone from the
      novice to the advanced laparoscopic surgeon to perform en-bloc resection of the
      kidney, ureter, and bladder cuff without compromising oncologic principles.
      Patients receive significant benefits in the form of less pain, shorter hospital
      stay, and rapid convalescence. As more urologic surgeons develop skills with this
      procedure, a more critical analysis of early and long-term results will be
      possible. As operative times decrease, hand-assisted laparoscopic
      nephroureterectomy may become the procedure of choice for upper-tract
      transitional-cell carcinoma. The techniques and early results are described.

PMID- 15253786
TI  - Donor nephrectomy in the era of hand-assisted laparoscopic urologic surgery.
AB  - Living-donor nephrectomy has traditionally been performed through a flank
      incision with or without rib resection or by an anterior extraperitoneal
      incision, both of which reduce the willingness of potential donors to undergo the
      procedure. The first successful human laparoscopic donor nephrectomy was reported
      in 1995. In order to reduce warm ischemia and operative time and to make the
      operation safer and easier, some laparoscopic surgeons have used hand assistance.
      The authors describe their technique for this operation and review the results.

PMID- 15253787
TI  - Hand-assisted retroperitoneoscopic radical nephrectomy and nephroureterectomy.
AB  - In laparoscopic operations for renal tumor and upper urinary-tract transitional
      cell carcinoma (TCC), three approaches - the transperitoneal, retroperitoneal,
      and transperitoneal hand-assisted - have been reported. We have performed hand
      assisted retroperitoneoscopic radical nephrectomy (RN) since 1999 and
      nephroureterectomy (NU) since 2000. The surgical techniques and the operative
      results of 95 cases of RN and 54 cases of NU are described and analyzed. These
      procedures were effective and safe for renal tumors and upper urinary-tract TCC.

PMID- 15253788
TI  - Hand-assisted laparoscopic suturing: reconstruction.
AB  - Reconstructive techniques performed using open, laparoscopic, or hand-assisted
      techniques depend on the surgeon's ability to approximate tissues and secure
      bleeding vessels safely and efficiently. The indications for hand-assisted
      suturing include hemostasis, diaphragmatic and visceral repair, and
      reconstruction. The equipment required includes a standard laparoscopic needle
      driver, sutures with noncutting needles, and the handaccess device. The surgeon
      should be comfortable with the particular equipment available in his/her
      operating room. Techniques for suturing during hand-assisted laparoscopic
      reconstructive surgery are described.

PMID- 15253789
TI  - Hand-assisted laparoscopy for multiple organ removal.
AB  - Simultaneous removal of multiple organs is a situation seldom encountered by the
      urologist but may be needed in patients with adult polycystic kidney disease or
      malignancies or infectious processes involving more than one organ. Historically,
      open surgery has been considered necessary to gain adequate exposure. However,
      hand-assisted laparoscopic surgery is suitable for many of these patients. The
      hand-port and trocar positions are chosen according to the laparoscopic
      experience of the surgeon and depend on whether an ambidextrous or nondominant
      hand procedure is planned. Several techniques are described, with a focus on
      bilateral nephrectomy.

PMID- 15253790
TI  - Hand-assisted laparoscopic nephrectomy in autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND: Among patients with renal insufficiency secondary to autosomal
      dominant polycystic kidney disease (ADPKD), the onset of refractory urinary
      infection, hypertension, pain, or hematuria often necessitates a nephrectomy.
      However, the huge size of these kidneys makes a standard laparoscopic approach
      difficult, and the increased fragility of these patients makes an open
      nephrectomy risky. A compromise position has been found in the realm of hand
      assisted laparoscopic techniques, especially for patients in need of a bilateral
      nephrectomy. TECHNIQUE: Hand-assisted laparoscopic nephrectomy (HALN) is
      performed via a hand-assist device placed in the midline. A subxiphoid midline
      port and a midclavicular subcostal port are placed on the ipsilateral side. The
      right hand is inserted for left nephrectomy and the left hand for a right
      nephrectomy. The laparoscope is introduced into the subxiphoid port, and the
      surgeon's primary working instrument is passed via the midclavicular port.
      Occasionally, it is helpful to place a 5-mm subcostal port in the midaxillary
      line to aid in retracting the kidney. Once the kidney is devascularized, it is
      removed via the 7- to 8-cm hand-assist incision; drainage of cysts may be
      necessary during extraction to reduce the kidney size so that it can be
      withdrawn. If a bilateral approach is to be done, then after the first
      nephrectomy, the lateral 5-mm port is closed, and the table is rolled such that
      the contralateral side is elevated about 30 degrees to 45 degrees; a subcostal
      midclavicular 12-mm port is placed, and, if needed, a 5-mm port is inserted
      subcostally in the midaxillary line for renal retraction. RESULTS: Seven
      bilateral hand-assisted laparoscopic nephrectomy cases have been reported. In two
      reports, the mean operating times were 4.8 and 5.5 hours. The mean estimated
      blood loss was <350 mL. CONCLUSION: The hand-assisted laparoscopic approach makes
      both unilateral and bilateral nephrectomy feasible in ADPKD patients with
      acceptable morbidity.

PMID- 15253791
TI  - Hand-assisted laparoscopic cystoprostatectomy and urinary diversion.
AB  - PURPOSE: We report the first series of patients who have undergone hand-assisted
      laparoscopic cystoprostatectomy and diversion (HALCD). PATIENTS AND METHODS:
      Seven patients with muscle-invasive bladder cancer elected to have their surgery
      by hand-assisted laparoscopy. The bladder was excised using a hand-assisted
      laparoscopic technique, and the ileal conduit was constructed through the midline
      incision created for the hand. RESULTS: The operative time was relatively short
      (mean 7.6 hours), blood loss was low (420 mL), and the postoperative stay was
      short (4.6 days). Long-term follow-up is pending. CONCLUSION: Laparoscopic
      techniques for radical cystectomy are currently being explored at several major
      medical centers. Hand-assisted laparoscopy offers the distinct advantages of
      palpation, retraction, speed, and minimal morbidity.

PMID- 15253792
TI  - Complications of hand-assisted laparoscopic urologic surgery.
AB  - Since the first urologic case was reported in 1997, hand-assisted laparoscopic
      surgery (HALS) has proven to be useful for both the experienced and the
      inexperienced laparoscopic surgeon. In a recent series of 196 cases at three
      major medical institutions, 18 patients (9.2%) suffered 32 major complications,
      and 28 patients (14.3%) had 31 minor complications. The most common major
      complications were small-bowel injury, requirement for open conversion to control
      bleeding, and need for reintubation. The most frequent minor complications were
      urinary retention, splenic capsular injury, and prolonged ileus. The author
      discusses ways of recognizing and managing the complications of HALS, including
      physiologic, access-related, intraoperative, and post-operative problems.

PMID- 15253793
TI  - Increase in apparent diffusion coefficient in normal appearing white matter
      following human traumatic brain injury correlates with injury severity.
AB  - Following diffuse traumatic brain injury, there may be persistent functional or
      psychological deficits despite the presence of normal conventional MR images.
      Previous experimental animal and human studies have shown diffusion abnormalities
      following focal brain injury. Our aim was to quantify changes in apparent
      diffusion coefficient (ADC) and absolute relaxation times of normal appearing
      white matter (NAWM) in humans following traumatic brain injury. Twenty-three
      patients admitted with a diagnosis of head injury (nine mild, eight moderate, and
      six severe) were scanned an average of 7.6 days after injury using a quantitative
      echo planar imaging acquisition to obtain co-registered T1, T2, and ADC
      parametric maps. Mean NAWM values were compared with a control group (n = 13).
      The patient group showed a small but significant increase in ADC in NAWM, with no
      significant change in T1 or T2 relaxation times. There was a correlation between
      injury severity and increasing ADC (p = 0.03) but no correlation with either T1
      or T2, suggesting that ADC is a sensitive and independent marker of diffuse white
      matter tissue damage following traumatic insult. None of the patients had a
      reduced ADC, making ischaemia unlikely in this cohort. Pathophysiological
      mechanisms that may explain diffusely raised ADC include vasogenic edema, chronic
      ischemic phenomena, or changes in tissue cytoarchitecture or neurofilament
      alignment.

PMID- 15253794
TI  - Centrifugal distribution of regional cerebral blood flow and its time course in
      traumatic intracerebral hematomas.
AB  - Cerebral blood flow (CBF) alterations following post-traumatic contusions have
      been demonstrated in recent papers. We evaluated regional CBF (rCBF) by means of
      Xenon-enhanced computerized tomography (Xe-CT) in 29 traumatic intracerebral
      hematomas, from 22 patients with severe head injury (GCS < or = 8). Fifty
      traumatic hematoma/Xe-CT CBF measurements were obtained from 39 Xe-CT studies
      performed during the acute phase (corresponding to the first 20 days post
      injury). The rCBF was measured in three different regions of interest: the
      hemorrhagic core, the perihematoma edematous low-density area, and a 1-cm rim of
      perihematoma normal-appearing brain tissue, surrounding the edematous low-density
      area. We found a centrifugal improvement of rCBF as well as a decrease in the
      rates of CBF levels below 18 mL/100 g/min from the core to the periphery (p <
      0.0001), which persisted over time. Ischemic rCBF values were detected in the
      perihematoma low-density area only in 24% of the traumatic hematomas. The time
      course of rCBF levels showed a reduced flow in the first 24 h, with a recovery of
      flow from day 2 to day 4, followed by another reduced flow (p < or = 0.0001) both
      in the perihematoma edematous low-density area and in the non-lesioned tissue.
      Our findings suggest that the only area with persistent ischemic values was the
      hemorrhagic core. Low rCBF levels seen in the perihematoma low-density area may
      only be ascribed partially to ischemia and can possibly recover over time. These
      results could encourage a surgical approach based on an early evacuation of the
      hemorrhagic core associated to a preservation of the surrounding edematous
      tissue.

PMID- 15253795
TI  - Lipid peroxidation early after brain injury.
AB  - The role of lipid peroxidation after brain injury is still not completely
      understood, and results of different studies have been equivocal. In this study,
      three proposed peroxidation markers were determined in patients early after
      isolated head injury and results compared to healthy controls. Malondialdehyde
      (MDA) and thiobarbituric acid-reactive substances (TBARS) were measured in
      plasma, and n-pentane was determined in patients' exhaled air. For MDA and TBARS
      no significant differences could be shown (0.267 vs. 0.358 ng/mL, and 0.896 vs.
      0.814 ng/mL in patients vs. healthy volunteers, respectively). n-Pentane,
      however, was significantly increased in the expired air of patients (0.471 vs.
      0.118 nmol/L in healthy volunteers). Similar results for n-pentane were obtained
      when only male patients and volunteers were considered (0.510 vs. 0.113 nmol/L).
      Stratification according to clinical outcome showed significantly higher values
      for n-pentane in male patients with poor outcome (0.656 nmol/L) in comparison
      with healthy male volunteers (0.113 nmol/L). No difference was found when
      patients were stratified according to the presence or absence of subarachnoid
      hemorrhage. It is concluded that, only in a sub-population of patients with brain
      injury, lipid-peroxidation is a crucial mechanism. n-Pentane seems to be a
      valuable marker to detect lipid peroxidation early after brain trauma.
      Malondialdehyde may be of value only later in the course of the disease. TBARS
      are not a specific marker and should therefore not be used.

PMID- 15253796
TI  - Extracellular Brain pH and Outcome following Severe Traumatic Brain Injury.
AB  - The ability to measure brain tissue chemistry has led to valuable information
      regarding pathophysiological changes in patients with traumatic brain injury
      (TBI). Over the last few years, the focus has been on monitoring changes in brain
      tissue oxygen to determine thresholds of ischemia that affect outcome. However,
      the variability of this measurement suggests that it may not be a robust method.
      We have therefore investigated the relationship of brain tissue pH (pH(b)) and
      outcome in patients with TBI. We retrospectively analyzed prospectively collected
      data of 38 patients admitted to the Neurosciences Critical Care Unit with TBI
      between 1998 and 2003, and who had a multiparameter tissue gas sensor inserted
      into the brain. All patients were managed using an evidence-based protocol
      targeting CPP > 70 mm Hg. Physiological variables were averaged over 4 min and
      analyzed using a generalized least squares random effects model to determine the
      temporal profile of pH(b) and its association with outcome. Median (IQR) minimum
      pH(b) was 7.00 (6.89, 7.08), median (IQR) maximum pH(b) was 7.25 (7.18, 7.33),
      and median (IQR) patient averaged pH(b) was 7.13 (7.07, 7.17). pH(b) was
      significantly lower in those who did not survive their hospital stay compared to
      those that survived. In addition, those with unfavorable neurological outcome had
      lower pH(b) values than those with favorable neurological outcome. pH(b)
      differentiated between survivors and non-survivors. Measurement of pH(b) may be a
      useful indicator of outcome in patients with TBI.

PMID- 15253797
TI  - Occurrence of pituitary dysfunction following traumatic brain injury.
AB  - Traumatic brain injury (TBI) may be associated with impairment of pituitary
      hormone secretion, which may contribute to long-term physical, cognitive, and
      psychological disability. We studied the occurrence and risk factors of pituitary
      dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age
      37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with
      TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and
      neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16
      patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome
      Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good
      recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times
      variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in
      7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%),
      and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and
      posterior pituitary function. Seven patients showed low insulin-like growth
      factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing
      indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with
      GHD were older (p <0.05) than patients with normal GH secretion. Magnetic
      resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether
      pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%)
      showed a combination of multiple abnormalities. Occurrence of pituitary
      dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and
      severe TBI, respectively. GCS scores were significantly (p <0.02) lower in
      patients with pituitary dysfunction compared to those with normal pituitary
      function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between
      pituitary dysfunction and years since TBI, type of injury, and outcome from TBI.
      In conclusion, subjects with a history of TBI frequently develop pituitary
      dysfunction, especially GHD. Therefore, evaluation of pituitary hormone
      secretion, including GH, should be included in the long-term follow-up of all TBI
      patients so that adequate hormone replacement therapy may be administered.

PMID- 15253798
TI  - Lesional expression of RhoA and RhoB following traumatic brain injury in humans.
AB  - Inhibition of the small GTPase Rho or of its downstream target Rho-associated
      kinase (ROCK) has been shown to promote axon regeneration and to improve
      functional recovery following traumatic CNS lesions in the adult rat. In order to
      determine the expression pattern of RhoA and RhoB following human traumatic brain
      injury (TBI) and to assess whether Rho is a possible target for pharmacological
      intervention in humans, we investigated expression patterns of RhoA and RhoB in
      brain specimens from 25 patients who died after closed TBI in comparison to brain
      tissue derived from four neuropathologically unaffected control patients by
      immunohistochemistry. A highly significant lesional upregulation of both RhoA and
      RhoB was observed beginning several hours after the traumatic event and
      continuing for months after TBI. The cellular sources of both molecules included
      polymorphonuclear granulocytes, monocytes/macrophages, and reactive astrocytes.
      Additionally, expression of RhoA was also detected in neuronal cells in some of
      the cases. From our data, we conclude that inhibition of Rho is a promising
      mechanism for the development of new pharmacological interventions in human TBI.
      As the observed upregulation of RhoA and RhoB was still detectable months after
      TBI, we speculate that even delayed treatment with Rho inhibitors might be a
      therapeutic option.

PMID- 15253799
TI  - Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat
      brain.
AB  - Previous studies have demonstrated that traumatic brain injury (TBI) increases
      the vulnerability of the brain to an acute episode of hypoxia-ischemia. The
      objective of the present study was to determine whether TBI alters the
      vulnerability of the brain to a delayed episode of ischemia and, if so, to
      identify contributing mechanisms. Sprague-Dawley rats were subjected to lateral
      fluid-percussion (FP) brain injury (n = 14) of moderate severity (2.3-2.5 atm),
      or sham-injury (n = 12). After recovery for 24 h, all animals underwent an 8-min
      episode of forebrain ischemia, followed by survival for 6 days. Ischemic damage
      in the hippocampus and cerebral cortex of the FP-injured hemisphere was compared
      to that in the contralateral hemisphere and to that in sham-injured animals.
      Remarkably, the number of surviving CA(1) neurons in the middle and lateral
      segments of the hippocampus in the FP-injured hemisphere was significantly
      greater than that in the contralateral hemisphere and sham-injured animals (p <
      0.05). Likewise, in the cerebral cortex the number of damaged neurons tended to
      be lower in the FP-injured hemisphere than in the contralateral hemisphere. These
      results suggest that TBI decreased the vulnerability of the brain to a delayed
      episode of ischemia. To determine whether TBI triggers protective metabolic
      alterations, glycogen levels were measured in cerebral cortex and hippocampus in
      additional animals 24 h after FP-injury (n = 13) or sham-injury (n = 7). Cortical
      glycogen levels in the ipsilateral hemisphere increased to 12.9 +/- 6.4 mmol/kg
      (mean +/- SD), compared to 6.4 +/- 1.8 mmol/kg in the opposite hemisphere and 5.7
      +/- 1.3 mmol/kg in sham-injured animals (p < 0.001). Similarly, in the
      hippocampus glycogen levels in the FP-injured hemisphere increased to 13.4 +/-
      4.9 mmol/kg, compared to 8.1 +/- 2.4 mmol/kg in the contralateral hemisphere (p <
      0.004) and 6.2 +/- 1.5 mmol/kg in sham-injured animals (p < 0.001). These results
      demonstrate that TBI triggers a marked accumulation of glycogen that may protect
      the brain during ischemia by serving as an endogenous source of metabolic energy.

PMID- 15253800
TI  - Mechanical injury modulates AMPA receptor kinetics via an NMDA receptor-dependent
      pathway.
AB  - Alterations in glutamatergic transmission are thought to contribute to secondary
      neuronal damage following traumatic brain injury. Using an in vitro cell injury
      model, we previously demonstrated an apparent reduction in AMPA receptor
      desensitization and resultant potentiation of AMPA-evoked currents after stretch
      injury of cultured neonatal rat cortical neurons. In the present study, we sought
      to further characterize injury-induced enhancement of AMPA current and elucidate
      the mechanisms responsible for this pathological process. Using the patch-clamp
      technique, agonist-activated currents were recorded from control and injured
      neurons. Potentiation of AMPA-mediated currents occurred quickly, within 15-30
      min following injury, and persisted for at least 24 h. Stretch-injury slowed the
      activation and desensitization of AMPA mediated currents recorded from excised
      outside-out patches. The co-application of 100 microM AMPA and 20 microM
      thiocyanate enhanced AMPA receptor desensitization in control neurons and
      restored desensitization in injured neurons. The potentiation of AMPA-elicited
      current was prevented by the NMDA receptor antagonist D-APV (20 microM) or the
      CaMKII inhibitor KN93 (10 microM). These results suggest that mechanical injury
      initiates a biochemical cascade that involves NMDA receptor and CaMKII activation
      and produces a long-lasting reduction of AMPA receptor desensitization, which may
      contribute to the pathophysiology of traumatic brain injury.

PMID- 15253801
TI  - Identification of brain tissue necrosis by MRI: validation by histomorphometry.
AB  - The volume of an experimental necrotic lesion of the cortex expands up to 400% of
      its initial size within the first 24 h after the insult. Lesion expansion, a
      clinically well known phenomenon, is often accompanied by perifocal brain edema
      and consequently difficult to image and to analyze by magnetic resonance imaging
      (MRI). Therefore we aimed to validate a T(2)-weighted spin echo sequence upon its
      ability to distinguish necrotic from edematous brain tissue. Male Sprague-Dawley
      rats (n = 5 per group) were subjected to a cortical freezing lesion leading to
      immediate tissue necrosis with subsequent perifocal vasogenic brain edema.
      Immediately and 4, 12, and 24 h after the lesion the maximal area of necrosis was
      quantified longitudinally by coronal T(2)-weighted spin echo MRI-scans. After the
      last scan, animals were sacrificed for direct comparison of the lesion area
      obtained by MRI and histomorphometry. In parallel groups of animals, lesion
      expansion was quantified by histology. The acquired T(2)-maps clearly distinguish
      the cortical necrosis from perifocal edema and healthy brain. Focal freezing led
      to a cortical lesion of 5.24 +/- 0.36 mm(2) immediately after trauma (0 h; 100%)
      which expanded progressively to a maximum of 6.82 +/- 0.34 mm(2) after 24 h
      (131%; *p < 0.01 vs. 0 h). Lesion expansion quantified by histology was almost
      identical (132% within 24 h). Histological assessment resulted in smaller
      absolute lesion areas compared to MRI, most likely due to shrinking during tissue
      processing (4.72 +/- 0.26 mm(2) vs. 6.82 +/- 0.34 mm(2), p < 0.01). The current
      study shows that necrotic brain tissue can be distinguished from surrounding
      brain edema by T(2)-mapping. The technique is sensitive enough to detect small
      changes in necrosis expansion in vivo as validated by histology. The presented
      technique may be a useful future tool for the non-invasive identification of
      necrotic brain tissue following brain injury (e. g., from trauma or ischemia).

PMID- 15253802
TI  - A mouse model for evaluation of capillary perfusion, microvascular permeability,
      cortical blood flow, and cortical edema in the traumatized brain.
AB  - Genetically engineered mice have successfully been used to investigate molecular
      and cellular mechanisms associated with cell dysfunction following brain trauma.
      Such animals may also offer a possibility to investigate mechanisms involved in
      posttraumatic hemodynamic alterations. The objective of the study was to
      establish a mouse model in which important hemodynamic alterations following
      trauma could be analyzed. C57/BL6 male mice were subjected to controlled cortical
      impact injury (CCI) or sham-injury. Distribution of blood flow was estimated by
      determining number of perfused capillaries using FITC-dextran as an intravascular
      marker. Cortical blood flow was measured using [(14)C]-iodoantipyrine, brain
      water content (BWC) was measured using a wet vs. dry weight method, and
      permeability surface area product (PS) was estimated by the transfer constant for
      [(51)Cr]-EDTA. Number of perfused capillaries in the contusion area was
      progressively reduced during the first 24 h following trauma by at most 60%
      relative to a value of 329 +/- 61/mm(2) in sham-injured animals. Blood flow in
      the contusion area decreased simultaneously by at most 50% relative to a control
      value of 1.8 +/- 0.4 mL.min(-1).g(-1), and was reduced further in subregions
      within the contusion area. BWC in the injured hemisphere increased from 79.3 +/-
      0.5% at control to at most 79.9 +/- 0.6% at 24 h post trauma. PS in the injured
      hemisphere increased by 71% at 3 h post trauma relative to a control value of
      0.45 +/- 0.1 microL.min(-1).g(-1), and was close to control at 24 h. The present
      study demonstrates that brain trauma in addition to a reduction in cortical blood
      flow, reduces number of perfused capillaries, which most likely affects exchange
      of nutrients and fluid. The CCI in mouse is likely to be a useful tool to
      elucidate mechanisms involved in hemodynamic alterations following brain trauma.

PMID- 15253803
TI  - The role of excitotoxicity in secondary mechanisms of spinal cord injury: a
      review with an emphasis on the implications for white matter degeneration.
AB  - Following an initial impact after spinal cord injury (SCI), there is a cascade of
      downstream events termed 'secondary injury', which culminate in progressive
      degenerative events in the spinal cord. These secondary injury mechanisms
      include, but are not limited to, ischemia, inflammation, free radical-induced
      cell death, glutamate excitotoxicity, cytoskeletal degradation and induction of
      extrinsic and intrinsic apoptotic pathways. There is emerging evidence that
      glutamate excitotoxicity plays a key role not only in neuronal cell death but
      also in delayed posttraumatic spinal cord white matter degeneration. Importantly
      however, the differences in cellular composition and expression of specific types
      of glutamate receptors in grey versus white matter require a compartmentalized
      approach to understand the mechanisms of secondary injury after SCI. This review
      examines mechanisms of secondary white matter injury with particular emphasis on
      glutamate excitotoxicity and the potential link of this mechanism to apoptosis.
      Recent studies have provided new insights into the mechanisms of glutamate
      release and its potential targets, as well as the downstream pathways associated
      with glutamate receptor activation in specific types of cells. Evidence from
      molecular and functional expression of glutamatergic AMPA receptors in white
      matter glia (and possibly axons), the protective effects of AMPA/kainate
      antagonists in posttraumatic white matter axonal function, and the vulnerability
      of oligodendrocytes to excitotoxic cell death suggest that glutamate
      excitotoxicity is associated with oligodendrocyte apoptosis. The latter mechanism
      appears key to glutamatergic white matter degeneration after SCI and may
      represent an attractive therapeutic target.

PMID- 15253804
TI  - Combined demyelination plus Schwann cell transplantation therapy increases spread
      of cells and axonal regeneration following contusion injury.
AB  - Several cell populations have been shown to provide a permissive environment for
      axonal extension following transplantation to injury sites. The limited spread of
      transplanted cells from implantation sites in the mature CNS, and the superior
      substrate and trophic environment that they provide, likely contribute to the
      fact that few transplantation-based therapies have elicited axonal extension
      beyond the transplant. The aim of this study was to determine whether (1) regions
      of demyelination cranial and caudal to a spinal cord injury site would improve
      the spread of Schwann cells transplanted into the site of injury, and (2) whether
      this combination therapy was associated with improved anatomical regeneration.
      Three days following contusion injury, anti-galactocerebroside antibodies plus
      complement proteins were injected into the dorsal column cranial and caudal to
      the injury site, resulting in complete and well defined regions of demyelination
      that extended 8 mm either side of the injury site. One day later, naive Schwann
      cells in suspension were injected into the contusion site. Transplanted Schwann
      cells homogeneously redistributed throughout the contusion site and the adjacent
      regions of demyelination cranial and caudal to the contusion site, providing a
      long-distance prospective path for repair that was free of myelin and contained
      transplanted cells. Animals that received demyelination plus transplantation
      therapy, but not untreated or single-treatment groups, exhibited robust axonal
      regeneration beyond the contusion site within the treated dorsal column. Axonal
      regeneration in these animals was not associated with an improvement in locomotor
      ability. These findings suggest that this combination therapy may overcome a
      central limitation of transplant strategies in which the permissive environment
      provided remains at the implantation site.

PMID- 15253805
TI  - Synthetic hydrogel guidance channels facilitate regeneration of adult rat
      brainstem motor axons after complete spinal cord transection.
AB  - Synthetic guidance channels or tubes have been shown to promote axonal
      regeneration within the spinal cord from brainstem motor nuclei with the
      inclusion of agents such as matrices, cells, or growth factors to the tube. We
      examined the biocompatibility and regenerative capacity of synthetic hydrogel
      tubular devices that were composed of poly(2-hydroxyethyl methacrylate-co-methyl
      methacrylate) (PHEMA-MMA). Two PHEMA-MMA channels, having a mean elastic modulus
      of either 177 or 311 kPa were implanted into T8-transected spinal cords of adult
      Sprague Dawley rats. The cord stumps were inserted into the channels and fibrin
      glue was applied to the cord-channel interface. An expanded
      polytetrafluoroethylene (ePTFE) membrane was used for duraplasty. Controls
      underwent cord transection alone. Gross and microscopic examination of the spinal
      cords showed continuity of tissue within the synthetic guidance channels between
      the cord stumps at 4 and 8 weeks. There was a trend towards an increased area and
      width of bridging neural tissue in the 311-kPa guidance channels compared to the
      177-kPa channels. Neurofilament stained axons were visualized within the bridging
      tissue, and serotonergic axons were found to enter the 311-kPa channel.
      Retrograde axonal tracing revealed regeneration of axons from reticular,
      vestibular, and raphe brainstem motor nuclei. For both channels, there was
      minimal scarring at the channel-cord interface, and less scarring at the channel
      dura interface compared to that observed next to the ePTFE. The present study is
      the first to show that axons from brainstem motor nuclei regenerated in unfilled
      synthetic hydrogel guidance channels after complete spinal cord transection.

PMID- 15253806
TI  - The time course of hydroxyl radical formation following spinal cord injury: the
      possible role of the iron-catalyzed Haber-Weiss reaction.
AB  - This study explores whether the hydroxyl radical (*OH)-one of the most
      destructive reactive oxygen species-plays a role in secondary spinal cord injury
      (SCI). First, we measured the time course of *OH formation in rat spinal tissue
      after impact SCI by administering salicylate as a trapping agent into the
      intrathecal space of the cord and measuring the hydroxylation products of
      salicylate, 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA) by HPLC. The
      2,3-DHBA concentration was significantly higher in injured spinal tissue than in
      sham controls at 5 min, 1 and 3 h, but not at 5 h post-injury. Second, we
      generated *OH by administering H(2)O(2) and FeCl(2)/EDTA (Fenton's reagents) at
      the concentrations produced by SCI into the gray matter of the cord for 4 h and
      found that it induced significant cell loss at 24 h post-*OH exposure. Mn (III)
      tetrakis (4-benzoic acid) porphyrin(MnTBAP)-a broad spectrum reactive species
      scavenger-significantly reduced *OH-induced cell death. Finally, we generated
      superoxide and administered FeCl(3)/EDTA in the intrathecal space of the cord at
      the concentration produced by SCI and measured extracellular *OH formation in the
      gray matter of the cord by microdialysis sampling. We found that the levels of
      *OH significantly increased compared to the pre-administration level, indicating
      that *OH can be produced in vivo by the iron-catalyzed Haber-Weiss reaction. All
      together, we demonstrated that *OH is an endogenous secondary damaging agent
      following SCI and the metal-catalyzed Haber-Weiss reaction may contribute to
      early *OH formation after SCI.

PMID- 15253807
TI  - Autonomic dysreflexia, induced by noxious or innocuous stimulation, does not
      depend on changes in dorsal horn substance p.
AB  - After experimental spinal cord injury (SCI) in rats, autonomic dysreflexia is
      commonly induced by slightly noxious cutaneous or visceral stimuli. The presence
      of autonomic dysreflexia is associated with an increase in the afferent fiber
      arbor area labeled by cholera toxin B or with an anti-CGRP antibody. Our goal was
      to examine further the sensory afferent input contributing to exaggerated
      autonomic spinal reflexes and subsequent increases in blood pressure after SCI,
      typical of autonomic dysreflexia. We observed that changes in blood pressure and
      heart rate induced by slightly noxious stimuli (2.0-mL balloon colon distension,
      cutaneous pinch) were increased in magnitude with time after SCI. In contrast,
      cardiovascular responses induced by non-noxious stimuli (1.0-mL balloon colon
      distension, light stroking of hair) were relatively constant. We examined
      substance P-immunoreactive afferent fibers to identify type C, unmyelinated
      afferent fibers, and A delta lightly myelinated fibers in superficial and deeper
      laminae of the dorsal horn, respectively. The area of substance P-immunoreactive
      fibers was quantified in laminae I-V of the dorsal horn. Analysis revealed no
      difference in substance P afferent fiber area in laminae I-II, or laminae III-V,
      between sham-injured and SCI rats. These data suggest that noxious, or innocuous,
      stimulation induces autonomic dysreflexia without expansion of the central arbors
      of substance P-immunoreactive sensory neurons. Furthermore, autonomic dysreflexia
      induced by noxious stimulation increases with time after spinal cord injury.

PMID- 15253808
TI  - Management of ureteral calculi.

PMID- 15253810
TI  - The birth of fiberoptics from "light guiding".

PMID- 15253809
TI  - Gut-inhabiting bacterium Oxalobacter formigenes: role in calcium oxalate
      urolithiasis.
AB  - Oxalate plays a crucial role in the formation of most renal stones. Oxalate is a
      common constituent of most diets and a byproduct of metabolism, and if it is not
      sufficiently degraded, it may accumulate. In humans, gut bacteria degrade 70 to
      100 mg of oxalate per day. Oxalobacter formigenes is a gram-negative, obligately
      anaerobic, rod-shaped bacterium with an absolute requirement for oxalate.
      Although not present in the gut at birth, it quickly colonizes most children, and
      there is epidemiologic evidence that its absence is a risk factor in calcium
      oxalate stone formation. We review the metabolism, genetics, and identification
      of this organism and its possible therapeutic role in recurrent stone-forming
      patients.

PMID- 15253811
TI  - Ureteropelvic junction obstruction: does CT angiography allow better selection of
      therapeutic modalities and better patient outcome?
AB  - PURPOSE: To determine whether preoperative helical CT angiography (CTA) with
      three-dimensional (3D) reconstructed images improves outcome in patients with
      ureteropelvic junction obstruction (UPJO) by identifying crossing vessels that
      may lead to surgical failure. PATIENTS AND METHODS: Twenty-five patients with
      UPJO underwent imaging with CTA to identify crossing vessels. Patients with
      crossing vessels or severe hydronephrosis underwent laparoscopic dismembered
      pyeloplasty. In the absence of crossing vessels, and with >25% renal function on
      MAG-3 scan, the patient underwent an endopyelotomy. Procedures were assessed as
      successful by resolution of patient symptoms as well as relief of obstruction on
      renal scintography. RESULTS: Twenty-seven procedures (14 laparoscopic dismembered
      pyeloplasties [9 in the setting of a crossing vessel], 11 ureteroscopic
      endopyelotomies, and two antegrade endopyelotomy procedures) were performed.
      Follow-up ranged from 2.4 to 40 months (mean 21.6 months). Twenty-three of the
      primary procedures (92.0%) were successful. Primary laparoscopic pyeloplasty was
      successful in 100% of patients, while primary endopyelotomy had a success rate of
      83.3%. Both secondary procedures were successful rendering the patients
      unobstructed and pain free. No complications occurred. The sensitivity and
      specificity of CTA in determining crossing vessels was 78% and 40%, respectively.
      CONCLUSIONS: Helical CT angiography with 3D reconstructed images provides
      valuable preoperative information in patients with UPJO scheduled for surgical
      intervention. This study may be used in selecting patients for proper operative
      intervention according to the anatomy of crossing vessels to attain high
      treatment success rates.

PMID- 15253812
TI  - Does failure to visualize the ureter distal to an impacted calculus constitute an
      impediment to successful lithotripsy?
AB  - BACKGROUND: A severe degree of ureteral obstruction is viewed as a predictor of
      poor outcome in shockwave lithotripsy (SWL). Impacted stones are often considered
      a contraindication to in-situ SWL. PATIENTS AND METHODS: Impaction in our study
      was defined as failure to visualize the ureter distal to the calculus with
      proximal hold-up of contrast for as long as 3 hours on an intravenous urogram
      (IVU). We evaluated 30 patients with impacted ureteral calculi, who were compared
      with a second unimpacted group matched for stone size and stone location. The
      calculi were reorganized into < or =10-mm and >10-mm groups. The results were
      compared in terms of clearance rates, number of shockwaves, number of sessions,
      and number of days between the start of SWL and clearance. RESULTS: Between
      January 1998 and December 2001, 30 impacted stones were treated with lithotripsy.
      Complete clearance rates in the impacted as well as the non-impacted group were
      76.7%. There was no statistical difference in the number of shockwaves, sessions,
      or time to clearance. The results were poorer in lower-ureteral than upper
      ureteral calculi, but this difference did not reach statistical significance.
      However, the differences between the < or =10-mm and >10-mm stones were
      statistically significant. CONCLUSION: Impaction on an IVU does not affect the
      results of lithotripsy.

PMID- 15253813
TI  - Laparoscopic cryoablation under sonographic guidance for the treatment of small
      renal tumors.
AB  - PURPOSE: To evaluate the efficacy of ultrasound-guided laparoscopic cryoablation
      of small renal tumors. PATIENTS AND METHODS: Eleven men and five women with solid
      renal tumors (mean size 2.6 cm) were treated using laparoscopically monitored
      cryoablation between October 2000 and October 2002. Nine tumors were left sided
      and seven right. Ten patients were treated retroperitoneoscopically and six
      transperitoneally. A double-freeze/active-thaw technique was utilized with two 10
      minute freeze cycles. RESULTS: The mean operating time was 188 minutes. There was
      one open conversion for failure to progress. The mean blood loss was 40 mL. Tumor
      biopsy demonstrated five renal-cell carcinomas, two oncocytomas, and lesions that
      either were benign or were not biopsied. The mean hospital stay was 1.9 days with
      a median stay of 1 day. With a mean follow-up of 9.6 months, all tumors remain
      nonenhancing and are stable or smaller than the original lesion. Two patients
      have died of unrelated causes and without evidence of disease. CONCLUSIONS: This
      series of patients adds to the growing body of literature suggesting that
      cryoablation is a well-tolerated method for treating small renal tumors. Longer
      follow-up is required to fully define its place in the therapeutic armamentarium.

PMID- 15253814
TI  - Laparoscopic extravesical reimplantation for postpubertal vesicoureteral reflux.
AB  - BACKGROUND AND PURPOSE: Postpubertal vesicoureteral reflux is a rare occurrence.
      In the adolescent group, its repair can be a challenging open procedure. We
      present our preliminary experience with laparoscopic extravesical ureteral
      reimplantation for postpubertal vesicoureteral reflux. PATIENTS AND METHODS: Six
      female patients with a mean age of 18.7 years presented with recurrent urinary
      tract infection secondary to vesicoureteral reflux. The indications for treatment
      were febrile urinary tract infection, recurrent pyelonephritis, renal scarring,
      and breakthrough urinary tract infection. The reflux was unilateral in all
      patients at the time of treatment, but one patient had previously experienced
      bilateral reflux and had persistent left-sided reflux following subureteral
      injection of Durasphere. This patient underwent bilateral laparoscopic
      extravesical ureteral reimplantation. RESULTS: The mean operative times for the
      unilateral and bilateral procedures were 1.75 hours and 3.75 hours, respectively.
      The average length of stay in the hospital was 36 hours; five patients went home
      in <24 hours. The mean time to resumption of full activity was 8 days. All six
      patients had resolution of vesicoureteral reflux, as shown by radiographic
      studies, with a mean follow-up of 11.4 months. CONCLUSION: Laparoscopic
      extravesical ureteral reimplantation for postpubertal vesicoureteral reflux has
      excellent outcomes with minimal postoperative morbidity. Long-term radiographic
      follow-up is needed.

PMID- 15253815
TI  - Laparoscopic nephroureterectomy for adult incontinence caused by functioning
      ectopic pelvic kidney draining into vagina.
AB  - A 29-year-old woman had been continent of the majority of her urine for her
      entire life but had constant, uncontrollable dribbling. A contrast CT scan showed
      a solitary functioning left kidney and a dysplastic right pelvic kidney with a
      tortuous dilated ureter running close to the vaginal vault. The kidney was
      removed whole at transperitoneal laparoscopy, rendering the patient continent.
      This is the first such case reported in an adult.

PMID- 15253816
TI  - Bilateral purely laparoscopic nephrectomy for renal masses using five ports
      without repositioning: a case report.
AB  - BACKGROUND AND PURPOSE: Bilateral nephrectomy is an infrequently performed
      procedure. The indications include bilateral masses too large for nephron-sparing
      surgery, recalcitrant hypertension in dialysis patients, pain, infection, reflux,
      or large symptomatic polycystic kidneys. Bilateral pretransplant purely
      laparoscopic nephrectomy for bilateral renal masses has not been reported
      previously. We present our experience with this procedure using five
      transabdominal trocars without having to reposition the patient. METHODS: We
      employed a five-port technique in a middle-aged woman with end-stage renal
      disease who presented with an infected peritoneal dialysis catheter. On abdominal
      CT, she had bilateral enhancing renal masses. Six weeks after removal of the
      catheter, she underwent bilateral transperitoneal laparoscopic nephrectomy. The
      technique is described, and recommendations are made regarding potential
      obstacles. RESULTS: The procedure was performed in 185 minutes, and the total
      hospital time was 41 hours. The estimated blood loss was 50 mL. Final pathology
      examination revealed a 5.5-cm right renal-cell carcinoma stage T1N0M0 and left
      hydronephrosis, atrophy, nephrosclerosis, and thick-walled renal cysts without
      malignancy. On 3-month follow-up she is well, without complaints. CONCLUSION:
      Bilateral pretransplant purely laparoscopic nephrectomy can be performed without
      significant repositioning, redraping, and resterilization. In this case,
      operative time and cosmesis were acceptable, and surgical morbidity was low.

PMID- 15253817
TI  - Use of biopsy sheath to improve standardization of renal mass biopsy in tissue
      ablative procedures.
AB  - PURPOSE: We used a biopsy sheath to standardize and improve biopsy specimens
      obtained during laparoscopic cryoablation. MATERIALS AND METHOD: Tru-Cut biopsy
      was performed using a resized sheath in three patients undergoing laparoscopic
      cryoablation of renal masses. RESULTS: All three biopsy specimens were sufficient
      for pathologic evaluation and representative of the tissue mass. CONCLUSIONS: The
      application of a biopsy sheath to standardize the depth of needle penetration
      during Tru-Cut biopsy provides better results and minimizes false-negative
      studies.

PMID- 15253818
TI  - TissueLink device for laparoscopic nephron-sparing surgery.
AB  - BACKGROUND AND PURPOSE: One of the most challenging aspects of laparoscopic
      partial nephrectomy is achieving adequate control of bleeding from the tumor bed.
      We report our initial experience with laparoscopic nephron-sparing surgery using
      the TissueLink floating-ball radiofrequency dissector. PATIENTS AND METHODS: From
      March 2002 to April 2003, we performed 14 purely laparoscopic nephron-sparing
      nephrectomies using the floating-ball device on 11 patients. RESULTS: The mean
      operative time was 124 minutes (range 90-210 minutes). The mean estimated blood
      loss was 168 mL (range 20-600 mL). One patient had a small urine leak and was
      sent home with the drain in place. CONCLUSIONS: We successfully treated 14 small
      renal lesions using the TissueLink floating-ball device. The procedure was
      performed in an expeditious fashion with minimal blood loss. Long-term follow-up
      is required to determine the oncologic efficacy.

PMID- 15253819
TI  - Pneumothorax masked by subcutaneous emphysema after laparoscopic nephrectomy.
AB  - An 81-year-old man with an enhancing upper-pole renal mass underwent laparoscopic
      nephrectomy via a retroperitoneal approach. Postoperatively, his systolic blood
      pressure declined to 72 mm Hg, and arterial blood gas analysis suggested acute
      respiratory acidosis. Chest radiography suggested subcutaneous emphysema, but a
      CT scan showed tension pneumothorax. This case illustrates the difficulties in
      interpretation of chest films caused by the subcutaneous air that is routinely
      present after laparoscopic procedures.

PMID- 15253820
TI  - Vascular control of the renal pedicle using the hem-o-lok polymer ligating clip
      in 50 consecutive hand-assisted laparoscopic nephrectomies.
AB  - BACKGROUND AND PURPOSE: A crucial step in laparoscopic nephrectomy is control and
      ligation of the renal pedicle. Commonly, an endovascular gastrointestinal
      anastomosis (GIA) stapling device, titanium staples, or both is employed for
      vascular control. Herein, we report on the use of the Hem-o-Lok polymer ligating
      clip (Weck Closure Systems, Research Triangle Park, NC) for the routine control
      of the renal pedicle (both venous and arterial) during hand-assisted laparoscopic
      radical nephrectomies. PATIENTS AND METHODS: From March 2001 to December 2002, 50
      hand-assisted simple or radical nephrectomies were performed by a single surgeon.
      The Hem-o-lok polymer ligating clip was utilized exclusively for ligation of the
      renal pedicle, with placement of two clips on the patient's side and one distally
      on the specimen side. RESULTS: Vascular control was achieved safely in all cases.
      Neither slippage nor complications were found in any of these cases. CONCLUSIONS:
      Vascular control of the renal pedicle via the Hem-o-Lok polymer ligating clip is
      safe and dependable for laparoscopic radical/simple nephrectomies.

PMID- 15253821
TI  - Physical properties of flexible ureteroscopes: implications for clinical
      practice.
AB  - BACKGROUND AND PURPOSE: Physical characteristics may be important in the
      performance of a flexible ureteroscope. This study evaluated the strength of the
      shaft and deflection mechanism of several instruments. MATERIALS AND METHODS:
      Sequential loads were placed along the axis of downward deflection to measure the
      stiffness of the shaft and strength of deflection. Bending pressure was defined
      as the force required to deflect the tip of the ureteroscope 15 degrees from
      baseline. Buckling pressure was defined as the force that resulted in
      catastrophic bending (>90 degrees) of the shaft of the ureteroscope. Strength of
      deflection was defined as the force that resulted in loss of 10 degrees of active
      deflection. RESULTS: Bending pressures were lower for the Olympus URF-P3 (6.4 g)
      and Wolf 7325.172 (6.0 g) ureteroscopes. Similarly, buckling pressures were lower
      for these two ureteroscopes (9.0 g and 11.6 g, respectively). The Wolf and Storz
      flexible ureteroscopes had stronger deflection mechanisms than the Olympus URF-P3
      and the ACMI DUR-8. CONCLUSIONS: This study demonstrates significant differences
      in ureteroscope strength. Higher buckling pressures may facilitate advancement of
      a ureteroscope over a guidewire but may impede secondary deflection. Lower
      bending pressures may facilitate passive intrarenal manipulation. Strength of
      deflection may impact the ability to maintain deflection with an instrument in
      the working channel.

PMID- 15253822
TI  - Retrograde acucise endopyelotomy: is it worth its cost?
AB  - PURPOSE: To identify patients with ureteropelvic junction (UPJ) obstruction who
      will benefit from endoscopic Acucise incision of the stenosis and to compare the
      open Hynes-Anderson pyeloplasty with this minimally invasive technique. PATIENTS
      AND METHODS: In a prospective trial, 22 patients with primary and secondary UPJ
      obstruction were treated by Acucise endopyelotomy, and 18 patients were treated
      by Hynes-Anderson pyeloplasty. Preoperative and postoperative renal scans were
      used to determine the degree of obstruction and intravenous urography, ultrasound
      scanning, or both to assess the degree of dilation. RESULTS: There was a vast
      difference in the cure rate of the two groups: Hynes-Anderson pyeloplasty cured
      94.5% of the patients, while in the Acucise group, the cure rate was only 32%.
      There was some improvement in another 22% of the patients, but the renal scan
      curve remained obstructed. The remaining 45% of patients failed to show any
      improvement. CONCLUSION: Acucise endopyelotomy will improve or cure only patients
      with good renal function and mild dilation of the pelvicaliceal system. Patients
      with severe dilation should be treated by Hynes-Anderson pyeloplasty.

PMID- 15253823
TI  - Supine position is safe and effective for percutaneous nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: The prone position has been widely adopted in
      conventional percutaneous nephrolithotomy (PCNL). Following its introduction in
      1998, we changed our routine practice of PCNL from the prone to the supine
      position, which had numerous benefits and was safe and effective. Tract formation
      and stone fragmentation and retrieval were accomplished with the patient supine.
      PATIENTS AND METHODS: We report our experience with 62 patients (67 renoureteral
      units) treated in the supine position and describe the technique in detail.
      RESULTS: The primary stone clearance rate was 76%, and the mean number of
      sessions of PCNL was 1.3. There was no procedure-related major complication.
      There were also no splanchnic injuries. One kidney loss (emergency nephrectomy
      for control of hemorrhage) was noted but was not directly related to the
      procedure (profuse bleeding after accidental traction on the balloon nephrostomy
      tube by the patient 1 week after PCNL). Modification of positioning was made to
      suit the body build of Chinese patients. CONCLUSION: There are several advantages
      to the supine position for the patient and the urologist, with greater
      versatility of stone manipulation along the whole upper urinary tract. There are
      a few limitations of the supine position, but they can be overcome. Performing
      PCNL with the patient in the supine position is a sound alternative to the
      conventional prone position.

PMID- 15253824
TI  - Totally tubeless percutaneous nephrolithotomy in selected patients.
AB  - PURPOSE: Significant early postoperative discomfort after percutaneous procedures
      is usually secondary to nephrostomy tubes and externalized ureteral catheters. We
      describe our modification of the traditional percutaneous nephrolithotomy (PCNL)
      approach that we name "totally tubeless PCNL." PATIENTS AND METHODS: Between June
      2000 and May 2001, 60 consecutive PCNLs were performed at our centers. At the end
      of the surgery, we omitted the nephrostomy tube and removed the externalized
      catheter in selected patients: no solitary kidney, stone size <3 cm, and without
      any obstructions or arterial bleeding. A total of 30 patients underwent totally
      tubeless PCNL (group 1). We compared their results with those of a control group
      of 30 patients who underwent standard PCNL (group 2). The incidence of
      complications, analgesic requirements, length of hospitalization, and time to
      return to normal activities were compared in the two groups. RESULTS: In both
      groups, PCNL was performed successfully without any significant complications. A
      90% stone-free rate was achieved in both groups, and in the remaining patients,
      small residual stones (<4 mm) were detected. No urinoma was demonstrated by
      postoperative ultrasound scanning in group 1. The average length of
      hospitalization was 1.5 days for group 1 and 3 days for group 2. The average
      analgesic requirements were 30 mg of pentazosin in group 1 and 90 mg in group 2.
      No transfusion was needed. There were three complications: 2 patients (6.6%) had
      urinary tract infection in group 1 and 1 (3.3%) in group 2. All were managed
      medically. CONCLUSIONS: Omitting the percutaneous nephrostomy tube and removing
      ureteral catheter at the end of surgery in selected patients were safe and
      accompanied by significantly reduced postoperative discomfort, length of
      hospitalization, and analgesic requirements. Further studies are needed to
      determine the role of this technique.

PMID- 15253825
TI  - Controversial cases in endourology & opinions. An otherwise-healthy 72-year-old
      man presents 6 years after open right radical nephrectomy for stage T2 Fuhrman
      grade II renal-cell carcinoma with two findings in his solitary kidney.

PMID- 15253826
TI  - Reflux of a staple after kock pouch urinary diversion: a nidus for renal stone
      formation.
AB  - A patient with cystectomy and urinary diversion after spinal cord injury had
      multiple pouch concretements and a kidney stone formed around a staple that
      apparently had refluxed from the nipple of the pouch. In such cases, the stone
      and staple should be removed at the same time, either percutaneously or by
      ureterorenoscopy.

PMID- 15253827
TI  - Instillation of anesthetic gel is no longer necessary in the era of flexible
      cystoscopy: a crossover study.
AB  - BACKGROUND AND PURPOSE: Whether urethral injection of anesthetic and lubricating
      gel prior to outpatient flexible cystoscopy is worthwhile with regard to pain
      tolerance has been investigated only in a parallel randomized study. A crossover
      study was thus designed for further elucidation. PATIENTS AND METHODS: Each of 33
      male patients underwent three flexible cystoscopic examinations with
      intraurethral instillation of 11 mL of cold anesthetic gel (group 1), plain
      lubricating gel (group 2), or no gel (group 3). In every examination, 2%
      lidocaine gel was applied to the cystoscope. Although the cystoscopy was
      performed by two urologic surgeons, each patient underwent the three consecutive
      examinations with the same urologist. All the patients separately recorded pain
      levels during gel instillation, cystoscope insertion, and intravesical
      observation on a 100-mm visual analog scale after every cystoscopy. RESULTS: From
      the median scores, the degree of pain resulting from gel injection was 77.0% and
      98.0% of those for cystoscope insertion and intravesical observation,
      respectively. For each group stratified by anesthetic method, there was no
      significant difference in the pain score during either cystoscope insertion or
      intravesical observation. CONCLUSION: The pain caused by intraurethral gel
      instillation is significant compared with that from cystoscope insertion and
      intravesical observation. Anesthetic gel instillation appears to have no
      significant advantage over anesthesia-free flexible cystoscopic examinations.

PMID- 15253828
TI  - Vesicovaginal fistula repair: transurethral suture cystorrhaphy as a minimally
      invasive alternative.
AB  - Further experience and success in the transurethral repair of vesicovaginal
      fistula (VVF) prompted a review of our current technique and results. Patient
      selection criteria, instrumentation, technique, and potential pitfalls are
      discussed.

PMID- 15253830
TI  - Trichobezoar of urinary bladder with secondary calculus: case report.
AB  - A trichobezoar with a calculus in the center was diagnosed in a young woman on
      long-term urethral catheter drainage. Urologists need to be aware of this
      potentially preventable complication to save patients from significant morbidity.

PMID- 15253829
TI  - Pneumatic lithotripter application for giant bladder stone in a patient with
      augmentation cystoplasty.
AB  - An 18-year-old patient with repaired bladder exstrophy developed a 550-g stone
      burden in his augmented bladder. The stones were removed percutaneously with the
      aid of a pneumatic lithotripter. This should be considered the method of choice
      in these difficult cases.

PMID- 15253831
TI  - Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate
      cancer.
AB  - PURPOSE: To examine the feasibility and potential of magnetic fluid hyperthermia
      (MFH) as a minimally invasive method for hyperthermia treatment of prostate
      cancer. MATERIALS AND METHODS: Orthotopic Dunning R3327 prostate tumors were
      induced in 20 male Copenhagen rats. The animals either received MFH treatment
      following intratumoral administration of magnetic fluids or were used as either
      tumor growth controls for determination of iron distribution in selected organs
      or as histologic controls without MFH treatment. The MFH treatments were carried
      out at 45 degrees C or 50 degrees C using an AC magnetic field applicator system
      designed for small animals. RESULTS: Sequential treatments with MFH were possible
      following a single intratumoral injection of magnetic fluid. Intratumoral
      temperatures of 50 degrees C and more were obtained and were monitored online
      using fluoro-optic thermometry. Four days after MFH treatments, 79% of the
      injected dose of ferrites was still present in the prostate. CONCLUSIONS: The
      successful intraprostatic nanoparticle infiltration and stable steady-state
      intratumoral treatment temperatures demonstrate the feasibility of MFH in a
      prostate cancer model. Efficacy and survival benefit must be confirmed in further
      experiments.

PMID- 15253832
TI  - Comparison of radiofrequency ablation, cryoablation, and nephrectomy in treating
      implanted VX-2 carcinoma in rabbit kidneys.
AB  - PURPOSE: To compare the efficacy of radiofrequency (RF) ablation, cryoablation,
      and radical nephrectomy in the treatment of implanted VX-2 carcinoma in rabbit
      kidneys. MATERIALS AND METHODS: Sixty-eight New Zealand White rabbits were
      implanted with 1-mm3 segments of VX-2 carcinoma in the left kidney. Seven days
      after implantation, the tumors were treated with one of the following: (1) RF
      ablation using a 12-gauge electrode (RITA Medical Systems, Mountain View, CA) at
      90 degrees C for 8 minutes with a 5-mm tumor margin target temperature of 60
      degrees C (N = 20); (2) cryoablation using a 15 minute double-freeze technique
      with 2.4-mm cryoprobes and the Cryocare system (Endocare Inc., Irvine, CA) with a
      5-mm tumor margin target temperature of -20 degrees C (N = 20); (3) open radical
      nephrectomy (N = 20); or (4) no treatment (controls; N = 8). Rabbits were allowed
      to survive for a total of 22 days and sacrificed; and the kidneys, lungs, liver,
      spleen, urinary bladder, and ureter were removed and examined grossly and
      histologically for tumor. RESULTS: Findings in animals sacrificed at 15 days post
      treatment showed significant differences between all treatment groups and
      untreated controls (P < 0.002) Using a 3 x 2 chi-square comparison, no
      differences in disease-free survival were observed between the RF ablation group,
      the cryoablation group, and the open nephrectomy group (P = 0.72) CONCLUSION:
      Radiofrequency ablation, cryoablation, and radical nephrectomy were all
      efficacious in the treatment of implanted VX-2 renal tumors compared with
      untreated controls (P = 0.002). No statistically significant difference was found
      between any of the three treatments.

PMID- 15253833
TI  - Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in
      a porcine model.
AB  - PURPOSE: Small-intestinal submucosa (SIS) has been successful as an onlay graft
      in ureteral repair, but tubularized segment interposition of SIS has been
      unsuccessful. Our objective was to evaluate whether a type I collagen inhibitor,
      halofuginone, would prevent stricture formation in tubularized SIS interposition.
      MATERIALS AND METHODS: We performed either laparoscopic partial ureteral excision
      followed by an SIS onlay graft (N = 5) or complete laparoscopic ureteral excision
      followed by an SIS interposition graft (N = 7) in domestic pigs. Animals received
      either no (N = 3), low-dose (N = 5), or high-dose (N = 4) halofuginone. Animals
      had ureteral stenting for 2 weeks after surgery and were permitted to survive for
      6 or 9 weeks. An intravenous urogram (IVU) was performed prior to sacrifice.
      Kidneys were examined grossly and histologically. RESULTS: One animal that
      received an onlay graft died of an unrelated illness. The remaining four ureteral
      onlay animals, including one control and two low-dose and one high-dose pig, had
      grossly normal kidneys at harvest. The IVU was normal in the control and high
      dose animal but showed delayed excretion with mild hydroureteronephrosis in the
      low-dose animals. Pathologic examination of the SIS site revealed circumferential
      reepithelialization with inflammation and mild fibrosis. All seven tubularized
      interposition graft kidneys demonstrated either severe hydroureteronephrosis (N =
      5) or renal atrophy (N = 2), and all had complete obstruction on IVU. Pathologic
      examination revealed a stenotic ureteral lumen with extensive surrounding
      inflammation and fibrosis. CONCLUSIONS: An SIS onlay graft was successful in the
      porcine model of ureteral injury. Halofuginone, a type I collagen inhibitor, did
      not demonstrate a significant beneficial effect in this technique. Ureteral
      tubularized interpositions with SIS are unsuccessful and not improved by
      halofuginone.

PMID- 15253834
TI  - Re: Transurethral resection of prostate and suprapubic ballistic
      vesicolithotripsy for benign prostatic hyperplasia with vesical calculi (Kamat et
      al; J Endourol 2003; 17:505-510) and Per-urethral endoscopic management of
      bladder stones: does size matter? (Sathaye et al; J Endourol 2003; 17: 511-514).

PMID- 15253835
TI  - Archean microfossils and abiomorphs.

PMID- 15253836
TI  - Many chemistries could be used to build living systems.
AB  - It has been widely suggested that life based around carbon, hydrogen, oxygen, and
      nitrogen is the only plausible biochemistry, and specifically that terrestrial
      biochemistry of nucleic acids, proteins, and sugars is likely to be "universal."
      This is not an inevitable conclusion from our knowledge of chemistry. I argue
      that it is the nature of the liquid in which life evolves that defines the most
      appropriate chemistry. Fluids other than water could be abundant on a cosmic
      scale and could therefore be an environment in which non-terrestrial biochemistry
      could evolve. The chemical nature of these liquids could lead to quite different
      biochemistries, a hypothesis discussed in the context of the proposed
      "ammonochemistry" of the internal oceans of the Galilean satellites and a more
      speculative "silicon biochemistry" in liquid nitrogen. These different
      chemistries satisfy the thermodynamic drive for life through different
      mechanisms, and so will have different chemical signatures than terrestrial
      biochemistry.

PMID- 15253837
TI  - The biological terraforming of Mars: planetary ecosynthesis as ecological
      succession on a global scale.
AB  - Mars is bitterly cold and dry, but robotic spacecraft have returned abundant data
      that indicate Mars once had a much warmer and wetter climate in the past. These
      data, the basis of the search for past or present life on Mars, suggest the
      possibility of returning Mars to its previous climate by global engineering
      techniques. Greenhouse gases, such as perfluorocarbons, appear to be the best
      method for warming Mars and increasing its atmospheric density so that liquid
      water becomes stable. The process of making Mars habitable for terrestrial
      organisms is called terraforming or planetary ecosynthesis. The process of
      introducing terrestrial ecosystems to Mars can be compared with a descent down a
      high mountain. Each drop in elevation results in a warmer, wetter climate and
      more diverse biological community. Beginning with a polar desert, the sequence of
      ecosystems passes through tundra, boreal forest, and temperate ecosystems where
      moisture determines the presence of desert, grassland, or forest. This model
      suggests a sequence for the introduction of ecosystems to Mars and the
      communities to search for potential colonizing species for Mars.

PMID- 15253838
TI  - A transmission electron microscopy study of silica and kerogen biosignatures in
      approximately 1.9 Ga gunflint microfossils.
AB  - Microfossils preserved in chert from the;1.9 Ga Gunflint Formation (Schreiber
      Beach, Ontario, Canada) were studied with transmission electron microscopy (TEM)
      and analytical TEM (ATEM). Our goals were to uncover the style of silicification
      relative to the distribution of organic matter, and to evaluate the distribution
      and evolution of organic matter, at submicroscopic spatial scales.
      Petrographically the microfossils typically display filamentous or coccoidal
      morphologies, and consist of quartz crystals surrounded by kerogen along grain
      boundaries. ATEM analysis revealed that quartz associated with kerogen consists
      of 200-500nm-sized, round crystallites, whereas the chert matrix is comprised of
      randomly oriented, polygonal microquartz (5-10 microm). Silica spheroids found
      within some fossils consist of quartz subgrains in an amorphous to poorly
      crystalline matrix, suggesting that precipitation of opaline silica on organic
      matter occurred with subsequent but incomplete transformation to quartz. Some
      coccoidal microfossils surround large euhedral quartz crystals (up to 5 microm in
      diameter) that appeared to have influenced the distribution of kerogen during
      crystal growth. These euhedral quartz crystals commonly contain elongated (50-100
      nm) iron-rich crystallites. Energy-loss, near-edge structure analysis of kerogen
      associated with a coccoidal microfossil showed that it is composed of amorphous
      carbon with no evidence of graphitization. TEM results revealed significant
      differences in the style of silicification between microbe-shaped microfossils
      and their surrounding chert matrix, as well as the presence of amorphous kerogen.

PMID- 15253839
TI  - Condensation reactions and formation of amides, esters, and nitriles under
      hydrothermal conditions.
AB  - Hydrothermal pyrolysis experiments were performed to assess condensation
      (dehydration) reactions to amide, ester, and nitrile functionalities from lipid
      precursors. Beside product formation, organic compound alteration and stability
      were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or
      hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at
      300 degrees C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic
      acid solutions were used to test the abiotic formation of organic nitrogen
      compounds at the same temperature. The resulting products were condensation
      compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides,
      alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded
      mainly hydrolysis and dehydration products, and with ammonium bicarbonate and
      oxalic acid the yield of condensation products was enhanced. The synthesis
      experiments with oxalic acid and ammonium bicarbonate solutions yielded
      homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all
      with no carbon number predominances. These organic nitrogen compounds are stable
      and survive under the elevated temperatures of hydrothermal fluids.

PMID- 15253840
TI  - The temporal aspect of the drake equation and SETI.
AB  - We critically investigate some evolutionary aspects of the famous Drake equation,
      which is usually presented as the central guide for research on extraterrestrial
      intelligence. It is shown that the Drake equation tacitly relies on unverified
      assumptions on both the physicochemical history of our galaxy and the properties
      of advanced intelligent communities. In this manner, the conventional approach
      fails to take into account various evolutionary processes forming prerequisites
      for quantification of the Drake equation parameters. The importance of recent
      results of Lineweaver and collaborators on chemical build-up of inhabitable
      planets for the search for extraterrestrial intelligence is emphasized. Two
      important evolutionary effects are briefly discussed, and the resolution of the
      difficulties within the context of the phase-transition astrobiological models is
      sketched.

PMID- 15253843
TI  - Is "energy medicine" a good label for acupuncture?

PMID- 15253844
TI  - Restless legs syndrome.

PMID- 15253845
TI  - Maca culture of the Junin Plateau.

PMID- 15253846
TI  - A controlled trial of aromatherapy for agitation in nursing home patients with
      dementia.
AB  - OBJECTIVES: Two controlled trials of aromatherapy to decrease agitation in
      persons with dementia have recently produced promising results. However, both
      studies combined the use of essential oils with massage. Thus, it is unclear if
      the effect of the aromatherapy intervention was the result of smelling or the
      cutaneous absorption of the oils. The purpose of this study was to determine
      whether smelling lavender oil decreases the frequency of agitated behaviors in
      patients with dementia. DESIGN: The study design was within-subjects ABCBA (A =
      lavender oil, B = thyme oil, C = unscented grapeseed oil): 4 weeks of baseline
      measurement, 2 weeks for each of the five treatment conditions (10-week total
      intervention time), and 2 weeks of postintervention measurement. Oil was placed
      every 3 hours on an absorbent fabric sachet pinned near the collarbone of each
      participant's shirt. SETTING: A long-term care facility specifically for persons
      with dementia. PARTICIPANTS: Seven agitated nursing home residents with advanced
      dementia. MEASUREMENTS: Agitation was assessed every 2 days using a modified
      Cohen-Mansfield Agitation Inventory. Olfactory functioning was assessed with
      structured olfactory identification and discrimination tasks, and with
      qualitative behavioral observation during those tasks. RESULTS: Split-middle
      analyses conducted separately for each patient revealed no treatment effects
      specific to lavender, no treatment effects nonspecific to pleasant smelling
      substances, and no treatment effects dependent on order of treatment
      administration. There were no differences between participants with more and less
      intact olfactory abilities. CONCLUSION: There is significant evidence in the
      neurologic and neuropsychologic literature that persons with dementia have
      impaired olfactory abilities. Concordant with this literature, this study found
      no support for the use of a purely olfactory form of aromatherapy to decrease
      agitation in severely demented patients. Cutaneous application of the essential
      oil may be necessary to achieve the effects reported in previous controlled
      studies.

PMID- 15253847
TI  - A randomized trial of the effects of remote intercessory prayer: interactions
      with personal beliefs on problem-specific outcomes and functional status.
AB  - OBJECTIVES: Investigate the relevance of interpersonal belief factors as
      modifiers of the effectiveness of intercessory prayer. DESIGN: Randomized
      clinical trial. SETTING/LOCATION: Community-dwelling adults recruited from seven
      local church groups. SUBJECTS: Eighty-six (86) male and female participants 18-88
      years of age were randomly assigned to either treatment (n = 45) or control
      groups (n = 41). INTERVENTIONS: Several volunteers committed to daily prayer for
      participants in the intervention group. Intercessory prayer commenced for 1 month
      and were directed toward a life concern or problem disclosed by the participant
      at baseline. Participants were unaware of being prayed for. OUTCOMES MEASURES:
      Degree to which their problem had been resolved and the current level of concern
      they had about a specific life problem they described at baseline. Four component
      scores from the Medical Outcomes Study SF-20 were also used. RESULTS: No direct
      intervention effect on the primary outcomes was found. A marginally significant
      reduction in the amount of pain was observed in the intervention group compared
      to controls. The amount of concern for baseline problems at follow-up was
      significantly lower in the intervention group when stratified by subject's
      baseline degree of belief that their problem could be resolved. Prayer
      intervention appeared to effectively reduce the subject's level of concern only
      if the subject initially believed that the problem could be resolved. Those in
      the intervention group who did not believe in a possible resolution to their
      problem did not differ from controls. Better physical functioning was observed in
      the intervention group among those with a higher belief in prayer and
      surprisingly, better mental health scores were observed in the control group with
      lower belief in prayer scores. CONCLUSIONS: The results of the current study
      underscore the role of interpersonal belief in prayer efficacy and are consistent
      with the literature showing the relevance of belief in health and well-being in
      general. The relevance of interpersonal belief factors of the participants is
      recommended in future investigations.

PMID- 15253848
TI  - Effect of acupuncture administered in a group setting on pain and subjective
      peripheral neuropathy in persons with human immunodeficiency virus disease.
AB  - OBJECTIVES: The present study was performed to determine the effect of 5 weeks of
      acupuncture treatment in a group setting on pain and symptoms of peripheral
      neuropathy in human immunodeficiency virus (HIV)infected individuals. DESIGN:
      Twenty-one (21) subjects completed the study that consisted of a pretreatment and
      post-treatment case series design. The subjects completed the Pain Rating Scale
      and the Subjective Peripheral Neuropathy Screen (SPNS) before and after 5 weeks
      of acupuncture. The acupuncture treatments occurred two evenings per week. Each
      of the 10 sessions consisted of participants receiving 10-15 needle insertions in
      acupoints that addressed the individual's changing pattern of pain, sleep
      problems, or other health issues. The treatment utilized only main or common
      points located below the elbows and knees, and on the head, neck, and ears. Only
      reactive points were used in the acupuncture treatments. Needles were left in
      situ for 30-45 minutes. RESULTS: Comparison of the pretreatment and post
      treatment Pain Rating Scale results indicated a significant reduction in present
      pain (p = 0.0002), least and most pain in the last 24 hours (p < 0.0001 and p =
      0.0004, respectively) and the total pain summary score (p < 0.0001). Symptoms
      reported in the SPNS were reduced during the 5 weeks of acupuncture. Scores for
      pain/aching/burning, pins and needles, and numbness in the hands and feet were
      reduced (all significant at less than p = 0.0065), as well as the total summary
      score (p = 0.0001). CONCLUSION: The results of this study indicate that
      subjective pain and symptoms of peripheral neuropathy were reduced during the
      period of individual acupuncture therapy delivered in a group setting. While the
      study design did not allow for control of nonspecific placebo factors, the data
      support the hypothesis that acupuncture in a group setting can reduce pain and
      neuropathic symptoms in HIV-infected individuals.

PMID- 15253849
TI  - Effects of qi therapy (external qigong ) on premenstrual syndrome: a randomized
      placebo-controlled study.
AB  - OBJECTIVES: To assess the effects of qi therapy on premenstrual symptoms in women
      with premenstrual syndrome (PMS). DESIGN: A randomized placebo-controlled trial.
      SUBJECTS: Thirty-six (36) college women with symptoms of PMS. INTERVENTION: After
      2 months of screening, subjects with PMS were randomized to receive real qi
      therapy (18 subjects) or placebo (18 subjects). The subjects were informed that
      they would receive one of two types of treatment. They did not know which
      treatment they received. Each intervention was performed eight times during the
      second and third cycles with subjects completing a PMS diary. RESULTS: There were
      significant improvements in the symptoms of negative feeling, pain, water
      retention, and total PMS symptoms in subjects receiving qi therapy compared to
      placebo controls. CONCLUSION: Qi therapy may be an effective complementary
      therapy for managing the symptoms of PMS.

PMID- 15253850
TI  - Biofield perception: a series of pilot studies with cultured human cells.
AB  - BACKGROUND: Energy medicine (EM) practitioners often claim to be able to perceive
      an energetic field associated with the body and to be able to use this skill to
      diagnose illness and guide treatment strategies. If a biofield associated with
      cells growing in culture is perceptible to EM practitioners, such an in vitro
      model would be a useful resource for investigating biofield perception that would
      provide some unique advantages over clinical models. OBJECTIVE: To evaluate
      whether EM practitioners can perceive the presence of cultured human cells
      without visual cues. DESIGN: Three randomized double-blinded pilot studies were
      used to evaluate the ability of participants to distinguish a flask containing
      cancer cells growing in culture medium from a flask containing either culture
      medium or sterile water. Each study consisted of six independent experiments:
      three with EM practitioners and three with non-practitioners. The number of
      independent trials for each experiment was estimated by statistical power
      analyses of the design. Practitioners' feedback from the first two studies was
      used to revise the protocol for the subsequent studies, with the intent to
      eliminate potential problems in making this distinction. Labeled flasks ("cells"
      and "no-cells") were added to serve as references for comparison in the second
      study and the number of experimental trials was reduced in the third study.
      SUBJECTS: Eight experienced EM practitioners and nine non-practitioners
      (laboratory personnel with no EM training). SETTING: A basic science laboratory
      and office at an academic medical center. OUTCOME MEASURES: In the first 2
      studies, we determined the number of correct determinations in a series of 34
      trials. In the third study, we determined the number of correct determinations in
      a series of 10 trials. RESULTS: All participants performed at the level expected
      by chance. CONCLUSION: While preliminary and inconclusive, these pilot studies
      found no evidence that EM practitioners can perceive a biofield associated with
      cancer cells growing in culture.

PMID- 15253851
TI  - Clinical research on acupuncture. Part 1. What have reviews of the efficacy and
      safety of acupuncture told us so far?
AB  - OVERVIEW AND METHODS: This paper discusses those medical conditions in which
      clinical trials of acupuncture have been conducted, and where meta-analyses or
      systematic reviews have been published. It focuses on the general conclusions of
      these reviews by further examining official reviews conducted in the United
      States, United Kingdom, Europe, and Canada each of which examined available
      systematic reviews. While all reviews agree that the methodological rigor of
      acupuncture clinical trials has generally been poor and that higher quality
      clinical trials are necessary, this has not completely hampered the
      interpretation of the results of these clinical trials. In some conditions the
      evidence of efficacy has clearly reached a sufficient critical mass from enough
      well-designed studies to draw clear conclusions; for the rest, the evidence is
      difficult to clearly interpret. This paper also examines conclusions from the
      same international reviews on the safety and adverse effects of acupuncture.
      Here, conclusions are more easily drawn and there is good agreement about the
      safety of acupuncture. RESULTS AND CONCLUSIONS: General international agreement
      has emerged that acupuncture appears to be effective for postoperative dental
      pain, postoperative nausea and vomiting, and chemotherapy-related nausea and
      vomiting. For migraine, low-back pain, and temporomandibular disorders the
      results are considered positive by some and difficult to interpret by others. For
      a number of conditions such as fibromyalgia, osteoarthritis of the knee, and
      tennis elbow the evidence is considered promising, but more and better quality
      research is needed. For conditions such as chronic pain, neck pain, asthma, and
      drug addiction the evidence is considered inconclusive and difficult to
      interpret. For smoking cessation, tinnitus, and weight loss the evidence is
      usually regarded as negative. Reviews have concluded that while not free from
      serious adverse events, they are rare and that acupuncture is a relatively safe
      procedure.

PMID- 15253852
TI  - Clinical research on acupuncture. Part 2. Controlled clinical trials, an overview
      of their methods.
AB  - There is almost universal agreement that the quality of clinical trials of
      acupuncture is poor. There is an urgent need to improve their quality. The author
      develops here a list of 45 criteria important in the design, implementation, and
      writing up of controlled clinical acupuncture trials. This list has been compiled
      after examining the quality assessment criteria used in meta-analyses and
      systematic reviews of acupuncture, general publications on clinical trial designs
      and methodological considerations specific to acupuncture trials. Each criterion
      is discussed with recommendations about use and implementation. Additionally,
      each criterion is discussed relative to their importance in three types of
      acupuncture trial, acupuncture versus sham acupuncture, acupuncture versus
      standard therapy and acupuncture versus no treatment or wait-list. It is hoped
      that this exploration and systematic presentation of the 45 criteria will
      contribute to improving the quality of clinical trials of acupuncture. Improved
      trial quality will lead to greater ease interpreting the results of trials,
      especially in systematic reviews.

PMID- 15253853
TI  - Are the therapeutic effects of homeopathy attributed to the consultation, the
      homeopathic remedy, or both? A protocol for a future exploratory feasibility
      trial in patients with rheumatoid arthritis.
AB  - Systematic reviews suggest that homeopathy has a greater effect than placebo,
      however, the mechanisms of its action are unknown. The clinical effects of
      homeopathy could be attributed to the specific effects of the remedy and/or to
      the contextual effects of the consultation process; these factors have not been
      critically evaluated. We have developed a model that attempt to separate the
      consultation effects from the specific effects because of the remedy. We propose
      to investigate this design in a chronic condition, rheumatoid arthritis, for
      which previous research has evaluated both classical and complex homeopathic
      interventions. The following protocol describes the study design. The aims of
      this exploratory trial are to assess the feasibility of the study design,
      identify effect sizes of the consultation, the complex treatment, and the
      individualized remedy, as well as possibly efficacy, for the two types of
      homeopathic treatment and the homeopathic consultation. Data collection will take
      place in 2004.

PMID- 15253854
TI  - Attitudes about complementary and alternative medicine did not predict outcome in
      a homeopathic proving trial.
AB  - OBJECTIVES: A homeopathic proving states that when a homeopathic remedy is given
      to a healthy person, they will experience symptomatic effects specific to that
      remedy. The aim of this study was to assess if attitudes about complementary and
      alternative medicine (CAM) predicted proving outcome. DESIGN: An exploratory
      study nested in a double blinded randomized controlled proving trial of the
      remedy Belladonna C30. SUBJECTS: Two hundred and six (206) healthy subjects took
      part in the reproving trial of whom 29 (14%) proved. INTERVENTIONS: Subjects
      completed the Attitudes to Alternative Medicine Scale prior to participating in
      the proving trial (n = 206) and after the proving trial was completed (n = 77).
      OUTCOME MEASURES: The primary outcome was whether attitude to CAM predicted
      proving outcome. RESULTS: Attitudes about CAM at baseline did not predict proving
      outcome (chi2 = 35.34, df = 36, p = 0.50) and attitudes to CAM did not alter
      after taking part in the proving trial for either provers or non provers.
      CONCLUSION: Subjects classified as being provers in a proving trial did not have
      significantly different attitudes about CAM than nonprovers. The experience of
      proving the study remedy did not alter the prover's attitudes about CAM.

PMID- 15253855
TI  - Implementation of outcome measures in a complementary and alternative medicine
      clinic: evidence of decreased pain and improved quality of life.
AB  - OBJECTIVES: The purpose of this study was twofold: (1) to design and implement a
      practical data collection system capable of obtaining pain and quality-of-life
      outcome measures in a complementary and alternative medicine (CAM) outpatient
      clinic and (2) to evaluate changes in patient status over time using these
      objective measures. DESIGN: A prospective study was carried out in an outpatient
      practice based setting. Scannable forms were designed utilizing Cardiff's
      TELEform system (Cardiff Software, Inc., Vista, CA) for data collection.
      SETTING/LOCATION: This study was conducted at Special Care Holistic Wellness
      Connection, an urban-based, hospital-affiliated, CAM clinic in Connecticut.
      SUBJECTS: Inclusion criteria consisted of: a starting pain level of 2 or more,
      subjects receiving 3 or more treatments in a specific modality, and a completed
      SF-12v2 Health Survey (Quality Metric Inc., Lincoln, RI). A total of 94 subjects
      were evaluated for acupuncture, chiropractic, or naturopathy. OUTCOME MEASURES:
      The Numeric Pain Analogue Scale and SF-12v2 Health Survey were used for subject
      evaluations and were compared from the first to the last treatments.
      International Classification of Disease codes were utilized to correlate and
      track the diagnosis. RESULTS: An outcome measures data management system was
      successfully implemented into a CAM outpatient clinical setting. Significant
      decreases in pain were observed in subjects receiving acupuncture, chiropractic,
      or naturopathy. In addition, improvements in various subscales of the SF-12v2
      Physical and Mental Health categories were observed for each CAM treatment
      modality studied. CONCLUSIONS: This study established that a practical data
      collection system could be implemented in a CAM clinic utilizing several
      treatment modalities. In addition, outcome measures demonstrated both a
      significant reduction in pain and improvement in quality of life for subjects who
      utilized acupuncture, chiropractic, or naturopathy treatments.

PMID- 15253856
TI  - Korean anti-inflammatory compound allergina enhances cardiac contractile function
      in isolated ventricular cardiomyocytes.
AB  - OBJECTIVES: The herbal compound Allergina has a long history in the clinical
      treatment of allergic inflammatory diseases in some countries including Korea.
      However, the direct effect of Allergina on ventricular contractile function has
      not been defined. DESIGN: This study was designed to investigate the impact of
      Allergina on ventricular contractile function. SETTINGS: Ventricular contractile
      function was examined in single isolated left ventricular cardiomyocytes.
      SUBJECTS/INTERVENTIONS: Isolated cardiomyocytes from adult male Sprague-Dawley
      rats were electrically stimulated to contract at 0.5 Hz. OUTCOME MEASURES:
      Mechanical and intracellular Ca2+ transients properties of cardiomyocytes were
      evaluated using an IonOptix Myocam (IonOptix Inc., Milton, MA) system and fura-2
      fluorescent dye. Contractile properties analyzed included peak shortening (PS),
      time-to-peak shortening (TPS), time-to-90% relengthening (TR90), and maximal
      velocity of shortening/relengthening (+/- dL/dt). Intracellular Ca2+ transients
      were evaluated as the fura-fluorescence intensity change (DeltaFFI) and
      fluorescence decay time. RESULTS: Allergina (10(-7) - 10(-3) mg/mL) significantly
      augmented PS in a dose-dependent manner with a maximal response of 50.4%.
      Allergina did not elicit any effect on TPS, TR(90), and +/-dL/dt. Intracellular
      Ca2+ transients displayed consistent findings in that Allergina enhanced the
      electrically-stimulated increase in change of intracellular Ca2+ transients
      (DeltaFFI) and slowed intracellular Ca2+ fluorescence decay without affect the
      resting intracellular Ca2+ levels. CONCLUSIONS: Collectively, these data
      demonstrated a direct cardiac stimulatory property of Allergina on cardiac
      contraction and intracellular Ca2+ transients in isolated left ventricular
      cardiomyocytes.

PMID- 15253857
TI  - Yin zi huang, an injectable multicomponent chinese herbal medicine, is a potent
      inhibitor of T-cell activation.
AB  - OBJECTIVES: The clinical efficacy of many multiherbal Traditional Chinese
      Medicines (TCM) is partially attributable to their immunoregulatory properties.
      In this study we evaluated the effect of eight commonly used, commercially
      available multiherbal Chinese medicines on T-cell activation. We focused on Yin
      Zhi Huang (YZH, an injectable herbal medicine commonly used for the treatment of
      liver diseases in China), because it was the most potent inhibitor of T-cell
      activation in our experimental system. The effects of 10 ingredient components of
      YZH were also evaluated. METHODS: [3H] thymidine incorporation assay was used to
      assess mouse T-cell proliferation after stimulation with latex beads coated with
      anti-CD3/CD28 antibodies. CD25, CD69, PD-1, and I-COS expression by purified
      mouse CD4+ T cells treated with plate-bound anti-CD3 antibody and soluble anti
      CD28 antibody was analyzed by fluorescent-activated cell sorter (FACS).
      Cytokine/chemokine production by human peripheral blood mononuclear cells (PBMC)
      stimulated with staphylococcal enterotoxin B (SEB) was determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Among tested herbal medicines, YZH
      was the most potent inhibitor of T-cell activation. In splenocyte proliferation
      assays, the inhibitory effect of YZH was dose-dependent, with a 50% inhibition
      concentration (IC50) of 1:3200-1:1600. Ten (10) purified compounds found in YZH
      were evaluated for their activity. Among them, ursolic acid (1-10 micromol),
      luteolin (1-10 micromol), baicalein (1-10 micromol), scopran (5-50 micromol), and
      crocin (5-50 micromol), exhibited dose-dependent inhibition. YZH also inhibited
      CD25, CD69, PD-1, and ICOS expression by stimulated mouse CD4+ T cells. In human
      PBMCs, YZH inhibited SEB-stimulated cytokine (interleukin [IL]-1, IL-2, IL-6,
      tumor necrosis factor[TNF]-alpha, interferon [IFN]-gamma) and chemokine (IP-10,
      MCP-1, MIP-1alpha and MIP-1beta) production in a dose-dependent manner.
      CONCLUSION: Our data show for the first time that YZH is a potent inhibitor of T
      cell activation, and this property may be the major mechanism underlying the
      clinical efficacy of YZH. Our experimental results pave the way for
      identification of active component(s) and/or analysis of synergistic/additive
      effect of a YZH ingredient in future studies.

PMID- 15253858
TI  - Asian pear pectin administration during presensitization inhibits allergic
      response to ovalbumin in BALB/c mice.
AB  - OBJECTIVE: A type of respiratory disorder resembling some aspects of human
      allergic asthma can be induced in mice using ovalbumin. The factors that
      influence the etiology of asthma are poorly understood even though cytokines are
      known to play a pivotal role. The purpose of this study was to test the
      hypothesis whether an administration of Asian pear pectin during presensitization
      could suppress allergic response to ovalbumin in BALB/c mice. DESIGN: High-dose
      (100 microg) of pectin-sol was used and values were compared to those from the
      control. Ovalbumin and aluminum hydroxide were utilized for sensitization while
      ovalbumin aerosol was used for provocation 2 weeks later. The bronchoalveolar
      lavage (BAL) and assessment of tracheal smooth muscle responsiveness to
      electrical field stimulation or acetylcholine were performed 1 day after
      ovalbumin provocation. Two main cytokines of interferon (IFN)-gamma and
      interleukin (IL)-5, and serum immunoglobulin E (IgE) were assayed. SETTINGS:
      Laboratory of the Chosun University Medical School SUBJECT: Male BALB/c mice
      RESULTS: Antigen dose of 5 microg for sensitization generated TH1 type cytokines
      in the lungs with a high level of IFN-gamma and a low level of IL-5. In contrast,
      TH2 type cytokines were produced in splenocytes including a high level of IL-5
      and a low level of IFN-gamma. Asian pear pectin-sol administration during
      presensitization significantly inhibited (p < 0.05) sensitivity of airway smooth
      muscle to electrical field stimulation and acetylcholine. Further, IFN-gamma
      production significantly decreased (p < 0.05) in BAL fluids while it
      significantly increased (p < 0.05) in splenic cells. On the other hand, IL-5
      production significantly increased (p < 0.05) in BAL fluids while it was a
      significant decrease (p < 0.05) in splenic cells. For the histopathologic changes
      in the lung, pear pectin-sol recovered ovalbumin (OVA)-induced abnormal signs to
      an almost normal state. As a correlate, IgE production significantly decreased (p
      < 0.05) in pectin-sol-treated animals compared to the control. CONCLUSIONS: It is
      possible from these data that BALB/c mice have different susceptibilities to
      different doses of OVA regulated by pulmonary TH1 and TH2 type cytokines,
      independent of splenic TH1 and TH2 type cytokines production. These results also
      indicate that administration of Asian pear pectin-sol in presensitized mice
      suppresses allergic asthmatic reaction.

PMID- 15253859
TI  - Immunomodulatory effects of Premna tomentosa (L. Verbenaceae) extract in J 779
      macrophage cell cultures under chromate (VI)-induced immunosuppression.
AB  - OBJECTIVE: In the present study, the immunomodulatory effects of Premna tomentosa
      extract against chromate (VI)-induced toxicity was assessed in J 779 macrophage
      cell line. DESIGN: The cells were analyzed for cytotoxicity, phagocytosis,
      oxidant burst, antioxidant status, and cell proliferation. RESULT: Chromate
      treatment resulted in a significant increase in cytotoxicity and free radical
      production. Furthermore, there is a significant decrease in reduced glutathione
      (GSH) levels and glutathione peroxidase activity (GPx). There was an appreciable
      decrease in cell proliferation and phagocytosis by macrophages in the presence of
      chromate. However, pretreatment of the cells with P. tomentosa extract (500
      microg concentration), 30 minutes prior to chromate (VI) treatment resulted in a
      significant inhibition of chromate-induced cytotoxicity and reactive oxygen
      species production. The extract also restored the antioxidant status, cell
      proliferation, and phagocytosis similar to that of control cells. CONCLUSION: The
      results confirm the cytoprotective and immunomodulatory effects of the leaves of
      P. tomentosa and its possible usage in immunosuppressed conditions.

PMID- 15253860
TI  - Assessment of the protective potential of Premna tomentosa (L. Verbenaceae)
      extract on lipid profile and lipid-metabolizing enzymes in acetaminophen
      intoxicated rats.
AB  - OBJECTIVES: The liver is often damaged by environmental toxins, poor eating
      habits, alcohol and over-the-counter drug use that damage and weaken the liver,
      leading to important public health problems such as hepatitis, cirrhosis, and
      alcoholic liver diseases. It is cardinal to treat liver disorders, because it
      affects the biochemistry of the cell directly. Damage to the liver can be
      prevented by including a balanced diet that includes nutrients and herbs that
      support a healthy liver. Premna tomentosa (PT) is one such herbal drug used
      widely in India for the treatment of liver disorders, and we have already
      reported the hepatoprotective potential and antioxidant property of methanolic
      extract of PT leaves. Because injury to the liver can promote a variety of
      reactions with consequent effect on lipids, the present study was designed to
      elucidate the hypolipidemic effect of PT extract in acetaminophen (AA)-induced
      hepatotoxicity in rats. DESIGN AND SUBJECTS: Animals were pretreated with PT
      extract (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by
      AA (640 mg/kg, intraperitoneally). RESULTS: PT extract pretreatment significantly
      inhibited induced alterations in the levels of cholesterol, triglycerides, free
      fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes.
      CONCLUSIONS: The results indicate that PT extract improves lipid metabolism and
      has the potential for use in hepatic disorders.

PMID- 15253861
TI  - Medical pluralism in action? A case study of community pharmacies in
      Johannesburg, South Africa.
AB  - OBJECTIVES: The main aim of this study was to examine whether, and to what
      extent, community pharmacies have become sites for the practice of complementary
      and alternative medicine (CAM) as an example of "medical pluralism." METHODS:
      Qualitative as well as quantitative methods such as a telephone survey of all
      pharmacies in Johannesburg, observations, and in-depth interviews with
      pharmacists and CAM healers were used. RESULTS: The evidence presented in this
      paper, although based on a study of community pharmacies in Johannesburg only,
      can be interpreted as an indication of a general trend in urban areas in South
      Africa, that of involvement with CAM in the form of dispensing and sales of CAM
      products, provision of advice, and, in a few cases, employment of CAM
      practitioners to consult on their premises. Thus the two systems of CAM and
      allopathic medicine are being practiced within the same premises. However, the
      manner in which they operate, as portrayed in this study, is that of two separate
      systems existing in relative harmony side-by-side. CONCLUSION: Because of the
      constraints of the study, it is difficult to ascertain to what extent this is a
      first step toward the development of a more meaningful integration between the
      systems. It is much easier to demonstrate that this growth is driven by the
      pharmacists' response to the growing demand from the public and their readiness
      to seize the opportunity to expand their responsibilities and increase their
      profits. This is supported by the willingness of CAM healers to participate in
      the endeavor.

PMID- 15253862
TI  - Explanatory attributions of anxiety and recovery in a study of kava.
AB  - OBJECTIVE: A need exists to understand illness attribution and treatment beliefs
      among those seeking botanical treatment for anxiety. The objectives of this study
      are to evaluate explanatory beliefs about reasons for generalized anxiety
      disorder (GAD), and to evaluate the extent to which subjects thought different
      approaches might be most helpful, in a study of botanical treatment. DESIGN: Post
      hoc analysis of data from two similarly randomized controlled clinical trails.
      SETTING: Psychiatric research clinic in an academic medical center. SUBJECTS:
      Fifty-one (51) outpatients participating in two randomized, double-blinded,
      placebo-controlled trials of kava in GAD. INTERVENTIONS: Kava and placebo. MAIN
      OUTCOME MEASURES: Hamilton Anxiety Scale and Global Improvement Scale. RESULTS:
      Subjects thought their conditions were largely related to personality factors,
      stressful life experiences, or cognitive patterns. These beliefs correlated
      positively with treatment response, whereas endorsement of belief in an energy
      imbalance or biologic abnormality correlated negatively with improvement.
      CONCLUSION: Subjects felt more strongly that cognitive patterns, personality and
      stress were causative of their GAD and of greatest relevance to recovery.
      Biologic/genetic factors were somewhat relevant, whereas the importance of energy
      imbalance and spiritual/religious factors were minimal. When treating patients,
      it is important to consider the patient's belief systems regarding the disorder,
      as well as credibility of treatment.

PMID- 15253863
TI  - The use of dietary supplements by veterans with cancer.
AB  - OBJECTIVE: To study the patterns of dietary supplement use in veterans with
      cancer. DESIGN: Using a detailed questionnaire, a cross-sectional study was
      conducted to determine the patterns of dietary supplement use by patients with
      cancer. SETTING/LOCATION: The study was conducted at the Hematology/ Oncology
      Clinic at the VA Hospital in Cincinnati, OH. SUBJECTS: Patients with malignancy
      who were attending the above clinic and willing to participate and sign a consent
      form were enrolled in the study. OUTCOMES/MEASURES: The use of dietary
      supplements, the type, frequency, and reason for use was captured, along with the
      source of dietary supplements and perceived benefits. RESULTS: Two hundred (200)
      veterans were surveyed, with a median age of 68 years (36-82). The type of
      malignancy included cancer of the genitourinary system (39.5%), lung (19.5%),
      gastrointestinal tract (14.5%), hematologic system (16%), skin/head/neck (6.5%),
      and other (4%). One hundred and twenty-two patients (122) used dietary
      supplements (61%). Multivitamins were the most commonly used dietary supplement
      reported by 98 patients (80.3%), followed by mineral use by 52 patients (40.6%).
      Ten (10) patients used herbal supplements. Patients who were employed and
      patients with higher education were more likely to use dietary supplements.
      Different reasons were given for dietary supplement use and 74% of the users
      reported perceived benefits, such as improved overall health and energy. While
      38% of the patients did not disclose dietary supplement use to their physicians,
      37.8% of them learned about dietary supplements from their physicians and 25%
      obtained their dietary supplements from the VA hospital. CONCLUSION: The use of
      dietary supplements is common among veterans with cancer. Health care
      professionals should inquire about them in a systematic fashion and be prepared
      to provide counseling to their patients about them.

PMID- 15253865
TI  - Toward a binary interpretation of acupuncture theory: principles and practical
      consequences.
AB  - There is an argument that the universe functions according to binary principles.
      This paper applies such a system of evaluation to the interpretation of
      acupuncture principles, the t'ai chi symbol and the I Ching. As a result, it can
      be shown that a coherent and interesting ordering of some earthly phenomena can
      be reached. When these same principles are applied to acupuncture theory, a
      grouping and ordering of the meridians and associated organs and their respective
      functions are obtained. A suggestion is also presented about how, using a digital
      device, diagnosis and treatment could be reached in the future if this approach
      is deepened and proves successful. I call this binary medicine, something that
      would have some similarities as to how electroacupuncture according to Voll (EAV)
      works. Basically, diagnosis would be done in terms of excess, balance or deficit
      (+1, 0 or -1, respectively) and treatment would be done in terms of draining for
      +1 or filling for -1; 0 means a balanced state that does not need any treatment.

PMID- 15253864
TI  - Patient characteristics for outpatient acupuncture in Beijing, China.
AB  - OBJECTIVES: This study quantifies and compares patient characteristics in
      outpatient acupuncture. SETTING/DESIGN: Prospective primary source evidence was
      gathered at two prominent outpatient acupuncture clinics in Beijing, China (n =
      563, n = 233). RESULTS: The most common condition was Bell's palsy, which
      represented 20.6% and 25.3% of total cases at the two clinics, respectively. The
      second most common condition was cerebrovascular accident (CVA) rehabilitation.
      These treatments represented 11.9% and 12.0% of treatments at the two clinics,
      respectively. Other trends at the clinics included the following: (1) neurologic
      complaints predominated; (2) doctors see a large number of patients per day; (3)
      the majority of patients overall were female; while (4) the majority of patients
      treated for CVAs rehabilitation were male. As cultural and socioeconomic
      differences in perceptions of acupuncture exist between peoples of different
      countries, this study also compared patient main complaints in China to available
      data on acupuncture patients seen in other parts of China, Germany, the United
      Kingdom, Australia, and the United States. Except for the German clinic data,
      Western clinic acupuncturists saw more musculoskeletal complaints compared to
      China, where neurologic complaints predominated. Another significant difference
      between Asian and Western clinics was the number of patients seen per hour. While
      acupuncturists were reported to see 1.2 patients per hour in U. S. clinics,
      acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per
      hour, respectively. CONCLUSION: The main complaints seen in acupuncture
      outpatient clinics throughout the world likely result from a combination of
      inherent disease prevalence as well as patients' attitudes toward what
      acupuncture can treat successfully.

PMID- 15253866
TI  - One size does not fit all: aptitude x treatment interaction (ATI) as a conceptual
      framework for complementary and alternative medicine outcome research. Part 1-
      what is ATI research?
AB  - When multiple treatment choices are available, the question is not just "which
      treatment is the best?" but more importantly "best or better for whom, when, and
      why?" Aptitude (or attribute) by treatment interaction (ATI) is a research
      paradigm that attempts to examine exactly that--how outcome depends on the match
      or mismatch between patients' specific characteristics and the treatment they
      receive. The purpose of this two-part paper is to introduce ATI methods as a
      conceptual framework into complementary and alternative medicine/integrative
      medicine (CAM/IM) outcome research. Part 1 presents key concepts in ATI research.
      Part 2 will present ATI research designs and discusses their applications to the
      examination of the relationships between individuals and therapies, and the
      illumination of the mechanisms that make therapies differentially effective.
      Based on this examination, we conclude that ATI research offers invaluable
      insights into the multifaceted package of care typically delivered in
      contemporary medicine and therefore should be included in the portfolio of all
      CAM/IM outcome research.

PMID- 15253867
TI  - Exploring the evidence: the challenges of searching for research on acupuncture.
AB  - In complementary and alternative medicine, a number of basic problems exist for
      people who search for research-based information, one of which is the way that
      articles are indexed within the major databases. An exploration of the indexing
      of acupuncture studies was conducted as part of a review of research on the
      effectiveness of specific complementary therapies in cancer. Examination of
      several thesauri demonstrated variability in the terminology used for acupuncture
      and acupuncture-related therapies. Search strategies reported in published
      reviews also varied. Consequently, a series of acupuncture-related terms were
      used to search six major databases. The results provide an indication of the
      specificity and sensitivity of each term and also suggest which terms may be
      required for a relatively sensitive search for studies on the effectiveness of
      acupuncture therapy. A more detailed analysis of relevant research articles
      revealed a further issue for consideration--that of the variability in indexing
      by study type. While on MEDLINE randomized controlled trials are routinely
      identified as a specific publication type, on other databases and for other study
      types, the situation is less straightforward.

PMID- 15253868
TI  - Observations on the inherent variability of measuring lysozyme activity in coho
      salmon (Oncorhynchus kisutch).
AB  - Lysozyme activity is a common measurement of innate immunity. It has also been
      used to investigate genetic variation and an animal's responses to factors such
      as stress, infections and variations in diet. This research demonstrates the
      inherent variation in lysozyme activity in unstimulated coho salmon (Oncorhynchus
      kisutch). The role of maternal contribution, early life stage development and
      fish mass are considered. Genetic variation within and between strains of coho
      was found to be significant at selected life stages. Our results indicate that
      strain differences in lysozyme activity are more accurately measured by comparing
      the genetic variation after the eyed stage, when maternal effects are reduced. A
      positive correlation between plasma/serum lysozyme activity and fish mass is
      reported here. In summary, this study shows the role of maternal, developmental
      stage and size in lysozyme activity in fish, and emphasizes the importance of
      considering such variables when measuring the variability of lysozyme activity in
      fish.

PMID- 15253869
TI  - Sequence of horse (Equus caballus) apoA-II. Another example of a dimer forming
      apolipoprotein.
AB  - Apolipoprotein A-II, the second major apolipoprotein of human HDL, also has been
      observed in a variety of mammals; however, it is either present in trace amounts
      or absent in other mammals. In humans and chimpanzee, and probably in other great
      apes, apoA-II with a cysteine at residue 6 is able to form a homodimer. In other
      primates as well as other mammals, apoA-II, lacking a cysteine residue, is
      monomeric. However, horse HDL has been reported to contain dimeric apoA-II that
      following reduction forms monomers. In this report, we extend these observations
      by reporting on the first complete sequence for a horse apolipoprotein and by
      demonstrating that horse apoA-II also contains a cysteine residue at position 6.
      Both the intact protein and its enzymatic fragments were analyzed by chemical
      sequence analysis and time-of-flight MALDI-MS (matrix assisted laser desorption
      ionization mass spectrometry). We also obtained molecular mass data on dimeric
      and monomeric apoA-II using electrospray-ionization mass spectrometry (ESI-MS).
      The data are compared with other mammalian sequences of apoA-II and are discussed
      in terms of resulting similarities and variations in the primary sequences.

PMID- 15253870
TI  - Glycosylation of Rapana thomasiana hemocyanin. Comparison with other prosobranch
      (gastropod) hemocyanins.
AB  - The carbohydrate content and composition of hemocyanins (Hcs) of three
      prosobranchs (gastropods), Rapana thomasiana, Megathura crenulata and Haliotis
      tuberculata, were compared. The analyses were performed by gas-liquid
      chromatography after methanolysis, re-N-acetylation and trimethylsilylation. The
      two structural subunits of R. thomasiana Hc, RtH1 and RtH2, both showed 2.6%
      (w/w) carbohydrate content with very similar monosaccharide composition,
      indicative for N-glycosylation. The two isoforms of M. crenulata Hc (KLH), KLH1
      and KLH2, on the other hand, definitely differed in glycosylation: KLH2 (3.4%
      carbohydrate, w/w) comprised relatively less mannose and more N
      acetylgalactosamine than KLH1 (3.0% carbohydrate, w/w), in agreement with the
      fact that O-glycosylation has been observed in a functional unit (FU) of KLH2.
      For the Hc of the abalone H. tuberculata, with 4.5% (w/w) carbohydrate,
      appreciable amounts of 3-O-methyl-d-mannose and 3-O-methyl-d-galactose were
      detected, showing that the occurrence of methylated sugars is not restricted to
      the Hcs of pulmonates. From the structural subunit RtH2 of Rapana Hc the FUs RtH2
      b and RtH2-d were isolated. On the basis of amino acid sequence analysis and
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of the
      respective native and PNGase-F-treated glycopeptides, one N-glycosylation site
      was found for each FU. This site was located at Asn-405 for RtH2-b and at Asn-394
      for RtH2-d; the carbohydrate moiety corresponded to GlcNAc2Man6 and GlcNAc2Man5,
      respectively. A comparison was made with the N-glycosylation sites of other FUs
      of Rapana Hc.

PMID- 15253871
TI  - Carotenoid pigments and the selectivity of psittacofulvin-based coloration
      systems in parrots.
AB  - Carotenoid pigments are commonly used as colorants of feathers and bare parts by
      birds. However, parrots (Aves: Psittaciformes) use a novel class of plumage
      pigments (called psittacofulvins) that, like carotenoids, are lipid-soluble and
      red, orange, or yellow in color. To begin to understand how and why parrots use
      these pigments and not carotenoids in their feathers, we must first describe the
      distribution of these two types of pigments in the diet, tissues, and fluids of
      these birds. Here, we studied the carotenoid content of blood in five species of
      parrots with red in their plumage to see if they show the physiological ability
      to accumulate carotenoids in the body. Although Scarlet (Ara macao) and Greenwing
      Macaws (Ara chloroptera) and Eclectus (Eclectus roratus), African Gray (Psittacus
      erithacus) and Blue-fronted Amazon (Amazona aestiva) Parrots all use
      psittacofulvins to color their feathers red, we found that they also circulated
      high concentrations of both dietary (lutein, zeaxanthin, beta-cryptoxanthin) and
      metabolically derived (anhydrolutein, dehydrolutein) carotenoids through blood at
      the time of feather growth, at levels comparable to those found in many other
      carotenoid-colored birds. These results suggest that parrots have the potential
      to use carotenoids for plumage pigmentation, but preferentially avoid depositing
      them in feathers, which is likely under the control of the maturing feather
      follicle. As there is no evidence of psittacofulvins in parrot blood at the tune
      of feather growth, we presume that these pigments are locally synthesized by
      growing feathers within the follicular tissue.

PMID- 15253872
TI  - Cloning and expression of a pivotal calcium metabolism regulator: calmodulin
      involved in shell formation from pearl oyster (Pinctada fucata).
AB  - The shells of bivalves are mainly composed of calcium carbonate, a product of
      calcium metabolism. In the process of shell formation, the uptake, transport and
      recruitment of calcium ion are highly regulated and involved in many factors.
      Among these regulatory factors, calmodulin (CaM), a pivotal multifunction
      regulator of calcium metabolism in nearly all organisms, is thought to play an
      important role in the calcium metabolism involved in shell formation. In this
      study, a full-length CaM cDNA was isolated from the pearl oyster (Pinctada
      fucata). The oyster calmodulin encodes a 16.8 kDa protein which shares high
      similarity with vertebrate calmodulin. The oyster CaM mRNA shows the highest
      level of expression in the gill, a key organ involved in calcium uptake in oyster
      calcium metabolism. In situ hybridization results revealed that oyster CaM mRNA
      is expressed at the folds and the outer epithelial cells of the dorsal region of
      the mantle, suggesting that CaM is involved in regulation of calcium transport
      and secretion. Oyster CaM also showed a typical Ca2+ dependent electrophoretic
      shift characterization and calcium binding activity. Taken together, we have
      identified and characterized a pivotal calcium metabolism regulator of the oyster
      that may play an important role in regulation of calcium uptake, transport and
      secretion in the process of shell formation.

PMID- 15253873
TI  - Increase of uricogenesis in the kuruma shrimp Marsupenaeus japonicus reared under
      hyper-osmotic conditions.
AB  - Tissues of kuruma shrimp Marsupenaeus japonicus Bate (5.7+/-1.1 g) reared in
      salinities of 18, 26, 34 and 42 were examined for levels of nucleotide-related
      compounds, ammonia, urea and uric acid, and activities of xanthine dehydrogenase
      (XDH), xanthine oxidase (XOD) and uricase. Levels of total nucleotide-related
      compounds, including xanthine and hypoxanthine, in gill increased directly with
      salinity, whereas these same levels in hepatopancreas were inversely related with
      salinity. Hemolymph ammonia, urea and uric acid levels, and epidermal ammonia,
      urea and uric acid levels increased directly with salinity, whereas
      hepatopancreas ammonia and uric acid and gill uric acid levels were inversely
      related to salinity. Activities of XDH and XOD in hepatopancreas increased
      directly with salinity level, whereas no significant difference of uricase
      activity in hepatopancreas was observed among the four salinities. It is
      concluded M. japonicus exhibited uricogenesis and uricolysis, and an increase of
      uricogenesis occurred for the shrimp under hyper-osmotic conditions (salinity of
      42). Uric acid produced in the hepatopancreas was transported and accumulated in
      the epidermis, and removed along with the spongy connective tissue at the time of
      molting.

PMID- 15253874
TI  - Molecular cloning of multiple chitinase genes in Japanese flounder, Paralichthys
      olivaceus.
AB  - Three different chitinase genes (fChi1, fChi2 and fChi3) were identified from
      Japanese flounder, Paralichthys olivaceus. The deduced amino-acid sequences of
      flounder chitinases revealed a typical chitinase structure containing a catalytic
      glyco-18 domain, a hinge region and a chitin binding domain type 2. The fChi1 and
      fChi2 mRNAs were predominantly expressed in the gastric glands of stomach. In
      contrast, expression of fChi3 was found in spleen, pancreas, stomach, intestine,
      liver, kidney and gonads of adult flounder by RT-PCR. The expression level of
      fChi3 in the adult tissues was below the detection limit of in situ hybridization
      (ISH) analysis; however, ISH signals were detected in the liver of flounder
      larvae. These results suggest that fChi1 and fChi2 are acidic chitinases that
      digest dietary chitin and that fChi3 probably is a macrophage specific chitinase
      (chitotriosidase) for biodefense and has an important unknown role in the liver
      during larval stages.

PMID- 15253875
TI  - Methyl-branched hydrocarbons, major components of the waxy material coating the
      embryos of the viviparous cockroach Diploptera punctata.
AB  - The viviparous cockroach Diploptera punctata carries a wax-coated batch of
      embryos in a brood sac. When the embryos are expelled into saline, flakes of wax
      from the surface of the embryos float to the surface. In contrast, embryos of the
      ovoviviparous species such as Rhyparobia maderae are not nourished by the mother
      during embryogenesis and do not have a copious waxy coating. As a first step in
      determining the function of this copious wax layer on the batch of embryos of D.
      punctata, its composition was compared to that of the waxy material on the outer
      cuticular surface of the mother (female cuticle) by thin-layer chromatography
      (TLC) and gas chromatography-mass spectrometry. The major lipid class on the
      embryos was hydrocarbons with lesser amounts of wax esters and long-chain
      alcohols. Hydrocarbons from both sources had similar elution times and chemical
      composition, but were markedly different in the amounts of the major methyl
      branched hydrocarbon components. A mixture of 3,X-dimethyl alkanes were 44% of
      the hydrocarbons on the embryos and were only 29% on the female cuticle. However,
      trimethylalkanes were only 22% of the hydrocarbons on the embryos and were 34% of
      the hydrocarbons on the female cuticle. The major hydrocarbons from both sources
      were mixtures of methyl-branched alkanes with backbones of 33 and 35 carbon
      atoms. Methyl-branched tritriacontanes were 59% of embryo and 35% of female
      cuticular hydrocarbons; methyl-branched pentatriacontanes were 19% of embryo and
      42% of female hydrocarbons. The difference in proportions of the similar
      hydrocarbons on the outer cuticular surface of the female and those covering the
      embryos may suggest that the evolution of copious nutrient secretion for the
      embryos was accompanied by selection for a mixture of hydrocarbons that prevents
      water loss by the embryos and protects them against invasion by microorganisms
      without preventing the movement of nutrient fluid into the embryos.

PMID- 15253876
TI  - The rat kidney acylase 1. Evidence for a new cDNA form and comparisons with the
      porcine intestinal enzyme.
AB  - A new cDNA form encoding the rat kidney acylase I was characterized and found to
      show as much as 93.5% identity in its translated nucleotide sequence and, to a
      lesser extent, in its 3'-untranslated region with the nucleotide sequence we
      previously reported in 2000. Comparisons between the amino acid sequences of the
      two corresponding proteins showed the presence of N-terminal fragments with 88.5%
      identity and different cysteine profiles. The cDNA nucleotide sequence of the pig
      intestinal enzyme isolated from a marathon library turned out to be 100%
      identical to that of the kidney enzyme, but differed from those of the two rat
      kidney acylase I forms.

PMID- 15253877
TI  - Identification of a novel C1q family member in color crucian carp (Carassius
      auratus) ovary.
AB  - Potential roles of C1q/tumor necrosis factor (TNF) superfamily proteins have been
      observed in vertebrate oogenesis and oocyte maturation, but no ovary-specific
      member has been identified so far. In this study, we have cloned and identified a
      novel member of C1q family with a C1q domain in the C-terminal from fully grown
      oocyte cDNA library of color crucian carp and demonstrated that the gene might be
      specifically expressed in ovary and therefore designated as Carassius auratus
      ovary-specific C1q-like factor, CaOC1q-like factor. It encodes a 213 amino acid
      protein with a 17 amino acid signal peptide. There is only one protein band of
      about 24.5 kDa in the extracts from phase I to phase IV oocytes, but two positive
      protein bands are detected in the extracts of mature eggs and fertilized eggs.
      Furthermore, the mobility shift of the smaller target protein band cannot be
      eliminated by phosphatase treatment, but the larger protein band increases its
      mobility on the gel after phosphatase treatment, suggesting that the larger
      protein might be a phosphorylated form. Immunofluorescence localization indicates
      that the CaOC1q-like proteins localize in cytoplasm, cytoplasm membrane and egg
      envelope of the oocytes at cortical granule stage and vitellogenesis stage,
      whereas they were compressed to cytoplasm margin in ovulated mature eggs and
      discharged into perivitelline space between cytoplasm membrane and egg envelope
      after egg fertilization. Further studies on distribution and translocation
      mechanism of the CaOC1q-like factor will be benefit to elucidate the unique
      function in oogenesis, oocyte maturation and egg fertilization.

PMID- 15253878
TI  - The two subtype 1 somatostatin receptors of rainbow trout, Tsst1A and Tsst1B,
      possess both distinct and overlapping ligand binding and agonist-induced
      regulation features.
AB  - In the present study, two isoforms of somatostatin receptor subtype one,
      previously obtained from the brain of rainbow trout, Tsst1A and Tsst1B, were
      stably transfected in the Chinese hamster ovary cell line (CHO-K1) and their
      binding properties were characterized. High affinity binding of somatostatin by
      expressed receptors was saturable and ligand selective. Both Tsst1A and Tsst1B
      preferentially bound peptides derived from preprosomatostatin I (PPSS I; e.g., SS
      14-I) over those derived from PPSS II (containing Tyr7, Gly10-SS-14-I at their C
      terminus; e.g., SS-25-II). The rank order of ligand affinities for Tsst1A was SS
      28-I>SS-14-I>SS-26-I?SS-28-II>SS-14-II>SS-25-II. The rank order for Tsst1B was SS
      14-I>SS-28-I>SS-26-1?SS-28-II>SS-25-II>SS-14-II. Agonist-induced regulation of
      Tsst1A and Tsst1B was also investigated. After 30 min of SS-14-I exposure, both
      Tsst1A and Tsst1B underwent rapid internalization; ca. 60% of membrane Tsst1A was
      internalized and only about 40% of membrane Tsst1B was internalized. Prolonged
      agonist exposure (up to 48 h) induced up-regulation of membrane-expressed Tsst1A,
      but had no effect on Tsst1B. These results indicate that Tsst1s display both
      distinct and overlapping ligand binding and agonist-induced regulation features.
      Such features may form the basis of ligand-selection and have important
      consequences on target organ responsiveness.

PMID- 15253879
TI  - Purification of vitellin from the ovary of Chinese mitten-handed crab (Eriocheir
      sinensis) and development of an antivitellin ELISA.
AB  - Vitellin was purified from ovaries of mature female Chinese mitten-handed crab
      (Eriocheir sinensis) using gel filtration chromatography. Analysis by native PAGE
      showed the vitellin had a native molecular mass of 520 kDa, while denaturing SDS
      PAGE revealed two subunits of 97 and 74 kDa. Purified vitellin was used to raise
      polyclonal antisera, with which an enzyme-linked immunosorbent assay (ELISA) was
      developed. The ELISA was sensitive and could effectively detect vitellin in the
      range of 7.8-500 ng. Furthermore, vitellin levels in various developmental stages
      of oogenesis were measured with the ELISA assay. The results indicated that
      levels of vitellin increased significantly from 0.22 mg/ovary at Stage II to
      360.31 mg/ovary at Stage IV.

PMID- 15253880
TI  - Cuticular lipids and desiccation resistance in overwintering larvae of the
      goldenrod gall fly, Eurosta solidaginis (Diptera: Tephritidae).
AB  - Within their gall, larvae of the goldenrod gall fly (Eurosta solidaginis)
      experience severe desiccating conditions as well as highly variable thermal
      conditions and extreme cold during winter. Through the autumn and early winter,
      field-collected larvae acquired markedly enhanced resistance to desiccation and
      freezing. At the same time, they increased their cuticular surface hydrocarbons.
      Hydrocarbons were the major lipid class extracted by hexane or chloroform from
      the cuticular surface of overwintering gall fly larvae. The major hydrocarbon
      classes were the 2-methylalkanes which consisted mainly of 2-methyltriacontane. 2
      Methyltriacontane comprised 48-68% of the total hydrocarbons during the larval
      stages. Total hydrocarbons increased from 122 ng/larva in early third instar
      larvae collected in September to 4900 ng/larva in those collected in January.
      Although washing of the cuticular surface with chloroform or chloroform:methanol
      (2:1, v:v) caused marked increases in rates of water loss, treatment with hexane
      and methanol had little effect on water loss rates.

PMID- 15253881
TI  - The effect of the indomethacin on phosphodiesterase inhibitors mediated responses
      in isolated trachea preparations.
AB  - The aim of this study was to investigate the effects of indomethacin alone and
      with phosphodiesterase (PDE) inhibitory agents (rolipram, theophylline) on the
      isolated trachea preparations from control and ovalbumin sensitized guinea-pigs.
      Adult male guinea-pigs, weighing 300-350 g, were randomly allocated to 2
      experimental groups each consisting of 12 animals. Guinea-pigs were sensitized by
      i.m. injections of 0.35 ml of a 5% (w/v) ovalbumin/saline solution into each
      thigh (0.7 ml total) on days 1 and 4. Tissues were first contracted with a
      submaximal concentration of histamine (10(-6) M). We tested the effects of
      indomethacin (10(-7)-10(-4) M) on the resting tension and precontracted with
      histamine on the isolated trachea preparations from control and ovalbumin
      sensitized guinea-pigs. We also tested the effects of the rolipram, theophylline
      and isoproterenol isolated trachea preparations precontracted with histamine in
      indomethacin incubated or non-incubated groups. We found that the relaxant
      effects of rolipram and theophylline increased, but not of isoproterenol, in the
      presence of indomethacin in isolated trachea preparations precontracted from
      control and ovalbumin-sensitized guinea-pigs. In the presence of indomethacin
      there was no difference in relaxant responses between both groups. Therefore, we
      concluded that the increased relaxant responses may be due to inhibitor effect of
      this agent on PDE isoenzymes.

PMID- 15253882
TI  - Elevated urinary 8-isoprostaglandin F(2alpha) in females with Graves'
      hyperthyroidism.
AB  - In this study, we investigate how oxidative stress alters the urinary F2
      isoprostanes' level and we examine the correlation between 8-isoPGF(2alpha) and
      thyroid hormones in female patients with Graves' hyperthyroidism. We
      quantitatively determined the concentrations of urinary F2-isoprostanes using gas
      chromatography-mass spectrometry in the selected ion-monitoring mode. We
      recruited individuals in the following three groups of subjects for this study:
      (1) female hyperthyroidism patients (n = 14, 21-71 years), (2) female
      hypothyroidism patients (n = 16, 16-66 years), and (3) female age-matched normal
      controls (n = 10, 20-61 years). The average concentration of 8-iso prostaglandin
      F(2alpha) (8-isoPGF(2alpha)) in hyperthyroidism patients was significantly higher
      than that in the healthy controls (P < 0.05). The concentration of 8
      isoPGF(2alpha) in hypothyroidism patients was similar to that in normal controls.
      Although the level of 8-isoPGF(2alpha) in two of the patients was slightly
      elevated, the P value was not significant (NS). Our data suggest that the
      increased level of urinary 8-isoPGF(2alpha) may reflect possible oxidation
      injuries in hyperthyroidism patients due to the high level of thyroid hormones.
      Therefore, the elevated 8-isoPGF(2alpha) in patients could be used as an
      important biomarker for hyperthyroidism disease.

PMID- 15253883
TI  - Effect of fish oil supplementation on plasma oxidant/antioxidant status in rats.
AB  - The aim of this study was to investigate effect of dietary omega-3 fatty acid
      supplementation on the indices of in vivo lipid peroxidation and
      oxidant/antioxidant status of plasma in rats. The plasma thiobarbituric acid
      reactive substances (TBARS) and nitric oxide (NO) levels, and activities of
      xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GSH
      PX) were studied in male Wistar Albino rats after ingestion of 0.4 g/kg fish oil
      (rich in omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid) for
      30 days and compared to untreated control rats. The rats in the treated group had
      significantly higher SOD activity (P < 0.001), NO levels (P < 0.01) and decreased
      TBARS levels (P < 0.05) with respect to controls whereas GSH-Px and XO activities
      were not significantly different between the groups. None of the measured
      parameters had significant correlation with each other in both groups. We
      conclude that dietary supplementation of omega-3 fatty acids may enhance
      resistance to free radical attack and reduce lipid peroxidation. These results
      support the notion that omega-3 fatty acids may be effective dietary supplements
      in the management of various diseases in which oxidant/antioxidant defence
      mechanisms are decelerated.

PMID- 15253884
TI  - Can n-3 PUFA reduce cardiac arrhythmias? Results of a clinical trial.
AB  - Dietary n-3 polyunsaturated fatty acids (PUFA) derived from fatty fish or fish
      oil may reduce the incidence of lethal myocardial infarction and sudden cardiac
      death. This might be due to a prevention of fatal cardiac arrhythmias. So far,
      however, only few clinical data are available being adequate to define
      indications for an antiarrhythmic treatment with n-3 PUFA. In a randomized,
      double-blind, placebo-controlled study 65 patients with cardiac arrhythmias
      without coronary heart disease or heart failure were subdivided into 2 groups.
      One group (n = 33) was supplemented with encapsulated fish oil (3g/day,
      equivalent to 1g/day of n-3 PUFA) over 6 months. The other group (n = 32) was
      given 3g/day of olive oil as placebo. In the fish oil group a decrease of serum
      triglycerides, total cholesterol, LDL cholesterol, plasma free fatty acids and
      thromboxane B2 as well as an increase of HDL cholesterol were observed. Moreover,
      a reduced incidence of atrial and ventricular premature complexes, couplets and
      triplets were documented. Accordingly, higher grades of Lown's classification
      switched to lower grades at the end of the dietary period. No changes were seen
      in the placebo group. The data indicate an antiarrhythmic action of n-3 PUFA
      under conditions of clinical practice which might help to explain the reduced
      incidence of fatal myocardial infarction and sudden cardiac death in cohorts on a
      fish-rich diet or supplemented with n-3 PUFA. Further studies elucidating the
      possible link between the reduced incidence of cardiac arrhythmias and sudden
      cardiac death by dietary intake of n-3 PUFA are warranted.

PMID- 15253885
TI  - Brain phospholipases A2: a perspective on the history.
AB  - The phospholipases A2 (PLA2) belong to a large family of enzymes involved in the
      generation of several second messengers that play an important role in signal
      transduction processes associated with normal brain function. The phospholipase
      A2 family includes secretory phospholipase A2, cytosolic phospholipase A2,
      calcium-independent phospholipase A2, plasmalogen-selective phospholipase A2 and
      many other enzymes with phospholipase A2 activity that have not been classified.
      Few attempts have been made purify and characterize the multiple forms of PLA2
      and none have been fully characterized and cloned from brain tissue. A tight
      regulation of phospholipase A2 isozymes is necessary for maintaining
      physiological levels of free fatty acids including arachidonic acid and its
      metabolites in the various types of neural cells. Under normal conditions,
      phospholipase A2 isozymes may be involved in neurotransmitter release, long-term
      potentiation, growth and differentiation, and membrane repair. Under pathological
      conditions, high levels of lipid metabolites generated by phospholipase A2 are
      involved in neuroinflammation, oxidative stress, and neural cell injury.

PMID- 15253886
TI  - Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with
      schizophrenia.
AB  - Studies suggest that the omega-3 fatty acid supplementation may be beneficial in
      reducing symptom severity in schizophrenia. The mechanism(s) underlying the
      clinical effect is not known. Serotonin (5-HT) has been implicated in the
      pathophysiology of schizophrenia and in the mechanism of some antipsychotic
      agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We
      examined whether supplementation with the omega-3 fatty acid eicosapentaenoic
      acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients
      with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months
      supplementally to ongoing antipsychotic treatment in 12 patients with chronic
      schizophrenia, using an open-label design. Red blood cell membrane fatty acids
      and platelet functions (platelet aggregation and dense granule secretion) were
      monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more
      than five-fold in RBC membranes of all patients after 3 months supplementation,
      indicating a high degree of compliance. Consistent with previous reports, there
      was inhibition of ADP-induced platelet aggregation by EPA supplementation.
      Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the
      magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously,
      we have demonstrated a significant inverse correlation between 5-HT responsivity
      and psychosis severity in unmedicated patients with schizophrenia. Taken
      together, the present data support the notion that EPA may be mediating its
      therapeutic effects in schizophrenia via modulation of the 5-HT2 receptor
      complex.

PMID- 15253887
TI  - Monomodal rigid-body registration and applications to the investigation of the
      effects of eicosapentaenoic acid intervention in neuropsychiatric disorders.
AB  - The technique of monomodal rigid-body registration of serial magnetic resonance
      scans based on the sinc ((sin z)/z) interpolation function and its application to
      neuropsychiatric disorders, such as schizophrenia, depression and Huntington's
      disease, in relation to the assessment of the cerebral effects of intervention
      with the n-3 highly unsaturated fatty acid eicosapentaenoic acid are described.
      The evidence thus far indicates that researchers investigating the benefits of
      treatment with essential fatty acids in neuropsychiatric disorders should
      consider utilizing this technique.

PMID- 15253888
TI  - In vivo magnetic resonance spectroscopy in chronic fatigue syndrome.
AB  - The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not clearly
      known. Fatigue, poor short-term memory and muscle pain are the most disabling
      symptoms in CFS. Research data on magnetic resonance spectroscopy (MRS) of
      muscles and brain in CFS patients suggest a cellular metabolic abnormality in
      some cases. 31P MRS of skeletal muscles in a subset of patients indicate early
      intracellular acidosis in the exercising muscles. 1H MRS of the regional brain
      areas in CFS have shown increased peaks of choline derived from the cell membrane
      phospholipids. Cell membrane oxidative stress may offer a common explanation for
      the observed MRS changes in the muscles and brain of CFS patients and this may
      have important therapeutic implications. As a research tool, MRS may be used as
      an objective outcome measure in the intervention studies. In addition, regional
      brain 1H MRS has the potential for wider use to substantiate a clinical diagnosis
      of CFS from other disorders of unexplained chronic fatigue.

PMID- 15253889
TI  - Role of leukotrienes in killing of Mycobacterium bovis by neutrophils.
AB  - The neutrophil (PMN) plays an important role in the phagocytosis and killing of
      microorganisms. Pro-inflammatory leukotrienes (LT) play an important role in
      various disease states. However LT elaborated by PMN have also been shown to be
      important in host defense, specifically phagocytosis and killing of
      microorganisms. Defective LT synthesis by phagocytes correlates with their
      reduced anti-microbial activity. Therefore, we determined if LT played an
      important role in the killing of Mycobacteria bovis (M. bovis) by PMN. Endogenous
      LT play a role in the killing of mycobacteria since the LT synthesis inhibitor MK
      886 reversed the killing of M. bovis by PMN. Increased synthesis of LT occurred
      following incubation of PMN with M. bovis. Treatment with granulocyte-colony
      stimulating factor, which augments PMN LT synthesis, also boosted anti-microbial
      activity. Furthermore, exogenous LTB4 augmented dose-dependent killing of M.
      bovis by PMN. In conclusion, LT play a vital role in promoting mycobactericidal
      actions of PMN.

PMID- 15253890
TI  - Differential effects of serum constituents on apoptosis induced by the
      cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in WISH
      epithelial cells.
AB  - Cyclopentenone prostaglandins, delta12-PGJ2 and 15d-PGJ2, have potent anti-tumour
      and anti-inflammatory activities, and have been shown to induce apoptosis in
      amnion-derived WISH cells. In this study, we have investigated the protective
      effects of serum and its constituents (growth factors and albumin) on delta12
      PGJ2 and 15d-PGJ2-induced apoptosis in WISH cells. Serum (0.5% w/v) was
      protective against both delta12-PGJ2 and 15d-PGJ2-induced apoptosis. This was not
      due to the presence of serum-derived growth factors (EGF, IGF-1 and IGF-2), since
      they had no significant effect on 15d-PGJ2-induced cell death. In contrast, IGF-1
      partially inhibited etoposide-induced apoptosis, confirming the presence of a
      functional IGF-1 receptor signalling system. Albumin was identified as the key
      survival factor in serum, since albumin and delipidated albumin exhibited the
      same level of protection from 15d-PGJ2-induced apoptosis as serum itself. The
      potential for serum albumin to regulate the bioactivity of cyclopentenone PGs may
      be of considerable importance in pathological conditions where roles for
      cyclopentenone PGs have been identified.

PMID- 15253891
TI  - Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9
      apoptosome.
AB  - Cardiomyocyte apoptosis contributes to cell death during myocardial infarction.
      One of the factors that regulate the degree of apoptosis during ischemia is the
      amino acid taurine. To study the mechanism underlying the beneficial effect of
      taurine, we examined the interaction between taurine and mitochondria-mediated
      apoptosis using a simulated ischemia model with cultured rat neonatal
      cardiomyocytes sealed in closed flasks. Exposure to medium containing 20 mM
      taurine reduced the degree of apoptosis following periods of ischemia varying
      from 24 to 72 h. In the untreated group, simulated ischemia for 24 h led to
      mitochondrial depolarization accompanied by cytochrome c release. The apoptotic
      cascade was also activated, as evidenced by the activation of caspase-9 and -3.
      Taurine treatment had no effect on mitochondrial membrane potential and
      cytochrome c release; however, it inhibited ischemia-induced cleavage of caspase
      9 and -3. Taurine loading also suppressed the formation of the Apaf-1/caspase-9
      apoptosome and the interaction of caspase-9 with Apaf-1. These findings
      demonstrate that taurine effectively prevents myocardial ischemia-induced
      apoptosis by inhibiting the assembly of the Apaf-1/caspase-9 apoptosome.

PMID- 15253892
TI  - Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin
      1.
AB  - Psalmotoxin 1 (a component of the venom of a West Indies tarantula) is a 40-amino
      acid peptide that inhibits cation currents mediated by acid-sensing ion channels
      (ASIC). In this study we performed electrophysiological experiments to test the
      hypothesis that Psalmotoxin 1 (PcTX1) inhibits Na+ currents in high-grade human
      astrocytoma cells (glioblastoma multiforme, or GBM). In whole cell patch-clamped
      cultured GBM cells, the peptide toxin quickly and reversibly inhibited both
      inward and outward current with an IC50 of 36 +/- 2 pM. The same inhibition was
      observed in freshly resected GBM cells. However, when the same experiment was
      performed on normal human astrocytes, the toxin failed to inhibit the whole cell
      current. We also determined a cationic selectivity sequence for inward currents
      in three cultured GBM cell lines (SK-MG-1, U87-MG, and U251-MG). The selectivity
      sequence yielded a unique biophysical fingerprint with inward K+ conductance
      approximately fourfold greater than that of Na+, Li+, and Ca2+. These
      observations suggest that PcTX1 may prove useful in determining whether GBM cells
      express a specific ASIC-containing ion channel type that can serve as a target
      for both diagnostic and therapeutic treatments of aggressive malignant gliomas.

PMID- 15253893
TI  - The Na(+)-K(+)-ATPase alpha2-subunit isoform modulates contractility in the
      perinatal mouse diaphragm.
AB  - This study uses genetically altered mice to examine the contribution of the Na(+)
      K(+)-ATPase alpha2 catalytic subunit to resting potential, excitability, and
      contractility of the perinatal diaphragm. The alpha2 protein is reduced by 38% in
      alpha2-heterozygous and absent in alpha2-knockout mice, and alpha1-isoform is
      upregulated 1.9-fold in alpha2-knockout. Resting potentials are depolarized by
      0.8-4.0 mV in heterozygous and knockout mice. Action potential threshold,
      overshoot, and duration are normal. Spontaneous firing, a developmental function,
      is impaired in knockout diaphragm, but this does not compromise its ability to
      fire evoked action potential trains, the dominant mode of activation near birth.
      Maximum tetanic force, rate of activation, force-frequency and force-voltage
      relationships, and onset and magnitude of fatigue are not changed. The major
      phenotypic consequence of reduced alpha2 content is that relaxation from
      contraction is 1.7-fold faster. This finding reveals a distinct cellular role of
      the alpha2-isoform at a step after membrane excitation, which cannot be restored
      simply by increasing alpha1 content. Na+/Ca2+ exchanger expression decreases in
      parallel with alpha2-isoform, suggesting that Ca2+ extrusion is affected by the
      altered alpha2 genotype. There are no major compensatory changes in expression of
      sarcoplasmic reticulum Ca(2+)-ATPase, phospholamban, or plasma membrane Ca(2+)
      ATPase. These results demonstrate that the Na(+)-K(+)-ATPase alpha1-isoform alone
      is able to maintain equilibrium K+ and Na+ gradients and to substitute for alpha2
      isoform in most cellular functions related to excitability and force. They
      further indicate that the alpha2-isoform contributes significantly less at rest
      than expected from its proportional content but can modulate contractility during
      muscle contraction.

PMID- 15253894
TI  - Voluntary running induces fiber type-specific angiogenesis in mouse skeletal
      muscle.
AB  - Adult skeletal muscle undergoes adaptation in response to endurance exercise,
      including fast-to-slow fiber type transformation and enhanced angiogenesis. The
      purpose of this study was to determine the temporal and spatial changes in fiber
      type composition and capillary density in a mouse model of endurance training.
      Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately
      twofold increase in capillary density and capillary-to-fiber ratio in plantaris
      muscle as measured by indirect immunofluorescence with an antibody against the
      endothelial cell marker CD31 (466 +/- 16 capillaries/mm2 and 0.95 +/- 0.04
      capillaries/fiber in sedentary control mice vs. 909 +/- 55 capillaries/mm2 and
      1.70 +/- 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A
      significant increase in capillary-to-fiber ratio was present at day 7 with
      increased concentration of vascular endothelial growth factor (VEGF) in the
      muscle, before a significant increase in percentage of type IIa myofibers,
      suggesting that exercise-induced angiogenesis occurs first, followed by fiber
      type transformation. Further analysis with simultaneous staining of endothelial
      cells and isoforms of myosin heavy chains (MHCs) showed that the increase in
      capillary contact manifested transiently in type IIb + IId/x fibers at the time
      (day 7) of significant increase in total capillary density. These findings
      suggest that endurance training induces angiogenesis in a subpopulation of type
      IIb + IId/x fibers before switching to type IIa fibers.

PMID- 15253895
TI  - Evidence for stabilization of aquaporin-2 folding mutants by N-linked
      glycosylation in endoplasmic reticulum.
AB  - Aquaporin-2 (AQP2) is the vasopressin-sensitive water channel that regulates
      water reabsorption in the distal nephron collecting duct. Inherited AQP2
      mutations that disrupt folding lead to nephrogenic diabetes insipidus (NDI) by
      targeting newly synthesized protein for degradation in the endoplasmic reticulum
      (ER). During synthesis, a subset of wild-type (WT) AQP2 is covalently modified by
      N-linked glycosylation at residue Asn123. To investigate the affect of
      glycosylation, we expressed WT AQP2 and four NDI-related mutants in Xenopus
      laevis oocytes and compared stability of glycosylated and nonglycosylated
      isoforms. In all constructs, approximately 15-20% of newly synthesized AQP2 was
      covalently modified by N-linked glycosylation. At steady state, however, core
      glycosylated WT protein was nearly undetectable, whereas all mutants were found
      predominantly in the glycosylated form (60-70%). Pulse-chase metabolic labeling
      studies revealed that glycosylated isoforms of mutant AQP2 were significantly
      more stable than their nonglycosylated counterparts. For nonglycosylated
      isoforms, the half-life of WT AQP2 was significantly greater (>48 h) than that of
      mutant AQP2 (T126M 4.1 +/- 1.0 h, A147T 4.2 +/- 0.60 h, C181W 4.5 +/- 0.50 h,
      R187C 6.8 +/- 1.2 h). This is consistent with rapid turnover in the ER as
      previously reported. In contrast, the half-lives of mutant proteins containing N
      linked glycans were similar to WT (approximately 25 h), indicating that
      differences in steady-state glycosylation profiles are caused by increased
      stability of glycosylated mutant proteins. These results suggest that addition of
      a single N-linked oligosaccharide moiety can partially compensate for ER folding
      defects induced by disease-related mutations.

PMID- 15253896
TI  - Urban biosphere and society: partnership of cities--introduction.
AB  - This paper reports on issues of conservation, equitable use of resources, and the
      improvement of quality of life for all persons living in densely populated cites.
      Case studies are presented that examine UNESCO's concept of biosphere reserve,
      demonstrating the elasticity and usefulness of the concept as a way to promote
      global sustainability and governance on local, regional and global levels.

PMID- 15253897
TI  - Toward urban biosphere reserves.
AB  - The objective of this article is to outline the evolution in applying the
      biosphere reserve concept to urban areas and to present some of the potential
      benefits and possible difficulties in the design and management of urban
      biosphere reserves.

PMID- 15253898
TI  - Regreening the metropolis: pathways to more ecological cities: keynote address.
AB  - Eighty percent of the American population now lives in metropolitan regions whose
      geographic extent continues to expand even as many core cities and inner-tier
      suburbs lose middle-class populations, jobs, and tax base. Urban sprawl and the
      socioeconomic polarizing of metropolitan America have been fostered by public
      policies including (1) federal subsidies for new infrastructure on the urban
      fringe; (2) tax policies that favor home ownership over rental properties; (3)
      local zoning codes; and (4) federal and state neglect of older urban
      neighborhoods. In the face of diminished access to "nature" outside of
      metropolitan areas, locally based efforts to protect and restore greenspaces
      within urban areas seek to make older communities more habitable and more
      "ecological." Some pathways to more ecological cities include the following: (1)
      the notion of rus in urbe ("the country in the city"); (2) the "usable outdoors";
      (3) garden cities and eco-villages; (4) green buildings and green roofs; (5)
      urban biodiversity; (6) ecological services; and (7) space, nature, and place.

PMID- 15253899
TI  - Sustainable Cities Programme: a joint UN-HABITAT-UNEP facility on the urban
      environment with participation of the Dutch government.
AB  - The fundamental objective of the Sustainable Cities Programme is to promote
      environmentally sustainable local development to more fully realize the vital
      contributions that urban areas make to over-all social and economic development
      by: (1) enhancing efficiency in the use of local environmental resources,
      reducing environmental risks, and strengthening application of environmental
      conventions and agreements with growing regard to the Climate Change Protocol;
      (2) reducing poverty by promoting more equitable access to resources and
      environmental services; (3) mobilizing and strengthening local capacities to
      plan, co-ordinate, and manage sustainable local development in partnership; and
      (4) combining the complementary strengths of UN-HABITAT, UNEP, and other partners
      in support of Agenda 21, and the Habitat Agenda sustainable development
      commitments including improved local environmental governance.

PMID- 15253900
TI  - The UNESCO biosphere reserve concept as a tool for urban sustainability: the
      CUBES Cape Town case study.
AB  - The Cape Town Case Study (CTCS) was a multi-institutional collaborative project
      initiated by CUBES, a knowledge networking initiative of UNESCO's Ecological
      Sciences Division and the Earth Institute at Columbia University. Cape Town was
      selected as a CUBES site on the basis of its high biological and cultural
      significance, together with its demonstrated leadership in promoting urban
      sustainability. The CTCS was conducted by the Cape Town Urban Biosphere Group, a
      cross-disciplinary group of specialists drawn from national, provincial,
      municipal, and civil society institutions, mandated to examine the potential
      value of the UNESCO Biosphere Reserve concept as a tool for environmental
      management, social inclusion, and poverty alleviation in Cape Town. This article
      provides a contextualization of the CTCS and its collaborative process. It also
      reviews the biosphere reserve concept relative to urban sustainability objectives
      and proposes a more functional application of that concept in an urban context. A
      detailed analysis of key initiatives at the interface of conservation and poverty
      alleviation is provided in table format. Drawing on an examination of successful
      sustainability initiatives in Cape Town, specific recommendations are made for
      future application of the biosphere reserve concept in an urban context, as well
      as a model by which urban areas might affiliate with the UNESCO World Network of
      Biosphere Reserves, and criteria for such affiliation.

PMID- 15253901
TI  - Biodiversity, biosphere reserves, and the Big Apple: a study of the New York
      Metropolitan Region.
AB  - The objectives of this article were to assess the dimensions of biodiversity
      urban society interactions within the New York Metropolitan Region, a 31-county
      area with a population of 21.5 million, and to explore pathways to reconcile
      dysfunctional relationships between these two ever-entwined systems. The article
      builds on the premise that urban biodiversity exists at a crucial nexus of
      ecological and societal interactions, linking local, regional, and global scales,
      and that urban ecologies are projected to become even more dynamic in the future,
      particularly as a result of global climate change. The pathway proposed to
      reconcile the biodiversity-urban society relationships is the incorporation of
      biosphere reserve strategies into regional environmental planning efforts focused
      on the New York/New Jersey Harbor/Estuary specifically and on the greater New
      York Metropolitan Region in general. The concepts of the "ecological footprint"
      and vulnerability to global environmental change are used to analyze the current
      interactions between biodiversity and urban society, and to evaluate the efficacy
      of adopting biosphere reserve strategies in the region. New York has long been at
      the forefront of American environmentalism and landscape planning. Coupled with
      this history is a still small but growing interest in regional environmental
      planning efforts (e.g., the U.S. EPA Harbor Estuary Program) and green
      infrastructure (e.g., the 2002 Humane Metropolis Conference organized by the
      Ecological Cities Project). The research presented here aims to contribute to
      these nascent activities. As a megacity, New York may serve as a model for other
      major cities of the world.

PMID- 15253902
TI  - Managing the megacity for global sustainability: the new york metropolitan region
      as an urban biosphere reserve.
AB  - The UNESCO World Network of Biosphere Reserves (WNBR), while not originally
      conceived to include urban areas, was intended to include sites representing all
      significant ecosystems with the goal of support for sustainable development
      locally and globally. Drawing on the example of the New York Metropolitan Region
      (NYMR), which has a population of 21.4 million, it is argued here that the
      eventual inclusion of the largest of the world's cities in WNBR not only is
      within the logic of the biosphere reserve concept, but would also benefit the
      network and its goals. The ecological significance of the NYMR, its role as a
      driver for global environmental change, as well as the efforts under way in the
      city to improve urban environmental management and governance are all examined.
      Potential added value to the WNBR of including megacities such as the NYMR is
      considered, in particular, regarding the sharing of best practices, lessons
      learned, and the strengthening of links between megacities and their global
      natural resource bases.

PMID- 15253903
TI  - Improving air quality in megacities: Mexico City case study.
AB  - The development and effective implementation of solutions to the air pollution
      problems in the Mexico City Metropolitan Area is essential to guarantee the
      health and welfare of its inhabitants. To achieve this, it is essential to have
      the active and informed participation of the civil society, the academic
      community, the private sector, and the government, because dealing with pollution
      requires the use of different strategies in multiple fields of action. The Mexico
      City case study brings together health, transportation, administration, and many
      other interdisciplinary approaches to understanding and defeating air pollution.
      Although focused on the Mexico City area, the work conducted under this case
      study has significance for developing nations generally. Although policies to
      reduce air pollution should be based on the best available scientific knowledge,
      political will and capacity must transform this knowledge into action. This case
      study has developed a series of recommendations emphasizing the interaction
      between different disciplines that have provided the foundation for the 10-year
      air quality management program prepared by the Mexican Metropolitan Environmental
      Commission.

PMID- 15253904
TI  - Health in the urban environment: experience from Dar es Salaam/Tanzania.
AB  - Dar es Salaam is a typical example of the rapid urbanization process in sub
      Saharan Africa. Health problems in the city are tremendous and reflect the
      epidemiologic transition, with the emergence of chronic diseases, as well as the
      prevailing problems related to infectious diseases. Not surprisingly, HIV/AIDS
      has become a major determinant of health. Public health services have been
      strengthened in the past 12 years through the support of a bilateral program
      called the Dar es Salaam Urban Health Project (DUHP). The program was jointly
      funded by the Government of Tanzania and the Swiss Agency for Development and
      Cooperation. The focus of the program shifted from the initial rehabilitation of
      the health infrastructure to a strengthening of the management capacities of the
      public health care delivery system. The basis for the collaboration and
      complementarity between public and private health care providers has been
      created. Partly thanks to the success of the DUHP, the health system has become
      the spearhead and testing ground for core health sector reforms and has had a
      substantial influence on the introduction of a donor-supported sectorwide
      approach in the health sector in Tanzania. Perhaps most importantly, the
      foundations have been laid for a more democratic health system in which both the
      staff and the population are involved.

PMID- 15253905
TI  - Environmental factors in HIV/AIDS epidemic development: new perspectives for
      gender equity and global protection against HIV transmission.
AB  - The HIV/AIDS epidemic is increasingly regarded as a socioeconomic problem. Among
      factors causing poverty, cultural aspects, including religion and traditions,
      appear to play an essential role in the rapid and global development of AIDS
      epidemic. AIDS is a pathologic syndrome caused by the human immunodeficiency
      virus (HIV). Scientific knowledge is required to prevent and treat AIDS. Although
      considerable progress has been made in antiretroviral therapy, neither actual
      cure of HIV infection, nor an efficient protection method, nor a vaccine are
      currently globally accessible. Consequently, the funding of scientific research
      is of utmost importance. On the basis of recent scientific findings, new
      perspectives for global protection and gender equity against HIV transmission are
      emerging. Progress is being made in developing microbicides or virucides, anti
      infective medication formulated for topical self-administration, to protect
      against HIV and other sexually transmitted pathogens. Such developments need to
      be supported by extensive education campaigns geared to women to give them the
      possibility of protecting themselves and their children from HIV transmission.
      The level of funding for microbicide and vaccine development needs to be greatly
      increased. New possibilities have emerged for an efficient vaccine which would
      engage the mucosal immune system, first involved in the sexual transmission of
      HIV-1. The idea of vaccine production in edible tissues of transgenic crop plants
      has also gained momentum. The use of minimally processed, low-cost, orally
      delivered immunogens is especially valuable when raising mucosal antibodies is
      the object and when frequent boosting is anticipated, as is the case for mucosal
      immunity.

PMID- 15253906
TI  - Inhabitants' environmental perceptions in the city of Rome within the framework
      for urban biosphere reserves of the UNESCO programme on man and biosphere.
AB  - The article presents the main tenets of the UNESCO Programme on Man and Biosphere
      (MAB), launched by the United Nations at the beginning of the 1970s. The program
      aimed at supporting applied research and scientific knowledge for managing
      natural resources in a rational and sustainable way. The implication of the full
      ecological perspective, typical of the MAB, for promoting multidisciplinary and
      integrated approaches in the study of environmental issues is briefly outlined.
      In particular, we point out the role of the MAB, through the biosphere reserve
      concept, in supporting the collaboration between natural-biological and social
      behavioral sciences when dealing with biodiversity conservation problems and with
      urban ecosystems. Then, the specific UNESCO-MAB Project on the city of Rome,
      launched at the end of the 1980s, is briefly presented, together with the recent
      project of the Department of the Environment of the Rome Municipality to propose
      Rome's urban and periurban green areas as a new UNESCO-MAB Biosphere Reserve. The
      results of the main research activities conducted therein are summarized. In
      particular, the specific research lines of the environmental psychology research
      group, involved in the MAB-Rome Project for approximately two decades, are
      presented. These research lines dealt with various aspects of residents'
      environmental perceptions and behaviors in the city of Rome. The practical
      implications of these results are also briefly discussed.

PMID- 15253907
TI  - The application of the biosphere reserve concept to urban areas: the case of
      green rooftops for habitat network in Seoul.
AB  - This article consists of two parts. The first shows how the principles of the
      ecosystem approach can be applied to green rooftops, and the second attempts to
      illustrate it through a case study. In particular, it suggests new approaches and
      techniques for creation of green rooftops in a perspective of urban habitat
      network and urban biosphere reserve. To endow urban rooftops with the roles and
      functions of urban habitat network and urban biosphere reserve, it is necessary
      to apply "an ecosystem approach to urban management." In this article, an
      ecosystem approach to urban management is illustrated with Seoul as an example.
      The Habitat Network in Seoul will be reviewed with a focus on the model suggested
      by MAB Urban Group. Then, the roles and functions of Myeongdong UNESCO Green
      Rooftop and its possible contribution to building the Seoul Urban Biosphere
      Network will be described. The UNESCO Green Rooftop is 628 m(2) and was created
      on the 12th floor rooftop of UNESCO Building in Myeongdong 2-ga, Jung-ku, Seoul.
      In the green rooftop, which was created with goals of securing green areas and
      biotopes in downtown, creating an urban econetwork, securing a base for urban
      ecosystem study and environment education, and disseminating an idea of
      coexistence between nature and humankind, wetland, meadow, scrub and woodland,
      wall revegetation, and a vegetable field are created. Also, rainwater recycling
      facilities and a solar energy water circulation system were set up. Rest
      facilities including observation and education facilities were built. Based on
      the Seoul example, as well as urban biosphere reserve models suggested by the MAB
      Urban Group, we suggest several principles to be applied for a green rooftops to
      qualify as a category of urban biosphere reserves.

PMID- 15253908
TI  - Chicago wilderness: a new force in urban conservation.
AB  - In 1996, a coalition of diverse and determined organizations launched a new
      initiative in the Chicago region. Our vision? Chicago Wilderness: a thriving
      mosaic of natural areas, connected by greenways and wildlife corridors, embedded
      in the nation's third largest metropolis. In this vision, the region's human
      communities reclaim a cultural tradition of protecting and restoring the globally
      outstanding natural communities that enrich our lives. Today, more than 170
      organizations join forces to transform this vision into reality. A regional
      biodiversity recovery plan, the result of 3 years of assessment and planning by
      scientists, land managers, educators, and policy strategists, sets priorities and
      determines the lines of action for the coalition. This regional agenda stems from
      our vision and recovery goals for each ecological community; it encourages
      targeted research initiatives that focus on characterizing our native biological
      diversity and on analyzing elements critical to its recovery. Ultimately, though,
      the long-term survival of our natural wealth rests on the support from the
      public. Although the challenges to conservation educators and communicators are
      many, Chicago Wilderness allows us to work together in understanding our
      audiences, channeling our resources, and creating novel approaches to engage the
      widest public in our conservation efforts.

PMID- 15253909
TI  - Application of the biosphere reserve concept to urban areas: the case of Sao
      Paulo City Green Belt Biosphere Reserve, Brazil--Sao Paulo Forest Institute: a
      case study for UNESCO.
AB  - This report attempts to bring together contributions from technicians and
      scientists studying and dealing with the manifold aspects of the Sao Paulo City
      Green Belt Biosphere Reserve. It will highlight the understanding by UNESCO of
      the important role that biosphere reserves can play in the urban setting.

PMID- 15253910
TI  - Written in stone: memory and reconciliation intersecting the urban biosphere.
AB  - The article describes the process of planning the Memorial of Disappeared
      Detained Citizens in the City of Montevideo, Uruguay, the construction of which
      was completed in January 2003. It explores the role that memory, planning, and
      reconciliation carried out in the public realm can play in the context of an
      urban environment. It describes the procedures and involvement of different
      social agents in the achievement of a significant landmark where social healing
      is promoted in parallel to the materialization of the construction of the
      Memorial, the necessary interaction between the natural and the human dimensions,
      and how these relate to the city as a biosphere.

PMID- 15253911
TI  - Sustainability, survivability, and the paradox of New Orleans.
AB  - Some precepts of the urban sustainability movement derive from the premise that
      economic expansion, population growth, and physical sprawl lead to a decline in
      quality of life, ecological damage, and eventual unsustainability. But what about
      cities that are failing-losing population, losing investment, losing
      infrastructure, even losing land? This article challenges conventional
      sustainability concepts, usually derived from the experiences of ascending
      cities, with the notion of survivability that confronts declining cities. Should
      troubled cities, such as New Orleans, located on the eroding Gulf of Mexico
      coastal region of the state of Louisiana, be held to different sustainability
      standards? Could urban expansion, in some cases, actually stem environmental
      degradation and enhance survivability?

PMID- 15253912
TI  - Governance challenges and coalition building among urban environmental
      stakeholders in Dar es Salaam, Tanzania.
AB  - Rapid urbanization is arguably one of the most complex and important
      socioeconomic phenomena of the new millennium. It represents major and
      irreversible changes in production and consumption patterns and the way people
      interact with nature. The impact of urbanization will continue to bring about
      major changes especially in many countries in the developing world that are
      experiencing rapid urbanization. The serious environmental and development
      challenges facing Dar es Salaam, the largest commercial center of Tanzania, are
      highlighted in this report.

PMID- 15253913
TI  - The dynamics of social-ecological systems in urban landscapes: Stockholm and the
      National Urban Park, Sweden.
AB  - This study addresses social-ecological dynamics in the greater metropolitan area
      of Stockholm County, Sweden, with special focus on the National Urban Park (NUP).
      It is part of the Millennium Ecosystem Assessment (MA) and has the following
      specific objectives: (1) to provide scientific information on biodiversity
      patterns, ecosystem dynamics, and ecosystem services generated; (2) to map
      interplay between actors and institutions involved in management of ecosystem
      services; and (3) to identify strategies for strengthening social-ecological
      resilience. The green areas in Stockholm County deliver numerous ecosystem
      services, for example, air filtration, regulation of microclimate, noise
      reduction, surface water drainage, recreational and cultural values, nutrient
      retention, and pollination and seed dispersal. Recreation is among the most
      important services and NUP, for example, has more than 15 million visitors per
      year. More than 65 organizations representing 175,000 members are involved in
      management of ecosystem services. However, because of population increase and
      urban growth during the last three decades, the region displays a quite dramatic
      loss of green areas and biodiversity. An important future focus is how management
      may reduce increasing isolation of urban green areas and enhance connectivity.
      Comanagement should be considered where locally managed green space may function
      as buffer zones and for management of weak links that connect larger green areas;
      for example, there are three such areas around NUP identified. Preliminary
      results indicate that areas of informal management represent centers on which to
      base adaptive comanagement, with the potential to strengthen biodiversity
      management and resilience in the landscape.

PMID- 15253914
TI  - The changing perception of the wetlands in and around Kristianstad, Sweden: from
      Waterlogged areas toward a future Water Kingdom, Kristianstads Vattenrike
      Biosphere Reserve.
AB  - Kristianstads Vattenrike (The Rich Wetlands of Kristianstad/Water Kingdom) is a
      35-km-long wetland area surrounded by cultivated landscape in the south of
      Sweden. The project area covers some more than 100,000 hectares and includes the
      lower catchment areas of River Helge a and the coastal areas of the bay
      Hanobukten, a part of the Baltic Sea. The River Helge a flows from upstream
      forests through agricultural land, lowland lakes, and wetlands and passes
      straight through the town of Kristianstad, which is the regional capital. An MAB
      candidate office is now in the process of completing the application form to
      become a biosphere reserve according to the UNESCO-MAB concept, but in the past
      the wetlands often were seen as waterlogged areas, especially in the 19th
      century.

PMID- 15253915
TI  - Sustainable energy planning with efficient office buildings and cogeneration
      plants in Frankfurt am Main.
AB  - Sustainable development of a city not only is determined through the amount of
      protected areas, but it is also an important task to integrate sustainable
      development in urban energy planning. In the last 10 years, many new areas for
      offices and residential buildings have been developed in Frankfurt am Main. In
      this context, the municipality has taken over a new role as organizer for the
      integrated energy planning. This article gives an overview of the achievements.

PMID- 15253916
TI  - Common interests and common goals: achieving greater progress in preventive
      health through strategic collaborations.

PMID- 15253917
TI  - Preventing cancer, cardiovascular disease, and diabetes: a common agenda for
      theAmerican Cancer Society, the American Diabetes Association, and the American
      Heart Association.
AB  - Collectively, cardiovascular disease (including stroke), cancer, and diabetes
      account for approximately two-thirds of all deaths in the United States and about
      700 billion US dollars in direct and indirect economic costs each year. Current
      approaches to health promotion and prevention of cardiovascular disease, cancer,
      and diabetes do not approach the potential of the existing state of knowledge. A
      concerted effort to increase application of public health and clinical
      interventions of known efficacy to reduce prevalence of tobacco use, poor diet,
      and insufficient physical activity-the major risk factors for these diseases-and
      to increase utilization of screening tests for their early detection could
      substantially reduce the human and economic cost of these diseases. In this
      article, the American Cancer Society, the American Diabetes Association, and the
      American Heart Association review strategies for the prevention and early
      detection of cancer, cardiovascular disease, and diabetes, as the beginning of a
      new collaboration among the three organizations. The goal of this joint venture
      is to stimulate substantial improvements in primary prevention and early
      detection through collaboration between key organizations, greater public
      awareness about healthy lifestyles, legislative action that results in more
      funding for and access to primary prevention programs and research, and
      reconsideration of the concept of the periodic medical checkup as an effective
      platform for prevention, early detection, and treatment.

PMID- 15253918
TI  - Long-term complications following childhood and adolescent cancer: foundations
      for providing risk-based health care for survivors.
AB  - Survivors of childhood and adolescent cancer are one of the higher risk
      populations seen by health care professionals. The curative therapy administered
      for the cancer also affects growing and developing tissues. Following
      chemotherapy, radiation therapy, and surgery, many survivors will experience
      chronic or late-occurring health problems, often not becoming clinically apparent
      until decades after therapy. Survivors face an increased risk of morbidity,
      mortality, and diminished quality of life associated with their previous cancer
      therapy. Risk is further modified by the survivor's genetics, lifestyle habits,
      and comorbid health conditions. Over their lifetime, survivors will see health
      care professionals from an array of specialties and disciplines. The aim of this
      review is threefold: (1) to convey a sense of the risk faced by survivors to
      clinicians unfamiliar with the population; (2) to provide an up-to-date tool for
      clinicians, regardless of specialty or discipline, when providing care for a
      survivor; and (3) to complement the recently completed recommendations for
      screening, prevention, and management of childhood cancer survivors.

PMID- 15253919
TI  - Infertility among male UK veterans of the 1990-1 Gulf war: reproductive cohort
      study.
AB  - OBJECTIVES: To examine the hypothesis that, theoretically at least, exposure to
      toxicants of the type present in the Gulf war could affect spermatogenesis, which
      might be observed as increased levels of infertility. DESIGN: Retrospective
      reproductive cohort analysis. SETTING: Male UK Gulf war veterans and matched
      comparison group of non-deployed servicemen, surveyed by postal questionnaire.
      PARTICIPANTS: 42,818 completed questionnaires were returned, representing
      response rates of 53% for Gulf veterans and 42% for non-Gulf veterans; 10,465
      Gulf veterans and 7376 non-Gulf veterans reported fathering or trying to father
      pregnancies after the Gulf war. MAIN OUTCOME MEASURES: Failure to achieve
      conceptions (type I infertility) or live births (type II infertility) after the
      Gulf war, having tried for at least a year and consulted a doctor; time to
      conception among pregnancies fathered by men not reporting fertility problems.
      RESULTS: Risk of reported infertility was higher among Gulf war veterans than
      among non-Gulf veterans (odds ratio for type I infertility 1.41, 95% confidence
      interval 1.05 to 1.89; type II 1.50, 1.18 to 1.89). This small effect was
      constant over time since the war and was observed whether or not the men had
      fathered pregnancies before the war. Results were similar when analyses were
      restricted to clinically confirmed diagnoses. Pregnancies fathered by Gulf
      veterans not reporting fertility problems also took longer to conceive (odds
      ratio for > 1 year 1.18, 1.04 to 1.34). CONCLUSIONS: We found some evidence of an
      association between Gulf war service and reported infertility. Pregnancies
      fathered by Gulf veterans with no fertility problems also reportedly took longer
      to conceive.

PMID- 15253920
TI  - Randomised controlled trial of pelvic floor muscle training during pregnancy.
AB  - OBJECTIVES: To examine a possible effect on labour of training the muscles of the
      pelvic floor during pregnancy. DESIGN: Randomised controlled trial. SETTING:
      Trondheim University Hospital and three outpatient physiotherapy clinics in a
      primary care setting. PARTICIPANTS: 301 healthy nulliparous women randomly
      allocated to a training group (148) or a control group (153). INTERVENTION: A
      structured training programme with exercises for the pelvic floor muscles between
      the 20th and 36th week of pregnancy. MAIN OUTCOME MEASURES: Duration of the
      second stage of labour and number of deliveries lasting longer than 60 minutes of
      active pushing among women with spontaneous start of labour after 37 weeks of
      pregnancy with a singleton fetus in cephalic position. RESULTS: Women randomised
      to pelvic floor muscle training had a lower rate of prolonged second stage labour
      (24%, 95% confidence interval 16% to 33%; 22 out of 105 women were at risk
      (undelivered) at 60 minutes in the survival analysis) than women allocated to no
      training (38% (37/109), 28% to 47%). The duration of the second stage was not
      significantly shorter (40 minutes v 45 minutes, P = 0. 06). CONCLUSIONS: A
      structured training programme for the pelvic floor muscles is associated with
      fewer cases of active pushing in the second stage of labour lasting longer than
      60 minutes.

PMID- 15253921
TI  - Bovine blastocyst development in vitro: timing, sex, and viability following
      vitrification.
AB  - Selection of blastocysts based on their morphological characteristics and rate of
      development in vitro can skew the sex ratios. The aim of this study was to
      determine whether an embryo's developmental rate affects its survival after
      vitrification, and whether male and female embryos survive vitrification
      differently. In vitro fertilized bovine oocytes were cultured in potassium
      simplex optimized medium (KSOM) + 0.1% BSA for 96 h, and then into KSOM + 1% BSA
      (KSOM) or in sequential KSOM + 0.1% BSA for 96 h, and then into synthetic oviduct
      fluid (SOF) + 5% FBS (KSOM-SOF). In part 1 of this study, embryos cultured in
      each medium that had developed into blastocysts at approximately 144, 156, or 180
      h were recovered from culture, graded, and then vitrified. After warming,
      blastocyst survival rates were immediately evaluated by reexpansion of the
      blastocoels. In the second part of the study, all blastocysts (n = 191) were
      sexed by polymerase chain reaction 48 h after warming. When cultured in KSOM
      medium, more 144-h blastocysts survived vitrification (68%) than blastocysts
      vitrified at 180 h (49%). Blastocysts derived at 156 h in KSOM-SOF survived
      vitrification better (87%) than blastocysts vitrified at either 144 h or 180 h,
      and subsequently hatched at a greater rate than those vitrified at 180 h. The
      overall blastocyst survival rates did not differ significantly whether embryos
      were cultured in KSOM or sequential KSOM-SOF. Blastocysts derived at 144 and 156
      h in KSOM or KSOM-SOF were predominately male, and significantly more of them
      survived vitrification 48 h after warming. However, blastocysts cultured in KSOM
      SOF, and then vitrified at 180 h were predominately female. Overall, blastocysts
      that survived vitrification, and subsequently hatched 48 h after warming, were
      male. In summary, embryos that reached the blastocyst stage earlier were
      predominantly males; these males had better morphology, endured vitrification,
      and subsequently hatched at a greater rate than did female blastocysts.

PMID- 15253923
TI  - Testicular phenotype in luteinizing hormone receptor knockout animals and the
      effect of testosterone replacement therapy.
AB  - The LH receptor knockout model, developed in our laboratory, was used in
      determining what FSH alone can do in the absence of LH signaling and whether any
      of the testicular LH actions are not mediated by androgens. The results revealed
      that null animals contained smaller seminiferous tubules, which contained the
      same number of Sertoli cells, spermatogonia, and early spermatocytes as wild-type
      siblings. The number of late spermatocytes, on the other hand, was moderately
      decreased, the number of round spermatids was dramatically decreased, and
      elongated spermatids were completely absent. These changes appear to be due to an
      increase in apoptosis in spermatocytes. While the number of Leydig cells
      progressively increased from birth to 60 days of age in wild-type animals, they
      remained unchanged in null animals. Consequently, 60-day-old null animals
      contained only a few Leydig cells of fetal type. The age-dependent increase in
      testicular macrophages lagged behind in null animals compared with wild-type
      siblings. Orchidopexy indicated that -/- testicular phenotype was not due to
      abdominal location. Rather, it was mostly due to androgen deficiency, as 21-day
      testosterone replacement therapy stimulated the growth of seminiferous tubules,
      decreased apoptosis, and increased the number of late spermatocytes and round
      spermatids and their subsequent differentiation into mature sperm. The therapy,
      however, failed to restore adult-type Leydig cells and testicular macrophage
      numbers to the wild-type levels. In summary, our data support the concept that
      FSH signaling alone can maintain the proliferation and development of Sertoli
      cells, spermatogonia, and early spermatocytes. LH actions mediated by
      testosterone are required for completion of spermatogenesis, and finally,
      androgen-independent actions of LH are required for the formation of adult-type
      Leydig cells and recruitment of macrophages into the testes.

PMID- 15253924
TI  - Train A, an RNase A-like protein without RNase activity, is secreted and
      reabsorbed by the same epididymal cells under testicular control.
AB  - Most of the proteins secreted in the epididymis are produced by the proximal
      region, and several of them are secreted in abundance. Many of these major
      proteins have now been identified, including a new epididymis-specific RNase A
      like Train A protein, which has been recently described in several mammals. This
      protein is expressed and secreted exclusively in the initial part of the
      epididymis. RNase A activity was analyzed in the fluids from the testis and from
      different epididymal regions, but in no case was the Train A protein found to
      have RNase A activity. The protein was present only in the luminal fluid of the
      epididymal region that secreted it. Using an in vitro/in vivo microperfusion
      technique and immunogold electron microscopy labeling, we demonstrated that the
      epithelium that secreted it specifically reabsorbed the protein that was present
      in the lumen of the tubule. Thus, the presence of Train A protein in epididymal
      fluid was the result of a steady state between secretion and absorption. The
      transcription and translation of Train A mRNA were simultaneous and actively
      regulated by testicular factors. The function of this protein is unknown, but it
      does not seem to interact directly with sperm. As for other members of the RNase
      family (e.g., angiogenin), its biological activity might be expressed after its
      cellular reabsorption. This new compound might therefore participate in an
      unknown function in the epithelial cells of this first part of the epididymis by
      an autocrine pathway.

PMID- 15253925
TI  - Insulin-like growth factor-I as a survival factor for the bovine preimplantation
      embryo exposed to heat shock.
AB  - Insulin-like growth factor-I (IGF-I) is a survival factor for preimplantation
      mammalian embryos exposed to stress. One stress that compromises preimplantation
      embryonic development is elevated temperature (i.e., heat shock). Using bovine
      embryos produced in vitro as a model, it was hypothesized that IGF-I would
      protect preimplantation embryos by reducing the effects of heat shock on total
      cell number, the proportion of blastomeres that undergo apoptosis, and the
      percentage of embryos developing to the blastocyst stage. In experiment 1,
      embryos were cultured with or without IGF-I; on Day 5 after insemination, embryos
      >or=16 cells were cultured at 38.5 degrees C for 24 h or were subjected to 41
      degrees C for 9 h followed by 38.5 degrees C for 15 h. Heat shock reduced the
      total cell number at 24 h after initiation of heat shock and increased the
      percentage of blastomeres that were apoptotic. Effects of heat shock were less
      for IGF-I-treated embryos. Experiment 2 was conducted similarly except that
      embryos were allowed to develop to Day 8 after insemination. The percentage
      reduction in blastocyst development for heat-shocked embryos compared with those
      maintained at 38.5 degrees C was less for embryos cultured with IGF-I than for
      control embryos. Heat shock reduced the total cell number in blastocysts and
      increased the percentage of blastomeres that were apoptotic, whereas IGF-I
      treated embryos had increased total cell number and a reduced percentage of
      apoptosis. Taken together, these results demonstrate that IGF-I can serve as a
      survival factor for preimplantation bovine embryos exposed to heat shock by
      reducing the effects of heat shock on development and apoptosis.

PMID- 15253926
TI  - Possible role of interleukin-1 in the regulation of bovine corpus luteum
      throughout the luteal phase.
AB  - Interleukin-1 (IL-1) is one of the principal cytokines that participate in local
      regulation of many reproductive functions. The present study was undertaken to
      determine whether mRNAs for IL-1alpha, IL-1beta, and IL-1 type I receptor (IL-1R)
      are expressed in bovine corpora lutea (CL), and whether luteal cells respond to
      treatment with IL-1alpha and IL-1beta during the luteal phase. Bovine CL were
      classified into five stages (early, Days 2-3; developing, Days 5-6; mid, Days 8
      12; late, Days 15-17; and regressed, Days 19-21). IL-1alpha, IL-1beta, and IL-1R
      mRNAs were detected by reverse transcription-polymerase chain reaction (PCR) in
      all luteal stages examined. Densitometric analysis of PCR products revealed
      increases of the mRNA of IL-1alpha and IL-1R in the CL of the regressed stage (P
      < 0.05). There was less mRNA for IL-1beta in the regressed stage than in the
      developing and mid stages (P < 0.05). When developing, mid, and late luteal cells
      were treated with IL-1alpha (1-30 ng/ml) or IL-1beta (1-30 ng/ml) for 24 h, IL
      1alpha and IL-1beta dose-dependently increased prostaglandin (PG) F(2alpha) and
      PGE(2) production by the luteal cells of all stages (P < 0.05), indicating the
      presence of functional IL-1R in bovine CL. However, progesterone synthesis was
      not affected by either IL-1alpha or IL-1beta treatment. Stimulation with IL
      1alpha and IL-1beta decreased the PGE(2):PGF(2alpha) ratio in the developing
      stage (P < 0.05), whereas it increased the ratio in the mid stage (P < 0.05). In
      the late stage, the ratio of IL-1beta-treated cells was greater than that of IL
      1alpha-treated cells (P < 0.05). Overall results indicate that genes for IL
      1alpha and IL-1beta are expressed and a functional IL-1R is present in the bovine
      CL throughout the luteal phase, and suggest that IL-1alpha and IL-1beta have
      different roles as local modulators to regulate PGF(2alpha) and PGE(2) production
      during the luteal phase.

PMID- 15253927
TI  - Proteasomal interference prevents zona pellucida penetration and fertilization in
      mammals.
AB  - The ubiquitin-proteasome pathway has been implicated in the penetration of
      ascidian vitelline envelope by the fertilizing spermatozoon (Sawada et al., Proc
      Natl Acad Sci U S A 2002; 99:1223-1228). The present study provides experimental
      evidence demonstrating proteasome involvement in the penetration of mammalian
      zona pellucida (ZP). Using porcine in vitro fertilization as a model, penetration
      of ZP was completely inhibited by specific proteasomal inhibitors MG-132 and
      lactacystin. Three commercial rabbit sera recognizing 20S proteasomal core
      subunits beta-1i, beta-2i, alpha-6, and beta-5 completely blocked fertilization
      at a very low concentration (i.e., diluted 1/2000 to 1/8000 in fertilization
      medium). Neither proteasome inhibitors nor antibodies had any effects on sperm-ZP
      binding and acrosome exocytosis in zona-enclosed oocytes or on fertilization
      rates in zona-free oocytes, which were highly polyspermic. Consistent with a
      possible role of ubiquitin-proteasome pathway in ZP penetration, ubiquitin and
      various alpha and beta type proteasomal subunits were detected in boar sperm
      acrosome by specific antibodies, immunoprecipitated and microsequenced by MALDI
      TOF from boar sperm extracts. Antiubiquitin-immunoreactive substrates were
      detected on the outer face of ZP by epifluorescence microscopy. This study
      therefore provides strong evidence implicating the ubiquitin-proteasome pathway
      in mammalian fertilization and zona penetration. This finding opens a new line of
      acrosome/ZP research because further studies of the sperm acrosomal proteasome
      can provide new tools for the management of polyspermia during in vitro
      fertilization and identify new targets for contraceptive development.

PMID- 15253928
TI  - Influence of lactation parameters on the N-glycosylation of recombinant human C1
      inhibitor isolated from the milk of transgenic rabbits.
AB  - The large-scale production of recombinant biopharmaceutical glycoproteins in the
      milk of transgenic animals is becoming more widespread. However, in comparison
      with bacterial, plant cell, or cell culture production systems, little is known
      about the glycosylation machinery of the mammary gland, and hence on the
      glycosylation of recombinant glycoproteins produced in transgenic animals. Here
      the influence is presented of several lactation parameters on the N-glycosylation
      of recombinant C1 inhibitor (rhC1INH), a human serum glycoprotein, expressed in
      the milk of transgenic rabbits. Enzymatically released N-glycans of series of
      rhC1INH samples were fluorescently labeled and fractionated by HPLC. The major N
      glycan structures on rhC1INH of pooled rabbit milk were similar to those on
      native human C1 inhibitor and recombinant human C1 inhibitor produced in
      transgenic mouse milk, with only the degree of sialylation and core fucosylation
      being lower. Analyses of individual animals furthermore showed slight
      interindividual differences; a decrease in the extent of sialylation, core
      fucosylation, and oligomannose-type glycosylation with the progress of lactation;
      and a positive correlation between expression level and oligomannose-type N
      glycan content. However, when large quantities of rhC1INH were isolated for
      preclinical and clinical studies, highly consistent N-linked glycan profiles and
      monosaccharide compositions were found.

PMID- 15253929
TI  - Isolation and characterization of a heparin with high anticoagulant activity from
      the clam Tapes phylippinarum: evidence for the presence of a high content of
      antithrombin III binding site.
AB  - Heparin with high anticoagulant activity (activated partial thromboplastin time
      of 347 +/- 56.4 and anti-Xa activity of 317 +/- 48.3) was isolated from the
      marine clam species Tapes phylippinarum in an amount of approximately 2.1 mg/g
      dry animals. Agarose-gel electrophoresis showed a high content of the slow-moving
      heparin component (22 +/- 6.8%) and 78 +/- 5.4% of the fast-moving species. An
      average molecular mass of 13,600 was calculated by PAGE analysis, whereas a
      number average molecular weight Mn value of 10,700, a weight average molecular
      weight Mw of 14,900, and a dispersity index Mn/Mw of 1.386 were obtained by high
      performance size-exclusion chromatography. Structural analysis of clam heparin,
      performed by depolymerizing heparin samples with heparinase (EC 4.2.2.7) and then
      separating the resulting unsaturated oligosaccharides by strong anion exchange
      HPLC revealed the presence of large amounts (more than 130% than standard
      pharmaceutical heparin obtained from bovine intestine) of the oligosaccharide
      sequence bearing part of the ATIII-binding region, DeltaUA2S (1-->4)-alpha-D
      GlcN2S6S (1-->4)-alpha-L-IdoA (1-->4)-alpha-D-GlcNAc6S (1-->4)-beta-D-GlcA (1-
      >4)-alpha-D-GlcN2S3S6S in the T. phylippinarum heparin, in comparison with bovine
      mucosal heparin and a sample of porcine mucosal heparin previously published.
      Furthermore, as expected from the oligosaccharide compositional analysis, due to
      the presence of a great mol % (80.6%) of the trisulfated disaccharide DeltaUA2S(1
      ->4)-alpha-D-GlcN2S6S, mollusc heparin is a more sulfated polysaccharide than
      bovine mucosal heparin (73.5%) and a sample of porcine mucosal (72.8%) heparin
      previously reported. To our knowledge, this is the first article describing a
      clam heparin having the ATIII binding site mainly identical to that of human and
      porcine intestinal mucosal heparins and bovine intestinal mucosal heparin but
      different from that found in beef lung heparin.

PMID- 15253930
TI  - Production of N-sulfated polysaccharides using yeast-expressed N-deacetylase/N
      sulfotransferase-1 (NDST-1).
AB  - Heparan sulfate/heparin N-deacetylase/N-sulfotransferase-1 (NDST-1) is a critical
      enzyme involved in heparan sulfate/heparin biosynthesis. This dual-function
      enzyme modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N
      sulfated heparosan. N-sulfation is an absolute requirement for the subsequent
      epimerization and O-sulfation steps in heparan sulfate/heparin biosynthesis. We
      have expressed rat liver (r) NDST-1 in Saccharomyces cerevisiae as a soluble
      protein. The yeast-expressed enzyme has both N-deacetylase and N-sulfotransferase
      activities. N-acetyl heparosan, isolated from Escherichia coli K5 polysaccharide,
      de-N-sulfated heparin (DNSH) and completely desulfated N-acetylated heparan
      sulfate (CDSNAcHS) are all good substrates for the rNDST-1. However, N
      desulfated, N-acetylated heparin (NDSNAcH) is a poor substrate. The rNDST-1 was
      partially purified on heparin Sepharose CL-6B. Purified rNDST-1 requires Mn(2+)
      for its enzymatic activity, can utilize PAPS regenerated in vitro by the PAPS
      cycle (PAP plus para-nitrophenylsulfate in the presence of arylsulfotransferase
      IV), and with the addition of exogenous PAPS is capable of producing 60-65% N
      sulfated heparosan from E. coli K5 polysaccharide or Pasteurella multocida
      polysaccharide.

PMID- 15253931
TI  - Immunolocalization and functional role of Sclerotium rolfsii lectin in
      development of fungus by interaction with its endogenous receptor.
AB  - Many fungi are known to secrete lectins, but their functional roles are not
      clearly understood. Sclerotium rolfsii, a soilborne plant pathogenic fungus
      capable of forming fruiting bodies called sclerotial bodies, secrete a cell wall
      associated Thomsen-Friedenreich antigen-specific lectin. To understand the
      functional role of this lectin, we examined its occurrence and expression during
      development of the fungus. Furthermore, putative endogenous receptors of the
      lectin were examined to substantiate the functional role of the lectin.
      Immunolocalization studies using FITC-labeled lectin antibodies revealed discrete
      distribution of lectin sites at the branching points of the developing mycelia
      and uniformly occurring lectin sites on the mature sclerotial bodies. During
      development of the fungus the lectin is expressed in small amounts on the
      vegetative mycelia and reaching very high levels in mature sclerotial bodies with
      a sudden spurt in secretion at the maturation stage. Capping of the lectin sites
      on the sclerotial bodies by lectin antibodies or haptens inhibit strongly the
      germination of these bodies, indicating functional significance of the lectin. At
      the maturation stage the lectin interacts with the cell wall-associated putative
      endogenous receptor leading to the aggregation of mycelium to form sclerotial
      bodies. The lectin-receptor complex probably acts as signaling molecule in the
      germination process of sclerotial bodies. Using biotinylated lectin, the
      receptors were identified by determining the specific lectin binding to lipid
      components, extracted from sclerotial bodies, and separated on thin-layer
      chromatograms. Preliminary characterization studies indicated that the receptors
      are glycosphingolipids and resemble inositolphosphoceramides. These findings
      together demonstrate the importance of lectin-receptor interactions to explain
      hitherto speculated functional role of the lectins and also the
      glycosphingolipids of fungi.

PMID- 15253932
TI  - Sonic hedgehog, secreted by amacrine cells, acts as a short-range signal to
      direct differentiation and lamination in the zebrafish retina.
AB  - Neurogenesis in the zebrafish retina occurs in several waves of differentiation.
      The first neurogenic wave generates ganglion cells and depends on hedgehog (hh)
      signaling activity. Using transgenic zebrafish embryos that express GFP under the
      control of the sonic hedgehog (shh) promoter, we imaged the differentiation wave
      in the retina and show that, in addition to the wave in the ganglion cell layer,
      shh expression also spreads in the inner nuclear layer. This second wave
      generates amacrine cells expressing shh, and although it overlaps temporally with
      the first wave, it does not depend on it, as it occurs in the absence of ganglion
      cells. We also show that differentiation of cell types found in the inner and
      outer nuclear layers, as well as lamination of the retina, depends on shh. By
      performing mosaic analysis, we demonstrate that Shh directs these events as a
      short-range signal within the neural retina.

PMID- 15253933
TI  - The TOR pathway interacts with the insulin signaling pathway to regulate C.
      elegans larval development, metabolism and life span.
AB  - The highly conserved target-of-rapamycin (TOR) protein kinases control cell
      growth in response to nutrients and growth factors. In mammals, TOR has been
      shown to interact with raptor to relay nutrient signals to downstream translation
      machinery. We report that in C. elegans, mutations in the genes encoding CeTOR
      and raptor result in dauer-like larval arrest, implying that CeTOR regulates
      dauer diapause. The daf-15 (raptor) and let-363 (CeTOR) mutants shift metabolism
      to accumulate fat, and raptor mutations extend adult life span. daf-15
      transcription is regulated by DAF-16, a FOXO transcription factor that is in turn
      regulated by daf-2 insulin/IGF signaling. This is a new mechanism that regulates
      the TOR pathway. Thus, DAF-2 insulin/IGF signaling and nutrient signaling
      converge on DAF-15 (raptor) to regulate C. elegans larval development, metabolism
      and life span.

PMID- 15253934
TI  - Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior
      heart field during mouse embryonic development.
AB  - The vertebrate heart forms initially as a linear tube derived from a primary
      heart field in the lateral mesoderm. Recent studies in mouse and chick have
      demonstrated that the outflow tract and right ventricle originate from a separate
      source of mesoderm that is anterior to the primary heart field. The discovery of
      this anterior, or secondary, heart field has led to a greater understanding of
      the morphogenetic events involved in heart formation; however, many of the
      underlying molecular events controlling these processes remain to be determined.
      The MADS domain transcription factor MEF2C is required for proper formation of
      the cardiac outflow tract and right ventricle, suggesting a key role in anterior
      heart field development. Therefore, as a first step toward identifying the
      transcriptional pathways upstream of MEF2C, we introduced a lacZ reporter gene
      into a bacterial artificial chromosome (BAC) encompassing the murine Mef2c locus
      and used this recombinant to generate transgenic mice. This BAC transgene was
      sufficient to recapitulate endogenous Mef2c expression, and comparative sequence
      analyses revealed multiple regions of significant conservation in the noncoding
      regions of the BAC. We show that one of these conserved noncoding regions
      represents a transcriptional enhancer that is sufficient to direct expression of
      lacZ exclusively to the anterior heart field throughout embryonic development.
      This conserved enhancer contains two consensus GATA binding sites that are
      efficiently bound by the zinc finger transcription factor GATA4 and are
      completely required for enhancer function in vivo. This enhancer also contains
      two perfect consensus sites for the LIM-homeodomain protein ISL1. We show that
      these elements are specifically bound by ISL1 and are essential for enhancer
      function in transgenic embryos. Thus, these findings establish Mef2c as the first
      direct transcriptional target of ISL1 in the anterior heart field and support a
      model in which GATA factors and ISL1 serve as the earliest transcriptional
      regulators controlling outflow tract and right ventricle development.

PMID- 15253935
TI  - Localized Notch signal acts through eyg and upd to promote global growth in
      Drosophila eye.
AB  - Notch (N) signal is activated at the dorsoventral (DV) border of the Drosophila
      eye disc and is important for growth of the eye disc. In this study, we showed
      that the Pax protein Eyg is a major effector mediating the growth promotion
      function of N. eyg transcription is induced by N signaling occurring at the DV
      border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be
      compensated by overexpressing eyg, whereas loss of the downstream eyg blocked the
      function of N signaling. In addition, we showed that N and eyg could induce
      expression of upd, which encodes the ligand for the Jak/STAT pathway and acts
      over long distance to promote cell proliferation. Loss of eyg or N can be
      compensated by overexpressing upd. These results suggest that upd is a major
      effector mediating the function of eyg and N. The functional link from N to eyg
      to upd explains how the localized Notch activation can achieve global growth
      control.

PMID- 15253936
TI  - Coordinated regulation of gene expression by Brn3a in developing sensory ganglia.
AB  - Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in
      sensory axon growth and abnormal sensory apoptosis. We have determined the
      regulatory targets of Brn3a in the developing trigeminal ganglion using
      microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates
      the coordinated expression of neurotransmitter systems, ion channels, structural
      components of axons and inter- and intracellular signaling systems. Loss of Brn3a
      also results in the ectopic expression of transcription factors normally detected
      in earlier developmental stages and in other areas of the nervous system. Target
      gene expression is normal in heterozygous mice, consistent with prior work
      showing that autoregulation by Brn3a results in gene dosage compensation.
      Detailed examination of the expression of several of these downstream genes
      reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to
      be conserved in more posterior sensory ganglia but not in the CNS neurons that
      express this factor.

PMID- 15253937
TI  - The establishment of axial patterning in the maize leaf.
AB  - The maize leaf consists of four distinct tissues along its proximodistal axis:
      sheath, ligule, auricle and blade. liguleless1 (lg1) functions cell autonomously
      to specify ligule and auricle, and may propagate a signal that correctly
      positions the blade-sheath boundary. The dominant Wavy auricle in blade (Wab1)
      mutation disrupts both the mediolateral and proximodistal axes of the maize leaf.
      Wab1 leaf blades are narrow and ectopic auricle and sheath extend into the blade.
      The recessive lg1-R mutation exacerbates the Wab1 phenotype; in the double
      mutants, most of the proximal blade is deleted and sheath tissue extends along
      the residual blade. We show that lg1 is misexpressed in Wab1 leaves. Our results
      suggest that the Wab1 defect is partially compensated for by lg1 expression. A
      mosaic analysis of Wab1 was conducted in Lg1+ and lg1-R backgrounds to determine
      if Wab1 affects leaf development in a cell-autonomous manner. Normal tissue
      identity was restored in all wab1+/- sectors in a lg1-R mutant background, and in
      three quarters of sectors in a Lg1+ background. These results suggest that lg1
      can influence the autonomy of Wab1. In both genotypes, leaf-halves with wab1+/-
      sectors were significantly wider than non-sectored leaf-halves, suggesting that
      Wab1 acts cell-autonomously to affect lateral growth. The mosaic analysis, lg1
      expression data and comparison of mutant leaf shapes reveal previously unreported
      functions of lg1 in both normal leaf development and in the dominant Wab1 mutant.

PMID- 15253938
TI  - Conditional beta1-integrin gene deletion in neural crest cells causes severe
      developmental alterations of the peripheral nervous system.
AB  - Integrins are transmembrane receptors that are known to interact with the
      extracellular matrix and to be required for migration, proliferation,
      differentiation and apoptosis. We have generated mice with a neural crest cell
      specific deletion of the beta1-integrin gene to analyse the role of beta1
      integrins in neural crest cell migration and differentiation. This targeted
      mutation caused death within a month of birth. The loss of beta1-integrins from
      the embryo delayed the migration of Schwann cells along axons and induced
      multiple defects in spinal nerve arborisation and morphology. There was an almost
      complete absence of Schwann cells and sensory axon segregation and defective
      maturation in neuromuscular synaptogenesis. Thus, beta1-integrins are important
      for the control of embryonic and postnatal peripheral nervous system development.

PMID- 15253939
TI  - FGF acts directly on the somitic tendon progenitors through the Ets transcription
      factors Pea3 and Erm to regulate scleraxis expression.
AB  - During somite development, a fibroblast growth factor (FGF) signal secreted from
      the myotome induces formation of a scleraxis (Scx)-expressing tendon progenitor
      population in the sclerotome, at the juncture between the future lineages of
      muscle and cartilage. While overexpression studies show that the entire
      sclerotome is competent to express Scx in response to FGF signaling, the normal
      Scx expression domain includes only the anterior and posterior dorsal sclerotome.
      To understand the molecular basis for this restriction, we examined the
      expression of a set of genes involved in FGF signaling and found that several
      members of the Fgf8 synexpression group are co-expressed with Scx in the dorsal
      sclerotome. Of particular interest were the Ets transcription factors Pea3 and
      Erm, which function as transcriptional effectors of FGF signaling. We show here
      that transcriptional activation by Pea3 and Erm in response to FGF signaling is
      both necessary and sufficient for Scx expression in the somite, and propose that
      the domain of the somitic tendon progenitors is regulated both by the restricted
      expression of Pea3 and Erm, and by the precise spatial relationship between these
      Ets transcription factors and the FGF signal originating in the myotome.

PMID- 15253940
TI  - Functional divergence between eyeless and twin of eyeless in Drosophila
      melanogaster.
AB  - Pax6 genes encode transcription factors with two DNA-binding domains that are
      highly conserved during evolution. In Drosophila, two Pax6 genes function in a
      pathway in which twin of eyeless (toy) directly regulates eyeless (ey), which is
      necessary for initiating the eye developmental pathway. To investigate the gene
      duplication of Pax6 that occurred in holometabolous insects like Drosophila and
      silkworm, we used different truncated forms of toy and small eyes (sey), and
      tested their capacity to induce ectopic eye development in an ey-independent
      manner. Even though the Paired domains of TOY and SEY have DNA-binding properties
      that differ from those of the Paired domain of EY, they all are capable of
      inducing ectopic eye development in an ey mutant background. We also show that
      one of the main functional differences between toy and ey lies in the C-terminal
      region of their protein products, implying differences in their transactivation
      potential. Furthermore, we show that only the homeodomain (HD) of EY is able to
      downregulate the expression of Distal-less (Dll), a feature that is required
      during endogenous eye development. These results suggest distinct functions of
      the two DNA-binding domains of TOY and EY, and significant evolutionary
      divergence between the two Drosophila Pax6 genes.

PMID- 15253941
TI  - Will oral antithrombin agents replace warfarin?
AB  - The new oral direct thrombin inhibitor ximelagatran is at least equivalent to
      warfarin for stroke prevention in patients with non-valvar atrial fibrillation,
      and seems to be a promising adjunct to aspirin after acute coronary syndrome

PMID- 15253942
TI  - Glucocorticoid treatment and cardiovascular disease.
AB  - The propensity of glucocorticoids to produce hyperglycaemia, hypertension,
      dyslipidaemia, and central obesity has long been a cause for concern among
      physicians regarding possible adverse cardiovascular events. Should heart failure
      be added to this list of concerns?

PMID- 15253943
TI  - Jesting Pilate, genetic case-control association studies, and Heart.
AB  - "What is truth said jesting Pilate...." On truth, F Bacon 1561-1626

PMID- 15253945
TI  - Complete regression of pulmonary vein aneurysm caused by mitral regurgitation.

PMID- 15253946
TI  - Multiple pathogenetic mechanisms in X linked dilated cardiomyopathy.
AB  - X linked dilated cardiomyopathy is a familial disease that is allelic to Duchenne
      and Becker muscular dystrophies and caused by mutations in the dystrophin gene.
      In several families with X linked dilated cardiomyopathy, the pattern of
      expression of dystrophin mutations in cardiac muscle differs from that in
      skeletal muscle. A number of these mutations affect transcription and splicing of
      the dystrophin gene in a tissue specific manner; others may affect regions of
      dystrophin that are presumed to have a more important role in cardiac than in
      skeletal muscle. These mutations are important because they highlight the
      fundamental differences in processing of the dystrophin gene between skeletal and
      cardiac tissues, as well as differences in the functional domains more relevant
      for one tissue or the other. This review focuses on the major mechanisms that
      have been proposed to explain this disorder.

PMID- 15253947
TI  - Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease
      caused by mutations in sarcomeric genes. However, extensive genetic screening
      failed to identify a mutation in about a third of cases. One possible explanation
      is that other diseases, caused by other genes, may mimic HCM. OBJECTIVE: To
      investigate the possible involvement of Danon's disease, an X linked lysosomal
      disease, in a large population of patients with HCM. METHODS: A population of 197
      index cases was considered; 124 were subsequently excluded because of a mutation
      in sarcomeric genes and 23 because of autosomal dominant inheritance. Fifty index
      cases were therefore included in molecular analysis (direct sequencing) of the
      lysosome associated membrane protein 2 (LAMP2) gene responsible for Danon's
      disease. RESULTS: Two new mutations leading to premature stop codons were
      identified in patients who evolved towards severe heart failure (< 25 years old):
      657C>T and 173_179del. The prevalence was therefore 1% of the total population
      (two of 197) or 4% of enrolled index cases (two of 50). Interestingly, Danon's
      disease was responsible for half of the cases (two of four) with HCM and clinical
      skeletal myopathy but was not involved in isolated HCM (none of 41). CONCLUSIONS:
      Danon's disease may be involved in patients with previously diagnosed as HCM. A
      diagnosis strategy is proposed. To distinguish HCM from Danon's disease is
      important because the clinical evolution, prognosis, mode of inheritance, and
      therefore genetic counselling are very different.

PMID- 15253948
TI  - Calcified mediastinal haematoma: a rare case of cardiac constriction.

PMID- 15253950
TI  - Impending septal rupture in myocardial infarction detected by cardiac magnetic
      resonance imaging.

PMID- 15253949
TI  - Markers of inflammation and multiple complex stenoses (pancoronary plaque
      vulnerability) in patients with non-ST segment elevation acute coronary
      syndromes.
AB  - OBJECTIVE: To assess the relation between markers of inflammation and the
      presence of multiple vulnerable plaques in patients with non-ST segment elevation
      acute coronary syndromes. DESIGN: Prospective cohort study of 55 patients with
      non-ST segment elevation acute coronary syndromes and angiographically documented
      coronary disease. Blood samples were obtained at study entry for the assessment
      of high sensitivity C reactive protein (CRP), neopterin, and neutrophil count.
      Coronary stenoses were assessed by quantitative computerised angiography and
      classified as "complex" (irregular borders, ulceration, or filling defects) or
      "smooth" (absence of complex features). Extent of disease was also assessed by a
      validated angiographic score. RESULTS: Neutrophil count (r = 0.36, p = 0.007),
      CRP concentration (r = 0.33, p = 0.02), and neopterin concentration (r = 0.45, p
      < 0.001) correlated with the number of complex stenoses. Patients with multiple
      (three or more) complex stenoses, but not patients with multiple smooth lesions,
      had a higher neutrophil count (5.9 (1.4) x 10(9)/l v 4.8 (1.4) x 10(9)/l, p =
      0.02), CRP concentration (log transformed) (1.08 (0.63) v 0.6 (0.6), p = 0.03),
      and neopterin concentration (log transformed) (0.94 (0.18) v 0.79 (0.15), p =
      0.002). Multiple regression analysis showed that neopterin concentration (B =
      4.8, 95% confidence interval (CI) 1.9 to 7.7, p = 0.002) and extent of coronary
      artery disease (B = 0.6, 95% CI 0.03 to 1.2, p = 0.04) were independently
      associated with the number of complex stenoses. CONCLUSIONS: Acute inflammatory
      markers such as high neutrophil count, CRP concentration, and neopterin
      concentration correlate with the presence of multiple angiographically complex
      coronary stenoses. Neopterin concentration was a stronger predictor of multiple
      complex plaques than were neutrophil count and CRP concentration. These findings
      suggest that a relation exists between inflammation and pancoronary plaque
      vulnerability.

PMID- 15253952
TI  - Unstable angina in a patient with single coronary artery.

PMID- 15253951
TI  - Monocyte proinflammatory cytokine release is higher and glucocorticoid
      sensitivity is lower in middle aged men than in women independent of
      cardiovascular risk factors.
AB  - OBJECTIVE: To investigate whether stimulated monocyte cytokine release and its
      inhibition by glucocorticoids differs between men and women. DESIGN: In vitro
      monocyte interleukin 6 (IL-6) and tumour necrosis factor alpha (TNFalpha) release
      after lipopolysaccharide stimulation were assessed with and without co-incubation
      with increasing doses of dexamethasone and hydrocortisone separately.
      Glucocorticoid sensitivity was defined as the amount of a particular
      glucocorticoid required to inhibit lipopolysaccharide stimulated monocyte
      cytokine release by 50%. The established cardiovascular risk factors of age, body
      mass index, number of cigarettes smoked daily, low density cholesterol to high
      density cholesterol ratio, systolic and diastolic blood pressure, and haemoglobin
      A1c were used as covariates. SETTING: Aircraft manufacturing plant in southern
      Germany. PATIENTS: 269 middle aged male and 36 middle aged female employees.
      RESULTS: Release of monocyte IL-6 and TNFalpha (each p = 0.001) was higher in
      samples from men than in those from women. Inhibition of lipopolysaccharide
      stimulated IL-6 and TNFalpha release by either glucocorticoid was less pronounced
      in samples from men than in those from women (IL-6: dexamethasone p = 0.033,
      hydrocortisone p = 0.029; TNFalpha: dexamethasone p < 0.001, hydrocortisone p =
      0.089). CONCLUSIONS: The finding suggests that proinflammatory activity of
      circulating monocytes is higher in men than in women independent of
      cardiovascular risk factors, thereby providing one explanation for the relatively
      greater coronary risk in men.

PMID- 15253954
TI  - Septic emboli from aortic valve endocarditis.

PMID- 15253953
TI  - Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular
      disease in a population based case-control study.
AB  - OBJECTIVE: To assess whether use of oral glucocorticoids is associated with
      cardiovascular and cerebrovascular morbidity. DESIGN AND SETTING: Nested case
      control study within a cohort of patients (> or = 50 years old) with at least one
      prescription for oral or non-systemic glucocorticoids. Data were from the general
      practice research database. PATIENTS: 50 656 patients were identified with a
      first record for ischaemic heart disease (International classification of
      diseases, ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke
      or transient ischaemic attack (ICD-9 codes 430-436), or heart failure (ICD-9 code
      428) between 1988 and 1998. One control was matched to each case by sex, age,
      general practice, underlying disease, and calendar time. MAIN OUTCOME MEASURE:
      Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using
      oral glucocorticoids compared with non-users. RESULTS: There was a significant
      association between ever use of oral glucocorticoids and any cardiovascular or
      cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to
      1.29). The association was stronger for current use of oral glucocorticoids than
      for recent or past use. Among current users, the highest ORs were observed in the
      group with the highest average daily dose, although the dose-response relation
      was not continuous. Current use was associated with an increased risk of heart
      failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between
      patients with rheumatoid arthritis, patients with chronic obstructive pulmonary
      disease, and patients without either of the two conditions. Also, current use was
      associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95%
      CI 1.11 to 1.29). CONCLUSIONS: Oral glucocorticoid use was identified as a risk
      factor for heart failure. However, the evidence remains observational and only a
      randomised controlled trial of glucocorticoid treatment versus other disease
      modifying agents is likely to distinguish the importance of the underlying
      disease activity from its treatment in predicting cardiovascular outcomes.

PMID- 15253955
TI  - Reliability of N-terminal proBNP assay in diagnosis of left ventricular systolic
      dysfunction within representative and high risk populations.
AB  - OBJECTIVE: To determine the performance of a new NT-proBNP assay in comparison
      with brain natriuretic peptide (BNP) in identifying left ventricular systolic
      dysfunction (LVSD) in randomly selected community populations. METHODS: Blood
      samples were taken prospectively in the community from 591 randomly sampled
      individuals over the age of 45 years, stratified for age and socioeconomic status
      and divided into four cohorts (general population; clinically diagnosed heart
      failure; patients on diuretics; and patients deemed at high risk of heart
      failure). Definite heart failure (left ventricular ejection fraction (LVEF) <
      40%) was identified in 33 people. Samples were handled as though in routine
      clinical practice. The laboratories undertaking the assays were blinded. RESULTS:
      Using NT-proBNP to diagnose LVEF < 40% in the general population, a level of > 40
      pmol/l had 80% sensitivity, 73% specificity, 5% positive predictive value (PPV),
      100% negative predictive value (NPV), and an area under the receiver-operator
      characteristic curve (AUC) of 76% (95% confidence interval (CI) 46% to 100%). For
      BNP to diagnose LVSD, a cut off level of > 33 pmol/l had 80% sensitivity, 88%
      specificity, 10% PPV, 100% NPV, and AUC of 88% (95% CI 75% to 100%). Similar NPVs
      were found for patients randomly screened from the three other populations.
      CONCLUSIONS: Both NT-proBNP and BNP have value in diagnosing LVSD in a community
      setting, with similar sensitivities and specificities. Using a high cut off for
      positivity will confirm the diagnosis of LVSD but will miss cases. At lower cut
      off values, positive results will require cardiac imaging to confirm LVSD.

PMID- 15253956
TI  - Testosterone replacement in hypogonadal men with angina improves ischaemic
      threshold and quality of life.
AB  - BACKGROUND: Low serum testosterone is associated with several cardiovascular risk
      factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin
      resistance. Testosterone has been reported to improve symptoms of angina and
      delay time to ischaemic threshold in unselected men with coronary disease.
      OBJECTIVE: This randomised single blind placebo controlled crossover study
      compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men
      with ischaemic heart disease and hypogonadism. RESULTS: Baseline total
      testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and
      1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between
      testosterone and placebo phase showed that mean (SD) trough testosterone
      concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone)
      (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to
      1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing
      increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated
      questionnaires all improved. Compared with placebo, testosterone therapy was also
      associated with a significant reduction of total cholesterol and serum tumour
      necrosis factor alpha with delta values of -0.41 (0.54) mmol/l (p = 0.04) and 
      1.8 (2.4) pg/ml (p = 0.05) respectively. CONCLUSION: Testosterone replacement
      therapy in hypogonadal men delays time to ischaemia, improves mood, and is
      associated with potentially beneficial reductions of total cholesterol and serum
      tumour necrosis factor alpha.

PMID- 15253957
TI  - Rapid access arrhythmia clinic for the diagnosis and management of new
      arrhythmias presenting in the community: a prospective, descriptive study.
AB  - OBJECTIVE: To investigate whether a rapid access approach is useful for the
      evaluation of patients with symptoms suggestive of a new cardiac arrhythmia.
      DESIGN: Prospective, descriptive study. SETTING: Secondary care based rapid
      access arrhythmia clinic in West London, UK. PARTICIPANTS: Patients referred by
      their general practitioner or the emergency department with symptoms suggestive
      of a new cardiac arrhythmia. MAIN OUTCOME MEASURES: Number of patients with a
      newly diagnosed significant arrhythmia. Number of patients with diagnosed atrial
      fibrillation. Number of eligible, moderate, and high risk patients treated with
      warfarin. RESULTS: Over a 25 month period 984 referrals were assessed. The mean
      age was 55 years (range 20-90 years) and 56% were women. The median time from
      referral to assessment was one day. A significant cardiac arrhythmia was newly
      diagnosed in 40% of patients referred to the RAAC. The most common arrhythmia was
      atrial fibrillation, with 203 new cases (21%). Of these, 74% of eligible patients
      over 65 were treated with warfarin. Other arrhythmias diagnosed were
      supraventricular tachycardias (127 (13%)), conduction disorders (43 (4%)), and
      non-sustained ventricular tachycardia (21 (2%)). Vasovagal syncope was diagnosed
      for 53 patients (5%). The most frequent diagnosis was symptomatic ventricular and
      supraventricular extrasystoles (355 (36%)). CONCLUSION: A rapid access arrhythmia
      clinic is an innovative approach to the diagnosis and management of new cardiac
      arrhythmias in the community. It provides a rapid diagnosis, stratifies risk, and
      leads to prompt initiation of effective treatment for this population.

PMID- 15253958
TI  - Cardiac tumour in a neonate with left ventricular outflow tract obstruction.

PMID- 15253960
TI  - Electrocardiographic gated multislice computed tomography of Uhl's anomaly.

PMID- 15253959
TI  - Local symptoms at the site of pacemaker implantation indicate latent systemic
      infection.
AB  - BACKGROUND: To determine whether local complications at the site of pacemaker
      implantation indicate infection of the intravascular part of the lead as well as
      of the pacemaker pocket. METHODS: 105 patients admitted for local inflammatory
      findings, impending pacemaker or lead exteriorisation, frank pacemaker or lead
      exteriorisation, or overt infection were studied prospectively. After systematic
      lead extraction, the initial clinical presentation was related to the results of
      lead cultures. RESULTS: Regardless of the initial presentation, the intravascular
      parts of the leads gave positive cultures in 79.3% of patients. Additionally,
      91.6% of the cultures of the extravascular lead segments were positive, in
      contrast to 38.1% positivity for wound swab cultures. No clinical observations or
      laboratory investigations permitted identification of patients with negative lead
      cultures. In a subgroup of 50 patients with manifestations strictly limited to
      the pacemaker implantation site, cultures of intravascular lead segments were
      positive in 72%. Infection recurred in 4/8 patients without complete lead body
      extraction (50%) v 1/97 patients (1.0%) whose leads were totally extracted (p <
      0.001). CONCLUSIONS: Local complications at the site of pacemaker implantation
      are usually associated with infection of the intravascular part of the leads,
      with a risk of progressing to systemic infection. Such local symptoms should
      prompt the extraction of leads even in the absence of other infectious
      manifestations.

PMID- 15253961
TI  - Relation between different methods for analysing ST segment deviation and infarct
      size as assessed by positron emission tomography.
AB  - OBJECTIVE: To study the relation between resolution of ST segment deviation and
      infarct size using positron emission tomography. METHODS: 45 patients with ST
      segment elevation acute myocardial infarction treated with thrombolysis or
      percutaneous coronary intervention were studied prospectively. An ECG was taken
      before and at (mean (SD)) 100 (45) min after reperfusion therapy. ECGs were
      analysed by three methods. Residual ST segment deviation, obtained from the ECG
      immediately after completion of reperfusion therapy, was defined by summation for
      each of the three methods. Relative resolution of ST segment deviation was
      defined as the absolute resolution divided by the ST segment deviation score at
      baseline x 100 (%). After 29 (14) hours, myocardial blood flow was measured with
      13NH3. For each patient, the regions with a myocardial blood flow < 80% of
      normally perfused myocardium ( = hypoperfusion) and < 50% ( = no reflow) were
      automatically delineated. RESULTS: Substantial differences were found between
      different ECG analysis methods. There were moderate correlations between the area
      with myocardial hypoperfusion and ST segment deviation scores at baseline and
      after reperfusion therapy. After reperfusion therapy, residual ST segment
      deviation in the single lead with maximum ST segment deviation was as good at
      discriminating between tertiles of myocardial damage as summed ST segment
      elevation. Relative ST segment resolution did not discriminate between different
      degrees of myocardial damage. CONCLUSIONS: In the individual patient, residual ST
      segment deviation after reperfusion in the single lead with maximum ST segment
      deviation is at least as good as summed ST elevation in predicting final
      myocardial damage.

PMID- 15253963
TI  - Sinus venosus type of atrial septal defect with partial anomalous pulmonary
      venous return evaluated by multislice CT.

PMID- 15253962
TI  - Evaluation of aortic stenosis by cardiovascular magnetic resonance imaging:
      comparison with established routine clinical techniques.
AB  - OBJECTIVE: To evaluate whether direct planimetry of aortic valve area (AVA) by
      cardiac magnetic resonance (CMR) imaging is a reliable tool for determining the
      severity of aortic stenosis compared with transthoracic echocardiography (TTE),
      transoesophageal echocardiography (TOE), and cardiac catheterisation. METHODS: 44
      symptomatic patients with severe aortic stenosis were studied. By cardiac
      catheterisation AVA was calculated by the Gorlin equation. AVA was measured with
      CMR from steady state free precession (true fast imaging with steady state
      precession) by planimetry. AVA was also determined from TOE images by planimetry
      and from TTE images by the continuity equation. RESULTS: Bland-Altman analysis
      evaluating intraobserver and interobserver variability showed a very small bias
      for both (-0.016 and 0.019, respectively; n = 20). Bias and limits of agreement
      between CMR and TTE were 0.05 (-0.35, 0.44) cm2 (n = 37), between CMR and TOE
      0.02 (-0.39, 0.42) cm2 (n = 32), and between CMR and cardiac catheterisation 0.09
      (-0.30, 0.47) cm2 (n = 36). The sensitivity and specificity of CMR to detect AVA
      < or = 0.80 cm2 measured by cardiac catheterisation was 78% and 89%, of TOE 70%
      and 70%, and of TTE 74% and 67%, respectively. CONCLUSION: CMR planimetry is
      highly reliable and reproducible. Further, CMR planimetry had the best
      sensitivity and specificity of all non-invasive methods for detecting severe
      aortic stenosis in comparison with cardiac catheterisation. Therefore, CMR
      planimetry of AVA with steady state free precession is a new powerful diagnostic
      tool, particularly for patients with uncertain or discrepant findings by other
      modalities.

PMID- 15253964
TI  - Renal function and long term mortality after unstable angina/non-ST segment
      elevation myocardial infarction treated very early and predominantly with
      percutaneous coronary intervention.
AB  - OBJECTIVES: To quantify the impact of baseline renal function on in-hospital and
      long term mortality in patients with unstable angina/non-ST elevation acute
      myocardial infarction (UA/NSTEMI) treated with a very early invasive strategy.
      DESIGN: Prospective cohort study of 1400 consecutive patients with UA/NSTEMI
      undergoing coronary angiography and subsequent coronary stenting of the culprit
      lesion as the primary revascularisation strategy within 24 hours of admission.
      Patients were stratified according to calculated glomerular filtration rate (GFR)
      on admission. RESULTS: In-hospital mortality was 0% among patients with a GFR >
      or = 130 ml/min/1.73 m2, 0.4% with a GFR of 90-129 ml/min/1.73 m2, 2.6% with a
      GFR of 60-89 ml/min/1.73m2, and 5.1% with a GFR of < 60 ml/min/1.73 m2.
      Cumulative three year survival rates were 92.6%, 95.5%, 91.9%, and 76.8%,
      respectively. Patients with a GFR of < 60 ml/min/1.73 m2 were four times more
      likely to die in hospital (hazard ratio (HR) 4.0, 95% confidence interval (CI)
      1.8 to 9.1; p = 0.001) and four times more likely to die during long term follow
      up (HR 4.0, 95% CI 2.5 to 6.4; p < 0.001). After adjusting for potential
      confounders, a GFR of < 60 ml/min/1.73 m2 remained a strong independent predictor
      of long term mortality (HR 2.6, 95% CI 1.5 to 4.5; p = 0.001). CONCLUSIONS:
      Baseline renal function is a strong independent predictor of in-hospital and long
      term mortality after UA/NSTEMI treated with very early revascularisation.

PMID- 15253965
TI  - Free floating thrombus in left atrium.

PMID- 15253967
TI  - Saccular dilatations originating from the conus artery.

PMID- 15253968
TI  - Poor sensitivity of routine fetal anomaly ultrasound screening for antenatal
      detection of atrioventricular septal defect.
AB  - OBJECTIVE: To report the antenatal detection rate in a consecutive series of
      liveborn infants with atrioventricular septal defect (AVSD). DESIGN: Review and
      analysis of referrals for detailed fetal echocardiography and postnatal diagnosis
      of AVSD. SETTING: Tertiary referral centre for congenital heart disease centre
      with data prospectively collected between 1996 to 2001. RESULTS: 92 consecutively
      liveborn infants with AVSDs were identified of which 27 (29%) were detected by
      routine obstetric antenatal ultrasound. The antenatal diagnosis rate was worse
      for liveborn infants with trisomy 21 (12 of 49 (25%) v 15 of 43 (35%)
      chromosomally normal children) and for infants with AVSD without other structural
      heart disease (18 of 74 (24%) v 9 of 18 (50%) infants with associated structural
      heart disease). CONCLUSION: Despite the potential ability of fetal ultrasound to
      detect AVSDs, the antenatal diagnosis rate is poor. This is particularly true for
      infants with trisomy 21 and is of importance when counselling parents with an
      apparently normal fetal ultrasound scan.

PMID- 15253966
TI  - Echocardiographic predictors of adverse clinical events in children with dilated
      cardiomyopathy: a prospective clinical study.
AB  - OBJECTIVES: To compare tissue Doppler (TD) velocities between patients with
      dilated cardiomyopathy (DCM) and normal controls and to determine whether TD
      velocities, Tei index, right ventricular fractional area change, and left
      ventricular ejection fraction (LVEF) predict adverse clinical outcomes in
      children with DCM. METHODS: Prospective evaluation of children with DCM. RESULTS:
      54 children with DCM and 54 age and sex matched control group participants were
      studied. Mitral inflow velocities were similar for both groups except for
      decreased mitral deceleration time in patients with DCM. Systolic and diastolic
      TD velocities at the mitral annulus (septal and lateral sides) and tricuspid
      annulus were significantly reduced in children with DCM compared with controls (p
      < 0.001 for each). By multivariate analysis, after adjustment for Tei index and
      right ventricular fractional area change, decreased LVEF and tricuspid velocity
      during early diastole (Ea) were predictors of the primary end point (PEP), a
      composite end point consisting of need for hospitalisation or the outcome
      transplantation or death. Tricuspid Ea velocity < 8.5 cm/s had 87% specificity
      and 60% sensitivity for reaching the PEP. LVEF < 30% had 68% specificity and 74%
      sensitivity for the PEP. Combined LVEF < 30% and tricuspid Ea < 11.5 cm/s had
      100% specificity and 44% sensitivity for the PEP. CONCLUSIONS: Children with DCM
      have significantly lower TD velocities than normal controls. In such cases, lower
      LVEF (< 30%) is more sensitive but less specific than lower tricuspid Ea
      velocities (< 8.5 cm/s) in predicting which patients are at risk of
      hospitalisation, transplantation, or death.

PMID- 15253969
TI  - Persistent pulmonary hypertension late after neonatal aortic valvotomy: a
      consequence of an expanded surgical cohort.
AB  - BACKGROUND: Survival of neonates with critical aortic stenosis has improved over
      the past decade. Models based on morphological characteristics have been designed
      to help determine whether early survival is more likely after biventricular
      repair (surgical or balloon aortic valvotomy) or after a single ventricle staged
      palliative surgical strategy. However, late follow up data are lacking.
      OBJECTIVE: To report follow up data on survivors of neonatal aortic valvotomy who
      had persistent pulmonary hypertension caused by restriction to left ventricular
      filling. RESULTS: Of four medium term survivors of neonatal valvotomy for
      critical aortic stenosis who had persistent pulmonary hypertension, one died aged
      4 years and the other three have severe limitation of effort tolerance.
      CONCLUSIONS: This previously unreported late complication of "successful"
      biventricular repair for neonatal critical aortic stenosis is an important
      consideration in determining the initial management.

PMID- 15253970
TI  - Clinical impact of first and early second trimester fetal echocardiography on
      high risk pregnancies.
AB  - OBJECTIVE: To evaluate the clinical impact of fetal echocardiography before 16
      weeks' gestation on the management of pregnancies with fetuses at risk of
      congenital heart disease. DESIGN AND SETTING: Observational study in a fetal
      medicine unit. PARTICIPANTS AND METHODS: 222 consecutive women with high risk
      pregnancies (230 fetuses) underwent transabdominal fetal echocardiography at a
      median gestation of 14(+1) weeks. For 10%, transvaginal scans were also
      performed. Criteria for normal scans were normal sequential segmental analysis,
      symmetrical four chamber view, normal semilunar valves, arterial outflow tracts,
      and ductal and aortic arches. Early scans were compared with mid-second trimester
      fetal echocardiography. Postmortem and postnatal data were added. Adverse
      pregnancy outcomes were diagnosis of a major cardiac or extracardiac abnormality,
      chromosomal defects, intrauterine death, or termination of pregnancy. RESULTS:
      There were 21 abnormal cardiac scans (9%): 14 major structural defects (eight
      isolated, six with chromosomal or extracardiac abnormalities) in pregnancies
      resulting in three live births, one intrauterine death, and 10 terminated
      pregnancies. Seven scans showed asymmetry between right and left sided structures
      (two isolated, five with chromosomal or extracardiac abnormalities); six of the
      seven pregnancies were terminated. The scans were normal in 199 cases (87%).
      Cardiac follow up of 184 of 199 babies (93%) confirmed situs and connections. One
      case each of pulmonary stenosis and ventricular septal defect requiring postnatal
      intervention were diagnosed at later scans. In 28 of 199 (14%) babies there was a
      non-cardiac adverse outcome. First examination was not diagnostic for 10 (4%).
      CONCLUSION: Early fetal echocardiography in high risk pregnancies was diagnostic
      in 96%. Abnormal cardiac scans (isolated in 48%, major structural defects in 67%)
      led to termination of pregnancy in 76%. Most cardiac scans were normal, allowing
      family reassurance. The high number of adverse outcomes with normal cardiac
      anatomy stresses the need for a multidisciplinary approach to early fetal
      echocardiography.

PMID- 15253971
TI  - Optimal management of left ventricular aneurysms after ventricular septal defect
      closure.

PMID- 15253972
TI  - Dynamic changes of gene expression profiles during postnatal development of the
      heart in mice.
AB  - OBJECTIVE: To study postnatal cardiac differentiation in the mouse. HYPOTHESIS:
      There might be mechanisms or factors in cardiac differentiation that could be
      identified by systematic gene expression analysis during postnatal cardiac
      development. METHODS: Expression of 6144 genes was examined in mouse heart, from
      the newborn period (day 0), through day 7 and day 14 day, to adulthood, using the
      cDNA microarray approach. Northern blotting and immunohistochemical techniques
      were used to confirm the microarray results. RESULTS: Various cardiac development
      related genes involving the cell cycle (cyclin B1, proliferating cell nuclear
      antigen (PCNA), and Ki67), growth factors (IGF-II, pleiotrophin (PTN), and
      midkine (MK)), and transcriptional regulation, cytoskeleton, and detoxification
      enzymes were identified by microarray analysis. Some of these genes were also
      confirmed by Northern blotting and immunohistochemistry of their RNA and protein
      content. In vivo treatment with PTN (20 ng/g) increased bromodeoxyuridine
      incorporation (by 2.24-fold) and PCNA expression (by 1.71-fold) during day 7 to
      day 14, indicating that PTN induces cell proliferation in mouse heart.
      CONCLUSIONS: Global gene expression analysis in the whole heart may be useful in
      understanding the orchestrated process of postnatal development or terminal
      differentiation in the cardiac environment. These data are likely to be helpful
      in studying developmental anomalies of the heart in neonates.

PMID- 15253973
TI  - Emergency balloon mitral valvotomy for severe mitral stenosis during pregnancy.

PMID- 15253974
TI  - Central alpha2 adrenoceptors and the pathogenesis of carotid sinus
      hypersensitivity.

PMID- 15253975
TI  - Is there a sex bias in implantable cardioverter-defibrillator referral and
      prescription?

PMID- 15253977
TI  - Saccular aneurysm on the ascending aorta after cardiac surgery.

PMID- 15253976
TI  - Heterozygosity for the haemochromatosis mutation HFE C282Y is not a risk factor
      for angina.

PMID- 15253978
TI  - Metoprolol prophylaxis against postoperative atrial fibrillation increases length
      of hospital stay in patients not on pre-operative beta blockers: the beta blocker
      length of stay (BLOS) trial.

PMID- 15253979
TI  - Time course of transcardiac interleukin-6 release after coronary stenting for
      stable angina.

PMID- 15253980
TI  - Aneurysms of coronary artery with thrombus.

PMID- 15253981
TI  - Coronary collateral flow and peripheral blood monocyte concentration in patients
      treated with granulocyte-macrophage colony stimulating factor.

PMID- 15253982
TI  - Left main coronary artery occlusion in a patient with solitary coronary ostium in
      the right aortic sinus.

PMID- 15253983
TI  - Reliable detection of early myocardial dysfunction by tissue Doppler
      echocardiography in Becker muscular dystrophy.

PMID- 15253984
TI  - Management of dyslipidaemia.

PMID- 15253985
TI  - Interpretation of observational studies.

PMID- 15253986
TI  - Renal dysfunction and acceleration of coronary disease.

PMID- 15253988
TI  - Treatment of an ostial and a bifurcation lesion with a new directional
      atherectomy device.
AB  - Two cases of directional coronary atherectomy performed with a new 8 French
      monorail device for selective plaque excision are illustrated. This report
      underlines the technical characteristics of this new device, which allows the
      negotiation of complex coronary anatomy and emphasises the potential utility of
      directional coronary atherectomy in bifurcation and ostial lesions.

PMID- 15253987
TI  - Late incomplete lesion coverage following Cypher stent deployment for diffuse
      right coronary artery stenosis.
AB  - The availability of the only drug eluting stent currently approved in the USA has
      been limited, so that operators often resort to the deployment of multiple
      undersized stents and post-stenting high pressure inflations with larger balloons
      to achieve optimal lesion coverage and stent expansion. A case of stent fracture
      following percutaneous coronary intervention in which this strategy was used is
      reported.

PMID- 15253989
TI  - Constrictive pericarditis and pleuropulmonary fibrosis secondary to cabergoline
      treatment for Parkinson's disease.
AB  - A 63 year old man with a six year history of Parkinson's disease presented with
      signs of right heart failure following a knee replacement. Constrictive
      pericarditis was diagnosed and a radical pericardectomy performed. Six months
      later, the patient remained unwell with raised inflammatory markers. An
      inflammatory fibrotic reaction caused by cabergoline was diagnosed. He improved
      after cessation of cabergoline.

PMID- 15253990
TI  - Extensive primary cardiac liposarcoma with multiple functional complications.
AB  - Cardiac liposarcoma in a patient manifested multiple cardiac functional
      complications. Three dimensional reconstruction of the heart with multidetector
      row computed tomography made apparent each of the cardiac complications that
      resulted from the tumour's invasion. On the basis of these findings, the floating
      mass in the pulmonary artery and the compressing mass around the superior vena
      cava and interatrial septum were successfully resected. Pathological examination
      of the mass was consistent with well differentiated liposarcoma.

PMID- 15253991
TI  - Left ventricular haemangioma with papillary endothelial hyperplasia and liver
      involvement.
AB  - An intracardiac haemangioma with papillary endothelial hyperplasia (PEH) and
      liver involvement has not been previously reported in the English literature.
      This report describes a 65 year old man with a left ventricular haemangioma with
      PEH coexistent with multiple nodular hepatic haemangiomas. Transthoracic and
      transoesophageal echocardiography identified a large tumour in the left
      ventricular cavity with a pedicle connected to the apex. Abdominal sonography
      also identified multiple hyperechoic hepatic tumours. Magnetic resonance imaging
      showed hypervascularity of both the cardiac and hepatic lesions. The left
      ventricular tumour was totally resected and the liver nodules were biopsied.
      Tissue pathological study showed that both the left ventricular tumour and liver
      lesions were haemangiomas with PEH. The patient was discharged without
      complications postoperatively.

PMID- 15253992
TI  - Children's perceptions of their home and neighborhood environments, and their
      association with objectively measured physical activity: a qualitative and
      quantitative study.
AB  - Environmental factors may have an important influence on children's physical
      activity, yet children's perspectives of their home and neighborhood environments
      have not been widely assessed. The aim of this study was to investigate
      children's perceptions of their environments, and to examine associations between
      these perceptions and objectively measured physical activity. The sample
      consisted of 147, 10-year-old Australian children, who drew maps of their home
      and neighborhood environments. A subsample of children photographed places and
      things in these environments that were important to them. The maps were analyzed
      for themes, and for the frequency with which particular objects and locations
      appeared. Physical activity was objectively measured using accelerometers. Six
      themes emerged from the qualitative analysis of the maps and photographs: the
      family home; opportunities for physical activity and sedentary pursuits; food
      items and locations; green space and outside areas; the school and opportunities
      for social interaction. Of the 11 variables established from these themes, one
      home and two neighborhood factors were associated with children's physical
      activity. These findings contribute to a broader understanding of children's
      perceptions of their environment, and highlight the potential importance of the
      home and neighborhood environments for promoting physical activity behavior.

PMID- 15253993
TI  - Bullying: who does what, when and where? Involvement of children, teachers and
      parents in bullying behavior.
AB  - Bullying victimization is associated with several health issues. Prevention of
      bullying is therefore an important goal for health and education professionals.
      In the present study, 2766 children from 32 Dutch elementary schools participated
      by completing a questionnaire on bullying behavior, and the involvement of
      teachers, parents and classmates in bullying incidents. The results of this study
      show that bullying is still prevalent in Dutch schools. More than 16% of the
      children aged 9-11 years reported being bullied on a regular basis and 5.5%
      reported regular active bullying during the current school term. Almost half of
      the bullied children did not tell their teacher that they were being bullied.
      When teachers knew about the bullying, they often tried to stop it, but in many
      cases the bullying stayed the same or even got worse. With regard to active
      bullying, neither the majority of the teachers nor parents talked to the bullies
      about their behavior. Our results stress the importance of regular communication
      between children, parents, teachers and health care professionals with regard to
      bullying incidents. In addition, teachers need to learn effective ways to deal
      with bullying incidents. Schools need to adopt a whole-school approach with their
      anti-bullying interventions.

PMID- 15253994
TI  - 'Physical education makes you fit and healthy'. Physical education's contribution
      to young people's physical activity levels.
AB  - The purpose of this study was to assess physical activity levels during high
      school physical education lessons. The data were considered in relation to
      recommended levels of physical activity to ascertain whether or not physical
      education can be effective in helping young people meet health-related goals.
      Sixty-two boys and 60 girls (aged 11-14 years) wore heart rate telemeters during
      physical education lessons. Percentages of lesson time spent in moderate-and
      vigorous (MVPA) and vigorous intensity physical activity (VPA) were recorded for
      each student. Students engaged in MVPA and VPA for 34.3 +/- 21.8 and 8.3 +/-
      11.1% of lesson time, respectively. This equated to 17.5 +/- 12.9 (MVPA) and 3.9
      +/- 5.3 (VPA) min. Boys participated in MVPA for 39.4 +/- 19.1% of lesson time
      compared to the girls (29.1 +/- 23.4%; P < 0.01). High-ability students were more
      active than the average- and low-ability students. Students participated in most
      MVPA during team games (43.2 +/- 19.5%; P < 0.01), while the least MVPA was
      observed during movement activities (22.2 +/- 20.0%). Physical education may make
      a more significant contribution to young people's regular physical activity
      participation if lessons are planned and delivered with MVPA goals in mind.

PMID- 15253995
TI  - Covariates of current cigarette smoking among secondary school students in
      Budapest, Hungary, 1999.
AB  - To date, few studies have examined the relationship between health behavior risk
      factors and cigarette smoking in Hungary. From 1995 to 1999, the prevalence of
      current smoking increased from 35.9 to 46.0% among secondary students in
      Budapest, Hungary. The objective of the present study was to examine the
      association between smoking and other health behavior risk factors among
      secondary school students in Budapest. Surveys were administered during regular
      classes in 21 traditional and nine vocational/technical schools containing Grades
      9-12; 2410 students aged 15-18 years were included in the analysis. Overall,
      44.9% of males and 46.9% of females were current smokers. Smoking increased with
      age and was significantly higher among vocational/technical (60.2%) than
      traditional (43.1%) students. The likelihood of smoking was significantly higher
      among students who rarely or never used a seatbelt when riding in a car driven by
      someone else, currently used alcohol, had engaged in episodic heavy drinking, had
      had four or more sex partners during their lifetime or did not participate in
      vigorous physical activity. Health-risk behaviors are frequently interrelated.
      Findings suggest that programs designed to prevent smoking should consider
      related health-risk behaviors as part of a comprehensive program.

PMID- 15253996
TI  - Psychometric properties of virtual reality vignette performance measures: a novel
      approach for assessing adolescents' social competency skills.
AB  - This study examined the psychometric properties of performance measures for three
      novel, interactive virtual reality vignette exercises developed to assess social
      competency skills of at-risk adolescents. Performance data were collected from
      117 African-American male 15-17 year olds. Data for 18 performance measures were
      obtained, based on adolescents' interaction with a provocative virtual teenage
      character. Twelve of the 18 performance measures loaded on two factors
      corresponding to emotional control and interpersonal communication skills,
      providing support for their factorial validity. The internal reliability
      coefficients for the two multi-item measures were 0.88 and 0.91, respectively.
      Additional analyses with established measures of three psychosocial factors
      (beliefs supporting aggression, aggressive conflict-resolution style and
      hostility) and behavioral criteria (e.g., self-reported behavioral misconduct and
      drug use) provided limited support for the construct and criterion-related
      validity of the performance measures. Study findings suggest that the virtual
      reality vignette exercises may represent a promising approach for assessing
      adolescents' social competency skills.

PMID- 15253997
TI  - Building a health promotion agenda in local newspapers.
AB  - This is an analysis of newspaper coverage of breast cancer topics during a
      community-based health promotion campaign. The 4-year campaign, called the Breast
      Cancer Screening Campaign (BCSC), was devoted to promoting mammography screening
      in a Midwestern state. The BCSC included both paid advertising and volunteer-led
      community interventions that were intended, in part, to increase the flow of
      information about breast cancer and mammography screening in the local mass
      media. Findings showed that intervention was positively associated with local
      newspaper content about breast cancer, but the effects were confined to
      communities served by weekly newspapers. We discuss the implications of this
      study for future community-based health promotion campaigns.

PMID- 15253998
TI  - Why don't stage-based activity promotion interventions work?
AB  - Despite the well-described benefits of regular physical activity, around 70% of
      adults in the UK fail to meet current activity recommendations. Interventions
      based on the Transtheoretical, or Stages of Change, Model of behaviour change
      have been proposed as one potentially effective method of promoting physical
      activity levels. However, two recent reviews have found little evidence that
      individualized stage-based activity promotion interventions are any more
      effective than control conditions in promoting long-term adherence to increased
      levels of physical activity. Possible reasons for this are: that exercise
      behaviour is a more complex group of behaviours than currently recognized; that
      many algorithms for determining current stage of activity change have not been
      validated; that exercise behaviour is determined by a number of factors not
      addressed by stage-based interventions; that the stages of change model
      encourages focus on stage progression which is not always associated with
      behaviour change; and that truly stage-based interventions are highly complex
      requiring more than one level of development and evaluation--a challenge that has
      not yet been met. Thus, stage-based activity promotion interventions may simplify
      exercise behaviour beyond what is useful for practitioners and health promoters.
      Paradoxically, stage-based activity promotion interventions that have been
      developed to date may have failed to appreciate the true complexity of the task.

PMID- 15253999
TI  - Assessing medication adherence self-efficacy among low-literacy patients:
      development of a pictographic visual analogue scale.
AB  - Health behavior interventions are often grounded in Social Cognitive Theory, but
      instruments used to assess self-efficacy rely on verbal skills and yield scores
      that are highly positively skewed. Based on a review of the research literature
      and qualitative research with key informants, a pictographic medication adherence
      self-efficacy scale was developed. Two studies were conducted to test the
      pictographic and color visual analogue scale for assessing self-efficacy for
      medication adherence. Study 1 (N = 81) demonstrated that the pictographic self
      efficacy scale was internally consistent (alpha = 0.68), time stable (2-week test
      re-test r = 0.63), and showed evidence for convergent and divergent construct
      validity. Study 2 (N = 64) further supported the reliability of the pictographic
      self-efficacy scale with additional data supporting its convergent, divergent and
      criterion-related validity, including associations with medication adherence and
      HIV viral load. Distributions of self-efficacy scores approximated normal. This
      newly developed pictographic scale may be useful in assessing medication
      adherence self-efficacy in lower-literacy populations.

PMID- 15254000
TI  - Anti-smoking socialization beliefs among rural Native American and White parents
      of young children.
AB  - This study assesses similarities and differences in anti-smoking socialization
      beliefs of White and Native American parents in a low-income, rural population in
      northeastern Oklahoma. Data are from a population-based, cross-sectional
      children's environmental health study in which in-home interviews were conducted
      with 356 parents (56.2% White, 43.8% Native American), primarily mothers, of
      young children. Approximately 65% of the participants had a high school education
      or less and over 50% smoked. The Native American participants represented
      numerous tribes and did not live on reservations. Multivariate logistic
      regression models were used to examine associations between race/ethnicity,
      education, smoking status and six anti-smoking socialization beliefs. Results
      showed that White and Native American parents in this study were very similar in
      their anti-smoking socialization beliefs, with the one exception that Native
      American parents were less likely to believe that schools are better than parents
      in teaching children about the dangers of cigarette smoking. Parental education
      was significantly associated with the beliefs that all children will try smoking
      and that forbidding children to smoke will only make them want to smoke more,
      with less-educated parents more likely to share these beliefs. Findings suggest
      that interventions to promote anti-smoking socialization beliefs among parents
      with high school education or less may be important in low-income, rural
      communities with high smoking rates.

PMID- 15254001
TI  - Intervention to increase screening mammography among women 65 and older.
AB  - This paper reports the results of a practice-based intervention program to
      increase mammography screening among women 65 and older who receive their health
      care in the private sector. Forty-three primary-care practices and 2147 women in
      central and western North Carolina were enrolled in the study, and 1911 women
      completed all phases of the study. The intervention was a three-stage educational
      and counseling program designed to become progressively more intensive at each
      stage. The interventions included provider education in the form of current
      information on issues in mammography for older women, simply written educational
      materials on breast cancer and screening mailed to women, and a brief telephone
      counseling session for the women. While the analysis revealed no overall effect
      across all three stages of the intervention program, tests for interaction
      indicated a significant program effect for women who were 80 or older, had less
      than 9 years of education, were black, or had no private insurance to supplement
      Medicare. The results suggested that providing primary-care physicians with
      information on screening older women and providing the women with useful
      educational materials can increase participation in screening mammography among
      subgroups of women currently least likely to receive mammography screening.

PMID- 15254004
TI  - Assessment of prognosis in chronic coronary artery disease.

PMID- 15254003
TI  - Diagnosis of coronary artery disease by radionuclide myocardial perfusion
      imaging.

PMID- 15254005
TI  - Radionuclide imaging in risk assessment after acute coronary syndromes.

PMID- 15254006
TI  - Radionuclide techniques for the assessment of myocardial viability and
      hibernation.

PMID- 15254007
TI  - Myocardial perfusion scintigraphy and cost effectiveness of diagnosis and
      management of coronary heart disease.

PMID- 15254008
TI  - Nuclear cardiology in the UK: do we apply evidence based medicine?

PMID- 15254009
TI  - Selected food intake and risk of endometriosis.
AB  - BACKGROUND: To offer data on the relationship between diet and risk of pelvic
      endometriosis, we analysed data collected in the framework of two case-control
      studies. METHODS: Data from two case-control studies conducted in Northern Italy
      between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median
      age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of
      endometriosis, admitted to a network of obstetrics and gynaecology departments in
      Milan, Brescia and Pavia. Controls were 504 women (median age 34 years, range 20
      61) admitted for acute non-gynaecological, non-hormonal, non-neoplastic
      conditions. RESULTS: Compared to women in the lowest tertile of intake, a
      significant reduction in risk emerged for higher intake of green vegetables [odds
      ratio (OR) = 0.3 for the highest tertile of intake] and fresh fruit (OR = 0.6),
      whereas an increase in risk was associated with high intake of beef and other red
      meat (OR = 2.0) and ham (OR = 1.8). Consumption of milk, liver, carrots, cheese,
      fish and whole-grain foods, as well as coffee and alcohol consumption, were not
      significantly related to endometriosis. CONCLUSIONS: This study suggests a link
      between diet and risk of endometriosis.

PMID- 15254010
TI  - The recently identified type 2A juvenile haemochromatosis gene (HJV), a second
      candidate modifier of the C282Y homozygous phenotype.
AB  - The most common form of hereditary haemochromatosis is an adult-onset condition
      usually associated with the HFE C282Y/C282Y genotype. The phenotypic expression
      of this genotype is heterogeneous and depends on a complex interplay of genetic
      and non-genetic factors. The aim of the present study was to determine if
      mutations in the recently identified HJV gene were associated with more severe
      iron overload phenotypes in C282Y homozygous patients. From a cohort of 310 C282Y
      homozygous patients, we found nine (six males and three females) with an
      additional HJV missense mutation in the heterozygous state (S105L, E302K, N372D,
      R335Q or the previously described L101P and G320V). The iron indices of eight
      patients appeared to be more severe than those observed in C282Y homozygous
      patients of identical sex and similar age ranges. The mean serum ferritin
      concentration of the six males with an HJV mutation was significantly higher than
      that of C282Y homozygous males without an additional mutation [2350.3
      (sigma=1429.9) versus 1227.2 (sigma=1130.1) microg/l; P=0.0233, Student's t
      test]. We have recently reported that mutations in the gene that encodes hepcidin
      (HAMP) could explain one part of the C282Y/C282Y-related phenotypic heterogeneity
      by accentuating the iron burden. Our new data reveal that mutations in the HJV
      gene could be associated with a similar effect. Taken together, these results
      emphasize that a search for modifier genes could enable us to more precisely
      distinguish those C282Y homozygous patients with a higher risk to develop a
      severe iron overload and, consequently, clinical complications.

PMID- 15254011
TI  - Gene-Ontology analysis reveals association of tissue-specific 5' CpG-island genes
      with development and embryogenesis.
AB  - A key open question in the understanding of the biology of DNA methylation
      relates to the origin and function of CpG islands, stretches of GC-rich and
      relatively CpG-rich DNA sequence that often colocalize with promoter regions. All
      housekeeping, but also a substantial minority of tissue-specific genes are
      associated with the CpG islands. Limited experimental evidence suggests that CpG
      islands are associated with promoters or replication origins active during early
      development. Although this hypothesis is attractive for widely expressed genes,
      which would be expected to be expressed during early development, many tissue
      specific genes also contain CpG islands. In this work, we used a genome-wide Gene
      Ontology (GO)-based approach to analyze associations between GO terms and the
      presence of 5' CpG islands in human Reference Sequence (RefSeq) genes. We found
      that 19 of the 3849 GO terms with at least one annotated human sequence showed a
      highly significant association with the likelihood of 5' CpG islands being
      present in genes annotated to that term. In particular, the term 'development'
      showed a highly significantly increased proportion of 5' CpG island genes. The
      overrepresentation of 5' CpG island genes was even more significant for tissue
      specific RefSeqs annotated to development as well as many of its descendent
      terms. In addition, the proportion of expressed sequence tags from embryonic
      libraries amongst tissue-specific genes was twice as high for RefSeqs with 5' CpG
      islands as for those without CpG islands. These results provide strong support
      for previous speculations that early embryonic expression is associated with CpG
      islands.

PMID- 15254012
TI  - Epileptic-like convulsions associated with LIS-1 in the cytoskeletal control of
      neurotransmitter signaling in Caenorhabditis elegans.
AB  - Cortical malformations are a collection of disorders affecting brain development.
      Mutations in the LIS1 gene lead to a disorganized and smooth cerebral cortex
      caused by failure in neuronal migration. Among the clinical consequences of
      lissencephaly are mental retardation and intractable epilepsy. It remains unclear
      whether the seizures result from aberrant neuronal placement, disruption of
      intrinsic properties of neurons, or both. The nematode Caenorhabditis elegans
      offers an opportunity to study such convulsions in a simple animal with a defined
      nervous system. Here we show that convulsions mimicking epilepsy can be induced
      by a mutation in a C. elegans lis-1 allele (pnm-1), in combination with a
      chemical antagonist of gamma-aminobutyric acid (GABA) neurotransmitter signaling.
      Identical convulsions were obtained using C. elegans mutants defective in GABA
      transmission, whereas none of these mutants or the antagonist alone caused
      convulsions, indicating a threshold was exceeded in response to this combination.
      Crosses between pnm-1 and fluorescent marker strains designed to exclusively
      illuminate either the processes of GABAergic neurons or synaptic vesicles
      surprisingly showed no deviations in neuronal architecture. Instead, presynaptic
      defects in GABAergic vesicle distribution were clearly evident and could be
      phenocopied by RNAi directed against cytoplasmic dynein, a known LIS1 interactor.
      Furthermore, mutations in UNC-104, a neuronal-specific kinesin, and SNB-1, a
      synaptic vesicle-associated protein termed synaptobrevin, exhibit similar
      convulsion phenotypes following chemical induction. Taken together, these studies
      establish C. elegans as a system to investigate subtle cytoskeletal mechanisms
      regulating intrinsic neuronal activity and suggest that it may be possible to
      dissociate the epileptic consequences of lissencephaly from the more
      phenotypically overt cortical defects associated with neuronal migration.

PMID- 15254013
TI  - Identification of loci determining susceptibility to the lethal effects of
      amyloid precursor protein transgene overexpression.
AB  - Phenotypes produced by expression of human amyloid precursor protein (APP)
      transgenes vary depending on the genetic background of the mouse. FVB/N mice
      overexpressing human APP695 develop a central nervous system disorder and die
      prematurely, precluding development of Abeta peptide amyloid plaques. 129S6 mice
      are resistant to the lethal effects of APP overexpression, allowing sufficient
      levels of Abeta expression for the development of amyloid plaques and age
      dependent memory deficits. To identify the genes that determine susceptibility or
      resistance to APP we analyzed crosses involving FVB/NCr and 129S6.Tg2576 mice
      that overexpress 'Swedish' mutant (K670N, M671L) APP695. APP transgene-positive
      FVB129S6F1 (F1) mice are resistant to the lethal effects of APP overexpression,
      so FVBxF1 backcross and F2 intercross offspring were produced. Analysis of age of
      death as a quantitative trait revealed significant linkage to loci on proximal
      chromosome 14 and on chromosome 9; 129S6 alleles protect against the lethal
      effects of APP. Within the chromosome 14 interval are segments homologous to
      regions on human chromosome 10 that have been linked to late onset Alzheimer's
      disease or to levels of Abeta peptide in plasma. However, analysis of plasma
      Abeta peptide concentrations at 6 weeks in backcross offspring produced no
      significant linkage. Similarly, elevation of human Abeta peptide concentrations
      by expression of mutant presenilin transgenes did not increase the proportion of
      mice dying prematurely, suggesting that early death reflects effects of APP or
      fragments other than Abeta.

PMID- 15254014
TI  - The R172W mutation in peripherin/rds causes a cone-rod dystrophy in transgenic
      mice.
AB  - Peripherin/rds (P/rds) is a membrane glycoprotein essential for the photoreceptor
      outer segment disc morphogenesis and maintenance. More than half of the disease
      causing mutations in P/rds have been linked to different forms of macular
      dystrophy; the most common one is substitution of tryptophan for arginine at
      position 172 (R172W). Here we confirm the patient phenotype associated with the
      expression of R172W mutation in transgenic mice. Functional, structural and
      biochemical analyses showed that, while R172W P/rds is appropriately localized, a
      direct correlation exists between transgene expression levels and the
      onset/severity of the phenotype. In the wild-type background, both cone and rod
      photoreceptors' structure and function were significantly diminished, which
      indicates a dominant-negative, cone-rod defect. Whereas rds(+/-) mice maintained
      the normal cone function at early ages, cone responses in R172W/rds(+/-) mice
      were diminished to 41% of the wild-type level signifying a preferential damaging
      effect of the mutation on cones. Conversely, R172W/rds(+/-) mice showed a
      significant rescue of rod function and improvement of rod outer segment
      structure. Although rds(-/-) mice have no detectable rod or cone responses,
      R172W/rds(-/-) animals retained 30% of wild-type structure and rod function, but
      no significant rescue of cone function was detected at 1 month of age. No
      biochemical abnormalities were observed in complex formation and association with
      Rom-1; however, R172W protein was more sensitive to tryptic digestion, indicative
      of a change in protein conformation, possibly contributing to the cone-dominated
      phenotype. As the first animal model for P/rds-associated cone-rod dystrophy,
      R172W mice provide a valuable tool for studying the pathophysiology of P/rds
      associated human retinal dystrophies and the development of therapeutic
      strategies to intervene in these diseases.

PMID- 15254015
TI  - Disruption of muscle membrane and phenotype divergence in two novel mouse models
      of dysferlin deficiency.
AB  - Limb girdle muscular dystrophy type 2B and Miyoshi myopathy are clinically
      distinct forms of muscular dystrophy that arise from defects in the dysferlin
      gene. Here, we report two novel lines of dysferlin-deficient mice obtained by (a)
      gene targeting and (b) identification of an inbred strain, A/J, bearing a
      retrotransposon insertion in the dysferlin gene. The mutations in these mice were
      located at the 3' and 5' ends of the dysferlin gene. Both lines of mice lacked
      dysferlin and developed a progressive muscular dystrophy with histopathological
      and ultrastructural features that closely resemble the human disease. Vital
      staining with Evans blue dye revealed loss of sarcolemmal integrity in both lines
      of mice, similar to that seen in mdx and caveolin-3 deficient mice. However, in
      contrast to the latter group of animals, the dysferlin-deficient mice have an
      intact dystrophin glycoprotein complex and normal levels of caveolin-3. Our
      findings indicate that muscle membrane disruption and myofiber degeneration in
      dysferlinopathy were directly mediated by the loss of dysferlin via a new
      pathogenic mechanism in muscular dystrophies. We also show that the mutation in
      the A/J mice arose between the late 1970s and the early 1980s, and had become
      fixed in the production breeding stocks. Therefore, all studies involving the A/J
      mice or mice derived from A/J, including recombinant inbred, recombinant congenic
      and chromosome substitution strains, should take into account the dysferlin
      defect in these strains. These new dysferlin-deficient mice should be useful for
      elucidating the pathogenic pathway in dysferlinopathy and for developing
      therapeutic strategies.

PMID- 15254016
TI  - Structurally altered basement membranes and hydrocephalus in a type XVIII
      collagen deficient mouse line.
AB  - Type XVIII collagen/endostatin is known to be crucial for the eye, as witnessed
      by severe eye defects in Knobloch syndrome patients with mutations in this
      collagen and in Col18a1(-/-) mice. We show here that in a specific C57BL
      background, 20% of the Col18a1(-/-) mice developed hydrocephalus, and dilation of
      the brain ventricles was observed by MRI in all of the mutant mice. Significant
      broadening was observed in the epithelial basement membrane (BM) of the choroid
      plexuses (CP), its width being 86.4+/-10.52 nm, compared with 61.4+/-6.05 nm in
      wild-type mice. The CP epithelial cell morphology was balloon-shaped rather than
      cuboidal, and the microvilli of the apical surface of the CP epithelium contained
      more vacuoles in the null mice than in the wild-type, as also did the CP
      epithelial cells, which is suggestive of alterations in cerebrospinal fluid
      production. Analysis of BMs elsewhere in the body revealed a broadened epidermal
      BM in the Col18a1(-/-) mice, but this did not result in any apparent functional
      deficiencies. Moreover, markedly broadened BMs were found in the atrioventricular
      valves of the heart and in the kidney tubules, whereas the glomerular mesangial
      matrix of the kidneys was expanded in the mutant mice and serum creatinine levels
      were elevated, indicating alterations in kidney filtration capacity. We thus
      suggest that type XVIII collagen is a structurally important constituent of BMs,
      and that its absence can result in a variety of phenotypic alterations.

PMID- 15254017
TI  - Comparison of pathways controlling toxicity in the eye and brain in Drosophila
      models of human neurodegenerative diseases.
AB  - Most human neurodegenerative diseases have a number of common features, including
      adult onset, progressive degeneration of selected neuronal populations and
      formation of abnormal protein aggregates. Although these shared characteristics
      raise the possibility of conserved pathogenic mechanisms, the diverse clinical
      and pathological features of each disorder indicate significant differences. As a
      number of human neurodegenerative diseases have now been modeled in Drosophila,
      and genetic modifiers identified, we have been able to perform a genetic
      comparison of pathways controlling toxicity in these models. By directly
      comparing modifiers isolated in the models of polyglutamine diseases and in a
      Drosophila model of tauopathy, we find a final common pathway of cell death
      involving apoptosis. Among the polyglutamine diseases, protein folding and
      histone acetylation are common key mediators. In addition, two novel modifiers
      suggest shared pathways of toxicity among all the disorders. Cell-type
      specificity is a salient feature of all neurodegenerative diseases; however, most
      work to date in the Drosophila models have been performed in the retina.
      Therefore, we determined whether similar pathways of toxicity operate in neurons
      of the Drosophila brain. Many, but not all, retinal modifiers also modify
      toxicity in postmitotic neurons in the brain. Analysis of polyglutamine toxicity
      in the adult brain facilitated the identification of nicotinamide (vitamin B3), a
      vitamin with histone deacetylase inhibiting activity, as a potent suppressor of
      polyglutamine toxicity. These findings outline common pathways of neurotoxicity,
      demonstrate disease- and cell-type specific pathways and identify a common
      vitamin as a potential therapy in polyglutamine disorders.

PMID- 15254018
TI  - Differential expression of a novel ankyrin containing E3 ubiquitin-protein
      ligase, Hace1, in sporadic Wilms' tumor versus normal kidney.
AB  - We have analyzed the chromosome 6q21 breakpoint of a non-constitutional
      t(6;15)(q21;q21) rearrangement in sporadic Wilms' tumor. This identified a novel
      gene encoding a protein with six N-terminal ankyrin repeats linked to a C
      terminal HECT ubiquitin-protein ligase domain. We therefore designated this gene
      HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1).
      HACE1 is widely expressed in human tissues, including mature and fetal kidney. We
      show that Hace1 protein possesses intrinsic ubiquitin ligase activity, utilizes
      UbcH7 as a candidate partner E2 enzyme and localizes predominantly to the
      endoplasmic reticulum. Although the HACE1 locus was not directly interrupted by
      the translocation in the index Wilms' case, its expression was markedly lower in
      tumor tissue compared with adjacent normal kidney. Moreover, HACE1 expression was
      virtually undetectable in the SK-NEP-1 Wilms' tumor cell line and in four of five
      additional primary Wilms' tumor cases compared with patient-matched normal
      kidney. We found no evidence of HACE1 mutations or deletions, but
      hypermethylation of two upstream CpG islands correlates with low HACE1 expression
      in tumor samples. Our findings implicate Hace1 as a novel ubiquitin-protein
      ligase and demonstrate that its expression is very low in primary Wilms' tumors.

PMID- 15254019
TI  - Reduced cellular expression and activity of the P129T mutant of human fatty acid
      amide hydrolase: evidence for a link between defects in the endocannabinoid
      system and problem drug use.
AB  - Fatty acid amide hydrolase (FAAH) inactivates the endogenous cannabinoid
      (endocannabinoid) anandamide and related lipid transmitters in vivo. A single
      nucleotide polymorphism (SNP) in the human FAAH gene (385C to A) has recently
      been described that, in homozygous form, is over-represented in subjects with
      problem drug use. This SNP, which converts a conserved proline residue in FAAH to
      threonine (P129T), suggests a potential role for the FAAH-endocannabinoid system
      in regulating addictive behavior. Nonetheless, the impact of the 385A mutation on
      the biochemical and cellular function of FAAH remains unknown. Here, we report
      that T-lymphocytes isolated from patients homozygous for the P129T-FAAH variant
      express less than half of the FAAH protein and activity observed in wild-type
      (WT) lymphocytes. Transfected COS-7 cells also expressed significantly lower
      levels of P129T-FAAH compared with WT-FAAH, indicating that the aberrant
      expression of the former protein is not a cell type-specific phenomenon. A
      comparison of the transcription/translation efficiencies and cellular stabilities
      of WT- and P129T-FAAH proteins revealed that the reduced expression of the mutant
      enzyme is due to a post-translational mechanism that precedes productive folding.
      These findings indicate that the natural 385A SNP in the human FAAH gene produces
      a mutant enzyme with reduced cellular stability, thus fortifying a potential link
      between functional abnormalities in the endocannabinoid system and drug abuse and
      dependence.

PMID- 15254020
TI  - The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new
      substrates for the DDP1/TIMM8a-TIMM13 complex.
AB  - The biogenesis of the mitochondrial inner membrane is dependent on two distinct
      70 kDa protein complexes. TIMM8a partners with TIMM13 in the mitochondrial
      intermembrane space to form a 70 kDa complex and facilitates the import of the
      inner membrane substrate TIMM23. We have identified a new class of substrates,
      citrin and aralar1, which are Ca2+-binding aspartate/glutamate carriers (AGCs) of
      the mitochondrial inner membrane, using cross-linking and immunoprecipitation
      assays in isolated mitochondria. The AGCs function in the aspartate-malate NADH
      shuttle that moves reducing equivalents from the cytosol to the mitochondrial
      matrix. Mohr-Tranebjaerg syndrome (MTS/DFN-1, deafness/dystonia syndrome) results
      from a mutation in deafness/dystonia protein 1/translocase of mitochondrial inner
      membrane 8a (DDP1/TIMM8a) and loss of the 70 kDa complex. A lymphoblast cell line
      derived from an MTS patient had decreased NADH levels and defects in
      mitochondrial protein import. Protein expression studies indicate that DDP1 and
      TIMM13 show non-uniform expression in mammals, and expression is prominent in the
      large neurons in the brain, which is in agreement with the expression pattern of
      aralar1. Thus, insufficient NADH shuttling, linked with changes in Ca2+
      concentration, in sensitive cells of the central nervous system might contribute
      to the pathologic process associated with MTS.

PMID- 15254021
TI  - Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a
      target of the Pou4f3 deafness gene.
AB  - Pou4f3 (Brn3.1, Brn3c) is a class IV POU domain transcription factor that has a
      central function in the development of all hair cells in the human and mouse
      inner ear sensory epithelia. A mutation of POU4F3 underlies human autosomal
      dominant non-syndromic progressive hearing loss DFNA15. Through a comparison of
      inner ear gene expression profiles of E16.5 wild-type and Pou4f3 mutant deaf mice
      using a high density oligonucleotide microarray, we identified the gene encoding
      growth factor independence 1 (Gfi1) as a likely in vivo target gene regulated by
      Pou4f3. To validate this result, we performed semi-quantitative RT-PCR and in
      situ hybridizations for Gfi1 on wild-type and Pou4f3 mutant mice. Our results
      demonstrate that a deficiency of Pou4f3 leads to a statistically significant
      reduction in Gfi1 expression levels and that the dynamics of Gfi1 mRNA abundance
      closely follow the pattern of expression for Pou4f3. To examine the role of Gfi1
      in the pathogenesis of Pou4f3-related deafness, we performed comparative analyses
      of the embryonic inner ears of Pou4f3 and Gfi1 mouse mutants using
      immunohistochemistry and scanning electron microscopy. The loss of Gfi1 results
      in outer hair cell degeneration, which appears comparable to that observed in
      Pou4f3 mutants. These results identify Gfi1 as the first downstream target of a
      hair cell specific transcription factor and suggest that outer hair cell
      degeneration in Pou4f3 mutants is largely or entirely a result of the loss of
      expression of Gfi1.

PMID- 15254022
TI  - Pet animals as reservoirs of antimicrobial-resistant bacteria.
AB  - Pet animal numbers have substantially increased in modern society and attention
      is increasingly devoted to pet welfare. Because of these changes, antimicrobial
      agents are frequently used in small animal veterinary practice, often including
      antimicrobial preparations used in human medicine, with heavy use of broad
      spectrum agents such as aminopenicillins plus clavulanic acid, cephalosporins and
      fluoroquinolones. Several longitudinal studies conducted at veterinary hospitals
      have indicated that resistance to various antimicrobial agents has emerged
      amongst pet animal isolates of Staphylococcus intermedius, Escherichia coli and
      other bacteria, including species with a potential for zoonotic transmission and
      resistance phenotypes of clinical interest, such as methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant
      Salmonella Typhimurium DT104. Based on a review of the current literature, the
      role of pets in the dissemination of antimicrobial resistance has been given
      little attention when compared with that of food animals. A marked contrast is
      evident between the current policies on antimicrobial usage in food and companion
      animals. Apart from a few countries where limited data on antimicrobial usage and
      occurrence of resistance in bacteria from pet animals are provided, national
      surveillance programmes only focus on food animals. However, data on pet animals
      are clearly needed for guiding antimicrobial use policy in small animal
      veterinary practice as well as for assessing the risk of transmission of
      antimicrobial resistance to humans.

PMID- 15254023
TI  - Inhibition of respiratory syncytial virus by RhoA-derived peptides: implications
      for the development of improved antiviral agents targeting heparin-binding
      viruses.
AB  - The respiratory syncytial virus (RSV) fusion glycoprotein (F) can interact with
      the small intracellular GTPase RhoA, and peptides derived from RhoA inhibit RSV
      replication. These observations initially suggested that RhoA-derived peptides
      might inhibit RSV replication by disrupting an in vivo interaction between RSV F
      and RhoA. However, recent data indicate that the antiviral activity of RhoA
      derived peptides is not due to competitive inhibition of an hypothesized F-RhoA
      interaction, but is rather a function of the peptides' intrinsic biophysical
      properties. We summarize here what is known about the mechanism of RSV inhibition
      by these peptides and give our opinion regarding the potential implications of
      this work with regards to RSV biology, and to the development of antiviral agents
      targeting RSV and other enveloped viruses.

PMID- 15254024
TI  - Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics
      and pharmacodynamics in blood, CSF and semen.
AB  - OBJECTIVES: To evaluate the steady-state blood plasma (BP), CSF and seminal
      plasma (SP) pharmacokinetics (PK) of twice-daily indinavir 400 mg and
      lopinavir/ritonavir. METHODS: Ten HIV-1-positive men on lopinavir/ritonavir
      participated in a PK study. PK sampling was performed before and 2 weeks after
      adding indinavir to lopinavir/ritonavir-containing regimens. BP, CSF and SP RNA
      levels, CD4 counts and blood chemistry were checked at baseline and 2 weeks after
      indinavir. RESULTS: At baseline: lopinavir parameters (n=10) in BP were within
      expected levels. Median lopinavir trough concentrations (n=5) in CSF and SP were
      below the limit of detection (BLD) (i.e. <10 ng/mL) and 248 ng/mL (range 96
      2777), respectively. After indinavir: lopinavir C(max), C(min) and AUC(0-12)
      increased by 9%, 46% and 20%, respectively (P<0.32, P<0.32 and P<0.20). In two of
      four men lopinavir concentrations in CSF were detectable at 27 and 29 ng/mL.
      Median SP lopinavir concentration was 655 ng/mL (20-2734). Median indinavir PK
      parameters were C(max) 3365 ng/mL (range 2130-5194), C(min) 293 ng/mL (14-766),
      T(max) 2.25 h (1-3), AUC(0-12) 22452 ng/mL.h (11243-33661), and t(1/2) 2.8 h (1.4
      3.7). Median indinavir concentrations in CSF and SP were 39 ng/mL (21-86) and 592
      ng/mL (96-983). Two of eight men who initially had detectable BP viral load (VL)
      became BLD (<50 copies/mL) after the addition of indinavir, and in 2/4 men with
      low-level viraemia in SP (BPVL BLD) their SPVL became BLD after addition of
      indinavir. CONCLUSIONS: Adding indinavir 400 mg twice daily to
      lopinavir/ritonavir-containing regimens did not significantly alter the median
      lopinavir PK parameters. However, wide interpatient variability in lopinavir
      concentrations was seen. In contrast plasma indinavir levels were >80 ng/mL in
      seven of eight plasma samples, and all CSF and semen samples collected.

PMID- 15254025
TI  - In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta
      lactamase inhibitor.
AB  - OBJECTIVES: Production of beta-lactamases is the main mechanism of beta-lactam
      resistance in Gram-negative bacteria. Despite the current use of clavulanic acid,
      sulbactam and tazobactam, the prevalence of class A and class C enzymes is
      increasing worldwide, demanding new beta-lactamase inhibitors. Here we report the
      antimicrobial properties of AVE1330A, a representative of a novel class of
      bridged bicyclico[3.2.1]diazabicyclo-octanones in combination with ceftazidime.
      MATERIALS AND METHODS: IC(50) and kinetic parameters of the hydrolysis reaction
      were used to characterize beta-lactamase inhibition by AVE1330A. MICs for >600
      strains were determined with the combination ceftazidime/AVE1330A at a fixed
      ratio of 4:1. RESULTS: IC(50)s of AVE1330A for TEM-1 and P99 enzymes were 0.0023
      mg/L (8 nM) and 0.023 mg/L (80 nM), compared with 0.027 mg/L (130 nM) and 205.1
      mg/L (1 x 10(6) nM) of clavulanic acid and 0.013 mg/L (40 nM) and 1.6 mg/L (5000
      nM) of tazobactam. A highly stable covalent complex led to a low turnover of
      AVE1330A. MICs of ceftazidime/AVE1330A for Enterobacteriaceae were at least eight
      fold lower than those of ceftazidime alone. All of the Escherichia coli,
      Klebsiella pneumoniae, Citrobacter and Proteus mirabilis strains, including
      ceftazidime-resistant isolates, were inhibited at 4-8 mg/L. Only 2 mg/L were
      required to inhibit other Proteeae, Enterobacter, Salmonella and Serratia.
      CONCLUSION: The combination of ceftazidime with AVE1330A exhibited broad-spectrum
      activity against Ambler class A- and class C-producing Enterobacteriaceae.

PMID- 15254026
TI  - Tolerance of Pseudomonas aeruginosa to Melaleuca alternifolia (tea tree) oil is
      associated with the outer membrane and energy-dependent cellular processes.
AB  - OBJECTIVES: The essential oil of Melaleuca alternifolia (tea tree oil) and its
      components have antimicrobial activity against a wide range of Gram-positive and
      Gram-negative bacteria, fungi and viruses. The mechanism(s) by which Pseudomonas
      aeruginosa NCTC 10662 maintains a decreased susceptibility to tea tree oil and
      components was investigated. RESULTS: Ethylene diamine tetraacetic acid enhanced
      the antimicrobial activity of tea tree oil and terpinen-4-ol against stationary
      phase P. aeruginosa while polymyxin B nonapeptide enhanced the activity of tea
      tree oil and gamma-terpinene. Pre-treatment with the protonophore carbonyl
      cyanide m-chlorophenylhydrazone increased the susceptibility of exponential phase
      cells to sub-inhibitory concentrations of tea tree oil, terpinen-4-ol and gamma
      terpinene, indicating that intrinsic tolerance to tea tree oil and components is
      substantially energy dependent. CONCLUSIONS: Increased tolerance to tea tree oil
      in P. aeruginosa is directly related to the barrier and energy functions of the
      outer membrane, and may involve efflux systems.

PMID- 15254027
TI  - Increasing in vitro resistance to fluconazole in Cryptococcus neoformans
      Cambodian isolates: April 2000 to March 2002.
AB  - OBJECTIVES: Cryptococcal meningitis is the third-most-common opportunistic
      infection in HIV patients in Cambodia. Hospitalized patients were given
      amphotericin B for initial therapy followed by fluconazole for maintenance
      therapy. The antifungal drug susceptibility of Cryptococcus neoformans isolated
      from cerebrospinal fluid (CSF) was determined. METHODS: Isolates of C. neoformans
      were collected during active laboratory-based surveillance, the first batch from
      April 2000 to March 2001 (134 new cases), the second batch from April 2001 to
      March 2002 (268 new cases). Etest strips were used to determine the MICs of
      amphotericin B and fluconazole. The antigenic agglutination slide test was used
      for serotyping. RESULTS: The MIC(50)s and MIC(90)s of fluconazole changed
      significantly from year 2000 to 2002; the MIC(50)s increased from 4 to 12 mg/L,
      and the MIC(90)s from 12 to 96 mg/L. For amphotericin B, the MIC(50)s and
      MIC(90)s remained stable. Moreover, in the second batch, fluconazole MICs were
      >/=256 mg/L for 20 isolates. By serotyping, it was found that 98.5% of the
      isolates were serotype A. CONCLUSIONS: C. neoformans strains isolated from CSF of
      AIDS patients in Cambodia remain susceptible in vitro to amphotericin B. These
      strains are less susceptible in vitro to fluconazole, 2.5% being resistant in the
      first year and 14% in the second year of study. Nevertheless, in vitro resistance
      of C. neoformans to fluconazole appeared to be linked to extended maintenance
      treatments.

PMID- 15254028
TI  - Outcome of inappropriate initial antimicrobial treatment in patients with
      methicillin-resistant Staphylococcus aureus bacteraemia.
AB  - OBJECTIVE: To determine the impact of delayed treatment of methicillin-resistant
      Staphylococcus aureus bacteraemia (MRSA bacteraemia) on mortality. PATIENTS AND
      METHODS: We used two different and complementary approaches: a retrospective
      cohort study and a matched case-control study. Of the total of all patients with
      S. aureus bacteraemia in a tertiary hospital over a 4 year period, 127 patients
      with MRSA bacteraemia were enrolled in the cohort study. The cases for the case
      control study were defined as patients who received appropriate empirical
      treatment for MRSA bacteraemia; the controls, who were patients who received
      inappropriate empirical treatment for MRSA bacteraemia, were selected according
      to the matching variables of age, sex, severity of underlying illness,
      classification of main underlying disease and prior hospital stay. On the 14
      point matching scale that was used to select the best controls, the average score
      (+/-S.D.) of the 30 controls was 11.2 (+/-2.0). RESULTS: In the cohort study, the
      difference in S. aureus bacteraemia-related mortality between appropriate (30%,
      9/30) and inappropriate (39%, 38/97) empirical treatment was not significant
      (P=0.36). In addition, multivariate analysis did not indicate that inappropriate
      empirical treatment was associated with mortality when independent predictors for
      mortality were considered (adjusted OR 1.1, 95% CI 0.4-3.1). In the case-control
      study, S. aureus bacteraemia-related mortality in case patients was 30% (9/30)
      and in control patients 33% (10/30) (P>0.99, McNemar's test). In four of the nine
      discordant pairs, the case patients died whereas the control patients lived.
      CONCLUSIONS: Our data suggest that an initial delay of 2 days in the use of
      appropriate antibiotics, especially of vancomycin or other glycopeptides, before
      the preliminary microbiological report may not adversely affect the outcome in
      patients with MRSA bacteraemia.

PMID- 15254029
TI  - Analysis of sequence variation among smeDEF multi drug efflux pump genes and
      flanking DNA from defined 16S rRNA subgroups of clinical Stenotrophomonas
      maltophilia isolates.
AB  - OBJECTIVES: To determine the level of variation in the smeDEF efflux pump and
      smeT transcriptional regulator genes among three defined 16S rRNA sequence
      subgroups of clinical Stenotrophomonas maltophilia isolates. METHODS: smeDEF
      sequencing used a PCR genome walking approach. Determination of the sequence
      surrounding smeDEF used a flanking primer PCR method and specific primers
      anchored in smeD or smeF together with random primers. RESULTS: smeDEF is
      chromosomal and located in the same position in the chromosome in all three
      subgroups of isolates. Flanking smeD is a gene, smeT, encoding a putative
      transcriptional repressor for smeDEF. Variation at these loci among the isolates
      is considerably lower (up to 10%) than at intrinsic beta-lactamase loci (up to
      30%) in the same isolates, implying greater functional constraint. The smeD-smeT
      intergenic region contains a highly conserved section, which maps with previously
      predicted promoter/operator regions, and a hypervariable untranslated region,
      which can be used to subgroup clinical isolates. CONCLUSIONS: These data provide
      further evidence that it is possible to group clinical isolates of the inherently
      variable species, S. maltophilia, based on genotypic properties. Isolate D457, in
      which most work concerning smeDEF expression has been performed, does not fall
      into S. maltophilia subgroup A, which is the most typical.

PMID- 15254030
TI  - Monitoring of florfenicol susceptibility among bovine and porcine respiratory
      tract pathogens collected in Germany during the years 2002 and 2003.

PMID- 15254031
TI  - Glutathione is required to regulate the formation of native disulfide bonds
      within proteins entering the secretory pathway.
AB  - The formation of native disulfide bonds is an essential event in the folding and
      maturation of proteins entering the secretory pathway. For native disulfides to
      form efficiently an oxidative pathway is required for disulfide bond formation
      and a reductive pathway is required to ensure isomerization of non-native
      disulfide bonds. The oxidative pathway involves the oxidation of substrate
      proteins by PDI, which in turn is oxidized by endoplasmic reticulum oxidase
      (Ero1). Here we demonstrate that overexpression of Ero1 results in the
      acceleration of disulfide bond formation and correct protein folding. In
      contrast, lowering the levels of glutathione within the cell resulted in
      acceleration of disulfide bond formation but did not lead to correct protein
      folding. These results demonstrate that lowering the level of glutathione in the
      cell compromises the reductive pathway and prevents disulfide bond isomerization
      from occurring efficiently, highlighting the crucial role played by glutathione
      in native disulfide bond formation within the mammalian endoplasmic reticulum.

PMID- 15254032
TI  - Apolipoprotein B-containing lipoprotein particle assembly: lipid capacity of the
      nascent lipoprotein particle.
AB  - We previously proposed that the N-terminal 1000-residue betaalpha(1) domain of
      apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey
      lipovitellin. In support of this "lipid pocket" hypothesis, we demonstrated that
      apoB:1000 (residues 1-1000) is secreted by a stable transformant of McA-RH7777
      cells as a monodisperse particle with high density lipoprotein 3 (HDL(3))
      density. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the
      sequence homologous to lipovitellin, was secreted as a particle considerably more
      dense than HDL(3). In the present study we have determined the stoichiometry of
      the lipid component of the apoB:931 and apoB:1000 particles. The secreted
      [(3)H]glycerol-labeled apoB:1000 particles, isolated by nondenaturing gradient
      gel electrophoresis, contained 50 phospholipid (PL) and 11 triacylglycerol (TAG)
      molecules/particle. In contrast, apoB:931 particles contained only a few
      molecules of PL and were devoid of TAG. The unlabeled apoB:1000 particles,
      isolated by immunoaffinity chromatography, contained 56 PL, 8 TAG, and 7
      cholesteryl ester molecules/particle. The surface to core lipid ratio of
      apoB:1000-containing particles was approximately 4:1 and was not affected by
      oleate supplementation. Although very small amounts of microsomal triglyceride
      transfer protein (MTP) were associated with apoB:1000 particles, it never
      approached a 1:1 molar ratio of MTP to apoB. These results support a model in
      which (i) the first 1000 amino acid residues of apoB are competent to complete
      the lipid pocket without a structural requirement for MTP; (ii) a portion, or
      perhaps all, of the amino acid residues between 931 and 1000 of apoB-100 are
      critical for the formation of a stable, bulk lipid-containing nascent lipoprotein
      particle, and (iii) the lipid pocket created by the first 1000 residues of apoB
      100 is PL-rich, suggesting a small bilayer type organization and has a maximum
      capacity on the order of 50 molecules of phospholipid.

PMID- 15254033
TI  - Endosomes, glycosomes, and glycosylphosphatidylinositol catabolism in Leishmania
      major.
AB  - Glycosylphosphatidylinositols (GPIs) serve as membrane anchors of polysaccharides
      and proteins in the protozoan parasite Leishmania major. Free GPIs that are not
      attached to macromolecules are present in L. major as intermediates of protein
      GPI and polysaccharide-GPI synthesis or as terminal glycolipids. The importance
      of the intracellular location of GPIs in vivo for functions of the glycolipids is
      not appreciated. To examine the roles of intracellular free GPI pools for
      attachment to polypeptide, a GPI-specific phospholipase C (GPI-PLCp) from
      Trypanosoma brucei was used to probe trafficking of GPI pools inside L. major.
      The locations of GPIs were determined, and their catabolism by GPI-PLCp was
      analyzed with respect to the intracellular location of the enzyme. GPIs
      accumulated on the endo-lysosomal system, where GPI-PLCp was also detected. A
      peptide motif [CS][CS]-x(0,2)-G-x(1)-C-x(2,3)-S-x(3)-L formed part of an endosome
      targeting signal for GPI-PLCp. Mutations of the endosome targeting motif caused
      GPI-PLCp to associate with glycosomes (peroxisomes). Endosomal GPI-PLCp caused a
      deficiency of protein-GPI in L. major, whereas glycosomal GPI-PLCp failed to
      produce the GPI deficiency. We surmise that (i) endo-lysosomal GPIs are important
      for biogenesis of GPI-anchored proteins in L. major; (ii) sequestration of GPI
      PLCp to glycosomes protects free protein-GPIs from cleavage by the phospholipase.
      In T. brucei, protein-GPIs are concentrated at the endoplasmic reticulum,
      separated from GPI-PLCp. These observations support a model in which glycosome
      sequestration of a catabolic GPI-PLCp preserves free protein-GPIs in vivo.

PMID- 15254034
TI  - Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid
      metabolism.
AB  - NADPH is an essential cofactor for many enzymatic reactions including glutathione
      metabolism and fat and cholesterol biosynthesis. We have reported recently an
      important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in
      cellular defense against oxidative damage by providing NADPH needed for the
      regeneration of reduced glutathione. However, the role of cytosolic NADP(+)
      dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for
      the first time that IDPc plays a critical role in fat and cholesterol
      biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme
      activity and its protein content were increased in parallel in a time-dependent
      manner. Increased expression of IDPc by stable transfection of IDPc cDNA
      positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc
      expression by an antisense IDPc vector retarded adipogenesis. Furthermore,
      transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia,
      and obesity. In the epididymal fat pads of the transgenic mice, the expressions
      of adipocyte-specific genes including peroxisome proliferator-activated receptor
      gamma were markedly elevated. The hepatic and epididymal fat pad contents of
      acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower,
      whereas the total triglyceride and cholesterol contents were markedly higher in
      the liver and serum of transgenic mice compared with those measured in wild type
      mice, suggesting that the consumption rate of those lipogenic precursors needed
      for fat biosynthesis must be increased by elevated IDPc activity. Taken together,
      our findings strongly indicate that IDPc would be a major NADPH producer required
      for fat and cholesterol synthesis.

PMID- 15254035
TI  - A model of myosin V processivity.
AB  - Cytoplasmic transport is mediated by a group of molecular motors that typically
      work in isolation, under conditions where they must move their cargos long
      distances without dissociating from their tracks. This processive behavior
      requires specific adaptations of motor enzymology to meet these unique
      physiologic demands. One of these involves the ability of the two heads of a
      processive motor to communicate their structural states to each other. In this
      study, we examine a processive motor from the myosin superfamily myosin V. We
      have measured the kinetics of nucleotide release, of phosphate release, and of
      the weak-to-strong transition, as this motor interacts with actin, and we have
      used these studies to develop a model of how myosin V functions as a transport
      motor. Surprisingly, both heads release phosphate rapidly upon the initial
      encounter with an actin filament, suggesting that there is little or no
      intramolecular strain associated with this step. However, ADP release can be
      affected by both forward and rearward strain, and under steady-state conditions
      it is essentially prevented in the lead head until the rear head detaches. Many
      of these features are remarkably like those underlying the processive movement of
      kinesin on microtubules, supporting our hypothesis that different molecular
      motors satisfy the requirement for processive movement in similar ways,
      regardless of their particular family of origin.

PMID- 15254036
TI  - Myosin VI steps via a hand-over-hand mechanism with its lever arm undergoing
      fluctuations when attached to actin.
AB  - Myosin VI is a reverse direction myosin motor that, as a dimer, moves
      processively on actin with an average center-of-mass movement of approximately 30
      nm for each step. We labeled myosin VI with a single fluorophore on either its
      motor domain or on the distal of two calmodulins (CaMs) located on its putative
      lever arm. Using a technique called FIONA (fluorescence imaging with one
      nanometer accuracy), step size was observed with a standard deviation of <1.5 nm,
      with 0.5-s temporal resolution, and observation times of minutes. Irrespective of
      probe position, the average step size of a labeled head was approximately 60 nm,
      strongly supporting a hand-over-hand model of motility and ruling out models in
      which the unique myosin VI insert comes apart. However, the CaM probe displayed
      large spatial fluctuations (presence of ATP but not ADP or no nucleotide) around
      the mean position, whereas the motor domain probe did not. This supports a model
      of myosin VI motility in which the lever arm is either mechanically uncoupled
      from the motor domain or is undergoing reversible isomerization for part of its
      motile cycle on actin.

PMID- 15254037
TI  - The Pleckstrin homology domain of CK2 interacting protein-1 is required for
      interactions and recruitment of protein kinase CK2 to the plasma membrane.
AB  - CKIP-1 is a recently identified interaction partner of protein kinase CK2 with a
      number of protein-protein interaction motifs, including an N-terminal pleckstrin
      homology domain. To test the hypothesis that CKIP-1 has a role in targeting CK2
      to specific locations, we examined the effects of CKIP-1 on the localization of
      CK2. These studies demonstrated that CKIP-1 can recruit CK2 to the plasma
      membrane. Furthermore, the pleckstrin homology domain of CKIP-1 was found to be
      required for interactions with CK2 and for the recruitment of CK2 to the plasma
      membrane. In this regard, point mutations in this domain abolish membrane
      localization and compromise interactions with CK2. In addition, replacement of
      the pleckstrin homology domain with a myristoylation signal was insufficient to
      elicit any interaction with CK2. An investigation of the lipid binding of CKIP-1
      reveals that it has broad specificity. A comparison with other pleckstrin
      homology domains revealed that the pleckstrin homology domain of CKIP-1 is
      distinct from other defined classes of pleckstrin homology domains. Finally,
      examination of CK2alpha for a region that mediates interactions with CKIP-1
      revealed a putative HIKE domain, a complex motif found exclusively in proteins
      that bind pleckstrin homology domains. However, mutations within this motif were
      not able to abolish CKIP-1-CK2 interactions suggesting that this motif by itself
      may not be sufficient to mediate interactions. Overall, these results provide
      novel insights into how CK2, a predominantly nuclear enzyme, is targeted to the
      plasma membrane, and perhaps more importantly how it may be regulated.

PMID- 15254038
TI  - Alternative polyadenylation results in a truncated daf-4 BMP receptor that
      antagonizes DAF-7-mediated development in Caenorhabditis elegans.
AB  - The DAF-4 receptor kinase, which promotes larval development, is encoded by a 2.9
      kb mRNA transcribed from the only type II TGF-beta/BMP receptor gene in
      Caenorhabditis elegans. Here we report that alternative polyadenylation in intron
      5 of daf-4 results in a 2.0 kb mRNA that encodes an open reading frame including
      only the N-terminal secretion signal and ligand-binding domains, and not the
      transmembrane or kinase domains, of DAF-4. Northern blots and real-time RT-PCR
      amplifications using RNA samples from developmentally staged animals show that
      expression levels of both the 2.9 kb and 2.0 kb transcripts are relatively
      constant, and their abundances similar, except for the transition between non
      dauer and dauer stages. In dauer larvae, the steady-state level of the 2.0 kb
      mRNA increases more than 10-fold and exceeds the 2.9 kb transcript, coincident
      with an absence of signaling from DAF-4. Transgenic expression of a recombinant
      daf-4 transgene that encodes only the 2.0 kb mRNA enhances the Daf-c phenotype of
      a daf-4 hypomorph, whereas the same transgene with a nonsense mutation does not.
      These data suggest that a polypeptide encoded by the 2.0 kb transcript can
      function as an antagonist of full-length DAF-4 signaling. Alternative processing
      of type II receptor transcripts to generate an antagonist is a novel mechanism
      for negative regulation of a TGF-beta signaling pathway.

PMID- 15254039
TI  - The conformation of the activation peptide of protein C is influenced by Ca2+ and
      Na+ binding.
AB  - Previous studies have suggested that the conformation of the activation peptide
      of protein C is influenced by the binding of Ca(2+). To provide direct evidence
      for the linkage between Ca(2+) binding and the conformation of the activation
      peptide, we have constructed a protein C mutant in the gamma-carboxyglutamic acid
      domainless form in which the P1 Arg(169) of the activation peptide is replaced
      with the fluorescence reporter Trp. Upon binding of Ca(2+), the intrinsic
      fluorescence of the mutant decreases approximately 30%, as opposed to only 5% for
      the wild-type, indicating that Trp(169) is directly influenced by the divalent
      cation. The K(d) of Ca(2+) binding for the mutant protein C was impaired
      approximately 4-fold compared with wild-type. Interestingly, the conformation of
      the activation peptide was also found to be sensitive to the binding of Na(+),
      and the affinity for Na(+) binding increased approximately 5-fold in the presence
      of Ca(2+). These findings suggest that Ca(2+) changes the conformation of the
      activation peptide of protein C and that protein C is also capable of binding
      Na(+), although with a weaker affinity compared with the mature protease. The
      mutant protein C can no longer be activated by thrombin but remarkably it can be
      activated efficiently by chymotrypsin and by the thrombin mutant D189S.
      Activation of the mutant protein C by chymotrypsin proceeds at a rate comparable
      to the activation of wild-type protein C by the thrombin-thrombomodulin complex.

PMID- 15254040
TI  - The tumor suppressor protein p16(INK4a) and the human papillomavirus oncoprotein
      58 E7 are naturally occurring lysine-less proteins that are degraded by the
      ubiquitin system. Direct evidence for ubiquitination at the N-terminal residue.
AB  - Conjugation of ubiquitin to an internal lysine is the initial step in the
      degradation of the majority of the substrates of the ubiquitin system. For
      several substrates, it has been shown that the first ubiquitin moiety is
      conjugated to the N-terminal residue. In all these substrates, however, the
      internal lysines also played a role in modulating their stability. To better
      understand the physiological significance of this novel mode of modification, it
      was important to identify proteins in which degradation is completely dependent
      on N-terminal ubiquitination. Also, although the experimental evidence for N
      terminal ubiquitination is rather strong, nevertheless, it has remained indirect.
      Here we demonstrate that an important group of proteins that are targeted via N
      terminal ubiquitination are the naturally occurring lysine-less proteins such as
      the human papillomavirus (HPV)-58 E7 oncoprotein and the cell cycle inhibitor and
      tumor suppressor p16(INK4a). For these proteins, the only residue that can be
      targeted is the N-terminal residue. Interestingly, p16(INK4a) is degraded in a
      cell density-dependent manner. Importantly, we provide for the first time direct
      evidence for N-terminal ubiquitination. Analysis of tryptic digest of the
      ubiquitin conjugate of HPV-58 E7 revealed a fusion peptide that is composed of
      the C-terminal domain of ubiquitin and the N-terminal domain of E7. With the
      abundance of native lysine-less proteins, among which are important viral and
      cell regulators, this novel mode of protein targeting has implications for both
      physiological and pathophysiological processes.

PMID- 15254041
TI  - Redundant mechanisms are used by Ssn6-Tup1 in repressing chromosomal gene
      transcription in Saccharomyces cerevisiae.
AB  - The Ssn6-Tup1 corepressor complex regulates many genes in Saccharomyces
      cerevisiae. Three mechanisms have been proposed to explain its repression
      functions: 1) nucleosome positioning by binding histone tails; 2) recruitment of
      histone deacetylases; and 3) direct interference with the general transcription
      machinery or activators. It is unclear if Ssn6-Tup1 utilizes each of these
      mechanisms at a single gene in a redundant manner or each individually at
      different loci. A systematic analysis of the contribution of each mechanism at a
      native promoter has not been reported. Here we employed a genetic strategy to
      analyze the contributions of nucleosome positioning, histone deacetylation, and
      Mediator interference in the repression of chromosomal Tup1 target genes in vivo.
      We exploited the fact that Ssn6-Tup1 requires the ISW2 chromatin remodeling
      complex to establish nucleosome positioning in vivo to disrupt chromatin
      structure without affecting other Tup1 repression functions. Deleting ISW2, the
      histone deacetylase gene HDA1, or genes encoding Mediator subunits individually
      caused slight or no derepression of RNR3 and HUG1. However, when Mediator
      mutations were combined with Deltaisw2 or Deltahda1 mutations, enhanced
      transcription was observed, and the strongest level of derepression was observed
      in triple Deltaisw2/Deltahda1/Mediator mutants. The increased transcription in
      the mutants was not due to the loss of Tup1 at the promoter and correlated with
      increased TBP cross-linking to promoters. Thus, Tup1 utilizes multiple redundant
      mechanisms to repress transcription of native genes, which may be important for
      it to act as a global corepressor at a wide variety of promoters.

PMID- 15254043
TI  - Structure of the Neisseria meningitidis outer membrane PilQ secretin complex at
      12 A resolution.
AB  - The bacterial pathogen Neisseria meningitidis expresses long, thin, retractile
      fibers (called type IV pili) from its cell surface and uses these adhesive
      structures to mediate primary attachment to epithelial cells during host
      colonization and invasion. PilQ is an outer membrane protein complex that is
      essential for the translocation of these pili across the outer membrane. Here, we
      present the structure of the PilQ complex determined by cryoelectron microscopy
      to 12 A resolution. The dominant feature of the structure is a large central
      cavity, formed by four arm features that spiral upwards from a squared ring base
      and meet to form a prominent cap region. The cavity, running through the center
      of the complex, is continuous and is effectively sealed at both the top and
      bottom. Analysis of the complex using self-orientation and by examination of two
      dimensional crystals indicates a strong C4 rotational symmetry, with a much
      weaker C12 rotational symmetry, consistent with PilQ possessing true C4 symmetry
      with C12 quasi-symmetry. We therefore suggest that the complex is a
      homododecamer, formed by association of 12 PilQ polypeptide chains into a
      tetramer of trimers. The structure of the PilQ complex, with its large and well
      defined central chamber, suggests that it may not function solely as a passive
      portal in the outer membrane, but could be actively involved in mediating pilus
      assembly or modification.

PMID- 15254042
TI  - Cargo sequences are important for Som1p-dependent signal peptide cleavage in
      yeast mitochondria.
AB  - The inner membrane protease (IMP) has two catalytic subunits, Imp1p and Imp2p,
      that exhibit nonoverlapping substrate specificity in mitochondria of the yeast
      Saccharomyces cerevisiae. The IMP also has at least one noncatalytic subunit,
      Som1p, which is required to cleave signal peptides from a subset of Imp1p
      substrates. To understand how Som1p mediates Imp1p substrate specificity, we
      addressed the possibility that Som1p functions as a molecular chaperone, which
      binds to specific substrates and directs them to the catalytic site. Our results
      show that cargo sequences attached to the signal peptide are important for Som1p
      dependent presequence cleavage; however, no specific cargo sequence is required.
      Indeed, we show that a substrate normally destined for Imp2p is cleaved in a
      Som1p-dependent manner when the substrate is directed to Imp1p. These results
      argue against the notion that Som1p is a molecular chaperone. Instead, we propose
      that the cargo of some Imp1p substrates can assume a conformation incompatible
      with presequence cleavage. Som1p could thus act through Imp1p to improve cleavage
      efficiency early during substrate maturation.

PMID- 15254044
TI  - Phospholipid barrier to fibrinolysis: role for the anionic polar head charge and
      the gel phase crystalline structure.
AB  - The massive presence of phospholipids is demonstrated in frozen sections of human
      arterial thrombi. Purified platelet phospholipids and synthetic phospholipids
      retard in vitro tissue-type plasminogen activator (tPA)-induced fibrinolysis
      through effects on plasminogen activation and plasmin function. The inhibition of
      plasminogen activation on the surface of fibrin correlates with the fraction of
      anionic phospholipid. The phospholipids decrease the amount of tPA penetrating
      into the clot by 75% and the depth of the reactive surface layer occupied by the
      activator by up to 30%, whereas for plasmin both of these parameters decrease by
      approximately 50%. The phospholipids are not only a diffusion barrier, they also
      bind the components of the fibrinolytic system. Isothermal titration calorimetry
      shows binding characterized with dissociation constants in the range 0.35-7.64
      microm for plasmin and tPA (lower values with more negative phospholipids). The
      interactions are endothermic and thermodynamically driven by an increase in
      entropy, probably caused by the rearrangements in the ordered gel structure of
      the phospholipids (in line with the stronger inhibition at gel phase temperatures
      compared with liquid crystalline phase temperatures). These findings show a
      phospholipid barrier, which should be overcome during lysis of arterial thrombi.

PMID- 15254045
TI  - Multi-institutional trial of preoperative chemoradiotherapy in patients with
      potentially resectable gastric carcinoma.
AB  - PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of
      patients with localized gastric carcinoma, and more than 60% die of cancer
      following an R0 resection. A multi-institutional study of preoperative
      chemoradiotherapy was done to assess the R0 resection rate, pathologic complete
      response (pathCR) rate, safety, and survival in patients with resectable gastric
      carcinoma. PATIENTS AND METHODS: Operable patients with localized gastric
      adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic
      ultrasonography (EUS). Patients received up to two 28-day cycles of induction
      chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of
      radiation plus concurrent fluorouracil. Patients were then staged and surgery was
      attempted. RESULTS: Thirty-four patients were registered at three institutions.
      One ineligible patient was excluded. Most patients had a promixal cancer and
      EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0
      resection rate was 70% and pathCR rate was 30%. A pathologic partial response (<
      10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T
      plus N and postsurgery T plus N correlation showed significant downstaging (P =
      <.01). The median survival time for 33 patients was 33.7 months. Patients
      achieving a pathCR or pathPR had a significantly longer median survival time
      (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There
      were two treatment-related deaths. CONCLUSION: Our data suggest that the three
      step strategy of preoperative induction chemotherapy followed by
      chemoradiotherapy resulted in substantial pathologic response that resulted in
      durable survival time. This strategy is worthy of a direct comparison with
      postoperative adjuvant chemoradiotherapy.

PMID- 15254046
TI  - Gene expression alterations in prostate cancer predicting tumor aggression and
      preceding development of malignancy.
AB  - PURPOSE: The incidence of prostate cancer is frequent, occurring in almost one
      third of men older than 45 years. Only a fraction of the cases reach the stages
      displaying clinical significance. Despite the advances in our understanding of
      prostate carcinogenesis and disease progression, our knowledge of this disease is
      still fragmented. Identification of the genes and patterns of gene expression
      will provide a more cohesive picture of prostate cancer biology. PATIENTS AND
      METHODS: In this study, we performed a comprehensive gene expression analysis on
      152 human samples including prostate cancer tissues, prostate tissues adjacent to
      tumor, and organ donor prostate tissues, obtained from men of various ages, using
      the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and
      expression sequence tags). RESULTS: Our results confirm an alteration of gene
      expression in prostate cancer when comparing with nontumor adjacent prostate
      tissues. However, our study also indicates that the gene expression pattern in
      tissues adjacent to cancer is so substantially altered that it resembles a cancer
      field effect. CONCLUSION: We also found that gene expression patterns can be used
      to predict the aggressiveness of prostate cancer using a novel model.

PMID- 15254047
TI  - Allogeneic vaccination with a B7.1 HLA-A gene-modified adenocarcinoma cell line
      in patients with advanced non-small-cell lung cancer.
AB  - PURPOSE: To determine the safety, immunogenicity, and clinical response to an
      allogeneic tumor vaccine for non-small-cell lung cancer, we conducted a phase I
      trial in patients with advanced metastatic disease. PATIENTS AND METHODS: We
      treated 19 patients with a vaccine based on an adenocarcinoma line (AD100)
      transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated
      intradermally with 5 x 10(7) cells once every 2 weeks. Three vaccinations
      represented one course of treatment. If patients had complete response, partial
      response, or stable disease, they continued with the vaccinations for up to three
      courses (nine vaccinations). Immune response was assessed by a change between pre
      study and postvaccination enzyme-linked immunospot frequency of purified CD8 T
      cells secreting interferon-gamma in response to in vitro challenge with AD100.
      RESULTS: Four patients experienced serious adverse events that were unrelated to
      vaccine. Another four patients experienced only minimal skin erythema. All but
      one patient had a measurable CD8 response after three immunizations. The immune
      response of six surviving, clinically responding patients shows that CD8 titers
      continue to be elevated up to 150 weeks, even after cessation of vaccination.
      Overall, one patient had a partial response, and five had stable disease. Median
      survival for all patients is 18 months (90% CI, 7 to 23 months), with
      corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and
      30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not
      bear a significant relation to response. CONCLUSION: Minimal toxicity and good
      survival in this small population suggest clinical benefit from vaccination.

PMID- 15254048
TI  - Autologous dendritic cell vaccines for non-small-cell lung cancer.
AB  - PURPOSE: Therapeutic outcomes of definitively treated non-small-cell lung cancer
      (NSCLC) are unacceptably poor. A wealth of preclinical information, and a modest
      amount of clinical information indicate that dendritic cell (DC) vaccines have
      therapeutic potential. Only a handful of NSCLC patients have been included in DC
      clinical trials. We delivered autologous DC vaccines to 16 individuals with stage
      IA to IIIB NSCLC treated with surgery, chemoradiation, or multimodality therapy.
      The objectives of the study were to evaluate tolerability and measure immunologic
      responses to DC vaccines in a heterogeneous group of NSCLC patients. METHODS: DC
      vaccines were generated from CD14+ precursors, pulsed with apoptotic bodies of an
      allogeneic NSCLC cell line that overexpressed Her2/neu, CEA, WT1, Mage2, and
      survivin. DCs were partially matured with a factor that induced surface molecule
      expression but minimal cytokine production. Individuals were immunized
      intradermally two times, 1 month apart. Peripheral blood was drawn serially over
      16 weeks, and immune responses were measured by interferon-gamma ELISPOT.
      RESULTS: There were no unanticipated or serious adverse events. Immunologic
      responses followed three distinct patterns of reactivity: (1) five of 16 patients
      showed no clear immunologic response, (2) five of 16 patients showed a tumor
      antigen independent response, and (3) six of 16 show an antigen specific
      response. Immunologic responses were independent of stage and prior therapy.
      Favorable and unfavorable clinical outcomes were independent of measured
      immunologic responses. CONCLUSION: Vaccines were well tolerated and had biologic
      activity in a variety of NSCLC patients. Establishing an optimal approach will
      require comparative studies in well-defined NSCLC patient groups.

PMID- 15254049
TI  - Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients
      with acute lymphoblastic leukemia: no difference in related compared with
      unrelated transplant in first complete remission.
AB  - PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute
      lymphoblastic leukemia (ALL) patients is still not clear, and only limited data
      are available from the literature. We analyzed factors affecting clinical outcome
      of ALL patients receiving a related or unrelated stem-cell graft from matched
      donors. PATIENTS AND METHODS: The total study population was 264 adult patients
      receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone
      marrow transplantation centers between 1990 and 2002. Of these, 221 patients
      receiving a matched related or unrelated graft were analyzed. One hundred forty
      eight patients received transplantation in complete remission; 62 patients were
      in relapse; and 11 patients were refractory to chemotherapy before transplant.
      Fifty percent of patients received bone marrow, and 50% received peripheral blood
      stem cell from a human leukocyte antigen-identical related (n = 103), or matched
      unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was
      28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation),
      and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an
      advantage regarding DFS in favor of patients receiving transplantation during
      their first complete remission (CR) in comparison with patients receiving
      transplantation in or after second CR (P =.014) or who relapsed (P <.001). We
      observed a clear trend toward improved survival in favor of B-lineage ALL
      patients compared with T-lineage ALL patients (P =.052), and Philadelphia
      chromosome-positive patients had no poorer outcome than Philadelphia chromosome
      negative patients. Total-body irradiation-based conditioning improved DFS in
      comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or
      matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL
      patients should be performed in first CR.

PMID- 15254050
TI  - Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by
      front-line autotransplantation after complete remission: a cohort study by the
      Groupe d'Etude des Lymphomes de l'Adulte.
AB  - PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma
      (NHL) patients with adverse prognostic factors when autotransplantation (ASCT)
      was performed after complete remission. However, there is no agreement on the
      prognostic factors for patients treated with ASCT. We aimed to estimate the
      prognostic effect of clinical and biologic variables on relapse and survival
      rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients
      treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete
      remission after high-dose cyclophosphamide, doxorubicin, vincristine, and
      prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The
      International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%,
      and 3 for 15%. Univariate and Cox multivariate survival analyses were
      retrospectively performed on this population. RESULTS: Overall survival was 75 +/
      5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these
      scores were 54% and 44%, respectively. The IPI score had no prognostic value and
      only the following parameters adversely affected overall survival and DFS (P
      <.05): marrow involvement; more than one extranodal site; histology
      (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v
      doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can
      prevent relapse in patients with adverse IPI factors. However, patients
      presenting with a nonanaplastic T-cell phenotype, more than one extranodal site,
      or marrow involvement still have a higher risk of relapse. These factors should
      be taken into account when designing post-ASCT maintenance studies.

PMID- 15254051
TI  - Post-treatment change in serum estrone predicts mammographic percent density
      changes in women who received combination estrogen and progestin in the
      Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
AB  - PURPOSE: Postmenopausal estrogen and progestin therapy (EPT) increases
      mammographic percent density and breast cancer risk substantially more than does
      estrogen therapy alone. We determined whether increases in serum estrone as a
      function of treatment predict increases in mammographic percent density. METHODS:
      We measured mammographic percent density and serum estrone levels in participants
      in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly
      assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and
      medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and
      MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per
      28-day cycle. We used linear regression to determine whether serum estrone
      changes predicted mammographic percent density changes from baseline to 1 year.
      RESULTS: Mammographic percent density increased with increasing change in estrone
      level in the EPT groups, but not in the CEE group. Combined, the mammographic
      percent density in the three EPT groups demonstrated an absolute increase of
      2.95% per 100 pg/mL increase in serum estrone level (P =.0003). The absolute
      increases were 4.09% (P =.0018) in the CEE + MPA continuous group, 2.79% (P
      =.0292) in the CEE + MPA cyclical group, and 1.40% (P =.36) in the CEE + MP
      group, but the differences among the EPT groups were not statistically
      significant. CONCLUSION: Greater increase in serum estrone level as a function of
      treatment is a significant predictor of increase in mammographic percent density
      in women randomly assigned to the combination of estrogen and progestin.

PMID- 15254052
TI  - Randomized phase II study of two irinotecan schedules for patients with
      metastatic breast cancer refractory to an anthracycline, a taxane, or both.
AB  - PURPOSE: A pressing need exists for agents active against anthracycline- or
      taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical
      trials suggested that irinotecan might have such activity. We conducted this
      multicenter phase II study to assess efficacy and tolerability of two irinotecan
      schedules. PATIENTS AND METHODS: MBC patients who experienced disease progression
      after one to three chemotherapy regimens, including at least one anthracycline-
      or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles
      comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240
      mg/m(2) every 3 weeks. RESULTS: The weekly arm had 52 assessable patients; the
      every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective
      response (complete regression [CR] + partial regression [PR]) rate was 23% (one
      CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range,
      1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to
      14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine
      PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to
      13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3
      months). Treatment generally was well tolerated, especially in the weekly arm.
      Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%)
      and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%),
      dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.
      CONCLUSION: Irinotecan is active with good tolerability in refractory MBC.
      Irinotecan (especially weekly) warrants additional study as monotherapy and in
      combination regimens in this setting.

PMID- 15254053
TI  - Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase
      ii trial of concurrent radiation and chemotherapy for advanced squamous cell
      carcinomas of the head and neck.
AB  - PURPOSE: To define further the role of concurrent chemoradiotherapy for patients
      with advanced squamous carcinoma of the head and neck. PATIENTS AND METHODS: The
      Radiation Therapy Oncology Group developed this three-arm randomized phase II
      trial. Patients with stage III or IV squamous carcinoma of the oral cavity,
      oropharynx, or hypopharynx were eligible. Each of three arms proposed a radiation
      schedule of 70 Gy in 35 fractions. Patients on arm 1 were to receive cisplatin 10
      mg/m(2) daily and fluorouracil (FU) 400 mg/m(2) continuous infusion (CI) daily
      for the final 10 days of treatment. Treatment on arm 2 consisted of hydroxyurea 1
      g every 12 hours and FU 800 mg/m(2)/d CI delivered with each fraction of
      radiation. Arm 3 patients were to receive weekly paclitaxel 30 mg/m(2) and
      cisplatin 20 mg/m(2). Patients randomly assigned to arms 1 and 3 were to receive
      their treatments every week; patients on arm 2 were to receive their therapy
      every other week. RESULTS: Between 1997 and 1999, 241 patients were entered onto
      study; 231 were analyzable. Ninety-two percent, 79%, and 83% of patients on arms
      1, 2, and 3, respectively, were able to complete their radiation as planned or
      with an acceptable variation. Fewer than 10% of patients had unacceptable
      deviations or incomplete chemotherapy in the three arms. Estimated 2-year disease
      free and overall survival rates were 38.2% and 57.4% for arm 1, 48.6% and 69.4%
      for arm 2, and 51.3% and 66.6% for arm 3. CONCLUSION: We have demonstrated that
      three different approaches of concurrent multiagent chemotherapy and radiation
      were feasible and could be delivered to patients in a multi-institutional setting
      with high compliance rates.

PMID- 15254054
TI  - Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in
      the Metropolitan Detroit Cancer Surveillance System.
AB  - PURPOSE: Population-based estimates of the incidence of brain metastases are not
      generally available. The purpose of this study was to calculate population-based
      incidence proportions (IPs) of brain metastases from single primary lung,
      melanoma, breast, renal, or colorectal cancer. PATIENTS AND METHODS: Patients
      diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer
      (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS)
      were used for analysis. IP of brain metastases by primary site and variable of
      interest (race, sex, age at diagnosis of primary cancer, and Surveillance,
      Epidemiology, and End Results [SEER] stage of primary cancer) was calculated with
      95% CIs. RESULTS: Total IP percentage (IP%) of brain metastases was 9.6% for all
      primary sites combined, and highest for lung (19.9%), followed by melanoma
      (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial
      differences were seen with African Americans demonstrating higher IP% of brain
      metastases compared with other racial groups for most primary sites. IP% was
      significantly higher for female patients with lung cancer, and significantly
      higher for male patients with melanoma. The highest IP% of brain metastases
      occurred at different ages at diagnoses: age 40 to 49 years for primary lung
      cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers;
      and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER
      stage of primary cancer advanced for all primary sites. CONCLUSION: Total IP% of
      brain metastases was lower than previously reported, and it varied by primary
      site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary
      cancer.

PMID- 15254055
TI  - Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of
      bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer
      Group and Pediatric Oncology Group study.
AB  - PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive
      neuroectodermal tumor (PNET) of bone were entered onto a randomized trial
      evaluating whether the addition of ifosfamide and etoposide to vincristine,
      doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS:
      Thirty-two patients had metastases to lungs only, 12 patients had metastases to
      bone marrow or bones only, 64 patients had metastases in multiple sites, and five
      patients had metastases in other sites; seven patients could not be assessed
      precisely. Treatment comprised 9 weeks of chemotherapy before local control and
      42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2
      mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or
      dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3
      weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for
      5 days. RESULTS: Patients treated on regimen B did not have significantly better
      survival than those treated on regimen A. The event-free survival (EFS) and
      survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for
      those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for
      those treated on regimen B. Patients who had only lung metastases had EFS and S
      of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic
      deaths (5%), four from cardiac toxicity and two from sepsis (four treated on
      regimen B and two treated on regimen A). Two had second malignant neoplasms.
      CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve
      outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at
      diagnosis.

PMID- 15254056
TI  - Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in
      children enrolled in a registry.
AB  - PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare
      and aggressive tumor of early childhood. The poor outcome with conventional
      infant brain tumor therapy has resulted in a lack of clear treatment guidelines.
      A registry has been established to create an outcomes database and to facilitate
      biology studies for this tumor. MATERIALS AND METHODS: A standardized data sheet
      was provided to treating physicians listing the reports that were to be sent to
      the registry for abstraction. Follow-up information was sought twice yearly.
      RESULTS: Information was complete for 42 patients. Median age at diagnosis was 24
      months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors
      were infratentorial; 26 were supratentorial. Twenty patients (48%) received a
      primary complete resection. Primary therapy included chemotherapy in all
      patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients
      (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or
      progressive disease was reported in nine and 19 patients, respectively. Twenty
      seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one
      patient died of toxicity. Fourteen patients (33%) show no evidence of disease
      (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the
      median event-free survival is 10 months. CONCLUSION: Aggressive therapy has
      prolonged the natural history in a subset of children. Prospective multi
      institutional and national clinical trials designed specifically for AT/RT are
      needed. Enrollment onto the AT/RT registry should be continued.

PMID- 15254057
TI  - Treatment of relapsed Wilms' tumor with high-dose therapy and autologous
      hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital.
AB  - PURPOSE: To investigate whether high-dose therapy with hematopoietic stem-cell
      rescue (HSCR) will improve survival for patients with relapsed Wilms' tumor.
      PATIENTS AND METHODS: Thirteen children with relapsed Wilms' tumor were treated
      with one or two cycles of high-dose chemotherapy (HDT) followed by autologous
      HSCR. Twelve of 13 patients received reinduction chemotherapy before HDT and
      HSCR. The median age at diagnosis was 4.8 years, and the median time to relapse
      was 12 months. The histology was favorable in 12 of 13 patients. The ablative
      regimens included: (1) thiotepa (TT)/cyclophosphamide (CTX)/carboplatin (CP; n =
      2); (2) TT/CTX (n = 5); (3) TT/etoposide (ETP; n = 1); and (4) CP/ETP/CTX (n =
      1). Four patients received two cycles of HDT and HSCR. Cycle 1 consisted of
      CP/ETP/CTX, and melphalan/CTX were used in cycle 2. RESULTS: Seven of 13 patients
      are alive without evidence of disease, with a median follow-up of 30 months. The
      4-year estimated event-free survival (EFS) rate is 60% (95% CI, 0.40 to 6.88),
      and the overall survival (OS) at 4 years is 73% (95% CI, 0.40 to 6.86). There was
      no transplant-related mortality. All patients engrafted to an absolute neutrophil
      count 500/microL at a median of 13 days (range, 8 to 62 days) and had an
      unsustained platelet count > 20.0 micro at a median of 16 days (range, 10 to 202
      days). CONCLUSION: Our results suggest that HDT with HSCR is an effective
      treatment for patients with Wilms' tumor who experience relapse.

PMID- 15254058
TI  - Clinical and immunologic effects of subcutaneously administered interleukin-12
      and interferon alfa-2b: phase I trial of patients with metastatic renal cell
      carcinoma or malignant melanoma.
AB  - PURPOSE: Interleukin-12 (IL-12) and interferon alfa-2b (IFN-alpha-2b) are
      pleiotropic cytokines with activity in renal cell carcinoma (RCC) and malignant
      melanoma (MM) as single agents. Preclinical studies suggest concurrent
      administration may have synergistic antitumor effects. We conducted a phase I
      trial of concurrent subcutaneous (SC) administration of IL-12 and IFN-alpha-2b in
      patients with metastatic RCC or MM to determine toxicity, maximum-tolerated dose,
      preliminary efficacy, and effects on chemokine/cytokine gene expression in
      peripheral blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Cohorts of
      three to six patients were treated with escalating doses of IL-12 (dose I, 100
      ng/kg; dose II, 300 ng/kg; dose III, 500 ng/kg; dose IV, 500 ng/kg SC) given
      twice weekly and IFN-alpha-2b (dose I, 1.0 MU/m(2); dose II, 1.0 MU/m(2); dose
      III, 1.0 MU/m(2); dose IV, 3.0 MU/m(2) SC) three times weekly in 4-week cycles.
      Effects on gene expression were assessed by reverse transcriptase polymerase
      chain reaction. RESULTS: Twenty-six patients (19 with RCC, seven with MM) were
      accrued at dose levels I (n = 3), II (n = 3), III (n = 13), and IV (n = 7). Dose
      limiting toxicity included grades 3 and 4 hepatotoxicity and
      neutropenia/leukopenia. Patients received a median of three cycles of treatment.
      Two patients with RCC and one patient with MM had partial responses. Median
      survival was 13.8 months. Reverse transcriptase polymerase chain reaction on
      PBMCs revealed induction of IP-10, Mig, B7.1 (CD80), interleukin-5, and
      interferon gamma in selected patients. CONCLUSION: Concurrent SC administration
      of IL-12 and IFN-alpha-2b is possible at the dose levels utilized. Recommended
      doses for phase II trials are 500 ng/kg IL-12 and 1.0 MU/m(2) IFN-alpha-2b.
      Consistent induction of IP-10 and Mig, as well as variable induction of B7.1,
      interleukin-5, and interferon gamma expression was noted in PBMCs.

PMID- 15254059
TI  - Comparison of pharmacokinetics and pharmacodynamics of docetaxel and Cisplatin in
      elderly and non-elderly patients: why is toxicity increased in elderly patients?
AB  - PURPOSE: Following phase I studies of docetaxel and cisplatin in patients with
      non-small-cell lung cancer, the recommended doses of docetaxel were different for
      elderly (> or = 75 years) and non-elderly (< 75 years) patients. To elucidate the
      mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were
      investigated in two phase II studies separately conducted in elderly and non
      elderly patients. PATIENTS AND METHODS: Twenty-seven elderly and 25 non-elderly
      patients were treated with three weekly administrations of docetaxel and
      cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m(2) for elderly
      and non-elderly patients, respectively. All patients received 25 mg/m(2) of
      cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin
      were compared in elderly and non-elderly patients. RESULTS: There were no
      differences in pharmacokinetics of docetaxel or cisplatin between elderly versus
      non-elderly patients with regard to clearance and volume of distribution. In the
      pharmacodynamic analysis, neutropenia was positively correlated with the area
      under the concentration-time curve for docetaxel but not for cisplatin. In
      evaluating the relationship between neutropenia and the area under the
      concentration-time curve of docetaxel, elderly patients experienced greater
      neutropenia than those predicted by a pharmacodynamic model developed in non
      elderly patients; the residual for prediction of the percent change in neutrophil
      count was -11.2% (95% CI, -21.8 to -0.5%). CONCLUSION: The pharmacokinetics of
      docetaxel and unchanged cisplatin were not different between elderly and non
      elderly patients. The elderly patients were more sensitive to docetaxel exposure
      than the non-elderly patients, resulting in the different recommended doses for
      the phase II studies.

PMID- 15254060
TI  - Gabapentin for neuropathic cancer pain: a randomized controlled trial from the
      Gabapentin Cancer Pain Study Group.
AB  - PURPOSE: To determine the analgesic effect of the addition of gabapentin to
      opioids in the management of neuropathic cancer pain. PATIENTS AND METHODS: One
      hundred twenty-one consecutive patients with neuropathic pain due to cancer,
      partially controlled with systemic opioids, participated in a multicenter,
      randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from
      August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in
      addition to stable opioid dose. Extra opioid doses were available as needed. Zero
      to 10 numerical scale was used to rate average daily pain. The average pain score
      over the whole follow-up period was used as main outcome measure. Secondary
      outcome measures were: intensity of burning pain, shooting/lancinating pain,
      dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes
      of lancinating pain, presence of allodynia, and daily extra doses of opioid
      analgesics. RESULTS: Overall, 79 patients received gabapentin and 58 (73%)
      completed the study; 41 patients received placebo and 31 (76%) completed the
      study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a
      significant difference of average pain intensity between gabapentin (pain score,
      4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome
      measures, dysesthesia score showed a statistically significant difference (P
      =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at
      least 3 days of pain assessments). Reasons for withdrawing patients from the
      trial were adverse events in six patients (7.6%) receiving gabapentin and in
      three patients receiving placebo (7.3%). CONCLUSION: Gabapentin is effective in
      improving analgesia in patients with neuropathic cancer pain already treated with
      opioids.

PMID- 15254061
TI  - Recommended guidelines for the treatment of cancer treatment-induced diarrhea.
AB  - PURPOSE: To update and expand on previously published clinical practice
      guidelines for the treatment of cancer treatment-induced diarrhea. METHODS: An
      expert multidisciplinary panel was convened to review the recent literature and
      discuss recommendations for updating the practice guidelines previously published
      by this group in the Journal of Clinical Oncology in 1998. MEDLINE searches were
      performed and the relevant literature published since 1998 was reviewed by all
      panel members. The treatment recommendations and algorithm were revised by panel
      consensus. RESULTS: A recent review of early toxic deaths occurring in two
      National Cancer Institute-sponsored cooperative group trials of irinotecan plus
      high-dose fluorouracil and leucovorin for advanced colorectal cancer has led to
      the recognition of a life-threatening gastrointestinal syndrome and highlighted
      the need for vigilant monitoring and aggressive therapy for this serious
      complication. Loperamide remains the standard therapy for uncomplicated cases.
      However, the revised guidelines reflect the need for recognition of the early
      warning signs of complicated cases of diarrhea and the need for early and
      aggressive management, including the addition of antibiotics. Management of
      radiation-induced diarrhea is similar but may not require hospitalization, and
      chronic low- to intermediate-grade symptoms can be managed with continued
      loperamide. CONCLUSION: With vigilant monitoring and aggressive therapy for
      cancer treatment-induced diarrhea, particularly in patients with early warning
      signs of severe complications, morbidity and mortality may be reduced.

PMID- 15254062
TI  - Bone imaging in metastatic breast cancer.
AB  - Bone is the most common site to which breast cancer metastasizes. Imaging-by
      skeletal scintigraphy, plain radiography, computed tomography, or magnetic
      resonance imaging-is an essential part, and positron emission tomography or
      single-photon emission computed tomography have a potential of evaluating bone
      metastases, but no consensus exists as to the best modality for diagnosing the
      lesion and for assessing its response to treatment. Imaging bone metastases is
      problematic because the lesions can be osteolytic, osteoblastic, or mixed, and
      imaging modalities are based on either direct anatomic visualization of the bone
      or tumor or indirect measurements of bone or tumor metabolism. Although bone
      metastases can be treated, their response to treatment is considered
      "unmeasurable" according to existing response criteria. Therefore, the process by
      which oncologists and radiologists diagnose and monitor the response of bone
      metastases needs revision, and the current inability to assess the response of
      bone metastases excludes patients with breast cancer and bone disease from
      participating in clinical trials of new treatments for breast cancer. In this
      review of the MEDLINE literature, we discuss the pros and cons of each modality
      for diagnosing bone metastases and for assessing their response to treatment and
      we present a practical approach for diagnosis and assessment of bone metastasis.

PMID- 15254063
TI  - The biology and clinical relevance of the PTEN tumor suppressor pathway.
AB  - Genetic alterations targeting the PTEN tumor suppressor gene are among the most
      frequently noted somatic mutations in human cancers. Such lesions have been noted
      in cancers of the prostate and endometrium and in glioblastoma multiforme, among
      many others. Moreover, germline mutation of PTEN leads to the development of the
      related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan
      Zonana syndrome, wherein breast and thyroid cancer incidence is elevated. The
      protein product, PTEN, is a lipid phosphatase, the enzymatic activity of which
      primarily serves to remove phosphate groups from key intracellular
      phosphoinositide signaling molecules. This activity normally serves to restrict
      growth and survival signals by limiting activity of the phosphoinositide-3 kinase
      (PI3K) pathway. Multiple lines of evidence support the notion that this function
      is critical to the ability of PTEN to maintain cell homeostasis. Indeed, the
      absence of functional PTEN in cancer cells leads to constitutive activation of
      downstream components of the PI3K pathway including the Akt and mTOR kinases. In
      model organisms, inactivation of these kinases can reverse the effects of PTEN
      loss. These data raise the possibility that drugs targeting these kinases, or
      PI3K itself, might have significant therapeutic activity in PTEN-null cancers.
      Akt kinase inhibitors are still in development; however, as a first test of this
      hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin
      and rapamycin analogs are underway.

PMID- 15254064
TI  - Value of positron emission tomography scan in staging cancers, and an unusual
      presentation of acute myeloid leukemia. Case 1. Demonstration of CNS lymphoma by
      positron emission tomography scan affects management.

PMID- 15254065
TI  - Value of positron emission tomography scan in staging cancers, and an unusual
      presentation of acute myeloid leukemia. Case 2. Detection of an appendiceal
      carcinoma by whole-body positron emission tomography after Caesarean section.

PMID- 15254066
TI  - Value of positron emission tomography scan in staging cancers, and an unusual
      presentation of acute myeloid leukemia. Case 3. Acute myeloid leukemia presenting
      with lytic bone lesions.

PMID- 15254067
TI  - A recent illustration of some essentials of circadian chronotherapy study design.

PMID- 15254070
TI  - Thematic review series: brain Lipids. Cholesterol metabolism in the central
      nervous system during early development and in the mature animal.
AB  - Unesterified cholesterol is an essential structural component of the plasma
      membrane of every cell. During evolution, this membrane came to play an
      additional, highly specialized role in the central nervous system (CNS) as the
      major architectural component of compact myelin. As a consequence, in the human
      the mean concentration of unesterified cholesterol in the CNS is higher than in
      any other tissue (approximately 23 mg/g). Furthermore, even though the CNS
      accounts for only 2.1% of body weight, it contains 23% of the sterol present in
      the whole body pool. In all animals, most growth and differentiation of the CNS
      occurs in the first few weeks or years after birth, and the cholesterol required
      for this growth apparently comes exclusively from de novo synthesis. Currently,
      there is no evidence for the net transfer of sterol from the blood into the brain
      or spinal cord. In adults, the rate of synthesis exceeds the need for new
      structural sterol, so that net movement of cholesterol out of the CNS must take
      place. At least two pathways are used for this excretory process, one of which
      involves the formation of 24(S)-hydroxycholesterol. Whether or not changes in the
      plasma cholesterol concentration alter sterol metabolism in the CNS or whether
      such changes affect cognitive function in the brain or the incidence of dementia
      remain uncertain at this time.

PMID- 15254071
TI  - Contribution of muscle afferents to prolonged flexion withdrawal reflexes in
      human spinal cord injury.
AB  - The contribution of force-sensitive muscular afferents to prolonged flexion
      withdrawal reflexes, or flexor spasms, after human spinal cord injury (SCI) was
      investigated. In three separate experimental conditions, flexion reflexes were
      triggered in subjects with SCI using trains of electrocutaneous stimuli delivered
      at the foot and lower leg and compared with reflexes elicited via intramuscular
      (i.m.) electrical stimuli. In the first experiment, flexion reflexes were
      elicited using i.m. stimuli to the tibialis anterior (TA) in the majority of
      subjects tested. The ratio of peak isometric ankle to hip torques during i.m.
      triggered reflexes were proportionally similar to those evoked by
      electrocutaneous foot or shank stimulation, although the latency to onset and
      peak flexion torques were significantly longer with i.m. stimulation. In the
      second experiments, the amplitude and frequency of i.m. TA stimulation were
      varied to alter the stimulus-induced muscle torque. Peak ankle and hip torques
      generated during the flexion reflex responses were correlated to a greater extent
      with stimulus-induced muscle torques as compared with the modulated stimulus
      parameters. In the third experimental series, i.m. stimuli delivered to the
      gastrocnemius (GS) elicited flexion reflexes in approximately half of the
      subjects tested. The combined data indicate a potentially prominent role of the
      stimulus-induced muscle contraction to the magnitude and latency of flexor reflex
      behaviors after i.m. TA stimulation. Results after i.m. GS stimulation indicate
      multi-joint flexion reflexes can also be elicited, although to a lesser extent
      than i.m. TA stimulation.

PMID- 15254072
TI  - Enhanced excitability compensates for high-pressure-induced depression of
      cortical inputs to the hippocampus.
AB  - High pressure (>1.0 MPa) induces the high-pressure neurological syndrome (HPNS)
      characterized by increased excitability of the CNS and cognitive impairments
      involving memory disorders. The perforant-path transfer of cortical information
      to the hippocampal formation is important for memory acquisition. High pressure
      may alter information transfer in this connection. We used rat corticohippocampal
      slices for studying the effect of pressure on the transfer function between
      synaptic inputs from the medial perforant path (MPP) and spike generation by
      granule cells (GC) of the dentate gyrus. High pressure (10.1 MPa) reduced single
      MPP field excitatory postsynaptic potential (fEPSP) amplitude and slope by nearly
      50%. Field antidromic action potentials (AAPs) elicited by stimulation of GC
      axons, and population spike (PS) generation by the pressure-depressed MPP fEPSP
      were not significantly altered at hyperbaric conditions. Nevertheless the
      relationship PS/fEPSP increased at high pressure, indicating dendritic
      hyperexcitability in the GC. PSs elicited by paired-pulse MPP fEPSPs at 10- to
      200-ms interstimulus intervals and PS generated by trains of five fEPSPs at 25 Hz
      were also not affected in spite of severe pressure-induced synaptic depression.
      Similarly, trains of AAPs at 25-50 Hz were not significantly changed. Trains of
      fEPSPs at higher frequency (50 Hz), however, induced additional spikes at high
      pressure, indicating pressure disruption of the regular low-pass filter
      properties of the DG. Such effect was closely mimicked by partial blockade of
      GABAA inhibition. High pressure depresses synaptic activity while increases
      excitability in the neuronal dendrites but not in the axons. This mechanism,
      allowing neuronal communication at low input signals, may partially cope with
      pressure effects at the low frequency range (<25 Hz) but losses reliability at
      higher frequencies (>50 Hz).

PMID- 15254074
TI  - Effect of subthreshold up and down states on the whisker-evoked response in
      somatosensory cortex.
AB  - Changes in spontaneous activity within the cortex recognized by subthreshold
      fluctuations of the membrane potential of cortical neurons modified the response
      of cortical neurons to sensory stimuli. Sensory stimuli occurring in the
      hyperpolarized "down" state evoked a larger depolarization and were more
      effective in evoking action potentials than stimuli occurring in the depolarized
      "up" state. Direct electrical stimulation of the thalamus showed the same
      dependence on the cell's state at the time of the stimulus, ruling out a strictly
      thalamic mechanism. Stimuli were more effective at triggering action potentials
      in the down state even during moderate de- or hyperpolarization of the somatic
      membrane potential. The postsynaptic potential (PSP) evoked from the down state
      was larger than the up state PSP but achieved about the same peak membrane
      potential, which was also near the reversal potential of the PSP (about -51 mV).
      Chloride loading shifted the reversal potentials of both the up state and the
      whisker-evoked PSP toward a more depolarized membrane potential. In addition, the
      threshold for action potentials evoked from the down state was lower than for
      spikes evoked in the up state. Thus the larger PSP from the down state may be
      caused by its larger driving force, and the state dependence of action potential
      generation in response to whisker stimulation may in part be related to a shift
      in threshold. Different mechanisms are therefore responsible for the state
      dependence of PSP amplitude and the spike frequency response to the whisker
      stimulus.

PMID- 15254073
TI  - Presynaptic GABAB receptors modulate thalamic excitation of inhibitory and
      excitatory neurons in the mouse barrel cortex.
AB  - Cortical inhibition plays an important role in the processing of sensory
      information, and the enlargement of receptive fields by the in vivo application
      of GABAB receptor antagonists indicates that GABAB receptors mediate some of this
      cortical inhibition. Although there is evidence of postsynaptic GABAB receptors
      on cortical neurons, there is no evidence of GABAB receptors on thalamocortical
      terminals. Therefore to determine if presynaptic GABAB receptors modulate the
      thalamic excitation of layer IV inhibitory neurons and excitatory neurons in
      layers II-III and IV of the somatosensory "barrel" cortex of mice, we used a
      thalamocortical slice preparation and patch-clamp electrophysiology. Stimulation
      of the ventrobasal thalamus elicited excitatory postsynaptic currents (EPSCs) in
      cortical neurons. Bath application of baclofen, a selective GABAB receptor
      agonist, reversibly decreased AMPA receptor-mediated and N-methyl-D-aspartate
      (NMDA) receptor-mediated EPSCs in inhibitory and excitatory neurons. The GABAB
      receptor antagonist, CGP 35348, reversed the inhibition produced by baclofen.
      Blocking the postsynaptic GABAB receptor-mediated effects with a Cs+ -based
      recording solution did not affect the inhibition, suggesting a presynaptic effect
      of baclofen. Baclofen reversibly increased the paired-pulse ratio and the
      coefficient of variation, consistent with the presynaptic inhibition of glutamate
      release. Our results indicate that the presynaptic activation of GABAB receptors
      modulates thalamocortical excitation of inhibitory and excitatory neurons and
      provide another mechanism by which cortical inhibition can modulate the
      processing of sensory information.

PMID- 15254075
TI  - Preparatory activity in visual cortex indexes distractor suppression during
      covert spatial orienting.
AB  - The deployment of spatial attention induces retinotopically specific increases in
      neural activity that occur even before a target stimulus is presented. Although
      this preparatory activity is thought to prime the attended regions, thereby
      improving perception and recognition, it is not yet clear whether this activity
      is a manifestation of signal enhancement at the attended locations or suppression
      of interference from distracting stimuli (or both). We investigated the
      functional role of these preparatory shifts by isolating a distractor suppression
      component of selection. Behavioral data have shown that manipulating the
      probability that visual distractors will appear modulates distractor suppression
      without concurrent changes in signal enhancement. In 2 experiments, functional
      magnetic resonance imaging revealed increased cue-evoked activity in
      retinotopically specific regions of visual cortex when increased distractor
      suppression was elicited by a high probability of distractors. This finding
      directly links cue-evoked preparatory activity in visual cortex with a distractor
      suppression component of visual selective attention.

PMID- 15254076
TI  - Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and
      electrophysiologically heterogeneous.
AB  - The dorsal raphe nucleus (DRN) projects serotonergic axons throughout the brain
      and is involved in a variety of physiological functions. However, it also
      includes a large population of cells that contain other neurotransmitters. To
      clarify the physiological and pharmacological differences between the
      serotonergic and nonserotonergic neurons of the DRN, their postsynaptic responses
      to 5-hydroxytryptamine (5-HT, serotonin) and to selective activation of 5-HT1A or
      5-HT2A/C receptors and their action potential characteristics were determined
      using in vitro patch-clamp recordings. The slices containing these neurons were
      then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic
      neurons. It was found that subpopulations of both serotonergic and
      nonserotonergic neurons responded to 5-HT with outward (i.e., inhibitory) and
      inward (i.e., excitatory) currents, responded to both 5-HT1A and 5-HT2A/C
      receptor activation with outward and inward currents, respectively, and displayed
      overlapping action potential characteristics. These findings suggest that
      serotonergic and nonserotonergic neurons in the DRN are both heterogeneous with
      respect to their individual pharmacological and electrophysiological
      characteristics. The findings also suggest that the activity of the different
      populations of DRN neurons will display heterogeneous changes when the
      serotonergic tone in the DRN is altered by neurological disorders or by drug
      treatment.

PMID- 15254077
TI  - Functional impact of alternative splicing of human T-type Cav3.3 calcium
      channels.
AB  - Low-voltage-activated T-type (Cav3) Ca2+ channels produce low-threshold spikes
      that trigger burst firing in many neurons. The CACNA1I gene encodes the Cav3.3
      isoform, which activates and inactivates much more slowly than the other Cav3
      channels. These distinctive kinetic features, along with its brain-region
      specific expression, suggest that Cav3.3 channels endow neurons with the ability
      to generate long-lasting bursts of firing. The human CACNA1I gene contains two
      regions of alternative splicing: variable inclusion of exon 9 and an alternative
      acceptor site within exon 33, which leads to deletion of 13 amino acids
      (Delta33). The goal of this study is to determine the functional consequences of
      these variations in the full-length channel. The cDNA encoding these regions were
      cloned using RT-PCR from human brain, and currents were recorded by whole cell
      patch clamp. Introduction of the Delta33 deletion slowed the rate of channel
      opening. Addition of exon 9 had little effect on kinetics, whereas its addition
      to Delta33 channels unexpectedly slowed both activation and inactivation
      kinetics. Modeling of neuronal firing showed that exon 9 or Delta33 alone reduced
      burst firing, whereas the combination enhanced firing. The major conclusions of
      this study are that the intracellular regions after repeats I and IV play a role
      in channel gating, that their effects are interdependent, suggesting a direct
      interaction, and that splice variation of Cav3.3 channels provides a mechanism
      for fine-tuning the latency and duration of low-threshold spikes.

PMID- 15254078
TI  - Functional organization of visual cortex in the owl monkey.
AB  - In this study, we compared the organization of orientation preference in visual
      areas V1, V2, and V3. Within these visual areas, we also quantified the
      relationship between orientation preference and cytochrome oxidase (CO) staining
      patterns. V1 maps of orientation preference contained both pinwheels and linear
      zones. The location of CO blobs did not relate in a systematic way to maps of
      orientation; although, as in other primates, there were approximately twice as
      many pinwheels as CO blobs. V2 contained bands of high and low orientation
      selectivity. The bands of high orientation selectivity were organized into
      pinwheels and linear zones, but iso-orientation domains were twice as large as
      those in V1. Quantitative comparisons between bands containing high or low
      orientation selectivity and CO dark and light bands suggested that at least four
      functional compartments exist in V2, CO dense bands with either high or low
      orientation selectivity, and CO light bands with either high or low selectivity.
      We also demonstrated that two functional compartments exist in V3, with zones of
      high orientation selectivity corresponding to CO dense areas and zones of low
      orientation selectivity corresponding to CO pale areas. Together with previous
      findings, these results suggest that the modular organization of V1 is similar
      across primates and indeed across most mammals. V2 organization in owl monkeys
      also appears similar to that of other simians but different from that of
      prosimians and other mammals. Finally, V3 of owl monkeys shows a compartmental
      organization for orientation selectivity that remains to be demonstrated in other
      primates.

PMID- 15254079
TI  - Src family kinases are involved in EphA receptor-mediated retinal axon guidance.
AB  - EphA receptor tyrosine kinases and their ephrin ligands play important roles in
      wiring of the developing nervous system. We have investigated here the function
      of Src family kinases (SFKs) in the retinotectal projection to dissect the
      signaling pathways by which EphA receptors control actin/microtubule
      rearrangements that underlie growth cone guidance and collapse. Both EphAs and
      SFKs are expressed broadly in retinal growth cones, and SFKs are recruited to
      EphA receptors after ephrinA stimulation. In the stripe and growth cone collapse
      assays we observe an abolition of EphA-mediated repulsion after inhibiting SFKs,
      either pharmacologically or enzymatically via electroporation-mediated
      overexpression of the SFK inhibitor Csk. In addition, we identify cortactin and
      the RhoGEF ephexin, which interact with EphA receptors in retinal axons, as
      targets of SFK-dependent tyrosine phosphorylation. In sum, our data suggest an
      important role of SFKs as downstream signaling molecules in EphA receptor
      mediated repulsive axon guidance.

PMID- 15254080
TI  - Independent coding of reward magnitude and valence in the human brain.
AB  - Previous research has shown that two components of the event-related brain
      potential, the P300 and feedback negativity, are sensitive to information about
      rewards and penalties. The present study investigated the properties of these
      components in a simple gambling game that required participants to choose between
      cards that were unpredictably associated with monetary gains and losses of
      variable magnitude. The aim was to determine the sensitivity of each component to
      two critical features of reward stimuli: magnitude (small or large) and valence
      (win or loss). A double dissociation was observed, with the P300 sensitive to
      reward magnitude but insensitive to reward valence and the feedback negativity
      showing the opposite pattern, suggesting that these two fundamental features of
      rewarding stimuli are evaluated rapidly and separately in the human brain.
      Subsequent analyses provided additional evidence of functional dissociations
      between the feedback negativity and P300. First, the P300 (but not the feedback
      negativity) showed sensitivity to the reward value of alternative, nonselected
      stimuli. Second, individual differences in the amplitude of the feedback
      negativity correlated with individual differences in risk-taking behavior
      observed after monetary losses, whereas individual differences in P300 amplitude
      were related to behavioral adjustments observed in response to alternative,
      unchosen outcomes.

PMID- 15254081
TI  - Identification and localization of an arachidonic acid-sensitive potassium
      channel in the cochlea.
AB  - Receptor cells of the auditory and vestibular end organs of vertebrates acquire
      various types of potassium channels during development. Their expression and
      kinetics can differ along the tonotopic axis as well as in different cell types
      of the sensory epithelium. These variations can play a crucial role in modulating
      sensory transduction and cochlear tuning. Whole-cell tight-seal recordings of
      isolated hair cells revealed the presence of an arachidonic acid-sensitive A-type
      channel in the short (outer) hair cells of the chicken cochlea. This
      polyunsaturated fatty acid blocked the A-current, thereby increasing the
      amplitude and duration of the voltage response in these cells. We identified the
      gene encoding this channel as belonging to a member of the Shal subfamily, Kv4.2.
      Expression of the recombinant channel shows half-activation and inactivation
      potentials shifted to more positive values relative to native channels,
      suggesting that the native channel is coexpressed with an accessory subunit. RT
      PCR revealed that transcription begins early in development, whereas in situ
      hybridization showed mRNA expression limited to the intermediate and short hair
      cells located in specific regions of the adult cochlea. Additional localization,
      using immunofluorescent staining, revealed clustering in apical-lateral regions
      of the receptor cell as well as in the cochlear ganglion. These experiments
      provide evidence that in addition to membrane proteins modulating excitation in
      these receptor cells, fatty acids contribute to the coding of auditory stimuli
      via these channels.

PMID- 15254082
TI  - An attenuated immune response is sufficient to enhance cognition in an
      Alzheimer's disease mouse model immunized with amyloid-beta derivatives.
AB  - Immunization with amyloid-beta (Abeta) 1-42 has been shown to reduce amyloid
      burden and improve cognition in Alzheimer's disease (AD) model mice. In a human
      trial, possible cognitive benefit was found but in association with significant
      toxicity in a minority of patients. We proposed that immunization with
      nonfibrillogenic Abeta derivatives is much less likely to produce toxicity and
      have previously shown that one such derivative (K6Abeta1-30) can reduce amyloid
      burden in mice to a similar extent as Abeta1-42. Here, we immunized AD model mice
      (Tg2576) with Abeta1-30[E18E19] or with K6Abeta1-30[E18E19]. These peptides were
      designed to be nontoxic and to produce less T-cell response, which has been
      linked to toxicity. K6Abeta1-30[E18E19] induced primarily an IgM response,
      whereas Abeta1-30[E18E19] induced an IgG titer that was lower than previously
      seen with K6Abeta1-30 or Abeta1-42. However, both treated animal groups performed
      better than Tg controls in the radial arm maze. Amyloid burden was similar in
      Abeta1-30[E18E19]-vaccinated mice and their Tg controls, whereas the number of
      medium and small sized plaques was reduced (29-34%) in K6Abeta1-30[E18E19]
      immunized mice compared with Tg controls. Amyloid burden in these mice correlated
      inversely with plasma IgM levels. The cognitive benefit and amyloid reduction in
      the K6Abeta1-30[E18E19]-vaccinated mice are likely to be related to peripheral
      clearance of Abeta, because IgM does not cross the blood-brain barrier because of
      its large size. Our results indicate that these nontoxic Abeta derivatives
      produce an attenuated antibody response, which is less likely to be associated
      with negative side effects while having cognitive benefits.

PMID- 15254083
TI  - Temporal dynamics of neural adaptation effect in the human visual ventral stream.
AB  - When the same visual stimulus is repeatedly presented with a brief interval, the
      brain responses to that stimulus are attenuated relative to those at first
      presentation [neural adaptation (NA)]. Although this effect has been widely
      observed in various regions of human brain, its temporal dynamics as a neuronal
      population has been mostly unclear. In the present study, we used a
      magnetoencephalography (MEG) and conducted a macrolevel investigation of the
      temporal profiles of the NA occurring in the human visual ventral stream. The
      combination of MEG with our previous random dot blinking method isolated the
      neural responses in the higher visual cortex relating to shape perception. We
      dissociated three dimensions of the NA: activation strength, peak latency, and
      temporal duration of neural response. The results revealed that visual responses
      to the repeated compared with novel stimulus showed a significant reduction in
      both activation strength and peak latency but not in the duration of neural
      processing. Furthermore, this acceleration of peak latency showed a significant
      correlation with reaction time of the subjects, whereas no correlation was found
      between the reaction time and the temporal duration of neural responses. These
      results indicate that (1) the NA involves the brain response changes in the
      temporal domain as well as the response attenuation reported previously, and (2)
      this temporal change is primarily observed as a rapid rising of "what" responses,
      rather than a temporal shortening of neural response curves within the visual
      ventral stream as considered previously.

PMID- 15254084
TI  - Behavioral state instability in orexin knock-out mice.
AB  - Narcolepsy is caused by a lack of orexin (hypocretin), but the physiologic
      process that underlies the sleepiness of narcolepsy is unknown. Using orexin
      knock-out (KO) mice as a model of narcolepsy, we critically tested the three
      leading hypotheses: poor circadian control of sleep and wakefulness, inadequate
      activation of arousal regions, or abnormal sleep homeostasis. Compared with wild
      type (WT) littermates, orexin KO mice had essentially normal amounts of sleep and
      wake, but wake and non-rapid eye movement (NREM) bouts were very brief, with many
      more transitions between all behavioral states. In constant darkness, orexin KO
      mice had normal amplitude and timing of sleep-wake rhythms, providing no evidence
      for disordered circadian control. When placed in a new, clean cage, both groups
      of mice remained awake for approximately 45 min, demonstrating that, even in the
      absence of orexin, fundamental arousal regions can be engaged to produce
      sustained wakefulness. After depriving mice of sleep for 2-8 hr, orexin KO mice
      recovered their NREM and rapid eye movement sleep deficits at comparable rates
      and to the same extent as WT mice, with similar increases in EEG delta power,
      suggesting that their homeostatic control of sleep is normal. These experiments
      demonstrate that the fragmented wakefulness of orexin deficiency is not a
      consequence of abnormal sleep homeostasis, poor circadian control, or defective
      fundamental arousal systems. Instead, the fragmented behavior of orexin KO mice
      may be best described as behavioral state instability, with apparently low
      thresholds to transition between states.

PMID- 15254085
TI  - Glutamate transporter cluster formation in astrocytic processes regulates
      glutamate uptake activity.
AB  - Glutamate is the predominant excitatory neurotransmitter in the CNS, and it is
      removed from the synaptic cleft by sodium-dependent glutamate transport activity.
      Glutamate transporter-1 (GLT-1) is expressed predominantly in astroglial cells
      and is responsible for the largest proportion of glutamate transport in the adult
      forebrain. In the present study, we demonstrate the ability of endogenous and
      recombinant GLT-1 to form clusters in astrocytic processes and characterize the
      mobility and physiological importance of these clusters in the regulation of GLT
      1 activity in the presence or absence of neurons. At the distal end of C6 glioma
      cell processes, GLT-1 clusters undergo rapid morphological changes in both shape
      and size, and these changes are inhibited by cytochalasin D treatment, suggesting
      that the morphogenesis of GLT-1 clusters is highly dependent on the actin
      network. Treatment of astrocytes with phorbol 12-myristate 13-acetate (PMA)
      quickly and preferentially decreases GLT-1 localization on the process membrane,
      leading to de novo generation of GLT-1 clusters along the process shaft.
      Pretreatment with the PKC inhibitor bisindolylmaleimide II (Bis II), with sucrose
      (0.4 m), or through the expression of a dominant-negative form of dynamin
      prevents PMA-induced GLT-1 internalization and cluster formation. In terms of
      glutamate transporter function, PMA treatment elicits a significant decrease in
      GLT-1 activity that is prevented by preexposure to either Bis II or hypertonic
      treatment. Together, these data indicate that GLT-1 trafficking and cluster
      formation in glial cell processes are dynamic events that play important roles in
      regulating glutamate uptake in astrocytes and glioma cells.

PMID- 15254086
TI  - Reanalysis of P2X7 receptor expression in rodent brain.
AB  - P2X receptors are cationic-selective ion channels gated by extracellular ATP.
      There are seven subunits (P2X1-7), the first six of which are expressed
      throughout the peripheral and central nervous systems. P2X7 receptors are rapidly
      upregulated and activated as a result of inflammatory stimuli in immune cells,
      where they act not only as cationic channels but uniquely couple with rapid
      release of proinflammatory cytokines, cytoskeletal rearrangements, and apoptosis
      or necrotic cell death. The P2X7 receptor has been termed the cytolytic non
      neuronal P2X receptor because it had not been detected in neurons until recently
      when it has been immunolocalized to several brain regions, particularly the
      hippocampus, and has been suggested to be involved in presynaptic modulation of
      transmitter release. Because its expression in brain neurons may have substantial
      functional implications, we have performed detailed immunocytochemical,
      immunoblot, and immunoprecipitation studies on brain and non-neuronal tissue
      using all currently available antibodies. We first examined rats, but staining
      patterns were inconsistent among antibodies; we therefore studied mice for which
      there are two P2X7 knock-out mice constructs available, one expressing the LacZ
      transgene. We found that P2X7 receptor protein is strongly and reliably detected
      in the submandibular gland and lung of wild-type mice but not in either of the
      P2X7-/- mice. However, we failed to find evidence for P2X7 receptor protein in
      hippocampal neurons or their input-output projections. Either the P2X7 protein in
      the hippocampus is below the limits of detection by the currently available
      methods or it is not present.

PMID- 15254087
TI  - The construction of movement with behavior-specific and behavior-independent
      modules.
AB  - Growing evidence suggests that different forms of complex motor acts are
      constructed through flexible combinations of a small number of modules in
      interneuronal networks. It remains to be established, however, whether a module
      simply controls groups of muscles and functions as a computational unit for use
      in multiple behaviors (behavior independent) or whether a module controls
      multiple salient features that define one behavior and is used primarily for that
      behavior (behavior specific). We used the Aplysia feeding motor network to
      examine the two proposals by studying the functions of identifiable interneurons.
      We identified three types of motor programs that resemble three types of
      behaviors that Aplysia produce: biting, swallowing, and rejection. Two ingestive
      programs (biting, swallowing) are defined by two movement parameters of the
      feeding apparatus (the radula): one is the same in both programs (phasing of
      radula closure motoneurons relative to radula protraction-retraction), whereas
      the other parameter (protraction duration) is different in the two programs. In
      each program, these two parameters were specified together by an individual
      neuron, but the neurons in each were different (B40 for biting, B30 for
      swallowing). These findings support the existence of behavior-specific modules.
      Furthermore, neuron B51 was found to mediate a phase that can be flexibly added
      on to both ingestive and egestive-rejection programs, suggesting that B51 may be
      a behavior-independent module. The functional interpretation of the role played
      by these modules is supported by the patterns of synaptic connectivity that they
      make. Thus, both behavior-specific and behavior-independent modules are used to
      construct complex behaviors.

PMID- 15254088
TI  - Direct action of estradiol on gonadotropin-releasing hormone-1 neuronal activity
      via a transcription-dependent mechanism.
AB  - Pulsatile secretion of gonadotropin-releasing hormone-1 (GnRH-1) is essential for
      reproduction. GnRH-1 induces gonadotropin release and is regulated by 17beta
      estradiol (E2). Although a subpopulation of GnRH-1 neurons expresses estrogen
      receptor (ER) beta, it is unclear whether E2 acts directly on GnRH-1 neurons or
      indirectly through interneuronal connections. To test the hypothesis that E2 acts
      directly on GnRH-1 neurons to regulate neuronal activity, we used calcium imaging
      to monitor intracellular calcium oscillations in GnRH-1 neurons maintained in
      nasal explants. TTX was used to minimize synaptic input from other cells.
      Consistent with previous studies, TTX reduced the activity of individual GnRH-1
      neurons to a basal level, while the population of cells maintained synchronized
      calcium oscillations. Exposure of GnRH-1 cells to TTX plus E2 increased the
      number of calcium peaks/cell, percentage of cells with > or =10 peaks, mean peak
      amplitude, and percentage of cells that contributed to each calcium pulse in
      explants maintained in vitro for 7 d (7 div) compared with TTX alone. These
      effects were induced within 30 min and were not mimicked by 17alpha-estradiol, E2
      conjugated to BSA (which does not cross the plasma membrane), or seen at 21 div,
      when the percentage of GnRH-1 cells expressing ERbeta transcripts declines. In
      addition, these effects were inhibited by the ER antagonist ICI 182,780 and
      prevented by inhibition of gene transcription. These data suggest that, via
      ERbeta, E2 can rapidly act as a hormone-activated transcription complex and are
      the first to show that E2 directly increases GnRH-1 neuronal activity and
      synchronization.

PMID- 15254089
TI  - Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent
      facilitation of P/Q-type Ca2+ channels.
AB  - Alternative splicing of the P/Q-type channel (Ca(V)2.1) promises customization of
      the computational repertoire of neurons. Here we report that concerted splicing
      of its main alpha1A subunit, at both an EF-hand-like domain and the channel C
      terminus, controls the form of Ca2+-dependent facilitation (CDF), an activity
      dependent enhancement of channel opening that is triggered by calmodulin. In
      recombinant channels, such alternative splicing switches CDF among three modes:
      (1) completely "ON" and driven by local Ca2+ influx through individual channels,
      (2) completely "OFF," and (3) partially OFF but inducible by elevated global Ca2+
      influx. Conversion from modes 1 to 3 represents an unprecedented dimension of
      control. The physiological function of these variants is likely important,
      because we find that the distribution of EF-hand splice variants is strikingly
      heterogeneous in the human brain, varying both across regions and during
      development.

PMID- 15254090
TI  - Variability in the benzodiazepine response of serotonin 5-HT1A receptor null mice
      displaying anxiety-like phenotype: evidence for genetic modifiers in the 5-HT
      mediated regulation of GABA(A) receptors.
AB  - Benzodiazepines (BZs) acting as modulators of GABA(A) receptors (GABA(A)Rs) are
      an important group of drugs for the treatment of anxiety disorders. However, a
      large inter-individual variation in BZ sensitivity occurs in the human population
      with some anxiety disorder patients exhibiting diminished sensitivity to BZ and
      reduced density of GABA(A)Rs. The mechanism underlying BZ treatment resistance is
      not known, and it is not possible to predict whether an anxiety patient will
      respond to BZ. 5-hydroxytryptamine1A receptor (5-HT1AR) null mice (R-/-) on the
      Swiss-Webster (SW) background reproduce several features of BZ-resistant anxiety;
      they exhibit anxiety-related behaviors, do not respond to BZ, have reduced BZ
      binding, and have decreased expression of the major GABA(A)R subunits alpha1 and
      alpha2. Here, we show that R-/- mice on the C57Bl6 (B6) background also have
      anxiety phenotype, but they respond to BZ and have normal GABA(A)R subunit
      expression. This indicates that the 5-HT1AR-mediated regulation of GABA(A)R alpha
      subunit expression is subject to genetic modification. Hybrid SW/B6-R-/- mice
      also exhibit BZ-resistant anxiety, suggesting that SW mice carry a genetic
      modifier, which mediates the effect of the 5-HT1AR on the expression of
      GABA(A)Ralpha subunits. In addition, we show that this genetic interaction in SW
      mice operates early in postnatal life to influence the expression of GABA(A)R
      alpha subunits at the transcriptional level. These data indicate that BZ
      resistant anxiety results from a developmental arrest of GABA(A)R expression in
      SW-R-/- mice, and a similar mechanism may be responsible for the BZ insensitivity
      of some anxiety patients.

PMID- 15254091
TI  - Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin
      signaling pathway is required for metabotropic glutamate receptor-dependent long
      term depression.
AB  - Hippocampal long-term depression (LTD) is a long-lasting decrease in synaptic
      strength that is most commonly studied at glutamatergic inputs to pyramidal cells
      in hippocampal area CA1. Activation of G-protein-coupled group I (including types
      1 and 5) metabotropic glutamate receptors (mGluRs) by the pharmacological agonist
      (RS)-3,5-dihydroxyphenylglycine (DHPG) elicits LTD in area CA1 of the
      hippocampus. Recent reports have shown that de novo protein synthesis is
      necessary for DHPG-induced LTD. However, relatively little is known about the
      signaling pathways that couple mGluRs to translation initiation. In this study,
      we investigated whether the activation of the phosphoinositide 3-kinase (PI3K)
      Akt-mammalian target of rapamycin (mTOR) pathway, which has been shown to
      regulate translation initiation, is necessary for mGluR-LTD induced by DHPG. We
      found that brief incubations of mouse hippocampal slices with DHPG resulted in
      increased phosphorylation of Akt and mTOR in hippocampal area CA1. Two
      structurally unrelated PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG
      induced increases in phosphorylation of Akt and mTOR. Biochemical fractionation
      studies showed that the DHPG-induced increase in the phosphorylation of Akt and
      mTOR could be detected in synaptoneurosome preparations, and immunohistochemical
      analysis revealed that similar increases could be detected in both stratum
      pyramidale and stratum radiatum in area CA1. Finally, we observed that both PI3K
      inhibitors and rapamycin, an mTOR inhibitor, prevented mGluR-LTD induced by DHPG.
      Together, our findings indicate that activation of the PI3K-Akt-mTOR signaling
      cascade is required for mGluR-LTD and suggest that this pathway may couple group
      I mGluRs to translation initiation in hippocampal area CA1.

PMID- 15254093
TI  - Target selection in area V4 during a multidimensional visual search task.
AB  - Natural scenes typically contain multiple objects that are unique in different
      stimulus dimensions so that an object with feature contrast to surrounding
      objects draws attention and pops out. Furthermore, if we have previous knowledge
      about the dimension in which a target object differs from the surrounding
      objects, we will attend to that dimension and more easily detect the target. Our
      aims here were to elucidate neural mechanisms underlying this type of attention
      by recording neuronal activities from area V4 and to investigate how visual
      signals encoding feature contrast between objects are modulated by attention
      specific to a particular dimension. To accomplish this, we trained monkeys to do
      a multidimensional visual search task in which two singleton stimuli, unique in
      the color or shape dimension, were presented with four other identical stimuli.
      The monkeys had to search for the singleton stimulus that was unique in the
      instructed dimension while the search dimension was switched between shape and
      color. We found that individual V4 neurons carry visual signals encoding feature
      contrast in either shape or color, and this signal is modulated depending on the
      search dimension. Population responses to the target singleton stimulus were
      significantly higher than to others, regardless of the search dimension. In most
      V4 neurons, however, significant response increases occurred only when one
      particular singleton stimulus was the target. These findings suggest that
      interaction between bottom-up signals encoding feature contrast between stimuli
      and top-down signals encoding search dimension occurs in V4 and facilitates
      adaptive selection of targets in a complex visual environment.

PMID- 15254092
TI  - The rate of cocaine administration alters gene regulation and behavioral
      plasticity: implications for addiction.
AB  - The rapid delivery of drugs of abuse to the brain is thought to promote
      addiction, but why this occurs is unknown. In the present study, we characterized
      the influence of rate of intravenous cocaine infusion (5-100 sec) on three
      effects thought to contribute to its addiction liability: its ability to block
      dopamine (DA) uptake, to activate immediate early gene expression, and to produce
      psychomotor sensitization. Rapid infusions potentiated the ability of cocaine to
      block DA reuptake, to induce c-fos and arc mRNA expression, especially in
      mesocorticolimbic regions, and to produce psychomotor sensitization. Thus, the
      rate at which cocaine is delivered influences both its neurobiological impact and
      its ability to induce a form of drug experience-dependent plasticity implicated
      in addiction. We propose that rapidly delivered cocaine may be more addictive, in
      part, because this more readily induces forms of neurobehavioral plasticity that
      lead to the compulsive pursuit of drugs.

PMID- 15254094
TI  - Subunit-specific regulation of NMDA receptor endocytosis.
AB  - At excitatory synapses, both NMDA and AMPA receptors are localized to the
      postsynaptic density (PSD). However, unlike AMPA receptors, synaptic NMDA
      receptors are stable components of the PSD. Even so, surface-expressed NMDA
      receptors undergo endocytosis, which is more robust early in development and
      declines during synaptic development. We investigated the subunit-specific
      contributions to NMDA receptor endocytosis, specifically defining the endocytic
      motifs and endocytic pathways preferred by the NR2A and NR2B subunits. We find
      that NR2A and NR2B have distinct endocytic motifs encoded in their distal C
      termini and that these interact with clathrin adaptor complexes with differing
      affinities. We also find that NR2A and NR2B sort into different intracellular
      pathways after endocytosis, with NR2B preferentially trafficking through
      recycling endosomes. In mature cultures, we find that NR2B undergoes more robust
      endocytosis than NR2A, consistent with previous studies showing that NR2A is more
      highly expressed at stable synaptic sites. Our findings demonstrate fundamental
      differences between NR2A and NR2B that help clarify developmental changes in NMDA
      receptor trafficking and surface expression.

PMID- 15254095
TI  - The amygdala is enlarged in children but not adolescents with autism; the
      hippocampus is enlarged at all ages.
AB  - Autism is a neurodevelopmental disorder characterized by impairments in
      reciprocal social interaction, deficits in verbal and nonverbal communication,
      and a restricted repertoire of activities or interests. We performed a magnetic
      resonance imaging study to better define the neuropathology of autistic spectrum
      disorders. Here we report findings on the amygdala and the hippocampal formation.
      Borders of the amygdala, hippocampus, and cerebrum were defined, and their
      volumes were measured in male children (7.5-18.5 years of age) in four diagnostic
      groups: autism with mental retardation, autism without mental retardation,
      Asperger syndrome, and age-matched typically developing controls. Although there
      were no differences between groups in terms of total cerebral volume, children
      with autism (7.5-12.5 years of age) had larger right and left amygdala volumes
      than control children. There were no differences in amygdala volume between the
      adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in
      typically developing children increases substantially in volume from 7.5 to 18.5
      years of age. Thus, the amygdala in children with autism is initially larger, but
      does not undergo the age-related increase observed in typically developing
      children. Children with autism, with and without mental retardation, also had a
      larger right hippocampal volume than typically developing controls, even after
      controlling for total cerebral volume. Children with autism but without mental
      retardation also had a larger left hippocampal volume relative to controls. These
      cross-sectional findings indicate an abnormal program of early amygdala
      development in autism and an abnormal pattern of hippocampal development that
      persists through adolescence. The cause of amygdala and hippocampal abnormalities
      in autism is currently unknown.

PMID- 15254096
TI  - Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration
      beyond sites of spinal cord injury.
AB  - Previous attempts to promote regeneration after spinal cord injury have succeeded
      in stimulating axonal growth into or around lesion sites but rarely beyond them.
      We tested whether a combinatorial approach of stimulating the neuronal cell body
      with cAMP and the injured axon with neurotrophins would propel axonal growth into
      and beyond sites of spinal cord injury. A preconditioning stimulus to sensory
      neuronal cell bodies was delivered by injecting cAMP into the L4 dorsal root
      ganglion, and a postinjury stimulus to the injured axon was administered by
      injecting neurotrophin-3 (NT-3) within and beyond a cervical spinal cord lesion
      site grafted with autologous bone marrow stromal cells. One to 3 months later,
      long-projecting dorsal-column sensory axons regenerated into and beyond the
      lesion. Regeneration beyond the lesion did not occur after treatment with cAMP or
      NT-3 alone. Thus, clear axonal regeneration beyond spinal cord injury sites can
      be achieved by combinatorial approaches that stimulate both the neuronal soma and
      the axon, representing a major advance in strategies to enhance spinal cord
      repair.

PMID- 15254097
TI  - Nociceptors lacking TRPV1 and TRPV2 have normal heat responses.
AB  - Vanilloid receptor 1 (TRPV1) has been proposed to be the principal heat
      responsive channel for nociceptive neurons. The skin of both rat and mouse
      receives major projections from primary sensory afferents that bind the plant
      lectin isolectin B4 (IB4). The majority of IB4-positive neurons are known to be
      heat-responsive nociceptors. Previous studies suggested that, unlike rat, mouse
      IB4-positive cutaneous afferents did not express TRPV1 immunoreactivity. Here,
      multiple antisera were used to confirm that mouse and rat have different
      distributions of TRPV1 and that TRPV1 immunoreactivity is absent in heat
      sensitive nociceptors. Intracellular recording in TRPV1(-/-) mice was then used
      to confirm that TRPV1 was not required for detecting noxious heat. TRPV1(-/-)
      mice had more heat-sensitive neurons, and these neurons had normal temperature
      thresholds and response properties. Moreover, in TRPV1(-/-) mice, 82% of heat
      responsive neurons did not express immunoreactivity for TRPV2, another putative
      noxious heat channel.

PMID- 15254099
TI  - Ammonia volatilization from surface-applied poultry litter under conservation
      tillage management practices.
AB  - Land application of poultry litter can provide essential plant nutrients for crop
      production, but ammonia (NH(3)) volatilization from the litter can be detrimental
      to the environment. A multiseason study was conducted to quantify NH(3)
      volatilization rates from surface-applied poultry litter under no-till and
      paraplowed conservation tillage managements. Litter was applied to supply 90 to
      140 kg N ha(-1). Evaluation of NH(3) volatilization was determined using gas
      concentrations and the flux-gradient gas transport technique using the momentum
      balance transport coefficient. Ammonia fluxes ranged from 3.3 to 24% of the total
      N applied during the winter and summer, respectively. Ammonia volatilization was
      rapid immediately after litter application and stopped within 7 to 8 d.
      Precipitation of 17 mm essentially halted volatilization, probably by
      transporting litter N into the soil matrix. Application of poultry to
      conservation-tilled cropland immediately before rainfall events would reduce N
      losses to the atmosphere but could also increase NO(3) leaching and runoff to
      streams and rivers.

PMID- 15254100
TI  - Nitrogen cycling through swine production systems: ammonia, dinitrogen, and
      nitrous oxide emissions.
AB  - Ammonia (NH(3)) emissions from animal systems have become a primary concern for
      all of livestock production. The purpose of this research was to establish the
      relationship of nitrogen (N) emissions to specific components of swine production
      systems and to determine accurate NH(3) emission factors appropriate for the
      regional climate, geography, and production systems. Micrometeorological
      instrumentation and gas sensors were placed over two lagoons in North Carolina
      during 1997-1999 to obtain information for determining ammonia emissions over
      extended periods and without interfering with the surrounding climate. Ammonia
      emissions varied diurnally and seasonally and were related to lagoon ammonium
      concentration, acidity, temperature, and wind turbulence. Conversion of
      significant quantities of ammonium NH(4)(+) to dinitrogen gas (N(2)) were
      measured in all lagoons with the emission rate largely dependent on NH(4)(+)
      concentration. Lagoon NH(4)(+) conversion to N(2) accounted for the largest loss
      component of the N entering the farm (43% as N(2)); however, small amounts of
      N(2)O were emitted from the lagoon (0.1%) and from field applications (0.05%)
      when effluent was applied nearby. In disagreement with previous and current
      estimates of NH(3) emissions from confined animal feeding operation (CAFO)
      systems, and invalidating current assumptions that most or all emissions are in
      the form of NH(3), we found much smaller NH(3) emissions from animal housing
      (7%), lagoons (8%), and fields (2%) using independent measurements of N
      transformation and transport. Nitrogen input and output in the production system
      were evaluated, and 95% of input N was accounted for as output N from the system.

PMID- 15254101
TI  - Coupled abiotic-biotic mineralization of 2,4,6-trinitrotoluene (TNT) in soil
      slurry.
AB  - The explosive 2,4,6-trinitrotoluene (TNT) is a contaminant of soils and ground
      waters worldwide. To help alleviate such environmental contamination, we
      investigated a coupled abiotic-biotic treatment scheme for remediating TNT
      contaminated soil in slurry solutions. Two types of soil were used (sandy and
      silt loam) to simulate different soils that might be found at actual sites. These
      soils were subsequently contaminated with 5000 mg kg(-1) TNT. Mineralization of
      TNT was initially optimized for minimum reactant use (Fe(3+) and H(2)O(2)) and
      maximum soil slurry percentage (percent solids) using modified Fenton reactions
      conducted in the absence of light followed by the addition of an uncharacterized
      aerobic biomass. Greater than 97% TNT degradation was observed under optimum
      reaction conditions for both soils. Using two optimum reactant concentrations for
      each soil, coupled abiotic-biotic reactions showed an increase in TNT
      mineralization, from 41 to 73% and 34 to 64% in the sandy soil (10 and 20%
      slurry, respectively, 1470 mM H(2)O(2)), and increases from 12 to 23% and 13 to
      28% in the silt loam soil (5% slurry, 294 and 1470 mM H(2)O(2), respectively).
      These results show promise in the use of combined abiotic-biotic treatment
      processes for soils contaminated with high concentrations of TNT.

PMID- 15254102
TI  - Application of a slow-release fertilizer for oil bioremediation in beach
      sediment.
AB  - A 105-d field experiment was conducted to determine the potential of the slow
      release fertilizer, Osmocote (Scotts, Marysville, OH), to stimulate the
      indigenous microbial biodegradation of petroleum hydrocarbons in an oil-spiked
      beach sediment on an intertidal foreshore in Singapore. Triplicate microcosms
      containing 80 kg of weathered sediment, spiked with 5% (w/w) Arabian light crude
      oil and 1.2% (w/w) Osmocote pellets, were established, together with control
      microcosms minus Osmocote. Relative to the control, the presence of the Osmocote
      sustained a significantly higher level of nutrients (NH(4)(+)-N, NO(3)(-)-N, and
      PO(4)(3-)-P) in the sediment pore water over the duration of the experiment. The
      metabolic activity of the indigenous microbial biomass, as measured using an
      intracellular dehydrogenase enzyme assay, was also significantly enhanced over
      the duration of the experiment in amended sediments. The loss of total
      recoverable petroleum hydrocarbons (TRPH) and biodegradation of total n-alkanes
      (C(10)-C(33)), branched alkanes (pristane and phytane), as well as total target
      polycyclic aromatic hydrocarbons (PAHs) (two- to six-ring), in both the control
      and Osmocote-amended sediments, followed a first-order biodegradation model. The
      first-order loss rate of total recoverable petroleum hydrocarbons was 2.57 times
      greater than that of the control. The hopane-normalized rate constants for total
      n-alkane, branched alkane, and total target PAH biodegradation in the Osmocote
      treated sediments were 3.95-, 5.50-, and 2.45-fold higher than the control,
      respectively. Overall, the presence of Osmocote was able to significantly enhance
      and accelerate the biodegradation of aliphatics and PAHs in oil-contaminated
      sediments under natural field conditions in an intertidal foreshore environment.

PMID- 15254103
TI  - Simulating nitrogen dynamics in agricultural soils fertilized with pig slurry and
      urea.
AB  - Within the framework of an interregional project in the Emilia Romagna region of
      northern Italy, the coupled MACRO-SOILN model was chosen to estimate soil
      protective capacity against pollutants. The aim of our study was to evaluate the
      model to better identify key parameters and processes that influence N losses in
      agricultural soils. Nitrate N content was monitored in soil under corn (Zea mays
      L.) fertilized with urea and/or pig slurry, in two field experiments performed on
      four different soils: a Fienili clay, a Barco-like silt, a Sant'Omobono silt
      loam, and a La Boaria silty clay soil. Measurements were compared with model
      predictions. For all soils, nitrate content was underestimated on average by 24
      to 88% at lower N rates; it was overestimated by 1 to 104% at higher N rates. The
      root mean square error (RMSE) was equal to 81.1%. Simulation of crop N uptake and
      soil water flow, estimation of the ammonia losses at pig slurry spreading, and N
      transformation parameter setting were considered as possible error sources. The
      calibration of crop N uptake gave rise to good model efficiency index values. The
      RMSE for the simulation of soil water content varied between 9.8 and 20.2%. A
      more accurate setting of the ammonia losses and of the feces transformation
      parameter values could allow the RMSE for the simulation of soil nitrate content
      to be reduced by no more than 10 to 15%. It is possible for the model not to
      include the simulation of processes that could have relevant effects on the soil
      N dynamics.

PMID- 15254104
TI  - Reduction of nitrate leaching with haying or grazing and omission of nitrogen
      fertilizer.
AB  - In some high-fertility, high-stocking-density grazing systems, nitrate (NO(3))
      leaching can be great, and ground water NO(3)-N concentrations can exceed maximum
      contaminant levels. To reduce high N leaching losses and concentrations,
      alternative management practices need to be used. At the North Appalachian
      Experimental Watershed near Coshocton, OH, two management practices were studied
      with regard to reducing NO(3)-N concentrations in ground water. This was
      following a fertilized, rotational grazing management practice from which ground
      water NO(3)-N concentrations exceeded maximum contaminant levels. Using four
      small watersheds (each approximately 1 ha), rotational grazing of a grass forage
      without N fertilizer being applied and unfertilized grass forage removed as hay
      were used as alternative management practices to the previous fertilized
      pastures. Ground water was sampled at spring developments, which drained the
      watershed areas, over a 7-yr period. Peak ground water NO(3)-N concentrations
      before the 7-yr study period ranged from 13 to 25.5 mg L(-1). Ground water NO(3)
      N concentrations progressively decreased under each watershed and both management
      practices. Following five years of the alternative management practices, ground
      water NO(3)-N concentrations ranged from 2.1 to 3.9 mg L(-1). Both grazing and
      haying, without N fertilizer being applied to the forage, were similarly
      effective in reducing the NO(3)-N levels in ground water. This research shows two
      management practices that can be effective in reducing high NO(3)-N
      concentrations resulting from high-fertility, high-stocking-density grazing
      systems, including an option to continue grazing.

PMID- 15254105
TI  - Tillage and manure application effects on mineral nitrogen leaching from
      seasonally frozen soils.
AB  - Land application of manure is a common practice in the Upper Midwest of the
      United States. Recently, there have been concerns regarding the effect of this
      practice on water quality, especially when manure is applied during winter over
      frozen soils. A study undertaken on a Rozetta silt loam (fine-silty, mixed,
      superactive, mesic Typic Hapludalfs) at Lancaster, WI, evaluated the effects of
      tillage and timing of manure application on surface and subsurface water quality.
      The daily scrape and haul liquid dairy manure was applied either in the fall
      (before snow) or in winter (over snow with frozen soil underneath) to be compared
      with no manure under two tillage systems (no-till and chisel-plowing). In this
      paper, we report results on the effects of the above treatments on mineral N
      leaching. Percolation and mineral N leaching during the nongrowing season were,
      respectively, 72 and 78% of the annual losses, mainly because of the absence of
      plant water and N uptake. Percolation was generally higher from no-till compared
      with chisel-plow but there was no significant effect of tillage on mineral N
      concentration of the leachate or mineral N losses via leaching. Mineral N
      leaching was statistically higher from the manure-applied vs. no-manure
      treatment, but there was no difference between winter-applied manure and no
      manure treatments. There were significant tillage by manure interactions with
      fall manure application followed by chisel-plowing resulting in highest N
      leaching losses. Averaged over the two years, N leaching rates were 52, 38, and
      28 kg N ha(-1) yr(-1) from fall-applied, winter-applied, and no-manure
      treatments, respectively. These results show that there is substantial N leaching
      from these soils even when no fertilizer or manure is applied. Furthermore, fall
      applied manure followed by fall tillage significantly increases N leaching due to
      enhanced mineralization of both soil and manure organic N.

PMID- 15254107
TI  - Effect of cobalt sorption on metal fractionation in anaerobic granular sludge.
AB  - A sequential extraction procedure was applied to two anaerobic methanogenic
      sludges (Eerbeek and Nedalco) to examine the speciation of micro- and
      macronutrients in the sludges after cobalt sorption by exposing the sludge to a 1
      mM Co solution for 4 d at pH 7 and 30 degrees C. The effect of different
      physicochemical conditions on cobalt sorption was studied as well: effect of pH
      (6-8), effect of competition by a second trace element (Ni or Fe), modification
      of the granular matrix by glutaraldehyde or heat treatment, and EDTA
      (ethylenediaminetetraacetic acid) addition. Sorbed Co was found to distribute
      between the carbonates, organic matter + sulfides, and residual fractions. Cobalt
      adsorption resulted in an antagonistic interaction with other metals present in
      the granular matrix, evidenced by the solubilization of other trace elements
      (e.g., Ni, Cu, and Zn) as well as macronutrients (especially Ca and Fe).
      Modification of the sludge matrix by glutaraldehyde or heat treatment, or
      exposure to EDTA, led to serious modifications of the Co sorption capacity and
      strong interactions with multivalent cations (i.e., Ca(2+) and Fe(2+)).

PMID- 15254106
TI  - Influence of nutrient levels on uptake and effects of mercury, cadmium, and lead
      in water spinach.
AB  - In Southeast Asia the aquatic macrophyte water spinach (Ipomoea aquatica Forsk.)
      is a popular vegetable that is cultivated in freshwater courses. These often
      serve as recipients for domestic and other sorts of wastewater that often contain
      a variety of pollutants, such as heavy metals. In addition, fertilizers are
      frequently used where water spinach is cultivated commercially for the food
      market. To estimate the importance of ambient nutrient concentrations for
      accumulation of mercury (Hg), cadmium (Cd), and lead (Pb) in water spinach,
      plants were exposed to nutrient solutions of different strength and with varying
      metal concentrations. Metal-induced toxic effects, which might possibly affect
      the yield of the plants, were also studied. The lower the nutrient strength in
      the medium was, the higher the metal concentrations that accumulated in the
      different plant parts and the lower the metal concentration in the medium at
      which metal-induced toxic effects occurred. Accordingly, internal metal
      concentrations in the plants were correlated to toxic effects. Plants exposed to
      metals retained a major proportion of the metals in the roots, which had a higher
      tolerance than shoots for high internal metal concentrations.

PMID- 15254108
TI  - Heavy metal accumulation by the halophyte species Mediterranean saltbush.
AB  - To identify Cd- and Zn-accumulating plants exhibiting a high growth rate, seeds
      from the halophyte species Mediterranean saltbush (Atriplex halimus L.) were
      collected on a heavy-metal-contaminated site in southeastern Spain (Llano del
      Beal, Cartagena). Seedlings from this ecotype were exposed for 3 wk to 0.1 mM Cd
      or Zn in a nutrient solution in a fully controlled environment. All plants
      remained alive and no significant growth inhibition was recorded until the end of
      the experiment. Mean Cd and Zn accumulation in aerial parts was 830 and 440 mg
      kg(-1), respectively, and the rate of metal translocation even increased with the
      duration of stress exposure. Resistance to heavy metals in this species may be
      partly linked to precipitation of Cd in oxalate crystals in the stems. A Cd
      induced decrease in glutathione concentration also suggests that phytochelatins
      overproduction may occur in these conditions. We conclude that Mediterranean
      saltbush, which is able to produce up to 5 Mg dry matter ha(-1) yr(-1), may be an
      effective species for phytoextraction and should be tested for this purpose in
      field conditions.

PMID- 15254109
TI  - In situ speciation studies of copper-humic substances in a contaminated soil
      during electrokinetic remediation.
AB  - Speciation of copper-humic substances (HS) in the electrokinetic remediation
      (EKR) of a contaminated soil was studied by in situ extended X-ray absorption
      fine structure (EXAFS) and X-ray absorption near edge structure (XANES)
      spectroscopies. The least-square fits of the XANES spectra suggested that the
      main Cu species in the contaminated soil were Cu-HS (50%), CuCO(3) (28%), Cu(2)O
      (11%), and CuO (11%). The Cu-HS in the contaminated soil possessed equatorial and
      axial Cu-O bond distances of 1.94 and 2.17 A with coordination numbers (CNs) of
      3.6 and 1.4, respectively. In the EKR process, the axial Cu-O bond distance in
      the Cu-HS complexes was increased by 0.15 A, which might be due to a ligand
      exchange of the Cu-HS with H(2)O molecules in the electrolyte. After 180 min of
      EKR, about 50% of the Cu-HS complexes (or 24% of total Cu) in the soil were
      dissolved and formed [Cu(H(2)O)(6)](2+) in the electrolyte, 71% (or 17% of total
      Cu in the soil) of which were migrated to the cathode under the electric field (5
      V/cm). This work exemplifies the use of in situ EXAFS and XANES spectroscopies
      for speciation studies of Cu chelated with HS in the contaminated soil during
      EKR.

PMID- 15254110
TI  - Spectroscopic speciation and quantification of lead in phosphate-amended soils.
AB  - The immobilization of Pb in contaminated soils as pyromorphite
      [Pb(5)(PO(4))(3)Cl, OH, F] through the addition of various phosphate amendments
      has gained much attention in the remediation community. However, it is difficult
      to fully determine the speciation and amount of soil Pb converted to pyromorphite
      by previously employed methods, such as selective sequential extraction
      procedures and scanning electron microscopy coupled with energy dispersive X-ray
      spectroscopy, which often lead to erroneous results in these non-equilibrated and
      heterogeneous systems. Statistical analysis by linear combination fitting (LCF)
      applied to X-ray absorption fine structure (XAFS) spectroscopic data of Pb
      contaminated soil samples relative to known Pb reference material provides
      direct, in situ evidence of dominate Pb species in the amended soils without
      chemical or physical disruption to the Pb species as well as a weighted
      quantification output. The LCF-XAFS approach illustrated that pyromorphite
      concentration ranged from 0% (control soil) to 45% (1% phosphoric acid amendment,
      residence time of 32 mo) relative to the total Pb concentration. The Pb
      speciation in the nonamended control soil included Pb-sulfur species (galena +
      angelsite = 53%), adsorbed Pb (inner-sphere + outer-sphere + organic-bound =
      45%), and Pb-carbonate phases (cerussite + hydrocerussite = 2%). The addition of
      P promoted pyromorphite formation and the rate of formation increased with
      increasing P concentration (up to 45%). The supplemental addition of an iron
      amendment as an iron-rich byproduct with triple superphosphate (TSP) enhanced
      pyromorphite formation relative to independent TSP amendment of like
      concentrations (41 versus 29%). However, the amendment of biosolids and biosolids
      plus TSP observed little pyromorphite formation (1-16% of total Pb), but a
      significant increase of sorbed Pb was determined by LCF-XAFS.

PMID- 15254111
TI  - Transport and fate of nitrate in headwater agricultural streams in Illinois.
AB  - Nitrogen inputs to the Gulf of Mexico have increased during recent decades and
      agricultural regions in the upper Midwest, such as those in Illinois, are a major
      source of N to the Mississippi River. How strongly denitrification affects the
      transport of nitrate (NO(3)-N) in Illinois streams has not been directly
      assessed. We used the nutrient spiraling model to assess the role of in-stream
      denitrification in affecting the concentration and downstream transport of NO(3)
      N in five headwater streams in agricultural areas of east-central Illinois.
      Denitrification in stream sediments was measured approximately monthly from April
      2001 through January 2002. Denitrification rates tended to be high (up to 15 mg N
      m(-2) h(-1)), but the concentration of NO(3)-N in the streams was also high (>7
      mg N L(-1)). Uptake velocities for NO(3)-N (uptake rate/concentration) were lower
      than reported for undisturbed streams, indicating that denitrification was not an
      efficient N sink relative to the concentration of NO(3)-N in the water column.
      Denitrification uptake lengths (the average distance NO(3)-N travels before being
      denitrified) were long and indicated that denitrification in the streambed did
      not affect the transport of NO(3)-N. Loss rates for NO(3)-N in the streams were
      <5% d(-1) except during periods of low discharge and low NO(3)-N concentration,
      which occurred only in late summer and early autumn. Annually, most NO(3)-N in
      these headwater sites appeared to be exported to downstream water bodies rather
      than denitrified, suggesting previous estimates of N losses through in-stream
      denitrification may have been overestimated.

PMID- 15254112
TI  - Remediating munitions-contaminated soil with zerovalent iron and cationic
      surfactants.
AB  - Soils contaminated from military operations often contain mixtures of HMX
      (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), RDX (hexahydro-1,3,5-trinitro
      1,3,5-triazine), and TNT (2,4,6-trinitrotoluene) rather than a single explosive.
      Differences among explosives in solubility and reactivity make developing a
      single remediation treatment difficult. When Fe(0) was used to treat a munitions
      contaminated soil, we observed high rates of destruction for RDX and TNT (98%)
      but not HMX. Our objective was to determine if HMX destruction by Fe(0) could be
      enhanced by increasing HMX solubility by physical (temperature) or chemical
      (surfactants) means. To determine electron acceptor preference, we treated RDX
      and HMX with Fe(0) in homogeneous solutions and binary mixtures. Increasing
      aqueous temperature (20 to 55 degrees C) increased HMX solubility (2 to 22 mg L(
      1)) but did not increase destruction by Fe(0) in a contaminated soil slurry that
      also contained RDX and TNT. Batch experiments using equal molar concentrations of
      RDX and HMX demonstrated that RDX was preferentially reduced over HMX by Fe(0).
      By testing various surfactants, we found that the cationic surfactants (HDTMA
      [hexadecyltrimethylammonium bromide], didecyl, and didodecyl) were most effective
      in increasing HMX concentration in solution. Didecyl and HDTMA were also found to
      be highly effective in facilitating the transformation of HMX by Fe(0). Using
      HDTMA or didecyl solutions (3%, w/v) containing solid-phase HMX, we observed that
      100% of the added HMX was transformed by Fe(0) in the didecyl matrix and 60% in
      the HDTMA matrix. These results indicate that cationic surfactants can increase
      HMX solubility and facilitate Fe(0)-mediated transformation kinetics but HMX
      destruction rates will be slowed when RDX is present.

PMID- 15254113
TI  - Sorption of apolar aromatic compounds to soil humic acid particles affected by
      aluminum(III) ion Cross-Linking.
AB  - Sorption of hydrophobic compounds in soils often shows nonlinearity, competition,
      and hysteresis. Since such behaviors have been associated with organic polymers
      in glassy state, it has been postulated that some forms of soil humic substances
      are glassy. The glassy state is favored by properties that decrease the
      flexibility of macromolecules, such as cross-linking, presence of unsaturated
      bonds, and high molecular weight. Polyvalent metal ions, which are abundant in
      soils, may cross-link humic substances by coordinating to multiple functional
      groups on different strands. Accordingly, we prepared an Al(3+)-cross-linked
      humic acid (Al-HA) from the H(+) form (H-HA) of a soil humic acid by a
      flocculation technique that leaves Al ions bound to organic groups. Sorption of
      naphthalene and 1,2,4-trichlorobenzene (TCB) on H-HA was nonlinear, competitive,
      and slightly hysteretic, in agreement with previous studies showing glass
      transition temperatures of humic acids that lie above room temperature.
      Nonlinearity, competition, and hysteresis were all enhanced in Al-HA, validating
      the hypothesis that metal ion cross-linking enhances nonideal sorption.
      Application of a glassy polymer sorption model reveals that cross-linking
      increases the affinity of solutes for the hole domain relative to the dissolution
      domain. The results (i) indicate that isolated, purified soil humic acid behaves
      like a glassy solid, (ii) indicate that metal-ion cross-linking creates a more
      rigid-chain structure and supports a link between nonideal sorption and the
      glassy character of soil organic matter, and (iii) underscore the importance of
      metal ions on humic structure in relation to sorption of hydrophobic organic
      compounds.

PMID- 15254114
TI  - Cation-pi bonding: a new perspective on the sorption of polycyclic aromatic
      hydrocarbons to mineral surfaces.
AB  - Recent molecular modeling and spectroscopic studies have suggested that
      relatively strong interactions can occur between aromatic pi donors and metal
      cations in aqueous solutions. The objective of this study was to characterize
      potential cation-pi interactions between pi donors and exchangeable cations
      accumulated at mineral surfaces via both spectroscopic and batch sorption
      methods. Quadrupolar splitting in deuterium nuclear magnetic resonance ((2)H NMR)
      spectroscopy for d(2)-dichloromethane, d(6)-benzene, and d(8)-toluene (C(6)D(5)-
      moiety) in aqueous suspensions of a Na-saturated reference montmorillonite
      unambiguously indicated the ordering of solute molecules with respect to the clay
      surface. The half line broadening (Delta nu(1/2)) of (2)H NMR of d(6)-benzene in
      montmorillonite suspensions showed that soft exchangeable cations generally
      resulted in more benzene sorption compared with harder cations (e.g., Ag(+) >
      Cs(+) > Na(+) > Mg(2+), Ba(2+)). In batch sorption experiments, saturating
      minerals (e.g., porous silica gels, kaolinite, vermiculite, montmorillonite) with
      a soft transition metal or softer base cations generally increased the polycyclic
      aromatic hydrocarbon (PAH) sorption relative to harder cations (e.g., Ag(+) >>
      Cs(+) > K(+) > Na(+); Ba(2+) > Mg(2+)). Sorption of phenanthrene to Ag(+)
      saturated montmorillonite was much stronger compared with 1,2,4,5
      tetrachlorobenzene, a coplanar non-pi donor having slightly higher
      hydrophobicity. In addition, a strong positive correlation was found between the
      cation-dependent sorption and surface charge density of the minerals (e.g.,
      vermiculite, montmorillonite >> silica gels, kaolinite). These results, coupled
      with the observations in (2)H NMR experiments with montmorillonite, strongly
      suggest that cation-pi bonding forms between PAHs and exchangeable cations at
      mineral surfaces and affects PAH sorption to hydrated mineral surfaces.

PMID- 15254115
TI  - Sorption of sulfonamide pharmaceutical antibiotics on whole soils and particle
      size fractions.
AB  - Residues of pharmaceutical antibiotics are found in the environment, whose fate
      and effects are governed by sorption. Thus, the extent and mechanisms of the soil
      sorption of p-aminobenzoic acid and five sulfonamide antibiotics (sulfanilamide,
      sulfadimidine, sulfadiazine, sulfadimethoxine, and sulfapyridine) were
      investigated using topsoils of fertilized and unfertilized Chernozem and their
      organic-mineral particle-size fractions. Freundlich adsorption coefficients
      (K(f)) ranged from 0.5 to 6.5. Adsorption increased with aromaticity and
      electronegativity of functional groups attached to the sulfonyl-phenylamine core.
      Adsorption to soil and particle-size fractions increased in the sequence: coarse
      silt < whole soil < medium silt < sand < clay < fine silt and was influenced by
      pH. Sorption nonlinearity (1/n </= 0.76) indicated specific interactions with
      functional groups of soil organic matter (SOM). Phenolic and carboxylic groups, N
      heterocyclic compounds, and lignin decomposition products were tentatively
      assigned as preferred binding sites using statistical analysis of pyrolysis-mass
      spectra and adsorption coefficients. Adsorption of sulfonamides to mineral soil
      colloids was weaker and resulted in a stronger desorption from clay-size
      fractions. Moreover, steric accessibility of organic-mineral complexes in clay
      size fractions was significantly reduced. With a quantitative structure-property
      relationship (QSPR) model, combining the organic carbon concentration, the
      sulfonamides' chromatographic capacity factor (k'), and nondissociated species
      concentration (CF(a)), distribution coefficients (K(d)) were estimated with a
      cross-validated regression coefficient Q(2) = 0.71. Modeling and molecular
      mechanics calculations of antibiotic-SOM complexes showed preferred site-specific
      sorption via hydrogen bonds and van der Waals interactions. Distinct chemical
      structural properties, such as aromaticity and van der Waals volumes, correlated
      with the sorption data.

PMID- 15254116
TI  - Polycyclic aromatic hydrocarbon release from a soil matrix in the in vitro
      gastrointestinal tract.
AB  - Soil ingestion is an important exposure route by which immobile soil contaminants
      enter the human body. We assessed polycyclic aromatic hydrocarbon (PAH) release
      from a contaminated soil, containing 49 mg PAH kg(-1), using a SHIME (Simulator
      of the Human Intestinal Microbial Ecosystem) reactor comprising the stomach,
      duodenal, and colon compartments. Polycyclic aromatic hydrocarbon release was
      defined as that fraction remaining in the digest supernatant after centrifugation
      for 5 min at 1500 x g. The PAH release in the stomach digest was only 0.44% of
      the total PAH present in soil, resulting in PAH concentrations of 23 micrograms
      PAH L(-1) chyme. The lower PAH releases in duodenum (0.13%) and colon (0.30%)
      digests, compared with the stomach digest, were thought to be attributed to
      combined complexation and precipitation with bile salts, dissolved organic
      matter, or colon microbiota. We studied these complexation processes in an
      intestinal suspension more in depth by preparing mixtures of 9
      anthracenepropionic acid, a Bacillus subtilis culture, and cholin as model
      compounds for PAHs, organic matter, and bile salts, respectively. Bile salts or
      organic matter in the aqueous phase initially enhance PAH desorption from soil.
      However, desorbed PAHs may form large aggregates with bile and organic matter,
      lowering the freely dissolved PAH fraction in the supernatant. Using the model
      compounds, mathematical equations were developed and validated to predict PAH
      complexation processes in the gastrointestinal tract. Contaminant release and
      subsequent complexation in the gut is an important prerequisite to intestinal
      absorption and thus bioavailability of that contaminant. The data from this
      research may help in understanding the processes to which PAHs are subjected in
      the gastrointestinal tract, before intestinal absorption.

PMID- 15254117
TI  - Factors controlling sorption of prosulfuron by variable-charge soils and model
      sorbents.
AB  - Prosulfuron [1-(4-methoxy-6-methyltriazin-2-yl)-3-[2-(3,3,3-trifluoropropyl)
      phenylsulfonyl]-urea), a relatively new sulfonylurea herbicide, is a weak acid
      (pK(a) 3.76), and therefore, will undergo pH-dependent speciation and sorption.
      Understanding prosulfuron sorption in soils is important for predicting its
      environmental fate. Soil and solution factors controlling sorption were
      investigated by measuring prosulfuron sorption on five model sorbents (amorphous
      silica, alpha-alumina, CaSWy1 montmorillonite, commercial humic acid, and anion
      exchange resin) and 10 variable-charge soils from CaCl(2) and Ca(H(2)PO(4))(2)
      solutions as a function of pH and ionic strength. Anion exchange of prosulfuron
      accounted for up to 82% of overall sorption in the pH range from 3 to 7. The
      relative importance of anion exchange to prosulfuron sorption was positively
      correlated to the ratio of anion and cation exchange capacities. Comparison
      between organic carbon (OC)-normalized sorption (K(oc)) versus pH for humic acid
      and variable-charge soils show similar trends with sorption decreasing with
      increasing pH. However, K(oc) values estimated from variable-charge soils in the
      lower pH range where anion exchange has the greatest contribution to sorption was
      almost one log unit greater than that estimated from humic acid clearly
      exemplifying the impact of anion exchange. Similarity in K(oc)-pH curves for
      humic acid and variable-charge soils may result from the fact that (i) cation
      exchange capacity increases with increasing OC content, thus effective anion
      exchange capacity is reduced; and (ii) the relative contribution of hydrophobic
      and hydrophilic sorption mechanisms was fairly constant. Given that both
      hydrophilic and hydrophobic sorption of prosulfuron decrease with increasing pH,
      addition of fertilizer and lime amendments may enhance the potential for off-site
      leaching of recently applied acidic pesticides.

PMID- 15254118
TI  - Sorption and stability of the polycyclic nitramine explosive CL-20 in soil.
AB  - The polycyclic nitramine CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12
      hexaazaisowurtzitane) is being considered for use as a munition, but its
      environmental fate and impact are unknown. The present study consisted of two
      main elements. First, sorption-desorption data were measured with soils and
      minerals to evaluate the respective contributions of organic matter and minerals
      to CL-20 immobilization. Second, since CL-20 hydrolyzes at a pH of >7, the effect
      of sorption on CL-20 degradation was examined in alkaline soils. Sorption
      desorption isotherms measured using five slightly acidic soils (5.1 < pH < 6.9)
      containing various amounts of total organic carbon (TOC) revealed a nonlinear
      sorption that increased with TOC [K(d) (0.33% TOC) = 2.4 L kg(-1); K(d) (20% TOC)
      = 311 L kg(-1)]. Sorption to minerals (Fe(2)O(3), silica, kaolinite,
      montmorillonite, illite) was very low (0 < K(d) < 0.6 L kg(-1)), suggesting that
      mineral phases do not contribute significantly to CL-20 sorption. Degradation of
      CL-20 in sterile soils having different pH values increased as follows: sandy
      agricultural topsoil from Varennes, QC, Canada (VT) (pH = 5.6; K(d) = 15 L kg(
      1); 8% loss) < clay soil from St. Sulpice, QC, Canada (CSS) (pH = 8.1; K(d) = 1 L
      kg(-1); 82% loss) < sandy soil provided by Agriculture Canada (SAC) (pH = 8.1,
      K(d) = approximately 0 L kg(-1); 100% loss). The faster degradation in SAC soil
      compared with CSS soil was attributed to the absence of sorption in the former.
      In summary, CL-20 is highly immobilized by soils rich in organic matter. Although
      sorption retards abiotic degradation, CL-20 still decomposes in soils where pH is
      >7.5, suggesting that it will not persist in even slightly alkaline soils.

PMID- 15254119
TI  - Differences in the effects of simulated sea aerosol on water relations, salt
      content, and leaf ultrastructure of rock-rose plants.
AB  - White-leaf rock-rose (Cistus albidus L.) and Montpellier rock-rose (C.
      monspeliensis L.) plants were sprayed 2 to 3 min per day over a 7-d period, in an
      unheated plastic greenhouse, with different aqueous solutions containing
      deionized water alone (control); an anionic surfactant (sodium
      dodecylbenzenesulfonate 82.5%, 50 mg L(-1)) (S1); a solution simulating the
      composition of sea aerosol (S2); and a solution simulating sea aerosol with
      anionic surfactant (S3). White-leaf rock-rose was more sensitive to sea aerosol,
      showing greater leaf damage and markedly decreased growth, and the presence of
      surfactant enhanced the phytotoxic effect leading to greater increases in
      mortality. Montpellier rock-rose did not appear to be more adversely affected
      when surfactant was used in combination with sea aerosol, and manifested slight
      or less severe symptoms than white-leaf rock-rose. There was a significant
      increase in leaf turgor potential in the plants treated with both sea aerosol
      treatments by osmotic adjustment effect. The decrease in photosynthesis level
      seems to be due to both stomatal and nonstomatal factors. The results of
      microscopical analysis of Montpellier rock-rose plants show that sea aerosol
      treatment caused alterations in the chloroplast structure, reducing the starch
      grain and swelling the thylakoid membranes. The results of this study indicated
      that Montpellier rock-rose was more tolerant to sea aerosol than white-leaf rock
      rose, showing a lower reduction in plant growth and less leaf damage, probably
      because of its ability to compartmentalize the toxic ions at the intracellular
      level.

PMID- 15254120
TI  - Herbicide selection of Italian ryegrass under different levels of UVB radiation.
AB  - Ultraviolet-B radiation is an environmental stress for plants and this situation
      could become aggravated in the next decades. In this study we used Italian
      ryegrass (Lolium multiflorum Lam.) as a model system to test whether an
      environmental stress derived from global change, such as UVB, can influence the
      efficacy of control procedures and evolution toward herbicide resistance. We grew
      three generations of Italian ryegrass plants with and without UVB light and
      subjected them to a series of diclofop-methyl [(+/-)-2-[4-(2,4-dichlorophenoxy)
      phenoxy] propanoic acid, methyl ester] doses. The effect of selection history was
      tested with herbicide dose response. The effect of herbicide application on plant
      survival and biomass varied significantly among herbicide doses and with absence
      or presence of UVB light. In the absence of herbicide, the decrease in individual
      fecundity with increasing plant density was similar under both no-UVB and UVB
      light treatments. Only plants growing without UVB light increased production of
      reproductive structures in response to the decrease in density caused by
      herbicide application. Our study shows that UVB light was a weak stress factor
      for the ryegrass plants. However, when herbicide selection pressure was high, UVB
      light reduced the evolution toward herbicide tolerance. When selection pressure
      on the parental plants was lower, the two stress factors had a synergistic
      effect, causing changes in herbicide efficacy that in turn had demographic and
      evolutionary consequences. In the field, these interactions between stress
      factors might be of significance for annual weeds in which seed output is a major
      determinant in fitness.

PMID- 15254121
TI  - In situ dynamics of phosphorus in the rhizosphere solution of five species.
AB  - Root activity can modify the chemistry of the rhizosphere and alter phosphorus
      (P) availability and uptake. However, until recently, relatively little was known
      about the dynamics of soil solution P at the root surface because of our
      inability to measure in situ changes in solution P at the plant root. A mini
      rhizotron experiment with corn (Zea mays L. cv. Stine 2250), soybean [Glycine max
      (L.) Merr. cv. Pioneer 3563), cottonwood (Populus deltoids L.), smooth brome
      (Bromus inermis Leyss.), and switchgrass (Panicum virgatum L.) was conducted to
      measure the spatial and temporal dynamics of P in the rhizosphere solution of a
      fine silty, P-rich calcareous soil (solid-phase total P concentration = 62 mg kg(
      1), pH = 7.68) from western Iowa. Micro-suction cups were used to collect samples
      of soil solution from defined segments of the rhizosphere, and capillary
      electrophoresis (CE) was used to determine the P concentration of the soil
      solution. At the end of 10 d, a decreasing P concentration gradient in soil
      solution toward the root was observed in corn, cottonwood, and smooth brome. No
      clear rhizosphere effect was observed for soybean and switchgrass. Statistical
      analysis indicated significantly lower solution P concentrations in the
      rhizospheres of corn (p = 0.05), cottonwood (p = 0.01), and smooth brome (p =
      0.01) compared with bulk soil solution. Results indicate that P depletion from
      rhizosphere soil solution depends on plant species. Under the conditions of this
      study, corn, cottonwood, and smooth brome were more effective in depleting
      solution P than soybean and switchgrass.

PMID- 15254122
TI  - Phosphorus desorption dynamics in soil and the link to a dynamic concept of
      bioavailability.
AB  - Soils under intensive livestock farming and heavily fertilized with animal manure
      may have elevated soil phosphorus (P) contents. We determined P desorption
      kinetics in batch experiments using soils from a pot experiment where grass was
      cropped on a P-rich noncalcareous sandy soil without P addition, to lower the
      soil P content. A diffusion model was used to describe P desorption kinetics from
      a spherical aggregate. The model was calibrated with data from the batch
      experiments. Simulation results show that in the pot experiment, P desorption
      from the solid phase of the inner layers was initially far from equilibrium with
      the rest of the aggregate, but desorption came closer to equilibrium as the soil
      P content decreased further. A simple tool is presented, referred to as the
      dynamic bioavailability index (DBI), to determine whether kinetics of P
      desorption limits plant uptake. This tool is the dimensionless ratio of the
      modeled maximal diffusive flux from soil aggregates to solution and the plant
      uptake rate measured in the pot experiment. The DBI was initially much larger
      than one; the maximal possible P desorption rate exceeded the uptake rate, so
      uptake was not limited by desorption. The DBI stabilized at a value somewhat
      larger than one after a while, due to soil transport limitations. This decrease
      coincided with a large decrease of the P content in the grass to a value (far)
      below what is considered as optimal; the supply rate of P from soil to the root
      cannot meet the demand needed for optimal P uptake. The DBI could be seen as a
      promising onset to a new dynamic approach of bioavailability.

PMID- 15254123
TI  - Potential loss of phosphorus from a rice field in Taihu Lake basin.
AB  - Nonpoint-source pollution by phosphorus (P) poses a threat to waters in the Taihu
      Lake basin in China. The potential transfer of P in rice (Oryza sativa L.) fields
      through surface drainage and subsurface flow was investigated under simulated
      conventional irrigation-drainage management. Surface drainage events were
      conducted to avoid overflow across the plots after heavy rainfall and for rice
      harvest, at which time P losses were also investigated. This study was conducted
      in 2001 in a long-term rice field experiment. The experimental plots were treated
      with 0, 26, or 52 kg P ha(-1) as superphosphate or 26 kg P ha(-1) with equal
      parts of P supplied as superphosphate and pig manure. Phosphorus concentrations
      and loads in field floodwater on plots receiving P rapidly declined in a
      nonlinear manner before the first drainage, three weeks after fertilizer
      application. The combined application of fertilizer and manure P resulted in
      higher P transfer potential in field floodwater than with fertilizer P alone one
      week after P application. Phosphorus concentrations in interflow water sampled by
      Teflon suction cups inserted at a depth of 150 to 200 mm gradually increased
      within two weeks after P application, then declined. The concentration of P in
      interflow water was related to soil P buildup from long-term P application, as
      well as recently applied P. The 26 kg P ha(-1) treatment (the conventional P rate
      in this region) resulted in a loss of 0.74 kg total phosphorus (TP) ha(-1) and a
      drainage-weighted average concentration of 0.25 mg TP L(-1) from the three
      surface drainage events. Results indicate that avoiding overflow drainage after P
      input and extending the time between P application and drainage may reduce P
      losses from rice paddies.

PMID- 15254124
TI  - Evaluation of phosphorus transport in surface runoff from packed soil boxes.
AB  - Evaluation of phosphorus (P) management strategies to protect water quality has
      largely relied on research using simulated rainfall to generate runoff from
      either field plots or shallow boxes packed with soil. Runoff from unmanured,
      grassed field plots (1 m wide x 2 m long, 3-8% slope) and bare soil boxes (0.2 m
      wide and 1 m long, 3% slope) was compared using rainfall simulation (75 mm h(-1))
      standardized by 30-min runoff duration (rainfall averaged 55 mm for field plots
      and 41 mm for packed boxes). Packed boxes had lower infiltration (1.2 cm) and
      greater runoff (2.9 cm) and erosion (542 kg ha(-1)) than field plots (3.7 cm
      infiltration; 1.8 cm runoff; 149 kg ha(-1) erosion), yielding greater total
      phosphorus (TP) losses in runoff. Despite these differences, regressions of
      dissolved reactive phosphorus (DRP) in runoff and Mehlich-3 soil P were
      consistent between field plots and packed boxes reflecting similar buffering by
      soils and sediments. A second experiment compared manured boxes of 5- and 25-cm
      depths to determine if variable hydrology based on box depth influenced P
      transport. Runoff properties did not differ significantly between box depths
      before or after broadcasting dairy, poultry, or swine manure (100 kg TP ha(-1)).
      Water-extractable phosphorus (WEP) from manures dominated runoff P, and
      translocation of manure P into soil was consistent between box types. This study
      reveals the practical, but limited, comparability of field plot and soil box
      data, highlighting soil and sediment buffering in unamended soils and manure WEP
      in amended soils as dominant controls of DRP transport.

PMID- 15254125
TI  - Runoff phosphorus losses as related to phosphorus source, application method, and
      application rate on a Piedmont soil.
AB  - Land application of animal manures and fertilizers has resulted in an increased
      potential for excessive P losses in runoff to nutrient-sensitive surface waters.
      The purpose of this research was to measure P losses in runoff from a bare
      Piedmont soil in the southeastern United States receiving broiler litter or
      inorganic P fertilizer either incorporated or surface-applied at varying P
      application rates (inorganic P, 0-110 kg P ha(-1); broiler litter, 0-82 kg P ha(
      1)). Rainfall simulation was applied at a rate of 76 mm h(-1). Runoff samples
      were collected at 5-min intervals for 30 min and analyzed for reactive phosphorus
      (RP), algal-available phosphorus (AAP), and total phosphorus (TP). Incorporation
      of both P sources resulted in P losses not significantly different than the
      unfertilized control at all application rates. Incorporation of broiler litter
      decreased flow-weighted concentration of RP in runoff by 97% and mass loss of TP
      in runoff by 88% compared with surface application. Surface application of
      broiler litter resulted in runoff containing between 2.3 and 21.8 mg RP L(-1) for
      application rates of 8 to 82 kg P ha(-1), respectively. Mass loss of TP in runoff
      from surface-applied broiler litter ranged from 1.3 to 8.5 kg P ha(-1) over the
      same application rates. Flow-weighted concentrations of RP and mass losses of TP
      in runoff were not related to application rate when inorganic P fertilizer was
      applied to the soil surface. Results for this study can be used by P loss
      assessment tools to fine-tune P source, application rate, and application method
      site factors, and to estimate extreme-case P loss from cropland receiving broiler
      litter and inorganic P fertilizers.

PMID- 15254126
TI  - Surface runoff losses of phosphorus from Virginia soils amended with turkey
      manure using phytase and high available phosphorus corn diets.
AB  - Many states have passed legislation that regulates agricultural P applications
      based on soil P levels and crop P uptake in an attempt to protect surface waters
      from nonpoint P inputs. Phytase enzyme and high available phosphorus (HAP) corn
      supplements to poultry feed are considered potential remedies to this problem
      because they can reduce total P concentrations in manure. However, less is known
      about their water solubility of P and potential nonpoint-source P losses when
      land-applied. This study was conducted to determine the effects of phytase enzyme
      and HAP corn supplemented diets on runoff P concentrations from pasture soils
      receiving surface applications of turkey manure. Manure from five poultry diets
      consisting of various combinations of phytase enzyme, HAP corn, and normal phytic
      acid (NPA) corn were surface-applied at 60 kg P ha(-1) to runoff boxes containing
      tall fescue (Festuca arundinacea Schreb.) and placed under a rainfall simulator
      for runoff collection. The alternative diets caused a decrease in manure total P
      and water soluble phosphorus (WSP) compared with the standard diet. Runoff
      dissolved reactive phosphorus (DRP) concentrations were significantly higher from
      HAP manure-amended soils while DRP losses from other manure treatments were not
      significantly different from each other. The DRP concentrations in runoff were
      not directly related to manure WSP. Instead, because the mass of manure applied
      varied for each treatment causing different amounts of manure particles lost in
      runoff, the runoff DRP concentrations were influenced by a combination of runoff
      sediment concentrations and manure WSP.

PMID- 15254127
TI  - Sources and transformations of nitrogen compounds along the Lower Jordan River.
AB  - The Lower Jordan River is located in the semiarid area of the Jordan Valley,
      along the border between Israel and Jordan. The implementation of the water
      sections of the peace treaty between Israel and Jordan and the countries'
      commitment to improve the ecological sustainability of the river system require a
      better understanding of the riverine environment. This paper investigates the
      sources and transformations of nitrogen compounds in the Lower Jordan River by
      applying a combination of physical, chemical, isotopic, and mathematical
      techniques. The source waters of the Lower Jordan River contain sewage, which
      contributes high ammonium loads to the river. Ammonium concentrations decrease
      from 20 to 0-5 mg N L(-1) along the first 20 km of the Lower Jordan River, while
      nitrate concentrations increase from nearly zero to 10-15 mg N L(-1), and
      delta(15)N (NO(3)) values increase from less than 5 per thousand to 15-20 per
      thousand. Our data analysis indicates that intensive nitrification occurs along
      the river, between 5 and 12 km from the Sea of Galilee, while further downstream
      nitrate concentration increases mostly due to an external subsurface water source
      that enters the river.

PMID- 15254128
TI  - Relationship between soil test phosphorus and phosphorus in runoff: effects of
      soil series variability.
AB  - Phosphorus loss in runoff from agricultural fields has been identified as an
      important contributor to eutrophication. The objective of this research was to
      determine the relationship between phosphorus (P) in runoff from a benchmark soil
      (Cecil sandy loam; fine, kaolinitic, thermic Typic Kanhapludult) and Mehlich III
      , deionized water-, and Fe(2)O(3)-extractable soil P, and degree of phosphorus
      saturation (DPS). Additionally, the value of including other soil properties in P
      loss prediction equations was evaluated. Simulated rainfall was applied (75 mm h(
      1)) to 54 1-m(2) plots installed on six fields with different soil test
      phosphorus (STP) levels. Runoff was collected in its entirety for 30 min and
      analyzed for total P and dissolved reactive phosphorus (DRP). Soil samples were
      collected from 0- to 2-, 0- to 5-, and 0- to 10-cm depths. The strongest
      correlation for total P and DRP occurred with DPS (r(2) = 0.72). Normalizing DRP
      by runoff depth resulted in improved correlation with deionized water-extractable
      P for the 0- to 10-cm sampling depth (r(2) = 0.81). The STP levels were not
      different among sampling depths and analysis of the regression equations revealed
      that soil sampling depth had no effect on the relationship between STP and P in
      runoff. For all forms of P in runoff and STP measures, the relationship between
      STP and runoff P was much stronger when the data were split into groups based on
      the ratio of oxalate-extractable Fe to Al. For all forms of P in runoff and all
      STP methods, R(2) increased with the inclusion of oxalate-extractable Al and Fe
      in the regression equation. The results of this study indicate that inclusion of
      site-specific information about soil Al and Fe content can improve the
      relationship between STP and runoff P.

PMID- 15254129
TI  - Colloidal phosphorus in surface runoff and water extracts from semiarid soils of
      the western United States.
AB  - Colloidal particles in runoff may have an important role in P transfer from soils
      to waterbodies, but remain poorly understood. We investigated colloidal molybdate
      reactive phosphorus (MRP) in surface runoff and water extracts of calcareous
      arable soils from the semiarid western United States. Colloidal MRP was
      determined by ultrafiltration and operationally defined as MRP associated with
      particles between 1 microm and 1 nm diameter, although a smaller pore-size filter
      (0.3 nm) was used to define the lower size limit of colloids in water extracts.
      In surface runoff from three calcareous soils generated by simulated sprinkler
      irrigation, colloidal MRP concentrations ranged between 0.16 and 3.07 microM,
      constituting between 11 and 56% of the MRP in the <1-microm fraction.
      Concentrations were strongly correlated with agronomic and environmental soil
      test P concentrations for individual soils. Water extracts of a range of similar
      soils contained two size fractions of colloidal MRP: a larger fraction (1.0-0.2
      microm) probably associated with fine clays, and a smaller fraction (3-0.3 nm)
      probably associated with Ca-phosphate minerals. Colloidal MRP was solubilized in
      the acidic medium of the colorimetric detection procedure, suggesting that a
      fraction of the filterable MRP in runoff from calcareous soils may not be as
      readily bioavailable as free phosphate in waterbodies. Our results suggest that
      colloidal MRP is an important but poorly understood component of P transfer in
      runoff from calcareous western U.S. soils and should be given greater
      consideration in mechanistic studies of the P transfer process.

PMID- 15254130
TI  - Preferential flow of bromide, bentazon, and imidacloprid in a Dutch clay soil.
AB  - Leaching to ground water and tile drains are important parts of the environmental
      assessment of pesticides. The aims of the present study were to (i) assess the
      significance of preferential flow for pesticide leaching under realistic worst
      case conditions for Dutch agriculture (soil profile with thick clay layer and
      high rainfall) and (ii) collect a high-quality data set that is suitable for
      testing pesticide leaching models. The movement of water, bromide, and the
      pesticides bentazon [3-isopropyl-1H-2, 1,3-benzothiadiazine-4(3H)-one-2,2
      dioxide] and imidacloprid [1-[(6-chloro-3-pyridinyl)-methyl]-N-nitro-2
      imidazolidinimine] was monitored in a clay soil for about 1 yr. The 1.2-ha field
      was located in the central part of the Netherlands (51 degrees 53' N, 5 degrees
      43' E). The soil was a Eutric Fluvisol cropped with winter wheat (Triticum
      aestivum L.). Tile drains were present at a 0.8- to 0.9-m depth and the ground
      water level fluctuated between a 0.5- and 2-m depth. All chemicals were applied
      in spring. None of the soil concentration profiles showed bimodal concentration
      distributions. However, for each substance the highest concentration in drain
      water was found in the first drainage event after its application, which
      indicates preferential flow. This preferential flow is probably caused by
      permanent macropores that were present in the 0.3- to 1.0-m layer. At the time of
      the first drainage event, the drain water concentration of each substance was
      about an order of magnitude higher than its ground water concentration. Thus, the
      flux concentrations in drain water proved to be a more sensitive detector of
      preferential flow than the resident concentrations in the soil profile and the
      ground water.

PMID- 15254131
TI  - Assessing ground water vulnerability with the type transfer function model in the
      San Joaquin Valley, California.
AB  - The recently developed type transfer function (TTF) simulation approach was
      applied to generate a regional-scale nonpoint-source ground water vulnerability
      assessment for the San Joaquin Valley, California. The computationally
      comparatively inexpensive TTF approach produces quantitative estimates of
      contaminant concentrations for large regional scales through characteristic
      functions based on different soil textures and their leaching properties. The TTF
      simulations employed an extensive soil and recharge database to estimate atrazine
      (1-chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine) concentrations at a
      compliance depth of 3 m resulting from a surface application. Two different sets
      of TTFs with two different levels of upscaling were used for spatially uniform
      and distributed recharge estimates. Results show that estimated atrazine
      concentrations can be related to soil survey information. Areas with high
      potential vulnerability to atrazine leaching were found for soils with low
      organic carbon content and sandy loam and loam textures. Travel times for
      atrazine peak concentrations to the compliance depth ranged from 350 to 730 d.
      The extent of areas with estimated atrazine concentrations above the maximum
      contaminant level was less extensive when uniform annual recharge values were
      used. Simulated TTF concentrations were highest for eastern Fresno County, a
      vulnerability pattern that is also supported by field observations. The TTF
      modeling approach is shown to be a useful tool for quantitative pesticide
      leaching estimates at regional scales significantly larger than those of previous
      studies.

PMID- 15254132
TI  - Release of Cryptosporidium and Giardia from dairy cattle manure: physical
      factors.
AB  - Various physical factors affecting the release rate of naturally occurring
      Cryptosporidium parvum oocysts and Giardia duodenalis cysts from dairy manure
      disks to sprinkled water were studied. The investigated factors included
      temperature (5 or 23 degrees C), manure type (calf manure, a 50% calf and 50% cow
      manure mixture, and a 10% calf and 90% cow manure mixture), and water application
      method (mist or drip) and flow rate. Effluent concentrations of manure and
      (oo)cysts were always several orders of magnitude below their initial
      concentration in the manure, decreased gradually, and exhibited persistent
      concentration tailing. Release of manure and (oo)cysts were found to be related
      by a constant factor, the so-called release efficiency of (oo)cysts. A previously
      developed (oo)cyst release model that included these release efficiencies
      provided a satisfactory simulation of the observed release. An effect of
      temperature on the release of manure and (oo)cysts was not apparent. The manure
      and (oo)cyst release rates from cow manure decreased faster than those from calf
      manure, and (oo)cyst release efficiencies from cow manure were higher than those
      from calf manure. In comparison with mist application, dripping water resulted in
      higher release rates of manure and (oo)cysts and in higher (oo)cyst release
      efficiencies due to the increased mechanical forces associated with droplet
      impact. Mist application at a higher flow rate resulted in faster release, but
      did not affect the (oo)cyst release efficiencies. The data and modeling approach
      described herein provide insight and an enhanced ability to describe the
      influence of physical factors on (oo)cyst release.

PMID- 15254133
TI  - Nitrogen availability from composts for humid region perennial grass and legume
      grass forage production.
AB  - Perennial forages may be ideally suited for fertilization with slow N release
      amendments such as composts, but difficulties in predicting N supply from
      composts have limited their routine use in forage production. A field study was
      conducted to compare the yield and protein content of a binary legume-grass
      forage mixture and a grass monocrop cut twice annually, when fertilized with
      diverse composts. In all three years from 1998-2000, timothy (Phleum pratense L.)
      red clover (Trifolium pratense L.) and timothy swards were fertilized with
      ammonium nitrate (AN) at up to 150 and 300 kg N ha(-1) yr(-1), respectively.
      Organic amendments, applied at up to 600 kg N ha(-1) yr(-1) in the first two
      years only, included composts derived from crop residue (CSC), dairy manure
      (DMC), or sewage sludge (SSLC), plus liquid dairy manure (DM). Treatments DM at
      150 kg N ha(-1) yr(-1) and CSC at 600 kg N ha(-1) yr(-1) produced cumulative
      timothy yields matching those obtained for inorganic fertilizer. Apparent
      nitrogen recovery (ANR) ranged from 0.65% (SSLC) to 15.1% (DMC) for composts,
      compared with 29.4% (DM) and 36.5% (AN). The legume component (approximately 30%)
      of the binary mixture acted as an effective "N buffer" maintaining forage yield
      and protein content consistently higher, and within a narrower range, across all
      treatments. Integrating compost utilization into livestock systems that use
      legume-grass mixtures may reduce the risk of large excesses or deficits of N,
      moderate against potential losses in crop yield and quality, and by accommodating
      lower application rates of composts, reduce soil P and K accumulation.

PMID- 15254134
TI  - Phosphorus speciation in manure-amended alkaline soils.
AB  - Two common manure storage practices are stockpiles and lagoons. The manure from
      stockpiles is applied to soils in solid form, while lagoon manure is applied as a
      liquid. Soil amendment with manure in any form introduces a significant amount of
      phosphorus (P) that exists in both organic and inorganic forms. However, little
      is known about P speciation in manure stored under different conditions, or the
      subsequent forms when applied to soils. We used solution (31)P nuclear magnetic
      resonance (NMR) spectroscopy and conventional P fractionation and speciation
      methods to investigate P forms in dairy manure and liquid lagoon manure, and to
      study how long-term amendment with these manures influenced surface and
      subsurface soil P speciation. Our results show that the P forms in solid and
      lagoon manure are similar. About 30% of the total P was organic, mostly as
      orthophosphate monoesters. On a dry weight basis, total P was much higher in the
      solid manure. In the manure-amended soils the total P concentrations of the
      surface soils were similar, regardless of manure type. Total P in the subsurface
      soil was greater in the lagoon-manure-amended soil than the solid-manure-amended
      subsurface soil. However, the fraction of organic P was greater in the subsurface
      of the solid-manure-amended soil. The NMR results indicate that the majority of
      organic P in the soils is phytic acid, which is enriched in the surface soils
      compared with the subsurface soils. These results provide insight into P
      speciation and dynamics in manure-amended soils that will further increase our
      understanding on how best to manage manure disposal on soils.

PMID- 15254135
TI  - Phosphorus distribution in dairy manures.
AB  - The chemical composition of manure P is a key factor determining its potential
      bioavailability and susceptibility to runoff. The distribution of P forms in 13
      dairy manures was investigated with sequential fractionation coupled with
      orthophosphate-releasing enzymatic hydrolysis. Among the 13 dairy manures, manure
      total P varied between 4100 and 18,300 mg kg(-1) dry matter (DM). Water
      extractable P was the largest fraction, with inorganic phosphorus (P(i))
      accounting for 12 to 44% of manure total P (1400-6800 mg kg(-1)) and organic
      phosphorus (P(o)) for 2 to 23% (130-1660 mg kg(-1)), respectively. In the
      NaHCO(3) fraction, P(i) varied between 740 and 4200 mg P kg(-1) DM (4-44% of
      total manure P), and P(o) varied between 340 and 1550 mg P kg(-1) DM (2-27% of
      total manure P). In the NaOH fraction, P(i) fluctuated around 200 mg P kg(-1) DM,
      and P(o) ranged from 130 to 630 mg P kg(-1) DM. Of the enzymatically hydrolyzable
      P(o) in the three fractions, phytate-like P dominated, measuring 26 to 605 mg kg(
      1) DM, whereas monoester P and DNA-like P were relatively low and less variable.
      Although concentrations of various P forms varied considerably, significant
      correlations between manure total P and certain P forms were observed. For
      example, H(2)O-extracted P(i) was correlated with total manure P (R(2) = 0.62),
      and so was NaOH-extracted P(o) (R(2) = 0.81). Data also show that the amount of P
      released by a single extraction with sodium acetate (100 mM, pH 5.0) was
      equivalent to the sum of P in all three fractions (H(2)O-, NaHCO(3)-, and NaOH
      extractable P). Thus, a single extraction by sodium acetate buffer could provide
      an efficient evaluation of plant-available P in animal manure, while the
      sequential fractionation approach provides more detailed characterization of
      manure P.

PMID- 15254136
TI  - Phosphorus runoff from incorporated and surface-applied liquid swine manure and
      phosphorus fertilizer.
AB  - Excessive fertilization with organic and/or inorganic P amendments to cropland
      increases the potential risk of P loss to surface waters. The objective of this
      study was to evaluate the effects of soil test P level, source, and application
      method of P amendments on P in runoff following soybean [Glycine max (L.) Merr.].
      The treatments consisted of two rates of swine (Sus scrofa domestica) liquid
      manure surface-applied and injected, 54 kg P ha(-1) triple superphosphate (TSP)
      surface-applied and incorporated, and a control with and without chisel-plowing.
      Rainfall simulations were conducted one month (1MO) and six months (6MO) after P
      amendment application for 2 yr. Soil injection of swine manure compared with
      surface application resulted in runoff P concentration decreases of 93, 82, and
      94%, and P load decreases of 99, 94, and 99% for dissolved reactive phosphorus
      (DRP), total phosphorus (TP), and algal-available phosphorus (AAP), respectively.
      Incorporation of TSP also reduced P concentration in runoff significantly. Runoff
      P concentration and load from incorporated amendments did not differ from the
      control. Factors most strongly related to P in runoff from the incorporated
      treatments included Bray P1 soil extraction value for DRP concentration, and Bray
      P1 and sediment content in runoff for AAP and TP concentration and load.
      Injecting manure and chisel-plowing inorganic fertilizer reduced runoff P losses,
      decreased runoff volumes, and increased the time to runoff, thus minimizing the
      potential risk of surface water contamination. After incorporating the P
      amendments, controlling erosion is the main target to minimize TP losses from
      agricultural soils.

PMID- 15254137
TI  - Nitrogen and phosphorus flux rates from sediment in the lower St. Johns River
      estuary.
AB  - Internal cycling of nutrients from the sediment and water column can be an
      important contribution to the total nutrient load of an aquatic ecosystem. Our
      objective was to estimate the internal nutrient loading of the Lower St. Johns
      River (LSJR). Dissolved reactive phosphorus (DRP) and ammonium (NH(4)-N) flux
      from sediments were measured under aerobic and anaerobic water column conditions
      using intact cores, to estimate the overall contribution of the sediments to P
      and N loading to the LSJR. The DRP flux under aerobic water column conditions
      averaged 0.13 mg m(-2) d(-1), approximately 37 times lower than that under
      anaerobic conditions (4.77 mg m(-2) d(-1)). The average NH(4)-N released from the
      anaerobic cores (18.03 mg m(-2) d(-1)) was also significantly greater than in the
      aerobic cores for all sites and seasons, indicating the strong relationship
      between nutrient fluxes and oxygen availability in the water column. The mean
      annual internal DRP load was estimated to be 330 metric tons (Mg) yr(-1), 21% of
      the total P load to the river, while the mean annual internal load of NH(4)-N was
      determined to be 2066 Mg yr(-1), 28% of the total N load to the LSJR estuary. As
      water resource managers reduce external loading to the LSJR the frequency of
      anaerobic events should decline, thereby reducing nutrient fluxes from the
      sediment to the water column, reducing the internal loading of DRP and NH(4)-N.
      Results from this study demonstrate that the internal flux of nutrients from
      sediments may be a significant portion of the total load and should be accounted
      for in the total nutrient budget of the river for successful restoration.

PMID- 15254138
TI  - Analysis of volatile and semivolatile hydrocarbons recovered from steam
      classified municipal solid waste.
AB  - Hazardous household wastes comprise a significant proportion of municipal solid
      waste (MSW), and therefore serve as the source of many toxic or carcinogenic
      organic chemicals that are released in the environment through landfill gases or
      leachates. In the present study, we demonstrate the utility of the steam
      classification process in removing hazardous semivolatile organic compounds
      (SVOCs) and volatile organic compounds (VOCs) from MSW. Steam classification is a
      patented technology that involves the treatment of MSW with steam under pressure
      to yield a cellulosic biomass product that can be used as a fuel or in building
      materials. The SVOCs and VOCs from the waste off-gases are collected in the steam
      condensate and in an effluent charcoal filter. The results of this study show
      that at least two SVOCs and at least 17 VOCs can be removed from the waste. The
      most commonly identified compounds were diethylphthalate, styrene, 1,4
      dichlorobenzene, and toluene in the condensates, and styrene, 1,1,1
      trichloroethane, and toluene in the charcoal filters. On a weight basis, aromatic
      hydrocarbons were primarily recovered in the condensates, while the
      chloroaliphatic hydrocarbons were recovered almost exclusively from the charcoal
      filters. 1,3-Dichlorobenzene, 1,4-dichlorobenzene, and chloroform together
      comprised nearly 50% of the 4470 micrograms kg(-1) average mass of SVOCs and VOCs
      recovered from about 454 kg of MSW in these experiments. Toxicity characteristic
      leaching procedure (TCLP) analyses showed that steam classification recovered at
      least 75 to 91% of tested analytes. Overall, these results suggest that steam
      classification represents an effective technology for a significant reduction or
      the removal of hazardous organics from the waste stream, and, consequently, in
      reducing the extent of environmental contamination associated with landfill
      leachates and gases.

PMID- 15254139
TI  - Automated and continuous redox potential measurements in soil.
AB  - Redox potential (Eh) describes the electrical state of a matrix. In soils, Eh is
      an important parameter controlling the persistence of many organic and inorganic
      compounds. A popular, but also criticized, manual measuring method makes use of a
      small tip of Pt placed on a copper wire that is placed in the soil; a reference
      electrode is placed in the same soil at a fixed distance. Fluctuations in redox
      potential values measured in the soil can be very large and depth-dependent. This
      will be overlooked when making single-point measurements. We developed the
      datalogger Hypnos 2.0 for continuous redox potential and temperature measurements
      at various depths in the soil and without disturbance of the site. Hypnos is
      field-deployable, relatively cheap, and runs on batteries. The datalogger can use
      a "sleep mode" between sampling events. In sleep mode, there is no constant
      voltage on the Pt wire or the reference electrode, but there is only a short
      pulse during sampling. We did not measure an effect of this short pulse on the
      measured redox potential. In sandy soils in mesocosms and in a salt marsh soil we
      measured changes in the Eh as large as from -400 to +100 mV within 4 d, and daily
      cycles of 200 mV. Both absolute redox potential values and their diurnal
      variations were depth-dependent. Because single redox measurements are
      insufficient in describing redox conditions in some soil systems, Hypnos can be a
      powerful tool when studying the effects of fluctuating redox conditions on metal
      availability and pollutant degradation.

PMID- 15254140
TI  - Photodegradation of the endocrine-disrupting chemical 4-nonylphenol in biosolids
      applied to soil.
AB  - There is increasing concern about the environmental fate and impact of biosolids
      associated anthropogenic organic chemicals, among which 4-nonylphenol (4-NP) is
      one of the most studied chemicals. This is primarily because 4-NP is an endocrine
      disruptor and has been frequently detected in environmental samples. Due to its
      high hydrophobicity, 4-NP has high affinity for biosolids. Land application of 4
      NP-containing biosolids could potentially introduce large quantities of this
      chemical into the environment. A laboratory experiment was conducted to
      investigate the effect of artificial sunlight on 4-NP degradation in biosolids
      applied to soil. When exposed to artificial sunlight for 30 d, the top-5-mm layer
      of biosolids showed a 55% reduction of 4-NP, while less than 15% of the 4-NP was
      degraded when the biosolids were kept in the dark. Our results indicate that
      sensitized photolysis reaction plays an important role in reducing the levels of
      4-NP in land-applied biosolids. Surface application rather than soil
      incorporation of biosolids could be effective in reducing biosolids-associated
      organic chemicals that can be degraded through photolysis reactions. However, the
      risks of animal ingestion, foliar deposition, and runoff should also be evaluated
      when biosolids are applied on the soil surface.

PMID- 15254141
TI  - Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8
      triaza-spiro[4.5]decan-4-one] acts differently from nociceptin/orphanin FQ in rat
      periaqueductal gray slices.
AB  - Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8
      triaza-spiro[4.5]decan-4-one] was developed as a nonpeptide agonist of
      nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors, using bioassays at cloned
      receptors expressed in cell cultures. We have investigated the actions of Ro 64
      6198 at native NOP receptors of the ventrolateral periaqueductal gray (PAG), a
      crucial site for N/OFQ-induced reversal of opioid analgesia, using the patch
      clamp recording technique in rat brain slices. Ro 64-6198, like N/OFQ, activated
      G protein-coupled inwardly rectifying K(+) channels (GIRK) in ventrolateral PAG
      neurons but displayed only 60% efficacy and 22% potency of N/OFQ. Unlike N/OFQ
      that activated GIRK through NOP receptors in almost all tested neurons, Ro 64
      6198 affected only 62% (114/185) of the neurons recorded, among which 57% were
      sensitive to CompB (J-113397), a selective NOP receptor antagonist. The effect of
      Ro 64-6198 was not affected by naloxone (1 microM), sulpiride (10 microM), and [1
      (2-methoxyphenyl)-4-[4-2-phthalimido)butyl]piperazine (NAN-190) (1 microM),
      respectively, the antagonist of opioid, dopamine D(2), and 5-HT(1A) receptors. In
      Ro 64-6198-unresponsive neurons, N/OFQ activated GIRK through NOP receptors. It
      is concluded that Ro 64-6198 is a weak agonist of NOP receptors both in terms of
      potency and efficacy in ventrolateral PAG neurons. Heterogeneity of NOP receptors
      has been proposed from binding studies and in vivo functional studies. The
      possibility was discussed that two subsets of NOP receptors exist in
      ventrolateral PAG neurons, and Ro 64-6198 activates only one subset but N/OFQ
      activates both of them.

PMID- 15254142
TI  - Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake
      inhibitor in persistent pain models in rats.
AB  - 5-Hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) are implicated in
      modulating descending inhibitory pain pathways in the central nervous system.
      Duloxetine is a selective and potent dual 5-HT and NE reuptake inhibitor (SNRI).
      The ability of duloxetine to antagonize 5-HT depletion in para-chloramphetamine
      treated rats was comparable with that of paroxetine, a selective serotonin
      reuptake inhibitor (SSRI), whereas its ability to antagonize NE depletion in
      alpha-methyl-m-tyrosine-treated rats was similar to norepinephrine reuptake
      inhibitors (NRIs), thionisoxetine or desipramine. In this paradigm, duloxetine
      was also more potent than other SNRIs, including venlafaxine or milnacipran and
      amitriptyline. Low doses of the SSRI paroxetine or the NRI thionisoxetine alone
      did not have an effect on late phase paw-licking pain behavior in the formalin
      model of persistent pain; however, when combined, significantly attenuated this
      pain behavior. Duloxetine (3-15 mg/kg intraperitoneal) significantly attenuated
      late phase paw-licking behavior in a dose-dependent manner in the formalin model
      and was more potent than venlafaxine, milnacipran, and amitriptyline. These
      effects of duloxetine were evident at doses that did not cause neurologic
      deficits in the rotorod test. Duloxetine (5-30 mg/kg oral) was also more potent
      and efficacious than venlafaxine and milnacipran in reversing mechanical
      allodynia behavior in the L5/L6 spinal nerve ligation model of neuropathic pain.
      Duloxetine (3-30 mg/kg oral) was minimally efficacious in the tail-flick model of
      acute nociceptive pain. These data suggest that inhibition of both 5-HT and NE
      uptake may account for attenuation of persistent pain mechanisms. Thus,
      duloxetine may have utility in treatment of human persistent and neuropathic pain
      states.

PMID- 15254143
TI  - Interaction between ascorbate and light-exposed riboflavin induces lung
      remodeling.
AB  - Light-exposed parenteral multivitamins induce in lungs peroxide-like oxidant
      responses as well as the initiation of fibrosis. We hypothesized that peroxides
      generated in light-exposed total parenteral nutrition (TPN) affect lung
      remodeling. The objective was to assess the specific roles of peroxides,
      multivitamin preparation (MVP), and light exposure on lung remodeling during TPN.
      Three-day-old guinea pigs fitted with an indwelling catheter were assigned to the
      following intravenous regimens: TPN or MVP +/- photoprotection, H(2)O(2)+/-
      glutathione, MVP +/- metabisulfite, or ascorbic acid +/- riboflavin. Fed animals
      served as controls. After 4 days, lungs were sampled to determine alveolarization
      (intercepts), beta-actin mRNA (protection assay), and apoptosis (terminal
      deoxynucleotidyl transferase dUTP nick-end labeling). Data were analyzed by
      analysis of variance. The infusion of light-exposed multivitamins induced a 20%
      lower (p < 0.01) alveolarization index than fed controls, and 3-fold higher (p <
      0.01) apoptotic events. This was prevented by photoprotecting TPN. The effect of
      multivitamins on the alveolarization index was reproduced (p < 0.05) by infusion
      of light-exposed riboflavin in the presence of vitamin C. The alveolarization
      index correlated (r(2) = 0.35; p < 0.05) with beta-actin mRNA, suggesting
      alveolar disruption. Antiperoxides conferred no protection against decreased
      alveolarization. Lung remodeling induced by exposure of TPN to ambient light is
      not due to a direct effect of infused peroxides but rather to an interaction
      between vitamin C and peroxides generated by the exposure of riboflavin to light.
      It is speculated that this interaction may play a role in the development of
      chronic lung disease of premature infants who receive TPN and have immature
      antioxidant defenses.

PMID- 15254144
TI  - Bupropion (Zyban, Wellbutrin) inhibits nicotine-induced viral reactivation in
      herpes simplex virus type 1 latent rabbits.
AB  - We reported that nicotine applied via a transdermal patch (21 mg/day) induced
      viral reactivation and ocular shedding in herpes simplex virus type 1 (HSV-1)
      latent rabbits. One possible mechanism of action involves the release of
      catecholamines and other similar agents, triggering HSV reactivation. Bupropion
      (Zyban, Wellbutrin), a non-nicotine aid to smoking cessation, inhibits neuronal
      uptake of norepinephrine, serotonin, and dopamine. To determine whether bupropion
      inhibits HSV reactivation, rabbits latent with HSV-1 were grouped (at least 10
      rabbits/group) and treated as follows: nicotine patch (transdermal delivery) and
      bupropion [Zyban sustained-release tablets (150 mg) twice a day (oral)], nicotine
      patch only, Zyban tablets only [twice a day (oral)], nicotine patch with oral
      placebo [twice a day (oral)], or no drug treatment. Eyes were swabbed for 22
      consecutive days. The appearance of HSV-1 in the tear film was significantly less
      frequent in the bupropion-treated rabbits, in terms of positive rabbits/total
      rabbits, positive eyes/total eyes, and positive swabs/total swabs. Nicotine
      treated rabbits had 78/440 (17.7%) positive/total swabs, and nicotine/placebo
      treated rabbits had 149/792 (18.8%) positive/total swabs, whereas bupropion
      treated rabbits had 23/440 (5.2%), and nicotine/bupropion-treated rabbits had
      47/792 (5.9%) positive/total swabs. Thus, bupropion significantly reduces
      nicotine-induced HSV reactivation in latent rabbits.

PMID- 15254145
TI  - Inhibition of O6-methylguanine-DNA methyltransferase by glucose-conjugated
      inhibitors: comparison with nonconjugated inhibitors and effect on fotemustine
      and temozolomide-induced cell death.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is an
      important suicide enzyme involved in the defense against O(6)-alkylating
      mutagens. It also plays a role in the resistance of tumors to anticancer drugs
      targeting the O(6)-position of guanine, such as temozolomide and fotemustine.
      Several potent MGMT inhibitors have been developed sensitizing cells to O(6)
      alkylating agents. Aimed at targeting MGMT inhibitors to tumor cells, we
      synthesized MGMT inhibitory compounds conjugated with glucose to improve uptake
      in tumor cells. Here, we compared O(6)-benzylguanine, O(6)-2
      fluoropyridinylmethylguanine (O(6)FPG), O(6)-3-iodobenzylguanine, O(6)-4
      bromothenylguanine, and O(6)-5-iodothenylguanine with the corresponding C8-linker
      beta-d-glucose derivatives. All glucose conjugated inhibitors were 3- to 5-fold
      less effective than the corresponding nonconjugated drugs as to MGMT inhibition
      that was measured in cell extracts (in vitro) and cultivated HeLaS3 cells (in
      vivo). Except for O(6)FPG, IC(50) values of the guanine derivatives applied in
      vitro and in vivo were correlated. A similar correlation was not obvious for the
      corresponding glucosides, indicating differences in cellular uptake. C8-alpha-d
      glucosides were less effective than beta-glucosides. From the newly developed
      glucose-conjugated inhibitors tested, O(6)-4-bromothenylguanine-C8-beta-d
      glucoside (O(6)BTG-C8-betaGlu) was most potent in inhibiting MGMT both in vitro
      and in vivo. At a concentration of 0.1 microM, it inhibited cellular MGMT to
      completion. It was not toxic, even when applied chronically to cells at high dose
      (up to 20 microM). O(6)BTG-C8-betaGlu strongly potentiated the killing effect of
      fotemustine and temozolomide, causing reversal from MGMT+ to MGMT- phenotype.
      Therefore, O(6)BTG-C8-betaGlu seems to be especially suitable for approaching
      MGMT inhibitor targeting in tumor therapy.

PMID- 15254146
TI  - Interaction between dinucleotide and nicotinic receptors in individual
      cholinergic terminals.
AB  - Functional ionotropic nucleotidic receptors responding to diadenosine
      pentaphospate and nicotinic receptors responding to epibatidine coexpress in 19%
      of the total rat midbrain cholinergic terminals, as determined by the combination
      of immunological and microfluorimetric techniques. Activation of each independent
      receptor induces the intrasynaptosomal [Ca2+]i and acetylcholine (ACh) release in
      a dose-dependent way. The responses are inhibited by antagonists of the
      dinucleotide receptor and nicotinic receptors, thus confirming the involvement of
      specific receptors in both functions. Stimulation of single cholinergic terminal
      with both agonists altogether results in a significant decrease of the [Ca2+]i
      signaling compared with responses of each independent agonist. Inhibitory
      interaction between both receptors is reverted when one of them is blocked by
      specific antagonists, both in [Ca2+]i, and subsequent ACh release. The receptor's
      inhibitory cross talk confirm the involvement of calcium/calmodulin-dependent
      protein kinase II, CaMKII, as the inhibitory effects are reverted in the presence
      of the specific inhibitors KN-62 (2-[N-(4'-methoxybenzenesulfonyl)]-amino-N-(4'
      chlorophenyl)-2-propenyl-N-methylbenzylamine phosphate) and KN-93 (N-(2-[N-[4
      chlorocinnamyl]-N-methylaminomethyl]phenyl)-N-(2-hydroxyethyl)-4
      methoxybenzenesulphonamide). These results demonstrate the existence of an
      efficient interaction between these two channel populations, opening a new
      understanding of the functioning of the cholinergic synaptic terminals or
      terminals containing other neurotransmitters but exhibiting these receptor types
      or ones that are similar.

PMID- 15254147
TI  - Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like
      reaction in sensitized Guinea pigs.
AB  - Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in
      conditions associated with oxidative stress and inflammation. Because asthma is a
      chronic inflammatory disorder of the airways, we designed the present
      experimental study to evaluate the effects of PARP inhibition on allergen-induced
      asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in
      response to ovalbumin aerosol were absent in naive guinea pigs, whereas they
      became severe in the sensitized animals. In the latter ones, ovalbumin aerosol
      also induced a rapid increase in PARP activity, bronchiolar constriction,
      pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and
      nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in
      lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis
      factor-alpha in bronchoalveolar lavage fluid. Pretreatment with the PARP
      inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg
      b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the
      severity of cough and the occurrence of dyspnea and delayed the onset of
      respiratory abnormalities. Both PARP inhibitors were also able to prevent the
      above morphological and biochemical changes of lung tissue or bronchoalveolar
      lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the
      inactive analog of 3-aminobenzamide, had no effects.

PMID- 15254148
TI  - Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4
      and Nav1.5 in a rat model of critical illness myopathy.
AB  - Critical illness myopathy is a disorder in which skeletal muscle becomes
      electrically inexcitable. We previously demonstrated that a shift in the voltage
      dependence of fast inactivation of sodium currents contributes to inexcitability
      of affected fibres in an animal model of critical illness myopathy in which
      denervated rat skeletal muscle is treated with corticosteroids (steroid
      denervated; SD). In the current study we examined whether expression of Nav1.5
      contributes to the altered voltage dependence of sodium channel inactivation in
      SD muscle. We used TTX and mu-conotoxin GIIIB to selectively block Nav1.4 in SD
      muscle and found that the level of Nav1.5 did not correlate closely with the
      shift in fast inactivation. Surprisingly, we found that the voltage dependence of
      inactivation of Nav1.4 was similar to that of Nav1.5 in skeletal muscle in vivo.
      In severely affected fibres, inactivation of both Nav1.4 and Nav1.5 was shifted
      towards hyperpolarized potentials. We examined the role of denervation and
      steroid treatment in the shift of the voltage dependence of inactivation and
      found that both denervation and steroid treatment contribute to the shift in
      inactivation. Our results suggest that modulation of the voltage dependence of
      inactivation of both Nav1.4 and Nav1.5 in vivo contributes to loss of electrical
      excitability in SD muscle.

PMID- 15254149
TI  - Human TRPC5 channel activated by a multiplicity of signals in a single cell.
AB  - Here we explore the activation mechanisms of human TRPC5, a putative cationic
      channel that was cloned from a region of the X chromosome associated with mental
      retardation. No basal activity was evident but activity was induced by carbachol
      stimulation of muscarinic receptors independently of Ca2+ release. This is
      'receptor activation', as described for mouse TRPC5. In addition, and in the
      absence of receptor stimulation, extracellular gadolinium (0.1 mm) activated
      TRPC5, an effect that was mimicked by 5-20 mm extracellular Ca2+ with
      intracellular Ca2+ buffered. We refer to this as 'external ionic activation'.
      TRPC5 was also activated by modest elevation of [Ca2+]i in the absence of GTP-
      'calcium activation'. A putative fourth activation mechanism is a signal from
      depleted intracellular Ca2+ stores. Consistent with this idea, human TRPC5 was
      activated by a standard store-depletion/Ca2+ re-entry protocol, an effect that
      was difficult to explain by calcium activation. Multiplicity of TRPC5 activation
      was demonstrated in single cells and thus not dependent on heterogeneity of
      expression levels or cellular context. Therefore, human TRPC5 is activated by a
      range of stimuli, avoiding dependence on a single critical activator as in many
      other ion channels. One of these stimuli would seem to be a change in Ca2+
      handling by the endoplasmic reticulum.

PMID- 15254150
TI  - Cholinergic regulation of the evoked quantal release at frog neuromuscular
      junction.
AB  - The effects of cholinergic drugs on the quantal contents of the nerve-evoked
      endplate currents (EPCs) and the parameters of the time course of quantal release
      (minimal synaptic latency, main modal value of latency histogram and variability
      of synaptic latencies) were studied at proximal, central and distal regions of
      the frog neuromuscular synapse. Acetylcholine (ACh, 5 x 10(-4) M), carbachol
      (CCh, 1 x 10(-5) M) or nicotine (5 x 10(-6) M) increased the numbers of EPCs with
      long release latencies mainly in the distal region of the endplate (90-120 microm
      from the last node of Ranvier), where the synchronization of transmitter release
      was the most pronounced. The parameters of focally recorded motor nerve action
      potentials were not changed by either ACh or CCh. The effects of CCh and nicotine
      on quantal dispersion were reduced substantially by 5 x 10(-7) M (+)tubocurarine
      (TC). The muscarinic agonists, oxotremorine and the propargyl ester of
      arecaidine, as well as antagonists such as pirenzepine, AF-DX 116 and
      methoctramine, alone or in combination, did not affect the dispersion of the
      release. Muscarinic antagonists did not block the dispersion action of CCh.
      Cholinergic drugs either decreased the quantal content m(o) (muscarinic agonist,
      oxotremorine M, and nicotinic antagonist, TC), or decreased m(o) and dispersed
      the release (ACh, CCh and nicotine). The effects on m(o) were not related either
      to the endplate region or to the initial level of release dispersion. It follows
      that the mechanisms regulating the amount and the time course of transmitter
      release are different and that, among other factors, they are altered by
      presynaptic nicotinic receptors.

PMID- 15254151
TI  - Dendritically released transmitters cooperate via autocrine and retrograde
      actions to inhibit afferent excitation in rat brain.
AB  - Oxytocin is released from supraoptic magnocellular neurones and is thought to act
      at presynaptic receptors to inhibit transmitter release. We now show that this
      effect is mediated by endocannabinoids, but that oxytocin nonetheless plays an
      important role in endocannabinoid signalling. WIN55,212-2, a cannabinoid receptor
      agonist, mimicked the action of oxytocin and occluded oxytocin-induced
      presynaptic inhibition. The cannabinoid action is at the presynaptic terminal as
      shown by alteration in paired pulse ratio, a reduction in miniature EPSC
      frequency and immunohistochemical localization of CB1 receptors on presynaptic
      terminals. AM251, a CB1 receptor antagonist, blocked both the WIN55,212-2 and the
      oxytocin-induced presynaptic inhibition of EPSCs. Depolarization of postsynaptic
      magnocellular neurones (which contain fatty acid amide hydrolase, a cannabinoid
      catabolic enzyme) caused a transient inhibition of EPSCs that could be blocked by
      both the AM251 and Manning compound, an oxytocin/vasopressin receptor antagonist.
      This indicates that somatodendritic peptide release and action on previously
      identified autoreceptors facilitates the release of endocannabinoids that act as
      mediators of presynaptic inhibition.

PMID- 15254152
TI  - Elevated renal perfusion pressure does not contribute to natriuresis induced by
      isotonic saline infusion in freely moving dogs.
AB  - The study was designed to determine to what extent moderate elevation of renal
      perfusion pressure (RPP) via the mechanism of 'pressure natriuresis' contributes
      to the natriuresis induced by acute i.v. saline loading. Nine Beagle dogs
      maintained on ample sodium intake (5.5 mmol (kg body mass)(-1) day(-1)) were
      chronically equipped with an aortic occluder to servocontrol RPP, a bladder
      catheter to measure renal function, and catheters for measurement of RPP and mean
      arterial blood pressure (MABP). A swivel system allowed free movement in the
      kennel during experiments. Isotonic saline loading (500 ml in 100 min) was
      studied as follows: with and without servocontrol of RPP, and these two protocols
      repeated in the presence of angiotensin-converting enzyme inhibition (ACEI,
      Enalapril, 2 mg (kg body mass)(-1)). Saline loading increased MABP by about 12
      mmHg and sodium excretion from about 28 micromol min(-1) up to about 350 micromol
      min(-1). Without ACEI, servocontrol of RPP at 10% below control 24 h MABP
      slightly delayed the onset of the saline-induced natriuresis, but did not reduce
      peak sodium excretion or cumulative sodium excretion. The slight delay most
      probably resulted from pressure-controlled renin release because, with ACEI,
      servocontrol of RPP did not delay or reduce the saline-induced natriuresis. In
      conclusion, pressure natriuresis does not contribute to the natriuresis following
      acute saline loading.

PMID- 15254153
TI  - Spectral indices of human cerebral blood flow control: responses to augmented
      blood pressure oscillations.
AB  - We set out to fully examine the frequency domain relationship between arterial
      pressure and cerebral blood flow. Oscillatory lower body negative pressure
      (OLBNP) was used to create consistent blood pressure oscillations of varying
      frequency and amplitude to rigorously test for a frequency- and/or amplitude
      dependent relationship between arterial pressure and cerebral flow. We also
      examined the predictions from OLBNP data for the cerebral flow response to the
      stepwise drop in pressure subsequent to deflation of ischaemic thigh cuffs. We
      measured spectral powers, cross-spectral coherence, and transfer function gains
      and phases in arterial pressure and cerebral flow during three amplitudes (0, 20,
      and 40 mmHg) and three frequencies (0.10, 0.05, and 0.03 Hz) of OLBNP in nine
      healthy young volunteers. Pressure fluctuations were directly related to OLBNP
      amplitude and inversely to OLBNP frequency. Although cerebral flow oscillations
      were increased, they did not demonstrate the same frequency dependence seen in
      pressure oscillations. The overall pattern of the pressure-flow relation was of
      decreasing coherence and gain and increasing phase with decreasing frequency,
      characteristic of a high-pass filter. Coherence between pressure and flow was
      increased at all frequencies by OLBNP, but was still significantly lower at
      frequencies below 0.07 Hz despite the augmented pressure input. In addition,
      predictions of thigh cuff data from spectral estimates were extremely
      inconsistent and highly variable, suggesting that cerebral autoregulation is a
      frequency-dependent mechanism that may not be fully characterized by linear
      methods.

PMID- 15254154
TI  - Citrate transport in the human prostate epithelial PNT2-C2 cell line:
      electrophysiological analyses.
AB  - Although prostate synthesizes and releases large amounts of citrate, the
      mechanism of the release is not well understood. Most known citrate transporters
      mediate uptake of citrate from extracellular space and, consequently, are driven
      by the transmembrane Na+ gradient, which would not be appropriate for prostatic
      function. In the present study, we investigated citrate transport in a normal
      human prostate cell line, PNT2-C2, using mainly electrophysiological methods.
      Intracellular application of citrate through the patch pipette in the whole-cell
      recording mode induced an outward current whilst in response to extracellular
      citrate an inward current was recorded. Membrane currents induced by citrate were
      bigger than those elicited by other (equimolar) Krebs cycle intermediates. Both
      inward and outward citrate-induced currents had the same ionic dependence,
      inhibitor profile and reversal potential. In particular, the currents were
      strongly dependent on the transmembrane K+ gradient. Uptake and release of
      citrate and their K+ dependence were confirmed by spectrophotometric enzyme
      analyses. Citrate-induced membrane currents were also sensitive to pH, consistent
      with the transporter preferring the trivalent form. Application of intracellular
      Zn2+ generated an outward current which had the same quantitative K+ dependence
      as the citrate-induced currents. Extracellular application of a membrane-permeant
      Zn2+ chelator generated an inward current. These experiments suggested that m
      aconitase was tonically active in PNT2-C2 cells. Determination of 'forward' and
      'reverse' K+ stoichiometry both suggested a citrate: K+ ratio of 1: 4. We
      conclude that normal prostatic epithelial cells possess an electrogenic citrate
      transporter which mediates the cotransfer of 1 trivalent citrate anion alongside
      4 K+ out of cells and thus generates a net outward current.

PMID- 15254155
TI  - Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial
      node pacemaking.
AB  - The majority of Na+ channels in the heart are composed of the tetrodotoxin (TTX)
      resistant (KD, 2-6 microm) Nav1.5 isoform; however, recently it has been shown
      that TTX-sensitive (KD, 1-10 nm) neuronal Na+ channel isoforms (Nav1.1, Nav1.3
      and Nav1.6) are also present and functionally important in the myocytes of the
      ventricles and the sinoatrial (SA) node. In the present study, in mouse SA node
      pacemaker cells, we investigated Na+ currents under physiological conditions and
      the expression of cardiac and neuronal Na+ channel isoforms. We identified two
      distinct Na+ current components, TTX resistant and TTX sensitive. At 37 degrees
      C, TTX-resistant iNa and TTX-sensitive iNa started to activate at approximately 
      70 and approximately -60 mV, and peaked at -30 and -10 mV, with a current density
      of 22 +/- 3 and 18 +/- 1 pA pF(-1), respectively. TTX-sensitive iNa inactivated
      at more positive potentials as compared to TTX-resistant iNa. Using action
      potential clamp, TTX-sensitive iNa was observed to activate late during the
      pacemaker potential. Using immunocytochemistry and confocal microscopy, different
      distributions of the TTX-resistant cardiac isoform, Nav1.5, and the TTX-sensitive
      neuronal isoform, Nav1.1, were observed: Nav1.5 was absent from the centre of the
      SA node, but present in the periphery of the SA node, whereas Nav1.1 was present
      throughout the SA node. Nanomolar concentrations (10 or 100 nm) of TTX, which
      block TTX-sensitive iNa, slowed pacemaking in both intact SA node preparations
      and isolated SA node cells without a significant effect on SA node conduction. In
      contrast, micromolar concentrations (1-30 microm) of TTX, which block TTX
      resistant iNa as well as TTX-sensitive iNa, slowed both pacemaking and SA node
      conduction. It is concluded that two Na+ channel isoforms are important for the
      functioning of the SA node: neuronal (putative Nav1.1) and cardiac Nav1.5
      isoforms are involved in pacemaking, although the cardiac Nav1.5 isoform alone is
      involved in the propagation of the action potential from the SA node to the
      surrounding atrial muscle.

PMID- 15254156
TI  - Coexistence of gamma and high-frequency oscillations in rat medial entorhinal
      cortex in vitro.
AB  - High frequency oscillations (> 80-90 Hz) occur in neocortex and hippocampus in
      vivo where they are associated with specific behavioural states and more
      classical EEG frequency bands. In the hippocampus in vitro these oscillations can
      occur in the absence of pyramidal neuronal somatodendritic compartments and are
      temporally correlated with on-going, persistent gamma frequency oscillations.
      Their occurrence in the hippocampus is dependent on gap-junctional communication
      and it has been suggested that these high frequency oscillations originate as
      collective behaviour in populations of electrically coupled principal cell axonal
      compartments. Here we demonstrate that the superficial layers of medial
      entorhinal cortex can also generate high frequency oscillations associated with
      gamma rhythms. During persistent gamma frequency oscillations high frequency
      oscillations occur with a high bispectral coherence with the field gamma
      activity. Bursts of high frequency oscillations are temporally correlated with
      both the onset of compound excitatory postsynaptic potentials in fast-spiking
      interneurones and spikelet potentials in both pyramidal and stellate principal
      neurones. Both the gamma frequency and high frequency oscillations were
      attenuated by the gap junction blocker carbenoxolone. These data suggest that
      high frequency oscillations may represent the substrate for phasic drive to
      interneurones during persistent gamma oscillations in the medial entorhinal
      cortex.

PMID- 15254157
TI  - An amiloride-sensitive H+-gated Na+ channel in Caenorhabditis elegans body wall
      muscle cells.
AB  - About 30 genes are predicted to encode degenerin/epithelial sodium channels
      (DEG/ENaCs) in Caenorhabditis elegans but the gating mode of these channels has
      not been determined. Using the whole-cell configuration of the patch-clamp
      technique in acutely dissected C. elegans, we investigated the effects of H+ as a
      potential activating factor of DEG/ENaCs on electrical properties of body wall
      muscle cells. Under current-clamp conditions, decreasing external pH from 7.2 to
      6.1 led to a reversible depolarization of muscle cells associated with a decrease
      in input resistance which was partially inhibited by amiloride. Under voltage
      clamp conditions, extracellular acidification activated an inward desensitizing
      current at -60 mV. In the absence of external Ca2+, H+ -gated channels were found
      to be slightly more permeable to Na+ than to K+ and were blocked by amiloride
      with a K0.5 of 31 microm at -60 mV. An inward current could be also activated by
      protons in a GABA receptor null mutant in the presence of D-tubocurare and in an
      unc-105 null mutant. These results demonstrate that ion channels sharing common
      properties with mammalian acid-sensing ion channels (ASICs) are functional in C.
      elegans muscle which should prove useful for understanding proton sensing in
      animals.

PMID- 15254158
TI  - Severe acute respiratory syndrome coronavirus phylogeny: toward consensus.

PMID- 15254159
TI  - Innate sensing of viruses by toll-like receptors.

PMID- 15254160
TI  - Adeno-associated virus site-specific integration and AAVS1 disruption.
AB  - Adeno-associated virus (AAV) is a single-stranded DNA virus with a unique
      biphasic lifestyle consisting of both a productive and a latent phase. Typically,
      the productive phase requires coinfection with a helper virus, for instance
      adenovirus, while the latent phase dominates in healthy cells. In the latent
      state, AAV is found integrated site specifically into the host genome at
      chromosome 19q13.4 qtr (AAVS1), the only animal virus known to integrate in a
      defined location. In this study we investigated the latent phase of serotype 2
      AAV, focusing on three areas: AAV infection, rescue, and integration efficiency
      as a function of viral multiplicity of infection (MOI); efficiency of site
      specific integration; and disruption of the AAVS1 locus. As expected, increasing
      the AAV MOI resulted in an increase in the percentage of cells infected, with 80%
      of cells infected at an MOI of 10. Additional MOI only marginally effected a
      further increase in percentage of infected cells. In contrast to infection, we
      found very low levels of integration at MOIs of less than 10. At an MOI of 10, at
      which 80% of cells are infected, less than 5% of clonal cell lines contained
      integrated AAV DNA. At an MOI of 100 or greater, however, 35 to 40% of clonal
      cell lines contained integrated AAV DNA. Integration and the ability to rescue
      viral genomes were highly correlated. Analysis of integrated AAV indicated that
      essentially all integrants were AAVS1 site specific. Although maximal integration
      efficiency approached 40% of clonal cell lines (essentially 50% of infected
      cells), over 80% of cell lines contained a genomic disruption at the AAVS1
      integration locus on chromosome 19 ( approximately 100% of infected cells). Rep
      expression by itself and in the presence of a plasmid integration substrate was
      able to mediate this disruption of the AAVS1 site. We further characterized the
      disruption event and demonstrated that it resulted in amplification of the AAVS1
      locus. The data are consistent with a revised model of AAV integration that
      includes preliminary expansion of a defined region in AAVS1.

PMID- 15254161
TI  - Compartmentalization of human immunodeficiency virus type 1 between blood
      monocytes and CD4+ T cells during infection.
AB  - Distinct sequences of human immunodeficiency virus type 1 (HIV-1) have been found
      between different tissue compartments or subcompartments within a given tissue.
      Whether such compartmentalization of HIV-1 occurs between different cell
      populations is still unknown. Here we address this issue by comparing HIV-1
      sequences in the second constant region through the fifth hypervariable region
      (C2 to V5) of the surface envelope glycoprotein (Env) between viruses in purified
      blood CD14(+) monocytes and CD4(+) T cells obtained longitudinally from five
      infected patients over a time period ranging from 117 to 3,409 days
      postseroconversion. Viral populations in both cell types at early infection time
      points appeared relatively homogeneous. However, later in infections, all five
      patients showed heterogeneous populations in both CD14(+) monocytes and CD4(+) T
      cells. Three of the five patients had CD14(+) monocyte populations with
      significantly more genetic diversity than the CD4(+) T-cell population, while the
      other two patients had more genetic diversity in CD4(+) T cells. The cellular
      compartmentalization of HIV-1 between CD14(+) monocytes and CD4(+) T cells was
      not seen early during infections but was evident at the later time points for all
      five patients, indicating an association of viral compartmentalization with the
      time course of HIV-1 infection. The majority of HIV-1 V3 sequences indicated a
      macrophage-tropic phenotype, while a V3 sequence-predicted T-cell tropic virus
      was found in the CD4(+) T cells and CD14(+) monocytes of two patients. These
      findings suggest that HIV-1 in CD14(+) monocytes could disseminate and evolve
      independently from that in CD4(+) T cells over the course of HIV-1 infection,
      which may have implications on the development of new therapeutic strategies.

PMID- 15254162
TI  - Canine distemper virus and measles virus fusion glycoprotein trimers: partial
      membrane-proximal ectodomain cleavage enhances function.
AB  - The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin
      cleavage of the precursor F(0) into the F(1) and F(2) subunits. Here we show that
      an additional membrane-proximal cleavage occurs and modulates F protein function.
      We initially observed that the ectodomain of approximately one in three measles
      virus (MV) F proteins is cleaved proximal to the membrane. Processing occurs
      after cleavage activation of the precursor F(0) into the F(1) and F(2) subunits,
      producing F(1a) and F(1b) fragments that are incorporated in viral particles. We
      also detected the F(1b) fragment, including the transmembrane domain and
      cytoplasmic tail, in cells expressing the canine distemper virus (CDV) or mumps
      virus F protein. Six membrane-proximal amino acids are necessary for efficient
      CDV F(1a/b) cleavage. These six amino acids can be exchanged with the
      corresponding MV F protein residues of different sequence without compromising
      function. Thus, structural elements of different sequence are functionally
      exchangeable. Finally, we showed that the alteration of a block of membrane
      proximal amino acids results in diminished fusion activity in the context of a
      recombinant CDV. We envisage that selective loss of the membrane anchor in the
      external subunits of circularly arranged F protein trimers may disengage them
      from pulling the membrane centrifugally, thereby facilitating fusion pore
      formation.

PMID- 15254163
TI  - Adaptive mutations producing efficient replication of genotype 1a hepatitis C
      virus RNA in normal Huh7 cells.
AB  - Despite recent successes in generating subgenomic RNA replicons derived from
      genotype 1b strains of hepatitis C virus (HCV) that replicate efficiently in
      cultured cells, it has proven difficult to generate efficiently replicating RNAs
      from any other genotype of HCV. This includes genotype 1a, even though it is
      closely related to genotype 1b. We show here that an important restriction to
      replication of the genotype 1a H77c strain RNA in normal Huh7 cells resides
      within the amino-terminal 75 residues of the NS3 protease. We identified adaptive
      mutations located within this NS3 domain and within NS4A, in close proximity to
      the essential protease cofactor sequence, that act cooperative to substantially
      enhance the replication of this genotype 1a RNA in Huh7 cells. These and
      additional adaptive mutations, identified through a series of iterative
      transfections and the selection of G418-resistant cell clones, form two groups
      associating with distinct nonstructural protein domains: the NS3/4A protease and
      NS5A. A combination of mutations from both groups led to robust replication of
      otherwise unmodified H77c genomic RNA that was readily detectable by northern
      analysis within 4 days of transfection into Huh7 cells. We speculate that these
      adaptive mutations favorably influence assembly of the replicase complex with
      host cell-specific proteins, or alternatively promote interactions of NS3/4A
      and/or NS5A with cellular proteins involved in host cell antiviral defenses.

PMID- 15254164
TI  - A mouse-adapted enterovirus 71 strain causes neurological disease in mice after
      oral infection.
AB  - A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice,
      MP4, was generated after four serial passages of the parental EV71 strain 4643 in
      mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more
      cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced
      apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643
      in 1-day-old mice (50% lethal doses, 10(2) and 10(4) PFU/mouse, respectively).
      Strain MP4 (5 x 10(6) PFU/mouse), but not 4643, could orally infect 7-day-old
      mice, resulting in rear-limb paralysis followed by death 5 to 9 days after
      inoculation with the virus. Histopathologically, neuronal loss and apoptosis were
      evident in the spinal cords as well as the brain stems of the infected mice. The
      limb muscles displayed massive necrosis. There was early and transient virus
      replication in the intestines, whereas the spinal cord, brain, and muscle became
      the sites of viral replication during the late phase of the infection. Virus
      transmission occurred among infected and noninfected cagemates, as demonstrated
      by the occurrence of seroconversion and the presence of viable viruses in the
      stool samples of the latter. Protection against EV71 challenge was demonstrated
      following administration of hyperimmune serum 1 day after inoculation with the
      virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed
      four nucleotide changes on the 5' untranslated region, three on the VP2 region,
      and eight on the 2C region, resulting in one and four amino acid substitutions in
      the VP2 and 2C proteins, respectively.

PMID- 15254165
TI  - Superinfection exclusion in duck hepatitis B virus infection is mediated by the
      large surface antigen.
AB  - Superinfection exclusion is the phenomenon whereby a virus prevents the
      subsequent infection of an already infected host cell. The Pekin duck hepatitis B
      virus (DHBV) model was used to investigate superinfection exclusion in
      hepadnavirus infections. Superinfection exclusion was shown to occur both in vivo
      and in vitro with a genetically marked DHBV, DHBV-ClaI, which was unable to
      establish an infection in either DHBV-infected ducklings or DHBV-infected primary
      duck hepatocytes (PDHs). In addition, exclusion occurred in vivo even when the
      second virus had a replicative advantage. Superinfection exclusion appears to be
      restricted to DHBV, as adenovirus, herpes simplex virus type 1, and vesicular
      stomatitis virus were all capable of efficiently infecting DHBV-infected PDHs.
      Exclusion was dependent on gene expression by the original infecting virus, since
      UV-irradiated DHBV was unable to mediate the exclusion of DHBV-ClaI. Using
      recombinant adenoviruses expressing DHBV proteins, we determined that the large
      surface antigen mediated exclusion. The large surface antigen is known to cause
      down-regulation of a DHBV receptor, carboxypeptidase D (CPD). Receptor down
      regulation is a mechanism of superinfection exclusion seen in other viral
      infections, and so it was investigated as a possible mechanism of DHBV-mediated
      exclusion. However, a mutant large surface antigen which did not down-regulate
      CPD was still capable of inhibiting DHBV infection of PDHs. In addition,
      exclusion of DHBV-ClaI did not correlate with a decrease in CPD levels. Finally,
      virus binding assays and confocal microscopy analysis of infected PDHs indicated
      that the block in infection occurs after internalization of the second virus. We
      suggest that superinfection exclusion may result from the role of the L surface
      antigen as a regulator of intracellular trafficking.

PMID- 15254166
TI  - Inhibition of infectious pancreatic necrosis virus replication by atlantic salmon
      Mx1 protein.
AB  - Mx proteins form a family of interferon (IFN)-induced GTPases with potent
      antiviral activity against various single-stranded RNA viruses in mammals and
      chickens. In fish, alpha/beta IFN has been reported to inhibit the replication of
      infectious pancreatic necrosis virus (IPNV), but the mode of action has not been
      elucidated. A correlation between the inhibition of IPNV and Mx protein
      expression has, however, been observed. To examine whether Atlantic salmon Mx1
      protein (ASMx1) possesses antiviral activity against IPNV, CHSE-214 cells
      constitutively expressing ASMx1 were established. ASMx1 appeared to be localized
      in the cytoplasm. The ASMx1-expressing clone selected showed a severely reduced
      IPNV-induced cytopathic effect, which was confirmed by a 500-fold reduction in
      virus yield. The antiviral activity against IPNV was further confirmed by the
      inhibition of virus protein synthesis and the reduced accumulation of virus
      transcripts. The present work further adds to the body of evidence which suggests
      that antiviral activity is a major functional role of vertebrate Mx proteins.
      Moreover, the list of viruses inhibited by Mx proteins is extended to include
      double-stranded RNA viruses.

PMID- 15254167
TI  - Assembly of turnip yellow mosaic virus replication complexes: interaction between
      the proteinase and polymerase domains of the replication proteins.
AB  - Turnip yellow mosaic virus (TYMV), a positive-strand RNA virus in the alphavirus
      like supergroup, encodes two nonstructural replication proteins (140K and 66K),
      both of which are required for its RNA genome replication. The 140K protein
      contains domains indicative of methyltransferase, proteinase, and NTPase/helicase
      activities, while the 66K protein encompasses the RNA-dependent RNA polymerase
      domain. Recruitment of the 66K protein to the sites of viral replication, located
      at the periphery of chloroplasts, is dependent upon the expression of the 140K
      protein. Using antibodies raised against the 140K and 66K proteins and confocal
      microscopy, we report the colocalization of the TYMV replication proteins at the
      periphery of chloroplasts in transfected or infected cells. The replication
      proteins cofractionated in functional replication complexes or with purified
      chloroplast envelope membranes prepared from infected plants. Using a two-hybrid
      system and coimmunoprecipitation experiments, we also provide evidence for a
      physical interaction of the TYMV replication proteins. In contrast to what has
      been found for other members of the alphavirus-like supergroup, the interaction
      domains were mapped to the proteinase domain of the 140K protein and to a large
      region encompassing the core polymerase domain within the 66K protein.
      Coexpression and colocalization experiments confirmed that the helicase domain of
      the 140K protein is unnecessary for the proper recruitment of the 66K protein to
      the chloroplast envelope, while the proteinase domain appears to be essential for
      that process. These results support a novel model for the interaction of TYMV
      replication proteins and suggest that viruses in the alphavirus-like supergroup
      may have selected different pathways to assemble their replication complexes.

PMID- 15254168
TI  - Targeting of hepatitis C virus core protein to mitochondria through a novel C
      terminal localization motif.
AB  - The hepatitis C virus (HCV) core protein represents the first 191 amino acids of
      the viral precursor polyprotein and is cotranslationally inserted into the
      membrane of the endoplasmic reticulum (ER). Processing at position 179 by a
      recently identified intramembrane signal peptide peptidase leads to the
      generation and potential cytosolic release of a 179-amino-acid matured form of
      the core protein. Using confocal microscopy, we observed that a fraction of the
      mature core protein colocalized with mitochondrial markers in core-expressing
      HeLa cells and in Huh-7 cells containing the full-length HCV replicon.
      Subcellular fractionation confirmed this observation and showed that the core
      protein associates with purified mitochondrial fractions devoid of ER
      contaminants. The core protein also fractionated with mitochondrion-associated
      membranes, a site of physical contact between the ER and mitochondria. Using
      immunoelectron microscopy and in vitro mitochondrial import assays, we showed
      that the core protein is located on the mitochondrial outer membrane. A stretch
      of 10 amino acids within the hydrophobic C terminus of the processed core protein
      conferred mitochondrial localization when it was fused to green fluorescent
      protein. The location of the core protein in the outer mitochondrial membrane
      suggests that it could modulate apoptosis or lipid transfer, both of which are
      associated with this subcellular compartment, during HCV infection.

PMID- 15254169
TI  - Intracellular processing of human herpesvirus 6 glycoproteins Q1 and Q2 into
      tetrameric complexes expressed on the viral envelope.
AB  - Human herpesvirus 6 (HHV-6) glycoproteins H and L (gH and gL, respectively) and
      the 80-kDa form of glycoprotein Q (gQ-80K) form a heterotrimeric complex that is
      found on the viral envelope and that is a viral ligand for human CD46. Besides gQ
      80K, the gQ gene encodes an additional product whose mature molecular mass is 37
      kDa (gQ-37K) and which is derived from a different transcript. Therefore, we
      designated gQ-80K as gQ1 and gQ-37K as gQ2. We show here that gQ2 also interacts
      with the gH-gL-gQ1 complex in HHV-6-infected cells and in virions. To examine how
      these components interact in HHV-6-infected cells, we performed pulse-chase
      studies. The results demonstrated that gQ2-34K, which is endo-beta-N
      acetylglucosaminidase H sensitive and which is the precursor form of gQ2-37K,
      associates with gQ1-74K, which is the precursor form of gQ1-80K, within 30 min of
      the pulse period. After a 1-h chase, these precursor forms had associated with
      the gH-gL dimer. Interestingly, an anti-gH monoclonal antibody
      coimmunoprecipitated mainly gQ1-80K and gQ2-37K, with little gQ1-74K or gQ2-34K.
      These results indicate that although gQ2-34K and gQ1-74K interact in the
      endoplasmic reticulum, the gH-gL-gQ1-80K-gQ2-37K heterotetrameric complex arises
      in the post-endoplasmic reticulum compartment. The mature complex is subsequently
      incorporated into viral particles.

PMID- 15254170
TI  - Functional antagonism of chemokine receptor CCR1 reduces mortality in acute
      pneumovirus infection in vivo.
AB  - We present an antiviral-immunomodulatory therapeutic strategy involving the
      chemokine receptor antagonist Met-RANTES, which yields significant survival in
      the setting of an otherwise fatal respiratory virus infection. In previous work,
      we demonstrated that infection with the natural rodent pathogen pneumonia virus
      of mice involves robust virus replication accompanied by cellular inflammation
      modulated by the CC chemokine macrophage inflammatory protein 1alpha (MIP
      1alpha). We found that the antiviral agent ribavirin limited virus replication in
      vivo but had no impact on morbidity and mortality associated with this disease in
      the absence of immunomodulatory control. We show here that ribavirin reduces
      mortality, from 100% to 10 and 30%, respectively, in gene-deleted CCR1(-/-) mice
      and in wild-type mice treated with the small-molecule chemokine receptor
      antagonist, Met-RANTES. As MIP-1alpha-mediated inflammation is a common response
      to several distantly related respiratory virus pathogens, specific antiviral
      therapy in conjunction with blockade of the MIP-1alpha/CCR1 inflammatory cascade
      may ultimately prove to be a useful, generalized approach to severe respiratory
      virus infection and its pathological sequelae in human subjects.

PMID- 15254171
TI  - Transport of African swine fever virus from assembly sites to the plasma membrane
      is dependent on microtubules and conventional kinesin.
AB  - African swine fever virus (ASFV) is a large DNA virus that assembles in
      perinuclear viral factories located close to the microtubule organizing center.
      In this study, we have investigated the mechanism by which ASFV reaches the cell
      surface from the site of assembly. Immunofluorescence microscopy revealed that at
      16 h postinfection, mature virions were aligned along microtubules. Furthermore,
      virus movement to the cell periphery was inhibited when microtubules were
      depolymerized by nocodazole. In addition, ASFV infection resulted in the
      increased acetylation of microtubules as well as their protection against
      depolymerization by nocodazole. Immunofluorescence microscopy showed that
      conventional kinesin was recruited to virus factories and to a large fraction of
      virus particles in the cytoplasm. Consistent with a role for conventional kinesin
      during ASFV egress to the cell periphery, overexpression of the cargo-binding
      domain of the kinesin light chain severely inhibited the movement of particles to
      the plasma membrane. Based on our observations, we propose that ASFV is
      recognized as cargo by conventional kinesin and uses this plus-end microtubule
      motor to move from perinuclear assembly sites to the plasma membrane.

PMID- 15254172
TI  - Compartmentalization of VP16 in cells infected with recombinant herpes simplex
      virus expressing VP16-green fluorescent protein fusion proteins.
AB  - VP16 is an essential structural protein of herpes simplex virus. It plays
      important roles in immediate-early transcriptional regulation, in the modulation
      of the activities of other viral components, and in the pathway of assembly and
      egress of infectious virions. To gain further insight into the
      compartmentalization of this multifunctional protein we constructed and
      characterized recombinant viruses expressing VP16 linked to the green fluorescent
      protein (GFP). These viruses replicate with virtually normal kinetics and yields
      and incorporate the fusion protein into the virion, resulting in autofluorescent
      particles. De novo-synthesized VP16-GFP was first detected in a diffuse pattern
      within the nucleus. Nuclear VP16-GFP was progressively recruited to replication
      compartments, which coalesced into large globular domains. By 10 to 12 h after
      infection additional distinct foci containing VP16-GFP could be seen, almost
      exclusively located at the periphery of the replication compartments. At the same
      time pronounced accumulation was observed in the cytoplasm, first in a diffuse
      pattern and then accumulating in vesicle-like compartments which were
      concentrated in an asymmetric fashion reminiscent of the Golgi. Inhibition of DNA
      replication resulted in prolonged diffuse nuclear distribution with minimal
      cytoplasmic accumulation. Treatment with brefeldin disrupted the cytoplasm
      vesicular pattern, resulting in redistributed large foci. Time-lapse microscopy
      demonstrated various dynamic features of infection, including the active
      induction of very long cellular projections (up to 100 microM). Vesicular
      clusters containing VP16 were transported within projections to the termini,
      which developed bulbous ends and appeared to embed into the membranes of adjacent
      uninfected cells.

PMID- 15254173
TI  - Coexpression of UL20p and gK inhibits cell-cell fusion mediated by herpes simplex
      virus glycoproteins gD, gH-gL, and wild-type gB or an endocytosis-defective gB
      mutant and downmodulates their cell surface expression.
AB  - Syncytium formation in cells that express herpes simplex virus glycoprotein B
      (gB), gD, gH, and gL is blocked by gK (E. Avitabile, G. Lombardi, and G.
      Campadelli-Fiume, J. Virol. 77:6836-6844, 2003). Here, we report the results of
      two series of experiments. First, UL20 protein (UL20p) expression weakly
      inhibited cell-cell fusion. Coexpression of UL20p and gK drastically reduced
      fusion in a cell-line-dependent manner, with the highest inhibition in BHK cells.
      Singly expressed UL20p and gK localized at the endoplasmic reticulum and nuclear
      membranes. When they were coexpressed, both proteins relocalized to the Golgi
      apparatus. Remarkably, in cells that coexpressed UL20p and gK, the antifusion
      activity correlated with a downmodulation of gD, gB, gH, and gL cell surface
      expression. Second, gB(Delta867) has a partial deletion in the cytoplasmic tail
      that removed endocytosis motifs. Whereas wild-type (wt) gB was internalized in
      vesicles lined with the endosomal marker Rab5, gB(delta867) was not internalized,
      exhibited enhanced cell surface expression, and was more efficient in mediating
      cell-cell fusion than wt gB. The antifusion activity of UL20p and gK was also
      exerted when gB(delta867) replaced wt gB in the cell fusion assay. These studies
      show that the gB C tail carries a functional endocytosis motif(s) and that the
      removal of the motif correlated with increased gB surface expression and
      increased fusion activity. We conclude that cell-cell fusion in wt-virus-infected
      cells is negatively controlled by at least two mechanisms. The novel mechanism
      described here involves the concerted action of UL20p and gK and correlates with
      a moderate but consistent reduction in the cell surface expression of the fusion
      glycoproteins. This mechanism is independent of the one exerted through
      endocytosis-mediated downmodulation of gB from the plasma membrane.

PMID- 15254174
TI  - Comprehensive mutational analysis of a herpesvirus gene in the viral genome
      context reveals a region essential for virus replication.
AB  - Essential viral proteins perform vital functions during morphogenesis via a
      complex interaction with other viral and cellular gene products. Here, we present
      a novel approach to comprehensive mutagenesis of essential cytomegalovirus genes
      and biological analysis in the 230-kbp-genome context. A random Tn7-based
      mutagenesis procedure at the single-gene level was combined with site-specific
      recombination via the FLP/FLP recognition target site system for viral genome
      reconstitution. We show the function of more than 100 mutants from a larger
      library of M50/p35, a protein involved in capsid egress from the nucleus. This
      protein recruits other viral proteins and cellular enzymes to the inner nuclear
      membrane. Our approach enabled us to rapidly discriminate between essential and
      nonessential regions within the coding sequence. Based on the prediction of the
      screen, we were able to map a site essential for viral protein-protein
      interaction at the amino acid level.

PMID- 15254175
TI  - Degenerate in vitro genetic selection reveals mutations that diminish alfalfa
      mosaic virus RNA replication without affecting coat protein binding.
AB  - The alfalfa mosaic virus (AMV) RNAs are infectious only in the presence of the
      viral coat protein; however, the mechanisms describing coat protein's role during
      replication are disputed. We reasoned that mechanistic details might be revealed
      by identifying RNA mutations in the 3'-terminal coat protein binding domain that
      increased or decreased RNA replication without affecting coat protein binding.
      Degenerate (doped) in vitro genetic selection, based on a pool of randomized 39
      mers, was used to select 30 variant RNAs that bound coat protein with high
      affinity. AUGC sequences that are conserved among AMV and ilarvirus RNAs were
      among the invariant nucleotides in the selected RNAs. Five representative clones
      were analyzed in functional assays, revealing diminished viral RNA expression
      resulting from apparent defects in replication and/or translation. These data
      identify a set of mutations, including G-U wobble pairs and nucleotide mismatches
      in the 5' hairpin, which affect viral RNA functions without significant impact on
      coat protein binding. Because the mutations associated with diminished function
      were scattered over the 3'-terminal nucleotides, we considered the possibility
      that RNA conformational changes rather than disruption of a precise motif might
      limit activity. Native polyacrylamide gel electrophoresis experiments showed that
      the 3' RNA conformation was indeed altered by nucleotide substitutions. One
      interpretation of the data is that coat protein binding to the AUGC sequences
      determines the orientation of the 3' hairpins relative to one another, while
      local structural features within these hairpins are also critical determinants of
      functional activity.

PMID- 15254176
TI  - Cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in
      endothelial cells.
AB  - Endothelial cells have the ability to change their complement of cell surface
      proteins in response to inflammatory cytokines. We hypothesized that the
      expression of the coxsackievirus-adenovirus receptor (CAR), a viral receptor and
      putative cell-cell adhesion molecule, may be altered during the response of
      endothelial cells to inflammation. To test this hypothesis, we evaluated CAR
      protein and mRNA levels in human umbilical vein endothelial cells after they were
      exposed to tumor necrosis factor alpha, gamma interferon, or a combination of the
      two cytokines. Flow cytometric and Western blot analyses indicated that cytokine
      treatment led to a synergistic decrease in CAR protein expression. A Western blot
      analysis showed that CAR levels decreased to 16% +/- 4% or 1% +/- 4% of the CAR
      protein levels in untreated cells with either 24 or 48 h of cytokine treatment,
      respectively. Quantitative reverse transcription-PCR demonstrated that the
      combination treatment caused CAR mRNA levels to decrease to 21% +/- 12% or 5% +/-
      3% of the levels in untreated cells after a 24- or 48-h cytokine treatment,
      respectively. Reduced CAR expression led to a decrease in adenovirus (Ad) binding
      of 80% +/- 3% (compared with untreated endothelial cells), with a subsequent
      decrease in Ad-mediated gene transfer that was dependent on the dose and duration
      of cytokine treatment but not on the dose of Ad. A similar decrease in CAR
      protein level and susceptibility to Ad infection was observed in human
      microvascular endothelial cells, while CAR expression on normal human bronchial
      epithelial cells or A549 lung epithelial cells was less affected by cytokine
      treatments. Taken together, the data demonstrate that inflammatory cytokines
      decrease CAR mRNA and protein expression with a concomitant decrease in Ad
      binding, reflecting the impact of cell physiology on the function of CAR and the
      potential effect of inflammation on the ability of Ad to transfer genes to
      endothelial cells.

PMID- 15254177
TI  - Interactions between the inner and outer capsids of bluetongue virus.
AB  - Bluetongue virus is a large and structurally complex virus composed of three
      concentric capsid layers that surround 10 segments of a double-stranded RNA
      genome. X-ray crystallographic analysis of the particles without the outer capsid
      layer has provided atomic structural details of VP3 and VP7, which form the inner
      two layers. However, limited structural information is available on the other
      five proteins in the virion-two of which are important for receptor recognition,
      hemagglutination, and membrane interaction-are in the outer layer, and the
      others, important for endogenous transcriptase activity are internal. Here we
      report the electron cryomicroscopy (cryo-EM) reconstruction of the mature
      particle, which shows that the outer layer has a unique non-T = 13 icosahedral
      organization consisting of two distinct triskelion and globular motifs
      interacting extensively with the underlying T = 13 layer. Comparative cryo-EM
      analysis of the recombinant corelike particles has shown that VP1 (viral
      polymerase) and VP4 (capping enzyme) together form a flower-shaped structure
      attached to the underside of VP3, directly beneath the fivefold axis. The
      structural data have been substantiated by biochemical studies demonstrating the
      interactions between the individual outer and inner capsid proteins.

PMID- 15254178
TI  - Herpes simplex virus type 1 infection induces the stabilization of p53 in a USP7-
      and ATM-independent manner.
AB  - The major oncoprotein p53 regulates several cellular antiproliferation pathways
      that can be triggered in response to a variety of cellular stresses, including
      viral infection. The stabilization of p53 is a key factor in the ability of cells
      to initiate an efficient transcriptional response after cellular stress. Here we
      present data demonstrating that herpes simplex virus type 1 (HSV-1) infection of
      HFFF-2 cells, a low-passage-number nontransformed human primary cell line,
      results in the stabilization of p53. This process required viral immediate-early
      gene expression but occurred independently of the viral regulatory protein ICP0
      and viral DNA replication. No specific viral protein could be identified as being
      solely responsible for the effect, which appears to be a cellular response to
      developing HSV-1 infections. HSV-1 infection also induced the phosphorylation of
      p53 at residues Ser15 and Ser20, which have previously been implicated in its
      stabilization in response to DNA damage. However, an HSV-1 infection of ATM(-/-)
      cells, which lack a kinase implicated in these phosphorylation events, did not
      lead to the phosphorylation of p53 at these residues, but nonetheless p53 was
      stabilized. We also show that the wild-type p53 expressed by osteosarcoma U2OS
      cells can be stabilized in response to DNA damage induced by UV irradiation, but
      not in response to HSV-1 infection. These data suggest that multiple cellular
      mechanisms are initiated to stabilize p53 during an HSV-1 infection. These
      mechanisms occur independently of ICP0 and its ability to sequester USP7 and may
      differ from those initiated in response to DNA damage.

PMID- 15254179
TI  - Isolation of capsid protein dimers from the tick-borne encephalitis flavivirus
      and in vitro assembly of capsid-like particles.
AB  - Flaviviruses have a spherical capsid that is composed of multiple copies of a
      single capsid protein and, in contrast to the viral envelope, apparently does not
      have an icosahedral structure. So far, attempts to isolate distinct particulate
      capsids and soluble forms of the capsid protein from purified virions as well as
      to assemble capsid-like particles in vitro have been largely unsuccessful. Here
      we describe the isolation of nucleocapsids from tick-borne encephalitis (TBE)
      virus and their disintegration into a capsid protein dimer by high-salt
      treatment. Purified capsid protein dimers could be assembled in vitro into capsid
      like particles when combined with in vitro transcribed viral RNA. Particulate
      structures could also be obtained when single-stranded DNA oligonucleotides were
      used. These data suggest that the dimeric capsid protein functions as a basic
      building block in the assembly process of flaviviruses.

PMID- 15254180
TI  - Appearance of the bona fide spiral tubule of ORF virus is dependent on an intact
      10-kilodalton viral protein.
AB  - Parapoxviruses can be morphologically distinguished from other poxviruses in
      conventional negative staining electron microscopy (EM) by their ovoid appearance
      and the spiral tubule surrounding the virion's surface. However, this technique
      may introduce artifacts. We have examined Orf virus (ORFV; the prototype species
      of the Parapoxvirus genus) by cryoelectron microscopy (cryo-EM) and cryo-negative
      staining EM. From these studies we suggest that the shape and unique spiral
      tubule are authentic features of the parapoxviruses. We also constructed an ORFV
      mutant deleted of a gene encoding a 10-kDa protein, which is an orthologue of the
      vaccinia virus (VACV) 14-kDa fusion protein, and investigated its ultrastructure.
      This mutant virus multiplied slowly in permissive cells and produced infectious
      but morphologically aberrant particles. Mutant virions lacked the spiral tubule
      but displayed short disorganized tubules similar to those observed on the surface
      of VACV. In addition, thin extensions or loop-like structures were appended to
      the ORFV mutant particles. We suggest that these appended structures arise from a
      failure of the mutant virus particles to properly seal and that the sealing
      activity is dependent on the 10-kDa protein.

PMID- 15254181
TI  - Porcine arterivirus infection of alveolar macrophages is mediated by sialic acid
      on the virus.
AB  - Recently, we showed that porcine sialoadhesin (pSn) mediates internalization of
      the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) in
      alveolar macrophages (Vanderheijden et al., J. Virol. 77:8207-8215, 2003). In
      rodents and humans, sialoadhesin, or Siglec-1, has been described as a macrophage
      restricted molecule and to specifically bind sialic acid moieties. In the current
      study, we investigated whether pSn is a sialic acid binding protein and, whether
      so, whether this property is important for its function as a PRRSV receptor.
      Using untreated and neuraminidase-treated sheep erythrocytes, we showed that pSn
      binds sialic acid. Furthermore, pSn-specific monoclonal antibody 41D3, which
      blocks PRRSV infection, inhibited this interaction. PRRSV attachment to and
      infection of porcine alveolar macrophages (PAM) were both shown to be dependent
      on the presence of sialic acid on the virus: neuraminidase treatment of virus but
      not of PAM blocked infection and reduced attachment. Enzymatic removal of all N
      linked glycans on the virus with N-glycosidase F reduced PRRSV infection, while
      exclusive removal of nonsialylated N-linked glycans of the high-mannose type with
      endoglycosidase H had no significant effect. Free sialyllactose and sialic acid
      containing (neo)glycoproteins reduced infection, while lactose and
      (neo)glycoproteins devoid of sialic acids had no significant effect. Studies with
      linkage-specific neuraminidases and lectins indicated that alpha2-3- and alpha2-6
      linked sialic acids on the virion are important for PRRSV infection of PAM. From
      these results, we conclude that pSn is a sialic acid binding lectin and that
      interactions between sialic acid on the PRRS virion and pSn are essential for
      PRRSV infection of PAM.

PMID- 15254182
TI  - Regulation of relative abundance of arterivirus subgenomic mRNAs.
AB  - The subgenomic (sg) mRNAs of arteriviruses (order Nidovirales) form a 5'- and 3'
      coterminal nested set with the viral genome. Their 5' common leader sequence is
      derived from the genomic 5'-proximal region. Fusion of sg RNA leader and "body"
      segments involves a discontinuous transcription step. Presumably during minus
      strand synthesis, the nascent RNA strand is transferred from one site in the
      genomic template to another, a process guided by conserved transcription
      regulating sequences (TRSs) at these template sites. Subgenomic RNA species are
      produced in different but constant molar ratios, with the smallest RNAs usually
      being most abundant. Factors thought to influence sg RNA synthesis are size
      differences between sg RNA species, differences in sequence context between body
      TRSs, and the mutual influence (or competition) between strand transfer reactions
      occurring at different body TRSs. Using an Equine arteritis virus infectious cDNA
      clone, we investigated how body TRS activity affected sg RNA synthesis from
      neighboring body TRSs. Flanking sequences were standardized by head-to-tail
      insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of
      sg RNA abundance, progressively favoring smaller RNA species, was observed.
      Disruption of body TRS function by mutagenesis did not have a significant effect
      on the activity of other TRSs. However, deletion of body TRS-containing regions
      enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from
      downstream TRSs. The results of this study provide considerable support for the
      proposed discontinuous extension of minus-strand RNA synthesis as a crucial step
      in sg RNA synthesis.

PMID- 15254183
TI  - Human immunodeficiency virus type 1 infection induces cyclin T1 expression in
      macrophages.
AB  - The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for
      viral replication and activates RNA polymerase II transcriptional elongation
      through the association with a cellular protein kinase composed of Cdk9 and
      cyclin T1. Tat binds to this kinase complex through a direct protein-protein
      interaction with cyclin T1. Monocytes/macrophages are important targets of HIV-1
      infection, and previous work has shown that cyclin T1 but not Cdk9 protein
      expression is low in monocytes isolated from blood. While Cdk9 expression is
      expressed at a high level during monocyte differentiation to macrophages in
      vitro, cyclin T1 expression is induced during the first few days of
      differentiation and is shut off after 1 to 2 weeks. We show here that the shutoff
      of cyclin T1 expression in late-differentiated macrophages involves proteasome
      mediated proteolysis. We also show that cyclin T1 can be reinduced by a number of
      pathogen-associated molecular patterns that activate macrophages, indicating that
      up-regulation of cyclin T1 is part of an innate immune response. Furthermore, we
      found that HIV-1 infection early in macrophage differentiation results in
      sustained cyclin T1 expression, while infection at late times in differentiation
      results in the reinduction of cyclin T1. Expression of the viral Nef protein from
      an adenovirus vector suggests that Nef contributes to the HIV-1 induction of
      cyclin T1. These findings suggest that HIV-1 infection hijacks a component of the
      innate immune response in macrophages that results in enhancement rather than
      inhibition of viral replication.

PMID- 15254184
TI  - By inhibiting replication, the large hepatitis delta antigen can indirectly
      regulate amber/W editing and its own expression.
AB  - Hepatitis delta virus (HDV) expresses two essential proteins with distinct
      functions. The small hepatitis delta antigen (HDAg-S) is expressed throughout
      replication and is needed to promote that process. The large form (HDAg-L) is
      farnesylated, is expressed only at later times via RNA editing of the amber/W
      site, and is required for virion assembly. When HDAg-L is artificially expressed
      at the onset of replication, it strongly inhibits replication. However, there is
      controversy concerning whether HDAg-L expressed naturally at later times as a
      consequence of editing and replication can similarly inhibit replication. Here,
      by stabilizing the predicted secondary structure downstream from the amber/W
      site, a replication-competent HDV mutant that exhibited levels of editing higher
      than those of the wild type was created. This mutant expressed elevated levels of
      HDAg-L early during replication, and at later times, its replication aborted
      prematurely. No further increase in amber/W editing was observed following the
      cessation of replication, indicating that editing was coupled to replication. A
      mutation in HDAg-L and a farnesyl transferase inhibitor were both used to abolish
      the ability of HDAg-L to inhibit replication. Such treatments rescued the
      replication defect of the overediting mutant, and even higher levels of amber/W
      editing resulted. It was concluded that when expressed naturally during
      replication, HDAg-L is able to inhibit replication and thereby inhibit amber/W
      editing and its own synthesis. In addition, the structure adjacent to the amber/W
      site is suboptimal for editing, and this creates a window of time in which
      replication can occur in the absence of HDAg-L.

PMID- 15254185
TI  - Epitope mapping of the major capsid protein of type 2 porcine circovirus (PCV2)
      by using chimeric PCV1 and PCV2.
AB  - Type 2 porcine circovirus (PCV2) is associated with postweaning multisystemic
      wasting syndrome in pigs, whereas the genetically related type 1 PCV (PCV1) is
      nonpathogenic. In this study, seven monoclonal antibodies (MAbs) against PCV2
      ORF2 capsid protein were generated, biologically characterized, and subsequently
      used to map the antigenic sites of PCV2 capsid protein by using infectious PCV
      DNA clones containing PCV1/PCV2-ORF2 chimeras. The PCV1/PCV2-ORF2 chimeras were
      constructed by serial deletions of PCV2-ORF2 and replacement with the
      corresponding sequences of the PCV1-ORF2. The reactivities of chimeric PCV1/PCV2
      clones in transfected PK-15 cells with the seven MAbs were detected by an
      immunofluorescence assay (IFA). The chimera (r140) with a deletion of 47 amino
      acids at the N terminus of PCV2-ORF2 reacted strongly to all seven MAbs.
      Expanding the deletion of PCV2-ORF2 from residues 47 to 57 (r175) abolished the
      recognition of MAb 3B7, 3C11, 4A10, 6H2, or 8F6 to the chimera. Further deletion
      of PCV2-ORF2 to 62 residues disrupted the binding of this chimera to all seven
      MAbs. IFA reactivities with all MAbs were absent when residues 165 to 233 at the
      C terminus of PCV2-ORF2 was replaced with that of PCV1-ORF2. Extending the
      sequence of PCV2-ORF2 from residues 165 (r464) to 185 (r526), 200 (r588), or 224
      (r652) restored the ability of the three chimeras to react with MAbs 3C11, 6H2,
      9H7, and 12G3 but not with 8F6, 3B7, or 4A10. When the four amino acids at the C
      terminus of r588 were replaced with that of PCV2-ORF2, the resulting chimera
      (r588F) reacted with all seven MAbs. The results from this study suggest that
      these seven MAbs recognized at least five different but overlapping
      conformational epitopes within residues 47 to 63 and 165 to 200 and the last four
      amino acids at the C terminus of the PCV2 capsid protein.

PMID- 15254186
TI  - Role of nucleolin in human parainfluenza virus type 3 infection of human lung
      epithelial cells.
AB  - Human parainfluenza virus type 3 (HPIV-3) is an airborne pathogen that infects
      human lung epithelial cells from the apical (luminal) plasma membrane domain. In
      the present study, we have identified cell surface-expressed nucleolin as a
      cellular cofactor required for the efficient cellular entry of HPIV-3 into human
      lung epithelial A549 cells. Nucleolin was enriched on the apical cell surface
      domain of A549 cells, and HPIV-3 interacted with nucleolin during entry. The
      importance of nucleolin during HPIV-3 replication was borne out by the
      observation that HPIV-3 replication was significantly inhibited following (i).
      pretreatment of cells with antinucleolin antibodies and (ii). preincubation of
      HPIV-3 with purified nucleolin prior to its addition to the cells. Moreover, HPIV
      3 cellular internalization and attachment assays performed in the presence of
      antinucleolin antibodies and purified nucleolin revealed the requirement of
      nucleolin during HPIV-3 internalization but not during attachment. Thus, these
      results suggest that nucleolin expressed on the surfaces of human lung epithelial
      A549 cells plays an important role during HPIV-3 cellular entry.

PMID- 15254188
TI  - Calicivirus 3C-like proteinase inhibits cellular translation by cleavage of
      poly(A)-binding protein.
AB  - Caliciviruses are single-stranded RNA viruses that cause a wide range of diseases
      in both humans and animals, but little is known about the regulation of cellular
      translation during infection. We used two distinct calicivirus strains, MD145-12
      (genus Norovirus) and feline calicivirus (FCV) (genus Vesivirus), to investigate
      potential strategies used by the caliciviruses to inhibit cellular translation.
      Recombinant 3C-like proteinases (r3CL(pro)) from norovirus and FCV were found to
      cleave poly(A)-binding protein (PABP) in the absence of other viral proteins. The
      norovirus r3CL(pro) PABP cleavage products were indistinguishable from those
      generated by poliovirus (PV) 3C(pro) cleavage, while the FCV r3CL(pro) products
      differed due to cleavage at an alternate cleavage site 24 amino acids downstream
      of one of the PV 3C(pro) cleavage sites. All cleavages by calicivirus or PV
      proteases separated the C-terminal domain of PABP that binds translation factors
      eIF4B and eRF3 from the N-terminal RNA-binding domain of PABP. The effect of PABP
      cleavage by the norovirus r3CL(pro) was analyzed in HeLa cell translation
      extracts, and the presence of r3CL(pro) inhibited translation of both endogenous
      and exogenous mRNAs. Translation inhibition was poly(A) dependent, and
      replenishment of the extracts with PABP restored translation. Analysis of FCV
      infected feline kidney cells showed that the levels of de novo cellular protein
      synthesis decreased over time as virus-specific proteins accumulated, and
      cleavage of PABP occurred in virus-infected cells. Our data indicate that the
      calicivirus 3CL(pro), like PV 3C(pro), mediates the cleavage of PABP as part of
      its strategy to inhibit cellular translation. PABP cleavage may be a common
      mechanism among certain virus families to manipulate cellular translation.

PMID- 15254187
TI  - Structure and function of the 3' terminal six nucleotides of the west nile virus
      genome in viral replication.
AB  - Using a self-replicating reporting replicon of West Nile (WN) virus, we performed
      a mutagenesis analysis to define the structure and function of the 3'-terminal 6
      nucleotides (nt) (5'-GGAUCU(OH)-3') of the WN virus genome in viral replication.
      We show that mutations of nucleotide sequence or base pair structure of any of
      the 3'-terminal 6 nt do not significantly affect viral translation, but exert
      discrete effects on RNA replication. (i). The flavivirus-conserved terminal 3' U
      is optimal for WN virus replication. Replacement of the wild-type 3' U with a
      purine A or G resulted in a substantial reduction in RNA replication, with a
      complete reversion to the wild-type sequence. In contrast, replacement with a
      pyrimidine C resulted in a replication level similar to that of the 3' A or G
      mutants, with only partial reversion. (ii). The flavivirus-conserved 3'
      penultimate C and two upstream nucleotides (positions 78 and 79), which
      potentially base pair with the 3'-terminal CU(OH), are absolutely essential for
      viral replication. (iii). The base pair structures, but not the nucleotide
      sequences at the 3rd (U) and the 4th (A) positions, are critical for RNA
      replication. (iv). The nucleotide sequences of the 5th (G) position and its base
      pair nucleotide (C) are essential for viral replication. (v). Neither the
      sequence nor the base pair structure of the 6th nucleotide (G) is critical for WN
      virus replication. These results provide strong functional evidence for the
      existence of the 3' flavivirus-conserved RNA structure, which may function as
      contact sites for specific assembly of the replication complex or for efficient
      initiation of minus-sense RNA synthesis.

PMID- 15254189
TI  - Increased levels of Wee-1 kinase in G(2) are necessary for Vpr- and gamma
      irradiation-induced G(2) arrest.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the
      G(2)/M transition and subsequently apoptosis. Here we examined the potential
      involvement of Wee-1 in Vpr-induced G(2) arrest. Wee-1 is a cellular protein
      kinase that inhibits Cdc2 activity, thereby preventing cells from proceeding
      through mitosis. We previously showed that the levels of Wee-1 correlate with Vpr
      mediated apoptosis. Here, we demonstrate that Vpr-induced G(2) arrest correlated
      with delayed degradation of Wee-1 at G(2)/M. Experimental depletion of Wee-1 by a
      small interfering RNA directed to wee-1 mRNA alleviated Vpr-induced G(2) arrest
      and allowed apparently normal progression through M into G(1). Similar results
      were observed when cells were arrested at G(2) following gamma irradiation. Thus,
      Wee-1 is integrally involved as a key cellular regulatory protein in the signal
      transduction pathway for HIV-1 Vpr-induced cell cycle arrest.

PMID- 15254190
TI  - Analysis of splice variants of the immediate-early 1 region of human
      cytomegalovirus.
AB  - The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) produces
      multiple mRNAs through differential splicing and polyadenylation. Reverse
      transcriptase PCR was used to characterize transcripts from exons 1, 2, 3, and 4
      (immediate-early 1 [IE1]). The expected IE72 and IE19 mRNAs were detected, as
      well as two heretofore-uncharacterized transcripts designated IE17.5 and IE9. The
      IE72, IE19, and IE17.5 transcripts utilized the same 5'-splice site in exon 3.
      IE9 utilized a cryptic 5'-splice site within exon 3. The IE19, IE17.5, and IE9
      transcripts all used different 3'-splice sites within exon 4. These spliced
      species occur in infected human foreskin fibroblast (HFF) cells, with
      accumulation kinetics similar to those of IE72 mRNA. IE19 and IE9 RNAs were much
      more abundant than IE17.5 RNA. Transfection of CV-1 cells with cDNAs resulted in
      IE19 and IE17.5 proteins detectable by antibodies to either N-terminal or C
      terminal epitopes. No IE9 protein product has been detected. We have not been
      able to detect IE19, IE17.5, or IE9 proteins during infection of HFF, HEL, or
      U373MG cells. Failure to detect IE19 protein contrasts with a previous report (M.
      Shirakata, M. Terauchi, M. Ablikin, K. Imadome, K. Hirai, T. Aso, and Y.
      Yamanashi, J. Virol. 76:3158-3167, 2002) of IE19 protein expression in HCMV
      infected HEL cells. Our analysis suggests that an N-terminal breakdown product of
      IE72 may be mistaken for IE19. Expression of IE19 or IE17.5 from its respective
      cDNA results in repression of viral gene expression in infected cells. We
      speculate that expression of these proteins during infection may be restricted to
      specific conditions or cell types.

PMID- 15254191
TI  - Sequential roles of receptor binding and low pH in forming prehairpin and hairpin
      conformations of a retroviral envelope glycoprotein.
AB  - A general model has been proposed for the fusion mechanisms of class I viral
      fusion proteins. According to this model a metastable trimer, anchored in the
      viral membrane through its transmembrane domain, transits to a trimeric
      prehairpin intermediate, anchored at its opposite end in the target membrane
      through its fusion peptide. A subsequent refolding event creates a trimer of
      hairpins (often termed a six-helix bundle) in which the previously well-separated
      transmembrane domain and fusion peptide (and their attached membranes) are
      brought together, thereby driving membrane fusion. While there is ample
      biochemical and structural information on the trimer-of-hairpins conformation of
      class I viral fusion proteins, less is known about intermediate states between
      native metastable trimers and the final trimer of hairpins. In this study we
      analyzed conformational states of the transmembrane subunit (TM), the fusion
      subunit, of the Env glycoprotein of the subtype A avian sarcoma and leukosis
      virus (ASLV-A). By analyzing forms of EnvA TM on mildly denaturing sodium dodecyl
      sulfate gels we identified five conformational states of EnvA TM. Following
      interaction of virions with a soluble form of the ASLV-A receptor at 37 degrees
      C, the metastable form of EnvA TM (which migrates at 37 kDa) transits to a 70-kDa
      and then to a 150-kDa species. Following subsequent exposure to a low pH (or an
      elevated temperature or the fusion promoting agent chlorpromazine), an additional
      set of bands at >150 kDa, and then a final band at 100 kDa, forms. Both an EnvA C
      helix peptide (which inhibits virus fusion and infectivity) and the fusion
      inhibitory agent lysophosphatidylcholine inhibit the formation of the >150- and
      100-kDa bands. Our data are consistent with the 70- and 150-kDa bands
      representing precursor and fully formed prehairpin conformations of EnvA TM. Our
      data are also consistent with the >150-kDa bands representing higher-order
      oligomers of EnvA TM and with the 100-kDa band representing the fully formed six
      helix bundle. In addition to resolving fusion-relevant conformational
      intermediates of EnvA TM, our data are compatible with a model in which the EnvA
      protein is activated by its receptor (at neutral pH and a temperature greater
      than or equal to room temperature) to form prehairpin conformations of EnvA TM,
      and in which subsequent exposure to a low pH is required to stabilize the final
      six-helix bundle, which drives a later stage of fusion.

PMID- 15254193
TI  - Characterization of the murine alpha interferon gene family.
AB  - Mouse and human genomes carry more than a dozen genes coding for closely related
      alpha interferon (IFN-alpha) subtypes. IFN-alpha, as well as IFN-beta, IFN-kappa,
      IFN-epsilon, and limitin, are thought to bind the same receptor, raising the
      question of whether different IFN subtypes possess specific functions. As some
      confusion existed in the identity and characteristics of mouse IFN-alpha
      subtypes, the availability of data from the mouse genome sequence prompted us to
      characterize the murine IFN-alpha family. A total of 14 IFN-alpha genes were
      detected in the mouse genome, in addition to three IFN-alpha pseudogenes. Four
      IFN-alpha genes (IFN-alpha1, IFN-alpha7/10, IFN-alpha8/6, and IFN-alpha11)
      exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN
      alpha subtypes were found to be stable at pH 2 and to exhibit antiviral activity.
      Interestingly, some IFN subtypes (IFN-alpha4, IFN-alpha11, IFN-alpha12, IFN-beta,
      and limitin) showed higher biological activity levels than others, whereas IFN
      alpha7/10 exhibited lower activity. Most murine IFN-alpha turned out to be N
      glycosylated. However, no correlation was found between N-glycosylation and
      activity. The various IFN-alpha subtypes displayed a good correlation between
      their antiviral and antiproliferative potencies, suggesting that IFN-alpha
      subtypes did not diverge primarily to acquire specific biological activities but
      probably evolved to acquire specific expression patterns. In L929 cells, IFN
      genes activated in response to poly(I*C) transfection or to viral infection were,
      however, similar.

PMID- 15254192
TI  - Oral immunization with recombinant listeria monocytogenes controls virus load
      after vaginal challenge with feline immunodeficiency virus.
AB  - Recombinant Listeria monocytogenes has many attractive characteristics as a
      vaccine vector against human immunodeficiency virus (HIV). Wild-type and
      attenuated Listeria strains expressing HIV Gag have been shown to induce long
      lived mucosal and systemic T-cell responses in mice. Using the feline
      immunodeficiency virus (FIV) model of HIV we evaluated recombinant L.
      monocytogenes in a challenge system. Five cats were immunized with recombinant L.
      monocytogenes that expresses the FIV Gag and delivers an FIV Env-expressing DNA
      vaccine (LMgag/pND14-Lc-env). Control cats were either sham immunized or
      immunized with wild-type L. monocytogenes (LM-wt). At 1 year after vaginal
      challenge, provirus could not be detected in any of the nine tissues evaluated
      from cats immunized with the recombinant bacteria but was detected in at least
      one tissue in 8 of 10 control animals. Virus was isolated from bone marrow of
      four of five LMgag/pND14-Lc-env-immunized cats by use of a stringent coculture
      system but required CD8(+) T-cell depletion, indicating CD8(+) T-cell suppression
      of virus replication. Control animals had an inverted CD4:CD8 ratio in mesenteric
      lymph node and were depleted of both CD4(+) and CD8(+) intestinal epithelial T
      cells, while LMgag/pND14-Lc-env-immunized animals showed no such abnormalities.
      Vaginal FIV-specific immunoglobulin A was present at high titer in three
      LMgag/pND14-Lc-env-immunized cats before challenge and in all five at 1 year
      postchallenge. This study demonstrates that recombinant L. monocytogenes
      conferred some control of viral load after vaginal challenge with FIV.

PMID- 15254194
TI  - Progression or resolution of coxsackievirus B4-induced pancreatitis: a genomic
      analysis.
AB  - Group B coxsackieviruses are associated with chronic inflammatory diseases of the
      pancreas, heart, and central nervous system. Chronic pancreatitis, which can
      develop from acute pancreatitis, is considered a premalignant disorder because it
      is a major risk factor for pancreatic cancer. To explore the genetic events
      underlying the progression of acute to chronic disease, a comparative analysis of
      global gene expression during coxsackievirus B4-induced acute and chronic
      pancreatitis was undertaken. A key feature of acute pancreatitis that resolved
      was tissue regeneration, which was accompanied by increased expression of genes
      involved in cell growth, inhibition of apoptosis, and embryogenesis and by
      increased division of acinar cells. Acute pancreatitis that progressed to chronic
      pancreatitis was characterized by lack of tissue repair, and the expression map
      highlighted genes involved in apoptosis, acinoductular metaplasia, remodeling of
      the extracellular matrix, and fibrosis. Furthermore, immune responses appeared
      skewed toward development of alternatively activated (M2) macrophages and T
      helper 2 (Th2) cells during disease that resolved and toward classically
      activated (M1) macrophages and Th1 cells during disease that progressed. Our
      hypothesis is that growth and differentiation signals coupled with the M2/Th2
      milieu favor acinar cell proliferation, while diminished growth signals and the
      M1/Th1 milieu favor apoptosis of acinar cells and remodeling/proliferation of the
      extracellular matrix, resulting in fibrosis.

PMID- 15254195
TI  - APOBEC3G targets specific virus species.
AB  - Human APOBEC3G (huAPOBEC3G), also known as CEM15, is a broad antiretroviral host
      factor that deaminates dC to dU in the minus strand DNA of human immunodeficiency
      virus type 1 (HIV-1), other lentiviruses, and murine leukemia virus (MLV),
      thereby creating G-to-A hypermutation in the plus strand DNA to inhibit the
      infectivity of these viruses. In this study, we examined the antiretroviral
      function of a murine homologue of APOBEC3G (muAPOBEC3G) on several retrovirus
      systems with different producer cells. MuAPOBEC3G did not suppress the
      infectivity of murine retroviral vectors produced from human or murine cells,
      whereas it showed antiviral activity on both wild-type and Deltavif virions of
      HIV-1 in human cells. In contrast, huAPOBEC3G showed broad antiviral activity on
      HIV-1 and murine retroviral vectors produced from human cells as well as murine
      cells. These data suggested that muAPOBEC3G does not possess antiretroviral
      activity on murine retroviruses and has a different target specificity from that
      of huAPOBEC3G and that huAPOBEC3G works as a broad antiviral factor not only in
      human cells but also in murine cells. A functional interaction study between
      human and murine APOBEC3G supported the former hypothesis. Furthermore, studies
      on the expression of APOBEC3G in producer cells and its incorporation into
      virions revealed that muAPOBEC3G is incorporated into HIV-1 virions but not into
      MLV virions. Thus, muAPOBEC3G cannot suppress the infectivity of murine
      retrovirus because it is not incorporated into virions. We suggest that murine
      retroviruses can replicate in murine target cells expressing muAPOBEC3G because
      they are not targets for this enzyme.

PMID- 15254196
TI  - p53 targets simian virus 40 large T antigen for acetylation by CBP.
AB  - Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor
      p53 and the transcriptional coactivators CBP and p300. Binding of these cellular
      proteins in a ternary complex has been implicated in T Ag-mediated
      transformation. It has been suggested that the ability of CBP/p300 to modulate
      p53 function underlies p53's regulation of cell proliferation and tumorigenesis.
      In this study, we provide further evidence that CBP activity may be mediated
      through its synergistic action with p53. We demonstrate that SV40 T Ag is
      acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely
      mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53
      and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag
      to the C-terminal lysine residue 697. This acetylation site is conserved between
      the T antigens of the human polyomaviruses JC and BK, which are also known to
      interact with p53. We show that both JC and BK T antigens are also acetylated at
      corresponding sites in vivo. While other proteins are known to be acetylated by
      CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may
      provide a regulatory mechanism for T Ag binding to a cellular factor or play a
      role in another aspect of T Ag function.

PMID- 15254197
TI  - Purification of the cucumber necrosis virus replicase from yeast cells: role of
      coexpressed viral RNA in stimulation of replicase activity.
AB  - Purified recombinant viral replicases are useful for studying the mechanism of
      viral RNA replication in vitro. In this work, we obtained a highly active
      template-dependent replicase complex for Cucumber necrosis tombusvirus (CNV),
      which is a plus-stranded RNA virus, from Saccharomyces cerevisiae. The
      recombinant CNV replicase showed properties similar to those of the plant-derived
      CNV replicase (P. D. Nagy and J. Pogany, Virology 276:279-288, 2000), including
      the ability (i). to initiate cRNA synthesis de novo on both plus- and minus
      stranded templates, (ii). to generate replicase products that are shorter than
      full length by internal initiation, and (iii). to perform primer extension from
      the 3' end of the template. We also found that isolation of functional replicase
      required the coexpression of the CNV p92 RNA-dependent RNA polymerase and the
      auxiliary p33 protein in yeast. Moreover, coexpression of a viral RNA template
      with the replicase proteins in yeast increased the activity of the purified CNV
      replicase by 40-fold, suggesting that the viral RNA might promote the assembly of
      the replicase complex and/or that the RNA increases the stability of the
      replicase. In summary, this paper reports the first purified recombinant
      tombusvirus replicase showing high activity and template dependence, a finding
      that will greatly facilitate future studies on RNA replication in vitro.

PMID- 15254198
TI  - Recovery of human metapneumovirus genetic lineages a and B from cloned cDNA.
AB  - Human metapneumovirus (hMPV) is a newly discovered pathogen associated with
      respiratory tract illness, primarily in young children, immunocompromised
      individuals, and the elderly. The genomic sequence of the prototype hMPV isolate
      NL/1/00 without the terminal leader and trailer sequences has been reported
      previously. Here we describe the leader and trailer sequences of two hMPV
      isolates, NL/1/00 and NL/1/99, representing the two main genetic lineages of
      hMPV. Minigenome constructs in which the green fluorescent protein or
      chloramphenicol acetyltransferase genes are flanked by the viral genomic ends
      derived from both hMPV lineages and transcribed using a T7 RNA polymerase
      promoter-terminator cassette were generated. Cotransfection of minigenome
      constructs with plasmids expressing the polymerase complex components L, P, N,
      and M2.1 in 293T or baby hamster kidney cells resulted in expression of the
      reporter genes. When the minigenome was replaced by a sense or antisense full
      length cDNA copy of the NL/1/00 or NL/1/99 viral genomes, recombinant virus was
      recovered from transfected cells. Viral titers up to 10(7.2) and 10(5.7) 50%
      tissue culture infective dose/ml were achieved with the sense and antisense
      plasmids, respectively. The recombinant viruses replicated with kinetics similar
      to those of the parental viruses in Vero cells. This reverse genetics system
      provides an important new tool for applied and fundamental research.

PMID- 15254199
TI  - Common E protein determinants for attenuation of glycosaminoglycan-binding
      variants of Japanese encephalitis and West Nile viruses.
AB  - Natural isolates and laboratory strains of West Nile virus (WNV) and Japanese
      encephalitis virus (JEV) were attenuated for neuroinvasiveness in mouse models
      for flavivirus encephalitis by serial passage in human adenocarcinoma (SW13)
      cells. The passage variants displayed a small-plaque phenotype, augmented
      affinity for heparin-Sepharose, and a marked increase in specific infectivity for
      SW13 cells relative to the respective parental viruses, while the specific
      infectivity for Vero cells was not altered. Therefore, host cell adaptation of
      passage variants was most likely a consequence of altered receptor usage for
      virus attachment-entry with the involvement of cell surface glycosaminoglycans
      (GAG) in this process. In vivo blood clearance kinetics of the passage variants
      was markedly faster and viremia was reduced relative to the parental viruses,
      suggesting that affinity for GAG (ubiquitously present on cell surfaces and
      extracellular matrices) is a key determinant for the neuroinvasiveness of
      encephalitic flaviviruses. A difference in pathogenesis between WNV and JEV,
      which was reflected in more efficient growth in the spleen and liver of the WNV
      parent and passage variants, accounted for a less pronounced loss of
      neuroinvasiveness of GAG binding variants of WNV than JEV. Single gain-of-net
      positive-charge amino acid changes at E protein residue 49, 138, 306, or 389/390,
      putatively positioned in two clusters on the virion surface, define molecular
      determinants for GAG binding and concomitant virulence attenuation that are
      shared by the JEV serotype flaviviruses.

PMID- 15254200
TI  - Trimeric hantavirus nucleocapsid protein binds specifically to the viral RNA
      panhandle.
AB  - Hantaviruses are tripartite negative-sense RNA viruses and members of the
      Bunyaviridae family. The nucleocapsid (N) protein is encoded by the smallest of
      the three genome segments (S). N protein is the principal structural component of
      the viral capsid and is central to the hantavirus replication cycle. We examined
      intermolecular N-protein interaction and RNA binding by using bacterially
      expressed Sin Nombre virus N protein. N assembles into di- and trimeric forms.
      The mono- and dimeric forms exist transiently and assemble into a trimeric form.
      In contrast, the trimer is highly stable and does not efficiently disassemble
      into the mono- and dimeric forms. The purified N-protein trimer is able to
      discriminate between viral and nonviral RNA molecules and, interestingly,
      recognizes and binds with high affinity the panhandle structure composed of the
      3' and 5' ends of the genomic RNA. In contrast, the mono- and dimeric forms of N
      bind RNA to form a complex that is semispecific and salt sensitive. We suggest
      that trimerization of N protein is a molecular switch to generate a protein
      complex that can discriminate between viral and nonviral RNA molecules during the
      early steps of the encapsidation process.

PMID- 15254201
TI  - Itinerary of hepatitis B viruses: delineation of restriction points critical for
      infectious entry.
AB  - Little is known about cellular determinants essential for human hepatitis B virus
      infection. Using the duck hepatitis B virus as a model, we first established a
      sensitive binding assay for both virions and subviral particles and subsequently
      elucidated the characteristics of the early viral entry steps. The infection
      itinerary was found to initiate with the attachment of viral particles to a low
      number of binding sites on hepatocytes (about 10(4) per cell). Virus
      internalization was fully accomplished in less than 3 h but was then followed by
      a period of unprecedented length, about 14 h, until completion of nuclear import
      of the viral genome. Steps subsequent to virus entry depended on both intact
      microtubules and their dynamic turnover but not on actin cytoskeleton. Notably,
      cytoplasmic trafficking of viral particles and emergence of nuclear covalently
      closed circular DNA requires microtubules during entry only at and for specific
      time periods. Taken together, these data disclose for the first time a series of
      steps and their kinetics that are essential for the entry of hepatitis B viruses
      into hepatocytes and are different from those of any other virus reported so far.

PMID- 15254202
TI  - Dileucine and YXXL motifs in the cytoplasmic tail of the bovine leukemia virus
      transmembrane envelope protein affect protein expression on the cell surface.
AB  - Several retroviruses downmodulate the cell surface expression of envelope (Env)
      proteins through peptide sequences located in the cytoplasmic tail of the
      transmembrane (TM) subunit. We investigated whether cell surface expression of a
      chimeric protein containing the cytoplasmic domain of the TM protein (CTM) of
      bovine leukemia virus (BLV) was regulated by two membrane-proximal dileucine
      motifs or by tyrosine Y487 or Y498 in YXXL motifs. A chimeric protein composed of
      the extracellular and membrane-spanning portions of human CD8-alpha plus a wild
      type (wt) BLV CTM was detectable on the surface of only 40% of the cells in which
      it was transiently expressed. Replacement of either dileucine pair with alanines
      increased the level of surface display of chimeric proteins. Nearly all cells
      became surface positive when both dileucine motifs were altered simultaneously
      and when either an N-terminal segment containing both dileucine motifs or a C
      terminal segment containing all YXXL motifs was deleted. In contrast, replacement
      of Y487 or Y498 with alanine or phenylalanine enabled only small increases in
      surface display compared with wt levels. Chimeric proteins had similar
      stabilities but were downmodulated from the cell surface at three different
      rates. Point mutants segregated into each of the three groups of proteins
      categorized according to these different rates. Interestingly, Y487 mutants were
      downmodulated less efficiently than Y498 mutants, which behaved like wt. CD8-CTM
      chimeric proteins were phosphorylated on serine residues, but the native BLV Env
      protein was not phosphorylated either in transfected cells or in a lymphoid cell
      line constitutively producing BLV. Thus, both dileucine and YXXL motifs within
      the BLV CTM contribute to downmodulation of a protein containing this domain.
      Interactions with other proteins may influence surface exposure of Env protein
      complexes in virus-infected cells, assisting in viral evasion of adaptive
      immunity.

PMID- 15254203
TI  - Role of CD8+ T cells in control of West Nile virus infection.
AB  - Infection with West Nile virus (WNV) causes fatal encephalitis more frequently in
      immunocompromised humans than in those with a healthy immune system. Although a
      complete understanding of this increased risk remains unclear, experiments with
      mice have begun to define how different components of the adaptive and innate
      immune response function to limit infection. Previously, we demonstrated that
      components of humoral immunity, particularly immunoglobulin M (IgM) and IgG, have
      critical roles in preventing dissemination of WNV infection to the central
      nervous system. In this study, we addressed the function of CD8(+) T cells in
      controlling WNV infection. Mice that lacked CD8(+) T cells or classical class Ia
      major histocompatibility complex (MHC) antigens had higher central nervous system
      viral burdens and increased mortality rates after infection with a low-passage
      number WNV isolate. In contrast, an absence of CD8(+) T cells had no effect on
      the qualitative or quantitative antibody response and did not alter the kinetics
      or magnitude of viremia. In the subset of CD8(+)-T-cell-deficient mice that
      survived initial WNV challenge, infectious virus was recovered from central
      nervous system compartments for several weeks. Primary or memory CD8(+) T cells
      that were generated in vivo efficiently killed target cells that displayed WNV
      antigens in a class I MHC-restricted manner. Collectively, our experiments
      suggest that, while specific antibody is responsible for terminating viremia,
      CD8(+) T cells have an important function in clearing infection from tissues and
      preventing viral persistence.

PMID- 15254204
TI  - Hepatitis C virus targets DC-SIGN and L-SIGN to escape lysosomal degradation.
AB  - Hepatitis C virus (HCV) is a major health problem. However, the mechanism of
      hepatocyte infection is largely unknown. We demonstrate that the dendritic cell
      (DC)-specific C-type lectin DC-SIGN and its liver-expressed homologue L-SIGN/DC
      SIGNR are important receptors for HCV envelope glycoproteins E1 and E2.
      Mutagenesis analyses demonstrated that both HCV E1 and E2 bind the same binding
      site on DC-SIGN as the pathogens human immunodeficiency virus type 1 (HIV-1) and
      mycobacteria, which is distinct from the cellular ligand ICAM-3. HCV virus-like
      particles are efficiently captured and internalized by DCs through binding of DC
      SIGN. Antibodies against DC-SIGN specifically block HCV capture by both immature
      and mature DCs, demonstrating that DC-SIGN is the major receptor on DCs.
      Interestingly, internalized HCV virus-like particles were targeted to
      nonlysosomal compartments within immature DCs, where they are protected from
      lysosomal degradation in a manner similar to that demonstrated for HIV-1. Lewis X
      antigen, another ligand of DC-SIGN, was internalized to lysosomes, demonstrating
      that the internalization pathway of DC-SIGN-captured ligands may depend on the
      structure of the ligand. Our results suggest that HCV may target DC-SIGN to
      "hide" within DCs and facilitate viral dissemination. L-SIGN, expressed by THP-1
      cells, internalized HCV particles into similar nonlysosomal compartments,
      suggesting that L-SIGN on liver sinusoidal endothelial cells may capture HCV from
      blood and transmit it to hepatocytes, the primary target for HCV. We therefore
      conclude that both DCs and liver sinusoidal endothelial cells may act as
      reservoirs for HCV and that the C-type lectins DC-SIGN and L-SIGN, as important
      HCV receptors, may represent a molecular target for clinical intervention in HCV
      infection.

PMID- 15254205
TI  - Coiled-coil domains in glycoproteins B and H are involved in human
      cytomegalovirus membrane fusion.
AB  - Human cytomegalovirus (CMV) utilizes a complex route of entry into cells that
      involves multiple interactions between viral envelope proteins and cellular
      receptors. Three conserved viral glycoproteins, gB, gH, and gL, are required for
      CMV-mediated membrane fusion, but little is known of how these proteins cooperate
      during entry (E. R. Kinzler and T. Compton, submitted for publication). The goal
      of this study was to begin defining the molecular mechanisms that underlie
      membrane fusion mediated by herpesviruses. We identified heptad repeat sequences
      predicted to form alpha-helical coiled coils in two glycoproteins required for
      fusion, gB and gH. Peptides derived from gB and gH containing the heptad repeat
      sequences inhibited virus entry when introduced coincident with virus inoculation
      onto cells or when mixed with virus prior to inoculation. Neither peptide
      affected binding of CMV to fibroblasts, suggesting that the peptides inhibit
      membrane fusion. Both gB and gH coiled-coil peptides blocked entry of several
      laboratory-adapted and clinical strains of human CMV, but neither peptide
      affected entry of murine CMV or herpes simplex virus type 1 (HSV-1). Although
      murine CMV and HSV-1 gB and gH have heptad repeat regions, the ability of human
      CMV gB and gH peptides to inhibit virus entry correlates with the specific
      residues that comprise the heptad repeat region. The ability of gB and gH coiled
      coil peptides to inhibit virus entry independently of cell contact suggests that
      the coiled-coil regions of gB and gH function differently from those of class I,
      single-component fusion proteins. Taken together, these data support a critical
      role for alpha-helical coiled coils in gB and gH in the entry pathway of CMV.

PMID- 15254206
TI  - Induction of mucosal and systemic neutralizing antibodies against human
      immunodeficiency virus type 1 (HIV-1) by oral immunization with bovine
      Papillomavirus-HIV-1 gp41 chimeric virus-like particles.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope-specific neutralizing
      antibodies are generated late after initial infection, and the neutralizing
      antibody response is weak in the infected individuals. Administration of
      neutralizing antibodies such as 2F5 to HIV-1-infected individuals resulted in
      reductions in viral loads. Because HIV-1 is transmitted mainly via mucosa and
      because HIV-specific neutralizing antibodies reduce HIV-1 in infected
      individuals, a vaccine that can induce both mucosal and systemic HIV-1-specific
      neutralizing antibodies may be used to prevent and to treat HIV-1 infection. In
      this study, we made a bovine papillomavirus (BPV) L1-HIV-1 gp41 fusion protein in
      which ELDKWA of gp41 was inserted into the N terminus of BPV L1 (amino acids 130
      to 136). Expression of the fusion protein in insect cells led to the assembly of
      chimeric virus-like particles (CVLPs). The CVLPs had sizes similar to those of
      BPV particles and were able to bind to the cell surface and penetrate the cell
      membrane. Oral immunization of mice with CVLPs induced gp41-specific serum
      immunoglobulin G (IgG) and intestinal secretory IgA. However, intramuscular
      immunization with the CVLPs resulted in similar amounts of gp41-specific IgG but
      low levels of secretory IgA. The antibodies specifically recognized the fixed HIV
      1 gp41 on the cell surface. Importantly, the sera and fecal extracts from mice
      orally immunized with the CVLPs neutralized HIV-1(MN) in vitro. Thus, BPV-HIV-1
      gp41 CVLPs may be used to prevent and to treat HIV-1 infection.

PMID- 15254207
TI  - Global identification of three major genotypes of varicella-zoster virus:
      longitudinal clustering and strategies for genotyping.
AB  - By analysis of a single, variable, and short DNA sequence of 447 bp located
      within open reading frame 22 (ORF22), we discriminated three major varicella
      zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that
      showed nearly complete homology to ORF22 of the European reference strain Dumas
      were assigned to the European (E) genotype. All Japanese isolates, defined as the
      Japanese (J) genotype, were identical in the respective genomic region and proved
      the most divergent from the E strains, carrying four distinct variations. The
      remaining isolates carried a combination of E- and J-specific variations in the
      target sequence and thus were collectively termed the mosaic (M) genotype. Three
      hundred twenty-six isolates collected in 27 countries were genotyped. A
      distinctive longitudinal distribution of VZV genotypes supports this approach.
      Among 111 isolates collected from European patients, 96.4% were genotype E.
      Consistent with this observation, approximately 80% of the VZV strains from the
      United States were also genotype E. Similarly, genotype E viruses were dominant
      in the Asian part of Russia and in eastern Australia. M genotype viruses were
      strongly dominant in tropical regions of Africa, Indochina, and Central America,
      and they were common in western Australia. However, genotype M viruses were also
      identified as a minority in several countries worldwide. Two major intertypic
      variations of genotype M strains were identified, suggesting that the M genotype
      can be further differentiated into subgenotypes. These data highlight the
      direction for future VZV genotyping efforts. This approach provides the first
      simple genotyping method for VZV strains in clinical samples.

PMID- 15254208
TI  - Inhibition of infection and replication of human herpesvirus 8 in microvascular
      endothelial cells by alpha interferon and phosphonoformic acid.
AB  - Infection of endothelial cells with human herpesvirus 8 (HHV-8) is an essential
      event in the development of Kaposi's sarcoma. When primary microvascular
      endothelial cells (MECs) were infected with HHV-8 at a low multiplicity of
      infection, considerable latent replication of HHV-8 occurred, leading to a time
      dependent increase in the percentage of virus-infected cells that was accompanied
      by cellular spindling and growth to a high density with loss of contact
      inhibition. Only a low percentage of MECs supported lytic replication of HHV-8
      and produced infectious virus. Phosphonoformic acid blocked production of
      infectious virus but did not inhibit the rapid expansion of latently infected
      MECs. Pretreatment of MECs with alpha interferon (IFN-alpha) prior to infection
      effectively reduced HHV-8 viral gene expression, latent replication, and
      production of infectious virus. High levels of the double-stranded RNA activated
      protein kinase (PKR) were expressed in HHV-8-infected cells, and incubation with
      IFN-alpha increased PKR expression more in virus-infected cells than in
      uninfected cells. MECs that were immortalized with simian virus 40 large-T
      antigen differed from nonimmortalized MECs in their response to infection with
      HHV-8 and demonstrated that cells with elevated levels of expression of antiviral
      transcripts expressed viral transcripts at reduced levels. These studies
      demonstrate that MECs respond to HHV-8 with enhanced expression of cellular
      antiviral genes and that augmentation of innate antiviral defenses with IFN-alpha
      is a more effective strategy than inhibition of viral lytic replication to
      protect MECs from infection with HHV-8 and to restrict proliferation of virus
      infected MECs.

PMID- 15254209
TI  - Effect of vaccine use in the evolution of Mexican lineage H5N2 avian influenza
      virus.
AB  - An outbreak of avian influenza (AI) caused by a low-pathogenic H5N2 type A
      influenza virus began in Mexico in 1993 and several highly pathogenic strains of
      the virus emerged in 1994-1995. The highly pathogenic virus has not been reported
      since 1996, but the low-pathogenic virus remains endemic in Mexico and has spread
      to two adjacent countries, Guatemala and El Salvador. Measures implemented to
      control the outbreak and eradicate the virus in Mexico have included a widespread
      vaccination program in effect since 1995. Because this is the first case of long
      term use of AI vaccines in poultry, the Mexican lineage virus presented us with a
      unique opportunity to examine the evolution of type A influenza virus circulating
      in poultry populations where there was elevated herd immunity due to maternal and
      active immunity. We analyzed the coding sequence of the HA1 subunit and the NS
      gene of 52 Mexican lineage viruses that were isolated between 1993 and 2002.
      Phylogenetic analysis indicated the presence of multiple sublineages of Mexican
      lineage isolates at the time vaccine was introduced. Further, most of the viruses
      isolated after the introduction of vaccine belonged to sublineages separate from
      the vaccine's sublineage. Serologic analysis using hemagglutination inhibition
      and virus neutralization tests showed major antigenic differences among isolates
      belonging to the different sublineages. Vaccine protection studies further
      confirmed the in vitro serologic results indicating that commercial vaccine was
      not able to prevent virus shedding when chickens were challenged with
      antigenically different isolates. These findings indicate that multilineage
      antigenic drift, which has not been observed in AI virus, is occurring in the
      Mexican lineage AI viruses and the persistence of the virus in the field is
      likely aided by its large antigenic difference from the vaccine strain.

PMID- 15254210
TI  - Human cytomegalovirus-encoded G protein-coupled receptor US28 mediates smooth
      muscle cell migration through Galpha12.
AB  - Coupling of G proteins to ligand-engaged chemokine receptors is the paramount
      event in G-protein-coupled receptor signal transduction. Previously, we have
      demonstrated that the human cytomegalovirus-encoded chemokine receptor US28
      mediates human vascular smooth muscle cell (SMC) migration in response to either
      RANTES or monocyte chemoattractant protein 1. In this report, we identify the G
      proteins that couple with US28 to promote vascular SMC migration and identify
      other signaling molecules that play critical roles in this process. US28-mediated
      cellular migration was enhanced with the expression of the G-protein subunits
      Galpha12 and Galpha13, suggesting that US28 may functionally couple to these G
      proteins. In correlation with this observation, US28 was able to activate RhoA, a
      downstream effector of Galpha12 and Galpha13 in cell types with these G proteins
      but not in those without them and activation of RhoA was dependent on US28
      stimulation with RANTES. In addition, inactivation of RhoA or the RhoA-associated
      kinase p160ROCK with a dominant-negative mutant of RhoA or the small molecule
      inhibitor Y27632, respectively, abrogated US28-induced SMC migration. The data
      presented here suggest that US28 functionally signals through Galpha12 family G
      proteins and RhoA in a ligand-dependent manner and these signaling molecules are
      important for the ability of US28 to induce cellular migration.

PMID- 15254211
TI  - Disparate regions of envelope protein regulate syncytium formation versus
      spongiform encephalopathy in neurological disease induced by murine leukemia
      virus TR.
AB  - The murine leukemia virus (MLV) TR1.3 provides an excellent model to study the
      wide range of retrovirus-induced central nervous system (CNS) pathology and
      disease. TR1.3 rapidly induces thrombotic events in brain microvessels and causes
      cell-specific syncytium formation of brain capillary endothelial cells (BCEC). A
      single amino acid substitution, W102G, in the MLV envelope protein (Env)
      regulates the pathogenic effects. The role of Env in determining this disease
      phenotype compared to the induction of spongiform encephalomyelitis with a longer
      latency, as seen in several other MLV and in human retroviruses, was determined
      by studying in vitro-attenuated TR1.3. Virus cloned from this selection, termed
      TRM, induced progressive neurological disease characterized by ataxia and
      paralysis and the appearance of spongiform neurodegeneration throughout the brain
      stem and spinal cord. This disease was associated with virus replication in both
      BCEC and highly ramified glial cells. TRM did not induce syncytium formation,
      either in vivo or in vitro. Sequence and mutational analyses demonstrated that
      TRM contained a reversion of Env G102W but that neurological disease mapped to
      the single amino acid substitution Env S159P. The results demonstrate that single
      nucleotide changes within disparate regions of Env control dramatically different
      CNS disease patterns.

PMID- 15254212
TI  - The virion host shutoff protein of herpes simplex virus type 1 has RNA
      degradation activity in primary neurons.
AB  - The virion host shutoff protein (Vhs) of herpes simplex virus type 1 induces
      destabilization of mRNA following infection. Our study of primary neurons from CD
      1 mice demonstrates that vhs is functional in neurons but that more Vhs is
      required to mediate RNA degradation in neurons than in other susceptible cells.

PMID- 15254213
TI  - Epstein-Barr virus latent membrane protein 1 (LMP-1) half-life in epithelial
      cells is down-regulated by lytic LMP-1.
AB  - This study examined the effect of naturally occurring Epstein-Barr virus (EBV)
      latent membrane protein 1 (LMP-1) gene sequence variation on the LMP-1 half-life
      in epithelial cells. The LMP-1 half-life was not influenced by sequence variation
      in amino acids 250 to 307 or amino acids 343 to 352. The LMP-1 half-life was
      short when the amino acid encoded at position 129 was methionine, the initiation
      codon product of lytic LMP-1 (lyLMP-1). The mutation of amino acid 129 to
      isoleucine greatly increased the LMP-1 half-life. Expression of lyLMP-1 in trans
      down-regulated the LMP-1 half-life in a dose-dependent manner and restored a
      short-half-life phenotype to the mutated LMP-1 construct lacking the cis ability
      to express lyLMP-1. This observed dominant negative effect of lyLMP-1 expression
      on the LMP-1 half-life in epithelial cells in vitro may have implications for EBV
      epithelial oncogenesis in vivo.

PMID- 15254214
TI  - Synaptic plasticity and translation initiation.
AB  - It is widely accepted that protein synthesis, including local protein synthesis
      at synapses, is required for several forms of synaptic plasticity. Local protein
      synthesis enables synapses to control synaptic strength independent of the cell
      body via rapid protein production from pre-existing mRNA. Therefore, regulation
      of translation initiation is likely to be intimately involved in modulating
      synaptic strength. Our understanding of the translation-initiation process has
      expanded greatly in recent years. In this review, we discuss various aspects of
      translation initiation, as well as signaling pathways that might be involved in
      coupling neurotransmitter and neurotrophin receptors to the translation machinery
      during various forms of synaptic plasticity.

PMID- 15254215
TI  - Activation of midbrain structures by associative novelty and the formation of
      explicit memory in humans.
AB  - Recent evidence suggests a close functional relationship between memory formation
      in the hippocampus and dopaminergic neuromodulation originating in the ventral
      tegmental area and medial substantia nigra of the midbrain. Here we report
      midbrain activation in two functional MRI studies of visual memory in healthy
      young adults. In the first study, participants distinguished between familiar and
      novel configurations of pairs of items which had been studied together by either
      learning the location or the identity of the items. In the second study,
      participants studied words by either rating the words' pleasantness or counting
      syllables. The ventral tegmental area and medial substantia nigra showed
      increased activation by associative novelty (first study) and subsequent free
      recall performance (second study). In both studies, this activation accompanied
      hippocampal activation, but was unaffected by the study task. Thus midbrain
      regions seem to participate selectively in hippocampus-dependent processes of
      associative novelty and explicit memory formation, but appear to be unaffected by
      other task-relevant aspects.

PMID- 15254216
TI  - AX+, BX- discrimination learning in the fear-potentiated startle paradigm:
      possible relevance to inhibitory fear learning in extinction.
AB  - The neural mechanisms of fear suppression most commonly are studied through the
      use of extinction, a behavioral procedure in which a feared stimulus (i.e., one
      previously paired with shock) is nonreinforced repeatedly, leading to a reduction
      or elimination of the fear response. Although extinction is perhaps the most
      convenient index of fear inhibition, a great deal of behavioral work suggests
      that postextinction training conditioned stimuli are both excitatory and
      inhibitory, making it difficult to determine whether a neural manipulation
      affects inhibition, excitation, or some combination thereof. For this reason we
      sought to develop a behavioral procedure that would render a stimulus primarily
      inhibitory while at the same time avoiding some of the issues raised by the
      traditional conditioned inhibition paradigm, namely second-order conditioning,
      external inhibition, and configural learning. Using the fear-potentiated startle
      paradigm, we adapted an AX+, BX- training procedure in which stimuli A and X were
      presented simultaneously and paired with shock, and stimuli B and X were
      presented simultaneously in the absence of shock. In testing, high levels of fear
      potentiated startle were seen in the presence of A and AX and much lower levels
      were seen in the presence of B and AB, as would be predicted if stimulus B were a
      conditioned inhibitor. We believe this method is a viable alternative to the
      traditional conditioned inhibition training procedure and will be useful for
      studying the neural mechanisms of fear inhibition.

PMID- 15254217
TI  - Noradrenergic action in prefrontal cortex in the late stage of memory
      consolidation.
AB  - These experiments investigated the role of the noradrenergic system in the late
      stage of memory consolidation and in particular its action at beta receptors in
      the prelimbic region (PL) of the prefrontal cortex in the hours after training.
      Rats were trained in a rapidly acquired, appetitively motivated foraging task
      based on olfactory discrimination. They were injected with a beta adrenergic
      receptor antagonist into the PL 5 min or 2 h after training and tested 48 h
      later. Rats injected at 2 h showed amnesia, whereas those injected at 5 min had
      good retention, equivalent to saline-injected controls. Monitoring extracellular
      noradrenaline efflux in PL by in vivo microdialysis during the first hours after
      training revealed a significant increase shortly after training, with a rapid
      return to baseline, and then another increase around the 2-h posttraining time
      window. Pseudo-trained rats showed a smaller early efflux and did not show the
      second wave of efflux at 2 h. These results confirm earlier pharmacological and
      immunohistochemical studies suggesting a delayed role of noradrenaline in a late
      phase of long-term memory consolidation and the engagement of the PL during these
      consolidation processes.

PMID- 15254218
TI  - Extending in vitro conditioning in Aplysia to analyze operant and classical
      processes in the same preparation.
AB  - Operant and classical conditioning are major processes shaping behavioral
      responses in all animals. Although the understanding of the mechanisms of
      classical conditioning has expanded significantly, the understanding of the
      mechanisms of operant conditioning is more limited. Recent developments in
      Aplysia are helping to narrow the gap in the level of understanding between
      operant and classical conditioning, and have raised the possibility of studying
      the neuronal processes underlying the interaction of operant and classical
      components in a relatively complex learning task. In the present study, we
      describe a first step toward realizing this goal, by developing a single in vitro
      preparation in which both operant and classical conditioning can be studied
      concurrently. The new paradigm reproduced previously published results, even
      under more conservative and homogenous selection criteria and tonic stimulation
      regime. Moreover, the observed learning was resistant to delay, shortening, and
      signaling of reinforcement.

PMID- 15254219
TI  - The hippocampus and memory for "what," "where," and "when".
AB  - Previous studies have indicated that nonhuman animals might have a capacity for
      episodic-like recall reflected in memory for "what" events that happened "where"
      and "when". These studies did not identify the brain structures that are critical
      to this capacity. Here we trained rats to remember single training episodes, each
      composed of a series of odors presented in different places on an open field.
      Additional assessments examined the individual contributions of odor and spatial
      cues to judgments about the order of events. The results indicated that normal
      rats used a combination of spatial ("where") and olfactory ("what") cues to
      distinguish "when" events occurred. Rats with lesions of the hippocampus failed
      in using combinations of spatial and olfactory cues, even as evidence from probe
      tests and initial sampling behavior indicated spared capacities for perception of
      spatial and odor cues, as well as some form of memory for those individual cues.
      These findings indicate that rats integrate "what," "where," and "when"
      information in memory for single experiences, and that the hippocampus is
      critical to this capacity.

PMID- 15254221
TI  - Role of Aplysia cell adhesion molecules during 5-HT-induced long-term functional
      and structural changes.
AB  - We previously reported that five repeated pulses of 5-HT lead to down-regulation
      of the TM-apCAM isoform at the surface of Aplysia sensory neurons (SNs). We here
      examined whether apCAM down-regulation is required for 5-HT-induced long-term
      facilitation. We also analyzed the role of the cytoplasmic and extracellular
      domains by overexpressing various apCAM mutants by DNA microinjection. When TM
      apCAM was up-regulated in SNs by DNA microinjection, five pulses of 5-HT failed
      to produce either synaptic facilitation or an enhancement of synaptic growth,
      suggesting that down-regulation of apCAM is required for 5-HT-induced EPSP
      enhancement and new varicosity formation. However, disrupting the extracellular
      domain function of overexpressed apCAM with a specific antibody restored 5-HT
      induced excitatory postsynaptic potential increase but not synaptic growth. The
      overexpression of the MAP Kinase mutant of TM-apCAM, which is not internalized by
      5-HT, inhibited new varicosity formation, but did not inhibit excitatory
      postsynaptic potential increase. Deletion mutants containing only the cytoplasmic
      portion of apCAM blocked 5-HT-induced synaptic growth but not excitatory
      postsynaptic potential increase. Thus, our data suggest that TM-apCAM may act as
      a suppressor of both synaptic-strength enhancement in pre-existing synapses and
      of new synaptic varicosity formation in the nonsynaptic region, via different
      mechanisms.

PMID- 15254220
TI  - Intra-amygdala muscimol injections impair freezing and place avoidance in
      aversive contextual conditioning.
AB  - Rats were trained by shocking them in a closed compartment. When subsequently
      tested in the same closed compartment with no shock, normal rats showed an
      increased tendency to freeze. They also showed an increased tendency to actively
      avoid the compartment when given access to an adjacent neutral compartment for
      the first time. Amygdala inactivation with bilateral muscimol injections before
      training attenuated freezing and eliminated avoidance during the test. Rats
      trained in a normal state and given intra-amygdala muscimol injections before the
      test did not freeze or avoid the shock-paired compartment. This pattern of
      effects suggests that amygdala inactivation during training impaired acquisition
      of a conditioned response (CR) due either to inactivation of a neural substrate
      essential for its storage or to elimination of a memory modulation effect that
      facilitates its storage in some other brain region(s). The elimination of both
      freezing and active avoidance by amygdala inactivation during testing suggests
      that neither of these behaviors is the CR. The possibility that the CR is a set
      of internal responses that produces both freezing and avoidance as well as other
      behavioral effects is discussed.

PMID- 15254222
TI  - Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of
      eukaryotic initiation factor 4E but not for cell growth or development.
AB  - Mnk1 and Mnk2 are protein kinases that are directly phosphorylated and activated
      by extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein
      (MAP) kinases and implicated in the regulation of protein synthesis through their
      phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) at Ser209.
      To investigate their physiological functions, we generated mice lacking the Mnk1
      or Mnk2 gene or both; the resulting KO mice were viable, fertile, and developed
      normally. In embryonic fibroblasts prepared from Mnk1-Mnk2 DKO mice, eIF4E was
      not detectably phosphorylated at Ser209, even when the ERK and/or p38 MAP kinases
      were activated. Analysis of embryonic fibroblasts from single KO mice revealed
      that Mnk1 is responsible for the inducible phosphorylation of eIF4E in response
      to MAP kinase activation, whereas Mnk2 mainly contributes to eIF4E's basal,
      constitutive phosphorylation. Lipopolysaccharide (LPS)- or insulin-induced
      upregulation of eIF4E phosphorylation in the spleen, liver, or skeletal muscle
      was abolished in Mnk1(-/-) mice, whereas the basal eIF4E phosphorylation levels
      were decreased in Mnk2(-/-) mice. In Mnk1-Mnk2 DKO mice, no phosphorylated eIF4E
      was detected in any tissue studied, even after LPS or insulin injection. However,
      neither general protein synthesis nor cap-dependent translation, as assayed by a
      bicistronic reporter assay system, was affected in Mnk-deficient embryonic
      fibroblasts, despite the absence of phosphorylated eIF4E. Thus, Mnk1 and Mnk2 are
      exclusive eIF4E kinases both in cultured fibroblasts and adult tissues, and they
      regulate inducible and constitutive eIF4E phosphorylation, respectively. These
      results strongly suggest that eIF4E phosphorylation at Ser209 is not essential
      for cell growth during development.

PMID- 15254224
TI  - Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad
      mediated down-regulation of Cdk6.
AB  - Because a temporal arrest in the G(1) phase of the cell cycle is thought to be a
      prerequisite for cell differentiation, we investigated cell cycle factors that
      critically influence the differentiation of mouse osteoblastic MC3T3-E1 cells
      induced by bone morphogenetic protein 2 (BMP-2), a potent inducer of osteoblast
      differentiation. Of the G(1) cell cycle factors examined, the expression of
      cyclin-dependent kinase 6 (Cdk6) was found to be strongly down-regulated by BMP
      2/Smads signaling, mainly via transcriptional repression. The enforced expression
      of Cdk6 blocked BMP-2-induced osteoblast differentiation to various degrees,
      depending on the level of its overexpression. However, neither BMP-2 treatment
      nor Cdk6 overexpression significantly affected cell proliferation, suggesting
      that the inhibitory effect of Cdk6 on cell differentiation was exerted by a
      mechanism that is largely independent of its cell cycle regulation. These results
      indicate that Cdk6 is a critical regulator of BMP-2-induced osteoblast
      differentiation and that its Smads-mediated down-regulation is essential for
      efficient osteoblast differentiation.

PMID- 15254223
TI  - The microphthalmia transcription factor (Mitf) controls expression of the ocular
      albinism type 1 gene: link between melanin synthesis and melanosome biogenesis.
AB  - Melanogenesis is the process that regulates skin and eye pigmentation. Albinism,
      a genetic disease causing pigmentation defects and visual disorders, is caused by
      mutations in genes controlling either melanin synthesis or melanosome biogenesis.
      Here we show that a common transcriptional control regulates both of these
      processes. We performed an analysis of the regulatory region of Oa1, the murine
      homolog of the gene that is mutated in the X-linked form of ocular albinism, as
      Oa1's function affects melanosome biogenesis. We demonstrated that Oa1 is a
      target of Mitf and that this regulatory mechanism is conserved in the human gene.
      Tissue-specific control of Oa1 transcription lies within a region of 617 bp that
      contains the E-box bound by Mitf. Finally, we took advantage of a virus-based
      system to assess tissue specificity in vivo. To this end, a small fragment of the
      Oa1 promoter was cloned in front of a reporter gene in an adeno-associated virus.
      After we injected this virus into the subretinal space, we observed reporter gene
      expression specifically in the retinal pigment epithelium, confirming the cell
      specific expression of the Oa1 promoter in the eye. The results obtained with
      this viral system are a preamble to the development of new gene delivery
      approaches for the treatment of retinal pigment epithelium defects.

PMID- 15254225
TI  - Menin missense mutants associated with multiple endocrine neoplasia type 1 are
      rapidly degraded via the ubiquitin-proteasome pathway.
AB  - MEN1 is a tumor suppressor gene that is responsible for multiple endocrine
      neoplasia type 1 (MEN1) and that encodes a 610-amino-acid protein, called menin.
      While the majority of germ line mutations identified in MEN1 patients are
      frameshift and nonsense mutations resulting in truncation of the menin protein,
      various missense mutations have been identified whose effects on menin activity
      are unclear. For this study, we analyzed a series of menin proteins with single
      amino acid alterations and found that all of the MEN1-causing missense mutations
      tested led to greatly diminished levels of the affected proteins in comparison
      with wild-type and benign polymorphic menin protein levels. We demonstrate here
      that the reduced levels of the mutant proteins are due to rapid degradation via
      the ubiquitin-proteasome pathway. Furthermore, the mutants, but not wild-type
      menin, interact both with the molecular chaperone Hsp70 and with the Hsp70
      associated ubiquitin ligase CHIP, and the overexpression of CHIP promotes the
      ubiquitination of the menin mutants in vivo. These findings reveal that MEN1
      causing missense mutations lead to a loss of function of menin due to enhanced
      proteolytic degradation, which may be a common mechanism for inactivating tumor
      suppressor gene products in familial cancer.

PMID- 15254226
TI  - Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible
      nuclear receptor coregulator.
AB  - The transcriptional activity of estrogen receptor alpha (ER-alpha) is modified by
      regulatory action and interactions of coactivators and corepressors. Recent
      studies have shown that the metastasis-associated protein 1 (MTA1) represses
      estrogen receptor element (ERE)-driven transcription in breast cancer cells. With
      a yeast two-hybrid screen to clone MTA1-interacting proteins, we identified a
      known nuclear receptor coregulator (NRIF3) as an MTA1-binding protein. NRIF3
      interacted with MTA1 both in vitro and in vivo. NRIF3 bound to the C-terminal
      region of MTA1, while MTA1 bound to the N-terminal region of NRIF3, containing
      one nuclear receptor interaction LXXLL motif. We showed that NRIF3 is an ER
      coactivator, hyperstimulated ER transactivation functions, and associated with
      the endogenous ER and its target gene promoter. MTA1 repressed NRIF3-mediated
      stimulation of ERE-driven transcription and interfered with NRIF3's association
      with the ER target gene chromatin. In addition, NRIF3 deregulation enhanced the
      responsiveness of breast cancer cells to estrogen-induced stimulation of growth
      and anchorage independence. Furthermore, we found that NRIF3 is an estrogen
      inducible gene and activated ER associated with the ER response element in the
      NRIF3 gene promoter. These findings suggest that NRIF3, an MTA1-interacting
      protein, is an estrogen-inducible gene and that regulatory interactions between
      MTA1 and NRIF3 might be important in modulating the sensitivity of breast cancer
      cells to estrogen.

PMID- 15254227
TI  - Association of active caspase 8 with the mitochondrial membrane during apoptosis:
      potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion
      endoplasmic reticulum cross talk in etoposide-induced cell death.
AB  - It was recently demonstrated that during apoptosis, active caspase 9 and caspase
      3 rapidly accumulate in the mitochondrion-enriched membrane fraction (D. Chandra
      and D. G. Tang, J. Biol. Chem.278:17408-17420, 2003). We now show that active
      caspase 8 also becomes associated with the membranes in apoptosis caused by
      multiple stimuli. In MDA-MB231 breast cancer cells treated with etoposide (VP16),
      active caspase 8 is detected only in the membrane fraction, which contains both
      mitochondria and endoplasmic reticulum (ER), as revealed by fractionation
      studies. Immunofluorescence microscopy, however, shows that procaspase 8 and
      active caspase 8 predominantly colocalize with the mitochondria. Biochemical
      analysis demonstrates that both procaspase 8 and active caspase 8 are localized
      mainly on the outer mitochondrial membrane (OMM) as integral proteins. Functional
      analyses with dominant-negative mutants, small interfering RNAs, peptide
      inhibitors, and Fas-associated death domain (FADD)- and caspase 8-deficient
      Jurkat T cells establish that the mitochondrion-localized active caspase 8
      results mainly from the FADD-dependent and tumor necrosis factor receptor
      associated death domain-dependent mechanisms and that caspase 8 activation plays
      a causal role in VP16-induced caspase 3 activation and cell death. Finally, we
      present evidence that the OMM-localized active caspase 8 can activate cytosolic
      caspase 3 and ER-localized BAP31. Cleavage of BAP31 leads to the generation of ER
      localized, proapoptotic BAP20, which may mediate mitochondrion-ER cross talk
      through a Ca(2+)-dependent mechanism.

PMID- 15254228
TI  - Nucleocytoplasmic shuttling of JAZ, a new cargo protein for exportin-5.
AB  - Exportin-5 is a nuclear export receptor for certain classes of double-stranded
      RNA (dsRNA), including pre-micro-RNAs, viral hairpin RNAs, and some tRNAs. It can
      also export the RNA binding proteins ILF3 and elongation factor EF1A. However,
      the rules that determine which RNA binding proteins are exportin-5 cargoes remain
      unclear. JAZ possesses an unusual dsRNA binding domain consisting of multiple
      C2H2 zinc fingers. We found that JAZ binds to exportin-5 in a Ran-GTP- and dsRNA
      dependent manner. Exportin-5 stimulates JAZ shuttling, and gene silencing of
      exportin-5 reduces shuttling. Recombinant exportin-5 also stimulates nuclear
      export of JAZ in permeabilized cells. JAZ also binds to ILF3, and surprisingly,
      this interaction is RNA independent, even though it requires the dsRNA binding
      domains of ILF3. Exportin-5, JAZ, and ILF3 can form a heteromeric complex with
      Ran-GTP and dsRNA, and JAZ increases ILF3 binding to exportin-5. JAZ does not
      contain a classical nuclear localization signal, and in digitonin-permeabilized
      cells, nuclear accumulation of JAZ does not require energy or cytosol.
      Nonetheless, low temperatures prevent JAZ import, suggesting that nuclear entry
      does not occur via simple diffusion. Together, these data suggest that JAZ is
      exported by exportin-5 but translocates back into nuclei by a facilitated
      diffusion mechanism.

PMID- 15254229
TI  - Functional complementation of human centromere protein A (CENP-A) by Cse4p from
      Saccharomyces cerevisiae.
AB  - We have employed a novel in vivo approach to study the structure and function of
      the eukaryotic kinetochore multiprotein complex. RNA interference (RNAi) was used
      to block the synthesis of centromere protein A (CENP-A) and Clip-170 in human
      cells. By coexpression, homologous kinetochore proteins from Saccharomyces
      cerevisiae were then tested for the ability to complement the RNAi-induced
      phenotypes. Cse4p, the budding yeast CENP-A homolog, was specifically
      incorporated into kinetochore nucleosomes and was able to complement RNAi-induced
      cell cycle arrest in CENP-A-depleted human cells. Thus, Cse4p can structurally
      and functionally substitute for CENP-A, strongly suggesting that the basic
      features of centromeric chromatin are conserved between yeast and mammals. Bik1p,
      the budding yeast homolog of human CLIP-170, also specifically localized to
      kinetochores during mitosis, but Bik1p did not rescue CLIP-170 depletion-induced
      cell cycle arrest. Generally, the newly developed in vivo complementation assay
      provides a powerful new tool for studying the function and evolutionary
      conservation of multiprotein complexes from yeast to humans.

PMID- 15254230
TI  - Telomere-associated protein TIN2 is essential for early embryonic development
      through a telomerase-independent pathway.
AB  - TIN2 is a negative regulator of telomere elongation that interacts with telomeric
      DNA repeat binding factor 1 (TRF1) and affects telomere length by a telomerase
      dependent mechanism. Here we show that inactivation of the mouse TRF1-interacting
      protein 2 (TIN2) gene results in early embryonic lethality. We further observed
      that the embryonic lethality of TIN2 mutant mice was not affected by inactivation
      of the telomerase reverse transcriptase gene, indicating that embryonic lethality
      is not the result of telomerase-dependent changes in telomere length or function.
      Our findings suggest that TIN2 has a role independent of telomere length
      regulation that is essential for embryonic development and cell viability.

PMID- 15254231
TI  - Gene targeting reveals a widespread role for the high-mobility-group
      transcription factor Sox11 in tissue remodeling.
AB  - The high-mobility-group domain-containing transcription factor Sox11 is expressed
      transiently during embryonic development in many tissues that undergo inductive
      remodeling. Here we have analyzed the function of Sox11 by gene deletion in the
      mouse. Sox11-deficient mice died at birth from congenital cyanosis, likely
      resulting from heart defects. These included ventricular septation defects and
      outflow tract malformations that ranged from arterial common trunk to a condition
      known as double outlet right ventricle. Many other organs that normally express
      Sox11 also exhibited severe developmental defects. We observed various
      craniofacial and skeletal malformations, asplenia, and hypoplasia of the lung,
      stomach, and pancreas. Eyelids and the abdominal wall did not close properly in
      some Sox11-deficient mice. This phenotype suggests a prime function for Sox11 in
      tissue remodeling and identifies SOX11 as a potentially mutated gene in
      corresponding human malformation syndromes.

PMID- 15254232
TI  - Vitamin C is a kinase inhibitor: dehydroascorbic acid inhibits IkappaBalpha
      kinase beta.
AB  - Reactive oxygen species (ROS) are key intermediates in cellular signal
      transduction pathways whose function may be counterbalanced by antioxidants.
      Acting as an antioxidant, ascorbic acid (AA) donates two electrons and becomes
      oxidized to dehydroascorbic acid (DHA). We discovered that DHA directly inhibits
      IkappaBalpha kinase beta (IKKbeta) and IKKalpha enzymatic activity in vitro,
      whereas AA did not have this effect. When cells were loaded with AA and induced
      to generate DHA by oxidative stress in cells expressing a constitutive active
      IKKbeta, NF-kappaB activation was inhibited. Our results identify a dual
      molecular action of vitamin C in signal transduction and provide a direct linkage
      between the redox state of vitamin C and NF-kappaB signaling events. AA quenches
      ROS intermediates involved in the activation of NF-kappaB and is oxidized to DHA,
      which directly inhibits IKKbeta and IKKalpha enzymatic activity. These findings
      define a function for vitamin C in signal transduction other than as an
      antioxidant and mechanistically illuminate how vitamin C down-modulates NF-kappaB
      signaling.

PMID- 15254233
TI  - Genetic evidence for functional dependency of p18Ink4c on Cdk4.
AB  - The INK4 family of cyclin-dependent kinase (CDK) inhibitors negatively regulates
      cyclin D-dependent CDK4 and CDK6 and induces the growth-suppressive function of
      Rb family proteins. Mutations in the Cdk4 gene conferring INK4 resistance are
      associated with familial and sporadic melanoma in humans and result in a wide
      spectrum of tumors in mice, suggesting that INK4 is a major regulator of CDK4.
      Mice lacking the Cdk4 gene exhibit various defects in many organs associated with
      hypocellularity, whereas loss of the p18(Ink4c) gene results in widespread
      hyperplasia and organomegaly. To genetically test the notion that the function of
      INK4 is dependent on CDK4, we generated p18; Cdk4 double-mutant mice and examined
      the organs and tissues which developed abnormalities when either gene is deleted.
      We show here that, in all organs we have examined, including pituitary, testis,
      pancreas, kidney, and adrenal gland, hyperproliferative phenotypes associated
      with p18 loss were canceled. The double-mutant mice exhibited phenotypes very
      close to or indistinguishable from that of Cdk4 single-mutant mice. Mice lacking
      p27(Kip1) develop widespread hyperplasia and organomegaly similar to those
      developed by p18-deficient mice. The p27; Cdk4 double-mutant mice, however,
      displayed phenotypes intermediate between those of p27 and Cdk4 single-mutant
      mice. These results provide genetic evidence that in mice p18(Ink4c) and
      p27(Kip1) mediate the transduction of different cell growth and proliferation
      signals to CDK4 and that p18(Ink4c) is functionally dependent on CDK4.

PMID- 15254234
TI  - Nucleotide exchange factor ECT2 interacts with the polarity protein complex
      Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity.
AB  - Regulation of cell polarity is an important biological event that governs diverse
      cell functions such as localization of embryonic determinants and establishment
      of tissue and organ architecture. The Rho family GTPases and the polarity complex
      Par6/Par3/atypical protein kinase C (PKC) play a key role in the signaling
      pathway, but the molecules that regulate upstream signaling are still not known.
      Here we identified the guanine nucleotide exchange factor ECT2 as an activator of
      the polarity complex. ECT2 interacted with Par6 as well as Par3 and PKCzeta.
      Coexpression of Par6 and ECT2 efficiently activated Cdc42 in vivo. Overexpression
      of ECT2 also stimulated the PKCzeta activity, whereas dominant-negative ECT2
      inhibited the increase in PKCzeta activity stimulated by Par6. ECT2 localization
      was detected at sites of cell-cell contact as well as in the nucleus of MDCK
      cells. The expression and localization of ECT2 were regulated by calcium, which
      is a critical regulator of cell-cell adhesion. Together, these results suggest
      that ECT2 regulates the polarity complex Par6/Par3/PKCzeta and possibly plays a
      role in epithelial cell polarity.

PMID- 15254235
TI  - Drosophila C-terminal Src kinase negatively regulates organ growth and cell
      proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT
      pathways.
AB  - Src family kinases regulate multiple cellular processes including proliferation
      and oncogenesis. C-terminal Src kinase (Csk) encodes a critical negative
      regulator of Src family kinases. We demonstrate that the Drosophila melanogaster
      Csk ortholog, dCsk, functions as a tumor suppressor: dCsk mutants display organ
      overgrowth and excess cellular proliferation. Genetic analysis indicates that the
      dCsk(-/-) overgrowth phenotype results from activation of Src, Jun kinase, and
      STAT signal transduction pathways. In particular, blockade of STAT function in
      dCsk mutants severely reduced Src-dependent overgrowth and activated apoptosis of
      mutant tissue. Our data provide in vivo evidence that Src activity requires JNK
      and STAT function.

PMID- 15254236
TI  - Rap1 regulates the formation of E-cadherin-based cell-cell contacts.
AB  - In epithelial tissues, cells are linked to their neighbors through specialized
      cell-cell adhesion proteins. E-cadherin is one of the most important membrane
      proteins for the establishment of intimate cell-cell contacts, but the molecular
      mechanism by which it is recruited to contact sites is largely unknown. We report
      here that the cytoplasmic domain of E-cadherin interacts with C3G, a guanine
      nucleotide exchange factor for Rap1. In epithelial cell cultures, ligation of the
      extracellular domain of E-cadherin enhances Rap1 activity, which in turn is
      necessary for the proper targeting of E-cadherin molecules to maturing cell-cell
      contacts. Furthermore, our data suggest that Cdc42 functions downstream of Rap1
      in this process. We conclude that Rap1 plays a vital role in the establishment of
      E-cadherin-based cell-cell adhesion.

PMID- 15254237
TI  - BRCA1 is required for common-fragile-site stability via its G2/M checkpoint
      function.
AB  - Common fragile sites are loci that form chromosome gaps or breaks when DNA
      synthesis is partially inhibited. Fragile sites are prone to deletions,
      translocations, and other rearrangements that can cause the inactivation of
      associated tumor suppressor genes in cancer cells. It was previously shown that
      ATR is critical to fragile-site stability and that ATR-deficient cells have
      greatly elevated fragile-site expression (A. M. Casper, P. Nghiem, M. F. Arlt,
      and T. W. Glover, Cell 111:779-789, 2002). Here we demonstrate that mouse and
      human cells deficient for BRCA1, due to mutation or knockdown by RNA
      interference, also have elevated fragile-site expression. We further show that
      BRCA1 functions in the induction of the G(2)/M checkpoint after aphidicolin
      induced replication stalling and that this checkpoint function is involved in
      fragile-site stability. These data indicate that BRCA1 is important in fragile
      site stability and that fragile sites are recognized by the G(2)/M checkpoint
      pathway, in which BRCA1 plays a key role. Furthermore, they suggest that
      mutations in BRCA1 or interacting proteins could lead to rearrangements at
      fragile sites in cancer cells.

PMID- 15254238
TI  - mTOR is essential for growth and proliferation in early mouse embryos and
      embryonic stem cells.
AB  - TOR is a serine-threonine kinase that was originally identified as a target of
      rapamycin in Saccharomyces cerevisiae and then found to be highly conserved among
      eukaryotes. In Drosophila melanogaster, inactivation of TOR or its substrate, S6
      kinase, results in reduced cell size and embryonic lethality, indicating a
      critical role for the TOR pathway in cell growth control. However, the in vivo
      functions of mammalian TOR (mTOR) remain unclear. In this study, we disrupted the
      kinase domain of mouse mTOR by homologous recombination. While heterozygous
      mutant mice were normal and fertile, homozygous mutant embryos died shortly after
      implantation due to impaired cell proliferation in both embryonic and
      extraembryonic compartments. Homozygous blastocysts looked normal, but their
      inner cell mass and trophoblast failed to proliferate in vitro. Deletion of the C
      terminal six amino acids of mTOR, which are essential for kinase activity,
      resulted in reduced cell size and proliferation arrest in embryonic stem cells.
      These data show that mTOR controls both cell size and proliferation in early
      mouse embryos and embryonic stem cells.

PMID- 15254239
TI  - Gene-targeted mice lacking the Trex1 (DNase III) 3'-->5' DNA exonuclease develop
      inflammatory myocarditis.
AB  - TREX1, originally designated DNase III, was isolated as a major nuclear DNA
      specific 3'-->5' exonuclease that is widely distributed in both proliferating and
      nonproliferating mammalian tissues. The cognate cDNA shows homology to the
      editing subunit of the Escherichia coli replicative DNA polymerase III holoenzyme
      and encodes an exonuclease which was able to serve a DNA-editing function in
      vitro, promoting rejoining of a 3' mismatched residue in a reconstituted DNA base
      excision repair system. Here we report the generation of gene-targeted Trex1(-/-)
      mice. The null mice are viable and do not show the increase in spontaneous
      mutation frequency or cancer incidence that would be predicted if Trex1 served an
      obligatory role of editing mismatched 3' termini generated during DNA repair or
      DNA replication in vivo. Unexpectedly, Trex1(-/-) mice exhibit a dramatically
      reduced survival and develop inflammatory myocarditis leading to progressive,
      often dilated, cardiomyopathy and circulatory failure.

PMID- 15254240
TI  - In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death
      in response to DNA damage that can precede p53 target gene activation.
AB  - p53 promotes apoptosis in response to death stimuli by transactivation of target
      genes and by transcription-independent mechanisms. We recently showed that wild
      type p53 rapidly translocates to mitochondria in response to multiple death
      stimuli in cultured cells. Mitochondrial p53 physically interacts with
      antiapoptotic Bcl proteins, induces Bak oligomerization, permeabilizes
      mitochondrial membranes, and rapidly induces cytochrome c release. Here we
      characterize the mitochondrial p53 response in vivo. Mice were subjected to gamma
      irradiation or intravenous etoposide administration, followed by cell
      fractionation and immunofluorescence studies of various organs. Mitochondrial p53
      accumulation occurred in radiosensitive organs like thymus, spleen, testis, and
      brain but not in liver and kidney. Of note, mitochondrial p53 translocation was
      rapid (detectable at 30 min in thymus and spleen) and triggered an early wave of
      marked caspase 3 activation and apoptosis. This caspase 3-mediated apoptosis was
      entirely p53 dependent, as shown by p53 null mice, and preceded p53 target gene
      activation. The transcriptional p53 program had a longer lag phase than the rapid
      mitochondrial p53 program. In thymus, the earliest apoptotic target gene products
      PUMA, Noxa, and Bax appeared at 2, 4, and 8 h, respectively, while Bid,
      Killer/DR5, and p53DinP1 remained uninduced even after 20 h. Target gene
      induction then led to further increase in active caspase 3. Similar biphasic
      kinetics was seen in cultured human cells. Our results suggest that in sensitive
      organs mitochondrial p53 accumulation in vivo occurs soon after a death stimulus,
      triggering a rapid first wave of apoptosis that is transcription independent and
      may precede a second slower wave that is transcription dependent.

PMID- 15254241
TI  - Dissection of a natural RNA silencing process in the Drosophila melanogaster germ
      line.
AB  - To date, few natural cases of RNA-silencing-mediated regulation have been
      described. Here, we analyzed repression of testis-expressed Stellate genes by the
      homologous Suppressors of Stellate [Su(Ste)] repeats that produce sense and
      antisense short RNAs. The Stellate promoter is dispensable for suppression, but
      local disturbance of complementarity between the Stellate transcript and the
      Su(Ste) repeats impairs silencing. Using in situ RNA hybridization, we found
      temporal control of the expression and spatial distribution of sense and
      antisense Stellate and Su(Ste) transcripts in germinal cells. Antisense Su(Ste)
      transcripts accumulate in the nuclei of early spermatocytes before the appearance
      of sense transcripts. The sense and antisense transcripts are colocalized in the
      nuclei of mature spermatocytes, placing the initial step of silencing in the
      nucleus and suggesting formation of double-stranded RNA. Mutations in the
      aubergine and spindle-E genes, members of the Argonaute and RNA helicase gene
      families, respectively, impair silencing by eliminating the short Su(Ste) RNA,
      but have no effect on microRNA production. Thus, different small RNA-containing
      complexes operate in the male germ line.

PMID- 15254242
TI  - Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells:
      potential mechanism by which the hormone favorably affects hematopoietic stem
      cells.
AB  - Members of the homeobox family of transcription factors are major regulators of
      hematopoiesis. Overexpression of either HOXB4 or HOXA9 in primitive marrow cells
      enhances the expansion of hematopoietic stem cells (HSCs). However, little is
      known of how expression or function of these proteins is regulated during
      hematopoiesis under physiological conditions. In our previous studies we
      demonstrated that thrombopoietin (TPO) enhances levels of HOXB4 mRNA in primitive
      hematopoietic cells (K. Kirito, N. Fox, and K. Kaushansky, Blood 102:3172-3178,
      2003). To extend our studies, we investigated the effects of TPO on HOXA9 in this
      same cell population. Although overall levels of the transcription factor were
      not affected, we found that TPO induced the nuclear import of HOXA9 both in UT
      7/TPO cells and in primitive Sca-1(+)/c-kit(+)/Gr-1(-) hematopoietic cells in a
      mitogen-activated protein kinase-dependent fashion. TPO also controlled MEIS1
      expression at mRNA levels, at least in part due to phosphatidylinositol 3-kinase
      activation. Collectively, TPO modulates the function of HOXA9 by leading to its
      nuclear translocation, likely mediated by effects on its partner protein MEIS1,
      and potentially due to two newly identified nuclear localization signals. Our
      data suggest that TPO controls HSC development through the regulation of multiple
      members of the Hox family of transcription factors through multiple mechanisms.

PMID- 15254243
TI  - Reactive nitrogen species-induced cell death requires Fas-dependent activation of
      c-Jun N-terminal kinase.
AB  - Nitrogen dioxide is a highly toxic reactive nitrogen species (RNS) recently
      discovered as an inflammatory oxidant with great potential to damage tissues. We
      demonstrate here that cell death by RNS was caused by c-Jun N-terminal kinase
      (JNK). Activation of JNK by RNS was density dependent and caused mitochondrial
      depolarization and nuclear condensation. JNK activation by RNS was abolished in
      cells lacking functional Fas or following expression of a truncated version of
      Fas lacking the intracellular death domain. In contrast, RNS induced JNK potently
      in cells expressing a truncated version of tumor necrosis factor receptor 1 or
      cells lacking tumor necrosis factor receptor 1 (TNF-R1), illustrating a
      dependence of Fas but not TNF-R1 in RNS-induced signaling to JNK. Furthermore,
      Fas was oxidized, redistributed, and colocalized with Fas-associated death domain
      (FADD) in RNS-exposed cells, illustrating that RNS directly targeted Fas. JNK
      activation and cell death by RNS occurred in a Fas ligand- and caspase
      independent manner. While the activation of JNK by RNS or FasL required FADD, the
      cysteine-rich domain 1 containing preligand assembly domain required for FasL
      signaling was not involved in JNK activation by RNS. These findings illustrate
      that RNS cause cell death in a Fas- and JNK-dependent manner and that this occurs
      through a pathway distinct from FasL. Thus, avenues aimed at preventing the
      interaction of RNS with Fas may attenuate tissue damage characteristic of chronic
      inflammatory diseases that are accompanied by high levels of RNS.

PMID- 15254244
TI  - Global mRNA stabilization preferentially linked to translational repression
      during the endoplasmic reticulum stress response.
AB  - The stability of mRNAs undergoing translation has long been a controversial
      question. Here, we systematically investigate links between mRNA turnover and
      translation during the endoplasmic reticulum (ER) stress response, a process
      during which protein synthesis is potently regulated. cDNA array-based approaches
      to assess the stability and translational status of each mRNA were devised.
      First, ER stress-triggered changes in mRNA stability were studied by comparing
      differences in steady-state mRNA levels with differences in gene transcription.
      Second, changes in translational status were monitored by studying ER stress
      induced shifts in the relative distribution of each mRNA along sucrose gradients.
      Together, the array-derived data reveal complex links between mRNA stability and
      translation, with all regulatory groups represented: both stabilized and
      destabilized mRNAs were found among translationally induced as well as
      translationally suppressed mRNA collections. Remarkably, however, the subset of
      stabilized mRNAs was prominently enriched in translationally suppressed
      transcripts, suggesting that ER stress was capable of causing the stabilization
      of mRNAs associated with a global reduction in protein synthesis. The cDNA array
      based approach described here can be applied to global analyses of mRNA turnover
      and translation and can serve to investigate subsets of mRNAs subject to joint
      posttranscriptional control.

PMID- 15254245
TI  - RACK1 regulates G1/S progression by suppressing Src kinase activity.
AB  - Cancer genes exert their greatest influence on the cell cycle by targeting
      regulators of a critical checkpoint in late G(1). Once cells pass this
      checkpoint, they are fated to replicate DNA and divide. Cancer cells subvert
      controls at work at this restriction point and remain in cycle. Previously, we
      showed that RACK1 inhibits the oncogenic Src tyrosine kinase and NIH 3T3 cell
      growth. RACK1 inhibits cell growth, in part, by prolonging G(0)/G(1). Here we
      show that RACK1 overexpression induces a partial G(1) arrest by suppressing Src
      activity at the G(1) checkpoint. RACK1 works through Src to inhibit Vav2, Rho
      GTPases, Stat3, and Myc. Consequently, cyclin D1 and cyclin-dependent kinases 4
      and 2 (CDK4 and CDK2, respectively) are suppressed, CDK inhibitor p27 and
      retinoblastoma protein are activated, E2F1 is sequestered, and G(1)/S progression
      is delayed. Conversely, downregulation of RACK1 by short interference RNA
      activates Src-mediated signaling, induces Myc and cyclin D1, and accelerates
      G(1)/S progression. RACK1 suppresses Src- but not mitogen-activated protein
      kinase-dependent platelet-derived growth factor signaling. We also show that
      Stat3 is required for Rac1 induction of Myc. Our results reveal a novel mechanism
      of cell cycle control in late G(1) that works via an endogenous inhibitor of the
      Src kinase.

PMID- 15254246
TI  - Three separable domains regulate GTP-dependent association of H-ras with the
      plasma membrane.
AB  - The microlocalization of Ras proteins to different microdomains of the plasma
      membrane is critical for signaling specificity. Here we examine the complex
      membrane interactions of H-ras with a combination of FRAP on live cells to
      measure membrane affinity and electron microscopy of intact plasma membrane
      sheets to spatially map microdomains. We show that three separable forces operate
      on H-ras at the plasma membrane. The lipid anchor, comprising a processed CAAX
      motif and two palmitic acid residues, generates one attractive force that
      provides a high-affinity interaction with lipid rafts. The adjacent hypervariable
      linker domain provides a second attractive force but for nonraft plasma membrane
      microdomains. Operating against the attractive interaction of the lipid anchor
      for lipid rafts is a repulsive force generated by the N-terminal catalytic domain
      that increases when H-ras is GTP loaded. These observations lead directly to a
      novel mechanism that explains how H-ras lateral segregation is regulated by
      activation state: GTP loading decreases H-ras affinity for lipid rafts and allows
      the hypervariable linker domain to target to nonraft microdomains, the primary
      site of H-ras signaling.

PMID- 15254247
TI  - SMU-2 and SMU-1, Caenorhabditis elegans homologs of mammalian spliceosome
      associated proteins RED and fSAP57, work together to affect splice site choice.
AB  - Mutations in the Caenorhabditis elegans gene smu-2 suppress mec-8 and unc-52
      mutations. It has been proposed that MEC-8 regulates the alternative splicing of
      unc-52 transcripts, which encode the core protein of perlecan, a basement
      membrane proteoglycan. We show that mutation in smu-2 leads to enhanced
      accumulation of transcripts that skip exon 17, but not exon 18, of unc-52, which
      explains our finding that smu-2 mutations suppress the uncoordination conferred
      by nonsense mutations in exon 17, but not in exon 18, of unc-52. We conclude that
      smu-2 encodes a ubiquitously expressed nuclear protein that is 40% identical to
      the human RED protein, a component of purified spliceosomes. The effects of smu-2
      mutation on both unc-52 pre-mRNA splicing and the suppression of mec-8 and unc-52
      mutant phenotypes are indistinguishable from the effects of mutation in smu-1, a
      gene that encodes a protein that is 62% identical to human spliceosome-associated
      protein fSAP57. We provide evidence that SMU-2 protects SMU-1 from degradation in
      vivo. In vitro and in vivo coimmunoprecipitation experiments indicate that SMU-2
      and SMU-1 bind to each other. We propose that SMU-2 and SMU-1 function together
      to regulate splice site choice in the pre-mRNAs of unc-52 and other genes.

PMID- 15254249
TI  - Gene expression analysis of tumor spheroids reveals a role for suppressed DNA
      mismatch repair in multicellular resistance to alkylating agents.
AB  - Drug resistance is a major obstacle in the successful treatment of cancer. Thus,
      elucidation of the mechanisms responsible is a critical first step in trying to
      prevent or delay such manifestations of resistance. In this regard, three
      dimensional multicellular tumor cell spheroids are intrinsically more resistant
      to virtually all anticancer cytotoxic drugs than conventional monolayer cultures.
      We have employed the EMT-6 subline PC5T, which forms highly compact spheroids,
      and differential display to identify candidate genes whose expression differs
      between monolayer and spheroids. Approximately 5,000 bands were analyzed,
      revealing 26 to be differentially expressed. Analysis of EMT-6 tumor variants
      selected in vivo for acquired resistance to alkylating agents identified eight
      genes whose expression correlated with drug resistance in tumor spheroids. Four
      genes (encoding Nop56, the NADH SDAP subunit, and two novel sequences) were found
      to be down-regulated in EMT-6 spheroids and four (encoding 2-oxoglutarate carrier
      protein, JTV-1, and two novel sequences) were up-regulated. Analysis of the DNA
      mismatch repair-associated PMS2 gene, which overlaps at the genomic level with
      the JTV-1 gene, revealed PMS2 mRNA to be down-regulated in tumor spheroids, which
      was confirmed at the protein level. Analysis of PMS2(-/-) mouse embryo
      fibroblasts confirmed a role for PMS2 in sensitivity to cisplatin, and DNA
      mismatch repair activity was found to be reduced in EMT-6 spheroids compared to
      monolayers. Dominant negative PMS2 transfection caused increased resistance to
      cisplatin in EMT-6 and CHO cells. Our results implicate reduced DNA mismatch
      repair as a determinant factor of reversible multicellular resistance of tumor
      cells to alkylating agents.

PMID- 15254248
TI  - Cross talk between retinoic acid signaling and transcription factor GATA-2.
AB  - All-trans-retinoic acid (RA) stimulates differentiation of normal hematopoietic
      progenitors and acute myeloid leukemia cells. GATA-2 is a transcription factor
      expressed in early progenitor cells and implicated in the control of the fate of
      hematopoietic stem cells and progenitor cells. We have investigated the
      possibility that the GATA and nuclear hormone receptor pathways are functionally
      linked through direct protein-protein interaction. Here we demonstrate that in
      human myeloid KG1 cells, RA receptor alpha (RARalpha), the major RAR expressed in
      hematopoietic cells, associates with GATA-2. This association is mediated by the
      zinc fingers of GATA-2 and the DNA-binding domain of RARalpha. As a consequence
      of this interaction, RARalpha is tethered to the DNA sites that are recognized
      and bound by GATA-2, and the transcriptional activity of GATA-2 becomes RA
      responsive. The RA responsiveness of GATA-dependent transcription is eliminated
      by expression of either a dominant negative form of RARalpha or a GATA-2 mutant
      that fails to interact with RARalpha. Overexpression of RXRalpha inhibits
      RARalpha binding to the GATA-2-DNA complex, thus resulting in attenuation of the
      effects of RARalpha on GATA-2 activity. In addition, inhibition by RA of GATA-2
      dependent hematopoietic colony formation in an embryonic stem cell model of
      hematopoietic differentiation provided biological evidence for functional cross
      talk between RA and GATA-2-dependent pathways.

PMID- 15254250
TI  - DNA cleavage activity of the V(D)J recombination protein RAG1 is autoregulated.
AB  - RAG1 and RAG2 catalyze the first DNA cleavage steps in V(D)J recombination. We
      demonstrate that the isolated central domain of RAG1 has inherent single-stranded
      (ss) DNA cleavage activity, which does not require, but is enhanced by, RAG2. The
      central domain, therefore, contains the active-site residues necessary to perform
      hydrolysis of the DNA phosphodiester backbone. Furthermore, the catalytic
      activity of this domain on ss DNA is abolished by addition of the C-terminal
      domain of RAG1. The inhibitory effects of this latter domain are suppressed on
      substrates containing double-stranded (ds) DNA. Together, the activities of the
      reconstituted domains on ss versus mixed ds-ss DNA approximate the activity of
      intact RAG1 in the presence of RAG2. We propose how the combined actions of the
      RAG1 domains may function in V(D)J recombination and also in aberrant cleavage
      reactions that may lead to genomic instability in B and T lymphocytes.

PMID- 15254251
TI  - La autoantigen is necessary for optimal function of the poliovirus and hepatitis
      C virus internal ribosome entry site in vivo and in vitro.
AB  - Translation of poliovirus and hepatitis C virus (HCV) RNAs is initiated by
      recruitment of 40S ribosomes to an internal ribosome entry site (IRES) in the
      mRNA 5' untranslated region. Translation initiation of these RNAs is stimulated
      by noncanonical initiation factors called IRES trans-activating factors (ITAFs).
      The La autoantigen is such an ITAF, but functional evidence for the role of La in
      poliovirus and HCV translation in vivo is lacking. Here, by two methods using
      small interfering RNA and a dominant-negative mutant of La, we demonstrate that
      depletion of La causes a dramatic reduction in poliovirus IRES function in vivo.
      We also show that 40S ribosomal subunit binding to HCV and poliovirus IRESs in
      vitro is inhibited by a dominant-negative form of La. These results provide
      strong evidence for a function of the La autoantigen in IRES-dependent
      translation and define the step of translation which is stimulated by La.

PMID- 15254252
TI  - A triad of subunits from the Gal11/tail domain of Srb mediator is an in vivo
      target of transcriptional activator Gcn4p.
AB  - The Srb mediator is an important transcriptional coactivator for Gcn4p in the
      yeast Saccharomyces cerevisiae. We show that three subunits of the Gal11/tail
      domain of mediator, Gal11p, Pgd1p, and Med2p, and the head domain subunit Srb2p
      make overlapping contributions to the interaction of mediator with recombinant
      Gcn4p in vitro. Each of these proteins, along with the tail subunit Sin4p, also
      contributes to the recruitment of mediator by Gcn4p to target promoters in vivo.
      We found that Gal11p, Med2p, and Pgd1p reside in a stable subcomplex in sin4Delta
      cells that interacts with Gcn4p in vitro and that is recruited independently of
      the rest of mediator by Gcn4p in vivo. Thus, the Gal11p/Med2p/Pgd1p triad is both
      necessary for recruitment of intact mediator and appears to be sufficient for
      recruitment by Gcn4p as a free subcomplex. The med2Delta mutation impairs the
      recruitment of TATA binding protein (TBP) and RNA polymerase II to the promoter
      and the induction of transcription at ARG1, demonstrating the importance of the
      tail domain for activation by Gcn4p in vivo. Even though the Gal11p/Med2p/Pgd1p
      triad is the only portion of Srb mediator recruited efficiently to the promoter
      in the sin4Delta strain, this mutant shows high-level TBP recruitment and wild
      type transcriptional induction at ARG1. Hence, the Gal11p/Med2p/Pgd1p triad may
      contribute to TBP recruitment independently of the rest of mediator.

PMID- 15254254
TI  - Evidence of selection on the domesticated ERVWE1 env retroviral element involved
      in placentation.
AB  - The human endogenous retrovirus HERV-W multicopy family includes a unique
      proviral locus, termed ERVWE1, which contains gag and pol pseudogenes and has
      retained a full-length envelope open reading frame (ORF). This Env protein
      (syncytin) is a highly fusogenic membrane glycoprotein and has been proposed to
      be involved in hominoid placental physiology. To track the hallmarks of natural
      selection acting on the ERVWE1 env gene, the pattern of substitutions and indels
      was analyzed within all human HERV-W elements and along the ERVWE1 orthologous
      loci in chimpanzee, gorilla, orangutan, and gibbon. The comparison of ERVWE1 and
      paralogous HERV-W copies revealed an ERVWE1-specific signature consisting of a
      four amino acid deletion in the intracytoplasmic tail of the glycoprotein. We
      show that this deletion is crucial for the envelope fusogenic activity. The
      comparison of the human ERVWE1 locus with its orthologs demonstrates the
      existence of a selective pressure to maintain the env reading frame open.
      Notably, the 3' part of the env gene, encoding regions required for the fusion
      process, is under purifying selection. The identification of selective
      constraints on env ERVWE1 confirms that this retroviral locus has been recruited
      in the hominoid lineage to become a bona fide gene.

PMID- 15254253
TI  - Preparation of DNA-modified nanoparticles and preliminary study for colorimetric
      SNP analysis using their selective aggregations.
AB  - DNA-modified nanospheres were prepared by anchoring amino-terminated
      oligodeoxynucleotides (ODNs) with carboxylates onto a colored polystyrene sphere
      surface through amido bonds. About 220 ODN molecules were immobilized onto a
      nanosphere 40 nm in diameter. Preliminary studies using the microspheres with 1
      microm diameter reveal that the specificity of hybridization was retained after
      modification. Three kinds of differently colored (RGB, red/green/blue)
      nanospheres bearing unique ODNs on their surface were prepared for detecting the
      p53 gene. Each ODN is complementary to a different part in the 45mer sample that
      is a part of a conservative region of the p53 gene containing one of the hot
      spots. In a binary system using spheres R and G, the wild-type 45mer made the
      aggregates with yellow emission as the result of mixing both colors. The mutant
      45mer containing one nucleotide displacement did not give such aggregates with
      distinct colors. The study of fluorescence resonance energy transfer (FRET)
      showed that spheres R and G directly contact each other in the aggregates with
      the wild type. The RGB ternary system gave aggregates with specific colors
      corresponding to the added ODN samples, wild type or mutant. In addition, in the
      presence of both samples, all of the spheres formed aggregates with white
      emission as a consequence of mixing three primary colors of light. This means
      that the present technique should allow us to conduct an allele analysis.

PMID- 15254255
TI  - Retroelement dynamics and a novel type of chordate retrovirus-like element in the
      miniature genome of the tunicate Oikopleura dioica.
AB  - Retrotransposable elements have played an important role in shaping eukaryotic
      DNA, and their activity and turnover rate directly influence the size of genomes.
      With approximately 15,000 genes within 65-75 megabases, the marine tunicate
      Oikopleura dioica, a nonvertebrate chordate, has the smallest and most compact
      genome ever found in animals. Consistent with a massive elimination of
      retroelements, only one apparently novel clade of non-long terminal repeat (non
      LTR) retrotransposons was detected within 41 megabases of nonredundant genomic
      sequences. In contrast, at least six clades of non-LTR elements were identified
      in the less compact genome of the tunicate Ciona intestinalis. Unexpectedly,
      Ty3/gypsy-related Tor LTR retrotransposons presented an astonishing level of
      diversity in O. dioica. They were generally poorly or apparently not corrupted,
      indicating recent activity. Both Tor3 and Tor4b families bore an envelope-like
      open reading frame, suggesting possible horizontal acquisition through infection.
      The Tor4b envelope-like gene might have been obtained from a paramyxovirus (RNA
      virus). Tor3 and Tor4b are phylogenetically clearly distinct from vertebrate
      retroviruses (Retroviridae) and are more reminiscent of certain insect and plant
      sequences. Tor elements potentially represent a so far unknown, ancient type of
      infectious retroelement in chordates. Their distribution and transmission
      dynamics in tunicates and other chordates deserve further study.

PMID- 15254256
TI  - PCR-induced sequence alterations hamper the typing of prehistoric bone samples
      for diagnostic achondroplasia mutations.
AB  - Achondroplasia (ACH) is a skeletal disorder (MIM100800) with an autosomal
      dominant Mendelian inheritance and complete penetrance. Here we report the
      screening of ancient bone samples for diagnostic ACH mutations. The diagnostic G-
      >A transition in the FGFR3 gene at cDNA position 1138 was detected in cloned
      polymerase chain reaction (PCR) products obtained from the dry mummy of the
      Semerchet tomb, Egypt (first dynasty, approximately 4,890-5,050 BP [before
      present]), and from an individual from Kirchheim, Germany (Merovingian period,
      approximately 1,300-1,500 BP), both of which had short stature. However, these
      mutations were also reproducibly observed in four ancient control samples from
      phenotypically healthy individuals (false-positives), rendering the reliable
      molecular typing of ancient bones for ACH impossible. The treatment of a false
      positive DNA extract with uracil N-glycosylase (UNG) to minimize type 2
      transitions (G-->A/C-->T) did not reduce the frequency of the false-positive
      diagnostic ACH mutations. Recently, it was suggested that ancient DNA extracts
      may induce mutations under PCR. Contemporary human template DNA from a
      phenotypically healthy individual was therefore spiked with an ancient DNA
      extract from a cave bear. Again, sequences with the diagnostic G-->A transition
      in the FGFR3 gene were observed, and it is likely that the false-positive G-->A
      transitions result from errors introduced during the PCR reaction. Amplifications
      in the presence of MnCl(2) indicate that position 1138 of the FGFR3 gene is
      particularly sensitive for mutations. Our data are in line with previously
      published results on the occurrence of nonrandom mutations in PCR products of
      contemporary human mitochondrial HVRI template DNA spiked with ancient DNA
      extracts.

PMID- 15254257
TI  - Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia.
AB  - It has been often stated that the overall pattern of human maternal lineages in
      Europe is largely uniform. Yet this uniformity may also result from an
      insufficient depth and width of the phylogenetic analysis, in particular of the
      predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of
      the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence
      information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes,
      from 11 European, Near and Middle Eastern, Central Asian, and Altaian
      populations. In addition to the seven previously specified subhaplogroups, we
      define fifteen novel subclades of Hg H present in the extant human populations of
      western Eurasia. The refinement of the phylogenetic resolution has allowed us to
      resolve a large number of homoplasies in phylogenetic trees of Hg H based on the
      first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125
      polymorphic positions in HVS-I were found to be mutated in more than one
      subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1*, H1b,
      H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct phylogeographic patterns. The
      monophyletic subhaplogroups of Hg H provide means for further progress in the
      understanding of the (pre)historic movements of women in Eurasia and for the
      understanding of the present-day genetic diversity of western Eurasians in
      general.

PMID- 15254258
TI  - NUPTs in sequenced eukaryotes and their genomic organization in relation to
      NUMTs.
AB  - NUPTs (nuclear plastid DNA) derive from plastid-to-nucleus DNA transfer and exist
      in various plant species. Experimental data imply that the DNA transfer is an
      ongoing, highly frequent process, but for the interspecific diversity of NUPTs,
      no clear explanation exists. Here, an inventory of NUPTs in the four sequenced
      plastid-bearing species and their genomic organization is presented. Large
      genomes with a predicted low gene density contain more NUPTs. In Chlamydomonas
      and Plasmodium, DNA transfer occurred but was limited, probably because of the
      presence of only one plastid per cell. In Arabidopsis and rice, NUPTs are
      frequently organized as clusters. Tight clusters can contain both NUPTs and NUMTs
      (nuclear mitochondrial DNA), indicating that preNUPTs and preNUMTs might have
      concatamerized before integration. The composition of such a hypothetical preNUPT
      preNUMT pool seems to be variable, as implied by substantially different
      NUPTs:NUMTs ratios in different species. Loose clusters can span several dozens
      of kbps of nuclear DNA, and they contain markedly more NUPTs or NUMTs than
      expected from a random genomic distribution of nuclear organellar DNA. The level
      of sequence similarity between NUPTs/NUMTs and plastid/mitochondrial DNA
      correlates with the size of the integrant. This implies that original insertions
      are large and decay over evolutionary time into smaller fragments with diverging
      sequences. We suggest that tight and loose clusters represent intermediates of
      this decay process.

PMID- 15254259
TI  - Bacteriophage flux in endosymbionts (Wolbachia): infection frequency, lateral
      transfer, and recombination rates.
AB  - The highly specialized genomes of bacterial endosymbionts typically lack one of
      the major contributors of genomic flux in the free-living microbial world
      bacteriophages. This study yields three results that show bacteriophages have, to
      the contrary, been influential in the genome evolution of the most prevalent
      bacterial endosymbiont of invertebrates, Wolbachia. First, we show that
      bacteriophage WO is more widespread in Wolbachia than previously recognized,
      occurring in at least 89% (35/39) of the sampled genomes. Second, we show through
      several phylogenetic approaches that bacteriophage WO underwent recent lateral
      transfers between Wolbachia bacteria that coinfect host cells in the dipteran
      Drosophila simulans and the hymenopteran Nasonia vitripennis. These two cases,
      along with a previous report in the lepidopteran Ephestia cautella, support a
      general mechanism for genetic exchange in endosymbionts--the "intracellular
      arena" hypothesis--in which genetic material moves horizontally between bacteria
      that coinfect the same intracellular environment. Third, we show recombination in
      this bacteriophage; in the region encoding a putative capsid protein, the
      recombination rate is faster than that of any known recombining genes in the
      endosymbiont genome. The combination of these three lines of genetic evidence
      indicates that this bacteriophage is a widespread source of genomic instability
      in the intracellular bacterium Wolbachia and potentially the invertebrate host.
      More generally, it is the first bacteriophage implicated in frequent lateral
      transfer between the genomes of bacterial endosymbionts. Gene transfer by
      bacteriophages could drive significant evolutionary change in the genomes of
      intracellular bacteria that are typically considered highly stable and prone to
      genomic degradation.

PMID- 15254260
TI  - Precision and accuracy of divergence time estimates from STR and SNPSTR
      variation.
AB  - Inference of intraspecific population divergence patterns typically requires
      genetic data for molecular markers with relatively high mutation rates.
      Microsatellites, or short tandem repeat (STR) polymorphisms, have proven
      informative in many such investigations. These markers are characterized,
      however, by high levels of homoplasy and varying mutational properties, often
      leading to inaccurate inference of population divergence. A SNPSTR is a genetic
      system that consists of an STR polymorphism closely linked (typically < 500 bp)
      to one or more single-nucleotide polymorphisms (SNPs). SNPSTR systems are
      characterized by lower levels of homoplasy than are STR loci. Divergence time
      estimates based on STR variation (on the derived SNP allele background) should,
      therefore, be more accurate and precise. We use coalescent-based simulations in
      the context of several models of demographic history to compare divergence time
      estimates based on SNPSTR haplotype frequencies and STR allele frequencies. We
      demonstrate that estimates of divergence time based on STR variation on the
      background of a derived SNP allele are more accurate (3% to 7% bias for SNPSTR
      versus 11% to 20% bias for STR) and more precise than STR-based estimates,
      conditional on a recent SNP mutation. These results hold even for models
      involving complex demographic scenarios with gene flow, population expansion, and
      population bottlenecks. Varying the timing of the mutation event generating the
      SNP revealed that estimates of divergence time are sensitive to SNP age, with
      more recent SNPs giving more accurate and precise estimates of divergence time.
      However, varying both mutational properties of STR loci and SNP age demonstrated
      that multiple independent SNPSTR systems provide less biased estimates of
      divergence time. Furthermore, the combination of estimates based separately on
      STR and SNPSTR variation provides insight into the age of the derived SNP
      alleles. In light of our simulations, we interpret estimates from data for human
      populations.

PMID- 15254261
TI  - Birth-and-death evolution with strong purifying selection in the histone H1
      multigene family and the origin of orphon H1 genes.
AB  - Histones are small basic nuclear proteins with critical structural and functional
      roles in eukaryotic genomes. The H1 multigene family constitutes a very
      interesting histone class gathering the greatest number of isoforms, with many
      different arrangements in the genome, including clustered and solitary genes, and
      showing replication-dependent (RD) or replication-independent (RI) expression
      patterns. The evolution of H1 histones has been classically explained by
      concerted evolution through a rapid process of interlocus recombination or gene
      conversion. Given such intriguing features, we have analyzed the long-term
      evolutionary pattern of the H1 multigene family through the evaluation of the
      relative importance of gene conversion, point mutation, and selection in
      generating and maintaining the different H1 subtypes. We have found the presence
      of an extensive silent nucleotide divergence, both within and between species,
      which is always significantly greater than the nonsilent variation, indicating
      that purifying selection is the major factor maintaining H1 protein homogeneity.
      The results obtained from phylogenetic analysis reveal that different H1 subtypes
      are no more closely related within than between species, as they cluster by type
      in the topologies, and that both RD and RI H1 variants follow the same
      evolutionary pattern. These findings suggest that H1 histones have not been
      subject to any significant effect of interlocus recombination or concerted
      evolution. However, the diversification of the H1 isoforms seems to be enhanced
      primarily by mutation and selection, where genes are subject to birth-and-death
      evolution with strong purifying selection at the protein level. This model is
      able to explain not only the generation and diversification of RD H1 isoforms but
      also the origin and long-term persistence of orphon RI H1 subtypes in the genome,
      something that is still unclear, assuming concerted evolution.

PMID- 15254262
TI  - Cross-talk of integrin alpha3beta1 and tissue factor in cell migration.
AB  - In cancer and angiogenesis, coagulation-independent roles of tissue factor (TF)
      in cell migration are incompletely understood. Immobilized anti-TF extracellular
      domain antibodies induce cell spreading, but this phenomenon is epitope specific
      and is not induced by anti-TF 5G9. Spreading on anti-TF is beta1 integrin
      dependent, indicating functional interactions of the TF extracellular domain 5G9
      epitope (a presumed integrin-binding site) and integrins. Recombinant TF
      extracellular domain supports adhesion of cells expressing alphavbeta3 or certain
      beta1 integrin heterodimers (alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta1,
      alpha9beta1) and adhesion is blocked by specific anti-integrin antibodies or
      mutations in the integrin ligand-binding site. Although several studies have
      linked TF to cell migration, we here demonstrate that TF specifically regulates
      alpha3beta1-dependent migration on laminin 5. Expression of TF suppresses
      alpha3beta1-dependent migration, but only when the TF cytoplasmic domain is not
      phosphorylated. Suppression of migration can be reversed by 5G9, presumably by
      disrupting integrin interaction, or by the protease ligand VIIa, known to induce
      PAR-2-dependent phosphorylation of TF. In both cases, release of alpha3beta1
      inhibition is prevented by mutation of critical phosphorylation sites in the TF
      cytoplasmic domain. Thus, TF influences integrin-mediated migration through
      cooperative intra- and extracellular interactions and phosphorylation regulates
      TF's function in cell motility.

PMID- 15254263
TI  - Cdc2 kinase-dependent disassembly of endoplasmic reticulum (ER) exit sites
      inhibits ER-to-Golgi vesicular transport during mitosis.
AB  - We observed the disassembly of endoplasmic reticulum (ER) exit sites (ERES) by
      confocal microscopy during mitosis in Chinese hamster ovary (CHO) cells by using
      Yip1A fused to green fluorescence protein (GFP) as a transmembrane marker of
      ERES. Photobleaching experiments revealed that Yip1A-GFP, which was restricted to
      the ERES during interphase, diffused throughout the ER network during mitosis.
      Next, we reconstituted mitotic disassembly of Yip1A-GFP-labeled ERES in
      streptolysin O-permeabilized CHO cells by using mitotic L5178Y cytosol. Using the
      ERES disassembly assay and the anterograde transport assay of GFP-tagged
      VSVGts045, we demonstrated that the phosphorylation of p47 by Cdc2 kinase
      regulates the disassembly of ERES and results in the specific inhibition of ER-to
      Golgi transport during mitosis.

PMID- 15254264
TI  - Importance of mitochondrial dynamics during meiosis and sporulation.
AB  - Opposing fission and fusion events maintain the yeast mitochondrial network. Six
      proteins regulate these membrane dynamics during mitotic growth-Dnm1p, Mdv1p, and
      Fis1p mediate fission; Fzo1p, Mgm1p, and Ugo1p mediate fusion. Previous studies
      established that mitochondria fragment and rejoin at distinct stages during
      meiosis and sporulation, suggesting that mitochondrial fission and fusion are
      required during this process. Here we report that strains defective for
      mitochondrial fission alone, or both fission and fusion, complete meiosis and
      sporulation. However, visualization of mitochondria in sporulating cultures
      reveals morphological defects associated with the loss of fusion and/or fission
      proteins. Specifically, mitochondria collapse to one side of the cell and fail to
      fragment during presporulation. In addition, mitochondria are not inherited
      equally by newly formed spores, and mitochondrial DNA nucleoid segregation
      defects give rise to spores lacking nucleoids. This nucleoid inheritance defect
      is correlated with an increase in petite spore colonies. Unexpectedly,
      mitochondria fragment in mature tetrads lacking fission proteins. The latter
      finding suggests either that novel fission machinery operates during sporulation
      or that mechanical forces generate the mitochondrial fragments observed in mature
      spores. These results provide evidence of fitness defects caused by fission
      mutations and reveal new phenotypes associated with fission and fusion mutations.

PMID- 15254265
TI  - NrCAM coupling to the cytoskeleton depends on multiple protein domains and
      partitioning into lipid rafts.
AB  - NrCAM is a cell adhesion molecule of the L1 family that is implicated in the
      control of axonal growth. Adhesive contacts may promote advance of the growth
      cone by triggering the coupling of membrane receptors with the F-actin retrograde
      flow. We sought to understand the mechanisms leading to clutching the F-actin at
      the site of ligand-mediated clustering of NrCAM. Using optical tweezers and
      single particle tracking of beads coated with the ligand TAG-1, we analyzed the
      mobility of NrCAM-deletion mutants transfected in a neuroblastoma cell line.
      Deletion of the cytoplasmic tail did not prevent the coupling of NrCAM to the
      actin flow. An additional deletion of the FNIII domains to remove cis
      interactions, was necessary to abolish the rearward movement of TAG-1 beads,
      which instead switched to a stationary behavior. Next, we showed that the actin
      dependent retrograde movement of NrCAM required partitioning into lipid rafts as
      indicated by cholesterol depletion experiments using methyl-beta-cyclodextrin.
      Recruitment of the raft component caveolin-1 was induced at the adhesive contact
      between the cell surface and TAG-1 beads, indicating that enlarged rafts were
      generated. Photobleaching experiments showed that the lateral mobility of NrCAM
      increased with raft dispersion in these contact areas, further suggesting that
      TAG-1-coated beads induced the coalescence of lipid rafts. In conclusion, we
      propose that anchoring of NrCAM with the retrograde actin flow can be triggered
      by adhesive contacts via cooperative processes including interactions with the
      cytoplasmic tail, formation of cis-complex via the FNIII repeats, and lipid raft
      aggregation.

PMID- 15254266
TI  - Enhanced membrane fusion in sterol-enriched vacuoles bypasses the Vrp1p
      requirement.
AB  - Organization of lipids into membrane microdomains is a vital mechanism of protein
      processing. Here we show that overexpression of ERG6, a gene involved in
      ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and
      enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not
      via more efficient sorting, but instead promotes increased kinetics of fusion
      subreactions. We initially isolated ERG6 as a suppressor of a vrp1Delta growth
      defect selective for vacuole function. VRP1 encodes verprolin, an actin-binding
      protein that colocalizes to vacuoles. The vrp1Delta mutant has fragmented
      vacuoles in vivo and isolated vacuoles do not fuse in vitro, indicative of a
      Vrp1p requirement for membrane fusion. ERG6 overexpression rescues vrp1Delta
      vacuole fusion in a cytosol-dependent manner. Cytosol prepared from the vrp1Delta
      strain remains active; therefore, cytosol is not resupplying Vrp1p. Las17p (Vrp1p
      functional partner) antibodies, which inhibit wild-type vacuole fusion, do not
      inhibit the fusion of vacuoles from the vrp1Delta-ERG6 overexpression strain.
      Vacuole-associated actin turnover is decreased in the vrp1Delta strain, but
      recovered by ERG6 overexpression linking sterol enrichment to actin remodeling.
      Therefore, the Vrp1p/Las17p requirement for membrane fusion is bypassed by
      increased sterols, which promotes actin remodeling as part the membrane fusion
      mechanism.

PMID- 15254268
TI  - Cell context-specific effects of the beta-tubulin glycylation domain on assembly
      and size of microtubular organelles.
AB  - Tubulin glycylation is a posttranslational modification found in cells with cilia
      or flagella. The ciliate Tetrahymena has glycylation on ciliary and cortical
      microtubules. We showed previously that mutating three glycylation sites on beta
      tubulin produces immotile 9 + 0 axonemes and inhibits cytokinesis. Here, we use
      an inducible glycylation domain mutation and epitope tagging to evaluate the
      potential of glycylation-deficient tubulin for assembly and maintenance of
      microtubular systems. In axonemes, the major defects, including lack of the
      central pair, occurred during assembly, and newly made cilia were abnormally
      short. The glycylation domain also was required for maintenance of the length of
      already assembled cilia. In contrast to the aberrant assembly of cilia, several
      types of cortical organelles showed an abnormally high number of microtubules in
      the same mutant cells. Thus, the consequences of deficiency in tubulin
      glycylation are organelle type specific and lead to either insufficient assembly
      (cilia) or excessive assembly (basal bodies and cortical microtubules). We
      suggest that the diverse functions of the beta-tubulin glycylation domain are
      executed by spatially restricted microtubule-associated proteins.

PMID- 15254267
TI  - Autocrine extracellular signal-regulated kinase (ERK) activation in normal human
      keratinocytes: metalloproteinase-mediated release of amphiregulin triggers
      signaling from ErbB1 to ERK.
AB  - ErbB signaling through extracellular signal-regulated kinase (ERK) has been
      implicated in regulating the expression of ErbB ligands in hyperproliferative
      skin disorders and wound healing. Here, we characterize the process of autocrine
      ERK activation in cultured normal human keratinocytes (NHKs) subjected to growth
      factor (GF) deprivation. Basal ERK phosphorylation was lower after 48 h than
      after 24 h of GF deprivation, and lowest at 30-60 min after an additional medium
      change. ERK phosphorylation was markedly increased by low concentrations of
      epidermal growth factor (EGF) (0.2-1 ng/ml) that provoked only a limited increase
      in ErbB1 tyrosine phosphorylation and internalization. Basal ErbB tyrosine
      phosphorylation and ERK phosphorylation were inhibited by two different ErbB
      receptor tyrosine kinase inhibitors, by the ErbB1-specific neutralizing
      monoclonal antibody 225 IgG, by two different metalloproteinase inhibitors, and
      by neutralizing antibodies against amphiregulin (AR). In contrast, these
      responses were unaffected by neutralizing antibodies against other ErbB1 ligands
      or the ErbB2 inhibitors geldanamycin and AG825. The time course of autocrine ERK
      phosphorylation correlated with the appearance of soluble AR, and two different
      metalloproteinase inhibitors blocked AR release. These results define an
      amphiregulin- and ErbB1-dependent mechanism by which autocrine ERK activation is
      maintained in NHKs, even when ErbB1 autophosphorylation and internalization are
      limited.

PMID- 15254269
TI  - The ArfGAP Glo3 is required for the generation of COPI vesicles.
AB  - The small GTPase Arf and coatomer (COPI) are required for the generation of
      retrograde transport vesicles. Arf activity is regulated by guanine exchange
      factors (ArfGEF) and GTPase-activating proteins (ArfGAPs). The ArfGAPs Gcs1 and
      Glo3 provide essential overlapping function for retrograde vesicular transport
      from the Golgi to the endoplasmic reticulum. We have identified Glo3 as a
      component of COPI vesicles. Furthermore, we find that a mutant version of the
      Glo3 protein exerts a negative effect on retrograde transport, even in the
      presence of the ArfGAP Gcs1. Finally, we present evidence supporting a role for
      ArfGAP protein in the generation of COPI retrograde transport vesicles.

PMID- 15254270
TI  - Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis,
      is dependent on RabGAP AS160.
AB  - Insulin maintains whole body blood glucose homeostasis, in part, by regulating
      the amount of the GLUT4 glucose transporter on the cell surface of fat and muscle
      cells. Insulin induces the redistribution of GLUT4 from intracellular
      compartments to the plasma membrane, by stimulating a large increase in
      exocytosis and a smaller inhibition of endocytosis. A considerable amount is
      known about the molecular events of insulin signaling and the complex itinerary
      of GLUT4 trafficking, but less is known about how insulin signaling is
      transmitted to GLUT4 trafficking. Here, we show that the AS160 RabGAP, a
      substrate of Akt, is required for insulin stimulation of GLUT4 exocytosis. A
      dominant-inhibitory mutant of AS160 blocks insulin stimulation of exocytosis at a
      step before the fusion of GLUT4-containing vesicles with the plasma membrane.
      This mutant, however, does not block insulin-induced inhibition of GLUT4
      endocytosis. These data support a model in which insulin signaling to the
      exocytosis machinery (AS160 dependent) is distinct from its signaling to the
      internalization machinery (AS160 independent).

PMID- 15254271
TI  - Specific inhibition of the E.coli RecBCD enzyme by Chi sequences in single
      stranded oligodeoxyribonucleotides.
AB  - RecBCD is an ATP-dependent helicase and exonuclease which generates 3' single
      stranded DNA (ssDNA) ends used by RecA for homologous recombination. The
      exonuclease activity is altered when RecBCD encounters a Chi sequence (5'
      GCTGGTGG-3') in double-stranded DNA (ds DNA), an event critical to the generation
      of the 3'-ssDNA. This study tests the effect of ssDNA oligonucleotides having a
      Chi sequence (Ch+) or a single base change that abolishes the Chi sequence
      (Chi(o)), on the enzymatic activities of RecBCD. Our results show that a 14 and a
      20mer with Chi+ in the center of the molecule inhibit the exonuclease and
      helicase activities of RecBCD to a greater extent than the corresponding Chi(o)
      oligonucleotides. Oligonucleotides with the Chi sequence at one end, or the Chi
      sequence alone in an 8mer, failed to show Chi-specific inhibition of RecBCD.
      Thus, Chi recognition requires that Chi be flanked by DNA at either end. Further
      experiments indicated that the oligonucleotides inhibit RecBCD from binding to
      its dsDNA substrate. These results suggest that a specific site for Chi
      recognition exists on RecBCD, which binds Chi with greater affinity than a non
      Chi sequence and is probably adjacent to non-specific DNA binding sites.

PMID- 15254272
TI  - Identification of a functional core in the RNA component of RNase MRP of budding
      yeasts.
AB  - RNase MRP is an endonuclease participating in ribosomal RNA processing. It
      consists of one RNA and at least nine protein subunits. Using oligonucleotide
      directed mutagenesis, we analyzed the functional role of five of the hairpins in
      the secondary structure of the RNA subunit of Saccharomyces cerevisiae RNase MRP.
      Deletion of an entire hairpin was either lethal or resulted in very poor growth.
      However, peripheral portions constituting up to 70% of a hairpin could be deleted
      without effects on cell growth rate or processing of rRNA. To determine whether
      these hairpins perform redundant functions, we analyzed mutants combining four or
      five benign hairpin deletions. Simultaneous removal of four of these hairpin
      segments had no detectable effect. Removing five created a temperature- and cold
      sensitive enzyme, but these deficiencies could be partially overcome by a
      mutation in one of the RNase MRP protein subunits, or by increasing the copy
      number of several of the protein subunit genes. These observations suggest that
      the peripheral elements of the RNA hairpins contain no structures or sequences
      required for substrate recognition, catalysis or binding of protein subunits.
      Thus, the functionally essential elements of the RNase MRP RNA appear to be
      concentrated in the core of the subunit.

PMID- 15254273
TI  - Biological consequences of oxidative stress-induced DNA damage in Saccharomyces
      cerevisiae.
AB  - Reactive oxygen species (ROS), generated by endogenous and exogenous sources,
      cause significant damage to macromolecules, including DNA. To determine the
      cellular effects of induced, oxidative DNA damage, we established a relationship
      between specific oxidative DNA damage levels and biological consequences produced
      by acute H2O2 exposures in yeast strains defective in one or two DNA damage
      handling pathways. We observed that unrepaired, spontaneous DNA damage interferes
      with the normal cellular response to exogenous oxidative stress. In addition,
      when base excision repair (BER) is compromised, there is a preference for using
      recombination (REC) over translesion synthesis (TLS) for handling H2O2-induced
      DNA damage. The global genome transcriptional response of these strains to
      exogenous H2O2 exposure allowed for the identification of genes responding
      specifically to induced, oxidative DNA damage. We also found that the presence of
      DNA damage alone was sufficient to cause an increase in intracellular ROS levels.
      These results, linking DNA damage and intracellular ROS production, may provide
      insight into the role of DNA damage in tumor progression and aging. To our
      knowledge, this is the first report establishing a relationship between H2O2
      induced biological endpoints and specific oxidative DNA damage levels present in
      the genome.

PMID- 15254274
TI  - Prevalence of intron gain over intron loss in the evolution of paralogous gene
      families.
AB  - The mechanisms and evolutionary dynamics of intron insertion and loss in
      eukaryotic genes remain poorly understood. Reconstruction of parsimonious
      scenarios of gene structure evolution in paralogous gene families in animals and
      plants revealed numerous gains and losses of introns. In all analyzed lineages,
      the number of acquired new introns was substantially greater than the number of
      lost ancestral introns. This trend held even for lineages in which vertical
      evolution of genes involved more intron losses than gains, suggesting that gene
      duplication boosts intron insertion. However, dating gene duplications and the
      associated intron gains and losses based on the molecular clock assumption showed
      that very few, if any, introns were gained during the last approximately 100
      million years of animal and plant evolution, in agreement with previous
      conclusions reached through analysis of orthologous gene sets. These results are
      generally compatible with the emerging notion of intensive insertion and loss of
      introns during transitional epochs in contrast to the relative quiet of the
      intervening evolutionary spans.

PMID- 15254275
TI  - Transcriptional regulation of the Drosophila caudal homeobox gene by DRE/DREF.
AB  - The caudal-related homeobox transcription factors are required for the normal
      development and differentiation of intestinal cells. Recent reports indicate that
      misregulation of homeotic gene expression is associated with gastrointestinal
      cancer in mammals. However, the molecular mechanisms that regulate expression of
      the caudal-related homeobox genes are poorly understood. In this study, we have
      identified a DNA replication-related element (DRE) in the 5' flanking region of
      the Drosophila caudal gene. Gel-mobility shift analysis reveals that three of the
      four DRE-related sequences in the caudal 5'-flanking region are recognized by the
      DRE-binding factor (DREF). Deletion and site-directed mutagenesis of these DRE
      sites results in a considerable reduction in caudal gene promoter activity.
      Analyses with transgenic flies carrying a caudal-lacZ fusion gene bearing wild
      type or mutant DRE sites indicate that the DRE sites are required for caudal
      expression in vivo. These findings indicate that DRE/DREF is a key regulator of
      Drosophila caudal homeobox gene expression and suggest that DREs and DREF
      contribute to intestinal development by regulating caudal gene expression.

PMID- 15254276
TI  - Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting
      cyclophilin A.
AB  - Human immunodeficiency virus 1 (HIV-1) multiplication depends on a cellular
      protein, cyclophilin A (CyPA), that gets integrated into viral particles. Because
      CyPA is not required for cell viability, we attempted to block its synthesis in
      order to inhibit HIV-1 replication. For this purpose, we used antisense U7 small
      nuclear RNAs (snRNAs) that disturb CyPA pre-mRNA splicing and short interfering
      RNAs (siRNAs) that target CyPA mRNA for degradation. With dual-specificity U7
      snRNAs targeting the 3' and 5' splice sites of CyPA exons 3 or 4, we obtained an
      efficient skipping of these exons and a strong reduction of CyPA protein.
      Furthermore, short interfering RNAs targeting two segments of the CyPA coding
      region strongly reduced CyPA mRNA and protein levels. Upon lentiviral vector
      mediated transduction, prolonged antisense effects were obtained for both types
      of antisense RNAs in the human T-cell line CEM-SS. These transduced CEM-SS cells
      showed a delayed, and for the siRNAs also reduced, HIV-1 multiplication. Since
      the two types of antisense RNAs function by different mechanisms, combining the
      two approaches may result in a synergistic effect.

PMID- 15254277
TI  - Embryo ethics--the moral logic of stem-cell research.

PMID- 15254278
TI  - Zygote and "clonote"--the ethical use of embryonic stem cells.

PMID- 15254279
TI  - The business of stem cells.

PMID- 15254280
TI  - "Medicine is my lawful wife"--Anton Chekhov, 1860-1904.

PMID- 15254281
TI  - Neoplastic angiogenesis--not all blood vessels are created equal.

PMID- 15254282
TI  - Timing and magnitude of increases in levothyroxine requirements during pregnancy
      in women with hypothyroidism.
AB  - BACKGROUND: Hypothyroidism during pregnancy has been associated with impaired
      cognitive development and increased fetal mortality. During pregnancy, maternal
      thyroid hormone requirements increase. Although it is known that women with
      hypothyroidism should increase their levothyroxine dose during pregnancy,
      biochemical hypothyroidism occurs in many. In this prospective study we attempted
      to identify precisely the timing and amount of levothyroxine adjustment required
      during pregnancy. METHODS: Women with hypothyroidism who were planning pregnancy
      were observed prospectively before and throughout their pregnancies. Thyroid
      function, human chorionic gonadotropin, and estradiol were measured before
      conception, approximately every two weeks during the first trimester, and monthly
      thereafter. The dose of levothyroxine was increased to maintain the thyrotropin
      concentration at preconception values throughout pregnancy. RESULTS: Twenty
      pregnancies occurred in 19 women and resulted in 17 full-term births. An increase
      in the levothyroxine dose was necessary during 17 pregnancies. The mean
      levothyroxine requirement increased 47 percent during the first half of pregnancy
      (median onset of increase, eight weeks of gestation) and plateaued by week 16.
      This increased dose was required until delivery. CONCLUSIONS: Levothyroxine
      requirements increase as early as the fifth week of gestation. Given the
      importance of maternal euthyroidism for normal fetal cognitive development, we
      propose that women with hypothyroidism increase their levothyroxine dose by
      approximately 30 percent as soon as pregnancy is confirmed. Thereafter, serum
      thyrotropin levels should be monitored and the levothyroxine dose adjusted
      accordingly.

PMID- 15254283
TI  - Lymphoma-specific genetic aberrations in microvascular endothelial cells in B
      cell lymphomas.
AB  - BACKGROUND: The growth of most tumors depends on the formation of new blood
      vessels. In contrast to genetically unstable tumor cells, the endothelial cells
      of tumor vessels are considered to be normal diploid cells that do not acquire
      mutations. METHODS: Using a combined immunohistochemical and fluorescence in situ
      hybridization assay, we examined the endothelial cells in 27 B-cell lymphomas for
      cytogenetic alterations that are known to be present in the lymphoma cells.
      RESULTS: We found that 15 to 85 percent (median, 37 percent) of the microvascular
      endothelial cells in the B-cell lymphomas harbored lymphoma-specific chromosomal
      translocations. In addition, numerical chromosomal aberrations were shared by the
      lymphoma cells and the endothelial cells. CONCLUSIONS: Our findings suggest that
      microvascular endothelial cells in B-cell lymphomas are in part tumor-related and
      therefore reflect a novel aspect of tumor angiogenesis.

PMID- 15254285
TI  - Clinical practice. Treatment of deep-vein thrombosis.

PMID- 15254284
TI  - Mannose-binding lectin variant alleles and the risk of arterial thrombosis in
      systemic lupus erythematosus.
AB  - BACKGROUND: Cardiovascular disease is an important complication in patients with
      systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin
      gene are associated with SLE as well as with severe atherosclerosis. We
      determined whether mannose-binding lectin variant alleles were associated with an
      increased risk of arterial thrombosis among patients with SLE. METHODS: Mannose
      binding lectin alleles were genotyped by means of a polymerase-chain-reaction
      assay in 91 Danish patients with SLE. Arterial and venous thromboses occurring
      after the diagnosis of SLE were assessed in a prospective study. Arterial and
      venous thromboses were confirmed by appropriate diagnostic methods. RESULTS:
      Fifty-four patients had no mannose-binding lectin variant alleles (A/A genotype),
      30 were heterozygous (A/O genotype), and 7 were homozygous (O/O genotype). During
      a median follow-up of 9.1 years, arterial thromboses (cerebral or myocardial
      infarction or leg embolus) developed in 6 of the 7 patients with the O/O
      genotype, as compared with 18 of the 84 patients with the other two genotypes
      (hazard ratio, 5.8; 95 percent confidence interval, 2.2 to 15.2; overall
      incidence, 26 percent). After correction for other known risk factors, the hazard
      ratio was 7.0 (95 percent confidence interval, 1.9 to 25.4). Venous thromboses,
      which occurred in 14 patients, were statistically unrelated to the mannose
      binding lectin genotype. CONCLUSIONS: Among patients with SLE, homozygosity for
      mannose-binding lectin variant alleles is associated with an increased risk of
      arterial thrombosis. The risk of venous thrombosis is not increased, indicating
      that mannose-binding lectin has a specific role in providing protection against
      arterial thrombosis.

PMID- 15254286
TI  - Images in clinical medicine. Henoch-Schonlein purpura.

PMID- 15254287
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 22-2004. A 30-year-old woman with a pericardial effusion.

PMID- 15254288
TI  - Increased levothyroxine requirements in pregnancy--why, when, and how much?

PMID- 15254289
TI  - C-reactive protein and coronary heart disease.

PMID- 15254290
TI  - Bioethics, science, and politics.

PMID- 15254291
TI  - Childhood vaccination and type 1 diabetes.

PMID- 15254292
TI  - Management of cirrhosis and ascites.

PMID- 15254293
TI  - Pediatric palliative care.

PMID- 15254294
TI  - Blue cohosh and perinatal stroke.

PMID- 15254295
TI  - Images in clinical medicine. Massive subcutaneous emphysema after tracheal
      perforation.

PMID- 15254296
TI  - Origin of the neighboring residue effect on peptide backbone conformation.
AB  - Unfolded peptides in water have some residual structure that may be important in
      the folding process, and the nature of the residual structure is currently of
      much interest. There is a neighboring residue effect on backbone conformation,
      discovered in 1997 from measurements of (3)J(HN alpha) coupling constants. The
      neighboring residue effect appears also in the "coil library" of Protein Data
      Bank structures of residues not in alpha-helix and not in beta-structure. When a
      neighboring residue (i - 1 or i + 1) belongs to class L (aromatic and beta
      branched amino acids, FHITVWY) rather than class S (all others, G and P
      excluded), then the backbone angle of residue i is more negative for essentially
      all amino acids. Calculated values of peptide solvation (electrostatic solvation
      free energy, ESF) predict basic properties of the neighboring residue effect. We
      show that L amino acids reduce the solvation of neighboring peptide groups more
      than S amino acids. When tripeptides from the coil library are excised to allow
      solvation, the central residues have more negative values of <phi> but less
      negative values of <ESF> with L than with S neighbors. The coil library values of
      <(3)J(HN alpha)>, which vary strikingly among the amino acids, are correlated
      with the neighboring residue effect seen by ESF. Moreover, values for the
      "blocking effect" of side chains on the hydrogen exchange rates of peptide NH
      protons are correlated with ESF values.

PMID- 15254297
TI  - Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1
      phosphate.
AB  - Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that is involved in
      diverse biological functions. Local administration of S1P causes inflammation
      coupled to a large eosinophil (EO) recruitment in the rat-paw tissue. The
      inflammatory response is accompanied by an increase in S1P receptors, namely
      S1P(1), S1P(2), S1P(3), and by an enhanced expression of CCR3, which is the main
      chemokine receptor known to be involved in EO function. Human EOs constitutively
      express S1P(1) and, at a lower extent, S1P(2), S1P(3) receptors. S1P in vitro
      causes cultured human EO migration and an increase in S1P receptor mRNA copies
      and strongly up-regulates CCR3 and RANTES (regulated on activation, normal T cell
      expressed and secreted) message levels; in particular CCR3 is up-regulated 18,000
      fold by S1P. A blocking anti-CCR3 Ab inhibits S1P-induced chemotaxis, implying
      that S1P acts as specific recruiting signal for EOs not only through its own
      receptors but also through CCR3. These results show that S1P is involved in EO
      chemotaxis and contribute to shed light on the complex mechanisms underlying EO
      recruitment in several diseases such as asthma and some malignancies.

PMID- 15254298
TI  - Sampling design for an integrated socioeconomic and ecological survey by using
      satellite remote sensing and ordination.
AB  - Environmental variability is an important risk factor in rural agricultural
      communities. Testing models requires empirical sampling that generates data that
      are representative in both economic and ecological domains. Detrended
      correspondence analysis of satellite remote sensing data were used to design an
      effective low-cost sampling protocol for a field study to create an integrated
      socioeconomic and ecological database when no prior information on ecology of the
      survey area existed. We stratified the sample for the selection of tambons from
      various preselected provinces in Thailand based on factor analysis of spectral
      land-cover classes derived from satellite data. We conducted the survey for the
      sampled villages in the chosen tambons. The resulting data capture interesting
      variations in soil productivity and in the timing of good and bad years, which a
      purely random sample would likely have missed. Thus, this database will allow
      tests of hypotheses concerning the effect of credit on productivity, the sharing
      of idiosyncratic risks, and the economic influence of environmental variability.

PMID- 15254299
TI  - Structural and kinetic studies on ligand binding in wild-type and active-site
      mutants of penicillin acylase.
AB  - Penicillin acylase catalyses the condensation of Calpha-substituted phenylacetic
      acids with beta-lactam nucleophiles, producing semi-synthetic beta-lactam
      antibiotics. For efficient synthesis a low affinity for phenylacetic acid and a
      high affinity for Calpha-substituted phenylacetic acid derivatives is desirable.
      We made three active site mutants, alphaF146Y, betaF24A and alphaF146Y/betaF24A,
      which all had a 2- to 10-fold higher affinity for Calpha-substituted compounds
      than wild-type enzyme. In addition, betaF24A had a 20-fold reduced affinity for
      phenylacetic acid. The molecular basis of the improved properties was
      investigated by X-ray crystallography. These studies showed that the higher
      affinity of alphaF146Y for (R)-alpha-methylphenylacetic acid can be explained by
      van der Waals interactions between alphaY146:OH and the Calpha-substituent. The
      betaF24A mutation causes an opening of the phenylacetic acid binding site. Only
      (R)-alpha-methylphenylacetic acid, but not phenylacetic acid, induces a
      conformation with the ligand tightly bound, explaining the weak binding of
      phenylacetic acid. A comparison of the betaF24A structure with other open
      conformations of penicillin acylase showed that betaF24 has a fixed position,
      whereas alphaF146 acts as a flexible lid on the binding site and reorients its
      position to achieve optimal substrate binding.

PMID- 15254300
TI  - Severe acute respiratory syndrome (SARS): epidemiology and clinical features.
AB  - Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease
      with a significant morbidity and mortality. The major clinical features include
      persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and
      dyspnoea. Older subjects may present without the typical febrile response. Common
      laboratory features include lymphopenia, thrombocytopenia, raised alanine
      transaminases, lactate dehydrogenase, and creatine kinase. The constellation of
      compatible clinical and laboratory findings, together with certain characteristic
      radiological features and lack of clinical response to broad spectrum
      antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real
      time reverse transcriptase-polymerase chain reaction technique has a detection
      rate of 75%-80% in the first week of the illness.

PMID- 15254301
TI  - Scabies: more than just an irritation.
AB  - Human scabies, caused by skin infestation with the arthropod mite, Sarcoptes
      scabiei, typically results in a papular, intensely pruritic eruption involving
      the interdigital spaces, and flexure creases. Recent research has led to a
      reassessment of the morbidity attributable to this parasite in endemic
      communities, particularly resulting from secondary skin sepsis and postinfective
      complications including glomerulonephritis. This has led to studies of the
      benefits of community based control programmes, and to concerns regarding the
      emergence of drug resistance when such strategies are employed. The renewed
      research interest into the biology of this infection has resulted in the
      application of molecular tools. This has established that canine and human
      scabies populations are genetically distinct, a finding with major implications
      for the formulation of public health control policies. Further research is needed
      to increase understanding of drug resistance, and to identify new drug targets
      and potential vaccine candidates.

PMID- 15254302
TI  - An approach to drug induced delirium in the elderly.
AB  - Drugs have been associated with the development of delirium in the elderly.
      Successful treatment of delirium depends on identifying the reversible
      contributing factors, and drugs are the most common reversible cause of delirium.
      Anticholinergic medications, benzodiazepines, and narcotics in high doses are
      common causes of drug induced delirium. This article provides an approach for
      clinicians to prevent, recognise, and manage drug induced delirium. It also
      reviews the mechanisms for this condition, especially the neurotransmitter
      imbalances involving acetylcholine, dopamine, and gamma aminobutyric acid and
      discusses the age related changes that may contribute to altered pharmacological
      effects which have a role in delirium. Specific interventions for high risk
      elderly with the goal of preventing drug induced delirium are discussed.

PMID- 15254303
TI  - Subclinical hyperthyroidism: to treat or not to treat?
AB  - Subclinical hyperthyroidism may be defined as the presence of free thyroxine and
      tri-iodothyronine levels within the reference range and a reduced serum thyroid
      stimulating hormone (TSH) level. In this review the prevalence of low TSH in the
      population and health consequences of subclinical hyperthyroidism, for example,
      effects on heart and bone mass, are discussed. Guidelines for treatment are
      given, based on expert opinion.

PMID- 15254304
TI  - Management of haematemesis and melaena.
AB  - Acute upper gastrointestinal bleeding is a common medical emergency which carries
      hospital mortality in excess of 10%. The most important causes are peptic ulcer
      and varices. Varices are treated by endoscopic band ligation or injection
      sclerotherapy and management of the underlying liver disease. Ulcers with major
      stigmata are treated by injection with dilute adrenaline, thrombin, or fibrin
      glue; application of heat using the heater probe, multipolar electrocoagulation,
      or Argon plasma coagulation; or endoclips. Intravenous omeprazole reduces the
      risk of re-bleeding in ulcer patients undergoing endoscopic therapy. Repeat
      endoscopic therapy or operative surgery are required if bleeding recurs.

PMID- 15254305
TI  - Iron deficiency anaemia in general practice: clinical outcomes over three years
      and factors influencing diagnostic investigations.
AB  - BACKGROUND: Iron deficiency anaemia (IDA) may be a sign of significant
      gastrointestinal disease, and delayed diagnosis may result in chronic morbidity.
      Studies in patients referred to hospital for investigation of their anaemia have
      shown that 5%-15% have a gastrointestinal cancer but there are few studies of
      patients presenting to primary care. Factors influencing further investigation in
      these patients have not previously been identified. PATIENTS AND METHODS: A
      cohort of patients presenting to their general practitioners (GPs) with IDA was
      identified and clinical outcomes recorded. Logistic regression was used to
      determine which factors influenced GPs to investigate the anaemia. RESULTS: 43%
      of patients had investigations within three months and serious pathology was
      found in 30% of these; 13% of patients were considered unfit for further
      investigation and 8% refused to have any. Independent predictors of non
      investigation were a mild anaemia (odds ratio (OR) 0.38, confidence interval (CI)
      0.23 to 0.61, p<0.001), female gender (OR 0.49, CI 0.3 to 0.8, p = 0.004), a
      previous history of anaemia (OR 0.39, CI 0.24 to 0.64, p<0.001), and age <65
      years (OR 0.44, CI 0.26 to 0.74, p = 0.002). During the entire study period
      gastrointestinal cancer was diagnosed in 48 patients (11%); 17% of men had
      colorectal cancer. Of 263 patients alive at 12 months without a confirmed
      diagnosis, 113 (43%) had recurrent or persistent anaemia during the study period.
      CONCLUSION: Although the overall prevalence of gastrointestinal cancer in
      patients presenting to primary care is similar to that seen in secondary care,
      the diagnosis may be delayed due to lack of appropriate investigations resulting
      in significant morbidity.

PMID- 15254306
TI  - Non-clinical factors influencing the selection of patients with acute coronary
      syndromes for angiography.
AB  - OBJECTIVE: To analyse clinical and non-clinical factors determining the selection
      for coronary angiography in patients with acute coronary syndromes (ACS). DESIGN:
      Single centre, prospective cohort study. PARTICIPANTS: Eighty consecutive
      patients admitted with a diagnosis of ACS during the period 21 May 2001 to 4 July
      2001. SETTING: Coronary care unit of a tertiary referral centre, the Manchester
      Royal Infirmary. DATA COLLECTION: Information concerning baseline patient
      characteristics, clinical presentation, and the selection for angiography was
      collected from the patient notes. DATA COLLECTION: Windows SPSS version 9.0 using
      cross tabulations with chi(2) estimation and binomial logistic regression
      analysis. MAIN OUTCOME MEASURE: Selection for angiography in ACS. RESULTS: Cross
      tabulations with chi(2) analysis and logistic regression analysis identified
      significant non-clinical factors predicting the use of angiography. Although
      clinical factors such as recurrent ischaemia (odds ratio 5.11) influenced the
      decision to undergo coronary angiography, non-clinical factors such as young age
      (odds ratio 6.88 for <65 years old), gender (odds ratio 3.81 for males),
      admission on a weekday (odds ratio 0.2488 for admission on the weekend), and
      consultant in charge (odds ratio 0.111 for consultant "2") independently
      predicted the use of angiography in ACS. CONCLUSION: The selection of patients
      for angiography in ACS is not based purely on clinical criteria. Awareness of the
      apparent sources of bias among clinical decision makers may improve management of
      these patients.

PMID- 15254307
TI  - Clinical guidelines online: do they improve compliance?
AB  - BACKGROUND: The introduction of intranet services in a district general hospital
      provided an opportunity to put evidence based national guidelines online to
      facilitate access and promote application of best practice in acute medical care.
      This study evaluated the effectiveness of this approach. METHOD: Local guidelines
      were made available online at ward terminals after they had been distributed in
      paper form. An interrupted time series design was used to evaluate the impact on
      compliance with three preselected guidelines, which addressed the management of
      suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This
      was supplemented by a qualitative assessment of the views of medical staff.
      RESULTS: There was a significant increase in the adherence to the guidelines for
      stroke when they were made available online, but this was not demonstrable for
      deep vein thrombosis or upper gastrointestinal bleeding. Qualitative interviews
      with junior medical staff and consultants after the study was completed revealed
      that there was confusion regarding the application of the guidelines for deep
      vein thrombosis and little active support from the gastroenterologists for the
      guidelines for upper gastrointestinal bleeding. The stroke guidelines were
      actively promoted by their author and widely supported. CONCLUSION: Making
      guidelines available online will not be effective unless they are actively
      promoted and represent a consensus view.

PMID- 15254308
TI  - Is virtual bronchoscopy useful for physicians practising in a district general
      hospital?
AB  - BACKGROUND: Virtual bronchoscopy software is now available to district general
      hospitals (DGHs). There is limited information on the clinical utility of virtual
      bronchoscopy and whether it offers any additional information over conventional
      axial computed tomography in the setting of a busy DGH chest unit. METHODS:
      Virtual bronchoscopy and computed tomography findings were compared in all
      patients who had a virtual bronchoscopy study over a 12 month period. RESULTS:
      Eighteen consecutive patients had virtual bronchoscopy for a specific clinical
      indication over the study period. Additional information was conveyed by virtual
      bronchoscopy in five patients (in four patients the airways distal to an
      obstruction were better visualised thereby influencing decisions about airway
      stenting and in one patient the virtual bronchoscopy study showed an
      endobronchial lesion missed on computed tomography). In nine patients who were
      unfit for fibreoptic bronchoscopy (FOB) the radiologist was more confident in
      excluding an obstructive airway lesion. The main indication for performing a
      virtual bronchoscopy study was to rule out an obstructive airway lesion in
      patients who were unfit for FOB (n = 11). CONCLUSION: Virtual bronchoscopy is
      feasible and useful in the management of a few selected patients in a DGH chest
      unit. Virtual bronchoscopy may convey additional information over computed
      tomography when the distal airways need to be visualised and for discrete
      endoluminal lesions.

PMID- 15254309
TI  - Role of intravenous urogram in investigation of urinary tract infection: an
      observational study.
AB  - OBJECTIVES: To examine the value of an intravenous urogram (i.v.U) in patients
      with abnormal differential (99m)Tc dimercaptosuccinic acid (DMSA) uptake without
      scarring or ultrasound abnormality. STUDY DESIGN: Forty patients (age 0-19 years)
      were identified over a two year period in whom the differential renal uptake was
      >10%, who had smooth renal outlines, and had no evidence of scarring. All
      patients had an ultrasound examination. Two had marked urological abnormalities
      on ultrasound and eight had a duplex system in the kidney with greater DMSA
      uptake. In 18 patients where no explanation was apparent for the discrepant DMSA
      uptake, an i.v.U was performed. RESULTS: Eight patients had a normal i.v.U. In
      the remaining 10 patients, six had duplex systems without scarring and four had
      appearances of scarring in the kidney with reduced DMSA uptake. CONCLUSIONS: In
      this small selected group an i.v.U will identify a significant number of patients
      with normal kidneys, unrecognised simple duplex systems, or scarring where the
      DMSA scan has been inconclusive. This will help in planning long term follow up.

PMID- 15254310
TI  - Caring for "incurables": the 150th anniversary of the Royal Hospital for Neuro
      Disability, Putney.
AB  - The Royal Hospital for Incurables (RHI), now known as the Royal Hospital for
      Neuro-Disability and situated on West Hill, Putney, was founded by Andrew Reed DD
      exactly 150 years ago. The RHI was thus the pioneer in modern times of long stay
      institutions for the sick and dying. It became one of the great Victorian
      charities, and remained independent of the National Health Service, which was
      introduced in 1948. Originally the long stay patients suffered from a
      multiplicity of diseases; in recent years chronic neurological disease has
      dominated the scenario. This institution has also become a major centre for
      genetic and trauma-associated neurological damage, and rehabilitation.

PMID- 15254311
TI  - An unusual case of hirsutism.

PMID- 15254312
TI  - Evaluation of intermittent capture in a patient who has undergone an urgent
      temporary transvenous pacemaker lead insertion.

PMID- 15254313
TI  - Adolescent girl with back pain.

PMID- 15254314
TI  - Charcot's foot: advanced manifestation of diabetic neuropathy.

PMID- 15254315
TI  - Opposites detract.

PMID- 15254316
TI  - Long in the tooth.

PMID- 15254317
TI  - Resveratrol to the rescue.

PMID- 15254318
TI  - Sex-specific effects of interventions that extend fly life span.
AB  - Genetic and environmental interventions that extend life span are a current focus
      in research on the biology of aging. Most of this work has focused on differences
      among genotypes and species. A recent study on fruit flies shows that life span
      extension because of dietary restriction can be highly sex-specific. Here we
      review the literature on sex-specific effects of 56 genetic and 41 environmental
      interventions that extend life span in Drosophila melanogaster. We found that
      only one-sixth of the experiments provided statistical tests of differences in
      response between males and females, suggesting that sex-specific effects have
      been largely ignored. When measured, the life span extension was female-biased in
      8 of 16 cases, male-biased in 5 of 16 cases, and not significantly different in
      only 3 of 16 cases. We discuss possible explanations for the sex-specific
      differences and suggest various ways in which we might test these hypotheses. We
      argue that understanding sex differences in the response to life span-extending
      manipulations should lead to new insights about the basic mechanisms that
      underlie the biology of aging in both sexes.

PMID- 15254319
TI  - Industrial radiation processing--working behind the scenes.

PMID- 15254320
TI  - Experimental simulation of A-bomb gamma ray spectra: revisited.
AB  - It has been reported recently that the A-bomb gamma ray spectra received by the
      colon of the average Japanese survivor of Hiroshima and Nagasaki may be
      experimentally simulated using a hospital-based Philips SL15 linear accelerator.
      The simulated A-bomb gamma radiation may be used in radiobiology experiments to
      determine, amongst other things, the biological effectiveness of the A-bomb gamma
      radiation. However, in that study, the electron beams from the linear accelerator
      were poorly defined and photon contamination was ignored. In the study reported
      here, a Varian Clinac 2100C linear accelerator has been used for the same purpose
      but with photon contamination included in better defined output electron beams.
      It is found that the A-bomb gamma radiation can still be matched to an acceptable
      degree (<10%). The cause of the slightly poorer fit was due mainly to the
      different ranges of energies available from the linear accelerators used. The
      absorbed dose received by model breasts was also estimated in this study for the
      same situations as in the previous study. The ratio of the breast to colon doses
      was found to be only (3.9 +/- 4.0)% low compared with the expected values of 1.17
      and 1.16 for Hiroshima and Nagasaki, respectively. These results provide further
      confirmation of the acceptability of the simple cylindrically symmetrical body
      models employed in these studies to represent the average Japanese survivor.

PMID- 15254321
TI  - Options for the modified radiation weighting factor of neutrons.
AB  - The recent ICRP Report 92 has noted that the current radiation weighting factor,
      wR, depends on the energy of the incident neutrons in a manner that differs
      substantially from the dependence, which results from the current convention, QL.
      At all neutron energies, but most conspicuously below 1 MeV, the values of wR
      exceed those of the effective quality factor, qE. The discrepancy is largely due
      to the fact that--in the absence of computed values of the effective quality
      factor for neutrons--wR has been patterned after the values of the ambient
      quality factor, which accounts insufficiently for the low-linear energy transfer
      (LET) gamma ray component from neutron capture in the human body. There are
      different options to remove the discrepancy. Option 1 is to reduce wR
      substantially at all neutron energies to make it equal to qE for a standard
      condition, such as isotropic incidence of the neutrons. Since such a reduction
      may cause problems in those countries where the current wR values are already
      legally implemented, ICRP 92 has proposed what is here termed Option 2. It
      recommended to replace QL by the increased value 1.6 QL - 0.6 and, accordingly,
      to make the radiation weighting factor equal to 1.6 qE - 0.6. With Option 2 the
      radiation weighting factor needs to be decreased appreciably at low neutron
      energies, but for fission neutron spectra the overall changes are minor. To guide
      -regardless which option is chosen--the selection of the numerical values, the
      effective quality factor, qE, is computed here for different directional
      distributions of neutrons incident on the anthropomorphic phantoms ADAM and EVA.
      None of the sex averaged numerical values is found to deviate much from those for
      isotropic incidence. Isotropic incidence can, thus, be used as an adequate
      standard condition. A numerical approximation is proposed for the standard qE
      that is nearly equivalent to a formula invoked by ICRP 92, but is somewhat
      simpler and provides realistic values of qE even for the extremely high neutron
      energies in space. In line with ICRP 92, it is emphasised that wR needs to be
      seen as a derived quantity related to the LET-dependent weighting factor.

PMID- 15254322
TI  - Shielding analysis of the Microtron MT-25 bunker using the MCNP-4C code and NCRP
      Report 51.
AB  - A cyclic electron accelerator Microtron MT-25 will be installed in Havana, Cuba.
      Electrons, neutrons and gamma radiation up to 25 MeV can be produced in the MT
      25. A detailed shielding analysis for the bunker is carried out using two ways:
      the NCRP-51 Report and the Monte Carlo Method (MCNP-4C Code). The walls and
      ceiling thicknesses are estimated with dose constraints of 0.5 and 20 mSv y(-1),
      respectively, and an area occupancy factor of 1/16. Both results are compared and
      a preliminary bunker design is shown.

PMID- 15254323
TI  - Influence of variability of 214Pb recoil factor on lung dose.
AB  - Different parameters enter models of the human respiratory tract. The unattached
      fraction of the radon progeny was identified as the most important parameter,
      with the strongest influence on lung dose. The unattached fraction depends on the
      indoor aerosol concentration and other environmental conditions. The recoil
      factor, p, which influences the unattached fraction of 214Pb and 214Bi, defined
      as the average detachment probability from the aerosol after an alpha decay of
      218Po, has almost always been taken as a constant. Here the recoil factor was
      recalculated under different assumptions and found to be in the range between 0.1
      and 0.8. A smaller recoil factor means lower unattached fractions of 214Pb and
      214Bi. The influence of the recoil factor on lung dose was also estimated. The
      lung dose is smaller by about 10% if p = 0.1 is assumed in calculating the
      unattached fraction instead of p = 0.8.

PMID- 15254324
TI  - Task-specific monitoring of nuclear medicine technologists' radiation exposure.
AB  - Many studies have demonstrated that the exposure of nuclear medicine
      technologists arises primarily from radioactive patients rather than from
      preparation of radiopharmaceuticals. However, in order to devise strategies to
      reduce staff exposure, it is necessary to identify the specific tasks within each
      procedure that result in the highest radiation doses. An ESM Eberline FH41B-10
      radiation dosemeter, which records the ambient dose equivalent rate, was used to
      monitor the radiation exposure of a technologist and to record the dose rate in
      microSv per hour every 32 s throughout a working day. The technologist recorded
      the procedures that were being performed so that the procedures that resulted in
      higher doses could be identified clearly. The measured doses clearly showed that
      the major contributions to the technologist's dose were the following: (1)
      transferring incapacitated patients from the imaging table to a hospital trolley;
      (2) difficult injections without syringe shields; and (3) setting up patients for
      gated myocardial scans. The average dose to the technologist from transferring
      patients after a bone scan was 0.54 microSv, 40% of the total dose of 1.3 microSv
      for the complete bone scan procedure. The average dose received injecting 900 MBq
      of 99Tcm-HDP using a tungsten syringe shield was 0.57microSv, but the highest
      dose was 1.6 microSv, in a patient in whom the injection was difficult. A 0.5 mm
      lead apron was found to reduce the dose when setting up a patient for a gated
      stress 99Tcm-sestamibi myocardial scan by approximately a factor of 2. The
      average dose per patient for this task was reduced from 1.1 to 0.6 microSv. It is
      recommended that staff waiting for assistance with patient transfers stand away
      from the patient, that tungsten syringe shields be used for all
      radiopharmaceutical injections and that a 0.5 mm lead apron be worn when
      attending patients containing high activities of 99Tcm radiopharmaceuticals, such
      as those having myocardial imaging.

PMID- 15254325
TI  - Radiation exposure by radio-diagnostics in Switzerland: a pilot patient-oriented
      survey.
AB  - A patient-oriented survey was conducted in Switzerland with the aim to
      establishing the distribution of medical X-ray examinations among the population.
      A sample of 1235 people aged between 15 and 74 y (589 males and 637 females) was
      contacted. The participants were asked to give the number of medical X-ray
      examinations performed during the previous 12 months. Three-fourths of the sample
      did not undergo any medical X-ray examination during a 12 month-period, and 10%
      of the population underwent more than 1 medical X-ray examination in a year.
      These results were independent of the geographic region. The age distributions of
      the participants who did not undergo any medical X-ray examination and those who
      underwent one medical X-ray examination were similar. On the other hand, the age
      distribution of the participants who underwent more than one medical X-ray
      examination was characterised by a higher contribution from the elderly.

PMID- 15254326
TI  - A comprehensive study of natural gamma radioactivity levels and associated dose
      rates from surface soils in cyprus.
AB  - A survey was carried out to determine activity concentration levels and
      associated dose rates from the naturally occurring radionuclides 232Th, 238U and
      40K, in the various geological formations of Cyprus, by means of high-resolution
      gamma ray spectrometry. A total of 115 representative soil samples were collected
      from all over the bedrock surface of the island, based on the different
      lithological units of the study area, sieved through a fine mesh, sealed in 1000
      ml plastic Marinelli beakers and measured in the laboratory with respect to gamma
      radioactivity for a counting time of 18-h each. From the measured spectra,
      activity concentrations were determined for 232Th (range from 1.0 x 10(-2) to
      39.8 Bq kg(-1)), 238U (from 1.0 x 10(-2) to 39.3 Bq kg(-1)) and (40)K (from 4.0 x
      10(-2) to 565.8 Bq kg(-1)). Gamma absorbed dose rates in air outdoors were
      calculated to be in the range from 1.1 x 10(-2) to 51.3 nGy h(-1), depending on
      the geological features, with an overall mean value of 8.7 nGy h(-1) and a
      standard deviation of 8.4 nGy h(-1). This value is by a factor of about seven
      below the corresponding population-weighted world-averaged value of 60 nGy h(-1)
      and one of the lowest that has been reported from similar investigations
      worldwide. Assuming a 20% occupancy factor, the corresponding effective dose
      rates outdoors equivalent to the population were calculated to be between 1.3 x
      10(-2) and 62.9 microSv y(-1), with an arithmetic mean value of 10.7 microSv y(
      1) and a standard deviation of 10.3 microSv y(-1).

PMID- 15254327
TI  - Simulation of the experimental pre-dose technique for retrospective dosimetry in
      quartz.
AB  - The pre-dose technique of thermoluminescence for quartz has been used extensively
      for retrospective dosimetry of quartz and other natural materials. A recently
      published model that is a modification of the well-known Zimmerman theory is used
      here to simulate the complete sequence of experimental steps taken during the
      additive dose version of the pre-dose technique. The results of simulation show
      how the method can reproduce accurately the accumulated dose or paleodose
      received by the sample. The solution of the kinetic differential equations
      elucidates the various electron and hole processes taking place during the
      experimental pre-dose procedure and shows clearly the mechanism of hole transfer
      from the reservoir to the luminescence centre caused by heating to the activation
      temperature. The numerical results show that the pre-dose technique can reproduce
      the paleodose with an accuracy of +/- 1-5%, even when the paleodose is varied
      over more than an order of magnitude. New quantitative results are presented for
      the effect of the test dose and of the calibration beta dose, beta, on the
      accuracy of the pre-dose technique. The conclusions drawn from the simple model
      for quartz can be used to make improvements to more general quartz models.

PMID- 15254328
TI  - Development of software for internal dose calculation from bioassay measurements.
AB  - Recently developed biokinetic models of ICRP permit increasingly realistic
      descriptions of the behaviour of radionuclides in the human body. This, however,
      has made the interpretation of bioassay data extremely difficult. Thus computer
      programs for implementing these models are in need, but very few are available.
      The present work describes personal-computer-based software, MONDAL2 (monitoring
      to dose calculation ver. 2), that enables users to estimate intake activity and
      the resulting effective doses from bioassay measurements for both workers and
      members of the public. This software runs on Microsoft Windows 95, 98, Millennium
      edition, 2000 or XP. If the system is to be fully copied to a hard disk, hard
      disk space of 23 MB is required. This software is distributed by the National
      Institute of Radiological Sciences free of charge.

PMID- 15254329
TI  - Radiation doses to patients undergoing barium meal and barium enema examinations.
AB  - The radiation doses received by patients during 41 barium meal (BM) and 42 barium
      enema (BE) examinations in two Greek hospitals are presented. Radiation dose was
      measured in terms of the dose area product (DAP). The effective dose and doses to
      certain organs were estimated using the ODS-60 software. Mean total DAP values
      were found to be 25 +/- 11 Gy cm2 for BM and 60 +/- 35 Gy cm2 for BE
      examinations, whereas the estimated mean values of effective dose were 8.6 +/-
      4.0 and 24 +/- 16 mSv respectively. DAP to effective dose conversion coefficients
      were estimated to be 0.34 mSv per Gy cm2 for BM and 0.41 mSv per Gy cm2 for BE.

PMID- 15254330
TI  - A minimally invasive method to evaluate 131I kinetics in blood.
AB  - The dose limiting factor for 131I therapy in patients with thyroid cancer is
      myelotoxicity, thus an accurate determination of radioiodine activity in the red
      marrow is of paramount importance. The reference method for red marrow dosimetry
      in radiometabolic therapy is based on the measurement of radioiodine kinetics,
      particularly the activity/time curve in blood. Such a measurement requires
      withdrawal of blood samples at various times after 131I administration. This
      procedure involves some potential risk from the radiation protection point of
      view, such as possible contamination of personnel with blood and disposal of the
      radioactive blood samples (and syringes). We present here a minimally invasive
      method to evaluate radioiodine kinetics in the blood, which only requires one
      blood sample and a set of measurements on the patient's thigh made with a
      collimated NaI(Tl) probe. The method has been validated in four patients treated
      with 131I for thyroid cancer.

PMID- 15254331
TI  - The evaluation of parameters affecting accidents in companies using industrial
      radioactive sources in Iran.
AB  - More than 1000 radiation workers are engaged in about 70 private industrial
      radiography companies (IRCs) using 312 mobile gamma radiography devices (GRDs) in
      Iran. These companies mainly carry out radiography in open areas using 192Ir
      radioactive sources, ranging from 0.07 to 3 TBq (2-80 Ci). The radiation
      accidents that occurred in these companies led to acute radiation syndrome in 13
      workers and overexposure of 36 workers since 1998. The facilities and operating
      procedures of the Iranian private IRCs have been investigated during the past 5
      y. According to this study, in spite of the fact that most of the accidents were
      found to be due to the failure of critical components of GRDs, the main
      parameters affecting overexposures and deterministic effects were found to be
      incorrect or there was insufficient implementation of the monitoring programme,
      training and local rules in the IRCs.

PMID- 15254332
TI  - Dose limits for man do not adequately protect the ecosystem.
AB  - As has been noted by both of our participants, it is interesting to see that
      their views approached agreement during the course of the debate. This is not
      altogether unexpected since the topic is on that has many facets. It is fair to
      say that protecting man is an appropriate starting point for the protection of
      other more, or less, radiosensitive life forms sharing the planet with us. That
      there may be special situations requiring attention has been recognized by both
      of our participants. That the ICRP recognizes the need for further work on this
      topic is encouraging for ourselves as well as the 'bugs and bunnies'.

PMID- 15254333
TI  - Development of a peptide reactivity assay for screening contact allergens.
AB  - Allergic contact dermatitis resulting from skin sensitization is a common
      occupational and environmental health problem. In recent years, the local lymph
      node assay (LLNA) has emerged as a practical option for assessing the skin
      sensitization potential of chemicals. In addition to accurate identification of
      skin sensitizers, the LLNA can also provide a reliable measure of relative
      sensitization potency; information that is pivotal in successful management of
      human health risks. However, even with the significant animal welfare benefits
      provided by the LLNA, there is still interest in the development of nonanimal
      test methods for skin sensitization testing. One characteristic of a chemical
      allergen is its ability to react with proteins prior to the induction of skin
      sensitization. The majority of chemical allergens is electrophilic and as such
      reacts with nucleophilic amino acids like cysteine or lysine. In order to
      determine if reactivity correlates with sensitization potential, 38 chemicals
      representing allergens of different potencies (weak to extreme) and
      nonsensitizers were evaluated for their ability to react with glutathione or
      three synthetic peptides containing either cysteine, lysine, or histidine.
      Following a 15-min reaction time for glutathione or a 24 h reaction period for
      the three synthetic peptides, the samples were analyzed by HPLC. UV detection was
      used to monitor the depletion of glutathione or the peptide following reaction.
      The results demonstrate that a significant correlation (Spearman correlation)
      exists between allergen potency and the depletion of glutathione (p = 0.001),
      lysine (p = 0.025), and cysteine (p = 0.020), but not histidine. The peptide with
      the highest sensitivity was cysteine (80.8%) whereas histidine was the least
      sensitive (11.5%). The data presented show that measuring peptide reactivity has
      utility for screening chemicals for their skin sensitization potency and thus
      potential for reducing our reliance on animal test methods.

PMID- 15254334
TI  - Phytochemicals inhibit catechol-O-methyltransferase activity in cytosolic
      fractions from healthy human mammary tissues: implications for catechol estrogen
      induced DNA damage.
AB  - Phytochemicals are natural dietary constituents of fruits and vegetables. Some of
      these phytochemicals are known to affect estrogen-metabolizing enzymes. In breast
      tissue, estradiol can be metabolized to the catechol estrogens 2- and 4
      hydroxyestradiol (2-OHE(2) and 4-OHE(2)). Catechol estrogens are suspected
      carcinogens potentially involved in the etiology of breast cancer. Catechol-O
      methyltransferase (COMT) converts the catechol estrogens to their inactive
      methoxy derivatives (2-MeOE(2) and 4-MeOE(2)). In this study we investigated the
      effects of several phytochemicals on COMT activity in cytosolic fractions of
      seven healthy human mammary tissues from reduction mammoplasty. Large
      interindividual variations were observed in the constitutive levels of COMT
      activity. However, in all cytosol samples the catalytic efficiency of COMT was
      greater for 2-MeOE(2) formation than for 4-MeOE(2) formation. The known COMT
      inhibitor Ro 41-0960 and several phytochemicals with a catechol structure
      (quercetin, catechin, and (-)-epicatechin) concentration-dependently inhibited
      COMT activity, while phytochemicals without a catechol structure (genistein,
      chrysin, and flavone) showed no effect up to 30 microM. Distinct interindividual
      variations were observed in sensitivity toward COMT inhibition among the various
      tissue samples, as was shown by the range in IC(50) values for Ro 41-0960 (5-42
      nM). The toxicological relevance of COMT inhibition and the effect of reduced
      inactivation of catechol estrogens was studied by determining the amount of
      catechol estrogen-induced DNA damage in MCF-7 cells using the comet assay.
      Catechol estrogens alone caused no increase of DNA damage compared with control
      treated cells. However, both Ro 41-0960 and quercetin caused a decrease of
      methoxy estradiol formation and an increase of catechol estrogen-induced DNA
      damage in MCF-7 cells. This suggests that phytochemicals with a catechol
      structure have the potential to reduce COMT activity in mammary tissues and may
      consequently reduce the inactivation of potentially mutagenic estradiol
      metabolites and increase the chance of DNA damage.

PMID- 15254335
TI  - Continuous exposure to dibromoacetic acid delays pubertal development and
      compromises sperm quality in the rat.
AB  - Previously our work on the haloacid by-products of drinking water disinfection
      focused on adult exposures. Herein we evaluate the consequence of continuous
      exposure to dibromoacetic acid (DBA) via drinking water through reproductive
      development into adulthood. An initial study in which offspring were exposed from
      gestation day (GD) 15 through adulthood revealed significant delays in preputial
      separation and vaginal opening, dose-related decreases in the fertility of cauda
      epididymal sperm, and dose-related diminutions in the sperm membrane protein
      SP22. Subsequent studies consisted of groups in which exposure ceased on
      postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were
      evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to
      4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any
      significant reproductive alterations. By contrast, continuous exposure until
      adulthood resulted in dose-related alterations consistent with those observed in
      the dose-finding study. Preputial separation and vaginal opening were delayed 4
      and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was
      associated with increased responsiveness of both the testis and ovary to hCG ex
      vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56
      was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of
      proximal cauda epididymal sperm was compromised by continuous exposure to DBA.
      The sperm membrane proteome was altered in a dose-related manner with SP22, and
      one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As
      more sensitive endpoints are evaluated, lower effect levels can be attributed to
      haloacid exposure. We are now extending our evaluations to epidemiology studies
      designed to evaluate sperm quality in men exposed to varying levels of
      disinfection by-products.

PMID- 15254336
TI  - Haloacid induced alterations in fertility and the sperm biomarker SP22 in the rat
      are additive: validation of an ELISA.
AB  - Dibromoacetic acid (DBA) and bromochloroacetic acid (BCA) are prevalent
      disinfection by-products of drinking water that produce defects in
      spermatogenesis and fertility in adult rats. Previously we demonstrated that BCA
      compromises the fertility of cauda epididymal rat sperm and SP22, a sperm
      membrane protein that is highly correlated with the fertility of these sperm.
      Herein, we administered DBA and BCA, individually and in combination, to
      determine whether fertility and levels of SP22 on sperm were diminished in an
      additive fashion. Moreover, we wished to validate an immunoassay for quantitation
      of SP22. In a dose finding study, animals were exposed by oral gavage daily for
      14 days to: BCA alone at 1.6, 4, and 8 mg/kg; DBA at equimolar levels of 2, 5,
      and 10 mg/kg; and two binary mixtures of 1.6 mg/kg BCA + 2 mg/kg DBA and 4 mg/kg
      BCA + 5 mg/kg DBA. The ED(50)s for the decrease in SP22 quantified by two
      dimensional SDS-PAGE were 7.2 and 4.6 mg/kg for DBA and BCA. The ED(50)s for the
      decrease in SP22 quantified by ELISA were 8.1 and 5.9 mg/kg for DBA and BCA. The
      definitive study consisted of 2 and 4 mg/kg DBA, 1.6 and 3.2 mg/kg BCA, and a 2
      mg/kg DBA + 1.6 mg/kg BCA mixture. The ED(50)s for decreases in fertility
      assessed by intrauterine insemination were 3.5 mg/kg and 2.7 mg/kg for DBA and
      BCA. Immunolocalization of SP22 in spermatocytes and spermatids, as well as on
      the cytoplasmic droplet and the equatorial segment of luminal sperm, was
      decreased by the DBA + BCA mixture. The decrease in SP22 in testicular parenchyma
      was comparable to that observed for sperm extracts. Based on 2D SDS-PAGE, ELISA,
      or fertility the haloacid-induced decreases in SP22 or fertility were additive or
      synergistic. The correlation between SP22 levels by ELISA and fertility was r(2)
      = 0.72 compared to 0.82 for SP22 levels by 2D SDS-PAGE and fertility, validating
      SP22 quantitation by ELISA.

PMID- 15254337
TI  - Metabolic activation of 2,6-xylidine in the nasal olfactory mucosa and the mucosa
      of the upper alimentary and respiratory tracts in rats.
AB  - Whole-body low-temperature radioluminography of (3)H-2,6-xylidine in rats
      indicates that the nonmetabolized substance, which is a volatile and fat-soluble
      compound, is distributed throughout the body and accumulates in adipose tissues,
      e.g., in the abdominal and subcutaneous regions. Whole-body autoradiography with
      freeze-dried or solvent-extracted tissue sections as well as
      microautoradiography, which were used to trace tissues in the rats accumulating
      2,6-xylidine metabolites, showed presence of tissue-bound 2,6-xylidine
      metabolites in the nasal olfactory mucosa and the mucosa of the upper alimentary
      and respiratory tracts. These tissues were found to have an in vitro capacity to
      bioactivate 2,6-xylidine. Our data indicate that 2,6-xylidine in vivo undergoes
      an in situ bioactivation in these extrahepatic tissues. Our results showed that
      the nasal olfactory mucosa had a much higher capacity than the other examined
      tissues to bioactivate 2,6-xylidine. Thus, the carcinogenic effect of 2,6
      xylidine toward the nasal mucosa in rats is correlated with a high capacity of
      this tissue to bioactivate the compound.

PMID- 15254338
TI  - Chronic low-level mercury exposure, BDNF polymorphism, and associations with self
      reported symptoms and mood.
AB  - Recent reports have described neurobehavioral impairments in human subjects
      carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic
      factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with
      this BDNF polymorphism are similar to those observed among subjects with chronic
      exposure to elemental mercury (Hg degrees ), we examined the potential effect of
      this BDNF polymorphism on symptoms and mood in an established cohort of dental
      practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms
      and mood were obtained by computerized questionnaire from 193 male dentists (DTs)
      and 230 female dental assistants (DAs). Spot urine samples were analyzed for
      mercury concentrations to evaluate recent exposure. Detailed work histories were
      obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples
      were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current
      and 12 recent and chronic symptom groups, along with six mood factors, were
      evaluated with respect to recent and chronic Hg degrees exposure and BDNF
      polymorphism. Multiple regression analysis controlled for age, race,
      socioeconomic status, tobacco and alcohol use, self-reported health problems, and
      medications. Separate evaluations were conducted for DTs and DAs. Twenty-three
      associations between recent or chronic Hg degrees exposure and BDNF status and
      self-reported symptoms were observed with p < 0.10. All but three were in the
      expected direction (symptom scores increasing with Hg degrees exposure or BDNF
      polymorphism), and all but six were among DAs. All eight correlations between
      chronic exposure indices and recent and chronic symptoms among DAs were in the
      expected direction. All seven associations between BDNF and symptoms were in the
      expected direction and split between DTs and DAs. All three associations with
      mood factors were among DAs and in the expected direction. These results indicate
      that among DAs very low levels of occupational Hg degrees exposure are associated
      with increased symptoms. The BDNF polymorphism is also associated with increased
      symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive
      with respect to their associations with the same symptom group.

PMID- 15254339
TI  - Calcium-mediated activation of c-Jun NH2-terminal kinase (JNK) and apoptosis in
      response to cadmium in murine macrophages.
AB  - Cadmium is a well-known carcinogenic and immunotoxic metal commonly found in
      cigarette smoke and industrial effluent. An altered intracellular calcium
      ([Ca(2+)](i)) level has been implicated in the pathophysiology of immune
      dysfunction. The present study was designed to determine the possible involvement
      of calcium (Ca(2+)) and mitogen-activated protein kinases (MAPKs) signaling
      pathways on cadmium-induced cell death in J774A.1 murine macrophage cells.
      Cadmium caused a low-amplitude [Ca(2+)](i) elevation at 20 microM and rapid and
      high-amplitude [Ca(2+)](i) elevation at 500 microM. Exposure to cadmium dose
      dependently induced phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and
      deactivated p38 MAPK. Use of the selective JNK inhibitor SP600125 suggested that
      activation of JNK is pro-apoptotic and pro-necrotic. Buffering of the calcium
      response with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis
      (acetoxy-methyl) ester (BAPTA-AM) and ethylene glycol-bis-(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA) completely blocked cadmium-induced apoptotic
      response. The pretreatment of cells with BAPTA-AM and EGTA suppressed the cadmium
      induced cell injury, including growth arrest, mitochondrial activity impairment,
      and necrosis, and it also recovered the cadmium-altered JNK and p38 MAPK
      activity. Chelating [Ca(2+)](i) also reversed cadmium-induced hydrogen peroxide
      generation, suggesting that production of reactive oxygen species (ROS) is
      related to [Ca(2+)](i). The present study showed that cadmium induces a
      [Ca(2+)](i)-ROS-JNK-caspase-3 signaling pathway leading to apoptosis.
      Furthermore, cadmium-induced [Ca(2+)](i) regulates
      phosphorylation/dephosphorylation of JNK and p38, and it modulates signal
      transduction pathways to proliferation, mitochondrial activity, and necrosis.

PMID- 15254340
TI  - Dose-response modeling and benchmark calculations from spontaneous behavior data
      on mice neonatally exposed to 2,2',4,4',5-pentabromodiphenyl ether.
AB  - In this paper the benchmark dose (BMD) method was introduced for spontaneous
      behavior data observed in 2-, 5-, and 8-month-old male and female C57Bl mice
      exposed orally on postnatal day 10 to different doses of 2,2',4,4',5
      pentabromodiphenyl ether (PBDE 99). Spontaneous behavior (locomotion, rearing,
      and total activity) was in the present work quantified in terms of a fractional
      response defined as the cumulative response after 20 min divided by the
      cumulative response produced over the whole 1-h test period. The fractional
      response contains information about the time-response profile (which differs
      between the treatment groups) and has appropriate statistical characteristics. In
      the analysis, male and female mice could be characterized by a common dose
      response model (i.e., they responded equally to the exposure to PBDE 99). As a
      primary approach, the BMD was defined as the dose producing a 5 or 10% change in
      the mean fractional response. According to the Hill model, considering a 10%
      change the lower bound of the BMD for rearing, locomotion, and total activity was
      1.2, 0.85, and 0.31 mg PBDE 99/kg body weight, respectively. A probability-based
      procedure for BMD modeling was also considered. Using this methodology, the BMD
      was defined as corresponding to an excess risk of 5 or 10% of falling below
      cutoff points representing adverse levels of fractional response.

PMID- 15254341
TI  - Human respiratory tract cancer risks of inhaled formaldehyde: dose-response
      predictions derived from biologically-motivated computational modeling of a
      combined rodent and human dataset.
AB  - Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma
      (SCC) in F344 rats. The quantitative implications of the rat tumors for human
      cancer risk are of interest, since epidemiological studies have provided only
      equivocal evidence that formaldehyde is a human carcinogen. Conolly et al.
      (Toxicol. Sci. 75, 432-447, 2003) analyzed the rat tumor dose-response assuming
      that both DNA-reactive and cytotoxic effects of formaldehyde contribute to SCC
      development. The key elements of their approach were: (1) use of a three
      dimensional computer reconstruction of the rat nasal passages and computational
      fluid dynamics (CFD) modeling to predict regional dosimetry of formaldehyde; (2)
      association of the flux of formaldehyde into the nasal mucosa, as predicted by
      the CFD model, with formation of DNA-protein cross-links (DPX) and with
      cytolethality/regenerative cellular proliferation (CRCP); and (3) use of a two
      stage clonal growth model to link DPX and CRCP with tumor formation. With this
      structure, the prediction of the tumor dose response was extremely sensitive to
      cell kinetics. The raw dose-response data for CRCP are J-shaped, and use of these
      data led to a predicted J-shaped dose response for tumors, notwithstanding a
      concurrent low-dose-linear, directly mutagenic effect of formaldehyde mediated by
      DPX. In the present work the modeling approach used by Conolly et al. (ibid.) was
      extended to humans. Regional dosimetry predictions for the entire respiratory
      tract were obtained by merging a three-dimensional CFD model for the human nose
      with a one-dimensional typical path model for the lower respiratory tract. In
      other respects, the human model was structurally identical to the rat model. The
      predicted human dose response for DPX was obtained by scale-up of a computational
      model for DPX calibrated against rat and rhesus monkey data. The rat dose
      response for CRCP was used "as is" for the human model, since no preferable
      alternative was identified. Three sets of baseline parameter values for the human
      clonal growth model were obtained through separate calibrations against
      respiratory tract cancer incidence data for nonsmokers, smokers, and a mixed
      population of nonsmokers and smokers, respectively. Additional risks of
      respiratory tract cancer were predicted to be negative up to about one ppm for
      all three cases when the raw CRCP data from the rat were used. When a hockey
      stick-shaped model was fit to the rat CRCP data and used in place of the raw
      data, positive maximum likelihood estimates (MLE) of additional risk were
      obtained. These MLE estimates were lower, for some comparisons by as much as
      1,000-fold, than MLE estimates from previous cancer dose-response assessments for
      formaldehyde. Breathing rate variations associated with different physical
      activity levels did not make large changes in predicted additional risks. In
      summary, this analysis of the human implications of the rat SCC data indicates
      that (1) cancer risks associated with inhaled formaldehyde are de minimis (10(-6)
      or less) at relevant human exposure levels, and (2) protection from the noncancer
      effects of formaldehyde should be sufficient to protect from its potential
      carcinogenic effects.

PMID- 15254342
TI  - Developmental neurotoxicity of ketamine: morphometric confirmation, exposure
      parameters, and multiple fluorescent labeling of apoptotic neurons.
AB  - Ketamine is a widely used pediatric anesthetic recently reported (C. Ikonomidou
      et al., 1999, Science 283, 70-74) to enhance neuronal death in neonatal rats. To
      confirm and extend these results, we treated four groups of PND 7 rats with seven
      sc doses, one every 90 min, of either saline, 10 mg/kg ketamine, 20 mg/kg
      ketamine, or a single dose of 20 mg/kg ketamine. The repeated doses of 20 mg/kg
      ketamine increased the number of silver-positive (degenerating) neurons in the
      dorsolateral thalamus to a degree comparable to previous results (Ikonomidou et
      al., 1999, Science 283, 70-74), i.e., 28-fold vs. 31-fold respectively. However,
      blood levels of ketamine immediately after the repeated 20 mg/kg doses were about
      14 micrograms/ml, about seven-fold greater than anesthetic blood levels in humans
      (J. M. Malinovsky et al., 1996, Br. J. Anaesth. 77, 203-207; R. A. Mueller and R.
      Hunt, 1998, Pharmacol. Biochem. Behav. 60, 15-22). Levels of ketamine in blood
      following exposure to the multiple 10 mg/kg doses of ketamine or to a single 20
      mg/kg dose ranged around 2-5 micrograms/ml; although these blood levels are close
      to an anesthetic level in humans, they failed to produce neurodegeneration. To
      investigate the mode of ketamine-induced neuronal death, coronal sections were
      stained with both Fluoro-Jade B (a green fluorescent stain selective for
      neurodegeneration) and DAPI (a blue DNA stain), as well as for caspase-3 (using
      an antisera labeled red with rhodamine). These histochemical results confirmed
      the developmental neurotoxicity of ketamine, demonstrated that Fluoro-Jade B (FJ
      B), like silver methods, successfully stained degenerating neurons in neonatal
      rats, and indicated that ketamine acts by increasing the rate of neuronal
      apoptosis.

PMID- 15254343
TI  - A possible mechanism for decrease in serum thyroxine level by polychlorinated
      biphenyls in Wistar and Gunn rats.
AB  - We have previously demonstrated that in mice, the decrease in serum thyroxine
      (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in
      the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although
      the PCB-induced decrease in rats is generally thought to occur through induction
      of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the
      relationship between the decrease in serum T(4) level and the increase in UGT1A
      activity by PCB in rats, we examined the relationship using Wistar rats and Gunn
      rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total
      T(4) level was markedly decreased not only in the Wistar rats but also in the
      Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or
      2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no
      significant difference in magnitude of the decrease between the two rat strains.
      At the same time, the level and activity of T(4)-UDP-GT were significantly
      increased by treatment with either KC500 or PentaCB in Wistar rats but not in
      Gunn rats. In addition, no significant change in the level of serum total
      triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment
      was observed in either Wistar or Gunn rats. Furthermore, significant decrease in
      the activity of hepatic type-I deiodinase, which mediates the deiodization of
      T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and
      Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono
      and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum
      protein (transthyretin), were detected. In conclusion, the present results
      suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in
      Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The
      findings further suggest that the PCB-mediated decrease in serum T(4) level might
      occur, at least in part, through formation of the hydroxylated PCB metabolites.
      Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level
      might occur not only through the increase in hepatic T(4)-UDP-GT but also via
      formation of hydroxylated PCB metabolites.

PMID- 15254344
TI  - Tumor profile of novel p53 heterozygous Tg.AC (v-Ha-ras) bitransgenic mice
      treated with benzo(a)pyrene and fed dietary N-acetyl-L-cysteine (NAC).
AB  - We designed a novel short-term bitransgenic model to better characterize the
      effects of benzo(a)pyrene (BP) exposure on multi-organ carcinogenesis and to
      evaluate the effects of a well-recognized antioxidant, N-acetyl-L-cysteine (NAC),
      on neoplasia. We selected the p53 heterozygous Tg.AC (v-Ha-ras) mouse model for
      our studies because these mice possess a carcinogen-inducible ras oncogene and
      one functional p53 tumor suppressor allele. Both mutations occur frequently in
      human cancers. In a 2 x 2 experimental design, both female and male mice were fed
      basal diet alone or containing 3% NAC and administered by gavage corn oil vehicle
      alone or containing 20 mg BP/kg body weight given twice weekly for 10 weeks. Mice
      (n = 15 for each grouping and sex) were subsequently observed an additional 18
      weeks followed by tissue collection for evaluation of multi-organ pathology.
      Benzo(a)pyrene increased neoplasia in the thymus, spleen, stomach, and
      hematopoietic system after 28 weeks. We observed modest NAC-associated decreases
      in BP-induced pathology of the liver, papilloma formation and hyperplasia in the
      forestomach, and the occurrence of malignant lymphoma. Benzo(a)pyrene exposure
      reduced survival to approximately 40% in male mice, suggesting toxicity; however,
      survival in control groups was approximately 60%. Survival decreased to
      approximately 30% for females in all groups. We noted a clear, but
      nonsignificant, 15% decline in body weights of male, but not female, mice fed
      NAC, although food intake did not differ. Collectively, the data suggested
      carcinogen and antioxidant-associated effects on neoplasia that appeared sex
      dependent. Thus, this novel short-term bitransgenic model may potentially be
      useful for testing dietary modulation of carcinogenesis.

PMID- 15254345
TI  - Pharmacological prevention of post-ERCP pancreatitis: the facts and the fiction.

PMID- 15254346
TI  - Glucagonoma and pseudoglucagonoma syndrome.
AB  - CONTEXT: Glucagonoma syndrome may present either associated with a pancreatic
      neoplasm which secretes glucagon or as a pseudo-glucagonoma associated with other
      diseases. It is extremely infrequent but well-known with a current prevalence
      estimated at 1/20,000,000. DESIGN: A retrospective review of glucagonoma and
      pseudoglucagonoma cases observed between January 1998 and December 2003 in three
      hospitals. PATIENTS: Five cases: 3 with a demonstrable glucagon-secreting tumor
      and 2 cases without an associated neoplasm. MAIN OUTCOME MEASURES: Age, sex,
      initial diagnosis, associated symptoms, and pathology were analyzed as were
      procedures employed in diagnosis, imaging studies, laboratory data, surgery and
      follow-up. RESULTS: Hyperglycemia and elevated plasma glucagon levels were found
      in all cases. In 3 cases, hypo-aminoacidemia and a descrease in fatty acids were
      found. No changes of zinc levels were observed. Abdominal ultrasound studies were
      of no value except in evaluating pancreatitis. A CT-scan was conclusive when a
      pancreatic neoplasm existed and 3 patients were operated on a curative basis.
      DISCUSSION: Necrolytic migratory erythema was the key diagnosis in all cases.
      Surgery was intended to be curative. The follow-up was of 8, 37 and 57 months in
      the cases of true glucagonoma syndrome. CONCLUSIONS: A real prevalence of
      glucagonoma syndrome could be greater than currently estimated. In our series, it
      was 13.5/20,000,000. Pseudoglucagonoma syndrome remains a rarity.

PMID- 15254347
TI  - Diminished cellular immune response to carbonic anhydrase II in patients with
      Sjogren's syndrome and idiopathic chronic pancreatitis.
AB  - CONTEXT: A serum antibody to carbonic anhydrase II has been reported in patients
      with Sjogren's syndrome and idiopathic chronic pancreatitis. OBJECTIVE: To
      evaluate cellular immune response to carbonic anhydrase II in patients with
      Sjogren's syndrome and idiopathic chronic pancreatitis. PATIENTS: Idiopathic
      chronic pancreatitis (n=23), Sjogren's syndrome (n=12), alcoholic chronic
      pancreatitis (n=3) and normal controls (n=13). MAIN OUTCOME MEASURES:
      Proliferation assay of peripheral blood mononuclear cells. RESULTS: Notable
      increased proliferation of the mononuclear cells upon stimulation with carbonic
      anhydrase II was observed in 2 patients with idiopathic chronic pancreatitis (9%)
      and 2 patients with Sjogren's syndrome (17%) but not in patients with alcoholic
      chronic pancreatitis nor in normal controls. Among the four study groups, there
      was no significant difference in the prevalence rate of the positive
      proliferative responses (P=0.444). CONCLUSION: Carbonic anhydrase II may not be a
      major target antigen for the immunological process in the pathogenesis of
      Sjogren's syndrome and idiopathic chronic pancreatitis. Serum antibody to
      carbonic anhydrase II may be detected in these patients as a consequence of the
      immune reaction against other antigens which mimic carbonic anhydrase II.

PMID- 15254348
TI  - Effect of thyrotropin releasing hormone (TRH) on gene expressions in rat
      pancreas: approach by microarray hybridization.
AB  - CONTEXT: Thyrotropin releasing hormone (TRH), originally identified as a
      hypothalamic hormone, expresses in the pancreas. The effects of TRH such as,
      inhibiting amylase secretion in rats through a direct effect on acinar cells,
      enhancing basal glucagon secretion from isolated perfused rat pancreas, and
      potentiating glucose-stimulated insulin secretion in perfused rat islets and
      insulin-secreting clonal beta-cell lines, suggest that TRH may play a role in
      pancreas. TRH also enlarged pancreas and increased pancreatic DNA content but
      deletion of TRH gene expression caused hyperglycemia in mice, suggesting that TRH
      may play a critical role in pancreatic development; however, the biological
      mechanisms of TRH in the adult pancreas remains unclear. OBJECTIVES: This study
      explored the effect of TRH on rat pancreas. SUBJECTS: Four male-Sprague-Dawley
      rats (200-250 g) were given 10 microg/kg BW of TRH intraperitoneally on 1st and
      3rd day and sacrificed on 7th day. Four same-strain rats without TRH injection
      served as controls. MAIN OUTCOME MEASURES: Wet pancreatic weights were measured.
      Pancreatic tissues were homogenized and extracted. The insulin levels of the
      extracts were measured by ELISA. Total RNA from the pancreases were fluorescently
      labeled and hybridized to microarray with 1,081 spot genes. RESULTS: TRH
      increased pancreatic wet weight and insulin contents. About 75% of the 1,081
      genes were detected in the pancreas. TRH regulated up 99 genes and down 76 genes.
      The administration of TRH induced various types of gene expressions, such as G
      protein coupled receptors (GPCR) and signal transduction related genes (GPCR
      kinase 4, transducin beta subunit 5, arrestin beta1MAPK3, MAPK5, c-Src kinase,
      PKCs, PI3 kinase), growth factors (PDGF-B, IGF-2, IL-18, IGF-1, IL-2, IL-6,
      endothelin-1) and apoptotic factors (Bcl2, BAD, Bax). CONCLUSION: Reprogramming
      of transcriptome may be a way for TRH-regulation of pancreatic cellular
      functions.

PMID- 15254349
TI  - Tumor protein p53-induced nuclear protein 1 (TP53INP1) in spontaneous chronic
      pancreatitis in the WBN/Kob rat: drug effects on its expression in the pancreas.
AB  - CONTEXT: The tumor protein p53-induced nuclear protein 1 (TP53INP1) gene was
      found using DNA microarray technology as an overexpressed gene in acute
      pancreatitis. However, expression of TP53INP1 in chronic pancreatitis has not
      been previously reported. OBJECTIVE: This study investigated TP53INP1 gene
      expression and its relationship with p53 and apoptosis in spontaneous chronic
      pancreatitis in the Wistar-Bonn/Kobori rat. METHODS: Ninety four-week-old male
      Wistar-Bonn/Kobori rats were fed a special breeding diet until sacrifice.
      Camostat mesilate (n=30) or a herbal medicine (Saiko-keishi-to; n=30) were mixed
      with the diet, while the other 30 rats were untreated. The rats were sacrificed
      every 4 weeks for 20 weeks, and the pancreas was examined. In addition, 6 four
      week-old male Wistar-Bonn/Kobori rats were sacrificed and studied as starting
      reference. Finally, Wistar rats (n=36) were studied as controls. MAIN OUTCOME
      MEASURE: TP53INP1 mRNA expression was determined by reverse transcription
      polymerase chain reaction using semi-quantitative analysis, direct sequencing and
      in situ hybridization. RESULTS: TP53INP1 mRNA was strongly expressed at 12 weeks
      when chronic pancreatitis developed, with a second peak at 20 weeks. The
      expression kinetics of TP53INP1 mRNA paralleled acinar cell apoptosis assessed by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The p53
      mRNA expression showed a single peak at 12 weeks. In situ hybridization revealed
      that TP53INP1 mRNA was expressed mainly in acinar cells. Therapeutic drugs such
      as camostat mesilate and a herbal medicine Saiko-keishi-to suppressed the
      TP53INP1 mRNA expression. TP53INP1 mRNA induction in acinar cells was confirmed
      with in vitro experiments using an arginine-induced rat pancreatic acinar AR4-2J
      cell injury model. CONCLUSIONS: TP53INP1 expression may reflect the acute-phase
      response and apoptosis of acinar cells in the course of chronic pancreatitis.

PMID- 15254350
TI  - Pancreatic trauma from a book.
AB  - CONTEXT: An early diagnosis of pancreatic trauma can be challenging and difficult
      because of the lack of correlation between the initial presenting features,
      radiological and laboratory findings, and the severity of the trauma. A high
      degree of suspicion is essential to diagnose pancreatic injury particularly in
      patients with blunt trauma to the abdomen. A computerised tomography scan is
      useful in making an early diagnosis of pancreatic trauma, localizing the site of
      the injury and in the identification of main pancreatic duct injury which has
      major implications in the management of the patient. CASE REPORT: Here in, we
      report an interesting case of a 40-year-old woman who sustained a tear in the
      tail of the pancreas following a blunt injury to the pancreas while she was
      carrying a book in front of her abdomen and collided against an edge of a door
      frame. She was managed conservatively without any complications. CONCLUSIONS: A
      history of abdominal trauma, however trivial it may sound, needs to be
      appropriately investigated.

PMID- 15254351
TI  - Combined osteoclastic giant cell and pleomorphic giant cell tumor of the
      pancreas: a rarity. An immunohistochemical analysis and review of the literature.
AB  - CONTEXT: The combination of an osteoclastic giant cell tumor and a pleomorphic
      giant cell carcinoma of the pancreas is distinctly unusual and is associated with
      an adverse outcome. The origin of these two components within a tumor has long
      been debated based on the immunohistochemical and ultra-structural analysis. CASE
      REPORT: Herein we describe a tumor with amalgamation of these two distinct
      histomorphologies along with a minute focus of well-differentiated ductal
      adenocarcinoma (on multiple sections) in a 50-year male. On immunohistochemical
      analysis, osteoclastic giant cells were reactive for CD68 and vimentin confirming
      histiocytic/mesenchymal derivation whereas pleomorphic giant cells and
      mononuclear cells were reactive for cytokeratin which proved their epithelial
      nature. CONCLUSIONS: Although the present case had an equal proportion of both
      components, it is very important to correctly assess the predominant histology
      since osteoclastic giant cell tumor has a better prognosis as compared to the
      more aggressive pleomorphic giant cell carcinoma component.

PMID- 15254352
TI  - A wolf in sheep's clothing: a non-functioning islet cell tumor of the pancreas
      masquerading as a microcystic (serous cystic) adenoma.
AB  - CONTEXT: The endosonographic appearance of a microcystic "honeycomb" lesion of
      the pancreas usually indicates a serous cystic adenoma. CASE REPORT: We report a
      case of a non-functioning islet cell tumor that has the typical microcystic
      "honeycomb" appearance of a serous cystic adenoma. The implications for
      endoscopic ultrasound diagnosis and management of cystic pancreatic lesions are
      discussed. CONCLUSION: Islet cell tumors are a rare differential diagnosis of
      microcystic pancreatic lesions. If fine needle aspiration remains non-diagnostic
      preoperative distinction from serous cystic adenomas may be impossible.

PMID- 15254353
TI  - Recurrent acute pancreatitis in anorexia and bulimia.
AB  - CONTEXT: Mild pancreatitis has been reported as a consequence of anorexia
      nervosa, bulimia nervosa, or what has been termed the "dietary chaos syndrome".
      Either chronic malnutrition, or refeeding after periods of malnutrition, may
      precipitate acute pancreatitis through several pathogenetic mechanisms. CASE
      REPORT: A 26-year-old woman with a ten-year history of anorexia and bulimia
      presented with a third episode of acute pancreatitis in three months. The patient
      had been abstinent from alcohol for many years. Imaging studies during all three
      admissions failed to identify any biliary disease, including gallstones or
      biliary sludge. A cholecystectomy was performed, with a normal intraoperative
      cholangiogram, and no abnormalities on pathologic examination of the gallbladder
      and bile. The patient was discharged on hospital day 10 with no pain, and she has
      begun to return to regular eating habits. Pancreatitis has not recurred after 6
      months of follow up. We have identified 14 cases in the literature of acute
      pancreatitis associated with anorexia or bulimia. CONCLUSION: In the absence of
      evidence for gallstone, alcohol or metabolic etiologies, eating disorders may
      contribute to the pathophysiology of some idiopathic cases of pancreatitis.

PMID- 15254354
TI  - Intrasplenic pancreatic pseudocysts.

PMID- 15254355
TI  - Platelet aggregation, platelet serotonin and pancreatitis.

PMID- 15254357
TI  - Screening tests for pancreatic cancer: searching for the early symptoms or the
      population at risk.

PMID- 15254358
TI  - Endoscopic ultrasonography: impact in diagnosis, staging and management of
      pancreatic tumors. An overview.

PMID- 15254359
TI  - Pancreatic cancer imaging: which method?
AB  - Pancreatic cancer is the 10th most common malignancy and the 4th largest cancer
      killer in adults. Surgery offers the only chance of curing these patients.
      Complete surgical resection is associated with a 5-year survival rate of between
      20 and 30%. The challenge is how to best select those patients for curative
      surgery. Early studies demonstrated excellent sensitivity of EUS in detecting
      pancreatic tumors in comparison to CT. Similarly, EUS showed an 85-94% accuracy
      rate for T staging and 70-80% accuracy rate for N staging. Later studies report
      on substantially less TN staging accuracy for EUS. Possible explanations and the
      problem of vascular involvement assessment by EUS will be provided. Considering
      the role of EUS in M staging and a comparison between EUS, MRI, and positron
      emission tomography, scanning will be presented. A diagnostic algorithm for the
      evaluation of patients with a suspected pancreatic mass will be offered,
      stressing the pivotal role of EUS.

PMID- 15254360
TI  - Endosonographic evaluation of intraductal papillary mucinous tumors of the
      pancreas.

PMID- 15254361
TI  - Role of endoscopic ultrasonography in the diagnosis and treatment of cystic
      tumors of the pancreas.
AB  - Endoscopic ultrasound (EUS) allows high resolution imaging of the pancreas. EUS
      is a very useful technique for evaluating morphological features of a cystic
      tumors of the pancreas. These features include thick wall type, tumor protruding
      type, thick septal type, microcystic type, thin septal type and simple type.
      Malignant cystic lesions may present as a hypoechoic cystic/solid mass or as a
      complex cyst and are frequently associated with a dilated main pancreatic duct.
      There is some overlap between EUS appearances of non-neoplastic and neoplastic
      cystic pancreatic lesions. EUS guided FNA of cystic pancreatic lesions can play
      an important role in the differential diagnosis of these lesions and deciding
      about the need for surgery by evaluating cytology and tumor markers such as CEA
      in cyst fluid. There is some emerging data on EUS guided treatment of cystic
      pancreatic tumors by injection of alcohol.

PMID- 15254362
TI  - Endoscopic ultrasound and neuroendocrine tumours of the pancreas.

PMID- 15254363
TI  - Pancreatic fine needle aspiration: to do or not to do?

PMID- 15254364
TI  - Defining the diagnostic algorithm in pancreatic cancer.
AB  - Most patients with pancreatic cancer present with a mass on radiologic studies,
      however, not every pancreatic mass is cancer. Since radiological studies alone
      are insufficient to establish the diagnosis of a pancreatic mass and patient
      management depends on a definitive diagnosis; confirmatory cytology or histology
      is usually required. As a minimally invasive procedure, EUS and EUS FNA avoid the
      risk of cutaneous or peritoneal contamination that may occur with CT or US-guided
      investigations and is less invasive than surgical interventions. As a result, EUS
      FNA of pancreatic masses is becoming the standard for obtaining cytological
      diagnosis. This chapter presents an EUS-based diagnostic algorithm for the
      evaluation of pancreatic lesions and is based upon a review of the pertinent
      literature in the field of pancreatic endosonography that has been the most
      influential in helping to guide this evolving field. Realizing there is much
      overlap among the EUS characteristics of various pancreatic lesions, for the sake
      of simplicity we have structured our discussion in broad terms of solid versus
      cystic lesions and discuss various pancreatic lesions within this framework. The
      additional contributors to this round table discussion have been asked to provide
      a more dedicated, focused discussion of the various subcategories of pancreatic
      lesions in greater detail than we could hope to achieve here. We provide this
      final contribution to the round table as a means of bringing the discussion back
      to the big picture of pancreatic lesions, rather than trying to hone in on the
      fine details of any one subclass.

PMID- 15254365
TI  - Therapeutic endoscopic ultrasonography in pancreatic malignancy. Is the ERCP
      passe?

PMID- 15254366
TI  - Tumor destruction and in situ delivery of antigen presenting cells promote anti
      neoplastic immune responses: implications for the immunotherapy of pancreatic
      cancer.
AB  - Antigen presenting cells (APCs) activate helper and cytotoxic T cells specific
      for antigens expressed by tissue cells, including neoplastic cells. This event
      occurs after the antigen transfer from tissue cells to APC, and is referred to as
      "cross-presentation". The number and the state of activation of APC in the tumor
      control the outcome of cross-presentation, including the establishment of
      protective immune responses. Cell death favors cross-presentation. Cancer cells
      normally die, either spontaneously or as a consequence of targeted therapies. The
      transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the
      cross-presentation pathway, has the potential of yielding novel immunotherapeutic
      strategies. Their success will depend on at least two factors: the induction of
      synchronized cell death in the tumor, and the recruitment of activated dendritic
      cells in the tumor. Under normal conditions, pancreatic cancer represents a
      privileged environment; its profound chemoresistance reflects limited apoptosis
      after chemotherapy. Moreover, it usually contains only a few cells endowed with
      APC function. Endoscopic ultrasonography offers attractive possibilities of
      circumventing this privilege, including the delivery of ultrasound,
      radiofrequency or radiation in order to destroy the tumor and the delivery in
      situ of autologous APC or appropriate chemotactic signals. In general, loco
      regional approaches offer the possibility of using the tumor of each patient as a
      complex antigen source, thus limiting the risk of tumor escape and reducing the
      need for extensive ex vivo handling of the neoplasm and of the patient APCs.

PMID- 15254367
TI  - Celiac plexus neurolysis.

PMID- 15254368
TI  - Nuclear organization of centromeric domains is not perturbed by inhibition of
      histone deacetylases.
AB  - It is well established that modification of lysines in histone molecules
      correlates with gene expression and chromatin structure. It is not known whether
      this operates entirely at a local level, e.g. through the recruitment of specific
      proteins, or whether histone modifications might impact on more long-range
      aspects of chromatin organization. There is a distinctive organization of
      chromatin within the nucleus and the chromatin at the nuclear periphery of
      mammalian cells appears to be hypoacetylated. Previously it had been suggested
      that inhibition of histone deacetylases by TSA causes a gross remodeling of
      nuclear structure, specifically the recruitment of centromeric heterochromatin to
      the nuclear periphery. Here, we have quantified the nuclear organization of
      histone modifications and the localization of centromeric domains in human cells
      before and after TSA treatment. TSA alters the nuclear distribution of histone
      acetylation, but not that of histone methylation. TSA elevates levels of histone
      acetylation at the nuclear periphery but we see no alteration in the position of
      centromeric domains in the nuclei of treated cells. We conclude that the
      distinctive nuclear localization of centromeric domains is independent of histone
      acetylation.

PMID- 15254369
TI  - Occurrence of plant-uncoupling mitochondrial protein (PUMP) in diverse organs and
      tissues of several plants.
AB  - The presence of plant-uncoupling mitochondrial protein (PUMP), previously
      described by Vercesi et al. (1995), was screened in mitochondria of various
      organs or tissues of several plant species. This was done functionally, by
      monitoring purine nucleotide-sensitive linoleic acid-induced uncoupling, or by
      Western blots. The following findings were established: (1) PUMP was found in
      most of the higher plants tested; (2) since ATP inhibition of linoleic acid
      induced membrane potential decrease varied, PUMP content might differ in
      different plant tissues, as observed with mitochondria from maize roots, maize
      seeds, spinach leaves, wheat shoots, carrot roots, cauliflower, broccoli, maize
      shoots, turnip root, and potato calli. Western blots also indicated PUMP presence
      in oat shoots, carnation petals, onion bulbs, red beet root, green cabbage, and
      Sedum leaves. (3) PUMP was not detected in mushrooms. We conclude that PUMP is
      likely present in the mitochondria of organs and tissues of all higher plants.

PMID- 15254370
TI  - Functional characterization of the conserved "GLK" motif in mitochondrial porin
      from Neurospora crassa.
AB  - Mitochondrial porin facilitates the diffusion of small hydrophilic molecules
      across the mitochondrial outer membrane. Despite low sequence similarity among
      porins from different species, a "glycine-leucine-lysine" (GLK) motif is
      conserved in mitochondrial and Neisseria porins. To investigate the possible
      roles of these conserved residues, including their hypothesized participation in
      ATP binding by the protein, we replaced the lysine residue of the GLK motif of
      Neurospora crassa porin with glutamic acid through site-directed mutagenesis of
      the corresponding gene. Although the pores formed by this protein have size and
      gating characteristics similar to those of the wild-type protein, the channels
      formed by GLEporin are less anion selective than the wild-type pores. The
      GLEporin retains the ability to be cross linked to [alpha-(32)P]ATP, indicating
      that the GLK sequence is not essential for ATP binding. Furthermore, the pores
      formed by both GLEporin and the wild-type protein become more cation selective in
      the presence of ATP. Taken together, these results support structural models that
      place the GLK motif in a part of the ion-selective beta-barrel that is not
      directly involved in ATP binding.

PMID- 15254371
TI  - Modulation of the voltage-dependent anion channel (VDAC) by glutamate.
AB  - The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is
      a large channel permeable to anions, cations, ATP, and other metabolites. VDAC
      was purified from sheep brain synaptosomes or rat liver mitochondria using a
      reactive red-agarose column, in addition to the hydroxyapatitate column. The red
      agarose column allowed further purification (over 98%), concentration of the
      protein over ten-fold, decreasing Triton X-100 concentration, and/or replacing
      Triton X-100 with other detergents, such as Nonidet P-40 or octylglucoside. This
      purified VDAC reconstituted into planar-lipid bilayer, had a unitary maximal
      conductance of 3.7 +/- 0.1 nS in 1 M NaCl, at 10 mV and was permeable to both
      large cations and anions. In the maximal conducting state, the permeability
      ratios for Na(+), acetylcholine(+), dopamine,(+) and glutamate(-), relative to
      Cl(-), were estimated to be 0.73, 0.6, 0.44, and 0.4, respectively. In contrast,
      in the subconducting state, glutamate(-) was impermeable, while the relative
      permeability to acetylcholine(+) increased and to dopamine(+) remained unchanged.
      At the high concentrations (0.1-0.5 M) used in the permeability experiments,
      glutamate eliminated the bell shape of the voltage dependence of VDAC channel
      conductance. Glutamate at concentrations of 1 to 20 mM, in the presence of 1 M
      NaCl, was found to modulate the VDAC channel activity. In single-channel
      experiments, at low voltages (+/-10 mV), glutamate induced rapid fluctuations of
      the channel between the fully open state and long-lived low-conducting states or
      short-lived closed state. Glutamate modification of the channel activity, at low
      voltages, is dependent on voltage, requiring short-time (20-60 sec) exposure of
      the channel to high membrane potentials. The effect of glutamate is specific,
      since it was observed in the presence of 1 M NaCl and it was not obtained with
      aspartate or GABA. These results suggest that VDAC possesses a specific glutamate
      binding site that modulates its activity.

PMID- 15254372
TI  - Characterization of channel-forming activity in muscle biopsy from a porin
      deficient human patient.
AB  - A bioptic specimen from the muscles of a patient suffering from severe myopathy
      was inspected for the presence of human porin 31HL. Western blotting suggested
      that the specimen was free of the most abundant eukaryotic porin 31HL (HVDAC1).
      The specimen was treated with detergent and the soluble protein fraction was
      passed through a dry hydroxyapatite column. The passthrough of this column was
      inspected for channel formation in artificial lipid-bilayer membranes. The
      channel observed under these conditions had a single-channel conductance of about
      2.5 nS in 1 M KCl, was cation selective, and was found to be virtually voltage
      independent. Experiments with a control specimen from a healthy human being,
      without any indication for muscle myopathy, revealed the presence of the voltage
      dependent porin 31HL in the sample. It is discussed whether the patient's bioptic
      specimen contained another human porin, which has not been studied to date in its
      natural environment.

PMID- 15254373
TI  - Modulation at a distance of proton conductance through the Saccharomyces
      cerevisiae mitochondrial F1F0-ATP synthase by variants of the oligomycin
      sensitivity-conferring protein containing substitutions near the C-terminus.
AB  - We have sought to elucidate how the oligomycin sensitivity-conferring protein
      (OSCP) of the mitochondrial F(1)F(0)-ATP synthase (mtATPase) can influence proton
      channel function. Variants of OSCP, from the yeast Saccharomyces cerevisiae,
      having amino acid substitutions at a strictly conserved residue (Gly166) were
      expressed in place of normal OSCP. Cells expressing the OSCP variants were able
      to grow on nonfermentable substrates, albeit with some increase in generation
      time. Moreover, these strains exhibited increased sensitivity to oligomycin,
      suggestive of modification in functional interactions between the F(1) and F(0)
      sectors mediated by OSCP. Bioenergetic analysis of mitochondria from cells
      expressing OSCP variants indicated an increased respiratory rate under conditions
      of no net ATP synthesis. Using specific inhibitors of mtATPase, in conjunction
      with measurement of changes in mitochondrial transmembrane potential, it was
      revealed that this increased respiratory rate was a result of increased proton
      flux through the F(0) sector. This proton conductance, which is not coupled to
      phosphorylation, is exquisitely sensitive to inhibition by oligomycin.
      Nevertheless, the oxidative phosphorylation capacity of these mitochondria from
      cells expressing OSCP variants was no different to that of the control. These
      results suggest that the incorporation of OSCP variants into functional ATP
      synthase complexes can display effects in the control of proton flux through the
      F(0) sector, most likely mediated through altered protein-protein contacts within
      the enzyme complex. This conclusion is supported by data indicating impaired
      stability of solubilized mtATPase complexes that is not, however, reflected in
      the assembly of functional enzyme complexes in vivo. Given a location for OSCP
      atop the F(1)-alpha(3)beta(3) hexamer that is distant from the proton channel,
      then the modulation of proton flux by OSCP must occur "at a distance." We
      consider how subtle conformational changes in OSCP may be transmitted to F(0).

PMID- 15254374
TI  - Localization of the site of oxygen radical generation inside the complex I of
      heart and nonsynaptic brain mammalian mitochondria.
AB  - Mitochondrial production of oxygen radicals seems to be involved in many diseases
      and aging. Recent studies clearly showed that a substantial part of the free
      radical generation of rodent mitochondria comes from complex I. It is thus
      important to further localize the free radical generator site within this
      respiratory complex. In this study, superoxide production by heart and
      nonsynaptic brain submitochondrial particles from up to seven mammalian species,
      showing different longevities, were studied under different conditions. The
      results, taking together, show that rotenone stimulates NADH-supported superoxide
      generation, confirming that complex I is a source of oxygen radicals in mammals,
      in general. The rotenone-stimulated NADH-supported superoxide production of the
      heart and nonsynaptic brain mammalian submitochondrial particles was inhibited
      both by p-chloromercuribenzoate and by ethoxyformic anhydride. These results
      localize the complex I oxygen radical generator between the ferricyanide and the
      ubiquinone reduction site, making iron-sulfur centers possible candidates,
      although unstable semiquinones can not be discarded. The results also indicate
      that the previously described inverse correlation between rates of mitochondrial
      oxygen radical generation and mammalian longevity operates through mechanisms
      dependent on the presence of intact functional mitochondria.

PMID- 15254375
TI  - Evidence for a conformational change in subunit III of bovine heart mitochondrial
      cytochrome c oxidase.
AB  - The role of subunit III in the function of mitochondrial cytochrome c oxidase is
      not clearly understood. Previous work has shown that chemical modification of
      subunit III with N,N'-dicyclohexylcarbodiimide (DCCD) reduced the proton-pumping
      efficiency of the enzyme by an unknown mechanism. In the current work, we have
      employed biochemical approaches to determine if a conformational change is
      occurring within subunit III after DCCD modification. Control and DCCD modified
      beef heart enzyme were subjected to limited proteolysis in nondenaturing
      detergent solution. Subunit III in DCCD treated enzyme was more susceptible to
      chymotrypsin digestion than subunit III in the control enzyme. We also labeled
      control and DCCD-modified enzyme with iodoacetyl-biotin, a sulfhydryl reagent,
      and found that subunit III of the DCCD-modified enzyme was more reactive when
      compared to subunit III of the control enzyme, indicating an increase in
      reactivity of subunit III upon DCCD binding. The cross linking of subunit III of
      the enzyme induced by the heterobifunctional reagent, N-succinimidyl(4
      azidophenyl -1,3'-dithio)-propionate (SADP), was inhibited by DCCD modification,
      suggesting that DCCD binding prevents the intersubunit cross linking of subunit
      III. Our results suggest that DCCD modification of subunit III causes a
      conformational change, which most likely disrupts critical hydrogen bonds within
      the subunit and also those at the interface between subunits III and I in the
      enzyme. The conformational change induced in subunit III by covalent DCCD binding
      is the most likely mechanism for the previously observed inhibition of proton
      pumping activity.

PMID- 15254376
TI  - Proliferation of mitochondria in chronically stimulated rabbit skeletal muscle-
      transcription of mitochondrial genes and copy number of mitochondrial DNA.
AB  - Mitochondrial proliferation was studied in chronically stimulated rabbit skeletal
      muscle over a period of 50 days. After this time, subunits of COX had increased
      about fourfold. Corresponding mRNAs, encoded on mitochondrial DNA as well as on
      nuclear genes, were unchanged when related to total tissue RNA, however, they
      were elevated two- to fivefold when the massive increase of ribosomes per unit
      mass of muscle was taken into account. The same was true for the mRNA encoding
      mitochondrial transcription factor A. Surprisingly, tissue levels of mtTFA
      protein were reduced about twofold, together with mitochondrial DNA. In
      conclusion, mitochondria are able to maintain high rates of mitochondrial
      transcription even in the presence of reduced mtTFA protein and mtDNA levels.
      Therefore, stimulated mtTFA gene expression accompanies stimulated mitochondrial
      transcription, as in other models, but it is not sufficient for an increase of
      mtDNA copy number and other, yet unknown, factors have to be postulated.

PMID- 15254377
TI  - ATP synthases in the year 2000: defining the different levels of mechanism and
      getting a grip on each.
AB  - ATP synthases are unusually complex molecules, which fractionate most readily
      into two major units, one a water soluble unit called F(1) and the other a
      detergent soluble unit called F(0). In almost all known species the F(1) unit
      consists of 5 subunit types in the stoichiometric ratio
      alpha(3)beta(3)gammadeltaepsilon while the F(0) unit contains 3 subunit types (a,
      b, and c) in E. coli, and at least 10 subunit types (a, b, c, and others) in
      higher animals. It is now believed by many investigators that during the
      synthesis of ATP, protons derived from an electrochemical gradient generated by
      an electron transport chain are directed through the F(0) unit in such a way as
      to drive the rotation of the single gamma subunit, which extends from an
      oligomeric ring of at least 10 c subunits in F(0) through the center of F(1). It
      is further believed by many that the rotating gamma subunit, by interacting
      sequentially with the 3 alphabeta pairs of F(1) (360 degrees cycle) in the
      presence of ADP, P(i), and Mg++, brings about via "power strokes"
      conformational/binding changes in these subunits that promote the synthesis of
      ATP and its release on each alphabeta pair. In support of these views, studies in
      several laboratories either suggest or demonstrate that F(0) consists in part of
      a proton gradient driven motor while F(1) consists of an ATP hydrolysis driven
      motor, and that the gamma subunit does rotate during F(1) function. Therefore,
      current implications are that during ATP synthesis the former motor drives the
      latter in reverse via the gamma subunit. This would suggest that the process of
      understanding the mechanism of ATP synthases can be subdivided into three major
      levels, which include elucidating those chemical and/or biophysical events
      involved in (1) inducing rotation of the gamma subunit, (2) coupling rotation of
      this subunit to conformational/binding changes in each of the 3 alphabeta pairs,
      and (3) forming ATP and water (from ADP, P(i), and Mg(++)) and then releasing
      these products from each of the 3 catalytic sites. Significantly, it is at the
      final level of mechanism where the bond breaking/making events of ATP synthesis
      occur in the transition state, with the former two levels of mechanism setting
      the stage for this critical payoff event. Nevertheless, in order to get a better
      grip in this new century on how ATP synthases make ATP and then release it, we
      must take on the difficult challenge of elucidating each of the three levels of
      mechanism.

PMID- 15254378
TI  - The oligomeric subunit C rotor in the fo sector of ATP synthase: unresolved
      questions in our understanding of function.
AB  - We have proposed a model for the oligomeric c-rotor of the F(o) sector of ATP
      synthase and its interaction with subunit a during H+-transport driven rotation.
      The model is based upon the solution structure of monomeric subunit c, determined
      by NMR, and an extensive series of cross-linking distance constraints between c
      subunits and between subunits c and a. To explain the complete set of cross
      linking data, we have suggested that the second transmembrane helix rotates
      during its interaction with subunit a in the course of the H+-translocation
      cycle. The H+-transport coupled rotation of this helix is proposed to drive the
      stepwise movement of the c-oligomeric rotor. The model is testable and provides a
      useful framework for addressing questions raised by other experiments.

PMID- 15254379
TI  - A biological molecular motor, proton-translocating ATP synthase:
      multidisciplinary approach for a unique membrane enzyme.
AB  - Proton-translocating ATP synthase (F(o)F(1)) synthesizes ATP from ADP and
      phosphate, coupled with an electrochemical proton gradient across the biological
      membrane. It has been established that the rotation of a subunit assembly is an
      essential feature of the enzyme mechanism and that F(o)F(1) can be regarded as a
      molecular motor. Thus, experimentally, in the reverse direction (ATP hydrolysis),
      the chemical reaction drives the rotation of a gammaepsilonc(10-14) subunit
      assembly followed by proton translocation. We discuss our very recent results
      regarding subunit rotation in Escherichia coli F(o)F(1) with a combined
      biophysical and mutational approach.

PMID- 15254380
TI  - Osmomechanics of the Propionigenium modestum F(o) motor.
AB  - In Propionigenium modestum, ATP is manufactured from ADP and phosphate by the
      enzyme ATP synthase using the free energy of an electrochemical gradient of Na+
      ions. The P. modestum ATP synthase is a clear member of the family of F-type ATP
      synthases and the only major distinction is an extension of the coupling ion
      specificity to H+, Li+, or Na+, depending on the conditions. The use of Na+ as a
      coupling ion offers unique experimental options to decipher the ion-translocation
      mechanism and the osmotic and mechanical behavior of the enzyme. The single a
      subunit and the oligomer of c subunits are part of the stator and rotor,
      respectively, and operate together in the ion-translocation mechanism. During ATP
      synthesis, Na+ diffuses from the periplasm through the a subunit channel onto the
      Na+ binding site on a c subunit. From there it dissociates into the cytoplasm
      after the site has rotated out of the interface with subunit a. In the absence of
      a membrane potential, the rotor performs Brownian motions into either direction
      and Na+ ions are exchanged between the two compartments separated by the
      membrane. Upon applying voltage, however, the direction of Na+ flux and of
      rotation is biased by the potential. The motor generates torque to drive the
      rotation of the gamma subunit, thereby releasing tightly bound ATP from catalytic
      sites in F(1). Hence, the membrane potential plays a pivotal role in the torque
      generating mechanism. This is corroborated by the fact that for ATP synthesis, at
      physiological rates, the membrane potential is indispensable. We propose a
      catalytic mechanism for torque generation by the F(o) motor that is in accord
      with all experimental data and is in quantitative agreement with the requirement
      for ATP synthesis.

PMID- 15254381
TI  - Why is the mechanical efficiency of F(1)-ATPase so high?
AB  - The experimentally measured mechanical efficiency of the F(1)-ATPase under
      viscous loading is nearly 100%, far higher than any other hydrolysis-driven
      molecular motor (Yasuda et al., 1998). Here we give a molecular explanation for
      this remarkable property.

PMID- 15254382
TI  - The alpha/beta interfaces of alpha(1)beta(1), alpha(3)beta(3), and F1: domain
      motions and elastic energy stored during gamma rotation.
AB  - ATP synthase (F(o)F(1)) consists of F(1) (ATP-driven motor) and F(o) (H(+)-driven
      motor). F(1) is a complex of alpha(3)beta(3)gammadeltaepsilon subunits, and gamma
      is the rotating cam in alpha(3)beta(3). Thermophilic F(1) (TF(1)) is exceptional
      in that it can be crystallized as a beta monomer and an alpha(3)beta(3) oligomer,
      and it is sufficiently stable to allow alphabeta refolding and reassembly of
      hybrid complexes containing 1, 2, and 3 modified alpha or beta. The nucleotide
      dependent open-close conversion of conformation is an inherent property of an
      isolated beta and energy and signals are transferred through alpha/beta
      interfaces. The catalytic and noncatalytic interfaces of both mitochondrial F(1)
      (MF(1)) and TF(1) were analyzed by an atom search within the limits of 0.40 nm
      across the alphabeta interfaces. Seven (plus thermophilic loop in TF(1)) contact
      areas are located at both the catalytic and noncatalytic interfaces on the open
      beta form. The number of contact areas on closed beta increased to 11 and 9,
      respectively, in the catalytic and noncatalytic interfaces. The interfaces in the
      barrel domain are immobile. The torsional elastic strain applied through the
      mobile areas is concentrated in hinge residues and the P-loop in beta. The notion
      of elastic energy in F(o)F(1) has been revised. X-ray crystallography of F(1) is
      a static snap shot of one state and the elastic hypotheses are still inconsistent
      with the structure, dyamics, and kinetics of F(o)F(1). The domain motion and
      elastic energy in F(o)F(1) will be elucidated by time-resolved crystallography.

PMID- 15254383
TI  - What is the role of epsilon in the Escherichia coli ATP synthase?
AB  - The ATP synthase from Escherichia coli is a prototype of the ATP synthases that
      are found in many bacteria, in the mitochondria of eukaryotes, and in the
      chloroplasts of plants. It contains eight different types of subunits that have
      traditionally been divided into F(1), a water-soluble catalytic sector, and F(o),
      a membrane-bound ion transporting sector. In the current rotary model for ATP
      synthesis, the subunits can be divided into rotor and stator subunits. Several
      lines of evidence indicate that epsilon is one of the three rotor subunits, which
      rotate through 360 degrees. The three-dimensional structure of epsilon is known
      and its interactions with other subunits have been explored by several
      approaches. In light of recent work by our group and that of others, the role of
      epsilon in the ATP synthase from E. coli is discussed.

PMID- 15254384
TI  - Stoichiometry of energy coupling by proton-translocating ATPases: a history of
      variability.
AB  - One of the central energy-coupling reactions in living systems is the
      intraconversion of ATP with a transmembrane proton gradient, carried out by
      proton-translocating F- and V-type ATPases/synthases. These reversible enzymes
      can hydrolyze ATP and pump protons, or can use the energy of a transmembrane
      proton gradient to synthesize ATP from ADP and inorganic phosphate. The
      stoichiometry of these processes (H(+)/ATP, or coupling ratio) has been studied
      in many systems for many years, with no universally agreed upon solution. Recent
      discoveries concerning the structure of the ATPases, their assembly and the
      stoichiometry of their numerous subunits, particularly the proton-carrying
      proteolipid (subunit c) of the F(O) and V(0) sectors, have shed new light on this
      question and raise the possibility of variable coupling ratios modulated by
      variable proteolipid stoichiometries.

PMID- 15254385
TI  - Regulation of proton flow and ATP synthesis in chloroplasts.
AB  - The chloroplast ATP synthase is strictly regulated so that it is very active in
      the light (rates of ATP synthesis can be higher than 5 micromol/min/mg protein),
      but virtually inactive in the dark. The subunits of the catalytic portion of the
      ATP synthase involved in activation, as well as the effects of nucleotides are
      discussed. The relation of activation to proton flux through the ATP synthase and
      to changes in the structure of enzyme induced by the proton electrochemical
      gradient are also presented. It is concluded that the gamma and epsilon subunits
      of CF(1) play key roles in both regulation of activity and proton translocation.

PMID- 15254387
TI  - Notes on the mechanism of ATP synthesis.
AB  - The most commonly quoted mechanism of the coupling between the electrochemical
      proton gradient and the formation of ATP from ADP and P(i) assumes that all
      states of the F(1) portion of the ATP synthase have beta subunits in "tight,"
      "loose," and "open" conformations. Models based on this assumption are
      inconsistent with some of the available experimental evidence. A mechanism that
      includes an additional beta subunit conformation, "closed," observed in the rat
      liver structure overcomes these difficulties.

PMID- 15254386
TI  - The oligomycin axis of mitochondrial ATP synthase: OSCP and the proton channel.
AB  - Oligomycin has long been known as an inhibitor of mitochondrial ATP synthase,
      putatively binding the F(o) subunits 9 and 6 that contribute to proton channel
      function of the complex. As its name implies, OSCP is the oligomycin sensitivity
      conferring protein necessary for the intact enzyme complex to display sensitivity
      to oligomycin. Recent advances concerning the structure and mechanism of
      mitochondrial ATP synthase have led to OSCP now being considered a component of
      the peripheral stator stalk rather than a central stalk component. How OSCP
      confers oligomycin sensitivity on the enzyme is unknown, but probably reflects
      important protein-protein interactions made within the assembled complex and
      transmitted down the stator stalk, thereby influencing proton channel function.
      We review here our studies directed toward establishing the stoichiometry,
      assembly, and function of OSCP in the context of knowledge of the organization of
      the stator stalk and the proton channel.

PMID- 15254388
TI  - The catalytic transition state in ATP synthase.
AB  - The catalytic transition state of ATP synthase has been characterized and modeled
      by combined use of (1) Mg-ADP-fluoroaluminate, Mg-ADP-fluoroscandium, and
      corresponding Mg-IDP-fluorometals as transition-state analogs; (2) fluorescence
      signals of beta-Trp331 and beta-Trp148 as optical probes to assess formation of
      the transition state; (3) mutations of critical catalytic residues to determine
      side-chain ligands required to stabilize the transition state. Rate acceleration
      by positive catalytic site cooperativity is explained as due to mobility of alpha
      Arg376, acting as an "arginine finger" residue, which interacts with nucleotide
      specifically at the transition state step of catalysis, not with Mg-ATP- or Mg
      ADP-bound ground states. We speculate that formation and collapse of the
      transition state may engender catalytic site alpha/beta subunit-interface
      conformational movement, which is linked to gamma-subunit rotation.

PMID- 15254389
TI  - Inhibitory Mg-ADP-fluoroaluminate complexes bound to catalytic sites of F(1)
      ATPases: are they ground-state or transition-state analogs?
AB  - Schemes are proposed for coupling sequential opening and closing the three
      catalytic sites of F(1) to rotation of the gamma subunit during ATP synthesis and
      hydrolysis catalyzed by the F(o)F(1)-ATP synthase. A prominent feature of the
      proposed mechanisms is that the transition state during ATP synthesis is formed
      when a catalytic site is in the process of closing and that the transition state
      during ATP hydrolysis is formed when a catalytic site is in the process of
      opening. The unusual kinetics of formation of Mg-ADP-fluoroaluminate complexes in
      one or two catalytic sites of nucleotide-depleted MF(1) and wild-type and mutant
      alpha(3)beta(3)gamma subcomplexes of TF(1) are also reviewed. From these
      considerations, it is concluded that Mg-ADP-fluoroaluminate complexes formed at
      catalytic sites of isolated F(1)-ATPases or F(1) in membrane-bound F(o)F(1) are
      ground-state analogs.

PMID- 15254391
TI  - Murine neuronal progenitor cells are preferentially recruited to tumor
      vasculature via alpha4-integrin and SDF-1alpha-dependent mechanisms.
AB  - Recent studies have described neuronal progenitor cell recruitment to tumors in
      vivo, however, the mechanisms mediating this recruitment are not yet understood.
      When C17.2 murine neuronal progenitors stably expressing luciferase (C17.2-luc)
      were adoptively transferred into mice carrying subcutaneous Lewis lung carcinomas
      they accumulated at 1% injected dose/g of tumor tissue. C17.2-luc demonstrated
      significantly greater accumulation and transmigration on tumor-derived
      endothelium (TEC) than on normal endothelium under physiologically relevant flow
      conditions. Function blocking of alpha4-integrin reduced recruitment of C17.2-luc
      cells to normal endothelium but not to TEC, however, function blocking of SDF
      1alpha reduced overall accumulation of C17.2-luc on TEC and specifically reduced
      transendothelial migration. Together, these data suggest that recruitment of
      C17.2-luc cells to TEC is mediated via SDF-1alpha/CXCR4 activation that results
      in modification of alpha4-integrin and results in improved recruitment of C17.2
      luc cells.

PMID- 15254390
TI  - Vanadyl as a probe of the function of the F1-ATPase-Mg2+ cofactor.
AB  - The Mg2+ dependent asymmetry of the F(1)-ATPase catalytic sites leads to the
      differences in affinity for nucleotides and is an essential component of the
      binding-change mechanism. Changes in metal ligands during the catalytic cycle
      responsible for this asymmetry were characterized by vanadyl (V(IV) + O)2+, a
      functional surrogate for Mg2+. The (51)V-hyperfine parameters derived from EPR
      spectra of VO2+ bound to specific sites on F(1) provide a direct probe of the
      metal ligands. Site-directed mutations of metal ligand residues cause measurable
      changes in the (51)V-hyperfine parameters of the bound VO2+, thereby providing a
      means to identification. Initial binding of the metal-nucleotide to the low
      affinity catalytic site conformation results in metal coordination by hydroxyl
      groups from the P-loop threonine and catch-loop threonine. Upon conversion to the
      high-affinity conformation, carboxyl groups from the Walker homology B aspartate
      and MF(1)betaE197 become ligands in lieu of the hydroxyl groups.

PMID- 15254392
TI  - Induction of H2AX phosphorylation in pulmonary cells by tobacco smoke: a new
      assay for carcinogens.
AB  - DNA double strand breaks (DSBs) are potentially carcinogenic lesions. The
      induction of DSBs triggers phosphorylation of histone H2AX. Phosphorylated H2AX,
      denoted p-H2AX, may be detected immunocytochemically and the intensity of p-H2AX
      immunofluorescence (IF) reveals the frequency of DSBs. Using this assay we tested
      whether the exposure of A549 human pulmonary adenocarcinoma cells to tobacco
      smoke, and normal human bronchial epithelial cells (NHBE) to tobacco smoke
      condensate, induces DSBs. Cellular p-H2AX IF and DAPI fluorescence of individual
      cells were measured by laser scanning cytometry (LSC). Exposure of A549 cells to
      tobacco smoke and NHBE cells to smoke condensate led to H2AX phosphorylation in
      both a time and dose dependent manner. The maximal rate of H2AX phosphorylation
      was seen during the initial 4h of cell treatment. At high doses (50 microg/ml of
      smoke condensate), H2AX phosphorylation continued to increase for up to 24h. No
      differences in the level of H2AX phosphorylation were apparent between cells in
      G(1) vs S vs G(2)/M phase of the cell cycle in response to treatment with smoke
      condensate. The data provide strong evidence that exposure of A549 cells to
      tobacco smoke or NHBE cells to smoke condensate rapidly induces DSBs in these
      cells. The present assay to detect and measure DSBs induced by tobacco products
      complements other mutagenicity assays and may be applied to test potential
      carcinogens in other products.

PMID- 15254393
TI  - Histone deacetylase inhibitor enhances the anti-leukemic activity of an
      established nucleoside analogue.
AB  - Interest in histone deacetylase (HDAC) inhibitors as antineoplastic agents has
      been accelerating over the last several years and increasing number of compounds
      are in or entering clinical trials in humans. Recently, attention has been
      focused on the ability of HDAC inhibitors to induce perturbations in cell cycle
      regulatory proteins (e.g. p21CIP1), down regulation of survival signaling
      pathways (e.g. Raf/MAPkinase/ERK), and disruption of cellular redox state (e.g.
      reactive oxygen species, ROS). In April 2004 issue of Cancer Research, Maggio et
      al. report that pre-treatment of human leukemic cells with a histone deacetylase
      inhibitor, MS-275 significantly enhances the abrogative capacity of an
      established nucleoside analogue, fludarabine. The study indicates that apart from
      promoting acetylation of histones and regulation of genes involved in
      differentiation and apoptosis, MS-275 also induces multiple perturbations in
      signal transduction, survival and cell cycle regulatory pathways that increase
      the fludarabine-mediated cell death.

PMID- 15254394
TI  - Regulation of transcription and translation by hypoxia.
AB  - The maintenance of oxygen (O2) homeostasis is critical for embryonic development
      and postnatal life. In response to hypoxia, higher eukaryotes have developed
      coordinated mechanisms at both the transcriptional and translational levels to
      cope with this stress. Transcription of genes controlling glycolysis, glucose
      transport, cell survival and death, angiogenesis and erythropoiesis are activated
      (primarily by the hypoxia-inducible factor [HIF]) to facilitate cell survival and
      restore O2 homeostasis. During hypoxia, global protein synthesis is reduced to
      conserve ATP, while translation of factors like HIF-1alpha and VEGF that are
      critical for the hypoxic response is maintained by initiation via an internal
      ribosomal entry mechanism. This review addresses the regulatory effects of
      hypoxia on mRNA transcription and translation. As hypoxia is induced by tumor
      growth and affects tumor progression and metastasis, unraveling the basis of
      hypoxic control of transcription and translation will provide a better
      understanding of cancer physiology and development of anti-tumor therapies.

PMID- 15254395
TI  - The production and localization of GTP-bound ran in mitotic mammalian tissue
      culture cells.
AB  - The RanGTPase system has multiple functions in both interphase and mitosis.
      Extensive studies of Ran-driven nucleocytoplasmic transport have contributed
      significantly toward our understanding of how RanGTP is produced, hydrolyzed, and
      localized in interphase. However, there is still a lack of understanding about
      how this system operates in mitosis. Recent advances have begun to shed light on
      how RanGTP is produced and localized in mitotic mammalian cells.

PMID- 15254396
TI  - The ARTS connection: role of ARTS in apoptosis and cancer.
AB  - ARTS is an unusual septin that is localized to mitochondria in living cells and
      promotes apoptosis by antagonizing IAPs. ARTS functions as a tumor suppressor in
      Acute Lymphoblastic Leukemia (ALL) and is lost in more than 70% of leukemic
      patients. The loss of ARTS is specific as levels of H5, a closely related non
      apoptotic septin protein derived from the same gene, were unaffected. Thus, ARTS,
      a new member in the mitochondrial pro-apoptotic arsenal, provides a link between
      mitochondria, apoptosis and cancer.

PMID- 15254397
TI  - BRCA1 and transcription.
AB  - The BRCA1 tumor suppressor gene is expressed in all mammalian cells. Within these
      cells, the BRCA1 protein product interacts with several seemingly distinct
      nuclear complexes. Proteins within these complexes are potential targets for the
      E3-ubiquitin ligase activity associated with BRCA1:BARD1 complexes. Recent
      breakthroughs have centered on elucidating critical DNA repair and chromatin
      remodeling functions associated with BRCA1 activity. During both DNA replication
      and DNA repair, BRCA1 appears to serve both adaptor and enzymatic functions.
      Roles include transient physical recruitment of NBS1, gammaH2AX, FANCD2 and other
      proteins in specific repair associated complexes, and enzymatic activity as an E3
      ubiquitin ligase against a subset of these proteins. BRCA1 has also been
      implicated as a regulator of transcription. It is in this second capacity that
      progress has been much more difficult to assess. In particular, unambiguous
      adaptor and enzymatic functions have yet to be demonstrated in transcriptional
      machinery. Addressing the critical gap in our understanding of enzymatic targets
      of BRCA1 will be required for significant future progress in this field. The
      following review puts forward a model for BRCA1 interactions with the
      transcriptional complex in undamaged cells, and a potential mechanism for
      substrate switching between transcription and DNA-repair complexes following
      exposure of cells to proliferative or genotoxic stress. This model incorporates
      recent evidence that BRCA1 interacts predominantly with hyper-phosphorylated,
      enzymatically active, RNA polymerase II (RNAPII) in undamaged cells. The model
      proposes that BRCA1 binds processive RNA polymerase as part of a genome
      surveillance function, upstream of critical roles in DNA repair.

PMID- 15254398
TI  - Nucleophosmin, HDM2 and p53: players in UV damage incited nucleolar stress
      response.
AB  - p53 tumor suppressor protein acts as a critical monitor preventing survival of
      cells with irreparable genetic damage. Its levels are tightly controlled by its
      negative regulator HDM2, and are allowed to rise only during cellular stress. In
      our recent paper (Kurki, et al. Cancer Cell 2004; 5:465-75) we identify a novel
      mechanism leading to p53 stabilization following UV damage of the cells. This
      involves UV damage provoked nucleoplasmic relocalization of a nucleolar protein,
      nucleophosmin (NPM, B23) and its rapid and transient interactions with both p53
      and HDM2. We discuss here implications of recent findings that several p53
      pathway proteins interact with NPM and find that its participation in cellular
      damage responses is limited to transcriptional stress but absent in direct ds DNA
      breaks. These findings suggest divergence in the routes provoking p53 stability
      and implicate the nucleolus as a central site participating in transcriptional
      stress responses.

PMID- 15254399
TI  - The finger domain of the human deubiquitinating enzyme HAUSP is a zinc ribbon.
AB  - Human deubiquitinating enzyme HAUSP is a cysteine protease that regulates the
      levels of the tumor suppressor protein p53. By comparative sequence and
      structural analysis, we show that the previously uncharacterized finger domain
      insert to the catalytic core of HAUSP is a zinc ribbon that has lost its zinc
      binding ability.

PMID- 15254400
TI  - Genomic instability in cancer: biological and mathematical approaches.
AB  - Genomic instability occurs in a majority of cancers. It manifests itself in a
      large number genetic alterations in cancer cells, such as small scale mutations,
      losses and gains of whole chromosomes and parts of chromosomes and mitotic
      recombinations. The role of genomic instability is still unknown. It is difficult
      to study because of its heterogeneous nature. Most methods based on looking for
      defined features of genes or gene expressions, are not applicable for unstable
      populations of cells. A variety of approaches are used to study genomic
      instability. These include experimental studies of cancer cell lines and mouse
      models, analysis of large amounts of data on loss of heterozygocity, and
      mathematical modeling of the relevant processes. We describe these approaches
      here; integration of different methods can improve our understanding of genomic
      instability.

PMID- 15254401
TI  - Interference of BCR-ABL1 kinase activity with antigen receptor signaling in B
      cell precursor leukemia cells.
AB  - The chromosomal translocation t,(9;22) resulting in the fusion of the BCR and
      ABL1 genes, represents a recurrent aberration in B cell precursor leukemia cells.
      Their normal counterparts, B cell precursor cells, are positively selected for
      survival signals through the antigen receptor, whose expression requires a
      functional immunoglobulin heavy chain (IGH) gene rearrangement. Unexpectedly, B
      cell precursor leukemia cells harboring a BCR-ABL1 gene rearrangement do not
      depend on antigen receptor mediated survival signals. Genes involved in the
      signaling cascade of the antigen receptor are silenced and in most cases, the
      dominant tumor clone does not carry a functional IGH gene rearrangement. However,
      upon inhibition of the BCR-ABL1 kinase activity by STI571, only leukemia cells
      expressing an antigen receptor are able to survive. Since resistance to STI571 is
      frequent in the therapy of BCR-ABL1(+) B cell precursor leukemia, antigen
      receptor signaling may represent a mechanism through which these cells can
      temporarily evade STI571-induced apoptosis. This may open a time frame, during
      which leukemia cells acquire secondary transforming events that confer definitive
      resistance to STI571.

PMID- 15254402
TI  - Metamorphosis from bone marrow derived primitive stem cells to functional liver
      cells.
AB  - Both stem cell plasticity and cell fusion have been implicated as physiological
      responses to tissue injury. It remains the ultimate goal for the future to
      understand the regulatory control of each during regeneration. In our recent
      paper by Jang et al. we demonstrate the repair of damaged liver by bone marrow
      derived stem cells (SCs) in response to microenvironmental cues. Within 48 hrs
      after transplantation or co-culture, conversion of SCs into liver cells was
      observed. Fusion was ruled out as a major mechanism of this functional
      regeneration. Direct differentiation of SCs into liver epithelial cells may be
      clinically useful. However, if plasticity or fusion results in abnormal genetic
      changes they could be harmful. Before proceeding with therapeutic applications,
      the consequences of cellular therapy accompanying both plasticity and fusion must
      be examined in multiple animal models. Functional repair should also be
      demonstrated prior to treatment in patients.

PMID- 15254403
TI  - Induction of p53-dependent apoptosis in HCT116 tumor cells by RNA viruses and
      possible implications in virus-mediated oncolysis.
AB  - Recent findings showed that type I interferons (IFN-alpha/beta) induce the
      transcription of tumor suppressor p53 and sensitize primary mouse embryonic
      fibroblasts (MEFs) to p53-mediated apoptosis by oncolytic viruses. However, the
      ability of RNA viruses to induce a p53-mediated apoptotic response may differ
      between primary and tumor cells and may be dependent upon the virus type. We have
      investigated this hypothesis by analyzing the apoptotic effects of various
      oncolytic viruses on the human colon carcinoma HCT116 cells and their derivatives
      lacking either p53 or bax gene. We show that HCT116 cells are resistant to the
      apoptotic effects of vesicular stomatitis virus, reovirus or poliovirus but
      activate the p53/Bax apoptotic pathway after infection with Sendai virus. These
      data substantiate the role of p53 in virus-mediated apoptosis and show that,
      unlike primary cells, tumor cells may be more selective in the activation of p53
      pathway in response to the infection with specific types of viruses.

PMID- 15254404
TI  - A Role for the RSC chromatin remodeler in regulating cohesion of sister chromatid
      arms.
AB  - The precise segregation of chromosomes is critical for the proliferation and
      development of living organisms. Defects in this process can result in
      tumorigenesis and hereditary diseases. The four-subunit cohesin complex plays an
      essential role in chromosome segregation and genome integrity. Recently, we
      reported that the association of cohesin with centromeres and chromosome arms is
      differentially regulated by the ATP-dependent RSC chromatin-remodeling complex.
      Here, we propose two models to explain why the cell should have evolved special
      mechanisms for centromeric and sister arm cohesion and why RSC differentially
      regulates these processes.

PMID- 15254405
TI  - Improving cancer therapy through p53 management.
AB  - The tumor suppressor p53 normally acts to appropriately coordinate cellular
      responses to stress stimuli. When p53 activity is disabled, the onset of
      malignancy is a potential consequence. Engendering wild type p53 activities in
      cells that lack these functions is an approach that is currently being explored
      for cancer therapy. Eliciting elevated levels of active p53, imparting p53
      activities through gene therapy, compelling mutant p53 to perform normal
      functions, manipulating p53 regulators, and activating p53 effectors are all
      approaches that are currently being developed. In this review we will provide a
      synopsis of the most promising 'p53-based' strategies for fighting cancer, both
      those under clinical trial and recent innovative concepts.

PMID- 15254406
TI  - Complete and limited proteolysis in cell cycle progression.
AB  - An important mechanism of regulation that controls progression through the cell
      cycle involves the timely degradation of specific regulatory proteins. In
      parallel to the main degradative pathways, it appears that the function of
      certain proteins may also be modulated by a process called limited proteolysis.
      We have recently shown that the CDP/Cux transcription factor is proteolytically
      processed at the G(1)/S transition by the cathepsin L protease. Two aspects of
      these findings are discussed in the context of the cell cycle. Firstly, together
      with the cohesin subunit Scc1 and the HCF-1 factor, CDP/Cux represents a third
      example whereby the process of "limited proteolysis" plays a role in the control
      of cell cycle progression. Secondly, our findings provides compelling evidence
      that the cathepsin L protease, which was believed to be obligatorily targeted
      through the endoplasmic reticulum to the lysosomes or the extra-cellular milieu,
      could also be present in the nucleus and modulate the function of transcription
      factors.

PMID- 15254407
TI  - Vascular endothelial growth factor augments human herpesvirus-8 (HHV-8/KSHV)
      infection.
AB  - Human herpesvirus-8 (HHV-8/KSHV) is etiologically associated with Kaposi's
      sarcoma (KS) and other tumors. The Raf oncoprotein enhances HHV-8 infection of
      target cells. In addition, we have previously demonstrated that Raf induces
      vascular endothelial growth factor (VEGF) expression. VEGF is a growth factor
      that has autocrine growth activity and has been implicated in the formation of
      the spindle shape cell morphology characteristic of Kaposi's sarcoma (KS). The
      aim of this study was to test the hypothesis that VEGF enhances infection of HHV
      8. Herein, we demonstrate that the soluble VEGF enhanced green florescence
      protein encoding (GFP)-HHV-8 (rKSHV.152) infection of human foreskin fibroblasts
      (HFF) and not of 293 cells. We found this to be in part, due to the fact that HFF
      inherently produces significantly lower concentrations of VEGF when compared to
      293 cells. Treating 293 cells (but not HFF) with a VEGF receptor (VEGFR)
      inhibitor significantly lowered infection. Furthermore, transfecting 293 cells
      with VEGF specific si-RNA did not alter the binding of HHV-8 to cells; but
      significantly lowered VEGF expression and thus GFP-HHV-8 infection.
      Interestingly, lowering VEGF expression in 293 cells wtih VEGF specific si-RNA
      did not completely inhibit GFP-HHV-8 infection. We conclude that VEGF is not a
      requirement for HHV-8 infection; but VEGF plays a major role in augmenting
      infection at a post binding stage of entry. These findings suggest that targeting
      VEGF/VEGFR may prove efficacious in controlling HHV-8 associated pathogenesis.

PMID- 15254408
TI  - Activating FOXO3a, NF-kappaB and p53 by targeting IKKs: an effective multi
      faceted targeting of the tumor-cell phenotype?
AB  - Tumor cells frequently recruit the PI3K/Akt pathway in order to evade cell death,
      terminal differentiation and replicative inhibition. A wealth of targets for the
      PI3K/Akt pathway involved in these processes has been described. Among others,
      targets for the Akt-kinase include certain members of the Forkhead Box Class O
      (FOXO) transcription factors, involved in DNA damage repair, apoptosis, cell
      cycle progression and arrest. Akt regulates the sub-cellular localization of
      FOXO3a by phosphorylation thereby preventing the protein to translocate to the
      nucleus and regulate transcription. Constitutive Akt-activation is frequently
      correlated with cytoplasmatic FOXO3a in breast tumors and this is associated with
      decreased patient survival. In a recent paper (Hu MC, et al. Cell 2004; 117:225
      237) FOXO3a was found in the cytoplasm in the absence of activated Akt. Instead,
      IKKbeta was shown to interact with and phosphorylate FOXO3a. The recent findings
      suggest that the IKKs might serve as a potential drug target in anti-cancer
      therapy since multiple signal transduction pathways inhibiting proliferation and
      facilitating cell death could be activated.

PMID- 15254409
TI  - Cyclin mRNA stability does not vary during the cell cycle.
AB  - The cyclins are tightly regulated elements governing eukaryotic cell cycle
      progression by means of sequential activation-inactivation of cyclin-dependent
      kinases. In one manifestation of this regulation, the mRNA levels of several
      cyclin genes oscillate during the cycle in mammalian cells. Such cycle-dependent
      fluctuations in transcript levels could result from changes not only in rates of
      transcription, but also in mRNA stability. Here we used a new, minimally
      disturbing method for producing multi-cycle synchronous growth of human MOLT-4
      cells, in combination with quantitative real-time RT-PCR, to compare cell cycle
      dependent transcript levels and half-lives of cyclin A2, B1, D3, E and PCNA
      mRNAs. While all mRNA levels except cyclin D3 varied in the cycle, there were no
      apparent variations in message half-lives. This differs from several previous
      reports of dramatic fluctuations in the stabilities of cyclin mRNAs, and infers
      that fluctuations in cyclin mRNA transcript levels during the MOLT-4 cell cycle
      are not due to variations in half-lives. The discrepancy in mRNA stability
      determinations could be due to differences in cell types or synchronization
      methods, but our findings may be representative of mRNA processing in the cycle
      of cells in unstressed steady-state growth.

PMID- 15254410
TI  - 2-deoxy-D-glucose enhances the cytotoxicity of topoisomerase inhibitors in human
      tumor cell lines.
AB  - Resistance of tumors due to restricted drug accumulation and reversal of DNA
      lesions in tumor cells as well as normal tissue toxicity limit the efficacy of
      topoisomerase inhibition based anticancer drugs. It has been proposed that
      selective inhibition of energy dependent repair processes and enhanced retention
      of drug in cancer cells can significantly improve the therapeutic efficacy. The
      purpose of these studies was to verify this proposition by investigating the
      effects of 2-deoxy-D-glucose (2-DG) an inhibitor of the glycolytic ATP production
      on the cytotoxicity of certain topoisomerase inhibitors in human tumor cell
      lines. Human glioma (BMG-1 and U-87) and squamous carcinoma (4197 and 4451) cell
      lines were investigated with topo-poisons like etoposide (topo II inhibitor),
      camptothecin (topo I inhibitor) and hoechst-33342 (topo I and II inhibitor). DNA
      damage induction (halo assay), cell survival (macro colony assay), cytogenetic
      damage (micronuclei) and apoptosis (morphological analysis) were investigated.
      Presence of 2-DG for 2 h following exposure to the topoisomerase inhibitors
      enhanced the cell death (macro colony assay) in a concentration dependent manner
      and a 2-3-fold increase was observed at 5 mM (equimolar with glucose). Halo assay
      revealed that 2-DG inhibited the reversal of cleavable complex leading to the
      accumulation of DNA strand breaks. Under these conditions 2-DG enhanced the drug
      induced micronuclei formation by nearly 2 folds with etoposide and hoechst-33342
      and a 4-fold increase in delayed apoptosis was observed in case of etoposide.
      These results clearly demonstrate that presence of 2-DG for a few hours following
      exposure to topo-inhibitors enhances the cytotoxicity, primarily by increasing
      the cytogenetic damage.

PMID- 15254411
TI  - Aqueous extract of Urtica dioica makes significant inhibition on adenosine
      deaminase activity in prostate tissue from patients with prostate cancer.
AB  - AIM: Investigation of possible effects of aqueous extract of Urtica dioica leaves
      on adenosine deaminase activity in prostate tissue from patients with prostate
      cancer. METHODS: Ten prostate tissues from patients with pathologically proven
      localized prostate cancer (Gleason scores 4 to 7) were used in the study. In the
      tissues, ADA activities with and without preincubation with different amounts of
      Urtica dioica extracts were performed. RESULTS: Aqueous extract of Urtica dioica
      results in significant inhibition on adenosine deaminase (ADA) activity of
      prostate tissue. CONCLUSION: ADA inhibition by Urtica dioica extract might be one
      of the mechanisms in the observed beneficial effect of Urtica dioica in prostate
      cancer.

PMID- 15254412
TI  - Imatinib: paradigm or anomaly?
AB  - The introduction of imatinib (Gleevec, Glivec, formerly STI571), an agent
      targeting the causative molecular event in chronic myeloid leukemia (CML) has
      been heralded as a major advance in the treatment of cancer. Certainly, the
      clinical trials with imatinib have validated the concept that a precise
      understanding of the pathogenesis of a cancer can lead to more effective and less
      toxic therapies. Despite the success of imatinib, there remains much skepticism
      that this paradigm will be applicable to more complicated solid tumors. Whether
      this skepticism is appropriately deserved will be discussed.

PMID- 15254413
TI  - Unraveling genes and pathways influenced by H-prune PDE overexpression: a model
      to study cellular motility.
AB  - H-prune, a new cyclic nucleotide phosphodiesterase, binds to nm23-H1, a
      metastasis suppressor protein. The overexpression of h-prune in the MDA-MB-435
      breast carcinoma cell line causes a substantial decrease of cAMP, and an increase
      in cellular motility. This latest effect is correlated both to the h-prune
      phosphodiesterase activity and to the interaction between h-prune and nm23-H1
      proteins. Understanding the molecular changes in tumor cells with an increased
      level of expression of h-prune might shed light on motility processes, which are
      the driving forces of the cells to move away from the primary tumor and to become
      metastatic. This report overview genes and pathways influenced by h-prune
      overexpression in a conventional breast cancer cellular model.

PMID- 15254414
TI  - Genetic epidemiology of BRCA1.
AB  - Since the identification of the BRCA1 gene 10 years ago much has been learned
      about the role of the BRCA1 protein in cancer development. In particular, genetic
      and epidemiological approaches have informed about the spectrum of mutations that
      occur in the gene and the prevalence, penetrance, and phenotype associated with
      these mutations in various populations. Furthermore, advances have been made in
      understanding the environmental and genetic modifiers of cancer risk associated
      with BRCA1 mutations. In this review the current knowledge of the genetic
      epidemiology of BRCA1 is presented and the issues that still need to be addressed
      in this field are outlined.

PMID- 15254415
TI  - Dynamics in the p53-Mdm2 ubiquitination pathway.
AB  - The tumor suppressor p53 is highly regulated under various states of cellular
      stress. p53 stability is predominantly regulated through the ubiquitin
      proteasomal pathway by the E3 ligase Mdm2. p53 ubiquitination is a dynamic
      process with Mdm2 capable of catalyzing both mono- and polyubiquitination.
      Additionally, deubiquitination is an important step occurring in p53 and Mdm2
      stabilities. Factors such as HAUSP, p14(ARF), and MdmX play important regulatory
      roles in p53 ubiquitination/deubiquitination and their interplay with Mdm2 and
      p53 compound layers of complexity for regulating this important pathway.

PMID- 15254416
TI  - p73 and p63: why do we still need them?
AB  - When p73 and p63 were initially described as homologues of the tumor suppressor
      p53, the three family members seemed almost exchangeable, raising the question
      why all three were retained during evolution. It later turned out that the
      corresponding genes, TP63 and TP73, appear phylogenetically older than TP53, and
      that their targeted deletion causes severe developmental defects, in contrast to
      a deletion of TP53. Hence, p63 and p73 are responsible for biological effects
      that cannot be elicited by p53 alone. Here, we provide an overview of properties
      ascribed to p63 and p73 that distinguish them from p53. Differences occur at the
      following levels: (i) protein structure, especially with regard to the
      aminoterminal transactivation domains and the carboxyterminal portions unique to
      p63 and p73; (ii) regulation, affecting mRNA levels, posttranslational
      modifications and interaction with other cellular proteins; (iii) activities,
      resulting in the regulation of gene expression, the programming of development,
      and the emergence of tumors. We speculate that, during the course of evolution,
      p63 and p73 have first pursued a broader range of activities, whereas p53 later
      specialized on genome maintenance.

PMID- 15254417
TI  - Paclitaxel induces primary and postmitotic G1 arrest in human arterial smooth
      muscle cells.
AB  - Paclitaxel (PTX), a microtubule-active drug, causes mitotic arrest leading to
      apoptosis in certain tumor cell lines. Here we investigated the effects of PTX on
      human arterial smooth muscle cell (SMC) cells. In SMC, PTX caused both (a)
      primary arrest in G(1) and (b) post-mitotic arrest in G(1). Post-mitotic cells
      were multinucleated (MN) with either 2C (near-diploid) or 4C (tetraploid) DNA
      content. At PTX concentrations above 12 ng/ml, MN cells had 4C DNA content
      consistent with the lack of cytokinesis during abortive mitosis. Treatment with 6
      12 ng/ml PTX yielded MN cells with 2C DNA content. Finally, 1-6 ng/ml of PTX, the
      lowest concentrations that affected cell proliferation, caused G(1) arrest
      without multinucleation. It is important that PTX did not cause apoptosis in SMC.
      The absence of apoptosis could be explained by mitotic exit and G(1) arrest as
      well as by low constitutive levels of caspase expression and by p53 and p21
      induction. Thus, following transient mitotic arrest, SMC exit mitosis to form MN
      cells. These post-mitotic cells were subsequently arrested in G(1) but maintained
      normal elongated morphology and were viable for at least 21 days. We conclude
      that in SMC PTX causes post-mitotic cell cycle arrest rather than cell death.

PMID- 15254418
TI  - Analysis of FDA approved anticancer drugs reveals the future of cancer therapy.
AB  - This review discusses 26 new anticancer drugs approved by the FDA in the past
      decade. Based on their targets, these anticancer agents can be divided into three
      groups. First group contains cancer-selective or semi-selective drugs that are
      effective in rare kinase- addictive cancers. For other malignancies, semi
      selective drugs have to be judiciously combined with nonselective agents. The
      second group includes analogs of classic cytotoxic agents such as DNA alkylating
      agents, nucleoside analogs, and anti-microtubule agents. As expected, they have a
      marginal advantage over the existing cytotoxic drugs, nevertheless are more
      effective (in common cancers) than semi-selective agents. The third is a diverse
      group of tissue-selective agents that essentially attack the normal tissues of
      tumor origin and thus exploit the tissue-specific similarities between normal and
      cancer cells. Our analysis predicts that monotherapy with semi-selective agents
      will be limited to rare cancers. In most cancers, however, two anticancer
      strategies may be most fruitful: (a) combinations of cytotoxic drugs with semi
      selective agents aimed at matching targets and (b) tissue-selective therapy aimed
      at normal and tumor cells of the same tissues.

PMID- 15254419
TI  - The PIK3CA gene is mutated with high frequency in human breast cancers.
AB  - The phosphatidylinositol 3-kinases (PI3Ks) are known regulators of cellular
      growth and proliferation. It has recently been reported that somatic mutations
      within the PI3K subunit p110alpha (PIK3CA) are present in human colorectal and
      other cancers. Here we show that thirteen of fifty-three breast cancers (25%)
      contain somatic mutations in PIK3CA, with the majority of mutations located in
      the kinase domain. These results demonstrate that PIK3CA is the most mutated
      oncogene in breast cancer and support a role for PIK3CA in epithelial
      carcinogenesis.

PMID- 15254420
TI  - Comparison of genetic changes between interphase and metaphase nuclei in
      monitoring CML and APL treatment using DC-FISH technique.
AB  - In leukemias, the monitoring techniques on the response after the treatment have
      clinical importance for evaluating new therapeutic approaches and identifying the
      risk of relapse. In this study, genetic changes before and after chemotherapy in
      interphase and metaphase nuclei of bone morrow of adults with provisional
      diagnosis of leukemia were compared to understand the molecular characterization
      and pathogenesis of the leukemia for the classification of diagnosis and
      prognosis. We examined bone morrow cells of 47 chronic myeloid leukemia (CML)
      cases (29 of 47 at the time of diagnosis, 31 of 47 after chemotherapy) with the
      bcr/abl translocation probes and of 10 acute promyelocytic leukemia (APL) cases
      (7 of 10 at the time of diagnosis, 4 of 10 after chemotherapy) with the
      PML/RARalpha translocation probes by using dual color-flourescence in situ
      hybridization (DC-FISH). For each case, 400 interphase nuclei and 11 to 25
      metaphases nuclei were analysed. The ratios of translocations before and after
      chemotherapy were compared between interphase and metaphase nuclei. After
      chemotherapy, though, translocations were detected in interphase nuclei of 29 of
      the 31 CML and 4 of the 4 APL cases, these translocations were determined in
      metaphase nuclei of only 14 of the 31 CML and 1 of the 4 APL cases with very low
      ratios (p < 0.01). The results showed that the rates of translocation positive
      interphase nuclei were higher than the rates of translocation positive metaphase
      nuclei (p < 0.01) after chemotherapy, so there may be some factors effecting
      proliferative activity of metaphase formation in leukemias.

PMID- 15254421
TI  - Precise dosage of an endogenous mutagen in the immune system.
AB  - Four decades ago, it was hypothesized that lymphocytes mutate the immunoglobulin
      loci at a rate much greater than the spontaneous rate. Over time this Ig somatic
      hypermutation became the prime example of in vivo, site-directed mutagenesis. But
      recent studies have demonstrated that this is not necessarily the case, and that
      hypermutation occurs not only at the Ig locus but also at various locations
      throughout the genome. Here, we propose that hypermutation can be genome-wide
      with minimal injury, if a sufficient mutation rate is coupled with strong clonal
      selection.

PMID- 15254422
TI  - Control of erythropoiesis by erythropoietin and stem cell factor: a novel role
      for Bruton's tyrosine kinase.
AB  - Erythropoietin (Epo) and stem cell factor (SCF) are essential factors in the
      control of survival, expansion and differentiation of erythroid progenitors. Upon
      activation, their receptors, the EpoR and c-Kit, initiate multiple signalling
      pathways that control many cellular processes. To control erythropoiesis, the
      strength, duration and specificity of signalling must be tightly controlled.
      Negative feed-back regulation is extensively studied, but positive feed-forward
      control is relatively little studied. The cytoplasmic tyrosine kinase Bruton's
      tyrosine kinase (Btk) was found to be phosphorylated by Jak2 in response to Epo
      and appeared to be required for fast and efficient phosphorylation of Epo-induced
      targets including the EpoR itself and downstream targets such as PLCgamma and
      Stat5. Erythroid progenitors deficient in Btk fail to undergo renewal divisions
      and differentiate instead at low, physiologic concentrations of Epo and SCF. In
      addition, Btk is phosphorylated by SCF, which causes association of Btk with
      TRAIL-receptor1. In absence of Btk, erythroid progenitors are hypersensitive to
      TRAIL. Thus, Btk modulates signalling in erythroid progenitors to enhance
      expansion of erythroid progenitors. The complexity of signalling by the EpoR/c
      Kit signalosome and its control by Btk is discussed with respect to normal and
      aberrant erythropoiesis.

PMID- 15254423
TI  - EGFR autocrine signaling in a compliant interstitial space: mechanotransduction
      from the outside in.
AB  - Cells transduce mechanical forces into biochemical signals; traditionally these
      processes are thought to occur through direct effects on the cell membrane, the
      cytoskeleton, or specific transmembrane proteins. In multicellular tissues
      mechanical forces alter intercellular spacing through redistribution of
      interstitial fluid. Recent morphological and biochemical observations, bolstered
      by analytical modeling, support a new paradigm for mechanotransduction arising
      from constitutive growth factor shedding into a dynamically regulated
      interstitial volume.

PMID- 15254424
TI  - Understanding germ-line mutations in BRCA1.
AB  - Germ-line mutations in BRCA1 account for the majority of familial breast and
      ovarian cancer cases and development of cancer in individuals who carry such
      mutations requires somatic inactivation of the normal allele. BRCA1 is highly
      polymorphic with more than 1,200 distinct documented variants. Approximately 70%
      of reported variants lead to absence of full-length BRCA1 protein, through loss
      of expression or protein truncation, and are suspected to predispose to cancer.
      These include regulatory mutations, splice site alterations, large
      rearrangements, large and small deletions or insertions, and nonsense mutations.
      However, characterizing the remaining missense alterations as either deleterious
      (cancer-associated mutations) or neutral variants is more complex, as the
      functional significance of the respective amino acid substitution is not
      straightforward to evaluate. In addition, many missense variants have been
      identified only once in defined ethnic groups and represent alleles with very low
      frequency. Most often, little information is available about segregation of the
      variant with disease in families, and assessment of disease risk for low
      frequency alleles through association studies is problematic, requiring a large
      number of samples stratified and matched by ethnicity. The fact that a
      significant proportion of BRCA1 variants remain unclassified represents a gap in
      risk assessment, such that individuals undergoing genetic testing will receive
      noninformative test results. An approach for assessing the potential clinical
      significance of missense variants is to combine available genetic data with
      functional and structural studies. Here we review the available information on
      BRCA1 variants and explore ways in which we can analyze unclassified variants.

PMID- 15254425
TI  - Myc tagging along the TRAIL to death receptor 5.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL; also known as
      Apo2L) is an apoptotic cytokine that is being developed as a novel anticancer
      agent. TRAIL mediates its effect via death receptors 4 (DR4) and DR5 and appears
      to selectively induce apoptosis in cancer cells. The molecular basis of why
      normal cells seem to better tolerate this novel cytokine remains unknown.
      Recently, it has been reported that Myc oncoprotein by upregulating DR5 appears
      to augment cellular susceptibility to TRAIL and to DR5 agonistic antibodies.
      Several previous studies have already established that various clinically
      relevant agents by upregulating DR5 sensitize cells to TRAIL. However, the
      finding that DR5 is upregulated by an oncoprotein that is overexpressed in
      several tumor types is noteworthy and may spark future investigations aiming to
      explore the Myc and DR5 expression status of primary tumors and their ultimate
      vulnerability to DR5-targeted therapeutics.

PMID- 15254426
TI  - Epigenetic regulation of MDR1 gene in breast cancer: CpG methylation status
      dominates the stable maintenance of a silent gene.

PMID- 15254427
TI  - p53-Dependent activation of a molecular beacon in tumor cells following exposure
      to doxorubicin chemotherapy.
AB  - In an effort to begin developing a non-invasive strategy for in-vivo detection of
      the cellular DNA damage response, we engineered a molecular beacon to detect
      expression of p21(WAF1/CIP1), a gene whose transcription is directly activated by
      the p53 tumor suppressor protein. Introduction of a phosphorothioate-modified p21
      beacon by transfection in human tumor cells led to a slight background signal
      that increased in a dose dependent manner between 50 and 400 nM beacon. Strong
      nuclear signal was observed following treatment of wild-type p53-expressing human
      H460 lung cancer cells for 8 hours with the chemotherapeutic agent doxorubicin
      (adriamycin). Similar induction was observed in wild-type p53-expressing HCT116
      cells. Interestingly, following doxorubicin exposure, there was activation of the
      p21-beacon in p21-null HCT116 cells, which was not observed in p53-null HCT116,
      or mutant p53-expressing DLD1 cells that are either wild-type or p21-null.
      Increased signal from the phosphorothioate-modified p21-beacon in doxorubicin
      treated cells likely resulted from sequence-specific hybridization as well as
      sequence-independent cleavage that may occur due to p53-dependent activation of
      endonucleases during apoptosis. We conclude that activation of p53 by
      chemotherapy leads to a strong signal from a p21-beacon that may be useful in
      further testing both in vitro and in vivo. Strategies need to be developed to
      optimize the gene or damage specificity as well as the sensitivity to therapeutic
      response of this non-invasive imaging approach.

PMID- 15254428
TI  - Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary
      and metastatic head and neck cancer and its modulation by celecoxib.
AB  - Eicosanoid metabolism through cyclooxygenases (COXs) and lipoxygenases (LOXs)
      generates various lipids that play a role in squamous cell carcinogenesis. We
      used pairs of head and neck squamous cell carcinoma (HNSCC) cell lines derived
      from primary and metastatic tumors of the same patient to analyze eicosanoid
      metabolites by ESI-LC/MS/MS and COX/LOX expression by western immunoblotting. The
      effects of celecoxib on eicosanoid synthesis and HNSCC cell growth were examined.
      Prostaglandin E2 (PGE2) was the major metabolite in three of six cell lines. COX
      2 was detected in three cell lines, which produced PGE2 (two from metastases). We
      found low expression of COX-1 at similar intensities for each pair of cell lines.
      5-LOX was detected in all cells. Some expressed 12-LOX, 15-LOX-1, and 15-LOX-2,
      but there was no correlation between enzyme expression and endogenous product
      content. Exogenous arachidonic acid did not change the profile of eicosanoid
      biosynthesis. Low doses of celecoxib inhibited formation of PGE2 in UMSCC-14A
      cells by 84% as early as 6 hours. In contrast, 5-HETE, 12-HETE, and 15-HETE
      levels were increased by approximately 40-, 5- and 3-fold, respectively, with a
      decline to baseline levels within 24 hours. High dose celecoxib increased the 12
      HETE level 2.3-fold after 3 days of incubation. Celecoxib inhibited growth of all
      HNSCC cell lines in a concentration-dependent manner regardless of their COX
      expression (IC50 values after 3 days; 33 to 62 microM). Our findings provide new
      informations about individual eicosanoids produced by HNSCC cells and their
      differential regulation by the selective COX-2 inhibitor celecoxib.

PMID- 15254429
TI  - Medulloblastoma and retinoblastoma: oncology recapitulates ontogeny.
AB  - One major factor hindering progress of pediatric cancers of the nervous system
      has been the lack of satisfactory model systems for testing novel therapies. A
      mouse strain, mutant for the Rb1 gene was generated 12 years ago in the hope of
      producing a model in which to study retinoblastoma. Surprisingly, the Rb(+/-)
      mice never developed retinoblastoma. Now, Zhang, Schweers and Dyer produce triply
      deficient Rb, p107 and p53 mutant retinal progenitor cells. All such mice develop
      intraocular retinoblastoma with invasion of the tumor into the anterior chamber
      of the eye. This dramatic finding represents the first description of a heritable
      mouse model of retinoblastoma, which has eluded investigators for the last 12
      years. Such models provide an unprecedented opportunity to advance knowledge of
      tumorigenesis and to develop non-toxic intervention strategies which eradicate
      disease.

PMID- 15254430
TI  - Chromosomal translocations and non-B DNA structures in the human genome.
AB  - The mechanisms of chromosomal translocations in mammalian cells have been largely
      undefined. Recent progress on the most common translocation in human cancer,
      t(14;18), highlights interesting issues in DNA structure and in the enzymes
      involved in the cutting and joining phases of the process.

PMID- 15254431
TI  - Mutations in the EGFR: the importance of genotyping.
AB  - Gefitinib reached the clinic with anticipation, but initial clinical trials were
      disappointing with only a small number of patients showing response to treatment.
      In two recent articles published simultaneously, Lynch et al., and Paez et al.
      help to explain those initial clinical findings. Both groups report that somatic
      mutations found within the coding region of the EGFR may predict the sensitivity
      to gefitinib treatment.

PMID- 15254432
TI  - MAD2 dependent mitotic checkpoint defects in tumorigenesis and tumor cell death:
      a double edged sword.
AB  - The failure of cell cycle regulatory checkpoints is a common event in human
      cancer. Defects at the G(1)-S transition have been widely characterized, but only
      more recently has aberrant checkpoint signaling during mitotic progression been
      identified as playing a role in cancer. The metaphase to anaphase transition is
      regulated by multiple proteins that together comprise the mitotic checkpoint.
      Previously it has been shown that loss of one copy of MAD2, a mitotic checkpoint
      gene, results in aneuploidy and tumorigenesis arising from chromosome
      missegregation. More recently and quite surprisingly, MAD2 has been demonstrated
      to be an essential gene even in tumor cells such that near complete elimination
      of this protein from cancer cells results in p53 independent cell death. This is
      the first identification of a haploinsufficient tumor suppressor gene that is
      also required for tumor cell survival, and suggests that targeting this
      checkpoint in cancer might be a viable therapeutic strategy.

PMID- 15254433
TI  - Mdmx and Mdm2: brothers in arms?
AB  - The p53 tumor suppressor pathway is inactivated in most if not all human tumors.
      In about 50% of the cases this is accomplished directly by gene mutations. The
      tumors that retain wild type p53 frequently show defects either in effector
      target genes, or in the expression of p53 regulatory proteins. The Mdm2 protein
      is generally considered THE master regulator of the p53 tumor suppressor
      activity. Recently, however, the Mdm2-related protein Mdmx is taking the stage in
      the p53-Mdm2-Mdmx play. We summarize here observations unambiguously assigning a
      critical role for the Mdmx protein in the regulation of p53 function during
      development and tumor formation.

PMID- 15254434
TI  - KeePin' the p53 family in good shape.
AB  - The tumor suppressor p53 and the prolyl isomerase Pin1 are both highly connected
      proteins, lying at the crossroads between many signaling pathways that control
      cell proliferation and transformation. By catalyzing conformational changes in a
      large number of phosphorylated proteins, Pin1 has been implicated in the
      regulation of major cellular events, such as cell cycle progression,
      transcription, proliferation and differentiation. Recently, a role for Pin1 has
      emerged also in the DNA damage response, through modulation of p53 functions upon
      genotoxic stress. A further level of control has now been unveiled by showing
      that also the p53 sibling p73 requires Pin1 for its apoptotic activity.

PMID- 15254435
TI  - An update on management of persons with human immunodeficiency virus and acquired
      immunodeficiency syndrome: introduction to symposium.

PMID- 15254436
TI  - Antiretroviral therapy in drug-naive patients infected with human
      immunodeficiency virus.
AB  - A vast amount of knowledge has accumulated since the discovery of the
      immunodeficiency diseases caused by human immunodeficiency virus-1 (HIV-1) in the
      early 1980s. An expert panel of HIV researchers and clinicians produced the first
      set of treatment guidelines in 1997. Since then, these guidelines have been
      updated based on available clinical information and supplemented by expert
      opinion when scientific data were incomplete. The latest version of the HIV
      treatment guidelines are summarized here, with attention focused on the rationale
      for treatment of asymptomatic as well as symptomatic individuals, including when
      and what to start as a first regimen of highly active antiretroviral therapy
      (HAART). Components of initial and follow-up evaluations are detailed, with
      attention given to available HIV viral load tests and their use. Because
      adherence to HAART is critical to immune recovery and stabilization, data on
      predictors of both good and poor medication compliance, as well as strategies to
      maximize medication adherence are presented. Lastly, recommendations for the use
      of HIV genotypic and phenotypic resistance testing in antiretroviral naive
      patients are presented.

PMID- 15254437
TI  - The antiretroviral-experienced patient.
AB  - There are many considerations for stopping and changing antiretroviral (ARV)
      therapy in the ARV-experienced individual. Given the potential for possible long
      term toxicities and the shift to initiating ARV therapy later, it may be
      reasonable to stop ARV therapy among asymptomatic patients with high CD4 cell
      counts and low viral loads and carefully monitor them. Ongoing studies are
      currently evaluating this strategy. Treatment regimen failure may be due to
      problems with tolerability, adherence, pharmacokinetic issues, or emergence of
      resistance. Clinicians can utilize two types of resistance testing-genotype and
      phenotype assays. Generally, continuation of an optimized regimen in the patient
      with a multidrug resistant (MDR) virus is the best strategy. Structured treatment
      interruption among patients with an MDR virus is not recommended. New drugs,
      either recently licensed, such as enfuvirtide, or under investigation, may offer
      hope to patients with an MDR virus.

PMID- 15254438
TI  - Women and human immunodeficiency virus: unique management issues.
AB  - Women currently account for an increasing proportion of the US population
      infected with human immunodeficiency virus (HIV). Although women suffer from
      similar HIV-related complications as men, they also can have unique gynecologic
      manifestations, such as cervical dysplasia or severe pelvic inflammatory disease.
      Other gender-specific management issues include contraception and pregnancy.
      Fortunately, today the perinatal HIV transmission rate can be lowered to less
      than 2% with appropriate management. More couples, including those discordant for
      HIV infection, are opting to pursue conception. Providers caring for HIV-infected
      women should be knowledgeable about reproductive choices, including the full
      array of available options. Strategies shown to improve access of health care to
      HIV-infected women include integrating gynecologic services with primary care,
      daily availability of medical services, provision of transportation, and
      provision of on-site childcare.

PMID- 15254439
TI  - Management of the coinfected patient: human immunodeficiency virus/hepatitis B
      and human immunodeficiency virus/hepatitis C.
AB  - Deaths from liver disease have increased in persons infected with human
      immunodeficiency virus (HIV) because of coinfection with chronic hepatitis B and
      C; consequently, all HIV-infected patients should be screened for hepatitis B and
      C, and all those susceptible should be vaccinated for hepatitis B. Hepatitis A
      vaccination is indicated for susceptible coinfected patients. It is also
      important to stress other means of preventing the transmission of hepatitis, such
      as safe sex and avoidance of blood exposures. Three oral agents, lamivudine,
      adefovir, and tenofovir, are active against hepatitis B infection. The need for
      highly active antiretroviral therapy and hepatitis B therapy should be addressed
      in a coordinated fashion, since two of these agents are active against both HIV
      and hepatitis B virus. Oral combination therapy for hepatitis B infection looks
      promising but needs further study. Combination therapy for chronic hepatitis C
      with pegylated interferon plus ribavirin is the most effective available therapy
      and the current standard of care. Prior to therapy, patients should be evaluated
      for contraindications to therapy. During treatment, they should be closely
      monitored for adverse events.

PMID- 15254440
TI  - Integration of palliative care into primary care for human immunodeficiency virus
      infected patients.
AB  - Palliative care for patients infected with human immunodeficiency virus (HIV)
      includes components of pain and symptom management, advance care planning,
      prioritization of life goals, and the support of individuals and families
      throughout the entire continuum of the disease. There are numerous social
      stressors such as stigma, infected family members and caregivers, loss of housing
      and independent living, and the increasing influence of substance use in all
      communities. Because many barriers prevent those with advanced disease from
      getting comprehensive pain and symptom management as well as option planning, it
      is important for all HIV care providers to improve their knowledge, sensitivity,
      and competence regarding this aspect of care. This article provides an overview
      of critical issues in palliative care and information on how best to improve HIV
      primary care.

PMID- 15254441
TI  - Metabolic complications associated with the use of highly active antiretroviral
      therapy in HIV-1-infected adults.
AB  - The availability of highly active antiretroviral therapy (HAART) has resulted in
      dramatic declines in morbidity and mortality in patients infected with human
      immunodeficiency virus-1 (HIV-1). However, the success of HAART has been tempered
      by the recognition of adverse metabolic effects clearly associated with its use.
      These "metabolic complications" include dyslipidemia, changes in body fat
      distribution, insulin resistance and glucose intolerance, metabolic bone disease,
      and lactic acidosis. Guidelines to assist clinicians in the management of these
      complications have been put forth by various organizations, including the
      International AIDS Society, the HIV Medicine Association of the Infectious
      Disease Society of America, and the Adult AIDS Clinical Trials Group.

PMID- 15254442
TI  - Human papillomavirus infection and disease in HIV-infected individuals.
AB  - The possibility of increases in both oral and anogenital pathologic conditions
      due to human papillomavirus (HPV) in patients infected with the human
      immunodeficiency virus (HIV) is of concern and is the focus of numerous current
      research studies. HIV-infected women are at higher risk for cervical HPV
      detection, for infection with high-oncogenic-risk types of HPV, for persistent
      HPV infection, for cervical cytologic abnormalities, and for cervical
      intraepithelial neoplasms. HIV-infected men are at increased risk for anal HPV
      infection, for anal infection with high oncogenic-risk types of HPV, for
      persistent anal HPV infection, and for anal intraepithelial defects. Recent
      studies have shown an increased risk of oral warts in HIV-infected individuals
      despite treatment with highly active antiretroviral therapy (HAART). Oral HPV
      infection rates have not declined since the initiation of HAART, and evidence
      suggests that the rates may have actually increased in white HIV-infected males.

PMID- 15254443
TI  - Prophylaxis against opportunistic infections in persons infected with human
      immunodeficiency virus.
AB  - This article outlines the current official recommendations for the prevention of
      opportunistic disease in adults and adolescents infected with human
      immunodeficiency virus, including specific guidelines for discontinuing primary
      and secondary prophylaxis when immune reconstitution has occurred as a result of
      highly active antiretroviral therapies. The recommendations, developed by the U.
      S. Public Health Service and the Infectious Diseases Society of America for
      clinicians and healthcare providers, were originally published in 1995 and
      revised in 1997, 1999, and 2002. The 2002 recommendations are summarized in this
      article.

PMID- 15254444
TI  - Researching schizophrenia: the difficulty of subtyping.

PMID- 15254446
TI  - Schizophrenia risk and paternal age: a potential role for de novo mutations in
      schizophrenia vulnerability genes.
AB  - How schizophrenia (SZ) is maintained at roughly 1% of the population despite
      diminished reproduction is one puzzle currently facing researchers. De novo
      mutations were first proposed over half a century ago as a source for new SZ
      genes. Current evidence linking advancing paternal age to SZ risk makes
      revisiting this hypothesis important. Advancing paternal age is the major source
      of new mutations in the human population. This article will examine potential
      mechanisms whereby parental age may impact new mutations, as well as review
      recent data supporting such a hypothesis.

PMID- 15254448
TI  - Odor identification impairments in schizophrenia: relationship with demographic
      measures, clinical variables, and diagnostic subtypes.
AB  - Smell identification deficits are consistently found in schizophrenia (SZ), but
      little is known about the nature and characterization of this deficit or its
      relationship to the phenomenology of the illness. This study aims to further
      delineate smell identification errors in SZ by examining the relationship of
      patient demographic differences with smell-identification performance. Our
      results showed that a patient's gender and education were related to odor
      identification scores, with better performance seen in female patients and in
      those with greater educational attainment. However, there was no effect related
      to age, ethnicity, or socioeconomic status on odor identification. A smell
      identification deficit was also unrelated to clinical characteristics of the
      patients, including age at first hospitalization, number of psychiatric
      hospitalizations, and duration of illness. Odor identification also did not
      differ by SZ subtype, nor between SZ and schizoaffective disorder patients. These
      findings emphasize that odor identification deficits in SZ are unrelated to
      clinical illness features, cannot be explained by other confounds related to
      olfaction in the general population, and may be core features related to the SZ
      disease process.

PMID- 15254449
TI  - Low heart rate variability is not caused by typical neuroleptics in schizophrenia
      patients.
AB  - Both elevated cardiovascular mortality and low cardio-vagal (parasympathetic)
      heart rate variability (HRV)--a risk factor for postmyocardial infarction--are
      reported in schizophrenia (SZ). Since a number of medications have strong effects
      of cardiac conductivity, we thought it important to examine if typical
      neuroleptic medications might also affect HRV. We examined cardiac vagal activity
      during both neuroleptic treatment and a drug-free condition in seven SZ patients
      who were participating in a pilot double-blind, crossover study of placebo and
      haloperidol treatment. Twenty-four-hour Holter electrocardiograms were analyzed
      for high frequency HRV, quantitated as the percent of successive normal interbeat
      intervals greater than 50 milliseconds (PNN50), which is a good index of
      parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4+/
      9.5 versus 8.3+/-10.5; t=.22, df=6, P=.5) between the haloperidol treatment and
      drug-free conditions. Despite the elapsed time, change in medication, and altered
      clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS
      positive symptom scores declined with treatment from 12.8+/-6.5 to 8.5+/-3.5;
      paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive
      (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We
      found low cardiovagal modulation in medication-free SZ patients that was
      associated with core SZ symptoms and was unchanged by haloperidol and benztropine
      treatment. The reduced HRV in SZ patients at baseline may render them at greater
      cardiovascular risk than healthy subjects when treated with medications having
      strong cardiovascular effects.

PMID- 15254447
TI  - Could stress cause psychosis in individuals vulnerable to schizophrenia?
AB  - It has long been considered that psychosocial stress plays a role in the
      expression of symptoms in schizophrenia (SZ), as it interacts with latent neural
      vulnerability that stems from genetic liability and early environmental insult.
      Advances in the understanding of the neurobiology of the stress cascade in both
      animal and human studies lead to a plausible model by which this interaction may
      occur: through neurotoxic effects on the hippocampus that may involve synaptic
      remodeling. Of late, the neurodevelopmental model of SZ etiology has been
      favored. But an elaboration of this schema that credits the impact of postnatal
      events and considers a role for neurodegenerative changes may be more plausible,
      given the evidence for gene-environment interaction in SZ expression and
      progressive structural changes observed with magnetic resonance imaging.
      Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis,
      failure of neurogenesis, and changes in circuitry lead to an expansion of the
      time frame in which environmental effects may mediate expression of SZ symptoms.

PMID- 15254450
TI  - Are cognitive symptoms of schizophrenia mediated by abnormalities in emotional
      arousal?
AB  - We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a
      test of logical reasoning and "cognitive gating," defined as the ability to
      discriminate between relevant and irrelevant information in confirming or
      disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task
      tests both processes under neutral and affect-laden conditions. This is done by
      presenting formally identical constructs using benign and emotionally arousing
      language. When separated by symptom profiles, we found statistically significant
      differences for performance and arousal response between patients with delusions,
      patients with formal thought disorder, and patients with neither delusions nor
      formal thought disorder, as well as between patients and healthy controls. When
      analyzed by error type, we found that nearly all errors by delusional patients
      were caused by overly restrictive information choice, a pattern that may be
      related to a delusional patient's tendency to "jump to conclusions" on Bayesian
      probabilistic tasks. This is in contrast to patients with formal thought
      disorder, whose low performance resulted also from overly extensive information
      choice. The tendencies towards restriction were exacerbated by arousal, which is
      consistent with studies on cognition and arousal in healthy individuals. After
      briefly examining research on emotional arousal and SZ, and the interaction
      between emotional arousal and restriction of perceptual cues in healthy
      individuals, we conclude by suggesting a model which accounts for the distinctive
      cognitive characteristics of delusional patients by their possessing distinct
      vulnerabilities to emotional arousal. Specifically, these results suggest the
      possibility that delusional patients process information in a manner that is
      essentially intact. However, delusional patients may possess an acute
      vulnerability to emotional arousal that might cause delusional individuals to
      behave cognitively as if they were healthy individuals under significantly more
      severe forms of stress.

PMID- 15254451
TI  - Genetic testing for breast and ovarian cancer susceptibility: evaluating direct
      to-consumer marketing--Atlanta, Denver, Raleigh-Durham, and Seattle, 2003.
AB  - Breast and ovarian cancer are the second and fifth leading causes of cancer
      death, respectively, among women in the United States. One in eight women will
      have breast cancer during their lifetimes, and one in 70 will have ovarian
      cancer. Mutations in two genes, BRCA1 and BRCA2 (BRCA1/2), are associated with
      predisposition for inherited breast and ovarian cancer and are identified in 5%
      10% of women with breast or ovarian cancer (BOC). Since 1996, genetic testing for
      these mutations has been available clinically; however, population-based
      screening is not recommended because of the complexity of test interpretation and
      limited data on clinical validity and utility. Despite the test's limited
      applicability in the general population, the U.S. provider of clinical BRCA1/2
      testing (Myriad Genetic Laboratories, Inc., Salt Lake City, Utah) conducted a
      pilot direct-to-consumer (DTC) marketing campaign in two cities (Atlanta,
      Georgia, and Denver, Colorado) during September 2002-February 2003. Although DTC
      advertisements have been used to raise consumer awareness about pharmaceuticals,
      this was the first time an established genetic test was marketed to the public.
      To assess the impact of the campaign on consumer behaviors and health-care
      provider practices, CDC and the respective state health departments for the pilot
      cities and two comparison cities (Raleigh-Durham, North Carolina, and Seattle,
      Washington) surveyed consumers and providers. This report summarizes results of
      those surveys, which indicated that consumer and provider awareness of BRCA1/2
      testing increased in the pilot cities and that providers in these cities
      perceived an impact on their practice (e.g., more questions asked about testing,
      more BRCA1/2 tests requested, and more tests ordered). However, in all four
      cities, providers often lacked knowledge to advise patients about inherited BOC
      and testing. These findings underscore the need for evidence-based
      recommendations on appropriate use of genetic tests and education of providers
      and the public to achieve maximum individual and public health benefit from
      genetic testing.

PMID- 15254452
TI  - Trichinellosis associated with bear meat--New York and Tennessee, 2003.
AB  - Trichinellosis is a parasitic infection caused by tissue-dwelling Trichinella
      roundworms and is associated traditionally with ingestion of pork from infected
      domestic swine. As a result of improvements in swine production, trichinellosis
      has declined steadily in the United States. However, infection also can result
      from eating the meat of wild animals. During 1997-2001, a total of 72 cases of
      trichinellosis (median: 12 cases annually; range: 11-23 cases) were reported to
      CDC; the majority of these infections were associated with eating wild game,
      predominantly bear. This report describes three cases of trichinellosis
      associated with eating undercooked bear meat reported from New York and Tennessee
      in 2003. To prevent trichinellosis, persons should cook meat, particularly wild
      game, to an internal temperature of 160 degrees F (71 degrees C).

PMID- 15254453
TI  - Prevalence of anemia among displaced and nondisplaced mothers and children-
      Azerbaijan, 2001.
AB  - In the early 1990s, the war between Armenia and Azerbaijan over the Azeri region
      of Nagorno-Karabakh resulted in approximately 600,000 internally displaced
      persons and 200,000 refugees in Azerbaijan. After years of displacement and
      despite sustained humanitarian assistance, these internally displaced persons and
      refugees (IDP/Rs) are still coping with unfavorable living conditions and limited
      employment opportunities. Results of a 1996 CDC survey in Azerbaijan revealed
      high rates of malnutrition and anemia among both the IDP/R and resident
      populations and prompted further study of the nutritional status of these
      populations. This report summarizes results of a 2001 survey of IDP/R and non
      IDP/R mothers and children with anemia in Azerbaijan. Findings indicated that
      more than one third of mothers and children were anemic, with no significant
      difference in the overall prevalence between IDP/R and non-IDP/R populations;
      however, among the IDP/R population, anemia was associated with various
      socioeconomic factors such as education, socioeconomic status (SES), and area of
      residence. Future studies should focus on identifying causes for the high rates
      of anemia in Azerbaijan and developing effective interventions such as iron
      supplementation and behavior modification.

PMID- 15254454
TI  - West Nile virus activity United States, July 7-13, 2004.
AB  - During the week of July 7-13, a total of 30 human West Nile virus illness cases
      were reported from four states (Arizona, California, Colorado, and Iowa). During
      2004, a total of 10 states have reported a total of 108 cases of human West Nile
      virus (WNV) illness to CDC through ArboNET. Of these, 66 (61%) were reported from
      Arizona. Sixty-one (58%) of the 108 cases occurred in males; median age of
      patients was 52 years (range: 1-84 years); dates of illness onset ranged from
      April 23 to July 5; and three cases were fatal.

PMID- 15254455
TI  - Update: investigation of rabies infections in organ donor and transplant
      recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004.
AB  - On July 1, 2004, CDC reported laboratory confirmation of rabies as the cause of
      encephalitis in an organ donor and three organ recipients at Baylor University
      Medical Center (BUMC) in Dallas, Texas. Hospital and public health officials in
      Alabama, Arkansas, Oklahoma, and Texas initiated public health investigations to
      identify donor and recipient contacts, assess exposure risks, and provide rabies
      postexposure prophylaxis (PEP). As of July 9, PEP had been initiated in
      approximately 174 (19%) of 916 persons who had been assessed for exposures to the
      organ recipients or the donor. As a result of its public health investigation,
      the Arkansas Department of Health determined that the donor had reported being
      bitten by a bat (Frank Wilson, M.D., Arkansas Department of Health, personal
      communication, 2004).

PMID- 15254461
TI  - Disaster in our neighborhood: September 11, 2001.

PMID- 15254474
TI  - Relationship between indoor and outdoor levels of fine particle mass, particle
      number concentrations and black smoke under different ventilation conditions.
AB  - Fine particle mass (PM(2.5)), black smoke (BS) and particle number concentration
      (NC) were measured simultaneously indoors and outdoors at an urban location in
      Erfurt, Germany. Measurements were conducted during 2-month periods in summer and
      winter. Different ventilation modes were applied during each measurement period:
      windows closed; windows opened widely for 15 min twice per day; windows and door
      across the room opened widely for 5 min twice per day and windows tilted open all
      day long. The lowest indoor/outdoor (I/O) ratios for all pollutants were found
      for closed windows, whereas the ratios for ventilated environments were higher.
      For closed windows, the I/O ratios for PM(2.5) are larger than the corresponding
      values for BS and NC (0.63 vs. 0.44 or 0.33, respectively) probably due to lower
      penetration factors for particles sizes <500 nm and higher deposition rates for
      ultrafine particles (<100 nm). The largest differences for the I/O ratios between
      closed and tilted windows were found for NC (0.33 vs. 0.78). The indoor and
      outdoor levels of PM(2.5) and BS were strongly correlated for all ventilation
      modes. The linear regression models showed that more than 75% of the daily indoor
      variation could be explained by the daily outdoor variation for those pollutants.
      However, the correlation between indoor and outdoor NC for ventilation twice a
      day was weak. It indicates that rapid changes of the air exchange rates during
      the day may affect the correlation and regression analysis of NC indoor and
      outdoor concentrations. This effect was not observed for PM(2.5) or BS. This
      study shows the importance of the indoor air aerosol measurements for health
      effects studies and the need for more research on I/O transport mechanisms for
      NC.

PMID- 15254475
TI  - Determinants of children's exposure to environmental tobacco smoke (ETS): a study
      in Southern Germany.
AB  - Maternal smoking has been repeatedly found to be the most important determinant
      of children's exposure to environmental tobacco smoke (ETS). Here, we further
      investigated predictors for the urinary cotinine/creatinine ratio (CCR, ng/mg) in
      1220 preschool children for the year 1996. Children from smoking homes (35.1%)
      had significantly higher CCR than children from nonsmoking homes (mean: 55.5 vs.
      14.9 ng/mg). The level of education of the parents was a strong predictor for
      CCRs even after adjusting for number of cigarettes smoked, maternal smoking and
      dwelling space. Additionally, dwelling space was inversely related to children's
      urinary cotinine level. The CCR- levels in children investigated in 1996 and 1998
      were significantly correlated (Pearson's r=0.67). The parents of 806 children
      agreed for a visit to their homes. In 79 of the 536 (14.7%) of the self-reported,
      nonsmoking households, smoking was admitted during the visit. The mean urinary
      CCR of these children was 25.2 ng/mg. We conclude that in addition to parental
      smoking behaviour, other variables such as dwelling space and social and
      educational status predict the children's exposure to ETS. Our data also revealed
      that a considerable percentage of parents denied the ETS exposure of their
      children at home.

PMID- 15254476
TI  - Heterogeneity in microbial exposure in schools in Sweden, Poland and Jordan
      revealed by analysis of chemical markers.
AB  - We used gas chromatography--tandem mass spectrometry to analyze microbial
      components in 85 samples of airborne dust from schools in Jordan, Sweden, and
      Poland. To collect the samples, we allowed dust to settle on plexiglass plates
      hanging in the breathing zone in school buildings during both summer and winter.
      In each of the three countries, we conducted such sampling in two schools: one in
      an urban environment and the other in rural surroundings. The microbial marker
      profiles differed significantly between the schools and seasons. For example,
      samples from Jordan contained remarkably low levels of ergosterol (marker of
      fungal biomass) and high levels of 3-hydroxy acids (markers of
      lipopolysaccharide) of 10, 12, and 14 carbon chain lengths relative to such acids
      of 16 and 18 carbons in comparison with samples from Sweden and Poland. This
      dissimilarity in 3-hydroxy fatty acid distribution indicates significant
      differences in the populations of Gram-negative bacteria. We also noted that
      muramic acid (marker of bacterial biomass) exhibited the smallest variation
      between schools and seasons. In summary, our results demonstrate that exposure to
      microorganisms in indoor air in school buildings may differ markedly between
      countries, between seasons, and between urban and rural environments.

PMID- 15254477
TI  - The behavior and routes of lead exposure in pregrasping infants.
AB  - Understanding the routes of lead exposure in a very young infant is an essential
      precursor to identifying effective strategies for minimizing blood-lead (PbB)
      levels throughout infancy. The present study integrated observational data, lead
      loading data, and household airborne particulate levels <10 microm (PM(10)) to
      understand the broad patterns of lead exposure in infants from Port Pirie, South
      Australia. Seven, 2-19-week-old infants were observed between three and six
      times, for 3-9 h per visit, at intervals of 1-9 weeks. Household lead-loading and
      PM(10) data were collected for five of the families. Eight objects were observed
      in an infant's mouth, but only the infant's fingers, pacifier, and nipple of the
      mother's breast or teat of a bottle were observed in an infant's mouth for an
      average of more than 1% of an observation day. The objects most frequently put in
      an infant's mouth were their own fingers or their pacifier. Synthesizing our data
      on behavioral frequency, lead loading, and the surface area of contact, and using
      estimates of dose response, and sampling, transfer, and absorption efficiencies,
      the results suggest that a 4-month-old infant could absorb up to 4 microg of lead
      a day (equivalent to a PbB level of up to about 2.4 microg/dl) by mouthing their
      fingers, about two-thirds of all exposure routes identified in this study.
      Estimates also suggest that lead uptake via inhalation accounts for about 0.5-3%
      of an infant's PbB at 5 microg/dl. If our estimates reflect real routes and
      values, the majority of the average PbB level of 6-month-old infants in Port
      Pirie during 2002 could potentially be accounted for by the normal infant and
      family behaviors observed in this study. While the current level of concern is 10
      microg/dl, recent studies indicate no safe threshold for Pb exposure, and so
      interventions for reducing chronic low-level exposure are useful. We suggest that
      home-based interventions for reducing Pb exposure should focus on maintaining low
      Pb loadings on objects that are directly associated with an infant, and outside
      objects that have few transfer steps to the infant.

PMID- 15254478
TI  - Personal carbon monoxide exposure levels: contribution of local sources to
      exposures and microenvironment concentrations in Milan.
AB  - In the framework of the EXPOLIS study in Milan, Italy, 48-h carbon monoxide (CO)
      exposures of 50 office workers were monitored over a 1-year period. In this work,
      the exposures were assessed for different averaging times and were compared with
      simultaneous ambient fixed-site concentrations. The effect of gas cooking and
      smoking and different methods of commuting on the microenvironment and exposure
      levels of CO were investigated. During the sampling the subjects completed a time
      microenvironment-activity diary differentiating 11 microenvironments and three
      exposure influencing activities: gas cooking, smoking and commuting. After
      sampling, all exposure and time allocation data were stored in a relational
      database that is used in data analyses. Ambient 48-h and maximum 8-h
      distributions were similar compared to the respective personal exposures. The
      maximum 1-h personal exposures were much higher than the maximum 8-h exposures.
      The maximum 1-h exposures were as well higher than the corresponding ambient
      distribution. These findings indicate that high short-term exposures were not
      reflected in ambient monitoring data nor by long-term exposures. When gas cooking
      or smoking was present, the indoor levels at "home-" and in "other indoor"
      microenvironments were higher than without their presence. Compared with ambient
      data, the latter source was the most affective to increase the indoor levels.
      Exposure during commuting was higher than in all other microenvironments; the
      highest daily exposure contribution was found during "car/taxi" driving. Most of
      the CO exposure is acquired in indoor microenvironments. For the indoor
      microenvironments, ambient CO was the weakest predictor for "home indoor"
      concentrations, where the subjects spent most of their time, and the strongest
      for "other indoor" concentrations, where the smallest fraction of the time was
      spent. Of the main indoor sources, gas cooking, on average, significantly raised
      the indoor exposure concentrations for 45 min and tobacco smoking for 30 min. The
      highest exposure levels were experienced in street commuting. Personal exposures
      were well predicted, but 1-h maximum personal exposures were poorly predicted, by
      respective ambient air quality data. By the use of time-activity diaries, ETS
      exposure at the workplaces were probably misclassified due to differences in
      awareness to tobacco smoke between smokers and nonsmokers.

PMID- 15254479
TI  - Personal exposure to particulate matter less than 2.5 microm in Mexico City: a
      pilot study.
AB  - This study was aimed to describe the personal exposure of permanent residents in
      Mexico City's Metropolitan Area (MCMA) to particulate matter of less than 2.5
      microm diameter (PM(2.5)) during their daily activities. A total of 40 healthy
      volunteers (30 women and 10 men) with sedentary activities were included. All of
      them carried a PM(2.5) personal monitor during 13 h and registered their
      activities in a written diary that classified them in indoor and outdoor
      microenvironments in each 30 min period. All sample collections started at 0900
      hours, and even though measurements were obtained during the rainy season (April
      August 2002), the relative humidity was less than 70%. The data were categorized
      and evaluated under the following criteria: morning and afternoon exposure,
      indoor and outdoor activities, and geographical location. The descriptive
      analysis showed that the overall outdoor median concentration of PM(2.5) (89.50
      microg/m(3)) was higher than the indoor one (67.55 microg/m(3)). PM(2.5)
      concentrations in the morning to early afternoon were more elevated than in the
      late afternoon, suggesting a circadian-like behavior. In the indoor
      microenvironment, the highest concentration occurred in the subway (106.2
      microg/m(3)) followed by school (93.27 microg/m(3)), and the lowest at home (53.1
      microg/m(3)). The outdoor microenvironment with the highest concentrations was
      the public transportation (bus) (99.95 microg/m(3)), while the automobile had the
      lowest (64.9 microg/m(3)). The geographical zone with the highest concentration
      was the Center city area (87.87 microg/m(3)), and the one with the lowest
      concentration was the northeast area of the city (50 microg/m(3)). All the
      differences were statistically significant (P<0.05). Multivariate analysis
      corroborated that PM(2.5) concentrations are mainly determined by geographical
      locations and hour of the day, but not by the type of microenvironment. The
      inclusion of covariables in the multivariable analysis ensures a more accurate
      estimation and prediction of the real PM(2.5) concentrations. In conclusion,
      PM(2.5) personal exposure of healthy adult permanent residents of MCMA is usually
      higher than recommended by the international standards in outdoor and even in
      indoor microenvironments. Particulate matter personal exposure varies in relation
      to hour of the day, daily activities and microenvironments.

PMID- 15254480
TI  - Environmental tobacco smoke exposure in children: parental perception of
      smokiness at home and other factors associated with urinary cotinine in preschool
      children.
AB  - Parental smoking behavior at home and sociodemographic variables may influence
      exposure to environmental tobacco smoke (ETS) in children. A sample of 115
      preschool children aged 3-6 years was enrolled in this study. ETS exposure was
      evaluated through a questionnaire about parents' smoking behavior and
      determinations of urinary cotinine -- a biomarker of exposure -- in children.
      Bivariate and multiple regression analyses were used to evaluate the association
      between the smoking behavior of each parent at home, sociodemographic factors and
      cotinine levels in children. The parental perception of smokiness in the home was
      significantly associated with urinary cotinine in children (r-partial
      coefficient=0.324; P<0.002). The father's education, mother's smoking status, and
      day of the week when urine was sampled (Tuesday) were also independently
      associated with levels of cotinine. These four variables explained 26.4% of the
      variance in the cotinine levels of children. In designing educational programs to
      reduce passive smoking among children, it is necessary to take into account those
      factors related with cotinine levels in children. Our results support the
      influence of the mothers' smoking status, the fathers' educational level, and the
      day of the week of sampling on cotinine in children. The perception of parents
      (smokers and nonsmokers) about the smokiness in the home could also be a useful
      indicator of the cotinine in children exposed to environmental tobacco smoke in
      the household.

PMID- 15254481
TI  - Frequency of open windows in motor vehicles under varying temperature conditions:
      a videotape survey in Central North Carolina during 2001.
AB  - Air pollution exposures in the motor vehicle cabin are significantly affected by
      air exchange rate, a function of vehicle speed, window position, vent status, fan
      speed, and air conditioning use. A pilot study conducted in Houston, Texas,
      during September 2000 demonstrated that useful information concerning the
      position of windows, sunroofs, and convertible tops as a function of temperature
      and vehicle speed could be obtained through the use of video recorders. To obtain
      similar data representing a wide range of temperature and traffic conditions, a
      follow-up study was conducted in and around Chapel Hill, North Carolina at five
      sites representing a central business district, an arterial road, a low-income
      commercial district, an interstate highway, and a rural road. Each site permitted
      an elevated view of vehicles as they proceeded through a turn, thereby exposing
      all windows to the stationary camcorder. A total of 32 videotaping sessions were
      conducted between February and October 2001, in which temperature varied from 41
      degrees F to 93 degrees F and average vehicle speed varied from 21 to 77 mph. The
      resulting video tapes were processed to create a vehicle-specific database that
      included site location, date, time, vehicle type, vehicle color, vehicle age,
      window configuration, number of windows in each of three position categories
      (fully open, partially open, and closed), meteorological factors, and vehicle
      speed. Of the 4715 vehicles included in the database, 1905 (40.4%) were labeled
      as "open," indicating a window, sunroof, or convertible top was fully or
      partially open. Stepwise linear regression analyses indicated that "open" window
      status was affected by wind speed, relative humidity, vehicle speed, cloud cover,
      apparent temperature, day of week, time of day, vehicle type, vehicle age,
      vehicle color, number of windows, sunroofs, location, and air quality season.
      Open windows tended to occur less frequently when relative humidity was high,
      apparent temperature (a parameter incorporating wind chill and heat index) was
      below 50 degrees F, or the vehicle was relatively new. Although the effects of
      the identified parameters were relatively weak, they are statistically
      significant and should be considered by researchers attempting to model vehicle
      air exchange rates.

PMID- 15254482
TI  - Exposure opportunity models for Agent Orange, dioxin, and other military
      herbicides used in Vietnam, 1961-1971.
AB  - Nearly 19.5 million gallons of herbicides were sprayed on the Republic of Vietnam
      between 1961 and 1971 for military purposes. Amounts of spray and patterns of
      applications are available in an electronic file called HERBS that contains
      records of 9141 defoliation missions, including detailed coordinates of US Air
      Force Ranch Hand aircraft flight paths, along with chemical agent and gallonage
      sprayed. Two classes of models for use in epidemiological and environmental
      studies that utilize the HERBS data for estimating relative exposure opportunity
      indices are presented: a discrete "hits" model that counts instances of proximity
      in time and space to known herbicide applications, and a continuous exposure
      opportunity index, E4, that takes into account type and amount of herbicide
      sprayed, distance from spray application, and time interval when exposure may
      have occurred. Both direct spraying and indirect exposure to herbicide (or
      dioxin) that may have remained in the local environment are considered, using a
      conservative first-order model for environmental disappearance. A correction
      factor for dermal versus respiratory routes of entry has been incorporated. E4
      has a log-normal distribution that spans six orders of magnitude, thus providing
      a substantial amount of discrimination between sprayed and unsprayed areas. The
      models improve on earlier ones by making full use of the geometry of the HERBS
      spray flight paths of Ranch Hand aircraft. To the extent possible so many decades
      after the War, the models have been qualitatively validated by comparison with
      recent dioxin soil and biota samples from heavily contaminated areas of Vietnam,
      and quantitatively validated against adipose dioxin obtained in epidemiological
      studies of Vietnamese. These models are incorporated within a geographic
      information system (GIS) that may be used, as one would expect, to identify
      locations such as hamlets, villages, and military installations sprayed by
      herbicide. In a novel application, the GIS also facilitates quantitative risk
      assessment in epidemiological and ecological studies by applying the models
      within a framework of historical reconstruction of exposure history of
      individuals based upon their location histories.

PMID- 15254483
TI  - Health risk communication using comparative risk analyses.
AB  - The ability to communicate effectively the degree or magnitude of public
      exposures or health risks is essential for risk assessors and risk managers.
      Various guidelines exist for communicating environmental and public health risks,
      including recommended approaches for putting risk data into proper context.
      Although it remains unclear as to which approach is the most useful or
      appropriate under different circumstances, risk comparisons are a popular choice
      for conveying the significance of or providing a better perspective on a
      particular chemical exposure or health risk. In this paper, several different
      types of risk comparisons are described that are frequently used in the private
      and public sectors, and these are illustrated using a variety of examples from
      the literature. These approaches include: (1) intrachemical comparisons, (2)
      interchemical comparisons, (3) comparisons to background levels of risk, (4)
      comparisons to theoretical risks or safety levels, and (5) comparisons to other
      actions or activities. The primary purpose of this paper is to summarize and
      briefly discuss the advantages and limitations of these risk communication
      approaches. The evolving field of risk communication is also discussed, including
      ongoing research on public risk perceptions and alternative methods for
      communicating risk magnitudes and data uncertainties.

PMID- 15254484
TI  - Conjugated linoleic acid and obesity control: efficacy and mechanisms.
AB  - Obesity is associated with high blood cholesterol and high risk for developing
      diabetes and cardiovascular disease. Therefore, management of body weight and
      obesity are increasingly considered as an important approach to maintaining
      healthy cholesterol profiles and reducing cardiovascular risk. The present review
      addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body
      weight and composition, safety, as well as mechanisms involved in animals and
      humans. Animal studies have shown promising effects of CLA on body weight and fat
      deposition. The majority of the animal studies have been conducted using CLA
      mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12)
      and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA
      mixtures with different ratios of c9t11 and t10c12 isomers have indicated that
      the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat
      deposition. Inductions of leptin reduction and insulin resistance are the adverse
      effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain
      and fat deposition are inconsistent, and no adverse effects of CLA have been
      reported. A number of human studies suggest that CLA supplementation has no
      effect on body weight and insulin sensitivity. Although it is suggested that the
      t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on
      fat deposition are marginal and more equivocal as compared to results observed in
      animal studies. Mechanisms through which CLA reduces body weight and fat
      deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA
      include decreased energy/food intake and increased energy expenditure, decreased
      preadipocyte differentiation and proliferation, decreased lipogenesis, and
      increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and
      fat deposition in rodents, while produces less significant and inconsistent
      effects on body weight and composition in pigs and humans. New studies are
      required to examine isomer-specific effects and mechanisms of CLA in animals and
      humans using purified individual CLA isomers.

PMID- 15254485
TI  - Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF
      alpha mice.
AB  - OBJECTIVE: The role of high fat diets in breast cancer/mammary tumor (MT)
      development is controversial. This may be partially attributable to variable
      effects of high fat diets on body weight. Here, we used a moderately high fat
      diet (32.5% fat calories) expected to cause obesity in most mice, but predicted
      to result in some mice remaining in the weight range of mice fed the low fat diet
      (11% fat calories). This provided the opportunity to compare mice fed the high
      fat diet exhibiting different body weights and mice of similar weight consuming
      high vs low fat diets. EXPERIMENTAL METHODS: Transgenic MMTV-TGF-alpha mice, a
      model of postmenopausal breast cancer, consumed a low fat diet, that is, chow-fed
      (n=25) or a moderately high fat diet from 10 weeks of age (n=51). Body weight at
      34 weeks of age was used to assign high fat diet mice to obesity
      prone>overweight>obesity-resistant groups (n=17) (P<0.0001). Mice were euthanized
      when MTs developed or at 85 weeks of age. RESULTS: Final body weights were
      highest in obesity-prone>overweight >obesity-resistant=chow-fed mice. Fat pads
      and fat pad:carcass were heaviest in obesity-prone followed by overweight mice.
      However, obesity-resistant mice had fat pad weights and fat pad:carcass three
      fold greater than chow-fed mice. All groups had MT incidences between 72 and 82%.
      Obesity-prone mice exhibited the shortest MT latency (P<0.0001), but obesity
      resistant mice had significantly shorter latency than chow-fed mice. CONCLUSIONS:
      Consumption of a high fat diet increased adiposity and shortened MT latency in
      relation to its effect on body weight. These results indicate a complex role of
      dietary fat level on mammary tumorigenesis.

PMID- 15254486
TI  - Insulin resistance and weight gain in postmenopausal women of diverse ethnic
      groups.
AB  - OBJECTIVE: This study was conducted to examine the influence of insulin
      resistance on weight change in postmenopausal women of various ethnic groups.
      SUBJECTS: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic,
      and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health
      Initiative Clinical trial or Observational Study, whose blood samples were
      selected randomly from the full cohort of 161 809 women for analyses.
      MEASUREMENTS: Glucose, insulin, and lipids were measured on fasting serum samples
      drawn at baseline and after 3 y of follow-up. Weight, height, waist
      circumference, and blood pressure were measured. Physical activity and energy
      intake were assessed via questionnaire. Insulin resistance was estimated using
      the HOMA (homeostasis model) calculation. RESULTS: Average age was 62 y, average
      BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4
      kg in 3 y. In a multivariate analysis, insulin resistance and insulin
      concentrations were independent predictors of increases in weight in White women
      (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039).
      For the whole group, after adjustment for other covariates, those in the highest
      quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest
      quartile lost 0.06 kg. Similar trends were found for insulin resistance and
      weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach
      statistical significance. In Black women, no relation was seen between either
      insulin or insulin resistance and weight change. A significant interaction
      between obesity and insulin resistance was observed (P=0.002 for White women and
      0.032 for the whole group), so that there is weight gain with increasing insulin
      resistance in the leaner women, but weight loss with increasing insulin
      resistance in the most obese. CONCLUSION: Insulin resistance appears to be a
      predictor of weight gain in postmenopausal women, except for the most obese
      women. The effect is more pronounced in women who have a lower BMI, and the
      effect was not seen in the Black women who as a group had a higher BMI.

PMID- 15254487
TI  - Effects of introducing physical training in the course of a 16-week high-fat diet
      regimen on hepatic steatosis, adipose tissue fat accumulation, and plasma lipid
      profile.
AB  - OBJECTIVE: We recently reported that an 8-week high-fat diet-induced hepatic
      steatosis was completely prevented if an exercise training programme was
      introduced and pursued concurrently with the diet. The purpose of the present
      study was to determine the extent to which introducing exercise training at mid
      point in the course of a 16-week high-fat diet regimen contributes to the
      reversal of liver lipid infiltration and the reduction of blood lipid profile
      deterioration and body fat accumulation. DESIGN AND SUBJECTS: Two groups of rats
      were fed a high-fat diet (42% kcal) for 16 weeks, one remaining sedentary during
      this entire period (HF-Sed) and the other being exercise trained for the last 8
      weeks (HF-Tr). A third group was fed a standard diet and remained sedentary for
      all 16 weeks (SD-Sed). Training (5 days/week for 8 weeks) began 8 weeks after
      introducing the high-fat diet and consisted of treadmill running that was
      progressively increased to reach 60 min at 26 m/min, 10% grade, for the last 4
      weeks. MEASUREMENTS: Various parameters including liver lipid infiltration, fat
      depots and blood lipids. RESULTS: Unexpectedly, liver lipid infiltration was not
      significantly higher in HF-Sed than in SD-Sed rats (means+/-s.e.: 14.9+/-1.7 vs
      12.3+/-0.4 mg/g; P>0.05). High-fat compared to age-matched standard fed rats also
      showed an absence of difference (P>0.05) in the weight of total visceral fat pads
      (13%), plasma nonesterified fatty acids (NEFA), and leptin concentrations, but
      depicted significantly (P<0.01) higher values for subcutaneous fat pad weight and
      plasma triacyglycerol. Exercise training largely decreased visceral and
      subcutaneous fat accumulation by 30 and 26%, respectively (P<0.01) as well as
      NEFA, triacylglycerol, and leptin concentrations (P<0.01). CONCLUSION: Liver
      lipid infiltration does not seem to progress linearly over 16 weeks of high-fat
      feeding in light of what has previously been observed after 8 weeks of high-fat
      feeding. Introducing a training programme in the course of a 16-week high-fat
      diet protocol reduced adiposity, plasma NEFA, and leptin concentrations below the
      levels observed in standard fed rats. These data indicate that, exercise
      training, whether conducted concurrently or introduced during the course of a
      high-fat diet, is an asset to reduce the deleterious effects of a high-fat diet.

PMID- 15254488
TI  - Understanding the relationship between the inbreeding coefficient and multilocus
      heterozygosity: theoretical expectations and empirical data.
AB  - Geneticists have been interested in inbreeding and inbreeding depression since
      the time of Darwin. Two alternative approaches that can be used to measure how
      inbred an individual is involve the use of pedigree records to estimate
      inbreeding coefficients or molecular markers to measure multilocus
      heterozygosity. However, the relationship between inbreeding coefficient and
      heterozygosity has only rarely been investigated. In this paper, a framework to
      predict the relationship between the two variables is presented. In addition,
      microsatellite genotypes at 138 loci spanning all 26 autosomes of the sheep
      genome were used to investigate the relationship between inbreeding coefficient
      and multilocus heterozygosity. Multilocus heterozygosity was only weakly
      correlated with inbreeding coefficient, and heterozygosity was not positively
      correlated between markers more often than expected by chance. Inbreeding
      coefficient, but not multilocus heterozygosity, detected evidence of inbreeding
      depression for morphological traits. The relevance of these findings to the
      causes of heterozygosity--fitness correlations is discussed and predictions for
      other wild and captive populations are presented.

PMID- 15254489
TI  - Chromosome inheritance in triploid Pacific oyster Crassostrea gigas Thunberg.
AB  - Reproduction and chromosome inheritance in triploid Pacific oyster (Crassostrea
      gigas Thunberg) were studied in diploid female x triploid male (DT) and
      reciprocal (TD) crosses. Relative fecundity of triploid females was 13.4% of
      normal diploids. Cumulative survival from fertilized eggs to spat stage was
      0.007% for DT crosses and 0.314% for TD crosses. Chromosome number analysis was
      conducted on surviving progeny from DT and TD crosses at 1 and 4 years of age. At
      Year 1, oysters from DT crosses consisted of 15% diploids (2n=20) and 85%
      aneuploids. In contrast, oysters from TD crosses consisted of 57.2% diploids,
      30.9% triploids (3n=30) and only 11.9% aneuploids, suggesting that triploid
      females produced more euploid gametes and viable progeny than triploid males.
      Viable aneuploid chromosome numbers included 2n+1, 2n+2, 2n+3, 3n-2 and 3n-1.
      There was little change over time in the overall frequency of diploids, triploids
      and aneuploids. Among aneuploids, oysters with 2n+3 and 3n-2 chromosomes were
      observed at Year 1, but absent at Year 4. Triploid progeny were significantly
      larger than diploids by 79% in whole body weight and 98% in meat weight at 4
      years of age. Aneuploids were significantly smaller than normal diploids. This
      study suggests that triploid Pacific oyster is not completely sterile and cannot
      offer complete containment of cultured populations.

PMID- 15254490
TI  - Molecular population divergence and sexual selection on morphology in the banded
      demoiselle (Calopteryx splendens).
AB  - The importance of sexual selection in population divergence is of much interest,
      mainly because it is thought to cause reproductive isolation and hence could lead
      to speciation. Sexually selected traits have been hypothesized to diverge faster
      between populations than other traits, presumably because of differences in the
      strength, mechanism or dynamics of selection. We investigated this by quantifying
      population divergence in eight morphological characters in 12 south Swedish
      populations of a sexually dimorphic damselfly, the banded demoiselle (Calopteryx
      splendens). The morphological characters included a secondary sexual character,
      the male melanized wing spot, which has an important function in both inter- and
      intrasexual selection. In addition, we investigated molecular population
      divergence, revealed by amplified fragment length polymorphism (AFLP) analysis.
      Molecular population divergence was highly significant among these Northern
      European populations (overall F(st)=0.054; pairwise population F(st)'s ranged
      from approximately 0 to 0.13). We found evidence for isolation-by-distance
      (r=0.70) for the molecular markers and a significant correlation between
      molecular and phenotypic population divergence (r=0.39). One interpretation is
      that population divergence for the AFLP loci are affected by genetic drift, but
      is also indirectly influenced by selection, due to linkage with loci for the
      phenotypic traits. Field estimates of sexual and natural selection from two of
      the populations revealed fairly strong sexual selection on wing spot length,
      indicating that this trait has the potential to rapidly diverge, provided that
      variation is heritable and the observed selection is chronic.

PMID- 15254491
TI  - Quantitative genetic variation in an island population of the speckled wood
      butterfly (Pararge aegeria).
AB  - Evidence of changes in levels of genetic variation in the field is scarce.
      Theoretically, selection and a bottleneck may lead to the depletion of additive
      genetic variance (V(A)) but not of nonadditive, dominance variance (V(D)),
      although a bottleneck may converse V(D) to V(A). Here we analyse quantitative
      genetic variation for the Speckled Wood butterfly Pararge aegeria on the island
      of Madeira about 120 generations after first colonisation. Colonisation of the
      island involved both a bottleneck and strong natural selection, changing the
      average value of traits. Several life history and morphological traits with
      varying levels of change since colonisation were analysed. In accordance with
      expectations, all traits except one showed relatively low levels of V(A), with an
      average heritability (h(2)) of 0.078. Levels of V(D) for these traits were
      relatively high, 20-94% of total variance and on average 80% of V(G). The
      exception was a morphological trait that probably had not experienced strong
      natural selection after colonisation, for which a h(2) of 0.27 was found. Another
      interesting observation is that the population seems resistant to inbreeding
      effects, which may be the result of purging of deleterious alleles.

PMID- 15254492
TI  - Heritability of progeny size in a terrestrial isopod: transgenerational
      environmental effects on a life history trait.
AB  - Maternal effects, the environment that mothers provide to their offspring, their
      provision of nutrients and the environment that offspring of the same clutch
      share, have come to be recognized as an important influence on offspring fitness.
      In addition, in invertebrates, maternal effects and common environment may change
      according to a mother's diet. We tested for the changes in quantitative genetic
      parameters in a half-sib design where mothers were fed diets varying in nutrient
      content. Surprisingly, we found that not only maternal and common environmental
      variance changed with experimental diets but also there were significant changes
      in narrow-sense heritabilities, with corresponding h(2) values of 0.61 (high
      protein), 0.08 (high carbohydrate) and 0.001 (equal carbohydrate:protein). Our
      results show how an environmentally driven evolutionary process could occur in
      nature, since the response to selection could change dramatically according to
      the composition of the diet that females are ingesting.

PMID- 15254493
TI  - Breeding systems and continuing evolution in the endemic Sorbus taxa on Arran.
AB  - The Arran whitebeams Sorbus arranensis and S. pseudofennica are two endemic woody
      plant taxa that have evolved on Arran through hybridisation. S. arranensis is a
      triploid hybrid between the widespread diploid S. aucuparia and the rare
      tetraploid S. rupicola. S. pseudofennica is a tetraploid formed by crossing
      between S. arranensis and S. aucuparia. In order to determine the mating systems
      of the two endemic species six maternal trees of each taxon together with 10-12
      of their seed offspring were scored for their phenotype at three microsatellite
      loci and one nuclear intron locus. All seeds of S. arranensis were identical in
      phenotype to their maternal parents. In S. pseudofennica, 17.5% of all seeds
      differed in marker phenotype from their maternal parent. The proportion of seed
      with nonmaternal phenotypes varied significantly among maternal trees of S.
      pseudofennica. The results suggest that the triploid S. arranensis is an obligate
      apomict, whereas the tetraploid S. pseudofennica is a facultative apomict.
      Molecular marker analysis of three trees from Arran with an unusual leaf
      morphology indicates that they are the product of sexual reproduction by S.
      pseudofennica, and may originate from hybridisation with S. aucuparia. This
      research demonstrates that the Sorbus taxa on Arran are participants in an active
      evolutionary process generating novel biodiversity. Conservation programmes for
      these taxa should aim to preserve this evolutionary process rather than the
      individual taxonomic entities that it produces.

PMID- 15254494
TI  - Topical application of autologous serum for the treatment of late-onset aqueous
      oozing or point-leak through filtering bleb.
AB  - PURPOSE: To evaluate the efficacy of topical autologous serum application to stop
      aqueous oozing or point-leak through filtering bleb after trabeculectomy.
      PATIENTS AND METHODS: A total of 21 consecutive eyes with oozing and 21 eyes with
      a point-leak through a functional bleb after trabeculectomy with 5-fluorouracil
      or mitomycin C were enrolled in this randomized, case-control study. In eyes
      randomly assigned to the serum group, an antibiotic and the autologous serum,
      which was sterilely diluted to 20% with physiological saline, were topically
      applied four times a day for up to 12 weeks. In eyes assigned to the control
      group, the antibiotic alone was applied according to the same protocol.
      Intraocular pressure (IOP) and the presence of oozing or a point-leak were tested
      before and every 2 weeks after starting the treatments. RESULTS: In the serum and
      control groups, oozing stopped in 62.5 and 0% of eyes, respectively (P=0.003),
      and point-leaks stopped in 27.3 and 18.2%, respectively (P>0.9). IOP
      significantly increased from 10.0+/-3.2 (mean+/-standard deviation) to 11.8+/-3.3
      mmHg in eyes in which oozing stopped (P=0.066), and from 11.4+/-2.7 to 15.4+/-2.3
      mmHg in eyes in which a point-leak stopped (P=0.042). CONCLUSIONS: Autologous
      serum application was significantly effective to stop aqueous oozing but not
      point-leaks. Stopping oozing or point-leaks was significantly associated with an
      increase in IOP.

PMID- 15254495
TI  - Alphagan allergy may increase the propensity for multiple eye-drop allergy.
AB  - AIMS: Since its introduction in 1996, brimonidine tartrate 0.2% ophthalmic
      solution (Alphagan, Allergan) twice daily has become established as an effective
      intra ocular pressure-lowering treatment. While the efficacy of Alphagan cannot
      be questioned, we gained the clinical impression that the drug has an
      unacceptably high rate of allergy. Of greater concern, we suspected that patients
      suffering from local Alphagan allergy had a higher rate of allergy to
      subsequently used topical preparations. We analysed data from a large scale study
      of glaucoma patients to establish whether our suspicions were correct. SUBJECTS
      AND METHODS: We have created a database of the entire glaucoma treatment
      histories for consecutive patients attending a single consultant's clinics (DMIM)
      at Glasgow Royal Infirmary between May 1999 and September 2001. All have
      undergone medical treatment for primary open angle glaucoma, ocular hypertension,
      or normal tension glaucoma. Patients with any other form of glaucoma, and
      patients in whom a full record of treatment was not available were excluded from
      the study. RESULTS: Alphagan was discontinued due to allergy on 73 per 100,000
      patient treatment days. This was a far higher frequency than for other
      preparations. In patients allergic to both Alphagan and another preparation
      (Timoptol, Trusopt and Xalatan), the mean interval between the first and second
      allergy was shorter when Alphagan allergy occurred first. This was statistically
      significant in Timoptol and Trusopt cross-reactivity. CONCLUSIONS: Alphagan has
      high allergenicity, and may increase the likelihood of allergy to subsequently
      used preparations.

PMID- 15254496
TI  - Gelatinous drop-like corneal dystrophy in a child with developmental delay:
      clinicopathological features and exclusion of the M1S1 gene.
AB  - AIMS: Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal
      recessive condition characterised by amyloid deposits within the cornea. We
      report the histopathological and molecular genetic findings in a Caucasian child
      with GDLD who also exhibited global developmental delay. METHODS: Bilateral
      lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for
      light and electron microscopy, including immunoelectronmicroscopy. The coding
      region of the M1S1 gene was screened for mutations in the affected proband and
      available relatives, using DNA extracted from mouthwashes. RESULTS: Nodular
      deposits, which were present subepithelially and in the central superficial
      stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit
      of amyloid, together with large amounts of lactoferrin and sparse amounts of
      keratoepithelin (betaig-h3), was present in the central superficial stroma,
      causing destruction of Bowman's layer and elevation of the thinned, degenerate
      epithelium. Around the deposit zone, the stroma exhibited large numbers of thick
      filamentous proteoglycan deposits. While the affected child was homozygous for a
      novel A1133 C single-nucleotide polymorphism (SNP) that resulted in an aspartic
      acid to alanine substitution at position 173 of the M1S1 coding sequence, this
      polymorphism was also found at relatively high frequency in a sample of normal
      controls, enabling exclusion of the M1S1 gene as the disease locus. CONCLUSION:
      Increased epithelial permeability in GDLD may be explained in part by an altered
      membrane permeability of the superficial epithelial cells. An association with
      developmental delay has not been reported previously.

PMID- 15254498
TI  - Science on show in Stockholm.

PMID- 15254497
TI  - A true test of leadership.

PMID- 15254499
TI  - Aid agencies predict victory for HIV unless cash crisis is solved.

PMID- 15254500
TI  - Britain spends to secure scientific growth.

PMID- 15254501
TI  - Authors urged to come clean on competing interests.

PMID- 15254502
TI  - Bush accused of trying to foist favourites on health agency.

PMID- 15254503
TI  - Indian scientists welcome broad increase in funding.

PMID- 15254504
TI  - Institute doomed by loss of interest in basics.

PMID- 15254505
TI  - Flying labs aim to track pollution across the Atlantic.

PMID- 15254506
TI  - Political wrangling derails German university reforms.

PMID- 15254507
TI  - Funding not keeping pace with science, warns Pasteur chief.

PMID- 15254509
TI  - Science education: doing it for the kids.

PMID- 15254510
TI  - Exobiology: it's life...isn't it?

PMID- 15254511
TI  - Ocean noise could injure more than mammals.

PMID- 15254512
TI  - Edwardian anaesthetists had a finger on the pulse.

PMID- 15254513
TI  - Supplementary materials need the right format.

PMID- 15254518
TI  - Blood traffic control.

PMID- 15254519
TI  - Population ecology: a three-player solution.

PMID- 15254520
TI  - Imaging techniques: seeing single spins.

PMID- 15254521
TI  - Embryology: plane talk.

PMID- 15254523
TI  - Solar physics: hidden magnetism.

PMID- 15254522
TI  - Plant biology: good neighbours.

PMID- 15254524
TI  - Developmental biology: heading away from the rump.

PMID- 15254527
TI  - Neuropsychology: pitch discrimination in the early blind.
AB  - Do blind people develop superior abilities in auditory perception to compensate
      for their lack of vision? They are known to be better than sighted people at
      orientating themselves by sound, but it is not clear whether this enhanced
      awareness extends to other auditory domains, such as listening to music or to
      voices. Here we show that blind people are better than sighted controls at
      judging the direction of pitch change between sounds, even when the speed of
      change is ten times faster than that perceived by the controls--but only if they
      became blind at an early age. The younger the onset of blindness, the better is
      the performance, which is in line with cerebral plasticity being optimal during
      the early years.

PMID- 15254528
TI  - Fisheries: mislabelling of a depleted reef fish.
AB  - Any fish species that appears to be readily available in the marketplace will
      create an impression among the public that there is a plentiful supply of that
      fish in the sea, but this may belie the true state of the fisheries' stock. Here
      we use molecular genetic analysis to show that some three-quarters of the fish
      sold in the United States as 'red snapper'--the US Food and Drug Administration's
      legally designated common name for Lutjanus campechanus--belong to another
      species. Mislabelling to this extent not only defrauds consumers but could also
      adversely affect estimates of stock size if it influences the reporting of catch
      data that are used in fisheries management.

PMID- 15254529
TI  - The scientific impact of nations.

PMID- 15254530
TI  - Fast delivery of meteorites to Earth after a major asteroid collision.
AB  - Very large collisions in the asteroid belt could lead temporarily to a
      substantial increase in the rate of impacts of meteorites on Earth. Orbital
      simulations predict that fragments from such events may arrive considerably
      faster than the typical transit times of meteorites falling today, because in
      some large impacts part of the debris is transferred directly into a resonant
      orbit with Jupiter. Such an efficient meteorite delivery track, however, has not
      been verified. Here we report high-sensitivity measurements of noble gases
      produced by cosmic rays in chromite grains from a unique suite of fossil
      meteorites preserved in approximately 480 million year old sediments. The
      transfer times deduced from the noble gases are as short as approximately 10(5)
      years, and they increase with stratigraphic height in agreement with the
      estimated duration of sedimentation. These data provide powerful evidence that
      this unusual meteorite occurrence was the result of a long-lasting rain of
      meteorites following the destruction of an asteroid, and show that at least one
      strong resonance in the main asteroid belt can deliver material into the inner
      Solar System within the short timescales suggested by dynamical models.

PMID- 15254531
TI  - A substantial amount of hidden magnetic energy in the quiet Sun.
AB  - Deciphering and understanding the small-scale magnetic activity of the quiet
      solar photosphere should help to solve many of the key problems of solar and
      stellar physics, such as the magnetic coupling to the outer atmosphere and the
      coronal heating. At present, we can see only approximately 1 per cent of the
      complex magnetism of the quiet Sun, which highlights the need to develop a
      reliable way to investigate the remaining 99 per cent. Here we report three
      dimensional radiative transfer modelling of scattering polarization in atomic and
      molecular lines that indicates the presence of hidden, mixed-polarity fields on
      subresolution scales. Combining this modelling with recent observational data, we
      find a ubiquitous tangled magnetic field with an average strength of
      approximately 130 G, which is much stronger in the intergranular regions of solar
      surface convection than in the granular regions. So the average magnetic energy
      density in the quiet solar photosphere is at least two orders of magnitude
      greater than that derived from simplistic one-dimensional investigations, and
      sufficient to balance radiative energy losses from the solar chromosphere.

PMID- 15254532
TI  - Single spin detection by magnetic resonance force microscopy.
AB  - Magnetic resonance imaging (MRI) is well known as a powerful technique for
      visualizing subsurface structures with three-dimensional spatial resolution.
      Pushing the resolution below 1 micro m remains a major challenge, however, owing
      to the sensitivity limitations of conventional inductive detection techniques.
      Currently, the smallest volume elements in an image must contain at least 10(12)
      nuclear spins for MRI-based microscopy, or 10(7) electron spins for electron spin
      resonance microscopy. Magnetic resonance force microscopy (MRFM) was proposed as
      a means to improve detection sensitivity to the single-spin level, and thus
      enable three-dimensional imaging of macromolecules (for example, proteins) with
      atomic resolution. MRFM has also been proposed as a qubit readout device for spin
      based quantum computers. Here we report the detection of an individual electron
      spin by MRFM. A spatial resolution of 25 nm in one dimension was obtained for an
      unpaired spin in silicon dioxide. The measured signal is consistent with a model
      in which the spin is aligned parallel or anti-parallel to the effective field,
      with a rotating-frame relaxation time of 760 ms. The long relaxation time
      suggests that the state of an individual spin can be monitored for extended
      periods of time, even while subjected to a complex set of manipulations that are
      part of the MRFM measurement protocol.

PMID- 15254533
TI  - Formation of zirconium metallic glass.
AB  - Bulk metallic glasses are commonly produced by the rapid cooling of liquid
      alloys. They have emerged over the past decade as a novel class of materials,
      with attractive properties and technological promise. The bulk metallic glasses
      so far produced contain three or more component elements. These complex
      compositions are necessary to frustrate the crystallization of the liquid melt on
      cooling, but can also lead to phase separation, which is detrimental to the
      thermal and mechanical properties of metallic glasses. Here we report, using X
      ray diffraction measurements, the formation of a bulk metallic glass from
      elemental zirconium at high static pressures and low temperatures (relative to
      its melting temperature at atmospheric pressure). Amorphous zirconium can be
      recovered at ambient conditions and demonstrates a superior thermal stability
      compared to amorphous alloys, which could lead to new high-temperature
      applications of amorphous metals.

PMID- 15254534
TI  - Hydrological response to a seafloor spreading episode on the Juan de Fuca ridge.
AB  - Seafloor hydrothermal systems are known to respond to seismic and magmatic
      activity along mid-ocean ridges, often resulting in locally positive changes in
      hydrothermal discharge rate, temperature and microbial activity, and shifts in
      composition occurring at the time of earthquake swarms and axial crustal dike
      injections. Corresponding regional effects have also been observed. Here we
      present observations of a hydrological response to seafloor spreading activity,
      which resulted in a negative formation-fluid pressure transient during and after
      an earthquake swarm in the sediment-sealed igneous crust of the Middle Valley
      rift of the northernmost Juan de Fuca ridge. The observations were made with a
      borehole seal and hydrologic observatory originally established in 1991 to study
      the steady-state pressure and temperature conditions in this hydrothermally
      active area. The magnitude of the co-seismic response is consistent with the
      elastic strain that would be expected from the associated earthquakes, but the
      prolonged negative pressure transient after the swarm is surprising and suggests
      net co-seismic dilatation of the upper, permeable igneous crust. The rift valley
      was visited four weeks after the onset of the seismic activity, but no signature
      of increased hydrothermal activity was detected in the water column. It appears
      that water, not magma, filled the void left by this spreading episode.

PMID- 15254535
TI  - Cladogenesis and morphological diversification in passerine birds.
AB  - Morphological diversity tends to increase within evolving lineages over time, but
      the relative roles of gradual evolutionary change (anagenesis) and abrupt shifts
      associated with speciation events (cladogenesis, or 'punctuated equilibrium')
      have not been resolved for most groups of organisms. However, these two modes of
      evolution can be distinguished by the fact that morphological variance increases
      in proportion to time under anagenesis, and in proportion to the logarithm of the
      number of species under cladogenesis. Although species and time are themselves
      correlated, multiple regression analysis provides a statistical framework for
      partitioning their relative contributions. In this study, I use multiple
      regressions to evaluate the effects of time and species number on morphological
      diversity within clades of passerine birds. The results show clearly that number
      of species exerts a strong influence on morphological variance independent of
      time, but that time has no unique effect. Thus, morphological evolution in birds
      seems to be associated with cladogenesis. How lineage splitting promotes
      morphological diversification poses an important challenge to ecologists and
      evolutionary biologists.

PMID- 15254536
TI  - The combined effects of pathogens and predators on insect outbreaks.
AB  - The economic damage caused by episodic outbreaks of forest-defoliating insects
      has spurred much research, yet why such outbreaks occur remains unclear.
      Theoretical biologists argue that outbreaks are driven by specialist pathogens or
      parasitoids, because host-pathogen and host-parasitoid models show large
      amplitude, long-period cycles resembling time series of outbreaks. Field
      biologists counter that outbreaks occur when generalist predators fail, because
      predation in low-density defoliator populations is usually high enough to prevent
      outbreaks. Neither explanation is sufficient, however, because the time between
      outbreaks in the data is far more variable than in host-pathogen and host
      parasitoid models, and far shorter than in generalist-predator models. Here we
      show that insect outbreaks can be explained by a model that includes both a
      generalist predator and a specialist pathogen. In this host-pathogen-predator
      model, stochasticity causes defoliator densities to fluctuate erratically between
      an equilibrium maintained by the predator, and cycles driven by the pathogen.
      Outbreaks in this model occur at long but irregular intervals, matching the data.
      Our results suggest that explanations of insect outbreaks must go beyond
      classical models to consider interactions among multiple species.

PMID- 15254537
TI  - Cell fusion-independent differentiation of neural stem cells to the endothelial
      lineage.
AB  - Somatic stem cells have been claimed to possess an unexpectedly broad
      differentiation potential (referred to here as plasticity) that could be induced
      by exposing stem cells to the extracellular developmental signals of other
      lineages in mixed-cell cultures. Recently, this and other experimental evidence
      supporting the existence of stem-cell plasticity have been refuted because stem
      cells have been shown to adopt the functional features of other lineages by means
      of cell-fusion-mediated acquisition of lineage-specific determinants (chromosomal
      DNA) rather than by signal-mediated differentiation. In this study we co-cultured
      mouse neural stem cells (NSCs), which are committed to become neurons and glial
      cells, with human endothelial cells, which form the lining of blood vessels. We
      show that in the presence of endothelial cells six per cent of the NSC population
      converted to cells that did not express neuronal or glial markers, but instead
      showed the stable expression of multiple endothelial markers and the capacity to
      form capillary networks. This was surprising because NSCs and endothelial cells
      are believed to develop from the ectoderm and mesoderm, respectively. Experiments
      in which endothelial cells were killed by fixation before co-culture with live
      NSCs (to prevent cell fusion) and karyotyping analyses, revealed that NSCs had
      differentiated into endothelial-like cells independently of cell fusion. We
      conclude that stem-cell plasticity is a true characteristic of NSCs and that the
      conversion of NSCs to unanticipated cell types can be accomplished without cell
      fusion.

PMID- 15254538
TI  - The homeotic protein AGAMOUS controls microsporogenesis by regulation of
      SPOROCYTELESS.
AB  - The Arabidopsis homeotic gene AGAMOUS (AG) is necessary for the specification of
      reproductive organs (stamens and carpels) during the early steps of flower
      development. AG encodes a transcription factor of the MADS-box family that is
      expressed in stamen and carpel primordia. At later stages of development, AG is
      expressed in distinct regions of the reproductive organs. This suggests that AG
      might function during the maturation of stamens and carpels, as well as in their
      early development. However, the developmental processes that AG might control
      during organogenesis and the genes that are regulated by this factor are largely
      unknown. Here we show that microsporogenesis, the process leading to pollen
      formation, is induced by AG through activation of the SPOROCYTELESS gene (SPL,
      also known as NOZZLE,NZZ), a regulator of sporogenesis. Furthermore, we
      demonstrate that SPL can induce microsporogenesis in the absence of AG function,
      suggesting that AG controls a specific process during organogenesis by activating
      another regulator that performs a subset of its functions.

PMID- 15254539
TI  - First cleavage plane of the mouse egg is not predetermined but defined by the
      topology of the two apposing pronuclei.
AB  - Studies of experimentally manipulated embryos have led to the long-held
      conclusion that the polarity of the mouse embryo remains undetermined until the
      blastocyst stage. However, recent studies reporting that the embryonic
      abembryonic axis of the blastocyst arises perpendicular to the first cleavage
      plane, and hence to the animal-vegetal axis of the zygote, have led to the claim
      that the axis of the mouse embryo is already specified in the egg. Here we show
      that there is no specification of the axis in the egg. Time-lapse recordings show
      that the second polar body does not mark a stationary animal pole, but instead,
      in half of the embryos, moves towards a first cleavage plane. The first cleavage
      plane coincides with the plane defined by the two apposing pronuclei once they
      have moved to the centre of the egg. Pronuclear transfer experiments confirm that
      the first cleavage plane is not determined in early interphase but rather is
      specified by the newly formed topology of the two pronuclei. The microtubule
      networks that allow mixing of parental chromosomes before dividing into two may
      be involved in these processes.

PMID- 15254540
TI  - Antero-posterior tissue polarity links mesoderm convergent extension to axial
      patterning.
AB  - Remodelling its shape, or morphogenesis, is a fundamental property of living
      tissue. It underlies much of embryonic development and numerous pathologies.
      Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively
      studied model for morphogenetic processes that rely on cell rearrangement. It
      involves the intercalation of polarized cells perpendicular to the antero
      posterior (AP) axis, which narrows and lengthens the tissue. Several genes have
      been identified that regulate cell behaviour underlying CE in zebrafish and
      Xenopus. Many of these are homologues of genes that control epithelial planar
      cell polarity in Drosophila. However, elongation of axial mesoderm must be also
      coordinated with the pattern of AP tissue specification to generate a normal
      larval morphology. At present, the long-range control that orients CE with
      respect to embryonic axes is not understood. Here we show that the chordamesoderm
      of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions
      in parallel to Wnt/planar cell polarity signalling, and determines the direction
      of tissue elongation. The mechanism that establishes AP polarity involves graded
      activin-like signalling and directly links mesoderm AP patterning to CE.

PMID- 15254541
TI  - Dynamic control of positional information in the early Drosophila embryo.
AB  - Morphogen gradients contribute to pattern formation by determining positional
      information in morphogenetic fields. Interpretation of positional information is
      thought to rely on direct, concentration-threshold-dependent mechanisms for
      establishing multiple differential domains of target gene expression. In
      Drosophila, maternal gradients establish the initial position of boundaries for
      zygotic gap gene expression, which in turn convey positional information to pair
      rule and segment-polarity genes, the latter forming a segmental pre-pattern by
      the onset of gastrulation. Here we report, on the basis of quantitative gene
      expression data, substantial anterior shifts in the position of gap domains after
      their initial establishment. Using a data-driven mathematical modelling approach,
      we show that these shifts are based on a regulatory mechanism that relies on
      asymmetric gap-gap cross-repression and does not require the diffusion of gap
      proteins. Our analysis implies that the threshold-dependent interpretation of
      maternal morphogen concentration is not sufficient to determine shifting gap
      domain boundary positions, and suggests that establishing and interpreting
      positional information are not independent processes in the Drosophila
      blastoderm.

PMID- 15254542
TI  - Chromatin regulates origin activity in Drosophila follicle cells.
AB  - It is widely believed that DNA replication in multicellular animals (metazoa)
      begins at specific origins to which a pre-replicative complex (pre-RC) binds.
      Nevertheless, a consensus sequence for origins has yet to be identified in
      metazoa. Origin identity can change during development, suggesting that there are
      epigenetic influences. A notable example of developmental specificity occurs in
      Drosophila, where somatic follicle cells of the ovary transition from genomic
      replication to exclusive re-replication at origins that control amplification of
      the eggshell (chorion) protein genes. Here we show that chromatin acetylation is
      critical for this developmental transition in origin specificity. We find that
      histones at the active origins are hyperacetylated, coincident with binding of
      the origin recognition complex (ORC). Mutation of the histone deacetylase (HDAC)
      Rpd3 induced genome-wide hyperacetylation, genomic replication and a
      redistribution of the origin-binding protein ORC2 in amplification-stage cells,
      independent of effects on transcription. Tethering Rpd3 or Polycomb proteins to
      the origin decreased its activity, whereas tethering the Chameau
      acetyltransferase increased origin activity. These results suggest that
      nucleosome acetylation and other epigenetic changes are important modulators of
      origin activity in metazoa.

PMID- 15254545
TI  - Back on track?

PMID- 15254543
TI  - Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing.
AB  - Almost all DNA polymerases show a strong preference for incorporating the
      nucleotide that forms the correct Watson-Crick base pair with the template base.
      In addition, the catalytic efficiencies with which any given polymerase forms the
      four possible correct base pairs are roughly the same. Human DNA polymerase-iota
      (hPoliota), a member of the Y family of DNA polymerases, is an exception to these
      rules. hPoliota incorporates the correct nucleotide opposite a template adenine
      with a several hundred to several thousand fold greater efficiency than it
      incorporates the correct nucleotide opposite a template thymine, whereas its
      efficiency for correct nucleotide incorporation opposite a template guanine or
      cytosine is intermediate between these two extremes. Here we present the crystal
      structure of hPoliota bound to a template primer and an incoming nucleotide. The
      structure reveals a polymerase that is 'specialized' for Hoogsteen base-pairing,
      whereby the templating base is driven to the syn conformation. Hoogsteen base
      pairing offers a basis for the varied efficiencies and fidelities of hPoliota
      opposite different template bases, and it provides an elegant mechanism for
      promoting replication through minor-groove purine adducts that interfere with
      replication.

PMID- 15254546
TI  - Developing themes.

PMID- 15254548
TI  - Bricks & mortar.

PMID- 15254550
TI  - Sirtuin activators mimic caloric restriction and delay ageing in metazoans.
AB  - Caloric restriction extends lifespan in numerous species. In the budding yeast
      Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the
      sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds
      (STACs) can promote the survival of human cells and extend the replicative
      lifespan of yeast. Here we show that resveratrol and other STACs activate
      sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the
      lifespan of these animals without reducing fecundity. Lifespan extension is
      dependent on functional Sir2, and is not observed when nutrients are restricted.
      Together these data indicate that STACs slow metazoan ageing by mechanisms that
      may be related to caloric restriction.

PMID- 15254551
TI  - Planar cell polarity signalling controls cell division orientation during
      zebrafish gastrulation.
AB  - Oriented cell division is an integral part of pattern development in processes
      ranging from asymmetric segregation of cell-fate determinants to the shaping of
      tissues. Despite proposals that it has an important function in tissue
      elongation, the mechanisms regulating division orientation have been little
      studied outside of the invertebrates Caenorhabditis elegans and Drosophila
      melanogaster. Here, we have analysed mitotic divisions during zebrafish
      gastrulation using in vivo confocal imaging and found that cells in dorsal
      tissues preferentially divide along the animal-vegetal axis of the embryo.
      Establishment of this animal-vegetal polarity requires the Wnt pathway components
      Silberblick/Wnt11, Dishevelled and Strabismus. Our findings demonstrate an
      important role for non-canonical Wnt signalling in oriented cell division during
      zebrafish gastrulation, and indicate that oriented cell division is a driving
      force for axis elongation. Furthermore, we propose that non-canonical Wnt
      signalling has a conserved role in vertebrate axis elongation, orienting both
      cell intercalation and mitotic division.

PMID- 15254552
TI  - Different proliferative activity of the glandular and myoepithelial lineages in
      benign proliferative and early malignant breast diseases.
AB  - The aim of the present study was to explore cell biological characteristics of
      normal breast, benign proliferative breast diseases and noninvasive breast
      malignancies based on the recently published adult progenitor cell concept from
      our group. Here, we investigated the proliferative activity of CK5/14(+),
      CK8/18/19(+) and alpha-smooth muscle actin(+) cellular phenotypes encountered in
      normal mammary gland, in a series of usual ductal hyperplasias and early
      malignant breast diseases, such as atypical ductal and lobular hyperplasias, as
      well as ductal and lobular in situ carcinomas. Immunohistochemical double
      labeling was performed on frozen sections from diagnostic breast biopsies by
      using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins
      (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast
      tissues and usual ductal hyperplasias were characterized by a heterogeneous
      cellular composition of the growth fraction. The proliferative cell compartment
      consisted of CK8/18/19(+) glandular and, in a variable proportion, CK5/14(+)
      progenitor phenotypes. In contrast, noninvasive breast malignancies were composed
      of a monotonous proliferation of CK 8/18/19(+) neoplastic glandular cells. These
      findings indicate a significant role of progenitor cells in the development of
      benign proliferative breast diseases and lend support to the view that malignant
      transformation in the human breast usually occurs in a cell committed to the
      glandular lineage. Our results provide cell kinetic support to the functional
      progenitor cell hypothesis, and we propose this concept as an operative model for
      understanding benign proliferative and malignant breast diseases.

PMID- 15254553
TI  - Estrogen receptor beta expression in vascular neoplasia: an analysis of 53 benign
      and malignant cases.
AB  - The importance of estrogen in vascular neoplasia is suggested by a predilection
      for women and a tendency for rapid growth during pregnancy. Although early
      experiments using radioligand assays demonstrated estrogen receptor (ER)
      expression, these findings were not confirmed by subsequent immunohistochemical
      studies which were performed with antibodies raised against ER alpha. A newly
      discovered estrogen receptor subtype, ER beta, has not been previously
      characterized in vascular lesions. In order to verify the expression of estrogen
      receptors in vascular neoplasms as well as to clarify the inconsistency between
      radioligand and early immunohistochemical studies, we examined a series of 53
      benign and malignant vascular neoplasms for ER beta expression. All of the
      subtypes of vascular neoplasia examined had nuclear expression of ER beta. The
      majority of cases (94%) displayed 2+ to 3+ staining. The discrepancy between
      radioligand studies and previous immunohistochemical studies is attributable to
      the use of antibodies raised against ER alpha, which is not expressed in vascular
      lesions, and not ER beta, which is broadly expressed in both benign and malignant
      vascular neoplasms. Although ER beta may be of limited diagnostic use in vascular
      neoplasia due to its broad expression, the potential exists for a therapeutic
      approach using ER agonists.

PMID- 15254554
TI  - Aberration of epidermal growth factor receptor expression in bone and soft-tissue
      tumors: protein overexpression, gene amplification and activation of downstream
      molecules.
AB  - In order to evaluate the involvement of epidermal growth factor receptor, and to
      analyze the correlation between gene aberration and protein expression in
      mesenchymal tumors, we examined protein expression by immunohistochemistry in 125
      cases of bone and soft-tissue tumors. Furthermore, amplification of epidermal
      growth factor receptor gene was determined by fluorescence in situ hybridization.
      Positive immunostaining was found in 23 cases (18.4%). Among these 23 cases, one
      of malignant fibrous histiocytoma showed the highest degree (3+) of protein
      overexpression and gene amplification as clusters of hybridization signals,
      indicating homogeneously staining regions. The second case of malignant fibrous
      histiocytoma also showed a higher degree (2+) of overexpression and
      coamplification of the epidermal growth factor receptor gene with the centromeric
      regions, indicating polysomy of chromosome 7. The levels of expression observed
      in immunohistochemistry were confirmed by immunoblotting and found to be
      comparable. Moreover, although expression of phosphorylated epidermal growth
      factor receptor was detected in those two cases of malignant fibrous
      histiocytoma, constitutive activation of extracellular signal-related protein
      kinase 1/2 was not observed, suggesting that activation of epidermal growth
      factor receptor does not necessarily and constantly lead to signal transduction
      to the downstream molecules. In the remaining 123 cases, including 21 cases
      exhibiting weak (1+) immunoreactivity, no gene amplification nor polysomy was
      found. Collectively, expression of epidermal growth factor receptor was observed
      not infrequently in mesenchymal tumors, but 'overexpression' is rare and can be
      attributed to an increase in gene copy number, resulting from amplification or
      polysomy. Although cases that scored positive for protein expression and/or gene
      amplification could be qualified candidates for antiepidermal growth factor
      receptor therapies, further examination of the status of downstream molecules in
      the signal cascade, such as phosphorylated epidermal growth factor receptor and
      extracellular signal-related protein kinase 1/2, may be required as the process
      of therapeutic strategy.

PMID- 15254555
TI  - Isolate diffuse thickening of glomerular capillary basement membrane: a renal
      lesion in prediabetes?
AB  - A total of 23 patients with proteinuria and isolated ultrastructural diffuse
      thickening of the glomerular capillary basement membrane were studied, focusing
      on the possibility of diabetes mellitus, morphometry of the capillary basement
      membrane, and the comparison with three other groups of patients. These included
      14 patients with minimal change nephropathy (MCN), 45 patients with type II
      diabetes arbitrarily divided into 11 early and 34 late diabetic patients,
      defined, respectively, as less than 3 and over 5 years history, and 13 patients
      biopsied for transient mild proteinuria or hematuria, with no evidence of renal
      disease on follow-up were used as controls. The level of proteinuria and
      prevalence of hematuria were similar in patients with isolated thick basement
      membrane and with diabetes. Diabetic retinopathy was present in 10% of early
      diabetes, 69% of late diabetes, but not in isolated thick basement membrane.
      Kimmelstiel-Wilson nodules were seen in late diabetes, and not in other patients.
      Hyaline arteriosclerosis was more common in late diabetes than in early diabetes
      or isolated thick basement membrane. The basement membrane thickness was similar
      between controls (371+/-17 nm) and MCN (345+/-16 nm), between patients with
      isolated thick basement membrane (482+/-69 nm) and early diabetes (457+/-64 nm),
      but significantly thicker in isolated thick basement membrane as compared to
      controls and MCN. In patients with isolated thick basement membrane, the basement
      membrane thickness was not correlated with age, smoking, body weight, hyaline
      arteriosclerosis, and hypertension. However, blood tests for diabetes were
      positive in 20% of patients at biopsy, in 44% at 6 months and 70% at 24 months
      follow-up, while seven patients showed no evidence of diabetes on follow-up.
      Patients with proteinuria and isolated thick glomerular basement membrane must be
      differentiated from MCN for therapeutic implications, and specifically managed
      for its strong association with prediabetes or early diabetes.

PMID- 15254556
TI  - Kernicterus: epidemiological strategies for its prevention through systems-based
      approaches.
AB  - Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon
      disorder with tragic consequences, especially when it affects healthy term and
      near-term infants. Early identification, prevention and treatment of severe
      hyperbilirubinemia should make kernicterus a preventable disease. However,
      national epidemiologic data are needed to monitor any preventive strategies.
      Recommendations are provided to obtain prospective data on the prevalence and
      incidence of severe hyperbilirubinemia and associate mortality and neurologic
      injury using standardized definitions, explore the clinical characteristics and
      root causes of kernicterus in children identified in the Kernicterus Pilot
      Registry, identify and test an indicator for population surveillance, validating
      systems-based approaches to the management of newborn jaundice, and explore the
      feasibility of using biologic or genetic markers to identify infants at risk for
      hyperbilirubinemia. Increased knowledge about the incidence and consequences of
      severe hyperbilirubinemia is essential to the planning, implementation and
      assessment of interventions to ensure that infants discharged as healthy from
      their birth hospitals have a safer transition to home, avoiding morbidity due to
      hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference,
      key questions were raised about kernicterus and the need for additional
      strategies for its prevention. These questions and an approach to their answers
      form the basis of this report.

PMID- 15254557
TI  - Expectant management in spontaneous preterm premature rupture of membranes
      between 14 and 24 weeks' gestation.
AB  - OBJECTIVE: To examine maternal and neonatal outcomes in expectant management of
      spontaneous preterm premature rupture of membranes (PPROM) before 24 weeks. STUDY
      DESIGN: Patients presenting with spontaneous PPROM from 14 to 23 completed weeks'
      gestation between January 1, 1995 and December 31, 1999 were reviewed. A total of
      108 pregnancies were evaluated; 57 patients elected expectant management.
      RESULTS: Median latency from rupture of membranes (ROM) to delivery was 6 days;
      the overall survival rate was 26.3%. In ROM <20 weeks, a twin and a triplet
      pregnancy with loss of the presenting fetuses yielded the only survivors. In
      patients with ROM from 20 to 21 and 22 to 23 weeks, survival rates were 2/16
      (12.5%) and 11/20 (55.0%), respectively. In all, 18/57 (31.6%) of patients
      developed chorioamnionitis. There was no maternal sepsis or death. There were
      three cases of pulmonary hypoplasia, all in patients with ROM <20 weeks.
      CONCLUSIONS: Neonatal survival in spontaneous PPROM before 20 weeks is rare,
      irrespective of latency from ROM to delivery. When PPROM occurs from 20 to 24
      weeks, survival improves with increasing gestational age at ROM and at delivery.

PMID- 15254558
TI  - Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth
      weight infants <1000 g.
AB  - OBJECTIVE: To determine the growth and neurodevelopmental outcome, as well as
      predictors of the latter in extremely low-birth-weight (ELBW) infants with
      definitive necrotizing enterocolitis (NEC). STUDY DESIGN: Case - control
      analysis. In all, 17 ELBW infants <1000 g with Stage 2 or 3 NEC were matched to
      51 control infants without NEC. Demographics, clinical course, growth, and
      neurodevelopmental outcome were compared. RESULTS: Demographic and clinical
      characteristics of both groups were similar except that NEC infants had more
      culture-proven sepsis (59 vs 24%, p=0.02), longer intubation (36 vs 16 days,
      p=0.003) and longer hospital stay (134 vs 86 days, p<0.001). At 18 to 22 months
      corrected age BSID-II mental scores (MDI) were similar between groups (74+/-14 vs
      81+/-13, p=0.2). However, the psychomotor index (PDI) (66+/-18 vs 88+/-14), the
      proportion with abnormal neurologic examination (54 vs 9%), subnormal height (38
      vs 3%) and head circumference (23 vs 0%) were significantly higher in NEC infants
      (p<0.05). A logistic model identified NEC and chronic lung disease as predictors
      for abnormal PDI and MDI, respectively. CONCLUSIONS: NEC and its comorbidities
      are associated with severe neurodevelopmental and growth delay in ELBW infants.

PMID- 15254559
TI  - The Ronald McDonald House as an alternative to antepartum hospitalization.
AB  - OBJECTIVE: We sought to evaluate the use of the Ronald McDonald House (RMH) for
      selected high-risk pregnant women. METHODS: Beginning in November of 1999, women
      on the Maternal Fetal Medicine service at Albany Medical Center Hospital (AMCH)
      were candidates for antepartum lodging at the Ronald McDonald House (RMH). Women
      whose only indication for antepartum hospitalization was to maintain proximity to
      a tertiary care center were offered stays at the RMH. Antenatal and neonatal
      outcomes were reviewed. RESULTS: A total of 41 antepartum subjects stayed at the
      RMH during the study period. No adverse perinatal outcomes were identified due to
      utilization of the RMH. Patients stayed at the RMH instead of staying at AMCH as
      inpatients for a total of 586 days during the study period. CONCLUSIONS:
      Outpatient management at the RMH is a cost-effective alternative for selected
      high-risk pregnancies. No adverse outcomes in the study population were
      attributable to the utilization of the RMH.

PMID- 15254560
TI  - The possible role of intrauterine infections in unexplained second trimester
      abortions and macerated stillbirths: a study from a single center.
AB  - OBJECTIVE: To investigate the role of intrauterine infections in unexplained
      second trimester abortions and stillbirths. STUDY DESIGN: Histopathologic and
      microbiologic evidence of intrauterine infection in the placentas, fetal
      membranes and fetal lung tissues of 18 unexplained second trimester abortions and
      macerated stillbirth cases as well as the placentas and fetal membranes of 10
      healthy term neonates were investigated in a prospective study conducted in
      Ankara University School of Medicine, Turkey. RESULTS: Histopathologic
      chorioamnionitis and placental culture positivity rates in the study and control
      groups were 64.7 vs 0%. Bacteria were recovered from 90.9% of placentas and 36.4%
      of fetal lungs of the cases with histopathologic chorioamnionitis. Intrauterine
      infection was found in 66.7% of the whole study group, in 85.7% of the
      unexplained second trimester abortions, and in 54.5% of the macerated
      stillbirths. CONCLUSION: Intrauterine infection may be an important factor in
      unexplained stillbirths and second trimester abortions in centers where pregnancy
      follow-ups lack evaluation for asymptomatic infection.

PMID- 15254561
TI  - Association between lenticulostriate vasculopathy (LSV) and neonatal
      intraventricular hemorrhage (IVH).
AB  - OBJECTIVES: To determine whether there is an unconfounded association between
      neonatal intraventricular hemorrhage (IVH) and lenticulostriate vasculopathy (LSV
      (also known as thalamostriate or mineralizing vasculopathy)). STUDY DESIGN:
      During the conduct of the Magnesium and Neurologic Endpoints Trial (MagNET), a
      randomized controlled trial involving maternal, hence fetal, exposure to
      antenatal magnesium sulfate in the context of preterm labor, head ultrasounds
      were obtained for each of the surviving neonates. Because of our previous
      experience in the diagnosis of LSV, when ascertaining the presence of IVH, as
      called for by the research protocol of our study, the presence or absence of LSV
      was also determined. RESULTS: We found LSV to be relatively prevalent (10% (14 of
      140) among surviving babies). More importantly, it was significantly associated
      with the occurrence of neonatal IVH, even when controlled for possible
      confounding (adjusted OR 9.8, 95% confidence interval 1.3 to 73.1; p=0.03).
      CONCLUSION: Given the known relationships between IVH and neonatal morbidity and
      mortality, the finding of a statistically significant association between
      neonatal IVH and LSV may suggest more substantial implications for the latter
      than previously believed.

PMID- 15254562
TI  - Emergence of structural arterial stiffness in diabetes and the role of
      abnormalities of autonomic tone in the sequence of events.

PMID- 15254563
TI  - Plasma lipids and lipoproteins during first trimester in pregnant Nigerian women:
      Ilorin experience.
AB  - Thirty-two pregnant women in their first trimester with a mean age of 29.5 years,
      32 age matched non-pregnant controls were included in this study. They were bled
      after 14-hour fasting. This study was between October 2000 and October 2001.
      Plasma total cholesterol, triglyceride and HDL- cholesterol were assayed. LDL
      cholesterol was obtained through Frieldwald formula average as mean were
      calculated using Epi info version 6.0 and level of significant difference decided
      at p<0. 05. The mean age of the subjects was 9.5 years. Compared to the
      concentration in non-pregnant women [controls] the plasma level of total
      cholesterol and HDL-cholesterol were found to be significantly lower p<0.05.
      However the levels of plasma triglyceride and LDL-cholesterol were found to be
      significantly higher in the pregnant women than the control group [p<0.05]. This
      study revealed that the level of total plasma cholesterol is low in middle part
      of first trimester. We therefore suggest that in interpreting the result of total
      cholesterol in first trimester the gestation age should be put into
      consideration.

PMID- 15254564
TI  - Aerobic bacterial nosocomial infections in paediatric surgical patients at a
      tertiary health institution in Lagos, Nigeria.
AB  - This study was undertaken to determine nosocomial bacterial infections (NI) in
      surgical patients in a developing country using the detailed option of the Center
      for Disease Control (CDC) surgical patient surveillance technique. From 1994 -
      1995. Paediatrics surgical patients at the Lagos University Teaching Hospital
      (LUTH) were prospectively monitored for NI at all body sites. Standard
      definitions of NI were used, and NI sites were categorised by type of operation.
      A total of 304 NI occurred in 245 out of 664 surgical patients investigated. SSI
      (77.3 %) and urinary tract infections (19.1%) were in preponderance. Seventy
      three per cent of SSI were superficial incisions, 20.5% organ/space and 6.8% deep
      incisions. The overall wound infection rate was 30.9%. The SSI rate for emergency
      surgery was 35.6% and 26.5% for elective procedures. Rates within each wound
      class were 20.2, 23.8, 51.9 and 52.8% respectively and 17, 37.6, 43.4 and 47. 1%
      for patients with ASA scores of I II III and IV in that order. The SSI rates for
      patients with scores of 0, 1, 2 and 3 were 20.4; 43.5, 57.1 and 75% respectively.
      Mean infection rates in the various wound classes were highly correlated with the
      number of risk factors present. Klebsiella pneumoniae (38. 7%), Escherichia coli
      (22.7%), Pseudomonas aeruginosa (16.8%) and Staphylococcus aureus (10. 7%) were
      the most common pathogens.

PMID- 15254565
TI  - Diagnostic issues in cerebral malaria: a study of 112 adolescents and adults in
      Lagos, Nigeria.
AB  - OBJECTIVE: To determine the accuracy of initial diagnosis of cerebral malaria in
      adolescents and adults presenting at our tertiary centre and identify the
      clinical and laboratory parameters helpful in distinguishing cerebral malaria
      from other differential diagnosis. METHODS: A retrospective review of 112
      adolescents and adults initially diagnosed as having cerebral malaria was carried
      out. Clinical features (risk factors, mode of presentation, clinical course and
      final diagnosis) and laboratory parameters (level of parasitaemia, haematologic
      and biochemical values) were documented. RESULTS: A correct diagnosis was made in
      52 patients (46.4%), with septicaemia (20.5%) and meningitis (15.2%) accounting
      for most misdiagnosis. The majority of correctly diagnosed were aged 11-25 years
      (92.3%), and a predisposing factor was identifiable in 46.2%. Parasitaemia was
      predominantly moderate to heavy in correctly diagnosed cases, compared to those
      misdiagnosed in whom it was mild to moderate. Case fatality was higher for
      misdiagnosed cases (18.6%). CONCLUSION: The probability of an alternate diagnosis
      amenable to other treatment regimes should always be explored. This is
      particularly important in patients of middle age and those with either absent
      predisposing factors or mild parasitaemia, in order to reduce case fatality.

PMID- 15254566
TI  - Relapse precipitants in Nigerian drug abusers.
AB  - OBJECTIVE: To determine the precipitants of relapse among patients admitted to a
      Psychiatric Hospital in Nigeria for substance abuse. PATIENTS AND METHODS: A
      cross-sectional survey of consecutive admitted drug abuse patients was carried
      out at the Psychiatric Hospital, Yaba, Lagos, using Marlatt's categories to
      measure high risk situations for relapse. RESULTS: Eighty-two subjects who were
      mostly male (87.9%), never married (53.7%), privately employed (58.5%),
      professionals (32%) with mean age 31.2 (+/- 6.56) years were evaluated. Most had
      used two or three different drugs. Coping with negative emotional states or
      enhancement of positive emotions were the main reasons for relapse determinants
      given by the subjects. Substance abuse management in Nigeria should embrace
      inquiries into these emotional states during both the admission and the post
      discharge periods. CONCLUSION: Routine use of Marlatt' relapse precipitant
      categories may be helpful in designing intervention strategies to sustain
      abstinence in Nigerian drug abuser.

PMID- 15254567
TI  - Profile of and control measures for paediatric discharges against medical advice.
AB  - BACKGROUND: Children are minors in health decision- making and discharges against
      medical advice (DAMA) may portend adverse health, social and psychological
      consequences . This study was aimed at ascertaining the prevalence rate and the
      determining clinical, sociodemographic factors as well as caregivers' perceptions
      associated with paediatric DAMA with the view of proferring possible control
      measures. DESIGN: Pre-tested administered questionnaires were used to collect
      relevant data prospectively (March 2000- March 2002) from consecutive patients
      undertaking DAMA. RESULTS: Prevalence rate of DAMA was 1.2%, comprising 202 of
      16,440 discharges, of which 95 (47.0%) were neonates. Neonatal jaundice, gross
      congenital anomalies and severe birth asphyxia among neonates, and
      bronchopneumonia, gastroenteritis, malaria and malignancies among infant and
      older children,were the commonest diagnoses. Twenty (9.9%) cases were critically
      ill and 53(26.2%) were partially improved at discharge. Perceived improvement of
      illness, preference for outpatient care, financial constraints, high cost of
      hospital services, dissatisfaction and disagreements with care, were the
      commonest reasons for DAMA. CONCLUSION: DAMA is of multifactorial aetiology,
      involving clinically heterogeneous patients who may be critically ill or
      partially recovered. Socioeconomic, quality and cost of health care are
      implicated. This study recommends some control measures.

PMID- 15254568
TI  - Problems of management of burns injuries among children.
AB  - BACKGROUND: Contrary to our local experience, published data elsewhere show
      increased survival rates from major burns due to improvements in management. This
      study aimed at examining problems of burns management in children. DESIGN:
      Relevant data extracted from the records of 44 children included
      sociodemographic, clinical, management characteristics and outcomes. RESULTS:
      There were 86.0% thermal burns due to accidental, domiciliary events in 36
      (81.8%. Mean (range) BSA was 35.9% +/- 4.0 (1%-95%), mostly 2nd degree burns in
      34 (77.3%). Mean (range) duration of symptoms before presentation was 1.1 +/- 0.3
      days (1-7 days). Following hospitalisation, involvement of key experts in acute
      burns care was either delayed or omitted. Intensive care monitoring and support
      including mechanical ventilation were unavailable for 11 (25.0%) cases with
      cardiorespiratory compromise. Septicaemia & pneumonias were associated with death
      in 9 (56.3%) of the 16 deaths. Klebsiella, pseudomonas and coliform organisms
      were isolated from most burns wound. Oral acetominophen and intramuscular
      dipyrone were the main analgesics used in 24 (54.6%) and 8 (18.2%) cases
      respectively. Anxiolytics were used in only 2 94.5%). Case fatality rate was
      36.4%. Mortalities were 100% with BSA 50-100% (p=0. 000). CONCLUSION: Prevention
      and improvements in management of burns including early multidisciplinary care,
      critical care support, aggressive wound care and adequate pain control should be
      emphasised.

PMID- 15254569
TI  - Vertical facial height and proportions of face in Hausa - Fulani children in
      Northern Nigeria.
AB  - OBJECTIVE: To determine the vertical facial height and proportions of face in
      Hausa-Fulani children. MATERIALS AND METHODS: 100 subjects aged 11-13 years of
      Hausa-Fulani ancestry and with no previous orthodontic treatment were selected
      for the study. Lateral cephalometric radiographs were traced and measurements
      made to produce values for-Upper Anterior Facial Height (UAFH), Lower Anterior
      Facial Height (LAFH), Lower Posterior Facial Height (LPFH), and Total Posterior
      Facial Height (TPFH). From these measurements the various ratios were then
      derived. RESULTS: The range of normal values in both sexes for UAFH =53.1-57.8mm
      with a mean value of 55.8+/- 3.9mm: LAFH =67.6- 73.8mm with a mean value of 70.7
      4.9mm;LPFH =42.0-47.7mm with a mean of 44.7+/-4.6mm; TPFH=73.0- 80.7mm with a
      mean value of 44.7+/-4.6mm; TPFH= 73.0-80.7mm with a mean value of 76.7+/-6.0 mm.
      UAFH/TAFH was 44.2% for males and 44. 1% for females. LPFH/TPFH was constant
      (58.4%) for both sexes. TPFH/TAFH was 61.5% for males and 63.0% for females.
      CONCLUSIONS: Vertical facial height and proportions of face among Hausa-Fulani
      children differ from those of other ethnic groups and should be used in
      orthodontic diagnosis and treatment planning in Hausa-Fulani children.

PMID- 15254570
TI  - Prescription error in an orthopaedic practice.
AB  - A retrospective review of 17,833 prescription items was undertaken at the
      National Orthopaedic Hospital, Lagos, Nigeria with the aim of determining the
      prevalence and types of prescription error. The percentage prescription error was
      4.5 with type C (minor nuisance) being the most common prescription error.
      Incomplete prescription was the reason for these errors in 71% of cases. Our
      results revealed that the higher the professional status of the prescriber, the
      lower the prescription error. Even though the errors were recognised and
      corrected at the dispensing point, there was no indication that the prescriber
      was informed of his mistakes. We suggest, amongst others, regular clinical
      meeting of Doctors and Pharmacists where various aspects of rational drug could
      be discussed.

PMID- 15254571
TI  - Comparison of malocclusions and orthodontic treatment needs of handicapped and
      normal children in Ibadan using the Dental Aesthetic Index (DAI).
AB  - This study compared the prevalences of malocclusion and Orthodontic needs between
      normal Nigerian children and their handicapped counterparts using the Dental
      Aesthetic Index. The samples consisted of 1,010 children -614 normal (321 males;
      294 females) and 396 handicapped (199 males;197 females) aged 12-18 years with
      mean ages for normal and handicapped children as 14.8+/-1.9 and 15.0+/- 2.2
      respectively. They were drawn randomly from their respective schools in Ibadan,
      Nigeria. Although some differences were observed in the ten malocclusion traits
      of DAI between the normal and the handicapped children, none was found
      statistially significant (P> 0.05). Missing teeth were noted in 1.9% of the
      normal children as against 4.8% of the handicapped. Crowding of incisal segments
      was observed in 20.0% of the normal and in 21.7% of the disabled children.
      Spacing of incisal segments was recorded in 47% and 55.5% of normal and
      handicapped children respectively. Others in that order were: Disatema-31.7% and
      32.3%; Anterior maxillary irregularity - 55.5% and 40.9%; Anterior mandibular
      irregularity- 50.2% and 34.3%; Overjet - 20.7% and 13.1 %; Reversed overjet -
      1.9% and 2.3%; Open bite - 7.5% and 9.8% and total deviations from normal molar
      relation in 23.8% and 31.3%. Also, although higher proportions of handicapped
      children than the normal group were noted having DAI scores indicative of
      treatment needs ranging from elective to mandatory, no significant differences
      were noted (P>0.05). About 13% of the normal and 16% of the handicapped children
      in the study sample deserved publicly funded orthodontic care.

PMID- 15254572
TI  - Frequency and predictors of autonomic dysfunction in Parkinson's disease: a study
      of African patients in Lagos, Nigeria.
AB  - The degenerative changes in PD also affect the autonomic nervous system. The
      frequency and predictors of such involvement in Africans with PD has not been
      reported. OBJECTIVE: i) To determine the frequency and type of autonomic
      dysfunction in Nigerians with idiopathic Parkinson's disease (PD). ii) To
      determine the predictors of autonomic dysfunction in PD. METHODS: Cardiovascular
      autonomic function assessed in 33 study subjects with PD and 33 age-matched
      controls, utilising heart rate variability to deep breathing, standing and the
      Valsalva manoeuvre, and the blood pressure (BP) response to standing. The results
      were compared based on treatment category, grade of severity on the Columbia
      scale of Hoehn and Yahr, duration of PD, age at onset of PD, present age and
      occurrence of autonomic symptoms. RESULTS: Parasympathetic function was abnormal
      in 51.5% of PD subjects, significantly higher than controls (P<0.001). Of these,
      76.5% had early parasympathetic involvement and 23.5% definite parasympathetic
      involvement. Age above 65 years (at time of study or onset of PD) was the only
      clinical variable associated with parasympathetic autonomic dysfunction (p<0.05).
      Symptoms dysfunction occurred in 60.6% of PD patients and only 6.1% of controls
      (p<0. 001). There was however no demonstrable relationship between the occurrence
      of symptoms and objective evidence of autonomic dysfunction: 41.2% of PD patients
      with parasympathetic dysfunction had no symptoms. CONCLUSION: Autonomic
      dysfunction was found to be common in Africans with PD, particularly those above
      65 years and tends to affect the parasympathetic system. However, the abnormality
      may be detectable even before symptoms appear. As such, we recommend that
      cardiovascular tests of autonomic function be a routine aspect of the evaluation
      of PD patients, especially with advancing age.

PMID- 15254573
TI  - Restoration of endodontically treated teeth: a review.
AB  - The concept of restoring a pulpless tooth with post, core and/or crown is based
      on the belief that the root-filled tooth becomes brittle as a result of loss of
      moisture content. However, recent studies revealed that the moisture content of a
      root-filled tooth is not significantly different from that of a vital tooth. A
      survey of dentist' philosophies and techniques of restoring pulpless tooth
      conducted in the United States of America (U.S.A.) revealed that approximately 50
      per cent of the respondents believed that a post would reinforce an
      endodontically treated tooth, while other studies reported no statistically
      significant advantage to reinforcing the teeth. Therefore, the concept that all
      anterior teeth that have received root canal therapy require posts and crowns is
      not supported by recent studies. But the access cavity for the root canal
      treatment should be as conservative as possible so that the tooth is not weakened
      unnecessarily. Based on a review of the literature, this article intends to
      provide a guideline for the restoration of endodontically treated teeth.

PMID- 15254574
TI  - Patterns of presentation and mortality in tetanus: a 10-year retrospective
      review.
AB  - AIMS AND OBJECTIVES: To highlight the indications, problems and prospects of
      bedside non-surgically inserted jugular and subclavian dual luman catheters.
      PATIENTS AND METHODS: Renal failure patients being managed in our centre with
      indications for central catheterisation were consecutively recruited at
      presentation. They had bedside non-surgical jugular and subclavian insertion
      using modified seldinger wire technique and the performance of the Gatheters
      monitored. RESULTS: Sixteen patients aged between 23 and 65 years had 32 central
      catheterisations during the 12-month period. The indications included its use as
      haemodialysis access in all patients, additional indications were CVP monitoring
      in 5, and parenteral hyperalimentation in 1. Three catheterisations were in right
      subclavian vein, 4 in let internal jugular vein and 25 in right internal jugular
      vein. The duration of use ranged between 3 days and 11 weeks and blood flow rate
      used ranged between 50 and 350ml/min. Nine (28.1%) catheterisations were
      complicated with exit site and systemic infection. Catheter blockage and
      accidental catheter removal were recorded in 3 patients each. Carotid artery
      puncture was recorded in 2 patients but haemostasis was maintained with direct
      digital compression. CONCLUSION: We conclude that percutaneous bedside internal
      jugular and subclavian (venous) catheterisation using dual lumen catheter is safe
      and devoid of major complications. BACKGROUND: Tetanus, an ubiquitous disease
      still ravages our population despite the fact that it is totally preventable. The
      mortality had remained high with its attendant socio-economic implications as it
      affects mainly farmers in their prime of life. We conducted this retrospective
      review to be able to determine pattern of presentation, case fatality rate and
      factors influencing mortality with a view to mapping out control strategies.
      PATIENTS, MATERIALS AND METHODS: The case records of all managed patients aged 16
      and above over a ten-year period (1992-2001) were retrieved and socio-demographic
      and clinical data as well as results of laboratory investigations were collated.
      Analysis was done using SPSS package. Chi-square analysis and student t-test were
      used for comparison of means as appropriate. P-values of <0. 05 was taken as
      significant. RESULTS: There were a total of 114 patients managed during the
      period, which comprised of 85 males and 29 females. The means age (+/- SD) was
      35.96 (+/-17.76). Sixty six (57.89%) patients are either jobless or farmers.
      Majority of the patients had injuries in the lower limb 59.65% when compared with
      20.18% that had theirs in the upper limb. 107 (93.86%) of the patients presented
      with trismus while only 82 (71.93%) had opsthotonus. Only 51 (44.73%) patients
      survived while 61 (53.5%) died. The mean age (+/- SD) of the survivors was 32.35
      (+ 14.45) years while that of those that died was 39.4 (+/- 19.89) years (P =
      0.036). Other factors that significantly influenced survival included severity of
      spasms (P = 0/003), tachycardia (P = 0.044), and degree of sedation (P <0.0001).
      No association was found between survival and incubation period, period of onset,
      site of injury and associated medical conditions. CONCLUSIONS: Tetanus is still
      associated with high mortality rate. Factors such as severity of spasma, age,
      sedation and tachycardia were found to significantly influence mortality. It is
      recommended that prophylactic life immunisation against tetanus be given to all
      Nigerians.

PMID- 15254575
TI  - Care for the terminally ill: a review of deaths in the gynaecological wards of a
      tertiary institution, 1986-2000.
AB  - BACKGROUND: There is yet no formula to predict the expected date of death,
      however this information may be invaluable to the terminally ill, care givers,
      friends and family members to write the will, arrange for end-of-life care,
      settle disputes, and to make plans for burial ceremonies. OBJECTIVE: The study is
      an audit of all deaths in the gynaecological wards to determine the causes of
      death and highlight the care option for the terminally ill patient. STUDY
      METHODS: The admission ward registers and the duplicate copies of issued death
      certificates between 1986-2000 were studied. Details of the individual patients
      diagnosis and at death or discharge were collected and crosschecked with the
      patient's casenote. The collected data was subjected to statistical analysis
      using appropriate computer software. RESULTS: A total of 10,485 admissions were
      recorded in the study period. There were 89 (0.85%) deaths and 27(0.26%)
      discharges against medical advice. The yearly rate of death varied between 0.36%
      and 1.66% admissions. Patients' discharging themselves from the gynaecological
      wards against medical advice started in 1992, and was at a maximum (2.0%%) in
      1996. Carcinoma of the cervix (30.3%) was the most frequent cause of death next
      was ovarian cancer (29.2%). Death following complications from criminal abortions
      (11.2%) was fourth while deaths subsequent to operation for uterine fibroids and
      ectopic pregnancies were 2.2% each. Patients dying from complication of abortion
      were the youngest (22.6 years +/- 9.13), while patients dying from endometrial
      carcinoma were the oldest (64.75 years +/- 9.84). The mean age of patients dying
      from advance gynacological malignancies was 44.13 years +/- 17.07, which is
      significantly higher than the mean age of patients dying from complications of
      abortion, P<0.00015 (Student's T-Test, two tail, type 2). CONCLUSION: Advanced
      malignancies of the cervix, ovary and chorion carcinoma are the major causes of
      gynaecological deaths. Next, are deaths resulting from the complication of
      criminal abortion. Patients' discharge against medical advice as option of care
      needs further investigation.

PMID- 15254576
TI  - Intraorbital tuberculosis: a case report.
AB  - A 75-year-old woman presented at the eye clinic of the University of llorin
      Teaching Hospital with swelling of the left eyelids and protrusion of the left
      eyeball. The swelling was painless. Physical examination revealed no systemic
      abnormality. An incisional biopsy of the lid swelling revealed tuberculous
      orbital involvement. She responded well to anti-tuberculosis therapy, with
      regression of the lid swelling and proptosis. The importance of including
      intraorbital tuberculosis as a differential of orbital swelling in the
      environment is emphasised.

PMID- 15254577
TI  - Nonconsensual science.

PMID- 15254578
TI  - Molecular mediators of hepatic steatosis and liver injury.
AB  - Obesity and its associated comorbidities are among the most prevalent and
      challenging conditions confronting the medical profession in the 21st century. A
      major metabolic consequence of obesity is insulin resistance, which is strongly
      associated with the deposition of triglycerides in the liver. Hepatic steatosis
      can either be a benign, noninflammatory condition that appears to have no adverse
      sequelae or can be associated with steatohepatitis: a condition that can result
      in end-stage liver disease, accounting for up to 14% of liver transplants in the
      US. Here we highlight recent advances in our understanding of the molecular
      events contributing to hepatic steatosis and nonalcoholic steatohepatitis.

PMID- 15254579
TI  - Progress and problems in the biology, diagnostics, and therapeutics of prion
      diseases.
AB  - The term "prion" was introduced by Stanley Prusiner in 1982 to describe the
      atypical infectious agent that causes transmissible spongiform encephalopathies,
      a group of infectious neurodegenerative diseases that include scrapie in sheep,
      Creutzfeldt-Jakob disease in humans, chronic wasting disease in cervids, and
      bovine spongiform encephalopathy in cattle. Over the past twenty years, the word
      "prion" has been taken to signify various subtly different concepts. In this
      article, we refer to the prion as the transmissible principle underlying prion
      diseases, without necessarily implying any specific biochemical or structural
      identity. When Prusiner started his seminal work, the study of transmissible
      spongiform encephalopathies was undertaken by only a handful of scientists. Since
      that time, the "mad cow" crisis has put prion diseases on the agenda of both
      politicians and the media. Significant progress has been made in prion disease
      research, and many aspects of prion pathogenesis are now understood. And yet the
      diagnostic procedures available for prion diseases are not nearly as sensitive as
      they ought to be, and no therapeutic intervention has been shown to reliably
      affect the course of the diseases. This article reviews recent progress in the
      areas of pathogenesis of, diagnostics of, and therapy for prion diseases and
      highlights some conspicuous problems that remain to be addressed in each of these
      fields.

PMID- 15254580
TI  - Determination of the molecular basis of Marfan syndrome: a growth industry.
AB  - Although it has been known for more than a decade that Marfan syndrome - a
      dominantly inherited connective tissue disorder characterized by tall stature,
      arachnodactyly, lens subluxation, and a high risk of aortic aneurysm and
      dissection - results from mutations in the FBN1 gene, which encodes fibrillin-1,
      the precise mechanism by which the pleiotropic phenotype is produced has been
      unclear. A report in this issue now proposes that loss of fibrillin-1 protein by
      any of several mechanisms and the subsequent effect on the pool of TGF-beta may
      be more relevant in the development of Marfan syndrome than mechanisms previously
      proposed in a dominant-negative disease model. The model proposed in this issue
      demonstrates several strategies for clinical intervention.

PMID- 15254581
TI  - Unbuckling lipodystrophy from insulin resistance and hypertension.
AB  - Lipodystrophy and insulin resistance are the core features of human PPARgamma
      deficiency states. Metabolic complications in PPARgamma deficiency, such as
      hypertension, have been considered to be secondary to insulin resistance.
      However, a new mouse model that expresses the analog of a human PPARG mutation
      displays minimal lipodystrophy and insulin resistance but rather severe
      hypertension. Furthermore, the mutant protein appears to directly modulate the
      renin-angiotensin system in adipose tissue, providing evidence of the pleiotropic
      effects of PPARgamma.

PMID- 15254582
TI  - Innate immunity dictates cytokine polarization relevant to the development of
      pulmonary fibrosis.
AB  - New data support the importance of the innate immune response in the resolution
      or progression of pulmonary fibrosis. The presence of CXC chemokine receptor 3
      expressing cells, specifically pulmonary NK cells, is necessary to produce IFN
      gamma. This is critical in the polarization of the immune response to injury
      toward a favorable Th1 response and resolution. In contrast, a Th2 response is
      associated with progressive fibrosis.

PMID- 15254583
TI  - Adaptive cellular immunity in aortic aneurysms: cause, consequence, or context?
AB  - Abdominal aortic aneurysms are common and life threatening. Although CD4(+) T
      cells are abundant in aneurysm tissue, their role in disease progression remains
      unclear. A new study shows that mouse aortic allografts placed in animals lacking
      IFN-gamma receptors develop a Th2 inflammatory response with aortic aneurysms,
      whereas Th1 responses promote intimal hyperplasia. It is expected that these
      surprising findings will stimulate further efforts to clarify whether adaptive
      cellular immunity in aneurysm disease is detrimental or potentially beneficial.

PMID- 15254584
TI  - Evidence for a critical contribution of haploinsufficiency in the complex
      pathogenesis of Marfan syndrome.
AB  - Marfan syndrome is a connective tissue disorder caused by mutations in the gene
      encoding fibrillin-1 (FBN1). A dominant-negative mechanism has been inferred
      based upon dominant inheritance, mulitimerization of monomers to form
      microfibrils, and the dramatic paucity of matrix-incorporated fibrillin-1 seen in
      heterozygous patient samples. Yeast artificial chromosome-based transgenesis was
      used to overexpress a disease-associated mutant form of human fibrillin-1
      (C1663R) on a normal mouse background. Remarkably, these mice failed to show any
      abnormalities of cellular or clinical phenotype despite regulated overexpression
      of mutant protein in relevant tissues and developmental stages and direct
      evidence that mouse and human fibrillin-1 interact with high efficiency.
      Immunostaining with a human-specific mAb provides what we believe to be the first
      demonstration that mutant fibrillin-1 can participate in productive
      microfibrillar assembly. Informatively, use of homologous recombination to
      generate mice heterozygous for a comparable missense mutation (C1039G) revealed
      impaired microfibrillar deposition, skeletal deformity, and progressive
      deterioration of aortic wall architecture, comparable to characteristics of the
      human condition. These data are consistent with a model that invokes
      haploinsufficiency for WT fibrillin-1, rather than production of mutant protein,
      as the primary determinant of failed microfibrillar assembly. In keeping with
      this model, introduction of a WT FBN1 transgene on a heterozygous C1039G
      background rescues aortic phenotype.

PMID- 15254585
TI  - Human circulating AC133(+) stem cells restore dystrophin expression and
      ameliorate function in dystrophic skeletal muscle.
AB  - Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by
      widespread muscle damage that invariably leads to paralysis and death. There is
      currently no therapy for this disease. Here we report that a subpopulation of
      circulating cells expressing AC133, a well-characterized marker of hematopoietic
      stem cells, also expresses early myogenic markers. Freshly isolated, circulating
      AC133(+) cells were induced to undergo myogenesis when cocultured with myogenic
      cells or exposed to Wnt-producing cells in vitro and when delivered in vivo
      through the arterial circulation or directly into the muscles of transgenic
      scid/mdx mice (which allow survival of human cells). Injected cells also
      localized under the basal lamina of host muscle fibers and expressed satellite
      cell markers such as M-cadherin and MYF5. Furthermore, functional tests of
      injected muscles revealed a substantial recovery of force after treatment. As
      these cells can be isolated from the blood, manipulated in vitro, and delivered
      through the circulation, they represent a possible tool for future cell therapy
      applications in DMD disease or other muscular dystrophies.

PMID- 15254586
TI  - Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female
      infertility.
AB  - Since cAMP blocks meiotic maturation of mammalian and amphibian oocytes in vitro
      and cyclic nucleotide phosphodiesterase 3A (PDE3A) is primarily responsible for
      oocyte cAMP hydrolysis, we generated PDE3A-deficient mice by homologous
      recombination. The Pde3a(-/-) females were viable and ovulated a normal number of
      oocytes but were completely infertile, because ovulated oocytes were arrested at
      the germinal vesicle stage and, therefore, could not be fertilized. Pde3a(-/-)
      oocytes lacked cAMP-specific PDE activity, contained increased cAMP levels, and
      failed to undergo spontaneous maturation in vitro (up to 48 hours). Meiotic
      maturation in Pde3a(-/-) oocytes was restored by inhibiting protein kinase A
      (PKA) with adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS) or
      by injection of protein kinase inhibitor peptide (PKI) or mRNA coding for
      phosphatase CDC25, which confirms that increased cAMP-PKA signaling is
      responsible for the meiotic blockade. Pde3a(-/-) oocytes that underwent germinal
      vesicle breakdown showed activation of MPF and MAPK, completed the first meiotic
      division extruding a polar body, and became competent for fertilization by
      spermatozoa. We believe that these findings provide the first genetic evidence
      indicating that resumption of meiosis in vivo and in vitro requires PDE3A
      activity. Pde3a(-/-) mice represent an in vivo model where meiotic maturation and
      ovulation are dissociated, which underscores inhibition of oocyte maturation as a
      potential strategy for contraception.

PMID- 15254587
TI  - The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by
      impairing RANKL-induced signaling.
AB  - Highly active antiretroviral therapy (HAART), which includes HIV protease
      inhibitors (PIs), has been associated with bone demineralization. To determine if
      this complication reflects accelerated resorptive activity, we studied the impact
      of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and
      function. Surprisingly, we find that ritonavir, but not indinavir, inhibits
      osteoclast differentiation in a reversible manner and also abrogates bone
      resorption by disrupting the osteoclast cytoskeleton, without affecting cell
      number. Ritonavir given in vivo completely blunts parathyroid hormone-induced
      osteoclastogenesis in mice, which confirms that the drug is bone sparing. In
      keeping with its antiresorptive properties, ritonavir impairs receptor activator
      of nuclear factor kappaB ligand-induced (RANKL-induced) activation of NF-kappaB
      and Akt signaling pathways, both critical to osteoclast formation and function.
      In particular, ritonavir is found to inhibit RANKL-induced Akt signaling by
      disrupting the recruitment of TNF receptor-associated factor 6/c-Src complex to
      lipid rafts. Thus, ritonavir may represent a bone-sparing PI capable of
      preventing development of osteopenia in patients currently on HAART.

PMID- 15254588
TI  - Transgenic rescue of insulin receptor-deficient mice.
AB  - The role of different tissues in insulin action and their contribution to the
      pathogenesis of diabetes remain unclear. To examine this question, we have used
      genetic reconstitution experiments in mice. Genetic ablation of insulin receptors
      causes early postnatal death from diabetic ketoacidosis. We show that combined
      restoration of insulin receptor function in brain, liver, and pancreatic beta
      cells rescues insulin receptor knockout mice from neonatal death, prevents
      diabetes in a majority of animals, and normalizes adipose tissue content,
      lifespan, and reproductive function. In contrast, mice with insulin receptor
      expression limited to brain or liver and pancreatic beta cells are rescued from
      neonatal death, but develop lipoatrophic diabetes and die prematurely. These data
      indicate, surprisingly, that insulin receptor signaling in noncanonical insulin
      target tissues is sufficient to maintain fuel homeostasis and prevent diabetes.

PMID- 15254589
TI  - Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin
      resistance in normal rats.
AB  - We investigated the chronic in vivo effect of resistin on insulin sensitivity and
      glucose metabolism by overexpressing resistin protein in male Wistar rats using
      intravenous administration of an adenovirus encoding mouse resistin. After 7 days
      of elevated resistin levels at a supraphysiological concentration, the animals
      displayed glucose intolerance and hyperinsulinemia during glucose tolerance
      tests, and insulin tolerance tests demonstrated an impaired glucose-lowering
      effect of insulin. The glucose clamp studies were performed at submaximal (4
      mU/kg/min) and maximal (25 mU/kg/min) insulin infusion rates and demonstrated the
      presence of insulin resistance induced by elevated resistin levels. Indeed, the
      insulin-stimulated glucose infusion rate was decreased by 12-31%; suppression of
      hepatic glucose output was attenuated by 28-55%; and insulin suppression of
      circulating FFA levels was inhibited by 7%. Insulin receptor substrate-1 and -2
      phosphorylation and Akt activation were impaired in muscle and adipose tissue.
      Interestingly, activation of AMP-activated protein kinase in skeletal muscle,
      liver, and adipose tissue was also significantly downregulated. Together, these
      results indicate that chronic "hyper-resistinemia" leads to whole-body insulin
      resistance involving impaired insulin signaling in skeletal muscle, liver, and
      adipose tissue, resulting in glucose intolerance, hyperinsulinemia, and
      hypertriglyceridemia. Thus elevated resistin levels in normal rats fed a regular
      chow diet produce many of the features of human syndrome X.

PMID- 15254590
TI  - Role of resistin in diet-induced hepatic insulin resistance.
AB  - Resistin is an adipose-derived hormone postulated to link adiposity to insulin
      resistance. To determine whether resistin plays a causative role in the
      development of diet-induced insulin resistance, we lowered circulating resistin
      levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed
      against resistin mRNA and assessed in vivo insulin action by the insulin-clamp
      technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin
      resistance associated with an approximately 80% increase in plasma resistin
      levels. In particular, the rate of endogenous glucose production (GP) increased
      more than twofold compared with that in mice fed a standard chow. Treatment with
      the resistin ASO for 1 week normalized the plasma resistin levels and completely
      reversed the hepatic insulin resistance. Importantly, in this group of mice, the
      acute infusion of purified recombinant mouse resistin, designed to acutely
      elevate the levels of circulating resistin up to those observed in the HF-fed
      mice, was sufficient to reconstitute hepatic insulin resistance. These results
      provide strong support for a physiological role of resistin in the development of
      hepatic insulin resistance in this model.

PMID- 15254591
TI  - Hypertension and abnormal fat distribution but not insulin resistance in mice
      with P465L PPARgamma.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), the molecular
      target of a class of insulin sensitizers, regulates adipocyte differentiation and
      lipid metabolism. A dominant negative P467L mutation in the ligand-binding domain
      of PPARgamma in humans is associated with severe insulin resistance and
      hypertension. Homozygous mice with the equivalent P465L mutation die in utero.
      Heterozygous mice grow normally and have normal total adipose tissue weight.
      However, they have reduced interscapular brown adipose tissue and intra-abdominal
      fat mass, and increased extra-abdominal subcutaneous fat, compared with wild-type
      mice. They have normal plasma glucose levels and insulin sensitivity, and
      increased glucose tolerance. However, during high-fat feeding, their plasma
      insulin levels are mildly elevated in association with a significant increase in
      pancreatic islet mass. They are hypertensive, and expression of the
      angiotensinogen gene is increased in their subcutaneous adipose tissues. The
      effects of P465L on blood pressure, fat distribution, and insulin sensitivity are
      the same in both male and female mice regardless of diet and age. Thus the P465L
      mutation alone is sufficient to cause abnormal fat distribution and hypertension
      but not insulin resistance in mice. These results provide genetic evidence for a
      critical role for PPARgamma in blood pressure regulation that is not dependent on
      altered insulin sensitivity.

PMID- 15254592
TI  - Hepatitis C virus mutation affects proteasomal epitope processing.
AB  - The high incidence of hepatitis C virus (HCV) persistence raises the question of
      how HCV interferes with host immune responses. Studying a single-source HCV
      outbreak, we identified an HCV mutation that impaired correct carboxyterminal
      cleavage of an immunodominant HLA-A2-restricted CD8 cell epitope that is
      frequently recognized by recovered patients. The mutation, a conservative HCV
      nonstructural protein 3 (NS3) tyrosine to phenylalanine substitution, was absent
      in 54 clones of the infectious source, but present in 15/21 (71%) HLA-A2-positive
      and in 11/24 (46%) HLA-A2-negative patients with chronic hepatitis C. In order to
      analyze whether the mutation affected the processing of the HLA-A2-restricted CD8
      cell epitope, mutant and wild-type NS3 polypeptides were digested in vitro with
      20S constitutive proteasomes and with immunoproteasomes. The presence of the
      mutation resulted in impaired carboxyterminal cleavage of the epitope. In order
      to analyze whether impaired epitope processing affected T cell priming in vivo,
      HLA-A2-transgenic mice were infected with vaccinia viruses encoding either wild
      type or mutant HCV NS3. The mutant induced fewer epitope-specific, IFN-gamma;
      producing and fewer tetramer(+) cells than the wild type. These data demonstrate
      how a conservative mutation in the flanking region of an HCV epitope impairs the
      induction of epitope-specific CD8(+) T cells and reveal a mechanism that may
      contribute to viral sequence evolution in infected patients.

PMID- 15254593
TI  - Apolipoprotein A-IV inhibits experimental colitis.
AB  - The antiatherogenic properties of apoA-IV suggest that this protein may act as an
      anti-inflammatory agent. We examined this possibility in a mouse model of acute
      colitis. Mice consumed 3% dextran sulfate sodium (DSS) in their drinking water
      for 7 days, with or without daily intraperitoneal injections of recombinant human
      apoA-IV. apoA-IV significantly and specifically delayed the onset, and reduced
      the severity and extent of, DSS-induced inflammation, as assessed by clinical
      disease activity score, macroscopic appearance and histology of the colon, and
      tissue myeloperoxidase activity. Intravital fluorescence microscopy of colonic
      microvasculature revealed that apoA-IV significantly inhibited DSS-induced
      leukocyte and platelet adhesive interactions. Furthermore, apoA-IV dramatically
      reduced the upregulation of P-selectin on colonic endothelium during DSS-colitis.
      apoA-IV knockout mice exhibited a significantly greater inflammatory response to
      DSS than did their WT littermates; this greater susceptibility to DSS-induced
      inflammation was reversed upon exogenous administration of apoA-IV to knockout
      mice. These results provide the first direct support for the hypothesis that apoA
      IV is an endogenous anti-inflammatory protein. This anti-inflammatory effect
      likely involves the inhibition of P-selectin-mediated leukocyte and platelet
      adhesive interactions.

PMID- 15254594
TI  - Inhibition of experimental asthma by indoleamine 2,3-dioxygenase.
AB  - Epidemiological evidence points to the inverse relationship between microbial
      exposure and the prevalence of allergic asthma and autoimmune diseases in
      Westernized countries. The molecular basis for this observation has not yet been
      completely delineated. Here we report that the administration of certain toll
      like receptor (TLR) ligands, via the activation of innate immunity, induces high
      levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of
      tryptophan catabolism in various organs. TLR9 ligand-induced pulmonary IDO
      activity inhibits Th2-driven experimental asthma. IDO activity expressed by
      resident lung cells rather than by pulmonary DCs suppressed lung inflammation and
      airway hyperreactivity. Our results provide a mechanistic insight into the
      various formulations of the hygiene hypothesis and underscore the notion that
      activation of innate immunity can inhibit adaptive Th cell responses.

PMID- 15254595
TI  - Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in
      tumor-draining lymph nodes.
AB  - One mechanism contributing to immunologic unresponsiveness toward tumors may be
      presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor
      draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that
      constitutively expressed immunosuppressive levels of the enzyme indoleamine 2,3
      dioxygenase (IDO). Despite comprising only 0.5% of LN cells, these pDCs in vitro
      potently suppressed T cell responses to antigens presented by the pDCs themselves
      and also, in a dominant fashion, suppressed T cell responses to third-party
      antigens presented by nonsuppressive APCs. Adoptive transfer of DCs from TDLNs
      into naive hosts created profound local T cell anergy, specifically toward
      antigens expressed by the transferred DCs. Anergy was prevented by targeted
      disruption of the IDO gene in the DCs or by administration of the IDO inhibitor
      drug 1-methyl-D-tryptophan to recipient mice. Within the population of pDCs, the
      majority of the functional IDO-mediated suppressor activity segregated with a
      novel subset of pDCs coexpressing the B-lineage marker CD19. We hypothesize that
      IDO-mediated suppression by pDCs in TDLNs creates a local microenvironment that
      is potently suppressive of host antitumor T cell responses.

PMID- 15254598
TI  - Pseudolabor: A New Conversion Disorder Subtype? A Case Presentation and
      Literature Review.
AB  - Pseudolabor is not a recognized conversion disorder subtype. The diagnosis of
      conversion disorder is suspected when a patient presents with symptoms under
      voluntary control that mimic a neurologic or medical condition. The term
      pseudolabor was first used in 1994 to describe a patient who presented at 27
      weeks' gestation with monitored contraction activity and no palpable uterine
      contractions. A second case is presented herein. Both patients were initially
      managed as though they had preterm labor or uterine irritability with minimal
      cervical changes. The diagnosis was suspected only after each patient failed to
      respond to aggressive tocolysis. On external tocodynamometry, contractions were
      abrupt in onset and abrupt in descent. Only after palpating abdominal
      contractions and not uterine contractions did the attending physicians make the
      correct diagnosis. The development of pseudolabor in a patient with previously
      diagnosed pseudoseizures suggests that the condition was conversion disorder. The
      prevalence of pseudolabor is unknown and may be underestimated: electronic fetal
      monitoring has minimized the need to palpate uterine contractions in the laboring
      patient. The diagnosis of pseudolabor as a subtype of conversion disorder should
      be considered in any patient who presents with recurrent preterm uterine
      contractions, no (or minimal) cervical changes, and an atypical contraction
      pattern.

PMID- 15254596
TI  - Regulation of pulmonary fibrosis by chemokine receptor CXCR3.
AB  - CXC chemokine receptor 3 (CXCR3) is the receptor for the IFN-gamma-inducible C-X
      C chemokines MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. CXCR3 is expressed on
      activated immune cells and proliferating endothelial cells. The role of CXCR3 in
      fibroproliferation has not been investigated. We examined the role of CXCR3 in
      pulmonary injury and repair in vivo. CXCR3-deficient mice demonstrated increased
      mortality with progressive interstitial fibrosis relative to WT mice. Increased
      fibrosis occurred without increased inflammatory cell recruitment. CXCR3
      deficiency resulted in both a reduced early burst of IFN-gamma production and
      decreased expression of CXCL10 after lung injury. We identified a relative
      deficiency in lung NK cells in the unchallenged CXCR3-deficient lung and
      demonstrated production of IFN-gamma by WT lung NK cells in vivo following lung
      injury. The fibrotic phenotype in the CXCR3-deficient mice was significantly
      reversed following administration of exogenous IFN-gamma or restoration of
      endogenous IFN-gamma production by adoptive transfer of WT lymph node and spleen
      cells. Finally, pretreatment of WT mice with IFN-gamma-neutralizing Ab's enhanced
      fibrosis following lung injury. These data demonstrate a nonredundant role for
      CXCR3 in limiting tissue fibroproliferation and suggest that this effect may be
      mediated, in part, by the innate production of IFN-gamma following lung injury.

PMID- 15254597
TI  - Th2-predominant inflammation and blockade of IFN-gamma signaling induce aneurysms
      in allografted aortas.
AB  - Abdominal aortic aneurysms (AAAs) cause death due to complications related to
      expansion and rupture. The underlying mechanisms that drive AAA development
      remain largely unknown. We recently described evidence for a shift toward T
      helper type 2 (Th2) cell responses in human AAAs compared with stenotic
      atheromas. To evaluate putative pathways in AAA formation, we induced Th1- or Th2
      predominant cytokine environments in an inflammatory aortic lesion using murine
      aortic transplantation into WT hosts or those lacking the receptors for the
      hallmark Th1 cytokine IFN-gamma, respectively. Allografts in WT recipients
      developed intimal hyperplasia, whereas allografts in IFN-gamma receptor-deficient
      (GRKO) hosts developed severe AAA formation associated with markedly increased
      levels of MMP-9 and MMP-12. Allografts in GRKO recipients treated with anti-IL-4
      antibody to block the characteristic IL-4 Th2 cytokine or allografts in GRKO
      hosts also congenitally deficient in IL-4 did not develop AAA and likewise
      exhibited attenuated collagenolytic and elastolytic activities. These
      observations demonstrate an important dichotomy between cellular immune responses
      that induce IFN-gamma- or IL-4-dominated cytokine environments. The findings
      establish important regulatory roles for a Th1/Th2 cytokine balance in modulating
      matrix remodeling and have important implications for the pathophysiology of AAAs
      and arteriosclerosis.

PMID- 15254599
TI  - Urinary Side Effects of Duloxetine in the Treatment of Depression and Stress
      Urinary Incontinence.
AB  - BACKGROUND: The efficacy and safety of duloxetine, a dual reuptake inhibitor of
      serotonin and norepinephrine at the recommended starting dose, have been
      demonstrated in the treatment of major depressive disorder (MDD) in men and women
      and in the treatment of stress urinary incontinence (SUI) in women. Since the
      mechanism of action of duloxetine in the treatment of SUI is believed to be
      related to enhanced urethral closure forces, it is important to clarify the risk
      of acute urinary retention. METHOD: The relationship between duloxetine and
      obstructive voiding symptoms was examined in 8 double-blind, 8- to 9-week,
      placebo-controlled studies and 1 open-label study in men and women treated for
      MDD with duloxetine 40 to 120 mg/day and in 4 double-blind, 12-week, placebo
      controlled studies and 4 ongoing open-label studies in women treated for SUI with
      duloxetine 80 mg/day. RESULTS: In 378 men and 761 women with MDD treated in
      placebo-controlled trials, 0.4% (4/1139; 3 men and 1 woman) of those treated with
      active medication reported subjective urinary retention versus none (0/777) of
      those treated with placebo (p =.15). In 958 women with SUI treated with
      duloxetine in placebo-controlled trials, none reported subjective urinary
      retention. Overall, in the duloxetine placebo-controlled clinical studies in the
      treatment of MDD and SUI, obstructive voiding symptoms (reported either as
      subjective urinary retention or other obstructive voiding symptoms) occurred more
      often in patients receiving duloxetine (1.0%, 20/2097) than in patients receiving
      placebo (0.4%, 6/1732) (p <.05). Of the 4719 MDD and SUI patients treated with
      duloxetine in placebo-controlled and ongoing open-label studies, 2 men and 1
      woman discontinued because of obstructive voiding symptoms. Although such an
      evaluation was not required by protocol, no cases of objective acute urinary
      retention with postvoid residual urine verified with a bladder scan or requiring
      catheterization were reported in patients treated with duloxetine. CONCLUSION:
      Duloxetine treatment in women and men with depression and in women with SUI was
      rarely associated with obstructive voiding symptoms, and no subjects had
      objective acute urinary retention requiring catheterization.

PMID- 15254600
TI  - Prevalence of Metabolic Syndrome in Hispanic and Non-Hispanic Patients With
      Schizophrenia.
AB  - BACKGROUND: Metabolic syndrome, a constellation of truncal obesity, dyslipidemia,
      disturbed insulin and glucose metabolism, and hypertension, is associated with
      the development of diabetes mellitus and coronary heart disease. However, the
      prevalence of metabolic syndrome in Hispanic patients with schizophrenia and
      whether they differ from comparable non-Hispanic patients is uncertain. METHOD:
      This cross-sectional study, conducted from January 2002 to May 2002, included 48
      patients with schizophrenia who were recruited from an outpatient psychiatric
      clinic. Metabolic syndrome was defined using the criteria of the Third Report of
      the National Cholesterol Education Program Expert Panel on Detection, Evaluation,
      and Treatment of High Blood Cholesterol in Adults. RESULTS: The prevalence of
      metabolic syndrome was 63% in all patients with schizophrenia. The metabolic
      syndrome was present in 41% of non-Hispanic patients and in 74% of Hispanic
      patients with schizophrenia. Metabolic syndrome was present in 70% of Cuban
      Americans and 88% of other Hispanic subgroups with schizophrenia. Metabolic
      syndrome was associated with waist circumference (p <.05) and high-density
      lipoprotein cholesterol (p <.05) in logistic regression analysis. CONCLUSIONS:
      These data suggest that schizophrenic patients have a 3-fold greater risk to
      develop metabolic syndrome than the general population. Hispanic schizophrenic
      patients have a significantly greater prevalence of metabolic syndrome than non
      Hispanic schizophrenic patients (p <.05). An increased waist circumference is the
      strongest clinical correlate with metabolic syndrome in schizophrenic patients.

PMID- 15254601
TI  - Suicidality as a Possible Side Effect of Antidepressant Treatment.
AB  - PHYSICIANS RESPOND TO THE FDA PUBLIC HEALTH ADVISORY ON WORSENING DEPRESSION AND
      SUICIDALITY IN PATIENTS BEING TREATED WITH ANTIDEPRESSANTS: On March 22, 2004,
      the U.S. Food and Drug Administration (FDA) issued a health advisory informing
      the public that manufacturers of several popular antidepressants have been asked
      to include a warning statement on product labeling. This warning statement
      recommends that antidepressant-treated patients-both children and adults-should
      be closely monitored for worsening of depression or emergence of suicidal
      behavior. The full text of the advisory, along with supporting information and
      presentations from the February 2004 meeting on which this advisory was based,
      can be found on the FDA's Web site at
      http://www.fda.gov/cder/drug/antidepressants/default.htm. Recently, the CME
      Institute, as a service to its members-you, the readers of this journal-and Larry
      Culpepper, M.D., Editor in Chief of the Primary Care Companion, assembled a group
      of psychiatrists and primary care physicians to discuss the FDA advisory and
      advise clinicians how it will affect their treatment of depressed patients. Their
      discussion and recommendations appear here. Faculty affiliations and disclosures
      appear at the end of this Commentary.

PMID- 15254602
TI  - How Brief Can Effective Psychotherapy Be?

PMID- 15254603
TI  - How Do You Code "Annoying Family Member"?

PMID- 15254604
TI  - Atomoxetine Used Adjunctively With Selective Serotonin Reuptake Inhibitors to
      Treat Depression.

PMID- 15254605
TI  - Adult Asthma Consensus Guidelines update 2003.
AB  - BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management
      of asthma have been published over the past 15 years. Since the last revision of
      the 1999 Canadian Asthma Consensus Report, important new studies have highlighted
      the need to incorporate new information into the asthma guidelines. OBJECTIVES:
      To review the literature on adult asthma management published between January
      2000 and June 2003; to evaluate the influence of the new evidence on the
      recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its
      2001 update; and to report new recommendations on adult asthma management.
      METHODS: Three specific topics for which new evidence affected the previous
      recommendations were selected for review: initial treatment of asthma, add-on
      therapies in the treatment of asthma and asthma education. The resultant reviews
      were discussed in June 2003 at a meeting under the auspices of the Canadian
      Thoracic Society, and recommendations for adult asthma management were reviewed.
      RESULTS: The present report emphasises the importance of the early introduction
      of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the
      benefit of adding additional therapy, preferably long-acting beta2-agonists, to
      patients incompletely controlled on low doses of inhaled corticosteroids; and
      documents the essential role of asthma education. CONCLUSION: The present report
      generally supports many of the previous recommendations published in the 1999
      Canadian Asthma Consensus Report and provides higher levels of evidence for a
      number of those recommendations.

PMID- 15254607
TI  - Trouble in Anatolia.

PMID- 15254608
TI  - Musings of a political neophyte.

PMID- 15254609
TI  - Tuberculous lymphadenitis in Manitoba: incidence, clinical characteristics and
      treatment.
AB  - BACKGROUND: Tuberculous lymphadenitis (TBL) is an important form of
      extrapulmonary tuberculosis (TB). Recent studies have shown an increase in TBL in
      Canada. OBJECTIVES: To determine the incidence of TBL in Manitoba and to identify
      the characteristics associated with its presentation, diagnosis and treatment
      METHODS: Population data from the Manitoba Health Population Registry, the First
      Nations and Inuit Health Branch of Health Canada, and Statistics Canada were used
      to calculate incidence. Case characteristics and outcomes were determined by a
      systematic, retrospective review of all cases between January 1, 1990 and
      December 31, 2000. RESULTS: One-hundred forty seven cases of TBL were identified
      during the study period; 77% confirmed by culture; 68% women. TBL was found in
      Canadian-born/nonstatus Aboriginal (12%), status Aboriginal (29%) and foreign
      born (59%) populations. Incidence of TBL was 1.17 per 100,000 person years (95%
      CI 0.98 to 1.36). The highest incidence was in status Aboriginals over 65 years
      (16.85 per 100,000 person years; 95% CI 3.37 to 30.33). TBL is seen most often in
      Western Pacific women. The most common presentation was a single, enlarged
      cervical node (80%). No atypical mycobacterium was found. Drug resistance
      occurred in 13% of cases and only in the foreign-born. Cure rates (81%) were
      influenced by comorbidity and burden of TB disease. Relapse occurred in 8.1 per
      1000 person years of follow-up (95% CI 1.7 to 23.7). CONCLUSIONS: Respiratory
      physicians, who manage the majority of TB disease in Canada, need to remain aware
      that TB is an important and treatable cause of enlarged lymph nodes.

PMID- 15254610
TI  - Evaluation of malignant mesothelioma in central Anatolia: a study of 67 cases.
AB  - BACKGROUND: Malignant mesothelioma (MM) is a fatal neoplasm which frequently
      results from exposure to asbestos or erionite. METHOD: Sixty-seven patients with
      MM were seen between 1990 and 2001. Their clinical and radiological features, as
      well as the therapy, were retrospectively evaluated. RESULTS: In 51 patients
      (76.1%), the MM was confined to the pleura, in 14 patients it was exclusively
      peritoneal and in two patients, it involved both areas. Of the 67 cases, 35
      (52.2%) were women. The mean (+/- SD) age for all cases was 57.6+/-11.5 years.
      Dyspnea (67.2%), cough (55.2%) and chest pain (50.7%) were the most frequent
      symptoms of onset. Pleural effusion (92.4%) was the most common chest x-ray
      finding, whereas pleural effusion (60.8%), pleural nodules (34.7%) and pleural
      thickening (34.7%) were the most common computed tomography findings in pleural
      MM patients. The histological subtypes of MM were determined as epithelial in 60
      patients (89.5%), sarcomatous in four patients (5.9%) and mixed in three patients
      (4.4%). Although 50.7% and 25.4% of the cases were exposed to erionite and
      asbestos, respectively, 23.9% of the cases recalled no exposure to asbestos or
      erionite. Exposures were environmental as opposed to occupational. Thirty-five
      patients (52.2%) were administered chemotherapy, and follow-up data were
      available for 22 patients. For these patients, the two-year survival rate was 22%
      and the two-year progression-free interval was 15.7%. There were no differences
      between patients with asbestos and erionite exposure. CONCLUSION: MM should be
      considered when exudative pleural effusion is detected in a patient who has been
      exposed to asbestos or erionite. MM is a major public health problem in parts of
      Turkey and compulsory environmental control of fibrous mineral should be
      considered.

PMID- 15254611
TI  - Outcomes of asthma education: results of a multisite evaluation.
AB  - BACKGROUND: This observational study compared the effectiveness of a standardized
      adult asthma education program administered in a variety of sites and practice
      settings on health care utilization, absenteeism, amount of leisure time missed
      and quality of life (using the Medical Outcomes Study 36-Item Short Form 1.0 [SF
      36]). METHODS: Seven asthma centres participated in an uncontrolled, multicentre,
      prospective, observational study using a pre-post design. Variables included
      hospital- and community-based centres, an academic hospital setting and the
      presence or absence of physician attendance. Trained asthma educators
      administered a guided self- management education program, and standardized
      questionnaires were used for patient assessment at baseline and six months after
      education. RESULTS: Of the 517 patients enrolled at baseline, 396 were eligible
      for the six-month follow-up. Follow-up data were available for 252 patients. SF
      36 data were collected for 241 patients at six sites, with follow-up data
      available for 103 of 155 eligible patients. Asthma education was associated with
      substantial improvements in scheduled and unscheduled physician visits,
      unscheduled specialist visits, emergency department visits, hospital admissions,
      hospitalized days, missed work or school days and missed days of leisure time.
      There were also statistically significant improvements in all but one SF-36
      domain. These improvements were comparable across all geographical sites and
      physical settings. CONCLUSIONS: Standardized asthma education appears to be
      effective when administered in a variety of practice settings, and may be
      associated with significant improvements in patient outcomes. The significant
      decline in health care utilization implies that substantial health care savings
      may occur as a result of the implementation of standardized asthma education
      programs.

PMID- 15254612
TI  - Screening for common respiratory diseases among Israeli adolescents.
AB  - BACKGROUND: Respiratory diseases are responsible for a significant proportion of
      serious morbidity among adolescents. There are few reports on the prevalence of
      common respiratory disorders in this population. The previous studies focused on
      specific diseases and screened relatively small samples. OBJECTIVE: To define the
      prevalence of different common respiratory disorders among 17-year-old Israeli
      conscripts. DESIGN: All 17-year-old Israeli nationals are obliged by law to
      appear at the Israel Defense Forces recruiting office for medical examination.
      Respiratory disease specialists evaluated and classified nominees with suspected
      respiratory disorders. RESULTS: A high prevalence of respiratory morbidity was
      found among 94,805 17-year-old conscripts (61.5% male, 39.5% female). The most
      prevalent diagnosis was asthma (in 8% of male and 6.8% of female subjects). Fifty
      five per cent of the asthma patients suffered from moderate to severe disease.
      The prevalence of chronic obstructive pulmonary disease was 0.03% for the male
      and 0.01% for the female subjects. A difference in morbidity patterns between
      male and female adolescents was noted, particularly in the prevalence of chest
      deformation and spontaneous pneumothorax. CONCLUSIONS: The most prevalent
      respiratory disorder among 17-year-old Israeli conscripts was asthma. One-half of
      the asthma patients in this study suffered from moderate to severe disease. The
      prevalence of other respiratory disorders was much lower.

PMID- 15254613
TI  - The use of clinical practice guidelines for community-acquired pneumonia in
      hospitals in Atlantic Canada.
AB  - BACKGROUND: Clinical practice guidelines (CPGs) have been shown to improve the
      care of patients presenting to hospital with community-acquired pneumonia (CAP)
      and are considered the 'standard of care'. The extent of adoption of CPGs in
      Canada is unclear. OBJECTIVE: To determine the use of CPGs by hospitals in
      Atlantic Canada (Newfoundland, Nova Scotia, New Brunswick, Prince Edward Island).
      METHODS: Telephone survey of all hospitals listed in the Canadian Medical
      Directory as being situated in Atlantic Canada. Hospitals were included if they
      had all three of the following: an emergency department, x-ray facilities and
      acute care inpatient beds. RESULTS: Of 143 hospitals, 93 were included for
      analysis. Of these, 41 (44.1%) used CAP CPGs. Hospitals were less likely to be
      using CAP CPGs if they were smaller, rural or community hospitals, or if they did
      not have an intensive care unit. Of the four provinces, New Brunswick had the
      most hospitals using CAP CPGs (73.1%), while Newfoundland had the least (17.2%).
      CONCLUSIONS: Although larger teaching hospitals are using CAP CPGs, the degree of
      adoption of CPGs in smaller hospitals in Atlantic Canada is low. Efforts to
      produce standard CPGs that can be adapted to different sites, as well as
      implementation strategies, are indicated.

PMID- 15254614
TI  - Endobronchial electrocautery and argon plasma coagulation: a practical approach.
AB  - The present review covers the technical and practical aspects of endobronchial
      electrocautery, including argon plasma coagulation, which have great potential
      for widespread use by pulmonologists around the world. The various electrocautery
      modes, power settings and electrode probes are described in detail, and the
      authors' clinical and technical approach is demonstrated with a narrative
      description and brief case presentations. Malignant airway obstruction,
      hemoptysis, web-like stenosis, stent related granulation tissue and early lung
      carcinomas are the most common indications for treatment. Advantages of
      electrocautery, such as low cost, rapid effect, safety and ease of use, are
      contrasted to other endobronchial therapeutic modalities. Published experience
      with electrocautery is reviewed.

PMID- 15254615
TI  - High dose intravenous methylprednisolone in the treatment of severe acute
      respiratory syndrome.
AB  - The case of a 72-year-old woman with probable severe acute respiratory syndrome
      is reported. While on treatment with ribavirin and antibiotics (for community
      acquired pneumonia), the patient continued to have progressive clinical
      deterioration and chest radiographic evidence of respiratory deterioration. Pulse
      dose intravenous corticosteroids were used in an unsuccessful attempt to treat
      the inflammatory component of this respiratory illness.

PMID- 15254616
TI  - The sulfinic acid switch in proteins.
AB  - Recent studies on the redox behaviour of cysteine residues in peptides and
      proteins have dramatically changed our perspective of the amino acid's role in
      biocatalysis, intracellular redox sensing and cell signalling. Cysteine sulfinic
      acid formation in proteins, for example, has long been viewed as an irreversible
      'overoxidation' process that might lead to loss of activity, especially under
      conditions of oxidative stress. Within the last year, several research groups
      have independently shown that sulfinic acids can be reduced to thiols in vivo. An
      enzyme with sulfinic acid reductase activity, called sulfiredoxin, has been
      isolated from yeast and a gene encoding a human analogue has been identified in
      the human genome. Reversibility of sulfinic acid formation opens the door to a
      range of yet unexplored redox cycles, cell signalling processes and reduction
      mechanisms. These cysteine-based redox processes will be of enormous interest to
      chemists, biochemists, biologists and the medical community alike.

PMID- 15254617
TI  - RNAi: running interference for the cell.
AB  - RNA interference or RNAi is a recently characterized mechanism of eukaryotic gene
      regulation in which a short sequence of double-stranded RNA (dsRNA) specifically
      down-regulates expression of the associated gene. Preliminary characterization of
      this phenomenon has revealed a set of inter-related cellular pathways which
      appear to represent both a response to foreign RNA and a mechanism of endogenous
      gene regulation. Introduction of dsRNA into cells by a variety of means,
      including transfection of synthetic RNA duplexes, triggers the RNAi response
      resulting in specific suppression of target gene expression. Recent efforts on a
      genome wide scale have involved application of RNAi as an important new tool in
      cell biology to elucidate gene function in living cells.

PMID- 15254618
TI  - New Rebek imide-type receptors for adenine featuring acetylene-linked pi-stacking
      platforms.
AB  - Rebek imide-type molecular clefts with pi-stacking platforms attached to the
      imide scaffold by an acetylene linker have been prepared by Sonogashira cross
      coupling. In the solid state, a novel dimerisation mode for this class of imide
      receptors was found by crystal structure analysis, whereas efficient 1 : 1
      complexation with 9-ethyladenine was observed in CDCl3 solution.

PMID- 15254619
TI  - A new environment-sensitive fluorescent amino acid for Fmoc-based solid phase
      peptide synthesis.
AB  - A new 4-(N,N-dimethylamino) phthalimide-based environment-sensitive fluorescent
      building block for solid phase peptide synthesis, has been synthesized and
      incorporated into peptides. Peptides incorporating this residue show great
      potential for biological applications in sensing protein/protein interactions.

PMID- 15254620
TI  - The first series of chiral 2,2':6',2''-terpyridine tri-N-oxide ligands for Lewis
      base-catalyzed asymmetric allylation of aldehydes.
AB  - The first series of chiral 2,2':6',2''-terpyridine tri-N-oxide ligands have been
      developed; They were showed to be active Lewis base-catalysts for asymmetric
      allylation of aldehydes using allyltrichlorosilane with optimal results at 0
      degrees C for electron-deficient aromatic aldehydes (yields up to 97% and
      enantioselectivities up to 86% ee).

PMID- 15254621
TI  - 15NH4+ ion movement inside d(G4T4G4)2 G-quadruplex is accelerated in the presence
      of smaller Na+ ions.
AB  - 2D NMR studies demonstrate that the residence lifetime of 15NH4+ ions within the
      bimolecular G-quadruplex adopted by d(G4T4G4) is reduced from 270 ms in the
      presence of ammonium ions alone to 36 ms in the presence of Na+ ions.

PMID- 15254622
TI  - Synthesis of alpha-iminoimidates by palladium catalysed double isonitrile
      insertion.
AB  - Palladium catalysed selective double insertion of isonitriles into aryl bromides
      with trapping by sodium alkoxides provides an efficient 4-component synthesis of
      unusual alpha-iminoimidates.

PMID- 15254623
TI  - The first aminoacylase-catalyzed enantioselective synthesis of aromatic beta
      amino acids.
AB  - The first aminoacylase-catalyzed enantioselective synthesis of aromatic beta
      amino acids is reported. The presence of an N-chloroacetyl group as acyl group in
      the substrate as well as the use of porcine kidney acylase I as a suitable enzyme
      component are prerequisites for this resolution process whereby optically active
      beta-amino acids are formed with high enantioselectivities of >98% ee.

PMID- 15254624
TI  - Novel polymer-supported coupling/dehydrating reagents for use in organic
      synthesis.
AB  - Two novel dehydrating reagents and, based on a phosphonium anhydride and an
      oxyphosphonium triflate respectively, were prepared by reaction of the
      corresponding polymer-supported phosphine oxides with triflic anhydride. Reagent,
      based on the novel phosphorus heterocycle 1,1,3,3-tetraphenyl-2-oxa-1,3
      diphospholanium bis(trifluoromethanesulfonate), was found to be a useful reagent
      for ester and amide formation. A wide range of coupling/dehydration-type
      reactions, such as ester, amide, anhydride, peptide, ether and nitrile formation,
      were performed in high yield using the more readily prepared polymer-supported
      triphenylphosphine ditriflate, which was easily recovered and re-used several
      times without loss of efficiency. With primary alcohols, both reagents and
      provide an alternative to the Mitsunobu reaction, where the use of
      azodicarboxylates and chromatography to remove the phosphine oxide by-product can
      be avoided. The use of 4-dimethylaminopyridine allowed the esterification of
      secondary alcohols with to proceed in high yield but with retention of
      configuration.

PMID- 15254625
TI  - Enzymatic synthesis of complex glycosaminotrioses and study of their molecular
      recognition by hevein domains.
AB  - Hevein, a protein found in Hevea brasiliensis, has a CRD domain, which is known
      to bind chitin and GlcNAc-containing oligosaccharides. By using NMR and molecular
      modeling as major tools we have demonstrated that trisaccharides containing
      GalNAc and ManNAc residues are also recognized by hevein domains. Thus far
      unknown trisaccharides GlcNAcbeta(1-->4)GlcNAcbeta(1-->4)ManNAc (1) and
      GalNAcbeta(1-->4)GlcNAcbeta(1-->4)ManNAc (2) were synthesized with the use of
      beta-N-acetylhexosaminidase from Aspergillus oryzae. This method is based on the
      rather unique phenomenon that some fungal beta-N-acetylhexosaminidases cannot
      hydrolyze disaccharide GlcNAcbeta(1-->4)ManNAc (5) contrary to chitobiose
      GlcNAcbeta(1-->4)GlcNAc (4) that is cleaved and, therefore, cannot be used as an
      acceptor for further transglycosylation. Both trisaccharides 1 and 2 were
      prepared by transglycosylation from disaccharidic acceptor in good yields ranging
      from 35% to 40%. Our observations strongly indicate that the present nature of
      the modifications of chitotriose (GlcNAcbeta(1-->lcNAcbeta(1-->4)GlcNAc, 3) at
      either the non-reducing end (GalNAc instead of GlcNAc) or at the reducing end
      (ManNAc instead of GlcNAc) do not modify the mode of binding of the trisaccharide
      to hevein. The association constant values indicate that chitotriose (3) binding
      is better than that of 1 and 2, and that the binding of (with ManNAc at the
      reducing end) is favored with respect to that of 2 (with ManNAc at the reducing
      end with a non-reducing GalNAc moiety).

PMID- 15254626
TI  - Preparation of enantiopure biimidazoline ligands and their use in asymmetric
      catalysis.
AB  - A convenient new method for the preparation of 2,2'-biimidazolines is reported.
      Amino alcohols were reacted with dimethyl oxalate, and the product hydroxy amides
      converted into chloroamides by reaction with thionyl chloride. Treatment with
      PCl5, followed by diamines (ethanediamine, propane-1,3-diamine, 2,2
      dimethylpropane-1,3-diamine) furnished a series of enantiopure tricyclic
      biimidazolines. Complexes of two of the ligands with PdCl2 were prepared and
      their X-ray crystal structures were determined. The biimidazolines were tested as
      ligands for asymmetric Pd-catalysed allylations. Moderate enantioselectivity (up
      to 80% ee) was found for the reaction of dimethyl malonate with diphenylallyl
      acetate, with the 5,7,5 fused tricyclic systems outperforming the 5,6,5
      analogues. The corresponding reaction of pentenyl acetate gave lower
      enantioselectivity (44-57% ee), and proved very sensitive to the donor strength
      of the ligands, the stronger donors giving lower yields. The results provide a
      further demonstration of the value of the 'tunability' of imidazoline ligands.

PMID- 15254627
TI  - Studies towards the total synthesis of batzelladine A.
AB  - Application of a diastereoselective three-component coupling to the bicyclic core
      of the batzelladine alkaloids is described. The synthesis features the
      elaboration of glutamic acid by use of Eschenmoser sulfide contraction. An
      earlier approach is also included, which shows some limitations of dithiane
      chemistry when applied to the particular compounds required for this target.

PMID- 15254628
TI  - Squalene-hopene cyclase: insight into the role of the methyl group on the
      squalene backbone upon the polycyclization cascade. Enzymatic cyclization
      products of squalene analogs lacking a 26-methyl group and possessing a methyl
      group at C7 or C11.
AB  - To provide deep insight into the polycyclization reaction of squalene, some
      analogs were synthesized and incubated with the cell-free homogenates of the
      recombinant Escherichia coli encoding the wild-type squalene cyclase. The
      presence of C6-Me leads to an efficient polycyclization cascade. Substitution of
      the C14-H and the C18-H with a methyl group halted the polycylization reaction at
      the tricyclic ring stage having a 6/6/6-fused ring system and the tetracycle with
      a 6/6/6/6-fused ring, respectively, both of which were produced according to a
      Markovnikov closure. Replacement of the C7-H and the C11-H with a methyl group
      led to no cyclization. These results, in conjunction with our previous reports,
      indicated that the methyl positions are important for bringing to completion of
      the normal polycylization reaction and further demonstrated that the precise
      steric bulk size at the methyl positions of squalene is critical to the correct
      folding and the strong binding of the substrate to the squalene cyclase.

PMID- 15254629
TI  - O-Protected 3-hydroxy-oxazolidin-2,4-diones: novel precursors in the synthesis of
      alpha-hydroxyhydroxamic acids.
AB  - O-Protected 3-hydroxyoxazolidin-2,4-diones have been prepared in a novel one-pot
      reaction by subsequent treatment of cyanohydrins with 1,1'-carbonyldiimidazole
      and O-protected hydroxylamines followed by acidic hydrolysis of the intermediate
      4-imino-oxazolidin-2-ones. Decarbonylation of O-protected 3-hydroxyoxazolidin-2,4
      diones by catalytic amounts of sodium methoxide, lithium hydroxide, sodium
      carbonate and caesium carbonate in methanol afforded O-protected alpha
      hydroxyhydroxamic acids in excellent yields. Their deprotection provided a series
      of novel alpha-hydroxyhydroxamic acids.

PMID- 15254630
TI  - Synthesis and biological evaluation of new cross-conjugated dienone marine
      prostanoid analogues.
AB  - The synthesis of a series of brominated cross-conjugated dienones, marine
      prostanoid analogues, was considered using two cyclopentannelation processes,
      from enamine (by a domino 3-aza Claisen/Mannich reaction) and from dioxolane
      ester alkylation followed by intramolecular Wittig reaction. All the compounds
      synthesized featured the same cross-conjugated dienone system, with a vicinal syn
      or anti diol on the omega-chain. The replacement of the omega-side-chain of the
      natural prostanoids with a 1-hydroxyphenyl-butyl moiety gave new prostanoids (32
      34) with good cytotoxicities. In a second series of products, the possibility of
      a shorter alpha-side-chain bearing a simple phenyl ester was investigated. The
      results indicated a dramatic increase in the cytotoxicity (39, 40, 43, 44).
      Finally, in a third series, the omega-1-hydroxyphenyl-butyl was replaced by a 1
      hydroxymethyloxybenzyl chain. These simpler compounds (45, 46, 47, 48, 60) are
      still highly cytotoxic, in the medium range of 60 nM, close to the value of
      natural punaglandins.

PMID- 15254631
TI  - Rate and product studies with dimethyl phosphorochloridate and
      phosphorochloridothionate under solvolytic conditions.
AB  - The specific rates of solvolysis of dimethyl phosphorochloridate and of dimethyl
      phosphorochloridothionate are very well correlated using the extended Grunwald
      Winstein equation, with incorporation of the NT solvent nucleophilicity scale and
      the YCl solvent ionizing power scale. The sensitivity parameters (l and m) are
      similar to each other and also similar to previously recorded values for
      solvolyses of arenesulfonyl chlorides, which were proposed to follow a concerted
      displacement mechanism. For solvolyses in aqueous ethanol or aqueous methanol the
      product selectivities (S) are close to unity. For solvolyses in aqueous 2,2,2
      trifluoroethanol, the values are too small to accurately measure, showing a very
      large preference for product formation involving nucleophilic attack by the water
      component. It is concluded that the chloride and chloridothionate solvolyses, in
      common with the solvolyses of arenesulfonyl chlorides, follow a concerted
      displacement mechanism.

PMID- 15254632
TI  - Mimicking enzymatic transaminations: attempts to understand and develop a
      catalytic asymmetric approach to chiral alpha-amino acids.
AB  - Attempts are made to build a bridge between asymmetric catalysis and enzymatic
      reactions by mechanistic investigations and the development of a catalytic and
      enantioselective approach to amination of alpha-keto esters by primary amines
      catalyzed by chiral Lewis acids as a model for transamination enzymes. Different
      Lewis acids can catalyze the half-transamination of alpha-keto esters using
      primary amine nitrogen sources such as pyridoxamine and 4-picolylamine. The
      mechanistic studies of the Lewis-acid catalyzed half-transamination using
      deuterium-labelled compounds show the incorporation of deuterium atoms in several
      positions of the alpha-amino acid derivative, indicating that the enol of the
      alpha-keto ester plays an important role along the reaction path. The catalytic
      enantioselective reactions are dependent on the pKa-value of the solvent since
      enantioselectivities were only obtained in solvents with high pKa-values relative
      to methanol. However, stronger acidic conditions generally gave better yields,
      but poor enantioselectivities. A series of chiral Lewis acids were screened as
      catalysts for the enantioselective half-transamination reactions and moderate
      yields and enantioselectivities of up to 46% ee were obtained.

PMID- 15254633
TI  - A chemoenzymatic total synthesis of the phytotoxic undecenolide (-)-cladospolide
      A.
AB  - An eleven-step synthesis of the title compound (1) from biocatalytically-derived
      and enantiomerically pure 'building blocks' alcohol (R)-(-)-9 and ester 13 is
      described. Attempts to construct the twelve-membered lactone ring of cladospolide
      A in a direct manner by using a ring-closing metathesis (RCM) reaction failed.
      However, a ten-membered lactone 19, could be constructed by such means and this
      was then subject to a two-carbon homologation sequence involving, inter alia,
      Wadsworth-Horner-Emmons and Yamaguchi lactonisation reactions in the closing
      stages of the synthesis. The impact of substituent stereochemistries and
      protecting groups on the RCM reaction leading to various ten-membered lactones is
      also described.

PMID- 15254634
TI  - New approaches to the industrial synthesis of HIV protease inhibitors.
AB  - Efficient and industrially applicable synthetic processes for precursors of HIV
      protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a
      novel and economical method for the preparation of a key intermediate, (3S)
      hydroxytetrahydrofuran, from l-malic acid. Three new approaches to the assembly
      of Amprenavir are also discussed. Of these, a synthetic route in which an (S)
      tetrahydrofuranyloxy carbonyl is attached to l-phenylalanine appears to be the
      most promising manufacturing process, in that it offers satisfactory
      stereoselectivity in fewer steps.

PMID- 15254635
TI  - Expected and unexpected results from combined beta-hairpin design elements.
AB  - A model beta-hairpin dodecapeptide [EFGWVpGKWTIK] was designed by including a
      favorable D-ProGly Type II' beta-turn sequence and a Trp-zip interaction, while
      also incorporating a beta-strand unfavorable glycine residue in the N-terminal
      strand. This peptide is highly folded and monomeric in aqueous solution as
      determined by combined analysis with circular dichroism and 1H NMR spectroscopy.
      A peptide representing the folded conformation of the model beta-hairpin
      [cyclic(EFGWVpGKWTIKpG)] and a linear peptide representing the unfolded
      conformation [EFGWVPGKWTIK] yield unexpected relative deviations between the CD
      and 1H NMR spectroscopic results that are attributed to variations in the packing
      interactions of the aromatic side chains. Mutational analysis of the model beta
      hairpin indicates that the Trp-zip interaction favors folding and stability
      relative to an alternate hydrophobic cluster between Trp and Tyr residues
      [EFGYVpGKWTIK]. The significance of select diagonal interactions in the model
      beta-hairpin was tested by rearranging the cross-strand hydrophobic interactions
      to provide a folded peptide [EWFGIpGKTYWK] displaying evidence of an unusual
      backbone conformation at the hydrophobic cluster. This unusual conformation does
      not appear to be a result of the glycine residue in the beta-strand, as
      replacement with a serine results in a peptide [EWFSIpGKTYWK] with a similar and
      seemingly characteristic CD spectrum. However, an alternate arrangement of
      hydrophobic residues with a Trp-zip interaction in a similar position to the
      parent beta-hairpin [EGFWVpGKWITK] results in a folded beta-hairpin conformation.
      The differences between side chain packing of these peptides precludes meaningful
      thermodynamic analysis and illustrates the caution necessary when interpreting
      beta-hairpin folding thermodynamics that are driven, at least in part, by
      aromatic cross strand interactions.

PMID- 15254636
TI  - Rate constants for hydrogen abstraction from alkoxides by a perfluoroalkyl
      radical. An oxyanion accelerated process.
AB  - A combination of laser flash photolysis and competitive kinetic methods has been
      used to measure the absolute bimolecular rate constants for hydrogen atom
      abstraction in water from a series of fluorinated alkoxides and aldehyde hydrates
      by the perfluoroalkyl radical, *CF2CF2OCF2CF2SO3- Na+. The bimolecular rate
      constants observed for the beta-fluorinated alkoxides were in the 10(5) M(-1) s(
      1) range, such rates representing enhancements (relative to the respective
      alcohols) of between 100 and almost 1000-fold, depending on the reactivity of the
      alkoxide. Likewise, the monobasic sodium salts of chloral and fluoral hydrate
      exhibit similar rate enhancements, relative to their respective hydrates.

PMID- 15254637
TI  - Large primary kinetic isotope effects in the abstraction of hydrogen from organic
      compounds by a fluorinated radical in water.
AB  - Isotope effects have been measured for the abstraction of hydrogen from a series
      of organic substrates by the perfluoro radical, Na+ -O3SCF2CF2OCF2CF2*, in water.
      Both primary and secondary deuterium isotope effects were measured, with the
      primary isotope effects ranging in value from 4.5 for isopropanol to 19.6 for
      acetic acid. The values for the alpha- and beta-secondary deuterium isotope
      effects were 1.06 and 1.035, respectively. It was concluded that tunneling
      contributes significantly to the production of the observed, large primary
      kinetic isotope effects in these C-H abstraction reactions.

PMID- 15254638
TI  - Total synthesis and biological evaluation of +-kalkitoxin, a cytotoxic metabolite
      of the cyanobacterium Lyngbya majuscula.
AB  - +-Kalkitoxin, a metabolite of the marine cyanobacterium Lyngbya majuscula, was
      synthesized from (R)-2-methylbutyric acid, (R)-cysteine, and (3S, 4S, 6S)-3,4,6
      trimethyl-8-(methylamino)octanoic acid. A key step in the synthesis was
      installation of the anti,anti methyl stereotriad by means of a tandem asymmetric
      conjugate addition of an organocopper species to an alpha,beta-unsaturated N-acyl
      oxazolidin-2-one followed in situ by alpha-methylation of the resultant enolate.
      The thiazoline portion of kalkitoxin was assembled by titanium tetrachloride
      catalyzed cyclization of a vinyl substituted amido thiol.

PMID- 15254639
TI  - The synthesis and properties of oligoribonucleotide-spermine conjugates.
AB  - Polyamines stabilise nucleic acids against chemical and enzymatic degradation,
      facilitate the formation of secondary and tertiary structures and enhance
      cellular uptake. Therefore methods for the syntheses of polyamine-nucleic acid
      conjugates are of interest. A route for the syntheses of RNA-spermine conjugates
      has been developed. The polyamine was introduced to the C-5 position of uridine
      via an ethyl tether and the molecule elaborated into a synthon suitable for
      oligoribonucleotide assembly. The resultant oligomers were components of the
      hairpin ribozyme. Characterisation of the spermine-conjugated catalytic RNA
      revealed that attachment of the polyamine was well tolerated in three of four
      positions, namely U41, U37 and U34, suggesting that conjugation to C-5 brings
      about minimal structural perturbation.

PMID- 15254640
TI  - Synthesis and cholera toxin binding properties of multivalent GM1 mimics.
AB  - Dendrimers based on the 3,5-di-(2-aminoethoxy)-benzoic acid branching unit were
      used to attach multiple copies of a GM1 mimic for inhibition of cholera toxin
      binding. Systems up to octavalent were synthesized along with relevant reference
      compounds that contained in one case the ligand in a monovalent format and in
      another case the scaffold but not the ligand. Using a surface plasmon resonance
      inhibition assay the prepared inhibitors showed good inhibition. While the
      monovalent GM1 mimic showed the expected inhibition in the 200 microM range the
      multivalent scaffolds led to increased binding. The tetravalent compound was
      shown to be 440-fold more potent than its monovalent counterpart. The octavalent
      analog, however, was the most potent compound as determined using an ELISA assay.

PMID- 15254641
TI  - Stereochemical variations on the colchicine motif. Peracid oxidation of
      thiocolchicone. Synthesis, conformation and inhibition of microtubule assembly.
AB  - When 7-oxodesacetamidothiocolchicine (1) was treated with various peroxides in
      order to afford a Baeyer-Villiger rearrangement, a complex mixture of products
      was formed, which included the sulfoxide, (2) and sulfone, (3). When peracetic
      acid was used two additional products were formed; a C-ring lactone (4) and a
      ring-contracted allocolchicine derivative (5). The sulfoxide (2) was semi
      preparatively resolved into enantiomers by chromatography on microcrystalline
      triacetylcellulose. Rotational barriers around the A-C pivot bond of, and were
      determined by dynamic 1H NMR analysis. The compounds, and exhibit moderate
      inhibition of tubulin polymerization, according to in vitro turbidity studies,
      whereas was inactive.

PMID- 15254644
TI  - Robots in the operating room--the history.
AB  - The history of robotics can be traced back to the automata of ancient Greece, but
      it has only been within the last 50 years that machines have been made to mimic
      human actions in order to perform labor rather than to entertain and amuse.
      Furthermore, it has been only within the last 20 years that robotic technology
      has been applied to the practice of surgery. The goal of this technology has not
      been to replace the surgeon, but rather to enhance his or her performance with
      highly advanced tools. We present a brief history of some of the key points in
      the development of surgical robotics and discuss the advantages and disadvantages
      of the various US Food and Drug Administration-approved robotic surgical systems
      and surgical robots in general.

PMID- 15254642
TI  - Peribysins A-D, potent cell-adhesion inhibitors from a sea hare-derived culture
      of Periconia species.
AB  - Peribysins A-D 1-4, including a new type of furanofuran, have been isolated from
      a strain of Periconia byssoides originally separated from the sea hare Aplysia
      kurodai, and their relative stereostructures have been elucidated on the basis of
      NMR spectral analyses. All these metabolites potently inhibited the adhesion of
      human-leukemia HL-60 cells to HUVEC. The activity of compound 4, exhibiting the
      most potent inhibitory activity, was 380 times as potent as herbimycin A
      (standard).

PMID- 15254645
TI  - Robot-assisted cardiac surgery.
AB  - The use of robotics is evolving in cardiac surgery. Robots allow minimally
      invasive techniques to be applied to ischemic heart and valve disease. Notably,
      this frees the patient from sternotomy, allowing a quick recovery while
      preserving the most critical aspects of the surgical procedure. The increasing
      use of stents for revascularization is significant. For best results to the
      patient, the graft of the left internal mammary artery (LIMA) to the left
      anterior descending artery (LAD) is a mainstay of symptom-free survival. Stenting
      and robotic LIMA-to-LAD grafting in a one-staged or two-staged approach may be an
      attractive combined specialty treatment. This would offer best practices to the
      patient, along with the best technologies available. In this chapter, the most
      common techniques in cardiac robotic surgery are outlined. Procedural steps are
      described, and their expanding indications for use discussed. Additionally, a
      focus on combining technologies for new treatments is considered.

PMID- 15254646
TI  - Robot-assisted urologic procedures.
AB  - Surgical robotics, the result of the combined efforts of engineers, computer
      scientists, entrepreneurs, and surgeons, has enabled the surgeon to execute
      precise technical maneuvers while seated at a remote console. The capability to
      perform sophisticated surgical operations by means of a robot is today's reality.
      The combination of laparoscopy and robotics has the potential to enhance
      operative performance and the outcomes of laparoscopy, and expand the clinical
      application of laparoscopy while reducing patient morbidity. In this article, we
      review initial pioneering and laboratory research, early clinical investigations,
      and current clinical applications of robotics in urologic surgery.

PMID- 15254647
TI  - Robot-assisted orthopedic surgery.
AB  - The main advantages of robot-assisted orthopedic surgery over conventional
      orthopedic techniques are improved accuracy and precision in the preparation of
      bone surfaces, more reliable and reproducible outcomes, and greater spatial
      accuracy. Orthopedic surgery is ideally suited for the application of robotic
      systems. The ability to isolate and rigidly fix bones in known positions allows
      robotic devices to be securely fixed to the bone. As such, the bone is treated as
      a fixed object, simplifying the computer control of the robotic system.
      Commercially available robotic systems can be categorized as either passive or
      active devices, or can be categorized as positioning or milling/cutting devices.
      Computer assisted orthopedic surgery is a related area of technological
      development in orthopedics; however, robot-assisted orthopedic surgery can
      achieve levels of accuracy, precision, and safety not capable with computer
      assisted orthopedic surgery. Applications of robot-assisted orthopedic surgery
      currently under investigation include total hip and knee replacement, tunnel
      placement for reconstruction of knee ligaments, and trauma and spinal procedures.
      Several short-term studies demonstrate the feasibility of robotic applications in
      orthopedics, however, there are no published long-term data defining the efficacy
      of robot-assisted orthopedic surgery. Issues of cost, training, and safety must
      be addressed before robot-assisted orthopedic surgery becomes widely available.
      Robot-assisted orthopedic surgery is still very much in its infancy but it has
      the potential to transform the way orthopedic procedures are done in the future.

PMID- 15254648
TI  - Robot-assisted neurosurgery.
AB  - Technological advances in the modern operating room have pushed neurosurgeons to
      the limits of their dexterity and stamina. Motion scalers and tremor filters on
      robots permit unprecedented precision of tool manipulation, upgrading the human
      hand, and closing the deftness deficit. The evolution of neurosurgical robots
      from stereotactic systems to hybrid systems capable of both stereotaxy and
      microsurgery is examined. The future of robot-assisted neurosurgery, including
      expanded tool sets and the prospect of semi-autonomous surgery, is discussed.

PMID- 15254649
TI  - Robot-assisted general surgery.
AB  - With the initiation of laparoscopic techniques in general surgery, we have seen a
      significant expansion of minimally invasive techniques in the last 16 years. More
      recently, robotic-assisted laparoscopy has moved into the general surgeon's
      armamentarium to address some of the shortcomings of laparoscopic surgery. AESOP
      (Computer Motion, Goleta, CA) addressed the issue of visualization as a robotic
      camera holder. With the introduction of the ZEUS robotic surgical system
      (Computer Motion), the ability to remotely operate laparoscopic instruments
      became a reality. US Food and Drug Administration approval in July 2000 of the da
      Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) further defined
      the ability of a robotic-assist device to address limitations in laparoscopy.
      This includes a significant improvement in instrument dexterity, dampening of
      natural hand tremors, three-dimensional visualization, ergonomics, and camera
      stability. As experience with robotic technology increased and its applications
      to advanced laparoscopic procedures have become more understood, more procedures
      have been performed with robotic assistance. Numerous studies have shown
      equivalent or improved patient outcomes when robotic-assist devices are used.
      Initially, robotic-assisted laparoscopic cholecystectomy was deemed safe, and now
      robotics has been shown to be safe in foregut procedures, including Nissen
      fundoplication, Heller myotomy, gastric banding procedures, and Roux-en-Y gastric
      bypass. These techniques have been extrapolated to solid-organ procedures
      (splenectomy, adrenalectomy, and pancreatic surgery) as well as robotic-assisted
      laparoscopic colectomy. In this chapter, we review the evolution of robotic
      technology and its applications in general surgical procedures.

PMID- 15254650
TI  - Image-guided robotic surgery.
AB  - Medical image processing leads to an improvement in patient care by guiding the
      surgical gesture. Three-dimensional models of patients that are generated from
      computed tomographic scans or magnetic resonance imaging allow improved surgical
      planning and surgical simulation that offers the opportunity for a surgeon to
      train the surgical gesture before performing it for real. These two preoperative
      steps can be used intra-operatively because of the development of augmented
      reality, which consists of superimposing the preoperative three-dimensional model
      of the patient onto the real intraoperative view. Augmented reality provides the
      surgeon with a view of the patient in transparency and can also guide the
      surgeon, thanks to the real-time tracking of surgical tools during the procedure.
      When adapted to robotic surgery, this tool tracking enables visual serving with
      the ability to automatically position and control surgical robotic arms in three
      dimensions. It is also now possible to filter physiologic movements such as
      breathing or the heart beat. In the future, by combining augmented reality and
      robotics, these image-guided robotic systems will enable automation of the
      surgical procedure, which will be the next revolution in surgery.

PMID- 15254651
TI  - Robot-assisted remote telepresence surgery.
AB  - A potential application of robotic surgical systems is to act as the hands and
      eyes of a surgeon operating from a considerable distance, enabling the surgeon to
      offer a variety of surgical services through gaining true telepresence by the
      interface of the telecommunication link and a surgical robotic system. The
      limited use of robot-assisted remote telepresence surgery to date has
      demonstrated not only that this is technologically feasible and safe but also
      that the patients are willing to accept its limitations when it is used in an
      environment where significant value from its use is realized. This chapter will
      discuss some of the lessons learned, the potential future applications, and the
      necessary next steps for its safe and widespread adoption.

PMID- 15254652
TI  - Future trends in the design and application of surgical robots.
AB  - Beyond current laparoscopic surgery is the emergence of robotic surgery. The
      power of this type of surgery is converting both vision and hand motions into
      electronic signals (video and telemanipulation), which completes the transition
      of surgery from the Industrial Age to the Information Age. Other advances include
      replacing scrub and circulation nurses with robots, miniaturization, biosurgery,
      "intelligent" instruments, and energy-directed rather than mechanical surgical
      tools. These modalities will supplement-but not totally replace-current forms of
      surgery such as open conventional, minimally invasive, endoluminal, and
      interventional.

PMID- 15254653
TI  - NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions
      as likely mechanisms behind the acetaminophen- and NSAID-prevention of the
      ovarian cancer.
AB  - Recent epidemiological studies indicated risk reductions in ovarian cancer with
      consumption of acetaminophen or non-steroid anti-inflammatory drugs. Until now,
      there is not a systematic analysis, why these agents may reduce risk of ovarian
      cancer, as it has been performed to explain aspirin-reduction of colon cancer
      risk. This review tries to explain molecular mechanisms pertinent to
      acetaminophen- and NSAID-reduction of ovarian cancer. It is proposed that the
      major mechanism by these anti-inflammatory agents is a shared pathway dependent
      on the suppression of NF-kappaB activity, which may subsequently decrease
      transcription of growth factors, chemokines and proteases such as COX-2, VEGF, IL
      8/CXCL8, MCP-1/CCL-2, MIP1alpha/CCL-3, tPA and uPA, which are shown to be
      elevated in ovarian carcinoma, and which play diverse roles such as inducing
      angiogenesis, invasion, autocrine growth loops and resistance to apoptosis.
      Besides these, specific mechanisms of action can be attributed to acetaminophen
      reduction of ovarian cancer risk via I. Induction of specific reproductive
      atrophy due its sex-steroid resembling phenolic ring; II. Reduction of
      glutathione pools due to its NAPQI metabolite, which may play an important role
      for sterilizing pre-malignant ovarian lesions, since they are shown to lack
      proper levels of glutathione; III. Inhibition of tautomerization activity of MIF
      (macrophage migration inhibitory factor), which is shown to be released from
      ovarian cancer, and which is necessary for proper ovulation; IV. Inhibition of
      cytokine-induced and endothelia-origined cyclooxygenases. Except the
      chemosensitization studies, acetaminophen and NSAIDs should be investigated in
      animal models to test likely benefits in ovarian cancer, since most of their
      activity may origin from intervening with the cancer growth-stimulating
      inflammatory stimuli, rather than with the direct cellular toxicity.

PMID- 15254654
TI  - Increasing occurrence of urological cancers in Slovakia.
AB  - Similarly as in other developed countries of the world cancers of the upper and
      lower urinary tract are increasing also in Slovakia. Of greater importance are
      urological cancers in men participating recently worldwide with 17% on all newly
      diagnosed cancers. In women only 3% of all incident cases occur in urological
      sites. Data on incidence of urological cancers in the period 1968-1999 were
      derived from the National Cancer Registry, while those of mortality from the
      Statistical Office of the Slovak Republic. World standard population was used for
      the age-adjustment of both indicators. Temporal trends were evaluated using
      Poisson regression and computation of mean annual percent changes (MACP).
      Substantial and nearly parallel increase of incidence and of mortality has been
      observed for prostate cancer. Despite dramatic increase of testicular cancers
      incidence, corresponding mortality rates remained stable with the tendency to
      decrease recently. Incidence and mortality rates of urinary bladder cancer in men
      showed tendency to peaking while in women incidence increased and mortality
      showed tendency to stabilization. Incidence rates of kidney cancers increased in
      both sexes during the whole period, followed by slow increase of mortality at
      substantially lower levels. With the exception of mortality from testicular
      cancer all analyzed trends were statistically significant. In conclusion, only in
      the case of testicular cancer important reduction of mortality has been obtained
      despite dramatic increase of incidence. Reduction of smoking and improvement of
      industrial hygiene may influence the development of bladder cancer incidence and
      mortality. Limited resources for establishment of a concise cancer control
      program in this country do not allow to slow down in the near future the increase
      of incidence and mortality of prostate and kidneys cancers in Slovakia.

PMID- 15254655
TI  - Lung cancer risk among Czech tin and uranium miners--comparison of lifetime
      detriment.
AB  - First epidemiological evidence of lung cancer risk from exposure to radon was
      based on studies of uranium miners. The risk in other mines was reported later.
      The cohort study among 2466 Czech tin miners was conducted in order to estimate
      the size of the risk and to compare it to that in uranium mines. Based on 205
      lung cancers, the estimate of excess relative risk per unit exposure in the
      simple linear model 0.011 is compatible with findings from two cohort studies of
      Czech uranium miners. This similarity holds in more complex models that include
      modifying effects of age and time since exposure. In addition, an alternative
      description of the risk in terms of lifetime risk was used. This approach
      provides summarized characteristics, in which modifying effects of time and age
      are incorporated. The attributive risk derived from the lifetime relative risk is
      proportional to cumulated exposure observed in both tin and uranium miners. On
      the other hand, the expected life shortening of 19 years among radiation induced
      deaths is similar in these studies.

PMID- 15254656
TI  - Lymphocyte subpopulations and immunoglobulin levels in Hodgkin's disease
      survivors.
AB  - We investigated the frequency of lymphocyte populations (CD3+ /T lymphocytes/,
      CD4+ /helpers/, CD8+ /suppressor and cytotoxic/, CD3- CD16+ /NK cells/, CD3+ HLA
      DR+ /activated T lymphocytes/, and CD20+ /B lymphocytes/) and immunoglobulin G,
      A, M, and E levels in a group of two hundred twenty nine Hodgkins disease long
      term survivors. The most frequent pathological findings were increased IgE
      levels, decreased CD3+ and CD4+ proportions, an increased CD20+ proportion and
      especially a low CD4/CD8 proportion. Decreased CD3+ and CD4+ and increased CD20+
      proportions were more frequently found in the group with recurrent infections.
      IgM and IgA levels were positively correlated with plasmatic cholesterol and
      triacylglycerols levels. We suppose that immunological defects (increase of IgE
      levels, decreased T and helper lymphocytes) in Hodgkins disease survivors are
      inherent and are not related to atopy. Examination of lymphocyte subpopulations
      may be helpful in the prediction of an increased risk of recurrent infections.

PMID- 15254657
TI  - Bactericidal capacity of platelets in gastric cancer patients.
AB  - The aim of this study was to evaluate bactericidal capacity of platelets in
      patients suffering from gastric cancer. Number of platelets and their
      bactericidal activity were measured in 32 cancer patients (divided into 2 groups:
      I--resectable cancer, II--non-resectable one) and 32 normal donors. In group I
      the number of platelets was 259.136+/-84.459 x 103/microl. It was increased
      comparing to the normal donors 193.219+/-55.493 x 103/microl. After the surgery
      increase in platelet number was observed (472.05+/-111.772 x 103/microl). In
      group II an increased number of platelets was observed (265.1+/-81.813 x
      103/microl) and it was maintained in a post-operative period: 234.2+/-54.141 x
      103/microl. In group I bactericidal capacity of platelets was 2.25+/-7.33%,
      whereas it increased significantly after the surgery--4.7+/-7.46%. In group II,
      it was 8.6+/-17.61% before and 4.72+/-4.76% after the surgery. In normal donors
      this ability was 21.66+/-16.66. In gastric cancer patients increased platelet
      number was observed. Significant increase in platelets number occurred after a
      radical tumor removal. Decreased bactericidal activity of platelets was noticed
      in gastric cancer patients. After surgical removal of the tumor, platelets partly
      reclaimed bactericidal capacity. In patients presenting disseminated gastric
      cancer, bactericidal capacity of platelets could be permanently impaired.

PMID- 15254658
TI  - Serum levels of soluble E-selectin in colorectal cancer.
AB  - Adhesion molecules play an important role in tumor metastasis. E-selectin can
      support adhesion of colon cancer cells through the recognition of specific
      carbohydrate ligands. High levels of soluble E-selectin (sE-selectin) had been
      reported in melanoma and some epithelial tumors, especially in colorectal
      carcinoma. The concentrations of the sE-selectin were investigated in serum
      samples of 64 patients (32 men and 32 women) with colorectal cancer and 16
      healthy subjects. Median age was 57 (range 20-75). Nineteen patients were staged
      as Dukes D, 9 of whom had liver metastasis. Serum levels of sE-selectin were
      determined by ELISA. In the study group, sE-selectin concentrations (mean+/-SE,
      ng/ml) were not significantly elevated, compared with the control group (41.09+/
      4.57 in the control group and 43.80+/-1.88 in patients, p>0.05). Mean sE-selectin
      levels were 42.27+/-1.85 in non-metastatic and 47.42+/-4.57 in metastatic
      patients (p>0.05). Serum concentrations of sE-selectin were significantly
      elevated in patients with colorectal cancer metastatic to liver (59.07+/-7.52) in
      comparison to other patients without liver metastasis (p=0.013). There were no
      significant correlations between sE-selectin levels and other parameters such as
      age of patients, stage of disease, histopathological differentiation or
      localization of primary tumor. Elevated sE-selectin levels were confirmed as
      correlating with poor overall survival. In conclusion, sE-selectin concentrations
      may not be used as a predictive marker of metastasis in colorectal carcinoma, but
      high levels of sE-selectin may support diagnosis of liver metastasis.

PMID- 15254659
TI  - Immunohistochemical detection of the hMLH1 and hMSH2 proteins in hereditary non
      polyposis colon cancer and sporadic colon cancer.
AB  - Defects in DNA mismatch repair system are involved in carcinogenesis of sporadic
      and inherited human cancers. We assessed the feasibility of using
      immunohistochemistry to detect tumors with DNA mismatch repair deficiency. We
      analyzed 81 samples (74 colon cancers (CC), 1 colon dysplasia and 6 extracolonic
      cancers) for hMLH1 and hMSH2 protein expression, microsatellite instability (MSI)
      and/or mutational analysis. A meta-analysis of the published data on
      immunohistochemistry of hMLH1/hMSH2 proteins was performed. Sensitivity and
      specificity of the method was calculated. Twenty four of 29 tumors from
      hMLH1/hMSH2 mutation carriers and 10 of 13 sporadic high frequency MSI tumors
      lost one of the proteins. None of the 42 tumors with stable microsatellites or
      low frequency MSI lost the proteins. Based on literature review of 49
      publications on colorectal cancer, hMLH1 immunohistochemistry was able to detect
      136 of 154 tumors from hMLH1 germline mutation carriers (the sensitivity of 88.3%
      [95%CI, 85.8-90.8%]), hMSH2 immunohistochemistry detected 99 of 109 tumors from
      hMSH2 mutation carriers (the sensitivity of 90.8% [95%CI, 88.5-93.1%]), and
      hMLH1/hMSH2 immunohistochemistry identified 1262 of 1382 tumors with high
      frequency microsatellite instability not correlated with mutational analysis (the
      sensitivity of 91.3% [95%CI, 90.4-92.2%]). The specificity of the method was
      99.4% (95%CI, 99.2-99.6%). In conclusion, immunohistochemistry of hMLH1 and hMSH2
      proteins is a useful method to predict the presence of mismatch repair
      deficiency, although its sensitivity is lower than that of MSI analysis.

PMID- 15254660
TI  - Are stromal fibroblasts from cervical tumors suitable to predict normal tissue
      radiation reaction?
AB  - We examined the effect of gamma-irradiation (4 Gy) alone or combined with
      estrogen (17beta-estradiol 15 microM) treatment on the radiation response of
      stromal fibroblasts from cervical tumors. The fibroblasts were derived from
      tumors of 9 younger (<50 years) and 9 older (>50 years) cervical cancer patients.
      A normal fibroblast GSH+/+ cell strain was used as a reference cell. The end
      points examined 2 days after irradiation were cell cycle distribution and
      apoptosis as measured of the cellular response to gamma-radiation. The response
      of examined fibroblast groups to gamma-rays alone was comparable but apoptotic
      death was more marked in fibroblasts derived from the younger patients with TNM
      1+2 tumors than from the older ones. There was a considerable estrogen effect on
      the response to gamma-rays that differed between stromal fibroblasts from the
      examined age groups and was dependent on the tumor stage. In particular, we found
      a marked decrease in the number of apoptotic cells and debris after estrogen +
      irradiation, as compared to irradiation alone, only in younger patients and TNM
      1+2 tumors. These results indicate that the response of stromal fibroblasts to
      gamma-rays to a considerable extent depends on donors age and tumor stage. Since
      stromal fibroblasts have been used for prediction of normal tissue late effects
      in patients treated with radiotherapy, we conclude that they may not be an
      adequate model for this purpose.

PMID- 15254661
TI  - Correlation of vascular endothelial growth factor (VEGF) and CEA with
      clinicopathological variables in colorectal cancer patients.
AB  - The aim of the presented study is to analyze VEGF levels and its correlation with
      the clinicopathological characteristics of patients with colorectal carcinoma.
      Thirty-three patients with colorectal adenocarcinoma and 10 healthy controls were
      evaluated by estimation of VEGF and CEA levels and correlation with
      clinicopathological features. The serum VEGF and CEA concentrations of colorectal
      patients were higher than the healthy controls (p<0.05). Patients in advanced
      stage had high levels of both markers but these differences were not
      statistically significant. There was a positive correlation between both markers
      and, tumor size and peritumoral vascular invasion (PVI) but when compared VEGF
      with CEA, VEGF had a stronger correlation. Diagnostic sensitivity of VEGF for
      colorectal carcinoma was higher than the sensitivity of CEA and combining both
      markers the sensitivity to predict colorectal carcinoma was higher than of each
      marker alone. Our study indicated that VEGF compared to CEA had a higher
      diagnostic sensitivity for colorectal carcinoma and might provide even additional
      information about tumor features.

PMID- 15254662
TI  - Adrenal myelolipoma. 6 cases and a review of the literature.
AB  - Adrenal myelolipoma is an uncommon, benign and hormonally inactive tumor. Most
      lesions are asymptomatic and usually are discovered incidentally at autopsy
      studies. Authors report on 6 patients (5 women, 1 man) with adrenal myelolipomas
      (5 right, 1 left), analyze their morphological findings and association with an
      adrenal hormonal overproduction. Five of the patients underwent surgery because
      of tumor size, in 3 of them histological evaluation confirmed myelolipoma and in
      2 cases an adrenocortical adenoma with foci of myelolipoma. All the patients were
      asymptomatic and in 4 cases hormonal overproduction was not found. One female
      patient has oveproduction of dehydroepiandrosteron-sulphate (DHEAS) indicating a
      3beta hydroxylase deficiency in this tumor and 1 patient has primary
      aldosteronism with a histological finding of an association of adrenocortical
      adenoma with foci of myelolipoma. Neither Cushings syndrome nor congenital
      adrenal hyperplasia were present in our group of patients.

PMID- 15254663
TI  - Choroid plexus tumors: a review of 28-year experience.
AB  - The aims of the study were to review the patients with choroid plexus tumor (CPT)
      treated in Slovenia between 1972-1999, to calculate the incidence of CPTs, and to
      evaluate treatment results in respect to tumor histology and mode of therapy.
      Cancer Registry of Slovenia database was used for patients identification.
      Histological specimens and medical records were reviewed. Twelve patients (7
      females, 5 males), 0.8-43 years old (median 6.1 years; <15 years: 10/12,83%) with
      CPT, representing 0.36% of all intracranial tumors registered during the period
      under study, were identified. Considering children less than 15 years old only,
      the corresponding percentage was 3.69. There were eight papillomas (CPPs) and
      four carcinomas (CPCs) with no difference in age distribution between the groups.
      Of seven patients with gross tumor resection in CPP group, one patient died of
      postoperative meningitis and one had local recurrence 1.6 years after surgery;
      the latter is disease-free 17.9 years after re-operation. One patient with
      macroscopic residue after surgery is alive and asymptomatic after 16.5 years. In
      the CPC-group, only the patient who received adjuvant BEP chemotherapy and
      craniospinal irradiation following incomplete surgery is alive with no signs of
      disease after 6.5 years. Ten-year disease-specific survival for all CPTs and for
      CPP subgroup was 73% and 100%, respectively. In Slovenia, CPTs represent 0.36% of
      intracranial tumors. In children, the incidence is 3.69%. CPPs are twice as
      frequent as CPCs. In CPPs, the treatment of choice is surgery alone. After
      incomplete surgery, wait-and-see policy seems to be justified. For CPCs, adjuvant
      multiagent chemotherapy and craniospinal radiotherapy following surgery should be
      considered.

PMID- 15254664
TI  - Advanced tracheal carcinoma--a therapeutic significance of HDR brachytherapy in
      palliative treatment.
AB  - The purpose of this study was to determine the benefit of high dose rate
      endotracheal brachytherapy as an exclusive palliative treatment of obstructive
      tracheal cancer. Thirty-five patients with advanced tracheal carcinoma were
      treated between May 1999 and March 2001 in Greatpoland Cancer Center. They were
      qualified for brachytherapy due to life-threatening situations. Fourteen patients
      were irradiated using three fractions 7.5 Gy each one every week, six patients
      received three fractions 10 Gy each one every week and fifteen patients received
      one fraction of 10 Gy. Survival time was compared with chosen clinical factors
      (age, sex, Karnofsky status, tumor location, lymph nodes involvement and percent
      of obturation) and prescribed dose. The median survival (Kaplan-Meier) for all
      patients was 6.6 months. Patients with an endoscopically controlled complete
      remission 4 weeks after the treatment had a significantly better survival in
      comparison to patients with a partial remission or no change of tumor size
      (p=0.0003). Univariate analysis revealed significant difference between patients
      with Karnofsky score equal with 60 or lower (28/35, 80%) and higher than 60
      (7/35, 20.0%) (p=0.005). Difference between the grade of tumor obturation (more
      than 60% of tracheal lumen (27/35, 77.1%), 60% or lower (8/35, 22.9%) was found
      in univariate analysis (p=0.04). In multivariate analysis statistically important
      prognostic factor for survival was Karnofsky score (p=0.04). Statistical analysis
      revealed no differences in survival according to sex and age (p=0.43 for age,
      p=0.19 for sex), tumor localization (p=0.13), lymph node involvement (p=0.48) or
      fractionation scheme (p=0.62). Exclusive HDR brachytherapy of advanced tracheal
      carcinoma was a safe palliative method of treatment and caused in many patients
      prolonged survival and improved quality of life. Most important prognostic factor
      for survival, confirmed in both univariate and multivariate analysis, was
      Karnofsky score.

PMID- 15254665
TI  - Expression of p65 gene in experimental colon cancer under the influence of 5
      fluorouracil given alone and in combination with hormonal modulation.
AB  - The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given
      separately or together, on p65 gene expression in murine Colon 38 cancer was
      investigated by RT-PCR method. The findings were compared with cell proliferation
      determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by
      TUNEL method and tumor mass. It was found that in the control group (mice bearing
      colon cancer without treatment) the expression of p65 gene was present in 57% of
      investigated samples. In the groups treated with TAM or LAN p65 gene expression
      was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these
      substances increased apoptotic index in Colon 38 cancer and LAN also decreased
      the proliferation index. After a combined treatment with TAM and LAN a percentage
      of p65 positive cases was similar to that of the control group and equaled
      approximately 60%. This treatment did not increase proapoptotic effects of these
      drugs, and even reduced the antiproliferogenic effect of LAN. In the group
      treated with 5-FU and LAN p65 gene expression was also close to the control value
      (about 66%). Similarly in this group the combined treatment with these two drugs
      did not cause any favorable effect on proliferation and apoptosis. Moreover, in
      this group even reduced antiproliferogenic effect of LAN was observed. In the
      group with 5-FU alone the expression of p65 was present in about 80% of samples.
      The treatment with 5-FU increased apoptotic index and did not change
      proliferation. In the group treated with a combination of TAM and 5-FU all
      analyzed cases showed the presence of p65 gene expression. Previously, we
      observed in this group the most pronounced and synergistic effect of these
      substances on the inhibition of cell proliferation and tumor mass reduction.
      Based on these findings we conclude that p65 gene expression in murine Colon 38
      cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal
      modulation (TAM and LAN).

PMID- 15254666
TI  - Contribution of flow cytometric immunophenotyping and bone marrow trephine biopsy
      in the detection of lymphoid bone marrow infiltration in non-Hodgkin's lymphomas.
AB  - The bone marrow (BM) is a frequent site of involvement in non-Hodgkins lymphomas
      (NHL) and evidence of an infiltrated BM may implicate different therapeutical
      regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is
      included in the assessment of patients with NHL and used as an adjunct to
      morphologic evaluation in the staging of lymphoma. The aim of the study was to
      compare flow cytometric immunophenotyping of BM and paraffin section staining of
      BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of
      bone marrow and immunohistochemical paraffin section staining of bone marrow
      biopsies in 53 B- and T-cell lymphoma patients were performed. We used the
      following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4,
      CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light
      chain. Unilateral BM trephine biopsies were obtained in all cases, fixed,
      decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was
      found in 24 cases; flow immunophenotyping identified 26 cases with NHL:
      morphology-positive/flow-positive (n=21), morphology positive/flow-negative
      (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow
      negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric
      immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%.
      Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful
      for assessment of bone marrow infiltration, especially in B-cell disorders. Both
      trephine biopsies and flow cytometry are better than single investigation for
      detection of infiltration in NHL.

PMID- 15254667
TI  - Expression of glucose transporter GLUT-1 and estrogen receptors ER-alpha and ER
      beta in human breast cancer.
AB  - We attempted to describe a GLUT-1 expression in breast cancer and characterize
      correlation between GLUT-1 and ERs alpha and beta expression as well as correlate
      this with clinicopathologic features. Sixty-nine patients were involved in the
      study. GLUT-1, ER-alpha and ER-beta immunocytochemistry was performed using the
      streptavidin- biotin method. Thirty-seven (53.6%) out of total 69 were GLUT-1
      positive. Of GLUT- 1 positive 45.3% were ER-alpha-positive, whereas 81.3% of ER
      alpha-negative were GLUT-1 positive. Statistically significant correlation was
      observed between GLUT-1 and ER-alpha expression status but neither between GLUT-1
      and ER-beta nor with clinicopathologic features. No statistically significant
      correlation was found between expression level (expressed as immunocytoreactive
      score) of GLUT-1, ER-alpha and ER-beta. Since most of ER-alpha-negative (81.3%)
      were GLUT-1 positive and significant correlation exists between the two receptors
      it is reasonable to assume that some functional relation might exists between the
      expression of two receptors.

PMID- 15254668
TI  - Expression of the multidrug resistance-associated protein 1 (MRP1) and the lung
      resistance-related protein (LRP) in human lung cancer.
AB  - Fifty lung cancer samples (41 non-small cell lung cancer-NSCLC and 9 small cell
      lung cancer-SCLC) were immunohistochemically analyzed for lung resistance-related
      protein (LRP) and multidrug resistance-associated protein 1 (MRP1) expressions
      which were then correlated with histopathological subtype of the tumor. To detect
      these proteins, monoclonal antibodies LRP-56 and MRPm6 were used. NSCLC samples
      were divided into two groups, adenocarcinomas (17 samples) and squamous cell
      carcinomas (24 samples). Four categories of LRP and MRP1 quantity were
      distinguished: +++ = high level--90--100% of positive cells, ++ = lower level--10
      -90% of positive cells, + = low level--up to 10% of positive cells, - = negative
      cells--0% of positive cells. Within the NSCLC group the most samples (36/41) had
      the similar level of LRP and MRP1. Significantly higher expression of both
      proteins was observed in the adenocarcinomas in comparison with squamous cell
      carcinomas. The lowest positive staining for LRP and MRP1 proteins has been found
      in SCLC. It is suggested that our finding can confirm the overall empirical
      clinical knowledge about much higher chemosensitivity of untreated SCLC comparing
      to NSCLC.

PMID- 15254669
TI  - Gene expression during camptothecin-induced apoptosis in human myeloid leukemia
      cell line ML-2.
AB  - Malignant cell proliferation and accumulation depends on the balance between the
      rates of cell production and cell death. Recent evidence indicates that apoptosis
      is important in the development of cancer. Apoptosis is strictly controlled by
      various regulators, which can take part in the apoptotic process, proliferation
      and differentiation alike. Apoptosis was induced in myeloid cell line ML-2 by
      camptothecin, an inhibitor of topoisomerase I. After 18 hours of induction by
      camptothecin 50% of cells were apoptotic. The apoptotic effect of CAM was
      reversible in the cells studied. The induction of apoptosis influenced the
      expression of apoptosis and cell cycle regulators as detected by cDNA arrays, RT
      PCR or Western blotting. According to cDNA arrays e.g. bax, bfl1, bak, pRb2, c
      jun, jun-B were upregulated, and cdk4, cyclin B1, wee1, CRAF1, DP1 were
      downregulated. A number of other regulators like p21 and cdc25A, as well as some
      other genes linked with apoptosis, as p53 and the bcl-2 family, were up- or down
      regulated as determined by real-time PCR. Changes in gene expression were found
      not only in the group of regulators of apoptosis and the cell cycle, but also
      among regulators of differentiation.

PMID- 15254670
TI  - Relation of P-glycoprotein expression with spontaneous in vitro apoptosis in B
      cell chronic lymphocytic leukemia.
AB  - Prolonged lifespan of monoclonal lymphocytes in B-cell lymphocytic leukemia (B
      CLL) arises from their resistance to programmed cell death. In contrast, when
      cultured in vitro, B-CLL tumour cells rapidly undergo apoptosis. There is
      mounting evidence that P-glycoprotein (P-gp), an adenosine triphosphate-binding
      cassette (ABC) family transporter, plays a significant role in the regulation of
      apoptosis induced by various stimuli. Since P-gp is commonly expressed in B-CLL
      cells, we aimed to establish whether its expression level influences resistance
      to spontaneous apoptosis in B-CLL. For that purpose, P-gp expression by UIC2
      antibody staining and P-gp activity by rhodamine 123 (Rh123) efflux in presence
      or absence of P-gp inhibitor verapamil were studied in peripheral blood
      lymphocytes obtained from 43 previously untreated B-CLL patients. Simultaneously,
      the percentage of cells undergoing spontaneous in vitro apoptosis (apoptotic
      index, AI) by means of activation of caspases and annexin-V-based assays was
      evaluated. The AI were higher in B-CLL cells than in normal peripheral blood
      mononuclear cells (medians of AI 27.7% vs 3.9%, p=0.0001 and 34.7% vs 7.4%,
      p=0.0038, in 24 and 48-hour culture respectively). The AI were also higher among
      female patients as compared to male patients (medians: 29.7 vs 19.2 p=0.048).
      Interestingly, we found moderate inverse correlation between P-gp protein
      expression and AI after 24-hour culture in analysed B-CLL samples (r= -0.36,
      p=0.019). Moreover, P-gp positive B-CLL samples expressed significantly higher AI
      than P-gp negative samples with an arbitrary cut-off at Kolmogorov-Smirnov
      statistics D-value 0.2 (medians of AI 18.4% vs 29.7%, p=0.026). Based on these
      results we suggest that P-gp expression has some protective effect on B-CLL cell
      survival in vitro. The difference in the rates of spontaneous apoptosis among
      male and female patients may contribute to gender-dependent variations in
      clinical outcome in B-CLL.

PMID- 15254671
TI  - Potentiation of doxorubicin-induced apoptosis and differentiation by indomethacin
      in K-562 leukemia cells.
AB  - In this study we have examined the antitumor effect of combined administrations
      of indomethacin (IND) with doxorubicin (DOX) on growth of K-562 leukemia cells.
      Although, as single drug treatment, only high concentrations of IND reduced
      growth (>200 microM) and induced apoptosis (>800 microM) of the K-562 cells, a
      synergistic effects on DOX-induced cell growth inhibition, apoptosis and
      differentiation were observed during the co-administration of DOX with 10 microM
      IND. Cells treated with this combination had elevated GSHt level compare to DOX
      treated cells. Modulation of GSHt level of DOX-treated cells with Cd2+ ions or
      BSO confirmed its important role in processes of DOX-induced differentiation.
      Results of this study showed that IND has a positive effect on therapeutic
      efficacy of DOX, and could be a perspective modulator in cancer chemotherapy.

PMID- 15254672
TI  - Evaluation of angiogenesis, p-53 tissue protein expression and serum VEGF in
      patients with endometrial cancer.
AB  - Endometrial carcinoma occurs mostly in post-menopausal women. Classical methods
      of prognostication, as FIGO stage and histopathologic grade, could be improved by
      applying additional techniques, utilizing molecular biology and immunochemistry.
      p-53 tumor suppressor gene, the most commonly mutated gene in human cancers has
      been shown to play an important role in the biology of gynecologic carcinomas.
      Angiogenesis, a process of formation of new vessels, being connected to tumors
      progression and metastatic potential was shown to be linked with tumor suppressor
      genes expression. The aim of the study was to evaluate relationships between
      intensity of tumor angiogenesis, serum levels of Vascular Endothelial Growth
      Factor (VEGF) and tissue p-53 protein expression in endometrial adenocarcinoma.
      Angiogenic Point's Density (APD) was calculated in hot spots areas using the
      morphometric appliance. For detection of p53 protein in tumor samples, LSAB + Kit
      Alkaline Phosphatase (DAKO) was used. VEGF levels were assessed in patient's
      blood sampled before the operation. Overexpression of p53 protein was found in
      tumor tissue in 35.2% of cases and mean angiogenic points density was greater in
      p53 positive cases. Serum levels of VEGF were above the cut off level in 54.5% of
      patients, in those cases angiogenesis was also elevated. In cases of p53
      overexpression, VEGF levels tended to be greater as compared with p53 negative
      cases. In conclusion, our study demonstrated that angiogenesis was more intensive
      in p53 positive cases, confirming the hypothesis of tumor suppressor-gene
      regulation of the process of neovascularization. Serum levels of VEGF were
      borderline-significantly higher in cases of p53 overexpression, they were also
      correlated to the angiogenesis. Joint assessment of angiogenesis and tumor
      suppressor genes expression may contribute to reliable evaluation of the biology
      of endometrial carcinoma.

PMID- 15254673
TI  - Genotoxicity evaluation of pesticide formulations containing alachlor and
      atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by
      comet assay.
AB  - Every year, in the European countries more than 2 million tons of pesticides are
      released into the environment. More than 60% of those substances appear to be
      herbicides. Due to extensive production and application of this chemical their
      putative detrimental effect on life should be known and minimized. In this study
      we applied the comet assay on blood and 4 mouse organs (kidney, liver, bone
      marrow, and spleen) to evaluate possible genome damage caused by two pesticide
      formulations (Bravo and Gesaprim) containing alachlor and atrazine as active
      ingredients. Five male CBA mice were assigned to each of 4 treatment groups and
      control group. Bravo and Gesaprim were injected intraperitoneally once. Two
      different doses of Bravo were used: 0.031 ml/kg and 0.021 microl/kg, so that
      doses of alachlor mice received within the pesticide formulation given were 15
      mg/kg and 0.01 mg/kg. Also Gesaprim was given at two different doses: 1.08 ml/kg
      and 0.07 microl/kg so that the doses of atrazine contained within the pesticide
      formulation given were 540 mg/kg and 3.5 x 10(-2) mg/kg. Mice were sacrificed 24
      hours after treatment. Alkaline comet assay on the blood samples, kidney, liver,
      bone marrow and spleen was performed. Statistically significant (p<0.01) increase
      of tail length for all 5 tissues examined in mice treated with both Bravo and
      Gesaprim compared to the control was found. For both pesticides DNA of kidney and
      liver showed largest increase in migration. Also, distribution of tail length
      values for Bravo and Gesaprim for all mouse tissues examined showed a shift to
      the right when compared to the controls.

PMID- 15254674
TI  - Mammaglobin A, a novel marker of minimal residual disease in early stages breast
      cancer.
AB  - Mammaglobin A, in contrast to other factors, is a breast specific member of
      uteroglobin gene family. Expression is restricted to normal and neoplastic breast
      epithelium. A highly homologous mammaglobin B is not specific to breast tissue.
      In this pilot feasibility study we examined expression of both markers for
      minimal residual disease in the bone marrow of patients with breast cancer. We
      obtained bone marrow aspirates of 34 patients with stage I (41%), II (56%) and
      III (3%) breast cancer who underwent either immediate complete resection of the
      tumor or neoadjuvant therapy with subsequent curative surgery. mRNA was isolated
      using QIAamp RNA blood mini kit (Qiagen). Subsequently two-step nested RT-PCR for
      the expression of mammaglobin A and mammaglobin B was performed. Mammaglobin A
      was detected in samples from 4 (12%) out of 34 patients. None of the specimens
      was positive for mammaglobin B. With a median follow-up of 21 month we observed
      only 2 recurrences, one in patient with mammaglobin A positive bone marrow.RT-PCR
      assay for mammaglobin A may be a useful tool for detection of occult breast
      cancer cells in the bone marrow. Clinical and prognostic relevance of minimal
      residual disease should be further investigated.

PMID- 15254675
TI  - Serum hepatocyte growth factor and interleukin-6 levels can distinguish patients
      with primary or metastatic liver tumors from those with benign liver lesions.
AB  - Hepatocyte growth factor (HGF) is a potent stimulator of angiogenesis and cancer
      metastasis. Interleukin-6 (IL-6) is a pleiotropic cytokine that can act as an
      autocrine or paracrine growth factor in various tumor cells. In this study, we
      investigated the role of serum HGF and IL-6 levels to distinguish primary or
      metastatic liver tumors from benign liver lesions. Serum HGF and IL-6 levels were
      measured in 64 cancer patients and 12 healthy controls. Patients were divided
      into 5 groups: Group-1 (n=24): Breast cancer patients in complete remission
      without any liver lesion, Group-2 (n=8): Breast cancer patients in complete
      remission with benign liver lesion, Group-3 (n=10): Breast cancer patients with
      liver metastasis, Group-4 (n=11): Metastatic breast cancer patients without liver
      metastasis, Group-5 (n=11): Patients with hepatocellular carcinoma. Group-6
      (n=12): Healthy controls. Serum HGF levels were found to be higher in group-5
      (606.4+/-255.8 pg/ml) than those in group-1 (*305.6+/-42.3 pg/ml), group-2
      (*293.9+/-44.8 pg/ml), group-4 (**358.4+/-81.9 pg/ml) and group-6 (*305.8+/-24.9
      pg/ml) (*p<0.001, **p<0.05). Patients in group-3 (448.9+/-157.3 pg/ml) had higher
      serum HGF levels than those in group-1, group-2 and group-6 (p<0.05). Serum IL-6
      levels were found to be higher in group-5 (54.9+/-37.4 pg/ml) than those in group
      1 (9.7+/-6.4 pg/ml), group-2 (9.5+/-4.8 pg/ml), group-4 (17.6+/-19.6 pg/ml) and
      group-6 (12.6+/-5.2 pg/ml, p<0.05). Patients in group-3 (32.5+/-36.9 pg/ml) had
      higher serum IL-6 levels than those in group-1, 2 and group-6, but these were not
      statistically significant (p>0.05). This study showed that primer and metastatic
      liver tumors had higher serum HGF and IL-6 levels than other patients and
      controls. Measurements of these markers in serum may be used to distinguish
      patients with primer liver tumors or breast cancer patients with liver metastasis
      from those with benign liver lesions or non-metastatic patients.

PMID- 15254676
TI  - Distribution of the extracellular matrix glycoproteins in ependymomas--an
      immunohistochemical study with follow-up analysis.
AB  - The extracellular matrix (ECM) plays a critical role in influencing the
      biological behavior of brain tumors and the diagnostic detection of ECM
      components in ependymomas might be of prognostic value. In the present study we
      evaluated immunohistochemically the expression of a spectrum of ECM glycoproteins
      (tenascin, vitronectin, fibronectin, laminin, collagen types II, IV and VI) in a
      series of 36 pediatric intracranial ependymomas. The distribution of the ECM
      glycoproteins was evaluated both within the tumor tissue and at the tumor
      invasion front, and the prognostic value of the results was tested in a survival
      analysis. The expression of most of the ECM glycoproteins was associated only
      with blood vessels. Tenascin and vitronectin were found in a more diffuse pattern
      around the tumor cells and at the tumor invasion fronts of several cases. The
      progression-free survival was significantly decreased for patients with tenascin
      positive tumors (in any of the studied compartments) and for the tumors with
      vitronectin accumulation at their invasion fronts. In one ependymoma containing
      foci of cartilage with metaplastic ossification we demonstrated that collagen
      types II and VI and tenascin were present in ECM of both the cartilage and the
      ependymoma, and were accompanied by areas of necrosis and dystrophic
      calcifications. We suggest, that the rare simultaneous production of the specific
      ECM components might lead to the formation of chondroid areas in ependymomas. An
      abundant production of some ECM glycoproteins (tenascin and vitronectin) is
      present in a proportion of ependymomas and its immunohistochemical detection is
      of prognostic relevance.

PMID- 15254677
TI  - Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait.
AB  - Cytogenetic analysis was successfully performed at the time of diagnosis in 45
      patients with de novo acute myeloid leukemia, including 10 children and 35
      adults. In approximately 73% of AML patients (35 patients) clonal chromosome
      abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had
      apparently normal karyotypes. Recurring aberrations found in 22 of patients with
      abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22),
      inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of
      chromosome changes was observed in AML-M3. The occurrence of the classical
      cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients
      previously not described miscellaneous clonal chromosomal abnormalities were
      detected. Clonal chromosomal abnormalities detected in AML have shown
      correlations between specific recurrent chromosomal abnormalities and clinico
      biological characteristics of the patients, therefore have been repeatedly shown
      to constitute markers of diagnostic and prognostic significance. Moreover,
      ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in
      AML and contribute to the identification of novel genes involved in the
      development of cancer, which can lead to better understanding of the disease
      pathogenesis.

PMID- 15254678
TI  - Biologically effective doses in radiotherapy of cervical carcinoma*.
AB  - Presented study evaluates biologically effective dose (BED) in patients receiving
      low-medium dose-rate (LDR/MDR) brachytherapy (BRT) plus external beam
      radiotherapy (XRT) based on tumor cell proliferation values in cancer of the
      cervix patients. This study includes 229 patients treated entirely by
      radiotherapy at the Centre Oncology in Krakow. Doses to Point A were estimated
      for total treatment for each brachytherapy insertion. BED3 were calculated for
      reference points in the rectum. The linear quadratic equation was used to
      calculate BED, which is proportional to log cell kill, and the normalized total
      dose (NTD), that is, equivalent to a 2 Gy fraction schedule. In BEDs 10
      calculation overall treatment time for each patient. Tumor proliferation rate was
      based on Bromodeoxyuridine labeling index (BrdUrdLI) assessed on biopsy material
      before beginning the radiotherapy. Total BED at those points was summed for each
      patient. The medium overall treatment time was 90 days (range 30--210). The mean
      calculated total BED for point A for tumour and "early reactions" was equal to
      104.0 Gy10 and 229.0 Gy3 for the rectum, equivalent to NTD=86.6 Gy and 137.4 Gy
      in 2 Gy fractions, respectively. Kaplan-Meier analysis revealed that age >50
      years, higher than mean BRBEDs and totBEDs doses, gaps in treatments shorter than
      40 days and disease free survival (DFS) was significant prognostic factor for
      overall survival. In the multivariate Cox anaysis age >50 years, BRBED10 >77 Gy
      and gaps ?40 days appeared to be significant for overall survival. None of the
      examined parameters was significant for tumor control. However, patients age and
      shorter gaps in the treatment were predictive for DFS.

PMID- 15254679
TI  - Ectopic expression of DICE1 suppresses tumor cell growth.
AB  - The tumor suppressor gene DICE1 is located within a previously reported critical
      region of loss of heterozygosity on chromosome 13q14.3. Expression of the
      remaining DICE1 allele is down-regulated in non-small cell lung carcinomas.
      Ectopic expression of DICE1 cDNA by DICE1-green fluorescent protein fusion
      constructs resulted in inhibition of colony formation of human non-small cell
      lung carcinoma cell line SK-MES-1 and NCI-H520 and prostate carcinoma cell line
      DU145. In IGF-IR transformed Balb/c 3T3, DICE1 substantially sup-pressed growth
      in soft agar. These results demonstrate that DICE1 has a growth-suppressing
      activity and interferes with anchorage-independent growth of IGF-IR transformed
      tumor cells dependent upon IGF-I signaling.

PMID- 15254680
TI  - Histopathology of ventricles, coronary arteries and mast cell accumulation in
      transverse and longitudinal sections of the rat heart after irradiation.
AB  - The aim of the study was to compare cross sections with longitudinal sections in
      histopathological examination of the rat heart after irradiation, to find the
      most optimal method for the detection of cardiac radiation injuries. For this
      purpose, rats were irradiated locally on the heart with a single dose of 0 or 20
      Gy. At different time points after irradiation, hearts were perfused and cut into
      longitudinal or cross sections. In both sections, several histopathological
      changes were scored on a graded scale between 0 and 3. Mast cells, which are
      thought to play a role in tissue remodelling, were counted. After 20 Gy,
      frequently occurring lesions were most severe in the upper half of the ventricles
      and the septum. These lesions could only be detected when using longitudinal
      sections, resulting in a higher total histopathological score than the
      examination of a single cross section. From 3 months onwards, changes in coronary
      arteries of irradiated hearts included endothelial cell loss, a loss of smooth
      muscle cells and fibrosis in media and adventitia. Up to 1 month after
      irradiation, mast cell densities of the left and right ventricles were decreased
      after 15 and 20 Gy, compared to time-matched controls, followed by increases from
      3 months onwards. In the left ventricle, mast cell densities correlated with
      myocardial degeneration and fibre loss. The results of this study show that the
      usage of a single longitudinal section in the histopathological examination of
      the irradiated rat heart leads to the recognition of more severe injuries,
      including myocardial degeneration and fibrosis, in ventricular tissue than the
      usage of a single midventricular cross section. Morphological changes observed in
      coronary arteries of irradiated hearts might lead to a decreased compliance of
      the coronary artery wall. Further investigation is needed to determine the role
      of mast cells in cardiac tissue remodelling after irradiation.

PMID- 15254681
TI  - Melanoma metastasis is associated with enhanced expression of the syntenin gene.
AB  - Primary cutaneous melanomas and melanoma metastases were examined for
      differential gene expression using subtractive suppression hybridization in a
      search for any genes associated with metastasis. Generating a subtracted library
      of candidate genes up-regulated in melanoma metastases, this library contained 8
      different cDNAs, among them a cDNA fragment of the syntenin gene which was
      overexpressed in further independent melanoma resection specimens on cDNA
      Southern blots when compared to acquired melanocytic nevi from which melanomas
      are known to arise. Upon immunohistochemistry, the syntenin protein expression
      was detected in the cytoplasm of primary cutaneous melanomas and melanoma
      metastases. Melanoma metastases exhibited higher proportions of tumour cells
      positive for syntenin immunostaining in comparison to acquired melanocytic nevi
      or non-metastasizing primary melanomas which was statistically significant. In
      addition to melanoma, gastric cancer tissues exhibited a higher syntenin mRNA
      expression on a matched tumour/normal cDNA array than their normal counterparts
      which was statistically significant. Altogether, we here first describe the
      detection of the syntenin protein in resection specimens of melanocytic lesions.
      We conclude that melanoma metastasis is associated with increased expression of
      the syntenin gene which may participate in signal transduction and cell adhesion
      via the multifunctional protein-binding properties of its tandem PDZ domains.

PMID- 15254682
TI  - Expression of c-erbB receptors, MMPs and VEGF in squamous cell carcinoma of the
      head and neck.
AB  - Head and neck squamous cell carcinomas (HNSCC) are characterized by a marked
      propensity for local invasion and cervical lymph node metastasis. The aim of this
      study was to investigate the expression of epidermal growth factor receptor
      (EGFR), c-erbB-2, vascular endothelial growth factor (VEGF) and matrix
      metalloproteinases (MMPs) in tumor samples of 91 HNSCC patients, and to study a
      possible correlation to various clinico-pathologic parameters. The expression of
      EGFR, c-erbB-2, VEGF, MMP-2, -3 and -9 was analyzed in the same paraffin embedded
      tissue by semi-quantitative immunohistochemical staining. High expression of
      EGFR, c-erbB-2, MMP-2 or -9 was associated with advanced clinical stages, nodal
      metastases and tumor-stages. However, high expression of VEGF or MMP-3 was not
      associated with any clinico-pathologic parameters except significant correlation
      between VEGF and the tumor site. There were significant correlations between
      EGFR, c-erbB-2, MMP-2 and -9 in HNSCC patients. Conversely, no correlation was
      found between VEGF or MMP-3 and the other markers. However, significant
      correlation was found between MMP-3 or -9 and VEGF. The results indicate that the
      expression of EGFR, c-erbB-2, VEGF or MMPs play an important role in tumor
      growth, invasion and metastasis in HNSCC. The authors conclude that EGFR, c-erbB
      2, MMP-2 and -9 could be good independent prognostic markers, but not VEGF and
      MMP-3.

PMID- 15254683
TI  - Thymosin beta-10 gene expression as a possible tool in diagnosis of thyroid
      neoplasias.
AB  - Overexpression of thymosin beta-10 (TB10) has been shown in rat thyroid
      transformed cell lines, and in human thyroid carcinoma tissues and cell lines. To
      investigate whether TB10 detection could be a valid tool in the diagnosis of
      human thyroid neoplasias, we extended the analysis of TB10 expression to a large
      number of thyroid hyperproliferative and neoplastic tissues using an
      immunohistochemical assay. Our analyses showed a TB10 positive staining in all
      human thyroid carcinomas particularly in the anaplastic histotypes, whereas no
      TB10 immunostaining was observed in normal thyroid, in adenomas and the majority
      of the goiters. These results suggest that the evaluation of TB10 gene expression
      may be considered a promising means of diagnosis of human thyroid
      hyperproliferative disorders.

PMID- 15254684
TI  - Nuclear beta-catenin accumulation as a prognostic factor in Dukes' D human
      colorectal cancers.
AB  - Beta-catenin is well recognized to play a crucial role as a transcriptional
      factor during the early step of colorectal carcinogenesis. Some reports
      concerning the clinical implications of cytoplasmic and/or nuclear beta-catenin
      accumulation are available, though their results vary. On the other hand, the
      clinical implication of nuclear accumulation of beta-catenin in Dukes' D
      colorectal cancers (with distant metastasis) has not been investigated. To assess
      its value as a prognostic marker in this stage, we selected the cases with
      synchronous liver metastasis. Thirty-eight surgically resected primary and
      corresponding metastatic liver tumors were examined immunohistochemically and the
      relationships between nuclear beta-catenin accumulation and clinicopathological
      variables were analyzed. Of the 38 primary colorectal cancers analyzed, 11 (29%)
      showed nuclear accumulation of beta-catenin with cytoplasmic staining. Nuclear
      accumulation positivity was more frequently associated with lymph node metastasis
      than being negative [100% (11/11) vs. 67% (18/27), p=0.04]. There was a
      significant difference in median survival time between the nuclear beta-catenin
      positive group (1130 days) and the negative group (2102 days: p=0.037).
      Interestingly, all of the patients (9/9) in the former group had died when the
      recurrence was in the liver, while 42% (8/19) in the latter group had survived
      even if the recurrence was in the liver (p=0.03). In conclusion, though these
      results were obtained in a small series of patients, nuclear accumulation of beta
      catenin may be a useful prognostic marker even in Dukes' D colorectal cancers.

PMID- 15254685
TI  - Cisplatin enhances the p53-independent apoptosis induced by a topoisomerase I
      inhibitor (CPT-11) in the lens epithelial tumors in transgenic mice.
AB  - We reported that CPT-11 could induce apoptosis in mouse lens epithelial tumors
      when it was administered to pregnant alphaT3 mice which developed epithelial cell
      carcinoma in situ in the lens in the perinatal period. p53-deficient alphaT3 mice
      were generated to analyze the influence of p53 status on tumor cells under
      combined chemotherapy. On the 16-18th gestational day, alphaT3 received a single
      i.p. administration of both CPT-11 and Cisplatin, and fetal lens epithelial
      tumors were examined two days later. Apoptosis in the p53-wild-type alphaT3
      tumors was observed in a Cisplatin dose-dependent manner. In addition, it was
      found that Cisplatin augmented CPT-11-induced p53-independent apoptosis in p53
      deficient alphaT3 mice.

PMID- 15254686
TI  - Expression of RCAS1 and its function in human squamous cell carcinoma of the oral
      cavity.
AB  - Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a recently
      discovered human tumor-associated antigen expressed in a wide variety of cancer
      tissues. It has been suggested that tumor cells evade from immune surveillance by
      expression of RCAS1. We investigated whether RCAS1 is expressed in human oral
      squamous cell carcinomas (HOSCCs) or HOSCC (HSC-2, -3, -4, Ca9-22 and KB) cells
      and whether tumor cells expressing RCAS1, induce apoptosis in its receptor
      positive cells, peripheral blood lymphocytes (PBLs). RCAS1 transcripts and
      proteins were detected in five HOSCC cell types. Immunohistochemical examinations
      revealed that RCAS1 was slightly to moderately positive in 32 of 40 cases (80%)
      of HOSCCs. Furthermore, the frequency of RCAS1 expression in HOSCC increased with
      advancing tumor stage according to the pTNM system. Confocal laser microscopy and
      DNA fragmentation assay showed that PBLs, which were stimulated with IL-2,
      underwent apoptosis by co-culturing with KB cells. It was also confirmed by
      Western dot blotting that soluble RCAS1 is secreted into culture supernatants of
      KB cells. The apoptotic tumor-infiltrating lymphocytes (TILs) were detected
      around RCAS1-positive tumor cells in HOSCCs by TUNEL method. These results
      suggest that RCAS1 expression might be associated with progression of oral tumors
      and offer a possible mechanism for oral cancer immune escape.

PMID- 15254687
TI  - Measurement of des-gamma-carboxy prothrombin levels in cancer and non-cancer
      tissue in patients with hepatocellular carcinoma.
AB  - In a recent experiment, we discovered that liver tissue adjacent to HCC can also
      produce des-gamma-carboxy prothrombin (DCP). The goal of this study was to
      advance measurements of DCP levels in hepatocellular carcinoma (HCC) and non
      cancer tissues using an electro-chemiluminescence immunoassay (ECLIA) and
      immunohistochemistry, and to assess their clinical significance. DCP levels in
      HCC tissues ranged from 0.7 to 209862.4 mAU/0.1 g tissue weight, with a median of
      492.6 mAU/0.1 g. DCP levels in non-cancer tissues ranged from 0 to 2329.9 mAU/0.1
      g tissue weight, with a median of 88.8 mAU/0.1 g. DCP levels in cell membranes
      were significantly higher than in the cytoplasm (p<0.001). DCP levels in HCC
      tissue were significantly higher than in non-cancer tissue (p<0.001). The
      logarithm of serum DCP levels correlated not only with that of DCP levels in HCC
      tissues (p=0.019), but also with that in non-cancer tissues (p=0.020), and the
      total DCP level of liver tissues (p=0.016). The logarithm of DCP levels in HCC
      tissues correlated with that of DCP levels in non-cancer tissues (p=0.011). DCP
      levels in HCC tissue with portal vein invasion were significantly greater than in
      HCC tissues without portal vein invasion (p=0.028). DCP levels in non-cancer
      tissues with intrahepatic metastatic lesions were significantly higher than in
      non-cancer tissues without intrahepatic metastatic lesions (p=0.023). Our results
      suggest that the origin of elevated serum DCP may lie not only in HCC tissue, but
      in non-cancer tissue. The existence of HCC may influence production of DCP in non
      cancer tissue. Tissue DCP may be a prognostic factor, while increased DCP levels
      in non-cancer tissues may play an important role in hepatocarcinogenesis.

PMID- 15254688
TI  - Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in
      colorectal cancers.
AB  - Through analysis of genome-wide expression profiles on a cDNA microarray
      consisting of 23,040 human genes, we have been attempting to isolate novel
      molecular targets for diagnosis, treatment and prevention of colorectal carcinoma
      (CRC). Among the genes that were frequently transactivated in colorectal tumors,
      we identified a novel gene termed LEMD1 (LEM domain-containing 1) whose
      expression was elevated in 17 of 18 CRCs compared with their corresponding non
      cancerous mucosae. Northern blotting revealed that LEMD1 was expressed only in
      testis among the 16 normal adult tissues examined. Subsequent analysis identified
      six alternatively spliced forms of the transcript in normal testis, but only one
      of them (656 nucleotides) was expressed in CRCs. Since the LEMD1 protein appears
      to fall in the category of cancer-testis antigens (CTAs), it may represent a
      promising target antigen for immunotherapy of CRCs.

PMID- 15254689
TI  - DFU, a selective COX-2 inhibitor, suppresses MCF-7 xenograft tumor growth in
      mice.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are regarded as potentially important in
      strategies for cancer treatment. however, the precise mechanisms of these anti
      inflammatory drugs as anti-cancer therapy are still unknown. In this study, we
      examined the effect of DFU both in vitro on MCF-7 cell growth, as well as in vivo
      on tumor growth produced by MCF-7 cell injection in mice. DFU has growth
      inhibitory effects on tumor growth in mice compared to the control group. We
      examined the tumor tissues for apoptosis and angiogenesis by immunostaining.
      Apoptosis was detected only in the treatment group. DFU treatment also resulted
      in the inhibition of angiogenesis, as well as decreased COX-2 expression. Results
      of this study suggest that inhibitory effects of DFU might be COX-2 dependent.

PMID- 15254690
TI  - Dysregulation of apoptosis is a major mechanism in the lymph node involvement in
      colorectal carcinoma.
AB  - The purpose of this study was to define gene expression profile changes in
      colorectal tumors in order to identify target genes involved in neoplastic
      progression. cDNA microarray analysis was used to detect differences in gene
      expression profiles between colon tumor samples obtained from 20 patients in
      different tumor stages. Genes included in the cDNA microarray were selected
      according to their role in the cell cycle, apoptosis process, drug resistance and
      transcription factor regulation. Cluster analysis showed 2 well differentiated
      gene expression profiles between colorectal tumors with or without lymph node
      involvement. Some of these genes are important regulators of apoptotic pathways
      (DAD1, APO3, DRAK1 or BIK), suggesting that this process could be associated with
      node involvement. Subsequent analysis of certain genes identified in the
      microarray analysis were confirmed by quantitative real-time PCR. Our data
      suggest that microarray technology could discriminate between the involvement of
      regional lymph node in colon cancer where apoptosis-related genes would be
      implied. This preliminary analysis also suggests that the gene expression profile
      may be useful in improving risk-group stratification.

PMID- 15254692
TI  - Comparative analysis of alpha2,3/2,6-linked N-acetylneuraminic acid and
      cytokeratin expression in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell cancer (HNSCC) requires precise characterization of
      their biological properties to better stratify treatment approaches. Some
      biological features of tumor cells are related to altered glycosylation of their
      surface. This study characterized alpha2,3/6-N-acetylneuraminic acid (NeuNAc)
      expression in adult squamous epithelia of primary and metastatic HNSCC in
      relation to expression of well established differentiation markers, such as
      cytokeratins. The expression of NeuNAc was assessed by plant lectins: Maackia
      amurensis agglutinin type 2 (MAA) and Sambucus nigra agglutinin (SNA) specific
      for alpha2,3NeuNAc and alpha2,6NeuNAc, respectively. Double labeling studies at
      the single-cell level were performed to compare alpha2,3/6NeuNAc linkage with
      expression of intermediate filaments. In studied normal adult epithelia,
      predominantly basal expression of alpha2,6NeuNAc and suprabasal expression of
      alpha2,3NeuNAc was seen, showing their differentiation-dependent linkage. The
      cells with markers of terminal differentiation (i.e. CK10+ alpha2,3NeuNAc+
      alpha2,6NeuNAc-) prevailed in HNSCC, with increasing proportion from
      differentiation grade G1 to G3. High proportions of cytokeratin pCK37+ carcinoma
      cells occurred in all studied tumors and were accompanied by a hypersialylated
      phenotype (i.e. alpha2,3 NeuNAc+ alpha2,6NeuNAc+) not generally seen in non
      transformed epithelia. It is hypothesized that these cells could be the pool for
      tumor spreading in the organism. Monitoring HNSCC using multiparameter phenotype
      analysis can produce new data important for the understanding of the biological
      behavior of HNSCC, and useful for the treatment rationalization.

PMID- 15254691
TI  - Constitutive activation of Stat3 correlates with increased expression of the c
      Met/HGF receptor in oral squamous cell carcinoma.
AB  - Stat3 belongs to a family of signal transducers and activators of transcription.
      Constitutive activation of Stat3 has been observed in many human malignancies. In
      addition, mutated Stat3 has been shown to possess oncogenic potential on its own,
      and activation of Stat3 signaling is required for HGF/c-Met-mediated
      tumorigenesis. In this study, we examined the correlation between Stat3
      activation and HGF/c-Met signaling in samples of oral squamous cell carcinoma
      (OSCC). Immunohistochemical examination revealed the phosphorylated form of Stat3
      in the nuclei of 62/84 OSCC tissue samples but not in normal mucosa, while c-Met
      expression was detected in 48 samples. Approximately half of the c-Met positive
      samples also contained phospho-Stat3. There were highly significant correlations
      between activation of Stat3 and c-Met expression (p=0.00097) and tumor stage.
      These results indicate that activation of Stat3 mediated by c-Met is frequently
      associated with the progression of OSCC.

PMID- 15254693
TI  - Predicting the recurrence/metastasis of stage II and III breast cancer with lymph
      node metastasis.
AB  - This study compared prediction of the recurrence of breast cancer by detection of
      occult neoplastic cells (ONCs) in lymph nodes or by using the criteria for a high
      risk of recurrence and metastasis of gastric/large bowel cancer. The subjects
      were 45 patients with stage II and III node-positive breast cancer. Prediction of
      recurrence by detection of ONCs showed a sensitivity of 78.6% (11/14), a false
      negative rate of 21.4% (3/14), a specificity of 96.4% (30/31), a false-positive
      rate of 3.2% (1/31), and an accuracy of 87.7% in patients with stage II and III
      node-positive cancer. Prediction of recurrence based on positivity for at least 2
      of the high-risk criteria showed a sensitivity of 92.9% (13/14), a false-negative
      rate of 7.1% (1/14), a specificity of 87.1% (27/31), a false-positive rate of
      12.9% (4/31), and an accuracy of 90.0% in patients with stage II and III node
      positive cancer. These results suggest that ONCs plus the high-risk criteria are
      useful for predicting recurrence/metastasis of stage II and III node-positive
      breast cancer during the early postoperative period with a high sensitivity and
      accuracy.

PMID- 15254694
TI  - Usefulness of collagen gel droplet embedded culture drug sensitivity testing in
      ovarian cancer.
AB  - Due to the emergence of new anticancer agents for the treatment of ovarian
      cancer, methods to determine which agents will be most effective in individual
      patients are required. In order to investigate the potential for tailor-made
      chemotherapy, the drug sensitivities of various ovarian cancers were examined
      using collagen gel droplet embedded culture drug sensitivity testing (CD-DST),
      and the results were correlated with clinical outcomes. Sensitivities to
      paclitaxel, cisplatin, doxorubicin, etoposide, and SN-38, which is an active
      metabolite of irinotecan, were examined. Eight out of 22 samples failed to grow
      colonies and thus, their cell sensitivities could not be determined. Out of the
      14 cases from which CD-DST results were obtained, seven patients then received
      chemotherapy aimed at inducing remission, while four received adjuvant, and three
      did not receive any chemotherapy. Three of the four tumors subsequently treated
      with adjuvant chemotherapy showed sensitivity to TXL and CDDP on CD-DST analysis,
      while one did not. None of these patients experienced recurrent disease from 24
      to 36 months. Five of the seven tumors subsequently treated with chemotherapy
      aimed at inducing remission showed sensitivity to the relevant anticancer agents
      upon CD-DST analysis, while two did not. Among the five cases that showed tumor
      cell sensitivity, three experienced complete responses, one achieved a partial
      response and one had progressive disease. For the remaining two cases that
      demonstrated tumor cell resistance, one had stable disease and one had
      progressive disease following chemotherapy. Thus, six out of the seven cases
      (85.7%) that received chemotherapy aimed at inducing remission had clinical
      outcomes in keeping with the results of CD-DST. In conclusion, CD-DST results
      reflect clinical outcomes and may be a useful means by which to select drugs to
      which ovarian cancer cells are chemosensitive.

PMID- 15254695
TI  - BRCA2 germline mutations in primary cancer of the fallopian tube.
AB  - Germline mutations of BRCA1 and BRCA2 genes confer susceptibility to breast and
      ovarian cancer. It has been recently reported that BRCA1/2 mutations may also
      predispose to fallopian tube cancer. We report the presence of germline BRCA2
      gene mutations in three out of four subjects with fallopian tube cancer diagnosed
      in a two-year time span at our clinic. The mothers of two of these women suffered
      from breast or ovarian carcinoma. These results suggest on one hand that in
      patients with a history suggestive for a heredofamilial breast/ovarian cancer
      syndrome fallopian tube carcinoma is associated with high risk of BRCA2 mutation,
      and on the other hand that in patients/individuals with germline BRCA2 gene
      mutations in whom a prophylactic oophorectomy is performed, removal of fallopian
      tubes may be considered.

PMID- 15254696
TI  - Establishment of a new scirrhous gastric carcinoma cell line with microsatellite
      instability.
AB  - We report on the establishment of a new scirrhous gastric cancer cell line with
      microsatellite instability (MSI), designated OCUM-7. This cell line was derived
      from a primary scirrhous gastric carcinoma. The cells were floating and round
      shape in culture. Histologic findings of xenografted tumor obtained from OCUM-7
      cells showed a poorly differentiated adenocarcinoma with medullary growth. DNA
      histograms of OCUM-7 cells showed an aneuploid pattern. MSI status of OCUM-7 was
      analyzed using 8 microsatellite markers. Five of 8 microsatellite loci showed a
      novel band shift, which demonstrated that OCUM-7 cells were MSI-high. MSI
      positive cell lines established from a primary scirrhous gastric carcinoma have
      not been reported, while several reports of the establishment of a scirrhous
      gastric cancer cell line are available. OCUM-7 might be beneficial for analyzing
      the mechanisms of MSI in scirrhous gastric carcinoma.

PMID- 15254697
TI  - Mobilization of peripheral blood stem cells (PBSCs) after etoposide, adriamycin
      and cisplatin therapy, and a multimodal cell therapy approach with PBSCs in
      advanced gastric cancer.
AB  - The EAP combination of etoposide (ETP), doxorubicin (ADM) and cisplatin (CDDP)
      has been reported to be highly active for advanced gastric cancer. However, it is
      associated with severe myelotoxicity, and its use has declined. We examined
      whether peripheral blood stem cells (PBSCs) could be mobilized during
      hematopoietic recovery after EAP, and assessed the possibility of using
      multimodal cell therapy with PBSCs for the treatment of advanced gastric cancer.
      Five men with advanced gastric adenocarcinoma were enrolled. All patients were
      chemotherapy-naive. EAP (ETP, 360 mg/m2; ADM, 40 mg/m2; CDDP, 80 mg/m2) was given
      to each patient, and myelotoxicity was carefully monitored. Granulocyte colony
      stimulating factor was administered after the neutrophil nadir, and PBSCs were
      collected by leukapheresis during hematopoietic recovery. The median nadir of the
      neutrophil count after EAP was 225/ml, occurring between day 17 and 20.
      Sufficient numbers of PBSCs [CD34(+) cells, CFU-GM] could be mobilized in 4/5
      patients. A 45-year-old patient with extended lymph node metastasis received high
      dose EAP with peripheral blood stem cell transplantation (PBSCT), followed by
      cancer vaccine therapy with dendritic cells (DCs), induced from cryopreserved
      PBSCs. Both high-dose EAP with PBSCT and DC-based immunotherapy was safely
      performed for the first time against gastric cancer. Although associated with
      severe myelotoxicity, EAP can mobilize sufficient numbers of PBSCs during
      hematopoietic recovery. Multimodal cell therapy combining high-dose chemotherapy
      with PBSCT and DC-based immunotherapy is feasible and can be a reasonable
      approach in advanced gastric cancer.

PMID- 15254698
TI  - Frequent loss of heterozygosity on chromosome 10p14-p15 in esophageal dysplasia
      and squamous cell carcinoma.
AB  - High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have
      been reported in various tumors, including glioma, pulmonary carcinoid and
      cervical, hepatic and prostatic carcinomas. These findings suggest the presence
      of a tumor suppressor gene at the loci. However, analysis of LOH on chromosome
      10p14-p15 in esophageal tumors has not been reported. Therefore, we examined LOH
      on chromosome 10p14-p15 in 88 esophageal squamous cell carcinomas (SCC) (35
      superficial- and 53 advanced-types) and 44 dysplasias by microsatellite assay.
      Five oligonucleotide primer sets for microsatellite loci D10S191, D10S501,
      D10S559, D10S558 and D10S249 were used. In dysplasias, frequent LOH was detected
      with markers D10S191 (26%) and D10S249 (33%). In superficial esophageal SCCs,
      frequent LOH was detected with markers D10S191 (26%), D10S559 (50%), D10S558
      (29%) and D10S249 (33%). In advanced esophageal SCCs, we found frequent LOH was
      detected with markers D10S191 (38%), D10S501 (25%) and D10S559 (30%). There were
      no significant correlations between LOH on chromosome 10p14-p15 and
      clinicopathologic features, including patient age, sex, tumor location, depth of
      invasion and lymph node metastasis. These data suggest that a putative tumor
      suppressor gene for esophageal carcinogenesis may be located on chromosome 10p14
      p15 and that malfunction of this gene may be involved in the development but not
      progression of esophageal tumors.

PMID- 15254699
TI  - Influence of CpG island methylation status in O6-methylguanine-DNA
      methyltransferase expression of oral cancer cell lines.
AB  - It is known that the O6-methylguanine-DNA methyltransferase (MGMT) gene is
      susceptible to epigenetic regulation associated with an altered frequency of CpG
      methylation. To investigate whether epigenetic regulation of the MGMT gene might
      lead to significant reductions in the expression levels of cancer cells, we
      sought evidence of a link between the methylation status of the MGMT promoter and
      the expression levels of seven human oral cancer cell lines. We found two
      frequently methylated regions: the 5' region extending from nt 690 to nt 893 in
      the promoter, and the more 3' region extending from nt 1060 to nt 1151 in the
      untranslated first exon. The 3' region was hypermethylated independently of MGMT
      expression levels in all cell lines. By contrast, in the three MGMT-downregulated
      cell lines (SAS, Hep2, HO-1-u-1), the levels of MGMT expression were inversely
      related to the density of 5' region of the methylated CpGs in the MGMT promoter.
      Our results implied that the transcriptional inactivation of MGMT might require
      methylation of the 5' region, but not that of the 3' region in oral cancer cell
      lines. We further explored the role of methylation in MGMT expression by treating
      cells with 5-Aza-2'-deoxycytidine (5Aza-dC). 5Aza-dC treatment led to the partial
      or complete cytosine demethylation of two frequently methylated MGMT regions in
      all cell lines. 5Aza-dC succeeded in upregulating of the MGMT mRNA levels in only
      2 of 7 cell lines (HSC3 and HO-1-u-1), and in fact reduced MGMT mRNA in the other
      5 cell lines. Furthermore, 5Aza-dC had an inhibitory effect on MGMT protein
      levels in all cell lines. Our results suggest that MGMT levels may not revert
      after 5Aza-dC treatment. Based on our findings, the regulation of MGMT expression
      appears to be more complex than previously thought, although it is at least
      partially influenced by CpG methylation. Accordingly, care should be taken
      interpreting the link between MGMT methylation and expression.

PMID- 15254700
TI  - Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in
      hepatocellular carcinoma and metastatic liver cancer.
AB  - Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are
      considered to be key enzymes affecting the prognosis for patients with various
      cancers. We tried to prove the correlation of TP and DPD expression in
      hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD
      levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and
      adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis
      patients together with 9 of their primary cancers. TP levels were higher in the
      primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP
      levels were higher in HCC than in liver metastasis, and TP levels in the adjacent
      tissues of HCC were also higher than those in adjacent tissues of liver
      metastasis. TP levels were higher in liver metastasis than in primary cancer, and
      TP levels in adjacent tissues of liver metastasis were also higher than those in
      adjacent tissues of primary cancer. However, there were no differences in TP T/N
      ratio between HCC and liver metastasis, and between primary cancer and liver
      metastasis. DPD levels were lower in the liver metastasis compared with the
      adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver
      tissues were higher than those in primary cancer or its adjacent tissues. There
      were no differences in DPD T/N ratio between HCC and liver metastasis, and
      between primary cancer and liver metastasis. Thus, we demonstrated that TP was
      highly expressed in liver malignancy. We may be able to increase the success of
      anticancer chemotherapy for liver malignancy while decreasing the side effects by
      analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.

PMID- 15254701
TI  - Phosphatidylcholine and cholesteryl esters identify the infiltrating behaviour of
      a clear cell renal carcinoma: 1H, 13C and 31P MRS evidence.
AB  - This study presents a multinuclear (1H, 13C and 31P) magnetic resonance
      spectroscopy characterization of the total lipid fraction extracted from
      different regions of a human kidney affected by a clear cell renal carcinoma. It
      was thus possible to demonstrate that cholesteryl esters and phosphatidylcholine
      are markers of the tumor infiltration, histologically confirmed, in the kidney
      medulla. The tumor tissue contains twice the amount of phosphatidylcholine
      compared to normal cortex. The results appear relevant in light of new clinical
      applications based on the biochemical composition of human tissues.

PMID- 15254702
TI  - p53 dependence and apoptosis in response to FP treatment with p53-transfected
      colon cancer cell lines by use of thin layer collagen gel.
AB  - The combination of 5-fluorouracil (5-FU) plus Cisplatin (CDDP) (FP treatment)
      possesses synergistic cytotoxicity against colon cancer. The molecular mechanisms
      by which chemotherapeutic agents induce apoptosis have been clarified by
      identifying apoptosis-related genes such p53 and bcl-2. We previously established
      a new experimental technique in which cancer cells are distributed in thin
      collagen gel as 1 or 2 cell layers. additionally, we evaluated the efficacy and
      toxicity of FP treatment in the gastric and colon cancer cell lines, and examined
      the relationship between the response to FP treatment and apoptosis. In these
      results we reported transfection of normal p53 gene into p53 mutant and analyzed
      the impact of the p53 gene in a sensitivity test. In this study, we examined
      induced apoptosis in colon cancer cell lines and the status of p53 expression in
      response to treatment of HCT116, COLO320, SW480 and DLD1 with 5-FU alone, CDDP
      alone and FP treatment under flow cytometric analysis. Transfection of SW480 and
      DLD1 cells was performed to compare the chemosensitivity of naturally occurring
      mutant-type p53 SW480 and DLD1 cells with neo-transfected SW480 and DLD1 cells
      and transfected SW480 and DLD1 cells. Appreciable apoptosis was induced in HCT116
      and COLO320 (p53 wild-type) but not in SW480 and DLD1 cells (p53 mutant-type).
      Transfected SW480 and DLD1 cells underwent significantly more apoptosis
      (p<lt;0.001) than naturally occurring mutant-type p53 SW480 and DLD1 cells. p53
      expression may further induce apoptosis in FP treatment. Patients with p53 wild
      type may be better candidates for FP therapy than patients with p53 mutant-type
      in colon cancer. Therefore, we think that p53 may be also effective against colon
      cancer in FP therapy.

PMID- 15254703
TI  - The analysis of pyridylamino-dextran sulfate oligomers by high-performance liquid
      chromatography and a novel detection system for sulfated polysaccharides.
AB  - Dextran sulfate sodium (DSS) is a strong negatively charged heparin-like
      polysaccharide and has anti-immunodeficiency virus, anti-carcinogenesis, or
      occasionally tumor-promotion effects. The biological metabolism of DSS, however,
      remains unclear. In a previous study, we reported a novel method for the
      separation and quantification of DSS, using fluorometric labeling with 2
      aminopyridine and a combination of size-exclusion and reverse phase high
      performance liquid chromatography. In the present study, we have applied this
      method for analyses of in vitro chemical or enzymatic depolymerization of
      pyridylamino-DSS (PA-DSS). PA-DSS was depolymerized by specific enzymes such as
      alpha-amylase and alpha-glycosidase, but not by dextranase or heparinase. Unknown
      enzymes derived from cultured intestinal cells also strongly depolymerized PA-DSS
      as did alkaline substances. On the other hand, we have established a novel
      detection system using a post-column reaction. This method utilizes the
      spectrophotometrically metachromatic reaction of toluidine blue solution with
      DSS. This novel detection system may be specific and may potentially provide
      useful information in the analyses of sulfated polysaccharides, which are present
      in environmental and biological materials.

PMID- 15254704
TI  - Effect of extracorporal high hydrostatic pressure on tumor cell adherence and
      viability.
AB  - In orthopedic surgery, reconstruction of bone segments afflicted with cancer is
      done in various ways, including devitalization of the bone or replacement of the
      bone by artificial bone constructs. To devitalize bone cells, extracorporal
      irradiation or autoclaving is used although both methods have substantial
      disadvantages. We now introduce the technique of extracorporal high hydrostatic
      pressure (HHP) treatment to disintegrate tumor cells in suspension or in their
      adherent state. The effect of HHP on cell viability, adherence and morphology of
      four different tumor cell lines (fibrosarcoma HT-1080, osteosarcoma SAOS-2,
      ovarian cancer OV-MZ-6, breast cancer MCF-7) was investigated. For this,
      adherently growing (with fibronectin serving as the growth-promoting substrate)
      or suspended tumor cells were placed into a test vial which was transferred into
      the pressure chamber of a high hydrostatic pressure device. After pressure
      treatment, the pressure was relaxed to atmospheric pressure and subsequently cell
      viability, adherence and morphology assessed. High hydrostatic pressure as high
      as 350 MPa (10 min, 37 degrees C) did not detach the tumor cells from the
      fibronectin-coated surface although at these conditions all of the four cell
      lines tested were irreversibly damaged. Adherently growing tumor cells were
      considerably more sensitive to HHP than tumor cells detached from the surface and
      treated by HHP in suspension. HHP-treated tumor cells showed drastic
      morphological changes, evident by cell membrane ruffling and bleb formation. At
      150 MPa adherently growing or suspended tumor cells are irreversibly damaged by
      short-term treatment with HHP. In another investigation, we experienced that
      treatment of freshly excised bones or tendons by HHP has no adverse effect on
      their stability or biomechanical properties. Therefore, we anticipate that in
      orthopedic surgery HHP could be used as a new gentle way of treating resected
      cancer-afflicted bones or tendons to inactivate tumor cells before autologous
      reimplantation.

PMID- 15254705
TI  - Eradication of HPV post-surgical treatments, its correlation with specific types,
      types of surgery and the physical status.
AB  - Low-risk human papillomaviruses (HPVs) will be completely eradicated as long as
      most visible lesions are treated. However, it is uncertain whether this is also
      the case for high-risk HPVs that are capable of causing cervical cancer. Many
      recent studies have demonstrated a high incidence of HPV persistence during post
      conization or loop electrosurgical excision (LEEP) due to high-grade cervical
      intraepithelial neoplasia (CIN). In this report, we correlated the post-operative
      HPV status with pre-operative HPV type, types of surgery and HPV's physical
      status. Post-operative HPV E6 amplification by nested PCR was carried out for 157
      female patients with positive pre-operative HPV. They underwent LEEPs,
      therapeutic laser conizations, and simple or radical hysterectomies. We found
      that high-risk types of HPVs were eradicated in 26.4% (42/159) of patients after
      extirpation of the lesions. The clearance rate of HPVs increased to 39.2%
      (40/102), excluding patients with other high-risk (OHR) kinds of type 31, 52b and
      58, since OHR persisted after almost all surgeries. Eradication of HPV after
      radical hysterectomies are highly expected for patients with invasive cancer
      (70.0%, when excluding OHR), while more than half of them with CIN continue to
      carry pre-operative types of HPV or some different types from before treatment.
      Type 33 is most frequently persistent among types 16, 18 and 33. Persistent high
      risk HPVs increase the risk for recurrence of post-surgical treatments of CIN,
      but the incidence is not high as long as the lesion is completely removed.

PMID- 15254706
TI  - High expression of two genes selected by iAFLP: a new prognostic factor of
      estrogen receptor-positive breast cancer.
AB  - To detect patients with poor prognosis among those with estrogen receptor (ER)
      positive breast cancer, who generally show good prognosis, we analyzed gene
      expression profiles of 35 ER-positive tumors by using a high through-put RT-PCR
      technique, iAFLP. High expression of six genes out of 7,508 was related to poor
      prognosis in this group. From these six genes, NFE2L2 and TIAL1 were selected as
      genes associated with poor prognosis by means of a validation study with another
      set of 56 ER-positive breast cancers. High expression of these two genes was
      determined to be significantly predictive for poor prognosis of patients with ER
      positive breast cancer, and may help to achieve optimal selection of adjuvant
      treatment for such patients.

PMID- 15254707
TI  - Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A
      methylation in non-small cell lung cancer: potential prognostic implication.
AB  - E-cadherin gene is often termed a 'metastasis suppressor' gene and inactivation
      of this gene through promoter methylation occurs in various epithelial cancer.
      This study assessed the methylation status of p16INK4a and E-cadherin genes,
      correlated with clinical characteristics in lung cancer patients. Forty-five
      patients with non-small cell lung cancer (NSCLC) were evaluated for methylation
      status of p16INK4a and E-cadherin genes by using the methylation-specific PCR. E
      cadherin expression in tumor samples was examined by immunohistochemistry.
      Overall duration of survival in different subsets of NSCLC with or without
      p16INK4a or E-cad methylation at diagnosis was compared by using the Kaplan-Meier
      method and log-rank test. We found the hypermethylation of p16INK4a gene in 38%
      (17/45) of our subjects. While the E-cadherin gene was hypermethylated in 62%
      (28/45) related with reduced E-cadherin expression, and methylation status of
      both p16INK4a and E-cadherin genes seemed to be independent. Seventy-six percent
      (34/45) of NSCLC patients had an abnormal methylation pattern in at least one
      gene. Although there was no difference in overall survival of patients between
      methylated p16INK4a and unmethylated p16INK4a, NSCLS patients with
      hypermethylation of both genes (concordant pattern) had a significantly good
      prognosis. In contrast, NSCLC patients with hypermethylated p16INK4a but un
      methylated E-cadherin gene (discordant pattern) had a significantly poor
      prognosis. E-cadherin and p16INK4a are commonly methylated in NSCLC and the
      methylation pattern of p16INK4a and E-cadherin genes may have prognostic value
      for the outcome of NSCLC patients.

PMID- 15254708
TI  - Confocal endomicroscopic imaging of normal and neoplastic human tongue tissue
      using ALA-induced-PPIX fluorescence: a preliminary study.
AB  - Confocal endomicroscopy is a novel and non-invasive microscopic technique that
      enables surface and subsurface imaging of living tissues or cells in vivo. The
      purpose of this study was to assess the possibility of utilizing a rigid confocal
      endomicroscope (RCE) system developed for detecting morphological changes in
      living normal and neoplastic human tongue tissue in combination with 5
      aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX (PPIX)
      fluorescence. Three patients with squamous cell carcinoma (SCC) of the tongue
      were examined using the novel RCE system with the excitation wavelength at 488 nm
      from an argon-ion laser and the detection wavelengths of the tissue fluorescence
      above 515 nm. Patients were topically applied with 0.4% of 5-ALA rinsing solution
      to the oral mucosa for approximately 15 min, and then the confocal
      endomicroscopic imaging of tissue PPIX fluorescence was performed on the lesion
      sites of the tongue after an optimal incubation period of 90-120 min. For
      comparison purposes, ALA-PPIX fluorescence confocal endomicroscopic imaging was
      also carried out on the normal sites of the tongue in vivo from two healthy
      volunteers. Image distortions due to tissue motion can be minimized using a
      specially designed tissue stabilizer attached to the RCE probe. Good quality ALA
      mediated confocal fluorescence images of the tongue can be acquired in real-time,
      providing well-defined micro-morphological structures (e.g., filiform papillae,
      keratinized epithelium and fungiform papillae) of the tongue in vivo. Changes of
      tissue structures in oral tissue associated with cancer transformation can also
      be clearly identified using the RCE imaging. Preliminary results obtained in this
      study suggest that ALA-mediated rigid confocal endomicroscopy may have a
      significant potential for the rapid, non-invasive diagnosis and evaluation of
      early oral cancers in vivo.

PMID- 15254709
TI  - Overexpression of cyclooxygenase-2 in childhood ependymomas: role of COX-2
      inhibitor in growth and multi-drug resistance in vitro.
AB  - The management of ependymomas remains one of the most frustrating issues in
      pediatric neuro-oncology. Gross total resection is not always possible, and
      intensive chemotherapy and craniospinal radiotherapy have made no clear advances.
      Moreover, the chemoresistance of ependymomas may be explained by the expression
      of membrane transport molecule P-glycoprotein (P-gp). In this study the
      expression of cyclooxygenase 2 (COX-2) and the role of the specific COX-2
      inhibitor NS-398 in growth and multi-drug resistance of ependymomas were
      investigated. COX-2 protein expression was assessed in 19 ependymomas
      immunohistochemically, and the effect of NS-398 on growth and multi-drug
      resistance was investigated using two primary cultured ependymoma cell lines. COX
      2 protein expression was observed in 15 (79%) of the 19 ependymomas. NS-398 was
      found to reduce the proliferation of monolayer cell cultures in a dose- and time
      dependent manner and to induce apoptosis and lower bcl-2 protein levels. After NS
      398 treatment, Western blotting showed reduced P-gp expression and a rhodamine
      123 efflux assay demonstrated a significant decrease in P-gp activity. Our
      findings demonstrate that COX-2 is overexpressed in ependymomas and that NS-398
      is able to induce apoptosis and suppress P-gp expression and activity.

PMID- 15254710
TI  - Inhibition of tumor-associated fatty acid synthase activity enhances vinorelbine
      (Navelbine)-induced cytotoxicity and apoptotic cell death in human breast cancer
      cells.
AB  - The lipogenic enzyme fatty acid synthase (FAS) is differentially overexpressed
      and hyperactivated in a biologically aggressive subset of breast carcinomas and
      minimally in most normal adult tissues, rendering it an interesting target for
      anti-neoplastic therapy development. Current trends in the treatment of human
      breast cancer are with drug combinations that result in improved responses as
      well as the ability to use less toxic concentrations of the drugs. Here, we
      envisioned that combinations of conventional chemotherapeutic agents with novel
      compounds directed against breast cancer-associated FAS hyperactivity may provide
      increased efficacy over existing therapy for human breast cancer. Specifically,
      we examined the ability of the mycotoxin cerulenin, a potent and non-competitive
      inhibitor of FAS activity, to enhance the cytotoxic effects of vinorelbine
      (Navelbine), a derivative of vinca alkaloid that interferes with tubulin assembly
      and exhibits activity against metastatic breast cancer. SK-Br3, MCF-7 and MDA-MB
      231 human breast cancer cell lines were employed as models of high, moderate and
      low levels of FAS ('cerulenin-target'), respectively. Combinations of cerulenin
      with vinorelbine were tested for synergism, additivity or antagonism using the
      isobologram and the median-effect plot (Chou-Talalay) analyses. Breast cancer
      cells were either simultaneously exposed to cerulenin and vinorelbine for 24 h or
      sequentially to cerulenin for 24 h followed by vinorelbine for 24 h. Concurrent
      exposure to cerulenin and vinorelbine resulted in synergistic interactions in MCF
      7 and MDA-MB-231 cell lines, while additivity was found in SK-Br3 cells.
      Sequencing cerulenin followed by vinorelbine resulted in synergism for SK-Br3 and
      MDA-MB-231 cells, whereas it showed additive effects in MCF-7 cells. FAS activity
      blockade was found to synergistically enhance apoptosis-inducing activity of
      vinorelbine, as determined by an enzyme-linked immunosorbent assay for histone
      associated DNA fragments. To the best of our knowledge this is the first study
      demonstrating that breast cancer-associated FAS is playing an active role in
      human breast cancer chemosensitivity. We suggest that pharmacological inhibition
      of FAS activity is a novel molecular approach to enhance the cytotoxic effects of
      existing chemotherapeutic agents in human breast cancer.

PMID- 15254711
TI  - Identification and characterization of human CKTSF1B2 and CKTSF1B3 genes in
      silico.
AB  - Bone morphogenetic proteins (BMPs) are implicated in the regulation of
      morphogenesis and proliferation during embryogenesis and carcinogenesis. We have
      previously reported over-expression of BMP4 in diffuse-type gastric cancer cells.
      BMP signaling is regulated by tissue-specific expression of ligands and receptors
      as well as by secreted-type antagonists, such as CKTSF1B1 (Gremlin), CER1
      (Cerberus 1), Noggin, SOSTDC1 (Ectodin), and Chordin. Here, we identified two
      novel genes related to CKTSF1B1 and CER1 by using bioinformatics. Two novel
      members of human CKTSF1B gene family were designated CKTSF1B2 (GREM2 or PRDC) and
      CKTSF1B3 (GREM3 or DANTE). FLJ21195 (BC046632.1) was the representative human
      CKTSF1B2 cDNA, and CKTSF1B2 gene was mapped to human chromosome 1q43. Human
      CKTSF1B2 showed 94.0% total amino-acid identity with mouse Cktsf1b2 (Prdc).
      FLJ38607 (AK095926.1) was the representative human CKTSF1B3 cDNA, and CKTSF1B3
      gene was mapped to human chromosome 19p13.2. Human CKTSF1B3 showed 61.9% total
      amino-acid identity with mouse Cktsf1b2 (Dante). N-terminal signal peptide and
      DAN domain with nine cysteine residues were conserved among CKTSF1B1, CKTSF1B2,
      CKTSF1B3 and CER1. Phylogenetic analyses revealed that CKTSF1B2 was more related
      to CKTSF1B1, and that CKTSF1B3 was more related to CER1. CKTSF1B1, CKTSF1B2,
      CKTSF1B3 and CER1 constitute the CKTSF1B family among secreted-type cysteine knot
      superfamily proteins. This is the first report on identification and
      characterization of the human CKTSF1B2 and CKTSF1B3 genes.

PMID- 15254712
TI  - Identification and characterization of human TMEM25 and mouse Tmem25 genes in
      silico.
AB  - Immunoglobulin superfamily members are implicated in immune responses, growth
      factor signaling, and cell adhesion. IGSF4 (IGSF4A), homologous to IGSF4B,
      IGSF4C, IGSF4D, PVR, PVRL1, PVRL2, PVRL3 and PVRL4, is down-regulated in lung
      cancer. IGSF11, homologous to CXADR (CAR), ESAM and ASAM, is up-regulated in the
      intestinal-type gastric cancer. Here, we identified and characterized a novel
      member of the immunoglobulin superfamily, TMEM25, by using bioinformatics.
      BC042896 and AY358919 cDNAs were derived from human TMEM25 gene, while AK002841
      cDNA was derived from mouse Tmem25 gene. TMEM25 isoform 1 (BC042896), consisting
      of exons 1-9, encoded a 366-aa transmembrane protein. TMEM25 isoform 2
      (AY358919), consisting of exons 1-4 and 6-9, encoded a 322-aa secreted protein.
      Human TMEM25 gene was found to encode transmembrane-type as well as secreted-type
      proteins due to alternative splicing of exon-skipping type. TMEM25 mRNA was
      expressed in brain, including cerebellar cortex and hippocampus, as well as in
      neuroblastoma, brain tumors, and gastric cancer. Human TMEM25 isoform 1 showed
      91.0% total-amino-acid identity with mouse Tmem25. TMEM25 was identified as a
      member of immunoglobulin superfamily, because codon 42-112 of TMEM25 was the C-2
      type immunoglobulin domain homologous to Hemicentin (Fibulin-6, FIBL6), Titin
      (TTN), Sialoadhesin (SN) and Nephrin (NEPHS1). Human TMEM25 gene was located at
      the 11q23.3 oncogenomic recombination hotspot around the MLL amplicon and the
      neuroblastoma deleted region. TMEM25 is a target of pharmacogenomics in the field
      of oncology and regenerative medicine.

PMID- 15254713
TI  - CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T
      lymphocytes to target HCC cells with shared tumor antigens.
AB  - Human HCC cell lines (BEL-7402, SMMC-7721 and QGY-7703) do not express CD80
      molecules, although they express MHC class I molecules and ICAM-1. HCC's poor
      immunogenicity may therefore be due to lack of CD80 molecules. This study first
      investigated whether CD80 molecules could provide minimal co-stimulatory signal
      for establishing an efficient anti-tumor immunity in HCC and second, whether the
      transfection of CD80 into the BEL-7402 cell line could induce T cell activation
      for targeting other HCC cell lines expressing shared common antigens. The
      transfection of cDNA encoding CD80 into ICAM-1+ HCC BEL-7402 cells was confirmed
      by flow cytometrical analysis. The CD80-transfected cells could enhance the
      immunogenicity of BEL-7402 cells as detected by T cell proliferation assay, and
      also activated the T cells at a higher proliferation rate comparing with the BEL
      7402 cells transfected with vector only. The CD80-transfected cell line was also
      found able to activate T cells which subsequently induced cell lysis of SMMC
      7721, QGY-7703 and parent BEL-7402 cell lines as detected by cytotoxicity assay.
      It can be concluded that the cytotoxicity was due to MHC class I restricted CD8+
      cytotoxic T lymphocytes, but not natural killer (NK) cells, since this cytotoxic
      effect could be blocked by anti-MHC class I antibody and the cytotoxicity was
      shown very low in NK-cell-sensitive K562 cell line. Electroporation of CD80 cDNA
      into human HCC cells could increase the expression of the functional CD80
      molecules and enhance the immunogenicity of the genetically-modified HCC cells to
      activate T cells for targeting 3 HCC cell lines in an HLA-restricted manner.

PMID- 15254714
TI  - Adenovirus-mediated HSV-TK gene therapy using the human telomerase promoter
      induced apoptosis of small cell lung cancer cell line.
AB  - Telomerase is a ribonucleoprotein complex the function of which is to add
      telomeric repeats (TTAGGG)n to chromosomal ends, and it is known to play an
      important role in cellular immortalization. Telomerase is highly active in most
      tumor cells, but not in normal cells. As such, it may have possible applications
      in cancer gene therapy. Telomerase consists of two essential components,
      telomerase RNA template (hTR) and catalytic subunit (hTERT). hTERT is expressed
      only in cells and tissues positive for telomerase activity, i.e., tumor and fetal
      cells. We tested the possibility of the utilization of the hTERT promoter in
      targeted cancer gene therapy. We cloned the hTERT promoter in the place of the
      CMV promoter and sub-cloned HSV-TK gene to be controlled by hTERT gene promoter
      in adenovirus shuttle plasmid. Then we constructed recombinant adenovirus Ad-hT
      TK, and infected them into a normal and a small cell lung cancer cell line.
      Through these experiments, we identified the selective tumor specific cell death
      by Ad-hT-TK. Furthermore, cell death detection ELISA and FACS analysis suggest
      that the reduced viability is mediated through the induction of apoptosis,
      indicating that this approach may be a useful method for suppressing cancer
      growth in targeted cancer gene therapy. These results show that Ad-hT-TK could be
      used for SCLC gene therapy.

PMID- 15254715
TI  - Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer
      of esophagus and gastric cardia in China, induced benign and malignant tumors in
      mice.
AB  - This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing
      at high levels in dietary food in high-risk areas of cancer of esophagus and
      gastric cardia in China induced benign and malignant tumors in mice. The levels
      of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using
      high performance liquid chromatography (HPLC) in a total of 97 samples of dietary
      wheat flour, barley and corn collected from families in two areas with high
      mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian,
      Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON
      in three dietary foods was 830+/-927 microg/kg (range 584-1,780 microg/kg) and
      4,281+/-6,114 microg/kg (range 732-10,980 microg/kg) respectively. The highest
      mean level of NIV was 1,780+/-1,705 microg/kg found in barley from Linxian, that
      of DON was 10,980+/-10,139 microg/kg found in corn from Cixiang. NIV was
      undetectable in 2 samples of rice from USA. The mean levels of NIV in three main
      dietary foods in those two high-risk areas were estimated at 400 to 800-fold
      higher than that in the USA, where NIV was undetectable in dietary food, and the
      mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA,
      (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian
      and Cixiang peasants who consumed a diet with high NIV had significantly higher
      risk for developing esophageal cancer than the US residents who consumed food
      without or with negligible amounts of NIV. Three repeated experiments were
      performed using Balb/C mice with inter-mittent application of NIV, alternate with
      12-Tetradeconoyl-phorbol-13-acetate (TPA) application on skin. Papillomas and
      carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of
      experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No
      tumors were found in the 60 control mice applying either TPA or acetone (solvent)
      only on skin.

PMID- 15254716
TI  - UGT1A1*28 polymorphism in ovarian cancer patients.
AB  - (Uridino-diphosphate)glucuronosyl-transferase enzyme 1A1 isoform (UGT1A1) is
      involved in glucuronidation of antineoplastic drugs such as SN38, the active
      metabolite of irinotecan, as well as estrogens and their metabolites. UGT1A1*28
      polymorphism decreases UGT1A1 expression and could alter estrogens disposition
      influencing tumour growth in hormone sensitive tissues. The UGT1A1*28
      distribution among an ovarian cancer patient (OCP) population of 217 mono
      institutional individuals was investigated to clarify its possible involvement in
      the pathogenesis and chemotherapy of ovarian cancer. Data were compared with
      those of 205 female healthy blood donors. In 160 patients also the tumour tissue
      was genotyped to describe the occurrence of loss of heterozygosity (LOH). A PCR
      based assay followed by automated fragment analysis was used. Odds ratios (OR),
      and 95% confidence intervals (95% CI), were computed by a multiple logistic
      regression model using as dependent variable in a case-control or in a case-case
      approach the histological classification. No significant prevalence of the
      polymorphism was observed in the cases versus controls. In a case-case approach,
      a higher frequency of the polymorphism was observed in patients with mucinous
      tumours (6/11, 54.6%) compared to non-mucinous (30/206, 14.6%) (p=0.009, OR=7.20;
      95% CI 2.06-25.19). LOH was observed in 12 cases out of 160 (7.5%) and was
      associated with non-mucinous tumours, 10 (83.3%) cases determined a retention of
      the wild-type allele. In conclusion, the prevalence of UGT1A1*28 found in
      mucinous OCP could suggest a role in the development of specific histologic sub
      groups and could become a marker to be considered when planning ovarian cancer
      chemotherapy.

PMID- 15254717
TI  - Mitochondrial DNA mutations in chemical carcinogen-induced rat bladder and human
      bladder cancer.
AB  - Mitochondrial (mt) DNA mutations have been described recently in different
      tumors, whereas similar studies focusing on bladder cancer are scarce. In an
      effort to understand the significance of mtDNA mutations in bladder cancer, we
      investigated the mtDNA alterations in both clinical human bladder cancer and in a
      carcinogen-induced rat bladder cancer model. Human bladder cancer tissues were
      obtained by radical cystectomy and transurethral resection of bladder tumors. Rat
      bladder tumors were induced in SD rats by treatment with N-butyl-N-(4
      hydroxybutyl) nitrosamine in drinking water for 24-28 weeks. Genomic DNA was
      extracted from tumor specimens and microdissected normal bladder mucosae.
      Mitochondrial genes and D-loop region were amplified by PCR. The amplified PCR
      fragments were either cloned into plasmid vector or used for direct DNA
      sequencing. The results of DNA sequence revealed numerous point mutations in the
      non-coding D-loop region and different mtDNA genes in both human and rat bladder
      cancers. In addition, we also detected deletions of variable lengths in
      mononucleotide repeats in the D-loop region, ND2, ATPase 8 and COIII genes in
      human bladder cancer samples. Our results show that mtDNA exhibits a high rate of
      mutations in both human and rat bladder cancers. We also demonstrate that the
      repetitive sequences of mononucleotides within the mt genome are unstable and
      subjected to deletions. The high incidence of mtDNA mutations in bladder cancer
      suggests that mtDNA and mitochondria could play an important role in the process
      of carcinogenesis and also mtDNA could be valuable as a marker for early bladder
      cancer diagnosis.

PMID- 15254718
TI  - Pegulated liposomal doxorubicin and cisplatin given concurrently with
      conventional radiotherapy: a phase I dose-escalation trial for patients with
      squamous cell carcinoma of head and neck and lung.
AB  - This is a phase I study of concurrent chemoradiation with pegulated liposomal
      doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung
      cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and
      9 with SCCHN were recruited in two phase I dose-escalation trials. The starting
      dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments
      for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for
      6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and
      70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of
      PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose
      limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three
      chemoradiation delays of 7 days were confirmed. The median time of follow-up was
      17.9 months (range 3-36 months). Four patients died due to local-regional failure
      combined with distant metastases (3 patients) and pericardial effusion (1
      patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%),
      and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II
      PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The
      incorporation of PLDH in concomitant chemoradiation regimens for future treatment
      of squamous cell carcinoma of the lung and head and neck is warranted.

PMID- 15254719
TI  - The localisation and reduction of nuclear staining of PPARgamma and PGC-1 in
      human breast cancer.
AB  - Peroxisome proliferator activated receptor-gamma (PPARgamma) belongs to a family
      of nuclear receptors and acts as a receptor for peroxisome proliferators,
      steroids, retinoic acids and polyunsaturated fatty acids. The current study
      examined both the transcript levels of PPARgamma and its coactivator PGC-1, and
      the localisation of these molecules in breast cancer tissues. Both PPARgamma and
      PGC-1 were located exclusively within the nucleus of epithelium and breast cancer
      tissues. Nuclear staining of both molecules was weaker in cancer cells compared
      with normal mammary epithelium. Computerised image analysis was used to quantify
      the immunohistochemical staining intensity, and this demonstrated that normal
      back-ground breast tissue exhibited higher levels of both PPARgamma (mean +/- sd,
      4.57+/-1.03) and PGC-1 (2.84+/-0.64), respectively. In contrast, tumour tissue
      exhibited significantly lower levels of PPARgamma (1.45+/-0.74, p<0.001 versus
      normal background tissue) and for PGC-1 (1.23+/-0.60, p<0.001 versus normal
      background tissue). This study also showed a variation in the levels of PGC-1 and
      PPARgamma between ductal and lobular tumours. These findings were corroborated by
      mRNA analysis which also demonstrated lower levels of both PGC-1 and PPARgamma in
      breast tumour tissue. It is concluded that both PPARgamma and its coactivator PGC
      1 play important roles in the development and progression of breast cancer, and
      may have a significant bearing on patient prognosis.

PMID- 15254720
TI  - Basal and luminal breast cancers: basic or luminous? (review).
AB  - Three major, fast developing lines of research are elucidating the biology of the
      mammary gland and its malignant transformation: phenotypical analyses of
      epithelial cells and mammary proliferative lesions, the identification,
      purification and characterization of mammary stem cells and breast cancer
      initiating cells, and gene expression profiling studies using high-throughput
      microarray technologies. These three approaches are providing a flux of new,
      increasingly coherent information and are improving cellular and molecular models
      of breast epithelium and its malignancies. A new conceptual framework is
      emerging, altering viewpoints on the differentiation and transformation of the
      mammary epithelial cells. The combined effects of these progresses on our
      understanding of breast cancer biology should have major consequences on the way
      this disease is managed.

PMID- 15254721
TI  - Expression of the heat shock cognate protein HSP73 correlates with tumour
      thickness of primary melanomas and is enhanced in melanoma metastases.
AB  - Seeking to identify melanoma-associated genes by comparing gene expression in
      uncultured primary melanoma specimens with those in nevi, from which melanomas
      often are known to arise, we applied subtractive suppression hybridization.
      Generating a subtracted library of candidate genes up-regulated in primary
      melanomas, this library contained cDNA fragments of the genes encoding heat shock
      cognate protein (HSP73) and major histocompatibility complex (HLA-DR) which were
      overexpressed in further 19 independent melanoma resection specimens on cDNA
      Southern blots when compared to 19 acquired melanocytic nevi. Upon
      immunohistochemistry, HSP73 protein expression was detected in the cytoplasm of
      melanoma cells in primary tumours and metastases. In primary melanomas, the
      proportion of HSP73 protein expressing cells correlated with tumour thickness
      according to Breslow which was statistically significant. HSP73 immunostaining
      was stronger in melanoma metastases when compared with acquired melanocytic nevi
      which was statistically significant. In addition to melanoma, gastric and uterus
      cancer tissues exhibited higher HSP73 mRNA expression on a matched tumour/normal
      cDNA array than their normal counterparts which was statistically significant.
      Participating in the regulation of folding, assembly and degradation of proteins
      and protecting cellular proteins from the damage caused by cellular stress like
      hypoxia or changes in cellular pH, elevated HSP73 expression possibly confers
      proliferative advantage on melanoma cells.

PMID- 15254722
TI  - Prognostic stratification of Dukes B colon cancer by a neoglycoprotein.
AB  - Disease progression of tumors is accompanied by structural changes of the glycan
      chains of cellular glycoconjugates. Within the concept of the sugar code the
      presence of complementary receptors such as lectins translates changes in ligand
      presentation into biological effects, for example in growth regulation and
      adhesion. By introducing neoglycoproteins to histopathological colon cancer
      analysis the questions are addressed as to whether specific binding sites for
      main N- and O-glycan components are present and whether they harbor potential for
      prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose
      derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical
      analysis. The tumor panel included routinely fixed tissue sections from 67 cancer
      cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6
      hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative
      image analysis determined the labeling index and the mean optical density in each
      case, separating tumor and peritumoral connective tissue. Specific carbohydrate
      dependent binding with inter-individual heterogeneity was observed. The distinct
      staining profiles were not associated with disease stage or metastasis formation.
      Strong expression of lactose-binding sites in the peritumoral connective tissue
      especially in terms of the labeling index was significantly correlated with
      reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in
      the Dukes C group. In conclusion, the application of the synthetic markers aimed
      at lectin detection defines lactose binding as new prognostic marker. It has
      potential relevance for improving the benefit from adjuvant therapy in Dukes B
      colorectal cancer patients. Technically, chemical ligand immobilization to an
      inert carrier can find useful application beyond glycosciences in the quest to
      extend the panel of tumor markers.

PMID- 15254723
TI  - Chromosomal alterations in breast cancer revealed by multicolour fluorescence in
      situ hybridization.
AB  - The aim of this study was to characterise cytogenetically, breast cancer cell
      lines and primary tumours to identify chromosomal regions of interest in breast
      cancer. Multicolour fluorescence in situ hybridization (MFISH) and comparative
      genomic hybridization (CGH) were used to karyotype five established breast cancer
      cell lines and two short-term primary tumour cultures. Chromosome 8 was
      identified as a frequent target for aberrations in all cell lines and one primary
      culture by MFISH and CGH. CGH identified frequent gains of 1q (all samples) and
      14q (all cell lines) and deletion of 22q (all samples). MFISH revealed a t(9;17)
      translocation in both primary tumours and the T47D cell line. MFISH analysis of
      the cell lines revealed a significant number of translocations previously
      unidentified in other studies using similar techniques, highlighting the
      necessity of utilising data from both primary cultures and established cell lines
      when investigating complex cytogenetic aberrations using MFISH and CGH.

PMID- 15254725
TI  - High cell surface expression of Newcastle disease virus proteins via replicon
      vectors demonstrates syncytia forming activity of F and fusion promotion activity
      of HN molecules.
AB  - For functional studies, the hemagglutinin-neuraminidase (HN) and the fusion
      protein (F) of Newcastle disease virus (NDV) were expressed in BHK cells using
      two vectors which are based on the Semliki Forest virus (SFV) replicon. The first
      system of high protein expression works by transfection of RNA which before has
      been in vitro transcribed from a vector containing the gene for the SFV self
      amplifying replicase (REP) and a foreign gene using the SP6 promoter. A high
      level of protein (HN or F) expression was detected 18-20 h after transfection. To
      study the host range of this expression system, a panel of different cell lines
      were compared for transfections with SFV RNA. A wide range of expression
      efficiency was observed, the highest being BHK cells. The second system is based
      on a DNA plasmid in which the SFV-REP and a foreign gene are expressed in cells
      under the transcriptional and translational control of the cytomegalovirus
      immediate-early enhancer T7 promoter. DNA-electroporated BHK cells expressed also
      high levels of the recombinant proteins but at a delayed time point (40-48 h) as
      compared with the corresponding RNA. Co-expression of the two NDV proteins, HN
      and F, via this DNA vector in the same cells led to syncytium formation in the
      cell monolayer, showing that both proteins expressed in this way, were
      functionally active. F alone, expressed via this vector, displayed residual
      fusion activity suggesting its proteolytic cleavage and its functional
      independence from HN.

PMID- 15254724
TI  - Overexpression of CD105 in rat myoblasts: role of CD105 in cell attachment,
      spreading and survival.
AB  - CD105 is a receptor for transforming growth factor-beta but it is also considered
      to be involved in cellular functions such as cell adhesion and migration. Using
      CD105 transfected rat myoblasts, we have investigated the role of CD105 in cell
      adhesion, spreading, growth and migration. CD105 transfected myoblasts expressed
      abundant CD105, which was preferentially located within focal adhesion sites.
      These cells took on a bipolar morphology whereas mock cells remained polygonal or
      rounded, and when wounded, CD105 expressing cells realigned their long axis prior
      to migrating and migrated as a cohort of cells. CD105 expression promoted
      cellular attachment, spreading, survival and growth in serum-free conditions and
      each of these parameters could be inhibited by a RGD-containing peptide but not a
      RAD-containing peptide. Mock-transfected cells could not attach, spread or grow
      under these conditions. Attachment, spreading and growth in CD105 expressing
      cells could be promoted by the addition of a monoclonal antibody against CD105.
      Expression of CD105 resulted in the phosphorylation of JNK1 but had no effect on
      beta1 integrin expression. From this preliminary study, we conclude that in
      addition to acting as a transforming growth factor-beta receptor, CD105 has an
      important role in cell adhesion, migration and survival.

PMID- 15254726
TI  - Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic
      acid treated primary and metastatic melanoma cells.
AB  - We have previously shown that all-trans-retinoic acid (atRA) induces apoptosis in
      melanoma cells and primary melanoma cells are more sensitive to the exposure of
      atRA than the matched metastases. However, mechanisms behind the atRA-induced
      apoptosis have not been studied. In this study, we used a similar cell culture
      model system of matched primary and metastatic melanoma cells from the same
      patient to investigate whether p53 and bcl-2 family proteins were involved in
      atRA-induced apoptosis. The primary and metastatic melanoma cells were exposed to
      0.1 and 10 micro M atRA in serum-free RPMI 1640 cell culture medium in the dark
      for up to 96 h. The protein expression of p53, p21, bax and bcl-2 were examined
      by Western blotting and immunocytochemistry. Expression of p53, p21 and bax was
      increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at
      different concentrations for various periods of time. The changes of p53, p21,
      bax, and bcl-2 protein levels were dose- and time-dependent. The primary melanoma
      cells were more sensitive to the atRA treatments than cells from matched
      metastatic melanoma. These data indicate that p53, p21, bax and bcl-2 proteins
      were involved in atRA-induced apoptosis in melanoma cells. Modification of these
      protein levels in the tumour cells might be beneficial for early treatment of
      melanoma.

PMID- 15254727
TI  - Implication of bax in apoptosis depends on microtubule network mobility.
AB  - Paclitaxel and vincristine sulfate, two anti-microtubule agents are known to
      induce apoptosis. In this study, we tried to apprehend the relationship between
      the regulation of apoptotic proteins such as the Bcl-2-family proteins and the
      cytoskeleton structure during apoptosis induction by these two drugs. Paclitaxel
      and vincristine sulfate were used for a 24-h incubation and resulted in EC50 of 1
      micro M and 1 micro g/ml, respectively. Under these conditions, paclitaxel
      treatment induced microtubule network polymerization, condensation of chromatin,
      characteristic features of early and late apoptosis as confirmed by orange
      acridine and ethydium bromide double staining. However, the shape of cells was
      not modified, while mitochondria changed their conformation from filamentous to
      aggregated corpuscles located around the nucleus. In addition, pro-apoptotic Bax
      protein remained in the cytoplasm, the beta-tubulin polymerization induced
      phosphorylation and inactivation of anti-apoptotic Bcl-2 and/or BclX/L proteins
      leading to intense mitochondria swelling and membrane disruption that are
      responsible for observed cytochrome c release and apoptotic proceeding. On the
      contrary, after vincristine sulfate treatment we observed morphological
      modifications such as cell shrinkage and nucleus condensation as the result of
      beta-tubulin depolarization and disruption of microtubules. Bax protein was
      intensively translocated into mitochondria membrane, decreasing the proportion of
      Bax/Bcl-2 or Bax/Bcl-xL heterodimers allowing the release of cytochrome c from
      the mitochondria and apoptotic process. In conclusion, our study demonstrated
      that the two anti-microtubule agents (paclitaxel and vincristine sulfate) induced
      apoptosis by two different pathways. However, mitochondrial dysfunction followed
      by cytochrome c release are the crucial events whatever the apoptotic signal,
      polymerization or disruption of beta-tubulin.

PMID- 15254728
TI  - Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis.
AB  - Fetuin, a major serum glycoprotein secreted by the liver, has been shown to play
      a role in bone development, calcium homeostasis and insulin sensitivity. In an
      earlier study, we demonstrated that bovine fetuin can bind to the plasma membrane
      of squamous and spindle-cell carcinoma cells. To test our hypothesis that fetuin
      plays a causal role in skin tumorigenesis, fetuin-A null and wild-type mice were
      challenged using a two-stage chemically-induced carcinogenesis protocol with DMBA
      (7,12-dimethylbenzo(a)anthracene) as the initiator, followed by twice weekly
      treatments with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate).
      Tumors that developed on fetuin-A null animals grew at a similar rate as those
      arising on their wild-type counterparts. Absence of fetuin-A did not alter tumor
      onset or conversion to squamous cell carcinoma, but reduced the number of tumors
      per mouse by 30%. This correlated with a decrease in tumor burden in fetuin-A
      null animals compared to wild-type weeks 18-22 from tumor onset. In addition,
      tumors arising on fetuin-A null mice had a diminished proliferative index with no
      change in cell survival or neovascularization in comparison with wild-type
      tumors. Our results suggest that fetuin-A contributes to early stages of skin
      tumorigenesis.

PMID- 15254729
TI  - Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid.
AB  - Arsenic is an environmental chemical of considerable concern due to its
      association with an increased risk of human cancer. Dimethylarsinic acid (DMAA)
      is one of the major methylated metabolites of ingested arsenicals in most
      mammals. To better clarify the role of metallothionein (MT) in modifying DMAA
      genotoxicity, MT-I/II null mice, and the corresponding wild-type mice, were
      exposed to DMAA (0, 188, 375 or 750 mg/kg body weight) via a single oral dose.
      Twenty-four hours after the DMAA injection, there was increased formation of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) in serum and urine and a higher number of DNA
      strand breaks in peripheral blood cells. These increased levels were concomitant
      with increasing dose concentrations of DMAA in both strains of mice and they were
      significantly higher in MT-I/II null mice than in wild-type mice. Furthermore,
      the induction of apoptotic cells in the urinary bladder epithelium of MT-I/II
      null mice was significantly higher than in dose-matched wild-type mice exposed to
      DMAA. On the other hand, in both liver and in the alveolar and bronchial areas of
      the lung, the extent of DMAA-induced apoptosis was not different between wild
      type and MT-I/II null mice and was increased in both strains. In addition, the
      concentration of hepatic MT in wild-type mice increased in a DMAA dose-dependent
      manner but was undetectable in MT-I/II null mice and could not subsequently be
      induced by DMAA. In conclusion, DMAA exposure causes oxidative stress, DNA damage
      and specific induction of apoptosis in target organs of arsenic carcinogenesis,
      which may be attributable to the mechanism(s) of arsenic-induced carcinogenesis
      in rodents. MT exhibited some protective roles during DNA damage presumably by
      acting as an antioxidant.

PMID- 15254730
TI  - Anti-angiogenic gene therapy for cancer (review).
AB  - Angiogenesis is a prerequisite for the growth and metastasis of solid tumors.
      Studies have confirmed that in the absence of angiogenesis, tumors rarely have
      the ability to develop beyond a few millimeters in diameter. Tumor-associated
      endothelium is activated by the production of soluble factors by tumor and
      stromal cells. Tumor-associated endothelial cells are physiologically homogeneous
      and divide more frequently. Thus, targeting the proliferation of tumor
      neovasculature will form an effective anti-cancer therapy. With the
      identification of drug and biological molecules that inhibit the growth of tumor
      endothelium, several attempts have been made in preclinical and clinical research
      to evaluate the potential of anti-angiogenic therapy. Although several drugs and
      purified proteins have shown promise, their wide-spread application is limited by
      half-life, side effects and cost involved. Gene therapy approaches, on the other
      hand, have the potential to overcome these limitations. Further, genetic transfer
      of anti-angiogenic genes can be combined with other treatments including
      radiation therapy or chemotherapy for synergistic effects. In this review, we
      provide a comprehensive account of factors and mechanisms underlying tumor
      angiogenesis, the potential and limitations of available gene therapy vectors for
      anti-angiogenesis and current status of preclinical and clinical gene therapy
      studies targeting tumor angiogenesis.

PMID- 15254731
TI  - Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in
      Epstein-Barr virus-immortalized B lymphocytes.
AB  - IL-6-mediated B-cell growth promotion is involved in the pathogenesis of EBV+
      lymphoproliferative disorders of immunosuppressed patients. Since retinoic acid
      (RA) inhibits the proliferation of EBV-immortalized lymphoblastoid B-cell lines
      (LCLs), we have investigated the effects of RA on IL-6 signaling in these cells.
      RA down-regulated IL-6-receptor components with IL-6 agonist activity (membrane
      and soluble gp80) and increased the levels of soluble gp130, an IL-6 antagonist.
      These changes, however, were not related to the enhanced production of endogenous
      IL-6 induced by RA in LCLs. RA-induced modulation of IL-6 receptor components did
      not abolish IL-6-mediated phosphorylation of gp130, whereas JAK1 and STAT3
      phosphorylation and activation induced by IL-6 were markedly inhibited. Overall,
      the effects of RA resulted in the induction of a complete resistance of LCLs to
      IL-6-mediated growth promotion. Conversely, RA did not inhibit the constitutive
      activation of JAK1, TYK2, STAT3 and ERK1/2, ruling out that the JAK/STAT and MAPK
      pathways may mediate the antiproliferative activity of RA. The finding that RA
      severely impairs IL-6-dependent signalings in LCLs and inhibits their growth
      despite the presence of constitutively active JAK/STAT and MAPK cascades provide
      additional support for a role of RA in the prevention and treatment of EBV
      related lymphoproliferative disorders of immunosuppressed patients.

PMID- 15254732
TI  - In vitro and in vivo antitumor activity of novel amphiphilic dimers consisting of
      5-fluorodeoxyuridine and arabinofuranosylcytosine.
AB  - Various heterodinucleoside phosphates of 5-fluorodeoxyuridine (5-FdUrd) and
      arabinofuranosylcytosine (Ara-C) have recently been synthesized as potent
      chemotherapeutic agents. 5-Fluorodeoxyuridine is being used in patients with
      colorectal carcinoma, whereas Ara-C is one of the most effective agents in the
      treatment of hematological malignancies. We now investigated the action of three
      novel amphiphilic dimers with different structures in various 5-fluorouracil (5
      FU) sensitive and resistant human colon tumor cell lines (CCL228, CCL227, 5-FU
      resistant CCL227 and HT-29) as well as in L1210 murine leukemia cells. Activity
      of the heterodimers was determined by clonogenic and growth inhibition assays
      including the induction of programmed cell death. In addition, the in vivo
      effects were tested in L1210 leukemia bearing mice. We show that these compounds
      inhibited the number of colonies of 5-FU sensitive and resistant human colon
      tumor cell lines with IC50 values ranging from 0.65 to 1 nM. The investigated
      dimers induced dose-dependent apoptosis in HT-29 colon tumor cells as well as in
      L1210 leukemia cells. No significant difference in the cytotoxicity of these
      agents could be observed between 5-FU sensitive and resistant cells, indicating
      that these compounds might be used in the treatment of 5-FU resistant tumors. In
      L1210 leukemia bearing mice the survival of tumor-bearing animals was
      significantly increased in comparison with untreated control animals. We
      therefore conclude that these new heterodinucleoside phosphates of 5-FdUrd and
      Ara-C might be an additional option for the treatment of sensitive and 5-FU
      resistant colon cancer and hematological malignancies.

PMID- 15254733
TI  - Anti-angiogenic and anti-tumor apoptotic activities of SJ-8002, a new piperazine
      derivative.
AB  - A new piperazine derivative, SJ-8002, is a synthetic anti-cancer agent which
      exhibits microtubule-inhibiting activities. In this study, we investigated the
      possibility that this compound inhibits angiogenesis and induces tumor-cell
      apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular
      carcinoma cells (HepG2) as a model system, respectively. In vivo, SJ-8002
      decreased the neovascularization of chick embryos and the basic fibroblast growth
      factor (bFGF)-induced angiogenesis in the chorioallantoic membrane (CAM) and the
      mouse Matrigel implants, respectively. In vitro, SJ-8002 treatment resulted in
      the inhibition of proliferation, migration, invasion and tube formation, and of
      matrix metalloproteinase-2 (MMP-2) expression in BAECs. In addition, the SJ-8002
      treatment in HepG2 cells reduced cell viability, and caused the production of
      fragmented DNA and the morphological changes corresponding to apoptosis including
      condensed and fragmented DNA in a concentration-dependent manner. SJ-8002 also
      elicited the release of cytochrome c and the activation of caspase-3. Therefore,
      it is possible that SJ-8002 functions as both angiogenesis inhibitor and
      apoptosis inducer. Taken together, these results suggest that SJ-8002 may be a
      candidate for strong anti-cancer agent with the ability to inhibit the
      angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

PMID- 15254734
TI  - A novel cysteine protease HeLa DUB-1 responsible for cleaving the ubiquitin in
      human ovarian cancer cells.
AB  - The regulation of ubiquitin-mediated protein degradation is becoming important
      for a number of cellular processes. Human HeLa DUB-1 cDNA, encoding a novel
      deubiquitinating enzyme, was isolated from ovarian cancer cells. It has 1,647 bp
      nucleotides and encodes a 548 amino acid polypeptide with the molecular weight of
      approximately 61 kDa. It contains the highly conserved Cys, Asp (I), His, and
      Asn/Asp (II) domains characteristic of the ubiquitin-specific processing
      proteases. Biochemical assay revealed that HeLa DUB-1 has deubiquitinating enzyme
      activity in vivo and in vitro. Northern blot analysis for HeLa DUB-1 showed the
      strong expression in human skeletal muscle and pancreas and to some extent in
      heart, placenta, lung, liver, and kidney. Interestingly, the expression was
      hardly seen in the brain. Localization study indicates that HeLa DUB-1 proteins
      are present in both the cytoplasm and nucleus.

PMID- 15254735
TI  - Truncation of the mismatch repair protein PMS2 during the neoplastic
      transformation of human breast epithelial cells in vitro.
AB  - Alterations in known mismatch repair (MMR) genes have been found in many cancers,
      such as in hereditary non-polyposis colorectal cancer syndrome (HNPCC), in
      addition to specific oncogenes and tumor suppressor gene abnormalities. We have
      reported mutations in the MMR genes hMSH2, hPMS2 and hMSH6 in human breast
      epithelial cell lines (HBEC). In hPMS2 we found a non-sense mutation in codon
      number 471 by a change of glutamine (CAG) by stop codon (TAG). We also observed
      that the number of alterations in the MMR genes were increased during the process
      of cell transformation and tumorigenesis. In the present study in order to
      determine the role of those mutations in the hPMS2 protein activity, we used
      western blotting, protein truncation test and MMR activity assay employing HBEC
      cells. In the transformed and tumor cell lines we found a premature hPMS2 protein
      truncated by western blot and also we confirmed this truncation using the protein
      truncation test. In the MCF-10F cells only the wild-type hPMS2 protein was
      detected. The functionality of the hPMS2-truncated protein was confirmed by DNA
      heteroduplex assay using specific mispaired bases in mutated M13mp2 phages. DNA
      repair activity was proficient in MCF-10F cells, partially deficient in the
      transformed cells, and totally deficient in the tumor cell lines. In order to
      test whether the MMR deficiency was due to an hPMS2 defect, we used the wild-type
      heterodimer hPMS2-hMLH1 in the in vitro reaction of DNA heteroduplex assay; we
      have found that addition of the hPMS2 wild-type increased the MMR repair
      efficiency by more than 40% in tumor cell lines. Our results indicate that a
      protein-truncating mutation in the hPMS2 gene had occurred during the process of
      cell transformation and tumorigenesis and that truncation is related to a lack of
      function of this gene.

PMID- 15254736
TI  - An investigation of the tylosis with oesophageal cancer (TOC) locus in Iranian
      patients with oesophageal squamous cell carcinoma.
AB  - Oesophageal cancer is one of the ten leading causes of cancer mortality
      worldwide. Earlier loss of heterozygosity (or allelic imbalance) studies have
      implicated regions on chromosomes 3p, 5q, 9p, 13q, 17p, 17q, and 18q in the
      development of sporadic oesophageal cancer and recent data have linked the
      familial tylosis with oesophageal cancer (TOC) gene-containing region on
      chromosome 17q25 with this cancer. We have studied allelic imbalance (AI) at
      microsatellite markers both closely linked to and distant from the TOC gene locus
      in 60 sporadic squamous cell oesophageal cancers from Iran and have investigated
      the most likely candidate gene by mutation analysis in these tumours. Forty-four
      out of these 60 samples (73%) show allelic imbalance at one or more loci within
      or adjacent to the TOC minimal region, while the highest incidence of AI was
      observed at the D17S2244 and D17S2246 loci (almost 70% AI in informative cases),
      correlating with the TOC minimal region. Analysis of the coding regions of a
      candidate gene in these tumours failed to show an equivalently high incidence of
      mutation, although two mutations and one polymorphism were observed. These data
      support and extend previous observations that the TOC region of chromosome 17q25
      may be involved in the aetiology of the sporadic form of oesophageal cancer from
      a number of different geographical populations and suggest that the causative
      gene may be epigenetically silenced rather than mutated.

PMID- 15254737
TI  - A close association between alteration in growth kinetics by neoadjuvant
      chemotherapy and survival outcome in primary breast cancer.
AB  - Few surrogate markers are available for predicting the survival benefit from
      chemotherapy in primary breast cancer. We examined tumor growth kinetics by
      assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by
      M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody
      in 72 primary breast cancer patients who underwent pre-operative anthracycline
      based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the
      exposure of 2 to 4 cycles of chemotherapy correlated significantly with
      pathological tumor response. Univariate survival analysis, conducted in the
      subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU)
      therapy alone, showed that the patients with the high levels of M30 index (>35
      counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000
      tumor cells) after chemotherapy had a remarkably favorable prognosis as compared
      with patients in other categories. In addition, the alteration in growth kinetics
      by the treatment showed a significant prognostic value. Multivariate analysis
      also confirmed that the post-treatment growth kinetics was an independent
      prognostic indicator. These findings suggest that the alteration in growth
      kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting
      the survival benefit from chemotherapy in primary breast cancer.

PMID- 15254738
TI  - The immunosuppressive effect of vincristine on allostimulatory potential of human
      dendritic cells interferes with their function and survival.
AB  - Mature dendritic cells (mDC) are professional and potent antigen presenting cells
      required for initiation of primary immune responses. In the present study, we
      have investigated the effect of vincristine on the T cell allostimulatory
      potential of human monocyte-derived mDC in allogeneic mixed lymphocyte reaction.
      Using T lymphocytes as responding cells and mDC as stimulating cells, our data
      indicate that incubation of DC with vincristine decreased the accessory potency
      dose dependently and resulted in a subsequent inhibition of T cell proliferative
      responses. Treatment of mDC with vincristine also led to the alteration of their
      capacity to produce IL-12 but enhanced their production of IL-10. Using flow
      cytometry, we demonstrated that vincristine had no effect on mDC phenotype (CD83,
      CD40, CD86, CD58, CD54) but promoted apoptotic cell death of these cells as
      revealed by PI and annexin-V. These findings suggest that DC may be potential
      targets of cytotoxic drugs and point out the possible impairment of the
      immunocompetence of these cells following chemotherapy.

PMID- 15254739
TI  - The subunits of glutamate cysteine ligase enhance cisplatin resistance in human
      non-small cell lung cancer xenografts in vivo.
AB  - Glutamate cysteine ligase (GCL) is a key enzyme in glutathione (GSH) synthesis,
      and is thought to play a significant role in the intracellular detoxification of
      anticancer drugs, especially of cisplatin (CDDP). GCL is composed of a modifier
      or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). It
      was unclear whether the subunits are essential to CDDP-resistance. We examined
      the gene expression of GCLM and GCLC in 39 xenografts of human non-small cell
      lung cancer [NSCLC; 10 adenocarcinoma (Ad), 17 squamous cell carcinoma (Sq) and
      12 large cell carcinoma (La)] by real-time polymerase chain reaction (PCR) with
      human-specific primers. Drug sensitivity to CDDP was evaluated in the 9
      xenografts (4 Ad, 2 Sq and 3 La) using an in vivo drug sensitivity test. There
      was a significant association between the expression of GCLM and GCLC mRNA in
      each xenograft (Fisher's test, p<0.045). Squamous cell carcinoma xenografts
      significantly showed higher expression of GCLM gene than adenocarcinoma
      xenografts (p=0.023, t-test), while there was no significant difference in GCLC
      gene expression levels between each histopathological xenograft. Three of nine
      xenografts were sensitive to CDDP (Mann-Whitney U test, p<0.01, one-sided), while
      the other 6 xenografts were resistant. There was a significant relationship
      between drug sensitivity to CDDP and the co-overexpression of GCL subunits (chi2
      test for independence, Yates' correction, p=0.014). These results suggested that
      the co-overexpression of GCL subunits correlated with CDDP-resistance in human
      NSCLC xenograft in vivo.

PMID- 15254740
TI  - Correlation of the response of recurrent malignant gliomas treated with
      interferon alpha with tumor interferon alpha gene content.
AB  - Malignant gliomas are treated by combining surgery and radiation with
      chemotherapy. Cure is rare and utilizing information arising from our improved
      understanding of brain tumor biology may be of value. Interferon alpha (IFNalpha)
      treatment as restorative immunotherapy has been utilized in malignant gliomas in
      the past. Interferon alpha/beta gene presence is variable in these tumors. The
      relationship between response to IFNalpha therapy and gene status has not been
      assessed prospectively. Patients with recurrent malignant gliomas were treated
      with 8-week courses of IFNalpha. Clinical and laboratory toxicity was assessed
      and response determined by MRI scans. Tumor interferon alpha/beta gene content
      was measured. Toxicities included fourteen grade 3/4 neuro-motor events, and
      eleven grade 3 neuro-cortical events. Rapid tolerance developed and with dose
      reductions few doses were missed. Three individuals with glioblastoma multiforme
      demonstrated a partial response. Median time to progression was 24.6 (+/-17.6)
      weeks for all glioblastomas. The correlation between longer time to progression
      and lower tumor IFNalpha gene content as measured here was significant. A
      minority of patients with recurrent malignant gliomas will respond to IFNalpha
      therapy at starting doses of 20 Mu/m(2) and above. These doses are associated
      with significant toxicity. A relationship between the tumor IFNalpha gene status
      and tumor response to therapy may be present. With current improved understanding
      of IFNalpha toxicities and ability to measure tumor IFNalpha function, this
      therapy warrants further evaluation for identifying patients whose tumors are
      likely to be responsive to IFNalpha therapy.

PMID- 15254741
TI  - Costs of follow-up after potentially curative treatment for extremity soft-tissue
      sarcoma.
AB  - Soft-tissue sarcoma is an uncommon cancer with the potential for high rates of
      recurrence after initial therapy. Multiple surveillance strategies have been
      developed to follow patients after primary treatment. The purpose of this study
      was to quantify the costs associated with various published post-treatment
      surveillance strategies. A literature review covering the years 1982-2003 was
      performed to find all modern published surveillance methods for extremity soft
      tissue sarcoma. Only articles describing an explicit 5-year follow-up strategy
      were included. Total costs of 5-year follow-up were calculated for each strategy
      using Medicare-allowed charges as a proxy. Thirty-four articles depicting 54
      strategies were identified. Total Medicare-allowed charges in year 2003 dollars
      ranged from 485 dollars for follow-up of low-grade sarcoma to 21,235 dollars for
      follow-up of high-grade sarcoma, a 42.8-fold cost differential. The average
      charge for these 54 strategies was 6,401 dollars. Physical examination and chest
      x-ray were the most commonly used screening modalities. Several guidelines have
      been proposed for extremity soft-tissue sarcoma patient follow-up, most
      prominently those of the National Comprehensive Cancer Network. The literature
      has yet to reflect the consensus these guidelines suggest. This study shows wide
      disparity in the costs of 54 specific methods of following soft-tissue sarcoma
      patients. Clinical trials are needed to identify an optimal surveillance
      strategy, one balancing gains in survival, quality of life, costs, and societal
      willingness to expend resources. Such trials have not been conducted due to the
      rarity of extremity soft-tissue sarcomas and the costs associated with conducting
      long-term trials. Alternatively, prospective evaluation of imaging modalities
      used in follow-up should be assessed as part of other trials. Computer simulation
      analysis also holds great promise as an assessment tool for surveillance
      strategies because patient participation is not required.

PMID- 15254742
TI  - Growth arrest and apoptosis in adult T cell leukemia cell lines following IL-2
      deprivation.
AB  - Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T
      cell leukemia virus type-I (HTLV-I). Since ATL cells often require IL-2 for their
      proliferation and survival, we examined the effect of IL-2 deprivation on the IL
      2-dependent ATL cells established from ATL patients. After IL-2 withdrawal, these
      cells were arrested in the G1 phase and then underwent apoptosis. p27Kip1 was
      observed to act as a cell cycle inhibitor. A decrease in the amount of Bcl-xL was
      more distinct than that of Bcl-2, while Bax increased slightly during IL-2
      withdrawal. The activation of caspase-3 and the loss of mitochondrial membrane
      potential were also observed. An overexpression of Bcl-xL protein in the KK1, one
      of the ATL cell lines, suppressed apoptosis by the 3rd day, however, apoptosis
      could not be prevented completely. Thereafter, a decrease in Bcl-xL and an
      activation of caspase-3 were observed even under the overexpression of Bcl-xL.
      The mitochondrial membrane potential and the intra-cellular levels of reactive
      oxygen species (ROS) also changed due to IL-2 deprivation. From these results,
      the IL-2 signals are considered to be essential for the survival of ATL cells,
      and the interruption of IL-2 signaling might thus be useful as a potentially new
      treatment for ATL.

PMID- 15254743
TI  - Mechanisms underlying the synergistic effect of SU5416 and cisplatin on
      cytotoxicity in human ovarian tumor cells.
AB  - SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF)
      receptors with anti-angiogenesis activity for human cancers. We have previously
      reported that SU5416 sensitizes ovarian cancer cells to cisplatin via suppression
      of nucleotide excision repair activity. This study sought to gain further
      insights into the mechanisms underlying the synergistic effect of SU5416 and
      cisplatin on cytotoxicity in human ovarian tumor cells. Here, we show that SU5416
      inhibited the expression of G1 cell cycle checkpoint regulators, p53, p21, p27
      and MDM2 in ovarian carcinoma cells. We also demonstrate that SU5416 triggered
      the apoptosis of these cells, in addition to augmenting the apoptosis induced by
      cisplatin, as determined by a Sub-G1 profile analysis using a flow cytometer.
      Furthermore, we show that SU5416-induced apoptosis is associated with a decrease
      in the expression of the apoptosis inhibitors, MDM2 and Bcl-2, and an increase in
      the level of NF-kappaB inhibitor, IkappaBalpha. NF-kappaB is an anti-apoptotic
      transcription factor, which induces the apoptosis inhibitors, Bcl-XL and IAPs
      (inhibitor of apoptosis proteins), and IkappaBalpha is an inhibitor of NF-kappaB,
      which binds to the NF-kappaB and retains it in the cytoplasm. Finally, the
      compound was found to block cisplatin-induced increases in AP-1 expression and
      JNK activity, as well as Raf-1 protein level in these cells. Together, these
      results suggest that the chemosensitizing effect of SU5416 on ovarian tumor cells
      may be mediated, at least in part, through inhibiting G1 checkpoint control and
      up-regulating the apoptotic response to cisplatin.

PMID- 15254744
TI  - Usefulness of immunomodulators for maturation of dendritic cells.
AB  - Biological response modifiers (BRMs) augment the cytotoxic activity of various
      effector cells by the induction of multiple cytokines and suppression of
      immunosuppressive factors. BRMs are used extensively in adjuvant therapy for
      gastric cancer in Japan. In dendritic cell (DC)-based vaccine therapy, the
      quality of DCs is important in inducing strong antitumor immunity. A good
      manufacturing practice (GMP) grade agent for DCs maturation is desirable for
      safety. Here we report the effects of two BRMs, OK432 and PSK, which are GMP
      grade agents for the functional maturation of DCs. OK432 and PSK were examined in
      vitro, and compared with lipopolysaccharide (LPS) and a cytokine cocktail (IL
      1beta, TNF-alpha, IL-6 and PGE2). In the immunophenotypical analysis, the
      expression of CD80 and CD83 of DCs stimulated with OK-432 increased significantly
      compared with PSK and medium, and this up-regulation was the same as levels of
      DCs stimulated with cytokine cocktail. DCs stimulated with OK-432 showed
      significantly higher production of IL-12 and Th1-type cytokines (IL-2 and IFN
      gamma) compared with DCs stimulated with LPS or cytokine cocktail. OK-432
      stimulated DCs could induce the significantly high level of cytotoxic T cell
      activity compared with PSK-stimulated or unstimulated DCs. These results suggest
      that OK432 is a GMP-grade reagent that promotes functional maturation of DCs and
      could be applied in DC-based vaccinations.

PMID- 15254746
TI  - Role for Raf in the entry of viruses associated with AIDS (review).
AB  - The biology of acquired immune deficiency (AIDS) is yet to be completely
      understood partly because it is complicated by the manifestation of various viral
      infections and associated pathogenesis. Virus entry into target cells is a key
      step in the virus replication cycle which is characterized by intricate and
      complex interactions between virus and host cells. Analyses of virus entry are
      always hampered to some extent due to the inability to mimic in vivo conditions.
      Emphasis has been placed on understanding what the virus does during the entry
      process; for example the signaling it mediates during entry, or identifying the
      cellular receptors with which the virus interact. Often, the role of the cellular
      environment that is critical for the complex process of virus uptake has taken a
      back stage. Interestingly, most of the viruses associated with AIDS cause tumors.
      In a recently concluded study, we identified a role for intracellular oncogenic
      (Raf) signaling in human herpesvirus-8 (HHV-8/KSHV) infection of target cells. In
      this review we present an update on entry of various viruses commonly associated
      with AIDS and yet another novel way of analyzing virus entry.

PMID- 15254745
TI  - Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal
      cancer.
AB  - Tumor tissues and adjacent normal tissues in 12 colorectal cancers were examined
      for quantitative differences in: i) activity of DNA-dependent protein kinase (DNA
      PK), which functions in DNA double-strand breads repair, and ii) protein and mRNA
      levels of Ku70, Ku80, DNA-PKcs and transcriptional factor Sp1. DNA-PK activity
      and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were significantly higher
      in the tumor tissues compared with the normal tissues. Significant correlations
      between DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1
      were observed. Because Ku80 and DNA-PKcs have consensus Sp1 recognition elements
      in their promoter region, the DNA sequence of Ku70 promoter region was analyzed.
      Analysis of Ku70 promoter region reveled that Ku70 gene has consensus Sp1
      recognition elements in its promoter region. mRNA levels of Ku70, Ku80 and DNA
      PKcs were correlated with one another, and significant correlations between Sp1
      protein level and mRNA levels of Ku70 and Ku80 were observed. These results
      suggest that DNA-PK activity and protein- and mRNA-levels of Ku70, Ku80 and DNA
      PKcs were elevated in tumor tissues in patients with colorectal cancer because of
      elevated Sp1 protein levels in tumor tissues.

PMID- 15254747
TI  - Diagnostic and classification value of metalloproteinases in squamous human
      laryngeal carcinoma.
AB  - Metalloproteinases (MMPs) are a class of enzymes largely involved in tumour
      progression and metastasis. At least twenty different enzymes are recognized that
      are also present under normal state of tissues. Their activity is regulated by
      their presence as proenzymes and by the concomitant presence of the respective
      tissue inhibitors (TIMPs). The present study describes the alterations of MMPs
      observed in human laryngeal carcinoma with respect to tumour classification and
      compares their activity in normal and cancerous tissues and biopsy specimens.
      Samples from five patients who underwent laryngectomy, from five biopsies and
      three from autopsies were used. The MMPs of normal and malignant human laryngeal
      cartilage and of biopsy specimens were identified immunochemically and by
      zymography using gelatin or casein as substrates. Healthy cartilage from
      autopsies was found to contain almost exclusively MMP-1, proMMP-2 and proMMP-9.
      Normal parts from laryngectomies contained, in addition, significant amounts of
      active MMP-2. The respective malignant parts contained both MMP-2 and -9 in
      increased amounts in their latent and active forms. Similar profile of MMPs was
      also identified in tissues surrounding affected cartilage. These alterations were
      found to be in good accordance with tumour stage and were also observed in biopsy
      samples. Thus, analysis of MMPs in biopsies can be used together with the
      clinicopathological parameters for the classification or early diagnosis of
      laryngeal tumours.

PMID- 15254748
TI  - MHC class I down-regulation: tumour escape from immune surveillance? (review).
AB  - Malignant conversion and subsequent in vivo selection can give rise to the cell
      populations that show stable expression of an immune escape phenotype, MHC class
      I deficient neoplasms. Deficiencies associated with the MHC class I down
      regulation are either irreversible, such as beta2 microglobulin and class I heavy
      chain gene disabling mutations, or reversible. The reversible MHC class I
      deficiencies involve all levels of the MHC class I-restricted antigen
      presentation machinery. They can be repaired, at least partially and in vitro, by
      cytokines (IFNgamma, TNFalpha) or by DNA demethylation/histone hyperacetylation
      procedures. The reduced levels of MHC class I antigens result in decreased
      sensitivity to MHC class I-restricted, cytotoxic T lymphocyte-mediated lysis, the
      major component of the tumour rejection reaction. MHC class I down-regulation
      helps tumour cells evade the classical T cell-dependent immune responses but
      simultaneously imposes another, the NK cell-mediated, surveillance stimulated by
      the 'missing self' signals. The innate and adaptive antitumour immunity may be
      under some conditions interconnected: primary activation of the MHC class I
      unrestricted surveillance mechanisms may lead to the production of IFNgamma by
      the activated NK/gammadelta T cells; the in situ produced IFNgamma may then up
      regulate the MHC class I molecule expression on the tumour cell surface and in
      this way it may stimulate the more efficient, MHC class I-restricted, adaptive
      immunity. If we accept that the MHC class I down-regulation can, under some
      conditions, indeed be a mechanism of the tumour escape from the immune defence,
      the problem arises how to cope efficiently with this escape. Either therapeutic
      procedures aiming at up-regulation of MHC class I expression, or enhancement of
      MHC class I-unrestricted (CD4+, NK, NKT, gammadelta T) tumour defence effector
      mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL
      12, IFNgamma, GM-CSF), or by the cytokine gene-based, genetically modified tumour
      vaccines should be considered.

PMID- 15254749
TI  - The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to
      inhibit proliferation and to induce apoptosis and differentiation of human
      glioblastoma cell lines.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in the
      control of cell proliferation, apoptosis and differentiation in various tumor
      cells. Among PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (PGJ2), the
      ultimate metabolite of PGD2, plays a role in the biology of brain tumors. It is
      still unclear to which extent the anti-proliferative and differentiation
      promoting activity of PGJ2 is mediated through PPARgamma. We compared the effects
      of PGJ2 with those of rosiglitazone - the synthetic agonist with the highest
      affinity for PPARgamma - in 4 human glioblastoma cell lines (A172, U87-MG, M059K,
      M059J). All cell lines expressed high levels of PPARgamma, consistent with the
      high levels of PPARgamma protein in 5 tumor samples. Both PGJ2 and rosiglitazone
      inhibited proliferation of all cell lines with a G2/M arrest and apoptosis, but
      only PGJ2 up-regulated p21Cip/WAF1. The growth inhibitory effect was partially
      reversed by the PPARgamma antagonist GW9662. We studied the time sequence of
      selected molecular events, that lead glioblastoma cells to apoptosis and/or
      differentiation, after treatment with both agonists. M059K cells committed to
      undergo apoptosis by PGJ2, initially up-regulated PPARgamma, and then down
      regulated PPARgamma as they began apoptosis. Apoptotic cells also increased their
      expression of retinoic acid receptor beta (RARbeta) and retinoid X receptor alpha
      (RXRalpha). PGJ2 increased expression of glial fibrillary acidic protein (GFAP)
      and decreased levels of vimentin, structural proteins modulated during astrocytic
      differentiation. Unexpectedly, PGJ2 up-regulated the expression of cyclooxygenase
      2 (COX-2). Rosiglitazone caused the same pattern of PPARgamma, RARbeta and
      RXRalpha expression as PGJ2, but no significant modulation of p21Cip/WAF1,
      cytoskeletal proteins or COX-2 occurred. Our data indicate that PGJ2, and
      rosiglitazone suppress cell proliferation and cause apoptosis in glioblastoma
      cell lines, most likely through a PPARgamma-dependent pathway. By contrast, the
      modulation of differentiation-associated proteins by PGJ2, but not rosiglitazone,
      suggests that PGJ2 promotes differentiation of glioblastoma cells independently
      of PPARgamma activation.

PMID- 15254750
TI  - Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate
      cancer cells by ectopic expression of 14-3-3zeta.
AB  - A promising family of anticancer agents, the camptothecins, is noted for their
      ability to induce apoptosis specifically in malignant cells. However, a major
      obstacle for successful cancer treatment by these and other chemotherapeutic
      agents is the intrinsic or acquired resistance to drug treatment. Resistance to
      9NC6, a camptothecin derivative, has been modeled in vitro using a human prostate
      cancer cell line. To elucidate the mechanism for acquired 9NC resistance, we have
      used a subtractive cloning approach to identify genes whose altered expression
      level is reflective of 9NC resistance or susceptibility. Differential gene
      expression was compared between wild-type human prostate cancer cell line, DU
      145, and a 9NC-resistant subline, RC1. Results were confirmed by Northern and
      Western blot analyses. In this report, we focus on one gene, 14-3-3zeta. An
      expression vector of a full-length myc-epitope-tagged 14-3-3zeta cDNA was
      constructed and used for transfection into DU-145 cells. We consistently observed
      that 14-3-3zeta message and protein levels were dramatically increased in 9NC
      resistant cells. The expression levels of other 14-3-3 family members were
      unaffected. Strikingly, ectopic overexpression of 14-3-3zeta in wild-type 9NC
      susceptible prostate cancer cells decreased 9NC-induced apoptosis. Our results
      suggest a novel direct or indirect role of 14-3-3zeta in mediating resistance of
      DU-145 cells to the topoisomerase I inhibitor, 9NC. We are currently exploring
      whether this represents a more general pathway for drug resistance as well.

PMID- 15254751
TI  - Vascular endothelial growth factor levels do not predict efficacy of systemic
      adjuvant treatment as assessed in 1127 breast cancer patients.
AB  - The vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and
      has proven to be of prognostic value in patients with primary breast cancer. In
      this study we investigated whether VEGF is of predictive value with regard to the
      efficacy of adjuvant systemic therapy in primary invasive breast cancer. In 1127
      tumors of patients with invasive breast cancer the cytosolic levels of VEGF were
      measured using a quantitative enzyme-linked immunosorbent assay. These patients
      were followed for a median follow-up time of 59 months (range 2-268 months) after
      primary surgery. Correlations with well-known prognostic factors, and univariate
      and multivariate survival analyses were performed. The VEGF levels showed a
      positive correlation with age, menopausal status and tumor size. In addition,
      VEGF levels were inversely correlated with estrogen and progesterone receptor
      levels. A high VEGF level predicted an early relapse in the univariate relapse
      free survival (RFS) analysis for all patients (P=0.010), but not in the
      multivariate analysis. Furthermore, there were no statistically significant
      interactions between the levels of VEGF and the use of adjuvant endocrine therapy
      or chemotherapy in the RFS analysis. We conclude that tumor levels of VEGF do not
      predict the efficacy of adjuvant endocrine therapy or chemotherapy in patients
      with primary breast cancer.

PMID- 15254752
TI  - Identification of a novel putative non-coding RNA involved in proliferation
      arrest of a non-small cell lung carcinoma cell line treated with an original
      chemical substance, methyl-4-methoxy-3-(3-methyl-2-butanoyl) benzoate.
AB  - Non-small cell lung cancers remain particularly refractory to current treatments.
      Thus, characterisation of new molecular targets whose expression during
      chemotherapy could stop tumour growth, is required. In order to identify these
      new targets, we applied RT-PCR differential display (RT-PCR-DD) to a non-small
      cell lung cancer line (NSCLC-N6) treated by an original chemical substance, VT1,
      capable of arresting the proliferation of NSCLC-N6 cells in G1 phase. This study
      enabled us to identify a novel RNA, which has a strong homology with a DNA clone
      (GenBank accession no.: AY166681). This RNA resides in 6p24-p25 within intron 2
      of the HEF1 gene, has no apparent open reading frame and may consists of a single
      large exon. Antisense oligonucleotides indicated that this RNA is involved in the
      proliferation arrest induced with VT1 treatment in NSCLC-N6 cells. The structure
      of this novel RNA resembles that of the previous identified extremely long non
      coding RNAs which seem to regulate gene expression. Thus, this novel B2
      transcript may belong to this new expanding non-coding RNA family.

PMID- 15254753
TI  - Identification and characterization of human HES2, HES3, and HES5 genes in
      silico.
AB  - MMTV induces the mouse mammary tumor through the dysregulation of Notch, Wnt, or
      Fgf signaling pathway. Activation of Notch signaling pathway leads to
      transcriptional activation of Hes family genes through the interaction between
      Notch intracellular domain and RBPSUH (CSL). Hes family proteins are mammalian
      homologs of Drosophila Hairy and Enhancer of split. Hes family of transcriptional
      repressors with basic Helix-loop-helix (bHLH) and Orange domains are implicated
      in the cell fate determination of stem cells (or precursor cells) by suppressing
      the expression of tissue-specific transcriptional activators. Human HES1, HES4,
      HES6, and HES7 genes have been reported by other groups. Here, we identified and
      characterized human HES2, HES3 and HES5 genes by using bioinformatics. FLJ33803
      (AK091122.1) was the representative human HES2 cDNA. HES2 gene, encoding a 173-aa
      protein, was located within human genome sequence AL031848.11. HES3 gene,
      encoding a 186-aa protein, was identified within human genome sequence
      AL031847.17. HES5 gene, encoding a 166-aa protein, was identified within human
      genome sequence AL139246.20. HES2 and HES3 genes were mapped to human chromosome
      1p36.31, while HES5 gene to 1p36.32. HES2 mRNA was expressed in placenta,
      pancreatic cancer, colon cancer with RER, cervical cancer, and in head and neck
      tumors. HES5 mRNA was expressed in fetal heart, and brain tumors. Human HES
      family proteins were found consisting of bHLH, Orange, Proline-rich domains, and
      WRPW motif. Phylogenetic analyses revealed that HES family proteins were
      distantly related except a paralog pair of HES1 and HES4. HES family genes are
      pharmacogenomic targets in the field of regenerative medicine and oncology.

PMID- 15254754
TI  - Identification and characterization of human ARHGAP23 gene in silico.
AB  - ARHGAP family genes, such as FNBP2, SRGAP1/ARHGAP13, SRGAP2/ARHGAP14, ARHGAP4 and
      AHRGAP20/KIAA1391, encode GTPase activating proteins for Rho family proteins
      (RhoGAPs). Here, we identified and characterized the ARHGAP23 gene by using
      bioinformatics. KIAA1501 (AB040934.1) was a 5'-truncated partial cDNA derived
      from the ARHGAP23 gene. Complete coding sequence of human ARHGAP23 cDNA was
      determined by assembling BM806021 EST, BQ718622 EST, KIAA1501 partial cDNA, and
      AC115090.8 genome sequence corresponding to exons 7 and 25. ARHGAP23 gene encoded
      1491-aa isoform 1 (without exon 23) and 1144-aa isoform 2 (with exon 23) due to
      alternative splicing. Isoform 2 was C-terminally truncated due to frame-shift
      within 23-bp exon 23. ARHGAP23 mRNA was expressed in placenta, prostate,
      hippocampus, brain medulla as well as in brain tumor, salivary gland tumor, head
      and neck tumor. Mouse 4933428G20 (NM_021493.1) was a 5'-truncated partial cDNA
      derived from Arhgap23 gene at mouse chromosome 11D. Human ARHGAP23, ARHGAP21 and
      Xenopus rGAP shared the common domain structure consisting of PDZ, Pleckstrin
      homology (PH), and RhoGAP domains. ARHGAP23-KIAA1684-MLLT6-RNF110-PIP5K2B-LASP1
      PLXDC1-CACNB1 locus at human chromosome 17q12 and CACNB2-PLXDC2-LASP2-MLLT10-BMI1
      PIP5K2A-KIAA1217-ARHGAP21 locus at human chromosome 10p12 were paralogous regions
      (paralogons) with internal inversion. MLLT6, MLLT10 and LASP1 genes are fusion
      partners of MLL gene in hematological malignancies, while RNF110, PIP5K2B, LASP1
      and BMI1 genes are amplified in human tumors. Evolutionary recombination hotspots
      and oncogenomic recombination hotspots were co-localized around the ARHGAP23
      CACNB1 locus and the ARHGAP21-CACNB2 locus.

PMID- 15254755
TI  - Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic
      chondrocytes.
AB  - Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in
      clinical practice in the treatment of osteoarthritis. There have been no reports
      regarding cross-talk between HA and COX-2 inhibitors in articular human
      chondrocytes. The purpose of this study was to investigate whether HA, COX-2
      inhibitors or a combination of COX-2 inhibitors and HA have different effects in
      human articular between lower and highly degenerated chondrocytes. Isolated lower
      and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as
      a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or
      no additive. After incubating for 48 h, mitochondrial membrane potential analysis
      and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK)
      were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin
      E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA
      resulted in dendritic, proliferating chondrocytes with strong red fluorescence
      enriched in the mitochondrial membrane, and indicated reduction of apoptosis in
      chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA
      inhibited the activation of p38 in highly degenerated chondrocytes. A combination
      of COX-2 inhibitors and HA decreased NO production in highly degenerated
      chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had
      no effect on PGE2 production. The present study demonstrated that COX-2
      inhibitors and HA interacted synergistically the MAPK pathway and inhibition of
      NO production in highly degenerated chondrocytes. Administration of COX-2
      inhibitors plus HA could be used as a new alternative way of treating
      osteoarthritis.

PMID- 15254756
TI  - Peptide nucleic acid-DNA decoy chimeras targeting NF-kappaB transcription
      factors: Induction of apoptosis in human primary osteoclasts.
AB  - Peptide nucleic acids (PNAs) are DNA mimics constituted by a pseudopeptide
      backbone composed of N-(2-aminoethyl)glycine units. PNAs hybridize with high
      affinity to complementary sequences of single-stranded RNA and DNA, forming
      Watson-Crick double helices and are resistant to both nucleases and proteases.
      While applications of PNAs as antisense and antigene molecules have been
      described, PNA/DNA and PNA/PNA hybrids are not useful for transcription factor
      decoy (TFD) pharmacotherapy. By contrast, PNA-DNA-PNA (PDP) chimeras, constituted
      of sequential PNA, DNA and PNA stretches, are potent decoy molecules in vitro.
      Interestingly, PDP-based decoys a) are more soluble than PNAs, b) are more
      resistant than synthetic oligonucleotides to enzymatic activity present in
      cellular extracts and serum and c) can be delivered with liposomes. In the
      present study we demonstrated that double-stranded PNA-DNA-PNA chimeras targeting
      NF-kappaB transcription factors induce apoptosis of human primary osteoclasts.
      Our data suggest that PDP-based induction of osteoclast apoptosis could be a
      therapeutic approach for disorders in which bone resorption is inappropriately
      excessive.

PMID- 15254757
TI  - Targeting Ku protein for sensitizing of breast cancer cells to DNA-damage.
AB  - Targeting molecular components that are critically involved in the maintenance of
      genome stability is a promising approach for overcoming intrinsic tumor cell
      resistance to DNA-damaging treatments. In mammalian cells, the Ku-dependent non
      homologous end-joining repair pathway is the predominant process for the repair
      of double-strand breaks (DSBs) in DNA. Previously, RNA aptamers were selected to
      efficiently block DNA-binding activity of the Ku protein in vitro. In the present
      study, we have tested the efficacy of RNA aptamers against the Ku protein as
      molecular sensitizer of MCF-7 breast carcinoma cells to DNA-damage. Toward this
      end, we established MCF-7 cell sublines stably expressing SC4 aptamer RNAs under
      the control of the human 7SL small nuclear RNA gene promoter. Vector-transfected
      (MCF/7SL) cells and cells stably expressing SC4 aptamers (MCF/SC4) were exposed
      to the anticancer drug etoposide and cellular responses to DNA-damage were
      evaluated. We found that the presence of RNA aptamers against Ku protein enhanced
      etoposide-induced growth inhibition of MCF-7 breast cancer. The SC4 aptamer
      mediated sensitization of MCF-7 cells to the anticancer drug is attributable to
      an increased susceptibility of these cells to apoptosis. The observed effects
      cannot be accounted for by the differential expression levels of Ku protein in
      control and SC4 aptamer-expressing cells, but are rather due to augmented DNA
      binding-capacity of Ku protein, as demonstrated in in vitro studies. Thus, RNA
      aptamers against Ku protein show potential to sensitize MCF-7 breast carcinoma
      cells to DNA-damaging agents.

PMID- 15254758
TI  - Phospholipase-C beta1 is predominantely expressed in the granular layer of rat
      cerebellar cortex.
AB  - The beta1 isoform of phospholipase-C is exclusively present in the nucleus of
      several hematopoietic and non-hematopoietic cell lines and primary cells of
      different species. When present, it represents the key enzyme for initiating the
      nuclear phospholipid breakdown that is involved in the cellular response to
      proliferating and differentiating stimuli. We have studied the expression of this
      enzyme isoform in the rat cerebellar cortex. We demonstrate that phospholipase-C
      beta1 (PLCbeta1) is predominantly expressed in the neurons of the granular layer,
      while it is virtually absent in the molecular and Purkinje cell layers of rat
      cerebellar cortex. This pattern of expression is partially different from that of
      the mouse cerebellar cortex, where not only granular cells, but also Purkinje
      cells express PLCbeta1. The high level of synaptic inputs that converge on
      granular cells may imply a constantly active nuclear phospholipid metabolism that
      may not be strictly required for the appropriate cellular responses of the other
      cell types of rat cerebellar cortex.

PMID- 15254759
TI  - Effect of ghrelin on the apoptotic deletion rate of different types of cells
      cultured in vitro.
AB  - Evidence indicates that ghrelin, an endogenous ligand of the growth hormone
      secretagogue receptor, controls the growth of several human and rat cell types
      cultured in vitro. Hence, we have investigated, by using both TUNEL and ELISA
      assays, the effects of 10(-8) M ghrelin on the basal apoptotic deletion rate of
      rat osteoblasts and thymocytes, rat and human adrenocortical cells, human
      umbilical vein endothelial cells, and human aldosteronoma cells cultured in
      vitro, as well as of the human adrenocortical carcinoma-derived cell lines NCI
      H295 and SW-13. Both assays consistently showed that ghrelin did not affect
      apoptotic rate of normal rat and human cells, but significantly enhanced
      apoptotic deletion in aldosteronoma, NCI-H295 and SW-13 cell cultures. Due to the
      central role of apoptosis in the control of tumor growth, these findings, if
      confirmed in other tumor cell types, could suggest an antitumoral action of
      ghrelin.

PMID- 15254760
TI  - Ubiquitous p63 expression in human esophageal squamous cell carcinoma.
AB  - p63, a recently identified member of the p53 gene family, plays an important role
      in human tissue functions. We examined the pattern of p63 expression in human
      esophageal squamous cell carcinomas including early-stage cancers, and its
      clinicopathological significance. Immunoreactivity for p63 was detected in 96.9%
      (63/65) esophageal squamous cell carcinomas. Diffuse p63 expression was seen in
      75.4% (49/65). p63 was detected not only in the in situ carcinomatous components
      or intramucosal carcinomas, but also in the invasive carcinomatous parts of the
      p63-positive cases. There were no significant correlations between p63 expression
      and clinicopathological features, such as depth of tumor invasion, tumor
      differentiation, lymph node metastasis and venous/lymphatic invasion. We also
      analyzed the relationship between p63 and p53 expression in esophageal squamous
      cell carcinomas. These results suggest that the p63 gene, as well as the p53
      gene, play a major role in the carcinogenesis of human esophageal squamous cells
      and in the growth of the carcinoma.

PMID- 15254761
TI  - The Na+/H+ exchange inhibitor HOE642 prevents stress-induced epithelial barrier
      dysfunction.
AB  - Recently, evidence has been obtained that the Na+/H+ exchange (NHE) inhibitor
      HOE642 may stabilize endothelial and epithelial barrier function in vivo.
      However, the underlying mechanisms are not known. Therefore, we studied the
      influence of HOE642 on the barrier function of the epithelial cell line CaCo2.
      The phorbolester phorbol 12-myristate 13-acetate (PMA) was used to induce
      hyperpermeability of the epithelial layer which was indirectly determined by
      measuring the transepithelial electrical resistance (TER). Confocal laser scan
      microscopy (LSM) served to analyze the intracellular localization of adherens and
      tight junction molecules. In five independent experiments we found that HOE642
      increased TER in non-treated CaCo2 cells (control: 350 +/- 28 Omega/cm2; HOE642:
      444 +/- 53 Omega/cm2) and prevented PMA-induced barrier dysfunction (PMA: 33 +/-
      12 Omega/cm2; PMA plus HOE642: 496 +/- 47 Omega/cm2). LSM showed that HOE642
      prevented the PMA-induced disassociation of the zonula adherens molecule beta
      catenin from the cell membrane and the decreased expression of the zonula
      occludens molecule ZO-1. From our data we conclude that HOE642 may prevent stress
      induced epithelial dysfunction by stabilization of cell membrane-associated
      junction molecules.

PMID- 15254762
TI  - Expression of CD34-positive sinusoidal endothelial cells in patients with HBV
      associated chronic liver diseases.
AB  - It has been demonstrated that CD34-positive cells isolated from human peripheral
      blood differentiate into endothelial cells and contribute to neoangiogenesis in
      adults. We investigated the role of CD34-positive endothelial cells in liver
      samples from patients with hepatitis B virus (HBV)-associated chronic liver
      diseases. Tissue sections were obtained by liver biopsy from 25 patients with HBV
      associated chronic liver diseases and were examined by immunohistochemistry using
      anti-CD34, anti-von Willebrand factor (vWF), and anti-vascular endothelial growth
      factor (VEGF) antibodies. CD34-positive, but vWF-negative endothelial cells were
      observed, particularly in the sinusoids and vascular endothelial cells. We
      counted these cells and expressed the results as a CD34-labeling index (LI). The
      CD34 LI did not correlate with VEGF expression and the CD34 LI of patients who
      progressed to hepatocellular carcinoma (HCC) tended to increase compared to those
      that did not progress to HCC. CD34 LI was an independent risk factor for
      development of HCC (relative risk, 35.689; P = 0.033). We conclude that CD34
      positive endothelial cells in patients with HBV-associated chronic liver diseases
      might play a role in hepatocarcinogenesis.

PMID- 15254763
TI  - The relationship of the human glutathione S-transferase P1 polymorphism and
      chemotherapeutic sensitivity in head and neck squamous carcinoma.
AB  - GSTP1, which encodes GSTPi, has a polymorphic site at codon 105 (exon 5), where
      an adenosine-to-guanine (A-G) transition causes an isoleucine-to-valine
      substitution (I105V). Recent studies have found that subjects with the valine
      allele display a significantly lower enzyme activity and less effective
      capability of detoxification. We hypothesized that head and neck squamous cell
      carcinoma (HNSCC) might respond differently to chemotherapeutic agents,
      especially cisplatin (CDDP) because of the presence of GSTP1 I105V polymorphism.
      Seventeen types of HNSCC cell lines were investigated with the MTT method,
      western blot, RT-PCR and direct sequence to examine the relationship between the
      sensitivity to CDDP and expression of GSTPi. There was a significant degree of
      difference in cell death among each cell line in the sensitivity test with CDDP,
      however, we did not find differences in the band density of the protein and mRNA
      expression levels of GSTPi. In the direct sequence examination we detected 4
      subjects heterozygous of polymorphism GSTP1. The frequency was 23.5% in the 17
      cell lines examined, and all 4 subjects showed a good response to CDDP treatment.
      A heterozygous polymorphism might alter the function of the GSTPi due to
      significantly lower enzyme activity and less effective capability of
      detoxification. Two other subjects which showed a good response to CDDP treatment
      did not show any polymorphism. These results indicated that there is another
      locus that reduces GSTPi activity, and that the mechanisms of CDDP resistance was
      multifactorial. Further study is required to conclude whether the GSTP1 I105V
      polymorphism might be useful as a predictive marker for multi-drug resistance.

PMID- 15254764
TI  - Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin
      6-deficient mice.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine secreted by various cells, and
      is involved in the acute phase response and the immune response through T and B
      cell activation. To further define the role of IL-6 in intestinal inflammation,
      we studied the effects of dextran sulfate sodium (DSS) administration in mice
      with targeted deletions of the IL-6 gene. Acute colitis was induced in female IL
      6-/- and IL-6+/+ mice by giving 4.5% DSS orally in drinking water for 8 days. The
      colonic mucosal injury and inflammation was evaluated based on survival rate,
      body-weight changes, total colon length and histological findings. Colonic mRNA
      expression for tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and inducible
      nitric oxide synthase (iNOS) was measured by RT-PCR. Colonic IL-6 mRNA levels of
      wild-type mice continued to increase throughout the study period. At each
      assessment, colonic injury was significantly attenuated in DSS-treated IL-6-/-
      mice compared with DSS-treated IL-6+/+ mice. Histological study also showed a
      reduced infiltration of inflammatory cells, especially neutrophils, and mucosal
      cell disruption in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+
      mice. In the colons of DSS-treated IL-6-/- mice, the expression of both TNF-alpha
      mRNA and iNOS mRNA was reduced on day 5. In contrast, IL-10 mRNA expression was
      enhanced compared with DSS-treated IL-6+/+ mice. In conclusion, DSS-induced
      inflammation appears to be significantly inhibited in IL-6-/- mice compared to
      wild-type mice. These data suggest that persistent and marked blockade of IL-6
      bioactivity provides some beneficial effects on intestinal inflammation.

PMID- 15254765
TI  - Lysosomal dysfunction on hydrogen peroxide-induced apoptosis of osteoarthritic
      chondrocytes.
AB  - The purpose of this study was to examine the mechanism of hydrogen peroxide
      induced apoptosis in osteoarthritic chondrocytes. We evaluated the reactive
      oxygen species (ROS) formation, lysosomal staining and dysfunction of the
      mitochondrial membrane potential in these cells after exposure to hydrogen
      peroxide. Osteoarthritic chondrocytes were isolated, and divided into 4 dishes in
      which different concentrations (0.1 mM, 1 mM and 10 mM) of hydrogen peroxide, or
      no additive (control) was added. The cells were incubated for 1 or 4 h, then
      assayed for ROS formation, mitochondrial membrane potential and lysosomal
      staining. ROS formation was detected in chondrocytes after 1 h of exposure to
      hydrogen peroxide concentrations over 0.1 mM. Lysosomal swelling was detected
      after 1 h of exposure to hydrogen peroxide concentrations of 0.1 mM and over,
      possibly revealing lysosomal membrane instability. Moreover, indications of
      lysosomal rupture, including release of lysosomal enzymes, were apparent 1 h
      after addition of 10 mM of hydrogen peroxide. The addition of hydrogen peroxide
      to chondrocytes induces ROS formation and lysosomal dysfunction, revealed by
      swelling and rupture, prior to dysfunction of the mitochondrial membrane
      potential. Anti-oxidants may have a therapeutic application in the prevention of
      lysosomal dysfunction to inhibit chondrocyte apoptosis and degradation of the
      cartilage matrix.

PMID- 15254766
TI  - Development of pancreatic islets in pancreatic polypeptide-overexpressing mice.
AB  - Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that
      PP was overexpressed in pancreatic islets. The present study examines development
      of four islet hormones in PPTG mice at embryonic days (ED) 15, 17, and 19, and in
      adult animals. Adult PPTG mice showed massive aggregation of PP-positive cells
      and glucagon-positive cells seen at the central area of the islets. Confocal
      laser microscopic study showed that three islet hormones (insulin, glucagon and
      PP) were completely overlapped in islets of PPTG mice. Overlapping of
      somatostatin/glucagon and somatostatin/PP were also increased at the peripheral
      area of the islets in adult PPTG mice compared to wild-type mice. In prenatal
      development of pancreatic islets of PPTG mice, somatostatin/glucagon overlapping
      cells appeared at ED 15, two days earlier than in wild-type mice. Differentiation
      of these somatostatin/glucagon double-positive cells into single-positive cells
      was disturbed in the PPTG mice during perinatal to postnatal periods.
      Differentiation of glucagon/insulin-double positive cells into single-positive
      cells was disturbed remarkably in postnatal development of the islets of PPTG
      mice. The present results suggest that early and overexpression of PP may
      engender the early appearance of somatostatin producing cells; however, that may
      disturb differentiation of multihormonal immature endocrine cells into single
      hormonal mature endocrine cells.

PMID- 15254767
TI  - Induction of polycystic ovary by testosterone in immature female rats: Modulation
      of apoptosis and attenuation of glucose/insulin ratio.
AB  - Polycystic ovarian syndrome is seen in 5% of fertile aged women. However, there
      is no satisfactory PCOS model in experimental animals. To induce polycystic ovary
      phenotype in immature female rats, Wistar rats 21 days of age were injected daily
      with testosterone propionate 1 mg/100 g body weight dissolved in propylene glycol
      or propylene glycol for up to 35 days. Seven days of injection with testosterone
      (T) resulted in the appearance of large cystic follicles and a dramatic
      accumulation of multi-layer preantral follicles. At 42 days of age puberty in
      control animals was evident by the appearance of corpora lutea. In contrast in T
      treated animals no corpora lutea formation was seen even at the age of 56 days.
      Progesterone in the control animals was elevated at the age of 42 days in
      contrast with the T treated animals in which progesterone remained low (20% of
      control). While during 14 days of T injection most of the follicles did not have
      progressive apoptosis, at 21-35 days of injection (42-56 days of age) the vast
      majority of follicles became apoptotic. Progressive degeneration of oocytes was
      evident in T treated animals reaching 70-85% of total oocytes at 21-35 days of T
      injection compared to 30-40% in control animals. Western blot analysis of ovarian
      homogenates revealed gradual decrease in Bcl-2 content, evident at 28 and 35 days
      of T injection compared to control animals. Interestingly, the fasting
      glucose/insulin ratio was dramatically reduced in T treated animals following 14
      days of testosterone treatment compared to controls. Our data suggest that T
      injection to immature female rats can induce polycystic ovaries, block ovulation
      and attenuate progesterone production. Moreover, normal/low glucose and high
      insulin blood levels in the testosterone treated rats raises the possibility that
      elevated androgens can lead to insulin resistance in this experimental PCOS
      model.

PMID- 15254768
TI  - Identification of genes differentially expressed in breast cancer cell line
      SKBR3: potential identification of new prognostic biomarkers.
AB  - The identification of differentially expressed genes in tumour cells should have
      important implications in understanding carcinogenesis and developing new
      therapeutic and prognostic biomarkers. We have combined PCR-based cDNA
      subtraction and Northern blotting to identify truly differentially expressed
      genes in breast cancer cell line SKBR3 as compared to normal human mammary
      epithelial cells (HMEC). Hybridizing probe molecules were rescued from the Hybond
      N+ membranes and then PCR reamplified. The PCR reamplification is possible due to
      the fact that all probe molecules contain the same pair of adapter sequences on
      both ends. After cloning and sequencing three known genes, ribosomal protein L19
      (RPL19), ADP/ATP carrier protein and ErbB-2 with high-elevated mRNA levels in
      SKBR3 were identified. In addition, two overexpressed genes with unknown
      functions, CXYorf1-related protein and hypothetical protein PRO2605, were found.
      High-titer andibodies against the recombinant RPL19 were detected in 5 patients
      out of 50 patients investigated. Thus, the present novel strategy based on the
      combination of PCR-based cDNA subtraction and Northern blotting should facilitate
      the identification of truly differentially expressed biomarkers, which may offer
      the potential to determine the proper drug for an individual patient at a given
      stage of disease or treatment.

PMID- 15254769
TI  - Cellular analysis of growth suppression induced by the Notch ligands, Delta-1 and
      Jagged-1 in two myeloid leukemia cell lines.
AB  - It is known that Notch activation promotes the self-renewal of hematopoietic
      cells. However, we have previously found that the growth of a myeloid leukemia
      cell line, OCI/AML-6, was suppressed by Notch activation induced by stimulation
      with a recombinant Notch ligand, Delta-1 protein. We recently found that the
      growth of another leukemia cell line, THP-1, was also suppressed by the ligands
      Delta-1 and Jagged-1. In this study, we tried to clarify the cellular and
      molecular mechanism of the growth suppression induced by Notch activation. Flow
      cytometric analysis showed that Delta-1 stimulation increased the expression of
      differentiation markers such as CD11b and CD13 while it decreased the expression
      of CD117 (c-KIT), a marker for primitive cells in THP-1 cells. In OCI/AML-6
      cells, Delta-1 stimulation decreased the expression of CD11b and CD14 and
      increased CD34 expression. Namely, Delta-1 showed the opposite effects on the
      differentiation markers of each cell line. Delta-1 stimulation did not increase
      the binding of annexin V, a marker for apoptotic cells in either cell line. Since
      the growth of myeloid cells is regulated by MAP kinase and JAK/STAT pathways, we
      investigated the effects of the ligand stimulation on these pathways. Delta-1
      stimulation did not induce the phosphorylation of ERK1/2 and STAT3 proteins in
      either cell line. Pre-exposure to Delta-1 did not affect the phosphorylation of
      ERK1/2 and STAT3 induced by G-CSF in OCI/AML-6 cells, either. Namely, it is
      thought that these pathways are not involved in the growth suppression caused by
      Notch ligands. Our study revealed several findings on Notch function. However,
      the precise mechanism remains to be elucidated.

PMID- 15254770
TI  - Induction of apoptotic cell death by mycelium extracts of Phellinus linteus in
      human neuroblastoma cells.
AB  - Phellinus linteus is a well-known Oriental medicinal fungus that has various
      biological activities, including immunomodulatory and anti-tumor activities, the
      mechanisms of which are poorly understood. In the present study, we investigated
      the effects of mycelium extracts of P. linteus (MEPL) on the growth of human
      neuroblastoma SK-N-MC cells. Upon treatment with MEPL, a concentration-dependent
      inhibition of cell proliferation was observed and cells developed many of the
      hallmark features of apoptosis, including condensation of chromatin and an
      increase in the sub-G1 population. The anti-proliferative and apoptotic effects
      of MEPL were associated with a marked induction of the Bax and cyclin-dependent
      kinase inhibitor p21. Western blotting and in vitro caspase-3 activity assay
      demonstrated that the processing/activation of caspases accompanies the
      generation of MEPL-mediating apoptotic cell death. In addition, the proteolytic
      cleavage of specific target proteins such as poly(ADP-ribose) polymerase and beta
      catenin were observed. Taken together, the present results suggest that apoptotic
      signals evoked by MEPL in human neuroblastoma SK-N-MC cells may converge caspase
      3 activation through an up-regulation of Bax rather than a down-regulation of Bcl
      2.

PMID- 15254771
TI  - Substrate specificity of Xenopus matrix metalloproteinase stromelysin-3.
AB  - The matrix metalloproteinase stromelysin-3 (ST3 or MMP11) was initially
      identified as a breast carcinoma associated protease and has since been shown to
      be highly expressed in diverse carcinomas and in developmental processes that
      involve extensive cell death (apoptosis) and tissue remodeling. Unlike other
      MMPs, purified ST3 has little activity toward known extracellular matrix (ECM)
      proteins in vitro but cleaves strongly a few non-ECM, extracellular proteins,
      including human alpha1-proteinase inhibitor (alpha1-PI). To investigate the
      possibility of alpha1-PI as a conserved physiological substrate for ST3 during
      vertebrate development, we analyzed the ability of Xenopus laevis ST3 catalytic
      domain to cleave frog alpha1-PI. Surprisingly, we found the ST3 failed to
      recognize the site in alpha1-PI equivalent to the major cleavage site in human
      alpha1-PI by mammalian ST3. Sequence and mutagenic analysis revealed that
      multiple substitutions at P2-P3' positions between human and Xenopus alpha1-PI
      contributed to the inability of Xenopus alpha1-PI to be cleaved by ST3. Our
      studies showed that (A)(G/A)(A)(M)(F/A)(L) (P3-P3') as a preferred cleavage site
      for ST3. We further demonstrated that mutations in the cleavage sites affected
      cleavage by ST3 differently from several other MMPs. These findings, together
      with earlier reports on ST3, showed that ST3 has distinct substrate specificities
      compared to other MMPs. Our results further suggest that alpha1-PI is unlikely to
      be a physiological substrate for ST3, at least with regard to evolutionarily
      conserved developmental processes.

PMID- 15254772
TI  - Role of caspase in CD80 expression of superantigen-stimulated monocytes.
AB  - In this study, we demonstrated evidence for the induction of CD80+ monocytes by
      staphylococcal enterotoxin B (SEB) via caspase actions. Pre-treatment with
      pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB, resulted in
      a significant reduction in the percentage of SEB- and interferon-gamma (IFN
      gamma) (produced by SEB) -induced CD80+ monocytes. SEB and IFN-gamma activated NF
      kappaB, which was inhibited by PDTC. SEB induced the activation of caspase-3 and 
      8, and pre-treatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases,
      prevented the induction of apoptosis. Treating with z-VAD-fmk resulted in a
      reduction of the generation of CD80+ monocytes. These results indicated that CD80
      driven by NF-kappaB is regulated by the enzymatic actions of caspases, which
      allows monocytes to participate in massive T-cell activation.

PMID- 15254773
TI  - Dynamics and regional distribution of c-fos protein expression in rat brain after
      a closed head injury.
AB  - The objective of this study was to define the time- and brain-area-related
      distribution of c-fos expression in the brain during the first 24 h following a
      closed head injury in rats. In the control groups (n = 32), only a few c-fos
      positive nuclei were observed in the brain and the c-fos staining did not change
      during the next 24 h. In the closed head injury group c-fos-positive cells were
      rare in the brain regions during the first 30 min. During the next 2 h, the
      number of c-fos-positive cells increased rapidly in the basal ganglions, the
      ventricular ependyma cells the corticospinal tract, the area postrema, the
      cerebral neocortex, and the corpus callosum. The increase was highest in the
      corpus callosum (317 +/- 44.5 mm(-2)), in the thalamic reticular nucleus (474.8
      +/- 49.2 mm(-2)), in the dentate hilus (1090 +/- 187 mm(-2)) and in the cerebral
      neocortex (992 +/- 93 mm(-2)). Thereafter, the elevated c-fos expression
      gradually decreased and at 6 h post-closed head injury no significant differences
      were observed between the controls and the trauma group. We conclude that a
      closed head injury induces a large, transient increase of c-fos expression in the
      brain. Since the observed time course and regional differences in c-fos
      expression are in good agreement with the cognitive and memory deficits observed
      after human TBI it can be utilized in further investigations, especially to test
      the effects of various forms of pharmacological or cellular therapy.

PMID- 15254774
TI  - Induction of apoptosis by ar-turmerone on various cell lines.
AB  - This study investigated the cytotoxic effect of ar-turmerone isolated from
      turmeric (Curcuma longa L) on the K562, L1210, U937 and RBL-2H3 cell lines by the
      MTT assay. Ar-turmerone exhibited potent cytotoxicity on these cancer cell lines.
      The IC50 values of ar-turmerone on these cell lines were 20-50 microg/ml. They
      showed an increased inhibition ratio on cell viability according to the drug
      concentration < or = 80 microg/ml in the cell lines tested. The DNA fragmentation
      that is a characteristic of apoptosis due to ar-turmerone occurred in a
      concentration- and time-dependent manner in the K562, L1210, U937 and RBL-2H3
      cancer cell lines. These results suggest that ar-turmerone can induce the
      apoptotic activity in the K562, L1210, U937 and RBL-2H3 cells.

PMID- 15254775
TI  - Development and characterization of five cell models for chemoresistance studies
      of human ovarian carcinoma.
AB  - Platinum agents and paclitaxel (taxol) are among the most effective drugs
      currently available for treatment of ovarian cancer. One of the hurdles with
      taxol and platinum- based therapy is the clinical development of resistance to
      these agents. To investigate the mechanism of drug resistance in human ovarian
      cancer, we developed and characterized 5 cell models for chemoresistance studies
      of cisplatin, carboplatin and taxol. We report in this study that these human
      ovarian carcinoma cell model systems include 2 models for cisplatin resistance, 2
      models for carboplatin resistance, and 1 model for taxol resistance. The
      biological and biochemical characteristics of the models showed that (i), the
      IC50 values of the drugs for all these resistant cell models were 3 times (or
      more) higher than those for the parental tumor cells. There also exist varying
      degrees of cross-resistance to several other chemotherapeutic agents in these
      systems. Moreover, the intracellular drug accumulations in these cells were
      significantly reduced as compared to those in the parental cells. (ii), The
      proliferation rates of these resistant cells were markedly decreased. However,
      there were no obvious changes in cell cycle distribution in these model systems.
      (iii), Our results for the expression of a few major drug resistance-related
      genes revealed that the expression of p53, lrp-1 and mrp-1 was decreased, while
      the expression of pkc, topo I and topo II beta was increased in the resistant
      tumor cells as compared with the parental cells. In contrast, no significant
      alterations in gst-pi and topo II alpha expression were found. Interestingly, the
      levels of mdr-1 expression were elevated in some models, but were reduced in
      others, thus suggesting that different pathways are involved in the formation of
      drug resistance in different cell model systems, and that different mechanisms
      are responsible for the development of different drug resistances in tumor cells.
      Taken together, our findings indicate that these models may be potentially used
      to assess the biochemical and genetic mechanisms of drug resistance in human
      ovarian cancer and to identify new drug resistance-related genes.

PMID- 15254776
TI  - Early graft hemodynamics in living related liver transplantation evaluated by
      Doppler ultrasonography.
AB  - The aim of this study was to clarify the perioperative hemodynamics of liver
      grafts without vascular complications during and early after liver
      transplantation from living donors. This study was carried out in 4 child
      recipients (lateral segment left lobe grafts) and 6 adult recipients (right lobe
      grafts) of liver transplantation from living donors. The hemodynamics of the
      hepatic artery, portal vein, and hepatic vein of the grafts during and until 7
      days after surgery were studied by Doppler ultrasonography. The maximum flow
      velocity of the hepatic artery, mean portal blood flow velocity, and pulsatility
      index (PI) of the hepatic artery increased in all 10 grafts with no vascular
      complication after vascular anastomosis. After surgery, the mean portal blood
      flow velocity showed a peak 3 days after surgery and reached a nadir 7 days after
      surgery in both the lateral segment left lobe grafts in children and the right
      lobe grafts in adults, but it was significantly higher in the right lobe grafts
      in adults (mean +/- SD 31.0 +/- 6.3 vs. 22.4 +/- 0.9 cm/sec). Also, as the
      hepatic artery blood flow velocity increased the portal blood flow velocity
      decreased, the hepatic blood flow during liver regeneration was suggested to be
      controlled by both the artery and portal vein. The range of PI of the hepatic
      artery was 0.60-1.86. The mean hepatic venous blood flow was stable throughout
      the observation period (30.4 +/- 8.8 cm/sec). Although the hepatic venous flow
      waves changed widely from pulsed waves to a flat flow, its changes did not
      suggest a vascular complication. Evaluation of changes by Doppler ultrasonography
      in the hemodynamics of the liver grafts without vascular complications during and
      early after liver transplantation from living donors is considered to be useful
      for accurate monitoring of the hemodynamics during liver regeneration and early
      detection of abnormalities.

PMID- 15254777
TI  - Adenoviral-mediated transfer of p53 gene enhances TRAIL-induced apoptosis in
      human hepatocellular carcinoma cells.
AB  - p53 is a tumor suppressor protein with numerous biological functions including
      transformation, regulation of cell growth, differentiation and apoptosis. The TNF
      related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various
      transformed cell lines. We investigated the effects of combining wild-type p53
      gene transduction by adenoviral infection (Ad-p53) with addition of TRAIL on cell
      death, expression levels of TRAIL receptors (TRAIL-R1, TRAIL-R2), FLICE
      inhibitory protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) on
      human hepatocellular carcinoma (HCC) cell lines. HCC cell death was increased by
      combination of Ad-p53 infection and addition of TRAIL compared to either alone.
      Western blotting demonstrated decreased TRAIL-R1 and TRAIL-R2 levels after
      infection with Ad-p53. FLIP levels decreased in Huh7 cells and Hep3B cells, and
      XIAP levels decreased in all three HCC cell lines after infection with Ad-p53.
      Thus, death of HCC cells due to combined p53 gene transduction and exogenous
      TRAIL may be due to down regulation of FLIP or XIAP.

PMID- 15254778
TI  - Role of regucalcin in liver nuclear function: binding of regucalcin to nuclear
      protein or DNA and modulation of tumor-related gene expression.
AB  - Regucalcin is a regulatory protein in the intracellular signaling pathway which
      is related to regulation of nuclear function. In this study the binding of
      regucalcin to nuclear proteins or DNA in vitro was examined. The results of the
      Far-Western analysis showed the existence of protein components which bind to
      regucalcin in the nucleus isolated from rat liver. Whether regucalcin binds
      deoxyribonucleic acid (DNA) was analyzed using DNA cellulose in vitro. Regucalcin
      was incubated in reaction mixture containing DNA cellulose, and DNA-binding
      regucalcin was detected using Western blot analysis for regucalcin. The results
      showed that regucalcin binds DNA in vitro. Moreover, the expression of c-src,
      p53, and Rb mRNAs was examined in the cloned rat hepatoma H4-II-E cells cultured
      for 24 or 48 h in the presence of fetal bovine serum (10%), using reverse
      transcription-polymerase chain reaction (RT-PCR). The expression of oncogene c
      src mRNA was significantly suppressed in the hepatoma cells (transfectants),
      overexpressing regucalcin. Meanwhile, the expression of the tumor suppressor gene
      p53 or Rb mRNA was significantly enhanced in transfectants. This study may
      support the view that regucalcin modulates the transcriptional process by binding
      to protein and DNA in the nucleus.

PMID- 15254779
TI  - Influence of DMBA-induced mammary cancer on the liver CPT I, mit HMG-CoA synthase
      and PPARalpha mRNA expression in rats fed a low or high corn oil diet.
AB  - Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I) and
      mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) enzymes
      play a key role in regulation of fatty acid oxidation and in ketogenic pathways,
      respectively. Their expression are regulated by fatty acids mainly by the
      peroxisome proliferator-activated receptor alpha (PPARalpha). To investigate
      possible mechanisms through which cancer alters the lipid metabolism, we analyzed
      by Northern blot, the mRNA relative abundance of these proteins in liver from
      healthy and DMBA-induced mammary tumor-bearing rats fed a low or high corn oil
      diet. Serum levels of lipids, body weight and mass were also determined. Whereas
      mRNA steady-state levels of CPT I and mit HMG-CoA synthase were unaffected by the
      presence of the extra-hepatic tumor, the cancer state seemed to modify the
      regulation of the expression of these genes by high fat diet. We hypothesize that
      putative changes in PPARalpha mRNA levels could have contributed to such
      alterations. These results, together with changes in serum lipid profiles, body
      weight and mass, indicate fat mobilization and non-enhanced oxidation rates
      despite a high-fat feeding. This effect of the cancer state could be related to
      tumor aggressiveness and suggest a preferential redirection of long-chain fatty
      acids into energetic and specific pathways of the cancer cells.

PMID- 15254780
TI  - CpG methylation of the ERalpha and ERbeta genes in breast cancer.
AB  - Aberrant methylation of promoter CpG islands is known to be responsible for the
      alteration and silencing of genes in cancer. The data presented here describes
      that the CpG methylations of ERalpha and ERbeta are found in breast cancer
      tissues, and methylation exerts a considerable effect on gene silencing,
      investigated by bisulfite genomic sequencing and reverse transcriptase polymerase
      chain reaction. Consequently, hypermethylation of the ERalpha and ERbeta genes
      was found in 66.0% and 50.0% of 50 breast cancers, respectively. Eleven of 50
      samples (22.0%) did not show any methylation of either ERalpha or ERbeta, whereas
      19 samples (38.0%) showed methylation of both ERalpha and ERbeta. The tumors that
      showed aberrant methylation of ERalpha and ERbeta did not express mRNA, compared
      with unmethylated cases (p < 0.01). The methylated case was negatively correlated
      with the expression of the ERalpha protein (p < 0.01). In addition, ERbeta
      methylation demonstrated significant associations with the lower level of Ki67
      (9.36 +/- 2.43 versus 19.68 +/- 3.42, p = 0.02). Although the number of samples
      was relatively small, our results suggest that DNA methylation in ERalpha and
      ERbeta are present in breast cancer tissue, and that the methylation causes a
      significant effect on transcriptional silencing. Furthermore, the CpG methylation
      of the ERbeta gene seems to play a role in cell proliferation of breast cancer
      tissue.

PMID- 15254781
TI  - Production and efficacy of a dendritic cell-based therapeutic vaccine for murine
      chronic hepatitis B virus carrierer.
AB  - Recently a new field of immunological research and clinical application of
      vaccines for therapeutic purposes (vaccine therapy) has been developed for
      treating several chronic viral infections including chronic hepatitis B virus
      (HBV) infection. Administration of vaccine containing hepatitis B surface antigen
      (HBsAg) for 1 year has resulted in negative HBsAg and development of antibody to
      HBsAg (anti-HBs) in some, but not in all, HBV transgenic mouse (HBV-Tg). In order
      to develop more potent regimen of vaccine therapy for chronic HBV carrier, we
      prepared a dendritic cell (DC)-based therapeutic vaccine and evaluated their
      therapeutic potential in HBV-Tg. DCs were isolated from single cell suspensions
      of murine spleen cells by collagenase digestion, density centrifugation and
      depletion of lymphocytes. Spleen DCs were cultured with HBsAg (100 microg) for 24
      h to produce HBsAg-pulsed DCs. HBV-Tg expressing HBsAg and HBV DNA in the sera
      were randomly assigned to receive either HBsAg-pulsed DCs (n = 20) or unpulsed DC
      (n = 20) or vaccine containing HBsAg (n = 39) or complete Freund's adjuvant (n =
      20) or left untreated (n = 20). Only two intraperitoneal injections of HBsAg
      pulsed DCs resulted in negative HBsAg and production of anti-HBs in the sera in
      all HBV-Tg (n = 20). However, administration of un-pulsed DCs (n = 20) or vaccine
      containing HBsAg (n = 39) or only complete Freund's adjuvant did not induce
      negative HBsAg or production of anti-HBs in any HBV-Tg within 6 months of therapy
      commencement. Taken together, this study showed that HBsAg-pulsed DCs represent a
      highly potent therapeutic vaccine for chronic HBV infection and inspire optimism
      of using this vaccine in clinical conditions. A clinical trial of HBsAg-pulsed DC
      in patients with chronic hepatitis B is warranted.

PMID- 15254782
TI  - Distribution of HBV genotypes and mutants among hepatitis B infected patients
      from northern Poland.
AB  - Hepatitis B virus (HBV) infection is one of the major global epidemiological
      problems. The aim of our study was to determine the distribution of HBV genotypes
      in Poland since the data concerning the spread of HBV viruses in the central
      eastern region of Europe is still very limited. HBV DNA was extracted from 58
      serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor
      Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were
      performed. The HBV virus from 43 serum samples from hepatitis B infected patients
      was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in
      Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg
      sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype
      A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and
      equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most
      prevalent subtype in the Amerindians. Our results coincide with the general
      European HBV prevalence. However, HBV genotype F, which is not a common genotype
      in European countries, was detected and so was relatively high occurrence of
      genotype D, which may reflect historical and ethnical migration events in Poland
      in the past.

PMID- 15254783
TI  - Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic
      acid is enhanced in combination with caffeic acid.
AB  - We investigated a possible enhancement of all-trans retinoic acid (ATRA)-induced
      differentiation of HL-60 human myeloid leukemia cells by caffeic acid (CA), a
      widely distributed plant phenolic compound. Our results showed that CA, in the
      concentration of 13 or 52 micro M, had no or minimal influence on cell
      differentiation, whereas the differentiating activity of ATRA was potentiated by
      CA treatment. We proved, using flow cytometric detection of the CD66b surface
      molecule, a synergistic effect of CA: at day 10, 18.3% of CD66b-positive cells
      were detected after treatment with ATRA only, and 33% when CA and ATRA were
      combined together. NBT-assay confirmed that this additive effect of CA on ATRA
      induced differentiation. Proliferating activity as assessed by MTT-assay was
      generally not affected by CA at given concentrations. However, cell proliferation
      was significantly reduced by 52 micro M CA at 96-h intervals. This effect was
      markedly enhanced when CA, at both concentrations, and ATRA were combined. The
      possibility to enhance the differentiation potential of ATRA by CA may improve
      outcomes in the therapy of acute promyelocytic leukemia.

PMID- 15254784
TI  - Hematological findings in SARS patients and possible mechanisms (review).
AB  - Severe acute respiratory syndrome (SARS) is a new human infectious disease. The
      causative agent of SARS is a novel coronavirus (SARS-CoV). This report summarizes
      the hematological findings in SARS patients and proposes the possible mechanisms
      of SARS-CoV related abnormal hematopoiesis. Hematological changes in patients
      with SARS are common and include lymphopenia, thrombocytopenia and occasionally
      leukopenia. A significant decrease was also observed in peripheral CD4+ and CD8+
      T lymphocyte subsets and it was related to onset of SARS. A number of potential
      mechanisms may be involved. The development of auto-immune antibodies or immune
      complexes triggered by viral infection may play a major role in inducing
      lymphopenia and thrombocytopenia. Moreover, SARS-CoV may also directly infect
      hematopoietic stem/progenitor cells via CD13 or CD66a inducing their growth
      inhibition and apoptosis. The receptor for group I and III CoV is aminopeptidase
      N (CD13). CD13 has been identified in human bone marrow CD34+ cells, platelets,
      megakaryocytes, myeloid cells, and erythroid cells, but not in lymphocytes. The
      common receptor for group II CoV is CEACAM1a (CD66a). CD66a is an adhesion
      molecule expressed on bone marrow CD34+ cells, platelets, granulocytes and
      activated lymphocytes. In addition, glucocorticoids could induce lymphopenia and
      the use of steroids may account for the decrease of lymphocytes in some SARS
      patients. The increased consumption of platelets and/or the decreased production
      of platelets in the damaged lungs are a potential alternative but often
      overlooked mechanism that can contribute to thrombocytopenia in severe critical
      pulmonary conditions.

PMID- 15254785
TI  - The pro- and anti-inflammatory markers in patients with acute myocardial
      infarction and chronic stable angina.
AB  - The aim of this study was to assess the plasma levels of VEGF and interleukin-10
      in patients with acute myocardial infarction (AMI) and stable chronic angina (SA)
      and correlate the values with traditional CHD risk factors, left ventricular
      ejection fraction (LVEF) and established inflammatory marker hsCRP. Fifty
      patients with AMI and 30 with SA were enrolled. IL-10 levels in AMI patients were
      lower than in SA patients (9.81 +/- 5.0 versus 22.63 +/- 8.38 pg/ml, p <
      0.00001). IL-10 levels were lower in AMI and SA patients with multiple CHD risk
      factors than in patients < or = 2 risk factors (SA: 19.48 +/- 2.94 versus 23.77
      +/- 2.94 pg/ml; p < 0.005; AMI: 8.64 +/- 4.43 versus 11.85 +/- 4.09 pg/ml; p <
      0.05) and patients with AMI and single-vessel than with multi-vessel disease
      (8.45 +/- 3.86 versus 10.72 +/- 3.95 pg/ml; p < 0.05). VEGF levels in AMI
      patients were higher than in SA patients (312.0 +/- 67.0 versus 221.0 + /- 50
      pg/ml; p < 0.005). VEGF levels were higher in AMI patients with multi-vessel
      disease than in patients with single-vessel disease (348.74 +/- 45.23 versus
      252.05 +/- 21.12 pg/ml; p < 0.005), with LVEF <40% and Killip class III-IV than
      in patients with LVEF >40% and Killip class I-II (338.8 +/- 51.59 versus 271.8 +/
      50.51 pg/ml; p < 0.005 and 340.71 +/- 52.94 versus 275.45 +/- 49.48 pg/ml; p <
      0.05, respectively) and with chest pain > 6 h versus < 6 h (330.03 +/- 58.58
      versus 292 +/- 57.53 pg/ml; p < 0.05). HsCRP concentrations in AMI patients were
      higher than in SA (1.24 +/- 0.47 versus 0.42 +/- 0.14; p < 0.0001). HsCRP was
      correlated with IL-10 (r = -0.413; p < 0.05) and VEGF (r = 0.319; p < 0.05).
      Acute myocardial infarction is associated with elevated VEGF levels and decreased
      concentration of IL-10. There is a significant correlation between levels of
      inflamatory markers and CHD risk factors and the function of the left ventricle
      on admission.

PMID- 15254786
TI  - Per os administration of 5-fluorocytosine is effective in the regression of CD
      expressing liver metastases in rats.
AB  - The bacterial cytosine deaminase (CD) gene, associated to the 5-fluorocytosine (5
      FC) prodrug, is one of the more widely used suicide systems in gene therapy.
      Introduction of the CD gene within a tumor induces, after 5-FC treatment of the
      animal, a local production of 5-fluorouracil (5-FU) resulting in intratumor
      chemotherapy. Destruction of the gene-modified tumor is then followed by the
      triggering of an anti-tumor immune reaction resulting in the regression of
      distant wild-type metastasis. In pre-clinical studies, 5-FC is generally
      administered by daily intraperitoneal injections. However, when used as an anti
      fungal in humans, either IV or oral administration is used. In this study, we
      compared oral and intraperitoneal 5-FC administration in rats bearing a wild-type
      and a cytosine deaminase-expressing liver tumors. The results indicate that per
      os 5-FC administration is as efficient as intraperitoneal for the induction of CD
      expressing tumor regression and the triggering of a distant bystander effect,
      acting on wild-type liver tumor and extra-hepatic metastasis.

PMID- 15254787
TI  - Identification and characterization of human FCHO2 and mouse Fcho2 genes in
      silico.
AB  - FNBP1, FNBP1L, CIP4/TRIP10, FNBP2, SRGAP1/ARHGAP13, SRGAP2/ARHGAP14, ARHGAP4,
      FCHSD1, and FCHSD2 constitute the FCFBS superfamily characterized by FES-CIP4
      homology (FCH) domain, Formin-binding FNBP1-FNBP2 homology (FBH) domain, and SRC
      homology 3 (SH3) domain. During genome-wide searching for human genes encoding
      FCH domain molecules, we identified the FCHO2 gene by using bioinformatics.
      DKFZp451B033 (AL831971.1) was the representative cDNA derived from human FCHO2
      gene, while FLJ32208 (AK056770.1) was a chimeric cDNA generated by the
      recombination between FCHO2 and CSH1 genes. MGC63242 (BC052456.1) rather than
      5832424M12 (AK031041.1) was the representative cDNA derived from mouse Fcho2
      gene. FCHO2 gene, consisting of 26 exons, was mapped to human chromosome 5q13.2.
      Human FCHO2 (810 aa) showed 94.6% total-amino-acid identity with mouse Fcho2 (809
      aa), and 50.4% total-amino-acid identity with human FCHO1. Drosophila CG8176
      (NP_788613.1) and C. elegans 2B609 (NP_493947.1) were homologs of mammalian FCHO2
      and FCHO1. FCHO-homologous (FOH) domain (codon 527-810 of human FCHO2) was
      identified as the novel domain conserved among FCHO homologs. Human FCHO2, FCHO1,
      Drosophila CG8176 and C. elegans 2B609 were found consisting of N-terminal FCH
      domain and C-terminal FOH domain. This is the first report on identification and
      characterization of evolutionarily conserved FCHO homologs as well as the novel
      FOH domain.

PMID- 15254788
TI  - Identification and characterization of ARHGAP24 and ARHGAP25 genes in silico.
AB  - RhoGAP family proteins, encoded by ARHGAP family genes, are negative regulators
      of Rho family GTPases, which are implicated in actin remodeling, cell polarity
      control, and cell migration. Based on the homology with ARHGAP22, we identified
      and characterized two novel ARHGAP family genes, ARHGAP24 and ARHGAP25. FLJ33877
      cDNA (AK091196.1) and aberrant DKFZp564- B1162 cDNA (NM_031305.1) were derived
      from human ARHGAP24 gene. Two isoforms of KIAA0053 type (D29642.1) and BM927439
      type were derived from human ARHGAP25 gene due to alternative splicing
      (alternative promoter). Mouse 0610025G21 (NM_029270.1) and A130039I20
      (AK037710.1) were representative cDNAs derived from mouse Arhgap24 and Arhgap25
      genes, respectively. Exon-intron structure of ARHGAP25 gene at human chromosome
      2p13 was slightly divergent from that of ARHGAP22 and ARHGAP24 genes. MGC35285,
      MAPK8 and C10orf64 genes linked to ARHGAP22 gene were paralogs of PTPN13, MAPK10
      and WDFY3 genes linked to ARHGAP24 gene, respectively. MGC35285-ARHGAP22-MAPK8
      C10orf64 locus at human chromosome 10q11 and the WDFY3-ARHGAP24-MAPK10-PTPN13
      locus at human chromosome 4q21 were paralogous regions (paralogons) within the
      human genome. Human ARHGAP24 showed 91.8% and 48.6% total-amino-acid identity
      with mouse Arhgap24 and human ARHGAP22, respectively. Human ARHGAP25 showed 86.1%
      and 40.8% total-amino-acid identity with mouse Arhgap25 and human ARHGAP22,
      respectively. ARHGAP22, ARHGAP24 and ARHGAP25 were found to constitute the RhoGAP
      subfamily featured by Pleckstrin homology (PH) domain and C-terminal Coiled-coil
      domain. This is the first report on identification and characterization of the
      ARHGAP24 and ARHGAP25 genes.

PMID- 15254789
TI  - Modulation of motor cortex excitability induced by pinch grip repetition.
AB  - We examined the influence of right handed pinch grips and the effect of a motor
      training on motor cortex excitability of the left first dorsal interosseus muscle
      (FDI). TMS single and paired pulses were applied over the right human motor
      cortex (M1) during and after right handed pinch grips with low force. In another
      experiment, these stimulations were performed before and after a 30-minute right
      handed pinch grip training. RESULTS: MEP amplitudes in left FDI were reduced when
      TMS single pulses were applied during the pinch grip. Simultaneously, motor
      cortex excitability was enhanced but returned to baseline after the training
      period. CONCLUSION: Phasic pinch grips of the right hand exert an inhibiting
      effect on the corticospinal excitability of the ipsilateral motor cortex and lead
      to an increase of intracortical excitability. These changes are distinct and
      independent of each other. Motor training has an interhemispheric effect on
      intracortical excitability.

PMID- 15254790
TI  - Modifications of apoptosis-related protein levels in lymphocytes of patients with
      Parkinson's disease. The effect of dopaminergic treatment.
AB  - In this study, we investigated whether changes in the regulatory mechanisms of
      apoptosis and oxidative stress may be detected, peripherally, in patients with
      Parkinson's disease (PD). For this purpose, we measured caspase-3 activity, Bcl-2
      concentrations, peripheral benzodiazepine receptor (PBR) expression and Cu/Zn
      superoxide dismutase (SOD) concentrations in lymphocytes of untreated PD
      patients, patients treated only with L-Dopa or with L-Dopa and dopamine agonists
      and healthy volunteers. Caspase-3 activity was significantly increased in all PD
      patient groups. Patients treated with L-Dopa and dopamine agonists showed the
      lowest values of Bcl-2, coupled with the highest density of PBRs, while increased
      levels of Cu/Zn SOD were found in the group under monotherapy with L-Dopa. We
      also found, in PD patients, clear, negative correlations between Bcl-2 levels and
      both duration and severity of the disease. Our findings point to the existence of
      changes in the regulatory mechanisms of apoptosis in PD patients -- observable
      outside the central nervous system -- which seem to be modulated by the
      pharmacological treatment with dopaminergic agents.

PMID- 15254791
TI  - Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of
      patients with Parkinson's disease.
AB  - Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine,
      serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinson's
      disease (PD) and 13 age-matched controls to ascertain the potential role of
      biological fluids as markers for this pathology. Analyses were performed by
      Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field
      Inductively Coupled Plasma Mass Spectrometry. The serum oxidant status (SOS) and
      anti-oxidant capacity (SAC) were also determined. Results showed a decreasing
      trend for Al in all the fluids of PD patients, with the strongest evidence in
      serum. Calcium levels in urine, serum and blood of PD patients were significantly
      higher than in controls. Copper and Mg concentrations were significantly lower in
      serum of PD patients. Levels of Fe in urine, blood and CSF of patients and
      controls were dissimilar, with an increase in the first two matrices and a
      decrease in CSF. No significant difference was found in levels of Mn between
      patients and controls. Urinary excretion of Si was significantly higher in PD
      subjects than in controls. No clear difference between Zn levels in the two
      groups was found for serum, urine or CSF, but an increase in Zn levels in the
      blood of PD patients was observed. The SOS level in PD was significantly higher
      while the corresponding SAC was found to be lower in patients than in controls,
      in line with the hypothesis that oxidative damage is a key factor in the
      pathogenesis of PD. The results on the whole indicate the involvement of Fe and
      Zn (increased concentration in blood) as well as of Cu (decreased serum level) in
      PD. The augmented levels of Ca and Mg in the fluids and of Si in urine of
      patients may suggest an involuntary intake of these elements during therapy.

PMID- 15254792
TI  - Comparison of alpha-dihydroergocryptine and levodopa monotherapy in Parkinson's
      disease: assessment of changes in DAT binding with [123I]IPT SPECT.
AB  - Putative neurotoxic actions of levodopa and neuroprotective effects of dopamine
      agonists, as indicated by laboratory and animal studies, provide the rationale to
      study their effect on the progression of Parkinson's disease. Aim of this pilot
      study was to compare the effects of monotherapy with the dopamine agonist alpha
      dihydroergocryptine (DEC) versus monotherapy with levodopa on nigrostriatal
      dopaminergic neurons as measured with dopamine transporter (DAT) SPECT. 25 PD
      patients (H&Y stages 1 to 2.5) entered this study and were treated in a
      randomized fashion either with DEC (101+/-39 mg) or levodopa (369+/-51 mg)
      monotherapy. 16/25 patients (8 per group) terminated the study after 52 weeks. In
      each patient SPECT investigations with [123I]IPT were performed at baseline and
      after 52 weeks to assess changes of specific DAT binding over time. Changes in
      clinical symptoms were assessed by UPDRS score. The mean annual decline rate in
      striatal IPT-binding was lower in the DEC group (8.4%) compared to the levodopa
      group (10.4%). The difference was most accentuated in the putamen (DEC: 7.3%;
      levodopa: 16.2%; p = 0.16). Due to the small sample size and the relatively short
      observation period, however, group differences did not reach a statistical
      significant level. The results of this pilot study suggest that as compared to
      levodopa monotherapy DEC may have beneficial effects on decline of dopamine
      transporter binding similar to those recently described for pramipexole.

PMID- 15254793
TI  - Combining entacapone with levodopa/DDCI improves clinical status and quality of
      life in Parkinson's Disease (PD) patients experiencing wearing-off, regardless of
      the dosing frequency: results of a large multicentre open-label study.
AB  - The efficacy of entacapone and its impact on patient quality of life (QOL) was
      investigated in an open-label study of 899 patients with idiopathic Parkinson's
      Disease (PD) experiencing wearing-off fluctuations. Patients were divided into 3
      groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency.
      Patients received 200 mg entacapone with each levodopa/dopa-decarboxylase
      inhibitor (DDCI) dose, while continuing their same levodopa/DDCI dosage regimen
      for 4 weeks. Primary efficacy measure was the Investigators' Clinical Global
      Impression of Change (CGIC). Patient QoL was assessed using the validated 8-item
      Parkinson's Disease Questionnaire (PDQ-8). Investigators' CGIC revealed that
      76.5% of entacapone treated patients experienced an improvement in global status
      after 4 weeks. Treatment with entacapone was also associated with improvement in
      patient QoL, with a mean reduction (improvement) in PDQ-8 score of 1.8 from
      baseline. This study confirms and extends the results of earlier studies
      demonstrating that, independent of dosing frequency, completing levodopa/DDCI
      therapy with entacapone provides clinically relevant improvements in global
      status and QoL in PD patients experiencing wearing-off on their current levodopa
      dosing frequency.

PMID- 15254794
TI  - Presynaptic nigro-striatal function in a group of Alzheimer's disease patients
      with parkinsonism: evidence from a dopamine transporter imaging study.
AB  - The occurrence of parkinsonism in Alzheimer's disease (AD) is quite common,
      however the molecular and neurochemical changes underlying such extrapyramidal
      features in AD have been not fully understood. Post-mortem as well as in vivo
      imaging study have produced conflicting results as regards the existence of
      dopaminergic changes in AD. Aim of the present study was to investigate in vivo
      the nigro-striatal dopaminergic function in a group of AD patients with
      parkinsonism. Thirteen patients with AD and extrapyramidal features not related
      to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of
      dopamine transporter, and the data were compared with those obtained in 15
      patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson's
      disease (PD), and 8 healthy elderly controls. The analysis of the data was
      performed by regions-of-interest approach and calculations of the striatal-to-non
      specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT
      striatal uptake in patients with AD-P was similar to that obtained in the control
      population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT
      uptake in all striatal areas with respect to AD-P and control groups (p < 0.005).
      The lack of dopamine transporter changes in our series of AD-P patients can
      indicate that dopaminergic presynaptic function is preserved in this population
      and that different dopaminergic changes such as postsynaptic ones, or different
      neurotransmitter alterations might underlie the extrapyramidal features in AD.

PMID- 15254795
TI  - Effects of haloperidol on cholinergic striatal interneurons: relationship to oral
      dyskinesias.
AB  - In a subset of rats, typical antipsychotic drugs (tAPD) produce oral dyskinesias
      called vacuous chewing movements (VCMs) that resemble tardive dyskinesia (TD), a
      behavioral side effect seen in a subset of people following tAPD treatment.
      Morphological changes within the striatum following tAPD have been correlated to
      VCMs in animal models. The cholinergic system has been implicated in expression
      of TD. To test the hypothesis that the striatal cholinergic system is perturbed
      after haloperidol treatment, rats were administered haloperidol for three weeks
      and tested for VCMs; the striata were then processed for the immunocytochemical
      localization of choline-acetyltransferase (ChAT). Neuronal density measures of
      ChAT-labeled neurons showed a 22% decrease in haloperidol-treated versus controls
      rats and a 37% reduction in the lateral portion of the striatum only in rats with
      VCMs. These findings further support evidence of the possible involvement of the
      cholinergic system and the ventrolateral striatum in VCMs, and possibly TD.

PMID- 15254796
TI  - GSK-3beta in cerebrospinal fluid of schizophrenia patients.
AB  - Cerebrospinal fluid contains proteins and metabolites of brain origin and was
      extensively studied in psychiatry in the 1970's with few definitive results. We
      have recently found 40% reduced protein levels of GSK-3beta in schizophrenia in
      postmortem prefrontal cortex, but our attempt to develop a diagnostic marker
      using peripheral lymphocyte GSK-3beta was not successful. In this study we aimed
      to find whether the reduction in brain GSK-3beta is reflected in CSF of
      schizophrenia patients. We report a significant reduction in CSF GSK-3beta
      protein levels in six schizophrenia patients compared to seventeen healthy
      subjects. Our results corroborate other studies in which CSF protein levels
      reflect the alteration found in these proteins in schizophrenia patients'
      postmortem brain.

PMID- 15254797
TI  - Results of surgical and endovascular treatment of intracranial micro
      arteriovenous malformations with emphasis on superselective angiography.
AB  - BACKGROUND: The authors retrospectively reviewed the results of two different
      treatment modalities (surgery and endovascular approach) in patients with
      intracranial micro-arteriovenous malformations (micro-AVMs). The goal of this
      study is to evaluate the respective role of surgical treatment and superselective
      acrylic embolization in the management of micro-AVMs. METHOD: Fourteen patients
      with micro-AVMs who had been treated by surgical resection or endovascular
      acrylic embolization during a 6-year period were analyzed. The average age at
      presentation was 44.6 years (range, 24-65 yr) with no sex dominance. All patients
      presented with an intracranial haemorrhage, which was superficial in twelve
      patients and in eloquent brain areas in seven patients. Severe neurological
      deficits were observed in eleven patients. FINDINGS: Digital subtraction
      angiography (DSA) demonstrated micro-AVMs in eleven patients (78.5%) while in
      three patients (21.5%) the micro-AVM was detected only by superselective
      angiography (SA). Eight patients underwent surgical intervention which led to
      definitive resection in seven with no peri-operative morbidity. SA was performed
      in nine patients and followed by successful acrylic embolization of the micro-AVM
      in seven with haemorrhagic complications in two patients. All fourteen lesions
      were completely obliterated as demonstrated angiographically. Outcomes were
      classified according to the Modified Rankin Scale. With a mean long term clinical
      follow-up of 33 months (range, 8-75 mo), seven patients were Grade 0, six
      patients were Grade I and one patient was Grade IV. CONCLUSIONS: SA is deemed
      necessary to visualize micro-AVMs in case of questionable or negative findings
      also at delayed DSA in young healthy patients with otherwise unexplained
      intracranial haemorrhage. Obliteration of micro-AVM can be accomplished either
      surgically or endovascularly; however, the endovascular approach is associated
      with a defined procedural risk for haemorrhagic complications and long term
      angiographic follow-up is necessary.

PMID- 15254798
TI  - The role of surgery in the treatment of brain metastasis: a retrospective review.
AB  - BACKGROUND: To study the role of surgery for brain metastasis, we reviewed the
      records of 646 patients with brain metastasis. METHODS: 340 patients underwent
      operative removal of the brain metastasis. During the same period, another 306
      patients were treated without surgery. Criteria for surgery included the
      anatomical site, size over 3 cm, and cystic changes. Outcome was assessed by
      survival and cause of death. TREATMENT: 340 patients received surgical treatment,
      and 210 of these received radiation therapy. Another 306 patients were treated
      without surgery; 250 patients received conventional radiation and 56 patients
      were treated radiosurgically using a gamma knife. The surgical group was younger
      and had a better Karnofsky score than those of the non-surgical group. The median
      survival periods in the surgical and non-surgical groups were 21.0 months and 8.0
      months, respectively. In patients whose brain lesions were first found before the
      systemic disease, the 5 year survival rates for the surgical and non-surgical
      groups were 35.2% and 18.2%, respectively. Although neurological causes accounted
      for 33.0% of deaths in the non-surgical group, and 13.2% of deaths in the
      surgical group; this difference was not significant. CONCLUSIONS: This
      retrospective review showed that patients with a brain metastasis treated
      surgically survived longer with better tumor control. To determine if this
      summary reflects the critical prognostic imbalance of population, further studies
      with randomized comparison are required.

PMID- 15254799
TI  - Limitations of dorsal transpedicular stabilization in unstable fractures of the
      lower thoracic and lumbar spine: an analysis of 133 patients.
AB  - The optimal treatment of thoracic and lumbar fractures remains controversial.
      While many authors recommend dorsal instrumentation with an internal fixator,
      others favour an anterior approach. To evaluate the posterior approach and to
      identify conditions under which an anterior approach should be preferred, 133
      patients with unstable thoracic and lumbar fractures of the spine who underwent
      dorsal instrumentation with an internal fixator were analyzed. Clinical data were
      recorded prospectively with respect to fracture type, neurological findings,
      operative complications, spinal deformation correction, and long-term outcome.
      All fractures were located between the 7th thoracic and the 5th lumbar vertebrae
      and were considered to be unstable with respect to the three column model.
      Seventy-six patients (57%) received surgery within the first seven days after the
      trauma. Postoperatively, 98% of patients with a radicular lesion or an incomplete
      transverse syndrome (47 patients, 35%) improved. Stable fracture consolidation
      after fixator removal was obtained in 98% (130 of 133 patients). The preoperative
      kyphosis angle decreased from an average of 10.1 degrees to 7.4 degrees at the
      three year follow up. Major operative complications consisted of two isolated
      nerve root lesions (1.5%), two deep wound infections with need of fixator removal
      (1.5%), and mallocation of two pedicle screws with need for another procedure in
      two patients (1.5%). Three patients (2%) suffered from insufficient bony fusion
      with increase of kyphotic deformation and required subsequent anterior
      stabilization. These three patients presented with an initial kyphosis or wedge
      angle of 20 degrees or higher. In conclusion, dorsal stabilization with the
      internal fixator is a safe and reliable treatment for unstable fractures of the
      lower thoracic and lumbar spine. The authors recommend this procedure because of
      its low-invasiveness in conjunction with satisfactory reconstruction and
      stabilization. However, an anterior approach should be considered in fractures
      with initial kyphotic deformation or wedge angle of 20 or more degrees.

PMID- 15254800
TI  - Occipital condyle fractures: a hidden nosologic entity. An experience with 10
      cases.
AB  - INTRODUCTION: To report the incidence, treatment and outcome of occipital condyle
      fractures (OCFs) based on the experience of a single neurosurgical department
      over a period of two years. MATERIAL AND METHODS: From April 1999 to April 2001,
      ten cases of OCFs were identified in 110 cervical traumas observed over a period
      of two years. Patients were studied by cervical x-rays, high-resolution CT scan
      with a 1-2 mm slice of the cranio-cervical junction (CCJ) and MRI in selected
      cases to evaluate the integrity of supporting ligaments. According to the
      Anderson and Montesano classification, 5 cases of type III, 3 cases of type II
      and 2 cases of type I fractures were found. Dysfunction of lower cranial nerves
      was observed in 8 cases. Treatment was conservative in all cases. RESULTS: At
      follow-up, ranging from 18 months to 2 years, fusion was obtained in all cases; 8
      patients were neurologically intact, one patient presented a mild persistent
      dysphonia and another mild trapezius weakness. CONCLUSION: OCFs are actually not
      rare, rather they are often overlooked. In cases of high-energy trauma of the
      cervical spine, the diagnostic suspicion should be kept in mind.High-resolution
      CT scan with slice at 1-2 mm of the CCJ is the key radiological examination in
      the diagnosis of this lesion. Conservative treatment using a hard collar is
      sufficient to obtain sound fusion.

PMID- 15254801
TI  - Intraventricular craniopharyngiomas: topographical classification and surgical
      approach selection based on an extensive overview.
AB  - BACKGROUND: This retrospective study analyzes the clinical, neuroradiological,
      pathological and surgical characteristics of well-described intraventricular
      craniopharyngiomas with the aims of: (i) critically to review the criteria used
      to affirm the diagnosis of an intraventricular location (ii) defining more
      accurately this topographical diagnosis preoperatively, and (iii) to investigate
      factors influencing the surgical outcome. METHOD: Clinical, neuroradiological,
      pathological and surgical objective data of 104 well-described intraventricular
      craniopharyngiomas (IVC) reported in the literature, in addition to a new case,
      were analyzed. On the basis of the proofs provided for third ventricle
      intactness, a new topographical classification for IVC was developed,
      distinguishing between: (i) strict IVC, with a proved third ventricle floor
      integrity and (ii) non-strict IVC, without any reliable proof confirming the
      intactness of the third ventricle floor. Following this classification, clinical
      features, pathology and surgical outcome for strictly and non-strictly IVC were
      compared. FINDINGS: For 105 IVC compiled, 36 belonged to the strictly group and
      69 to the non-strictly group. Two pathological features were associated with the
      non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and
      wider and tighter adherences to third ventricle margins (p=0.01). The non-strict
      topography was also associated with a worse postoperative outcome (p=0.046).
      There was a significant relationship between the surgical approach and the final
      outcome (p=0.05), being the translamina terminalis approach associated with the
      best outcome. CONCLUSIONS: Two different topographies might be considered among
      IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider
      and tighter adhesions to third ventricle boundaries and this subtype is
      associated with a worse outcome.

PMID- 15254802
TI  - Laser-induced thermotherapy of neoplastic lesions in the brain--underlying tissue
      alterations, MRI-monitoring and clinical applicability.
AB  - Laser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach
      to the stereotactic treatment of brain tumors in poorly accessible regions. Its
      clinical applicability has been shown in several experimental and clinical
      studies under on-line monitoring by magnetic resonance imaging (MRI). This review
      characterizes LITT as an alternative neurosurgical approach with specific focus
      on the typical histological alterations and ultrastructural cellular changes
      following laser irradiation in the central nervous system. The spatial and
      temporal pattern of these changes is discussed in their relevance to the
      neurosurgical treatment of neoplastic lesions using LITT.

PMID- 15254803
TI  - Biomechanical analysis of cervical multilevel oblique corpectomy: an in vitro
      study in sheep.
AB  - BACKGROUND: Anterolateral oblique corpectomy is an alternative approach to
      treatment of multilevel cervical spinal disease. It is stated that the approach
      does not cause instability in the patients with hard discs, so fusion or
      instrumentation is not required. The authors undertook a study on stability of
      the cervical spine by an animal model to establish if this approach causes
      instability. MATERIAL AND METHODS: Thirty-seven C3 to C6 spinal segments obtained
      from 3 to 4-year-old male sheep were used. In vitro maximal loading values were
      obtained from seven sheep cervical specimens for flexion, extension, lateral
      flexion in both directions, axial rotation in both directions and axial loading,
      and load deformation curves were drawn by an electrohydrolic testing machine.
      Other specimens were divided into three groups: Control (n=10), C4 (n=10) and C4
      5 (n=10) groups. In two study groups, one or two level oblique corpectomies were
      performed. In the control and study groups, biomechanical tests were obtained
      according to the maximal loading values. Load-deformation curves were drawn and
      displacement amounts were determined for all seven movements. RESULTS: No
      statistically significant differences were observed in load deformation curves
      and displacement amounts between all three groups for seven movements.
      CONCLUSION: These results support the opinion that anterolateral oblique
      corpectomy does not cause cervical instability.

PMID- 15254804
TI  - Differential effects of prolonged isoflurane anesthesia on plasma, extracellular,
      and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain
      edema in traumatic brain-injured rats.
AB  - BACKGROUND: Volatile anesthetics reduce neuronal excitation and cerebral
      metabolism but can also increase intracellular water accumulation in normal and
      injured brains. While attenuation of neuronal excitation and glutamate release
      are beneficial under pathological conditions, any increase in edema formation
      should be avoided. In the present study we investigated duration-dependent
      effects of the commonly used isoflurane/nitrous oxide (N2O) anesthesia on EEG
      activity, specific NMDA receptor binding, extracellular, CSF, and plasma
      glutamate, and cerebral water content in brain-injured rats subjected to short
      (30 minutes) or prolonged (4 hours) anesthesia. METHODS: Before controlled
      cortical impact injury (CCI), during prolonged (4-8 hours) or short anesthesia
      (7.5-8 hours after CCI), and before brain removal, changes in neuronal activity
      were determined by quantitative EEG analysis and glutamate was measured in
      arterial plasma. Brains were processed to determine acute and persisting changes
      in cerebral water content and 125I-Mk801 NMDA receptor binding at 8 and 32 hours
      after CCI, i.e., immediately or 24 hours after short or prolonged anesthesia.
      During prolonged anesthesia glutamate was measured via microdialysis within the
      cortical contusion. CSF was sampled before brain removal. FINDINGS: Prolonged
      isoflurane (1.8 vol%) anesthesia significantly increased EEG activity, plasma,
      cortical extracellular, and CSF glutamate, cortical and hippocampal 125I-Mk801
      NMDA receptor binding, and cerebral water content in brain-injured rats. These
      changes were partially reversible within 24 hours after prolonged anesthesia. At
      24 hours, CSF glutamate was significantly reduced following long isoflurane
      anesthesia compared to rats previously subjected to short anesthesia despite an
      earlier significant increase. Conclusions. The partially reversible increases in
      EEG activity, 125I-Mk801 NMDA receptor binding, cerebral water content, plasma
      and CSF glutamate appear important for physiological, pathophysiological, and
      pharmacological studies requiring prolonged anesthesia with isoflurane. Increases
      in extracellular cortical and plasma glutamate could contribute to acute
      aggravation of underlying tissue damage.

PMID- 15254805
TI  - Expression of cell proliferation markers in pituitary adenomas--correlation and
      clinical relevance of MIB-1 and anti-topoisomerase-IIalpha.
AB  - Pituitary adenomas represent an inhomogeneous tumor entity in terms of growth
      rate, invasiveness and recurrence. To improve understanding of their different
      biological behaviour, tumor cell proliferation markers are applied. The aim of
      this study was to assess proliferation rates overall and in clinico-pathological
      subgroups using MIB-1 and the recently introduced cell proliferation marker anti
      topoisomerase-IIalpha (Topo-IIalpha). Further, we correlated the two markers, and
      defined the clinical value of Topo-IIalpha in pituitary adenomas as compared to
      MIB-1. We analyzed tumor cell proliferation rates using MIB-1 and Topo-IIalpha
      antibodies on samples of 260 primary pituitary adenomas. We excluded recurrent
      cases and cases with drug pretreatment. Median patient age at the time of surgery
      was 47 years (range 14-86 years), the male:female ratio was 1:1. The total cohort
      comprised 110 non-functioning and 150 functioning cases. Subtyping was performed
      according to hormonal expression as defined by WHO. Tumor size and invasiveness
      were noted from surgical and/or radio logical reports in 95% of cases. Overall
      MIB-1 index was median 1.8% (range 0.2-23.6%), Topo-IIalpha index was median 1.0%
      (range 0-14.4%) with a strong correlation between the two markers ( R=0.837,
      P<0.001). As compared to MIB-1, mean Topo-IIalpha values were significantly lower
      by a factor 1.8. Only MIB-1 was significantly higher in invasive as compared to
      non-invasive adenomas, in tumors < or =3 cm in diameter, and in the age-group 21
      40. Female gender had significantly higher MIB-1 and Topo-IIalpha indices than
      male. Silent ACTH-cell and PRL-producing adenomas had the highest, null-cell
      adenomas and gonadotropinomas the lowest proliferation values, respectively. Our
      data show a strong correlation between MIB-1 and Topo-IIalpha indices in
      pituitary adenomas. Only MIB-1 but not Topo-IIalpha demonstrated significantly
      higher values in invasive adenomas. Therefore, MIB-1 seems more useful than Topo
      IIalpha for decisions regarding postoperative patient management.

PMID- 15254806
TI  - Vanishing contrast enhancement in malignant glioma after corticosteroid
      treatment.
AB  - Malignant gliomas of the brain typically exhibit on CT or MRI a strong peripheral
      contrast enhancement area with a variable central zone of necrosis. These tumours
      are not known to change their radiological appearance and contrast enhancement
      pattern under systemic steroid treatment--a feature usually associated with
      primary CNS lymphoma. We report two cases of adult patients with glioblastoma
      multiforme and atypical hemispherical contrast enhancement initially demonstrated
      on MRI or CT, which disappeared after dexamethasone administration. At the same
      time, however, another tumour focus became visible, in both cases localised in
      the corpus callosum. Histological diagnosis was confirmed by stereotactic biopsy
      in both cases. This unusual changing pattern of contrast enhancement seems to be
      associated with multifocal malignant glioma with partial blood-brain barrier
      disruption modified by dexamethasone, and may present diagnostic difficulties in
      respect to neuroimaging and selection of target areas for tumour biopsy.

PMID- 15254807
TI  - A case of delayed brain abscess due to a retained intracranial wooden foreign
      body: a case report and review of the last 20 years.
AB  - A 13-year-old female is presented. When she was six years old, she had fallen,
      holding wooden chopsticks and got stuck with a chopstick in the right upper
      eyelid. She was brought to a physician immediately, but a residual foreign body
      was missed and no particular symptom had developed during 7 years. She visited
      our department with fever and headache, and a brain abscess and an intracranial
      foreign body were found on computed tomography (CT) and magnetic resonance image
      (MRI) 7 years after the penetrating injury. She underwent removal of the object
      and abscess by craniotomy and recovered without neurological abnormalities. Since
      intracranial retained wooden foreign bodies frequently cause delayed
      complications of severe central nervous system infection, surgical removal is
      necessary even in the absence of symptoms.

PMID- 15254808
TI  - CNS aspergillosis with mycotic aneurysm, cerebral granuloma and infarction.
AB  - We are reporting a case of an immunocompromised patient with invasive
      aspergillosis (IA) who developed aspergillotic granulomas and a mycotic aneurysm
      of the superior cerebellar artery. The route of infection of the central nervous
      system (CNS) was hematogenous spread from a pulmonary focus. IA was detected with
      the Galactomannan (GM) technique. However, despite treatment with amphotericin B,
      progressive involvement of the vessel wall occurred causing fatal subarachnoid
      hemorrhage and massive brainstem and cerebellar infarction. This case provides
      pathologic-imaging correlation of one of the most devastating types of fungal
      involvement affecting the CNS with a fungal aneurysm. Finally the literature
      regarding the pathogenetic, and diagnostic investigations and the management of
      CNS aspergillosis is reviewed.

PMID- 15254809
TI  - Intradural spinal metastasis of renal clear cell carcinoma causing cauda equina
      syndrome.
AB  - Metastasis of renal clear cell carcinoma to the spinal cord are quite rare.
      Intradural localization causing a cauda equina syndrome has been previously
      reported only in two cases. The present report details the clinical, surgical and
      neuroradiological findings of a third case requiring emergency surgery, and
      presents data available from a brief review of cases reported in the literature.
      From the data available in the literature, we suggest that cerebral and spinal
      MRI and PET imaging should be widely performed in the staging of patients treated
      for renal clear cell carcinoma, in order to early detect CNS involvement.

PMID- 15254810
TI  - Solitary skull vault plasmacytoma masquerading as an extradural haematoma.

PMID- 15254814
TI  - [In our own case: listing in Index Medicus and new rubric].

PMID- 15254815
TI  - [Zoonotic infections stimulation].

PMID- 15254816
TI  - [The emergence of old and new epidemics as a consequence of human actions].
AB  - In the era of antibiotics and vaccines and prior to the appearance of AIDS, well
      known infectious diseases received decreasing clinical attention. Occasionally,
      the opinion was also expressed that new types of infectious diseases could no
      longer be expected. However, a more detailed analysis of the state of infectious
      diseases yields quite a different picture. A variety of new infectious diseases
      has clinically been defined over the last few decades. New viruses, bacteria, and
      parasites with pathogenic potential for humans have been detected and well-known
      microorganisms have spread beyond their original geographic areas. Infectious
      agents, in particular viruses, permanently alter their genomes and may thus gain
      new clinical relevance. This article demonstrates that primarily the behavior of
      man influenced the nature and distribution of infectious diseases in the past and
      will affect the spread of infectious diseases in the future.

PMID- 15254817
TI  - [Zoonotic infections in humans. Review of the epidemiological situation in
      Germany].
AB  - Zoonoses are infectious diseases that can be transmitted from vertebrate animals
      to humans. Their significance lies in the large number of cases that occur, the
      high case fatality ratio of certain zoonoses, and the potential for some
      pathogens as yet restricted to animal hosts to cross the species barrier and
      infect humans. Changing habits in food production (for example, intensive animal
      husbandry) and food consumption as well as demographic, climatic, and ecological
      factors contribute to the spread of zoonotic pathogens. Several zoonoses are
      notifiable in Germany according to the Protection Against Infection Act enacted 1
      January 2001. The European Commission issued a new directive on the monitoring of
      zoonoses and zoonotic agents on 17 November 2003. There is ongoing need to
      develop further measures to prevent and control zoonotic diseases on a national
      as well as international basis.

PMID- 15254818
TI  - [Zoonoses in working- and wild animals and their significance in Germany. An
      overview].
AB  - The control of infectious diseases transmitted from animals to humans (zoonoses)
      was recently put on a new basis in the European Union when a new Zoonoses
      Directive entered into force. Brucellosis, campylobacteriosis, echinococcosis,
      listeriosis, salmonellosis, trichinosis, and the respective causative agents,
      tuberculosis due to Mycobacterium bovis, and verotoxigenic Escherichia coli must
      be included in monitoring. Additional zoonoses and zoonotic agents are to be
      monitored according to the epidemiological situation. Against this background,
      the current knowledge on important zoonoses transmitted from livestock and some
      wildlife animals to humans as well as the epidemiological situation in Germany
      with regard to these diseases is summarized.

PMID- 15254819
TI  - [Relevance of coronaviruses. The SARS example].
AB  - The emergence of the new SARS coronavirus has shown dramatically the high
      relevance of human coronavirus infections. This overview presents data of both
      epidemiological and clinical studies of this new virus infection. Moreover,
      details of research on the pathogenesis, diagnostics, and therapy are given. The
      recent infections in December 2003 clearly document that SARS will be a major
      topic also in 2004.

PMID- 15254820
TI  - [West Nile virus. Prevalence and significance as a zoonotic pathogen].
AB  - The spread of West Nile virus (WNV) in North America since 1999 has reawakened
      concern about this pathogen in Europe. WNV can cause West Nile fever in humans,
      and in a small proportion (around 1 in 150) the disease can take a severe course
      associated with symptoms of the central nervous system (encephalitis) and even
      death, particularly in older patients (>70 years). In contrast to the USA, where
      the virus has spread from New York thronghout the continent to the west coast,
      only temporally and regionally limited outbreaks of WNV infections have been
      observed in Europe since the 1950s. Birds serve as the reservoir for WNV and the
      transmission of the virus occurs predominantly via mosquitoes. Ornithophilic
      mosquitoes transmit the virus amongst the bird population while those mosquito
      species that feed on both birds and mammals can transmit the pathogen also to
      humans. However, mammals are considered to be blind alleys that do not contribute
      to the epidemic spread of the pathogen. The differences so far observed between
      the epidemics in North America and in Europe might be explained by the following
      considerations: Europe has long had contact with WNV-endemic areas in Africa via
      migratory birds, whereas the pathogen was first imported into the USA in 1999
      where it has infected a "naive" bird population. It is possible that the strain
      presently spreading through the USA is highly pathogenic, whereas strains of
      varying pathogenic potential circulate in Africa. This could resulut in a natural
      immunization of the bird population through contact to strains of low
      pathogenicity. The possibility of a natural resistance in European birds is also
      being considered since these animals have been confronted with the pathogen for
      long periods of time. Investigations into the prevalence and incidence of WNV
      infections in German bird populations as well as in dead end hosts such as humans
      and horses should provide information regarding the potential risk represented by
      WNV.

PMID- 15254821
TI  - [Prevalence of hantavirus infections in Germany].
AB  - Hantaviruses belong to the group of "emerging" viruses. Pathogenic European
      hantaviruses can cause a human disease designated "hemorrhagic fever with renal
      syndrome" of varying severity. In general, diagnostics of hantavirus infections
      are based on immunofluorescence assays using virus-infected cells or enzyme
      immunoassays and Western blot tests using recombinant nucleocapsid proteins. For
      highly sensitive detection of hantavirus-specific antibodies in the enzyme
      immunoassay, a homologous hantavirus nucleocapsid protein is needed as a
      diagnostic antigen. Serological typing of hantavirus infections can be obtained
      by neutralization assays, which in certain cases require the use of late
      convalescent sera. The seroprevalence in the normal German population is about
      1%. In professionally exposed risk groups, e. g., forest workers, a
      seroprevalence higher than that in the normal population was observed. Endemic
      regions for hantavirus infections are located mainly in Baden-Wurttemberg. In the
      years 2001-2003 an annual number of about 200 clinically apparent hantavirus
      infections were registered in Germany. Neutralization assays detected almost
      exclusively human infections caused by Puumala and Dobrava viruses, only very
      rarely by Tula virus. Until this day in Germany mainly mild to moderate courses
      of human hantavirus infections have been documented. Besides infections caused by
      "German" hantaviruses, up to 10% of the clinically apparent hantavirus infections
      registered annually in Germany are caused by infections imported from other
      countries, mainly from Europe. So far only very limited molecular genetic data
      about the circulating hantaviruses in Germany are available. Additional
      investigations are needed to get a more precise picture about the distribution of
      hantaviruses in Germany and to calculate the resulting risk for the human
      population.

PMID- 15254822
TI  - [Zoonotic poxviruses].
AB  - In the last few years, the mass media and also scientists have been showing an
      increasing interest in poxviruses. What kind of infections can be found in
      animals and men today? The following review gives an overview on current
      taxonomy, properties, epidemiology, and diagnosis of zoonotic poxviruses.

PMID- 15254823
TI  - [SIV as a source of HIV. On the origin of human immunodeficiency viruses from non
      human primates].
AB  - It is assumed that HIV, the human immunodeficiency virus, started its spread
      after the Second World War. Molecular analysis of the genome of various HIV-1
      types has shown that this virus can be divided into the groups M, N, and O and
      that these genome sequences fit perfectly to the genomes found in SIV of
      chimpanzees (SIVcpz) living in the area of West and Central Africa. SIVcpz is
      nonpathogenic for chimpanzees indicating that the virus and host have adapted for
      a long period. HIV-2 genome sequences converge with SIV sequences of sooty
      mangabey monkeys from West Africa (SIVsm), covering the subtypes A to G from HIV
      2. SIVsm is nonpathogenic for mangabey monkeys. All available data indicate that
      HIV-1 and HIV-2 have been introduced into humans at least several times. Since
      SIVcpz and SIVs from other monkeys are recombinant viruses, it cannot be excluded
      that a new recombinant SIV might again enter the human population and initiate a
      new epidemic.

PMID- 15254824
TI  - [Intestinal yersiniosis. Clinical importance, epidemiology, diagnosis, and
      prevention].
AB  - Yersinia enterocolitica and Y. pseudotuberculosis are causative agents of
      yersiniosis in humans and animals that have to be separated from Y. pestis, the
      causative agent of plague, representing a separate clinical and epidemiological
      entity. Intestinal yersiniosis may manifest in humans as (1) enteritis, (2)
      terminal ileitis, mesenteric lymphadenitis, or pseudoappendicitis, and (3)
      septicemia leading to focal abscesses in spleen and liver. The intestinal
      infection may be followed by reactive arthritis in a number of cases. Y.
      enterocolitica and Y. pseudotuberculosis are distributed worldwide but occur
      mainly in moderate or subtropical climates. The most important reservoirs are
      rodents, lagomorphs, and birds for Y. pseudotuberculosis and domestic animals,
      especially pigs, for Y. enterocolitica. All Y. pseudotuberculosis isolates may be
      considered as pathogenic whereas Y. enterocolitica strains can be subdivided into
      pathotypes of different virulence. The differentiation of pathotypes by
      determination of the biovar and demonstration of the 75-kb virulence plasmid is
      therefore of diagnostic importance. Preventive measures include avoidance of
      direct infection by contact with infected reservoir animals and practice of good
      hygiene during slaughtering as well as in food production and preparation of
      meals.

PMID- 15254825
TI  - [Prevalence and public-health-aspects of toxoplasmosis].
AB  - Toxoplasmosis is one of the most common infectious diseases of man, which usually
      is not dangerous. Infection results from ingestion of cyst-containing meat
      products or by contact with oocyst-contaminated soil. Clinically relevant are (1)
      reactivation of latent infection in immunocompromised individuals or (2) primary
      infection during pregnancy with subsequent prenatal toxoplasmosis of the fetus.
      In Germany, law requires the prenatal infection to be reported to the Robert Koch
      Institute. Since most Toxoplasma-infected children are asymptomatic at birth and
      later develop sequelae (retinochoroiditis) up to the age of 20 years, no valid
      epidemiological data are currently available for Germany. However, some studies
      indicate that seroprevalence correlates with age and that 26-54% of women of
      childbearing age have antibodies against Toxoplasma gondii; incidence rates
      during pregnancy have been calculated to be between 0.5 and 0.6%. Knowing the
      life cycle of Toxoplasma gondii will help to maintain preventive measures for
      seronegative pregnant women, children, and immunocompromised individuals.

PMID- 15254826
TI  - [Parasitic zoonoses transmitted by drinking water. Giardiasis and
      cryptosporidiosis].
AB  - Nowadays, the parasitic zoonose organisms Giardia lamblia und Cryptosporidium
      spp. are among the most relevant pathogens of drinking water-associated disease
      outbreaks. These pathogens are transmitted via a fecal-oral route; in both cases
      the dose of infection is low. Apart from person-to-person or animal-to-person
      transmissions, the consumption of contaminated food and water are further modes
      of transmission. The disease is mainly characterized by gastrointestinal
      symptoms. In industrialized countries, the prevalence rate of giardiasis is 2-5 %
      and of cryptosporidiosis 1-3%. Throughout the world, a large number of giardiasis
      and cryptosporidiosis outbreaks associated with drinking water were published; in
      2001 the first case in Germany was identified. Giardia and Cryptosporidium are
      detected in surface water and sporadically in unprotected groundwater. Use of
      these waters for drinking water abstraction makes high demands on the technology
      of the treatment process: because of the disinfectant resistance of the
      parasites, safe elimination methods are needed, which even at high contamination
      levels of source water guarantee safe drinking water. Further measures for
      prevention and control are implementation of the HACCP concept, which includes
      the whole chain of procedures of drinking water supply from catchment via
      treatment to tap and a quality management system.

PMID- 15254827
TI  - [Reference values for indoor room air: naphthalene].

PMID- 15254830
TI  - Effects of continuous water flow on the swelling properties of polyelectrolyte
      hydrogels.
AB  - We report the swelling behavior of a polyelectrolyte copolymer gel in water,
      which consists of poly(N-isopropylacrylamide) and sodium acrylate. The diameter
      of the cylindrical gels was measured at room temperature under a continuous flow
      of solvent water (equivalent to an infinite amount of water; open system). After
      a sufficient water flow, the diameter of the gel in the limited amount of water
      (closed system) was measured as a function of the temperature. The gel in the
      open system was found to shrink as a result of the continuous flow of water, and
      the gel in the closed system began to swell again at the phase transition point
      by increasing the temperature. The effects of the degree of initial ion exchange
      by the water flow on the macroscopic swelling behavior were discussed in terms of
      the exchange of counterions (the ion dissociation of carboxyl groups) and of the
      creation and destruction of intermolecular forces (hydrogen bonding). It was
      concluded that the amount of solvent water determines the environmental
      variables, such as the pH and ion concentration, which affects the swelling
      properties of polyelectrolyte hydrogels; intermediate re-swollen states can be
      observed in a closed system.

PMID- 15254831
TI  - Random anisotropy nematic model: connection with experimental systems.
AB  - We study theoretically the phase behavior of the continuum Random Anisotropy
      Nematic model. A domain-type pattern is assumed to appear in a distorted nematic
      liquid crystal (LC) phase. We map the model parameters to physical quantities
      characterizing LCs confined to Controlled-Pore Glasses and LC-aerosil
      dispersions. The domain size dependence on the disorder strength is obtained in
      accordance with the Imry-Ma prediction. The model estimates for temperature
      shifts of the paranematic-nematic phase transition and for the critical point,
      where this transition ceases to exist, are compared to the available experimental
      results.

PMID- 15254832
TI  - Stationary shear flows of dense granular materials: a tentative continuum
      modelling.
AB  - We propose a simple continuum model to interpret the shearing motion of dense,
      dry and cohesion-less granular media. Compressibility, dilatancy and Coulomb-like
      friction are the three basic ingredients. The granular stress is split into a
      rate-dependent part representing the rebound-less impacts between grains and a
      rate-independent part associated with long-lived contacts. Because we consider
      stationary flows only, the grain compaction and the grain velocity are the two
      main variables. The predicted velocity and compaction profiles are in apparent
      qualitative agreement with most of the experimental or numerical results
      concerning free-surface shear flows as well as confined shear flows.

PMID- 15254834
TI  - Can experiments select the configurational component of excess entropy?
AB  - Configurational entropy is frequently used to rationalize the structural dynamics
      of glass-forming liquids. The main problem with this concept is that it is not
      directly accessible to experiments. We introduce a procedure to estimate the
      configurational component of the excess entropy of a liquid --specifically, the
      configurational-entropy contribution from the structural relaxation process--
      through a combined investigation of dynamic and thermodynamic properties as
      functions of temperature and pressure. We test our method on orthoterphenyl,
      salol, and glycerol, and find that the fraction of excess entropy that arises
      from structural configurations is about 70% for all three materials.

PMID- 15254833
TI  - Ionic diffusion and space charge polarization in structural characterization of
      biological tissues.
AB  - In this study, a new approach to the analysis of the low-frequency (1-10(7) Hz)
      dielectric spectra of biological tissue, has been described. The experimental
      results are interpreted in terms of ionic diffusion and space charge polarization
      according to Sawada's theory. The new presentation of dielectric spectra, i.e.
      ([Formula: see text]) [Formula: see text] has been used. This method results in
      peaks which are narrower and better resolved than both the measured loss peaks
      and an alternative loss quantity [Formula: see text]. The presented method and
      Sawada's expression have been applied to the analysis of changes in the spatial
      molecular structure of a collagen fibril network in pericardium tissue exposed to
      glutaraldehyde (GA), with respect to the native tissue. The diffusion coefficient
      of ions was estimated on the basis of a dielectric dispersion measurement for an
      aqueous NaCl solution with a well-calibrated distance between the electrodes. The
      fitting procedure of a theoretical function to the experimental data allowed us
      to determine three diffusive relaxation regions with three structural distance
      parameters d(s), describing the spatial arrangement of collagen fibrils in
      pericardium tissue. It has been found that a significant decrease in the
      structural distance d(s) from 87 nm to 45 nm may correspond to a reduction in the
      interfibrillar distance within GA cross-linked tissue.

PMID- 15254835
TI  - Measurement of membrane elasticity by micro-pipette aspiration.
AB  - The classical micro-pipette aspiration technique, applied for measuring the
      membrane bending elasticity, is in the present work reviewed and extended to span
      the range of pipette aspiration pressures going through the flaccid (low
      pressures) to tense (high pressures) membrane regime. The quality of the
      conventional methods for analysing data is evaluated using numerically generated
      data and a new method for data analysis, based on thermodynamic analysis and
      detailed statistical mechanical modelling, is introduced. The analysis of the
      classical method, where the membrane bending modulus is obtained from micro
      pipette aspiration data acquired in the low-pressure regime, reveals a
      significant correction from membrane stretching elasticity. The new description,
      which includes the full vesicle geometry and both the membrane bending and
      stretching elasticity, is used for the interpretation of micro-pipette aspiration
      experiments conducted on SOPC (stearoyl-oleoyl-phosphatidyl-choline) lipid
      vesicles in the fluid phase. The data analysis, which is extended by detailed
      image analysis and a fitting procedure based on Monte Carlo integration, gives an
      estimate of the bending modulus, that agrees with previously published results
      obtained by the use of shape fluctuation analysis of giant unilamellar vesicles.
      The obtained estimate of the area expansion modulus, is automatically corrected
      for contributions from residual thermal undulations and the equilibrium area of
      the vesicle is resolved.

PMID- 15254836
TI  - Dynamic domain formation in membranes: thickness-modulation-induced phase
      separation.
AB  - A simple model investigates the amplification of fluctuations on membranes
      constituted of two lipids having different lengths. Van der Waals and
      electrostatic interactions across the lipid bilayer result in a destabilization
      favoring thickness variations of the membrane. Close to spontaneous demixing of
      the two components, the additional gain in free energy due to thickness
      undulations shifts the stability boundary which promotes phase separation into
      domains. Interestingly, this effect can be induced by an applied electric field
      or membrane potential. In biological systems, the dynamic model presented here
      indicates that electric fields might be important for controlling phase
      separation and the formation of domains called "rafts".

PMID- 15254837
TI  - Where does a cohesive granular heap break?
AB  - In this paper, we consider the effect of cohesion on the stability of a granular
      heap and compute the maximum angle of stability of the heap as a function of the
      cohesion. We show that the stability is strongly affected by the dependence of
      the cohesion on the local pressure. In particular, this dependence is found to
      determine the localization of the failure plane. While for a constant adhesion
      force, slip occurs deep inside the heap, surface failure is obtained for a linear
      variation of the cohesion on the normal stress. Such a transition allows to
      interpret some recent experimental results on cohesive materials.

PMID- 15254838
TI  - Spectroscopic ellipsometry study of liquid crystal and polymeric thin films in
      visible and near infrared.
AB  - In this work, we propose spectroscopic ellipsometry as a suitable method for
      measuring optical properties in soft materials, polymers and liquid crystals,
      specially selected for use in photonics applications. We show the results of our
      measurements on some multilayered samples, in the range from visible to the near
      IR region, of interest for telecom applications. We point out potentialities and
      limits of the technique and compare the obtained results with another
      experimental method, the m-lines spectroscopy, and/or with existing data in the
      literature. The results about the optical parameters for the analysed materials
      (the nematic liquid crystal 5CB, one commercial and one lab made optical polymer,
      and an Indium Tin Oxide film) are useful and interesting by themselves. In fact,
      as a paradigmatic example, we briefly discuss how an incomplete knowledge of this
      kind of data can lead to a wrong design of a Bragg grating device. However, more
      than in the provided data, we put the interest of the present analysis in the
      warnings about spectroscopic ellipsometry utilization and eventually the
      necessity of getting complementary information.

PMID- 15254839
TI  - Interplay of surface and confinement effects on the molecular relaxation dynamics
      of nanoconfined poly(methyl methacrylate) chains.
AB  - The thermally stimulated current (TSC) signatures of the primary (alpha)
      transition and its precursor, the Johary-Goldstein (beta) relaxation, are used to
      probe effects of nanoconfinement on the dielectric relaxation dynamics of
      poly(methyl methacrylate) (PMMA) radically polymerised in situ 50 angstroms mean
      pore size silica-gel. Nanoconfinement leads to a broadened and low-temperature
      shifted beta band (peaking at Tbeta, with deltaTbeta = T(conf.)beta - T(bulk)beta
      = -15 degrees C for a heating rate of 5 deg/min), signifying the occurrence of
      faster relaxing moieties compared to the bulk-like PMMA film. Furthermore, both
      TSCs and differential scanning calorimetry (DSC) estimate a rise of the glass
      transition temperature for the confined phase ([Formula: see text]= +13 degrees
      C) and an increased width for the corresponding transition signals, relative to
      the signals in the bulk. Simple free-volume and entropy models seem inadequate to
      provide a collective description of the above perturbations. The observation of a
      spatial heterogeneity regarding the relaxation dynamics is discussed in terms of
      the presence of a motional gradient, with less mobile segments near the interface
      and more mobile segments in the core, and the interplay of adsorption ( e.g.,
      strong physical interactions that slow down molecular mobilities) and confinement
      effects ( e.g., lower entanglements concentration and local density fluctuations
      that provide regions of increased free space). The results suggest that in the
      case of high-molecular-weight polymers confined in small-pore systems, adsorption
      effects have considerable bearing on the glass transition phenomenon whereas
      confinement primarily influences side-chains' rotational mobilities. The
      confinement effect is expected to dominate over adsorption for PMMA phases
      occluded in higher pore sizes and silanised walls.

PMID- 15254840
TI  - Large-scale neural correlates of developmental dyslexia.
AB  - Recent work in the field of developmental dyslexia has emphasized the large-scale
      neural aspects of the disorder as measured by means of contemporary imaging
      techniques, electrophysiology, and post-mortem analyses. This article presents
      findings from these research domains and comprehensively reviews their relevance
      with respect to the behavioral and cognitive profiles of dyslexia. Large-scale
      alterations were observed in the perisylvian region across paradigms. Convergent
      evidence has also been reported in terms of hemispheric balance. Specifically,
      deviances in cerebral asymmetry associated with atypical organization of the left
      hemisphere were found in both children and adults with dyslexia. Emerging
      research encompassing high-temporal resolution methods such as
      magnetoencephalography (MEG) suggests right-hemisphere involvement and points to
      the complexity of the developmental disorder. A combined approach of structural
      imaging and MEG, and most importantly theory driven behavioral tasks may shed
      light on dynamics and trajectories of the neurobiology of dyslexia.

PMID- 15254841
TI  - Social impairment in Hyperkinetic Disorder - relationship to psychopathology and
      environmental stressors.
AB  - BACKGROUND: There is paucity of information concerning social impairment in
      children and adolescents referred to mental health services. AIMS: The aim of
      this study was to assess the association of social impairment, psychopathology
      and environmental stressors in Hyperkinetic Disorder (HKD) and to determine the
      frequency of pervasive developmental disorder (PDD) symptoms in HKD. METHOD:
      'Item sheets' about children and adolescents seen in child and adolescent mental
      health between 1992 and 2001 (n = 3644) were used to extract nine psychopathology
      domains, two social impairment subtypes and nine environmental stressors. The two
      social impairment subtypes were relationship difficulty (RD) and social
      communication difficulty (SCD) (i. e. autistic-like social impairment). The
      association of SCD/RD, psychopathology domains and environmental stressors was
      investigated in HKD cases and compared to a psychiatric control group. RESULTS:
      In children and adolescents with HKD, SCD was associated with speech and language
      difficulties, repetitive behaviour, developmental difficulties (all symptoms of
      PDD), affective symptoms, conduct problems and ADHD symptoms. Relationship
      difficulty was linked to conduct problems, affective symptoms and environmental
      stressors. Unlike SCD, RD was associated with all of the environmental stressors
      studied. There were significantly more children with PDD symptoms in the HKD
      group than in the control group. CONCLUSION: This study highlights the importance
      of subtyping social impairment in HKD and its association with psychopathology
      and environmental stressors. In HKD, SCD reflecting autistic social impairment is
      associated with other autistic symptoms, such as speech and language problems and
      repetitive behaviour. A small subgroup of HKD cases may have a milder form of
      autistic spectrum disorder.

PMID- 15254842
TI  - What are the characteristics of adolescent hospitalized suicide attempters?
AB  - AIM: To study the specificity of hospitalized adolescent suicide attempters.
      METHOD: Among a national sample of students (n = 11,718, mean age = 16.6 years)
      studied in 1999, 9.2% (n = 1078) made at least one suicide attempt during their
      life (SA); 21.9% (n = 234) of them were hospitalized (HSA). We identified the
      risk factors (family, school, behavioral and psychological) of SA and HSA by
      comparing (by gender) a) suicide attempters to non-suicide attempters and b)
      hospitalized suicide attempters to non-hospitalized suicide attempters. RESULTS:
      Both for girls and boys, the risk factors for SA varied. However, certain risk
      factors, particularly depressive mood, low self-esteem and poor parent-child
      relationships, were not associated with hospitalization. Hospitalized suicide
      attempters had more personal and social problems. But there is an important
      difference according to gender: in boys, hospitalization is related to physical
      fighting (OR = 2.2) and offences (OR = 3.4), in girls to running away (OR = 1.7),
      consumption of illegal drugs other than cannabis (OR = 2.0), having a living
      standard outside average (OR = 2.0) and going to a private school (OR = 1.7).
      CONCLUSION: Suicide attempters with problem behavior are more at risk of being
      hospitalized than others. However, the difference between hospitalized and non
      hospitalized subjects was smaller than expected.

PMID- 15254843
TI  - A prospective longitudinal study of early cognitive development in tuberous
      sclerosis - a clinic based study.
AB  - We report a prospective longitudinal study of cognitive development in a series
      of 20 clinic-referred infants with Tuberous Sclerosis. The infants were seen
      between the ages of 11 and 37 months and were assessed regularly at 6-month
      periods using a within-subjects repeated measures design. Assessment using the
      Mullen Scales of Early Learning, a measure of cognitive and motor showed that
      with the exception of one child, all children had composite developmental
      quotients that fell into the mentally retarded range of intellectual functioning.
      In general, the infants' developmental quotients changed little between 12 and 36
      months of age. Developmental progress was evident; however, with small
      incremental changes in raw scores for subjects over the course of the study. In
      three children, the developmental quotient changed by more than 20 points during
      the course of the study. The findings are considered in relation to the
      neurobiological risk factors for cognitive development in Tuberous Sclerosis.

PMID- 15254844
TI  - Psychopathological problems in children affected by tic disorders - study on a
      large Italian population.
AB  - AIM: The aim of this study was to assess the psychopathological and behavioural
      problems in patients affected by any tic disorder and their relationship with the
      severity of tic symptomatology. METHODS: A cross-sectional assessment was made of
      125 children and adolescents affected by any tic disorder, all at their first
      neuropsychiatric evaluation and all drug naive. Tic disorder diagnoses were
      established by using The Tourette Syndrome Classification Study Group criteria;
      the procedures included the administration of Yale Global Tic Severity Scale
      (YGTSS), Children Yale-Brown-Obsessive-Compulsive Scale (CY-BOCS) and Child
      Behaviour Checklist (CBCL). RESULTS: The patients showed a mild to moderate tic
      disorder (mean YGTSS score = 27). Of the patients, 19% had Obsessive-Compulsive
      Disorder (OCD), but another 46% showed Obsessive-Compulsive (OC) symptoms. CBCL T
      total was pathologic in 17% of the children, with higher percentages in the
      Internalization and Attention Problems subscales. Statistical analysis pointed
      out a significant relationship between YGTSS and CY-BOCS scores as well as a
      significant relationship between the duration of tic symptomatology and several
      CBCL subscales (Internalization, Depressed/Anxious, Thought and Attention
      Problems). CONCLUSION: Our data can be summarized in three main points: a large
      number of patients have milder tics without any psychopathological comorbidity;
      OC symptoms are frequently associated with tics, mainly in children with more
      severe symptomatology; psychopathological problems, in particular internalizing
      difficulties, are present in children with long standing tic disorders.

PMID- 15254845
TI  - Posttraumatic stress disorder following road traffic accidents - a second
      prospective study.
AB  - OBJECTIVE: The aim of this prospective study was to determine the psychological
      effects of everyday road traffic accidents (RTAs). METHODS: A community follow-up
      study was made of children (75 boys and 83 girls aged 7-18)-attending an Accident
      and Emergency Department after being involved in an RTA. Diagnostic clinical
      interview and self-completed psychometric assessments were performed. RESULTS:
      Four weeks post-accident diagnostic interviews revealed that 46 (29.1 %) children
      fulfilled the diagnostic criteria for posttraumatic stress disorder (PTSD).
      Screening questionnaires identified 20.3% with significant levels of anxiety and
      17.7% with scores above threshold levels for possible clinical depression. Type
      of accident, nature and severity of injury and age were not related to the
      development of PTSD. Gender was significant, with girls being more likely than
      boys to develop PTSD. CONCLUSION: Significant psychological distress following
      RTAs is common. The need to raise awareness of the possible psychological
      sequelae of everyday RTAs is highlighted.

PMID- 15254846
TI  - Combined psychopharmacological treatment among child and adolescent inpatients in
      Finland.
AB  - The aim of this study is to report the prevalence and factors associated with
      combined pharmacotherapy among child and adolescent psychiatric inpatients in
      Finland. The target group was all child and adolescent psychiatric inpatients at
      the beginning of the year 2000. Information about medication use was obtained for
      475 patients. The prevalence of combined pharmacotherapy was 16%. Of those taking
      pharmacotherapy, 36% had combined treatment. The most common combinations were
      neuroleptics and SSRIs. Most of the patients with combined pharmacotherapy had
      depressive or psychotic disorder. Among those with medication, older age (13-18
      years), psychotic disorder, bipolar disorder, low functioning level (CGAS > 40)
      and involuntary treatment were associated with combined treatment. Illness
      severity and treatment resistance were associated with combined pharmacotherapy.
      Further studies on indications, safety and efficacy of combined pharmacotherapy
      are warranted.

PMID- 15254847
TI  - The reliability and validity of the Oppositional Defiant Behavior Inventory.
AB  - OBJECTIVE: The aim of this study was to develop an evaluation scale for use as a
      supplementary tool for the diagnosis of oppositional defiant disorder (ODD).
      METHOD: The subjects were 98 Japanese children (91 males and 7 females), aged 6
      15 years, diagnosed with attention deficit/hyperactivity disorder (ADHD) or ODD.
      Internal consistency, test-retest reliability, concurrent validity and divergent
      validity of the oppositional defiant behavior inventory (ODBI), an evaluation
      scale of oppositional defiant tendency, were examined. RESULTS: Cronbach's alpha
      coefficient of the ODBI was 0.925. The correlation coefficient between the test
      and the retest was 0.820 (p < 0.0001). Both the ODBI scores (test and retest)
      were correlated with the number of items that matched the ODD diagnostic criteria
      of DSM-IV (r = 0.660, 0.659, p < 0.001), and with the ODD-scale of Disruptive
      Behavior Disorders Rating Scale (r = 0.725, 0.654, p < 0.001). Compared with the
      ADHD group or controls, the ADHD and ODD group showed a significantly higher ODBI
      score at p < 0.0001. CONCLUSION: The concurrent use of this scale with clinical
      examination is expected to increase the accuracy of the diagnosis of ODD.

PMID- 15254848
TI  - Effects of color stimulation on handwriting performance of children with ADHD
      without and with additional learning disabilities.
AB  - Active behavior problems in children with ADHD are often aggravated in situations
      which require sustained attention. Building on the 'optimal stimulation'
      hypothesis, this study explored the effects of color stimulation on graphomotor
      control in children with ADHD. A sample of 66 children with ADHD ( n = 19 from
      primary education, n = 28 children with additional speech disorders, n = 19
      children with additional learning disabilities) and matched controls participated
      in the investigation. Subjects performed a copying task on standard white and on
      colored paper in balanced order across classes. Positive effects of the color
      stimulation on graphomotor behavior control and, consequently, on qualitative
      aspects of the handwritings were expected. Results broadly confirm the
      predictions. Effects are explained as added external stimulation facilitating
      behavioral inhibition and regulation of selective attention and graphomotor
      coordination. Reduction of visual stress as an alternative explanation is
      considered.

PMID- 15254850
TI  - Uterine effects of the phytoestrogen 6-(1,1-dimethylallyl)naringenin in rats.
AB  - Phytoestrogens are discussed as candidate substances to treat symptoms related to
      estrogen deficiency. In in vitro experiments, the naturally occurring flavonoid 6
      (1,1-dimethylallyl)naringenin (6-DMAN) emerged as one of the most potent
      phytoestrogenic substances. 6-DMAN is not as well characterized as other
      flavonoids (8-prenylnaringenin) or isoflavones (genistein). We tested 6-DMAN for
      the first time in vivo, in a dose-dependent three-day uterotropic assay in
      ovariectomized Wistar rats, using 6-DMAN at three different concentrations (1.5
      mg/kg; 7.5 mg/kg and 15 mg/kg BW/d). Estradiol (E2; 10 microg/kg BW/d) and the
      carrier castor oil were used as positive and negative controls. 6-DMAN did not
      have any effect on uterine wet weight, while the positive control E2 did. In
      contrast, 6-DMAN stimulated uterine mRNA expression of estrogen responsive genes
      in ovariectomized rats. Estrogen receptor alpha and beta mRNA were expressed in
      the uterus. They mediate the expression of genes with an estrogen responsive
      element in the promoter, e. g., complement C3 and the progesterone receptor.
      Therefore, we analyzed the expression of the above-mentioned genes in three
      different concentrations. 6-DMAN up-regulated progesterone receptor and
      particularly complement C3 mRNA expression however, less pronounced than E2. In
      conclusion, we demonstrated for the first time estrogenic activities of 6-DMAN in
      vivo. Surprisingly, although 6-DMAN regulated estrogen responsive gene
      expression, there was no uterine wet weight gain. These findings make 6-DMAN a
      very interesting candidate substance for further characterization, as it
      potentially represents a naturally occurring selective estrogen receptor
      modulator.

PMID- 15254851
TI  - The fixed combination of valerian and hops (Ze91019) acts via a central adenosine
      mechanism.
AB  - The aim of the study was to demonstrate competition between caffeine and a fixed
      valerian/hop extract combination (Ze91019) by the central adenosine mechanism.
      EEG was used to describe the action of caffeine on the central nervous system
      after oral administration (200 mg) in healthy volunteers. In addition to
      caffeine, the volunteers (16 in each group) received either placebo or verum (2
      and 6 tablets containing the valerian/hop extract). The EEG responses were
      recorded every 30 min thereafter. The verum medication was capable of reducing (2
      tablets) or inhibiting (6 tablets) the arousal induced by caffeine. This
      pharmacodynamic action was observed 60 minutes after oral administration,
      indicating not only competition between the antagonist caffeine and the partial
      agonist, i. e., the valerian/hop extract but also bio-availability of the
      compound(s) responsible for the agonistic action. In conclusion, the valerian/hop
      extract acts via a central adenosine mechanism which is possibly the reason for
      its sleep-inducing and -maintaining activity.

PMID- 15254852
TI  - Vascular activity of (-)-anonaine, (-)-roemerine and (-)-pukateine, three natural
      6a(R)-1,2-methylenedioxyaporphines with different affinities for alpha1
      adrenoceptor subtypes.
AB  - We have studied the mechanism of action of three 6a( R)-1,2
      methylenedioxyaporphines as vasorelaxant compounds. The alkaloids assayed showed
      different affinities for the three human cloned alpha (1)-adrenoceptor (AR)
      subtypes stably expressed in rat-1 fibroblasts, showing lower affinity for
      alpha(1B)-AR with regard to the alpha(1A)- or alpha(1D)-subtypes. These three
      natural compounds are more potent inhibitors of [ (3)H]-prazosin binding than of
      [ (3)H]-diltiazem binding to rat cerebral cortical membranes. As all these
      alkaloids inhibited noradrenaline (NA)-induced [ (3)H]-inositol phosphate
      formation in cerebral cortex and rat tail artery, they may be safely viewed as
      alpha (1)-AR antagonists, as is demonstrated by the vasorelaxant responses
      observed in isolated rat tail artery and/or aorta precontracted with NA. The
      alkaloids also inhibited the contractile response evoked by KCl (80 mM) but with
      a lower potency than that shown against NA-induced contraction. We have also
      examined their ability to inhibit the different forms of cyclic nucleotide
      phosphodiesterases (PDE) isolated from bovine aortic smooth muscle and
      endothelial cells, with negative results. We conclude that N-methylation favours
      the interaction of (R)-aporphines with all alpha (1)-AR subtypes, and that the
      topography of the binding site recognizing the basic or protonated nitrogen atom
      is similar in all three alpha (1)-AR subtypes. The presence of a hydroxy group at
      C-11 has different effects on the affinity for each alpha (1)-AR subtype but
      decreases the affinity for Ca (2+) channels. These results confirm and extend the
      view that subtle changes in the hydroxylation patterns on the aromatic ring of
      the aporphine structure affect the interactions of these compounds with the three
      alpha (1)-AR subtypes in different ways, suggesting that the binding site
      recognizing the aporphine skeleton is different in each of the three subtypes.

PMID- 15254853
TI  - Activation of alpha1A-adrenoceptors by genistein at concentrations lower than
      that to inhibit tyrosine kinase in cultured C2C12 cells.
AB  - Genistein, an isoflavonoid natural product, is widely used to inhibit protein
      tyrosine kinase (PTK). In the present study, we investigated the possible
      influence of genistein on alpha (1)-adrenoceptors (AR) in cultured C2C12 cells.
      Genistein enhanced the uptake of radioactive glucose into C2C12 cells in a
      concentration-dependent manner. Similar results were also observed in samples
      treated with daidzein, the inactive congener for PTK inhibition. The effect of
      genistein on alpha (1)-AR was further characterized using the displacement of [
      (3)H]prazosin binding in C2C12 cells. The increase in radioactive glucose uptake
      by genistein was abolished by RS17053 at a concentration sufficient to block
      alpha (1A)-AR. The pharmacological inhibition of phospholipase C (PLC) by U73122
      resulted in a concentration-dependent reduction of genistein-stimulated glucose
      uptake in C2C12 cells. This inhibition by U73122 was specific because the
      inactive congener, U73343, failed to modify the action of genistein. Moreover,
      genistein can activate alpha (1A)-AR at a concentration (1 micromol/L) lower than
      that (50 micromol/L) needed to abolish the insulin-stimulated phosphorylation of
      PTK. The obtained data indicate an activation of alpha (1A)-AR by genistein to
      increase the glucose uptake into C2C12 cells and this supports the application of
      genistein as a TK inhibitor.

PMID- 15254854
TI  - Inhibition of Helicobacter pylori adhesion to human gastric adenocarcinoma
      epithelial cells by acidic polysaccharides from Artemisia capillaris and Panax
      ginseng.
AB  - Helicobacter pylori specifically adheres to host cells, mainly based on
      carbohydrate-mediated cell-cell interactions. Previously, we investigated the
      anti-adhesive effect of polysaccharide fractions from Artemisia capillaris and
      Panax ginseng, using hemagglutination and enzyme-linked glycosorbent assays. In
      the present study, each active polysaccharide fraction was further purified,
      resulting in a single peak (fraction F2) using gel filtration FPLC, in which no
      protein content was detectable. Using scanning electron microscopy, we examined
      the inhibitory effects of these polysaccharides on the attachment of H. pylori to
      the human gastric adenocarcinoma epithelial cell line. The bacterial attachment
      to the cell line was inhibited by these polysaccharides in the range of the
      concentrations studied (0.2 - 2.8 mg/mL), showing their minimum inhibitory
      concentration at as low as 0.2 mg/mL. The bacterial binding was inhibited more
      effectively by P. ginseng polysaccharides, than by those from A. capillaris. The
      purified polysaccharides contain similar sugar compositions and have high amounts
      of uronic acids. Our results suggest that acidic carbohydrates may play an
      important role in the inhibitory activity on H. pylori adhesion to host cells and
      that our established purification protocol can be applied to obtain active acidic
      polysaccharides from plant sources.

PMID- 15254855
TI  - High molecular weight polysaccharides from black currant seeds inhibit adhesion
      of Helicobacter pylori to human gastric mucosa.
AB  - Several crude and purified polysaccharides from black currant seeds (Ribes nigrum
      L.) have been isolated, analysed and examined on their effects against
      Helicobacter pylori in in situ adhesion studies on sections of human gastric
      mucosa. After pre-treatment of Helicobacter pylori with 0.01 to 0.1 % solutions
      of the isolated raw polysaccharide (RPS), the epithelial binding of the bacteria
      was considerably reduced in a concentration-dependent manner, as compared with a
      non-treated control suspension. Preincubation of the mucosal sections with 0.1 %
      solutions did not result in a reduced binding of non-treated bacteria. An anion
      exchange fraction of RPS eluted with 0.1 M phosphate buffer exhibited a
      comparable, concentration-dependent reduction of adhesion, whereas the water
      eluted fraction was ineffective at the respective concentrations. Both
      subfractions consisted of similar 1,3-linked galactans, decorated with side
      chains possessing 1,4-galacturonic acid, galactose and arabinose residues.
      Molecular weight profiling by GPC revealed that the antiadhesive activity of the
      buffer eluate correlated with high molecular weight components ranging from about
      1000 Da to 340 kDa, whereas the ones of the inactive water eluate had molecular
      weights of about 100 and 25 kDa, respectively. None of the active fractions
      revealed inhibitory effects on bacterial growth in vitro. We conclude that
      acidic, high molecular weight galactans are responsible for the antiadhesive
      qualities of black currant seed extracts and that these polymers are able to
      block Helicobacter surface receptors, thus inhibiting their interaction with
      specific binding factors located on human gastric epithelia.

PMID- 15254856
TI  - Microbial metabolism of pseudoprotodioscin.
AB  - Microbial transformation of the furostanol saponin pseudoprotodioscin ( 1) using
      Aspergillus fumigatus resulted in the isolation of two new steroidal metabolites,
      3- O-[bis- alpha- L-rhamnopyranosyl-(1-->2 and 1-->4)- beta- D-glucopyranosyl]-22
      R,25 R-spirost-5-ene-3 beta,20 alpha-diol ( 2) and 3- O-[bis- alpha- L
      rhamnopyranosyl-(1-->2 and 1-->4)- beta- D-glucopyranosyl]-25 R-furost-5-ene-3
      beta,22 alpha,26-triol ( 3), in addition to the previously reported steroidal
      saponins: dioscin ( 4) and progenin II ( 5). The structure elucidation of these
      metabolites was based primarily on 1D and 2D NMR analyses. Metabolites 2 - 5
      showed significant cytotoxicity against cancer cell lines A375, L929, and HeLa
      with IC (50) values ranging from 1.18 microM to 17.88 microM.

PMID- 15254857
TI  - Tryptanthrin content in Isatis tinctoria leaves--a comparative study of selected
      strains and post-harvest treatments.
AB  - Tryptanthrin is a pharmacologically active compound in the anti-inflammatory herb
      Isatis tinctoria, with potent inhibitory activity on prostaglandin and
      leukotriene synthesis and on inducible NO synthase. The tryptanthrin content of
      five defined woad strains was analyzed in dependence of the time of harvest and
      post-harvest treatment. Tryptanthrin was determined by a validated ESI-LC-MS
      isotope dilution assay with d(8)-tryptanthrin as internal standard. The
      tryptanthrin concentration in freeze-dried leaf samples was low. Drying at
      ambient temperature led to a significant increase of tryptanthrin concentration,
      but the highest concentrations were found when leaves were dried at 40 degrees C.
      Tryptanthrin content in fermented woad leaves was below the limit of
      quantification. Tryptanthrin appears thus to be a product of post-harvest
      processes, but details of its formation remain to be elucidated.

PMID- 15254858
TI  - New sesquiterpenes with intestinal relaxant effect from Celastrus paniculatus.
AB  - The seed oil obtained from Celastrus paniculatus has been used in Ayurvedic
      medicine for the treatment of several complaints including intestinal disorders.
      The muscle relaxing activity of C. paniculatus has been studied in vitro on
      isolated preparations of rat intestine. C. paniculatus seeds extract (0.001 - 100
      microg/mL) produced a concentration-related relaxation of the rat ileum [IC (50)
      (95 % c. l.) 0.24 (0.13 - 0.45) microg/mL]. Among the four fractions ( n-hexane,
      CCl (4), CHCl (3), n-BuOH) obtained from the methanolic extract of C.
      paniculatus, only the carbon tetrachloride fraction (0.01 - 10 000 ng/mL) induced
      a significant relaxation of the intestinal muscle [IC (50) (95 % c. l.): 1.9
      (1.38 - 2.87) ng/mL]. Three new sesquiterpene polyol esters have been isolated
      from the carbon tetrachloride fraction. These new metabolites, characterised as
      1alpha,8beta,14-triacetoxy-9beta-furoyloxydihydro-beta-agarofuran ( 1), 1alpha,
      6beta,8beta,14-tetraacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 2) and
      1alpha,8beta-diacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 3), at the
      concentration of 1 microg/mL produced a relaxant effect of 30.6 +/- 12.2 %, 26.9
      +/- 4.7 % and 7.27 +/- 1.7 %, respectively.

PMID- 15254859
TI  - Structure-activity relationships for euphocharacins A-L, a new series of
      jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein.
AB  - The Mediterranean spurge Euphorbia characias L. afforded twelve new diterpenes
      based on a jatrophane skeleton named euphocharacins A-L. Their chemical
      structures were elucidated by extensive nuclear magnetic resonance and mass
      spectrometry methods. Euphocharacins A-L were tested as inhibitors of the
      daunomycin-efflux activity of P-glycoprotein from cancer cells. The results were
      used to extend the structure-activity relationship established for this class of
      compounds, highlighting the positive effects of propyl and benzoyl groups at
      positions 3 and 9, respectively, and evidencing the negative effect of a free
      hydroxyl group at position 2. Among the tested compounds, euphocharacins C and I
      showed an activity higher than cyclosporin to inhibit Pgp-mediated daunomycin
      transport.

PMID- 15254860
TI  - Guineensine, an Acyl-CoA: cholesterol acyltransferase inhibitor, from the fruits
      of Piper longum.
AB  - Bioactivity-guided fractionations for ACAT inhibitor led to the isolation of
      guineensine from the CHCl (3) extract of Piper longum. Its structure was
      identified by spectroscopic means (IR, UV, MS and NMR). Guineensine inhibited
      ACAT activity in a dose-dependent manner with an IC (50) value of 3.12 micro M.

PMID- 15254862
TI  - Tumor microenvironmental physiology and its implications for radiation oncology.
AB  - The microenvironmental physiology of tumors is uniquely different from that of
      normal tissues. It is characterized, inter alia, by O(2) depletion (hypoxia,
      anoxia), glucose and energy deprivation, high lactate levels, and extracellular
      acidosis, parameters that are anisotropically distributed within the tumor mass.
      This hostile microenvironment is largely dictated by the abnormal tumor
      vasculature and heterogeneous microcirculation. Hypoxia and other hostile
      microenvironmental parameters are known to directly or indirectly confer
      resistance to irradiation leading to treatment failure. Hypoxia directly leads to
      a reduced "fixation" of radiation-induced DNA damage. Indirect mechanisms include
      a restrained proliferation, changes in gene expression and alterations of the
      proteome (eg, elevated activity of DNA-repair enzymes and resistance-related
      proteins, increased transcription of growth factors), and genomic changes
      (genomic instability leading to clonal heterogeneity and selection of resistant
      clonal variants). These changes, caused by the hostile microenvironment, can
      favor tumor progression and acquired treatment resistance, both resulting in poor
      clinical outcome and prognosis. Pretreatment assessment of critical
      microenvironmental parameters is therefore needed to allow the selection of
      patients who could benefit from special treatment approaches (eg, hypoxia
      targeting therapy). Because of a relatively high risk of local relapse or distant
      metastasis, patients with hypoxic and/or "high-lactate" tumors should undergo
      close surveillance.

PMID- 15254863
TI  - The hypoxic tumor microenvironment and gene expression.
AB  - Solid tumors are not static entities but are constantly responding to
      environmental signals as they grow and develop. One mechanism by which they
      respond to the adverse conditions of the tumor microenvironment is through
      coordinated changes in gene expression. The synchronized turning of genes on and
      off leads to biologic adaption to the adverse oxygen-poor environment. Because
      tumor hypoxia can be found in almost every solid tumor, it represents one of the
      most pervasive microenvironmental stresses that can impact malignant progression
      and therapeutic response. Interestingly, tumors that exhibit robust induction of
      hypoxia-responsive gene expression networks show a clinically more aggressive
      natural history. The contribution of hypoxia-responsive gene networks to
      malignant response is currently under investigation. An understanding of the
      coordinated functions of hypoxia induced and repressed genes can lead to a better
      understanding of the clinical significance of the hypoxic tumor phenotype.

PMID- 15254864
TI  - The relationship between hypoxia and angiogenesis.
AB  - Recent studies have generated a large amount of data supporting the hypothesis
      that hypoxia drives tumor angiogenesis. The relationship between the two is often
      considered a matter of supply and demand: ineffectively-vascularized tumor tissue
      becomes hypoxic, stimulating neoangiogenesis to improve the influx of oxygen,
      thereby diminishing the angiogenic drive. Although this paradigm is logically
      pleasing, much of what is known about tumor biology argues against such a
      straightforward relationship. In fact, some preclinical data convincingly shows
      that tumor hypoxia and angiogenesis do not always go hand in hand. It is
      important to begin to explore means of reconciling these discrepancies. Although
      poor oxygenation is a strong stimulus for tumor angiogenesis, (1) the
      pathogenesis of tumor hypoxia is much more complicated than the supply-demand
      paradigm lets on and (2) hypoxia is not necessarily sufficient or necessary for
      neovascularization to occur. These subtleties may help to explain why so much
      data disagrees with the current hypoxia-angiogenesis model and may begin to build
      a better understanding of the role hypoxia plays in tumor vascularization. This
      article will review what is known about hypoxia and angiogenesis in
      nononcological processes and will apply these lessons to tumor biology to more
      deeply describe their relationship.

PMID- 15254865
TI  - Therapeutic targeting of the tumor vasculature.
AB  - A functional tumor vasculature is essential for tumor growth and metastasis and
      makes an attractive target for therapy. Both antiangiogenic and antivascular
      approaches are being developed for this purpose. In this article, the current
      antiangiogenic and antivascular approaches to cancer therapy, potential for their
      combination with radiotherapy, methods for identifying new targets on the tumor
      vasculature, and methods for evaluating new vascular-targeted strategies in in
      vivo model systems are reviewed.

PMID- 15254866
TI  - Clinical studies of hypoxia modification in radiotherapy.
AB  - Hypoxic modification has been the subject of investigations in clinical radiation
      oncology since the early 60s. To date, this has not yet resulted in a treatment
      that has been widely accepted. Logistics and technical difficulties limit the
      routine use of hyperbaric oxygen in radiotherapy. The nitroimidazoles have not
      gained general acceptance, initially because of their toxicity and later because
      of doubts about the effectiveness of the newer generation of less toxic drugs.
      Nevertheless, there is good evidence from these studies that improving clinical
      outcome by hypoxic modulation is an achievable goal. Newer approaches including
      combinations of radiotherapy with tirapazamine, erythropoietin, and carbogen and
      nicotinamide (ARCON) are currently in phase III trial. For these new strategies
      to be successful, it is important that the proper patient categories are
      selected. Various methods to assess tumor oxygenation are now becoming available
      in the clinic. These potential predictive assays must be incorporated and
      validated in current and future large-scale clinical trials. Modifiers that
      target other aspects of tumor biology may also have indirect effects on tumor
      oxygenation. These aspects require further study in preclinical and early
      clinical settings.

PMID- 15254867
TI  - Measurement of tumor hypoxia using single-cell methods.
AB  - A growing appreciation for the importance of hypoxia in tumor progression and
      response to treatment has driven efforts to develop methods that could be used
      routinely in the clinic to identify tumors containing hypoxic cells. The ideal
      method would be noninvasive and could be used both before treatment to determine
      the presence of hypoxia and during therapy to assess tumor reoxygenation.
      Although this goal is being approached, there are still questions about how best
      to measure tumor oxygenation and whether noninvasive imaging methods can provide
      the necessary sensitivity. Analysis of hypoxia at the level of the individual
      cell can provide the following information that cannot be obtained in other ways:
      the degree of hypoxia, the lifetime of hypoxic cells, and the dynamic nature of
      hypoxia. This review will describe methods that have been used to detect hypoxia
      in individual cells, the relation between these measurements and patient response
      to treatment, and indicate where these methods can provide important additional
      insights into the consequences of tumor hypoxia.

PMID- 15254868
TI  - The human tumor microenvironment: invasive (needle) measurement of oxygen and
      interstitial fluid pressure.
AB  - Invasive needle-based assessments of the extracellular environment in human
      tumors have yielded important prognostic information that has shaped the
      direction of future translational research and begun to influence clinical
      practice. This review focuses on electrode measurements of oxygenation in human
      tumors, particularly in relation to the practicalities of applying these
      techniques in the clinic and the relationship to patient outcome. Elevated tumor
      interstitial fluid pressure (IFP) has been shown to be an important independent
      prognostic factor in cervix cancer. The pathophysiology of elevated IFP is
      discussed, along with possible explanations for the strong influence on patient
      outcome and directions for future research.

PMID- 15254869
TI  - Oxidative stress, redox, and the tumor microenvironment.
AB  - Cellular metabolism is critical for the generation of energy in biological
      systems; however, as a result of electron transfer reactions, reactive oxygen
      species (ROS) are generated in aerobic cells. Although low amounts of ROS are
      easily tolerated by the cell, abnormally high levels of ROS induce oxidative
      stress. ROS are also produced after exposure to ionizing radiation, selected
      chemotherapeutic agents, hyperthermia, inhibition of antioxidant enzymes, or
      depletion of cellular reductants such as NADPH and glutathione. Oxidative stress
      such as ionizing radiation produces a variety of highly reactive free radicals
      that damage cells, initiate signal transduction pathways, and alter gene
      expression. Cells are capable of countering the effects of oxidative stress by
      virtue of a complex redox buffering system. With respect to the radiation
      treatment of cancer, components of the cellular redox armamentarium may be
      targeted to enhance cell killing in the case of tumors and/or protection in the
      case of normal tissues.

PMID- 15254870
TI  - Lactate: mirror and motor of tumor malignancy.
AB  - A number of studies have shown that malignant transformation is associated with
      an increase in glycolytic flux and in anaerobic and aerobic cellular lactate
      excretion. Using quantitative bioluminescence imaging in various primary
      carcinomas in patients (uterine cervix, head and neck, colorectal region) at
      first diagnosis of the disease, we showed that lactate concentrations in tumors
      in vivo can be relatively low or extremely high (up to 40 micromol/g) in
      different individual tumors or within the same lesion. In all tumor entities
      investigated, high concentrations of lactate were correlated with a high
      incidence of distant metastasis already in an early stage of the disease. Low
      lactate tumors (<median of approximately 8 micromol/g) were associated with both
      a longer overall and disease-free survival compared with high lactate lesions (>8
      micromol/g). Lactate dehydrogenase was found to be upregulated in most of these
      tumors compared with surrounding normal tissue. Numerous recent reports support
      these data by showing various biological activities of lactate that can enhance
      the malignant behavior of cancer cells. These mechanisms include the activation
      of hyaluronan synthesis by tumor-associated fibroblasts, upregulation of vascular
      endothelial growth factor and of hypoxia-inducible factor 1alpha, and direct
      enhancement of cellular motility that generates favorable conditions for
      metastatic spread. Thus, lactate accumulation not only mirrors but also actively
      enhances the degree of tumor malignancy. We propose that determination of lactate
      in primary tumors may serve as a basis of a novel metabolic classification, which
      can lead to an improvement of prognosis and therapy in clinical oncology.

PMID- 15254872
TI  - Insulin secretion and insulin sensitivity at different stages of glucose
      tolerance: a cross-sectional study of Japanese type 2 diabetes.
AB  - To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan,
      insulin secretion and insulin sensitivity were compared across the range of
      glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance
      (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to
      the criteria of the World Health Organization (WHO). We examined insulin
      secretion and insulin sensitivity using fasting blood glucose and insulin levels
      and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment
      (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin
      secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI)
      composite for insulin sensitivity. Although insulin resistance plays an important
      role in the development of diabetes in many ethnic populations, the differences
      in insulin sensitivity between NGT and IGT and between IGT and DM are small in
      Japanese patients. On the other hand, as glucose intolerance increases, insulin
      secretion decreases most remarkably both between NGT and IGT and between IGT and
      DM in Japanese patients. Decreasing insulin secretion and decreasing insulin
      sensitivity both occur in developing type 2 diabetes in Japanese patients, but
      decreased basal and early-phase insulin secretion had more pronounced
      contribution to glucose tolerance than the indices of insulin sensitivity.
      Japanese type 2 diabetic patients are characterized by a larger decrease in
      insulin secretion and show less attribution of insulin resistance.

PMID- 15254873
TI  - Physical exercise enhances hepatic insulin signaling and inhibits
      phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus.
AB  - We have shown that physical exercise enhances insulin sensitivity of skeletal
      muscle in diabetes-prone Psammomys-obesus. In this study, we examined the effect
      of physical exercise on the liver of these animals. Three groups of animals were
      exposed to a 4-week protocol; high-energy diet (CH), high-energy diet and
      exercising (EH), and low-energy diet (CL). Different groups were studied either
      in a fed state or after an overnight fast, 30 minutes after intraperitoneal (IP)
      injection of 1 U insulin. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and
      glucose-6-phosphatase (G6Pase) activity was measured. Insulin signaling response
      was examined after insulin injection in the fast state by analyzing tyrosine
      phosphorylation of insulin receptor (IR) and the association between insulin
      receptor substrate-1 (IRS-1) and IRS-2 with phosphatidylinositol 3 kinase (PI3
      K). After 4 weeks, none of the EH animals became diabetic, whereas all the CH
      animals became diabetic. PEPCK activity in the fed state was higher in the CH
      group compared with the CL and EH groups (480 +/- 28 nmol/min/mg protein, 280 +/-
      30 nmol/min/mg protein, and 208 +/- 13 nmol/min/mg protein, respectively) (P <
      .02). G6Pase activity was higher in the CH and EH groups compared with the CL
      group (261 +/- 54 nmol/min/mg protein, 251 +/- 34 nmol/min/mg protein, and 75 +/-
      32 nmol/min/mg protein, respectively) (P < .01). After insulin administration in
      the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3
      K were higher in the EH and CL groups than in the CH group. We conclude that
      exercise improves in vivo hepatic insulin sensitivity in diabetes-prone Psammomys
      obesus.

PMID- 15254874
TI  - Altered mouse cholinephosphotransferase gene expression in kidneys of type 2
      diabetic KK/TA mouse.
AB  - It is generally considered that genetic factors may contribute to the
      susceptibility of type 2 diabetic nephropathy. The purpose of the present study
      is to identify molecules that contribute to the development and/or progression of
      this disease. Differential display was performed to isolate genes in the kidney
      using the KK/Ta mouse model of type 2 diabetes. The differential expression of 8
      randomly chosen candidate genes (DN1-8) were verified by reverse-transcriptase
      polymerase chain reaction (RT-PCR) or Northern blot analysis. DN1-3 (Zn-alpha2
      glycoprotein, vascular endothelial growth factor receptor [VEGFR]-2, and lactate
      dehydrogenase [LDH]) were overexpressed and DN7-8 (peroxisome proliferator
      activated receptor [PPAR]-interacting protein [PRIP], unknown) were
      underexpressed in the KK/Ta mouse kidney. DN4-6 (Ezrin, transcobalamin 2, aldo
      ketoreductase) did not differ between KK/Ta and control (BALB/c) mice. DN8 only
      showed no significant sequence similarity to previously reported genes. Molecular
      cloning revealed that full-length DN8 shares 89% identity with human
      cholinephosphotransferase 1 (hCHPT1), and we designated it as "putative" mouse
      cholinephosphotransferase 1 (mCHPT1). The putative mCHPT1 gene was most closely
      mapped to the D10Mit94 locus with the highest logarithm of odds (lod) score. In
      situ hybridization revealed the levels of glomerular putative mCHPT1 in BALB/c
      mice tended to be slightly higher than those in KK/Ta mice. The altered renal
      mRNA expression of these genes may be involved in the development and/or
      progression of diabetic nephropathy.

PMID- 15254875
TI  - Metabolism of oral glucose in children born small for gestational age: evidence
      for an impaired whole body glucose oxidation.
AB  - Epidemiological studies indicate that intrauterine growth restriction confers an
      increased risk of developing type 2 diabetes mellitus in subsequent life. Several
      studies have further documented the presence of insulin resistance in young
      adults or adolescent children born small for gestational age. Since most studies
      addressed postpubertal individuals, and since puberty markedly affects energy
      metabolism, we evaluated the disposal of oral glucose in a group including mainly
      prepubertal and early pubertal children with intrauterine growth restriction and
      in healthy age- and weight-matched control children. All children had an
      evaluation of their body composition by skinfold thickness measurements. They
      were then studied in standardized conditions and received 4 consecutive hourly
      loads of 180 mg glucose/kg body weight to reach a near steady state. Energy
      expenditure and substrate oxidation were evaluated during the fourth hour by
      indirect calorimetry. Compared to both age- and weight-matched children, children
      born small for gestational age had lower stature. Their energy expenditure was
      not significantly decreased, but they had lower glucose oxidation rates. These
      results indicate that metabolic alterations are present early in children born
      small for gestational age, and are possibly related to alterations of body
      composition.

PMID- 15254876
TI  - Low-grade inflammation may play a role in the etiology of the metabolic syndrome
      in patients with coronary heart disease: the HIFMECH study.
AB  - Risk of coronary heart disease has been related to insulin resistance, but the
      mechanism for this is incompletely understood. Variables attributed to insulin
      resistance are associated with low-grade inflammation. A case-control study was
      performed of 469 male myocardial infarction (MI) survivors aged < 60 years and
      575 control subjects recruited from centers in northern and southern Europe.
      Principal factor analysis was used to explore correlations between insulin
      resistance and inflammatory variables. Three factors resulted: (a) "Metabolic
      Syndrome" (insulin/proinsulin/ triglyceride/body mass index [BMI]); (b)
      "Inflammation" (fibrinogen/C-reactive protein [CRP]/interleukin-6 [IL-6]); and
      (c) "Blood Pressure" (systolic and diastolic blood pressure). The "Metabolic
      Syndrome" factor was related to the "Inflammation" factor (largely independently
      of obesity), the "Blood Pressure" factor, smoking, and south location (all P < or
      = .0002). There were significant relationships between all 3 factors and case
      status (P < or = .0002). Markers of low-grade inflammation are strongly related
      to metabolic syndrome variables independently of obesity. This raises the
      possibility that links between insulin resistance and cardiovascular disease
      could, in part, represent common consequences of low-grade inflammation.

PMID- 15254877
TI  - Smoking prevents the intravascular remodeling of high-density lipoprotein
      particles: implications for reverse cholesterol transport.
AB  - Smoking is a leading cause of atherosclerosis acting trough a wide spectrum of
      mechanisms, notably the increase of the proatherogenic effect of dyslipidemia.
      However, a severe atherosclerotic disease is frequently observed in smokers who
      do not present an overt dyslipidemia. In the present study, we sought to
      determine if abnormalities in lipid metabolism occur in normolipidemic smokers,
      focusing especially on the components of intravascular remodeling of high-density
      lipoprotein (HDL) For this purpose, we measured lipid transfer proteins and
      enzymes involved in the reverse cholesterol transport (RCT) system in 29 adults:
      15 smokers and 14 controls. The blood samples were drawn in the fasting state,
      immediately after the smokers smoked 1 cigarette. The composition of HDL
      particles was analyzed after isolation of HDL fractions by
      microultracentrifugation. We observed that normolipidemic smokers present higher
      total plasma and HDL phospholipids (PL) (P < .05), 30% lower postheparin hepatic
      lipase (HL) activity (P < .01), and 40% lower phospholipid transfer protein
      (PLTP) activity (P < .01), as compared with nonsmokers. The plasma cholesteryl
      ester transfer protein (CETP) mass was 17% higher in smokers as compared with
      controls (P < .05), but the endogenous CETP activity corrected for plasma
      triglycerides (TG) was in fact 57% lower in smokers than in controls (P < .01).
      Lipid transfer inhibitor protein activity was also similar in both groups. In
      conclusion, the habit of smoking induces a severe impairment of many steps of the
      RCT system even in the absence of overt dyslipidemia. Such an adverse effect
      might favor the atherogenicity of smoking.

PMID- 15254878
TI  - Serum tumor necrosis factor-alpha levels and components of the metabolic syndrome
      in obese adolescents.
AB  - Tumor necrosis factor-alpha (TNF-alpha) seems to be increased in obese subjects,
      suggesting its role as a proinflammatory cytokine to insulin resistance and
      metabolic abnormalities in obesity. The aim of this study was to evaluate the
      relationship between serum TNF-alpha, soluble TNF-alpha receptor 1 (sTNF-R1), TNF
      alpha receptor 2 (sTNF-R2), and metabolic syndrome (MS) components and
      anthropometric indices in obese and non-obese adolescents. A cross-sectional
      study was performed on obese and non-obese adolescents. We studied 71 adolescents
      (age, 15 to 16 years old); 39 were obese (obese group; 14 males and 25 females)
      and 32 were non-obese adolescents (non-obese lean group; 12 males and 20
      females). The body mass index (BMI), waist circumference (WC), waist-to-hip ratio
      (WHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were
      determined in each subject. The serum TNF-alpha, sTNF-R1, sTNF-R2, fasting plasma
      glucose (FPG), and lipid profile were also measured. The mean serum TNF-alpha,
      sTNF-R1, and sTNF-R2 were significantly higher in the obese than the non-obese
      group (TNF-alpha, 18.15 v 5.88 pg/mL, P < .001; sTNF-R1, 2.01 v 1.40 ng/mL, P <
      .001; sTNF-R2, 6.06 v 3.70 pg/mL, P < .001). The serum TNF-alpha concentrations
      were positively correlated with the BMI (TNF-alpha, r = 0.346, P < .05; sTNF-R1,
      r = 0.624, P < .001; sTNF-R2, r = 0.482, P < .001, respectively) and WC (TNF
      alpha, r = 0.525, P < .05; sTNF-R1, r = 0.700, P < .001; sTNF-R2, r = 0.669, P <
      .001, respectively). The serum TNF-alpha was positively correlated with
      triglyceride (TG) and DBP, and negatively with high-density lipoprotein
      cholesterol (HDLC). The sTNF-R1 and sTNF-R2 were correlated with TG and DBP, and
      TG, respectively. Obese compared with non-obese adolescents exhibited higher
      concentrations of TNF-alpha and its soluble receptors, and the higher TNF-alpha
      concentrations were associated with several components of MS in obese
      adolescents.

PMID- 15254879
TI  - High glucose augments arginase activity and nitric oxide production in the renal
      cortex.
AB  - To clarify the interaction between arginase and nitric oxide (NO) production in
      the kidney with normal and high glucose levels, renal cortical slices from male
      Sprague-Dawley rats were incubated in Hank's solution containing various
      concentrations of L-norvaline (Nval; an arginase inhibitor), 500 U/mL superoxide
      dismutase, and either 5 mmol/L (normal) or 20 mmol/L (high) glucose (n = 5 per
      group). Incubation with Nval increased renal cortical NOX (nitrite + nitrate)
      production dose-dependently, indicating competition between arginase and NO
      synthase (NOS) for the substrate (L-arginine). In the basal condition without
      Nval, high glucose also increased NO(X) production to a rate 3 times that
      observed during incubation with normal glucose (P < .01). This effect of high
      glucose was not altered by Nval. Rather, the effects of high glucose and Nval
      were additive, indicating that the activity of NOS per se is enhanced by high
      glucose. Direct assay of arginase and NOS activities confirmed stimulation of
      both enzymes under the high glucose condition (P < .05, P < .01, v normal
      glucose, respectively). However, high glucose did not change the amount of L
      arginine present in renal cortical slices. These data reveal that arginase
      competes with NOS for L-arginine in the renal cortex, and that high glucose
      increases the activity of both enzymes without affecting the amount of substrate.
      These results suggest that increased NOS activity, rather than altered substrate
      availability, may be the principal factor underlying increased NO synthesis in
      diabetic kidneys.

PMID- 15254880
TI  - Are peristaltic pumps as reliable as syringe pumps for metabolic research?
      Assessment of accuracy, precision, and metabolic kinetics.
AB  - Syringe pumps are traditionally used to infuse tracers in metabolic research
      because they are perceived to be more accurate and precise than peristaltic
      pumps. This study evaluated the accuracy (actual v programmed infusion rate) and
      precision (reproducibility of infusion) of a peristaltic pump (Gemini PC 2; IMED,
      San Diego, CA) and a syringe pump (Model 22; Harvard Apparatus, Natick, MA) for
      metabolic research. In one protocol, saline delivery was measured in vitro in 5
      trials at 4 flow rates: 3, 30, 150, and 300 mL/h. In the second protocol, basal
      glycerol rate of appearance (Ra) was determined in vivo in 5 women on 2
      consecutive days. On day 1, [2-(13C)]glycerol was infused with 1 pump and
      [1,1,2,3,3-(2H5)]glycerol with the other. On day 2, the opposite pattern was
      used. The accuracy of the 2 pumps was the same (error approximately 2%). In
      addition, both the syringe and the peristaltic pumps were very precise, with
      coefficients of variation (CV) <1% at all flow rates. Glycerol Ra values were the
      same when tracer was infused with either a syringe or peristaltic pump on day 1
      and day 2: 4.1 +/- 1.7 (syringe pump) and 4.2 +/- 1.9 (peristaltic pump)
      micromol. kg fat mass (FM)(-1). min(-1) on day 1; 4.2 +/- 1.2 (syringe pump) and
      4.2 +/- 1.3 (peristaltic pump) micromol. kg FM(-1). min(-1) on day 2. These data
      demonstrate that both syringe and peristaltic pumps are very accurate and precise
      across a large range of flow rates. Moreover, the assessment of in vivo substrate
      kinetics in human subjects is the same when either pump is used to infuse isotope
      tracers.

PMID- 15254881
TI  - Relationships between serum soluble leptin receptor level and serum leptin and
      adiponectin levels, insulin resistance index, lipid profile, and leptin receptor
      gene polymorphisms in the Japanese population.
AB  - Leptin plays an important role in the regulation of body weight and is known to
      circulate in both free and bound forms. One of the leptin receptor isoforms
      exists in a circulating soluble form that can bind leptin. Clinical studies have
      shown that soluble leptin receptor (sOB-R) levels are lower in obese individuals.
      In the present study, we measured the serum sOB-R level in 419 healthy Japanese
      subjects (198 men and 221 women, aged 30 to 65 years, body mass index [BMI] 21.7
      +/- 2.6 [SD] kg/m2) and in 150 type 2 diabetic patients (96 men and 54 women, BMI
      24.3 +/- 3.8 kg/m2). We investigated the relationships between serum sOB-R level
      and BMI, blood pressure, homeostasis model assessment-insulin resistance index
      (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin
      receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. Serum leptin and sOB
      R levels were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent
      assay (ELISA), respectively. The serum sOB-R level in men was significantly
      higher than that in women. The serum sOB-R level was negatively correlated with
      BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated
      with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. The
      correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum
      leptin, adiponectin, and HDL-cholesterol levels were significant even after
      adjustment for age, sex, and BMI in healthy subjects. There was no association
      between serum sOB-R level and the LEPR polymorphisms examined. These findings
      suggest that the serum sOB-R level is negatively correlated with HOMA-IR and
      serum leptin level and positively correlated with HDL-cholesterol level and serum
      adiponectin level, independent of age, sex, and BMI, in the Japanese population.

PMID- 15254882
TI  - Free fatty acids increase hepatic glycogen content in obese males.
AB  - Obesity is associated with increased hepatic glycogen content. In vivo and in
      vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In
      this study we investigated the effect of physiological plasma FFA levels on
      hepatic glycogen metabolism by studying intrahepatic glucose pathways in lean and
      obese subjects. Six lean and 6 obese males were studied twice during a 16- to 22
      hour fast, once with and once without acipimox, an inhibitor of lipolysis.
      Intrahepatic glucose fluxes were measured by infusion of [2-(13C1)]glycerol, [1
      (2H1)]galactose, and [U-(13C6)]glucose. Acetaminophen was administered as a
      glucuronate probe. In both lean and obese control studies, plasma FFA levels
      increased progressively, whereas acipimox completely suppressed plasma FFA levels
      for the whole study period. In lean males glycogenolysis did not change in the
      acipimox study, but decreased in the control study (P < .01). In lean males,
      neither glycogen synthesis, glycogen synthesis retained as glycogen, nor glycogen
      balance differed between control and acipimox studies. In obese males
      glycogenolysis did not change in the acipimox study, but decreased in the control
      study (P < .01). Glycogen synthesis did not change in either study. Glycogen
      synthesis retained as glycogen did not change in acipimox study, but increased in
      the control study (P = .03). Glycogen balance did not change in the acipimox
      study, but increased in the control study (P < .01). This study demonstrates that
      in obese males physiological levels of FFA contribute to the retention of hepatic
      glycogen during short-term fasting by inhibiting breakdown of glycogen and
      increasing glycogen synthesis retained as glycogen, whereas in lean males this
      effect was absent due to unaltered glycogen synthesis retained as glycogen.

PMID- 15254883
TI  - Differences between nighttime and daytime hypoglycemia counterregulation in
      healthy humans.
AB  - Disturbances in hormonal counterregulation may be the main reason why many type 1
      diabetic patients are asymptomatic during nighttime hypoglycemia. While it is
      known that sleep attenuates counterregulatory responses to hypoglycemia, the
      influence of the time of day on hormonal counterregulation regulation remains
      obscure. We induced hypoglycemia at 2 different time intervals, ie, in the
      morning and in the early night, in healthy subjects staying awake throughout the
      experiments. As compared with the morning hypoglycemia, epinephrine response
      during early nighttime hypoglycemia was markedly enhanced (P < .001). Baseline
      corticotropin (ACTH) and cortisol levels were higher in the morning than during
      nighttime (P < .001 for both). However, the increase of both hormones was
      stronger at nighttime (P = .045 and P < .001, respectively), so that at the end
      of the hypoglycemic clamp, levels at nighttime were comparable to morning levels.
      In the morning, the increase in glucagon levels was more pronounced than during
      nighttime (P = .019), but given that baseline glucagon levels were distinctly
      higher at nighttime than in the morning (P = .003), at the end of the clamps,
      levels of this hormone remained still higher at nighttime than in the morning (P
      = .017). The increase in growth hormone during hypoglycemia did not differ
      between morning and nighttime (P = .728). Data shows that several components of
      hormonal counterregulation against hypoglycemia are influenced by the time of
      day. Especially, the markedly enhanced epinephrine response to early nighttime
      hypoglycemia could be clinically important, because this neuroendocrine response
      is known to play a crucial role in mediating the awareness of and metabolic
      defensive mechanism against hypoglycemia.

PMID- 15254884
TI  - Discrimination ratio analysis of inflammatory markers: implications for the study
      of inflammation in chronic disease.
AB  - To understand the role of inflammation in chronic disease it is important to have
      a reliable measure of habitual inflammatory status. A number of acute-phase
      response markers have been used as measures of inflammatory status, but the
      ability of a single measure to appropriately reflect habitual inflammatory status
      has not been assessed. This study compares the ability of different inflammatory
      markers to characterize habitual inflammatory status in overweight women. A
      single fasting blood sample was taken from 86 overweight women (mean body mass
      index [BMI], 35.2 kg/m2; range, 26.2 to 47.6 kg/m2) and a number of inflammatory
      markers (both acute-phase response markers and cytokines) were measured. A
      randomly selected subpopulation of 15 women attended on 2 further occasions for
      further blood samples. Using the subpopulation, discrimination ratios (DRs) were
      calculated for each inflammatory marker to assess the within-subject variability.
      The DRs were then used to determine the relationship between these markers,
      adjusted for within-subject variability, in the whole population. In this highly
      controlled experimental environment, interleukin-6 (IL-6), with a DR of 3.71, was
      the cytokine with the greatest ability to discriminate between subjects,
      suggesting that it is best able to characterize habitual inflammatory status.
      Sialic acid was the acute-phase response marker with the highest DR (3.16), and
      showed stronger correlations with other inflammatory markers, including C
      reactive protein (CRP), than IL-6. This study suggests that use of some
      inflammatory markers, such as CRP, with large within-individual variability, will
      underestimate the relationship between inflammation and disease, and thus
      relationships between inflammation and chronic disease may be stronger than
      previously appreciated. Future studies should consider IL-6 or sialic acid to
      provide a more robust measure of inflammatory status.

PMID- 15254885
TI  - Endogenous glucose production, insulin sensitivity, and insulin secretion in
      normal glucose-tolerant Pima Indians with low birth weight.
AB  - Individuals with low birth weight (LBW) are at increased risk of developing type
      2 diabetes in later life. Whether impairments in endogenous glucose production
      (EGP), insulin action, insulin secretion, or a combination thereof account for
      this association is unclear. We, therefore, examined these parameters in Pima
      Indians with normal glucose tolerance. Body composition, glucose and insulin
      responses during a 75-g oral glucose tolerance test (OGTT), EGP, insulin
      stimulated glucose disposal during low- and high-dose insulin infusion (M-low and
      M-high, hyperinsulinemic glucose clamp), and acute insulin response (AIR) to a 25
      g intravenous glucose challenge were measured in 230 Pima Indians (147 men and 83
      women, aged 25 +/- 0.4 years [mean +/- SE; range, 18 to 44]) with normal glucose
      tolerance. A subgroup of 63 subjects additionally underwent biopsies of
      subcutaneous adipose tissue for determination of adipocyte cell size and
      lipolysis. Subjects in the lowest quartile of birth weight (birth weight: 2,891
      +/- 33 g, LBW, n = 58) were compared to those whose birth weight was in the upper
      3 quartiles (birth weight: 3,657 +/- 28 g, NBW, n = 172). Age- and sex-adjusted
      body mass index (BMI), percent body fat, and waist-to-thigh ratio (WTR) were
      similar in LBW and NBW subjects. Suppression of EGP during the clamp was less in
      LBW than in NBW subjects before (P = .002) and after adjustment for age, sex,
      percent body fat, and M-low (P = .02). M-low and M-high were less in LBW than in
      NBW subjects before (P = .05 and P = .01) and after adjustment for age, sex,
      percent body fat, and WTR (P = .04 and P = .05). AIR was not different in LBW
      compared to NBW subjects before adjustments (P = .06), but it was lower in LBW
      than in NBW subjects after adjustment for age, sex, percent body fat, and M-low
      (P = .02), suggesting that AIR did not increase appropriately for the decrease in
      insulin-stimulated glucose disposal (M). In addition, average adipocyte cell size
      (P = .08) and basal lipolysis (P = .02) were higher in the LBW than in the NBW
      group. These results show that Pima Indians with LBW manifest a variety of
      impairments in metabolism in adulthood. Among these, a lesser insulin-stimulated
      suppression of EGP and a lesser insulin secretory capacity are the predominant
      ones. We conclude that interaction of multiple defects may contribute to
      increased susceptibility to type 2 diabetes among individuals with LBW.

PMID- 15254886
TI  - Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat
      fed rats.
AB  - High-fat feeding diminishes insulin-stimulated glucose transport in skeletal
      muscle. However, conflicting results are reported regarding whether
      phosphatidylinositol (PI)-3 kinase-independent glucose transport is also impaired
      in insulin-resistant high-fat-fed rodents. The aim of the present study was to
      study whether non-insulin-dependent mechanisms for stimulation of glucose
      transport are defective in skeletal muscle from high-fat-fed rats. Rats were fed
      normal chow diet or high-fat diet for 4 weeks and isolated epitrochlearis muscles
      were used for measuring glucose transport. Insulin-stimulated glucose transport
      was significantly lower in rats fed the high-fat diet compared with chow-fed rats
      (P < .05). Hypoxia-stimulated glucose transport was also reduced in high-fat-fed
      rats (P < .05). Nevertheless, hypoxia-stimulated adenosine monophosphate
      activated protein kinase (AMPK) phosphorylation (Thr172) level was not affected
      by high-fat feeding. Glucose transport by sodium nitroprusside stimulation was
      reduced in high-fat-fed rats (P < .05). Protein content of glucose transporter
      (GLUT)-4 and AMPK-alpha, and glycogen content were comparable between both
      groups. Our findings provide evidence that high-fat feeding can affect not only
      insulin but also non-insulin-stimulated glucose transport. A putative defect in
      common steps in glucose transport may play a role to account for impaired insulin
      stimulated glucose transport in rats fed a high-fat diet.

PMID- 15254887
TI  - Changes in bone mineral content after surgical treatment of morbid obesity.
AB  - Weight loss reduces bone mass and increases the risk of osteoporosis. This study
      was undertaken to assess changes of bone metabolism following Roux-en-Y gastric
      bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to
      nonoperated controls of morbidly obese subjects. Fourteen female and 5 male
      patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24
      month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation,
      and 6 patients were included in the control group. Bone metabolism was assessed
      by determination of serum parathyroid hormone (PTH), osteocalcin, urinary
      deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12,
      and 24 months after intervention. The body mass index (BMI) decreased from 41.0
      +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to
      30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the
      control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone
      mineral content (BMC) showed no significant change in the ASGB group (from 3,079
      +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940
      +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the
      RYGB group (P = .005). The loss in BMC was accompanied by significant increases
      in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after
      RYGB, suggesting both, increased bone resorption and increased bone formation.
      The authors were aware of the fact that the study groups were small and
      conclusions need to be regarded as preliminary. However, the RYGB operation
      resulted in enhanced weight loss and significant net loss of bone mass in
      comparison to ASGB and obese control subjects. Patients losing large amounts of
      body weight should be monitored regularly regarding prevention of osteoporosis.

PMID- 15254888
TI  - Increased serum soluble tumor necrosis factor receptor levels are associated with
      insulin resistance in liver cirrhosis.
AB  - Insulin resistance is present in nearly all patients with liver cirrhosis, but
      its etiology remains unclear. Recent studies have shown that tumor necrosis
      factor-alpha (TNF-alpha) system is involved in the insulin resistance of human
      obesity. Serum concentrations of TNF-alpha, and 2 soluble TNF receptors (sTNF-RI
      and sTNF-RII) are increased in cirrhotic patients. This study explored whether
      TNF-alpha system activity was associated with insulin resistance in liver
      cirrhosis. A total of 26 male nondiabetic patients with liver cirrhosis (mean
      age, 59 +/- 3 years; body mass index, 23.7 +/- 0.4 kg/m2) and 25 male control
      subjects (age, 65 +/- 2 years; body mass index, 24.4 +/- 0.5 kg/m2) were studied.
      Serum insulin, c-peptide, TNF-alpha, sTNF-RI, and sTNF-RII concentrations were
      determined by immunoassay. The insulin resistance was estimated by homeostasis
      assessment model (HOMA IR). In cirrhotic patients, serum levels of TNF-alpha,
      sTNF-RI, and sTNF-RII were all higher than those in the controls, and correlated
      with disease severity. Also, the serum c-peptide, insulin concentrations, and the
      HOMA IR were higher in liver cirrhosis with comparable blood glucose to control
      subjects, indicating a degree of insulin insensitivity. In the whole population,
      there was a moderate, but statistically significant, correlation between serum
      sTNF-RI or sTNF-RII, and HOMA IR. Also, body mass index was associated with HOMA
      IR, but not related to serum TNF-alpha, and sTNF-Rs levels. In multiple
      regression analysis, both sTNF-RII and body mass index jointly contributed to 30%
      variance of HOMA IR. Our study demonstrated that elevated sTNF-RII levels were
      associated with insulin resistance in liver cirrhosis. The data indicated that
      TNF-alpha system might play a role in modulating insulin action in patients with
      liver cirrhosis.

PMID- 15254889
TI  - Inhibition of ileal bile acid transport lowers plasma cholesterol levels by
      inactivating hepatic farnesoid X receptor and stimulating cholesterol 7 alpha
      hydroxylase.
AB  - We investigated the effect of SC-435, a competitive inhibitor of ileal apical
      sodium-dependent bile acid cotransporter (ASBT) on ileal bile acid absorption and
      the hepatic nuclear receptor FXR (farnesoid X receptor), which regulates
      cholesterol 7 alpha-hydroxylase (CYP7A1) activity and mRNA levels. Eighteen New
      Zealand White (NZW) rabbits were divided into 2 groups: controls (n = 10) and fed
      SC-435 125 mg/kg/d for 1 week (n = 8). In rabbits treated with SC-435, fecal bile
      acid outputs increased by more than 8 times, reflecting substantial bile acid
      malabsorption. Plasma cholesterol levels decreased 26%, while bile acid pool
      sizes and biliary bile acid outputs did not change after treatment. CYP7A1
      activity increased 64% and mRNA rose by 4 times after treatment. The expression
      of FXR target genes in the liver, short heterodimer partner (SHP) and bile salt
      export pump (BSEP), decreased 11.6 and 2.6 times, respectively, after treatment,
      which indicates inactivation of hepatic FXR. However, the mRNA levels of ileal
      bile acid binding protein (IBABP) did not change significantly, while ileal ASBT
      mRNA expression increased by 2.4 times after treatment. Rabbits treated with SC
      435 developed ileal bile acid malabsorption, which decreased the return of bile
      acids (FXR ligands) to the liver to inactivate hepatic FXR, which upregulated
      CYP7A1 and lowered plasma cholesterol levels. Although fecal bile acid
      malabsorption was substantial, increased bile acid production from hepatic
      cholesterol kept biliary bile acid outputs intact. Thus, a new balance was
      reached in the liver, where increased bile acid synthesis compensated for
      diminished ileal bile acid absorption to maintain the circulating enterohepatic
      bile acid pool.

PMID- 15254890
TI  - Effects of hyperglycemia, glucagon, and epinephrine on renal glucose release in
      the conscious dog.
AB  - The role of renal glucose production after an overnight fast and in response to
      different hormonal conditions has been debated. The aim of this study was to
      determine whether hyperglycemia, glucagon, or epinephrine can affect renal
      glucose production. In 18-hour fasted conscious dogs a pancreatic clamp initially
      fixed insulin and glucagon at basal levels, following which 1 of 4 protocols was
      instituted. In G+E glucagon (1.5 ng. kg(-1). min(-1); portally) and epinephrine
      (50 ng. kg(-1). min(-1); peripherally) were increased, in G glucagon was
      increased alone, in E epinephrine was increased alone, and in C neither were
      increased. In G, E, and C, glucose was infused to match the hyperglycemia in G+E
      (approximately 250 mg/dL). The average net renal glucose output during the last 2
      hours was not different from the basal values in any group. Furthermore, the
      changes in unidirectional renal glucose production were not significantly
      different among groups. Therefore, after an overnight fast in the conscious dog,
      the kidneys do not significantly contribute to overall glucose production or
      respond to glucagon or epinephrine.

PMID- 15254891
TI  - Combined intervention of soy isoflavone and moderate exercise prevents body fat
      elevation and bone loss in ovariectomized mice.
AB  - Body fat accumulation and bone loss are both often associated with estrogen
      deficiency following menopause. In this study, we examined whether soy
      isoflavone, one of the phytoestrogens, and moderate exercise interventions
      exhibit cooperative effects on body composition and bone mass in ovariectomized
      (OVX) mice. Eight-week-old female mice were assigned to 6 groups: (1) sham
      operated (sham); (2) OVX; (3) OVX with received a soy isoflavone diet (OVX+ISO);
      (4) OVX with exercised on a treadmill (OVX+EX); (5) OVX with given both
      isoflavone and exercise (OVX+ISO&EX ); and (6) OVX with treated with 17 beta
      estradiol subcutaneously (OVX+E2). Body composition and bone mineral density
      (BMD) were estimated by dual-energy x-ray absorptiometry (DXA). After the 6-week
      intervention, whole body fat (%) in the OVX group showed significantly higher
      than that in the sham group. Intervention of exercise and isoflavone alone
      partially inhibited OVX-induced body fat gain, and the combined intervention as
      well as E2 treatment completely restored fat mass to the sham level. Lean body
      mass in the whole body was not different in OVX group compared with that in
      OVX+ISO, OVX+EX, and OVX+E2 groups, but it was significantly higher in OVX+ISO&EX
      than in other groups. BMD of the whole body, lumbar spine, or femur showed
      significantly reduced by OVX, and the bone loss was partially inhibited by
      intervention of exercise or isoflavone alone. However, the combined intervention
      completely restored the bone mass to the level of sham, as did E2. Serum total
      cholesterol was significantly increased by OVX, which was normalized by the
      combined intervention or E2 treatment. These results demonstrate that combined
      intervention of soybean isoflavone and exercise prevented body fat accumulation
      in the whole body with an increase in lean body mass and restoration of bone
      mass, and reduced high serum cholesterol in OVX mice.

PMID- 15254892
TI  - Primacy of beta-cell dysfunction in the development of hyperglycemia: a study in
      the Japanese general population.
AB  - To elucidate the hierarchy in the evolution of glucose intolerance in the general
      population, the relationship between plasma glucose (PG), beta-cell function
      (insulinogenic index [II] = DeltaIRI(0-30)/DeltaPG(0-30) on 75 g oral glucose
      tolerance test [OGTT], where IRI is immunoreactive insulin), insulin sensitivity
      (Si; determined by quantitative insulin sensitivity check index [QUICKI]), age,
      and body mass index (BMI) were analyzed in 504 Japanese health examinees
      (men/women: 347/157). The mean (+/-SD) age was 53 (+/-11) years, BMI 23.6 (+/
      3.2) kg/m2, fasting PG (FPG) 5.61 (+/-0.97) mmol/L, 2-hour PG 7.42 (+/-3.1)
      mmol/L, II 74.2 (+/-169.3) [pmol/L]. [mmol/l](-1), and QUICKI 0.385 (+/-0.057)
      [log (microU/mL) + log (mg/100 mL)](-1). Higher FPG and 2-hour PG, respectively,
      were independently correlated with lower II, lower QUICKI, higher age, and higher
      BMI; the standardized correlation coefficient was largest for the correlation
      between PG and II. Based on the multiple linear regression, FPG = 8.565 - 1.201.
      log [II] - 5.374. QUICKI + 0.007. age + 0.030. BMI (r2 = 0.442), and 2-hour PG =
      14.239 - 4.206. log [II] - 0.141. QUICKI + 0.034 - age + 0.141. BMI (r2 = 0.493).
      Thus, elevation of PG correlated most prominently with beta-cell dysfunction and
      less prominently with decreased Si, higher age, and BMI (especially so in the
      case of 2-hour PG). In conclusion, the primacy of beta-cell dysfunction in the
      process of developing glucose intolerance was strongly suggested in the Japanese
      general population.

PMID- 15254894
TI  - Tissue interaction mediated by neuregulin-1 and ErbB receptors regulates
      epithelial morphogenesis of mouse embryonic submandibular gland.
AB  - Dimerization and activation of ErbB receptors by their ligands play crucial roles
      in organogenesis. Epithelial morphogenesis of embryonic mouse submandibular gland
      (SMG) has been shown to depend on intraepithelial signaling mediated by the
      epidermal growth factor (EGF) family of molecules and the EGF receptor (ErbB1).
      Here, we report on the neuregulin (NRG) -1 protein and its receptors ErbB2 and
      ErbB3 in the developing SMG. The expression of these molecules was demonstrated
      by reverse transcriptase-polymerase chain reaction and Western blot analysis.
      Immunofluorescence microscopy showed that the two ErbB receptors as well as ErbB1
      were expressed mainly in the epithelium, whereas NRG-1 was exclusively found in
      the mesenchyme. Epithelial morphogenesis was retarded by anti-NRG-1 neutralizing
      antibody and promoted by recombinant NRG-1 protein. We suggest that, in the
      developing SMG, both mesenchyme-derived NRG molecules and epithelium-derived EGF
      molecules regulate ErbB signaling in the epithelium to participate in tissue
      morphogenesis.

PMID- 15254895
TI  - cProx1 immunoreactivity distinguishes progenitor cells and predicts hair cell
      fate during avian hair cell regeneration.
AB  - In birds, mature sensory hair cells are regenerated continually in vestibular
      epithelia and after damage in the auditory basilar papilla. Molecular mechanisms
      governing the cellular processes associated with hair cell regeneration are
      poorly understood. Transcription factors are critical regulators of cell
      proliferation and differentiation in developing tissues. We examined
      immunoreactivity for cProx1 during both ongoing and damage-induced hair cell
      regeneration in chickens. Homologues of this divergent homeobox transcription
      factor are required for cell cycle withdrawal and differentiation in several
      vertebrate and invertebrate tissues. In the mitotically quiescent basilar
      papilla, a population of resting progenitor cells (supporting cells) shows faint
      nuclear immunoreactivity for cProx1. When auditory hair cell regeneration is
      triggered by experimental damage, nuclear cProx1 immunolabel is highly elevated
      in approximately 50% of dividing progenitor cells. Shortly after cytokinesis, all
      sibling pairs show symmetric patterns of nuclear cProx1 labeling, but pairs with
      asymmetric labeling emerge shortly thereafter. Strongly immunoreactive cells
      acquire the hair cell fate, whereas cells with low nuclear immunoreactivity
      differentiate as supporting cells. By contrast, cProx1 is not detected in any
      dividing progenitor cells during ongoing regeneration in the utricle. However,
      nuclear cProx1 immunoreactivity becomes asymmetric in postmitotic sibling cells,
      and as in the basilar papilla, cells with elevated cProx1 label differentiate as
      hair cells. In conclusion, cProx1 immunolabeling varies across sensory epithelial
      progenitors and distinguishes early differentiating hair cells from supporting
      cells. cProx1 may regulate the proliferative or differentiative capacities of
      progenitor cells and specify hair cell fate in postmitotic cells during avian
      hair cell regeneration.

PMID- 15254896
TI  - Early regeneration genes: Building a molecular profile for shared expression in
      cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.
AB  - Recent studies in Xenopus laevis have begun to compare gene expression during
      regeneration with that of the original development of specific structures (e.g.,
      the hindlimb and lens), while other studies have sought differences in gene
      expression between regeneration-competent and regeneration-incompetent stages. To
      determine whether there are any similarities between the regeneration of
      different structures, we have used a differential screen to seek shared early
      gene expression between hindlimb regeneration and cornea-lens
      transdifferentiation in the Xenopus tadpole. We have isolated 13 clones
      representing genes whose expression is up-regulated within the first few days of
      both regenerating processes and which are not demonstrably up-regulated in the
      context of basic wound healing. Furthermore, all of these genes also show
      prominent late embryonic expression. The expression patterns and putative
      identities of all 13 genes are presented, and a model is considered that allows
      us to characterize and profile important changes in gene expression, which might
      be shared among various regenerating and developmental systems.

PMID- 15254897
TI  - Cell contact-dependent mechanisms specify taste bud pattern during a critical
      period early in embryonic development.
AB  - After gastrulation, the pharyngeal endoderm is specified to give rise to taste
      receptor organs without further signaling from other embryonic tissues. We
      hypothesized that intercellular signaling might be responsible for the
      specification of taste buds. To test if and when this signaling was occurring,
      intercellular contacts were transiently disrupted in cultures of pharyngeal
      endoderm from axolotl embryos, and the number, size, and distribution of taste
      buds analyzed. Disruption of cell contacts at progressive time points, from
      neurula to late tail bud stages, revealed a critical period, during mid-tail bud
      stages, when disruption of cell contacts resulted in a significant increase in
      taste bud number and size. The spatial distribution of taste buds was also
      altered; taste buds were more clustered in explants disrupted during the critical
      period. These effects were not due to general alterations in mitosis and
      apoptosis. Rather, at least three aspects of taste bud patterning, i.e., number,
      size, and distribution, are governed by mechanisms dependent on normal cell
      contacts during a concise time window. Furthermore, our findings are consistent
      with specification of taste buds by means of lateral inhibitory signaling, which
      we hypothesize results from cell contact-dependent or short-range diffusible
      signals.

PMID- 15254898
TI  - Pax6 is a direct, positively regulated target of the circadian gene Clock.
AB  - Clock is a member of a highly conserved transcription control network that
      underlies the circadian cycle. During early embryogenesis, its expression is
      developmentally regulated and may be required for the normal development of the
      head. In this report, the transcription factor Pax6, a highly conserved regulator
      of anterior development, is shown to be a direct target of Clock regulation.

PMID- 15254899
TI  - Regulation of expression of mouse interferon-induced transmembrane protein like
      gene-3, Ifitm3 (mil-1, fragilis), in germ cells.
AB  - Mouse interferon-induced transmembrane protein (IFITM) gene, Ifitm3 (previously
      known as mil-1 and fragilis), is expressed in primordial germ cells (PGCs), in
      their precursors, and in germ cells of the fetal gonads (Saitou et al. [2002]
      Nature 418:293-300; Tanaka and Matsui [2002] Mech Dev 119S:S261-S267). By
      examining the expression of green fluorescent protein transgene under the control
      of DNA sequences flanking exon 1, we have identified domains that direct Ifitm3
      transcription in PGCs and their precursors in gastrula stage and 13.5 days post
      coitum embryos. Germ cell-specific expression is achieved by the activity of a
      consensus element unique to the Ifitm genes, which may act to suppress Ifitm3
      expression in somatic tissues. The lack of any influence of the interferon
      stimulable response elements on transgene expression in the germ-line suggests
      that interferon-mediated response is not critical for activating Ifitm3.

PMID- 15254900
TI  - Identification of tyrosine kinases expressed in the male mouse gubernaculum
      during development.
AB  - The gubernaculum is a mesenchymal tissue that connects the gonads to the inguinal
      abdominal wall in the mammalian embryo. During gestation in the male,
      differential development of the gubernaculum and regression of the cranial
      suspensory ligament coordinate the first phase of testicular descent. As many as
      1-3% newborn boys show impaired testicular descent, in part due to problems in
      gubernacular development. Little is known about the signaling molecules and
      cascades that are required for the development and differentiation of the
      gubernaculum. Protein tyrosine kinases comprise a large class of proteins that
      play important roles in proliferation, differentiation, and many aspects of cell
      cell signaling in tissues. To date, no information on the existence of members of
      tyrosine kinase family in gubernaculum is available. We used a reverse
      transcription-polymerase chain reaction approach to identify 25 individual
      members of cytoplasmic and receptor tyrosine kinase classes in the developing
      male gubernaculum. The analysis of cellular distribution suggests that each
      tyrosine kinase examined may play a unique role in gubernacular development and
      differentiation.

PMID- 15254901
TI  - Critical role for retinol in the generation/differentiation of angioblasts
      required for embryonic blood vessel formation.
AB  - Numerous studies demonstrate that vitamin A (retinol) deficiency causes abnormal
      cardiovascular morphogenesis. We evaluated the impact of retinol deficiency on
      the regulation of the numbers of endothelial cells and angioblasts (endothelial
      progenitors) produced during embryonic quail development. At the one-somite
      stage, there were no discernible differences in the mean number of endothelial
      cells or angioblasts in normal and retinol-deficient embryos. However, retinol
      deficient embryos at the three-somite stage had an increase in the mean number of
      endothelial cells but no difference in the mean number of angioblasts. By
      contrast, retinol-deficient embryos at the five-somite stage have 61% of the
      normal number of endothelial cells and 12% of the normal number of angioblasts.
      Similarly, retinol-deficient embryos at the 10-somite stage had 71% and 60% of
      normal numbers of endothelial cells in capillary-like networks and the sinuses
      venosus, respectively. Furthermore, we show that retinol deficiency did not
      elicit a global reduction in mesodermal cell numbers but was specific to cells of
      the endothelial lineage. Taken together, our findings suggest that vascular
      abnormalities observed under conditions of retinol deficiency are due to
      reduction in the number of angioblasts and consequently an insufficiency in the
      number of endothelial cells required to build complex vascular networks.

PMID- 15254902
TI  - Polysialic acid regulates cell contact-dependent neuronal differentiation of
      progenitor cells from the subventricular zone.
AB  - Expression of polysialic acid (PSA) promotes migration of progenitor cells from
      the subventricular zone (SVZ) to the olfactory bulb, where they differentiate
      into interneurons. This differentiation has been found to coincide with a loss of
      PSA. Moreover, specific removal of PSA from the mouse SVZ by endoneuraminidase-N
      was found to cause premature differentiation, as evidenced by neurite outgrowth
      and tyrosine hydroxylase synthesis in vivo and by expression of neurofilament-L
      and beta III-tubulin in SVZ explant cultures. This differentiation involved
      activation of mitogen-activated protein kinase through p59fyn and was blocked by
      its inhibition. The effects of PSA removal were found to be cell contact
      dependent and to be reduced by anti-neural cell adhesion molecule antibodies.
      These findings indicate that PSA expression regulates the fate of SVZ precursors
      by two contact-dependent mechanisms, the previously reported reduction in cell
      cell adhesion that allows cell translocation, and the postponement of cell
      differentiation that otherwise would be induced by signals generated through
      surface molecule-mediated cell-cell interactions.

PMID- 15254903
TI  - Unique and redundant roles of Smad3 in TGF-beta-mediated regulation of long bone
      development in organ culture.
AB  - The most well-characterized intracellular signaling molecules for transforming
      growth factor-beta (TGF-beta) are the Smads. R-Smads interact with and are
      phosphorylated directly by the TGF-beta type I receptor. Phosphorylated R-Smads
      can then associate with Smad4, translocate to the nucleus and regulate
      transcription. Specific R-Smads transduce distinct signals for members of the TGF
      beta superfamily. Smad2 and -3 mediate signaling by TGF-beta/activin, whereas
      Smad1, -5, and -8 mediate bone morphogenetic protein signaling. TGF-beta inhibits
      proliferation and hypertrophic differentiation in metatarsal organ cultures by a
      perichondrium-dependent mechanism. To determine the mechanism of TGF-beta
      signaling in the perichondrium, we tested the hypothesis that TGF-beta-restricted
      Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in
      embryonic metatarsal organ cultures. Perichondrium was infected with adenoviruses
      containing dominant-negative forms of Smad2 (Ad-Smad2-3SA) and Smad3 (Ad-Smad3
      Delta C). Proliferation and differentiation were measured in response to
      treatment with TGF-beta 1. Results were compared with control bones infected with
      a beta-galactosidase reporter virus (Ad-beta-gal). Infection with Ad-Smad2-3SA
      completely blocked the effects of TGF-beta 1 on metatarsal development while Ad
      Smad3 Delta C only partially blocked TGF-beta 1 effects. To further characterize
      the role of Smad3 in long bone development, TGF-beta 1 responsiveness in cultures
      from Smad3(+/+) and Smad3(ex8/ex8) mice were compared. Loss of Smad3 only
      partially blocked the effects of TGF-beta1 on differentiation. In contrast, the
      effects of TGF-beta 1 on chondrocyte proliferation were blocked completely. We
      conclude that Smad2 signaling in the perichondrium can compensate for the loss of
      Smad3 to regulate inhibition of hypertrophic differentiation; however, Smad3 is
      required for TGF-beta 1-mediated effects on proliferation.

PMID- 15254904
TI  - Expression patterns of Xenopus FGF receptor-like 1/nou-darake in early Xenopus
      development resemble those of planarian nou-darake and Xenopus FGF8.
AB  - Fibroblast growth factors (FGFs) mediate many cell-to-cell signaling events
      during early development. Nou-darake (ndk), a gene encoding an FGF receptor
      (FGFR)-like molecule, was found to be highly and specifically expressed in the
      head region of the planarian Dugesia japonica, and its functional analyses
      provided strong molecular evidence for the existence of a brain-inducing circuit
      based on the FGF signaling pathway. To analyze the role of ndk during vertebrate
      development, we isolated the Xenopus ortholog of ndk, the vertebrate FGFR-like 1
      gene (XFGFRL1). Expression of XFGFRL1/Xndk was first detected in the anterior
      region at the late gastrula stage and dramatically increased at the early neurula
      stage in an overall anterior mesendodermal region, including the prechordal
      plate, paraxial mesoderm, anterior endoderm, and archenteron roof. This anterior
      expression pattern resembles that of ndk in planarians, suggesting that the
      expression of FGFRL1/ndk is conserved in evolution between these two distantly
      diverged organisms. During the tail bud stages, XFGFRL1/Xndk expression was
      detected in multiple regions, including the forebrain, eyes, midbrain-hindbrain
      boundary, otic vesicles, visceral arches, and somites. In many of these regions,
      XFGFRL1/Xndk was coexpressed with XFGF8, indicating that XFGFRL1/Xndk is a member
      of the XFGF8 synexpression group, which includes sprouty, sef, and isthmin.

PMID- 15254906
TI  - Cellular expression of eve1 suggests its requirement for the differentiation of
      the ameloblasts and for the initiation and morphogenesis of the first tooth in
      the zebrafish (Danio rerio).
AB  - even-skipped-related (evx) genes encode homeodomain-containing transcription
      factors that are involved in a series of developmental processes such as
      posterior body patterning and neurodifferentiation. Although evx1 and evx2 were
      not reported to be expressed during mammalian tooth development, we present here
      evidence that eve1, the closest paralog of evx1 in the actinopterygian lineage,
      is expressed during pharyngeal tooth formation in the zebrafish, Danio rerio. We
      have performed whole-mount in situ hybridization on zebrafish embryos and larvae
      ranging from 24 to 192 hours postfertilization (hpf). A detailed analysis of
      serial sections through the pharyngeal region of whole-mount hybridized and
      control specimens indicates that only dental epithelial cells express eve1. eve1
      transcription was activated at 48 hpf, in the placode of the first tooth (i.e.,
      the initiation site of tooth 4V(1)), and maintained in the dental epithelium
      throughout morphogenesis. Then, by 72 hpf, eve1 expression was restricted to the
      differentiating ameloblasts of the enamel organ during early differentiation
      stage, and this expression decreased as soon as matrix was deposited. In
      subsequent primary teeth (3 V(1) and 5 V(1)) as well as in their successors
      (replacement teeth 4V(2), 3V(2), and 5V(2)), eve1 expression was restricted to
      the differentiating ameloblasts and, again, disappeared when matrix was
      deposited. Therefore, in the zebrafish, eve1 expression in the pharyngeal region
      is correlated with two key steps of tooth development: initiation and
      morphogenesis of the first tooth, and ameloblast differentiation of all
      developing teeth.

PMID- 15254905
TI  - Cellular localization and signaling activity of beta-catenin in migrating neural
      crest cells.
AB  - In the vertebrate embryo, development of the neural crest is accompanied by
      sequential changes in cellular adhesiveness, allowing cells to delaminate from
      the neural epithelium, to undergo migration through extracellular matrix
      material, and to coalesce into ganglia of the peripheral nervous system. Because
      of its dual role in cell adhesion, as a link between cadherins and the actin
      cytoskeleton, and in cell signaling, as a key mediator of the Wnt-signaling
      pathway, beta-catenin is a good candidate to play a central role in the control
      of neural crest cell development. In the present study, we analyzed, by using an
      in vitro culture system, whether the cellular localization and the signaling
      activity of beta-catenin are regulated in conjunction with cell migration during
      ontogeny of trunk neural crest cells in the avian embryo. beta-Catenin molecules
      were found primarily in association with N-cadherin in the regions of
      intercellular contacts in most migrating neural crest cells, and only early
      migrating cells situated in proximity with the dorsal side of the neural tube
      showed detectable beta-catenin in their nuclei. This finding indicates that beta
      catenin may be recruited for signaling in neural crest cells only transiently at
      the onset of migration and that sustained beta-catenin signals are not necessary
      for the progression of migration. The nuclear distribution of beta-catenin within
      crest cells was not affected upon modification of the N-cadherin-mediated cell
      cell contacts, revealing that recruitment of beta-catenin for signaling is not
      driven by changes in intercellular cohesion during migration. Overstimulation of
      beta-catenin signals in neural crest cells at the time of their migration, using
      LiCl treatment or coculture with Wnt-1-producing cells, induced nuclear
      translocation of beta-catenin and Lef-1 up-regulation in neural crest cells and
      provoked a marked inhibition of cell delamination and migration. The effect of
      LiCl and exogenous Wnt-1 on neural crest cells could be essentially attributed to
      a dramatic decrease in integrin-mediated cell-matrix adhesion as well as a
      massive reduction of cell proliferation. In addition, although it apparently did
      not affect expression of neural crest markers, Wnt-1 exposure dramatically
      affected signaling events involving Notch-Delta, presumably also accounting for
      the strong reduction in cell delamination. In conclusion, our data indicate that
      beta-catenin functions primarily in cell adhesion events during migration and may
      be recruited transiently for signaling during delamination possibly to regulate
      the balance between cell proliferation and cell differentiation.

PMID- 15254907
TI  - Functional conserved elements mediate intestinal-type fatty acid binding protein
      (I-FABP) expression in the gut epithelia of zebrafish larvae.
AB  - Intestinal-type fatty acid binding protein (I-FABP) plays an important role in
      the intracellular binding and trafficking of long chain fatty acids in the
      intestine. The aim of this study, therefore, was to elucidate the regulation and
      spatiotemporal expression of the I-FABP gene during zebrafish larval development.
      We performed in vivo reporter-gene analysis in zebrafish by using a transient and
      transgenic approach. Green fluorescent protein-reporter analyses revealed that
      the proximal 192-bp region of the I-FABP promoter is sufficient to direct
      intestine-specific expression during zebrafish larval development. Functional
      dissection of a 41-bp region within this 192-bp promoter revealed that one C/EBP
      and two GATA-like binding sites, along with a novel 15-bp element within it are
      required for I-FABP gene expression in vivo. In addition, the six consensus sites
      (CCACATCAGCATGAA) in the 15-bp element are critical for I-FABP gene regulation in
      the zebrafish gut epithelia. Comparison analyses of the orthologous 15-bp element
      from mammalian I-FABP genes suggests that these mammalian elements are
      functionally equivalent to the zebrafish 15 element. These results provide the
      first in vivo evidence that these binding sites (C/EBP and GATA) and the novel 15
      bp element contribute to intestine-specific gene expression and that they are
      functionally conserved across vertebrate evolution.

PMID- 15254908
TI  - T-box genes in the ascidian Ciona intestinalis: characterization of cDNAs and
      spatial expression.
AB  - Members of the T-box family of transcription factors share an evolutionarily
      conserved DNA-binding domain and play significant roles in various processes of
      embryonic development. Vertebrate T-box genes are categorized into the following
      five major subfamilies (eight groups), depending on sequence similarities:
      Brachyury, Tbx1 (Tbx1/10, Tbx15/18/22, Tbx20), Tbx2/3/4/5 (Tbx2/3 and Tbx4/5),
      Tbx6, and Tbr/Eomes/TBX21. Ascidians are primitive chordates, and their tadpole
      larva are considered to represent the simplified and basic body plan of
      vertebrates. In addition, it has been revealed that the ascidian genome contains
      the basic ancestral complement of genes involved in development. The present
      characterization of cDNAs and survey of the Ciona intestinalis draft genome
      demonstrated that the Ciona genome contains a single copy gene for each of the
      Brachyury, Tbx1/10, Tbx15/18/22, Tbx20, Tbx2/3, and Tbr/Eomes/TBX21 groups, and
      at least three copies of the Tbx6 subfamily. Each of the Ciona T-box genes shows
      a characteristic expression pattern, although that of Tbx20 was not determined in
      the present study. These results provide basic information that will be useful
      for future studies of the function of each gene, genetic cascades of different T
      box genes, and genome-wide surveys of evolutionary changes in the T-box gene
      structure and organization in this primitive chordate.

PMID- 15254909
TI  - Retinoic acid receptor alpha is required for synchronization of spermatogenic
      cycles and its absence results in progressive breakdown of the spermatogenic
      process.
AB  - Targeted mutagenesis of the retinoic acid receptor alpha (RAR alpha) gene has
      revealed its essential role in spermatogenesis. Although cells in all stages of
      spermatogenesis were detected in RAR alpha(-/-) testes, there was an increase in
      degenerating pachytene spermatocytes and a temporary developmental arrest in step
      8-9 spermatids in the first wave of spermatogenesis, a delay in the onset of the
      second wave, and a temporary arrest in preleptotene to leptotene spermatocytes in
      the first, second, and third waves. A striking aspect of the mutant phenotype was
      the failure of spermatids to align at the tubular lumen at stage VIII.
      Furthermore, there were missing or decreased numbers of the predicted cell types
      in tubules, and they exhibited a profound asynchrony of mixed spermatogenic cell
      types. In vivo bromodeoxyuridine labeling revealed a significant decrease in germ
      cell proliferation in both juvenile and adult RAR alpha(-/-) testes and confirmed
      the arrest at step 8-9 spermatids. Retinoid signaling through RAR alpha, thus,
      appears to be critical for establishment of synchronous progression of
      spermatogenesis and the subsequent establishment of correct cellular
      associations.

PMID- 15254910
TI  - Neurotrophin-3 and TrkC are expressed in the outflow tract of the developing
      chicken heart.
AB  - Transcripts encoding trkC and full-length (catalytic) TrkC receptors were
      detected in the outflow tract of the chicken heart during early development
      (stage 17; embryonic day [E] 2.5) before the start of septation. Expression of
      trkC mRNA persisted through early septation (stage 25, E4.5-E5) but was no longer
      evident by the end of septation (stage 34, E8). Neurotrophin-3 (NT-3) mRNA was
      also shown to be present in the outflow tract throughout cardiac development.
      Quail-chick chimeras were used to confirm that cardiac neural crest cells were
      not present in the outflow tract at stage 17 (E2.5). Our results show that NT-3
      interacts with cells in the outflow tract that are not of neural crest origin.
      This finding indicates that, in addition to effects on neural crest cells, NT-3
      may be important for cardiac development due to its interaction with cells in the
      outflow tract such as those arising from the secondary heart field.

PMID- 15254911
TI  - MAP kinase activation in avian cardiovascular development.
AB  - Signaling pathways mediated by receptor tyrosine kinases (RTK) and mitogen
      activated protein kinase (MAPK) activation have multiple functions in the
      developing cardiovascular system. The localization of diphosphorylated
      extracellular signal regulated kinase (dp-ERK) was monitored as an indicator of
      MAPK activation in the forming heart and vasculature of avian embryos. Sustained
      dp-ERK expression was observed in vascular endothelial cells of embryonic and
      extraembryonic origins. Although dp-ERK was not detected during early cardiac
      lineage induction, MAPK activation was observed in the epicardial, endocardial,
      and myocardial compartments during heart chamber formation. Endocardial
      expression of dp-ERK in the valve primordia and heart chambers may reflect
      differential cell growth associated with RTK signaling in the heart. dp-ERK
      localization in the epicardium, subepicardial fibroblasts, myocardial
      fibroblasts, and coronary vessels is consistent with MAPK activation in
      epicardial-derived cell lineages. The complex temporal-spatial regulation of dp
      ERK in the heart supports diverse regulatory functions for RTK signaling in
      different cell populations, including the endocardium, myocardium, and epicardial
      derived cells during cardiac organogenesis.

PMID- 15254912
TI  - Expression of zebrafish six1 during sensory organ development and myogenesis.
AB  - Drosophila sine oculis homologous genes in vertebrates are homeobox-containing
      transcription factors functioning within the Pax-Six-Eya-Dach regulatory network
      during development. In this study, we describe the cloning and expression of a
      zebrafish homolog of sine oculis, six1. The reverse transcription-polymerase
      chain reaction demonstrated accumulation of six1 transcripts at mid-gastrula, and
      in situ hybridization showed their subsequent expression in the cranial placode
      and later in the olfactory, otic, and lateral line placodes, inner ear, and
      neuromasts. In addition, six1 is expressed in the pituitary, branchial arches,
      somites, pectoral fin, ventral abdomen muscle, and the cranial muscles of the eye
      and lower jaw. An increase of six1 expression was observed in the lateral line,
      muscles, and inner ear of the mind bomb mutant, illustrating a regulatory effect
      of the Notch pathway on expression of Six genes.

PMID- 15254913
TI  - Organization of fibroblasts in the heart.
AB  - Cardiac fibroblasts are organized into a three-dimensional network in the heart.
      This organization follows the endomysial weave network that surrounds groups of
      myocytes. Reverse transcriptase-polymerase chain reaction, Western blots, and
      immunohistochemistry were used to show that discoidin domain receptor 2 (DDR2)
      was specific for cardiac fibroblasts and not expressed on endothelial cells,
      smooth muscle cells, or cardiac myocytes. DDR2 is expressed early in development
      and in the adult heart. High voltage electron microscopy (HVEM), scanning
      electron microscopy, and laser scanning confocal microscopy document the three
      dimensional organization of fibroblasts in the heart. Antibodies against connexin
      43 and 45 showed different patterns but confirmed, along with HVEM, that
      fibroblasts are connected to each other as well as cardiac myocytes. The
      implications of this arrangement of fibroblasts can be important to cardiac
      function. The signaling of DDR2 and the expression of matrix metalloproteinase 2
      in relation to collagen turnover and remodeling is discussed.

PMID- 15254914
TI  - Presenilin 1 is essential for cardiac morphogenesis.
AB  - Presenilin 1 (PS1) is the gene responsible for the development of early-onset
      familial Alzheimer's disease. PS1-deficient mice have been reported to show
      defects in neurogenesis, somitogenesis and angiogenesis. Here, we report cardiac
      anomaly in PS1-deficient mice: the mutant hearts exhibited ventricular septal
      defect, double outlet right ventricle, and stenosis in the pulmonary artery.
      Immunohistochemistry using anti-PS1 antibody revealed the prominent expression of
      PS1 in mesenchymal cells at the septal area of the wild-type heart. These results
      suggest that PS1 may play an essential role in heart development.

PMID- 15254915
TI  - Neuroglian stabilizes epithelial structure during Drosophila oogenesis.
AB  - The vertebrate L1 family of cell adhesion molecules (CAMs) and their fly homolog,
      Neuroglian, are members of the immunoglobulin (Ig) superfamily of CAMs. In
      general, Ig CAMs have been found to play critical roles in mediating axon
      guidance. One Ig CAM, NCAM, has also been implicated in maintaining epithelial
      integrity and suppressing metastatic dissemination of tumor cells. Other Ig CAMs,
      such as Nrg, are also expressed in epithelia. We thus tested the hypothesis that,
      like NCAM, Nrg might also be required for maintaining epithelial integrity and
      for inhibiting tumor invasion. We used the Drosophila follicular epithelium to
      determine the function of Nrg in vivo in maintaining epithelial structure, and in
      regulating the motility of migrating border cells and invasive tumorous follicle
      cells. Nrg(167) is expressed on the lateral membrane of follicle cells. Loss of
      Nrg(167) causes border cells to delay delamination and causes other follicle
      cells to delaminate inappropriately. The delaminated cells have aberrant
      epithelial polarity manifested as severe mislocalization of apical and basal
      membrane proteins, and uniform localization of lateral membrane proteins.
      Furthermore, loss of Nrg(167) dramatically enhances the invasive phenotype
      associated with loss of Discs Large, a neoplastic tumor suppressor. These results
      indicate that Nrg(167) stabilizes epithelial polarity by regulating junctional
      adhesion and function in normal and tumorous epithelia. Our data also suggest
      that Ig superfamily members have significant functional redundancy in maintaining
      epithelial polarity, with individual members playing subtle, unique roles during
      epithelial morphogenesis.

PMID- 15254917
TI  - Psychosocial correlates of late-onset psychosis: life experiences, cognitive
      schemas, and attitudes to ageing.
AB  - BACKGROUND: Psychosis with first onset after the age of 60, and arising in the
      absence of dementia or primary affective disorder, is thought to affect 2-4% of
      older people, and as many as half will not respond fully to medication. AIMS:
      This study represents a preliminary attempt to explore a number of possible
      psychosocial correlates of late-onset psychosis with potential relevance for a
      cognitive-behavioural formulation and for the development of psychosocial
      interventions for this group. METHODS: The nature and extent of adverse early
      life experiences, presence of maladaptive cognitive schemas, and morale in
      relation to ageing were compared for older people with a diagnosis of late-onset
      psychosis (LOP; n = 14) or late-onset depression (DEP; n = 13) and healthy older
      volunteers (HEV; n = 18) in a cross-sectional design. RESULTS: Both LOP and DEP
      groups reported significantly higher levels of adverse life experiences than the
      HEV group, with between-group differences in the types of experiences described.
      The LOP group scored significantly higher than the HEV group on four out of five
      schema domains, and significantly higher than the DEP group on two domains, other
      directedness and over-vigilance/inhibition. The LOP group had significantly lower
      overall morale in relation to ageing than the HEV group, reflecting significantly
      higher levels of lonely-dissatisfaction. CONCLUSIONS: Life experiences, cognitive
      schemas and attitudes to ageing are important psychosocial correlates of LOP.
      These findings contribute to an understanding of the emotional world of
      individuals who develop psychosis in later life and may have implications for
      developing more effective intervention approaches.

PMID- 15254918
TI  - Donepezil for the symptomatic treatment of patients with mild to moderate
      Alzheimer's disease: a meta-analysis of individual patient data from randomised
      controlled trials.
AB  - BACKGROUND: The objective was to evaluate the efficacy and tolerability of
      donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations
      of mild to moderate Alzheimer's disease (AD). METHOD: A systematic review of
      individual patient data from Phase II and III double-blind, randomised, placebo
      controlled studies of up to 24 weeks and completed by 20 December 1999. The main
      outcome measures were the ADAS-cog, the CIBIC-plus, and reports of adverse
      events. RESULTS: A total of 2376 patients from ten trials were randomised to
      either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893).
      Cognitive performance was better in patients receiving donepezil than in patients
      receiving placebo. At 12 weeks the differences in ADAS-cog scores were 5 mg/day
      placebo: - 2.1 [95% confidence interval (CI), - 2.6 to - 1.6; p < 0.001], 10
      mg/day-placebo: - 2.5 ( - 3.1 to - 2.0; p < 0.001). The corresponding results at
      24 weeks were - 2.0 ( - 2.7 to - 1.3; p < 0.001) and - 3.1 ( - 3.9 to - 2.4; p <
      0.001). The difference between the 5 and 10 mg/day doses was significant at 24
      weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC-plus at 12
      weeks were: 5 mg/day-placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day-placebo 1.9
      (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to
      2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated;
      adverse events were cholinergic in nature and generally of mild severity and
      brief in duration. CONCLUSION: Donepezil (5 and 10 mg/day) provides meaningful
      benefits in alleviating deficits in cognitive and clinician-rated global function
      in AD patients relative to placebo. Increased improvements in cognition were
      indicated for the higher dose.

PMID- 15254919
TI  - Risk indicators of depression in residential homes.
AB  - OBJECTIVES: To assess risk indicators of depressive symptoms in social and
      personal domains of residents of residential homes. METHODS: In a cross-sectional
      study risk indicators for depressive symptoms (Geriatric Depression Scale) were
      examined in bivariate and multivariate analyses, four hundred and seventy-nine
      elderly subjects from 11 residential homes took part in the study. RESULTS:
      Functional impairment, loneliness, higher education levels, a family history of
      depression and neuroticism are associated with depressive symptom. CONCLUSION:
      The risk indicators of depression found in residential homes are similar to those
      in the community.

PMID- 15254920
TI  - Delirium in elderly hospitalised patients: protective effects of chronic
      rivastigmine usage.
AB  - OBJECTIVES: To investigate the efficacy of the chronic usage of the
      cholinesterase inhibitor rivastigmine in patients with dementia in the prevention
      of delirium in case of hospitalisation. DESIGN: Retrospective cohort study.
      SETTING: Non-geriatric wards of an 1120 bed general teaching hospital in s
      Hertogenbosch, The Netherlands. PARTICIPANTS: Of a group of 366 hospitalised
      patients, treated by the geriatric consultation team from January 2002 until June
      2003, the patients who used rivastigmine chronically were compared with a
      randomly selected subgroup of all patients not treated with rivastigmine.
      MEASUREMENTS: The occurrence and duration of a delirium, co-morbidity, use of
      medication, length of hospitalisation and psychosocial data were collected from
      the medical charts of the geriatric consultation team. RESULTS: 11 patients (3%)
      were chronic rivastigmine users. A control group of 29 subjects was randomly
      selected from the non-rivastigmine users of the patient population. In the group
      that used rivastigmine five patients (45.5%) developed a delirium, compared with
      8 (88.9%) in the control group (p < 0.05). CONCLUSIONS: Chronic rivastigmine use
      may contribute to the prevention of a delirium in a high-risk group of elderly
      hospitalised patients suffering from dementia.

PMID- 15254921
TI  - Competence to consent to treatment of geriatric patients: judgements of
      physicians, family members and the vignette method.
AB  - OBJECTIVE: In absence of a gold standard of methods to assess competence, three
      judgements of competency of geriatric patients are evaluated: the judgements of a
      physician, the judgement of a family member, and the judgement of an instrument.
      METHODS: Competence of 80 geriatric patients was judged both by a physician and a
      family member. Decision making capacity was assessed with a vignette. A vignette
      describes a treatment choice, after which the following abilities are evaluated:
      evidencing a choice, understanding, reasoning and appreciating a situation.
      Cognitive functioning was measured with the Mini-Mental State Examination.
      RESULTS: Most of the geriatric patients were judged competent by all three
      methods. Disagreement between the three judgements was found for 25 patients.
      Agreement about incompetence was only reached for one patient. Physicians
      appeared to be most lenient in their incompetency judgement: only three patients
      were judged incompetent. These patients scored significantly lower than competent
      patients on cognitive functioning, the decisional ability of understanding, and
      the total vignette score. Family members appeared to be most stringent in their
      judgement: they considered 22 patients incompetent. Incompetent patients scored
      significantly lower than competent patients on cognitive functioning, reasoning
      and the total vignette score. CONCLUSIONS: The disagreement between the
      judgements suggests a difference in factors given emphasis by the three methods.
      The finding that both the judgement of physicians and family members are
      associated with the assessment of the vignette, suggests that the vignette method
      has more than a legal theoretical base and is associated with daily life
      experience and knowledge as well. Physicians can be helped to assess competence
      by the vignette method to evaluate decisional abilities and by family members who
      can provide more information about patients' values.

PMID- 15254922
TI  - Depression in frail elders: impact on family caregivers.
AB  - OBJECTIVES: To examine the relationship between depression among medically ill,
      frail elders and family caregivers' hours of care, health status, and quality of
      life. DESIGN AND METHODS: A cross-sectional study of 193 family caregivers of
      seniors treated in the emergency department (ED) was conducted. Measures included
      patient depression (Geriatric Depression Scale-15), and caregivers' hours of
      care, mental health and physical functioning (SF-36), and quality of life (EQ
      5D). RESULTS: Mean caregiver age was 60.0 +/- 16.1 years and 70.5% were female.
      More caregivers of depressed seniors provided more care in the previous month
      (37.3% vs 22.4%, p = 0.03), had poor mental health (63.5% vs 47.0%, p = 0.03),
      and poor perceived quality of life (63.5% vs 50.4%, p = 0.04) compared to
      caregivers of non-depressed seniors. Multiple logistic regression analyses
      indicated that patient depression was associated with poor caregiver quality of
      life (OR = 3.15, 95% CI 1.48, 6.73), and poor mental health in spousal and adult
      child caregivers (OR = 2.72, 95% CI = 0.88, 8.39, and OR = 3.29, 95% CI = 1.10,
      9.86, respectively). CONCLUSIONS: Psychosocial support may be needed for
      caregivers of depressed seniors.

PMID- 15254923
TI  - Plasma homocysteine concentration relates to the severity but not to the duration
      of Alzheimer's disease.
AB  - BACKGROUND: It has been reported that plasma tHcy concentration is elevated in
      patients with Alzheimer's disease (AD) and relates to the progress or the
      development of AD. In the present study we have compared plasma tHcy
      concentrations at different times during the course of AD and with measures
      corresponding to the severity and the progress rate of AD. METHODS: The study
      population consisted of 159 patients with AD. Three measures corresponding to the
      progress rate of AD were created by dividing the actual scores of the severity of
      the dementia, the Berger scale and the Katz index by the estimated duration.
      RESULTS: AD patients without a history of cardiovascular disease did not show a
      significant increase of plasma tHcy concentration compared to the control
      subjects, whereas AD patients with cardiovascular disease exhibited a significant
      increase of plasma tHcy concentration compared to both control subjects and
      patients without cardiovascular disease. However, after creatinine adjustment of
      plasma tHcy in control subjects and AD patients a significant increase of plasma
      tHcy was observed also in AD patients without cardiovascular disease compared to
      controls. The concentration of plasma tHcy in AD patients with and without
      cardiovascular history did not increase with time after disease onset. Plasma
      tHcy concentration correlated with the severity of the disease. The correlations
      between plasma tHcy and measures of rate progression of AD did not improve
      compared with the correlations between plasma tHcy and the severity of dementia.
      CONCLUSION: An interpretation of these findings may be that plasma tHcy is
      additionally increased in AD patients when a complication occurs, such as
      folate/cobalamin deficiency or a cardiovascular disease.

PMID- 15254924
TI  - Effect of combined support for people with dementia and carers versus regular day
      care on behaviour and mood of persons with dementia: results from a multi-centre
      implementation study.
AB  - BACKGROUND: A previous study in Amsterdam showed that combined family support in
      the Meeting Centres Support Programme, in which dementia patients and their
      carers are both supported by one professional staff member, is more effective in
      influencing behaviour problems and mood of dementia patients living in the
      community than non-integrated support, such as day care only. OBJECTIVE: A multi
      centre implementation study tests if similar effects are achieved in other
      regions of The Netherlands. METHODS: A pretest-posttest control group design was
      applied. 112 dementia patients who visited psychogeriatric day care in eight
      community centres across the country and in three nursing homes, and their carers
      participated in the study. The patients in the experimental group (n = 89)
      received support from the Meeting Centres Support Programme together with their
      carers, while the control group (n = 23) received day care only. Behaviour
      problems (agressive behaviour, inactivity, non-social behaviour) and mood
      (dissatisfaction, depressive behaviour) were assessed using standardized
      observation scales. Quality of life was assessed by interviewing the patients.
      RESULTS: After 7 months the Meeting Centres Support Programme, compared to
      regular day care, showed a moderately positive effect on the degree of total
      behaviour problems (effect size = 0.52), especially on inactivity (effect size =
      0.37) and non-social behaviour (effect size = 0.60), a large effect on depressive
      behaviour (effect size = 0.92) and a moderate effect on self-esteem (effect size
      = 0.43). CONCLUSIONS: The Meeting Centres Support Programme proves to be more
      effective than regular day care in influencing behaviour problems, especially
      inactivity and non-social behaviour, and depressed mood. Participation in the
      programme also seems to have a positive effect on self-esteem, an important
      aspect of quality of life. These findings surpass the results of the Amsterdam
      study and confirm the surplus value of the combined family support in the Meeting
      Centres Support Programme as compared to regular day care for people with mild to
      severe dementia.

PMID- 15254925
TI  - Scoring clock tests for dementia screening: a comparison of two scoring methods.
AB  - OBJECTIVE: To compare the dementia screening performance of two scoring systems
      of the clock drawing test. METHODS: A sample of 1199 elderly subjects was
      administered the clock drawing test as part of a study on aging and dementia. The
      clock drawings were scored using published criteria for the two scoring systems
      that were compared. Additionally, a selection of 103 drawings was scored by three
      different raters to evaluate inter-rater agreement within each of the two
      methods. For a selection of 473 drawings the final diagnosis on the presence or
      absence of dementia was known. For these drawings accuracy for the detection of
      dementia was compared between the two methods. RESULTS: The four-item scoring
      system (Kappa 0.76; sensitivity 0.97; specificity 0.32; PPV 0.53; NPV 0.93) was
      found to be a little more reliable and as accurate as the six-item scoring system
      (Kappa 0.67; sensitivity 0.96; specificity 0.42; PPV 0.56; NPV 0.94). CONCLUSION:
      Since both scoring systems showed largely similar results, primary care
      physicians and other health care providers should be encouraged to use the four
      item scoring checklist as it is easier and requires less time than the more
      elaborate checklist of the six-item system.

PMID- 15254926
TI  - Association between subcortical vascular disease on CT and neuropathological
      findings.
AB  - BACKGROUND: Small vessel cerebrovascular disease (svCVD) causes cognitive
      impairment and predicts poorer outcomes in elderly persons. The demonstration of
      svCVD by structural imaging such as computed tomography (CT) is central to the
      clinical diagnosis but its accuracy is uncertain. OBJECTIVE: The aim of this
      study was to assess the validity of CT to detect pathologically verified svCVD.
      METHODS: Leukoaraiosis, patchy lesions, and lacunes were assessed separately in
      different cerebral regions on CT scans of 87 elderly persons with Mini-Mental
      State Examination scores between 0 and 30 enrolled in the OPTIMA project. We
      rated small vessel disease on pathology separately in the white matter and basal
      ganglia as absent/mild, moderate, and severe. The presence of microinfarcts was
      also noted. RESULTS: The severity of all types of CT lesions was associated with
      pathological findings. Subjects with absent/mild leukoaraiosis on CT decreased
      and those with severe leukoaraiosis increased with increasing severity of
      subcortical small vessel ratings on pathology (31, 18 and 0%; 17, 23 and 50%,
      respectively; p = 0.028). A similar association was present for patchy lesions
      (73, 59 and 17%; 7, 18 and 33%, respectively; p = 0.004) and lacune (83, 77 and
      50%; 0, 4 and 17%, respectively; p = 0.023). Leukoaraiosis, patchy lesions, and
      lacunes on CT were associated also with microinfarcts on pathology (p < 0.05).
      CONCLUSION: The standardized assessment of svCVD on CT films at the time of the
      diagnosis correlates with small vessel disease on pathology at death.

PMID- 15254927
TI  - Executive control and the validity of survey data.

PMID- 15254928
TI  - How early are initial symptoms recognized in Korean patients with Alzheimer's
      disease?

PMID- 15254929
TI  - Early onset vs late onset non-psychotic, non-melancholic unipolar depression.

PMID- 15254930
TI  - Personality disorder masquerading as dementia: a case of apparent Diogenes
      syndrome.

PMID- 15254931
TI  - Recent failures of new potential symptomatic treatments for Parkinson's disease:
      causes and solutions.
AB  - One major goal of current research in Parkinson's disease (PD) is the discovery
      of novel agents to improve symptomatic management. The object of these new
      treatments should be to provide effective symptom control throughout the course
      of the disease without the development of side effects such as motor and
      psychiatric complications. Results of several clinical trials of new treatment
      options reported in the past 2 years have shown negative or unsatisfactory
      results. Most of the drugs and surgical procedures used in these studies had been
      tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys
      as well as in the classic 6-hydroxydopamine-lesioned rat model. They raise
      several questions about the true reliability of animal studies, the adequacy of
      the working hypotheses and design of clinical trials, the validity of tools in
      current use to evaluate a specific effect, and the selectivity of the drugs used.
      All these factors may explain failure. This review focuses on pharmacological and
      surgical treatments tested to improve the management of patients with motor
      fluctuations and dyskinesias. Some of the recent trials and possible reasons for
      their lack of success are critically analysed. Finally, some suggestions to avoid
      further failures and improve results are proposed.

PMID- 15254932
TI  - The movement disorder of Maurice Ravel.
AB  - It has long been known that in the last years of his life Maurice Ravel (1875
      1937) suffered from a progressive neurological illness. Despite several proposed
      diagnostic hypotheses, the precise nature of his illness remains elusive.

PMID- 15254933
TI  - Patterns of EMG-EMG coherence in limb dystonia.
AB  - Dystonia of the limbs may be due to a wide range of aetiologies and may cause
      major functional limitation. We investigated whether the previously described
      pathological 4 to 7 Hz drive to muscles in cervical dystonia is present in
      patients with aetiologically different types of dystonia of the upper and lower
      limbs. To this end, we studied 12 symptomatic and 4 asymptomatic carriers of the
      DYT1 gene, 6 patients with symptomatic dystonia due to focal basal ganglia
      lesions, and 11 patients with fixed dystonia, a condition assumed to be mostly
      psychogenic in aetiology. We evaluated EMG-EMG coherence in the tibialis anterior
      (TA) of these and 15 healthy control subjects. Ten of 12 (83%) of symptomatic
      DYT1 patients had an excessive 4 to 7 Hz common drive to TA, evident as an
      inflated coherence in this band. This drive also involved the gastrocnemius,
      leading to co-contracting electromyographic bursts. In contrast, asymptomatic
      DYT1 carriers, patients with symptomatic dystonia, patients with fixed dystonia,
      and healthy subjects showed no evidence of such a drive or any other
      distinguishing electrophysiological feature. Moreover, the pathological 4 to 7 Hz
      drive in symptomatic DYT1 patients was much less common in the upper limb, where
      it was only present in 2 of 6 (33%) patients with clinical involvement of the
      arms. We conclude that the nature of the abnormal drive to dystonic muscles may
      vary according to the muscles under consideration and, particularly, with
      aetiology.

PMID- 15254934
TI  - CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease
      activity.
AB  - Lack of a biomarker of disease activity has hindered the therapy of childhood
      opsoclonus-myoclonus syndrome (OMS), which is purported to be mediated humorally.
      To determine if the cerebrospinal fluid (CSF) B lymphocyte, which may traffic
      into the central nervous system (CNS) to produce antibody locally, is one such
      biomarker, B lymphocytes were immunophenotyped in the CSF and blood of 56
      children with OMS and 26 pediatric controls by dual-laser flow cytometry.
      Neurological severity was rated blindly from videotapes using a validated 12-item
      motor evaluation scale. Children with OMS manifested a 4- to 7-fold higher
      percentage of total B-cells in CSF (P < 0.0001), including CD5(+) (P = 0.001) and
      CD5(-) (P = 0.0004) B-cell subsets, compared with controls, in whom the
      percentages were negligible and unchanging with age. CSF expansion of both B-cell
      subsets increased with disease severity and decreased with disease duration (P
      </= 0.0001, ANOVA). Previous treatment with conventional immunotherapies,
      chemotherapy, or tumor resection had not normalized B-cell percentages in those
      with lingering symptoms. These studies reveal that CSF B-cell expansion in OMS is
      characteristic and often persistent. Presence of the autoreactive CD5(+) B-cell
      subset and correlations with neurological severity and disease duration suggest
      CSF B-cell expansion is a biomarker of disease activity and possible target for B
      cell-specific therapy. Immunophenotyping of CSF lymphocytes by flow cytometry
      yields valuable clinical information missed by routine studies and allows crucial
      treatment decisions to be made rapidly.

PMID- 15254935
TI  - Deficits in ocular and manual tracking due to episodic ataxia type 2.
AB  - Four patients with a novel mutation leading to episodic ataxia type 2 were
      studied in a task that required them to track target motion either with the eyes
      or with the index finger of the right hand. The target initially moved in a
      straight line and then changed direction at an unpredictable time by an
      unpredictable amount. On the day of testing, 3 of the patients were evaluated as
      normal on a neurological exam, whereas the fourth was severely ataxic.
      Nevertheless, all 4 showed deficits in tracking behavior with common features.
      Ocular tracking tended to result in hypermetric saccades at longer than normal
      latencies. Smooth pursuit tracking was absent in 1 patient and had lower than
      normal gain in the others. Deficits in manual tracking showed similarities to the
      deficits in ocular tracking, with hypermetric compensations for changes in target
      direction. The similarities in the deficits in manual and ocular tracking suggest
      that they are subject to similar control by the cerebellar structures.

PMID- 15254936
TI  - Natural history and syndromic associations of orthostatic tremor: a review of 41
      patients.
AB  - Orthostatic tremor (OT) is a rare condition characterized by unsteadiness when
      standing still that is relieved when sitting or walking and is thought to arise
      from a central generator in the cerebellum or brainstem. OT is considered to be a
      distinct, discrete condition, and little is known about its demographic
      characteristics, natural history, associated features, and treatment response. We
      have reviewed these aspects in 41 OT patients fulfilling current diagnostic
      criteria, seen at our institution between 1986 and 2001. We classified 31 (75%)
      as having idiopathic "primary OT" either with (n = 24) or without an associated
      postural arm tremor. We found that 10 of 41 (25%) cases had additional
      neurological features, and we defined this group as having "OT plus" syndrome. Of
      these 10, 6 had parkinsonism; 4 of these had typical Parkinson's disease (PD), 1
      had vascular and 1 had drug-induced parkinsonism. Among the remaining 4 patients,
      2 had restless legs syndrome (RLS), 1 had tardive dyskinesia, and 1 orofacial
      dyskinesias of uncertain etiology. One patient with PD and the patient with
      vascular parkinsonism also had RLS. Age at onset was significantly earlier in the
      "primary OT" (mean +/- SD, 50.4 +/- 15.1) than in the "OT plus" (61.8 +/- 6.4; z
      = 2.7; P =.006) group. In 7 of the 10 "OT plus" patients, OT leg symptoms
      preceded the onset of additional neurological features. OT appeared to be
      underdiagnosed, and on average, it took 5.7 years from the initial complaints
      until a diagnosis was made. In general, treatment response to a variety of drugs
      such as clonazepam, primidone, and levodopa was poor. In most cases, OT symptoms
      remain relatively unchanged over the years, but in 6 of 41 cases (15%), the
      condition gradually worsened over the years, and in some of these cases, symptoms
      spread proximally to involve the trunk and arms. OT may not be a discrete
      disorder as commonly believed and associated features like parkinsonism present
      in nearly 25% of cases. Dopaminergic dysfunction may have a role in the
      pathophysiology of this disorder.

PMID- 15254937
TI  - Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.
AB  - The frequency and relative contribution of DJ-1 mutations in early-onset
      Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD
      patients (mean age at onset of PD +/- SD, 41.5 +/- 7.2 years), ascertained
      independent of family history, who participated in a study of the genetic
      epidemiology of PD. This study includes sequence analysis of the DJ-1 gene in
      addition to assaying the 14,082-bp deletion spanning exons 1 to 5, previously
      identified in a Dutch kindred, in 89 EOPD cases. A heterozygous missense mutation
      in exon 5 (A104T) was identified in an EOPD case of Asian ethnicity; this
      sequence variant was absent in 308 control chromosomes. We identified additional
      sequence variation in the DJ-1 gene, including a polymorphism in the coding
      region in exon 5 (R98Q), three polymorphisms in the 5' untranslated region (exon
      1A/1B), and two polymorphisms in intronic regions (IVS1 and IVS5). Mutations in
      the DJ-1 gene are rare in EOPD in both sporadic and familial cases.

PMID- 15254938
TI  - Visual hallucination in Parkinson's disease with FDG PET.
AB  - To determine the characteristics of cerebral glucose metabolism in Parkinson's
      disease patients with visual hallucinations, group comparison studies using
      [18F]fluorodeoxyglucose positron emission tomography were performed. Nondemented
      Parkinson's disease patients in advanced stages were classified into two groups:
      (1) patients without visual hallucinations; (2) patients with visual
      hallucinations. Compared to patients without hallucinations, the relative
      regional cerebral glucose metabolic rate was greater in the frontal areas in
      patients with visual hallucinations, and the increase reached a significant level
      in the left superior frontal gyrus. Relative frontal hypermetabolism may be a
      feature of Parkinson's disease patients with visual hallucinations.

PMID- 15254939
TI  - Tumor diagnosis preceding Parkinson's disease: a case-control study.
AB  - Lower cancer risk in Parkinson's disease (PD) patients compared to the general
      population has been reported. However, most of the studies were based on death
      certificates. We designed a case-control study to estimate the association of
      tumor preceding PD onset and PD. PD patients were matched by age and gender to PD
      free individuals, randomly selected from the municipalities of residence of
      cases. Occurrence of tumors preceding PD onset was assessed through a structured
      questionnaire. Neoplasms were categorized as benign, malignant, or of uncertain
      classification, and endocrine-related or not. Odds ratios (OR) were calculated
      using conditional logistic regression and adjusted for tumor categories and risk
      factors. We included 222 PD patients. Frequency of cancer was 6.8% for cases,
      12.6% for controls. PD patients had a decreased risk for neoplasms (adjusted OR,
      0.4; 95% confidence interval [CI], 0.2-0.7). Risk was reduced only for women
      (adjusted OR, 0.3; 95% CI, 0.1-0.7). PD patients had a decreased risk both for
      malignant (adjusted OR, 0.6; 95% CI, 0.1-2.5) and nonmalignant neoplasms
      (adjusted OR, 0.3; 95% CI, 0.1-0.7). Still, risk was decreased for endocrine
      related tumors (adjusted OR, 0.3; 95% CI, 0.1-0.9) and non-endocrine-related
      tumors (adjusted OR, 0.4; 95% CI, 0.1-0.9). Our study confirms the inverse
      association between PD and neoplasms reported in previous epidemiologic studies.

PMID- 15254940
TI  - A consanguineous Turkish family with early-onset Parkinson's disease and an exon
      4 parkin deletion.
AB  - The importance of parkin in early-onset Parkinson's disease in Japan, Europe, and
      the United States is well established. The contribution of this gene to the risk
      of Parkinson's disease in other populations is less well known. To explore the
      importance of parkin in those of Turkish ancestry, we studied familial cases from
      that country, and identified a consanguineous family with early-onset Parkinson's
      disease due to a homozygous mutation in parkin.

PMID- 15254941
TI  - Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal
      degeneration.
AB  - Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral
      benzodiazepine receptor binding sites, offers the opportunity to image activated
      microglia in vivo. This tool may therefore be used to display the occurrence of
      microglial activation in the course of neurodegeneration. A patient with the
      clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was
      studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked
      right hemispheric hypometabolism and asymmetric microglial activation in
      corresponding areas of the basal ganglia and right temporal and parietal cortex.
      [(11)C]PK 11195 PET suggests involvement of microglial activation in the
      pathogenesis of CBD.

PMID- 15254942
TI  - Clinical characteristics of Parkinson's disease among Inuit in Greenland and
      inhabitants of the Faroe Islands and Als (Denmark).
AB  - In earlier studies, we found high age-adjusted prevalences of Parkinson's disease
      (PD) in the Faroe Islands (209 per 100,000 inhabitants) and in Greenland (187.5
      per 100,000 inhabitants) compared to the age-adjusted prevalence on the island of
      Als in the southern part of Denmark (98.3 per 100,000 inhabitants). We thoroughly
      examined patients with suspected parkinsonism using internationally accepted
      diagnostic criteria. In the present study, we found no significant clinical
      differences between patients with PD in the three areas, despite this high
      difference in prevalence. However, comparing the age at examination and age at
      treatment, the patients were younger in Greenland, a higher proportion of
      patients had cognitive decline, and they had a higher mean Hoehn and Yahr rating
      score, although they received a lower levodopa dose. A higher proportion of the
      patients in Greenland were newly diagnosed than in the other two areas.

PMID- 15254944
TI  - Risus sardonicus after thalamic haemorrhage.
AB  - We describe an uncommon movement disorder after stroke. A 70-year-old man was
      admitted for a right thalamic haemorrhage and 1 week later developed bilateral
      contractions of the face. Electromyographic study revealed a bilateral facial
      dystonia. The association of this bilateral facial dystonia and vertical gaze
      palsy produced the aspect of a "risus sardonicus."

PMID- 15254943
TI  - Assessing comorbidity in patients with Parkinson's disease.
AB  - The aim of this study was to assess the accuracy of an interview-based assessment
      of comorbidity, in patients with Parkinson's disease (PD). The Cumulative Illness
      Rating Scale-Geriatric (CIRS-G) was completed (1) in an interview with 31 PD
      patients and their caregivers, and (2) by reviewing the patient's medical charts
      from their general practitioners. Based on the interview, all patients had some
      comorbidity, 84% had one or more moderate comorbid diseases. The most frequently
      affected organ systems were "lower gastrointestinal" and "genitourinary". The
      mean +/- SD total score of the interview-based (chart-based) CIRS-G was 6.9 +/-
      3.8 (7.6 +/- 3.5) with a mean of 4.3 +/- 1.9 (5.0 +/- 1.9) affected organ systems
      and a mean of 2.1 +/- 1.7 (2.3 +/- 1.6) organ systems with at least moderate
      comorbidity per patient. The agreement (intraclass correlation coefficients)
      between the interview-based and chart-based assessments for the six summary
      scores ranged from 0.69 to 0.81. The agreement for the 14 organ systems ranged
      from 0.13 to 1.00 (weighted kappa); 12 had a K(w) above 0.40 (moderate
      agreement). The comorbidity summary scores had a moderate correlation with age
      and disability. The interview-based assessment of the CIRS-G is easy to apply and
      is an accurate method to assess comorbidity in patients with PD.

PMID- 15254945
TI  - Long-term outcome of clozapine use for psychosis in parkinsonian patients.
AB  - A retrospective analysis was carried out on 39 parkinsonian patients on clozapine
      treatment >/=24 months for psychosis. The cohort had a mean age of 76 years and
      an average clozapine dose of 47 mg/day over 60 months of clozapine use. Of 39
      patients, 13 (33%) patients were eventually admitted to nursing homes, 6 (46%) of
      whom died over a period of 5 years. The overall 5-year mortality rate in this
      cohort was 44% (17/39). Of 39 patients, 33 (85%) had continued partial/good
      response and 5 (13%) had complete resolution of psychosis. None discontinued
      clozapine due to motor worsening. Among patients who responded early on, the long
      term efficacy of clozapine for psychosis was sustained. The risk of nursing home
      placement and mortality among parkinsonian patients treated with clozapine for
      psychosis in this geriatric cohort was better than that reported previously. Our
      data are more consistent with recently published long-term outcome data
      suggesting an improvement in the prognosis of parkinsonian patients with
      psychosis with the use of atypical antipsychotic agents such as clozapine.

PMID- 15254946
TI  - Chorea-acanthocytosis associated with Tourettism.
AB  - We report on a case of Chorea-acanthocytosis (ChAc) in association with
      Tourettism that consisted of motor and vocal tics, attention deficit
      hyperactivity disorder, and obsessive-compulsive disorder in addition to the
      typical symptoms of ChAc. The subject was compared with his elder sister who had
      the same disease but milder clinical profile and neuroradiological findings. The
      [(18)F]-2-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) findings
      did not explain the differences in symptomatology between the patient and his
      sister, although they may have correlated with severity.

PMID- 15254947
TI  - Vascular hemichorea/hemiballism and topiramate.
AB  - Although vascular hemichorea/hemiballism (HC/HB) has been reported to be self
      limited, in some cases, it can be irreversible and severely disabling. The
      standard treatment includes typical and atypical neuroleptics and GABA-mimetic
      drugs. Topiramate is a new antiepileptic drug possessing a complex mechanism of
      action, including the enhancement of GABA-mediated inhibition. We describe a 71
      year-old patient with HC/HB who markedly improved after topiramate treatment.

PMID- 15254949
TI  - Amphetamine-induced chorea in attention deficit-hyperactivity disorder.
AB  - Attention deficit-hyperactivity disorder (ADHD) is treated frequently with
      stimulants in both children and adults. While tics are occasional complications
      of stimulant therapy, chorea is reported rarely. We describe an adult ADHD
      patient who developed chorea upon dose escalation of mixed amphetamine salts,
      which resolved on discontinuation of the drug.

PMID- 15254948
TI  - Mistaken diagnosis of psychogenic gait disorder in a man with status
      cataplecticus ("limp man syndrome").
AB  - We report on a 45-year-old man with a history of multiple psychiatric admissions
      for a gait disorder and episodic weakness thought to be psychogenic who was
      subsequently diagnosed with status cataplecticus due to narcolepsy. The gait
      difficulties resolved with venlafaxine. This case demonstrates that status
      cataplecticus can be misdiagnosed as a psychogenic gait disorder.

PMID- 15254950
TI  - Unusual forehead tremor in a patient with essential tremor.
AB  - Voice and head (neck) tremor commonly occur in patients with essential tremor
      (ET), but involvement of cranial musculature is generally limited to these
      specific cranial structures, and action tremor of the forehead has not been
      reported. We describe a patient with ET who had forehead tremor. The tremor
      seemed to be task-specific, and neurophysiological features suggested that the
      forehead tremor was dystonic. The presence of forehead tremor in a patient with
      ET probably indicates an additional pathophysiologic process. The explanation for
      the specificity of involvement of cranial musculature in ET is not known, but
      this clinical observation might help guide investigators who are interested in
      the underlying pathophysiology of this condition.

PMID- 15254951
TI  - Refined linkage to the RDP/DYT12 locus on 19q13.2 and evaluation of GRIK5 as a
      candidate gene.
AB  - By examining two previously described families with rapid-onset dystonia
      parkinsonism, we have identified a key recombination event that places the
      disease locus (DYT12) into a 5.9 cM interval flanked by markers D19S224 and
      D19S900. Evaluation of a positional candidate gene, the glutamate receptor
      subunit GRIK5, revealed no mutations.

PMID- 15254952
TI  - Spinocerebellar ataxia type 2 with Levodopa-responsive parkinsonism culminating
      in motor neuron disease.
AB  - We describe an exceptional spinocerebellar ataxia type 2 (SCA2) phenotype
      combining cerebellar ataxia, levodopa-responsive parkinsonism, and motor neuron
      symptoms. We conclude that motor neuron symptoms and signs may be a striking
      manifestation in SCA2, masking pre-existing cerebellar and extrapyramidal
      semeiology.

PMID- 15254953
TI  - Pregnancy in stiff-limb syndrome.
AB  - To our knowledge, pregnancy in a patient with stiff-limb-syndrome (SLS) has not
      been reported. We present the case of a woman with SLS who improved during
      pregnancy, delivered a normal healthy baby by forceps-assisted vaginal delivery,
      and suffered a mild postpartum "relapse."

PMID- 15254954
TI  - Markedly asymmetrical parkinsonism as a leading feature of adult-onset
      Huntington's disease.
AB  - We report on a 28-year-old man who presented with right hand tremor,
      bradykinesia, and rigidity of his right side extremities. Our case report
      emphasizes that markedly asymmetrical parkinsonism can be an initial presentation
      of adult-onset Huntington's disease (HD), and different clinical presentations
      can be observed in members of an individual HD family with the same CAG repeat
      length.

PMID- 15254955
TI  - Distressing belching and neuroacanthocytosis.
AB  - We report on an uncommon manifestation of molecularly proven neuroacanthocytosis
      in a 32-year-old man in whom dyspnea with desaturation while awake accompanied by
      continuous involuntary belching were the major consequences of the disease.

PMID- 15254956
TI  - Observations on the human rejection behaviour syndrome: Denny-Brown revisited.
AB  - The parietal avoiding-rejection behaviour syndrome, first described by Denny
      Brown in the rhesus monkey, has been reported only rarely in humans. Here, we
      describe a patient with rejection behaviour in the setting of progressive
      cognitive decline accompanied by cortical myoclonus.

PMID- 15254957
TI  - Re: Lack of association between progressive supranuclear palsy and arterial
      hypertension: a clinicopathological study.

PMID- 15254958
TI  - The myth of microelectrode recording in ensuring a precise location of the DBS
      electrode within the sensorimotor part of the subthalamic nucleus.

PMID- 15254959
TI  - Primary mouse embryonic fibroblasts: a model of mesenchymal cartilage formation.
AB  - Cartilage formation is an intricate process that requires temporal and spatial
      organization of regulatory factors in order for a mesenchymal progenitor cell to
      differentiate through the distinct stages of chondrogenesis. Gene function during
      this process has best been studied by analysis of in vivo cartilage formation in
      genetically altered mouse models. Mouse embryonic fibroblasts (MEFs) isolated
      from such mouse models have been widely used for the study of growth control and
      DNA damage response. Here, we address the potential of MEFs to undergo
      chondrogenic differentiation. We demonstrate for the first time that MEFs can
      enter and complete the program of chondrogenic differentiation ex vivo, from
      undifferentiated progenitor cells to mature, hypertrophic chondrocytes. We show
      that chondrogenic differentiation can be induced by cell-cell contact or BMP-2
      treatment, while in combination, these conditions synergistically enhance
      chondrocyte differentiation resulting in the formation of 3-dimensional (3-D)
      cartilaginous tissue ex vivo. Temporal expression profiles of pro-chondrogenic
      transcription factors Bapx1 and Sox9 and cartilaginous extracellular matrix (ECM)
      proteins Collagen Type II and X (Coll II and Coll X) demonstrate that the in vivo
      progression of chondrocyte maturation is recapitulated in the MEF model system.
      Our findings establish the MEF as a powerful tool for the generation of
      cartilaginous tissue ex vivo and for the study of gene function during
      chondrogenesis.

PMID- 15254960
TI  - Effects of Helicobacter pylori infection on cell cycle progression and the
      expression of cell cycle regulatory proteins.
AB  - Helicobacter pylori lives in the stomach lumen adhering and specifically
      interacting with gastric epithelial cells. H. pylori infection can cause a broad
      range of diseases. Although most infected individuals only develop a chronic
      inflammation of the stomach, some patients progress to chronic gastritis,
      duodenal ulceration, or, rarely, cancer. H. pylori is able to send and to receive
      signals from the gastric epithelium, allowing host and bacteria to become linked
      in a dynamic equilibrium. Several studies have demonstrated that H. pylori
      infection induces morphological changes of gastric epithelial cells other than
      cell proliferation, increase of mitosis and mutations. It has also been
      demonstrated that H. pylori may predispose to cancer by altering gastric
      epithelial cell turnover acting specifically on transcription factors. Although
      H. pylori is able to induce several host responses, it specifically perturbs the
      delicate balance of those factors that usually help to maintain cell homeostasis.
      The study of mechanisms of interaction between the bacterium and gastric cells
      will surely help to prevent the increase and diffusion of malignancies all over
      the world.

PMID- 15254961
TI  - Role of HER receptors family in development and differentiation.
AB  - Members of the epidermal growth factor receptor family of receptor tyrosine
      kinases play a critical role in both development and oncogenesis. The latter is
      suggested by the frequent overexpression of HER-2, EGFR, and HER-3 in some human
      carcinomas, primarily breast and squamous cancer. The biological activities of
      the EGFR family are exerted through various ligand-receptor and receptor-receptor
      interactions. One receptor that plays a central role in this signaling network is
      HER-2/Neu, which is considered the preferred heterodimerization partner for other
      members of the EGFR family. The role of these receptors and their ligands in
      development is discussed, with particular emphasis on their ability to mediate a
      variety of pathways and cellular responses, including proliferation,
      differentiation, and apoptosis.

PMID- 15254962
TI  - VEGF-R2 and neuropilin-1 are involved in VEGF-A-induced differentiation of human
      bone marrow progenitor cells.
AB  - Tumor growth and metastasis require the generation of new blood vessels, a
      process known as neo-angiogenesis. Recent studies have indicated that early tumor
      vascularization is characterized by the differentiation and mobilization of human
      bone marrow cells. Vascular endothelial growth factor-A (VEGF-A) is one of the
      growth factors, which enhances their differentiation into endothelial cells, but
      little is known about the implication of the VEGF-receptor tyrosine kinases and
      about the implication of the VEGF-R co-receptor, neuropilin-1, in this process.
      In this context, the identification of the molecular pathways that support the
      proliferation and differentiation of vascular stem and progenitor cells was
      investigated in order to define the pharmaceutical targets involved in tissue
      vascularization associated with this process. For this purpose, an in vitro model
      of differentiation of human bone marrow AC133+ (BM-AC133+) cells into vascular
      precursors was used. In this work, we have demonstrated for the first time that
      the effect of VEGF-A on BM-AC133+ cells relies on an early action of VEGF-A on
      the expression of its tyrosine kinase receptors followed by an activation of a
      VEGF-R2/neuropilin-1-dependent signaling pathway. This signaling promotes the
      differentiation of BM-AC133+ cells into endothelial precursor cells, followed by
      the proliferation of these differentiated cells. Altogether, these results
      strongly suggest that VEGF inhibitors, acting at the level of VEGF-R2 and/or
      neuropilin-1, by inhibiting differentiation and proliferation of these cells,
      could be potentially active compounds to prevent progenitor cells to be involved
      in tumor angiogenesis leading to tumor growth.

PMID- 15254963
TI  - Different roles of ERK and p38 MAP kinases during tube formation from endothelial
      cells cultured in 3-dimensional collagen matrices.
AB  - In a two-dimensional (2D) culture dish, the major activity of endothelial cells
      is proliferation with limited morphological change. When cultured in a three
      dimensional (3D) collagen gel matrix, endothelial cells undergo a series of
      morphological changes starting with development of intracellular vacuoles and
      followed by cell elongation. Adjacent cells then coalesce to form tube-like
      structures. This process mimics the steps of capillary formation during
      angiogenesis. Using this model, we investigated the roles of extracellular signal
      regulated kinase (ERK) and p38 MAP kinase (p38) in the tube formation from human
      umbilical vein endothelial cells (HUVEC). Proliferating HUVEC gradually lost
      their ability to divide after being transferred to 3D collagen matrices, where
      differentiation became the dominant cellular activity. The transition from
      proliferation to the differentiation state was accompanied by a drastic reduction
      of cyclin-dependent kinases CDC2, CDK4, and retinoblastoma (Rb) protein, but the
      expression of cyclin-dependent kinase inhibitor, p27kip1, was increased.
      Inhibition of p38 by SB203580 partially prevented these changes and increased the
      proliferation rate of HUVEC. However, cells under this condition exhibited
      unusually elongated cell bodies, and they were unable to coalesce to form tube
      structures. Inhibition of ERK neither affected the cell proliferation rate nor
      the expression levels of cell cycle regulators, but it completely blocked tube
      formation by inducing apoptosis, a finding different from the best-known role of
      ERK in cell proliferation in the 2D cell culture systems. We conclude that the
      major function of ERK is to maintain cell viability while p38 plays multiple
      roles in controlling cell proliferation, viability, and morphogenesis during tube
      formation.

PMID- 15254964
TI  - The influence of protein tyrosine phosphatase-1B on Na,K-ATPase activity in lens.
AB  - The abnormal sodium content of many cataracts suggests Na,K-ATPase is vital for
      maintenance of eye lens transparency. Since tyrosine phosphorylation is
      considered a possible regulatory mechanism for Na,K-ATPase, experiments were
      conducted to test the influence of protein tyrosine phosphatase-1B (PTP-1B) on
      Na,K-ATPase activity. Membrane material was isolated separately from porcine lens
      epithelium and fiber cells. Tyrosine phosphoproteins, Na,K-ATPase alpha1
      polypeptide and PTP-1B were examined by Western blot. Na,K-ATPase activity was
      determined by measuring ATP hydrolysis in the presence or absence of ouabain.
      Western blot analysis revealed tyrosine phosphorylation of multiple membrane
      proteins in both lens cell types, the differentiated fiber cells and non
      differentiated epithelium. When membrane material was subjected to
      immunoprecipitation using an antibody directed against Na,K-ATPase alpha1, a
      colocalized phosphotyrosine band was detected in lens fibers but not epithelium.
      Incubation with PTP-1B caused a approximately 50% increase of Na,K-ATPase
      activity in fiber membrane material. Na,K-ATPase activity in lens epithelium
      membrane material was not significantly altered by PTP-1B treatment even though
      PTP-1B was demonstrated to cause dephosphorylation of multiple membrane proteins
      in the epithelium as well as fibers. While endogenous PTP-1B was detected in both
      cell types, endogenous tyrosine phosphatase activity was low in both epithelium
      and fiber membrane material. The results illustrate endogenous tyrosine
      phosphorylation of Na,K-ATPase alpha1 polypeptide in fibers. Na,K-ATPase alpha1
      in lens fibers may be a potential target for PTP-1B.

PMID- 15254965
TI  - Influence of the extracellular matrix on the regulation of cardiac fibroblast
      behavior by mechanical stretch.
AB  - Fibroblasts are responsible in large part for production, organization, and
      turnover of the extracellular matrix (ECM), thereby regulating the fibrotic
      content of the heart. Excessive fibrosis, which has been associated with certain
      forms of hemodynamic overload such as hypertension, is thought to result in
      increased ventricular chamber stiffness, and eventual heart failure. As such, the
      role of mechanical stretch in regulating fibroblast activity is crucial to our
      understanding of healthy and diseased hearts. However, little is known about the
      effects of alterations in the composition of the ECM in regulating
      mechanotransduction in cardiac fibroblasts. In order to address this question,
      rat cardiac fibroblasts were cultured on silastic membranes coated with different
      ECM substrates, and cyclically stretched for various durations. Experiments were
      designed to assess the activation of signaling pathways, as well as changes in
      collagen production, cellular proliferation, and morphology. Mitogen activated
      protein kinase (MAP kinase) was most rapidly activated, and collagen I expression
      was most abundant, in cells stretched on randomly organized collagen, and
      uncoated charged membranes. Regardless of the nature of the ECM substrate,
      stretched cells decreased proliferation, however, this effect was most marked in
      cells stretched on randomly organized collagen. Finally, cells stretched on all
      ECM substrates increased their surface area, but this was observed most
      significantly in cells adherent to aligned collagen, randomly organized collagen,
      and uncoated, charged membranes. Taken together, these results suggest cardiac
      fibroblasts may differentially interpret a mechanical stimulus, in terms of both
      signal transduction, and specific long-term events such as gene transcription,
      based on the composition and organization of the ECM.

PMID- 15254966
TI  - Effect of recombinant porcine IGFBP-3 on IGF-I and long-R3-IGF-I-stimulated
      proliferation and differentiation of L6 myogenic cells.
AB  - Insulin-like growth factor (IGF)-I stimulates both proliferation and
      differentiation of myogenic precursor cells. In vivo, IGFs are bound to one of
      the members of a family of six high-affinity IGF binding proteins (IGFBP 1-6)
      that regulate their biological activity. One of these binding proteins, IGFBP-3,
      affects cell proliferation via both IGF-dependent and IGF-independent mechanisms
      and it has generally been shown to suppress proliferation of cultured cells;
      however, it also may stimulate proliferation depending upon the cell type and the
      assay conditions. Cultured porcine embryonic myogenic cells (PEMCs) produce IGFBP
      3 and its level drops significantly immediately prior to differentiation.
      Additionally, IGFBP-3 suppresses both IGF-I and Long-R3-IGF-I-stimulated
      proliferation of embryonic porcine myogenic cells. In this study, we have
      examined the effects of recombinant porcine IGFBP-3 (rpIGFBP-3) on IGF-I- and
      Long-R3-IGF-I-stimulated proliferation and differentiation of the L6 myogenic
      cell line. L6 cells potentially provide a good model for studying the actions of
      IGFBP-3 on muscle because they contain no non-muscle cells and they do not
      produce detectable levels of IGFBP-3. RpIGFBP-3 suppresses both IGF-I and Long-R3
      IGF-I-stimulated proliferation of L6 cells, indicating that it suppresses
      proliferation via both IGF-dependent and IGF-independent mechanisms. Our data
      also show that rpIGFBP-3 causes IGF-independent suppression of proliferation
      without increasing the level of phosphosmad-2 in L6 cultures. Additionally,
      rpIGFBP-3 suppresses IGF-I-stimulated differentiation of L6 cells. In contrast,
      however, rpIGFBP-3 does not suppress Long-R3-IGF-I-stimulated differentiation.
      This suggests that rpIGFBP-3 does not have IGF-independent effects on L6 cell
      differentiation.

PMID- 15254967
TI  - Effect of calbindin-D28K on cyclosporine toxicity in cultured renal proximal
      tubular cells.
AB  - Cyclosporine A (CsA) is known to have direct toxicity to renal tubular cells. Its
      toxicity may be mediated by intracellular calcium because CsA increases
      intracellular calcium concentration and enhances the activities of calcium
      dependent calpains and caspases. Calbindin-D28k, a cytosolic calcium binding
      protein, has been used as an intracellular Ca2+ buffer to reduce calcium-mediated
      cytotoxicity in non-renal cells such as neuronal cells. We investigated the
      effects of gene transfer of calbindin-D28k cDNA on CsA cytotoxicity and
      intracellular calcium concentration ([Ca2+]i) in cultured murine proximal tubular
      (MCT) cells. A plasmid containing calbindin-D28k cDNA under the control of CMV
      promoter was transfected to MCT cells with liposomes. Cytotoxicity was assessed
      by LDH release and cell viability assay, and [Ca2+]i was measured ratiometrically
      with fura-2. Compared with MCT cells, cells transfected with calbindin-D28k cDNA
      showed a reduction in LDH release by 27, 30, 32, 33, and 19% (all P < 0.05),
      respectively, after 24 h exposure to 1, 2.5, 5, 10, and 25 microM CsA. Cell
      viability after CsA treatment was also significantly higher in CB cells. A mock
      transfection using plasmid without calbindin-D28k cDNA insert did not affect the
      LDH release or cell viability after CsA treatment. CsA treatment did not affect
      the protein and mRNA abundance of transfected calbindin-D28k cDNA. The expression
      of calbindin-D28k did not affect the baseline [Ca2+]i, but significantly
      suppressed CsA-induced elevation in [Ca2+]i. The expression of calbindin-D28k in
      renal tubular cells provides cytoprotective effects against CsA toxicity,
      probably through its buffering effects on [Ca2+]i.

PMID- 15254969
TI  - High glucose inhibits fructose uptake in renal proximal tubule cells: involvement
      of cAMP, PLC/PKC, p44/42 MAPK, and cPLA2.
AB  - The precise signal that regulates fructose transport in renal proximal tubule
      cells (PTCs) under high glucose conditions is not yet known although fructose has
      been recommended as a substitute for glucose in the diets of diabetic people.
      Thus, we investigated that effect of high glucose on fructose uptake and its
      signaling pathways in primary cultured rabbit renal PTCs. Glucose inhibited the
      fructose uptake in a time- and dose-dependent manner. A maximal inhibitory effect
      of glucose on fructose uptake was observed at 25 mM glucose after 48 h, while 25
      mM mannitol and l-glucose did not affect fructose uptake. Indeed, 25 mM glucose
      for 48 h decreased GLUT5 protein level. Thus, the treatment of 25 mM glucose for
      48 h was used for this study. Glucose-induced (25 mM) inhibition of fructose
      uptake was blocked by pertussis toxin (PTX), SQ-22536 (an adenylate cyclase
      inhibitor), and myristoylated amide 14-22 (a protein kinase A inhibitor). Indeed,
      25 mM glucose increased the intracellular cAMP content. Furthermore, 25 mM
      glucose-induced inhibition of fructose uptake was prevented by neomycin or U
      73122 (phospholipase C inhibitors) and staurosporine or bisindolylmaleimide I
      (protein kinase C inhibitors). In fact, 25 mM glucose increased the total PKC
      activity and translocation of PKC from the cytosolic to membrane fraction. In
      addition, PD 98059 (a p44/42 mitogen-activated protein kinase (MAPK) inhibitor)
      but not SB 203580 (a p38 MAPK inhibitor) and mepacrine or AACOCF3 (phospholipase
      A2 inhibitors) blocked 25 mM glucose-induced inhibition of fructose uptake.
      Results of Western blotting using the p44/42 MAPK and GLUT5 antibodies were
      consistent with the results of uptake experiments. In conclusion, high glucose
      inhibits the fructose uptake through cAMP, PLC/PKC, p44/42 MAPK, and cytosolic
      phospholipase A2 (cPLA2) pathways in the PTCs.

PMID- 15254968
TI  - Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin
      E2 in human mesenchymal stem cells.
AB  - Cyclooxygenase (COX)-2 is generally known as an inducible enzyme, and it produces
      arachidonic acid to prostaglandin E2 (PGE2), which modulates bone metabolism.
      Here, we investigated the expression and role of COX isomers in human mesenchymal
      stem cells. Human mesenchymal stem cells constitutively expressed COX-2 as well
      as COX-1, and secretion of PGE2 was completely inhibited by NS-398, a specific
      inhibitor of COX-2. Levels of secreted PGE2 were strikingly higher in human
      mesenchymal stem cells than in osteoblastic cells differentiated from the
      mesenchymal cells. This higher production of PGE2 in mesenchymal stem cells was
      due to higher expression of membrane-associated PGE synthase (mPGES) regulated by
      early growth response factor-1 (Egr-1). Treatment of human mesenchymal stem cells
      with NS-398 suppressed expression of bone morphogenetic protein-2 (BMP-2). The
      suppression of BMP-2 by NS-398 was abrogated by an EP4 receptor agonist as well
      as by PGE2. Moreover, BMP-2 expression was suppressed by an EP4 receptor
      antagonist. These data indicate that PGE2 produced by COX-2 increases BMP-2
      expression via binding the EP4 receptor.

PMID- 15254970
TI  - Membrane potential and endocytic activity control disintegration of cell-cell
      adhesion and cell fusion in vinculin-injected MDBK cells.
AB  - Cell fusion occurs during fertilization and in the formation of organs such as
      muscles, placenta, and bones. We have developed an experimental model for
      epithelial cell fusion which permits analysis of the processes during junction
      disintegration and formation of polykaryons (Palovuori and Eskelinen [2000] Eur.
      J. Cell. Biol. 79: 961-974). In the present work, we analyzed the process in
      detail. Cell fusion was achieved by microinjecting into the cytoplasm of kidney
      epithelial Madin-Darby bovine kidney (MDBK) cells TAMRA-tagged vinculin, which
      incorporated into lateral membranes, focal adhesions and nucleus, and, prior
      fusion, induced internalization of actin, cadherin and plakoglobin to small
      clusters in cytoplasm. Injected vinculin was still visible at lateral membranes
      after removal of junctional proteins indicating that it was tightly associated
      and perturbed the cell-cell contact sites resulting in membrane fragmentation.
      Injection of active Rac together with vinculin induced accumulation of cadherin
      to the membranes, but did not affect vinculin-membrane association. However, it
      hampered cell fusion probably by supporting adherens junctions. In order to stop
      endocytosis, we lowered intracellular pH of vinculin-injected cells to 5.5 with
      the aid of nigericin in KCl buffer. In acidified cells, injected vinculin
      delineated lateral membranes as thick layers, cadherin remained in situ, and cell
      fusion was completely inhibited. Since this treatment also leads to cell
      depolarization, we checked the vinculin incorporation in a KCl solution
      containing nigericin at neutral pH. In these circumstances, both endogenous and
      injected vinculin delineated lateral membranes as very thin discontinuous layers,
      but still fusion was hampered most likely due to perturbation in the initial
      vinculin-membrane association. We suggest that vinculin might function as a
      sensor of the environment triggering cell fusion during development in
      circumstances where membrane potential and local and transient pH gradients play
      a role.

PMID- 15254971
TI  - Differential signalling of purinoceptors in HeLa cells through the extracellular
      signal-regulated kinase and protein kinase C pathways.
AB  - We have previously shown that HeLa cells express P2Y2 and P2Y6 receptors
      endogenously and determined the pathways by which the P2Y2 controls proliferation
      and Na+/K+ATPase activity. Our objective in this study was to investigate the
      hypothesis that P2Y6 also controls proliferation and Na+/K+ATPase activity; the
      pathways used in these actions were partially characterised. We found that P2Y6
      activation controlled cell proliferation but not the activity of the
      Na+/K+ATPase. UDP activation of P2Y6 provoked: (a) an increase in free cytosolic
      calcium; (b) the activation of protein kinase C-alpha, -beta, -delta, -epsilon,
      and -zeta but not of PKC-iota and -eta; (c) the phosphorylation of the
      extracellular signal-regulated protein kinases 1 and 2 (ERK1/2); (d) the
      expression of c-Fos protein. The P2Y6 induced cell proliferation was blocked by
      the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059, thereby
      indicating that the ERK pathway mediates the mitogenic signalling of P2Y6. PKC
      and phosphoinositide 3-kinase (PI3K) inhibitors were tested at two different time
      points of ERK1/2 phosphorylation (10 and 60 min). The results suggest that novel
      PKCs and PI3K initiate the response but both conventional and atypical PKCs are
      required for the maintenance of the UDP-induced phosphorylation of ERK1/2. The
      induction of c-Fos was greatly diminished by conventional or atypical PKC-zeta
      inhibition, suggesting that it may be due to PKC-alpha/beta and -zeta activity.
      These observations demonstrate that UDP acts as a proliferative agent in HeLa
      cells activating multiple signalling pathways involving conventional, novel, and
      atypical PKCs, PI3K, and ERK. Of these pathways, conventional and atypical PKCs
      appear responsible for the induction of c-Fos, while ERK is responsible for cell
      proliferation and depends upon both novel and atypical PKCs and PI3K activities.

PMID- 15254972
TI  - Molecular identification of ERalpha-positive breast cancer cells by the
      expression profile of an intrinsic set of estrogen regulated genes.
AB  - Estrogens exert a key biological role in mammary gland epithelial cells and
      promote breast carcinogenesis and tumor progression. We recently identified a new
      large set of estrogen responsive genes from breast cancer (BC) cells by DNA
      microarray analysis of the gene expression profiles induced by 17beta-estradiol
      in ZR-75.1 and MCF-7 cells. The purpose of the present study was to test whether
      the expression pattern of hormone regulated genes from this set identifies
      estrogen receptor (ERalpha) positive, hormone responsive BC cells. To this aim,
      we carried out in silico metanalysis of ERalpha positive and ERalpha negative
      human BC cell line transcriptomes, focusing on two sets of 171 and 218 estrogen
      responsive genes, respectively. Results show that estrogen dependent gene
      activity in hormone responsive BC cells is significantly different from that of
      non-responsive cells and, alone, allows to discriminate these two cellular
      phenotypes. Indeed, we have identified 61 genes whose expression profile
      specifically marks ERalpha positive BC cells, suggesting that this gene set may
      be exploited for phenotypic characterization of breast tumors. This possibility
      was tested with data obtained by gene expression profiling of BC surgical
      samples, where the ERalpha positive phenotypes were highlighted by the expression
      profile of a subset of 27 such hormone responsive genes and four additional BC
      marker genes, not including ERs. These results provide direct evidence that the
      expression pattern of a limited number of estrogen responsive genes can be
      exploited to assess the estrogen signaling status of BC cells both in vitro and
      ex-vivo.

PMID- 15254973
TI  - Mechanisms of vascular angiotensin II surface receptor regulation by epidermal
      growth factor.
AB  - We investigated mechanisms by which epidermal growth factor (EGF) reduces
      angiotensin II (AngII) surface receptor density and stimulated actions in
      vascular smooth muscle cells (VSMC). EGF downregulated specific AngII radioligand
      binding in intact cultured rat aortic smooth muscle cells but not in cell
      membranes and also inhibited AngII-stimulated contractions of aortic segments.
      Inhibitors of cAMP-dependent kinases, PI-3 kinase, MAP kinase, cyclooxygenase,
      and calmodulin did not prevent EGF-mediated downregulation of AngII receptor
      binding, whereas the EGF receptor kinase inhibitor AG1478 did. Total cell AngII
      AT1a receptor protein content of EGF-treated and untreated cells, measured by
      immunoblotting, did not differ. Actinomycin D or cytochalasin D, which interacts
      with the cytoskeleton, but not the protein synthesis inhibitor cycloheximide,
      prevented EGF from downregulating AngII receptor binding. Consistently, EGF
      inhibited AngII-stimulated formation of inositol phosphates in the presence of
      cycloheximide but not in the presence of actinomycin D or cytochalasin D. In
      conclusion, EGF needs an intact signal transduction pathway to downregulate AngII
      surface receptor binding, possibly by altering cellular location of the
      receptors.

PMID- 15254974
TI  - Embryonic mouse testis development: role of platelet derived growth factor (PDGF
      BB).
AB  - Platelet-derived growth factors (PDGFs) are paracrine growth factors mediating
      epithelial-mesenchymal interactions and exerting multiple biological activities
      which include cell proliferation, motility, and differentiation. As previously
      demonstrated, PDGFs act during embryonic development and recently, by culturing
      male genital ridges, we have demonstrated that PDGF-BB is able to support in
      vitro testicular cord formation. In the present paper, we report that PDGF-BB is
      present during embryonic testis development and, in organ culture, induces cord
      formation although with reduced diameters compared with the cords formed in the
      genital ridges cultured in the presence of HGF. Moreover we have analyzed the
      roles exerted by this growth factor during the morphogenesis of the testis. We
      demonstrate by immunohistochemical experiments that PDGF-BB and its receptors are
      synthesized by the male UGRs isolated from 11.5 and 13.5 dpc embryos and by
      Western blot that the factor is secreted in a biologically active form by
      testicular cells isolated from 13.5 dpc embryos. The biological roles of the
      factor have also been studied and we demonstrate that PDGF-BB acts as a migratory
      factor for male mesonephric cells whose migration is a male specific event
      necessary for a normal testicular morphogenesis. In addition we demonstrate that
      during testicular development, PDGF-BB induces testicular cell proliferation
      being in this way responsible for the increase in size of the testis. Finally we
      demonstrate that PDGF-BB is able to reorganize dissociated testicular cells
      inducing the formation of large cellular aggregates. However the structures
      formed in vitro under PDGF-BB stimulation never had a cord-like morphology
      similar to the cord-like structures formed in the presence of HGF (Ricci et al.,
      2002, Mech Dev 118:19-28), suggesting that this factor does not act as a
      morphogenetic factor during testicular development. All together the data
      presented in this paper demonstrate that PDGF-BB and its receptors (alpha- and
      beta-subunits) are present during the crucial ages of embryonic mouse testis
      morphogenesis and indicate the multiple roles exerted by this factor during the
      development of the male gonad.

PMID- 15254975
TI  - MyoD induces the expression of p57Kip2 in cells lacking p21Cip1/Waf1: overlapping
      and distinct functions of the two cdk inhibitors.
AB  - The myogenic factor MyoD induces the expression of the cdk inhibitor p21 to
      promote cell cycle withdrawal in differentiating myoblasts. Although the cdk
      inhibitor p57 is also highly expressed in skeletal muscle and is thought to
      redundantly control myogenesis, little is known about its regulation, that has
      been suggested to be independent of MyoD. Here we show, for the first time, that
      MyoD is capable to induce the expression of p57. Intriguingly, this ability is
      restricted to cells lacking p21, suggesting that the two cdk inhibitors may be
      expressed in different muscle cell lineages. We also suggest that the functions
      of p21 and p57 in myoblast cells are only in part redundant. In fact, while the
      two cdk inhibitors play a similar role in cells undergoing G1 arrest during MyoD
      induced differentiation, p57 does not replace p21 in cells escaping G1 arrest and
      undergoing MyoD-induced apoptosis. This difference can be ascribed both to a
      different subcellular localization and to a differential ability of the two cdk
      inhibitors to interact with cell cycle regulators.

PMID- 15254976
TI  - TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding
      domains of TP53 predict poor outcome.
AB  - The aim of this study was to clarify whether specific p53 mutations may have
      biological relevance in terms of disease relapse or death in gastric carcinomas
      (GC). Resected specimens from a consecutive series of 62 patients with GC
      undergoing potentially curative surgery were prospectively studied. The
      mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using
      the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was
      evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations
      of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%)
      occurred in highly conserved domains. According to the p53 specific functional
      domains: 4/20 mutations (20%) were in the L3 loop and 3/20 (15%) in LSH motif.
      Eight of the 56 GC resulted MSI-H, 5 (9%) MSI-L, and 43 (77%) MSI stable (MSS).
      None of the 8 (14%) MSI-H GC showed p53 mutations. p53 mutations were associated
      with intestinal histotype. Moreover, specific mutations in functional domain (L3
      and LSH), together with advanced TNM stage, node involvement, depth of invasion,
      diffuse histotype, proved to be significantly related to quicker relapse and to
      shorter overall survival. Specific mutations in p53 functional domains, rather
      than any mutations in this gene, may be biologically more significant in terms of
      patients outcome, indicating that these mutations might have biological relevance
      to identify subgroups of patients at higher risk of relapse or death who might
      benefit from a more aggressive therapeutic approach.

PMID- 15254977
TI  - US trade policies hamper global cooperation.

PMID- 15254978
TI  - Strap him down or knock him out: Is conscious sedation with restraint an
      alternative to general anaesthesia?

PMID- 15254979
TI  - Misrepresentation of research publications among orthopaedic surgery fellowship
      applicants: a comparison with documented misrepresentations in other fields.

PMID- 15254980
TI  - Routine duodenal biopsies to exclude celiac disease? Not yet.

PMID- 15254981
TI  - Effective endoscopic tattooing technique.

PMID- 15254982
TI  - Classics in epidemiology: should they get it right?

PMID- 15254983
TI  - Spinal congenital dermal sinus associated with thoracic meningocele.

PMID- 15254984
TI  - Euthanasia, physician-assisted suicide, and Christianity's positive relationship
      to the world.
AB  - This essay addresses the problem of communication between Christianity and the
      secular world in an area where the latter tends to oppose the moral norms
      endorsed by the former. How, in the interest of missionary outreach (and with
      which understandings of what such outreach involves) can the language barriers be
      bridged? Whereas the Roman Catholic natural law tradition posits a neutral common
      ground of (traditional or hermeneutical) rationality between Christianity and the
      world, an Ebeling- and Barth-modified Lutheranism engages in an argument ad
      hominem by seizing upon an admitted deficiency within that world, and by
      recommending Christianity for mending that deficiency. Both positions differ from
      the Evangelical claim that since that which the world politically values is
      derived from Christianity, it must remain subject to Christianity's moral
      legislation. An entirely different approach to the communication- and outreach
      problem is taken by Orthodox Christianity: The gulf which separates it from the
      world is acknowledged, and the possibility of trans-gulf-traffic is referred to
      God's grace. It is only this latter model, however, which preserves
      Christianity's theological terms (such as "Scripture", "law", and "holiness")
      from common-ground-securing, deficiency-mending, or authority-imposing
      secularizing, and thus from compromising that very theological context into which
      communicative outreach endeavors were to invite.

PMID- 15254985
TI  - Evaluation of the effects of aluminium, ethanol and their combination on rat
      brain synaptosomal integral proteins in vitro and after 90-day oral exposure.
AB  - The effects of aluminium lactate (Al-lactate) on the rat cerebral synaptosome
      integral proteins adenosinetriphosphatase (ATPase) and acetylcholinesterase(AChE)
      were studied in vitro and in vivo. Coexposure with ethanol (EtOH) was studied in
      both situations. Isolation of synaptosomes was carried out using isoosmotic
      Percoll gradients. In in vitro experiments, the synaptosomes were exposed to
      different concentrations of Al-lactate in the incubation mixture. Al-lactate
      caused decreases in total ATPase and AChE activities concentration dependently.
      The decrease in ATP activity started at 0.2 mM concentration, and concentration
      for the 50% decrease of the enzyme activity (EC50 ) was 1.1 mM. The decrease in
      AChE activity started at 5-10 mM concentration, and the EC50 value was 15.8 mM.
      Coexposure with ethanol (2 mM) increased the EC50 values similarly in both cases.
      After 90-day oral exposure of rats to Al-lactate (91.8 mg/kg/day), the serum
      aluminium level was 0.9-1.3 ptM/l. Coexposure with EtOH(3.0 g/kg/day) did not
      significantly increase the blood Al(0.7 2.2 pM/l). Aluminium exposure caused a
      decrease in the blood EtOH concentration (0.6 mM/1) compared with blood EtOH
      (12.3 mM/1) in the rats exposed to ethanol only. In the rats studied 2 weeks
      after the Al exposure, the activities of ATPase and AChE were significantly lower
      than in the rats studied immediately after the exposure. Correspondingly, a
      significant decrease in AChE activity was found in Al and EtOH-exposed rats, but
      in the control rats there were no differences between the study groups.
      Immediately after the 90-day dosing, the exposed rats did not differ
      significantly from the control rats. Based on the in vitro results, the neural
      membrane integral proteins ATPase and AChE may be considered as targets for the
      effects of aluminium and ethanol. Ninety-day in vivo exposure of rats to
      aluminium caused decrease in ATPase and AChE activities, detectable 2 weeks after
      the exposure.

PMID- 15254986
TI  - Redefining Medicare's long-term financial health: a closer look at the "Medicare
      funding warning" in the trustees' report.

PMID- 15254987
TI  - Proceedings of the 19th Montreux Symposium on Liquid Chromatography-Mass
      Spectrometry, Supercritical Fluid Chromatography-Mass Spectrometry, Capillary
      Electrophoresis-Mass Spectrometry and Tandem Mass Spectrometry. November 6-8,
      2002. Montreux, Switzerland.

PMID- 15254988
TI  - Cardiac engineering--deciphering the cardiome.
AB  - Two monumental phenomena have shaped science and medicine in the last century and
      practically changed the world we live in. The first relates to the intimate
      interaction between engineering science and medicine-for example, technology and
      cardiology. The second relates to the globalization of science, the proliferation
      of the internet, and the unprecedented international interaction and scientific
      cooperation in facing difficult multidisciplinary challenges. The beneficial
      combination of these two megaphenomena, accompanied by significant environmental
      and sanitary changes, has greatly improved the quality of life and increased
      longevity around the globe. This conference, and the volume issuing from it, aims
      to explore the application of new developments in the microworld of cells and
      genes to gain better insight into the structure and function of the cardiac
      system, and hence to lead to better therapeutic modalities This multinational
      gathering of outstanding scientists from the various fields of the cardiac
      sciences is a living testimonial to human ingenuity and the spirit of
      international cooperation.

PMID- 15254990
TI  - Proceedings of the Fatigue and Performance Modeling Workshop. June 13-14, 2002,
      Seattle, Washington, USA.

PMID- 15254989
TI  - Prolonging life or hindering death? An Orthodox perspective on death, dying and
      euthanasia.
AB  - This article addresses death as a biological event and attempts to approach it as
      a mystery within the light of the Orthodox Christian theology and tradition.
      First, the value of the last moments of the life of a human being is analyzed;
      then the state of living is differentiated from the state of surviving that
      results, in some extreme cases, from the intrusion of technology in medicine. The
      article elaborates on the sacred and spiritual character of death which, when
      viewed within the light of the Christ's resurrection, is transformed into a great
      blessing. The last part of the article focuses on the newly emerged issue of
      euthanasia and the reasons behind it. It poses certain vital questions that ought
      to be answered before legalization gets on its way. Finally, the conclusion
      summarizes the position of the Orthodox Church of Greece on death, dying and
      euthanasia.

PMID- 15254991
TI  - Physician-assisted suicide and euthanasia: German Protestantism, conscience, and
      the limits of purely ethical reflection.
AB  - In this essay I shall describe and analyse the current debate on physician
      assisted suicide in contemporary German Protestant church and theology. It will
      be shown that the Protestant (mainly Lutheran) Church in Germany together with
      her Roman Catholic sister church has a specific and influential position in the
      public discussion: The two churches counting the majority of the population in
      Germany among their members tend to "organize" a social and political consensus
      on end-of-life questions. This cooperation is until now very successful: Speaking
      with one voice on end-of-life questions, the two churches function as the
      guardians of a moral consensus which is appreciated even by many non-believers.
      Behind this joint service to society the lines of the theological debate have to
      be ree-discovered. First it will be argued that a Protestant reading of the joint
      memoranda has to be based on the concept of individual conscience. The crucial
      questions are then: Whose conscience has the authority to decide? and: Can the
      physician assisted suicide be desired faithfully? Prominent in the current debate
      are Ulrich Eibach as a strict defender of the sanctity of life, and on the other
      side Walter Jens and Hans Kung, who argue for a right to physician assisted
      suicide under extreme conditions. I shall argue that it will be necessary to go
      beyond this actual controversy to the works of Gerhard Ebeling and Karl Barth for
      a clear and instructive account of conscience and a theological analysis of the
      concepts of life and suicide. On the basis of their considerations, a conscience
      related approach to physician assisted suicide is developed.

PMID- 15254992
TI  - Medical killing--an Evangelical perspective.
AB  - Evangelicals are unconditionally opposed to active euthanasia. Indirect
      euthanasia is seen as simply belonging to the risks inherent in any medical
      intervention. Passive euthanasia is accepted if used in order to save the dignity
      of the dying and is seen as merely ceasing to interfere with an irreversible
      dying process. The basis of evangelical ethics is the Bible supplemented by
      science and experience as a kind of natural law. Even though natural law comes
      under Biblical revelation, its acceptance is the reason for the similarity of the
      Evangelical and the Roman-Catholic position of Evangelicals. Evangelicals stress
      the necessity of a better counseling and investment for the deadly ill patient.

PMID- 15254993
TI  - Why physician-assisted suicide perpetuates the idolatory of medicine.
AB  - Adequate response to physician-assisted suicide and euthanasia depends on
      fundamental philosophical and theological issues, including the character of an
      appropriate philosophically and theologically anchored anthropology, where the
      central element of traditional Christian anthropology is that humans are created
      to worship God. As I will argue, Christian morality and moral epistemology must
      be nested within and understood through this background Christian anthropology.
      As a result, I will argue that physician-assisted suicide and euthanasia can only
      be one-sidedly and inadequately appreciated through rational appeal to central
      values, such as "human dignity" and "self determination", or through "sola
      scriptura" biblical interpretation, or individual judgments of conscience.
      Adequately addressing physician-assisted suicide and euthanasia will depend on a
      more fundamental spiritual-therapeutic approach. This cluster of moral,
      epistemological, anthropological, and bioethical claims will be explored by
      drawing on the texts of St. Basil the Great, St. Maximos the Confessor, and St.
      Isaac the Syrian. Their reflections on medicine, the human good, and its
      relationship to worship, spiritual therapy, and God will be used as a basis to
      indicate a broader philosophical perspective, which will be needed to avoid a one
      sided, incomplete approach to the challenges of physician-assisted suicide and
      euthanasia. Medical morality, I argue, is best understood within categories that
      transcend the right, the good, the just, and the virtuous; namely, the holy.

PMID- 15254995
TI  - Abstracts from the 21st European Workshop on Cognitive Neuropsychology.
      Bressanone, Italy. 2003.

PMID- 15254994
TI  - Physician-assisted suicide, euthanasia, and Christian bioethics: moral
      controversy in Germany.
AB  - Discussions in Germany regarding appropriate end-of-life decision-making have
      been heavily influenced by the liberalization of access to physician-assisted
      suicide and voluntary active euthanasia in the Netherlands and Belgium. These
      discussions disclose conflicting moral views regarding the propriety of physician
      assisted suicide and euthanasia, threatening conflicts within not only the
      medical profession, but also the mainline churches in Germany, whose membership
      now entertains views regarding end-of-life decision-making at odds with
      traditional Christian doctrine. On the surface, there appears to be a broad
      consensus supporting the hospice movement and condemning physician-assisted
      suicide and euthanasia. The German Supreme Court has held that treatment
      decisions should, in absence of known patients' wishes, be made in light of
      commonly shared values, unless these violate the principle of "in dubio pro
      vita". The Roman Catholic church and the Evangelical Lutheran church in Germany
      have developed an advance directive for treatment choices at the end of life,
      while condemning physician-assisted suicide and euthanasia. This stance is in
      tension with the strong emerging support for physician-assisted suicide and
      euthanasia, a development that promises to open up foundational disagreements
      within mainline German Christianity regarding the appropriate approach to
      intentionally terminating human life.

PMID- 15254996
TI  - Live discussion: are neurons just too laissez-faire about repair?

PMID- 15254997
TI  - Relational responsibility, and not only stewardship, a Roman Catholic view on
      voluntary euthanasia for dying and non-dying patients.
AB  - The Roman Catholic theological approach to euthanasia is radically prohibitive.
      The main theological argument for this prohibition is the so-called "stewardship
      argument": Christians cannot escape accounting to God for stewardship of the
      bodies given them on earth. This contribution presents an alternative approach
      based on European existentialist and philosophical traditions. The suggestion is
      that exploring the fullness of our relational responsibility is more apt for a
      pluralist--and even secular--debate on the legitimacy of euthanasia.

PMID- 15254998
TI  - Living out the tradition.

PMID- 15254999
TI  - Do humans own themselves ? Questions concerning their self-determination and free
      disposition of self.
AB  - The debate about voluntary euthanasia arises (essentially) from a fundamental
      anthropological question: do humans own themselves? An answer to this question is
      developed which starts out from the foundational ethic of Emmanuel Levinas. The
      metaphysics of the countenance of the Other in Levinas is then related to Karl
      Rahner's description of God as the absolute enigma which is fated towards us.
      God, understood as that enigma, is experienced for us concretely in our
      relationship to the countenance of our neighbor, the other human being. Our being
      thus referred to the absolutely Other in the countenance of the other human
      grounds not only the non-disposability of that other human being, but also the
      non-disposability of myself. This is the decisive point for how one should think
      about euthanasia. In contrast to the (so-called) voluntary euthanasia,
      accompaniment in dying takes account of that dialogical constitution of man.

PMID- 15255000
TI  - Moral philosophy and theology: why is there so little difference for Roman
      Catholics?
AB  - The cardinal question in Christian moral theory and bioethics is whether the
      knowledge that Christians have (1) by grace and (2) by revelation (e.g.,
      regarding the character of human and cosmic history as reaching from creation
      through the Incarnation and the Redemption to the Second Coming and the
      restoration of all things) makes a crucial contribution to understanding
      morality, as for example issues such as the good death and the morality of
      physician-assisted suicide and euthanasia. This article argues that such a
      contribution is made by grace and revelation. The reduction of Roman Catholic
      moral theology and bioethics to secular bioethics is explored, as well as the
      necessity of the unique knowledge possessed by Christians for adequate end-of
      life decision-making.

PMID- 15255001
TI  - The ethical claim of a dying brother.

PMID- 15255002
TI  - Intractable symptoms and palliative sedation at the end of life.

PMID- 15255003
TI  - Leveling the field: answers to frequently asked questions about the Cartagena
      Biosafety Protocol.

PMID- 15255004
TI  - Gene therapy, fundamental rights, and the mandates of public health.
AB  - Recent and near-future developments in the field of molecular biology will make
      possible the treatment of genetic disease on an unprecedented scale. The
      potential applications of these developments implicate important public policy
      considerations. Among the questions that may arise is the constitutionality of a
      state-mandated program of gene therapy for the purpose of eradicating certain
      genetic diseases. Though controversial, precedents of public health jurisprudence
      suggest that such a program could survive constitutional scrutiny. This article
      provides an overview of gene therapy in the context of fundamental rights and the
      mandates of public health.

PMID- 15255005
TI  - Code of ethics and standards.

PMID- 15255006
TI  - Genetic engineering poses new containment challenges.

PMID- 15255007
TI  - New NIH panel to examine possible conflicts of interest.

PMID- 15255008
TI  - When science is just another good cause.

PMID- 15255010
TI  - 50th Anniversary. 10 Year index, volumes 41-50 (1990-1999).

PMID- 15255009
TI  - Using grounded theory to examine people's attitudes toward how animals are used.
AB  - This study uses qualitative methodology to examine why people have different
      attitudes toward different types of nonhuman animal use. Seventeen participants
      took part in a semi-structured interview. The study used Grounded Theory to
      analyze the interviews and developed a model that consists of 4 major themes: (a)
      "attitudes toward animals," (b) "knowledge of animal use procedures," (c)
      "perceptions of choice," and (d) "cost-benefit analysis." The findings illustrate
      that cognitive processing, characteristics of the species of animal being used,
      and the type of animal use can all influence attitudes toward animal use. Because
      previous research has focused on participant variables such as age and gender to
      explain variance in attitudes toward animal use (Furnham & Pinder, 1990; Kellert
      & Berry, 1981) and measured attitudes toward animal use in general (rather than
      distinguishing between different types of use) (Armstrong & Hutchins, 1996),
      these findings can add to knowledge of people's views on animal use. This paper
      discusses how such views may be justified and maintained.

PMID- 15255011
TI  - Ecology: climate-change effect on Lake Tanganyika?

PMID- 15255012
TI  - [A new concept: induction chemotherapy in liver metastasis of colorectal origin].

PMID- 15255013
TI  - [Resection of liver metastasis of colorectal origin following chemotherapy with
      irinotecan].

PMID- 15255014
TI  - [Liver metastasis from colorectal cancer: answers... and still many questions].

PMID- 15255015
TI  - [Surgery of liver metastasis from colorectal cancer following irinotecan and 5FU
      folinic acid].

PMID- 15255016
TI  - [Excision of liver metastasis from colorectal cancer in aged patients].

PMID- 15255017
TI  - Infliximab in the treatment of severe ulcerative colitis.

PMID- 15255018
TI  - Infliximab induces clinical, endoscopic and histological responses in refractory
      ulcerative colitis.
AB  - BACKGROUND: infliximab is a monoclonal antiTNF-ct antibody that has repeatedly
      shown to be effective in the management of Crohn's disease. However, data are
      scarce about its efficacy in ulcerative colitis. AIM: to describe the joint
      experience of three Spanish hospitals in the use of infliximab in patients with
      active refractory ulcerative colitis. PATIENTS AND METHODS: we present seven
      cases of ulcerative colitis (6 with chronic active disease despite
      immunosuppressive therapy, and one with acute steroid-refractory ulcerative
      colitis) treated with infliximab 5 mg/kg of body weight. Clinical response was
      evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after
      initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive
      protein), endoscopic, and histological changes were also assessed. RESULTS: mean
      age of patients was 45.8 +/- 17 years (range 23-77); 4 were female. No adverse
      effects were recorded. Inflammatory activity diminished significantly in 6 of 7
      patients (85.7%; CI 95%: 42-99%) both from a clinical (p = 0.01) and biochemical
      (p <0.05) point of view. Five out of six patients (83.3%; 36-99%) with
      corticosteroid-dependent disease could be successfully weaned off these drugs.
      Five patients were endoscopicly controlled both before and after therapy, and a
      positive endoscopic and histological response could be recorded in all of them.
      CONCLUSION: infliximab may be an effective and safe therapy for some patients
      with ulcerative colitis refractory to other forms of therapy, although controlled
      studies are needed to assess its role in the general management of this disease.

PMID- 15255019
TI  - Prognostic significance of the p185 protein in colorectal cancer.
AB  - The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a
      role in tumor development and progression. The aim of this prospective study was
      to evaluate the prognostic value of p185 protein in colorectal cancer using
      immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens
      from patients who had been operated on by the same surgeon and subjected to a
      median follow-up of 3 years. Thirty-three per cent of patients showed p185
      overexpression related to an advanced stage of the disease. In patients with
      adenocarcinoma tumors of the colon without distant metastases, p185 detection was
      found to be of clinical prognostic relevance (p = 0.06).

PMID- 15255020
TI  - A new neovalve type in short bowel syndrome surgery.
AB  - The objective of this study was to compare the clinical and analytical
      repercussion of a new type of intestinal valve -which can be used in both massive
      resections and right hemicolectomies requiring the elimination of the ileocecal
      valve- on two historical series of patients: one group with ileocolic resections
      and end-to-end anastomoses (EE), and one group with Ricotta valves. We compared
      23 patients with ileocolic resection and end-to-end anastomosis, 15 with
      Ricotta's valve, and 20 patients with a new valve made with a small intestinal
      invagination. There were no statistically significant differences in baseline
      characteristics among patients. Patients with the new valve showed less relevant
      weight loss and fewer stools at 3 months and one year when compared to patients
      with Ricotta's valve, and particularly those with ileocolic resection. Moreover,
      with the new valve technique there was neither colonization of the ileal mucosa
      nor bacterial overgrowth. In conclusion, in massive intestinal resections and
      right hemicolectomies, including the ileocecal valve, the new valve technique
      would be of choice.

PMID- 15255021
TI  - Approaching oropharyngeal dysphagia.

PMID- 15255022
TI  - Obscure gastrointestinal bleeding: a complication of radiation enteritis
      diagnosed by wireless capsule endoscopy.
AB  - Obscure gastrointestinal bleeding is a common disorder and may account for as
      many as 5% of all gastrointestinal hemorrhages. It is often caused by lesions in
      the small intestine, which were very complicated to examine prior to the advent
      of wireless capsule endoscopy. Here we present the case of a 31-year-old woman
      with obscure gastrointestinal bleeding as a complication of radiation enteritis,
      which was diagnosed only after she underwent an examination with wireless capsule
      endoscopy. This technique has proven to be far superior to other radiographic and
      endoscopic methods in diagnosing obscure gastrointestinal bleeding and
      pathologies of the small intestine in general.

PMID- 15255023
TI  - Recurrent Dieulafoy's disease with surgical management: diagnosis by endoscopic
      ultrasonography.
AB  - Dieulafoy's disease is an uncommon but potentially significant cause of
      gastrointestinal bleeding caused by a large-caliber arterial vessel in the
      submucosa, which causes erosion and debilitation of the surrounding mucosa and
      may lead to massive gastrointestinal bleeding. Since endoscopy may prove
      insufficient, echoendoscopy may help in the diagnosis of this condition.
      Echoendoscopy may also help improve endoscopic management using mechanical
      techniques (hemoclips or band ligation) or a combination of thermal techniques
      and injection sclerotherapy, since this allows an accurate localization of the
      submucosal vessel. We present a case illustrating this approach by endoscopic
      ultrasonography, and describe the morphological substrate of this condition.

PMID- 15255025
TI  - [85th anniversary of the journal Revista Espanola de Enfermedades Digestivas ( N
      Extraordinario].

PMID- 15255024
TI  - Clindamycin-induced esophageal ulcer.

PMID- 15255026
TI  - 2002 global update of available data on visual impairment: a compilation of
      population-based prevalence studies.
AB  - PURPOSE: For the past 25 years, the WHO Programme for the Prevention of Blindness
      and Deafness has maintained a Global Data Bank on visual impairment with the
      purpose of storing the available epidemiological data on blindness and low
      vision. The Data Bank has now been updated to include studies conducted since the
      last update in 1994. METHODS: An extensive literature search was conducted in
      international and national scientific and medical journals to identify
      epidemiological studies that fulfilled basic criteria for inclusion in the Data
      Bank, namely a clearly stated definition of blindness and low vision, and
      prevalence rates derived from population-based surveys. Sources such as National
      Prevention of Blindness Programmes, academic institutions or WHO country or
      regional reports were also investigated. RESULTS: Two-hundred-and-eight
      population-based studies on visual impairment for 68 countries are reported in
      detail, providing an up-to-date, comprehensive compilation of the available
      information on visual impairment and its causes globally.

PMID- 15255027
TI  - Methods for a population-based study of the prevalence of and risk factors for
      age-related maculopathy and macular degeneration in elderly European populations:
      the EUREYE study.
AB  - PURPOSE: The aims of the EUREYE study are to evaluate the prevalence of age
      related maculopathy (ARM), including macular degeneration (AMD), in elderly
      European populations, to investigate risk factors for ARM and AMD, especially
      solar radiation and diet, and to measure the impact of these conditions on vision
      related quality of life. METHODS: A population-based cross-sectional study with
      retrospective and current exposure measurements. Risk factor assessment is via
      questionnaires (for lifestyle factors such as smoking and alcohol, dietary risk
      factors, outdoor exposure) and blood analysis. Participants are people aged 65
      and over. The study is carried out in 7 centres with locations spanning north to
      south Europe. The main outcome measure is grading of fundus photographs (for
      stage and type of ARM, using the International ARM Epidemiological Study Group
      grading system).

PMID- 15255028
TI  - Vision-specific health-related quality of life in age-related maculopathy
      patients presenting for low vision services.
AB  - Few studies have examined the effectiveness of low vision rehabilitation for age
      related maculopathy (ARM) patients and its impact on vision-specific health
      related quality of life (HRQoL). However, before a multi-site clinical trial can
      be conducted, appropriate outcome measures need to be identified for ARM patients
      who seek out low vision rehabilitation, including a vision-specific HR QoL
      instrument. The 25-item National Eye Institute Visual Function Questionnaire (NEI
      VFQ-25) was developed to assess vision-specific HRQoL for low vision patients,
      including those with ARM. This study examines the performance of the NEI VFQ-25
      among ARM patients who seek out low vision services and examines its relationship
      with visual acuity and self-reported use of low vision aids. One hundred and
      twenty-seven patients were recruited from a University-affiliated low vision
      clinic. During two telephone interviews, subjects completed the NEI VFQ-25 and a
      short cognitive test and provided information on general health and use of low
      vision aids. Additional information on visual acuity and eye health were
      collected from the medical record. Our results indicate that ARM patients who
      seek out low vision services report significant impairment in their vision
      specific HRQoL. Their NEI VFQ-25 scores were lower compared to other ARM and low
      vision rehabilitation samples previously studied. The VFQ subscales with the
      largest deficits were near and distance visual acuities and psychosocial issues
      (near vision, distance vision, role difficulties, dependency, social functioning,
      mental health). These subscale scores were lower for those with greater visual
      acuity impairment. The VFQ subscale scores most impacted by the disease had wide
      variability and were higher for those who used low vision aids, suggesting that
      the NEI VFQ-25 is suitable for measuring further decline and treatment-related
      improvements. Thus, it should be strongly considered for a multi-site clinical
      trial on the effectiveness of low vision rehabilitation.

PMID- 15255029
TI  - The other histiocytosis.

PMID- 15255030
TI  - Reflux esophagitis: sequelae and differential diagnosis in infants and children
      including eosinophilic esophagitis.
AB  - Gastroesophageal reflux disease (GERD) is a common condition in infants and
      children and has many clinical mimics. Most pediatric pathology departments
      process many mucosal biopsies from the proximal gastrointestinal tract to
      evaluate the presence or absence of reflux esophagitis. Since this subject was
      last reviewed in the 1997 edition of Perspectives in Pediatric Pathology devoted
      to gastrointestinal diseases in children (Dahms BB. Reflux esophagitis and
      sequelae in infants and children. In: Dahms BB, Qualman SJ, eds. Gastrointestinal
      Disease. Perspectives in Pediatric Pathology, vol. 20. Basel: Karger, 1997;14
      34), progress in the field has allowed recognition of additional presenting
      symptoms and treatments of GERD. Histologic criteria for diagnosing reflux
      esophagitis have not changed. However, the entity of eosinophilic esophagitis has
      emerged since 1997 and has been defined well enough to allow it to be
      distinguished from reflux esophagitis, with which it was probably previously
      confused. Refinements (though not simplification!) in the definition of Barrett
      esophagus are still in evolution. This review will summarize these newer concepts
      and briefly review the standards of diagnosis of reflux esophagitis.

PMID- 15255031
TI  - Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm
      infants.
AB  - Until now oligonephropathy to indicate "too few nephrons" has been associated
      with intrauterine growth restriction and experimentally induced abnormalities of
      renal development. The purpose of this study was to determine whether there is
      evidence of abnormal postnatal glomerulogenesis in extremely low birth weight
      preterm infants. Renal autopsy tissue was studied by computer-assisted
      morphometry from 56 extremely premature infants (birth weight < or = 1000 g) and
      10 fullterm infants as controls. Preterm infants were divided into two groups
      (short survival < or = 40 days vs. long survival > or = 40 days). Each group was
      subdivided into those with renal failure (RF) and those with normal renal
      function. Forty-two of 56 preterm infants (75%) were adequate for gestational
      age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly
      decreased in all preterm infants as compared to term controls and correlated
      significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis
      with "basophilic S-shaped bodies" was absent in longer surviving preterm and all
      term infants. RGC of preterm infants surviving > or =40 days with RF were
      significantly less than RGC of those with long survival and no RF (P < 0.001).
      Only this latter group demonstrated increased glomerular size as measured by
      mesangial tuft area and Bowman's capsule area compared to all other groups (P <
      0.001). The kidney continues to form postnatally in preterm neonates, but
      glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF.
      Compensatory mechanisms in longer surviving preterm infants include glomerular
      hypertrophy and mesangial proliferation that could lead to hyperfiltration.

PMID- 15255032
TI  - Placental infarcts, intervillous fibrin plaques, and intervillous thrombi:
      incidences, cooccurrences, and epidemiological associations.
AB  - The incidences, cooccurrences and epidemiological associations at term of the
      three common focal macroscopic placental lesions, infarcts, intervillous fibrin
      plaques (IVFP), and intervillous thrombi (IVT) were investigated as part of a
      population-based case-control study of small-for-gestational age (SGA) infants.
      Five hundred and nine placentas from women delivering SGA infants (10th
      percentile or less for gestational age) and 529 placentas from women delivering
      infants with birthweights appropriate for gestational age were examined using
      fixed protocols for identification of macroscopic lesions and microscopic
      diagnoses. One or more of these lesions were found in 280 placentas (28%),
      including infarcts in 150 (15%), IVFP in 132 (13%), and IVT in 64 (6%).
      Macroscopic misidentifications, particularly of IVFP as infarcts, emphasize the
      need for microscopic diagnoses. There were strong associations between the
      occurrence of any one type of lesion and cooccurrence of either of the other two,
      and these associations were site-dependent: between central (nonmarginal)
      infarcts and central IVFP (P = 0.0023); marginal infarcts and marginal IVFP (P <
      0.0001); and between IVT (all central) and marginal infarcts (P < 0.0001) and
      marginal IVFP (P = 0.012). However, a study of associations between the
      incidences of placentas bearing each of the three lesions and 31 socio
      demographic and pregnancy-related factors showed no associations in common. IVFP,
      an IVFP variant termed "labyrinthine," and IVT did not show any of the
      independent associations demonstrated between infarcts and SGA, pregnancy-induced
      hypertension, nonsmoking, age at first pregnancy, and ethnicity. IVFP had no
      significant associations, and IVT were associated only with male gender. The
      study has shown that IVFP and IVT do not share the important clinical
      associations demonstrated for infarcts, but has not identified the pathogenetic
      factor or factors responsible for the frequent cooccurrence of these lesions. The
      maternal thrombophilias may have such a role.

PMID- 15255033
TI  - Congenital diaphragmatic hernia and chromosomal anomalies: autopsy study.
AB  - In a 10-year review of autopsy records from Lutheran General Hospital (1992
      2002), 13 cases of congenital diaphragmatic hernia (CDH) were found. The fetuses
      ranged between 21 and 35 wk of gestation. Four were born alive and five were
      diagnosed prenatally. The defect was left-sided in 11 cases. Cytogenetic study
      revealed five cases with normal karyotype and three cases with complex
      karyotypes. In five cases, no karyotype was performed. The three complex
      karyotypes were: 46,XX,del(8)(p23.1), 47,XX, +i(12)(p10)[6]/46XX[14] (Pallister
      Killian syndrome), and 47,XY,+der(22)t(11:22) (q23.3:q11.2). The unbalanced
      translocation of chromosomes 11 and 22 in congenital diaphragmatic hernia has not
      been previously described. Three fetuses had heart abnormalities, including one
      which was associated with the 8p deletion. The other two had no karyotype study.
      Neither in this study, nor in the literature, is there a consistent or prevailing
      association between a specific chromosomal anomaly and CDH. The embryologic
      closure of the diaphragmatic leaflets may be mediated by a nonstructural
      chromosomal defect, more than one gene, and/or may be related to abnormalities
      not currently detectable.

PMID- 15255034
TI  - Evaluation of early marrow response in childhood aneuploid acute lymphoblastic
      leukemia: flow cytometric DNA analysis versus standard morphology.
AB  - Despite improved survival rates for childhood acute lymphoblastic leukemia (ALL),
      the relapse rate remains at 20-30%. Early peripheral blood and bone marrow (BM)
      responses have been associated with more favorable outcomes; all current
      children's cancer group (CCG) protocols for ALL require BM evaluation at days 7
      and 14 with subsequent therapy based on the results. Morphologic interpretation
      of aspirate smears during induction chemotherapy is challenging, as the samples
      are often hypocellular, excessively friable, and cytologically altered by drugs.
      We have shown discordancy of day 7 and 14 BM lymphoblast counts using morphologic
      and flow cytometric immunophenotypic analyses (FC). The aim of our study was to
      determine the utility, reliability, and cost effectiveness of lymphoblast
      enumeration using DNA content analysis by flow cytometry (DNA-FC) and to further
      demonstrate the subjectivity of morphologic review. All new cases of ALL had DNA
      FC and FC analyses. The percentage of lymphoblasts as determined by both methods
      was compared for 82 aneuploid cases. Three pathologists independently reviewed
      aspirate smears from 39 bone marrow samples of aneuploid ALL that were obtained
      during early induction. These results were compared among themselves and with the
      results obtained by DNA-FC. We found excellent correlation between the percentage
      of lymphoblasts as determined by DNA-FC and FC (R2 = 0.97) over a range of 0 to
      99%. Pathologic review agreed with the DNA-FC, on average, 68%. The sensitivity,
      specificity, and positive and negative predictive values of morphologic review,
      averaged 53, 84, 78, and 63%, respectively, when using DNA-FC as the "gold
      standard." All three pathologists achieved agreement of lymphoblast percentage by
      morphology in 72%. In our laboratory, the use of DNA-FC equates to one-sixth the
      time and one-half the price of FC per exam. We have shown a strong correlation
      between blast counts determined by DNA-FC and FC. DNA-FC is an objective,
      economical, and reliable method to assess early response in induction marrows
      from aneuploid ALL where morphology is often uninterpretable. This test is highly
      reproducible and available at most pediatric institutions. Prospective studies
      need to be employed to evaluate the effect of more definitive methods (DNA-FC and
      FC) of assessing the early response in bone marrows on prognosis.

PMID- 15255035
TI  - Regional ependymal upregulation of vimentin in Chiari II malformation, aqueductal
      stenosis, and hydromyelia.
AB  - Vimentin, glial fibrillary acidic protein (GFAP) and S-100beta protein were
      studied by immunocytochemistry in the ependyma of patients with Chiari II
      malformations, congenital aqueductal stenosis, and hydromyelia. Paraffin sections
      of brains and spinal cords of 16 patients were examined, 14 with Chiari II
      malformations, most with aqueductal stenosis and/or hydromyelia as associated
      features, and 2 patients with congenital aqueductal stenosis without Chiari
      malformation. Patients ranged in age from 20-wk gestation to 48 years. The
      results demonstrated: 1) in the fetus and young infant with Chiari II
      malformations, congenital aqueductal stenosis, and hydromyelia, vimentin is
      focally upregulated in the ependyma only in areas of dysgenesis and not in the
      ependyma throughout the ventricular system; 2) GFAP and S-100beta protein are not
      coexpressed, indicating that the selective upregulation of vimentin is not simple
      maturational delay; 3) vimentin upregulation also is seen in the ependymal
      remnants of the congenital atretic cerebral aqueduct, not associated with Chiari
      malformation; 4) in the older child and adult with Chiari II malformation,
      vimentin overexpression in the ependyma becomes more generalized in the lateral
      ventricles as well, hence evolves into a nonspecific upregulation. The
      interpretation from these findings leads to speculation that it is unlikely that
      ependymal vimentin is directly involved in the pathogenesis of Chiari II
      malformation, but may reflect a secondary upregulation due to defective
      expression of another gene. This gene may be one of rhombomeric segmentation that
      also plays a role in defective programming of the paraxial mesoderm for the
      basioccipital and supraoccipital bones resulting in a small posterior fossa. This
      interpretation supports the hypothesis of a molecular genetic defect, rather than
      a mechanical cause, as the etiology of the Chiari II malformation.

PMID- 15255036
TI  - Cardiac, aortic, and pulmonary arteriopathy in HIV-infected children: the
      Prospective P2C2 HIV Multicenter Study.
AB  - Arteriopathy in human immunodeficiency virus (HIV)-infected patients is being
      increasingly recognized, especially in children. However, few studies have
      histologically evaluated the coronary arteries in HIV-infected children, and none
      have systematically assessed the aorta and pulmonary arteries. The coronary
      arteries, thoracic aorta, and the main and branch pulmonary arteries from the
      postmortem hearts of 14 HIV-infected children were systematically reviewed for
      vasculopathic lesions and compared with 14 age-matched controls. Findings from
      the HIV-infected children were compared with clinical, laboratory, and other
      postmortem findings. Coronary arteriopathy, seen in seven (50%) of the HIV
      infected children, was primarily calcific, and it was associated with decreased
      CD3 and CD4 peripheral blood counts. Large vessel arteriopathy, seen in 9 (64%)
      of the 14 HIV-infected children, was primarily centered on the vasa vasorum and
      consisted mainly of medial hypertrophy and chronic inflammation. Large vessel
      lesions were associated with increased left ventricular mass z-scores (P = 0.02),
      and 78% of patients with large vessel arteriopathy had postmortem cardiomegaly.
      Coronary and large vessel arteriopathies are common in pediatric HIV-infection
      and have different clinicopathologic features suggesting different pathogenesis.

PMID- 15255037
TI  - Fatal congenital systemic juvenile xanthogranuloma with liver failure.
AB  - This is the second reported patient with systemic juvenile xanthogranuloma (JXG)
      to die with liver failure. The infant was born with multiple skin lesions and
      mild hepatomegaly. Direct hyperbilirubinemia was noted on the 2nd day of life,
      followed by progressive hepatomegaly, cholestasis, and death at 29 days of age.
      At autopsy, nodular tumor infiltrates of JXG were present throughout the liver,
      as well as in skin, abdominal lymph nodes, spleen, and pancreas.

PMID- 15255038
TI  - Endodermal sinus tumor of the parotid gland in a child.
AB  - We report a case of a 16-month-old girl with a primary endodermal sinus tumor
      (EST) of the parotid gland. The girl was admitted to the hospital with a left
      side cervical tumor with a quick growth (within 3 wk). The tumor was surgically
      resected. The gross examination showed a 7.0-cm hemorrhagic and fragmentized
      mass. Diagnosis of an EST was established on the hematoxylin and eosin-stained
      slides from the resected material. Elevated serum alpha-fetoprotein (AFP) levels
      were detected and follow-up examinations of the patient did not show ESTs in
      other locations or other manifestations due to the tumor. The patient received
      chemotherapy after the surgery and remained alive without evidence of disease at
      the time of this writing (2 years after the diagnosis). As far as we know, this
      is the second report in the literature of a parotid gland's EST.

PMID- 15255039
TI  - Acardiac twin with externalized intestine adherent to placenta: unusual
      manifestation of omphalocele.
AB  - TRAP (twin reversed arterial perfusion) syndrome produces an acardiac twin
      (acardiac monster, acardius, acardiacus, chorioangiopagus parasiticus, etc.).
      Acardiacs result from monozygotic multiple births in which three anatomic
      anomalies occur: (1) a fetus' cardiac development is disturbed; (2) artery-artery
      anastomosis carries blood from a normal ("pump") twin to the acardiac; (3) vein
      vein anastomosis carries blood from the acardiac back to the normal twin. Whether
      reversal of blood flow in the acardiac results from or causes cardiac
      dysmorphogenesis has not been resolved. Acardiac twins demonstrate a complex
      constellation of malformations usually thought to result from reversed blood
      flow; omphalocele is particularly common. We report monochorionic monoamnionic
      male twins in which an acardiac twin demonstrated externalized intestines
      adherent to the placenta. The twins were delivered from a 30-year-old
      primigravida mother by cesarean section without maternal complications at 33 w.
      The mother has no significant past medical history. The macerated acardius had a
      4-cm long attenuated umbilical cord with indeterminate number of vessels.
      Structures rostral to the thorax were absent save for one poorly developed hand
      and arm. The abdomen contained loose mesenchyme and no organs. The entire
      intestine (21 cm) along with two testes was located in a sac on the surface of
      the placenta. No histopathologic anomalies of formed structures were identified
      aside from spatial relationships and incomplete development. The normal twin
      required no intensive care and is doing well. To our knowledge, this is the first
      report of externalized intestine, which may represent an unusual consequence of
      omphalocele.

PMID- 15255040
TI  - Malassezia furfur meningitis associated with total parenteral nutrition subdural
      effusion.
AB  - We present a case of Malassezia furfur meningitis arising in a very low birth
      weight infant with chronic lung disease, necrotizing enterocolitis, and
      intraventricular hemorrhage. M. furfur meningitis was probably acquired late
      following successful treatment for earlier systemic central line-associated M.
      furfur infection. M. furfur meningitis has only once been previously reported.
      Unlike the previous case where meningitis was secondary to widespread blood-borne
      dissemination, infection was limited to the leptomeninges and arose in
      association with extravasation of total parenteral nutrition (TPN) and intralipid
      fluid into subarachnoid space via peripheral scalp catheter.

PMID- 15255041
TI  - Splenopancreatic field abnormality is not unique to trisomy 13.
AB  - Splenopancreatic fusion is an uncommon finding, usually only seen as part of the
      splenopancreatic field abnormality associated with trisomy 13. It may present
      itself either as ectopic splenic tissue in the cauda pancreatis, as ectopic
      pancreatic tissue in the spleen or accessory spleen, or as fusion of the cauda
      pancreatis and splenic hilum. In this study, we report four unrelated congenital
      anomaly cases presenting trisomy 21, osteocraniostenosis syndrome, isolated
      congenital heart defect, and oligohydramnios sequence due to prune belly
      syndrome, in which fusion was observed. This demonstrates that, although it may
      be more common in trisomy 13, this phenomenon should not be interpreted as
      pathognomonic to that syndrome.

PMID- 15255042
TI  - Multiple causes of sexual segregation in European red deer: enlightenments from
      varying breeding phenology at high and low latitude.
AB  - Sexual segregation outside the mating season occurs in most species of sexually
      dimorphic ungulates and has been extensively described in the literature, but the
      mechanisms causing segregation are still debated. The detailed pattern of sexual
      segregation throughout the year has rarely been presented for mammals, and no
      study, to our knowledge, has used latitudinal-related variation in breeding
      phenology to shed light on the underlying mechanisms. Recent methodological
      developments have made it possible to quantify separate components of segregation
      (social, habitat) and activity synchrony in animal groups, but these major
      improvements have so far been little used. We observed European red deer year
      round at two widely different latitudes (France and Norway) and tested three
      different mechanistic hypotheses of segregation related to: (i) predation risk;
      (ii) body-size-related forage selection; and (iii) activity budget. Habitat
      segregation peaked during calving in both populations and dropped rapidly after
      calving. Females with calves were more segregated from males than were females
      without calves, pointing to a key role of antipredator behaviour even though
      large predators are absent in France and extremely rare in Norway. However, at
      both sites individuals also grouped with their own sex within habitat types (i.e.
      social segregation), and individuals in mixed-sex groups were less synchronized
      in activity type than individuals in either unisex male or unisex female groups,
      suggesting that differences in activity budgets are involved. Social segregation
      peaked during calving and was lowest during the rut (indicating aggregation) in
      both populations; these activities occurred one month later in the Northern
      populations, corresponding well with known differences in breeding phenology. We
      conclude that latitude-dependent breeding phenology shapes the seasonal pattern
      of sexual segregation and that sexual segregation in ungulates has multiple
      causes.

PMID- 15255043
TI  - The herring gull complex is not a ring species.
AB  - Under what circumstances speciation in sexually reproducing animals can occur
      without geographical disjunction is still controversial. According to the ring
      species model, a reproductive barrier may arise through 'isolation by distance'
      when peripheral populations of a species meet after expanding around some
      uninhabitable barrier. The classical example of this kind of speciation is the
      herring gull (Larus argentatus) complex, with a circumpolar distribution in the
      Northern Hemisphere. Based on mitochondrial DNA variation among 21 gull taxa, we
      show that members of this complex differentiated largely in allopatry following
      multiple vicariance and long-distance-colonization events, not primarily through
      isolation by distance. Reproductive isolation evolved more rapidly between some
      lineages than between others, irrespective of their genetic distance. Extant taxa
      are the result of divergent as well as reticulate evolution between two ancestral
      lineages originally separated in a North Atlantic refugium and a continental
      Eurasian refugium, respectively. Continental birds expanded along the entire
      north Eurasian coast and via Beringia into North America. Contrary to the ring
      species model, we find no genetic evidence for a closure of the circumpolar ring
      through colonization of Europe by North American herring gulls. However, closure
      of the ring in the opposite direction may be imminent, with lesser black-backed
      gulls about to colonize North America.

PMID- 15255044
TI  - Pythons metabolize prey to fuel the response to feeding.
AB  - We investigated the energy source fuelling the post-feeding metabolic
      upregulation (specific dynamic action, SDA) in pythons (Python regius). Our goal
      was to distinguish between two alternatives: (i) snakes fuel SDA by metabolizing
      energy depots from their tissues; or (ii) snakes fuel SDA by metabolizing their
      prey. To characterize the postprandial response of pythons we used transcutaneous
      ultrasonography to measure organ-size changes and respirometry to record oxygen
      consumption. To discriminate unequivocally between the two hypotheses, we
      enriched mice (= prey) with the stable isotope of carbon (13C). For two weeks
      after feeding we quantified the CO2 exhaled by pythons and determined its
      isotopic 13C/12C signature. Ultrasonography and respirometry showed typical
      postprandial responses in pythons. After feeding, the isotope ratio of the
      exhaled breath changed rapidly to values that characterized enriched mouse
      tissue, followed by a very slow change towards less enriched values over a period
      of two weeks after feeding. We conclude that pythons metabolize their prey to
      fuel SDA. The slowly declining delta13C values indicate that less enriched
      tissues (bone, cartilage and collagen) from the mouse become available after
      several days of digestion.

PMID- 15255045
TI  - Postural role of lateral axial muscles in developing bottlenose dolphins
      (Tursiops truncatus).
AB  - Foetal dolphins (Tursiops truncatus) are bent ventrolaterally, such that the
      tailflukes and lower jaw are juxtaposed. The lateral flexibility required en
      utero may compromise the efficiency of the dorsoventral oscillations required of
      the swimming neonate. The m. intertransversarius caudae dorsalis (IT) is the most
      laterally placed epaxial muscle. Bilateral contractions of the IT could limit
      lateral deformations of the flexible tailstock of the early neonate. We test the
      hypothesis that the IT is functioning as a postural muscle in neonates by
      examining its morphological, histological and biochemical properties. The
      neonatal IT has a relatively large cross-sectional area and bending moment, as
      well as a large proportion of slow-twitch fibres and elevated myoglobin
      concentrations. Our results demonstrate that the IT is functionally capable of
      performing this specific postural function in neonatal dolphins. In later life
      history stages, when postural control is no longer needed, the IT serves to fine
      tune the position of the tailstock during locomotion. The changing function of
      the adult IT is concomitant with changes in morphology and biochemistry, and most
      notably, with an increase in the proportion of fast-twitch fibres. We suggest
      that these changes reflect strong selective pressure to improve locomotor
      abilities by limiting lateral deformations during this critical life-history
      stage.

PMID- 15255046
TI  - Age and size at maturity: sex, environmental variability and developmental
      thresholds.
AB  - In most organisms, transitions between different life-history stages occur later
      and at smaller sizes as growth conditions deteriorate. Day and Rowe recently
      proposed that this pattern could be explained by the existence of developmental
      thresholds (minimum sizes or levels of condition below which transitions are
      unable to proceed). The developmental-threshold model predicts that the reaction
      norm of age and size at maturity will rotate in an anticlockwise manner from
      positive to a shallow negative slope if: (i) initial body size or condition is
      reduced; and/or (ii) some individuals encounter poor growth conditions at
      increasingly early developmental stages. We tested these predictions by rearing
      replicated populations of soil mites Sancassania berlesei (Michael) under
      different growth conditions. High-food environments produced a vertical
      relationship between age and size at maturity. The slope became increasingly
      shallow as food was reduced. By contrast, high food in the maternal environment
      reduced the slope of the reaction norm of age and size at maturity, whereas low
      food increased it. Overall, the reaction norm of age and size at maturity in S.
      berlesei was significantly nonlinear and differed for males and females. We
      describe how growth conditions, mother's environment and sex determine age and
      size at maturity in S. berlesei.

PMID- 15255047
TI  - Costs of immunity: immune responsiveness reduces survival in a vertebrate.
AB  - Immune defences are undoubtedly of great benefit to the host, reducing the impact
      of infectious organisms. However, mounting immune responses also entails costs,
      which may be measured by inducing immune responses against artificial infections.
      We injected common eider (Somateria mollissima) females with three different non
      pathogenic antigens, sheep red blood cells (SRBC), diphtheria toxoid and tetanus
      toxoid, early in their incubation period. In the group of females that mounted a
      humoral immune response against SRBC, the return rate was only 27%, whereas the
      group of females that did not mount a response against SRBC had a return rate of
      72%. Moreover, responding against diphtheria toxoid when also responding against
      SRBC led to a further reduction in return rate. These results are repeatable, as
      the same effect occurred independently in two study years. The severely reduced
      return rate of females producing antibodies against SRBC and diphtheria toxoid
      implies that these birds experienced considerably impaired long-term survival.
      This study thus documents severe costs of mounting humoral immune responses in a
      vertebrate. Such costs may explain why many organisms suppress immunity when
      under stress or when malnourished, and why infections may sometimes be tolerated
      without eliciting immune responses.

PMID- 15255048
TI  - Feedback control of T-cell receptor activation.
AB  - The specificity and sensitivity of T-cell recognition is vital to the immune
      response. Ligand engagement with the T-cell receptor (TCR) results in the
      activation of a complex sequence of signalling events, both on the cell membrane
      and intracellularly. Feedback is an integral part of these signalling pathways,
      yet is often ignored in standard accounts of T-cell signalling. Here we show,
      using a mathematical model, that these feedback loops can explain the ability of
      the TCR to discriminate between ligands with high specificity and sensitivity, as
      well as provide a mechanism for sustained signalling. The model also explains the
      recent counter-intuitive observation that endogenous 'null' ligands can
      significantly enhance T-cell signalling. Finally, the model may provide an
      archetype for receptor switching based on kinase-phosphatase switches, and thus
      be of interest to the wider signalling community.

PMID- 15255049
TI  - Unravelling migrations in the steppe: mitochondrial DNA sequences from ancient
      central Asians.
AB  - This study helps to clarify the debate on the Western and Eastern genetic
      influences in Central Asia. Thirty-six skeletal remains from Kazakhstan (Central
      Asia), excavated from different sites dating between the fifteenth century BC to
      the fifth century AD, have been analysed for the hypervariable control region
      (HVR-I) and haplogroup diagnostic single nucleotide polymorphisms (SNPs) of the
      mitochondrial DNA genome. Standard authentication criteria for ancient DNA
      studies, including multiple extractions, cloning of PCR products and independent
      replication, have been followed. The distribution of east and west Eurasian
      lineages through time in the region is concordant with the available
      archaeological information: prior to the thirteenth-seventh century BC, all
      Kazakh samples belong to European lineages; while later an arrival of east
      Eurasian sequences that coexisted with the previous west Eurasian genetic
      substratum can be detected. The presence of an ancient genetic substratum of
      European origin in West Asia may be related to the discovery of ancient mummies
      with European features in Xinjiang and to the existence of an extinct Indo
      European language, Tocharian. This study demonstrates the usefulness of the
      ancient DNA in unravelling complex patterns of past human migrations so as to
      help decipher the origin of present-day admixed populations.

PMID- 15255050
TI  - A receiver bias in the origin of three-spined stickleback mate choice.
AB  - Receiver-bias models of signal evolution predict that male sexually selected
      traits evolve through prior selection for other functions. Female three-spined
      sticklebacks (Gasterosteus aculeatus) in many populations show a mating
      preference for males with a red throat and jaw. It has been proposed that this
      preference evolved because the choice of males with red coloration confers direct
      and indirect benefits to females in accordance with the Fisher-Zahavi model of
      sexual selection. We present indirect evidence that the preference is an effect
      of a receiver bias in the perceptual or cognitive system of G. aculeatus for the
      colour red, which may have arisen in the context of foraging. In laboratory
      trials, male and female three-spined and nine-spined sticklebacks (Pungitius
      pungitius) responded most strongly to red objects outside a mating context. This
      result demonstrates a correlation between a sexually selected trait and an
      intrinsic attraction to red objects, and supports the sensory-exploitation model
      for the evolution of red nuptial coloration in three-spined sticklebacks.

PMID- 15255051
TI  - Nine-spined sticklebacks exploit the most reliable source when public and private
      information conflict.
AB  - Social foragers can potentially use private information gained from personal
      experience and public information gained from observing the foraging success of
      others to determine the profitability of a foraging patch. We investigated how
      nine-spined sticklebacks use conflicting public and private information of
      variable reliability to make foraging decisions. In a first experiment, when
      private information was reliable, sticklebacks ignored public information and
      based their foraging decision on private information. However, when private
      information was less reliable, sticklebacks tended to use public rather than
      private information. A second experiment investigated how the time since
      experiencing private information affected sticklebacks' use of this information
      when it conflicted with recent public information. Fish based their foraging
      decisions on recently acquired private information, but reliance on private
      information diminished as the period since experiencing it increased. Fish used
      public information if 7 days had elapsed since updating their private
      information. Our findings suggest that nine-spined sticklebacks flexibly adjust
      their decision making to exploit the most reliable information available, be it
      public or private, and that animals will weight private and public information
      appropriately depending on circumstances.

PMID- 15255052
TI  - Experimental evidence that kin discrimination in the Seychelles warbler is based
      on association and not on genetic relatedness.
AB  - In cooperative breeding systems driven by kin selection, effective kin
      recognition cues are important. Recognition could be achieved by the direct
      assessment of the genetic relatedness of individuals or by learning through
      association. In the Seychelles warbler, Acrocephalus sechellensis, female
      subordinates maximize indirect fitness by preferentially helping genetically
      related nestlings. Help seems to be based on the continued presence of the
      primary female who previously fed the subordinate in the nest but it has, so far,
      been impossible to discount the direct assessment of genetic relatedness. We used
      a cross-fostering experiment to separate the two possible cues. Adult birds did
      not discriminate between their own and cross-fostered eggs or nestlings. Cross
      fostering resulted in nestlings that were unrelated to the primary female that
      raised them, but control nestlings were closely related to their primary females.
      The proportions of cross-fostered and control female offspring that stayed and
      became helpers on their 'natal' territory were similar. However, for both groups
      the chance of becoming a subordinate helper was associated with the continued
      presence of the primary female and not with any other factor tested. Our study
      provides strong evidence that helping decisions are based on associative-learning
      cues.

PMID- 15255053
TI  - The influence of contests on optimal clutch size: a game-theoretic model.
AB  - We develop a game-theoretic model to predict the effect of size-dependent contest
      outcomes on optimal-clutch-size decisions. We consider the case where larger
      individuals develop from smaller clutches and, as adults, are advantaged in
      competition for limiting resources. The relationship between fitness and size
      thus depends on the sizes of other members of the population. We show that clutch
      size optima are decreased by body-size-dependent contest outcomes, with larger
      effects when body size is most affected by clutch size, when prior resource
      ownership has less influence on contest outcome and when contests occur more
      frequently. We also show the existence of polymorphisms in clutch-size optima and
      that clutch-size driven changes in population density can, via an effect on the
      probability of host finding, further influence optimal clutch size. Our model is
      formulated to match the life history of a parasitoid wasp, in which clutch size
      affects offspring size and females engage in direct contests for host ownership,
      which larger females tend to win; we confirm that female-female competition is
      likely to influence clutch size in this species. However, the model is also
      relevant to clutch size in other taxa and supports recent suggestions concerning
      reproductive decisions in great tits.

PMID- 15255054
TI  - The role of male disease susceptibility in the evolution of haplodiploid insect
      societies.
AB  - Heterozygosity at loci affecting resistance against parasites can benefit host
      fitness. We predict that, in haplodiploid species, haploid males will suffer
      decreased parasite resistance relative to diploid females. We suggest that
      elevated susceptibility in haploid males has shaped the evolution of social
      behaviour in haplodiploid species. Male susceptibility will select for
      behavioural adaptations that limit males' exposure to pathogens and that limit
      male transmission of pathogens within and between colonies. The relatedness
      asymmetry hypothesis that has been advanced to explain female-only workers does
      not make these predictions. We review the relevant evidence for genetic effects
      on parasite resistance in insects and summarize empirical evidence that relates
      to the haploid-susceptibility hypothesis.

PMID- 15255055
TI  - Palaeoecology and palaeophytogeography of the rhynie chert plants: evidence from
      integrated analysis of in situ and dispersed spores.
AB  - The Rhynie cherts yield exceptionally preserved early land plants, and provide a
      unique insight into the nature of Lower Devonian vegetation. Hitherto they have
      been poorly age constrained, and the palaeoecology and palaeophytogeography of
      the flora are poorly understood. Well-preserved dispersed-spore assemblages have
      been recovered from a number of borehole cores through the stratigraphical
      sequence of the Rhynie outlier. They are all similar and belong with the
      polygonalis-emsiensis (PE) spore zone, indicating an Early Devonian age (Early
      (but not earliest) Pragian to earliest Emsian). Comparisons with PE spore-zone
      assemblages from elsewhere suggest that the flora of the Rhynie drainage basin
      was slightly impoverished, with certain plant taxa that occurred at other
      locations not represented. This probably reflects differences between the flora
      of an inland intermontaine basin (Rhynie) and that of the lowland flood-plains.
      In situ spores have been characterized for all seven Rhynie chert plants.
      Analysis of the distribution of these spore types in the Rhynie sequence, in
      addition to those of coeval deposits from elsewhere, enables interpretation of
      the palaeoecology and palaeophytogeography of the Rhynie chert plants. It is
      concluded that at least some of the plants were not highly specialized or adapted
      to the peculiar hot-springs environment in which they are preserved. Rather, they
      were components of a diverse and widespread flora, but were the only elements
      able to tolerate the inhospitable hot-springs environment (i.e. they were
      preadapted).

PMID- 15255056
TI  - Long-term care under fire: a case for rational enforcement.
AB  - Despite reforms to ensure that nursing homes maintain compliance with federal
      quality standards, one-fourth of all homes nationwide continue to be cited for
      deficiencies that either caused actual harm to residents or carried the potential
      for death or serious injury. This pattern has not changed since the July 1995
      reforms were implemented. Although the reforms equipped federal and state
      regulators with many alternatives and tools to help promote sustained compliance
      with Medicare and Medicaid standards, the way in which states and HCFA have
      applied them appears to have resulted in little headway against the pattern of
      serious and repeated noncompliance. Such performance may do little to dispel
      concerns over the health and safety of frail and dependent nursing home
      residents.

PMID- 15255057
TI  - Tough love: the emergence of criminal statutes and disciplinary actions against
      managed care plans for inadequate care.

PMID- 15255058
TI  - Federal funding of human embryonic stem cell research--illegal, unethical and
      unnecessary.

PMID- 15255060
TI  - Tomorrow's unleaded children: child care facilities, lead paint and the law.

PMID- 15255059
TI  - A case for federal funding of human embryonic stem cell research: the interplay
      of moral absolutism and scientific research.

PMID- 15255061
TI  - The fox guarding the henhouse: how the Health Care Quality Improvement Act of
      1986 and State peer review protection statutes have helped protect bad faith peer
      review in the medical community.

PMID- 15255062
TI  - To tell or not to tell: the scope of physician-patient confidentiality when
      relatives are at risk of genetic disease.

PMID- 15255063
TI  - Fitting a square peg in a round hole: why traditional tort principles do not
      apply to wrongful birth actions.

PMID- 15255064
TI  - Circumventing environmental policy: does the Americans with Disabilities Act
      provide protection where environmental statutes don't?

PMID- 15255065
TI  - The jurisprudence of public health: reflections on Lawrence O. Gostin's public
      health law.

PMID- 15255066
TI  - Direct actions of leptin on bone remodeling.

PMID- 15255067
TI  - Effect of age, weight and lifestyle factors on calcaneal quantitative ultrasound
      in premenopausal women: the ESOPO study.
AB  - The objective of this study was to identify the determinants of bone mass as
      measured by quantitative ultrasound (QUS) in premenopausal women. The study
      population is part of the "Epidemiological Study On the Prevalence of
      Osteoporosis" (ESOPO) on risk of the general population of Italy. We report the
      data on 2727 premenopausal women aged 40-50 years who are still regularly
      menstruating. Bone stiffness (called simplicity stiffness), which is derived from
      the values of broadband ultrasound attenuation (BUA) and speed of sound (SoS),
      was measured by a heel QUS device (Achilles Apparatus, Lunar, Co. USA). The most
      commonly recognized determinants of bone mass were modelled with stiffness by
      multiple regression analysis or analysis of variance (ANOVA). Bone stiffness was
      negatively related to age and number of cigarettes and positively to body weight,
      body weight at 25 years, height and estimated daily calcium intake. By multiple
      regression analysis, independent, positive, predictors of bone stiffness were
      age, weight at 25 years and daily calcium intake. Bone stiffness adjusted for age
      and body weight at 25 years was positively associated with outdoor activity score
      and negatively with number of pregnancies, chronic use of any drug, smoking and
      subjective health status. Bone stiffness was also somewhat (p < 0.015) negatively
      related to history of prolonged bedrest and thyroxin use. In conclusion, our
      results indicate that risk factors usually associated in other studies with DXA
      BMD in elderly women are also associated with calcaneal bone stiffness, as
      measured by QUS in premenopausal women. These findings should help to identify
      premenopausal women at risk and to design an early strategy for osteoporosis
      prevention based on eliminating modifiable risks.

PMID- 15255068
TI  - Insulin-like growth factor I is a determinant of hip bone mineral density in men
      less than 60 years of age: MINOS study.
AB  - Several studies show that in elderly men bone mineral density (BMD) is not
      correlated with the insulin-like growth factor (IGF-I) level, but data are scanty
      in young men. Results of studies correlating insulin-like growth factor binding
      protein 3 (IGFBP-3) and BMD in men are discordant. As different hypotheses can
      explain the discordant results, we evaluated the correlation of BMD with serum
      IGF-I, IGFBP-3, and IGF-I/IGFBP-3 index in a large cohort of 721 men aged 19-85
      years taking into account age, body weight, 17beta-estradiol, free testosterone,
      and parathyroid hormone. Serum IGF-I and IGFBP-3 decreased with age (r = -0.44
      and r = -0.36, P = 0.0001). After adjustment for confounding variables, IGF-I
      correlated weakly positively with BMD and with bone mineral apparent density
      (BMAD) of hip as well as with cortical thickness of femoral neck, both of which
      are determined mainly by bone resorption, but not with bone size determined by
      periosteal apposition. IGF-I correlated weakly positively with BMD at the whole
      body and at the third lumbar vertebra IGFBP-3 and IGF-I/IGFBP-3 index did not
      correlate with densitometric parameters. In men aged 19-60 years, IGF-I
      correlated with BMD and BMAD of total hip and with cortical thickness of femoral
      neck positively and more strongly than in the entire cohort but not with the size
      of proximal femur. BMD of total hip was 6% higher in men in the highest quartile
      of IGF-I than in men in the lowest quartile. IGF-I, IGFBP-3, and IGF-I/IGFBP-3
      index did not correlate with densitometric parameters of other sites. In the men
      aged more than 60 years, neither IGF-I nor IGFBP-3 nor IGF-I/IGFBP-3 index
      correlated with BMD, BMAD, or bone size. In men aged 19-60 years, the most
      significant hormonal determinants of BMD and BMAD of the hip and of the cortical
      thickness of femoral neck were 17beta-estradiol and IGF-I (P < 0.05-0.0001). In
      men aged more than 60 years, the most significant determinants of hip BMD were
      17beta-estradiol and PTH. In conclusion, IGF-I seems to contribute to the
      inhibition of bone resorption and to maintaining bone mass of the proximal femur
      during the phase of slow bone loss in men aged less than 60 years. IGFBP-3 and
      IGF-I/IGFBP-3 index were not correlated with BMD or bone size.

PMID- 15255069
TI  - Effects of potassium citrate supplementation on bone metabolism.
AB  - Western diets rich in animal protein result in long-term acid loading that,
      despite corresponding increases in net renal acid excretion, may induce a chronic
      state of acidemia. This may have deleterious effects on both the kidney and bone,
      by increasing the risk of calcium stone in the former and leading to chemical
      dissolution of mineral alkaline salts in the latter. Whereas supplementation with
      alkaline citrate has been shown to reduce stone recurrences, its effect on bone
      turnover has received less attention. The aim of the present study was to
      evaluate whether potassium citrate favorably affects bone turnover markers in
      postmenopausal females with low bone density. Thirty women, aged 58 +/- 8.1
      years, were enrolled and studied on basal conditions and after a 3-month course
      of potassium citrate supplementation (0.08-0.1 g/kg b.w. daily). Twenty-two women
      concluded the study while 8 withdrew. Twenty-four age-matched healthy women were
      taken as control cases. All were evaluated for electrolyte and acid-base balance
      related parameters, bone turnover, markers and renal function. A significant
      decrease in net acid excretion was observed upon citrate supplementation, and
      this was paralleled by a significant decrease of urinary deoxypyridinolines,
      hydroxyproline-to-creatinine ratios, and, to a lesser extent, serum osteocalcin.
      Percent variations of urine citrate were inversely related to those of
      deoxypyridinolines and hydroxyproline. No change in these chemistries occurred in
      the control group. Our results suggest that treatment with an alkaline salt, such
      as potassium citrate, can reduce bone resorption thereby contrasting the
      potential adverse effects caused by chronic acidemia of protein-rich diets.

PMID- 15255070
TI  - Variability of collagen crosslinks: impact of sample collection period.
AB  - Because of the variability of collagen crosslinks, their use as markers for bone
      resorption is often criticized. We hypothesized that the variability could be
      reduced by collecting urine for 24 hours (or longer) instead of using single
      voids, and by not normalizing to creatinine. Urine samples were collected from 22
      healthy subjects during two or more 24-hour periods. Each 24-hour pool and each
      2nd void of the day were analyzed for N-telopeptide (NTX), pyridinium (PYD), and
      deoxypyridinoline (DPD) crosslinks. Data were analyzed by using linear
      regression. For NTX, R2 for the two, 2nd-void samples (n = 38) was 0.55, whereas
      R2 for the two 24-hour pools was 0.51 or 0.52, expressed per day or per
      creatinine. For PYD and DPD, R2 for the 2nd-void samples was 0.26 and 0.18, R2
      for the 24-hour pools expressed per day was 0.58 and 0.74, and R2 for the 24-hour
      pools expressed per creatinine was 0.65 and 0.76, respectively. Regression of the
      2nd void and the corresponding 24-hour pool, expressed per day, yielded R2 =
      0.19, 0.19, and 0.08, for NTX, PYD, and DPD, respectively (n = 76 each). For the
      2nd-void sample and its corresponding 24-hour pool, expressed per creatinine, R2
      = 0.24, 0.33, and 0.08, respectively. In a separate study, the coefficient of
      variation for NTX was reduced (P < 0.05) when data from more than one 24-hour
      collection were combined. Thus, the variability inherent in crosslink
      determinations can be reduced by collecting urine for longer periods. In research
      studies, the high variability of single-void collections, compounded by
      creatinine normalization, may alter or obscure findings.

PMID- 15255071
TI  - Digital radiogrammetry of the hand in a pediatric and adolescent Dutch Caucasian
      population: normative data and measurements in children with inflammatory bowel
      disease and juvenile chronic arthritis.
AB  - We have evaluated the applicability of a new Digital X-ray Radiogrammetry (DXR)
      system in a Dutch Caucasian pediatric population. For this study we enrolled 535
      healthy participants who all signed an informed consent form. In addition, 20
      children suffering from inflammatory bowel disease (IBD) and juvenile chronic
      arthritis (JCA) were enrolled. Radiographs of the left hand were obtained from
      all participants. From the healthy population a subset of children with a history
      of forearm fractures were separately analyzed. Measurements consisted of DXR (X
      posure; Pronosco-Sectra, Linkoping, Sweden). Five hundred thirty-five subjects
      were enrolled in the study. Twenty-two subjects (4.3%) were discontinued (age 3
      10 years), all because of a nonrecognizable radiograph by the DXR system. The
      short-term coefficient of variation of DXR in this population was 0.59%.
      Significant differences in DXR-BMD between boys and girls for the ages of 11, 12,
      16, 17, and 18 years were found. There were also significant differences in DXR
      BMD between the sequential Tanner stages. For 88 subjects repeat radiographs were
      available (mean interval 1.8 years). In all cases an increase in DXR-BMD was
      seen. Girls with IBD, JCA, or a history of forearm fractures and boys with IBD
      showed a significantly lower DXR-BMD compared with healthy controls. We show that
      DXR is an applicable technique in children. Also, in a small subpopulation it is
      possible to discriminate children with a high risk of low BMD.

PMID- 15255072
TI  - Treatment with parathyroid hormone hPTH(1-34), hPTH(1-31), and monocyclic hPTH(1
      31) enhances fracture strength and callus amount after withdrawal fracture
      strength and callus mechanical quality continue to increase.
AB  - The influence of intermittent hPTH(1-34)NH2, hPTH(1-31)NH2, and monocyclic
      [Leu27]cyclo (Glu22-Lys26)hPTH(1-31)NH2 treatment on callus formation, mechanical
      strength, and callus tissue mechanical quality of tibial fractures in rats was
      investigated after 8 and 16 weeks of healing. In the 8 weeks of healing animals,
      the PTH-peptides were injected subcutaneously during the entire observation
      period (15 nmol/kg/day [hPTH(1-34)NH2: 15 nmol = 60 microg]), and control animals
      with fractures were given vehicle. In the 16 weeks of healing animals, the PTH
      peptides were injected only during the first 8 weeks of healing (15 nmol/kg/day),
      after which the animals were left untreated during the rest of the healing
      period. After the first 8 weeks of healing, increased fracture strength and
      callus volume were seen in the PTH-treated rats (ultimate load 66%, ultimate
      stiffness 58%, callus volume 28%), and the three peptides were equally effective.
      No difference in callus tissue mechanical quality was found between PTH and
      vehicle animals. After 16 weeks of healing, no differences in fracture strength,
      callus volume, or callus tissue mechanical quality were seen between PTH and
      vehicle. When comparing PTH-treated animals at 8 and 16 weeks, fracture strength
      and callus tissue mechanical quality continued to increase after the withdrawal
      of PTH (ultimate load 23%, ultimate stress 88%, elastic modulus 87%) and external
      callus volume declined during this period (27%).

PMID- 15255073
TI  - Discriminative capacity of calcaneal quantitative ultrasound and of osteoporosis
      and fracture risk factors in postmenopausal women with osteoporotic fractures.
AB  - Bone fragility fractures constitute the principal complication of osteoporosis.
      The identification of individuals at high risk of sustaining osteoporotic
      fractures is important for implementing preventive measures. The purpose of this
      study is to analyze the discriminative capacity of a series of osteoporosis and
      fracture risk factors, and of calcaneal quantitative ultrasound (QUS), in a
      population of postmenopausal women with a history of osteoporotic fracture. A
      cross-sectional analysis was made of a cohort of 5195 women aged 65 or older
      (mean +/- SD: 72.3 +/- 5.4 years) seen in 58 primary care centers in Spain. A
      total of 1042 women (20.1%) presented with a history of osteoporotic fracture.
      Most fractures (93%) were non-vertebral. Age-adjusted odds ratios corresponding
      to each decrease in one standard deviation of the different QUS parameters ranged
      from 1.47 to 1.55 (P < 0.001) for fractures. The age-adjusted multivariate
      analysis yielded the following risk factors independently associated with a
      history of osteoporotic fracture: number of fertile years, a family history of
      fracture, falls in the previous year, a history of chronic obstructive airway
      disease, the use of antiarrhythmic drugs, and a low value for any of the QUS
      parameters. The area under the receiver operating characteristic curve of the
      best model was 0.656. In summary, a series of easily assessable osteoporotic
      fracture risk factors has been identified. QUS was shown to discriminate between
      women with and without a history of fracture, and constitutes a useful tool for
      assessing fracture risk. Various of the vertebral and hip fracture risk factors
      frequently cited in North American and British populations showed no
      discriminative capacity in our series--thus suggesting that such factors may not
      be fully applicable to our population and/or to the predominant type of fractures
      included in the present study.

PMID- 15255074
TI  - Nucleobindin--a Ca2+-binding protein present in the cells and mineralized tissues
      of the tooth.
AB  - Nucleobindin, a Ca2+-binding protein, has been previously identified within the
      nucleus and endoplasmic reticulum, and in association with the Golgi membrane. In
      addition, nucleobindin has been shown to be a minor constituent of bone
      extracellular matrix and has been postulated to play a role in mineralization. In
      the current investigation, we report the expression and localization of
      nucleobindin within odontoblasts and the dentin matrix. Nucleobindin mRNA
      transcripts were detected in the tooth, and in situ hybridization analysis
      substantiated the findings, showing nucleobindin expression within mature
      odontoblasts and within the cells of surrounding developing alveolar bone.
      Western blot analysis of tooth protein extracts demonstrated the presence of a 63
      kDa protein, which showed immunologic affinity for a rat nucleobindin peptide
      antibody. The distribution of the protein was shown in mature odontoblasts by
      using immunohistochemistry. Moreover, immunogold labeling of nucleobindin and
      subsequent ultrastructural analysis demonstrated a similar pattern of
      distribution. Nucleobindin was identified within odontoblast cellular
      compartments: the nucleus, endoplasmic reticulum, and mitochondria. Of interest,
      nucleobindin localization was observed within the surrounding dentin
      extracellular matrix, and immunogold labeling was shown to accumulate with tissue
      development toward the cusp. The study clearly demonstrated the presence of
      nucleobindin within dental tissues. In consideration of the known functional
      properties of nucleobindin, it may be postulated that nucleobindin may contribute
      to the accumulation and transport of Ca2+ ions to the mineralization front prior
      to hydroxyapatite deposition.

PMID- 15255075
TI  - Diminished acute response of osteoclasts to calcium load in thyroidectomized
      patients.
AB  - To elucidate the role of endogenous calcitonin (CT) in the regulation of bone
      resorption, we evaluated the acute effects of an intravenous calcium load in nine
      patients after total thyroidectomy (aged 29.2 +/- 8 years) compared with nine
      healthy subjects. After overnight fasting, intravenous infusions of elemental
      calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples
      for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid
      hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide
      (beta-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes
      after the start of the infusion. At baseline, parameters of calcium and bone
      metabolism were similar in both groups. A similar increase in S-iCa and decrease
      in plasma PTH levels were observed in both groups. However, the plasma CT
      increased significantly by 13 minutes (P < 0.05) and beta-CTX decreased
      significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with
      the baseline) only in the group consisting of healthy individuals. In the
      thyroidectomized group, the plasma beta-CTX did not decrease significantly during
      the first 60 minutes (decrease by only 8% as compared with the baseline) and
      response to the calcium load was significantly diminished throughout the study
      period as compared with that of the healthy subjects (P < 0.01). In conclusion,
      the results indicate that the increased CT secretion is responsible for the rapid
      initial decrease in the bone resorption following an acute intravenous calcium
      load.

PMID- 15255076
TI  - Triiodothyronine (T3) and 1,25-dihydroxyvitamin D3 (1,25D3) inversely regulate
      OPG gene expression in dependence of the osteoblastic phenotype.
AB  - Both thyroid hormones and 1,25-dihydroxyvitamin D3 (1,25D3) are essential for
      normal development and maintenance of the skeleton. They regulate osteoblastic
      differentiation by influencing expression of osteoblast specific genes like
      osteocalcin (OCN). Mice deficient in OCN, the most abundant noncollagenous
      protein of the bone matrix, develop a phenotype characterized by higher bone mass
      and bone of improved quality. Osteoprotegerin (OPG), another protein important
      for bone metabolism, protects bone and is a regulator of the osteoclast
      development. 1,25D3 down regulates the basal expression of these two proteins in
      osteoblasts and osteoblast-like cells. The involvement of these hormones and
      proteins in the bone metabolism guided us to compare their regulation in cell
      lines with different osteoblastic phenotypes. We found that T3 increased OCN mRNA
      levels in MC3T3-E1 osteoblastic cells independent from their phenotype albeit
      with different potency but not in the bone marrow-derived stromal cell line ST2.
      OPG mRNA expression levels were only stimulated by T3 in mature MC3T3-E1 cells,
      which have the capacity to mineralize, but not in pre-osteoblastic MC3T3-E1 cells
      or in ST2 cells. In the mineralizing osteoblastic cells 1,25D3 inhibited T3
      induced expression for OPG mRNA but not OCN mRNA. In the pre-osteoblastic cell
      line with undetectable OPG mRNA levels, either basal or T3-stimulated, 1,25D3
      inhibited OCN mRNA expression completely. Our results emphasize the importance of
      balanced regulation of mRNA transcript levels for OPG and OCN, by both hormones
      and probably other systemic factors to enable a fine-tuning of bone metabolism at
      specific skeletal sites.

PMID- 15255078
TI  - Systemic amyloidosis: are we moving ahead?
AB  - Systemic amyloidoses are a wide group of diseases with different courses,
      treatments and prognoses. Unequivocal typing of amyloid deposits is important for
      correct diagnosis and appropriate treatment. At present, the most effective
      therapeutic approach is based on eliminating the supply of amyloidogenic
      precursor. New effective therapies will stem from our improved knowledge of the
      molecular mechanisms of amyloidosis.

PMID- 15255077
TI  - Quantification, localization, and expression of IGF-I and TGF-beta1 during growth
      factor-stimulated fracture healing.
AB  - Because of the increasing interest on stimulating fracture healing, knowledge
      about the role and chronology of growth factors during the healing process is
      important. The purpose of this study was to quantify the protein concentration of
      IGF-I and TGF-beta1 during rat tibial fracture healing 5, 10, and 15 days after
      fracture using ELISA methods and to analyze the distribution of the proteins and
      the related mRNA expression in the fracture callus by immunohistochemistry and in
      situ hybridization. The following three groups were analyzed: Fractured tibiae
      intramedullary stabilized with K-wires coated with IGF-I and TGF-beta1 compared
      with fractures stabilized with uncoated K-wires and unfractured tibiae. The
      weight of the callus increased during the healing process in both experimental
      groups. The protein concentration of IGF-I and TGF-beta1 in the fracture callus
      showed significant changes between the investigated time points and treatment
      groups compared with the unfractured tibia. IGF-I increased with healing time
      whereas TGF-beta1 revealed a constantly elevated level at the investigated time
      points. Mesenchymal cells, osteoblasts, osteocytes, proliferating and immature
      chondrocytes, and osteoclasts expressed both growth factors. No differences in
      the expression and localization pattern of the growth factors were detectable
      among the groups. Using the different methods for quantification and
      visualization of the growth factors, no differences (except the increased IGF-I
      concentration at day 15 in the growth factor group) were seen between the normal
      and the growth factor-stimulated fracture healing as an indication for
      physiological healing after exogenous growth factor treatment.

PMID- 15255079
TI  - Therapeutic options in systemic AL amyloidosis.
AB  - Systemic amyloid light chain (AL) amyloidosis is a severe disease with
      unfavourable prognosis. Since the late 1970s different therapeutic modalities in
      AL amyloidosis have been investigated, trying to prolong survival. This review
      deals with the therapeutic modalities in AL amyloidosis to date, and highlights
      future perspectives.

PMID- 15255080
TI  - Diagnosis and treatment of levothyroxine pseudomalabsorption.
AB  - Many causes of malabsorption of levothyroxine in patients with hypothyroidism
      have been thoroughly described in literature. Pseudomalabsorption, poor
      compliance of the patient with the therapy regime, is the most common cause of
      failure of levothyroxine therapy. Pseudomalabsorption is characterised by a
      deficient diagnostic process, patient denial and difficulties in treatment. The
      present article provides guidelines in diagnosing and treating
      pseudomalabsorption in hypothyroidism.

PMID- 15255081
TI  - Two patients with recurrent fever and wine red discolouration of the eyelids.

PMID- 15255082
TI  - Diagnostic and therapeutic approach of systemic amyloidosis.
AB  - Amyloidosis is a group of diseases, all characterised by deposition of protein
      fibrils with a beta-sheet structure. This structure generates affinity of amyloid
      for Congo red dye and is resistant to proteolysis. Three types of systemic
      amyloidosis are important for the clinician: AA (related to underlying chronic
      inflammation), AL (related to underlying monoclonal light chain production) and
      ATTR amyloidosis (related to old age or underlying hereditary mutations of
      transthyretin). Signs and symptoms vary considerably among the three types and
      the choice of treatment differs completely. A stepwise approach in diagnosis and
      therapy is presented. When amyloidosis is suspected the first step is
      histological proof of amyloid and the second is proof of systemic involvement.
      The next two steps are determination of the type of amyloid followed by detection
      of the precursor protein. The fifth step is a thoughtful clinical evaluation,
      necessary for assessment of prognosis and therapy. Subsequently, the choice of
      therapy is based on the 'precursor-product' concept. In the final step, the
      effects of therapy on the underlying disease as well as on the amyloidosis are
      assessed during follow-up. In this evaluation serum amyloid P component (SAP)
      scintigraphy helps to show organ involvement and therapy response.

PMID- 15255083
TI  - Gluconeogenesis and fasting in cerebral malaria.
AB  - BACKGROUND: In healthy subjects after an overnight fast, glucose production is
      for approximately 50% derived from glycogenolysis. If the fast is prolonged,
      glucose production decreases due to a decline in glycogenolysis, while
      gluconeogenesis remains stable. In cerebral malaria, glucose production is
      completely derived from gluconeogenesis after an overnight fast. It is not known
      if glucose production also decreases during fasting when its only source is
      gluconeogenesis. DESIGN: Glucose production was measured by infusion of [6,6
      2H2]glucose in seven patients with cerebral malaria after prolonging a fast from
      20.30 to 00.30 hours. RESULTS: Glucose production decreased by approximately 10%
      (27.4 +/- 2.1 to 24.7 +/- 1.6 micromol/kg/min, p = 0.05), without changes in the
      plasma concentrations of glucoregulatory hormones, FFA or precursors.
      CONCLUSIONS: In the patients with cerebral malaria, glucose production decreases
      during fasting due to a decrease in the rate of gluconeogenesis. These data
      suggest that the decrease in the rate of glucose production during short-term
      fasting is actively regulated and not simply due to shrinkage of glycogen
      content, as in the absence of glycogenolysis, glucose production decreases at the
      same rate as normally seen in healthy subjects whose glucose production is for
      approximately 50% derived from glycogen and in whom gluconeogenesis is stable.

PMID- 15255084
TI  - Meningococcal pericarditis and tamponade.
AB  - We report the case of a 37-year-old female with a complex manifestation of
      serogroup C meningococcal disease. The patient presented with symptoms and signs
      of pneumonia, sepsis and diffuse intravascular coagulation. Moreover, she
      suffered from a culture-proven pyogenic pericarditis that deteriorated into
      cardiac tamponade. Immediate pericardiocentesis was successful and eventually the
      patient recovered.

PMID- 15255085
TI  - Deep vein thrombosis associated with distension of the urinary bladder due to
      benign prostatic hypertrophy--a case report.
AB  - A 76-year-old man was admitted with a first episode of deep vein thrombosis (DVT)
      of his left leg. It was associated with a distended urinary bladder, due to
      benign prostatic hypertrophy. Screening for malignancy was negative. Laboratory
      testing revealed protein S deficiency. Although a distended bladder may induce
      venous stasis, it is not a proven risk factor for DVT. Clinical expression
      possibly depends on the concomitance of other risk factors, such as inherited or
      acquired thrombophilic defects. However, it is also possible that the association
      of a distended bladder with DVT of a lower limb has not been recognised yet. As a
      distended bladder is rather common in elderly men, a proper study is warranted to
      estimate the prevalence of associated DVT.

PMID- 15255086
TI  - What is prescription labeling communicating to doctors about hepatotoxic drugs? A
      study of FDA approved product labeling.
AB  - PURPOSE: The objective of this study was to evaluate the informativeness and
      consistency of product labeling of hepatotoxic drugs marketed in the United
      States. METHODS: We searched the Physicians' Desk Reference-2000 for prescription
      drugs with hepatic failure and/or hepatic necrosis listed in the labeling. We
      used a six-item checklist to evaluate the 'informativeness' and consistency of
      the labeling content. An informativeness score equaled the proportion of
      checklist items present in each drug's labeling. RESULTS: Ninety-five
      prescription drugs were included in the study. Eleven (12%) of the drugs had
      information related to hepatic failure in a Black Boxed Warning, 52 (54%) in the
      Warnings section and 32 (34%) in the Adverse Reactions section of the label. The
      mean informativeness score was 35%; the score was significantly higher, 61%, when
      the risk was perceived to be high. The informativeness of labeling was not
      affected by the time of the labeling, but differed across the Center for Drug
      Evaluation and Research (CDER) Review Division responsible for the labeling.
      CONCLUSIONS: The information provided in labeling is variable and affected by
      many factors, including the perceived level of risk and review division strategy.
      Product labeling may benefit from current FDA initiatives to improve the
      consistency of risk-related labeling.

PMID- 15255087
TI  - Potential savings from increased use of generic drugs in the elderly: what the
      experience of Medicaid and other insurance programs means for a Medicare drug
      benefit.
AB  - BACKGROUND: Generic medications provide the same clinical effect at lower cost
      than brand name drugs but little is known about the extent to which such savings
      are achieved in drug benefit programs serving the elderly. METHODS: Using patient
      level claims data for participants aged 65 or more in one state Medicaid program
      and in a non-Medicaid drug insurance program for the elderly, we compared the
      expenditures in each program for brand name prescriptions with the amount that
      would have been paid for generic versions of the same agents. We then estimated
      potential savings from increased use of substitutable brand name drugs. RESULTS:
      There was an unrealized annual savings of 3.4 million dollars (3.6% of total drug
      expenditure) in the Medicaid program studied and 13.7 million dollars (9.5% of
      total drug expenditure) in the non-Medicaid drug insurance program for the
      elderly, with corresponding reductions in mean annual per-patient drug costs.
      CONCLUSIONS: More widespread use of generic medications represents an important
      source of unrealized savings in drug coverage programs for the elderly. The
      Medicaid program limits the excess spending on brand name drugs by imposing
      pricing restrictions, but many non-Medicaid programs could realize even larger
      savings from reducing the use of brand name drugs when identical generic products
      are available. These findings offer some insight into the potential expense of a
      Medicare prescription drug benefit.

PMID- 15255088
TI  - Defining hormone replacement therapy in longitudinal studies: impact on measures
      of effect.
AB  - Data from a nested case-control study, designed to examine the effect of hormone
      replacement therapy (HRT) on colorectal cancer risk, were analyzed to determine
      the effect of exposure definition on the estimation of risk ratios (RR). A
      prescription drug plan database was used to ascertain HRT prescriptions dispensed
      prior to index dates to cases (n = 3059) and age-matched controls (n = 12,116).
      HRT exposure was defined as 'prescription' and 'tablet' counts, 'conjugated
      estrogen only' and a method based on proportions of minimum exposure to a number
      of estrogens (SUM-P3 and SUM-P12). The effect of HRT was described with reference
      to 'ever', <5 and > or = 5 years of HRT use. Conditional logistic regression was
      used to estimate ORs and 95% confidence intervals (CI). Adjusted ORs for 'ever
      use' of HRT ranged from 0.72 (95%CI: 0.60-0.88) to 0.86 (95%CI: 0.76-0.99); for
      <5 years use, from 0.70 (95%CI: 0.56-0.88) to 0.89 (95%CI: 0.78-1.01) and for >5
      year of HRT use, from 0.74 (95%CI: 0.59-0.92) to 0.98 (95%CI: 0.42-2.26). Various
      methods used to define HRT exposure produce a range of estimated ORs that vary in
      magnitude similar to results reported in the literature from observational
      studies investigating the association between HRT and colorectal cancer.

PMID- 15255089
TI  - Health outcomes among patients receiving oseltamivir.
AB  - PURPOSE: Oseltamivir was approved by the FDA for the treatment of influenza in
      1999. The primary objective was to compare health outcomes among influenza
      patients who were treated with oseltamivir and those who were not. METHODS: The
      patient population included UnitedHealthcare members who received an influenza
      diagnosis during the 1999-2000 influenza season, divided into those who were
      dispensed oseltamivir on the same day (N = 3211) and those who were not dispensed
      oseltamivir (N = 19,985). Cardiovascular, neuropsychiatric and respiratory
      outcomes were assessed from medical claims for a 30-day period. RESULTS: The
      adjusted incidence rate ratio for major cardiac outcome was 0.56 (95%CI: 0.34
      0.93) in those without a positive history of major cardiac disease, indicating
      that those in the oseltamivir group tended to be at lower risk of cardiac
      outcomes than those without oseltamivir. The adjusted incidence rate ratio for
      major neuropsychiatric outcome was 0.72 (95%CI: 0.53-0.97) in the negative
      history of neuropsychiatric disease stratum. The incidence rate ratios for
      respiratory events were more variable. CONCLUSIONS: There appears to be no
      increased risk of cardiac or neuropsychiatric outcomes among subjects with
      influenza who were treated with oseltamivir in comparison with those who were
      not.

PMID- 15255090
TI  - Physician adherence to recommendations for duration of empiric antibiotic
      treatment for uncomplicated urinary tract infection in women: a national drug
      utilization analysis.
AB  - BACKGROUND: Current guidelines for the empiric treatment of uncomplicated urinary
      tract infection in women recommend that first-line trimethoprim-sulfamethoxazole
      (TMP-SMX) or ofloxacin be given for 3 days and nitrofurantoin for 5 days.
      Increasing the duration of treatment raises costs, and perhaps, the incidence of
      adverse effects, without contributing to effectiveness. The aim of this study was
      to investigate physician adherence to these recommendations. METHODS: The
      electronic patients record system of a nationwide health management organization
      in Israel was reviewed for all primary care visits by adult women treated
      empirically for cystitis or urinary tract infection from January 2001 to June
      2002 (n = 7738 patient-physician encounters). The proportion of cases treated
      according to the guidelines, with regard to duration, was calculated for each
      drug used. RESULTS: Rate of adherence was 3.36% for cases of TMP-SMX treatment
      (95%CI: 2.56%, 4.15%), 22.23% for nitrofurantoin (95%CI: 19.81%, 24.65%) and
      4.08% for ofloxacin (95%CI: 2.88%, 5.28%). The crude rate of adherence for all
      cases of treatment with these drugs was 8.67% (95%CI: 7.82%, 9.52%). CONCLUSIONS:
      The high rate of nonadherence observed (91.33%) indicate a need for a remedial
      education program for physicians to improve empiric treatment of urinary tract
      infection in women. Since this issue is of global importance, we believe our
      evaluation can serve as model for other settings and countries.

PMID- 15255091
TI  - A retrospective survey on the safety of Replenate, a high-purity factor VIII
      concentrate.
AB  - PURPOSE: To assess the safety of a highly purified, plasma-derived factor VIII
      concentrate (Replenate) in routine clinical use. METHODS: Following guidelines
      entitled safety assessment of marketed medicines (SAMM), safety data were
      collected in the UK on 194 patients who received an estimated 47.6 million IU of
      Replenate. This population included 47 patients undergoing 53 surgical operations
      or dental extractions. RESULTS: The study detected four cases of new factor VIII
      inhibitor development and twelve other adverse events, five that were unrelated
      to the product, five whose causality was unknown, one that was possibly product
      related and one case due to possible lack of efficacy. Only one of these cases
      had been notified to the manufacturer through conventional spontaneous reporting
      procedures. Three patients were switched from Replenate as a result of an adverse
      event (one case of infusion site irritation and two cases of a rise in titre of
      an existing inhibitor), but no unexpected adverse reactions were noted and there
      were no reports of virus transmission. The median factor VIII recovery value was
      2.17 IU/dl per IU/kg, but recovery was shown to be dependent on several
      variables, namely inhibitor status, treatment centre and the patient's body
      weight. The median factor VIII recovery in inhibitor-free patients was 2.28 IU/dl
      per IU/kg (range: 1.20-6.62). CONCLUSIONS: The study confirms that Replenate is
      well tolerated by the majority of patients in routine clinical practice.

PMID- 15255092
TI  - Risk factors...but only after excluding high-risk subjects.

PMID- 15255093
TI  - Looking to the 21st century: have we learned from our mistakes, or are we doomed
      to compound them?

PMID- 15255094
TI  - Do sexual ornaments demonstrate heightened condition-dependent expression as
      predicted by the handicap hypothesis?
AB  - The handicap hypothesis of sexual selection predicts that sexual ornaments have
      evolved heightened condition-dependent expression. The prediction has only
      recently been subject to experimental investigation. Many of the experiments are
      of limited value as they: (i) fail to compare condition dependence in sexual
      ornaments with suitable non-sexual trait controls; (ii) do not adequately account
      for body size variation; and (iii) typically consider no stress and extreme
      stress manipulations rather than a range of stresses similar to those experienced
      in nature. There is also a dearth of experimental studies investigating the
      genetic basis of condition dependence. Despite the common claim that sexual
      ornaments are condition-dependent, the unexpected conclusion from our literature
      review is that there is little support from well-designed experiments.

PMID- 15255095
TI  - Interference competition and parasite virulence.
AB  - Within-host competition between parasites, a consequence of infection by multiple
      strains, is predicted to favour rapid host exploitation and greater damage to
      hosts (virulence). However, the inclusion of biological variables can drastically
      change this relationship. For example, if competing parasite strains produce
      toxins that kill each other (interference competition), their growth rates and
      virulence may be reduced relative to single-strain infections. Bacteriocins are
      antimicrobial toxins produced by bacteria that target closely related strains and
      species, and to which the producing strain is immune. We investigated competition
      between bacteriocin-producing, insect-killing bacteria (Photorhabdus and
      Xenorhabdus) and how this competition affected virulence in caterpillars. Where
      one strain could kill the other, and not vice versa, the non-killing strain was
      competitively excluded, and insect mortality was the same as that of the killing
      strain alone. However, when caterpillars were multiply infected by strains that
      could kill each other, we did not observe competitive exclusion and their
      virulence was less than single-strain infections. The ubiquity and diversity of
      bacteriocins among pathogenic bacteria suggest mixed infections will be, on
      average, less virulent than single infections.

PMID- 15255096
TI  - Recurrent cerebellar architecture solves the motor-error problem.
AB  - Current views of cerebellar function have been heavily influenced by the models
      of Marr and Albus, who suggested that the climbing fibre input to the cerebellum
      acts as a teaching signal for motor learning. It is commonly assumed that this
      teaching signal must be motor error (the difference between actual and correct
      motor command), but this approach requires complex neural structures to estimate
      unobservable motor error from its observed sensory consequences. We have proposed
      elsewhere a recurrent decorrelation control architecture in which Marr-Albus
      models learn without requiring motor error. Here, we prove convergence for this
      architecture and demonstrate important advantages for the modular control of
      systems with multiple degrees of freedom. These results are illustrated by
      modelling adaptive plant compensation for the three-dimensional vestibular ocular
      reflex. This provides a functional role for recurrent cerebellar connectivity,
      which may be a generic anatomical feature of projections between regions of
      cerebral and cerebellar cortex.

PMID- 15255097
TI  - Extinction and biogeography in the Caribbean: new evidence from a fossil riodinid
      butterfly in Dominican amber.
AB  - We describe a new species of extinct riodinid butterfly, Voltinia dramba, from
      Oligo-Miocene Dominican amber (15-25 Myr ago). This appears to be the first
      butterfly to be taxonomically described from amber, and the first adult riodinid
      fossil. The series of five specimens represents probably the best-preserved
      fossil record for any lepidopteran. The phenomenon of extant Voltinia females
      ovipositing on arboreal epiphytes probably explains the discovery of multiple
      female V. dramba specimens in amber. Voltinia dramba appears to be one of many
      extinct butterfly species on Hispaniola. The northwestern Mexican distribution of
      the explicitly hypothesized sister species, the extant V. danforthi, supports the
      hypothesis that V. dramba reached Hispaniola by the 'proto-Greater Antillean
      arc', dating the divergence of V. dramba and V. danforthi to 40-50 Myr ago. This
      date is contemporaneous with the oldest known butterfly fossils, and implies a
      more ancient date of origin for many of the higher-level butterfly taxa than is
      often conceded.

PMID- 15255098
TI  - The effects of nectar addition on pollen removal and geitonogamy in the non
      rewarding orchid Anacamptis morio.
AB  - It has been suggested that the absence of floral rewards in many orchid species
      causes pollinators to probe fewer flowers on a plant, and thus reduces
      geitonogamy, i.e. self-pollination between flowers, which may result in
      inbreeding depression and reduced pollen export. We examined the effects of
      nectar addition on pollinator visitation and pollen transfer by tracking the fate
      of colour-labelled pollen in Anacamptis morio, a non-rewarding orchid species
      pollinated primarily by queen bumble-bees. Addition of nectar to spurs of A.
      morio significantly increased the number of flowers probed by bumble-bees, the
      time spent on an inflorescence, pollinarium removal and the proportion of removed
      pollen involved in self-pollination through geitonogamy, but did not affect
      pollen carryover (the fraction of a pollinarium carried over from one flower to
      the next). Only visits that exceeded 18 s resulted in geitonogamy, as this is the
      time taken for removed pollinaria to bend into a position to strike the stigma. A
      mutation for nectar production in A. morio would result in an initial 3.8-fold
      increase in pollinarium removal per visit, but also increase geitonogamous self
      pollination from less than 10% of pollen depositions to ca. 40%. Greater
      efficiency of pollen export will favour deceptive plants when pollinators are
      relatively common and most pollinaria are removed from flowers or when inbreeding
      depression is severe. These findings provide empirical support both for Darwin's
      contention that pollinarium bending is an anti-selfing mechanism in orchids and
      for the idea that floral deception serves to maximize the efficiency of pollen
      export.

PMID- 15255099
TI  - Optimal reproductive-skew models fail to predict aggression in wasps.
AB  - Optimal-skew models (OSMs) predict that cooperative breeding occurs as a result
      of dominants conceding reproductive benefits to subordinates, and that division
      of reproduction within groups reflects each cooperator's willingness and ability
      to contest aggressively for dominance. Polistine paper wasps are a leading model
      system for testing OSMs, and data on reproduction and aggression appear to
      support OSMs. These studies, however, measure aggression as a single rate rather
      than by the activity patterns of individuals. This leads to a potential error: if
      individuals are more likely to receive aggression when active than when inactive,
      differences in aggression across samples can reflect changes in activity rather
      than hostility. This study replicates a field manipulation cited as strongly
      supporting OSMs. We show that fundamentally different conclusions arise when
      controlling for individual activity states. Our analyses strongly suggest that
      behaviours classified as 'aggression' in paper wasps are unlikely to function in
      establishing, maintaining or responding to changes in reproductive skew. This
      illustrates that OSM tests using aggression or other non-reproductive behaviour
      as a metric for reproductive partitioning must demonstrate those links rather
      than assume them.

PMID- 15255100
TI  - A longitudinal analysis of reproductive skew in male rhesus macaques.
AB  - One of the basic tenets of sexual selection is that male reproductive success
      should be large in polygynous species. Here, we analysed 6 years of molecular
      genetic data from a semi-free-ranging population of rhesus macaques (Macaca
      mulatta), using Nonac's B index, to assess the level of male reproductive skew in
      the study troop. On average, the top sire in each year produced 24% of the
      infants, while 71% of troop males sired no offspring at all. Consequently, 74% of
      infants had at least one paternal half-sibling in their own birth cohort.
      Reproductive success was greatest for high-ranking males, males who spent the
      whole mating season in the troop and males of 9-11 years of age. Heterozygosity
      for major histocompatibility complex (MHC) class II gene DQB1 was the strongest
      single predictor of male reproductive success. A negative relationship suggestive
      of female mate choice was noted between the B index and the proportion of
      extragroup paternities. Reproductive skew was not associated with relatedness
      among potential sires or with female cycle synchrony. We conclude that
      reproductive skew in male rhesus macaques is best accounted for by the 'limited
      control' model, with multiple factors interacting to regulate individual
      reproductive output.

PMID- 15255101
TI  - Experimental evidence of a link between breeding conditions and the decision to
      breed or to help in a colonial cooperative bird.
AB  - In many species mature individuals delay independent reproduction and may help
      others to reproduce. This behaviour is often explained through ecological
      constraints, although recently attention has also been paid to the variation in
      habitat quality. If the quality of vacant habitat influences the fitness trade
      off between delaying reproduction and breeding independently, individuals should
      delay reproduction when conditions for breeding are poor. Yet, no study has
      experimentally manipulated habitat quality or the conditions experienced during
      the breeding period to test this assertion conclusively. We report results from
      an experiment conducted on a colonial cooperative bird with no territory
      constraints on reproduction. We artificially improved breeding conditions in
      several colonies of sociable weavers, Philetairus socius, through the provision
      of an easily obtainable and unlimited supply of food. We provide experimental
      evidence showing that under enhanced conditions some individuals reduce their age
      at first reproduction, a greater proportion of colony members engage in
      independent breeding and proportionally fewer birds act as helpers. Hence, these
      results also provide evidence for a direct influence of reproductive costs on
      life-history decisions such as age at first reproduction and breeding and helping
      behaviours.

PMID- 15255102
TI  - Nestling immunocompetence and testosterone covary with brood size in a songbird.
AB  - The social and ecological conditions that individuals experience during early
      development have marked effects on their developmental trajectory. In songbirds,
      brood size is a key environmental factor affecting development, and experimental
      increases in brood size have been shown to have negative effects on growth,
      condition and fitness. Possible causes of decreased growth in chicks from
      enlarged broods are nutritional stress, crowding and increased social
      competition, i.e. environmental factors known to affect adult steroid levels
      (especially of testosterone and corticosteroids) in mammals and birds. Little,
      however, is known about environmental effects on steroid synthesis in nestlings.
      We addressed this question by following the development of zebra finch
      (Taeniopygia guttata) chicks that were cross-fostered and raised in different
      brood sizes. In line with previous findings, nestling growth and cell-mediated
      immunocompetence were negatively affected by brood size. Moreover, nestling
      testosterone levels covaried with treatment: plasma testosterone increased with
      experimental brood size. This result provides experimental evidence that levels
      of circulating testosterone in nestlings can be influenced by their physiological
      response to environmental conditions.

PMID- 15255103
TI  - The mode of pheromone evolution: evidence from bark beetles.
AB  - Sex and aggregation pheromones consist of species-specific blends of chemicals.
      The way in which different species' blends have evolved has been the subject of
      some debate. Theoretical predictions suggest that differences between species
      have arisen not through the accruing of small changes, but through major shifts
      in chemical composition. Using data on the aggregation pheromones of 34 species
      of bark beetle from two genera, Dendroctonus and Ips, we investigated how the
      distributions of the chemical components of their pheromone blends mirror their
      phylogenetic relationships. We tested whether there were consistent patterns that
      could be used to help elucidate the mode of pheromone evolution. Although there
      were obvious differences in pheromone blends between the two genera, the
      differences between species within each genus followed a less clear phylogenetic
      pattern. In both genera, closely related species are just as different as more
      distantly related species. Within Dendroctonus, particularly, most chemical
      components were distributed randomly across the phylogeny. Indeed, for some
      chemicals, closely related species may actually be more different than would be
      expected from a random distribution of chemical components. This argues strongly
      against the idea of minor shifts in pheromone evolution. Instead, we suggest
      that, within certain phylogenetic constraints, pheromone evolution in bark
      beetles is characterized by large saltational shifts, resulting in sibling
      species being substantially phenotypically (i.e. pheromonally) different from one
      another, thus agreeing with theoretical predictions.

PMID- 15255104
TI  - Fitness consequences of avian personalities in a fluctuating environment.
AB  - Individual animals differ in the way they cope with challenges in their
      environment, comparable with variation in human personalities. The proximate
      basis of variation in personality traits has received considerable attention, and
      one general finding is that personality traits have a substantial genetic basis.
      This poses the question of how variation in personality is maintained in natural
      populations. We show that selection on a personality trait with high heritability
      fluctuates across years within a natural bird population. Annual adult survival
      was related to this personality trait (behaviour in novel environments) but the
      effects were always opposite for males and females, and reversed between years.
      The number of offspring surviving to breeding was also related to their parents'
      personalities, and again selection changed between years. The observed annual
      changes in selection pressures coincided with changes in environmental conditions
      (masting of beeches) that affect the competitive regimes of the birds. We expect
      that the observed fluctuations in environmental factors lead to fluctuations in
      competition for space and food, and these, in association with variations in
      population density, lead to a variation in selection pressure, which maintains
      genetic variation in personalities.

PMID- 15255105
TI  - The evolution of brain lateralization: a game-theoretical analysis of population
      structure.
AB  - In recent years, it has become apparent that behavioural and brain lateralization
      at the population level is the rule rather than the exception among vertebrates.
      The study of these phenomena has so far been the province of neurology and
      neuropsychology. Here, we show how such research can be integrated with
      evolutionary biology to understand lateralization more fully. In particular, we
      address the fact that, within a species, left- and right-type individuals often
      occur in proportions different from one-half (e.g. hand use in humans). The
      traditional explanations offered for lateralization of brain function (that it
      may avoid unnecessary duplication of neural circuitry and reduce interference
      between functions) cannot account for this fact, because increased individual
      efficiency is unrelated to the alignment of lateralization at the population
      level. A further puzzle is that such an alignment may even be disadvantageous, as
      it makes individual behaviour more predictable to other organisms. Here, we show
      that alignment of the direction of behavioural asymmetries in a population can
      arise as an evolutionarily stable strategy when individual asymmetrical organisms
      must coordinate their behaviour with that of other asymmetrical organisms. Brain
      and behavioural lateralization, as we know it in humans and other vertebrates,
      may have evolved under basically 'social' selection pressures.

PMID- 15255106
TI  - Disease dynamics in cyclic populations of field voles (Microtus agrestis): cowpox
      virus and vole tuberculosis (Mycobacterium microti).
AB  - The possible role of pathogens in rodent population cycles has been largely
      neglected since Elton's 'epidemic hypothesis' of 1931. To revisit this question,
      12 adjacent, cyclic but out-of-phase populations of field voles (Microtus
      agrestis) in North East England were studied and the initial results are
      presented here. The prevalences of antibodies to cowpox virus and of clinical
      signs of Mycobacterium microti infection (vole tuberculosis) showed delayed (not
      direct) density dependence (with a lag of three to six months). This did not
      result from changes in population structure, even though there were such changes
      associated with the different phases of the cycle. The prevalences rose as vole
      numbers rose, and peaked as numbers declined. The apparent lag in the numerical
      response of infection prevalence to changes in host abundance is consistent with
      the hypothesis that diseases, singly or in combination, play a hitherto
      underestimated role in the dynamics of cyclic populations.

PMID- 15255108
TI  - Rapid population decline in red knots: fitness consequences of decreased
      refuelling rates and late arrival in Delaware Bay.
AB  - Most populations of migrant shorebirds around the world are in serious decline,
      suggesting that vital condition-dependent rates such as fecundity and annual
      survival are being affected globally. A striking example is the red knot
      (Calidris canutus rufa) population wintering in Tierra del Fuego, which
      undertakes marathon 30,000 km hemispheric migrations annually. In spring, migrant
      birds forage voraciously on horseshoe crab eggs in Delaware Bay in the eastern
      USA before departing to breed in Arctic polar deserts. From 1997 to 2002 an
      increasing proportion of knots failed to reach threshold departure masses of 180
      200 g, possibly because of later arrival in the Bay and food shortage from
      concurrent over-harvesting of crabs. Reduced nutrient storage, especially in late
      arriving birds, possibly combined with reduced sizes of intestine and liver
      during refuelling, had severe fitness consequences for adult survival and
      recruitment of young in 2000-2002. From 1997 to 2002 known survivors in Delaware
      Bay were heavier at initial capture than birds never seen again, annual survival
      of adults decreased by 37% between May 2000 and May 2001, and the number of
      second-year birds in wintering flocks declined by 47%. Population size in Tierra
      del Fuego declined alarmingly from 51,000 to 27,000 in 2000-2002, seriously
      threatening the viability of this subspecies. Demographic modelling predicts
      imminent endangerment and an increased risk of extinction of the subspecies
      without urgent risk-averse management.

PMID- 15255107
TI  - Allele excess at neutrally evolving microsatellites and the implications for
      tests of neutrality.
AB  - Skews in the observed allele-frequency spectrum are frequently viewed as an
      indication of non-neutral evolution. Recent surveys of microsatellite variability
      have used an excess of alleles as a statistical approach to infer positive
      selection. Using neutral coalescent simulations we demonstrate that the mean
      numbers of alleles expected under the stepwise-mutation model and infinite-allele
      model deviate from the observed numbers of alleles. The magnitude of this
      difference is dependent on the sample size, mutation rates (theta-values) and
      observed gene diversities. Moreover, we show that the number of observed alleles
      differs among loci with the same observed gene diversity but different mutation
      rates (theta-values). We propose that a reliable test statistic based on allele
      excess must determine the confidence interval by computer simulations conditional
      on the observed gene diversity and theta-values. As the latter are notoriously
      difficult to obtain for experimental data, we suggest that other statistics, such
      as lnRV, may be better suited to the identification of microsatellite loci
      subject to selection.

PMID- 15255110
TI  - Genetic analysis of an Indian family with members affected with juvenile-onset
      primary open-angle glaucoma.
AB  - PURPOSE: Glaucoma is the second leading cause of blindness. In India,
      approximately 1.5 million people are blind due to glaucoma. Mutations in the MYOC
      gene located at the GLC1A locus on chromosome 1q21-q31 have been found in
      patients with juvenile-onset primary open-angle glaucoma (J-POAG). The purpose of
      the present study was to identify the genetic cause of glaucoma in a four
      generation Indian family affected with J-POAG. METHODS: Peripheral blood samples
      were obtained from individuals for genomic DNA isolation. To determine if this
      family was linked to the GLC1A locus, haplotyping analysis was carried out using
      microsatellite markers from the GLC1A candidate region. Exon-specific primers
      from exon 3 of the MYOC gene were used to amplify DNA samples from individuals.
      Mutation analysis was carried out using PCR-SSCP and DNA sequence analyses.
      RESULTS: Pedigree analysis suggested that glaucoma in this family segregated as
      an autosomal dominant trait. Of six patients, five had J-POAG and one had adult
      onset POAG (A-POAG). Haplotype analysis suggested linkage of this family to the
      GLC1A locus. Mutation and sequence analyses showed a novel missense mutation,
      c.821C > G (p.P274R), in the C-terminal olfactomedin domain coded by exon 3 of
      the MYOC gene. One patient was found to be homozygous for this mutation with a
      severe phenotype. CONCLUSIONS: This study reports a novel missense mutation in a
      four-generation Indian family with all but one member affected with J-POAG. The
      total number of mutations described so far in the MYOC gene, including the one
      reported here, is 59 with a clustering of 52 mutations in exon 3.

PMID- 15255109
TI  - Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in
      Ecuador.
AB  - PURPOSE: To determine the role of cytochrome P450IBI (CYP1B1) mutations in
      causing primary congenital glaucoma (PCG) in a cohort of Native Americans from
      Quito, Ecuador. MATERIALS AND METHODS: Seventeen patients with PCG from 15 Native
      American families were recruited from the Ophthalmology Clinic at Hospital
      Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected
      study subjects. Purified DNA was prepared from peripheral blood samples and
      CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot
      was performed only on those affected patients who showed no mutations in the
      CYP1B1 coding exons. RESULTS: The molecular basis of PCG in two families was
      determined: two novel mutations (a deletion and a point mutation) and one novel
      polymorphism in CYP1B1 were identified in addition to a previously described
      single amino acid substitution. Southern blot analyses on whole genomic DNA from
      affected individuals in whom no mutations were identified by the direct
      PCR/sequencing approach did not detect any large rearrangements or mutations
      outside the coding region. CONCLUSION: These findings suggest that mutations in
      CYPIBI are not a major cause of PCG in this population and that at least one
      additional locus for this condition is responsible for most cases. Further, the
      PCG phenotype did not correlate readily with the molecular basis of the disorder,
      suggesting that careful clinical analysis of the phenotype cannot predict the
      molecular basis of the disease with accuracy.

PMID- 15255111
TI  - Lack of activity of oral etoposide for relapsed intraocular retinoblastoma.
AB  - BACKGROUND: Intravenous etoposide is widely used in multiagent chemotherapy
      regimens for intraocular retinoblastoma despite the lack of phase II data
      documenting its efficacy. Because oral etoposide has been found to be highly
      effective in patients with relapsed medulloblastoma and neuroblastoma who had
      previously received intravenous etoposide, we investigated its use for
      intraocular retinoblastoma. PROCEDURE: A pilot trial of oral etoposide (50 mg/m2/
      day for 21 days) in five children (6 eyes) with relapsed refractory intraocular
      retinoblastoma was performed. All had previously received chemotherapy, including
      intravenous etoposide in four patients, and all had received radiation therapy.
      Three patients (3 eyes) had vitreous seeds. Response was evaluated after one
      cycle. RESULTS: No serious acute toxicity was encountered, and no responses were
      noted. Four patients (5 eyes) had progressive disease. Stable disease was noted
      in one eye without vitreous disease. One patient developed secondary acute
      myeloid leukemia 30 months after exposure to oral etoposide. CONCLUSIONS: Oral
      etoposide was not an effective agent in this population. The role of etoposide in
      the treatment of higher risk intraocular retinoblastoma deserves further study.

PMID- 15255112
TI  - Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital
      retinoblastoma in the eye: preliminary experience.
AB  - BACKGROUND/AIMS: To report our first experience with FDG-PET in the detection of
      vital retinoblastoma. METHODS: Four newly diagnosed retinoblastoma patients, two
      treated retinoblastoma patients, and four control patients were enrolled in this
      pilot study. F18-FDG uptake was assessed in the light of clinical and
      histopathological features. RESULTS: PET discriminated between new patients and
      controls, although tumor uptake varied widely. PET added no useful information
      with regard to possible vital tissue in tumor scars in the eye of the two treated
      retinoblastoma patients. Moreover, PET findings did not correlate with clinical
      or histopathological features. CONCLUSION: Based on this small pilot study, F18
      PET shows little promise in the detection of retinoblastoma. More research on
      other radiofarmacons is recommended.

PMID- 15255113
TI  - Activity of topotecan in retinoblastoma.
AB  - PURPOSE: To report our experience with topotecan in children with
      relapsed/refractory metastatic and intraocular retinoblastoma. PATIENTS AND
      METHODS: Topotecan was administered intravenously as a 30-min infusion at a dose
      of 2 mg/m2/d for five consecutive days and repeated after three weeks. If obvious
      progression was detected by physical examination in patients with overt
      extraocular disease or if progressive disease was noted after fundoscopic
      examination in patients with intraocular disease, a second cycle was not
      administered. Response was evaluated at Week 6. RESULTS: Nine patients (6
      extraocular, 3 intraocular) were treated from November 1998 to March 2002. A
      total of 16 cycles were administered. In patients with extraocular disease, there
      were three partial responses, two cases of stable disease, and one case of
      progressive disease. Two patients with relapsed/resistant intraocular disease had
      partial response. allowing local therapy to be performed, and the third patient
      had progressive disease. The drug was well-tolerated. No patient developed fever
      or documented infections. No other serious toxicity was found. CONCLUSION:
      Topotecan is active in extraocular and relapsed/resistant intraocular
      retinoblastoma. The role of this drug in the treatment of retinoblastoma should
      be explored in further studies.

PMID- 15255114
TI  - A second primary tumor in a patient with retinoma.
AB  - AIM: To evaluate the frequency of the co-occurrence of a retinoma and another
      primary tumor. METHOD: Presentation of a case report and review of the
      literature. RESULTS: A cutaneous melanoma was observed in a 52-year-old man, who
      was known to have two retinomas in the right eye. Five other cases were found in
      a review of the literature, suggesting the possibility of an increased risk of
      developing a second primary tumor in patients with retinoma. The occurrence of
      cutaneous melanoma as a second primary tumor after retinoma and/or retinoblastoma
      is discussed. CONCLUSION: There might be an increased risk for patients with
      retinoma to develop another primary tumor, necessitating regular follow-up of
      these patients.

PMID- 15255115
TI  - Neurofibromatosis type 1 associated with central nervous system lymphoma.
AB  - PURPOSE: To report the occurrence of central nervous system (CNS) lymphoma in a
      patients with neurofibromatosis type 1 (NF1). DESIGN: Interventional case report.
      METHODS: A 47-year-old male with a parieto-occipital lobe lesion was referred for
      ocular evaluation. Skin, brain, and vitreous biopsies were performed. RESULTS:
      The discovery of Lisch nodules of the iris prompted a physical examination that
      revealed cutaneous stigmata of NF1. Biopsy of the CNS lesion revealed diffuse
      large B-cell lymphoma. Biopsy of papules on the back and abdomen were compatible
      with neurofibroma. No malignant cells were found in the vitreous specimen. A
      clinical diagnosis of NF1 was made. CONCLUSION: This is the first report of CNS
      lymphoma in a patient with NF1. Additional reports may shed more light on the
      possible association between the two conditions.

PMID- 15255116
TI  - Ocular manifestations of mosaic trisomy 22: a case report and review of the
      literature.
AB  - Mosaic trisomy 22 is rare, but can be compatible with prolonged life. Patients
      with mosaic trisomy 22 usually present with intrauterine growth retardation,
      mental retardation, failure to thrive, and craniofacial asymmetry. We report the
      case of a five-year-old boy who had a birth weight of 3.8 kg and normal
      developmental milestones. He presented with unilateral ocular manifestations of
      ptosis, double elevator palsy, high myopia, and choroidal coloboma involving the
      macula. Cytogenetic evaluation showed a low level of trisomy 22 in peripheral
      blood lymphocytes (1 in 100) and in cultured fibroblasts from a conjunctival
      biopsy of the affected eye (1 in 60). Our case demonstrates the value of
      chromosomal analysis of the tissues involved rather than just karyotyping of the
      blood lymphocytes to detect mosaicism in patients with localised and unilateral
      congenital malformations.

PMID- 15255117
TI  - A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome.
AB  - PURPOSE: To determine the underlying genetic cause of Axenfeld-Rieger syndrome
      (ARS) in a three-generation family. INTRODUCTION: ARS is a multisystem, autosomal
      dominant disorder characterized by specific ocular and non-ocular anomalies
      sometimes caused by mutations in the transcription factor gene, PITX2. METHODS:
      The three coding exons of the PITX2 gene, i.e., exons 2, 3, and 4, in affected
      and unaffected subjects were amplified by polymerase chain reaction (PCR) and
      sequenced. The PCR products of exon 4 were subcloned and sequenced to confirm the
      nature of the mutation. RESULTS: A deletion of thymine (T) 1261 was identified,
      creating a frameshift mutation in codon 227. This change is predicted to create
      11 novel amino acids downstream, followed by premature truncation of the protein.
      CONCLUSIONS: This mutation highlights the functional importance of a conserved 14
      amino acid sequence at the C-terminus of the protein thought to be important in
      repressing DNA binding and in protein-protein interactions.

PMID- 15255119
TI  - Thrombotic thrombocytopenia purpura: an update.

PMID- 15255118
TI  - Redefining the syndromes of thrombotic microangiopathy.

PMID- 15255120
TI  - State of the art of low-density lipoprotein apheresis in the year 2003.
AB  - Low-density lipoprotein (LDL) apheresis is a last-resort treatment for
      hypercholesterolemic patients resistant to conservative lipid-lowering therapy.
      In the extracorporeal circuit, LDL, Lp(a) and coagulation factors are selectively
      eliminated, while the beneficial proteins like high-density lipoprotein, albumin
      and immunoglobulins are returned to the patient. Clinical effects of LDL
      apheresis comprise improvement of symptoms like angina and exercise tolerance,
      reduction of clinical coronary events like unstable angina, need for angioplasty
      or bypass operation, myocardial infarction and ultimately coronary mortality. The
      reduction of atherogenic lipoproteins and of coagulation factors by LDL apheresis
      (LA) positively influences hemorheology, endothelial function and coronary
      reserve. In the controlled LAARS, LA significantly improved the
      electrocardiographic signs of myocardial ischemia in the treadmill test. In
      angiographically controlled trials such as LARS and L-CAPS, a reduction of
      progression of coronary lesions was observed; in favorable cases, regression of
      the stenoses could be documented. In addition, in the LDL apheresis coronary
      morphology trial, LA decreased the coronary plaque area. The Hokuriku trial
      documented a 72% decrease of coronary events (MACE) in the LA group vs. controls
      treated only by statins. In longitudinal studies, the incidence of MACE after
      regular LA decreased compared with the preapheresis period in the same patients.
      Apart from coronary heart disease, recent studies indicate a positive effect of
      LA also on carotid artery stenoses and peripheral vascular disease. Prospective
      randomized studies showed the beneficial effects of cascade filtration on age
      related macular degeneration and of heparin-induced LDL precipitation apheresis
      on acute inner ear deafness.

PMID- 15255121
TI  - Thrombotic thrombocytopenic purpura: yesterday, today, tomorrow.
AB  - Although much has been learned about the pathophysiologic process of thrombotic
      thrombocytopenic purpura (TTP), both diagnostically and therapeutically, since
      its initial description by Moschcowitz in 1924, its etiology and treatments
      remain, in many instances, problematic. Thrombotic thrombocytopenic purpura
      remains a rare entity whose etiology is usually unknown, but several drugs and
      infections have now been implicated in its development (i.e. Cyclosporine A,
      Mitomycin-C, Ticlopidine, Simvastatin, Lipitor, Plavix, FK 506, Rapamune
      (sirolimus), HIV). Although its treatment by plasma exchange has gained worldwide
      acceptance since the late 1970s, the optimal exchange media is not known, nor the
      volume and duration of exchange therapy, nor appropriate salvage therapy(ies).
      Without the benefit of randomized controlled trials, its treatment, to a large
      extent, remains not evidence-based but 'eminence-based', making the same mistakes
      with increasing confidence over an impressive number of years.

PMID- 15255122
TI  - Nine years of cascade filtration for thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) continues to attract physicians'
      attention because of its unpredictable course and underlying pathogenetic
      mechanisms. It is also attractive because of its optimal response to therapeutic
      plasma exchange (PE) even in the most severe cases. The usual approach to its
      treatment is conventional PE with plasma substitution and only recently fresh
      frozen plasma (FFP) has been substituted by cryodepleted or virally inactivated
      plasma with clinical results that are, if not better, at least comparable with
      the ones attained when FFP is employed. Nonetheless, no consensus exists
      regarding the optimal PE fluid and this is not of marginal interest as even after
      PE treatment mortality is still from 15 to 20%. On the contrary, some consensus
      exists on the pathogenetic relevance of the exceedingly large Von Willebrand
      (vWF) multimers whose presence parallels the clinical course and appears to be
      determined by the abnormalities in the production or function and survival of vWF
      cleaving proteases which is auto-antibody mediated. In both cases plasmapheresis
      without plasma infusion is relatively ineffective, perhaps because it does not
      increase protease activity. Paradoxically, cascade filtration (CF) can produce
      the same favorable results without replacing any protease activity. As with CF,
      the replacement is the autologous plasma with approximately 20% levels of vWF,
      fibrinogen, fibronectin, IgM and circulating immune complexes and 75% of albumin,
      IgGs, AT III and proteins whose molecular weight exceeds 250-300000 Da. Our
      experience with CF for TTP began in 1994. Since then, 16 patients have undergone
      CF combined with decreasing amounts of FFP supplementation and since 1998 without
      any allogeneic FFP supplementation in 9 cases. Twenty-four patients (96%) treated
      with no or minimal amounts of FFP survived but four (16%) experienced from one to
      four recurrences associated with cutaneous, paradental, cholecystic and vaginal
      infections. Only one patient died (5%) after the second CF procedure. There were
      no untoward effects related to the procedure itself and up to 18 procedures in
      one patient were carried out over 16 months, 10 with the patient in her sixth
      month of pregnancy and four in the post partum period in preparation for a
      splenectomy. Remission was achieved after an average number of treatments (10.7
      +/- 6.8); a result that compares favorably with those of our historical control
      group of 47 cases (14 +/- 13). The patient's exposure to allogenic plasma which
      was 10.8 +/- 4.6 plasma U/session was reduced to 0 in 10 patients, to 1.4 +/- 1.2
      and 4.4 +/- 2.3 plasma U/session, respectively, for seven and nine patients
      receiving PE + CF and CF with same plasma supplementation as described in our
      previous article. Based on our experience, we believe CF is presently the optimal
      treatment for patients with classic, sporadic TTP.

PMID- 15255123
TI  - Multicomponent donor apheresis in the Americas.
AB  - Multicomponent donor apheresis utilizes apheresis technology to collect
      combinations of red blood cells, platelets and plasma units. The United States
      has embraced this technology to the greatest extent of the countries in the
      Americas. As whole blood and apheresis collection have increased, so have the
      donor deferrals based on potential exposure to infectious agents. However,
      hemoglobin/hematocrit deferrals still remain the largest upfront deferral for
      volunteer donors. As the technology is refined in future years, multicomponent
      donor apheresis may become the predominant method of collecting blood products
      from donors.

PMID- 15255124
TI  - Current status of therapeutic plasma exchange in Korea.
AB  - A nationwide survey on the status of plasma exchange in Korea was performed
      during the 2 year period 2001-02. Data from 496 patients were collected from 15
      major hospitals. The most common indication was myasthenia gravis (15.3%),
      followed by thrombotic thrombocytopenic purpura (14.5%) and hemolytic uremic
      syndrome (9.7%). Clinical improvement was noted in 70.1% of the 415 cases. Plasma
      exchange by centrifugation alone accounted for 92.4%. Postcentrifugal filtration
      was carried out in 5.6% and double filtration in 2.0% of treatments. The most
      common instruments for the centrifugation were Cobe Spectra (71.3%) and Fenwal
      CS3000 (15.8%). Filtration was performed by either Kuraray KM8300 or Kuraray
      KM8800. The overall frequency of complications was 11.1% (293/2647 cases), of
      which symptomatic hypocalcemia was the most common (2.3%).

PMID- 15255125
TI  - Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a
      concise review.
AB  - An extensive variety of drugs have been associated with thrombotic
      thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Although a
      direct causal effect has usually not been proven, the cumulative evidence linking
      several drugs with TTP/HUS is strong. This paper reviews several categories of
      drugs including antineoplastics, immunotherapeutics and anti-platelet agents that
      have been reported to induce TTP/HUS. The pathogenesis of drug-induced TTP/HUS
      and the effectiveness of treatment regimens are also reviewed. A consensus on
      diagnostic criteria to accurately and consistently diagnose drug-induced TTP is
      needed.

PMID- 15255126
TI  - Evidence-based medicine for apheresis: an ongoing challenge.
AB  - Although much has been learned about the pathophysiologic process of thrombotic
      thrombocytopenic purpura (TTP) since Moschcowitz's initial description in 1924,
      its etiology and treatments remain problematic. We treated our first patient with
      TTP by plasma exchange in 1975 and have now treated over 160 patients. We report
      our experience exchanging patients using FFP, solvent detergent (SD) and cryopoor
      plasma as the exchange media. Most patients experience allergic reactions, some
      severe, during the course of treatment. However, use of SD plasma virtually
      eliminates all allergic reactions. Splenectomy was a much more common treatment
      prior to plasma exchange, but can still be a useful treatment option for some
      refractory patients. Recombinant ADAMTS-13 can hopefully provide not only more
      useful diagnostic assays but also could provide specific and more efficacious
      treatment of patients with both acquired and familial forms of TTP.

PMID- 15255127
TI  - Apheresis technologies and clinical applications: the 2002 international
      apheresis registry.
AB  - The developments in apheresis technologies and techniques and their clinical
      applications worldwide are technologically, sociologically, and economically
      motivated. In past apheresis surveys, the statistics have highlighted both the
      differences by geographic region in clinical practice and in the types of
      technologies utilized. While a national view of apheresis is very important, an
      international view may be more representative overall of this therapeutic
      modality than national results that are highly dependent on the local economics
      and the available technologies. These regional differences have provided a basis
      for scientific and clinical assessment of these apheresis technologies and their
      clinical outcomes and have impacted the marketing and business developments of
      new technologies worldwide. The results of the International Apheresis Registry
      for 2002, reporting on 33 centers on four continents, are presented. The survey
      collected data, predominantly via an internet website, on 811 patients for a
      total of 11 428 treatments. Information gathered included patient demographics,
      medical history, treatment diagnoses, treatment specifics (type, methodology,
      access type, anticoagulants, drugs, and equipment usage), side-effects, clinical
      response, and payment provider. As in the prior International Apheresis
      Registries for 1983 and 2000, the survey results highlight the regional
      differences in apheresis usage and treatment specifics, indicating that an
      international overview of apheresis may be more representative of the impact of
      this therapeutic modality.

PMID- 15255128
TI  - Effects of replacement fluids on plasma viscosity used for therapeutic plasma
      exchange.
AB  - Plasmapheresis is a widely used alternative treatment for several diseases.
      Recently, synthetic plasma expanders have been used to reduce the cost of
      therapeutic plasma exchange (TPE). Hydroxyethyl starch (HES) is a polysaccharide
      colloid. Isohes and Varihes are plasma volume expanders containing 6% HES in 0.9%
      NaCl solution. In this study, we aimed to compare the effects of several
      replacement fluids used for TPE on plasma viscosity profile. At the same time, we
      evaluated the correlation between plasma viscosity and fibrinogen level. Twenty
      nine patients were enrolled for this study. Patients were divided into four
      groups based on replacement fluids used: 3% HES + 4% albumin (group 1), FFP
      (group 2), 3% Varihes (450000/ 0.7)/Isohes(200000/0.5) (group 3), and 4% albumin
      (group 4). The choice of replacement fluids used was randomly assigned, as long
      as there were no contraindications for the patient. Seven samples were collected
      to determine plasma viscosity and fibrinogen level during TPE cycles. There was a
      positive exponential correlation between plasma viscosity and fibrinogen levels.
      At the second plasmapheresis procedure, plasma viscosity and fibrinogen levels
      decreased by 20% compared with first cycle. The effect of plasmapheresis
      solutions on hemorheology were roughly the same. Effects of replacement fluids on
      plasma viscosity were comparable.

PMID- 15255129
TI  - Rapid improvement of acute pulmonary edema with angiotensin converting enzyme
      inhibitor under hemodialysis in a patient with renovascular disease.
AB  - A 71-year-old man with bilateral renovascular disease was admitted to Hamamatsu
      University hospital because of appetite loss and acute shortness of breath due to
      acute pulmonary edema (APE) with accelerated hypertension and renal failure.
      Hypertension and APE were controlled by an angiotensin converting enzyme
      inhibitor (ACEI) and four sessions of hemodialysis with reduction of 1.8 kg
      bodyweight. Renal function was later stabilized and the patient required no ACEI
      or hemodialysis. A trial of right renal angioplasty 1 month after admission
      failed and renal function deteriorated (serum creatinine 7.1 mg/dL) with
      accelerated hypertension, gain of bodyweight and APE. Even after four sessions of
      hemodialysis with adequate reduction of bodyweight, APE was not controlled, but
      it rapidly improved after administration of an ACEI, without major bodyweight
      change. As no apparent cardiac dysfunction was evident, APE might have been
      caused by a direct action of angiotensin II on hyperpermeability in pulmonary
      capillaries. Blocking of angiotensin II should be considered in such patients
      even after introduction of hemodialysis.

PMID- 15255130
TI  - The series-parallel circuit in the treatment of fulminant hepatitis.
AB  - We developed a series-parallel treatment method for combined plasma exchange (PE)
      and continuous hemodiafiltration (CHDF) therapy in fulminant hepatitis. We then
      compared total serum bilirubin, citrate, and cytokine levels obtained by the new
      methods to those obtained with treatment by the single and reverse-parallel PE
      methods. Ten adult patients with fulminant hepatitis consented to participate.
      Plasma exchange was conducted 25 times by the single method (PE only), 16 times
      by the reverse-parallel method, and 37 times by the series-parallel method. The
      percentage of total bilirubin removed was highest with the single method followed
      in order by that with the series-parallel and reverse-parallel methods; the
      differences were significant. The percentage increase in citrate level was
      highest with the single method, followed in order by that with the series
      parallel and the reverse-parallel methods; these differences were also
      significant. There was no significant difference in serum interleukin (IL)-6
      levels after PE, by the single or the reverse-parallel methods. However, the IL-6
      level decreased significantly following PE by the series-parallel method. The
      serum IL-18 level decreased significantly following PE by each of the three
      methods. Thus, removal of excess bilirubin, citrate, and cytokines by the series
      parallel method, a simple maneuver with excellent removal rates, was considered
      effective.

PMID- 15255131
TI  - Osteal complications as first manifestation in a patient with primary Sjogren's
      Syndrome and with associated distal tubular acidosis (type 1) and chronic renal
      insufficiency.
AB  - Renal affection is among the complications associated with the Sjogren's
      Syndrome. Tubulo-interstitial nephritis constitutes the most frequent renal
      lesion and distal tubular acidosis (Type 1) is the most important clinical
      manifestation of this tubular dysfunction, although the occurrence of chronic
      renal insufficiency is not an uncommon finding in the presence of distal renal
      tubular acidosis. Osteomalacia is a clinical consequence of tubular acidosis
      caused by buffering of H+ in the bone. We present the case of a woman with osteal
      complication a year before being diagnosed with primary Sjogren's Syndrome and
      with distal tubular acidosis and renal insufficiency associated at diagnosis.

PMID- 15255132
TI  - The salvage of graft occlusion in a maintenace hemodialysis patient with tuberous
      sclerosis by percutaneous transluminal angioplasty using intravascular
      ultrasound: case report.
AB  - End-stage renal failure due to tuberous sclerosis is rare and there is no
      previous report of a patient with tuberous sclerosis undergoing long-term
      hemodialysis for over 18 years. The patency rate for a dialysis prosthetic graft
      is low, however, our patient's graft survived over 16 years. For thrombotic
      occlusion of a graft, we performed percutaneous thrombectomy and balloon
      angioplasty and salvaged graft occlusion. Moreover, this case is the first report
      in which the interventional procedure (mechanical thrombectomy and balloon
      angioplasty) could be observed by intravascular ultrasound in addition to
      angiography.

PMID- 15255133
TI  - Social isolation syndrome in rats.

PMID- 15255134
TI  - Phasic coordination between locomotor and respiratory rhythms in the mollusk
      lymnaea: transmitter-specific modifications.

PMID- 15255135
TI  - The role of CD 14-associated molecules in the immunomodulating activity of
      chorionic gonadotropin.

PMID- 15255136
TI  - Influence of severe hypoxia on rat emotional behavior: the modifying effect of
      preconditioning.

PMID- 15255137
TI  - Functional activity of human monocytes exposed to lipopolysaccharides of
      different structure.

PMID- 15255138
TI  - Functional states of synaptically controlled excitable membrane.

PMID- 15255139
TI  - Effects of exogenous heat shock protein (Hsp70) on glutaminergic synaptic
      transmission in rat olfactory cortex in vitro.

PMID- 15255140
TI  - Characteristics of craniogenesis in the axolotl (Ambystoma mexicanum:
      Ambystomatidae) and the role of thyroid hormones in its regulation.

PMID- 15255141
TI  - The characteristics of the helminthofauna of sea birds of the Svalbard
      archipelago.

PMID- 15255142
TI  - Ethylene-induced production of cadaverine is mediated by protein phosphorylation
      and dephosphorylation.

PMID- 15255143
TI  - An improved tolerance of PHYB-transgenic potato plants to the middle-wave
      ultraviolet irradiation.

PMID- 15255145
TI  - Global warming and variation in the chromosomal composition of Siberian molaria
      mosquito populations.

PMID- 15255144
TI  - Reversibility of the stress-induced development of CAM photosynthesis in plants.

PMID- 15255146
TI  - Signaling pathways of the phytohormonal stimulation of root pumping activity.

PMID- 15255147
TI  - The information value of fatty acid composition of triacylglycerols and polar
      lipids of seston in assaying the food spectrum of microzooplankton in the bugach
      reservoir.

PMID- 15255148
TI  - The use of light microscopy for three-dimensional reconstruction of early embryos
      of mammals.

PMID- 15255149
TI  - Some immunological and biochemical indices of the Black Sea bottlenose dolphin
      (Tursiops truncatus) during adaptation to the captivity conditions.

PMID- 15255150
TI  - Specificity of the hemoglobin fraction composition in the Sakhalin sturgeon
      Acipenser medirostris.

PMID- 15255151
TI  - Changes in catalase activity in potato tubers, induced by immunoregulators.

PMID- 15255152
TI  - Identification of the potential gene that controlling cotyledon development in
      Arabidopsis thaliana seedlings.

PMID- 15255153
TI  - New characteristics of Drosophila mutation Rad(2)201G1: epigenetic transmission
      of a repair defect via meiosis and association with the Rad51C gene.

PMID- 15255154
TI  - LAK cells kill Fas- cancer cells using the Tag7/Hsp70 protein complex secreted
      from the Golgi apparatus.

PMID- 15255155
TI  - HSP70 forms a stable cytotoxic complex with Tag7/PGRP-S.

PMID- 15255156
TI  - Changes of chromosomes and cell cycle (endoreduplication, somatic crossing-over,
      and robertsonian fusions) in hepatocytes of senescence accelerated SAMR1 mice.

PMID- 15255158
TI  - The impact of "ancient pathogen" studies on the practice of public health.
AB  - A new field of "ancient pathogens" is making an impact on our concepts of the
      evolution of infectious diseases, and it will eventually alter the practice of
      public health in their control. It has begun to answer important questions
      regarding past epidemics of influenza and tuberculosis by recovering the genetic
      sequences of the ancient causative agents. Vaccination strategics will have to
      study these microbial variants in order to develop tomorrow's vaccines. It may
      also be possible to examine the role of past and present reservoirs in the
      dynamics of emerging diseases. In unraveling the evolution of pathogens, insights
      into the mechanisms of drug and antibiotic resistance are possible. As "genome
      projects" of more and more pathogens are being completed. Targets for
      chemotherapy are being revealed which are totally different from the metabolic
      processes of the mammalian host. Signal molecules are being identified which
      alter the virulence of the microbe. Focussing on these mechanisms without
      attempting to kill the pathogen may in some cases drive it into a benign state.
      These and other aspects of the evolution of pathogens are discussed which may
      lead to innovative approaches to the control of infectious diseases.

PMID- 15255157
TI  - The hexapeptide immunofan inhibits the MRP-dependent multidrug resistance of
      tumor cells.

PMID- 15255159
TI  - Understanding college students' salient attitudes and beliefs about smoking:
      distinctions between smokers, nonsmokers, and ex-smokers.
AB  - This research examines the salient attitudes and beliefs that college students
      hold about cigarette smoking. An exploratory survey was employed that contained a
      combination of semantic differential items and open-ended questions. The data
      indicated that smoking status (i.e., whether a student is a nonsmoker, smoker, or
      ex-smoker) was related to attitudes about the attractiveness, riskiness, and
      intelligence of cigarette smoking. Additionally, salient beliefs about smoking
      include that nonsmokers report never smoking due to health reasons, smokers and
      ex-smokers both report peer pressure as the primary reason for starting to smoke,
      and the main reason smokers continue to smoke is because they are addicted. The
      best thing reported about smoking was that it relieves stress, and the worst
      thing reported about smoking was the smell. Several suggestions are made for
      future interventions targeted toward college students.

PMID- 15255160
TI  - Standardized mortality ratios by region of residence, Israel, 1987-1994: a tool
      for public health policy.
AB  - BACKGROUND: Standardized mortality ratios (SMRs) are used internationally to
      compare health status across regions and to identify high risk areas for
      investigation of specific diseases, for funding determination, and for planning
      purposes. OBJECTIVE: To ascertain regional differences in SMRs by sub-District in
      Israel for 1987-1994. METHOD: The indirect method of standardization of mortality
      rates with adjustment for age, gender, and continent of birth was used to
      calculate SMRs by major cause of death, by sub-District of residence for the
      Jewish population of Israel. RESULTS: SMRs for all causes of death ranged from
      regions with low rates (Petah Tikva, Sharon, Rehovot, Ashkelon, and Jerusalem) to
      those with high rates (Zefat/Golan, Hadera, Yizreel, Ramla, Haifa, Tel Aviv, and
      Be'er Sheva) (all p<0.0001). Zefat's SMRs are elevated for acute myocardial
      infarction, stroke, diabetes, and motor vehicle accidents (MVAs). Haifa's SMRs
      are high for all cardiovascular diseases, liver disease, MVAs, and lung cancer.
      Be'er Sheva residents had high SMRs for diabetes, liver disease, MVAs, some
      categories of cardiovascular disease, cervical cancer, and homicide. Yizreel had
      high SMRs for diabetes, hypertension, stroke, liver disease, and MVAs. Tel Aviv
      had elevated SMRs for septicemia, acute MI, perinatal causes, and colon, lung and
      breast cancer. Jerusalem (p<0.0001) and Kinneret residents (p<0.05) had low SMRs
      for everything except congenital anomalies. CONCLUSIONS: Regional SMR
      differences, adjusted for age, gender, and ethnicity, may be due to
      socioeconomic, nutritional, environmental, occupational, or health care factors.
      SMRs provide a tool to identify regions for epidemiological investigation and
      priorities for preventive interventions. Regional health monitoring should be
      undertaken routinely on mortality data, as well as other national databases, as
      part of national health monitoring.

PMID- 15255161
TI  - Primary care physicians shortage: a Korean example.
AB  - BACKGROUND: A mismatch in the demand and supply of primary care physicians could
      give rise to a disorganization of the health care system and public confusion
      about health care access. There is much evidence in Korea of the existence of a
      primary care physician shortage. The appropriate required ratio of primary care
      physicians to the total number of physicians is estimated by analyzing data for
      primary care insurance consumption in Korea. METHODS: Sums of primary care
      expenditure and claims were calculated to estimate the need for primary care
      physicians by analyzing the nationwide health insurance claims data of the Korean
      National Medical Insurance Management Corporation (KNMIMC) between the years 1989
      1998. RESULTS: The total number of physicians increased 183% from 1989 to 1998.
      However, the number of primary care physicians including general physicians,
      family physicians, general internists, and general pediatricians showed an
      increase of only 169% in those 10 years. The demand for primary care physicians
      reaches at least 58.6%, and up to 83.7%, of the total number of physicians in
      Korea. However, the number of primary care physicians comprises up to 22.0% of
      the total number of active physicians during the same research period, which
      showed a large gap between demand and supply of primary care physicians in Korea.
      CONCLUSIONS: To provide high quality care overall, a balanced supply of primary
      care physicians and specialists is required, based on the nation's demand for
      health services.

PMID- 15255162
TI  - Overview and state of the art in the management of lung cancer.
AB  - Lung cancer is a major health problem worldwide. Non-small-cell lung cancer
      (NSCLC) accounts for 80% to 85% of all lung cancers, while small-cell lung cancer
      (SCLC) accounts for 15% to 20% of cases. For early-stage and locally advanced
      NSCLC (stages I through III), a multimodality treatment approach is appropriate
      because it improves survival. Combination chemotherapy is currently the standard
      treatment for good performance patients with metastatic disease. Elderly patients
      (> or = 70 years) with metastatic NSCLC also benefit from treatment. In SCLC,
      concurrent radiation therapy and chemotherapy is the standard for limited
      disease, while chemotherapy is the treatment for extensive disease. Novel
      innovative therapies, which could include molecular targeting agents, are needed
      to treat both NSCLC and SCLC.

PMID- 15255163
TI  - Topoisomerase I inhibitors in small-cell lung cancer. The Japanese experience.
AB  - Among patients with lung cancer, approximately 15% have small-cell lung cancer
      (SCLC). The clinical characteristics of SCLC tend to be more aggressive, but also
      more sensitive to chemotherapy and radiation therapy than those of non-SCLC.
      Irinotecan (Camptosar) is a derivative of camptothecin, an inhibitor of the
      nuclear enzyme topoisomerase I. Irinotecan has been shown to exhibit excellent
      antitumor activity against SCLC in monotherapy regimens and in combination with
      cisplatin. A phase III trial comparing irinotecan and cisplatin (IP) with
      etoposide and cisplatin (EP) in patients with previously untreated extensive
      stage SCLC (ED-SCLC) was conducted. Patients in the IP arm responded
      significantly better than patients in the EP arm. In the IP arm, the response
      rate was 84%, and median overall survival was 12.8 months. A phase II trial of
      irinotecan, cisplatin, and etoposide (IPE) administered weekly (arm A) or every 4
      weeks (arm B) for ED-SCLC (JCOG 9902-DI) was also performed. In arm B, the
      response rate was 77% and the median overall survival was 12.9 months. A
      randomized trial comparing IP with IPE administered every 3 weeks in patients
      with previously untreated ED-SCLC is presently being performed in Japan.

PMID- 15255164
TI  - Irinotecan in advanced lung cancer: focus on North American trials.
AB  - New agents with improved systemic activity are needed for the treatment of lung
      cancer. Irinotecan (Camptosar) is a promising agent in advanced non-small-cell
      (NSCLC) and small-cell lung cancer (SCLC). In a Japanese phase III trial of
      advanced NSCLC, irinotecan or irinotecan/cisplatin demonstrated a significant
      survival advantage compared to the standard of vindesine/cisplatin. Similar North
      American phase III trials focusing on irinotecan's role in NSCLC are under way.
      Ongoing trials have also been launched to corroborate the significant survival
      advantage reported by a Japanese phase III trial for irinotecan/cisplatin vs
      standard etoposide/cisplatin in extensive SCLC. Current and planned trials in
      NSCLC with irinotecan in combination with gemcitabine (Gemzar), the taxanes, and
      other new agents, and thoracic radiotherapy should also provide useful clinical
      data. Moreover, trials in SCLC are investigating the rationale of combining
      irinotecan with a platinum agent as a component of chemoradiotherapy regimens.
      Promising data from these and other studies will further elucidate a role for
      irinotecan in the management of lung cancer.

PMID- 15255165
TI  - Topoisomerase I inhibitors in the combined-modality therapy of lung cancer.
AB  - Locally advanced non-small-cell lung cancer represents 30% to 40% of all
      pulmonary malignancies. Most patients will die of the disease after aggressive
      contemporary treatments. Therefore, significant improvement in therapeutic
      methods must be implemented to improve overall survival rates. The arrival of a
      new generation of chemotherapeutic agents--including the taxanes, gemcitabine
      (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar) and
      topotecan (Hycamtin)--offers the hope of significant advances in the treatment of
      lung cancer. Irinotecan and topotecan are camptothecin derivatives that inhibit
      topoisomerase I enzyme. It is believed that topoisomerase I inhibitors stabilize
      a DNA/topoisomerase I complex and interact with replication machinery to cause
      cell death. A significant amount of data demonstrates that these topoisomerase I
      inhibitors also act as radiosensitizers. With the increasing data that support
      concurrent chemoradiation treatment for malignancies, including lung cancer and
      head and neck cancers, there is an impetus to pursue the additional drugs that
      may potentially improve local control and survival. Irinotecan is undergoing
      early clinical trials in the combined-modality setting in several different
      disease sites. This paper will review the data on the role of camptothecin
      derivatives as a radiosensitizer and as a component of combined-modality therapy
      for lung cancer. It is hoped that newer treatment strategies, like the
      combination of radiation and topoisomerase I inhibitors, will have a significant
      impact on cure rates in the future.

PMID- 15255166
TI  - Management of early ovarian cancer.

PMID- 15255167
TI  - A young woman with melanoma diagnosed during pregnancy.

PMID- 15255168
TI  - Contemporary management of prostate cancer with lethal potential.
AB  - Screening for prostate cancer by determining serum prostate-specific antigen
      (PSA) levels has resulted in a stage migration such that patients with high-risk
      disease are more likely to be candidates for curative local therapy. By combining
      serum PSA, clinical stage, and biopsy information--both Gleason score and volume
      of tumor in the biopsy cores--specimen pathologic stage and patient biochemical
      disease-free survival can be estimated. This information can help patients and
      clinicians understand the severity of disease and the need for multimodal
      therapy, often in the context of a clinical trial. While the mainstays of
      treatment for local disease control are radical prostatectomy and radiation
      therapy, systemic therapy must be considered as well. A randomized trial has
      shown a survival benefit for radical prostatectomy in patients with positive
      lymph nodes who undergo immediate adjuvant androgen deprivation. Clinical trials
      are needed to clarify whether adjuvant radiation therapy after surgery confers a
      survival benefit. PSA is a sensitive marker for follow-up after local treatment
      and has proven that conventional external-beam irradiation alone is inadequate
      treatment for high-risk disease. Fortunately, the technology of radiation
      delivery has been dramatically improved with tools such as three-dimensional
      conformal radiation, intensity-modulated radiation therapy, and high-dose-rate
      brachytherapy. The further contributions of pelvic irradiation and neoadjuvant,
      concurrent, and adjuvant androgen deprivation therapy have been defined in
      clinical trials. Future management of high-risk prostate cancer may be expanded
      by clinical trials evaluating neoadjuvant and/or adjuvant chemotherapy in
      combination with androgen deprivation.

PMID- 15255169
TI  - Chronic myeloid leukemia: current status and controversies.
AB  - Until recently, the standard treatment for newly diagnosed patients with chronic
      myeloid leukemia (CML) in chronic phase who were not eligible for allogeneic stem
      cell transplant was interferon-alfa alone or in combination with low-dose
      cytarabine. Moreover, about 20% to 25% of patients who were relatively young and
      had suitable HLA-matched donors have in recent years been offered treatment by
      allogeneic stem cell transplantation, a procedure that can cure CML but is
      associated with an appreciable risk of morbidity and mortality. However,
      following the recognition in the 1980s that the p210 oncoprotein encoded by the
      BCR-ABL fusion gene on the Philadelphia chromosome had greatly enhanced tyrosine
      kinase activity and was probably the initiating event in the chronic phase of
      CML, much effort was directed toward development of drugs that would selectively
      inhibit this kinase activity. In 1998 these efforts culminated in the first
      clinical use of imatinib mesylate (Gleevec), which has since been shown to
      produce impressive results in treatment of patients with CML in chronic phase. In
      previously untreated patients, the incidence of complete cytogenetic responses
      exceeds 80%, and the majority of responses appear thus far to be durable.
      Imatinib also proved active in patients with accelerated phase and blastic phase
      disease, but in most of these cases, the benefits have been relatively short
      lived. The advent of imatinib has thus necessitated a fundamental reappraisal of
      the approach to the initial management of CML.

PMID- 15255170
TI  - Current clinical trials of HPV vaccines.

PMID- 15255171
TI  - Graft purging in autologous bone marrow transplantation: a promise not quite
      fulfilled.
AB  - Clonogenic tumor cells contained within hematopoietic stem cell (HPC) grafts may
      contribute to relapse following autologous transplantation. Graft purging
      involves either in vivo or ex vivo HPC manipulation in order to reduce the level
      of tumor cell contamination. Some phase II trials suggest that patients who
      receive purged products may have a superior transplant outcome. Phase I trials
      demonstrate the feasibility of purging methods including ex vivo graft incubation
      with chemotherapeutic drugs, monoclonal antibodies and complement, and CD34+ cell
      selection. A phase II trial in follicular non-Hodgkin's lymphoma demonstrates
      that patients who receive HPC products purged negative for bcl-2 gene
      rearrangements have a superior outcome, compared with patients who receive
      polymerase chain reaction (PCR)-positive products. This finding, however, has not
      been confirmed in a randomized trial. HPC purging has demonstrated no benefit in
      a phase III trial in myeloma. Phase II trials in acute myelogenous leukemia show
      comparable outcomes for patients who receive either purged or unpurged HPC
      grafts. Limitations of purging include possible progenitor cell loss, delayed
      engraftment, and qualitative immune defects following transplant. Data to justify
      routine use of HPC graft purging are insufficient. Phase I and II data support
      development of phase III trials of both in vivo and in vitro purging methods.

PMID- 15255172
TI  - Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1.
AB  - Gallbladder carcinoma and carcinoma of the bile ducts are relatively rare cancers
      in the United States. These cancers are often diagnosed in an advanced stage due
      to their nonspecific symptomatology and until recently have been associated with
      a dismal prognosis. Recent advances in imaging and surgical techniques along with
      emerging options in palliative chemotherapy have improved the outlook in these
      cancers. While complete surgical resection remains the only hope of cure in both
      these cancers, palliative biliary decompression and chemotherapy result in
      substantial improvement in quality of life. Part 1 of this review provides a
      relevant and comprehensive update of molecular pathology, imaging modalities, and
      surgical care. In part 2, which will appear next month, we will review palliative
      care and systemic therapy in gallbladder and biliary tract carcinomas, as well as
      the use of liver transplantation in the treatment of cholangiocarcinomas. These
      strategies are of relevance to internists as well as oncologists caring for these
      patients.

PMID- 15255173
TI  - Psychosocial interventions for children with early-onset bipolar spectrum
      disorder.
AB  - Once considered virtually nonexistent, bipolar disorder in children has recently
      received a great deal of attention from mental health professionals and the
      general public. This paper provides a current review of literature pertaining to
      the psychosocial treatment of children with early-onset bipolar spectrum disorder
      (EOBPSD). Commencing with evidence of the emerging interest in this topic, we
      then focus on terminology, the rationale for studying EOBPSD in children, current
      research and clinical progress, possible explanations for the recent increase in
      recognition, and essential issues that form the foundation of effective
      psychosocial treatment. Next we explore areas of research with direct
      implications for psychosocial treatment. These include biological and
      psychosocial risk factors associated with bipolar disorder; and the psychosocial
      treatment of adult-onset bipolar disorder, childhood-onset unipolar disorder, and
      anger management in children. Following this, we discuss treatments being
      developed and tested for children with EOBPSD. Finally, we conclude with
      recommendations for future studies needed to move the field forward.

PMID- 15255174
TI  - Clarifying parent-child reciprocities during early childhood: the early childhood
      coercion model.
AB  - Consistent with existing theory, the quality of parent-child interactions during
      early childhood affects children's social relationships and behavioral adjustment
      during middle childhood and adolescence. Harsh parenting and a propensity toward
      emotional overarousal interact very early in life to affect risk for later
      conduct problems. Less empirical work has evaluated the emergence of early
      childhood coercive parent-child reciprocities. The proposed early childhood
      coercion model describes the processes by which coercive parent-child
      reciprocities emerge. Specifically, the interaction between parenting and
      infants' propensities toward reactivity influences the development of emotion
      regulation in children and disciplinary styles in parents. Highly reactive
      children are expected to experience more difficulty learning to regulate emotions
      and to evoke harsher parenting. Through a process of mutual reinforcement, harsh
      parenting, negative emotional reactivity, and poor emotion regulation become
      coercive parent-child reciprocities during early childhood. The emergence of
      coercive parent-child interactions further diminishes children's emotional
      regulatory capacities and affects the formation of peer relationships during
      kindergarten.

PMID- 15255175
TI  - Is neighborhood context differently related to externalizing problems and
      delinquency for girls compared with boys?
AB  - Although a number of reviews of gender differences in conduct problems and
      delinquency exist, this paper fills a gap in reviewing neighborhood influences on
      gender differences in conduct problems and delinquency. These influences are
      known to be important for boys in childhood and adolescence, but cannot be
      assumed to be influential in the same manner for girls. The paper starts with
      several conceptualizations of the association between gender, neighborhoods and
      juvenile delinquency. It then addresses 4 key questions. Is residing in a
      disadvantaged neighborhood associated with problem behavior in girls? Are
      neighborhood effects independent of girls' age? Are girls in disadvantaged
      neighborhoods exposed to more risk factors than girls in advantaged
      neighborhoods? Can mediating risk factors explain gender differences in
      neighborhood effects on children's and adolescents' conduct problems and
      delinquent behavior? Answers to these questions are important to steer research
      and elucidate aspects of interventions that can be optimized for girls.

PMID- 15255176
TI  - Colon cancer: genomics and apoptotic events.
AB  - Colon cancer is the third most common cancer globally. The risk of developing
      colon cancer is influenced by a number of factors that include age and diet, but
      is primarily a genetic disease, resulting from oncogene over-expression and
      tumour suppressor gene inactivation. The induction and progression of the disease
      is briefly outlined, as are the cellular changes that occur in its progression.
      While colon cancer is uniformly amenable to surgery if detected at the early
      stages, advanced carcinomas are usually lethal, with metastases to the liver
      being the most common cause of death. Oncogenes and genetic mutations that occur
      in colon cancer are featured. The molecules and signals that act to eradicate or
      initiate the apoptosis cascade in cancer cells, are elucidated, and these include
      caspases, Fas, Bax, Bid, APC, antisense hTERT, PUMA, 15-LOX-1, ceramide,
      butyrate, tributyrin and PPARgamma, whereas the molecules which promote colon
      cancer cell survival are p53 mutants, Bcl-2, Neu3 and COX-2. Cancer therapies
      aimed at controlling colon cancer are reviewed briefly.

PMID- 15255177
TI  - Interaction of calpastatin with calpain: a review.
AB  - Calpastatin is a multiheaded inhibitor capable of inhibiting more than one
      calpain molecule. Each inhibitory domain of calpastatin has three subdomains, A,
      B, and C; A binds to domain IV and C binds to domain VI of the calpains.
      Crystallographic evidence shows that binding of C to domain VI involves
      hydrophobic interactions at a site near the first EF-hand in domain VI. Sequence
      homology suggests that binding of A to calpain domain IV also involves
      hydrophobic interactions near the EF1-hand of domain IV. Neither subdomain A nor
      C have inhibitory activity without subdomain B, but both increase the inhibitory
      activity of B. Subdomain B peptides have no inhibitory activity unless they
      contain at least 13 amino acids, and inhibitory activity increases with the
      number of amino acid residues, suggesting that inhibition requires interaction
      over a large area of the calpain molecule. Although subdomain B inhibition
      kinetically is competitive in nature, subdomain B does not seem to interact with
      the active site of the calpains directly, but may bind to domain III of the
      calpains and act to block access to the active site. It is possible that
      subdomain B binds to calpain only after it has been activated by Ca2+.

PMID- 15255179
TI  - Searching for the most effective screening system to identify cell-active
      inhibitors of beta-secretase.
AB  - The beta-secretase BACE1 is an attractive drug target for reducing the level of
      the Alzheimer's disease-promoting Abeta peptide in the brain. Whereas potent
      peptidomimetic in vitro inhibitors of BACE1 have been designed, screening
      approaches to identify cell-permeable small molecule inhibitors have had limited
      success so far. In the present minireview we summarize existing screening
      methods, discuss their scope of application in the drug discovery process and
      compare them to a novel cell-based screening system to identify BACE1 inhibitors
      by a positive yeast growth selection.

PMID- 15255178
TI  - Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway
      for the biosynthesis of peptide neurotransmitters and hormones.
AB  - Peptide neurotransmitters and hormones are synthesized as protein precursors that
      require proteolytic processing to generate smaller, biologically active peptides
      that are secreted to mediate neurotransmission and hormone actions. Neuropeptides
      within their precursors are typically flanked by pairs of basic residues, as well
      as by monobasic residues. In this review, evidence for secretory vesicle
      cathepsin L and Arg/Lys aminopeptidase as a distinct proteolytic pathway for
      processing the prohormone proenkephalin is presented. Cleavage of prohormone
      processing sites by secretory vesicle cathepsin L occurs at the NH2-terminal side
      of dibasic residues, as well as between the dibasic residues, resulting in
      peptide intermediates with Arg or Lys extensions at their NH2-termini. A
      subsequent Arg/Lys aminopeptidase step is then required to remove NH2-terminal
      basic residues to generate the final enkephalin neuropeptide. The cathepsin L and
      Arg/Lys aminopeptidase prohormone processing pathway is distinct from the
      proteolytic pathway mediated by the subtilisin-like prohormone convertases 1/3
      and 2 (PC1/3 and PC2) with carboxypeptidase E/H. Differences in specific cleavage
      sites at paired basic residue sites distinguish these two pathways. These two
      proteolytic pathways demonstrate the increasing complexity of regulatory
      mechanisms for the production of peptide neurotransmitters and hormones.

PMID- 15255180
TI  - Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion
      of the murine brain by a pneumotropic influenza A virus: implications for
      influenza-associated encephalopathy.
AB  - The infectivity and pathogenicity of influenza virus are primarily determined by
      host cellular trypsin-type processing proteases which cleave the viral membrane
      fusion glycoprotein hemagglutinin (HA). Therefore the distribution of the
      processing protease is a major determinant of the infectious organ tropism. The
      common epidemic human influenza A virus is pneumotropic and the HA processing
      proteases tryptase Clara, mini-plasmin, tryptase TC30 and ectopic anionic trypsin
      have all been isolated from mammalian airways. However, the pneumotropic
      influenza virus occasionally causes severe brain edema, particularly in children
      presenting with Reye's syndrome treated with aspirin, or in children with
      influenza-associated encephalopathy without antipyretic treatment. We have
      observed that, after influenza virus infection, the accumulation of mini-plasmin
      in the cerebral capillaries in mice with a congenital or acquired abnormality of
      mitochondrial beta-oxidation mimicking the pathological findings of Reye's
      syndrome, causes an invasion and multiplication of the pneumotropic influenza
      virus at these same locations. From these findings, we hypothesize that the
      accumulated mini-plasmin modifies the brain capillaries from a non-permissive to
      a permissive state, thereby allowing multiplication of pneumotropic influenza
      virus. In addition, mini-plasmin proteolytically destroys the blood-brain
      barrier. These pathologic findings, consistent with encephalopathy in mice with a
      systemic impairment of beta-oxidation, may have implications for human influenza
      encephalopathy.

PMID- 15255181
TI  - Protease degradomics: mass spectrometry discovery of protease substrates and the
      CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors.
AB  - The biological role of most proteases in vivo is largely unknown. Therefore, to
      develop robust techniques to analyze the protease degradome in cells and tissues
      and to elucidate their substrate degradomes we have developed a dedicated and
      complete human protease and inhibitor microarray that we have called the CLIP
      CHIP Oligonucleotides (70-mers) for identifying all 715 human proteases, inactive
      homologs and inhibitors were spotted in triplicate onto glass slides with a
      dedicated subarray containing oligonucleotides for specific human breast
      carcinoma genes. Initial analyses revealed the elevated expression of a number of
      proteases in invasive ductal cell carcinoma including ADAMTS17, carboxypeptidases
      A5 and M, tryptase-gamma and matriptase-2. Matrix metalloproteinases (MMPs)
      showed a restricted expression pattern in both normal and cancerous breast
      tissues with most expressed at low levels. However, of the several MMPs expressed
      in significant quantities, the carcinoma samples showed only slightly elevated
      amounts other than for MMP-28 which was strongly elevated. To discover new
      protease substrates we developed a novel yeast two-hybrid approach we term
      'inactive catalytic domain capture' (ICDC). Here, an inactive mutant protease
      catalytic domain lacking the propeptide was used as a yeast two hybrid bait to
      screen a human fibroblast cDNA library for interactor proteins as a substrate
      trap. Wnt-induced signaling protein-2 (WISP-2) was identified by ICDC and was
      biochemically confirmed as a new MMP substrate. In another approach we used
      isotope-coded affinity tag (ICAT) labeling with tandem mass spectrometry to
      quantitate the levels of secreted or shed extracellular proteins in MDA-MB-231
      breast carcinoma cell cultures in the presence or absence of membrane type 1-MMP
      (MT1-MMP) overexpression. By this proteomic approach we identified and
      biochemically confirmed that IL-8, the serine protease inhibitor SLPI, the death
      receptor-6, pro-TNF-alpha and CTGF are novel substrates of MT1-MMP. The utility
      and quantitative nature of ICAT with MS/MS analysis as a new screen for protease
      substrate discovery based on detection of cleaved or shed substrate products
      should be readily adaptable to other classes of protease for assessing
      proteolytic function in a cellular context.

PMID- 15255182
TI  - Human cathepsin F: expression in baculovirus system, characterization and
      inhibition by protein inhibitors.
AB  - Recombinant full-length human procathepsin F, produced in the baculovirus
      expression system, was partially processed during the purification procedure to a
      form lacking the N-terminal cystatin-like domain and activated with pepsin.
      Active cathepsin F efficiently hydrolyzed Z-FR-MCA (kcat/Km=106 mM(-1) s(-1)) and
      Bz-FVR-MCA (kcat/Km=8 mM(-1) s(-1)), whereas hydrolysis of Z-RR-MCA was very slow
      (kcat/Km<0.2 mM(-1) s(-1)). Cathepsin F was rapidly and tightly inhibited by
      cystatin C, chicken cystatin and equistatin with Ki values in the subnanomolar
      range (0.03-0.47 nM), whereas L-kininogen was a less strong inhibitor of the
      enzyme (Ki=4.7 nM). Stefin A inhibited cathepsin F slowly (kass=1.6 x 10(5) M(-1)
      s(-1)) and with a lower affinity (Ki=25 nM). These data suggest that cathepsin F
      differs from other related endopeptidases by considerably weaker inhibition by
      stefins.

PMID- 15255183
TI  - Proteinases participating in the processing and activation of prolegumain in
      primary cultured rat macrophages.
AB  - The mammalian legumain is a recently identified lysosomal cysteine proteinase
      belonging to the clan CD and homologous to plant legumain. This enzyme has the
      characteristic of specifically hydrolyzing peptide bonds after asparagine
      residues. As in the case of papain-type cysteine proteinases, legumain is
      synthesized as an inactive zymogen, and processed into a mature form localized in
      lysosomes. However, the mechanism of its activation remains unclear. In this
      study, we analyze which types of proteinases may participate in the processing of
      legumain in rat primary cultured macrophages using various proteinase inhibitors
      after 24 h treatment with Bafilomycin A1, a vacuolar ATPase inhibitor. The
      processing of legumain in macrophages was accomplished by papain-type cysteine
      proteinases other than cathepsin B.

PMID- 15255184
TI  - Human kallikrein 6 activity is regulated via an autoproteolytic mechanism of
      activation/inactivation.
AB  - Human kallikrein 6 (protease M/zyme/neurosin) is a serine protease that has been
      suggested to be a serum biomarker for ovarian cancer and may also be involved in
      pathologies of the CNS. The precursor form of human kallikrein 6 (pro-hK6) was
      overexpressed in Pichia pastoris and found to be autoprocessed to an active but
      unstable mature enzyme that subsequently yielded the inactive, self-cleavage
      product, hK6 (D81-K244). Site-directed mutagenesis was used to investigate the
      basis for the intrinsic catalytic activity and the activation mechanism of pro
      hK6. A single substitution R80 --> Q stabilized the activity of the mature
      enzyme, while substitution of the active site serine (S197 --> A) resulted in
      complete loss of hK6 proteolytic activity and facilitated protein production. Our
      data suggest that the enzymatic activity of hK6 is regulated by an
      autoactivation/autoinactivation mechanism. Mature hK6 displayed a trypsin-like
      activity against synthetic substrates and human plasminogen was identified as a
      putative physiological substrate for hK6, as specific cleavage at the plasminogen
      internal bond S460-V461 resulted in the generation of angiostatin, an endogenous
      inhibitor of angiogenesis and metastatic growth.

PMID- 15255185
TI  - Growth phase-dependent production of a cell wall-associated elastinolytic
      cysteine proteinase by Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis, a Gram-positive, coagulase-negative bacterium is a
      predominant inhabitant of human skin and mucous membranes. Recently, however, it
      has become one of the most important agents of hospital-acquired bacteriemia, as
      it has been found to be responsible for surgical wound infections developed in
      individuals with indwelling catheters or prosthetic devices, as well as in
      immunosupressed or neutropenic patients. Despite their medical significance,
      little is known about proteolytic enzymes of S. epidermidis and their possible
      contribution to the bacterium's pathogenicity; however, it is likely that they
      function as virulence factors in a manner similar to that proposed for the
      proteases of Staphylococcus aureus. Here we describe the purification of a cell
      wall-associated cysteine protease from S. epidermidis, its biochemical properties
      and specificity. A homology search using N-terminal sequence data revealed
      similarity to staphopain A (ScpA) and staphopain B (SspB), cysteine proteases
      from S. aureus. Moreover, the gene encoding S. epidermidis cysteine protease
      (Ecp) and a downstream gene coding for a putative inhibitor of the protease form
      an operon structure which resembles that of staphopain A in S. aureus. The active
      cysteine protease was detected on the bacterial cell surface as well as in the
      culture media and is apparently produced in a growth phase-dependent manner, with
      initial expression occurring in the mid-logarithmic phase. This enzyme, with
      elastinolytic properties, as well as the ability to cleave alpha1PI, fibrinogen
      and fibronectin, may possibly contribute to the invasiveness and pathogenic
      potential of S. epidermidis.

PMID- 15255186
TI  - Evidence for an interaction between leptin, T cell costimulatory antigens CD28,
      CTLA-4 and CD26 (dipeptidyl peptidase IV) in BCG-induced immune responses of
      leptin- and leptin receptor-deficient mice.
AB  - We assessed changes of the enzyme dipeptidyl peptidase IV (DPP IV, CD26) in the
      context of leptin or leptin receptor deficiency. C57BL/6 mice, Leptin-deficient
      mice (ob/ob mice, B6.V-Lep<ob>) and Leptin-receptor-deficient mice (db/db mice,
      B6.Cg-m+/+Lepr) were infected with B. Calmette-Guerin (BCG) and sacrificed three
      days later. DPP IV activity in serum was higher in ob/ob mice and in db/db mice
      than in wild-type mice. The expression of DPP IV/CD26 on splenocytes was higher
      in ob/ob mice than in wild-type animals, and lower in db/db mice, and decreased
      upon stimulation with BCG in ob/ob mice only. Several T cell antigens including
      CTLA-4 were expressed aberrantly in ob/ob and in db/db mice. Our observations
      provide evidence for a relationship between DPP IV and leptin.

PMID- 15255187
TI  - Characterisation of a highly specific, endogenous inhibitor of cysteine protease
      from Staphylococcus epidermidis, a new member of the staphostatin family.
AB  - Staphostatins, a novel family of cysteine protease inhibitors with a unique
      mechanism of action and distinct protein fold has recently been discovered. In
      this report we describe the properties of Staphylococcus epidermidis staphostatin
      A (EcpB), a new member of the family. As for other staphostatins, the recombinant
      S. epidermidis staphostatin A exerted very narrow inhibitory specificity, limited
      to cysteine protease from the same species. The closely related proteases from S.
      aureus cleaved the inhibitor at the reactive site peptide bond and inactivated
      it. The EcpB homologue, S. aureus staphostatin A (ScpB), was also susceptible to
      proteolytic cleavage at the same site by non-target cysteine proteases.
      Conversely, S. aureus staphostatin B (SspC) was resistant to such proteolysis.
      The difference in the susceptibility of individual inhibitors to proteolytic
      cleavage at the reactive site suggests subtle variations in the mechanism of
      interaction with cysteine proteases.

PMID- 15255188
TI  - Identification of cysteine protease inhibitors that belong to cystatin family 1
      in the cellular slime mold Dictyostelium discoideum.
AB  - Family 1 cystatins are cytosolic inhibitors of cysteine proteases, and they are
      conserved in higher eukaryotes. We characterized two newly identified family 1
      cystatins of the cellular slime mold Dictyostelium discoideum, cystatin A1 and
      A2. Their recombinant proteins showed specific inhibitory activity against papain
      and cathepsin B, respectively. Using specific polyclonal antibodies, we found
      that cystatin A1 is stably expressed throughout the life cycle of Dictyostelium,
      whereas cystatin A2 expression is up-regulated during the course of development.

PMID- 15255189
TI  - High molecular weight kininogen as substrate for cathepsin B.
AB  - We investigated the influence of pH and divalent cations (Zn2+, Mg2+ and Ca2+) on
      high molecular weight kininogen processing by cathepsin B. At pH 6.3, high
      molecular weight kininogen is hydrolyzed by cathepsin B at three sites generating
      fragments of 80, 60 and 40 kDa. Cathepsin B has kininogenase activity at this pH
      which is improved in the absence of divalent cations. At pH 7.35, high molecular
      weight kininogen is slightly cleaved by cathepsin B into fragments of 60 kDa, and
      cathepsin B kininogenase activity is impaired. Our results suggest that high
      molecular weight kininogen is a substrate for cathepsin B under
      pathophysiological conditions.

PMID- 15255190
TI  - 'Dipeptidyl peptidase-IV activity and/or structure homologs' (DASH) in growth
      modulated glioma cell lines.
AB  - Dipeptidyl peptidase-IV has been demonstrated to play a role in cancer biology by
      many authors. Since then, additional proteins possessing similar enzymatic
      activity have been described and their role in cancerogenesis has been
      hypothesized. To assess the complexity of these 'Dipeptidyl peptidase-IV activity
      and/or structure homologs' (DASH) in glioma cells, we have studied their presence
      in cell lines of different degree of transformation. Our results provide evidence
      of cell line-specific expression and distribution of dipeptidyl peptidase-IV
      enzyme activity-bearing molecules and their dynamics associated with cell growth
      conditions. The biologic outcome of DASH pattern of composition probably depends
      on the regulatory peptides/DASH substrates in the cellular environment.

PMID- 15255191
TI  - The crystal structure of human dipeptidyl peptidase IV (DPPIV) complex with
      diprotin A.
AB  - Dipeptidyl peptidase IV (DPPIV) is a serine protease, a member of the prolyl
      oligopeptidase (POP) family, and has been implicated in several diseases.
      Therefore, it seems important to develop selective inhibitors for human DPPIV
      (hDPPIV) that are able to control the biological function of hDPPIV. In order to
      elucidate the binding mode and substrate specificity, we determined the crystal
      structure complex of hDPPIV and diprotin A (IIe-Pro-IIe), a slowly hydrolyzed
      substrate of hDPPIV, at 2.2 A resolution. In this paper, we discuss the molecular
      interaction mechanism of diprotin A with hDPPIV based on the X-ray crystal
      structure.

PMID- 15255192
TI  - Metalloproteases with EGF, CUB, and thrombospondin-1 domains function in molting
      of Caenorhabditis elegans.
AB  - Functional analysis using RNAi was performed on eleven genes for metalloproteases
      of the M12A family in Caenorhabditis elegans and the interference of the C17G1.6
      gene (nas-37) was found to cause incomplete molting. The RNAi of the C26C6.3 gene
      (nas-36) also caused a similar molting defect but not so severely as that of the
      nas-37 gene. Both the genes encode an astacin-like metalloprotease with an
      epidermal growth factor (EGF)-like domain, a CUB domain, and a thrombospondin-1
      domain, in this order. The promoter-driven green fluorescent protein (GFP)
      expression analysis suggested that they are expressed in hypodermal cells
      throughout the larval stages and in the vulva of adult animals. In the genetic
      background of rde-1(ne219), where RNAi does not work, the molting defect caused
      by the nas-37 interference was observed when the transgenic wild-type rde-1 gene
      was expressed under the control of the dpy-7 promoter, known to be active in the
      hypodermal cells, but not under the control of the myo-3 promoter, active in the
      muscular cells. Therefore these proteases are thought to be secreted by the
      hypodermal cells and to participate in shedding of old cuticles.

PMID- 15255193
TI  - Resistance of microscopic fungi to oxidative stress.

PMID- 15255194
TI  - Involvement of K+-ATP-dependent channel in transport of monovalent thallium (Tl+)
      across the inner membrane of rat liver mitochondria.

PMID- 15255195
TI  - Thallium induces opening of the mitochondrial permeability transition pore in the
      inner membrane of rat liver mitochondria.

PMID- 15255196
TI  - ATP is a cosubstrate of the luciferase of the earthworm Fridericia heliota
      (Annelida: Clitellata: Oligochaeta: Enchytraeidae).

PMID- 15255197
TI  - The substrate specificity of the cholinesterase activity of the brain of the sea
      Pacific herring (Cluippea pallasi Val) from different populations.

PMID- 15255198
TI  - May the bacterial autolysins be the precursors of extracellular bacteriolytic
      enzymes?

PMID- 15255199
TI  - A new subfamily of the satellite DNA, CLsatIV, of the lizard Darevskia lindholmi
      (Sauria, Laceridae): structure and evolution.

PMID- 15255200
TI  - Electromechanical potentials in cortical bone (phenomenological approach).

PMID- 15255201
TI  - The study of cholinesterase activity of the liver of some fish of Caspian Sea.

PMID- 15255202
TI  - A new approach to the problem of weak magnetic fields: an effect on living
      objects.

PMID- 15255203
TI  - Energy optimality criteria in inverse problems of speech.

PMID- 15255204
TI  - Phototrophic purple bacterium Chromatium minutissimum does not synthesize
      cytokinins under optimal growth conditions.

PMID- 15255205
TI  - Genetic antiviral program against hepatitis C virus.

PMID- 15255206
TI  - The contribution of the actomyosin motor to intracellular water transport in
      Elodea canadensis.

PMID- 15255207
TI  - Alternative pathways of carotenoid biosynthesis in prokaryotes and eukaryotes.

PMID- 15255208
TI  - Patient-specific computational analysis of transvenous defibrillation: a
      comparison to clinical metrics in humans.
AB  - The goal of this study is to assess the predictive capacity of computational
      models of transvenous defibrillation by comparing the results of patient-specific
      simulations to clinical defibrillation thresholds (DFT). Nine patient-specific
      models of the thorax and in situ electrodes were created from segmented CT images
      taken after implantation of the cardioverter-defibrillator. The defibrillation
      field distribution was computed using the finite volume method. The DFTs were
      extracted from the calculated field distribution using the 95% critical mass
      criterion. The comparison between simulated and clinical DFT energy resulted in a
      rms difference of 12.4 J and a 0.05 correlation coefficient (cc). The model
      predicted DFTs were well matched to the clinical values in four patients (rms =
      1.5 J; cc = 0.84). For the remaining five patients the rms difference was 18.4 J
      with a cc = 0.85. These results suggest that computational models based soley on
      the critical mass criterion and a single value of the inexcitability threshold
      are not able to consistently predict DFTs for individual patients. However,
      inspection of the weak potential gradient field in all nine patients revealed a
      relationship between the degree of dispersion of the weak field and the clinical
      DFT, which may help identify high DFT patients.

PMID- 15255209
TI  - Controlling alternans in cardiac cells.
AB  - Electrical alternans, the alternation in action potential morphology, has been
      suggested as an important cause of potentially dangerous cardiac rhythm
      disorders. Previous studies have developed alternans control strategies based on
      the dynamics of the relationship between action potential duration and the
      previous diastolic interval. We demonstrate that alternans in a single cardiac
      cell can also be controlled by directly modifying the underlying ion channel
      dynamics. Surprisingly, we find that, for a detailed canine ventricular cell
      model, the best time to apply the control stimulus is not during the
      repolarization phase of the action potential, but rather during the early plateau
      phase, when the charge requirements are two orders of magnitude smaller. Computer
      simulations show that a single control stimulus applied during the early plateau
      can completely eliminate small-amplitude alternans, while a small number of
      stimuli can rapidly extinguish large-amplitude alternans. We have also developed
      an effective control algorithm that uses only the membrane potential as control
      input and requires no prior detailed knowledge of the cell dynamics. The study
      suggests that control strategies based on ion channel dynamics can provide new
      directions for the development of algorithms intended to control dangerous
      cardiac rhythm disorders.

PMID- 15255210
TI  - Adhesion of microfabricated particles on vascular endothelium: a parametric
      analysis.
AB  - "Smart" drug delivery systems should be selective and effective to ensure drug
      administration at the right time, at the right dosage, and anywhere in the body.
      Among the several administration routes and delivery systems that have been
      proposed, one of the most effective and promising is based on microfabricated
      particles injected directly into the blood stream. The shape, size, and material
      properties of the particles can be designed and optimized depending on the
      specific applications and targets (cell, tissue, or circulating virus). Since the
      binding affinity of particles to cells is affected by both the binding force and
      its growth rate with time, it is of great importance to consider the viscous
      response of the system. In this work, a parametric analysis is presented where
      the probability of adhesion of a microfabricated particle on the endothelium is
      expressed as a function of (i) the hemodynamic conditions, (ii) the viscoelastic
      properties of the particle and targeted cell, and (iii) density of ligands
      grafted over the particle. Criteria for the optimal design of particles are
      proposed.

PMID- 15255211
TI  - The effect of hematocrit and leukocyte adherence on flow direction in the
      microcirculation.
AB  - We sought to characterize how adherent leukocytes at the vessel wall, and the
      presence of erythrocytes, alter the streamlines (paths) of blood flow in the
      postcapillary venules. We directly visualized blood flow and leukocyte
      endothelial cell interactions in postcapillary venules located in the cremaster
      muscle of anesthetized mice. Fluid streamlines were visualized by perfusing the
      cremaster muscle tissue with 0.5-micron fluorescent beads suspended in either
      buffer or whole blood, to examine the effect that erythrocytes have on the
      directionality of flow. Acute inflammation was induced in some animals by
      pretreatment of the vessels with tumor necrosis factor-alpha. To quantify the
      flow direction, the average deflection angle was defined as a scalar metric.
      Tracer bead trajectories were measurably altered by the presence of systemic
      levels of hematocrit, determined in each animal to be about 45%. Deviation from
      undirectional flow was also found to: (i) decrease with increasing vessel
      diameter, and (ii) increase with the number of adherent leukocytes. Fluid
      streamlines in the presence or absence of leukocyte adhesion or red cells agreed
      qualitatively with those obtained from theoretical calculations of blood flow
      using multiparticle adhesive dynamics. The microscale characteristics of venular
      flow are significantly altered during inflammation or changes in local
      hematocrit.

PMID- 15255212
TI  - Sensitivity analysis of respiratory parameter estimates in the constant-phase
      model.
AB  - The constant-phase model is increasingly used to fit low-frequency respiratory
      input impedance (Zrs), highlighting the need for a better understanding of the
      use of the model. Of particular interest is the extent to which Zrs would be
      affected by changes in parameters of the model, and conversely, how reliable are
      parameters estimated from model fits to the measured Zrs. We performed
      sensitivity analysis on respiratory data from 6 adult mice, at functional
      residual capacity (FRC), total lung capacity (TLC), and during
      bronchoconstriction, obtained using a 1-25 Hz oscillatory signal. The partial
      derivatives of Zrs with respect to each parameter were first examined. The limits
      of the 95% confidence intervals, 2-dimensional pairwise and p-dimensional joint
      confidence regions were then calculated. It was found that airway resistance was
      better estimated at FRC, as determined by the confidence region limits, whereas
      tissue damping and elastance were better estimated at TLC. Airway inertance was
      poorly estimated at this frequency range, as expected. During methacholine-evoked
      pulmonary constriction, there was an increase in the uncertainty of airway
      resistance and tissue damping, but this can be compensated for by using the
      relative (weighted residuals) in preference over the absolute (unweighted
      residuals) fitting criterion. These results are consistent with experimental
      observation and physiological understanding.

PMID- 15255213
TI  - Information capacity of the corticospinal tract recordings as a neural interface.
AB  - Recording the motor output of the central nervous system from the cervical spinal
      cord was investigated as a method of generating voluntary command signals,
      potentially to be used in quadriplegic individuals. Corticospinal volleys evoked
      by motor cortex stimulation were recorded from the spinal cord surface with
      multicontact electrodes in anesthetized cats. The multicontact recordings were
      analyzed for their information-carrying capacity as a neural interface. Neural
      signals resulting from the stimulation of various points in the motor cortex were
      considered as symbols of an alphabet that were sent through a discrete
      information channel. The information capacity of this channel at the thermal
      noise level of the electrode contacts was calculated. The maximum information
      rate was 1.57 bits in a trial for a 4-symbol alphabet. The background noise that
      reduces the information rate to 50% of its maximum theoretical value was defined
      as the half-bitrate-noise-tolerance (HBR-NoiseTol) and used as a measure of
      symbol distinguishability. The HBR-NoiseTol for all trials on average was 24 +/-
      12%, 18 +/- 10%, and 15 +/- 9% for interfaces with 2-, 3-, and 4-symbol alphabets
      (n = 11 trials). The average peak-to-peak amplitude of the neural volleys was
      13.5 +/- 6.7 microV (n = 11). These results suggest that the corticospinal
      signals can be recorded with spatial selectivity from the spinal cord surface and
      thus warrant further investigation of their potential use for a spinal cord
      computer interface.

PMID- 15255214
TI  - Three-dimensional biomechanical model of benign paroxysmal positional vertigo.
AB  - A morphologically descriptive 3-canal mathematical model was developed to
      quantify the biomechanical origins of gravity-dependent semicircular canal
      responses under pathological conditions of canalithiasis and cupulolithiasis-
      conditions associated with the vestibular disorder benign paroxysmal positional
      vertigo (BPPV). The model describes the influence of displaced calcium carbonate
      debris (particles) located within the labyrinth on the time-dependent responses
      of the ampullary organs. The particles were modeled as spheres free to move in
      the canal lumen (canalithiasis) or adhered to a cupula (cupulolithiasis). The
      model predicts canal responses to the diagnostic Dix-Hallpike maneuver, and to a
      modified Epley canalith repositioning (CRP) treatment. Results for canalithiasis
      predict activation latencies and response magnitudes consistent with clinical
      observations during the Dix-Hallpike maneuver. The magnitude of the response
      evoked by the Dix-Hallpike test was primarily due to the total weight of the
      particles while the latency to peak response was due to the time required for the
      stone to move from the ampulla to the posterior apex of the canal. Results
      further illustrate the effectiveness of the Epley CRP in repositioning the
      particles and relieving the symptoms of the canalithiasis type of BPPV.

PMID- 15255215
TI  - Three-dimensional finite element modeling of human ear for sound transmission.
AB  - An accurate, comprehensive finite element model of the human ear can provide
      better understanding of sound transmission, and can be used for assessing the
      influence of diseases on hearing and the treatment of hearing loss. In this
      study, we proposed a three-dimensional finite element model of the human ear that
      included the external ear canal, tympanic membrane (eardrum), ossicular bones,
      middle ear suspensory ligaments/muscles, and middle ear cavity. This model was
      constructed based on a complete set of histological section images of a left ear
      temporal bone. The finite element (FE) model of the human ear was validated by
      comparing model-predicted ossicular movements at the stapes footplate and
      tympanic membrane with published experimental measurements on human temporal
      bones. The FE model was employed to predict the effects of eardrum thickness and
      stiffness, incudostapedial joint material, and cochlear load on acoustic
      mechanical transmission through the human ossicular chain. The acoustic
      structural coupled FE analysis between the ear canal air column and middle ear
      ossicles was also conducted and the results revealed that the peak responses of
      both tympanic membrane and stapes footplate occurred between 3000 and 4000 Hz.

PMID- 15255216
TI  - Confocal analysis of local and cellular strains in chondrocyte-agarose constructs
      subjected to mechanical shear.
AB  - Although numerous previous studies have investigated cell deformation and
      mechanotransduction within isolated chondrocytes compressed in agarose gel, no
      published studies have examined the cellular response to shear. In the present
      study, a novel experimental system has been used to apply precise magnitudes of
      simple shear strain to isolated bovine articular chondrocytes seeded in agarose.
      Specimens were gelled between porous endplates which enabled the specimen to be
      gripped within a specially designed test rig mounted on an inverted microscope.
      Confocal imaging of individual chondrocytes was used to determine the local and
      cellular shear strains at gross static shear strains up to 15%. The central
      region of the specimens experienced uniform local shear strain equal to the
      applied gross shear strain. An image analysis technique was developed to quantify
      the level of cell shear strain based upon the shear-induced rotation of a best
      fit ellipse. Cell deformation occurred such that the magnitude of the cellular
      shear strain was equal to gross shear strain. This study is the first to describe
      the deformation of isolated articular chondrocytes subjected to shear strain.
      This validated experimental system will enable future studies to examine the
      influence of shear on chondrocyte function and the associated mechanotransduction
      signalling pathways.

PMID- 15255217
TI  - Prediction of growth factor effects on engineered cartilage composition using
      deterministic and stochastic modeling.
AB  - In the design of engineered tissues, guided balance of biomaterial degeneration
      with tissue synthesis offers refined control of construct development. The
      objective of this study was to develop a mathematical model that describes the
      steady state metabolism of extracellular matrix molecules (ECM: glycosaminoglycan
      and collagen) in an engineered cartilage construct taking into account localized
      environmental changes that may arise because of the application of growth
      factors. The variable effects of growth factors were incorporated in the form of
      random noise rather than the difference in rates of synthesis and catabolism.
      Thus, the frequency of ECM accumulation for each matrix molecule in the steady
      state under the random influence of growth factor was produced relative to the
      matrix carrying capacity. Published synthesis-rate time constants and steady
      state ECM conditions from chondrocyte-polymer scaffold composites provided both
      input and validation for the model. Although the presence of growth factors in
      the presented system dynamics were considered randomized, the results described a
      positive feedback or promotional ECM synthesis at low levels of growth factors.
      While a negative feedback or inhibition of ECM synthesis was characterized at
      higher levels of growth factors. This transition phenomenon is based on a
      comparison with the results of a steady state condition in the form of a
      deterministic model and supports previous reports of guided accumulation in
      musculoskeletal, connective, and neuronal tissues.

PMID- 15255218
TI  - A calibration method used for volumetric measurement of orthodontically induced
      root resorption craters.
AB  - The aim of this study was to measure the accuracy and reproducibility of
      volumetric estimations obtained by a commercial software used to measure
      resorption craters induced by orthodontic forces. Twenty human first maxillary
      premolars were selected and divided into light and heavy force groups with 25 and
      225 g of force applied to the upper-right first premolars, respectively. The
      contralateral teeth served as controls. Samples were extracted and prepared for
      SEM stereoimaging after 28 days of force application. Volumetric measurements of
      these resorption craters were generated by the software. Standardized pyramidal
      indentations by the Vickers microhardness tester on four solid metallic
      cylindrical rods (brass, copper, stainless steel, and aluminum) similar to the
      dimensions of human premolars were used for calibration. Mathematically
      calculated volumes of these indentations were compared to volumes estimated by
      the software. The software estimated the errors of volumes of pyramidal
      indentations of the harder and softer materials to within 11 and 19%,
      respectively. Non-uniform plastic deformation that occurred in softer materials
      during indentation distorts the calculated results. The estimates obtained by the
      software even for distorted indentations caused by non-uniform plastic
      deformation have high degrees of reproducibility and accuracy.

PMID- 15255219
TI  - Control methods and the performance of the robotic testing system for human
      musculoskeletal joints.
AB  - Biomechanical testing of human musculoskeletal joints not only requires qualified
      testing machines and devices, but also needs an excellent control method to
      obtain better experimental results. In this paper, we take the human functional
      spinal unit (FSU) as an example to study how to improve the performance of the
      robotic testing system. First, the mechanical characteristics of FSU are
      described and the simplified model (rigid body-spring system) for the specimen is
      given. Because the location of the center of rotation (COR) of the specimen
      affects the performance of the system, a comprehensive analysis on the location
      of COR is carried out. The performance of the robotic testing system can also be
      improved through the improvement of the control method. Two control methods have
      been proposed in this paper: one is the improved hybrid control, the other is
      fuzzy logic control.

PMID- 15255220
TI  - Intelligent self-tuning of PID control for the robotic testing system for human
      musculoskeletal joints test.
AB  - In this paper, an intelligent proportional-integral-derivative (PID) control
      method is introduced to the robotic testing system for the biomechanical study of
      human musculoskeletal joints. For the testing system, the robot is a highly
      nonlinear and heavily coupled complicated system, and the human spinal specimen
      also demonstrates nonlinear property when undergoing testing. Although the
      conventional PID control approach is extensively used in most industrial control
      systems, it will break down for nonlinear systems, particularly for complicated
      systems that have no precise mathematical models. To overcome those difficulties,
      an intelligent fuzzy PID controller is proposed replacing the widely used
      conventional PID controllers. The fuzzy PID algorithm is outlined using the fuzzy
      set theory. The design techniques are developed based on the linguistic phase
      plane approach. The heuristic rules of syntheses are summarized into a rule-based
      expert system. Experiments are carried out and the results demonstrate the good
      performance of the robotic testing system using the proposed control method.

PMID- 15255221
TI  - Detection of postpartum depression and anxiety in a large health plan.
AB  - To determine the prevalence of diagnosed and/or treated postpartum depression and
      anxiety, records were extracted for 1 year after delivery from databases of
      outpatient diagnoses and prescriptions, for women in a health maintenance
      organization who had delivered a child from July 1997 through June 1998. For
      comparison, telephone interviews were conducted 5 to 9 months after delivery with
      random samples of women who delivered at 2 facilities from June 1998 through
      January 1999. Of the women interviewed, 11% met criteria for major depression
      during the first 4 months postpartum, and an additional 13% met criteria for
      probable depression at 5 to 9 months postpartum. In contrast 7.0% of the large
      cohort had a visit or prescription for depression. The 1-year prevalence rate for
      diagnosed and/or treated anxiety without depression was 3.8%; the rate at time of
      interview was 14.7%. Overall, less than 33% of women with substantial depression
      or anxiety symptoms were detected.

PMID- 15255222
TI  - Youth therapeutic alliance in intensive treatment settings.
AB  - Therapeutic alliance (TA), the helping relationship that develops between a
      client and clinician, has received little attention in child treatment studies
      until recently, though it is the factor found to be most predictive of clinical
      outcomes. Furthermore, TA is cited as one of the most important components to
      effective therapy according to practicing clinicians. This study examines the TA
      that develops between teacher/counselors and children in 2 settings, a partial
      hospital/day school and a wilderness camp. An important finding in this study is
      the lack of relationship between the teacher/counselor's view of TA and the
      youth's view. Moreover, this correlation does not improve according to how long
      the counselors have known or have treated the youth. The implications of this and
      other findings are discussed.

PMID- 15255223
TI  - The relationship between type of mental health provider and met and unmet mental
      health needs in a nationally representative sample of HIV-positive patients.
AB  - This study examined mental health service utilization among a nationally
      representative sample of adults with HIV and psychiatric disorders or perceived
      need for mental health services. Data are from the HIV Cost and Services
      Utilization Study (HCSUS) mental health survey (n = 1489) conducted in 1997-1998.
      Most (70%) needed mental healthcare. Of these, 30% received no mental health
      services in the previous 6 months, 16% received services from general medical
      providers (GMPs) only, and 54% used mental health specialists. Clients with
      perceived need for care were more likely to receive any mental health services
      and services from mental health specialists (versus GMPs) than clients having
      mental disorders without perceived need. More patients using specialists versus
      GMPs received psychotherapeutic medications and psychiatric hospitalizations,
      controlling for psychiatric symptom severity. The findings underscore that the
      differential mental health service provision between specialists and GMPs
      existing in the general population also is present among persons with HIV.

PMID- 15255224
TI  - Access to publicly funded methadone maintenance treatment in two western states.
AB  - This study examined individual and system characteristics associated with access
      to methadone maintenance treatment (MMT) among Medicaid-eligible adults entering
      treatment for opiate use in Oregon and Washington. Logistic regression was used
      to examine the relative contributions of predisposing, need, and enabling
      characteristics on access to MMT. Although the number of methadone admissions
      increased in both states, access rates (the percentage of opiate-using adults
      presenting for treatment who were placed on methadone) declined after 1995.
      Adults in remote counties were one fifth to one tenth as likely to be placed in a
      methadone maintenance program than those living in counties with a methadone
      clinic. Other significant barriers to access included polydrug use, legal system
      referral, residence in a group home, lack of income, and homelessness. Factors
      promoting access included prior methadone use, pregnancy, and self-referral to
      treatment. These results suggest that more can be done to expand access to
      methadone maintenance.

PMID- 15255225
TI  - Regional variation and clinical indicators of antipsychotic use in residential
      treatment: a four-state comparison.
AB  - The last decade saw an increase in psychotropic use with pediatric populations.
      Antipsychotic prescriptions are used frequently in residential treatment
      settings, with many youth receiving antipsychotics for off-label indications.
      Residential treatment data from 4 states were examined to determine if regional
      variation exists in off-label prescription and what clinicalfactors predict use.
      The study used clinical and pharmacological data collected via retrospective
      chart reviews (N = 732). The Child and Adolescent Needs and Strengths Assessment
      Mental Health Version was used to measure symptom and risk severity. Of youth
      receiving antipsychotics, 42.9% had no history of or current psychosis.
      Statistical analyses resulted in significant regional variation in use across
      states and yielded attention deficit/impulsivity, physical aggression, elopement,
      sexually abusive behavior, and criminal behavior as factors associated with
      antipsychotic prescription in nonpsychotic youth. Antipsychotic prescription is
      inconsistent across states. Off-label prescription is frequent and likelihood of
      use increases with behavior problems.

PMID- 15255226
TI  - Minor depression and rehabilitation outcome for older adults in subacute care.
AB  - During recent years, numerous studies have found an association between minor
      depressive symptoms and physical functioning for older adults recuperating from
      illness or injury Whereas earlier research has focused on the effects of minor
      depression during rehabilitation in acute or long-term settings, this study
      examined 209 patients receiving subacute physical therapy. The dependent measures
      were total score changes on the Functional Independence Measure (FIM) obtained at
      admission, discharge, and 3-month follow-up. The independent measure was minor
      depressive symptoms, as defined by the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, obtained within 5 days of admission. A binary
      logistic regression analysis was conducted with dichotomized FIM scores and the
      presence/absence of minor depressive symnptoms. The results indicated a
      statistically significant relationship between FIM score change and minor
      depression from admission to discharge, but not from discharge to follow-up.

PMID- 15255227
TI  - Confidentiality measures in mental health delivery settings: report of US health
      information managers.
AB  - Health and human service organizations are becoming increasingly liable for
      violations of patient privacy as a result of recent federal mandates at both
      state and federal levels of government. Under such conditions it would seem
      likely that managers would act to quickly implement such guidelines and mandates,
      especially in sensitive specialty areas such as mental health. This study sought
      to examine the degree and type of patient information confidentiality measures
      adopted in mental health delivery settings, through a national survey of
      accredited US health information managers. Results suggest that significant
      nonadoption of basic confidentiality measures continues to exist, despite federal
      mandates to the contrary. Further examined was the degree to which
      confidentiality management varies across adoption levels of computerized patient
      records. Significant variation was found in adoption of patient confidentiality
      measures between highly computerized and paper-based medical record functions.
      Similar levels of variation in adoption across practice settings was also
      discovered. Ramifications for national policy and patient information protection
      are discussed.

PMID- 15255228
TI  - Injection drug users and the provision of hepatitis C-related services in a
      nationwide sample of drug treatment programs.
AB  - Drug treatment facilities are important sites for providing targeted prevention
      and health services to injection drug users (IDUs) who are infected with the
      hepatitis C virus (HCV). A nationwide survey was conducted to examine whether
      differences exist in the HCV-related services provided by drug treatment programs
      that have varying proportions of IDUs among their patients. The results indicate
      that, overall, drug treatment programs with a greater proportion of IDUs offer
      significantly more HCV services as compared to programs with a smaller proportion
      of IDUs. However, important components of hepatitis C-related care, such as
      universal basic education and counseling about HCV and extensive HCV-antibody
      testing, are not yet being provided by all programs with a large proportion of
      IDUs among their patient populations.

PMID- 15255229
TI  - Reducing restraint use in a public psychiatric inpatient service.
AB  - The use of behavioral restraint in psychiatric inpatients can have physically and
      emotionally damaging effects. However, staff may view the use of restraint as a
      routine and acceptable means of maintaining safety. The goal of this project was
      to reduce the use of restraint in a public psychiatric inpatient service that
      serves an economically disadvantaged urban population. Six interventions that
      primarily involved changing staff behavior were made to reduce the use of
      restraint. These included better identification of restraint-prone patients, a
      stress/anger management group for patients, staff training on crisis
      intervention, development of a crisis response team, daily review of all
      restraints, and an incentive system for the staff. The rate of restraint use
      (number of restraints/1000 patient-days) during the 3 years before the
      interventions was compared with the rate during the 2 years after the
      interventions. There was a significant decrease in the rate of restraint use
      after the restraint reduction initiatives were implemented. The reduction was not
      accompanied by a sustained increase in incidents of assault, suicidal behavior,
      or self-injury.

PMID- 15255230
TI  - Ability of scanning laser polarimetry (GDx) to discriminate among early
      glaucomatous, ocular hypertensive and normal eyes in the Korean population.
AB  - We investigated the ability of the GDx-Nerve Fiber Analyzer (NFA) to discriminate
      between normal and early glaucomatous eyes among Korean individuals by reviewing
      the medical records of 217 consecutive subjects: 61 early glaucoma patients, 68
      ocular hypertensive patients, and 88 normal subjects. GDx parameters were
      compared using ANOVA. The Receiver Operating Characteristics (ROC) curve for each
      GDx-NFA variable was used to diagnose each parameter, and Pearson correlation
      coefficients were calculated to assess the association between GDx-NFA parameters
      and visual field indices in early glaucoma. The best GDx parameters to
      discriminate between early glaucomatous and normal subjects were the number,
      maximum modulation, ellipse modulation and inferior ratio (i.e. area under the
      ROC curve > 0.8). A value for the Number of equal to or greater than 27 was
      optimal for detecting early glaucoma, with a sensitivity of 80.3% and specificity
      of 80.7%. In addition, symmetry was positively correlated with the corrected
      pattern standard deviation (CPSD) among visual field indices in early glaucoma.

PMID- 15255231
TI  - Ultrasound biomicroscopic changes after laser iridotomy or trabeculectomy in
      angle-closure glaucoma.
AB  - This study was performed to demonstrate the ultrasound, biomicroscopic and
      dimensional changes of angle structure after laser iridotomy (LI) and primary
      trabeculectomy (PT) in primary angle-closure glaucoma (PACG). Angle-opening
      distance at a point 500 m from the scleral spur (AOD500), trabecular-iris angle
      (theta1), trabecular ciliary process distance (TCPD), ciliary process-iris angle
      (CPI), iris thickness (ID1, ID3), length of iris-lens contact distance (ILCD) and
      anterior chamber depth (ACD) were assessed before and after each procedure.
      Thirteen patients with LI and 16 with PT were prospectively enrolled. There were
      statistically significant increases in AOD500, theta1, and ILCD in both groups.
      CPI was decreased in both groups. ACD, TCPD, and iris thickness were not changed
      significantly. The changes in angle configuration after LI or PT may result more
      from alterations in aqueous pressure gradients across the iris and the changes of
      configuration were greater in the iris roots without rotation of ciliary body.
      However, we didn't find any significant differences in the changes of parameters
      between the two procedures.

PMID- 15255232
TI  - Ganglion cell death in rat retina by persistent intraocular pressure elevation.
AB  - Glaucoma is characterized by loss of retinal ganglion cells (RGCs) and their
      axons. Retrograde axoplasmic transport blockade and excitotoxicity were proposed
      to be a major cause of RGC apoptosis. We conducted this study to characterize the
      episcleral vessel cauterization glaucoma model in the rat with respect to
      decreased retrograde axoplasmic flow and subsequent apoptotic RGC death. After
      episcleral vessels were cauterized in Sprague-Dawley rats, Fluorogold was
      injected into their superior colliculi by stereotactic method. Retrograde
      axoplasmic flow and TUNEL-stained apoptotic dead cells were observed
      microscopically. Elevated intraocular pressure was maintained for up to 6 weeks
      during follow-up. Retrograde axoplasmic flow to the rat retina was significantly
      decreased. Apoptotic RGC was selectively TUNEL-stained in the retina, especially
      at the ganglion cell layers. We concluded that elevated intraocular pressure
      caused apoptotic RGC death through retrograde axoplasmic flow blockage. Further
      studies will elucidate the neuroprotection strategies in glaucoma patients.

PMID- 15255233
TI  - Effects of hyaluronic acid on the polymorphonuclear leukocyte (PMN) release of
      active oxygen and protection of bovine corneal endothelial cells from activated
      PMNs.
AB  - The goal of this study was to evaluate the function of hyaluronic acid (HA) on
      the active oxygen release from polymorphonuclear leukocytes (PMNs) and the
      protective effect of bovine corneal endothelial cells (BCEC) from activated PMNs.
      We used HA with three different molecular weights (MW 700,000, 2,000,000, and
      4,000,000) and five different concentrations (0, 0.1, 1, 2, and 3 mg/ml). We
      evaluated the amount of released superoxide from activated PMNs by using
      dismutase-inhibitable ferricytochrome C reduction. To compare the property and
      protective effect of HA with those of other viscoelastic substances, we used the
      same concentration of methylcellulose. HA suppressed superoxide release from PMNs
      and protected BCEC from activated PMNs in a dose-dependent, rather than a
      molecular weight-dependent, manner. The effect of HA reached almost a plateau at
      concentration above 2 mg/ml. However, methylcellulose, another viscoelastic
      substance, showed a similar effect. Therefore, it seems that the suppression of
      superoxide released from PMNs is not a property that is unique to HA, but is a
      general property of viscoelastic substances. Our results indicate that the action
      mechanism of HA proceeds not only through cell surface HA-receptor. We think that
      HA also acts as a physical barrier and/or a scavenger of superoxide.

PMID- 15255234
TI  - The efficacy of multi-zone cross-cylinder method for astigmatism correction.
AB  - The purpose of this study is to assess the efficacy of the multi-zone cross
      cylinder method as compared with the single method for astigmatism correction
      using LASIK. This prospective study enrolled 40 patients (52 eyes) who underwent
      the cross-cylinder method using LASIK, and 52 patients (60 eyes) who underwent
      the single method using LASIK: all patients were given a diagnosis of complex
      myopic astigmatism from the department of ophthalmology of this hospital between
      January 2002 and July 2003. Preoperatively, the mean spherical equivalent
      refraction was -3.85 +/- 1.13 D in the cross-cylinder group and -4.05 +/- 1.20 D
      in the single method group (p = 0.23). The mean cylinder was -2.05 +/- 1.58 D in
      the cross-cylinder group and -1.95 +/- 1.12 D in the single method group (p =
      0.31). 6 months after treatment the results were a mean spherical equivalent
      refraction of -0.26 +/- 0.30 D in the cross-cylinder group and -0.34 +/- 0.35 D
      in the single method group (p = 0.13). The mean cylinder was -0.38 +/- 0.29 D in
      the cross-cylinder group and -0.45 +/- 0.30 D in the single method group (p =
      0.096). There were no statistically significant differences between the two
      groups. The mean BCVA was not different from mean preoperative BCVA in both
      groups (i.e., 0.98 +/- 0.10, 0.96 +/- 0.25, p = 0.86). Postoperatively, patient
      complications that included night halo, glare and corneal haze were not noted in
      either group. In conclusion, the results of cross-cylinder method are no
      different from the single method for the correction of a complex astigmatism. In
      the future, studies will have to be conducted to assess the efficacy of the cross
      cylinder method in consideration of those factors that can affect the
      postoperative outcome.

PMID- 15255235
TI  - Long-term effect of plasmin on the vitreolysis in rabbit eyes.
AB  - The aim was to investigate the proteolytic activity of plasmin and its long-term
      complications. Plasmin was injected into the vitreous cavity of rabbits' eyes.
      Slit lamp biomicroscopy and electroretinography were performed. Rabbits were
      serially sacrificed at four months, and globes fixated and prepared for light and
      transmission electron microscopy. In both the plasmin-injected and control eyes,
      electroretinography showed a transient decrease in the amplitude, but this
      recovered to the baseline level in a week. Under the light microscope, the
      plasmin-treated eyes had a smooth retinal surface, implying separation of the
      vitreous cortex from the retina. In the control eyes, the collagen fibers
      remained on the retinal surface. By transmission electron microscopy, the plasmin
      treated eyes showed a vitreous-free retinal surface, but no vitreoretinal
      separation was observed in the control eyes. Plasmin induces a cleavage between
      the vitreous and the internal limiting membrane, with no long-term complications,
      so may be a useful pharmacologic adjunct to vitrectomy.

PMID- 15255236
TI  - Spontaneous regression of neovascularization at the disc in diabetic retinopathy.
AB  - Neovascularization at the disc (NVD) is the most serious complication in diabetic
      retinopathy, and leads to vitreous hemorrhage and tractional retinal detachment.
      We report two cases of spontaneous regression of NVD in proliferative diabetic
      retinopathy. Two men (31 and 46 years old) with diabetes had NVD in both eyes.
      They were treated with panretinal photocoagulation on the left eye first, but
      their right eyes went untreated, because they did not revisit our clinic for
      several months. Fortunately, on revisit, their neovascularization had disappeared
      a few months later in both eyes, including their untreated right eyes. We could
      not find any specific causes for the spontaneous regression of the new vessels.

PMID- 15255237
TI  - Diplopia and periorbital mass associated with Miragel buckling explant.
AB  - A 28-year-old female presented with a palpable mass lesion on the superonasal
      aspect of her right globe and she had a progressive diplopia. She had a scleral
      encircling surgery with a Miragel explant (MIRA, Waltham, Mass, USA) for the
      tractional retinal detachment associated with pars planitis 9 years previously.
      On examination, she revealed restricted eye movements of her right eye. The
      magnetic resonance imaging documented a swelling of the Miragel explant that
      mimicked a periorbital mass lesion. The Miragel explant was removed and
      fragmentation of the explant was found intraoperatively. The removed Miragel
      explant was examined by a scanning electron microscopy, and this demonstrated a
      disintergrated and swollen structural composition of the Miragel explant.
      Postoperatively, her extraocular movement was almost restored and the retina
      remained well attached. Alterations in the structural composition of the Miragel
      explant results in an excessive swelling that causes a restriction of the
      extraocular movement, and this can mimick a periorbital mass lesion.

PMID- 15255238
TI  - Bilateral spontaneous dislocation of intraocular lenses within the capsular bag
      in a retinitis pigmentosa patient.
AB  - A 45-year-old man with retinitis pigmentosa (RP), who had undergone uneventful
      extracapsular cataract extraction (ECCE) in his right eye eight years previously,
      and phacoemulsification in his left eye six years previously, had spontaneously
      dislocated intraocular lenses (IOL) within the capsular bag in both eyes one
      month apart. We removed the dislocated IOLs, and performed anterior vitrectomy
      and scleral fixation of the new IOLs. Mild contraction of the capsular bags and
      uneven distribution of the zonular remnants' clumps along the equator of the
      capsules were found by scanning electron microscopic (SEM) examination. In this
      study, we propose the correlation between RP and zonular weakness. To our
      knowledge, this is the first case report of bilateral spontaneous dislocation of
      IOLs within the capsular bag of an RP patient.

PMID- 15255239
TI  - Clinical characteristics and surgical outcomes of pseudophakic and aphakic
      retinal detachments.
AB  - We retrospectively evaluated the clinical characteristics and surgical outcomes
      of 20 pseudophakic retinal detachment (RD) patients (20 eyes) and 17 aphakic RD
      patients (17 eyes). Males were predominated in both groups. The time interval
      between cataract extraction and RD was 31 months on average in the pseudophakic
      group, 32 months with intact posterior capsule and 27 months with ruptured
      posterior capsule, and 148 months in the aphakic group. In 50% of cases with
      ruptured posterior capsule in the pseudophakic group, RD occurred within 1 year.
      The anatomic success rate was 95% in the pseudophakic group and 88% in the
      aphakic group. The most common cause of failure was the development of
      proliferative vitreoretinopathy. Visual acuities more than 20/40 after RD surgery
      were found in 13 pseudophakic (65%) and 6 aphakic (36%) eyes. Aphakic patients
      were more inclined to have silent RD than pseudophakic patients because of their
      poor visual acuity. Post-operative follow-up is required especially for the first
      1 year in cases of damaged posterior capsule due to the high incidence of RD
      during this period.

PMID- 15255240
TI  - A case of atypical progressive outer retinal necrosis after highly active
      antiretroviral therapy.
AB  - This is a report of an atypical case of progressive outer retinal necrosis (PORN)
      and the effect of highly active antiretroviral therapy (HAART) on the clinical
      course of viral retinitis in an acquired immunodeficiency syndrome (AIDS)
      patient. A 22-year-old male patient infected with human immunodeficiency virus
      (HIV) presented with unilaterally reduced visual acuity and a dense cataract.
      After cataract extraction, retinal lesions involving the peripheral and macular
      areas were found with perivascular sparing and the mud-cracked, characteristic
      appearance of PORN. He was diagnosed as having PORN based on clinical features
      and was given combined antiviral treatment. With concurrent HAART, the retinal
      lesions regressed, with the regression being accelerated by further treatment
      with intravenous acyclovir and ganciclovir. This case suggests that HAART may
      change the clinical course of PORN in AIDS patients by improving host immunity.
      PORN should be included in the differential diagnosis of acute unilateral
      cataract in AIDS patients.

PMID- 15255241
TI  - Clinical features of ocular trauma in emergency department.
AB  - This study analyzed a hospital-based study to investigate the incidence and
      clinical features of ocular traumatic emergencies in Korea. Over a 6-year period,
      1809 patients with ocular traumatic emergency each individually underwent
      clinical study including subject characteristics, type of ocular emergency,
      disease severity, etiology of ocular trauma, injury location, cause of decreased
      visual acuity, management of ocular injury, and final visual acuity. The
      homogeneity of each finding of the clinical features of ocular traumatic
      emergency was tested by an X2 test at a 95% level of certainty. During follow-up
      periods ranging from 3 days to 23 months (mean 2.0 months), the 1809 patients
      with ocular traumatic emergency, 1183 males (65.4%) and 626 females (34.6%), were
      studied. The incidence of ocular emergencies peaked in the third decade of life,
      irrespective of gender (P < 0.05). Corneal abrasion was the most common etiology
      among 1,552 (85.8%) closed injuries, and corneal laceration among 257 (14.2%)
      open injuries (P < 0.05). There were 542 cases (30%) of severe ocular injury,
      such as penetrating ocular injury, blow out fracture, and intraocular foreign
      body (IOF), and 1267 (70%) of less severe ocular injury, such as superficial
      ocular injury or contusion. The most common etiology of severe ocular injury was
      penetrating ocular injury, and that of less severe injury was corneal injury (P <
      0.05). The main causative activity of ocular injuries was work in 631 cases
      (34.9%), assault in 398 (22.0%), play in 278 (15.4%), traffic accidents in 145
      (8.0%) and sports in 128 (7.1%). Five hundred and fifty-four cases (32.5%)
      underwent surgical intervention. There was an improvement of visual acuity in 502
      cases (70.1%), no change in 122 (17.0%), and worsening in 92 (12.9%). We suggest
      that preventive educational measures be instigated at workplaces to reduce the
      incidence of ocular traumatic emergency, especially severe ocular injury.

PMID- 15255242
TI  - An atypical case of Aicardi syndrome with favorable outcome.
AB  - Aicardi syndrome is a severe congenital disorder characterized by infantile
      spasms, chorioretinal lacunae, and agenesis or hypogenesis of the corpus
      callosum. A 6 month old female had developed abnormal eye movement and seizures
      of the complex partial type and myoclonic type. MRI pictures of the patient
      revealed the presence of genu associated with agenesis of the rest of corpus
      callosum. A funduscopic examination revealed bilateral small, solitary, pale
      areas with sharp borders, some of which had minimal surrounding pigmentation
      (chorioretinal lacunae), especially clustered around the disc, and they were more
      prominent on the left side. We report here on the unusual findings of a complex
      partial seizure, myoclonic seizure and the atypical EEG finding in addition to
      the well-known characteristic clinical and imaging findings of a patient with
      Aicardi syndrome.

PMID- 15255243
TI  - A case of air-bag associated severe ocular injury.
AB  - Air-bags have received widespread support as an effective means of enhancing
      automotive safety, and they are becoming more common as standard automobile
      equipment on many cars. Although air-bag induced ocular injuries are rare, they
      present a serious concern because of the possibility of permanent damage or
      visual impairment. To date, most reports have investigated ocular injury from
      high velocity motor vehicle accidents and reports of ocular injury from low speed
      motor vehicle accidents have been rare. We describe a patient who sustained
      severe ocular injury, including periorbital fracture, hyphema, vitreous
      hemorrhage, and choroidal rupture of the macular area, due to an inflated air-bag
      in a low speed motor vehicle accident.

PMID- 15255244
TI  - Blood transfusion and increased risk for vasospasm and poor outcome after
      subarachnoid hemorrhage.
AB  - OBJECT: Nitric oxide (NO) metabolism may influence vasospasm after subarachnoid
      hemorrhage (SAH). It has been demonstrated in recent studies that erythrocytes
      carry NO for release in vessels, whereas transfused erythrocytes may lack stored
      NO. Several converging lines of evidence also indicate that blood transfusion may
      exacerbate poor outcomes in some critically ill patients. In this study the
      authors hypothesized that patients with SAH who received red blood cell (RBC)
      transfusions were at greater risk for vasospasm and poor outcome. METHODS: The
      authors retrospectively reviewed a prospective observational database, including
      hospital records, computerized tomography (CT) scans, and pre- and postoperative
      four-vessel angiograms, in which the management methods used in 441 patients
      undergoing surgery for ruptured cerebral aneurysms were described. Two hundred
      seventy patients (61.2%) received an RBC transfusion during their hospital stay.
      After adjustment for Hunt and Hess grade, SAH grade on CT scans, delay between
      rupture and surgery, smoking status, and intraoperative aneurysm rupture, a worse
      outcome was more likely in patients who received intraoperative blood (odds ratio
      [OR] 2.44, confidence interval [CI] 1.32-4.52; 120 patients). Intraoperative RBC
      transfusion did not influence subsequent angiographically confirmed vasospasm (OR
      0.92, CI 0.6-1.4). Worse outcome was observed in patients who received blood
      postoperatively (OR 1.81, CI 1.21-2.7), but not after adjustments were made for
      confounding variables (OR 1.48, CI 0.83-2.63). Angiographic vasospasm was
      observed in 217 patients and, after adjusting for confounding variables, was more
      frequent among patients who received postoperative RBC transfusion (OR 1.68, CI
      1.02-2.75). Among patients in whom angiographically confirmed vasospasm developed
      there was a tendency to have received more blood than in those with no vasospasm;
      however, a clear dose-dependent response was not observed. CONCLUSIONS:
      Development of angiographically confirmed vasospasm after SAH is associated with
      postoperative RBC transfusion and worse outcome is associated with intraoperative
      RBC transfusion. Before blood is transfused, patients with SAH should be
      carefully assessed to determine if they are symptomatic because of anemia.

PMID- 15255245
TI  - Management and outcomes in 353 surgically treated sciatic nerve lesions.
AB  - OBJECT: This is a retrospective analysis of 353 surgically treated sciatic nerve
      lesions in which injury mechanisms, location, time to surgical repair, surgical
      techniques, and functional outcomes are reported. Results are presented to
      provide guidelines for management of these injuries. METHODS: One hundred seventy
      five patients with buttock-level and 178 with thigh-level sciatic nerve injury
      were surgically treated at the Louisiana State University Health Sciences Center
      between 1968 and 1999. Buttock-level injury mechanisms included injection in 64
      patients, hip fracture/dislocation in 26, contusion in 22, compression in 19,
      gunshot wound (GSW) in 17, hip arthroplasty in 15, and laceration in 12; at the
      thigh level, GSW was the cause in 62 patients, femoral fracture in 34, laceration
      in 32, contusion in 28, compression in 12, and iatrogenic injury in 10. Patients
      with sciatic nerve divisions in which positive intraoperative nerve action
      potentials (NAPs) were found underwent neurolysis and attained at least Grade 3
      functional outcomes in 108 (87%) of 124 and in 91 (96%) of 95 buttock- and thigh
      level tibial divisions, respectively, compared with 84 (71%) of 119 and 75 (79%)
      of 95, respectively, in the peroneal divisions. For suture repair, recovery to at
      least Grade 3 occurred in eight (73%) of 11 buttock-level and in 27 (93%) of 29
      thigh-level tibial division injuries, and in three (30%) of 10 buttock-level and
      20 (69%) of 29 thigh-level peroneal division lesions. For graft repair, good
      recovery occurred in 21 (62%) of 34 and in 43 (80%) of 54 buttock- and thigh
      level tibial divisions, respectively, even in proximal repairs requiring long
      grafts, and in only nine (24%) of 37 and 22 (45%) of 49 buttock- and thigh-level
      peroneal division lesions, respectively. CONCLUSIONS: Surgical exploration and
      neurolysis after positive NAP readings, or repair with sutures or grafts after
      negative NAP results are worthwhile in selected cases.

PMID- 15255246
TI  - Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous
      malformations based on long-term follow-up data: the University of Tokyo
      experience.
AB  - OBJECT: A large number of clinical studies have been made on treatment outcomes
      of radiosurgery for arteriovenous malformations (AVMs), but the reported
      obliteration rates following this treatment vary significantly, perhaps
      reflecting the different methods and timings of the imaging studies used.
      METHODS: The authors retrospectively analyzed their experience with gamma knife
      surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65
      months), with special reference to the imaging modality used in each case. The
      calculated obliteration rates varied from 68.2 to 92%, depending on imaging
      modality and timing of evaluation. When only unquestionable imaging data such as
      demonstrations of a residual nidus on computerized tomography (CT) or magnetic
      resonance (MR) images or findings on angiograms were used in the calculation, the
      obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a
      better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p
      = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as
      determined in a multivariate analysis. Factors leading to an earlier obliteration
      of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039),
      smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p
      = 0.0201). CONCLUSIONS: After the introduction of CT and MR images into dose
      planning, the conformity and selectivity of dosimetry improved remarkably,
      although the latency intervals until obliteration were prolonged. Imaging
      outcomes for AVMs should be evaluated using data provided by longer follow-up
      periods. The timing of additional treatments for residual AVMs should be decided
      cautiously, considering the size of the AVM, the patient age and sex, and the
      history of hemorrhage before radiosurgery.

PMID- 15255247
TI  - Intracranial vertebral artery dissection with subarachnoid hemorrhage: clinical
      characteristics and outcomes in conservatively treated patients.
AB  - OBJECT: Intracranial vertebral artery (VA) dissection with subarachnoid
      hemorrhage is notorious for frequent rebleeding and a poor prognosis.
      Nevertheless, some patients survive with a good final outcome. The factors
      associated with the prognosis of this disease are not fully understood and
      appropriate treatment strategies continue to be debated. The authors
      retrospectively evaluated the clinical features of conservatively treated
      patients to elucidate the relationship between the clinical and angiographic
      characteristics of the disease and final outcomes. METHODS: This study includes
      24 patients who were treated by conservative methods between 1990 and 2000.
      Conservative treatment was chosen because of delayed diagnosis, poor clinical
      condition, or anatomical features such as bilateral lesions and contralateral VA
      hypoplasia. Of nine patients with an admission Hunt and Kosnik Grade I or II,
      eight had good outcomes (mean follow-up period 8 years and 4 months). All 15
      patients with Grade III, IV, or V died and in 10 of these the cause of death was
      rebleeding. Among the 24 patients, 14 suffered a total of 35 rebleeding episodes;
      in 10 (71.4%) of these 14 patients rebleeding occurred within 6 hours and in 13
      (93%) within 24 hours. Compared with the survivors, there was a female
      preponderance (0.022) among patients who died. These patients also had
      significantly shorter intervals between onset and hospital admission (p =
      0.0067), a higher admission Hunt and Kosnik grade (p = 0.0001), a higher
      incidence of prehospitalization (p = 0.0296) and postadmission (p = 0.0029)
      rebleeding episodes, and a higher incidence of angiographically confirmed pearl
      and-string structure of the lesion (p = 0.0049). CONCLUSIONS: In our series of
      preselected patients, poor admission neurological grade, rebleeding episode(s),
      and lesions with a pearl-and-string structure were predictive of poor outcomes.
      Our findings indicate that patients with these characteristics may be candidates
      for aggressive attempts to prevent rebleeding during the acute stage. Patients
      without these characteristics may be good candidates for conservative treatment,
      especially those who survive the acute phase without rebleeding.

PMID- 15255248
TI  - Selective disconnection of cortical venous reflux as treatment for cranial dural
      arteriovenous fistulas.
AB  - OBJECT: A single-institution series of 119 consecutive patients with a dural
      arteriovenous fistula (DAVF) and cortical venous reflux was reviewed to assess
      the overall clinical outcome of multidisciplinary management after long-term
      follow up. The selective disconnection of the cortical venous reflux compared
      with the obliteration of the entire DAVF was evaluated. METHODS: Dural
      arteriovenous fistulas in patients in this series were diagnosed between 1984 and
      2001, and treatment was instituted in 102 of them. The outcome of adequately
      treated patients was compared with that of a control group consisting of those
      with persistent cortical venous reflux and with data found in the literature. In
      cases of combined dural sinus drainage and cortical venous reflux, a novel
      treatment concept of selective disconnection of the cortical venous reflux that
      left the sinus drainage intact, and thus converted the aggressive DAVF into a
      benign lesion, was evaluated. Endovascular treatment, which was instituted
      initially in 78 patients, resulted in an obliteration or selective disconnection
      in 26 (25.5%) of 102 cases. In 70 cases (68.6%) the DAVFs were surgically
      obliterated or disconnected. In six cases (5.9%), patients were left with
      persistent cortical venous reflux. No lasting complications were noted in this
      series. Follow-up angiography confirmed a durable result in 94 (97.9%) of 96
      adequately treated cases, at a mean follow up of 27.6 months (range 1.4-138.3
      months). Selective disconnection was performed in 23 DAVFs with combined sinus
      drainage and cortical venous reflux. These patients' long-term outcomes were
      equal to those with obliterated DAVFs, and the complication rate was lower.
      CONCLUSIONS: Considering the ominous course of DAVFs with patent cortical venous
      reflux, multidisciplinary treatment of these lesions is highly effective and the
      complication rate is low. Selective disconnection provides a valid treatment
      option of DAVFs with combined dural sinus drainage and cortical venous reflux, as
      has been shown in cranial DAVFs with direct cortical venous reflux.

PMID- 15255249
TI  - Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a double
      blind 12-month evaluation study.
AB  - OBJECT: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN)
      has been established as an effective treatment for Parkinson disease (PD).
      Nevertheless, bilateral surgical procedures can be associated with frequent and
      severe complications. The aim in the present study was to assess the safety and
      efficacy of unilateral STN stimulation, and the need for a second procedure.
      METHODS: Twelve patients with PD underwent unilateral DBS of the STN and were
      followed up for 12 months. Patients were assessed at baseline and at each visit
      in a double-blind fashion by analyzing the Unified PD Rating Scale (UPDRS),
      ambulation speed, and home diaries. Levodopa-off/stimulation-on UPDRS motor
      scores were improved by 26 +/- 8% (p < 0.05, mean +/- standard deviation [SD])
      compared with the baseline levodopa-off score; there was a 50% improvement in
      contralateral features, a 17% improvement ipsilaterally, and a 36% improvement in
      axial features. The mean ambulation speed increased by 83 +/- 44% (p < 0.01, mean
      +/- SD). The medication-on time with dyskinesias was significantly reduced (p <
      0.01) and the daily levodopa dose was reduced by 19 +/- 6% (p < 0.05, mean +/-
      SD). There were no clinically significant side effects. CONCLUSIONS: Unilateral
      DBS of the STN is safe and well tolerated, and may provide sufficient benefit so
      that additional surgery is not required.

PMID- 15255250
TI  - Tremor cells in the human thalamus: differences among neurological disorders.
AB  - OBJECT: Thalamic neurons firing at frequencies synchronous with tremor are
      thought to play a critical role in the generation and maintenance of tremor. The
      authors studied the incidence and locations of neurons with tremor-related
      activity (TRA) in the thalamus of patients with varied pathological conditions
      including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS),
      and cerebellar disorders--to determine whether known differences in the
      effectiveness of thalamic stereotactic procedures for these tremors could be
      correlated to differences in the incidence or locations of TRA cells. METHODS:
      Seventy-five operations were performed in 61 patients during which 686 TRA cells
      were recorded from 440 microelectrode trajectories in the thalamus. The locations
      of the TRA cells in relation to electrophysiologically defined thalamic nuclei
      and the commissural coordinates were compared among patient groups. The authors
      found that TRA cells are present in patients with each of these disorders and
      that these cells populate several nuclei in the ventral lateral tier of the
      thalamus. There were no large differences in the locations of TRA cells among the
      different diagnostic classes, although there was a difference in the incidence of
      TRA cells in patients with PD, who had greater than 3.8 times more cells per
      thalamic trajectory than patients with ET and approximately five times more cells
      than patients with MS or cerebellar disorders. CONCLUSIONS: There was an
      increased incidence of TRA in the thalamus of patients with PD. The location of
      thalamic TRA cells in patients with basal ganglia and other tremor disorders was
      similar.

PMID- 15255251
TI  - Stimulation of the subthalamic region for essential tremor.
AB  - OBJECT: The goal of this study was to determine the safety and efficacy of
      bilateral subthalamic region stimulation in the treatment of essential tremor
      (ET). METHODS: Following induction of general anesthesia, four patients with
      disabling tremor that had proved to be refractory to pharmacotherapy underwent
      magnetic resonance imaging-guided deep brain stimulation (DBS) of the bilateral
      subthalamic region. Tremor was assessed by applying the Fahn-Tolosa-Marn Tremor
      Rating Scale at baseline and again at the 12-month follow-up examination.
      Following surgery the total tremor score improved by 80.1% (from a baseline mean
      score of 63 +/- 15.1 to a score of 11.8 +/- 3.9 at 12 months postoperatively).
      There was a significant improvement (p < 0.0001) in the mean tremor score of the
      upper limb (postural and action component) from a baseline score of 3 +/- 0.9 to
      a score of 0.5 +/- 0.5 at 12 months postoperatively. In two patients with Score 4
      head tremor complete arrest of the tremor was observed at 12 months. Motor
      function scores of the upper limb for drawing spirals, pouring water, and drawing
      lines improved significantly (p < 0.05) by 66.7, 76.9, and 58.3%, respectively.
      Handwriting improved by 68%, but this gain was not significant. The mean
      activities of daily living score at baseline was 20 +/- 3.2; there was an 88.8%
      improvement in this score to 2.3 +/- 1.5 at the 12-month evaluation. The voltage
      required for effective tremor control was low (mean 1.8 +/- 0.2 V) and, along
      with the other parameters of DBS (frequency and pulse width), did not change
      significantly over the 12-month period. Tolerance to the action component of
      tremor was not seen. There was no procedural or stimulation-related complication.
      CONCLUSIONS: Bilateral subthalamic region stimulation is effective in arresting
      tremor and head titubation, as well as functional disability in ET. Complications
      like dysarthria and disequilibrium were not seen. These patients required low
      voltages of stimulation and did not develop a tolerance to the treatment.

PMID- 15255252
TI  - Long-term outcome after epilepsy surgery for focal cortical dysplasia.
AB  - OBJECT: Reports of outcomes for surgical treatment of cortical dysplasia
      associated with epilepsy are conflicting due to the inclusion of patients with a
      wide range of malformations of cortical development. The authors report their
      experience and the long-term outcome for a subgroup of patients with the
      histopathological diagnosis of focal cortical dysplasia of Taylor. METHODS: The
      records of 22 patients with focal cortical dysplasia of Taylor (15 with the
      balloon-cell type and seven with the nonballoon-cell type) were reviewed. There
      were 11 female and 11 male patients whose mean age was 26 +/- 17.6 years (mean +/
      standard deviation [SD]) at surgery. The details of their epilepsy evaluation
      and resection were analyzed. Extent of resection was preoperatively planned using
      information obtained from long-term intracranial monitoring (15 patients) and/or
      more definitively determined by histopathologically proven clear margins during
      resection when feasible (12 patients). The mean duration of follow up was 6.3 +/-
      5.1 years (mean +/- SD, range 0.5-15.6 years). Risk factors for epilepsy were
      trauma (seven patients) or meningoencephalitis (one patient); 14 patients (64%)
      had no obvious risk factors. The mean age at seizure onset was 9.2 years and the
      mean duration of their epilepsy was 16.1 +/- 9 years. In two patients there were
      no adverse findings on magnetic resonance (MR) imaging. In 15 patients (68%), the
      epileptogenic zone identified on long-term intracranial monitoring extended
      beyond the abnormality observed on MR images. Focal resection (lesion plus
      margins) was performed in 14 patients (64%), whereas eight (36%) underwent
      partial/tailored lobectomy. Two patients underwent multiple subpial transections
      in addition to partial lesionectomy because their lesions involved the
      sensorimotor cortex. In these two, functional MR imaging confirmed a normal
      functional anatomy despite the presence of the cortical dysplasia. Eleven (92%)
      of 12 patients who underwent resection guided by histopathologically proven clear
      margins and three (43%) of seven patients who underwent histopathologically
      proven subtotal resection have remained seizure free. Evidence of clear margins
      was significantly associated with an improved seizure outcome (p = 0.003).
      Postoperatively, expected deficits included nondisabling visual field defects,
      which occurred in three patients (14%), and transient sensorimotor deficits,
      which appeared in five (23%). Two patients had meningitis, which was successfully
      treated with antibiotics. Overall, 16 patients (73%) are either seizure free (13
      patients), have rare nondisabling partial seizures (one patient), or had one
      seizure after their medication was changed (two patients). Thirteen patients
      (59%) have discontinued anticonvulsant medications or are being maintained on
      monotherapy. Of five patients (23%), two have had rare disabling seizures or
      significant reduction in their seizure frequency (three patients). One patient's
      seizures have remained the same. CONCLUSIONS: Focal cortical dysplasias are a
      distinct subgroup of malformations of cortical development and have a favorable
      outcome after resection. The epileptogenic zone often extends beyond the
      abnormality found on neuroimaging. Resection of the epileptogenic zone guided by
      histopathologically proven clear margins is associated with an improved seizure
      outcome.

PMID- 15255253
TI  - Diffusion-tensor imaging-guided tracking of fibers of the pyramidal tract
      combined with intraoperative cortical stimulation mapping in patients with
      gliomas.
AB  - OBJECT: The goal of this study was to use diffusion-tensor (DT) magnetic
      resonance (MR) imaging to track fibers combined with cortical stimulation mapping
      to delineate descending motor pathways. Subcortical localization of motor
      pathways in relation to a glioma may provide critical information to guide tumor
      resection and prevent surgical morbidity. METHODS: Eleven adult patients
      harboring gliomas underwent MR imaging 1 day prior to image-guided intraoperative
      cortical motor mapping and tumor resection. Screens depicting 27 cortical motor
      sites on a surgical navigation system were saved to launch DT imaging of fiber
      tracks of descending motor pathways. The position and organization of motor
      tracts were visualized by fiber tracking. Tracks from 16 motor stimulation sites
      followed descending pathways from the precentral gyrus, through the corona
      radiata and internal capsule, and into the cerebral peduncle. These tracks were
      also observed on DT images to diverge along crossing white matter bundles (four
      patients) and to terminate or deviate in regions of peritumoral vasogenic edema
      (five patients). CONCLUSIONS: The use of precise intraoperative cortical mapping
      information and DT images of fiber tracks can reveal the course of motor pathways
      beneath the cortex. The subcortical fiber tracks generated are consistent with
      the known anatomical course and somatotopic organization of the motor tract in
      relation to its cortical origins. Tracking fibers by using DT imaging in
      combination with functional localization has the potential to reduce surgical
      morbidity by revealing subcortical connections of the functional cortex.

PMID- 15255254
TI  - Capillary hemangioma of the central nervous system.
AB  - OBJECT: Capillary hemangiomas are benign tumors or tumorlike lesions that
      originate from blood vessels and have rarely been reported to develop in the
      brain or spinal cord. The authors summarize the clinical and histological
      features of capillary hemangiomas of the central nervous system (CNS). METHODS:
      The clinical features, imaging characteristics, and outcomes in 10 patients with
      CNS capillary hemangiomas were reviewed. Histological studies included
      immunostaining with CD31, alpha-smooth muscle actin, vascular endothelial growth
      factor, and Ki-67 antigen. Three patients with lesions in the brain presented
      with symptoms of increased intracranial pressure or seizures. Seven patients with
      lesions in the spinal cord presented with progressive sensorimotor disturbances
      of the lower limbs. Computerized tomography and magnetic resonance imaging
      demonstrated well-defined, enhancing lesions associated with marked perifocal
      edema. Angiography demonstrated hypervascular lesions, which have not recurred
      after resection. In two cases, multiple satellite lesions resolved after the
      systemic administration of steroid drugs or interferon-alpha. Histologically, all
      lesions were consistent with findings of capillary hemangioma of the skin or soft
      tissues. The CNS lesions differed significantly from other vascular neoplasms,
      such as hemangioendotheliomas, hemangiopericytomas, and hemangioblastomas.
      CONCLUSIONS: Capillary hemangiomas of the CNS are benign lesions that can be
      surgically removed and cured without adjuvant therapy.

PMID- 15255255
TI  - Prospective risk of hemorrhage in patients with vertebrobasilar nonsaccular
      intracranial aneurysm.
AB  - OBJECT: Nonsaccular intracranial aneurysms (NIAs) are characterized by dilation,
      elongation, and tortuosity of intracranial arteries. Dilemmas in management exist
      due to the limited regarding the natural history of this disease entity. The
      objective of this study was to determine the prospective risk of subarachnoid
      hemorrhage (SAH) in patients with vertebrobasilar NIAs. METHODS: All patients
      with vertebrobasilar fusiform or dolichoectatic aneurysms that had been
      radiographically demonstrated between 1989 and 2001 were identified. These
      patients' medical records were retrospectively reviewed. A prospective follow-up
      survey was sent and death certificates were requested. Based on results of
      neuroimaging studies, the maximal diameter of the involved artery, presence of
      SAH, and measurements of arterial tortuosity were recorded. Nonsaccular
      intracranial aneurysms were classified according to their radiographic
      appearance: fusiform, dolichoectatic, and transitional. Dissecting aneurysms were
      excluded. The aneurysm rupture rate was calculated based on person-years of
      follow up. Predictive factors for rupture were evaluated using univariate
      analysis (p < 0.05). One hundred fifty-nine patients, 74% of whom were men, were
      identified. The mean age at diagnosis was 64 years (range 20-87 years). Five
      patients (3%) initially presented with hemorrhage; four of these patients died
      during follow up. The mean duration of follow up was 4.4 years (692 person
      years). Nine patients (6%) experienced hemorrhage after presentation; six
      hemorrhages were definitely related to the NIA. The prospective annual rupture
      rate was 0.9% (six patients/692 person-years) overall and 2.3% in those with
      transitional or fusiform aneurysm subtypes. Evidence of aneurysm enlargement or
      transitional type of NIA was a significant predictor of lesion rupture. Six
      patients died within 1 week of experiencing lesion rupture. CONCLUSIONS: Risk of
      hemorrhage in patients harboring vertebrobasilar NIAs is more common in those
      with evidence of aneurysm enlargement or a transitional type of aneurysm and
      carries a significant risk of death.

PMID- 15255256
TI  - Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following
      subarachnoid hemorrhage in rabbits.
AB  - OBJECT: Adhesion of leukocytes and their migration into the periadventitial space
      may be critical in the pathophysiology of vasospasm following subarachnoid
      hemorrhage (SAH). The cell adhesion molecules involved in this process are
      lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1
      (CD11b/CD18), which are present on neutrophils/macrophages, and intercellular
      adhesion molecule-1 (CD54), which is present in endothelial cells. A humanized
      monoclonal antibody (mAb), Hu23F2G, targets CD11/CD18 and prevents leukocyte
      adhesion to endothelial cells. In this study, systemic administration of Hu23F2G
      prevented vasospasm in the rabbit model of SAH. METHODS: Twenty-six New Zealand
      White rabbits were injected with autologous blood into the cisterna magna to
      induce SAH, after which they were randomized to receive injections of either
      Hu23F2G (10 animals) or a placebo at 30 minutes and 24 and 48 hours after SAH
      (six animals). Control animals underwent sham operations (four animals) or SAH
      alone (six animals). The animals were killed 72 hours after SAH, their bodies
      perfused and fixed, and their basilar arteries processed for morphometric
      analysis. Peripheral white blood cells (WBCs) were counted at 72 hours. The
      percentages of lumen patency were compared using the Student t-test. The presence
      of neutrophils and macrophages was confirmed by immunohistochemical analysis in
      which a rat anti-rabbit anti-CD18 mAb and cresyl violet were used. Treatment with
      Hu23F2G resulted in the significant prevention of vasospasm. Animals treated with
      Hu23F2G had 90 +/- 7% lumen patency compared with 65 +/- 7% in the placebo group
      (p = 0.025). The percentage of lumen patency in the SAH-only group was 59 +/-
      10%. The mean WBC count was 16,300 +/- 2710/microl in the treatment group,
      compared with 7000 +/- 386/microl in the control group (p = 0.02). Administration
      of Hu23F2G produced increased numbers of WBCs in 70% of the animals treated.
      CONCLUSIONS: This study supports the concept that leukocyte-endothelial cell
      interactions play an important role in the pathophysiology of chronic vasospasm
      after SAH. Systemic therapy with an anti-CD11/CD18 mAb prevents vasospasm after
      SAH by inhibiting adhesion of neutrophils and macrophages and their migration
      into the periadventitial space.

PMID- 15255257
TI  - Inhibition of cerebral vasospasm by intracranial delivery of ibuprofen from a
      controlled-release polymer in a rabbit model of subarachnoid hemorrhage.
AB  - OBJECT: Leukocyte-endothelial cell interactions may play a role in the
      development of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH)
      because the extravasation of circulating leukocytes into the periadventitial
      space within 24 hours after the hemorrhage appears to be a critical event in this
      process. Ibuprofen is an antiinflammatory agent that inhibits the expression of
      specific cell adhesion molecules and, consequently, disrupts leukocyte
      endothelial cell interactions. The authors investigated the efficacy of ibuprofen
      delivered locally from controlled-release polymers in the rabbit basilar artery
      (BA) model of cerebral vasospasm. METHODS: Ibuprofen was incorporated into
      controlled-release ethylene-vinyl acetate copolymer (EVAc) constituting 45% of
      the resulting polymer by weight. Fifty-four New Zealand White rabbits were
      randomized to 10 groups: sham operation (seven animals); SAH only (seven
      animals); and SAH plus either empty EVAc or ibuprofen-EVAc polymer at 30 minutes
      or 6, 12, or 24 hours (five animals per group; 40 total). The rabbits were killed
      72 hours after induction of SAH, at the time of maximal vasospasm. The efficacy
      of ibuprofen in preventing vasospasm was assessed by measuring lumen patency of
      the rabbit's BAs. The intracranial controlled release of ibuprofen resulted in a
      significant inhibition of vasospasm when treatment was initiated at 30 minutes
      (patency 92.3 +/- 5.1% compared with 52.1 +/- 5.1% in animals given empty EVAc; p
      < 0.001) and 6 hours (patency 69.5 +/- 3.5% compared with 47.2 +/- 1.5% in
      animals given empty EVAc; p < 0.03) after blood deposition compared with
      treatment with empty EVAc. No effect was observed when treatment was begun at
      either 12 or 24 hours. CONCLUSIONS: Local intracranial delivery of ibuprofen
      accomplished using controlled-release polymers prevents vasospasm in the rabbit
      BA model of vasospasm when administered within 6 hours after blood exposure.

PMID- 15255258
TI  - Pharmacokinetics of controlled-release polymers in the subarachnoid space after
      subarachnoid hemorrhage in rabbits.
AB  - OBJECT: Implantation of controlled-release polymers into the subarachnoid space
      to deliver drugs for treatment of vasospasm after subarachnoid hemorrhage (SAH)
      is currently of interest. Among the issues regarding local delivery of drugs in
      the subarachnoid space, however, are the extent of diffusion and the rate of
      release of the loaded agents. In this study Evans blue dye (EBD) was loaded into
      controlled-release polymers and its pharmacokinetic properties were determined in
      vitro and in vivo by using a rabbit model of SAH. METHODS: Ethylene-vinyl acetate
      copolymer (EVAc) was loaded 40% (w:w) with EBD and its pharmacokinetics were
      spectrophotometrically determined in vitro by examining three EBD-EVAc polymers.
      Additional polymers were implanted either into the frontal lobe or into the
      cisterna magna of 16 New Zealand White rabbits. Subarachnoid hemorrhage was
      induced in eight of the animals by an injection of 1.5 ml of arterial blood into
      the cisterna magna. The animals were killed 3 or 14 days postoperatively, their
      brains and spinal cords were harvested, and samples of each were placed in
      formamide for dye extraction and quantification. Specimens were examined
      macroscopically and the concentrations of EBD were determined with the aid of a
      spectrophotometer. The EBD-EVAc polymers continuously released EBD over a 133-day
      period. The controlled release of the dye into the subarachnoid space in either
      location resulted in staining of the entire central nervous system (CNS) in
      rabbits when the polymers were placed either on the frontal lobe or in the
      cisterna magna. The EBD diffusion covered a distance of at least 40 cm. The
      presence of blood in the subarachnoid space did not interfere with the diffusion.
      CONCLUSIONS: In this study the authors define the rate and extent of diffusion of
      EBD from controlled-release polymers placed in the subarachnoid space under
      conditions of SAH. Evans blue dye diffused through the entire rabbit CNS,
      covering a distance greater than that of the longest dimension of the
      hemicircumference of the subarachnoid space around the human brain. The
      pharmacokinetic properties of EBD-EVAc polymers are comparable to those of
      antivasospasm agents that are successfully used in animal models of SAH.

PMID- 15255259
TI  - Improvement in neurological outcome after administration of atorvastatin
      following experimental intracerebral hemorrhage in rats.
AB  - OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase
      inhibitor, improves neurological functional outcome, reduces cerebral cell loss,
      and promotes regional cellular plasticity when administered after intracerebral
      hemorrhage (ICH) in rats. METHODS: Autologous blood was stereotactically injected
      into the right striatum in rats, and atorvastatin was administered orally
      beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2
      mg/kg, atorvastatin significantly reduced the severity of neurological deficit
      from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum
      was also significantly reduced in these animals. Consistent with previous study
      data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome
      or reduce the extent of injury. Histochemical stains for markers of
      synaptogenesis, immature neurons, and neuronal migration revealed increased
      labeling in the region of hemorrhage in the atorvastatin-treated rats.
      CONCLUSIONS: Analysis of the data in this study indicates that atorvastatin
      improves neurological recovery after experimental ICH and may do so in part by
      increasing neuronal plasticity.

PMID- 15255260
TI  - Bifurcation geometry and the presence of cerebral artery aneurysms.
AB  - OBJECT: The angles of arterial bifurcations are governed by principles of work
      minimization (optimality principle). This determines the relationship between the
      angle of a bifurcation and the radii of the vessels. Nevertheless, the model is
      predicated on an absence of significant communication between these branches. The
      circle of Willis changes this relationship because the vessels proximal to the
      ring of vessels have additional factors that determine work minimization compared
      with more distal branches. This must have an impact on understanding of the
      relationship between shear stress and aneurysm formation. The authors
      hypothesized that normal bifurcations of cerebral arteries beyond the circle of
      Willis would follow optimality principles of minimum work and that the presence
      of aneurysms would be associated with deviations from optimum bifurcation
      geometry. Nevertheless, the vessels participating in (or immediately proximal to)
      the circle of Willis may not follow the geometric model as it is generally
      applied and this must also be investigated. METHODS: One hundred seven
      bifurcations of the middle cerebral artery (MCA), distal internal carotid artery
      (ICA), and basilar artery (BA) were studied in 55 patients. The authors analyzed
      three-dimensional reconstructions of digital subtraction angiography images with
      respect to vessel radii and bifurcation angles. The junction exponent (that is, a
      calculated measure of the division of flow at the bifurcation) and the difference
      between the predicted optimal and observed branch angles were used as measures of
      deviation from the geometry thought best to minimize work. The mean junction
      exponent for MCA bifurcations was 2.9 +/- 1.2 (mean +/- standard deviation [SD]),
      which is close to the theoretical optimum of 3, but it was significantly smaller
      (p < 0.001; 1.7 +/- 0.8, mean +/- SD) for distal ICA bifurcations. In a
      multilevel multivariate logistic regression analysis, only the observed branch
      angles were significant independent predictors for the presence of an aneurysm.
      The odds ratio (OR) (95% confidence interval) for the presence of an aneurysm was
      3.46 (1.02-11.74) between the lowest and highest tertile of the observed angle
      between the parent vessel and the largest branch. The corresponding OR for the
      smallest branch was 48.06 (9.7-238.2). CONCLUSIONS: The bifurcation beyond the
      circle of Willis (that is, the MCA) closely approximated optimality principles,
      whereas the bifurcations within the circle of Willis (that is, the distal ICA and
      BA) did not. This indicates that the confluence of hemodynamic forces plays an
      important role in the distribution of work at bifurcations within the circle of
      Willis. In addition, the observed branch angles were predictors for the presence
      of aneurysms.

PMID- 15255261
TI  - Retinotopy with coordinates of lateral occipital cortex in humans.
AB  - OBJECT: The lateral occipital cortex in humans is known as the "extrastriate
      visual cortex." It is, however, an unexplored field of research, and the
      anatomical nomenclature for its surface has still not been standardized. This
      study was designed to investigate whether the lateral occipital cortex in humans
      has retinotopic representation. METHODS: Four right-handed patients with a
      diagnosis of intractable epilepsy from space-occupying lesions in the occipital
      lobe or epilepsy originating in the occipital lobe received permanently implanted
      subdural electrodes. Electrical cortical stimulation was applied directly applied
      to the brain through metal electrodes by using a biphasic stimulator. The
      location of each electrode was measured on a lateral skull x-ray study. Each
      patient considered a whiteboard with vertical and horizontal median lines. The
      patient was asked to look at the midpoint on the whiteboard. If a visual
      hallucination or illusion occurred, the patient recorded its outline, shape,
      color, location, and motion on white paper one tenth the size of, and with
      vertical and horizontal median lines similar to those on, the whiteboard. Polar
      angles and eccentricities of the midpoints of the phosphenes from the coordinate
      origin were measured on the paper. On stimulation of the lateral occipital lobe,
      44 phosphenes occurred. All phosphenes were circular or dotted, with a diameter
      of approximately 1 cm, except one that was like a curtain in the peripheral end
      of the upper and lower visual fields on stimulation of the parietooccipital
      region. All phosphenes appeared in the visual field contralateral to the cerebral
      hemisphere stimulated. On stimulation of the lateral occipital lobe, 22
      phosphenes moved centrifugally or toward a horizontal line. From three
      dimensional scatterplots and contour maps of the polar angles and eccentricities
      in relation to the x-ray coordinates of the electrodes, one can infer that the
      lateral occipital cortex in humans has retinotopic representation. CONCLUSIONS:
      The authors found that phosphenes induced by electrical cortical stimulation of
      the lateral occipital cortex represent retinotopy. From these results one can
      assert that visual field representation with retinotopic relation exists in the
      extrastriate visual cortex.

PMID- 15255262
TI  - Enhancement of C2-ceramide antitumor activity by small interfering RNA on X
      chromosome-linked inhibitor of apoptosis protein in resistant human glioma cells.
AB  - OBJECT: Many human glioma cells are resistant to ceramide. In this study the
      authors investigated the mechanisms of that resistance and considered ways to
      overcome it. METHODS: The authors first administered C2-ceramide (N
      acetylsphingosine) to human glioma cells from rare cell lines susceptible to C2
      ceramide (SKMG1 and U87MG) and other cell lines resistant to it (U251SP, T98G,
      SKAO2, and U251MG). Following this, the authors analyzed the statuses of
      transduction signals such as cell viability, morphological changes, caspases,
      mitochondrial membrane potential, apoptosis-inducing factor, oligonucleosomal DNA
      fragmentation, and the inhibitor of apoptosis protein (IAP) family. CONCLUSIONS:
      Ceramide resistance was found to arise from the inhibition of caspase-7 induced
      by IAPs, especially X chromosome-linked IAP (XIAP). Small interfering RNA (siRNA)
      on XIAP quenched that resistance in ceramide-resistant human glioma cells
      (U251SP, T98G, SKAO2, U251MG), indicating that a siRNA for XIAP may be a useful
      tool for overcoming the resistance to ceramide in human glioma cells.

PMID- 15255263
TI  - Life span extension and reduced neuronal death after weekly intraventricular
      cyclosporin injections in the G93A transgenic mouse model of amyotrophic lateral
      sclerosis.
AB  - OBJECT: The authors investigated whether cyclosporin A (CsA), a cyclophilin
      ligand with mitochondrial permeability transition pore-blocking and calcineurin
      inhibiting properties, affects motor function, neuronal death, and life span in
      the G93A transgenic mouse model of familial amyotrophic lateral sclerosis (FALS).
      METHODS: The G93A mice received weekly intracerebroventricular injections of CsA
      (20 microg/mouse/week) starting at the age of 65 days, and physical performance
      on an exercise wheel was monitored beginning at 84 days of age. Mice were allowed
      to survive for clinical observation of body weight, hindlimb weakness, and life
      span or until a defined end stage or were killed at 110 days of age for
      histological analysis. CONCLUSIONS: Treatment with CsA significantly delayed the
      onset of hindlimb weakness and also extended the time from its onset to
      paralysis. The overall life span of CsA-treated G93A mice was significantly
      extended, by 12% compared with vehicle-treated transgenic littermates. The CsA
      also prolonged physical performance on the exercise wheel and delayed weight
      loss. Histologically, there was significant preservation of both cervical and
      lumbar spine motor neurons and also tyrosine hydroxylase-positive dopaminergic
      substantia nigra neurons in 110-day-old CsA-treated mice compared with their
      transgenic littermates. The local administration of CsA directly into the brain
      ventricles is an effective means of central nervous system drug delivery (because
      CsA does not readily cross the blood-brain barrier), which in this study
      ameliorated clinical and neuropathological features of FALS in G93A mice. The
      remarkably low intrathecal CsA dose required for neuroprotection reduces
      potential adverse effects of systemic immunosuppression or nephrotoxicity seen
      with chronic systemic delivery of the drug.

PMID- 15255264
TI  - Effects of aminoguanidine and L-arginine methyl ester resuscitation following
      induction of fluid-percussion injury and severe controlled hemorrhagic shock in
      the rat brain.
AB  - OBJECT: In this study the authors compared the effects of both a selective
      inducible nitric oxide synthase (iNOS) inhibitor and a nonselective inhibitor on
      posttraumatic recovery and neuron survival by using a combined model of lateral
      fluid-percussion injury (FPI) and hemorrhagic shock (HS). METHODS: Male Sprague
      Dawley rats weighing 300 to 350 g underwent FPI to the brain (3.5 atm) and
      hemorrhage to a mean arterial blood pressure (MABP) of 40 mm Hg for 1 hour. Rats
      were then resuscitated during 1 hour with bolus infusions of aminoguanidine (AG)
      or nitro-L-arginine methyl ester (L-NAME). Neuronal apoptosis was determined by
      performing Nissl staining and in situ terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick-end labeling technique. Rats infused with
      AG showed a significant increase in mean survival time and cerebral tissue
      perfusion, although the MABP and nitrate/nitrite levels did not significantly
      change compared with those in L-NAME-treated rats even though both animal groups
      had been subjected to combined FPI and HS, FPI alone, or HS alone. Furthermore,
      infusion of AG also significantly decreased the number of apoptotic neurons when
      compared with the number in rats treated with L-NAME. CONCLUSIONS: The authors
      asserted that treatment with AG, which causes the inhibition of iNOS, might
      contribute to improved physiological parameters and neuronal cell survival
      following FPI and HS.

PMID- 15255266
TI  - Emergency stent placement for symptomatic acute carotid artery occlusion after
      endarterectomy. Case report.
AB  - The authors report a case of emergency carotid artery (CA) stent placement for a
      symptomatic acute CA occlusion following carotid endarterectomy (CEA). This 43
      year-old man underwent a right-sided CEA for an asymptomatic 80% CA stenosis
      detected using duplex ultrasound testing. The patient experienced hypotension and
      possibly a myocardial infarction intraoperatively and a left hemiplegia
      immediately postoperatively. He was referred to the authors' institution for
      consideration of emergency coronary intervention and evaluation of stroke. A
      computerized tomography scan of the head demonstrated subtle early ischemic
      changes in the right posterior parietal region. Cerebral angiography revealed
      occlusion of the right common CA (CCA) at the CA bifurcation. Two coronary stents
      (Magic Wall; Boston Scientific Scimed, Maple Grove, MN) were placed in tandem in
      the right CCA and internal CA (ICA), overlapping at the proximal cervical ICA.
      Complete recanalization of the CA was achieved, and the patient made a clinically
      significant recovery. Diagnostic angiography can provide important information
      about CA and intracranial circulation that will aid in the evaluation of
      postoperative stroke after CEA. Stent placement should be considered as an
      alternative method of treatment for acute CA occlusion or dissection following
      CEA.

PMID- 15255265
TI  - Pulsed holmium:yttrium-aluminum-garnet laser-induced liquid jet as a novel
      dissection device in neuroendoscopic surgery.
AB  - OBJECT: A pressure-driven continuous jet of water has been reported to be a
      feasible tool for neuroendoscopic dissection owing to its superiority at
      selective tissue dissection in the absence of thermal effects. With respect to a
      safe, accurate dissection, however, continuous water flow may not be suitable for
      intraventricular use. The authors performed experiments aimed at solving problems
      associated with continuous flow by using a pulsed holmium:yttrium-aluminum-garnet
      (Ho:YAG) laser-induced liquid jet (LILJ). They present this candidate
      neuroendoscopic LILJ dissection system, having examined its mechanical
      characteristics and evaluated its controllability both in a tissue phantom and in
      a rabbit cadaveric ventricle wall. METHODS: The LILJ generator was incorporated
      into the tip of a No. 4 French catheter so that the LILJ could be delivered via a
      neuroendoscope. Briefly, the LILJ was generated by irradiating an internally
      supplied column of physiological saline with a pulsed Ho:YAG laser (pulse
      duration time 350 microsec; laser energy 250-700 mJ/pulse) within a No. 4 French
      catheter (internal diameter 1 mm) and ejecting it from a metal nozzle (internal
      diameter 100 microm). The Ho:YAG laser energy pulses were conveyed by an optical
      fiber (core diameter 400 microm) at 3 Hz, whereas physiological saline (4 degrees
      C) was supplied at a rate of 40 ml/hour. The mechanical characteristics of the
      pulsed LILJ were investigated using high-speed photography and pressure
      measurements; thermal effects and controllability were analyzed using an
      artificial tissue model (10% gelatin of 1 mm thickness). Finally, the ventricle
      wall of a rabbit cadaver was dissected using the LILJ. Jet pressure increased in
      accordance with laser energy from 0.1 to 2 bar; this translated into a
      penetration depth of 0.08 to 0.9 mm per shot in the ventricle wall of the rabbit
      cadaver. The gelatin phantom could be cut into the desired shape without
      significant thermal effects and in the intended manner, with a good surgical
      view. CONCLUSIONS: The present results show that the pulsed LILJ has the
      potential to become a safe and reliable dissecting method for endoscopic
      procedures.

PMID- 15255267
TI  - Intentional partial coil occlusion followed by delayed clip application to wide
      necked middle cerebral artery aneurysms in patients presenting with severe
      vasospasm. Report of two cases.
AB  - The treatment of ruptured cerebral aneurysms in patients presenting with
      vasospasm remains a particular challenge. The authors treated two patients
      harboring Hunt and Hess Grade 1 subarachnoid hemorrhages from middle cerebral
      artery (MCA) aneurysms associated with severe local angiographically demonstrated
      yet asymptomatic vasospasm on presentation. Because both aneurysms had wide necks
      and were located at the MCA bifurcation, they were believed to be anatomically
      suitable for microsurgical clip application. Severe M, vasospasm was believed to
      be a relative contraindication to open surgery, however. An intentionally staged
      endovascular and microsurgical treatment strategy was planned in each patient.
      Partial coil occlusion of the aneurysmal dome was performed to prevent the lesion
      from rebleeding and was followed by balloon angioplasty of the spastic vessel.
      Early treatment of the severe spasm appeared to prevent significant delayed
      neurological ischemic deficit. Following resolution of the vasospasm, definitive
      clipping of the aneurysms was performed on Day 13 post embolization. One patient
      had a good clinical recovery and was discharged without neurological deficit. The
      other patient's hospital course was complicated by the occurrence of a
      postoperative posterior temporal infarct requiring partial temporal lobectomy,
      although she eventually had a good recovery with only a small visual field
      deficit. Based on data obtained in these two patients, one can infer that
      ruptured wide-necked MCA aneurysms associated with severe local vasospasm may
      best be treated using a staged combined treatment plan. Delayed clip application
      might be performed more safely 4 to 6 weeks postocclusion, or later, than at 2
      weeks.

PMID- 15255268
TI  - Ruptured "blisterlike" aneurysm with a pseudoaneurysm formation requiring delayed
      intervention with endovascular coil embolization. Case report.
AB  - A ruptured blisterlike aneurysm of the supraclinoid ICA rarely occurs.
      Nevertheless, it is recognized as a dangerous lesion because of the high risk of
      intraoperative bleeding associated with this lesion's wide fragile neck. There
      has been only one report of a blisterlike aneurysm treated by endosaccular
      packing after surgical wrapping. The authors describe the case of a ruptured
      blisterlike aneurysm with a pseudoaneurysm cavity, which was treated by coil
      embolization. This 63-year-old woman suffered a subarachnoid hemorrhage (SAH).
      Three cerebral aneurysms were identified on cerebral angiograms. A large saccular
      aneurysm at the ophthalmic portion of the right ICA was embolized with Guglielmi
      Detachable Coils (GDCs). Two small hemipherically shaped aneurysms on the C-2 and
      C-3 portions of the left ICA were observed conservatively. Thirteen days later,
      recurrent SAH was identified on computerized tomography scans. Angiography
      demonstrated the formation of a pseudoaneurysm from the aneurysm on the C-2
      portion of the left ICA. Endosaccular embolization with GDCs was performed 40
      days after admission. Disappearance of the pseudoaneurysm cavity and residual
      dome filling was seen immediately after the procedure. Follow-up angiography
      performed 9 months after embolization demonstrated complete obliteration of the
      aneurysm. This case illustrates that when treatment options for a blisterlike
      aneurysm with a pseudoaneurysm are unsuitable during the acute phase, coil
      embolization can be applied following progression of the lesion into a saccular
      aneurysm during the chronic stage.

PMID- 15255269
TI  - Large anterior skull base lesions in patients presenting with obstructive sleep
      apnea. Report of two cases and review of the literature.
AB  - Patients with sleep apnea often are treated by sleep disorder specialists and are
      studied in a sleep laboratory. The authors present two such patients who
      ultimately were found to harbor large benign anterior skull base lesions that
      caused their obstructive sleep apnea (OSA). The first patient had a massive
      pituitary tumor and had undergone a tracheostomy before the lesion was diagnosed.
      The second patient had a large frontoethmoidal encephalocele that was diagnosed
      at the same time as a recommendation for continuous positive airway pressure
      therapy was being considered. Such therapy in the presence of an encephalocele
      can be dangerous and even fatal. Although there are case reports of tumors
      causing OSA, nearly all of these lesions have been large pharyngeal lipomas (some
      of which were palpable in the neck during physical examination) or growth hormone
      secreting pituitary adenomas. The patients reported here were completely unaware
      of the presence of these large lesions until imaging studies and/or nasal
      endoscopy were performed. These cases illustrate the need to perform
      nasopharyngeal endoscopy and also to obtain magnetic resonance images of the head
      before prescribing therapy for OSA. Neurosurgeons must be aware that large skull
      base lesions sometimes present only with OSA.

PMID- 15255270
TI  - Brain abscess.

PMID- 15255271
TI  - Ruptured vertebral artery dissection.

PMID- 15255272
TI  - Tinnitus and auditory cortex.

PMID- 15255273
TI  - Overview of religions.
AB  - This article provides a brief overview of 9 religions: Christianity, Judaism,
      Jehovah's Witnesses, The Church of Jesus Christ of Latter-Day Saints, Christian
      Science, Islam, Hinduism, Sikhism, and Buddhism. Basic information on the
      origins, language, naming practices, diet, personal hygiene, and dress
      requirements is provided. For additional information, Web sites for each of these
      religions are also provided.

PMID- 15255274
TI  - Faith, prayer, and religious observances.
AB  - Religious and spiritual beliefs and their associated ritual or behavior play a
      major role in the lives of many people, and their observance can have critical
      impact on health care. Membership in a faith group provides an identity as well
      as support and may suggest acceptable patterns of behavior. This article
      discusses ways in which understanding of the underlying nature of religious
      belief and behavior may assist the clinician. Practices that are fundamentally
      similar among different religions and which may constrain treatment plans are
      compared. Guidelines are provided, and pointers given on key religious
      observances among major faith groups, while noting that levels of adherence and
      observance are highly personal.

PMID- 15255275
TI  - Reflections on the differences between religion and culture.
AB  - Culture may be thought of as a causal agent that affects the evolutionary process
      by uniquely human means. Religion, on the other hand, is considered a process of
      revelation and contains the concept of the "faithful" who receive the message of
      revelation. Culture permits the "self-conscious evaluation of human
      possibilities" and therefore presents a device for increasing human control over
      species change. There are dangers, however, in accepting cultural relativism
      without any constraint, such as respect for human life and dignity. In this
      article, the author attempts to clarify the boundaries between religion and
      culture and acknowledges that further research is needed on the religion/culture
      dichotomy.

PMID- 15255276
TI  - Specific health issues in ethnic minority groups.
AB  - The study of disease patterns in ethnic minority groups offers insights into the
      causation of disease. Ethnic minorities have wide variations in health conditions
      and behaviors, and stereotyping can lead to spurious assumptions in caring for
      patients. This article presents basic information relating to major illnesses
      such as cardiovascular disease, diabetes, and cancer and common health disorders
      observed among ethnic groups primarily in the United Kingdom and United States.

PMID- 15255277
TI  - End-of-life care for ethnic minority groups.
AB  - Death and dying are profound events that bring into focus important ethical and
      medical questions for all patients, whatever their cultural background. For
      ethnic minority groups and their families, specific issues or barriers may arise
      related to culturally appropriate health care practices, cultural or religious
      differences, diverse health beliefs, and access to services for care and support
      during end-of-life conditions. National policy and local initiatives in both the
      United States and the United Kingdom support the development of services that
      address the care of ethnic minorities. This article examines end-of-life care for
      ethnic minority groups.

PMID- 15255278
TI  - Cross-cultural communication in health.
AB  - Effective communication is intrinsic to the delivery of satisfactory health care.
      It is necessary to recognize that even when using a common language, serious
      communication problems may arise when cultures and their inherent understandings
      of meaning differ. This article points out instances where a common understanding
      of language is crucial.

PMID- 15255279
TI  - Insulin resistance and pre-eclampsia: a role for tumor necrosis factor-alpha?
AB  - Insulin resistance occurs in pre-eclampsia, but the cause is unknown.
      Furthermore, it is uncertain whether women destined to develop pre-eclampsia have
      a pre-existing insulin resistance or whether it is acquired with the development
      of the disease. We carried out this study to test the hypotheses that the
      increase in insulin resistance associated with pre-eclampsia is related to higher
      levels of tumor necrosis factor (TNF)-alpha, and that the increase in insulin
      resistance precedes the clinical onset of the disease. Fasting plasma samples
      were obtained from ten women who subsequently developed pre-eclampsia and ten
      normal pregnant controls at 16, 20, 24, 28, 32 and 36 weeks' gestation to measure
      circulating levels of insulin, glucose and TNF-alpha. Fasting insulin resistance
      index (FIRI) was calculated from insulin and glucose concentrations. In the
      normal controls, fasting insulin and TNF-alpha levels, and FIRI increased with
      gestation, and these were significantly greater than baseline values from 24, 28
      and 28 weeks, respectively. In the group of women who developed pre-eclampsia,
      plasma levels of insulin and the FIRI were significantly higher than baseline
      from 20 and 24 weeks, respectively, but both were significantly higher than in
      the control group at 32 and 36 weeks. The increase in TNF-alpha in the pre
      eclampsia group was significantly greater than in normal pregnant controls (p <
      0.001). However, there was no significant association between TNF-alpha levels
      and FIRI in either normal pregnancy or pregnancies developing pre-eclampsia.
      These data suggest that insulin resistance in pre-eclampsia precedes the clinical
      onset of the disease, but that it is not related to elevated levels of TNF-alpha.

PMID- 15255280
TI  - Circadian melatonin concentration rhythm is lost in pregnant women with altered
      blood pressure rhythm.
AB  - We assessed the correlation between the rhythm of melatonin concentration and
      circadian blood pressure patterns in normal and hypertensive pregnancy.
      Ambulatory 24-h blood pressure and blood samples every 4 h were monitored in 16
      primigravidae who had shown an abnormal circadian blood pressure pattern (eight
      pre-eclamptic and eight normotensive) in pregnancy and 6-12 months after
      pregnancy. The circadian rhythm was analyzed by chronobiological measures. Eight
      normotensive women with maintained blood pressure rhythm served as controls.
      During pregnancy, melatonin concentration was significantly higher in pre
      eclamptic than in normotensive women (pre-eclampsia, 29.4 +/- 1.9 pg/ml,
      normotensin, altered rhythm, 15.6 +/- 2.1; controls, 22.7 +/- 1.8; p < 0.001).
      This difference faded after pregnancy, owing to the fall observed in pre
      eclampsia (11.8 +/- 3.2 pg/ml, 9.8 +/- 2.1, and 11.1 +/- 2.0, respectively; NS).
      The rhythm of melatonin concentration was lost in all pregnant women with loss of
      blood pressure rhythm. After pregnancy, normotensive women showed a reappearance
      of both melatonin and blood pressure rhythm, whereas pre-eclamptic women showed a
      reappearance of blood pressure but not melatonin rhythm. The loss of blood
      pressure rhythm in pregnancy is consistent with the loss of melatonin
      concentration rhythm. In pre-eclamptic women, the normalization of blood pressure
      rhythm, while melatonin rhythm remained altered, suggests a temporal or causal
      priority of circadian concentration of melatonin in the determination of blood
      pressure trend.

PMID- 15255281
TI  - Cyclic mechanical stretching and interleukin-1alpha synergistically up-regulate
      prostacyclin secretion in cultured human uterine myometrial cells.
AB  - Prostacyclin (PGI2), a potent uterine smooth muscle relaxant, is postulated to be
      a major prostaglandin (PG) secreted from the human myometrium. PGI2 metabolite
      concentrations in the maternal plasma were reported to be elevated during
      pregnancy, especially during labor. Recently, we developed cultured human
      myometrial cells from pregnant women and reported that cyclic mechanical
      stretching mimicking labor increased PGI2 secretion from these cells by up
      regulating PGI2 synthase promoter activities. Since elevation of cervical/vaginal
      interleukin-1alpha (IL-1alpha) concentrations is also a characteristic feature of
      delivery, and IL-1alpha is a known stimulator of PG synthesis, we investigated a
      possible synergistic effect of cyclic mechanical stretching and IL-1alpha on PGI2
      production in cultured human myometrial cells. Treatment with IL-1alpha (10
      ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI2,
      prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha) and thromboxane A2
      (TXA2) from cultured human myometrial cells obtained from non-pregnant and
      pregnant women as well as in cultured human umbilical artery and cultured human
      coronary artery smooth muscle cells (p < 0.05 for all comparisons). However,
      labor-like cyclic mechanical stretching up-regulated IL-1alpha-augmented PGI2
      secretion from myometrial cells obtained from non-pregnant and pregnant women 2.1
      to 2.8-fold (p < 0.05 for all comparisons), but not PGE2, PGF2alpha nor TXA2.
      Moreover, such an augumentation of PGI2 secretion by cyclic mechanical stretching
      was not observed in cultured human umbilical artery nor in cultured human
      coronary artery smooth muscle cells. These results suggest that cyclic mechanical
      stretching by labor, in concert with IL-1alpha stimulation, contributes to the
      increase in myometrial PGI2 secretion during delivery.

PMID- 15255282
TI  - Laparoscopic ovarian drilling as first line of treatment in infertile women with
      polycystic ovary syndrome.
AB  - Laparoscopic ovarian drilling (LOD) is used as a first line of treatment, as a
      second line of treatment after patients have proved resistant to clomiphene or as
      a third line of treatment after failed ovulation induction with gonadotropins. We
      present the postoperative pregnancy rates of 57 women to evaluate a potential
      optimal time of LOD together with the other treatment regimens of infertile women
      with polycystic ovary syndrome (PCOS). Data on the preoperative and operative
      treatment, and background data were evaluated for their influence on pregnancy
      rates. The pregnancy rate was 61% among women with PCOS who had LOD. No
      difference was found in the clinical data between the women who became pregnant
      and those who did not. Likewise, no difference was found between the women who
      had pre- and/or postoperative medical ovulation treatment and those who had none.
      The median time to pregnancy after LOD was 135 days. LOD alone resolves
      infertility within 4-6 months in 50-60% of couples. A strategy with diagnostic
      laparoscopy and LOD as the first line of treatment of infertility in women with
      PCOS will shorten the time to pregnancy for many women, reduce the need for
      medical ovulation induction and enable diagnosis of those women with anatomic
      infertility, who can achieve pregnancy only by in vitro fertilization treatment.

PMID- 15255283
TI  - Different concentrations of interleukins in the peritoneal fluid of women with
      endometriosis: relationships with lymphocyte subsets.
AB  - The present study explored the possible relationships between immune cell subsets
      and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with
      and without endometriosis. Peritoneal fluid samples were obtained from 80 women
      while they were undergoing laparoscopy for pain, infertility, tubal ligation or
      re-anastomosis. The American Fertility Society scoring system was used to
      determine the extension of endometriosis. The peritoneal fluid mononuclear cells
      were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid
      concentrations of interleukins were measured using two ultrasensitive
      commercially available enzyme-linked imnunosorbent assay kits. Significantly
      higher peritoneal fluid IL-12 levels were found in women with moderate or severe
      endometriosis (stages III and IV) than in healthy controls (p < 0.01).
      Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid
      IL-13 concentrations than controls, independent of the severity of the disease (p
      < 0.05). Considering immune system effectors, patients with endometriosis
      presented a significantly higher peritoneal fluid CD8+/CD4+ ratio when compared
      with healthy controls. Moreover, the number of peritoneal fluid CD8+ and CD4+
      activated T cells was significantly lower in the former than in the latter group,
      independent of the endometriosis stage. Connections were observed between
      peritoneal fluid interleukins and peritoneal fluid T cells: both patients with
      endometriosis and controls presented an inverse correlation between peritoneal
      fluid activated T cells and IL-13 levels, and a direct correlation between
      peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest
      that a reciprocal modulation exists between peritoneal fluid cytokines and T
      lymphocyte subsets in patients with endometriosis.

PMID- 15255285
TI  - Pulsed estrogen exposure selectively modulates tissue response: a hypothesis.
AB  - All postmenopausal hormone replacement therapies (HTs) aim to provide a steady
      mid-follicular serum concentration of estrogen, with the exception of pulsed
      estrogen therapy, which concentrates hormone exposure in the few hours following
      administration. This alteration in the kinetics of estradiol exposure does not
      change the beneficial effect of HT on climacteric symptoms or bone loss, but does
      reduce the stimulation of the breast and uterus leading to less mastalgia and
      bleeding. The following hypothesis provides a plausible pharmacological
      explanation as to how estradiol kinetics can selectively modify tissue response.
      Pulsed estradiol exposure influences the relative abundance of estrogen receptors
      (ERs) alpha and beta, via a tissue-dependent non-genomic signaling pathway,
      resulting in selective upregulation and activation of ERbeta in breast and
      endometrium, but not in bone. In addition, pulsed estrogen exposure also
      increases local concentration of 2-methoxyestradiol, a specific estradiol
      metabolite with proven anti-tumor properties.

PMID- 15255284
TI  - Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in
      healthy postmenopausal women.
AB  - Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we
      studied the effects of ospemifene on bone turnover in postmenopausal women. This
      was a randomized, double-blind study in which 159 healthy postmenopausal women
      received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n =
      39) for 3 months. Bone resorption was assessed by measuring the urinary outputs
      of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX,
      respectively). Bone formation was assessed by measuring the levels of procollagen
      type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone
      specific alkaline phosphatase (bone ALP) in serum. All markers were studied at
      baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene
      decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4
      and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for
      all dose levels when compared to placebo). CTX values decreased in the 90 mg
      ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed
      in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3%
      (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene
      groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9
      and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo).
      These results show that ospemifene is effective in reducing bone turnover in
      postmenopausal women.

PMID- 15255286
TI  - Personal use of HRT by postmenopausal women doctors and doctors' wives in the
      north of Italy.
AB  - This study aimed to describe the prevalence of hormone replacement therapy (HRT)
      use by women doctors and doctors' wives in northern Italy, to explore the
      relationship between their personal characteristics and HRT use, and to gather
      information about the use of alternative remedies. A questionnaire was mailed to
      all physicians born between 1935 and 1955 included in the database of the Medical
      Register of Turin County (Northern Italy). The questions were meant to explore
      medical, behavioral, and professional characteristics; personal use of HRT;
      reasons for and against HRT use; side effects and use of other therapies. 56.5%
      of postmenopausal women who completed the questionnaire had used HRTand 68.3% of
      them were current users. The median duration of HRT use was 3.7 years. Only 18.5%
      of the women had used HRT for 5 years or more; in this case, HRT was started
      significantly earlier than in the other groups. More than 50% had taken oral HRT,
      while 39% had used patches; estrogens only had been taken by 21.9%. HRT users had
      a significantly lower basal body mass index and more vasomotor and dystrophic
      symptoms at menopause onset compared with non-HRT users. More women on HRT were
      in good physical health and had an active sex life. Previous breast cancer and
      family history of cardiovascular diseases were inversely associated with HRT use.
      The main reason for not taking HRT or stopping it was fear of breast cancer
      (43.7% and 34.8%, respectively); irregular bleeding and weight gain were also
      frequently reported as a reason for HRT (30% and 22%). Overall, 22% of women had
      used alternative drugs to alleviate menopausal symptoms or prevent menopause
      related diseases, mainly tibolone (21% among never HRT users and 2% among HRT
      users; p = 0.015) and phytoestrogens. The prevalence and duration of use of HRT
      by Italian physicians is consistent with the available data from other Western
      countries, and is much higher than in the general population. This is in contrast
      with the very low prevalence of use in the general population and may lead, in
      the near future, to a larger use of HRT in Italy.

PMID- 15255287
TI  - Differential expression of retinoic acid receptors in normal and malignant
      esophageal tissues.
AB  - The chemopreventive and chemotherapeutic activities of retinoids may be
      attributed to their ability to modulate growth, differentiation and apoptosis of
      epithelial cells, suppress or reverse epithelial carcinogenesis. Many of these
      effects of retinoids result from modulation of genes by two distinct classes of
      retinoid receptors: RARs and RXRs, alterations in their expression may lead to
      tumorigenesis. To determine whether alterations in expression of retinoid
      receptors are related to the development of esophageal squamous cell carcinomas
      (ESCCs), the expression of RARalpha, beta, gamma and RXRalpha was studied in 50
      untreated primary esophageal carcinomas and 19 distant normal tissues by
      immunohistochemistry. RARbeta expression was observed in 18/50 (36%) ESCCs, while
      16/19 (84%) of matched histologically normal esophageal tissues displayed RARbeta
      immunopositivity (p=0.001, 0R=3.405). Significant increase in RARalpha
      immunopositivity was observed in ESCCs (40/50; 80 %) as compared to normal
      tissues (9/19 cases; 47%) (p=0.008; 0R=2.77). RARgamma expression was observed in
      ESCCs (37/50cases; 74%) as compared to normal tissues (16/19; 84%); without
      significant difference. However, poorly differentiated esophageal cancer showed
      marked decrease in RARy immunopositivity (p=0.017; OR=6.0). Interestingly,
      increased expression of RXRalpha was observed in 43/50 (86%) ESCCs in comparison
      with (10/19; 53%) normal tissues (p=0.003; 0R=3.09). Logistic regression analysis
      revealed RARgamma-/RXRalpha+ phenotype as most significantly associated with
      dedifferentiation of the tumor (p=0.014; OR=11.0). The hallmark of the study was
      the significant increase in expression of RARalpha and RXRalpha proteins and loss
      of expression of RARbeta protein in ESCCs in comparison with the distant normal
      epithelia.

PMID- 15255288
TI  - Cytostatic anticancer drug development.
AB  - This review focuses on clinical trials and the approval process in order to
      understand the discrepancy between vibrant science and the continuing failure of
      mechanism-based anticancer drugs. CLINICAL TRIALS: Mechanistic trials in cancer
      require at least three elements: the assurance of tumor definition, knowledge of
      the natural history, and earlier intervention. Histologic identity is not a
      reliable surrogate of the functional nature or a predictor of the natural
      history. cDNA arrays and computational models have promise in improving diagnosis
      and prediction, and thereby making tailored therapy possible. The latter
      requires: the incorporation of initial and earlier rational combination therapy,
      dynamic models of disease progression, and methods to discourage the emergence of
      resistance. For cytostatics, and in early cancer, a delay in progression may
      represent a better index of survival than tumor shrinkage. APPROVAL PROCESS:
      Since mechanistic similarities may outweigh therapeutic predictions based on
      organ-and histology-defined cancer, there is a need for a revised process that
      would allow for tailored treatment and initial combination therapy to improve
      safety, efficacy, and circumvent resistance. CONCLUSION: In order to translate
      the major and immediate potential of cytostatic drugs, clinical trials and the
      approval process may need to shift to a mechanism-based framework.

PMID- 15255289
TI  - A combination therapy with copper nicotinate complex reduces the adverse effects
      of 5-fluorouracil on patients with hepatocellular carcinoma.
AB  - 5-Fluorouracil (5-FU) as chemotherapy in cases of hepatocellular carcinoma (HCC),
      was found to initiate hepatotoxic injuries, ascites, leucopenia, thrombocytopenia
      and myelosupression that limit its use. Therefore, this work was conducted to
      investigate whether the combination of copper (I)-nicotinate complex [CuCl
      (HNA)2] with 5-FU may overcome such a drug resistance. Forty-eight patients with
      HCC were therapy-naive and treated with 5-FU (12 mg/kg/day) for 5 days in 2
      cycles with 4 weeks in between. Twenty-four of them were simultaneously given
      oral doses of copper (I)-nicotinate complex (0.8 mg/kg/day) started with the 5-FU
      treatment. The combined therapy of CuCl (HNA)2 with 5-FU could improve the
      prognosis of HCC-patients. Improvement of liver function was presented by
      significant reduction of serum bilirubin (p<0.001), transaminases and alkaline
      phoshatase (p<0.05). The copper complex prevented hypoproteinaemic and
      hypoalbuminaemic effects of 5-FU and rendered the prothrombin time to its normal
      value (p<0.001). Superoxide dismutase, ceruloplasmin and immunoglobulins IgG
      showed significant increases (p<0.001), while serum copper and lipid peroxides
      were reduced (p<0.001). Thrombocytopenia, leucopenia and other myelosuppressive
      effects of 5-FU were reduced by the co-administration of CuCl (HNA)2. In
      conclusion the combination with CuCl (HNA)2 given in such a dosage schedule
      mitigated the most frequent toxicities associating 5-FU administration and
      enhanced defense mechanisms against oxidative stress.

PMID- 15255290
TI  - Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its
      inhibition by quercetin, a natural flavonoid.
AB  - Irinotecan (CPT-11) is a widely-used potent anticancer drug that inhibits
      mammalian DNA topoisomerase I, however overexpression of the ATP-binding cassette
      transporter ABCG2 can confer cancer cells resistance to SN-38, the active form of
      CPT-11. In the present study, we have examined the contribution of three variant
      forms of ABCG2 to SN-38 resistance. Exogenous expression of the Arg482 (wild
      type), Gly482, and Thr482 variants of ABCG2 conferred HEK293 cells resistance to
      SN-38 by 15.0-, 5.0-, and 5.3-fold, respectively. In plasma membrane vesicles
      prepared from the ABCG2 variant cDNA-transfected HEK293 cells, [Arg482]ABCG2
      transported SN-38 and its glucuronide conjugate in an ATP-dependent manner;
      however, only minimal transport activities were observed with the other variants
      (Gly482 and Thr482). In addition, we have screened natural flavonoids to find
      potent inhibitors of [Arg482]ABCG2. Quercetin was found to be the strongest
      inhibitor (Ki = 0.28 microM) among natural flavonoids tested in the plasma
      membrane system in this study. When [Arg482]ABCG2-transfected HEK293 cells were
      incubated with SN-38 in the presence of 20 microM quercetin, cellular resistance
      to SN-38 was partly reversed. In this context, certain flavonoid derivatives are
      considered to be good candidates for development of ABCG2 inhibitors.

PMID- 15255291
TI  - Conditionally replicating adenoviruses as anticancer agents and ways to improve
      their efficacy.
AB  - Conditionally replicating adenoviruses (CRAds) were developed as new tools for
      cancer therapy. CRAds specifically replicate in and kill cancer cells. Within a
      solid tumor mass, release of newly formed infectious particles from infected
      cancer cells allows additional cell layers to be infected and destroyed. When
      used as monotherapeutic agents, CRAds showed only limited effects in clinical
      trials. Combination studies consisting of CRAd virotherapy with chemo-, radio-or
      enzyme prodrug therapy, however, showed additive or even synergistic effects and
      encouraging results in clinical studies. Furthermore, increased CRAd efficacy
      could be achieved in preclinical models by targeting CRAd infection specifically
      to tumor cells or via insertion of therapeutic genes in the CRAd genome. In this
      review, different mechanisms to achieve CRAd specificity, the efficacy of CRAds
      in clinical trials and ways to enhance their oncolytic potency are discussed.

PMID- 15255292
TI  - Immuno-neutralization of circulating relaxin does not alter the breast cancer
      protective action of parity in MNU-treated rats.
AB  - Early pregnancy and childbirth protects women against future development of
      breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer
      incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU),
      providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD
      luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy
      factor, and that induced relaxin deficiency during rat gestation would restore
      carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched
      virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting
      mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation.
      Pregnant controls were injected with vehicle or mouse IgG on the same schedule.
      Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22.
      At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined
      daily for tumors until euthanized at age 240 days. Mammary tumor incidence and
      frequency were significantly (p<0.01) reduced and tumor latency was increased
      (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence,
      type, size and latency were similar in MCA1-treated and control primiparous rats.
      Thus, luteal relaxin does not appear to be the factor responsible for resistance
      to breast cancer.

PMID- 15255293
TI  - Selenium is effective in inducing lymphocyte progression through cell cycle in
      cancer patients: potential mechanisms for its activity.
AB  - Epidemiologic evidence in humans suggests a role for selenium in reducing cancer
      incidence and mortality. The aim of the present study was that to assess the
      ability of selenium dioxide (SeO2) to enhance the lymphocyte progression through
      the cell cycle in patients with advanced (stage IV) cancer. Ten patients (mean
      age 51.9 years, range: 32-74; M/F ratio: 3/7) with tumors at different sites were
      included in the study. The addition into culture of SeO2 1.5 microM enhanced
      significantly the progression into S phase of PBMCs isolated from cancer
      patients, whilst no significant effect was observed on PBMCs isolated from
      controls. ROS levels were significantly higher, whereas GPx activity was
      significantly lower in cancer patients than controls. Serum levels of IL-6 and
      TNFalpha were significantly higher in cancer patients than controls. Our results
      show the ability of selenium to induce a progression of PBMCs from cancer
      patients into the cell cycle, which is an essential prerequisite for the
      physiological functioning of the immune system and thus positively influence the
      immune status of advanced cancer patients. The mechanism of action of selenium
      could be to downregulate the production and release of proinflammatory cytokines,
      which have a role in cancer progression and particularly in the onset of
      cachexia.

PMID- 15255294
TI  - Phase II study of OK-432 intrapleural administration followed by systemic
      cisplatin and gemcitabine for non-small cell lung cancer with pleuritis
      carcinomatosa.
AB  - We conducted a phase II study of OK-432 intrapleural administration followed by
      systemic chemotherapy using cisplatin with gemcitabine to determine their
      combined effects on non-small cell lung cancer (NSCLC) with pleuritis
      carcinomatosa. Between December 1999 and October 2001, 15 patients were
      registered in the study. Fourteen patients had an Eastern Cooperative Oncology
      Group performance status (PS) of 1, and one patient had a PS of 2. Ten patients
      had adenocarcinoma, one had squamous cell carcinoma, and four had malignant
      mesothelioma. Patients underwent thoracocentesis and received an OK-432
      intrapleural injection. They were then treated every three weeks with
      chemotherapy consisting of 80 mg/m2 cisplatin on day 1 and 1000 mg/m2 gemcitabine
      on days 1 and 8. Thirteen patients received two or more courses of chemotherapy.
      Grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred in five, two and
      three patients, respectively. Non-hematological toxicities were mild, except for
      one patient who experienced a grade 3 elevation of transaminase and two patients
      who experienced grade 3 nausea. Of the 15 patients, one achieved partial response
      (PR), 13 a stable disease (SD) rating, and one a progressive disease (PD) rating,
      and the overall response rate was 6.7%. The median survival time was 13.5 months
      and the one-year survival rate was 60.0%. In conclusion, OK-432 intrapleural
      administration followed by cisplatin and gemcitabine systemic chemotherapy did
      not reduce patients' tumors but did prolong their survival time. A large-scale
      phase II study of the efficacy of this combination therapy is required.

PMID- 15255295
TI  - The structure of the human semilunar plica at different stages of its development
      -a morphological and morphometric study.
AB  - In this study development of the semilunar plica was examined histologycally by
      making sections through the eyes of eleven foetuses at different stages of
      gestation, two newborns and an old man. We found that in the early stages of its
      development the semilunar fold covered a bigger part of the orbit and later did
      not keep up with the growth of the eyeball and the lids. In its development three
      different kinds of germinal glands could be seen in the semilunar plica. Beside
      poorly differentiated buds of the surface epithelium which can be classified as
      rudiments of the nictitating or Harderian gland, serous glands were detected
      which could be beginnings of Krause's glands. Additionally, a new kind of plica
      gland was identified in which ductular structures, with an onion skin appearance,
      could be discriminated from mucous acini. The surface of the plica developed
      slowly by an increase in the layers of its epithelium as well as by the
      maturation of the epithelial cells from a two-layered cuboidal to a multi-layered
      cylindrical epithelium. In general the palpebral side of the plica consisted of a
      higher number of epithelial layers and more goblet cells than its bulbar side.
      Moreover, the surface of the palpebral side appeared more irregular and enlarged
      by numerous pleatings of its epithelium. The initially loose mesenchymal
      connective tissue was soon condensed by firstly an increase of the number of
      cells and later by an increase in the fibre density. In the tight collagenous
      connective tissue no elastic or reticular fibres or cartilaginous structures
      could be found. Very dense vascularization of the plica semilunaris was seen
      early in development. The blood vessels rising from the root of the plica divided
      themselves into a central and a subepithelial vascular net. Later on, some of
      them showed an enlarged lumen and were covered by a thin layer of muscle cells. A
      few unmyelinated neurofibres were found next to blood vessels and glands. Muscle
      cells could not be detected. A very dense concentration of leukocytes in the
      plica even in early intrauterine development was very striking and could be
      observed in this kind for the first time. These were mostly lymphoplasmocytic
      elements but granulocytes and macrophages could also be seen around the blood
      vessels and in the subepithelial area where they were arranged as follicles. Some
      of these cells even passed through the epithelium and could be found in the
      conjunctival fissure. The discovery of dense infiltration with both specific and
      non-specific immune cells, abundant vascularization and secretory structures
      (goblet cells and surface enlargement) in the semilunar plica suggest that it
      plays an important role as a specialized organ in human eye protection. Its
      anatomical position at the medial border of the eye supports this theory. Its
      origin from the third eyelid of the mammals could be recognized to a certain
      extent.

PMID- 15255296
TI  - The effect of bromide on the ultrastructure of rat thyrocytes.
AB  - Electron microscopic examination of thyroid tissue following administration of
      bromide to rats showed marked hypertrophy and hyperplasia in the thyrocytes,
      microfollicular rearrangement and lowered volume of colloid. The luminal surface
      of the thyrocytes showed increased size and number of microvilli, often filling
      the microlumen. Most of the nuclei were irregular in shape with unusual incisions
      and a higher density of chromatin. Proliferation of ER was seen with
      significantly dilated cisterns containing low electron density material. The
      Golgi complex was well developed and larger in rats receiving 10 mg Br/l drinking
      water (16 days) and 100 mg Br/l (16 and 66 days) than in control rats. Granules
      and small spherical structures (50-100 nm) appeared in the subapical part of the
      cytoplasm and their number increased in animals after administration of 50 mg Br
      /l (16 and 66 days), 100 mg Br-/l (16 and 66 days), 200 and 400 mg Br-/l (133
      days). In contrast, their number was reduced in thyrocytes of rats treated with
      100 mg Br/l (16, 66 and 133 days). Colloid droplets were only rarely found. There
      was no significant change in the amount of mitochondria, secondary lysosomes
      including phagolysosomes. Some thyrocytes showed signs of necrosis in animals
      following administration of 10 mg Br/l (16 days, 100 and 400 mg Br/l, 133 days).
      Clusters of thyrocytes with spongy cytoplasm and bizarre shaped nuclei were found
      in groups treated with 100 mg Br/l, and 400 mg Br-/l (133 days). These changes,
      with previously published light microscopical, radioanalytical and biochemical
      findings, confirm the goitrogenic effect of bromide.

PMID- 15255297
TI  - Cytochemical correlates of the sleep-wake interface: concerted expression of
      brain-derived nitric oxide synthase (bNOS) and the nicotinic acetylcholine
      receptor (nAChR) in a columnoid organization of the primate prefrontal cortex.
AB  - Nitric oxide (NO) was recently proposed to be involved in the sleep-wake cycle
      and cortical spreading depression. As a structural correlate of these functions,
      we found that bNOS IR was expressed by three cell types in the prefrontal cortex,
      viz. bipolar, multipolar, and stellate cells. Dendrites of bipolar cells
      established bundles resulting in a columnoid organization; in addition, the
      monoclonal antibody mAb 35 which labels subunits alpha1, alpha3 and alpha5 of
      nAChR, also visualized apical axons proceeding alongside the columnoids. In
      contrast, alpha-bungarotoxin which labels the alpha7-subunit of nAChR, visualized
      only perikarya of interneurons from where the apical axons arose. In the
      prefrontal cortex of monkeys which were anesthetized for 6-24 hours, only traces
      of the columnoid organization were found, while perikaryal bNOS and nAChR were
      invariably expressed. It is suggested that interactions between NO and
      presynaptically released ACh might be involved in cortical functions such as the
      sleep/wake cycle.

PMID- 15255298
TI  - Gender-dependent dimorphic teeth in four species of Mesoamerican plethodontid
      salamanders (Urodela, Amphibia).
AB  - The tooth shapes of premaxillary and maxillary teeth of adults of four
      Mesoamerican salamander species (Urodela, Plethodontidae) were examined. Using
      scanning electron microscopy we determined whether the monocuspid teeth that are
      present only on the premaxillary of sexually mature males belong to the conical,
      unbladed, monocuspid tooth type found in urodele larvae or whether they represent
      morphological variations of the typical, bladed, bicuspid teeth of metamorphosed
      individuals. The teeth of some studied species are, in fact, unbladed and in some
      cases show one very reduced tip. But none of the studied teeth is per
      definitionem monocuspid and no tooth shows an enameloid layer between dentine
      shaft and enamel cap, which is always present in the teeth of early urodele
      larvae. The "monocuspid" teeth of adult males of Mesoamerican plethodontid
      salamanders have to be considered a morphological variation of the metamorphosed,
      bicuspid tooth type typical for metamorphosed urodeles.

PMID- 15255299
TI  - Morphological evidence of collateral sprouting of intact afferent and motor axons
      of the rat ulnar nerve demonstrated by one type of tracer molecule.
AB  - In our experimental paradigm we sutured the distal stump of a transected
      musculocutaneous nerve to an intact ulnar nerve of the rat in an end-to-side
      fashion. We demonstrated the formation of collateral sprouts from intact afferent
      and motor axons by application of one type of molecule conjugated by two
      different fluorophores (Fluoro-Ruby and Fluoro-Emerald). Fluoro-Ruby and Fluoro
      Emerald were applied distal to end-to-side suture into fresh cut ends of the
      ulnar and musculocutaneous nerves, respectively. Formation of collateral sprouts
      was evidenced by findings of mixed (a yellow to orange color) fluorescence
      labeling of spinal motoneurons and dorsal root ganglia neurons. Colocalization of
      two different tracers retrogradely transported to the neurons was verified by the
      individual green and red fluorescence profiles analyzed by means of the computer
      assisted image-analyzing system. Our results unequivocally demonstrate that a
      nerve stump attached to an intact nerve can induce collateral sprouting of both
      afferent and motor axons.

PMID- 15255300
TI  - Morphology of the male reproductive duct system of Caiman crocodilus (Crocodylia,
      Alligatoridae).
AB  - The male reproductive duct system of Caiman crocodilus in different reproductive
      stages was studied using light and electron microscopy, to determine whether
      shared morphological features exist between Crocodylia and Aves, in concurrence
      with the Archosauria hypothesis. The sexual duct system of Caiman crocodilus is
      constituted of the rete testis, ductuli efferentes, ductuli epididymides, ductus
      epididymidis, and ductus deferens. The morphology and histochemical properties of
      these ducts suggest their involvement in seminal fluid production and/or its
      modification. Three types of non-ciliated cells were identified along the duct
      system. 1. The noncliated cells of the ductuli efferentes contain electron dense
      worm-like structures and coated vesicles, both related to absorptive processes,
      as has been suggested in Aves. 2. The non-ciliated cells of the ductuli
      epididymides have apical electron dense granules suggesting a secretory role, and
      3. The non-ciliated cells of the ductus epididymidis and ductus deferens did not
      exhibit conspicuous storage of secretory material, but have a prominent rough
      endoplasmic reticulum content indicating active protein production. The
      occurrence of abundant secretory granules in the epithelial cells of the distal
      ductus deferens during non-reproductive stages suggests its participation in the
      removal of luminal debris when the reproductive season ends. Additional ducts
      were observed running along the ductus deferens; they shared morphological
      characteristics with the ductuli epididymides. The maximum diameter and therefore
      the greatest sperm accumulation of the excurrent ducts were observed during the
      initial testicular regression. The comparative analysis suggests that the male
      reproductive system of the Crocodylia exhibits structural characteristics nearer
      to those of Aves than to Lepidosauria, Testudines, and Mammalia, additional data
      that support an Aves and Crocodylia sister group relationship.

PMID- 15255301
TI  - Androgen-dependent morphology of prostates and seminal vesicles in the
      Hershberger assay: evaluation of immunohistochemical and morphometric parameters.
AB  - The aim of this study was to evaluate androgen-like effects using
      immunohistochemical and morphometric methods. Therefore, orchiectomized Wistar
      rats (n > or = 13) were treated s.c. with 1 mg/kg bw/day testosterone propionate
      (TP) for 7 days and compared to orchiectomized rats without TP substitution (OX)
      and to an untreated intact control group. Sections obtained from prostates and
      seminal vesicles were stained with polyclonal and monoclonal antibodies against
      the androgen receptor (AR) and assessed densitometrically (intensity of the
      immunoreaction) and morphometrically (epithelial height, luminal area). TP caused
      an enhancement of staining intensity and an increase in organ weights, epithelial
      height and luminal area. The use of proliferation markers (PCNA, MIB-5) showed
      also a highly significant increase of immunoreactive cells in TP-substituted
      orchiectomized rats compared with the OX group. Based on the present data, the
      densitometric analysis of AR-immunoreactivity as well as the assessment of
      proliferation markers, epithelial height and luminal area proved to be sensitive
      parameters for the evaluation of androgen effects on prostates and seminal
      vesicles. In further studies these parameters will be used to test several
      industrial xenooestrogens as well as phytooestrogens on their possible androgenic
      capacity.

PMID- 15255302
TI  - A meta-analysis of superior thyroid artery variations in different human groups
      and their clinical implications.
AB  - We have investigated whether the presence, numerical variations and site of
      origin of the superior thyroid artery (STA) are influenced by the ethnic group
      and gender, whether the origin and caliber of this vessel are symmetrical, to
      what extent a non-selective thyroid angiography, either conventional or by
      digital subtraction, is effective in visualizing it, and whether this information
      may be useful in selected clinical conditions. A meta-analysis has been
      performed, including 24 library- and Medline-selected publications on Caucasoids
      (European and non-European) and East Asians and a set of original data on
      European Caucasoids. A total of 3453 Caucasoid and 931 East Asian items,
      including entire bodies, half bodies and arteries, were used. After testing the
      homogeneity of the available data sources in relation to the anatomical variables
      under study we calculated a cumulative value for each selected anatomical
      parameter and evaluated differences by non parametric statistics. Effectiveness
      of non-selective thyroid angiography was determined using sensitivity,
      specificity, positive and negative predictive values. A higher frequency of
      origin from the external carotid artery was present in Caucasoids than in East
      Asians. In contrast, a higher frequency of origin from common carotid artery was
      observed in East Asians versus Caucasoids. No gender differences were found for
      any of the parameters analyzed in East Asians. In addition, an equal probability
      of either asymmetrical or symmetrical origin on the two sides of the neck for STA
      was found in East Asians. In contrast, a symmetry of caliber for STA was found in
      European Caucasoids. Finally, only a moderate effectiveness of non-selective
      thyroid angiography, either conventional or by digital subtraction, was
      determined for visualization of STA in European Caucasoids. Statistically
      significant variations in some STA anatomical parameters occur between Caucasoids
      and East Asians. These differences, together with the high frequency of asymmetry
      for STA origin in East Asians and low effectiveness of STA visualization by non
      selective angiography in European Caucasoids, may result in useful information
      for clinical reasoning in selected conditions of the thyroid region.

PMID- 15255303
TI  - Morphometrical changes of the human uterine tubes according to aging and
      menstrual cycle.
AB  - Studies on the morphological changes in the human uterine tube according to aging
      and menstrual cycle so far have been limited to microscopic aspects such as
      cellular changes, mainly due to the inaccessibility of specimens. In this study,
      postmortem analysis using both macroscopic and microscopic methods was performed
      using 55 human uterine tubes. The numbers and the degrees of convolution, and the
      length of the uterine tube had a tendency to decrease according to the increase
      of age in women by fifties. Under the influence of menopause, the total areas of
      the tube, mucosal layer and lumen in the ampulla, and lumen in the isthmus and
      infundibulum were shown to decrease on cross section. However, in the isthmus and
      infundibulum, the cross sectional area of the tube and mucosal layer did not show
      statistically significant changes. In the women at reproductive stages, the cross
      sectional areas of the tube, mucosa and lumen showed variations among different
      individuals, which may be due to the influence of menstrual cycle rather than the
      increase of age. No venous engorgement of the tubes was observed at the early
      proliferative, the mid-secretory and the postmenopausal stage. By contrast, full
      engorgement was observed at the early secretory stage and the menstrual stage.

PMID- 15255304
TI  - Prenatal growth of the human tympanic membrane.
AB  - The questions connected with the morphology of developing tympanic membrane are
      rather inadequately dealt with in the relevant literature. The aim of this
      article has been the morphometric analysis of the prenatal growth of human
      tympanic membrane. The experiment was conducted on 33 fetuses aged from the 4th
      to 8th month of gestation. Significant individual variability of the tympanic
      membrane measurements was revealed in the material studied. The growth of the
      structure discussed was bilaterally symmetric during the whole period
      investigated. The fourth and 7th month of gestation seem to be the crucial stages
      for the tympanic membrane development. The measurements of the membrane exhibited
      the highest variability, simultaneously being negatively correlated with the
      fetal age in that periods. Relatively more intensive growth of the vertical
      diameter of the membrane was noted in the 5th and 8th months of gestation. In the
      8th month of gestation the tympanic membrane reached a vertically elongated
      shape, typical of the postnatal period. On the basis of our results it is
      possible to conclude that the quantitative developmental process takes place in
      the tympanic membrane till the end of the prenatal period, determining the final
      functional capacity of the structure discussed.

PMID- 15255306
TI  - [Rebellious, but much loved, needy students, requiring didactic quality and
      difficulty in preclinical education from the point of view of the medical
      students of Hamburg].
AB  - This paper reports the results of a retrospective evaluation of the quality of
      the preclinical undergraduate training by fifth year medical students at Hamburg
      Medical Faculty in 2001 by means of a standardized survey. The return rate was
      88% (N = 150). Students were rather critical about the quality of their
      preclinical training as a whole. They critisize a decrease in study motivation
      and express the feeling that the preclincal phase was not very useful for their
      actual clinical training. They demand a more clinically and patient oriented
      education, smaller groups and less "cramming". The evaluation results concerning
      the single disciplines were more favorable for the most important subjects.
      Especially anatomy, followed by physiology were best rated both with regard to
      learning benefit and to didactic quality. Most student opinions did not depend on
      sex, age or examination results. A positive correlation between learning benefit,
      didactic quality and degree of difficulty was found: contrary to prejudice
      difficult courses were rated higher with regard to learning benefit and
      educational quality.

PMID- 15255305
TI  - Low-dose radiation modifies the progression of chronic renal failure.
AB  - Previous studies have indicated that the application of low dose radiation to an
      arterial ligation has the potential to subsequently reduce or eliminate
      restenosis caused by smooth muscle cell proliferation. Sufficient kidney
      irradiation causes a radiation nephropathy and often leads to renal failure. In
      order to evaluate the effect of low-dose irradiation on the kidney we
      hypothesized that this particular therapy modifies renal injury in rats with
      renal ablation and subsequently slows the rate of the progression. For further
      clarification of the effect of irradiation at low doses, we determined
      proliferating cell nuclear antigen (PCNA) and monocyte chemoattractant protein-1
      (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats
      (n = 10) were studied during the two weeks after renal ablation. The left kidney
      was irradiated 24 hours after an operation in anaesthetised animals with 3 Grey
      in a single dose. Ablated rats without irradiation (n = 9) served as
      nephrectomized animals group. Rats without surgery and without radiation (n = 10)
      served as healthy controls. Renal damage was assessed using the following
      parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood
      pressure (SBP, mm Hg), serum creatinine (SCr, micromol/l). The indirect
      immunofluorescence method was used for the detection of PCNA and MCP-1
      expression. Glomerular and tubular immunostaining was scored semiquantitatively.
      Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus
      and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation
      application was associated with a significant reduction in PCNA and low MCP-1
      expression. This study shows that the application of low-dose irradiation has the
      potential to modify the progression of chronic renal failure in rats.

PMID- 15255307
TI  - [Carl Adolph von Basedow--150th anniversary of his death].
AB  - Carl Adolph von Basedow was the son of an aristocratic family and was born 1799
      in Dessau. He was the grandson of the famous pedagogue Johann Bernhard Basedow.
      He studied medicine at the university of Halle and spent two years in the
      surgical service of Paris hospitals--the Charite and the Hotel Dieu. In 1822, he
      settled in Merseburg as a physician. He was soon acclaimed as a genial and
      skilled helper in all branches of medical practice. He performed his own post
      mortem examinations and published findings on a number of different diseases. His
      famous contribution in the thyroid field appeared in 1840 entitled "Exophthalmos
      due to hypertrophy of the cellular tissue in the orbit". Exophthalmos, goiter and
      palpitation of the heart have become known as the Merseburg Triad. In 1848, he
      published the autopsy findings on a patient who died from "exophthalmic
      cachexia". In Germany and some other countries, the disease was named as Morbus
      Basedow since 1858. In 1854 he pricked in his finger in the postmortem room when
      examining a patient who had died of typhus and he succumbed to septicemia at the
      early age of fifty-five. The date of his death was April 11, 1854. On April 14,
      he was laid in the Sixtus Cemetery in Merseburg. Basedow postulated that a wrong
      mixing of the blood manifested in cell tissue congestion and glandular vegetation
      cause the manifestations of disease. If we abstract our modern knowledge and
      accept circulating antibodies and disturbance of the immune balance as a
      dyscrasia as well as the proliferation of lymphocytic clones and local cellulary
      infiltration in terms of immune thyroiditis and autoimmune orbitopathy as cell
      tissue congestion and glandular vegetations, then doubt arise whether we have
      indeed made much progress in the last 150 years. At least, respect for the genius
      of the general physician Carl Adolph von Basedow is becoming greater. We may all
      hope that in the contributions and the discussions, we shall learn where we stand
      at the end of the century and what new avenues of research are appearing on the
      horizon.

PMID- 15255308
TI  - [Genetic markers in thyroid autoimmune diseases].
AB  - Autoimmune disorders of the thyroid such as Graves' disease and Hashimoto's
      thyroiditis are the most common autoimmune diseases in the Western world. The
      frequent occurrence of both diseases in members of the same family indicates the
      influence of common genetic factors generally predisposing to thyroid
      autoimmunity. Common susceptibility loci have been mapped to the HLA region on
      chromosome 6p21 (HLA DR, HLA DQ), to chromosome 2q33 (CTLA4) and possibly to
      chromosome 8q24 (thyroglobulin). Additional susceptibility is conferred by
      genomic variants of the vitamin D system (vitamin D receptor and CYP1 alpha
      hydroxylase). Since these polymorphisms prevail also in healthy relatives they
      are necessary but not sufficient cofactors. The higher prevalence of thyroid
      autoimmune disease in women cannot be explained by susceptibility genes. The
      observation of microchimerisms in thyroid tissue might explain that an
      immunisation by fetal-maternal interaction can lead to thyroid autoimmunity in
      HLA risk combinations.

PMID- 15255309
TI  - [Thyroid hormone metabolism and action].
AB  - Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads
      to the activation or inactivation of the thyromimetic activity inherent to
      thyroid hormones. Alterations in the activities of the three selenocysteine
      containing enzymes, the iodothyronine deiodinases, have been reported during
      development and in specific cells and tissues of the adult organism. Furthermore,
      pathophysiological changes in the deiodinase expression lead to therapeutically
      relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of
      thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side
      chain or cleavage of their diphenylether bridge also contributes to both local
      and systemic supply of thyromimetic activity or hormone degradation. Further
      components mediating the pleiotropic action of thyroid hormones in part include
      redundant T3 receptors, binding and transport proteins, metabolising enzymes and
      T3-regulated gene products. This is achieved in a finely tuned manner with
      multiple feedback control, malfunction or complete failure of individual
      components and networks involved in the iodothyronine metabolism and thyroid
      hormone action can thus be compensated or prevented.

PMID- 15255310
TI  - [The practical relevance of the sodium iodide symporter].
AB  - The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein
      mediating the active transport of iodide in the thyroid gland and a number of
      extrathyroidal tissues, in particular in the lactating mammary gland. Because of
      its crucial role for the ability of thyroid follicular cells to trap iodide,
      cloning of NIS opened up an exciting and extensive new field of thyroid-related
      research. Cloning and molecular characterisation of NIS allows investigation of
      its expression and regulation in thyroidal and non-thyroidal tissues and its
      potential pathophysiological and therapeutic implications in benign and malignant
      thyroid disease. In addition to its key function in thyroid physiology, NIS
      mediated iodide accumulation allows both diagnostic thyroid scintigraphy and the
      effective therapeutic application of radioiodine in benign and malignant thyroid
      disease. Characterisation and application of NIS as a novel therapeutic gene for
      cytoreductive gene therapy of extra-thyroidal tumours and the presence of high
      endogenous NIS expression in the majority of breast cancers further suggest a
      promising role of NIS in the diagnosis and treatment of cancer outside the
      thyroid gland.

PMID- 15255311
TI  - [Thyroid hormones and the function of the vascular endothelium].
AB  - Numerous clinical studies point towards connections between cardiovascular
      morbidity and mortality and disorders of the thyroid function. This does not only
      apply to clinically manifest functional disorders, but also to their subclinical
      stages. The present review discusses in detail some of the most important
      endothelial changes, open questions and future developments.

PMID- 15255312
TI  - [Problems and new developments in the management of Graves' disease: medical
      therapy].
AB  - Since no causative treatment of Graves' disease is available, symptomatic therapy
      has been derived from clinical studies (evidence class I and II). To date,
      conservative treatment still has a relapse rate of 30-50% that is most likely due
      to the heterogeneity of patients. There is no clear data about the duration of
      therapy necessary for the individual patient. Previous prospective randomised
      studies have evaluated prognostic parameters including the use of levothyroxine
      for relapse prevention. For an improved characterisation of the natural course of
      Graves' disease, the period after drug withdrawal was studied. As patients
      treated with high doses of antithyroid drugs (< 10 mg thiamazole) and patients
      with large goitres (< 50 ml) often develop hyperthyroidism, they make likely
      candidates for radioiodine therapy or surgery. Smoking is a very strong
      independent risk factor for relapse. A prospective multi-centre trial of the
      Thyroid Chapter of the German Endocrine Society (DGE-SSD) demonstrated that the
      basal TSH is the strongest prognostic parameter to predict relapse of
      hyperthyroidism with an accuracy of 75%. In the present study, levothyroxine
      supplementation did not prevent recurrent hyperthyroidism. In order to avoid
      hypothyroidism levothyroxine should only be used in combination with antithyroid
      drugs. In the face of the amelioration of nutritional iodine uptake in Germany,
      the application of low doses of antithyroid drugs will very likely no longer be
      sufficient. Future therapeutic recommendations will be based on selection
      criteria such as iodine supplementation, volume of goitre, smoking habits and
      basal TSH. used in combination with antithyroid drugs. In the face of the
      amelioration of nutritional iodine uptake in Germany, the application of low
      doses of antithyroid drugs will very likely no longer be sufficient. Future
      therapeutic recommendations will be based on selection criteria such as iodine
      supplementation, volume of goitre, smoking habits and basal TSH.

PMID- 15255313
TI  - [Morbidity after subtotal and total thyroidectomy in patients with Graves'
      disease: the basis for decision-making regarding surgical indication and extent
      of resection].
AB  - Compared to radioiodine therapy the surgical treatment of Graves' disease aims to
      combine high therapeutic efficacy with low morbidity. According to the literature
      the risk for complications concerning recurrent laryngeal nerve paralysis and
      hypocalcaemia is lower after subtotal (0.6% and 0.9% respectively) than after
      total thyroidectomy (1.1% and 1.7% respectively). In contrast, the rate of
      persistent or recurrent thyrotoxicosis (3.2% and zero respectively) and the rate
      of worsening or newly developing endocrine ophthalmopathy is higher after
      subtotal resection than after total thyroidectomy (8% and 2% respectively). On
      the basis of these data, total thyroidectomy performed by an experienced surgeon
      is recommended in the case of complicated Graves' disease and in special
      situations (e.g. pregnancy and breastfeeding, suspected or proven concomitant
      thyroid malignancy, severe side effects of antithyroid drug treatment). Subtotal
      thyroidectomy should be reserved for patients with low activity of Graves'
      goitre, where radioiodine treatment has a similar effect but without the risks
      associated with surgery.

PMID- 15255314
TI  - [Radioiodine therapy for Graves' disease: problems and new developments].
AB  - In Germany, patients with Graves' disease are usually treated with radioiodine
      after unsuccessful antithyroid drug medication, occurrence of side effects from
      antithyroid drugs or an increased risk from surgery. In patients with normal or
      only slightly enlarged thyroid glands (volume < or = 50 ml), radioiodine therapy
      is particularly effective. Radioiodine is the preferential treatment for Graves'
      patients with high titres of TSH-receptor antibodies and cigarette smoking.
      Children are still rarely treated with radioiodine in Germany. In contrast,
      treatment with radioiodine should be more liberally applied in elderly patients
      with subclinical hyperthyroidism and cardiac symptoms. Individual dosimetry to
      determine the therapeutic activity is mandatory in Germany. Patients with large
      goitres obviously need higher organ doses than patients with smaller goitres or
      normal thyroid glands. Antithyroid drug treatment may interfere with radioiodine
      therapy. Therefore, it is recommendable to withdraw antithyroid drugs several
      days before treatment with radioiodine is initiated (and a preceding radioiodine
      uptake test is performed). In patients with Graves' orbitopathy prophylaxis with
      corticosteroids can prevent the worsening of symptoms that may be induced by
      radioiodine treatment. Currently, a risk adapted procedure is recommended
      according to which prophylactic medication with corticosteroids before applying
      radioiodine treatment is not necessary in patients with symptoms of orbitopathy
      and lack of other risk factors (cigarette smoking, in particular). Present
      results suggest that the risks of radioiodine treatment in Graves' disease
      patients are very low, while at the same time the cost-effectiveness of this
      treatment regimen is high.

PMID- 15255315
TI  - [Managing Graves' orbitopathy].
AB  - Inflammatory orbitopathy is the most common extrathyroidal manifestation of
      Graves' disease and is characterised by a lymphocyte infiltration into the
      peribulbar space. Interdisciplinary management is recommended for rapid diagnosis
      and effective therapy of patients with thyroid orbitopathy. Immunosuppressive
      treatment is often used initially, and by suppressing inflammatory changes, it
      may result in both subjective and objective improvement. On the long run, though,
      decompression surgery is actually regarded as the most effective treatment of
      thyroid eye disease.

PMID- 15255316
TI  - [Characteristic features of autoimmune thyroid disease in children].
AB  - The present review discusses in detail the most important problems of autoimmune
      thyroid disease in children and adolescents. There is a low incidence of
      autoimmune thyroid disorders in children and adolescents, the most important
      being Hashimoto's thyroiditis. Painless thyroid enlargement and delayed
      development are essential symptoms. Patients suffering from hypothyroidism or
      goitre should be treated with 1-thyroxin. The aim of treatment is to normalise
      metabolism and TSH levels. Graves' disease in children and adolescents is
      uncommon, and clinical features may be subtle. Typical eye symptoms are very
      often not present. Compared to older patients, the duration of symptoms is
      usually longer and the degree of hyperthyroidism more pronounced. This is why
      children require more time to achieve remission after anti-thyroid drug
      treatment. As already indicated, surgery is usually preferred to radioiodine.

PMID- 15255317
TI  - [Iodine and thyroid autoimmunity].
AB  - The pathogenetic mechanisms leading to the development of autoimmune disease of
      the thyroid are based on several different factors. The resultant immune response
      is related to both the genetic predisposition and other influencing factors such
      as iodine intake, a very important modulator of thyroid autoimmunity. To a large
      extent, the details of the mechanisms that induce the immune response and lead to
      chronic autoimmune thyroid reactions are still poorly understood. In genetically
      predisposed individuals the iodine intake modulates autoimmune thyroid reactions.
      Especially with acute or chronic increase of iodine intake it leads to a
      significant increase in the incidence and intensity of autoimmune thyroid
      disease. There is a need to further investigate whether the results of
      experimental animal studies can be generalised to humans. Epidemiological data
      from countries with sufficient or high nutritional iodine intake clearly show
      that in comparison to countries with iodine deficiency there is an increase in
      the incidence of autoimmune thyroid disease and a change in the pattern of
      manifestation, e.g. in the proportion of autoimmune thyroiditis and
      hyperthyroidism due to Graves' disease. At the same time, thyroid diseases
      related to iodine deficiency significantly decrease, which is to be expected with
      a continuously higher iodine intake.

PMID- 15255318
TI  - Induced abortion in Sri Lanka.

PMID- 15255319
TI  - Wound care in Sri Lanka: our patients deserve better care.

PMID- 15255320
TI  - Evaluation of a rapid whole blood immunochromatographic assay for the diagnosis
      of Plasmodium falciparum and Plasmodium vivax malaria.
AB  - OBJECTIVE: Microscopic examination of blood smears is the 'gold standard' for
      malaria diagnosis, but is labour intensive and requires skilled operators.
      Plasmodium vivax malaria accounts for up to 70% of infections in Sri Lanka. The
      objective of this study was to determine the effectiveness of an
      immunochromatographic test which can detect both the species of Plasmodium, P.
      vivax and P. falciparum, present in Sri Lanka. DESIGN: Prospective study from May
      2001 to March 2002. SETTING AND METHODS: All persons above 5 years of age who
      presented to the Malaria Research Station, Kataragama or the Anti-malaria Clinic,
      Kurunegala, with a history of fever were recruited to the study. Thick and thin
      blood smears were examined for malarial parasites. The rapid diagnostic test
      (RDT), ICT Malaria P.f/P.v (AMRAD ICT, Australia) was performed simultaneously by
      an independent investigator. The severity of clinical disease of all patients was
      evaluated. RESULTS: The study sample comprised 328 individuals of whom 126 (38%)
      were infected, 102 with P. vivax (31.1%) and 24 with P. falciparum (7.3%). The
      RDT was found to be highly sensitive (100%) and specific (100%) for the diagnosis
      of P. falciparum when compared with field microscopy. The sensitivity for the
      diagnosis of P. vivax malaria was only 70%. When P. vivax parasitaemia was
      greater than 5000 parasites/microL the RDT was 96.2% sensitive. A significant
      association was noted between the band intensity on the dipstick and both
      peripheral blood parasitaemia (p < 0.001) and clinical severity of disease with
      P. vivax (p = 0.011). CONCLUSIONS: The ICT Malaria P.f/P.v test can be used in
      Sri Lanka in the absence of microscopists.

PMID- 15255321
TI  - Met and unmet needs of children with epilepsy in a paediatric tertiary care
      setting.
AB  - OBJECTIVE: To investigate the extent to which the health needs were met or unmet
      in children with epilepsy attending a tertiary care outpatient setting. PATIENTS
      AND METHOD: A semi-structured interview was used to collect relevant information
      from the parents. It focused on ascertaining the quality of health care received
      by the children, including the extent to which attention was given to epilepsy
      related physical, behavioural, social and educational impairments that were
      identified by the parents. RESULTS: There was satisfactory seizure control in the
      majority. Most children received only one anticonvulsant and side-effects were
      reported to be minimal. A large majority had behavioural problems, and social and
      educational difficulties to a lesser extent. Parents were concerned about the
      implications of these problems, but there was little communication about them in
      the doctor-patient contact. Even where the problems were communicated, parent
      satisfaction about the interventions was low. Parents identified the availability
      of more consultation time and provision of more information on epilepsy as their
      expectations from doctors. CONCLUSIONS: This study shows that awareness and
      communication about the multiple health problems of children with epilepsy are
      necessary to improve the quality of health care given to them.

PMID- 15255322
TI  - Knowledge, behaviour and attitudes on induced abortion and family planning among
      Sri Lankan women seeking termination of pregnancy.
AB  - INTRODUCTION: In Sri Lanka over 500 induced abortions are done daily in spite of
      restrictive legislation. Experiences in other countries show that liberal laws
      alone have not solved the issues of induced abortions which may harm a woman's
      physical and mental health. OBJECTIVE: To determine the socio-demographic
      features of women seeking termination of pregnancy, and their knowledge, attitude
      and behaviour with respect to induced abortion and family planning. METHODS: A
      prospective study on a randomly selected group of 210 women attending a clinic in
      Colombo requesting termination of pregnancy. A pre-tested interviewer
      administered questionnaire was used for data collection. RESULTS: Over 80% of
      women seeking abortion were between 20 and 40 years of age. All religions were
      represented. 13% were single and 10% wanted to postpone a pregnancy. 38.6% had
      three or more children. In 90% the period of gestation was less than 10 weeks.
      Presence of a young child was the commonest reason for termination, followed by
      poverty. Only 0.9% were due to incest and foetal abnormality. 96% were not aware
      of adverse effects of abortion. 91% thought that induced abortion was immoral and
      94% did not know that it was illegal. 29% had previous terminations and post
      abortion contraception counselling was poor. Although 78% were knowledgeable on
      at least one method of contraception, only 16.3% were using it regularly.
      DISCUSSION: A majority used induced abortion as a family planning method.
      Improving accessibility and the quality of family planning services is of
      paramount importance. Every encounter of a woman with a health care worker should
      be an opportunity for counselling.

PMID- 15255323
TI  - Genetic testing for single gene disorders.
AB  - Genetic testing for single gene disorders is becoming available in Sri Lanka.
      While it offers many benefits, there are concerns about psychological and social
      problems that can be a consequence of such tests. This article aims to review the
      potential benefits and disadvantages of genetic testing, and recommends
      mechanisms that would help minimise problems associated with the inappropriate
      use of genetic tests.

PMID- 15255324
TI  - Do schools promote violence in Sri Lanka?

PMID- 15255325
TI  - Sugars, fruits and fructose drinks.

PMID- 15255326
TI  - Trichotillomania.

PMID- 15255327
TI  - Embryonal carcinoma presenting as unilateral leg swelling and weakness.

PMID- 15255328
TI  - Two families in Sri Lanka with Southeast Asian ovalocytosis.

PMID- 15255329
TI  - Meckel Gruber syndrome: occurrence in non-consanguineous marriages.
AB  - Meckel Gruber syndrome is an uncommon, lethal, autosomal recessive disorder,
      associated consistently with polycystic kidneys, posterior encephalocoele and
      polydactly. We report three cases in non-consanguineous marriages, suggesting
      that the single gene defect occurs more commonly in non-consanguineous marriages
      than mutant genes associated with other autosomal recessive disorders that are
      usually related with consanguineous marriages. The usefulness of prenatal
      diagnosis is discussed.

PMID- 15255330
TI  - Outcome of anastomotic urethroplasty in bulbomembranous urethral strictures.

PMID- 15255331
TI  - Factitious disorders, malingering or maladaptive coping strategies?

PMID- 15255332
TI  - Screening for diabetes mellitus in pregnancy.

PMID- 15255333
TI  - Neonatal jaundice due to maternal ingestion of "veniwelgata"?

PMID- 15255334
TI  - Cell bioscience.

PMID- 15255335
TI  - [Metrological analysis of calibration].

PMID- 15255336
TI  - [CRO 2004].

PMID- 15255337
TI  - Applicational possibilities of linear and non-linear (polynomial) regression and
      analysis of variance. III. Stability determination of pharmaceutical
      preparations: stability of diclofenac-sodium in Diclofen injections.
AB  - This paper presents the application of the regression analysis program and the
      program for comparing linear regressions (modified method for one-way, analysis
      of variance), writtens in BASIC program language, for instance, determination of
      content of Diclofenac-Sodium (active ingredient in DIKLOFEN injections, ampules a
      75 mg/3 ml). Stability testing of Diclofenac-Sodium was done by isothermic method
      of accelerated aging at 4 different temperatures (30 degrees, 40 degrees, 50
      degrees and 60 degrees C) as a function of time (4 different duration of
      treatment: (0-155, 0-145, 0-74 and 0-44 days). The decrease in stability
      (decrease in the mean value of the content of Diclofenac-Sodium (in %), at
      different temperatures as a function of time, is possible to describe by, linear
      dependance. According to the value for regression equation values, the times are
      assessed in which the content of Diclofenac-Sodium (in %) will decrease by 10%,
      of the initial value. The times are follows at 30 degrees C 761.02 days, at 40
      degrees C 397.26 days, at 50 degrees C 201.96 days and at 60 degrees C 58.85
      days. The estimated times (in days) in which the mean value for Diclofenac-Sodium
      content (in %) will by 10% of the initial values, as a junction of time, are most
      suitably described by 3rd order parabola. Based on the parameter values which
      describe the 3rd order parabola, the time was estimated in which Diclofenac
      Sodium content mean value (in %) will fall by 10% of the initial one at average
      ambient temperatures of 20 degrees C and 25 degrees C. The times are: 1409.47
      days (20 degrees C) and 1042.39 days (25 degrees C). Based on the value for
      Fischer's coefficien (F), the comparison of trenf of Diclofenac-Sodium content
      (in %) shows that, under the influence of different temperatures as a function of
      time, among them, depending on temperature value, there is: statistically very
      significant difference (P << .05) at 50 degrees C and lower toward 60 degrees C,
      i.e. statistically probably significant difference (P > 0.01) at 40 degrees C and
      lower towards 50 degrees C and there is no statistically significance difference
      (P >> 0.05) at 30 degrees C towards 40 degrees C.

PMID- 15255338
TI  - Influence of salt form and concentration on the absorption of magnesium in rat
      small intestine.
AB  - The influence of magnesium concentration and salt form on the absorption of this
      element in the rat small intestine was investigated. The following magnesium
      salts were studied: gluconate, fumarate, and chloride. At 1 and 5 mM
      concentrations absorption was most efficient from gluconate whereas at 10 mM
      absorption from fumrate was more efficient. Mg2+ absorption half-life (t50%)
      varied with salt and concentration. The Mg2+ absorption half-life for magnesium
      gluconate at 10 mM concentration was 42 times as long as at 1 mM concentration.
      The biggest area under the curve, which characterizes substance bioavailability,
      was observed for each of the investigated salts at 5 mM. Therefore, we may
      conclude that magnesium administration at 5 mM concentration would be optimal.

PMID- 15255339
TI  - Isolation and properties of glycosylated pig prolactin (G-PRL).
AB  - Isolation and properties of glycosylated pig prolactin (G-PRL)--Crude prolacting
      was received via extraction from lyophilized hypophyses with acidic 70% acetone,
      and then by protein precipitation via increasing acetone concentration in the
      extract to 92%. Received precipitate was dissolved in 0.1 M acetic acid and
      prolactin was precipitated in the isoelectric point at the pH = 4.97. Prolactin
      precipitate was dissolved in phosphate buffer pH = 7.50 and adsorbed on the DEAE
      Sephadex column, and then eluated with linear gradient at NaCl concentration
      range 0.00-0.40 M. Prolactin with molecular mass 24.0 kD was eluated at NaCl
      concentration 0.19-0.25 M. Using gel filtration method on Sephadex G-100
      glycosylated prolactin was divided into 2 fractions with molecular mass equal-
      55.8 and 17.4 kD. Both 24.0 kD--prolactin and its glycosylated form were
      characterized by high biological activity. Glycosylated prolactin contains among
      others mannose and fucose.

PMID- 15255340
TI  - Assessment of quality control parameters and interchangeability of multisourced
      metformin HCl tablets marketed in Nigeria.
AB  - A quality control assessment of five brands of metformin hydrochloride tablets
      marketed in Nigeria [Glucophage (R) (Merck, Quetta), Metformin BDC (Bangkok labs,
      Bangkok), Metformin (Medopharm, India), Glucophage (R) (Ilsan), Glucophage
      (Lipha)] was carried out in order to determine the brands that are
      interchangeable or switchable. The disintegration time, dissolution rate and
      absolute drug content were determined in simulated gastric fluid (SGF) and
      simulated intestinal fluid (SIF) without enzymes. The weight uniformity and
      hardness tests were also performed according to the official methods. A variation
      of the concept of dissolution efficiency (DE), known as predicted availability
      equivalent (PAE), was used to predict the likely in vivo bioavailability. Our
      results showed that all the five brands passed the uniformity of weight and
      disintegration tests. Dissolution efficiency was found to be higher in SGF than
      in SIF. In SGF, all the brands were bioequivalent. In SIF, all the brands, except
      Medopharm, were also bioequivalent. The study showed that four brands of
      metformin hydrochloride (Merck, BDC, Lipha and Ilsan) marketed in Nigeria are of
      acceptable standards and hence BDC, Lipha and Ilsan brands of glucophage are
      interchangeable with the innovator drug, glucophage R (Merck).

PMID- 15255342
TI  - Pharma bibliography: medicinal chemistry.

PMID- 15255341
TI  - Melt extrusion bioadhesive delivery of diclofenac sodium granules using theobroma
      oil.
AB  - Carbopol 941 (C-941), a bioadhesive polymer and theobroma oil (TEO) were used in
      the formulation of melt extrusion bioadhesive tablets (MEBT) of diclofenac (DC).
      Different batches of the MEBT were formulated using different combinations of C
      941 granules containing DC and TEO. The bioadhesive properties of the tablets
      were studied using a tensiometer by measuring the bioadhesive strength generated
      when the tablet interacts with the mucus of everted hog jejunum. Some physical
      properties of the tablets evaluated were weight uniformity, crushing strength,
      friability, tablet thickness and diameter liquefaction time and absolute drug
      content. Release of DC from the MEBT was carried out in simulated intestinal
      fluid (SIF), pH 7.2. The tablets had low liquefaction times and were highly
      bioadhesive. Result of the study indicated that TEO could be used in the
      formulation of MEBT of DC granulated with C-941 for prolonged and controlled
      delivery of DC.

PMID- 15255343
TI  - Pharma bibliography: technology.

PMID- 15255344
TI  - [Herbivore or carnivore? History of prions].
AB  - Transmissible subacute spongiform encephalopathies have been known for some times
      in man and in animals, but were considered of minor importance up to the
      development of the mad cow crisis. Bovine spongiform encephalopathy raises
      questions about nowadays farming and brings up the issue of cannibalism as a
      whole and imposed upon an herbivore. Even if the word cannibalism may seem
      excessive in the case of cattle, it is however true that BSE spreads from cow to
      cow through their feeding with meat and bone meal contaminated with infected
      bovine material. More generally this points out the problem of cannibalism among
      animal species.

PMID- 15255345
TI  - [Detection of transfusion transmitted virus (TTV) DNA in sera among three
      different population groups in Abidjan, Cote d'Ivoire in 2001].
AB  - The aim of this study was to determine the transfusion transmitted Virus (TTV)
      prevalence in three groups of population from Abidjan, Cote d'Ivoire. The A group
      contained 39 multitransfused patients, the B group contained 10 blood donors
      supposed to be healthy persons which have never been transfused and the group C
      contained 43 patients with chronic liver pathology. In this last group, 33
      patients had HBV positive serology and the 10 others, HCV positive serology. We
      used PCR to investigate TTV in patients serum. Detection rates were comprised
      between 67% and 82%. This is the first study to provide information about the
      high portage of TTV in ivorian population.

PMID- 15255346
TI  - [The spread of the wild Poliovirus in the rural environment, the case of the
      Adzope health district, Cote d'Ivoire].
AB  - Wild Poliovirus spreading in rural environment in Adzope, Cote d'Ivoire In order
      to determine the level of wild Poliovirus spreading among rural children in an
      endemic poliomyelitis country 469 stools samples, from children aged between
      three weeks and twelve years old were processed according to WHO procedures for
      transportation, conservation, isolation and identification of Poliovirus.
      Intratypic differenciation was performed by an antigenic method using monoclonal
      antibodies and a genomic RFLP (Restriction Fragment Length Polymorphism). 50
      Poliovirus strains (10.7%) were isolated and analyzed: 15 vaccine-like Poliovirus
      type 1 (30%), 30 vaccine-like Poliovirus type 2 (60%), 4 vaccine-like Poliovirus
      type 3 (8%) and one wild Poliovirus type 3 (2%). As expected, in the major cases
      the duration of post-vaccinal viral excretion did not exceed two months. However,
      in 14% of cases, it varied between 3 and 9 months after the third OPV dose. This
      long excretion could be due to an inefficient local intestinal immunity or no
      local immunity at all, in spite of the three OPV doses. These results argue in
      favor of an increase of the number of OPV doses in such endemic zones. Moreover,
      OPV strains are well-known to revert to pathogenicity in vaccinees, therefore,
      the long term excretion of pathogenic OPV derived strains by a certain amount of
      vaccinees needs to be considered quite seriously.

PMID- 15255347
TI  - [Characteristics of Enterococcus strains isolated from neutropenic patients at
      the National Bone-Marrow Transplantation Center of Tunis].
AB  - The frequency of digestive colonization of neutropenic patients by Enterococci
      during the phase of pre-transplant and post-transplant of bone marrow is
      important indeed as 441 Enterococcus spp strains have been isolated from stool
      cultures and other specimens whithin a period of 35 months in 80 patients. A
      quantitative stool culture was done on appropriate media. Simple bile-esculine
      agar (BE) and bile esculine-agar additionned with 6 mg/l of vancomycine (BEV)
      were used for detecting Enterococci. These organisms were taken into account,
      when then numeration was > 10(3) UFC/g of fecal sample on BE and in all cases on
      BEV. Species isolated were essentially Enterococcus faecalis (39.4%),
      Enterococcus faecium (34.4%) and Enterococcus casseliflavus (17%). These strains
      were characterized by a high frequency of high-level resistance to gentamicin
      (40.8%). Resistance to amoxicillin concerns 40% of E. faecium strains. Seventeen
      multiresistant strains of E. faecium isolated from 7 patients (colonized during a
      long period and receiving a gut decontamination treatment) were the subject of a
      phenotypic analysis (biotyping, antibiotyping and determination of MICs to beta
      lactam, aminoglycosides and glycopeptides). This analysis showed that these
      strains are distinguishable, endogenic and specific for each patient, the common
      multiresistance trait resulted from the selective pressure of decontamination
      treatment used for our patient.

PMID- 15255348
TI  - [Contribution of gene amplification in Mycobacterium ulcerans detection in
      exudates and cutaneous biopsies in Cote d'Ivoire].
AB  - Mycobacterium ulcerans skin ulceration is a major issue of public health in Cote
      d'Ivoire. The diagnosis of M. ulcerans infection is hampered by the slow growth
      of the bacterium in culture, implying a delay of several weeks before a specific
      diagnosis can be obtained. In Cote d'Ivoire the diagnosis of Buruli ulcer is
      almost based on clinical features. During the last decade, many studies have
      demonstrated the extremely high capacity of PCR for rapidly and specifically
      detecting bacteria and genes of interest. That ability has revealed PCR as a
      powerful tool in clinical microbiology studies. In this study we evaluated the M.
      ulcerans detection in specimens of exudates and biopsies collected from patients
      clinically suspected of Buruli ulcer and treated in "Raoul Follereau" centre of
      Manikro in the North-central region of Cote d'Ivoire. The microscopic research of
      BAAR in 185 swabs loaded with skin lesions collected from these patients showed a
      positive rate of 14.6%. The PCR detection in 48 h or 72 h of the M. ulcerans
      IS2404 and IS2606 in the swabs and in the 26 biopsies, from these patients,
      showed positive rates of 15.7% and 84.6% respectively and in the same samples.
      These results obtained with PCR detection of M. ulcerans insertions sequences
      suggest that this technique performed with exudates and biopsy can be used to
      confirm a routine specific diagnosis of M. ulcerans and early screening of Buruli
      ulcer in Cote d'Ivoire.

PMID- 15255349
TI  - [Neonatal septicaemia: bacteriological aspects and outcome in the university
      hospital center of Lome].
AB  - Despite the progress in neonatal intensive care and antibiotics, the neonatal
      septicaemia remains very frequent and lethal in tropical areas. OBJECTIVE: To
      study the bacteriology and outcome of the neonatal septicaemia through an
      analysis of 50 confirmed cases. METHODS: Every child aged of less than 29 days,
      suspected of infection and with at least one positive blood culture has been
      included. His perinatal antecedents, clinical features, bacteriological findings,
      treatments and clinical outcome have been collected. The patients have been
      divided into 3 groups in regard to the postnatal age at the first positive blood
      culture: before 48 hours, between 3 and 7 days and after 7 days of life. RESULTS:
      The neonatal septicaemia occurred in 50% of the cases before 48 hours, 24% from
      the 2nd to the 7th day and 26% from the 8th to the 28th day of life.
      Enterobacteriaceae (54%) with E. coli predominant (30%) and S. aureus (28%) were
      the most frequent germs and particularly during the first week of life: 20/27 and
      11/14 respectively. The resistance to the association of ampicillin or
      amoxicillin and gentamicin was 70% for Enterobacteriaceae and 71% for
      Staphylococci. The lethality was 36% with an excess of lethality for S. aureus
      (43%). CONCLUSION: The high rates of frequency and lethality of the neonatal
      septicaemia in tropical areas require a perinatal care improvement to reduce its
      morbidity and mortality.

PMID- 15255350
TI  - [Haemophilus influenzae, the second cause of bacterial meningitis in children in
      Madagascar].
AB  - The Haemophilus influenzae b is one of the main germs causing bacterial
      meningitis in children in countries where the vaccine anti-Haemophilus influenzae
      b is not widely used. In Madagascar, no epidemiological study on this germ has
      been carried out. The objective of this research is to assess the role of
      Haemophilus influenzae meningitis in Antananarivo and to determine its
      epidemiological aspects and evolution. A multicentric study coordinated by the
      Institut Pasteur de Madagascar included all children less than 15 years old with
      infectious syndromes associated to a syndrome of meningial irritation and/or
      convulsion and/or coma. These children were admitted in the pediatric service of
      the three main hospitals in Antananarivo from June 1998 and June 2000. A lumbar
      puncture was performed on each child; the cerebrospinal fluid was set aside for
      cytobacterial and biochemical controls completed with an antimicrobial
      sensitivity testing and a soluble antigens research. Out of 160 case studies, the
      Haemophilus influenzae b arrives at the second place among the agents causing
      bacterial meningitis in children. This type of bacteria is the source of 32% of
      meningitis after the Streptococcus pneumoniae (34%). It affects 96% of children
      less than two years old, with a maximal frequency before the age of one year. The
      lethality rate is 28.6% and the neurological sequelae were observed in 31.4% of
      patients. Haemophilus influenzae is sensitive to the third generation
      cephalosporins but shows high resistance to chloramphenicol (42%), amoxicillin
      (29%) and gentamicin (22%). The relatively high frequency as well as the high
      lethality rate caused by the Haemophilus influenzae b meningitis, affecting
      selectively the children under two years old, bring in the need to introduce the
      anti-Haemophilus influenzae b vaccine in the national vaccination program in
      Madagascar. This vaccine has proved to be efficient in many countries where it
      has been used. Furthermore, in the probabilistic treatment of bacterial
      meningitis in children, the third generation cephalosporins should be used in the
      first place.

PMID- 15255351
TI  - [Cysticercosis and epilepsy: a case-control study in Mbam Valley, Cameroon].
AB  - The impact of neurocysticercosis in Africa is not well known, and its role in the
      occurrence of epilepsy is not well defined. The concomitant high prevalence of
      both diseases in this region suggests a causal association of cysticercosis and
      epilepsy. The few attempts to find such a link in Africa have yielded discordant
      data. In order to answer this question, we conducted a case-control study between
      June and August 1998 in the Bilomo village in Central Cameroon, where a recent
      study had demonstrated very high epilepsy prevalence of 58/1000. Ninety-three
      epilepsy patients and eighty-one age matched controls were included. All subjects
      were examined by a neurologist and serology for cysticercosis was performed using
      an ELISA method. Serologies for cysticercosis were positive in twenty-nine out of
      one hundred and seventy four patients (16.7%; 95% CI: 11.6-23.2). Seventeen cases
      (18.3%) and twelve controls (14.8%) had a positive serology The odd ratio was 1.3
      (95% CI: 0.6-3.0). This study was not in favour of an epidemiological
      relationship between cysticercosis infection and epileptic disorders.

PMID- 15255352
TI  - [Non-Hodgkin's lymphoma in Dakar: study of 107 cases diagnosed between 1986 and
      1998].
AB  - Non-Hodgkin's Lymphomas (NHL) are the most prevalent malignant hemopathies in
      Senegal. In this study we have investigated the epidemiological aspects
      considering the HIV infection pandemic, and evaluated the diagnosis means and
      evolutive features of this disease in Dakar. Between 1986 and 1998 (13 years), we
      collected 107 cases of NHL, all histologically confirmed. Average age of patients
      was 31.4 years (2-85 years) and sex ratio was 21. HIV infection was found in
      three out of 62 patients tested (4.8%). At moment of diagnosis, 72% of patients
      were in stage III or IV according to the Ann Arbor Staging System. Large cell
      lymphomas were predominant (67.2%), followed by small lymphocyte lymphomas
      (24.2%) and follicular lymphoma with 8.4% of cases. Localization of lymphomas was
      exclusively nodal (30.8%) or extra nodal (31.7%) or mixed (37.3%). In
      therapeutical field, 21.5% of patients were treated with only symptomatical
      means. Chemotherapy was used in 54 patients (78.2% of treated patients), surgery
      was performed in 6 patients (8.6%), association of radiotherapy and chemotherapy
      in 5 patients (7.2%) and 4 patients (5.7%) were treated with surgery +
      chemotherapy. The average survival time was 344 days. Four patients (3.7%) were
      alive 3 years after diagnosis and only 2 patients (1.8%) after 5 years.

PMID- 15255353
TI  - [The first Congolese case of cervical clear cell adenocarcinoma].
AB  - The authors report the first Congolese case of uterine cervix clear cell
      adenocarcinoma in a menopausal multipara, whose mother had not been treated by
      diethystilboestrol (DES). The histological diagnosis was made on embedded
      paraffin samples, stained by HE and PAS. Discharged from hospital on parents'
      request in order to be on infusion and brew-based traditional treatment, the
      patient died at home two months after diagnosis.

PMID- 15255354
TI  - [Early diagnosis of leukaemia in the trisomic child. Congolese experience based
      on two cases].
AB  - We are reporting here two cases of acute leukemia in Congolese children with Down
      syndrome. They were aged 27 and 30 months. The two cases were revealed by anemia,
      hyperthermia with enlargement of the liver and the spleen. Clinical course was
      unfavorable. Therefore, the early diagnosis of leukemia remains very important in
      patient with Down syndrome presenting hyperthermia with hepatosplenomegaly.

PMID- 15255355
TI  - [Malignant solid tumours in Brazzaville children: epidemiological and anatomo
      pathological aspects].
AB  - In this retrospective study over six years the authors report 65 malignant solid
      tumours of the children under the age of 15 years old. The average age was 7.9
      years with a peak of frequency between 5 and 9 years. There was a male prevalence
      with a sex-ratio of 1.3. The most frequent histological types were: lymphoma of
      Burkitt (52%), retinoblastoma (20%), nephroblastoma (9%) and malignant tumours of
      the soft tissues (6%). The malignant solid tumours of the child are relatively
      rare and histologically very diversified.

PMID- 15255356
TI  - [Cryptococcal meningitis in HIV-infected patients at Bobo-Dioulasso hospital
      (Burkina Faso)].
AB  - Cryptococcus neoformans is an important fungal pathogen in immunocompromised
      patients. A retrospective study was conducted to investigate the occurrence of
      Cryptococcus neoformans infection in patients admitted to Bobo-Dioulasso Hospital
      over a 3 year-period. During this period, cryptococcal meningo-encephalitis was
      diagnosed in 36 individuals. The median age of the patients under study was 34.25
      years. There was a male preponderance (24 males/12 females) in our report.
      Typical presentations were persistent headaches (27 cases/36), neck stiffness
      (16/36), altered consciousness (14/36), fever (12/36) and convulsions (9/36).
      Oral candidiasis coexisted with cryptococcal meningitis in 7 patients. HIV
      serology was positive in all patients. At diagnosis, lymphocytes counts were <
      1500/mm3 in 66.66% patients. CSF examination with India ink helped to the
      diagnosis of cryptococcosis in all cases. Cryptococcus neoformans was associated
      with Streptococcus pneumoniae in 4 patients. 15/36 patients died within 1 to 29
      days after admission. High mortality was related to delayed diagnosis.
      Cryptococcal meningitis highly contributes to mortality in HIV-infected patients
      in Burkina Faso and it may occur in patients not severely immunocompromised
      patients. A need exists to improve strategies for clinical management of AIDS
      patients in poor African countries.

PMID- 15255357
TI  - [Psychiatric disorders in Madagascar: clinical study of 376 cases registered in
      Mahajanga].
AB  - Epidemiological and clinical data on psychiatric disorders from Madagascar are
      rare, particularly those issued from the coastal provinces. This retrospective
      study of cases, registered in the hospital of Mahajanga, from January 1st 1998 to
      December 31st 2000, gives a general scope on their frequency, their distribution
      and their features in this North Western littoral of the island. Concurrent
      resorts (traditional and religious healers) may reduce hospitalisation rate, by
      filtering minor and brief mental disorders at their level, but they delay the
      accurate management of severe or complicated cases, and enhance their frequency.
      The features of depression, the first cause of referrals (136/376), are
      characterized by the predominance of somatic complaints (89/136) over psychic
      symptoms (47/136), by that of persecutory ideas on self culpabilization and loss
      of self esteem, which accounts for the rarity of suicide (only 4/136 cases).
      Patients are sensitive to lower dose of antidepressant drugs, compared with
      patients from occidental countries. Psychosis, the second cause of medical resort
      (95/376), are essentially represented by schizophrenia (57/95), which involves
      males more than females (sex ratio 2), and displays more hebephrenic symptoms
      (31/57) than paranoid's (24/57). In spite of serious economical constraints,
      family dismissal is rare. Implementation of an accurate drug policy (long acting
      neuroleptics supply), along with this family support, may enhance patients'
      reintegration. Addictive (drugs, alcohol) and anxiety disorders seem to be
      underrepresented. In conclusion, the same pathologies reported in western
      literatures are encountered, but their features are sometimes modified by
      cultural particularities. A recent general population survey has brought
      complementary data, but this clinical study needs reproduction in other
      provinces, to be representative of the whole island.

PMID- 15255358
TI  - [Analysis of the diagnostic criteria used in childhood tuberculosis in a Cote
      d'Ivoire hospital].
AB  - Based on a retrospective study the authors analyzed the diagnostic criteria used
      in pediatric department in Yopougon CHU (teaching hospital), from January 1996 to
      December 2002. Fifty children, aged of 1 month to 15 years, have been studied.
      The tuberculosis contact was found in 18%. The diagnosis of tuberculosis was
      accurate in 32% and it was based on presumptive arguments in 68%. The pulmonary
      examination and pulmonary radiographs seem to be good criteria for the
      tuberculosis diagnosis. The pulmonary examination found an abnormality in 96%,
      and the radiographs found a pathological picture in 85% of cases. The skin test
      was positive in 42%. The Ziehl-Neelsen coloration was used to look for the acid
      fast bacilli and it was positive in 41%. But the two last examinations were not
      reliable in the case of HIV infection. The skin test which is very important for
      the diagnosis of tuberculosis is often negative among HIV infected children
      because of their anergy. On the other hand, the Ziehl-Neelsen coloration is based
      on the recognition of the acid-fast bacillus, which is not specific of the
      Mycobacterium tuberculosis. In our area the prevalence of HIV/AIDS is high, the
      atypical pneumonia with Mycobacterium were also frequent and may reveal a wrong
      positive diagnosis for the tuberculosis diagnosis, as they are also acid-fast
      bacillus.

PMID- 15255359
TI  - [Efficacy of chloroquine in treatment of non-complicated malaria with Plasmodium
      falciparum in children at the San Pedro dispensary in Cote d'Ivoire].
AB  - A survey has been carried out in south-west of Cote d'Ivoire in order to study
      chloroquine resistance in treatment of malaria according to 14 days protocol of
      WHO (World Health Organisation) (1996) for evaluation of antimalarial drugs
      activity; 63 children, aged from 6 months to 15 years and suffering from
      noncomplicated malaria due to Plasmodium falciparum, received by oral way 25
      mg/kg of chloroquine over three days (10-10-5). During the survey, they were
      subjected to a clinic and parasitologic (thick and thin blood film) follow up. We
      obtained, for 51 children (81%), a satisfactory clinical answer, for 8 children
      (13%) an early therapeutic failure and for the other 4 (6%) a late therapeutic
      failure. Moreover, we obtained 40% of failure in children of less than 24 months
      old, 25% between 24 months and 59 months and 7% beyond 6 years old.

PMID- 15255360
TI  - [Comparative study of neonatal bacterial meningitis in Lome, Bobo-Dioulasso,
      Casablanca and Lyon].
AB  - Bacterial meningitis in new-borns remains a serious event because of its high
      mortality and morbidity rates in Africa. OBJECTIVE: To identify the clinical and
      bacteriological epidemiology and the outcome of neonatal bacterial meningitis in
      three African cities. METHOD: We have analysed and compared three hospital
      studies done in humid tropical, Sahelian, and desert Africa with a European
      study. RESULTS: Compared with the European study this African study is
      characterized by a high mean frequency of neonatal meningitis (6 cases per year
      against 1.4), more important risk factors linked to pregnancy and childbirth (50%
      against 33%), high rates of death (61 to 68% against 5%) and sequelae (25 to 40%
      against 30%), rarity of Streptococcus agalactiae (7 to 15% against 38%) and
      absence of Listeria. Enterobacteriaceae were predominant both in African (50 to
      68%) and European (43%) studies. E. coli appeared as the most frequent germ in
      both European and African studies and Salmonella as more frequent in Sub-Saharan
      Africa than in occidental countries. CONCLUSION: The epidemiological,
      bacteriological and evolutional aspects of the neonatal meningitis were identical
      in the three African cities. The African studies were different from the European
      only by their high incidence, the rarity of S. agalactiae and Listeria and the
      difficulties of bacterial diagnosis and management, all might explain the high
      rates of death and sequelae. An epidemiological survey and adequate antimicrobial
      therapy according to antibiotic susceptibility may improve the outcome.

PMID- 15255361
TI  - [Cervix cancer screening in a health district (Burkina Faso) by voluntary
      biopsies after the application of acetic acid and lugol].
AB  - A voluntary screening of uterus cervix cancer took place in Kossodo health
      district from February 1st 2001 to April 30th 2002. It involved the age-group
      women of 25 to 59 years. This study included 239 women given a participation rate
      of 6.8%. We had sampled young women in three categories with average age of 38
      years: a) doing a remunerated job (64.9%); b) mostly educated (85.3%); and c)
      married (86.2%). The visual inspection was the method used after the application
      of 4% acetic acid followed by that of lugol. In all 74 biopsies have been
      undertaken. Furthermore, we have noticed a 4.2% prevalence of pre-cancerous
      injuries. The cancerous lesions represented 2.5% of the sampling and the
      inflammatory lesions 13.4%. VPH infection was found on 2.5% samples and
      condylomatous injuries in 5% cases. This experience would deserve to be carried
      out always and a cervix cancer screening campaign held at national level.

PMID- 15255363
TI  - Adjustable and non-adjustable strabismus surgery: a retrospective case-matched
      study.
AB  - Adjustable suture strabismus surgery was introduced to improve results in
      unpredictable strabismus cases. However, its usage is increasing and in some
      centres is routine. The present authors propose that the routine use of the
      adjustable suture technique can only be justified if it can be shown to confer an
      advantage to the patient. In a retrospective analysis of matched data, they
      compared the results of their adjustable with non-adjustable strabismus surgery.
      The adjustable suture procedures performed during a 5-year period, on non-thyroid
      eye disease patients, were matched to non-adjustable cases according to the type
      and aetiology of strabismus and the magnitude of deviation. Pairs were matched as
      closely as possible according to age and strabismus surgery history. All cases
      were incomitant. The surgical results of the two groups were analysed with regard
      to the pre-operative and post-operative angles of deviation, the post-operative
      drift, and a successful outcome, pre-defined by carefully selected criteria.
      Twenty-six cases were analysed in each of the two groups. Mean pre- and post
      operative angles of deviation showed no significant difference between the two
      groups. 'Success' rates were 81% in the adjustable group and 88% in the non
      adjustable group. Given that the success rate of the two techniques is similarly
      high, a much larger study is required to detect a difference in results, with
      statistical significance. The authors conclude that there is currently
      insufficient evidence that patients, without thyroid eye disease, benefit from
      the longer and potentially uncomfortable procedure of adjustable suture
      strabismus surgery to support its rapidly growing use and that a prospective
      randomised controlled trial is indicated.

PMID- 15255362
TI  - [Four year management of HIV serology at the National Center of Blood Transfusion
      in Conakry].
AB  - From January 1997 to December 2000, 21145 blood donations have been collected and
      tested for anti-HIV antibodies by the National Center of Blood Transfusion of
      Conakry (NCBT). 347 were positive, confirmed by Western Blot (312 HIV-1, 20 HIV-2
      and 15 HIV1-2). HIV seroprevalence in tested blood donations showed a slow
      decrease by year: 1.87% in 1997 to 1.79% in 2000. The distribution according to
      donation type was 1% for volunteer donors and 2% for family donors.
      Seropositivity HIV rates according to sex indicate that the female donors are
      more infected than male donors. Among 347 seropositive, 83% were more than 20
      years old. The seroprevalence is higher in soldier blood donors 3.72% (53/1422)
      than in student donors 0.55% (43/7712). The number of seropositive results found
      during these 4 years is not really representative of the HIV spreading infection
      in Guinean population, but their distribution according to sex and age is very
      close to the distribution of the AIDS cases in Guinea.

PMID- 15255364
TI  - Benign recurrent abducens (6th) nerve palsy in two children.
AB  - Benign recurrent abducens (6th) nerve palsy is rare. We found 23 cases in
      children reported in the literature; however, many of these cases followed
      immunization or were associated with viral illness. Here we report two cases of
      recurrent abducens nerve palsy with no obvious etiology. The diagnosis should be
      considered in any child who experiences abducens nerve palsy in the absence of
      any underlying pathology or precipitating factors.

PMID- 15255365
TI  - Scleral perforations in strabismus surgery: incidence and role of prophylactic
      cryotherapy--a clinical and experimental study.
AB  - PURPOSE: To determine the incidence of scleral perforations in strabismus surgery
      in a tertiary centre setting in India and to evaluate the risk or benefit, if
      any, of prophylactic cryotherapy following experimental scleral perforations in
      rabbits. METHODS: Seven hundred eyes of patients that had undergone strabismus
      surgery (1121 procedures) were examined postoperatively by indirect
      ophthalmoscopy. In the experimental component, 20 rabbit eyes were perforated
      with a 6-0 polyglactin suture. In each rabbit, one eye acted as a control while
      the other eye received a 20 seconds application of prophylactic cryo at the
      perforation site. They were then monitored for 6 weeks before subjecting some to
      histopathological examination by light and electron microscopy. RESULTS: Ten
      scleral perforations were detected in 9 of the patients (incidence of 1.42% of
      the eyes and 0.89% of the strabismus procedures). In the rabbits, a chorioretinal
      scar was seen in all perforated eyes. A mild cryo reaction was observed in the
      cryoed eyes. No other sequelae were seen. Histopathologic studies showed changes
      consistent with the normal healing process. CONCLUSIONS: Of the human eyes
      screened, 1.42% showed evidence of scleral perforation following strabismus
      surgery. In no case were sequelae leading to visual loss observed. In the rabbits
      no sequelae were observed at 6 weeks of follow-up apart from a chorioretinal scar
      and a cryoreaction in those eyes in which cryoprophylaxis had been given. Mild
      cryoprophylaxis did not exert any positive or negative influence on the natural
      course of scleral perforation in our short-term animal study.

PMID- 15255366
TI  - One-stage vs. two-stage adjustable sutures for the correction of esotropia.
AB  - BACKGROUND: The aim of this study was to evaluate the stability and the level of
      postoperative consciousness, nausea and vomiting, ocular pain, starting oral
      intake and activity, and cost-effectiveness in patients undergoing medial rectus
      recession surgery using an adjustable suture technique that was performed by two
      different methods. METHOD: In this prospective study, we evaluated 78 patients
      undergoing medial rectus recession surgery. Thirty-eight patients were operated
      by a one-stage technique in which the whole operation was done under topical
      anesthesia and adjustment was done on the operating table, while 40 patients were
      operated by a two-stage technique in which the operation was done under general
      anesthesia and adjustment was done the following day at the patient's bedside.
      The results were recorded and compared according to the parameters given above. A
      scoring system was used to assess all these parameters except for stability. The
      stability of the procedures was evaluated according to the degrees of squint
      immediately after the adjustment and at least three months thereafter. RESULTS:
      There was no significant difference between the procedures with regard to
      stability and ocular pain. During the early postoperative period, the level of
      consciousness was better and nausea and vomiting occurred less frequently in the
      patients operated by the one-stage procedure. Postoperative activity and oral
      intake returned to normal status more quickly in the one-stage group and the one
      stage procedure was cost-effective. CONCLUSION: We conclude that although both
      procedures provide satisfactory and stable results, the one-stage procedure has
      significant advantages over the two-stage procedure for medial rectus recession
      surgery in suitable cases.

PMID- 15255367
TI  - Effectiveness of retroequatorial recession surgery in congenital nystagmus.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the effectiveness
      of the retroequatorial recession technique in the surgical treatment of nystagmus
      and associated strabismus. METHOD: The effect of large recessions of four
      horizontal extraocular muscles was analyzed qualitatively in seven patients with
      congenital nystagmus. RESULTS: The ages of the patients ranged between 12 and 42
      years (mean, 21.5 years). Of the seven patients, four had motor and three had
      sensory nystagmus. Visual acuity increased in five (71.4%) patients. Planned
      recovery of associated strabismus was attained in six patients (85.7%). In five
      patients who had abnormal head position, the head positions and nystagmus
      intensities were found to be decreased. No postoperative complication, such as
      diplopia, was encountered. CONCLUSION: The retroequatorial recession technique is
      preferable in patients who have congenital nystagmus, especially in the presence
      of horizontal squint associated with low visual acuity, because of its success in
      increasing visual acuity and decreasing the amplitude of nystagmus, its
      reversibility, making posssible new operations in the future, as well as the
      absence of any significant complications.

PMID- 15255368
TI  - Diagnostic occlusion test in cases of unilateral strabismus sursoadductorius.
AB  - PURPOSE: To investigate the diagnostic occlusion test (OT) according to Marlow in
      strabismus sursoadductorius (StS; also known as 'unilateral superior oblique
      palsy') and its implications for surgical treatment. METHODS: In 67 cases of StS,
      angles of strabismus were measured before and after patching the affected eye for
      three days. Horizontal, vertical and torsional deviations were measured in front
      of the tangent screen of Harms in nine directions of gaze. RESULTS: After OT,
      most cases of StS showed the following distribution of vertical deviation (VD) on
      horizontal versions: setting the VD in 30 degrees adduction to 100%, VD in
      primary position (PP) was 50%, VD in abduction 14%, excyclotropia in PP about 40%
      of the amount of VD. Those StS-cases showing the same distribution of VD on
      horizontal versions before and after OT were called 'typical' ones (27% of the
      patients). However, 73% of the patients showed a different distribution before
      OT: 68% VD in PP, 36% VD in abduction, excyclotropia of 20% in PP. After OT these
      cases converted to the normal pattern described above: VD in PP was 53 % and VD
      in 30 degrees abduction was 19%, excyclotropia in PP was 36%. CONCLUSION: In
      'typical' StS-cases, OT is not necessary. 'Atypical' cases, however, can be
      converted into 'typical' ones: they get more incomitant VD on horizontal versions
      and greater excyclotropia in PP. As VD in adduction remains almost the same in
      both groups after OT, surgery can be based on the angle in adduction. In
      individual 'atypical' patients the amount of oblique muscle surgery has to be
      modified after OT.

PMID- 15255369
TI  - Christian Theodor Georg Ruete: the first strabismologist, coauthor of listing's
      law, maker of the first ophthalmotrope and inventor of indirect fundoscopy.

PMID- 15255370
TI  - Local regulatory factors in regulation of ovarian function: role of prorenin
      renin-angiotensin-system.
AB  - During reproductive life in the female, there is a continuous flow of growth,
      maturation and demise of ovarian follicles, unless pregnancy occurs. Although
      ovarian function is primarily controlled by the hypothalamus-pituitary-axis,
      there is no doubt that a hormonal microenvironment specific for each individual
      follicle is established, that finally determines whether a follicle ovulates and
      becomes a corpus luteum or undergoes atresia. In this respect, autocrine and
      paracrine factors that act alone or modulate gonadotropins action are of
      paramount importance. In this article, we want to introduce the ovarian prorenin
      renin-angiotensin-system (PRAS) and summarize what is actually known about its
      involvement in ovarian physiology and pathology.

PMID- 15255371
TI  - Zona pellucida glycoproteins based immunocontraceptive vaccines: strategies for
      development and their applications.
AB  - The mammalian oocyte is surrounded by an extra-cellular matrix, the zona
      pellucida (ZP), composed of three major glycoproteins (ZP1, ZP2 and ZP3). The ZP
      glycoproteins, by virtue of their tissue specificity and critical role during
      mammalian fertilization, have emerged as potential candidate antigens for the
      development of an immunocontraceptive vaccine. Molecular characterization of ZP
      glycoproteins from several species, reveals a variable degree of homology among
      the deduced primary amino acid sequences, which provided an opportunity to
      undertake active immunization studies in heterologous animal models. Active
      immunization of various animal species with either native ZP glycoproteins or
      those obtained by recombinant DNA technology led to the inhibition of fertility.
      Thus ZP glycoproteins based immunocontraceptive vaccines offer an attractive
      proposition for controlling wild life population. To make it a practical
      proposition, additional research inputs are required to optimize and devise novel
      strategies for vaccine delivery. Observed ovarian dysfunction, often associated
      with immunization by ZP glycoproteins is one of the major stumbling blocks for
      their use in humans. Ongoing studies to delineate appropriate B cell epitopes of
      ZP glycoproteins that are devoid of oophoritogenic T-cell epitopes, which will
      inhibit fertility without concomitant oophoritis, will be critical to determine
      their feasibility for human use.

PMID- 15255372
TI  - Endocrine characteristics of polycystic ovary syndrome (PCOS).
AB  - Polycystic ovary syndrome (PCOS) is probably the most prevalent endocrinopathy in
      women and the most common cause of anovulatory infertility. Patients with PCOS
      have clinical and biochemical features consistent with the ultrasound diagnosis
      and they are likely to face the problems of hyperandrogenism, subfertility and
      recurrent miscarriage. The aim of the present review is to summarize our present
      knowledge on the hormonal background of this very prevalent syndrome and to give
      some clinical examples how the present knowledge can be applied to treat PCOS
      patients according to their current problem, such as menstrual cycle disorder,
      hirsutism, infertility or to prevent late consequences as diabetes mellitus. The
      etiology and pathogenesis of PCOS is still a matter of controversies, but it is
      apparent that inappropriate gonadotropin secretion, obesity, hyperinsulinism and
      insulin resistance are the major determining factors in the development of
      ovarian hyperandrogenism an chronic anovulation. Reversal of insulin resistance
      in PCOS constitutes the fundamental goal in the management of hyperandrogenic
      anovulatory infertility and in the prevention of long-term consequences. The
      value of the insulin sensitizer metformin therapy awaits further evaluation and
      it should be integrated in the spectrum of therapeutical options that include the
      discussed surgical methods and GnRH analogues as well.

PMID- 15255373
TI  - Congenital adrenal hyperplasia: biochemical and molecular perspectives.
AB  - Congenital adrenal hyperplasia is a disorder occurring in both sexes and is the
      commonest cause of ambiguous genitalia. It is a group of autosomal recessive
      disorders in which, on the basis of an enzyme defect the bulk of steroid hormone
      production by adrenal cortex shifts from corticosteroids to androgens. Autosomal
      recessive mutations in the CYP21, CYP17, CYP11B1 and 3betaHSD genes that encode
      steroidogenic enzymes, in addition to mutations in the gene encoding the
      intracellular cholesterol transport protein steroidogenic acute regulatory
      protein StAR can cause CAH. Each of the defects causes different biochemical
      consequences and clinical features. Deficiencies in 21 hydroxylase (21-OH) and
      11beta-Hydroxylase (11beta-OH) are the two most frequent causes of CAH. All the
      biochemical defects impair cortisol secretion, resulting into compensatory
      hypersecretion of ACTH and consequent hyperplasia of the adrenal cortex. Research
      in recent years has clarified clinical, biochemical and genetic problems in
      diagnosis and treatment of the disorders. Expanding knowledge of the gene
      mutations associated with each of these disorders is providing valuable
      diagnostic tools in addition to the biochemical profile and phenotype. Genotyping
      is useful in selecting instances to provide genetic counseling and to clarify
      ambiguous cases.

PMID- 15255374
TI  - Conservation of wild animals by assisted reproduction and molecular marker
      technology.
AB  - Wild animals are an integral component of the ecosystem. Their decimation due to
      abrupt natural calamities or due to gradual human intervention would be
      disastrous to the ecosystem and would alter the balance in nature between various
      biotic components. Such an imbalance could have an adverse effect on the
      ecosystem. Therefore, there is an urgent need to put an end to the ever
      increasing list of endangered species by undertaking both in situ and ex situ
      conservation using tools of modern biology, to ascertain the degree of genetic
      variation and reproductive competence in these animals. This review highlights
      the development and use of molecular markers such as microsatellites,
      minisatellites, mitochondrial control region, cytochrome b and MHC loci to assess
      the genetic variation in various Indian wild animals such as the lion, tiger,
      leopard and deer. The review also presents data on the semen profile of the big
      cats of India. Reproductive technologies such as cryopreservation of semen and
      artificial insemination in big cats are also highlighted.

PMID- 15255375
TI  - Stem cell research: its relevance to reproductive biology.
AB  - Stem cells provide an excellent model system to understand the differentiation,
      development and functioning of gonads, and further use of these cells in
      transplantation or cell-based therapies. Embryonic germ cells present as a better
      source of pluripotent stem cells. The germ cells are specialized cells, which
      differentiate into sperm or oocytes. Spermatogonial stem cells are the only stem
      cells in the adult mammalian body that can be recognized and studied at cellular
      level with respect to proliferation and differentiation. In the present study,
      basic process of spermatogenesis, testicular niche and molecular regulation of
      spermatogenesis and density regulation has been discussed. Research on oogonial
      stem cells has recently been encouraged due to the demand for oocytes for various
      research purposes. Mechanism of regulation of follicle formation, oocyte
      attrition and follicle development and atresia are only partially understood.
      Hence, the stages of development, its interaction with the neighbouring somatic
      cells during each developmental stage and the molecular regulation underlying it
      has been reviewed. These studies will result in establishment of treatment of
      ovarian disorders, and in identifying cure for infertility that occurs due to
      ovarian pathophysiology. Indian scenario in terms of stem cell research and its
      benefits is also discussed.

PMID- 15255376
TI  - Functional roles of plasma membrane localized estrogen receptors.
AB  - A series of emerging data supports the existence and importance of plasma
      membrane localized estrogen receptors in a variety of cells that are targets for
      the steroid hormone action. When estradiol (E2) binds to the cell surface
      protein, the ensuing signal transduction event triggers downstream signaling
      cascades that contribute to important biological functions. Aside from the
      classical signaling through nuclear estrogen receptors, we have provided evidence
      for the functional roles of an estrogen receptor localized in the plasma
      membrane. This review highlights some of the recent advances made in the
      understanding of the genomic/non-genomic actions of plasma membrane localized
      estrogen receptors.

PMID- 15255377
TI  - Expression and regulation of integrin receptors in human trophoblast cells: role
      of estradiol and cytokines.
AB  - Embryo implantation and placentation are dynamic cellular events that require not
      only synchrony between the maternal environment and the embryo, but also complex
      cell-cell communication amongst the implanting blastocyst and the receptive
      endometrium through integrins, a large family of proteins involved in the
      attachment, migration, invasion and control of cellular functions. Integrins
      display dynamic temporal and spatial patterns of expression by the trophoblast
      cells during early pregnancy in humans. However, the precise mechanism of embryo
      implantation and the modulation of the integrin receptors during blastocyst
      attachment and further implantation remain elusive in the humans. The present
      study elucidates the expression and hormonal modulation of fibronectin,
      vitronectin and laminin integrin receptors by estradiol and IL-1alpha in human
      trophoblast cells. Human first trimester trophoblast cells showed the induction
      of the classical estrogen receptor (ER)-alpha by its own ligand, estradiol.
      Treatment with either estradiol or IL-1alpha induced the expressions of alpha4,
      alpha5, alpha6 and alpha(v) integrin receptor subunits at both the mRNA and
      protein levels, while expression of beta1 remained unaltered. Furthermore,
      estradiol upregulated the expression of IL-1alpha, thereby suggesting the
      possibility that estrogen may either directly or via the proinflammatory cytokine
      induces the expression of the cell surface integrin receptors. The findings
      delineate the role of hormones and the cytokines in modulating the adhesiveness
      and attachment of the trophoblast cells. This may reflect the in vivo scenario
      where the implanting embryo is surrounded by a hormone-cytokine rich uterine
      microenvironment that may precisely regulate the expression of integrins and
      thereby facilitate implantation.

PMID- 15255378
TI  - Embryo-endometrial proteases during early mammalian development.
AB  - In mammals, extensive remodeling of uterine endometrial matrix occurs during
      reproductive cycle and blastocyst implantation. This is regulated by a variety of
      molecules such as hormones, growth factors, cytokines and proteases. In this
      article, we review the current state of knowledge available on various proteases
      and their inhibitors functionally involved in the embryo-endometrial tissues and
      present some data on endometrial proteases in hamsters and rats during estrous
      cycle and early pregnancy. We demonstrate the presence of at least four
      gelatinolytic activities in endometrial samples, belonging to gelatinase-A and -B
      categories and their dependence on calcium/zinc ions for enzyme activity and,
      their interrelationships between zymogen and active forms. We believe that the
      embryo-endometrial proteases are essential for hatching of blastocysts and for
      the dynamic remodeling of endometrial tissues, occurring during the critical peri
      implantation period.

PMID- 15255379
TI  - Epididymis as a target for contraception.
AB  - Advantage of using a vaccine based on sperm antigens is that it can be used both
      in males and females as individuals who have antisperm antibodies are usually
      infertile but otherwise healthy. Several sperm specific antigens identified as
      prospective candidates for immunocontraception are of testicular origin. For the
      purpose of immunocontraception it may be desirable not to disrupt spermatogenesis
      and testicular function. Concept of post testicular maturation of spermatozoa has
      been very well established. During post testicular voyage spermatozoa undergo a
      series of complex and sequential events which transforms the immature immotile
      spermatozoa into mature sperm. Acquisition of functional maturity is necessary
      for progressive motility, zona pellucida recognition culminating in sperm egg
      binding. Importance of epididymal maturation is highlighted by the fact that high
      percentage of male infertility in human originates from the malfunction of the
      epididymis. The epididymis has also shown to be involved in sperm storage and
      provides an adequate environment for final maturation of the sperm. It provides a
      conducive microenvironment by virtue of which the spermatozoa are protected
      during the storage. In view of this it is imperative that more attention needs to
      be focused on epididymal antigens. The information obtained will enable us to
      identify epididymal antigens relevant to fertility and also help in infertility
      diagnosis.

PMID- 15255380
TI  - Progesterone receptors on human spermatozoa.
AB  - Progesterone, primarily recognized as a female steroid hormone, is reported to
      affect several sperm functions especially capacitation, motility and acrosome
      reaction. These effects of progesterone on the spermatozoa are mediated via the
      progesterone binding sites/progesterone receptor (PR) on the acrosomal membrane.
      These receptors in response to progesterone increase the intercellular Ca2+
      levels and stimulate Ca2+ influx in the mature human spermatozoa via non-genomic
      mode of actions. Characterization of this receptor reveals that the sperm PR is
      masked protein and is exposed to the surface by some non-ionic detergents.
      Localized on to the acrosome region of the spermatozoa, these receptors are
      recognized by most antibodies directed towards the C-terminal region of the
      conventional PR. The estimated molecular weight of PR on spermatozoa varies from
      27 kDa to 85 kDa. At the molecular level, sequences encoding for the entire DNA
      and hormone binding domains of the conventional PR are detected in the mRNA
      derived from spermatozoa. No insertions, deletions or mutations are detected in
      this region. These results are suggestive of the fact that at least the C
      terminal region of the conventional PR is conserved in the sperm. It is
      hypothesized that post-translational modifications or peptide splicing of the
      conventional PR in spermatozoa may possibly lead to the variant of the steroid
      hormone receptor. Detailed characterization of the sperm PR will be important in
      understanding the alternate non-genomic mode of action of steroid hormone
      receptors.

PMID- 15255381
TI  - Integrated HIV prevention and care strengthens primary health care: lessons from
      rural Haiti.
AB  - Three decades ago, the world's ministries of health declared primary health care-
      the delivery of basic preventive and curative services--a top priority. Since
      then, however, the world's poorest countries have not met most primary health
      care goals. Twenty-six years after the Declaration of Alma Ata, we are said to be
      living in a time of "limited resources," a phrase that construes various health
      interventions as competing priorities. As HIV has become the leading infectious
      cause of adult death in much of the world, it is difficult to argue that AIDS
      prevention and care are not ranking priorities for primary health care, yet
      precisely such arguments have held sway among international health policy makers.
      We present new information emerging from the scale-up of an established and
      integrated AIDS prevention-and-care program, based initially in a squatter
      settlement in central Haiti, to a second site in rural Haiti. The program
      includes robust prevention efforts as well as community-based therapy for
      advanced AIDS; three related components--women's health and active case finding
      and therapy for tuberculosis and sexually transmitted infections--were central to
      this effort. We tracked changes in key indices over the 14 months following the
      introduction of these services to a public clinic in central Haiti. We found that
      integrated AIDS prevention and care, including the use of antiretroviral agents,
      to be feasible in resource-poor settings and that such efforts may have favorable
      and readily measured impact on a number of primary health care goals, including
      vaccination, family planning, tuberculosis case finding and cure, and health
      promotion. Other collateral benefits, though less readily measured, include
      improved staff morale and enhanced confidence in public health and medicine. We
      conclude that improving AIDS prevention and treatment can help to reinvigorate
      flagging efforts to promote universal primary health care.

PMID- 15255382
TI  - Spreading effective AIDS care in poor countries, thoughts on the Partners-in
      Health/Zanmi Lasante experience in Haiti.

PMID- 15255383
TI  - Internet sales of tobacco: heading off the new E-pidemic.
AB  - Tobacco vendors are a growing presence on the internet. We describe the business
      appeal of the internet to tobacco retailers, including interviews with industry
      insiders that reveal the marketing goals and strategies of tobacco companies and
      highlight the potential future risks to tobacco control efforts. In countering
      these tactics, tobacco control advocates should not limit themselves to legal and
      regulatory remedies, but should also use the power of the internet to their own
      advantage. We suggest methods to combat the growing number of sites devoted to
      tobacco sales. These strategies could be used to limit both consumer access to,
      and sales effectiveness of, these sites.

PMID- 15255384
TI  - Regulation of vaccines: strengthening the science base.
AB  - This paper aims to review the history of development of vaccine regulatory
      approaches, to assess practices that may be barriers to access to innovative
      products, and to suggest possible approaches to address these practices. Despite
      the appearance of new vaccines in the past few years, many vaccines are based on
      old technologies, and are still subject to regulatory practices devised many
      years ago. Vaccine regulation began with a foundation on vaccine testing, and
      only in response to tragedies associated with vaccine use did new concepts begin
      to be defined. Vaccine regulation now includes a range of functions that cover
      the entire continuum of vaccine development and use. However, some regulatory
      practices, such as the continuing dependence on outdated animal tests, have not
      kept pace with these changes. Other practices, such as the continual raising of
      the standard of Good Manufacturing Practice (GMP) compliance, or the move to
      increasingly larger phase 3 clinical trials, appear to be based more on perceived
      risks than on firm scientific principles. The future of effective regulation for
      vaccines that will allow innovation while protecting the public health must be
      based on three guiding principles: a firm science base for policies and
      decisions, a risk-based approach to implementation of regulatory oversight, and
      support for regulatory research to inform these activities. These should be
      implemented in a setting of international harmonization.

PMID- 15255385
TI  - The voice of the public in public health policy and planning: the role of public
      judgment.
AB  - Community involvement with public health planning and implementation are vital to
      improving community health. There are a variety of community health models that
      are available. We describe these four models from the perspective of how they
      involve the broader community. These models are evaluated from a different
      perspective about linking the community and politics and agencies, that involves
      naming issues, framing options, public deliberation and public acting. We suggest
      ways that these models can be further refined to connect citizens to the
      processes that we use for community health improvement.

PMID- 15255386
TI  - Biomedicalization and alcohol studies: implications for policy.
AB  - The reduction of alcohol problems to genetic and biological processes is not new;
      however, biomedicalization is progressively dominating how alcohol issues are
      viewed in the U.S. This paper illustrates the process of biomedicalization in the
      alcohol field by examining: 1) the organizational move of the National Institute
      on Alcohol Abuse and Alcoholism (NIAAA) to the National Institutes of Health in
      1992; 2) the emphasis on biomedical goals in NIAAA's five-year Strategic Plan; 3)
      increased NIAAA funding of biomedical research from 1990-2002; and, 4) trends in
      the growing proportion of biomedical information provided in NIAAA's Reports to
      Congress. The implications of this dominance of the biomedical approach on policy
      are profound. As biomedicalization prevails as a dominant lens by which alcohol
      problems are framed, policymakers will tend to move towards individualistic
      solutions to social problems. Broader community and societal based efforts to
      understand and control alcohol problems may be increasingly replaced by a focus
      on individuals thereby omitting important environmental factors.

PMID- 15255387
TI  - Comments on "Preventing illegal tobacco and alcohol sales to minors through
      electronic age-verification devises".

PMID- 15255388
TI  - Introduction: a new and innovative implant design.

PMID- 15255389
TI  - AICRG, Part I: A 6-year multicentered, multidisciplinary clinical study of a new
      and innovative implant design.
AB  - PROBLEM: Repetitive microstrains, which occur at the bone-implant interface
      during function, can lead to implant loss. In an attempt to improve survival by
      directing the stresses during function away from the dense cortical bone and
      toward the resilient trabecular bone, the Ankylos implant was developed with a
      roughened, progressive thread and a smooth cervical collar. The highly polished
      collar reduces the stresses in areas of the crestal bone. A precisely machined
      Morse taper prevents rotation of the abutment on the implant and eliminates the
      microgap present in many 2-stage implant systems. Clinical studies of other
      implants at different clinical research centers have demonstrated varying degrees
      of survival. PURPOSE: The purpose of this paper was (1) to assess the overall
      clinical survival of this new implant design and (2) to compare implant stability
      (ie, Periotest values [PTVs]) over time with other implants. METHOD: The
      investigation represented a comprehensive, multicentered, international clinical
      study conducted over a period of 6 years. It was conducted under an
      Investigational Device Exemption (IDE) protocol that was reviewed and accepted in
      the United States by the Food and Drug Administration (FDA). Over 1500 implants
      were placed and restored, and follow-up data were gathered for a period of up to
      3 to 5 years. RESULTS: Over 44% of the clinical research centers reported no
      failures (100% survival). A total of 63% of the centers had none or only 1
      failure during the study. One center reported 6 failures in 1 patient, which were
      not related to the implant design. Overall survival for implants in function for
      3 to 5 years was 97.5%. Using failure criteria of earlier studies of other
      implants, 5-year survival was 98.3%. Higher handpiece speeds were associated with
      an increase in the number of failures. This new design produced a slightly more
      resilient trabecular bone-implant complex with a difference of about 1 PTV in all
      bone densities when compared with other implants. CONCLUSIONS: The following
      conclusions can be made: (1) the implant design was effective under all clinical
      conditions; (2) no significant and unexpected complications or risk factors were
      evident; (3) survival was found to be excellent; and (4) this implant is well
      suited for use in the restoration of masticatory function and esthetics in
      patients with missing natural teeth.

PMID- 15255390
TI  - AICRG, Part II: Crestal bone loss associated with the Ankylos implant: loading to
      36 months.
AB  - PROBLEM: The Ankylos endosseous dental implant is a new implant design that will
      be available in the United States in early 2004. It features an internal tapered
      abutment connection, a smooth polished collar without threads at the coronal part
      of the implant body, and a roughened surface with variable threads on the body of
      the implant fixture. A precise, tapered, conical abutment connection eliminates
      the microgap often found in 2-stage implant systems. This microgap may allow the
      accumulation of food debris and bacteria, as well as micromovement between the
      parts during clinical function, both of which can lead to a localized
      inflammation and crestal bone loss. PURPOSE: The purpose of this section of the
      study was to assess any crestal bone loss associated with this new implant.
      METHOD: The clinical performance of this new implant design was studied under
      well-controlled clinical conditions. Over 1500 implants were placed and restored.
      The vertical crestal bone loss was measured "directly" between the time of
      implant placement and uncovering, using a periodontal probe. Serial dental
      radiographs were taken between loading, and the 12-, 24-, and 36-month follow-up
      visits to determine "indirect" crestal bone loss within a specific period.
      RESULTS: Bone loss varied among the participating centers from less than 0.5 mm
      to 2.0 mm. The largest amount of bone loss occurred between the time of placement
      and uncovering. Following loading, the mean bone loss for all implants for a
      period of 3 years was about 0.2 mm/y. CONCLUSIONS: The extent of the crestal bone
      loss after loading was minimal for patients regardless of age, gender, prosthetic
      applications, bone density, and remote or crestal incisions, as well as for
      smokers or nonsmokers. Bone loss per year is well within the guidelines of 0.2
      mm/y proposed by others.

PMID- 15255391
TI  - AICRG, Part III: The influence of antibiotic use on the survival of a new implant
      design.
AB  - PURPOSE: The American College of Surgeons guidelines suggest that complex oral
      surgery may benefit from prophylactic antibiotic coverage. The use of
      preoperative antibiotics, postoperative antibiotics, or both during implant
      placement is a widely accepted practice in the United States, whereas dentists in
      other countries rarely use antibiotics. PURPOSE: The purpose of this study was to
      determine if antibiotic coverage at the time of implant placement improves the
      survival of the Ankylos implant. METHODS: As part of a comprehensive,
      multicentered, multidisciplinary, prospective, independent, international
      clinical study, designed and coordinated in the United States by the Ankylos
      Implant Clinical Research Group (AICRG), the use of preoperative (several
      regimens) and postoperative antibiotics (yes/no) were carefully documented to
      assess their influence on improving survival. A total of 1500 Ankylos implants
      were placed and followed for a period of 3 to 5 years. The decision to use
      antibiotics and the regimen to be employed was made by the treating surgeon.
      Failure was defined as removal of the implant for any reason. All data were
      entered into a computerized database for analysis. RESULTS: The use of
      preoperative antibiotics produced no significant improvement (P = .21, Fisher's
      exact test) in survival compared with those placed without antibiotic coverage.
      There was no significant difference between the regimens defined as AHA-1990, AHA
      1997, and Peterson's recommendations. CONCLUSIONS: The results of this study
      suggest that there was little or no advantage to providing antibiotic coverage
      when placing this implant. These findings also suggest that the use of
      antibiotics for implant placement may not be as beneficial as once believed. If
      validated by other studies, the elimination of this practice for routine implant
      placement would represent a small but significant step forward in the reduction
      of unnecessary antibiotic use.

PMID- 15255392
TI  - AICRG, Part IV: Patient satisfaction reported for Ankylos implant prostheses.
AB  - PROBLEM: Although many maxillary dentures exhibit sufficient retention and
      stability for patients to adapt well to them, mandibular dentures present a major
      challenge. The introduction of the endosseous dental implant provided the
      opportunity for the patient to have esthetic replacements (implant prostheses)
      that were retentive and stable for all missing natural teeth. METHOD: This paper
      reports on the satisfaction of over 470 patients with implant prostheses
      fabricated using a new and innovative implant design (Ankylos, Dentsply-Friadent,
      Mannheim, Germany). RESULTS: A total of 1500 Ankylos implants were placed,
      restored, and followed for 3 to 5 years. Patients were asked to respond to a
      series of questions related to their satisfaction with their new replacements for
      missing natural teeth. A total of 95.6% of the patients rated chewing ability
      with Ankylos prosthesis as excellent to good; 92.2% indicated a significant
      improvement in their ability to chew; 92.6% reported overall clinical function
      much better than conventional dentures; 99.1% indicated that speech had improved
      or was not changed; 96.3% indicated hot and cold foods tasted better; 98.8%
      indicated no pain or discomfort during clinical function; 99.4% liked their new
      implant prosthesis; 98.0% would seek implant-prostheses treatment again, if
      necessary; 99.1% would recommend implant prostheses to friends and relatives; and
      98.8% indicated the advantages of Ankylos prostheses far exceeded any
      disadvantages that may exist. CONCLUSIONS: Patients indicated that they (1) were
      highly satisfied with the final results of the replacements for their natural
      teeth that were retained or supported by this new implant design, (2) would not
      hesitate to recommend this form of treatment to their friends and relatives, and
      (3) would not hesitate to seek the same treatment again if necessary in the
      future.

PMID- 15255393
TI  - AICRG, Part V: Factors influencing implant stability at placement and their
      influence on survival of Ankylos implants.
AB  - PROBLEM: Several factors influence primary stabilization of dental implants at
      placement surgery. These include implant design, bone quality, implant jaw
      location, and the use of a bone tap. PURPOSE: This report evaluates clinical data
      gathered by the Ankylos Implant Clinical Research Group (AICRG) to assess (1) the
      influence of several variables on primary stability and (2) the potential for an
      Ankylos implant (Friadent GmbH, Mannheim, Germany) that is mobile at placement to
      integrate and survive for at least 3 years of clinical function. METHODS: The
      Ankylos implant is a roughened grade-2 titanium screw. A total of 1554 implants
      were placed in 478 patients. At both the time of placement and abutment
      connection, the implants were tested for evidence of clinical mobility by
      attempting to rotate or move the implant with an application of force. Survival
      was recorded from placement and up to 36 months following placement. RESULTS: At
      placement, 2.8% were found to be mobile. In the maxillary posterior quadrant,
      6.3% were clinically mobile. Implant mobility was frequent (12.2%) in jaw regions
      with poor-quality bone (BQ-4) or with short implants (8 mm = 8.3% mobile). Of the
      implants mobile at placement, 97.7% were stable at uncovering. The 3-year
      postplacement survival of initially mobile implants was 84.1% compared with 96.8%
      for implants not mobile at placement (chi2 test, P = .001). CONCLUSIONS: The
      Ankylos implant predictably promoted primary stability during surgical placement.
      Poor bone quality, short implants, and maxillary posterior jaw locations were all
      associated with a slightly higher rate of mobility at placement. Primary implant
      stability, while highly desirable, is not absolutely necessary for achieving
      osseointegration of Ankylos

PMID- 15255394
TI  - Ankylos implant system: concept and clinical application.
AB  - PROBLEM: The Ankylos system was developed in 1985 and has been in clinical use
      since 1987. Some of its significant design features include (1) a progressive
      thread structure of the endosseous implant body for targeted load distribution to
      the apically positioned spongy bone; and (2) the gap-free subgingival tapered
      connection to the abutments. PURPOSE: The purpose of this report is to
      demonstrate that the Ankylos Implant System meets both the patients' and the
      dentists' standards of success and is suitable for use as single tooth
      replacements, bridge abutments, and retention elements for all regions and
      prosthetic indications. METHOD: The data from 5439 implants were evaluated
      between October 1991 and October 2002. The implants were considered successful if
      the following criteria were met: (1) clinical stability and function; (2) no
      inflammation of the peri-implant hard and soft tissue; (3) no progressive loss of
      the peri-implant bone; (4) no progressive loss of the peri-implant mucosa; and
      (5) satisfaction of the patient. All implants placed during this period were
      included in the evaluation as a prospective study. The average loading period was
      56.8 months. Postoperative follow-ups were made once a year by a standardized
      protocol. The results were classified by prosthetic application in Table 1. A
      total of 943 implants were placed as single tooth restoration and were followed
      for the duration of the study. RESULTS: The success rate for this type of
      restoration was 98.7%. For free-end implant restorations, there were 1679
      implants placed with a 97.9% success rate. When the edentulous area involved a
      large gap, a total of 805 implants were placed with a 97.3% success rate. For
      cases involving reduced dentition, 606 implants were used with a 95.8% success
      rate. Another significant finding was that the success rates classified by
      maxilla and mandible showed no differences.

PMID- 15255395
TI  - New prosthetic restorative features of Ankylos implant system.
AB  - PROBLEM: All oral implant systems rely on the abutment part of the implant to
      provide stability for the dental prosthetic. The Ankylos implant offers precisely
      machined, tapered-cone abutment (Morse taper) connection. This tapered abutment
      connection provides high resistance to bending and rotational torque during
      clinical function, which significantly reduces the possibilities of screw
      fracture or loosening. PURPOSE: This report describes the design and mechanical
      construction characteristics of the Ankylos implant system that make it possible
      for the system to provide final restorations that are natural looking,
      esthetically acceptable, durable, and cost effective. METHODS: Review of the
      clinical literature. RESULTS: The clinical results of singletooth crowns borne on
      Ankylos implants in the lateral tooth region are excellent after a minimum of 5
      years in function (mean = 6.3 years) compared with the high prosthetic
      complication rate with other systems. Abutment loosening occurred in only 1.3% of
      the 233 innovative implants restored with crowns that were designed with a
      physiologically shaped occlusal surface. CONCLUSION: This implant system is
      exceptionally well suited for use in the restoration of missing natural teeth.

PMID- 15255396
TI  - Present status of immediate loading of oral implants.
AB  - PROBLEM: Several conditions must be present to obtain implant integration and
      long-term clinical success when using the one-stage implant placement procedure
      with immediate loading. These conditions include (1) primary stability, (2)
      sufficient bone quality, and (3) elimination of micromovement of the implant
      before osseous integration is complete. PURPOSE: This report presents the results
      of research on immediate loading using a new and innovative implant design,
      Ankylos. METHODS: The author reviewed clinical studies of immediate loaading or
      oral implants, including two treatment options, removable overdentures and fixed
      reconstructions. RESULTS: Animal studies have demonstrated that successful
      osseointegration of Ankylos implants can occur (Figure 2D) when implants are
      placed and loaded immediately in the presence of some specific conditions. The
      histological findings involving implants that were placed in humans and
      immediately loaded showed no fibrous tissue formation (encapsulation). The bone
      to-implant contact (osseointegration) was found to be excellent between the
      immediately-loaded implants and the surrounding alveolar bone. CONCLUSION: The
      Ankylos implant system with its progressive thread design successfully promotes
      primary, clinical stability at the time of implant placement. Several animal
      studies have shown that in implant restorations placed in similar areas of poor
      bone quality (ie, maxilla and the posterior part of the mandible), the concept of
      immediate loading can result in long-term clinical success, when loading forces
      are controlled. Immobilization of the implants and soft diet recommendations that
      reduce micromovement at the bone-to-implant interface will improve long-term
      clinical success. In summary, the Ankylos implant is well designed for one-stage
      placement with immediate loading, as well as for two-stage treatment protocols.
      Both clinical protocols will result in long-term clinical survival.

PMID- 15255397
TI  - Functional and esthetic considerations for single-tooth Ankylos implant-crowns: 8
      years of clinical performance.
AB  - PROBLEM: Following the loss of an anterior natural tooth, the mucogingival
      complex begins to collapse. The early placement of endosseous dental implants can
      prevent or reduce the extent of this collapse. If there is a long interval
      between the loss of the natural tooth and the placement of the implant prosthetic
      replacement, this collapse tends to increase significantly. PURPOSE: This paper
      will report on the clinical success of this implant product in the fabrication of
      esthetic, functional, and harmonious replacements for missing single, natural
      teeth for a period of 8 years. METHOD: A total of 275 single Ankylos implant
      tooth restorations in the anterior and posterior jaw regions were placed and
      monitored for 8 years. Of these, 264 implants were restored using the titanium
      Balance abutments, and only 11 were restored using ceramic abutments. The final
      restorations were either metal-ceramic or full-ceramic crowns and were cemented
      with glass ionomer cement. RESULTS: The survival rate was 98.2%, with only 5
      implants being lost during the healing phase. There were no other implant losses
      in the postloading period that averaged 3.2 years. To date, there have been no
      mechanical complications associated with the prosthetic components (ie, screw
      loosening, screw breaking, or crown breaking) for either the titanium or the
      ceramic abutments. CONCLUSIONS: Experience with the Ankylos system with single
      tooth replacement indications may be considered positive with regard to the
      esthetic and functional results of the treatment. The lack of mechanical
      complications and problems with the hard and soft tissue in the loading phase of
      the implants suggests the functional safety of the tapered connection between
      implant and abutment.

PMID- 15255399
TI  - Leprosy rehabilitation--a shared responsibility.

PMID- 15255398
TI  - Rehabilitation of leprosy-affected persons.

PMID- 15255400
TI  - Answering the rehabilitation needs of leprosy-affected persons in integrated
      setting through primary health care services and community-based rehabilitation.
AB  - This article aims to discuss the strategies for answering the rehabilitation
      needs of persons with leprosy-related disabilities in integrated settings through
      primary health care (PHC) services and community-based rehabilitation (CBR).
      While the provision of rehabilitation services through the PHC system remains
      problematic in most developing countries, the article concludes that CBR
      programmes have the potential for rehabilitation of leprosy-affected persons in
      integrated settings. However, the limited coverage of CBR programmes may pose an
      obstacle to such an approach. The author suggests the use of existing specific
      rehabilitation infrastructures meant only for leprosy-affected persons for
      initiating, sustaining and extending the CBR coverage to the surrounding
      communities. At the same time, the author asks for support and strengthening of
      organizations of leprosy-affected persons, promoting their active involvement in
      all rehabilitation processes.

PMID- 15255401
TI  - The changing face of rehabilitation in leprosy.

PMID- 15255402
TI  - Knowledge and management of disabling conditions in South Asian histories:
      implications for leprosy futures.
AB  - Elimination of leprosy as a public health problem appears feasible in South Asia
      in the present decade through multi-drug therapy, but management of disability in
      cured leprosy patients will continue through the 21st century, probably with some
      ongoing stigma. This paper provides new perspectives on leprosy-related
      disabilities by reviewing the historical careers of four disabling conditions
      sharing some features with leprosy: lathyrism, iodine deficiency disorders (IDD),
      cataract and poliomyelitis. All are targeted for eradication or serious reduction
      using affordable surgery or preventive measures, yet they have proved
      unexpectedly resilient. Technical solutions alone bring only partial success.
      There is a need also for community-based delivery methods, individual and family
      self-help, and some redeployment of professional expertise.

PMID- 15255403
TI  - Rehabilitation of leprosy-affected persons: a response to Dr Srinivasan's
      article.

PMID- 15255404
TI  - Rehabilitation of the leprosy-cured: some comments.

PMID- 15255405
TI  - Some suggestions for implementing rehabilitation of leprosy-affected persons in
      Tamil Nadu.

PMID- 15255406
TI  - Prospective: Seniors confused, skeptical about Medicare changes.

PMID- 15255407
TI  - Casebook: epileptic seizures and turns.

PMID- 15255408
TI  - Casebook: the dizzy patient.

PMID- 15255409
TI  - Key developments in neurology.

PMID- 15255410
TI  - The GP's role in acoustic neuroma.

PMID- 15255411
TI  - The management of orofacial pain.

PMID- 15255412
TI  - The patient with Parkinson's disease.

PMID- 15255415
TI  - Hormonal replacement therapy: quo vadis?

PMID- 15255413
TI  - The management of peptic ulcer disease.

PMID- 15255416
TI  - Our osteoporosis report card: 'A' for apathy, 'D' for effort, and 'F' for
      results.

PMID- 15255417
TI  - Diagnosis and evaluation of patients with osteoporosis.

PMID- 15255418
TI  - Peripheral bone densitometry.

PMID- 15255419
TI  - Low bone mineral density in premenopausal women.
AB  - With the proliferation of bone densitometers, an increasing number of
      premenopausal women are having their bone density tested. Approximately 15% of
      premenopausal women have bone mineral density that is more than 1 standard
      deviation less than the young-adult mean, and approximately 0.6% are more than
      2.5 standard deviation below young-adult mean bone density. Most premenopausal
      women with low bone density have low peak bone mass, stable bone density, and low
      short-term absolute risk of fracture. The management of these patients involves
      nonpharmacologic lifestyle measures and reassurances that fracture risk is low. A
      minority of premenopausal women with low bone density have increased short-term
      absolute fracture risk with contributing diseases, conditions, or medications
      that should be identified and treated. Premenopausal women with fractures are at
      increased risk for fractures later in life. Methods for evaluating these patients
      and selecting those who require additional care are reviewed.

PMID- 15255420
TI  - Osteoporosis self-management: Choices For Better Bone Health.
AB  - Despite recent pharmacologic advances in the prevention and treatment of
      osteoporosis, the disease remains incurable. Effective disease management
      ultimately lies in the hands of the individual patient, who must take
      responsibility for key health behaviors related to bone health. One behavior
      modification strategy that has proven effective, but which has not previously
      been applied to osteoporosis, is "self-management." This article describes the
      principals, evolution, and initial outcomes of a new self-management program,
      Choices For Better Bone Health. Choices is a group education course directed to
      postmenopausal women who are at risk or already affected by osteoporosis, and has
      shown positive results in early evaluations.

PMID- 15255421
TI  - Prevention of glucocorticoid-induced osteoporosis.
AB  - Patients taking low-dose glucocorticoids for 3 months or more are at risk for
      rapid bone loss. The loss may be as high as 15% in the first 3 to 6 months of
      treatment, and can lead to osteoporotic fractures, with an increase in morbidity
      and mortality. This article discusses an evidence-based approach to the
      prevention of glucocorticoid-induced osteoporosis.

PMID- 15255422
TI  - Nutrition care of older adults with chronic disease: attitudes and practices of
      physicians and patients.
AB  - OBJECTIVES: Eighty percent of older adults have at least one chronic disease.
      Most conditions could be improved with nutritional intervention. This scientific
      study assessed physician and patient knowledge of, and behaviors about nutrition,
      resulting in tools to guide physicians in nutrition management of chronic
      diseases. METHODS: Surveys were conducted of 300 practicing physicians and 600
      older adults to identify current attitudes and practices regarding the role of
      nutrition in chronic disease management. RESULTS: Ninety percent of physicians
      surveyed recognize the relationship between nutrition and chronic disease. Yet
      nutrition care occurs only sporadically in primary care settings. CONCLUSIONS:
      Most physicians are aware of nutrition in managing chronic disease, but a
      significant percentage do not routinely include nutrition in their practice. This
      research led to the development of tools to assist in identifying and managing
      the nutritional aspects of chronic disease.

PMID- 15255423
TI  - Application of anthropometric indices in childhood obesity.
AB  - OBJECTIVES: The purpose of this study was to determine which anthropometric index
      can best predict childhood obesity and to investigate the interrelationship
      between these anthropometric indices and metabolic abnormalities. METHODS: This
      was a cross-sectional study. In March 2000, 2005 children aged 7 to 8 from the
      first grade of primary schools in Taichung City in Taiwan were enrolled in this
      study. Data were obtained on the children's anthropometry, blood pressure, and
      serum lipid profiles. Body mass index (cutoff points by international age- and
      sex-specific body mass index [BMI]) and weight-length index (WLI) were measured.
      The t test, the chi2 test, and stepwise multivariate logistic regression were
      used. All subjects were divided into four groups: Group 1, nonobese by BMI
      definition, WLI < 1.2; group 2, obese by BMI definition, WLI < 1.2; group 3,
      nonobese by BMI definition, WLI > or = 1.2; and group 4, obese by BMI definition,
      WLI > or = 1.2. RESULTS: There were 951 girls (47.43%) and 1,054 boys (52.57%).
      The mean age was 7.3 +/- 0.4 years. The prevalence of obesity was 4.21% in girls
      and 7.87% in boys using BMI definition, and 12.83% in girls and 14.14% in boys
      using WLI definition. The prevalence of obesity revealed an increased trend with
      age in both sexes, whether by BMI or WLI definition. Group 4 had the highest
      prevalence rate of all metabolic abnormalities, except hypertriglyceridemia.
      After controlling for age and sex, and with group 1 as a reference, odds ratios
      were considerably higher in group 3 for the risk of hypertension (2.73; 95%
      confidence interval [CI], 1.67-4.44) and hypertriglyceridemia (5.83; 95% CI, 1.42
      23.95). Odds ratios were considerably higher in group 4 for the risk of
      hypertension (3.75; 95% CI, 2.31-6.07) and high level of low-density lipoprotein
      cholesterol (1.93; 95% CI, 1.32-2.82). CONCLUSIONS: The prevalence of obesity
      apparently differs depending on the definition of estimation. Childhood obesity
      exhibits significant correlation with some metabolic abnormalities. We
      hypothesize that, at present, both indices, BMI and WLI, should be used together
      to define childhood obesity in clinical practice until a more appropriate and
      excellent index can be established.

PMID- 15255424
TI  - Body weight status, dietary habits, and physical activity levels of middle school
      aged children in rural Mississippi.
AB  - OBJECTIVES: Obesity and cardiovascular diseases are more prevalent in the
      Southeast as compared with other geographic regions of the United States.
      However, few investigations have addressed health disparities among children in
      rural Southeastern areas. The purpose of this investigation was to determine the
      risk of overweight and obesity in middle school-aged children residing in a
      racially diverse rural community, and to characterize their dietary and physical
      activity habits. METHODS: Two hundred and five middle school children from Scott
      County, Mississippi were enrolled in this investigation. Measurements included
      height, weight, body mass index, dietary intake using a 24-hour recall, and
      physical activity level using pedometers. RESULTS: Of the 205 children studied,
      54% were "overweight" or "at risk for overweight" according to a body mass index
      for-age sex-specific percentile. Intake of saturated fat and sodium exceeded
      recommended levels, whereas intake of calcium, fruits, and vegetables was
      inadequate. One third of the sample consumed 12 fluid ounces or more of soda on
      the day of the recall. Physical activity level was below that previously reported
      for children in this age range, and knowledge of the importance of diet and
      physical activity in the prevention of cardiovascular disease was poor,
      particularly among African-American children. CONCLUSIONS: The children in our
      sample are at increased risk for overweight and obesity. Factors that may be
      targeted for intervention include a reduction in dietary intake of fat, saturated
      fat, sodium, and soft drinks, and an increased intake of fruits and vegetables.
      Physical activity should be encouraged. Many of these factors could be improved
      through changes within the school environment.

PMID- 15255425
TI  - Which anthropometric indices best predict metabolic disorders in Taiwan?
AB  - OBJECTIVES: The aim of this survey was to assess the association between the
      three simple anthropometric indices (body mass index [BMI], waist-to-hip ratio
      (WHR), and waist circumference [WC]) and various metabolic disorders, and to
      identify which indices can best predict metabolic disorders in Taiwan. METHODS: A
      cross-sectional hospital-based survey was carried out from January to December
      2000. We retrospectively analyzed the medical records of all the patients
      receiving periodic health examination with scheduled items at China Medical
      University Hospital. Anthropometric indices, metabolic profiles, and abdominal
      sonography were performed. A total of 746 people aged 19 to 87 were recruited as
      subjects for this study. The t test, chi2 test, and stepwise multivariate
      logistic regression were used. RESULTS: The subjects included 44.5% women and
      55.5% men, with a mean age of 50.74 +/- 12.68 years. After controlling for the
      other covariables, stepwise multivariate logistic regression showed considerable
      statistical significance between overall obesity and hypertension,
      hypertriglyceridemia, hyperuricemia, and fatty liver. There is also statistical
      significance between abdominal obesity and abnormal ratio of total cholesterol
      HDL (high-density lipoprotein), hyperuricemia, and fatty liver. None of the
      indices revealed any association with hyperglycemia, hypercholesterolemia,
      abnormal low-density lipoprotein, or abnormal HDL. CONCLUSIONS: BMI and WC can
      best predict some metabolic disorders. For practical reasons, the combined
      measurement of BMI and WC is the simple and inexpensive anthropometric index for
      primary health care settings in the routine physical examinations of adults. We
      hope this study can establish the background data for further investigation on
      the epidemiology of anthropometric indices in Taiwan.

PMID- 15255426
TI  - Molecular epidemiologic surveillance of salmonellosis in Arkansas.
AB  - OBJECTIVES: Salmonella serotype Newport and Salmonella serotype Typhimurium are
      the most commonly identified serotypes of Salmonella causing human disease in the
      state of Arkansas. The purpose of our study was to compare the results of
      standard and molecular epidemiologic methods of investigating human salmonellosis
      cases due to Salmonella serotype Newport and Salmonella serotype Typhimurium.
      METHODS: All isolates of Salmonella serotype Newport and Salmonella serotype
      Typhimurium collected and submitted to the Arkansas Department of Health between
      July 1, 1997 and June 30, 1998 were gathered and underwent pulsed-field gel
      electrophoresis (PFGE). Patients from whom the isolates were collected were
      contacted and completed a questionnaire. RESULTS: There were 84 patients from
      whom Salmonella serotype Newport was isolated and 83 from whom Salmonella
      serotype Typhimurium was isolated during the study period. In the 124 patients
      (74%) who completed the questionnaire, Salmonella serotype Newport was more
      likely to be the infecting agent in younger, white, and pet-owning patients (P <
      0.05). The use of PFGE confirmed that approximately 20% of the organisms had
      genetic fingerprint patterns identical to those of at least one other individual
      in the state. One third of the patients from whom these isolates were obtained
      were linked by standard epidemiologic methods. CONCLUSIONS: The use of PFGE on
      our state's most common isolates provides additional confirmation that despite
      being linked by time of onset and location of residence, the majority of the
      human salmonellosis cases in our region are still sporadic. Low-level,
      intermittent transmission of these organisms through environmental contamination
      and contact with asymptomatically infected individuals would be likely vehicles
      of transmission in our state. Molecular techniques are important in surveillance
      systems that investigate human salmonellosis. Eighty-one percent of the
      Salmonella serotype Newport and 92% of the Salmonella serotype Typhimurium cases
      that appeared to be outbreak-related based upon time of onset and location were
      actually found not to be outbreak-related by PFGE. Using techniques such as PFGE
      will allow for more focused evaluations of potential outbreaks and will save the
      already limited financial and human resources that would otherwise be spent on
      investigations that are not warranted.

PMID- 15255427
TI  - An unusual cause of hypercalcemia.
AB  - We describe a case of pronounced symptomatic hypercalcemia as a consequence of
      thyrotoxicosis alone. Primary hyperparathyroidism and other secondary causes of
      hypercalcemia were excluded. Hypercalcemia completely abated after treatment of
      thyrotoxicosis. Notwithstanding that hypercalcemia is an unusual manifestation of
      hyperthyroidism, asymptomatic elevation of serum calcium concentration had been
      documented in up to one-fourth of patients with proved hyperthyroidism. The
      current case is unusual in that the patient demonstrated a significant degree of
      hypercalcemia secondary to hyperthyroidism alone, with a serum calcium level as
      high as 3.14 mmol/L. We further discuss the putative pathophysiology of this
      "thyroid bone disease," highlighting the repercussion on calcium and bone
      metabolism in hyperthyroidism.

PMID- 15255428
TI  - Renal failure and hypercalcemia as initial manifestations of extrapulmonary
      sarcoidosis.
AB  - Sarcoidosis is a granulomatous, multisystem disease. Rarely, sarcoidosis may
      present with both renal failure and hypercalcemia. A 27-year-old black man
      presented with severe abdominal pain and renal failure. A kidney biopsy
      demonstrated features of both interstitial nephritis and membranous
      glomerulopathy thought to be secondary to nonsteroidal anti-inflammatory drugs.
      His renal function and symptoms improved with short-term prednisone therapy.
      Discontinuation of steroids led to a recurrence of renal failure and severe
      hypercalcemia. On the basis of an elevated angiotensin-converting enzyme level of
      160 U/L and anemia, a bone marrow biopsy was performed. Acid-fast bacillus
      negative, noncaseating granulomas suggested the diagnosis of sarcoidosis. The
      patient recovered after restarting prednisone. Sarcoidosis may cause both
      interstitial and membranous nephritis from direct infiltration. Hypercalcemia
      results from increased calcium absorption secondary to 1,25-dihydroxyvitamin D
      production by sarcoid granulomas. Sarcoidosis must be considered in the
      differential diagnosis of renal failure in black patients. Serum calcium and
      angiotensin-converting enzyme levels may aid the diagnosis.

PMID- 15255429
TI  - Vancomycin therapy and the progression of methicillin-resistant Staphylococcus
      aureus vertebral osteomyelitis.
AB  - Vancomycin therapy is the standard treatment for methicillin-resistant
      Staphylococcus aureus (MRSA), the most common cause of vertebral osteomyelitis,
      an increasingly frequent complication of nosocomial bacteremia. We report five
      recent cases suggesting that, while giving the appearance of success by
      conventional clinical and laboratory criteria (eg, resolution of fever and
      leukocytosis), vancomycin monotherapy may in fact be insufficient to prevent or
      reverse the progression of hematogenous MSRA vertebral osteomyelitis. A review of
      the literature and possible therapeutic alternatives are also discussed.

PMID- 15255430
TI  - Plasma cell granuloma of the thyroid and Hashimoto thyroiditis.
AB  - Plasma cell granuloma of the thyroid is a rare tumor-like lesion formed by a
      localized proliferation of inflammatory cells, supported by a stroma of fibrous
      tissue. Few cases have been previously reported in the medical literature. We
      report a new case of a 41-year-old man presenting a goiter with primary
      hypothyroidism (thyroid-stimulating hormone, 70 mIU/L; free thyroxine, < 0.01
      pmol/L; triiodothyronine, 0.66 nmol/L) and elevation of thyroid antibodies.
      Several fine-needle aspiration biopsies of the thyroid were fruitless and total
      thyroidectomy was performed. Histologic and immunohistochemical study
      demonstrated the polyclonal nature of the cells and yielded a diagnosis of plasma
      cell granuloma. Histologic findings of Hashimoto thyroiditis were present too.

PMID- 15255431
TI  - Livedo reticularis: a rare manifestation of Graves hyperthyroidism associated
      with anticardiolipin antibodies.
AB  - Livedo reticularis is a common presentation of the anticardiolipin syndrome.
      Although the presence of anticardiolipin (aCL) antibodies was previously reported
      in association with both Graves disease and Hashimoto thyroiditis, I am aware of
      no previous report of livedo reticularis in patients with Graves disease. A 29
      year-old woman presented with very active Graves thyrotoxicosis. Physical
      examination revealed, in addition to signs of very active hyperthyroidism, marked
      livedo reticularis on both her legs. Laboratory tests confirmed the clinical
      impression regarding her thyroid activity and revealed prolonged prothrombin time
      (and partial thromboplastin time) and elevated levels of both immunoglobulin G
      and immunoglobulin M aCL antibodies. After methimazole-induced remission, livedo
      reticularis completely disappeared and the levels of aCL antibodies decreased to
      within the low range of normal. The literature on aCL antibodies and autoimmune
      thyroid diseases is reviewed and the interaction between the occurrence of aCL
      antibodies, disease activity, and drug therapy in Graves disease is discussed.

PMID- 15255432
TI  - Thyroid storm and ventricular tachycardia.
AB  - A 34-year-old woman was brought to our emergency department because of sudden
      loss of consciousness. Ventricular tachycardia and fibrillation were noted on
      electrocardiographic monitoring and reverted to sinus rhythm after repeated
      defibrillation. She was treated as a case of thyroid storm. Although tachycardia
      and fever normalized after 2 days, she remained comatose and died. This is an
      unusual case because the patient's initial presentation was cardiac arrest
      without previous history of cardiac disease. To our knowledge, this is the first
      reported case where ventricular tachyarrhythmia was the initial presenting sign
      of thyroid storm.

PMID- 15255433
TI  - Thyroid storm induced by strangulation.
AB  - Thyroid storm most often occurs in patients with known thyrotoxicosis. This
      report discusses a severe case of thyroid storm developing as a direct result of
      strangulation in a patient without a preexisting history of thyroid disease.
      Classification and treatment of this entity are discussed.

PMID- 15255434
TI  - Water intoxication presenting as a suspected contaminated urine sample for drug
      testing.
AB  - A patient was evaluated medically after submitting a urine sample for drug
      screening that was considered inappropriately dilute. Although it was thought
      that the dilute urine was the result of purposely adding water, the medical
      evaluation revealed that the patient had chronic water intoxication from a very
      strict weight loss regimen. The effect of dietary solute intake on water
      metabolism by the kidneys and the development of hyponatremia are discussed.

PMID- 15255435
TI  - Erythema multiforme associated with candesartan cilexetil.
AB  - Candesartan cilexetil is an angiotensin II receptor antagonist that is widely
      used in the treatment of hypertension. It is generally well tolerated and rarely
      has adverse effects. We report the case of a 50-year-old man with a 3-year
      history of hypertension that was difficult to manage because of intolerance to
      multiple medications. Treatment with candesartan cilexetil was initiated, and
      blood pressure control improved markedly. Five weeks later, the patient presented
      with a 2 x 3-cm ulcerative plaque covered with a fibrinous exudate on the right
      upper lip. Findings from a biopsy of the upper lip were diagnostic for erythema
      multiforme. Treatment with candesartan cilexetil was discontinued, and the
      lesions resolved completely within a few weeks. To our knowledge, this is the
      first report of erythema multiforme induced by the antihypertensive medication
      candesartan cilexetil.

PMID- 15255436
TI  - Toothpastes: revisited and revised?

PMID- 15255437
TI  - An evaluation of sealing ability of endodontic materials as root canal sealers.
AB  - An in vitro dye leakage study was carried out to compare the apical microleakage
      of vitapex (calcium hydroxide based paste) when used with single gutta percha
      cone with that of dentalis KEZ (calcium hydroxide and zincoxide eugenol based
      sealer) and zincoxide-eugenol sealer when used with laterally condensed gutta
      percha obturation technique. One hundred single rooted human anterior teeth were
      instrumented and randomly divided into three experimental groups of 30 teeth each
      and two control groups of 5 teeth each. Teeth in the first group were obturated
      using a single master gutta percha cone and vitapex as root canal sealer and
      those of second group were obturated with laterally condensed gutta percha using
      dentalis KEZ as sealer. Third experimental group was filled with laterally
      condensed gutta-percha using zinc-oxide eugenol as sealer. Teeth were then
      suspended in 2% methylene blue. After this, teeth were demineralized dehydrated
      and cleared. Linear dye penetration was determined under stereomicroscope (x10)
      with calibrated eye piece. Results of this study showed that calcium hydroxide
      based endodontic material leaked comparatively less as compared to zinc oxide
      Eugenol sealer. Vitapex with single gutta-percha cone provided an adequate apical
      Seal against dye penetration.

PMID- 15255438
TI  - Secondary bone grafting in cleft lip and palate with eruption of tooth into the
      graft: a case report.
AB  - Secondary bone grafting in cleft lip and palate patients is performed preferably
      before the eruption of permanent canine in order to provide adequate periodontal
      support for eruption and preservation of the teeth adjacent to the cleft.
      Presented here with is a case of unilateral cleft lip and palate, which was
      followed up from birth to 15 years of age. The role of an orthodontist in the
      team approach for management of such anomalies is described. Also discussed in
      detail is the entire range of treatment procedures the child underwent,
      especially the role of secondary bone grafting.

PMID- 15255439
TI  - A comparative evaluation of the tensile strength of silver soldered joints of
      stainless steel and cobalt chromium orthodontic wires with band material--an in
      vitro study.
AB  - The present study was conducted to compare and evaluate the tensile strength of
      silver soldered joints of stainless steel and cobalt-chromium orthodontic wires
      with band material. An attempt was made to observe the effect of joint site
      preparation by incorporation of tack welding and increasing metal to metal
      surface contact area by flattening an end of the wire prior to soldering along
      with the regularly used round wires without tack welding. A total of 180 wire
      specimens were soldered to 180 band specimens. Fifteen samples according to joint
      site preparation were included for each of the wire groups i.e. Gloria (S.S.),
      Remanium (S.S.) and Remaloy (Co-Cr) wires of 0.036" in diameter. The findings of
      the study were suggestive that all three wires may be used for preparing silver
      soldered joints irrespective of the quality of the wire. However, when subjecting
      the wire to joint site preparation, Gloria (S.S.) wire showed less tensile
      strength as compared to Remanium and Remaloy.

PMID- 15255440
TI  - Bilateral parotid swelling in a child--a case report.
AB  - Numerous causes for bilateral parotid swellings have been identified. It must be
      assumed that systemic factors play a key role, thereby the attainment of a
      definitive diagnosis requires a familiarity with full range of possible
      etiologies for these swellings. Differential diagnostic skills must be
      implemented to achieve a precise diagnosis. A case of bilateral parotid swelling
      in a child is presented and differential diagnosis is discussed.

PMID- 15255441
TI  - Chronic mucocutaneous candidiasis: a case report.
AB  - Chronic mucocutaneous candidiasis is a immuno deficiency disorder primarily due
      to T cell dysfunction characterized by persistent candidal infection of mucous
      membrane, skin, scalp and nails. Chronic mucous membrane candidiasis has an onset
      in infancy or childhood; the primary affected site is the oral cavity; however,
      lesions may occur on trunk, hands, feet and scalp. This paper describes a 12-year
      old girl with candidial infection of the oral mucosa and extra oral involvement
      of fingers, nails, toes and intertragus area.

PMID- 15255442
TI  - Comparative evaluation of lyophilized freeze dried platelet derived preparation
      with calcium hydroxide as pulpotomy agents in primary molars.
AB  - The aim of this study was to compare the efficacy of lyophilized freeze dried
      platelet derived preparation with calcium hydroxide as pulpotomy agents in
      primary molars. Fifty six primary molars in 28 children were treated by a
      conventional pulpotomy technique. 28 teeth were treated by lyophilized freeze
      dried platelet derived preparation and another 28 by calcium hydroxide. Clinical
      evaluation was carried out out at 1, 3, and 6-months interval and the
      radiographic evaluation was carried out at 1 and 6-months. The success rate of
      lyophilized freeze-dried platelet derived preparation proved better than calcium
      hydroxide.

PMID- 15255443
TI  - Labial talon cusp on permanent central incisor: a case report.
AB  - Talon cusp is a supernumerary crown structure, a developmental disturbance in the
      shape of teeth that causes various diagnostic, functional and esthetic problems.
      Some synonyms for talon cusp are dens evaginatus of anterior teeth, interstitial
      cusp, tuberculated tooth, odontoma of the axial core type, evaginated odontoma,
      enamel pearl, supernumerary cusp etc. The lingual location on incisors, which
      frequently affects occlusion, is pathognomonic of the talon cusp. This report
      describes a rare odontogenic, isolated anomaly rather than an integral part of
      any disorder, a case of talon shaped cusp projecting from the labial surface of a
      maxillary permanent central incisor.

PMID- 15255444
TI  - A comparative evaluation of an ultrasonic and a manual toothbrush on the oral
      hygiene status and stain removing efficacy.
AB  - The efficacy of ultrasonic toothbrush and a manual toothbrush was compared on the
      oral hygiene status and on microbial parameters. 26 dental students from the
      College of Dental Sciences Davangere, Karnataka, were selected for this single
      blind study of 4 weeks duration. The participants were in the age group of 18-25
      years. The brushes were randomly allotted by the co-investigator, who also
      supervised the brushing technique throughout the study period. The subjects were
      instructed to refrain from brushing their teeth for 12-14 hours prior to each
      follow up visit. The main investigator assessed all the clinical parameters at
      baseline, 14th, 21st and 28th day. Statistical analysis was carried out by an
      independent statistician who remained blind to the test products. Each of the
      tooth brushes tested, showed significant reductions in all the clinical
      parameters between 0 and 28th day. The reductions within the groups were
      significant although no significant differences between the groups were found.
      The reductions in stain index, bleeding index and gingival index was higher in
      ultrasonic toothbrush compared to manual toothbrush. It is concluded that
      ultrasonic toothbrush is safe and effective in the removal of plaque, stains,
      reduction of gingival inflammation and gingival bleeding.

PMID- 15255445
TI  - Mucus extravasation phenomenon on the alveolar ridge in neonate: a case report.
AB  - Pediatric dentists often come across lesions in neonates, the most common ones
      being Bohn's nodules and Epstein Pearls. Other common lesions seen in the oral
      cavity of neonates are congenital epulis, hemangiomas and mucus extravasation
      cysts. Mucus extravasation phenomenon is generally encountered over the lip but
      rarely seen over the alveolar ridge. Presented here is a case of a 1-month-old
      baby with a mucus extravasation cyst measuring 0.7 x 1 cm in size over the
      alveolar ridge.

PMID- 15255446
TI  - Longitudinal change in plasma total homocysteine during pregnancy and postpartum
      in Brazilian women and its relation with folate status and other factors.
AB  - Fasting plasma total homocysteine (tHcy) concentration was determined in a cohort
      of pregnant Brazilian women (n = 46) supplemented with folic acid from the second
      trimester of pregnancy. Blood samples were obtained in the first and third
      trimesters from all women, and 30-40 days postpartum from seventeen women. Plasma
      tHcy decreased during pregnancy from 10.3 to 8.7 micromol/L, and was 11.6
      micromol/L in the postpartum. Plasma and erythrocyte folate increased, consistent
      with use of the folate supplement, but decreased slightly in the postpartum,
      whereas the opposite occurred for plasma vitamin B12. tHcy was inversely
      correlated with plasma and erythrocyte folate in the third trimester (r = -0.585
      and -0.460, respectively). This relationship occurred despite the fact that all
      women had attained what could be considered adequate levels of folate indices.
      Furthermore, the change (third trimester minus first trimester levels) of tHcy
      was inversely correlated (p < 0.01) with the changes in plasma (r = -0.573) and
      erythrocyte folate (r = -0.525). tHcy had no correlation in any of the periods
      tested with plasma vitamin B12, plasma albumin, hematocrit, hemoglobin, iron
      indices, dietary intakes of folate, vitamins B12 and B6, and levels of folate
      supplement.

PMID- 15255447
TI  - The effect of micronutrient deficiencies on iodine nutrition and thyroid
      metabolism.

PMID- 15255448
TI  - Relationship between serum, red cell, urinary and dietary magnesium in a middle
      aged French adult population.
AB  - Magnesium (Mg) is the second most common intracellular electrolyte; in the body.
      Few data are available in general population studies on the assessment of Mg
      status and its relationship to dietary intake. We explored the relationship
      between several biological Mg surrogates (serum, red cell, and urinary), Mg
      intake, age, alcohol intake, and mean energy intake in a large sample of French
      adults issued from the SUVIMAX study. Serum Mg was positively correlated with red
      cell Mg in men and women (r = 0.17; p < 0.001) whereas no association was found
      between urinary Mg and red cell Mg nor between urinary Mg and serum Mg. Age was
      positively correlated with serum and red cell Mg in women (p < 0.001) and
      negatively correlated with urinary Mg in both genders (p < 0.001). Finally, a
      negative correlation was found between dietary intake and red cell Mg in women (r
      = -0.06; p < 0.05). Among the biological Mg surrogates, an association was found
      between serum Mg and red cell Mg. Further investigations should be conducted in
      order to determine the role played by dietary Mg intake in the relationship
      between health status and several biological Mg measurements.

PMID- 15255449
TI  - Effect of age on plasma homocysteine concentrations in young and elderly subjects
      considering serum vitamin concentrations and different lifestyle factors.
AB  - OBJECTIVES: The aim of this study was to investigate whether an increase in total
      homocysteine (tHcy) concentration with increasing age is due to diminishing serum
      concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The
      possible influence of different lifestyle factors on tHcy concentration was
      considered. METHODS: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate,
      vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as
      well as cigarette smoking, were determined in 252 elderly subjects (60-87 years
      old) of the longitudinal study on nutrition and health status in an aging
      population in Giessen (GISELA) and 99 young adults (20-34 years old) of the study
      on health and nutrition of young adults (GEJE). RESULTS: Mean plasma tHcy
      concentrations were significantly higher in elderly than in young female subjects
      (9.7 +/- 1.9 micromol/L vs. 9.0 +/- 1.6 micromol/L, p < 0.05), but there was no
      difference between elderly and young men (10.6 +/- 2.1 micromol/L vs. 10.7 +/-
      2.6 micromol/L). No differences in tHcy were observed between young and elderly
      subjects after adjustment for serum concentrations of PLP, vitamin B-12, and
      folate. Multiple linear regression analysis revealed a significant influence of
      age only in elderly, but not in younger subjects. CONCLUSION: Higher tHcy
      concentrations in the elderly, in comparison to younger women, are due to lower
      serum concentrations of PLP, vitamin B-12, and folate, whereas within the age
      group of elderly subjects alone tHcy concentrations increase with age
      irrespective of serum vitamin concentrations.

PMID- 15255450
TI  - Red wine consumption prevents vascular oxidative stress induced by a high-fat
      meal in healthy volunteers.
AB  - In order to investigate the effect of red wine on plasma lipid and oxidative
      stress parameters after a high-fat meal, fifteen healthy volunteers were studied:
      three days after a high-fat meal with 250 mL of water, they received the same
      meal with 250 mL of red wine. During both periods, serial blood samples were
      drawn before and 2, 4, and 8 hours after the meal to evaluate plasma lipids
      (cholesterol and triglycerides; retinyl palmitate), oxidative stress (D-ROM, and
      malondialdehyde) and antioxidant (total plasma antioxidant levels and uric acid)
      parameters. During the meal without wine, plasma lipid parameters increased
      significantly, whereas plasma total plasma antioxidant levels decreased, and a
      trend toward reduction of uric acid levels was seen). A similar trend in lipid
      parameters was observed after the meal with wine; no significant difference in
      individual lipid parameter trends after a meal with and without wine was
      observed. Wine ingestion induced higher total plasma antioxidant levels and uric
      acid; malondialdehyde levels remained constant after wine ingestion. Plasma D-ROM
      showed a significant postprandial increase in both experiments, but it was
      significantly lowered after wine ingestion. Our results give evidence of
      oxidative stress following a fat-rich meal in healthy subjects, suggesting that
      ingestion of red wine during a high-fat meal significantly reduces oxidative
      stress without inducing any significant modification in postprandial lipemia.

PMID- 15255451
TI  - Nutrient supplementation as adjunct therapy in pulmonary tuberculosis.
AB  - The study examined the effect of supplementation with multivitamins and trace
      elements on microbiological and radiological recovery in patients with pulmonary
      tuberculosis. Forty-four patients aged 28-50 years were diagnosed with active
      pulmonary tuberculosis based on X-ray of the chest and smear examination of the
      sputum for the presence of acid-fast bacilli. They were all treated for six
      months with a standard anti-tuberculosis regimen that has been found to be
      effective worldwide for disease control. The subjects were randomized to receive
      either a multivitamin-trace element supplement or a placebo containing calcium.
      The two groups were matched on all relevant confounding variables. At two months
      into the treatment, the group that was supplemented with a multivitamin-trace
      element preparation showed a significant reduction in the number of individuals
      with sputum smear positive for acid-fast bacillus: two out of 22 individuals,
      compared with seven out of 22 among placebo-treated controls (p = 0.028, Fisher's
      test). It is concluded that patients with tuberculosis should be supplemented
      with a suitable micronutrient preparation that contains optimum amounts of all
      vitamins and trace elements that have been documented to enhance the immune
      response.

PMID- 15255452
TI  - Effects of beta-carotene supplementation on free radical mechanism in healthy
      adult subjects.
AB  - AIM: The objective of this study was to examine whether increasing doses of beta
      carotene supplements have effects on biological markers of lipid peroxidation in
      healthy volunteers. SUBJECTS AND METHODS: Forty-two healthy subjects were
      supplemented with 5 mg, 10 mg, 20 mg or 40 mg beta-carotene/day, respectively for
      five weeks. Plasma beta-carotene and tocopherol levels, malondialdehyde
      thiobarbituric reactive substances (MDA-TBARS), and conjugated dienes were
      determined using high-performance liquid chromatography (HPLC). Concentrations of
      ascorbic acid, uric acid, and the total antioxidative capacity (TAC) in plasma
      were measured photometrically. RESULTS: Plasma beta-carotene levels increased
      significantly according to the intervention dose (p < 0.001), and concentrations
      of tocopherol equivalents and ascorbic acid were within the physiological range
      except in the 5 mg intervention group where a significant decrease of vitamin C
      was assessed (p < 0.05). Uric acid in plasma decreased significantly in all
      groups (p < 0.05) up to the end of investigation, but was within the normal
      range. Trolox equivalent antioxidative capacity (TEAC) decreased significantly (p
      < 0.001) in all groups during supplementation. MDA-TBARS remained unchanged after
      five weeks except for the 40 mg beta-carotene substitution group, where a
      significant decrease was observed (p < 0.05). CONCLUSION: Beta-carotene
      supplementation of healthy subjects significantly increased plasma beta-carotene
      status without inducing adverse biological effects. Beta-carotene did not
      especially protect against oxidative stress, except for the 40 mg group. These
      data suggest that additional effects of beta-carotene supplementation on well
      nourished, healthy subjects are limited.

PMID- 15255453
TI  - Lutein supplements are not bioavailable in the Mongolian gerbil while consuming a
      diet with or without cranberries.
AB  - Lutein is a carotenoid that may be involved in the prevention of macular
      degeneration and is available as supplements. Cranberries are a potential
      "functional food" due to anti-adhesion and antioxidant properties. This study was
      designed to determine the bioavailability of lutein supplements in Mongolian
      gerbils, as prior studies have focused on beta-carotene, and to investigate any
      interactions between a lutein supplement and a diet containing cranberries.
      Gerbils (n = 28) were divided into treatment groups: lutein + cranberry; lutein +
      control; cottonseed oil + cranberry; and cottonseed oil + control. The lutein
      supplement (50 microg lutein in oil) was delivered orally for 14 days, and then
      blood, livers, and eyes were collected. Samples were analyzed by high-performance
      liquid chromatography (HPLC) and total antioxidant status was determined. Serum
      and liver were analyzed for lutein, retinol, and alpha-tocopherol. Serum lutein
      concentrations were extremely low in all four groups. Serum total antioxidants
      did not differ (p > 0.2) among diet groups. Serum retinol concentrations were
      significantly lower in the cranberry groups (p = 0.0024). In conclusion, gerbils
      are able to thrive on a high cranberry diet. However, this study showed that
      lutein, as a daily supplement in oil, is not bioavailable in Mongolian gerbils.

PMID- 15255455
TI  - Relation between age, ventricular arrhythmia, left ventricular hypertrophy and QT
      dispersion in patients with essential hypertension.
AB  - The aim of this study was to look at the effect of age on left ventricular
      hypertrophy (LVH), left ventricular mass (LVM), QTc dispersion and Lown score of
      arrhythmia in patients with essential hypertension compared with normal healthy
      subjects. One hundred and fifteen (115) hypertensive patients (67 men, 48 women)
      and fourty-one (41) age-matched healthy control subjects (22 men, 19 women) were
      included in the study. The Lown score, LVH and LVM prevalence were significantly
      higher in hypertensive patients compared with healthy controls. LVH and LVM were
      much higher in hypertensive and control males compared to females. While LVH and
      LVM were more prevalent in younger hypertensive patients, the reverse was seen in
      healthy control subjects, where the elderly group showed a higher prevalence. QTc
      dispersion was significantly higher in hypertensive patients compared with
      healthy controls. While QTc dispersion was significantly higher in older healthy
      controls, this was not the case in the older hypertensive patients.

PMID- 15255454
TI  - Effects of 6-month multivitamin supplementation on serum concentrations of alpha
      tocopherol, beta-carotene, and vitamin C in healthy elderly women.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of supplementation
      with nutritional doses of antioxidant nutrients on the serum concentrations of
      ascorbic acid, alpha-tocopherol, and beta-carotene in healthy elderly women.
      METHODS: The study was performed as a randomized placebo-controlled, double-blind
      trial. Two hundred forty-one free-living, healthy women aged 60 years and older
      were recruited by newspaper advertisement in Hanover, Germany and its environs.
      As 21 women dropped out, data of 220 women (aged 60-91 years median 63 years)
      were included in this evaluation. Subjects were randomly assigned to receive
      either a multivitamin/mineral or placebo capsule with identical appearance for
      six months containing 36 mg 36mg vitamin E, 150 mg vitamin C, and 9 mg beta
      carotene. Serum concentrations of vitamin C, alpha-tocopherol, and beta-carotene
      were measured initially and after six months of supplementation. Data were
      analyzed with the SPSS 10.0 program. RESULTS: Median serum concentrations of
      alpha-carotene and vitamin E increased significantly in the supplemented group
      (p=0.000), whereas no significant modifications were observed in the placebo
      group. Median vitamin C concentration of the supplemented group did not differ
      from baseline after intervention, but that of the placebo group was significantly
      decreased after six months (p=0.000). In comparison to estimated desirable serum
      concentrations of > 30 micromol/L vitamin E, 50 micromol/L vitamin C, and > 0.4
      micromol/l beta-carotene at baseline, lower concentrations were found in 21.1%,
      6.9%, and 1.0% of all subjects, respectively. After supplementation none of the
      members of the supplemented group had tocopherol concentrations below 30
      micromol/L and only one woman of the supplemented group had a serum beta-carotene
      concentration below 0.4 micromol/L. The change in serum concentrations of vitamin
      C and E in the supplemented group depended on the status at baseline. CONCLUSION:
      A six-month supplementation with physiological doses of antioxidant vitamins
      improves the blood concentration of these nutrients even in relatively well
      nourished elderly women or, as seen for vitamin C, prevents reduction of serum
      concentrations. Prevalence of suboptimal serum concentrations can be reduced.

PMID- 15255456
TI  - Efficacy of propafenone for maintaining sinus rhythm in patients with recent
      onset or persistent atrial fibrillation after conversion: a randomized, placebo
      controlled study.
AB  - OBJECTIVE: The aim of this study was to investigate the efficacy and safety of
      propafenone in the prevention of atrial fibrillation (AF) relapse after
      restoration of sinus rhythm. METHODS: This study consisted of 110 consecutive
      patients with recent onset and persistent AF. After restoration of sinus rhythm,
      patients were randomized to propafenone (n: 58, age: 60 +/- 12 years) or placebo
      (n: 52, age: 62 +/- 10 years).There were 11 withdrawals (7 in the propafenone and
      4 in the placebo group) during follow-up. Follow-up evalutations were conducted
      at the first, 3rd and then at an interval of three months during 15 months. The
      clinical characteristics in both groups were comparable. The AF relapse was
      analysed by the Kaplan-Meier method. RESULTS: At 15-month follow-up, AF relapsed
      in 20 (39%) and 31 (65%) patients in the propafenone and placebo groups,
      respectively (p = 0.015). In subgroup analysis, AF recurrence was significantly
      lower in the propafenone group than in the placebo group only in the recent onset
      AF patients with spontaneous conversion (21% vs. 61%, p = 0.01). However, the AF
      relapse rates were similar in patients with persistent AF and with recent AF who
      converted to sinus rhythm pharmacologically or electrically in the propafenone
      and placebo groups. Four patients on propafenone and one on placebo had adverse
      effects necessitating discontinuation of the drug (p = 0.36). CONCLUSION: At 15
      months, propafenone seems to be superior to placebo for maintaining sinus rhythm
      in patients with recent onset or peristent AF. This superiority originates mainly
      from patients with recent onset AF in whom sinus rhythm occurred spontaneously.
      Its adverse effects are similar to placebo.

PMID- 15255457
TI  - Influence of haematological parameters before coronary angioplasty on subsequent
      restenosis.
AB  - OBJECTIVES: Restenosis is the major limitation of coronary interventions
      occurring in nearly a third of the patients undergoing percutaneous transluminal
      coronary angioplasty (PTCA) with no single, definite predictor demonstrated in an
      individual patient. Platelets are known to play an important role in the
      pathogenesis of subsequent restenosis. METHODS AND RESULTS: In a prospective
      study, follow-up coronary angiographies were performed in 102 consecutive
      patients with stable angina who underwent a successful PTCA for single-vessel
      coronary artery disease. Demographics, baseline lipid profiles (total
      cholesterol, HDL- and LDL-cholesterol, triglycerides) and haematological
      parameters (red cell, white cell and platelet counts, haemoglobin concentration,
      haematocrite %, mean platelet volume, platelet mass and fibrinogen levels) were
      compared between patients with and without restenosis. In the restenosis group,
      mean platelet volume (8.82 +/- 0.78 fl vs. 8.13 +/- 0.64 fl, p < 0.001), white
      cell count (8673 +/- 322 x 10(3)/microl vs. 7513 +/- 232 x 10(3)/microl, p <
      0.01) and fibrinogen level (4.2 +/- 1.4 g/l vs 3.6 +/- 1.1 g/l) were
      significantly higher. The relative odds for developing angiographically defined
      restenosis were 2.49 times greater in diabetics (p = 0.11) and 2.54 times greater
      in men (p = 0.13). It is 1.43 times greater in patients with higher fibrinogen
      levels (p = 0.16). But, the relative odds for developing restenosis were 10.43
      times greater in patients with larger pre-procedural mean platelet volumes (p <
      0.01). CONCLUSIONS: There was a positive correlation between mean platelets
      volume and loss in luminal diameter between post-angioplasty and follow-up
      angiographies (r = +2.345, p = 0.01). There was no association between restenosis
      and haemoglobin, haematocrit, red cell count, white cell count, platelet count,
      platelet mass and plasma fibrinogen level. The development of restenosis after
      successful coronary angioplasty may be mainly influenced by the platelet size.

PMID- 15255458
TI  - Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic
      patients with stable ischaemic heart disease.
AB  - OBJECTIVE: Hypercholesterolaemia is associated with a loss of endothelium
      dependent vasodilation, which may facilitate the occurrence of myocardial
      ischaemia in patients with coronary artery disease (CAD). The improvement of
      endothelial dilator function after 4 to 6 weeks of oral lipid-lowering therapy
      has been documented. Whether this early restoration of endothelial function by
      statins translates into anti-ischaemic effects is unknown. This study was
      designed to determine the effect of 4 weeks' treatment with 80 mg atorvastatin
      daily on exercise-induced ischaemia in patients with stable ischaemic heart
      disease (IHD) receiving standard anti-anginal drug therapy. METHODS AND RESULTS:
      A total of 41 patients with documented CAD, exercise-induced ischaemia and LDL
      cholesterol > 130 mg/dl underwent exercise ECG, angina score and lipid level
      assessment at baseline, after 4 weeks of placebo treatment, and after 4 weeks of
      therapy with atorvastatin 80 mg. Primary endpoint was the change in time to 1 mm
      ST-segment depression (= ischaemic threshold) between placebo and treatment
      period. Atorvastatin treatment resulted in a 55% reduction of low-density
      lipoprotein (LDL) cholesterol (from mean of 162 (SD 32) to 72 (20) mg/dl). For a
      comparable rate-pressure product, the average time to 1 mm ST-segment depression
      was 295 (112) s at baseline, 314 (149) s after placebo and 301 (131) s after
      atorvastatin, indicating that the ischaemic threshold was not significantly
      modulated after 4 weeks of atorvastatin treatment. There was also no significant
      change in global angina score or in time to maximal ST-segment depression.
      CONCLUSIONS: High-dose atorvastatin treatment for 4 weeks drastically reduced LDL
      cholesterol. However, the present study did not demonstrate a significant effect
      on the ischaemic threshold in patients with stable IHD already under treatment
      with anti-ischaemic agents.

PMID- 15255459
TI  - Comparison of management and 30-day mortality of acute myocardial infarction in
      men versus women in Estonia.
AB  - OBJECTIVE: There is conflicting information about gender differences in clinical
      features, management and outcome after acute myocardial infarction (AMI). The
      objective of the study was to compare the baseline characteristics, management
      and 30-day mortality of AMI in men and women in Estonia. METHODS: This study
      included consecutive unselected patients from the Myocardial Infarction Registry
      (MIR) in Estonia, who were admitted to a university hospital between January 2001
      and February 2002. Logistic regression analysis was used to estimate crude and
      adjusted odds ratios (OR) with 95 percent confidence intervals (95% CI). RESULTS:
      The study included 228 men and 167 women. Women were older than men (73.49 +/-
      10.95 vs. 65.63 +/- 12.60, p < 0.000), and had more comorbidities. After age
      adjustment, the higher prevalence of comorbidities, like diabetes (age-adjusted
      odds ratio [OR] 2.48, 95% confidence intervals [CI] 1.45-4.24), hypertension (OR
      1.78, 95% CI 1.15-2.76) and history of congestive heart failure (OR 2.14, 95% CI
      1.32-3.46) in women was preserved. Women were more frequently treated with
      diuretics (OR 2.68, 95% CI 1.69-4.25) and less frequently with statins (OR 0.61,
      95% CI 0.39-0.96), after age-adjustment. Although thrombolytic therapy, coronary
      angiography and angioplasty were performed less frequently in women, these
      differences disappeared after age-adjustment. Female gender was not an
      independent predictor of 30-day mortality after AMI, crude OR was 1.39, 95% CI
      0.80 to 2.41, adjustment for age and other covariates reduced OR to 0.98, 95% CI
      0.44 to 2.20. CONCLUSIONS: Among AMI-patients, age but not gender is an important
      determinant of care and early mortality.

PMID- 15255460
TI  - QT dispersion in the risk stratification of patients with unstable angina:
      correlation with clinical course, troponin T and scintigraphy.
AB  - OBJECTIVE: This study sought to evaluate the potential prognostic usefulness of
      QT dispersion (QTd) in patients with unstable angina. METHODS AND RESULTS: QTd
      was calculated and plasma troponin T (TnT) level was measured and rest perfusion
      imaging with Tc-99m sestamibi was performed in 62 patients admitted with chest
      pain at rest. All patients had a follow-up during one month in order to assess
      cardiac events. Cardiac events occurred in 41 patients (no deaths, 11 myocardial
      infarctions (MI), 4 urgent and 26 planned revascularizations). The mean QTd in
      patients with cardiac events was significantly higher than in those without
      cardiac events (68 +/- 28 vs. 54 +/- 14 ms; p = 0.01). When patients were divided
      into subgroups according to the cardiac events, the mean QTd in MI and
      revascularization were 90 +/- 25 ms and 60 +/- 25 ms, respectively. QTd in
      patients with MI was higher than in patients without cardiac events (p = 0.001).
      There was no significant difference in QTd between the revascularization subgroup
      and patients without cardiac events. Nineteen patients with elevated TnT had a
      greater QTd compared to patients with normal TnT (74 +/- 29 vs. 56 +/- 20 ms; p =
      0.008). Additionally, the mean QTd in 46 patients with perfusion defects was
      slightly higher than in patients without (66 +/- 27 vs. 53 +/- 17 ms; p = 0.03).
      There was also a moderate correlation between QTd and the number of perfusion
      defects (r = 0.31, p = 0.01). On the other hand, most of the patients who had a
      MI or urgent revascularization had a QTd greater than 75 ms. CONCLUSION: The
      measurement of QTd in patients with unstable angina may help to stratify patients
      at high risk for cardiac events, in particular MI and urgent revascularization.

PMID- 15255461
TI  - C-reactive protein increase in acute myocardial infarction.
AB  - OBJECTIVE: Considering acute myocardial infarctions (AMI), data demonstrate that
      C-reactive protein (CRP) levels reflect the severity of myocardial damage and
      that high CRP level is associated with a worse outcome. This study evaluates the
      prognostic value of CRP and the determinants of its increase during AMI. METHODS
      AND RESULTS: A retrospective observational study of 126 patients with a ST
      segment elevation myocardial infarction (STEMI); 101 patients had reperfusion
      therapy (93 thrombolysis, 8 PTCA). Peak CRP (median: 3.5 mg/dl) was achieved the
      third day. A correlation existed between this peak and age (r = 0.1838; p =
      0.0408). Diabetic patients not requiring insulin showed peaks double those of
      other patients (10.4 versus 6.1 mg/dl; p = 0.0165). The peak was higher in
      anterior infarctions (anterior: 8.4, lateral: 6.9, inferior: 6.4, posterior: 3.9
      mg/dl; p = 0.0206) and for those showing a Q-wave (7.5 versus 3.9 mg/dl; p =
      0.0020). It was correlated with the CK (r = 0.246; p = 0.0188) and troponin Ic (r
      = 0.242; p = 0.0224) peaks among thrombolysed patients. There was an increasing
      relationship between the occurrence of cardiac failure and the magnitude of the
      CRP peak. An inverse linear relationship existed between the ejection fraction of
      the left ventricle and the CRP peak (r = -0.4187; p = 0.0000). CRP peak was lower
      with statins (3.8 versus 7.0 mg/dl; p = 0.0446). Fibrates were only associated
      with lower CRP levels at admission (0.6 versus 0.9 mg/dl; p = 0.0010).
      CONCLUSIONS: CRP is an indicator of the severity of STEMI. It is also an
      indicator for the occurrence of complications during hospitalization. The effect
      of statins and fibrates on CRP levels in AMI should be studied further.

PMID- 15255462
TI  - Effects of atrial pacing on coronary sinus endothelin-1 and nitric oxide levels
      in patients with myocardial bridging.
AB  - Myocardial bridging (MB) is associated with clinical and metabolic evidence of
      ischaemia. In the present study, we aimed to evaluate the extent of
      atherosclerosis and endothelial dysfunction in patients with MB. The study
      population consisted of 15 patients with MB [9 women (60%), aged 56 +/- 9 years]
      and 14 control subjects [8 women (57%), aged 54 +/- 10 years]. All patients
      underwent coronary angiography. The femoral artery and coronary sinus endothelin
      1 (ET-1) and nitric oxide (NOx) plasma levels were measured before and after
      right atrial pacing in all subjects. Also, intravascular ultrasonography was
      performed in 13 patients with MB. With right atrial pacing, coronary sinus ET-1
      levels increased significantly in patients with MB compared with baseline levels
      (5.77 +/- 6.76 versus 11.32 +/- 9.40 pg/ml, p < 0.05). The coronary sinus ET-1
      levels remained unchanged in controls with pacing (3.99 +/- 4.00 versus 4.19 +/-
      7.15 pg/ml, p > 0.05). There was no significant difference between the two groups
      according to the increase in NOx levels with atrial pacing. Ten (77%) of the 13
      patients had plaque formation in the segments proximal to the bridge with an area
      stenosis of 37 +/- 21% (12% to 75%). In patients with MB, post-pacing levels of
      coronary sinus ET-1 correlated significantly with the cross-sectional area of the
      plaque (r = 0.65, p = 0,04). Increased ET-1 levels and the pathological data of
      intravascular ultrasonography may be associated with endothelial dysfunction and
      atherosclerosis development in patients with MB. The presence of atherosclerosis
      in the proximal segments to the bridge may contribute to the myocardial ischaemia
      detected in these patients.

PMID- 15255463
TI  - Prevalence of angiographically significant coronary artery disease in patients
      with rheumatic mitral stenosis.
AB  - OBJECTIVE: In order to evaluate the prevalence of angiographically significant
      coronary artery disease (CAD) in patients with predominant mitral stenosis
      (mitral valve area < or = 1.5 cm2), coronary angiograms of the 837 consecutive
      patients with mitral stenosis (482 women and 355 men; median age = 50 years
      [ranging from 35 to 77]) were retrospectively analysed. METHODS AND RESULTS:
      Significant CAD was defined as at least 50% diameter narrowing of a major
      coronary artery. Significant CAD was detected in 63 patients (7.5%, 30 men and 33
      women). Patients with CAD were significantly older than those without CAD
      (median: 59 vs. 49 years; p < 0.0001, respectively). With respect to coronary
      risk factors, diabetes mellitus (28.6% vs. 9.4%; p < 0.0001), hypertension (46%
      vs. 16.7%; p < 0.0001) and family history of CAD (34.9% vs. 17.3%; p = 0.001)
      were significantly more frequent in the CAD+ group as compared to the CAD- group.
      Serum levels of cholesterol were significantly higher in CAD+ group as compared
      to the CAD-patients (median: 199 vs. 176 mg/dl; p = 0.003). No significant
      differences were noted between the two groups in both serum levels of HDL
      cholesterol (p = 0.12) and triglycerides (p = 0.08). Of the 63 patients with CAD,
      21 (33.3%) had angina pectoris (AP) and, in patients free of CAD, AP was present
      in 106 (13.7%). The sensitivity and specificity of AP for the presence of
      significant CAD were 33.3% and 86.3%, respectively. The positive predictive value
      of AP for the presence of CAD was 16.5% and the negative predictive value of its
      absence was 94.1%. CONCLUSION: It is concluded that routine coronary angiography
      is not necessarily indicated in predominant mitral stenosis particularly in
      patients who are younger than 40 years and have no coronary risk factors and
      typical chest pain.

PMID- 15255464
TI  - The effect of atorvastatin on platelet function in patients with coronary artery
      disease.
AB  - BACKGROUND: Lipid-lowering therapy was shown to have several beneficial effects
      in patients with coronary artery disease (CAD). AIM: The objective of this study
      was to investigate the effect of atorvastatin on platelet aggregation in patients
      with CAD. METHODS: Twenty-five hypercholesterolaemic patients who had
      angiographically proven CAD and 16 normal subjects were enrolled. All patients
      received 10 mg/day atorvastatin for two months. Anti-platelet agents were
      discontinued 15 days prior to blood sampling at the beginning and at the end of
      the atorvastatin therapy. Aggregometric curves of the platelets in response to
      ADP, collagen and epinephrine were obtained using the aggregometry
      (turbidimetric) technique. RESULTS: In patients with CAD, total cholesterol (TC)
      and LDL cholesterol (LDL-C) basal levels were measured (230 +/- 49 mg/dl, 140 +/-
      41 mg/dl, respectively). Following lipid-lowering therapy, TC and LDL-C decreased
      significantly (p < 0.05). The activation measurements of aggregometric curves
      decreased significantly compared with basal parameters in response to ADP but not
      in response to collagen and epinephrine. CONCLUSION: Lipid-lowering therapy with
      the HMG-CoA reductase inhibitor, atorvastatin, had a marked reduction effect on
      platelet aggregation.

PMID- 15255465
TI  - Diabetes mellitus as a contributor to the in-hospital mortality after acute
      myocardial infarction in Kuwait.
AB  - OBJECTIVES: First, to compare the in-hospital mortality after acute myocardial
      infarction (AMI) among diabetic versus non-diabetic patients. Secondly, to
      evaluate if this association remains the same across gender and ethnic groups.
      METHODS AND RESULTS: We used a 1:2 individually matched retrospective case
      control study. All patients admitted to Mubarak Al-Kabeer hospital in Kuwait,
      with a confirmed diagnosis of AMI during August 1997 and July 2002 made up the
      study population. All 149 patients who died during this period made up the cases.
      Two control subjects to match each case were randomly chosen from survivors,
      after hospitalization with AMI. Cases and controls were individually matched by
      age, sex and ethnicity. History of diabetes mellitus (DM) was found to be
      significantly associated with in-hospital mortality after AMI (odds ratio: 1.9,
      95% CI: 1.2-3.0). None of the other cardiovascular related histories were
      associated with mortality. Further analyses on the type of diabetes showed that
      the NIDDM (non-insulin dependent diabetes mellitus) risk of mortality was
      significantly raised after AMI. Also among women (odds ratio: 2.7, 95% CI: 1.2
      5.9), and non-Kuwaiti population (odds ratio: 3.4, 95% CI: 1.1-9.9) the risk was
      significantly elevated. CONCLUSIONS: Risk of in-hospital mortality after AMI is
      almost doubled among diabetic patients. This association was found to be
      significantly higher among NIDDM, women and non-Kuwaiti population.

PMID- 15255466
TI  - HIV-related pulmonary hypertension. From pathogenesis to clinical aspects.
AB  - HIV-related pulmonary hypertension (HIV-PH) is a cardiovascular complication of
      HIV infection that has been recognized in the last years with increasing
      frequency. HIV-related pulmonary hypertension is a clinical disorder which
      carries a bad prognosis. While a direct HIV infection of the pulmonary vessels in
      the pathogenesis of this disorder was not demonstrated, currently a
      multifactorial pathogenesis of this disease could be hypothesized.
      Echocardiography has been found to be the most useful screening imaging modality
      for the diagnosis of HIV-PH, with a high predictive negative value and a low
      positive predictive value. For this reason Doppler echocardiography is not the
      gold standard in the diagnosis of HIV-PH. The treatment of HIV-PH is complex and
      controversial. To date, no study determining the agent of choice for the
      treatment of this disease exists. Different studies have shown variable results
      in patiens with HIV-PH treated with highly active antiretroviral therapy (HAART)
      but only HAART seems not to be effective in lowering pulmonary hypertension in
      these patients, and in some patients, HIV-PH develops in spite of a previous
      HAART. It seems reasonable in HIV-PH patients that a treatment with oral
      vasodilator drugs can improve the adherence of a long-lasting and complex
      antiretroviral therapy.

PMID- 15255467
TI  - Acute myocardial infarction during pregnancy.
AB  - We describe the case of a 27-year-old primigravida with an unremarkable medical
      history and no risk factors for coronary artery disease. At 28 weeks she received
      tocolytic therapy, first with ritodrine, subsequently with nifedipine for preterm
      labour. In addition she developed an uncomplicated non-Q wave anterolateral
      myocardial infarction. A coronary angiography performed 2 days after the acute
      event was normal. The further course was uneventful with a spontaneous vaginal
      delivery at 40 weeks. We reviewed the literature concerning the incidence of
      acute myocardial infarction during pregnancy, its physiologic backgrounds and the
      possible association with use of tocolytic therapy, sympathomimetic agents in
      particular. The impact of pregnancy on maternal haemodynamics is generally
      underestimated, which makes an early diagnosis often difficult. Future research
      has to define the specific role of currently available treatment options,
      including cardiac catheterization and more recently developed pharmacologic
      interventions. Obviously, foetal considerations will greatly influence the
      selection of different approaches.

PMID- 15255468
TI  - Thrombi in left ventricular hypertrabeculation/noncompaction--review of the
      literature.
AB  - OBJECTIVE: Left ventricular hypertrabeculation/noncompaction (LVHT) is diagnosed
      when numerous, excessively prominent trabeculations and deep interventricular
      recesses are found in the left ventricle. Although it is assumed that the
      intertrabecular recesses are a location prone to thrombus formation, the
      prevalence of thrombi in LVHT hearts is unknown. METHODS: A Medline research was
      carried out looking for reports of pathoanatomical investigations of LVHT hearts.
      Excluded were reports in which a connection between the coronary arteries with
      the intertrabecular recesses were described. RESULTS: In 22 articles
      pathoanatomical findings of 37 hearts were described (9 women, 27 men, 1 not
      indicated). The age ranged from 26 gestational weeks to 80 years. Twenty-four
      hearts were investigated by autopsy, 13 as explanted hearts. The left ventricle
      was dilated in 29 patients. In 9 patients, a previous embolic event had occurred.
      All 9 patients had additional risk factors for embolism such as atrial
      fibrillation (n = 1), left ventricular dysfunction (n = 5) or atrial fibrillation
      and left ventricular dysfunction (n = 3). In only 2 patients, a thrombus was
      detected pathoanatomically. CONCLUSIONS: Thrombus-formation is a rare event in
      patients with LVHT. From these data we infer that LVHT in itself is no indication
      for oral anticoagulation. However, if additional cardiac abnormalities, known to
      increase the risk of embolism, like atrial fibrillation or left ventricular
      systolic dysfunction, accompany LVHT, they have to be treated as usual.

PMID- 15255469
TI  - Troponin I in atrial fibrillation with no coronary atherosclerosis.
AB  - A number of reports have raised the possibility that myocardial strain could be
      associated to increased plasma levels of troponin I. A 69-year-old, male,
      Caucasian, patient was admitted with prolonged chest pain and dyspnoea. The
      electrocardiogram showed atrial fibrillation with a ventricular rate of about 120
      to 150/minute. After treatment with digoxin and amiodarone, the patient returned
      to sinus rhythm. An elevation in the plasma levels of troponin I was noted, with
      a maximum value of 0.66 ng/ml. Coronary angiography showed absence of coronary
      artery atherosclerotic lesions. Atrial fibrillation of recent onset and with a
      relatively high heart rate may be yet another situation in which acute myocardial
      strain could be the cause of the abnormal release of cardiac troponin I.

PMID- 15255470
TI  - Diffuse intra-alveolar haemorrhage as a complication of thrombolytic therapy in
      acute myocardial infarction.
AB  - Diffuse intra-alveolar haemorrhage is a rare complication of thrombolytic therapy
      (TT). We report a patient who developed haemoptysis due to pulmonary haemorrhage.
      This diagnosis should be considered in any patients with respiratory distress,
      diffuse pulmonary infiltrates, and haemoptysis and otherwise unexplained decrease
      in haemoglobin concentration after thrombolytic therapy.

PMID- 15255471
TI  - Self-nonself discrimination by T lymphocytes.
AB  - Tolerance of T lymphocytes to self-antigens is mainly achieved at the level of
      the primary lymphoid organ, the thymus, and probably to a lesser extent in the
      secondary lymphoid tissues. Whether self-reactive lymphocytes ignore their target
      autoantigen, or are tolerized by the various mechanisms discussed, depends on the
      circumstances.

PMID- 15255472
TI  - On proteins, grids, correlations, and docking.
AB  - The activity of a living cell can be portrayed as a network of interactions
      involving proteins and nucleic acids that transfer biological information.
      Intervention in cellular processes requires thorough understanding of the
      interactions between the molecules, which can be provided by docking techniques.
      Docking methods attempt to predict the structures of complexes given the
      structures of the component molecules. We focus hereby on protein-protein docking
      procedures that employ grid representations of the molecules, and use correlation
      for searching the solution space and evaluating putative complexes. Geometric
      surface complementarity is the dominant descriptor in docking. Inclusion of
      electrostatics often improves the results of geometric docking for soluble
      proteins, whereas hydrophobic complementarity is more important in construction
      of oligomers. Using binding-site information in the scan or as a filter helps to
      identify and up-rank nearly correct solutions.

PMID- 15255473
TI  - How can we understand the construction of an organism?
AB  - Since a dozen years, biology is in a state of permanent technical and conceptual
      excitement. The pendulum is swinging back from the selectionist populationist
      biology of Darwin--the organism is a black box: viewed from the outside--to the
      mechanistic embryology of Aristotle--viewed from the inside of the organism-
      leading to a new interpretation of old concepts. This short text tries to get to
      the meaning of these events by putting them in historical and epistemological
      perspectives, through such concepts as teleology and differentiation, on the way
      describing several paradoxes: experimental results yield a detailed description
      of purposeless mechanical devices, explaining Nature, which, to us, appears
      purposeful.

PMID- 15255474
TI  - Analysis of fragments induced by simulated lattice protein folding.
AB  - The folding process of a set of 42 proteins, representative of the various folds,
      has been simulated by means of a Monte Carlo method on a discrete lattice, using
      two different potentials of mean force. Multiple compact fragments of contiguous
      residues are formed in the simulation, stable in composition, but not in
      geometry. During time, the number of fragments decreases until one final compact
      globular state is reached. We focused on the early steps of the folding in order
      to evidence the maximum number of fragments, provided they are sufficiently
      stable in sequence. A correlation has been established between these proto
      fragments and regular secondary-structure elements, whatever their nature, alpha
      helices or beta strands. Quantitatively, this is revealed by an overall mean one
      residue quality factor of nearly 60%, which is better for proteins mainly
      composed of alpha helices. The correspondence between the number of fragments and
      the number of secondary-structure elements is of 77% and the regions separating
      successive fragments are mainly located in loops. Besides, hydrophobic clusters
      deduced from HCA correspond to fragments with an equivalent accuracy. These
      results suggest that folding pathways do not contain structurally static
      intermediate. However, since the beginning of folding, most residues that will
      later form one given secondary structure are kept close in space by being
      involved in the same fragment. This aggregation may be a way to accelerate the
      formation of the native state and enforces the key role played by hydrophobic
      residues in the formation of the fragments, thus in the folding process itself.

PMID- 15255475
TI  - Performance of phaseolus bean rhizobia in soils from the major production sites
      in the Nile Delta.
AB  - The symbiotic and competitive performances of two highly effective rhizobia
      nodulating French bean P. vulgaris were studied in silty loam and clayey soils.
      The experiments were carried out to address the performance of two rhizobia
      strains (CE3 and Ph. 163] and the mixture thereof with the two major cultivated
      bean cultivars in two soil types from major growing French bean areas in Egypt.
      Clay and silty loam soils from Menoufia and Ismailia respectively were planted
      with Bronco and Giza 6 phaseolus bean cultivars. The data obtained from this
      study indicated that rhizobial inoculation of Giza 6 cultivar in clayey soil
      showed a positive response to inoculation in terms of nodule numbers and dry
      weight. This response was also positive in dry matter and biomass accumulation by
      the plants. The inoculant of strain CE3 enhanced plant growth and N-uptake
      relative to Ph. 163. However, the mixed inoculant strains were not always as good
      as single strain inoculants. The competition for nodulation was assessed using
      two techniques namely fluorescent antibody testing (FA) and REP-PCR
      fingerprinting. The nodule occupancy by inoculant strain Ph. 163 in both soils
      occupied 30-40% and 38-50 of nodules of cultivar Bronco. The mixed inocula
      resulted in higher proportions of nodules containing CE3 in silty loam soil and
      Ph. 163 in clayey soil. The native rhizobia occupied at least 50% of the nodules
      on the Bronco cultivar. For cultivar Giza 6, the native rhizobia were more
      competitive with the inoculant strains. Therefore, we suggest using the studied
      strains as commercial inocula for phaseolus bean.

PMID- 15255476
TI  - Genetic and molecular basis of grass cell-wall degradability. I. Lignin-cell wall
      matrix interactions.
AB  - Lignification limits grass cell-wall digestion by herbivores. Lignification is
      spatially and temporally regulated, and lignin characteristics differ between
      cell walls, plant tissues, and plant parts. Grass lignins are anchored within
      walls by ferulate and diferulate cross-links, p-coumarate cyclodimers, and
      possibly benzyl ester and ether cross-links. Cell-wall degradability is regulated
      by lignin concentration, cross-linking, and hydrophobicity but not directly by
      most variations in lignin composition or structure. Genetic manipulation of
      lignification can improve grass cell-wall degradability, but the degree of
      success will depend on genetic background, plant modification techniques
      employed, and analytical methods used to characterize cell walls.

PMID- 15255477
TI  - Genetic and molecular basis of grass cell-wall biosynthesis and degradability.
      III. Towards a forage grass ideotype.
AB  - Lignification of cell walls is the major factor controlling the digestibility of
      forage grasses. Thus far, from QTL analysis, about 15 locations involved in cell
      wall lignification or digestibility have been identified in the maize genome,
      many of which colocalise with QTLs involved in corn borer susceptibility. Genetic
      diversity for enhancing cell-wall digestibility in maize must be identified in
      novel germplasm, but genetic engineering is also a relevant way both to design
      specific cell-wall characteristics for improved digestibility and to identify
      genes involved in these traits for further discovery of alleles of interest in
      grass germplasm.

PMID- 15255478
TI  - [Critical analysis of the immunological self/non-self model and of its implicit
      metaphysical foundations].
AB  - An examination of the concepts used in immunology prompts us to wonder about the
      origins and the legitimacy of the notions of self and non-self, which constitute
      the core of the dominant theoretical model in this science. All theoretical
      reflection concerning immunology must aim at determining a criterion of
      immunogenicity, that is, an operational definition of the conditions in which an
      immune reaction occurs or does not occur. By criticizing both conceptually and
      experimentally the self/non-self vocabulary, we can demonstrate the inaccuracy
      and even the inadequacy of the dichotomy of self/non-self. Accordingly, the
      self/non-self model must be reexamined, or even rejected. On the basis of this
      critique, we can suggest an alternative theoretical hypothesis for immunology,
      based on the notion of continuity. The 'continuity hypothesis' developed here
      attempts to give a criterion of immunogenicity that avoids the reproaches leveled
      at the self model.

PMID- 15255479
TI  - Space utilization by a cormorant (Phalacrocorax carbo L.) colony in a multi
      wetland complex in relation to feeding strategies.
AB  - In this study, we investigated the response of inland breeding cormorants
      Phalacrocorax carbo to a complex spatial configuration of feeding habitats in
      relation to social and individual feeding strategies. The numbers of feeding
      trips outside the colony site (Lake Grand-Lieu, western France), where only
      solitary fishing is used by cormorants, and the number of birds fishing on the
      lake where social fishing predominates were investigated during the breeding
      season and compared with the fledging period. From the investigation of feeding
      trip traffic, we identified three major habitats used by cormorants in the
      vicinity of the colony site (< 25 km around the colony site) that accounted for
      94.1 of the IN flights and 92.0% of the OUT flights (n = 1745 arrivals and 2404
      departures respectively), and notably one area that accounted for 58% of total
      flights although it is the furthest away. No fundamental change in the relative
      significance of these feeding grounds for solitary fishing cormorants was found
      throughout the breeding season, even in a between-years comparison (1996-2001),
      in contrast to what has often been found elsewhere. Although the peak of foraging
      activity in the surrounding habitats and also within the lake waters largely
      coincided with the time when the majority of young had fledged, the index of
      cormorant numbers (ratio between bird numbers at a given time and that for a
      baseline date) on the lake remained at a high level until late August compared to
      movements outside the lake, as a result of regular social fishing (84.9 +/- 4.0%
      of fishing numbers). From these findings, we discuss factors governing the
      selection of feeding grounds throughout the breeding season in relation to energy
      considerations, feeding strategies and food resources.

PMID- 15255480
TI  - [A new species of wild mice on the Island of Cyprus].
AB  - A mitochondrial and nuclear gene analysis allowed us to precise the taxonomical
      position of the two sympatric species of mice known to be present on Cyprus. One
      of them is the commensal house mouse M. m. domesticus, and the other revealed to
      be a new taxon that is a sister species of M. spicilegus and M. macedonicus. The
      new species is equidistant from each of these, the divergence dating around 0.5-1
      Myr. Its origin either results from an ancient accidental colonisation of the
      island or from a recent transportation by the first epipalaeolithic settlers. In
      this last eventuality, the new species would also exist somewhere else in Asia
      Minor.

PMID- 15255482
TI  - Is there a future for primary care research?

PMID- 15255481
TI  - Sugary food robbing in ants: a case of temporal cleptobiosis.
AB  - This study reports new information on interactions between Ectatomma tuberculatum
      (Ponerinae) and Crematogaster limata parabiotica (Myrmicinae). Workers of these
      sympatric arboreal ant species forage on the same pioneer trees. Diurnally,
      Ectatomma preyed on Crematogaster workers that avoided overt aggression by
      respecting a 'safe distance'. At night, Crematogaster initiated raids within the
      Ectatomma nests that they apparently left with their abdomen empty, then remained
      near the nest entrances where they successfully intercepted 75.2% of the
      returning Ectatomma foragers (N = 322). Certain intercepted workers rapidly
      resumed their return trip. Others (39.1%) were stopped, explored and licked
      during a long time by the Crematogaster. Most of them were carrying between their
      mandibles a droplet of liquid food that was stolen. This relationship, that
      appears to be a typical case of interspecific cleptobiosis, whose expression
      varies during the daytime, demonstrates for the first time sugary-food robbing,
      instead of prey robbing, in ants.

PMID- 15255483
TI  - Diabetes care today: not everyone should have intensive multipharmacological
      treatment.
AB  - The uncritical promotion of intensive multipharmacological treatment for type 2
      diabetic patients is an example of simplistic communication of research results.
      The effect, practicability and safety of pharmacological treatment is greater for
      high than for low levels of blood glucose and other risk factors. The large
      number of poorly controlled diabetic patients is a further argument for
      concentrating the treatment effort on those patients at highest risk. A pragmatic
      risk balance sheet can be used to decide when to start treatment even at
      relatively low levels of risk factors. We need such a framework in which we can
      individualise goal-setting and treatment.

PMID- 15255484
TI  - Individualised treatment goals in diabetes care.
AB  - OBJECTIVES: To examine 1) patients' characteristics according to the treatment
      goal chosen at diabetes diagnosis, and 2) the association between individualised
      goals for glycated haemoglobin (HbA1c), blood pressure (BP) and lipids, and the
      risk factor level subsequently achieved. DESIGN: Follow-up study embedded in a
      multifaceted intervention study directed at doctors encouraging individualised
      goal-setting in newly diagnosed diabetic patients aged > or = 40 years. SETTING:
      General practice. SUBJECTS: In all, 243 general practitioners and 674 patients
      participated. MAIN OUTCOME MEASURES: Risk factors for diabetic complications.
      RESULTS: Relatively young age, low diagnostic plasma glucose, low BMI, a moderate
      or high level of physical activity and normoalbuminuria were associated with a
      treatment goal of good control at diagnosis. After 5 years, median HbA1c was
      8.2%, 8.6% and 8.0% in patients with a goal of good, acceptable and poor control,
      respectively. Patients with a goal of good control versus those with a goal of
      acceptable control had a lower HbA1c level in a regression analysis adjusted for
      age, sex, HbA1c at diagnosis, BMI, total cholesterol, fasting triglycerides, BP,
      physical activity, smoking status and diabetes duration. We found no association
      between goals and the level of BP and lipids. CONCLUSION: Doctors tend to pursue
      normoglycaemia in relatively young patients with low blood glucose, low BMI, high
      activity level and normoalbuminuria. Patients for whom a goal of normoglycaemia
      was chosen at diagnosis achieved favourable glycaemic control at 5-year follow
      up. Whether doctors choosing the goals were good at predicting future glycaemic
      control, or whether goal-setting is an important motivational factor in achieving
      optimal glycaemic control needs to be explored.

PMID- 15255485
TI  - Screening for low bone mineral density with quantitative ultrasound within the
      primary health care system.
AB  - OBJECTIVE: To screen risk groups for low bone mineral density by quantitative
      ultrasound in primary health care. DESIGN: Cross-sectional. INTERVENTION: None.
      SUBJECTS: Risk categories for osteoporosis (a fragility fracture, malabsorption,
      immobilisation, inflammatory joint disease, glucocorticoid, fenantoin or thyroxin
      treatment, renal insufficiency or "miscellaneous"), 775 women and 179 men aged
      between 40 and 93 were measured. MAIN OUTCOME MEASURES: Calcaneus quantitative
      ultrasound stiffness index T-score below -2.5 standard deviation (SD). RESULTS:
      41% of women and 24% of men and more than 80% of women and 50% of men over the
      age of 80, within the risk groups, had a stiffness index T-score below -2.5 SD.
      All over 80 years with a fragility fracture had a stiffness index T-score below 
      2.5 SD. Men aged 50-59 within the risk groups had lower stiffness index T-scores
      than controls (-1.4 versus -0.6, p = 0.05). Individuals with a fragility fracture
      had lower stiffness index T-scores than controls, women aged 70-79 years (-3.1
      versus -2.4, p < 0.05) and men aged 60-69 years (-2.3 versus -1.2, p < 0.05).
      CONCLUSION: Quantitative ultrasound calcaneus used in gender-specific, diagnosis
      specific and age-specific cohorts can capture individuals with low bone mass.

PMID- 15255486
TI  - Sputum specimens can be obtained from patients with community-acquired pneumonia
      in primary care.
AB  - OBJECTIVE: To improve the aetiological diagnosis in community-acquired pneumonia
      (CAP) increased efforts were made to obtain expectorated sputum specimens from
      patients with CAP. DESIGN: A prospective, clinical study. Patients were
      encouraged to cough spontaneously and to expectorate a sputum specimen. If
      unsuccessful, they were asked to inhale nebulized hypertonic saline to induce
      secretion and cough. SETTING: One primary health care centre in Orebro, Sweden.
      SUBJECTS: Patients attending the Health Centre with acute symptoms of CAP. MAIN
      OUTCOME MEASURES: Availability and quality of sputum specimen from patients with
      CAP in primary care. RESULTS: 177 patients were included, 63% were women and the
      mean age was 51 years. 28% were smokers and 46% showed infiltrates on chest X
      ray. Sputum specimens were obtained from 125 patients. Fifty-nine were
      expectorated spontaneously and 66 were induced. Ninety-one of the specimens were
      found to be acceptable, whereas 34 were discarded. Potential pathogens were found
      in 57% of the 91 specimens. CONCLUSION: Acceptable sputum specimens can be
      obtained with some effort from approximately half of the patients in primary
      care. Sputum culture might improve the knowledge of the bacterial aetiology of
      CAP in selected patients and in epidemiological studies.

PMID- 15255487
TI  - Preparedness for cardiopulmonary resuscitation in primary care.
AB  - OBJECTIVE: To evaluate preparedness for resuscitation of patients in cardiac
      arrest in primary care. DESIGN: Questionnaire study sent to every health centre
      in Finland (n = 277). SETTING: Primary care. MAIN OUTCOME MEASURES: Resuscitation
      training frequency and prevalence of automated external defibrillators and nurse
      performed early defibrillation. RESULTS: One-hundred-and-forty-one health centres
      (51%) responded to the survey. Fifty-nine percent had appointed one person to be
      in charge of resuscitation training. The nurses in these health centres were
      trained to defibrillate (p < 0.001), physicians had advanced life support
      training (p < 0.001) and the first defibrillation was likely to be performed by a
      nurse on the ward (p < 0.01) more often. In 87% of health centres, it was not
      customary to defibrillate before the physician arrived beside the patient. Forty
      four percent of the health centres used only manual defibrillators, 26% used
      automated external defibrillators and 30% used both. Only 18% of respondents
      considered resuscitation training in their health centre to be sufficient and
      systematic. CONCLUSION: Resuscitation training appears insufficient and non
      systematic in most health centres in Finland. Automated external defibrillators
      are not in common use. In health centres with an appointed person in charge of
      resuscitation training, the training is more often regular.

PMID- 15255488
TI  - Is frequent attendance a persistent characteristic of a patient? Repeat studies
      of attendance pattern at the family practitioner.
AB  - OBJECTIVE: To assess the extent of frequent attendance as a persistent
      characteristic of patients by repeat studies of attendance at a health centre.
      DESIGN: A follow-up of frequent attenders and compared patients in 1991 among
      frequent attenders in 1996. SETTING: Mariehem health centre in Umea in northern
      Sweden providing care for 10,500 and 12,000 inhabitants in 1991 and 1996,
      respectively. SUBJECTS: Frequent attenders, defined as patients who had at least
      5 consultations with physicians during 1 year at the health centre, compared to
      attenders who had between 1 and 4 consultations in 1991 and 1996. RESULTS: The
      proportion of people who lived in the area and consulted a doctor at the health
      centre at least once during 1 year increased from 40.0% in 1991 to 45.2% in 1996.
      The number of frequent attenders increased from 179 to 303 and they took 15% and
      20% of all consultations in 1991 and 1996, respectively. Twenty-five patients (21
      females and 4 males) were identified as frequent attenders in both years.
      CONCLUSION: With the exception of a small group of patients, mostly females,
      frequent attendance seems not to be a persistent characteristic of patients.

PMID- 15255489
TI  - Health care utilisation before and after retirement due to illness. A 13-year
      population-based follow-up study of prematurely retired men and referents from
      the general population.
AB  - OBJECTIVE: To test the hypothesis that prematurely retired men have long-term
      unspecifically increased health care utilisation, indicating broader health
      deterioration than reflected by the retirement diagnosis. DESIGN: A two-cohort
      study. SETTING: The City of Eskilstuna, Sweden. SUBJECTS: 215 men aged 30-54
      years who retired early due to illness and a random sample of 620 referents of
      the same age from the general population. MAIN OUTCOME MEASURES: Health care
      utilisation from 5 years before retirement until 13 years after retirement.
      RESULTS: The retired men had 7.2 times higher utilisation of primary health care
      during the baseline year and 2-3 times higher rates of hospital admissions than
      the referents during the 13-year follow-up. The panorama of main hospital
      discharge diagnoses was the same among retired men and referents irrespective of
      the retirement diagnoses of the former. Over time, health care utilisation among
      the retired men decreased, but was constant among the referents. After 13 years,
      the retired men still had twice the rate of the referents. CONCLUSION:
      Prematurely retired men had high health care utilisation also after retirement.
      They appear to have broader health deterioration than reflected by the retirement
      diagnosis.

PMID- 15255490
TI  - Generation shift in family vs. working conditions as most important influence on
      women's mood? The Prospective Population Study of Women in Gothenburg, Sweden.
AB  - OBJECTIVE: To find out whether family or working conditions is most important for
      mood in different ages in women. DESIGN: Prospective study. SETTING: Goteborg,
      Sweden, population about 430,000. SUBJECTS: Representative samples of a general
      population of women, born in 1930 (n = 276), 1942 (n = 93) and 1954 (n = 61),
      examined both in 1980-81 and 1992-93. MAIN OUTCOME MEASURES: Associations between
      "mood" and different social factors indicated by correlation coefficients and
      studied cross-sectionally and longitudinally. RESULTS: In younger women, the
      variable "mood" was associated with variable work situation but not family
      situation (correlation coefficient 0.47, p <0.001, and correlation coefficient
      0.26, not statistically significant, respectively), while in older women "mood"
      was associated with variable family situation as well as work situation
      (correlation coefficients 0.45 and 0.41, p <0.01 both). Changes in the mood
      variable between 1980-81 and 1992-93 were associated with changes in working
      conditions in the younger cohort, but with changes in variable family conditions
      in the older cohort. CONCLUSIONS: In the latest born cohort, the importance of
      women's paid work outside the home was increased as an influential factor on mood
      in comparison with the importance of the family situation, while the situation
      was the opposite in the earlier born cohorts.

PMID- 15255491
TI  - Structured home visits to older people. Are they only of benefit for women? A
      randomised controlled trial.
AB  - OBJECTIVE: To investigate whether education of primary care professionals
      improved functional ability in home-dwelling older people, with special focus on
      gender differences. DESIGN: A prospective controlled three-year follow-up study
      (1999-2001) with randomisation and intervention at municipality level and
      outcomes measured at individual level. Intervention municipality visitors
      received regular education and GPs were introduced to a short assessment
      programme. Control municipalities received no education but conducted the
      preventive programme in their own way. SETTING: Primary care, 34 municipalities.
      SUBJECTS: 5788 home-dwelling 75- and 80-year-olds were invited. 4060 (70.1%)
      participated: 2104 in 17 intervention- and 1956 in 17 matched control
      municipalities. The main outcome measure was obtained from 3383 (95.6%) of 3540
      surviving participants. MAIN OUTCOME MEASURE: Functional ability. RESULTS:
      Municipality intervention in coordination with GPs was associated with better
      functional ability in women (OR: 1.26; CI95: 1.08-1.47, p=0.004), but not in men
      (OR: 1.04; CI95: 1.85-1.27). Accepting and receiving free preventive home visits
      was associated with better functional ability among women (OR: 1.36; CI95: 1.16
      1.60, p=0.0002), but not among men (OR: 0.98; CI95: 0.80-1.21). CONCLUSION: A
      brief, feasible educational intervention for primary care professionals and to
      accept and receive preventive home visits may have effect in older women, but not
      in older men.

PMID- 15255492
TI  - Changes in urinary incontinence and quality of life after four years. A
      population-based study of women aged 22-50 years.
AB  - OBJECTIVES: To investigate (a) the incidence and remission rates of female
      urinary incontinence (UI), (b) changes in type of UI and quality of life (QoL),
      and (c) whether professional help had been consulted regarding UI. DESIGN: A 4
      year follow-up population-based cohort study. SETTING: Surahammar, Sweden, a
      community of 10,500 inhabitants. SUBJECTS: All 118 incontinent and 130 continent
      women aged between 22 and 50 years. MAIN OUTCOME MEASURES: Changes in type of UI
      were measured using the Detrusor Instability Score (DIS), which was used to
      distinguish between the stress incontinent and the urge incontinent women.
      Changes in QoL were measured using the SF-36 Health Survey. RESULTS: The mean
      annual incidence and remission rates of UI were the same (4%). The majority of
      women (83%) reported unchanged UI after 4 years and 77% of these women had stress
      incontinence. At follow-up, the changes in QoL scores were significantly greater
      in five out of eight dimensions in the persistently incontinent group compared
      with the persistently continent group. QoL scores did not change significantly
      from baseline to the 4-year follow-up within the incidence and remission groups.
      Three of four women with UI had not sought professional help. CONCLUSIONS: At 4
      year follow-up the type of UI is fairly stable in women below 50 years of age.
      The QoL decreases in five dimensions, but the clinical relevance of this might be
      questioned. Most women with UI had not sought professional help.

PMID- 15255493
TI  - Women's needs and wants when seeing the GP in relation to menopausal issues.
AB  - OBJECTIVE: To explore women's needs and wants when seeing the GP in relation to
      menopausal issues. DESIGN: A qualitative interview study. SETTING AND SUBJECTS:
      The study was part of a larger project, targeting menopause. It included in-depth
      interviews of 24 women aged 52-53 years who came from all over Denmark. The women
      showed a great variety of menopausal experience of symptoms and treatment. MAIN
      OUTCOME MEASURES: An acquaintance with the women's agendas when seeing the GP
      about menopausal issues. RESULTS AND CONCLUSION: Women consulting their GPs
      either wanted to discuss treatment for menopausal symptoms, to have an
      examination for diseases or to get a risk assessment. Their needs for medication
      or examination were satisfied but several women wanted more information,
      especially about the pros and cons of hormone therapy (HT). Risk assessment, if
      not requested, indicated problems, with some women feeling uncomfortable if the
      GPs started a discussion about HT and osteoporosis, if they only wanted an
      examination to be reassured that everything was normal. The authors' findings
      indicate that GPs encounter a subtle balance in considering the question of risk
      information to menopausal women who do not request it.

PMID- 15255494
TI  - Management of acute maxillary sinusitis in Finnish primary care. Results from the
      nationwide MIKSTRA study.
AB  - OBJECTIVES: To study the management of acute maxillary sinusitis (AMS) in Finnish
      primary care and to compare it both to recommendations in national guidelines and
      to the management of other upper respiratory tract infections (URTI). DESIGN: A
      cross-sectional multi-centre epidemiological survey. SETTING: Thirty primary care
      health centres in Finland. SUBJECTS: 7284 patients with symptoms of possible
      acute rhinosinusitis during one week in both November 1998 and November 1999.
      MAIN OUTCOME MEASURE: Symptoms and their duration, use of diagnostic tools,
      choice of antibiotics, patient outcomes. RESULTS: A total of 1601 patients were
      diagnosed as having AMS (12% of all patients with infectious disease). In 45% of
      cases the differentiation between AMS and URTI was based on clinical examination
      alone. Sinus ultrasound was the most common diagnostic tool used (38%). Sinus
      radiography or blood tests (CRP or leukocytes) were both studied in 8% of cases.
      AMS was diagnosed and treated with antibiotics also in the early stages of URTI
      when viruses are the most likely explanation. In total, 83% of patients with AMS
      received a prescription for antibiotics; the most common choice was amoxycillin
      (37%), doxycycline was used in 29% of cases, and macrolides in 15%. CONCLUSIONS:
      Antibiotics are prescribed for AMS 2 to 5 times more often than true disease
      incidence would suggest in Finland. The choice of antibiotics follows the
      guideline recommendations; however, use of macrolides is higher than recommended.
      Physicians feel strong pressure from patients to prescribe antibiotics for AMS.
      Primary care physicians need better support in the accurate diagnosis of AMS.

PMID- 15255495
TI  - Late responders and bias in questionnaire studies.

PMID- 15255496
TI  - Notes from a small island.

PMID- 15255497
TI  - Job strain, effort--reward imbalance, and stress at work: competing or
      complementary models?
AB  - BACKGROUND: The Demand Control Model (DCM) and the Effort Reward Imbalance Model
      (ERI) offer putative explanations of the relationship between stressful working
      conditions, job strain, and psychological and physical ill health. AIMS: The aims
      of this study are to: (a) compare the predictive powers of the two models for
      explaining perceived job stress and mental distress amongst workers as a whole,
      (b) identify whether a model which combines dimensions of the DCM and ERI might
      have more predictive power than either of them separately, and (c) ascertain
      whether the models make distinct contributions to explaining stress at work in
      specific occupational settings. METHODS: Statistical analysis was carried out on
      data collected from a cross-sectional postal survey of a random sample (n =
      7,069), of the adult population in an urban area in Southern England. The
      analysis focused on the 4,135 respondents who were in paid employment. RESULTS:
      There was little support for combining the models as the combined model was
      dominated by the predictive power of dimensions from the ERI. However, the
      results also showed that the models or dimensions of the models made distinct
      contributions to explaining perceived work stress in different types of
      occupation. CONCLUSIONS: There is little evidence to support a combined model of
      work characteristics. The ERI appears to be the stronger of the two models
      although the DCM has explanatory value for specific occupations.

PMID- 15255498
TI  - Sickness absence due to musculoskeletal diagnoses: association with occupational
      gender segregation.
AB  - BACKGROUND: Musculoskeletal disorders represent a considerable public health
      problem and the most common diagnoses behind sickness absence and disability
      pensions. However, little is known about how sickness absence with these
      diagnoses varies with the strong gender segregation of the labour market. AIMS: A
      study was undertaken to investigate the association between musculoskeletal
      related sickness absence and occupational gender segregation. METHODS: The study
      was population based, and included all new sick-leave spells exceeding seven days
      due to musculoskeletal diagnoses, comprising neckl shoulder pain, low back pain,
      and osteoarthritis in Ostergotland county, Sweden, which has 393,000 inhabitants
      (5%, of the national population). The participants were all sick-leave insured
      employed persons in Ostergotland (n = 182,663) in 1985. RESULTS: Cumulative
      incidence of musculoskeletal-related sickness absence (>7 days) was higher for
      women (7.5%, 95% confidence interval [C.I.] 7.3-7.7) than for men, (5.8%, C.I.
      5.6-5.9), and the same was true for the mean number of sick-leave days (women 81,
      C.I. 78-83; men 65, C.I. 63-68). Grouping occupations according to degree of
      numerical gender segregation revealed the highest incidence and duration of
      sickness absence for women in male-dominated occupations. For both genders, the
      lowest cumulative incidence and duration occurred in gender-integrated
      occupations. CONCLUSIONS: Our results indicate a strong association between
      occupational gender segregation and musculoskeletal-related sickness absence.
      Further studies are needed to elucidate gender segregation of the labour market
      in relation to health and rehabilitation measures.

PMID- 15255499
TI  - Voluntary HIV testing in Europe.
AB  - AIMS: A study was undertaken to examine patterns of voluntary HIV testing among
      heterosexuals across Europe. METHODS: Cross-sectional surveys on sexual behaviour
      and HIV were performed including probability samples of the general population
      ages 18-49 years in Greece (n = 2,000), Italy (n = 2,603), Switzerland (n =
      2,777), and Norway (n = 3,704). RESULTS: Prevalence of lifetime voluntary HIV
      testing among heterosexuals is 10.1%, 15.5%, 17.4%, and 40.9%, in Greece, Italy,
      Norway, and Switzerland, respectively. Between 49.0%, and 89.3% of individuals
      reporting risk behaviours never sought voluntary testing. Multivariate analysis
      shows that in some countries the likelihood of HIV testing is significantly
      higher for individuals aged 24-29 and 30-39 years, compared with younger
      respondents with the same risky behaviour. Among Swiss men and women higher
      educational level also significantly increases the probability of testing.
      CONCLUSIONS: The prevalence of voluntary HIV testing among heterosexuals with
      histories of risk is low. The needs of specific groups should be considered to
      improve HIV prevention and access to care.

PMID- 15255500
TI  - Long-term sick leave and its risk factors during pregnancy among Danish hospital
      employees.
AB  - AIM: The authors sought to describe risk indicators of long-term sick leave
      during pregnancy among hospital employees. METHODS: A register-based study was
      undertaken of 4,852 female hospital employees aged 20-45 years from the second
      largest hospital in Denmark during 1995-99 based on job titles, working time,
      sick leave, and births combined with a survey among a total of 773 women who had
      been pregnant during their employment (response rate 85%). RESULTS: Altogether
      236 (31%) were on sick leave for at least 10% of their scheduled work time during
      their latest pregnancy and 169 (22%) had been absent at least 20% of the time.
      The pregnant women had an average sickness absence of 6.1 days per month, non
      pregnant women 0.95 days per month. Sick leave was more frequent in late than in
      early gestation. Women employed as nursing aides or hospital orderlies,
      launderers, and nurses had more sick leave days than other hospital employees.
      Part-time work, previous sickness absence not related to pregnancy, and previous
      chronic back pain were risk factors for long-term sick leave as were much walking
      or standing, long working days, high work level, little practical support from
      supervisors and colleagues, low job control, much lifting and night or shift
      work. Sick leave was unrelated to family size, support from the family and number
      of working years. CONCLUSION: Long-term sick leave during pregnancy was frequent
      and to some extent predictable. Efforts should be made to organize work for
      pregnant women in a manner that optimizes their health and well-being.

PMID- 15255501
TI  - Predictors of smoking behaviour among indigenous sami adolescents and non
      indigenous peers in north Norway.
AB  - AIMS: A study was undertaken to examine predictors of smoking behaviour among
      indigenous Sami adolescents and non-indigenous peers in North Norway, and to
      examine for ethnic-specific predictors. METHODS: This is a cross-sectional and
      longitudinal school-based and postal questionnaire study initially including
      2,718 10th to 12th grade students (response rate (RR): 85%) in 1994-95 (T1). At
      the three-year follow-up (T2), in 1997-98, 1,405 were included (RR: 57%).
      Indigenous Sami contributed 23% (599/324) of the total samples. Logistic
      regression was used to examine the influence of sociodemographic and psychosocial
      predictors on smoking behaviour. RESULTS: The proportions of regular smokers were
      33% (729) and 35% (401) at T1 and T2, respectively, while 19% (153) had initiated
      current smoking during the study period. Substance use, externalizing problems,
      sexual activity and vocational training (p </= 0.01) predicted regular smoking
      both cross-sectionally and prospectively. Among non-smokers at T1, age and
      frequent alcohol intoxication predicted current smoking prospectively (p </=
      0.01). Frequent intoxication predicted all stages of smoking (p </= 0.001).
      Ethnicity did not predict smoking in this study. Laestadian Christian affiliation
      increased the prevalence of experimental smoking at T1 but only for Sami
      students. CONCLUSIONS: Youth smoking behaviour was strongly associated with risk
      taking behaviours, indicating that a broader focus on health-compromising
      behaviours in anti-smoking campaigns is needed. The findings indicate little need
      for culturally sensitive anti-smoking campaigns specially designed for indigenous
      Sami youth, as the main predictors (risk-taking behaviours) were similar across
      ethnic groups.

PMID- 15255502
TI  - Adverse events due to change in organization of problem drug users' treatment?
AB  - AIMS: This study set out to identify any undesirable consequences of legislative
      change in the organization of the treatment of problem drug users (PDUs), which
      aimed to combine their social and medical care. METHOD: The method used was a
      register-based three-year follow-up prevalent cohort study. RESULTS: On 1 January
      1996, the law was changed to allocate unambiguous and undivided responsibility
      for the combined social and medical care of PDUs in Denmark. The main objective
      of the legislative change was to move PDUs from treatment by general
      practitioners (GPs) and at private clinics to treatment institutions under the
      control of the counties. The possibility remained that medical treatment could,
      however, continue to be given by GPs or private clinics, based on specific
      agreements. The study showed that at the end of the period, 31 December 1998, two
      thirds remained in treatment at private clinics or at GP surgeries. During the
      period only 8% of users were at some time without methadone treatment; 2%
      remained without methadone treatment throughout the study period. CONCLUSION: The
      transition from GPs and private clinics to the county treatment centres went
      smoothly. The number of PDUs in MMT (methadone maintenance treatment) in the city
      of Copenhagen increased in the period 1995 to 1998. The average quantity of
      methadone given to the cohort increased during these years from 72 mg per day to
      92 mg per day. The legislative change therefore did not result in a higher
      threshold for treatment or a more restrictive prescription of methadone. No
      adverse effect on crime, hospital admissions, or death could be attributed to the
      legislative change in treatment organization.

PMID- 15255503
TI  - The validity of self-reported fractures among Danish female nurses: comparison
      with fractures registered in the Danish National Hospital Register.
AB  - BACKGROUND: The authors compared self-reported non-spine fractures obtained from
      a cohort of Danish female nurses with fracture diagnoses registered in the Danish
      National Hospital Register (DNHR). METHOD: The self-reported fracture history was
      obtained from a questionnaire and was related to fracture information registered
      with the DNHR by means of the unique person identification code of Danish
      citizens. A total of 166 self-reported hip fractures, 391 self-reported wrist
      fractures, and 121 self-reported upper arm fractures were available for the
      comparison. The self-reported fractures were initially compared with the anatomic
      specific fracture diagnoses registered in the DNHR. Second, the comparison also
      included fracture diagnoses of adjacent skeletal sites (unspecific fracture
      diagnoses). RESULTS: The positive predictive value of a positive report of hip
      fracture was 89%. Inclusion of unspecific registered hip fractures increased the
      positive predictive value to 94%. The same figures for wrist fractures were 75%
      and 84%, respectively, and for upper arm fractures 54% and 83%, respectively. The
      predictive value of a negative report of hip fracture was 99.5%. The fracture
      year was correctly reported in 76% of the hip fracture cases, 81% of the wrist
      fracture cases, and 82% of the upper arm fracture cases. Predictors of false
      positive report of fractures were young age ( < 60 years), report of indoor falls
      in the previous year, and use of hormone replacement therapy (HRT). CONCLUSION:
      The authors conclude that self-report of hip, wrist, or upper arm fractures among
      Danish nurses is relatively accurate but varies by the site of fracture. False
      positive reports of fracture introduce only modest bias fracture risk estimates
      and tend to dilute the association between exposures and fracture.

PMID- 15255504
TI  - Male and female physicians show different patterns of gender bias: a paper-case
      study of management of irritable bowel syndrome.
AB  - AIMS: Research has raised concerns about gender bias in medicine, i.e. that men
      and women might be treated differently due to gender-stereotyped attitudes among
      physicians. The authors investigated gender differences in medical management of
      a common health problem, irritable bowel syndrome (IBS). METHOD: In a national
      examination for Swedish house officers, the examinees were allocated to suggest
      management of IBS in either a male or female paper-patient. The case description
      was identical in both genders with the exception of prior prostate and
      gynaecological symptoms. The open answers were coded for analysis. A total of 289
      physicians (45% women) participated. Chi-squared tests were used to measure
      differences in proportions. RESULTS: In variables focusing on medication, weight,
      gynaecological problems, tobacco, alcohol, thyroid function, proposed diagnoses,
      X-ray of the colon, and advice about lifestyle, significant or close to
      significant gender differences were seen. Both male and female physicians made
      gender differences but they did not show the same pattern of differences.
      CONCLUSIONS: The results suggest that gender bias is involved in medical
      management of IBS but men and women physicians may show disparate patterns of
      gender bias. There is a need for larger studies on gender differences in medical
      management with designs making it possible to consider the gender of both the
      patient and the physician. Furthermore, the results call attention to 'knowledge
      mediated gender bias', a phenomenon implying that once knowledge about gender
      differences in a condition has been established, this might in fact cause gender
      biased assessments of individual patients in clinical practice.

PMID- 15255505
TI  - The state of scientific publishing: problems and promise.

PMID- 15255506
TI  - Sneddon's syndrome: clinical and laboratory analysis of 10 cases.
AB  - Sneddon's syndrome is characterized by livedo reticularis and cerebrovascular
      lesions. We report the cases of women (mean age, 36.2 +/- 8.1 years) diagnosed
      with Sneddon's syndrome based on the presence of livedo reticularis and
      characteristic cerebrovascular findings. Seven of these patients had cerebral
      infarcts on cranial computed tomography scan. Antiphospholipid antibodies were
      positive in 6 of these cases. Three cases had abnormal levels of antithrombin
      III. Analyses of chromosome 6 revealed no abnormalities. In 3 of the cases,
      investigation of the pedigrees revealed autosomal dominant traits. Two cases had
      epilepsy, and 3 had migraine. One case with migraine also had myasthenia gravis.
      In addition, we detected inferior altudinal hemianopia in 2 cases, cognitive
      functional disorder in 3 and depression in 2. Based on these findings, the entire
      vascular, haematologic, neurologic, and dermatologic systems should be evaluated
      in patients diagnosed with Sneddon's syndrome.

PMID- 15255507
TI  - Induction and prevention of virus-associated malignant lymphoma by serial
      transmission of EBV-related virus from cynomolgus by blood transfusion in
      rabbits.
AB  - Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially
      transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood
      transfusion, which subsequently induced virus-associated rabbit lymphomas. The
      virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or
      irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was
      no transmission with transfusion of cell-free plasma (0/6) from the infected
      rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased
      during the first 1-2 weeks in the transfused rabbits. The virus-transmitted
      rabbits showed a gradual increase in antibody titers ranging from peak titers of
      x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant
      lymphoma that developed in the first rabbit transfused by infected blood was
      confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related
      herpesvirus is serially transmissible by blood transfusion and that transmission
      can not be completely prevented by irradiation of blood, but removal of blood
      cells is the best way to prevent transmission of EBV-related virus. Therefore,
      this animal model provides a convenient in vivo system for studies of the
      prevention and therapy of transfusion-related transmission of EBV and EBV
      associated lymphoproliferative diseases in immunocompromised human beings.

PMID- 15255508
TI  - Differentiation of thyroid nodules using Tl-201 scintigraphy quantitative
      analysis and fine-needle aspiration biopsy.
AB  - We studied the differentiation of thyroid nodules using fine-needle aspiration
      biopsy (FNA) and Tl-201 scintigraphy quantitative analysis. One-hundred and
      thirty-one thyroid nodules were examined: 83 follicular lesions (58 benign and 25
      malignant lesions) and 48 non-follicular lesions (8 benign and 40 malignant
      lesions). During Tl-201 scintigraphy examinations, an early and a delayed image
      were acquired 10 and 120 min after an intravenous injection, respectively. The
      T/N ratio (counts of nodular lesion/counts of contralateral normal thyroid
      tissue) of each image was calculated quantitatively. We assessed the ability of
      the Tl-201 scintigraphy and of the FNA analysis to differentiate benign and
      malignant lesions and determined the cut-off levels for the assays. For the
      follicular lesions, the area under the ROC (Receiver Operating Characteristic)
      curve (Az) for the Tl-201 scintigraphy data was greater than that for the FNA
      data. For the non-follicular lesions, the Az for the FNA data was greater than
      that for the Tl-201 scintigraphy data. We set cut-off levels at 1.370 for
      follicular lesions, and 1.070 for non-follicular lesions. The sensitivity and
      specificity were 76% and 82.7% for follicular lesions, and 90% and 87.5% for non
      follicular lesions, respectively. The overall accuracy of the analysis was 84.0%.

PMID- 15255509
TI  - Talonavicular joint abnormalities and walking ability of patients with rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is often associated with deformities of the feet, and
      foot pain often arises in the talonavicular joint of patients with RA. The object
      of this study was to assess the relationship between magnetic resonance imaging
      (MRI) findings of the talonavicular joint and walking ability. The subjects were
      35 RA patients (10 feet in 5 males and 56 feet in 30 females) aged 34-87 years
      (mean: 70 years +/- 12.1), with a disease duration from 1-54 years (mean: 14
      years +/- 12.1). MRI findings were classified as follows: Grade 1, almost normal;
      Grade 2, early articular destruction; Grade 3, moderate articular destruction;
      Grade 4, severe articular destruction; and Grade 5, bony ankylosis dislocation.
      Walking ability was classified into one of 9 categories ranging from normal gait
      to bedridden status according to the system of Fujibayashi. As the grade of MRI
      images became higher the walking ability decreased, and these parameters showed a
      correlation by Spearman's rank correlation coefficient analysis (P = 0.003).
      Thus, in the present cohort group of patients with RA, the deterioration of
      walking ability increased with the severity of destruction of the talonavicular
      joint.

PMID- 15255510
TI  - The close relationship between decreases in extracellular GABA concentrations and
      increases in the incidence of hyperbaric oxygen-induced electrical discharge.
AB  - To elucidate the mechanism by which hyperbaric oxygen (HBO2) induces electrical
      discharge, changes in the extracellular concentrations of GABA and glutamate were
      measured every 5 min using a microdialysis technique in rats during a period of
      exposure to HBO2 (5 atm abs). Electrical discharge was observed at 28 +/- 4 min
      after the onset of exposure. Though the extracellular concentrations of glutamate
      remained unchanged, the extracellular GABA concentrations (pre-exposure level,
      0.026 +/- 0.005 microM in dialysate) began to decrease 15 min after the onset of
      exposure and reached their lowest level (74 +/- 14%, 0.019 +/- 0.004 microM) at
      the time of appearance of the discharge. There was a close logistic relationship
      between extracellular GABA concentrations and the discharge incidence, and the
      extracellular concentrations of GABA causing electrical discharge in 50% of the
      animals were estimated to be 80% of the pre-exposure level. These results suggest
      a possible mechanism that HBO2 exposure-induced discharge is caused by the
      decrease in extracellular concentration of GABA.

PMID- 15255511
TI  - Hepatic infarction following abdominal interventional procedures.
AB  - To clarify the incidence, background, and progress of hepatic infarction
      following interventional procedures, cases of hepatic infarction following
      interventional procedures at our department during the last decade were
      identified by reviewing the clinical records of 1982 abdominal angiography and
      interventional procedures and records of abdominal CT. Nine episodes (0.5%) in 8
      patients were identified as hepatic infarction following an interventional
      procedure. Five episodes were preceded by embolization of the hepatic or celiac
      artery at emergency angiography for postoperative bleeding with hemorrhagic
      shock. Three episodes followed the elected interventional procedure for
      hepatocellular carcinoma, and the remaining episode occurred after 12 months of
      chemoinfusion through an indwelling catheter in the hepatic artery and portal
      vein. Hepatic arterial occlusion in all episodes and portal venous flow
      abnormality in 5 episodes were observed on angiography. Four patients whose liver
      function was initially impaired died of hepatic infarction, although the extent
      of the disease on CT did not appear to be related to the mortality. Multiple risk
      factors, including arterial insufficiency, were observed in each patient. The
      incidence of hepatic infarction following interventional procedures in this
      series was low but sometimes fatal, and occurred most frequently in emergency
      embolization in hemorrhagic shock.

PMID- 15255512
TI  - Catastrophic secondary antiphospholipid syndrome with peripheral nervous system
      involvement: a case report.
AB  - A 34-year-old woman was admitted to our emergency room with a high fever,
      abdominal pain, dyspnea and confusion. High fever and abdominal pain had first
      occured after a cystocele operation 5 months earlier. Later, congestive heart
      failure with mural thrombus formation, peripheral polyneuropathy and ischemic
      cerebrovascular accident were identified in clinical follow-ups, and multiple
      arterial and venous thromboses were seen on cranial and abdominal magnetic
      resonance imaging angiography. The patient's symptoms improved with anticoagulant
      treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG
      levels was diagnosed, and ischemic peripheral polyneuropathy with axonal
      degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome,
      elevated anticardiolipin antibodies appear to be the most common acquired blood
      protein defect causing thrombosis. Disseminated vascular thrombosis in
      catastrophic antiphospholipid syndrome can result in multiorgan failure with
      increased morbidity and mortality. It rarely occurs secondary to various
      infections as in the case of our patient, who suffered postoperative
      intraabdominal infection. It is important to note that peripheral nervous system
      involvement is rare in antiphospholipid syndrome.

PMID- 15255513
TI  - Chairman's editorial: Control Alt Delete.

PMID- 15255514
TI  - Personal digital assistants.
AB  - Personal digital assistant sales are growing exponentially, and as medical
      technology advances the amount of information available becomes staggering,
      making a handheld device, with the ability to store a great amount of
      information, progressively more valuable to health care providers. Mobile
      computing allows for a great deal of knowledge in a small package, creating a
      "walking library" with a mobile collection of data always accessible. There are
      many diverse types of PDAs, and this article discusses the history of PDAs,
      general purchasing issues, general PDA features, and the most significant
      differences between the Palm and the Windows CE operating systems.

PMID- 15255515
TI  - Review of technology: planning for the development of telesonography.
AB  - Teleradiology allows contemporaneous interpretation of imaging exams performed at
      some distance from the interpreting radiologist. The transmitted images are
      usually static. However, there is benefit to real-time review of full-motion
      ultrasound (US) exams as they are performed. Telesonography is transmission of
      full-motion sonographic data to a remote site. We hypothesize that US exams, read
      after having been compressed utilizing Motion Picture Experts Group version 4
      (MPEG-4) compression scheme, transmitted over the Internet as streaming
      multimedia, decompressed, and displayed, are equivalent in diagnostic accuracy to
      reading the examinations locally. MPEG-4 uses variable compression on each image
      frame to achieve a constant output bit rate. With less compression, the bit rate
      rises, and the only way the encoder can contain bit rate within the set bandwidth
      is by lowering frame rate or reducing image quality. We review the relevant
      technologies and industry standard components that will enable low-cost
      telesonography.

PMID- 15255516
TI  - Radiology: "killer app" for next generation networks?
AB  - The core principles of digital radiology were well developed by the end of the
      1980 s. During the following decade tremendous improvements in computer
      technology enabled realization of those principles at an affordable cost. In this
      decade work can focus on highly distributed radiology in the context of the
      integrated health care enterprise. Over the same period computer networking has
      evolved from a relatively obscure field used by a small number of researchers
      across low-speed serial links to a pervasive technology that affects nearly all
      facets of society. Development directions in network technology will ultimately
      provide end-to-end data paths with speeds that match or exceed the speeds of data
      paths within the local network and even within workstations. This article
      describes key developments in Next Generation Networks, potential obstacles, and
      scenarios in which digital radiology can become a "killer app" that helps to
      drive deployment of new network infrastructure.

PMID- 15255517
TI  - Integrating dictation with PACS to eliminate paper.
AB  - Five years ago our department migrated from a film-based imaging environment to a
      PACS-based environment. We discovered that our reliance on paper tracking forms
      for clinical history and dictation information was hindering our practice.
      Integrating dictation with PACS was one of three key components we needed to free
      ourselves from the tyranny of paper, the other two being an online worklist and
      an online patient history. We discuss our evolution to a (mostly) paperless
      reading room environment, our implementation, general performance, and future
      development plans, focusing on integrated dictation.

PMID- 15255518
TI  - Lung field segmenting in dual-energy subtraction chest X-ray images.
AB  - The purpose of this study was to develop and test a method to delineate lung
      field boundaries in dual-energy chest x-ray images. The segmenting method uses
      soft-tissue images and spatial frequency-dependent, background-subtracted images.
      Large-scale chest anatomy features are located and used to select the lung
      apices, the lateral lung boundaries, and the lung-mediastinum and lung-diaphragm
      boundaries. Extraneous parts of the contours are removed and they are joined to
      form complete lung boundaries. The reliability measure uses a statistical shape
      model to estimate the probability of occurrence of a contour. The method was
      experimentally tested with 30 human subject images. It has higher accuracy and
      specificity and a sensitivity parameter equal to the best previously reported
      method. The reliability measure is able to detect contours with unusual lung
      outlines or errors in the processing. The method exploits the characteristics of
      dual-energy subtraction images to improve lung field segmenting performance.

PMID- 15255519
TI  - Lossless compression of volumetric medical images with improved three-dimensional
      SPIHT algorithm.
AB  - This article presents a lossless compression of volumetric medical images with
      the improved three-dimensional (3-D) set partitioning in hierarchical tree
      (SPIHT) algorithm that searches on asymmetric trees. The tree structure links
      wavelet coefficients produced by 3-D reversible integer wavelet transforms.
      Experiments show that the lossless compression with the improved 3-D SPIHT gives
      improvement about 42% on average over two-dimensional techniques and is superior
      to those of prior results of 3-D techniques. In addition, we can easily apply
      different numbers of decomposition between the transaxial and axial dimensions,
      which is a desirable function when the coding unit of a group of slices is
      limited in size.

PMID- 15255521
TI  - Angiogenesis with biomaterial-based drug- and cell-delivery systems.
AB  - Angiogenesis, the formation of new blood vessels from existing ones, is an
      important event in several biological processes, including wound healing. It
      plays a key role in determining the final functionality and integration of any
      implanted medical device. In addition, angiogenesis is a required event for organ
      development and has been accepted as a rate-limiting step in engineering tissue
      replacements. Besides these regenerative processes, uncontrolled angiogenesis is
      also involved in a number of pathologies, including tumor growth and metastases.
      Like angiogenesis, biomaterials also play a role in wound healing after medical
      device implantation and in tissue engineering. Interactions between the device
      biomaterials and host tissue will factor into the final device integration.
      Additionally, tissue-engineering strategies utilize biomaterials to a great
      extent because the paradigm of tissue engineering involves the use of cells,
      growth factors and scaffolding matrices in order to regenerate or replace tissue.
      Since almost all tissues are three-dimensional, the biomaterial scaffold plays an
      integral role in the paradigm. This review will emphasize the influence of
      biomaterials on angiogenesis as it applies to medical device implantation, tissue
      engineering and therapies for pathological angiogenesis.

PMID- 15255520
TI  - A perceptual evaluation of JPEG 2000 image compression for digital mammography:
      contrast-detail characteristics.
AB  - In this investigation the effect of JPEG 2000 compression on the contrast-detail
      (CD) characteristics of digital mammography images was studied using an
      alternative forced choice (AFC) technique. Images of a contrast-detail phantom,
      acquired using a clinical full-field digital mammography system, were compressed
      using a commercially available software product (JPEG 2000). Data compression was
      achieved at ratios of 1:1, 10:1, 20:1, and 30:1 and the images were reviewed by
      seven observers on a high-resolution display. Psychophysical detection
      characteristics were first computed by fitting perception data using a maximum
      likelihood technique from which CD curves were derived at 50%, 62.5%, and 75%
      threshold levels. Statistical analysis indicated no significant difference in the
      perception of mean disk thickness up to 20:1 compression except for disk diameter
      of 1 mm. All other compression combinations exhibited significant degradation in
      CD characteristics.

PMID- 15255522
TI  - Silica-filled elastomer/methacrylate systems as soft liners.
AB  - Denture soft lining materials are compliant cushions used at the oral tissue
      denture interface. They are generally required to have sufficient compliance to
      redistribute mastication load, as well as an adequate modulus for long-term
      dimensional stability and control over the water uptake. This study investigated
      the effect of using silane treated fumed silica as a filler on the properties of
      experimental soft lining materials based on blends of isoprene-styrene (SIS)
      block co-polymer and mixtures of methyl methacrylate (MMA) and 1,6-hexandiol
      dimethacrylate (HDMA). The overall elastomer/monomer ratios were maintained,
      whereas the monomers ranged from 10 to 60% HDMA. The silica filler level was
      maintained at 10 wt% with respect to SIS. The properties investigated were the
      dynamic mechanical parameters of storage modulus (E') and tan delta as a function
      of temperature and the quasi-static mechanical parameters of ultimate tensile
      strength (UTS) and elongation to break (Eb) as well as absorption properties that
      were carried out in water and saline. In both unfilled and filled systems there
      was an increase in E' and a decrease in tan delta with an increase in HDMA.
      Silica addition tended to increase E' and substantially reduce tan delta in
      materials with less than 20% HDMA. UTS decreased with filler and HDMA content,
      however, Eb was greater for filled systems. Generally, in the long term, the
      water uptake decreased with increasing HDMA content and E'. The silanated silica
      further reduced the water uptake, indicating a cross-linking effect, thus
      increasing the restraining force on droplet growth. The uptake in saline was
      significantly reduced indicating an osmotically controlled uptake process.

PMID- 15255523
TI  - Characterization of a polyvinyl alcohol-hydrogel artificial articular cartilage
      prepared by injection molding.
AB  - We have developed a hip hemi-arthroplasty using polyvinyl alcohol-hydrogel (PVA
      H) as the treatment for hip joint disorders in which the lesion is limited to the
      joint surface. In previous studies, we characterized the biocompatibility and the
      mechanical properties of PVA-H as an arthroplasty material. To fix PVA-H firmly
      to the bone, we have devised an implant composed of PVA-H and porous titanium
      fiber mesh (TFM). However, because of poor infiltration of the PVA solution into
      the pores of the TFM when using the low temperature crystallization method, the
      strength of the PVA-H-TFM interface was insufficient. Consequently, the
      infiltration method was improved by adopting high-pressure injection molding.
      With this improved method, the bonding strength of the interface increased
      remarkably. However, as this injection molding requires high temperature, various
      mechanical properties of the PVA-H might change with this treatment in comparison
      with the previous method. The purpose of this study was to investigate the effect
      of high temperature treatment on the mechanical properties of PVA-H as artificial
      articular cartilage, the tensile test and friction test were performed about new
      PVA-H. The results showed no significant mechanical deterioration of the PVA-H.
      This certified that the injection-molding method did not induce the change of the
      mechanical properties of PVA-H and indicated the potential of hemi-arthroplasty
      using PVA-H by this method in the future.

PMID- 15255525
TI  - Preparation of cross-linked hyaluronic acid film using 2-chloro-1
      methylpyridinium iodide or water-soluble 1-ethyl-(3,3
      dimethylaminopropyl)carbodiimide.
AB  - In order to obtain much slower biodegradable films, which are often required for
      biomedical applications, we have developed a series of studies on heterogeneous
      cross-linking of hyaluronic acid (HA) films by using 2-chloro-1-methylpyridinium
      iodide (CMPI) or 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide (EDC) as cross
      linking reagents. From the in vitro degradation rate, we found that EDC cross
      linked HA films completely dissolved in PBS at 37 degrees C during the period of
      4-6 days. However, CMPI cross-linked HA films showed only a low percentage of
      weight loss over 30 days. This phenomenon could be explained from the mechanism
      of reaction between carboxyl group of HA and EDC. The latter reacted with
      carboxyl group to form an unstable intermediate O-acylurea, which showed a
      relatively low reactivity and quickly rearranged to form a stable N-acylurea.
      Thus, most of the EDC-activated carboxyl groups in HA were chemically transferred
      into N-acylurea or left as unreactive O-acylurea, and only a few of cross-linking
      bonds were formed between HA. On the other hand, the intermediate obtained from
      the reaction between carboxyl group and CMPI showed a relatively high reactivity
      and reacted with the hydroxyl group of the same and/or different molecules of HA
      to form an inter- and intramolecular esterification. Apparently, CMPI cross
      linked HA films have a much higher cross-linking density and constructed a more
      rigid three-dimensional network. Therefore, it produced HA films, which
      dramatically increased its enzymatic stability in aqueous solution of
      hyaluronidase. The obtained results from elemental analyses, FT-IR spectra and
      NMR spectra also indicate that acylurea groups were introduced into EDC-cross
      linked HA films.

PMID- 15255524
TI  - Effect of polyethylene glycol grafted onto islet capsules on prevention of
      splenocyte and cytokine attacks.
AB  - In the graft rejection of transplanted islets, the host's immune cells recognize
      the islets as antigens, which then stimulate the immune cells to begin the
      cytokine secretion and also the proliferation of immune cells. To prevent the
      recognition of islets by the immune cells, we grafted biocompatible polyethylene
      glycol (PEG) onto the collagen capsule of islets without incurring any changes in
      the morphology and function of islets. To evaluate the efficiency of PEG
      grafting, PEG-grafted islets were cultured with splenocytes consisting mainly of
      lymphocytes and macrophages. A splenocyte proliferation assessment using a BrdU
      incorporation assay showed that the PEG-grafted islets did not stimulate the
      splenocytes. In addition, the viability and microorganisms in islet cells of co
      cultured PEG-grafted islets were not altered. However, in the co-culture of free
      islets (control) splenocytes were stimulated; they mainly secreted TNF-alpha and
      strongly affected the viability and structure of free islets. Furthermore, when
      islets were treated with the rat recombinant TNF-alpha for 7 days, the
      viabilities of PEG-grafted and free islets were significantly damaged, although
      the viability of PEG-grafted islets was higher than that of free islets by nearly
      three times. These results demonstrate that PEG grafted on the surface of islets
      could prevent the recognition of islets by splenocytes, but could not completely
      protect islets from cytokines.

PMID- 15255526
TI  - Synthesis and characterization of novel polyurethane cationomers with dipeptide
      sequences and alkylammonium groups.
AB  - A synthetic approach to polyurethane cationomers containing S-pyroglutamyl-S
      glutamic acid dipeptide (S-PyGlu-S-Glu) and alkylammonium groups is presented.
      Two segmented polycations, based on polycaprolactone diol, isophorone
      diisocyanate and dipeptide together with N-methyldiethanolamine, subsequently
      quaternized with dodecylbromide, were synthesized and characterized by IR
      spectroscopy, GPC, DSC and reduced viscosity measurements. Such polycations
      exhibited excellent film forming properties and their soft elastomeric nature
      provides adequate physical properties. Optical rotation varying from +10
      (monomer) to -15 (polycation) could be associated with a configuration
      pertubation through the asymmetric carbon atoms of glutamic residues.
      Susceptibility of the cationic surface to heparinization and then to blood
      polymer interaction suggested an anticoagulant activity of the heparinized
      polymeric films.

PMID- 15255527
TI  - Electrospinning of chitosan solutions in acetic acid with poly(ethylene oxide).
AB  - Electrospinning of chitosan solutions with poly(ethylene oxide) (PEO) in an
      aqueous solution of 2 wt% acetic acid was studied. The properties of the
      chitosan/PEO solutions, including conductivity, surface tension and viscosity,
      were measured. Morphology of the electrospun chitosan/PEO was observed by using
      scanning electron micrographs. Results showed that the ultrafine fibers could be
      generated after addition of PEO in 2:1 or 1:1 mass ratios of chitosan to PEO from
      4-6 wt% chitosan/PEO solutions at 15 kV voltage, 20 cm capillary-collector
      distance and flow rate 0.1 ml/h. During electrospinning of the chitosan/PEO
      solutions, ultrafine fibers with diameters from 80 nm to 180 nm were obtained,
      while microfibers with visually thicker diameters could be formed as well.
      Results of X-ray photoelectron spectroscopy, Fourier transform infrared
      spectroscopy and differential scanning calorimeter exhibited the larger
      electrospun microfibers were almost entirely made from PEO, while the electrospun
      ultrafine fibers mainly contained chitosan.

PMID- 15255528
TI  - The troubles of zirconia.
AB  - A new ceramic material was introduced into clinical practice five years ago with
      the expectation that it would improve performance and give better fracture
      toughness and wear resistance. In reality, the reverse happened and far more
      failures have occurred. This article asks whether there are any lessons to be
      learnt.

PMID- 15255529
TI  - Patents and investors.
AB  - Patents can help attract funding as well as create additional revenue streams.

PMID- 15255530
TI  - Optimising medical elastomer performance.
AB  - The ability of DSC to detect and quantify the degree of cure is a major tool for
      optimising the property and processing of elastomer components. The rapid and
      information-rich OIT measurements can be applied in numerous ways to monitor and
      develop antioxidant packages. In addition, through some less applied tests,
      subtle differences between ionising radiation sources for sterilisation can be
      quantified and put to use in an advantageous way, for example, with reduction in
      surface tack and maintenance of mechanical strength in a surgical glove.

PMID- 15255531
TI  - Ethylene-oxide sterilisation aids speed to market.
AB  - Changes in the ethylene-oxide sterilisation process are providing manufacturers
      with greater speed to market. Developments that are reducing process times are
      reported here together with study findings for a number of product families.

PMID- 15255532
TI  - ISO 11137, requirements for radiation sterilisation: current revisions.
AB  - The major changes that are expected in a revised standard on radiation
      sterilisation are discussed. Manufacturers should anticipate some challenges in
      meeting the proposed requirements.

PMID- 15255533
TI  - Choosing a silicone adhesive and treatment system.
AB  - As devices become smaller and bonds more critical, choosing the right adhesive
      system may be essential to the success of the device. This article investigates
      some adhesives and primers used to adhere difficult substrates.

PMID- 15255534
TI  - A three-axis accelerometer.
AB  - The development of a three-axis accelerometer that can simultaneously measure
      acceleration in all three directions is to be utilised in a range of emerging
      applications.

PMID- 15255535
TI  - A novel system for monitoring organs for transplant.
AB  - It has been established in animal tests that this monitoring can be used as a
      reliable indicator of organ viability prior to implantation. The complete system
      has an easy-to-use interface, integrates seamlessly in a transport cool-box and
      conducts continuous, minimally invasive monitoring of the organ, making it a
      suitable tool for its intended clinical application. The system constitutes the
      starting point of a new line of equipment that, using custom multiprobe
      microsensors as core elements, will prompt the path towards new biomedical
      application niches in the field of microsystems.

PMID- 15255536
TI  - Beyond the US submisson process.
AB  - After expending considerable effort to comply with United States (US) marketing
      authorisation regulations, a company launched its first product on the US market.
      Unfortunately, the company failed to comply with other applicable US regulations,
      which led to a delay in the US product introduction and FDA postmarketing
      enforcement actions against the product. This article discusses ways that
      companies can prevent this from happening.

PMID- 15255537
TI  - Informatics and standardisation.

PMID- 15255538
TI  - Industry economics in the United States.
AB  - Demand for medical equipment in the United States (US) is projected to grow by 8%
      between 2001 and 2006, to reach 105 billion dollars. In 2001,the market was
      valued at 71.4 billion dollars, based on an annual growth of 7.5% between 1996
      and 2001, according to The Freedonia Group. Product innovation and the growing
      ageing population is driving the industry, despite health-care cost containment
      measures. Medical and surgical instruments continue to be the largest sector,
      which is expected to grow to 30.5 billion dollars in 2006. However,
      electromedical/electrotherapeutic apparatus will remain the fastest growing
      sector, with annual gains of 10.8% predicted for this period.

PMID- 15255539
TI  - Predictors of random sextant biopsy outcome in screened men with PSA > 4 ng/mL
      and a negative sextant biopsy at previous screening. Experience in a population
      based screening program in Florence.
AB  - The aim of this study was to evaluate possible pedictors of the outcome of repeat
      random sextant biopsy of the prostate prompted by a rise in prostate-specific
      antigen (PSA). Random biopsies performed for PSA elevation (>4 ng/mL) in the
      course of a randomized study of screening efficacy were reviewed, and 87
      consecutive biopsies (carcinoma = 13, high-grade prostatic intraepithelial
      neoplasia = 6, negative = 68) performed in subjects with a negative random biopsy
      at the previous screening round were considered. Findings at digital rectal
      examination or transrectal ultrasonography and total PSA value were not useful
      predictors of repeat biopsy outcome, whereas PSA velocity was significantly
      associated with biopsy outcome. The positive predictive value for a cancer biopsy
      was 2.7% (1/36), 28.5% (2/7), and 22.7% (10/44) for PSA velocity values of <0.1,
      0.1-0.19, and >0.19 ng/mL/yr, respectively. A cutoff of 0.1 ng/mL/yr for PSA
      velocity would have allowed to avoid approximately half (35/74 = 47.2%) of the
      benign biopsies while decreasing the sensitivity by 7.6% (1/13), and is thus
      suggested as a possible criterion for the indication of repeat random biopsy for
      persistent PSA elevation.

PMID- 15255540
TI  - Frequent detection and immunophenotyping of prostate-derived cell clusters in the
      peripheral blood of prostate cancer patients.
AB  - BACKGROUND: Recent scientific studies have failed to determine parameters for the
      assessment of prostate cancer aggressiveness. The present study deals with the
      detection of blood-borne cancer cells based on polymerase chain reaction (PCR)
      and cell enrichment methods. The contradictory results reported in the literature
      have called into question the clinical usefulness of this diagnostic method in
      the preoperative staging of clinically localized prostate cancer. METHODS: We
      established a combined method of density gradient centrifugation and
      immunomagnetic separation using epithelium-specific antibodies, i.e.
      cytokeratins, to isolate prostate-derived circulating cells from the peripheral
      blood of patients with prostate cancer. Isolated cells were characterized by DNA
      staining and immunocytochemistry using antibodies for the detection of prostate
      specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and
      apoptosis-associated proteins (M30, c-FasR). RESULTS: We applied these methods to
      68 prostate cancer patients and were able to isolate cell clusters in 98%.
      Immunophenotypic and morphological characterization of PSA-positive prostate
      derived cell clusters found in the peripheral blood of prostate cancer patients
      showed two main populations: 1) in 35% of the investigated prostate cancer
      patients we detected rounded cell aggregates of probable cancer cells expressing
      proliferation-associated proteins and lacking apoptosis-associated protein
      expression; 2) in all cases there was a high frequency of circulating dysmorphic
      cell clusters positive for apoptosis-associated protein expression. CONCLUSION:
      Our results demonstrate the existence of at least two different types of blood
      borne prostate-derived circulating cell clusters. Of these, only the less
      frequent, round, small cell clusters harbor features that are probably necessary
      for the cells to survive for metastatic spread.

PMID- 15255541
TI  - Gene transcript assay by real-time RT-PCR in epithelial breast cancer cells
      selected by laser microdissection.
AB  - The cell type heterogeneity within clinical cancer tissue samples may affect the
      accuracy of gene expression analysis. In order to validate our laser
      microdissection (LMD) method using the Leica AS LMD system (LEICA Microsystems),
      we compared the mRNA levels of three major genes involved in breast cancer
      (ERalpha, PR, HER2), measured by means of real-time quantitative RT-PCR, in 5000
      microdissected malignant epithelial cells and in corresponding bulk tumor
      homogenates from 14 patients. We also compared the mRNA level results to protein
      expression measured by immunohistochemistry (IHC) on the same tumors. For the
      three genes, significant correlations were found between mRNA results obtained on
      microdissected cells and IHC. Comparison between IHC and mRNA results obtained on
      microdissected cells and bulk tumors showed that in all cases microdissection
      enhanced the sensitivity of assessing target gene transcript levels and was
      essential for their accurate evaluation in heterogeneous tumors.

PMID- 15255542
TI  - MUC3 and MCA serum levels and steroid receptor content in breast cancer.
AB  - Mucins are an important class of complex glycoproteins expressed by many
      epithelial cells and their malignant counterparts. The aim of this study was to
      determine the serum levels of MUC3 and mucin-like carcinoma-associated antigen
      (MCA) in patients with primary breast cancer and to analyze the possible
      relationships between these two mucins and the steroid receptor status. The
      preoperative basal serum levels of MUC3 (ELISA assay with monoclonal antibody
      1143/B7) and MCA (EIA assay with anti-MCA mouse monoclonal antibody b-12) were
      determined in 44 patients with breast cancer while estrogen receptor (ER) and
      progesterone receptor (PgR) levels were measured by the dextran-coated charcoal
      method in the cytosol of neoplastic tissue. MUC3 was expressed in 43/44 serum
      samples while high MCA serum levels were found in 16/44 only; the mean values of
      both markers did not correlate with menopausal status, tumor size, nodal
      involvement or ER. The only significant difference observed was a lower median
      value of MCA in patients with small tumors (T1-T2). No statistically significant
      correlation between MUC3 and MCA, MUC3 and ER or MCA and ER was observed; a
      statistically significant direct correlation between MUC3 and PgR+ status and a
      statistically significant inverse correlation between MCA and PgR+ were observed.
      Our results suggest that further investigations are necessary to establish
      whether progesterone can modulate MUC3 and MCA expression in breast cancer.

PMID- 15255543
TI  - TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer
      and chronic pancreatitis.
AB  - The aim of this study was to assess the value of TPS and CA 19-9 in a long-term
      follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients
      with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis
      the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of
      them. In one patient a dramatic increase in the TPS concentration (820 U/L) was
      measured at the last follow-up visit (after 8.6 months), which led to the
      detection of PC. In all patients with PC the preoperative TPS level exceeded 200
      U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple
      operation 11 patients showed no evidence of disease and in eight of these
      patients both TPS and CA 19-9 were within the reference range; however, in three
      patients liver metastases were detected after 8-24 months from the last tumor
      marker measurement. In four of the 15 patients both markers were elevated at the
      end of the follow-up period and distant metastases were clinically confirmed. Our
      results indicate that in patients with CP and PC undergoing long-term follow-up,
      TPS reflects the clinical status of patients more accurately than CA 19-9.

PMID- 15255544
TI  - Comparison of expression of cathepsins B and L and MMP2 in endothelial cells and
      in capillary sprouting in collagen gel.
AB  - The lysosomal cysteine proteinases cathepsins B and L are known to play an
      important role in the invasive growth of tumor cells, but their association with
      angiogenesis has been less well studied. The aim of this study was to determine
      the possible role of endothelial cell-associated cathepsins B and L in induced
      capillary growth in the aorta ring model of angiogenesis. Specific inhibitors of
      cysteine proteinases did not inhibit capillary growth in aorta ring culture and
      only slightly inhibited the degradation of surrounding collagen. In contrast,
      strong inhibition of both processes by the matrix metalloproteinase inhibitor BB
      94 was observed, indicating the importance of endogenous MMP production in
      angiogenesis. In support of this finding, we demonstrated a significant increase
      in endogenous endothelial mRNA of MMP2, but not of cathepsins B and L, in
      proliferating primary human dermal microvascular endothelial cells (HMVEC-d) in
      culture. However, MMP2 mRNA expression was increased only when the cells were
      embedded in collagen but not when they were grown on plastic, regardless of the
      addition of the growth factors VEGF or bFGF. Moreover, on plastic the impairment
      of MMP2 induction by growth factors was observed. The differential effect of
      growth factors implies the crosstalk with integrin signaling as a consequence of
      binding to the different matrix. This study suggests that endothelial cell
      associated cathepsins B and L are not involved in the invasive growth of
      capillaries from existing blood vessels and that the presence of collagen is
      necessary for MMP2 expression in endothelial cells.

PMID- 15255545
TI  - Serum levels of tumor necrosis factor alpha correlate with response to
      neoadjuvant chemotherapy in locally advanced breast cancer.
AB  - It has been shown that serum levels of tumor necrosis factor alpha (TNF-alpha)
      are increased in breast cancer patients. There are few data available on the
      reduction of serum levels of this cytokine following chemotherapy. The aim of
      this study was to determine the effect of neoadjuvant chemotherapy on serum
      concentrations of TNF-alpha and the relation to response rates in locally
      advanced breast cancer. Twenty consecutive patients with non-inflammatory stage
      III-B breast cancer achieving a partial or complete clinical response to three
      courses of neoadjuvant chemotherapy followed by modified radical mastectomy were
      prospectively included in the study and evaluated. Sera were collected before the
      start and after the termination of chemotherapy. Serum concentrations of TNF
      alpha were measured by an ELISA method. The pathological response rates were also
      evaluated and recorded. The control group consisted of 12 healthy age-matched
      women. The mean pre-treatment TNF-alpha value of breast cancer patients was 15.9
      +/- 0.9 pg/mL while it was 5.8 +/- 1.7 pg/mL in the control group; the difference
      was statistically significant (p < 0.0001). The serum levels of TNF-alpha were
      markedly decreased in patients with partial and complete responses compared to
      pre-treatment values (p < 0.0001). There was also a difference in TNF-alpha
      levels in patients with partial vs complete responses (p < 0.0001). The relative
      change between pre- and post-treatment values correlated significantly with the
      type of response (p = 0.004). These results suggest that the serum concentration
      of TNF-alpha can be an indicator of response and could be used in clinical
      decision-making for patients with locally advanced breast cancer.

PMID- 15255546
TI  - Efficacy of cancer chemotherapy in relation to the pretreatment number of
      lymphocytes in patients with metastatic solid tumors.
AB  - The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis
      in terms of survival in advanced cancer patients. This finding is not surprising
      because of the fundamental role of lymphocytes in mediating tumor cell
      destruction. Despite the importance of lymphocytes in the pathogenesis of cancer,
      there are only few data about the profile and the function of lymphocytes during
      the various antitumor therapies, and in particular the relation between
      lymphocyte pretreatment number and response to chemotherapy remains to be
      established. The present study was performed to evaluate whether the evidence of
      lymphocytopenia before the onset of treatment may influence the efficacy of
      chemotherapy in metastatic cancer patients affected by the most frequent tumor
      types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63;
      breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The
      chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and
      folates in untreated colorectal cancer, weekly irinotecan in pretreated
      colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung
      cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast
      cancer patients who had been previously treated with anthracyclines. Lymphocyte
      count was considered to be abnormally low for values below 1500/mm3.
      Lymphocytopenia was found in 79/183 (43%) patients, without any significant
      differences in relation to tumor histology. A complete response (CR) was achieved
      in 6/104 patients with a normal lymphocyte count and in none of the 79
      lymphocytopenic patients. A partial response (PR) was obtained in 39 patients
      with a normal lymphocyte count and in only eight patients with a low lymphocyte
      count prior to therapy. Therefore, irrespective of the type of chemotherapy, the
      objective tumor response rate (CR + PR) in lymphocytopenic patients was
      significantly lower than in patients with normal pretreatment lymphocyte counts
      (8/79 vs 45/104; p < 0.001). This study shows that the evidence of
      lymphocytopenia prior to chemotherapy is associated with a lower efficacy of
      treatment in terms of objective tumor regression rates in patients with
      metastatic solid tumors, and suggests that the action of chemotherapy may depend
      at least in part on an interaction with the antitumor immunity. Pretreatment
      lymphocyte count may represent a new, simple biological marker to be taken into
      consideration by oncologists in the chemotherapeutic treatment of metastatic
      cancer.

PMID- 15255547
TI  - Statistical diagnostics emerging from external quality control of real-time PCR.
AB  - Besides the application of conventional qualitative PCR as a valuable tool to
      enrich or identify specific sequences of nucleic acids, a new revolutionary
      technique for quantitative PCR determination has been introduced recently. It is
      based on real-time detection of PCR products revealed as a homogeneous
      accumulating signal generated by specific dyes. However, as far as we know, the
      influence of the variability of this technique on the reliability of the
      quantitative assay has not been thoroughly investigated. A national program of
      external quality assurance (EQA) for real-time PCR determination involving 42
      Italian laboratories has been developed to assess the analytical performance of
      real-time PCR procedures. Participants were asked to perform a conventional
      experiment based on the use of an external reference curve (standard curve) for
      real-time detection of three cDNA samples with different concentrations of a
      specific target. In this paper the main analytical features of the standard curve
      have been investigated in an attempt to produce statistical diagnostics emerging
      from external quality control. Specific control charts were drawn to help
      biochemists take technical decisions aimed at improving the performance of their
      laboratories. Overall, our results indicated a subset of seven laboratories whose
      performance appeared to be markedly outside the limits for at least one of the
      standard curve features investigated. Our findings suggest the usefulness of the
      approach presented here for monitoring the heterogeneity of results produced by
      different laboratories and for selecting those laboratories that need technical
      advice on their performance.

PMID- 15255548
TI  - Interobserver reproducibility of immunohistochemical HER-2/neu evaluation in
      human breast cancer: the real-world experience.
AB  - In spite of the large number of studies on technical problems affecting the
      interlaboratory reproducibility of IHC HER-2/neu determination, only little is
      known about factors limiting the intra- and interobserver reproducibility in the
      actual practice of HER-2/neu expression analysis. The aim of the present INQAT
      study was to evaluate the intra- and inter-observer reproducibility of IHC HER-2
      analysis among pathologists routinely working in Italian laboratories. Twenty
      immunostained slides were distributed to 12 pathologists who had to report, for
      each slide, the semiquantitative analysis of the percentage of immunopositive
      cells and the qualitative evaluation of the intensity of membrane staining. The
      intra- and interobserver reproducibility as well as the reproducibility between
      each laboratory and the reference values were quantified adopting an approach
      based on computation of the weighted kappa statistic (Kw). Additionally, in order
      to evaluate the contribution of each category to the overall agreement, the kappa
      category-specific statistics (Kcs) were estimated for both classification
      criteria by jointly considering all the participating laboratories. The
      intraobserver analyses showed a satisfactory level of reproducibility for both
      the percentage of positive cells (median Kw, 0.94; range: 0.80-0.96) and membrane
      staining (median Kw, 0.86; range: 0.78-0.96). Similarly, a fairly good level of
      reproducibility for the percentage of cells (median Kw, 0.89; range, 0.73-0.96)
      and the intensity of membrane staining (median Kw, 0.84; range, 0.72-0.92) were
      observed from comparisons with reference values. When all possible pairwise
      comparisons were performed, a satisfactory level of interobserver reproducibility
      was found for most laboratories. Kw values varied between 0.51 and 0.98 (median
      Kw, 0.80) and between 0.61 and 0.94 (median Kw, 0.81) for semiquantitative and
      qualitative measurements, respectively. Analysis of the contribution of the
      extreme categories to the overall agreement showed a substantial or almost
      perfect agreement for both classification criteria. Conversely, the contribution
      of intermediate categories appeared to be scarce or slight for the percentage of
      immunostained cells and slight or fair for the intensity of membrane staining. We
      conclude that, overall, the interobserver reproducibility in IHC analysis of HER
      2/neu expression is satisfactory, although classification of the intermediate
      categories is problematic, both with regard to the percentage of immunostained
      cells and the intensity of membrane staining.

PMID- 15255550
TI  - Lack of association of CYP1 B1*3 polymorphism and ovarian cancer in a Caucasian
      population.
AB  - CYP1B1 is the enzyme with the highest efficiency of conversion of estradiol to 4
      hydroxyestradiol in humans. This metabolite has a well-known carcinogenic effect
      interacting with genomic DNA and has been hypothesized to be partly responsible
      for the role played by estrogens in ovarian cancer development. A polymorphism
      has been described for this enzyme causing a Leu to Val substitution in position
      432 (CYP1B1*3). The Val432 allele has a higher efficiency of conversion of
      estradiol to 4-hydroxyestradiol and has been reported to increase the risk of
      ovarian cancer. A previous study reported a higher, significant prevalence of
      CYP1B1*3 polymorphism in ovarian cancer patients of mixed ethnicity. The aim of
      this study was to investigate the role of CYP1B1*3 polymorphism as a risk factor
      for ovarian cancer in a Caucasian population. The polymorphism frequency was
      determined in 223 cases of ovarian cancer and compared with that of 280 healthy
      female blood donors. Genetic analysis was performed on genomic DNA from PBMC and
      RFLP methods were used for mutation detection. No significant difference between
      cases and controls was found. These results do not support a favoring role of
      CYP1B1*3 in ovarian cancer development in our population.

PMID- 15255549
TI  - Improvement of liver cancer detection with simultaneous assessment of circulating
      levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes.
AB  - We assessed the presence of alpha-fetoprotein (AFP) complexed with IgM (AFP-IgM
      IC) in serum of patients affected by hepatocellular carcinoma (HCC), cirrhosis
      and chronic hepatitis as well as in healthy subjects by means of a dedicated
      ELISA assay. The amount of AFP-IgM IC was expressed in arbitrary units (AU) on a
      reference standard curve. Free AFP (FAFP) levels were determined in parallel in
      each sample by means of an automated immunoassay system. The mean serum
      concentration of AFP-IgM IC was significantly higher in HCC patients (mean +/-
      SD: 1378.3 +/- 2935.7 AU/mL) than in cirrhotic patients (129.8 +/- 261.4 AU/mL)
      and in patients with chronic hepatitis (80.9 +/- 168.9 AU/mL) (p < 0.01). HCC
      patients had FAFP values above the 20 ng/mL cutoff in 44% of cases (22/50) and
      AFP-IgM IC values above the 120 AU/mL cutoff in 60% of cases (30/50). The
      occurrence of the free and IgM-complexed form of circulating AFP did not overlap,
      and 82% of patients (41/50) were positive for at least one marker. The results
      indicate that AFP-IgM IC is a complementary serological marker to FAFP and that
      the combination of these biomarkers may be useful in the diagnosis of liver
      cancer.

PMID- 15255551
TI  - Are plasma insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP
      3) useful markers of prostate cancer?
AB  - Increased concentrations of insulin-like growth factor I (IGF-I) and decreased
      insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been
      proposed as markers of prostate cancer (CaP). The evidence for this, however, is
      contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen
      (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy
      controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3
      ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/-
      36.1 ng/mL; n=46), but the differences between the three groups were not
      statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP
      (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p =
      0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL;
      n=59), but the difference between the two groups of patients was not significant
      (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were
      significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001).
      Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0
      ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were
      76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA
      for CaP detection.

PMID- 15255552
TI  - The correlation between fetal hemoglobin and outcome in non-Hodgkin's lymphoma.

PMID- 15255553
TI  - Blood level of phosphoglycerate kinase does not correlate with presence or extent
      of tumor.

PMID- 15255554
TI  - Levofloxacin, a broad spectrum anti-infective: from Streptococcus pneumoniae to
      Pseudomonas aeruginosa.

PMID- 15255555
TI  - Levofloxacin PK/PD: from sequential therapy model to high dosage for critical
      patients.

PMID- 15255556
TI  - Role of levofloxacin in the treatment of lower respiratory tract infections
      (LRTIs).

PMID- 15255557
TI  - Clinical experience with levofloxacin in the treatment of pneumonia in ICU
      patients.

PMID- 15255558
TI  - Levofloxacin in the treatment of urinary tract infections and prostatitis.

PMID- 15255559
TI  - Levofloxacin: a suitable option for the infectious disease consultant.

PMID- 15255560
TI  - Electromagnetic fields and health effects--epidemiologic studies of cancer,
      diseases of the central nervous system and arrhythmia-related heart disease.
AB  - This epidemiologic investigation comprised separate studies of the risk of
      cancer, cause-specific mortality rates, risks for neurodegenerative diseases, and
      the risk of arrhythmia-related heart disease among employees exposed to extremely
      low-frequency (50-Hz) electromagnetic fields (EMF) in the Danish utility
      industry. All the employees in this industry were followed-up in several
      registers. The risk of disease was analyzed in relation to occupational exposure
      to EMF, latency, and duration of employment. A specific job-exposure matrix was
      developed and validated by comparison with direct measurements of EMF during a
      workday. Linkage with the Danish Cancer Register did not identify increased risks
      for the cancers suggested a priori to be associated with exposure to EMF,
      including leukemia, brain tumors, and breast cancer. Significantly increased
      risks for lung cancer and mesothelioma were identified for workers highly exposed
      to asbestos. Linkage with the National Mortality Register revealed a
      significantly increased overall mortality rate from amyotrophic lateral sclerosis
      (ALS), with an increasing trend with duration of employment and EMF exposure. In
      addition, a significantly increased mortality rate from electric accidents was
      observed. It was hypothesized that the observation of increased mortality from
      ALS was associated with exposure to EMF or electric shocks. No increased
      mortality rate from cardiovascular or cerebrovascular disease was observed.
      Linkage with the National Hospital Register also revealed an increased risk of
      ALS and, thereby confirmed the finding of an increased mortality rate for this
      disease in the previous study. Linkage of the cohort with the Multiple Sclerosis
      Register revealed an increased risk of multiple sclerosis, which was not,
      however, significant. Linkage with the Pacemaker Register showed no increased
      risk of severe arrhythmia-related heart disease. The second part of the study
      included the establishment of a large, nationwide cohort of mobile phone
      subscribers comprising some 420 000 persons. No increased risk was observed for
      the cancers considered a priori to be possibly associated with the radiofrequency
      fields emitted by mobile phones, which were brain tumors, including acoustic
      neuroma, salivary gland tumors, and leukemia. The data were analyzed by duration
      of phone use, latency, system used (NMT, GSM or both) and age at first
      subscription. A study of the incidence of ocular malignant melanoma in comparison
      with the annual increase among the mobile phone subscribers showed a highly
      stable incidence rate for this rare cancer in Denmark over close to 50 years of
      registration. On the basis of these studies and the scientific literature, it is
      concluded that occupational exposure to 50-Hz EMF is not associated with an
      increased risk of cancer, but that these fields, electric shocks, or some other
      unknown factor related to alternating current electricity may be associated with
      the risk of ALS. There is no clear evidence that 50-Hz EMF is associated with
      other neurodegenerative or cardiovascular diseases. At present, there is little,
      if any, evidence that the use of mobile phones is associated with cancer in
      adults, including brain tumors, acoustic neuroma, cancer of the salivary glands,
      leukemia, or malignant melanoma of the eye.

PMID- 15255562
TI  - Intern year - what to expect.

PMID- 15255561
TI  - 2000 steps towards obesity control.

PMID- 15255563
TI  - The diagnosis and management of common inherited bleeding disorders.
AB  - Inherited bleeding disorders can be associated with significant morbidity and
      mortality. Bleeding episodes can be safely and effectively managed in the
      majority of patients provided the coagulation defect is identified and corrected
      with the appropriate replacement therapy. It is imperative that these patients
      are treated in centres that can provide full coagulation support, and a
      comprehensive care plan is formulated for each individual.

PMID- 15255564
TI  - Childhood immunisation in Ireland: where to now?

PMID- 15255565
TI  - Management of parapharyngeal space tumors.
AB  - In this study, we aimed to investigate the influence of the surgical approaches
      for the parapharyngeal space tumors. Eighteen patients with parapharyngeal space
      tumors diagnosed and treated at our clinic between 1992 and 2001 were included in
      this study. Surgical techniques used included transcervical, transparotid,
      transcervical-transmandibular, and infratemporal-A approaches depending on tumor
      size, location, vascularity, and malignant potential. Postoperative radiation
      therapy was applied in all malignant tumor. Postoperative morbidity,
      complications, and recurrence were evaluated. We found that 55.6 % of the PPS
      tumor were of salivary gland origin, 27.8 % were neurogenic, and 16.6% were
      miscellaneous. Of the four surgical techniques, transcervical approach were used
      most commonly. Postoperative morbidities were at acceptable levels. Our surgical
      survival rates were 100% for benign and 40% for malignant PPS tumors after a mean
      follow-up of 54 months.

PMID- 15255566
TI  - Consumer satisfaction with child health clinics.
AB  - Consumer satisfaction surveys are used to assist in monitoring the quality of
      health care service delivery. In order to capture the views of those attending
      child health clinics in the community setting, a cohort of attendees to child
      health clinics in a health board region was sent a pre-piloted questionnaire
      enquiring about the clinic type attended, appointment details, facilities and
      environment of the health centre attended and experiences of communication and
      information at the clinic. Of 3,424 parents/guardians contacted, 2,402 (70.1%)
      replied. Two thousand (83.3%) had an appointment, with 61.1% attending first
      appointment within 3 months of referral. Median time spent in the centre was 25.0
      minutes (ranging from 5 to 150 minutes). Respondents were satisfied with
      structural facilities with the exception of baby-changing facilities. Respondents
      agreed that their child's condition (92.1 %) and treatment options (88.7%) were
      fully explained, with adequate time for discussion (87.8%). Only 44% (n=736)
      reported receiving written takeaway information regarding their child's
      condition. Respondents agreed their child was put at ease by staff (85.7%), and
      the visit was worthwhile (93.9%). This study has identified key areas where
      administration and health care professionals can improve the quality of what is
      already perceived to be a good service.

PMID- 15255567
TI  - Management of sudden sensorineural hearing loss - a national survey.
AB  - The management of Sudden Sensorineural Hearing loss is a controversial issue and
      there is no universally agreed protocol in its management The aim of this study
      was to ascertain the referral trends, treatment strategies, and outcome of
      treatment adopted by the Consultant Otorhinolarygologists in this country. A
      postal questionnaire was sent to all 32 Consultants in the Republic of Ireland,
      which achieved 21(65.62%) responses. Patients were referred to 13(61.9%)
      respondents within two weeks of the onset of symptoms and 3(14.28%) Consultants
      were referred patients within twenty four hours of the onset of symptoms. All
      specialists routinely performed full blood count and erythrocyte sedimentation
      rate, 15(71.42%) routinely assess fasting blood sugar and 5(23.80%) investigate
      fasting lipids and perform a syphilis screen. MR imaging to outrule vestibular
      schwanoma is performed by 11(52.38%) respondents. When treated within two weeks
      of the symptoms 6(28.57%) of the respondents were optimistic about recovery of
      hearing upon treatment whereas 2(9.52%) considered recovery of useful hearing
      less likely if treated more than two weeks after onset The triple therapy with
      oral vasodilators, oral steroids, and Carbogen inhalation was favoured by
      9(42.85%). Oral steroid was the sole therapeutic modality by 4(19.04%). The
      opinion of Consultants was that the referral trend from the primary care
      physician is appropriate and 20(95.23%). Consultants considered an optimistic
      outcome if treated within two weeks. The investigations and management protocol
      for sudden sensorineural hearing loss is not uniform which is consistent with the
      treatment strategies world wide.

PMID- 15255568
TI  - Choriocarcinoma-presenting as a primary lesion of the cervix.
AB  - A 25 year old nulliparous Russian lady presented to the hospital complaining of
      abdominal pain and mild vaginal bleeding. In 1999 she was diagnosed with a molar
      gestation and required a dilatation and curettage. On this occasion, Beta human
      Chorionic Gonadotrophin (BhCG) levels were elevated and a trans-vaginal
      ultrasound scan suggested the presence of a left-sided pelvic mass.
      Investigations confirmed the presence of a choriocarcinoma of the cervix.
      Complete assessment by a multidisciplinary team was performed and chemotherapy
      (methotrexate) was commenced. This case of a twenty-five year old nulliparous
      woman highlights the importance of appropriate follow-up in cases of irregular
      genital tract bleeding with a past history of trophoblastic disease.

PMID- 15255569
TI  - The career plans of Irish interns: results of a national survey.
AB  - In anticipation of major changes in medical manpower in Ireland, we surveyed all
      interns about their career plans. Three hundred (65% of those surveyed)
      responded. There were clear gender differences in career plans and overall, only
      15% planned a career in general practice. There was a negative perception about
      the quality of postgraduate training in Ireland and 93% planned to go overseas
      for training. These findings need to influence the debate on medical manpower and
      postgraduate training.

PMID- 15255570
TI  - Sagittal sinus thrombosis in a migraineur: differential diagnosis of headaches.

PMID- 15255571
TI  - Oral diamonds: a new potential airway foreign body.

PMID- 15255572
TI  - European Working Time Directive - IMO advice to consultants.

PMID- 15255573
TI  - Freedom of movement in an enlarged union.

PMID- 15255574
TI  - Attention deficit hyperactivity disorder and cardiovascular functioning.

PMID- 15255575
TI  - Intravenous fluid therapy.

PMID- 15255576
TI  - Testing madness.

PMID- 15255577
TI  - Leading to lead.

PMID- 15255579
TI  - Magnetic soot.

PMID- 15255578
TI  - Mickey has two moms.

PMID- 15255580
TI  - Baby talk beginnings.

PMID- 15255581
TI  - Growing pains.

PMID- 15255583
TI  - Undercutting fairness.

PMID- 15255582
TI  - Bugging for guidance.

PMID- 15255584
TI  - Overcoming self.

PMID- 15255585
TI  - If it's broke, fix it.

PMID- 15255587
TI  - Doom and gloom by 2100.

PMID- 15255586
TI  - God's number is up.

PMID- 15255588
TI  - The extraordinary deaths of ordinary stars.

PMID- 15255589
TI  - Gene doping.

PMID- 15255590
TI  - Magnetic field nanosensors.

PMID- 15255591
TI  - When methane made climate.

PMID- 15255593
TI  - The shapes of space.

PMID- 15255594
TI  - The mystery of the Voynich manuscript.

PMID- 15255592
TI  - Detecting mad cow disease.

PMID- 15255595
TI  - Big air.

PMID- 15255596
TI  - Stars atop a silent volcano.

PMID- 15255597
TI  - Why do people snore?

PMID- 15255598
TI  - What kind of patterns does the Search for Extraterrestrial Intelligence (SETI)
      look for?

PMID- 15255599
TI  - Role of vessel factor in oxygen uptake study (an addendum).

PMID- 15255600
TI  - Post-irradiation free radical generation: evidence from the conversion of
      xanthine dehydrogenase into xanthine oxidase.
AB  - The xanthine oxidoreductase (XOR) system which consists of xanthine dehydrogenase
      (XDH) and xathine oxidase (XO), is one of the major sources of free radicals in
      biological systems. The XOR system is pre-dominantly present as XDH in normal
      tissues and converts into the free radical generating XO-form in the damaged
      tissue. Therefore, the XO-form of the XOR system is expected to be mainly found
      in radiolytically damaged tissues. In such an event, XO may catalyze the
      generation of free radicals and potentiate radiation effects in the post
      irradiation period. Recent findings on the effect of ionizing radiation on the
      XOR system in the liver of mice, peroxidative damage and lactate dehydrogenase
      support this possibility. From these results it has been hypothesized that free
      radical generating systems could be activated in the radiolytically damaged cell
      and in turn contribute to the cause and complications of late effects and their
      persistence in post-irradiation period. This aspect may have great significance
      in the understanding of radiation-induced damages. It may also have serious
      implication in various fields like radiation therapy, health physics,
      carcinogenesis, space travelling radiation exposures and post nuclear accident
      care. Further, it is suggested that efforts need to be made to search more
      system(s) which could be activated particularly at lower doses of radiation to
      generate free radicals in the post-exposure period.

PMID- 15255601
TI  - Virus induced chromosomal abnormalities in Chinese hamster lung cell line and
      human peripheral blood leukocyte culture.
AB  - Chinese hamster lung (CHL) cells were susceptible to Herpes Simplex type-1 and
      Chandipura viruses; which induced chromosomal abnormalities in these cells.
      Chromosomal changes induced in these cells were specific. The cells were
      refractory to measles virus and chromosomal abnormalities were not detected after
      inoculation of the virus. On the other hand human peripheral blood (HPB)
      leukocytes were susceptible to all the 3 viruses studied and exhibited
      chromosomal abnormalities upon infection. The aberrations induced in HPBL
      cultures were random. The results suggest that a virus could induce chromosomal
      changes only in susceptible cells. This is the first report of comparative in
      vitro study on chromosomes.

PMID- 15255602
TI  - Effect of dietary zinc deficiency on metallothionein concentration of epididymal
      luminal fluids of weanling Wistar albino rats.
AB  - Metallothionein (NIT) and zinc concentrations have been estimated in luminal
      fluids of caput/corpus and cauda epididymis and serum of zinc deficient (ZD),
      pairfed (PF) and control--ad libitum fed (ZC) groups of Wistar rats. MT decreased
      significantly in luminal fluids of caput corpus and cauda epididymis and serum of
      zinc deficient rats as compared to their respective controls. However, the
      decrease was non-significant in luminal fluids of corpus epididymis and serum of
      4-weeks zinc deficient animals as compared to their control. Zinc levels also
      declined significantly in luminal fluids of epididymis and serum of zinc
      deficient rats as compared to their respective pairfed and control groups. Thus
      zinc deficiency state reduces zinc and MT concentrations in luminal fluid of
      epididymis and serum.

PMID- 15255603
TI  - Generation and characterization of monoclonal antibodies to protective antigen of
      Bacillus anthracis.
AB  - Monoclonal antibodies (MoAbs) were generated following immunization of BALB/c
      mice with protective antigen (PA) of B. anthracis. Five clones reactive to this
      protein were stabilized and preserved. These MoAbs could detect nanogram levels
      of PA when tested in ELISA. In Western blotting, they reacted with all PA
      preparations tested and no cross-reactivity was observed with lethal factor,
      edema factor of B. anthracis and with other organisms. These MoAbs could detect
      PA from 22 confirmed clinical isolates of B. anthracis on Western blotting and
      hold promise for direct detection of PA in clinical samples for diagnosing
      anthrax.

PMID- 15255604
TI  - Growth-associated production and characterization of poly (3-hydroxybutyric acid)
      of Azotobacter beijerinckii DAR-102.
AB  - Production of poly (3-hydroxybutyric acid) [P(3HB)] by Azotobacter beijerinckii
      DAR-102 isolated in this laboratory has been optimized under batch-culture. The
      accumulatad polymer attained 58% of cell dry mass during mid-stationary phase
      with an yield of 0.58 g/l when grown in nitrogen-free medium. The optimum
      concentration of glucose and fructose for P(3HB) production was 3% (w/v) and 2%
      (w/v) respectively while that of casamino acid and tryptose was 0.1% (w/v).
      Phosphate at a concentration suboptimal for growth and limitation of oxygen in
      the medium favoured P(3HB) accumulation. The production of P(3HB) was maximum
      with an inoculum dose of 4% (v/v). The accumulated polymer was isolated by direct
      chloroform extraction of the dry cell mass and purified by precipitation with
      diethyl ether. The purified polymer has been characterized in terms of its
      solubility properties, melting temperature, and UV-, IR- and NMR-spectroscopic
      analyses.

PMID- 15255605
TI  - Enzymatic and non-enzymatic antioxidants in selected Piper species.
AB  - Piper species, commonly used in diet and traditional medicine were assessed for
      their antioxidant potential. Catalase activity was predominated in Piper longum,
      followed by Piper cubeba, green pepper, Piper brachystachyum and Piper nigrum. P.
      nigrum was richest in glutathione peroxidase and glucose-6-phosphate
      dehydrogenase, green pepper was richest in peroxidase and vitamin C while vitamin
      E was more in P. longum and P. nigrum. P. brachystachyum and P. longum were rich
      sources of vitamin A. All the Piper species had GSH content of around 1 to 2 nM/g
      tissue. The antioxidant components of Piper species constitute a very efficient
      system in scavenging a wide variety of reactive oxygen species. Antioxidant
      potential of Piper species was further confirmed by their ability to curtail in
      vitro lipid peroxidation by around 30-50% with concomitant increase in GSH
      content.

PMID- 15255606
TI  - Simple and economical assay systems for evaluation of phosphinothricin resistant
      transgenics of sorghum, Sorghum bicolor. (L.) Moench., and pearl millet,
      Pennisetum glaucum (L.) R. Br.
AB  - Five simple and rapid methods for evaluation of sorghum and pearl millet
      transgenics resistant to herbicide phosphinothricin (used as selectable marker)
      were studied. For rapid in vitro selection, three assays (establishment of
      sensitivity curves for embryogenic calli, determination of lethal doses for seed
      germination, and a rapid screening of cut young leaves based on the colour change
      of the medium) were established. For rapid screening of transgenic progeny,
      effects of in vivo Basta leaf spray and dip tests were studied at three different
      morphological stages. For all the above assays, LD50, and LD100 values were
      higher for pearl millet than sorghum. However, in both the crops, genotype effect
      was not significant. The assays standardized in the study were found to be
      effective for rapid, economical and mass-scale identification and
      characterization of transgenic plants of sorghum and pearl millet.

PMID- 15255607
TI  - Genetic transformation of Robinia pseudoacacia by Agrobacterium tumefaciens.
AB  - Transgenic Robinia pseudoacacia plants were obtained by Agrobacterium tumefaciens
      mediated gene transfer. Agrobacterium strain LBA4404 harbouring a binary vector
      that contained the chimeric neomycin phosphotransferase II (NPTII) and beta
      glucuronidase (GUS) genes was co-cultivated with hypocotyl segments of in vitro
      raised seedlings of Robinia. Parameters important for high efficiency
      regeneration and transformation rates included type of explant, pre-conditioning
      of explants and appropriate length of co-cultivation period with Agrobacterium. A
      transformation frequency 16.67% was obtained by 48 hr of pre-conditioning
      followed by 48 hr of co-cultivation. Transformed tissue was selected by the
      ability to grow on kanamycin containing medium. Successful regeneration was
      followed after histochemical GUS assay for the detection of transgenic tissue.
      This transformation procedure has the potential to expand the range of genetic
      variation in Robinia.

PMID- 15255608
TI  - In vitro propagation of three commercial cut flower cultivars of Anthurium
      andraeanum Hort.
AB  - In vitro propagation of Anthurium andraeanum Hort. cut flower cultivars viz. Lima
      White, Tropical White and Tropical Red through organogenesis using mature plant
      derived leaf explants was established on Murashige and Skoog (MS) medium
      fortified with different growth regulators. Cultivar, stage and different regions
      of the source leaf, and type of growth regulators significantly influenced callus
      induction. Explants from folded brown leaves were superior in induction of
      callus. Half strength MS medium fortified with 0.88 microM of benzyiadenine (BA),
      0.9 microM of 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.46 microM of kinetin
      (Kn) at pH 5.5 was most effective for callus induction. Transfer of callus to
      medium with 0.54 microM of NAA in place of 2,4-D induced higher number of shoots.
      Subsequent cultures displayed enhanced rate of shoot initiation and
      multiplication. Transfer of shoots onto half strength MS medium supplemented with
      0.54 microM of NAA favoured rooting of shoots. Cultivar Tropical White was
      superior in callus, shoot and root induction compared to Lima White and Tropical
      Red. Plantlets after acclimation in greenhouse were transferred to net-house,
      that exhibited ninety seven per cent survival. Plants flowered normally between
      12 and 15 months and were morphologically similar to that of the mother plants.

PMID- 15255609
TI  - Effect of NaCl on leaf salt secretion and antioxidative enzyme level in roots of
      a mangrove, Aegiceras corniculatum.
AB  - Short-term salt (NaCl) treatment on Aegiceras corniculatum in roots and leaves
      showed no change in fresh and dry weight of leaves, roots and leaf area. There
      was no significant change in total soluble root protein, photosynthetic pigments
      of leaves and spectral characteristics of thylakoids. However, the activity of
      antioxidative enzymes (catalase, ascorbate peroxidase and guaiacol peroxidase) in
      roots decreased by 72, 58 and 80% respectively after 96 hr of treatment (300 mM
      of NaCl). Secretion of salts from the leaf salt glands and salt accumulation on
      upper surface of the leaves were quantified that revealed linear increase of salt
      secretion of leaf with increase in period of salt treatment. It was concluded
      that loss of activities of antioxidative enzymes at high salt treatment, caused
      leaf senescence in spite of high rates of salt secretion by Aegiceras
      corniculatum.

PMID- 15255610
TI  - Macromolecular synthesis in wing discs of Spodoptera mauritia Boisd: effects of a
      juvenile hormone analogue.
AB  - Last instar larvae of S. mauritia treated topically on day 0, day 1, day 2 and
      day 3 with a daily (dose of 25 microg juvenile hormone analogue (JHA) moulted
      into supernumerary larvae. The imaginal discs of the supernumerary larvae
      especially those of mouthparts and thoracic appendages showed pupal
      characteristics. However the wing discs, which showed only partial
      differentiation, were uneverted and highly tanned. In an effort to provide an
      explanation to this anomaly the RNA, DNA and protein profile in the wing discs of
      supernumerary larvae were studied. Quantitative analysis of DNA, RNA and protein
      showed a considerable increase in the amount of DNA and protein and a decline in
      RNA level. SDS-PAGE analysis of wing disc proteins of JHA treated larvae showed a
      reduction in the expression of many major proteins that were predominant in the
      wing discs of control larvae. The results suggest that JHA induced inactivation
      of genes involved in the synthesis of proteins needed for evagination process may
      be responsible for the formation of uneverted, partially differentiated pupal
      wing discs in supernumerary larvae.

PMID- 15255611
TI  - Response related enzymatic changes in ovaries of superovulated mice.
AB  - Adult female mice were superovulated with PMSG followed by HCG and 140
      blastocysts and 69 morulae were recovered from 24 mice. On the basis of the
      response, mice were divided into six groups; non responders, 1-5, 6-10, 11-20, 21
      30 and >30 embryos. The ovaries of the animals were pooled group wise,
      homogenized in PBS (pH 7.4) and after centrifugation for 10-15 minutes, the
      supernatant was analyzed for the enzymes, guanine oxaloacetate transaminase
      (GOT), guanine pymvate transaminase (GPT), acid phosphatases (ACP) and alkaline
      phosphatases (AKP). Acid and alkaline phosphatase activities did not show any
      variation in relation to response to superovulation but GOT and GPT showed
      significantly increased activity in response to induction of superovulation. A
      statistically significant positive correlation was found between GOT and GPT
      activities and the superovulatory response in mice.

PMID- 15255612
TI  - Effect of 24-epibrassinolide on pollen viability during heat-stress in tomato.
AB  - Tomato pollen when treated with 24-epibrassinolide (EBR), it was observed that in
      vitro pollen germination was more tolerant to high temperature. A significantly
      higher in vitro pollen germination, enhanced tube growth and low pollen bursting
      were observed in presence of EBR at 35 degrees C. Since a preconditioning
      treatment of tomato plant was not required for these effects, it is concluded
      that EBR treatment increased basic thermotolerance of germinating pollen. This
      study provided the first evidence for EBR induced thermotolerance in germinating
      pollen.

PMID- 15255613
TI  - Detection of spores of Bacillus anthracis from environment using polymerase chain
      reaction.
AB  - A sensitive PCR based detection of Bacillus anthracis spores from environnment
      was standardized. Specific 1247bp amplicon could be detected with template
      concentration as low as 13 pg. Sensitivity was enhanced to 10 fold by nesting
      with second set of primers, forming 208bp amplicon. Extraction of DNA from spores
      purified from soil samples by aqueous polymer two-phase system followed by
      partial germination and freeze-thaw treatment yielded best results. Soil sample
      spiked with spores (8x10(2)/g of sample) could be detected with this method.

PMID- 15255614
TI  - Effect of methanolic leaf extract of Cissampelos mucronata A. Rich against
      indomethacin induced ulcer in rats.
AB  - Five fractions (F1-F5) isolated from the methanolic leaf extract of Cissampelos
      mucronata A. Rich were investigated for antiulcer activity. At the dose of 450
      mg/kg, they showed varying degree of protection against ulcer induced by
      indomethacin; the order of protection being F1>F4>F5>F2>F3. The antiulcer potency
      of F1 and F2 is comparable with that of cimetidine (100 mg/kg, i.p.). Inhibition
      of gastric mucosal damage may partly contribute to the antiulcer activity of the
      fractions.

PMID- 15255615
TI  - A comment on polemics about the commencement of individual human life.

PMID- 15255616
TI  - Cardiovascular sensory receptors and their regulatory mechanisms.
AB  - The role of cardiovascular receptors in the neural regulation of circulatory
      system is now well established. Atrial type B receptors located in the two atria
      and veno-atrial junctions, which are stimulated by atrial filling are believed to
      play an important role in the regulation of body fluid volume and heart rate.
      Heart rate is influenced also by other sensory receptors e.g. arterial
      baroreceptors, ventricular receptors, pulmonary stretch receptors and
      chemoreceptors. Of all these visceral receptors, arterial baroreceptors located
      mainly in the aortic arch and the carotid sinus region are stimulated by
      intravascular pressure; play a major role in the regulation of blood pressure by
      changes in heart rate and vascular tone. The vascular tone is also affected by
      the circulatory levels of various neurotransmitters and hormones. Vasodilatory
      response to adenosine and acetylcholine is partly mediated through endothelium
      derived relaxing factors (EDRF), hyperpolarizing factors (EDHF) and contracting
      factors (EDCF). The endothelium-dependent mechanisms are altered during
      hypertension and diabetes. The autonomic control of blood pressure is primarily
      through arterial baroreceptors. The sensitivity of the baroreceptor heart rate
      reflex is significantly attenuated on occlusion of left anterior descending
      coronary artery (LAD) of anaesthetised dogs taken as an experimental model of
      coronary insufficiency in-patients of coronary heart disease. The fall in the
      sensitivity of baroreflex on LAD occlusion is mediated primarily by sympathetic
      limb of the autonomic nervous system. Acute fall in hemoglobin level by
      hemodilution in dogs produced an increase in cardiac output by increasing the
      heart rate through inhibition of parasympathetic tone. After parasympathetic
      blockade the increase in cardiac output on fall in hemoglobin was due to a rise
      in the stroke volume. Acute fall in hemoglobin level attenuated the baroreflex
      response. Sustained changes in blood pressure cause resetting of baroreflex i.e.
      increase in arterial pressure involves reduced activity of baroreceptors at
      equivalent pressure and vascular stretch. Like in acute hypoxia the altered
      responsiveness of baroreceptor heart rate reflex during oxygen deficiency due to
      acute occlusion of LAD or acute normovolemic hemodilution may involve both
      peripheral and central components and possibility of modulation by circulating
      hormones also exists.

PMID- 15255617
TI  - mRNA expression pattern of multiple members of connexin gene family in normal and
      abnormal fetal gonads in mouse.
AB  - Gap junctions are made of connexin (Cx) molecules and provide communications
      between adjacent cells through which small molecules (<1kDa) move between
      cytoplasms. The connexin gene family consists of at least 17 members. Gap
      junctions play important roles in ovarian and testicular function. Connexin 43
      (Cx43) knockout mouse is a model for developmentally impaired fetal gonads. The
      aim of the current study was twofold: (a) to analyze mRNA expression pattern of
      multiple members of connexin gene family in normal fetal gonads; (b) to
      investigate any alteration of mRNA expression of connexins in developmentally
      impaired fetal gonads. The study was conducted in normal gonads obtained from
      17.5 dpc wildtype (Cx43+/+) and heterozygote (Cx43+/-) fetuses and in
      developmentally impaired gonads obtained from 17.5 dpc knockout (Cx43-/-)
      fetuses. The mRNA expression pattern of connexins (Cx26, Cx30.3, Cx31, Cx31.1,
      Cx32, Cx37, Cx40, Cx43, Cx45, Cx46 and Cx50) was analyzed by RT-PCR. The mRNA
      transcripts for Cx32 and Cx50 were absent in fetal testis of all the genotypes,
      and the transcripts for Cx26, Cx30.3, Cx31.1, Cx32, Cx40, Cx46 and Cx50 were
      absent in fetal ovary of all the genotypes. The transcripts for Cx43 showed
      expression in Cx43+/+ and Cx43+/- gonads and were absent in Cx43-/- gonads, as
      expected. Additionally, the mRNA transcripts for 8 more connexins (Cx26, Cx30.3,
      Cx31, Cx31.1, Cx37, Cx40, Cx45 and Cx46) showed expression in Cx43+/+ and Cx43+/-
      fetal testes, but the transcripts for only 4 connexins (Cx26, Cx37, Cx40 and
      Cx45) showed expression in Cx43-/- fetal testis. In fetal ovary, the mRNA
      transcripts for 3 more connexins (Cx31, Cx37 and Cx45) were expressed in all the
      genotypes. In summary, from the mRNA expression analysis of 11 members of
      connexin, gene family in 17.5 dpc fetal gonads, besides the expression of Cx43, 8
      additional connexins were expressed in normal fetal testis but only 4 connexins
      were expressed in developmentally impaired testis. The fetal ovary showed the
      expression of 3 additional connexins besides the expression of Cx43. In
      developmentally impaired fetal ovary, only Cx43 was not expressed as expected but
      other three connexins were expresed. The study may be useful in interpreting
      human testis defects in infertility cases.

PMID- 15255618
TI  - Electrophysiologic evaluation of Sudarshan Kriya: an EEG, BAER, P300 study.
AB  - To compare the resting Electroencephalogram (EEG), Brainstem Auditory Evoked
      Responses (BAER) and P300 amongst trained and regular practitioners of Sudarshan
      Kriya (SK) GP-I and Controls (GP-II).

PMID- 15255619
TI  - Correlation of autonomic indices with thyroid status.
AB  - The autonomic status in female thyroid patients was compared with healthy, age
      matched normal females taken as controls. The patients (29 +/- 7 years) were
      categorised into two groups: hyperthyroid and hypothyroid. The valsalva
      manoeuvre, standing to lying ratio (S/L ratio) and immediate heart rate response
      to standing (30:15 ratio) to assess the parasympathetic status while the galvanic
      skin response (GSR) was recorded to assess the sympathetic status. Statistical
      analysis was done using Student's t-test for comparing between the different
      groups and regression analysis were performed between autonomic indices and
      thyroid hormone levels. Although the mean values were not significantly different
      in hypothyroid and hyperthyroid patients, yet the correlation between autonomic
      function and thyroid hormone levels indicates a statistically significant
      difference (P-value<0.05), with the S/L ratio. The correlation was negative for
      log [T3] and log [T4], while it was positive for log [TSH]. This indicates that
      there is decreased parasympathetic activity with increased T3 and T4, which is in
      agreement earlier reports. The GSR, which is one of the measures of sympathetic
      activity, was found to be unaffected.

PMID- 15255620
TI  - Impact of asymptomatic hypertension on left ventricular functions.
AB  - (M-Mode Echocardiography was used to study the L.V. Systolic functions and the
      determinants of L.V. functions in subjects with asymptomatic Hypertension in
      comparison with subjects with normotensives. The functions were assessed among
      (60) sixty healthy subject and sixty (60) hypertensive subjects. The L.V.
      Function Parameters assessed by Echocardiography at lateral and septal sides of
      Left ventricle at the level of mitral annulus. Techholz's formula was used to
      measure the stroke volume, ejection fraction, cardiac output and cardiac index
      etc... The resting stroke volume, cardiac output and cardiac index were normal
      but significantly high among hypertensive subjects compared to normotensive
      subjects (P<0.05). The fractional fiber shortening (F.F.S.) and other parameters
      of L.V. contractile state were significantly reduced among hypertensives compared
      to normotensives (P<0.05). The significant Impairment of F.F.S. is due to
      alteration in dimension of L.V. wall thickness, L.V. cavity, L.V. geometry and
      fibrous changes in L.V. myocardium. This carries prognostic implication and
      requires further documentations, investigations and researches. As the R.A.A.S.
      play role in development of structural changes in L.V. wall drugs A.C.E.
      inhibiters i.e. Captopril and A.II.R. antagonist i.e. Losartan play significant
      role in improvement of L.V. functional changes. Even in the presence of normal
      L.V. systolic function, the L.V. hypertrophy is associated with altered L.V.
      geometry. Normal or near normal F.F.S. is considered a hallmark of normal L.V.
      function when L.V. geometry is normal, but not when L.V. hypertrophy type of
      geometry. Normal limit of F.F.S. should be reset to newer value. The L.V.
      contractile state was negatively correlated to L.V. after load parameters. So the
      main objective of management of hypertensive subjects should be, to reduce the
      after load to improve the L.V. contractile state.)

PMID- 15255621
TI  - Long latency auditory evoked responses in ovulatory and anovulatory menstrual
      cycle.
AB  - Central nervous system pathways get influenced by the changing hormonal levels
      across the menstrual cycle. In an effort to see the effects on the conduction in
      central auditory pathways we recorded long latency auditory evoked potentials
      (LLAEPs) across the 4 different phases of the menstrual cycle. 20 females having
      normal ovulatory menstrual cycles were tested 4 times in a single cycle and
      LLAEPs were recorded from Cz-A1 and Cz-A2 position with alternating 90 dB sound
      pressure click stimuli. Twenty age matched control females having anovulatory
      menstrual cycles were also tested on the corresponding days. All control females
      were taking oral contraceptive (O.C.) pills. The LLAEPs were compared inter-group
      wise as well as inter-phase wise for each parameter by using hierarchal ANOVA
      design and Tukey test was applied to find out the significance level. Peak
      latencies of waves P2 and N2 were found to be delayed during mid-cycle and
      relatively reduced mid-luteal phase in ovulatory menstrual cycles. No such
      response was noticed in oral contraceptive using group. This indicates that
      normal cyclic variations of female sex hormones especially estrogen and
      progesterone modify the central processing of the auditory information. Estrogen
      may be responsible for delaying the conduction by influencing GABA release at the
      level of polysensory association areas of the brain.

PMID- 15255622
TI  - Serum nitrate levels as an index of endothelial function in pre-eclamsia and
      normal pregnancy.
AB  - The study was conducted in St. John's Medical College Hospital and Department of
      Physiology, with the aim of studying the serum nitrate levels in pre-eclampsia
      and normal pregnancy. The total number of subjects studied in various groups were
      159, control (n = 55), first trimester (n = 13), second trimester normal (n =
      42), second trimester pre-eclampsia/PET (n = 5), third trimester normal (n = 32),
      third trimester pre-eclampsia/PET (n = 12). The serum nitrate was measured by one
      step enzymatic assay using Nitrate reductase from Aspergillus species. The
      nitrate levels in the third trimester pre-eclamptic group was found to be
      significant lower (P = 0.02), as compared to normal subjects, however the renal
      functions were normal in all the subjects.

PMID- 15255623
TI  - Changes in glutathione, glutathione-linked enzymes and hexose monophosphate shunt
      enzymes in senile cataract.
AB  - Changes in glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GSH
      R), reduced glutathione (GSH), glutathione peroxidase (GSH-PO), transketolase
      (TK) and transaldolase (TA) were studied in lens and red blood cells (RBCs) to
      understand the possible biochemical mechanisms responsible for the development of
      senile cataract. The activity of G-6-PD was increased in lens, though not so in
      erythrocytes during cataractogenesis. A marked decrease was observed in GSH level
      and GSH-R activity in the lens and RBCs of the cataractous group. The activity of
      GSH-PO was remarkably high in lens but not in the erythrocytes during the
      maturity of cataract. The activity of TK decreased gradually in both the lens and
      erythrocytes. The activity of TA decreased in erythrocytes but increased in the
      lens with maturation of cataract.

PMID- 15255624
TI  - Antioxidant enzymes and peroxidation in galactogenic cataract.
AB  - The antioxidant enzymes like catalase and superoxide dismutase (SOD) were studied
      in erythrocytes and lens at various stages of cataractogenesis in albino rats.
      The rate of peroxidation was measured by assessing the malondiadehyde (MDA) in
      lens and plasma. The insoluble and soluble protein fractions were measured in
      lens to study the protein crosslinkings in relation to the above said parameters.
      Cataract was induced in albino rats by feeding it with 30% galactose as part of
      the normal diet (w/w) for 30 days. The results show a decrease of SOD and
      catalase with concomitant increase of MDA and insoluble protein with the
      advancement of cataract.

PMID- 15255625
TI  - Effect of yoga on cardiovascular system in subjects above 40 years.
AB  - This study was conducted to examine the effect of yoga on cardiovascular function
      in subjects above 40 yrs of age. Pulse rate, systolic and diastolic blood
      pressure and Valsalva ratio were studied in 50 control subjects (not doing any
      type of physical exercise) and 50 study subjects who had been practicing yoga for
      5 years. From the study it was observed that significant reduction in the pulse
      rate occurs in subjects practicing yoga (P<0.001). The difference in the mean
      values of systolic and diastolic blood pressure between study group and control
      group was also statistically significant (P<0.01 and P<0.001 respectively). The
      systolic and diastolic blood pressure showed significant positive correlation
      with age in the study group (r1 systolic= 0.631 and r1 diastolic = 0.610) as well
      as in the control group (r2 systolic = 0.981 and r2 diastolic = 0.864). The
      significance of difference between correlation coefficient of both the groups was
      also tested with the use of Z transformation and the difference was significant
      (Z systolic= 4.041 and Z diastolic= 2.901). Valsalva ratio was also found to be
      significantly higher in yoga practitioners than in controls (P<0.001). Our
      results indicate that yoga reduces the age related deterioration in
      cardiovascular functions.

PMID- 15255626
TI  - Free radical changes in methanol toxicity.
AB  - Role of free radicals in methanol toxicity was evaluated in methanol treated
      albino rats. Methanol intoxication increased lipid peroxidation and depleted the
      free radical scavenging enzyme systems. The free radical quenching effect of
      vitamin E protected the animals from methanol induced free radical damage.

PMID- 15255627
TI  - Simplified [correction of Simlified] calculation of mean QRS vector (mean
      electrical axis of heart) of electrocardiogram.
AB  - In clinical practice assessment of the mean QRS axis (MQRSA) provides information
      related either with hypertrophy of the ventricles or conduction blocks. The
      method adopted by clinicians i.e. the inspection of the QRS voltage in six of the
      limb leads has inherent element of subjectivity of approximately 10degrees.
      Moreover, in certain condition, when there is ambiguity about differentiation of
      left axis deviation assessed by inspection method in to either hypertrophy of
      left ventricles or complete/hemi block of the left bundle branches, accurate
      measurement of the axis becomes necessary to arrive at the correct diagnosis.
      Though a formula based on area under R wave and S-wave of the same QRS complex
      has been derived for accurate measurement of axis, considering its use in the
      computer software, working with ordinary electrocardiograph the only method for
      accurate measurement of the QRS axis is plotting method i. e. the net voltages in
      Lead-I, and III on their respective axes which is not practicable in clinical
      settings. Although, calculation of MQRSA by area method gives an accurate
      assessment of MQRSA, some authors prefer measurement of axis by voltage method,
      as in cases of the right ventricular hypertrophy with a broad S-wave calculation
      of axis by area method may give erroneous results. Hence, to obtain correct
      measurement of MQRSA, we have derived a simplified formula based on the net
      voltage of QRS complexes in Lead-I and Lead-III. The formula derived is as
      follows, Tan(theta) =(I + 2III) divided by sqrt [3I], where I and III represent
      net voltage in Lead-I and III, theta = angle subtended with the axis Lead-I. The
      value of theta can be found by using scientific calculator or the table. In case
      net voltage of QRS complex in Lead-I being negative, the value of the theta
      should be subtracted from 180degrees to find the angle of mean QRS vector.

PMID- 15255628
TI  - Evoked electromyogram as a function of facial nerve.
AB  - Compound muscle action potentials were recorded bilaterally from alae nasi
      muscles following stimulation of facial nerve in 45 normal subjects in the age
      group of 20-30 years. Latency, amplitude and total duration of the compound
      muscle action potential were compared on both sides. A significant positive
      correlation between the three parameters with the highest for the amplitude was
      observed. Therefore it is suggested that amplitude is a better parameter for
      comparison while testing for side to side facial nerve integrity.

PMID- 15255629
TI  - Effect of early luteal phase administration of a single dose mifepristone on
      immunohistochemical distribution of interleukin 1 alpha (IL-1 alpha) and
      transforming growth factor beta 1 (TGF-beta 1) in mid-luteal phase ovary of the
      rhesus monkey.
AB  - A single low dose administration of a high affinity anti-progestin agent like
      mifepristone during the early luteal phase inhibits blastocyst implantation in
      human and non-human primates. Though it has been observed that luteal phase serum
      concentrations of estradiol and progesterone were not affected by the application
      of anti-nidatory dose of early luteal phase mifepristone suggesting that ovarian
      steroidogenic function is not compromised, it is nevertheless possible that
      ovarian physiology at the local tissue level is affected in this treatment
      schedule. In the present study, healthy, mature, proven fertile female rhesus
      monkeys were divided into two groups. Group 2 animals were treated with a single
      dose of mifepristone (2 mg/kg body weight), while group 1 animals were injected
      with vehicle (1:4 benzoyl benzoate: olive oil, v/v, s.c.) on day 2 post
      ovulation. The morphological examination including that of vascularity, as well
      as, histometric determination of profiles of immunopositivity for IL-1alpha and
      TGF-beta1 in stromal, follicular and luteal compartments of mid-luteal phase
      ovaries from animals with or without a single, anti-nidatory dose of mifepristone
      applied on day 2 after ovulation failed to reveal any significant change between
      the two groups. Thus, it appears that early luteal phase administration of a
      single antinidatory dose of mifepristone does not affect the ovarian physiology
      in the treatment cycle.

PMID- 15255630
TI  - Appraisal of abstracts published in volume 45-no.5 supplement-2001 of Indian
      Journal of Physiology and Pharmacology.

PMID- 15255631
TI  - Effect of pranayam on visual and auditory reaction time.

PMID- 15255632
TI  - Effect of inhibitors on glutathione metabolizing enzymes.

PMID- 15255633
TI  - Influence of familial hypertension on blood pressure, serum cholesterol, high
      density lipoprotein cholesterol during second and third decade of life in Punjabi
      population.

PMID- 15255634
TI  - The Nobel Prize in physiology or medicine for the year 2002.

PMID- 15255635
TI  - Chronic administration of caffeine: effect on the activities of hepatic
      antioxidant enzymes of Ehrlich ascites tumor-bearing mice.
AB  - Chronic ingestion (for 22-30 consecutive days) of caffeine (20 mg/kg/day, p.o.)
      increased the activities of the hepatic enzymes- catalase (CAT) and superoxide
      dismutase (SOD) and decreased its lipid peroxidation (LP) in mice. Development of
      Ehrlich ascites carcinoma (EAC) cell decreased the activities of hepatic CAT and
      SOD and increased LP. But pretreatment of caffeine for 12 consecutive days and
      continuation of its treatment during the course of development of EAC cells
      restored the EAC cell-induced changes in liver CAT, SOD and LP to their
      corresponding control values. Thus, the present results by confirming the results
      of others previously published, suggest that caffeine is an antioxidant and may
      act as an anticarcinogen.

PMID- 15255636
TI  - Effect of ascorbic acid on stimulatory status of activated mouse peritoneal
      phagocytes.
AB  - Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid
      have been found to be significantly stimulatory, exhibiting marked alteration at
      the cellular and enzyme levels. Alterations recorded were as follows--cellular
      yield per mouse, their protein content, lysosomal acid hydrolase levels and
      capability to phagocyte, all were significantly enhanced. The new stimulant was
      observed to produce no synergistic action on MPM when thioglycollate, BCG or
      endotoxin along with the same stimulated the latter. Levels of antioxidants like
      ascorbic acid and glutathione were found to be enhanced in elicited macrophages
      whereas superoxide dismutase levels varied when the three above stimulators were
      administered. However, the ascorbic acid elicited cells showed an increase in
      glutathione levels and a decrease in SOD levels but no change in total
      intracellular ascorbic acid levels. Further, though ascorbic acid interaction
      enhanced the phagocytic capability of MPM as compared to resident cells, no
      significant boosting of phagocytic process could be observed when each of three
      stimulators coupled with ascorbic acid was used for macrophage elicitation.

PMID- 15255637
TI  - Mechanism of action of antiatherogenic and related effects of Ficus bengalensis
      Linn. flavonoids in experimental animals.
AB  - One month treatment of alloxan diabetic dogs with a glycoside, viz.
      leucopelargonin derivative (100 mg/kg/day) isolated from the bark of F.
      bengalensis decreased fasting blood sugar and glycosylated haemoglobin by 34% and
      28% respectively. Body weight was maintained in both the treated groups while the
      same was decreased significantly by 10% in the control group. In cholesterol diet
      fed rats, as the atherogenic index and the hepatic bile acid level and the faecal
      excretion of bile acids and neutral sterols increased, the HMGCoA reductase and
      lipogenic enzyme activities in liver and lipoprotien lipase activity in heart and
      adipose tissue and plasma LCAT activity and the incorporation of labelled acetate
      into free and ester cholesterol in liver decreased significantly. On treatment
      with the two ficus flavonoids, viz. leucopelargonin and leucocyanin derivatives
      and another flavonoid quercetin (100 mg/kg/day) the above said effects except on
      bile acids and sterols and lipogenic enzymes were significantly reversed in the
      cholesterol fed rats. However in the treated rats the hepatic level of bile acids
      and the faecal excretion of bile acids and neutral sterols still further
      increased and the action of lipogenic enzyme glucose 6 phosphate dehydrogenase
      was still further decreased. These effects of leucopelargonidin and quercetin
      were better than that of the second. Toxicity studies are required to be carried
      out to find out if the ficus flavonoids could be used as health promoters as they
      are hypocholesterolemic and antioxidant in action.

PMID- 15255638
TI  - Evaluation of Pongamia pinnata root extract on gastric ulcers and mucosal
      offensive and defensive factors in rats.
AB  - Effect of methanolic extract of P. Pinnata roots (PPRM) was studied against
      various experimental gastric ulcer models and offensive and defensive gastric
      mucosal factors in rats. An initial dose-response study using 12.5-50 mg/kg P.
      Pinnata root extract, when given orally in two divided dose for 4 days + 5th full
      dose on the day of experiment 60 min before the experiment, indicated 25 mg/kg as
      an optimal regimen and was used for further study. PPRM showed significant
      protection against aspirin and 4 hr PL, but not against ethanol-induced gastric
      ulceration. It showed tendency to decrease acetic acid-induced ulcer after 10
      days treatment. Ulcer protective effect of PPRM was due to augmentation of
      mucosal defensive factors like mucin secretion, life span of mucosal cells,
      mucosal cell glycoproteins, cell proliferation and prevention of lipid per
      oxidation rather than on the offensive acid-pepsin secretion.

PMID- 15255639
TI  - Effect of ethanol extract of Piper betle Linn leaf on healing of NSAID-induced
      experimental ulcer--a novel role of free radical scavenging action.
AB  - Treatment with ethanol extract of leaf of P. betle at a dose of 150 mg/kg body
      weight daily for 10 days, after induction of peptic ulcer by NSAID in albino
      rats, produced significant healing effect. During healing process, on treatment
      with the extractive, antioxidative factor, e.g. superoxide dismutase and catalase
      activity, mucus and total gastric tissue sulfhydryl group were increased. In
      contrast, oxidised lipid and oxidatively modified proteins were reduced to near
      normalcy, within 7 to 10 days, however, change in the untreated group was not
      significant. The extract also showed significant in vitro free radical scavenging
      action. The results suggest that the antioxidant or free radical scavenging
      activity of the plant extract, may be responsible for its healing action.

PMID- 15255640
TI  - Preliminary studies on acute and subacute toxicity of an antidiabetic herbal
      preparation, Dianex.
AB  - Dianex, a polyherbal formulation intended to use for diabetic patients, has been
      screened for toxic effects. For acute toxicity studies, Dianex was administered
      orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity
      studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered
      orally to the rats once daily for 30 days. Animals were observed for
      physiological and behavioural responses, mortality, food and water intake and
      body weight changes. Hematological evaluation was performed weekly. All the
      animals were sacrificed on 31st day and changes in organ weights and histology
      were examined. Biochemical studies were done in liver and serum. No mortality was
      observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of
      as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in
      gross behaviour, body weight, weight and histology of different organs or serum
      and liver biochemistry. However, significant increase in RBC count and hemoglobin
      level was observed in the treated animals at all doses. Other peripheral blood
      constituents were in the normal range. The dose of Dianex to produce significant
      antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used
      in the present study. Therefore such doses may be safe for daily administration
      without causing any serious side effects.

PMID- 15255641
TI  - Characterisation of fowl adenoviruses from chickens affected with infectious
      hydropericardium during 1994-1998 in India.
AB  - In the present study characterisation has been done for six group I fowl
      adenoviruses (FAV) isolated from outbreaks of infectious hydropericardium (IHP)
      of chickens that occurred in different states/regions of India during the years
      1994-98. These six viruses were identified as FAV serotype 4 by virus
      neutralisation and restriction endonuclease analyses. Antigenic analyses of the
      viruses revealed close relationship (R-values 0.93-0.96). Under the experimental
      conditions, we have been able to induce IHP using FAV serotype 4 isolate AD: 411
      and were also able detect FAV antigens in myocardial tissues by
      immunofluorescence assay (a new observation), an indication that IHP causing FAV
      serotype 4 strain replicate in myocardial tissue. Restriction endonuclease
      analysis of the viral genomes (approximately 46 Kb), using Hind III, Sma I, Xba
      I, Bam HI, Pst I and Dra I produced identical genetic profiles. Pst I and Bam HI
      profiles for these six vitus isolates were identical to those published earlier
      for an IHP causing Pakistani FAV serotype 4 isolate KR31. The identical genetic
      profiles of viruses, chronology of the outbreaks of IHP in Pakistan during 1989
      onward and later in Jammu and Kashmir, India (1994), suggest that FAV serotype 4
      isolates involved in outbreaks of IHP in India had probably spread from Pakistan.
      In order to prevent further spread and economic losses due to IHP in India, based
      on the antigenic relatedness data in this paper, any one of the six studied FAV
      serotype 4 isolates can be used as a candidate for mass production of CEH culture
      based killed vaccine.

PMID- 15255643
TI  - Toxicity of PCB 1232 on mitochondria of fish Arius caelatus (Valenciennes).
AB  - Mitochondrial proteins and phospholipids were estimated and SDH, Na(+)-K(+)
      ATPase and Mg(2+)-ATPase activities were analysed in the gill, liver and heart
      tissues of PCB 1232 (sublethal doses) treated fish A. caelatus. Protein and
      phospholipids were found to be decreased significantly and SDH, Na(+)-K(+)
      ATPase, Mg(2+)-ATPase and other enzyme systems displayed an inverse relationship
      with PCB dosage. Statistical analysis was carried out to indicate the
      relationship between sublethal doses of varying concentration and the activities
      of the enzyme systems involved in energy metabolism. The studies indicated
      impairment in mitochondrial functions.

PMID- 15255642
TI  - Heterochrony in cotton bollworm, Earias vitella (Fb) following ethoxyprecocene
      administration.
AB  - Administration of a synthetic precocene analogue, 7-ethoxy-6-methoxy-2,2-dimethyl
      chromene to fourth and last instar larvae of E. vitella results into
      heterochrony, viz. prothetely and metathetely. These disturbances are due to
      interference with the endocrine system and application of juvenile hormone to
      treated larvae abolishes the effect of ethoxyprecocene.

PMID- 15255644
TI  - Associative diazotrophs of pearl millet (Pennisetum glaucum) from semi arid
      region--isolation and characterization.
AB  - Diversity of the native diazotrophs associated with the rhizosphere of pearl
      millet (P. glaucumn), grown in nutritionally poor soils of semi-arid regions was
      studied with a view to isolate effective nitrogen fixing and plant growth
      stimulating bacteria with root associative characteristics. The native population
      varied from 10(3)-10(4) g(-1) of rhizosphere soil after 40 d growth and belonged
      to genera Azospirillum, Azotobacter and Klebsiella. Another non-diazotrophic root
      associative group was Pseudomonas sp., which also produced IAA and enhanced plant
      growth. Some of these rhizobacteria showed high in vitro acetylene reduction
      activity along with production of indole acetic acid. Out of 11 selected
      diazotrophs used as seed inoculants, M10B (Azospirillum sp.), M11E (Azotobacter
      sp.) and M12D4 (Klebsiella sp.) resulted in significant increase in total root
      and shoot nitrogen at 45 and 60 days of plant growth under pot culture
      conditions.

PMID- 15255645
TI  - Generation and screening of recombinant inbred lines of rice for yellow stemborer
      resistance.
AB  - Based on the results of studies on varietal screening, antixenosis (egg laying
      preference) and antibiosis (larval survival and adult emergence), rice varieties
      W1263 and CO43 were selected as resistant and susceptible parents, respectively,
      for yellow stemborer (YSB) infestation. A mapping population was developed using
      above parents following single seed descent method. Screening for YSB reaction in
      F1 and F2, generations under field and glasshouse conditions for both dead hearts
      and white ears, established the polygenic nature of inheritance for YSB
      resistance. Field screening for YSB resistance at F9 generation revealed the
      difference in the reactions among recombinant inbred lines (RILs) between
      vegetative and reproductive stages. The experiments under field and glasshouse
      screening of RILs for dead hearts showed significant positive association.
      However, the reaction was more towards susceptibility in glasshouse screening due
      to no choice test. Scoring of 250 RILs (F8) for various morphological traits
      showed wide range of variation indicating the suitability for QTL mapping.

PMID- 15255646
TI  - Modulation by phenolic compounds of ABA-induced inhibition of mustard (Brassica
      juncea L. cv. RLM 198) seed germination.
AB  - Exogenous abscisic acid (ABA) inhibited the germination of B. juncea seeds in a
      concentration dependent manner. As revealed in a time-course study, the ABA
      induced inhibition got progressively alleviated with the lapse of time following
      ABA treatment possibly due to metabolic conversion of applied ABA in the seed
      tissue. A simultaneous application of certain phenolic compounds namely, p
      coumaric-, vanillic-, gallic-, and chlorogenic acid (but not caffeic acid) also
      caused an alleviation of ABA effect. Of the above two patterns of recovery, the
      phenolic-dependent alleviation of ABA effect was apparent much earlier (24-48 hr
      treatment) than the time-dependent one (72 hr). It is likely that phenolics could
      accelerate ABA metabolism in the seed tissue leading to an early recovery from
      ABA-induced inhibition.

PMID- 15255647
TI  - Possible role of Granulocyte Macrophage Colony Stimulating Factor receptor (GM
      CSF R) in malaria.
AB  - Malaria has been reportedly increasing in incidence on the globe. Evidence from
      clinical studies supports a role for cytokines in the pathogenesis of cerebral
      malaria. Given the stimulatory effect of the ligand GM-CSF on the synthesis and
      release of the pyrogenic cytokine TNF alpha, the present study has been
      undertaken to investigate a possible role of GMCSF receptor in the pathogenesis
      of both Plasmodium vivax and Plasmodium falciparum malaria. An enzyme immunoassay
      developed by us at our laboratory for the quantitation of GM-CSF receptor has
      been used. No changes in the concentration of the receptor have been indicated
      either at the time of diagnosis or after treatment. In addition, an
      intercomparison of the receptor concentration between the P. vivax and P.
      falciparum groups does not show any significant difference. The results suggest
      that GM-CSF receptor has no significant role in the pathogenesis of either type
      of malaria.

PMID- 15255648
TI  - In vitro efficacy of ciprofloxacin alone and in combination with amoxycillin
      against Salmonella typhi isolates.
AB  - Combined effect of ciprofloxacin (Ci) and amoxycillin (Ax) has been studied in
      vitro against 12 clinical isolates of S. typhi that showed Ci minimum inhibitory
      concentration (MIC) of > or =1 microg/ml. By agar dilution method, MIC values of
      Ax were 10-16 microg/ml for 11 isolates and 0.5 microg/ml for the remaining one
      isolate. The isolates, when treated with Ci and Ax in combination, showed
      fractional inhibitory concentration (FIC) of 0.004-0.256 microg/ml for Ci. FIC of
      Ax ranged from 6-10 microg/ml, except for a single isolate that showed Ax FIC of
      0.25 microg/ml. Thus Ci was more efficacious in combination with Ax against S.
      typhi than Ci alone. The antibiotic combination exhibited an additive effect for
      all the isolates showing FIC index 0.504-0.832.

PMID- 15255650
TI  - Protection of adrenocortical activity by dietary casein in ether anaesthetized
      rats.
AB  - Adrenal delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and
      serum corticosterone level were significantly higher in rats fed with 5% casein
      or 4% albumin diets after 1 hr of ether anaesthetic stress as compared to the
      controls, 5% casein and 20% casein (equivalent to 4% albumin) respectively. Ether
      anaesthesia to 20% casein fed rats caused no change in adrenal delta5-3beta-HSD
      activity and serum corticosterone level when compared with controls fed 20%
      casein diet. The results suggest that high milk protein diet may prevent acute
      stress effects by protecting adrenocortical activity. The present investigation
      opens up a new area of management of stress.

PMID- 15255649
TI  - Antidiarrhoeal effects of methanolic root extract of Hemidesmus indicus (Indian
      sarsaparilla)--an in vitro and in vivo study.
AB  - Methanolic extract of H. indicus root (MHI) was screened for its antimicrobial
      activity against S. typhimurium, E. coli and S. flexneri, in vitro and in
      experimentally induced diarrhoea in albino rats, in vivo. MHI had an anti
      enterobacteriae effect as evident from agar well diffusion method and decrease in
      CFU/ml in MHI treated LB broth culture. MHI inhibited the castor oil induced
      diarrhoea in rats as judged by a decrease in the amount of wet faeces in MHI
      pretreated rats at a dose of 500-1500 mg/kg. The results indicated that MHI was
      more active than standard antidiarrhoeal drug, lomotil. Phytochemical tests
      revealed the main constituents as tannins, steroids, triterpenoids and
      carbohydrates. Present findings suggested that MHI might elicit an antidiarrhoeal
      effect by inhibition of intestinal motility and by its bacteriocidal activity.

PMID- 15255651
TI  - Effect of sodium glycocholate on development of tolerance to Parthenium
      hysterophorus extracts.

PMID- 15255652
TI  - Amylase induction during seed germination in isoproturon susceptible and
      resistant biotypes of Phalaris minor Retz.
AB  - Isoproturon resistant biotype of P. minor germinates early, shows higher
      germination percentage and faster rate of growth as compared to the susceptible
      biotype. Higher amylase activity is observed in the initial hours of imbibition
      in the resistant biotype. In the susceptible biotype it is activated at a much
      later stage.

PMID- 15255653
TI  - Evaluation of entomopathogenic nematode, Steinernema feltiae against field
      population of mustard sawfly, Athalia lugens proxima (Klug) on radish.
AB  - Mustard sawfly, A. lugens proxima, was found to be highly susceptible to
      entomopathogenic nematode, S. feltiae under laboratory condition. Application of
      three different doses of S. feltiae, viz. 1.1 x 10(3), 1.1 x 10(4) and 1.1 x
      10(5) infective juveniles/ml, at weekly intervals, significantly reduced the
      field population of mustard sawfly on radish. The mean larval population of A.
      lugens proxima in all doses of nematode treated plots ranged from 0.42 to 0.48
      larvae per plant as against 2.95 larvae / plant in untreated control plots.
      Similarly, the yield of radish in all the nematode treated plots was
      significantly higher by way of recording 2.80 to 2.87 tons/ha as compared to 1.63
      tons/ha in the case of control.

PMID- 15255655
TI  - Women at AUB: today and yesterday.

PMID- 15255654
TI  - Modified behaviour in nucleopolyhedro virus infected field bean pod borer,
      Adisura atkinsoni and its impact on assessing the field efficacy of NPV.
AB  - When nucleopolyhedro virus of A. atkinsoni was applied at 250 LE/ha, there was no
      significant difference between the viruses treated and control plots with regard
      to the total number of live larvae feeding outside the pod. However, due to
      changes in behaviour in NPV infected A. atkinsoni by way of coming out of the
      pod, there was a significant difference when counts were taken with regard to
      total number of larvae found feeding inside the pod. Both endosulfan at (0.07%)
      and virus (125 LE/ha) in combination with endosulfan (0.035%) significantly
      reduced the larval population of A. atkinsoni and Sphaenarches anisodactylus.
      There was no significant difference between the virus and control plots with
      regard to percentage of pod damage. However, when the yield was assessed based on
      the seed weight, there was significant difference.

PMID- 15255656
TI  - History of anesthesia in Lebanon & at the American University of Beirut.

PMID- 15255657
TI  - Key contributions of two physicians to the development of anesthesia in the
      Republic of Lebanon.

PMID- 15255658
TI  - Revisiting blood transfusion conservation.

PMID- 15255659
TI  - Muscle relaxants for rapid-sequence induction of anesthesia.

PMID- 15255660
TI  - Rapid sequence induction for cesarean section.

PMID- 15255661
TI  - Remifentanil for modulation of hemodynamics in a patient undergoing laparoscopic
      resection of pheochromocytoma.
AB  - The present report monitors the hemodynamic fluctuations in a 63 year-old female
      patient undergoing laparoscopic resection of right adrenal pheochromocytoma
      during remifentanil-based anesthesia. Anesthesia was induced with lidocaine 1 mg
      x kg(-1), propofol 3.5 mg x kg(-1), and cisatracurium 0.2 mg(-1) x kg(-1) and a
      remifentanil infusion was started at a rate of 1 ug.kg (-1) x min(-1). Anesthesia
      was then maintained with remifentanil infusion (0.5 microg(-1) x kg(-1) x min),
      sevoflurane 1-2% (end-tidal) in a mixture of air/oxygen (3:1), and a continuous
      infusion of cisatracurium. There were no significant changes of BP and HR
      following tracheal intubation or surgical incision. However, creation of
      pneumoperitoneum as well as tumor manipulation resulted in a dramatic increase of
      systolic BP and pulmonary artery pressure, associated with a decrease in cardiac
      output. These hemodynamic changes were unresponsive to an increase in the
      remifentanil infusion rate up to 1.5 ug.kg(-1) x min(-1), but were controlled by
      increasing the concentration of sevoflurane up to 6%, and by a nitroglycerin
      (NTG) infusion. Ten min after removal of the tumor, and despite discontinuation
      of the NTG infusion as well as a reduction in the remifentanil infusion and
      sevoflurane concentration, the BP decreased down to 64/43 mmHg. In conclusion,
      the present report shows in a patient undergoing laparoscopic resection of
      adrenal pheochromocytoma that remifentanil does not prevent the severe
      hypertensive episodes associated with intraperitoneal carbon dioxide insufflation
      or tumor manipulation. However, it can be titrated to prevent the hemodynamic
      reflex response to tracheal intubation and surgical stimulation.

PMID- 15255662
TI  - Updates in cardiopulmonary resuscitation: "the new millenium".

PMID- 15255663
TI  - Difficult airway management.

PMID- 15255664
TI  - Obstructive sleep apnea.

PMID- 15255665
TI  - Perioperative management of the patient undergoing vascular surgery.
AB  - Providing optimal perioperative care to the patient undergoing vascular surgery
      is a continuum; it starts with an accurate preoperative identification and
      management of the associated comorbidities, evolves into an adapted selection of
      the level of intraoperative monitoring and the anesthetic technique, and implies
      an extension of the vigilant care into the postoperative period. The
      perioperative consultants, the anesthesiologists, and the surgeons should combine
      their efforts to accomplish this challenging task. Also, they should continuously
      upgrade their skills to cope with the development of new techniques, such as
      endovascular repairs, that may minimize postoperative morbidity.

PMID- 15255666
TI  - Failure to wean from cardiopulmonary bypass.

PMID- 15255667
TI  - Alpha-stat vs. pH-stat strategy during hypothermic cardiopulmonary bypass.
AB  - There are two different strategies of acid-base regulation during hypothermis.
      The alpha-stat strategy of ectotherms maintains the temperature-uncorrected
      arterial PCO2 and pH at normothermic values (i.e., 40 mmHg and 7.4,
      respectively), irrespective of the body temperature. In contrast, the pH-stat of
      hibernators maintains the temperature-corrected pH and PCO2 at the normal values
      at the different body temperatures. Clinically, it appears that it is more
      physiological to use the alpha-stat strategy whenever tepid or moderate
      hypothermic CPB is used in order to maintain intracellular electrochemical
      neutrality, and to adopt the pH-stat strategy whenever deep hypothermic
      circulatory arrest is induced, in order to otimize brain protection.

PMID- 15255668
TI  - Electrical hazards in the operating room.

PMID- 15255669
TI  - Anesthesia for the premature infant.
AB  - The number of infants born prematurely has been increasing over the past few
      years; their survival rate has also been increasing because of the multiple
      advances in health care. The premature infants usually have a number of medical
      problems, asphyxia, ROP, NEC, HMD, BPD, deficient drug metabolism, IVH,
      hematologic derangements, temperature dysregulation, and they present often to
      surgery. The different medical problems associated with prematurity can be
      challenging for the anesthesiologist. Preterm infants require adequate anesthesia
      since they are capable of mounting a stress response otherwise. Preoperative
      evaluation of the medical problems of the infant is essential. Data on anesthetic
      requirements of premature is that few prematures require less anesthesia than
      mature newborns. Anesthesia can be induced with inhaled anesthetic agents but
      these cause hypotension. Thiopental or fentanyl given intravascular can be used
      instead. Fentanyl can be also used for maintenance. Ventilation should be
      manipulated during the operation to accommodate for the change in compliance and
      resistance due to retractors and packs. Fluid losses should be well estimated and
      replaced. Emergence is as dangerous as induction and involves the risk of apnea.

PMID- 15255670
TI  - Postoperative acute renal failure: etiology and preventive strategies.

PMID- 15255671
TI  - Perspectives. Candidates' representatives spar over money, mandates, and more.

PMID- 15255672
TI  - The humoral immune response to head and neck cancer antigens as defined by the
      serological analysis of tumor antigens by recombinant cDNA expression cloning.
AB  - Learning to identify tumor and tumor-associated antigens in patients with
      squamous cell carcinoma of the head and neck (HNSCC) may bring about better
      diagnostic and prognostic evaluations of the disease, innovative therapies based
      on immunological approaches, and a better understanding of the biology of
      tumorigenesis. Serological analysis of tumor antigens by recombinant cDNA
      expression cloning (SEREX) has been used to identify antigens in head and neck
      cancer to which patients have produced high-titered IgG antibodies. Four cDNA
      expression libraries have been screened with sera from 6 head and neck cancer
      patients. Thirty-seven individual gene products were identified. Thirty-one
      previously characterized proteins and 6 genes coding for molecules that are only
      partially characterized or novel were isolated. Tissue expression was evaluated
      by Northern blot analysis, RT-PCR, and in one case, quantitative real-time PCR
      (qPCR) using Taqman technology. Clone AU-HN-15 encoded a protein highly expressed
      in HNSCC tissues and cell lines. Tissue adjacent to the tumor had negligible
      expression. There was low or negligible expression in normal tissues, except for
      the brain and thymus. AU-HN-15 is identical to KIAA0530; it is an uncharacterized
      protein previously cloned from brain tissue and has a zinc finger domain. The
      cDNA encoding this protein has also been isolated in SEREX screens of testicular
      cancer, breast cancer, and colorectal cancer. Whether AU-HN-15 represents a tumor
      antigen target suitable for prognostic or therapeutic purposes is still being
      analyzed.

PMID- 15255673
TI  - Concatenation of two molecular switches via a Fe(II)/Fe(III) couple.
AB  - [reaction: see text] Modulation of the fluorescein fluorescence in the presence
      of spiropyran and ferric ion by light was observed. Such fluorescence modulation
      was due to the low oxidation potential of complex MC.Fe(2+), which made the
      electron transfer from MC.Fe(2+) to Flu(+)()(*)() thermodynamically favorable. As
      a result, the communication between two molecular switches based on fluorescein
      and spiropyan, respectively, was realized via the reversible Fe(III)/Fe(II) redox
      couple. The communicating behavior corresponds well to the function of an INHIBIT
      logic gate.

PMID- 15255674
TI  - Bisfunctionalized Janus molecules.
AB  - [reaction: see text] Bisfunctionalized dendritic multiester molecules were
      synthesized by combined protection-deprotection and divergent-convergent
      divergent sequences in high yields leading to dendritic molecules that combine
      two functionally different surfaces, polar aliphatic arborol and nonpolar gallate
      ether moieties, resulting in a two-faced Janus molecule.

PMID- 15255675
TI  - Using indicator-displacement assays in test strips and to follow reaction
      kinetics.
AB  - [structure: see text] An indicator-displacement assay was used to study the
      kinetics of reactions that produce tartrate. The same assay was also found to be
      useful in developing tartrate test strips, by coating filter paper with the same
      receptor and indicator.

PMID- 15255676
TI  - Concise three-component synthesis of defucogilvocarcin M.
AB  - [reaction: see text] Concise synthesis of defucogilvocarcin M was achieved via
      the [2 + 2 + 2] approach to beta-phenylnaphthalene structure.

PMID- 15255678
TI  - Heck-Suzuki-Miyaura domino reactions involving ynamides. An efficient access to 3
      (arylmethylene)isoindolinones.
AB  - [reaction: see text] Substituted 3-(arylmethylene)isoindolin-1-ones can be
      efficiently synthesized in a stereoselective manner from various ynamides and
      boronic acids by palladium-catalyzed Heck-Suzuki-Miyaura domino reactions.

PMID- 15255677
TI  - Asymmetric synthesis of quaternary alpha- and beta-amino acids and beta-lactams
      via proline-catalyzed mannich reactions with branched aldehyde donors.
AB  - [reaction: see text] L-Proline-catalyzed direct asymmetric Mannich reactions of N
      PMP protected alpha-imino ethyl glyoxylate with various alpha,alpha-disubstituted
      aldehydes affords quaternary beta-formyl alpha-amino acid derivatives with
      excellent yields and enantioselectivities. The Mannich products are further
      converted to the corresponding quaternary alpha- and beta-amino acids and beta
      lactams.

PMID- 15255679
TI  - TiCl4-catalyzed intermolecular hydroamination reactions of norbornene.
AB  - [reaction: see text] An intermolecular hydroamination reaction of norbornene is
      presented that uses catalytic amounts of user-friendly TiCl(4) and tolerates a
      variety of functional groups. In addition, a secondary amine is converted using
      this methodology.

PMID- 15255681
TI  - Novel thiophene oligomers containing a redox active hexaarylethane unit.
AB  - [structure: see text] Novel thiophene oligomers containing a redox active
      hexaarylethane unit have been prepared as a new class of molecular wires having a
      large electrochemical bistability and definitely characterized by using single
      crystal X-ray structure analysis and redox potential measurements. They
      constitute reversible redox pairs with the corresponding bis(thioxanthyl)
      dications by undergoing C-C bond making/breaking. They show unique
      electrochromism and a fluorescence change during interconversion.

PMID- 15255680
TI  - Catalytic hydroamination of alkynes and norbornene with neutral and cationic
      tantalum imido complexes.
AB  - [reaction: see text] Several tantalum imido complexes have been synthesized and
      shown to efficiently catalyze the hydroamination of internal and terminal
      alkynes. An unusual hydroamination/hydroarylation reaction of norbornene
      catalyzed by a highly electrophilic cationic tantalum imido complex is also
      reported. Factors affecting catalyst activity and selectivity are discussed along
      with mechanistic insights gained from stoichiometric reactions.

PMID- 15255682
TI  - Direct asymmetric organocatalytic Michael reactions of alpha,alpha-disubstituted
      aldehydes with beta-nitrostyrenes for the synthesis of quaternary carbon
      containing products.
AB  - [reaction: see text] Direct asymmetric catalytic Michael reactions have been
      performed using chiral-amine/acid bifunctional catalysts. Performed with 0.3
      equiv of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine and 0.3 equiv of
      trifluoroacetic acid as the catalyst, the reaction of alpha,alpha
      dialkylaldehydes with (E)-beta-nitrostyrene provided the alpha,alpha-dialkyl
      Michael products in up to 96% yield with up to 91% ee. With respect to
      enantioselectivity, l-proline was a poor catalyst of this class of Michael
      reactions.

PMID- 15255683
TI  - Synthesis of novel spiro[2.3]hexane carbocyclic nucleosides via enzymatic
      resolution.
AB  - [reaction: see text] Novel R- and S-spiro[2.3]hexane nucleosides have been
      synthesized. The key step involved the Pseudomonas cepacia lipase catalyzed
      resolution of racemic compound 2, synthesized in seven steps starting from
      diethoxyketene and diethyl fumarate, to give (+)-acetate 3 and (-)-alcohol 13.
      (+)-Acetate 3 and (-)-acetate 14 were converted to R- and S-9-(6
      hydroxymethylspiro[2.3]hexane)-4-adenine, respectively.

PMID- 15255684
TI  - Intramolecular iron-mediated diene/olefin cyclocoupling: formation of carbon
      spirocycles.
AB  - [reaction: see text] A short and convenient diastereoselective synthesis of all
      carbon spirocylic molecules was developed. A straightforward protocol that
      involves rearrangement of the diene-Fe(CO)(3) complex followed by cyclization
      delivers the desired product. The reaction substrates were easily prepared by
      reaction of an appropriate nucleophile and a cyclohexadienyl-Fe(CO)(3) cation.

PMID- 15255685
TI  - Double- and triple-consecutive O-insertion into tert-butyl and triarylmethyl
      structures.
AB  - [reaction: see text] The concecutive Criegee rearrangement reactions were studied
      for tert-butyl trifluoroacetate, triarylcarbinols, and benzophenone ketales with
      trifluoroperacetic acid (TFPAA) in trifluoroacetic acid (TFA). The formation of
      methyl acetate and methyl trifluoroacetate indicates that the consecutive double
      O-insertion process has taken place for tert-butyl trifluoroacetate. The
      intermediate dimethoxymethylcarbonium ion was detected below 5 degrees C. A
      consecutive triple-O-insertion process has been observed for triarylmethanols and
      benzophenone ketals. A new high yield method of corresponding diaryl carbonates
      synthesis was developed.

PMID- 15255686
TI  - Callynormine A, a new marine cyclic peptide of a novel class.
AB  - [structure: see text] A novel cyclic peptide, callynormine A, was isolated from
      the Kenyan marine sponge Callyspongia abnormis and its structure elucidated by
      interpretation of its NMR data and X-ray diffraction analysis. Callynormine A
      represents a new class of heterodetic cyclic peptides (designated endiamino
      peptides) possessing an alpha-amido-beta-aminoacrylamide cyclization
      functionality.

PMID- 15255687
TI  - Dendrimers based on a three-dimensionally disposed AB4 monomer.
AB  - [reaction: see text] Design and synthesis of a novel class of dendrons based on
      an AB(4) monomer are described. These dendrons have been evaluated by using
      dendritic encapsulation of a redox active core. The electrochemical properties of
      symmetric ferrocene-cored dendrimers show that significant alterations in redox
      potential and heterogeneous electron-transfer rate constants could be achieved
      even at lower generations.

PMID- 15255688
TI  - Tin(IV) chloride-chiral pyrogallol derivatives as new Lewis acid-assisted chiral
      Bronsted acids for enantioselective polyene cyclization.
AB  - [reaction: see text] New Lewis acid-assisted Bronsted acids (LBAs), tin(IV)
      chloride-2,6-dialkoxyphenols, serve as artificial cyclases for biomimetic polyene
      cyclization. For example, the enantioselective cyclization of 4
      (homogeranyl)toluene using tin(IV) chloride-2,6-di[(1'R,2'R)-trans-2'-(3' ',5' '
      xylyl)cyclohexanoxy]phenol gave a trans-fused tricyclic compound with 85% ee.

PMID- 15255689
TI  - Transient silylation of the guanosine O6 and amino groups facilitates N
      acylation.
AB  - [reaction: see text] The formation of a guanosine derivative silylated at both
      the O6 and amino groups was identified by (15)N NMR. This intermediate allows
      facile reaction with acetyl chloride or phenoxyacetyl chloride to give in high
      yield the corresponding N-protected guanosine derivatives, suitable for use in
      RNA synthesis. The acetyl and phenoxyacetyl amino protecting groups are,
      respectively, 4 and 230 times more labile than the isobutyryl group to
      methylamine/ethanol deprotection.

PMID- 15255690
TI  - Theoretical study on the selectivity of asymmetric sulfur ylide epoxidation
      reaction.
AB  - [structure: see text] We report the first theoretical studies on the asymmetric
      sulfonium ylide epoxidation reaction using a chiral sulfide that successfully
      reproduces the experimentally determined high enantiomeric excess. Calculations
      at the DFT level suggest that the transition states for the addition of the
      sulfonium ylide to benzaldehyde have energies which account for the observed
      enantioselectivity.

PMID- 15255691
TI  - Thiophenol-mediated hydrogen atom abstraction: an efficient tin-free procedure
      for the preparation of cyclopentane derivatives.
AB  - [reaction: see text] An efficient procedure for running a cascade reaction
      involving 1,5-abstraction of a hydrogen atom followed by a radical cyclization is
      reported. Alkenyl radicals are generated from easily available terminal alkynes
      and thiophenol. This procedure eliminates the need of using the toxic tributyltin
      hydride and gives a greater amount of radical translocation products.

PMID- 15255692
TI  - No-D NMR spectroscopy as a convenient method for titering organolithium (RLi),
      RMgX, and LDA solutions.
AB  - [reaction: see text] The concentration of organolithium, organomagnesium halide,
      and lithium diisopropylamide solutions can be reliably determined using No-D NMR
      spectroscopy by integration against the added internal standard 1,5
      cyclooctadiene (COD) (or cyclooctene). In addition, common impurities and
      degradation products can be assessed.

PMID- 15255693
TI  - Stereoselective iodocyclization of 3-acylamino-2-methylene alkanoates: synthesis
      of analogues of N-benzoyl-syn-phenylisoserine.
AB  - [reaction: see text] A convenient approach to racemic analogues of N-benzoyl-syn
      phenylisoserine was realized via the stereoselective iodocyclization of amides
      obtained from Baylis-Hillman adducts.

PMID- 15255694
TI  - Optical resolution and racemization mechanism of a tellurinic acid.
AB  - [reaction: see text] Optically active tellurinic acid was obtained for the first
      time by chromatographic resolution of racemic 2,4,6-triisopropylbenzenetellurinic
      acid (1) using a chiral column. Optically active tellurinic acid (+)-1 was stable
      toward racemization in hexane, although racemization occurred in hexane/2
      propanol. The kinetic studies for the racemization, oxygen exchange reaction
      using H(2)(18)O, and theoretical studies clarified that the racemization of the
      optically active tellurinic acid in solution proceeds via a hypervalent tellurane
      formed by addition of water remaining in solvent.

PMID- 15255695
TI  - Bond dissociation energies for radical dimers derived from highly stabilized
      carbon-centered radicals.
AB  - [reaction: see text] The temperature dependence of the dissociation of dimers
      formed from highly stabilized carbon-centered radicals has been examined.
      Analysis of the data yields the bond dissociation energy (BDE) for the central
      head-to-head C-C bond in these compounds. For example, for the dimer derived from
      3-phenyl-2-coumaranone, BDE is 23.6 kcal/mol and the C-C bond length 1.596 A, a
      rather long value for a sigma bond.

PMID- 15255696
TI  - Efficient acyclic stereocontrol using the tethered aminohydroxylation reaction.
AB  - [reaction: see text] The tethered aminohydroxylation (TA) of acyclic allylic
      carbamates has been achieved in a stereospecific and stereoselective manner.
      Unusually high levels of stereocontrol were observed in the oxidation of 1,1
      disubstituted substrates.

PMID- 15255697
TI  - Short synthesis of the 6,6-spiroketal cores of spirofungins A and B.
AB  - [reaction: see text] Initial efforts toward the total synthesis of the antifungal
      antibiotics spirofungins A and B are reported. A short and efficient synthesis of
      the C9-C20 6,6-spiroketal fragments of both compounds is described. This
      asymmetric approach uses a very efficient alkylation of a lithiated N,N
      dimethylhydrazone followed by spiroketal formation under acidic conditions.

PMID- 15255698
TI  - Chiral shift reagent for amino acids based on resonance-assisted hydrogen
      bonding.
AB  - [structure: see text] A chiral aldehyde that forms resonance-assisted hydrogen
      bonded imines with amino acids has been developed. This hydrogen bond not only
      increases the equilibrium constant for imine formation but also provides a highly
      downfield-shifted NMR singlet for evaluating enantiomeric excess and absolute
      stereochemistry of amino acids.

PMID- 15255699
TI  - Light-driven molecular hinge: a new molecular machine showing a light-intensity
      dependent photoresponse that utilizes the trans-cis isomerization of azobenzene.
AB  - [reaction: see text] A new class of molecular machine exhibits a hingelike motion
      upon photoirradiation. The motion (close and open) can be operated by alternate
      irradiation with UV and visible light. The trans/trans and cis/cis isomers are
      thermally stable at 40 degrees C, and the photochemical closure reaction (from
      trans/trans to cis/cis isomer) is dependent on the intensity of the light used
      because of the short-lived intermediate (trans/cis isomer).

PMID- 15255700
TI  - Diastereoselective mukaiyama and free radical processes for the synthesis of
      polypropionate units.
AB  - [reaction: see text] Reported herein is the synthesis of 8 out of 16
      polypropionates derived from our propionate units. A new strategy involving a
      stereoselective Mukaiyama aldol reaction followed by a stereoselective free
      radical-based hydrogen transfer, both under Lewis acid control, is used. Of
      particular interest is the remarkable reactivity of (i-PrO)TiCl(3) in this
      context to give only the 3,4-anti bromoesters.

PMID- 15255701
TI  - Ruthenium-catalyzed decarboxylative allylation of nonstabilized ketone enolates.
AB  - [reaction: see text] Bipyridyl(pentamethylcyclopentadienyl)ruthenium chloride is
      an efficient catalyst for the formal [3,3] rearrangement of allyl beta
      ketoesters. The mechanism of the transformation involves formation of pi-allyl
      ruthenium intermediates, which are selectively attacked at the more substituted
      allyl terminus by freely diffusing enolates. Decarboxylation of beta
      ketocarboxylates allows generation of enolates under extremely mild conditions.

PMID- 15255702
TI  - Spirastrellolide A: revised structure, progress toward the relative
      configuration, and inhibition of protein phosphatase 2A.
AB  - [structure: see text] The structure of spirastrellolide A, a novel macrolide
      isolated from the marine sponge Spirastrella coccinea, has been revised to
      accommodate new MS and chemical transformation data. Relative configurations of
      three major fragments of the molecule have been elucidated from ROESY and
      coupling constant data. Spirastrellolide A has been shown to be a potent and
      fairly selective inhibitor of protein phosphatase 2A.

PMID- 15255703
TI  - A versatile and stereocontrolled route to pyranose and furanose C-glycosides.
AB  - [reaction: see text] The alpha,beta-unsaturated-gamma,delta-epoxyester 1 is a
      novel and versatile precursor to a wide variety of C-glycosides. For instance,
      treatment of Z-1 or E-1 with palladium(0) affords, stereospecifically, beta- or
      alpha-C-furanosides, respectively. In contrast, reaction of Z-1 or E-1 with base
      gives, stereoselectively, the beta- or alpha-C-pyranosides, respectively.

PMID- 15255704
TI  - New total synthesis of the marine antitumor alkaloid (-)-agelastatin A.
AB  - [reaction: see text] A new total synthesis of (-)-agelastatin A (1) has been
      achieved from the chiral oxazolidinone (-)-3. Although enone transposition was
      problematic when the Michael ring closure of 2 was attempted with strong base,
      the desired cyclization could be effected with Hunig's base after the pyrrole
      nucleus was brominated. Subsequent reduction and monobromination afforded
      synthetic (-)-agelastatin A (1).

PMID- 15255705
TI  - Deacylative oxidation strategy for the preparation of alpha-functionalized
      carbonyls.
AB  - [reaction: see text] alpha-Alkoxylation and amination of carbonyl derivatives is
      made possible through a unique deacylative coupling reaction that proceeds via in
      situ Rh-carbene formation and subsequent heteroatom-H (X-H) insertion. Reactions
      perform optimally with five- and six-membered ring lactone and lactam derivatives
      using both alcohol and carbamate substrates as coupling partners. Substituted
      ethylbenzoyl acetate starting materials have also proven to be effective for this
      oxidative process, affording alpha-functionalized esters under particularly mild
      and operationally facile conditions.

PMID- 15255706
TI  - First isolation of eclipsed vic-disulfoxide: 7,8-dithiabicyclo[4.2.1]nona-2,4
      diene 7-exo,8-exo-dioxide.
AB  - [reaction: see text] The oxidation of 7,8-dithiabicyclo[4.2.1]nona-2,4-diene 7
      exo-oxide with dimethyldioxirane (DMD) provided the 7-exo-8-exo-dioxide, the
      structure of which was determined by X-ray crystallography [S-S 2.341(2) A and 90
      degree angle O-S-S-O 4.1(3) degrees ]. The exo attack of DMD to give the exo,exo
      dioxide was kinetically more favorable than the endo attack to give the endo,exo
      dioxide. DFT calculations showed that the exo,exo-dioxide is thermodynamically
      more stable than the other stereoisomers.

PMID- 15255707
TI  - Solid-phase synthesis and stereochemical assignments of tenuecyclamides A-D
      employing heterocyclic amino acids derived from commercially available Fmoc alpha
      amino acids.
AB  - [reaction: see text] The solid-phase assembly of heterocyclic amino acids enabled
      the total synthesis of numerous diastereoisomers of tenuecyclamides A-D,
      establishing or correcting the stereochemistry of each natural product. This
      strategy provides a very efficient route to synthesize thiazole- and oxazole
      containing macrolactams from heterocyclic amino acids that are readily prepared
      from Fmoc-alpha-amino acids. This methodology appears to be broadly applicable to
      the synthesis of natural product libraries incorporating unnatural heterocyclic
      amino acid residues for the purpose of drug discovery.

PMID- 15255708
TI  - Cu(I)-mediated reductive amination of boronic acids with nitroso aromatics.
AB  - [reaction: see text] A mild method for the reductive amination of aryl boronic
      acids with nitroso aromatic compounds is reported. This C-N bond formation is
      mediated by a stoichiometric amount of CuCl as both a catalyst and a reducing
      agent. Alternatively, 10% Cu(I)-3-methylsalicylate (CuMeSal) catalyzes the same
      reaction in the presence of either ascorbic acid or hydroquinone as the terminal
      reducing agent. Diarylamines bearing a variety of functional groups can be
      obtained in good yields.

PMID- 15255709
TI  - Boron binding with the quorum sensing signal AI-2 and analogues.
AB  - [reaction: see text] The unstable bacterial metabolic product, DPD, and the
      related natural product, laurencione, are shown to have a high affinity for
      borate complexation, through the hydrated analogue. The boron complex of DPD is
      Vibrio harveyi AI-2, an interspecies quorum sensing signal in bacteria, and an
      affinity column with a borate resin is effective in providing the first method
      for concentrating and purifying V. harveyi AI-2 from the biosynthetic product.

PMID- 15255711
TI  - A novel C3v-symmetrical calix[6](aza)cryptand with a remarkably high and
      selective affinity for small ammoniums.
AB  - The three-step synthesis of a calix[6]arene capped with a TAC unit is presented.
      The novel C(3v)-symmetrical calix[6](aza)cryptand displayed an exceptionally high
      affinity for small ammoniums. NMR and X-ray diffraction analyses demonstrated the
      formation of endo-complexes. These complexes are stabilized thanks to (i)
      hydrogen bonding to both the aza cap and one phenolic unit of the calixarene and
      to (ii) cationic and CH-pi interactions between the ammonium and the aromatic
      walls of the host. Combined extraction and competitive binding experiments
      yielded the free energies of bindings DeltaG degrees in chloroform. The values
      are the highest ever obtained with a calixarene-type host. Calix[6]TAC displayed
      the best affinity for EtNH(3)(+). Comparison with other small ammoniums
      emphasizes the high selectivity of the recognition process.

PMID- 15255712
TI  - Origin of enantioselectivity in the Ru(arene)(amino alcohol)-catalyzed transfer
      hydrogenation of ketones.
AB  - The origin of the enantioselectivity in the ruthenium-catalyzed transfer
      hydrogenation has been studied by means of experiment and density functional
      theory calculations. The results clearly show that electrostatic effects are of
      importance, not only in the T-shaped arene-aryl interaction in the favored
      transition state but also between the aryl of the substrate and the amine ligand
      in the disfavored TS. In addition, the electrostatic interaction between the
      alkyl substituent of the substrate and the catalyst is of importance to the
      enantioselectivity. The major cause of enantioselection is found to be of
      nonelectrostatic origin. This inherent property of the catalytic system is
      discussed in terms of dispersion forces and solvent effects. Finally, a minor but
      well-characterized steric effect was identified. The success of this class of
      catalysts in the reduction of alkyl aryl ketones is based on the fact that all
      factors work in the same direction.

PMID- 15255713
TI  - Synthesis of 3 10-helix-inducing constrained analogues of L-proline.
AB  - A bicyclic indolizidinone carboxylic acid and a tricyclic constrained analogue of
      l-proline were synthesized and evaluated for their ability to induce helix
      formation as l-Ala tetrapeptides. Variable-temperature NMR, DMSO titration, CD
      spectra, and X-ray structure analyses, in conjunction with molecular modeling,
      confirmed the existence of 3(10)-helical motifs with di- and tetrapeptides of l
      Ala.

PMID- 15255714
TI  - A new interpretation of chlorine leaving group kinetic isotope effects; a
      theoretical approach.
AB  - The chlorine leaving group kinetic isotope effects (KIEs) for the S(N)2 reactions
      between methyl chloride and a wide range of anionic, neutral, and radical anion
      nucleophiles were calculated in the gas phase and, in several cases, using a
      continuum solvent model. In contrast to the expected linear dependence of the
      chlorine KIEs on the C(alpha)-Cl bond order in the transition state, the KIEs
      fell in a very small range (1.0056-1.0091), even though the C(alpha)-Cl
      transition state bond orders varied widely from approximately 0.32 to 0.78, a
      range from reactant-like to very product-like. This renders chlorine KIEs, and
      possibly other leaving-group KIEs, less useful for studies of reaction mechanisms
      than commonly assumed. A partial explanation for this unexpected relationship
      between the C(alpha)-Cl transition state bond order and the magnitude of the
      chlorine KIE is presented.

PMID- 15255715
TI  - Studies on the synthesis of landomycin A. Synthesis of the originally assigned
      structure of the aglycone, landomycinone, and revision of structure.
AB  - The originally proposed structure (2) of landomycinone, the aglycone of
      landomycin A, has been synthesized and shown to be nonidentical to the naturally
      derived landomycin A aglycone. The synthesis of 2 features the Dotz
      benzannulation reaction of chromium carbene 5 and alkyne 6, and the
      intramolecular Michael-type cyclization reaction of the phenolic naphthoquinone
      20. It is proposed that natural landomycinone possesses the alternative structure
      3, but attempts to access this structure via the Michael-type cyclization of the
      isomeric phenolic naphthoquinone 38 have been unsuccessful.

PMID- 15255716
TI  - Synthesis of pyrroles from 1-dialkylamino-3-phosphoryl(or phosphanyl)allenes
      through 1,5-cyclization of conjugated azomethine ylide intermediates.
AB  - 1-Dialkylamino-1,3-diaryl-3-diphenylphosphanylallenes 3a-e are thermally
      converted into a-annulated 3,5-diarylpyrroles 6a-f and [a]-annulated
      benzo[c]azepines 7a,b,d. These transformations are likely to include conjugated
      azomethine ylide intermediates that can undergo either a 1,5- or a 1,7
      electrocyclization. The periselectivity is markedly shifted toward 1,5
      cyclization when the diphenylphosphanyl substituent is replaced by the
      diphenylphosphoryl group. Thus, 1-dialkylamino-3-(diphenylphosphoryl)allenes 4a-f
      yield pyrroles 6 exclusively and with improved yields, unless the 3-aryl
      substituent in the allene is too electron-rich (e.g., benzodioxol-5-yl, 4f -->
      7f). The preparation and thermal transformation of aminoallenes 4 over three or
      four steps can be conducted as a one-pot procedure, thus providing a convenient
      synthesis of [a]-annulated 3,5-diarylpyrroles from enaminoketones.

PMID- 15255717
TI  - Factors influencing C-ON bond homolysis in alkoxyamines: unexpected behavior of
      SG1 (N-(2-methyl-2-propyl)- N-(1-diethylphosphono-2,2-dimethylpropyl)-N-oxyl)
      based alkoxyamines.
AB  - Alkoxyamines and persistent nitroxides are important regulators of nitroxide
      mediated radical polymerization (NMP). Since the polymerization time decreases
      with the increasing equilibrium constant K (k(d)/k(c)), i.e., the increasing rate
      constant k(d) of the homolysis of the C-ON bond between the polymer chain and the
      nitroxide moiety, the factors influencing the cleavage rate constants are of
      considerable interest. SG1-based alkoxyamines have turned out to be the most
      potent alkoxyamine family to use for NMP of various monomers. Therefore, it is of
      high interest to determine the factors which make SG1 derivatives better
      regulators than TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) derivatives.
      Contrary to what we had observed with TEMPO derivatives, we observed two
      relationships for the plot E(a) vs BDE(C-H), one for the nonpolar released alkyl
      radicals (E(a) (kJ/mol) = -133.0 + 0.72BDE) and the other one for the polar
      released alkyl radicals (E(a) (kJ/mol) = -137.0 + 0.69BDE). However, for both
      families (SG1 and TEMPO derivatives), the rate constants k(d) of the C-ON bond
      homolysis were correlated to the cleavage temperature T(c) (log(k(d)(s(-)(1))) =
      1.51 - 0.058T(c)). Such correlations should help to design new alkoxyamines to
      use as regulators and to improve the tuning of NMP experiments.

PMID- 15255718
TI  - Generation and absolute reactivity of an aryl enol radical cation in solution.
AB  - Laser flash photolysis of 1-bromo-1-(4-methoxyphenyl)acetone in acetonitrile
      leads to the formation of the alpha-acyl 4-methoxybenzyl radical that under
      acidic conditions rapidly protonates to give detectable amounts of the radical
      cation of the enol of 4-methoxyphenylacetone. This enol radical cation is
      relatively long-lived in acidic acetonitrile (tau approximately equal to 200
      micros), which is on the same order of magnitude as the radical cations of other
      4-methoxystyrene derivatives. Rate constants for deprotonation of the radical
      cation and the acid dissociation constant for the enol radical cation were also
      determined using time-resolved absorption spectroscopy. Deprotonation is rapid,
      taking place with a rate constant of 3.9 x 10(6) s(-1), but the enol radical
      cation is found to be only moderately acidic in acetonitrile having a pK(a) =
      3.2. The lifetime of the enol radical cation was also found to be sensitive to
      the presence of oxygen and chloride. The sensitivity toward oxygen is explained
      by oxygen trapping the vinyloxy radical component of the enol radical
      cation/vinyloxy equilibrium, while chloride acts as a nucleophile to trap the
      enol radical cation.

PMID- 15255719
TI  - Rapid and efficient microwave-assisted synthesis of aryl aminobenzophenones using
      Pd-catalyzed amination.
AB  - Substituted aryl aminobenzophenone p38 MAP kinase inhibitors were synthesized in
      good to excellent yields using palladium-catalyzed aryl amination under
      conditions of microwave irradiation. Various ligands have been screened, and the
      reaction conditions were optimized. These coupling reactions are suitable for
      various anilines and aryl bromides that bear a variety of functional groups. Some
      leaving groups (iodides, chlorides, triflates, and tosylates) other than bromides
      have also been investigated. By this method, a large number of aryl
      aminobenzophenone p38 MAP kinase inhibitors were prepared in short order.

PMID- 15255720
TI  - Two complementary approaches toward 2-alkoxy carboxylic acid synthesis from 1,3
      dioxolan-4-ones.
AB  - Two complementary approaches to prepare 2-alkoxy carboxylic acids have been
      developed. Reductive ring opening of various 1,3-dioxolan-4-ones using
      TiCl(4)/Et(3)SiH or (t)BuMgCl affords the desired 2-alkoxy carboxylic acid in
      moderate to excellent chemical yield without loss of optical purity.

PMID- 15255721
TI  - Phototransposition reactions of arylboronate esters in acetonitrile and 2,2,2
      trifluoroethanol.
AB  - The phototransposition (para, meta, ortho) reactions of the arylboronate esters 4
      , 3-, and 2-(4',4',5',5'-tetramethyl-1',3',2'-dioxaborolanyl)toluenes (1, 2, and
      3, respectively) in both acetonitrile and 2,2,2-trifluoroethanol (TFE) using 254
      nm irradiation have been examined. The irradiations resulted in steady-state
      compositions of para (5%), meta (19%), and ortho (76%) isomers in acetonitrile
      starting from the ortho isomer and para (12%), meta (54%), and ortho (35%)
      isomers in TFE starting from the para isomer. Analysis of the (13)C NMR spectrum
      of the product mixture obtained from the photochemistry of the para isomer
      selectively deuterated at C3 and C5 (1d(2)()) revealed that the boron-substituted
      carbon is the active one in the phototransposition reactions in both acetonitrile
      and TFE. Similar results were observed for irradiations of 1 in cyclohexane.
      Fluorescence spectra, singlet-state lifetimes, and Stern-Volmer quenching of
      fluorescence with 2,3-dimethyl-1,3-butadiene indicated that the excited singlet
      states of these three isomers were spectroscopic minima and that the excited
      singlet state was the reactive one for 3 in acetonitrile.

PMID- 15255722
TI  - One-pot regioselective synthesis of nitrophenyloxazolinyl styrene oxides by the
      Darzens reaction of vicarious nucleophilic substitution-formed carbanions of 2
      dichloromethyl-4,4-dimethyloxazoline.
AB  - The vicarious nucleophilic substitution reaction of dichloromethyloxazoline 2
      with nitrobenzene has been investigated. Treatment of 2 with t-BuOK followed by
      the addition of nitrobenzene leads to benzylic carbanions 4 or 9 depending upon
      the solvent used (DMSO, DMF, or THF). Subsequent treatment of 4 or 9 with
      aldehydes, in a Darzens-like reaction, furnishes very good yields of nitrophenyl
      oxazolinyloxiranes 8 and 11. 1,2-Dioxazolinyl-1,2-dinitrophenylethene 7 forms
      quantitatively when carbanion 4 is allowed to warm to room temperature in the
      absence of external electrophiles.

PMID- 15255723
TI  - Stereoselectivity and regioselectivity in nucleophilic ring opening in
      derivatives of 3-phenylisoxazolo[2,3-a]pyrimidine. Unpredicted dimerization and
      ring transformation. Syntheses of derivatives of pyrimidinylmethylamine,
      pyrimidinylmethylamino acid amides, and alpha-amino-2-pyrimidinylacetamides.
AB  - The nucleophilic ring opening of the isoxazolone ring in 2-oxo-3
      phenylisoxazolo[2,3-a]pyrimidine derivatives by optically active amino acid
      amides and ephedrine led to pyrimidinylmethylamino acid amides. Using amides of
      different L-amino acids and (-)-ephedrine resulted in different degrees of
      stereoselectivity. The degree of streoselectivity depended mostly on the
      nucleophile used. When applying hydroxy amines such as ephedrine, the attack via
      the secondary amino group was found as the favored regioselectivity. Upon
      replacement of the oxo group in position 2 in the phenylisoxazolo[2,3
      a]pyrimidine system by an imino group, it was expected that the spontaneous
      decarboxylation that follows the ring opening would not take place, thus
      achieving amino acid amide derivatives of 2-pyrimidinylacetamide, which are
      closely related to pyrimidoblamic acid, an important constituent of Bleomycins,
      used in cancer therapy. However, by heating 5,7-dimethyl-2-imino-3
      phenylisoxazolo[2,3-a]pyrimidine in solution, it underwent an unprecedented
      dimerization process that involved both the phenyl and the imino group. After
      protecting the imino group by acetylation, the ring opening by nucleophiles was
      possible, resulting in the formation of derivatives of 2-pyrimidinylacetamide. 2
      Acetylimino-5,7-dimethyl-3-phenylisoxazolo[2,3-a]pyrimidine also underwent a ring
      transformation, yielding an interesting indolone derivative. Selectivity in ring
      opening and mechanisms of dimerization and ring transformation are discussed.

PMID- 15255724
TI  - Reaction of bromomethylazoles and tosylmethyl isocyanide. A novel
      heterocyclization method for the synthesis of the core of marine alkaloids
      variolins and related azolopyrimidines.
AB  - A novel and efficient synthesis of the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine
      system, the heterocyclic core of the variolin family of marine alkaloids, is
      described. The route involves the reaction of 3-bromo-2-(bromomethyl)pyrrolo[2,3
      b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions.
      This unprecedented reaction was also used to synthesize a series of new
      methoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles,
      bromomethylbenzimidazole, and bromomethylpyrazole. Hydrolysis and decarboxylation
      of 5-bromo-7-methoxycarbonylpyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine obtained by
      this heterocyclization process and installation of the pyrimidine moiety in the
      C5 position open an alternative approach to complete a total synthesis of
      variolin B.

PMID- 15255725
TI  - Virtually complete control of simple and face diastereoselectivity in the Michael
      addition reactions between achiral equivalents of a nucleophilic glycine and (S)-
      or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for
      preparation of beta-substituted pyroglutamic acids and prolines.
AB  - This study demonstrates a new strategy for controlling the stereochemical outcome
      of the Michael addition reactions between nucleophilic glycine equivalents and
      alpha,beta-unsaturated carboxylic acid derivatives: The addition reactions
      between achiral Ni(II)-complex of the Schiff base of glycine with o-[N-alpha
      pycolylamino]acetophenone and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2
      ones were shown to occur at room temperature in the presence of nonchelating
      organic bases and, most notably, with very high stereoselectivity at both newly
      formed stereogenic centers. Thus, the chiral 4-phenyl-1,3-oxazolidin-2-one moiety
      was found to control efficiently both face diastereoselectivities of the glycine
      derived enolate and the C,C double bond of the Michael acceptor. The new strategy
      developed in this work is methodologically superior to previous methods, most
      notably in terms of generality and synthetic efficiency. Excellent chemical
      yields and diastereoselectivities, combined with the simplicity of the
      experimental procedures, render the present method of immediate use for preparing
      various 3-substituted pyroglutamic acids and related amino acids (glutamic acids,
      glutamines, prolines, etc.) available via conventional transformations of the
      former.

PMID- 15255726
TI  - Regioselective aminolysis and hydrolysis of chiral 1,4-ferrocenyl diacetate.
AB  - The treatment of (1R,4R)-1,2-bis(phenylmethyl)ferrocenyl diacetate 2a with
      aqueous ammonium in THF/MeOH at room temperature for 18 h gave the single
      diastereomer of the (1R,4R,Sp)-1,2-acetoamido alcohol 4a with retention of the
      configuration. This result showed that the aminolysis occurred regioselectively
      at one side of the two acetates. Similarly, hydrolysis of the diacetate 2a at
      room temperature for 18 h occurred regio- and stereoselectively to give the
      optically active half-ester 10 in a good yield. The ease of the substitution may
      depend on the geometry of the two stereogenic centers. Only one of the acetoxy
      groups is suitably aligned for ionization (exo to the ferrocenyl group) to
      proceed efficiently; the aminolysis takes place smoothly by iron-assisted
      ionization, i.e., neighboring group participation. The leaving group on the
      second acetoxy group is not suitably aligned (endo to the ferrocenyl group) and
      also cannot undergo a conformational change for it to adopt the appropriate
      orientation for ionization to occur. This reaction is the first case of
      substitution in a chiral molecule in which a conformational difference between
      two leaving groups happened to affect the rate of aminolysis and hydrolysis at
      two stereogenic centers.

PMID- 15255727
TI  - Diastereoselective protonation on radical anions of electron-deficient alkenes
      via photoinduced electron transfer.
AB  - Diastereoselective protonations in the photoinduced electron transfer (PET)
      reactions of 1,1-dicyanoethene derivatives (1a-e) by use of organosilicon
      compounds such as allyltrimethylsilane (2) and benzyltrimethylsilane (5) are
      described. Irradiation of an acetonitrile-acetic acid solution containing 4-tert
      butylcyclohexylidenepropanedinitrile (1a) and an excess of 2 in the presence of
      phenanthrene (Phen) as a sensitizer afforded reduction and allylated products
      (3a, 4a) in 63:37 and 57:43 ratios in a less regioselective manner.
      Photoreactions of 3,3,5-trimethylcyclohexylidenepropanedinitrile (1b), 2
      methylcyclohexylidenepropanedinitrile (1c), bicyclo[2.2.1]-2
      heptylidenepropanedinitrile (1d), and 1,7,7-trimethylbicyclo[2.2.1]-2
      heptylidenepropanedinitrile (1e) with 2 showed higher diastereoselectivity via
      the PET process. Similar diastereoselectivities were obtained in the Phen
      sensitized photoreaction of 1a-e with 5. When 2,4,6-trimethylpyridinium tosylate
      (7) was used as a proton source in place of acetic acid, the product ratios were
      substantially changed in several cases. From these results, steric and torsional
      effects have been postulated as important factors for the control of the
      diastereoselectivity in these PET reactions.

PMID- 15255728
TI  - UV photoelectron spectroscopic study of substituent effects in quinoline
      derivatives.
AB  - The molecular and electronic structure of eight substituted quinolines has been
      investigated by HeI/HeII photoelectron spectroscopy, Green's function
      calculations, and comparison with the spectra of related compounds. The
      correlation between nitrogen lone pair ionization energies and basicity in 18
      substituted quinolines is discussed. The influence of different substituents has
      been quantified via the scheme that is based on experimental energy shifts. The
      relationships between nitrogen ionization energies, pK(a) values, and medicinal
      activity are also discussed.

PMID- 15255729
TI  - Catalytic asymmetric cyclocarbonylation of o-isopropenylphenols: enantioselective
      synthesis of six-membered ring lactones.
AB  - Cyclocarbonylation of o-isopropenylphenols with CO (500 psi) and H(2) (100 psi),
      using Pd(OAc)(2) and (+)-DIOP as the chiral catalyst, in CH(2)Cl(2) affords 3,4
      dihydro-4-methylcoumarins in 60-85% yield and in up to 90% enantiomeric excess.
      The stereoselectivity is influenced by the structure of the chiral phosphine
      ligands and substrates, as well as by the reaction conditions.

PMID- 15255730
TI  - Convergent highly stereoselective preparation of the C12-C24 fragment of
      macrolactin A.
AB  - The convergent synthesis of the C12-C24 fragment (lower part) of macrolactin A is
      described. The adapted strategy allowed building up the lower moiety by the
      assembly of three key intermediates via organometallic addition. One hydroxylic
      stereogenic center was introduced by the application of chiral sulfoxides
      methodology on fragment C19-C24. The preparation of the versatile 1,3-anti diol
      synthon C12-C16 was achieved via opening of chiral epoxide and subsequent
      oxidation to a hydroxy ketone. Finally, reductive elimination of the appropriate
      allylic dibenzoate with Na/Hg introduced directly the C16-C19 (E,E)-diene unit,
      in a highly efficient stereoselective fashion.

PMID- 15255731
TI  - Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their
      utility in the assembly of C-fucosides of biological relevance.
AB  - An efficient synthesis of O-benzylated derivatives of the title sugar aldehydes
      via thiazole addition to tri-O-benzyl-l-fuconolactone followed by highly
      stereoselective deoxygenation of the resulting thiazolylketose and thiazole to
      formyl transformation is described. Wittig olefination of these aldehydes with
      galactopyranose and glucopyranose 6-phosphoranes and reduction of the resulting
      alkenes afforded alpha- and beta-linked (1-->6)-L-C-fucosyl disaccharides,
      namely, beta-L-C-Fuc-(1-->6)-alpha-D-Gal, alpha-L-C-Fuc-(1-->6)-alpha-D-Gal, and
      alpha-L-C-Fuc-(1-->6)-alpha-d-Glc. The alpha-anomer of the above C-fucosyl
      aldehydes was transformed into a C-fucosylmethyl triphenylphosphonium iodide from
      which the corresponding C-fucosylmethylene phosphorane was generated upon
      treatment with BuLi. This phosphorane reacted with the Garner aldehyde (N-Boc D
      serinal acetonide) and its one-carbon higher homologue to give alkenes whose
      reduction and unveiling of the glycinyl group from the oxazolidine ring afforded
      C-fucosyl alpha-amino acids, namely alpha-L-linked C-fucosyl serines and C
      fucosyl asparagines. As a final test of the synthetic utility of the title
      aldehydes, the beta-anomer was employed as starting material in the
      stereoselective synthesis of both R- and S-epimer L-C-fucosyl phenylhydroxy
      acetates. One epimer was obtained by reaction of the sugar aldehyde with
      phenylmagnesium bromide, oxidation of the resulting alcohol to ketone, addition
      of 2-lithiothiazole to the latter, and transformation of the thiazole ring into
      the carboxyl group through an aldehyde intermediate. The other epimer was
      obtained by the same procedure and inverting the timing of phenyl and thiazolyl
      group addition. In both routes, the key step establishing the configuration of
      the quaternary carbon atom of the aliphatic chain was the highly stereoselective
      addition of the organometal to the ketone intermediate.

PMID- 15255732
TI  - Study on photochromic diarylethene with phenolic Schiff base: preparation and
      photochromism of diarylethene with benzoxazole.
AB  - A photochromic diarylethene with phenolic Schiff base 1a can be easily
      transformed to photochromic diarylethene with benzoxazole 3a in the conditions of
      base and phototrigger. Both of their photochromic properties are investigated.
      They show that the conversions of ring-open form to ring-closed form at
      photostationary equilibrium are ca. 20% and 10% for 3a and 1a, respectively, and
      the backconversions are in nearly quantitative yield for both compounds. They
      also show that the response time for photostationary equilibrium is ca. 0.5 and 5
      min for 3a and 1a, respectively, in the solution. In addition, a general
      preparation of 2-arylbenzoxazole from phenolic Schiff base in the conditions of
      base and phototrigger is demonstrated by employing phenolic Schiff bases with
      different substituted groups as template, and other conditions (solvents, in the
      presence and absence of oxygen) for preparation of benzoxazole from phenolic
      Schiff base are explored as well.

PMID- 15255733
TI  - Highly diastereoselective reductive coupling of 2-bromo-2,3,3,3
      tetrafluoropropanamide with aldehydes promoted by triphenylphosphine-titanium(IV)
      isopropoxide. An efficient route to the synthesis of erythro-alpha-fluoro-alpha
      (trifluoromethyl)-beta-hydroxy amides.
AB  - The reductive coupling reaction of N-methoxy-N-methyl-2-bromo-2,3,3,3
      tetrafluoropropanamide (Weinreb amide) with various aldehydes under the influence
      of the combined reagent, 1.2 equiv each of triphenylphosphine and titanium(IV)
      isopropoxide, took place smoothly at ambient temperature to give the
      corresponding alpha-fluoro-alpha-(trifluoromethyl)-beta-hydroxy amides in a
      highly erythro-selective manner. The high erythro selectivity was also obtained
      even by employing a combination of triphenylphosphine (1.2 equiv) and a catalytic
      amount of titanium(IV) isopropoxide.

PMID- 15255734
TI  - Relationship between superelectrophilicity and the electrophilicity index of
      isolated species.
AB  - We report a relationship between the superelectrophilicity of a series of
      dications and the electrophilicity index of isolated species. The enhanced
      electrophilicity is described by global and local reactivity indexes.
      Alkyloxonium and carboxonium dications and diprotonated carboxylic acids have
      been used as simple benchmark systems to discuss this relationship on a
      qualitative and quantitative basis. The theoretical scale of electrophilicity
      roughly reproduces the experimental superelectrophilicity hierarchy established
      on the basis of the (17)O and (13)C NMR chemical shifts in alkyloxonium and
      carboxonium ions and diprotonated carboxylic acids.

PMID- 15255735
TI  - Direct preparation of allylic indium(III) reagents from allylic alcohols via a
      reductive transmetalation of pi-allylnickel(II) with indium(I) iodide.
AB  - InI-mediated direct allylation of carbonyl compounds with allylic alcohols
      proceeded smoothly with catalytic amounts of Ni(acac)(2) and PPh(3) to give the
      corresponding homoallylic alcohols in high yields. Allylindium compounds were
      shown to be the real allylating agents in the present system. Substituted allylic
      alcohols gave branched homoallylic alcohols with syn-selectivity irrespective of
      the geometry of the starting allylic alcohols, whereas high anti-selectivity was
      observed when a bulky substituent is present in the allylic alcohols. The outcome
      of the diastereoselectivity is discussed on the basis of the reaction mechanism,
      comparing with the corresponding Pd-catalyzed version. Another distinct behavior
      between the Ni- and Pd-catalyzed allylation was demonstrated in the reaction of
      hex-1,5-diene-3,4-diol derivatives: the Pd catalyst did not give any coupling
      product, whereas the Ni-catalyzed InI-mediated reaction with benzaldehyde
      afforded the 1:1 and 1:2 adduct diols selectively depending on the reaction
      conditions.

PMID- 15255736
TI  - A new class of chiral P,N-ligands and their application in palladium-catalyzed
      asymmetric allylic substitution reactions.
AB  - An efficient and modular synthesis of a series of chiral nonracemic P,N-ligands
      is reported. The P,N-ligands were prepared from 2-chloro-4-methyl-6,7-dihydro-5H
      [1]pyrindine-7-one and a series of substituted chiral C(2)-symmetric 1,2
      ethanediols (R = Me, i-Pr, and Ph). The ligands were evaluated for use in
      catalytic asymmetric synthesis in the palladium-catalyzed allylic substitution
      reactions of a racemic allylic acetate and dimethyl malonate. In the case of the
      P,N-ligand (R = Ph), the reaction was found to be highly stereoselective (90%
      ee).

PMID- 15255737
TI  - Preparation and properties of phosphaethynes bearing bulky aryl groups with
      electron-donating substituents at the para position.
AB  - Phosphaethynes bearing a 2,6-di-tert-butyl-4-(dimethylamino)phenyl, 2,6-di-tert
      butyl-4-methoxyphenyl, or 2,6-di-tert-butylphenyl group were prepared. A (31)P
      NMR spectroscopic investigation of the chemical shifts indicated that electron
      donating groups at the para position cause shifts to a higher field. Bathochromic
      shifts caused by the electron-donating groups were apparently observed in UV-vis
      spectra. The structure of 2-[2,6-di-tert-butyl-4-(dimethylamino)phenyl]-1
      phosphaethyne was analyzed by X-ray crystallography.

PMID- 15255738
TI  - Grignard reaction with chlorosilanes in THF: a kinetic study.
AB  - Kinetics of the reactions of phenylmagnesium chloride and bromide and
      diphenylmagnesium with chlorosilanes were investigated in tetrahydrofurane (THF)
      and in THF-hydrocarbon mixtures. The reaction in THF is much faster than that in
      diethyl ether. Assuming coordination of magnesium halides with three molecules of
      THF, concentrations of all the species involved in Schlenk equilibrium were
      calculated. In the Grignard reaction, species R(2)Mg and RMgX react competitively
      accompanied by additional reaction paths involving electrophilic catalysis by
      magnesium halide. This conclusion also proved to be valid for the Grignard
      reaction with a ketone and probably can be expanded to any Grignard reaction.
      When Schlenk equilibrium is shifted far to the RMgX species, the catalytic
      pathways are insignificant. Substituents at the silicon center control the rate
      of the reaction through their inductive and steric effects.

PMID- 15255739
TI  - Tuning octopolar NLO chromophores: synthesis and spectroscopic characterization
      of persubstituted 1,3,5-tris(ethynylphenyl)benzenes.
AB  - The synthesis of a series of octopolar 1,3,5-tris(ethynylphenyl)benzenes via
      Sonogashira coupling is described, varying the substituents on both the central
      benzene core as well as the acetylenic periphery. In particular, systems bearing
      an electron-rich core and an electron-poor periphery are obtained that display
      advanced optical properties. The linear (by UV-vis and fluorescence spectroscopy)
      and second-order nonlinear optical properties are studied, the latter by hyper
      Rayleigh scattering (HRS) (Hendrickx, E.; Clays, K.; Persoons, A. Acc. Chem. Res.
      1998, 31, 675-683). The influence of different core and periphery substitution is
      revealed by the optical properties and confirms the possibility of fine-tuning
      those. Because of the presence of (one-photon) fluorescence for all compounds,
      femtosecond hyper-Rayleigh scattering has been applied (Olbrechts, G.; Strobbe,
      R.; Clays, K.; Persoons, A. Rev. Sci. Instrum. 1998, 69, 2233-2241). The
      implementation of the deconvolution in the frequency domain allows for a
      demodulation and a phase shift between immediate (nonlinear) scattering and time
      delayed (multiphoton) fluorescence for high modulation frequencies (Wostyn, K.;
      Binnemans, K.; Clays, K.; Persoons, A. Rev. Sci. Instrum. 2001, 72, 3215-3220).
      In accordance with the linear optical properties, the second-order NLO properties
      can also be tuned by varying the core and peripheric substitutents.

PMID- 15255740
TI  - Palladium complexes of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6
      phosphaadamantane: synthesis, crystal structure and use in the Suzuki and
      Sonogashira reactions and the alpha-arylation of ketones.
AB  - Palladium complexes of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6
      phosphaadamantane were prepared and characterized with Pd[1,3,5,7-tetramethyl
      2,4,8-trioxa-6-phenyl-6-phosphaadamantane](2).dba shown to be an effective
      catalyst for use in the Suzuki and Sonogashira reactions and the alpha-arylation
      of ketones. Couplings using this versatile complex proceeded in excellent yields
      under mild conditions.

PMID- 15255741
TI  - Efficient synthesis of aryl vinyl ethers exploiting 2,4,6
      trivinylcyclotriboroxane as a vinylboronic acid equivalent.
AB  - The synthesis of functionalized aryl vinyl ether derivatives can be readily
      achieved utilizing a room-temperature copper(II) acetate mediated coupling of
      substituted phenols with 2,4,6-trivinylcyclotriboroxane-pyridine complex in the
      presence of a suitable base. The scope of the procedure was demonstrated by the
      generation of an array of substituted aryl vinyl ethers. The reaction was seen to
      be tolerant of a diverse range of functional groups yielding products in high
      isolated yields. We have shown that one role of an amine base in the reaction
      sequence is the in situ generation of an amine coordinated boroxine ring. An X
      ray crystal structure and low temperature (11)B NMR study of 2,4,6
      trivinylcyclotriboroxane-pyridine complex demonstrated the nature of the
      tetracoordinate boron species, which may have a key role to play within the
      reaction sequence.

PMID- 15255742
TI  - 14-helical folding in a cyclobutane-containing beta-tetrapeptide.
AB  - The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane
      and beta-alanine residues is described. NMR experiments both at low temperature
      in CDCl(3) and at 298 K in DMSO-d(6) solutions show the contribution of a strong
      hydrogen bond in the folded major conformation of 5. Temperature coefficients and
      diffusion times point out a hydrogen bond involving the NH proton from the
      cyclobutane residue 1 whereas NOEs manifest the high rigidity of the central
      fragment of the molecule and are compatible with a 14-membered macrocycle.
      Theoretical calculations predict a most stable folded conformation corresponding
      to a 14-helix stabilized by a hydrogen bond between NH(10) in the first residue
      and OC(25) in the third residue. This structure remains unaltered during the
      molecular dynamics simulation at 298 K in chloroform. All these results provide
      evidence for a 14-helical folding and reveal the ability of cis-2
      aminocyclobutane carboxylic acid residues to promote folded conformations when
      incorporated into beta-peptides.

PMID- 15255743
TI  - A theoretical study of the formation of phosphaacetylene by thermolysis of
      triallylphosphine.
AB  - A theoretical study of the decomposition of triallylphosphine into
      phosphaacetylene at the B3LYP/6-311++G(3df,2p) level has shown that the most
      likely mechanism involves two retroene eliminations of propene leading to
      vinylphosphaacetylene. Two mechanisms can account for the formation of HCP from
      vinylphosphaacetylene, either by a 1,2 or a 1,3 hydrogen shift. The first pathway
      was found to be the most favored kinetically. It is quite similar to the pathway
      proposed for the thermal decomposition of vinylacetylene into acetylene in the
      shock tube.

PMID- 15255745
TI  - A novel route to imidoylbenzotriazoles and their application for the synthesis of
      enaminones.
AB  - Reactions of secondary amides 2a-i with 1-chloro-1H-benzotriazole and
      triphenylphosphine give imidoylbenzotriazoles 3a-i. The treatment of 3a,b,e,g
      with silyl enol ethers 5a,b in the presence of potassium tert-butoxide provides a
      new general approach to enaminoketones 6a-h.

PMID- 15255744
TI  - Asymmetric protonation of ketone enolates using chiral beta-hydroxyethers:
      acidity-tuned enantioselectivity.
AB  - New chiral hydroxyethers 1a-f were prepared for asymmetric protonation of achiral
      enolates prepared from prochiral ketones. The enantioselectivity of protonation
      was highly dependent upon the acidity of the chiral alcohols, the highest
      enantioselectivity (90% ee) being achieved with 3,5-dichloro-substituted beta
      hydroxyether 1c. A salt-free enolate generated from trimethylsilyl enol ether 4
      provided product of the highest ee. Unlike other reagents, chloro-substituted
      alcohols provided almost consistent enantioselections throughout the reaction
      temperatures examined (-25 to -98 degrees C). Protonation of other aromatic
      ketones showed selectivity similar to that of 2-methyl-1-tetralone.

PMID- 15255747
TI  - Oxoammonium salts. 9. Oxidative dimerization of polyfunctional primary alcohols
      to esters. An interesting beta oxygen effect.
AB  - The use of the oxidant 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium
      tetrafluoroborate in combination with pyridine for the oxidative, dimeric
      esterification of primary alcohols is described. The ester is the predominant
      product of the reaction with alcohols containing a beta oxygen. In the absence of
      a beta oxygen, the corresponding aldehyde is found in appreciable amounts, but a
      concentration effect can be observed. In the absence of pyridine, little ester is
      formed, and no appreciable reaction takes place with beta-oxygenated compounds.
      Delta lactones have been prepared from diethylene glycol and 2,2'-thiodiethanol,
      without sulfur oxidation.

PMID- 15255746
TI  - A new route to meso-formyl porphyrins.
AB  - Prior syntheses of porphyrins bearing meso-formyl groups have generally employed
      the Vilsmeier formylation of an acid-resistant copper or nickel porphyrin. A new
      approach for the synthesis of free base porphyrins bearing one or two (cis or
      trans) meso-formyl substituents entails the use of a dipyrromethane bearing an
      acetal group at the 5-position, a dipyrromethane-1-carbinol bearing an acetal
      group at the 5-position or carbinol position, or a dipyrromethane-1,9-dicarbinol
      bearing an acetal group at a carbinol position. Treatment of the resulting meso
      acetal-substituted free base porphyrin to gentle acidic hydrolysis yields the
      corresponding meso-formyl porphyrin.

PMID- 15255748
TI  - Direct synthesis of 4-arylpiperidines via palladium/copper(I)-cocatalyzed Negishi
      coupling of a 4-piperidylzinc iodide with aromatic halides and triflates.
AB  - A general procedure for the synthesis of 4-arylpiperidines via the coupling of 4
      (N-BOC-piperidyl)zinc iodide with aryl halides and triflates is presented. The
      reaction requires cocatalysis with both Cl(2)Pd(dppf) and a copper(I) species. An
      improved, safer procedure for the activation of zinc dust is also presented.

PMID- 15255749
TI  - Regio- and stereospecific syntheses of syn- and anti-1,2-imidazolylpropylamines
      from the reaction of 1,1'-carbonyldiimidazole with syn- and anti-1,2-amino
      alcohols.
AB  - The regio- and stereospecific conversion of syn- and anti-1,2-amino alcohols to
      their respective syn- and anti-1,2-imidazolylpropylamines via treatment with 1,1'
      carbonyldiimidazole is described. The rationale behind the regio- and
      stereospecific nature as well as the generality of the reaction is discussed.

PMID- 15255750
TI  - Effect of methoxyl group position on the regioselectivity of ammonia substitution
      reactions involving 3,3'-dichloro-2,2'-binaphthoquinones.
AB  - A series of methoxyl-substituted 3,3'-dichloro-2,2'-binaphthoquinones 2 were
      prepared and evaluated for regioselectivity in ammonia substitution reactions.
      Biquinone 2b underwent regiospecific amination at the unsubstituted
      chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate
      regioselectivity (85:15). Biquinone 2d, however, showed no level of
      regioselectivity demonstrating that the position of the methoxyl group influences
      the regiochemistry. The intramolecular hydrogen bond in biquinone 5 altered the
      regioselectivity. Semiempirical calculations revealed comparatively larger LUMO
      coefficients at the chlorinated carbons that underwent preferential substitution.

PMID- 15255751
TI  - Catalytic route to the synthesis of optically active beta,beta-difluoroglutamic
      acid and beta,beta-difluoroproline derivatives.
AB  - Beta,beta-difluorinated amino acid derivatives were synthesized via Mg(0)
      promoted defluorination of alpha-trifluoromethyl iminoester. Bromination of the
      difluoroenamine afforded the bromodifluoromethyl iminoester in good yield. Pd
      catalyzed asymmetric hydrogenation of the bromodifluoromethyl iminoester and the
      subsequent transformations provided optically active beta,beta-difluoroglutamic
      acid and beta,beta-difluoroproline derivatives.

PMID- 15255752
TI  - Syntheses of core-modified corroles by three different [3 + 1] methodologies.
AB  - Three new methods for syntheses of modified oxa corroles bearing one meso free
      carbon in reasonably good yields are reported. The formation of the meso carbon
      bridge and the direct pyrrole-pyrrole linkage occur in a single step by a simple
      condensation and coupling with TFA as a catalyst with appropriate precursors. The
      reactions are optimized with different conditions by varying the meso
      substituents, acid catalyst concentration, and the nature of the solvent to
      afford corroles in good yields.

PMID- 15255753
TI  - Synthesis of cyclic alkenyl ethers via intramolecular cyclization of O
      alkynylbenzaldehydes. Importance of combination between CuI catalyst and DMF.
AB  - An efficient and remarkably general method for the synthesis of cyclic alkenyl
      ethers via the Cu(I)-catalyzed intramolecular cyclization of O
      alkynylbenzaldehydes has been developed. The survey of metal catalysts and
      solvents revealed that the combination of copper(I) iodide and DMF was the
      catalytic system of choice. The reaction most probably proceeds via the
      nucleophilic addition of alcohols 2 to O-alkynylbenzaldehydes 1 to generate the
      corresponding hemiacetals, and subsequent nucleophilic attack of the hemiacetal
      oxygen to the copper coordinated alkyne would give the annulation products 3. In
      all cases, the reaction proceeded in a regiospecific manner leading to the six
      membered endocyclic products via 6-endo-dig cyclization.

PMID- 15255754
TI  - Microwave-assisted group-transfer cyclization of organotellurium compounds.
AB  - Primary- and secondary-alkyl aryl tellurides, prepared by arenetellurolate ring
      opening of epoxides/ O-allylation, were found to undergo rapid (3-10 min) group
      transfer cyclization to afford tetrahydrofuran derivatives in 60-74% yield when
      heated in a microwave cavity at 250 degrees C in ethylene glycol or at 180
      degrees C in water. To go to completion, similar transformations had previously
      required extended photolysis in refluxing benzene containing a substantial amount
      of hexabutylditin. The only drawback of the microwave-assisted process was the
      loss in diastereoselectivity which is a consequence of the higher reaction
      temperature. Substitution in the Te-aryl moiety of the secondary-alkyl aryl
      tellurides (4-OMe, 4-H, 4-CF(3)) did not affect the outcome of the group-transfer
      reaction in ethylene glycol. However, at lower temperature, using water as a
      solvent, the CF(3) derivative failed to react. The microwave-assisted group
      transfer cyclization was extended to benzylic but not to primary- and secondary
      alkyl phenyl selenides.

PMID- 15255755
TI  - 10-hydroxy-10,9-boroxarophenanthrenes: versatile synthetic intermediates to 3,4
      benzocoumarins and triaryls.
AB  - 10-Hydroxy-10,9-boroxarophenanthrenes were obtained as unexpected major products
      upon BBr(3)-mediated O-demethylation of 2-methoxybiaryls. The formation likely
      proceeds via intramolecular electrophilic aromatic cyclization of a reactive
      dibromoaryloxyborane intermediate. Essentially quantitative yields of 10-hydroxy
      10,9-boroxarophenanthrenes were also obtained from 2-hydroxybiaryl and
      BCl(3)/AlCl(3) with use of a modified literature procedure. As synthetic
      intermediates, 10-hydroxy-10,9-boroxarophenanthrenes were efficiently converted
      to 3,4-benzocoumarins and triaryls through Pd-catalyzed CO insertion and Suzuki
      reaction.

PMID- 15255756
TI  - Synthesis of chiral 13C,77Se-labeled selones.
AB  - Stable isotope-labeled N-acyl selones have been constructed in fewer than four
      steps from readily available starting materials. Site-specific labeling was
      achieved using the following synthons: bromo[2-(13)C]acetic acid, [(13)C]formic
      acid, and elemental (77)Se. These labeled selones have been found to provide
      unique insights into enolate structure and may be useful in the detection and
      quantitation of remotely disposed chiral centers in compounds in short supply.

PMID- 15255757
TI  - DMSO/N2H4.H2O/I2/H2O/CH3CN: a new system for selective oxidation of alcohols in
      hydrated media.
AB  - A new alternative system for the oxidation of secondary alcohols to ketones with
      DMSO/N2H4.H2O/I2/H2O/CH3CN in hydrated media has been developed. The system also
      selectively oxidizes the secondary alcoholic groups to the corresponding ketones
      in the presence of primary alcoholic groups present within the same molecule in
      moderate to very good yields at reflux temperature.

PMID- 15255758
TI  - Unique hydrogen bonds between 9-anthracenyl hydrogen and anions.
AB  - Unique hydrogen bonds of the 9-H of anthracene moieties in hosts 1 and 2 with
      fluoride and pyrophosphate ions were observed on the basis of the (1)H NMR
      experiments. Furthermore, hosts 1 and 2 act as a colorimetric sensor and a
      fluorescent chemosensor for the recognition of fluoride ion, respectively.

PMID- 15255760
TI  - The National Institute of Biomedical Imaging and Bioengineering.

PMID- 15255761
TI  - Tissue engineering applications of therapeutic cloning.
AB  - Few treatment options are available for patients suffering from diseased and
      injured organs because of a severe shortage of donor organs available for
      transplantation. Therapeutic cloning, where the nucleus from a donor cell is
      transferred into an enucleated oocyte in order to extract pluripotent embryonic
      stem cells, offers a potentially limitless source of cells for replacement
      therapy. Scientists in the field of tissue engineering apply the principles of
      cell transplantation, material science, and engineering to construct biological
      substitutes that will restore and maintain normal function in diseased and
      injured tissues. The present chapter reviews recent advances that have occurred
      in therapeutic cloning and tissue engineering and describes applications of these
      new technologies that may offer novel therapies for patients with end-stage organ
      failure.

PMID- 15255762
TI  - Biomaterials: where we have been and where we are going.
AB  - Since its inception just over a half century ago, the field of biomaterials has
      seen a consistent growth with a steady introduction of new ideas and productive
      branches. This review describes where we have been, the state of the art today,
      and where we might be in 10 or 20 years. Herein, we highlight some of the latest
      advancements in biomaterials that aim to control biological responses and
      ultimately heal. This new generation of biomaterials includes surface
      modification of materials to overcome nonspecific protein adsorption in vivo,
      precision immobilization of signaling groups on surfaces, development of
      synthetic materials with controlled properties for drug and cell carriers,
      biologically inspired materials that mimic natural processes, and design of
      sophisticated three-dimensional (3-D) architectures to produce well-defined
      patterns for diagnostics, e.g., biological microelectromechanical systems
      (bioMEMs), and tissue engineering.

PMID- 15255763
TI  - Tissue growth and remodeling.
AB  - The growth and remodeling of a tissue depends on certain features in the history
      of its mechanical environment as well as its genetic makeup. The mechanical
      environment influences the tissue's developing morphology, the process of simply
      increasing the size of existing morphological structures, and the formation of
      the proteins of which the tissue is constructed. The relationships between
      genetic information, various epigenetic mechanisms and tissue development are
      discussed. The developmental growth and remodeling of most structural tissues are
      enhanced by the use of those tissues and retarded by their disuse. The mechanical
      or mathematical modeling of tissue growth and development using cellular automata
      models and continuum mechanical models is reviewed.

PMID- 15255764
TI  - Breast tissue engineering.
AB  - Tissue engineering has the potential to redefine rehabilitation for the breast
      cancer patient by providing a translatable strategy that restores the
      postmastectomy breast mound while concomitantly obviating limitations realized
      with contemporary reconstructive surgery procedures. The engineering design goal
      is to provide a sufficient volume of viable fat tissue based on a patient's own
      cells such that deficits in breast volume can be abrogated. To be sure, adipose
      tissue engineering is in its infancy, but tremendous strides have been made.
      Numerous studies attest to the feasibility of adipose tissue engineering. The
      field is now poised to challenge barriers to clinical translation that are
      germane to most tissue engineering applications, namely scale-up, large animal
      model development, and vascularization. The innovative and rapid progress of
      adipose engineering to date, as well as opportunities for its future growth, is
      presented.

PMID- 15255765
TI  - Tissue engineering of ligaments.
AB  - Tissue engineering is emerging as a significant clinical option to address tissue
      and organ failure by implanting biological substitutes for the compromised
      tissues. As compared to the transplantation of cells alone, engineered tissues
      offer the potential advantage of immediate functionality. Engineered tissues can
      also serve as physiologically relevant models for controlled studies of cells and
      tissues designed to distinguish the effects of specific signals from the complex
      milieu of factors present in vivo. A high number of ligament failures and the
      lack of adequate options to fully restore joint functions have prompted the need
      to develop new tissue engineering strategies. We discuss the requirements for
      ligament reconstruction, the available treatment options and their limitations,
      and then focus on the tissue engineering of ligaments. One representative tissue
      engineering system involving the integrated use of adult human stem cells, custom
      designed scaffolds, and advanced bioreactors with dynamic loading is described.

PMID- 15255766
TI  - Advances in high-field magnetic resonance imaging.
AB  - Among advances in magnetic resonance imaging (MRI), the increase of the magnetic
      field strength is perhaps one of the most significant. The use of high magnetic
      fields for in vivo magnetic resonance is motivated by a number of considerations.
      Advantages are increases in signal-to-noise ratio, blood-oxygenation level
      dependent contrast, and spectral resolution, while disadvantages include
      potential reduction of contrast in anatomic imaging owing to lengthening of T1
      and effects of susceptibility of high fields. To address these challenges,
      technical advances have been made in various aspects of MRI, allowing high-field
      MRI to provide exquisite morphological and functional details in clinical and
      research settings. This review provides an overview of technical issues and
      applications of high-field MRI.

PMID- 15255767
TI  - Micro-computed tomography-current status and developments.
AB  - The recent rapid increase in interest in tomographic imaging of small animals and
      of human (and large animal) organ biopsies is driven largely by drug discovery,
      cancer detection/monitoring, phenotype identification and/or characterization,
      and development of disease detection methods and monitoring efficacies of drugs
      in disease treatment. In biomedical applications, micro-computed tomography (CT)
      scanners can function as scaled-down (i.e., mini) clinical CT scanners that
      provide a three-dimensional (3-D) image of most, if not the entire, torso of a
      mouse at image resolution (50-100 microm) scaled proportional to that of a human
      CT image. Micro-CT scanners, on the other hand, image specimens the size of
      intact rodent organs at spatial resolutions from cellular (20 microm) down to
      subcellular dimensions (e.g., 1 microm) and fill the resolution-hiatus between
      microscope imaging, which resolves individual cells in thin sections of tissue,
      and mini-CT imaging of intact volumes.

PMID- 15255768
TI  - Optical projection tomography.
AB  - Optical projection tomography is a new approach for three-dimensional (3-D)
      imaging of small biological specimens. It fills an imaging gap between MRI and
      confocal microscopy, being most suited to specimens that are from 1 to 10 mm
      across. The tomographic principles of optical projection tomography (OPT) are
      explained, its most important applications in biomedical research explored, and
      comparisons drawn of its pros and cons compared to a number of alternative
      imaging technologies.

PMID- 15255769
TI  - Mechanical bioeffects of ultrasound.
AB  - Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool.
      Through both thermal and nonthermal mechanisms, ultrasound can produce a variety
      of biological effects in tissues in vitro and in vivo. This chapter provides an
      overview of the fundamentals of key nonthermal mechanisms for the interaction of
      ultrasound with biological tissues. Several categories of mechanical bioeffects
      of ultrasound are then reviewed to provide insight on the range of ultrasound
      bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the
      potential application of mechanical bioeffects to the design of new therapeutic
      applications of ultrasound in medicine.

PMID- 15255770
TI  - Ocular biomechanics and biotransport.
AB  - The eye transduces light, and we usually do not think of it as a biomechanical
      structure. Yet it is actually a pressurized, thick-walled shell that has an
      internal and external musculature, a remarkably complex internal vascular system,
      dedicated fluid production and drainage tissues, and a variety of specialized
      fluid and solute transport systems. Biomechanics is particularly involved in
      accommodation (focusing near and far), as well as in common disorders such as
      glaucoma, macular degeneration, myopia, and presbyopia. In this review, we give a
      (necessarily brief) overview of many of the interesting biomechanical aspects of
      the eye, concluding with a list of open problems.

PMID- 15255771
TI  - Mechanotransduction at cell-matrix and cell-cell contacts.
AB  - Mechanical forces play an important role in the organization, growth, maturation,
      and function of living tissues. At the cellular level, many of the biological
      responses to external forces originate at two types of specialized microscale
      structures: focal adhesions that link cells to their surrounding extracellular
      matrix and adherens junctions that link adjacent cells. Transmission of forces
      from outside the cell through cell-matrix and cell-cell contacts appears to
      control the maturation or disassembly of these adhesions and initiates
      intracellular signaling cascades that ultimately alter many cellular behaviors.
      In response to externally applied forces, cells actively rearrange the
      organization and contractile activity of the cytoskeleton and redistribute their
      intracellular forces. Recent studies suggest that the localized concentration of
      these cytoskeletal tensions at adhesions is also a major mediator of mechanical
      signaling. This review summarizes the role of mechanical forces in the formation,
      stabilization, and dissociation of focal adhesions and adherens junctions and
      outlines how integration of signals from these adhesions over the entire cell
      body affects how a cell responds to its mechanical environment. This review also
      describes advanced optical, lithographic, and computational techniques for the
      study of mechanotransduction.

PMID- 15255772
TI  - Functional efficacy of tendon repair processes.
AB  - Despite various attempts to repair and replace injured tendon, an understanding
      of the repair processes and a systematic approach to achieving functional
      efficacy remain elusive. In this review the epidemiology of tendon injury and
      repair is first examined. Using a traditional paradigm for repair assessment, the
      biology and biomechanics of normal tendon, natural healing, and repair are then
      explored. New treatment strategies such as functional tissue engineering are
      discussed, including a functional approach to treatment that involves the
      development of in vivo functional design parameters to judge the acceptability of
      a repair outcome. The paper concludes with future directions.

PMID- 15255773
TI  - Fluid mechanics of heart valves.
AB  - Valvular heart disease is a life-threatening disease that afflicts millions of
      people worldwide and leads to approximately 250,000 valve repairs and/or
      replacements each year. Malfunction of a native valve impairs its efficient fluid
      mechanic/hemodynamic performance. Artificial heart valves have been used since
      1960 to replace diseased native valves and have saved millions of lives.
      Unfortunately, despite four decades of use, these devices are less than ideal and
      lead to many complications. Many of these complications/problems are directly
      related to the fluid mechanics associated with the various mechanical and
      bioprosthetic valve designs. This review focuses on the state-of-the-art
      experimental and computational fluid mechanics of native and prosthetic heart
      valves in current clinical use. The fluid dynamic performance characteristics of
      caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial
      stented and nonstented bioprostheic valves are reviewed. Other issues related to
      heart valve performance, such as biomaterials, solid mechanics, tissue mechanics,
      and durability, are not addressed in this review.

PMID- 15255774
TI  - Molecular machines.
AB  - Molecular machines are tiny energy conversion devices on the molecular-size
      scale. Whether naturally occurring or synthetic, these machines are generally
      more efficient than their macroscale counterparts. They have their own
      mechanochemistry, dynamics, workspace, and usability and are composed of nature's
      building blocks: namely proteins, DNA, and other compounds, built atom by atom.
      With modern scientific capabilities it has become possible to create synthetic
      molecular devices and interface them with each other. Countless such machines
      exist in nature, and it is possible to build artificial ones by mimicking nature.
      Here we review some of the known molecular machines, their structures, features,
      and characteristics. We also look at certain devices in their early development
      stages, as well as their future applications and challenges.

PMID- 15255775
TI  - Engineering synthetic vectors for improved DNA delivery: insights from
      intracellular pathways.
AB  - Significant progress has been made in the area of nonviral gene delivery to date.
      Yet, synthetic vectors remain less efficient by orders of magnitude than their
      viral counterparts. Research continues toward unraveling and overcoming various
      barriers to the efficient delivery of DNA, whether in plasmid form encoding a
      gene or as an oligonucleotide for the selective inhibition of target gene
      expression. Novel components for overcoming these hurdles are continually being
      incorporated into the design of synthetic vectors, leading to increasingly more
      virus-like particles. Despite these advances, general principles defining the
      design of synthetic vectors are yet to be developed fully. A more quantitative
      analysis of the cellular uptake and intracellular processing of these vectors is
      required for the rational manipulation of vector design. Mathematical frameworks
      with a more conceptual basis will help obtain an integrated perspective on these
      complex systems. In this review, we critically examine the progress made toward
      the improved design of synthetic vectors by the strategic exploitation of
      intracellular mechanisms and explore newer possibilities to overcome obstacles in
      the practical realization of this field.

PMID- 15255776
TI  - Fractal analysis of the vascular tree in the human retina.
AB  - The retinal circulation of the normal human retinal vasculature is statistically
      self-similar and fractal. Studies from several groups present strong evidence
      that the fractal dimension of the blood vessels in the normal human retina is
      approximately 1.7. This is the same fractal dimension that is found for a
      diffusion-limited growth process, and it may have implications for the
      embryological development of the retinal vascular system. The methods of
      determining the fractal dimension for branching trees are reviewed together with
      proposed models for the optimal formation (Murray Principle) of the branching
      vascular tree in the human retina and the branching pattern of the human
      bronchial tree. The limitations of fractal analysis of branching biological
      structures are evaluated. Understanding the design principles of branching
      vascular systems and the human bronchial tree may find applications in tissue and
      organ engineering, i.e., bioartificial organs for both liver and kidney.

PMID- 15255777
TI  - Advances in quantitative electroencephalogram analysis methods.
AB  - Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based
      clinical diagnosis and studies of brain function. In past decades, various qEEG
      methods have been extensively studied. This article provides a detailed review of
      the advances in this field. qEEG methods are generally classified into linear and
      nonlinear approaches. The traditional qEEG approach is based on spectrum
      analysis, which hypothesizes that the EEG is a stationary process. EEG signals
      are nonstationary and nonlinear, especially in some pathological conditions.
      Various time-frequency representations and time-dependent measures have been
      proposed to address those transient and irregular events in EEG. With regard to
      the nonlinearity of EEG, higher order statistics and chaotic measures have been
      put forward. In characterizing the interactions across the cerebral cortex, an
      information theory-based measure such as mutual information is applied. To
      improve the spatial resolution, qEEG analysis has also been combined with medical
      imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a
      very important role in basic research and clinical studies of brain injury,
      neurological disorders, epilepsy, sleep studies and consciousness, and brain
      function.

PMID- 15255778
TI  - Robotics, motor learning, and neurologic recovery.
AB  - Robotic devices are helping shed light on human motor control in health and
      injury. By using robots to apply novel force fields to the arm, investigators are
      gaining insight into how the nervous system models its external dynamic
      environment. The nervous system builds internal models gradually by experience
      and uses them in combination with impedance and feedback control strategies.
      Internal models are robust to environmental and neural noise, generalized across
      space, implemented in multiple brain regions, and developed in childhood. Robots
      are also being used to assist in repetitive movement practice following
      neurologic injury, providing insight into movement recovery. Robots can
      haptically assess sensorimotor performance, administer training, quantify amount
      of training, and improve motor recovery. In addition to providing insight into
      motor control, robotic paradigms may eventually enhance motor learning and
      rehabilitation beyond the levels possible with conventional training techniques.

PMID- 15255779
TI  - Substrate specificity of Helicobacter pylori histone-like HU protein is
      determined by insufficient stabilization of DNA flexure points.
AB  - The histone-like HU protein is ubiquitous in the eubacteria. A role for
      Escherichia coli HU in compaction of the bacterial genome has been reported,
      along with regulatory roles in DNA replication, transposition, repair and
      transcription. We show here that HU from the human pathogen Helicobacter pylori,
      which has been implicated in the development of ulcers and gastric cancer,
      exhibits enhanced thermal stability and distinct DNA substrate specificity.
      Thermal denaturation of HpyHU (H. pylori HU) measured by CD spectroscopy yields a
      melting temperature (T(m)) of 56.4+/-0.1 degrees C. HpyHU binds linear duplex DNA
      with a site size of approximately 19 bp and with low affinity, but in striking
      contrast to E. coli HU, HpyHU has only modest preference for DNA with mismatches,
      nicks or gaps. Instead, HpyHU binds stably to four-way DNA junctions with half
      maximal saturation of 5 nM. Substitution of two residues adjacent to the DNA
      intercalating prolines attenuates both the preference for flexible DNA and the
      ability to bend and supercoil DNA. These observations suggest that proline
      intercalation generates hinges that must be stabilized by adjacent residues;
      insufficient stabilization leads to reduced bending and a failure to bind
      preferably to DNA with flexure points, such as gaps and mismatches.

PMID- 15255780
TI  - Purified recombinant human prosaposin forms oligomers that bind procathepsin D
      and affect its autoactivation.
AB  - Before delivery to endosomes, portions of proCD (procathepsin D) and proSAP
      (prosaposin) are assembled into complexes. We demonstrate that such complexes are
      also present in secretions of cultured cells. To study the formation and
      properties of the complexes, we purified proCD and proSAP from culture media of
      Spodoptera frugiperda cells that were infected with baculoviruses bearing the
      respective cDNAs. The biological activity of proCD was demonstrated by its pH
      dependent autoactivation to pseudocathepsin D and that of proSAP was demonstrated
      by feeding to saposin-deficient cultured cells that corrected the storage of
      radioactive glycolipids. In gel filtration, proSAP behaved as an oligomer and
      proCD as a monomer. ProSAP altered the elution of proCD such that the latter was
      shifted into proSAP-containing fractions. ProSAP did not change the elution of
      mature cathepsin D. Using surface plasmon resonance and an immobilized
      biotinylated proCD, binding of proSAP was demonstrated under neutral and weakly
      acidic conditions. At pH 6.8, specific binding appeared to involve more than one
      binding site on a proSAP oligomer. The dissociation of the first site was
      characterized by a K(D1) of 5.8+/-2.9x10(-8) M(-1) (calculated for the monomer).
      ProSAP stimulated the autoactivation of proCD and also the activity of
      pseudocathepsin D. Concomitant with the activation, proSAP behaved as a substrate
      yielding tri- and disaposins and smaller fragments. Our results demonstrate that
      proSAP forms oligomers that are capable of binding proCD spontaneously and
      independent of the mammalian type N-glycosylation but not capable of binding
      mature cathepsin D. In addition to binding proSAP, proCD behaves as an
      autoactivable and processing enzyme and its binding partner as an activator and
      substrate.

PMID- 15255781
TI  - 8-isoprostane increases scavenger receptor A and matrix metalloproteinase
      activity in THP-1 macrophages, resulting in long-lived foam cells.
AB  - BACKGROUND: Oxidative stress is a key factor in atherogenesis, in which it is
      closely associated with the inflammation and formation of bioactive lipids.
      Although 8-isoprostane is regarded as a reliable marker of oxidative stress in
      vivo, the pathogenic role of this F(2)-isoprostane in atherogenesis is far from
      clear. Based on the important role of foam cells in the initiation and
      progression of atherosclerosis we hereby examined the ability of 8-isoprostane to
      modulate oxidized (ox)LDL-induced foam cell formation and the function of these
      cells, particularly focusing on the effect on matrix degradation. METHODS AND
      RESULTS: 8-isoprostane (10 micro M) augmented the oxLDL-induced (20 micro g mL(
      1)) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and
      lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane
      induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and
      protein level], assessed by RT-PCR and Western blotting, respectively. Moreover,
      8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving
      both mitochondrial-protective and caspase-suppressive mechanisms. Along with
      these changes, 8-isoprostane increased the oxLDL-induced gene expression of
      matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue
      inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity.
      CONCLUSIONS: We show that 8-isoprostane increases foam cell formation at least
      partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells,
      inducing long-lived foam cells with enhanced matrix degrading capacity. Our
      findings further support a role for 8-isoprostane not only as a marker of
      oxidative stress in patients with atherosclerotic disorders, but also as a
      mediator in atherogenesis and plaque destabilization.

PMID- 15255782
TI  - Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during
      resuscitation: effects of oxygen and carbon dioxide.
AB  - BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction, and it is
      important to prevent further tissue injury during resuscitation. There is
      increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved
      in myocardial hypoxaemia-reoxygenation injury. OBJECTIVE: To assess MMPs and
      antioxidant capacity in newborn pigs after global ischaemia and subsequent
      resuscitation with ambient air or 100% O(2) at different PaCO(2)-levels. METHODS:
      Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with
      21% or 100% O(2) at different PaCO(2) levels after a hypoxic insult, and
      thereafter observed for 150 min. In myocardial tissue extracts, MMPs were
      analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP).
      Total endogenous antioxidant capacity in myocardial tissue extracts was measured
      by the oxygen radical absorbance capacity (ORAC) assay. RESULTS: Matrix
      metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was
      higher in piglets resuscitated with 100% O(2) than with ambient air (P = 0.012).
      The ORAC value was considerably decreased (P < 0.001). In piglets with elevated
      PaCO(2), total MMP-activity in the right ventricle was more increased than in the
      left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher
      in the piglets with low PaCO(2) than in the piglets with elevated PaCO(2) (P =
      0.013). CONCLUSION: In hypoxaemia-reoxygenation injury the MMP-2 level was highly
      increased and was most elevated in the piglets resuscitated with 100% O(2).
      Antioxidant capacity was considerably decreased. Assessed by total MMP-activity,
      elevated PaCO(2) during resuscitation might protect the left ventricle, and
      probably increase right ventricle injury of the myocardium.

PMID- 15255783
TI  - HDL metabolic activities in a boy with lipoprotein lipase deficiency and his
      family.
AB  - BACKGROUND: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessively
      inherited disease characterized by elevated triglyceride, low total cholesterol
      and quantitative and qualitative alterations of high-density lipoprotein (HDL).
      The aim of the present study was to explore HDL metabolic activities in a patient
      with LPL deficiency and in his family (n = 11). MATERIALS AND METHODS: Subjects
      were divided into four groups: proband (Ser447Stop/Arg170Leu carrier), Ser447Stop
      carriers, Arg170Leu carriers and silent mutation/wild-type carriers (controls).
      Cholesterol efflux from Fu5AH cells, lecithin:cholesterol acyltransferase (LCAT),
      cholesteryl ester transfer protein (CETP), paraoxonase 1 (PON1) and platelet
      activating factor acetylhydrolase (PAF-AH) activities were evaluated. RESULTS:
      Comparison between the proband and the control group revealed that the boy had
      significantly reduced cholesterol efflux (P < 0.001), conserved LCAT activity (P
      > 0.05) and increased CETP activity (P < 0.001). As regards antioxidant enzymes,
      while PON1 activity was higher in the proband than in the controls (P < 0.0001),
      PAF-AH activity was reduced (P < 0.05). The other groups did not show relevant
      differences in comparison with controls. CONCLUSIONS: The presence of one
      mutation was not enough to introduce important modifications in HDL functions.
      Markedly reduced HDL levels can keep certain normal enzymatic activities, which
      probably tend to counteract the deleterious effects of LPL deficiency.

PMID- 15255784
TI  - Selenium supplementation decreases nuclear factor-kappa B activity in peripheral
      blood mononuclear cells from type 2 diabetic patients.
AB  - OBJECTIVE: The role of selenium in preventing cardiovascular diseases has been
      largely described. Oxidative stress and the subsequent activation of nuclear
      factor-kappa B (NF-kappaB) have been linked to the development of vascular
      complications. We investigated the effects of selenium supplementation in type 2
      diabetic patients on several oxidative stress parameters and NF-kappaB activity.
      METHODS: We enrolled 56 type 2 diabetic patients with similar glycaemic control:
      21 were supplemented by selenium (960 micro g d(-1), 3 months) and 27 received a
      placebo, and 10 nondiabetic subjects formed the control group. To determine NF
      kappaB activation, we used an electrophoretic mobility shift assay followed by a
      semi-quantitative determination of NF-kappaB in peripheral blood mononuclear
      cells. RESULTS: Selenium treatment resulted in a significant increase in plasma
      selenium and red-cell Se GSH px activity. It had no effect on lipid peroxidation
      measured by malone-dialdehyde (MDA) or on red-cell Cu/Zn SOD. NF-kappaB activity
      was increased by 80% in diabetic patients. In patients receiving selenium
      supplementation, selenium NF-kappaB activity was significantly reduced, reaching
      the same level as the nondiabetic control group. CONCLUSION: In type 2 diabetic
      patients, activation of NF-kappaB measured in peripheral blood monocytes can be
      reduced by selenium supplementation, confirming its importance in the prevention
      of cardiovascular diseases.

PMID- 15255785
TI  - Impaired synthesis and action of antiaggregating cyclic nucleotides in platelets
      from obese subjects: possible role in platelet hyperactivation in obesity.
AB  - BACKGROUND: Subjects with central obesity exhibit platelet hyperactivity, which
      is involved in the atherosclerotic process and therefore can account for the
      increased risk of cardiovascular morbidity and mortality. The aim of the study
      was to evaluate whether alterations of platelet function in obesity involve
      synthesis and/or action of the two antiaggregating cyclic nucleotides adenosine
      3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate
      (cGMP). MATERIALS AND METHODS: In platelets from 16 obese and 15 control subjects
      we investigated the influence on platelet responses to the Adenosine-5
      diphosphate sodium salt (ADP) exerted by (i) prostacyclin analogue Iloprost (0.31
      5 nmol L(-1)) and the cAMP analogue 8-bromo-cAMP (10-500 micro mol L(-1)); and by
      (ii) nitric oxide (NO) donor sodium nitroprusside (SNP) (5-100 micro mol L(-1))
      and the cGMP analogue 8-bromo-cGMP (10-500 micro mol L(-1)). IC(50) (minimal
      concentration of each inhibitor necessary to reduce platelet response to ADP by
      half) was determined. Iloprost and SNP ability to increase cyclic nucleotides was
      also measured. RESULTS: Significantly greater IC(50) were observed in obese
      subjects than in healthy controls (1.59 +/- 0.16 vs. 0.80 +/- 0.08 nmol L(-1), P
      = 0.0001 for Iloprost, and 27.6 +/- 6.5 vs. 7.0 +/- 1.7 micro mol L(-1), P =
      0.006, for SNP); when data from control and obese subjects were pooled together,
      IC(50) of Iloprost and SNP correlated with the homeostasis model assessment (HOMA
      IR), which is a parameter used to measure the insulin resistance (r = 0.588, P =
      0.029 and r = 0.640, P = 0.006, respectively). Also the antiaggregating effect of
      8-Br-cAMP and 8-Br-cGMP was smaller in the obese subjects. Finally, the ability
      of Iloprost to increase platelet cAMP and the ability of SNP to increase both
      cGMP and cAMP were reduced in obese subjects. CONCLUSIONS: Platelet resistance to
      the antiaggregating effects of prostacyclin and NO in obesity is attributable to
      impairment of cyclic nucleotide synthesis and action. As cyclic nucleotides are
      the main effectors of platelet antiaggregation, the resistance to them can
      account for platelet hyperactivity in obesity.

PMID- 15255786
TI  - Restoration of early insulin secretion after a meal in type 2 diabetes: effects
      on lipid and glucose metabolism.
AB  - BACKGROUND: In type 2 diabetes (T2D) insulin secretion after a meal is delayed;
      this may have an impact on the development of hyperglycaemia and hyperlipidaemia.
      DESIGN: To investigate this, a meal was given to 15 T2D (age 52 +/- 2 years, BMI
      25 +/- 0.8 kg m(-2)) on three different occasions: (1) without treatment, (2)
      after 120 mg of nateglinide before the meal (acute treatment), and (3) after 3
      months of nateglinide (120 mg t.i.d., chronic treatment). Fifteen healthy
      subjects (CON, age 48 +/- 2 years, BMI 24 +/- 0.5 kg m(-2)) were also studied.
      Blood was withdrawn for 360 min from veins draining the anterior abdominal
      subcutaneous adipose tissue (AD) and from an arterialized hand vein. Blood flow
      (BF) in AD was measured with (133)Xe. Lipoprotein lipase activity (LPL) was
      calculated as the triacylglycerol (TAG) flux across AD, and hormone-sensitive
      lipase (HSL) as the glycerol flux minus LPL. RESULTS: (1) In T2D the increase in
      prandial insulin secretion was delayed; postprandial nonesterified fatty acid
      (NEFA) and TAG levels in blood were increased, while BF, LPL and TAG clearance
      were blunted vs. CON. (2) Acute or chronic nateglinide treatment induced a prompt
      increase in prandial insulin secretion, resulting in a decrease in blood glucose
      and NEFA levels owing to suppression of HSL, while BF, LPL and TAG clearance
      remained suppressed. CONCLUSIONS: In T2D, restoration of early phase insulin
      secretion improved postprandial hyperglycaemia and suppressed endogenous
      lipolysis, resulting in suppression of NEFA levels. These results suggest that in
      nonobese T2D, metabolic defects may result, to a large extent, from the delay in
      prandial insulin secretion.

PMID- 15255787
TI  - Cholecystokinin-1 receptor protein up-regulation during pancreatic regeneration
      after acute haemorrhagic pancreatitis in rats.
AB  - BACKGROUND: Cholecystokinin (CCK) plays an important role in regeneration after
      acute pancreatitis in rats. The present study was aimed to elucidate the role of
      CCK-1 receptor (CCK-1R) in acute pancreatitis. We investigated the serial changes
      in CCK-1R mRNA and protein levels and their immunolocalization after acute
      haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal
      infusion of 4% sodium taurocholate (100 micro L 100 g(-1) body weight). METHODS:
      Histological changes were evaluated by haematoxylin and eosin staining.
      Pancreatic CCK-1R mRNA was determined by Northern blot analysis. Pancreatic CCK
      1R protein was evaluated by immunoblot analysis and immunohistochemistry with a
      polyclonal antibody against rat CCK-1R protein. RESULTS: Histological findings
      revealed that newly formed acinar cells were detected at the periphery of tubular
      complexes on day 14, and normal architecture of lobules was observed focally on
      day 21. Pancreatic CCK-1R mRNA peaked on day 3 and thereafter gradually
      decreased. Cholecystokinin-1R protein rapidly increased after induction of
      pancreatitits, reaching a maximal level on day 3. On day 3, intense
      immunoreactivity for CCK-1R protein was observed in both the cytoplasm of
      vacuolized acinar cells and the tubular complexes. In the regenerative process
      after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK
      1R mRNA and protein increased, and intense immunoreactivity for CCK-1R protein
      was observed in tubular complexes in the cytoplasm of regenerated acinar cells.
      CONCLUSION: These results suggest that CCK-1R contributes to pancreatic
      regeneration after acute haemorrhagic pancreatitis and that tubular complexes are
      involved in the process of acinar cell regeneration following pancreatic injury.

PMID- 15255788
TI  - Effects of low-dose dopamine on ventilation in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Dopamine plays an important role in the regulation of respiration and
      low-dose dopamine infusion is associated with a decreased respiratory drive
      response to hypoxia in animals and humans. The effects of dopamine on ventilation
      in patients with chronic obstructive pulmonary disease (COPD) is unknown. We
      tested the hypothesis that dopamine inhibits ventilation in patients with COPD.
      MATERIALS AND METHODS: In a double-blinded, cross-over, placebo-controlled,
      randomized study we studied nine patients with decompensated COPD, ventilated in
      the pressure support mode in the intensive care unit (ICU) and five ambulatory
      patients with stable COPD. All patients received 5 micro g kg(-1) min(-1) of
      dopamine or an equivalent volume of 5% glucose solution. RESULTS: In the
      mechanically ventilated COPD patients, there was no difference in the effects of
      dopamine compared with placebo on blood pressure, heart rate, minute ventilation
      (-0.5 +/- 1.1 vs. -0.2 +/- 0.9 L min(-1), P = 0.46, respectively), respiratory
      rate (-0.4 +/- 2.7 vs. -0.3 +/- 2.1 min(-1), P = 0.96), PaO(2) (-5 +/- 4 vs. -5
      +/- 10 mmHg, P = 0.90, respectively), or PaCO(2) (-0.7 +/- 1.4 vs. -1.0 +/- 3.4
      mmHg, P = 0.83, respectively). In spontaneously breathing stable patients,
      dopamine increased systolic blood pressure (P = 0.02) but did not influence other
      haemodynamic and respiratory variables. CONCLUSION: Although low-dose dopamine
      has been shown to depress ventilation in a variety of conditions, it does not
      compromise ventilation in COPD patients either breathing spontaneously or when
      weaned using pressure support ventilation.

PMID- 15255789
TI  - Gradient of proteolytic enzymes, their inhibitors and matrix proteins expression
      in a ruptured abdominal aortic aneurysm.

PMID- 15255790
TI  - Fabry outcome survey: need for documentation of dermatological, ophthalmological
      and psychiatric affections.

PMID- 15255795
TI  - A comparison of lung function methods for assessing dose-response effects of
      salbutamol.
AB  - Pulmonary function methods which are able to detect small pharmacological effects
      may be useful for assessing the full dose-response curve of bronchodilatators. We
      compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography
      (sGaw) and spirometry [forced expiratory volume in 1 s (FEV(1)), maximal mid
      expiratory flow rate (MMEF)] to measure the dose-response effects of salbutamol
      in 12 healthy subjects, 12 mild asthmatics (mean FEV(1) 96% predicted) and 12
      moderate asthmatics (mean FEV(1) 63% predicted). The techniques were performed
      twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 microg was
      administered. The sensitivity of the methods were compared by determining the
      lowest dose that caused changes greater than variability. In healthy subjects
      significant changes (p < or = 0.05) were observed only in FEV(1) (4.1%) and MMEF
      (14.6%) at 100 microg and sGaw (25.6%) and R20 (8.3%) at 200 microg. In mild
      asthmatics significant changes were observed in sGaw (15.9%) at 10 microg, X5
      (23%), RF (20.3%) and MMEF (15.7%) at 20 microg, R5 (13.9%) and R20 (9.4%) at 100
      microg and FEV(1) (7.1%) at 200 microg. All measurements except R20 demonstrated
      significant changes at 10 micro g in moderate asthmatics. The most sensitive test
      for assessing bronchodilatation is different in healthy subjects and asthmatics,
      and varies with severity of airflow obstruction.

PMID- 15255794
TI  - What is the best size descriptor to use for pharmacokinetic studies in the obese?
AB  - The prevalence of obesity in the western world is dramatically rising, with many
      of these individuals requiring therapeutic intervention for a variety of disease
      states. Despite the growing prevalence of obesity there is a paucity of
      information describing how doses should be adjusted, or indeed whether they need
      to be adjusted, in the clinical setting. This review is aimed at identifying
      which descriptors of body size provide the most information about the
      relationship between dose and concentration in the obese. The size descriptors,
      weight, lean body weight, ideal body weight, body surface area, body mass index,
      fat-free mass, percent ideal body weight, adjusted body weight and predicted
      normal body weight were considered as potential size descriptors. We conducted an
      extensive review of the literature to identify studies that have assessed the
      quantitative relationship between the parameters clearance (CL) and volume of
      distribution (V) and these descriptors of body size. Surprisingly few studies
      have addressed the relationship between obesity and CL or V in a quantitative
      manner. Despite the lack of studies there were consistent findings: (i) most
      studies found total body weight to be the best descriptor of V. A further
      analysis of the studies that have addressed V found that total body weight or
      another descriptor that incorporated fat mass was the preferred descriptor for
      drugs that have high lipophilicity; (ii) in contrast, CL was best described by
      lean body mass and no apparent relationship between lipophilicity or clearance
      mechanism and preference for body size descriptor was found. In conclusion, no
      single descriptor described the influence of body size on both CL and V equally
      well. For drugs that are dosed chronically, and therefore CL is of primary
      concern, dosing for obese patients should not be based on their total weight. If
      a weight-based dose individualization is required then we would suggest that
      chronic drug dosing in the obese subject should be based on lean body weight, at
      least until a more robust size descriptor becomes available.

PMID- 15255796
TI  - Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and
      healthy males.
AB  - AIMS: 1) To characterize the population pharmacokinetics of apomine in healthy
      males and in male and female patients with solid tumours and 2) to understand
      more fully the influence of induction and between- and within-subject variability
      on exposure to drug using Monte Carlo simulation. METHODS: Apomine was
      administered once- or twice-daily with or without food in single and multiple
      oral doses of 30-2100 mg to healthy males (n = 19) and patients with solid
      tumours (n = 19). The data were divided into model development and validation
      sets. Models were developed using standard population methods. These were the
      identification of an appropriate base model, calculation of the empirical Bayes
      estimates of the primary pharmacokinetic parameters, covariate screening, forward
      stepwise addition of covariates using the likelihood ratio test as a model
      selection criteria, and backwards elimination to obtain the final model. To study
      the influence of data from individual subjects, the model development dataset was
      subjected to the delete-1 jack-knife and the final model was fitted to each jack
      knifed dataset. Principal components analysis of the jack-knifed matrix of model
      parameters identified two influential subjects who were removed from the dataset,
      and the final model contained data from the remaining subjects. Model validation
      was examined using goodness of fit statistics and relative error measures using
      independent datasets from cancer patients. The model provided a reasonable
      approximation to the pharmacokinetic measurements in the validation datasets.
      Computer simulations were undertaken to understand further the pharmacokinetics
      of apomine in otherwise healthy females, a population not yet studied. RESULTS:
      Apomine pharmacokinetics were complex and consistent with a two-compartment model
      with a lag-time. Apparent oral clearance at baseline and apparent volume of
      distribution at steady-state were larger in healthy males than in cancer patients
      (41 ml h(-1) and 14.1 l vs 10 ml h(-1) and 8.9 l, respectively, for a 75 kg
      person). Clearance was time-variant showing a maximal increase with full
      induction of 320 ml h(-1), independent of patient type. The time to reach 50%
      maximal induction was about 2 days. The fraction of drug absorbed was relatively
      constant at doses less than 100-200 mg once daily but decreased at higher doses.
      Food also decreased relative bioavailability by 36%. Patient characteristics had
      no effect on apomine pharmacokinetics except for weight, which was proportional
      to the volume of the central compartment. Between-subject variability (68% for
      clearance, 30% for central volume, and 141% for peripheral volume) was moderate
      to large and independent of patient type. Inter-occasion variability was small
      (18% for both clearance and central volume). Residual variability was modelled
      with an additive and proportional error model. Cancer patients had slightly
      higher plasma concentrations than healthy males but this difference was probably
      not clinically significant. Steady-state was reached in about 3-4 days after once
      daily drug administration. The half-life of apomine after three weeks of once
      daily dosing was 41 h in cancer patients and 32 h in healthy males. CONCLUSIONS:
      A population model for apomine has been developed has been developed that
      characterizes its pharmacokinetics in cancer patients and healthy subjects under
      a variety of conditions.

PMID- 15255797
TI  - Bioavailabilities of rectal and oral methadone in healthy subjects.
AB  - AIMS: Rectal administration of methadone may be an alternative to intravenous and
      oral dosing in cancer pain, but the bioavailability of the rectal route is not
      known. The aim of this study was to compare the absolute rectal bioavailability
      of methadone with its oral bioavailability in healthy humans. METHODS: Seven
      healthy subjects (six males, one female, aged 20-39 years) received 10 mg d(5)
      methadone-HCl rectally (5 ml in 20% glycofurol) together with either d(0)
      methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood
      samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn
      for up to 96 h. Noninvasive infrared pupillometry was performed at the same time
      as blood sampling. RESULTS: The mean absolute rectal bioavailability of methadone
      was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean
      (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing
      with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation
      of the metabolite EDDP did not differ between routes of administration. Single
      doses of methadone had a duration of action of at least 10 h and were well
      tolerated. CONCLUSIONS: Rectal administration of methadone results in rapid
      absorption, a high bioavailability and long duration of action. No evidence of
      presystemic elimination was seen. Rectal methadone has characteristics that make
      it a potential alternative to intravenous and oral administration, particularly
      in cancer pain and palliative care.

PMID- 15255798
TI  - Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy
      Chinese children: a comparison of Han and Yao ethnic groups.
AB  - AIMS: Ethnicity is an important variable influencing drug response. Thiopurine S
      methyltransferase (TPMT) plays an important role in the metabolism of thiopurine
      drugs. Previous population studies have identified ethnic variations in both
      phenotype and genotype of TPMT, but limited information is available within
      Chinese population that comprises at least 56 ethnic groups. The current study
      was conducted to compare both phenotype and genotype of TPMT in healthy Han and
      Yao Chinese children. METHODS: TPMT activity was measured in healthy Chinese
      children by a HPLC assay (n = 213, 87 Han Chinese and 126 Yao Chinese). Allele
      specific polymerase chain reaction (PCR) and PCR-restriction fragment length
      polymorphism (RFLP) were used to determine the frequency of TPMT mutant alleles
      (TPMT*2, TPMT*3 A, TPMT*3B and TPMT*3C) in these children. RESULTS: There was no
      significant difference in the mean TPMT activity between Han and Yao Chinese
      children. A unimodal distribution of TPMT activity in Chinese children was found
      and the mean TPMT activity was 13.32 +/- 3.49 U ml(-1) RBC. TPMT activity was not
      found to differ with gender, but tended to increase with age in Yao Chinese
      children. TPMT*2, TPMT*3B and TPMT*3A were not detected, and only one TPMT*3C
      heterozygote (Han child) was identified in 213 Chinese children. Erythrocyte TPMT
      activity of this TPMT*3C heterozygote was 12.36 U ml(-1) RBC. The frequency of
      the known mutant TPMT alleles was 0.2%[1/426] in Chinese children. CONCLUSION:
      The frequency distribution of RBC TPMT activity was unimodal. The frequency of
      the known mutant TPMT alleles in Chinese Children is low and TPMT*3C appears to
      be the most prevalent among the tested mutant TPMT alleles in this population.

PMID- 15255799
TI  - Endothelial venodilator response in carriers of genetic polymorphisms involved in
      NO synthesis and degradation.
AB  - AIMS: Polymorphisms of the NOSIII gene and of the CYBA gene have been associated
      with a number of pathological conditions such as arterial hypertension, coronary
      artery disease, and myocardial infarction. Because endothelium-dependent
      vasodilation is impaired in these disorders, we hypothesized that polymorphisms
      of NOSIII or CYBA might modulate endothelial function of venous capacitance
      vessels already before cardiovascular disease becomes overt. METHODS: Endothelium
      dependent and -independent venodilation was assessed by measuring local vascular
      responses to bradykinin and sodium nitroprusside in the dorsal hand vein after
      preconstriction with phenylephrine in 72 healthy male Caucasians after careful
      exclusion of cardiovascular risk factors. Genotyping was performed for
      polymorphisms of the NOSIII gene (T-786C, G894T, (CA)(n)) and the CYBA gene
      (C242T). RESULTS: Genotype distribution for each polymorphism followed the Hardy
      Weinberg equilibrium. In all studied single nucleotide polymorphisms no
      significant difference between the respective genotypes and the venodilator
      response to either sodium nitroprusside or bradykinin was observed, and the
      number of CA repeat copies was not related to the venodilator response to
      bradykinin. Mean venodilation induced by bradykinin 50 ng min(-1) (+/-SEM) for
      homozygote carriers of the single nucleotide polymorphisms was 48.9 +/- 8.5%
      venodilation (G894T; wild type: 49.8 +/- 6.9), 50.3 +/- 11.0% venodilation (T
      786C; wild type: 42.6 +/- 5.2), and 30.4 +/- 9.1% venodilation (C242T; wild type:
      49.2 +/- 6.0), respectively. CONCLUSIONS: This study suggests that the studied
      polymorphisms of NOSIII and CYBA do not significantly modulate endothelium
      dependent venodilation in individuals without vascular risk factors.

PMID- 15255800
TI  - Antipsychotic polypharmacy in patients with schizophrenia: a multicentre
      comparative study in East Asia.
AB  - AIMS: Previous studies of the prescription patterns of psychotropic medications
      in patients with schizophrenia have highlighted a high rate of antipsychotic
      polypharmacy, but data in Asia are sparse. This study seeks to examine the
      prevalence of antipsychotic polypharmacy in patients with schizophrenia and
      compare the differences between patients receiving one vs. those receiving more
      than one antipsychotic. METHODS: Antipsychotic prescription for a sample of 2399
      patients with schizophrenia from six countries and territories was evaluated.
      Daily doses of antipsychotic medications were converted to standard
      chlorpromazine equivalents (CPZ). RESULTS: Antipsychotic polypharmacy was found
      in 45.7% (n = 1097) of the patients with wide intercountry variations.
      Polypharmacy was associated with male gender [odds ratio (OR) 1.24, 95%
      confidence interval (CI) 1.06, 1.46, P < 0.01], advanced age (t = -7.81, d.f. =
      2396, P < 0.001), psychiatric hospital setting (OR 1.34, 95% CI 1.11, 1.62) as
      well as higher daily CPZeq doses (411.47 vs. 983.10 CPZeq day(-1), z = -25.94, P
      < 0.001), anticholinergic use (OR 3.17, 95% CI 2.65, 3.79, P < 0.001) and less
      use of an atypical antipsychotic drug (OR 0.83, 95% CI 0.71, 0.98, P < 0.05). On
      multivariate analysis, country, age and duration of illness were significantly
      associated with antipsychotic polypharmacy. CONCLUSION: This study highlighted
      the wide intercountry variations of antipsychotic polypharmacy which are likely
      to be influenced by a complex combination of clinical, setting, cultural and
      personal practice factors, requiring more research.

PMID- 15255801
TI  - Increased treatment failure after 3-days' courses of nitrofurantoin and
      trimethoprim for urinary tract infections in women: a population-based
      retrospective cohort study using the PHARMO database.
AB  - AIM: To assess determinants of treatment failure after antimicrobial therapy of
      urinary tract infections in women. METHODS: In primary care 16 703 Dutch women
      who received a first course (3, 5 or 7 days) of trimethoprim, nitrofurantoin or
      norfloxacin between 1 January 1992 through 31 December 1997 and who were between
      15 and 65 years old at the day of first use were selected. Failure of the initial
      treatment was defined as a further prescription for one of these three
      antibiotics or for cotrimoxazole, amoxicillin, ciprofloxacin or ofloxacin, within
      31 days after the end of the initial therapy. RESULTS: Treatment failure rate was
      14.4% in patients treated with trimethoprim and nitrofurantoin and 9.6% in
      patients treated with norfloxacin. A multivariate analysis showed that 5
      days'[RR(NIT) 0.67, 95% confidence interval (CI) 0.57, 0.82, RR(TRI) 0.82, 95% CI
      0.73, 0.91] and 7 days' (RR(NIT) 0.64, 95% CI 0.53, 0.77, RR(TRI) 0.85, 95% CI
      0.71, 1.02) trimethoprim and nitrofurantoin treatment appeared to be more
      effective than a 3-day treatment (reference category). Other factors increasing
      treatment failure rates were the age of the patient, the year of therapy and
      previous hospitalization. CONCLUSIONS: It may be concluded that 3-day courses of
      nitrofurantoin and trimethoprim are less effective than 5- and 7-day courses in
      the treatment of uncomplicated urinary tract infections in women.

PMID- 15255802
TI  - Robustness of chlorzoxazone as an in vivo measure of cytochrome P450 2E1
      activity.
AB  - AIMS: Chlorzoxazone is metabolized by cytochrome P450 2E1 (CYP2E1) to a single
      oxidized metabolite, 6-hydroxychlorzoxazone. The aim of the study was to test the
      robustness of chlorzoxazone as an in vivo probe of CYP2E1 activity in humans,
      with emphasis on investigating short-term and long-term intra-individual
      variabilities and effects of different doses of the drug. In addition, the
      influences of body build, drug metabolizing enzyme genotype, blood sampling time,
      and moderate recent ethanol intake were investigated. METHODS: The 6
      hydroxychlorzoxazone:chlorzoxazone (metabolic) ratio in plasma was measured at 2
      h in 28 male and nine female volunteers following a single oral dose of 500 mg
      chlorzoxazone. Similarly, the metabolic ratios at 4 h and 6 h were measured in 20
      of the males. The metabolic ratio at 2 h was also determined 1.5 and 2.5 years
      later in 13 and seven males, respectively, and weekly for 3 weeks in seven males,
      after a dose of 500 mg, once at higher (750 mg) and lower (250 mg) doses, and
      once (500 mg) following moderate ethanol intake (0.5 g kg(-1) body weight) the
      preceding evening. Genotypes were determined for CYP2E1 as well as for N
      acetyltransferase 2 and glutathione transferase M1. RESULTS: Excluding an outlier
      (ratio = 1.6) the metabolic ratio at 2 h ranged from 0.12 to 0.61 (n = 36). A
      positive correlation with body weight (r = 0.61, P < 0.001) suggested dose
      dependent metabolism of chlorzoxazone. The metabolic ratio decreased with
      increasing chlorzoxazone dose (P = 0.01), again suggesting dose-dependent
      metabolism. Long-term (yearly intervals) and short-term (weekly intervals) intra-
      and interindividual variabilities in metabolic ratio were similar (30% and 63%vs
      28% and 54%, respectively). Both inter- and intra-individual variabilities tended
      to decrease with increasing dose of chlorzoxazone. There was no significant
      influence of moderate ethanol intake the preceding evening, or of CYP2E1 genotype
      on the metabolic ratio. CONCLUSIONS: The relatively low intra-individual
      variability in the metabolism of chlorzoxazone suggests that a single-sample
      procedure may suffice to assess CYP2E1 activity in vivo. However, chlorzoxazone
      metabolism is dose-dependent at commonly used doses and it is therefore advisable
      to adjust the dose for body weight. Moderate intake of ethanol the preceding
      evening did not significantly affect the chlorzoxazone metabolic ratio.

PMID- 15255803
TI  - Leflunomide in active rheumatoid arthritis: a prospective study in daily
      practice.
AB  - AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions
      and withdrawal from leflunomide in an outpatient population with rheumatoid
      arthritis in a setting of care-as-usual. METHODS: In this prospective case series
      study, a standard dataset was collected from outpatient medical records,
      including patient and disease characteristics, data on leflunomide use and
      adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis
      patients started leflunomide. Median (range) follow-up duration was 317 (11-911)
      days. Sixty-five percent of patients experienced at least one adverse drug
      reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from
      leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of
      efficacy (13%). The overall incidence density for withdrawal from leflunomide was
      56.2 per 100 patient years. Complete data for calculating efficacy using a
      validated disease activity score on 28 joints (DAS(28)) was available for 48, 36,
      and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12
      month period after start of leflunomide treatment 76% of the evaluable patients
      were classified as moderate or good responders according to the DAS(28) response
      criteria. CONCLUSIONS: In the setting of care-as-usual rheumatoid arthritis
      patients starting leflunomide frequently experienced adverse drug reactions. More
      than half of the patients withdrew from leflunomide treatment within 1 year of
      starting leflunomide treatment, mainly because of adverse drug reactions.

PMID- 15255804
TI  - In vitro fertilization and childhood retinoblastoma.
AB  - AIMS: To estimate the frequency of childhood retinoblastoma among children
      conceived by in vitro fertilization (IVF). METHODS: Using the United Kingdom
      based General Practice Research Database (GPRD), we identified all live births,
      cases of retinoblastoma and IVF procedures occurring between January 1989 and
      December 2001. RESULTS: We identified 0 cases of retinoblastoma among 176
      children conceived by IVF (Risk = 0/176, one-sided 97.5% CI 0, 0.02) and 24 cases
      of retinoblastoma diagnosed before age 5 years among 358,094 children not
      conceived by IVF (6.7 cases per 100,000 births [95% CI 4.5, 10]). CONCLUSIONS:
      These data provide some reassurance that children born as a result of IVF are not
      at markedly increased risk of retinoblastoma.

PMID- 15255805
TI  - In vitro blood distribution and plasma protein binding of the tyrosine kinase
      inhibitor imatinib and its active metabolite, CGP74588, in rat, mouse, dog,
      monkey, healthy humans and patients with acute lymphatic leukaemia.
AB  - AIMS: To determine blood binding parameters of imatinib and its metabolite
      CGP74588 in humans and non-human species. METHODS: The blood distribution and
      protein binding of imatinib and CGP74588 were determined in vitro using (14)C
      labelled compounds. RESULTS: The mean fraction of imatinib in plasma (f(p)) was
      45% in dog, 50% in mouse, 65% in rat, 70% in healthy humans and up to 92% in
      acute lymphatic leukaemia (AML) patients. Similarly, f(p) for CGP74588 was low in
      dog and monkey (30%), higher in rat, mouse and humans (70%) and highest in some
      AML patients (90%). The unbound fraction of imatinib and CGP74588 in plasma was
      lower in rat, mouse, healthy humans and AML patients (2.3-6.5% at concentrations
      < or = 5000 ng ml(-1)) compared to monkey and dog (7.6-19%). Both compounds
      displayed high binding to human alpha(1)-acid glycoprotein. AML patients had a
      reduced haematocrit and showed greatest variability in their blood binding
      parameters. CONCLUSION: Imatinib and CGP74588 displayed very similar blood
      binding parameters within all species/groups investigated. The five species
      clustered into two distinct groups with rat, mouse and humans being clearly
      different from dog and monkey. For both compounds, higher protein binding was
      associated with a decreased partitioning into blood cells.

PMID- 15255806
TI  - Training in paediatric clinical pharmacology in the UK.
AB  - AIMS: To produce a training programme in paediatric clinical pharmacology.
      METHODS: A working group, consisting of clinical pharmacologists (paediatric and
      adult), general paediatricians and the pharmaceutical industry was established to
      produce the training programme. RESULTS: Following a two year training programme
      in general paediatrics, a three year training programme in clinical pharmacology
      has been established. This includes one year of research in clinical pharmacology
      (paediatric or adult). The other two years involve training in different aspects
      of paediatric clinical pharmacology and general paediatrics. CONCLUSION: The
      existence of a formal training programme should result in a significant increase
      in the number of paediatric clinical pharmacologists.

PMID- 15255807
TI  - Plasma concentrations during naltrexone implant treatment of opiate-dependent
      patients.
AB  - AIMS: To evaluate individual variations in plasma concentrations over time in
      patients with naltrexone implants. METHODS: Ten opioid-dependent patients
      received up to four implants. Plasma samples were collected regularly for the
      analyses of naltrexone and the metabolite beta-naltrexol. RESULTS: The median
      naltrexone C(max) was 12.3 (range 5.8-22.1) ng ml(-1), the median T(max) was 1
      day (range 3 h to 35 days), and the median length of time that plasma
      concentrations were above 1 ng ml(-1) was 55 (range 30-80) days. Two patients
      reported heroin use without experiencing any effect. Tissue reactions were
      recorded in two patients after repeated implantation. CONCLUSION: Marked
      individual and intraindividual variations in naltrexone concentrations were
      observed. Further studies should be performed to evaluate the need for
      therapeutic drug monitoring during naltrexone implant treatment.

PMID- 15255808
TI  - Acute hypotensive effects of oral cisapride and erythromycin in healthy subjects.

PMID- 15255809
TI  - The use of urine to clarify the genotype of a patient with toxic phenytoin
      concentrations who had undergone peripheral blood stem cell transplantation.

PMID- 15255812
TI  - Semicarbazide-sensitive amine oxidase: role in the vasculature and vasodilation
      after in situ inhibition.
AB  - 1. The characteristics of semicarbazide-sensitive amine oxidase (SSAO) are
      reviewed and the unknown physiological or pathological role of this enzyme
      emphasized. 2. The various mechanisms of action proposed for the vasodilator drug
      hydralazine are considered. In particular, the inhibitory action on various
      enzymes, related or not to cardiovascular function, are discussed. 3. Studies
      linking inhibition of SSAO to hydralazine hypotension are reviewed and a general
      hypothesis relating both actions is presented. The hypothesis postulates that
      (a). vascular SSAO is involved in the regulation of vascular tone, and (b).
      hydralazine vasodilation is the consequence of vascular SSAO inhibition. 4.
      Evidence supporting these postulates is presented and vascular SSAO inhibition is
      proposed as a novel mechanism of vasodilation.

PMID- 15255813
TI  - AT(1)-receptor blockade and sympathetic neurotransmission in cardiovascular
      disease.
AB  - 1. The present survey is dealing with the interactions between the renin
      angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) in
      various organs and tissues, with an emphasis on the angiotensin AT-receptors
      located at the sympathetic nerve endings. 2. Angiotensin II, the main effector of
      the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in
      numerous organs and tissues, such as the central nervous system, the adrenal
      medulla, the sympathetic ganglia and the sympathetic nerve endings. These
      stimulatory effects are mediated by AT(1)-receptors and counteracted by AT(1)
      receptor antagonists. 3. Sympatho-inhibition at the level of the sympathetic
      nerve ending appears to be a class effect of the AT(1)-receptor blockers,
      mediated by presynaptic AT(1)-receptors. With respect to the ratio pre
      /postsynaptic AT(1)-receptor antagonism important quantitative differences
      between the various compounds were found. 4. Both the pre- and postjunctional
      receptors at the sympathetic nerve endings belong to the AT(1)-receptor
      population. However, the presynaptic receptors belong to the AT(1B)-subtype,
      whereas the postjunctional receptors probably belong to a different AT(1)
      receptor subpopulation. 5. Sympatho-inhibition is a class effect of the AT(1)
      receptor antagonists. In conditions in which the SNS plays a pathophysiological
      role, such as hypertension and congestive heart failure, this property may well
      be of therapeutic relevance.

PMID- 15255814
TI  - Prejunctional AT(1) receptor subtype-dependent modification of neurotransmitter
      releases in canine isolated splenic arteries.
AB  - 1. The regulation by angiotensin II (Ang II) formed locally on nerve-stimulated
      purinergic and adrenergic components of double-peaked vasoconstrictions in the
      canine splenic artery and Ang II receptor subtypes involved were investigated. 2.
      The perfusion of the precursor angiotensin I (Ang I, 0.1-1 nm) did not affect the
      vasoconstrictor responses to noradrenaline (NA, 0.03-1 nmol) and adenosine 5'
      triphosphate (ATP, 0.03-1 micromol). The second component vasoconstrictor
      response to nerve stimulation was dose dependently potentiated by Ang I (0.1-1
      nm). The first peaked constriction was slightly, but insignificantly increased.
      The potentiating effects of Ang I were abolished by KRH-594 (10 nm), a selective
      AT(1) receptor antagonist, but not by PD 123319 (1-10 nm), an AT(2) receptor
      antagonist. KRH-594 (10 nm) or PD 123319 (10 nm) never affected the
      vasoconstrictions to either NA or ATP. 3. The treatment with KRH-594 (1-10 nm)
      produced a greater inhibition on the second peaked response than the first one,
      although both of them were dose dependently inhibited. PD 123319 (1-10 nm) did
      not affect the vasoconstrictor responses induced by nerve stimulation. 4.
      Inhibition of angiotensin-converting enzyme with 10 nm enalaprilat reduced the
      second peaked response, having no significant inhibition on the first peaked
      response. A higher dose of enalaprilat (100 nm) produced a greater inhibition of
      the second peak than the first one. It reduced the second peak by approximately
      65%, while the first peak was decreased approximately 35%. After treatment with
      enalaprilat, Ang I (1 nm) failed to enhance the neuronal vascular response.
      Enalaprilat at doses used did not affect the vasoconstrictions to either NA or
      ATP. 5. The present results indicate that endogenously generated Ang II may
      produce a more marked potentiation of adrenergic transmission than purinergic
      transmission via activation of prejunctional AT(1) receptors.

PMID- 15255815
TI  - Differential regulation by Ca(2+) of calmodulin- and PKC-dependent contractile
      pathways in cat lower oesophageal sphincter.
AB  - 1. In the present investigation we examined the regulation of calmodulin (CaM)-
      and protein kinase C (PKC)-dependent pathways by cytosolic Ca(2+) in the
      contraction of cat lower oesophageal sphincter (LES). 2. Force developed in
      response to increasing doses of acetylcholine (ACh) was directly related to the
      increase of the [Ca(2+)](i) measured by fura-2. Thapsigargin, which depletes
      Ca(2+) stores, reduced the contraction and the [Ca(2+)](i). In addition,
      contraction in response to maximal ACh was reduced by the CaM inhibitor CGS9343B
      but not by the PKC inhibitor chelerythrine. The contraction in response to
      submaximal ACh was reduced by chelerythrine but not by CGS9343B. 3. In
      permeabilized cells, the contraction in response to low Ca(2+) (0.54 microm) was
      also reduced by CGS9343B. 4. The response to high Ca(2+) (1.0 microm) was reduced
      by CGS9343B. ACh also inhibited PKC activation induced by diacylglycerol, which
      activation is inhibited by the N-myristoylated peptide inhibitor derived from
      pseudosubstrate sequences of PKCalphabetagamma (myr-PKC-alphabetagamma), but not
      of myr-PKC-alpha. 5. These data are consistent with the view that activated CaM
      dependent pathways inhibit PKC-dependent pathways, this switch mechanism might be
      regulated by Ca(2+) in the LES.

PMID- 15255816
TI  - Coronary and aortic vasoconstriction by cathinone, the active constituent of
      khat.
AB  - 1. The psychostimulant constituent of khat leaves, S-(-)-cathinone, was examined
      for vascular activity on the coronary vasculature of guinea-pig-isolated perfused
      hearts and aortic ring preparations. 2. Cathinone caused coronary
      vasoconstriction, negative inotropy and negative chronotropy in isolated hearts.
      The major metabolite of cathinone after its ingestion, 1R.2S-(-)-norephedrine
      (norephedrine), also caused coronary vasoconstriction comparable with that by
      cathinone. Norephedrine, however, had no effect on force or rate of cardiac
      contractions. 3. Cocaine (10 microm) potentiated the coronary vasoconstriction
      and positive inotropy by noradrenaline indicating inhibition of neuronal uptake.
      The vasoconstriction and negative inotropy by cathinone, however, were not
      affected, indicating that its action was not via release of noradrenaline from
      sympathetic neurones. 4. The alpha(1)-adrenoceptor antagonist, prazosin, blocked
      the vasoconstriction by noradrenaline, but not that produced by cathinone in the
      presence of cocaine. This indicates that the coronary vasoconstriction by
      cathinone was not due to an action on alpha(1)-adrenoceptors either directly or
      indirectly through noradrenaline release. 5. Three repeated doses of cathinone
      displayed the same coronary vasoconstrictor responses, indicating a lack of
      tachyphylaxis and therefore confirming that the response was unlikely to be due
      to indirect sympathomimetic activity through release of noradrenaline. 6. In
      guinea-pig aortic rings, the order of vasoconstrictor activity was: noradrenaline
      > norephedrine > cathinone, with each causing approximately equivalent maximum
      responses. The time to reach plateau contractions was shortest for noradrenaline
      (5.1 +/- 0.5 min), then norephedrine (9.3 +/- 1.5 min) and cathinone the longest
      (25.4 +/- 3.2 min, 335 microm dose). 7 These results indicate that cathinone has
      vasoconstrictor activity which is not due to indirect or direct sympathomimetic
      activity. The precise mechanism for this vasoconstriction remains to be
      determined. The coronary vasoconstriction may explain the increased incidence of
      myocardial infarction in khat chewers, which may arise from coronary vasospasm.

PMID- 15255817
TI  - Co-localization of histamine and dopamine-beta-hydroxylase in sympathetic
      ganglion and release of histamine from cardiac sympathetic terminals of guinea
      pig.
AB  - 1. The aim of this study was to investigate the co-localization of histamine and
      dopamine-beta-hydroxylase in the superior cervical ganglion of guinea-pig and
      release of histamine from cardiac sympathetic terminals in guinea-pig isolated
      atrium. 2. Histidine decarboxylase (a histamine-synthesizing enzyme) mRNA signals
      were detected in the neurones of superior cervical ganglion of guinea-pig by in
      situ hybridization. The results of double-labelled immunofluorescence further
      confirmed the co-localization of histamine and dopamine-beta-hydroxylase in the
      large principle neurons and small intensely fluorescent cells in the superior
      cervical ganglion. The immunoreactivities of both histamine and dopamine-beta
      hydroxylase were significantly attenuated after 6-hydroxydopamine-induced lesion
      of sympathetic nerves. 3. The refractory electrical field stimulation caused the
      release of histamine from cardiac sympathetic terminals of guinea-pig isolated
      atria (112.14 +/- 40.34 ng x ml(-1)), which was significantly attenuated to 35 +/
      15.57 ng x ml(-1) by reserpine pretreatment. Following administering compound
      48/80, a mast cell degranulator, electrical field stimulation induced a dramatic
      increase of endogenous histamine release from isolated atria (303.57 +/-72.93 ng
      x ml(-1)). When compound 48/80 was added to the reserpine-treated atria, the
      release of histamine induced by field stimulation was decreased to 207.14 +/-
      76.39 ng x ml(-1). 4 These results provide novel evidence that histamine co
      exists with noradrenaline in sympathetic nerves and might act as a
      neurotransmitter to modulate sympathetic neurotransmission.

PMID- 15255819
TI  - The emerging role of pharmacogenetics: implications for clinical psychiatry.
AB  - OBJECTIVE: This article aims to review the implications of pharmacogenetics for
      clinical psychiatry; these are discussed in the context of environmental and
      sociocultural factors. METHOD: A selective literature review was conducted using
      Medline search and other relevant references available to the authors. RESULTS:
      The individual differences in therapeutic and adverse effects of psychotropic
      drugs are largely determined by genetic factors. Recent advances in
      pharmacogenetics have highlighted the potential utility in predicting metabolic
      phenotypes, risks for side-effects and likelihood of drug response for the
      individual patient. CONCLUSIONS: Genotyping, especially for drug metabolizing
      enzymes, could enable more rational, cost-effective and optimal prescribing in
      future psychopharmacotherapy. Although the advances of pharmacogenetics may have
      many benefits in clinical practice, the importance of non-genetic factors must
      also be considered as cultural and environmental factors significantly impinge on
      response to medications. To clarify the extent pharmacogenetics can be adopted in
      clinical practice to predict drug response in patients from diverse backgrounds,
      further studies in different ethnic groups and clinical settings are required.

PMID- 15255820
TI  - Vocational rehabilitation in psychiatry: a re-evaluation.
AB  - OBJECTIVE: To highlight the vocational gap in the provision of psychiatric
      rehabilitation, to outline the goals and conceptual framework of psychiatric
      rehabilitation, and to discuss rehabilitation interventions with specific
      reference to vocational rehabilitation and the evidence base for supported
      employment. CONCLUSIONS AND SERVICE IMPLICATIONS: Vocational psychiatric
      rehabilitation has been a neglected area of practice in Australian psychiatry.
      Psychiatric treatment needs to adopt a more balanced approach in the provision of
      a range of services, including vocational rehabilitation, in order to improve
      long-term outcomes for people suffering from psychiatric disability. A vocational
      focus should be included in psychiatric rehabilitation and better integration
      between mental health services and vocational services needs to take place.
      Supported employment is an evidence-based practice that is designed to help
      people with psychiatric disabilities participate as much as possible in the
      competitive job market.

PMID- 15255821
TI  - Psychiatric aspects of detention: illustrative case studies.
AB  - OBJECTIVE: Although the two political systems cannot be equated, the psychiatric
      and psychosocial issues raised by people detained under the migration regulations
      of the present Australian government, and those detained under the security
      legislation of the last apartheid government in South Africa, are similar in many
      aspects. METHOD: We present two case scenarios representative of the cumulative
      clinical experience of the authors in their work (as part of their routine
      clinical practice and medical school experience) with asylum seekers and
      political detainees in acute psychiatric units in both South Africa and
      Australia. RESULTS: Similar issues raised included the validity of a psychiatric
      diagnosis in these patients and the debate this conundrum provoked among the
      multidisciplinary teams. The pressures placed on clinicians by politicians in
      terms of clinical management of hospitalized detainees raised similar ethical
      questions across both countries. The clinical syndromes of depression and
      posttraumatic stress disorder were similar. The effect of the 'non-person' status
      conferred upon refugees by the 'temporary protection visa' could be equated with
      the effect of 'banning orders' imposed on opponents of the Apartheid regime.
      CONCLUSIONS: In South Africa, political detainees entered into the struggle
      expecting to face hardship and torture at the hands of the government of the
      time. Asylum seekers flee to Australia expecting support from a democratic system
      and generally had not prepared themselves for further incarceration and yet
      another political struggle. Despite this seemingly fundamental difference, the
      experiences of detainees across two very different political systems are
      remarkably similar.

PMID- 15255822
TI  - Cognitive functioning in young people with first episode psychosis: relationship
      to diagnosis and clinical characteristics.
AB  - OBJECTIVE: To examine the extent and nature of neuropsychological deficits in
      adolescents and young people with first episode psychosis (FEP), and to determine
      whether the pattern and extent of neuropsychological deficits varied according to
      diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy
      controls completed a comprehensive battery of neuropsychological tests, grouped
      into 10 cognitive domains. First episode psychosis subjects were stratified into
      three diagnostic groups (schizophrenia, affective disorders, substance-induced
      psychosis) and differences in cognitive profiles were examined. The contribution
      of demographic and clinical characteristics to cognitive performance was also
      explored. RESULTS: The schizophrenia group demonstrated significantly worse
      performance on tasks of verbal learning and memory than the affective disorders
      group. Compared to healthy controls, the schizophrenia group also demonstrated
      global impairment across the majority of cognitive domains. The substance-induced
      group's performance lay between that of the schizophrenia and affective disorders
      groups. Analyses of differential deficits revealed that verbal learning, verbal
      memory and current intellectual functioning were selectively impaired in the
      schizophrenia group, whereas the affective disorders group demonstrated a
      selective deficit in speeded processing. Premorbid intellectual functioning,
      negative symptomatology and medication levels were the strongest predictors of
      cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits
      differentiate individuals with schizophrenia from those with psychotic affective
      disorders. Although significant cognitive deficits are evident across all
      diagnostic FEP groups, individuals with schizophrenia appear to have more
      generalized impairment across a broad array of cognitive functions than other
      psychotic diagnoses. Lower premorbid intellectual functioning does not appear to
      contribute to greater cognitive deterioration following onset of psychosis, but
      severity of illness may be a more important factor than levels of mood
      disturbance.

PMID- 15255823
TI  - Assessing cost-effectiveness in mental health: family interventions for
      schizophrenia and related conditions.
AB  - OBJECTIVE: Existing evidence suggests that family interventions can be effective
      in reducing relapse rates in schizophrenia and related conditions. Despite this,
      such interventions are not routinely delivered in Australian mental health
      services. The objective of the current study is to investigate the incremental
      cost-effectiveness ratios (ICERs) of introducing three types of family
      interventions, namely: behavioural family management (BFM); behavioural
      intervention for families (BIF); and multiple family groups (MFG) into current
      mental health services in Australia. METHOD: The ICER of each of the family
      interventions is assessed from a health sector perspective, including the
      government, persons with schizophrenia and their families/carers using a
      standardized methodology. A two-stage approach is taken to the assessment of
      benefit. The first stage involves a quantitative analysis based on disability
      adjusted life years (DALYs) averted. The second stage involves application of
      'second filter' criteria (including equity, strength of evidence, feasibility and
      acceptability to stakeholders) to results. The robustness of results is tested
      using multivariate probabilistic sensitivity analysis. RESULTS: The most cost
      effective intervention, in order of magnitude, is BIF (8000 Australian dollars
      per DALY averted), followed by MFG (21,000 Australian dollars per DALY averted)
      and lastly BFM (28,000 Australian dollars per DALY averted). The inclusion of
      time costs makes BFM more cost-effective than MFG. Variation of discount rate has
      no effect on conclusions. CONCLUSIONS: All three interventions are considered
      'value-for-money' within an Australian context. This conclusion needs to be
      tempered against the methodological challenge of converting clinical outcomes
      into a generic economic outcome measure (DALY). Issues surrounding the
      feasibility of routinely implementing such interventions need to be addressed.

PMID- 15255824
TI  - Risk factors for suicide and other deaths following hospital treated self
      poisoning in Australia.
AB  - OBJECTIVE: To analyze the risk factors for suicide, premature death and all-cause
      death in a representative population of hospital-treated deliberate self
      poisoning patients. METHOD: A prospective cohort study using data-linkage between
      the Hunter Area Toxicology Service Database and the National Death Index of the
      Australian Institute of Health and Welfare, from January 1991 to December 2000.
      RESULTS: There were 4105 subjects, of whom 228 (5.6%) died, 122 (2.9%) by
      premature death and 58 (1.4%) by suicide. The probability of suicide after 10
      years follow-up was 2%. The adjusted hazard ratios (95% CI) for suicide were:
      'disorders usually diagnosed in infancy, childhood and adolescence', 5.28 (95% CI
      = 2.04-13.65): male gender, 4.25 (95% CI = 2.21-8.14); discharge to involuntary
      psychiatric hospital admission, 3.20 (95% CI = 1.78-5.76); and increasing age,
      1.02 (95% CI = 1.01-1.04). Men and women showed different patterns of
      multivariate risks, although increased risk with increasing age and discharge to
      an involuntary psychiatric admission was true for both. The standardized all
      cause mortality ratio (95% CI) was: for men, 6.42 (95% CI = 5.44-7.57), and for
      women 4.39 (95% CI = 3.56-5.41). The standardized suicide mortality ratio (95%
      CI) was: for men, 20.55 (95% CI = 15.24-27.73), and for women 22.95 (95% CI =
      13.82-38.11). CONCLUSIONS: Men and women have different risk factors for
      subsequent suicide after self-poisoning. Hospital-treated self-poisoning patients
      have increased risk of subsequent suicide, premature and all-cause death.
      Psychiatric assessment, leading to discharge decisions, is worthwhile in
      identifying patients at long-term risk of suicide, premature and all-cause death.

PMID- 15255825
TI  - Screening for depression in women with metastatic breast cancer: a comparison of
      the Beck Depression Inventory Short Form and the Hospital Anxiety and Depression
      Scale.
AB  - OBJECTIVE: To compare two self-report questionnaires for identifying possible
      depression in women with metastatic breast cancer. METHOD: We conducted
      structured psychiatric interviews and administered the Beck Depression Inventory
      Short Form (BDI-SF) and Hospital Anxiety and Depression Scale (HADS) to 227 women
      with stage IV breast cancer. The accuracy for identifying DSM-IV-defined major
      and minor depression was examined. Sensitivity, specificity, positive (PPV) and
      negative (NPV) predictive values were calculated and receiver operating
      characteristic curves plotted. RESULTS: Seventy-four (32.6%) patients satisfied
      DSM-IV criteria for a depressive disorder. With a cut-off of 4, the BDI-SF had a
      sensitivity of 0.84, specificity of 0.63, and PPV of 0.52. A cut-off of 11 on the
      HADS-Depression scale (HADS-D) resulted in sensitivity, specificity, and PPV of
      0.16, 0.97, and 0.75, respectively. For major depression alone, the BDI-SF with a
      cut-off of 5 had excellent sensitivity but poor PPV; the HADS, with a cut-off of
      7, had weak sensitivity and PPV. CONCLUSIONS: Overall, the two scales perform
      similarly in identifying major depression, while the BDI-SF is the more useful in
      screening for DSM-IV major or minor depression categories in this clinical group.

PMID- 15255826
TI  - Normative verbal and non-verbal memory test scores for Australian women aged 56
      67.
AB  - OBJECTIVE: To establish normative data for tests of verbal and non-verbal memory
      for midlife Australian-born women, and in so doing investigate factors which
      contribute to variation in test performance. METHOD: Two hundred and fifty-seven
      healthy women aged 56-67 years (mean age 60), who are participating in the
      Melbourne Women's Midlife Longitudinal Health Project, were administered two word
      list learning tasks, a story recall task (the East Boston Memory Test) and the
      Faces subtest from the Wechsler Memory Scale III as part of a larger
      neuropsychological battery. Word list learning tasks consisted of either 16
      semantically related words, derived from the California Verbal Learning Test II,
      or a list of 10 unrelated words. Mood was assessed by the Center for
      Epidemiological Studies Depression questionnaire. RESULTS: Education was
      significantly related to memory performance and there was a non-significant trend
      for test scores to decline with age. Mood was unrelated to test performance. A
      confirmatory factor analysis indicated a clear distinction between verbal and non
      verbal memory performances. Mean scores were stratified by education (less than
      12 years vs. 12 or more years) and age (56-59 vs. 60-67 years), and scaled
      normative data were constructed for all the tests. CONCLUSION: This study
      provides education-based normative data for tests of verbal and non-verbal memory
      for midlife Australian women. The establishment of population-based normative
      data will facilitate future investigations of ageing and dementia in Australian
      women.

PMID- 15255827
TI  - The portrayal of mental health and illness in Australian non-fiction media.
AB  - OBJECTIVE: To provide a detailed picture of the extent, nature and quality of
      portrayal of mental health/illness in Australian non-fiction media. METHOD: Media
      items were retrieved from Australian newspaper, television and radio sources over
      a 1-year period, and identifying/descriptive data extracted from all items.
      Quality ratings were made on a randomly selected 10% of items, using an
      instrument based on criteria in Achieving the Balance (a resource designed to
      promote responsible reporting of mental health/illness). RESULTS: Reporting of
      mental health/illness was common, with 4351 newspaper, 1237 television and 7801
      radio items collected during the study period. Media items most frequently
      focused on policy/program initiatives in mental health (29.0%), or on
      causes/symptoms/treatment of mental illnesses (23.9%). Stories about mental
      health issues in the context of crime were relatively uncommon, accounting for
      only 5.6% of items. Most media items were of good quality on eight of the nine
      dimensions; the exception was that details of appropriate help services were only
      included in 6.4% of items. CONCLUSIONS: In contrast to previous research, the
      current study found that media reporting of mental health/illness was extensive,
      generally of good quality and focused less on themes of crime and violence than
      may have been expected. This is encouraging, since there is evidence that
      negative media portrayal of mental health/illness can detrimentally affect
      community attitudes. However, there are still opportunities for improving media
      reporting of mental health/illness, which should be taken up in future media
      strategies.

PMID- 15255828
TI  - New Zealand's psychiatrist workforce: profile, recruitment and retention.
AB  - OBJECTIVE: New Zealand is suspected of sharing other countries' difficulties of
      having inadequate numbers of practising psychiatrists and attracting
      psychiatrists to work outside its main urban centres, but there is no
      contemporary data on the socio-demographic and professional practice profile of
      its psychiatrists. This paper highlights some interesting trends about New
      Zealand's psychiatric workforce. METHOD: A postal questionnaire was sent to all
      actively practising vocationally registered psychiatrists with a New Zealand
      mailing address requesting information about basic demographic data, professional
      training experiences, current professional status, practise intentions, why they
      chose to work where they do and what factors might influence them to leave for
      another region of New Zealand or overseas. RESULTS: Of the 277 doctors on the
      vocational register for psychiatry, 159 responded, giving a response rate of
      59.8%. Most psychiatrists were male (n = 102; 64.2%), European (n = 144; 90.6%),
      aged between 41 and 60 (69.2%), born overseas (n = 90; 56%), had English as their
      primary language (n = 142; 89.3%) and were in a long-term relationship with
      dependent children (n = 99; 62.3%). Nearly all (n = 149; 95%) did their
      psychiatry training in a metropolitan area and most (n = 108; 67.9%) held the
      Fellowship of the Royal Australian and New Zealand College of Psychiatry
      (FRANZCP). Most worked in a metropolitan area (n = 136; 85.5%) and either wholly
      or partly in the public sector (n = 145; 93%). Nearly one-quarter expected to
      retire over the next decade. Professional factors were rated more important as a
      reason for staying by metropolitan psychiatrists compared with their non
      metropolitan counterparts (p < 0.001). Psychiatrists who did not have an FRANZCP
      (57%vs. 27%, p = 0.05), those who had spent more than 50% of their professional
      life in New Zealand (86%vs. 74%, p = 0.02) or those who had obtained their
      primary medical degree outside New Zealand were more likely to be in non
      metropolitan areas (81%vs. 49%, p = 0.04). Metropolitan psychiatrists rated
      personal and social reasons more highly than non-metropolitan psychiatrists did
      for factors which might induce them to leave for another area, whereas
      professional development was ranked lower. CONCLUSIONS: This is the first
      contemporary study of New Zealand's psychiatric workforce and it highlights some
      interesting trends and has significant implications for those concerned with the
      recruitment and retention of psychiatrists. Further investigation is suggested,
      as a more complete picture of New Zealand's specialist psychiatric workforce
      would be gained by including psychiatrists who are not vocationally registered.

PMID- 15255829
TI  - Borderline personality disorder: attitudinal change following training.
AB  - OBJECTIVE: To assess the effect of a two-day training workshop on clinician
      attitudes to working with people with borderline personality disorder (BPD). The
      main goal of the workshop was to achieve positive change in the attitude of
      clinicians treating people with BPD in a public setting. The hypothesis
      underlying the intervention was that informing clinicians about current concepts
      of the diagnosis, aetiology, prognosis and treatment of BPD, combined with
      detailed discussion of the principles of treatment in the public setting, would
      result in positive attitude change. METHOD: Changes in attitudes (optimism,
      enthusiasm, confidence and willingness to work with people with BPD) and self
      perceptions of knowledge and skills among staff working with BPD patients were
      assessed for 418 participants from public mental health and substance abuse
      services who attended the workshops over an 18-month period. A survey
      questionnaire was administered pre- and post-workshop and at 6 month follow-up
      (time 1, time 2, time 3, respectively). One-way repeated measures analysis of
      variance (anova) were carried out to compare scores on attitudes and perceptions
      of knowledge and skills at time 1, time 2 and time 3. RESULTS: The results from
      repeated measures anova show that there was a statistically significant effect
      for time for all six items. Analyses of within-subject contrasts indicated that,
      for all six variables, the time 2 and the time 3 scores were statistically
      significantly different from time 1 scores (p < 0.01). These findings confirm
      that there were statistically significant changes at the post-workshop
      assessment, which were either maintained or showed a non-significant decrease at
      6-month follow-up. CONCLUSIONS: The brief training workshop described was
      effective in achieving positive attitude change in clinicians working with
      patients with BPD. This research shows that it is possible through brief training
      to assist clinician positivity and to effect clinician attitude change.
      Implications of this research could include the influencing of future training of
      clinicians in public mental health and substance abuse fields.

PMID- 15255830
TI  - Improvement of amisulpride-induced extrapyramidal symptoms with quetiapine.

PMID- 15255831
TI  - Possible manic potential of buprenorphine.

PMID- 15255832
TI  - Aripiprazole-induced rabbit syndrome.

PMID- 15255840
TI  - Aromatase inhibitors: possible future applications.
AB  - In premenopausal women ovaries are the major sites of estrogen production, while
      in postmenopausal women estrogen is produced by aromatization of ovarian and
      adrenal androgens in extragonadal sites, mostly in adipose tissue. Aromatase is a
      cytochrome P450 hemoprotein-containing enzyme complex that catalyzes the rate
      limiting step in the conversion of androstenedione and testosterone to estrone
      and estradiol (E2). Aromatase inhibitors (AIs) have been developed primarily for
      use in either natural or surgical postmenopausal patients. In premenopausal
      women, the ovary can overcome the estrogen blockade by reflex increments of
      luteinizing hormone (LH) and follicle stimulating hormone (FSH), so AIs must be
      combined with a gonadotropin releasing hormone (GnRH) agonist to prevent the
      reflex LH and FSH increments. In advanced hormone-dependent breast cancer
      treatment, AIs have been shown to be superior to tamoxifen. Preliminary evidence
      also suggests superiority in the adjuvant, neoadjuvant settings and also for
      breast cancer prevention. AIs have been used in infertility and can increase
      ovulation rate. Reducing FSH dose, estrogen levels, improving response to FSH,
      implantation rates, and developing multiple follicles that can be used in in
      vitro maturation procedures are potential areas that AIs might be used in in
      assisted reproductive technologies (ART), besides simple ovulation induction. AIs
      are reported to be successful in treatment of endometriosis, an estrogen
      dependent process. The use of AIs in gynecomastia, puberte precox, leiomyoma
      uteri, some estrogen-dependent cancers (ovarian), endometrial cancer and male
      infertility are reported; some of the results are promising but more clinical
      trials are needed. AIs are predicted to become the gold standard in the treatment
      of estrogen-dependent diseases in reproductive medicine in the near future.

PMID- 15255841
TI  - Elevated amniotic fluid leptin levels in early second trimester are associated
      with earlier delivery and lower birthweight in twin pregnancy.
AB  - OBJECTIVE: To explore the possibility of using early second trimester amniotic
      fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY
      DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second
      trimester were analyzed for their correlation with gestational age at delivery
      and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from
      small for gestational age (SGA) twin pregnancies were compared with those in 20
      amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A
      significant correlation was observed between amniotic fluid leptin levels and
      gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r
      = 0.72, p < 0.001). There was also a significant correlation between gestational
      age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average
      gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean
      birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were
      37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid
      leptin levels were found to be significantly higher ( p < 0.001) for women in the
      SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5
      ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester
      were associated with both lower gestational age at delivery and lower
      birthweight. Our results suggest that amniotic fluid leptin levels in early
      second trimester may be a good marker for the prediction of perinatal
      complications in twin pregnancy.

PMID- 15255842
TI  - Does fetal gender affect cytotrophoblast cell activity in the human term
      placenta? Correlation with maternal hCG levels.
AB  - BACKGROUND: Pregnant women with female fetuses have higher maternal serum human
      chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67,
      a cell proliferation and activity marker, is confined mostly in the nuclei of
      villous cytotrophoblasts of the human placenta. In this study, we examined the
      effect of fetal gender on the cytotrophoblast cell activity in human term
      placenta, with special regard to maternal serum and cord blood hCG levels.
      METHODS: Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17
      female fetuses) were recruited in the study. hCG was measured in maternal
      peripheral serum and umbilical cord blood. Placental samples were collected in
      each patient during the cesarean section. Cytotrophoblast cell activity was
      measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index
      values of the cytotrophoblasts were compared between the female and male
      placentas. RESULTS: Maternal serum and cord blood hCG levels were higher in
      pregnant women with female fetuses than in those carrying male fetuses. There was
      no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells.
      There was no correlation between maternal serum and cord blood hCG levels and Ki
      67 staining index values of the cytotrophoblast cells. CONCLUSIONS: The
      difference in maternal serum and cord blood hCG levels in correlation with the
      fetal gender is not associated with cytotrophoblast cell activity in the human
      term placenta. The gender of the fetus does not seem to affect the regulation of
      cytotrophoblast cell proliferation.

PMID- 15255843
TI  - Fetal age assessment based on ultrasound head biometry and the effect of maternal
      and fetal factors.
AB  - BACKGROUND: Maternal height and weight have increased during the past 20 years,
      as has birthweight. The aim of the present study was to establish new reference
      charts for gestational age (GA) assessment using fetal biparietal diameter (BPD)
      and head circumference (HC), and to determine the effect of maternal and fetal
      factors on age assessment. METHODS: This was a prospective, cross-sectional study
      of 650 healthy women with regular menstrual periods and singleton uncomplicated
      pregnancies, recruited after written consent. BPD (outer-outer) and HC were
      measured at 10-24 weeks of gestation. We used regression analysis to construct
      mean curves and assess the effect of maternal and fetal factors on age
      assessment. RESULTS: BPD and HC were successfully measured in 642 participants.
      Using BPD and HC before 20 weeks, the new charts gave 3-8 days higher GA
      assessment than the charts presently in use, and <1 day difference compared to
      other recently established charts. Maternal age, multiparity, fetal gender,
      breech position and shape of fetal head affect GA estimation by 1-2 days when
      using BPD (p = 0.0001-0.02). Only maternal age and fetal gender affected GA
      estimation when using HC (</= 1 day, p = 0.001). CONCLUSIONS: Our new charts for
      assessing gestational age based on fetal head biometry are notably different from
      charts presently in use. Maternal and especially fetal factors affect gestational
      age assessment when using BPD, but less so for the HC method, which is suggested
      as the more robust method.

PMID- 15255844
TI  - The decidual suction method: a new way of collecting decidual tissue for
      functional and morphological studies.
AB  - BACKGROUND: Studies of extravillous trophoblasts and placental bed spiral
      arteries are essential for a better understanding of pathological pregnancies
      such as preeclampsia, intrauterine growth restriction and diabetes mellitus. A
      major challenge is to obtain representative and sufficient tissue for
      morphological and functional investigations. Currently, tissue material is mostly
      harvested by placental bed biopsy (PBB). We describe a new suction method to
      obtain a larger volume of decidual tissue from the placental bed. METHODS: Tissue
      was harvested in 51 cesarean sections by vacuum suction of the placental bed.
      Sections from formalin-fixed, paraffin-embedded tissue were routinely stained
      with hematoxylin and eosin (H&E), immunostained with a panel of antibodies and
      morphologically examined for the presence of trophoblasts and spiral arteries.
      The results were compared with those from archive material from PBBs and
      placental basal plate sections (BPSs). Short-term adverse events were registered
      for the study patients. Long-term complications were registered from medical
      charts of 151 women having undergone the decidual suction method (DSM), with a
      follow-up of 38-60 months. RESULTS: In 86% (n = 44), one random section from the
      decidual suction material demonstrated at least one spiral artery. In 37% (n =
      19), six or more spiral arteries were present. All sections revealed extravillous
      trophoblasts. No short- or long-term morbidity was recorded. CONCLUSIONS: The
      decidual suction method represents an important improvement in the work to obtain
      sufficient decidual tissue for morphological and functional studies of
      extravillous trophoblast function and spiral artery adaptation. The method is
      safe, as no short- or long-term complications were registered.

PMID- 15255845
TI  - Treatment of fetal anemia due to red-cell alloimmunization with intrauterine
      transfusions in the Netherlands, 1988-1999.
AB  - OBJECTIVE: To assess pregnancy outcome after intrauterine transfusion (IUT) for
      fetal anemia due to red-cell alloimmunization in the Netherlands over 11 years,
      in order to improve care and counseling. METHODS: A retrospective cohort study
      was conducted from January 1, 1988, to January 1, 1999. Data were collected
      prospectively on all red-cell alloimmunized pregnancies requiring intrauterine
      blood transfusions. Primary outcome variables were fetal and neonatal survival in
      relation to the type of antibody, gestational age and presence or absence of
      hydrops. In addition, we studied short-term neonatal morbidity and procedure
      related complications. RESULTS: A total of 210 fetuses from 208 pregnancies
      received 593 transfusions. Overall survival rate was 86%. Survival of hydropic
      fetuses (78%) was significantly different from those without hydrops (92%). Low
      survival rates were especially found in hydropic fetuses with the first
      transfusion at gestational ages of 20 weeks or less (55%) or between 28 and 32
      weeks (59%). In maternal rhesus D [Rh(D)] immunization 89% of fetuses survived,
      whereas survival in the case of Kell immunization was 58%. All fetuses with
      anemia due to Rh(c) immunization survived. The overall fatal procedure-related
      complication rate was 1.7% per procedure, resulting in a fetal loss rate of 4.8%.
      CONCLUSIONS: Intrauterine intravascular transfusions are effective in the
      management of fetal alloimmune anemia. Fetal hydrops, mostly associated with late
      referral, decreases the chance of survival. To improve the outcome of red-cell
      alloimmunized pregnancies early diagnosis of fetal anemia and referral to a
      specialized center are important, enabling the start of treatment before hydrops
      develops.

PMID- 15255846
TI  - Anterior placenta percreta: surgical approach, hemostasis and uterine repair.
AB  - BACKGROUND: To describe an accurate approach, hemostatic procedures and uterine
      repair in patients with anterior placenta percreta. METHODS: A total of 68
      patients with anterior placenta percreta were included. A large retrovesical and
      parametrial dissection was performed in all cases. Hemostasis was achieved with
      selective vascular ligature or with surgical myometrial compression. The anterior
      wall defect was repaired using a myometrial suture, fibrin glue and polyglycolic
      mesh. Finally, a nonadherent cellulose layer was applied over this
      reconstruction. Hysteroscopy and T2 magnetic resonance imaging (MRI) were
      performed as a reconstruction control at 90 days after discharge. RESULTS:
      Elective surgery was performed in 49 patients and emergency surgery in 19. In 59
      midline incisions were performed and in nine lower transverse incisions. Forty
      nine patients underwent fundal hysterotomy and 19 transplacental segmental
      uterine approaches. The uteri of 50 patients with anterior placenta percreta were
      repaired. Of the 18 hysterectomies performed in this series, 16 were indicated
      due to massive destruction and two were secondary to coagulopathies. The
      following surgical complications developed: pelvic hemorrhage (one),
      coagulopathies (two), uterine infection (three), low ureteral ligations (two),
      iatrogenic foreign bodies (two) and collection (three). Uterine conservation was
      highly significant between the upper and lower invasion areas. Ten pregnancies
      were reported after the repair, resulting in uncomplicated cesarean delivery.
      CONCLUSION: This approach has allowed an adequate uterine repair in patients with
      anterior placenta percreta. Based on these results it is valid to assume that a
      functional and anatomic uterine repair has been successfully performed.

PMID- 15255847
TI  - Intentional cryopreservation of epididymal spermatozoa from percutaneous
      aspiration for dissociated intracytoplasmic sperm injection cycles.
AB  - BACKGROUND: To investigate the possibility of cryopreservation of spermatozoa
      obtained from percutaneous epididymal sperm aspiration (PESA) in patients with
      obstructive azoospermia and the feasibility of intentional dissociation of PESA
      and intracytoplasmic sperm injection (ICSI) cycles. METHODS: Fifty-six patients
      with obstructive azoospermia underwent diagnostic PESA before ovarian
      stimulation. If spermatozoa were found, they were frozen for subsequent ICSI. The
      outcome was compared with 17 fresh PESA/ICSI cycles. RESULTS: Among the 56
      patients, diagnostic PESA obtained spermatozoa in 51 patients. The mean motility
      of the spermatozoa decreased from 15.2% to 4.2% after freezing and thawing. These
      patients underwent 96 frozen PESA/ICSI cycles. The rates of fertilization,
      implantation and clinical pregnancy for frozen-thawed spermatozoa (71.6, 14.0 and
      40.6%, respectively) were similar to those for fresh spermatozoa (69.2, 13.2 and
      41.2%, respectively). CONCLUSIONS: Sufficient numbers of spermatozoa can be
      obtained for cryopreservation through PESA and the spermatozoa work well after
      thawing. The strategy of performing diagnostic PESA before ovarian stimulation
      and freezing the recovered spermatozoa for subsequent ICSI is feasible for
      patients with obstructive azoospermia.

PMID- 15255848
TI  - In vivo proton magnetic resonance spectroscopy in the evaluation of the
      endometrium.
AB  - BACKGROUND: The purposes of this study were to compare proton magnetic resonance
      (MR) spectroscopic evaluation of the endometrium with histology obtained by
      endometrial biopsy in women undergoing diagnostic curettage and to determine
      whether screening with MR spectroscopy (MRS) might be useful in the evaluation of
      the endometrium. METHODS: Twenty-three consecutive women who were scheduled for
      endometrial biopsy were included in the study. The women were evaluated by MRS,
      performed immediately before the endometrial biopsy. The MRS results were
      compared with the histological findings obtained from the endometrial biopsy.
      RESULTS: All of the cases were proven by pathological examination, and their
      diagnoses were secretory endometrium (11 cases), proliferative endometrium (seven
      cases) and disordered proliferative endometrium (five cases). The
      characteristically obtained signals of choline (Cho) and lipid were detected in
      all subjects in the secretory endometrium group. In the same group, eight
      patients showed lactate signals and six showed creatine (Cr) signals. In the
      disordered proliferative endometrium group, four patients showed lipid plus Cho
      signals. Two patients in the same group demonstrated both lactate and Cr signals.
      All patients in the proliferative endometrium group showed Cho signals, two
      patients demonstrated lactate plus Cho signals, and none of the patients in this
      group showed lipid and Cr signals. CONCLUSION: Proton magnetic resonance spectra
      can register certain metabolic differences in human endometrium in its different
      stages.

PMID- 15255849
TI  - Operation for pelvic organ prolapse: a follow-up study.
AB  - OBJECTIVE: Long-term results of surgery for pelvic organ prolapse in terms of
      objective and subjective cure rates, postoperative complications and side-effects
      were studied retrospectively. METHODS: Two hundred and sixty-nine women underwent
      surgery between 1986 and 1988 and were invited to a follow-up visit in 1998-99.
      One hundred and twenty-eight (47%) women attended the follow-up. In the time
      between surgery and follow-up, 67 (25%) women had died. The medical records were
      reviewed for women not attending follow-up (n = 131), revealing a higher age and
      a more severe prolapse in the lost to follow-up group. RESULTS: The subjective
      cure rate, with cure of all symptoms of pelvic organ prolapse, was 46% (n = 59).
      The objective cure rate, with satisfactory anatomic outcome, was 56% (n = 72). If
      perfect results had been attained in the women who did not undergo follow-up
      examination, the subjective and objective cure rates would be 73% and 79%,
      respectively. Previous prolapse surgery, a traumatic delivery, urinary
      incontinence and a prolapse stage III or more seemed to be risk factors for an
      adverse outcome. CONCLUSIONS: In evaluating the cure rate of pelvic floor surgery
      not only the anatomic outcome should be studied but also the outcome in terms of
      side-effects and/or symptoms as resolved, persistent or new onset. An
      unsatisfactory anatomic outcome was not necessarily associated with symptoms. The
      modest cure rate after surgery may be due to the aggravation with time of pelvic
      floor disorder, this confounding the results of surgery.

PMID- 15255850
TI  - Oral misoprostol vs. vaginal gemeprost prior to surgical termination of pregnancy
      in nulliparae.
AB  - BACKGROUND: To compare the efficacy and side-effects of intravaginal gemeprost
      with those of oral misoprostol for cervical ripening prior to first-trimester
      pregnancy termination in nulliparous women. METHODS: Retrospective analysis of
      surgical terminations of pregnancy performed before 90 days of gestation.
      Intravaginal gemeprost 1 mg or oral misoprostol 800 micro g was administered 2 h
      before the procedure. RESULTS: In total, 746 women were enrolled into the study,
      84 received intravaginal gemeprost and 662 oral misoprostol. Median baseline
      cervical dilatation was significantly greater in women who received misoprostol
      before the operation than in those who received gemeprost (7 mm vs. 3 mm; p <
      0.0001). The incidence of fever, vomiting and diarrhea was not different between
      the two groups. The incidence of abdominal pain with request for pain medication,
      emergency admission to operating room due to vaginal bleeding, hospital stay
      longer than 24 h and surgical repair of cervical injury due to Hegar dilatation
      was significantly higher among the gemeprost group than the misoprostol group.
      CONCLUSIONS: In cervical priming prior to first-trimester pregnancy termination
      in nulliparous women, oral misoprostol is more effective and is associated with
      fewer side-effects and complications than intravaginal gemeprost.

PMID- 15255851
TI  - Endometrial cancer within tamoxifen-related polyps in patients with breast
      cancer.

PMID- 15255852
TI  - The use of recombinant factor VIIa in severe postpartum hemorrhage.

PMID- 15255854
TI  - Choriocarcinoma presented as a vaginal tumor.

PMID- 15255853
TI  - Congenital cervical fibrosacroma with hydrops fetalis.

PMID- 15255855
TI  - Errors in the publication by Eskandar.

PMID- 15255859
TI  - The Fusarium wilt resistance locus Fom-2 of melon contains a single resistance
      gene with complex features.
AB  - The soil-borne fungus Fusarium oxysporum f.sp. melonis causes significant losses
      in the cultivated melon, a key member of the economically important family, the
      Cucurbitaceae. Here, we report the map-based cloning and characterization of the
      resistance gene Fom-2 that confers resistance to race 0 and 1 of this plant
      pathogen. Two recombination events, 75 kb apart, were found to bracket Fom-2
      after screening approximately 1324 gametes with PCR-based markers. Sequence
      analysis of the Fom-2 interval revealed the presence of two candidate genes. One
      candidate gene showed significant similarity to previously characterized
      resistance genes. Sequence analysis of this gene revealed clear polymorphisms
      between resistant and susceptible materials and was therefore designated as Fom
      2. Analysis of susceptible breeding lines (BL) presenting a haplotype very
      similar to the resistant cultivar MR-1 indicated that a gene conversion had
      occurred in Fom-2, resulting in a significant rearrangement of this gene. The
      second candidate gene which shared high similarity to an essential gene in
      Arabidopsis, presented an almost identical sequence in MR-1 and BL, further
      supporting Fom-2 identity. The gene conversion in Fom-2 produced a truncated R
      gene, revealing new insights into R gene evolution. Fom-2 was predicted to encode
      an NBS-LRR type R protein of the non-TIR subfamily. In contrast to most members
      of this class a coiled-coil structure was predicted within the LRR region rather
      than in the N-terminal. The Fom-2 physical region contained retroelement-like
      sequences and truncated genes, suggesting that this locus is complex.

PMID- 15255860
TI  - The ACR4 receptor-like kinase is required for surface formation of epidermis
      related tissues in Arabidopsis thaliana.
AB  - In higher plants, an outer layer of meristematic cells, the protoderm, forms
      early in embryogenesis and this layer gives rise to the epidermis in
      differentiating tissues. We proposed previously that an Arabidopsis thaliana
      homolog of crinkly4 (ACR4), a gene for a receptor-like protein kinase, would be
      involved in differentiation and/or maintenance of epidermis-related tissues. In
      the present study, we isolated loss-of-function acr4 mutants by a reverse genetic
      approach. Our extensive analyses using the transmission electron microscopy and
      the toluidine blue test -- a method that has recently been developed for the
      rapid visualization of defects in the leaf cuticle -- showed that the acr4
      mutations significantly affected the differentiation of leaf epidermal cells,
      suggesting similar roles for ACR4 and CR4 in the differentiation of leaf
      epidermis. Our acr4 mutants also had various abnormalities related to epidermal
      differentiation, which included disorganized cell layers in the integument and
      endothelium of ovules. In addition, the green fluorescent protein fused to ACR4
      was localized preferentially on the lateral and basal plasma membranes in the
      epidermis of the leaf primordia, suggesting a role for ACR4 in epidermal
      differentiation at cell surfaces that make contact with adjacent cells.
      Furthermore, the loss-of-function mutations in the ACR4 and ABNORMAL LEAF SHAPE1
      (ALE1) genes, which encode a putative subtilisin-like serine protease,
      synergistically affected the function of the epidermis such that most leaves
      fused. Thus, ACR4 seems to play an essential role in the differentiation of
      proper epidermal cells in both vegetative and reproductive tissues.

PMID- 15255861
TI  - Functional identification of rice syn-copalyl diphosphate synthase and its role
      in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural
      products.
AB  - Rice produces a number of phytoalexins, and at least one allelopathic agent, from
      syn-copalyl diphosphate (CPP), representing the only known metabolic fate for
      this compound. Thus, the class II terpene synthase that converts the universal
      diterpenoid precursor geranylgeranyl diphosphate to syn-CPP catalyzes the
      committed step in biosynthesis of these natural products. Here the extensive
      sequence information available for rice was coupled to recombinant expression and
      functional analysis to identify syn-copalyl diphosphate synthase (OsCPSsyn). In
      addition, OsCPSsyn mRNA was found to be specifically induced in leaves by
      conditions that stimulate phytoalexin biosynthesis. Therefore, transcription of
      OsCPSsyn seems to be an important regulatory point for controlling the production
      of these defensive compounds. Finally, alignments carried out with OsCPSsyn
      revealed that class II terpene synthases exhibit a sequence conservation pattern
      substantially different from that of the prototypical class I enzymes. One
      particularly notable feature is the specific conservation of the functionally
      cryptic 'insertional' sequence element in class II terpene synthases, indicating
      that this region is important for the corresponding cyclization reaction.

PMID- 15255862
TI  - Site-directed mutagenesis and protein 3D-homology modelling suggest a catalytic
      mechanism for UDP-glucose-dependent betanidin 5-O-glucosyltransferase from
      Dorotheanthus bellidiformis.
AB  - In livingstone daisy (Dorotheanthus bellidiformis), betanidin 5-O
      glucosyltransferase (UGT73A5) is involved in the regiospecific glucosylation of
      betanidin and various flavonols. Based on sequence alignments several amino acid
      candidates which might be essential for catalysis were identified. The selected
      amino acids of the functionally expressed protein, suggested to be involved in
      substrate binding and turnover, were substituted via site-directed mutagenesis.
      The substitution of two highly conserved amino acids, Glu378, located in the
      proposed UDP-glucose binding site, and His22, located close to the N-terminus,
      led to the complete loss of enzyme activity. A 3D model of this regiospecific
      betanidin and flavonoid glucosyltransferase was constructed and the active site
      modelled. This model was based on the crystallographic structure of a bacterial
      UDP-glucose-dependent glucosyltransferase from Amycolatopsis orientalis used as a
      template and the generated null mutations. To explain the observed inversion in
      the configuration of the bound sugar, semiempirical calculations favour an SN-1
      reaction, as one plausible alternative to the generally proposed SN-2 mechanism
      discussed for plant natural product glucosyltransferases. The calculated
      structural data do not only explain the abstraction of a proton from the acceptor
      betanidin, but further imply that the reaction mechanism might also involve a
      catalytic triad, with similarities described for the serine protease family.

PMID- 15255863
TI  - Roles of the AtErcc1 protein in recombination.
AB  - Summary Atercc1, the recently characterized Arabidopsis homologue of the Ercc1
      (Rad10) protein, is a key component of nucleotide excision repair as part of a
      structure-specific endonuclease which cleaves 5' to UV photoproducts in DNA. This
      endonuclease also acts in removing overhanging non-homologous DNA 'tails' in
      synapsed recombination intermediates. We have previously demonstrated this
      recombination function of the Arabidopsis thaliana Xpf homologue, AtRad1p, and
      show here that recombination between plasmid DNA substrates containing non
      homologous tails is specifically reduced 12-fold in atercc1 mutant plants
      compared with the wild type. Furthermore, using chromosomal tandem-repeat
      recombination substrates, we show that AtErcc1p is required for bleomycin
      induction of mitotic recombination in the chromosomal context. This work thus
      confirms both the specific and general recombination roles of the Atercc1 protein
      in recombination in Arabidopsis.

PMID- 15255864
TI  - LeSTIG1, an extracellular binding partner for the pollen receptor kinases LePRK1
      and LePRK2, promotes pollen tube growth in vitro.
AB  - As pollen tubes grow through the pistil they are thought to perceive and respond
      to diverse signals. The tomato pollen-specific receptor kinases LePRK1 and LePRK2
      might participate in signaling during pollen tube growth. We previously showed
      that the extracellular domain of LePRK2 interacts with a pollen protein, LAT52,
      before but not after pollen germination. To determine whether LePRK2 might have
      different binding partner(s) after pollen germination, we characterized two more
      proteins that, like LAT52, were identified in yeast two-hybrid screens using the
      extracellular domains of LePRK1 and LePRK2 as baits. We show that LeSHY, a
      leucine-rich repeat protein from pollen, and LeSTIG1, a small cysteine-rich
      protein from pistil, can bind the extracellular domains of both LePRK1 and LePRK2
      in vitro. In vitro binding assays with the extracellular domain of LePRK2
      suggested that LeSTIG1 could displace binding of LAT52, consistent with the idea
      that LePRK1 and LePRK2 might interact with different ligands at different stages
      of pollen tube growth. Exogenous LeSTIG1 promotes pollen tube growth in vitro.
      The interaction of these pollen kinases with LeSTIG1 supports the notion that
      LePRK1 and LePRK2 are involved in mediating pollen-pistil interactions.

PMID- 15255865
TI  - The chloroplastic protein translocation channel Toc75 and its paralog OEP80
      represent two distinct protein families and are targeted to the chloroplastic
      outer envelope by different mechanisms.
AB  - Toc75 is postulated to form the protein translocation channel in the
      chloroplastic outer envelope membrane. Proteins homologous to Toc75 are present
      in a wide range of organisms, with the closest homologs occurring in
      cyanobacteria. Therefore, an endosymbiotic origin of Toc75 has been postulated.
      Recently, a gene encoding a paralog to Toc75 was identified in Arabidopsis and
      its product was named atToc75-V. In the present study, we characterized this new
      Toc75 paralog, and investigated extensively the relationships among Toc75
      homologs from higher plants and bacteria in order to gain insights into the
      evolutionary origin of the chloroplastic protein translocation channel. First, we
      found that the native molecular weight of atToc75-V is 80 kDa and renamed it
      (AtOEP80) Arabidopsis thalianaouter envelope protein of 80 kDa. Second, we found
      that AtOEP80 and Toc75 utilize different mechanisms for their targeting to the
      chloroplastic envelope. Toc75 is directed with a cleavable bipartite transit
      peptide partly via the general import pathway, whereas AtOEP80 contains the
      targeting information within its mature sequence, and its targeting is
      independent of the general pathway. Third, we undertook phylogenetic analyses of
      Toc75 homologs from various organisms, and found that Toc75 and OEP80 represent
      two independent gene families that are most likely derived from cyanobacterial
      sequences. Our results suggest that Toc75 and OEP80 diverged early in the
      evolution of plastids from their common ancestor with modern cyanobacteria.

PMID- 15255866
TI  - TT2, TT8, and TTG1 synergistically specify the expression of BANYULS and
      proanthocyanidin biosynthesis in Arabidopsis thaliana.
AB  - Genetic analyses have demonstrated that together with TTG1, a WD-repeat (WDR)
      protein, TT2 (MYB), and TT8 (bHLH) are necessary for the correct expression of
      BANYULS (BAN). This gene codes for the core enzyme of proanthocyanidin
      biosynthesis in Arabidopsis thaliana seed coat. The interplays of TT2, TT8, and
      their closest MYB/bHLH relatives, with TTG1 and the BAN promoter have been
      investigated using a combination of genetic and molecular approaches, both in
      yeast and in planta. The results obtained using glucocorticoid receptor fusion
      proteins in planta strongly suggest that TT2, TT8, and TTG1 can directly activate
      BAN expression. Experiments using yeast two- and three-hybrid clearly
      demonstrated that TT2, TT8, and TTG1 can form a stable ternary complex.
      Furthermore, although TT2 and TT8 were able to bind to the BAN promoter when
      simultaneously expressed in yeast, the activity of the complex correlated with
      the level of TTG1 expression in A. thaliana protoplasts. In addition, transient
      expression experiments revealed that TTG1 acts mainly through the bHLH partner
      (i.e. TT8 or related proteins) and that TT2 cannot be replaced by any other
      related A. thaliana MYB proteins to activate BAN. Finally and consistent with
      these results, the ectopic expression of TT2 was sufficient to trigger BAN
      activation in vegetative parts, but only where TTG1 was expressed. Taken
      together, these results indicate that TT2, TT8, and TTG1 can form a ternary
      complex directly regulating BAN expression in planta.

PMID- 15255867
TI  - Plant growth-promoting rhizobacteria systemically protect Arabidopsis thaliana
      against Cucumber mosaic virus by a salicylic acid and NPR1-independent and
      jasmonic acid-dependent signaling pathway.
AB  - Arabidopsis thaliana ecotype Columbia plants (Col-0) treated with plant growth
      promoting rhizobacteria (PGPR) Serattia marcescens strain 90-166 and Bacillus
      pumilus strain SE34 had significantly reduced symptom severity by Cucumber mosaic
      virus (CMV). In some cases, CMV accumulation was also significantly reduced in
      systemically infected leaves. The signal transduction pathway(s) associated with
      induced resistance against CMV by strain 90-166 was determined using mutant
      strains and transgenic and mutant Arabidopsis lines. NahG plants treated with
      strains 90-166 and SE34 had reduced symptom severity indicating that the
      resistance did not require salicylic acid (SA). Strain 90-166 naturally produces
      SA under iron-limited conditions. Col-0 and NahG plants treated with the SA
      deficient mutant, 90-166-1441, had significantly reduced CMV symptom severity
      with reduced virus accumulation in Col-0 plants. Another PGPR mutant, 90-166
      2882, caused reduced disease severity in Col-0 and NahG plants. In a time course
      study, strain 90-166 reduced virus accumulation at 7 but not at 14 and 21 days
      post-inoculation (dpi) on the non-inoculated leaves of Col-0 plants. NahG and
      npr1-1 plants treated with strain 90-166 had reduced amounts of virus at 7 and 14
      dpi but not at 21 dpi. In contrast, no decrease in CMV accumulation occurred in
      strain 90-166-treated fad3-2 fad7-2 fad8 plants. These data indicate that the
      protection of Arabidopsis against CMV by strain 90-166 follows a signaling
      pathway for virus protection that is independent of SA and NPR1, but dependent on
      jasmonic acid.

PMID- 15255868
TI  - Endoplasmic reticulum-resident proteins are constitutively transported to
      vacuoles for degradation.
AB  - Soluble endoplasmic reticulum (ER)-resident proteins have very long lives because
      of their ER residency. This residency depends largely on ER-retrieval signals at
      their C-terminus. We examined the long-term destiny of endogenous ER-resident
      proteins, a lumenal binding protein (BiP) and a protein disulfide isomerase
      (PDI), with cultured cells of Arabidopsis. ER residents, in contrast to vacuolar
      proteinases, were considerably degraded in cells at the stationary phase. A
      subcellular fractionation analysis suggested that ER residents were transported
      into the vacuoles, which accumulated the residents lacking the ER-retrieval
      signals. We showed that the PDI located in the vacuoles had high mannose glycans,
      but not complex glycans, which suggested that the ER resident was transported to
      the vacuoles independent of the medial/trans-Golgi complex. To visualize the
      pathway of transport of ER-resident proteins, tobacco BY-2 cells were transformed
      with a chimeric gene encoding an ER-targeted green fluorescent protein (30 kDa
      GFP-HDEL). In the transformed cells at the stationary phase, GFP fluorescence was
      observed in the vacuoles. A subcellular fractionation revealed that a trimmed
      form of 27 kDa GFP was localized in the vacuoles. Treatment with E-64d, an
      inhibitor of papain-type cysteine proteinases that inhibits the degradation of
      GFP in the vacuoles, resulted in a stable accumulation of 27 kDa GFP in the
      vacuoles, even in the logarithmic phase. Our results suggest that endogenous ER
      residents are transported constitutively to the vacuoles by bypassing the Golgi
      complex and are then degraded.

PMID- 15255869
TI  - Arabidopsis Yellow Stripe-Like2 (YSL2): a metal-regulated gene encoding a plasma
      membrane transporter of nicotianamine-metal complexes.
AB  - The Yellow Stripe-Like (YSL) family of proteins has been identified based on
      sequence similarity to maize Yellow Stripe1 (YS1), the transporter responsible
      for the primary uptake of iron from the soil. YS1 transports iron that is
      complexed by specific plant-derived Fe(III) chelators called phytosiderophores
      (PS). Non-grass species of plants neither make nor use PS, yet YSL family members
      are found in non-grass species (monocot, dicot, gymnosperm, and moss species)
      including Arabidopsis thaliana. YSLs in non-grasses have been hypothesized to
      transport metals complexed by nicotianamine (NA), an iron chelator that is
      structurally similar to PS and which is found in all higher plants. Here we show
      that Arabidopsis YSL2 (At5g24380) transports iron and copper when these metals
      are chelated by NA. YSL2 is expressed in many cell types in both roots and
      shoots, suggesting that diverse cell types obtain metals as metal-NA complexes.
      YSL2 transcription is regulated by the levels of iron and copper in the growth
      medium. Based on its expression pattern, a major function of the YSL2 appears to
      be in the lateral movement of metals in the vasculature.

PMID- 15255870
TI  - OsYSL2 is a rice metal-nicotianamine transporter that is regulated by iron and
      expressed in the phloem.
AB  - We identified 18 putative yellow stripe 1 (YS1)-like genes (OsYSLs) in the rice
      genome that exhibited 36-76% sequence similarity to maize iron(III)
      phytosiderophore transporter YS1. Of particular interest was OsYSL2, the
      transcripts of which were not detected in the roots of either iron-sufficient or
      iron-deficient plants, but dramatic expression was induced in the leaves by iron
      deficiency. Based on the nucleotide sequence, OsYSL2 was predicted to encode a
      polypeptide of 674 amino acids containing 14 putative transmembrane domains.
      OsYSL2:green fluorescent protein (GFP) was localized in the plasma membrane of
      onion epidermal cells. Promoter:beta-glucuronidase (GUS) analysis revealed that
      OsYSL2 was expressed in companion cells in iron-sufficient roots. GUS activity
      was increased in companion cells, but no GUS staining was observed in epidermal
      or cortex cells, even in iron-deficient roots. In the leaves and leaf sheaths of
      iron-sufficient rice, GUS staining was observed in phloem cells of the vascular
      bundles. In iron-deficient leaves, the OsYSL2 promoter was active in all tissues
      with particularly strong GUS activity evident in companion cells. The phloem
      specific expression of the OsYSL2 promoter suggests that OsYSL2 is involved in
      the phloem transport of iron. Strong OsYSL2 promoter activity was also detected
      in developing seeds. Electrophysiological measurements using Xenopus laevis
      oocytes showed that OsYSL2 transported iron(II)-nicotianamine (NA) and
      manganese(II)-NA, but did not transport iron(III)-phyosiderophore. These results
      suggest that OsYSL2 is a rice metal-NA transporter that is responsible for the
      phloem transport of iron and manganese, including the translocation of iron and
      manganese into the grain.

PMID- 15255871
TI  - Two genes encoding Arabidopsis halleri MTP1 metal transport proteins co-segregate
      with zinc tolerance and account for high MTP1 transcript levels.
AB  - The zinc hyperaccumulator plant Arabidopsis halleri is able to naturally
      accumulate 100-fold higher leaf zinc concentrations when compared with non
      accumulator species such as the closely related A. lyrata and A. thaliana,
      without showing toxicity symptoms. A novel member of the cation diffusion
      facilitator (CDF) protein family, an A. halleri metal tolerance protein 1 (MTP1),
      and the homologous A. thaliana Zn transporter (ZAT)/AtMTP1 metal-specifically
      complement the zinc hypersensitivity of a Saccharomyces cerevisiae zrc1 cot1
      mutant strain. A fusion of the AhMTP1 protein to green fluorescent protein (GFP)
      localizes to the vacuolar membrane of A. thaliana protoplasts. When compared with
      A. lyrata and A. thaliana, the total MTP1 transcript levels are substantially
      higher in the leaves and upregulated upon exposure to high zinc concentrations in
      the roots of A. halleri. The high MTP1 transcript levels in A. halleri can be
      primarily attributed to two genetically unlinked genomic AhMTP1 gene copies. The
      two corresponding loci co-segregate with zinc tolerance in the back-cross 1
      generation of a cross between the zinc-tolerant species A. halleri and the zinc
      sensitive species A. lyrata. In contrast, a third MTP1 gene in the genome of A.
      halleri generates only minor amounts of MTP1 transcripts and does not co
      segregate with zinc tolerance. Our data suggests that zinc tolerance in A.
      halleri involves an expanded copy number of an ancestral MTP1 gene, encoding
      functional proteins that mediate the detoxification of zinc in the cell vacuole.
      At the transcript level, MTP1 gene copies of A. halleri are regulated
      differentially and in response to changes in zinc supply.

PMID- 15255872
TI  - Stable high-level transgene expression in Arabidopsis thaliana using gene
      silencing mutants and matrix attachment regions.
AB  - Basic and applied research involving transgenic plants often requires consistent
      high-level expression of transgenes. However, high inter-transformant variability
      of transgene expression caused by various phenomena, including gene silencing, is
      frequently observed. Here, we show that stable, high-level transgene expression
      is obtained using Arabidopsis thaliana post-transcriptional gene silencing (PTGS)
      sgs2 and sgs3 mutants. In populations of first generation (T1) A. thaliana plants
      transformed with a beta-glucuronidase (GUS) gene (uidA) driven by the 35S
      cauliflower mosaic virus promoter (p35S), the incidence of highly expressing
      transformants shifted from 20% in wild type background to 100% in sgs2 and sgs3
      backgrounds. Likewise, when sgs2 mutants were transformed with a cyclin-dependent
      kinase inhibitor 6 gene under control of p35S, all transformants showed a clear
      phenotype typified by serrated leaves, whereas such phenotype was only observed
      in about one of five wild type transformants. p35S-driven uidA expression
      remained high and steady in T2 sgs2 and sgs3 transformants, in marked contrast to
      the variable expression patterns observed in wild type T2 populations. We further
      show that T-DNA constructs flanked by matrix attachment regions of the chicken
      lysozyme gene (chiMARs) cause a boost in GUS activity by fivefold in sgs2 and 12
      fold in sgs3 plants, reaching up to 10% of the total soluble proteins, whereas no
      such boost is observed in the wild type background. MAR-based plant
      transformation vectors used in a PTGS mutant background might be of high value
      for efficient high-throughput screening of transgene-based phenotypes as well as
      for obtaining extremely high transgene expression in plants.

PMID- 15255873
TI  - High throughput T-DNA insertion mutagenesis in rice: a first step towards in
      silico reverse genetics.
AB  - A library of 29,482 T-DNA enhancer trap lines has been generated in rice cv.
      Nipponbare. The regions flanking the T-DNA left border from the first 12,707
      primary transformants were systematically isolated by adapter anchor PCR and
      sequenced. A survey of the 7480 genomic sequences larger than 30 bp (average
      length 250 bp), representing 56.4% of the total readable sequences and matching
      the rice bacterial artificial chromosome/phage artificial chromosome (BAC/PAC)
      sequences assembled in pseudomolecules allowed the assigning of 6645 (88.8%) T
      DNA insertion sites to at least one position in the rice genome of cv.
      Nipponbare. T-DNA insertions appear to be rather randomly distributed over the 12
      rice chromosomes, with a slightly higher insertion frequency in chromosomes 1, 2,
      3 and 6. The distribution of 723 independent T-DNA insertions along the
      chromosome 1 pseudomolecule did not differ significantly from that of the
      predicted coding sequences in exhibiting a lower insertion density around the
      centromere region and a higher density in the subtelomeric regions where the gene
      density is higher. Further establishment of density graphs of T-DNA inserts along
      the recently released 12 rice pseudomolecules confirmed this non-uniform
      chromosome distribution. T-DNA appeared less prone to hot spots and cold spots of
      integration when compared with those revealed by a concurrent assignment of the
      Tos17 retrotransposon flanking sequences deposited in the National Center for
      Biotechnology Information (NCBI). T-DNA inserts rarely integrated into repetitive
      sequences. Based on the predicted gene annotation of chromosome 1, preferential
      insertion within the first 250 bp from the putative ATG start codon has been
      observed. Using 4 kb of sequences surrounding the insertion points, 62% of the
      sequences showed significant similarity to gene encoding known proteins (E-value
      < 1.00 e(-05)). To illustrate the in silico reverse genetic approach,
      identification of 83 T-DNA insertions within genes coding for transcription
      factors (TF) is presented. Based both on the estimated number of members of
      several large TF gene families (e.g. Myb, WRKY, HD-ZIP, Zinc-finger) and on the
      frequency of insertions in chromosome 1 predicted genes, we could extrapolate
      that 7-10% of the rice gene complement is already tagged by T-DNA insertion in
      the 6116 independent transformant population. This large resource is of high
      significance while assisting studies unravelling gene function in rice and
      cereals, notably through in silico reverse genetics.

PMID- 15255874
TI  - Application of a high-throughput HPLC-MS/MS assay to Arabidopsis mutant
      screening; evidence that threonine aldolase plays a role in seed nutritional
      quality.
AB  - Beyond their essential function as the building blocks of proteins, amino acids
      contribute to many aspects of plant biochemistry and physiology. Despite this,
      there are relatively large gaps in our understanding of the biochemical pathways
      and regulation of amino acid synthesis in plants. A rapid (1.5 min versus 20-90
      min for standard methods) HPLC-MS/MS assay for separating 19 amino acids was
      developed for quantifying levels of free amino acids in plant tissue. This assay
      was used to determine the free amino acid content in the seeds of 10,000 randomly
      mutagenized Arabidopsis lines, and 322 Arabidopsis lines with increased levels of
      one or more amino acids were identified. The heritability of the mutant phenotype
      was confirmed for 43 lines with increased seed levels of the aspartate-derived
      amino acids Ile, Lys, Thr, or Met. Genetic mapping and DNA sequencing identified
      a mutation in an Arabidopsis threonine aldolase (AT1G08630, EC 4.1.2.5) as the
      cause of increased seed Thr levels in one mutant. The assay that was developed
      for this project has broad applicability to Arabidopsis and other plant species.

PMID- 15255876
TI  - Medical arithmetick.

PMID- 15255877
TI  - Influence of inter-pregnancy interval on preterm delivery.
AB  - The influence of pregnancy spacing on preterm delivery (<37 weeks gestation) was
      examined in a group of mothers attending three Maternal and Child Health centres
      in three different districts in the city of Alexandria, Egypt between October
      2001 and July 2002. All pregnant mothers attending the centres were interviewed
      or had their medical records reviewed. They were followed up until delivery and
      were questioned about current and past obstetric history and their medical
      history; their haemoglobin level was measured. The inter-pregnancy interval was
      calculated as the number of months between the delivery date of the women's last
      previous live infant and the date of the last menstrual period before the current
      pregnancy. There were 1202 pregnant women eligible for inclusion. The inter
      pregnancy intervals were divided into five categories: <12, 12-36, 37-48, 49-60
      and >60 months. We calculated the rates of preterm deliveries for each inter
      pregnancy interval. Unadjusted odds ratios were estimated and stepwise logistic
      regression analysis was then used to adjust for all confounding factors. The rate
      of preterm delivery was 9.4%, and the lowest risk occurred in women who had an
      inter-pregnancy interval >60 months; 7.3% of those women gave birth to preterm
      infants. The rate of preterm delivery increased with increasing inter-pregnancy
      interval until 49-60 months; however, the association between inter-pregnancy
      interval and preterm delivery was not statistically significant whether using the
      crude or adjusted odds ratios.

PMID- 15255878
TI  - Association between severe nausea and vomiting in pregnancy and lower rate of
      preterm births.
AB  - Nausea and vomiting in pregnancy has been associated with some reduction in
      miscarriage in other studies. However the relationship between nausea and
      vomiting during pregnancy and preterm birth/low birthweight in newborns is
      inconsistent; therefore the objective of the study was to clarify this possible
      association. The population-based large control (without any defects) data set of
      the Hungarian Case-Control Surveillance System of Congenital Abnormalities was
      evaluated. Of 38,151 controls, 3869 (10.1%) had medically recorded and treated
      nausea and vomiting during pregnancy. The proportion of mothers who later
      delivered girls was higher in this group. Mothers with nausea and vomiting in
      pregnancy had a somewhat (0.3 week) longer gestational age and a lower proportion
      of preterm births (6.4% vs. 9.5%). This finding may be connected with the
      favourable hormonal milieu (larger placenta, higher level of chorionic
      gonadotrophin and oestrogens) of pregnant women with nausea and vomiting.

PMID- 15255879
TI  - Partner violence during pregnancy and risk of adverse pregnancy outcomes.
AB  - The purpose of this cross-sectional study was to investigate the association
      between partner physical or emotional abuse during pregnancy and pregnancy
      outcomes including perinatal death, low birthweight and preterm delivery. Women,
      aged 18-65, who attended one of two large primary care practices from 1997-98
      were recruited for this study. Ever pregnant women were asked the frequency of
      abuse during each pregnancy and details of the pregnancy outcomes. Information
      regarding abuse during pregnancy and pregnancy outcomes was available for 755
      women surveyed who reported a live birth or late fetal death, 14.7% indicated
      that an intimate partner was violent or abusive toward them during a pregnancy
      (274 of 1862 pregnancies). Abuse during pregnancy was significantly associated
      with an increased risk of perinatal death (adjusted relative risk [aRR] = 2.1,
      95% confidence interval [CI] 1.3, 3.4) and, among live births, with preterm low
      birthweight (aRR = 2.4; 95% CI 1.5, 4.0) and term low birthweight (aRR = 1.9; 95%
      CI 1.0, 3.4). Greater abuse frequency was associated with increased risk. Abuse
      during pregnancy was associated with perinatal deaths and preterm low birthweight
      deliveries.

PMID- 15255880
TI  - Choosing the best estimate of gestational age from routinely collected population
      based perinatal data.
AB  - Obtaining gestational data of acceptable validity on whole populations is a
      considerable challenge, which must be met in order to further epidemiological
      investigation involving perinatal factors. As the means of estimating gestational
      duration multiply, routinely available population data pertaining to gestational
      duration may be conflicting. This exacerbates its reputation for unreliability,
      which is due primarily to the generally occult nature of conception and secondly
      to the propensity for data entry errors of the data from which gestational
      duration is estimated. However, the key to improving reliability may
      paradoxically lie in the increasing variety of methods for estimating gestational
      duration, because agreement between independent observations increases the
      reliability that can be placed on estimates of factors that are inherently
      difficult to measure. This paper demonstrates that the acceptability of
      population data for gestational duration can be improved by simple rectification
      of recurring data entry errors and demanding compatibility of two independent
      estimates of gestational duration. Compared with the previous algorithm that
      relied primarily on last menstrual period data, the new algorithm, that considers
      both antenatal and neonatal indicators of gestational duration, decreased the
      proportion of births in a geographically defined birth cohort 1986-99 (n=354,216)
      without a gestational estimate, from 0.5% to 0.03%, halved the number of births
      of >400 g estimated to occur before 20 weeks, and almost eliminated gestational
      estimates of >45 weeks.

PMID- 15255881
TI  - Trends in neural tube defects in Western Australia in Indigenous and non
      Indigenous populations.
AB  - Neural tube defects (NTD) were 43% more common in Indigenous than in non
      Indigenous infants in Western Australia in the 1980s, and there has been a fall
      in NTD overall in Western Australia since promotion of folate and voluntary
      fortification of food has occurred. In order to investigate whether the fall had
      occurred in both indigenous and non-Indigenous infants, data on NTD (births and
      terminations) were obtained from the WA Birth Defects Registry, and on all births
      from the Maternal and Child Health Research Data Base. Knowledge of folate was
      asked in a survey of indigenous women interviewed postpartum. Before the
      promotion of folate (1980-92), there has been a 42% increase in NTD in Indigenous
      compared with non-Indigenous infants (prevalence ratio (PR)=1.42 [95% confidence
      interval (CI) 1.04, 1.94]); while in the most recent period (1996-2000), the
      prevalence in Indigenous infants was almost twice that of non-Indigenous infants
      (PR 1.98 [CI 1.25, 3.15]). Fifty-five per cent of Indigenous women knew about
      folate in pregnancy. Similar to sudden infant death syndrome, this study has
      highlighted health promotion that has been successful in reducing the risk of a
      childhood condition overall, but has failed to be effective for Indigenous
      children.

PMID- 15255882
TI  - A prospective association between cocoon use in infancy and childhood asthma.
AB  - There is increasing evidence for a role for bedding items in the development of
      asthma. The use of some forms of synthetic bedding, such as foam mattresses and
      pillows, is associated with a significantly increased risk of childhood wheeze.
      Our aim was to examine prospectively whether the use of synthetic cocoon/baby
      nests in infancy is associated with the subsequent development of wheeze in
      childhood. Data collected in 1988 as part of the Tasmanian Infant Health Survey
      were linked to the cross-sectional Childhood Asthma Survey conducted in 1995 in
      Tasmania, Australia. We were able to match 863 records out of the 1111 in the
      1988 survey. Information including parental, child-care, and the infant's
      sleeping environment was collected at home interview in 1988 when the infant was
      1 month of age. Data including sleep environment and asthma symptoms were
      available for each child at age 7 years. A generalised linear model was used to
      calculate the adjusted relative risk (RR) estimates for symptoms of wheeze and
      infant cocoon use. For children who were placed in a cocoon in infancy, there was
      an increased risk of recent wheeze (adjusted RR = 4.33 [95% CI 2.08, 9.02]) and
      night wheeze (adjusted RR = 3.35 [95% CI 1.52, 7.39]) at age 7 years. In view of
      the increasing prevalence of childhood asthma, the identification of potentially
      modifiable environmental factors which might operate in infancy is of importance.
      The present findings implicate infant bedding choice as a significant factor and
      further studies on the infant sleeping environment are indicated.

PMID- 15255883
TI  - Transition from Birth to Ten to Birth to Twenty: the South African cohort reaches
      13 years of age.
AB  - Birth to Ten now Birth to Twenty (BT20), is the largest and longest running
      longitudinal birth cohort study in Africa. In this paper, the methods, magnitude
      and significance of recruitment, follow-up and attrition are described. Although
      more than 5000 births were notified in the area in the 7-week enrollment period
      in early 1990, only 3275 children were established to have been born to women who
      were residents in the Greater Johannesburg Metropolitan area for at least the
      first 6 months of the child's life. Seventy per cent of these children and their
      families have been followed up for more than 12 years, indicating an average
      attrition rate of less than 3% per annum, with most attrition occurring in the
      first 2 years of the study. The most common reason for attrition was movement out
      of the study area, although detailed follow-up, and the extent of contact re
      established at later points, indicate very high levels of circular migration
      among women and young children between urban and rural areas, as well as very
      high levels of residential mobility within urban areas. There has been no
      differential loss of vulnerable families and children. African women living in
      Soweto are the most consistent participants in the study. A bias, by population
      group membership and residential area, was introduced in the recruitment phases
      of the project by the difficulty of enrolling the small proportion of people in
      the metropolis, largely Whites, who used private delivery services in 1989-90.

PMID- 15255884
TI  - The Walker Project: a longitudinal study of 48,000 children born 1952-1966 (aged
      36-50 years in 2002) and their families.
AB  - The Walker cohort is a database of over 48,000 birth records that has recently
      become available. It contains meticulously recorded details of pregnancy, labour,
      birth and care before discharge for babies born in hospital in Dundee, Scotland
      between 1952 and 1966. These babies accounted for 75% of all births in Dundee at
      this time. Over 34,000 (73%) of these subjects can be identified and this
      presents the opportunity to link this birth information with a large number of
      current health-outcome databases covering both primary and secondary care.
      Further, it allows linkage of records across siblings and over two and, in
      future, three generations. The number of birth records available and linkage to
      current databases make this a unique birth cohort with huge potential for the
      investigation of the fetal origins of adult disease.

PMID- 15255886
TI  - Glycosomes: parasites and the divergence of peroxisomal purpose.
AB  - Peroxisomes are membrane-bounded organelles that compartmentalize a variety of
      metabolic functions. Perhaps the most divergent peroxisomes known are the
      glycosomes of trypanosomes and their relatives. The glycolytic pathway of these
      organisms resides within the glycosome. The development of robust molecular
      genetic and proteomic approaches coupled with the completion of the genome
      sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania
      major provides an opportunity to determine the complement of proteins within the
      glycosome and the function of compartmentation. Studies now suggest that
      regulation of glycolysis is a strong driving force for maintenance of the
      glycosome.

PMID- 15255887
TI  - Rafts and sphingolipid biosynthesis in the kinetoplastid parasitic protozoa.
AB  - Summary relatively large rafts are a feature of activated mammalian cells. These
      studies allow us to consider the functional role of lipid rafts in kinetoplastid
      parasites, which are particularly rich in lipid-anchored surface molecules.
      Morphological, biochemical and genetic studies indicate that lipid rafts (and
      sphingolipid biosythesis) are important in the differentiation of extracellular
      Leishmania to mammalian-infective metacyclic promastigotes, perhaps orchestrating
      the clearly observable reorganization of the plasma membrane during this process
      that leads to an activated metacyclic primed for invasion. However, the first
      step in the sphingolipid biosynthetic pathway (mediated by serine
      palmitoyltransferase), and at least regulated, de novo sphingoid base and
      ceramide synthesis, are not essential for the pathogenesis of intramacrophage
      Leishmania amastigotes.

PMID- 15255888
TI  - Endocytosis, membrane recycling and sorting of GPI-anchored proteins: Trypanosoma
      brucei as a model system.
AB  - In the flagellated protozoon Trypanosoma brucei, endo- and exocytosis are
      restricted to a small area of the plasma membrane, the flagellar pocket. All
      endosomal compartments and the single Golgi complex are located within the
      posterior part of the cell between the flagellar pocket and the nucleus. The use
      of reverse genetic tools, including RNA interference, in combination with
      quantitative 3D-fluorescence and electron microscopic techniques has provided an
      insight into endosomal membrane traffic, which occurs at a very high rate and
      appears to exhibit a lower level of complexity than in mammalian cells. The
      flagellate is an excellent model system for studies on endocytosis, sorting and
      recycling of glycosylphosphatidylinositol-anchored glycoproteins, because 10(7)
      molecules of the variant surface glycoprotein form a dense coat at the cell's
      surface. Because the endocytic rate varies widely at different stages in the
      parasite's life cycle, trypanosomes may be used for investigating developmental
      aspects of their endocytic system.

PMID- 15255889
TI  - Light matters: phototaxis and signal transduction in unicellular cyanobacteria.
AB  - Many photosynthetic microorganisms have evolved the ability to sense light
      quality and/or quantity and can steer themselves into optimal conditions within
      the environment. Phototaxis and gliding motility in unicellular cyanobacteria
      require type IV pili, which are multifunctional cell surface appendages. Screens
      for cells exhibiting aberrant motility uncovered several non-motile mutants as
      well as some that had lost positive phototaxis (consequently, they were
      negatively phototactic). Several negatively phototactic mutants mapped to the
      tax1 locus, which contains five chemotaxis-like genes. This locus includes a gene
      that encodes a putative photoreceptor (TaxD1) for positive phototaxis. A second
      chemotaxis-like cluster (tax3 locus) appears to be involved in pilus biogenesis.
      The biosynthesis and regulation of type IV pilus-based motility as well as the
      communication between the pilus motor and photosensory molecules appear to be
      complex and tightly regulated. Furthermore, the discovery that cyclic AMP and
      novel gene products are necessary for phototaxis/motility suggests that there
      might be additional levels of communication and signal processing.

PMID- 15255890
TI  - Chemical communication in proteobacteria: biochemical and structural studies of
      signal synthases and receptors required for intercellular signalling.
AB  - Cell-cell communication via the production and detection of chemical signal
      molecules has been the focus of a great deal of research over the past decade.
      One class of chemical signals widely used by proteobacteria consists of N-acyl
      homoserine lactones, which are synthesized by proteins related to LuxI of Vibrio
      fischeri and are detected by proteins related to the V. fischeri LuxR protein. A
      related marine bacterium, Vibrio harveyi, communicates using two chemical
      signals, one of which, autoinducer-2 (AI-2), is a furanone borate diester that is
      synthesized by the LuxS protein and detected by a periplasmic protein called
      LuxP. Evidence from a number of laboratories suggests that AI-2 may be used as a
      signal by diverse groups of bacteria, and might permit intergeneric signalling.
      These two families of signalling systems have been studied from the perspectives
      of physiology, ecology, biochemistry, and more recently, structural biology.
      Here, we review the biochemistry and structural biology of both acyl-homoserine
      lactone-dependent and AI-2-dependent signalling systems.

PMID- 15255891
TI  - What functions do linker histones provide?
AB  - Linker histones have long been known to facilitate chromatin condensation in
      vitro. For many years, this activity led to speculation that these proteins
      function as global repressors of transcription. However, work from numerous
      systems has demonstrated that this is not the case, and that linker histones
      appear to affect only the transcription of a small subset of genes, and, in fact,
      act to activate as well as repress transcription. Furthermore, there is evidence
      that suggests that linker histones are not required for mitotic condensation. In
      this review, we focus on studies of biological functions of linker histones
      primarily performed in unicellular eukaryotes. We highlight recent developments
      pointing towards linker histone involvement in DNA repair and ageing, which raise
      the possibility that the biological functions of linker histones are more varied
      than previously imagined.

PMID- 15255892
TI  - Activity reversal of Tet repressor caused by single amino acid exchanges.
AB  - We explore by extensive mutagenesis regions in the sequence allowing reversal of
      the allosteric response of Tet repressor. The wild type requires
      anhydrotetracycline for induction. About 100 mutants are presented, which, in
      contrast, require the drug for repression. Their mutations are clustered at the
      interface of the DNA- and inducer-binding domains. This interface consists of a
      central hydrophobic region surrounded by several hydrogen bonds. While most of
      the mutants described here contain two to five mutations, we found five positions
      in this region of TetR, at which single amino acid exchanges lead to activity
      reversal. They may disrupt the hydrogen-bonding network bordering the domain
      interface. We assume that the mutations cause a repositioning of the DNA reading
      head with respect to the effector binding core so that the same conformational
      change can result in opposite activities.

PMID- 15255893
TI  - Identification of activating region (AR) of Escherichia coli LysR-type
      transcription factor CysB and CysB contact site on RNA polymerase alpha subunit
      at the cysP promoter.
AB  - CysB is a LysR-type transcriptional regulator (LTTR) controlling the expression
      of numerous genes involved in bacterial sulphur assimilation via cysteine
      biosynthesis. Our previous mutational analysis of CysB identified several
      residues within the N-terminal domain crucial for DNA-binding function. Here, we
      focus on the functional significance of CysB residues localized in the turn
      between the alpha2 and alpha3 helices forming an N-terminal helix-turn-helix
      motif. On the basis of the characteristics of alanine-substituted mutants, we
      propose that CysB residues Y27, T28 and S29, lying in this turn region, comprise
      an 'activating region' (AR) that is crucial for positive control of the cysP
      promoter, but not for DNA binding and inducer response activities of CysB. Using
      a library of alanine substitutions in the C-terminal domain of the RNAP alpha
      subunit (alpha-CTD), we identify several residues in alpha-CTD that are important
      for CysB-dependent transcription from the cysP promoter. After probing potential
      protein-protein contacts in vivo with a LexA-based two-hybrid system, we propose
      that the '273 determinant' on alpha-CTD, including residues K271 and E273,
      represents a target for interaction with CysB at the cysP promoter.

PMID- 15255894
TI  - Neisseria meningitidis accelerates ferritin degradation in host epithelial cells
      to yield an essential iron source.
AB  - In order to colonize humans and cause disease, pathogenic bacteria must
      assimilate iron from their host. The vast majority of non-haem iron in humans is
      localized intracellularly, within the storage molecule ferritin. Despite the vast
      reserves of iron within ferritin, no pathogen has been demonstrated previously to
      exploit this molecule as an iron source. Here, we show that the Gram-negative
      diplococcus Neisseria meningitidis can trigger rapid redistribution and
      degradation of cytosolic ferritin within infected epithelial cells. Indirect
      immunofluorescence microscopy revealed that cytosolic ferritin is aggregated and
      recruited to intracellular meningococci (MC). The half-life of ferritin within
      cultured epithelial cells was found to decrease from 20.1 to 5.3 h upon infection
      with MC. Supplementation of infected epithelial cells with ascorbic acid
      abolished ferritin redistribution and degradation and prevented intracellular MC
      from replicating. The lysosomal protease inhibitor leupeptin slowed ferritin
      turnover and also retarded MC replication. Our laboratory has shown recently that
      MC can interfere with transferrin uptake by infected cells (Bonnah R.A., et al.,
      2000, Cell Microbiol 2: 207-218) and that, perhaps as a result, the infected
      cells have a transcriptional profile indicative of iron starvation (Bonnah, R.A.,
      et al., 2004, Cell Microbiol 6: 473-484). In view of these findings, we suggest
      that accelerated ferritin degradation occurs as a response to an iron starvation
      state induced by MC infection and that ferritin degradation provides
      intracellular MC with a critical source of iron.

PMID- 15255895
TI  - Translation repression by an RNA polymerase elongation complex.
AB  - Bacteriophage lambda N and bacterial Nus proteins together with a unique site NUT
      in the leader of the early viral N gene transcript bind RNA polymerase (RNAP) and
      form a highly processive antitermination complex; N bound at NUT also represses N
      translation. In this study, we investigate whether N and NUT cause N translation
      repression as part of the antitermination complex by testing conditions that
      inhibit the formation of the N-modified transcription complex for their effect on
      N-mediated translation repression. We show that nus and nut mutations that in
      combination destabilize multiple interactions in the antitermination complex
      prevent N-mediated translation repression. Likewise, transcription of the nut-N
      region by T7 RNAP, which does not lead to the assembly of an effective
      antitermination complex when N is supplied, eliminates translation repression. We
      also demonstrate that a unique mutant beta subunit of RNAP reduces N-mediated
      translation repression, and that overexpression of transcription factor NusA
      suppresses this defect. We conclude that the N-modified RNAP transcription
      complex is necessary to repress N translation.

PMID- 15255896
TI  - Dimer-induced signal propagation in Spo0A.
AB  - Spo0A, the response regulator protein controlling the initiation of sporulation
      in Bacillus, has two distinct domains, an N-terminal phosphoacceptor (or
      receiver) domain and a C-terminal DNA-binding (or effector) domain. The
      phosphoacceptor domain mediates dimerization of Spo0A on phosphorylation. A
      comparison of the crystal structures of phosphorylated and unphosphorylated
      response regulators suggests a mechanism of activation in which structural
      changes originating at the phosphorylatable aspartate extend to the
      alpha4beta5alpha5 surface of the protein. In particular, the data show an
      important role in downstream signalling for a conserved aromatic residue (Phe-105
      in Spo0A), the conformation of which alters upon phosphorylation. In this study,
      we have prepared a Phe-105 to Ala mutant to probe the contribution of this
      residue to Spo0A function. We have also made an alanine substitution of the
      neighbouring residue Tyr-104 that is absolutely conserved in the Spo0As of spore
      forming Bacilli. The spo0A(Y104A) and spo0A(F105A) alleles severely impair
      sporulation in vivo. In vitro phosphorylation of the purified proteins by
      phosphoramidate is unaffected, but dimerization and DNA binding are abolished by
      the mutations. We have identified intragenic suppressor mutations of spo0A(F105A)
      and shown that these second-site mutations in the purified proteins restore
      phosphorylation-dependent dimer formation. Our data support a model in which
      dimerization and signal transduction between the two domains of Spo0A are
      mediated principally by the alpha4beta5alpha5 signalling surface in the receiver
      domain.

PMID- 15255897
TI  - Investigating the role of secA2 in secretion and glycosylation of a fimbrial
      adhesin in Streptococcus parasanguis FW213.
AB  - Adhesion of Streptococcus parasanguis FW213, a primary colonizer, to the tooth
      surface is mediated mainly by peritrichous long fimbriae. The fimbrial structural
      unit, Fap1, is indispensable for fimbriae biogenesis, adhesion to an in vitro
      tooth model and biofilm formation. Mature Fap1 is a glycoprotein with an apparent
      molecular mass of 200 kDa. Glycosylated Fap1 is not present in some mutants
      screened from a transposon mutant library. Localization of the transposition
      sites revealed a gene determined to be secA2, which is distinct from the
      canonical secA gene. In FW213, glycosylated Fap1 was present in all the
      subcellular fractions including the cytoplasm. In VT1574, a non-polar mutant of
      secA2 generated by in frame deletion, Fap1 was not secreted. Glycosylated Fap1
      was present in the membrane and cytoplasm of the mutant, although in greatly
      reduced amounts. Fap1 secretion and abundance were restored when VT1574 was
      complemented by a plasmid-borne secA2. The secretion defect of the secA2 mutation
      appears to be limited to a small group of proteins such as Fap1 and FimA. These
      data suggested that Fap1 secretion rather than glycosylation was the major effect
      of the deletion of secA2; however, this deletion also had an impact on Fap1
      abundance. Two more secA2 mutants with different regions deleted were tested for
      their ability to secrete Fap1. One mutant was completely unable to secrete Fap1
      while the other was able to secrete, but in a decreased amount. These data
      suggest that the region deleted in the latter mutant (nucleotides 2032-2337) is
      dispensable for Fap1 secretion.

PMID- 15255898
TI  - Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation.
AB  - While studying virulence gene regulation in Vibrio cholerae during infection of
      the host small intestine, we identified VieA as a two-component response
      regulator that contributes to activating expression of cholera toxin. Here we
      report that VieA represses transcription of Vibrio exopolysaccharide synthesis
      (vps) genes involved in biofilm formation by a mechanism independent of its
      phosphorelay and DNA-binding activities. VieA controls the intracellular
      concentration of the cyclic nucleotide second messenger cyclic diguanylate (c-di
      GMP) using an EAL domain that functions as a c-di-GMP phosphodiesterase. Two
      dimensional thin layer chromatography of nucleotide extracts confirmed that VieA
      reduces the concentration of c-di-GMP, opposing the action of c-di-GMP synthetase
      proteins. Expression of unrelated V. cholerae c-di-GMP synthetase or
      phosphodiesterae proteins also modulated c-di-GMP concentration and vps gene
      expression. We propose that c-di-GMP synthetase and phosphodiesterase domain
      containing proteins contribute to regulating biofilm formation by controlling c
      di-GMP concentration.

PMID- 15255899
TI  - RovA is autoregulated and antagonizes H-NS-mediated silencing of invasin and rovA
      expression in Yersinia pseudotuberculosis.
AB  - The transcriptional activator RovA of Yersinia pseudotuberculosis, a member of
      the SlyA/Hor family, activates its own expression and that of the virulence
      factor invasin in response to moderate growth temperature, but not at 37 degrees
      C. In this work, we analysed the mechanism of RovA-dependent transcription of the
      rovA and inv genes. We found that rovA is transcribed by two different promoters.
      Sequences located upstream and downstream of the promoters were involved in rovA
      autoregulation and interacted specifically with the RovA protein. To define the
      nucleotides recognized by the RovA protein, we determined the RovA binding sites
      in the rovA and the inv regulatory region and revealed related AT-rich sequence
      motifs at diverse positions relative to the transcriptional start sites. We also
      showed that rovA and the RovA-dependent inv gene were both subject to silencing
      by the nucleoid-associated H-NS protein of Y. pseudotuberculosis. The binding
      sites of the H-NS and RovA proteins in the rovA and inv regulatory sequences were
      superimposed, and the presence of the RovA protein alleviated H-NS-mediated
      repression of the rovA and inv promoter. Moreover, loss of H-NS function led to a
      significant increase in rovA and inv transcription nearly independently of RovA,
      indicating that RovA acts mainly as an antirepressor. We therefore hypothesize
      that the transcription level of RovA-dependent genes reflects the outcome of the
      RovA/H-NS competition and the rovA autoregulatory mechanism.

PMID- 15255900
TI  - Molecular analysis of the psa permease complex of Streptococcus pneumoniae.
AB  - The psaBCA locus of Streptococcus pneumoniae encodes a putative ABC Mn2+-permease
      complex. Downstream of the operon is psaD, which may be co-transcribed and
      encodes a thiol peroxidase. Previously, there has been discordance concerning the
      phenotypic impact of mutations in the psa locus, resolution of which has been
      complicated by differences in mutant construction and the possibility of polar
      effects. Here, we constructed unmarked, in frame deletion mutants DeltapsaB,
      DeltapsaC, DeltapsaA, DeltapsaD, DeltapsaBC, DeltapsaBCA and DeltapsaBCAD in S.
      pneumoniae D39 to examine the role of each gene within the locus in Mn2+ uptake,
      susceptibility to oxidative stress, virulence, nasopharyngeal colonization and
      chain morphology. The requirement for Mn2+ for growth and transformation was also
      investigated for all mutants. Inductively coupled plasma mass spectrometry (ICP
      MS) analysis provided the first direct evidence that PsaBCA is indeed a Mn2+
      transporter. However, this study did not substantiate previous reports that the
      locus plays a role in choline-binding protein pro-duction or chain morphology. We
      also confirmed the importance of the Psa permease in systemic virulence and
      resistance to superoxide and hydrogen peroxide, as well as demonstrating a role
      in nasopharyngeal colonization for the first time. Further evi-dence is provided
      to support the requirement for Mn2+ supplementation for growth and transformation
      of DeltapsaB, DeltapsaC, DeltapsaA, DeltapsaBC, DeltapsaBCA and DeltapsaBCAD
      mutants. However, transformation, as well as growth, of the DeltapsaD mutant was
      not dependent upon Mn2+ supplementation. We also show that, apart from
      sensitivity to hydrogen peroxide, the DeltapsaD mutant exhibited essentially
      similar phenotypes to those of the wild type. Western blot analysis with a PsaD
      antiserum showed that deleting any of the genes upstream of psaD did not affect
      its expression. However, we found that deleting psaB resulted in decreased
      expression of PsaA relative to that in D39, whereas deleting both psaB and psaC
      resulted in at least wild-type levels of PsaA.

PMID- 15255901
TI  - Tailoring modification of deoxysugars during biosynthesis of the antitumour drug
      chromomycin A by Streptomyces griseus ssp. griseus.
AB  - Chromomycin A3 is a member of the aureolic acid group family of antitumour drugs.
      Three tailoring modification steps occur during its biosynthesis affecting the
      sugar moieties: two O-acetylations and one O-methylation. The 4-O-methylation in
      the 4-O-methyl-D-oliose moiety of the disaccharide chain is catalysed by the
      cmmMIII gene product. Inactivation of this gene generated a chromomycin-non
      producing mutant that accumulated three unmethylated derivatives containing all
      sugars but differing in the acylation pattern. Two of these compounds were shown
      to be substrates of the methyltransferase as determined by their bioconversion
      into chromomycin A2 and A3 after feeding these compounds to a Streptomyces albus
      strain expressing the cmmMIII gene. The same single membrane-bound enzyme,
      encoded by the cmmA gene, is responsible for both acetyl transfer reactions,
      which convert a relatively inactive compound into the bioactive chromomycin A3.
      Insertional inactivation of this gene resulted in a mutant accumulating a
      dideacetylated chromomycin A3 derivative. This compound, lacking both acetyl
      groups, was converted in a two-step reaction via the 4E-monoacetylated
      intermediate into chromomycin A3 when fed to cultures of S. albus expressing the
      cmmA gene. This acetylation step would occur as the last step in chromomycin
      biosynthesis, being a very important event for self-protection of the producing
      organism. It would convert a molecule with low biological activity into an active
      one, in a reaction catalysed by an enzyme that is predicted to be located in the
      cell membrane.

PMID- 15255902
TI  - Analysis in vitro and in vivo of the transcriptional regulator CrgA of Neisseria
      meningitidis upon contact with target cells.
AB  - Contact between CrgA, a LysR-like regulatory protein in Neisseria meningitidis,
      and DNA is involved in the repression of several bacterial genes upon contact
      with epithelial cells. We used a defined in vitro system containing crgA
      promoter, purified RNA polymerase (RNAP) and purified CrgA protein to demonstrate
      that CrgA was directly responsible for this transcriptional repression.
      Interaction between the C-terminal domain of CrgA and the RNAP led to the
      production of short abortive transcripts, suggesting that CrgA may act by
      preventing RNAP from clearing the promoter. We probed the regulation by CrgA of
      its own production by analysing CrgA-DNA contacts during cell-bacteria
      interaction by assaying in vivo protection against dimethyl sulphate (DMS)
      methylation. Comparison of DMS footprints in vitro and in vivo suggested that
      CrgA repressed transcription through specific base contacts, probably in the
      major groove of the DNA double helix, resulting in DNA looping. Upon contact with
      target cells, CrgA was released from the DNA, allowing transcription of the
      target gene to proceed to elongation and facilitating tight control of the
      expression of genes regulated by CrgA.

PMID- 15255903
TI  - A role for creD, a carbon catabolite repression gene from Aspergillus nidulans,
      in ubiquitination.
AB  - In Aspergillus nidulans, it is known that creB encodes a deubiquitinating enzyme
      that forms a complex with the WD40 motif containing protein encoded by creC, that
      mutations in these genes lead to altered carbon source utilization and that the
      creD34 mutation suppresses the phenotypic effects of mutations in creC and creB.
      Therefore, creD was characterized in order to dissect the regulatory network that
      involves the CreB-CreC deubiquitination complex. CreD contains arrestin domains
      and PY motifs and is highly similar to the Rod1p and Rog3p proteins from
      Saccharomyces cerevisiae. An additional gene was identified in the A. nidulans
      genome that also encodes an arrestin and PY motif-containing protein, which we
      have designated apyA, and thus two similar proteins also exist in A. nidulans. In
      S. cerevisiae, Rod1p and Rog3p interact with the ubiquitin ligase Rsp5p, and so
      the A. nidulans homologue of Rsp5p was identified, and the gene encoding this
      HECT ubiquitin ligase was designated hulA. CreD and ApyA were tested for protein
      protein interactions with HulA via the bacterial two-hybrid system, and ApyA
      showed strong interaction, and CreD showed weak interaction, with HulA in this
      system.

PMID- 15255904
TI  - Membrane localization itself but not binding to IICB is directly responsible for
      the inactivation of the global repressor Mlc in Escherichia coli.
AB  - Mlc is a global transcriptional repressor involved in the regulation of genes
      linked to glucose metabolism. The activity of Mlc is modulated through the
      interaction with a major glucose transporter, IICBGlc, in response to external
      glucose. To understand how IICBGlc-Mlc interaction controls the repressor
      activity of Mlc, we attempted to isolate Mlc mutants that retain the ability to
      repress target genes even in the presence of glucose. The Mlc mutants were tested
      for their ability to interact with IICBGlc. Mutants in which a single amino acid
      substitution occurs in the N-terminal portion were no longer able to bind to
      IICBGlc, suggesting that the N-terminal region of Mlc is primarily responsible
      for the interaction with IICBGlc. To examine whether the Mlc-IICBGlc interaction
      and/or the membrane localization of Mlc per se are essential for the inactivation
      of Mlc, the properties of several hybrid proteins in which either IIBGlc or Mlc
      is fused to membrane proteins were analysed. The cytoplasmic IIBGlc domain failed
      to inhibit the Mlc action although it retains the ability to bind Mlc in cells.
      However, it gained the ability to inhibit the Mlc activity when it was fused to a
      membrane protein LacY. In addition, we showed that Mlc is inactivated when fused
      to membrane proteins but not when fused to cytoplasmic proteins. We conclude that
      the IICBGlc-Mlc interaction is dispensable for the inactivation of Mlc, and that
      membrane localization is directly responsible for the inactivation of Mlc.

PMID- 15255905
TI  - The bromodomain-containing protein Bdf1p acts as a phenotypic and transcriptional
      multicopy suppressor of YAF9 deletion in yeast.
AB  - It was observed previously that the deletion of the open reading frame YNL107w
      (YAF9) was highly pleiotropic in yeast and caused defective growth phenotypes in
      the presence of several unrelated inhibitors, including caesium chloride. We have
      selected multicopy extragenic suppressor genes, revealing that this phenotype can
      be suppressed by overdosing the transcription factors BDF1 and GAT1 in the
      yaf9Delta strain. We focused our analysis on suppression by BDF1 and performed a
      genome-wide transcript analysis on a yaf9Delta strain, compared with the wild
      type and BDF1-suppressed strains. YAF9 deletion has a clear effect on
      transcription and leads to modulation of the level of expression of several
      genes. Transcription of a considerable portion of the underexpressed genes is
      restored to wild-type levels in the BDF1-suppressed strain. We show by chromatin
      immunoprecipitation that both Yaf9p and Bdf1p bind to promoters of some of these
      genes and that the level of H3 and H4 acetylation at one of these promoters is
      significantly lowered in the yaf9 deleted strain, compared with the wild-type and
      the BDF1-suppressed strains.

PMID- 15255906
TI  - The Candida albicans CaACE2 gene affects morphogenesis, adherence and virulence.
AB  - Morphogenesis between yeast and hyphal growth is a characteristic associated with
      virulence in Candida albicans and involves changes in the cell wall. In
      Saccharomyces cerevisiae, the transcription factor pair Ace2p and Swi5p are key
      regulators of cell wall metabolism. Here, we have characterized the CaACE2 gene,
      which encodes the only C. albicans homologue of S. cerevisiae ACE2 and SWI5.
      Deleting CaACE2 results in a defect in cell separation, increased invasion of
      solid agar medium and inappropriate pseudohyphal growth, even in the absence of
      external inducers. The mutant cells have reduced adherence to plastic surfaces
      and generate biofilms with distinctly different morphology from wild-type cells.
      They are also avirulent in a mouse model. Deleting CaACE2 has no effect on
      expression of the chitinase gene CHT2, but expression of CHT3 and the putative
      cell wall genes CaDSE1 and CaSCW11 is reduced in both yeast and hyphal forms. The
      CaAce2 protein is localized to the daughter nucleus of large budded cells at the
      end of mitosis. C. albicans Ace2p therefore plays a major role in morphogenesis
      and adherence and resembles S. cerevisiae Ace2p in function.

PMID- 15255907
TI  - Transcription of the sporulation gene ssgA is activated by the IclR-type
      regulator SsgR in a whi-independent manner in Streptomyces coelicolor A3(2).
AB  - SsgA plays an important role in the control of sporulation-specific cell division
      and morphogenesis of streptomycetes, and ssgA null mutants have a rare
      conditionally non-sporulating phenotype. In this paper we show that transcription
      of ssgA and of the upstream-located ssgR, an iclR-type regulatory gene, is
      developmentally regulated in Streptomyces coelicolor and activated towards the
      onset of sporulation. A constructed ssgR null mutant was phenotypically very
      similar to the ssgA mutant. The absence of ssgA transcription in this mutant is
      probably the sole cause of its sporulation deficiency, as wild-type levels of
      sporulation could be restored by the SsgR-independent expression of ssgA from the
      ermE promoter. Binding of a truncated version of SsgR to the ssgA promoter region
      showed that ssgA transcription is directly activated by SsgR; such a dependence
      of ssgA on SsgR in S. coelicolor is in clear contrast to the situation in S.
      griseus, where ssgA transcription is activated by A-factor, and its control by
      the SsgR orthologue, SsfR, is far less important. Our failure to complement the
      ssgR mutant with S. griseus ssfR suggests functional differences between the
      genes. These observations may explain some of the major differences in
      developmental control between the phylogenetically divergent species S.
      coelicolor and S. griseus, highlighted in a recent microreview (Chater and
      Horinouchi (2003) Mol Microbiol 48: 9-15). Surprisingly, transcription of ssgA
      and ssgR is not dependent on the early whi genes (whiA, whiB, whiG, whiH, whiI
      and whiJ ).

PMID- 15255910
TI  - Nurses' ethical perceptions about coercion.
AB  - PURPOSE OF THE STUDY: The purpose of this study was to describe Finnish
      psychiatric nurses' ethical perceptions about coercive measures in acute
      psychiatric setting. METHODS: The data were collected with a questionnaire
      developed for this study. The sample included 170 Finnish psychiatric nurses on
      acute wards in five psychiatric hospitals. The data were analysed using frequency
      and percentage distributions, mean and standard deviations. The internal
      consistency of the instrument was explored with Cronbach's alpha. The association
      between the background variables and the sum score of the items of the
      questionnaire was tested with Mann-Whitney U-test and Kruskal-Wallis test. The
      open-ended question was analysed with content analysis. RESULTS: Some psychiatric
      nurses perceived coercive measures as ethically problematic. In particular, the
      implementation of forced medication (18%), four-point restraints (16%) and
      patient seclusion (11%) were perceived as ethically problematic. Female nurses
      and nurses who worked on closed wards perceived the measures to be more
      problematic than male nurses and nurses who did not work on closed wards.
      CONCLUSION: In Finland, special attention has been paid to ethical questions
      related to the care of psychiatric patients and to the enhancement of patients'
      rights, yet the majority of the nurses participating in the survey did not
      perceive coercive measures as ethically problematic. More research on this issue
      as well as further education of the personnel and more extensive teaching of
      ethics in nursing schools are needed to support the ability of the psychiatric
      personnel to identify ethically problematic situations. In addition, it is
      important to consider new measures for generating genuine moral reflection among
      the personnel on the usage of coercive measures as well as on their effectiveness
      and legitimacy in the psychiatric care.

PMID- 15255911
TI  - The effect of psychological and educational counselling in reducing anxiety in
      nursing students.
AB  - A quasi-experimental pre-, post-test, follow-up and control group design was used
      to investigate the effect of psychological and educational counselling in
      reducing anxiety in nursing students. The research study used methodological
      triangulation, involving the use of structured data collection techniques such as
      standardized questionnaires and semi-structured focus groups. Focus groups were
      used to provide greater insight regarding the student's opinions. The sample
      consisted of 100 second- and fourth-year baccalaureate nursing students from the
      Faculty of Nursing at Shiraz University of Medical Sciences, Iran. They were
      randomly assigned to either an experimental group (n = 50) or a control group (n
      = 50). The experimental group received a 12-week intervention programme.
      Quantitative analysis of data was undertaken using t-test and analysis of
      variance for repeated measures to test differences between and within groups. The
      results indicated that from pre- to post-test there was no statistically
      significant reduction in anxiety between groups, but there was a statistically
      significant reduction in anxiety after one semester (in the follow-up). Student
      self-esteem was increased significantly from pre- to post-test. This increase was
      statistically significant and remained the same in follow-up. A statistically
      significant difference was seen in the student grade point average from pre-test
      to follow-up in the experimental group but not for the control group. The
      implementation of an intervention programme reduced their anxiety, increased
      their self-esteem and improved their grade point average over time.

PMID- 15255912
TI  - The Nurses' Global Assessment of Suicide Risk (NGASR): developing a tool for
      clinical practice.
AB  - Contemporary and established literature indicates that people with mental health
      problems are at a higher risk of suicide than the general population. Because
      suicide is a multifaceted, complex phenomenon, risk assessment within the mental
      health care system requires a pluralistic, multidimensional and multiprofessional
      response. While assessment tools may provide useful guidance, especially guarding
      against complacency and over confidence, the fundamental basis of risk assessment
      must involve a thorough examination of the personal, interpersonal and social
      circumstances of each individual. Such thorough and rigorous assessments, the
      authors of this paper would add, require a degree of 'clinical judgement'. As a
      rule, inexperienced members of mental health care staff should not be charged
      with the responsibility of conducting suicide risk assessments without sound
      mentorship. However, with the right support and assessment tool, the novice
      practitioner might develop the kind of clinical judgement necessary for this
      critical task. Accordingly, this paper traces the development of the Nurses'
      Global Assessment of Suicide Risk (NGASR). It illustrates the practice
      development context out of which the need for the tool arose; it outlines the key
      evidence that underpins the construction of the tool and it is described. It is
      important to point out that as yet, no wide scale, quantitative validation of the
      tool has been conducted. Therefore, at this point, the tool should be treated
      with a degree of appropriate caution. Nevertheless, the preliminary attempts that
      have been made to 'validate' or 'rate' the tool in practice are included. While
      acknowledging that any risk assessment tool represents only one aspect of the
      necessarily broader assessment of risk, the NGASR appears to provide a useful
      template for the nursing assessment of suicide risk, especially for the novice.

PMID- 15255913
TI  - Short shrift for the sane? The hospital management of self-harm patients with and
      without mental illness.
AB  - In recent years the British government has sought to target service provision
      both on people with severe enduring mental illness and on those considered to be
      at risk of suicide. The study reported here suggests these policies may have had
      unforeseen repercussions on services for people who self-harm but have no
      identifiable mental illness. This paper compares the hospital management of self
      harm patients with and without mental illness. Over the years 1996-2000, a total
      of 4,329 self-harm patient attendances were recorded at the accident and
      emergency department of a British hospital. Whilst patients in 63.7% of
      attendances could reasonably have been considered to have some form of mental
      illness, we found that in the remaining 36.3% of attendances (where patients had
      no indicator of mental illness) a particularly poor standard of service was
      given. We suggest that if government targets for a reduction in the suicide rate
      are to be met, it is crucial that there should be marked improvements in services
      for all self-harm patients presenting at accident and emergency departments.
      However, in improving services we must be vigilant to the danger that targeting
      those with a mental illness may mean we fail to provide even basic levels of care
      for others.

PMID- 15255914
TI  - An investigation into how community mental health nurses assess the risk of
      violence from their clients.
AB  - Part of the community mental health nurse's (CMHN) role is the assessment of
      violence posed by clients. It explores factors such as the reduction of inpatient
      beds and the predictability of violent acts towards nursing staff. This study
      outlines how the risk of violence is assessed by generic CMHNs, by examining
      their awareness, understanding and perceptions of violence posed by their
      clients. The data were collected in one Trust, using questionnaire and focus
      groups. The findings emphasize the importance of historical evidence but also
      raise the issue of gut feelings of the nurse. They further identify that clinical
      judgement can be accurate in assessing for violence, and CMHNs relied upon
      experience and personal impressions of the presenting evidence, rather than
      through the use of a standardized instrument.

PMID- 15255915
TI  - Evaluating the introduction of a pilot client attachment scheme in mental health
      nursing education.
AB  - Client attachment (CA) allows student nurses to gain clinical experience through
      forming therapeutic attachments with individual clients, rather than through a
      series of location-based placements. This paper describes a pilot project that
      evaluated CA with pre-registration student mental health nurses. Using semi
      structured interviews, the researchers identified the students', their
      supervisor's, and their clients' experiences of CA. Most participants agreed that
      students were able to learn relevant and appropriate clinical skills, and to
      consolidate experience-increasing motivation, autonomy, organizational skills,
      and confidence.

PMID- 15255916
TI  - Predicting inpatient violence in acute psychiatric wards using the Broset
      Violence-Checklist: a multicentre prospective cohort study.
AB  - The Norwegian Broset-Violence-Checklist (BVC) is one of the few instruments that
      is suitable for short-term prediction of violence of psychiatric inpatients by
      nursing staff in routine care. The instrument assesses the presence or absence of
      six behaviours or states frequently observed before a violent incident. We
      conducted a study to elucidate whether the predictive properties of the BVC are
      retained in other psychiatric settings than the original north-Norwegian
      validation dataset. During their admission period, 219 consecutive patients
      admitted to six acute psychiatric wards were assessed as to the risk for attack
      using a German version of the BVC (BVC-G). Data on preventive measures were
      concurrently collected. Aggressive incidents were registered using an instrument
      equivalent to the Staff Observation of Aggression Scale (SOAS-R). Fourteen
      attacks towards staff were observed with incident severity ranging from 5 to 18
      of a possible 22 points. BVC-G sensitivity was 64.3%, the specificity 93.9%, the
      positive predictive value 11.1%, and the area under the receiver operating
      characteristic curve 0.88. In some false positive cases intense preventive
      measures had been implemented. The predictive accuracy of the BVC-G proved
      consistent with the Norwegian original.

PMID- 15255917
TI  - Ignoring the evidence dictating the practice: sexual orientation, suicidality and
      the dichotomy of the mental health nurse.
AB  - International epidemiological studies demonstrate that gay and bisexual males are
      four times more likely to report a serious suicide attempt than their
      heterosexual counterparts. Data on completed suicides, usually derived from
      mortality statistics misrepresent the rate of suicides among homosexual
      populations. However, an increasing number of studies comparing representative
      samples of gay, lesbian and bisexual youths with heterosexual controls
      demonstrate increased rates of mental health problems and subsequent suicide
      among the homosexual population. Homosexual orientation must therefore be
      considered a risk factor for mental distress and as such should be a focus for
      any contemporary public health agenda. One of the difficulties of addressing the
      problem through a public health agenda is the juxtaposition proffered by our
      political and social environment. The Diagnostic and Statistical Manual of Mental
      Disorder ceased to define homosexuality as pathological in 1973 replacing it with
      a new 'illness' of 'gender identity disorder'. Until recently in England, Section
      28 of the Local Government Act (1988), forbidding the promotion of homosexuality,
      further reinforced negativity towards this group of people. This compounded the
      negative mental health consequences for those developing a gay sexual orientation
      in a climate of heterosexism. Current health care policy in England concerns
      itself with the rising number of suicides among young people but fails to
      acknowledge the importance of the research findings relating to gay people by
      integrating them into the development of mental health policy. This paper reviews
      the literature relating to homosexual people and suicidality, and addresses the
      seriousness of a policy rhetoric which results from ignoring the evidence while
      dictating mental health nursing practice.

PMID- 15255918
TI  - 'Therapy as well as the tablets': an exploratory study of service users' views of
      community mental health nurses' (CMHNs) responses to hearing voices.
AB  - Mental health nurses have traditionally been discouraged from engaging with
      service users' experiences of hearing voices and to reinforce reality. However,
      this may not be a helpful way of intervening in what can be a very distressing
      symptom. There is little evidence of service users' experiences of community
      mental health nurses' (CMHNs) responses to their voices. This paper presents the
      findings of an exploratory interview study of a sample (n = 20) of service users
      to ascertain their perception of CMHN responses to their experience of hearing
      voices. Data are both quantitative and qualitative in nature. Content analysis of
      the qualitative elements of the study suggests responses can be conceptualized as
      facilitators, barriers and attributions. CMHNs are considered to be allies and
      the quality of the relationship is deemed important. The therapeutic repertoire
      of CMHNs, however, is seen as limited and rarely extends beyond facilitating
      access to the psychiatrist for review of medication.

PMID- 15255919
TI  - Smoking and mental health nurses: a survey of clinical staff in a psychiatric
      hospital.
AB  - There is a lack of evidence on the prevalence of smoking among mental health
      nurses, and the beliefs and attitudes they hold about smoking at work. This paper
      describes results from a cross-sectional survey of clinical staff working in a UK
      specialist charitable-status psychiatric hospital and focuses on the responses of
      registered mental health nurses. Questionnaires specifically developed for this
      study were sent to all 1371 clinical employees. Completed questionnaires were
      returned by 167 of 429 (38.9%) registered nurses (RNs), 300 of 842 (35.6%)
      nursing assistants (NAs), and 123 of 200 (61.5%) other health professionals
      (OHPs). Twenty-nine (17.4%) RNs, 93 (31%) NAs and eight (6.5%) OHPs reported
      themselves as current smokers. Differences in response to attitudinal questions
      between groups could not be attributed to age. RN smokers were significantly more
      likely than RN non-smokers to state that staff should be allowed to smoke with
      patients, and to report therapeutic value for patients in this activity. RN
      smokers were less likely than RN non-smokers to report that patients should be
      encouraged to stop smoking. RNs were significantly more likely than OHPs to
      report therapeutic value for patients in smoking with staff, even after
      controlling for the possible confounding effect of smoking status. Implications
      of the survey are discussed in the context of the international literature,
      including the disproportionately high smoking prevalence among patients living in
      psychiatric institutions and current guidelines to move towards no 'smoking
      allowed' areas for staff working in them.

PMID- 15255920
TI  - Assertive outreach nurses' experience of engagement.
AB  - There are currently no studies available in the literature to highlight nurses'
      experiences of the assertive outreach (AO) engagement process. This study aimed
      to understand how AO nurses experience this process and what can be learned from
      it. The participants were five nurses working in a rural AO service in one
      county. Methodological considerations were rooted in the work of Martin Heidegger
      and the data analysed using the hermeneutic phenomenological thematic method. The
      data-gathering tool was semi-structured interviews. Seven major themes emerged to
      construct the nurses' understanding of their experience of assertive engagement.
      These were: (1) having time; (2) anticipatory persistence and tired dejection;
      (3) pressure, relief and satisfaction; (4) being the human professional
      confluence; (5) accepting anxiety and fear; (6) working and learning together;
      and (7) bringing the caring attitude. This paper focuses on the seven emerging
      themes and discusses the implications and recommendations for nurses practising
      in the AO setting.

PMID- 15255921
TI  - The development and evaluation of a telepsychiatry service for prisoners.
AB  - The introduction of increasingly sophisticated telecommunication systems seems to
      offer opportunities to respond to some of the key problems around structural and
      spatial inequalities in access to health care. There is evidence which suggests
      that serious mental health problems are common among prisoners and psychiatric
      comorbidity is the norm. Many prisoners have complex mental health needs, but
      more often than not these remain unaddressed. Telepsychiatry is one strategy to
      improve the accessibility and quality of mental health care in the prison
      setting. This paper firstly reviews the current prison health care system and
      then describes a research study which is focused on the development and
      evaluation of a telepsychiatry service for prisoners. This study has investigated
      what is lost or gained in a psychiatric assessment when it is conducted via
      telepsychiatry. The researcher compared the inter-rater reliability between two
      raters interviewing 80 participants in an observer/interviewer split
      configuration in telepsychiatry and same room settings. The measure used was the
      Comprehensive Psychopathology Rating Scale. Prisoners and prison staff also took
      part in semi-structured interviews which focused on their satisfaction and
      acceptability of the telepsychiatry service. A cost comparison of the
      telepsychiatry service with the existing visiting service was conducted. This
      paper outlines the study design and focuses on the potential impact that
      telepsychiatry may have upon the practice setting.

PMID- 15255922
TI  - A staff perspective of early warning signs intervention for individuals with
      psychosis: clinical and service implications.
AB  - Research has established the benefits of early warnings signs monitoring in the
      prevention of relapse for individuals with psychosis. This study explored staff
      views (n = 8) of the implementation of an early warning signs clinic within a day
      hospital of an adult mental health service. A qualitative methodology using focus
      groups was adopted and content analysis was used to discover themes arising from
      the data. Overall, the data indicated a positive view of the early warning signs
      clinic, with benefits for clients, staff and their relationship; and for service
      delivery and resources. The clinical and service implications are discussed.

PMID- 15255923
TI  - Exercise: a neglected intervention in mental health care?
AB  - This paper reports the results of a literature review examining the effects of
      exercise on mental health and well-being. Throughout history many societies,
      ancient and modern, have used exercise as a means of preventing disease, and
      promoting health and well-being. There is evidence that exercise is beneficial
      for mental health; it reduces anxiety, depression, and negative mood, and
      improves self-esteem and cognitive functioning. Exercise is also associated with
      improvements in the quality of life of those living with schizophrenia. However,
      exercise is seldom recognized by mainstream mental health services as an
      effective intervention in the care and treatment of mental health problems. There
      is evidence to suggest that exercise may be a neglected intervention in mental
      health care.

PMID- 15255924
TI  - A concept analysis of forensic risk.
AB  - Forensic risk is a term used in relation to many forms of clinical practice, such
      as assessment, intervention and management. Rarely is the term defined in the
      literature and as a concept it is multifaceted. Concept analysis is a method for
      exploring and evaluating the meaning of words. It gives precise definitions, both
      theoretical and operational, for use in theory, clinical practice and research. A
      concept analysis provides a logical basis for defining terms through providing
      defining attributes, case examples (model, contrary, borderline, related),
      antecedents and consequences and the implications for nursing. Concept analysis
      helps us to refine and define a concept that derives from practice, research or
      theory. This paper will use the strategy of concept analysis to find a working
      definition for the concept of forensic risk. In conclusion, the historical
      background and literature are reviewed using concept analysis to bring the term
      into focus and to define it more clearly. Forensic risk is found to derive both
      from forensic practice and from risk theory. A proposed definition of forensic
      risk is given.

PMID- 15255925
TI  - Motivational interviewing: a hammer looking for a nail?

PMID- 15255926
TI  - A consideration of the social trajectory of psychiatric nursing in Ireland.

PMID- 15255929
TI  - The tyrosine kinase inhibitor AG126 restores receptor signaling and blocks
      release functions in activated microglia (brain macrophages) by preventing a
      chronic rise in the intracellular calcium level.
AB  - We recently reported that lasting activation of mouse microglial cells with
      bacterial lipopolysaccharide (LPS) chronically elevated the basal intracellular
      calcium concentration ([Ca2+]i). This correlated to an attenuated calcium
      signaling of complement (C5a) and purinergic (UTP) receptors as well as to the
      capacity for effective production of cytokines-chemokines. Here, we demonstrate
      that these adjustments in the [Ca2+]i regulation require a critical protein
      tyrosine kinase (PTK) function--even in varying stimulation scenarios. Changes in
      basal [Ca2+]i and calcium signaling are not restricted to Gram-negative bacterial
      confrontation. Pneumococcal cell wall (PCW) modelling Gram-positive infection
      causes virtually the same effects. Moreover, decreases in calcium signaling
      efficacy are neither associated with altered receptor expression, nor mediated by
      autocrine loops. Administration of microglial release products, transfer of
      conditioned supernatant or presence of a radical scavenger during LPS or PCW
      treatments have no consequence. However, both the elevation in basal [Ca2+]i as
      well as the suppression of C5a- and UTP-evoked calcium signals are selectively
      and dose-dependently reversed by tyrphostin AG126, a PTK inhibitor that,
      moreover, blocks inducible nitric oxide and cytokine-chemokine release. The
      findings suggest that the AG126-sensitive PTK critically controls both sensory
      and executive features of the microglial activation process via sustained up
      regulation of basal [Ca2+]i.

PMID- 15255930
TI  - Functional expression of rat ABCG2 on the luminal side of brain capillaries and
      its enhancement by astrocyte-derived soluble factor(s).
AB  - The purpose of the present study was to clarify the expression, transport
      properties and regulation of ATP-binding cassette G2 (ABCG2) transporter at the
      rat blood-brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned
      from rat brain capillary fraction. In rABCG2-transfected HEK293 cells, rABCG2 was
      detected as a glycoprotein complex bridged by disulfide bonds, possibly a
      homodimer. The protein transported mitoxantrone and BODIPY-prazosin. In rat brain
      capillary fraction, rABCG2 protein was also detected as a glycosylated and
      disulfide-linked complex. Immunohistochemical analysis revealed that rABCG2 was
      localized mainly on the luminal side of rat brain capillaries, suggesting that
      rABCG2 is involved in brain-to-blood efflux transport. For the regulation study,
      conditionally immortalized rat brain capillary endothelial (TR-BBB13), astrocyte
      (TR-AST4) and pericyte (TR-PCT1) cell lines were used as an in vitro BBB model.
      Following treatment of TR-BBB13 cells with conditioned medium of TR-AST4 cells,
      the Ko143 (an ABCG2-specific inhibitor)-sensitive transport activity and rABCG2
      mRNA level were significantly increased, whereas conditioned medium of TR-PCT1
      cells had no effect. These results suggest that rat brain capillaries express
      functional rABCG2 protein and that the transport activity of the protein is up
      regulated by astrocyte-derived soluble factor(s) concomitantly with the induction
      of rABCG2 mRNA.

PMID- 15255931
TI  - Oligomeric potential of the M2 muscarinic cholinergic receptor.
AB  - G protein-coupled receptors are known to exist as oligomers. Although such
      aggregates often are referred to as dimers, there is little direct evidence
      regarding their oligomeric size. In the present investigation, c-Myc-, FLAG-, and
      influenza hemagglutinin (HA)-tagged forms of the M2 muscarinic receptor have been
      coexpressed in Sf9 cells to probe for aggregates larger than a dimer.
      Immunochromatography, immunoprecipitation, and immunoblotting were carried out
      with various combinations of antibodies directed against the different epitopes
      to demonstrate that all three tagged forms of the receptor can be immunopurified
      within a single complex. Extracts of the M2 muscarinic receptor from Sf9 cells
      therefore contain aggregates that are at least trimeric, and the levels detected
      point to the existence of larger complexes. The data also suggest that the
      oligomers coexist with a sizeable population of monomers.

PMID- 15255932
TI  - Molecular characterization of neurohybrid cell death induced by Alzheimer's
      amyloid-beta peptides via p75NTR/PLAIDD.
AB  - One of the most important pathological features of Alzheimer's disease (AD) is
      extracellular senile plaques, whose major component is amyloid-beta peptides
      (Abeta). Abeta binds to the extracellular domain of p75NTR (p75 neurotrophin
      receptor) and induces neuronal cell death. We investigated the molecular
      mechanism of Abeta-induced neurotoxicity in detail from the standpoint of
      interaction between p75NTR and its recently identified relative, PLAIDD (p75-like
      apoptosis-inducing death domain). Using F11 neuronal hybrid cells, we demonstrate
      that there are two distinct pathways for Abeta-induced toxicity mediated by
      p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR,
      Go, JNK, NADPH oxidase and caspase3-related caspases. We found that PLAIDD and Gi
      proteins, heterotrimeric G proteins, are involved in the alternative Abeta
      induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by
      Abeta is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3
      related caspases. In addition, we found that HN, ADNF, IGF-I, or bFGF inhibits
      both pathways of Abeta-induced neurotoxicity mediated by p75NTR.

PMID- 15255933
TI  - In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat
      hypothalamus.
AB  - Melatonin is the pineal hormone that acts via a pertussis toxin-sensitive G
      protein to inhibit adenylate cyclase. However, the intracellular signalling
      effects of melatonin are not completely understood. Melatonin receptors are
      mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both
      humans and rats. The SCN directly controls, amongst other mechanisms, the
      circadian rhythm of plasma glucose concentration. In this study, using
      immunoprecipitation and immunoblotting, we show that melatonin induces rapid
      tyrosine phosphorylation and activation of the insulin receptor beta-subunit
      tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR
      activation, tyrosine phosphorylation of IRS-1 was detected. In addition,
      melatonin induced IRS-1/PI3-kinase and IRS-1/SHP-2 associations and downstream
      AKT serine phosphorylation and MAPK (mitogen-activated protein kinase)
      phosphorylation, respectively. These results not only indicate a new signal
      transduction pathway for melatonin, but also a potential cross-talk between
      melatonin and insulin.

PMID- 15255934
TI  - Inhibition of the E2F-1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid
      beta-peptide-induced apoptosis of PC12 cells.
AB  - Amyloid beta-peptide (Abeta)-induced cell death may involve activation of the E2F
      1 transcription factor and other cell cycle-related proteins. In previous
      studies, we have shown that tauroursodeoxycholic acid (TUDCA), an endogenous bile
      acid, modulates Abeta-induced apoptosis by interfering with crucial events of the
      mitochondrial pathway. In this study, we examined the role of E2F and p53
      activation in the induction of apoptosis by Abeta, and investigated novel
      molecular targets for TUDCA. The results showed that despite Bcl-2 up-regulation,
      PC12 neuronal cells underwent significant apoptosis after incubation with the
      active fragment Abeta (25-35), as assessed by DNA fragmentation, nuclear
      morphology and caspase-3-like activation. In addition, transcription through the
      E2F-1 promoter was significantly induced and associated with loss of the
      retinoblastoma protein. In contrast, levels of E2F-1, p53 and Bax proteins were
      markedly increased. Overexpression of E2F-1 in PC12 cells was sufficient to
      induce p53 and Bax proteins, as well as nuclear fragmentation. Notably, TUDCA
      modulated Abeta-induced apoptosis, E2F-1 induction, p53 stabilization and Bax
      expression. Further, TUDCA protected PC12 cells against p53- and Bax-dependent
      apoptosis induced by E2F-1 and p53 overexpression, respectively. In conclusion,
      the results demonstrate that Abeta-induced apoptosis of PC12 cells proceeds
      through an E2F-1/p53/Bax pathway, which, in turn, can be specifically inhibited
      by TUDCA, thus underscoring its potential therapeutic use.

PMID- 15255935
TI  - Molecular genetic responses to lysergic acid diethylamide include transcriptional
      activation of MAP kinase phosphatase-1, C/EBP-beta and ILAD-1, a novel gene with
      homology to arrestins.
AB  - We recently demonstrated that the potent hallucinogenic drug lysergic acid
      diethylamide (LSD) dynamically influences the expression of a small collection of
      genes within the mammalian prefrontal cortex. Towards generating a greater
      understanding of the molecular genetic effects of hallucinogens and how they may
      relate to alterations in behavior, we have identified and characterized
      expression patterns of a new collection of three genes increased in expression by
      acute LSD administration. These genes were identified through additional screens
      of Affymetrix DNA microarrays and examined in experiments to assess dose
      response, time course and the receptor mediating the expression changes. The
      first induced gene, C/EBP-beta, is a transcription factor. The second gene, MKP
      1, suggests that LSD activates the MAP (mitogen activated protein) kinase
      pathway. The third gene, ILAD-1, demonstrates sequence similarity to the
      arrestins. The increase in expression of each gene was partially mediated through
      LSD interactions at 5-HT2A (serotonin) receptors. There is evidence of
      alternative splicing at the ILAD-1 locus. Furthermore, data suggests that various
      splice isoforms of ILAD-1 respond differently at the transcriptional level to
      LSD. The genes thus far found to be responsive to LSD are beginning to give a
      more complete picture of the complex intracellular events initiated by
      hallucinogens.

PMID- 15255936
TI  - Examination of the rate of peptide biosynthesis in neuroendocrine cell lines
      using a stable isotopic label and mass spectrometry.
AB  - The biosynthesis of neuroendocrine peptides is typically examined by following
      the rate of appearance of a radioactive amino acid into mature forms of peptides.
      In the present study, we labeled cell lines with L-leucine containing 10
      deuterium residues (d(10)-Leu) and used mass spectrometry to measure the
      biosynthetic rate of gamma-lipotropin in the AtT-20 cell line and insulin in the
      INS-1 cell line. After 3 h of labeling, both peptides show detectable levels of
      the d-labeled form in the cells and media. The relative levels of the d-labeled
      forms are greater in the media than in the cells, consistent with previous
      studies that found that newly synthesized peptides are secreted at a higher rate
      than older peptides under basal conditions. When AtT-20 cells were stimulated
      with KCl or forskolin, the ratio of d- to H-labeled gamma-lipotropin in the
      medium decreased, suggesting that the older peptide was in a compartment that
      could be released upon the appropriate stimulation. Overexpression of proSAAS in
      AtT-20 cells reduced the ratio of d- to H-labeled gamma-lipotropin, consistent
      with the proposed role of proSAAS as an endogenous inhibitor of prohormone
      convertase-1. Labeling with d10-Leu was also used to test whether altering the pH
      of the secretory pathway with chloroquine affected the rate of peptide
      biosynthesis. In AtT-20 cells, 30 microm chloroquine for 3 or 6 h significantly
      reduced the rate of formation of gamma-lipotropin in both cells and media.
      Similarly, INS-1 cells treated with 10, 30, or 60 microm chloroquine for 6 h
      showed a significant decrease in the rate of formation of insulin in both cells
      and media. These results are consistent with the acidic pH optima for peptide
      processing enzymes. Stable isotopic labeling with d10-Leu provides a sensitive
      method to examine the rate of peptide formation in neuroendocrine cell lines.

PMID- 15255938
TI  - Specific localization of the annexin II heterotetramer in brain lipid raft
      fractions and its changes in spatial learning.
AB  - Annexin-II (AII) is a Ca(2+)-dependent phospholipid-binding protein that is
      present in both intracellular and extracellular compartments. In the present
      study AII immunoreactivity was found in a subpopulation of neurons in specific
      brain regions, including the cerebral cortex and the surface of hippocampal
      pyramidal neurons from adult rats. AII from synaptic membranes was detected by
      immunoblotting as multiple species containing the monomer (AII36) and
      heterotetramer (AIIt). AIIt was resistant to beta-mercaptoethanol and
      dithiothreitol in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but
      was completely reduced to monomers (36 kDa) by two-dimensional electrophoresis.
      AIIt resided exclusively in the detergent-resistant lipid rafts concentrated in
      neuronal dendrites, and its recruitment to those structures was enhanced by
      antibody cross-link. AII abundantly distributed on the outer leaflet of neuronal
      membranes and between spaces of neurons appeared to be neuronal adhesive. The
      formation of AIIt required synthesis of sphingolipids and cholesterol, and its
      stability depended on Ca2+. Increases in neuronal activities such as
      depolarization and learning were shown to promote formation of AIIt. Our results
      suggest that, via a dynamic association with dendritic lipid rafts, AII may play
      a role in synaptic signal transduction and remodeling. This probably involves
      focal adhesion and interactions with actin that are associated with brain
      development and memory consolidation.

PMID- 15255937
TI  - The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal
      model of neurodegeneration through a MEK-ERK and Akt-independent mechanism.
AB  - Cerebellar granule neurons undergo apoptosis when switched from a medium
      containing high potassium (HK) to one that has low potassium (LK). LK-induced
      cell death is blocked by GW5074 [5-Iodo-3-[(3,5-dibromo-4-hydroxyphenyl)
      methylene]-2-indolinone], a synthetic drug that inhibits c-Raf activity in vitro.
      GW5074 has no direct effect on the activities of several apoptosis-associated
      kinases when assayed in vitro. In contrast to its effect in vitro, treatment of
      neurons with GW5074 causes c-Raf activation (when measured in vitro in the
      absence of the drug) and stimulates the Raf-MEK-ERK pathway. Treatment of neurons
      with GW5074 also leads to an increase in the activity of B-Raf, which is not
      inhibited by GW5074 in vitro at concentrations at which the drug exerts its
      neuroprotective effect. PD98059 and U0126, two distinct inhibitors of MEK, block
      the activation of ERK by GW5074 but have no effect on its ability to prevent cell
      death. Overexpression of a dominant-negative form of Akt does not reduce the
      efficacy of GW5074, demonstrating an Akt-independent mechanism of action.
      Neuroprotection is inhibited by SN-50, a specific inhibitor of nuclear factor
      kappa B (NF-kappaB) and by the Ras inhibitor S-trans, trans-farnesylthiosalicylic
      acid (FTS) implicating NF-kappaB and Ras in the neuroprotective signaling pathway
      activated by GW5074. In addition to preventing LK-induced apoptosis, treatment
      with GW5074 protects against the neurotoxic effects of MPP+ and methylmercury in
      cerebellar granule neurons, and glutathione depletion-induced oxidative stress in
      cortical neurons. Furthermore, GW5074 prevents neurodegeneration and improves
      behavioral outcome in an animal model of Huntington's disease. Given its
      neuroprotective effect on distinct types of cultured neurons, in response to
      different neurotoxic stimuli, and in an animal model of neurodegeneration, GW5074
      could have therapeutic value against neurodegenerative pathologies in humans.

PMID- 15255939
TI  - Neuronal A1 receptors mediate increase in extracellular kynurenic acid after
      local intrastriatal adenosine infusion.
AB  - The naturally occurring purine nucleoside adenosine has pronounced anticonvulsant
      and neuroprotective properties and plays a neuromodulatory role in the CNS.
      Kynurenic acid (KYNA) is an astrocyte-derived, endogenous neuroinhibitory
      compound, which shares several of adenosine's properties. In a first attempt to
      examine possible interactions between these two biologically active molecules,
      adenosine was focally applied into the striatum of freely moving rats by reverse
      microdialysis, and changes in extracellular KYNA were monitored over time. A 2-h
      infusion of adenosine increased KYNA levels in a dose-dependent manner, with 10
      mm of adenosine causing a twofold elevation within 1 h. This effect was
      reversible and was effectively blocked by coinfusion of the specific A1 adenosine
      receptor antagonist 8-cyclopentyltheophylline (100 microm). In contrast,
      coinfusion of adenosine with MSX-3 (100 microm), an A2A receptor antagonist, did
      not affect the adenosine-induced increase in KYNA levels. Local striatal
      perfusion with the A1 receptor agonist N6-cyclopentyladenosine (100 microm)
      mimicked the effect of adenosine, whereas perfusion with the A2A receptor agonist
      CGS-21680 (100 microm) was ineffective. Finally, we tested the effect of
      adenosine (10 mm) on extracellular KYNA in striata that had been injected with
      quinolinate (60 nmol/1 microL) 7 days earlier. In this neuron-depleted tissue,
      perfusion with adenosine failed to affect extracellular KYNA levels. These data
      demonstrate that adenosine is capable of raising extracellular KYNA in the rat
      striatum by interacting with postsynaptic neuronal A1 receptors. This mechanism
      may result in a synergism between the neurobiological effects of adenosine and
      KYNA.

PMID- 15255940
TI  - Arachidonic acid increases choline acetyltransferase activity in spinal cord
      neurons through a protein kinase C-mediated mechanism.
AB  - Arachidonic acid (AA) plays an important role as a signaling factor in the CNS.
      Therefore, exposure to AA may affect cholinergic neurons in the spinal cord. To
      test this hypothesis, mRNA expression and activity of choline acetyltransferase
      (ChAT) was measured in cultured spinal cord neurons treated with increasing
      concentrations (0.1-10 microm) of AA. Exposure to AA increased mRNA levels and
      activity of ChAT in dose- and time-dependent manners. The most marked effect of
      AA on ChAT expression was observed in spinal cord neurons treated with 10 microm
      AA for 1 h. To study the mechanisms associated with these effects, ChAT mRNA
      levels and activity were measured in cultured spinal cord neurons exposed to AA
      and inhibitors of protein kinase C (PKC), such as 1-(5-isoquinolinesulfonyl)-2
      methylpiperazine dichloride (H-7) and chelerythrine. Inhibition of PKC completely
      prevented an AA-induced increase in ChAT expression. In addition, exposure of
      spinal cord neurons to phorbol-12-myristate-13-acetate (PMA), an activator of
      PKC, mimicked AA-induced stimulation of ChAT activity. The AA-mediated increase
      in ChAT mRNA levels and activity was also prevented by treatments with EGTA,
      indicating the role of calcium metabolism in induction of this enzyme. In
      contrast, treatments with 7-nitroindazole (7-NI, a specific inhibitor of neuronal
      nitric oxide synthase), sodium vanadate (NaV, a non-specific inhibitor of
      phosphatases), and N-acetyl-cysteine (NAC, an antioxidant) had no effect on AA
      induced changes in ChAT activity. The protein synthesis inhibitor cycloheximide
      completely blocked AA-mediated increase in ChAT activity. These results indicate
      that the AA-evoked increase in ChAT activity in spinal cord neurons is mediated
      by PKC, presumably at the transcriptional level.

PMID- 15255941
TI  - Induction of secretory phospholipase A2 in reactive astrocytes in response to
      transient focal cerebral ischemia in the rat brain.
AB  - Although mRNA expression of group IIA secretory phospholipase A2 (sPLA2-IIA) has
      been implicated in responses to injury in the CNS, information on protein
      expression remains unclear. In this study, we investigated temporal and spatial
      expression of sPLA2-IIA mRNA and immunoreactivity in transient focal cerebral
      ischemia induced in rats by occlusion of the middle cerebral artery. Northern
      blot analysis showed a biphasic increase in sPLA2-IIA mRNA expression following
      60-min of ischemia-reperfusion: an early phase at 30 min and a second increase at
      a late phase ranging from 12 h to 14 days. In situ hybridization localized the
      early-phase increase in sPLA2-IIA mRNA to the affected ischemic cortex and the
      late-phase increase to the penumbral area. Besides sPLA2-IIA mRNA, glial
      fibrillary acidic protein (GFAP) and cyclo-oxygenase-2 mRNAs, but not cytosolic
      PLA2, also showed an increase in the penumbral area at 3 days after ischemia
      reperfusion. Immunohistochemistry of sPLA2-IIA indicated positive cells in the
      penumbral area similar to the GFAP-positive astrocytes but different from the
      isolectin B4-positive microglial cells. Confocal microscopy further confirmed
      immunoreactivity of sPLA2-IIA in reactive astrocytes but not in microglial cells.
      Taken together, these results demonstrate for the first time an up-regulation of
      the inflammatory sPLA2-IIA in reactive astrocytes in response to cerebral
      ischemia-reperfusion.

PMID- 15255942
TI  - Role of phospholipase D signaling in ethanol-induced inhibition of carbachol
      stimulated DNA synthesis of 1321N1 astrocytoma cells.
AB  - Inhibition of astrocyte proliferation has been suggested to be an important event
      in the developmental neurotoxicity associated with ethanol. We have previously
      shown that the acetylcholine analog carbachol induces astroglial cell
      proliferation through activation of muscarinic M3 receptors, and that ethanol
      strongly inhibits this effect by inhibiting activation of protein kinase C (PKC)
      zeta and its down-stream effector 70-kDa ribosomal S6 kinase (p70S6K). In this
      study, we investigated whether inhibition by ethanol of this signal transduction
      pathway in 1321N1 human astrocytoma cells may be due, at least in part, to
      inhibition of the formation of the PKC zeta activator phosphatidic acid (PA),
      which is formed by hydrolysis of phosphatidylcholine by phospholipase D (PLD). 1
      Butanol, which is a substrate for PLD and inhibits PA formation, inhibited
      carbachol-induced cell proliferation and the underlying intracellular signaling,
      whereas its analog tert-butanol, which is a poor substrate for PLD, was much less
      effective. In addition, exogenous PAs were able to increase DNA synthesis and to
      activate PKC zeta and p70S6K. Furthermore, in carbachol-stimulated cells, ethanol
      increased the formation of phosphatidylethanol and inhibited the formation of PA.
      Taken together, these results indicate that PLD activation plays an important
      role in carbachol-induced astroglial cell proliferation by generating the second
      messenger PA, which activates PKC zeta. Moreover, the effect of ethanol on
      carbachol-induced proliferation appears to be mediated, at least in part, by its
      ability to interact with PLD leading to a decreased synthesis of PA.

PMID- 15255943
TI  - Increased dopamine release in vivo by estradiol benzoate from the central
      amygdaloid nucleus of Parkinson's disease model rats.
AB  - In addition to the dopaminergic neurons in the nigrostriatal system, the
      properties of dopaminergic neurons in the mesolimbic system, such as the
      amygdala, are also of interest and importance because of their specific
      neuromodulatory effects in the pathophysiology of Parkinson's disease (PD). Using
      the fast cyclic voltammetry (FCV) technique, we present evidence to indicate that
      electrically-evoked dopamine (DA) release from the amygdala, especially the
      central amygdaloid nucleus (CAN), of ovariectomized (OVX) female rats was
      significantly enhanced with increasing doses of estradiol benzoate (EB; 30, 50
      and 100 microg/kg). Impaired DA release from the amygdala of an OVX rat PD model
      can also be increased by EB treatment (50 microg/kg) to a level similar to that
      of controls. The well established neuroprotective effects of estrogen may be
      beneficial for reducing the dysfunction of dopaminergic neurons in mesolimbic
      structures of rat PD models and PD patients.

PMID- 15255944
TI  - Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95.
AB  - The insulin receptor substrate of 53 kDa (IRSp53) is a target of the small GTPase
      cdc42 which is strongly enriched in the postsynaptic density of excitatory
      synapses. IRSp53 interacts with the postsynaptic shank1 scaffolding molecule in a
      cdc42 regulated manner. The functional significance of the cdc42/IRSp53 pathway
      in postsynaptic sites is however, unclear. Here we identify PSD-95 as a second
      synaptic interaction partner of IRSp53. Interaction is mediated by a C-terminal
      PDZ binding motif in IRSp53 and the second PDZ domain of PSD-95. In HEK cells,
      overexpressed IRSp53 induces filopodia and targets PSD-95 into these processes.
      Immunoprecipitation and immunocytochemistry experiments demonstrate that the
      interaction occurs at postsynaptic sites in the brain. By virtue of its PDZ
      binding and SH3 domains, IRSp53 is capable of inducing the formation of a triple
      complex (shank1/IRSp53/PSD-95).

PMID- 15255945
TI  - Increased cerebral uptake and oxidation of exogenous betaHB improves ATP
      following traumatic brain injury in adult rats.
AB  - There is growing evidence of the brain's ability to increase its reliance on
      alternative metabolic substrates under conditions of energy stress such as
      starvation, hypoxia and ischemia. We hypothesized that following traumatic brain
      injury (TBI), which results in immediate changes in energy metabolism, the adult
      brain increases uptake and oxidation of the alternative substrate beta
      hydroxybutyrate (betaHB). Arterio-venous differences were used to determine
      global cerebral uptake of betaHB and production of 14CO2 from [14C]3-betaHB 3 h
      after controlled cortical impact (CCI) injury. Quantitative bioluminescence was
      used to assess regional changes in ATP concentration. As expected, adult sham and
      CCI animals with only endogenously available betaHB showed no significant
      increase in cerebral uptake of betaHB or 14CO2 production. Increasing arterial
      betaHB concentrations 2.9-fold with 3 h of betaHB infusion failed to increase
      cerebral uptake of betaHB or 14CO2 production in adult sham animals. Only CCI
      animals that received a 3-h betaHB infusion showed an 8.5-fold increase in
      cerebral uptake of betaHB and greater than 10.7-fold increase in 14CO2 production
      relative to sham betaHB-infused animals. The TBI-induced 20% decrease in
      ipsilateral cortical ATP concentration was alleviated by 3 h of betaHB infusion
      beginning immediately after CCI injury.

PMID- 15255946
TI  - Metabotropic glutamate and dopamine receptors co-regulate AMPA receptor activity
      through PKA in cultured chick retinal neurones: effect on GluR4 phosphorylation
      and surface expression.
AB  - Glutamate receptor phosphorylation has been implicated in several forms of
      modulation of synaptic transmission. It has been reported that protein kinase A
      (PKA) can phosphorylate the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA) receptor subunit GluR4 on Ser842, both in vitro and in vivo. Here, we
      studied the regulation of GluR4 phosphorylation and intracellular trafficking by
      PKA and by metabotropic receptors coupled to adenylyl cyclase (AC), in cultured
      chick retinal amacrine-like neurones, which are enriched in GluR4. The regulation
      of AMPA receptor activity by PKA and by metabotropic AC-coupled receptors was
      also investigated by measuring the [Ca2+]i response to kainate in Na(+)-free
      medium. Stimulation of AC with forskolin (FSK), or using the selective agonist of
      dopamine D1 receptors (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8
      diol (SKF38393), increased the [Ca2+]i response to kainate, GluR4 phosphorylation
      at Ser842 and GluR4 surface expression. Pre-incubation of the cells with
      (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), an agonist of group
      II metabotropic glutamate receptors (mGluR), which are coupled to inhibition of
      AC, inhibited the effect of FSK and of SKF38393 on AMPA receptor activity, GluR4
      phosphorylation and expression at the plasma membrane. These results indicate
      that there is a functional cross-talk between dopamine D1 receptors and group II
      mGluR in the regulation of GluR4 phosphorylation and AMPA receptor activity. Our
      data show that GluR4 phosphorylation at Ser842 by PKA, and its recruitment to the
      plasma membrane upon phosphorylation, is regulated by metabotropic receptors.

PMID- 15255947
TI  - Relationships between superoxide levels and delayed calcium deregulation in
      cultured cerebellar granule cells exposed continuously to glutamate.
AB  - The relationship is investigated between superoxide levels in single cultured rat
      cerebellar granule neurons exposed continuously to glutamate in low KCl medium
      and the deregulation of cytoplasmic Ca2+. Cells that maintain a regulated
      cytoplasmic-free Ca2+ and mitochondrial polarization in the presence of glutamate
      show no increase in superoxide levels until the onset of cytoplasmic Ca2+
      deregulation. Oxidative stress of mitochondrial origin is readily detectable, as
      the inhibitors rotenone and antimycin A markedly increase superoxide levels with
      no effect on cytoplasmic-free Ca2+. The potent cell-permeant superoxide
      dismutase/catalase mimetic manganese tetrakis (N-ethylpyridinium-2yl) porphyrin,
      MnTE-PyP, abolishes the deregulation-related increase in superoxide but has no
      effect on deregulation itself. A combination of catalase with the free radical
      scavenger 4-hydroxy-TEMPO also fails to reduce deregulation. Following the loss
      of Ca2+ homeostasis nuclei undergo condensation; this morphological change is not
      inhibited by MnTE-PyP and cannot account for the increased ethidium fluorescence.
      Phospholipase A2 inhibitors decrease the deregulation-related increase in
      superoxide without protecting against deregulation. In conclusion, our study
      indicates that deregulation is not caused by NMDA receptor-mediated oxidative
      stress as NMDA receptor activation does not increase superoxide levels until the
      onset of deregulation. Furthermore, the majority of superoxide is produced in the
      cytoplasm rather than in mitochondria.

PMID- 15255948
TI  - GADD34 protein levels increase after transient ischemia in the cortex but not in
      the CA1 subfield: implications for post-ischemic recovery of protein synthesis in
      ischemia-resistant cells.
AB  - Transient cerebral ischemia is a pathological process whereby an irreversible
      suppression of protein synthesis is believed to contribute to the extent of cell
      death in vulnerable neurons. Endoplasmic reticulum (ER) dysfunction has been
      identified as being responsible for ischemia-induced shut-down of translation.
      Recovery from ER dysfunction is facilitated by GADD34, a protein that
      dephosphorylates eukaryotic initiation factor (eIF)2alpha-P and thus reactivates
      protein synthesis. We investigated ischemia-induced changes in GADD34 levels in
      wild-type and Cu2+/Zn2+ SOD (SOD1) over-expressing rats. Transient global
      cerebral ischemia was induced by common carotid artery occlusion. Tissue samples
      were taken from the vulnerable hippocampal CA1 subfield and the resistant
      cerebral cortex of the right and left hemispheres for evaluation of changes in
      gadd34 mRNA and GADD34 protein levels. In wild-type animals, we found
      significantly lower GADD34 levels than in SOD1 transgenes but no differences in
      gadd34 mRNA levels, implying that superoxides regulate gadd34 translation. After
      ischemia, GADD34 protein levels were significantly increased in the cortex but
      not in the CA1 subfield, and these changes occurred earlier in SOD1 transgenic
      than in wild-type animals. The rise in gadd34 mRNA levels did not differ in the
      cortex and CA1 subfield, implying that gadd34 expression is regulated at the
      translational level.

PMID- 15255949
TI  - UCN-01 alters phosphorylation of Akt and GSK3beta and induces apoptosis in six
      independent human neuroblastoma cell lines.
AB  - In this study we evaluated UCN-01, a small molecule that inhibits protein kinases
      by interacting with the ATP-binding site, as a potential anti-cancer agent for
      neuroblastoma. UCN-01 was effective at inducing apoptosis in six neuroblastoma
      cell lines with diverse cellular and genetic phenotypes. 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase
      mediated dUTP nick-end-labeling (TUNEL) assays, detection of active caspase-3 and
      cleaved poly ADP-ribose polymerase (PARP) confirmed that UCN-01 induced
      apoptosis. Cell cycle analysis determined that the UCN-01 treated cells
      accumulated in S phase by 16 h. Unlike vinblastine and docetaxel that increased
      survivin expression, UCN-01 treatment did not increase X-linked inhibitor of
      apoptosis protein (XIAP) and survivin levels. Analysis of specific
      phosphoepitopes on chk1/2, Akt, and GSK3beta following UCN-01 treatment
      determined that there was no significant change in phospho-chk1/2. However, there
      was decreased immunoreactivity at Ser473 and Thr308 of Akt and Ser9 of GSK3beta
      by 4 h indicating that the Akt survival pathway and downstream signalling was
      compromised. Thus, UCN-01 was effective at inducing apoptosis in neuroblastoma
      cell lines.

PMID- 15255950
TI  - Frame-shifted amyloid precursor protein found in Alzheimer's disease and Down's
      syndrome increases levels of secreted amyloid beta40.
AB  - Frame-shifted amyloid precursor protein (APP(+1)), which has a truncated out-of
      frame C-terminus, accumulates in the neuropathological hallmarks of patients with
      Alzheimer's disease pathology. To study a possible involvement of APP(+1) in the
      pathogenesis of Alzheimer's disease, we expressed APP695 and APP(+1) in the
      HEK293 cell-line and studied whether the processing of APP695 was affected.
      APP(+1) is a secretory protein, but high expression of APP695 and APP(+1) results
      in the formation of intracellular aggregate-like structures containing both
      proteins and Fe65, an adaptor protein that interacts with APP695. APP(+1) is
      shown to interact with APP695, suggesting that these structures consist of
      functional protein complexes. Such an interaction can also be anticipated in post
      mortem brains of young Down's syndrome patients without any sign of
      neuropathology. Here we observed APP(+1) immunoreactivity in beaded fibres.
      Additional support for functional consequences on the processing of APP695 comes
      from a 1.4-fold increase in levels of secreted amyloid beta40 in cells co
      expressing APP695 and APP(+1), although APP(+1) itself does not contain the
      amyloid beta sequence. Taken together, these data show that co-expression of
      APP695 and APP(+1) affects the processing of APP695 in a pro-amyloidogenic way
      and this could gradually contribute to Alzheimer's disease pathology, as has been
      implicated in Down's syndrome patients.

PMID- 15255951
TI  - Neuronal expression of myeloperoxidase is increased in Alzheimer's disease.
AB  - Myeloperoxidase, a heme protein expressed by professional phagocytic cells,
      generates an array of oxidants which are proposed to contribute to tissue damage
      during inflammation. We now report that enzymatically active myeloperoxidase and
      its characteristic amino acid oxidation products are present in human brain.
      Further, expression of myeloperoxidase is increased in brain tissue showing
      Alzheimer's neuropathology. Consistent with expression in phagocytic cells,
      myeloperoxidase immunoreactivity was present in some activated microglia in
      Alzheimer brains. However, the majority of immunoreactive material in brain
      localized with amyloid plaques and, surprisingly, neurons including granule and
      pyramidal neurons of the hippocampus. Confirming neuronal localization of the
      enzyme, several neuronal cell lines as well as primary neuronal cultures
      expressed myeloperoxidase protein. Myeloperoxidase mRNA was also detected in
      neuronal cell lines. These results reveal the unexpected presence of
      myeloperoxidase in neurons. The increase in neuronal myeloperoxidase expression
      we observed in Alzheimer disease brains raises the possibility that the enzyme
      contributes to the oxidative stress implicated in the pathogenesis of the
      neurodegenerative disorder.

PMID- 15255952
TI  - Systemic serotonin sulfate in opisthobranch mollusks.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a ubiquitous modulatory neurotransmitter
      with roles as a neurohormone and neurotransmitter. However, few studies have been
      performed characterizing this molecule and its related metabolites in circulating
      fluids. Here, we demonstrate native 5-HT sulfate, but much lower levels of 5-HT,
      in hemolymph of the marine mollusk Pleurobranchaea californica. The metabolite 5
      HT sulfate forms from 5-HT uptake and metabolism in central ganglia of Aplysia
      californica and in the visceral nerve and eye of Pleurobranchaea, but not in
      hemolymph itself. In addition, 5-hydroxyindole acetic acid (5-HIAA), while not
      detected in hemolymph, forms in higher quantities than does 5-HT sulfate in the
      eye and visceral nerve, and gamma-glu-5-HT is also observed in this area but
      never in hemolymph. As systemic 5-HT sulfate appears not to originate from the
      optic region or from systemic 5-HT, 5-HT sulfate likely derives from the nervous
      system. Circulating 5-HT sulfate is at least 10-fold higher during the light
      portion of a 12 : 12-h light/dark cycle than during the dark portion (p <
      0.0007), but there is no obvious trend for free systemic tryptophan (Trp) (p >
      0.3) in Pleurobranchaea. 5-HT in mollusks is associated with general arousal
      state; thus, diurnal systemic changes in a 5-HT catabolite may reflect a
      regulatory role for indole catabolism in behavioral rhythms.

PMID- 15255953
TI  - Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain
      parenchymal and capillary endothelial cells.
AB  - Organic anion transporting polypeptide 3 (oatp3) transports various CNS-acting
      endogenous compounds, including thyroid hormones and prostaglandin E2, between
      extra- and intracellular spaces, suggesting a possible role in CNS function. The
      purpose of this study was to clarify the expression and localization of oatp3 in
      the mouse brain. RT-PCR analysis revealed that oatp3 mRNA is expressed in brain
      capillary-rich fraction, conditionally immortalized brain capillary endothelial
      cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2
      and 5 mRNAs were detected. Immunohistochemical analysis with anti-oatp3 antibody
      suggests that oatp3 protein is localized at the brush-border membrane of mouse
      choroid plexus epithelial cells. Furthermore, intense immunoreactivity was
      detected in neural cells in the border region between hypothalamus and thalamus,
      and in the olfactory bulb. Immunoreactivity was also detected in brain capillary
      endothelial cells in the cerebral cortex. These localizations in the mouse brain
      suggest that oatp3 plays roles in blood-brain and -cerebrospinal fluid barrier
      transport of organic anions and signal mediators, and in hormone uptake by neural
      cells.

PMID- 15255954
TI  - Beta-naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by
      inhibiting autocrine interleukin-6.
AB  - Regulation of astrocyte differentiation is a key process in the development of
      the central nervous system (CNS), and disturbance of the differentiation can lead
      to brain system dysfunction. Here we show that beta-naphthoflavone (betaNF), an
      agonist of the aryl hydrocarbon receptor (AhR), disturbed the cAMP-induced
      astrocytic differentiation of C6 glioma by inhibiting autocrine interleukin-6 (IL
      6). Treatment of cells with betaNF reduced the induction of an astrocyte marker
      glial fibrillary acidic protein (GFAP). This was caused by the inactivation of
      its upstream transcription factor signal transducer and activator of
      transcription 3 (STAT3) by betaNF. In addition, betaNF attenuated the induction
      of the IL-6 gene, which leads to the activation of STAT3. Most importantly, the
      inhibitory effect of betaNF on GFAP promoter activity was recovered by the
      addition of recombinant IL-6. Taken together, these results indicate that the
      inhibitory effect of betaNF on IL-6 induction suppresses STAT3 activation. These
      processes subsequently lead to the attenuation of GFAP induction.

PMID- 15255955
TI  - Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice
      following repetitive concussive brain injury.
AB  - Traumatic brain injury is a well-recognized environmental risk factor for
      developing Alzheimer's disease. Repetitive concussive brain injury (RCBI)
      exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and
      deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated
      the effects of vitamin E on these four parameters in Tg2576 mice following RCBI.
      Eleven-month-old mice were randomized to receive either regular chow or chow
      supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24
      h apart) using a modified controlled cortical impact model of closed head injury.
      The same dietary regimens were maintained up to 8 weeks post-injury, when the
      animals were killed for biochemical and immunohistochemical analyses after
      behavioral evaluation. Vitamin E-treated animals showed a significant increase in
      brain vitamin E levels and a significant decrease in brain lipid peroxidation
      levels. After RBCI, compared with the group on regular chow, animals receiving
      vitamin E did not show the increase in Abeta peptides, and had a significant
      attenuation of learning deficits. This study suggests that the exacerbation of
      brain oxidative stress following RCBI plays a mechanistic role in accelerating
      Alphabeta accumulation and behavioral impairments in the Tg2576 mice.

PMID- 15255956
TI  - The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite
      'scavenger'?
AB  - Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown
      to stimulate N-methyl-D-aspartate (NMDA) receptors to enhance long-term
      potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels
      of H2S in the brain are reported to range between 10 and 160 microm. Considerably
      lower H2S levels are reported in the brains of Alzheimer's disease (AD) patients,
      where levels of brain protein nitration (probably mediated by peroxynitrite) are
      markedly increased. Activation of NMDA receptors leads to intracellular tyrosine
      nitration by peroxynitrite. Because H2S and peroxynitrite are important mediators
      in brain function and disease, we investigated the effects of the H2S 'donor',
      sodium hydrogen sulfide (NaSH) on peroxynitrite-mediated damage to biomolecules
      and to cultured human SH-SY5Y cells. H2S significantly inhibited peroxynitrite
      mediated tyrosine nitration and inactivation of alpha1-antiproteinase to a
      similar extent to reduced glutathione at each concentration tested (30-250
      microm). H2S also inhibited peroxynitrite-induced cytotoxicity, intracellular
      protein nitration and protein oxidation in human neuroblastoma SH-SY5Y cells.
      These data suggest that H2S has the potential to act as an inhibitor of
      peroxynitrite-mediated processes in vivo and that the potential antioxidant
      action of H2S deserves further study, given that extracellular GSH levels in the
      brain are very low.

PMID- 15255957
TI  - Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary
      gland initiation in mouse embryos.
AB  - Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and
      the same gene families have been implicated in mammary gland development. Here we
      explore how these genes act together in mammary gland initiation. We compared
      expression of Tbx3, the gene associated with the human condition ulnar-mammary
      syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase
      Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by
      sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a
      transcription factor mediating Wnt signalling and the earliest gene so far known
      to be expressed in mammary gland development. We found that Tbx3 is expressed
      earlier than Lef1 and that Pyst1 is also expressed early but only transiently.
      Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that
      the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with
      expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8
      and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17
      in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse
      embryos, at a stage just prior to mammary bud initiation, induce expression of
      Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead.
      Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and
      Lef1 expression, supporting the idea that FGFR1 signalling is required for early
      mammary gland initiation. We also showed that blocking Wnt signalling abolishes
      Tbx3 expression but not Pyst1 expression. These data, taken together with
      previous findings, suggest a model in which Tbx3 expression is induced and
      maintained in early gland initiation by both Wnt and Fgf signalling through
      FGFR1.

PMID- 15255958
TI  - Immunohistochemical localization of the bone morphogenetic protein receptors in
      the porcine ovary.
AB  - The bone morphogenetic protein (BMP) family is emerging as playing a crucial role
      in regulating normal follicle growth and determining ovulation rate. BMPs exert
      their effects via BMP receptors (BMPR-IA, -IB and -II). However, there is a
      paucity of information relating to the expression of the BMPRs within the ovary
      of large polyovular species such as the pig. Furthermore, there is a lack of
      information on the expression of BMPRs by fetal ovaries of any species. The
      purpose of this study was to investigate temporal and spatial expression of the
      BMPRs in the porcine ovary, at different developmental stages.
      Immunohistochemistry for BMPR-IA, BMPR-IB and BMPR-II was performed using
      sections from paraffin wax-embedded ovaries, obtained from fetal (n = 15),
      prepubertal (n = 3) and cycling postpubertal (n = 4) pigs. Results confirmed the
      presence of all three receptors in the fetal egg nests and in the granulosa cell
      layer of follicles ranging from primordial to late antral stages. Immunostaining
      was also observed in oocytes, theca layer, corpus luteum and ovarian surface
      epithelium. The expression of BMPRs by fetal ovaries may be related to follicle
      formation, whereas expression in pre- and post-pubertal animals indicates BMPs
      are involved in regulating porcine ovarian follicle growth.

PMID- 15255959
TI  - The appearance and distribution of mature T and B cells in the developing immune
      tissues of the stripe-faced dunnart (Sminthopsis macroura).
AB  - This paper describes the initial appearance and distribution of mature T and B
      cells in the developing immune tissues of the stripe-faced dunnart (Sminthopsis
      macroura) based on the use of species cross-reactive antibodies to the lymphocyte
      cell surface markers CD3, CD5 and CD79b. At birth no mature T or B cells were
      detected in the liver or bone marrow using anti-CD3, anti-CD5 or anti-CD79b
      antibodies. T cells were detected in the thymus with anti-CD3 by day 12 and anti
      CD5 by day 50 postpartum, and T cells in the spleen were detected by day 43 and
      day 80 postpartum using anti-CD3 and anti-CD5, respectively. B cells were
      observed in the dunnart spleen by 43 days after birth. CD3- and CD79b-positive
      cells were detected in the lymph nodes by 50 days and CD5 by day 15 after birth,
      and in the gut-associated lymphoid tissues by day 50 and anti-CD5 by day 57
      postpartum. The development and distribution of T and B cells in the immune
      tissues of dunnart pouch young is similar to that described in other marsupial
      species. Low numbers or absence of mature lymphocytes in immune tissues of early
      pouch young dunnarts further support the proposition that young marsupials are
      reliant on non-specific defence strategies and/or maternal strategies for a
      significant period of their time of development in the pouch.

PMID- 15255960
TI  - The development and distribution of the interstitial cells of Cajal in the
      intestine of the equine fetus and neonate.
AB  - This study set out to determine the pattern of development and distribution of
      the interstitial cells of Cajal (ICC) in the intestinal tract of the equine fetus
      and neonate. Intestinal tissue samples from 12 naturally aborted equine fetuses
      and three euthanized neonates were collected and fixed in formalin prior to
      applying standard immunohistochemical labelling techniques targeting the c-Kit
      protein of the ICC. At 6 months of gestation, a network of ICC was present in the
      myenteric plexus region of both the small and the large intestine. ICC were also
      present within the circular muscle layer. In the large intestine, a proximal to
      distal gradient of distribution was evident, with few ICC observed in the more
      distal parts of the large intestine in the younger fetuses compared with the near
      term animals. A transmural gradient of distribution was also evident within the
      large intestine, with the most luminal part of the muscularis externa being the
      last area to be colonized by ICC. This region did not appear fully developed
      until the early neonatal period. An increased density of ICC was noted throughout
      the large intestine in the regions of the taenial bands in all animals. This
      study is the first to describe ICC development and distribution in the equine
      fetus and neonate.

PMID- 15255961
TI  - Distribution patterns of immunocompetent cells in the pregnant mouse uteri
      carrying allogeneic mouse and xenogeneic vole embryos.
AB  - Mouse and vole embryos were allogeneically and xenogeneically transferred into
      pseudopregnant CD-1 and immunodeficient (scid) female mice, and we investigated
      the distribution of immunocompetent cells, uterine natural killer (uNK) cells,
      mast cells and macrophages, in the implantation sites on days 6, 7 and 8 of
      gestation. The survival rate of the vole embryos decreased gradually with
      increased gestation, but the rate was higher in the scid uteri than in the CD-1
      mice. The number of uNK cells increased markedly at the mesometrial triangle and
      the outer decidual area in the CD-1 uteri containing vole embryos; by contrast,
      scid uteri having vole embryos showed almost the same number as those having
      mouse embryos. Mast cells were present in large numbers at the myometrium, but
      rarely in the decidua in all types of pregnant uteri. Cells at the myometrium
      were more numerous in xenogeneic than in allogeneic transfer. Many mast cells
      appeared in the inner decidua where xenogeneically transferred vole embryos were
      dead and aborted. Macrophages were present in the outer decidua and myometria in
      all types of pregnant uteri, and their distribution pattern did not change even
      in aborted uterine sites. These results suggest: (1) the response of macrophages
      to dead embryos is completely inhibited, (2) uNK cells and mast cells increase
      near dead and aborted embryos, and (3) the increment in uNK cells responding to
      xenogeneic embryos is suppressed in scid mice, and the suppression may contribute
      partly to survival of the embryos.

PMID- 15255962
TI  - Morphological study of the perireticular nucleus in human fetal brains.
AB  - Abstract The perireticular nucleus consists of scattered neurons that are located
      in the internal capsule. The presence of perireticular neurons in the rat,
      ferret, cat and human has been described previously. Evidence suggests that the
      perireticular neurons in various species decrease in number with increasing
      gestation, but in humans this finding has not been supported by quantitative
      data. This study aimed to investigate (1) the morphology of the human fetal
      perireticular neurons, (2) the average number of perireticular neurons within the
      anterior and posterior crus of the internal capsule per unit area, and (3) the
      magnitude and the stage of neuronal loss in the human perireticular nucleus
      subsequent to maturation. Nissl-stained sections of the internal capsule of human
      fetal brains of 24, 26.5, 32, 35, 37 and 39 weeks of gestation showed a number of
      clearly distinguishable large perireticular and small microglia cells. A regular
      increase of both perireticular and microglial cells was observed up to 32 weeks
      of gestation, after which a dramatic reduction in the number of both
      perireticular and microglia cells was observed. The average number of
      perireticular and the microglia cells per unit area, located within the posterior
      crus, was more than in the anterior crus of the internal capsule. In the adult,
      no perireticular neurons were detected within the internal capsule. The results
      show that perireticular neurons are not restricted to the region lateral to the
      thalamus and medial to the globus pallidus (posterior crus) but are also present
      at the region lateral to the caudate nucleus and medial to the globus pallidus
      (anterior crus).

PMID- 15255963
TI  - Connections between the facial, vestibular and cochlear nerve bundles within the
      internal auditory canal.
AB  - The vestibular, cochlear and facial nerves have a common course in the internal
      auditory canal (IAC). In this study we investigated the average number of nerve
      fibres, the average cross-sectional areas of the nerves and nerve fibres, and the
      apparent connections between the facial, cochlear and vestibular nerve bundles
      within the IAC, using light and scanning electron microscopy. The anatomical
      localization of the nerves within the IAC was not straightforward. The general
      course showed that the nerves rotated anticlockwise in the right ear from the
      inner ear end towards the brainstem end and vice versa for the left ear. The
      average number of fibres forming vestibular, cochlear, and facial nerves was not
      constant during their courses within the IAC. The superior and the inferior
      vestibular nerves showed an increase in the number of nerve fibres from the inner
      ear end towards the brainstem end of the IAC, whereas the facial and the cochlear
      nerves showed a reduction in the number of fibres. This suggests that some of the
      superior and inferior vestibular nerve bundles may receive fibres from the facial
      and/or cochlear nerves. Scanning electron microscopic evaluations showed superior
      vestibular-facial and inferior vestibular-cochlear connections within the IAC,
      but no facial-cochlear connections were observed. Connections between the nerves
      of the IAC can explain the unexpected vestibular disturbances in facial paralysis
      or persistence of tinnitus after cochlear neurectomy in intractable tinnitus
      cases. The present study offers morphometric and scanning electron microscopic
      data on the fibre connections of the nerves of the IAC.

PMID- 15255965
TI  - Adult stem cell plasticity: will engineered tissues be rejected?
AB  - The dogma that adult tissue-specific stem cells remain committed to supporting
      only their own tissue has been challenged; a new hypothesis, that adult stem
      cells demonstrate plasticity in their repertoires, is being tested. This is
      important because it seems possible that haematopoietic stem cells, for example,
      could be exploited to generate and perhaps deliver cell-based therapies deep
      within existing nonhaematopoietic organs. Much of the evidence for plasticity
      derives from histological studies of tissues from patients or animals that have
      received grafts of cells or whole organs, from a donor bearing (or lacking) a
      definitive marker. Detection in the recipient of appropriately differentiated
      cells bearing the donor marker is indicative of a switch in phenotype of a stem
      cell or a member of a transit amplifying population or of a differentiated cell.
      In this review, we discuss evidence for these changes occurring but do not
      consider the molecular basis of cell commitment. In general, the extent of
      engraftment is low but may be increased if tissues are damaged. In model systems
      of liver regeneration, the repeated application of a selection pressure increases
      levels of engraftment considerably; how this occurs is unclear. Cell fusion plays
      a part in regeneration and remodelling of the liver, skeletal muscle and even
      regions of the brain. Genetic disease may be amenable to some forms of cell
      therapy, yet immune rejection will present challenges. Graft-vs.-host disease
      will continue to present problems, although this may be avoided if the cells were
      derived from the recipient or they were tolerized. Despite great expectations for
      cellular therapies, there are indications that attempts to replace missing
      proteins could be confounded simply by the development of specific immunity that
      rejects the new phenotype.

PMID- 15255966
TI  - Pathological and immunological profiles of rat tuberculosis.
AB  - To investigate the pathological and immunological profiles of rat tuberculosis,
      Lewis female rats were infected aerially with Mycobacterium tuberculosis.
      Histopathology, immunological profiles of mononuclear cells from M. tuberculosis
      infected rat lung tissue, and the expression patterns of cytokine and iNOS mRNAs
      were examined over time. M. tuberculosis induced granulomatous lesions in the
      lungs, spleen, lymph nodes and liver, but these lesions lacked central necrosis.
      Multinucleate giant cells were observed in late-phase tuberculosis. CD4(+) and
      CD8(+) T cells increased with time and reached a peak 5 weeks after infection,
      decreasing gradually thereafter. ED1 antigen, suggestive of alveolar macrophages,
      was expressed at a high level in early phase tuberculosis and remained at the
      same level even in the late phase. OX62 antigen increased gradually and reached a
      peak 5 weeks after infection. Interferon-gamma, tumour necrosis factor-alpha and
      iNOS mRNAs were expressed strongly over time, but their expression decreased 12
      weeks after infection. Because rat tuberculosis is very similar to murine
      tuberculosis and it is easy to obtain mononuclear cells from M. tuberculosis
      infected rat lung tissue, the rat tuberculosis model appears to be suitable for
      immunological studies in vivo.

PMID- 15255967
TI  - In situ analysis of lung antigen-presenting cells during murine pulmonary
      infection with virulent Mycobacterium tuberculosis.
AB  - Scarce information exists about the role of lung antigen-presenting cells (APCs)
      in vivo during pulmonary tuberculosis. As APCs activate cellular immunity,
      following intratracheal inoculation with virulent Mycobacterium tuberculosis, we
      assessed in situ lung APC recruitment, distribution, granuloma involvement,
      morphology and mycobacterial burden by using MHC-CII, CD14, scavenger receptor
      class A (SRA), the murine dendritic cell (DC)-restricted marker CD11c and Ziehl
      Neelsen staining. CD11c(+) DC and CD14(+) cell recruitment into lungs appeared by
      day 14, continuing until day 60. MHC-CII(+) cells increased since day 7,
      persisting until day 60. Thus, virulent mycobacteria delays (14-21 days) lung APC
      recruitment compared to model antigens and nonvirulent bacilli (24-48 h).
      Regarding granuloma constitution, highly bacillary CD14(+) and SRA(+) cells were
      centrally located. MHC-CII(+) cells were more peripheral, with less mycobacteria.
      CD11c(+) cells were heterogeneously distributed within granulomas, with scarce
      bacilli. When labelling lung suspensions for MHC-CII and classifying cells as
      macrophages or DC, then staining for Ziehl-Neelsen, a remarkable segregation was
      found regarding bacillary burden. Most macrophage-like cells contained numerous
      bacilli, while DC had no or scarce mycobacteria. This implies differential APC
      contributions in situ during pulmonary tuberculosis regarding mycobacterial
      uptake, granuloma involvement and perhaps bacillary growth.

PMID- 15255968
TI  - Activity of lung neutrophils and matrix metalloproteinases in cyclophosphamide
      treated mice with experimental sepsis.
AB  - Sepsis in patients receiving chemotherapy may result in acute respiratory
      distress syndrome, despite decreased number of blood neutrophils
      [polymorphonuclear neutrophils (PMNs)]. In the present study, we investigated the
      correlation of cyclophosphamide (CY)-induced neutropenia with the destructive
      potential of lung PMN in respect to formation of septic acute lung injury (ALI).
      Mice were treated with 250 mg/kg of CY or saline (control) and subjected to cecal
      ligation and puncture (CLP) or sham operation. ALI was verified by histological
      examination. Lung PMNs and matrix metalloproteinases (MMPs) were assessed by flow
      cytometry and gelatin zymography. CLP in CY-treated mice induced a typical lung
      injury. Despite profound neutropenia, CY treatment did not attenuate CLP-induced
      ALI. This might relate to only a partial suppression of PMN: CY has significantly
      reduced PMN influx into the lungs (P = 0.008) and suppressed their oxidative
      metabolism, but had no suppressive effect on degranulation (P = 0.227) and even
      induced MMP-9 activity (P = 0.0003). In CY-untreated animals, peak of CLP-induced
      ALI coincided with massive PMN influx (P = 0.013), their maximal degranulation (P
      = 0.014) and activation of lung MMP-9 (P = 0.002). These findings may indicate an
      important role of the residual lung PMN and activation of MMP-9 in septic lung
      injury during CY chemotherapy.

PMID- 15255969
TI  - Metalloproteinases, insulin-like growth factor-I and its binding proteins in
      aortic aneurysm.
AB  - Abdominal aortic aneurysm is accompanied by the impairment of collagen metabolism
      in arterial wall. Metalloproteinases and collagen-stimulating factors play an
      important role in the maintenance of balance between collagen biosynthesis and
      degradation in tissues. Insulin-like growth factor-I (IGF-I) plays a major role
      in the stimulation of collagen biosynthesis. Its activity and bioavailability to
      target cells are modulated by IGF binding proteins (IGFBPs). The potential role
      of these factors in the mechanism of collagen metabolism deregulation in aortic
      aneurysm is the purpose of this study. Therefore, we have compared the content of
      collagen, gelatinolytic activity, IGF-I, IGFBP-1 and IGFBP-3 in normal human
      aorta and aortic aneurysm. The content of hydroxyproline (representing collagen
      content) in the proteins of aortic aneurysm was found to be similar to that found
      in normal aorta. Taking into account that some of the hydroxyproline may be
      derived from collagen degradation products (CDPs), they were separated and
      hydroxyproline was determined. It has been found that CDP-derived hydroxyproline
      content in aortic aneurysm was increased as compared with normal aorta,
      suggesting an increased collagen degradation. In contrast, zymography showed a
      decrease of collagenolytic activity in aortic aneurysm tissue, but an increase in
      mural thrombus, compared to respective controls. IGF-I concentration in aortic
      aneurysm was decreased, while the concentrations of BP-1 and BP-3 were both
      increased compared to control. The data suggest that increased collagen
      degradation in aortic aneurysm is due to the increase in collagenolytic activity
      in mural thrombus accompanying aneurysm tissue. It suggests that the mural
      thrombus may play a critical role in the pathogenesis of abdominal aortic
      aneurysm.

PMID- 15255970
TI  - A central role for the mast cell in early phase vasculitis in the Brown Norway
      rat model of vasculitis: a histological study.
AB  - Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2
      dominated autoimmunity with raised immunoglobulin E concentrations and gut
      vasculitis, both of which are T-cell dependent, peak at 14 days after starting
      HgCl(2) and then spontaneously resolve. If animals are re-challenged with HgCl(2)
      6 weeks after initial exposure, they are resistant to autoimmunity, developing
      only attenuated disease. Recently, a separate phase of early caecal vasculitis
      was described beginning 24 h after initiating HgCl(2) and prior to caecal entry
      of T cells. Previous work suggested this early vasculitis was alpha beta T-cell
      independent and implied a role for mast cells. We further tested this hypothesis
      by performing a histological study during the first 93 h following HgCl(2)
      challenge defining the precise relationship between gut mast cell degranulation
      and appearing caecal vasculitis. We also studied whether early caecal vasculitis
      enters a resistant phase upon re-challenge with HgCl(2). We show a direct
      correlation between mast cell degranulation and early caecal vasculitis following
      initial HgCl(2) challenge. We demonstrate resistance to re-challenge in this
      phase of injury, with results at re-challenge also showing a correlation between
      mast cell degranulation and early caecal injury.

PMID- 15255972
TI  - Identification of a novel brain-specific and Reelin-regulated gene that encodes a
      protein colocalized with synapsin.
AB  - We carried out a screening of genes that are differentially expressed in normal
      mice and reeler mutants and are characterized by abnormal neuronal migration and
      neurite deployment due to defective Reelin signalling. A novel gene,
      provisionally named C61, was overexpressed in Reelin-deficient embryonic mouse
      brain RNA. C61 encodes a 3.7 kb mRNA that is brain specific and developmentally
      regulated, with predominant expression in differentiating neurons. The predicted
      protein is 664 amino acids long, and contains LAG1 and Ezrin/Radixin/Moesin
      Myosin-Filament motifs, suggesting that it may function as an intracellular
      adaptor. From E14.5 to birth, C61 was highly expressed in all neuronal
      differentiation fields, with the highest signal in the telencephalic cortical
      plate and mitral cells in the olfactory bulb. When expressed as a GFP fusion
      protein in transfected non-neuronal cells and primary neurons, this protein
      localizes, respectively, to the nuclear membrane or axonal outgrowths, indicating
      a function in axonal traffic or signalling.

PMID- 15255973
TI  - Flies lacking all synapsins are unexpectedly healthy but are impaired in complex
      behaviour.
AB  - Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been
      proposed to fine-regulate neurotransmitter release by phosphorylation-dependent
      control of synaptic vesicle motility. However, the consequences of a total lack
      of all synapsin isoforms due to a knock-out of all three mouse synapsin genes
      have not yet been investigated. In Drosophila a single synapsin gene encodes
      several isoforms and is expressed in most synaptic terminals. Thus the targeted
      deletion of the synapsin gene of Drosophila eliminates the possibility of
      functional knock-out complementation by other isoforms. Unexpectedly, synapsin
      null mutant flies show no obvious defects in brain morphology, and no striking
      qualitative changes in behaviour are observed. Ultrastructural analysis of an
      identified 'model' synapse of the larval nerve muscle preparation revealed no
      difference between wild-type and mutant, and spontaneous or evoked excitatory
      junction potentials at this synapse were normal up to a stimulus frequency of 5
      Hz. However, when several behavioural responses were analysed quantitatively,
      specific differences between mutant and wild-type flies are noted. Adult
      locomotor activity, optomotor responses at high pattern velocities, wing beat
      frequency, and visual pattern preference are modified. Synapsin mutant flies show
      faster habituation of an olfactory jump response, enhanced ethanol tolerance, and
      significant defects in learning and memory as measured using three different
      paradigms. Larval behavioural defects are described in a separate paper. We
      conclude that Drosophila synapsins play a significant role in nervous system
      function, which is subtle at the cellular level but manifests itself in complex
      behaviour.

PMID- 15255974
TI  - Trophic support delays but does not prevent cell-intrinsic degeneration of
      neurons deficient for munc18-1.
AB  - The stability of neuronal networks is thought to depend on synaptic transmission
      which provides activity-dependent maintenance signals for both synapses and
      neurons. Here, we tested the relationship between presynaptic secretion and
      neuronal maintenance using munc18-1-null mutant mice as a model. These mutants
      have a specific defect in secretion from synaptic and large dense-cored vesicles
      [Verhage et al. (2000), Science, 287, 864-869; Voets et al. (2001), Neuron, 31,
      581-591]. Neuronal networks in these mutants develop normally up to synapse
      formation but eventually degenerate. The proposed relationship between secretion
      and neuronal maintenance was tested in low-density and organotypic cultures and,
      in vivo, by conditional cell-specific inactivation of the munc18-1 gene.
      Dissociated munc18-1-deficient neurons died within 4 days in vitro (DIV).
      Application of trophic factors, insulin or BDNF delayed degeneration up to 7 DIV.
      In organotypic cultures, munc18-1-deficient neurons survived until 9 DIV. On
      glial feeders, these neurons survived up to 10 DIV and 14 DIV when insulin was
      applied. Co-culturing dissociated mutant neurons with wild-type neurons did not
      prolong survival beyond 4 DIV, but coculturing mutant slices with wild-type
      slices prolonged survival up to 19 DIV. Cell-specific deletion of munc18-1
      expression in cerebellar Purkinje cells in vivo resulted in the specific loss of
      these neurons without affecting connected or surrounding neurons. Together, these
      data allow three conclusions. First, the lack of synaptic activity cannot explain
      the degeneration in munc18-1-null mutants. Second, trophic support delays but
      cannot prevent degeneration. Third, a cell-intrinsic yet unknown function of
      munc18-1 is essential for prolonged survival.

PMID- 15255975
TI  - Voltage-gated K+ current: a marker for apoptosis in differentiating neuronal
      progenitor cells?
AB  - We investigated apoptosis during early stages of in vitro differentiation of
      neuronal precursors generated by embryonic day 14 (E14) mouse striata stem cells.
      Differentiation was in conditions of suboptimal growth factor supply. Apoptosis
      reached 10-15% of cells and affected proliferating as well as postmitotic cells,
      including TUJ1-positive cells. Inhibition of apoptosis led to an increased
      proportion of TUJ1-positive cells generated by stem cells. K(+) current was
      reported to be related to apoptosis. Outward K(+) currents were present in
      differentiating neuronal precursors that were consistent with delayed rectifier
      and transient A-type currents. The amplitude of the delayed rectifier current
      varied during the first 4 days of stem cell differentiation. Current amplitude
      was greatly increased in the presence of staurosporine but reduced at elevated
      extracellular K(+) concentration. In addition, the amplitude of the current was
      significantly diminished by inhibiting several caspases, but not caspase 8. In
      Bax knock-out transgenic neuronal precursors, K(+) current was not decreased
      after the first day but at later stages of cell differentiation. At this early
      stage, apoptosis of proliferating cells and of TUJ1-positive cells was not
      reduced by the absence of Bax, but was by caspase 9 inhibition. Thus, activation
      of a delayed rectifier K(+) current in differentiating stem cells is related to
      apoptosis. Recordings of this current revealed that apoptosis at early stages of
      neuronal differentiation occurred in two phases that did not exhibit similar
      dependence on the proapoptotic protein Bax and that probably used different
      pathways.

PMID- 15255976
TI  - Stimulation of N-methyl-D-aspartate receptors, AMPA receptors or metabotropic
      glutamate receptors leads to rapid internalization of AMPA receptors in cultured
      nucleus accumbens neurons.
AB  - In hippocampus and other regions, alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) receptors are inserted into synapses during long-term
      potentiation and removed during long-term depression. However, little is known
      about regulation of AMPA receptor trafficking in the nucleus accumbens (NAc),
      despite growing evidence that glutamate-dependent forms of plasticity in the NAc
      contribute to drug addiction. Using postnatal rat NAc cultures and an
      immunocytochemical method that selectively detects newly internalized GluR1, we
      studied the regulation of AMPA receptor internalization in NAc neurons by
      glutamate agonists. Newly internalized GluR1 was detected during 15 or 30 min of
      incubation at room temperature, indicating a basal rate of GluR1 turnover. The
      rate of GluR1 internalization was increased by glutamate (50 microM) within 5 min
      of its addition. Glutamate-induced GluR1 internalization was partially blocked by
      either an AMPA receptor antagonist (CNQX; 20 microM) or an N-methyl-D-aspartate
      (NMDA) receptor antagonist (APV; 50 microM). Both NMDA (50 microM) and AMPA (50
      microM) increased GluR1 internalization in a Ca(2+)-dependent manner. The NMDA
      effect was blocked by APV while the AMPA effect was blocked by APV or CNQX. We
      interpret these findings to suggest that NMDA and AMPA ultimately trigger GluR1
      internalization through the same NMDA receptor-dependent pathway. The effect of
      glutamate was also partially blocked by the group 1 metabotropic glutamate
      receptor antagonist N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide
      (PHCCC; 50 microM), while the group 1 agonist 3,5-dihydroxyphenylglycine (DHPG;
      50 microM) stimulated GluR1 internalization. These data suggest that AMPA
      receptors on NAc neurons may be subject to rapid regulation of their surface
      expression in response to changes in the activity of glutamate inputs from
      cortical and limbic regions.

PMID- 15255977
TI  - Anatomical and functional evidence for a role of arginine-vasopressin (AVP) in
      rat olfactory epithelium cells.
AB  - The olfactory epithelium (OE) is composed of olfactory sensory neurons (OSNs) and
      sustentacular cells; it lies in the nasal cavity where it is protected by a thin
      mucus layer. The finely regulated composition of this mucus provides OSN with a
      suitable ionic environment. To maintain the functional integrity of the
      epithelium despite permanent physical, chemical and microbial aggressions, both
      OSNs and surrounding sustentacular cells are continuously renewed from globose
      basal cells. Moreover, the sense of smell is involved in so numerous behaviours
      (feeding, reproduction, etc.) that it has to cross-talk with the endocrine and
      neuroendocrine systems. Thus, besides its sensory function, the olfactory
      epithelium is thought to undergo a lot of complex regulatory processes. We
      therefore studied the effects of various neuropeptides on primary cultures of
      Sprague-Dawley rat olfactory epithelium cells. We found that arginine-vasopressin
      (AVP) triggered a robust, dose-dependent calcium increase in these cells. The
      cell response was essentially ascribed to the V1a AVP receptor, whose presence
      was confirmed by RT-PCR and immunolabelling. In the culture, V1a but not V1b
      receptors were present, mainly localized in neurons. In the epithelium, both
      subtypes were found differentially distributed. V1a-R were localized mainly in
      globose basal cells and at the apical side of the epithelium, in the area of the
      dendritic knobs of OSNs. V1b-R were strongly associated with Bowman's gland cells
      and globose basal cells. These localizations suggested potential multifaceted
      roles of a hormone, AVP, in the olfactory epithelium.

PMID- 15255978
TI  - Axonal injury-dependent induction of the peripheral benzodiazepine receptor in
      small-diameter adult rat primary sensory neurons.
AB  - The peripheral benzodiazepine receptor (PBR), a benzodiazepine but not gamma
      aminobutyric acid-binding mitochondrial membrane protein, has roles in steroid
      production, energy metabolism, cell survival and growth. PBR expression in the
      nervous system has been reported in non-neuronal glial and immune cells. We now
      show expression of both PBR mRNA and protein, and the appearance of binding of a
      synthetic ligand, [(3)H]PK11195, in dorsal root ganglion (DRG) neurons following
      injury to the sciatic nerve. In naive animals, PBR mRNA, protein expression and
      ligand binding are undetectable in the DRG. Three days after sciatic nerve
      transection, however, PBR mRNA begins to be expressed in injured neurons, and 4
      weeks after the injury, expression and ligand binding are present in 35% of L4
      DRG neurons. PBR ligand binding also appears after injury in the superficial
      dorsal horn of the spinal cord. The PBR expression in the DRG is restricted to
      small and medium-sized neurons and returns to naive levels if the injured
      peripheral axons are allowed to regrow and reinnervate targets. No non-neuronal
      PBR expression is detected, unlike its putative endogenous ligand the diazepam
      binding inhibitor (DBI), which is expressed only in non-neuronal cells, including
      the satellite cells that surround DRG neurons. DBI expression does not change
      with sciatic nerve transection. PBR acting on small-calibre neurons could play a
      role in the adaptive survival and growth responses of these cells to injury of
      their axons.

PMID- 15255979
TI  - Mechanism of GABA receptor-mediated inhibition of spontaneous GABA release onto
      cerebellar Purkinje cells.
AB  - gamma-Aminobutyric acid (GABA)(B) receptor-mediated modulation of spontaneous
      GABA release onto Purkinje cells was investigated in cerebellar slices from 3- to
      5-week-old mice. The GABA(B) receptor agonists baclofen and CGP 44533 each
      reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs),
      with no significant effect on mIPSC amplitude; together, consistent with a
      presynaptic site of action. The GABA(B) receptor antagonist CGP 55845 blocked
      baclofen-induced inhibition. The sulphydryl alkylating agent N-ethylmaleimide
      occluded baclofen effects, implicating G(i/o) subunits in mediating a GABA(B) G
      protein-coupled receptor pathway. Baclofen-induced inhibition persisted in the
      presence of Ba(2+), a blocker of K(+) channels, and Cd(2+), a blocker of Ca(2+)
      channel-mediated GABA release. Application of nominally Ca(2+)-free extracellular
      solutions reduced mIPSC frequency and amplitude; however, baclofen produced a
      significant inhibition in mIPSC frequency, further suggesting that this pathway
      was independent of Ca(2+) influx. Spontaneous GABA release was increased by the
      adenylate cyclase activator, forskolin, and the phorbol ester, phorbol 12,13
      dibutyrate. However, baclofen-induced inhibition was not significantly changed in
      either condition. Baclofen action was also not affected by the adenylate cyclase
      inhibitor SQ 22536 or the protein kinase C inhibitor chelerythrine chloride.
      Baclofen still reduced mIPSC frequency in the presence of the polyvalent cation
      ruthenium red, which acts as a secretagogue here; however, baclofen-induced
      inhibition was reduced significantly. Furthermore, baclofen produced no clear
      inhibition during high-frequency mIPSCs bursts induced by the potent secretagogue
      alpha-Latrotoxin. Together, these results suggest that GABA(B) inhibition occurs
      downstream of Ca(2+) influx and may be mediated, in part, by an inhibition of the
      vesicular release mechanism.

PMID- 15255980
TI  - Neurotrophins induce short-term and long-term changes of cortical neurotrophin
      expression.
AB  - Neuronal activity, hormones, transmitters, physical exercise and enrichment
      influence cortical neurotrophin expression. Neurotrophins then elicit structural
      and physiological changes, and regulate gene expression. This prompted the
      hypothesis that neurotrophins themselves are involved in regulating neurotrophin
      expression. Here we investigated the mRNA expression level of brain-derived
      neurotrophic factor (BDNF), neurotrophin-4 (NT-4), NT-3 and nerve growth factor
      (NGF) as well as the tyrosine receptor kinases TrkB and TrkC receptor in response
      to BDNF, NT-4, NT-3 and NGF pulses in organotypic cortex cultures. Single
      neurotrophin pulses evoked a dramatic up- or down-regulation of some, but not all
      four, neurotrophin mRNAs, even within 3-24 h, indicating an immediate impact on
      neurotrophin transcription. Most strikingly, neurotrophin pulses during the first
      10 days in vitro (DIV) potentiated the expression of some neurotrophin mRNAs at
      20 DIV, suggesting that early trophic factor experience influences the expression
      levels seen later in development. The NT-3 mRNA expression, for example, was
      consistently promoted by NGF and BDNF, suggesting that these two factors help to
      maintain the low level of NT-3 found in adult cortex. Rapid bidirectional changes
      characterized the NT-4 mRNA expression. A single pulse of NT-4 transiently
      increased NT-4 mRNA, whereas a BDNF pulse transiently reduced NT-4 mRNA.
      Surprisingly, NGF strongly potentiated BDNF mRNA and in particular NT-4 mRNA. By
      contrast, TrkB mRNA remained constant at ages or time points at which other mRNAs
      amplified from the very same cDNA libraries revealed dramatic increases or
      decreases. Our study suggests the existence of a complex regulatory neurotrophin
      network controlling the expression of other neurotrophins.

PMID- 15255981
TI  - Brain-derived neurotrophic factor acutely depresses excitatory synaptic
      transmission to GABAergic neurons in visual cortical slices.
AB  - Brain-derived neurotrophic factor (BDNF) acutely modulates synaptic transmission
      to excitatory neurons in hippocampus and neocortex. The question of whether BDNF
      acts similarly on excitatory synaptic transmission to GABAergic neurons was
      eluded in previous studies using cortical slices. To address this question, we
      used transgenic mice in which expression of green fluorescence protein (GFP) is
      regulated by glutamic acid decarboxylase 67 (GAD67) promoter. In cortical slices
      prepared from these GAD67-GFP knock-in mice, we could detect GABAergic neurons
      under a fluorescent microscope. An application of BDNF rapidly depressed
      excitatory postsynaptic currents (EPSCs) evoked by layer IV stimulation in most
      GFP-positive neurons in layer II/III of the cortex. This effect was seen at
      synapses activated during the BDNF application and blocked by anti-TrkB IgG,
      indicating that the acute inhibitory action of BDNF is activity-dependent and
      mediated through TrkB. Paired-pulse ratios of the amplitude of EPSCs to paired
      stimulation at intervals of 10-100 ms were not significantly changed after BDNF
      application, suggesting that the site of depression may be postsynaptic.
      Responses to directly applied glutamate were also depressed by BDNF in most of
      neurons, being consistent with the interpretation of postsynaptic action of BDNF.
      The depressive action of BDNF was blocked by an intracellular injection of a
      Ca(2+) chelator, suggesting that a rise in Ca(2+) is involved in the acute
      depression of EPSCs. This action of BDNF was seen in 67% of parvalbumin (PV)
      positive neurons, but in only 19% of PV-negative neurons, indicating that the
      depressive action is biased to PV-positive GABAergic neurons.

PMID- 15255982
TI  - Blockade of presynaptic adenosine A1 receptor responses by nitric oxide and
      superoxide in rat hippocampus.
AB  - Activation of N-methyl-D-aspartate (NMDA) receptors prevents the neuronal
      responses to adenosine in hippocampal slices. As NMDA receptor activation leads
      to the generation of nitric oxide (NO) and superoxide, we have examined whether
      these can modify neuronal responses to adenosine and mediate the actions of NMDA.
      Field excitatory postsynaptic potentials were recorded in the CA1 region of rat
      hippocampal slices. Paired-pulse interactions were studied to localize the
      observed interactions to presynaptic terminals. The NO donors S-nitroso-N
      acetylpenicillamine and diethylamine NONOate induced a long-lasting potentiation
      (NO-induced potentiation) of field excitatory postsynaptic potential slope and
      significantly prevented the presynaptic inhibitory effect of adenosine or the A1
      receptor agonist N6-cyclopentyladenosine selectively with no effect on responses
      to baclofen. The superoxide-generating system of xanthine/xanthine oxidase also
      prevented presynaptic responses to adenosine and this effect was prevented by
      superoxide dismutase (SOD). The guanylate cyclase inhibitor 1H-[1,2,4]
      oxadiazolo[4,3a]quinoxalin-1-one (10 microM) prevented NO-induced potentiation
      and the inhibitory effects of S-nitroso-N-acetylpenicillamine and
      xanthine/xanthine oxidase on adenosine responses. The inhibitory effect of NMDA
      on adenosine responses was unchanged by 1H-[1,2,4]-oxadiazolo[4,3a]quinoxalin-1
      one, indicating that guanosine-3',5-cyclic monophosphate does not mediate this
      interaction, although it was partially reduced by SOD, suggesting that superoxide
      might contribute. The reduction of adenosine responses by electrically-induced
      long-term potentiation was prevented by NO synthase inhibition or SOD. The
      results indicate that the presynaptic effects of adenosine at presynaptic sites
      can be prevented by NO or superoxide but that neither of these individually can
      fully account for the prevention of adenosine responses by NMDA.

PMID- 15255983
TI  - Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells.
AB  - The ability of cells to generate an appropriate spike output depends on a balance
      between membrane depolarizations and the repolarizing actions of K(+) currents.
      The high-voltage-activated Kv3 class of K(+) channels repolarizes Na(+) spikes to
      maintain high frequencies of discharge. However, little is known of the ability
      for these K(+) channels to shape Ca(2+) spike discharge or their ability to
      regulate Ca(2+) spike-dependent burst output. Here we identify the role of Kv3
      K(+) channels in the regulation of Na(+) and Ca(2+) spike discharge, as well as
      burst output, using somatic and dendritic recordings in rat cerebellar Purkinje
      cells. Kv3 currents pharmacologically isolated in outside-out somatic membrane
      patches accounted for approximately 40% of the total K(+) current, were very fast
      and high voltage activating, and required more than 1 s to fully inactivate. Kv3
      currents were differentiated from other tetraethylammonium-sensitive currents to
      establish their role in Purkinje cells under physiological conditions with
      current-clamp recordings. Dual somatic-dendritic recordings indicated that Kv3
      channels repolarize Na(+) and Ca(2+) spikes, enabling high-frequency discharge
      for both types of cell output. We further show that during burst output Kv3
      channels act together with large-conductance Ca(2+)-activated K(+) channels to
      ensure an effective coupling between Ca(2+) and Na(+) spike discharge by
      preventing Na(+) spike inactivation. By contributing significantly to the
      repolarization of Na(+) and especially Ca(2+) spikes, our data reveal a novel
      function for Kv3 K(+) channels in the maintenance of high-frequency burst output
      for cerebellar Purkinje cells.

PMID- 15255984
TI  - Functional topology of the mossy fibre-granule cell--Purkinje cell system
      revealed by imaging of intrinsic fluorescence in mouse cerebellum.
AB  - We report an activity-induced green fluorescence signal observed when mouse
      cerebellar slices were illuminated with blue light and parallel fibre-Purkinje
      cell synapses were activated. The optical signal consisted of an initial increase
      in fluorescence that peaked within 1-2 s after the onset of stimulation, followed
      by a long lasting (40 s) transient decrease in fluorescence. Single or tetanic
      electrical stimuli applied to the molecular layer elicited 'beam-shaped'
      fluorescence changes along the trajectory of parallel fibres. These signals
      reported activation of Purkinje cells as they were depressed by antagonists of
      ionotropic and metabotropic glutamate receptors at Purkinje cells and correlated
      with Purkinje cell spiking activity. Optical responses induced by direct
      pharmacological activation of glutamate receptors were reduced by a calcium-free
      extracellular medium, consistent with the hypothesis that they reflect metabolic
      activity due to an increased intracellular calcium load associated with neuronal
      activation. We used these intrinsic fluorescence signals to address the question
      of whether granule cells excite Purkinje cells only locally via the ascending
      branches of their axons, or more widespread along the parallel fibre trajectory.
      White matter stimulation of the mossy fibres also elicited a beam-like
      fluorescence change along the trajectory of parallel fibres. Simultaneous imaging
      and extracellular recording demonstrated the association between the beam-like
      fluorescence signal and Purkinje cell spiking. This non-invasive imaging
      technique supports the notion that parallel fibre activity, evoked either locally
      or through the mossy fibre-granule cell pathway, can activate postsynaptic
      Purkinje cells along more than 3 mm of the parallel fibre trajectory.

PMID- 15255985
TI  - In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine
      concentration without alterations in mitochondrial function in the prefrontal
      cortex of medicated schizophrenic patients at rest.
AB  - The (31)P NMR localised method was used to study the metabolism of phospholipid
      and high energy phosphate in the prefrontal cortex. The spectra were taken from
      patients with schizophrenia (11 males) receiving neuroleptic medication, and were
      compared to normal controls (15 males). Their spectral intensities were analysed
      using a non-linear least-squares method with a prior knowledge of the fixed
      chemical shifts and linewidths, leading to further resolution into resonances of
      glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC),
      phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite
      concentrations were calculated referring to the spectral intensities of phosphate
      phantoms with known concentrations. T1 values of phantom and cerebrum were
      estimated from a series of localised inversion recovery spectra to correct for
      the signal saturation effects. The schizophrenic patients showed an increased
      concentration of GPC but not GPE, PE or PC. Furthermore, no difference was
      observed regarding the concentration of high-energy phosphates such as
      phosphocreatine, inorganic phosphate and ATP. The patients did not show any
      differences in mitochondrial function such as phosphorylation potential and the
      ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the
      prefrontal cortex could be characteristic of the pathophysiology of schizophrenia
      with mild negative symptoms.

PMID- 15255986
TI  - Subcortical visual system of the African mole-rat Cryptomys anselli: to see or
      not to see?
AB  - Abstract We studied the retinal projections, the distribution of cytochrome
      oxidase activity and the cyto- and myeloarchitecture of the subcortical visual
      system in the subterranean Ansell's mole-rat Cryptomys anselli. The optic nerve
      contained 1500 myelinated and a similar number of unmyelinated fibres. The retina
      projected to all the visual structures described in surface-dwelling sighted
      rodents. The suprachiasmatic nucleus was large and received bilateral retinal
      input. All other visual nuclei were reduced in size, were cytoarchitecturally
      poorly developed and received almost exclusively contralateral retinal
      projections. The dorsal and ventral lateral geniculate nuclei were moderately
      reduced and heavily innervated. The intergeniculate leaflet could be identified
      between these two nuclei. Pretectal nuclei were also relatively well-developed.
      The nucleus of the optic tract, the olivary pretectal nucleus, and the anterior
      and posterior pretectal nuclei were innervated by the retina. By contrast, the
      superficial, retinorecipient layers of the superior colliculus showed extreme
      reduction. The strata zonale, griseum superficiale and opticum were collapsed to
      a single layer 40 micro m thick. The accessory optic system was vestigial. These
      findings indicate that the functional subsystems involved in photoperiod
      perception, form and brightness discrimination, and movement analysis are
      anatomically rather well developed, whereas those involved in coordination of
      visuomotor reflexes are severely reduced. Thus, the visual system of C. anselli
      is much better developed than that of the blind mole-rat Spalax ehrenbergi. We
      suggest that Cryptomys anselli has retained basic visual capabilities.

PMID- 15255987
TI  - Time-dependent changes in the expression of the MEF2 transcription factor family
      during topographic map reorganization in mammalian visual cortex.
AB  - Removal of retinal input from a restricted region of adult mammalian visual
      cortex leads to a substantial reorganization of the retinotopy within the lesion
      projection zone (LPZ) of primary visual cortex (area 17). Little is known about
      the molecular mechanisms underlying such cortical plasticity. We investigated
      whether small but homonymous central retinal lesions induced differences in gene
      expression patterns between central area 17, the LPZ, vs. peripheral area 17 of
      the adult cat. Systematic differential mRNA display screening revealed higher
      levels for the mRNA encoding the transcription factor MEF2A in the LPZ. Semi
      quantitative PCR confirmed this dependency of mef2A mRNA expression on visual
      eccentricity in area 17 of animals with retinal lesions in contrast to normal
      animals. Western blotting experiments extended these data to the protein level
      and to two other members of the MEF2 transcription factor family, i.e. MEF2C and
      MEF2D. Quantitative analysis of the Western blotting experiments further revealed
      a post-lesion survival time-dependent change in expression for all three MEF2
      family members. The lesion effect was maximal at 3 days and 1 month post-lesion,
      but only minor at 2 weeks post-lesion. Interestingly, complete removal of retinal
      input from area 17 by surgery did not significantly alter the expression of the
      MEF2 transcription factors, excluding a definite correlation between neuronal
      activity and MEF2A expression levels. MEF2A immunocytochemistry confirmed both
      qualitatively and quantitatively the Western blotting observations in all animal
      models. Together, our findings identified a brain plasticity-related expression
      pattern for the MEF2 transcription factor family in adult mammalian neocortex.

PMID- 15255988
TI  - Resistance to extinction is associated with impaired immediate early gene
      induction in medial prefrontal cortex and amygdala.
AB  - Extinction of classical fear conditioning is thought to involve activity
      dependent potentiation of synaptic transmission in the medial prefrontal cortex
      (mPFC), resulting in the inhibition of amygdala-dependent fear responses. While
      many studies have addressed the mechanisms underlying extinction learning, it is
      unclear what determines whether extinction memory is consolidated or whether
      spontaneous recovery of the fear response occurs. Here we show, using a combined
      electrophysiological and immunocytochemical approach, that spontaneous recovery
      of conditioned fear in mice is associated with a prolonged expression of long
      term depression of synaptic transmission in the mPFC and the failure of induction
      of the immediate-early genesc-Fos and zif268 in the mPFC and the basolateral
      nucleus of the amygdala. This suggests that coordinated activity-dependent
      changes in gene expression in the mPFC and the amygdala may underlie the
      formation of long-term fear extinction memory.

PMID- 15255989
TI  - Reward expectation, orientation of attention and locus coeruleus-medial frontal
      cortex interplay during learning.
AB  - Regulation of attention and promotion of behavioural flexibility are functions
      attributed to both the noradrenergic nucleus locus coeruleus (LC) and the
      prefrontal cortex (PFC). The PFC receives a large innervation from LC and small
      changes in catecholaminergic activity in PFC profoundly affect cognitive
      function. It is crucial to the understanding of learning-related plasticity, that
      the cognitive context driving LC neurons be determined and the relation to
      activity in PFC be elucidated. To this end simultaneous recordings were made from
      LC and prelimbic cortex (PL) during an odour-reward association task in the rat.
      Neuronal activity related to orientation of attention, reward predictability,
      reward itself, and changes in stimulus reinforcement contingencies, was measured.
      All LC neurons and a significant proportion of PL neurons were engaged during
      several aspects of a Go/NoGo task, especially after the signal for trial onset
      and CS+ presentation. LC activation was, however, more tightly aligned to the
      behavioural response than to the CS+ 22% of PL neurons were activated during the
      response-reward delay. This suggests that the activity of both these structures
      is related to reward anticipation. Finally, LC neurons exhibited rapid plasticity
      when the reward-contingency was modified. Within-trial response latencies were
      always shorter in LC than in PL and between-trial response adaptation in LC
      preceded that in PL by many trials. Identifying such temporal relationships is an
      essential step toward understanding how neuromodulatory inputs to forebrain
      networks might promote or permit experience-dependent plasticity in behavioural
      situations.

PMID- 15255990
TI  - Decreased histamine H1 receptor binding in the brain of depressed patients.
AB  - The central histaminergic neuron system modulates the wakefulness, sleep-awake
      cycle, appetite control, learning and memory, and emotion. Previous studies have
      reported changes in neuronal histamine release and its metabolism under stress
      conditions in the mammalian brain. In this study, we examined, using positron
      emission tomography (PET) and [(11)C]-doxepin, whether the histaminergic neuron
      system is involved in human depression. Cerebral histamine H1 receptor (H(1)R)
      binding was measured in 10 patients with major depression and in 10 normal age
      matched subjects using PET and [(11)C]-doxepin. Data were calculated by a
      graphical analysis on voxel-by-voxel and ROI (region of interests) basis. Binding
      potential (BP) values for [(11)C]-doxepin binding in the frontal and prefrontal
      cortices, and cingulate gyrus were significantly lower in the depressed patients
      than those in the normal control subjects. There was no area of the brain where
      [(11)C]-doxepin binding was significantly higher in the depressed patients than
      in the controls. ROI-based analysis also revealed that BP values for [(11)C]
      doxepin binding in the frontal cortex and cingulate gyrus decreased in proportion
      to self-rating depressive scales scores. The results of this study demonstrate
      that depressed patients have decreased brain H(1)R binding and that this decrease
      correlates with the severity of depression symptoms. It is therefore suggested
      that the histaminergic neuron system plays an important role in the
      pathophysiology of depression and that its modulation may prove to be useful in
      the treatment of depression.

PMID- 15255991
TI  - Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis.
AB  - A prominent hallmark of Alzheimer's disease pathology is cerebral amyloidosis.
      However, it is not clear how extracellular amyloid-beta peptide (A beta)
      deposition and amyloid formation compromise brain function and lead to dementia.
      It has been argued that extracellular amyloid deposition is neurotoxic and/or
      that soluble A beta oligomers impair synaptic function. Amyloid deposits, by
      contrast, may affect diffusion properties of the brain interstitium with
      implications for the transport of endogenous signalling molecules during synaptic
      and/or extrasynaptic transmission. We have used diffusion-weighted magnetic
      resonance imaging to study diffusion properties in brains of young (6-month-old)
      and aged (25-month-old) APP23 transgenic mice and control littermates. Our
      results demonstrate that fibrillar amyloid deposits and associated gliosis in
      brains of aged APP23 transgenic mice are accompanied by a reduction in the
      apparent diffusion coefficient. This decrease was most pronounced in neocortical
      areas with a high percentage of congophilic amyloid and was not significant in
      the caudate putamen, an area with only modest and diffuse amyloid deposition.
      These findings suggest that extracellular deposition of fibrillar amyloid and/or
      associated glial proliferation and hypertrophy cause restrictions to interstitial
      fluid diffusion. Reduced diffusivity within the interstitial space may alter
      volume transmission and therefore contribute to the cognitive impairment in
      Alzheimer's disease.

PMID- 15255992
TI  - Latent inhibition of cued fear conditioning: an NMDA receptor-dependent process
      that can be established in the presence of anisomycin.
AB  - Much of the research examining the biological basis for long-term memories has
      focused on mechanisms that support the formation of conditioned associations.
      Less information is available on biological mechanisms which underlie processes
      that modify the strength of conditioned associations. Latent inhibition is a
      phenomenon by which pre-exposure to a to-be-conditioned stimulus (CS) weakens
      subsequent conditioning of that CS to an unconditioned stimulus (US). Here we
      report that latent inhibition of cued fear conditioning is dependent on NMDA
      receptor activation. MK-801 (1 mg/kg), an NMDA receptor antagonist, abolished
      latent inhibition of cued fear conditioning. This dose of MK-801 administered
      before training did not disrupt cued fear conditioning. Conversely, anisomycin
      (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of
      cued fear conditioning when administered 20 min before, immediately after, or 2,
      4, 6, or 8 h after CS pre-exposure. Furthermore, continuous anisomycin
      administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to
      pre-exposure) did not disrupt latent inhibition of cued fear conditioning. In
      addition, anisomycin had no effect on a long-lasting version of latent inhibition
      of cued fear conditioning that was maintained over a 7-day interval. Anisomycin
      administered before training, however, disrupted learning of the CS-US
      association. These findings suggest that latent inhibition of cued fear
      conditioning is a long-lasting NMDA receptor-dependent process that can develop
      during the inhibition of protein synthesis.

PMID- 15255993
TI  - Transfer of adaptation from visually guided saccades to averaging saccades
      elicited by double visual targets.
AB  - The adaptive mechanisms that control the amplitude of visually guided saccades
      (VGS) are only partially elucidated. In this study, we investigated, in six human
      subjects, the transfer of VGS adaptation to averaging saccades elicited by the
      simultaneous presentation of two visual targets. The generation of averaging
      saccades requires the transformation of two representations encoding the desired
      eye displacement toward each of the two targets into a single representation
      encoding the averaging saccade (averaging programming site). We aimed to evaluate
      whether VGS adaptation acts upstream (hypothesis 1) or at/below (hypothesis 2)
      the level of averaging saccades programming. Using the double-step target
      paradigm, we simultaneously induced a backward adaptation of 17.5 degrees
      horizontal VGS and a forward adaptation of 17.5 degrees oblique VGS performed
      along the +/- 40 degrees directions relative to the azimuth. We measured the
      effects of this dual adaptation protocol on averaging saccades triggered by two
      simultaneous targets located at 17.5 degrees along the +/- 40 degrees directions.
      To increase the yield of averaging saccades, we instructed the subjects to move
      their eyes as fast as possible to an intermediate position between the two
      targets. We found that the amplitude of averaging saccades was smaller after VGS
      adaptation than before and differed significantly from that predicted by
      hypothesis 1, but not by hypothesis 2, with an adaptation transfer of 50%. These
      findings indicate that VGS adaptation largely occurs at/below the averaging
      saccade programming site. Based on current knowledge of the neural substrate of
      averaging saccades, we suggest that VGS adaptation mainly acts at the level of
      the superior colliculus or downstream.

PMID- 15255994
TI  - Reduced ocular dominance plasticity and long-term potentiation in the developing
      visual cortex of protein kinase A RII alpha mutant mice.
AB  - The cAMP-dependent protein kinase (PKA) signalling pathway has been shown to play
      an important role in long-term potentiation (LTP) and depression (LTD), and
      ocular dominance plasticity in the visual cortex. In order to investigate further
      the involvement of individual PKA subunits in visual cortical plasticity, LTP and
      LTD in vitro and ocular dominance plasticity in vivo in the developing visual
      cortex were examined in mice lacking the RII alpha subunit of PKA. Here we show
      that LTP in layers II/III was decreased in RII alpha knockout mice, but LTD was
      almost unaffected, and the ocular dominance shift induced by monocular
      deprivation was also partially blocked. These data provide evidence that RII
      alpha is involved in LTP and ocular dominance plasticity, and further suggest
      that different afferent inputs could selectively activate particular subunits of
      PKA and thereby direct specific aspects of visual cortical plasticity.

PMID- 15255995
TI  - Brain-derived neurotrophic factor is expressed in a gradient in the superior
      colliculus during development of the retinocollicular projection.
AB  - Abstract Theoretical models of topographic map formation have postulated a
      gradient of attractant in addition to a gradient of repulsion in the target. In
      species where many axons grow past their correct positions initially, it has also
      been argued that a parallel gradient of attractant or branching signal is
      required to ensure collateral formation at the correct position (O'Leary et al.,
      1999). Brain-derived neurotrophic factor (BDNF) is a known attractant and
      promotes branching of retinal axons. We have examined its distribution in the
      superior colliculus and that of its receptor, trkB, in the retina, using
      immunohistochemistry and in situ hybridization, respectively, during the
      development of the topographic retinocollicular projection in the wallaby, a
      marsupial mammal. The number of glial endfeet expressing BDNF at the surface of
      the colliculus was found to be in a high caudal-to-low rostral gradient during
      the time when the retinocollicular projection was developing. When the projection
      was mature the rostrocaudal gradient had disappeared and the number of detectable
      endfeet expressing BDNF was very low. Messenger RNA for TrkB was expressed in the
      retinal ganglion cell layer throughout the time when the retinocollicular
      projection was developing, with no difference in expression across the
      nasotemporal axis of the retina. The low rostral to high caudal distribution of
      BDNF in glial endfeet supports the idea that it is providing a parallel gradient
      of attractant or branching signal in the colliculus.

PMID- 15255996
TI  - Evidence for differential modulation of conditioned aversion and fear-conditioned
      analgesia by CB1 receptors.
AB  - Fear-conditioned analgesia is an important survival response mediated by
      substrates controlling nociception and aversion. Cannabinoid(1) (CB(1)) receptors
      play an important role in nociception and aversion. However, their role in fear
      conditioned analgesia has not been investigated. This study investigated the
      effects of systemic administration of the CB(1) receptor antagonist, SR141716A (1
      mg/kg, i.p.), on fear-conditioned analgesia and conditioned aversion in rats.
      Twenty-four hours after receiving footshock, rats exhibited reduced formalin
      evoked nociceptive behaviour, increased freezing and increased defecation when
      tested in the footshock apparatus, compared with non-footshocked formalin
      injected rats. SR141716A attenuated fear-conditioned analgesia, freezing and
      defecation. Importantly, SR141716A had no effect on formalin-evoked nociceptive
      behaviour over an equivalent time period in rats not receiving footshock.
      SR141716A had no effect on contextually induced freezing during the first half of
      the test trial in rats receiving intra-plantar injection of saline.
      Administration of SR1417176A did, however, attenuate short-term extinction of
      contextually induced freezing and ultrasound emission in rats receiving intra
      plantar saline, compared with vehicle-treated saline controls. These data suggest
      an important role for the CB(1) receptor in mediating fear-conditioned analgesia
      and provide evidence for differential modulation of conditioned aversive
      behaviour by CB(1) receptors during tonic, persistent pain.

PMID- 15255997
TI  - The rewarding properties of MDMA are preserved in mice lacking mu-opioid
      receptors.
AB  - The involvement of mu-opioid receptors in the rewarding properties of MDMA was
      explored in mu-opioid receptor knockout mice using the conditioning place
      preference paradigm. The associated release of dopamine in the nucleus accumbens
      was investigated by in vivo microdialysis. A significant rewarding effect of MDMA
      (10 mg/kg, i.p.) was observed in both wild-type and mu-opioid receptor knockout
      mice. MDMA (10 mg/kg, i.p.) also induced similar increases in dopamine and
      decreases in 3,4-dihydroxyphenylacetic acid and homovanillic acid in the nucleus
      accumbens dialysates of both wild-type and mu-opioid receptor knockout mice. No
      significant differences in basal levels of dopamine, 3,4-dihydroxyphenylacetic or
      homovanillic acids between wild-type and mu-opioid receptor knockout mice were
      observed. In summary, the present results suggest that, in contrast to what has
      been reported for other drugs of abuse such as opioids, ethanol, nicotine and
      Delta(9)-tetrahydrocannabinol, mu-opioid receptors do not play a major role in
      the rewarding properties of MDMA. These differences could be due to distinct
      mechanisms controlling dopamine release in the nucleus accumbens and suggest that
      the effects of MDMA on dopaminergic neurons are independent of micro -opioid
      receptors.

PMID- 15255998
TI  - Prolonged cannabinoid treatment results in spatial working memory deficits and
      impaired long-term potentiation in the CA1 region of the hippocampus in vivo.
AB  - Adult male Long-Evans rats were administered the potent cannabinoid 1 receptor
      agonist HU-210 (100 microg/kg, i.p.) for 15 days continuously and their
      performance on a matching-to-place version of the Morris water maze was
      subsequently evaluated. Overall, experimental animals performed significantly
      worse initially on the reference memory component of this task, but their
      performance improved over 5 days until it was indistinguishable from that of
      control animals. Animals given HU-210 did not exhibit working memory impairments
      at short intertrial delays (30 s); however, significant impairments were observed
      in learning performance with longer intertrial delays (300 s). In vivo
      electrophysiological analyses revealed that long-term potentiation in the CA1
      region of the hippocampus was significantly impaired following the administration
      of HU-210 for 15 days. These results indicate that long-term cannabinoid exposure
      can produce marked deficits in reference and working memory performance, and also
      impair hippocampal synaptic plasticity in vivo.

PMID- 15256000
TI  - Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin
      resistance in Enterobacteriaceae.
AB  - Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be
      difficult to detect using standard methods of either Kirby-Bauer disc diffusion
      (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This
      difficulty is due to genetic differences in resistance determinants, differences
      in levels of gene expression, and variation in spectra of enzymatic activity
      against the substrate beta-lactams used for susceptibility testing. We have
      examined 95 clinical isolates reportedly susceptible to ceftazidime and
      ceftriaxone, as originally determined by either KBDD or MIC methods. The
      organisms studied here were isolated in 2002 from two pediatric hospital centers
      (Seattle, USA and Shanghai, China). They belong to the inducible beta-lactamase
      producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp.,
      Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby
      Bauer disc approximation (KBDA) method identified inducible phenotypes of third
      generation cephalosporin resistance in 76% of isolates, which would otherwise be
      considered susceptible by standard KBDD methods.

PMID- 15256001
TI  - Coffee bean extracts rich and poor in kahweol both give rise to elevation of
      liver enzymes in healthy volunteers.
AB  - BACKGROUND: Coffee oil potently raises serum cholesterol levels in humans. The
      diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil
      also causes elevation of liver enzyme levels in serum. It has been suggested that
      cafestol is mainly responsible for the effect on serum cholesterol levels and
      that kahweol is mainly responsible for the effect on liver enzyme levels. The
      objective of this study was to investigate whether coffee oil that only contains
      a minute amount of kahweol indeed does not cause elevation of liver enzyme
      levels. METHODS: The response of serum alanine aminotransferase (ALAT) and
      aspartate aminotransferase (ASAT) to Robusta coffee oil (62 mg/day cafestol, 1.6
      mg/day kahweol) was measured in 18 healthy volunteers. RESULTS: After nine days
      one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times
      the upper limit of normal (ULN). Another two subjects stopped treatment due to
      other reasons. After 16 days another two subjects were taken off Robusta oil
      treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for
      ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7
      ULN. It was then decided to terminate the study. The median response of subjects
      to Robusta oil after 16 days was 0.27 ULN (n = 15, 25th,75th percentile:
      0.09;0.53) for ALAT and 0.06 ULN (25th,75th percentile -0.06;0.22) for ASAT.
      CONCLUSIONS: We conclude that the effect on liver enzyme levels of coffee oil
      containing hardly any kahweol is similar to that of coffee oil containing high
      amounts of kahweol. Therefore it is unlikely that kahweol is the component of
      coffee oil that is responsible for the effect. Furthermore, we conclude that
      otherwise unexplained elevation of liver enzyme levels observed in patients might
      be caused by a switch from consumption of filtered coffee to unfiltered coffee.

PMID- 15255999
TI  - Molecular profiling of malignant peripheral nerve sheath tumors associated with
      neurofibromatosis type 1, based on large-scale real-time RT-PCR.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with
      a complex range of clinical symptoms. The hallmark of NF1 is the onset of
      heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas
      can give rise to malignant peripheral nerve sheath tumors (MPNSTs), and the
      underlying molecular mechanisms are largely unknown. RESULTS: To obtain further
      insight into the molecular pathogenesis of MPNSTs, we used real-time quantitative
      RT-PCR to quantify the mRNA expression of 489 selected genes in MPNSTs, in
      comparison with plexiform neurofibromas. The expression of 28 (5.7%) of the 489
      genes was significantly different between MPNSTs and plexiform neurofibromas; 16
      genes were upregulated and 12 were downregulated in MPNSTs. The altered genes
      were mainly involved in cell proliferation (MKI67, TOP2A, CCNE2), senescence
      (TERT, TERC), apoptosis (BIRC5/Survivin, TP73) and extracellular matrix
      remodeling (MMP13, MMP9, TIMP4, ITGB4). More interestingly, other genes were
      involved in the Ras signaling pathway (RASSF2, HMMR/RHAMM) and the Hedgehog-Gli
      signaling pathway (DHH, PTCH2). Several of the down-regulated genes were Schwann
      cell-specific (L1CAM, MPZ, S100B, SOX10, ERBB3) or mast cell-specific (CMA1,
      TPSB), pointing to a depletion and/or dedifferentiation of Schwann cells and mast
      cells during malignant transformation of plexiform neurofibromas. CONCLUSION:
      These data suggest that a limited number of signaling pathways, and particularly
      the Hedgehog-Gli signaling pathway, may be involved in malignant transformation
      of plexiform neurofibromas. Some of the relevant genes or their products warrant
      further investigation as potential therapeutic targets in NF1.

PMID- 15256002
TI  - The influence of tumor size and environment on gene expression in commonly used
      human tumor lines.
AB  - BACKGROUND: The expression profiles of solid tumor models in rodents have been
      only minimally studied despite their extensive use to develop anticancer agents.
      We have applied RNA expression profiling using Affymetrix U95A GeneChips to
      address fundamental biological questions about human tumor lines. METHODS: To
      determine whether gene expression changed significantly as a tumor increased in
      size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT
      116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate
      whether gene expression was influenced by the strain of mouse, tumor samples
      isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene
      expression differences between tissue culture and in vivo samples were
      investigated by comparing profiles from lines grown in both environments.
      RESULTS: Multidimensional scaling and analysis of variance demonstrated that the
      tumor lines were dramatically different from each other and that gene expression
      remained constant as the tumors increased in size. Statistical analysis revealed
      that 63 genes were differentially expressed due to the strain of mouse the tumor
      was grown in but the function of the encoded proteins did not link to any
      distinct biological pathways. Hierarchical clustering of tissue culture and
      xenograft samples demonstrated that for each individual tumor line, the in vivo
      and in vitro profiles were more similar to each other than any other profile. We
      identified 36 genes with a pattern of high expression in xenograft samples that
      encoded proteins involved in extracellular matrix, cell surface receptors and
      transcription factors. An additional 17 genes were identified with a pattern of
      high expression in tissue culture samples and encoded proteins involved in cell
      division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor
      line is grown in can have a significant effect on gene expression but tumor size
      has little or no effect for subcutaneously grown solid tumors. Furthermore, an
      individual tumor line has an RNA expression pattern that clearly defines it from
      other lines even when grown in different environments. This could be used as a
      quality control tool for preclinical oncology studies.

PMID- 15256003
TI  - Activation of cytokines and NF-kappa B in corneal epithelial cells infected by
      respiratory syncytial virus: potential relevance in ocular inflammation and
      respiratory infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower
      respiratory tract infection, claiming millions of lives annually. The virus
      infects various cells of the respiratory tract as well as resident inflammatory
      cells such as macrophages. Infection activates a variety of cellular factors such
      as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of
      which are important players in the respiratory disease. However, the exact
      natural route of RSV infection and its etiology remain relatively unknown. In
      this paper, we test the hypothesis that human corneal epithelial cells, which
      constitute the outermost layer of the cornea, can be infected with RSV, and that
      the infection leads to the activation of proinflammatory macromolecules. RESULTS:
      Corneal swabs obtained from pediatric patients with acute respiratory disease
      were found to contain RSV at a high frequency (43 positive out of 72 samples,
      i.e., 60%). Primary corneal epithelial cells in tissue culture supported robust
      infection and productive growth of RSV. Infection resulted in the activation of
      TNF-alpha, IL-6 and sixteen chemokines as well as NF-kappa B. Three
      proinflammatory CXC chemokines (MIG, I-TAC, IP-10) underwent the greatest
      activation. CONCLUSIONS: The ocular epithelium is readily infected by RSV. The
      pro-inflammatory cytokines are likely to play critical roles in the etiology of
      inflammation and conjunctivitis commonly seen in pediatric patients with
      respiratory infections. RSV-eye interactions have important implications in RSV
      transmission, immunopathology of RSV disease, and in the management of
      conjunctivitis.

PMID- 15256021
TI  - The structure of the cell wall peptidoglycan of Bacillus cereus RSVF1, a strain
      closely related to Bacillus anthracis.
AB  - The peptidoglycan of Bacillus cereus RSVF1, a close relative of Bacillus
      anthracis, has several distinguishing features: the overwhelming majority of
      cross-linked muropeptides are dimers, higher oligomers are only present in minute
      quantities; and virtually all muropeptides lack the N-acetyl group from
      glucosamine residues, thus explaining resistance of the cell walls to lysozyme.

PMID- 15256004
TI  - Formin homology 2 domains occur in multiple contexts in angiosperms.
AB  - BACKGROUND: Involvement of conservative molecular modules and cellular mechanisms
      in the widely diversified processes of eukaryotic cell morphogenesis leads to the
      intriguing question: how do similar proteins contribute to dissimilar
      morphogenetic outputs. Formins (FH2 proteins) play a central part in the control
      of actin organization and dynamics, providing a good example of evolutionarily
      versatile use of a conserved protein domain in the context of a variety of
      lineage-specific structural and signalling interactions. RESULTS: In order to
      identify possible plant-specific sequence features within the FH2 protein family,
      we performed a detailed analysis of angiosperm formin-related sequences available
      in public databases, with particular focus on the complete Arabidopsis genome and
      the nearly finished rice genome sequence. This has led to revision of the current
      annotation of half of the 22 Arabidopsis formin-related genes. Comparative
      analysis of the two plant genomes revealed a good conservation of the previously
      described two subfamilies of plant formins (Class I and Class II), as well as
      several subfamilies within them that appear to predate the separation of monocot
      and dicot plants. Moreover, a number of plant Class II formins share an
      additional conserved domain, related to the protein phosphatase/tensin/auxilin
      fold. However, considerable inter-species variability sets limits to
      generalization of any functional conclusions reached on a single species such as
      Arabidopsis. CONCLUSIONS: The plant-specific domain context of the conserved FH2
      domain, as well as plant-specific features of the domain itself, may reflect
      distinct functional requirements in plant cells. The variability of formin
      structures found in plants far exceeds that known from both fungi and metazoans,
      suggesting a possible contribution of FH2 proteins in the evolution of the plant
      type of multicellularity.

PMID- 15256022
TI  - Characterization and localization of drug resistance determinants in multidrug
      resistant, integron-carrying Salmonella enterica serotype Typhimurium strains.
AB  - The genetic background of the antimicrobial resistance of 10 selected
      multiresistant Salmonella serotype Typhimurium (S. Typhimurium) strains
      (including the emerging monophasic variant [4,5,12:i:- ]) was investigated. All
      strains shared class 1 integrons (with seven types of variable regions) and
      belonged to different lineages (L1-L6) according to their phage types, DNA
      polymorphisms by XbaI-pulsed-field gel electrophoresis (PFGE), integrons, and/or
      resistance patterns. The strains were screened for the presence and localization
      (chromosomal or plasmid) of 32 DNA sequences representing integron-, Tn21-like
      transposon-, resistance-, and virulence-plasmid genes. Strains belonging to
      lineage L1 (definitive phage type DT104) carried the 90-kb Salmonella virulence
      plasmid together with the complete or partial chromosomally located Salmonella
      Genomic Island 1 (SGI1). All strains belonging to the other five lineages carried
      their resistance determinants on various resistance plasmids. Two of these
      strains showed complex plasmid profiles, which included a 95 kb virulence plasmid
      together with two or four resistance plasmids. Two strains carried a resistance
      plasmid that lacked the virulence-plasmid-encoding sequences. The remaining two
      strains carried two different hybrid virulence-resistance plasmids. Twenty-three
      of the DNA sequences could be assigned to distinct XbaI genomic restriction
      patterns (PFGE profiles). In this way, the influence of the resistance and
      virulence plasmids on the PFGE profiles was determined, and several groups of
      resistance genes could be identified. The data obtained represent a useful
      epidemiological tool for tracing the emergence and distribution of multiresistant
      S. Typhimurium worldwide.

PMID- 15256023
TI  - Antibody-directed photodynamic therapy of methicillin resistant Staphylococcus
      aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a world-wide public health
      problem, causing nosocomial and community-acquired infections. Furthermore, MRSA
      is increasingly resistant to many conventional antimicrobials, so there is a real
      need to develop alternative approaches for MRSA decolonization and treatment.
      Previously, we have demonstrated that MRSA can be killed with an immunoglobulin G
      (IgG)-SnCe6 conjugate and red light, but effectiveness was dependent on the
      particular strain and the growth phase. In this investigation, we used an
      antibody raised against MRSA to make an Ab-SnCe6 conjugate capable of targeting
      many MRSA strains in all growth phases. To suspensions of important epidemic
      MRSA, each grown to stationary, lag, or exponential phase, the Ab-SnCe6 conjugate
      was added and samples exposed to red light. Survivors were then enumerated. This
      treatment was very effective at killing all the different MRSA strains tested, in
      all growth phases. The Ab-SnCe6 conjugate was able to kill EMRSA-16 selectively
      in a mixed suspension of EMRSA-16 and Escherichia coli, and was much better at
      killing EMRSA-16 than a coagulase-negative staphylococcus, S. epidermidis. These
      results demonstrate that photodynamic therapy of MRSA is very effective when the
      photosensitizer is targeted to the pathogen using a suitable antibody and may be
      a good candidate for a novel treatment of MRSA infections.

PMID- 15256024
TI  - Characterization of plasmid-mediated aphA-3 kanamycin resistance in Campylobacter
      jejuni.
AB  - A total of 254 isolates of Campylobacter jejuni and three isolates of
      Campylobacter coli, isolated from Sweden, Canada, and Egypt, were screened for
      kanamycin resistance. Eight strains of C. jejuni contained large plasmids that
      carried the aphA-3 kanamycin-resistance marker. In six plasmids, the aphA-3 gene
      was located downstream of an apparent insertion sequence, designated IS607*,
      which showed a considerable similarity to IS607, characterized on the chromosome
      of some Helicobacter pylori strains. In contrast, the other plasmids carried the
      aphA-3 gene as a part of a resistance cluster. This included three resistance
      markers encoding 6'-adenylyltransferase (aadE), streptothricin acetyltransferase
      (sat), and 3'-aminoglycoside phosphotransferase type III (aphA-3). The genetic
      organization of this resistance cluster suggests that it has been acquired by C.
      jejuni from a Gram-positive organism. The IS607* element was also observed in
      kanamycin-susceptible strains of C. jejuni on plasmids mediating tetracycline
      resistance. The kanamycin-resistance phenotype transferred along with
      tetracycline resistance by conjugation from four representative C. jejuni strains
      to a recipient strain of C. jejuni. The kanamycin-resistance determinant (aphA-3)
      was stably transferred from one of the four C. jejuni strains to a recipient
      strain of Escherichia coli. However, the C. jejuni plasmid, which also carries
      the tetO gene, was not maintained in E. coli. Pulsed-field gel electrophoresis
      revealed the integration of approximately 50 kb of the plasmid into the
      chromosome of the E. coli recipient.

PMID- 15256025
TI  - Clonal types and multidrug resistance patterns of methicillin-resistant
      Staphylococcus aureus (MRSA) recovered in Italy during the 1990s.
AB  - A large number (272) of methicillin-resistant Staphylococcus aureus (MRSA)
      isolates recovered from Italian hospitals during the early and late 1990s were
      characterized for multidrug resistance pattern and clonal type using a
      combination of genotyping methods, including pulsed-field gel electrophoresis
      (PFGE), spaA typing, multilocus sequence typing (MLST), determination of SCC mec
      type, and hybridization pattern with Tn 554. The majority of MRSA belonged to
      four genetic lineages: the pandemic Iberian and Brazilian clones, and two unique
      clonal types-the "Italian" and "Rome" clones of MRSA. The Italian clone carried
      the SCC mec type I in the genetic background of ST228, which is a double-locus
      variant of the sequence type of the multidrug-resistant New York/Japanese clone
      (ST5). The properties of the Rome clone showed several striking similarities to
      those of the Archaic clone of MRSA that was dominant among MRSA isolates in the
      mid-1960s to 1970s, but has not been detected since then in recent global
      surveillance studies.

PMID- 15256026
TI  - Vancomycin-resistant Enterococcus faecium isolates causing hospital outbreaks in
      northern Italy belong to the multilocus sequence typing C1 lineage.
AB  - Multilocus sequence typing (MLST) was used to obtain insights into the genetic
      relationships between 14 vancomycin-resistant Enterococcus faecium (VREF)
      isolates from humans (hospitalized patients, 5 strains) and nonhuman sources
      (meat and poultry, 9 strains) in northern Italy over the period 1993-2001. The
      typing scheme (Homan et al., 2002, J. Clin. Microb., 40:1963-1971) based on seven
      housekeeping genes--adk (adenylate kinase), atpA (ATP synthase, alpha subunit),
      ddl (D-alanine-D-alanine ligase), gyd (glyceraldehyde-3-phosphate dehydrogenase),
      gdh (glucose-6-phosphate dehydrogenase), purK (phosphoribosylaminoimidazole
      carboxylase ATPase subunit), and pstS (phosphate ATP-binding cassette
      transporter)--was used. In the 14 VREF analyzed, the number of unique alleles
      ranged from 1 (gyd) to 8 (atpA). Isolates from hospitalized patients were defined
      by the unique allele purK 1. Nine sequence types (STs) were identified. All of
      the epidemic strains isolated over the period 2000-2001 showed identical or
      closely related pulsed-field gel electrophoresis (PFGE) patterns and clustered in
      the same ST78. These strains shared six of the seven alleles with the strain CA20
      representative of the 1993-1999 outbreaks, which PFGE indicated as being
      unrelated to those of the recent outbreaks. MLST confirmed the unrelatedness of
      human and nonhuman strains already detected by PFGE. All isolates clustered in
      three main genetic lineages: group A comprised two of the three isolates from
      meat; group C the human strains of all outbreaks and one poultry strain; and
      group B four of the five poultry strains and one meat strain. All human strains
      carried the esp gene and clustered in the C1 sublineage that has been described
      as having emerged recently worldwide.

PMID- 15256027
TI  - Development of a standardized susceptibility test for campylobacter with quality
      control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and
      meropenem.
AB  - A standardized agar dilution susceptibility testing method was developed for
      Campylobacter that consisted of testing on Mueller-Hinton medium supplemented
      with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2.
      Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain.
      Minimal inhibitory concentration (MIC) QC ranges were determined for two
      incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C
      for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline,
      erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at
      both temperatures, 95-100% of the QC MIC results fell within recommended QC
      ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of
      Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C.
      lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni
      and C. coli could be reliably tested under both test conditions, growth of C.
      jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when
      incubated at 42 degrees C. Therefore, it is recommended that these species only
      be tested at 36 degrees C.

PMID- 15256028
TI  - Involvement of SHV-12 and SHV-2a encoding plasmids in outbreaks of extended
      spectrum beta-lactamase-producing Klebsiella pneumoniae in a Tunisian neonatal
      ward.
AB  - Previous genotypic investigations of extended-spectrum beta-lactamase (ESBL)
      producing Klebsiella pneumoniae recovered in a Tunisian neonatal ward revealed
      the spread of two epidemic strains and a high number of genetically unrelated
      isolates. The aim of the present study was to determine the role of the
      dissemination of self-transferrable plasmids harboring bla genes in the outbreaks
      experienced by the ward. The 49 previously identified clinical isolates of ESBL
      producing K. pneumoniae were examined for relationships between their enzymes and
      plasmids. Analysis of crude extracts by isoelectric focusing showed four beta
      lactamase-activities at pI 8.2, 7.6, 6, and 5.4. Clinical isolates contained
      large plasmids that could be transferred by conjugation and transformation
      conferring resistance to expanded-spectrum cephalosporins. DNA amplification and
      sequencing were performed to confirm the identities of transferred beta
      lactamases. Nucleotide sequence analysis of SHV-specific PCR products from six
      isolates identified two bla(SHV) genes corresponding to SHV derived ESBLs, SHV-12
      and SHV-2a. PstI digestion of plasmid DNA from transformants revealed six
      restriction patterns. The occurrence of the prevalent plasmid pattern in both
      epidemic strains and unrelated isolates indicated that diffusion and endemic
      persistence of the bla(SHV-ESBL) genes in the ward were due to concomitant spread
      of epidemic strains and plasmid dissemination among unrelated strains.

PMID- 15256029
TI  - Characterization of high-level aminoglycoside-resistant enterococci in Kuwait
      hospitals.
AB  - This study investigated the distribution of genes for aminoglycoside-modifying
      enzymes (AME) and the genetic relatedness of high-level aminoglycoside-resistant
      enterococci isolated in Kuwait hospitals. A total of 117 enterococci, consisting
      of 109 Enterococcus faecalis, seven Enterococcus faecium, and one Enterococcus
      casseliflavus were studied. The MICs of gentamicin, kanamycin, amikacin,
      tobramycin, and streptomycin were determined by agar dilution and the genes
      encoding the AAC(6')- APH(2"), ANT(4'), APH(3'), APH (2")-Ib, APH (2")-Ic, APH
      (2")-Id, and ANT(6) enzymes were amplified by PCR. They were typed by pulsed
      field gel electrophoresis (PFGE). Filter mating was used to transfer gentamicin
      resistance determinants. They were all resistant to kanamycin (MIC 2000 mg/L).
      Fifty-five isolates were resistant to gentamicin (MIC 500 mg/L), 72 were
      resistant to tobramycin (MIC 64 mg/L), 115 were resistant to amikacin (MIC 64
      mg/L), and 97 were resistant to streptomycin (MIC 1000 mg/L). The aac(6')-Ie
      aph(2")-Ia was detected in all isolates with gentamicin MIC 500 mg/L and in 15
      isolates with gentamicin MIC 256 mg/L. The aph(3')-IIIa gene was detected in 101
      isolates, whereas the ant(6')-Ia gene was detected in 85 of the 97 streptomycin
      resistant isolates with MIC 1000 mg/L. The aac(6')-Ii gene was detected only in
      the seven E. faecium isolates. None of them contained ant(4')-Ia, aph(2")-Ib,
      aph(2")-Ic and aph(2")-Id. PFGE revealed heterogeneous patterns with no dominant
      clone. The results demonstrated that AME are common in aminoglycoside-resistant
      enterococci isolated in Kuwait. However, the absence of a dominant clone suggests
      that they acquired high-level aminoglycoside independently.

PMID- 15256030
TI  - Reduced susceptibility to ciprofloxacin and gyra gene mutation in North Indian
      strains of Salmonella enterica serotype Typhi and serotype Paratyphi A.
AB  - The emergence of reduced susceptibility to ciprofloxacin among Salmonella
      enterica serotype Typhi and serotype Paratyphi A leading to clinical failure of
      treatment poses a great therapeutic challenge. The mechanism of fluoroquinolone
      resistance in clinical isolates of S. Typhi and S. Paratyphi A is not very well
      documented. The present study was carried out with the objective of molecular
      characterization of reduced quinolone susceptibility amongst the strains of S.
      Typhi and S. Paratyphi A isolated from the patients with enteric fever during
      January, 2000, to April, 2003, in a North Indian hospital. A total of 422 culture
      positive cases of enteric fever were reported to the hospital during the period
      of study, of which S. Typhi was isolated from 350 cases and S. Paratyphi A from
      72 cases. The antimicrobial susceptibility of these strains was determined by
      disk diffusion and agar dilution method according to NCCLS guidelines, and E-test
      method. A total of 140 randomly selected strains, isolated during the years 1993
      1999, that were available from the laboratory stocks were also studied to compare
      with the present strains. To study the quinolone susceptibility, the strains were
      divided into nalidixic acid sensitive (NAS), nalidixic acid intermediate
      resistant, (NAI) and nalidixic acid resistant (NAR) on the basis of
      susceptibility to nalidixic acid. Clinical history was available from 174
      patients, of which 93 needed hospitalization due to severe disease. Of these, 82
      patients were infected with NAR strains and 22 patients had a documented evidence
      of clinical failure to ciprofloxacin therapy. The patients infected with NAR
      strains were younger and had a significantly longer duration of fever (p value <
      0.05) than those infected with NAS strains. It was observed that the proportion
      of NAR strains increased gradually over the years. These strains had a
      significantly higher range of MIC of ciprofloxacin (0.023-1.0 microg/ml) as
      compared to the NAS strains (0.002-0.125 microg/ml) (p value < 0.05). The
      sequencing of quinolone resistance determining region (QRDR) of the gyrA gene
      showed the presence of mutation at either Ser 83 or at Asp 87 in all the NAR and
      NAI strains. None of the NAS strains had a mutation, suggesting that the gyrA
      gene mutation is sufficient to confer resistance to nalidixic acid and reduced
      susceptibility to ciprofloxacin. This mutation, although phenotypically expressed
      as decreased susceptibility to ciprofloxacin, goes undetected by the disk
      diffusion method using the present NCCLS guidelines. Hence, it can increase
      morbidity and mortality due to delay in appropriate antibiotic treatment.

PMID- 15256031
TI  - Molecular genotyping of methicillin-resistant Staphylococcus aureus strains in a
      teaching hospital in Turkey.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of
      nosocomial infections in our hospital. Therefore, we aimed to characterize MRSA
      isolates phenotypically from patients with nosocomial infections at Cumhuriyet
      University Hospital between December, 1999, and June, 2001, in Sivas by analysis
      of antibiotic patterns and genotypically using pulsed-field gel electrophoresis
      (PFGE) and repetitive element sequence-based polymerase chain reaction (rep-PCR).
      Forty-three nosocomial isolates were collected from various wards. All isolates
      were resistant to penicillin, tetracycline, oxacillin, and gentamicin. By rep-PCR
      and by separation of SmaI fragments of genomic DNA using PFGE, one major type
      (eight subtypes with PFGE) was identified among the strains. This clone was found
      to be different than some clones such as Iberian, Brazilian, and a major clone
      that was found in another Turkish University Hospital in Ankara. According to our
      results, there is a major MRSA clone with a potential to spread in our hospital.
      Infection control measures should be directed toward restricting the further
      spread of this clone. Therefore, in accordance with these findings, a
      surveillance culturing program should be established.

PMID- 15256032
TI  - An international multicenter study of antimicrobial resistance and typing of
      hospital Staphylococcus aureus isolates from 21 laboratories in 19 countries or
      states.
AB  - During 1996, 4065 consecutive Staphylococcus aureus strains from different
      patients were collected in 21 worldwide hospital laboratories. The strains, their
      resistance pattern, and hospital demographic data were forwarded to Statens Serum
      Institut where the strains were typed and data analyzed. Resistance patterns
      varied by region and resistance to other antibiotics than methicillin were mainly
      related to the occurrence of methicillin resistance, except for mupirocin,
      rifampicin, and fusidic acid. Methicillin-resistant S. aureus (MRSA) occurred
      with low levels in hospitals in Northern Europe (<1%), increasing levels in
      middle-European countries, United States, New Zealand, and Australia (6-22%), and
      very high levels in Southern European countries as well as in parts of the United
      States, Asia, and South Africa (28-63%). MRSA found in large hospitals were more
      resistant to other antibiotics than MRSA found in smaller hospitals serviced by
      the same laboratory. No difference in resistance levels was seen for methicillin
      susceptible S. aureus (MSSA) isolated in large or small hospitals. Intensive Care
      Units had the highest level of MRSA. Strains from the lower respiratory tract
      showed the highest resistance levels and blood isolates the lowest. A dominating
      MRSA clone was found in hospitals with an MRSA frequency of more than 10%. Pulsed
      field gel electrophoresis (PFGE) typing recognized several of these clones as
      international epidemic MRSA (E-MRSA). All MSSA isolates were phage typed
      (typeability 85.4%) and divided in seven major phage patterns. Isolates of all
      patterns were found in all hospitals except one, indicating that the MSSA seldom
      represented the spread of clones within the hospital. The comparison should
      evaluate the prevalence of community-acquired MRSA and identify internationally E
      MRSA. The present study gives a snapshot of the MRSA situation, but it is
      important to build up a continuous national and international surveillance,
      because MRSA is a global socioeconomic problem. Global infection control
      procedures, including rational antibiotic use, should be agreed on. The
      accompanying paper will address the issue of antibiotic consumption and MRSA.

PMID- 15256033
TI  - An international multicenter study of antimicrobial consumption and resistance in
      Staphylococcus aureus isolates from 15 hospitals in 14 countries.
AB  - Antibiotic consumption during 1996 was measured in 15 large hospitals from 14
      countries and 3000 consecutive Staphylococcus aureus samples were collected,
      allowing calculation of local resistance rates and typing of isolates. Antibiotic
      consumption data were converted to defined daily doses (DDD), and similar
      antibiotics were grouped if they belonged to the same therapeutic subgroup.
      Variations in hospital size were corrected by using DDD per 1000 bed-days. The
      total antibiotic consumption in the 15 hospitals varied between 296 DDD/1000 bed
      days and 1108 DDD/1000 bed-days. Differences in the usage of therapeutical
      subgroups of antimicrobials varied significantly between hospitals. A positive
      correlation was found between S. aureus resistance to methicillin (MRSA) and
      consumption of beta-lactam combinations, between resistance to quinolones and
      consumption of beta-lactam combinations and carbapenems and resistance to
      aminoglycosides and consumption of beta-lactam combinations. The consumption of
      beta-lactamase-sensitive antibiotics was negatively correlated to resistance to
      methicillin, quinolones, and aminoglycosides. Usage of the different
      antimicrobial therapeutical subgroups was also correlated. Consumption of beta
      lactamase-sensitive antibiotics (penicillin) was positively correlated to
      consumption of beta-lactamase-resistant penicillins and negatively correlated to
      consumption of carbapenems, quinolones, and glycopeptides, whereas consumption of
      cephalosporins was positively correlated to consumption of aminoglycosides,
      quinolones, and glycopeptides. In this study of hospitals with MRSA prevalence of
      between 0% and 63%, significant correlations were found between resistance and
      consumption of antimicrobials. These findings support the importance of
      antimicrobial consumption on resistance. An accompanying paper addresses the
      issue of antibiotic resistance and clonality of isolates.

PMID- 15256034
TI  - Vancomycin-resistant enterococcus (VRE) carriage and infection in intensive care
      units.
AB  - From July, 1997, through December, 2001, patients who were admitted to intensive
      care units (ICUs) were enrolled in the study of vancomycin resistance
      enterococcus (VRE) colonization. Among 4,538 patients admitted to the ICUs, 363
      (8.0%) patients were found to have positive culture of VRE at the day of
      admission to the ICUs and 453 (10.0%) of patients were negative to the first day
      of admission but became colonized with VRE during the stay in ICU. Among 816
      patients, 9 (1.1%) with VRE isolated from sterile sites were selected for further
      analysis. Pulsed-field gel electrophoresis (PFGE) revealed a total of four PFGE
      banding patterns in the colonized and infected Enterococcus faecium isolates. Six
      of nine 9 were found to have an identical PFGE type Ia, suggesting the
      circulation of an endemic strain. All of these type Ia isolates also contained
      two potential virulence genes, the esp and hly genes and were first identified in
      Asia. After the further typing of 540 isolates that were randomly selected from
      each month, the endemic strain was not identified before the first patient was
      colonized and infected with this strain in November, 1998, but was isolated from
      other ICU patients during each month thereafter throughout the remainder of the
      study period. Although colonization of VRE is the first step toward infection, a
      low infection rate was observed, except in patients with prolonged
      hospitalization and severe illness. Use of the isolation room and reminders
      regarding hand hygiene failed to prevent the circulation of endemic strain. Thus,
      the SHEA guideline (Muto et al., Infect. Control Hosp. Epidemiol. 2003;24:362
      386) for preventing nosocomial transmission of VRE should be enforced.

PMID- 15256035
TI  - Detection of extended-spectrum beta-lactamase-producing, multidrug-resistant
      environmental isolates of Escherichia coli that bind to human bladder cells.
AB  - Compared to the number of studies examining extended-spectrum beta-lactamase
      (ESBL)-producing clinical isolates, environmental ESBL-producers have not been
      studied extensively. To investigate environmental ESBL-producing Escherichia
      coli, 22 cephalothin-resistant E. coli were isolated from Han River in Seoul,
      Korea. These isolates were resistant to ampicillin, cephalothin, and gentamicin,
      and 14 isolates among these were resistant to norfloxacin. All of these isolates
      produce AmpC and CMY, OXA, or TEM as determined by isoelectric point focusing
      (IEF) gel electrophoresis and PCR. One isolate (57-214) producing AmpC and OXA
      was resistant to all antibiotics (ampicillin, cephalothin, norfloxacin,
      gentamicin, cefotaxime, ceftazidime) tested in this study. Six isolates,
      including isolate 57-214, could adhere to T24 human bladder cells, and these
      isolates were not related to each other as shown with random amplified
      polymorphic DNA (RAPD). Results showed that environmental ESBL-producing E. coli
      is able to colonize in bladder cells and directly cause antibiotic-resistant
      urinary tract infection.

PMID- 15256036
TI  - Differences in health care in South Africa and the UK.

PMID- 15256037
TI  - E-mail consultations in general practice.

PMID- 15256038
TI  - Bacterial vaginosis: not a risk factor for preterm birth?

PMID- 15256039
TI  - It's never too late: calorie restriction is effective in older mammals.

PMID- 15256040
TI  - Watch your notch: a link between aging and stem cell fate?

PMID- 15256041
TI  - Why use telomerized cells for organ transplantation?

PMID- 15256042
TI  - Tissue engineering and regenerative medicine: concepts for clinical application.
AB  - Patients suffering from diseased and injured organs may be treated with
      transplanted organs. However, there is a severe shortage of donor organs that is
      worsening yearly given the aging population. Scientists in the field of
      regenerative medicine and tissue engineering apply the principles of cell
      transplantation, material science, and bioengineering to construct biological
      substitutes that will restore and maintain normal function in diseased and
      injured tissues. Therapeutic cloning, where the nucleus from a donor cell is
      transferred into an enucleated oocyte in order to extract pluripotent embryonic
      stem cells, offers a potentially limitless source of cells for tissue engineering
      applications. The stem cell field is also advancing rapidly, opening new options
      for therapy. This paper reviews recent advances that have occurred in
      regenerative medicine and describes applications of these new technologies that
      may offer novel therapies for patients with end-stage organ failure.

PMID- 15256043
TI  - Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless
      descendants of Mexican hairless dogs.
AB  - The depigmenting and anti-aging effects of kinetin (KN) solutions on the aged
      skin of hairless dogs were clinically and histologically investigated. Grossly,
      all KN-treated sites became mildly depigmented. At 50 days of topical treatment
      with KN solutions, apparent improvement was observed in the skin texture,
      wrinkling, and pigmentation. At 100 days of KN treatment, both the skin
      rejuvenation and depigmentation effects became more prominent. Throughout the
      experimental period of KN treatment, no adverse effects were found in any sites
      treated with KN solutions. In the colorimetric system, at 100 days of topical
      treatment with KN solutions, the L* and b* values in the sites treated with KN
      solutions significantly increased. Histologically, at 50 days of topical
      treatment with KN solutions, the KN-treated sites showed a decrease in the
      thickness of the corneal layers. Melanin granules decreased throughout all
      epidermal layers. In the dermis, the large number of fine collagen and elastic
      fibers were densely aligned. At the end of the treatment, this agent was equally
      effective against pigmented lesions irrespective of the concentration of KN
      solution. The distribution of melanin granules returned to normal in the skin of
      adult hairless dogs. Throughout the present study, there were no histologic
      abnormalities in the epidermis and the dermis. These results revealed that
      topical treatment with lower concentrations of KN solutions normalized
      hyperpigmentation and improved the aged skin structure of hairless dogs. In
      addition, it was clarified that KN solutions had no adverse effects on the skin
      of hairless dogs and that this agent was a safe chemical for long-term
      application.

PMID- 15256044
TI  - Hormetic mechanisms of anti-aging and rejuvenating effects of repeated mild heat
      stress on human fibroblasts in vitro.
AB  - The phenomenon of hormesis is represented by mild stress-induced stimulation of
      maintenance and repair pathways, resulting in beneficial effects for cells and
      organisms. We have reported that repeated mild heat stress (RMHS) has anti-aging
      hormetic effects on growth and various cellular and biochemical characteristics
      of human skin fibroblasts undergoing aging in vitro. These effects of RMHS
      include the maintenance of the stress protein profile, reduction in the
      accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of
      the activities of the proteasome and its 11S activator, improvement in cellular
      resistance to ethanol, hydrogen peroxide, and ultraviolet rays, and increased
      antioxidative activity of the cells. We have also reported that RMHS prolongs the
      lifespan of Drosophila. Others have reported anti-aging and life prolonging
      effects of a wide variety of so-called stressors, such as pro-oxidants,
      aldehydes, calorie restriction, irradiation, heat shock, and hypergravity.
      Although molecular mechanisms of hormesis are yet to be elucidated, there are
      indications that relatively small hormetic effects become biologically amplified,
      resulting in significant improvement of cellular and organic functions and
      survival. Hormesis, therefore, can be an effective approach for modulating aging,
      for preventing or delaying the onset of age-related diseases, and for improving
      the quality of life in old age.

PMID- 15256045
TI  - Someone's knocking on the laboratory door.

PMID- 15256046
TI  - A new age for aging? Ethical questions, scientific insights, and societal
      outcomes.

PMID- 15256047
TI  - An interview with Michael West. Interviewed by Vicki Glaser.

PMID- 15256048
TI  - Science of Aging Knowledge Environment (SAGE KE). Interview by Vicki Glaser.

PMID- 15256049
TI  - Literature watch.

PMID- 15256051
TI  - Resistance to platinum-containing chemotherapy in testicular germ cell tumors is
      associated with downregulation of the protein kinase SRPK1.
AB  - Male germ cell tumors (GCTs) are extremely sensitive to platinum-containing
      chemotherapy, with only 10% of patients showing therapy resistance. However, the
      biological basis of the high curability of disseminated GCTs by chemotherapy is
      still unknown. Recently, we demonstrated that the mammalian serine/arginine-rich
      protein-specific kinase 1 (SRPK1) is a cisplatin-sensitive gene, inactivation of
      which leads to cisplatin resistance. Because, in mammalians, the expression of
      SRPK1 is preferentially high in testicular tissues, cisplatin responsiveness of
      male GCTs might be associated with SRPK1 levels. In the present study, we
      monitored SRPK1 protein expression in a unique series of nonseminomatous GCTs by
      immunohistochemistry. Randomly selected GCTs (n = 70) and tumors from patients
      responding to standard chemotherapy (n = 20) generally showed strong SRPK1
      staining. In contrast, expression in refractory GCTs (n = 20) as well as in GCTs
      from poor-prognosis patients responding to high-dose chemotherapy only (n = 11)
      was significantly lower (two-sided Wilcoxon rank sum test: P < .001). In
      conclusion, our data suggest that SRPK1 expression might be an important
      prognostic indicator for the chemoresponsiveness of nonseminomatous GCTs.

PMID- 15256052
TI  - Detection and isolation of circulating tumor cells in urologic cancers: a review.
AB  - The American Cancer Society has estimated that in 2003, there will be
      approximately 239,600 new cases of urologic cancer diagnosed and 54,600 urologic
      cancer-related deaths in the United States. To date, the majority of research and
      therapy design have focused on the microenvironment of the primary tumor site, as
      well as the microenvironment of the metastatic or secondary (target) tumor site.
      Little attention has been placed on the interactions of the circulating tumor
      cells and the microenvironment of the circulation (i.e., the third
      microenvironment). The purpose of this review is to present the methods for the
      detection and isolation of circulating tumor cells and to discuss the importance
      of circulating tumor cells in the biology and treatment of urologic cancers.

PMID- 15256053
TI  - Medulloblastoma: molecular genetics and animal models.
AB  - Medulloblastoma is a primary brain tumor found in the cerebellum of children. The
      tumor occurs in association with two inherited cancer syndromes: Turcot syndrome
      and Gorlin syndrome. Insights into the molecular biology of the tumor have come
      from looking at alterations in the genes altered in these syndromes, PTC and APC,
      respectively. Murine models of medulloblastoma have been constructed based on
      these alterations. Additional murine models that, while mimicking the appearance
      of the human tumor, seem unrelated to the human tumor's molecular alterations
      have been made. In this review, the clinical picture, origin, molecular biology,
      and murine models of medulloblastoma are discussed. Although a great deal has
      been discovered about this tumor, the genetic alterations responsible for tumor
      development in a majority of patients have yet to be described.

PMID- 15256054
TI  - Human cytomegalovirus infection of tumor cells downregulates NCAM (CD56): a novel
      mechanism for virus-induced tumor invasiveness.
AB  - Pathologic data indicate that human cytomegalovirus (HCMV) infection might be
      associated with the pathogenesis of several human malignancies. However, no
      definitive evidence of a causal link between HCMV infection and cancer
      dissemination has been established to date. This study describes the modulation
      of the invasive behavior of NCAM-expressing tumor cell lines by HCMV.
      Neuroblastoma (NB) cells, persistently infected with the HCMV strain AD169 (UKF
      NB-4AD169 and MHH-NB-11AD169), were added to endothelial cell monolayers and
      adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of
      the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and
      reverse transcription-polymerase chain reaction (RT-PCR). The relevance of NCAM
      for tumor cell binding was proven by treating NB with NCAM antisense
      oligonucleotides or NCAM transfection. HCMV infection profoundly increased the
      number of adherent and penetrated NB, compared to controls. Surface expression of
      NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to
      mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA
      levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM
      expression and adhesion capacity of NB has been shown by antisense and
      transfection experiments. We conclude that HCMV infection leads to downregulation
      of NCAM receptors, which is associated with enhanced tumor cell invasiveness.

PMID- 15256055
TI  - Integrin expression regulates neuroblastoma attachment and migration.
AB  - Neuroblastoma (NBL) is the most common malignant disease of infancy, and children
      with bone metastasis have a mortality rate greater than 90%. Two major classes of
      proteins, integrins and growth factors, regulate the metastatic process. We have
      previously shown that tumorigenic NBL cells express higher levels of the type I
      insulin-like growth factor receptor (IGF-IR) and that beta1 integrin expression
      is inversely proportional to tumorigenic potential in NBL. In the current study,
      we analyze the effect of beta1 integrin and IGF-IR on NBL cell attachment and
      migration. Nontumorigenic S-cells express high levels of beta1 integrin, whereas
      tumorigenic N-cells express little beta1 integrin. Alterations in beta1 integrin
      are due to regulation at the protein level, as translation is decreased in N-type
      cells. Moreover, inhibition of protein synthesis shows that beta1 integrin is
      degraded more slowly in S-type cells (SHEP) than in N-type cells (SH-SY5Y and
      IMR32). Inhibition of alpha5beta1 integrin prevents SHEP (but not SH-SY5Y or
      IMR32) cell attachment to fibronectin and increases SHEP cell migration.
      Increases in IGF-IR decrease beta1 integrin expression, and enhance SHEP cell
      migration, potentially through increased expression of alphavbeta3. These data
      suggest that specific classes of integrins in concert with IGF-IR regulate NBL
      attachment and migration.

PMID- 15256056
TI  - Tumor-targeted hyaluronan nanoliposomes increase the antitumor activity of
      liposomal Doxorubicin in syngeneic and human xenograft mouse tumor models.
AB  - Naturally occurring high-Mr hyaluronan, bound to the surface of nanoliposomes
      (denoted targeted hyaluronan liposomes, or tHA-LIP), is a candidate for active
      targeting to tumors, many of which overexpress the hyaluronan receptors CD44 and
      RHAMM. The surface-bound hyaluronan also provides a hydrophilic coat that,
      similar to polyethylene glycol, may promote long-term circulation. We recently
      reported the successful targeting of mitomycin C, mediated by tHA-LIP, in tumor
      bearing syngeneic mice. Hypothesizing that this targeting is carrier-specific,
      rather than drug-specific, we report here studies with doxorubicin (DXR)-loaded
      tHA-LIP, in syngeneic and human xenograft models. Saline, free DXR, DXR-loaded
      nontargeted liposomes (nt-LIP), and Doxil served as controls. The tHA-LIP were
      long-circulating, more than all controls, in healthy and tumor-bearing
      (C57BL/6/B16F10.9; BALB/c/C-26) mice. Mediated by tHA-LIP, DXR accumulation in
      tumor-bearing lungs was 30-, 6.7-, and 3.5-fold higher than free DXR, nt-LIP, and
      Doxil, respectively. Key indicators of therapeutic responses--tumor progression,
      metastatic burden, and survival--were superior (P < .001) in animals receiving
      DXR-loaded tHA-LIP compared with controls, in tumor-bearing syngeneic mice
      (BDF1/P388/ADR ascites, C57BL/6/B16F10.9 lung metastasis, and BALB/c/C-26 solid
      tumors), and in nude mice bearing PANC-1 solid tumors. In conclusion, tHA-LIP,
      performing as tumor-targeted carriers, have the potential to join the arsenal of
      carrier-formulated anticancer drugs.

PMID- 15256057
TI  - Regulation of gene expression and inhibition of experimental prostate cancer bone
      metastasis by dietary genistein.
AB  - Prostate cancer frequently metastasizes to the bone, and the treatment outcome
      for metastatic prostate cancer has been disappointing so far. Dietary genistein,
      derived primarily from soy product, has been proposed to be partly responsible
      for the low rate of prostate cancer in Asians. Our previous studies have shown
      that genistein elicits pleiotropic effects on prostate cancer cells, but there
      are no studies documenting comprehensive gene expression profiles and antitumor
      effects of dietary genistein on human prostate cancer grown in human bone
      environment. In this study, we investigated the effects of genistein on PC3
      prostate cancer cells and experimental PC3 bone tumors created by injecting PC3
      cells into human bone fragments previously implanted in severe combined
      immunodeficient (SCID) mice (SCID human model). We found that genistein
      significantly inhibited PC3 bone tumor growth using both prevention and
      intervention strategies. By using microarray and real-time polymerase chain
      reaction technology, we found that genistein regulated the expression of multiple
      genes involved in the control of cell growth, apoptosis, and metastasis both in
      vitro and in vivo. For example, the expression of various metalloproteinases
      (MMPs) in PC3 bone tumors was inhibited by genistein treatment, whereas
      osteoprotegerin was upregulated. MMP immunostaining and transfection experiments
      also demonstrated that MMP-9 expression was inhibited in PC3 cells in vitro and
      PC3 bone tumors in vivo after genistein treatment. These results, particularly
      the in vivo results, demonstrate that dietary genistein may inhibit prostate
      cancer bone metastasis by regulating metastasis-related genes. Genistein may thus
      be a promising agent for the prevention and/or treatment of prostate cancer.

PMID- 15256058
TI  - Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand.
AB  - Starting from the observation that tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)/Apo-2L protein is expressed in both malignant and
      inflammatory cells in some highly vascularized soft tissue sarcomas, the
      angiogenic potential of TRAIL was investigated in a series of in vitro assays.
      Recombinant soluble TRAIL induced endothelial cell migration and vessel tube
      formation to a degree comparable to vascular endothelial growth factor (VEGF),
      one of the best-characterized angiogenic factors. However, the proangiogenic
      activity of TRAIL was not mediated by endogenous expression of VEGF. Although
      TRAIL potentiated VEGF-induced extracellular signal-regulated kinase (ERK)
      phosphorylation and endothelial cell proliferation, the combination of TRAIL +
      VEGF did not show additive effects with respect to VEGF alone in inducing vessel
      tube formation. Thus, although TRAIL has gained attention as a potential
      anticancer therapeutic for its ability to induce apoptosis in a variety of cancer
      cells, our present data suggest that TRAIL might also play an unexpected role in
      promoting angiogenesis, which might have therapeutic implications.

PMID- 15256059
TI  - High-resolution X-ray microtomography for the detection of lung tumors in living
      mice.
AB  - In the present study, the feasibility of applying high-resolution microtomography
      (micro-CT) for the detection of lung tumors was investigated in live mice at an
      early and more advanced stage of tumor development. The chest area of
      anesthesized mice was scanned by X-ray micro-CT. In mice with a minor and heavy
      tumor load, micro-CT proved to be a fast and noninvasive imaging device for the
      detection of lung tumors. After validation of the CT data by histologic
      sectioning, it was shown that the majority of tumors could be distinguished in
      the reconstructed virtual slices obtained by micro-CT. The data from micro-CT
      were also confirmed by visual inspection of the inflated and excised lungs
      postmortem. In vivo micro-CT opens broad perspectives for imaging tumor
      development and its progression in a noninvasive way. Micro-CT also allows for
      longitudinal evaluation of the treatment of lung cancer by drugs.

PMID- 15256060
TI  - Aberrant methylation of the maspin promoter is an early event in human breast
      cancer.
AB  - The maspin gene functions as a tumor suppressor in human breasts, and its
      expression is frequently lost during breast cancer progression. In vitro models
      of human breast cancer indicate that the loss of maspin expression is closely
      linked to aberrant methylation of the maspin promoter. We conducted a study on 30
      archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant
      methylation of the maspin promoter occurred in vivo, and whether it occurred
      early in breast cancer evolution. Healthy tissue obtained from reduction
      mammoplasty was used as normal control. Results from immunohistochemical analysis
      indicate that maspin expression is lost in a substantial fraction of DCIS
      specimens (57%). Bisulfite sequencing of DNA isolated from laser capture
      microdissected normal and neoplastic ducts showed that loss of maspin expression
      was often, but not always, linked to aberrant methylation of the maspin promoter,
      suggesting that other mechanisms, in addition to aberrant methylation,
      participate and/or cooperate to silence maspin gene expression. Taken together,
      these results indicate that aberrant methylation of the maspin promoter is an
      early event in human breast cancer.

PMID- 15256062
TI  - Overexpression of dimethylarginine dimethylaminohydrolase enhances tumor hypoxia:
      an insight into the relationship of hypoxia and angiogenesis in vivo.
AB  - The oxygenation status of tumors derived from wild-type C6 glioma cells and clone
      D27 cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH) was
      assessed in vivo using a variety of direct and indirect assays of hypoxia. Clone
      D27 tumors exhibit a more aggressive and better-vascularized phenotype compared
      to wild-type C6 gliomas. Immunohistochemical analyses using the 2-nitroimidazole
      hypoxia marker pimonidazole, fiber optic OxyLite measurements of tumor pO2, and
      localized 31P magnetic resonance spectroscopy measurements of tumor bioenergetic
      status and pH clearly demonstrated that the D27 tumors were more hypoxic compared
      to C6 wild type. In the tumor extracts, only glucose concentrations were
      significantly lower in the D27 tumors. Elevated Glut-1 expression, a reliable
      functional marker for hypoxia-inducible factor-1-mediated metabolic adaptation,
      was observed in the D27 tumors. Together, the data show that overexpression of
      DDAH results in C6 gliomas that are more hypoxic compared to wild-type tumors,
      and point strongly to an inverse relationship of tumor oxygenation and
      angiogenesis in vivo--a concept now being supported by the enhanced understanding
      of oxygen sensing at the molecular level.

PMID- 15256061
TI  - Nuclear factor-kappaB/p65 (Rel A) is constitutively activated in human prostate
      adenocarcinoma and correlates with disease progression.
AB  - Aberrant nuclear factor-kappaB (NF-kappaB) activation has been implicated in the
      pathogenesis of several human malignancies. In this study, we determined whether
      NF-kappaB is constitutively activated in human prostate adenocarcinoma, and, if
      so, whether increased NF-kappaB activation and its binding to DNA influence tumor
      progression. Using tissue samples obtained during transurethral prostatic
      resection and paraffin-embedded sections of benign and cancer specimens, we
      determined the nuclear expression of NF-kappaB/p65 and NF-kappaB/p50, cytoplasmic
      expression of IkappaBalpha, its phosphorylation, and expression of NF-kappaB
      regulated genes, specifically Bcl2, cyclin D1, matrix metalloproteinase-9 (MMP
      9), and vascular endothelial growth factor (VEGF). A progressive increase in the
      expression of NF-kappaB/p65 (but not of p50) was observed in cancer specimens
      compared to benign tissue, which correlated with increasing levels of
      IkappaBalpha and its phosphorylation. NF-kappaB DNA-binding activity increased
      with increasing tumor grade and the binding complex mainly consisted of NF
      kappaB/p65-p50 heterodimers. Immunohistochemical analysis showed enhanced nuclear
      staining for NF-kappaB/p65 in both high-grade (P <.0001) and low-grade (P <.003)
      cancer specimens, compared to benign tissue. The nuclear levels of NF-kappaB/p65
      correlated with concurrent increase in cytosolic levels of IkappaBalpha along
      with NF-kappaB-dependent expression of Bcl2, cyclin D1, MMP-9, and VEGF. These
      results demonstrate that NF-kappaB/p65 is constitutively activated in human
      prostate adenocarcinoma and is related to tumor progression due to
      transcriptional regulation of NF-kappaB-responsive genes.

PMID- 15256064
TI  - Intracellular calcium signals and control of cell proliferation: how many
      mechanisms?
AB  - The progression through the cell cycle in non-transformed cells is under the
      strict control of extracellular signals called mitogens, that act by eliciting
      complex cascades of intracellular messengers. Among them, increases in cytosolic
      free calcium concentration have been long realized to play a crucial role;
      however, the mechanisms coupling membrane receptor activation to calcium signals
      are still only partially understood, as are the pathways of calcium entry in the
      cytosol. This article centers on the role of calcium influx from the
      extracellular medium in the control of proliferative processes, and reviews the
      current understanding of the pathways responsible for this influx and of the
      second messengers involved in their activation.

PMID- 15256063
TI  - Aberrant gene expression in human non small cell lung carcinoma cells exposed to
      demethylating agent 5-aza-2'-deoxycytidine.
AB  - The identification of genes undergoing genetic or epigenetic alterations and
      contributing to the development of cancer is critical to our understanding of the
      molecular mechanisms of carcinogenesis. A new approach in identifying alterations
      of genes that might be relevant to the process of tumor development was used in
      this study by examining the gene expression profile in human lung cancer cells
      exposed to 5-aza-2'-deoxycytidine (5-aza-dC). A cDNA array analysis was carried
      out on 5-aza-dC-treated and untreated non small cell lung cancer (NSCLC) cell
      line NCI-H522. Sixteen and 14 genes were upregulated and downregulated,
      respectively, by 5-aza-dC treatment. Among them, downregulation of tyrosine
      protein kinase ABL2 (ABL2) gene and upregulation of hint/protein kinase C
      inhibitor 1 (Hint/PKCI-1), DVL1, TIMP-1, and TRP-1 genes were found in expanded
      observations in two or three of five 5-aza-dC-treated NSCLC cell lines. Among
      these genes, we found that cDNA transfer of Hint/PKCI-1 resulted in a significant
      in vitro growth inhibition in two cell lines exhibiting 5-aza-dC-induced
      upregulation of Hint/PKCI-1 and significantly reduced in vivo tumorigenicity of
      one NSCLC cell line. Hint/PKCI-1, which is the only other characterized human
      histidine triad (HIT) nucleotide-binding protein in addition to tumor-suppressor
      gene FHIT, might be involved in lung carcinogenesis.

PMID- 15256065
TI  - Soluble, insoluble and geometric signals sculpt the architecture of mineralized
      tissues.
AB  - Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the
      transforming growth factor-beta (TGF-beta) superfamily, are soluble mediators of
      tissue morphogenesis and induce de novo endochondral bone formation in
      heterotopic extraskeletal sites as a recapitulation of embryonic development. In
      the primate Papio ursinus, the induction of bone formation has been extended to
      the TGF-beta isoforms per se. In the primate and in the primate only, the TGF
      beta isoforms are initiators of endochondral bone formation by induction and act
      in a species-, site- and tissue-specific mode with robust endochondral bone
      induction in heterotopic sites but with limited new bone formation in orthotopic
      bone defects. The limited inductive capacity orthotopically of TGF-beta isoforms
      is associated with expression of the inhibitory Smads, Smad6 and Smad7. In
      primates, bone formation can also be induced using biomimetic crystalline
      hydroxyapatite matrices with a specific surface geometry and without the
      exogenous application of osteogenic proteins of the TGF-beta superfamily, even
      when the biomimetic matrices are implanted heterotopically in the rectus
      abdominis muscle. The sequence of events that directs new bone formation upon the
      implantation of highly crystalline biomimetic matrices initiates with vascular
      invasion, mesenchymal cell migration, attachment and differentiation of
      osteoblast-like cells attached to the substratum, expression and synthesis of
      osteogenic proteins of the TGF-beta superfamily resulting in the induction of
      bone as a secondary response. The above findings in the primate indicate enormous
      potential for the bioengineering industry. Of particular interest is that
      biomimetic matrices with intrinsic osteoinductivity would be an affordable option
      in the local context.

PMID- 15256066
TI  - Ca2+ and mitochondria as substrates for deficits in synaptic plasticity in normal
      brain ageing.
AB  - Normal brain ageing is associated with a degree of functional impairment of
      neuronal activity that results in a reduction in memory and cognitive functions.
      One mechanism proposed to explain the age-dependent changes was the "Ca(2+)
      hypothesis of ageing" but data accumulated in the last decade revealed a number
      of inconsistencies. Two important questions were raised: (a) which are, if any,
      the most reliable age-associated change in neuronal Ca(2+) homeostasis and (b)
      are these changes primary, and thus determinant of the ageing phenotype, or are
      they secondary to other changes in the physiology of the aged neurones. After a
      brief review of the evidence accumulated for the age-induced changes in synaptic
      plasticity, we assess the proposal that these changes are, ultimately, determined
      by changes in the metabolic state of the aged neurones, that are manifest
      particularly after neuronal stimulation. In this context, it appears that the
      changes in mitochondrial status and function are of primary importance.

PMID- 15256067
TI  - Inorganic phosphate homeostasis and the role of dietary phosphorus.
AB  - Inorganic phosphate (Pi) is required for cellular function and skeletal
      mineralization. Serum Pi level is maintained within a narrow range through a
      complex interplay between intestinal absorption, exchange with intracellular and
      bone storage pools, and renal tubular reabsorption. The crucial regulated step in
      Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II
      sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in
      the renal proximal tubule and is regulated by Pi, parathyroid hormone and by 1,25
      dihydroxyvitamin D. Recent studies of inherited and acquired hypophosphatemia [X
      linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant
      hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced
      rickets/osteomalacia (TIO)], which exhibit similar biochemical and clinical
      features, have led to the identification of novel genes, PHEX and FGF23, that
      play a role in the regulation of Pi homeostasis. The PHEX gene, which is mutated
      in XLH, encodes an endopeptidase, predominantly expressed in bone and teeth, but
      not in kidney. FGF-23 may be a substrate of this endopeptidase and may therefore
      accumulate in patients with XLH. In the case of ADHR mutations in the furin
      cleavage site, which prevent the processing of FGF-23 into fragments, lead to the
      accumulation of a "stable" circulating form of the peptide which also inhibits
      renal Pi reabsorption. In the case of TIO, ectopic overproduction of FGF-23
      overwhelms its processing and degradation by PHEX, leading to the accumulation of
      FGF-23 in the circulation and inhibition of renal Pi reabsorption. Mice
      homozygous for severely hypomorphic alleles of the Klotho gene exhibit a syndrome
      resembling human aging, including atherosclerosis, osteoporosis, emphysema, and
      infertility. The KLOTHO locus is associated with human survival, defined as
      postnatal life expectancy, and longevity, defined as life expectancy after 75. In
      considering the relationship of klotho expression to the dietary Pi level, the
      klotho protein seemed to be negatively controlled by dietary Pi.

PMID- 15256068
TI  - S-glutathionylation: from redox regulation of protein functions to human
      diseases.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an
      integral role in the modulation of several physiological functions but can also
      be potentially destructive if produced in excessive amounts. Protein cysteinyl
      thiols appear especially sensitive to ROS/RNS attack. Experimental evidence
      started to accumulate recently, documenting that S-glutathionylation occurs in a
      number of physiologically relevant situations, where it can produce discrete
      modulatory effects on protein function. The increasing evidence of functional
      changes resulting from this modification, and the growing number of proteins
      shown to be S-glutathionylated both in vitro and in vivo support this contention,
      and confirm this as an attractive area of research. S-glutathionylated proteins
      are now actively investigated with reference to problems of biological interest
      and as possible biomarkers of human diseases associated with
      oxidative/nitrosative stress.

PMID- 15256069
TI  - Coenzyme Q10 inhibits mitochondrial complex-1 down-regulation and nuclear factor
      kappa B activation.
AB  - We have used control-homozygous weaver mutant, and -heterozygous weaver mutant
      mice in order to explore the basic molecular mechanism of neurodegeneration and
      the neuroprotective potential of coenzyme Q(10). Homozygous weaver mutant mice
      exhibited progressive neurodegeneration in the hippocampus, striatum, and
      cerebellum, and a reduction in the striatal levels of dopamine and coenzyme Qs
      (Q(9) and Q(10)) without any significant changes in norepinephrine and serotonin.
      Mitochondrial complex-1 was down regulated; whereas nuclear factor-kappa B was up
      regulated in homozygous weaver mutant mice. Rotenone inhibited complex-1,
      enhanced nuclear factor-kappa B, and caused apoptosis in human dopaminergic (SK-N
      SH) neurons; whereas nuclear factor-kappa B antibody suppressed rotenone-induced
      apoptosis, suggesting that enhancing coenzyme Q(10) synthesis and suppressing the
      induction of NF-kappa B, may provide neuroprotection.

PMID- 15256070
TI  - The comparison of different protocols for expansion of umbilical-cord blood
      hematopoietic stem cells.
AB  - Hematopoiesis is maintained by the activity of multipotent stem cells, which have
      the dual capacity to self-renew and to differentiate into all of the blood cell
      lineages. The major challenge of stem cells based regenerative therapy is to
      expand ex vivo the primitive compartment to increase transplantable stem cells
      number. The present study was designed to evaluate several culture systems for in
      vitro maintenance of umbilical cord blood stem cells. The influences of different
      growth conditions such as stromal feeder layer, cytokines supplement and
      placental conditioned medium (PCM) have been evaluated over a relatively short
      period of time on CD34(+) cell expansion and maintenance of clonogenic
      progenitors. When cells were expanded on feeder layer in the presence of added
      cytokines and PCM on average a 2.96-fold increase of CD34(+)CD71(-) and a 3.13
      fold increase of CD34(+)HLA-DR(-) was observed. The total number of colony
      forming cells (35 +/- 2.65) indicated also that the yield of clonogenic
      progenitors obtained with a combination of all factors was two folds higher than
      each of these factors alone and ten time above control (3.67 +/- 2.52). In
      conclusion, the results of our study clearly show that the ex vivo expansion of
      hematopoietic progenitor cells obtained from human umbilical cord blood is
      dependent on controlled experimental conditions, which might be helpful when
      designing culture systems for clinical applications.

PMID- 15256071
TI  - Scanning of beta-globin gene for identification of beta-thalassemia mutation in
      Romanian population.
AB  - Beta-thalassemia is uncommon (0.5%) in the Romanian population, but it must be
      considered in the differential diagnosis of hypochromic anemia. The molecular
      characterization of beta-thalassemia is absolutely necessary for molecular
      diagnosis, as well as any genetic epidemiological study in this region. Molecular
      analyses consist of mutation detection by molecular scanning of beta-globin gene.
      This gene has 3 exons and 2 introns, involved in beta-thalassemic pathogenesis.
      Clinical application of DNA analysis on beta-thalassemic chromosomes allowed
      characterization of 29 persons with different beta-thalassemia mutations among 58
      patients with anemia. The experimental strategy was based on sequential PCR
      amplification of most of the beta-globin gene and running on denaturing gradient
      gel electrophoresis of amplification products. Definitive characterization of
      mutations in samples identified with shifted DGGE patterns was performed ARMS-PCR
      and/or PCR-restriction enzyme analysis methods. Eight different beta-thalassemia
      alleles were identified, the most common being IVS I-110 (G-A) and cd 39 (C-T).
      Comparison of overall frequency of mutations in the neighboring countries, shows
      that these results are in the frame of overall distribution of these mutations in
      Mediterranean area, especially in Greece and in Bulgaria. Molecular diagnosis is
      useful for differentiating mild from severe alleles, for genetic counseling, as
      well as for mutation definition in carriers, identified by hematological analysis
      necessary for prenatal testing and genetic counseling.

PMID- 15256072
TI  - Morphological and functional changes in rat hippocampal slice cultures after
      short-term oxygen-glucose deprivation.
AB  - To study effects of short-term cerebral ischemia, hippocampal slice cultures were
      subjected to oxygen and glucose deprivation (OGD) followed by a period of
      normoxic reoxygenation. Propidium iodide staining, and MTT/formazan-assay were
      used to evaluate cell viability and metabolic activity. CA1 pyramidal cells were
      analyzed at the light- and electron microscopic levels. Cell damage was found to
      be insignificant during the first hour after 10 min OGD but profound following 4
      h, showing delayed neuronal cell damage caused by short-term OGD. Our model can
      be used to characterize the mechanisms of cell damage caused by mild cerebral
      ischemia. These data might apply to further development of neuroprotective tools
      for the treatment of brain diseases.

PMID- 15256073
TI  - Type 1 diabetes genetic susceptibility encoded by HLA DQB1 genes in Romania.
AB  - Most cases of type 1 diabetes (T1DM) are due to an immune-mediated destruction of
      the pancreatic beta cells, a process that is conditioned by multiple genes and
      environmental factors. The main susceptibility genes are represented by the class
      II HLA-DRB1 and DQB1 alleles. The aim of our study was to reconfirm the
      contribution of HLA-DQB1 polymorphisms to T1DM genetic susceptibility for the
      Romanian population. For this, 219 Romanian T1DM families were genotyped at high
      resolution for HLA DQB1 using the PCR-SSOP method (Polymerase Chain Reaction -
      Sequence Specific Oligonucleotide Probes). Allele transmission to diabetics and
      unaffected siblings was studied using the Transmission Disequilibrium Test (TDT).
      We found an increased transmission of DQB1*02 (77.94% transmission, p(TDT) = 7.18
      x 10(-11)) and DQB1*0302 (80.95% transmission, p(TDT) = 2.25 x 10(-10)) alleles
      to diabetics, indicating the diabetogenic effect of these alleles. Conversely,
      DQB1*0301, DQB1*0603, DQB1*0602, DQB1*0601 and DQB1*05 alleles are protective,
      being significantly less transmitted to diabetics. In conclusion, our results
      confirmed the strong effect of HLA-DQB1 alleles on diabetes risk in Romania, with
      some characteristics which can contribute to the low incidence of T1DM in this
      country.

PMID- 15256074
TI  - Expression of Dishevelled-1 in wound healing after acute myocardial infarction:
      possible involvement in myofibroblast proliferation and migration.
AB  - One of our previous studies indicated that the expression of beta-catenin, which
      is the key factor of wnt-frizzled pathway, increased significantly in the
      ischemic area of the rat heart 7 days after myocardial infarction (MI). Together
      with the results of other recent studies, we made an assumption that wnt-frizzled
      pathway may be involved in the controlled cell proliferation and migration during
      repair processes after MI. To verify this assumption we tried to investigate the
      expression of another signal transduction molecule called Dishevelled in wnt
      frizzled pathway during the wound healing process after MI. The left descending
      coronary arteries of rats were ligated to induce MI. Immunohistochemistry SABC
      method and in situ hybridization were performed to detect the expression of
      Dishevelled-1. The results showed, that one day after MI, Dishevelled-1 mRNA but
      not protein expression was detected in the cells at the border zone of the
      infarction area; 4 days after MI the expression of Dishevelled-1 increased
      exclusively and cytoplasmic Dishevelled-1 was observed not only at the border
      zone but also in the infarct area; 7 days after MI, it seems that the expression
      reached its peak, the positive staining even spread into the endothelial and
      smooth muscle cells of the newly formed and pre-existing blood vessels in the
      infarction area; after that the Dishevelled-1 expression decreased abruptly and
      could hardly be detected 28 days after MI. Thus cytoplasmic Dishevelled-1 may be
      involved in the controlled proliferation and migration of myofibroblasts and
      vascular endothelial cells, hence play a role during the wound healing process
      after MI.

PMID- 15256075
TI  - MHC class II vesicles (CIIV) within immature dendritic cells.

PMID- 15256076
TI  - Kinetic logic: a tool for describing the dynamics of infectious disease behavior.
AB  - Most of the infectious diseases imply biological regulations controlled by
      several feedback loops or circuits. Kinetic logic, which is a method easily
      accessible to biologists or physicians, and which takes time and thresholds of
      activity into account, seems a convenient method for building simplified models
      related to this field. This implies usually qualitative predictions concerning
      the dynamics of such biological systems, leading to a movement back and forth
      between experimentation or observation and logical description. Here, we
      illustrate this simple modelling method in building elementary models concerning
      prion infection to demonstrate how to proceed. We also discuss and summarize how
      this method has been used for studying several viral diseases. As an example, we
      show how predictions related to the rhabdovirus cycle, were experimentally
      verified.

PMID- 15256077
TI  - [Idiopathic pulmonary fibrosis: a challenge to us].

PMID- 15256083
TI  - [Comparative analysis of respiratory bronchiolitis-associated interstitial lung
      disease and desquamative interstitial pneumonia].
AB  - OBJECTIVE: To investigate the clinicopathologic characteristics of respiratory
      bronchiolitis-associated interstitial lung disease (RBILD) and its relationship
      to desquamative interstitial pneumonia (DIP). METHODS: The clinical and
      pathological data of one patient with RBILD confirmed by video-assisted
      thoracoscopic lung biopsy were reviewed retrospectively, and compared with one
      patient with DIP. RESULTS: Both patients were 57 year old male, and they had a
      history of cigarette smoking for 24 and 30 years respectively. The clinical
      manifestations were cough and sputum production, breathlessness with exertion,
      and crackles on chest examination. Lung function test showed a mild abnormality
      with mixed obstructive-restrictive and restrictive pattern respectively. The
      chest radiograph showed scattered small nodules and patchy densities. High
      resolution computer tomography showed scattered interstitial infiltrates and
      reticular changes in the middle and lower lung fields, but patchy ground-glass
      attenuation was found only in DIP. The pathological examination showed the
      presence of clusters of pigmented macrophages within the lumens of respiratory
      bronchioles, alveolar ducts and peribronchiolar alveolar spaces, with patchy
      submucosal and peribronchiolar infiltration of lymphocytes and histiocytes. Mild
      peribronchiolar fibrosis was found in RBILD. Compared with RBILD, the lesions of
      DIP were more severe and widespread. Both the patients responded favorably to
      glucocorticoids. They were followed for more than three years. CONCLUSION: RBILD
      could be confused with DIP in clinical manifestations, but can be separated by
      open lung biopsy. Considering their similarities, these two lesions may be
      regarded as a same disease entity.

PMID- 15256084
TI  - [Change of prostaglandin E2 and interleukin-12, interleukin-13 in the
      bronchoalveolar lavage fluid and the serum of the patients with idiopathic
      pulmonary fibrosis].
AB  - OBJECTIVE: To detect the levels of prostaglandin E2 (PGE2) and interleukin-12 (IL
      12), IL-13 in the bronchoalveolar lavage fluid (BALF) and the serum of patients
      with idiopathic pulmonary fibrosis (IPF) and to investigate the significance of
      their change in the pathogenesis of IPF. METHODS: Radioimmunoassay (RIA) and
      enzyme-linked immunoadsorbent assay (ELISA) were used to detect the levels of
      PGE2 and IL-12, IL-13 in the BALF and the serum of patients with IPF. RESULTS: In
      the BALF of patients with IPF, the levels of PGE2 (591 +/- 88) ng/L and IL-13 (38
      +/- 5) ng/L were higher than that of the control group (P < 0.01), and the level
      of IL-12 (1.34 +/- 0.25) ng/L was lower than that of control group. In the
      patients with IPF, the change of IL-13 in the serum was consistent with the
      change in the BALF. But the levels of PGE2 (235 +/- 13) ng/L and IL-12 (2.35 +/-
      0.14) ng/L in the serum showed no significant difference between the patients
      with IPF and the control group. CONCLUSIONS: In the patients with IPF the
      increase of PGE2 may be correlated with the increase of IL-13 and the decrease of
      IL-12. It suggests that disequilibrium of Th1/Th2 plays an important role in the
      development of IPF. The increase of PGE2 in IPF is a local event rather than a
      systemic effect.

PMID- 15256085
TI  - [Study of the function of coagulation, fibrinolysis and pulmonary vascular
      endothelium before and after experimental pulmonary thromboembolism in rabbits].
AB  - OBJECTIVES: To study the functional changes and the significance of coagulation,
      fibrinolysis and pulmonary vascular endothelium before and after experimental
      pulmonary thromboembolism in rabbits. METHODS: Rabbit pulmonary thromboembolism
      models by injection of auto-blood clots into femoral vein were used to observe
      the dynamical changes of activity of coagulation and fibrinolysis and endothelin
      1 (ET-1), nitrogen monoxide (NO), von Willebrand factor (vWF) in blood. RESULTS:
      Petechial and patchy hemorrhages were observed on the surfaces of embolic lungs.
      The injected blood clots and secondary thrombosis in the pulmonary arteries,
      inflammatory cell infiltration around alveoli, local hemorrhages in the alveoli
      and interstitial tissue could be found by microscopy. The concentration of D
      dimer, ET-1 and vWF in blood were significantly elevated, and the tissue-type
      plasminogen activator (t-PA), NO and antithrombin III (AT-III) decreased
      significantly after embolism (P < 0.05). After administration of urokinase, the
      pathological injuries relieved, and the concentration of D-dimer was higher at 1
      h and 2 h after embolization than that before embolization (P < 0.05), and
      reduced to the level of pre- embolization at 4 h after embolization. The levels
      of t-PA, NO and AT-III after embolization were lower than those before
      embolization (P < 0.05). The level of ET-1 was higher at 2 h after embolization
      (P < 0.05) and reduced to the level of pre-embolization at 4 h. CONCLUSIONS: PTE
      has important impacts on coagulation, fibrinolysis and pulmonary vascular
      endothelial function. Thrombolysis with urokinase could keep the balance between
      coagulation and fibrinolysis and protect pulmonary vascular endothelial function.

PMID- 15256086
TI  - [The change and the clinical significance of peripheral blood Th1/Th2 cells in
      patients with pulmonary tuberculosis].
AB  - OBJECTIVE: To study the change of peripheral blood CD4+ helper T cells and T
      helper subtype I and II (Th1/Th2) in patients with pulmonary tuberculosis and to
      explore their changes during anti-tuberculosis chemotherapy. METHODS: CD4+ T
      cells from 105 patients with pulmonary tuberculosis and 25 normal controls were
      counted by Flow Cytometry. Peripheral blood cells were stimulated in vitro by
      phorbol myristate acetate (PMA) (25 ng/ml) and ionomycin (250 ng/ml). Cytokines
      were confined to the cells by using the protein transporting inhibitor containing
      monensin (2 micro mol/ml). These cells were incubated in 5% CO(2) for 4 h-4.5 h.
      The membrane and plasma of CD4+ helper T cells were marked by CD3 -PC5 + CD8 
      FITC + INF-gamma -PE/CD3 -PC5 + CD8 -FITC + IgG1 -PE, CD3 -PC5 + CD8 -FITC + IL-4
      -PE/CD3 -PC5 + CD8 -FITC + IgG1 -PE monoclonal antibodies respectively. Th1 and
      Th2 cells were counted and the ratio of Th1/Th2 cells was calculated. The levels
      of Th1 and Th2 cells in the 67 patients with pulmonary tuberculosis were detected
      at the end of intensive chemotherapy and at the sixth month of chemotherapy.
      RESULTS: (1) The levels of CD4+ T and Th1 cells in patients with tuberculosis
      were significantly lower than those of controls. Their values were (663 +/- 160)/
      microl vs (735 +/- 156)/ microl and (9.56 +/- 3.60)% vs (18.7 +/- 5.03)%
      respectively (P < 0.05). (2) The levels of CD4+ T and Th1 cells in patients with
      severe pulmonary tuberculosis were lower than those in patients with moderate or
      mild pulmonary tuberculosis. Their values were (579 +/- 120)/ microl vs (726 +/-
      166)/ microl, (684 +/- 192)/ microl and (5.43 +/- 2.33)% vs (12.2 +/- 1.81)% and
      (10.9 +/- 2.30)% respectively (P < 0.05). The level of Th2 cells was in contrast
      to Th1 cells and their values were (5.63 +/- 1.26)% vs (2.93 +/- 0.87)% and (3.22
      +/- 1.01)% (P < 0.01). (3) The level of Th1 cells increased while that of Th2
      decreased in the 61 patients who gradually recovered. (4) The level of Th2 cells
      in patients with smear positive tuberculosis was strikingly higher than that in
      patients with smear negative tuberculosis and their values were (5.20 +/- 0.97)%
      vs (2.77 +/- 1.96)% (P < 0.05). CONCLUSION: The detection of CD4+ helper T cells
      and Th1/Th2 cells in the peripheral blood cells from patients with pulmonary
      tuberculosis is useful in evaluating the state of disease and the effect of
      chemotherapy.

PMID- 15256088
TI  - [A study on the correlation between HLA-DR genes and susceptibility to pulmonary
      tuberculosis in a population of Han nationality from southern China].
AB  - OBJECTIVE: To analyze the association between HLA-DR genes and pulmonary
      tuberculosis and to explore susceptible genes associated with pulmonary
      tuberculosis in a population of Han nationality from southern China. METHODS:
      Using case-control study, we detected by polymerase chain reaction-sequence
      specific primers (PCR-SSP) technique the 23 alleles of HLA-DR gene sites in 110
      tuberculosis cases and 101 controls from Guangdong, Guangxi, Hunan, Hubei,
      Jiangxi and Fujian provinces. Gene frequency (GF) and odds ratio (OR) were
      calculated and compared. RESULTS: The frequency of DR16 allele in pulmonary
      tuberculosis cases was strikingly higher than that in the healthy controls
      (chi2=5.915, Pc< 0.05). Their GFs were 12.62% and 5.60% respectively, and the OR
      was 2.53. Significantly decreased frequency of DR1 and DR13.3 alleles in cases
      were found (chi2 values were 17.847 and 14.258 respectively, Pc < 0.01). Their
      ratios of GFs were 8.08% vs. 23.57% and 29.29% vs. 50.24%, and their ORs were
      0.26 and 0.33 respectively. CONCLUSIONS: The results suggest that DR16 allele is
      closely correlated to incidence of pulmonary tuberculosis in this population of
      Han nationality from southern China, or linked to susceptible genes which are
      functional. It is also suggested that expression of DR1 and DR13.3 alleles may be
      associated with an antagonist effect in the pathogenesis of pulmonary
      tuberculosis in this population.

PMID- 15256089
TI  - [Polymorphism of regulated upon activation, normal T cell expressed and secreted
      promoter region -28 position in Chinese allergic asthmatic children].
AB  - OBJECTIVE: To study the effect of regulated upon activation, normal T cell
      expressed and secreted (RANTES)-28 polymorphism on allergic asthma in Chinese
      children. METHODS: Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to identify the polymorphism at position -28 of
      the RANTES promoter in 100 asthmatic children (group A). Levels of plasma IgE and
      RANTES were detected by chemiluminescence and ELISA respectively. The number of
      peripheral eosinophils was counted. Data were compared with those of the control
      group of 90 healthy children (group B). RESULTS: (1) Both C allele and G allele
      were detected at -28 of the RANTES promoter; the prevalence of the G allele in
      group A was 19.5%, as compared to 10.6% in group B; the prevalence of RANTES-28G
      allele was significantly different between the two groups (P < 0.05). (2) For
      genotypes C/C, C/G and G/G in asthmatics, levels of plasma RANTES were (289 +/-
      199) ng/L, (515 +/- 119) ng/L and (1 071 +/- 138) ng/L, respectively, the
      difference being significant among the three genotypes (P < 0.01). (3) For
      genotypes C/C, C/G and G/G in asthmatics, total levels of plasma IgE (lg IgE)
      were 2.45 +/- 0.12, 2.77 +/- 0.07 and 3.16 +/- 0.09, respectively, the difference
      being not significant among the three genotypes (P > 0.05). (4) The numbers of
      peripheral eosinophils were (2.9 +/- 1.4) x 10(8)/L, (6.4 +/- 0.8) x 10(8)/L and
      (9.9 +/- 2.3) x 10(8)/L in genotypes C/C, C/G and G/G in asthmatics respectively,
      and the difference being significant among the three genotypes (P < 0.01).
      CONCLUSION: Polymorphism of RANTES C-28G was associated with susceptibility of
      asthma in children, and may aggravate the disease through increasing the level of
      RANTES and eosinophils.

PMID- 15256090
TI  - [Imbalanced T cell-specific transcription factors T-bet and GATA-3 contributes to
      type 2 T helper cell polarization in asthmatic patients].
AB  - OBJECTIVE: To identify the T helper cell predominant differentiation in asthmatic
      patients and to explore the modulation of T cell-specific transcription factors T
      bet/GATA-3. METHODS: Thirty-two asthmatic patients were enrolled, among whom 18
      were atopic defined by positive antigen skin test and 12 were children.
      Lymphocytes were isolated from peripheral blood and incubated with PHA (100
      microg/ml) at 37 degrees C for 48 hours. INF-gamma and IL-4 concentrations in the
      supernatant were detected by ELISA. The T-bet and GATA-3 mRNA expression levels
      in lymphocytes were assayed by reverse transcription-polymerase chain reaction
      (RT-PCR) while the ratio of CCR3+ and CCR5+ cells in lymphocytes was counted by
      flow cytometry (FCM) after direct immunofluorescence staining. RESULTS: IL-4
      concentration in the lymphocyte supernatant of the asthmatic group was (118 +/-
      25) microg/L, which was significantly elevated compared to that of the healthy
      control group (75 +/- 12) microg/L (P < 0.01). When subgroups of asthmatic
      patients were compared, the results showed that atopic subjects had a higher IL-4
      level than non-atopic subjects [(126 +/- 23) microg/L vs (107 +/- 26) microg/L, P
      < 0.01], but no significant difference was demonstrated between adults and
      children [(118 +/- 25) micro g/L vs (121 +/- 25) microg/L, P > 0.05].
      Significantly lower concentration of INF-gamma in the asthmatic group was
      detected as compared to the control [(651 +/- 85) microg/L vs (1 179 +/- 332)
      microg/L, P < 0.001]. The concentration of INF-gamma was higher in atopic
      subjects than in non-atopic subjects [(618 +/- 89) micro g/L vs (680 +/- 83)
      microg/L, P < 0.01], but no difference was found between adults and children. The
      percentage of CCR3+ cells in lymphocytes was (9.4 +/- 5.8)% in the asthmatic
      group and (4.9 +/- 2.3)% in the control (P < 0.05), while the percentages of
      CCR5+ cells was (6 +/- 7)% and (13 +/- 7)%, respectively (P < 0.05). RT-PCR
      revealed that T-bet mRNA expression levels were as follows: 0.13 +/- 0.03 in the
      asthmatic group and 0.18 +/- 0.04 in the control (P < 0.01); 0.120 +/- 0.030 in
      atopic subjects and 0.140 +/- 0.010 in the non-atopic subjects (P < 0.05); 0.120
      +/- 0.020 in children and 0.130 +/- 0.020 in adults (P > 0.05). The levels of
      GATA-3 mRNA expression were 0.43 +/- 0.07 in asthma and 0.29 +/- 0.09 in the
      control (P < 0.01), however, no differences were found between atopic and non
      atopic, children and adults (0.50 +/- 0.12 vs 0.40 +/- 0.10, 0.44 +/- 0.09 vs
      0.43 +/- 0.07, respectively, P > 0.05). A positive correlation was found between
      concentration of INF-gamma and T-bet mRNA level (r=0.663, P < 0.01), while no
      correlation with GATA-3 mRNA expression was found. The concentration of IL-4 was
      negatively correlated with T-bet mRNA level (r=-0.250, P < 0.05) and positively
      with GATA-3 mRNA level (r=0.72, P < 0.01). It was interesting that a closer
      relationship existed between the ratio of T-bet to GATA-3 and the ratio of INF
      gamma to IL-4 (r=0.873, P < 0.01). CONCLUSIONS: In asthma there is a tendency of
      Th2 polarization with over-production of Th2-like cytokines in which T-bet
      deficiency may be a key factor. T-bet might direct T cells to Th1 differentiation
      while GATA-3 orientated Th2 maturation. Considering the fact that committed Th2
      cells underwent re-differentiation induced by T-bet, this novel Th1-specific
      transcription factor is a fascinating target gene for modifying to restore the
      Th1 and Th2 balance.

PMID- 15256091
TI  - [A study on the active efflux mechanism in Staphylococcus aureus resistant to
      quinolone].
AB  - OBJECTIVE: To explore the effect, the characteristic, and potential approaches to
      the active efflux mechanism in straphylococcus aureus (S. a) resistant to
      quinolones. METHODS: S. a standard strain ATCC25923 and clinical isolates
      susceptible to quinolone were inoculated onto MH agar containing ofloxacin at a
      concentration of 4 x MIC (in the presence or absence of 20 micro g of
      reserpine/ml). Following incubation at 35 degrees C for 48 h, the inhibiting
      effect of reserpine on the occurrence of induced resistance was observed and the
      MIC of the induced resistant strain to ethidium bromide (EB), ofloxacin and
      ciprofloxacin (in the presence or absence of 20 micro g of reserpine/ml) was
      determined. The influence of reserpine to the MIC of induced resistant strains
      was also determined. The accumulation and loss of EB was determined based on the
      fact that EB's fluorescence can be strengthened when combined with DNA. Reserpine
      inhibition test was used to study the active efflux in clinical S. a resistant to
      quinolone. RESULTS: The active efflux mechanism in S. a resistant to second
      generation quinolones was confirmed by the reserpine's influence on the level of
      ethidium bromide (EB) in the cytoplasm of S. a. Reserpine reduced the 50 percent
      resistant rate to quinolone in induced resistant S. a, and decreased the MIC of
      induced resistant strains. Reserpine inhibited the active efflux of EB from the
      cytoplasm of S. a. CONCLUSIONS: Active efflux is an important mechanism in S. a
      resistant to quinolone. Reserpine can inhibit its active efflux mechanism, and
      has synergistic effect with quinolone, which hold therapeutic potential for S. a
      resistant to quinolones.

PMID- 15256103
TI  - [Inhalation chemotherapy for metastatic cancer in the lung].

PMID- 15256104
TI  - [Advances in gene therapy for lung cancer].

PMID- 15256105
TI  - [The advances of histopathology and molecular pathology of endocrine tumors].

PMID- 15256106
TI  - [4th National conference on pathological diagnosis, endocrine tumor pathology and
      pathology of SARS].

PMID- 15256107
TI  - [Distinction between benign and malignant pheochromocytomas].
AB  - OBJECTIVES: To investigate the differences in morphology, immunohistochemistry,
      DNA ploidy status, LOH and MSI of 11q13 and 1p between benign and malignant
      pheochromocytomas, and to find the marker or markers useful in distinction
      between benign and malignant pheochromocytoma or for predicting the malignant
      potential of this tumor. METHODS: Twenty-two cases of clinically documented
      benign and malignant pheochromocytomas from the files of Peking Union Medical
      College Hospital were analyzed. Aside from histological study, Ki-67, p53, CgA, S
      100, PCNA and survivin immunohistochemistry studies were performed. DNA ploidy
      status was assessed by flow cytometry on cell suspensions prepared from formalin
      fixed, paraffin-embedded sections. Twelve tumors (7 benign and 5 malignant) with
      paired normal tissues were microdissected. Tumor and normal tissue DNA were
      extracted. The obtained DNAs and 8 microsatellite markers related to 11q13 and 1q
      were subjected to PCR amplification for analysis of LOH and MSI. RESULTS: None of
      the tumors showed atypical mitosis, only 1 malignant tumor had a mitotic count >
      1/10 HPF (2.3/10 HPF). Two malignant tumors exhibited confluent necrosis. Ki-67
      index was low in benign tumors (average 0.73%), and high in malignant tumors
      (average 2.4%). The difference of Ki-67 index between benign and malignant tumors
      was statistically significant. DNA ploidy status did not correlate with
      malignancy. Although LOH and/or MSI of 11q13 and 1p were observed in several
      tumors, a statistically significant difference could not be reached due to the
      small number of tumors analyzed. CONCLUSION: Only Ki-67 index (> 3%) is an useful
      marker for distinguishing benign from malignant or for predicting the malignant
      potential of pheochromocytoma.

PMID- 15256109
TI  - [Thyrotropin-secreting pituitary adenoma:a clinicopathological analysis of seven
      cases].
AB  - OBJECTIVE: To study the clinicopathological features of thyrotropin-secreting
      pituitary adenoma (TSH adenoma). METHODS: Clinical and pathological features of 7
      TSH adenoma cases were studied by review of patients' medical records, light and
      electronic microscopy, and immunohistochemistry. RESULTS: All seven patients
      presented with clinical hyperthyroidism and high levels of plasma free T3, free
      T4, total T3 and total T4. The levels of TSH failed to be suppressed by thyroxin
      administration. MRI showed macro or giant pituitary adenomas in all seven
      patients with tumor diameters ranging from 2.0 to 5.0 cm. Under light microscope,
      there were 5 cases of chromophobe cell adenoma, 1 case of acidophil cell adenoma,
      and 1 case of mixed acidophil and chromophobe cell adenoma. Immunohistochemical
      stains showed a strong positivity of TSH in all the tumors, PRL positive cells in
      1 tumor, GH positive cells in 2 tumors and scattered GH and PRL double positive
      cells in 3 tumors. Ki-67 proliferation index ranged from 0 approximately 0.4%.
      P53 immunostain was negative in all tumors. After initial surgery, 2 cases had
      recurrences. However, the Ki-67 proliferation index was not elevated in these two
      tumors. CONCLUSIONS: The histological features of TSH pituitary adenomas are
      heterogeneous with chromophobe as the most common subtype. Secretion of TSH was
      detected by immunohistochemistry in all cases. P53 mutation is not a feature of
      TSH adenoma and the proliferation marker, such as Ki-67, may not predict clinical
      behavior of the tumor. Recurrence is likely due to incomplete resection.

PMID- 15256108
TI  - [Diagnostic value of A103 and inhibin-alpha in adrenocortical tumors: an
      immunohistochemical study using tissue microarray techniques].
AB  - OBJECTIVE: To investigate the potential diagnostic value of A103 and inhibin
      alpha in adrenocortical tumors and to evaluate the applicability of tissue
      microarray/tissue chip in pathological studies using immunohistochemistry.
      METHODS: A tissue microarray/tissue chip was constructed to contain 179 formalin
      fixed, paraffin-embedded adrenal tissue samples which include 3 normal adrenal
      cortex, 2 fetal adrenal cortex, 2 nodular adrenocortical hyperplasia samples, 72
      adrenocortical adenomas, 39 adrenocortical carcinomas, 3 adrenal medulla, 13
      metastatic carcinomas, 4 metastatic malignant melanomas and 44 pheochromocytomas.
      Additional 20 cases of normal adult adrenal gland were used as controls.
      Immunohistochemical markers, including A103, inhibin-alpha, calretinin and Ki-67
      were used on the tissue array sections by EnVision immunohistochemical staining
      methods. RESULTS: Positive staining of A103 was seen in all of the 23 (100%)
      adrenal cortex, 2 fetal adrenal cortex, 2 nodular adrenocortical hyperplasia
      samples, 60 of 66 (90.9%) adrenocortical adenomas samples, 35 of 37 (94.6%)
      adrenocortical carcinomas samples, 3 of 3 malignant melanomas, but in none of the
      adrenal medulla, pheochromocytomas or adrenal metastatic carcinoma samples. In
      all of the adrenal cortex, fetal adrenal cortex and nodular adrenocortical
      hyperplasia cases, inhibin-alpha immunoreactivity was limited to the zona
      reticularis and the innermost zona fasciculata. Fifty of the 66 (75.8%)
      adrenocortical adenomas, 28 of the 37 (75.7%) adrenocortical carcinomas were
      positive for inhibin-alpha. None of the adrenal medulla, pheochromocytoma,
      metastatic malignant melanoma or carcinoma samples showed a positive inhibin
      alpha immunostain. CONCLUSIONS: The tissue microarray/tissue chip technique
      provides a reliable method to investigate marker expression by offering a rapid,
      economic and accurate screening of tissue specimens on a large scale. The
      combined use of A103 and inhibin-alpha is valuable in distinguishing
      adrenocortical tumor from pheochromocytoma and other metastatic neoplasms.

PMID- 15256110
TI  - [Expression of cytokeratin19, galectin-3 and HBME-1 in thyroid lesions and their
      differential diagnoses].
AB  - OBJECTIVE: To study immunohistochemical expression of cytokeratin19 (CK19),
      galectin-3 (Gal-3) and HBME-1 in thyroid lesions and to assess their usefulness
      as markers in the differential diagnoses of thyroid nodular lesions. METHODS:
      Immunohistochemical staining was performed on formalin-fixed paraffin-embedded
      tissue of 21 cases of nodular goiters, 14 cases of toxic goiters, 15 cases of
      follicular adenomas (FA), 13 cases of follicular carcinomas (FC), 13 cases of
      follicular variant papillary carcinomas (FVPC) and 48 cases of classic papillary
      carcinomas (CPC). RESULTS: All three markers were expressed in the cytoplasm with
      no or weak expression in benign lesions and diffuse and strong in malignant
      cases. Positive expressions of CK19, Gal-3 and HBME-1 were present in 11of 21,
      two of 21, four of 21 in nodular goiters, seven of 14, one of 14, one of 14 in
      toxic goiters, nine of 15, two of 15, two of 15 in FA, 10 of 13, eight of 13,
      seven of 13 in FC, 13 of 13, 11 of 13, 12 of 13 in FVPC, and 48 of 48, 45 of 48,
      46 of 48 in CPC. The expression rates of the three markers between benign lesions
      (nodular goiters, toxic goiters and FA) and malignant lesions (FA, FVPC and CPC)
      were statistically significant. Among the three follicular lesions (FA, FC and
      FVPC), the differences were statistically significant as well. Nine, seven and
      six cases were negative for all three markers in nodular goiters, toxic goiters
      and FA, respectively. Only one case in FC was negative for all three markers, no
      case was all negative in FVPC and CPC; the rate of one case with two or more
      positive marker expression in nodular goiters, toxic goiters, FA, FC, FVPC and PC
      was 14.2% (3/21), 21.43% (3/14), 20.0% (3/15), 69.2% (9/13), 92.3% (12/13),
      100.0% (48/48), the differences between benign lesions and malignant lesions and
      between FA, FC and FVPC were also statistically significant. CONCLUSIONS:
      Immunohistochemical stains of CK19, Gal-3 and HBME-1, especially when used in
      combination, can be an important adjunct to the histopathological diagnoses of
      thyroid lesions.

PMID- 15256111
TI  - [Ovarian tumors with endocrine function].
AB  - OBJECTIVE: To analyze the clinicopathological features of ovarian tumors with
      endocrine function. METHODS: Twenty-four cases of ovarian tumor with endocrine
      manifestation were collected from the hospital. Their clinical presentation and
      histopathologic features were reviewed, along with a panel immunohistochemistry
      stainings (EnVision method). The antibodies were AE1/AE3, epithelial membrane
      antibody (EMA), alpha-inhibin, calretini and smooth myoglobin (SMA). RESULTS: The
      main clinical endocrinological manifestations were related to an excess
      production of sex steroids. Histologically, the principle histological subtype of
      these tumors was ovarian sex cord-stroma tumors, including 13 cases ovarian type
      (8 granulosa cell tumors, 2 thecofibromas, 3 sclerosing stromal tumors), 7 cases
      testicular type (1 sertoli cell tumors, 5 sertoli-Leydig cell tumors, 1 Leydig
      cell tumor, and 2 cases of steroid cell tumor (NOS). Another 2 cases were ovarian
      epithelial tumors. Grossly, 50% (11/22) ovarian sex cord-stromal tumors were less
      than 5 cm in diameter. However, 4 tumors were quite larger, up to 18 cm in
      diameter. Most of these tumors were solid or solid-cystic and their cut surfaces
      were brown, pink, yellow or grey in color. The 2 primary ovarian epithelial
      tumors were larger, being 12 cm and 14 cm in diameter, respectively.
      Immunohistochemically, ovarian sex cord-stromal tumors showed positive staining
      for alpha-inhibin in all cases (22/22) and for calretinin in majority cases
      (18/22), and that the intensity of reactivity correlated with the degree of tumor
      differentiation. The non-neoplastic, luteinized stromal cells in 2 ovarian
      primary epithelial tumors also showed positive staining. Five cases of
      fibrothecomas and sclerosing stroma tumors were all positive for SMA. Although 6
      of the 22 ovarian sex cord-stromal tumors were AE1/AE3 positive, all were EMA
      negative. CONCLUSIONS: Most endocrinological syndromes in ovarian neoplasia
      reflect an overproduction of sex steroids, but the clinical manifestations do not
      correlate with the tumor histological subtypes. Most functional ovarian tumors
      are sex cord-stromal tumors and are usually of small to medium in size, but few
      are larger or giant. The size of the tumor does not correlate with the duration
      and the degree of clinical manifestations. Ovarian tumors of non-sex cord-stromal
      type may also be clinically functional. The immunohistochemical results suggests
      that alpha-inhibin and/or calretinin expression are useful markers in support of
      a diagnosis of sex cord-stromal tumor of the ovary. Although some of these tumors
      are AE1/AE3 positive, EMA negativity may be useful for the differential diagnosis
      with epithelial ovarian tumors.

PMID- 15256112
TI  - [Clinicopathological characteristics of atypical cystic duct (ACD) of the breast:
      assessment of ACD as a precancerous lesion].
AB  - OBJECTIVE: To assess the clinicopathological features of atypical cystic duct
      (ACD) as a precancerous lesion of the breast. METHODS: Whole mammary gland serial
      sections were performed on 200 cases of breast cancer without pre-operative
      biopsy (prior operation, fine needle aspiration or needle biopsy were routinely
      performed in each case). The clinicopathological findings and immunohistochemical
      features of ACD were investigated. RESULTS: Forty-four (22%) of the 200 breast
      cancer patients had ACD breast lesions. The frequency of patients with ACD
      increased in premenopausal women (P=0.001). A number of ACD lesions displayed a
      histological transition to adjacent ductal carcinoma in-situ. In 16 of 44 (36%)
      patients with ACD, carcinoma cells stained positive for p53. In 12 of these 16
      cases (75%), ACD cells also stained positive for p53 protein (P=0.001).
      Myoepithelial cells of ACD appeared attenuated and stained strongly for alpha
      smooth muscle actin. There was no correlation between the ACD-present group and
      the ACD-absent group in tumor size, nodal metastasis, and immunostaining patterns
      of estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2 and Ki-67
      labeling index of cancerous tissues. All 44 ACD lesions showed a negative
      staining of c-erbB-2, regardless of the staining result in their corresponding
      carcinomas. The mean Ki-67 labeling index of ACD lesions was low. CONCLUSIONS:
      ACD is frequently associated with breast cancer. It may represent a precancerous
      mammary lesion, supported by the frequent histological continuum between ACD and
      malignancy, and simultaneous p53 over-expression present in both ACD and its
      corresponding breast carcinoma.

PMID- 15256114
TI  - [Thirty base pair (30 bp) deletion in latent membrane protein 1 oncogene in
      lymphoepithelial carcinoma of salivary glands].
AB  - OBJECTIVE: To investigate 30 bp deletion of latent membrane protein (LMP)-1 gene
      in lymphoepithelial carcinoma (LEC) of the salivary glands and to determine the
      frequency of this deletion. METHODS: Forty-six cases of salivary gland LEC were
      investigated by PCR to explore the site specific, 30 bp deletion in the 3'
      terminal region of LMP-1 gene. To guarantee amplifiable DNA extracted from
      paraffin-embedded tissue sections, PCR amplification of a house-keeping gene
      (beta-actin) was performed simultaneously. In addition, DNA sequencing of the PCR
      product was performed in representative cases. RESULTS: Although amplifiable DNA
      was obtained in 42 of the 46 specimens, as indicated by beta-actin gene
      amplification, successful amplification of LMP-1 gene was achieved in 35/42
      (83.3%) cases. Two types of PCR products of LMP-1 gene were observed and
      confirmed by DNA sequencing. A wild-type PCR product (316 bp) was present in 31
      cases (88.6%) and only 4 cases (11.4%) showed an aberrant 286 bp PCR product,
      corresponding to the 3' terminal 30 bp deletion of the gene. CONCLUSION: Site
      specific 30 bp deletion of LMP-1 gene is not a common feature of salivary gland
      LEC.

PMID- 15256113
TI  - [Clinicopathological study of 145 childhood rhabdomyosarcoma cases].
AB  - OBJECTIVE: To study the clinicopathological, immunohistochemical and electron
      microscopic characteristics of pediatric rhabdomyosarcomas (RMS). METHODS: One
      hundred and forty-five cases of pediatric rhabdomyosarcomas were studied by
      routine histological, immunohistochemical and electron microscopic studies.
      RESULTS: There were 97 male and 48 female patients with ages ranging from 4
      months to 13 years and a mean of 4.2 years. The follow-up period of 100 patients
      was from 1 year to 20 years with a mean of 5 years after diagnosis. All cases
      were subtyped into the following histological categories: embryonal RMS, botryoid
      RMS, spindle cell RMS, alveolar RMS and solid RMS. Histopathological subtypes,
      tumor site and tumor stage correlated significantly with the patients' 5 years
      survival. The best prognosis was observed in spindle cell and botryoid RMS.
      Embryonal RMS carried an intermediate prognosis. Patients with alveolar RMS and
      solid RMS had the worst prognosis. Tumors involving bladder, head and neck
      carried a favorable clinical outcome. Patients with tumors involving trunk 
      extremities  retroperitoneum and pelvis did poorly. Immunohistochemically, all
      cases were positive for Vimentin. The positive staining rates for desmin, SMA and
      myoglobin were 78%, 75% and 37%, respectively. All tumors were negative for NSE,
      CD99 and LCA. Electron microscopy study showed features of myofilament and
      sarcomere in 10 of 15 cases. CONCLUSIONS: RMS is the most common soft tissue
      sarcoma of childhood. Immunohistochemistry and electron microscopy are helpful in
      diagnosis and classification of RMS.

PMID- 15256115
TI  - [Detection of API2-MALT1 fusion gene transcript and its diagnostic value in
      pulmonary MALT lymphoma].
AB  - OBJECTIVE: To investigate the feasibility of detecting API2-MALT1 fusion gene
      transcript in paraffin-embedded tissue and its diagnostic value for pulmonary
      MALT lymphoma. METHODS: Ten archival cases of pulmonary MALT lymphoma were
      selected and reviewed. Five archival cases of chronic lymphadenitis were used as
      negative control. Detection of the API2-MALT1 fusion transcript was performed by
      RT-PCR followed by second-round PCR using nested primers. beta-actin mRNA assay
      was utilized as an internal control in all samples. RESULT: beta-actin was
      detected in all samples (100%). The API2-MALT1 fusion transcript was found in 3
      of 10 pulmonary MALT lymphomas (30%) and in none of the 5 chronic lymphadenitis
      cases. The pulmonary lesions in the fusion gene positive cases were all single
      tumors of less than 5.0 cm in diameter and limited to either the right or left of
      the lung. CONCLUSION: Detection of API2-MALT1 fusion transcript in paraffin
      embedded tissues is feasible by nested RT-PCR and is of diagnostic value. The
      presence of API2-MALT1 fusion gene may be correlated with a subset of pulmonary
      MALT lymphomas that have limited lung involvement.

PMID- 15256117
TI  - [Expression and pathobiological implication of hypoxia-inducible factor-1alpha in
      human colorectal carcinoma].
AB  - OBJECTIVE: To investigate the transcription level and protein expression of HIF
      1alpha and VEGF in SW480 cell line and colorectal adenocarcinoma, and to
      determine whether HIF-1alpha plays a role in angiogenesis through its regulation
      of VEGF. METHODS: HIF-1alpha mRNA expression was analyzed by in situ
      hybridization. HIF-1alpha and VEGF protein expressions were determined by
      immunochemical streptavidin/peroxidase (SP) in SW480 cells and colorectal
      carcinoma tissue samples and Western blot, using proteins extracted from SW480
      cells. Tumor tissue microvessel density (MVD) was determined by CD34
      immunostaining of colorectal carcinomas. RESULTS: The levels of HIF-1alpha mRNA
      changed significantly in response to different oxygen concentrations and an
      addition of genistein in SW480 cells. Immunocytochemistry revealed that the
      levels of HIF-1alpha, VEGF protein expression in SW480 cells were significantly
      higher under hypoxia than those in nomoxia (P < 0.01, P < 0.05 respectively).
      However, addition of genistein, an inhibitor of HIF-1alpha, suppressed such
      responses to hypoxia. Western blot analysis showed that SW480 cells exposed to
      hypoxia expressed a high level of HIF-1alpha protein, compared to a weak
      expression in nomoxia. The addition of genistein in hypoxia suppressed the over
      expression of HIF-1alpha. The positive rates of HIF-1alpha mRNA by in situ
      hybridization in colorectal adenomas and adenocarcinomas were 38.9% (7/18) and
      67.7% (42/62), respectively. The percentage of HIF-1alpha mRNA positive cells
      varied significantly from colorectal adenomas to adenocarcinomas at different
      Duke stages (P < 0.05), and HIF-1alpha mRNA was higher in adenocarcinomas than in
      adenomas (P < 0.01). The positive rates of HIF-1alpha and VEGF protein expression
      in adenocarcinomas were 43.5% (27/62) and 37.1% (23/62), respectively. The
      expression of VEGF elevated as the Duke tumor staging increased. The conformation
      rate of HIF-1alpha and VEGF was 74.2% (46/62). MVD was significantly higher in
      HIF-1alpha and/or VEGF positive tumors than those without (P < 0.01 and P < 0.05
      respectively). Among the four groups, i.e. HIF-1alpha+/VEGF+, HIF-1alpha+/VEGF-,
      HIF-1alpha+/VEGF- and HIF-1alpha-/VEGF-, the difference of MVD was highly
      significant (P < 0.01). HIF-1alpha expression was correlated significantly with
      VEGF expression and microvessel density. CONCLUSIONS: These findings suggest
      hypoxia induces the expression of HIF-1alpha and VEGF in colorectal
      adenocarcinoma. HIF-1alpha may play an important role in angiogenesis and tumor
      progression by regulating the expression of VEGF in human colorectal carcinoma.

PMID- 15256116
TI  - [Study of mutations in 5'-noncoding region of BCL-6 gene in B-cell non-Hodgkin's
      lymphomas].
AB  - OBJECTIVE: To investigate BCL-6 gene mutations in B-cell non-Hodgkin lymphomas (B
      NHL) and their implications in lymphoma pathogenesis. METHODS: Polymerase chain
      reaction (PCR) and direct DNA sequencing methods were used to identify mutations
      in the 5'-noncoding region of BCL-6 gene in 135 cases of B-NHL, 5 cases of T-NHL,
      5 cases of nodular lymphocyte predominance Hodgkin's lymphoma (NLPHL) and 10
      cases of reactive hyperplasia of lymph node. RESULTS: Mutations were identified
      in 6 cases of nodal DLBCL (27.3%), 4 cases of FL (22.2%), 4 cases of MALT
      lymphoma (22.2%), 4 cases of extranodal DLBCL (20.7%) and 2 cases of LRH (20%).
      No mutations were detected in T-NHL and NLPHL (P < 0.05). There were no
      significant differences in incidences of BCL-6 gene mutations between nodal and
      extranodal DLBCL (P > 0.05). All mutations were base substitutions and the
      frequency of single-base change was 0.14 x 10(-2)/bp approximately 0.68 x 10(
      2)/bp. CONCLUSIONS: Mutations of the 5'non-coding region of BCL-6 gene may be
      involved in the pathogenesis and progression of B-NHL. Molecular demonstration of
      such mutations may provide a marker of lymphomas derived from the germinal center
      related B cells.

PMID- 15256118
TI  - [Growth suppression of colon cancer cells in vitro by DPC4 gene expression and
      its mechanism].
AB  - OBJECTIVE: To study the effect of DPC4 gene expression on the growth of colon
      cancer cells and its mechanism. METHODS: Expression plasmid pcDNA3.1-DPC4 was
      constructed and transfected into the colon cancer cell line SW620 by use of
      lipofectamine gene transfer technique. DPC4 protein expression was detected by
      Western blot and immunocytochemistry. The effect of DPC4 gene on the growth of
      SW620 cells was monitored by population doubling time (PDT) and cloning
      efficiency. The influence of DPC4 expression on p21WAF1 transcription was
      investigated by RT-PCR to detect p21WAF1 mRNA. RESULTS: Successful expression of
      DPC4 protein was detected in the transfected SW620 cells. Compared with the
      control cells, PDT (74 h) of the DPC4 expressing cells was prolonged and the
      cloning efficiency (21%) decreased. In addition, the mRNA level of p21(WAF1) in
      DPC4 transfected cells was increased. CONCLUSIONS: Overexpression of DPC4 gene
      inhibits the growth of colon cancer in vitro, and induction of p21(WAF1)
      expression may be an important functional aspect of DPC4.

PMID- 15256119
TI  - [Reversal of multidrug resistance of tumor cells by anti-mdr1 ribozyme].
AB  - OBJECTIVE: To stably reverse the multidrug resistance (MDR) of breast carcinoma
      cells in vitro. METHODS: Two anti-mdr-1 ribozyme plasmids, RZ196 and RZ179, were
      constructed with EGFP as reporter gene and transfected into drug-resistant breast
      carcinoma cells in vitro. The expression of EGFP was observed by laser confocal
      microscopy. Flow cytometry, RT-PCR and Rhodamine123 efflux assay were used to
      detect P-glyco protein (p-gp) and mdr-1 mRNA. RESULTS: After transfection with
      RZ196 and RZ179, the mdr-1 indices were reduced from 2.20 to 0.76 and 1.40, the
      expression rates of p-gp were reduced from 55.0% to 4.6% and 18.2%, the
      fluorescence intensity increased from 22.0% to 46.2% and 70.1%, TCL reduced from
      75% to 28% and 43% respectively. In addition, the expression of ribozyme plasmid
      in tumor cells was stable under G418 selection. After two months, the mdr-1
      indices remained at 0.81 and 1.47 in the cells transfected RZ196 and RZ179
      respectively. The expression rates of p-gp were 5.2% and 19.5% and the Rh123
      fluorescence intensity was 51.4% and 71.6% respectively. CONCLUSIONS: Both anti
      mdr-1 ribozyme RZ196 and RZ179 can stably reverse MDR phenotype of breast
      carcinoma cells in vitro. RZ196 construct appears to be more effective.

PMID- 15256120
TI  - [Effect of nylestriol on bone remodeling in ovariectomized rats].
AB  - OBJECTIVE: To clarify the effects of nylestriol on microarchitecture and
      interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats.
      METHODS: 30 female rats were randomly allocated into 3 groups: sham, OVX and
      nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed
      with nylestriol for 3 months and the bone mineral density (BMD) was measured in
      lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the
      animal, bone histomorphometric parameters were measured to study the changes in
      bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6
      mRNA in bone tissue. RESULTS: BMD was significantly reduced, while IL-6 mRNA
      level elevated in the OVX group compared with the sham group. Static
      histomorphometric data showed that the trabecular bone volume, mean trabecular
      plate thickness and density were reduced while the mean trabecular plate space
      elevated remarkably in the OVX group in comparison with that in the sham group.
      As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled
      surface and bone turnover rate were increased while osteoid maturation rate
      decreased significantly in the OVX group compared with the sham group. BMD, IL-6
      mRNA expression and bone histomorphometric parameters were improved in nylestriol
      treated rats. CONCLUSION: Nylestriol plays an important role in maintaining bone
      volume and improving bone microarchitecture by markedly inhibiting bone turnover
      and bone resorption, which might be to some degree attributed to reduced IL-6
      expression.

PMID- 15256121
TI  - [Paratesticular embryonal rhabdomyosarcoma-- a case report].

PMID- 15256122
TI  - [Experimental lung carcinogenic in vivo study of aflatoxin G1 in NIH mice].
AB  - OBJECTIVE: Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family
      produced by aspergillus flavus. It is a major contaminating mycotoxin in food in
      areas of China with high cancer incidence. The purpose of this study is to
      explore the carcinogenic effects of AFG1 in NIH mice. METHODS: NIH mice were
      randomly divided into three groups. Two experimental groups were treated
      intragastrically by gavage with AFG1 3 microg/kg and AFG1 30 microg/kg
      respectively, 3 times a week for 24 weeks. The control group was treated with
      normal saline. All mice were fed with food that was free of AFGs as confirmed by
      HPLC analysis. The mice were weighed every week throughout the entire experiment,
      and then sacrificed and examined pathologically at the 58th and 74th weeks
      respectively. RESULTS: Compared with control mice receiving no AFG1, bronchial
      epithelial hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were
      observed in mice receiving AFG1 treatment. The incidences of bronchial epithelial
      hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were 60.0%, 10.0%
      and 30.0% for mice receiving 3 microg/kg AFG1 and 28.6%, 35.7%, 42.9% for mice
      receiving 30 microg/kg of the toxin, respectively. CONCLUSION: Oral
      administration of AFG1 can induce hyperplastic lesions and adenocarcinoma of lung
      in NIH mice.

PMID- 15256123
TI  - [ Lymphatic metastasis polymorphic adenoid Melanoma, Amelanotic--a case report].

PMID- 15256124
TI  - [Expression of NDRG1 gene in the progression of colorectal cancer and its
      relation to lymphatic metastasis].

PMID- 15256125
TI  - [Pathology of cervix blue nevus].

PMID- 15256127
TI  - [The advances of molecular pathology of follicular thyroid carcinoma].

PMID- 15256131
TI  - [Beta-catenin-accumulated crypt--a novel pre-cancerous condition in rat
      colorectal neoplasm model].

PMID- 15256132
TI  - [Milestone bring forth new idea on pathological laboratory].

PMID- 15256137
TI  - [Primary cardiac malignant tumor--report of 6 cases].

PMID- 15256138
TI  - [Left atrial malignant mesenchymoma--a case report].

PMID- 15256139
TI  - [Diffuse malignant deciduoid peritoneal mesothelioma--a case report].

PMID- 15256140
TI  - [Extraskeletal myxoid chondrosarcoma--a case report].

PMID- 15256141
TI  - [Ovarian Sertoli-leydig cell tumor--a case report].

PMID- 15256142
TI  - [Huge right ventricular fetal type rhabdomyoma in infant--a case report].

PMID- 15256143
TI  - [Pathological diagnosis of colorectal neoplasm and precancerous condition with
      biopsy of the lesion].

PMID- 15256144
TI  - [Apoptosis induced by hydroquinone in bone marrow mononuclear cells in vitro].
AB  - OBJECTIVE: To study the effect of hydroquinone on apoptosis of bone marrow
      mononuclear cells, and to evaluate the toxic effect of benzene on stem cells.
      METHODS: Cell morphology was observed by HT fluorescent stain method, and DNA
      fragments were analyzed by agarose gel electrophoresis. Anti-Annexin V FITC plus
      PI staining for apoptotic and necrotic rate was examined by flow cytometer.
      RESULTS: After adding different concentrations of hydroquinone to the cells for 6
      h culture, the fluorescent intensity of nucleus increased, the color of nucleus
      became deep and inhomogeneous, and the chromatin was condensed and distributed
      around the neucleus. DNA ladder was detected in all samples. Cell apoptotic rate
      in different concentration of hydroquinone groups was significantly higher than
      that in blank control group (P < 0.05). With the increase of the concentration of
      hydroquinone, the apoptotic and necrotic rate also increased. The optimal
      concentration of hydroquinone was 50 micro mol/L. When it was >or= 75 micro
      mol/L, the necrotic rate increased significantly. Hydroquinone-induced apoptosis
      was associated with culture time at the concentration of 50 micro mol/L, and the
      peak apoptotic time was 10 h, then the apoptotic rate decreased and necrotic rate
      increased. CONCLUSION: Hydroquinone can induce apoptosis of bone marrow
      mononuclear cells in vitro with dose-effect and time-effect relationship.

PMID- 15256145
TI  - [The protective effect of amifostine on hydroquinone-induced apoptosis in bone
      marrow].
AB  - OBJECTIVE: To evaluate the protective effect of amifostine on hydroquinone
      induced apoptosis of bone marrow mononuclear cells in vitro. METHODS: The
      mononuclear cells were separated and divided into four groups: blank control,
      amifostine group, hydroquinone group, amifostine + hydroquinone group. The cell
      apoptotic rate was examined in separated group at different time point, and
      apoptosis was detected by HT stain, then cell morphology was observed under
      fluorescent microscope and DNA fragments was tested by agarose gel
      electrophoresis. In addition, apoptotic and necrotic rate was detected by flow
      cytometer. RESULTS: After 10 hour culture, DNA ladder was detected in the
      hydroquinone group, but not in other groups. The apoptotic rate was not
      significantly different between amifostine group and blank control group at
      different culture time (P > 0.05). After 8 - 12 hour culture, the apoptotic rate
      in amifostine + hydroquinone group was significantly lower than that in the group
      of hydroquinone alone (P < 0.01). After 18 - 48 hour culture, the necrotic rate
      in amifostine + hydroquinone group was lower than that in the group of
      hydroquinone alone (P < 0.05). CONCLUSION: Amifostine can protect cell from
      hydroguinone-induced bone marrow damage through inhibition on cell apoptosis, and
      decrease in cell necrosis.

PMID- 15256146
TI  - [Case-only study on the relationship between genetic polymorphisms in toxicant
      metabolizing enzymes and risk of occupational chronic benzene poisoning].
AB  - OBJECTIVE: To explore the effects of interaction between environmental exposure
      factors and genetic polymorphism in toxicant metabolizing enzymes on risk of
      occupational chronic benzene poisoning. METHODS: One hundred and fifty-two cases
      of chronic benzene poisoning were analyzed for the risk by case-only study.
      RESULTS: The frequency of non-null GSTT1 gene in benzene poisoning workers with
      moderate benzene exposure level was higher than that in cases with lower benzene
      exposure (68.63% vs 38.00%, OR(adj) = 4.32, 95% CI 1.75 - 10.66, P = 0.002). The
      frequency of NQO1 C.609T/T gene in alcohol drinking group was higher than that in
      non-drinking group (61.11% vs 20.00%, OR(adj) = 8.03, 95% CI 2.28 - 28.25, P =
      0.001), moreover, it was higher in workers with smoking and drinking than that in
      the rest group, and in drinking x exposure level workers than that in non
      drinking x exposure level workers (85.71% vs 22.76%, OR(adj) = 18.62, 95% CI 2.01
      - 172.72, P = 0.01 and 61.11% vs 20.00%, OR(adj) = 3.18, 95% CI 1.55 - 6.52, P =
      0.002 respectively). The frequency of non-null GSTM1 gene was also higher in
      drinking x exposure level workers than that in non-drinking x exposure level
      workers (66.67% vs 47.06%, OR(adj) = 1.99, 95% CI 1.05 - 3.76, P = 0.036).
      CONCLUSION: There is interaction between the polymorphism of GSTT1 gene and
      moderate benzene exposure level; non-null GSTM1 gene and drinking x exposure
      level increase the risk of occupational chronic benzene poisoning; polymorphism
      of NQO1 gene C.609 also interacts with drinking, while polymorphism of NQO1 gene
      and drinking x smoking may further increase the risk of occupational chronic
      benzene poisoning.

PMID- 15256147
TI  - [DNA damages of liver cells and expressions of DNA damage repair genes in rats
      exposed to vinyl chloride monomer].
AB  - OBJECTIVE: To study DNA damages of liver cells in rats exposed to vinyl chloride
      monomer (VCM), and the expressions of DNA damage repair enzymes including O(6)
      methyl guanine-DNA methyl transferase (MGMT), X-ray repair cross-complementing
      group 1 (XRCC1) and X-ray repair cross-complementing group 3 (XRCC3); and to
      explore the repair mechanism of DNA damage induced by VCM. METHODS: Rats were
      exposed to VCM by intraperitoneal injection. DNA damages were detected by single
      cell gel electrophoresis (comet assay). The expressions of DNA damage repair
      enzymes were measured by immunohistochemical methods. RESULTS: The percentages of
      comet cells in low, moderate, and high dose groups (11.75%, 12.38%, and 17.63%,
      respectively) were greater than that of control (5.67%). The latter two groups
      were significantly different from that of control (P < 0.05, P < 0.01). The
      expressions of MGMT and XRCC1 decreased, and XRCC3 increased with the dose of VCM
      increased. DNA damage was correlated with the expression of XRCC3 (r = 0.438, P =
      0.067). CONCLUSION: VCM can cause DNA damage of liver cells with dose-response
      relationship. DNA damage repair enzymes take part in the repairing of DNA damage
      induced by VCM.

PMID- 15256149
TI  - [Autopsy on two cases of acute hydrogen phosphide poisoning].

PMID- 15256148
TI  - [Relationship of genetic polymorphism of microsomal epoxide hydrolase with
      susceptibility of chronic benzene poisoning].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphisms of
      microsomal epoxide hydrolase (mEH) and susceptibility of chronic benzene
      poisoning (BP). METHOD: A case-control study was conducted. 152 BP patients and
      152 workers occupationally exposed to benzene without poisoning manifestations
      were investigated. Polymerase chain reaction-restrained fragment length
      polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide
      polymorphisms (SNPs) on c.113 and c.139 of mEH gene. RESULTS: The risk of BP for
      individuals carrying mEHc.113 C/C genotype was 0.60 (OR = 0.60, 95% CI: 0.37 -
      0.97, P = 0.04) of those carrying T/T and T/C genotypes. In non-smoking
      population, the risk of BP for subjects carrying mEHc.113 C/C genotype was 0.56
      (OR = 0.56, 95% CI: 0.33 - 0.96, P = 0.03) of those carrying T/T and T/C
      genotypes, and in non-drinking population, the individuals carrying mEHc.113 C/C
      genotype was 0.51 (OR = 0.51, 95% CI: 0.30 - 0.86, P = 0.01) of those carrying
      T/T and T/C genotypes. CONCLUSION: The subjects carrying mEHc.113 C/C genotype
      and together with non-smoking or non-drinking habit may have lower risk of
      chronic benaene poisoning.

PMID- 15256150
TI  - [Evaluation of recent thymic output function in benzene-exposed workers].
AB  - OBJECTIVE: To analyze the content of signal joint T-cell receptor excision DNA
      circles signal joint T-cell receptor excision DNA circles (sjTRECs) within
      peripheral blood mononuclear cells (PBMCs), thereby to infer the level of naive T
      cells and the recent thymic output function in benzene-exposed workers. METHODS:
      Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells
      from 11 normal individuals and 62 benzene-exposed workers were performed by real
      time polymerase chain reaction (PCR) and TaqMan technique. RESULTS: The median
      value of sjTRECs copies/1,000 PBMCs was 7.81 in normal individuals whereas it was
      2.56 copies/1 000 PBMCs in age-unadjusted benzene-exposed workers (P < 0.01). And
      its levels were obviously different between two different age groups: that in 30
      year-old group (1.76 copies/1,000 PBMCs, n = 23) was less than <or= 30-years-old
      group (3.19 copies/1,000 PBMCs, n = 39, P < 0.05). CONCLUSIONS: Benzene exposure
      may influence the recent thymic output function, and the sjTRECs levels may
      relate with the age of benzene-exposed workers.

PMID- 15256151
TI  - [Stimulatory response to the oxidation of benzidine and other xenobiotics
      mediated by lipoxygenase in the presence of phenothiazines].
AB  - OBJECTIVE: To test the possibility that certain efficient substrates for
      lipoxygenase (LOX) produce shuttle oxidants that stimulate the generation of
      reactive oxygen species from other chemicals. METHODS: Metabolic interactions
      were conducted in vitro between chlorpromazine (BZ) or other phenothiazines and
      benzidine or other xenobiotics mediated by soybean lipoxygenase (SLO) or purified
      human term placental lipoxygenase (HTPLO) in the presence of hydrogen peroxide,
      and the rates of xenobiotics oxidation were measured by spectroscopic analysis.
      RESULTS: Chlorpromazine cation radical (CPZ(*+)) generated by lipoxygenase
      triggered a rapid oxidation of benzidine to benzidine diimine cation. Under the
      experimental conditions used, the metabolic interaction resulted in a 42-fold
      greater stimulation than BZ alone in the rate of BZ oxidation. The magnitude of
      stimulation of benzidine oxidation exhibited a dependence on the pH of the
      reaction medium, amount of the enzyme, and concentration of chlorpromazine, BZ,
      and hydrogen peroxide. A number of other phenothiazines were also found to
      stimulate BZ oxidation, albeit to a lesser degree. Chlorpromazine cation radical
      stimulated the oxidation of all six other xenobiotics tested. The highest
      stimulation (94-fold) was noted in the oxidation of tetramethyl phenylenediamine
      to Wursters blue radical, while the lowest stimulatory response (2-fold) was
      observed in guaiacol. Preliminary data showed that purified HTPLO also displayed
      a similar stimulatory response to benzidine oxidation in the presence of
      chlorpromazine. CONCLUSION: Both soybean lipoxygenase and purified human term
      placental lipoxygenase can mediate stimulatory response to the oxidation of
      benzidine and other xenobiotics in the presence of phenothiazines.

PMID- 15256152
TI  - [Effects of lithium on primary cultured cerebrocortical neurons of rat].
AB  - OBJECTIVE: To explore the neuroprotection and the impact on brain development of
      lithium, the effects of lithium salt on the growth and survival of primary
      cultured cerebrocortical neurons were studied. METHODS: The technique of primary
      cultured cerebrocortical neurons of newborn rats with serum-free medium was
      established, and the growth and survival of neurons treated with different doses
      of lithium chloride (0.625, 1.250, 2.500, 5.000, 10.000 mmol/L) were observed.
      The length of neuronal synapse, cell viability by MTT reduction assay were also
      measured. RESULTS: The neurons were brighter, germinated rapidly, the neuronal
      synapse lengthened markedly, and the neurons viability was also better after
      treated with lithium chloride. Among the five doses, 5.000 mmol/L had the best
      effect [(53.80 +/- 5.84) micro m, P < 0.01]. CONCLUSION: Lithium chloride can
      promote the growth and survival of neurons.

PMID- 15256153
TI  - [Effect of low benzene exposure on workers' peripheral blood parameters of
      different similar exposure groups].
AB  - OBJECTIVE: To study the relationship between low benzene exposure doses with
      workers' peripheral blood parameters of different similar exposure groups (SEG).
      METHODS: The workers were from a shoe factory and divided into different SEG,
      according to the observation method and sampling method. Exposure levels, blood
      samples and job histories were collected. The relationship between benzene level
      and blood routine were analyzed using multiple regression method. RESULTS: Five
      SEGs were defined. No significant differences were found among different SEG in
      length of service, smoking, drinking, blood routine and symptoms except for ages.
      Significant negative correlation (r = -0.36, P < 0.05) between benzene exposure
      levels and white blood cell counts were found by multiple regression analysis.
      Similar negative correlation was also found between length of benzene exposure
      and red blood cell counts (r = -0.29, P < 0.05). No significantly statistical
      relationships were found between benzene exposure and red blood cell counts or
      platelet count. CONCLUSION: SEGs method is sensitive for determining the
      relationship between benzene exposure levels and white blood cell counts. Further
      study is needed by increasing the number of workers to study the relationship
      between low benzene exposure and peripheral blood parameters.

PMID- 15256154
TI  - [Study on the genetic damage in mice induced by the volatile organic compounds of
      decoration materials].
AB  - OBJECTIVE: To study genetic damage of mice caused by the volatile organic
      compounds (VOC) of decoration materials. METHODS: Fifty-five hotel guest rooms
      newly decorated within 6 months and 18 hotel guest rooms not decorated within 3
      years were selected to determine the concentrations of 6 main VOC (benzene,
      methylbenzene, dimethylbenzene, ethyl acetate, butyl acetate, formaldehyde) in
      the air. Mice were exposed to VOC with the concentrations of 5, 10, 20, 40 times
      respectively as high as those present in the newly decorated rooms in an exposure
      cabinet for 15 days. DNA damage of peripheral lymphocytes of the mice was
      determined by single cell gel electrophoresis (SCGE) and bone marrow micronucleus
      test. RESULTS: The concentrations of benzene, methylbenzene, dimethylbenzene,
      ethyl acetate, butyl acetate and formaldehyde in the rooms newly decorated within
      6 months (6.50, 3.00, 6.70, 41.33, 1.70 and 0.14 mg/m(3) respectively) were
      significantly higher than those in rooms not decorated within 3 years (0.08,
      0.94, 1.38, 0.25, 0.25, 0.01 mg/m(3), P < 0.01). DNA damage rates of peripheral
      lymphocytes in the concentrations of 10, 20, 40 times of exposure groups were
      significantly higher than those in the control groups (P < 0.05 or P < 0.01), and
      the frequencies of micronucleus in the mice exposed to 40 times of concentration
      was significantly higher than that in control group. CONCLUSION: High
      concentrations of the volatile organic chemical compounds may cause genetic
      damage in mice. SCGE test is more sensitive than micronucleus test.

PMID- 15256155
TI  - [Effect of phosgene on apoptosis of alveolar type II cells and vascular
      endothelial growth factor in exposed mice].
AB  - OBJECTIVE: To study the apoptosis of alveolar type II cells, alterations of
      vascular endothelial growth factor (VEGF), VEGF receptor (Flt1) in serum and lung
      and expression of VEGF mRNA in lung in pulmonary edema mice induced by phosgene.
      METHODS: Twenty-six BALB/C mice were randomly divided into 2 groups: control
      group, exposed group (13 mice in each group). Mice of exposed group were
      intoxicated by inhalation of phosgene 11.9 mg/L for 5 minutes. Mice of control
      group were treated as the same way by inhalation of air. Isolation of mice
      alveolus type II cells 4 h after intoxication was carried out to observe their
      apoptosis under electron microscope. Contents of VEGF and Flt1 in lung and serum
      by ELISA, and expression of VEGF mRNA were determined. RESULTS: Alveolar type II
      cells were identified by tannic acid staining and electron microscopy. After
      exposed to 11.9 mg/L of phosgene for 5 minutes, the apoptotic body in alveolus
      type II cells was found in exposed group. The contents of VEGF in serum and lung
      and Flt1 in lung of exposed mice [(134.07 +/- 120.26), (477.76 +/- 98.06),
      (1,2818.48 +/- 2,304.15) pg/ml] were significantly lower than those of control
      group [(445.57 +/- 173.30), (1,026.87 +/- 474.56), (21,976.51 +/- 7,421.01)
      pg/ml, P < 0.05] but the content of Flt1 in serum [(2,369.56 +/- 381.70) pg/ml]
      was higher than that in control group [(1,898.00 +/- 453.69) pg/ml, P < 0.05].
      The expression of VEGF mRNA in pulmonary edema mice was decreased. CONCLUSION:
      Phosgene can induce apoptosis of alveolar type II cells, and decrease in the
      content of VEGF and Flt1, and expression of VEGF mRNA in lung.

PMID- 15256156
TI  - [Effect of acute phosgene inhalation on antioxidant enzymes, nitric oxide and
      nitric-oxide synthase in rats].
AB  - OBJECTIVE: To study the effect of acute phosgene inhalation on the antioxidant
      enzymes, nitric oxide (NO) and nitric oxide synthase (NOS) in rats. METHODS:
      Phosgene was produced by decomposing bis (trichdomethyl) carbonate in the
      presence of N,N-dimethyl formamide. SD rats were randomly divided into two
      groups: control and phosgene exposure groups. In a special experimental device
      with equipment modulating the gas flow, phosgene exposed rats inhaled phosgene
      quantitatively for five minutes. Two hours later, all the rats were sacrificed
      and the ratio of wet weight to dried weight of lung (WW/DW) was calculated.
      Peripheral blood, serum and liver were collected to examine the activities of
      antioxidant enzymes including glutathione S-transferase (GST), superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), NOS, and NO
      level. The total content of proteins were also determined. RESULTS: The WW/DW
      ratio of lung in phosgene exposure group was much higher than that in control
      group (P < 0.01). The activities of GST in serum and liver of phosgene exposure
      group increased significantly (P < 0.05). The activities of SOD, CAT, GSHPx and
      NOS in serum or blood and liver of phosgene exposure group were also increased
      significantly (P < 0.05). But the content of NO was significantly decreased (P <
      0.01). CONCLUSION: Acute phosgene inhalation may cause a dramatically changes of
      several antioxidant enzyme activities, and acute injury of liver to some extent
      in rats. The latter is related to reactive oxygen species. But the elevation of
      antioxidant enzyme activities suggests that antioxidative treatment for acute
      phosgene poisoning should not be considered first.

PMID- 15256157
TI  - [Effect of taurine on NOS activity in hippocampus of rat exposed lead].
AB  - OBJECTIVE: To study the effect of taurine on lead-induced damage to the ability
      of learning and memory. METHODS: Using NADPH-d histochemistry method to study the
      change of rat NOS positive neurons in hippocampus. Rats in experimental groups
      were fed with different doses of lead in drinking water (0.011, 0.110 g/L), and
      different doses of taurine (5, 10 g/kg). RESULTS: Taurine (10 g/kg) could
      increase the number of NOS positive neurons in CA1 and dentate gyrus subregion in
      hippocampus of rats exposed to lead. The number of NADPH-d positive neurons in
      CA1 and dentate gyrus subregion for low lead (0.011 g/L) and high taurine (10
      g/kg) group (51.80 +/- 4.68, 47.40 +/- 4.20, respectively) were higher than those
      in the low lead (0.011 g/L) group (41.20 +/- 5.32, 39.87 +/- 3.81, respectively,
      P < 0.05). CONCLUSION: Taurine may antagonize lead-induced damage to the ability
      of learning and memory.

PMID- 15256158
TI  - [A clinical analysis of 50 cases of medicament-like dermatitis due to
      trichloroethylene].
AB  - OBJECTIVE: To investigate the clinical manifestations, complications and
      treatment of medicament-like dermatitis due to trichloroethylene (TCE), so as to
      provide basis for studying its etiology and mechanism. METHODS: Fifty patients
      with dermatitis due to TCE from 1997 to 2000 were analysed retrospectively.
      RESULTS: The occurrence of the dermatitis was not parallel to TCE exposure
      levels, without significant dose-effect relationship. This disease could be
      caused by both inhalation and skin exposure. The latency period of TCE dermatitis
      ranged from 5 to 66 days, and the average was 31.5 d (Medium). The major clinical
      manifestations included skin lesions, fever, superficial lymph node swelling and
      liver dysfunction. Infection was the major complication. Glucocorticoid was
      effective for treatment of this disease. CONCLUSION: The clinical manifestations
      due to TCE exposure were similar to dermatitis medicamentosa. The major clinical
      types of TCE dermatitis included exfoliative dermatitis and erythema multiforme.
      The dermatitis is considered to be mediated by delayed-type (IV)
      hypersensitivity. The key factors to treat this disease successfully included the
      use of glucocorticoid in time with sufficient dose and full course, professional
      skin care, active treatment to protect the liver and to avoid infection.

PMID- 15256159
TI  - [Studies on the injury effects of hippocampus induced by high power microwave
      radiation in rat].
AB  - OBJECTIVE: To study the changes of morphology and function in rat hippocampus
      induced by high power microwave (HPM) radiation. METHODS: Fifty male Wistar rats
      were radiated by HPM. Then their learning and memory abilities were tested with Y
      maze and were sacrificed 6 h, 1 d, 3 d and 7 d after radiation. The hippocampus
      was taken out to study the basic pathologic changes, apoptosis and the
      expressions of neuron-specific enolase (NSE) and glial fibrillary acidic protein
      (GFAP) by means of HE staining, Nissel body staining, in situ terminal end
      labeling and immunohistochemistry. RESULTS: The learning and memory abilities of
      rats reduced significantly after HPM radiation. HPM also resulted in rarefaction,
      edema and hemangiectasia of hippocampus, nervous cells degeneration and necrosis,
      decrease or disappearance of Nissel bodies. The injuries were more serious in
      field CA4 and dentate gyrus, which showed dose-effect relationship, and were
      progressively aggravated within 7 days. The apoptosis cells were significantly
      increased. NSE was increased in neurons. The NSE positive areas were also seen in
      the interstitial matrix and blood vessels. GFAP was increased in astrocytes,
      which became shorter and thicker. CONCLUSION: HPM can damage the abilities of
      learning and memory and results in morphologic changes in hippocampus. The major
      pathologic changes are degeneration, apoptosis and necrosis of neurons and edema
      in interstitium. NSE and GFAP play an important role in the pathologic process.

PMID- 15256160
TI  - [Gastrointestinal hemorrhage induced by heat stroke].

PMID- 15256162
TI  - [Effect of different concentrations of lead acetate on primary-cultured cerebro
      cortical neurons].

PMID- 15256161
TI  - [Experimental study on carbon disulphide-induced vascular endothelial damage and
      the intervention of vitamin C].

PMID- 15256163
TI  - [Effect of sodium arsenite on the proliferation and cell cycle of keratogenetic
      cells].

PMID- 15256164
TI  - [Screening of risk factors of time to pregnancy for women workers exposed to
      carbon disulphide].

PMID- 15256165
TI  - [Analysis of heart rate variability in coal miners with pneumoconiosis].

PMID- 15256166
TI  - [Repair gene for DNA damage relating to benzene poisoning].

PMID- 15256167
TI  - [Preliminary study on monitoring the time weighted average permissible
      concentration of dust in the air by quartz crystal microbalances].

PMID- 15256168
TI  - [Some experiences in the treatment for trichloroethylene-induced medicamentosa
      like dermatitis].

PMID- 15256169
TI  - [Blood perfusion treatment for severe acute organophosphorus poisoning].

PMID- 15256170
TI  - [Three cases of acute p-nitrochlorobenzene poisoning].

PMID- 15256171
TI  - [Two cases of lead poisoning-induced encephalopathy in children].

PMID- 15256172
TI  - [One case of acute dimethyl formamide poisoning-induced subacute liver necrosis].

PMID- 15256173
TI  - [Application of standards for hearing monitoring and protection to occupational
      noise exposed people].

PMID- 15256174
TI  - [Investigation on mercury poisoning event in a glass instrument and meter plant].

PMID- 15256175
TI  - [Using a designed questionary to evaluate occupational hazard in new project].

PMID- 15256176
TI  - [Analysis on the agreement of two diagnostic standards for pneumoconiosis].

PMID- 15256177
TI  - New guidelines on the treatment of epilepsy with the new antiepileptic drugs,
      from the Epilepsy Foundation.

PMID- 15256178
TI  - Antiepileptic drugs and memory.
AB  - Impaired memory is among the most common complaints of patients with epilepsy.
      Multiple factors contribute to memory impairment in patients with epilepsy. Thus,
      delineation of the effects of antiepileptic drugs (AEDs) on memory in clinical
      populations faces methodological difficulties. Further, subjective perception of
      memory problems by patients is influenced by mood. However, there is evidence
      from animal and healthy volunteer studies supporting an independent potential for
      AEDs to impair memory. Differential AED effects on memory have been observed, and
      AED effects may interact with focal brain lesions. Memory impairment from AEDs is
      a greater concern at the age extremes, although the effects of AEDs, especially
      the newer agents, have not been thoroughly studied in these populations. Well
      controlled studies are needed to understand the underlying mechanisms and to
      further delineate the magnitude and relative effects of AEDs on memory.

PMID- 15256179
TI  - Emergence of spontaneous seizures during the year following lithium/pilocarpine
      induced epilepsy and neuronal loss within the right temporal cortices.
AB  - Thirty days after the induction of seizures in 16 rats with lithium (3 mEq/kg)
      and pilocarpine (30 mg/kg), the numbers of episodes of motor seizures (rapid
      forelimb clonus) during daily 10-minute observational periods were recorded for
      11 months. The proportions of neuronal loss were ranked using two methods by
      light microscopy for all structures between the posterior and anterior
      commissures. Amounts of damage within the dentate gyrus, hilus (CA4), and CA3
      field were most strongly correlated with numbers of seizures per month about 6
      months before the brains were removed. The strongest correlations occurred
      between the amounts of damage within the right temporal cortices, even after the
      variance associated with damage within the dentate gyrus had been removed, and
      the numbers of seizures during the last 2 months. These results may explain the
      greater proportion of spontaneous seizures that begin with left side forelimb
      clonus and suggest a particular sensitivity of the right side of the brain to
      either their initiation or their consequences.

PMID- 15256180
TI  - Effect of food deprivation during early development on cognition and neurogenesis
      in the rat.
AB  - Food deprivation has been recognized as having pronounced beneficial effects in
      adult animals, increasing longevity, reducing seizure susceptibility, and
      enhancing resistance to neurotoxins. It is not known whether food deprivation in
      developing animals is neuroprotective or harmful. To evaluate the effects of food
      deprivation on brain development, we evaluated visual-spatial learning and memory
      and neurogenesis in the dentate gyrus of the hippocampus in food-deprived (FD)
      and well-fed (WF) rats. To induce food deprivation, pups were removed from their
      dams for 12 hours per day from Postnatal Day (P) 2 to P19. FD and WF rat pups
      were then subjected to status epilepticus (SE) induced by lithium-pilocarpine at
      P20. After SE, neurogenesis was measured, while in another group of P38 rats,
      learning and memory were evaluated using the Morris water maze. Food deprivation
      was found to reduce neurogenesis when assessed after the period of food
      deprivation. Although SE reduced neurogenesis in the WF animals, it had little
      effect additional to food deprivation on neurogenesis in the FD rats. Compared
      with the WF group, FD rats had a mild impairment in memory in the water maze
      testing after SE. Our study demonstrates that food deprivation during the
      neonatal period in rats is associated with a decrease in neurogenesis and mild
      impairment of visual-spatial memory. Although SE decreased neurogenesis in the WF
      group, in FD animals, SE did not reduce neurogenesis more than what was seen with
      food deprivation alone. Our results suggest that although food deprivation during
      early development reduces dentate gyrus neurogenesis, the reduced neurogenesis is
      not a major factor in cognitive impairment after SE in FD rats.

PMID- 15256181
TI  - Neuroethological study of status epilepticus induced by systemic pilocarpine in
      Wistar audiogenic rats (WAR strain).
AB  - The administration of pilocarpine (PILO) is widely recognized as resulting in an
      experimental model of temporal lobe epilepsy; it is characterized by induction of
      status epilepticus (SE) and spontaneous recurrent seizures after a latent period.
      We provide in this work a neuroethological description of the SE induced by PILO.
      Behavioral evaluations were made in Wistar Audiogenic Rats (WARs) and Wistar
      resistant (R) animals. The experimental group (R) and WARs were pretreated with
      methyl scopolamine (1mg/kg ip) and injected with PILO (R animals, 340-380 mg/kg
      ip; WARs, 240-280 mg/kg ip). Among R animals, 36% developed SE, and among WARs,
      53%. The control group (R animals and WARs) was injected only with methyl
      scopolamine plus saline. The ETHOMATIC method was used for evaluation of
      seizures. Sequences included in the analysis were chosen using (1) fixed
      observation windows and (2) behavioral triggers. The R group showed that the
      threshold for seizure is variable, so seizure onset and behavioral evolution were
      better described using behavioral triggers than fixed observation windows. The
      observation windows selected in similar duration intervals do not characterize
      the seizures. Sequential analysis in the WAR group showed high mortality after SE
      and greater susceptibility to PILO, compared with R animals. We conclude that
      with neuroethological tools it is possible to better map the sequence and
      evolution of SE induced by PILO compared to only using behavioral and arbitrary
      seizure severity scales. This sequence is faster and stronger in severity when
      WARs are compared with R animals. Although the WARs underwent an evolution of SE
      in some way equivalent to that of R animals, some rats presented tonic-clonic
      convulsions after PILO injection, very similar to acute audiogenic seizures, a
      brainstem-dependent model. The current data also point to the PILO-plus-WAR
      combination as a suitable protocol to study the genetic-epilepsy connection in
      experimental temporal lobe epilepsy.

PMID- 15256182
TI  - Lamotrigine does not impair motor performance and spontaneous behavior in
      developing rats.
AB  - No data exist on possible effects of lamotrigine on development. Therefore we
      performed an ontogenetic study with repeated administration of lamotrigine (10
      and/or 20 mg/kg ip for 6 consecutive days) starting in rats 12 and 25 days old
      (Postnatal Days (PD) 12 and 25). Body weights of these animals were checked,
      their motor skills were repeatedly tested, and their behavior in an open field
      was studied at three intervals after the end of treatment. Body weight of PD12
      animals increased more slowly than that of control siblings; this difference
      disappeared till adulthood. There were only transient changes on the bar holding
      test in the PD12 group and on the rotorod test in the PD25 group. The open-field
      test demonstrated greater exploratory activity (rearing) in the PD25 group only
      at the age of 48 days but not 1 month later. Lamotrigine administered repeatedly
      at early developmental stages did not change motor abilities and behavior in an
      open field.

PMID- 15256183
TI  - Measuring stigma in children with epilepsy and their parents: instrument
      development and testing.
AB  - PURPOSE: The goal of this work is to describe psychometric properties of two
      scales measuring perceived stigma in children with epilepsy and their parents.
      METHODS: Data were collected for the parent scale in two samples: parents of 173
      children with epilepsy and of 224 children with new-onset seizures. The child
      scale was tested in the chronic sample. Content validity, internal consistency
      reliability, and construct validity were tested. RESULTS: Both scales had strong
      internal consistency reliability and construct validity. Higher scores were
      associated with greater seizure severity scores. In the parent scale, lower
      scores were associated with more positive mood, less worry, and more family
      leisure activities. In the child scale, higher scores were correlated with more
      negative attitude, greater worry, poorer self-concept, and more depression
      symptoms. CONCLUSIONS: Both scales were found to have strong psychometric
      properties. They are short, and items are easy to understand. These scales have
      potential for use in research and in the clinical setting to measure stigma.

PMID- 15256184
TI  - Patient-specific seizure onset detection.
AB  - This article presents an automated, patient-specific method for the detection of
      epileptic seizure onset from noninvasive electroencephalography. We adopt a
      patient-specific approach to exploit the consistency of an individual patient's
      seizure and nonseizure electroencephalograms. Our method uses a wavelet
      decomposition to construct a feature vector that captures the morphology and
      spatial distribution of an electroencephalographic epoch, and then determines
      whether that vector is representative of a patient's seizure or nonseizure
      electroencephalogram using the support vector machine classification algorithm.
      Our completely automated method was tested on noninvasive electroencephalograms
      from 36 pediatric subjects suffering from a variety of seizure types. It detected
      131 of 139 seizure events within 8.0+/-3.2 seconds of electrographic onset, and
      declared 15 false detections in 60 hours of clinical electroencephalography. Our
      patient-specific method can be used to initiate delay-sensitive clinical
      procedures following seizure onset, for example, the injection of a functional
      imaging radiotracer.

PMID- 15256185
TI  - The impact of early versus late anticonvulsant reduction after ketogenic diet
      initiation.
AB  - The ideal timing of anticonvulsant reduction for a child started on the ketogenic
      diet is unclear. The records of 81 children started on the ketogenic diet
      consecutively over a 2-year period were reviewed for a 6-month period after diet
      initiation. During their first 6 months on the ketogenic diet, medications were
      tapered in 53 of 81 (65%) patients, with 30 of 53 (57%) considered "early"
      (tapered during diet initiation or within the first month afterward). No
      differences were seen between the early and late groups with respect to
      percentage with > 90% seizure reduction at 3 months (47% vs 48%), diet duration
      (1.1 vs 0.9 years), percentage remaining on the ketogenic diet to date (73% vs
      65%), or improved alertness (63% vs 57%). Nine of fifty-three (17%) had transient
      seizure increases during medication tapering, with no correlation to the timing
      in which this occurred; however, five were taking benzodiazepines or
      barbiturates. All had > 50% seizure reduction at 3 months despite the transient
      worsening. Early reduction of anticonvulsants in children initiated on the
      ketogenic diet appears to be safe and well tolerated. However, it offers no
      specific advantage compared with a later taper.

PMID- 15256186
TI  - Auditory event-related potentials (P300) in the identification of psychogenic
      nonepileptic seizures.
AB  - The feasibility and conceivable value of postictal event-related potential (ERP)
      recordings were studied in patients with nonepileptic seizures (NES) admitted for
      long-term video/EEG monitoring. Ten patients with NES underwent preictal (on
      hospital admission) and postictal (< or =6 hours after seizure) ERP recordings of
      an auditory oddball paradigm. Additionally, 10 temporal lobe epilepsy (TLE)
      patients with partial seizures and secondary generalization underwent preictal,
      postictal (< 6 hours after seizures), and interictal (7-48 hours after seizure)
      ERP recordings. We recently reported that ERPs recorded in TLE patients with
      partial epilepsy undergo a temporary change postictally, while returning to their
      preictal state during interictal recordings. In the current study intraclass
      correlations, transformed into z scores, are used to determine test-retest
      validity of repeated ERP recordings. An independent sample t test with z scores
      for the comparison of preictal and postictal recordings showed that ERP
      activation differed between NES and TLE patients (P=0.009). More specifically,
      ERP recordings in the preictal and postictal states were similar in NES patients,
      but dissimilar in TLE patients. On the other hand, this dissimilarity in ERPs
      disappeared when comparing z scores for the preictal and postictal recordings in
      NES patients with z scores for the preictal and interictal recordings in TLE
      patients. This further supports the notion that identical waveforms during
      preictal and postictal recordings in NES patients reflect nonepileptic seizure
      activity. The current findings suggest that postictal ERP recordings are useful
      in the diagnosis of NES and differentiate TLE from NES.

PMID- 15256187
TI  - Lamotrigine for patients with juvenile myoclonic epilepsy following prior
      treatment with valproate: results of an open-label study.
AB  - This open-label study was designed to evaluate lamotrigine monotherapy as a
      possible alternative in patients with juvenile myoclonic epilepsy who previously
      failed treatment with valproate. Patients (n=63) were transitioned from valproate
      to lamotrigine during an 8-week escalation phase followed by 24 weeks of
      lamotrigine monotherapy. On Week 24 of the treatment phase, investigators judged
      that 50 and 67% of patients completing the study had shown mild, moderate, or
      marked improvement in adverse events and global clinical status, respectively,
      and 76% of patients rated lamotrigine as somewhat better (13%) or much better
      (63%) than valproate. The majority of patients completing the study experienced
      no deterioration of seizure control when switching from valproate to lamotrigine.
      These results support additional research on lamotrigine in juvenile myoclonic
      epilepsy.

PMID- 15256188
TI  - Effects of epilepsy on autonomic nervous system and respiratory function tests.
AB  - We have investigated autonomic nervous system function during the interictal
      period in epileptic patients and the possible effects of autonomic dysfunction on
      respiratory functions. A total of 32 epileptic patients (23 generalized, 9
      partial epilepsy) and 32 healthy volunteers were involved. Sympathetic skin
      response (SSR), for evaluating the sympathetic nervous system, and RR interval
      variation (RRIV) were measured at the beginning and third month of antiepileptic
      treatment, and respiratory function tests (RFTs) were performed. In patients with
      partial epilepsy, SSR latency in the upper extremity (1.3+/-0.2 s) was longer
      than that of controls (1.2+/-0.3 s) at baseline (P=0.05), and was significantly
      reduced (1.1+/-0.3 s) after treatment (P<0.05). RRIV values of patients with
      generalized epilepsy were statistically significantly lower than those of
      controls (P<0.01). However, deep breathing RRIV values (32.6+/-15.3%) of patients
      were lower than those (43.0+/-18.2%) of controls (P<0.05). Sympathetic
      dysfunction was determined in patients with partial epilepsy and parasympathetic
      dysfunction in patients with generalized epilepsy. No abnormality was observed on
      RFTs for both patients with partial epilepsy and patients with generalized
      epilepsy.

PMID- 15256190
TI  - Severity of depressive symptoms, hippocampal sclerosis, auditory memory, and side
      of seizure focus in temporal lobe epilepsy.
AB  - The relationship between severity of depressive symptoms and performance on three
      Wechsler Memory Scale-III auditory memory and learning subtests was examined in
      84 inpatients diagnosed with medically intractable seizures of left (n=46, LTLE)
      or right (n=38, RTLE) temporal lobe origin. Depressive symptom severity was
      associated with auditory recall test performance in individuals with LTLE, but
      not RTLE. Multiple regression analyses indicated that severity of depressive
      symptoms, hippocampal sclerosis, and naming ability were significant predictors
      of auditory memory test performance in LTLE; however, hippocampal sclerosis was
      the only significant predictor of auditory memory in RTLE. Results demonstrate
      the importance of hippocampal sclerosis, greater self-report of depressive
      symptoms, and poor naming ability as independent predictors of poor auditory
      memory and learning abilities. Results suggest that a complex relationship exists
      among multiple risk factors that combine to influence performance on auditory
      memory tests as a function of side of seizure focus.

PMID- 15256189
TI  - Serum prolactin levels for differentiation of nonepileptic versus true seizures:
      limited utility.
AB  - Frequently occurring nonepileptic psychogenic seizures (PNES) are a cause of
      substantial morbidity. Differentiation of these from true seizures may sometimes
      be very difficult. Serum prolactin level estimation following the event has been
      described as a useful test for this purpose. We conducted this study to assess
      the role of this test in diagnosis of PNES. Serum prolactin was estimated from
      venous blood samples of 19 patients (13 females, 6 males) with PNES and 17
      patients (5 females, 12 males) with true complex partial seizures with or without
      secondary generalization. The age range was 12-39 years in the PNES group and 9
      42 years in the true seizure group. Five patients (all females) in the PNES group
      (26.3%) had raised prolactin levels, all of them having greater than twice normal
      levels. In the true seizure group, 10 of 17 (58.8%) patients had raised levels;
      only 3 (17.6%) of these had greater than twice normal levels. The difference in
      percentage of patients with abnormal prolactin levels between these groups was
      not found to be significant. We demonstrate that serum prolactin level estimation
      is not a useful method for differentiation of psychogenic nonepileptic from true
      epileptic seizures.

PMID- 15256191
TI  - Efficacy and tolerability of conversion to monotherapy with lamotrigine compared
      with valproate and carbamazepine in patients with epilepsy.
AB  - OBJECTIVE: This randomized, open-label study was designed to compare the efficacy
      and tolerability of lamotrigine monotherapy with those of valproate and
      carbamazepine monotherapy in patients with epilepsy whose seizures were
      uncontrolled on their prestudy antiepileptic drug monotherapy. METHODS: Patients
      meeting eligibility criteria were randomized 2:1 to lamotrigine:carbamazepine or
      lamotrigine:valproate. The treatment phase was divided into a 4-week dose
      escalation phase (Weeks 1-4), during which lamotrigine, carbamazepine, or
      valproate was added to patient's prestudy monotherapy; an 8-week add-on phase
      (Weeks 5-12), during which patients were stabilized on both the study medication
      and their prestudy antiepileptic therapy; an 8-week withdrawal phase (Weeks 13
      20), during which prestudy antiepileptic therapy could be withdrawn if clinically
      appropriate; and an 8-week monotherapy phase (Weeks 21-28), during which patients
      could be treated with study medication as monotherapy. RESULTS: The numbers of
      patients randomized to the carbamazepine and valproate arms of the study were 144
      (98 lamotrigine, 46 carbamazepine) and 158 (105 lamotrigine, 53 valproate),
      respectively. Successful monotherapy sustained for at least 7 weeks was achieved
      in comparable percentages of patients in the lamotrigine group (56%) and the
      carbamazepine group (54%) and in more patients in the lamotrigine group (49%)
      than the valproate group (40%). Among monotherapy completers, the percentage of
      patients with zero seizures during the monotherapy phase was comparable for
      lamotrigine (41%) and carbamazepine (30%) and significantly higher (P<0.05) with
      lamotrigine (32%) than with valproate (11%). No differences between treatments
      were observed with respect to time to treatment failure or time to first seizure.
      Lamotrigine was also better tolerated than carbamazepine or valproate.
      CONCLUSION: Lamotrigine monotherapy was as effective as and better tolerated than
      carbamazepine or valproate monotherapy in patients whose seizures were
      uncontrolled on their prestudy antiepileptic drug monotherapy.

PMID- 15256192
TI  - Psychogenic status epilepticus in children.
AB  - Epilepsy features, psychiatric profile, psychosocial factors, and outcome are
      described for six children (three males) aged 5-15 years (mean 12.1) with
      psychogenic status epilepticus (PSE), i.e., prolonged or repetitive psychogenic
      seizures (PSs), >30 minutes, simulating status epilepticus. They had epilepsy,
      they were on chronic anticonvulsants (ACVs), and some had other neurological
      deficits. All received intravenous and/or rectal ACVs prior to suspicion of PSE.
      PSE was confirmed via video/EEG, demonstrating no epileptogenic activity during
      alleged seizures. Provocation and placebo therapy techniques were used in two.
      Psychiatric assessment identified comorbid disorders such as depression, anxiety
      disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, and
      posttraumatic stress disorder. Psychosocial stressors were almost ubiquitous.
      Psychiatric intervention included psychotherapy, family therapy, and medical
      treatment in one patient. Outcome was monitored for an average of 3.6 years (3-5
      years). PSE did not recur. PSs recurred in three. Psychiatric comorbidity
      improved in four, who accepted psychiatric intervention and whose epilepsy also
      improved. In conclusion, the occurrence of PSE in children and adolescents with
      epilepsy is stressed. Prompt diagnosis was often missed in the acute care
      setting, and this carries important implications for iatrogenic complications.
      PSE diagnosis resulted in identification and management of comorbid psychiatric
      disorders. This was probably important in reducing the predominating anxiety and
      affective disorders in most patients as well as PSE recurrence. Epilepsy severity
      and associated deficits were most likely important factors in determining
      outcome.

PMID- 15256193
TI  - Taking charge of epilepsy: the development of a structured psychoeducational
      group intervention for adolescents with epilepsy and their parents.
AB  - Children and adolescents with epilepsy frequently experience poor psychosocial
      outcomes due to numerous factors such as perceived stigma, behavior problems,
      academic difficulties, and depression. Health psychology research has documented
      the effectiveness of psychoeducational interventions aimed at improving
      psychosocial outcomes for individuals with a variety of health conditions. With
      increasing numbers of adolescents living with epilepsy, interest in improving the
      quality of life for this particular population has grown. There remains, however,
      a paucity of research concerning psychosocial interventions for adolescents with
      epilepsy. The present study outlines the development and initial implementation
      of a 6-week structured psychoeducational group intervention for adolescents with
      epilepsy and their parents. Preintervention, the QOLIE-AD-48, Childhood
      Depression Inventory, and Revised Children's Manifest Anxiety Scale were
      administered. Educational topics included medical aspects of epilepsy, healthy
      lifestyle behaviors, family and peer relationships, understanding self-image and
      self-esteem, and stress management techniques. Participants were introduced to a
      variety of cognitive-behavioral strategies, and were encouraged to share their
      own experiences with epilepsy. Feedback from adolescent and parent participants
      indicated that the intervention was relevant to their needs, helped them better
      understand their epilepsy, and allowed an opportunity for positive peer support.
      Also, postintervention outcome measurement indicated an overall positive trend
      for quality of life improvement in the adolescents.

PMID- 15256194
TI  - Maternal adaptation to a child's epilepsy.
AB  - Mothers of children with epilepsy are at risk for problems in adapting to their
      child's condition; however, factors associated with maternal adaptation to a
      child's epilepsy have not been well articulated. The purpose of this study was to
      investigate the associations among maternal and child characteristics, maternal
      beliefs, and maternal adaptation outcomes. A conceptual model was formulated
      based on the literature. Maternal beliefs were proposed to mediate the
      relationships between maternal and child characteristics and maternal adaptation
      outcomes. A sample of 156 maternal-child dyads provided data via structured
      telephone interviews. Multiple regression analysis was used to test for additive
      and mediated relationships. Mediation was not supported statistically. Child
      behavior problems, maternal satisfaction with family, and maternal learned
      helplessness had the strongest associations with maternal outcomes, suggesting
      that maternal adaptation to a child's epilepsy is complex and includes multiple
      factors in addition to the child's seizure condition.

PMID- 15256195
TI  - Obsessive-compulsive symptoms in patients with temporal lobe epilepsy.
AB  - The goals of this work were to: (1) determine the prevalence of clinically
      significant obsessive-compulsive (OC) symptoms in patients with temporal lobe
      epilepsy (TLE), (2) characterize the differences in self-reported OC symptoms in
      patients with TLE and a normative control group, and (3) compare the severity of
      OC symptoms in right and left hemisphere TLE patients. Patients with TLE (n=30)
      were administered the Obsessive-Compulsive Inventory (OCI). As a group, patients
      with TLE had a higher prevalence of OC symptoms than the nonpatient normative
      sample. In addition, TLE patients exhibited elevated scores on all but 3 of the
      16 OCI scales and subscales. There were no reliable differences in OC symptoms in
      patients with right versus left hemisphere seizure foci, although the right
      hemisphere patients tended to score higher on both scales of the OCI.

PMID- 15256196
TI  - Self-report of cognitive abilities in temporal lobe epilepsy: cognitive,
      psychosocial, and emotional factors.
AB  - Self-report of cognitive functioning using the Multiple Abilities Self-Report
      Questionnaire (MASQ) was examined in 57 left (LTLE) and 36 right (RTLE) temporal
      lobe epilepsy patients. The MASQ is a 38-item self-report measure assessing five
      domains of self-perceived cognitive functioning: Language, Visual-Perceptual
      Abilities, Verbal Memory, Visual-Spatial Memory, and Attention/Concentration.
      Overall, LTLE patients self-reported more cognitive difficulties across all
      domains. Language was the only domain to emerge as a robust indicator of seizure
      lateralization (LTLE patients reporting more problems). Neuropsychological test
      performance did not emerge as a significant predictor for any domain, whereas
      measures of psychosocial and emotional functioning accounted for a significant
      but modest amount of variance in all of them. The results suggest caution in
      using such self-report measures as an ecological extension of objective testing,
      but suggest a role in assessing self-appraisal of deficits.

PMID- 15256198
TI  - Group psychoeducation as treatment for psychological nonepileptic seizures.
AB  - There is no consensus for the type(s) of treatment(s) that may be effective or
      ineffective for psychological nonepileptic seizures (PNES). We provided an open
      ended group psychotherapy program to 10 patients with PNES, including a disorder
      specific psychoeducation treatment component in the first 10 weeks. Seizure
      frequency and questionnaire responses were examined pre- and posttreatment in all
      7 of 10 individuals who completed the majority of the psychoeducational sessions.
      Four individuals experienced no change in seizure frequency; in three of these
      this was due to a cessation of events at treatment initiation. Two individuals
      experienced a decline; and one, an increase, in seizure frequency. Significant
      decreases were reported in posttraumatic (P=0.003) and dissociative (P=0.04)
      symptoms and emotionally based coping mechanisms (P=0.03). There was also a trend
      toward improved quality of life (P=0.07). Experience/expression of anger remained
      stable. Psychoeducation may be an effective method of treating PNES and may
      improve coping strategies and reduce PNES-associated psychopathology in some
      patients. Additional controlled studies on larger samples are needed.

PMID- 15256197
TI  - Treatments and perceptions of epilepsy in Kashmir and the United States: a cross
      cultural analysis.
AB  - Treatments and perceptions of epilepsy have been found to vary across cultures.
      This study draws on a comparison of two patient samples, one from the United
      States (n=28), the other from Kashmir (n=29), to gauge the similarities and
      differences in social perceptions of epilepsy, attitudes toward conventional and
      alternative treatments, practice of conventional and alternative treatments, and
      selected quality-of-life issues. While both the Kashmiri and American patients
      interviewed were prescribed a similar regimen of traditional antiepileptic drugs,
      a wider range of drugs and treatments were available to and used by the latter.
      The use of adjunctive spiritual therapies was more prevalent in the Kashmiri
      sample, and the use of alternative, nonpharmacological therapies was more
      prevalent in the American sample. Quality of life for the Kashmiri patients
      sampled was found to be poorer in terms of educational and occupational
      opportunities, feelings of stigmatization, and openness with others about the
      illness. Although the two patient populations interviewed differed in their
      access to resources and approaches to the disorder, both samples were found to be
      similar overall in many attitudes and practices relating to epilepsy and its
      treatment.

PMID- 15256199
TI  - Risk of aspiration pneumonia after an epileptic seizure: a retrospective analysis
      of 1634 adult patients.
AB  - We reviewed the incidence of aspiration pneumonia secondary to seizures in three
      populations of patients with chronic epilepsy: 733 outpatients seen in an
      Epilepsy Foundation clinic; 806 adult patients admitted to two university video
      telemetry units; and 95 institutionalized, profoundly retarded adult patients
      with chronic epilepsy. Two of the 733 adults who had seizures in the outpatient
      setting and 2 of the 806 patients who had one or more epileptic seizures in the
      telemetry units developed aspiration pneumonia. In the 95 institutionalized
      patients, there were 17 instances of aspiration pneumonia after a generalized
      seizure and 32 instances of aspiration unrelated to seizures over a 12-month
      period. Our findings suggest that aspiration pneumonia is not a common
      complication of seizures in otherwise healthy adults. The increased incidence of
      aspiration in developmentally delayed individuals seems to derive from a
      combination of factors. Increased oral secretions, impaired swallowing
      mechanisms, and difficulty in attaining adequate patient positioning
      significantly increased the risk of aspiration.

PMID- 15256200
TI  - The influence of the full moon on seizure frequency: myth or reality?
AB  - To investigate a possible relationship between seizure frequency and the lunar
      cycle, we reviewed the occurrence of seizures recorded in our epilepsy monitoring
      unit over a 3-year period. Analysis of the total number of seizures (epileptic
      plus nonepileptic) showed no significant association. A separate analysis
      revealed that for nonepileptic seizures, there was an increase at the full moon,
      and for epileptic seizures, an increase in the last quarter. We conclude that
      there is no "full moon" effect on seizures as a whole, although there is a
      possible effect on nonepileptic seizures.

PMID- 15256201
TI  - The sudden death of Patsy Custis, or George Washington on sudden unexplained
      death in epilepsy.
AB  - Patsy Custis, George Washington's stepdaughter, died suddenly during a brief
      seizure in 1773. Accounts of Patsy's illness and unexpected death were abstracted
      from George Washington's papers available via the Library of Congress. Patsy's
      epilepsy, the treatments she received, and his descriptions of her death were
      studied. Sudden unexplained death in epilepsy (SUDEP) criteria are applied and
      discussed. George Washington's description of Patsy's epilepsy and subsequent
      death meet criteria for SUDEP.

PMID- 15256202
TI  - Commentary on "Personality changes following temporal lobectomy for epilepsy".

PMID- 15256203
TI  - Personality changes following temporal lobectomy for epilepsy. 1957.

PMID- 15256204
TI  - On the need for battery replacement before end of service in vagus nerve
      stimulation for epilepsy.

PMID- 15256207
TI  - Mapping phenotypic landscapes using DNA micro-arrays.
AB  - Inverse metabolic engineering is a useful approach for engineering phenotypes in
      biological systems. The overarching objective of this approach is to combine the
      power of evolutionary engineering approaches with the precision of constructive
      metabolic engineering strategies. Often the difficulty in this approach is
      elucidating the genetic basis of the phenotypes that emerge as a result of
      evolutionary mechanisms. As a result of advances in genomics technologies,
      several techniques now exist that substantially improve researchers ability to
      identify such genes. Metabolic engineers now have the ability to map phenotypic
      landscapes of considerable genetic diversity, which should improve understanding
      of the relationships that exist among phenotype, genotype, and environment. In
      this mini-review, we will discuss several of such genomics tools that may be
      useful in developing inverse metabolic engineering strategies and, in particular,
      mapping phenotypic landscapes.

PMID- 15256208
TI  - Reverse engineering of industrial pharmaceutical-producing actinomycete strains
      using DNA microarrays.
AB  - Transcript levels in production cultures of wildtype and classically improved
      strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces
      fradiae were monitored using microarrays of the sequenced actinomycete S.
      coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics
      erythromycin and tylosin, respectively, and the classically improved strains
      contain unknown overproduction mutations. The Sac. erythraea overproducer was
      found to express the entire 56-kb erythromycin gene cluster several days longer
      than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer
      strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while
      they expressed several tens of other S. fradiae genes and S. coelicolor homologs
      differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor
      isobutyryl-CoA mutase homolog icmA. These observations indicated that
      overproduction mechanisms in classically improved strains can affect both the
      timing and rate of antibiotic synthesis, and alter the regulation of antibiotic
      biosynthetic enzymes and enzymes involved in precursor metabolism.

PMID- 15256209
TI  - Amino acid stabilization for cell-free protein synthesis by modification of the
      Escherichia coli genome.
AB  - Cell-free biology provides a unique opportunity to assess and to manipulate
      microbial systems by inverse metabolic engineering. We have applied this approach
      to amino acid metabolism, one of the systems in cell-free biology that limits
      protein synthesis reactions. Four amino acids (arginine, tryptophan, serine and
      cysteine) are depleted during a 3-h batch cell-free protein synthesis reaction
      under various conditions. By modifying the genome of the Escherichia coli strain
      used to make the cell extract, we see significant stabilization of arginine,
      tryptophan and serine. Cysteine, however, continues to be degraded. Cell-free
      protein synthesis with the modified cell extract produces increased yields of the
      cysteine-free protein Outer Membrane Protein T (OmpT).

PMID- 15256210
TI  - Impact of 'ome' analyses on inverse metabolic engineering.
AB  - Genome-wide or large-scale methodologies employed in functional genomics such as
      DNA sequencing, transcription profiling, proteomics, and metabolite profiling
      have become important tools in many metabolic engineering strategies. These
      techniques allow the identification of genetic differences and insight into their
      cellular effects. In the field of inverse metabolic engineering mapping of
      differences between strains with different degree of a certain desired phenotype
      and subsequent identification of factors conferring that phenotype are an
      essential part. Therefore, the tools of functional genomics in particular have
      the potential to promote and expand inverse metabolic engineering. Here, we
      review the use of functional genomics methods in inverse metabolic engineering,
      examples are presented, and we discuss the identification of targets for
      metabolic engineering with low fold changes using these techniques.

PMID- 15256211
TI  - Assaying gene function by growth competition experiment.
AB  - High-throughput screening and analysis is one of the emerging paradigms in
      biotechnology. In particular, high-throughput methods are essential in the field
      of functional genomics because of the vast amount of data generated in recent and
      ongoing genome sequencing efforts. In this report we discuss integrated
      functional analysis methodologies which incorporate both a growth competition
      component and a highly parallel assay used to quantify results of the growth
      competition. Several applications of the two most widely used technologies in the
      field, i.e., transposon mutagenesis and deletion strain library growth
      competition, and individual applications of several developing or less widely
      reported technologies are presented.

PMID- 15256212
TI  - Inverse metabolic engineering with phosphagen kinase systems improves the
      cellular energy state.
AB  - Inverse metabolic engineering attempts to identify or construct desired
      phenotypes of applied interest to endow them on appropriate host organisms. A
      particular desirable phenotype is the ATP homeostasis exhibited by animal cells
      with high and variable ATP turnover through temporal and spatial energy
      buffering. This buffering is achieved by phosphagen kinase systems that consist
      of a specific kinase and its cognate phosphagen, which functions as a large pool
      of 'high-energy phosphates' that are used to replenish ATP during periods of high
      energetic demand. This review discusses recent advances and potentials of inverse
      metabolic engineering of cell types that do not normally contain such systems-
      bacteria, yeast, plants, and liver--with creatine or arginine kinase systems.
      Examples are discussed that illustrate how microbial metabolism can be tailored
      for large-scale industrial processes with imperfect mixing and how the liver can
      be protected from metabolic insults or stimulated for better regeneration.

PMID- 15256213
TI  - Stoichiometric network constraints on xylose metabolism by recombinant
      Saccharomyces cerevisiae.
AB  - Metabolic pathway engineering is constrained by the thermodynamic and
      stoichiometric feasibility of enzymatic activities of introduced genes.
      Engineering of xylose metabolism in Saccharomyces cerevisiae has focused on
      introducing genes for the initial xylose assimilation steps from Pichia stipitis,
      a xylose-fermenting yeast, into S. cerevisiae, a yeast traditionally used in
      ethanol production from hexose. However, recombinant S. cerevisiae created in
      several laboratories have used xylose oxidatively rather than in the fermentative
      manner that this yeast metabolizes glucose. To understand the differences between
      glucose and engineered xylose metabolic networks, we performed a flux balance
      analysis (FBA) and calculated extreme pathways using a stoichiometric model that
      describes the biochemistry of yeast cell growth. FBA predicted that the ethanol
      yield from xylose exhibits a maximum under oxygen-limited conditions, and a
      fermentation experiment confirmed this finding. Fermentation results were largely
      consistent with in silico phenotypes based on calculated extreme pathways, which
      displayed several phases of metabolic phenotype with respect to oxygen
      availability from anaerobic to aerobic conditions. However, in contrast to the
      model prediction, xylitol production continued even after the optimum aeration
      level for ethanol production was attained. These results suggest that oxygen (or
      some other electron accepting system) is required to resolve the redox imbalance
      caused by cofactor difference between xylose reductase and xylitol dehydrogenase,
      and that other factors limit glycolytic flux when xylose is the sole carbon
      source.

PMID- 15256214
TI  - Alternative pathways of galactose assimilation: could inverse metabolic
      engineering provide an alternative to galactosemic patients?
AB  - The galactose assimilation pathway has been extensively studied as an example of
      a genetic regulatory switch. Besides the importance of this pathway as a tool in
      basic biological research, unraveling its structure and regulation is also of
      major medical importance. Impairment of galactose assimilation is the cause of
      the genetic metabolic disease known as "galactosemia", while the in vivo activity
      of the pathway affects the production of glycans. The latter have been connected
      to tumor metastasis, anti-cancer drug resistance and various cardiovascular
      diseases. Despite the vast amount of studies, however, galactose assimilation and
      its interaction with other parts of the metabolic network have not been fully
      elucidated yet. In yeast and higher eukaryotes, it is still being studied as
      comprising only the linear Leloir pathway. Recent observations, however, indicate
      that alternative pathways of galactose assimilation identified in prokaryotes and
      fungi might also be present in yeast. Such a result is valuable per se, because
      it could lead to the discovery of these pathways in humans. Even more
      importantly, these pathways provide alternative phenotypes with known genetic
      fingerprints that can be used in the context of classical and inverse metabolic
      engineering to examine and treat the mechanisms of defects of galactose
      assimilation.

PMID- 15256215
TI  - The pathways and molecular mechanisms regulating Nrf2 activation in response to
      chemical stress.
AB  - The induction of many antioxidant and phase II drug-metabolizing enzymes by
      phenolic antioxidants and electrophilic compounds is regulated at the
      transcriptional level. The response to these compounds is mediated by the cis
      acting antioxidant response element (ARE) found in the promoter of the encoding
      genes. The transcription factor NF-E2-related factor 2, or Nrf2, has emerged as
      the central protein that binds to the ARE to activate gene transcription. Data
      from many studies indicate that Nrf2 is constitutively and ubiquitously expressed
      in a number of tissues and cell lines and is thus responsible for the low-level
      expression of its target genes observed under physiological conditions. However,
      in cells exposed to oxidative stress, Nrf2 activity is increased, further driving
      the transcriptional activation of genes whose expression is essential to control
      cellular redox homeostasis. Recent studies suggest that the activation of Nrf2
      involves a coordinated process and is regulated at multiple levels. Nrf2 activity
      is believed to be repressed through the binding of the cytoskeleton-associated
      protein Keap1, and its activation involves mechanisms that interfere with this
      interaction. Activation of Nrf2 has also been demonstrated to be dependent on
      mechanisms that mediate its stabilization. In this review, the mechanisms
      controlling this activation process as reported in recent studies will be
      examined and discussed, with particular emphasis on those affecting Nrf2
      stability at the molecular level.

PMID- 15256216
TI  - S-Nitrosohemoglobin: an allosteric mediator of NO group function in mammalian
      vasculature.
AB  - Since the discovery of NO as the endothelium-derived relaxing factor, there has
      been considerable interest in how NO interacts with hemoglobin (Hb). Numerous
      investigations have highlighted the possibility that rather than operating as a
      sink to consume NO, the vasculature can operate as a delivery mechanism for NO.
      The principal hypothesis proposed to explain this phenomenon is that Hb can
      transport NO on the conserved cysteine residue beta93 and deliver that NO to the
      tissues in an allosterically dependent manner. This proposal has been termed the
      S-Nitrosohemoglobin (SNO-Hb) Hypothesis. This review addresses the experimental
      evidence that led to development of this hypothesis and examines much of the
      research that resulted from its generation. Specifically it covers the evidence
      concerning NO in the vasculature, the SNO-Hb Hypothesis itself, the biochemical
      and biophysical data relating to NO and Hb interactions, SNO-Hb in human
      physiology, and alternative vascular forms of NO. Finally a model of NO in the
      vasculature in which SNO-Hb forms the central core is proposed.

PMID- 15256217
TI  - Multiple oxidative stress-response members of the Adapt78 family.
AB  - Adapt78 is an oxidative and calcium stress-response gene. Its protein product is
      a potent natural inhibitor of the intracellular calcium signaling protein
      calcineurin. Much of what is known about Adapt78 protein is based on cell
      transfection studies. Toward understanding natural endogenous Adapt78, we used an
      antibody raised against cellular Adapt78 and recently determined that endogenous
      Adapt78 protein, like its mRNA, is oxidative and calcium stress responsive. Here
      we report the identification of a second endogenous form of this protein family
      of 41 kDa. Subcellular fractionation of human HeLa cells revealed that in
      contrast to results of previous transfection studies, most endogenous Adapt78,
      characterized as 29 and 41 kDa electrophoretic doublets, resides in the cellular
      cytosol. The 41 kDa form of Adapt78 was abundant and found to exhibit many
      characteristics in common with the previously reported oxidative stress
      responsive 29 kDa form, including hypo- and hyperphosphorylation variants, rapid
      loss of the hypophosphorylated form following oxidative stress, response to
      various kinase and phosphatase inhibitors, and localization. However, it also
      exhibited some unique characteristics, most notably the lack of calcium
      inducibility. Finally, the 29 kDa form exhibited a much shorter half-life and
      strong stabilization following oxidant exposure compared with the 41 kDa Adapt78
      form. These data reveal the presence of a novel oxidative stress-responsive 41
      kDa Adapt78 species, lend further insight into the Adapt78 family of proteins and
      their distribution, and challenge previous conclusions obtained using
      transfection protocols.

PMID- 15256218
TI  - Combined action of extracellular signal-regulated kinase and p38 kinase rescues
      Molt4 T cells from nitric oxide-induced apoptotic and necrotic cell death.
AB  - The mechanisms that regulate nitric oxide (NO)-induced apoptosis, especially in T
      cell apoptosis, are largely uncharacterized. Here, we report that protection from
      NO-induced cell death by phorbol 12-myristate 13-acetate (PMA) is dependent on
      both p38 and extracellular signal-regulated kinase (ERK) activation. Exposure of
      Molt4 cells to NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced both
      apoptotic and necrotic modes of cell death along with a sustained increase in p38
      kinase phosphorylation. However, the p38 inhibitor SB202190 only slightly
      protected Molt4 cells from NO toxicity. In contrast, PMA rapidly phosphorylated
      both p38 kinase and ERK, and the phosphorylation statuses were not altered in the
      presence of SNAP. Interestingly, although each mitogen-activated protein kinase
      (MAPK) inhibitor by itself had only a modest effect, the combination of
      inhibitors for both MAPKs almost completely abolished the protective effect of
      PMA. Furthermore, dominant negative or catalytically inactive variants that
      modulate p38 and ERK mimicked the effects of MAPK inhibitors. We located the
      action of p38 and ERK upstream of the p53/mitochondrial membrane potential loss
      and caspases cascade. Together, these findings suggest that the PMA-induced
      activations of ERK and p38 kinase are parallel events that are both required for
      inhibition of NO-induced death of Molt4 cells.

PMID- 15256219
TI  - Oxidative stress and delayed-onset muscle damage after exercise.
AB  - Reactive oxygen species (ROS) produced during exercise may be involved in delayed
      onset muscle damage related to inflammation. To investigate this hypothesis, we
      studied whether oxidative stress increases nuclear translocation of nuclear
      factor-kappaB and chemokine expression in skeletal muscle using myotube L6 cells.
      We also assessed whether prolonged acute exercise could increase these parameters
      in rats. In L6 cells, H(2)O(2) induced nuclear translocation of p65 and increased
      the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and
      monocyte chemoattractant protein-1 (MCP-1), whereas preincubation with alpha
      tocopherol limited the increase in these proteins. Sprague Dawley rats were
      divided into the following groups: rested control, exercised, rested with a high
      alpha-tocopherol diet, and exercised with a high alpha-tocopherol diet. After 3
      weeks of acclimation, both exercise groups ran on a treadmill at 25 m/min for 60
      min. Exercise increased nuclear p65, CINC-1, and MCP-1 in gastrocnemius muscle
      cells, but these changes were ameliorated by the high alpha-tocopherol diet.
      Increases in myeloperoxidase and thiobarbituric acid-reactive substrates were
      ameliorated by a high alpha-tocopherol diet, as were the histological changes.
      Neutrophil activity was not altered by either exercise or a high alpha-tocopherol
      diet. These results indicate that delayed-onset muscle damage induced by
      prolonged exercise is partly related to inflammation via phagocyte infiltration
      caused by ROS and that alpha-tocopherol (an antioxidant) can attenuate such
      inflammatory changes.

PMID- 15256220
TI  - Are endogenous clustered DNA damages induced in human cells?
AB  - Although clustered DNA damages are induced in cells by ionizing radiation and can
      be induced artifactually during DNA isolation, it was not known if they are
      formed in unirradiated cells by normal oxidative metabolism. Using high
      sensitivity methods of quantitative gel electrophoresis, electronic imaging, and
      number average length analysis, we found that two radiosensitive human cell lines
      (TK6 and WI-L2-NS) accumulated Fpg-oxidized purine clusters and Nth-oxidized
      pyrimidine clusters but not Nfo-abasic clusters. However, four repair-proficient
      human lines (MOLT 4, HL-60, WTK1, and 28SC) did not contain significant levels
      (<5/Gbp) of any cluster type. Cluster levels were independent of p53 status.
      Measurement of glycosylase levels in 28SC, TK6, and WI-L2-NS cells suggested that
      depressed hOGG1 and hNth activities in TK6 and WI-L2-NS could be related to
      oxybase cluster accumulation. Thus, individuals with DNA repair enzyme
      deficiencies could accumulate potentially cytotoxic and mutagenic clustered DNA
      damages. The absence of Nfo-detected endogenous clusters in any cells examined
      suggests that abasic clusters could be a signature of cellular ionizing radiation
      exposure.

PMID- 15256221
TI  - Melatonin does not prevent the protection of ischemic preconditioning in vivo
      despite its antioxidant effect against oxidative stress.
AB  - Free radicals are involved in the protective mechanism of preconditioning (PC),
      whereas antioxidant compounds abolish this benefit. Melatonin is a hormone with
      antioxidant properties. The aim of our study was to evaluate the effect of
      melatonin on infarct size in ischemic preconditioning in vivo. We randomly
      divided 33 male rabbits into four groups and subjected them to 30 min of
      myocardial ischemia and 3 h of reperfusion with the following prior
      interventions: (i) no intervention, (ii) iv melatonin at a total dose of 50
      mg/kg, (iii) PC with two cycles of 5 min ischemia and 10 min reperfusion, and
      (iv) combined melatonin and PC. In a second series of experiments, another
      antioxidant agent N-acetylcysteine (NAC) was used in a control and in a PC group.
      Myocardial infarct size was determined and blood samples were drawn at different
      time points for the determination of lipid peroxidation products, total
      superoxide dismutase (SOD) activity, and (1)H-NMR spectra to evaluate the changes
      in the metabolic profile. Melatonin showed no effect on myocardial infarct size
      in the group of sustained ischemia (42.9 +/- 3.6% vs 47.4 +/- 4.9%) and it did
      not attenuate the reduction of myocardial infarct size in the PC group (13.6 +/-
      2.4% vs 14.0 +/- 1.7%). A similar effect was found in NAC-treated groups (44.8 +/
      3.4% vs 14.3 +/- 1.3%). Lipid peroxidation product levels were significantly
      elevated in the control and PC groups, whereas melatonin decreased them in both
      groups. The SOD activity was enhanced in the PC group compared to controls;
      melatonin kept SOD activity unchanged during ischemia/reperfusion and enhanced
      its activity when it was combined with PC. Melatonin did not change the metabolic
      profile of the control and PC groups. Melatonin does not prevent the beneficial
      effect of ischemic PC on infarct size despite its antioxidant properties.

PMID- 15256222
TI  - Ascorbate distribution during hibernation is independent of ascorbate redox
      state.
AB  - Distribution of ascorbate into tissues is an essential process in ascorbate
      antioxidant defense. Hibernating animals are studied as a model of tolerance to
      ischemia-reperfusion because of their tolerance to fluctuations in blood flow
      associated with prolonged torpor and periodic arousal episodes. Throughout
      hibernation, plasma ascorbate concentration ([Asc](p)) repetitively increases
      during torpor, then falls during periodic arousal bouts. We previously proposed
      that high [Asc](p) provides a ready source of antioxidant protection for
      distribution to the central nervous system and peripheral tissues during arousal.
      Here we tested whether deliberate oxidation of plasma ascorbate by intravenous
      administration of ascorbate oxidase (AO), prior to arousal, compromised tissue
      levels of ascorbate or the other water-soluble antioxidants, glutathione (GSH)
      and urate. Although AO decreased [Asc](p) to below the level of detection during
      torpor and after arousal, ascorbate oxidation did not decrease post-arousal
      tissue levels of reduced ascorbate, glutathione, or urate in any tissue examined,
      except liver. The data imply that ascorbate is taken up equally well into brain
      and other tissues as either ascorbate or its oxidized product dehydroascorbate,
      with subsequent intracellular reduction of dehydroascorbate. Lack of effect of
      ascorbate oxidation on tissue levels of GSH or urate indicates that
      dehydroascorbate uptake and reduction do not compromise tissue concentrations of
      these other water-soluble antioxidants. Thus, we show equal availability of
      reduced and oxidized plasma ascorbate during metabolically demanding
      thermogenesis and reperfusion associated with arousal from hibernation.

PMID- 15256223
TI  - The RING-H2-finger protein APC11 as a target of hydrogen peroxide.
AB  - The anaphase-promoting complex (APC) is a ubiquitin-protein ligase (E3) that
      targets cell cycle regulators such as cyclin B and securin for degradation. The
      APC11 subunit functions as the catalytic core of this complex and mediates the
      transfer of ubiquitin from a ubiquitin-conjugating enzyme (E2) to the substrate.
      APC11 contains a RING-H2-finger domain, which includes one histidine and seven
      cysteine residues that coordinate two Zn(2+) ions. We now show that exposure of
      purified APC11 to H(2)O(2) (0.1 to 1 mM) induced the release of bound zinc as a
      result of the oxidation of cysteine residues. It also impaired the physical
      interaction between APC11 and the E2 enzyme Ubc4 as well as inhibited the
      ubiquitination of cyclin B1 by APC11. The release of HeLa cells from metaphase
      arrest in the presence of exogenous H(2)O(2) inhibited the ubiquitination of
      cyclin B1 as well as the degradation of cyclin B1 and securin that were apparent
      in the absence of H(2)O(2). The presence of H(2)O(2) also blocked the co
      immunoprecipitation of Ubc4 with APC11 and delayed the exit of cells from
      mitosis. Inhibition of APC11 function by H(2)O(2) thus likely contributes to the
      delay in cell cycle progression through mitosis that is characteristic of cells
      subjected to oxidative stress.

PMID- 15256224
TI  - Effect of hydrogen peroxide on reoxygenation-induced Ca2+ accumulation in rat
      cardiomyocytes.
AB  - Reactive oxygen species (ROS) contribute to cell damage during reperfusion of the
      heart. ROS may exert their effects partly by interfering with Ca(2+) homeostasis
      of the myocardium. The purpose of this study was to investigate the effects of
      hydrogen peroxide (H(2)O(2)) on Ca(2+) accumulation during reoxygenation of
      isolated adult rat cardiomyocytes exposed to 1 h of hypoxia and to relate the
      effects to possible changes in release of lactate dehydrogenase (LDH), free
      intracellular Ca(2+) ([Ca(2+)](i)) and Mg(2+)([Mg(2+)](i)), and mitochondrial
      membrane potential (Deltapsim). Cell Ca(2+) was determined by (45)Ca(2+) uptake.
      Free [Mg(2+)](i) and [Ca(2+)](i) and Deltapsim were measured by flow cytometry.
      Reoxygenation-induced Ca(2+) accumulation was attenuated by 23 and 34% by 10 and
      25 microM H(2)O(2), respectively, added at reoxygenation. H(2)O(2) at 100 and 250
      microM increased cell Ca(2+) by 50 and 83%, respectively, whereas 500 microM
      H(2)O(2) decreased cell Ca(2+) by 20%. H(2)O(2) at (25 microM) reduced LDH
      release and [Mg(2+)](i) and increased Deltapsim, indicating cell protection,
      whereas 250 microM H(2)O(2) increased LDH release and [Mg(2+)](i) and decreased
      Deltapsim, indicating cell damage. Clonazepam (100 microM) attenuated the
      increase in Ca(2+) accumulation, the elevation of [Ca(2+)](i), and the decrease
      in Deltapsim induced by 100 and 250 microM H(2)O(2) during reoxygenation. We
      report for the first time that 25 microM H(2)O(2) attenuates Ca(2+) accumulation,
      LDH release, and dissipation of Deltapsim during reoxygenation of hypoxic
      cardiomyocytes, indicating cell protection.

PMID- 15256225
TI  - Induction of endothelial iNOS by 4-hydroxyhexenal through NF-kappaB activation.
AB  - Lipid peroxidation and its end-product, 4-hydroxyhexenal (HHE), are known to
      affect redox balance during aging, which causes various degenerative processes
      including vascular alterations from endothelial cell deterioration. To better
      understand the molecular action of HHE in the development of vascular
      abnormalities during the aging process, we investigated whether the upregulation
      of inducible endothelial nitric oxide synthase (iNOS) by HHE is mediated through
      nuclear factor kappaB (NF-kappaB) activation. Results indicate that HHE
      stimulates iNOS by the transcriptional regulation of NF-kappaB activation through
      cytosolic kappaB degradation inhibitors (IkappaB). Pretreatment with NF-kappaB
      inhibitors Bay 11-7082 and N-acetyl cysteine (NAC) suppressed the upregulation of
      iNOS by blunting IkappaB degradation and NF-kappaB binding activity. Because
      inflammatory stimuli induce iNOS to generate large amounts of nitric oxide (NO),
      intracellular NO levels in the presence of Bay 11-7082, NAC, and caffeic acid
      methyl ester were estimated. These inhibitors significantly suppressed the HHE
      induced NO levels to a basal level. These findings strongly suggest that in
      endothelial cells, HHE induces iNOS gene expression through NF-kappaB activation,
      which can lead to vascular dysfunction by the activation of various
      proinflammatory genes.

PMID- 15256226
TI  - Kinetics of the reaction between nitric oxide and glutathione: implications for
      thiol depletion in cells.
AB  - Nitric oxide in the absence of oxygen was suggested to react with 5-50 mM
      glutathione (GSH) over many minutes when [NO*] << [GSH] (N. Hogg et al., FEBS
      Lett. 382:223-228; 1996). However, Aravindakumar et al. (J. Chem. Soc. Perkin
      Trans. 2:663-669; 2002) provided data suggesting approximately 200-fold higher
      reactivity under conditions of [NO*] >> [GSH]. To help resolve these differences,
      the rate of loss of NO* ( approximately 9 microM) in aqueous solutions of GSH
      (2.5-20 mM) was measured by chemiluminescence. An apparent second-order rate
      constant of 0.080 +/- 0.008 M(-1) s(-1) at pH 7.4, 37 degrees C, was calculated
      based on the total [GSH] and "pseudo-first-order" kinetics; thiolate anion was
      much more reactive than undissociated thiol. These data imply a half-life of
      approximately 30 min for low concentrations of NO* with 5 mM GSH, 37 degrees C,
      pH 7.4, in the absence of oxygen. Possible kinetic schemes that can partially
      explain the divergent literature reports are discussed, notably an equilibrium in
      the reaction between NO* and GSH. Human breast carcinoma MCF-7 cells were exposed
      to NO* (initially approximately 18 microM) in alidded six well plate in an
      anaerobic chamber in vitro; intracellular GSH levels decreased by half in
      approximately 60 min. Aerobic exposure depletes GSH in cells in vitro much faster
      because of autoxidation of NO* to NO2*, >10(8) times more reactive toward GSH.

PMID- 15256228
TI  - Guidance on the publication of guidelines.

PMID- 15256227
TI  - A comprehensive study of oxidative stress and antioxidant status in preeclampsia
      and normal pregnancy.
AB  - Oxidative stress has been increasingly postulated as a major contributor to
      endothelial dysfunction in preeclampsia (PE), although evidence supporting this
      hypothesis remains inconsistent. This study aimed to analyze in depth the
      potential role of oxidative stress as a mechanism underlying endothelial damage
      in PE and the pregnant woman's susceptibility to the disease. To this end,
      indicative markers of lipoperoxidation and protein oxidation and changes in
      antioxidant defense systems were measured in blood samples from 53 women with PE
      and 30 healthy pregnant controls. Results, analyzed in relation to disease
      severity, showed PE women, compared with women with normal pregnancy, to have:
      (1) significantly enhanced antioxidant enzyme SOD and GPx activities in
      erythrocytes; (2) similar plasma alpha-tocopherol levels and significantly
      increased alpha-tocopherol/lipids in both mild and severe PE; (3) significantly
      decreased plasma vitamin C and protein thiol levels; (4) similar erythrocyte
      glutathione content, total plasma antioxidant capacity, and whole plasma
      oxidizability values; (5) significantly elevated plasma total lipid
      hydroperoxides, the major initial reaction products of lipid peroxidation, in
      severe PE; (6) no intracellular or extracellular increases in any of the
      secondary end-products of lipid peroxidation, malondialdehyde or lipoperoxides;
      (7) similar oxidative damage to proteins quantified by plasma carbonyl levels,
      immunoblot analysis, and advanced oxidation protein products assessment; and (8)
      significantly elevated and severity-related soluble vascular cell adhesion
      molecule-1 serum levels reflecting endothelial dysfunction. No correlations were
      found among plasma levels of circulating adhesion molecules with regard to lipid
      and protein oxidation markers. Globally, these data reflect mild oxidative stress
      in blood of preeclamptic women, as oxidative processes seem to be counteracted by
      the physiologic activation of antioxidant enzymes and by the high plasma vitamin
      E levels that would prevent further oxidative damage. These results do not permit
      us to conclude that oxidative stress might be a pathogenetically relevant process
      causally contributing to the disease.

PMID- 15256229
TI  - Metastases to the thyroid gland: the Royal Marsden experience.
AB  - AIM: A review of patients seen at the Royal Marsden Hospital with metastases to
      the thyroid gland. METHOD: Experience reported on 15 patients that were seen at
      our institution between 1985 and 2002. RESULTS: The most common site of origin
      was the kidney (4/15). Ages ranged between 26 and 76 years. Twelve presented with
      a neck mass. Most had metastatic disease elsewhere at the time of presentation
      (9/15). Diagnosis was made by fine needle aspiration cytology (5), tru-cut biopsy
      (1), or surgery (9); surgery comprised total thyroidectomy (3), subtotal
      thyroidectomy (3) or lobectomy (3). Radiotherapy resulted in disease
      stabilisation in three patients. Chemotherapy was used to treat local recurrence
      in two patients post-operatively. The interval from diagnosis of the primary
      tumour to thyroid metastasis varied from 0 months to 15 years. Thyroid gland
      metastasis was the initial manifestation of metastatic disease in five patients.
      Five patients are alive, with one disease free 7 years following resection of the
      thyroid metastasis. CONCLUSIONS: Thyroid metastases are clinically rare, with the
      kidney the most common primary site of origin. They usually occur when there are
      metastases elsewhere, sometimes many years after diagnosis of the original
      primary tumour. Surgical resection of an isolated metastasis may result in
      prolonged disease-free survival. Radiotherapy and chemotherapy may be of value in
      specific situations.

PMID- 15256230
TI  - Dystroglycan complex in cancer.
AB  - Abnormalities in the interactions between tumour cells, adhesion molecules and
      extracellular matrix proteins are often implicated in the behaviour of carcinoma
      cells. The alpha- and beta-dystroglycan (DG) proteins form part of the large
      dystrophin-associated protein (DAP) complex. They are involved in epithelial cell
      development, formation of the basement membrane and maintenance of tissue
      integrity. Specific changes and reduction or loss of DG expression have been
      reported in human breast, colon, head and neck, and prostate cancers, implicating
      it in tumour invasion and dissemination. Degradation of beta-DG by matrix
      metalloproteinase (MMP) enzymes may assist tumour dissemination. We report the
      present knowledge of the DG interactions in solid tumour biology.

PMID- 15256231
TI  - Candidate gene polymorphisms in solid cancers.
AB  - Accumulation of information from scientific advances in genetics and
      biotechnology has accelerated research investigating the inherent individual
      variation in disease susceptibility and severity. Gene polymorphisms, in
      particular single nucleotide polymorphisms, are being evaluated for their role in
      multi-factorial diseases such as cancer and inflammation. Most surgical diseases
      are multi-factorial and a better understanding and utilization of the information
      gained from such studies by clinicians/surgeons is likely to favorably influence
      patient outcome. In this article, we illustrate the types of genetic variation
      and the complexities involved in their study and discuss their potential in
      predicting both the occurrence and outcomes of solid cancers.

PMID- 15256232
TI  - A randomised study of axillary drainage and pectoral fascia preservation after
      mastectomy for breast cancer.
AB  - BACKGROUND: To reduce the risk of seroma after modified radical mastectomy in
      breast cancer patients, the use of suction axillary drainage is a standard
      procedure. The optimal time to remove the drain is not established. Whether the
      removal or preservation of the pectoral fascia influences the risk of seroma
      formation or loco-regional recurrence rate remains unclear. METHOD: The trial
      included 247 patients with breast cancer who underwent modified radical
      mastectomy in five Swedish hospitals 1993-1997. The median follow-up time was 6
      years. One hundred and twenty-two and 125 patients, respectively, were randomised
      between removal versus preservation of the pectoral fascia. Of these 247 patients
      a total of 198 patients were also randomised to have the drain removed 24 h
      postoperatively or to keep the drain in until discharge had decreased to less
      than 40 ml/24 h. RESULTS: Early removal of the axillary drain was associated with
      significantly more seromas and a shorter average postoperative hospital stay.
      There were no differences between the two groups regarding the rate of wound
      infections and/or hematoma formation. Removal or preservation of the pectoral
      fascia did not influence the formation of seroma or the amount of peroperative
      bleeding. A trend towards an increased risk for chest wall recurrence was
      observed in patients with preserved pectoral fascia (16/125 compared with 8/122;
      hazard ratio=2.0, 95% confidence interval=0.9-4.7). CONCLUSION: Early removal of
      axillary drain shortened the duration of hospital stay without any increase in
      wound complications. However, it yielded a significantly higher incidence of
      seroma. Seroma formation and the chest wall recurrence rate was not significantly
      influenced by the preservation of the pectoral fascia or not.

PMID- 15256233
TI  - Tumour location and axillary lymph node involvement in breast cancer: a series of
      3472 cases from Sweden.
AB  - AIM: This study investigates the potential relation between breast cancer
      location and axillary lymph node involvement (ALNI). METHODS: Out of all cases
      with unilateral first-time diagnosis of invasive breast cancer in Malmo, Sweden,
      between 1961 and 1991, 3472 underwent axillary dissection. The association
      between tumour location and ALNI was investigated using logistic regression
      analysis (adjusted for potential confounders) yielding odds ratios (OR), with a
      95% confidence interval. All analyses were repeated in different birth-year
      cohorts. RESULTS: Outer tumours (upper outer or lower outer quadrants), as
      compared to inner (upper inner and lower inner quadrants), were associated with a
      statistically significant risk of ALNI, OR: 1.31 (1.11-1.55). Central tumours
      were also associated with ALNI, OR: 2.61 (2.08-3.27). Among women born before
      1909, corresponding OR:s for outer tumours was 1.61 (1.19-2.18), and for central
      tumours 3.50 (2.32-5.28). CONCLUSIONS: Outer and central breast tumours are
      associated with a high risk of axillary lymph node involvement.

PMID- 15256234
TI  - Population-based sentinel lymph node biopsy in early invasive breast cancer.
AB  - INTRODUCTION: Sentinel lymph node biopsy (SLNB) has been proposed as a reliable
      method for staging of early invasive breast cancer (EIBC). In the present study
      we analyse the impact of this procedure when systematically applied to all
      unselected women of a community-based Breast Cancer Unit (BCU). METHODS: All
      consecutive women with unifocal cT1-2 (<or=3 cm) cN0 EIBC diagnosed at our BCU
      were considered for radiocolloid sentinel node localisation and biopsy. RESULTS:
      Only 387 of all consecutive 542 patients met eligibility criteria for SLNB.
      Reasons for ineligibility included tumour size, palpable axillary nodes,
      plurifocality and/or multicentricity, and refusal to undergo the procedure.
      Successful SLNB was performed in 362 patients (94% of those eligible), but in 108
      of these axillary dissection (AD) had to be performed anyway, mainly because of
      SLN-positivity. Therefore, SLNB ultimately allowed sparing axillary dissection in
      256 patients out of the entire population of women with EIBC. CONCLUSIONS:
      Radiocolloid-guided SLNB, when appropriately applied in the context of a
      population-based service, can help in sparing unnecessary AD, with its related
      costs and morbidity, in approximately half of all women presenting with EIBC. In
      absolute terms, in the EU this could result in approximately 100,000 unnecessary
      AD avoided each year.

PMID- 15256235
TI  - Immediate breast reconstruction does not lead to a delay in the delivery of
      adjuvant chemotherapy.
AB  - Immediate breast reconstruction (IBR) has been considered by some to lead to a
      delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether
      IBR led to a delay when compared to conservation surgery and non-reconstructive
      mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These
      were compared to 95 consecutively treated patients undergoing conservation
      surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR
      does not lead to a delay in the delivery of adjuvant chemotherapy when compared
      to standard non-reconstructive surgery and should not adversely affect breast
      cancer outcome.

PMID- 15256236
TI  - Anaemia prior to operation is related with poorer long-term survival in patients
      with operable rectal cancer.
AB  - PURPOSE: Local hypoxia has been linked to a higher risk of metastasis in patients
      with cancer of the uterine cervix and a haemoglobin concentration of 7.45 mmol/l
      or less. It is unknown whether the same holds true for rectal cancer. We
      evaluated the independent impact of pre-operative anaemia on survival in patients
      with rectal cancer. PATIENTS AND METHODS: A random set of 144 patients diagnosed
      with Dukes' A, B or C rectal cancer in the period 1995-1999 and registered in the
      database of the Eindhoven Cancer Registry was included in a survival analysis.
      Parameters tested were gender, age, pre-operative haemoglobin concentration,
      tumour stage and therapy. The ones that showed a relation with survival (log-rank
      test, p<0.1) were entered in a multivariate analysis. RESULTS: For patients
      without pre-operative anaemia, the hazard ratio of death was 0.35 (95% confidence
      interval 0.19-0.65, p=0.001), which indicates a three times higher mortality
      risk. For patients with a higher tumour stage (Dukes' B vs. Dukes' A or Dukes' C
      vs. Dukes' B) the hazard ratio of death was 1.52 (95% CI 1.04-2.23, p=0.03). For
      older patients (64-73 years vs. <64 years or >73 years vs. 64-73 years) the
      hazard ratio of death was 1.85 (95% CI 1.29-2.63, p=0.001). CONCLUSION: Long-term
      survival was significantly affected in rectal cancer patients with pre-operative
      anaemia. Further study on the relation between anaemia, tumour oxygenation and
      prognosis is needed, as it may have implications for future therapy.

PMID- 15256237
TI  - Successful sentinel node identification in colon carcinoma using Patent Blue V.
AB  - AIM: The aim of this study was to evaluate the use of Patent Blue V for
      identification of the sentinel node in patients with colon carcinoma. METHOD:
      From May 2002, 35 patients operated for colon carcinoma underwent lymphatic
      mapping using Patent Blue V as marker. Either directly after resection of the
      colon or during operation 2 ml of Patent Blue V was injected peritumourally, and
      the first 1 to 4 blue nodes were marked as sentinel nodes. Pathological
      evaluation was done on a single HE-stained section of all lymph nodes. Only if
      all sentinel nodes were negative for metastases, serial sectioning and additional
      immunohistochemical staining against keratine CK 7/8 was performed to reveal
      micrometastasis in the sentinel nodes. RESULTS: In 33/35 of patients at least one
      sentinel node was identified. In 10/33 the sentinel node was positive for
      metastases, and in 5/10 this was the only node containing metastases. One patient
      had a false negative sentinel node (accuracy 97%, sensitivity 91%). CONCLUSION:
      Using Patent Blue V, it is possible to identify the sentinel node in most
      patients with colon cancer. The results are comparable with other sentinel node
      studies using Lymphazurin.

PMID- 15256238
TI  - Long-term outcomes of radical surgery after gasless video endoscopic transanal
      excision of T1/T2 rectal cancers.
AB  - AIMS: We aim to clarify the long-term outcomes after an additional radical
      operation following gasless video endoscopic transanal rectal tumour excision
      (gasless VTEM) of 'high-risk' T1 and T2 rectal cancer. METHODS: Gasless VTEM
      involves modification of transanal endoscopic microsurgery (TEM) by incorporating
      a standard laparoscopic video camera without a CO(2) insufflation system. This
      study between 1993 and 2003 included six men and five women with a median age of
      64 years (range, 36-79). Specimens resected by gasless VTEM revealed (1) high
      risk T1 carcinomas with one of the following histological types: poorly
      differentiated, lymphovascular invasion, and massive invasion of the submucosa
      (submucosal invasion greater than 200-300 microm from the muscularis mucosa) and
      (2) T2 carcinomas. RESULTS: Eight patients had a high-risk T1 carcinoma and three
      patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a
      residual tumour was found in the specimen resected by the additional radical
      surgery. At a median follow-up of 86.5 months (range, 63.2-110.5), none of the
      patients developed tumour recurrence. Although one patient died with cancer at
      another organ site (hilar cholangiocarcinoma of the liver) 87 months after the
      additional radical surgery, the other 10 patients are alive and disease free.
      CONCLUSIONS: This study revealed favorable long-term outcomes after additional
      radical surgery following gasless VTEM in patients with high-risk T1 and T2
      carcinomas.

PMID- 15256239
TI  - Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the
      Dutch randomised FAMTX trial.
AB  - AIMS: Gastric cancer in Western countries is often diagnosed in an advanced stage
      and prognosis is poor. We performed a randomised trial with pre-operative FAMTX
      vs. surgery alone in order to evaluate the effect of pre-operative chemotherapy
      on resectability and survival. METHODS: Patients with proven adenocarcinoma of
      the stomach were randomised to receive four courses of chemotherapy using 5
      Fluorouracil, doxorubicin and methotrexate (FAMTX) prior to surgery or to undergo
      surgery alone. RESULTS: Fifty-nine patients were randomised; 29 patients were
      allocated to the FAMTX regimen prior to surgery and 30 patients had surgery
      alone. Resectability rates were equal for both groups. Complete or partial
      response was registered in 32% of the FAMTX group. With a median follow-up of 83
      months the median survival since randomisation is 18 months in the FAMTX group
      vs. 30 months in the surgery alone group (p=0.17). CONCLUSIONS: This trial could
      not show a beneficial effect of pre-operative FAMTX. Until large randomised
      studies prove otherwise, adequate surgery without delay is the best treatment for
      operable gastric cancer.

PMID- 15256240
TI  - A study of radiotherapy modalities combined with continuous 5-FU infusion for
      locally advanced gastrointestinal malignancies.
AB  - AIM: We describe the feasibility of combining infusional 5-fluorouracil (5-FU)
      with intraoperative radiation therapy (IORT). METHODS: Patients with surgically
      resectable locally advanced gastrointestinal cancers were treated concurrently
      during surgery with IORT and a 72 h infusion of 5-FU. Patients without previous
      external beam radiation therapy (EBRT) were subsequently treated with EBRT (40
      50Gy) concurrent with a 21-day continuous infusion of 5-FU. Pancreatic, gastric,
      duodenal, ampullary, recurrent colorectal, and recurrent anal cancer were
      included. RESULTS: During IORT/5-FU, no chemotherapy-related grade III or IV
      hematologic or gastrointestinal toxicity was noted. Post-surgical recovery or
      wound healing was not affected. One of nine patients who received post-operative
      radiation required a treatment break. During follow-up, there were more
      complications in patients with pelvic tumours, especially those with previous
      radiation. Nine patients have had local and/or local regional recurrences, two of
      these in the IORT field. CONCLUSIONS: Treatment with a combination of IORT and 5
      FU followed by EBRT and 5-FU is feasible. However, long-term complications may be
      increased in previously irradiated recurrent pelvic tumours.

PMID- 15256241
TI  - Limitation of diagnostic laparoscopy for patients with a periampullary carcinoma.
AB  - BACKGROUND: Diagnostic laparoscopy has been generally accepted in staging of
      patients with a periampullary malignancy. In our institution diagnostic
      laparoscopy was routinely used since 1992. However, in 1998 it was eliminated
      from the protocol since in a prospective study a yield of only 13% was found with
      a histologically proven accuracy of 60% for distant metastases. The effect of
      implementation of the new protocol on the occurrence of unnecessary laparotomies
      and the outcome after bypass surgery was assessed. METHODS: Between January 1999
      and December 2001, 186 consecutive patients with a potentially resectable
      periampullary carcinoma after radiological staging without diagnostic laparoscopy
      underwent explorative laparotomy with the intention to perform a curative
      pancreatoduodenectomy. Incidence of unresectability and outcome of palliative
      surgery were assessed. RESULTS: Resection could not be performed in 65 patients
      who underwent laparotomy because of metastatic disease (29 patients) and loco
      regional tumour ingrowth (34 patients). These patients underwent a bypass
      procedure with a median survival of 216 days. CONCLUSION: At laparotomy distant
      metastases were detected in 16% of the patients. Considering the fact that the
      detection rate of diagnostic laparoscopy is lower than 100%, the use of staging
      laparotomy is too limited to justify it as a routine procedure.

PMID- 15256242
TI  - Stop-flow technique for loco-regional delivery of high dose chemotherapy in the
      treatment of advanced pelvic cancers.
AB  - AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of
      high-doses of mitomycin C and anthacyclines in patients with inoperable,
      recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using
      percutaneous double-balloon arterial-venous catheters that selectively isolate
      the pelvic vascular section and a perfusion provided by an extracorporeal pump
      for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon
      rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm)
      plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts)
      infused into the isolated pelvic compartment. Blood samples were collected from
      the extracorporeal vascular flow and from peripheral plasma, and analysed for
      drug quantitation. RESULTS: During the procedure, there were no technical or
      hemodynamic complications, and no deaths occurred during surgery or in the
      postoperative period. MMC and DOXO peak levels measured in the extracorporeal
      system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3,
      MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the
      peripheral blood. Similarly; the area under concentration (AUC) versus time
      curves measured in the pelvic compartment during stop-flow perfusion were 19.9
      (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the
      corresponding value in peripheral circulation. The drug percentage eliminated in
      the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0
      24) were similar to those observed with iv bolus of equivalent drug doses.
      Minimal systemic and local toxicities were observed. One complete pathological
      and 2 partial responses were observed; pain remission in 8/10 patients. median
      survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into
      the local vasculature produces high pelvic-systemic concentration gradients
      during the stop-flow perfusion with limited local and systemic toxicity. The
      encouraging clinical results suggest further evaluation.

PMID- 15256243
TI  - Balloon catheter hypoxic abdominal perfusion with Mitomycin C and Melphalan for
      locally advanced pancreatic cancer: a phase I-II trial.
AB  - BACKGROUND: Developments in balloon catheter methodology have made hypoxic
      abdominal perfusion (HAP) with anti-tumour agents possible with only minimal
      invasive surgery. The initial reports on this modality and celiac axis stop-flow
      infusion for treatment of pancreatic cancer were very promising in terms of
      tumour response, median survival and pain reduction. Recent reports, however,
      have not been able to confirm these results and some have disputed the efficacy
      of these currently still applied treatment modalities. METHODS: Twenty-one
      patients with advanced pancreatic carcinoma were included in a phase I-II trial
      of HAP with MMC and Melphalan followed by celiac axis infusion (CAI) with the
      same agents six weeks later. Tumour response was assessed by abdominal-CT and by
      determining tumour markers. Effect on pain reduction was assessed by evaluation
      of pain registration forms. RESULTS: HAP resulted in augmented regional drug
      concentrations. One patient died after CAI due to acute mesenterial ischaemia.
      One agent-toxicity related death was observed in the phase-I study. Significant
      hematological toxicity was observed after HAP and CAI at MTD. No patients were
      considered resectable after treatment. Median survival after HAP was 6 months
      (range 1-29). Pain reduction was experienced by only 5/18 patients and was short
      lived. CONCLUSION: In contrast to earlier reports HAP and CAI with MMC and
      Melphalan did not demonstrate any benefit in terms of tumour response, median
      survival and pain reduction, compared to less invasive treatment options. As this
      treatment was associated with significant toxic side-effects and even one
      procedure related death, we do not consider this a therapeutic option in patients
      with advanced pancreatic cancer.

PMID- 15256244
TI  - Thyroglobulin monitoring after treatment of well-differentiated thyroid cancer.
AB  - AIMS: The prognosis for well-differentiated thyroid carcinomas is favourable
      after treatment, but the rate of recurrence is around 20%. Cervical
      ultrasonography, radio-iodine scans, and monitoring of serum thyroglobulin (Tg)
      levels allow these recurrences to be diagnosed. The management of patients with
      isolated elevated Tg levels is controversial in the presence of negative radio
      iodine scans. METHODS: The records of 57 patients diagnosed with recurrence of
      well-differentiated thyroid cancer were reviewed. Serum Tg was not evaluated in
      31 of these patients (group 1) and measured in the other 26 cases (group 2).
      RESULTS: Forty-three recurrence sites were found; four deposits in the thyroid
      bed and 39 cervical metastatic nodes, with an average of five nodes per patient.
      The radio-iodine scan was accurate in detecting 10/24 of cases, radiology in
      9/17, and elevated Tg levels in 20/25. Thirteen patients with recurrences
      diagnosed on the basis of Tg levels had negative radio-iodine scans. After
      surgery, Tg levels were normal in 10 patients from group 1 and 16 patients from
      group 2 (p=0.0078). CONCLUSIONS: Elevated Tg levels are indicative of disease
      progression or recurrence in patients who have previously been operated on for
      well-differentiated thyroid cancer. Even when the radiological study or radio
      iodine scan is normal, surgical re-exploration of the neck, with total
      thyroidectomy and lymphadenectomy, is advisable.

PMID- 15256245
TI  - Selective lymphadenectomy in sentinel node-positive patients may increase the
      risk of local/in-transit recurrence in malignant melanoma.
AB  - AIM: To determine whether sentinel lymph node biopsy (SLNB) for cutaneous
      malignant melanoma, particularly when followed by selective lymphadenectomy (SL)
      if involved nodes are found, alters the incidence of local/in-transit recurrence.
      METHODS: A literature overview of SLNB with or without SL has been performed,
      concentrating on the reported site(s) of first recurrence, and with specific
      reference to the incidence of local/in-transit recurrence. This is compared to
      the incidence after wide local excision (WLE) alone. RESULTS: The incidence of
      local/in-transit recurrence after WLE alone is 2.5-6.3% over a given range of
      tumour thickness, and is 9.0% after SLNB (with or without SL). In the latter
      group, the local/in-transit recurrence rate is 5.7% following SLNB alone in SN
      negative patients, and is 20.9% after SLNB plus SL in SN-positive patients.
      CONCLUSIONS: The incidence of local/in-transit recurrence following selective
      lymphadenectomy in sentinel node-positive patients may be greater than four times
      the incidence expected. This possible iatrogenic risk should be confirmed or
      refuted by randomised controlled trial. Until then the SLNB procedure should be
      regarded as experimental and not performed outside validation trials.

PMID- 15256246
TI  - Perivascular-submandibular lymph node metastasis in squamous cell carcinoma of
      the tongue and floor of mouth.
AB  - AIMS: The goal of this study was to investigate the incidence of occult
      metastasis in perivascular lymph node and nodal recurrence in these nodal pads in
      squamous cell carcinoma (SCC) of the tongue and floor of mouth. METHODS: We
      performed a prospective analysis of the incidence of an occult metastasis in the
      perivascular lymph nodes in 55 patients (41 with an oral tongue carcinoma and 14
      with a mouth floor carcinoma) who underwent an elective supraomohyoid neck
      dissection (SOHND) for SCC of the tongue and floor of mouth, from 1997 to 2002.
      99 SOHND procedures were performed as follows: 72 in tongue carcinomas and 27 in
      the mouth floor carcinomas. RESULT: Clinically occult, but pathologically
      positive perivascular lymph nodes occurred in four of 72 of the tongue carcinomas
      and two of 27 of the mouth floor carcinomas. The incidence of the regional
      recurrence at level I was three of 45. CONCLUSIONS: This preliminary report
      reveals a small incidence of perivascular lymph-node metastases and the
      infrequent nodal recurrence in this area after SOHND in early-staged tongue and
      floor of mouth SCC.

PMID- 15256247
TI  - Balloon catheter hypoxic abdominal and pelvic perfusion with tumour necrosis
      factor-alpha, Melphalan and Mitomycin C: a pharmacokinetic study in pigs.
AB  - BACKGROUND: Addition of tumour necrosis factor-alpha (TNF) to hypoxic abdominal
      perfusion (HAP) and hypoxic pelvic perfusion (HPP) with chemotherapeutic agents
      for treatment of un-resectable malignancies may lead to similar enhanced anti
      tumour effects as are observed when TNF is added to isolated limb perfusions
      (ILP) with Melphalan. Here, we validate the methodology of HAP and HPP using
      balloon catheter techniques, and investigate the distribution of TNF, Melphalan
      and Mitomycin C (MMC) over the regional and systemic blood compartments when
      applying these techniques. MATERIALS AND METHODS: Twelve pigs underwent HAP or
      HPP with TNF, Melphalan and MMC for 20 min. Throughout and after the procedures
      blood samples were obtained from hepatic, portal and systemic blood compartments
      and plasma concentrations of perfused agents were determined. RESULTS: We
      demonstrated that HAP and HPP result in temporary loco-regional concentration
      advantages of all perfused agents, although from start of perfusion significant
      systemic leakage occurred. CONCLUSION: On basis of these results it seems that
      the advantage in terms of regional plasma concentration of TNF may be
      insufficient for TNF-mediated effects to occur, making future addition of this
      cytokine to these procedures in the clinical setting questionable. The observed
      regional concentration advantages of MMC and Melphalan, however, warrant further
      studies on clinical application of these agents in both settings.

PMID- 15256248
TI  - Letter to the editor concerning 'intradermal radioisotope injection optimises
      sentinel lymph node identification in breast cancer'.

PMID- 15256250
TI  - Molecular cloning, genomic structure, and expression analysis of the mouse
      transcriptional intermediary factor 1 gamma gene.
AB  - Human transcriptional intermediary factor 1 gamma (Tif1gamma), also known as Ret
      fused gene 7 (RFG7), is a member of a novel family of transcriptional coregulator
      encoding genes which function in cell differentiation and development. Here, we
      report the structure and expression pattern of the mouse Tif1gamma gene. This
      gene comprises 20 coding exons spanning about 77 kb of genomic DNA on chromosome
      3F2, and encodes a 1142-amino-acid protein with 96% identity to the human
      protein. The locations of exon/intron boundaries correlated well with those for
      the regions of conserved amino acid sequences (RBCC motif, PHD finger and
      bromodomain). In situ hybridization analysis of the TIF1gamma mRNA on sections
      from staged mouse embryos revealed a low level of ubiquitous expression at
      midgestation, and higher expression levels within the brain and spinal cord
      epithelium at later developmental stages. Prominent expression was also found in
      developing sensory epithelia (cochlea, retina, olfactory epithelium), and in
      several developing organs including the thymus, lung, stomach, intestine, liver,
      and kidney cortex. In the adult mouse, Tif1gamma mRNA was detected by Northern
      blot analysis in all tissues examined, with the highest expression level in
      testis. In situ hybridization and immunohistochemistry studies revealed that
      expression of the Tif1gamma mRNA and protein varied according to the stage of the
      seminiferous epithelium cycle. Taken together, these results indicate-and serve
      as a basis for investigating-a possible involvement of Tif1gamma in the control
      of embryonic development and spermatogenesis.

PMID- 15256251
TI  - Mouse 3-phosphoglycerate dehydrogenase gene: genomic organization, chromosomal
      localization, and promoter analysis.
AB  - d-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is the first committed
      enzyme of l-serine biosynthesis in the phosphorylated pathway. We have recently
      demonstrated that, in developing and mature brain, expression of Phgdh is highly
      regulated in a cell lineage-specific manner, mainly in neuroepithelial stem
      cells, radial glia, and astrocytes (J. Neurosci. 21 (2001) 7691; Arch. Histol.
      Cytol. 66 (2003) 109). To gain insight into the regulatory mechanism of Phgdh
      expression, we have isolated a mouse genomic clone that contains the entire mouse
      Phgdh gene. Structural analysis demonstrated that the Phgdh gene spans
      approximately 27 kilobases (kb) in length and comprises 12 exons with 11
      intervening introns. Using fluorescent in situ hybridization (FISH), we mapped
      the gene to mouse chromosome 3, region F2-F3. Analysis of a 1.8 kb fragment of
      the 5'-flanking region showed that the classical TATA-box motif near
      transcription initiation sites was absent. Instead, a GC-rich proximal region
      containing a potential Sp1 recognition sequence was present; this region is
      conserved in mouse, rat, and human counterparts. Transient transfection analysis
      revealed that the cis-acting elements necessary for basal transcription of Phgdh
      are contained within the -196/+4 proximal sequence of the promoter, in which the
      conserved Sp1 recognition sites play an important role for basal promoter
      activity.

PMID- 15256252
TI  - Molecular cloning and characterization of the neonatal rat and mouse
      submandibular gland protein SMGC.
AB  - We report the molecular cloning and characterization of SMGC, a major secretory
      product and a marker of the type I (terminal tubule) cells of the neonatal rat
      and mouse submandibular gland. SMGC is expressed in the submandibular gland at
      high levels through postnatal day 20, but in the adult is present only in some
      intercalated duct cells. Rat and mouse SMGC have deduced molecular weights of
      67.8 and 74.4 kDa, respectively, are 37% Ser+Gly+Thr, and contain tandem repeats
      of between 8 and 60 amino acids. Secreted SMGC visualized by SDS-PAGE and silver
      staining is 89 kDa in rat and 105 kDa in mouse, although Western blot analyses
      with anti-SMGC antisera demonstrate multiple additional lower molecular weight
      forms. Contributions to the heterogeneity of SMGC include alternate splicing,
      proteolysis and N-glycosylation. Smgc is localized on rat chromosome 7q34-35 and
      on mouse chromosome 15E3, both immediately upstream of the high molecular weight
      salivary mucin, Muc19. Amino acid sequence identity between the signal peptides
      of SMGC, human MUC19 and pig submaxillary mucin suggest that rat and mouse Smgc
      and Muc19 arose from a single ancestral mucin gene.

PMID- 15256253
TI  - Isolation and characterization of five Fox (Forkhead) genes from the sponge
      Suberites domuncula.
AB  - Fox or Forkhead genes constitute a subgroup of the helix-turn-helix class of
      transcription factors with a characteristic and highly conserved DNA binding
      domain. To date, around 100 different Fox genes have been reported ranging from
      yeast to humans; these have been classified into 18 subclasses (A to P). Fox
      proteins are responsible for a wide range of functions and key roles in early
      developmental processes, during organogenesis and also for the function of the
      major organs and tissues in the adult. Here, we report the isolation and
      phylogenetic characterization of five members of the Fox family from the sponge
      Suberites domuncula. Four of them (Sd-FoxL2, Sd-FoxP, Sd-FoxD and Sd-FoxF) fall
      in the root of four of the already established families of vertebrates Fox,
      suggesting that in sponges, the basal group of metazoans, the main groups of Fox
      proteins were already established. We also demonstrate that they are
      differentially regulated during the culture of sponge cells.

PMID- 15256254
TI  - Molecular cloning and characterisation of the CD18 partner in ovine (Ovis aries)
      beta2-integrins.
AB  - The leukocyte integrins play a critical role in a number of cellular adhesive
      interactions during the immune response. We describe here the isolation and
      characterization of the ovine beta(2) (CD18) subunit, common to the leukocyte
      beta(2)-integrin family. The deduced 770-amino-acid sequence reveals a
      transmembrane protein with 81%, 83% and 95% identity with its murine, human and
      bovine homologues, respectively. Comparisons of CD18 sequences emphasize the
      functional importance of the beta(2) subunit I-like domain and included metal ion
      dependent adhesion site (MIDAS)-like motif and confirm that of the cytoplasmic
      tail. The data provided here will offer the possibility to explore new avenues in
      studies based on the ovine model.

PMID- 15256255
TI  - Phosphorylation of AfsR by multiple serine/threonine kinases in Streptomyces
      coelicolor A3(2).
AB  - AfsK, a protein serine/threonine kinase, autophosphorylates on serine and
      threonine residues and phosphorylates serine and threonine residues of AfsR, a
      transcriptional activator for afsS involved in secondary metabolism in
      Streptomyces coelicolor A3(2). pkaG encoding a 592-amino-acid protein and
      SCD10.09 (named afsL) encoding a 580-amino-acid protein, both of which encode an
      AfsK-like protein, were transcribed throughout growth. PkaG with a histidine-tag
      and the kinase catalytic domain of PkaG, produced in Escherichia coli,
      autophosphorylated dominantly on threonine and slightly on serine residues. In
      addition, these proteins phosphorylated AfsR on threonine and serine residues.
      The catalytic domain of AfsL also autophosphorylated and phosphorylated AfsR, on
      threonine and serine residues in both cases. AfsR was thus found to be
      phosphorylated by multiple kinases. Disruption of the chromosomal pkaG gene
      resulted in slightly reduced production of the pigmented antibiotic actinorhodin.
      These findings, together with the presence of about 40 AfsK homologues and at
      least five AfsR homologues in S. coelicolor A3(2), suggest that the regulatory
      networks via eukaryotic-type protein phosphorylation are more diverse and
      versatile than we have expected.

PMID- 15256256
TI  - Novel cis-element in intron 1 represses somite expression of zebrafish myf-5.
AB  - Myf-5 is a basic helix-loop-helix (bHLH) transcription factor that controls
      muscle differentiation. During early embryogenesis, myf-5 expression is
      transient, somite- and stage-specific. However, the negative regulation of myf-5
      is poorly understood. We constructed a plasmid [(-9977/-1)/E1/I1/E2/GFP] that
      contains the sequence -9977 to -1, exon 1 (E1), intron 1 (I1), and exon 2 (E2) of
      zebrafish (Danio rerio) myf-5 and a reporter GFP gene. This plasmid was
      microinjected into zebrafish zygotes. Surprisingly, the somite-specific
      expression rate of reporter GFP in the transgenic embryos was extremely low (2%,
      n=392), compared to that of (-9977/-1)/GFP (92%, n=210). Dramatic repression of
      myf-5 expression was also observed in embryos microinjected with plasmids in
      which the sequence -8600/-1, -2937/-1 or -290/-1 was linked to E1/I1/E2/GFP.
      Thus, intron 1 contains a silencer that specifically represses the activity of
      myf-5. Functional analysis of intron 1 showed a strong, negative, cis-regulatory
      element was located at +502/+835. Its function was orientation- and position
      dependent. The repressive capability of this silencer was completely dependent on
      two core motifs, IE1 (+502/+527) and IE2 (+816/+835), and a 156-bp spanning
      sequence that lies between them. This is the first study to identify a novel, cis
      acting silencer in intron 1 that is crucial to negatively regulating zebrafish
      myf-5 expression.

PMID- 15256257
TI  - Differential expression patterns of two new primary cell wall-related cellulose
      synthase cDNAs, PtrCesA6 and PtrCesA7 from aspen trees.
AB  - Based on elegant molecular genetic analyses, distinct classes of cellulose
      synthase (CesA) genes have been associated with either primary or secondary cell
      wall development in Arabidopsis. Here, we report on cloning of two new CesA
      cDNAs, PtrCesA6 and PtrCesA7 involved in the primary cell wall development in
      aspen (Populus tremuloides) trees. Both these distinct cDNAs, isolated from a
      developing xylem cDNA library, share only 60-67% identities with each other as
      well as with five other previously known aspen CesA cDNAs. Interestingly,
      PtrCESA6 from aspen, a dicot species, shares maximum identity of 81-84% with
      three CESA isoforms from maize and rice, two monocot species. On the other hand,
      PtrCESA7 shares a maximum identity of 86% with AtCESA2, a primary wall-related
      CesA member from Arabidopsis, a dicot species. Gene expression analyses by
      reverse transcriptase-polymerase chain reactions (RT-PCRs) suggested that both
      these genes are expressed at a low level in all aspen tissues examined but
      PtrCesA7 is expressed at a higher level than PtrCesA6. While corroborating these
      results, in situ mRNA hybridization studies using three different aspen organs
      also suggested that PtrCesA6 and PtrCesA7 genes are expressed in all expanding
      cells depositing primary cell wall but PtrCesA7 is expressed at a higher level
      than PtrCesA6. These differential gene expression profiles suggest that each of
      these CesAs may be playing a specific role during primary cell wall development
      in aspen trees. Isolation of two primary wall related CesA genes from xylem
      tissues also suggest their importance during xylem development, which is
      traditionally considered to be enriched in secondary cell wall forming cells of
      economical significance.

PMID- 15256258
TI  - Alternative usage of 5' exons in the chicken nerve growth factor gene: refined
      characterization of a weakly expressed gene.
AB  - Nerve growth factor (NGF) is the prototype member of the neurotrophin family.
      Identification of transcript structures and promoter regions is described here in
      view of clarifying the molecular basis of chicken NGF gene regulation. Chicken
      NGF complementary DNA (cDNA) was amplified from heart and brain mRNA using the
      single-strand ligation to cDNA (SLIC) procedure. Several cloning and sequencing
      rounds were necessary to elucidate the diversity of NGF transcripts. The chicken
      NGF gene was shown to possess, in addition to its unique 3' coding exon, five 5'
      exons grouped into two clusters that have been entirely sequenced. The first
      cluster encompasses three leader exons (1a, 1b and 1c) and is separated from the
      second cluster by a approximately 15 kilobases (kb) intronic sequence. "Exon
      walking" based on reverse transcription-polymerase chain reaction (RT-PCR)
      allowed to ascertain the length of the three leader exons. The second cluster
      contains exons 2 and 3, separated from each other by a approximately 2.4 kb
      intron, and lies approximately 0.5 kb upstream from coding exon 4. Combination of
      several mechanisms, such as differential usage of leader and internal exons,
      alternative transcription start inside exon 1b, second donor and acceptor sites
      in exon 1c and 4, respectively, leads to the production of at least 21 different
      transcripts. This remarkable diversity may represent a common feature largely
      underestimated for other weakly expressed genes. Preliminary RT-PCR expression
      study in a panel of chicken tissues shows that transcripts containing exon 1b are
      present in most tissues tested. Transcripts containing exon 1a are represented
      mainly in heart and reproductive organs, whereas transcripts containing exon 1c
      are mostly represented in peripheral organs other than heart. Complementary data
      are published as a Web supplement available at.

PMID- 15256259
TI  - Rearranged genomes of bovine blood cells can allow the development of clones till
      late fetal stages; but rare unrearranged genomes have greater potential and lead
      to adulthood.
AB  - Cloning via nuclear transfer is promising, but rather inefficient. Moreover, to
      date, relatively few data are available for a satisfactory phenotypic and
      genotypic characterization of the clones. Here, we analyze the genomes of clones
      derived from bovine peripheral blood mononucleated cells (PBMC), known to be
      composed mainly by lymphocytes. Their genomes are rearranged at either the
      immunoglobulin (Ig) or the T-cell-receptor (TCR) loci. The DNA of the single
      survivor and of four aborted fetuses were amplified by semi-quantitative PCR and
      sequenced. We found the expected rearrangements in DNA from lymphocytes, but
      neither in DNA from chondrocytes of the survivor, nor in DNA from brain cells of
      three of the aborted fetuses. This indicates that these four clones derived from
      somatic cells bearing unrearranged genomes and suggests that in a population of
      variably differentiated cells those harbouring unrearranged genomes are better
      donors. Brain cells of the fourth fetus present rearrangements at both loci. The
      sequences of these rearrangements differ from those obtained from PBMC because
      they appear unique, thus confirming the clonal origin of the fetus from a cell
      bearing a rearranged genome. To our knowledge, this is the first example in which
      both the placenta and the soma of a late fetus are coded for by the rearranged
      genome of a terminally differentiated cell, unambiguously identified through a
      specific genetic marker.

PMID- 15256260
TI  - The goat alphas1-casein gene: gene structure and promoter analysis.
AB  - The level of alphas1-casein in goat milk shows strong variations determined by at
      least 15 alleles associated with four different efficiencies of protein
      synthesis. The nucleotide sequence of the whole goat alphas1-casein-encoding gene
      (CSN1S1) plus 1973 nucleotides at the 5' flanking region and 610 nucleotides at
      the 3' flanking region was determined and aligned with its bovine counterpart.
      The gene is spread over 16.7 kb and consists of 19 exons varying in length from
      24 bp (exons 5, 6, 7, 8, 10, 13 and 16) to 385 bp (exon 19) and 18 introns from
      90 bp of intron 10 to 1685 bp of intron 2. Furthermore, highly conserved
      sequences, mainly located in the 5' flanking region, were found between this gene
      and other casein-encoding genes. Finally, seven interspersed repeated elements
      (10 in the bovine CSN1S1 gene) were also identified at four different locations
      of the sequenced region: 5' untranscribed region and introns 2, 8 and 11.

PMID- 15256261
TI  - Alternatively spliced isoforms of a novel stromal RNA regulating factor.
AB  - Bone marrow stromal cells (MSC) are pluripotent cells that possess a unique
      capacity to differentiate under appropriate conditions into various lineages. The
      MSC differentiation is dependent on factors that can switch on and maintain a
      relevant genetic program to make a particular cell type. The present study
      describes the cloning and molecular analysis of a novel gene, SRRF (Stromal RNA
      Regulating Factor), suggested to be involved in RNA processing in MSC. We cloned
      two alternatively spliced isoforms of this gene, transcripts A and B, from the
      marrow stromal cells expression library. Differential expression analysis
      demonstrated a restricted expression of the transcripts to MSC, while other
      spliced forms of this gene were detected in other tissues. The bioinformatic
      analysis of the two isoforms revealed RNA binding motifs (RRM), protein-protein
      and protein-DNA interaction motifs. Participation of SRRF isoforms in post
      transcriptional events in MSC is believed to govern the tissue specificity of RNA
      transcription and to have an important role in regulation of the RNA expression
      that directs the MSC differentiation pathway.

PMID- 15256262
TI  - Identification of a conserved cluster of skin-specific genes encoding secreted
      proteins.
AB  - Terminal differentiation of keratinocytes results in the formation of a cornified
      layer composed of cross-linked intracellular and extracellular material. Using a
      signal trap expression screening strategy, we have identified four cDNAs encoding
      secreted proteins potentially involved in this process. One of the cDNAs is
      identical to the short isoform of suprabasin, a recently described epidermis
      specific protein, which is shown here to contain a functional secretory signal.
      The second cDNA, sk89, encodes a protein of 493 amino acids, rich in glycine and
      serine residues. The third cDNA encodes a C-terminal fragment of SK89 (amino
      acids 410-493). It comprises exons 13 to 18 of the sk89 locus but transcription
      starts at an isoform-specific exon encoding a distinct secretory signal. The
      fourth cDNA encodes keratinocyte differentiation-associated protein (KDAP), a
      precursor protein of 102 amino acids. Subcellular localization by
      immunofluorescence and detection of the tagged proteins by Western blotting
      confirmed that the four proteins are secreted. Northern analysis and in situ
      hybridization revealed that expression of the corresponding genes was restricted
      to the suprabasal keratinocytes of the epidermis. These genes encoding epidermis
      specific secreted products are found in a conserved cluster on human chromosome
      19q13.12 and on mouse chromosome 7A3.

PMID- 15256263
TI  - Ependymin, a gene involved in regeneration and neuroplasticity in vertebrates, is
      overexpressed during regeneration in the echinoderm Holothuria glaberrima.
AB  - We report the characterization of an ependymin-related gene (EpenHg) from a
      regenerating intestine cDNA library of the sea cucumber Holothuria glaberrima.
      This finding is remarkable because no ependymin sequence has ever been reported
      from invertebrates. Database comparisons of the conceptual translation of the
      EpenHg gene reveal 63% similarity (47% identity) with mammalian ependymin-related
      proteins (MERPs) and close relationship with the frog and piscine ependymins. We
      also report the partial sequences of ependymin representatives from another
      species of sea cucumber and from a sea urchin species. Conventional and real-time
      reverse transcriptase polymerase chain reaction (RT-PCRs) show that the gene is
      expressed in several echinoderm tissues, including esophagus, mesenteries,
      gonads, respiratory trees, hemal system, tentacles and body wall. Moreover, the
      ependymin product in the intestine is overexpressed during sea cucumber
      intestinal regeneration. The discovery of ependymins in echinoderms, a group well
      known for their regenerative capacities, can give us an insight on the evolution
      and roles of ependymin molecules.

PMID- 15256264
TI  - Isolation and characterization of a single-copy actin gene from a sterile mutant
      of Ulva pertusa (Ulvales, Chlorophyta).
AB  - We constructed a cDNA library from sterile Ulva pertusa (Ulvales, Chlorophyta),
      and isolated and characterized a full-length cDNA clone encoding actin. The actin
      (ACT) cDNA consisted of 1487 nucleotides (nt) and had an open reading frame (ORF)
      encoding a polypeptide of 377 amino acid (AA) residues. The ACT gene had one
      intron in the 5'-untranslated region and three introns in the coding region.
      Transcription started 26 nt downstream of the putative TATA box. A potential
      polyadenylation signal, TGTAG, was located 100 nt downstream of the terminator
      codon, TAG. Amino acid alignment with actins from various algae and land plants
      showed that sterile U. pertusa actin was more similar to actins from Chlorophyta,
      Phaeophyta, Euglenophyta, and higher plants (over 76.9%) than to actins from
      Rhodophyta. Southern blot analysis indicated that the sterile U. pertusa genome
      has only a single actin-encoding gene. Thalli grown on a 12D/12L photoperiod
      increased in surface area some two-fold over 24 h regardless of the nutritional
      conditions. The growth rate of thalli during the light period was significantly
      higher than that during the dark period. Northern hybridization indicated that
      the expression of actin mRNA was induced and repressed by the light and dark
      treatments, respectively. These results suggest that the U. pertusa cell division
      cycle has a periodicity of 24 h and that the ACT gene is highly transcribed
      during cell growth and development in the light period.

PMID- 15256265
TI  - A vitellogenin chain containing a superoxide dismutase-like domain is the major
      component of yolk proteins in cladoceran crustacean Daphnia magna.
AB  - A cDNA encoding vitellogenin (VTG), a precursor of a major yolk protein, vitellin
      (VTN), was isolated from cladoceran crustacean Daphnia magna. The deduced amino
      acid sequence of DmagVTG1, the polypeptide encoded by the cDNA, contained a
      possible signal peptide sequence of 16 amino acid (aa) residues. The possible
      mature form of DmagVTG1 consists of 1985 aa residues with a calculated molecular
      mass of 223,070 Da. The large lipid transfer (LLT) module and a part of the von
      Willebrand factor D (VWD) module found in the aa sequences of VTGs of many other
      organisms are well conserved in DmagVTG1. Phylogenetic analysis suggested that
      the LLT module of DmagVTG1 is more closely related to those of insect VTGs than
      those of decapodan crustaceans. A unique feature of DmagVTG1 is that it has a
      superoxide dismutase (SOD)-like domain at its NH(2)-terminus. Antisera against
      the SOD-like domain, the NH(2)-terminal part of the VTG domain and the COOH
      terminal part of the VTG domain, respectively, were prepared and used for
      analysis of D. magna yolk proteins. Six species (I to VI) of major protein
      complexes were found in D. magna parthenogenetic eggs isolated immediately after
      ovulation. Complexes IV and V were the most abundant. DmagVTG1 was a component of
      Complexes III, IV and V, and the most abundant polypeptide in D. magna eggs. The
      protein complexes underwent gradual proteolysis during development. One of the
      primary sites of cleavage was between the two successive Arg residues located at
      the 1454th and 1455th positions of DmagVTG1.

PMID- 15256266
TI  - Alternative splicing produces transcripts coding for alpha and beta chains of a
      hetero-dimeric phosphagen kinase.
AB  - Glycocyamine kinase (GK) catalyzes the reversible phosphorylation of glycocyamine
      (guanidinoacetate), a reaction central to cellular energy homeostasis in certain
      animals. GK is a member of the phosphagen kinase enzyme family and appears to
      have evolved from creatine kinase (CK) early in the evolution of multi-cellular
      animals. Prior work has shown that GK from the polychaete Neanthes (Nereis)
      diversicolor exits as a hetero-dimer in vivo and that the two polypeptide chains
      (termed alpha and beta) are coded for by unique transcripts. In the present
      study, we demonstrate that the GK from a congener Nereis virens is also hetero
      dimeric and is coded for by alpha and beta transcripts, which are virtually
      identical to the corresponding forms in N. diversicolor. The GK gene from N.
      diversicolor was amplified by PCR. Sequencing of the PCR products showed that the
      alpha and beta chains are the result of alternative splicing of the GK primary
      mRNA transcript. These results also strongly suggest that this gene underwent an
      early tandem exon duplication event. Full-length cDNAs for N. virens GKalpha and
      GKbeta were individually ligated into expression vectors and the resulting
      constructs used to transform Escherichia coli expression hosts. Regardless of
      expression conditions, minimal GK activity was observed in both GKalpha and
      GKbeta constructs. Inclusion bodies for both were harvested, unfolded in urea and
      alpha chains, beta chains and mixtures of alpha and beta chains were refolded by
      sequential dialysis. Only modest amounts of GK activity were observed when alpha
      and beta were refolded individually. In contrast, when refolded the alpha and
      beta mixture yielded highly active hetero-dimers, as validated by size exclusion
      chromatography, electrophoresis and mass spectrometry, with a specific activity
      comparable to that of natural GK. The above evidence suggests that there is a
      preference for hetero-dimer formation in the GKs from these two polychaetes. The
      evolution of the alternate splicing and an additional exon in these GKs,
      producing alpha and beta transcripts, can be viewed as a possible compensation
      for a mutation(s) in the original gene, which most likely coded for a homo
      dimeric protein.

PMID- 15256267
TI  - Regulation of expression of the receptors controlling gastric acidity.
AB  - Gastric acid secretion is regulated by the stimulatory effects of gastrin,
      histamine and acetylcholine and the inhibitory actions of somatostatin on their
      respective receptors. We proposed that the expression of these receptors could be
      regulated at the transcription level by agonists and antagonists known to effect
      acid secretion. A quantitative "real-time" PCR method was used to determine
      changes in mRNA expression for these receptors. The agonists, pentagastrin and
      histamine, and the H2 antagonist, ranitidine, were infused over a 6 h period to
      conscious sheep. Blood, antral and fundic tissue samples were taken for analysis.
      Both pentagastrin and histamine resulted in elevated plasma somatostatin
      concentrations during the treatment. Ranitidine stimulated a fourfold increase in
      plasma gastrin while histamine caused a transient decrease. Except for an
      increase in antral gastrin following ranitidine infusion, there was no
      significant change in gastric gastrin and somatostatin concentration. Histamine
      (H2) receptor mRNA expression in the antrum was significantly increased by
      pentagastrin and decreased by ranitidine. Pentagastrin also stimulated a
      significant increase in the level of muscarinic (M3) receptor mRNA in the antrum.
      Antral somatostatin II receptor mRNA was significantly decreased by histamine. In
      the fundus, pentagastrin infusion resulted in a significant increase in histamine
      receptor mRNA and a decrease in the muscarinic receptor mRNA. This work
      demonstrates that the receptors involved in the regulation of acid secretion can
      be regulated by local events.

PMID- 15256268
TI  - The relaxant effect of urocortin in rat pulmonary arteries.
AB  - Urocortin is a potent vasodilator, which plays physiological or
      pathophysiological roles in systemic circulation. However, little is known about
      its action on pulmonary circulation. The present study was aimed to characterize
      some cellular mechanisms underlying the relaxant effect of urocortin in isolated
      rat pulmonary arteries. Changes in isometric tension were measured on small
      vessel myographs. Urocortin inhibited U46619-induced contraction with reduction
      of the maximal response. Urocortin-induced relaxation was independent of the
      presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG
      nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did
      not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing
      factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor
      reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in
      30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2
      induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but
      not other K+ channel blockers reduced the relaxant responses to urocortin.
      Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in
      normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our
      results show that urocortin relaxed rat pulmonary arteries via CRF receptor
      mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel
      independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute
      to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries
      partly via inhibition of a PKC-dependent contractile mechanism.

PMID- 15256269
TI  - Cellular models for the analysis of signaling by protein kinase B and the
      forkhead transcription factor FKHR (Foxo1a).
AB  - The transcription factor FKHR (FOXO1a) is regulated by protein kinase B (PKB) and
      insulin controls the expression of hepatic genes like glucose-6-phosphatase
      (G6Pase) at least in part via these proteins. However, insulin is known to
      activate several pathways and it is therefore difficult to establish which
      effects of the hormone are attributed to PKB and FKHR signaling. The aim of the
      present study was the generation of cellular models which allow the specific
      analysis of molecular events controlled by PKB and FKHR, respectively. We
      generated two H4IIEC3 rat hepatoma cell lines stably expressing either a
      hydroxytamoxifen-regulatable form of PKB (myristoylated PKB estrogen receptor
      chimera; MER-PKB) or FKHR (FKHR estrogen receptor chimera; FKHR-ER) by retroviral
      infection and determined the regulation of the G6Pase transcript by Northern
      blotting and enzyme assays. Activation of the regulatable PKB fusion protein
      almost completely reduced the dexamethasone/cAMP-stimulated G6Pase mRNA levels
      comparable to the effect of insulin. In contrast, stimulation of FKHR-ER with
      tamoxifen increased the expression of the dexamethasone/cAMP-induced G6Pase mRNA
      and the G6Pase enzymatic activity about 2.5- to 3-fold. The present data
      demonstrate that activation of PKB is sufficient to mimic the effect of insulin
      on the expression of G6Pase and that FKHR acts as an activator of the G6Pase gene
      indicating that the established cellular models are suitable for the specific
      analysis of downstream targets of these signaling molecules. Therefore, these
      cell systems might serve as useful tools for the development of anti-diabetic
      drugs.

PMID- 15256270
TI  - Ghrelin stimulates motility in the small intestine of rats through intrinsic
      cholinergic neurons.
AB  - BACKGROUND AND PURPOSE: Ghrelin is a peptide discovered in endocrine cells of the
      stomach. Since ghrelin mRNA expression and plasma levels are elevated in the
      fasting state, we investigated the effects of ghrelin on the interdigestive
      migrating myoelectric complex (MMC) in the small intestine in vivo and compared
      with motor effects of ghrelin in vitro. METHODS: Sprague-Dawley rats were
      supplied with a venous catheter and bipolar electrodes in the duodenum and
      jejunum for electromyography of small intestine in awake rats. In organ baths,
      isometric contractions of segments of rat jejunum were studied. RESULTS: Ghrelin
      dose-dependently shortened the MMC cycle length at all three recording points. At
      the duodenal site, the interval shortened from 17.2+/-2.0 to 9.9+/-0.8 min during
      infusion of ghrelin (1000 pmol kg(-1) min(-1)) and at the jejunal site from
      17.5+/-2.2 to 10.5+/-0.8 min. Ghrelin contracted the muscle strips with a pD2 of
      7.97+/-0.47. Atropine (10(-6) M) in vitro and (1 mg kg(-1)) in vivo blocked the
      effect of ghrelin. CONCLUSION: Ghrelin stimulates interdigestive motility through
      cholinergic neurons. Ghrelin also stimulates motility, in vitro, suggesting that
      ghrelin receptors are present in the intestinal neuromuscular tissue and mediate
      its effects via cholinergic mechanisms.

PMID- 15256271
TI  - A role for chromogranin A (4-16), a vasostatin-derived peptide, on human colonic
      motility. An in vitro study.
AB  - The hypothesis that CgA-derived peptides may be involved in mechanisms modulating
      motility was tested. Human colonic smooth muscles were studied using an organ
      bath technique. Acetic acid (AA) effects were characterized on spontaneous
      mechanical activities (SMA) and on responses to transmural nerve stimulation
      (NS). AA induced a significant decrease in tone and abolished SMA; this effect
      was insensitive to either TTX or L-NAME/apamin. The AA-induced inhibitory effects
      were significantly reduced in the presence of CgA4-16. This effect was
      insensitive to TTX or L-NAME/apamin. Furthermore, AA-induced effects were blocked
      in the presence of BAYK8644 and CgA4-16 together. The inhibitory effect of
      nifedipine was delayed in the presence of CgA4-16. NS induced a triphasic
      response. Only the excitatory components were reduced in the presence of AA. This
      effect was dose-related and remained unchanged in the presence of CgA4-16 alone,
      but was blocked in the presence of simultaneous administration of CgA4-16 and L
      NAME/apamin. AA application induced inhibition of human colon motility in vitro.
      This effect may be mediated through an action on L-type calcium channels. CgA4-16
      may display a protective role, which prevents the inhibition of motility due to
      AA to occur, by acting on both smooth muscle and afferent terminals.

PMID- 15256272
TI  - Arg-vasopressin increases proliferation of human osteoblast-like cells and
      decreases production of interleukin-6 and macrophage colony-stimulating factor.
AB  - Patients with arginine-vasopressin (AVP) deficiency have been reported to have a
      decreased bone mass. The mechanism behind this is not known. In this study, the
      effects of AVP on primary human osteoblast-like (hOB) cells and SaOS-2 cells were
      investigated. Cell proliferation was measured by [3H]thymidine incorporation or a
      commercially available kit (EZ4U), and protein synthesis by [3H]proline
      incorporation. In addition, the production of interleukin-6 (IL-6) and macrophage
      colony-stimulating factor (M-CSF) in hOB cells was determined. AVP at 10-100
      pmol/l increased cell proliferation in hOB and SaOS-2 cells (p < 0.05). Protein
      synthesis increased in SaOS-2 cells incubated with 10-100 pmol/l AVP (p < 0.01).
      When hOB and SaOS-2 cells were incubated with AVP together with a vasopressin
      receptor-1 (V1)-antagonist ([beta-Mercapto-beta,beta-cyclopenta
      methylenepropionyl1,O-Me-Tyr2,Arg8]-vasopressin) or a protein kinase C (PKC)
      inhibitor (chelerythrine) the increase in cell proliferation in response to AVP
      was abolished. The production of IL-6 and M-CSF was decreased in hOB-cells
      incubated with 10 pmol/l AVP (p < 0.01). In addition, by RT-PCR, we found
      evidence for expression of mRNA for the vasopressin 1a (V1a)-receptor in hOB
      cells. In conclusion, AVP stimulated proliferation of hOB- and SaOS-2 cells. We
      suggest that the effect was mediated through the V1-receptor. Additionally, AVP
      decreased production of IL-6 and M-CSF from the hOB cells. Moreover, the V1a
      receptor seems to be expressed in hOB cells.

PMID- 15256273
TI  - Effects of adrenomedullin on cell proliferation in rat adventitia induced by
      lysophosphatidic acid.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipid having growth factor-like
      activity on fibroblasts and is involved in cardiovascular diseases such as
      hypertension and heart failure by inducing vascular remodeling, characterized by
      fibroblast proliferation and migration in adventitia. Among various bioactive
      factors that LPA works with, adrenomedullin (ADM) is a multiple functional
      peptide with an important cytoprotective effect against cardiovascular damage. We
      studied rat aortic adventitia to explore the possible paracrine/autocrine
      interaction between endogenous ADM and LPA. LPA stimulation of the adventitia to
      secrete ADM and express its mRNA was concentration dependent. ADM inhibited LPA
      induced proliferation in adventitial cells and attenuated the activity of mitogen
      activated protein kinase (MAPK) stimulated by LPA. In contrast, treatment with
      specific antagonists of the ADM receptor potentiated the LPA-induced
      proliferation in adventitial cells. We concluded that LPA stimulates the
      adventitia to produce and secrete ADM, which in turn regulates the vascular
      biological effects of LPA.

PMID- 15256274
TI  - Effect of central thyrotropin-releasing hormone on pancreatic blood flow in rats.
AB  - Central neuropeptides play a role in physiological regulation through the
      autonomic nervous system. Thyrotropin-releasing hormone (TRH) is a neuropeptide
      distributed throughout the central nervous system and acts as a neurotransmitter
      to regulate gastric and hepatic functions through vagal-cholinergic pathways. In
      this study, the central effect of TRH on pancreatic blood flow was investigated
      in urethane-anesthetized rats. Pancreatic blood flow was determined by laser
      Doppler flowmetery. After measurement of basal blood flow, a stable TRH analog,
      RX 77368 (1-50 ng) or saline was injected intracisternally. Pancreatic blood flow
      was observed for 120 min thereafter. In some experiments, pretreatment with
      atropine methyl nitrate (0.15 mg/kg, i.p.), NG-nitro-L-arginine-methyl ester (10
      mg/kg, i.v.), or 6-hydroxydopamine (6-OHDA;180 mg/kg, i.p.), or subdiaphragmatic
      vagotomy was performed. Intracisternal injection of TRH analog dose-dependently
      increased pancreatic blood flow with a peak response occurring 30 min after
      injection. The stimulatory effect of TRH analog on pancreatic blood flow was
      blocked by vagotomy, atropine, and NG-nitro-L-arginine-methyl ester, but not by 6
      hydroxydopamine. Intravenous administration of the TRH analog did not influence
      pancreatic blood flow in the same animal model. These results indicate that TRH
      acts in the central nervous system to stimulate pancreatic blood flow through
      vagal-cholinergic and nitric oxide-dependent pathways.

PMID- 15256275
TI  - The smooth muscle pharmacology of maximakinin, a receptor-selective, bradykinin
      related nonadecapeptide from the venom of the Chinese toad, Bombina maxima.
AB  - Structural homologues of vertebrate regulatory peptides found in defensive skin
      secretions of anuran amphibians often display enhanced bioactivity and receptor
      binding when compared with endogenous mammalian peptide ligands. Maximakinin, a
      novel N-terminally extended bradykinin (DLPKINRKGPRPPGFSPFR) from the skin venom
      of a Chinese toad (Bombina maxima), displays such activity enhancement when
      compared with bradykinin but is additionally highly selective for mammalian
      arterial smooth muscle bradykinin receptors displaying a 50-fold increase in
      molar potency in this smooth muscle type. In contrast, a 100-fold decrease in
      molar potency was observed at bradykinin receptors in intestinal and uterine
      smooth muscle preparations. Maximakinin has thus evolved as a "smart" defensive
      weapon in the toad with receptor/tissue selective targeting. Natural selection of
      amphibian skin venom peptides for antipredator defence, through inter-species
      delivery by an exogenous secretory mode, produces subtle structural stabilisation
      modifications that can potentially provide new insights for the design of
      selectively targeted peptide therapeutics.

PMID- 15256276
TI  - The rat pancreatic islets: a reliable tool to study islet responses to
      cholecystokinin receptor occupation.
AB  - This study was undertaken to show that rat purified islets can be used as a
      reliable tool to study some aspects of human islet's physiology related to CCKR
      occupation. Therefore, isolated foetal, adult human and rat islets were compared
      for (1) CCKR subtypes mRNA and protein expression and somatostatin (SS) mRNA and
      (2) co-localization of these receptors with insulin, glucagon and SS. Finally,
      rat islets were tested for their responsiveness to stimulation. Purified human
      and rat islets were used for CCKR subtypes and SS mRNA estimation by RT-PCR and
      protein by Western blots. Receptors and hormones co-localizations were evaluated
      by confocal microscopy. Hormones secretion served to determine rat islets
      responsiveness. Islets of both species express CCKA and CCKBR mRNA and proteins
      and SS mRNA. The CCKAR co-localizes with insulin and glucagon and the CCKBR with
      SS. Insulin release was increased 5-fold in response to 16 mM glucose and SS
      secretion reached 1.3- and 1.7-fold increments above basal in response to
      forskolin and IBMX. In conclusions, human and rat islets have comparable CCKR
      subtypes localized on the same cells; they also express SS mRNA. The rat islets
      are functional as they secrete but their response to hormonal stimulation remains
      to be clarified. These rat islets can thus serve as tools to study islets
      physiology.

PMID- 15256277
TI  - Angiotensin converting enzyme and the arrhythmogenic action of angiotensin I:
      cardiac cell membrane as a site of angiotensin I conversion.
AB  - The influence of angiotensin I (Ang I) on heart excitability and refractoriness
      was investigated in isolated right ventricular muscle of adult rats as well as in
      isolated ventricular myocytes. The results indicated that Ang I (10(-8) M) added
      to the bath solution, decreased the action potential duration from 50.4 +/- 3.6
      to 33.9 +/- 3.9 ms (P < 0.05) and reduced significantly the cardiac
      refractoriness. Consequently, a discharge of spontaneous action potentials was
      elicited when a second stimulus was applied during the relative refractory
      period. Moreover, the conduction velocity was reduced from 56.9 +/- 2.9 to 40 +/-
      3.2 cm/s (P < 0.05). The question whether the effect of Ang I was related to its
      conversion to Ang II, was investigated on tissues exposed to enalapril maleate
      (10(-8) M). Under these conditions, the effect of Ang I was totally suppressed.
      Similar results were found with losartan (10(-7) M). To investigate if the
      conversion of Ang I to Ang II occurs at the level of surface cell membrane,
      measurements of inward calcium current (ICa) were performed in myocytes isolated
      from the rat ventricle. ICa was measured before and after the administration of
      Ang I (10(-8) M). The results indicated that Ang I (10(-8) M), added to the bath
      solution, reduced the peak ICa density by 26.3 +/- 2.6% (P < 0.05), an effect
      abolished by enalapril maleate (10(-8)M). CONCLUSION: Evidence is presented for
      the first time, that Ang I is converted to Ang II at the surface cell membrane in
      cardiac muscle with consequent generation of cardiac arrhythmias which are
      elicited by Ang II.

PMID- 15256278
TI  - Molecular cloning and functional expression of the mouse CRF2(a) receptor splice
      variant.
AB  - The mouse corticotropin-releasing factor (CRF) type 2a receptor (CRF2(a)) splice
      variant was cloned by a PCR-based approach. The corresponding cDNA was found to
      encode a 411-amino acid polypeptide with highest sequence homology to the rat
      CRF2(a) receptor. By semiquantitative reverse transcriptase PCR (RT-PCR)
      analysis, the CRF2(b) mRNA was mainly found in the heart and skeletal muscle with
      only low level expression in the brain. In contrast, CRF2(a) mRNA was restricted
      to the brain with major expression sites in the cortex, hippocampus, hypothalamus
      and telencephalon. Binding and cyclic AMP stimulation studies showed a similar
      ligand selective profile for both mCRF2 receptor splice variants. A notable
      exception however, was urotensin I which displayed a approximately 3-fold higher
      affinity for the CRF2(a) receptor and also stimulated cyclic AMP production in
      mCRF2(a)-transfected cells with a approximately 3-fold higher potency than in
      mCRF2(b)-transfected cells. These data show that the mouse like other mammalian
      species expresses two ligand-selective CRF2 receptor splice variants and that the
      mCRF2(a) receptor is the predominant central CRF2 receptor in the mouse.

PMID- 15256279
TI  - Effects of cholecystokinin and bombesin on the expression of preprosomatostatin
      encoding genes in goldfish forebrain.
AB  - It was previously demonstrated that both cholecystokinin (CCK) and bombesin (BBS)
      stimulate growth hormone (GH) secretion in goldfish. Both peptides induce satiety
      and it was speculated that they integrate satiation and the postprandial increase
      in GH circulating levels. In the present paper we investigated the effects of CCK
      and BBS on the forebrain expression of the somatostatin gene family in goldfish
      to analyze if somatostatin peptides may be part of the effector mechanisms of CCK
      and BBS. We found that peripherally as well as centrally administered CCK
      decreases mRNA levels of preprosomatostatin (PSS)-I that encodes for SRIF-14,
      having no effects on PSS-II and PSS-III, which encode for gSRIF-28 and [Pro2]
      SRIF-14, respectively. In addition, a direct action on the pituitary to stimulate
      GH release, this inhibition of PSS-I expression provides a possible mechanism for
      CCK to increase postprandial GH levels. On the other hand, BBS inhibits the
      forebrain expression of PSS-I and PSS-II but does not affect PSS-III regardless
      of the route of administration. We conclude that this could be the most likely
      mechanism of action of BBS to increase GH secretion, since there are few BBS
      immunoreactive (IR) fibers and BBS binding sites in the anterior pituitary of
      goldfish.

PMID- 15256280
TI  - GIP1-39, a novel insulinotropic peptide form and aspects on its mechanism of
      action.
AB  - GIP1-39, a novel chain-length form of GIP (gastric inhibitory polypeptide or
      glucose-dependent insulinotropic polypeptide), has been purified recently from
      porcine intestine and found to exist abundantly in this tissue. We have
      characterized that GIP1-39 is an insulinotropic peptide, and demonstrated that
      GIP1-39 is more potent in stimulating insulin secretion from rat pancreatic
      islets than GIP1-42, the insulinotropic polypeptide reported originally.
      Therefore, we have further investigated some aspects on the mechanism behind the
      insulinotropic effect of GIP1-39 in single rat pancreatic beta cells. GIP1-39 at
      100 nM was able to significantly increase intracellular Ca2+ concentration
      ([Ca2+]i), and capable of enhancing exocytosis assessed by membrane capacitance
      measurement. The novel GIP1-39 might be a more optimal molecular pattern in
      stimulating insulin secretion and deserves to be further investigated
      biologically and clinically.

PMID- 15256281
TI  - Enriched protein diet-modified ghrelin expression and secretion in rats.
AB  - Gastrointestinal (GI) integrity and function are regulated by nutrition and
      growth factors. The discovery of ghrelin, a natural growth hormone (GH)
      secretagogue produced by the gastrointestinal (GI) tract, is a potential link
      between diet and growth signals. The aim of this study was to evaluate
      macronutrient effect on ghrelin expression and secretion in addition to some
      possible function in intestinal trophic status. Wistar rats were fed a high
      carbohydrate, high-protein (HP), high-fat or standard (St) diet. Animals received
      the same daily food volume and caloric intake. After 7 days, animals were fasted
      for 24 h and blood and tissue samples were obtained just before feeding or at 2
      or 6 h after feeding. Fasting high-protein-fed rats had higher ghrelin plasma
      levels than with rats fed the high-carbohydrate, high-fat or standard diets. Two
      hours after refeeding, ghrelin plasma levels had decreased in all groups with a
      slight recovery at 6 h after refeeding, except in the high-protein group. Ghrelin
      plasma levels in rats fed with the high-protein diet correlated negatively with
      their GH and insulin-like growth factor 1 (IGF-1) plasma concentrations which
      were also the lowest among the study groups. In conclusion, ghrelin secretion was
      nutritionally manipulated because a protein-enriched diet increased its levels.

PMID- 15256282
TI  - Charge delocalisation and the design of novel mastoparan analogues: enhanced
      cytotoxicity and secretory efficacy of [Lys5, Lys8, Aib10]MP.
AB  - The formation of an amphipathic helix is a major determinant of the biological
      activity of the tetradecapeptide mastoparan (MP). To address the functional
      significance of lysyl residues at positions 4, 11 and 12 of MP, we synthesised
      five novel analogues using sequence permutation and arginine-substitution to
      delocalise cationic charge. Comparative bioassays determined cytotoxicity, beta
      hexoseaminidase secretory efficacy and peptide-activated extracellular receptor
      stimulated kinase (ERK)1/2 phosphorylation. The monosubstitution of individual
      lysine residues with arginine produced differential changes to the indices of
      cytotoxicity and secretion indicating that these conservative substitutions are
      compatible with membrane translocation and the selective binding and activation
      of intracellular proteins. More profound changes to the predicted hydrophilic
      face of MP, resulting from the relocation or substitution of additional lysyl
      residues, enhanced both the cytotoxicity and secretory efficacy of novel
      peptides. Significantly, the more amphipathic peptide [Lys5, Lys8, Aib10]MP was
      identified to be both the most cytotoxic and the most potent secretagogue of all
      the peptides compared here. Charge delocalisation within the hydrophilic face of
      MP analogues was also compatible with peptide-induced activation of ERK1/2
      phosphorylation. Our data indicate that charge delocalisation is a suitable
      strategy to engineer more potent analogues of MP that differentially target
      intracellular proteins.

PMID- 15256283
TI  - The relationship between urotensin II plasma immunoreactivity and left
      ventricular filling pressures in coronary artery disease.
AB  - The role of urotensin II (U-II)--a vasoactive, mitogenic, and inotropic, peptide-
      in the pathophysiology of heart failure is controversial. The present study
      explores the relationship between plasma U-II immunoreactivity (U-IIIR) and
      hemodynamics in patients with coronary artery disease (CAD). Thirty-six patients
      with CAD-3 undergoing coronary artery bypass grafting (CABG) with cardiopulmonary
      bypass (CPB) and 36 medical patients (MED group) with CAD-1 to CAD-3 during right
      heart catheterization were studied. Significant correlations were observed
      between pulmonary capillary wedge pressure (PCWP) and U-IIIR--determined by
      enzyme immunoassay (EIA)--before (rho = 0.83) and after (rho = 0.6)
      cardiopulmonary bypass in the CABG group. With the exception of the CPB period,
      CABG patients with increased PCWP before CPB had higher U-II(IR) concentrations
      throughout the procedure. Significant correlations were observed between U-IIIR,
      proANP, proBNP, and mean right ventricular pressure (RVPM) in MED patients. No
      correlation was detectable between U-IIIR and PCWP. However, MED patients with
      CAD-3 (n = 13) had higher levels of U-IIIR, NTproANPIR (RIA), NTproBNPIR (EIA)
      and higher cardiac filling pressures than patients with CAD-1 (n = 13). These
      findings support an association between plasma U-IIIR levels and diastolic
      myocardial dysfunction in ischemic heart failure. The discrepancies regarding
      left and right cardiac filling pressures and U-IIIR levels in CABG and MED
      patients require further evaluation.

PMID- 15256284
TI  - Glucagon-like peptide 2 improves intestinal wound healing through induction of
      epithelial cell migration in vitro-evidence for a TGF--beta-mediated effect.
AB  - BACKGROUND/AIMS: In vitro studies suggest that glucagon-like peptide 2 (GLP-2),
      secreted from enteroendocrine cells in the gastrointestinal tract after food
      intake, is able to ameliorate mucosal injury in settings of human disease
      characterized by injury and dysfunction of the intestinal mucosal epithelium. We
      evaluated this potential of GLP-2 after epithelial trauma by using two in vitro
      models measuring intestinal epithelial cell proliferation and cell migration.
      MATERIALS AND METHODS: Injuries were induced in confluent monolayers of the small
      intestinal cells lines IEC-6 and IEC-18, as well as in the colonic cell lines
      Caco-2 and Colo 320. GLP-2 (50-500 nM) or other peptides were added to the media.
      Wound healing was investigated after 24 h by quantification of the number of
      cells migrating across the wound edge. Proliferation of cells was assessed by
      using photometric mitochondrial incorporation measurement of MTT (3-[4,5
      Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide). Monoclonal TGF-beta
      antibodies were added to wounded monolayers to examine whether the GLP-2-induced
      wound healing was TGF-beta-mediated. RESULTS: Migration assessments revealed a
      significant stimulation of GLP-2-induced migration in IEC-6 and IEC-18 monolayers
      compared to the placebo group. No effect was observed in the colon cancer cell
      lines Caco-2 and Colo 320. Results of the proliferation assays show a significant
      inhibition of proliferation by GLP-2 in small intestinal cell lines whereas a
      dose-dependent stimulation of proliferation in colonic epithelial cells was
      observed. Addition of neutralizing TGF-beta1 antibodies to wounded IEC-6 and IEC
      18 monolayers incubated with GLP-2 significantly reduced the number of migrating
      cells to the level of the placebo group. CONCLUSIONS: In our in vitro model, it
      was shown that the GLP-2-induced improvement of intestinal wound healing is TGF
      beta-mediated. These effects were predominant in the epithelium of the small
      intestine compared to colonic epithelium. Our findings provide further insight
      into mechanisms leading to GLP-2-induced mucosal wound healing. These results
      suggest that GLP-2 or analogues of this peptide may potentially be useful for the
      treatment of intestinal disorders characterized by injury and ineffective repair
      of the intestinal mucosa.

PMID- 15256285
TI  - A novel role for cholecystokinin: regulation of mesenteric vascular resistance.
AB  - The aim of this work was to characterize the vasoactive effect of cholecystokinin
      on mesenteric vasculature. The mesenteric vascular bed of 3-month-old Sprague
      Dawley rats was isolated and perfused at constant flow and changes in perfusion
      pressure monitored. CCK peptides lacked any direct contractile or relaxing effect
      on the mesenteric smooth muscle. Transmural nerve stimulation (TNS, 200 mA, 0.2
      ms, 8 and 16 Hz) elicited an increase in perfusion pressure reflecting
      contraction of the bed and CCK inhibited neurogenic contractions elicited by 8
      and 16 Hz TNS. The inhibition of neurogenic contractions was blocked by the CCK2
      receptor (CCK2R) antagonist, L-365,260 (10 and 100 nM), but not by the CCK1R
      antagonist, SR-27897. The inhibition of neurogenic contractions was reversed by
      the non-specific NOS inhibitor, L-NAME as well as by the specific nNOS inhibitor,
      S-methyl-L-thiocitrulline. In whole-mount segments of mesenteric arteries, CCK2R
      was detected in the adventitia, in nerve terminals, where it co-localized with
      synaptophysin and nNOS. CCK-8 immunoreactive fibers were also detected. These
      results suggest that CCK mediates vasodilatation of the mesenteric vascular bed
      through the release of NO via its presynaptic CCK2R. Our findings provide, for
      the first time, a neural mechanism by which CCK may increase mesenteric blood
      flow.

PMID- 15256286
TI  - CART peptide: central mediator of leptin-induced adipose tissue apoptosis?
AB  - Because of connections between CART peptide containing neurons and the
      sympathetic nervous system (SNS) and the possible role of the SNS in leptin
      induced adipose apoptosis, CART may act as a downstream effector of leptin
      induced adipose apoptosis. Male Sprague-Dawley rats received continuous
      intracerebroventricular (i.c.v.) infusion for 4 days of either artificial
      cerebrospinal fluid (aCSF, 12 microl/day), leptin (15 microg/day), or CART55-102
      at 2.4 microg/day (CART2.4) or 9.6 microg/day (CART9.6). Food intake (FI) was
      decreased 10.8% for CART2.4, 41.9% for CART9.6 and 33.4% for leptin (p<0.05).
      CART9.6 and leptin reduced meal size and meal number. Body weight (BW) was
      reduced by CART9.6 (14.6%) and leptin (11.6%) (p<0.05), but not by CART2.4.
      CART9.6 and CART2.4, but not leptin, caused hypothermia, and CART9.6 inhibited
      physical activity (p<0.05). Epididymal, inguinal and retroperitoneal fat pad
      weights were reduced (p<0.05) by both CART treatments and leptin; CART9.6 also
      reduced gastrocnemius muscle weight (18.1%, p<0.05). Leptin, but not CART,
      increased serum free fatty acid concentrations by 31.1% (p<0.05) and increased
      adipose apoptosis by 48% (p<0.05). These data show that although leptin and
      CART55-102 have some similar actions, CART55-102 is probably not a mediator for
      leptin-induced adipose apoptosis in the brain.

PMID- 15256287
TI  - Leptin and prolactin modulate the expression of SOCS-1 in association with
      interleukin-6 and tumor necrosis factor-alpha in mammary cells: a role in
      differentiated secretory epithelium.
AB  - Leptin and its receptors have been shown to be expressed in several tissues,
      suggesting that this protein might be effective not only at the CNS level but
      also peripherally. We have previously reported that leptin and its long form
      receptor are expressed in the mouse mammary epithelial cell line HC11. In this
      study, we report a specific relationship among leptin, prolactin (PRL),
      interleukin-6 (IL-6), and tumor necrosis-alpha (TNF-alpha) in the modulation of
      the suppressor of cytokine signaling 1 (SOCS-1). Furthermore, we show that leptin
      and PRL are able to effectively enhance SOCS-1 gene expression in the HC11 cell
      line. Finally, high concentrations of leptin (100 nM) and/or PRL significantly
      (p<0.05) reduce the inhibitory effect of IL-6 (10 and 100 ng/ml) and TNF-alpha
      (10 and 100 ng/ml) on beta-casein gene expression in HC11 cells transfected with
      pbetacCAT, a chimeric rat-beta casein gene promoter-cloramphenicol acetyl
      transferase (CAT) gene construct. These results provide evidence that leptin may
      be an important mediator in regulating mammary gland growth and development and
      that this role may be related to the immune factors that are involved in
      inflammation.

PMID- 15256288
TI  - Suicide in doctors. A psychological autopsy study.
AB  - OBJECTIVES: Doctors are at higher risk of suicide than many other occupational
      groups. This study was conducted to investigate factors associated with suicide
      in doctors. METHOD: Psychological autopsy study of 38 working doctors who died by
      suicide in England and Wales between January 1991 and December 1993. RESULTS:
      Psychiatric illness was present in 25 of the doctors. Depressive illness and drug
      or alcohol abuse were the most common diagnoses. Twenty-five doctors had
      significant problems related to work, 14 had relationship problems and 10 had
      financial problems. Multiple and interrelated problems were often present. The
      most common method of suicide was self-poisoning, often with drugs taken from
      work. CONCLUSION: Prevention of suicide in doctors requires a range of
      strategies, including improved management of psychiatric disorder, measures to
      reduce occupational stress and restriction of access to means of suicide when
      doctors are depressed.

PMID- 15256289
TI  - Neurocognitive function and quality of life in relation to hematocrit levels in
      chronic hemodialysis patients.
AB  - OBJECTIVE: We examined the putative association between the levels of hematocrit
      and improvement of cognitive function as well as quality of life in patients with
      end-stage renal disease (ESRD). METHODS: Fifty-six ESRD patients were divided
      into two groups according to their hematocrit levels: Group A consisted of 28
      patients with hematocrit levels lower than the median (27.2 g%), while Group B,
      the remaining 28 patients, with higher than the median level. Neurocognitive
      function and the quality of life in these two groups were compared. RESULTS:
      Although patients with higher hematocrit levels scored better in the
      neurocognitive function tests such as the forward digit-span (P=.034) and digit
      symbol (P=.023), their quality of life evaluated by three scales (Karnofsky
      Scale, Index of Well-Being, and SF-36) was not any better than those with lower
      hematocrit group. CONCLUSIONS: The present study indicated that in chronic
      hemodialysis patients, the higher hematocrit levels improve neurocognitive
      function but not the quality of life.

PMID- 15256290
TI  - The presence of psychiatric disorders reduces the likelihood of neurologic
      disease among referrals to a neurology clinic.
AB  - OBJECTIVES: This study aims to explore the prevalence and impact of psychiatric
      disorders on the likelihood of an organic, neurological explanation for symptoms
      among neurology referrals. METHODS: Consecutive new adult neurology referrals
      were screened for psychiatric disorders (PRIME-MD) prior to evaluation by
      neurologists, blinded to these results. Diagnoses were stratified into three
      categories: no neurological diagnosis, neurological-headache, and neurological
      nonheadache. RESULTS: Of 235 patients enrolled, 79 (34%) received no neurological
      diagnosis, 54 (23%) headache and 102 (43%) a neurological diagnosis. Overall, 39%
      had an underlying psychiatric disorder. Patients with psychiatric disorders were
      less likely to have a neurological diagnosis (RR: 0.66, 95% CI: 0.48-0.90): 25%
      of patients with a neurological diagnosis had an underlying psychiatric disorder,
      compared to 43% among those with no diagnosis and 57% among those with headaches.
      CONCLUSION: Psychiatric disorders are common among neurology referrals,
      particularly those with headaches and are associated with a decreased likelihood
      of an underlying neurological process.

PMID- 15256291
TI  - A brief diagnostic screening instrument for mental disturbances in general
      medical wards.
AB  - OBJECTIVE: Mental illness is prevalent among general hospital ward patients but
      often goes unrecognised. The aim of this study was to validate the SCL-8d as a
      brief questionnaire for mental disturbances for use in general hospitals.
      METHODS: The study included 2040 patients, 18 years or older, consecutively
      admitted to 11 general internal medicine wards in seven European countries. All
      patients were screened on admission by means of the SCL-8d questionnaire. The
      psychometric performance (i.e., the internal validity) of the SCL-8d scale was
      tested using modern item response theory (IRT) in the form of the Rasch model.
      RESULTS: Differences between sample characteristics were considerable. Even so,
      the SCL-8d scale showed a remarkable, statistically significant fit in terms of
      internal homogeneity (P>.01) in all individual settings, except in Spain and
      Germany where the item "Everything is an effort" had to be excluded to obtain a
      fit. When pooling data from all centres, an excellent statistical significance of
      fit (P>.05) was obtained by exclusion of the "Effort" item. The scale was
      homogeneous as to gender (P>.05), but not age as it performed better among young
      patients than among patients older than 60 years (P<.01). In these two patient
      groups both internal and external homogeneity (gender, median age) was achieved.
      The SCL-8d sum score showed a marked correlation with current and previous
      treatment for mental illness. CONCLUSION: Apart from the "Effort" item ranking
      differently on the latent severity dimension as to age, the SCL-8d seems very
      robust from a psychometric point of view. Besides being short, the SCL-8d scale
      contains only emotional symptoms. It would therefore seem to be an excellent
      diagnostic tool for use in medical settings.

PMID- 15256292
TI  - Temporal stability and differential relationships with neuroticism and
      extraversion of the three subscales of the 20-item Toronto Alexithymia Scale in
      clinical and nonclinical samples.
AB  - OBJECTIVES: To examine the cross-sample and temporal stability of the three
      subscales of the 20-item Toronto Alexithymia Scale (TAS-20) and to study the
      pattern of associations between the TAS-20 scales, neuroticism, and alexithymia.
      METHODS: Two clinical and three nonclinical samples were included in the cross
      sectional part of the study. One clinical and one nonclinical sample also
      participated in the 6-month follow-up study. To test the replicability of the
      three-factor structure of the TAS-20 across samples, a principal component
      analysis was conducted, followed by a Procrustes rotation. Linear regression
      analyses were conducted to examine temporal stability and to determine the
      specificity of the associations among the TAS-20 scales, neuroticism, and
      extraversion. RESULTS: The three-factor structure of the TAS-20 was confirmed
      across all five samples. With a few exceptions, neuroticism and extraversion
      attained a higher level of temporal stability than the alexithymia scales. The
      TAS-subscale measuring difficulty identifying feelings (DIF) was less stable in
      the clinical than in the nonclinical sample. Neuroticism was most strongly
      associated with DIF, whereas extraversion was mainly related to externally
      oriented thinking (EOT). A combination of both neuroticism and extraversion was
      the best predictor of difficulty describing feelings (DDF). CONCLUSIONS: Future
      studies on the psychometric properties and the clinical value of the TAS-20
      should pay more attention to its subscales. Especially the EOT facet needs
      further examination.

PMID- 15256293
TI  - Mindfulness-based stress reduction and health benefits. A meta-analysis.
AB  - OBJECTIVE: Mindfulness-based stress reduction (MBSR) is a structured group
      program that employs mindfulness meditation to alleviate suffering associated
      with physical, psychosomatic and psychiatric disorders. The program, nonreligious
      and nonesoteric, is based upon a systematic procedure to develop enhanced
      awareness of moment-to-moment experience of perceptible mental processes. The
      approach assumes that greater awareness will provide more veridical perception,
      reduce negative affect and improve vitality and coping. In the last two decades,
      a number of research reports appeared that seem to support many of these claims.
      We performed a comprehensive review and meta-analysis of published and
      unpublished studies of health-related studies related to MBSR. METHODS: Sixty
      four empirical studies were found, but only 20 reports met criteria of acceptable
      quality or relevance to be included in the meta-analysis. Reports were excluded
      due to (1) insufficient information about interventions, (2) poor quantitative
      health evaluation, (3) inadequate statistical analysis, (4) mindfulness not being
      the central component of intervention, or (5) the setting of intervention or
      sample composition deviating too widely from the health-related MBSR program.
      Acceptable studies covered a wide spectrum of clinical populations (e.g., pain,
      cancer, heart disease, depression, and anxiety), as well as stressed nonclinical
      groups. Both controlled and observational investigations were included.
      Standardized measures of physical and mental well-being constituted the dependent
      variables of the analysis. RESULTS: Overall, both controlled and uncontrolled
      studies showed similar effect sizes of approximately 0.5 (P<.0001) with
      homogeneity of distribution. CONCLUSION: Although derived from a relatively small
      number of studies, these results suggest that MBSR may help a broad range of
      individuals to cope with their clinical and nonclinical problems.

PMID- 15256294
TI  - Breast cancer patients have improved immune and neuroendocrine functions
      following massage therapy.
AB  - OBJECTIVES: Women with breast cancer are at risk for elevated depression,
      anxiety, and decreased natural killer (NK) cell number. Stress has been linked to
      increased tumor development by decreasing NK cell activity. The objectives of
      this study included examining massage therapy for women with breast cancer for
      (1) improving mood and biological measures associated with mood enhancement
      (serotonin, dopamine), (2) reducing stress and stress hormone levels, and (3)
      boosting immune measures. METHODS: Thirty-four women (M age=53) diagnosed with
      Stage 1 or 2 breast cancer were randomly assigned postsurgery to a massage
      therapy group (to receive 30-min massages three times per week for 5 weeks) or a
      control group. The massage consisted of stroking, squeezing, and stretching
      techniques to the head, arms, legs/feet, and back. On the first and last day of
      the study, the women were assessed on (1) immediate effects measures of anxiety,
      depressed mood, and vigor and (2) longer term effects on depression, anxiety and
      hostility, functioning, body image, and avoidant versus intrusive coping style,
      in addition to urinary catecholamines (norepinephrine, epinephrine, and dopamine)
      and serotonin levels. A subset of 27 women (n=15 massage) had blood drawn to
      assay immune measures. RESULTS: The immediate massage therapy effects included
      reduced anxiety, depressed mood, and anger. The longer term massage effects
      included reduced depression and hostility and increased urinary dopamine,
      serotonin values, NK cell number, and lymphocytes. CONCLUSIONS: Women with Stage
      1 and 2 breast cancer may benefit from thrice-weekly massage therapy for reducing
      depressed mood, anxiety, and anger and for enhancing dopamine, serotonin, and NK
      cell number and lymphocytes.

PMID- 15256295
TI  - The attitude toward truth telling of cancer in Taiwan.
AB  - OBJECTIVE: This study examined a group of Taiwanese subjects at a medical
      university hospital regarding their attitudes toward truth telling of cancer.
      METHOD: Self-report survey with convenience sampling of 195 participants admitted
      for a 3-day comprehensive health examination in a medical university hospital in
      Taiwan. Three instruments used to collect the data included the Brief Psychiatric
      Symptom Rating Scale (BPSRS), Chinese Health Questionnaire (CHQ), and the
      Attitude Toward Truth Telling of Cancer List. RESULTS: Once diagnosed with
      cancer, 92.3% of the participants preferred being told the truth about their
      diagnosis and 7.7% did not. Age, education, and employment were found to differ
      between disclosure and nondisclosure groups. The latter group also tended to have
      higher depression and hostility scores on the BPSRS and higher minor psychiatric
      morbidity scores. A total of 62.6% of the participants preferred that doctors
      tell a relative the truth about their cancer diagnosis, while 37.4% preferred
      that doctors not tell a relative the truth. The distributions of demographic data
      and mental status did not significantly differ between disclosure and
      nondisclosure groups if a relative was to be the cancer victim. CONCLUSIONS: A
      majority of subjects in Taiwan would prefer to know the truth if victimized by a
      cancer disease, despite the supposed influence of Chinese culture. Furthermore,
      attitudes toward truth telling of cancer differed between relatives of patients
      and the patients themselves. Relatives of cancer patients were more likely to
      follow to the principle of beneficence, whereas the patients themselves were more
      likely to follow to the principle of autonomy.

PMID- 15256296
TI  - Psychometric properties and normative data of the Eating Disorder Inventory among
      12 to 18 year old Chinese girls in Hong Kong.
AB  - The present study examined the psychometric properties of the Eating Disorder
      Inventory (EDI) among Chinese adolescent girls in Hong Kong. We also attempted to
      provide normative data for the EDI among 12- to 18-year-old Chinese girls in Hong
      Kong. Two thousand two hundred and fifty-six high school girls between the age of
      12 and 18 years participated in this study. Subjects completed the questionnaire
      package anonymously at their schools. Findings indicate that the internal
      consistency estimates for the eight EDI scales were in the acceptable range, with
      alpha ranging from 0.68 for Perfectionism to 0.87 for Body Dissatisfaction. With
      the exception of a few items, the item-total correlations were also acceptable
      for the eight scales. Findings of the principal components analysis support the
      original eight clinically derived EDI constructs. Group comparison analyses
      reveal significant age differences and race differences in several EDI scales.
      EDI percentile scores are presented for girls 12-13 and 14-18 years of age in the
      present study. This study provides further empirical support to the transcultural
      validity of the EDI. It also highlights the importance of establishing age- and
      race-specific norms for the inventory.

PMID- 15256297
TI  - Application of Prochaska's transtheoretical model of change to patients with
      eating disorders.
AB  - OBJECTIVE: Although eating disorders cause severe somatic and psychological
      sequelae, a majority of affected patients are not motivated for treatment. The
      aim of this study was to assess stages of change in patients with eating
      disorders and to analyze their correlations with clinical characteristics and
      treatment processes using Prochaska's transtheoretical model of change. METHODS:
      A consecutive sample (N=88) including outpatients suffering from anorexia (n=29),
      bulimia (n=32), and eating disorders not otherwise specified (n=27) was recruited
      from an eating disorders clinic with a low-threshold access. The patients'
      readiness to change their eating behavior was assessed by a self-rating scale
      (URICA), and a score for each participant on each subscale (precontemplation,
      contemplation, action) was derived from the scale. Patients were introduced to a
      set of eight treatment processes over the course of four treatment sessions.
      During the four sessions, therapists rated whether or not patients appeared to be
      using each of the treatment processes. RESULTS: While diagnostic subtype, age,
      illness duration, and previous treatments were not associated with motivational
      stages, self-referral was positively correlated to treatment motivation.
      Emotional involvement, specific behavioral change processes, and beginning a
      continuing treatment were correlated with more advanced stages of change.
      CONCLUSION: This study supports the notion of the stages of change as an
      independent dimension that is relevant for the treatment of eating disorders. The
      lack of impact of previous, presumably nonspecific treatments on the stages of
      change underlines the importance to assess and to improve specifically patients'
      motivation. Therapeutic work towards the mobilisation of emotions with regard to
      their eating problem as a means to improve readiness to change should be examined
      in future studies.

PMID- 15256298
TI  - A word-stem completion task to assess implicit processing of appearance-related
      information.
AB  - OBJECTIVE: This paper reports on the development and utility of a new implicit
      measure of appearance-related information processing. METHODS: A 20-item word
      stem completion task was constructed, in which each word stem could be completed
      with either an appearance-related word or at least one non-appearance
      alternative. The measure was tested in four different experiments, most
      investigating the impact of acute exposure to media-portrayed thin idealised
      female images. RESULTS: Exposure to media images or other appearance-related
      material led to the generation of more appearance- or weight-related words in
      both female and male samples. CONCLUSION: It was concluded that the word-stem
      task has empirical utility as a simple, self-paced and sensitive outcome measure
      in experimental studies of media exposure. We conceptualise the word-stem task as
      a measure of appearance- and weight-schema activation.

PMID- 15256299
TI  - What if my back breaks? Making sense of musculoskeletal pain among South Asian
      and African-Caribbean people in the North West of England.
AB  - OBJECTIVES: The pain and disability, which arise as a result of musculoskeletal
      conditions, have been central to theories and understanding about chronic
      illness. However, little attention has been paid to the experience of such pain
      amongst ethnic minority groups. In this paper, we explore Asian and African
      Caribbean respondents' ideas about the nature of and management of widespread
      pain. METHODS: Our data are drawn from a qualitative study linked to an
      epidemiological study of musculoskeletal symptoms undertaken in the North West of
      England. In-depth interviews were carried out with 32 people. Themes identified
      from the data were causes of symptoms, experience of pain, primary care
      utilisation and self-management. RESULTS: For both African-Caribbean and South
      Asian populations widespread pain was reported more frequently than a general
      population sample residing in the same locality. However, notions of the
      experience and management of widespread pain differed. Accounts of pain from the
      African-Caribbean respondents coincided with a traditional Western medical model
      of psychogenic pain and individualised coping strategies. Descriptions from some
      South Asian respondents suggested a lack of demarcation between pain located in
      specific parts of the body and broader social and personal concerns and an
      unwillingness to recognise the latter as "depression" or psychological distress.
      Help from family members was referred to more than individual strategies of
      managing pain. CONCLUSIONS: Differences in the experience of musculoskeletal has
      relevance for understanding the way in which psychosocial distress is manifested
      and managed in primary care.

PMID- 15256300
TI  - A randomised controlled trial of a psycho-educational intervention to aid
      recovery in infectious mononucleosis.
AB  - OBJECTIVES: Glandular fever is associated with an approximate fivefold increase
      in fatigue at 6 months. Reduced levels of fitness and illness beliefs may be
      important predictors of fatigue following glandular fever. We therefore developed
      a brief psycho-educational intervention aimed at improving recovery from
      infectious mononucleosis, and piloted a randomised controlled trial to evaluate
      the intervention. METHODS: We performed a randomised-controlled trial in primary
      health care in Southeast London and Kent. Sixty-nine patients aged between 16 and
      45 years who were diagnosed, serologically and clinically, with acute infectious
      mononucleosis between December 1999 and December 2000 were randomised. The
      control group received a standardised fact-sheet about infectious mononucleosis,
      which gave no advice on rehabilitation. Patients who were randomised to the
      intervention received an individual treatment session, two follow-up telephone
      calls, and an information booklet. Fatigue score 6 months after the onset of
      infectious mononucleosis was the main outcome measure. RESULTS: Sixty-nine out of
      139 patients referred were recruited and randomised. Eighty-seven percent of
      those recruited completed the Fatigue Questionnaire at 6 months. The intervention
      was acceptable to all who received it. There were fewer fatigue cases in the
      intervention group than the control group at 6 months follow-up (odds ratio 0.31,
      95% confidence interval 0.09-0.91). CONCLUSIONS: A brief intervention at the
      diagnosis of infectious mononucleosis is acceptable, and may help prevent the
      development of chronic fatigue. Definitive randomised controlled trials are
      required to test the intervention.

PMID- 15256301
TI  - Psychopathology and behavioural trends of children with accidental poisoning.
AB  - OBJECTIVE: To study the psychopathology of both young children with accidental
      poisoning and their mothers, measure the poisoned children's trends of behaviour
      and explore whether there is an association between parental smoking and
      poisoning in children. METHODS: The psychopathology of 150 poisoned and 150
      matched control young children, and their mothers was studied according to DSM-IV
      criteria. Children's perceptions of behaviour were examined by a measure
      assessing internalizing and externalizing behaviour. RESULTS: Psychiatric
      disorders were by 4.3-fold more frequent in the poisoned than in the control
      children. Also, the study children exhibited higher levels in all aspects of
      behaviour. In the poisoned children's mothers the frequency of psychiatric
      disorders was threefold greater than in the control. Also, "parent-child
      relational problem" and "psychosocial and environmental problems" were more
      frequent in the study than the control groups. Smoking was more frequent in both
      parents of the poisoned than of the control children. CONCLUSIONS: Findings show
      that risk factors for accidental poisoning are localized on the children, their
      parents or may have a psychosocial-environmental origin. The presence of certain
      psychiatric disorders in young children (attention-deficit and disruptive
      behaviour disorders) or their mothers (anxiety, personality and mood disorders)
      requires the implementation of early measures for reducing the risk of poisoning.

PMID- 15256302
TI  - A 7-year prospective quasi-experimental study of the effects of removing dental
      amalgam in 76 self-referred patients compared with 146 controls.
AB  - BACKGROUND: Dental amalgam has been suggested to cause long-term physical and
      mental problems. Claims that removal of the amalgam may lead to dramatic
      improvements in health have not been tested empirically in controlled studies
      with a long follow-up period. PURPOSE: To investigate the long-term effects of
      removal of dental amalgam on physical and mental symptoms in self-referred
      patients who complained of multiple somatic and mental symptoms attributed to
      dental amalgam fillings. METHODS: In a quasi experimental study, changes in the
      mental and physical symptoms in 76 patients who had their dental amalgam removed
      7 years ago were compared with changes in symptoms among patients with known
      chronic medical disorders seen in alternative (n=51) and ordinary (n=51) medical
      family practices and noncomplaining patients with similar amounts of dental
      amalgam fillings (n=44) seen in an ordinary dental practice. The assessments
      included written self-reports, a 131-item somatic symptom checklist, Eysenck
      Personality Questionnaire (EPQ), the General Health Questionnaire (GHQ) and
      Toronto Alexithymia Scale (TAS). RESULTS: Subjects who removed their dental
      amalgam reported reduced physical and mental symptom load compared to status
      prior to removal, but only to a level comparable with that reported by the other
      groups with chronic medical disorders. The dental control group consistently
      reported lower symptom load during the whole period. In a hierarchical three-step
      regression model, pretreatment physical symptom load (P<.01), age (P<.10) and
      removal of dental amalgam (ns) predicted 26% of the variance in posttreatment
      physical symptom load. CONCLUSION: In a self-referred group of subjects with
      health complaints attributed to dental amalgam who remove their dental amalgam,
      the symptom load at follow-up corresponds to the level seen in chronic medical
      disorders despite the strong implicit placebo effect of the present quasi
      experimental design. The finding does not support the hypothesis that removal of
      dental amalgam will reduce health complaints to normal levels and seriously
      questions the hypothesis that dental amalgam is an important cause of distress
      and health complaints.

PMID- 15256303
TI  - Hormonal correlates of dominance in meerkats (Suricata suricatta).
AB  - In cooperatively breeding meerkats (Suricata suricatta), individuals typically
      live in extended family groups in which the dominant male and female are the
      primary reproductives, while their offspring delay dispersal, seldom breed, and
      contribute to the care of subsequent litters. Here we investigate hormonal
      differences between dominants and subordinates by comparing plasma levels of
      luteinizing hormone (LH), estradiol and cortisol in females, and testosterone and
      cortisol in males, while controlling for potential confounding factors. In both
      sexes, hormone levels are correlated with age. In females, levels of sex hormone
      also vary with body weight and access to unrelated breeding partners in the same
      group: subordinates in groups containing unrelated males have higher levels of LH
      and estradiol than those in groups containing related males only. When these
      effects are controlled, there are no rank-related differences in circulating
      levels of LH among females or testosterone among males. However, dominant females
      show higher levels of circulating estradiol than subordinates. Dominant males and
      females also have significantly higher cortisol levels than subordinates. Hence,
      we found no evidence that the lower levels of plasma estradiol in subordinate
      females were associated with high levels of glucocorticoids. These results
      indicate that future studies need to control for the potentially confounding
      effects of age, body weight, and access to unrelated breeding partners before
      concluding that there are fundamental physiological differences between dominant
      and subordinate group members.

PMID- 15256304
TI  - Progestins and place preference conditioning after paced mating.
AB  - When female rats pace their coital interaction, a reward state evaluated by
      conditioned place preference is induced. Progesterone (P) is essential for the
      expression of proceptive behavior and for the induction of CPP. However, the
      functional significance of ring A reduction of P for the induction of this state
      during estrous is unsettled. In the present study, we evaluated whether ring A
      reduced metabolites of P are involved in the reward state induced when the
      females are allowed to pace their sexual contacts. Ovariectomized (ovx) female
      rats treated with estradiol benzoate (EB, 5 microg) and P (13 microg), Megestrol
      acetate (MA; 13 microg ), 5 alpha-pregnan-20 dione (5 alphaDHP; 3 microg), or 5
      beta-pregnan-3 alpha-ol-20-one (5 beta,3 alpha-Pgl; 3 microg) were used.
      Progestins were dissolved in propylene glycol and intravenously (iv) injected
      through an indwelling jugular catheter before females were tested for pacing
      behavior. After 15 intromissions or one ejaculation, females were gently placed
      in the nonpreferred compartment of a CPP box. Paced mating in all groups treated
      with progestins induced a clear change of preference. The administration of
      progestins alone did not induce CPP. These results suggest that P and ring A
      reduced metabolites facilitate the reward state following pacing.

PMID- 15256305
TI  - Different effects of subchronic doses of 17-beta estradiol in two ethologically
      based models of anxiety utilizing female rats.
AB  - Estrogen may have differing effects on 'anxiety' responses under different
      conditions. The current study tested the effects of estrogen on anxiety-like
      behavior when administered for 6-7 days in ovariectomized (OVX) female rats. Two
      animal paradigms were utilized; the elevated plus maze (EPM), measuring changes
      in innate fear of exploration of open spaces; and the social interaction test
      (SIT), measuring the exploration of a novel, same gender partner. In the EPM,
      estradiol-treated OVX females both entered and spent more time in the open arms
      than control OVX females, indicating an anxiolytic-like action of estradiol. In
      contrast, estradiol treated OVX females interacted less with the partner animal
      in the SIT compared with controls suggesting anxiogenic-like effects. The
      possible anxiogenic effect of estradiol in the SIT is supported by two findings:
      (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did
      not affect locomotion and therefore, the reduced social interaction is not due to
      reduced activity. Acute administration of progesterone (5 mg/kg), which has
      anxiolytic properties, did not reverse estradiol-induced social interaction
      deficits, suggesting that lack of progesterone did not account for estradiol's
      anxiogenic effects. These results, while seemingly contradictory when interpreted
      within a unified concept of anxiety, may well reflect the ethological roles of
      reproductive hormones and their effects on different types of exploratory
      anxiety.

PMID- 15256306
TI  - Testosterone reduces responsiveness to nociceptive stimuli in a wild bird.
AB  - The hormone testosterone (T) is involved in the control of aggressive behavior in
      male vertebrates. T enhances the frequency and intensity of aggressive behaviors
      during competitive interactions among males. By promoting high-intensity
      aggression, T also increases the risk of injury and presumably the perception of
      painful stimuli. However, perception of painful stimuli during fights could
      counteract the expression of further aggressive behavior. We therefore
      hypothesize that one function of T during aggressive interactions is to reduce
      nociception (pain sensitivity). Here, we experimentally document that T indeed
      reduces behavioral responsiveness to a thermal painful stimulus in captive male
      house sparrows (Passer domesticus). Skin nociception was quantified by foot
      immersion into a hot water bath, a benign thermal stimulus. Males treated with
      exogenous testosterone left their foot longer in hot water than control birds.
      Conversely, males in which the physiological actions of testosterone were
      pharmacologically blocked withdrew their foot faster than control birds.
      Testosterone might exert its effects on pain sensitivity through conversion into
      estradiol in the dorsal horn of the spinal cord. Decreased nociception during
      aggressive encounters may promote the immediate and future willingness of males
      to engage in high-intensity fights.

PMID- 15256307
TI  - Consequences of elevating plasma testosterone in females of a socially monogamous
      songbird: evidence of constraints on male evolution?
AB  - To explore whether selection for testosterone-mediated traits in males might be
      constrained by costs of higher testosterone to females, we examined the effects
      of experimental elevation of plasma testosterone on physiological, reproductive,
      and behavioral parameters in a female songbird, the dark-eyed junco (Junco
      hyemalis). We used subcutaneous implants to elevate testosterone (T) in captive
      and free-living female juncos. In captive birds, we measured the effects of high
      T on body mass, feather molt, and brood patch formation. In the field, we
      monitored its effects on the timing of egg laying, clutch size, egg size, egg
      steroid levels, incubation, and nest-defense behavior. Females implanted with
      testosterone (T-females) had significantly higher circulating levels of
      testosterone than did control females (C-females). Captive T-females had lower
      body mass, were less likely to develop brood patches, and delayed feather molt
      relative to C-females. Among free-living females, the interval between nest
      completion and appearance of the first egg was longer for T-females than for C
      females and egg yolk concentrations of testosterone were higher, but there were
      no significant differences in estradiol levels, clutch size, or egg size.
      Incubation and nest defense behavior were also similar between T- and C-females.
      Our results suggest that selection on males for higher testosterone might
      initially lead to a correlated response in females producing changes in body mass
      and feather molt, both of which could be detrimental. Other possible female
      responses would be delayed onset of reproduction, which might reduce reproductive
      success, and higher yolk testosterone, which might have either positive or
      negative effects on offspring development. We found no reason to expect reduced
      parental behavior by females as a negative fitness consequence of selection for
      higher testosterone in males.

PMID- 15256308
TI  - European starling chicks benefit from high yolk testosterone levels during a
      drought year.
AB  - Avian egg yolk contains androgenic hormones, such as testosterone, of maternal
      origin. Experimental elevation of yolk testosterone levels enhances growth of
      canary chicks. Success in sibling competition, due to increased begging, is
      presumed to underlie this growth enhancement, because canary hatchlings from
      testosterone-treated eggs beg longer in response to vibrational stimuli than
      controls. Furthermore, experimental elevation of both yolk androstenedione and
      testosterone increased chick growth and begging in black-headed gulls. We
      measured daily growth of European starling (Sturnus vulgaris) chicks hatching
      from testosterone-treated or vehicle-treated (control) eggs until 14 days of age,
      and measured begging behavior at hatching and at 5 days of age. A temporary
      drought caused relatively high levels of early brood reduction for this
      population; 2- and 3-day-old chicks were most likely to starve. We found that
      chicks from testosterone-treated eggs were less likely to starve than control
      chicks, and were heavier on the days when most brood reduction occurred. However,
      chicks from testosterone-treated eggs begged less than control chicks on the day
      of hatching, and begged similarly at 5 days of age. Thus, while yolk testosterone
      did increase growth during periods of (presumably) high competition, increased
      begging does not appear to mediate this effect. Instead, testosterone may induce
      more efficient energy use, for example, by decreasing ineffective begging. While
      our results indicate that elevated yolk testosterone enhances survival, and thus
      offspring and parental fitness, further evidence regarding the fitness
      consequences of yolk androgens are vital to understanding their role in avian
      life history.

PMID- 15256309
TI  - Long-term effects of pubertal anabolic-androgenic steroid exposure on
      reproductive and aggressive behaviors in male rats.
AB  - The current study examined acute and long-term effects of anabolic-androgenic
      steroid (AAS) exposure during puberty on copulation, vocalizations, scent
      marking, and intermale aggression, both with and without tail pinch, in intact
      male rats. Animals received 5 mg/kg of testosterone, nandrolone, stanozolol, or
      vehicle, beginning at puberty. After 5 weeks, behavior tests were performed while
      continuing AAS injections. AAS treatment was then discontinued. Behaviors were
      tested during 3-5 weeks, 9-11 weeks, and 15-17 weeks of withdrawal. During AAS
      administration, stanozolol males showed significant reductions in all behaviors
      compared with controls, except aggression with tail pinch. Nandrolone treatment
      significantly reduced vocalizations and scent marking, and testosterone had no
      significant effect on behavior. During withdrawal, behaviors in stanozolol males
      recovered to control levels at variable rates: aggression at 4 weeks; mounts,
      vocalizations, and scent marking at 9 weeks; and ejaculations at 15 weeks of
      withdrawal. Stanozolol males showed significantly higher levels of tail pinch
      induced aggression during every withdrawal test. Nandrolone-treated males scent
      marked at control levels by 9 weeks withdrawal but displayed significantly fewer
      vocalizations and significantly more tail pinch-induced aggression than controls
      for the entire study. Testosterone-treated males scent-marked significantly below
      controls at 3 weeks withdrawal and showed significantly more tail pinch-induced
      aggression at 5 weeks withdrawal. All three AAS significantly increased tail
      pinch-induced aggression compared with corresponding nontail pinch tests, even at
      study endpoint. These results suggest that alterations in androgen-dependent
      behaviors by pubertal AAS exposure can persist long after drug exposure, and some
      effects may even be permanent.

PMID- 15256310
TI  - Female sexual swelling size, timing of ovulation, and male behavior in wild West
      African chimpanzees.
AB  - Conspicuous swellings of the perineal skin can be observed in females of many
      catharrine primate species particularly during the middle stages of the ovarian
      cycle. The functional significance of this trait remains poorly understood.
      Recently, two hypotheses, the "reliable indicator" hypothesis and the "graded
      signal" hypothesis that take into account not only the pattern but also the
      exaggerated size of sexual swellings, have gained attention. Here we test several
      predictions made by these hypotheses by combining (i) direct size measures (from
      video captures) of female sexual swellings with (ii) urinary hormone data to
      indicate timing of ovulation through enzyme immunoassay measurements of estrone
      conjugates and pregnanediol glucuronide (PdG) and (iii) behavioral observations
      of male mating efforts throughout 36 ovulatory cycles in 12 wild chimpanzees. We
      are able to show that (i) even within the traditionally defined maximum swelling
      period, further slight increases in swelling size indicate approaching ovulation,
      and (ii) that male mating interest changes according to the changes in swelling
      size. Furthermore, absolute swelling size during the periovulatory period
      increases and the alpha male associates more with females as the number of cycles
      to conception decreases. Finally, when having the choice between several
      "maximally" tumescent females, the alpha male prefers the female that is in the
      fertile phase of her cycle rather than that with the biggest swelling at that
      time. Thus, most of our findings are in line with the predictions of the graded
      signal hypothesis while none of them would support the reliable indicator
      hypothesis.

PMID- 15256311
TI  - Alpha 1-microglobulin: clinical laboratory aspects and applications.
AB  - BACKGROUND: Urinary microproteins are becoming increasingly important in clinical
      diagnostics. They can contribute in the non-invasive early detection of renal
      abnormalities and the differentiation of various nephrological and urological
      pathologies. Alpha 1-microglobulin (A1M) is an immunomodulatory protein with a
      broad spectrum of possible clinical applications and seems a promising marker for
      evaluation of tubular function. METHOD: We performed a systematic review of the
      peer-reviewed literature (until end of November 2003) on A1M with emphasis on
      clinical diagnostic utility and laboratory aspects. CONCLUSIONS: A1M is a 27-kDa
      glycoprotein, present in various body fluids, with unknown exact biological
      function. The protein acts as a mediator of bacterial adhesion to polymer
      surfaces and is involved in inhibiting renal lithogenesis. Because A1M is not an
      acute phase protein, is stable in a broad range of physiological conditions and
      sensitive immunoassays have been developed, its measurement can be used for
      clinical purposes. Unfortunately, international standardisation is still lacking.
      Altered plasma/serum levels are usually due to impaired liver or kidney functions
      but are also observed in clinical conditions such as HIV and mood disorders.
      Urinary A1M provides a non-invasive, inexpensive diagnostic alternative for the
      diagnosis and monitoring of urinary tract disorders (early detection of tubular
      disorders such as heavy metal intoxications, diabetic nephropathy, urinary
      outflow disorders and pyelonephritis).

PMID- 15256312
TI  - Pathophysiology, prognostic significance and clinical utility of B-type
      natriuretic peptide in acute coronary syndromes.
AB  - The natriuretic hormones are a family of vasoactive peptides that can be measured
      circulating in the blood. Because they serve as markers of hemodynamic stress,
      the major focus of the use of natriuretic peptide levels [predominantly B-type
      natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the
      clinical diagnosis and management of congestive heart failure (CHF). Recently,
      however, the measurement of natriuretic peptides in the acute coronary syndromes
      (ACS) has been shown to provide information complementary to traditional
      biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK).
      Studies in several types of acute coronary syndromes [ST-segment elevation
      myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina
      (UA)] have shown that elevated levels of natriuretic peptides are independently
      associated with adverse outcomes, particularly mortality. Additional information
      is obtained from the use natriuretic peptides in combination with other markers
      of risk including biomarkers of necrosis and inflammation. This review will
      summarize the scientific rationale and clinical evidence supporting measurement
      of natriuretic peptides for risk stratification in acute coronary syndromes.
      Future research is needed to identify therapies of particular benefit for
      patients with ACS and natriuretic peptide elevation.

PMID- 15256313
TI  - Expression modes of urinary N-acetyl-beta-D-glucosaminidase in patients with
      chronic renal insufficiency.
AB  - BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity has emerged as
      potentially useful early marker of renal tubular injury. This activity is usually
      evaluated in random urine samples and is related to urinary creatinine
      concentration. Reports about the lack of correlation between NAG activity of 24-h
      urines and activity of random urine samples in some clinical and experimental
      situations led us to study the correlation existing between different procedures
      for expressing urinary NAG in patients with chronic renal insufficiency. METHODS:
      Thirty samples of 24-h urine and 30 random urine samples from chronic renal
      insufficiency patients were collected. The activity of urinary NAG was examined
      fluorimetrically. RESULTS: The following correlations were observed: (1) r =
      0.431 (P = 0.017) for activity in random urine samples and total activity in 24-h
      urines); (2) r = 0.281 (P = 0.005) for activity in random samples and activity,
      expressed as U/l, in 24-h urines. CONCLUSIONS: The data show that collection of
      urine excreted over the whole day and evaluation of total daily excretion of NAG
      seems the method of choice, at least for patients with chronic renal
      insufficiency.

PMID- 15256314
TI  - Study of glycated amino acid elimination reaction for an improved enzymatic
      glycated albumin measurement method.
AB  - BACKGROUND: In order to improve enzymatic glycated albumin measurement, we
      studied the endogenous glycated amino acid elimination reaction and the new
      bromocresolpurple (BCP) method for albumin measurement. METHODS: In the assay,
      endogenous glycated amino acids are first eliminated by oxidation by ketoamine
      oxidase. Second, glycated albumin is hydrolyzed to glycated amino acids by
      proteinase digestion, and glycated amino acids are oxidized to produce hydrogen
      peroxide, which is quantitatively measured. Third, albumin is measured by the new
      BCP method. Finally, glycated albumin value is calculated as the percentage of
      glycated albumin in total albumin. RESULTS: Glycated amino acid concentrations in
      prepared total parenteral nutrition products were increased in direct proportion
      to storage time and temperature. The glycated amino acid elimination reaction
      using ketoamine oxidase may be able to eliminate more than 15 mmol/l glycated
      amino acids. The glycated albumin values of samples calculated from the albumin
      concentrations using the new BCP method accorded with those calculated with the
      HPLC method. Fundamental performances (linearity, dilution test, analytical
      recovery, within-run and between-run CVs, interference study) of the present
      method were good. Detection of glycated albumin by the present method was
      significantly correlated with detection of glycated albumin by the high
      performance liquid chromatography method (r(p) = 0.995). CONCLUSIONS: This new
      improved method is free of interference by endogenous glycated amino acids and is
      unaffected by albumin concentration, and enables more accurate analysis of
      glycated albumin.

PMID- 15256315
TI  - Fatty acid composition of erythrocyte phospholipids is related to insulin levels,
      secretion and resistance in obese type 2 diabetics on Metformin.
AB  - BACKGROUND: Relationships between fatty acids in erythrocyte phospholipids and
      insulin parameters have been described in healthy and overweight individuals, but
      not in obese diabetics. We assessed whether erythrocyte phospholipid fatty acids
      are related to insulin parameters in obese type 2 diabetics on Metformin.
      METHODS: In 23 diabetics, the fractions of the different fatty acids in
      erythrocyte phospholipids were correlated with insulin levels, secretion,
      sensitivity, resistance and insulinemic response following a standardised
      breakfast. RESULTS: Fasting insulin levels and insulin resistance correlated
      positively with the fraction of alpha-linolenic and dihomo-gamma-linolenic acid
      and with the ratios of stearic to palmitic and dihomo-gamma-linolenic to linoleic
      acid and negatively with the fraction of palmitic acid in erythrocyte
      phospholipids. Insulin secretion correlated negatively with the fraction of
      palmitic acid. For this parameter, a positive correlation was also found with the
      sum of uneven fatty acids. Insulinemic response following a meal was negatively
      associated with the fraction of oleic acid in erythrocyte phospholipids. Insulin
      sensitivity did not correlate with erythrocyte fatty acids. CONCLUSIONS: The
      relationships found differ from those described in healthy and overweight
      individuals and may be characteristic for type 2 diabetics. They concur with the
      recommendations that saturated fat intake should be reduced and monounsaturated
      increased.

PMID- 15256316
TI  - The effect of different dialysis membranes on oxidative stress and selenium
      status.
AB  - BACKGROUND: Oxidative stress is an important risk factor for the development and
      progression of several complications in hemodialysis patients. The aim of this
      study was to evaluate the effects of two different dialysis membranes on
      oxidative stress and selenium status. METHODS: Forty long-term dialysis patients
      and 20 age-matched healthy controls were enrolled into our study. Serum
      malondialdehyde (MDA) and selenium (Se) concentrations, and glutathione
      peroxidase (GSH-Px) activities were determined before and after hemodialysis (HD)
      using a hemophan (H) or a polysulfone (PS) membrane. RESULTS: MDA levels in the
      HD patients were significantly higher than those in the control group (p <
      0.001). GSH-Px activity and selenium concentrations were significantly lower in
      HD patients compared to the control group (p < 0.001). MDA levels were
      significantly increased (p < 0.05); GSH-Px activity and selenium concentrations
      were significantly reduced (p < 0.001) in the PS membrane group compared to H
      membrane group after HD. CONCLUSIONS: Comparing with H membrane, PS membrane
      caused more oxidative stress and lower levels of Se in HD patients.

PMID- 15256317
TI  - Evaluation of some biochemical changes in diabetic patients.
AB  - OBJECTIVE: Hyperglycemia is considered a primary cause of diabetic vascular
      complications and is associated with oxidative stress, impaired trace element and
      lipid metabolism as well as pancreatic enzyme abnormalities. The role of trace
      elements in some of the metabolic dysfunctions and their contributions in the
      development of vascular complications is not clear. Therefore, the present study
      investigates the relationship among diabetes mellitus, trace elements status,
      advanced glycation end products (AGEs), advanced oxidation protein products
      (AOPP), lipid profiles, antioxidant status, nitric oxide and pancreatic amylase
      activity in the sera of 55 non-insulin-dependent diabetes mellitus (NIDDM; 35
      with microvascular complications and 20 without vascular complications), 40
      insulin-dependent diabetes mellitus (IDDM; 25 with microvascular and 15 without
      microvascular complications), and 20 nondiabetic healthy control subjects. The
      mean age of the diabetic patients was similar to that of control. The mean
      duration of the disease was 11.8 +/- 6.8 years (3-27 years) in IDDM and 7.1 +/-
      4.7 years (1-15 years) in NIDDM. METHODS: Plasma Cu, Zn, Mg, Ca, thiobarbituric
      acid-reactive substance (i.e. malondialdehyde; MDA), nitric oxide (NO),
      glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), ceruloplasmin (Cp)
      and amylase activities as well as AOPP were assessed spectrophotometrically
      whereas AGEs were estimated spectrofluorometrically in two types of diabetes
      mellitus (DM) as well as control subjects of matched sex and ages. RESULTS: SOD,
      CAT and Cp activities were decreased whereas serum alpha-amylase activity was
      increased in two types of DM in comparison to the corresponding activities of the
      control subjects. The plasma levels of MDA, NO and Cu were increased but GSH, Zn,
      Mg and Ca levels were significantly diminished in diabetic patients as compared
      to the controls. The averages of total cholesterol (CHOL), triglyceride (TG) and
      low-density lipoprotein-cholesterol (LDLc) were higher in both types of diabetes
      mellitus in comparison to the control subjects. The mean value of high-density
      lipoprotein-cholesterol (HDLc) was lower in both types of diabetes mellitus.
      Further, the mean values of AGEs and AOPP were elevated in diabetic patients vs.
      control. These parameters are significantly higher in NIDDM patients when
      compared to the IDDM subjects. Slight but not significant differences in these
      parameters were observed in patients with diabetic complications when compared to
      that of without diabetic complications. CONCLUSION: These findings may explain
      the role of impaired trace element status, defect of antioxidants and increased
      of AGE and AOPP in the pathogenesis of pancreas and the vascular complications of
      diabetes mellitus. Oxidative stress is increased in both types of DM, but it is
      more in NIDDM patients than in IDDM subjects. In addition, oxidative stress also
      plays an important role in the formation of AGEs and AOPP in DM.

PMID- 15256318
TI  - Identification of a specific marker for hepatitis C virus infection using
      capillary zone electrophoresis.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is now becoming a common health
      problem in both developed and developing countries. The limitation of the
      available diagnostic approaches enhances the efforts to have a rapid, sensitive,
      and specific diagnostic testing for HCV infection. Capillary zone electrophoresis
      (CZE) is a fully automated analytical technique whose popularity is quickly
      increasing in the clinical chemistry laboratory. CZE can analyze nanoliters or
      less of samples with detection sensitivity at the attomole level (10(-18) mol) or
      less. METHODS: CZE was optimized for the identification of a specific marker of
      HCV infection. The performance characteristics of the CZE for the detection of
      HCV RNA peak were evaluated in comparison with standard nested PCR. RESULTS: A
      characteristic peak at 2.72 min was identified only in the CZE electropherogram
      of urine samples from HCV-infected individuals. The nature of the characteristic
      peak was investigated and confirmed to be HCV RNA using PCR and other biochemical
      treatments including RNase, DNase, and trypsin enzymes. CZE showed high degrees
      of sensitivity (94%) and specificity (96%) in comparison with the nested PCR.
      CONCLUSION: CZE provides a rapid, inexpensive, sensitive, and specific analytical
      method for diagnosis and mass screening of a large number of HCV-infected
      individuals.

PMID- 15256319
TI  - Rapid simultaneous quantification of immunosuppressants in transplant patients by
      turbulent flow chromatography combined with tandem mass spectrometry.
AB  - BACKGROUND: Immunosuppressant therapeutic drug monitoring (TDM) is an important
      requirement in the management of post-transplant patients. Our aim was to develop
      and evaluate a robust high-throughput method using turbulent flow chromatography
      (TFC) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for
      the simultaneous quantification of cyclosporin A (CsA), tacrolimus (FK 506) and
      sirolimus. METHODS: A total of 1483 EDTA-blood pre-dosage samples from 147
      kidney, 67 liver, 15 kidney/pancreas, and 48 bone marrow recipients were
      collected. After hemolysis and protein precipitation of 50 microl blood, fast and
      efficient on-line matrix elimination was achieved using turbulent flow
      chromatography. Tandem mass spectrometric detection and quantification was
      performed using multiple reaction monitoring (MRM). RESULTS: The total analysis
      time of the column switching method was 3 min. The method was linear from 4.5 to
      1500 ng/ml for cyclosporin A, from 0.2 to 100 ng/ml for tacrolimus, and from 0.4
      to 100 ng/ml for sirolimus. The accuracy was >95%. Within and between-run assay
      variation coefficients ranged from 2.4% to 9.3%. Excellent correlation with other
      standard methods (immunoassay, HPLC) was observed. CONCLUSIONS: The presented
      turbulent flow chromatography-tandem mass spectrometric platform offers a very
      fast, simple and economical method with an excellent validation profile and is
      well suited for daily pre- and post-dosage immunosuppressant monitoring.

PMID- 15256320
TI  - Role of concurrent S. mansoni infection in H. pylori-associated gastritis: a flow
      cytometric DNA-analysis and oxyradicals correlations.
AB  - BACKGROUND/AIM: Helicobacter pylori infection is associated with the development
      of atrophic gastritis and increased gastric epithelial proliferation that is
      important in developing gastric carcinoma. Some countries with a high prevalence
      of H. pylori infection have high gastric cancer rates, whereas in others these
      rates are low. Several theories have been advanced to explain this phenomenon.
      One of these explanations is that the concurrent parasitic infection that is
      common in the African population might alter the immune response to H. pylori
      infection and reduce the incidence of atrophic gastritis. The aim of the present
      study was to assess whether concurrent Schistosoma mansoni infection with H.
      pylori has an effect on gastric mucosal injury in view of cell proliferation,
      apoptosis, pathological changes, nitric oxide (NO), oxyradicals and antioxidant
      capacity status. PATIENTS/METHODS: Between April 2001 and March 2002, 73 patients
      were subjected to upper gastrointestinal endoscopy for dyspepsia and liver
      cirrhosis in the National Liver Institute, Menoufiya University. Biopsies were
      obtained from any lesion as well as from apparently healthy mucosa. Specimens
      were preserved in RNA later solution, and then kept at -80 degrees C until
      utilized for estimation of DNA-flow cytometric assay, reduced glutathione (GSH),
      catalase (CAT), superoxide dismutase (SOD), NO and lipid peroxidation (LPO)
      product--malondialdehyde (MDA). Diagnosis of bilharziasis was done by stool
      analysis, or by sigmoidoscopy and rectal snip. RESULTS: Of the 73 patients, 48
      were H. pylori-positive, 34 of them were positive and 14 were negative for S.
      mansoni. Of the 25 H. pylori-negative cases, 18 were positive and 7 were negative
      for S. mansoni. Concurrent infection with S. mansoni occurred in 34 patients and
      they had reduced DNA S-phase (7.57 +/- 4.99 vs. 14.5 +/- 3.11, P = 0.001),
      reduced proliferation activity (9.95 +/- 3.95 vs. 16.78, P < 0.004) and reduced
      apoptosis (21.83 +/- 11.64 vs. 26.0 +/- 8.31, P > 0.05) compared with H. pylori
      infected patients alone. CONCLUSIONS: The results demonstrate that concurrent
      helminthes infection may modify the inflammatory response to gastric H. pylori
      infection manifested by the reduction of oxyradical-induced DNA-damage, apoptosis
      and cellular proliferation activity, and the increase in antioxidant production.
      Concurrent S. mansoni infection may have a protective effect against the possible
      progression of H. pylori-induced gastritis towards gastric carcinoma.

PMID- 15256321
TI  - High-performance liquid chromatographic detection of lipid peroxidation in human
      seminal plasma and its application to male infertility.
AB  - BACKGROUND: A simple and reliable high-performance liquid chromatographic (HPLC)
      method has been developed and validated for the analysis of malondialdehyde (MDA)
      in human seminal plasma. METHODS: After human seminal plasma is hydrolyzed, MDA
      is reacted with thiobarbituric acid (TBA) to form MDA(TBA)(2), a red-colored
      adduct with maximum absorbance at 532 nm. HPLC separation of the adduct in human
      seminal plasma was performed on a Lichrospher C(18) column. RESULTS: A mobile
      phase composed of 0.025 mol/l KH(2)PO(4) (pH 6.2)--methanol in the ratio 58:42
      (v/v) was found to be the most suitable for this separation. Under the
      chromatographic conditions described, the MDA-TBA adduct had a retention time of
      approximately 4 min and good separation and detectability of MDA in human seminal
      plasma sample was obtained. The method proved to be linear calibration in the
      range of MDA from 0.10 to 2.50 micromol/l. The relative standard deviations of
      within- and between-assay for MDA analysis were 3.1% and 3.8%, respectively. The
      average recovery was 90.0-98.8% for the human seminal plasma samples. The method
      has been successfully applied to the study of the lipid peroxidation levels in
      the seminal plasma of male infertility. Semen samples were obtained from healthy
      volunteers and infertile males. Ejaculates were classified into studied subgroups
      and defined as: obstructive azoospermia, non-obstructive azoospermia,
      oligozoospermia, asthenozoospermia, oligoasthenozoospermia and
      oligoasthenoteratozoospermia. With the exception of obstructive azoospermic
      group, MDA concentrations of seminal plasma in control group had very significant
      difference with those in other infertile groups (P < 0.01). CONCLUSIONS: This
      indicated that lipid peroxidation could be harmful to male sperm and reproductive
      system, which may lead to male infertility.

PMID- 15256322
TI  - Free radical toxicity and antioxidants in Guillain-Barre syndrome, a preliminary
      study.
AB  - BACKGROUND: The generation of reactive oxygen species (ROS) has been implicated
      in the pathogenesis of a vast array of disease processes including some
      neurological disorders. METHOD: Ten patients with Guillain-Barre syndrome (GBS)
      and 10 age and sex-matched controls were included in this study. The erythrocyte
      glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) levels,
      as well as plasma antioxidant vitamins C and E and serum glutathione-S
      transferase (GST) levels were estimated spectrophotometrically. RESULTS: The
      plasma vitamin E and the serum total glutathione-S-transferase levels were
      markedly increased in both pre- and post-treated cases of GBS when compared to
      controls. The erythrocyte glutathione and malondialdehyde levels were
      significantly reduced in GBS cases when compared to normals. However, plasma
      vitamin C and erythrocyte superoxide dismutase were not altered when compared to
      controls. CONCLUSION: Free radical toxicity may have an influence in patients
      suffering from GBS.

PMID- 15256323
TI  - Evaluation of a point-of-care assay for cardiac markers for patients suspected of
      acute myocardial infarction.
AB  - BACKGROUND: Creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) are
      important biomarkers for the diagnosis and rule-out of acute myocardial
      infarction (AMI) of patients who presented to the emergency department (ED) with
      chest pain. With new rapid ED assessment protocols, there is increasing pressure
      to produce results with a short turnaround time (TAT), and point-of-care (POC)
      testing is one alternative for providing fast results. METHODS: In a multicenter
      study, we evaluated the analytical precision, sensitivity and specificity of the
      RAMP (Response Biomedical) CK-MB and cTnI POC assays and compared results against
      the Triage (Biosite) POC and the Dimension RxL (Dade Behring) central-laboratory
      assays on 365 subjects, including 185 patients suspected of AMI, and determined
      the normal range on 180 healthy individuals. At one site, the clinical
      sensitivity and specificity were estimated in 121 patients and healthy subjects
      with AMI using the European Society of Cardiology (ESC)/American College of
      Cardiology (ACC) definition of AMI. Results from healthy individuals and those
      with ST elevation and non-ST elevation AMI were included in a receiver operating
      characteristic (ROC) curve analysis. RESULTS: Intra- and total imprecision ranged
      from 7.2% to 11.4% for cTnI at 0.22, 1 and 5 ng/ml and 4.8% to 8.6% for CK-MB at
      7, 14 and 25 ng/ml. The upper limit of linearity was 32 ng/ml with an average
      recovery of 105% for cTnI and 80 ng/ml with a 106% recovery for CK-MB. The lower
      limit of detection was 0.03 ng/ml (10% coefficient of variance [CV] = 0.21 ng/ml)
      for cTnI and 0.32 ng/ml for CK-MB. The upper reference limit (normal range) was <
      0.03 ng/ml for cTnI and 0-3.7 ng/ml for CK-MB. Analytical correlation against
      Dimension RxL were RAMP=(0.456 x RxL) + 0.11 (r = 0.988, n = 364) for cTnI and
      RAMP=(0.966 x RxL) + 0.60 (r = 0.986, n = 363) for CK-MB and against Triage,
      RAMP=(0.626 x Triage) + 0.164 (r = 0.969, n = 364) for cTnI and RAMP=(0.845 x
      RxL) - 0.495 (r = 0.952, n = 363) for CK-MB. On 39 AMI and 67 non-AMI patients,
      the clinical sensitivity, specificity and diagnostic efficiency of the cTnI and
      CK-MB RAMP assays were not significantly different from predicate assays.
      CONCLUSIONS: The RAMP cardiac marker assays are alternatives to other FDA-cleared
      central laboratory and POC testing devices.

PMID- 15256324
TI  - Analytical performance of a kinetic method for the determination of lactate
      dehydrogenase catalytic concentration in cerebrospinal fluid.

PMID- 15256325
TI  - Prevalence of acanthosis nigricans in newly-diagnosed type 2 diabetes.
AB  - OBJECTIVE: To determine the prevalence of acanthosis nigricans in a population of
      patients with newly-diagnosed type 2 diabetes mellitus. METHODS: Chart review of
      men and women treated for newly diagnosed type 2 diabetes at the University
      Diabetes Treatment Center at Parkland Health and Hospital System in Dallas, Texas
      between January 1998 and December 1999. The presence of acanthosis nigricans was
      evaluated on the posterior neck of each individual. RESULTS: Of 216 patients
      identified with newly diagnosed type 2 diabetes, 78 individuals (36.1%) presented
      with acanthosis nigricans involving the back of the neck. Most subjects were
      obese, with the mean BMI of the subject population at 32.7 +/- 5.8 kg/m2 (mean +/
      SD). Prevalence of acanthosis nigricans increased with degree of obesity, with
      fully 54.1% of the population with a BMI of > or = 30 kg/m2 manifesting the skin
      lesion. The prevalence of acanthosis nigricans differed notably among ethnic
      groups, as the lesion occurred in 50 (52.6%) of 95 African-American subjects and
      28 (35.9%) of 78 Latin-American subjects. Patients with acanthosis nigricans
      required markedly higher insulin doses (82.3 +/- 7.2 units/day) to achieve
      euglycemia compared to those without the disorder (50.2 +/- 5.7 units/day).
      CONCLUSION: These results suggest that acanthosis nigricans is a readily visible
      marker of hyperinsulinemia and is frequently encountered in patients with type 2
      diabetes. Prevalence of acanthosis nigricans is influenced by ethnicity and BMI
      in this patient population.

PMID- 15256326
TI  - Dependency and analgesia related to treatment with subcutaneous octreotide in
      patients with growth hormone-secreting tumors.
AB  - OBJECTIVE: To describe three patients diagnosed with somatotropinomas in whom the
      analgesic effect of octreotide was observed, along with dependency to the drug.
      METHODS: These patients had pituitary macroadenomas treated with transphenoidal
      surgery and pituitary radiotherapy, and received high daily doses (>900
      microg/day) of subcutaneous octreotide because of persistent high levels of
      growth hormone and insulin-like growth factor I (IGF-I). RESULTS: Headache
      occurred prior to drug administration in all three cases, with relief soon after.
      We also observed tolerance to octreotide's analgesic and anti-secretory actions
      (one patient), craving for the drug (two patients), withdrawal syndrome (one
      patient), and drug abuse (one patient). CONCLUSION: Dependency syndrome may occur
      when high doses of octreotide are used, sometimes leading to drug abuse.
      Tolerance to the growth hormone anti-secretory effect of the drug may encourage
      physicians to increase doses to levels at which drug dependency has been
      observed. Sustained release somatostatin analogs may represent a solution to this
      problem.

PMID- 15256327
TI  - Improved perioperative glycemic control by continuous insulin infusion under
      supervision of an endocrinologist does not increase costs in patients with
      diabetes.
AB  - OBJECTIVE: To evaluate whether glycemic control can be improved perioperatively
      by implementing an insulin infusion protocol for patients with diabetes
      undergoing coronary artery bypass graft (CABG) surgery, without creating an
      additional financial burden. We also evaluated impact of such a protocol on
      hospital length of stay (LOS) and development of deep sternal wound infections
      (DSWI). METHODS: We developed an insulin infusion glycemic control protocol
      (IGCP) under supervision and consultation of an endocrinologist. Outcomes of CABG
      surgery patients with diabetes receiving our IGCP (year 2000) were compared to
      those of a conventional group of patients with diabetes undergoing CABG prior to
      the use of the IGCP (year 1999). Cost analysis was performed on data from the
      hospital's cost accounting database, which included additional costs related to
      the IGCP. RESULTS: The IGCP group (n=107) showed significantly better glycemic
      control (mean blood glucose level 183.5 mg/dl +/- SD 53.2 mg/dL; P<0.0001) than
      the conventional group (n = 81; mean blood glucose level 241.67 mg/dL +/- 75.93
      mg/dL). Overall hospital costs were not significantly affected by the
      intervention. The IGCP group showed a trend toward shorter LOS (IGCP 6.34 days;
      conventional group 6.58 days) and a reduced rate of DSWI (IGCP 4.63%;
      conventional group 4.94%). CONCLUSIONS: Glycemic control can be improved by
      implementation of IGCP with no significant additional health care costs.
      Endocrinologist involvement did not increase costs and improved glycemic
      management of CABG patients with diabetes.

PMID- 15256328
TI  - Ectopic Cushing's syndrome caused by an esthesioneuroblastoma.
AB  - OBJECTIVE: To report a case of florid Cushing's hormone (ACTH) secretion related
      to the presence of an esthesioneuroblastoma (ENB). METHODS: We present clinical,
      laboratory, and pathologic findings in a 36-year-old Caucasian man presenting
      with Cushing's syndrome. Results of computed tomography (CT), magnetic resonance
      imaging (MRI), positron emission tomography (PET) scanning, and somatostatin
      receptor scintigraphy are presented, along with tumor pathology findings.
      RESULTS: After initial biochemical studies suggestive of ectopic Cushing's
      syndrome, CT of the chest and abdomen revealed multiple cavitated pulmonary
      lesions, an ischiorectal mass, and bilateral adrenal hyperplasia. MRI of the
      pituitary gland revealed normal findings. Both PET scanning with [18 F]
      flurodeoxyglucose (FDG) and somatostatin receptor scintigraphy with 111 indium
      penetetreotide (Octreoscan) revealed strong tracer uptake in the ethmoid region.
      CT and MRI of the sinuses and brain subsequently localized a 5-cm mass in the
      ethmoid sinuses with intracranial extension. On biopsy, pathology results were
      consistent with a diagnosis of ENB, and immunohistochemical analysis revealed
      that tumor cells were strongly positive for ACTH, synaptophysin, and S-100,
      providing definitive diagnosis of ACTH-producing ENB. Hypercortisolemia was
      initially controlled by metyrapone, then by external beam radiation therapy (RT).
      CONCLUSION: This case illustrates the usefulness of nuclear imaging in the
      diagnosis of ENB, and the importance of prompt control of hypercortisolemia in
      Cushing's syndrome.

PMID- 15256330
TI  - Hemorrhagic Rathke's cleft cyst presenting as diplopia.
AB  - OBJECTIVE: To report a case of uncommon presentation of hemorrhagic Rathke's
      cleft cyst (RCC) extending into the cavernous sinus, causing diplopia. METHOD: We
      present clinical, radiologic, and histologic findings on this patient, and review
      related medical literature. RESULTS: A 34-year-old man presented with a 4-month
      duration of worsening left-sided headache with acute development of diplopia
      which worsened upon looking to the left. Magnetic resonance imaging identified a
      left pituitary mass with posterior extension and involvement of the cavernous
      sinus. Hormone level evaluation revealed a low free thyroxine index and elevated
      prolactin levels, and normal levels of thyroid stimulating hormone, growth
      hormone, insulin-like growth factor type 1, and cortisol. The patient underwent
      transsphenoidal resection of a yellow fibrous mass from the left side of the
      sella. Tumor tissue pathology was consistent with a RCC that may have undergone
      secondary hemorrhage and rupture. Postoperatively, this patient developed
      transient diabetes insipidus, and required levothyroxine therapy for
      hypothyroidism. The diplopia improved, though he continues to complain of
      episodic headaches. CONCLUSION: RCCs are challenging to diagnose, as they can
      cause symptoms related to enlargement and hemorrhage. Imaging studies and other
      diagnostic measures may, therefore, describe heterogeneous features. The most
      common clinical presentation of this disorder is a manifestation of pituitary
      dysfunction, such as hyperprolactinemia, diabetes insipidus, and, occasionally,
      apoplexy. These symptoms may be accompanied by headache. Visual disturbances
      often appear, usually as visual field defects and decreased visual acuity. This
      case demonstrates that nonpituitary masses such as RCC can hemorrhage and extend
      into the cavernous sinus, causing acute ophthalmoplegia.

PMID- 15256329
TI  - Recurrent hypercalcemia due to ectopic production of parathyroid hormone-related
      protein and intact parathyroid hormone in a single patient with multiple
      malignancies.
AB  - OBJECTIVE: To report a case of recurrent hypercalcemia due to ectopic production
      of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP)
      from transitional cell carcinoma of the urinary bladder. METHODS: We present
      clinical, laboratory, and pathologic findings in a 73-year-old man with recurrent
      hypercalcemia. Results of serum calcium, PTH, PTH-rP and immunostaining of tumors
      for PTH and PTH-rP over 9 years are presented. RESULTS: In 1990 this patient was
      diagnosed with primary hyperparathyroidism, which was cured by resection of a
      parathyroid adenoma in the neck. Hypercalcemia recurred in 1992, and he was found
      to have squamous cell carcinoma of the right lung. PTH-rP levels were not
      measured, but the resected tumor immunostained positive for the presence of PTH
      rP. The patient subsequently remained normocalcemic until 1996, when the plasma
      calcium and PTH levels increased again. Surgical exploration of the neck revealed
      no parathyroid adenoma. Elevated plasma levels of calcium and PTH persisted after
      surgery. In 1998 the patient was diagnosed with stage IV invasive transitional
      cell carcinoma (TCC) of the urinary bladder and underwent radical cystectomy. The
      tumor tissue was not immunoreactive to PTH-rP. A year later, plasma levels of PTH
      and PTH-rP increased, but surgical re-exploration of the neck again revealed no
      parathyroid adenoma. CT scanning identified a large retroperitoneal mass, and a
      CT-guided biopsy of the mass showed metastatic, poorly differentiated TCC
      immunopositive for PTH and PTH-rP. CONCLUSION: This is the first report of
      ectopic production of PTH from metastatic TCC of the urinary bladder coexisting
      with PTH-rP mediated hypercalcemia.

PMID- 15256331
TI  - Pituitary apoplexy precipitating diabetes insipidus.
AB  - OBJECTIVE: To describe a case of pituitary apoplexy complicated by diabetes
      insipidus and to review management of patients with pituitary apoplexy and water
      excretion disturbances associated with transsphenoidal surgery. METHODS: We
      describe clinical, laboratory, and radiologic findings in a patient with
      pituitary apoplexy and central diabetes insipidus. RESULTS: A 74-year-old woman
      presented with severe headache and sudden loss of vision for 12 hours,
      accompanied by thirst and frequent urination. Visual field examination
      demonstrated bitemporal hemianopsia. Her laboratory findings were significant for
      a serum sodium level of 152 mEq/L and urine specific gravity of <1.005. A
      magnetic resonance imaging scan of her pituitary gland identified a 3.5-cm
      suprasellar mass compressing the optic chiasm. She subsequently underwent
      transsphenoidal pituitary surgery with subtotal resection of this mass.
      Microscopic evaluation of tumor tissue revealed a pituitary adenoma with evidence
      of recent infarct and hemorrhage. Her clinical and biochemical course was
      consistent with the triphasic response that may occur after pituitary surgery
      related to damage to the hypothalamus and supraopticohypophyseal tract.
      CONCLUSION: Pituitary apoplexy may be rarely associated with diabetes insipidus.

PMID- 15256333
TI  - Catecholamine excess in pheochromocytoma inducing insulin resistance.

PMID- 15256332
TI  - Clinical use of teriparatide in the real world: initial insights.
AB  - OBJECTIVE: To summarize expert opinion regarding clinical application of the
      recently introduced anabolic agent teriparatide [human parathyroid hormone (1
      34)] in treatment of postmenopausal osteoporosis in women, and osteoporosis in
      men. SUMMARY: The anabolic agent teriparatide was approved for clinical use by
      the Food and Drug Administration (FDA) on November 26, 2002. Since the launch of
      teriparatide, many more questions about clinical use of this exciting agent have
      emerged than there are answers provided by clinical trials or FDA-approved
      product labeling. A group of physicians with a broad range of experience in
      research and clinical applications of teriparatide met recently to address
      practical issues related to its use. This manuscript is a compendium of the
      consensus opinions of the authors that attempts to provide practical answers to
      many real-world questions being asked about teriparatide therapy since its
      approval by the FDA.

PMID- 15256334
TI  - Practical office strategies for weight management of the obese diabetic
      individual.
AB  - SUMMARY: Obesity is a key component of the insulin-resistance syndrome of type 2
      diabetes, and intensifies comorbidities underlying the increased cardiovascular
      risk of individuals with type 2 diabetes. Weight loss leads to dramatic
      beneficial effects, with reductions in blood glucose levels and improvements in
      lipid profiles and blood pressure that often necessitate reductions in
      medications. Successful long-term weight loss is difficult to achieve in patients
      with diabetes, as standard dietary approaches often have minimal long-term
      impact, and intensive management strategies designed to improve glycemic control
      often contribute to further weight gain in these patients. This article offers a
      review of newer strategies for enhancing lifestyle change and weight loss in the
      obese diabetic individual. Use of meal replacements provides structure with
      portion control, and increased intake of fruits and vegetables promotes a
      healthier eating style for these patients. Encouraging physical activity such as
      walking, stair climbing, and gardening can significantly improve
      cardiorespiratory fitness and glycemic control, and helps patients maintain
      weight loss. Self-monitoring through lifestyle diaries can reinforce the healthy
      behaviors necessary for long-term management of obesity. Adjunctive antiobesity
      medication, medically-supervised intensive weight loss programs, and minimally
      invasive gastric bypass procedures are important options for patients unable to
      make significant progress with behavioral changes.

PMID- 15256335
TI  - More good economic news.

PMID- 15256336
TI  - Scat! Scat.

PMID- 15256337
TI  - A caution regarding U-500 insulin by continuous subcutaneous infusion.

PMID- 15256338
TI  - Visual vignette. Diabetic muscle infarction.

PMID- 15256339
TI  - Visual vignette. Recurrence of thyroid cancer with penetration into the skin.

PMID- 15256341
TI  - Overlapping and interactive pathways regulating appetite and craving.
AB  - Multidisciplinary research in recent years has delineated the hypothalamic
      hardcore wiring that encodes appetitive drive. The appetite regulating network
      (ARN) consisting of distinct orexigenic and anorexigenic circuitries operates in
      the arcuate nucleus-paraventricular nucleus axis of the hypothalamus to propagate
      and relay the appetitive drive, and is subject to modulation by excitatory and
      inhibitory messages from the lateral hypothalamus and ventromedial nucleus,
      respectively. Reciprocal afferent humoral signals, comprised of anorexigenic
      leptin from white adipose tissue and orexigenic ghrelin from stomach, to the ARN
      integrate the moment-to-moment regulation of energy homeostasis. Various loci in
      the ARN and afferent hormonal feedback circuitry in the rodent brain are
      important for food craving elicited by drugs of abuse. This convergence of
      neurochemical and hormonal signaling has now paved the way to address the
      fundamental question of whether cellular and molecular events that underlie the
      appetitive drive in response to diminished energy stores in the body are akin to
      drug craving during withdrawal in humans.

PMID- 15256342
TI  - Interaction of satiety and reward response to food stimulation.
AB  - Obesity is among the most pressing health issues affecting developed countries.
      The etiology of obesity remains unclear despite its associated health risks. We
      propose a framework for obesity modeled upon overeating as a substance dependence
      disorder arising from a combination of abnormal cognitive and neuroendocrine
      processes. While significant work in both of these fields has investigated the
      body's regulation of satiety signals, fewer studies have focused upon the
      mechanisms by which these two seemingly disparate systems interact. Although
      emotional states have been shown to mediate reward processing, the implications
      for hunger mediating reward have not previously been addressed. We review the
      interaction between central satiety signals and reward responses to food stimuli
      and discuss the implications of this research for understanding the causes of
      obesity.

PMID- 15256343
TI  - Similarity between obesity and drug addiction as assessed by neurofunctional
      imaging: a concept review.
AB  - Overeating in obese individuals shares similarities with the loss of control and
      compulsive drug taking behavior observed in drug-addicted subjects. The mechanism
      of these behaviors is not well understood. Our prior studies with positron
      emission tomography (PET) in drug-addicted subjects documented reductions in
      striatal dopamine (DA) D2 receptors. In pathologically obese subjects, we found
      reductions in striatal DA D2 receptors similar to that in drug-addicted subjects.
      Moreover, DA D2 receptor levels were found to have an inverse relationship to the
      body mass index of the obese subjects. We postulated that decreased levels of DA
      D2 receptors predisposed subjects to search for reinforcers; in the case of drug
      addicted subjects for the drug and in the case of the obese subjects for food as
      a means to temporarily compensate for a decreased sensitivity of DA D2 regulated
      reward circuits. Understanding the mechanism in food intake will help to suggest
      strategies for the treatment of obesity.

PMID- 15256344
TI  - Adolescent drug addiction treatment and weight gain.
AB  - Neurotransmitter release in the nucleus accumbens use has been linked to self
      administration and learning following drug use. This endogenous reward system is
      also activated following food intake or sex. Therefore, rebound hyperphagia
      following abstinence may be a mechanism to replenish the release of
      neurotransmitters in this reward system, leading to increased weight gain and a
      rise in body mass index during recovery from substance abuse. In this report, we
      examined the relationship between supervised drug abstinence and increased weight
      gain among adolescents at a residential substance abuse treatment center. Mean
      weight change over time was followed by repeated analysis of weight and body mass
      index. Significant weight gain and body mass index increase was observed during
      supervised and confirmed abstinence from drug use. Furthermore, significant
      interactions between tobacco use and primary substance use disorder with weight
      gain was demonstrated by multivariate analysis of variance.

PMID- 15256345
TI  - Examining problem drinking and eating disorders from a gendered perspective.
AB  - The two studies presented here examined the relationship between problem drinking
      and eating disorders in college students. Although there was little evidence of a
      concurrent relationship between the two, there were differences related to
      gender. In addition, there were differences between women who were and were not
      sorority members with respect to problem drinking, but not eating disorders. The
      value of addressing these problems from a gendered perspective is discussed.

PMID- 15256346
TI  - Genes and/or jeans?: Genetic and socio-cultural contributions to risk for eating
      disorders.
AB  - Eating disorders are prevalent among young adult females and pose serious
      psychological and medical risks. Notwithstanding important advances, efforts to
      develop effective means of preventing and treating eating disorders have been
      limited by an incomplete understanding of their multifactorial etiology. Whereas
      epidemiologic data strongly suggest the influence of socio-cultural context in
      moderating risk, many hypotheses about how these effects are exerted have
      remained empirically unevaluated. Specifically, experimental and observational
      data suggest that social transition (e.g., transnational migration, urbanization,
      modernization), Western media exposure, and certain peer environments (involving
      social comparison and teasing) may all contribute to risk. With respect to
      genetic influences on etiology, family and twin studies have supported a genetic
      diathesis to eating disorders. Whereas, molecular genetic studies have generated
      interesting leads- with the most promising findings emerging for genes related to
      the function of serotonin-they have yet to identify well-replicated
      susceptibility loci. This paper reviews the data supporting both socio-cultural
      and genetic contributions for eating disorders and suggests productive future
      strategies for continuing to unravel their likely multiple and complex
      interactions.

PMID- 15256347
TI  - Body mass index and alcohol use.
AB  - BACKGROUND: Obesity, inactivity and being overweight are leading causes of
      morbidity and mortality in the United States. The relationship between eating,
      overeating, and addiction have been discussed, debated and more recently
      investigated. We have hypothesized that drugs of abuse compete with food for
      brain reward sites. Overeating and obesity may act as protective factors reducing
      drug reward and addiction. METHODS: In the first part of this study, 374 charts
      of all active weight management patients in a 12-month period were examined.
      Demographic information, laboratory testing, psychiatric diagnostic interview,
      alcohol and drug history were reviewed. A detailed alcohol use, abuse, dependence
      history was present in 298 charts as part of the pre-bariatric evaluation. The
      relationship between BMI and alcohol use among female patients (n = 298) was then
      analyzed. RESULTS: We found a significant (p <.05) inverse relationship between
      BMI and alcohol consumption. The more obese the patient was, the less alcohol
      they consumed. The percentage of women who consumed alcohol in the past year
      decreased as BMI level increased. These results confirmed our surgeons'
      perception that it is rare to find a morbidly obese patient excluded for
      bariatric surgery because of excessive alcohol consumption. CONCLUSIONS: Obese
      patients have lower rates of alcohol use than found in the general population of
      women. As BMI increases, lower rates of alcohol consumption are found. Overeating
      may compete with alcohol for brain reward sites, making alcohol ingestion less
      reinforcing.

PMID- 15256348
TI  - African American women: a life course of care?
AB  - Twenty-five years of research on family care to dependent elders has produced a
      theoretically sophisticated understanding of the process of family caregiving.
      Although caregiving models initially were developed and tested on predominantly
      White samples, more recent work has applied these models to African American
      caregivers. This investigation builds on the comparative perspective by
      describing elder care in African American families through the eyes of the
      culture in which it occurs. Thirty-two African American caregivers were
      interviewed and asked to discuss their caregiving careers from a life course
      perspective. Qualitative narratives described three pathways to care: elder care
      only, limited life course of care, and live course of care. Recognition of the
      various pathways to care will enlighten tailored interventions.

PMID- 15256349
TI  - Barriers to childhood immunization: findings from a needs assessment study.
AB  - This study examines the current status of immunization among 0-3 year old
      children in Bakersfield and identifies barriers that prevent families from
      immunizing their children. A survey research design using a stratified sampling
      method was employed to collect data from 207 randomly selected English and
      Spanish speaking households having at least one child between the ages of 0-3 in
      Bakersfield. The findings reveal that 49% of the parents had no shot cards
      regarding children's immunization status. However, a significant majority of them
      immunized their children despite having no records. The most commonly reported
      consumer related barrier for late immunization was having a sick child followed
      by lack of parental memory and fear of side effects. The major provider-related
      barriers included lack of an opening for an appointment with the health care
      provider, limited clinic hours, and long lines in clinics. Lack of transportation
      was the single most systemic barrier. These findings suggest that reminder calls,
      increased transportation, weekend clinics and better rapport with parents can
      improve the immunization rates in ethnically diverse rural communities.

PMID- 15256350
TI  - Physicians as medical center "extenders" in end-of-life care: physician home
      visits as the lynch pin in creating an end-of-life care system.
AB  - The article reviews a successful community-based end-of-life home care program.
      Specifically, physician visits were compared in the models of care studied, and
      it was concluded that the community-based model patients benefited significantly
      over the standard model of care patients due to the use of physicians.

PMID- 15256351
TI  - Medicaid 1915(c) home and community-based services waivers: a national survey of
      eligibility criteria, caps, and waiting lists.
AB  - With 43 states reporting budget deficits in 2002, there is increasing interest in
      the cost controls methods that state governments use on the 229 Medicaid home and
      community-based services (HCBS) waiver programs which, in 2001, provided services
      to more than 830,000 persons and cost more than $14.2 billion. This paper reports
      findings from a national survey of all waiver programs regarding cost containment
      strategies used in 2002. Responses from 76 percent of all waivers show that 57
      percent used some type of financial cap, 33 percent used more restrictive
      financial eligibility criteria than for institutional services, and the vast
      majority of states limited the number of waiver slots available. Overall, the
      waiver programs reported that 157,640 persons were on waiting lists in 2002.
      These findings provide an important basis for comparison between states because
      the use of these strategies may restrict individuals' choice of services and
      result in unnecessary institutionalization.

PMID- 15256352
TI  - What makes women feel powerful? An exploratory study of relationship power and
      sexual decision-making with African Americans at risk for HIV/STDs.
AB  - Because of the importance of relationship power and cultural norms on women's
      ability to protect themselves from HIV/STDs, effective interventions must address
      power differentials among men and women. These programs need to be informed by
      and adapted to the cultural values of the target population. Accordingly, we
      conducted exploratory interviews with 22 young African American women at risk of
      HIV/ STDs and unintended pregnancy and their male partners regarding the meaning
      of power in heterosexual relationships, what makes a woman feel powerful in a
      relationship with a man, and who makes sexual and reproductive decisions in their
      relationships. Content analyses suggested that relationship power was linked to
      control and decision-making for most participants; yet, others appeared to
      associate power with positive relationship qualities such as respect and
      security. In addition, most participants reported that they shared decision
      making about sexual and reproductive matters with their partners. Subsequently,
      interviews were conducted with another 40 women to explore and identify cultural
      beliefs regarding what makes women feel powerful in their relationships with
      their husbands or partners. Cultural consensus analysis was performed and results
      indicated that the participants comprise a cultural group with shared beliefs
      about what makes women feel powerful in their relationships. Participants
      believed that women's sense of power in their relationships came from (1) knowing
      what they want and having autonomy and control; (2) the quality of their
      relationships; (3) having resources to provide for their families; and (4)
      physical attractiveness and sexual factors.

PMID- 15256353
TI  - Factors related to postpartum depressive symptoms in low-income women.
AB  - OBJECTIVE: This study examined the relationship of depressive symptoms to
      psychosocial and lifestyle variables in postpartum women. DESIGN: The Mothers'
      Overweight Management Study (MOMS) was a randomized, weight-gain prevention
      trial. Baseline data are presented on the Beck Depression Inventory (BDI),
      Perceived Stress Scale, Social Support Questionnaire, smoking status, body
      weight, waist circumference, and step counts. SUBJECTS/SETTING: The study was
      conducted at the Special Supplemental Feeding Program for Women, Infants, and
      Children (WIC). Women (N = 151) had to be over the age of 18 years and have a
      child under two years of age to participate. RESULTS: Fifty-one percent of the
      women (mean age = 27 years; mean of 30 weeks postpartum) reported depressive
      symptoms (27% mild, 21% moderate, and 3% severe). Overall, stress scores were
      high (Mean = 27.2) and activity levels low (Mean steps = 5984). Mean body mass
      index was 30.2. Neither body weight nor steps walked were related to depressive
      symptoms in the bivariate or regression analyses. However, stress and social
      support were related to symptoms. Women without symptoms reported significantly
      less stress than the mild and moderate/ severe symptom groups (Means = 23.4,
      29.6, and 32.7, respectively, p <.001). Mean social support satisfaction was
      significantly higher for non-depressed women compared to women in the
      moderate/severe symptom range (Means = 5.9 and 4.7 respectively, p <.001). Stress
      and current smoking status explained 46% of the variance in depressive symptoms.
      CONCLUSIONS: These data emphasize the need for stress management and other tools
      such as increasing activity levels to prevent or lessen depressive symptoms.

PMID- 15256354
TI  - Stress, quality of life and physical activity in women with varying degrees of
      premenstrual symptomatology.
AB  - Premenstrual symptomatology, stress, quality of life (QOL) and exercise
      frequency, volume, and intensity were assessed in 114 females (18-33 years).
      Based on premenstrual symptoms (PMS), women were divided into high and low PMS
      groups and compared on stress, QOL and exercise variables. Results revealed women
      with high PMS had significantly more stress and poorer QOL than women with low
      PMS (p <.05 for both comparisons). Groups did not significantly differ on any of
      the exercise variables. Further analyses were performed to determine if exercise
      variables impacted PMS symptoms, stress and QOL reports in the high PMS group.
      While exercise volume and intensity did not impact any of the variables assessed,
      women with high PMS who reported exercising "sometimes" had more stress than
      women who reported exercising "often" or "never". This nonlinear relationship
      suggests that women with the worst symptoms may respond by exercising, while
      women who exercise often or never do not associate exercise with their symptoms.

PMID- 15256355
TI  - Lack of time for physical activity: perception or reality for African American
      and Hispanic women?
AB  - Lack of time is a well-known barrier to physical activity. It is not known,
      however, whether this barrier reflects actual time commitments. This study
      examined time commitments of women and assessed the relationship between time
      commitments and perceived lack of time for physical activity. Participants were
      249 African American and Hispanic women, aged 45 to 70 years. These women devoted
      much of their time to their responsibilities as workers, housekeepers, mothers
      and wives. They also spent 28 hours per week in sedentary leisure-time activity.
      Actual time commitments did not predict perceived lack of time for physical
      activity. These findings can be used to address the misperceptions of women about
      time available to them for physical activity.

PMID- 15256356
TI  - Attitudes toward cervical cancer screening among Muslim women: a pilot study.
AB  - BACKGROUND: Immigrant Muslim women have low rates of health care utilization,
      especially preventive care such as breast exams, mammograms, and cervical cancer
      screening. Religious and cultural beliefs, such as the value placed on modesty
      and premarital virginity, contribute to reluctance to seek health care. In
      addition, it has been unclear whether discussions of health care behavior that
      involve sexuality and reproductive health would be welcomed among immigrant
      Muslim women. PURPOSES: (1) To examine the impact of religious and cultural
      values on health care behavior of Muslim women from immigrant backgrounds in the
      San Francisco Bay Area, particularly with regard to cervical cancer screening;
      (2) To determine whether these women would welcome discussing values and beliefs
      regarding sexuality and reproductive health. METHODS: Our key informants were
      five Muslim women who identified pelvic and Pap smear screening exams as major
      sources of anxiety for their community, and therefore major barriers to health
      care. Three focus groups were then convened, including 15 women ages 18-25, to
      discuss these issues in more detail. RESULTS: Many Muslim women from immigrant
      backgrounds face challenges in obtaining adequate health care due to some common
      barriers of language, transportation, insurance, and family pressures.
      Additionally, many Muslim women resist screening practices that are the standard
      in the US but which threaten their cultural and religious values. Equally
      important, many health care professionals contribute to the women's challenges by
      making inappropriate recommendations regarding physical exams and reproductive
      health. The women were enthusiastic and candid in discussing these highly
      sensitive and taboo topics.

PMID- 15256357
TI  - Sexual assault in the lives of urban sex workers: a descriptive and comparative
      analysis.
AB  - This exploratory study contributes to the sparse literature on sexually assaulted
      sex workers. We examined 462 sexual assault cases seen at an emergency department
      based sexual assault service and reported to the police between 1993 and 1997.
      More than one fifth of victims were sex workers. We compared them to other
      victims on victim characteristics, assault characteristics, and medical-legal
      findings. Relative to other victims, sex workers were younger, had lower incomes,
      and were more likely to be heroin and/or cocaine users. They suffered a greater
      number of injuries and forensic samples collected from their bodies were more
      likely to test positive for sperm and/or semen. These victims were also less
      likely to have been using alcohol and/or marijuana prior to the assault and to be
      emotionally expressed during the medical- legal examination. The substantial
      proportion of sex workers in the study population suggests that attention to
      their particular needs should be an important part of hospital-based sexual
      assault services. Clinical implications and directions for future research are
      discussed.

PMID- 15256358
TI  - Embodied minds, restless spirits: mid-life rural women speak of their health.
AB  - This manuscript explores mid-life women's views of corporeality and the links
      that these have to their health. Using ethnographic interview techniques,
      community based interviewers talked with 24 women from rural settings. Our
      findings suggest that mid-life women have an embodied view of their minds and
      spirits, and that dualism is generally reserved for thinking about and
      interacting with the biomedical system. They have a sense of themselves as unique
      individuals who have a large role in caregiving, multiple other roles, and have
      luck but also agency in and control of their health and well-being. Motion was a
      strong theme throughout the interviews. Women embraced this mobility as a
      characteristic of their well-being as they coped with multiple changes associated
      with mid-life. In contrast to what some philosophers maintain, women seem to
      partner both corporeal changes and metaphor. While the sample was limited in
      scope, the findings support the importance to women's health of understanding the
      intersections between compositional and contextual variables in various settings.

PMID- 15256359
TI  - Synaptic transmission in simple motility reflex pathways excited by distension in
      guinea pig distal colon.
AB  - We examined specific receptor/transmitter combinations used at functionally
      identified synapses in ascending and descending reflex pathways of guinea pig
      distal colon. Excitatory (EJPs) or inhibitory junction potentials (IJPs) were
      recorded intracellularly from nicardipine-paralyzed circular smooth muscle in
      either the oral or anal recording chamber of a three-chambered organ bath,
      respectively. Blockade of synaptic transmission in the central chamber with a
      0.25 mM Ca2+/12 mM Mg2+ solution abolished EJPs evoked by distension applied
      either in the central or the far (anal) chamber. IJPs evoked by distension in the
      central or the far (oral) chamber were depressed to approximately 50% of control.
      Hexamethonium (nicotinic receptor antagonist, 200 microM) in the central chamber
      reduced IJPs evoked by far or central distension to 50%, whereas EJPs evoked by
      far distension were abolished and EJPs evoked by central distension were reduced
      to 70% of control. Hexamethonium in the recording chambers reduced both IJPs and
      EJPs evoked by central distension to approximately 50%. EJPs in the ascending
      pathway were unaffected by blockade of muscarinic receptors in the central
      chamber or blockade of neurokinin 3 tachykinin receptors in this or the recording
      chamber. In the descending pathway, blockade of P2 receptors in the same chambers
      had only a minor effect on distension-evoked IJPs. Thus some intrinsic sensory
      neurons of guinea pig colon have long descending projections (>30 mm), but
      ascending projections of <15 mm. In contrast to the ileum, transmission between
      ascending or descending interneurons and from sensory neurons to descending
      interneurons is predominantly via nicotinic receptors; but transmission to
      inhibitory or excitatory motoneurons and from sensory neurons to ascending
      interneurons involves nicotinic and other unidentified receptors.

PMID- 15256360
TI  - Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation.
AB  - TNF-alpha is a cytokine produced during gastric mucosal injury. We examined
      whether TNF-alpha could promote mucosal repair by stimulation of epithelial cell
      proliferation and explored further the underlying mechanisms in a rat gastric
      mucosal epithelial cell line (RGM-1). TNF-alpha treatment (1-10 ng/ml) for 12 or
      24 h significantly increased cell proliferation but did not induce apoptosis in
      RGM-1 cells. TNF-alpha treatment significantly increased cytosolic phospholipase
      A(2) and cyclooxygenase-2 (COX-2) protein expression and PGE(2) level but did not
      affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in
      RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also
      increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF
      alpha on cell proliferation, which was associated with a significant decrease in
      cellular COX-2 expression and PGE(2) level. A selective COX-2 inhibitor 3-(3
      fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-(5)H-furan-2-one (DFU) by
      itself had no effect on basal cell proliferation but significantly reduced the
      stimulatory effect of TNF-alpha on RMG-1 cells. Combination of dexamethasone and
      DFU did not produce an additive effect. PGE(2) significantly reversed the
      depressive action of dexamethasone on cell proliferation. These results suggest
      that TNF-alpha plays a regulatory role in epithelial cell repair in the gastric
      mucosa via the TNF-alpha receptor and activation of the arachidonic acid/PG
      pathway.

PMID- 15256361
TI  - Agonist-induced polarized trafficking and surface expression of the adenosine 2b
      receptor in intestinal epithelial cells: role of SNARE proteins.
AB  - Adenosine, acting through the A2b receptor, induces vectorial chloride and IL-6
      secretion in intestinal epithelia and may play an important role in intestinal
      inflammation. We have previously shown that apical or basolateral adenosine
      receptor stimulation results in the recruitment of the A2b receptor to the plasma
      membrane. In this study, we examined domain specificity of recruitment and the
      role of soluble N-ethylmaleimide (NEM) attachment receptor (SNARE) proteins in
      the agonist-mediated recruitment of the A2b receptor to the membrane. The colonic
      epithelial cell line T84 was used because it only expresses the A2b-subtype
      adenosine receptor. Cell fractionation, biotinylation, and electron microscopic
      studies showed that the A2b receptor is intracellular at rest and that apical or
      basolateral adenosine stimulation resulted in the recruitment of the receptor to
      the apical membrane. Upon agonist stimulation, the A2b receptor is enriched in
      the vesicle fraction containing vesicle-associated membrane protein (VAMP)-2.
      Furthermore, in cells stimulated with apical or basolateral adenosine, we
      demonstrate a complex consisting of VAMP-2, soluble NEM-sensitive factor
      attachment protein (SNAP)-23, and A2b receptor that is coimmunoprecipitated in
      cells stimulated with adenosine within 5 min and is no longer detected within 15
      min. Inhibition of trafficking with NEM or nocodazole inhibits cAMP synthesis
      induced by apical or basolateral adenosine by 98 and 90%, respectively. cAMP
      synthesis induced by foskolin was not affected, suggesting that generalized
      signaling is not affected under these conditions. Collectively, our data suggest
      that 1) the A2b receptor is intracellular at rest; 2) apical or basolateral
      agonist stimulation induces recruitment of the A2b receptor to the apical
      membrane; 3) the SNARE proteins, VAMP-2 and SNAP-23, participate in the
      recruitment of the A2b receptor; and 4) the SNARE-mediated recruitment of the A2b
      receptor may be required for its signaling.

PMID- 15256362
TI  - Obese and diabetic db/db mice develop marked liver fibrosis in a model of
      nonalcoholic steatohepatitis: role of short-form leptin receptors and
      osteopontin.
AB  - Obesity and type 2 diabetes are associated with nonalcoholic steatohepatitis
      (NASH), but an obese/diabetic animal model that mimics human NASH remains
      undefined. We examined the induction of steatohepatitis and liver fibrosis in
      obese and type 2 diabetic db/db mice in a nutritional model of NASH and
      determined the relationship of the expressions of osteopontin (OPN) and leptin
      receptors to the pathogenesis of NASH. db/db mice and the corresponding lean and
      nondiabetic db/m mice were fed a diet deficient in methionine and choline (MCD
      diet) or control diet for 4 wk. Leptin-deficient obese and diabetic ob/ob mice
      fed similar diets were used for comparison. MCD diet-fed db/db mice exhibited
      significantly greater histological inflammation and higher serum alanine
      aminotransferase levels than db/m and ob/ob mice. Trichrome staining showed
      marked pericellular fibrosis in MCD diet-fed db/db mice but no significant
      fibrosis in db/m or ob/ob mice. Collagen I mRNA expression was increased 10-fold
      in db/db mice, 4-fold in db/m mice, and was unchanged in ob/ob mice. mRNA
      expressions of OPN, TNF-alpha, TGF-beta, and short-form leptin receptors (Ob-Ra)
      were significantly increased in db/db mice compared with db/m or ob/ob mice.
      Parallel increases in OPN and Ob-Ra protein levels were observed in db/db mice.
      Cultured hepatocytes expressed only Ob-Ra, and leptin stimulated OPN mRNA and
      protein expression in these cells. In conclusion, our results demonstrate the
      development of an obese/diabetic experimental model for NASH in db/db mice and
      suggest an important role for Ob-Ra and OPN in the pathogenesis of NASH.

PMID- 15256363
TI  - Skeletal muscle atrophy is associated with an increased expression of myostatin
      and impaired satellite cell function in the portacaval anastamosis rat.
AB  - Proliferation and differentiation of satellite cells are critical in the
      regeneration of atrophied muscle following immobilization and aging. We
      hypothesized that impaired satellite cell function is responsible for the atrophy
      of skeletal muscle also seen in cirrhosis. Myostatin and insulin-like growth
      factor 1 (IGF1) have been identified to be positive and negative regulators,
      respectively, of satellite cell function. Using a rat model of cirrhosis
      [portacaval anastamosis (PCA)] and sham-operated controls, we examined the
      expression of myostatin, its receptor activinR2b, and its downstream messenger
      cyclin-dependent kinase inhibitor p21 (CDKI p21) as well as IGF1 and its receptor
      in the gastrocnemius muscle. Expression of PCNA, a marker of proliferation, and
      myogenic regulatory factors (myoD, myf5, and myogenin), markers of
      differentiation of satellite cells, were also measured. Real- time PCR for mRNA
      and Western blot assay for protein quantification were performed. PCA rats had
      lower body weight and gastrocnemius weight compared with sham animals (P < 0.05).
      PCNA and myogenic regulatory factors were lower in PCA rats (P < 0.05).
      Myostatin, activinR2b, and CDKI p21 were higher in the PCA animals (P < 0.05).
      The expression of IGF1 and its receptor was lower in liver and skeletal muscle of
      PCA animals (P < 0.05). These data suggest that skeletal muscle atrophy seen in
      the portacaval shunted rats is a consequence of impaired satellite cell
      proliferation and differentiation mediated, in part, by higher myostatin and
      lower IGF1 expression.

PMID- 15256364
TI  - Gastrointestinal nitric oxide generation in germ-free and conventional rats.
AB  - Nitric oxide (NO) is a central mediator of various physiological events in the
      gastrointestinal tract. The influence of the intestinal microflora for NO
      production in the gut is unknown. Bacteria could contribute to this production
      either by stimulating the mucosa to produce NO, or they could generate NO
      themselves. Using germ-free and conventional rats, we measured gaseous NO
      directly in the gastrointestinal tract and from the luminal contents using a
      chemiluminescence technique. Mucosal NO production was studied by using an NO
      synthase (NOS) inhibitor, and to evaluate microbial contribution to the NO
      generation, nitrate was given to the animals. In conventional rats, luminal NO
      differed profoundly along the gastrointestinal tract with the greatest
      concentrations in the stomach [>4,000 parts per billion (ppb)] and cecum
      (approximately 200 ppb) and lower concentrations in the small intestine and colon
      (< or =20 ppb). Cecal NO correlated with the levels in incubated luminal
      contents. NOS inhibition lowered NO levels in the colon, without affecting NO in
      the stomach and in the cecum. Gastric NO increased greatly after a nitrate load,
      proving it to be a substrate for NO generation. In germ-free rats, NO was low (<
      or =30 ppb) throughout the gastrointestinal tract and absent in the incubated
      luminal contents. NO also remained low after a nitrate load. Our results
      demonstrate a pivotal role of the intestinal microflora in gastrointestinal NO
      generation. Distinctly compartmentalized qualitative and quantitative NO levels
      in conventional and germ-free rats reflect complex host microbial cross talks,
      possibly making NO a regulator of the intestinal eco system.

PMID- 15256365
TI  - The gastrointestinal tract "tastes" nutrients: evidence from the intestinal taste
      aversion paradigm.
AB  - To develop and use a behavioral paradigm for assessments of what nutrient
      properties are detected by intestinal chemoreceptors, we combined features of the
      "electronic esophagus" preparation (Elizalde G and Sclafani A. Physiol Behav 47:
      63-77, 1990) and the conditioned taste aversion protocol (Garcia J and Koelling
      RA. Psychon Sci 4: 123-124, 1966). In four experiments, separate groups of food
      deprived rats with gastric (experiments 1-4) or duodenal (experiment 4) catheters
      were infused with either carbohydrates (maltodextrin) or fats (corn oil) into
      their stomachs or small intestines, either while they consumed nonnutritive
      flavored solutions (experiments 1 and 2) or in the absence of any intake
      (experiments 3 and 4). For some animals, one of the macronutrient infusions was
      paired with lithium chloride injections shown to support conventional conditioned
      aversions. After training, in various oral preference test trials, animals were
      given opportunities to taste and consume the nonnutritive solutions that had
      served as oropharyngeal conditioned stimuli as well as the nutrients that had
      been infused intragastrically, with or without poisoning, but never sampled by
      mouth. As previously established, preferences for the nonnutritive flavors were
      enhanced by association with intragastric infusions of macronutrients, with
      carbohydrates producing the greater preference. On first exposure to the two
      macronutrients for oral consumption, animals reduced their intake of the nutrient
      that had been previously poisoned when it was infused into the gastrointestinal
      tract. These results, along with additional controls, suggest that nutrient
      tastes detected in the intestines can be recognized centrally based on
      oropharyngeal gustatory stimulation.

PMID- 15256366
TI  - Osmoregulation of atrial myocytic ANP release: osmotransduction via cross-talk
      between L-type Ca2+ channel and SR Ca2+ release.
AB  - Hyperosmolality has been known to increase ANP release. However, its
      physiological role in the regulation of atrial myocytic ANP release and the
      mechanism by which hyperosmolality increases ANP release are to be defined. The
      purpose of the present study was to define these questions. Experiments were
      performed in perfused beating rabbit atria. Hyperosmolality increased atrial ANP
      release, cAMP efflux, and atrial dynamics in a concentration-dependent manner.
      The osmolality threshold for the increase in ANP release was as low as 10
      mosmol/kgH2O (approximately 3%) above the basal levels (1.55 +/- 1.71, 17.19 +/-
      3.11, 23.15 +/- 5.49, 54.04 +/- 11.98, and 62.00 +/- 13.48% for 10, 20, 30, 60,
      and 100 mM mannitol, respectively; all P < 0.01). Blockade of sarcolemmal L-type
      Ca2+ channel activity, which increased ANP release, attenuated hyperosmolality
      induced increases in ANP release (-13.58 +/- 4.68% vs. 62.00 +/- 13.48%, P <
      0.001) and cAMP efflux but not atrial dynamics. Blockade of the Ca2+ release from
      the sarcoplasmic reticulum, which increased ANP release, attenuated
      hyperosmolality-induced increases in ANP release (13.44 +/- 7.47% vs. 62.00 +/-
      13.48%, P < 0.01) and dynamics but not cAMP efflux. Blockades of Na+-K+-2Cl-
      cotransporter, Na+/H+ exchanger, and Na+/Ca2+ exchanger had no effect on
      hyperosmolality-induced increase in ANP release. The present study suggests that
      hyperosmolality regulates atrial myocytic ANP release and that the mechanism by
      which hyperosmolality activates ANP release is closely related to the cross-talk
      between the sarcolemmal L-type Ca2+ channel activity and sarcoplasmic reticulum
      Ca2+ release, possibly inactivation of the L-type Ca2+ channels.

PMID- 15256367
TI  - Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity,
      and lipemia in absence of glucocorticoids.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists improve
      insulin sensitivity and lipemia partly through enhancing adipose tissue
      proliferation and capacity for lipid retention. The agonists also reduce local
      adipose glucocorticoid production, which may in turn contribute to their
      metabolic actions. This study assessed the effects of a PPARgamma agonist in the
      absence of glucocorticoids (adrenalectomy, ADX). Intact, ADX, and intact pair-fed
      (PF) rats were treated with the PPARgamma agonist rosiglitazone (RSG) for 2 wk.
      RSG increased inguinal (subcutaneous) white (50%) and brown adipose tissue (6
      fold) weight but not that of retroperitoneal (visceral) white adipose tissue. ADX
      but not PF reduced fat accretion in both inguinal and retroperitoneal adipose
      depots but did not affect brown adipose mass. RSG no longer increased inguinal
      weight in ADX and PF rats but increased brown adipose mass, albeit less so than
      in intact rats. RSG increased cell proliferation in white (3-fold) and brown
      adipose tissue (6-fold), as assessed microscopically and by total DNA, an effect
      that was attenuated but not abrogated by ADX. RSG reduced the expression of the
      glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta
      HSD1) in all adipose depots. RSG improved insulin sensitivity (reduction in
      fasting insulin and homeostasis model assessment of insulin resistance, both 
      50%) and triacylglycerolemia (-75%) regardless of the glucocorticoid status,
      these effects being fully additive to those of ADX and PF. In conclusion, RSG
      partially retained its ability to induce white and brown adipose cell
      proliferation and brown adipose fat accretion and further improved insulin
      sensitivity and lipemia in ADX rats, such effects being therefore independent
      from the PPARgamma-mediated modulation of glucocorticoids.

PMID- 15256368
TI  - Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in
      cardiomyocytes isolated from rabbits.
AB  - Autoantibodies against muscarinic and adrenergic receptors have been found in the
      sera of patients with idiopathic dilated cardiomyopathy (IDC) and Chagas disease,
      but it is still unclear whether they can functionally interact with their
      respective receptors to modulate cardiac functions. In this study, our goal was
      to detect the presence of those antibodies in the sera of patients with IDC and
      characterize their electrophysiological effects on cardiomyocytes from rabbits.
      By using ELISA immunoassays, we detected high titers of antibodies against
      muscarinic M2 receptors in the sera of all IDC patients, whereas the detection of
      antibodies against the beta1-receptor occurred in 50% of them.
      Electrophysiological experiments using the whole cell configuration of the patch
      clamp technique showed that sera from 43% of IDC patients induced a significant
      decrease (approximately 26%) in isoproterenol-stimulated L-type Ca2+ currents in
      rabbit ventricular myocytes, whereas the sera from healthy blood donors failed to
      do so. As expected, IDC sera also decreased the action potential duration (by
      10.5%) due to a shortening of the plateau phase. Sera that reduced isoproterenol
      stimulated L-type Ca2+ currents did not cause any effect on K+ currents. We
      conclude that sera from IDC patients have autoantibodies, which interact with
      muscarinic M2 receptors of rabbit cardiomyocytes, acting in an agonist-like
      fashion. This action results in changes in electrogenesis, which, as often
      observed in patients with IDC, could initiate ventricular arrhythmias that lead
      to sudden death.

PMID- 15256369
TI  - Continuous peripheral resistance measurement during hemorrhagic hypotension.
AB  - We tested the hypotheses that continuous total peripheral resistance (TPR)
      measurements are superior to intermittent data collection and that variables
      related to TPR can be used to distinguish between survivors and nonsurvivors
      (NS), respectively, of prolonged hemorrhagic hypotension (HH). One week after a
      transit-time ultrasound probe was implanted on their ascending aortas, 21 rats
      were subjected to 4 h of HH at 40 mmHg. Measurements were made before and up to 4
      h after initiation of HH. Additional bleeding or Ringer L-lactate (RL) infusion
      was used to maintain HH. TPR was continuously measured online using recordings of
      blood flow and arterial pressure. Approximately 67% of the rats survived > or =3
      h; others were considered NS. Data collected at 30-min intervals failed to detect
      the maximum value of TPR (TPRmax). The times to reach TPRmax were similar for
      survivors and NS and were strongly correlated with the bleeding end points and
      with the RL infusion-onset times. However, survivors showed higher TPRmax values
      than NS (P <0.005) and had a significantly longer period than NS during which TPR
      was above baseline level (116 +/- 20 vs. 51 +/- 10 min). In conclusion, 1) the
      transit-time ultrasound technique at high sampling rate allowed continuous and
      accurate real-time monitoring of TPR, 2) the bleeding end point and RL infusion
      onset times may be used as surrogates of the time to TPRmax, 3) TPRmax of
      survivors and NS could be detected only using a continuous TPR measurement, and
      4) differences between survivors and NS could be revealed by the continuous TPR
      curve.

PMID- 15256370
TI  - Role of caveolae in ouabain-induced proliferation of cultured vascular smooth
      muscle cells of the synthetic phenotype.
AB  - We have shown earlier that low concentrations of ouabain that do not perturb the
      ionic milieu can initiate proliferation of vascular smooth muscle cells (VSMCs)
      in the synthetic phenotype from three different species: canine, rodent, and
      human. This effect occurs by activation of Src and the epidermal growth factor
      receptor (EGFR), and thus supports the concept of an additional, nonionic,
      transducing function of the Na pump. The present study presents data suggesting
      that such activation occurs through specific Na pump sites localized to the
      caveolae, and subsequent interactions with selected signaling proteins resident
      within the same membrane microdomain. Our data show that at rest, 30% of the
      total number of Na pumps are concentrated within the caveolae. When the various
      VSMCs were treated with proliferating concentrations of ouabain, the key protein
      content in isolated caveolae was increased. However, the recruited proteins were
      different between the different tissues. Thus ouabain activated the recruitment
      of both the Na pump alpha1-subunit and EGFR in the caveolae from rat A7r5 cells,
      whereas in both human and canine cells, ouabain activated the recruitment of Src,
      with the caveolar content of the other proteins remaining constant. These data
      demonstrate that ouabain interacts with the alpha1-subunit of the Na pump that
      resides within the caveolar domain, and such interaction selectively recruits
      signal transducing proteins to this microdomain resulting in their activation,
      which is necessary for the initiation of the proliferative cascade.

PMID- 15256371
TI  - Selective decontamination of the digestive tract attenuated the myocardial
      inflammation and dysfunction that occur with burn injury.
AB  - This study examined the effects of oral antibiotics to selectively decontaminate
      the digestive tract (SDD) on postburn myocardial signaling, inflammation, and
      function. We hypothesized that antibiotic therapy to eliminate pathogens from the
      gastrointestinal (GI) tract would reduce myocardial inflammatory responses and
      improve postburn myocardial performance. Sprague-Dawley rats received polymyxin E
      (15 mg), tobramycin (6 mg), and 5-flucytosin (100 mg) by oral gavage twice daily
      for 3 days preburn and 24 h postburn. Experimental groups included 1) sham burn
      given vehicle (3 ml water), 2) sham plus SDD, 3) burn over 40% total body surface
      area (TBSA) plus SDD, and 4) burn over 40% TBSA given vehicle. All burns received
      lactated Ringer solution (4 mg.kg(-1).%burn(-1)); myocardial signaling
      (PKCepsilon/p38 MAPK/NF-kappaB) was studied 2, 4, and 24 h postburn; and cytokine
      secretion (systemic and myocyte secreted cytokines, ELISA) and cardiac function
      were examined 24 h postburn. Vehicle-treated burn injury increased myocardial
      PKCepsilon/p38 MAPK expression, promoted NF-kappaB nuclear translocation,
      promoted TNF-alpha, IL-1beta, IL-6, and IL-10 secretion, and impaired myocardial
      function. SDD attenuated burn-related proinflammatory myocardial signaling,
      cytokine secretion, and myocardial contractile defects. Our data suggest that
      burn-related loss of GI barrier function and translocation of microbial products
      serve as upstream mediators of postburn myocardial inflammatory signaling and
      dysfunction.

PMID- 15256372
TI  - Doxycycline inducible expression of SERCA2a improves calcium handling and reverts
      cardiac dysfunction in pressure overload-induced cardiac hypertrophy.
AB  - Delayed cardiac relaxation in failing hearts has been attributed to reduced
      activity and/or expression of sarco(endo)plasmic reticulum Ca2+-ATPase 2a
      (SERCA2a). Although constitutive overexpression of SERCA2a has proven effective
      in preventing cardiac dysfunction, it is unclear whether increasing SERCA2a
      expression in hearts with preexisting hypertrophy will be therapeutic. To test
      this hypothesis, we generated a binary transgenic (BTG) system that allows
      tetracycline-inducible, cardiac-specific SERCA2a expression. In this system (tet
      on SERCA2a), a FLAG-tagged SERCA2a transgene is expressed in the presence of
      doxycycline (Dox) but not in the absence of Dox (2.3-fold more mRNA, 45% more
      SERCA2a protein). Calcium transients measured in isolated cardiac myocytes from
      nonbanded Dox-treated BTG mice showed an accelerated calcium decline and an
      increased systolic Ca2+ peak. Sarcoplasmic reticulum (SR) calcium loading was
      increased by 45% in BTG mice. In the presence of pressure overload (aortic
      banding), echocardiographic analysis revealed that expression of SERCA2a-FLAG
      caused an improvement in fractional shortening. SERCA2a-FLAG expression
      alleviated the resultant cardiac dysfunction. This was illustrated by an increase
      in the rate of decline of the calcium transient. Cell shortening and SR calcium
      loading were also improved in cardiac myocytes isolated from banded BTG mice
      after SERCA2a overexpression. In conclusion, we generated a novel transgenic
      mouse that conditionally overexpresses SERCA2a. This model is suitable for both
      long- and short-term studies of the effects of controlled SERCA2a expression on
      cardiac function. In addition, inducible overexpression of SERCA2a improved
      cardiac function and calcium handling in mice with established contractile
      dysfunction.

PMID- 15256373
TI  - Acetaminophen and myocardial infarction in dogs.
AB  - The hypothesis that acetaminophen can reduce necrosis during myocardial
      infarction was tested in male dogs. Two groups were studied: vehicle- (n=10) and
      acetaminophen-treated (n=10) dogs. All dogs were obtained from the same vendor,
      and there were no significant differences in their ages (18 +/- 2 mo), weights
      (24 +/- 1 kg), or housing conditions. Selected physiological data, e.g., coronary
      blood flow, nonspecific collateral flow, epicardial temperature, heart rate,
      systemic mean arterial pressure, left ventricular developed pressure, the maximal
      first derivative of left ventricular developed pressure, blood gases, and pH,
      were collected at baseline and during regional myocardial ischemia and
      reperfusion. There were no significant differences in coronary blood flow,
      nonspecific collateral flow, epicardial temperature, heart rate, systemic mean
      arterial pressure, or blood gases and pH between the two groups at any of the
      three time intervals, even though there was a trend toward improved function in
      the presence of acetaminophen. Infarct size, the main objective of the
      investigation, was markedly and significantly reduced by acetaminophen. For
      example, when expressed as a percentage of ventricular wet weight, infarct size
      was 8 +/- 1 versus 3 +/- 1%(P <0.05) in vehicle- and acetaminophen-treated
      hearts, respectively. When infarct size was expressed as percentage of the area
      at risk, it was 35 +/- 3 versus 13 +/- 2% (P <0.05) in vehicle- and acetaminophen
      treated groups, respectively. When area at risk was expressed as percentage of
      total ventricular mass, there were no differences in the two groups. Results
      reveal that the recently reported cardioprotective properties of acetaminophen in
      vitro can now be extended to the in vivo arena. They suggest that it is necessary
      to add acetaminophen to the growing list of pharmaceuticals that possess
      cardioprotective efficacy in mammals.

PMID- 15256374
TI  - Loss of atrial contractility is primary cause of atrial dilatation during first
      days of atrial fibrillation.
AB  - Atrial fibrillation (AF) induces a progressive dilatation of the atria which in
      turn might promote the arrhythmia. The mechanism of atrial dilatation during AF
      is not known. To test the hypothesis that loss of atrial contractile function is
      a primary cause of atrial dilatation during the first days of AF, eight goats
      were chronically instrumented with epicardial electrodes, a pressure transducer
      in the right atrium, and piezoelectric crystals to measure right atrial diameter.
      AF was induced with the use of repetitive burst pacing. Atrial contractility was
      assessed during sinus rhythm, atrial pacing (160-, 300-, and 400-ms cycle
      length), and electrically induced AF. The compliance of the fibrillating right
      atrium was measured during unloading the atria with diuretics and loading with 1
      liter of saline. All measurements were repeated after 6, 12, and 24 h of AF and
      then once a day during the first 5 days of AF. Recovery of the observed changes
      after spontaneous cardioversion was also studied. After 5 days of AF, atrial
      contractility during sinus rhythm or slow atrial pacing was greatly reduced.
      During rapid pacing (160 ms) or AF, the amplitude of the atrial pressure waves
      had declined to 20% of control. The compliance of the fibrillating atria
      increased twofold, whereas the right atrial pressure was unchanged. As a result,
      the mean right atrial diameter increased by approximately 12%. All changes were
      reversible within 3 days of sinus rhythm. We conclude that atrial dilatation
      during the first days of AF is due to an increase in atrial compliance caused by
      loss of atrial contractility during AF. Atrial compliance and size are restored
      when atrial contractility recovers after cardioversion of AF.

PMID- 15256375
TI  - N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in
      vivo.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural inhibitor of
      pluripotent hematopoietic stem cell proliferation, has been suggested as capable
      of promoting an angiogenic response. We studied whether Ac-SDKP stimulates
      endothelial cell proliferation, migration, and tube formation; enhances
      angiogenic response in the rat cornea after implantation of a tumor spheroid; and
      increases capillary density in rat hearts with myocardial infarction (MI). In
      vitro, an immortal BALB/c mouse aortic endothelial 22106 cell line was used to
      determine the effects of Ac-SDKP on endothelial cell proliferation and migration
      and tube formation. In vivo, a 9L-gliosarcoma cell spheroid (250-300 microm in
      diameter) was implanted in the rat cornea and vehicle or Ac-SDKP (800 microg.kg(
      1).day(-1) ip) infused via osmotic minipump. Myocardial capillary density was
      studied in rats with MI given either vehicle or Ac-SDKP. We found that Ac-SDKP 1)
      stimulated endothelial cell proliferation and migration and tube formation in a
      dose-dependent manner, 2) enhanced corneal neovascularization, and 3) increased
      myocardial capillary density. Endothelial cell proliferation and angiogenesis
      stimulated by Ac-SDKP could be beneficial in cardiovascular diseases such as
      hypertension and MI. Furthermore, because Ac-SDKP is mainly cleaved by ACE, it
      may partially mediate the cardioprotective effect of ACE inhibitors.

PMID- 15256376
TI  - Impaired muscle metaboreflex-induced increases in ventricular function in heart
      failure.
AB  - We investigated to what extent heart failure alters the ability of the muscle
      metaboreflex to improve ventricular function. Dogs were chronically instrumented
      to monitor mean arterial pressure (MAP), cardiac output (CO), heart rate (HR),
      stroke volume (SV), and central venous pressure (CVP) at rest and during mild
      treadmill exercise (3.2 km/h) before and during reductions in hindlimb blood flow
      imposed to activate the muscle metaboreflex. These control experiments were
      repeated at constant heart rate (ventricular pacing 225 beats/min) and at
      constant heart rate coupled with a beta-adrenergic blockade (atenolol, 2 mg/kg
      iv) in normal animals and in the same animals after the induction of heart
      failure (HF, induced via rapid ventricular pacing). In control experiments in
      normal animals, metaboreflex activation caused tachycardia with no change in SV,
      resulting in large increases in CO and MAP. At constant HR, large increases in CO
      still occurred via significant increases in SV. Inasmuch as CVP did not change in
      this setting and that beta-adrenergic blockade abolished the reflex increase in
      SV at constant HR, this increase in SV likely reflects increased ventricular
      contractility. In contrast, after the induction of HF, much smaller increases in
      CO occurred with metaboreflex activation because, although increases in HR still
      occurred, SV decreased thereby limiting any increase in CO. At constant HR, no
      increase in CO occurred with metaboreflex activation even though CVP increased
      significantly. After beta-adrenergic blockade, CO and SV decreased with
      metaboreflex activation. We conclude that in HF, the ability of the muscle
      metaboreflex to increase ventricular function via both increases in contractility
      as well as increases in filling pressure are markedly impaired.

PMID- 15256377
TI  - Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells.
AB  - The glycocalyx layer on the surface of an endothelial cell is an interface
      barrier for uptake of macromolecules, such as low-density lipoprotein and
      albumin, in the cell. The shear-dependent uptake of macromolecules thus might
      govern the function of the glycocalyx layer. We therefore studied the effect of
      glycocalyx on the shear-dependent uptake of macromolecules into endothelial
      cells. Bovine aorta endothelial cells were exposed to shear stress stimulus
      ranging from 0.5 to 3.0 Pa for 48 h. The albumin uptake into the cells was then
      measured using confocal laser scanning microscopy, and the microstructure of
      glycocalyx was observed using electron microscopy. Compared with the uptake into
      endothelial cells under static conditions (no shear stress stimulus), the albumin
      uptake at a shear stress of 1.0 Pa increased by 16% and at 3.0 Pa decreased by
      27%. Compared with static conditions, the thickness of the glycocalyx layer
      increased by 70% and the glycocalyx charge increased by 80% at a shear stress of
      3.0 Pa. The albumin uptake at a shear stress of 3.0 Pa for cells with a
      neutralized (no charge) glycocalyx layer was almost twice that of cells with
      charged layer. These findings indicate that glycocalyx influences the albumin
      uptake at higher shear stress and that glycocalyx properties (thickness and
      charge level) are involved with the shear-dependent albumin uptake process.

PMID- 15256378
TI  - Hemodynamic and sympathoadrenal responses to mental stress during nitric oxide
      synthesis inhibition.
AB  - Cardiovascular and sympathoadrenal responses to a reproducible mental stress test
      were investigated in eight healthy young men before and during intravenous
      infusion of the nitric oxide (NO) synthesis inhibitor N-monomethyl-L-arginine (L
      NMMA). Before L-NMMA, stress responses included significant increases in heart
      rate, mean arterial pressure, and cardiac output (CO) and decreases in systemic
      and forearm vascular resistance. Arterial plasma norepinephrine (NE) increased.
      At rest after 30 min of infusion of L-NMMA (0.3 mg.kg(-1).min(-1) iv), mean
      arterial pressure increased from 98 +/- 4 to 108 +/- 3 mmHg (P <0.001) because of
      an increase in systemic vascular resistance from 12.9 +/- 0.5 to 18.5 +/- 0.9
      units (P <0.001). CO decreased from 7.7 +/- 0.4 to 5.9 +/- 0.3 l/min (P <0.01).
      Arterial plasma NE decreased from 2.08 +/- 0.16 to 1.47 +/- 0.14 nmol/l. Repeated
      mental stress during continued infusion of L-NMMA (0.15 mg.kg(-1).min(-1))
      induced qualitatively similar cardiovascular responses, but there was a marked
      attenuation of the increase in mean arterial blood pressure, resulting in similar
      "steady-state" blood pressures during mental stress without and with NO blockade.
      Increases in heart rate and CO were attenuated, but stress-induced decreases in
      systemic and forearm vascular resistance were essentially unchanged. Arterial
      plasma NE increased less than during the first stress test. Thus the increased
      arterial tone at rest during L-NMMA infusion is compensated for by attenuated
      increases in blood pressure during mental stress, mainly through a markedly
      attenuated CO response and suppressed sympathetic nerve activity.

PMID- 15256379
TI  - Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid
      associated fetal loss: characterisation of beta 2-glycoprotein I binding to
      trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies
      in vitro.
AB  - BACKGROUND: Antiphospholipid antibodies reacting with beta2-glycoprotein I (beta
      2GPI) have been associated with recurrent fetal loss and pregnancy complications.
      OBJECTIVE: To investigate whether specific mutations in the phospholipid binding
      site of beta 2GPI might affect its binding to trophoblast and in turn the anti
      beta 2GPI antibody induced functional effects. METHODS: beta 2GPI adhesion to
      trophoblast was evaluated as human monoclonal IgM or polyclonal IgG anti-beta
      2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium;
      (2) in serum-free medium; (3) after serum starvation in the presence of purified
      human beta 2GPI; or (4) in the presence of beta 2GPI with single or multiple
      mutations in the amino acid loop Cys(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys(288). The
      effect of anti-beta 2GPI binding to trophoblast was evaluated as chorionic
      gonadotropin (hCG) mRNA expression, and protein release by RT-PCR and
      radioimmunoassay, respectively. RESULTS: beta 2GPI adhesion to trophoblast and
      its consequent recognition by the specific antibodies were inversely proportional
      to the mutation number in the phospholipid binding site. Anti-beta 2GPI
      antibodies reduced gonadotropin release, hormone dependent hCG mRNA expression,
      and protein synthesis in the presence of beta 2GPI, while the addition of the
      mutants or the absence of beta 2GPI had no effect. CONCLUSIONS: beta 2GPI binds
      to trophoblast in vitro through its fifth domain, as reported for endothelial
      cells, and can be recognised by anti-beta 2GPI antibodies; the antibody binding
      downregulates trophoblast hCG synthesis and secretion. Such a mechanism might
      contribute to defective placentation in women with fetal loss associated with the
      antiphospholipid syndrome.

PMID- 15256380
TI  - Inhibition of TNF alpha during maturation of dendritic cells results in the
      development of semi-mature cells: a potential mechanism for the beneficial
      effects of TNF alpha blockade in rheumatoid arthritis.
AB  - BACKGROUND: Dendritic cells orchestrate pivotal immunological processes mediated
      by the production of cytokines and chemokines. OBJECTIVE: To assess whether
      neutralisation of tumour necrosis factor alpha (TNF alpha) during maturation of
      dendritic cells affects their phenotype and behaviour, which might explain the
      beneficial effects of TNF alpha neutralisation in rheumatoid arthritis. METHODS:
      Immature and fully matured dendritic cells were cultured from blood monocytes
      from patients with rheumatoid arthritis and healthy controls following
      standardised protocols. TNF alpha was neutralised by addition of the p55 soluble
      TNF alpha receptor, PEGsTNFRI. The effect of TNF alpha neutralisation on the
      phenotype (CD14, CD16, CD32, CD64, CD80, CD83, CD86, and MHC) of dendritic cells
      was investigated by flow cytometry. Expression of chemokines (CCL17, CCL18,
      CCL19, CCL22, CCL3, and CXCL8) and production of IL1 beta and IL6 during
      dendritic cell differentiation and maturation were examined. RESULTS:
      Neutralisation of TNF alpha during the differentiation and maturation of
      dendritic cells did not result in an altered dendritic cell phenotype in the
      rheumatoid patients or the healthy controls. In contrast, the expression of
      CCL17, CCL18, CCL19, CCL22, CCL3, and CXCL8 by dendritic cells was significantly
      reduced when TNF alpha activity was inhibited during lipopolysaccharide triggered
      dendritic cell maturation. The production of IL1 beta and IL6 by mature dendritic
      cells was inhibited by PEGsTNFRI. CONCLUSIONS: Inhibition of TNF alpha activity
      during dendritic cell maturation leads to the development of semi-mature cells.
      These data suggest a novel pathway by which the neutralisation of TNF alpha might
      exert its therapeutic effects.

PMID- 15256381
TI  - Tree growth and competition in a Betula platyphylla-Larix cajanderi post-fire
      forest in central Kamchatka.
AB  - BACKGROUND AND AIMS: Fire is the dominant disturbance in central Kamchatka boreal
      forests, yet patterns and mechanisms of stand recovery have not been
      investigated. METHODS: Measurements were made of 1433 stems > or =1.3 m height
      and annual radial increments of 225 randomly selected trees in a 0.4-ha plot of a
      53-year-old fire-origin mixed-species stand to examine the spatio-temporal
      variation in establishment, growth, size inequality and the mode of competition
      among individual trees. Growth variations were related to tree size, age and
      local interference with neighbours. KEY RESULTS: Betula platyphylla formed the
      main canopy following a fire in 1947, with Larix cajanderi and Pinus pumila
      progressively reinvading the lower tree and shrub stratum. Most B. platyphylla
      originated from sprouts in small patches (polycormons) during the first 15 post
      fire years. Betula platyphylla had normal distributions of diameter and age
      classes, but negatively skewed height distribution, as expected from shade
      intolerant, pioneer species. Larix cajanderi had fewer tall and many short
      individuals. The smaller and younger B. platyphylla grew disproportionately more
      in diameter than larger trees from 1950 to 1975, and hence stem size inequalities
      decreased. The reverse trend was observed from 1995 to 2000: larger trees grew
      more, indicating an increasing asymmetry of competition for light. Betula
      platyphylla had steady diameter growth in the first 25 post-fire years, after
      which the growth declined in smaller trees. Neighbourhood analysis showed that
      the decline resulted from increased competition from taller neighbours.
      CONCLUSIONS: The observed growth patterns suggest that mode of interactions
      altered during stand development from early stages of weak competition for soil
      resources released by fire to later stages of asymmetric competition for light.
      Asymmetric crown competition started later than reported in other studies, which
      can be attributed to the lower stem density leaving much space for individual
      growth, greater relative importance of below-ground competition in this site of
      nutrient-poor volcanic soil, and the vegetative origin of B. platyphylla. Larix
      cajanderi growing under B. platyphylla had steady diameter growth during the
      first 20 years, after which growth declined. It is suggested that early
      succession fits the tolerance model of succession, while inhibition dominates in
      later stages.

PMID- 15256382
TI  - Reversible cigarette smoke extract-induced DNA damage in human lung fibroblasts.
AB  - Cigarette smoke contains thousands of chemicals, many of which may contribute to
      cytotoxicity and carcinogenesis. Using assays detecting DNA strand breaks
      (terminal transferase dUTP nick end labeling [TUNEL]) and DNA content (flow
      cytometry), we evaluated the genotoxic effect of cigarette smoke extract (CSE) on
      human fetal lung fibroblasts (HFL-1) cultured in three-dimensional collagen gels
      as well as in monolayer culture. When HFL-1 cells were exposed to CSE, DNA strand
      breaks were detected in most, as determined by TUNEL. This effect was dependent
      on CSE concentration, duration of CSE exposure, and the density of HFL-1 cells
      cast into the collagen gels. Buthionine sulfoximine (BSO), an inhibitor of
      glutathione synthesis, significantly increased DNA damage induced by 1% CSE, and
      N-acetylcysteine, a glutathione precursor, blocked 5% CSE from inducing DNA
      damage. After CSE exposure, most cells were TUNEL-positive, but DNA
      quantification revealed no hypodiploid cells, indicating that apoptosis was not
      occurring during the CSE exposure. CSE-induced DNA damage was reversible, and
      cells proliferated when CSE was removed after 24 h exposure. These results
      demonstrate that cigarette smoke can induce DNA damage in HFL-1 cells cultured in
      both three-dimensional collagen gels and monolayer cultures, and that oxidants
      likely play a role in this damage. Moreover, this DNA damage is reversible, with
      cells surviving and TUNEL positivity reversing when CSE is removed within 24 h.

PMID- 15256383
TI  - Cobalt induces hypoxia-inducible factor-1alpha expression in airway smooth muscle
      cells by a reactive oxygen species- and PI3K-dependent mechanism.
AB  - Cobalt can mimic hypoxia and has been implicated as a cause of lung defects.
      However, the effect of cobalt on airway smooth muscle (ASM) cells has not been
      analyzed in detail. In this article, we use primary cultures of ASM cells from
      rabbit trachea and show that exposure to cobalt chloride causes a rapid increase
      of the intracellular levels of hypoxia-inducible factor-1alpha, which is detected
      predominantly inside the nucleus. With the use of specific inhibitors, we
      demonstrate that induction of hypoxia-inducible factor-1alpha by cobalt depends
      on active protein synthesis but not transcription. Furthermore, wortmannin,
      LY294002, and N-acetyl-L-cysteine inhibit the effect of cobalt, suggesting that
      it involves the phosphatidylinositol 3 kinase pathway and production of reactive
      oxygen species. Interestingly, cobalt chloride attenuates the contractile
      response of rabbit airways induced by potassium chloride, but not by
      acetylcholine, suggesting a link between the cellular response to hypoxic stimuli
      and the contractile properties of ASM cells.

PMID- 15256384
TI  - Epidermal growth factor and trefoil factor family 2 synergistically trigger
      chemotaxis on BEAS-2B cells via different signaling cascades.
AB  - Injured areas of the respiratory epithelium are subject to rapid repair by the
      migration of adjacent epithelial cells, a process termed "restitution". Rapid re
      epithelialization is promoted by interactions between migrating cells and the
      extracellular matrix proteins. Furthermore, epidermal growth factor (EGF) as well
      as trefoil factor family (TFF) peptides are well known regulators of epithelial
      restitution due to their motogenic effects. Migration of the human bronchial
      epithelial cell line BEAS-2B in modified Boyden chambers was used as a model
      system for airway restitution. EGF or recombinant human TFF2 or TFF3 showed
      mainly chemotactic activity. The motogenic response was strictly dependent upon a
      haptotactic substrate, but to different degrees. EGF induced phosphorylation of
      extracellular signal-regulated kinases (ERK) 1/2, c-Jun-N-terminal kinase, p38,
      Akt, and p70S6K in BEAS-2B cells. Using specific inhibitors, the signaling
      cascades responsible for the motogenic response were shown to differ drastically
      when EGF was compared with TFF2. The motogenic effect of TFF2 was previously
      demonstrated to depend on ERK1/2 and protein kinase C activation; whereas the EGF
      triggered motogenic response was completely independent of ERK1/2 activation but
      sensitive to the inhibition of phosphoinositide 3-kinase, p38, protein kinase C,
      or nuclear factor kappaB. However, the motogenic effects of EGF and TFF2 are
      additive. These data suggest that luminal EGF and TFF peptides can act
      synergistically in the human respiratory epithelium to enhance rapid repair
      processes in the course of diseases such as asthma.

PMID- 15256385
TI  - Extracellular superoxide dismutase attenuates lipopolysaccharide-induced
      neutrophilic inflammation.
AB  - Extracellular superoxide dismutase (EC-SOD) is an abundant antioxidant in the
      lung and vascular walls. Previous studies have shown that EC-SOD attenuates lung
      injury in a diverse variety of lung injury models. In this study, we examined the
      role of EC-SOD in mediating lipopolysaccharide (LPS)-induced lung inflammation.
      We found that LPS-induced neutrophilic lung inflammation was exaggerated in EC
      SOD-deficient mice and diminished in mice that overexpressed EC-SOD specifically
      in the lung. Similar patterns were seen for bronchoalveolar lavage cytokines,
      such as tumor necrosis factor-alpha, keratinocyte-derived chemokines, and
      macrophage inflammatory protein-2 as well as expression of lung intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1, endothelial cell
      selectin, and platelet selectin. In a macrophage cell line, EC-SOD inhibited LPS
      induced macrophage cytokine release, but did not alter expression of
      intercellular adhesion molecules in endothelial cells. These results suggest that
      EC-SOD plays an important role in attenuating the inflammatory response in the
      lung most likely by decreasing release of proinflammatory cytokines from
      phagocytes.

PMID- 15256386
TI  - Beryllium-ferritin: lymphocyte proliferation and macrophage apoptosis in chronic
      beryllium disease.
AB  - A beryllium (Be)-ferritin adduct containing 270 pm of Be stimulated proliferation
      of bronchoalveolar lavage (BAL) lymphocytes from subjects with chronic beryllium
      disease (CBD) at concentrations 5-6 logs lower than the amounts of beryllium
      sulfate (BeSO4) needed to induce proliferation. We observed increased apoptotic
      CBD BAL macrophages after exposure to both BeSO4 (50 +/- 6%, mean +/- SEM, P
      <0.05 versus unstimulated controls) and Be-ferritin (40 +/- 2%), whereas only 2.0
      +/- 0.2% of BAL lymphocytes underwent activation-induced cell death. Be-ferritin
      also induced apoptosis in BAL macrophages from subjects with Be sensitization (25
      +/- 3%) and in the H36.12j hybrid macrophage cell line (15 +/- 2%). Be-ferritin
      induced lung macrophage CD95 (Fas) expression and the activation of intracellular
      caspase-3, -8 and -9. Thus, lung macrophages take up Be-ferritin, delivering
      physiologically relevant levels of Be that promote Be antigen presentation and
      macrophage apoptosis. Be-ferritin thereby serves as a "Trojan Horse," triggering
      proliferation of Be-ferritin-specific CBD BAL T cells. We hypothesize that Be
      ferritin exposure may result in persistent antigen exposure inducing Be-specific
      T cell clonal expansion and T cell helper type 1-type cytokine production and
      potentially explains the chronicity of CBD and its development years after
      environmental Be exposure has ceased.

PMID- 15256387
TI  - Mechanistic similarities between cultured cell models of cystic fibrosis and
      niemann-pick type C.
AB  - Recent data demonstrate that inhibition of 3-hydroxy-3-methylglutaryl-CoA
      reductase restores normal signal transducer and activator of transcription-1 and
      inducible nitric oxide synthase expression regulation in cystic fibrosis (CF)
      cells through the modulation of RhoA function. These findings lead to the
      hypothesis that alterations in the cholesterol synthesis pathway may be an
      initiating factor in CF-related cell signaling regulation. A disease with a known
      lesion in the cholesterol synthesis pathway is Niemann-Pick type C (NPC). The
      hypothesis of this study is that CF cells and NPC fibroblasts share a common
      mechanistic lesion and should exhibit similar cell signaling alterations. NPC
      fibroblasts exhibit similar alterations in signal transducer and activator of
      transcription-1, RhoA, SMAD3, and nitric oxide synthase protein expression that
      characterize CF. Further comparison reveals NPC-like accumulation of free
      cholesterol in two cultured models of CF epithelial cells. These data identify
      novel signaling changes in NPC, demonstrate the cholesterol-synthesis pathway is
      a likely source of CF-related cell signaling changes, and that cultured CF cells
      exhibit impaired cholesterol processing.

PMID- 15256388
TI  - Connective tissue growth factor is crucial to inducing a profibrotic environment
      in "fibrosis-resistant" BALB/c mouse lungs.
AB  - The individual susceptibility to pulmonary fibrosis (PF) remains a mystery,
      suggesting a role for genetic predisposition. The pathogenesis of PF involves a
      multitude of factors mediating crosstalk between various tissue components. Some
      factors, such as transforming growth factor beta, are recognized as key elements
      in the process, whereas the role of others, such as connective tissue growth
      factor (CTGF), is unclear. We investigated if Balb/c mice, known to be fibrosis
      resistant partly due to lack of CTGF induction upon stimulation with bleomycin,
      can be transformed into fibrosis-sensitive individuals by generation of a CTGF
      rich environment using transient overexpression of CTGF by adenoviral gene
      transfer (AdCTGF). We show that AdCTGF is not sufficient to cause fibrosis, and
      that bleomycin challenge results in inflammation, but not fibrosis, in Balb/c
      mouse lungs. This inflammation is accompanied by lower levels of CTGF and tissue
      inhibitor of metalloproteinase-1 gene expression compared with fibrosis-prone
      C57BL/6 mice. However, concomitant administration of AdCTGF and bleomycin leads
      to a persistent upregulation of tissue inhibitor of metalloproteinase-1 gene and
      a significant fibrotic response in Balb/c similar to that in C57BL/6 mice. We
      propose that CTGF is an important mediator in the pathogenesis of PF in that it
      provides a local microenvironment in the lung that causes individual
      susceptibility. CTGF should be considered as a novel drug target and as a
      potential marker for identifying individuals at risk.

PMID- 15256389
TI  - Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma
      ControL study.
AB  - For most patients, asthma is not controlled as defined by guidelines; whether
      this is achievable has not been prospectively studied. A 1-year, randomized,
      stratified, double-blind, parallel-group study of 3,421 patients with
      uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in
      achieving two rigorous, composite, guideline-based measures of control: totally
      and well-controlled asthma. Treatment was stepped-up until total control was
      achieved (or maximum 500 microg corticosteroid twice a day). Significantly more
      patients in each stratum (previously corticosteroid-free, low- and moderate-dose
      corticosteroid users) achieved control with salmeterol/fluticasone than
      fluticasone. Total control was achieved across all strata: 520 (31%) versus 326
      (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%)
      at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became
      well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001)
      and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and
      at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone.
      Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone
      and fluticasone, respectively, were on the highest dose at the end of treatment.
      Exacerbation rates (0.07-0.27 per patient per year) and improvement in health
      status were significantly better with salmeterol/fluticasone. This study confirms
      that the goal of guideline-derived asthma control was achieved in a majority of
      the patients.

PMID- 15256390
TI  - Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary
      approach to diagnosis?
AB  - Current guidelines recommend that the clinician, radiologist, and pathologist
      work together to establish a diagnosis of idiopathic interstitial pneumonia.
      Three clinicians, two radiologists, and two pathologists reviewed 58 consecutive
      cases of suspected idiopathic interstitial pneumonia. Each participant was
      provided information in a sequential manner and was asked to record their
      diagnostic impression and level of confidence at each step. Interobserver
      agreement improved from the beginning to the end of the review. After the
      presentation of histopathologic information, radiologists changed their
      diagnostic impression more often than did clinicians. In general, as more
      information was provided the confidence level for a given diagnosis improved, and
      the diagnoses rendered with a high level of confidence were more likely congruent
      with the final pathologic consensus diagnosis. The final consensus pathologist
      diagnosis was idiopathic pulmonary fibrosis in 30 cases. Clinicians identified
      75% and radiologists identified 48% of these cases before presentation of the
      histopathologic information. Histopathologic information has the greatest impact
      on the final diagnosis, especially when the initial clinical/radiographic
      diagnosis is not idiopathic pulmonary fibrosis. We conclude that dynamic
      interactions between clinicians, radiologists, and pathologists improve
      interobserver agreement and diagnostic confidence.

PMID- 15256391
TI  - Particulate matter air pollution stimulates monocyte release from the bone
      marrow.
AB  - Particulate air pollution (PM(10)) stimulates alveolar macrophages (AMs) to
      release immature granulocytes from the bone marrow (BM) into the circulation.
      This study was designed to determine the effect of PM(10) (ambient EHC-93 or
      inert carbon [CC]) instillation exposure on the monocyte release from the BM and
      the role of AM in this response. Monocyte precursors were labeled in the BM of
      rabbits in vivo by an intravenous injection of 5'-bromo-2'-deoxyuridine, and the
      effects of PM(10) were determined by instillation either particles or
      supernatants of AM exposed to particles into the lungs. Instillation of EHC-93
      (500 microg/ml) or supernatants from AM incubated with EHC-93 (100 microg/ml)
      increased circulating band cell counts (p < 0.05) and shortened the transit time
      of monocytes through the BM (35.5 +/- 2.2 to 25.0 +/- 1.5 hours or 36.2 +/- 2.6
      to 25.7 +/- 1.8 hours, p < 0.05) compared with the control subject. CC (1%)
      instillation also shortened the monocyte BM transit time to 28.4 +/- 1.9 hours (p
      < 0.05), but supernatants of AM incubated with CC did not. We conclude that
      exposure to atmospheric PM(10) stimulates the production of mediators by AM, and
      these cytokines accelerate the monocyte release from the BM.

PMID- 15256392
TI  - Presence of activated mobile fibroblasts in bronchoalveolar lavage from patients
      with mild asthma.
AB  - Activated fibroblasts are suggested to be involved in the deposition of
      extracellular matrix in the formation of peribronchial fibrosis in asthma. We
      report the novel finding of activated elongated fibroblasts accompanied by
      elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12
      patients with mild asthma (= 42%), whereas no fibroblasts were observed in the
      control subjects without asthma (n = 17). The elongated fibroblasts migrated
      twice as far when compared with fibroblasts from corresponding bronchial biopsies
      from the same patients, accompanied by an induced expression of RhoA and Rac1,
      indicating that the increased expression of these proteins are linked to
      increased migratory capabilities. Moreover, the elongated fibroblasts had an
      elevated production of the proteoglycans biglycan, versican, perlecan, and
      decorin, which correlated to an active cytoplasm in these cells. Differential
      expression patterns between the two fibroblast groups in motility-regulating
      proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock
      protein 20, were identified by two-dimensional electrophoresis and mass
      spectrometry. These findings indicate the presence of activated and mobile
      fibroblasts accompanied by an induced inflammatory response outside the airway
      epithelium in patients with mild asthma, results that may play a role in
      formation of airway fibrosis.

PMID- 15256393
TI  - Diet and asthma.

PMID- 15256394
TI  - Early emphysema in patients with anorexia nervosa.
AB  - Postmortem studies of patients who died in the Warsaw Ghetto during World War II
      suggested that death from starvation was associated with pulmonary emphysema.
      This study re-examines this hypothesis in patients who are chronically
      malnourished because of anorexia nervosa. Age, smoking history, body mass index,
      and pulmonary function were measured in 21 subjects with anorexia nervosa and 16
      control subjects. Computed tomography (CT) scans were obtained from three regions
      of the lung (at the level of the aortic arch, the carina, and the posterior
      position of the eighth rib) using a multislice scanner. The CT measurements of
      lung density, emphysema, and surface area-to-volume ratio were obtained using the
      X-ray attenuation values. CT measurements of emphysema were greater in the group
      that was anorexic than in historical control subjects (p < 0.001). Furthermore,
      there were significant correlations between the body mass index and the CT
      measures of emphysema for all the patients and between diffusing capacity and the
      CT measurements in the patients who were anorexic. A multiple linear regression
      analysis showed the diffusing capacity was predicted best by the percentage of
      lung voxels within the large emphysematous changes category. These data
      demonstrate that emphysema-like changes are present in the lungs of patients who
      are chronically malnourished.

PMID- 15256395
TI  - Norepinephrine increases alveolar fluid reabsorption and Na,K-ATPase activity.
AB  - The purpose of this study was to determine whether alpha-adrenergic receptor
      agonists have a role in alveolar fluid reabsorption, via Na,K-ATPase, in the
      alveolar epithelium. Alveolar fluid reabsorption increased approximately twofold
      with increasing concentrations of norepinephrine (NE) as compared with control
      rats. Treatment with the nonselective alpha-adrenergic receptor agonist,
      octopamine, and the specific alpha(1) agonist, phenylephrine, increased alveolar
      fluid reabsorption by 54 and 40%, respectively, as compared with control. The
      specific alpha(1)-adrenergic receptor antagonist, prazosin, inhibited the
      stimulatory effects of NE by approximately 30%, whereas alpha(2)-adrenergic
      antagonist, yohimbine, did not prevent the stimulatory effects of NE. The
      administration of ouabain, Na,K-ATPase inhibitor, prevented the NE-mediated
      increase in alveolar fluid reabsorption. In parallel with these changes, NE
      increased Na,K-ATPase activity and protein abundance in alveolar epithelial type
      II cells via the alpha(1)- and beta-adrenergic receptor. We report here that NE
      increased alveolar fluid reabsorption via the activation of both alpha(1)- and
      beta-adrenergic receptors, but not alpha(2)-adrenergic receptors. These effects
      are due to increased activity and abundance of the Na,K-ATPase in the basolateral
      membrane of ATII cells.

PMID- 15256396
TI  - Systemic administration of serotonin 2A/2C agonist improves upper airway
      stability in Zucker rats.
AB  - The effects of [+/-]-2,5-dimethoxy-4-iodoaminophentamine, a serotonin(2A/2C)
      receptor agonist, on pharyngeal airflow mechanics were examined in isoflurane
      anesthetized lean and obese Zucker rats. The pharyngeal pressure associated with
      flow limitation, maximum inspiratory flow, oronasal resistance, genioglossus
      muscle activity, and arterial blood pressure (BP) were measured before and after
      the intravenous administration of the agonist. A robust activation of the
      genioglossus muscle in all lean and obese rats was associated with decreased
      upper airway (UA) collapsibility (p < 0.05), unchanged maximum flow, and
      increased oronasal resistance (p < 0.05) in both groups. The changes in UA
      mechanics and BP after the drug were similar in lean and obese rats. The
      serotonin agonist had no effect on UA mechanics in a group of paralyzed
      (pancuronium bromide) rats, despite similar elevations in BP. There was a smaller
      decrease (p < 0.05) in UA collapsibility that was also associated with increased
      upstream resistance when the drug was administered after bilateral hypoglossal
      nerve transection. We conclude that systemic administration of a serotonin(2A/2C)
      receptor agonist improves UA collapsibility predominantly, but not exclusively,
      via stimulation of the hypoglossal nerves and also increases upstream resistance,
      at least in part, through activation of nonhypoglossal motoneuronal pools
      innervating the UA muscles.

PMID- 15256397
TI  - Genetics of ultrasonographic carotid atherosclerosis.
AB  - The search for genes related to the cause of common complex disorders such as
      cardiovascular disease has been frustrating, partly because of the many factors
      known to contribute to cardiovascular disease and the potential "distance" of
      cardiovascular disease as a phenotype from genes and gene products. Linkage and
      association studies for phenotypes more proximal in the pathway from DNA sequence
      variation to overt clinical disease, such as ultrasound-defined carotid
      atherosclerosis, may potentially be more enlightening. Only one genetic variant
      previously reported to be associated with atherosclerosis or clinically evident
      cardiovascular disease, matrix metalloproteinase (MMP) 3, has shown consistently
      positive associations with carotid disease, although it has not been studied
      widely. Another, PON1 L55M, is weakly associated in subgroups only, and 2, ApoE
      and MTHFR, are equivocal. Genetic variants reported to be associated with
      clinical cardiovascular disease show weak or no relationship to carotid
      atherosclerosis. This may reflect the known inconsistency in associations of
      genetic variants with clinical cardiovascular disease itself. Alternatively,
      genetic determinants of ultrasound-defined carotid atherosclerosis may differ
      from those of clinically manifest cardiovascular disease and may require pursuit
      through large-scale genomic studies of carotid atherosclerosis as a distinct
      phenotype. Only 1 genetic variant, MMP 3, has shown consistently positive
      associations with ultrasonographic carotid disease, although it has not been
      studied widely. Another, PON1 L55 mol/L, is weakly associated in subgroups only.
      Genetic variants reported to be associated with clinical cardiovascular disease
      show weak or no relationship to carotid atherosclerosis.

PMID- 15256398
TI  - B-Myb represses vascular smooth muscle cell collagen gene expression and inhibits
      neointima formation after arterial injury.
AB  - OBJECTIVE: The function of B-Myb, a negative regulator of vascular smooth muscle
      cell (SMC) matrix gene transcription, was analyzed in the vasculature. METHODS
      AND RESULTS: Mice were generated in which the human B-myb gene was driven by the
      basal cytomegalovirus promoter, and 3 founders were identified. Mice appeared to
      develop normally, and human B-myb was expressed in the aortas. Total B-Myb levels
      were elevated in aortas of adult transgenic versus wild-type (WT) animals and
      varied inversely with alpha1(I) collagen mRNA expression. However, neonatal WT
      and transgenic aortas displayed comparable levels of alpha1(I) collagen mRNA,
      likely resulting from elevated levels of cyclin A, which ablated repression by B
      Myb. Aortic SMCs from adult transgenic animals displayed decreased alpha1(I)
      collagen mRNA levels. To examine the role of B-Myb after vascular injury, animals
      were subjected to femoral artery denudation, which induces SMC-rich lesion
      formation. A dramatic reduction in neointima formation and lumenal narrowing was
      observed in arteries of B-myb transgenic versus WT mice 4 weeks after injury.
      CONCLUSIONS: Data indicate that B-Myb, which inhibits matrix gene expression in
      the adult vessel wall, reduces neointima formation after vascular injury. To
      analyze B-Myb function in the vasculature, mice overexpressing B-myb were
      generated. Neonates displayed normal alpha1(I) collagen mRNA levels, whereas
      adults expressed decreased collagen mRNA in aortas and isolated vascular SMCs. On
      femoral artery denudation, neointima formation was dramatically reduced in B-myb
      transgenic mice.

PMID- 15256399
TI  - Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform
      expression in human arteries and veins.
AB  - OBJECTIVE: Impaired endothelial function, characterized by nitric oxide
      scavenging by increased superoxide production, is a hallmark of vascular disease
      states. However, molecular mechanisms regulating superoxide production in human
      blood vessels remain poorly defined. METHODS AND RESULTS: We compared endothelial
      function, vascular superoxide production, and the expression of NAD(P)H oxidase
      subunits in arteries and veins from patients undergoing coronary bypass surgery
      (n=86). Superoxide release was similar in arteries and veins. Inhibitor studies
      revealed that the NAD(P)H oxidase system was a quantitatively and proportionately
      greater source of superoxide in veins, whereas xanthine oxidase also contributed
      significantly to superoxide production in arteries. Moreover, NAD(P)H oxidase
      molecular composition differed in veins and arteries; veins expressed more nox2
      and p22phox, whereas the relative expression of nox4 was greater in arteries.
      However, there were strong correlations between p22phox and nox4 expression and
      between superoxide production, NAD(P)H oxidase activity, and endothelial function
      in arteries and veins from the same patient. CONCLUSIONS: In individuals with
      coronary artery disease, changes in vascular superoxide production, endothelial
      function, and NAD(P)H oxidase activity and expression are related in veins and
      arteries. These findings highlight the importance of systemic effects on the
      molecular regulation of the NAD(P)H oxidases in human vascular disease.
      Endothelial dysfunction is characterized by increased superoxide production.
      NAD(P)H oxidase activity and endothelial function are correlated in veins and
      arteries in coronary artery disease, suggesting regulation by systemic factors.
      The expression of the NAD(P)H oxidase subunits p22phox and nox4, although
      different in veins and arteries, are also correlated.

PMID- 15256400
TI  - Serial studies of mouse atherosclerosis by in vivo magnetic resonance imaging
      detect lesion regression after correction of dyslipidemia.
AB  - OBJECTIVE: We determined the effects of sustained normocholesterolemia on
      advanced mouse atherosclerosis and whether changes in plaque size and composition
      can be detected noninvasively by MRI. METHODS AND RESULTS: Aortic arch segments
      containing advanced lesions from apolipoprotein E-deficient (apoE-/-) mice (total
      cholesterol 1281+/-97 mg/dL) were transplanted into syngeneic wild-type (WT;
      111+/-11 mg/dL) or apoE-/- (702+/-74 mg/dL) recipient mice on chow diet. Mice
      underwent serial MRI at 3, 5, 7, and 9 weeks after transplantation. Compared with
      3 weeks, correction of dyslipidemia in WT recipient mice resulted in a monotonic
      decrease (regression) in arterial wall volume, whereas in apoE-/- recipient mice,
      further plaque progression was noted (P<0.05). MRI and histological measurements
      were closely correlated (R=0.937). The lesional content of macrophages decreased
      >90% (P<0.001), and smooth muscle cells increased in the WT recipient mice. In
      vivo T(1)-, T(2)-, and proton density-weighted images of the mouse thoracic aorta
      differentiated intraplaque lipid and collagen. CONCLUSIONS: Plaque changes can be
      noninvasively monitored by serial in vivo MRI of a mouse regression model. Our
      ability to image the thoracic aorta and perform in vivo plaque characterization
      will further enhance atherosclerosis studies. Serial in vivo MRI of mouse
      arterial plaque after correction of dyslipidemia revealed a monotonic decrease in
      lesion size (regression) and changes in lesion composition consistent with a
      stable plaque phenotype. Serial in vivo MRI will enhance studies of plaque
      regression in animal models in response to therapeutic interventions.

PMID- 15256401
TI  - CBS Genome Atlas Database: a dynamic storage for bioinformatic results and
      sequence data.
AB  - Currently, new bacterial genomes are being published on a monthly basis. With the
      growing amount of genome sequence data, there is a demand for a flexible and easy
      to-maintain structure for storing sequence data and results from bioinformatic
      analysis. More than 150 sequenced bacterial genomes are now available, and
      comparisons of properties for taxonomically similar organisms are not readily
      available to many biologists. In addition to the most basic information, such as
      AT content, chromosome length, tRNA count and rRNA count, a large number of more
      complex calculations are needed to perform detailed comparative genomics. DNA
      structural calculations like curvature and stacking energy, DNA compositions like
      base skews, oligo skews and repeats at the local and global level are just a few
      of the analysis that are presented on the CBS Genome Atlas Web page. Complex
      analysis, changing methods and frequent addition of new models are factors that
      require a dynamic database layout. Using basic tools like the GNU Make system,
      csh, Perl and MySQL, we have created a flexible database environment for storing
      and maintaining such results for a collection of complete microbial genomes.
      Currently, these results counts to more than 220 pieces of information. The
      backbone of this solution consists of a program package written in Perl, which
      enables administrators to synchronize and update the database content. The MySQL
      database has been connected to the CBS web-server via PHP4, to present a dynamic
      web content for users outside the center. This solution is tightly fitted to
      existing server infrastructure and the solutions proposed here can perhaps serve
      as a template for other research groups to solve database issues. AVAILABILITY: A
      web based user interface which is dynamically linked to the Genome Atlas Database
      can be accessed via www.cbs.dtu.dk/services/GenomeAtlas/. SUPPLEMENTARY
      INFORMATION: This paper has a supplemental information page which links to the
      examples presented: www.cbs.dtu.dk/services/GenomeAtlas/suppl/bioinfdatabase.

PMID- 15256402
TI  - Limited agreement among three global gene expression methods highlights the
      requirement for non-global validation.
AB  - MOTIVATION: DNA microarrays have revolutionized biological research, but their
      reliability and accuracy have not been extensively evaluated. Thorough testing of
      microarrays through comparison to dissimilar gene expression methods is necessary
      in order to determine their accuracy. RESULTS: We have systematically compared
      three global gene expression methods on all available histologically normal
      samples from five human organ types. The data included 25 Affymetrix high-density
      oligonucleotide array experiments, 23 expressed sequence tag based expression
      (EBE) experiments and 5 SAGE experiments. The reported gene-by-gene expression
      patterns showed a wide range of correlations between pairs of methods. This level
      of agreement was sufficient for accurate clustering of datasets from the same
      tissue and dissimilar methods, but highlights the need for thorough validation of
      individual gene expression measurements by alternate, non-global methods.
      Furthermore, analyses of mRNA abundance distributions indicate limitations in the
      EBE and SAGE methods at both high- and low-expression levels.

PMID- 15256403
TI  - DNAfan: a software tool for automated extraction and analysis of user-defined
      sequence regions.
AB  - SUMMARY: DNAfan (DNA Feature ANalyzer) is a tool combining sequence-filtering and
      pattern searching. DNAfan automatically extracts user-defined sets of sequence
      fragments from large sequence sets. Fragments are defined by annotated gene
      feature keys and co- or non-occurring patterns within the feature or close to it.
      A gene feature parser and a pattern-based filter tool localizes and extracts the
      specific subset of sequences. The selected sequence data can subsequently be
      retrieved for analyses or further processed with DNAfan to find the occurrence of
      specific patterns or structural motifs. DNAfan is a powerful tool for pattern
      analysis. Its filter features restricts the pattern search to a well-defined set
      of sequences, allowing drastic reduction in false positive hits. AVAILABILITY:
      http://bighost.ba.itb.cnr.it:8080/Framework.

PMID- 15256404
TI  - Gene selection using a two-level hierarchical Bayesian model.
AB  - SUMMARY: The fundamental problem of gene selection via cDNA data is to identify
      which genes are differentially expressed across different kinds of tissue samples
      (e.g. normal and cancer). cDNA data contain large number of variables (genes) and
      usually the sample size is relatively small so the selection process can be
      unstable. Therefore, models which incorporate sparsity in terms of variables
      (genes) are desirable for this kind of problem. This paper proposes a two-level
      hierarchical Bayesian model for variable selection which assumes a prior that
      favors sparseness. We adopt a Markov chain Monte Carlo (MCMC) based computation
      technique to simulate the parameters from the posteriors. The method is applied
      to leukemia data from a previous study and a published dataset on breast cancer.
      SUPPLEMENTARY INFORMATION: http://stat.tamu.edu/people/faculty/bmallick.html.

PMID- 15256405
TI  - GenePicker: replicate analysis of Affymetrix gene expression microarrays.
AB  - GenePicker allows efficient analysis of Affymetrix gene expression data performed
      in replicate, through definition of analysis schemes, data normalization, t
      test/ANOVA, Change-Fold Change-analysis and yields lists of differentially
      expressed genes with high confidence. Comparison of noise and signal analysis
      schemes allows determining a signal-to-noise ratio in a given experiment. Change
      Call, Fold Change and Signal mean ratios are used in the analysis. While each
      parameter alone yields gene lists that contain up to 30% false positives, the
      combination of these parameters nearly eliminates the false positives as verified
      by northern blotting, quantitative PCR in numerous independent experiments as
      well as by the analysis of spike-in data. AVAILABILITY: http://www.ifom
      firc.it/RESEARCH/Appl_Bioinfo/tools.html. SUPPLEMENTARY INFORMATION:
      http://www.ifom-firc.it/RESEARCH/Appl_Bioinfo/tools.html.

PMID- 15256406
TI  - Dimension reduction methods for microarrays with application to censored survival
      data.
AB  - MOTIVATION: Recent research has shown that gene expression profiles can
      potentially be used for predicting various clinical phenotypes, such as tumor
      class, drug response and survival time. While there has been extensive studies on
      tumor classification, there has been less emphasis on other phenotypic features,
      in particular, patient survival time or time to cancer recurrence, which are
      subject to right censoring. We consider in this paper an analysis of censored
      survival time based on microarray gene expression profiles. RESULTS: We propose a
      dimension reduction strategy, which combines principal components analysis and
      sliced inverse regression, to identify linear combinations of genes, that both
      account for the variability in the gene expression levels and preserve the
      phenotypic information. The extracted gene combinations are then employed as
      covariates in a predictive survival model formulation. We apply the proposed
      method to a large diffuse large-B-cell lymphoma dataset, which consists of 240
      patients and 7399 genes, and build a Cox proportional hazards model based on the
      derived gene expression components. The proposed method is shown to provide a
      good predictive performance for patient survival, as demonstrated by both the
      significant survival difference between the predicted risk groups and the
      receiver operator characteristics analysis. AVAILABILITY: R programs are
      available upon request from the authors. SUPPLEMENTARY INFORMATION:
      http://dna.ucdavis.edu/~hli/bioinfo-surv-supp.pdf.

PMID- 15256407
TI  - Mining HIV protease cleavage data using genetic programming with a sum-product
      function.
AB  - MOTIVATION: In order to design effective HIV inhibitors, studying and
      understanding the mechanism of HIV protease cleavage specification is critical.
      Various methods have been developed to explore the specificity of HIV protease
      cleavage activity. However, success in both extracting discriminant rules and
      maintaining high prediction accuracy is still challenging. The earlier study had
      employed genetic programming with a min-max scoring function to extract
      discriminant rules with success. However, the decision will finally be
      degenerated to one residue making further improvement of the prediction accuracy
      difficult. The challenge of revising the min-max scoring function so as to
      improve the prediction accuracy motivated this study. RESULTS: This paper has
      designed a new scoring function called a sum-product function for extracting HIV
      protease cleavage discriminant rules using genetic programming methods. The
      experiments show that the new scoring function is superior to the min-max scoring
      function. AVAILABILITY: The software package can be obtained by request to Dr
      Zheng Rong Yang.

PMID- 15256408
TI  - An optimized algorithm for flux estimation from isotopomer distribution in
      glucose metabolites.
AB  - MOTIVATION: Analysis of the conversion of (13)C glucose within the metabolic
      network allows the evaluation of the biochemical fluxes in interconnecting
      metabolic pathways. Such analyses require solving hundreds of equations with
      respect to individual isotopomer concentrations, and this assumes applying
      special software even for constructing the equations. The algorithm, proposed by
      others could be improved. METHOD: A C-code linked to the program written in
      Mathematica (Wolfram Research Inc.), constructs and solves differential equations
      for all isotopomer concentrations, using the general enzyme characteristics
      (K(m), equilibrium constant, etc.). This code uses innovative algorithm of
      determination for the isotopomers-products, thus essentially decreasing the
      computation time. Feasible metabolic fluxes are provided by the parameters of
      enzyme kinetics found from the data fitting. RESULTS: The software effectively
      evaluates metabolic fluxes based on the measured isotopomer distribution, as was
      illustrated by the analysis of glycolysis and pentose phosphate cycle. The
      mechanism of transketolase and transaldolase catalysis was shown to induce a
      specific kind of isotopomer re-distribution, which, despite the significance of
      its effect, usually is not taken into account. AVAILABILITY: The software could
      be freely downloaded from the site: http://bq.ub.es/bioqint/label_distribution/.

PMID- 15256409
TI  - CRH_Server: an online comparative and radiation hybrid mapping server for the
      canine genome.
AB  - CRH_Server is an on line Comparative and Radiation Hybrid mapping Server
      dedicated to canine genomics. CRH_Server allows users to compute their own RH
      data using the current canine RH map, and allows comparative dog/human mapping
      analyses. Finally, it suggests multiple options for storage and queries of the
      dog RH database. AVAILABILITY: http://idefix.univ-rennes1.fr:8080/Dogs/rh
      server.html. SUPPLEMENTARY INFORMATION: All information is available at
      http://idefix.univ-rennes1.fr:8080/Dogs/help_rh-server.html.

PMID- 15256410
TI  - A software program combining sequence motif searches with keywords for finding
      repeats containing DNA sequences.
AB  - MOTIVATION: One of the most interesting features of genomes (both coding and non
      coding regions) is the presence of relatively short tandemly repeated DNA
      sequences known as tandem repeats (TRs). We developed a new PC-based stand-alone
      software analysis program, combining sequence motif searches with keywords such
      as organs, tissues, cell lines or development stages for finding exact, inexact
      and compound, TRs. Tandem Repeats Analyzer 1.5 (TRA) has several advanced repeat
      search parameters/options over other repeat finder programs as it does not only
      accept GenBank, FASTA and expressed sequence tag (EST) sequence files but also
      does analysis of multifiles with multisequences. Advanced user-defined
      parameters/options let the researchers use different motif lengths search
      criteria for varying motif lengths simultaneously. The outputs show statistical
      results to be evaluated by the user. The discovery of TRs in ESTs could be useful
      for both gene mapping and association studies and discovering TRs located in
      coding regions of important genes that are expressed under various conditions of
      environment, stress, organ, tissue and development stage. RESULTS: In this paper,
      we demonstrated applications of TRA using 175 899 ESTs sequences for three
      Arabidopsis spp. downloaded from GenBank. The EST-SSRs/ESTs ratios were found
      43.1%, 15.3% and 2.34% in A.lyrata, A.thaliana and A.halleri, respectively.
      Analysis revealed that organs, tissues and development stages possessed different
      amounts of repeats and repeat compositions. This indicated that the distribution
      of TRs among the tissues or organs may not be random differing from the
      untranscribed repeats found in genomes. AVAILABILITY: The program can be obtained
      free by anonymous FTP from ftp.akdeniz.edu.tr/Araclar/TRA.

PMID- 15256411
TI  - Extracting gene pathway relations using a hybrid grammar: the Arizona Relation
      Parser.
AB  - MOTIVATION: Text-mining research in the biomedical domain has been motivated by
      the rapid growth of new research findings. Improving the accessibility of
      findings has potential to speed hypothesis generation. RESULTS: We present the
      Arizona Relation Parser that differs from other parsers in its use of a broad
      coverage syntax-semantic hybrid grammar. While syntax grammars have generally
      been tested over more documents, semantic grammars have outperformed them in
      precision and recall. We combined access to syntax and semantic information from
      a single grammar. The parser was trained using 40 PubMed abstracts and then
      tested using 100 unseen abstracts, half for precision and half for recall. Expert
      evaluation showed that the parser extracted biologically relevant relations with
      89% precision. Recall of expert identified relations with semantic filtering was
      35 and 61% before semantic filtering. Such results approach the higher-performing
      semantic parsers. However, the AZ parser was tested over a greater variety of
      writing styles and semantic content. AVAILABILITY: Relations extracted from over
      600 000 PubMed abstracts are available for retrieval and visualization at
      http://econport.arizona.edu:8080/NetVis/index.html.

PMID- 15256412
TI  - Reducing storage requirements for biological sequence comparison.
AB  - MOTIVATION: Comparison of nucleic acid and protein sequences is a fundamental
      tool of modern bioinformatics. A dominant method of such string matching is the
      'seed-and-extend' approach, in which occurrences of short subsequences called
      'seeds' are used to search for potentially longer matches in a large database of
      sequences. Each such potential match is then checked to see if it extends beyond
      the seed. To be effective, the seed-and-extend approach needs to catalogue seeds
      from virtually every substring in the database of search strings. Projects such
      as mammalian genome assemblies and large-scale protein matching, however, have
      such large sequence databases that the resulting list of seeds cannot be stored
      in RAM on a single computer. This significantly slows the matching process.
      RESULTS: We present a simple and elegant method in which only a small fraction of
      seeds, called 'minimizers', needs to be stored. Using minimizers can speed up
      string-matching computations by a large factor while missing only a small
      fraction of the matches found using all seeds.

PMID- 15256413
TI  - Preferred in vivo ubiquitination sites.
AB  - MOTIVATION: The conjugation of ubiquitin to target molecules involves several
      enzymatic steps. Little is known about the specificity of ubiquitination. How E3
      ligases select their substrate and which lysines are targeted for ubiquitin
      conjugation is largely an enigma. The object of this study is to identify
      preferred ubiquitination sites. Genetic approaches to study this question have
      proven difficult, because of the redundancy of ligases and the lack of strictly
      required motifs. However, a better understanding of acceptor site selection could
      help to predict ubiquitination sites and clarify yet unsolved structure-function
      relationships of the transfer reaction. RESULTS: In an effort to define
      preferences for ubiquitination, we systematically analyzed structure and sequence
      of 135 known ubiquitination sites in 95 proteins in Saccharomyces cerevisiae. The
      results show clear structural preferences for ubiquitin ligation to target
      proteins, and compartment-specific amino acid patterns in close proximity to the
      modified side chain. SUPPLEMENTARY INFORMATION:
      http://www.people.fas.harvard.edu/~catic.

PMID- 15256414
TI  - Interactive gene-order comparison for multiple small genomes.
AB  - The Genome Organization Analysis Tool (GOAT) is a program that performs
      comparative sequence analysis on ordered gene lists from annotated genomes,
      provides visual and tabular output, and provides means of accessing and analyzing
      related gene sequence data, for the purpose of comparing genome organization at
      the gene-order level. GOAT can be used to compare any two or more genomes or
      chromosomes on demand, or configured to provide access to precomputed comparisons
      of a specific group of genome sequences. AVAILABILITY: Demonstration web server
      and software download, subject to the Virginia Tech Noncommercial License are
      available at http://gaia.biotech.vt.edu/goat/. SUPPLEMENTARY INFORMATION:
      Updates, installation and configuration information are available at
      http://gaia.biotech.vt.edu/goat.

PMID- 15256415
TI  - A graph-theoretic approach to testing associations between disparate sources of
      functional genomics data.
AB  - MOTIVATION: The last few years have seen the advent of high-throughput
      technologies to analyze various properties of the transcriptome and proteome of
      several organisms. The congruency of these different data sources, or lack
      thereof, can shed light on the mechanisms that govern cellular function. A
      central challenge for bioinformatics research is to develop a unified framework
      for combining the multiple sources of functional genomics information and testing
      associations between them, thus obtaining a robust and integrated view of the
      underlying biology. RESULTS: We present a graph-theoretic approach to test the
      significance of the association between multiple disparate sources of functional
      genomics data by proposing two statistical tests, namely edge permutation and
      node label permutation tests. We demonstrate the use of the proposed tests by
      finding significant association between a Gene Ontology-derived predictome and
      data obtained from mRNA expression and phenotypic experiments for Saccharomyces
      cerevisiae. Moreover, we employ the graph-theoretic framework to recast a
      surprising discrepancy presented elsewhere between gene expression and knockout
      phenotype, using expression data from a different set of experiments.
      AVAILABILITY: An R software package, GraphAT, containing the data and statistical
      procedures is available from Bioconductor: http://www.bioconductor.org.

PMID- 15256416
TI  - Importing MAGE-ML format microarray data into BioConductor.
AB  - The microarray gene expression markup language (MAGE-ML) is a widely used XML
      (eXtensible Markup Language) standard for describing and exchanging information
      about microarray experiments. It can describe microarray designs, microarray
      experiment designs, gene expression data and data analysis results. We describe
      RMAGEML, a new Bioconductor package that provides a link between cDNA microarray
      data stored in MAGE-ML format and the Bioconductor framework for preprocessing,
      visualization and analysis of microarray experiments. AVAILABILITY:
      http://www.bioconductor.org. Open Source.

PMID- 15256417
TI  - Bullying among doctors in training: cross sectional questionnaire survey.

PMID- 15256418
TI  - Neurological sequelae in twins born after assisted conception: controlled
      national cohort study.
AB  - OBJECTIVE: To compare neurological sequelae in twins born after assisted
      conception with singletons after assisted conception and naturally conceived
      twins and to assess neurological sequelae in children conceived after in vitro
      fertilisation (IVF) compared with intracytoplasmic sperm injection (ICSI).
      DESIGN: Controlled, national register based, cohort study. PARTICIPANTS: Twins (n
      = 3393) and singletons (n = 5130) conceived by using assisted reproductive
      technologies and naturally conceived twins (n = 10 239) born in Denmark between
      1995 and 2000. The children's age at time of follow up was 2-7 years. DATA
      SOURCES: Children were identified by cross linkage of the national medical birth
      registry and the national registry for in vitro fertilisation. Neurological and
      psychiatric diagnoses were retrieved from the national patients' registry and the
      Danish psychiatric central registry. MAIN OUTCOME MEASURES: Neurological
      sequelae, defined as cerebral palsy, mental retardation, severe mental
      developmental disturbances, and retarded psychomotor development. Further we made
      separate analyses on the specific cerebral palsy diagnosis. RESULTS: The crude
      prevalence rates per 1000 of neurological sequelae in twins and singletons after
      assisted conception and in naturally conceived twins were 8.8, 8.2, and 9.6, and
      of cerebral palsy 3.2, 2.5, and 4.0, respectively. In twins after assisted
      conception compared with control twins, the odds ratios of neurological sequelae
      and specifically of cerebral palsy, adjusted for child sex and year of birth,
      were 0.9 (95% confidence interval 0.6 to 1.4) and 0.8 (0.4 to 1.6), respectively.
      The corresponding odds ratios for twins after assisted conception compared with
      singletons after assisted conception were 1.1 (0.7 to 1.7) for neurological
      sequelae and 1.3 (0.6 to 2.9) for cerebral palsy. The odds ratio of neurological
      sequelae in children conceived by ICSI was 0.9 (0.5 to 1.7) nu children conceived
      by IVF. CONCLUSIONS: Twins from assisted conception have a similar risk of
      neurological sequelae as their naturally conceived peers and singletons from
      assisted conception. Children born after ICSI have the same risk of neurological
      sequelae as children born after IVF.

PMID- 15256419
TI  - The long term clinical course of acute deep vein thrombosis of the arm:
      prospective cohort study.

PMID- 15256420
TI  - Variable sensitivity of FLT3 activation loop mutations to the small molecule
      tyrosine kinase inhibitor MLN518.
AB  - FLT3 is constitutively activated by internal tandem duplications (ITDs) in the
      juxtamembrane domain or by activation loop mutations in acute myeloid leukemia
      (AML). We tested the sensitivity of 8 activation loop mutations to the small
      molecule FLT3 inhibitor, MLN518. Each FLT3 activation loop mutant, including
      D835Y, D835A, D835E, D835H, D835N, D835V, D835del, and I836del, transformed Ba/F3
      cells to factor-independent proliferation and had constitutive tyrosine kinase
      activation, as assessed by FLT3 autophosphorylation and activation of downstream
      effectors, including STAT5 and ERK. MLN518 inhibited FLT3 autophosphorylation and
      phosphorylation of STAT5 and ERK in FLT3-ITD-transformed Ba/F3 cells with an
      IC(50) (50% inhibition of cell viability) of approximately 500 nM. However, there
      was a broad spectrum of sensitivity among the 8 activation loop mutants, with
      IC(50) ranging from approximately 500 nM to more than 10 microM for the
      inhibition of phosphorylation of FLT3, STAT5, and ERK. The relative sensitivity
      of the mutants to MLN518 in biochemical assays correlated with the cellular
      IC(50) for cytokine-independent proliferation of FLT3-transformed Ba/F3 cells in
      the presence of MLN518. Thus, certain activation loop mutations in FLT3
      simultaneously confer resistance to small molecule inhibitors. These findings
      have implications for the evaluation of responses in clinical trials with FLT3
      inhibitors and provide a strategy to screen for compounds that can overcome
      resistance.

PMID- 15256421
TI  - Human fetal, cord blood, and adult lymphocyte progenitors have similar potential
      for generating B cells with a diverse immunoglobulin repertoire.
AB  - Several characteristics of the immunoglobulin (Ig) repertoire in fetuses and
      adults set them apart from each other. Functionally, this translates into
      differences in the affinity and effectiveness of the humoral immune response
      between adults and the very young. At least 2 possibilities could explain these
      differences: (1) fetal and adult lymphocyte progenitors differ significantly in
      their potential to form a diverse repertoire, and (2) factors extrinsic to the
      immunoglobulin locus are more influential to the character of the repertoire. To
      address this we used nonobese diabetic-severe combined immunodeficient-beta(2)
      microglobulin knockout (NOD/SCID/beta(2)m(-/-)) mice reconstituted with human B
      cell progenitors to compare the immunoglobulin repertoire potential of human
      fetal, cord blood, and adult sources. We found nearly identical VH and JH gene
      segment use and only modest differences in the third complementarity determining
      region of the immunoglobulin heavy chain (HCDR3). We conclude that the repertoire
      potential is remarkably similar regardless of the age of the individual from
      which progenitors are derived. Age-related differences in the immunoglobulin
      repertoire and variance of B-cell responses to immunization appear to arise from
      selection rather than from changes in recombination of the immunoglobulin locus
      itself. From the standpoint of the Ig repertoire, an immune system reconstituted
      from fetal or neonatal stem cells would likely be as diverse as one generated
      from adult bone marrow.

PMID- 15256422
TI  - Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based
      oncogenic protein kinase inhibitor: implications for CML.
AB  - The deregulated, oncogenic tyrosine kinase Bcr-Abl causes chronic myeloid
      leukemia (CML). Imatinib mesylate (Gleevec, STI571), a Bcr-Abl kinase inhibitor,
      selectively inhibits proliferation and promotes apoptosis of CML cells. Despite
      the success of imatinib mesylate in the treatment of CML, resistance is observed,
      particularly in advanced disease. The most common imatinib mesylate resistance
      mechanism involves Bcr-Abl kinase domain mutations that impart varying degrees of
      drug insensitivity. AP23464, a potent adenosine 5'-triphosphate (ATP)-based
      inhibitor of Src and Abl kinases, displays antiproliferative activity against a
      human CML cell line and Bcr-Abl-transduced Ba/F3 cells (IC(50) = 14 nM; imatinib
      mesylate IC(50) = 350 nM). AP23464 ablates Bcr-Abl tyrosine phosphorylation,
      blocks cell cycle progression, and promotes apoptosis of Bcr-Abl-expressing
      cells. Biochemical assays with purified glutathione S transferase (GST)-Abl
      kinase domain confirmed that AP23464 directly inhibits Abl activity. Importantly,
      the low nanomolar cellular and biochemical inhibitory properties of AP23464
      extend to frequently observed imatinib mesylate-resistant Bcr-Abl mutants,
      including nucleotide binding P-loop mutants Q252H, Y253F, E255K, C-terminal loop
      mutant M351T, and activation loop mutant H396P. AP23464 was ineffective against
      mutant T315I, an imatinib mesylate contact residue. The potency of AP23464
      against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode
      relative to imatinib mesylate warrant further investigation of AP23464 for the
      treatment of CML.

PMID- 15256423
TI  - Better outcome of adult acute lymphoblastic leukemia after early genoidentical
      allogeneic bone marrow transplantation (BMT) than after late high-dose therapy
      and autologous BMT: a GOELAMS trial.
AB  - Various transplantation strategies have been designed to improve the poor
      prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The
      GOELAL02 trial evaluated the impact of early allogeneic bone marrow
      transplantation (alloBMT) or delayed unpurged autologous stem cell
      transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)
      matched sibling donor or who were older than 50 years. Inclusion criteria
      included at least one of the following: age older than 35 years; non-T-ALL;
      leukocytosis greater than 30 x 10(9)/L; t(9;22), t(4;11), or t(1; 19); or failure
      to achieve complete remission (CR) after one induction course. Among 198
      patients, the median age was 33 years. The CR rate was 80% with vincristine,
      idarubicine, L-asparaginase, and randomized intravenous injection or oral
      steroids (P = nonsignificant [ns]). AlloBMT was performed after 2 consolidation
      courses while ASCT was delayed after 1 additional reinduction. Intensified
      conditioning regimen before transplantation included etoposide, cyclophosphamide,
      and total body irradiation (TBI). Median follow-up was 5.1 years. The median
      overall survival (OS) was 29 months, with a 6-year OS of 41%. On an intent-to
      treat analysis for patients younger than 50 years, alloBMT significantly improved
      the 6-year OS (75% versus 40% after ASCT; P = .0027). Randomized interferon-alpha
      maintenance had no effect on relapse or survival after ASCT. In conclusion, the
      outcome of adult ALL is better after early alloBMT than after delayed ASCT.

PMID- 15256424
TI  - Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand
      display technology.
AB  - Gene therapy for a wide variety of disorders would be greatly enhanced by the
      development of vectors that could be targeted for gene delivery to specific
      populations of cells. We describe here high-efficiency targeted transduction
      based on a novel targeting strategy that exploits the ability of retroviruses to
      incorporate host cell proteins into the surface of the viral particle as they bud
      through the plasma membrane. Ecotropic retroviral particles produced in cells
      engineered to express the membrane-bound form of stem cell factor (mbSCF)
      transduce both human cell lines and primary cells with high efficiency in a
      strictly c-kit (SCF receptor)-dependent fashion. The availability of efficient
      targeted vectors provides a platform for the development of a new generation of
      therapies using in vivo gene delivery.

PMID- 15256425
TI  - The Fanconi anemia core complex associates with chromatin during S phase.
AB  - Fanconi anemia (FA) is an autosomal recessive disease marked by bone marrow
      failure, birth defects, and cancer. The FA proteins FANCA, FANCC, FANCE, FANCF,
      FANCG, and FANCL participate in a core complex. We previously have shown that
      several members of this complex bind to chromatin until mitosis and that this
      binding increases after DNA damage. The purpose of the present study was to
      determine the dynamics of complex movement between cytoplasm and nuclear
      compartments. Fluorescent-tagged versions of FANCA, FANCC, and FANCG colocalize
      in cytoplasm and nucleus, chiefly in chromatin. At the G1-S border, the FA core
      complex exists as foci on chromatin, progressively diffusing and migrating to the
      nuclear periphery and becoming completely excluded from condensed chromosomes by
      mitosis. Chromatin fiber analysis shows FA proteins diffusely staining along
      chromatin fibers during G1-S and S phase. Treatment with the DNA cross-linker
      mitomycin C results in a diffusion of foci and increased binding of complex
      proteins to chromatin, as well as diffuse and increased complex binding to
      chromatin fibers. These data are consistent with the idea that the FA proteins
      function at the level of chromatin during S phase to regulate and maintain
      genomic stability.

PMID- 15256426
TI  - Combination of retinoic acid and tumor necrosis factor overcomes the maturation
      block in a variety of retinoic acid-resistant acute promyelocytic leukemia cells.
AB  - Retinoic acid (RA) overcomes the maturation block in t(15:17) acute promyelocytic
      leukemia (APL), leading to granulocytic differentiation. Patients receiving RA
      alone invariably develop RA resistance. RA-resistant cells can serve as useful
      models for the development of treatments for both APL and other leukemias.
      Previously, we showed that RA and tumor necrosis factor (TNF) promote monocytic
      differentiation of the APL cell line NB4 and U937 monoblastic cells. Here, we
      report that combining TNF with RA leads to maturation of several RA-resistant APL
      cells along a monocytic pathway, whereas UF-1, a patient-derived RA-resistant
      cell line, showed characteristics of granulocytic differentiation. We found
      distinct differences in gene regulation between UF-1 cells and cells showing
      monocytic differentiation. Although IRF-7 was up-regulated by TNF and RA in all
      cells tested, expression of c-jun and PU.1 correlated with monocytic
      differentiation. Furthermore, synergistic induction of PU.1 DNA binding and
      macrophage colony-stimulating factor receptor (m-CSF-1R) mRNA was observed only
      in cells differentiating into monocytes. Using neutralizing antibodies against m
      CSF-1R or its ligand, we found that inhibiting this pathway strongly reduced CD14
      expression in response to RA and TNF, suggesting that this pathway is essential
      for their synergy in RA-resistant leukemia cells.

PMID- 15256427
TI  - Noninvasive measurement and imaging of liver iron concentrations using proton
      magnetic resonance.
AB  - Measurement of liver iron concentration (LIC) is necessary for a range of iron
      loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell
      disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of
      needle biopsy specimens is the most common accepted method of measurement. This
      study presents a readily available noninvasive method of measuring and imaging
      LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver
      proton transverse relaxation rates (R2) were measured for 105 humans. A value for
      the LIC for each subject was obtained by chemical assay of a needle biopsy
      specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were
      found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg
      Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced
      from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue.
      Proton transverse relaxation rates in aqueous paramagnetic solutions were also
      measured on each magnetic resonance imaging unit to ensure instrument-independent
      results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms
      on 13 different magnetic resonance imaging units using the method yielded a
      coefficient of variation of 2.1%.

PMID- 15256428
TI  - Atypical marginal zone hyperplasia of mucosa-associated lymphoid tissue: a
      reactive condition of childhood showing immunoglobulin lambda light-chain
      restriction.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas usually arise at sites of
      acquired MALT and are uncommon in native MALT (eg, Peyer patches and tonsil).
      Malignancy in these low-grade lymphomas is often inferred by immunoglobulin light
      chain restriction and expression of CD43; molecular genetic evidence is sought
      only if these are in doubt. We report 6 cases (4 tonsils, 2 appendixes) of
      marginal zone (MZ) hyperplasia in children aged 3 to 11 years that, despite
      histologic and immunophenotypic features indicative of lymphoma, were polyclonal
      by molecular analysis. No lymphoma-directed therapy was given and patients remain
      alive and well (5 cases, median follow-up 35.3 months). The involved tonsil and
      appendix showed florid MZ hyperplasia with prominent intraepithelial B cells
      (IEBCs). The MZ B cells and IEBCs showed a high-proliferation fraction and a
      CD20(+), CD21(+), CD27(-), immunoglobulin (Ig) superfamily receptor translocation
      associated 1-positive (IRTA-1(+)), CD43(+), multiple myeloma oncogene 1 (MUM-1),
      IgM(+)D(+) phenotype. Polymerase chain reaction (PCR), cloning, and sequencing of
      rearranged IgH and Iglambda genes (whole tissue sections [6 cases];
      microdissected cells [2 cases]) showed that the MZ B cells and IEBCs were
      polyclonal and the IgH genes nonmutated. In contrast, MZ (intraepithelial) B
      cells of 6 control tonsils had a similar immunophenotype, except for expression
      of CD27 and polytypic light chains, whereas molecular studies showed that they
      were polyclonal with mutated Ig genes.

PMID- 15256429
TI  - Real-time quantitative PCR analysis can be used as a primary screen to identify
      patients with CML treated with imatinib who have BCR-ABL kinase domain mutations.
AB  - Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid
      leukemia (CML) are the main mechanism of acquired resistance. The early detection
      of mutations should provide clinical benefit by allowing early intervention.
      Quantitative polymerase chain reaction (RQ-PCR) results of BCR-ABL mRNA were
      correlated with mutation analysis in 214 patients treated with imatinib. We
      determined whether there was a difference in the incidence of mutations between
      the patients with a more than 2-fold rise in BCR-ABL and patients with stable or
      decreasing levels. Of the 56 patients with a more than 2-fold rise, 34 (61%) had
      detectable mutations (median rise, 3.0-fold; 25th-75th percentiles, 2.3-5.2). In
      31 (91%) of these 34 patients, the mutation was present at the time of the rise
      and became detectable within 3 months in the remaining patients. Only 1 (0.6%) of
      158 patients with stable or decreasing BCR-ABL levels had a detectable mutation,
      P less than .0001. Thus, a more than 2-fold rise identified 34 (97%) of 35
      patients with a mutation. We conclude that a rise in BCR-ABL of more than 2-fold
      can be used as a primary indicator to test patients for BCR-ABL kinase domain
      mutations.

PMID- 15256430
TI  - A spectrum of biophysical interaction modes between T cells and different antigen
      presenting cells during priming in 3-D collagen and in vivo.
AB  - For activation T cells engage antigen-presenting cells (APCs) in lymphatic
      tissues. The contact duration and kinetics (static versus dynamic) vary
      considerably in different model systems; however, it is unclear whether T cells,
      APCs, or the environment are responsible for the observed discrepancies. Using 3
      D collagen matrices as structural scaffold, we directly compared the kinetics of
      T-cell engagement and activation by functionally major APC types, ie, dendritic
      cells (DCs) and resting or activated B cells. Resting B cells engaged T cells in
      long-lived (several hours), adhesive, and leukocyte function-associated antigen-1
      (LFA-1)-dependent conjugates in 3-D collagen as well as in intact lymph nodes in
      vivo. DCs and preactivated B cells, however, supported predominantly dynamic,
      short-lived (minutes), and sequential contacts to T cells that were dependent on
      high cytoskeletal activity of the APCs but could not be inhibited by anti-LFA-1
      treatment. Naive T cells were most strongly activated by DCs and activated B
      cells, whereas resting B cells were 100-fold less efficient to induce T-cell
      proliferation. Thus, in the same 3-D environment, naive T cells respond with a
      spectrum of different interaction modes dependent on the type and activation
      state of the APCs. Thereby, more dynamic interaction kinetics is positively
      correlated with higher T-cell priming efficiency.

PMID- 15256431
TI  - Transforming growth factor beta receptor type II inactivation promotes the
      establishment and progression of colon cancer.
AB  - Deregulation of members of the transforming growth factor (TGF)-beta signaling
      pathway occurs often in colon cancers and is believed to affect the formation of
      primary colon cancer. Mutational inactivation of TGFBR2 is the most common
      genetic event affecting the TGF-beta signaling pathway and occurs in
      approximately 20-30% of all colon cancers. By mating Fabpl(4xat-132) Cre mice
      with Tgfbr2(flx/flx) mice, we have generated a mouse model that is null for
      Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the
      effect of loss of TGF-beta signaling in vivo on colon cancer formation induced by
      azoxymethane (AOM). We have observed a significant increase in the number of AOM
      induced adenomas and adenocarcinomas in the Fabpl(4xat-132) Cre Tgfbr2(flx/flx)
      mice compared with Tgfbr2(flx/flx) mice, which have intact TGF-beta receptor type
      II (TGFBR2) in the colon epithelium, and we have found increased proliferation in
      the neoplasms occurring in the Fabpl(4xat-132) Cre Tgfbr2(flx/flx) mice. These
      results implicate the loss of TGF-beta-mediated growth inhibition as one of the
      in vivo mechanisms through which TGFBR2 inactivation contributes to colon cancer
      formation. Thus, we have demonstrated that loss of TGFBR2 in colon epithelial
      cells promotes the establishment and progression of AOM-induced colon neoplasms,
      providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor
      gene in the colon.

PMID- 15256432
TI  - CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion,
      migration, and survival of human prostate cancer cells.
AB  - Chemokines and their receptors might be involved in the selection of specific
      organs by metastatic cancer cells. For instance, the CXCR4-SDF-1alpha pair
      regulates adhesion and migration of breast as well as prostate cancer cells to
      metastatic sites. In this study, we present the first evidence for the expression
      of CX3CR1--the specific receptor for the chemokine fractalkine--by human prostate
      cancer cells, whereas human bone marrow endothelial cells and differentiated
      osteoblasts express fractalkine. The adhesion of prostate cancer cells to human
      bone marrow endothelial cells in flow conditions is significantly reduced by a
      neutralizing antibody against fractalkine, and they migrate toward a medium
      conditioned by osteoblasts, which secrete the soluble form of the chemokine.
      Finally, fractalkine activates the PI3K/Akt survival pathway in human prostate
      cancer cells.

PMID- 15256433
TI  - Impaired angiogenesis, delayed wound healing and retarded tumor growth in
      perlecan heparan sulfate-deficient mice.
AB  - Perlecan, a modular proteoglycan carrying primary heparan sulfate (HS) side
      chains, is a major component of blood vessel basement membranes. It sequesters
      growth factors such as fibroblast growth factor 2 (FGF-2) and regulates the
      ligand-receptor interactions on the cell surface, and thus it has been implicated
      in the control of angiogenesis. Both stimulatory and inhibitory effects of
      perlecan on FGF-2 signaling have been reported. To understand the in vivo
      function of HS carried by perlecan, the perlecan gene heparan sulfate
      proteoglycan 2 (Hspg2) was mutated in mouse by gene targeting. The HS at the
      NH(2) terminus of perlecan was removed while the core protein remained intact.
      Perlecan HS-deficient (Hspg2(Delta3/Delta3)) mice survived embryonic development
      and were apparently healthy as adults. However, mutant mice exhibited
      significantly delayed wound healing, retarded FGF-2-induced tumor growth, and
      defective angiogenesis. In the mouse corneal angiogenesis model, FGF-2-induced
      neovascularization was significantly impaired in Hspg2(Delta3/Delta3) mutant
      mice. Our results suggest that HS in perlecan positively regulates the
      angiogenesis in vivo.

PMID- 15256434
TI  - Increased expression of metallothionein is associated with irinotecan resistance
      in gastric cancer.
AB  - To gain insight into clinically relevant mechanisms of irinotecan resistance, we
      undertook oligonucleotide microarray analyses on paired malignant effusion
      samples obtained from eight gastric cancer patients treated with weekly
      irinotecan. Pretreatment and posttreatment (48 h) effusion samples were obtained
      for each patient, and the change in expression profile was compared between
      clinical responders and nonresponders. When differences in the expression of
      genes were examined using SAM (Significance Analysis of Microarrays) software,
      five isoforms of the metallothionein family were identified to have significantly
      higher signal log ratios in five nonresponders, compared with three responders.
      Compared with control cells, metallothionein 1X (MT1X)-transfected AGS cells
      showed a 1.4-fold higher irinotecan IC(50) by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and tended to form more colonies. These
      findings collectively suggest that irinotecan-induced up-regulation of
      metallothionein might be associated with irinotecan resistance in patients with
      gastric cancer, although it remains to be confirmed in a larger data set.

PMID- 15256435
TI  - A constitutively active dioxin/aryl hydrocarbon receptor promotes
      hepatocarcinogenesis in mice.
AB  - The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated
      transcription factor regulating transcription of a battery of genes encoding
      enzymes involved in drug metabolism. Known ligands include polycyclic aromatic
      hydrocarbons, certain polychlorinated biphenyls, and the polyhalogenated dioxins
      including 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both polyhalogenated biphenyls and
      2,3,7,8-tetrachlorodibenzo-p-dioxin are potent promoters of rodent
      hepatocarcinogenesis in two-stage initiation-promotion experiments. Although
      several lines of evidence indicate the involvement of the AhR in toxic effects
      mediated by polyhalogenated biphenyls and dioxins, its involvement in tumor
      promotion has not been unequivocally proven. In the present study, a transgenic
      mouse line expressing a constitutively active AhR (CA-AhR) has been used to
      investigate the role of the AhR in hepatocarcinogenesis. Male AhR wild-type and
      CA-AhR-transgenic B6C3F1-mice were treated with a single injection of the
      hepatocarcinogen N-nitrosodiethylamine at 6 weeks of age and were subsequently
      kept untreated on control diet. Thirty five weeks after carcinogen treatment,
      mice were sacrificed, and the prevalence and multiplicity of liver tumors were
      determined. Whereas only 1 small liver tumor was observed in 15 AhR-wild-type
      mice, 19 tumors (two >1 cm in diameter) were present in 18 CA-AhR-transgenic
      mice. This result demonstrates the oncogenic potential of the activated AhR and
      implicates an important role of the receptor in promotion of
      hepatocarcinogenesis. A microarray-based gene expression-profiling analysis
      revealed down-regulation in the liver of CA-AhR-transgenic mice of a cluster of
      genes encoding heat shock proteins, including GRP78/BiP, Herp1, Hsp90, DnaJ
      (Hsp40) homologue B1, and Hsp105, which are important for protein folding and
      quality control.

PMID- 15256436
TI  - Hypoxia-induced vascular endothelial growth factor transcription and protection
      from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells.
AB  - The alpha6beta1 integrin has been implicated in breast carcinoma progression, but
      the mechanisms involved remain elusive. MDA-MB-435 cells engineered to be
      deficient in alpha6beta1 expression form primary tumors that are highly apoptotic
      and unable to metastasize, although they exhibit no increased apoptosis in vitro
      under standard culture conditions. Based on the hypothesis that alpha6beta1 is
      necessary for the survival of these cells in the tumor microenvironment, we
      report here that hypoxia protects these cells from apoptosis induced by serum
      deprivation and that hypoxia-mediated protection requires alpha6beta1 expression.
      We investigated the influence of alpha6beta1 on vascular endothelial growth
      factor (VEGF) expression because autocrine VEGF is necessary for the survival of
      serum-deprived cells in hypoxia. The results obtained indicate that alpha6beta1
      is necessary for VEGF expression because the ability of hypoxia to activate HIF-1
      and to stimulate VEGF transcription in MDA-MB-435 cells is dependent on
      alpha6beta1 expression by a mechanism that involves protein kinase C-alpha.

PMID- 15256437
TI  - Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung
      cancer.
AB  - Aberrant activation of the Wingless-type (Wnt) signaling pathway is associated
      with a variety of human cancers, and we recently reported the importance of
      aberrant Wnt signaling in lung cancer. On the other hand, inhibition of Wnt
      signaling suppresses growth in numerous cell types. Wnt inhibitory factor-1 (WIF
      1) is a secreted antagonist that can bind Wnt in the extracellular space and
      inhibit Wnt signaling. Recently, down-regulation of WIF-1 has been reported in
      several human cancers. To discover the mechanism of WIF-1 silencing in lung
      cancer, we first identified the human WIF-1 promoter and subsequently examined
      the methylation status in the CpG islands. By using methylation-specific PCR and
      sequence analysis after bisulfite treatment, we demonstrate here frequent CpG
      island hypermethylation in the functional WIF-1 promoter region. This
      hypermethylation correlates with its transcriptional silencing in human lung
      cancer cell lines. Moreover, treatment with 5-aza-2'-deoxycytidine restores WIF-1
      expression. We then studied WIF-1 expression in 18 freshly resected lung cancers,
      and we show a down-regulation in 15 of them (83%). This silencing also correlates
      with WIF-1 promoter methylation. Our results suggest that methylation silencing
      of WIF-1 is a common and likely important mechanism of aberrant activation of the
      Wnt signaling pathway in lung cancer pathogenesis, raising its therapeutic
      interest.

PMID- 15256438
TI  - Mismatch repair gene PMS2: disease-causing germline mutations are frequent in
      patients whose tumors stain negative for PMS2 protein, but paralogous genes
      obscure mutation detection and interpretation.
AB  - The MutLalpha heterodimer formed by mismatch repair (MMR) proteins MLH1 and PMS2
      is a major component of the MMR complex, yet mutations in the PMS2 gene are rare
      in the etiology of hereditary nonpolyposis colorectal cancer. Evidence from five
      published cases suggested that contrary to the Knudson principle, PMS2 mutations
      cause hereditary nonpolyposis colorectal cancer or Turcot syndrome only when they
      are biallelic in the germline or abnormally expressed. As candidates for PMS2
      mutations, we selected seven patients whose colon tumors stained negative for
      PMS2 and positive for MLH1 by immunohistochemistry. After conversion to haploidy,
      truncating germline mutations of PMS2 were found in two patients (2192delTAACT
      and deletion of exon 8). These mutations abrogated PMS2 protein in germline cells
      by Western analysis. In two additional patients, PMS2 protein from one allele
      also was abrogated. Novel or previously described missense variants of PMS2 were
      detected, but their pathogenicity is undetermined. We detected and characterized
      a new transcript, PMS2CL, showing 98% sequence identity with exons 9 and 11-15 of
      PMS2 and emanating from a locus close to PMS2 in chromosome 7p. Its predicted
      protein product was not detected. Thus, in addition to several previously
      described PMS2-related genes resembling the 5' end of PMS2, at least one related
      gene resembles the 3' end of PMS2. In conclusion, both detectable and presently
      undefined germline mutations are deleterious and produce susceptibility to cancer
      by the two-hit mechanism. Paralogous genes interfere with mutation detection,
      resulting in underdiagnosis of PMS2 mutations. Mutation detection in PMS2
      requires haploid DNA.

PMID- 15256439
TI  - The expression of Sprouty1, an inhibitor of fibroblast growth factor signal
      transduction, is decreased in human prostate cancer.
AB  - A considerable body of evidence indicates that alterations of fibroblast growth
      factors (FGFs) and their receptors contribute to prostate cancer progression.
      Recently, a new family of regulators of FGF activity has been identified. The
      Sprouty gene family negatively regulates FGF signaling in a variety of systems
      and could potentially limit the biological activity of FGFs in prostate cancer.
      Immunohistochemical analysis of normal and neoplastic prostate tissues using
      tissue microarrays revealed that Sprouty1 protein is down-regulated in
      approximately 40% of prostate cancers when compared with matched normal prostate.
      By quantitative real-time PCR analysis, we found that Sprouty1 mRNA levels were
      significantly decreased in prostate cancers in vivo in comparison with normal
      prostate. In prostate cancer cell lines, there is loss of the normal up
      regulation of Sprouty1 mRNA and protein in response to FGFs. The decrease in
      Sprouty1 expression in the human prostate cancer, despite elevated levels of FGF
      ligands and FGF receptors, implies a loss of an important growth regulatory
      mechanism in prostate cancers that may potentiate the effects of increased FGF
      and FGF receptor expression in prostate cancer.

PMID- 15256440
TI  - Embryonic stem cell-like features of testicular carcinoma in situ revealed by
      genome-wide gene expression profiling.
AB  - Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous
      testicular germ cell tumors (TGCTs), which in recent decades have markedly
      increased and now are the most common malignancy of young men. Using genome-wide
      gene expression profiling, we identified >200 genes highly expressed in
      testicular CIS, including many never reported in testicular neoplasms. Expression
      was further verified by semiquantitative reverse transcription-PCR and in situ
      hybridization. Among the highest expressed genes were NANOG and POU5F1, and
      reverse transcription-PCR revealed possible changes in their stoichiometry on
      progression into embryonic carcinoma. We compared the CIS expression profile with
      patterns reported in embryonic stem cells (ESCs), which revealed a substantial
      overlap that may be as high as 50%. We also demonstrated an over-representation
      of expressed genes in regions of 17q and 12, reported as unstable in cultured
      ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS.
      Moreover, the findings are consistent with an early prenatal origin of TGCTs and
      thus suggest that etiologic factors operating in utero are of primary importance
      for the incidence trends of TGCTs. Finally, some of the highly expressed genes
      identified in this study are promising candidates for new diagnostic markers for
      CIS and/or TGCTs.

PMID- 15256441
TI  - High-resolution global profiling of genomic alterations with long oligonucleotide
      microarray.
AB  - Cancer represents the phenotypic end point of multiple genetic lesions that endow
      cells with a full range of biological properties required for tumorigenesis.
      Among the hallmark features of the cancer genome are recurrent regional gains and
      losses that, upon detailed characterization, have provided highly productive
      discovery paths for new oncogenes and tumor suppressor genes. In this study, we
      describe the use of an oligonucleotide-based microarray platform and development
      of requisite assay conditions and bioinformatic mining tools that permits high
      resolution genome-wide array-comparative genome hybridization profiling of human
      and mouse tumors. Using a commercially available 60-mer oligonucleotide
      microarray, we demonstrate that this platform provides sufficient sensitivity to
      detect single-copy difference in gene dosage of full complexity genomic DNA while
      offering high resolution. The commercial availability of the microarrays and
      associated reagents, along with the technical protocols and analytical tools
      described in this report, should provide investigators with the immediate
      capacity to perform DNA analysis of normal and diseased genomes in a global and
      detailed manner.

PMID- 15256442
TI  - Ser392 phosphorylation regulates the oncogenic function of mutant p53.
AB  - Despite the wealth of information on the regulation of wild-type p53 function by
      phosphorylation, nothing is known about the biological effect of phosphorylation
      on mutant p53. Here we show that p53H175 is phosphorylated like wild-type p53 in
      cells of the same background. Ser(392) nonphosphorylatable p53 mutants
      p53H175A392 and p53W248A392 more potently transformed rat embryo fibroblasts in
      cooperation with the ras oncogene than p53H175S392 and p53W248S392. p53H175A392
      also had an enhanced ability to confer cellular resistance to the cytotoxic
      effect of cisplatin and UV radiation. This correlated with p53H175A392 being a
      more potent dominant negative mutant than p53H175 in inhibiting the apoptotic
      functions of wild-type p53. Moreover, p53H175E392, which mimics the
      phosphorylated form of p53H175, was less able to confer cellular resistance to
      DNA-damaging agents. p53H175 and p53W248 are phosphorylated like wild-type p53 in
      cells of the same background. Ser(392) nonphosphorylated p53 was present in human
      breast tumors expressing mutant p53 including p53H175. Together, these results
      demonstrated a novel function of Ser(392) phosphorylation in regulating the
      oncogenic function of mutant p53.

PMID- 15256443
TI  - Progression from normal breast pathology to breast cancer is associated with
      increasing prevalence of mouse mammary tumor virus-like sequences in men and
      women.
AB  - Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of
      breast cancer samples but in <2% of normal breast tissue samples from Australian
      women studied by our group. Screening of a larger and more diverse cohort of
      female breast cancer samples has now shown a correlation of MMTV-like sequences
      with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of
      female breast cancer samples were positive for MMTV-like sequences when screened
      using PCR. A significant gradient of MMTV positivity was observed with increasing
      severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors
      to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P =
      0.00002). We also report for the first time the detection of MMTV-like sequences
      in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male
      gynecomastia samples screened. MMTV-like sequences were demonstrated in various
      premalignant breast lesions of females, including fibroadenoma (20%) and
      fibrocystic disease (28%) samples, at a significantly higher prevalence than that
      seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort
      of female breast cancer patients indicated that MMTV was co-incident with tumor
      but was not present when tumor was absent on histology. These results support the
      association of MMTV-like sequences with development of breast tumors in men and
      women and suggest association of MMTV with increasing severity of cancer.

PMID- 15256444
TI  - Hypersensitivity of tumor cell lines with microsatellite instability to DNA
      double strand break producing chemotherapeutic agent bleomycin.
AB  - Genetic or epigenetic inactivation of DNA mismatch repair genes results in a
      strong mutator phenotype, known as the microsatellite mutator phenotype or
      microsatellite instability (MSI). This mutator phenotype causes mutations in
      genes responsible for the regulation of cell growth and survival/death and thus
      promotes the development and progression of tumors. In addition to such
      tumorigenic lesions, mutations in genes of other types of DNA repair, for
      example, DNA double-strand break (DNA DSB) repair, are found in tumor cells with
      MSI. We report here that the majority of MSI-positive tumor cell lines of
      different tissue origins (endometrial, ovarian, prostate, and colorectal
      carcinomas) are hypersensitive to bleomycin, a DNA DSB producing chemotherapeutic
      drug. We suggest that this hypersensitivity may be a result of inactivation of
      the DNA DSB repair activity by concomitant mutations of different DNA DSB repair
      genes. To provide experimental support to this hypothesis, we show that the
      subclones of the MSI-positive colorectal cancer cell line HCT-8 that bear
      heterozygous frameshift mutations in the DNA DSB repair gene DNA-PK(CS) are more
      sensitive to a combined treatment with bleomycin and the DNA protein kinase
      inhibitor LY294002 than the original HCT-8 cells, which are wild type for this
      gene. These results may be useful in designing therapies for MSI-positive cancer.

PMID- 15256445
TI  - Collagenase increases the transcapillary pressure gradient and improves the
      uptake and distribution of monoclonal antibodies in human osteosarcoma
      xenografts.
AB  - Cancer therapy based on tumor-selective macromolecules may fail due to the
      elevated interstitial fluid pressure (IFP) that reduces the transvascular and
      interstitial convection in solid tumors. Modulation of the tumor extracellular
      matrix (ECM) may reduce IFP and enhance transvascular filtration and interstitial
      transport of macromolecules. We therefore measured the effect of the ECM
      degrading enzyme collagenase on IFP and microvascular pressure (MVP) in human
      osteosarcoma xenografts using the wick-in-needle and micropipette methods,
      respectively. The tumor uptake and distribution of a systemically administered
      osteosarcoma-associated monoclonal antibody (TP-3) after i.v. injection of
      collagenase were analyzed using confocal laser scanning microscopy. Collagenase
      (0.1%) reduced both IFP (45%) and MVP (60%), but the kinetics of the recoveries
      differed, because MVP had recovered by the time IFP reached its minimum level.
      Thus, collagenase increased the transcapillary pressure gradient, inducing a 2
      fold increase in the tumor uptake and improving the distribution of the
      monoclonal antibody, which was localized further into the tumor. To study the
      mechanism of the reduction in MVP, mean arterial blood pressure was measured and
      found not to be affected by the collagenase treatment. The reduction in MVP was
      rather due to reduced vascular resistance because microvascular-associated
      collagen was totally or partially disintegrated. Although collagenase may favor
      metastasis and thus not be clinically relevant, this study shows proof of
      principle that degradation of the ECM leads to a favorable change in the
      transvascular pressure gradient, thereby increasing antibody penetration and
      binding to tumor cells.

PMID- 15256446
TI  - Activation of signal transducer and activator of transcription 5 in human
      prostate cancer is associated with high histological grade.
AB  - We have recently identified signal transducer and activator of transcription 5
      (Stat5) as a critical survival factor for prostate cancer cells. We now report
      that activation of Stat5 is associated with high histological grade of human
      prostate cancer. Specifically, immunohistochemical analysis demonstrated a strong
      positive correlation with activation of Stat5 and high Gleason score in 114 human
      prostate cancers. To investigate the mechanisms underlying constitutive
      activation of Stat5 in prostate cancer, a dominant-negative mutant of Janus
      kinase 2 (Jak2) was delivered by adenovirus to CWR22Rv cells. Dominant-negative
      Jak2 effectively blocked the activation of Stat5 whereas wild-type Jak2 enhanced
      activation, indicating that Jak2 is the main kinase that phosphorylates Stat5 in
      human prostate cancer cells. A ligand-induced mechanism for activation of Stat5
      in prostate cancer was suggested by the ability of prolactin (Prl) to stimulate
      activation of both Jak2 and Stat5 in CWR22Rv human prostate cancer cells and in
      CWR22Rv xenograft tumors. In addition, Prl restored constitutive activation of
      Stat5 in five of six human prostate cancer specimens in ex vivo long-term organ
      cultures. Finally, Prl protein was locally expressed in the epithelium of 54% of
      80 human prostate cancer specimens with positive correlation with high Gleason
      scores and activation of Stat5. In conclusion, our data indicate that increased
      activation of Stat5 was associated with more biologically aggressive behavior of
      prostate cancer. The results further suggest that Jak2 is the principal Stat5
      tyrosine kinase in human prostate cancer, possibly activated by
      autocrine/paracrine Prl.

PMID- 15256447
TI  - Dose-dependent effects of platelet-derived growth factor-B on glial
      tumorigenesis.
AB  - Platelet-derived growth factor (PDGF) is expressed in many different tumors, but
      its precise roles in tumorigenesis remain to be fully defined. Here, we report on
      a mouse model that demonstrates dose-dependent effects of PDGF-B on glial
      tumorigenesis. By removing inhibitory regulatory elements in the PDGFB mRNA, we
      are able to substantially elevate its expression in tumor cells using a
      retroviral delivery system. This elevation in PDGF-B production results in tumors
      with shortened latency, increased cellularity, regions of necrosis, and general
      high-grade character. In addition, elevated PDGF-B in these tumors also mediates
      vascular smooth muscle cell recruitment that supports tumor angiogenesis. PDGF
      receptor (PDGFR) signaling appears to be required for the maintenance of these
      high-grade characteristics, because treatment of high-grade tumors with a small
      molecule inhibitor of PDGFR results in reversion to a lower grade tumor
      histology. Our data show that PDGFR signaling quantitatively regulates tumor
      grade and is required to sustain high-grade oligodendrogliomas.

PMID- 15256448
TI  - The tumor microenvironment controls primary effusion lymphoma growth in vivo.
AB  - Certain lymphomas in AIDS patients, such as primary effusion lymphoma (PEL), are
      closely associated with the lymphotropic gamma herpes virus Kaposi's sarcoma
      associated herpes virus (KSHV), also called human herpesvirus 8. The virus is
      thought to be essential for tumorigenesis, yet systems to investigate PEL in vivo
      are rare. Here we describe PEL tumorigenesis in a new xenograft model. Embedded
      in Matrigel, PEL cells formed rapid, well-organized, and angiogenic tumors after
      s.c. implantation of C.B.17 SCID mice. Without Matrigel we did not observe
      comparable tumors, which implies that extracellular support and/or signaling aids
      PEL. All of the tumors maintained the KSHV genome, and the KSHV latent protein
      LANA/orf73 was uniformly expressed. However, the expression profile for key lytic
      mRNAs, as well as LANA-2/vIRF3, differed between tissue culture and sites of
      implantation. We did not observe a net effect of ganciclovir on PEL growth in
      culture or as xenograft. These findings underscore the importance of the
      microenvironment for PEL tumorigenesis and simplify the preclinical evaluation of
      potential anticancer agents.

PMID- 15256449
TI  - Induction of centrosome amplification and chromosome instability in human bladder
      cancer cells by p53 mutation and cyclin E overexpression.
AB  - Centrosome amplification frequently occurs in human cancers and is a major cause
      of chromosome instability (CIN). In mouse cells, centrosome amplification can be
      readily induced by loss or mutational inactivation of p53. In human cells,
      however, silencing of endogenous p53 alone does not induce centrosome
      amplification or CIN, although high degrees of correlation between p53 mutation
      and CIN/centrosome amplification in human cancer can be detected, suggesting the
      presence of additional regulatory mechanism(s) in human cells that ensures the
      numeral integrity of centrosomes and genomic integrity. Cyclin E, a regulatory
      subunit for CDK2 that plays a key role in centrosome duplication, frequently is
      overexpressed in human cancers. We found that cyclin E overexpression, together
      with loss of p53, efficiently induces centrosome amplification and CIN in human
      bladder cancer cells but not by either cyclin E overexpression or loss of p53
      alone. We extended these findings to bladder cancer specimens and found that
      centrosome amplification is strongly correlated with concomitant occurrence of
      cyclin E overexpression and p53 inactivation but not with either cyclin E
      overexpression or p53 inactivation alone. Because cyclin E expression is strictly
      controlled in human cells compared with mouse cells, our findings suggest that
      this stringent regulation of cyclin E expression plays an additional role
      underlying numeral homeostasis of centrosomes in human cells and that
      deregulation of cyclin E expression, together with inactivation of p53, results
      in centrosome amplification.

PMID- 15256450
TI  - Identification of an active site on the laminin alpha5 chain globular domain that
      binds to CD44 and inhibits malignancy.
AB  - The laminin alpha5 chain is a component of laminin-10 (alpha5beta1gamma1) and -11
      (alpha5beta2gamma1). In this study, we have screened 113 overlapping synthetic
      peptides from the laminin alpha5 globular domain (G-domain) for cell attachment
      activity with B16-F10 cells using peptide-coated dishes. Eleven attachment-active
      peptides were identified. In vivo experimental B16-F10 pulmonary metastasis and
      primary tumor growth assays found that 4 of the 11 peptides inhibited tumor
      metastasis and growth and increased apoptosis. These four peptides also blocked
      tumor cell migration, invasion, and angiogenesis. Two of the peptides were highly
      homologous and showed significant similarity to sequences in collagens. We sought
      to identify the B16-F10 cell surface receptors for each of the four active
      peptides using peptide affinity chromatography. Only one peptide recognized a
      cell surface protein. Peptide A5G27 (RLVSYNGIIFFLK, residues 2892-2904) bound a
      diffuse M(r) approximately 120,000-180,000 band that eluted with 2 m NaCl.
      Glycosidase digestion of the 2 m eluate yielded protein bands of M(r) 90,000 and
      60,000 that reacted in Western blot analysis with antibodies to CD44.
      Immunoprecipitation of the A5G27-bound membrane proteins with various cell
      surface proteoglycan antibodies confirmed CD44 as the surface receptor for A5G27.
      Finally, attachment assays to A5G27 in the presence of soluble glycosaminoglycans
      (GAGs) identified the GAGs of CD44 as the binding sites for A5G27. Our results
      suggest that A5G27 binds to the CD44 receptor of B16-F10 melanoma cells via the
      GAGs on CD44 and, thus, inhibits tumor cell migration, invasion, and angiogenesis
      in a dominant-negative manner.

PMID- 15256451
TI  - Array comparative genomic hybridization analysis of colorectal cancer cell lines
      and primary carcinomas.
AB  - Array comparative genomic hybridization, with a genome-wide resolution of
      approximately 1 Mb, has been used to investigate copy number changes in 48
      colorectal cancer (CRC) cell lines and 37 primary CRCs. The samples were divided
      for analysis according to the type of genomic instability that they exhibit,
      microsatellite instability (MSI) or chromosomal instability (CIN). Consistent
      copy number changes were identified, including gain of chromosomes 20, 13, and 8q
      and smaller regions of amplification such as chromosome 17q11.2-q12. Loss of
      chromosome 18q was a recurrent finding along with deletion of discrete regions
      such as chromosome 4q34-q35. The overall pattern of copy number change was
      strikingly similar between cell lines and primary cancers with a few obvious
      exceptions such as loss of chromosome 6 and gain of chromosomes 15 and 12p in the
      former. A greater number of aberrations were detected in CIN+ than MSI+ samples
      as well as differences in the type and extent of change reported. For example,
      loss of chromosome 8p was a common event in CIN+ cell lines and cancers but was
      often found to be gained in MSI+ cancers. In addition, the target of
      amplification on chromosome 8q appeared to differ, with 8q24.21 amplified
      frequently in CIN+ samples but 8q24.3 amplification a common finding in MSI+
      samples. A number of genes of interest are located within the frequently
      aberrated regions, which are likely to be of importance in the development and
      progression of CRC.

PMID- 15256452
TI  - Identification of decatenation G2 checkpoint impairment independently of DNA
      damage G2 checkpoint in human lung cancer cell lines.
AB  - It has been suggested that attenuation of the decatenation G(2) checkpoint
      function, which ensures sufficient chromatid decatenation by topoisomerase II
      before entering into mitosis, may contribute to the acquisition of genetic
      instability in cancer cells. To date, however, very little information is
      available on this type of checkpoint defect in human cancers. In this study, we
      report for the first time that a proportion of human lung cancer cell lines did
      not properly arrest before entering mitosis in the presence of a catalytic,
      circular cramp-forming topoisomerase II inhibitor ICRF-193, whereas the
      decatenation G(2) checkpoint impairment was present independently of the impaired
      DNA damage G(2) checkpoint. In addition, the presence of decatenation G(2)
      checkpoint dysfunction was found to be associated with diminished activation of
      ataxia-telangiectasia mutated in response to ICRF-193, suggesting the potential
      involvement of an upstream pathway sensing incompletely catenated chromatids.
      Interestingly, hypersensitivity to ICRF-193 was observed in cell lines with
      decatenation G(2) checkpoint impairment and negligible activation of ataxia
      telangiectasia mutated. These findings suggest the possible involvement of
      decatenation G(2) checkpoint impairment in the development of human lung cancers,
      as well as the potential clinical implication of selective killing of lung cancer
      cells with such defects by this type of topoisomerase II inhibitor.

PMID- 15256453
TI  - Rapid inhibition of cancer cell growth induced by lentiviral delivery and
      expression of mutant-template telomerase RNA and anti-telomerase short
      interfering RNA.
AB  - In human cancers, telomeres are commonly maintained by elevated levels of the
      ribonucleoprotein enzyme telomerase, which contains an intrinsic templating RNA
      moiety (human telomerase RNA; hTER) and the core protein (human telomerase
      reverse transcriptase). We developed a lentiviral system for efficient
      overexpression of mutant-template human telomerase RNA (MT-hTer) to add mutant
      DNA to telomeres in cancer cells. We show that such MT-hTer overexpression
      rapidly inhibits cell growth and induces apoptosis in telomerase-positive
      precancerous or cancer cells but not in telomerase-negative cells. These rapid
      effects occurred independent of wild-type p53 and telomere length. Tumor growth
      and progression were significantly decreased in xenografts of human tumor cells
      overexpressing MT-hTers. Expression of a hairpin short-interfering RNA that
      specifically targeted the endogenous wild-type hTER template region, but spared
      the MT-hTers, also caused p53-independent cell growth inhibition and apoptosis,
      and when coexpressed with MT-hTer, synergistically killed cancer cells. Hence,
      anti-wild-type-hTER short-interfering RNA and MT-hTers may act through distinct
      pathways and, particularly in combination, represent a promising approach to
      anticancer therapies.

PMID- 15256454
TI  - Bcl-2-dependent modulation of swelling-activated Cl- current and ClC-3 expression
      in human prostate cancer epithelial cells.
AB  - Cell shrinkage is an integral part of apoptosis. However, intimate mechanisms
      linking apoptotic events to the alterations in cell volume homeostasis remain
      poorly elucidated. We investigated how overexpression of Bcl-2 oncoprotein, a key
      antiapoptotic regulator, in lymph node carcinoma of the prostate (LNCaP) prostate
      cancer epithelial cells interferes with the volume-regulated anion channel
      (VRAC), a major determinant of regulatory volume decrease. Bcl-2 overexpression
      resulted in the doubling of VRAC-carried swelling-activated Cl(-) current
      (I(Cl,swell)) and weakened I(Cl,swell) inhibition by store-operated Ca(2+)
      channel (SOC)-transported Ca(2+). This also was accompanied by substantial up
      regulation of ClC-3 protein, a putative molecular candidate for the role of VRAC.
      ClC-3-specific antibody suppressed I(Cl,swell) in the wild-type and Bcl-2
      overexpressing LNCaP cells. Epidermal growth factor treatment of wild-type LNCaP
      cells, promoting their proliferation, resulted in the enhancement of endogenous
      Bcl-2 expression and associated increases in ClC-3 levels and I(Cl,swell)
      magnitude. We conclude that Bcl-2-induced up-regulation of I(Cl,swell), caused by
      enhanced expression of ClC-3 and weaker negative control from SOC-transported
      Ca(2+), would strengthen the ability of the cells to handle proliferative volume
      increases and thereby promote their survival and diminish their proapoptotic
      potential.

PMID- 15256455
TI  - Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum
      based anticancer agents.
AB  - Tumors frequently contain mutations in the ras genes, resulting in the
      constitutive activation of the Ras-activated signaling pathway. The activation of
      Ras is involved not only in tumor progression but also in the development of
      resistance of the tumor cells to platinum-based chemotherapeutic agents. To
      investigate the potential mechanisms underlying this resistance, we analyzed the
      effect of activated H-Ras on the expression of the nucleotide excision repair
      genes. Here we identified ERCC1, which is one of the key enzymes involved in
      nucleotide excision repair, as being markedly up-regulated by the activated H
      Ras. From promoter analysis of ERCC1, an increase in the Ap1 transcriptional
      activity as a result of the expression of the oncogenic H-Ras was found to be
      crucial for this induction. In addition, ERCC1 small interfering RNA expression
      was shown to reduce the oncogenic H-Ras-mediated increase in the DNA repair
      activity as well as to suppress the oncogenic H-Ras-mediated resistance of the
      cells to platinum-containing chemotherapeutic agents. These results suggest that
      the oncogenic H-Ras-induced ERCC1, which activates the DNA repair capacity, may
      be involved in the protection of the cells against platinum-based anticancer
      agents.

PMID- 15256456
TI  - Expression of angiogenic factors vascular endothelial growth factor and
      interleukin-8/CXCL8 is highly responsive to ambient glutamine availability: role
      of nuclear factor-kappaB and activating protein-1.
AB  - Vascular endothelial growth factor (VEGF) and interleukin-8/CXCL8 (IL-8) are
      prominent pro-angiogenic and pro-metastatic proteins that represent negative
      prognostic factors in many types of cancer. Hypoxia is thought to be the primary
      environmental cause of VEGF and IL-8 expression in solid tumors. We hypothesized
      that a lack of nutrients other than oxygen could stimulate the expression of
      these factors and previously demonstrated that expression of VEGF and IL-8 is
      responsive to amino acid deprivation. In the present study, we examined the
      effect of glutamine availability on the expression of these factors as well as
      the role of transcription factors NFkappaB and activating protein-1 (AP-1) in the
      response of TSE human breast carcinoma cells to glutamine deprivation. VEGF and
      IL-8 secretion and mRNA levels were dramatically induced by glutamine
      deprivation. mRNA stabilization contributed to this response. Glutamine
      deprivation increased NFkappaB (p65/p50) and AP-1 (Fra-1/c-Jun+JunD) DNA-binding
      activities. Blocking NFkappaB and AP-1 activation with curcumin as well as
      expression of dominant inhibitors, inhibitor of nuclear factor-kappaB (IkappaB)
      super repressor (IkappaBM), and a mutant form of c-Fos (A-Fos) demonstrated that
      the activation of NFkappaB and AP-1 transcription factors was necessary for the
      induction of IL-8 expression but dispensable for the induction of VEGF
      expression. A macro-array containing 111 NFkappaB target genes identified a total
      of 17 that were up-regulated 2-fold or more in response to glutamine deprivation.
      These included growth regulated oncogene alpha (GROalpha/GRO1/CXCL1), another
      neutrophil chemoattractant implicated in tumor angiogenesis and metastasis.

PMID- 15256457
TI  - A fully human antitumor immunoRNase selective for ErbB-2-positive carcinomas.
AB  - We report the preparation and characterization of a novel, fully human antitumor
      immunoRNase (IR). The IR, a human RNase and fusion protein made up of a human
      single chain variable fragment (scFv), is directed to the ErbB-2 receptor and
      overexpressed in many carcinomas. The anti-ErbB-2 IR, named hERB-hRNase, retains
      the enzymatic activity of the wild-type enzyme (human pancreatic RNase) and
      specifically binds to ErbB-2-positive cells with the high affinity (K(d) = 4.5
      nm) of the parental scFv. hERB-hRNase behaves as an immunoprotoxin and on
      internalization by target cells becomes selectively cytotoxic in a dose-dependent
      manner at nanomolar concentrations. Administered in five doses of 1.5 mg/kg to
      mice bearing an ErbB-2-positive tumor, hERB-hRNase induced a dramatic reduction
      in tumor volume. hERB-hRNase is the first fully human antitumor IR produced thus
      far, with a high potential as a poorly immunogenic human drug devoid of
      nonspecific toxicity, directed against ErbB-2-positive malignancies.

PMID- 15256458
TI  - Small molecule antagonists of the sigma-1 receptor cause selective release of the
      death program in tumor and self-reliant cells and inhibit tumor growth in vitro
      and in vivo.
AB  - The acquisition of resistance to apoptosis, the cell's intrinsic suicide program,
      is essential for cancers to arise and progress and is a major reason behind
      treatment failures. We show in this article that small molecule antagonists of
      the sigma-1 receptor inhibit tumor cell survival to reveal caspase-dependent
      apoptosis. sigma antagonist-mediated caspase activation and cell death are
      substantially attenuated by the prototypic sigma-1 agonists (+)-SKF10,047 and (+)
      pentazocine. Although several normal cell types such as fibroblasts, epithelial
      cells, and even sigma receptor-rich neurons are resistant to the apoptotic
      effects of sigma antagonists, cells that can promote autocrine survival such as
      lens epithelial and microvascular endothelial cells are as susceptible as tumor
      cells. Cellular susceptibility appears to correlate with differences in sigma
      receptor coupling rather than levels of expression. In susceptible cells only,
      sigma antagonists evoke a rapid rise in cytosolic calcium that is inhibited by
      sigma-1 agonists. In at least some tumor cells, sigma antagonists cause calcium
      dependent activation of phospholipase C and concomitant calcium-independent
      inhibition of phosphatidylinositol 3'-kinase pathway signaling. Systemic
      administration of sigma antagonists significantly inhibits the growth of evolving
      and established hormone-sensitive and hormone-insensitive mammary carcinoma
      xenografts, orthotopic prostate tumors, and p53-null lung carcinoma xenografts in
      immunocompromised mice in the absence of side effects. Release of a sigma
      receptor-mediated brake on apoptosis may offer a new approach to cancer
      treatment.

PMID- 15256459
TI  - Efflux kinetics and intracellular distribution of daunorubicin are not affected
      by major vault protein/lung resistance-related protein (vault) expression.
AB  - Vaults may contribute to multidrug resistance by transporting drugs away from
      their subcellular targets. To study the involvement of vaults in the extrusion of
      anthracyclines from the nucleus, we investigated the handling of daunorubicin by
      drug-sensitive and drug-resistant non-small lung cancer cells, including a green
      fluorescent protein (GFP)-tagged major vault protein (MVP)-overexpressing
      transfectant (SW1573/MVP-GFP). Cells were exposed to 1 microm daunorubicin for 60
      min, after which the cells were allowed to efflux the accumulated drug. No
      significant differences in daunorubicin efflux kinetics were observed between the
      sensitive SW1573 and SW1573/MVP-GFP transfectant, whereas the drug-resistant
      SW1573/2R120 cells clearly demonstrated an increased efflux rate. It was noted
      that the redistribution of daunorubicin from the nucleus into distinct vesicular
      structures in the cytoplasm was not accompanied by changes in the intracellular
      localization of vaults. Similar experiments were performed using mouse embryonic
      fibroblasts derived from wild-type and MVP knockout mice, which were previously
      shown to be devoid of vault particles. Both cell lines showed comparable drug
      efflux rates, and the intracellular distribution of daunorubicin in time was
      identical. Reintroduction of a human MVP tagged with GFP in the MVP(-/-) cells
      results in the formation of vault particles but did not give rise an altered
      daunorubicin handling compared with MVP(-/-) cells expressing GFP. Our results
      indicate that vaults are not directly involved in the sequestration of
      anthracyclines in vesicles nor in their efflux from the nucleus.

PMID- 15256460
TI  - A specific antagonist of the p110delta catalytic component of
      phosphatidylinositol 3'-kinase, IC486068, enhances radiation-induced tumor
      vascular destruction.
AB  - The phosphatidylinositol 3'-kinase (PI3k)/protein kinase B (PKB/Akt) signal
      transduction pathway plays a critical role in mediating endothelial cell survival
      and function during oxidative stress. The role of the PI3k/Akt signaling pathway
      in promoting cell viability was studied in vascular endothelial cells treated
      with ionizing radiation. Western blot analysis showed that Akt was rapidly
      phosphorylated in response to radiation in primary culture endothelial cells
      (human umbilical vascular endothelial cells) in the absence of serum or growth
      factors. PI3k consists of p85 and p110 subunits, which play a central upstream
      role in Akt activation in response to exogenous stimuli. The delta isoform of the
      p110 subunit is expressed in endothelial cells. We studied the effects of the
      p110delta specific inhibitor IC486068, which abrogated radiation-induced
      phosphorylation of Akt. IC486068 enhanced radiation-induced apoptosis in
      endothelial cells and reduced cell migration and tubule formation of endothelial
      cells in Matrigel following irradiation. In vivo tumor growth delay was studied
      in mice with Lewis lung carcinoma and GL261 hind limb tumors. Mice were treated
      with daily i.p. injections (25 mg/kg) of IC486068 during 6 days of radiation
      treatment (18 Gy). Combined treatment with IC486068 and radiation significantly
      reduced tumor volume as compared with either treatment alone. Reduction in
      vasculature was confirmed using the dorsal skinfold vascular window model. The
      vascular length density was measured by use of the tumor vascular window model
      and showed IC486068 significantly enhanced radiation-induced destruction of tumor
      vasculature as compared with either treatment alone. IC486068 enhances radiation
      induced endothelial cytotoxicity, resulting in tumor vascular destruction and
      tumor control when combined with fractionated radiotherapy in murine tumor
      models. These findings suggest that p110delta is a therapeutic target to enhance
      radiation-induced tumor control.

PMID- 15256461
TI  - Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates
      with chemotherapy to inhibit orthotopic lung tumor growth and improve survival.
AB  - Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL)
      is a tumor necrosis factor superfamily member that induces apoptosis through the
      death receptors DR4 and/or DR5 in various cancer cell types but not in most
      normal cells. Several lung cancer cell lines express DR4 and DR5 and undergo
      apoptosis in vitro in response to Apo2L/TRAIL. We investigated the efficacy of
      recombinant soluble human Apo2L/TRAIL and its interaction with chemotherapy in
      xenograft models based on human NCI-H460 non-small cell lung carcinoma cells. In
      vitro, Taxol enhanced caspase activation and apoptosis induction by Apo2L/TRAIL.
      In vivo, Apo2L/TRAIL or Taxol plus carboplatin chemotherapy partially delayed
      progression of established subcutaneous tumor xenografts, whereas combined
      treatment caused tumor regression and a substantially longer growth delay.
      Apo2L/TRAIL, chemotherapy, or the combination of both inhibited growth of
      preformed orthotopic lung parenchymal tumors versus control by 60%, 57%, or 97%,
      respectively (all P < 0.01; n = 8-10). Furthermore, combination treatment
      improved day-90 survival relative to control (7 of 15 versus 1 of 15; P = 0.0003
      by Mantel-Cox) as well as to Apo2L/TRAIL (3 of 14; P = 0.031) or chemotherapy (3
      of 15; P = 0.035). These studies provide evidence for in vivo activity of
      Apo2L/TRAIL against lung tumor xenografts and underscore the potential of this
      ligand for advancing current lung cancer treatment strategies.

PMID- 15256462
TI  - Noninvasive imaging of the transcriptional activities of human telomerase
      promoter fragments in mice.
AB  - We have assessed the feasibility of positron emission tomography (PET) and ex
      vivo gamma-counting to measure the pattern of expression of telomerase promoter
      fragments in vivo. Promoter fragments from either the RNA [human telomerase RNA
      (hTR)] or the catalytic components [human telomerase reverse transcriptase
      (hTERT)] of the telomerase genes were used to drive the expression of the sodium
      iodide symporter PET reporter gene in recombinant adenoviruses. Both promoter
      fragments provided cancer-selective expression that could be visualized and
      quantitated by PET. The transcriptional activity of the hTR promoter was found to
      be consistently stronger than that of the hTERT promoter. Both promoters appear
      therefore to be good candidates for safe use in gene therapy, and PET imaging can
      be used to assess the selectivity of promoters in vivo. Given that this
      methodology is directly scalable to humans, imaging gene expression using the
      sodium iodide symporter PET reporter gene could be applied to measure telomerase
      promoter activity in humans.

PMID- 15256463
TI  - Augmenting chemosensitivity of malignant melanoma tumors via proteasome
      inhibition: implication for bortezomib (VELCADE, PS-341) as a therapeutic agent
      for malignant melanoma.
AB  - Melanoma poses a great challenge to patients, oncologists, and biologists because
      of its nearly universal resistance to chemotherapy. Many studies have shown that
      nuclear factor kappaB is constitutively activated in melanoma, thereby promoting
      the proliferation of melanoma cells by inhibiting the apoptotic responses to
      chemotherapy. Nuclear factor kappaB activity is regulated by phosphorylation and
      subsequent degradation of inhibitor of nuclear factor kappaB by the ubiquitin
      proteasome pathway. In this study, we show that the novel proteasome inhibitor,
      bortezomib, inhibited the growth of melanoma cells in vitro at a concentration
      range of 0.1-10 nM and in combination with the chemotherapeutic agent
      temozolomide, the inhibitory effect on melanoma cell growth was even more
      prominent. Data from a murine model showed reduced tumor growth when bortezomib
      was administered to human melanoma tumors. Strikingly, animals receiving
      bortezomib in combination with temozolomide achieved complete remission of
      palpable tumors after only 30 days of therapy, lasting >200 days. Our data
      indicate strongly that bortezomib in combination with chemotherapeutic agents
      should be studied additionally for the treatment of melanoma.

PMID- 15256464
TI  - High CD46 receptor density determines preferential killing of tumor cells by
      oncolytic measles virus.
AB  - Live attenuated Edmonston B strain of measles virus (MV-Edm) is a potent and
      specific oncolytic agent, but the mechanism underlying its tumor selectivity is
      unknown. The virus causes cytopathic effects (CPEs) of extensive syncytial
      formation in tumor cells but minimal damage or cell killing in normal cells. The
      CPE is dependent on expression of viral proteins and the presence of CD46, the
      major cellular receptor of MV-Edm. Using a virally encoded soluble marker peptide
      to provide a quantitative readout of the level of viral gene expression, we
      determined that tumor cells and normal cells expressed comparable levels of viral
      proteins. CD46 mediates virus attachment, entry, and virus-induced cell-to-cell
      fusion. Using engineered cells expressing a range of CD46 densities, we
      determined that whereas virus entry increased progressively with CD46 density,
      cell fusion was minimal at low receptor densities but increased dramatically
      above a threshold density of CD46 receptors. It is well established that tumor
      cells express abundant CD46 receptors on their surfaces compared with their
      normal counterparts. Thus, at low CD46 densities typical of normal cells,
      infection occurs, but intercellular fusion is negligible. At higher densities
      typical of tumor cells, infection leads to extensive cell fusion. Intercellular
      fusion also results in enhancement of viral gene expression through recruitment
      of neighboring uninfected cells into the syncytium, further amplifying the CPE.
      Discrimination between high and low CD46 receptor density provides a compelling
      basis for the oncolytic specificity of MV-Edm and establishes MV-Edm as a
      promising CD46-targeted cancer therapeutic agent.

PMID- 15256465
TI  - Analysis of the drug resistance profile of multidrug resistance protein 7
      (ABCC10): resistance to docetaxel.
AB  - The multidrug resistance protein (MRP) family consists of nine members that can
      be categorized according to whether or not a third (NH(2)-terminal) membrane
      spanning domain is present. Three (MRP1, MRP2, and MRP3) of the four members that
      have this structural feature are able to confer resistance to natural product
      anticancer agents. We previously established that MRP7, the remaining family
      member that has three membrane-spanning domains, possesses the cardinal
      biochemical activity of MRPs in that it is able to transport amphipathic anions
      such as 17beta-estradiol 17-(beta-d-glucuronide). However, the drug resistance
      profile of the pump has not been determined. In this study, the drug resistance
      capabilities of MRP7 are evaluated by analyzing the resistance profiles of two
      clones of HEK293 cells in which the pump was ectopically expressed. MRP7
      transfected HEK293 cells exhibited the highest levels of resistance toward
      docetaxel (9-13-fold). In addition, lower levels of resistance were observed for
      paclitaxel (3-fold), vincristine (3-fold), and vinblastine (3-4-fold). Consistent
      with the operation of an ATP-dependent efflux pump, MRP7-transfected cells
      exhibited reduced accumulation of radiolabeled paclitaxel compared with HEK293
      cells transfected with parental plasmid. These results indicate that MRP7, unlike
      other MRPs, is a resistance factor for taxanes.

PMID- 15256466
TI  - AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular
      endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and
      antiangiogenic activity.
AB  - Aberrant epidermal growth factor receptor (EGFR) and ErbB2 expression are
      associated with advanced disease and poor patient prognosis in many tumor types
      (breast, lung, ovarian, prostate, glioma, gastric, and squamous carcinoma of head
      and neck). In addition, a constitutively active EGFR type III deletion mutant has
      been identified in non-small cell lung cancer, glioblastomas, and breast tumors.
      Hence, members of the EGFR family are viewed as promising therapeutic targets in
      the fight against cancer. In a similar vein, vascular endothelial growth factor
      (VEGF) receptor kinases are also promising targets in terms of an antiangiogenic
      treatment strategy. AEE788, obtained by optimization of the 7H-pyrrolo[2,3
      d]pyrimidine lead scaffold, is a potent combined inhibitor of both epidermal
      growth factor (EGF) and VEGF receptor tyrosine kinase family members on the
      isolated enzyme level and in cellular systems. At the enzyme level, AEE788
      inhibited EGFR and VEGF receptor tyrosine kinases in the nm range (IC(50)s: EGFR
      2 nm, ErbB2 6 nm, KDR 77 nm, and Flt-1 59 nm). In cells, growth factor-induced
      EGFR and ErbB2 phosphorylation was also efficiently inhibited (IC(50)s: 11 and
      220 nm, respectively). AEE788 demonstrated antiproliferative activity against a
      range of EGFR and ErbB2-overexpressing cell lines (including EGFRvIII-dependent
      lines) and inhibited the proliferation of epidermal growth factor- and VEGF
      stimulated human umbilical vein endothelial cells. These properties, combined
      with a favorable pharmacokinetic profile, were associated with a potent antitumor
      activity in a number of animal models of cancer, including tumors that
      overexpress EGFR and or ErbB2. Oral administration of AEE788 to tumor-bearing
      mice resulted in high and persistent compound levels in tumor tissue. Moreover,
      AEE788 efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation
      in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of
      intermittent treatment schedules. Strikingly, AEE788 also inhibited VEGF-induced
      angiogenesis in a murine implant model. Antiangiogenic activity was also apparent
      by measurement of tumor vascular permeability and interstitial leakage space
      using dynamic contrast enhanced magnetic resonance imaging methodology. Taken
      together, these data indicate that AEE788 has potential as an anticancer agent
      targeting deregulated tumor cell proliferation as well as angiogenic parameters.
      Consequently, AEE788 is currently in Phase I clinical trials in oncology.

PMID- 15256467
TI  - BN80927: a novel homocamptothecin that inhibits proliferation of human tumor
      cells in vitro and in vivo.
AB  - BN80927 belongs to a novel family of camptothecin analogs, the homocamptothecins,
      developed on the concept of topoisomerase I (Topo I) inhibition and characterized
      by a stable seven-membered beta-hydroxylactone ring. Preclinical data reported
      here show that BN80927 retains Topo I poisoning activity in cell-free assay (DNA
      relaxation) as well as in living cells, in which in vivo complexes of
      topoisomerase experiments and quantification of DNA-protein-complexes
      stabilization, have confirmed the higher potency of BN80927 as compared with the
      Topo I inhibitor SN38. In addition, BN80927 inhibits Topo II-mediated DNA
      relaxation in vitro but without cleavable-complex stabilization, thus indicating
      catalytic inhibition. Moreover, a Topo I-altered cell line (KBSTP2), resistant to
      SN38, remains sensitive to BN80927, suggesting that a part of the
      antiproliferative effects of BN80927 are mediated by a Topo I-independent
      pathway. This hypothesis is also supported by in vitro data showing an
      antiproliferative activity of BN80927 on a model of resistance related to the
      noncycling state of cells (G(0)-G(1) synchronized). In cell growth assays,
      BN80927 is a very potent antiproliferative agent as shown by IC(50) values
      consistently lower than those of SN38 in tumor cell lines as well as in their
      related drug-resistant lines. BN80927 shows high efficiency in vivo in tumor
      xenograft studies using human androgen-independent prostate tumors PC3 and DU145.
      Altogether, these data strongly support the clinical development of BN80927.

PMID- 15256468
TI  - Verapamil and its derivative trigger apoptosis through glutathione extrusion by
      multidrug resistance protein MRP1.
AB  - This study demonstrates that verapamil and a newly synthesized verapamil
      derivative, NMeOHI(2), behave as apoptogens in multidrug resistance protein 1
      (MRP1)-expressing cells. When treated with either verapamil or NMeOHI(2),
      surprisingly, baby hamster kidney-21 (BHK) cells transfected with human MRP1 were
      killed. Because parental BHK cells were not, as well as cells expressing an
      inactive (K1333L) MRP1 mutant, this indicated that cell death involved functional
      MRP1 transporter. Cell death was identified as apoptosis by using annexin V
      fluorescein labeling and was no longer observed in the presence of the caspase
      inhibitor Z-Val-Ala-Asp(OMe)-CH(2)F (Z-VAD-FMK). In vitro, both verapamil and its
      derivative inhibited leukotriene C4 transport by MRP1-enriched membrane vesicles
      in a competitive manner, with a K(i) of 48.6 microm for verapamil and 5.5 microm
      for NMeOHI(2,) and stimulated reduced glutathione (GSH) transport 3-fold and 9
      fold, respectively. Treatment of MRP1-expressing cells with either verapamil or
      the derivative quickly depleted intracellular GSH content with a strong decrease
      occurring in the first hour of treatment, which preceded cell death beginning at
      8-16 h. Furthermore, addition of GSH to the media efficiently prevented cell
      death. Therefore, verapamil and its derivative trigger apoptosis through
      stimulation of GSH extrusion mediated by MRP1. This new information on the
      mechanism of induced apoptosis of MDR cells may represent a novel approach in the
      selective treatment of MRP1-positive tumors.

PMID- 15256469
TI  - Synergistic suppression of microtubule dynamics by discodermolide and paclitaxel
      in non-small cell lung carcinoma cells.
AB  - Discodermolide is a new microtubule-targeted antimitotic drug in Phase I clinical
      trials that, like paclitaxel, stabilizes microtubule dynamics and enhances
      microtubule polymer mass in vitro and in cells. Despite their apparently similar
      binding sites on microtubules, discodermolide acts synergistically with
      paclitaxel to inhibit proliferation of A549 human lung cancer cells (L. Martello
      et al., Clin. Cancer Res., 6: 1978-1987, 2000). To understand their synergy, we
      examined the effects of the two drugs singly and in combination in A549 cells and
      found that, surprisingly, their antiproliferative synergy is related to their
      ability to synergistically inhibit microtubule dynamic instability and mitosis.
      The combination of discodermolide and paclitaxel at their antiproliferative
      IC(50)s (7 nm for discodermolide and 2 nm for paclitaxel) altered all of the
      parameters of dynamic instability synergistically except the time-based rescue
      frequency. For example, together the drugs inhibited overall microtubule
      dynamicity by 71%, but each drug individually inhibited dynamicity by only 24%,
      giving a combination index (CI) of 0.23. Discodermolide and paclitaxel also
      synergistically blocked cell cycle progression at G(2)-M (41, 9.6, and 16% for
      both drugs together, for discodermolide alone, and for paclitaxel alone,
      respectively; CI = 0.59), and they synergistically enhanced apoptosis (CI =
      0.85). Microtubules are unique receptors for drugs. The results suggest that
      ligands that bind to large numbers of binding sites on an individual microtubule
      can interact in a poorly understood manner to synergistically suppress
      microtubule dynamic instability and inhibit both mitosis and cell proliferation,
      with important consequences for combination clinical therapy with microtubule
      targeted drugs.

PMID- 15256470
TI  - Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring
      antitumor immunity.
AB  - A naturally occurring human antibody potentiates dendritic cell function on cross
      linking B7-DC (PD-L2), supporting robust T-cell responses in vitro. Moreover,
      treatment of dendritic cells with B7-DC cross-linking antibody resulted in
      secretion of interleukin-12, suggesting a TH1 polarization of this response. Here
      we show an in vivo immunotherapeutic effect of this B7-DC cross-linking antibody
      using a poorly immunogenic B16 melanoma tumor model. Treatment of mice
      systemically with antibody at the time of tumor cell engraftment prevented tumor
      growth in a CD4 and CD8 T-cell-dependent manner. The protective effect of B7-DC
      cross-linking antibody treatment was independent of endogenous antibody
      responses. Tumor-specific CTL precursors could be isolated from lymph nodes
      draining the tumor site in animals treated with B7-DC cross-linking antibody, but
      not from those treated with isotype control antibodies. The elicited antitumor
      responses in vivo were specific and long-lasting. More strikingly, treatment of
      mice with B7-DC cross-linking antibody after the tumors were established in the
      lungs resulted in protection in a CD8-, perforin-, and granzyme B-dependent
      fashion. Depletion of natural killer cells did not block the effects of treatment
      with B7-DC cross-linking antibody. Together, these findings demonstrate that
      cross-linking B7-DC with the human IgM antibody sHIgM12 can induce a protective
      immune response against a weakly antigenic experimental tumor and therefore has
      potential as a novel immunotherapeutic approach for treating cancer.

PMID- 15256471
TI  - Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific,
      cytotoxic T-cells in patients with malignant glioma.
AB  - The primary goal of this Phase I study was to assess the safety and bioactivity
      of tumor lysate-pulsed dendritic cell (DC) vaccination to treat patients with
      glioblastoma multiforme and anaplastic astrocytoma. Adverse events, survival, and
      cytotoxicity against autologous tumor and tumor-associated antigens were
      measured. Fourteen patients were thrice vaccinated 2 weeks apart with autologous
      DCs pulsed with tumor lysate. Peripheral blood mononuclear cells were
      differentiated into phenotypically and functionally confirmed DCs. Vaccination
      with tumor lysate-pulsed DCs was safe, and no evidence of autoimmune disease was
      noted. Ten patients were tested for the development of cytotoxicity through a
      quantitative PCR-based assay. Six of 10 patients demonstrated robust systemic
      cytotoxicity as demonstrated by IFN-gamma expression by peripheral blood
      mononuclear cells in response to tumor lysate after vaccination. Using HLA
      restricted tetramer staining, we identified a significant expansion in CD8+
      antigen-specific T-cell clones against one or more of tumor-associated antigens
      MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients. A
      significant CD8+ T-cell infiltrate was noted intratumorally in three of six
      patients who underwent reoperation. The median survival for patients with
      recurrent glioblastoma multiforme in this study (n = 8) was 133 weeks. This Phase
      I study demonstrated the feasibility, safety, and bioactivity of an autologous
      tumor lysate-pulsed DC vaccine for patients with malignant glioma. We demonstrate
      for the first time the ability of an active immunotherapy strategy to generate
      antigen-specific cytotoxicity in brain tumor patients.

PMID- 15256472
TI  - HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by
      cytotoxic T cells.
AB  - It has recently been demonstrated that malignant glioma cells express certain
      known tumor-associated antigens, such as HER-2, gp100, and MAGE-1. To further
      determine the possible utilization of these antigens for glioma immunotherapy and
      as surrogate markers for specific tumor antigen cytotoxicity, we characterized
      the presence of mRNA and protein expression in 43 primary glioblastoma multiforme
      (GBM) cell lines and 7 established human GBM cell lines. HER-2, gp100, and MAGE-1
      mRNA expression was detected in 81.4%, 46.5%, and 39.5% of the GBM primary cell
      lines, respectively. Using immunoreactive staining analysis by flow cytometry,
      HER-2, gp100, and MAGE-1 protein expression was detected in 76%, 45%, and 38% of
      the GBM primary cell lines, respectively. HLA-A1-restricted epitope specific for
      MAGE-1 peptide (EADPTGHSY) CTL clone B07 and HLA-A2-restricted epitope specific
      for HER-2 peptide (KIFGSLAFL) CTL clone A05 and gp100 peptide (ITDQVPFSV) CTL
      clone CK3H6 were used in this study. The specificity of CTL clone was verified by
      HLA/peptide tetramer staining. Three CTL clones could efficiently recognize GBM
      tumor cells in an antigen-specific and MHC class I-restricted manner. IFN-gamma
      treatment can dramatically increase MHC class I expression of GBM tumor cells and
      significantly increase CTL recognition of tumor cells. Treatment with the DNA
      hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA
      expression of MAGE-1 and epitope presentation by autologous MHC. These data
      indicate that HER-2, gp100, and MAGE-1 could be used as tumor antigen targets for
      surrogate assays for antigen-specific CTLs or to develop antigen-specific active
      immunotherapy strategies for glioma patients.

PMID- 15256473
TI  - A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn
      carbohydrate antigen induces tumor-specific antibodies in nonhuman primates.
AB  - We recently developed an efficient strategy based on a fully synthetic
      dendrimeric carbohydrate display (multiple antigenic glycopeptide; MAG) to induce
      anticarbohydrate antibody responses for therapeutic vaccination against cancer.
      Here, we show the superior efficacy of the MAG strategy over the traditional
      keyhole limpet hemocyanin glycoconjugate to elicit an anticarbohydrate IgG
      response against the tumor-associated Tn antigen. We highlight the influence of
      the aglyconic carrier elements of such a tumor antigen for their recognition by
      the immune system. Finally, we additionally developed the MAG system by
      introducing promiscuous HLA-restricted T-helper epitopes and performed its
      immunological evaluation in nonhuman primates. MAG:Tn vaccines induced in all of
      the animals strong tumor-specific anti-Tn antibodies that can mediate antibody
      dependent cell cytotoxicity against human tumor. Therefore, the preclinical
      evaluation of the MAG:Tn vaccine demonstrates that it represents a safe and
      highly promising immunotherapeutic molecularly defined tool for targeting breast,
      colon, and prostate cancers that express the carbohydrate Tn antigen.

PMID- 15256474
TI  - Dendritic cells pulsed with an anti-idiotype antibody mimicking carcinoembryonic
      antigen (CEA) can reverse immunological tolerance to CEA and induce antitumor
      immunity in CEA transgenic mice.
AB  - In this report, we have studied the immunogenicity of the nominal antigen,
      carcinoembryonic antigen (CEA), and that of an anti-idiotype antibody, 3H1, which
      mimics CEA and can be used as a surrogate for CEA. We have demonstrated that
      immunization of CEA transgenic mice with bone marrow-derived mature dendritic
      cells (DC) loaded with anti-idiotype 3H1 or CEA could reverse CEA
      unresponsiveness and result in the induction of CEA-specific immune responses and
      the rejection of CEA-transfected MC-38 colon carcinoma cells, C15. Immunized mice
      splenocytes proliferated in an antigen-specific manner by a mechanism dependent
      on the functions of CD4, MHC II, B7-2, CD40, CD28, and CD25. However, immune
      splenic lymphocytes isolated from 3H1-DC-vaccinated mice when stimulated in vitro
      with 3H1 or CEA secreted significantly higher levels of Th1 cytokines than did
      CEA-DC vaccinated mice. DC vaccination also induced antigen-specific effector
      CD8+ T cells capable of expressing interleukin-2, IFN-gamma, and tumor necrosis
      factor (TNF)-alpha and displayed cytotoxic activity against C15 cells in an MHC
      class I-restricted manner. 3H1-DC vaccination resulted in augmented CTL responses
      and the elevated expression of CD69, CD25, and CD28 on CD8(+) CTLs. The immune
      responses developed in 3H1-DC-immunized mice resulted in rejection of C15 tumor
      cells in nearly 100% of experimental mice, whereas only 40% of experimental mice
      immunized with CEA-DC were protected from C15 tumor growth. These findings
      suggest that under the experimental conditions used, 3H1-DC vaccination was
      better than CEA-DC vaccination in breaking immune tolerance to CEA and inducing
      protective antitumor immune responses in this murine model transgenic for human
      CEA.

PMID- 15256475
TI  - Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates activation of cigarette
      smoke-induced nuclear factor (NF)-kappaB by suppressing activation of
      IkappaBalpha kinase in human non-small cell lung carcinoma: correlation with
      suppression of cyclin D1, COX-2, and matrix metalloproteinase-9.
AB  - Cigarette smoke (CS) has been linked to cardiovascular, pulmonary, and malignant
      diseases. CS-associated malignancies including cancers of the larynx, oral
      cavity, and pharynx, esophagus, pancreas, kidney, bladder, and lung; all are
      known to overexpress the nuclear factor-kappaB (NF-kappaB)-regulated gene
      products cyclin D1, cyclooxygenase (COX)-2, and matrix metalloprotease-9. Whether
      the COX-2 inhibitor, celecoxib, approved for the treatment of colon
      carcinogenesis and rheumatoid arthritis, affects CS-induced NF-kappaB activation
      is not known, although the role of NF-kappaB in regulation of apoptosis,
      angiogenesis, carcinogenesis, and inflammation is established. In our study, in
      which we examined DNA binding of NF-kappaB in human lung adenocarcinoma H1299
      cells, we found that cigarette smoke condensate (CSC)-induced NF-kappaB
      activation was persistent up to 24 h, and celecoxib suppressed CSC-induced NF
      kappaB activation. Celecoxib was effective even when administered 12 h after CSC
      treatment. This effect, however, was not cell type-specific. The activation of
      inhibitory subunit of NF-kappaB kinase (IkappaB), as examined by immunocomplex
      kinase assay, IkappaB phosphorylation, and IkappaB degradation was also
      inhibited. Celecoxib also abrogated CSC-induced p65 phosphorylation and nuclear
      translocation and NF-kappaB-dependent reporter gene expression. CSC-induced NF
      kappaB reporter activity induced by NF-kappaB inducing kinase and IkappaB alpha
      kinase but not that activated by p65 was also blocked by celecoxib. CSC induced
      the expression of NF-kappaB-regulated proteins, COX-2, cyclin D1, and matrix
      metalloproteinase-9, and celecoxib abolished the induction of all three. The COX
      2 promoter that is regulated by NF-kappaB was activated by CSC, and celecoxib
      suppressed its activation. Overall, our results suggest that chemopreventive
      effects of celecoxib may in part be mediated through suppression of NF-kappaB and
      NF-kappaB-regulated gene expression, which may contribute to its ability to
      suppress inflammation, proliferation, and angiogenesis.

PMID- 15256476
TI  - Breast cancer risk and the DNA double-strand break end-joining capacity of
      nonhomologous end-joining genes are affected by BRCA1.
AB  - A tumorigenic role of the nonhomologous end-joining (NHEJ) pathway for the repair
      of DNA double-strand breaks (DSBs) has been suggested by the finding of a
      significant association between increased breast cancer risk and a cooperative
      effect of single nucleotide polymorphisms (SNPs) in NHEJ genes. However, the lack
      of an association between hereditary breast cancer and defective NHEJ genes
      prevents conclusions from being drawn about a link between NHEJ and breast cancer
      development. Recently, BRCA1-deficient mouse embryonic fibroblasts were found to
      have significantly reduced NHEJ activity, suggesting an accessory role of BRCA1
      in NHEJ. The present study was performed to confirm this observation in human
      breast cancer cell lines and to examine whether the interaction between BRCA1 and
      NHEJ was of tumorigenic significance. Support for this hypothesis came from the
      findings that (a) a case-control study (469 breast cancer patients and 740
      healthy controls) showed that the breast cancer risk associated with high-risk
      genotypes of NHEJ genes was significantly modified by the BRCA1 genotype. A
      significant increase in the cancer risk associated either with harboring one
      additional putative high-risk NHEJ genotype or with the joint effect of having
      reproductive risk factors (reflected by an interval of > or =12 years between
      menarche and first full-term pregnancy) and a higher number of high-risk
      genotypes of the NHEJ genes was only seen in women with at least one variant
      BRCA1 allele (i.e., the Glu/Gly or Gly/Gly forms of BRCA1 Glu(1038)Gly); and (b)
      a phenotype-based study measuring in vitro and in vivo NHEJ capacity showed that
      the precise end-joining capacity was different in breast cancer cell lines with
      different BRCA1 statuses being higher in BRCA1-expressing MCF-7 cells than in
      HCC1937 cells (defective BRCA1 expression). Furthermore, this end-joining
      capacity was decreased in MCF-7 cells in which BRCA1 expression was blocked using
      small interfering RNA and increased in HCC1937 transfected with full-length
      BRCA1. Because BRCA1 is a well-documented breast cancer susceptibility gene, this
      association between NHEJ and BRCA1 not only suggests a role of BRCA1 in NHEJ but
      also provides essential support for the tumorigenic contribution of NHEJ in
      breast cancer development.

PMID- 15256477
TI  - Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in
      the epidermis of p53 and Bax knockout mice.
AB  - Shaved male or female p53(-/-) C57BL/6J mice and their wild-type littermates were
      irradiated once with UVB (60 mJ/cm(2)). The UVB-induced increase in apoptotic
      sunburn cells in p53(-/-) mice at 6-10 h after exposure to UVB was only 10-30% of
      that observed after treatment of p53(+/+) mice with UVB. Topical applications of
      caffeine immediately after UVB irradiation in female p53(+/+) or p53(-/-) mice
      enhanced the UVB-induced increase in apoptotic sunburn cells 6 h later by 127%
      and 563%, respectively. In another study, shaved female Bax(-/-) C57BL/6J mice
      and their wild-type littermates were irradiated once with UVB (60 mJ/cm(2)). The
      UVB-induced increase in apoptotic sunburn cells in Bax(-/-) mice at 6 h after
      exposure to UVB was only 14% of that observed after treatment of Bax(+/+) mice
      with UVB. Topical application of caffeine immediately after irradiation of
      Bax(+/+) or Bax(-/-) mice with UVB enhanced the UVB-induced increases in
      apoptotic sunburn cells at 6 h by 214% and 467%, respectively, and topical
      application of caffeine immediately after irradiation of Bax(+/+) or Bax(-/-)
      mice with UVB enhanced the UVB-induced increase in caspase 3 (active form)
      positive cells at 6 h by 253% and 750%, respectively. The results indicate that
      UVB-induced increases in apoptosis in the epidermis of wild-type mice are
      predominantly (but not entirely) by p53- and Bax-dependent pathways and that
      topical application of caffeine can enhance UVB-induced increases in apoptosis by
      p53- and Bax-independent pathways.

PMID- 15256478
TI  - Minocycline exerts multiple inhibitory effects on vascular endothelial growth
      factor-induced smooth muscle cell migration: the role of ERK1/2, PI3K, and matrix
      metalloproteinases.
AB  - Widely used tetracycline antibiotics affect many cellular functions relevant to
      human vascular disease including cell proliferation, migration, and matrix
      remodeling. We examined whether minocycline inhibited human aortic smooth muscle
      cell (HASMC) migration induced by vascular endothelial growth factor (VEGF).
      After the establishment of an optimal dose, minocycline treated HASMC were
      exposed to VEGF. HASMC migration, matrix metalloproteinase (MMP)-2 and MMP-9
      activities, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3
      kinase (PI3K) phosphorylation were determined by smooth muscle cell (SMC)
      invasion assay, real-time polymerase chain reaction, zymograms, and Western blot
      analysis, respectively. We demonstrated that VEGF and platelet-derived growth
      factor (PDGF)-induced SMC migration in a dose-dependent manner. MMP-9, but not
      MMP-2, mRNA was increased during VEGF stimulation. MMP-9 activity was increased
      from 1.5- to 2.5-fold in a dose-dependent manner (P<0.05). Both ERK1/2 and
      PI3K/AKt pathways were activated during VEGF-induced HASMCs migration. We then
      demonstrated that minocycline can inhibit VEGF-induced HASMC migration (P<0.05).
      The effects may be through the inhibition of MMP-9 mRNA transcription, protein
      activities and downregulation of ERK1/2 and PI3K/Akt pathway phosphorylation. Our
      results indicated that minocycline exerts multiple effects on VEGF-induced SMC
      migration, including inhibition of MMP-9 mRNA transcription and protein
      activities and downregulating ERK1/2 and PI3K signal pathways, suggesting
      minocycline may be a potentially therapeutic approach to inhibit disease process
      induced angiogenesis.

PMID- 15256480
TI  - Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+
      channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic
      pulmonary hypertension.
AB  - Chronic hypoxic pulmonary hypertension is associated with profound vascular
      remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth
      muscle cells (PASMCs). Recent studies show that transient receptor potential
      (TRPC) genes, which encode store-operated and receptor-operated cation channels,
      play important roles in Ca(2+) regulation and cell proliferation. However, the
      influence of chronic hypoxia on TRPC channels has not been determined. Here we
      compared TRPC expression, and store- and receptor-operated Ca(2+) entries in
      PASMCs of normoxic and chronic hypoxic rats. Reverse-transcription polymerase
      chain reaction (RT-PCR), Western blot, and immunostaining showed consistently
      that TRPC1, TRPC3, and TRPC6 were expressed in intralobar pulmonary arteries
      (PAs) and PASMCs. Application of 1-oleoyl-2-acetyl-sn-glycerol (OAG) to directly
      activate receptor-operated channels, or thapsigargin to deplete Ca(2+) stores,
      caused dramatic increase in cation entry measured by Mn(2+) quenching of fura-2
      and by Ca(2+) transients. OAG-induced responses were approximately 700-fold more
      resistant to La(3+) inhibition than thapsigargin-induced responses. siRNA
      knockdown of TRPC1 and TRPC6 specifically attenuated thapsigargin- and OAG
      induced cation entries, respectively, indicating that TRPC1 mediates store
      operated entry and TRPC6 mediates receptor-operated entry. In hypoxic PAs, there
      were 2- to 3-fold increases in TRPC1 and TRPC6 expression. They were accompanied
      by significant increases in basal, OAG-induced, and thapsigargin-induced cation
      entries in hypoxic PASMCs. Moreover, removal of Ca(2+) or inhibition of store
      operated Ca(2+) entry with La(3+) and SK&F-96365 reversed the elevated basal
      [Ca(2+)](i) in PASMCs and vascular tone in PAs of chronic hypoxic animals, but
      nifedipine had minimal effects. Our results for the first time to our knowledge
      show that both store- and receptor-operated channels of PASMCs are upregulated by
      chronic hypoxia and contribute to the enhanced vascular tone in hypoxic pulmonary
      hypertension.

PMID- 15256479
TI  - L-type voltage-gated Ca2+ channels modulate expression of smooth muscle
      differentiation marker genes via a rho kinase/myocardin/SRF-dependent mechanism.
AB  - Vascular smooth muscle cell (SMC) contraction is mediated in part by calcium
      influx through L-type voltage-gated Ca2+ channels (VGCC) and activation of the
      RhoA/Rho kinase (ROK) signaling cascade. We tested the hypothesis that Ca2+
      influx through VGCCs regulates SMC differentiation marker expression and that
      these effects are dependent on RhoA/ROK signaling. Depolarization-induced
      activation of VGCCs resulted in a nifedipine-sensitive increase in endogenous
      smooth muscle myosin heavy chain (SMMHC) and SM alpha-actin expression and CArG
      dependent promoter activity, as well as c-fos promoter activity. The ROK
      inhibitor, Y-27632, prevented depolarization-induced increase in SMMHC/SM alpha
      actin but had no effect on c-fos expression. Conversely, the Ca2+/calmodulin
      dependent kinase inhibitor, KN93, prevented depolarization-induced increases in c
      fos expression with no effect on SMMHC/SM alpha-actin. Depolarization increased
      expression of myocardin, a coactivator of SRF that mediates CArG-dependent
      transcription of SMC marker gene promoters containing paired CArG cis regulatory
      elements (SMMHC/SM alpha-actin). Both nifedipine and Y-27632 prevented the
      depolarization-induced increase in myocardin expression. Moreover, short
      interfering RNA (siRNA) specific for myocardin attenuated depolarization-induced
      SMMHC/SM alpha-actin transcription. Chromatin immunoprecipitation (ChIP) assays
      revealed that depolarization increased SRF enrichment of the CArG regions in the
      SMMHC, SM alpha-actin, and c-fos promoters in intact chromatin. Whereas Y-27632
      decreased basal and depolarization-induced SRF enrichment in the SMMHC/SM alpha
      actin promoter regions, it had no effect of SRF enrichment of c-fos. Taken
      together, these results provide evidence for a novel mechanism whereby Ca2+
      influx via VGCCs stimulates expression of SMC differentiation marker genes
      through mechanisms that are dependent on ROK, myocardin, and increased binding of
      SRF to CArG cis regulatory elements.

PMID- 15256481
TI  - Actin cytoskeleton organization and posttranscriptional regulation of endothelial
      nitric oxide synthase during cell growth.
AB  - Posttranscriptional regulation of endothelial nitric oxide synthase (eNOS)
      expression is an important mechanism by which endothelial cells respond to
      various physiological and pathophysiological stimuli. Previously, we showed that
      eNOS expression was dramatically altered by the state of cell growth and that the
      mechanism responsible for this regulation was entirely posttranscriptional,
      occurring via changes in eNOS mRNA stability. The present study identifies a role
      for actin cytoskeleton organization in the posttranscriptional regulation of eNOS
      during cell growth and examines the relationship between the state of actin
      polymerization and eNOS expression. We identified monomeric actin (globular [G]
      actin) as the major component of a 51-kDa ribonucleoprotein that binds to the
      eNOS mRNA 3' untranslated region in UV-crosslinking analysis. Binding activity of
      the ribonucleoprotein complex correlated with the relative concentration of G
      actin versus filamentous actin (F-actin). ENOS transcripts colocalized with
      cytoplasmic G-actin in cells subjected to fluorescence in situ hybridization and
      G-actin fluorescence staining. In subcellular fractionation studies, eNOS
      transcripts were enriched in the free polysomal fraction of nonproliferating
      cells and enriched in the cell matrix-associated polysomal fraction of
      proliferating cells. Furthermore, an inverse relationship between the
      concentration of G-actin and eNOS expression was observed in endothelial cells
      subjected to pharmacological alteration of their cytoskeleton; lower G/F-actin
      ratios correlated with increased eNOS expression. Our findings provide some
      insight into how endothelial cells may use the dynamic organization of the actin
      cytoskeleton to regulate expression of an enzyme that is crucial to vascular
      homeostasis.

PMID- 15256482
TI  - Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves
      mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway.
AB  - Human CYP2J2 is abundant in heart and active in the biosynthesis of
      epoxyeicosatrienoic acids (EETs); however, the functional role of this P450 and
      its eicosanoid products in the heart remains unknown. Transgenic mice with
      cardiomyocyte-specific overexpression of CYP2J2 were generated. CYP2J2 transgenic
      (Tr) mice have normal heart anatomy and basal contractile function. CYP2J2 Tr
      hearts have improved recovery of left ventricular developed pressure (LVDP)
      compared with wild-type (WT) hearts after 20 minutes ischemia and 40 minutes
      reperfusion. Perfusion with the selective P450 epoxygenase inhibitor N
      methylsulphonyl-6-(2-proparglyloxyphenyl)hexanamide (MS-PPOH) for 20 minutes
      before ischemia results in reduced postischemic LVDP recovery in WT hearts and
      abolishes the improved postischemic LVDP recovery in CYP2J2 Tr hearts. Perfusion
      with the ATP-sensitive K(+) channel (K(ATP)) inhibitor glibenclamide (GLIB) or
      the mitochondrial K(ATP) (mitoK(ATP)) inhibitor 5-hydroxydecanoate (5-HD) for 20
      minutes before ischemia abolishes the cardioprotective effects of CYP2J2
      overexpression. Flavoprotein fluorescence, a marker of mitoK(ATP) activity, is
      higher in cardiomyocytes from CYP2J2 Tr versus WT mice. Moreover, CYP2J2-derived
      EETs (1 to 5 micromol/L) increase flavoprotein fluorescence in WT cardiomyocytes.
      CYP2J2 Tr mice exhibit increased expression of phospho-p42/p44 mitogen-activated
      protein kinase (MAPK) after ischemia, and addition of the p42/p44 MAPK kinase
      (MEK) inhibitor PD98059 during reperfusion abolishes the cardioprotective effects
      of CYP2J2 overexpression. Together, these data suggest that CYP2J2-derived
      metabolites are cardioprotective after ischemia, and the mechanism for this
      cardioprotection involves activation of mitoK(ATP) and p42/p44 MAPK.

PMID- 15256483
TI  - Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast
      cancer risk in post-menopausal Chinese women in Singapore.
AB  - We have previously found marine n-3 fatty acids to be inversely related to post
      menopausal breast cancer in Chinese women from Singapore. Post-menopausal women
      with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a
      statistically significant reduction in risk of breast cancer after adjustment for
      potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) =
      0.50, 0.87]. Experimental studies have demonstrated a direct role for the
      peroxidation products of marine n-3 fatty acids in breast cancer protection.
      There is a suggestion that the glutathione S-transferases (GSTs) may be major
      catalysts in the elimination of these beneficial by-products. Therefore, we
      hypothesized that individuals possessing the low activity genotypes of GSTM1,
      GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes,
      respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer
      association than their high activity counterparts. The Singapore Chinese Health
      Study is a prospective investigation involving 35,298 middle-aged and older
      women, who were enrolled between April 1993 and December 1998. In this case
      control analysis, nested within the Singapore Chinese Health Study, we compared
      258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer
      risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype
      was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71,
      95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1
      positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer
      relationships were observed in either pre-menopausal or post-menopausal women at
      baseline. However, post-menopausal women possessing the combined GSTM1 null and
      GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after
      adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14,
      0.94). A similar relationship was observed among women with the combined GSTT1
      null and GSTP1 AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).

PMID- 15256484
TI  - Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human
      colon cancer cells.
AB  - Curcumin, the major pigment of the dietary spice turmeric has the potential for
      chemoprevention by promotion of apoptosis. Mitogen-activated protein kinase
      (MAPK) and NF-kappa B (NFkappaB) signalling cascades are thought to regulate
      apoptosis and cell survival. While curcumin inhibits NFkappaB, its effects upon
      the MAPK pathways are unclear. This study investigates curcumin effects upon MAPK
      signalling and apoptosis in HCT116 cells. Here we report that curcumin time- and
      dose-dependent induction of apoptosis were accompanied by sustained
      phosphorylation and activation of c-jun N-terminal kinase (JNK) and p38 MAPK as
      well as inhibition of constitutive NFkappaB transcriptional activity. Curcumin
      treatment also induced JNK-dependent sustained phosphorylation of c-jun and
      stimulation of AP-1 transcriptional activity. Curcumin-mediated c-jun
      phosphorylation and apoptosis were reduced by treatment with the JNK-specific
      inhibitor SP600125. Conversely, the p38-specific inhibitor SB203580 had no effect
      upon curcumin-induced apoptosis. Curcumin treatment had no effect on the activity
      of extracellular signal-regulated protein kinase (ERK). Taken together, our data
      show for the first time that JNK, but not p38 or ERK signalling, plays an
      important role in curcumin-mediated apoptosis in human colon cancer cells that
      may underlie its chemopreventive effects.

PMID- 15256485
TI  - Suppressed NF-kappaB and sustained JNK activation contribute to the sensitization
      effect of parthenolide to TNF-alpha-induced apoptosis in human cancer cells.
AB  - Parthenolide (PN) is the main sesquiterpene lactone found in feverfew with potent
      anti-inflammatory function. The anticancer property of PN has been demonstrated
      in both in vitro cell culture and in vivo animal model, while the molecular
      mechanisms remain to be further elucidated. In the present study, we evaluated
      the involvement of nuclear transcription factor-kappaB (NF-kappaB) and c-Jun N
      terminal kinase (JNK) in the anticancer activity of PN by examining the
      sensitization effect of PN on tumor necrosis factor (TNF)-alpha-induced apoptosis
      in human cancer cells. Pre-treatment with PN greatly sensitized various human
      cancer cells to TNF-alpha-induced apoptosis. Such sensitization is closely
      associated with the inhibitory effect of PN on TNF-alpha-mediated NF-kappaB
      activation. Our study revealed a new mechanism that PN inhibits TNF-alpha
      mediated NF-kappaB activation via disrupting the recruitment of the IkappaB
      kinases (IKK) complex to TNF receptor, which then blocked the subsequent
      signaling events including IKK kinase activation, IkappaBalpha degradation, p65
      nuclear translocation, DNA binding and transactivation. Moreover, PN also
      markedly enhanced and sustained TNF-alpha-mediated JNK activation. A specific JNK
      inhibitor (SP600125), as well as over-expression of dominant-negative forms of
      JNK1 and JNK2 abolished the sensitization effect of PN on TNF-alpha-induced
      apoptosis. It is thus believed that suppressed NF-kappaB activation and sustained
      JNK activation contribute to the sensitization effect of PN to TNF-alpha-mediated
      cell death in human cancer cells.

PMID- 15256486
TI  - Regulation of multimers via truncated isoforms: a novel mechanism to control
      nitric-oxide signaling.
AB  - Nitric oxide (NO) is an essential regulator of Drosophila development and
      physiology. We describe a novel mode of regulation of NO synthase (NOS) function
      that uses endogenously produced truncated protein isoforms of Drosophila NOS
      (DNOS). These isoforms inhibit NOS enzymatic activity in vitro and in vivo,
      reflecting their ability to form complexes with the full-length DNOS protein
      (DNOS1). Truncated isoforms suppress the antiproliferative action of DNOS1 in the
      eye imaginal disc by impacting the retinoblastoma-dependent pathway, yielding
      hyperproliferative phenotypes in pupae and adult flies. Our results indicate that
      endogenous products of the dNOS locus act as dominant negative regulators of NOS
      activity during Drosophila development.

PMID- 15256487
TI  - Drosophila atm/telomere fusion is required for telomeric localization of HP1 and
      telomere position effect.
AB  - Terminal deletions of Drosophila chromosomes can be stably protected from end-to
      end fusion despite the absence of all telomere-associated sequences. The sequence
      independent protection of these telomeres suggests that recognition of chromosome
      ends might contribute to the epigenetic protection of telomeres. In mammals,
      Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through
      an unknown, telomerase-independent mechanism to regulate telomere length and
      protection. We demonstrate that the Drosophila homolog of ATM is encoded by the
      telomere fusion (tefu) gene. In the absence of ATM, telomere fusions occur even
      though telomere-specific Het-A sequences are still present. High levels of
      spontaneous apoptosis are observed in ATM-deficient tissues, indicating that
      telomere dysfunction induces apoptosis in Drosophila. Suppression of this
      apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through
      a DNA damage-response mechanism. Loss of ATM reduces the levels of
      heterochromatin protein 1 (HP1) at telomeres and suppresses telomere position
      effect. We propose that recognition of chromosome ends by ATM prevents telomere
      fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres.

PMID- 15256488
TI  - Metabolic adaptations in skeletal muscle during lactation: complementary
      deoxyribonucleic acid microarray and real-time polymerase chain reaction analysis
      of gene expression.
AB  - Lactation and fasting are two physiological models characterized by negative
      energy balance. Our previous studies demonstrated that uncoupling protein (UCP) 3
      expression in skeletal muscle was down-regulated during lactation and up
      regulated during fasting. The present studies used cDNA microarray and real-time
      PCR to perform a systems and comparative analysis in gene expression in skeletal
      muscle under conditions of negative energy balance. Gastrocnemius skeletal muscle
      RNA pools were generated from the following groups of rats: cycling diestrous
      females, cycling females with 48 h of fasting, lactation, and lactation + leptin.
      Of those known genes studied, 35 genes were up-regulated and 49 were down
      regulated during lactation. Leptin treatment during lactation reversed the
      differential regulation of about 80% of these genes, demonstrating the importance
      of the leptin suppression to the changes in skeletal muscle metabolism. GenMAPP
      analysis revealed a coordinated regulation at key steps in
      glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and lipid metabolism,
      indicating an increased rate of lactate production through glycolysis and reduced
      fatty acid degradation in skeletal muscle during lactation. Particular interest
      was paid to those genes that changed in a similar manner to UCP3 mRNA. Many of
      these genes that were decreased during lactation and increased during fasting are
      involved in fatty acid degradation and transport, including acyl-coenzyme A
      dehydrogenase for medium chain fatty acid, carnitine palmitoyltransferase 1, and
      fatty acid translocase. The current studies provide a basis for investigating the
      mechanisms underlying metabolic adaptations during lactation and fasting and
      highlight the importance of UCP3 in lipid metabolism.

PMID- 15256489
TI  - Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin
      induced feeding.
AB  - Plasma levels of the orexigenic hormone, ghrelin, decrease rapidly on nutrient
      ingestion and yet are paradoxically elevated in rats with hyperphagia induced by
      streptozotocin-induced diabetes (STZ-DM). In the current work, we investigated
      the mechanisms underlying the relationships among uncontrolled diabetes, food
      intake, and plasma ghrelin concentrations in an effort to clarify whether
      increased ghrelin signaling contributes to diabetic hyperphagia. Whereas food
      intake did not increase until d 3 after STZ administration, plasma ghrelin levels
      were increased by more than 2-fold (P < 0.05) on d 1. As hyperphagia developed,
      however, plasma ghrelin levels declined steadily. Because this reduction of
      plasma ghrelin levels was reversed by matching food intake of STZ-DM rats to that
      of nondiabetic controls, our results demonstrated that the effect of uncontrolled
      diabetes to increase plasma ghrelin levels is partially offset by hyperphagic
      feeding. In addition, we found that although intragastric nutrient infusion
      rapidly and comparably decreased plasma ghrelin levels in both groups (by 46-49%;
      P < 0.05), this effect was short lived in STZ-DM rats relative to nondiabetic
      controls (60 min vs. 120 min; P < 0.05). We further demonstrated that in rats
      with STZ-DM, food intake increased by 357% (P < 0.05) in response to
      intracerebroventricular administration of ghrelin at a dose that was subthreshold
      for feeding effects in nondiabetic controls. Collectively, these findings
      demonstrate that uncontrolled diabetes increases both circulating ghrelin levels
      and behavioral sensitivity to ghrelin. Although plasma ghrelin levels fall in
      response to hyperphagic feeding, these findings support the hypothesis that
      increased ghrelin signaling contributes to the pathogenesis of diabetic
      hyperphagia.

PMID- 15256490
TI  - Proinflammatory cytokine impairment of insulin-like growth factor I-induced
      protein synthesis in skeletal muscle myoblasts requires ceramide.
AB  - GH and IGF-I control over 80% of postnatal growth. We recently established that
      TNFalpha impairs the ability of IGF-I to increase protein synthesis and promote
      expression of myogenin in myoblasts. Here we extend these results by showing that
      ceramide, a second messenger in both TNFalpha and IL-1beta receptor signaling
      pathways, is a key downstream sphingosine-based lipid that leads to IGF-I
      resistance. A cell-permeable ceramide analog, C2-ceramide, inhibits IGF-I-induced
      protein synthesis by 65% and blocks the ability of IGF-I to increase expression
      of two key myogenic factors, myogenin and MyoD. Identical results were obtained
      with both TNFalpha and IL-1beta (1 ng/ml). Consistent with these data, neutral
      sphingomyelinase (N-SMase), an enzyme that catalyzes formation of ceramide from
      sphingomyelin, blocks IGF-I-induced protein synthesis and expression of both
      myogenin and MyoD. The possibility that cytokine-induced ceramide production is
      required for disruption of IGF-I biologic activity was confirmed by treating
      C2C12 myoblasts with inhibitors of all three ceramide-generating pathways. A N
      SMase inhibitor, glutathione, as well as an acidic sphingomyelinase (A-SMase)
      inhibitor, D609, reverse the cytokine inhibition of IGF-I-induced protein
      synthesis by 80% and 45%, respectively. Likewise, an inhibitor of de novo
      ceramide synthesis, FB1, causes a 50% inhibition. Similarly, all three inhibitors
      significantly impair the ability of both TNFalpha and IL-1beta to suppress IGF-I
      driven expression of myogenin. These experiments establish that ceramide, derived
      both from sphingomyelin and de novo synthesis, is a key intermediate by which
      proinflammatory cytokines impair the ability of IGF-I to promote protein
      synthesis and expression of critical muscle-specific transcription factors.

PMID- 15256491
TI  - Thyroid hormone regulates oligodendrocyte accumulation in developing rat brain
      white matter tracts.
AB  - Thyroid hormone (TH) is necessary for normal axonal myelination. Myelin basic
      protein (MBP) is a structural protein essential for myelin function. In this
      study, we demonstrate that perinatal hypothyroidism regulates MBP mRNA levels via
      indirect mechanisms. We observed decreased MBP mRNA accumulation in the
      hypothyroid rat brain at postnatal (PN) d 10 and 50. Acute TH replacement did not
      rescue hypothyroid MBP mRNA levels at PN5, 10, or 50. TH is necessary for normal
      intrahemispheric commissure development including the anterior commissure (AC)
      and the corpus callosum (CC). We determined that perinatal hypothyroidism
      decreases AC area and cellularity in the developing rat brain by PN10 and 50. In
      the developing CC, hypothyroidism initially increases area and cellularity by
      PN5, but then ultimately decreases area and cellularity by PN50. MBP-expressing
      oligodendrocytes are a recognized target of TH and are responsible for
      myelination within intrahemispheric commissures. We found that hypothyroidism
      reduces the number of mature oligodendrocytes within both the AC and CC. This
      reduction is noted at PN5, 10, and 50 in the AC and by PN10 and 50 in the CC.
      Together, these data suggest that TH regulates MBP mRNA levels through indirect
      mechanisms. These data demonstrate the complex mechanisms whereby TH regulates
      myelination in the developing brain.

PMID- 15256492
TI  - Effect of Agouti-related protein in regulation of the hypothalamic-pituitary
      thyroid axis in the melanocortin 4 receptor knockout mouse.
AB  - Agouti-related protein (AGRP) is thought to be one of the neuropeptides mediating
      the effects of leptin on appetite and satiety. The central administration of AGRP
      not only stimulates food intake, but also inhibits the hypothalamic-pituitary
      thyroid axis (HPT) axis, closely replicating the central hypothyroid state
      induced by fasting. AGRP binds as an endogenous antagonist or inverse agonist of
      the central melanocortin receptors but has also been hypothesized to have
      melanocortin receptor-independent effects. Thus, we determined whether the
      central effects of AGRP on the HPT axis are altered in mice with selective
      deletion of the melanocortin 4 receptor (MC4-R). AGRP or artificial cerebrospinal
      fluid was administered daily into the lateral ventricle of adult, male MC4-R
      knockout and wild-type (WT) mice for 3 d. AGRP significantly increased the
      cumulative food intake and weight of white and brown adipose tissue, suppressed
      circulating levels of T(4) [control vs. AGRP in WT (microg/dl): 4.54 +/- 0.16 vs.
      3.87 +/- 21], and inhibited proTRH mRNA content in the hypothalamic
      paraventricular nucleus of WT mice (control vs. AGRP in WT (density units +/-
      sem): 4.65 +/- 0.50 vs. 2.47 +/- 0.17). In contrast, no significant effects of
      AGRP were observed in any of these parameters in the MC4-R knockout mice. These
      data suggest that AGRP signaling to TRH hypophysiotropic neurons in the
      paraventricular nucleus is primarily mediated by the MC4-R and therefore, binding
      to the MC3-R or other putative AGRP receptors may have only a minor role.

PMID- 15256493
TI  - Genetic targeting of relaxin and insulin-like factor 3 receptors in mice.
AB  - Relaxin (RLN) is a small peptide hormone that affects a variety of biological
      processes. Rln1 knockout mice exhibit abnormal nipple development, prolonged
      parturition, agerelated pulmonary fibrosis, and abnormalities in the testes and
      prostate. We describe here RLN receptor Lgr7-deficient mice. Mutant females have
      grossly underdeveloped nipples and are unable to feed their progeny. Some Lgr7-/-
      females were unable to deliver their pups. Histological analysis of Lgr7 mutant
      lung tissues demonstrates increased collagen accumulation and fibrosis
      surrounding the bronchioles and the vascular bundles, absent in wild-type
      animals. However, Lgr7-deficient males do not exhibit abnormalities in the testes
      or prostate as seen in Rln1 knockout mice. Lgr7-deficient females with additional
      deletion of Lgr8 (Great), another putative receptor for RLN, are fertile and have
      normal-sized litters. Double mutant males have normal-sized prostate and testes,
      suggesting that Lgr8 does not account for differences in Rln1-/- and Lgr7-/-
      phenotypes. Transgenic overexpression of Insl3, the cognate ligand for Lgr8, does
      not rescue the mutant phenotype of Lgr7-deficient female mice indicating
      nonoverlapping functions of the two receptors. Our data indicate that neither
      Insl3 nor Lgr8 contribute to the RLN signaling pathway. We conclude that the
      Insl3/Lgr8 and Rln1/Lgr7 actions do not overlap in vivo.

PMID- 15256494
TI  - Ghrelin degradation by serum and tissue homogenates: identification of the
      cleavage sites.
AB  - The endogenous ligand for the GH secretagogue receptor is ghrelin, a peptide
      recently purified from the stomach. Ghrelin is n-octanoylated on the Ser(3)
      residue, and this modification is essential for its interaction with the
      receptor. The degradation of ghrelin by rat and human serum, purified commercial
      enzymes, and tissues homogenates was analyzed by combining HPLC and mass
      spectrometry. In serum, ghrelin was desoctanoylated, without proteolysis. The
      desoctanoylation was significantly reduced by phenylmethylsulfonyl fluoride, a
      serine proteases and esterases inhibitor. In rat serum, the carboxylesterase
      inhibitor bis-p-nitrophenyl-phosphate totally inhibited ghrelin desoctanoylation,
      and a correlation was found between ghrelin desoctanoylation and carboxylesterase
      activity. Moreover, purified carboxylesterase degraded ghrelin. Thus,
      carboxylesterase could be responsible for ghrelin desoctanoylation in that
      species. In human serum, ghrelin desoctanoylation was partially inhibited by
      eserine salicylate and sodium fluoride, two butyrylcholinesterase inhibitors, but
      not by bis-p-nitrophenyl-phosphate and EDTA. Purified butyrylcholinesterase was
      able to degrade ghrelin, and there was a correlation between the
      butyrylcholinesterase and ghrelin desoctanoylation activities in human sera. This
      suggested that several esterases, including butyrylcholinesterase, contributed to
      ghrelin desoctanoylation in human serum. In contact with tissues homogenates,
      ghrelin was degraded by both desoctanoylation and N-terminal proteolysis. We
      identified five cleavage sites in ghrelin between residues -Ser(2)-(acyl)Ser(3)-
      (stomach and liver), -(acyl?)Ser(3)-Phe(4)- (stomach, liver, and kidney), -Phe(4)
      Leu(5)- (stomach and kidney), -Leu(5)-Ser(6)- and -Pro(7)-Glu(8)- (kidney). In
      all cases, the resulting fragments were biologically inactive.

PMID- 15256495
TI  - Estrogen modulates microglial inflammatory mediator production via interactions
      with estrogen receptor beta.
AB  - Estrogens are well known to exert antiinflammatory effects outside the central
      nervous system (CNS). They have also been shown to exert neuroprotective effects
      in the CNS after several types of injury, including neurodegeneration. However,
      the molecular mechanisms by which these effects occur remain unclear. Because
      microglial hyperactivation and their production of neurotoxins is associated with
      many types of brain injury for which estrogens are beneficial, we sought to
      investigate the ability of estrogen to modulate microglial function. Furthermore,
      because little is known regarding the role of each of the two known estrogen
      receptors (ERs) in microglia, our studies were designed to test the hypothesis
      that 17beta-estradiol (E(2)) exerts antiinflammatory effects in microglia,
      specifically via interactions with ERbeta. We tested this hypothesis using the
      murine microglial cell line BV-2, which naturally expresses only ERbeta. Our
      results indicate that not only does E(2) decrease lipopolysaccharide (LPS)
      stimulated nitric oxide (NO) production and inducible nitric oxide synthase
      (iNOS) expression, it also reduces the expression of cyclooxygenase-2, a target
      for estrogen that has not previously been reported for ERbeta. We also observed
      that LPS-stimulated TNFalpha mRNA was increased by estrogen. E(2) exerts these
      effects within 30 min compared with typical estrogen transcriptional responses.
      Tamoxifen and ICI 182,780 differentially blocked the inhibitory effects of E(2)
      on LPS-stimulated iNOS and cyclooxygenase-2. In addition, we show that E(2)
      alters LPS-stimulated MAPK pathway activation, supporting the idea that
      alterations in the MAPKs may be a potential mechanism by which ERbeta mediates
      decreased microglial activation.

PMID- 15256496
TI  - Identification of a novel apolipoprotein, ApoN, in ovarian follicular fluid.
AB  - A novel apolipoprotein, designated ApoN, has been identified in bovine ovarian
      follicular fluid using chromatographic purification methods, amino acid sequence
      analysis, molecular biology, and bioinformatics. The apolipoprotein is a
      hydrophobic 12-kDa protein processed from the C terminus of a 29-kDa precursor
      expressed in a number of tissues, including the ovary, testis, the anterior
      chamber of the eye, skeletal muscle, uterus, and liver. Bovine, porcine, and
      murine ApoN display significant homology at the amino acid level across the
      entire precursor sequence. Surprisingly, there appears to be no orthologous
      protein in the human, although an APON-like pseudogene is found on chromosome 12.
      The N-terminal fragment of the ApoN precursor shows significant homology with the
      N-terminal sequence of the precursor of the cholesterol transport regulatory
      protein ApoF, but the corresponding C-terminal sequences of ApoN and ApoF possess
      no homology. ApoN is present in the high-density lipoprotein fraction of bovine
      serum and both the high-density lipoprotein and low-density lipoprotein fractions
      of bovine follicular fluid and is found in several tissues that are associated
      with local immunological privilege. These data suggest that ApoN may play a role
      in steroidogenesis and/or immunoregulation in the gonads of nonhuman species, as
      well as similar roles in other tissues.

PMID- 15256497
TI  - Establishing neuronal circuitry: Hox genes make the connection.

PMID- 15256498
TI  - Dm-myb mutant lethality in Drosophila is dependent upon mip130: positive and
      negative regulation of DNA replication.
AB  - Gene amplification at the chorion loci in Drosophila ovarian follicle cells is a
      model for the developmental regulation of DNA replication. Previously, we showed
      that the Drosophila homolog of the Myb oncoprotein family (DmMyb) is tightly
      associated with four additional proteins and that DmMyb is required for this
      replication-mediated amplification. Here we used targeted mutagenesis to generate
      a mutant in the largest subunit of the DmMyb complex, the Aly and Lin-9 family
      member, Myb-interacting protein 130 (Mip130). We found that mip130 mutant females
      are sterile and display inappropriate bromodeoxyuridine (BrdU) incorporation
      throughout the follicle cell nuclei at stages undergoing gene amplification.
      Whereas mutations in Dm-myb are lethal, mutations in mip130 are viable.
      Surprisingly, Dm-myb mip130 double mutants are also viable and display the same
      phenotypes as mip130 mutants alone. This suggests that Mip130 activity without
      DmMyb counteraction may be responsible for the Dm-myb mutant lethality. RNA
      interference (RNAi) to selectively remove each DmMyb complex member revealed that
      DmMyb protein levels are dependent upon the presence of several of the complex
      members. Together, these data support a model in which DmMyb activates a
      repressive complex containing Mip130 into a complex competent to support
      replication at specific loci in a temporally and developmentally proscribed
      manner.

PMID- 15256499
TI  - A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth
      pathway in yeast.
AB  - Signaling molecules such as Cdc42 and mitogen-activated protein kinases (MAPKs)
      can function in multiple pathways in the same cell. Here, we propose one
      mechanism by which such factors may be directed to function in a particular
      pathway such that a specific response is elicited. Using genomic approaches, we
      identify a new component of the Cdc42- and MAPK-dependent signaling pathway that
      regulates filamentous growth (FG) in yeast. This factor, called Msb2, is a FG
      pathway-specific factor that promotes differential activation of the MAPK for the
      FG pathway, Kss1. Msb2 is localized to polarized sites on the cell surface and
      interacts with Cdc42 and with the osmosensor for the high osmolarity glycerol
      response (HOG) pathway, Sho1. Msb2 is glycosylated and is a member of the mucin
      family, proteins that in mammalian cells promote disease resistance and
      contribute to metastasis in cancer cells. Remarkably, loss of the mucin domain of
      Msb2 causes hyperactivity of the FG pathway, demonstrating an inhibitory role for
      mucin domains in MAPK pathway activation. Taken together, our data suggest that
      Msb2 is a signaling mucin that interacts with general components, such as Cdc42
      and Sho1, to promote their function in the FG pathway.

PMID- 15256500
TI  - Cdk1-Clb4 controls the interaction of astral microtubule plus ends with
      subdomains of the daughter cell cortex.
AB  - As in many polarized cells, spindle alignment in yeast is essential and cell
      cycle regulated. A key step that governs spindle alignment is the selective
      binding of the Kar9 protein to only one of the two spindle pole bodies (SPBs). It
      has been suggested that cyclin-dependent kinase Cdc28, in complex with cyclin
      Clb4, associates only with the SPB in the mother cell and so prevents Kar9
      binding to this SPB. However, here we show that the nonoverexpressed Clb4
      associates with the budward-directed SPB through Kar9. Cdc28-Clb4 then uses Kar9
      as a carrier to move from this SPB to the plus ends of astral microtubules, where
      Cdc28-Clb4 regulates the interactions between microtubule ends and subdomains of
      the bud cortex. In the absence of Cdc28-Clb4 activity (G1/S phase), astral
      microtubules interact with the bud tip in a manner dependent on actin, Myo2, and
      Kar9. Coincidentally with reaching the bud cortex in S phase, Cdc28-Clb4
      facilitates the dissociation of the microtubule bud tip interaction and their
      capture by the bud neck. This transition prevents the preanaphase spindle from
      becoming prematurely pulled into the bud. Thus, Cdc28-Clb4 facilitates spindle
      alignment by regulating the interaction of astral microtubules with subdomains of
      the bud cortex.

PMID- 15256501
TI  - Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and
      retrovirus budding.
AB  - The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes
      in yeast and mammals. We report a novel protein, Tal (Tsg101-associated ligase),
      whose RING finger is necessary for multiple monoubiquitylation of Tsg101.
      Bivalent binding of Tsg101 to a tandem tetrapeptide motif (PTAP) and to a central
      region of Tal is essential for Tal-mediated ubiquitylation of Tsg101. By studying
      endocytosis of the epidermal growth factor receptor and egress of the human
      immunodeficiency virus, we conclude that Tal regulates a Tsg101-associated
      complex responsible for the sorting of cargo into cytoplasm-containing vesicles
      that bud at the multivesicular body and at the plasma membrane.

PMID- 15256502
TI  - Differential gene regulation by the SRC family of coactivators.
AB  - SRCs (steroid receptor coactivators) are required for nuclear receptor-mediated
      transcription and are also implicated in the transcription initiation by other
      transcription factors, such as STATs and NFkappaB. Despite phenotypic
      manifestations in gene knockout mice for SRC-1, GRIP1, and AIB1 of the SRC
      (Steroid Receptor Coactivator) family indicating their differential roles in
      animal physiology, there is no clear evidence, at the molecular level, to support
      a functional specificity for these proteins. We demonstrated in this report that
      two species of SRC coactivators, either as AIB1:GRIP1 or as AIB1:SRC-1 are
      recruited, possibly through heterodimerization, on the promoter of genes that
      contain a classical hormone responsive element (HRE). In contrast, on non-HRE
      containing gene promoters, on which steroid receptors bind indirectly, either
      GRIP1 or SRC-1 is recruited as a monomer, depending on the cellular abundance of
      the protein. Typically, non-HRE-containing genes are early genes activated by
      steroid receptors, whereas HRE-containing genes are activated later. Our results
      also showed that SRC proteins contribute to the temporal regulation of gene
      transcription. In addition, our experiments revealed a positive correlation
      between AIB1/c-myc overexpression in ER+ breast carcinoma samples, suggesting a
      possible mechanism for AIB1 in breast cancer carcinogenesis.

PMID- 15256503
TI  - Topological domain structure of the Escherichia coli chromosome.
AB  - The circular chromosome of Escherichia coli is organized into independently
      supercoiled loops, or topological domains. We investigated the organization and
      size of these domains in vivo and in vitro. Using the expression of >300
      supercoiling-sensitive genes to gauge local chromosomal supercoiling, we
      quantitatively measured the spread of relaxation from double-strand breaks
      generated in vivo and thereby calculated the distance to the nearest domain
      boundary. In a complementary approach, we gently isolated chromosomes and
      examined the lengths of individual supercoiled loops by electron microscopy. The
      results from these two very different methods agree remarkably well. By comparing
      our results to Monte Carlo simulations of domain organization models, we conclude
      that domain barriers are not placed stably at fixed sites on the chromosome but
      instead are effectively randomly distributed. We find that domains are much
      smaller than previously reported, approximately 10 kb on average. We discuss the
      implications of these findings and present models for how domain barriers may be
      generated and displaced during the cell cycle in a stochastic fashion.

PMID- 15256504
TI  - Ectopic pregnancy is again on the increase. Recent trends in the incidence of
      ectopic pregnancies in France (1992-2002).
AB  - BACKGROUND: We aimed to assess the recent incidence trends of ectopic pregnancies
      (EP) in France (1992-2002). METHODS: A population-based register of all women
      aged 15-44 years with EP was set up in Auvergne (central France). We calculated
      rates of EP as a 'reproductive failure' or as a 'contraceptive failure',
      frequencies of exposure to the two main risk factors for EP (cigarette smoking
      and chlamydial infection) and contraceptive methods between 1992 and 2002.
      RESULTS: The overall EP rate decreased by 2%, from 96.4 per 100 000 women aged 15
      44 in 1992 to 95.3 per 100 000 in 2002. However, the rate of 'reproductive
      failure' EP increased by 17%, while the rate of 'contraceptive failure' EP,
      mostly intrauterine device failure, decreased by 29%. CONCLUSION: Appropriate
      analysis reveals that the rate of EP as reproductive failure is increasing again
      in France. This result is of interest for many European and North America
      countries where chlamydial infections or smoking or both are increasing in women
      of reproductive age. The rates of EP as contraceptive failure and of that as
      reproductive failure evolve differently in the population and should not be
      confused in epidemiological studies.

PMID- 15256505
TI  - Comparison of four fluorochromes for the detection of the inner mitochondrial
      membrane potential in human spermatozoa and their correlation with sperm
      motility.
AB  - BACKGROUND: Sperm motility evaluation is associated with fertility in IVF
      programmes. The visual estimation of sperm motility is extremely subjective.
      Hence, alternative methods are required. Among them, determination of
      mitochondrial membrane potential (Deltapsi(m)) changes of spermatozoa using
      potentiometric dyes may be a reliable test to determine sperm quality. However,
      the use of the potentiometric dyes in sperm samples has not been compared.
      METHODS: We have studied sperm samples from 28 infertile patients enrolled in an
      IVF programme in flow cytometry after staining of spermatozoa with four commonly
      used potentiometric dyes. Sperm motility was evaluated visually. RESULTS: As
      expected, JC-1 seems to detect specifically Deltapsi(m) changes, CMX-Ros,
      DiOC(6)(3) and TMRE fluorescence is easily analysed and the latter three
      fluorochromes are particularly suitable for multiparametric staining.
      Irrespective of the Deltapsi(m)-dependent fluorochromes used to stain
      spermatozoa, a positive correlation was found between the percentage of
      Deltapsi(m)(high) cells and forward motility and also with high fertilization
      rates after IVF. CONCLUSION: The four fluorochromes may be useful for evaluation
      of sperm samples from infertile patients. The choice of the potentiometric dyes
      will depend on their fluorescence characteristics in order to use them in
      combination with other fluorescent markers.

PMID- 15256506
TI  - Early ovarian ageing: are women with polycystic ovaries protected?
AB  - Screening asymptomatic women in the general population for 'early ovarian ageing'
      will be more effective in high-risk groups. Recent findings support the
      hypothesis that women with polycystic ovaries (PCO) may have actually been born
      with a larger pool of resting follicles. The mechanism is almost certainly
      genetic and occurs in fetal life. If, as is widely accepted, the rate of
      depletion of the ovarian reserve depends primarily on the size of the remaining
      pool of small follicles, women with PCO will be unlikely to undergo an
      accelerated depletion of their follicle pool, normally seen in the late thirties,
      significantly earlier. In terms of asymptomatic screening for early ovarian
      ageing in the general population, women with PCO constitute a low-risk group and
      should therefore be excluded.

PMID- 15256507
TI  - Incongruent patterns of local and global genome size evolution in cotton.
AB  - Genome sizes in plants vary over several orders of magnitude, reflecting a
      combination of differentially acting local and global forces such as biases in
      indel accumulation and transposable element proliferation or removal. To gain
      insight into the relative role of these and other forces, approximately 105 kb of
      contiguous sequence surrounding the cellulose synthase gene CesA1 was compared
      for the two coresident genomes (AT and DT) of the allopolyploid cotton species,
      Gossypium hirsutum. These two genomes differ approximately twofold in size,
      having diverged from a common ancestor approximately 5-10 million years ago (Mya)
      and been reunited in the same nucleus at the time of polyploid formation,
      approximately 1-2 Mya. Gene content, order, and spacing are largely conserved
      between the two genomes, although a few transposable elements and a single cpDNA
      fragment distinguish the two homoeologs. Sequence conservation is high in both
      intergenic and genic regions, with 14 conserved genes detected in both genomes
      yielding a density of 1 gene every 7.5 kb. In contrast to the twofold overall
      difference in DNA content, no disparity in size was observed for this 105-kb
      region, and 555 indels were detected that distinguish the two homoeologous BACs,
      approximately equally distributed between AT and DT in number and aggregate size.
      The data demonstrate that genome size evolution at this phylogenetic scale is not
      primarily caused by mechanisms that operate uniformly across different genomic
      regions and components; instead, the twofold overall difference in DNA content
      must reflect locally operating forces between gene islands or in largely gene
      free regions.

PMID- 15256508
TI  - cis-Regulatory and protein evolution in orthologous and duplicate genes.
AB  - The relationship between protein and regulatory sequence evolution is a central
      question in molecular evolution. It is currently not known to what extent changes
      in gene expression are coupled with the evolution of protein coding sequences, or
      whether these changes differ among orthologs (species homologs) and paralogs
      (duplicate genes). Here, we develop a method to measure the extent of
      functionally relevant cis-regulatory sequence change in homologous genes, and
      validate it using microarray data and experimentally verified regulatory elements
      in different eukaryotic species. By comparing the genomes of Caenorhabditis
      elegans and C. briggsae, we found that protein and regulatory evolution is weakly
      coupled in orthologs but not paralogs, suggesting that selective pressure on gene
      expression and protein evolution is quite similar and persists for a significant
      amount of time following speciation but not gene duplication. Additionally,
      duplicates of both species exhibit a dramatic acceleration of both regulatory and
      protein evolution compared to orthologs, suggesting increased directional
      selection and/or relaxed selection on both gene expression patterns and protein
      function in duplicate genes.

PMID- 15256509
TI  - Comparative evolutionary genomics of androgen-binding protein genes.
AB  - Allelic variation within the mouse androgen-binding protein (ABP) alpha subunit
      gene (Abpa) has been suggested to promote assortative mating and thus prezygotic
      isolation. This is consistent with the elevated evolutionary rates observed for
      the Abpa gene, and the Abpb and Abpg genes whose products (ABPbeta and ABPgamma)
      form heterodimers with ABPalpha. We have investigated the mouse sequence that
      contains the three Abpa/b/g genes, and orthologous regions in rat, human, and
      chimpanzee genomes. Our studies reveal extensive "remodeling" of this region:
      Duplication rates of Abpa-like and Abpbg-like genes in mouse are >2 orders of
      magnitude higher than the average rate for all mouse genes; synonymous nucleotide
      substitution rates are twofold higher; and the Abpabg genomic region has expanded
      nearly threefold since divergence of the rodents. During this time, one in six
      amino acid sites in ABPbetagamma-like proteins appear to have been subject to
      positive selection; these may constitute a site of interaction with receptors or
      ligands. Greater adaptive variation among Abpbg-like sequences than among Abpa
      like sequences suggests that assortative mating preferences are more influenced
      by variation in Abpbg-like genes. We propose a role for ABPalpha/beta/gamma
      proteins as pheromones, or in modulating odorant detection. This would account
      for the extraordinary adaptive evolution of these genes, and surrounding genomic
      regions, in murid rodents.

PMID- 15256510
TI  - The repetitive landscape of the chicken genome.
AB  - Cot-based cloning and sequencing (CBCS) is a powerful tool for isolating and
      characterizing the various repetitive components of any genome, combining the
      established principles of DNA reassociation kinetics with high-throughput
      sequencing. CBCS was used to generate sequence libraries representing the high,
      middle, and low-copy fractions of the chicken genome. Sequencing high-copy DNA of
      chicken to about 2.7 x coverage of its estimated sequence complexity led to the
      initial identification of several new repeat families, which were then used for a
      survey of the newly released first draft of the complete chicken genome. The
      analysis provided insight into the diversity and biology of known repeat
      structures such as CR1 and CNM, for which only limited sequence data had
      previously been available. Cot sequence data also resulted in the identification
      of four novel repeats (Birddawg, Hitchcock, Kronos, and Soprano), two new
      subfamilies of CR1 repeats, and many elements absent from the chicken genome
      assembly. Multiple autonomous elements were found for a novel Mariner-like
      transposon, Galluhop, in addition to nonautonomous deletion derivatives.
      Phylogenetic analysis of the high-copy repeats CR1, Galluhop, and Birddawg
      provided insight into two distinct genome dispersion strategies. This study also
      exemplifies the power of the CBCS method to create representative databases for
      the repetitive fractions of genomes for which only limited sequence data is
      available.

PMID- 15256512
TI  - Segmental duplications flank the multiple sclerosis locus on chromosome 17q.
AB  - Large chromosomal rearrangements, duplications, and inversions are relatively
      common in mammalian genomes. Here we report interesting features of DNA strands
      flanking a Multiple Sclerosis (MS) susceptibility locus on Chromosome 17q24.
      During the positional cloning process of this 3-Mb locus, several markers showed
      a radiation hybrid clone retention rate above the average (1.8-fold), suggestive
      for the existence of duplicated sequences in this region. FISH studies
      demonstrated multiple signals with three of the tested regional BACs, and 24 BACs
      out of 187 showed evidence for duplication in shotgun sequence comparisons of the
      17q22-q24 region. Specifically, the MS haplotype region proved to be flanked by
      palindromic sequence stretches and by long segmental intrachromosomal
      duplications in which highly homologous DNA sequences (>96% identity) are present
      at both ends of the haplotype. Moreover, the 3-Mb DNA segment, flanked by the
      duplications, is inverted in the mouse genome when compared with the orientation
      in human and chimp. The segmental duplication architecture surrounding the MS
      locus raises the possibility that a nonallelic homologous recombination between
      duplications could affect the biological activity of the regional genes, perhaps
      even contributing to the genetic background of MS.

PMID- 15256511
TI  - The binding sites for the chromatin insulator protein CTCF map to DNA methylation
      free domains genome-wide.
AB  - All known vertebrate chromatin insulators interact with the highly conserved,
      multivalent 11-zinc finger nuclear factor CTCF to demarcate expression domains by
      blocking enhancer or silencer signals in a position-dependent manner. Recent
      observations document that the properties of CTCF include reading and propagating
      the epigenetic state of the differentially methylated H19 imprinting control
      region. To assess whether these findings may reflect a universal role for CTCF
      targets, we identified more than 200 new CTCF target sites by generating DNA
      microarrays of clones derived from chromatin-immunopurified (ChIP) DNA followed
      by ChIP-on-chip hybridization analysis. Target sites include not only known loci
      involved in multiple cellular functions, such as metabolism, neurogenesis,
      growth, apoptosis, and signalling, but potentially also heterochromatic
      sequences. Using a novel insulator trapping assay, we also show that the majority
      of these targets manifest insulator functions with a continuous distribution of
      stringency. As these targets are generally DNA methylation-free as determined by
      antibodies against 5-methylcytidine and a methyl-binding protein (MBD2), a CTCF
      based network correlates with genome-wide epigenetic states.

PMID- 15256513
TI  - Comparative genomics of transcriptional control in the human malaria parasite
      Plasmodium falciparum.
AB  - The life cycle of the parasite Plasmodium falciparum, responsible for the most
      deadly form of human malaria, requires specialized protein expression for
      survival in the mammalian host and insect vector. To identify components of
      processes controlling gene expression during its life cycle, the malarial genome-
      along with seven crown eukaryote group genomes--was queried with a reference set
      of transcription-associated proteins (TAPs). Following clustering on the basis of
      sequence similarity of the TAPs with their homologs, and together with hidden
      Markov model profile searches, 156 P. falciparum TAPs were identified. This
      represents about a third of the number of TAPs usually found in the genome of a
      free-living eukaryote. Furthermore, the P. falciparum genome appears to contain a
      low number of sequences, which are highly conserved and abundant within the
      kingdoms of free-living eukaryotes, that contribute to gene-specific
      transcriptional regulation. However, in comparison with these other eukaryotic
      genomes, the CCCH-type zinc finger (common in proteins modulating mRNA decay and
      translation rates) was found to be the most abundant in the P. falciparum genome.
      This observation, together with the paucity of malarial transcriptional
      regulators identified, suggests Plasmodium protein levels are primarily
      determined by posttranscriptional mechanisms.

PMID- 15256514
TI  - Haplotype and missing data inference in nuclear families.
AB  - Determining linkage phase from population samples with statistical methods is
      accurate only within regions of high linkage disequilibrium (LD). Yet, affected
      individuals in a genetic mapping study, including those involving cases and
      controls, may share sequences identical-by-descent stretching on the order of 10s
      to 100s of kilobases, quite possibly over regions of low LD in the population. At
      the same time, inferring phase from nuclear families may be hampered by missing
      family members, missing genotypes, and the noninformativity of certain genotype
      patterns. In this study, we reformulate our previous haplotype reconstruction
      algorithm, and its associated computer program, to phase parents with information
      derived from population samples as well as from their offspring. In applications
      of our algorithm to 100-kb stretches, simulated in accordance to a Wright-Fisher
      model with typical levels of LD in humans, we find that phase reconstruction for
      160 trios with 10% missing data is highly accurate (>90%) over the entire length.
      Furthermore, our algorithm can estimate allelic status for missing data at high
      accuracy (>95%). Finally, the input capacity of the program is vast, easily
      handling thousands of segregating sites in > or = 1000 chromosomes.

PMID- 15256515
TI  - Clustering of DNA sequences in human promoters.
AB  - We have determined the distribution of each of the 65,536 DNA sequences that are
      eight bases long (8-mer) in a set of 13,010 human genomic promoter sequences
      aligned relative to the putative transcription start site (TSS). A limited number
      of 8-mers have peaks in their distribution (cluster), and most cluster within 100
      bp of the TSS. The 156 DNA sequences exhibiting the greatest statistically
      significant clustering near the TSS can be placed into nine groups of related
      sequences. Each group is defined by a consensus sequence, and seven of these
      consensus sequences are known binding sites for the transcription factors (TFs)
      SP1, NF-Y, ETS, CREB, TBP, USF, and NRF-1. One sequence, which we named Clus1, is
      not a known TF binding site. The ninth sequence group is composed of the strand
      specific Kozak sequence that clusters downstream of the TSS. An examination of
      the co-occurrence of these TF consensus sequences indicates a positive
      correlation for most of them except for sequences bound by TBP (the TATA box).
      Human mRNA expression data from 29 tissues indicate that the ETS, NRF-1, and
      Clus1 sequences that cluster are predominantly found in the promoters of
      housekeeping genes (e.g., ribosomal genes). In contrast, TATA is more abundant in
      the promoters of tissue-specific genes. This analysis identified eight DNA
      sequences in 5082 promoters that we suggest are important for regulating gene
      expression.

PMID- 15256516
TI  - Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls:
      discrepancies between genotype, blood lipid concentrations, and coronary disease
      risk.
AB  - BACKGROUND: Blood lipid concentrations are causally related to the risk of
      coronary heart disease (CHD). Various associations between CHD risk and genes
      that moderately affect plasma lipid levels have been described, but previous
      studies have typically involved too few 'cases' to assess these associations
      reliably. METHODS: The present study involves 4685 cases of myocardial infarction
      (MI) and 3460 unrelated controls without diagnosed cardiovascular disease. Six
      polymorphisms of four 'lipid-related' genes were genotyped. RESULTS: For the
      apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphism, the average increase in
      the plasma ratio of apolipoprotein B to apolipoprotein A(1) (apoB/apoA(1) ratio)
      among controls was 0.082 (s.e. 0.007) per stepwise change from epsilon3/epsilon2
      to epsilon3/epsilon3 to epsilon3/epsilon4 genotype (trend P < 0.0001). The case
      control comparison yielded a risk ratio for MI of 1.16 (95% CI: 1.06, 1.27; P =
      0.001) per stepwise change in these genotypes. But, this risk ratio was not as
      extreme as would have been expected from the corresponding differences in plasma
      apoB/apoA(1) ratio between genotypes. Hence, following adjustment for the
      measured level of the plasma apoB/apoA(1) ratio, the direction of the risk ratio
      per stepwise change reversed to 0.83 (95% CI: 0.74, 0.92; P < 0.001). Similarly,
      for the apolipoprotein B Asn4311Ser and Thr71Ile polymorphisms, genotypes
      associated with more adverse plasma apolipoprotein concentrations were associated
      with significantly lower risk of MI after adjustment for the apoB/apoA(1) ratio.
      The B2 allele of the cholesteryl ester transfer protein TaqIb polymorphism was
      associated with a significantly lower plasma apoB/apoA(1) ratio, but with no
      significant difference in the risk of MI. Finally, the lipoprotein lipase
      Asn291Ser and T4509C (PvuII) polymorphisms did not produce clear effects on
      either the plasma apoB/apoA(1) ratio or the risk of MI. CONCLUSIONS: It remains
      unresolved why some of these genetic factors that produce lifelong effects on
      plasma lipid concentrations have significantly less than the correspondingly
      expected effects on CHD rates in adult life.

PMID- 15256517
TI  - Commentary: The message is rarely simple: the J-curve and beyond.

PMID- 15256518
TI  - The association of maternal growth and socio-economic measures with infant
      birthweight in four ethnic groups.
AB  - BACKGROUND: Both maternal socio-economic status (SES) and growth measures are
      themselves interrelated and are also related to infant birthweight. The objective
      of this study is to compare the relative importance of such maternal measures as
      determinants of birthweight of female infants-the prospective mothers of the next
      generation. METHODS: The study base was derived from a population-based
      multiethnic intergenerational cohort: the Washington State Intergenerational
      Cohort. Infants of mothers from four ethnic groups were included: non-Hispanic
      Whites, African Americans, Native Americans, and Hispanics. We generated simple,
      partial, and multiple correlation coefficients to investigate the association
      between birthweight and the maternal growth and SES measures. RESULTS: While
      there were slight differences among the ethnic groups, generally each of three
      maternal pre-conceptional growth measures-birthweight, stature, and pre-pregnant
      weight-was a stronger predictor of female infant birthweight than were each of
      the five maternal SES factors-age, parity, marital status, educational
      attainment, and prenatal care onset. After accounting for the proportion of
      variation in birthweight explained by the maternal growth measures and maternal
      smoking, the addition of the five SES variables added relatively little to the
      prediction of infant birthweight. The maximal multiple correlation coefficients
      (R2) yield values ranging from 9.5% to 12.8%. CONCLUSIONS: A mother's growth
      before pregnancy is a stronger predictor of infant birthweight than is her
      current socio-economic circumstance. Since the mother's growth must have been
      influenced by the socio-economic circumstances of her family of upbringing, this
      further highlights the intergenerational contribution on a woman's reproductive
      success.

PMID- 15256519
TI  - The association of grandmaternal and maternal factors with maternal adult
      stature.
AB  - BACKGROUND: Stature is an important determinant of several reproductive and non
      reproductive health problems. Documentation of secular trends in stature has been
      based primarily on cross-sectional studies of special populations, primarily of
      men. The objective of this study is to determine how growth and socio-economic
      status (SES) factors relate to stature changes among lineal female relatives,
      maternal grandmothers to mothers. METHODS: The study base was derived from a
      population-based intergenerational cohort which linked several statewide
      databases to data from the mothers' own birth certificates: the Washington State
      Intergenerational Cohort. Mothers in these ethnic groups were separately studied:
      non-Hispanic Whites, African Americans, Native Americans, Hispanics. We generated
      simple, partial, and multiple correlation coefficients to investigate the
      association between stature and other growth and SES factors. RESULTS: A mother's
      stature is determined partly by her own mother's stature and partly by her
      birthweight. These two measures are individually stronger predictors of stature
      than are several available SES factors considered in combination-grandmother's
      age, parity, marital status, and mother's age. The maximal multiple correlation
      models yielded R2 values from 18% to 28%. CONCLUSIONS: Growth measures are
      stronger predictors of intergenerational changes in stature than are the several
      available socio-economic factors. However, socio-economic factors are partly
      responsible for the level of achieved prenatal and postnatal growth. Since
      grandmother's stature is a determinant of mother's birthweight, which in turn is
      a determinant of infant birthweight, some environmentally influenced determinants
      of some birth outcomes are already established before a prospective mother is
      conceived or born.

PMID- 15256520
TI  - Population survey to determine risk factors for Mycobacterium leprae transmission
      and infection.
AB  - BACKGROUND: Not every leprosy patient is equally effective in transmitting
      Mycobacterium leprae. We studied the spatial distribution of infection (using
      seropositivity as a marker) in the population to identify which disease
      characteristics of leprosy patients are important in transmission. METHODS:
      Clinical data and blood samples for anti-M. leprae ELISA were collected during a
      cross-sectional survey on five Indonesian islands highly endemic for leprosy. A
      geographic information system (GIS) was used to define contacts of patients. We
      investigated spatial clustering of patients and seropositive people and used
      logistic regression to determine risk factors for seropositivity. RESULTS: Of the
      3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between
      islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five
      clusters of patients and two clusters of seropositives were detected. In
      multivariate analysis, seropositivity significantly differed by leprosy status,
      age, sex, and island. Serological status of patients appeared to be the best
      discriminator of contact groups with higher seroprevalence: contacts of
      seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI 0.922
      3.31). This increased seroprevalence was strongest for contact groups living < or
      =75 m of two seropositive patients (aOR = 3.07; 95% CI 1.74-5.42). CONCLUSIONS:
      In this highly endemic area for leprosy, not only household contacts of
      seropositive patients, but also people living in the vicinity of a seropositive
      patient were more likely to harbour antibodies against M. leprae. Through
      measuring the serological status of patients and using a broader definition of
      contacts, higher risk groups can be more specifically identified.

PMID- 15256521
TI  - Insulin and IGF-I as determinants of low "Western" cancer rates in the rural
      third world.

PMID- 15256522
TI  - Impact of El Nino and malaria on birthweight in two areas of Tanzania with
      different malaria transmission patterns.
AB  - BACKGROUND: Malaria infection increases low birthweight especially in
      primigravidae. Malaria epidemics occur when weather conditions favour this vector
      borne disease. Forecasting using the El Nino Southern Oscillation (ENSO) may
      assist in anticipating epidemics and reducing the impact of a disease which is an
      important cause of low birthweight. The aim of the present study was to determine
      the impact of the malaria epidemic in East Africa during 1997-1998 on
      birthweights in two different areas of Tanzania and to explore ESNO's potential
      for forecasting low birthweight risk in pregnant women. METHOD: A retrospective
      analysis of birthweight differences between primigravidae and multigravidae in
      relation to malaria cases and rainfall for two different areas of Tanzania:
      Kagera, which experiences severe outbreaks of malaria, and Morogoro which is
      holoendemic. Birthweight and parity data and malaria admissions were collected
      over a 10-year period from two district hospitals in these locations. RESULTS:
      The risk of delivering a low birthweight baby in the first pregnancy increases
      approximately 5 months following a malaria epidemic. An epidemic of marked
      reduced birthweight in primigravidae compared with multigravidae occurred,
      related to the ENSO of 1997-1998. In Kagera this birthweight difference and the
      risk of low birthweight were significantly lower compared with Morogoro, except
      after the ENSO when the two areas had similar differences. No significant
      interaction was noted between secundigravidae and any of the risk periods. The
      results indicate that the pressure of malaria is much greater on pregnant women,
      especially primigravidae, living in the Morogoro location. CONCLUSIONS:
      Surveillance of birthweight differences between primigravidae and multigravidae
      is a useful indicator of malaria exposure.

PMID- 15256523
TI  - Predictors of the quality of health worker treatment practices for uncomplicated
      malaria at government health facilities in Kenya.
AB  - BACKGROUND: When replacing failing drugs for malaria with more effective drugs,
      an important step towards reducing the malaria burden is that health workers (HW)
      prescribe drugs according to evidence-based guidelines. Past studies have shown
      that HW commonly do not follow guidelines, yet few studies have explored with
      appropriate methods why such practices occur. METHODS: We analysed data from a
      survey of government health facilities in four Kenyan districts in which HW
      consultations were observed, caretakers and HW were interviewed, and health
      facility assessments were performed. The analysis was limited to children 2-59
      months old with uncomplicated malaria. Treatment was defined as recommended
      (antimalarial recommended by national guidelines), a minor error (effective, but
      non-recommended antimalarial), or inappropriate (no effective antimalarial).
      RESULTS: We evaluated 1006 consultations performed by 135 HW at 81 facilities:
      567 children received recommended treatment, 314 had minor errors, and 125
      received inappropriate treatment (weighted percentages: 56.9%, 30.4%, and 12.7%).
      Multivariate logistic regression analysis revealed that programmatic
      interventions such as in-service malaria training, provision of guidelines and
      wall charts, and more frequent supervision were significantly associated with
      better treatment quality. However, neither in-service training nor possession of
      the guideline document showed an effect by itself. More qualified HW made more
      errors: both major and minor errors (but generally more minor errors) when second
      line drugs were in stock, and more major errors when second-line drugs were not
      in stock. Child factors such as age and a main complaint of fever were also
      associated with treatment quality. CONCLUSIONS: Our results support the use of
      several programmatic strategies that can redress HW deficiencies in malaria
      treatment. Targeted cost-effectiveness trials would help refine these strategies
      and provide more precise guidance on affordable and effective ways to strengthen
      and maintain HW practices.

PMID- 15256524
TI  - Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1,
      NAT2, PON1, PON2 and MTHFR.
AB  - BACKGROUND: Impaired metabolism of toxic chemicals is a postulated mechanism
      underlying multiple chemical sensitivity (MCS). Because genetic variation alters
      the rate of chemical metabolism, this study was designed to determine if MCS
      cases differed from controls for genetic polymorphisms in drug-metabolizing
      enzymes. METHODS: Female Caucasian participants (203 cases and 162 controls) were
      drawn from a larger case-control study based on a reproducible and validated case
      definition. Common polymorphisms for CYP2D6, NAT1, NAT2, PON1, and PON2 were
      genotyped. RESULTS: Comparing cases and controls, significant differences were
      found in genotype distributions for CYP2D6 (P = 0.02) and NAT2 (P = 0.03).
      Compared with the referent homozygous inactive (CYP2D6) or slow (NAT2)
      metabolizers, the odds for being CYP2D6 homozygous active (OR = 3.36, P = 0.01)
      and NAT2 rapid (OR = 4.14, P = 0.01) were significantly higher in cases than
      controls. The odds for being heterozygous for PON1-55 (OR = 2.05, P = 0.04) and
      PON1-192 (OR = 1.57, P = 0.04) were also significantly higher in cases.
      CONCLUSIONS: A genetic predisposition for MCS may involve altered
      biotransformation of environmental chemicals. The CYP2D6 enzyme activates and
      inactivates toxins; the NAT2 enzyme bioactivates arylamines to protein-binding
      metabolites. A gene-gene interaction between CYP2D6 and NAT2 suggested that rapid
      metabolism for both enzymes may confer substantially elevated risk (OR = 18.7, P
      = 0.002). Our finding parallels others' observation of a link between PON1
      heterozygosity and neurological symptoms in Gulf War syndrome. This first
      demonstration of genetic variation in drug-metabolizing enzymes in association
      with MCS requires replication. However, it suggests new research directions on
      genetically variable toxin pathways that might be important in MCS.

PMID- 15256525
TI  - Multiple parasite infections and their relationship to self-reported morbidity in
      a community of rural Cote d'Ivoire.
AB  - BACKGROUND: Concomitant parasitic infections are common in the developing world,
      yet most studies focus on a single parasite in a narrow age group. We
      investigated the extent of polyparasitism and parasite associations, and related
      these findings to self-reported morbidity. METHODS: Inhabitants of 75 randomly
      selected households from a single village in western Cote d'Ivoire provided
      multiple faecal specimens and a single finger prick blood sample. The Kato-Katz
      technique and a formol-ether concentration method were employed to screen faecal
      samples for Schistosoma mansoni, soil-transmitted helminths and intestinal
      protozoa. Giemsa-stained blood smears were analysed for malaria parasites. A
      questionnaire was administered for collection of demographic information and self
      reported morbidity indicators. RESULTS: Complete parasitological data were
      obtained for 500/561 (89.1%) participants, similarly distributed among sex, with
      an age range from 5 days to 91 years. The prevalences of Plasmodium falciparum,
      hookworms, Entamoeba histolytica/E. dispar, and S. mansoni were 76.4%, 45.0%,
      42.2%, and 39.8%, respectively. Three-quarters of the population harboured three
      or more parasites concurrently. Multivariate analysis revealed significant
      associations between several pairs of parasites. Some parasitic infections and
      the total number of parasites were significantly associated with self-reported
      morbidity indicators. CONCLUSIONS: Our data confirm that polyparasitism is very
      common in rural Cote d'Ivoire and that people have clear perceptions about the
      morbidity caused by some of these parasitic infections. Our findings can be used
      for the design and implementation of sound intervention strategies to mitigate
      morbidity and co-morbidity.

PMID- 15256526
TI  - When the population approach to prevention puts the health of individuals at
      risk.
AB  - The population approach to prevention has been described as one of the "absolute
      truths" of preventive medicine. However, when the relationship between risk
      factor exposure levels and associated risk is J-shaped the population approach
      can increase risk in a small number of individuals. There is evidence that the
      relationship between a variety of exposures and all-cause morbidity and mortality
      is J-shaped. However, such relationships are often overlooked by epidemiological
      investigations which focus on cause-specific morbidity and mortality. Although
      the overall beneficial effect of population interventions may outweigh any
      negative effect seen, the effect on the individuals concerned should not be
      overlooked--especially when they can be easily identifiable before the
      intervention. Procedures, akin to gaining informed consent in clinical
      situations, may be required to ensure that individuals who are at high risk of
      being negatively affected by population interventions understand the risks
      involved and have the opportunity to opt out.

PMID- 15256527
TI  - Socioeconomic trajectories across the life course and health outcomes in midlife:
      evidence for the accumulation hypothesis?
AB  - BACKGROUND: Recent research in social epidemiology has established the importance
      of considering the accumulation of advantage and disadvantage across the life
      course when examining adult health outcomes. This paper examines (1) accumulation
      across trichotomous categories of socioeconomic position (SEP), and (2)
      accumulation in analysis stratified by adult SEP. METHODS: Data are from the
      Whitehall II study. Each participant was categorized as having high (0),
      intermediate (1), or low (2) SEP at three time points in the life course, leading
      to 27 socioeconomic trajectories. These trajectories were summarized to yield a
      scale ranging from 0 (high SEP at all three time points) to 6 (low SEP at all
      three time points). Logistic regression was used to examine odds of incident
      coronary heart disease (CHD), poor mental and physical functioning, and minor
      psychiatric disorder. RESULTS: There was a graded linear relationship between
      accumulation of socioeconomic exposure and health. Men with a score of 6 had
      increased odds of CHD (2.53, 95% CI: 1.3, 5.1), poor physical functioning (2.19,
      95% CI: 1.4, 4.1), and poor mental functioning (2.60, 95% CI: 1.4, 4.9) compared
      with men with a score of 0. In women there was an accumulation effect for CHD and
      physical functioning. No cumulative effect of SEP on minor psychiatric disorder
      was observed. The effects of accumulation were weaker in analyses stratified by
      adult SEP, with early deprivation followed by high adult SEP particularly
      detrimental for CHD. CONCLUSIONS: The health effects of socioeconomic
      disadvantage accumulate over the life course. In addition to accumulation
      effects, analysis stratified by adult SEP also provided support for the critical
      period and the pathway model.

PMID- 15256528
TI  - Are social comparisons of homes and cars related to psychosocial health?
AB  - BACKGROUND: It has been suggested that perceiving oneself to be inferior to those
      around one is a psychosocial risk factor associated with ill health. The aim of
      this study was to examine whether negative social comparisons of the worth of two
      common assets (homes and cars) were related to psychosocial health (i.e. lower
      self-esteem and mastery, higher anxiety, and depression). METHODS: A postal
      questionnaire was sent to a random sample of adults in the West of Scotland
      (sampling from the 1997 electoral roll, response rate was 50%, achieved sample
      2838). RESULTS: Having adjusted for socio-demographic variables, rating one's
      house/flat as worth less than others was associated with lower self-esteem (P <
      0.001) and mastery (P < 0.001) and higher depression (P < 0.007) and anxiety (P <
      0.012). Rating one's car as worth less than others was not significantly
      associated with these psychosocial variables. CONCLUSIONS: Our findings lend some
      support, but only in relation to the home, to the hypothesis that perceiving
      oneself to be worse off in relation to those around is related to poorer
      psychosocial health.

PMID- 15256529
TI  - Commentary: Catch-up growth in humans--a comment on poverty, birthweight, and
      infant weight gain in Hertfordshire.

PMID- 15256531
TI  - European Congress of Epidemiology, 8-11 September 2004, Porto, Portugal.
      Abstracts.

PMID- 15256530
TI  - Poverty, birthweight, and infant weight gain in Hertfordshire, 1923-1939.
AB  - OBJECTIVE: To investigate the association between poverty, birthweight, and
      infant weight gain in Hertfordshire, 1923-1939. DESIGN: Cohort study based on the
      Hertfordshire Health Visitors' Register (HHVR). SETTING: The population of
      Hertfordshire, and a sub-sample of five Hertfordshire towns-Hoddesdon,
      Berkhampstead, Hertford, Hitchin, and Bishops Stortford-extracted from the HHVR.
      SUBJECTS: Some 71 201 live birth entries in the HHVR and a sample of 13,649 live
      birth entries for the five towns. MEASURE OF POVERTY: Rateable value of birth
      addresses reflecting market and rental value of housing. MAIN OUTCOME MEASURES:
      Birthweight, and infant weight gain (z score of weight at one year minus z score
      of birthweight). RESULTS: In Hertfordshire as a whole there was a reduction in
      mean birthweight from 7.7 pounds (lbs) in 1923 to 7.4 lbs in 1939. Over the same
      time period there was an increase in mean infant weight gain, although with a
      degree of variation within the trend. In the sample of five towns there was no
      association between rateable value and birthweight, but a significant association
      between rateable value and both weight at one year, and weight gain during the
      first year of life. CONCLUSION: In Hertfordshire average birthweight declined,
      whereas weight gain during the first year of life tended to increase, at a time
      when, nationally, calorific intake and per capita consumption of a range of
      nutritional ingredients was rising. Poverty, as measured by rateable value, did
      not correlate with birthweight but was associated with weight gain during the
      first year of life. These findings suggest that nutritional poverty had a more
      significant influence on post-natal weight gain than it did on birthweight.

PMID- 15256532
TI  - Adrenocortical tumorigenesis in transgenic mice expressing the inhibin alpha
      subunit promoter/simian virus 40 T-antigen transgene: relationship between
      ectopic expression of luteinizing hormone receptor and transcription factor GATA
      4.
AB  - We have analyzed the ontogeny and putative mechanisms of transregulation of LH
      receptor (LHR) and transcription factor GATA-4, coexpressed during the
      adrenocortical tumorigenesis of prepubertally gonadectomized transgenic (TG) mice
      expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen
      (inhalpha/Tag) transgene. The onset of adrenal LHR mRNA and protein expression
      coincided with that of GATA-4 at the age of 4 months and preceded the appearance
      of discernible adrenal tumors at about 6 months. In situ hybridization and double
      immunohistochemistry demonstrated colocalization of the LHR and GATA-4 messages
      and proteins in the adrenal cortex. A GATA-4 expression plasmid cotransfected
      with a murine LHR promoter-driven luciferase reporter plasmid, containing a
      consensus GATA-binding site, induced a dose-dependent significant transactivation
      of the LHR promoter in nonsteroidogenic human embryonic kidney 293, steroidogenic
      murine mLTC-1 Leydig cells and in murine adrenal Y-1 cells. The Calpha1 cells
      derived from an Inhalpha/Tag adrenal tumor did not show this response, apparently
      due to their high endogenous GATA-4 expression. However, an additional link
      between GATA-4 and LHR in Calpha1 cells was provided upon the LH/human chorionic
      gonadotropin stimulation of LHR promoter activity; mutations or deletion of the
      consensus GATA-4 binding site of the LHR promoter abolished this transactivation.
      EMSAs further proved GATA-4 binding to the putative consensus GATA recognition
      site. Our results demonstrate direct interrelationship between LHR and GATA-4
      expression during adrenocortical tumorigenesis of the inhalpha/Tag mice. There is
      apparently a positive and reciprocal feed-forward amplification link between LHR
      and GATA-4 expression. This mechanism gradually and in synergy with Tag
      expression leads to formation of the LH-dependent adrenocortical tumors.

PMID- 15256533
TI  - Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and
      progesterone receptor.
AB  - ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs) is
      a multifunctional protease that is expressed in periovulatory follicles. Herein
      we show that induction of ADAMTS-1 message in vivo and transcription of the
      ADAMTS-1 promoter in cultured granulosa cells are dependent on separable but
      coordinate actions of LH and the progesterone receptor (PR). To analyze the
      molecular mechanisms by which LH and PR regulate this gene, truncations and site
      specific mutants of ADAMTS-1 promoter-luciferase reporter constructs (ADAMTS-1
      Luc) were generated and transfected into rat granulosa cell cultures. Three
      regions of the promoter were found to be important for basal activity, two of
      which were guanine cytosine-rich binding sites for specificity proteins Sp1/Sp3
      and the third bound a nuclear factor 1-like factor. Despite the absence of a
      consensus PR DNA response element in the proximal ADAMTS-1 promoter,
      cotransfection of a PRA (or PRB) expression vector stimulated ADAMTS-1 promoter
      activity, a response that was reduced by the PR antagonist ZK98299. Forskolin
      plus phorbol myristate acetate also increased promoter activity and, when added
      to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further.
      Activation of the ADAMTS-1 promoter by PRA involves functional CAAT enhancer
      binding protein beta, nuclear factor 1-like factor, and three Sp1/Sp3 binding
      sites as demonstrated by transfection of mutated promoter constructs. In summary,
      LH and PRA/B exert distinct but coordinate effects on transactivation of the
      ADAMTS-1 gene in granulosa cells in vivo and in vitro with PR acting as an
      inducible coregulator of the ADAMTS-1 gene.

PMID- 15256534
TI  - Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates
      with ligand-stimulated growth of prostate cancer cells.
AB  - Prostate cancers respond to treatments that suppress androgen receptor (AR)
      function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR
      antagonists in clinical use. As CPA has substantial agonist activity, it was
      examined to identify AR coactivator/corepressor interactions that may mediate
      androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated
      by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal
      interactions or recruit beta-catenin, indicating a nonagonist conformation.
      Nonetheless, CPA did not enhance AR interaction with nuclear receptor
      corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated
      AR-nuclear receptor corepressor binding. The role of coactivators was further
      assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which
      converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist
      that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were
      coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by beta
      catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A
      AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and
      not beta-catenin. In contrast, beta-catenin coactivated a bicalutamide-responsive
      mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further
      implicating beta-catenin recruitment in AR-stimulated growth. Androgen-stimulated
      prostate-specific antigen gene expression in LNCaP cells could be modulated by
      beta-catenin, and endogenous c-myc expression was repressed by
      dihydrotestosterone, but not CPA. These results indicate that interactions
      between AR and beta-catenin contribute to prostate cell growth in vivo, although
      specific growth promoting genes positively regulated by AR recruitment of beta
      catenin remain to be identified.

PMID- 15256535
TI  - Tissue-specific differences in activation of atypical protein kinase C and
      protein kinase B in muscle, liver, and adipocytes of insulin receptor substrate-1
      knockout mice.
AB  - Insulin receptor substrates (IRSs) 1 and 2 are postulated to control the
      activation of phosphatidylinositol 3-kinase (PI3K)-dependent signaling factors,
      namely, atypical protein kinase C (aPKC) and protein kinase B (PKB)/Akt, which
      mediate metabolic effects of insulin. However, it is uncertain whether aPKC and
      PKB are activated together or differentially in response to IRS-1 and IRS-2
      activation in insulin-sensitive tissues. Presently, we examined insulin
      activation of aPKC and PKB in vastus lateralis muscle, adipocytes, and liver in
      wild-type and IRS-1 knockout mice, and observed striking tissue-specific
      differences. In muscle of IRS-1 knockout mice, the activation of both aPKC and
      PKB was markedly diminished. In marked contrast, only aPKC activation was
      diminished in adipocytes, and only PKB activation was diminished in liver. These
      results suggest that IRS-1 is required for: 1) activation of both aPKC and PKB in
      muscle; 2) aPKC, but not PKB, activation in adipocytes; and 3) PKB, but not aPKC,
      activation in liver. Presumably, IRS-2 or other PI3K activators account for the
      normal activation of aPKC in liver and PKB in adipocytes of IRS-1 knockout mice.
      These complexities in aPKC and PKB activation may be relevant to metabolic
      abnormalities seen in tissues in which IRS-1 or IRS-2 is specifically or
      predominantly down-regulated.

PMID- 15256536
TI  - High mobility group B proteins facilitate strong estrogen receptor binding to
      classical and half-site estrogen response elements and relax binding selectivity.
AB  - The estrogen receptor alpha (ER) is a ligand-dependent transcription factor that
      regulates the expression of estrogen-responsive genes. A key step in the
      activation process is the initial binding of the ER dimer to the estrogen
      response element (ERE). We examined the effect of the coactivator proteins, HMGB1
      and HMGB2, in enhancing ER binding affinity to single and tandem EREs. Using
      EMSAs, both HMGB proteins are shown to enhance ER binding and induce cooperative
      ER binding on tandem ERE elements. We demonstrate that HMGB proteins facilitate
      strong ER binding to ERE consensus half-sites, exhibiting binding affinities
      comparable with ER binding to consensus ERE in the absence of HMGB proteins.
      These findings reveal that although HMGB proteins enhance binding affinity, they
      also relax ER binding specificity. Deoxyribonuclease I footprinting demonstrates
      that ER binds very differently to consensus ERE and ERE consensus half-sites,
      whereas both deoxyribonuclease I and exonuclease III digestions show that the
      presence of HMGB1/2 does not alter the DNA protection in ER/ERE complexes.
      Protease digestions of the complexes support this conclusion and show that a
      global conformation change occurs in ER when bound to the different ER binding
      sites. Models for these interactions are discussed, together with a hit-and-run
      mechanism that HMGB proteins may utilize to produce these effects.

PMID- 15256537
TI  - Genomic organization of mouse orexin receptors: characterization of two novel
      tissue-specific splice variants.
AB  - In humans and rat, orexins orchestrate divergent actions through their G protein
      coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Orexins also play an
      important physiological role in mouse, but the receptors through which they
      function are not characterized. To characterize the physiological role(s) of
      orexins in the mouse, we cloned and characterized the mouse orexin receptor(s),
      mOX1R and mOX2R, using rapid amplification of cDNA (mouse brain) ends, RT-PCR,
      and gene structure analysis. The mOX1R cDNA encodes a 416-amino acid (aa)
      receptor. We have identified two alternative C terminus splice variants of the
      mOX2R; mOX2 alpha R (443 aa) and mOX2 beta R (460 aa). Binding studies in human
      embryonic kidney 293 cells transfected with mOX1R, mOX2 alpha R, and the mOX2
      beta R revealed specific, saturable sites for both orexin-A and -B. Activation of
      these receptors by orexins induced inositol triphosphate (IP(3)) turnover.
      However, human embryonic kidney 293 cells transfected with mOXRs demonstrated no
      cAMP response to either orexin-A or orexin-B challenge, although forskolin and
      GTP gamma S revealed a dose-dependent increase in cAMP. Although, orexin-A and -B
      showed no difference in binding characteristics between the splice variants;
      interestingly, orexin-B led to an increase in IP(3) production at all
      concentrations in the mOX2 beta R variant. Orexin-A, however, showed no
      difference in IP(3) production between the two variants. Additionally, in the
      mouse, we demonstrate that these splice variants are distributed in a tissue
      specific manner, where OX2 alpha R mRNA was undetectable in skeletal muscle and
      kidney. Moreover, food deprivation led to a greater increase in hypothalamic mOX2
      beta R gene expression, compared with both mOX1R and mOX2 alpha R. This
      potentially implicates a fundamental physiological role for these splice
      variants.

PMID- 15256538
TI  - In vivo pharmacological characterization of indiplon, a novel pyrazolopyrimidine
      sedative-hypnotic.
AB  - Indiplon (NBI 34060; N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5
      alpha]pyrimidin-7-yl]phenyl]acetamide), a novel pyrazolopyrimidine and high
      affinity allosteric potentiator of GABA(A) receptor function, was profiled for
      its effects in rodents after oral administration. In mice, indiplon inhibited
      locomotor activity (ED(50) = 2.7 mg/kg p.o.) at doses lower than the
      nonbenzodiazepine hypnotics zolpidem (ED(50) = 6.1 mg/kg p.o.) and zaleplon
      (ED(50) = 24.6 mg/kg p.o.), a sedative effect that was reversed by the
      benzodiazepine site antagonist flumazenil. Indiplon inhibited retention in the
      mouse passive avoidance paradigm over a dose range and with a temporal profile
      that coincided with its sedative activity. Indiplon, zolpidem, and zaleplon were
      equally effective in inhibiting locomotor activity in the rat and produced dose
      related deficits on the rotarod. In a rat vigilance paradigm, indiplon, zolpidem,
      and zaleplon produced performance deficits over a dose range consistent with
      their sedative effects, although indiplon alone showed no significant increase in
      response latency. Indiplon produced a small deficit in the delayed nonmatch to
      sample paradigm at a dose where sedative effects became apparent. Indiplon was
      active in the rat Vogel test of anxiety, but it showed only a sedative profile in
      the mouse open field test. The pharmacokinetic profile of indiplon in both rat
      and mouse was consistent with its pharmacodynamic properties and indicated a
      rapid T(max), short t(1/2), and excellent blood-brain barrier penetration.
      Therefore, indiplon has the in vivo profile of an efficacious sedative-hypnotic,
      in agreement with its in vitro receptor pharmacology as a high-affinity
      allosteric potentiator of GABA(A) receptor function, with selectivity for alpha1
      subunit-containing GABA(A) receptors.

PMID- 15256539
TI  - The NR2B-selective N-methyl-D-aspartate receptor antagonist Ro 25-6981 [(+/-)
      (R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine
      propanol] potentiates the effect of nicotine on locomotor activity and dopamine
      release in the nucleus accumbens.
AB  - It has been proposed that nicotine-stimulated locomotor activity (LMA) and
      nicotine-induced dopamine (DA) release in the mesocorticolimbic DA system is
      partly regulated by glutamate receptors, particularly N-methyl-D-aspartate (NMDA)
      receptors. The functional characteristics of NMDA receptors depend on their
      subunit composition (NR1 in combination with NR2A-D). In the present study, we
      investigated the effect of the NR2B-selective NMDA receptor antagonist Ro 25-6981
      [(+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine
      propanol] on nicotine-stimulated LMA and nicotine-induced DA release in the
      nucleus accumbens (NAcc) in rats. Ro 25-6981 (3 and 10 mg/kg i.p.) given 10 min
      prior to a high dose (0.6 mg/kg s.c.) or a subthreshold dose (0.1 mg/kg s.c.) of
      nicotine potentiated nicotine-stimulated LMA with no effect when administered
      alone. Similarly, administration of a low dose (0.05 mg/kg i.p.) of the
      noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate) had no
      effect on LMA by itself but potentiated nicotine-induced (0.1 mg/kg) LMA.
      However, pretreatment with the competitive NMDA receptor antagonist CGP39551 [(E)
      (+/-)-2-amino-4-methyl-5-phosphono-3-pentenoic acid ethyl ester] (10 mg/kg i.p.)
      did not potentiate the LMA effect of 0.1 mg/kg nicotine as seen with Ro 25-6981.
      In vivo microdialysis revealed a significant increase of DA release in the NAcc
      in response to nicotine (0.1 mg/kg s.c.). In analogy to our LMA data, Ro 25-6981
      (10 mg/kg i.p.) significantly potentiated the nicotine-induced DA release,
      although it had no effect on DA release when given alone. The data suggest that,
      compared with other subunits of the NMDA receptor, the NR2B subunit might play a
      different role in the reinforcing effects of nicotine.

PMID- 15256540
TI  - Characterization of the interaction of indiplon, a novel pyrazolopyrimidine
      sedative-hypnotic, with the GABAA receptor.
AB  - Clinically used benzodiazepine and nonbenzodiazepine sedative-hypnotic agents for
      the treatment of insomnia produce their therapeutic effects through allosteric
      enhancement of the effects of the inhibitory neurotransmitter GABA at the GABA(A)
      receptor. Indiplon is a novel pyrazolopyrimidine sedative-hypnotic agent,
      currently in development for insomnia. Using radioligand binding studies,
      indiplon inhibited the binding of [(3)H]Ro 15-1788 (flumazenil) to rat cerebellar
      and cerebral cortex membranes with high affinity (K(i) values of 0.55 and 0.45
      nM, respectively). [(3)H]Indiplon binding to rat cerebellar and cerebral cortex
      membranes was reversible and of high affinity, with K(D) values of 1.01 and 0.45
      nM, respectively, with a pharmacological specificity consistent with preferential
      labeling of GABA(A) receptors containing alpha1 subunits. In "GABA shift"
      experiments and in measurements of GABA-induced chloride conductance in rat
      cortical neurons in culture, indiplon behaved as an efficacious potentiator of
      GABA(A) receptor function. In both the radioligand binding and
      electrophysiological experiments, indiplon had a higher affinity than zolpidem or
      zaleplon. These in vitro properties are consistent with the in vivo properties of
      indiplon as an effective sedative-hypnotic acting through allosteric potentiation
      of the GABA(A) receptor.

PMID- 15256543
TI  - Genome Update: annotation quality in sequenced microbial genomes.

PMID- 15256541
TI  - Exploration of the conserved A+C wobble pair within the ribosomal peptidyl
      transferase center using affinity purified mutant ribosomes.
AB  - Protein synthesis in the ribosome's large subunit occurs within an active site
      comprised exclusively of RNA. Mutational studies of rRNA active site residues
      could provide valuable insight into the mechanism of peptide bond formation, but
      many of these mutations cause a dominant lethal phenotype, which prevents
      production of the homogeneous mutant ribosomes needed for analysis. We report a
      general method to affinity purify in vivo assembled 50S ribosomal subunits
      containing lethal active site mutations via a U1A protein-binding tag inserted
      onto the 23S rRNA. The expected pH-dependent formation of the A2450+C2063 wobble
      pair has made it a potential candidate for the pH-dependent conformational change
      that occurs within the ribosomal active site. Using this approach, the active
      site A2450+C2063 pair was mutated to the isosteric, but pH-independent,
      G2450*U2063 wobble pair, and 50S subunits containing the mutations were affinity
      purified. The G*U mutation caused the adjacent A2451 to become hyper-reactive to
      dimethylsulfate (DMS) modification in a pH-independent manner. Furthermore, the
      G*U mutation decreased both the rate of peptide bond formation and the affinity
      of the post-translocation complex for puromycin. The reaction rate (k(pep)) was
      reduced approximately 200-fold for both puromycin and the natural aminoacyl-tRNA
      A-site substrate. The mutations also substantially altered the pH dependence of
      the reaction. Mutation of this base pair has significant deleterious effects upon
      peptidyl transferase activity, but because G*U mutation disrupts several tertiary
      contacts with the wobble pair, the assignment of A2450 as the active site residue
      with the neutral pK(a) important for the peptidyl transferase reaction cannot be
      fully supported or excluded based upon these data.

PMID- 15256544
TI  - Bacterial whole-genome sequences: minimal information and strain availability.

PMID- 15256542
TI  - RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages
      on DNA unwinding by BLM and WRN helicases.
AB  - Bloom (BLM) and Werner (WRN) syndrome proteins are members of the RecQ family of
      SF2 DNA helicases. In this paper, we show that restricting the rotational DNA
      backbone flexibility, by introducing vinylphosphonate internucleotide linkages in
      the translocating DNA strand, inhibits efficient duplex unwinding by these
      enzymes. The human single-stranded DNA binding protein replication protein A
      (RPA) fully restores the unwinding activity of BLM and WRN on vinylphosphonate
      containing substrates while the heterologous single-stranded DNA binding protein
      from Escherichia coli (SSB) restores the activity only partially. Both RPA and
      SSB fail to restore the unwinding activity of the SF1 PcrA helicase on modified
      substrates, implying specific interactions of RPA with the BLM and WRN helicases.
      Our data highlight subtle differences between SF1 and SF2 helicases and suggest
      that although RecQ helicases belong to the SF2 family, they are mechanistically
      more similar to the SF1 PcrA helicase than to other SF2 helicases that are not
      affected by vinylphosphonate modifications.

PMID- 15256545
TI  - Genetic clues on the evolution of anaerobic catabolism of aromatic compounds.

PMID- 15256546
TI  - Communications blackout? Do N-acylhomoserine-lactone-degrading enzymes have any
      role in quorum sensing?
AB  - A number of bacteria, including some significant pathogens, utilize N
      acylhomoserine lactones (AHLs) as quorum sensing signals. There is considerable
      interest in the therapeutic potential of disrupting quorum sensing. Recently, a
      number of bacteria have been identified which are capable of enzymic inactivation
      of AHLs. These enzymes show considerable promise as 'quenchers' of quorum
      sensing. However, the assumption that the natural function of these enzymes is to
      disrupt or modulate quorum sensing has yet to be established. This review surveys
      the progress made to date in this field and examines what implications these
      findings have for our understanding of the role played by these enzymes in vivo.

PMID- 15256547
TI  - Fungal cell wall chitinases and glucanases.
AB  - The fungal cell wall is a complex structure composed of chitin, glucans and other
      polymers, and there is evidence of extensive cross-linking between these
      components. The wall structure is highly dynamic, changing constantly during cell
      division, growth and morphogenesis. Hydrolytic enzymes, closely associated with
      the cell wall, have been implicated in the maintenance of wall plasticity and may
      have roles during branching and cross-linking of polymers. Most fungal cell wall
      hydrolases identified to date have chitinase or glucanase activity and this short
      article reviews the apparent functions of these enzymes in unicellular and
      filamentous fungi, and the mechanisms that regulate enzyme activity in yeasts.

PMID- 15256548
TI  - A global role for Fis in the transcriptional control of metabolism and type III
      secretion in Salmonella enterica serovar Typhimurium.
AB  - Fis is a key DNA-binding protein involved in nucleoid organization and modulation
      of many DNA transactions, including transcription in enteric bacteria. The
      regulon of genes whose expression is influenced by Fis in Salmonella enterica
      serovar Typhimurium (S. typhimurium) has been defined by DNA microarray analysis.
      These data suggest that Fis plays a central role in coordinating the expression
      of both metabolic and type III secretion factors. The genes that were most
      strongly up-regulated by Fis were those involved in virulence and located in the
      pathogenicity islands SPI-1, SPI-2, SPI-3 and SPI-5. Similarly, motility and
      flagellar genes required Fis for full expression. This was shown to be a direct
      effect as purified Fis protein bound to the promoter regions of representative
      flagella and SPI-2 genes. Genes contributing to aspects of metabolism known to
      assist the bacterium during survival in the mammalian gut were also Fis
      regulated, usually negatively. This category included components of metabolic
      pathways for propanediol utilization, biotin synthesis, vitamin B(12) transport,
      fatty acids and acetate metabolism, as well as genes for the glyoxylate bypass of
      the tricarboxylic acid cycle. Genes found to be positively regulated by Fis
      included those for ethanolamine utilization. The data reported reveal the central
      role played by Fis in coordinating the expression of both housekeeping and
      virulence factors required by S. typhimurium during life in the gut lumen or
      during systemic infection of host cells.

PMID- 15256549
TI  - The SPI2-encoded SseA chaperone has discrete domains required for SseB
      stabilization and export, and binds within the C-terminus of SseB and SseD.
AB  - SseA, a key Salmonella virulence determinant, is a small, basic pI protein
      encoded within the Salmonella pathogenicity island 2 and serves as a type III
      secretion system chaperone for SseB and SseD. Both SseA partners are subunits of
      the surface-localized translocon module that delivers effectors into the host
      cell; SseB is predicted to compose the translocon sheath and SseD is a putative
      translocon pore subunit. In this study, SseA molecular interactions with its
      partners were characterized further. Yeast two-hybrid screens indicate that SseA
      binding requires a C-terminal domain within both partners. An additional central
      domain within SseD was found to influence binding. The SseA-binding region within
      SseB was found to encompass a predicted amphipathic helix of a type participating
      in coiled-coil interactions that are implicated in the assembly of translocon
      sheaths. Deletions that impinge upon this putative coiled-coiled domain prevent
      SseA binding, suggesting that SseA occupies a portion of the coiled-coil. SseA
      occupancy of this motif is envisioned to be sufficient to prevent premature SseB
      self-association inside bacteria. Domain mapping on the chaperone was also
      performed. A deletion of the SseA N-terminus, or site-directed mutations within
      this region, allowed stabilization of SseB, but its export was disrupted.
      Therefore, the N-terminus of SseA provides a function that is essential for SseB
      export, but dispensable for partner binding and stabilization.

PMID- 15256550
TI  - A family of putative MSCRAMMs from Enterococcus faecalis.
AB  - The recently published Enterococcus faecalis genome [Paulsen, I. T., Banerjei,
      L., Myers, G. S. & 29 other authors (2003). Science 299, 2071-2074)] was examined
      and 41 putative cell-wall-anchored proteins were identified. Seventeen of these
      proteins are predicted to contain tandemly repeated immunoglobulin-like folds
      characteristic of the structural organization of staphylococcal adhesins of the
      MSCRAMM (microbial surface component recognizing adhesive matrix molecules) type.
      Two of the nine proteins selected for further study appear to represent cell-wall
      anchored enzymes. It is proposed that the remaining seven proteins constitute a
      family of structurally related proteins potentially interacting with proteins of
      the host. This family includes the previously identified collagen/laminin-binding
      MSCRAMM ACE [Rich, R. L., Kreikemeyer, B., Owens, R. T., LaBrenz, S., Narayana,
      S. V., Weinstock, G. M., Murray, B. E. & Hook, M. (1999). J Biol Chem 274, 26939
      26945]. It is further demonstrated that genes encoding the seven putative
      MSCRAMMs are present in all E. faecalis strains tested and these proteins appear
      to be expressed during infection in humans, since sera from infected individuals
      contain antibodies reacting with recombinant versions of the enterococcal
      proteins.

PMID- 15256551
TI  - The bifunctional peptidoglycan lysin of Streptococcus agalactiae bacteriophage
      B30.
AB  - A group B streptococcal (GBS) bacteriophage lysin gene was cloned and expressed
      in Escherichia coli. The purified recombinant enzyme, calculated to have a
      molecular mass of 49 677 Da, lysed GBS cells. The susceptibility of GBS cells to
      lysis by the enzyme depended upon the growth stage at which they were harvested,
      with early exponential phase cells most sensitive. Calcium ions enhanced the
      activity of the enzyme. The enzyme also lysed other beta-haemolytic streptococci,
      including groups A, C, E and G streptococci, but not common oral streptococci,
      including Streptococcus mutans. The generation of both reducing activity and N
      terminal alanine residues during lysis indicated that the lysin is a bifunctional
      enzyme, possessing both glycosidase and endopeptidase activities. This is
      consistent with the presence of two conserved sequence domains, an Acm
      (acetylmuramidase) domain associated with lysozyme activity, and a CHAP
      (cysteine, histidine-dependent amidohydrolases/peptidases) domain associated with
      endopeptidase activity. Site-directed mutagenesis of conserved cysteine and
      histidine residues in the CHAP domain and conserved aspartate and glutamate
      residues in the Acm domain confirmed their importance for lysozyme and
      endopeptidase activity respectively.

PMID- 15256552
TI  - Three genes, lgtF, lic2C and lpsA, have a primary role in determining the pattern
      of oligosaccharide extension from the inner core of Haemophilus influenzae LPS.
AB  - Lipopolysaccharide (LPS) is a virulence determinant of Haemophilus influenzae and
      exhibits substantial heterogeneity in structure within and between strains. Key
      factors contributing to this heterogeneity are the genes required to add the
      first glycose to each of the three heptose residues of the LPS inner core. In
      each case this addition can facilitate further oligosaccharide extension. lgtF is
      invariably present in strains and the product has a function in adding the
      glucose to the first heptose. lic2C is present in half the strains and was found
      to add a glucose to the second heptose. Insertion of lic2C into a strain that
      does not naturally contain it resulted in hexose incorporation from the second
      heptose of the LPS. The product of the lpsA gene can add a glucose or galactose
      to the third heptose. By allelic replacement of lpsA between strains it is shown
      that the sequence of the gene can be the sole determinant of this specificity.
      Thus, lgtF, lic2C and lpsA make significant but very distinct contributions to
      the conservation and variable patterns of oligosaccharide extensions seen in H.
      influenzae LPS.

PMID- 15256554
TI  - Regulation of the expression of the Acidithiobacillus ferrooxidans rus operon
      encoding two cytochromes c, a cytochrome oxidase and rusticyanin.
AB  - The regulation of the expression of the rus operon, proposed to encode an
      electron transfer chain from the outer to the inner membrane in the obligate
      acidophilic chemolithoautroph Acidithiobacillus ferrooxidans, has been studied at
      the RNA and protein levels. As observed by Northern hybridization, real-time PCR
      and reverse transcription analyses, this operon was more highly expressed in
      ferrous iron- than in sulfur-grown cells. Furthermore, it was shown by
      immunodetection that components of this respiratory chain are synthesized in
      ferrous iron- rather than in sulfur-growth conditions. Nonetheless, weak
      transcription and translation products of the rus operon were detected in sulfur
      grown cells at the early exponential phase. The results strongly support the
      notion that rus-operon expression is induced by ferrous iron, in agreement with
      the involvement of the rus-operon-encoded products in the oxidation of ferrous
      iron, and that ferrous iron is used in preference to sulfur.

PMID- 15256553
TI  - Biochemical and molecular characterization of Lactobacillus reuteri 121
      reuteransucrase.
AB  - Lactobacillus reuteri strain 121 uses sucrose for synthesis of a unique, soluble
      glucan ('reuteran') with mainly alpha-(1-->4) glucosidic linkages. The gene
      (gtfA) encoding this glucansucrase enzyme had previously been characterized.
      Here, a detailed biochemical and molecular analysis of the GTFA enzyme is
      presented. This is believed to be the first report describing reuteransucrase
      enzyme kinetics and the oligosaccharides synthesized with various acceptors.
      Alignments of the GTFA sequence with glucansucrases from Streptococcus and
      Leuconostoc identified conserved amino-acid residues in the catalytic core
      critical for enzyme activity. Mutants Asp1024Asn, Glu1061Gln and Asp1133Asn
      displayed 300- to 1000-fold-reduced specific activities. To investigate the role
      of the relatively large N-terminal variable domain (702 amino acids) and the
      relatively short C-terminal putative glucan-binding domain (267 amino acids, with
      11 YG repeats), various truncated derivatives of GTFA (1781 amino acids) were
      constructed and characterized. Deletion of the complete N-terminal variable
      domain of GTFA (GTFA-Delta N) had little effect on reuteran characteristics
      (size, distribution of glycosidic linkages), but the initial transferase activity
      of the mutant enzyme increased drastically. Sequential C-terminal deletions (up
      to six YG repeats) in GTFA-Delta N also had little effect on reuteran
      characteristics. However, enzyme kinetics drastically changed. Deletion of 7, 8
      or 11 YG repeats resulted in dramatic loss of total enzyme activity (43-, 63- and
      1000-fold-reduced specific activities, respectively). Characterization of
      sequential C-terminal deletion mutants of GTFA-Delta N revealed that the C
      terminal domain of reuteransucrase has an important role in glucan binding.

PMID- 15256555
TI  - Transcriptional regulation of the Bacteroides fragilis ferritin gene (ftnA) by
      redox stress.
AB  - This study shows that the iron-storage protein ferritin is a component of the
      redox-stress response in the obligate anaerobe Bacteroides fragilis. It is up
      regulated at transcriptional level under aerobic conditions but constitutively
      expressed at low levels under anaerobic conditions. Northern hybridization and
      primer extension analysis revealed that ftnA is transcribed as a monocistronic
      mRNA of approximately 600 nt. Under reduced anaerobic conditions, ftnA mRNA
      levels were not dependent on the iron content of the culture medium. Following
      oxygen exposure ftnA message increased about 10-fold in iron-replete medium
      compared to a fourfold increase under low-iron conditions. Addition of the
      oxidant potassium ferricyanide induced expression of ftnA mRNA anaerobically,
      suggesting that the oxidation of the medium affected expression of ftnA. Two
      transcription initiation start sites were identified. Both transcripts were
      expressed constitutively under anaerobic conditions but one promoter was induced
      by oxidative stress or the addition of the oxidant potassium ferricyanide. The
      effect of redox stress on ftnA expression was further investigated by addition of
      diamide, a thiol-oxidizing agent, which induced ftnA mRNA levels anaerobically,
      suggesting that an unbalanced cellular redox state also affects ftnA expression.
      Induction by hydrogen peroxide and oxygen was decreased in an oxyR deletion
      mutant but some oxygen induction still occurred. This strongly suggests that ftnA
      is regulated by both the peroxide response transcriptional activator, OxyR, and
      another unidentified oxygen-dependent regulator. Taken together, these data show
      that ftnA mRNA levels are controlled by both iron and oxidative stress; this
      coordinated regulation may be important for survival in an adverse aerobic
      environment.

PMID- 15256556
TI  - Autophosphorylation of the 16 kDa and 70 kDa antigens (Hsp 16.3 and Hsp 70) of
      Mycobacterium tuberculosis.
AB  - Several antigens of Mycobacterium tuberculosis, identified by monoclonal
      antibodies, have been previously cloned and are being exploited in the
      development of improved vaccines and diagnostic reagents. In this study, the
      molecular characteristics of two of these antigens, the immunodominant proteins
      Hsp 16.3 and Hsp 70, were analysed in further detail by assessing their capacity
      to undergo protein phosphorylation, a chemical modification frequently used by
      organisms to adjust to environmental variations. Hsp 16.3 was overproduced in an
      Escherichia coli expression system and purified to homogeneity. Upon incubation
      in the presence of radioactive ATP, it was shown to possess autophosphorylation
      activity. Two-dimensional analysis of its phosphoamino acid content revealed that
      it was modified exclusively at serine residues. In addition, cross-linking
      experiments demonstrated that it could tightly bind to ATP. Purified Hsp 70 was
      also shown to autophosphorylate but phosphorylation occurred exclusively at
      threonine residues. This reaction was found to be strongly stimulated by calcium
      ions. These data indicate that both structural and functional similarities exist
      between Hsp 16.3 (Acr) and alpha-crystallin, a eukaryotic protein which plays an
      important role in maintaining the transparency of the vertebrate eye, and that
      the functional properties of Hsp 70 from M. tuberculosis are similar to those of
      other bacterial members of the Hsp 70 family, particularly the E. coli homologue
      DnaK.

PMID- 15256557
TI  - A two-plasmid system for stable, selective-pressure-independent expression of
      multiple extracellular proteins in mycobacteria.
AB  - Recombinant mycobacteria expressing Mycobacterium tuberculosis extracellular
      proteins are leading candidates for new vaccines against tuberculosis and other
      mycobacterial diseases, and important tools both in antimycobacterial drug
      development and basic research in mycobacterial pathogenesis. Recombinant
      mycobacteria that stably overexpress and secrete major extracellular proteins of
      M. tuberculosis in native form on plasmids pSMT3 and pNBV1 were previously
      constructed by the authors. To enhance the versatility of this plasmid-based
      approach for mycobacterial protein expression, the Escherichia coli/mycobacteria
      shuttle plasmid pGB9 was modified to accommodate mycobacterial genes expressed
      from their endogenous promoters. Previous studies showed that the modified
      plasmid, designated pGB9.2, derived from the cryptic Mycobacterium fortuitum
      plasmid pMF1, was present at a low copy number in both E. coli and mycobacteria,
      and expression of recombinant M. tuberculosis proteins was found to be at levels
      paralleling its copy number, that is, approximating their endogenous levels.
      Plasmid pGB9.2 was compatible with the shuttle vectors pSMT3 and pNBV1 and in
      combination with them it simultaneously expressed the M. tuberculosis 30 kDa
      extracellular protein FbpB. Plasmid pGB9.2 was stably maintained in the absence
      of selective pressure in three mycobacterial species: Mycobacterium bovis BCG, M.
      tuberculosis and M. smegmatis. Plasmid pGB9.2 was found to be self-transmissible
      between both fast- and slow-growing mycobacteria, but not from mycobacteria to E.
      coli or between E. coli strains. The combination of two compatible plasmids in
      one BCG strain allows expression of recombinant mycobacterial proteins at
      different levels, a potentially important factor in optimizing vaccine potency.

PMID- 15256558
TI  - Structure-function relationships of UMP kinases from pyrH mutants of Gram
      negative bacteria.
AB  - Bacterial uridine monophosphate (UMP) kinases are essential enzymes encoded by
      pyrH genes, and conditional-lethal or other pyrH mutants were analysed with
      respect to structure-function relationships. A set of thermosensitive pyrH
      mutants from Escherichia coli was generated and studied, along with already
      described pyrH mutants from Salmonella enterica serovar Typhimurium. It is shown
      that Arg-11 and Gly-232 are key residues for thermodynamic stability of the
      enzyme, and that Asp-201 is important for both catalysis and allosteric
      regulation. A comparison of the amino acid sequence of UMP kinases from several
      prokaryotes showed that these were conserved residues. Discussion on the enzyme
      activity level in relation to bacterial viability is also presented.

PMID- 15256559
TI  - DNA-containing membrane vesicles of Pseudomonas aeruginosa PAO1 and their genetic
      transformation potential.
AB  - Natural membrane vesicles (n-MVs) produced by Pseudomonas aeruginosa PAO1 and
      PAO1 carrying plasmid pAK1900 (p-MVs) were purified and analysed for DNA content.
      The MVs were isolated by a procedure designed to ensure no cellular contamination
      from the parent MV-producing cells. Fluorometry analysis revealed that p-MVs were
      associated with 7.80 ng DNA (20 microg MV protein)(-1). PCR analysis using
      specific primers for pAK1900 sequences and a chromosomal target, oprL, indicated
      that only plasmid DNA was contained within the lumen of p-MVs after exogenous DNA
      was digested by DNase. MVs have previously been shown to be capable of fusing
      into the outer membrane (OM) of PAO1 and Escherichia coli DH5 alpha. Accordingly,
      p-MVs should deliver the plasmid into the periplasm, where it would only have to
      by-pass the plasma membrane (PM) for effective transformation. It was speculated
      that p-MVs should increase transformation efficiency but the data suggested
      otherwise. p-MVs did not transform PAO1 nor DH5 alpha under a variety of
      transforming conditions. To characterize p-MVs and to ensure that membrane
      encapsulated pAK1900 was not derived from a small proportion of lysed cells
      within the culture and bound by PM instead of OM, which typically forms n-MVs,
      the physical and ultrastructural differences between n- and p-MVs were
      determined. Cryo-transmission electron microscopy (cryo-TEM) revealed that n-MVs
      and p-MVs closely resembled isolated OM. Buoyant density measurements using
      isopycnic sucrose gradients on isolated PM, OM, n- and p-MVs demonstrated that
      isolated OM and n-MVs both fractionated into two bands (rho=1.240 and 1.260 g ml(
      1)). p-MVs also produced two bands but at two different densities (rho=1.250 and
      1.265 g ml(-1)) which may be attributed to the presence of DNA. SDS-PAGE showed
      that p-MVs possessed most major OM proteins and also contained 43.70 nmol 3-deoxy
      d-manno-octulosonic acid (KDO) (mg protein)(-1) as an LPS marker. The amount of
      NADH oxidase activity, a PM enzyme, in the p-MVs was barely detectable. These
      data strongly suggest that p-MVs are OM-based, with little if any PM material
      associated with them. The possibility of whether exogenous plasmid DNA could
      enter n-MVs once the vesicles had departed from cells was also tested;
      surprisingly, a small amount of DNA could. Accordingly, the data suggest that DNA
      can be taken up by MVs using two separate routes: (1) via a periplasmic route and
      (2) via an extracellular, exogenous route.

PMID- 15256560
TI  - HthA, a putative DNA-binding protein, and HthB are important for fruiting body
      morphogenesis in Myxococcus xanthus.
AB  - In response to starvation, Myxococcus xanthus initiates a developmental programme
      that results in the formation of spore-filled multicellular fruiting bodies.
      Fruiting body formation depends on the temporal and spatial coordination of
      aggregation and sporulation and involves temporally and spatially coordinated
      changes in gene expression. This paper reports the identification of two genes,
      hthA and hthB, that are important for fruiting body formation. hthA and hthB are
      co-transcribed, and transcription of the two genes decreases strongly during
      development. Loss of HthA and HthB function results in delayed aggregation, a
      reduction in the level of sporulation, and abnormal developmental gene
      expression. Extracellular complementation experiments showed that the
      developmental defects caused by loss of HthA and HthB function are not due to the
      inability to synthesize an intercellular signal required for fruiting body
      formation. HthA, independent of HthB, is required for aggregation. HthB, alone or
      in combination with HthA, is required for sporulation. HthA is predicted to
      contain a C-terminal helix-turn-helix DNA-binding domain. Intriguingly, the N
      terminal part of HthA does not exhibit significant amino acid similarity to
      proteins in the databases. The HthB protein lacks homologues in the databases.
      The results suggest that HthA is a novel DNA-binding protein, which regulates
      transcription of genes important for aggregation, and that HthB, alone or in
      combination with HthA, stimulates sporulation.

PMID- 15256561
TI  - Identification and characterization of two alpha-1,6-mannosyltransferases, Anl1p
      and Och1p, in the yeast Yarrowia lipolytica.
AB  - In this study, the identification and characterization of the Yarrowia lipolytica
      homologues of Saccharomyces cerevisiae alpha-1,6-mannosyltransferases Anp1p and
      Och1p, designated YlAnl1p and YlOch1p, are described. In order to confirm the
      function of the Y. lipolytica proteins, including the previously isolated
      YlMnn9p, in the N-glycosylation pathway, a phenotypic analysis of the disrupted
      strains Delta Ylmnn9, Delta Ylanl1, Delta Yloch1, Delta Ylanl1 Delta Ylmnn9 and
      Delta Ylmnn9 Delta Yloch1 was performed. Disruption of the YlMNN9, YlANL1 and
      YlOCH1 genes caused an increased sensitivity to SDS, compatible with a
      glycosylation defect, and to Calcofluor White, characteristic of cell-wall
      defects. Moreover, Western-blot analysis of a heterologous glycosylated protein
      confirmed a direct role of YlMnn9p and YlAnl1p in the N-glycosylation process.
      These mutant strains, Delta Ylmnn9, Delta Ylanl1, Delta Yloch1, Delta Ylanl1
      Delta Ylmnn9 and Delta Ylmnn9 Delta Yloch1 may thus be used to establish a model
      for the Y. lipolytica N-linked glycosylation pathway.

PMID- 15256562
TI  - The CaCTR1 gene is required for high-affinity iron uptake and is
      transcriptionally controlled by a copper-sensing transactivator encoded by
      CaMAC1.
AB  - The ability of Candida albicans to acquire iron from the hostile environment of
      the host is known to be necessary for virulence and appears to be achieved using
      a similar system to that described for Saccharomyces cerevisiae. In S.
      cerevisiae, high-affinity iron uptake is dependent upon the acquisition of
      copper. The authors have previously identified a C. albicans gene (CaCTR1) that
      encodes a copper transporter. Deletion of this gene results in a mutant strain
      that grows predominantly as pseudohyphae and displays aberrant morphology in low
      copper conditions. This paper demonstrates that invasive growth by C. albicans is
      induced by low-copper conditions and that this is augmented in a Cactr1-null
      strain. It also shows that deletion of CaCTR1 results in defective iron uptake.
      In S. cerevisiae, genes that facilitate high-affinity copper uptake are
      controlled by a copper-sensing transactivator, ScMac1p. The authors have now
      identified a C. albicans gene (CaMAC1) that encodes a copper-sensing
      transactivator. A Camac1-null mutant displays phenotypes similar to those of a
      Cactr1-null mutant and has no detectable CaCTR1 transcripts in low-copper
      conditions. It is proposed that high-affinity copper uptake by C. albicans is
      necessary for reductive iron uptake and is transcriptionally controlled by
      CaMac1p in a similar manner to that in S. cerevisiae.

PMID- 15256563
TI  - Functional analysis of the ALD gene family of Saccharomyces cerevisiae during
      anaerobic growth on glucose: the NADP+-dependent Ald6p and Ald5p isoforms play a
      major role in acetate formation.
AB  - In Saccharomyces cerevisiae, acetate is formed by acetaldehyde dehydrogenase
      (ACDH), a key enzyme of the pyruvate dehydrogenase (PDH) bypass, which fulfils
      the essential task of generating acetyl-CoA in the cytosol. The role of the five
      members of the ACDH family (ALD genes) was investigated during anaerobic growth
      on glucose. Single and multiple ald Delta mutants were generated in the wine
      yeast-derived V5 and laboratory CEN.PK strains and analysed under standard (YPD 5
      % glucose) and wine (MS 20 % glucose) fermentation conditions. The deletion of
      ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the
      first time that the mitochondrial Ald5p isoform is involved in the biosynthesis
      of acetate during anaerobic growth on glucose. Acetate production of the ald4
      Delta mutant was slightly decreased in the CEN.PK strain during growth on YPD
      only. In contrast, the deletion of ALD2 or ALD3 had no effect on acetate
      production. The absence of Ald6p was compensated by the mitochondrial isoforms
      and this involves the transcriptional activation of ALD4. Consistent with this,
      growth retardation was observed in ald6 Delta ald4 Delta, and this effect was
      amplified by the additional deletion of ALD5. A ald Delta null mutant, devoid of
      ACDH activity, was viable and produced similar levels of acetate to the ald6
      Delta ald4 Delta ald5 Delta strain, excluding a role of Ald2p and Ald3p. Thus,
      acetate is mainly produced by the cytosolic PDH bypass via Ald6p and by a
      mitochondrial route involving Ald5p. An unknown alternative pathway can
      compensate for the loss of Ald6p, Ald4p and Ald5p.

PMID- 15256564
TI  - Ancient genes of Saccharomyces cerevisiae.
AB  - Amber is a plant resin mainly produced by coniferous trees that, after entrapping
      a variety of living beings, was subjected to a process of fossilization until it
      turned into yellowish, translucent stones. It is also one of the best sources of
      ancient DNA on which to perform studies on evolution. Here a method for the
      sterilization of amber that allows reliable ancient DNA extraction with no actual
      DNA contamination is described. Working with insects taken from amber, it was
      possible to amplify the ATP9, PGU1 and rRNA18S ancient genes of Saccharomyces
      cerevisiae corresponding to samples from the Miocene and Oligocene. After
      comparison of the current genes with their ancient (up to 35-40 million years)
      counterparts it was concluded that essential genes such as rRNA18S are highly
      conserved and that even normal 'house-keeping' genes, such as PGU1, are
      strikingly conserved along the millions of years that S. cerevisiae has evolved.

PMID- 15256565
TI  - Symbionts of the gut flagellate Staurojoenina sp. from Neotermes cubanus
      represent a novel, termite-associated lineage of Bacteroidales: description of
      'Candidatus Vestibaculum illigatum'.
AB  - The symbioses between cellulose-degrading flagellates and bacteria are one of the
      most fascinating phenomena in the complex micro-ecosystem found in the hindgut of
      lower termites. However, little is known about the identity of the symbionts. One
      example is the epibiotic bacteria colonizing the surface of hypermastigote
      protists of the genus Staurojoenina. By using scanning electron microscopy, it
      was shown that the whole surface of Staurojoenina sp. from the termite Neotermes
      cubanus is densely covered with long rod-shaped bacteria of uniform size and
      morphology. PCR amplification of 16S rRNA genes from isolated protozoa and
      subsequent cloning yielded a uniform collection of clones with virtually
      identical sequences. Phylogenetic analysis placed them as a new lineage among the
      Bacteroidales, only distantly related to other uncultivated bacteria in the
      hindgut of other termites, including an epibiont of the flagellate Mixotricha
      paradoxa. The closest cultivated relative was Tannerella forsythensis (<85 %
      sequence identity). Fluorescence in situ hybridization with a newly designed
      clone-specific oligonucleotide probe confirmed that these sequences belong to the
      rod-shaped epibionts of Staurojoenina sp. Transmission electron microscopy
      confirmed the presence of a Gram-negative cell wall and revealed special
      attachment sites for the symbionts on the cell envelope of the flagellate host.
      Based on the isolated phylogenetic position and the specific association with the
      surface of Staurojoenina sp., we propose to classify this new taxon of
      Bacteroidales under the provisional name 'Candidatus Vestibaculum illigatum'.

PMID- 15256566
TI  - The nitrogen-fixing gene (nifH) of Rhodopseudomonas palustris: a case of lateral
      gene transfer?
AB  - Nitrogen fixation is catalysed by some photosynthetic bacteria. This paper
      presents a phylogenetic comparison of a nitrogen fixation gene (nifH) with the
      aim of elucidating the processes underlying the evolutionary history of
      Rhodopseudomonas palustris. In the NifH phylogeny, strains of Rps. palustris were
      placed in close association with Rhodobacter spp. and other phototrophic purple
      non-sulfur bacteria belonging to the alpha-Proteobacteria, separated from its
      close relatives Bradyrhizobium japonicum and the phototrophic rhizobia
      (Bradyrhizobium spp. IRBG 2, IRBG 228, IRBG 230 and BTAi 1) as deduced from the
      16S rRNA phylogeny. The close association of the strains of Rps. palustris with
      those of Rhodobacter and Rhodovulum, as well as Rhodospirillum rubrum, was
      supported by the mol% G+C of their nifH gene and by the signature sequences found
      in the sequence alignment. In contrast, comparison of a number of informational
      and operational genes common to Rps. palustris CGA009, B. japonicum USDA 110 and
      Rhodobacter sphaeroides 2.4.1 suggested that the genome of Rps. palustris is more
      related to that of B. japonicum than to the Rba. sphaeroides genome. These
      results strongly suggest that the nifH of Rps. palustris is highly related to
      those of the phototrophic purple non-sulfur bacteria included in this study, and
      might have come from an ancestral gene common to these phototrophic species
      through lateral gene transfer. Although this finding complicates the use of nifH
      to infer the phylogenetic relationships among the phototrophic bacteria in
      molecular diversity studies, it establishes a framework to resolve the origins
      and diversification of nitrogen fixation among the phototrophic bacteria in the
      alpha-Proteobacteria.

PMID- 15256567
TI  - Comparative analysis of eukaryotic-type protein phosphatases in two streptomycete
      genomes.
AB  - Inspection of the genomes of Streptomyces coelicolor A3(2) and Streptomyces
      avermitilis reveals that each contains 55 putative eukaryotic-type protein
      phosphatases (PPs), the largest number ever identified from any single
      prokaryotic organism. Unlike most other prokaryotic genomes that have only one or
      two superfamilies of eukaryotic-type PPs, the streptomycete genomes possess the
      eukaryotic-type PPs that belong to four superfamilies: 2 phosphoprotein
      phosphatases and 2 low-molecular-mass protein tyrosine phosphatases in each
      species, 49 Mg(2+)- or Mn(2+)-dependent protein phosphatases (PPMs) and 2
      conventional protein tyrosine phosphatases (CPTPs) in S. coelicolor A3(2), and 48
      PPMs and 3 CPTPs in S. avermitilis. Sixty-four percent of the PPs found in S.
      coelicolor A3(2) have orthologues in S. avermitilis, indicating that they
      originated from a common ancestor and might be involved in the regulation of more
      conserved metabolic activities. The genes of eukaryotic-type PP unique to each
      surveyed streptomycete genome are mainly located in two arms of the linear
      chromosomes and their evolution might be involved in gene acquisition or
      duplication to adapt to the extremely variable soil environments where these
      organisms live. In addition, 56 % of the PPs from S. coelicolor A3(2) and 65 % of
      the PPs from S. avermitilis possess at least one additional domain having a
      putative biological function. These include the domains involved in the detection
      of redox potential, the binding of cyclic nucleotides, mRNA, DNA and ATP, and the
      catalysis of phosphorylation reactions. Because they contained multiple
      functional domains, most of them were assigned functions other than PPs in
      previous annotations. Although few studies have been conducted on the
      physiological functions of the PPs in streptomycetes, the existence of large
      numbers of putative PPs in these two streptomycete genomes strongly suggests that
      eukaryotic-type PPs play important regulatory roles in primary or secondary
      metabolic pathways. The identification and analysis of such a large number of
      putative eukaryotic-type PPs from S. coelicolor A3(2) and S. avermitilis
      constitute a basis for further exploration of the signal transduction pathways
      mediated by these phosphatases in industrially important strains of
      streptomycetes.

PMID- 15256568
TI  - Enzyme system of Clostridium stercorarium for hydrolysis of arabinoxylan:
      reconstitution of the in vivo system from recombinant enzymes.
AB  - Four extracellular enzymes of the thermophilic bacterium Clostridium stercorarium
      are involved in the depolymerization of de-esterified arabinoxylan: Xyn11A,
      Xyn10C, Bxl3B, and Arf51B. They were identified in a collection of eight clones
      producing enzymes hydrolysing xylan (xynA, xynB, xynC), beta-xyloside (bxlA,
      bxlB, bglZ) and alpha-arabinofuranoside (arfA, arfB). The modular enzymes Xyn11A
      and Xyn10C represent the major xylanases in the culture supernatant of C.
      stercorarium. Both hydrolyse arabinoxylan in an endo-type mode, but differ in the
      pattern of the oligosaccharides produced. Of the glycosidases, Bxl3B degrades
      xylobiose and xylooligosaccharides to xylose, and Arf51B is able to release
      arabinose residues from de-esterified arabinoxylan and from the oligosaccharides
      generated. The other glycosidases either did not attack or only marginally
      attacked these oligosaccharides. Significantly more xylanase and xylosidase
      activity was produced during growth on xylose and xylan. This is believed to be
      the first time that, in a single thermophilic micro-organism, the complete set of
      enzymes (as well as the respective genes) to completely hydrolyse de-esterified
      arabinoxylan to its monomeric sugar constituents, xylose and arabinose, has been
      identified and the enzymes produced in vivo. The active enzyme system was
      reconstituted in vitro from recombinant enzymes.

PMID- 15256569
TI  - Are some putative glycogen accumulating organisms (GAO) in anaerobic : aerobic
      activated sludge systems members of the alpha-Proteobacteria?
AB  - Activated sludge plants designed to remove phosphorus microbiologically often
      perform unreliably. One suggestion is that the polyphosphate-accumulating
      organisms (PAO) are out-competed for substrates by another group of bacteria, the
      glycogen-accumulating organisms (GAO) in the anaerobic zones of these processes.
      This study used fluorescence in situ hybridization (FISH) and denaturing gradient
      gel electrophoresis (DGGE) to analyse the communities from laboratory-scale
      anaerobic : aerobic sequencing batch reactors. Members of the genus Sphingomonas
      in the alpha-Proteobacteria were present in large numbers in communities with
      poor phosphorus removal capacity where the biomass had a high glycogen content.
      Their ability to store poly-beta-hydroxyalkanoates anaerobically, but not
      aerobically, and not accumulate polyphosphate aerobically is consistent with
      these organisms behaving as GAO there. No evidence was found to support an
      important role for the gamma-Proteobacteria as possible GAO in these communities,
      although these bacterial populations have been considered in other studies to act
      as possible competitors for the PAO.

PMID- 15256570
TI  - Genetic analysis of the Bacillus subtilis sigG promoter, which controls the
      sporulation-specific transcription factor sigma G.
AB  - At the onset of sporulation in Bacillus subtilis, an asymmetric cell division
      gives rise to two unequal-sized compartments with distinct developmental fates.
      The smaller compartment, or prespore, becomes the spore, whilst the larger
      compartment, or mother cell, eventually lyses after contributing to spore
      maturation. The fate of each compartment is determined by differential gene
      expression, controlled by the activation of four compartment-specific sigma
      factors. The expression and activity of all four sigma-factors are tightly
      regulated to ensure the correct sequence of morphological events. Prespore
      specific genes are transcribed by two sigma-factors, sigma(F) followed by
      sigma(G). The gene encoding sigma(G) (sigG) is transcribed by sigma(F), but also
      requires the activity of one of the mother-cell-specific sigma-factors, sigma(E),
      for its expression. The minimal promoter required for dependence on sigma(E) was
      found to stretch to just upstream of the -35 site. Analysis of mutant sigG
      promoters generated by site-directed mutagenesis and sigG promoters from other
      species suggests the presence of a binding site for a transcriptional repressor
      within the sigG promoter region. Replacement of the wild-type promoter with
      sigma(E)-independent promoters resulted in impairment of sporulation. These data
      support the idea that sigma(E) activity is required for the transcription of
      sigG.

PMID- 15256571
TI  - Gene array analysis of Yersinia enterocolitica FlhD and FlhC: regulation of
      enzymes affecting synthesis and degradation of carbamoylphosphate.
AB  - This paper focuses on global gene regulation by FlhD/FlhC in enteric bacteria.
      Even though Yersinia enterocolitica FlhD/FlhC can complement an Escherichia coli
      flhDC mutant for motility, it is not known if the Y. enterocolitica FlhD/FlhC
      complex has an effect on metabolism similar to E. coli. To study metabolic gene
      regulation, a partial Yersinia enterocolitica 8081c microarray was constructed
      and the expression patterns of wild-type cells were compared to an flhDC mutant
      strain at 25 and 37 degrees C. The overlap between the E. coli and Y.
      enterocolitica FlhD/FlhC regulated genes was 25 %. Genes that were regulated at
      least fivefold by FlhD/FlhC in Y. enterocolitica are genes encoding urocanate
      hydratase (hutU), imidazolone propionase (hutI), carbamoylphosphate synthetase
      (carAB) and aspartate carbamoyltransferase (pyrBI). These enzymes are part of a
      pathway that is involved in the degradation of L-histidine to L-glutamate and
      eventually leads into purine/pyrimidine biosynthesis via carbamoylphosphate and
      carbamoylaspartate. A number of other genes were regulated at a lower rate. In
      two additional experiments, the expression of wild-type cells grown at 4 or 25
      degrees C was compared to the same strain grown at 37 degrees C. The expression
      of the flagella master operon flhD was not affected by temperature, whereas the
      flagella-specific sigma factor fliA was highly expressed at 25 degrees C and
      reduced at 4 and 37 degrees C. Several other flagella genes, all of which are
      under the control of FliA, exhibited a similar temperature profile. These data
      are consistent with the hypothesis that temperature regulation of flagella genes
      might be mediated by the flagella-specific sigma factor FliA and not the flagella
      master regulator FlhD/FlhC.

PMID- 15256572
TI  - The complex structure of polyhydroxybutyrate (PHB) granules: four orthologous and
      paralogous phasins occur in Ralstonia eutropha.
AB  - Analysis of the genome sequence of the polyhydroxyalkanoate- (PHA) accumulating
      bacterium Ralstonia eutropha strain H16 revealed three homologues (PhaP2, PhaP3
      and PhaP4) of the phasin protein PhaP1. PhaP1 is known to constitute the major
      component of the layer at the surface of poly(3-hydroxybutyrate), poly(3HB),
      granules. PhaP2, PhaP3 and PhaP4 exhibited 42, 49 and 45 % identity or 61, 62 and
      63 % similarity to PhaP1, respectively. The calculated molecular masses of PhaP1,
      PhaP2, PhaP3 and PhaP4 were 20.0, 20.2, 19.6 and 20.2 kDa, respectively. RT-PCR
      analysis showed that phaP2, phaP3 and phaP4 were transcribed under conditions
      permissive for accumulation of poly(3HB). 2D PAGE of the poly(3HB) granule
      proteome and analysis of the detected proteins by MALDI-TOF clearly demonstrated
      that PhaP1, PhaP3 and PhaP4 are bound to the poly(3HB) granules in the cells.
      PhaP3 was expressed at a significantly higher level in PhaP1-negative mutants.
      Occurrence of an unknown protein with an N-terminal amino-acid sequence identical
      to that of PhaP2 in crude cellular extracts of R. eutropha had previously been
      shown by others. Although PhaP2 could not be localized in vivo on poly(3HB)
      granules, in vitro experiments clearly demonstrated binding of PhaP2 to these
      granules. Further analysis of complete or partial genomes of other poly(3HB)
      accumulating bacteria revealed the existence of multiple phasin homologues in
      Ralstonia solanacearum, Burkholderia fungorum and Azotobacter vinelandii. These
      new and unexpected findings should affect our current models of PHA-granule
      structure and may also have a considerable impact on the establishment of
      heterologous production systems for PHAs.

PMID- 15256573
TI  - Relationship between codon biased genes, microarray expression values and
      physiological characteristics of Streptococcus pneumoniae.
AB  - A codon-profile strategy was used to predict gene expression levels in
      Streptococcus pneumoniae. Predicted highly expressed (PHE) genes included those
      encoding glycolytic and fermentative enzymes, sugar-conversion systems and
      carbohydrate-transporters. Additionally, some genes required for infection that
      are involved in oxidative metabolism and hydrogen peroxide production were PHE.
      Low expression values were predicted for genes encoding specific regulatory
      proteins like two-component systems and competence genes. Correspondence analysis
      localized 484 ORFs which shared a distinctive codon profile in the right horn.
      These genes had a mean G+C content (33.4 %) that was lower than the bulk of the
      genome coding sequences (39.7 %), suggesting that many of them were acquired by
      horizontal transfer. Half of these genes (242) were pseudogenes, ORFs shorter
      than 80 codons or without assigned function. The remaining genes included several
      virulence factors, such as capsular genes, iga, lytB, nanB, pspA, choline-binding
      proteins, and functions related to DNA acquisition, such as restriction
      modification systems and comDE. In order to compare predicted translation rate
      with the relative amounts of mRNA for each gene, the codon adaptation index (CAI)
      values were compared with microarray fluorescence intensity values following
      hybridization of labelled RNA from laboratory-grown cultures. High mRNA amounts
      were observed in 32.5 % of PHE genes and in 64 % of the 25 genes with the highest
      CAI values. However, high relative amounts of RNA were also detected in 10.4 % of
      non-PHE genes, such as those encoding fatty acid metabolism enzymes and
      proteases, suggesting that their expression might also be regulated at the level
      of transcription or mRNA stability under the conditions tested. The effects of
      codon bias and mRNA amount on different gene groups in S. pneumoniae are
      discussed.

PMID- 15256574
TI  - alpha-Aminoadipate aminotransferase from an extremely thermophilic bacterium,
      Thermus thermophilus.
AB  - The extremely thermophilic bacterium Thermus thermophilus HB27 synthesizes lysine
      through alpha-aminoadipate (AAA). In this study, a T. thermophilus gene encoding
      the enzyme that catalyses transamination of AAA was cloned as a mammalian
      kynurenine/AAA aminotransferase (Kat2) gene homologue. A T. thermophilus mutant
      with disruption of the Kat2 homologue required a longer lag phase for growth and
      showed slower growth in minimal medium. Furthermore, addition of AAA or lysine
      shortened the lag phase and improved the growth rate. The Kat2 homologue was
      therefore termed lysN. LysN recognizes not only 2-oxoadipate, an intermediate of
      lysine biosynthesis, but also 2-oxoisocaproate, 2-oxoisovalerate and 2-oxo-3
      methylvalerate, intermediates of leucine, valine and isoleucine biosyntheses,
      respectively, along with oxaloacetate, a compound in the TCA cycle, as an amino
      acceptor. These results suggest multiple roles of LysN in several cellular
      metabolic pathways including lysine and branched-chain amino acid biosyntheses.

PMID- 15256575
TI  - FixJ-regulated genes evolved through promoter duplication in Sinorhizobium
      meliloti.
AB  - The FixLJ two-component system of Sinorhizobium meliloti is a global regulator,
      turning on nitrogen-fixation genes in microaerobiosis. Up to now, nifA and fixK
      were the only genes known to be directly regulated by FixJ. We used a genomic
      SELEX approach in order to isolate new FixJ targets in the genome. This led to
      the identification of 22 FixJ binding sites, including the known sites in the
      fixK1 and fixK2 promoters. FixJ binding sites are unevenly distributed among the
      three replicons constituting the S. meliloti genome: a majority are carried
      either by pSymA or by a short chromosomal region of non-chromosomal origin. Thus
      FixJ binding sites appear to be preferentially associated with the pSymA
      replicon, which carries the fixJ gene. Functional analysis of FixJ targets led to
      the discovery of two new FixJ-regulated genes, smc03253 and proB2. This FixJ
      dependent regulation appears to be mediated by a duplication of the whole fixK
      promoter region, including the beginning of the fixK gene. Similar duplications
      were previously reported for the nifH promoter. By systematic comparison of all
      promoter regions we found 17 such duplications throughout the genome, indicating
      that promoter duplication is a common mechanism for the evolution of regulatory
      pathways in S. meliloti.

PMID- 15256576
TI  - Drosophila melanogaster as a model host for Staphylococcus aureus infection.
AB  - Staphylococcus aureus is an important pathogen of humans, causing a range of
      superficial and potentially life-threatening diseases. Infection of the fruit fly
      Drosophila melanogaster with S. aureus results in systemic infection followed by
      death. Screening of defined S. aureus mutants for components important in
      pathogenesis identified perR and pheP, with fly death up to threefold slower
      after infection with the respective mutants compared to the wild-type. Infection
      of D. melanogaster with reporter gene fusion strains demonstrated the in vivo
      expression levels of the accessory gene regulator, agr, alpha-toxin, hla, and a
      manganese transporter, mntA. The use of the green fluorescent protein as a
      reporter under the control of the agr promoter (P3) showed S. aureus microcolony
      formation in vivo. The disease model also allowed the effect of antibiotic
      treatment on the flies to be determined. D. melanogaster is a genetically
      tractable model host for high-throughput analysis of S. aureus virulence
      determinants.

PMID- 15256577
TI  - Positive effects of multiple pch genes on expression of the locus of enterocyte
      effacement genes and adherence of enterohaemorrhagic Escherichia coli O157 : H7
      to HEp-2 cells.
AB  - Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC,
      respectively) genomes contain a pathogenicity island, termed the locus of
      enterocyte effacement (LEE), which encodes genes involved in the formation of
      attaching and effacing lesions on epithelial cells. To elucidate the regulatory
      mechanism of the LEE genes in EHEC, an EHEC O157 genomic library was screened for
      clones which modulated expression of the LEE genes. From more than 5000 clones, a
      DNA fragment was obtained containing a perC homologue as a positive regulator for
      the LEE genes. In EPEC, perC is known to be part of the per operon, along with
      perA and perB, located on the EPEC adherence factor plasmid, which is not found
      in EHEC. However, the complete genome sequence of EHEC O157 Sakai strain reveals
      that there are five perC-like sequences, but no perA and perB, on the chromosome.
      These five perC homologues were characterized, and it was found that three of the
      homologues (renamed perC homologue pchA, pchB and pchC) encoded 104 aa proteins,
      and when expressed on a multicopy plasmid enhanced the expression of LEE genes.
      In contrast, perC homologues encoding proteins of 89 and 90 aa, renamed pchD and
      pchE, respectively, had no significant effect. Deletion mutants of the pch genes
      were constructed, and the effect on the expression of LEE-encoded type III
      effector proteins, such as EspA, B and D, and adhesion phenotype to HEp-2 cells
      was examined. Deletion of pchA or pchB, but not pchC, decreased the expression of
      Esp proteins and adhesion to HEp-2 cells. Such effects were more apparent with
      mutants carrying double deletions of pchA/pchB or pchA/pchC, suggesting that
      pchA/B/C are all necessary for full expression of the LEE genes and adhesion to
      HEp-2 cells. Further study demonstrated that the positive effect of pchA/B/C was
      caused by enhanced transcription of the LEE-encoded regulatory gene, ler.
      Introduction of a multicopy plasmid carrying each pchA/B/C gene significantly
      induced microcolony formation by EHEC O157 on HEp-2 cells. These results suggest
      that the pchABC genes are necessary for full virulence of EHEC O157.

PMID- 15256578
TI  - Active domains of salivary statherin on apatitic surfaces for binding to
      Fusobacterium nucleatum cells.
AB  - Fusobacterium nucleatum can bind to saliva-coated tooth surfaces. However, the
      nature of the domains of salivary protein that interact with F. nucleatum remains
      unclear. The ability of individual proteins in human submandibular-sublingual
      saliva (HSMSL) to bind F. nucleatum cells was examined by dot blot assay;
      statherin displayed the strongest binding activity. Statherin binding sites were
      determined based on binding of (125)I-labelled F. nucleatum to statherin-coated
      hydroxyapatite (sHAP) beads via inhibition assays using synthetic analogous
      peptide fragments of whole statherin. Analogous peptides corresponding to
      residues 19-26 and 32-39 of statherin inhibited binding by 77 % and 68 %,
      respectively. Synthetic peptides were also prepared by serial deletions of
      individual residues from N- and C-termini of the peptides GPYQPVPE (aa 19-26) and
      QPYQPQYQ (aa 32-39). The inhibitory effects of peptides YQPVPE (aa 21-26) and
      PYQPQYQ (aa 33-39) were very similar to those of GPYQPVPE and QPYQPQYQ,
      respectively. However, additional deletion of residues resulted in significant
      reduction of the inhibitory effect. Alanine-scan analysis of YQPVPE revealed that
      all tested peptides retained inhibitory activity; only YAPVPE exhibited
      significantly decreased inhibitory activity. These findings suggest that YQPVPE
      and PYQPQYQ may represent the minimal active segments of statherin for binding to
      F. nucleatum; moreover, Gln may be a key amino acid in the active segment.

PMID- 15256579
TI  - Biochemical characterization of different genotypes of Paenibacillus larvae
      subsp. larvae, a honey bee bacterial pathogen.
AB  - Paenibacillus larvae subsp. larvae (P. l. larvae) is the aetiological agent of
      American foulbrood (AFB), the most virulent bacterial disease of honey bee brood
      worldwide. In many countries AFB is a notifiable disease since it is highly
      contagious, in most cases incurable and able to kill affected colonies.
      Genotyping of field isolates of P. l. larvae revealed at least four genotypes
      (AB, Ab, ab and alpha B) present in Germany which are genotypically different
      from the reference strain DSM 7030. Therefore, based on these data, five
      different genotypes of P. l. larvae are now identified with genotype AB standing
      out with a characteristic brown-orange and circled two-coloured colony
      morphology. Analysing the metabolic profiles of three German genotypes (AB, Ab
      and ab) as well as of the reference strain using the Biolog system, a
      characteristic biochemical fingerprint could be obtained for each strain. Cluster
      analysis showed that while genotypes Ab, ab and the reference strain DSM 7030 are
      rather similar, genotype AB is clearly different from the others. Analysis of all
      isolates for plasmid DNA revealed two different plasmids present only in isolates
      belonging to genotype AB. Therefore, genotype AB is remarkable in all aspects
      analysed so far. Future analysis will show whether or not these differences will
      expand to differences in virulence.

PMID- 15256580
TI  - Adherence of Actinobacillus pleuropneumoniae to swine-lung collagen.
AB  - Actinobacillus pleuropneumoniae serotype 1 adhered to immobilized swine-lung
      collagen. Bacteria bound to collagen type I, III, IV and V. At 5 min incubation,
      30 % of bacteria adhered to collagen, reaching saturation in around 90 min.
      Treatment of bacteria with divalent-metal chelators diminished their attachment
      to collagen, and Ca(2+) but not Mg(2+) increased it, suggesting Ca(2+) dependence
      for adherence. Proteolytic enzymes drastically reduced bacterial adherence to
      collagen, showing that binding involved bacterial surface proteins. Porcine
      fibrinogen, haemoglobin and gelatin partially reduced collagen adhesion. A 60 kDa
      outer-membrane protein of A. pleuropneumoniae recognized the swine collagens by
      overlay. This membrane protein was apparently involved in adhesion to collagen
      and fibrinogen, but not to fibronectin and laminin. Antibodies against the 60 kDa
      protein inhibited the adhesion to collagen by 70 %, whereas pig convalescent
      phase antibodies inhibited it by only 40 %. Serotypes 1 and 7 were the most
      adherent to pig collagen (taken as 100 %); serotypes 6 and 11 were the lowest
      (approximately 50 %), and neither showed the 60 kDa adhesin to biotinylated
      collagens. By negative staining, cells were observed initially to associate with
      collagen fibres in a polar manner, and the adhesin was detected on the bacterial
      surface. The results suggest that swine-lung collagen is an important target for
      A. pleuropneumoniae colonization and spreading, and that the attachment to this
      protein could play a relevant role in pathogenesis.

PMID- 15256581
TI  - Genetic analysis of Treponema denticola ATCC 35405 biofilm formation.
AB  - Treponema denticola is a major aetiological organism implicated in periodontal
      disease. The interaction of T. denticola with other oral bacteria, in particular
      Porphyromonas gingivalis, in biofilm formation is thought to be an important step
      in the onset of periodontal disease. The interaction between T. denticola and P.
      gingivalis has been examined using a panel of T. denticola mutants and their
      effects on mixed biofilm formation tested in a static biofilm model. T. denticola
      ATCC 35405 did not form detectable biofilms on various inert surfaces. However,
      the spirochaete was demonstrated to form a biofilm with preattached P. gingivalis
      381. T. denticola cfpA, which lacks the cytoplasmic filament, was unable to
      produce a mixed biofilm with P. gingivalis. A T. denticola flgE mutant which
      lacks the flagella hook protein and is therefore non-motile displayed a reduced,
      but readily detectable, ability to form a mixed biofilm as did the T. denticola
      mutant which does not possess the major outer sheath protein (Msp). The T.
      denticola lrrA mutant was only moderately defective in forming mixed biofilms
      with P. gingivalis. However, the T. denticola methyl-accepting chemotaxis protein
      (DmcA) did not appear to play a major role in mixed biofilm formation. In
      contrast, T. denticola lacking the PrtP protein for prolyl-phenylalanine-specific
      protease, showed an increased ability to form mixed biofilms and a prolonged
      viability in the biofilm.

PMID- 15256582
TI  - rexAB mutants in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a human pathogen that is naturally transformable. In
      this study a major component of the homologous recombination pathway, the RexAB
      exonuclease/helicase, was characterized. rexA and rexB insertional mutants were
      constructed using mariner mutagenesis and found to have identical phenotypes.
      Both rexAB mutants displayed poor cell viability, reduced double-strand
      exonuclease activity, UV sensitivity and a reduced level of gene conversion
      compared to the wild-type strain. No effect was observed on plasmid and
      chromosomal transformation efficiencies. These results indicate that in S.
      pneumoniae, RexAB is required for DNA repair, but not for chromosomal
      transformation and plasmid establishment.

PMID- 15256583
TI  - ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin;
      functional comparisons between Als3p and Als1p.
AB  - The ALS (agglutinin-like sequence) gene family of Candida albicans encodes eight
      cell-surface glycoproteins, some of which are involved in adherence to host
      surfaces. A mutational analysis of each ALS gene is currently being performed to
      deduce the functions of the encoded proteins and to better understand the role of
      these proteins in C. albicans biology and pathogenesis. This paper describes
      construction of an als3/als3 mutant and comparison of its phenotype to an
      als1/als1 strain. Efforts to disrupt ALS3 indicated that the gene could be
      deleted in two transformation steps, suggesting that the gene is encoded by a
      single locus and that the ALS3-like locus, ALS8, does not exist. Strains lacking
      ALS3 or ALS1 did not exhibit a defect in germ tube formation when grown in RPMI
      1640 medium, but the als1/als1 mutant formed significantly fewer germ tubes in
      Lee medium. Analysis of ALS3 and ALS1 promoter activity using green fluorescent
      protein (GFP) reporter strains and flow cytometry showed that when cells are
      placed into medium that promotes germ tube formation, ALS1 is transcribed prior
      to ALS3. Comparison of the mutant strains in adhesion assays showed that the
      als3/als3 strain was defective in adhesion to both human umbilical vein
      endothelial cells (HUVEC) and buccal epithelial cells (BEC), but not to
      fibronectin-coated plastic plates. In contrast, the als1/als1 strain showed
      decreased adherence to HUVEC, but adherence to BEC and fibronectin were the same
      as wild-type controls. Inoculation of the buccal reconstituted human epithelium
      (RHE) model of oral candidiasis with the mutant strains showed nearly a total
      lack of adhesion and epithelial destruction by the als3/als3 mutant while the
      als1/als1 strain showed only a slightly reduced degree of epithelial destruction
      compared to the wild-type control. Adhesion data presented here suggest that, in
      the assays performed, loss of Als3p affects C. albicans adhesion more than loss
      of Als1p. Collectively, these results demonstrate functional similarities and
      differences between Als1p and Als3p, and suggest the potential for more complex
      interrelationships between the ALS genes and their encoded proteins.

PMID- 15256584
TI  - Ffz1, a new transporter specific for fructose from Zygosaccharomyces bailii.
AB  - The basis of fructophily in the yeast Zygosaccharomyces bailii has been shown to
      reside in the performance of transport systems for hexoses. In this study, a gene
      encoding a fructose-specific transporter was characterized. The strategy involved
      the functional complementation of a Saccharomyces cerevisiae strain that does not
      take up hexoses (hxt-null strain). This strain was transformed with a genomic
      library of Z. bailii. One transformant capable of growing on fructose, but not on
      glucose, was obtained. This transformant did not transport d-[(14)C]glucose, and
      the kinetic parameters for d-[(14)C]fructose were V(max)=3.3 mmol h(-1) g(-1) and
      K(m)=80.4 mM. As in the original strain of Z. bailii, fructose uptake was not
      inhibited by the presence of other hexoses or uranyl. The plasmid responsible for
      the observed phenotype was found to carry an ORF encoding a 616 amino acid
      protein with the characteristics of a membrane transporter, which was designated
      FFZ1 (fructose facilitator Zygosaccharomyces). The impairment in function
      observed in an S. cerevisiae transformant expressing a truncated Ffz1 protein
      lacking 67 amino acids at the C-terminus suggests an important role for this
      terminal part in the proper structure of the transporter.

PMID- 15256585
TI  - Anaerobic growth of the haloalkaliphilic denitrifying sulfur-oxidizing bacterium
      Thialkalivibrio thiocyanodenitrificans sp. nov. with thiocyanate.
AB  - Two strains of obligate chemolithoautotrophic sulfur-oxidizing bacteria were
      isolated from soda-lake sediments by enrichment culture with thiocyanate and
      nitrate at pH 9.9. The isolates were capable of growth with thiocyanate or
      thiosulfate as electron donor, either aerobically or anaerobically, and with
      nitrate or nitrite as electron acceptor. Cyanate was identified as an
      intermediate of thiocyanate oxidation, while sulfate, ammonia and dinitrogen gas
      were the final products. The anaerobic growth on thiocyanate plus nitrate was
      much slower (mu(max)=0.006 h(-1)) than on thiosulfate plus nitrate (mu(max)=0.02
      h(-1)), while growth yields were similar (4.8 and 5.1 g protein mol(-1),
      respectively). On the basis of their phenotypic and genetic properties, strains
      ARhD 1(T) and ARhD 2 are described as a novel species of the genus
      Thialkalivibrio, with the highest similarity to Thialkalivibrio denitrificans.
      The name Thialkalivibrio thiocyanodenitrificans sp. nov. is proposed for this
      novel species.

PMID- 15256586
TI  - The putative permease PhlE of Pseudomonas fluorescens F113 has a role in 2,4
      diacetylphloroglucinol resistance and in general stress tolerance.
AB  - 2,4-Diacetylphloroglucinol (PHL) is the primary determinant of the biological
      control activity of Pseudomonas fluorescens F113. The operon phlACBD encodes
      enzymes responsible for PHL biosynthesis from intermediate metabolites. The phlE
      gene, which is located downstream of the phlACBD operon, encodes a putative
      permease suggested to be a member of the major facilitator superfamily with 12
      transmembrane segments. PhlE has been suggested to function in PHL export. Here
      the sequencing of the phlE gene from P. fluorescens F113 and the construction of
      a phlE null mutant, F113-D3, is reported. It is shown that F113-D3 produced less
      PHL than F113. The ratio of cell-associated to free PHL was not significantly
      different between the strains, suggesting the existence of alternative
      transporters for PHL. The phlE mutant was, however, significantly more sensitive
      to high concentrations of added PHL, implicating PhlE in PHL resistance.
      Furthermore, the phlE mutant was more susceptible to osmotic, oxidative and heat
      shock stresses. Osmotic stress induced rapid degradation of free PHL by the
      bacteria. Based on these results, we propose that the role of phlE in general
      stress tolerance is to export toxic intermediates of PHL degradation from the
      cells.

PMID- 15256587
TI  - A multisubunit membrane-bound [NiFe] hydrogenase and an NADH-dependent Fe-only
      hydrogenase in the fermenting bacterium Thermoanaerobacter tengcongensis.
AB  - Thermoanaerobacter tengcongensis is a thermophilic Gram-positive bacterium able
      to dispose of the reducing equivalents generated during the fermentation of
      glucose to acetate and CO(2) by reducing H(+) to H(2). A unique combination of
      hydrogenases, a ferredoxin-dependent [NiFe] hydrogenase and an NADH-dependent Fe
      only hydrogenase, were found to be responsible for H(2) formation in this
      organism. Both enzymes were purified and characterized. The tightly membrane
      bound [NiFe] hydrogenase belongs to a small group of complex-I-related [NiFe]
      hydrogenases and has highest sequence similarity to energy-converting [NiFe]
      hydrogenase (Ech) from Methanosarcina barkeri. A ferredoxin isolated from Ta.
      tengcongensis was identified as the physiological substrate of this enzyme. The
      heterotetrameric Fe-only hydrogenase was isolated from the soluble fraction. It
      contained FMN and multiple iron-sulfur clusters, and exhibited a typical H
      cluster EPR signal after autooxidation. Sequence analysis predicted and kinetic
      studies confirmed that the enzyme is an NAD(H)-dependent Fe-only hydrogenase.
      When H(2) was allowed to accumulate in the culture, the fermentation was
      partially shifted to ethanol production. In cells grown at high hydrogen partial
      pressure [p(H(2))] the NADH-dependent hydrogenase activity was fourfold lower
      than in cells grown at low p(H(2)), whereas aldehyde dehydrogenase and alcohol
      dehydrogenase activities were higher in cells grown at elevated p(H(2)). These
      results indicate a regulation in response to the p(H(2)).

PMID- 15256588
TI  - Extended phenotype of an mreB-like mutant in Azospirillum brasilense.
AB  - Tn5 mutagenesis was used to generate an Azospirillum brasilense SPF94 mutant.
      Genetic analysis of this mutant revealed that a homologue of the mreB gene, which
      controls cell shape in Bacillus subtilis and Escherichia coli, was inactivated.
      The cell-surface properties of the mutant were different from those of the
      parental strain. The mutant colonies were highly fluorescent when grown on plates
      containing Calcofluor White. Light and electron microscopy revealed that the
      mutant cells were round and had thicker capsules than the spiral parental strain.
      The mutants contained up to ten times more capsule protein than the parental
      strain, but lacked a 40 kDa protein that is abundant in the parental strain. The
      phenotype of the isolated mutant resembled that of the cyst-like differentiated
      forms of Azospirillum, suggesting that the mreB homologue could be involved in
      differentiation.

PMID- 15256589
TI  - An aspartic proteinase gene family in the filamentous fungus Botrytis cinerea
      contains members with novel features.
AB  - Botrytis cinerea, an important fungal plant pathogen, secretes aspartic
      proteinase (AP) activity in axenic cultures. No cysteine, serine or
      metalloproteinase activity could be detected. Proteinase activity was higher in
      culture medium containing BSA or wheat germ extract, as compared to minimal
      medium. A proportion of the enzyme activity remained in the extracellular glucan
      sheath. AP was also the only type of proteinase activity in fluid obtained from
      B. cinerea-infected tissue of apple, pepper, tomato and zucchini. Five B. cinerea
      genes encoding an AP were cloned and denoted Bcap1-5. Features of the encoded
      proteins are discussed. BcAP1, especially, has novel characteristics. A
      phylogenetic analysis was performed comprising sequences originating from
      different kingdoms. BcAP1 and BcAP5 did not cluster in a bootstrap-supported
      clade. BcAP2 clusters with vacuolar APs. BcAP3 and BcAP4 cluster with secreted
      APs in a clade that also contains glycosylphosphatidylinositol-anchored
      proteinases from Saccharomyces cerevisiae and Candida albicans. All five Bcap
      genes are expressed in liquid cultures. Transcript levels of Bcap1, Bcap2, Bcap3
      and Bcap4 are subject to glucose and peptone repression. Transcripts from all
      five Bcap genes were detected in infected plant tissue, indicating that at least
      part of the AP activity in planta originates from the pathogen.

PMID- 15256590
TI  - Mitogen-activated protein kinase pathways defend against bacterial pore-forming
      toxins.
AB  - Cytolytic pore-forming toxins are important for the virulence of many disease
      causing bacteria. How target cells molecularly respond to these toxins and
      whether or not they can mount a defense are poorly understood. By using
      microarrays, we demonstrate that the nematode Caenorhabditis elegans responds
      robustly to Cry5B, a member of the pore-forming Crystal toxin family made by
      Bacillus thuringiensis. This genomic response is distinct from that seen with a
      different stressor, the heavy metal cadmium. A p38 mitogen-activated protein
      kinase (MAPK) kinase and a c-Jun N-terminal-like MAPK are both transcriptionally
      up-regulated by Cry5B. Moreover, both MAPK pathways are functionally important
      because elimination of either leads to animals that are (i) hypersensitive to a
      low, chronic dose of toxin and (ii) hypersensitive to a high, brief dose of toxin
      such that the animal might naturally encounter in the wild. These results extend
      to mammalian cells because inhibition of p38 results in the hypersensitivity of
      baby hamster kidney cells to aerolysin, a pore-forming toxin that targets humans.
      Furthermore, we identify two downstream transcriptional targets of the p38 MAPK
      pathway, ttm-1 and ttm-2, that are required for defense against Cry5B. Our data
      demonstrate that cells defend against pore-forming toxins by means of conserved
      MAPK pathways.

PMID- 15256591
TI  - Identification of 315 genes essential for early zebrafish development.
AB  - We completed a large insertional mutagenesis screen in zebrafish to identify
      genes essential for embryonic and early larval development. We isolated 525
      mutants, representing lesions in approximately 390 different genes, and we cloned
      the majority of these. Here we describe 315 mutants and the corresponding genes.
      Our data suggest that there are roughly 1,400 embryonic-essential genes in the
      fish. Thus, we have mutations in approximately 25% of these genes and have cloned
      approximately 22% of them. Re-screens of our collection to identify mutants with
      specific developmental defects suggest that approximately 50 genes are essential
      for the development of some individual organs or cell types. Seventy-two percent
      of the embryonic-essential fish genes have homologues in yeast, 93% have
      homologues in invertebrates (fly or worm), and 99% have homologues in human.
      Yeast and worm orthologues of genes that are essential for early zebrafish
      development have a strong tendency to be essential for viability in yeast and for
      embryonic development in the worm. Thus, the trait of being a genetically
      essential gene is conserved in evolution. This mutant collection should be a
      valuable resource for diverse studies of cell and developmental biology.

PMID- 15256592
TI  - MRI detection of single particles for cellular imaging.
AB  - There is rapid growth in the use of MRI for molecular and cellular imaging. Much
      of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran
      coated iron oxide particles. Typically, millions of dextran-coated ultrasmall
      iron oxide particles must be loaded into cells for efficient detection. Here we
      show that single, micrometer-sized iron oxide particles (MPIOs) can be detected
      by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos.
      Experiments studying effects of MRI resolution and particle size from 0.76 to
      1.63 microm indicated that T(2)* effects can be readily detected from single
      MPIOs at 50-microm resolution and significant signal effects could be detected at
      resolutions as low as 200 microm. Cultured cells were labeled with fluorescent
      MPIOs such that single particles were present in individual cells. These single
      particles in single cells could be detected both by MRI and fluorescence
      microscopy. Finally, single particles injected into single-cell-stage mouse
      embryos could be detected at embryonic day 11.5, demonstrating that even after
      many cell divisions, daughter cells still carry individual particles. These
      results demonstrate that MRI can detect single particles and indicate that single
      particle detection will be useful for cellular imaging.

PMID- 15256593
TI  - Innervation of ectopic endometrium in a rat model of endometriosis.
AB  - Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial
      tissue occur outside the uterus. Its symptoms include reduced fertility and
      severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke
      symptoms are poorly understood. One factor not yet considered is that the ectopic
      growths develop their own innervation. Here, we tested the hypothesis that the
      growths develop both an autonomic and a sensory innervation. We used a rat model
      of surgically induced ENDO whose growths mimic those in women. Furthermore,
      similar to women with ENDO, such rats exhibit reduced fertility and increased
      pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric
      cascade arteries, small pieces of uterus that formed vascularized cysts. The
      cysts and healthy uterus were harvested from proestrous rats and immunostained
      using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene
      related peptide (CGRP) (sensory C and A delta fibers), substance P (SP) (sensory
      C and A delta fibers) and vesicular monoamine transporter (sympathetic fibers).
      Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained
      neurites accompanying blood vessels and extending into nearby luminal epithelial
      layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites
      also were observed, with CGRP and SP neurites extending the furthest into the
      cyst lining. These results demonstrate that ectopic endometrial growths develop
      an autonomic and sensory innervation. This innervation could contribute not only
      to symptoms associated with ENDO but also to maintenance of the ectopic growths.

PMID- 15256594
TI  - Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress
      resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase.
AB  - The p38 and JNK classes of mitogen-activated protein kinases (MAPKs) have
      evolutionarily conserved roles in the control of cellular responses to microbial
      and abiotic stresses. The mechanisms by which crosstalk between distinct p38 and
      c-Jun N-terminal kinase (JNK) MAPK pathways occurs with resultant integration of
      signaling information have been difficult to establish, particularly in the
      context of whole organism physiology. In Caenorhabditis elegans a PMK-1 p38 MAPK
      pathway is required for resistance to bacterial infection, and a KGB-1 JNK-like
      MAPK pathway has recently been shown to mediate resistance to heavy metal stress.
      Here, we show that two components of the KGB-1 pathway, MEK-1 MAPK kinase
      (MAPKK), a homolog of mammalian MKK7, and VHP-1 MAPK phosphatase (MKP), a homolog
      of mammalian MKP7, also regulate pathogen resistance through the modulation of
      PMK-1 activity. The regulation of p38 and JNK-like MAPK pathways mediating
      immunity and heavy metal stress by common MAPKK and MKP signaling components
      suggests pivotal roles for MEK-1 and VHP-1 in the integration of diverse stress
      signals contributing to pathogen resistance in C. elegans. In addition, these
      data point to mechanisms in multicellular organisms by which signals transduced
      by distinct MAPK pathways may be subject to physiological integration at the
      level of regulation of MAPK activity by MAPKKs and MKPs.

PMID- 15256595
TI  - Structure of the C-terminal domain of the clock protein KaiA in complex with a
      KaiC-derived peptide: implications for KaiC regulation.
AB  - Circadian clocks are widespread endogenous mechanisms that control the temporal
      pattern of diverse biological processes, including gene transcription. KaiA is
      the positive element of the cyanobacterial clock because KaiA overexpression
      elevates transcription levels of clock components. Recently, we showed that the
      structure of KaiA is that of a domain-swapped homodimer. The N-terminal domain is
      a pseudo-receiver; thus, it is likely to be involved in signal transduction in
      the clock-resetting pathway. The C-terminal domain of KaiA is structurally novel
      and enhances the KaiC autokinase activity directly. Here, we report the NMR
      structure of the C-terminal domain of KaiA (ThKaiA180C) in complex with a KaiC
      derived peptide from the cyanobacterium Thermosynechococcus elongatus BP-1. The
      protein-peptide interface is revealed to be different from a model that was
      proposed earlier, is stabilized by a combination of hydrophobic and electrostatic
      interactions, and includes many residues known to produce a circadian-period
      phenotype upon substitution. Although the structure of the monomeric subunit of
      ThKaiA180C is largely unchanged upon peptide binding, the intersubunit
      dimerization angle changes. It is proposed that modulation of the C-terminal KaiA
      domain dimerization angle regulates KaiA-KaiC interactions.

PMID- 15256596
TI  - Design of a directed molecular network.
AB  - An ability to rationally design complex networks from the bottom up can offer
      valuable quantitative model systems for use in gaining a deeper appreciation for
      the principles governing the self-organization and functional characteristics of
      complex systems. We report herein the de novo design, graph prediction,
      experimental analysis, and characterization of simple self-organized, nonlinear
      molecular networks. Our approach makes use of the sequence-dependent auto- and
      cross-catalytic functional characteristics of template-directed peptide fragment
      condensation reactions in neutral aqueous solutions. Starting with an array of 81
      sequence similar 32-residue coiled-coil peptides, we estimated the relative
      stability difference between all plausible A(2)B-type coiled-coil ensembles and
      used this information to predict the auto- and cross-catalysis pathways and the
      resulting plausible network motif and connectivities. Similar to most complex
      systems, the generated graph displays clustered nodes with an overall
      hierarchical architecture. To test the validity of the design principles used,
      nine nodes composing a main segment of the graph were experimentally analyzed for
      their capacity in establishing the predicted network connectivity. The resulting
      self-organized chemical network is shown to display 25 directed edges in good
      agreement with the graph analysis estimations. Moreover, we show that by varying
      the system parameters (presence or absence of certain substrates or templates),
      its operating network motif can be altered, even to the extremes of turning
      pathways on or off. We suggest that this approach can be expanded for the
      construction of large-scale networks, offering a means to study and to understand
      better the emergent, collective behaviors of networks.

PMID- 15256597
TI  - Variable var transition rates underlie antigenic variation in malaria.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is expressed on the
      surface of infected erythrocytes where it plays a central role in both infected
      erythrocytes cytoadhesion and immune evasion. Switches in clonal expression of
      PfEMP1 result in antigenic variation that facilitates long-term chronic infection
      of the host. The var gene family encodes PfEMP1 variants, with transcriptional
      switching between different var variants providing the molecular basis for
      antigenic variation. Despite the importance of var transcriptional switching in
      the evasion of the immune response, little is known about the way in which this
      process is regulated. Here we report the measurement of transition on and off
      rates for a series of var gene variants. We find (i) that on and off rates for a
      given variant are dissimilar, (ii) that these rates vary dramatically among
      different variants, and (iii) that in isogenic clones expressing the same var
      gene, both on and off rates are constant and appear to be an intrinsic property
      of that particular gene. These data would suggest that the information that
      determines the probability of the activation or silencing of var genes is present
      in their surrounding DNA. Furthermore, some transitions appear to be disallowed
      depending on the recent variant antigen expression history of the parasite clone.
      These findings have important implications for both the underlying molecular
      mechanisms of antigenic variation and the processes that promote chronicity of
      infection in vivo.

PMID- 15256598
TI  - A force-dependent switch reverses type IV pilus retraction.
AB  - Type IV pilus dynamics is important for virulence, motility, and DNA transfer in
      a wide variety of prokaryotes. The type IV pilus system constitutes a very robust
      and powerful molecular machine that transports pilus polymers as well as DNA
      through the bacterial cell envelope. In Neisseria gonorrhoeae, pilus retraction
      is a highly irreversible process that depends on PilT, an AAA ATPase family
      member. However, when levels of PilT are reduced, the application of high
      external forces (F = 110 +/- 10 pN) induces processive pilus elongation. At
      forces of >50 pN, single pili elongate at a rate of v = 350 +/- 50 nm/s. For
      forces of <50 pN, elongation velocity depends strongly on force and relaxation
      causes immediate retraction. Both pilus retraction and force-induced elongation
      can be modeled by chemical kinetics with same step length for the rate-limiting
      translocation step. The model implies that a force-dependent molecular switch can
      induce pilus elongation by reversing the retraction mechanism.

PMID- 15256599
TI  - A large conformational change of the translocation ATPase SecA.
AB  - The ATPase SecA mediates the posttranslational translocation of a wide range of
      polypeptide substrates through the SecY channel in the cytoplasmic membrane of
      bacteria. We have determined the crystal structure of a monomeric form of
      Bacillus subtilis SecA at a 2.2-A resolution. A comparison with the previously
      determined structures of SecA reveals a nucleotide-independent, large
      conformational change that opens a deep groove similar to that in other proteins
      that interact with diverse polypeptides. We propose that the open form of SecA
      represents an activated state.

PMID- 15256600
TI  - A point mutation in the regulatory light chain reduces the step size of skeletal
      muscle myosin.
AB  - Current evidence favors the theory that, when the globular motor domain of myosin
      attaches to actin, the light chain binding domain or "lever arm" rotates, and
      thereby generates movement of actin filaments. Myosin is uniquely designed for
      such a role in that a long alpha-helix (approximately 9 nm) extending from the C
      terminus of the catalytic core is stabilized by two calmodulin-like molecules,
      the regulatory light chain (RLC) and the essential light chain (ELC). Here, we
      introduce a single-point mutation into the skeletal myosin RLC, which results in
      a large (approximately 50%) reduction in actin filament velocity (V(actin))
      without any loss in actin-activated MgATPase activity. Single-molecule analysis
      of myosin by optical trapping showed a comparable 2-fold reduction in unitary
      displacement or step size (d), without a significant change in the duration of
      the strongly attached state (tau(on)) after the power stroke. Assuming that
      V(actin) approximately d/tau(on), we can account for the change in velocity
      primarily by a change in the step size of the lever arm without incurring any
      change in the kinetic properties of the mutant myosin. These results suggest that
      a principal role for the many light chain isoforms in the myosin II class may be
      to modulate the flexural rigidity of the light chain binding domain to maximize
      tension development and movement during muscle contraction.

PMID- 15256601
TI  - Transfer of photosynthesis genes to and from Prochlorococcus viruses.
AB  - Comparative genomics gives us a new window into phage-host interactions and their
      evolutionary implications. Here we report the presence of genes central to
      oxygenic photosynthesis in the genomes of three phages from two viral families
      (Myoviridae and Podoviridae) that infect the marine cyanobacterium
      Prochlorococcus. The genes that encode the photosystem II core reaction center
      protein D1 (psbA), and a high-light-inducible protein (HLIP) (hli) are present in
      all three genomes. Both myoviruses contain additional hli gene types, and one of
      them encodes the second photosystem II core reaction center protein D2 (psbD),
      whereas the other encodes the photosynthetic electron transport proteins
      plastocyanin (petE) and ferredoxin (petF). These uninterrupted, full-length genes
      are conserved in their amino acid sequence, suggesting that they encode
      functional proteins that may help maintain photosynthetic activity during
      infection. Phylogenetic analyses show that phage D1, D2, and HLIP proteins
      cluster with those from Prochlorococcus, indicating that they are of
      cyanobacterial origin. Their distribution among several Prochlorococcus clades
      further suggests that the genes encoding these proteins were transferred from
      host to phage multiple times. Phage HLIPs cluster with multicopy types found
      exclusively in Prochlorocococus, suggesting that phage may be mediating the
      expansion of the hli gene family by transferring these genes back to their hosts
      after a period of evolution in the phage. These gene transfers are likely to play
      a role in the fitness landscape of hosts and phages in the surface oceans.

PMID- 15256602
TI  - Modeling a synthetic multicellular clock: repressilators coupled by quorum
      sensing.
AB  - Diverse biochemical rhythms are generated by thousands of cellular oscillators
      that somehow manage to operate synchronously. In fields ranging from circadian
      biology to endocrinology, it remains an exciting challenge to understand how
      collective rhythms emerge in multicellular structures. Using mathematical and
      computational modeling, we study the effect of coupling through intercell
      signaling in a population of Escherichia coli cells expressing a synthetic
      biological clock. Our results predict that a diverse and noisy community of such
      genetic oscillators interacting through a quorum-sensing mechanism should self
      synchronize in a robust way, leading to a substantially improved global
      rhythmicity in the system. As such, the particular system of coupled genetic
      oscillators considered here might be a good candidate to provide the first
      quantitative example of a synchronization transition in a population of
      biological oscillators.

PMID- 15256604
TI  - Quantification of walking mobility in neurological disorders.

PMID- 15256603
TI  - The evolution of reproductive restraint through social communication.
AB  - The evolution of altruistic behavior through group selection is generally viewed
      as possible in theory but unlikely in reality, because individual selection
      favoring selfish strategies should act more rapidly than group selection favoring
      cooperation. Here we demonstrate the evolution of altruism, in the form of
      conditional reproductive restraint based on an explicitly social mechanism,
      modulated by intrapopulation communication comprising signal and evolved
      response, in a spatially distributed predatory/parasitic/pathogenic model system.
      The predatory species consistently comes to exploit a signal implying
      overcrowding, individuals constraining their reproduction in response, with a
      corresponding increase in equilibrium reproduction rate in the absence of signal.
      This signaled restraint arises in a robust way for a range of model spatial
      systems; it outcompetes non-signal-based restraint and is not vulnerable to
      subversion by noncooperating variants. In these systems, communication is used to
      evaluate population density and regulate reproduction accordingly, consistent
      with central ideas of Wynne-Edwards [Wynne-Edwards, V. C. (1962) Animal
      Dispersion in Relation to Social Behavior (Hafner, New York)], whose claims about
      the evolutionary importance of group selection helped ignite decades of
      controversy. This quantitative simulation model shows how the key evolutionary
      transition from solitary living to sociality can occur. The process described
      here of cooperation evolving through communication may also help to explain other
      major evolutionary transitions such as intercellular communication leading to
      multicellular organisms.

PMID- 15256605
TI  - Impacted cerumen: composition, production, epidemiology and management.
AB  - In the UK, some 2.3 million people suffer cerumen ('ear wax') problems serious
      enough to warrant management, with approximately 4 million ears syringed
      annually. Impacted cerumen is a major cause of primary care consultation, and a
      common comorbidity in ENT patients, the elderly, infirm and people with mental
      retardation. Despite this, the physiology, clinical significance and management
      implications of excessive and impacted cerumen remain poorly characterized. There
      are no well-designed, large, placebo-controlled, double-blind studies comparing
      treatments, and accordingly, the evidence surrounding the management of impacted
      cerumen is inconsistent, allowing few conclusions. The causes and management of
      impacted cerumen require further investigation. Physicians are supposed to follow
      the edicts and principles of evidence-based medicine and clinical governance.
      Currently, in patients with impacted cerumen, the lack of evidence makes this
      impossible.

PMID- 15256606
TI  - Domestic risk factors for wheeze in urban and rural Ethiopian children.
AB  - BACKGROUND: To identify which environmental exposures underpin the emergence of
      asthma epidemics, we need to study epidemics as they appear, as is now happening
      in the Jimma region of Ethiopia. We have previously studied risk factors for
      asthma in adults in Jimma and have now completed a survey of young children. AIM:
      To establish the prevalence of asthma in urban and rural children in Jimma, and
      to identify locally important risk factors. DESIGN: Cross-sectional survey.
      METHODS: All children aged 1-5 years living in Jimma town and three surrounding
      rural regions were identified. Data were collected using an interviewer-led
      questionnaire, and consenting children had skin prick tests to house dust mite
      and cockroach. RESULTS: We surveyed 7155 children, of whom 3623 (51%) were female
      and 4285 (60%) lived in the urban area. The prevalence of wheeze in the last year
      was 3.4%, and was lower in the rural area (OR 0.47; 95%CI 0.34-0.66). In the
      urban area, the main risk factors for wheeze were a longer duration of
      breastfeeding, use of kerosene, and environmental tobacco smoke, while living
      with animals was protective. In rural children, the main risk factors were a
      positive skin prick test and living with animals. DISCUSSION: The prevalence of
      wheeze in children in the Jimma region is low, particularly in rural children. In
      addition to having an impact on disease prevalence, place of residence also
      appears to modify the impact of environmental risk factors for wheeze.

PMID- 15256607
TI  - Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia.
AB  - BACKGROUND: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with
      hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by
      multiple organ involvement. The prevalence of thyroid disorders in MC has not yet
      been studied. AIM: To investigate the prevalence and clinical features of thyroid
      involvement in patients with HCV-associated MC (HCV + MC). DESIGN: Case-control
      study. METHODS: HCV + MC patients (n = 93, 17 men and 76 women, mean +/- SD age
      63 +/- 10 years, mean disease duration 14 +/- 7 years) consecutively referred to
      the Rheumatology Unit were matched by sex and age (+/- 2 years) to (i) 93
      patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV
      negative) controls from the local population. Measurements included prevalence of
      hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid
      cancer. RESULTS: By McNemar's chi(2) test, the following thyroid abnormalities
      were significantly more frequent in HCV + MC patients than in HCV-negative
      controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p =
      0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p =
      0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity
      (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in
      HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035). DISCUSSION: The
      prevalence of thyroid disorders is increased in patients with HCV-related mixed
      cryoglobulinaemia. We suggest careful monitoring of thyroid function in these
      patients.

PMID- 15256608
TI  - Acute and chronic paediatric intensive care patients: current trends and
      perspectives on resource utilization.
AB  - BACKGROUND: Advances in paediatric critical care have resulted in increased
      survival of critically ill patients, many of whom require long-term ventilation
      as a means of life support. AIM: To determine current trends in resource
      utilization, and problems in the care of acute and chronic paediatric intensive
      care patients. DESIGN: Open observational study. METHODS: We evaluated
      consecutive admissions (n = 1629) to a 10-bed paediatric intensive care unit
      (PICU) over a 5-year period. Three previously defined criteria for resource
      utilization were used: mean length of stay (LOS); length of mechanical
      ventilation (LOMV); and LOMV/LOS ratio. RESULTS: A total of 10 310 patient bed
      days and 5223 ventilator days were used. Mean LOS increased from 5.3 +/- 12 days
      in 1998 to 8.7 +/- 27 days in 2001 (p < 0.05). Although LOMV/LOS ratio (50.7%)
      was significantly correlated with Paediatric Risk of Mortality score (p <
      0.0001), there was no significant change in mortality rate (12.6% vs. 12%).
      Patients hospitalized for >2 weeks (n = 320, 20%) used 55% of LOS and 57% of
      LOMV, in contrast to the 1298 (80%) hospitalized for <7 days, who used only 29%
      of LOS and 20% of LOMV. Patients hospitalized for >3 months (11, 0.7%) consumed
      17% of LOS and 23% of LOMV. Five of these (45%) were eventually discharged home,
      two on ventilators. CONCLUSION: The increasing trend of occupation of PICU bed
      and ventilator days by critically ill children may be related to the increasing
      trend for hospitalization of chronic care patients. Severity scoring systems were
      predictive of resource consumption, but not of the overall trend in mortality
      rate.

PMID- 15256609
TI  - Assessment of individual quality of life using the SEIQoL-DW in older medical
      patients.
AB  - BACKGROUND: Many hospital admissions aim to optimize quality of life (QoL).
      However, the standard medical clerking does not systematically record QoL items.
      AIM: To examine whether the current disease-based clerking could be supplemented
      in older people with QoL information. DESIGN: Survey of non-elective admissions
      aged > or = 65 years. METHODS: Participants (n = 60) were interviewed on day 3-5
      of their admission. QoL was measured using the SEIQoL-DW and the SF36 (version
      2). Cognitive and physical function were also assessed. Aspects of feasibility
      and acceptability were explored, and the potential clinical benefits of the
      information investigated. RESULTS: Mean patient age was 81 years; 36 (60%) were
      female. Forty-five completed the SEIQoL-DW, (mean time 37.7 min), of whom 17
      experienced practical difficulties drawing the cue levels, and 25 had difficulty
      manipulating the direct weighting device of the SEIQoL-DW. However, the
      assessment process was judged as acceptable, and elicited more subjective
      information than was recorded in medical and nursing notes. Doctors considered
      the individual QoL information potentially useful for planning discharge and
      follow-up. DISCUSSION: The SEIQoL-DW is probably too time-consuming for standard
      medical clerking. However, as it was judged acceptable by patients, and according
      to medical staff, gives potentially valuable information, there may be
      circumstances in which its use is worthwhile.

PMID- 15256610
TI  - Management of tuberculous constrictive pericarditis and tuberculous pericardial
      effusion in Transkei: results at 10 years follow-up.
AB  - BACKGROUND: Tuberculous pericarditis is common in Transkei (Eastern Cape). Two
      randomized trials showed benefits at two years for prednisolone in patients with
      constrictive pericarditis, and open drainage plus prednisolone in patients with
      pericardial effusion. AIM: To see whether the advantages of prednisolone and open
      drainage were maintained up to 10 years. DESIGN: Follow-up of randomized, double
      blind, placebo-controlled trials. METHODS: All 383 patients (143 constriction,
      240 effusion) received the same anti-tuberculosis chemotherapy. They were
      randomized to prednisolone or placebo for the first 11 weeks, and were followed
      up over 10 years. Among the 240 with effusion, 122 were also randomized to
      immediate open surgical drainage of pericardial fluid versus pericardiocentesis
      as required. Adverse outcomes were: death from pericarditis, pericardiectomy,
      repeat pericardiocentesis, and subsequent open drainage. RESULTS: The 10-year
      follow-up rate was 96%. In constriction patients, adverse outcomes occurred in
      19/70 (27%) prednisolone vs. 28/73 (38%) placebo (p = 0.15), deaths from
      pericarditis being 2 (3%) vs. 8 (11%), respectively (p = 0.098, Fisher's exact
      test). In effusion patients, adverse outcomes occurred in 14/27 (52%) with
      neither drainage nor prednisolone, vs. 4/29 (14%) drainage and prednisolone, 4/35
      (11%) drainage and placebo, and 6/31 (19%) prednisolone and no drainage (p = 0.08
      for interaction). Drainage eliminated the need for repeat pericardiocentesis. In
      the 176 with effusion and no drainage, adverse outcomes occurred in 17/88 (19%)
      prednisolone vs. 35/88 (40%) placebo patients (p = 0.003), with repeat
      pericardiocentesis 20 (23%) placebo vs. 9 (10%) prednisolone (p = 0.025). In a
      multivariate survival analysis (stratified by type of pericarditis), prednisolone
      reduced the overall death rate after adjusting for age and sex (p = 0.044), and
      substantially reduced the risk of death from pericarditis (p = 0.004). At 10
      years, the great majority of surviving patients in all treatment groups were
      either fully active or out and about, even if activity was restricted.
      DISCUSSION: In the absence of a clear contraindication, a corticosteroid should
      be used in addition to antituberculosis chemotherapy in the management of
      patients with tuberculous pericarditis.

PMID- 15256611
TI  - Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling
      hypothesis'.
AB  - Increased oxidative stress in diabetes mellitus may underlie the development of
      endothelial cell dysfunction by decreasing the availability of nitric oxide (NO)
      as well as by activating pro-inflammatory pathways. In the arterial wall, redox
      imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric
      oxide synthase (eNOS). This results in decreased production and increased
      consumption of NO, and generation of free radicals, such as superoxide and
      peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative
      phosphorylation, resulting in inhibition of electron transport and increased
      transfer of electrons to molecular oxygen to form superoxide and other oxidant
      radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of
      the electron transport chain, may improve endothelial dysfunction by 'recoupling'
      eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also
      act synergistically with anti-atherogenic agents, such as fibrates and statins,
      to improve endotheliopathy in diabetes.

PMID- 15256612
TI  - Improving general practitioners' knowledge of chronic hepatitis C infection.

PMID- 15256613
TI  - Patterns of thought.

PMID- 15256614
TI  - Impaled on the invisible.

PMID- 15256615
TI  - Modular construction of early Ediacaran complex life forms.
AB  - Newly discovered, exceptionally preserved, soft-bodied fossils near Spaniard's
      Bay in eastern Newfoundland exhibit features not previously described from
      Ediacaran (terminal Neoproterozoic) fossils. All of the Spaniard's Bay taxa were
      composed of similar architectural elements-centimeter-scale frondlets exhibiting
      three orders of fracticality in branching. Frondlets were combined as modules
      atop semi-rigid organic skeletons to form a wide array of larger constructions,
      including frondose and plumose structures. This architecture and construction
      define the "rangeomorphs," a biological clade that dominated the Mistaken Point
      assemblage (575 to 560 million years ago) but does not appear to be ancestral to
      any Phanerozoic or modern organisms.

PMID- 15256616
TI  - Crystal structures of human cytochrome P450 3A4 bound to metyrapone and
      progesterone.
AB  - Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and
      xenobiotics, such as pollutants, environmental compounds, and drug molecules. The
      microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19,
      CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90%
      of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules
      than all other isoforms combined. Here we report three crystal structures of
      CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate
      progesterone. The structures revealed a surprisingly small active site, with
      little conformational change associated with the binding of either compound. An
      unexpected peripheral binding site is identified, located above a phenylalanine
      cluster, which may be involved in the initial recognition of substrates or
      allosteric effectors.

PMID- 15256617
TI  - Host-to-parasite gene transfer in flowering plants: phylogenetic evidence from
      Malpighiales.
AB  - Horizontal gene transfer (HGT) between sexually unrelated species has recently
      been documented for higher plants, but mechanistic explanations for HGTs have
      remained speculative. We show that a parasitic relationship may facilitate HGT
      between flowering plants. The endophytic parasites Rafflesiaceae are placed in
      the diverse order Malpighiales. Our multigene phylogenetic analyses of
      Malpighiales show that mitochondrial (matR) and nuclear loci (18S ribosomal DNA
      and PHYC) place Rafflesiaceae in Malpighiales, perhaps near Ochnaceae/Clusiaceae.
      Mitochondrial nad1B-C, however, groups them within Vitaceae, near their obligate
      host Tetrastigma. These discordant phylogenetic hypotheses strongly suggest that
      part of the mitochondrial genome in Rafflesiaceae was acquired via HGT from their
      hosts.

PMID- 15256618
TI  - Blood flow patterns in focal liver lesions at microbubble-enhanced US.
AB  - Noninvasive diagnosis of liver lesions is usually performed with contrast
      material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging
      and is based on enhancement features of the arterial and portal venous phases.
      Ultrasonography (US) is often limited in characterizing liver lesions because
      color and spectral Doppler US provide limited vascular information in large
      patients and in small or deep lesions. However, microbubble contrast agents,
      together with specialized US techniques, now allow diagnosis of liver lesions
      based on morphologic evaluation of lesion vascularity and visualization of
      specific enhancement features. Microbubble contrast agents are purely
      intravascular, easy to administer, and well tolerated and allow sensitive real
      time evaluation of blood flow in hepatic lesions. During the portal venous phase,
      benign lesions (eg, hemangioma, focal nodular hyperplasia) typically enhance more
      than the liver, whereas malignant lesions (eg, hepatocellular carcinoma,
      metastases) enhance less. Microbubble-enhanced US allows characterization of very
      small lesions that may not be accurately characterized with CT or MR imaging.
      Findings from initial studies suggest that microbubble-enhanced US of the liver
      provides enhancement information comparable to that provided by contrast-enhanced
      CT and MR imaging, along with real-time morphologic evaluation of lesion
      vascularity.

PMID- 15256619
TI  - The infected liver: radiologic-pathologic correlation.
AB  - Recent technologic advances have significantly enhanced the role of imaging in
      the detection, characterization, and management of infectious diseases involving
      the liver. In addition, imaging-guided percutaneous drainage has greatly improved
      the clinical treatment of patients with focal liver abscess. Infectious liver
      diseases can be accurately evaluated with ultrasonography (US), computed
      tomography (CT), and magnetic resonance (MR) imaging. Characteristic changes in
      US echogenicity, CT attenuation, or MR imaging signal intensity and typical
      enhancement patterns can contribute to the diagnosis of specific infectious
      diseases, including abscesses, parasitic diseases, fungal diseases, granulomatous
      diseases, viral hepatitis, and other less common infections. CT is particularly
      helpful in revealing the presence of calcifications and gas and in detailing the
      enhancement pattern. The multiplanar capability of MR imaging and its sensitivity
      to small differences in tissue composition increase its specificity for certain
      hepatic infections, including hydatid cyst and candidiasis. Radiologic findings
      may be sufficient to obviate aspiration or histologic examination, although in
      most instances they are less specific. Nevertheless, imaging findings taken
      together with appropriate clinical information may provide the most likely
      diagnosis, even if biopsy is sometimes required for confirmation.

PMID- 15256620
TI  - Evaluation of living liver transplant donors: method for precise anatomic
      definition by using a dedicated contrast-enhanced MR imaging protocol.
AB  - Liver transplantation from a living donor involves removal of part of the donor
      liver in a fashion that does not endanger its vascular supply or metabolic
      function. The radiologist plays an important role in evaluation of the living
      donor to define the conditions under which graft donation is contraindicated and
      to identify anatomic variations that may alter the surgical approach. In the
      past, diagnostic work-up of the donor involved costly and invasive tests.
      Currently, dynamic contrast material-enhanced computed tomography and magnetic
      resonance (MR) imaging are the imaging tests performed, each of which has
      advantages and limitations. MR imaging performed with liver-specific and
      extravascular contrast agents may be used as a single imaging test for
      comprehensive noninvasive evaluation of living liver transplant donors. MR
      imaging provides valuable information about variations in the vascular and
      biliary anatomy and allows evaluation of the hepatic parenchyma for diffuse or
      focal abnormalities.

PMID- 15256621
TI  - Multi-detector row CT angiography in patients with abdominal angina.
AB  - Abdominal angina (AA) is an infrequently occurring syndrome characterized by
      postprandial abdominal pain due to reduced blood flow to organs in the territory
      of the celiac trunk, superior mesenteric artery (SMA), and inferior mesenteric
      artery. Multi-detector row computed tomographic (CT) angiography with four- or 16
      row scanners has become a primary tool for the evaluation of patients with
      suspected steno-occlusive diseases of the abdominal vessels. In patients with
      suspected AA, multi-detector row CT angiography can help evaluate the presence
      and degree of stenosis in the celiac trunk and SMA, demonstrate the collateral
      circulation, and help exclude other causes of vascular obstruction. It also
      allows visualization of small vessels and of vessel wall abnormalities in the
      absence of significant stenosis. Vessels with a complex anatomic configuration
      can easily be visualized with proper postprocessing techniques. This modality can
      also be used to follow up patients who have undergone percutaneous interventional
      treatment. Limitations include the lack of dynamic representation of flow
      abnormalities and difficulty in evaluating heavily calcified vessels.
      Nevertheless, multi-detector row CT angiography with appropriate postprocessing
      techniques is highly effective for the diagnosis, evaluation, and treatment of
      suspected AA. Additional studies will help further evaluate the performance and
      applications of this modality.

PMID- 15256622
TI  - Effects of radiation therapy on the lung: radiologic appearances and differential
      diagnosis.
AB  - Radiation-induced lung disease (RILD) due to radiation therapy is common.
      Radiologic manifestations are usually confined to the lung tissue within the
      radiation port and are dependent on the interval after completion of treatment.
      In the acute phase, RILD typically manifests as ground-glass opacity or
      attenuation or as consolidation; in the late phase, it typically manifests as
      traction bronchiectasis, volume loss, and scarring. However, the use of oblique
      beam angles and the development of newer irradiation techniques such as three
      dimensional conformal radiation therapy can result in an unusual distribution of
      these findings. Awareness of the atypical manifestations of RILD can be useful in
      preventing confusion with infection, recurrent malignancy, lymphangitic
      carcinomatosis, and radiation-induced tumors. In addition, knowledge of
      radiologic findings that are outside the expected pattern for RILD can be useful
      in diagnosis of infection or recurrent malignancy. Such findings include the late
      appearance or enlargement of a pleural effusion; development of consolidation, a
      mass, or cavitation; and occlusion of bronchi within an area of radiation-induced
      fibrosis. A comprehensive understanding of the full spectrum of these
      manifestations is important to facilitate diagnosis and management in cancer
      patients treated with radiation therapy.

PMID- 15256624
TI  - Imaging appearances of lateral ankle ligament reconstruction.
AB  - Six patients were retrospectively identified as having undergone lateral ligament
      reconstruction surgery. The surgical procedures were categorized into four
      groups: direct lateral ligament repair, peroneus brevis tendon rerouting,
      peroneus brevis tendon loop, and peroneus brevis tendon split and rerouting. At
      radiography and magnetic resonance (MR) imaging, the presence of one or more
      suture anchors in the region of the anterior talofibular ligament indicates
      direct ligament repair, whereas a fibular tunnel indicates peroneus brevis tendon
      rerouting or loop. Both ultrasonography (US) and MR imaging demonstrate rerouted
      tendons as part of lateral ankle reconstruction; however, MR imaging can also
      depict the rerouted tendon within an osseous tunnel if present, especially if T1
      weighted sequences are used. Artifact from suture material may obscure the tendon
      at MR imaging but not at US. With both modalities, the integrity of the rerouted
      peroneus brevis tendon is best evaluated by following the tendon proximally from
      its distal attachment site, which typically remains unchanged. The rerouted
      tendon or portion of the tendon can then be traced proximally to its reattachment
      site. Familiarity with the surgical procedures most commonly used for lateral
      ankle ligament reconstruction, and with the imaging features of these procedures,
      is essential for avoiding diagnostic pitfalls and ensuring accurate assessment of
      the ligament reconstruction.

PMID- 15256625
TI  - Musculoskeletal colloquialisms: how did we come up with these names?
AB  - Eponyms and colloquial terms are labels that provide two kinds of information:
      the pattern of a complex injury or pathologic problem and, in the case of an
      eponym, the name of an individual who has been closely identified with the
      pathologic problem. Such terms remind us that the medicine of today is not
      entirely the work of our contemporaries. The article illustrates many of the
      common colloquial terms applied to fractures and musculoskeletal injuries seen in
      everyday practice. Wherever possible, the illustrations and definitions are based
      on the original descriptions of the injuries.

PMID- 15256626
TI  - Practice corner: food for thought: Americans are shrinking--but why?

PMID- 15256627
TI  - Imaging findings in musculoskeletal complications of AIDS.
AB  - Patients with human immunodeficiency virus (HIV) infection and acquired
      immunodeficiency syndrome (AIDS) are susceptible to a variety of complications
      that can affect the musculoskeletal system. These complications can be
      infectious, inflammatory, or neoplastic or can take some other form. Infection
      (cellulitis, necrotizing fasciitis, soft-tissue abscess, pyomyositis,
      osteomyelitis, septic arthritis) is the most common complication. Inflammatory
      processes include various arthritides as well as polymyositis. Non-Hodgkin
      lymphoma and Kaposi sarcoma are the two most common neoplasms in this patient
      population. Miscellaneous disorders include osteonecrosis, osteoporosis,
      rhabdomyolysis, anemia-related abnormal bone marrow, and hypertrophic
      osteoarthropathy. The underlying mechanisms leading to these diseases are complex
      and not fully understood but are thought to be multifactorial. Radiology may play
      an important role in early diagnosis and treatment planning in this population,
      in whom clinical and laboratory findings are commonly equivocal and nonspecific.
      Although biopsy is often necessary for the final diagnosis, it is important for
      the radiologist to be familiar with the different types of musculoskeletal
      disease in HIV-positive and AIDS patients so that an appropriate differential
      diagnosis can be established.

PMID- 15256628
TI  - Radiologic manifestations of Proteus syndrome.
AB  - Proteus syndrome is a sporadic disorder named for its highly variable
      manifestations. The disease causes tissue overgrowth in a mosaic pattern and may
      affect tissues derived from any germinal layer. The disease process is not
      usually apparent at birth but develops rapidly in childhood. Common
      manifestations include macrodactyly, vertebral abnormalities, asymmetric limb
      overgrowth and length discrepancy, hyperostosis, abnormal and asymmetric fat
      distribution, asymmetric muscle development, connective-tissue nevi, and vascular
      malformations. The features of Proteus syndrome indicate that the condition may
      be caused by a somatic alteration in a gene, but no specific genetic mutation has
      yet been identified. Therefore, the diagnosis and management of the disease
      depend heavily on clinical evaluation and imaging. Although the manifestations of
      Proteus syndrome are highly variable, accurate diagnosis is possible if standard
      diagnostic criteria are followed and if disease features are assessed in
      comparison with those found in similar syndromes.

PMID- 15256629
TI  - Imaging findings in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an unusually complex autoimmune disease
      that is encountered in every radiology subspecialty because of its multisystem
      involvement and the wide age range of affected patients. There are no universally
      accepted diagnostic imaging criteria for SLE, and in fact, many SLE patients
      present with systemic findings and laboratory abnormalities and do not require
      imaging. Nevertheless, radiology plays an ancillary role in the diagnosis and
      management of this often insidious disease, and knowledge of the spectrum of
      radiologic findings in SLE and its complications is crucial for proper image
      interpretation. Imaging is often performed in patients with a known diagnosis of
      SLE to determine the extent and severity of disease, which depend on the extent
      of organ involvement, and to monitor complications. In addition, imaging may be
      important in selected patients with diseases such as pneumonia who present with
      atypical symptoms due to immunosuppressive therapy.

PMID- 15256630
TI  - Vascular injuries of the neck and thoracic inlet: helical CT-angiographic
      correlation.
AB  - Imaging evaluation of patients suspected to have arterial injuries of the neck
      has traditionally been performed by using conventional angiography as an
      alternative to surgical exploration. However, there has been recent interest in
      and growing experience with use of noninvasive imaging techniques for the
      assessment of vascular injuries. Contrast material-enhanced helical computed
      tomographic (CT) angiography is increasingly being used to evaluate trauma
      patients in stable condition who are at risk for vascular injuries. It allows
      characterization of traumatic vascular lesions in the neck such as partial or
      complete occlusion, pseudoaneurysm, intimal flap, dissection, and arteriovenous
      fistula. In the same setting, CT angiography provides valuable additional
      information about the cervical soft tissues, aerodigestive tract, spinal canal,
      and spinal cord. In cases of penetrating gunshot injuries, the trajectory of the
      bullet and the locations of fragments can be assessed. CT angiography may be
      limited by artifacts from metallic fragments and occasionally by abundant soft
      tissue air or streak artifacts in the shoulders. In such cases, conventional
      angiography is necessary for optimal assessment of vascular injuries. CT
      angiography can be used as a noninvasive alternative to conventional angiography
      in patients suspected to have vascular injuries but without initial indications
      for surgical treatment.

PMID- 15256632
TI  - Radionuclide imaging of the parathyroid glands: patterns, pearls, and pitfalls.
AB  - Optimal parathyroid scintigraphy requires an understanding of (a) the
      embryologic, anatomic, and physiologic features of the parathyroid glands and (b)
      the properties of the two common imaging agents, technetium-99m sestamibi and Tc
      99m tetrofosmin. Normal parathyroid glands are too small to be visualized, but
      parathyroid disease often produces visibly enlarged glands. Enlarged parathyroid
      glands may be found near the thyroid gland or outside their expected locations.
      Characteristic abnormal scintigraphic patterns may be described as focal or
      multifocal, usual or ectopic in location, and associated with a normal or
      abnormal thyroid gland. Patients who are referred for parathyroid imaging should
      have an abnormal biochemical profile. The first step in evaluating images of a
      patient suspected to have parathyroid disease is correlating the normal or
      abnormal scintigraphic patterns with the clinical and surgical history. By
      integrating the interpretative and technical pearls and pitfalls of parathyroid
      scintigraphy, the radiologist can be more confident in establishing a correct
      diagnosis and can precisely guide the surgeon to a single parathyroid adenoma,
      multiple parathyroid adenomas, or multigland hyperplasia.

PMID- 15256633
TI  - From the RSNA refresher courses: imaging evaluation for acute pain in the right
      upper quadrant.
AB  - Acute cholecystitis is the most common cause of acute pain in the right upper
      quadrant (RUQ), and urgent surgical removal of the gallbladder is the treatment
      of choice for uncomplicated disease. However, cross-sectional imaging is
      essential because more than one-third of patients with acute RUQ pain do not have
      acute cholecystitis. In addition, patients with complications of acute
      cholecystitis, such as perforation, are often best treated with supportive
      measures initially and elective cholecystectomy at a later date. Ultrasound (US)
      is the primary imaging modality for assessment of acute RUQ pain; US is both
      sensitive and specific in demonstrating gallstones, biliary dilatation, and
      features that suggest acute inflammatory disease. Occasionally, additional
      imaging modalities are indicated. Computed tomography is valuable, especially for
      confirming the extent and nature of the complications of acute cholecystitis.
      Magnetic resonance cholangiopancreatography is helpful in complicated ductal
      disease (eg, recurrent pyogenic cholangiohepatitis) when more detailed diagnostic
      information is required for treatment planning, whereas endoscopic retrograde
      cholangiopancreatography is used when biliary intervention is required (eg,
      treatment of choledocholithiasis). Successful imaging with all modalities
      requires familiarity with both the characteristic and the unusual features of a
      wide variety of pathologic conditions. In addition, potential pitfalls must be
      recognized and avoided.

PMID- 15256634
TI  - From the archives of the AFIP: primary vascular neoplasms of the spleen:
      radiologic-pathologic correlation.
AB  - Primary vascular neoplasms of the spleen constitute the majority of
      nonhematolymphoid splenic tumors. The benign primary vascular tumors include
      hemangioma, hamartoma, and lymphangioma, whereas those of variable or uncertain
      biologic behavior include littoral cell angioma, hemangioendothelioma, and
      hemangiopericytoma. The primary malignant vascular neoplasm of the spleen is
      angiosarcoma. Peliosis is a rare lesion of unknown cause that is usually found
      incidentally in asymptomatic patients but may be associated with hematologic or
      metastatic disease. Although these vascular neoplasms of the spleen are uncommon,
      their importance lies in that they must be differentiated from the more common
      neoplastic disorders of the spleen, such as lymphoma and metastasis. The most
      common echogenic solid or complex cystic mass in an asymptomatic patient is
      splenic hemangioma. However, the imaging appearance of splenic hemangiomas may be
      complex, and differentiation of these lesions from malignant disease may not be
      possible. The diagnosis of splenic hamartoma may be suggested when findings of
      increased blood flow on color Doppler images are seen in association with a
      homogeneous solid echogenic mass. A large subcapsular solitary cystic abnormality
      discovered incidentally in a child in association with internal septations and
      tiny mural nodules favors the diagnosis of lymphangioma. Any invasion of the
      surrounding splenic parenchyma by a splenic lesion should indicate a more
      aggressive or malignant process. Evaluation of a focal splenic abnormality
      identified on sonograms should be followed up with computed tomography or
      magnetic resonance imaging with and without contrast material enhancement.
      Splenectomy may be required for definitive evaluation of a splenic mass with
      atypical features.

PMID- 15256635
TI  - Best cases from the AFIP: congenital intracranial teratoma.

PMID- 15256636
TI  - Bouveret syndrome.

PMID- 15256637
TI  - Education techniques for lifelong learning: making a PowerPoint presentation.
AB  - Most radiologists are now creating their own image and text slides for oral
      presentations. PowerPoint software offers a tremendous number of options for
      personalizing slides. Having choices of font, color scheme, display options,
      sound, and graphics provide an opportunity to enhance a presentation in ways that
      were not possible with 35-mm slides and slide projectors. However, inappropriate
      use of PowerPoint features can substantially degrade the quality of a
      presentation. Many of the "rules" for creating an effective presentation given
      with slide projectors apply to electronic presentations, but some of the options
      available with only electronic presentations (eg, building, transitioning, and
      sound) necessitate new "rules." The article provides tips on how to develop
      effective text and image slides for electronic presentation by using PowerPoint,
      including the appropriate use of text, font, color, sound, graphics, slide
      display, and radiologic images.

PMID- 15256638
TI  - Education techniques for lifelong learning: giving a PowerPoint presentation: the
      art of communicating effectively.
AB  - Effectiveness of an oral presentation depends on the ability of the speaker to
      communicate with the audience. An important part of this communication is
      focusing on two to five key points and emphasizing those points during the
      presentation. Every aspect of the presentation should be purposeful and directed
      at facilitating learners' achievement of the objectives. This necessitates that
      the speaker has carefully developed the objectives and built the presentation
      around attainment of the objectives. The best presentations are rehearsed, not so
      that the speaker memorizes exactly what he or she will say, but to facilitate the
      speaker's ability to interact with the audience and portray a relaxed,
      professional, and confident demeanor. Rehearsal also helps alleviate stage
      fright. The most useful method of controlling nervousness is to visualize
      success. When showing images, it is important to orient the audience with an
      adequate description, point out the relevant findings, and allow enough time for
      the audience to assimilate the information before moving on. This can be
      facilitated with appropriate use of a laser pointer, cursor, or use of builds and
      transitioning. A presentation should be designed to include as much audience
      participation as possible, no matter the size of the audience. Techniques to
      encourage audience participation include questioning, brainstorming, small-group
      activities, role-playing, case-based examples, and directed listening. It is
      first necessary to motivate and gain attention of the learner for learning to
      take place. This can be accomplished through appropriate use of humor, anecdotes,
      and quotations. Attention should be given to posture, body movement, eye contact,
      and voice when speaking, as how one appears to the audience will have an impact
      on their reaction to what is presented.

PMID- 15256639
TI  - Informatics in radiology (infoRAD): portable toolkit for providing
      straightforward access to medical image data.
AB  - Computer-aided analysis of medical images usually involves the development of
      custom software applications that interpret, process, and ultimately display
      medical image data. The interpretation stage involves decoding the image data and
      presenting them to the application developer for further processing. A toolkit
      has been created specifically for interpreting medical image data; it thus acts
      as a platform for development of medical imaging applications. The toolkit, which
      is referred to as NeatMed, is intended to reduce development time by eliminating
      the need for the application developer to deal directly with medical image data.
      NeatMed was implemented by using Java, a programming language with a range of
      attractive features including ease of use, extensive support material, and
      portability. NeatMed was developed specifically for use in a research
      environment. Straightforward to use and well documented, it is intended as an
      alternative to commercially available medical imaging toolkits. NeatMed currently
      provides support for the Digital Imaging and Communications in Medicine and
      Analyze medical image file formats. Support material including sample source code
      is available via the Internet; links to related resources are also provided. Most
      important, NeatMed is freely available and its continuing development is
      motivated by requests and suggestions from end users.

PMID- 15256640
TI  - Informatics in radiology (infoRAD): A complete continuous-availability PACS
      archive server.
AB  - The operational reliability of the picture archiving and communication system
      (PACS) server in a filmless hospital environment is always a major concern
      because server failure could cripple the entire PACS operation. A simple, low
      cost, continuous-availability (CA) PACS archive server was designed and
      developed. The server makes use of a triple modular redundancy (TMR) system with
      a simple majority voting logic that automatically identifies a faulty module and
      removes it from service. The remaining two modules continue normal operation with
      no adverse effects on data flow or system performance. In addition, the server is
      integrated with two external mass storage devices for short- and long-term
      storage. Evaluation and testing of the server were conducted with laboratory
      experiments in which hardware failures were simulated to observe recovery time
      and the resumption of normal data flow. The server provides maximum uptime
      (99.999%) for end users while ensuring the transactional integrity of all
      clinical PACS data. Hardware failure has only minimal impact on performance, with
      no interruption of clinical data flow or loss of data. As hospital PACS become
      more widespread, the need for CA PACS solutions will increase. A TMR CA PACS
      archive server can reliably help achieve CA in this setting.

PMID- 15256641
TI  - Science, law, and the IBM case.

PMID- 15256642
TI  - Science budgets. U.K. government promises to shore up Britain's science base.

PMID- 15256643
TI  - Cancer. Gleevec, chapter two: new leukemia drug aims to overcome resistance.

PMID- 15256644
TI  - Climate change. Moscow meeting bogged down in acrimony.

PMID- 15256645
TI  - Infectious diseases. Avian influenza makes a comeback, reviving pandemic worries.

PMID- 15256646
TI  - Condensed-matter physics. Single-electron spin measurement heralds deeper look at
      atoms.

PMID- 15256647
TI  - Grants management. Japan taps scientists to improve reviews.

PMID- 15256649
TI  - Particle physics. Japanese detector brings neutrinos into sharper focus.

PMID- 15256648
TI  - U.S. science policy. Report accuses Bush Administration, again, of 'politicizing'
      science.

PMID- 15256650
TI  - Pain research. Prolonging the agony.

PMID- 15256651
TI  - Pain research. Why other people may not feel your pain.

PMID- 15256652
TI  - Japan. Conservation takes a front seat as university builds new campus.

PMID- 15256653
TI  - Jean Jaubert profile. Keeping Jacques Cousteau's flame alive.

PMID- 15256654
TI  - Microbiology. Researchers trade insights about gene swapping.

PMID- 15256655
TI  - Using ethanol as an energy source.

PMID- 15256656
TI  - A response from IBM.

PMID- 15256657
TI  - Prion diseases and a penchant for brains.

PMID- 15256658
TI  - Ecology. Ecosystem-based fishery management.

PMID- 15256659
TI  - Physics. Music of the spheres at the atomic scale.

PMID- 15256660
TI  - Physiology. Heeding the hormonal call.

PMID- 15256661
TI  - Biochemistry. Completing the view of transcriptional regulation.

PMID- 15256662
TI  - Ocean science. The fate of industrial carbon dioxide.

PMID- 15256663
TI  - The evolution of modern eukaryotic phytoplankton.
AB  - The community structure and ecological function of contemporary marine ecosystems
      are critically dependent on eukaryotic phytoplankton. Although numerically
      inferior to cyanobacteria, these organisms are responsible for the majority of
      the flux of organic matter to higher trophic levels and the ocean interior.
      Photosynthetic eukaryotes evolved more than 1.5 billion years ago in the
      Proterozoic oceans. However, it was not until the Mesozoic Era (251 to 65 million
      years ago) that the three principal phytoplankton clades that would come to
      dominate the modern seas rose to ecological prominence. In contrast to their
      pioneering predecessors, the dinoflagellates, coccolithophores, and diatoms all
      contain plastids derived from an ancestral red alga by secondary symbiosis. Here
      we examine the geological, geochemical, and biological processes that contributed
      to the rise of these three, distantly related, phytoplankton groups.

PMID- 15256664
TI  - Impact of anthropogenic CO2 on the CaCO3 system in the oceans.
AB  - Rising atmospheric carbon dioxide (CO2) concentrations over the past two
      centuries have led to greater CO2 uptake by the oceans. This acidification
      process has changed the saturation state of the oceans with respect to calcium
      carbonate (CaCO3) particles. Here we estimate the in situ CaCO3 dissolution rates
      for the global oceans from total alkalinity and chlorofluorocarbon data, and we
      also discuss the future impacts of anthropogenic CO2 on CaCO3 shell-forming
      species. CaCO3 dissolution rates, ranging from 0.003 to 1.2 micromoles per
      kilogram per year, are observed beginning near the aragonite saturation horizon.
      The total water column CaCO3 dissolution rate for the global oceans is
      approximately 0.5 +/- 0.2 petagrams of CaCO3-C per year, which is approximately
      45 to 65% of the export production of CaCO3.

PMID- 15256665
TI  - The oceanic sink for anthropogenic CO2.
AB  - Using inorganic carbon measurements from an international survey effort in the
      1990s and a tracer-based separation technique, we estimate a global oceanic
      anthropogenic carbon dioxide (CO2) sink for the period from 1800 to 1994 of 118
      +/- 19 petagrams of carbon. The oceanic sink accounts for approximately 48% of
      the total fossil-fuel and cement-manufacturing emissions, implying that the
      terrestrial biosphere was a net source of CO2 to the atmosphere of about 39 +/-
      28 petagrams of carbon for this period. The current fraction of total
      anthropogenic CO2 emissions stored in the ocean appears to be about one-third of
      the long-term potential.

PMID- 15256666
TI  - Phase-resolved spectroscopy of Geminga shows rotating hot spot(s).
AB  - Isolated neutron stars are seen in x-rays through their nonthermal and/or surface
      thermal emissions. X-ray Multimirror Mission-Newton observations of the Geminga
      pulsar show a 43-electron volt spectrum from the whole neutron star surface, as
      well as a power-law component above 2 kiloelectron volts. In addition, we have
      detected a hot (170 electron volts) thermal emission from an approximately 60
      meter-radius spot on the pulsar's surface. Such a thermal emission, only visible
      at selected phase intervals, may be coming from polar hot spot(s), long thought
      to exist as a result of heating from magnetospheric accelerated particles. It may
      provide the missing link between the x-ray and gamma-ray emission of the pulsar.

PMID- 15256667
TI  - Electronic transitions in perovskite: possible nonconvecting layers in the lower
      mantle.
AB  - We measured the spin state of iron in magnesium silicate perovskite
      (Mg(0.9),Fe(0.1))SiO(3) at high pressure and found two electronic transitions
      occurring at 70 gigapascals and at 120 gigapascals, corresponding to partial and
      full electron pairing in iron, respectively. The proportion of iron in the low
      spin state thus grows with depth, increasing the transparency of the mantle in
      the infrared region, with a maximum at pressures consistent with the D" layer
      above the core-mantle boundary. The resulting increase in radiative thermal
      conductivity suggests the existence of nonconvecting layers in the lowermost
      mantle.

PMID- 15256668
TI  - Structure and flexibility adaptation in nonspecific and specific protein-DNA
      complexes.
AB  - Interaction of regulatory DNA binding proteins with their target sites is usually
      preceded by binding to nonspecific DNA. This speeds up the search for the target
      site by several orders of magnitude. We report the solution structure and
      dynamics of the complex of a dimeric lac repressor DNA binding domain with
      nonspecific DNA. The same set of residues can switch roles from a purely
      electrostatic interaction with the DNA backbone in the nonspecific complex to a
      highly specific binding mode with the base pairs of the cognate operator
      sequence. The protein-DNA interface of the nonspecific complex is flexible on
      biologically relevant time scales that may assist in the rapid and efficient
      finding of the target site.

PMID- 15256669
TI  - Spatial coordination of cytokinetic events by compartmentalization of the cell
      cortex.
AB  - During cytokinesis, furrow ingression and plasma membrane fission irreversibly
      separate daughter cells. How actomyosin ring assembly and contraction, vesicle
      fusion, and abscission are spatially coordinated was unknown. We found that
      during cytokinesis septin rings, located on both sides of the actomyosin ring,
      acted as barriers to compartmentalize the cortex around the cleavage site.
      Compartmentalization maintained diffusible cortical factors, such as the exocyst
      and the polarizome, to the site of cleavage. In turn, such factors were required
      for actomyosin ring function and membrane abscission. Thus, a specialized
      cortical compartment ensures the spatial coordination of cytokinetic events.

PMID- 15256670
TI  - The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA
      cells.
AB  - Vertebrate limb outgrowth is driven by a positive feedback loop involving Sonic
      Hedgehog (Shh), Gremlin, and Fgf4. By overexpressing individual components of the
      loop at a time after these genes are normally down-regulated in chicken embryos,
      we found that Shh no longer maintains Gremlin in the posterior limb. Shh
      expressing cells and their descendants cannot express Gremlin. The proliferation
      of these descendants forms a barrier separating the Shh signal from Gremlin
      expressing cells, which breaks down the Shh-Fgf4 loop and thereby affects limb
      size and provides a mechanism explaining regulative properties of the limb bud.

PMID- 15256671
TI  - Overriding imatinib resistance with a novel ABL kinase inhibitor.
AB  - Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic
      myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL
      kinase domain point mutations that interfere with drug binding. Crystallographic
      studies predict that most imatinib-resistant mutants should remain sensitive to
      inhibitors that bind ABL with less stringent conformational requirements. BMS
      354825 is an orally bioavailable ABL kinase inhibitor with two-log increased
      potency relative to imatinib that retains activity against 14 of 15 imatinib
      resistant BCR-ABL mutants. BMS-354825 prolongs survival of mice with BCR-ABL
      driven disease and inhibits proliferation of BCR-ABL-positive bone marrow
      progenitor cells from patients with imatinib-sensitive and imatinib-resistant
      CML. These data illustrate how molecular insight into kinase inhibitor resistance
      can guide the design of second-generation targeted therapies.

PMID- 15256672
TI  - Steroid-dependent auditory plasticity leads to adaptive coupling of sender and
      receiver.
AB  - For seasonally breeding vertebrates, reproductive cycling is often coupled with
      changes in vocalizations that function in courtship and territoriality. Less is
      known about changes in auditory sensitivity to those vocalizations. Here, we show
      that nonreproductive female midshipman fish treated with either testosterone or
      17beta-estradiol exhibit an increase in the degree of temporal encoding of the
      frequency content of male vocalizations by the inner ear that mimics the
      reproductive female's auditory phenotype. This sensory plasticity provides an
      adaptable mechanism that enhances coupling between sender and receiver in vocal
      communication.

PMID- 15256673
TI  - Cognitive imitation in rhesus macaques.
AB  - Experiments on imitation typically evaluate a student's ability to copy some
      feature of an expert's motor behavior. Here, we describe a type of observational
      learning in which a student copies a cognitive rule rather than a specific motor
      action. Two rhesus macaques were trained to respond, in a prescribed order, to
      different sets of photographs that were displayed on a touch-sensitive monitor.
      Because the position of the photographs varied randomly from trial to trial,
      sequences could not be learned by motor imitation. Both monkeys learned new
      sequences more rapidly after observing an expert execute those sequences than
      when they had to learn new sequences entirely by trial and error.

PMID- 15256676
TI  - Apoptotic and necrotic death mechanisms are concomitantly activated in the same
      cell after cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Both necrotic and apoptotic cell death mechanisms are
      activated after cerebral ischemia. However, whether they are concomitantly active
      in the same cell or in discrete cell populations is not known. METHODS: We
      investigated activation of both pathways at the cellular level in mice brains
      subjected to transient or permanent focal ischemia. RESULTS: Four hours after
      ischemia, diffuse cathepsin-B spillage into cytoplasm, suggesting lysosomal
      leakage, was observed within neurons immunoreactive for the active form of
      caspase-3 (p20). Ischemic neurons with a leaky plasma membrane (positive for
      propidium iodide) were colabeled with caspase-cleaved actin fragment and
      exhibited TUNEL-positive nuclei having apoptotic morphology. At 72 hours, up to
      27% of cells with caspase activity displayed morphological features suggestive of
      secondary necrosis. CONCLUSIONS: These data, demonstrating an early and
      concurrent increase in caspase-3 and cathepsin-B activities followed by
      appearance of caspase-cleavage products, DNA fragmentation, and membrane
      disintegration, suggest that subroutines of necrotic and apoptotic cell death are
      concomitantly activated in ischemic neurons and that the dominant cell death
      phenotype is determined by the relative speed of each process.

PMID- 15256675
TI  - Long-term angiotensin-converting enzyme inhibitor perindopril therapy improves
      cerebral perfusion reserve in patients with previous minor stroke.
AB  - BACKGROUND AND PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor-based
      therapy reduces the recurrence of stroke. The present study assessed the effects
      of long-term ACE inhibitor therapy on cerebral circulation in patients with
      previous minor stroke. METHODS: After a run-in period, 19 patients were
      randomized to ACE inhibitor therapy (n=9; 4 mg of perindopril daily; mean age,
      64+/-8 years; mean systolic/diastolic blood pressure [BP]+/-SD, 133+/-12/77+/-9
      mm Hg) or placebo therapy (n=10; mean age, 66+/-9 years; mean BP, 139+/-10/78+/-8
      mm Hg). Cerebral blood flow (CBF) was measured during hypercapnia, normocapnia,
      and hypocapnia using a positron emission tomography with H2(15)O at entry into
      the study and after 3 to 12 months. Cerebral perfusion reserve (CPR) was defined
      as percent CBF response to a 1 mm Hg change in arterial partial pressure of CO2
      between hypercapnia and hypocapnia. RESULTS: Systolic/diastolic BP and CBF during
      normocapnia showed no significant changes between entry and completion of the
      trial in the perindopril and placebo groups. Mean value of CPR showed a
      significant increase in the perindopril group (from 3.7+/-1.7%/mm Hg to 4.8+/
      1.7%/mm Hg; P<0.05) but not in the placebo group (from 4.1+/-0.8%/mm Hg to 4.2+/
      0.6%/mm Hg; NS). Statistical parametric mapping analysis also showed global and
      significant increase (P<0.01, uncorrected) in CPR in the perindopril group alone.
      CONCLUSIONS: Long-term ACE inhibitor-based therapy had a beneficial effect on the
      cerebral circulation by improving CPR in patients with previous minor stroke.

PMID- 15256677
TI  - Gender differences in the relationship between periodontal disease, tooth loss,
      and atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Males carry a disproportionate burden of cardiovascular
      disease. Because males also bear a higher burden of periodontal disease, we
      investigated the existence of gender differences in the postulated relationship
      between periodontal infections, tooth loss, and subclinical atherosclerosis.
      METHODS: A total of 1710 randomly enrolled participants between the ages of 45
      and 75 with no history of myocardial infarction or stroke received a clinical
      periodontal examination, carotid scan using high-resolution B-mode ultrasound,
      and extensive measurements for conventional cardiovascular risk factors (age,
      education, smoking, alcohol, body mass index, diabetes, systolic blood pressure,
      low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and
      triglycerides) as well as markers of healthy lifestyle and social network.
      RESULTS: In both genders, measures of current and long-term periodontitis
      worsened as tooth loss increased. In males but not females, an approximately 10%
      difference in carotid artery plaque prevalence was observed between the lowest
      and highest tertiles of tooth loss (P<0.05) and long-term periodontitis (P=0.05)
      after multivariate adjustment. Similar patterns were observed for intima-media
      thickness. The influence of gender on carotid artery plaque prevalence was most
      evident among the younger age group (<59 years). Between genders, carotid plaque
      prevalence differed by 10%, 15%, and 25% across increasing levels of tooth loss,
      and by 5%, 15%, and 25% across increasing levels of long-term periodontitis.
      CONCLUSIONS: Our data suggest that tooth loss and long-term periodontitis are
      related to subclinical atherosclerosis in men but not women. Gender variations in
      cardiovascular morbidity or mortality may be explained partly by the differential
      contributions of novel risk factors across genders.

PMID- 15256678
TI  - Time period required for transcranial Doppler monitoring of embolic signals to
      predict recurrent risk of embolic transient ischemic attack and stroke from
      arterial stenosis.
AB  - BACKGROUND AND PURPOSE: We aimed to investigate whether the time period of
      transcranial Doppler monitoring for embolic signals can be reduced without loss
      of clinical yield compared with routinely performed 1-hour monitoring. METHODS:
      Investigations on the basis of a post hoc analysis of a previously published
      cohort of 86 patients (55 men, 31 women; mean age 60.6 years) with a nondisabling
      arterioembolic ischemic event in the anterior circulation within the last 30 days
      (mean 7.3) and an ipsilateral medium-grade or high-grade stenosis of the carotid
      or middle cerebral artery. Patients underwent 1-hour monitoring for embolic
      signals and were followed up prospectively for 6 weeks to evaluate the
      relationship between embolic signals and risk of an early ischemic recurrence.
      Risk was also calculated after fictitious reduction of the monitoring period from
      60 minutes to 50, 40, 30, 20, and 10 minutes, respectively, and compared with the
      results obtained from the 1-hour period. RESULTS: The number of patients positive
      for embolic signals decreased with the decreasing monitoring period. By this, the
      odds ratio of embolic signals for an early ischemic recurrence "decreased" from
      40 (derived from the 1-hour monitoring) to 10 when the monitoring lasted < or =30
      minutes. The relationship between the rate of embolic signals per hour and risk
      of a recurrent stroke is described by an S-shaped curve. As a consequence, risk
      estimated from reduced monitoring periods can differ considerably from that
      derived from the 1-hour monitoring if the signal frequency lies within a medium
      range (eg, between 3 and 15 signals in 30 minutes). CONCLUSIONS: The time period
      of monitoring for embolic signals may be reduced without loss of clinical
      relevant information when signal frequency is low or already high during the
      reduced monitoring period, but it should be prolonged to maximally an hour at
      signal numbers within a medium range. However, our results need to be externally
      validated on an independent cohort of patients or confirmed by a prospective
      study before this modification can be recommended in general.

PMID- 15256679
TI  - Evidence that estrogen suppresses rho-kinase function in the cerebral circulation
      in vivo.
AB  - BACKGROUND AND PURPOSE: Premenopausal women are less susceptible to
      cardiovascular diseases than men or postmenopausal women. Such disease states are
      often associated with increased vascular RhoA/Rho-kinase activity and decreased
      activity of nitric oxide (NO). This study tested whether female gender is
      associated with lower Rho-kinase activity or higher NO activity in cerebral
      arteries in vivo and whether estrogen contributes to any such gender differences.
      METHODS: Changes in basilar artery diameter were measured with the use of a
      cranial window preparation in anesthetized Sprague-Dawley rats. Some female rats
      were ovariectomized (OVX) and treated subcutaneously daily for 14 days with
      vehicle (dimethyl sulfoxide) or 17beta-estradiol. Vascular expression of RhoA or
      Rho-kinase was assessed by Western blotting. RESULTS: The Rho-kinase inhibitor Y
      27632 was selectively approximately 3-fold more potent as a cerebral vasodilator
      in males versus females. Expression of total RhoA or Rho-kinase did not differ
      between males and females. In OVX rats, vasodilator responses to Y-27632
      resembled responses in males. Treatment of OVX rats with 17beta-estradiol
      normalized the vasodilator effects of Y-27632 to be equivalent to responses in
      intact female controls. The NO synthase inhibitor N-nitro-l-arginine methyl ester
      caused approximately 50% greater constriction of the basilar artery in females
      versus males, but responses in OVX rats treated with either vehicle or 17beta
      estradiol did not differ from those recorded in intact females. CONCLUSIONS:
      These data indicate that vascular Rho-kinase function is suppressed in females
      because of the effects of estrogen, whereas the higher NO activity in females is
      estrogen independent.

PMID- 15256680
TI  - Mouse model of microembolic stroke and reperfusion.
AB  - BACKGROUND AND PURPOSE: To test the role of fibrinolysis in stroke, we used a
      mouse model in which preformed 2.5- to 3-microm-diameter fibrin microemboli are
      injected into the cerebral circulation. The microemboli lodge in the downstream
      precapillary vasculature and are susceptible to fibrinolysis. METHODS: We
      injected various doses of microemboli into the internal carotid artery in mice
      and characterized their distribution, effects on cerebral blood flow,
      neurological deficit, infarct area, and spontaneous dissolution. By comparing
      wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we
      analyzed the role of endogenous tPA in acute thrombotic stroke. RESULTS:
      Microemboli cause dose-dependent brain injury. Although moderate doses of
      microemboli are followed by spontaneous reperfusion, they result in reproducible
      injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and
      restoration of blood flow and aggravates ischemic thrombotic infarction in the
      brain. CONCLUSIONS: We describe a microembolic model of stroke, in which degree
      of injury can be controlled by the dose of microemboli injected. Unlike vessel
      occlusion models, this model can be modulated to allow spontaneous fibrinolysis.
      Application to tPA-/- mice supports a key role of endogenous tPA in restoring
      cerebral blood flow and limiting infarct size after thrombosis.

PMID- 15256681
TI  - Physical fitness training for stroke patients.

PMID- 15256682
TI  - Direct assessment of completeness of ascertainment in a stroke incidence study.
AB  - BACKGROUND AND PURPOSE: Validity of comparisons of stroke incidence between
      studies or time periods depends on the completeness of ascertainment.
      Ascertainment cannot be reliably assessed indirectly by statistical methods, such
      as capture-recapture. We report the first use of direct methods to determine the
      completeness of different ascertainment strategies in a population-based stroke
      incidence study (Oxford Vascular Study). METHODS: We assessed completeness of 2
      different ascertainment strategies: the core methods common to most previous
      incidence studies and core plus supplementary methods used in some studies
      (including access to carotid and brain imaging referrals and assessment of
      patients referred as "transient ischemic attack" or "recurrent stroke"). We
      assessed completeness of ascertainment in 2 ways. First, we searched anonymized
      primary care electronic patient records of the whole study population (n=90,542).
      Second, we interviewed and followed-up a high-risk subset of our study
      population: all patients who had an acute coronary or peripheral vascular event
      or a related elective investigation or intervention. RESULTS: 126 strokes were
      ascertained by the core plus supplementary methods, of which only 108 were
      identified by the core methods alone. Only 2 additional incident strokes were
      identified by access to primary care electronic patient records of the whole
      study population. Assessment and follow-up of 1103 high-risk individuals (5.5% of
      our total study population aged older than 60 years) identified 16 incident
      strokes. However, all 16 had already been ascertained by the core plus
      supplementary methods. CONCLUSIONS: The core methods of ascertainment used in
      some stroke incidence studies lead to significant underascertainment. However,
      direct assessment of ascertainment suggests that the supplementary methods used
      in recent studies can lead to near-complete ascertainment.

PMID- 15256683
TI  - Prospective community-based study of stroke in Northern Portugal: incidence and
      case fatality in rural and urban populations.
AB  - BACKGROUND AND PURPOSE: Mortality statistics indicate that Portugal has the
      highest stroke mortality in Western Europe. Data on stroke incidence in Northern
      Portugal, the region with the highest mortality, are lacking. This study was
      designed to determine stroke incidence and case fatality in rural and urban
      populations in Northern Portugal. METHODS: All suspected first-ever-in-a-lifetime
      strokes occurring between October 1998 and September 2000 in 37,290 residents in
      rural municipalities and 86,023 living in the city of Porto were entered in a
      population-based registry. Standard definitions and comprehensive sources of
      information were used for identification of patients who were followed-up at 3
      and 12 months after onset of symptoms. RESULTS: During a 24-month period, 688
      patients with a first-ever stroke were registered, 226 in rural and 462 in urban
      areas. The crude annual incidence was 3.05 (95% CI, 2.65 to 3.44) and 2.69 per
      1000 (95% CI, 2.44 to 2.93) for rural and urban populations, respectively; the
      corresponding rates adjusted to the European standard population were 2.02 (95%
      CI, 1.69 to 2.34) and 1.73 (95% CI, 1.53 to 1.92). Age-specific incidence
      followed different patterns in rural and urban populations, reaching major
      discrepancy for those 75 to 84 years old, 20.2 (95% CI, 16.1 to 25.0) and 10.9
      (95% CI, 9.0 to 12.8), respectively. Case fatality at 28 days was 14.6% (95% CI,
      10.2 to 19.3) in rural and 16.9% (95% CI, 13.7 to 20.6) in urban areas.
      CONCLUSIONS: Stroke incidence in rural and urban Northern Portugal is high
      compared to that reported in other Western Europe regions. The high official
      mortality in our country, which could be explained by a relatively high
      incidence, was not because of a high case fatality rate.

PMID- 15256685
TI  - Relationship between plasma glutathione levels and cardiovascular disease in a
      defined population: the Hisayama study.
AB  - BACKGROUND AND PURPOSE: Glutathione (GSH) appears to have marked antioxidant
      activities and therefore may prevent cardiovascular disease (CVD). However, there
      are very few reports on this subject. In a community-based case-control study, we
      tested the hypothesis that low levels of plasma GSH are closely associated with
      CVD and its clinical types. METHODS: The association between fasting plasma total
      GSH (tGSH) levels and CVD were assessed using conditional logistic regression
      analysis among 134 CVD cases and 435 age- and sex-matched healthy control
      subjects. RESULTS: Mean tGSH concentrations were lower in all CVD cases than in
      the control subjects (3.06 versus 3.71 micromol/L; P=0.0001). Among the CVD
      types, both the cerebral infarction cases (2.98 versus 3.59 micromol/L; P=0.001)
      and cerebral hemorrhage cases (2.51 versus 3.43 micromol/L; P=0.0027) had
      significantly lower tGSH levels than the corresponding control groups had. The
      same tendency was observed for cases of subarachnoid hemorrhage (3.45 versus 3.83
      micromol/L; P=0.36) and myocardial infarction (3.65 versus 3.77 micromol/L;
      P=0.69), but these differences were not statistically significant. After
      adjustment for other confounding factors, the risk of CVD was significantly lower
      in the third (adjusted odds ratio, 041; 95% CI, 0.21 to 0.77) and the fourth
      quartiles (adjusted odds ratio, 0.25; 95% CI, 0.12 to 0.51) than in the first.
      This association was most prominent in patients with lacunar infarction or
      cerebral hemorrhage. CONCLUSIONS: These findings suggest that reduced plasma tGSH
      levels are a risk factor for CVD, especially for cerebral small vessel disease.

PMID- 15256684
TI  - No evidence of involvement of Chlamydia pneumoniae in severe cerebrovascular
      atherosclerosis by means of quantitative real-time polymerase chain reaction.
AB  - BACKGROUND AND PURPOSE: All studies reporting high numbers of Chlamydia
      pneumoniae DNA positives in stroke patients published to date have used
      polymerase chain reaction (PCR) techniques highly prone to generate false
      positive results. The aim of this study was to analyze the prevalence of C.
      pneumoniae DNA in plaques of the carotid artery as well as in peripheral blood by
      means of a new, closed, real-time PCR system. METHODS: Carotid endarterectomy
      specimens and preoperative peripheral blood mononuclear cells (PBMC) of 75
      individuals with severe cerebrovascular atherosclerosis were analyzed by means of
      a C. pneumoniae-specific quantitative ompA-based real-time PCR TaqMan system.
      Plaques were also cultured onto HEp-2 cells. Before the surgical intervention, C.
      pneumoniae-specific IgM, IgG, and IgA as well as C-reactive protein (CRP) levels
      were determined. RESULTS: 89% of all patients studied had C. pneumoniae-specific
      antibodies, but the pathogen was not detected in a single carotid atheroma by
      real-time PCR and cell culture. However, C. pneumoniae DNA was detected in 4 PBMC
      samples (5.3%) at very low levels (<1 inclusion/6 mL EDTA blood). No statistical
      significance was found between symptomatic/asymptomatic patients, C. pneumoniae
      PCR, results and CRP values after correction for multiplicity-of-test adjustment.
      CONCLUSIONS: By means of a closed, highly sensitive, and specific real-time PCR,
      C. pneumoniae was not detected in cerebrovascular atherosclerosis. PCR on PBMC
      was not predictive for endovascular chlamydia infection and most likely stem from
      previous C. pneumoniae respiratory tract infection in individual cases.

PMID- 15256687
TI  - Effect of an amino acid, protein, and carbohydrate mixture on net muscle protein
      balance after resistance exercise.
AB  - This study tests the hypotheses that (a) a mixture of whey protein, amino acids
      (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a
      greater extent than isoenergetic CHO alone after resistance exercise; and (b)
      that the stimulatory effect of a protein, AA, and CHO mixture will last beyond
      the 1st hour after intake. Eight subjects participated in 2 trials. In one
      (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after
      resistance exercise. In the other (CON), 100 g CHO was ingested instead. They
      received a primed constant infusion of L-[2H5]-phenylalanine, and samples from
      femoral artery and vein, and biopsies from vastus lateralis were obtained. The
      area under the curve for net uptake of phenylalanine into muscle above pre-drink
      value was 128+/- 42 mg x leg(- 1) (PAAC) versus 32+/- 10 mg x leg (-1) (CON) for
      the 3 hr after the drink (p =.04). The net protein balance response to the
      mixture consisted of two components, one rapid immediate response, and a smaller
      delayed response about 90 min after drink, whereas in CON only a small delayed
      response was seen. We conclude that after resistance exercise, a mixture of whey
      protein, AA, and CHO stimulated muscle protein synthesis to a greater extent than
      isoenergetic CHO alone. Further, compared to previously reported findings, the
      addition of protein to an AA+ CHO mixture seems to extend the anabolic effect.

PMID- 15256688
TI  - Palatability and voluntary intake of sports beverages, diluted orange juice, and
      water during exercise.
AB  - Palatability and voluntary intake of 4 beverages commonly available to athletes
      were compared in a laboratory exercise protocol designed to mimic aerobic
      training or competitive conditions in which limited time is available for
      drinking. Diluted orange juice (DOJ), homemade 6% carbohydrate-electrolyte sports
      beverage (HCE), commercially available 6% carbohydrate-electrolyte sports
      beverage (CCE), and water (W) were tested. Fifty adult triathletes and runners
      (34 males, 16 females) exercised for 75 min at 80-85% of age-predicted heart
      rate, during which time they were given brief access (60 s) to one of the
      beverages after 30 min and 60 min of exercise. Results indicated that for overall
      palatability, CCE > W, HCE, DOJ; W > DOJ, and for amount of beverage consumed,
      CCE > W, HCE, DOJ; HCE > W, DOJ. The palatability of these beverages varied
      substantially, as did their voluntary intakes during exercise.

PMID- 15256689
TI  - Bone mineral density in young active females: the case of dancers.
AB  - The aim of the study was to evaluate the combined effect of several environmental
      factors on bone mineral density (BMD) in a group of highly active young women.
      Body composition, total body and regional (arms, legs and trunk) BMD, dietary
      intake, menstrual status, training habits, and eating attitudes were assessed in
      37 professional dance students, aged 18 to 26 years. Dancers had higher BMD
      values compared to age- and weight-matched reference population (mean total body
      BMD: 1.185 g/cm2, 9% higher than reference values). No differences were detected
      between currently eumenorrheic and noneumenorrheic dancers; subjects who
      encountered menstrual problems during adolescence had significantly lower BMD
      values compared to counterparts who did not. Regarding dietary intake, dancers in
      the highest quartile of calcium intake (1323 +/-113 mg/d) exhibited significantly
      higher total BMD values than subjects in the other 3 quartiles (p =.04). A
      moderate inverse relationship was found between protein intake and total BMD,
      after controlling for energy and calcium intake (r = - 0.37). Fat-free soft mass
      was the only significant predictor of total BMD, explaining 20% of the variance.
      High levels of calcium intake were associated with high total BMD values. These
      results confirm the beneficial role of long-term and intensive physical activity
      on BMD and further suggest that dancers are not at a greater risk compared to the
      general population for developing osteoporosis, despite their menstrual and
      eating problems.

PMID- 15256690
TI  - Acute Rhodiola rosea intake can improve endurance exercise performance.
AB  - PURPOSE: The purpose of this study was to investigate the effect of acute and 4
      week Rhodiola rosea intake on physical capacity, muscle strength, speed of limb
      movement, reaction time, and attention. METHODS:  PHASE I: A double blind placebo
      controlled randomized study (n= 24) was performed, consisting of 2 sessions (2
      days per session). Day 1: One hour after acute Rhodiola rosea intake (R, 200-mg
      Rhodiola rosea extract containing 3% rosavin + 1% salidroside plus 500 mg starch)
      or placebo (P, 700 mg starch) speed of limb movement (plate tapping test), aural
      and visual reaction time, and the ability to sustain attention (Fepsy Vigilance
      test) were assessed. Day 2: Following the same intake procedure as on day 1,
      maximal isometric knee-extension torque and endurance exercise capacity were
      tested. Following a 5-day washout period, the experimental procedure was
      repeated, with the treatment regimens being switched between groups (session 2).
      PHASE II: A double blind placebo-controlled study (n = 12) was performed.
      Subjects underwent sessions 3 and 4, identical to Phase I, separated by a 4-week
      R/P intake, during which subjects ingested 200 mg R/P per day. RESULTS:  PHASE I:
      Compared with P, acute R intake in Phase I increased (p <.05) time to exhaustion
      from 16.8 +/- 0.7 min to 17.2+/- 0.8 min. Accordingly, VO2peak (p <.05) and
      VCO2peak (p<.05) increased during R compared to P from 50.9 +/- 1.8 ml x min(-1)
      x kg(- )1 to 52.9 +/- 2.7 ml x min(-10) x kg(-1) (VO2peak) and from 60.0 +/- 2.3
      ml x min(-1) x kg(-1) to 63.5+/- 2.7 ml x min(-1) x kg(-1) (VCO2peak). Pulmonary
      ventilation (p =.07) tended to increase more during R than during P (P: 115.9+/-
      7.7 L/min; R: 124.8 +/- 7.7 L/min). All other parameters remained unchanged.
      PHASE II: Four-week R intake did not alter any of the variables measured.
      CONCLUSION: Acute Rhodiola rosea intake can improve endurance exercise capacity
      in young healthy volunteers. This response was not altered by prior daily 4-week
      Rhodiola intake.

PMID- 15256691
TI  - Influence of carbohydrate and age on lymphocyte function following a marathon.
AB  - The influence of 6% carbohydrate ingestion and age on PHA-induced lymphocyte
      proliferation and in vitro cytokine production was studied in 48 runners
      following a competitive marathon. Runners were randomly assigned to carbohydrate
      (C; n = 23) and placebo (P; n= 25) groups, with blood samples taken before,
      immediately after, and 1.5 hr post-race. C versus P ingestion resulted in higher
      plasma glucose, lower plasma cortisol, reduced neutrophilia, and monocytosis
      during recovery, but had no effect on the post-exercise reduction in T
      lymphocytes or NK cells, or on race times. No group differences were observed for
      PHA-induced lymphocyte proliferation or cytokine production. However, for all
      subjects combined, lymphocyte proliferation and IFN-gamma secretion decreased
      significantly below pre-race values by 1.5 hr of recovery, and these were
      negatively correlated with plasma cortisol. Young (<50 years; n = 36) and old
      (>or=50 years; n = 12) runners exhibited parallel post-race declines in
      lymphocyte proliferation and IFN-gamma secretion, with the older group exhibiting
      a 33-59% lower proliferation at each time point. In conclusion, PHA-induced
      lymphocyte proliferation and cytokine production decreased significantly
      following a marathon, and this decrease was strongly linked to cortisol and only
      partially linked to T-cell changes. This decrease occurred in both younger and
      older runners and was not influenced by carbohydrate.

PMID- 15256692
TI  - Effect of endurance training and fasting on renal gluconeogenic enzymes in the
      rat.
AB  - The purpose of this study was to examine the effects of chronic exercise training
      (running 30 m/min, 10% grade, 90 min/d for 8-10 weeks) on specific renal enzyme
      activities involved with the gluconeogenic pathway in the fed and 24-hr fasted
      state in rats. A portion of the kidney (containing the cortex and medulla) was
      homogenized from which cytosolic (c) and mitochondrial (m) fractions were
      separated. Maximal gluconeogenic enzyme activities were assessed for:
      phosphoenolpyruvate carboxykinase (cPEPCK), fructose 1,6-bisphosphatase (cFBP),
      pyruvate carboxylase (mPC), aspartate aminotransferase (cAspAT), alanine
      aminotransferase (cAlaAT), and lactate dehydrogenase (cLDH). In the fed state,
      there was no significant difference between groups in any of the enzymes examined
      (nmoles/min x mg protein-1): cPEPCK (25.8+/- 1.7), cFBP (106.8+/- 7.1), mPC
      (20.7+/- 1.8), cAspAT (1047.1 +/- 38.6), cAlaAT (52.3 +/- 4.3), and cLDH
      (1728.6+/- 163.2). After the 24-hr fast, there was a significant increase in
      cPEPCK (52.4+/- 2.9 and 52.0 +/- 2.1) and mPC (44.6 +/- 4.3 and 47.6 +/- 4.9),
      control and trained, respectively. These results suggest that the maximal enzyme
      activities for cPEPCK and mPC can be augmented as a result of fasting that was
      independent of the training status.

PMID- 15256693
TI  - Fluid and electrolyte intake and loss in elite soccer players during training.
AB  - This study measured fluid balance during a 90-min preseason training session in
      the first team squad (24 players) of an English Premier League football team.
      Sweat loss was assessed from changes in body mass after correction for ingested
      fluids and urine passed. Sweat composition was measured by collection from
      patches attached to the skin at 4 sites. The weather was warm (24-29 degrees C),
      with moderate humidity (46-64%). The mean +/- SD body mass loss over the training
      session was 1.10+/- 0.43 kg, equivalent to a level of dehydration of 1.37 +/-
      0.54% of the pre-training body mass. Mean fluid intake was 971 +/- 303 ml.
      Estimated total mean sweat loss was 2033 +/- 413 ml. Mean sweat electrolyte
      concentrations (mmol/L) were: sodium, 49 +/- 12; potassium, 6.0 +/- 1.3;
      chloride, 43 +/- 10. Total sweat sodium loss of 99+/- 24 mmol corresponds to a
      salt (sodium chloride) loss of 5.8 +/- 1.4 g. Mean urine osmolality measured on
      pre-training samples provided by the players was 666 +/- 311 mosmol/kg (n = 21).
      These data indicate that sweat losses of water and solute in football players in
      training can be substantial but vary greatly between players even with the same
      exercise and environmental conditions. Voluntary fluid intake also shows wide
      inter-individual variability and is generally insufficient to match fluid losses.

PMID- 15256694
TI  - Comparison of water turnover rates in young swimmers in training and age-matched
      non-training individuals.
AB  - Total body water (TBW) and water turnover rates (WTR) of 8 competitive swimmers
      (SW) and 6 age-matched non-training individuals (CON) were determined using
      deuterium oxide dilution and elimination. During the 7-day study, individuals in
      the SW group trained 9 times, swimming on average 42.4 km, while the CON group
      did no regular exercise. Water temperature in the swimming pool was between 26
      and 29 degrees C during training sessions. Body mass at the beginning and end of
      the study period remained essentially the same in the SW (67.8+/- 6.3 kg) and CON
      (61.1 +/- 8.5 kg) groups. Mean +/- SD TBW of the SW (38.7+/- 5.6 L) was similar
      to that of the CON (37.5 +/- 8.0 L). Mean WTR was faster in the SW (54 +/- 18 ml
      x kg x day(- 1) than the CON (28+/- 21 ml x kg x day(-1)). Mean daily urine
      output was similar in the SW (14 +/- 5 ml x kg x day(-1)) and CON (14+/- 3 ml x
      kg x day(-1)). Calculated non-renal daily water loss was faster in the SW (41 +/-
      21 ml x kg x day(-1)) than the CON (13 +/- 20 ml x kg x day(-1)). This study
      demonstrates that WTR are faster in young swimmers who exercise strenuously in
      cool water than in non-training individuals and that the difference was due to
      the approximately 3-times greater non-renal water losses that the exercising
      group incurred. This suggests that exercise-induced increases in sweat rates are
      a major factor in water loss in swimmers training in cool water.

PMID- 15256695
TI  - Zinc and copper biochemical indices of antioxidant status in elite athletes of
      different modalities.
AB  - The purpose of this study was to compare zinc and copper biochemical indices of
      antioxidant status and their relationship in elite athletes of different
      modalities: aerobic with high-impact (triathletes, n = 10 and long-distance
      runners, n = 12), anaerobic with high-impact (short-distance runners, n = 9), and
      anaerobic with low-impact (short-distance swimmers, n = 13). The influence of
      recent dietary intake and body composition was also evaluated. A venous blood
      sample was drawn 16-20 hr after competition for the following measurements:
      packed-cell volume and hemoglobin in blood; copper and zinc in plasma and
      erythrocytes; ceruloplasmin in plasma; superoxide dismutase activity and metal
      lothionein in erythrocytes; and erythrocyte osmotic fragility. Zinc and copper
      intakes were not different in the athlete groups and did not affect the
      biochemical indices measured. Athletes of the long-distance high-impact aerobic
      modalities had higher indices of antioxidant protection (erythrocyte zinc,
      superoxide dismutase activity, and metallothionein) than those of the short
      distance low-impact modalities, suggesting that there is adaptation of the
      antioxidant capacity to the specific training. Significant correlations were
      observed in all athletes between erythrocyte zinc, superoxide dismutase activity,
      and metallothionein consistent with the importance of an adequate zinc status in
      the response of antioxidant mechanisms to intense exercise.

PMID- 15256696
TI  - Alpha-glucosidase inhibitory constituents from Duranta repens.
AB  - Three C-alkylated flavonoids 7-O-alpha-D-glucopyranosyl-3,5-dihydroxy-3'-(4"
      acetoxyl-3"-methylbutyl)-6,4'-dimethoxyflavone (1), 7-O-alpha-D-glucopyranosyl
      3,4'-dihydroxy-3'-(4"-acetoxyl-3"-methylbutyl)-5,6-dimethoxyflavone (2), 3,7,4'
      trihydroxy-3'-(8"-acetoxy-7"-methyloctyl)-5,6-dimethoxyflavone (3) and a trans
      clerodane type diterpenoid (-)-6beta-hydroxy-5beta,8beta,9beta,10alpha-cleroda
      3,13-dien-16,15-olid-18-oic acid (4) are reported from Duranta repens along with
      (+)-hardwickiic acid (5) and (+)-3,13-clerodadien-16,15-olid-18-oic acid (6),
      isolated for the first time from this species. Their structures were established
      on the basis of the spectral methods, especially two dimensional (2D) NMR
      spectroscopy.

PMID- 15256697
TI  - An investigation on the influence of a vinyl pyrrolidone/vinyl acetate copolymer
      on the moisture permeation, mechanical and adhesive properties of aqueous-based
      hydroxypropyl methylcellulose film coatings.
AB  - Polymers for aqueous film coating, such as hydroxypropyl methylcellulose (HPMC),
      often require the inclusion of a plasticizer to reduce brittleness and increase
      flexibility and ductility. A vinyl pyrrolidone/vinyl acetate copolymer (S630) was
      investigated for its influence on HPMC film coating parameters, comparing the
      results with a commonly used plasticizer, polyethylene glycol and another
      copolymer, polyvinyl alcohol. The viscous properties of the solutions and the
      glass transition temperatures of the equivalent polymer films were evaluated. Its
      effect on the film properties, such as appearance, surface roughness, moisture
      permeation and mechanical properties, as well as its ability to promote better
      adhesion of the film coat to the core surface, was compared. S630 was able to
      reduce the viscosity of the polymer solution and glass transition temperature of
      HPMC, as well as, enhance the mechanical properties of the cast film. The
      moisture permeation was slightly reduced but not to the same extent as
      polyethylene glycol. A 10% concentration of S630 increased the adhesive strength
      and toughness of the HPMC film coat. In conclusion, S630 was effective as a film
      former, substrate adhesive and plasticizer. It has the potential to be used to
      replace the more volatile plasticizers which have problems of loss or migration.

PMID- 15256698
TI  - Application of a new mathematical method for the estimation of the mean surface
      area to calculate the percolation threshold of lobenzarit disodium [correction of
      dissodium] salt in controlled release matrices.
AB  - One of the practical handicaps for the application of the percolation theory to
      estimate the percolation threshold of drugs in controlled release systems is the
      fact that the dissolution studies must be carried out so that only one surface of
      the tablet is exposed to the dissolution medium. The aim of this work is to
      estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium
      (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and
      Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle
      method. The whole surface of the tablets was exposed to the dissolution medium.
      For the first time, a new mathematical method is developed to transform the
      amount of drug released in amount released per surface area in order to calculate
      the percolation thershold of LBD. The mathematical method proposed allows to
      calculate, using a new equation, the evolution of the mean surface area (O((t))).
      The new method was validated and three novel results were achieved: A constant
      value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272
      cm(2)); a linear relationship between initial surface area (O((0))) and critical
      time; and a linear relationship between O((t)) and time. Employing the values of
      O((t)), it was possible to calculate for the first time, the percolation
      threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and
      Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.

PMID- 15256699
TI  - New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus
      pendulus.
AB  - Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in
      the isolation of two new and three known bisbenzylisoquinoline alkaloids. The
      structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'
      alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The
      cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are
      reported here for the first time.

PMID- 15256700
TI  - Three novel cantharidin-related compounds from the Chinese blister beetle,
      Mylabris phalerata Pall.
AB  - Three novel cantharidin analogues were isolated from the Chinese blister beetle,
      Mylabris phalerata PALL. (Meloidae), which has been used in traditional Chinese
      medicine for the treatment of cancer. Their structures were determined on the
      basis of heteronuclear multiple-bond connectivity and nuclear Overhauser effect
      spectroscopy experiments, and chemical data confirmed them to be so-called
      cantharimides, in which the anhydride oxygen atoms are replaced by the basic
      amino acid L-lysine, L-ornithine, and L-arginine moieties.

PMID- 15256701
TI  - Determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparations
      using UV-visible spectrophotometry and genetic algorithm based multivariate
      calibration methods.
AB  - Simultaneous determination of binary mixtures pyridoxine hydrochloride and
      thiamine hydrochloride in a vitamin combination using UV-visible
      spectrophotometry and classical least squares (CLS) and three newly developed
      genetic algorithm (GA) based multivariate calibration methods was demonstrated.
      The three genetic multivariate calibration methods are Genetic Classical Least
      Squares (GCLS), Genetic Inverse Least Squares (GILS) and Genetic Regression (GR).
      The sample data set contains the UV-visible spectra of 30 synthetic mixtures (8
      to 40 microg/ml) of these vitamins and 10 tablets containing 250 mg from each
      vitamin. The spectra cover the range from 200 to 330 nm in 0.1 nm intervals.
      Several calibration models were built with the four methods for the two
      components. Overall, the standard error of calibration (SEC) and the standard
      error of prediction (SEP) for the synthetic data were in the range of <0.01 and
      0.43 microg/ml for all the four methods. The SEP values for the tablets were in
      the range of 2.91 and 11.51 mg/tablets. A comparison of genetic algorithm
      selected wavelengths for each component using GR method was also included.

PMID- 15256702
TI  - Orally active CCR5 antagonists as anti-HIV-1 agents 2: synthesis and biological
      activities of anilide derivatives containing a pyridine N-oxide moiety.
AB  - In order to develop orally active CCR5 antagonists, we investigated 1-benzoxepine
      derivatives containing new polar substituents, such as phosphonate, phosphine
      oxide or pyridine N-oxide moieties, as replacements for the previously reported
      quaternary ammonium moiety. Among these compounds, the 2-(alpha
      hydroxybenzyl)pyridine N-oxide 5e exhibited moderate CCR5 antagonistic activity
      and had an acceptable pharmacokinetic profile in rats. Subsequent chemical
      modification was performed and compound (S)-5f possessing the (S)-configuration
      hydroxy group was found to be more active than the (R)-isomer. Replacement of the
      1-benzoxepine ring with a 4-methylphenyl group by a 1-benzazepine ring with a 4
      [2-(butoxy)ethoxy]phenyl group enhanced the activity in the binding assay. In
      addition, introduction of a 3-trifluoromethyl group on the phenyl group of the
      anilide moiety led to greatly increased activity in the HIV-1 envelope-mediated
      membrane fusion assay. In particular, compound (S)-5s showed the most potent CCR5
      antagonistic activity (IC(50)=7.2 nM) and inhibitory effect (IC(50)=5.4 nM) in
      the fusion assay, together with good pharmacokinetic properties in rats.

PMID- 15256703
TI  - Characterization of the CYP3A4 active site by homology modeling.
AB  - Human microsomal cytochrome P450s participate in drug metabolism and
      detoxification. Among them, CYP3A4 is the most important isoform for drug-drug
      interactions. To gain a better understanding of the active site, a homology model
      of CYP3A4 was constructed based on the crystallographic coordinates of mammalian
      CYP2C5. The putative active site is much larger than that of CYP2C5 and is
      divided into three parts (i.e. a proximal and two distal sites from the heme).
      Most residues reported to be important for ligand-binding are located in the
      active site of the model. Moreover, some inhibitors (paclitaxel etc.) docked into
      the model have complementary shapes to the pocket. Pharmacophore docking of 14
      substrates was also performed using Ph4Dock of MOE. Calculated interaction
      energies showed a moderate correlation with the logarithm of apparent K(m)
      values. These results suggest that this model is reliable enough to be used in
      the design of compounds for removing undesirable CYP3A4 inhibition.

PMID- 15256704
TI  - Characterization of the CYP2C8 active site by homology modeling.
AB  - To compare the features of the active sites of CYP2C8, CYP2C9, and CYP2C19,
      homology modeling was performed based on the crystallographic coordinates of
      mammalian CYP2C5. It was found that CYP2C8 has a much larger pocket than the
      other forms due to the existence of an additional pocket. The approach to the
      additional pocket is comprised of Ile102, Ser114, Leu208, Val366, and Ile476, and
      the side chains of Ser114, Val366, and Ile476, which are smaller than the
      corresponding residues in the other CYPs, enable access to the pocket. The
      general features of the active site in the CYP2C8 model are similar to those of
      the previously constructed CYP3A4 model, which may account for the 2 CYPs sharing
      some of their substrates. The CYP2C8 model was validated by examining the bound
      orientation of paclitaxel and showing that it is consistent with the formation of
      the 6-beta hydroxylated derivative during metabolism. Docked paclitaxel was found
      to form a hydrogen bond with the side chain of Asn 99, which is a characteristic
      residue of CYP2C8 and is located in the additional pocket. Descriptors for CYP2C8
      and CYP2C9 substrates were also examined with the molecular operating environment
      (MOE). The descriptor by which CYP2C8 and CYP2C9 substrates were classified most
      distinctly was found to be molar refractivity, which might be related to the
      longer shape and more polar nature of the active site of CYP2C8 in the CYP2C
      subfamily.

PMID- 15256705
TI  - Solid-phase tandem radical addition-cyclization reaction: triethylborane-induced
      reaction of oxime ethers anchored to polymer support.
AB  - Tandem radical addition-cyclization of oxime ethers anchored to polymer support
      was studied. The reaction of oxime ethers with stannyl radical proceeded
      effectively by the use of triethylborane as a radical initiator. The alkyl
      radical addition-cyclization reactions of oxime ether connected with alpha,beta
      unsaturated carbonyl group proceeded under iodine atom-transfer reaction
      conditions to give the functionalized azacycles via two carbon-carbon bonds
      forming process.

PMID- 15256706
TI  - Synthesis of (R)-(+)-tanikolide through stereospecific C-H insertion reaction of
      dichlorocarbene with optically active secondary alcohol derivatives.
AB  - Stereospecific alpha C-H insertion reaction of protected chiral 1,2-glycols, (S)
      1,2-isopropylidenedioxytridecane (3) and ethyl (S)-4,5-isopropylidenedioxy
      pentanoate (4), prepared from (R)-glyceraldehyde acetonide (2), with
      dichlorocarbene generated from CHCl(3)/50% NaOH/cetyltrimethylammonium chloride
      (as ptc.) took place with complete retention of configuration to provide (S)-4
      dichloromethyl-2,2-dimethyl-4-undecyl-1,3-dioxolane (5) and ethyl (S)-3-(4
      dichloromethyl-2,2-dimethyl-1,3-dioxolan-4-yl)-propanoate (8), respectively. The
      ester (8) was transformed to 5 by elongation of the side chain. The glycol
      derivative (5) was converted into O-TBDPS-protected (S)-2-hydroxymethyl-2
      undecyloxirane (16). Reaction of 16 with a cuprate reagent containing homoallylic
      carbon chain followed by oxidative manipulation of the terminal olefin afforded
      (R)-(+)-tanikolide (1).

PMID- 15256707
TI  - 3,5-Nonadiyne isolated from the rhizome of Cachrys ferulacea inhibits endogenous
      nitric oxide release by rat peritoneal macrophages.
AB  - 3,5-Nonadiyne, in vitro, selectively inhibits endogenous nitric oxide release
      (IC(50)=6.7+/-0.8 microM) by rat peritoneal macrophages at doses that do not
      inhibit T cell proliferation. 3,5-Nonadiyne was isolated from root essential oil
      of Cachrys ferulacea (L.) CALESTANI, synonym Prangos ferulacea (L.) LINDLEY,
      obtained by hydrodistillation and spectrometricaly identified unambiguously.

PMID- 15256708
TI  - Effects of cantharidinimides on human carcinoma cells.
AB  - Modification of the cantharidinimide structure led to the discovery of a novel
      class of antitumor compounds. These cantharidinimide derivatives containing
      aliphartic, aryl, and pyridyl groups showed some effect in vitro against HepG2
      and HL-60 cells.

PMID- 15256709
TI  - The inhibition of superoxide anion generation by neutrophils from Viscum
      articulactum.
AB  - Two new flavanones, (2S)-pinocembrin 7-O-[beta-D-apiosyl(1-->2)]-beta-D-glucoside
      (1), and (2S)-pinocembrin 7-O-[cinnamoyl(1-->5)-beta-D-apiosyl(1-->2)]-beta-D
      glucoside (2) together with eighteen known compounds, which include five known
      flavanones, nine benzenoids, one inositol and three triterpenoids, were isolated
      and characterized from fresh Viscum articulactum. Structures of new compounds
      were determined by spectral analysis. Among them, oleanolic acid (18) showed a
      significant inhibition effect on superoxide anion generation by human neutrophils
      in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP).

PMID- 15256710
TI  - New abietane-type diterpenes from the heartwood of Picea morrisonicola.
AB  - New abietane-type diterpenes, 15-acetoxy-7-oxodehydroabietic acid (1),
      picealactones A (2), B (3), and C (4), together with the known 7
      oxodehydroabietic acid (5) were isolated and identified from the heartwood of
      Picea morrisonicola. The structures of 1-4 were determined on the basis of
      spectral data explanation. Compounds 2-4 possessed a rare 5-dehydro-18, 6-olide
      functionality. Compounds 1 and 2 were first isolated from natural source.

PMID- 15256711
TI  - Facile characterization of polymer-supported reagents using cross polarization
      magic angle spinning method in solid state 13C-NMR.
AB  - Polymer-supported (PS) reagents can be easily characterized using a cross
      polarization magic angle spinning method in solid state (13)C-NMR. The technique
      was applied to the characterization of PS-dimethylimidazolidinone, analogue to
      potential heterogeneous dehydrating agent.

PMID- 15256712
TI  - New phenolic principles from Hypericum sampsonii.
AB  - Using the anti-hepatitis B virus (HBV)-producing cell line MS-G2 in vitro
      cultural system-guided screening was performed, and two new benzophenones, 2,6
      dihydroxy-4-[(E)-5-hydroxy-3,7-dimethylocta-2,7-dienyloxy]benzophenone (1) and
      2,6-dihydroxy-4-[(E)-7-hydroxy-3,7-dimethylocta-2-enyloxy]benzophenone (2), a new
      xanthone, hyperxanthone (3), a new bisanthraquinone glycoside, R-(-)-skyrin-6-O
      beta-D-xylopyranoside (4), and 2-caffeoyloxy-3-hydroxy-3-(3,4
      dihydroxyphenyl)propyl alcohol (5), and 16 known compounds were isolated from the
      anti-HBV active fraction of the whole herbs of Hypericum sampsonii. Their
      structures were elucidated using spectroscopic methods, mainly 2D NMR and MS
      spectrometry. Circular dichroism was used to determine the stereochemistry of
      bisanthraquinone glycosides.

PMID- 15256713
TI  - Triterpenoid saponins from the roots of Sophora koreensis.
AB  - From the roots of Sophora koreensis (Fabaceae), three new oleanene-type
      triterpene glycosides, echinosophorosides A(1) (1) and B (2), and acetyl
      subproside II (5), were isolated as their methyl esters, together with the four
      known ones sophoraflavoside I, kudzusaponin SA(3), subproside II, and
      azukisaponin V. The structures of the new saponins were elucidated to be 3-O
      alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1-->2)-beta-D
      glucuronopyranosyl kudzusapogenol A 22-O-alpha-L-arabinopyranoside (1), 3-O-alpha
      L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl abrisapogenol C 22-O-alpha-L-arabinopyranoside (2), and 3-O
      alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1-->2)-beta-D
      glucuronopyranosyl kudzusapogenol A 22-O-acetate (5), respectively. It is
      noteworthy that two arabinopyranosyl moieties in the same molecule,
      echinosophoroside B (2), have different conformations. The conformation of the
      arabinopyranosyl moiety existing in the trisaccharide moiety was determined to be
      (1)C(4), whereas that of the arabinopyranosyl unit at C-22 was identified as
      (4)C(1).

PMID- 15256714
TI  - Purification and structural determination of hematopoietic stem cell-stimulating
      monoacetyldiglycerides from Cervus nippon (deer antler).
AB  - A mixture of monoacetyldiglycerides was newly isolated from the chloroform
      extract of antlers of Cervus nippon, guided by the hematopoietic stimulation of
      stem cells. The structures of monoacetyldiglycerides were determined by various
      spectroscopic methods: FAB MS, CID tandem MS, and 1D and 2D NMR. A mixture of at
      least nine inseparable sn-3-monoacetyldiglycerides was identified: 1
      [C(39)H(72)O(6) (C16 : 0/C18 : 1)], 2 [C(39)H(72)O(6) (C18 : 1/C16 : 0)], 3
      [C(39)H(70)O(6) (C16 : 0/C18 : 2)], 4 [C(39)H(70)O(6) (C18 : 2/C16 : 0)], 5
      [C(41)H(74)O(6) (C18 : 0/C18 : 2), 6 [C(41)H(74)O(6) (C18 : 2/C18 : 0)], 7
      [C(41)H(74)O(6) (C18 : 1/C18 : 1)], 8 [C(43)H(74)O(6) (C18 : 0/C20 : 4)], and 9
      [C(43)H(74)O(6) (C20 : 4/C18 : 0)]. Among these nine monoacetyldiglycerides in
      deer antlers, compound 3 was one of the major compounds and was efficiently
      synthesized from glycerol. Spectral data of synthetic monoacetyldiglyceride 3
      were compared with the corresponding data for the mixture of natural
      monoacetyldiglycerides. The mixture of natural monoacetyldiglycerides from deer
      antlers showed potent activity on the hematopoiesis (stimulation index=1.40+/
      0.05, p<0.02 at 1 microg/ml), and synthetic monoacetyldiglyceride 3 showed even
      better activity (stimulation index=1.54+/-0.12, p<0.001, at 1 microg/ml).

PMID- 15256715
TI  - Four ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep.
AB  - From the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis
      GAGNEP. (Euphorbiaceae) the four new ent-kaurane-type diterpenoids ent
      1alpha,14alpha-diacetoxy-7beta-hydroxykaur-16-en-15-one (1), ent-1alpha,7beta
      diacetoxy-14alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-14alpha
      hydroxykaur-16-en-15-one (3), and ent-(16S)-18-acetoxy-7beta-hydroxykauran-15-one
      (4) were isolated. Their structures were elucidated by spectroscopic analyses.

PMID- 15256716
TI  - New sesquiterpenoid and triterpenoids from the fruits of Rhizophora mucronata.
AB  - A new sesquiterpene (1) and two new pentacyclic triterpenoid esters (2, 3)
      together with three known compounds (4-6) were isolated from the fruits of
      Rhizophora mucronata. Their structures were elucidated by analysis of their
      spectroscopic data. The new compounds were characterized as 3-hydroxy-3,7,11
      trimethyl-9-oxododeca-1,10-diene (mucronatone, 1), 3beta-E-caffeoyltaraxerol (2)
      and 3beta-Z-caffeoyltaraxerol (3).

PMID- 15256717
TI  - Three novel crustulinol esters, saponaceols A-C, from Tricholoma saponaceum.
AB  - Three novel triterpene esters, saponaceols A (1), B (2), and C (3) were isolated
      from the fruiting body of the fungus Tricholoma saponaceum, and their structures
      were elucidated on the basis of extensive NMR experiments. Saponaceol A (1)
      exhibited moderate inhibitory activity against HL-60 cells.

PMID- 15256718
TI  - Pharmacogenomics of drug transporters: a new approach to functional analysis of
      the genetic polymorphisms of ABCB1 (P-glycoprotein/MDR1).
AB  - In the 21st century, emerging genomic technologies (i.e., bioinformatics,
      functional genomics, and pharmacogenomics) are shifting the paradigm of drug
      discovery research and improving the strategy of medical care for patients. In
      order to realize the personalized medicine, it is critically important to
      understand molecular mechanisms underlying inter-individual differences in the
      drug response, namely, pharmacological effect vs. side effect. Evidence is now
      accumulating to strongly suggest that drug transporters are one of the
      determinant factors governing the pharmacokinetic profile of drugs. Effort has
      been made to identify genetic variation in drug transporter genes. In particular,
      genetic variations of the human ABCB1 (P-glycoprotein/MDR1) gene have been most
      extensively studied. Hitherto more than fifty single nucleotide polymorphisms
      (SNPs) and insertion/deletion polymorphisms in the ABCB1 gene have been reported.
      However, at the present time, information is still limited with respect to the
      actual effect of those genetic polymorphisms on the function of ABCB1. In this
      context, we have undertaken functional analyses of ABCB1 polymorphisms. To
      quantify the impact of genetic polymorphisms on the substrate specificity of
      ABCB1, we have developed a high-speed screening system and a new structure
      activity relationship (SAR) analysis method. This review addresses functional
      aspects of the genetic polymorphism of ABCB1 and provides the standard method to
      evaluate the effect of polymorphisms on the function.

PMID- 15256720
TI  - Cell death mode switch from necrosis to apoptosis in brain.
AB  - In brain ischemia, cell destructive necrosis occurs in the core, which in turn
      links to cell death expansion in the vicinity. Apoptosis, on the other hand,
      occurs in the surroundings of the core, called the penumbra, several days later.
      As cells showing apoptosis disappear by microglial phagocytosis in the brain,
      cell death induced by ischemic stress should eventually be terminated. Thus, the
      authors propose the hypothesis that the cell death mode switch in the event of
      brain ischemia is an in vivo self-protective mechanism. The authors attempt to
      overview the current understanding of the molecular mechanisms of necrosis and
      apoptosis in relation to the ATP hypothesis, and also introduce novel mechanisms
      for an in vitro cell death mode switch.

PMID- 15256721
TI  - Role of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx)
      as an antiapoptotic factor.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique antioxidant
      enzyme that markedly reduces lipid hydroperoxide generated in biomembranes.
      Overexpression of mitochondrial PHGPx potentially suppresses the release of
      cytochrome c (cyt. c) from mitochondria and apoptosis. The hydroperoxide level in
      mitochondria was elevated in 2-deoxyglucose (2DG)-induced apoptosis, but not in
      apoptosis-resistant cells in which mitochondrial PHGPx was overexpressed. From
      studies of the overexpression of PHGPx, the generation of hydrogen peroxide and
      lipid hydroperoxide in mitochondria might be important triggers of apoptosis. In
      particular lipid hydroperoxide could be involved in the initiation of cyt. c
      liberation from mitochondria in 2DG-induced apoptosis since lipid hydroperoxide
      is a primary substrate for PHGPx. The release of cyt. c from mitochondria is an
      important proapoptotic signal in the mitochondrial death pathway. Several reports
      demonstrated the reactive oxgen species could be involved in cyt. c liberation,
      although its mechanism is still unknown. Cardiolipin (CL), which exclusively
      locates in the innermembrane of mitochondria, shows strong affinity for cyt. c is
      required for the adenine nucleotide translocator (ANT) that controls the opening
      and closing of the permeability transition pore. Association of cyt. c with CL is
      lost upon peroxidation. CL hydroperoxide (CLOOH), in contrast to CL, does not
      bind to cyt. c. Furthermore, CLOOH can open the permeability transion pore by the
      inactivation of ANT. These previous results suggest that mitochondrial PHGPx
      inhibits the release of cyt. c from mitochondria by the scavenging CLOOH and
      could prevent apoptosis.

PMID- 15256722
TI  - Neuronal apoptosis and protection: effects of nitric oxide and endoplasmic
      reticulum-related proteins.
AB  - This review presents recent findings with regard to the cellular and molecular
      mechanisms of neuronal apoptosis induced by cerebral ischemia/hypoxia. The
      protection of neuronal death by hypoxia-induced proteins in the endoplasmic
      reticulum (ER) is also reviewed. The excess amount of nitric oxide (NO) generated
      by inducible NO synthase (iNOS) up-regulated in response to ischemic stress
      causes neuronal apoptosis through following processes; 1) reduction in
      mitochondrial membrane potential, 2) release of cytochrome c from mitochondria,
      and 3) activation of caspase-9 and -3, although low concentrations of NO protect
      against neuronal death. In contrast, hypoxia induces expression of several
      proteins such as protein disulfide isomerase (PDI), ubiquilin and HRD1 in the
      endoplasmic reticulum (ER). PDI and ubiquilin are involved in the protection
      against neuronal apoptosis probably by interacting with each other and enhancing
      the effects of PDI as a molecular chaperon. HRD1 is also up-regulated by hypoxia
      in the ER and induces protection against hypoxia-induced neuronal apoptosis by
      activating the protein degradation system. The present review hopefully gives
      pertinent suggestions for further studies on the development of novel
      prophylactic/therapeutics for neuronal apoptosis-related diseases.

PMID- 15256723
TI  - Endogenous factors regulating neuronal death induced by radical stress.
AB  - Neurons in the central nervous system (CNS) are vulnerable to radical stress
      caused by reactive oxygen species, including nitric oxide (NO). Those radicals
      play crucial roles in glutamate neurotoxicity associated with ischemic brain
      injury and a wide range of neurodegenerative disorders. In our previous studies,
      we have shown evidence suggesting that glutamate neurotoxicity is regulated by
      certain endogenous substances such as neurotrophins, nicotinic acetylcholine,
      prostanoids and vitamins. Based on those findings, we have used the term
      'neuroprotective factor' for endogenous substances possessing protective activity
      against glutamate neurotoxicity, and have further searched for a candidate with
      unique structure. We isolated a novel neuroprotective substance named 'serofendic
      acid' derived from fetal calf serum. The compound exhibited potent protective
      action against neurotoxicity induced by glutamate and by an NO donor without
      inhibiting glutamate receptors. Electron spin resonance analysis demonstrated
      that serofendic acid had no direct scavenging activity on NO, but was capable of
      inhibiting the generation of a hydroxyl radical, a presumed 'executor' radical in
      the nitric oxide-mediated neurotoxic cascade. The chemical structure was
      determined by mass spectrometry and nuclear magnetic resonance spectroscopy, and
      was confirmed by synthesis. The structure was unique among known endogenous
      substances because the compound was a sulfur-containing atisane type diterpenoid.
      The discovery of serofendic acid may provide a new scope for the investigation of
      low-molecular weight bioactive factors promoting the survival of CNS neurons.

PMID- 15256724
TI  - Genomic drug discovery for apoptosis regulation using a new computer screening
      amino acid complement wave method.
AB  - A novel caspase-3-specific inhibitory peptide and an agonistic peptide that binds
      to the Fas molecule were discovered using our computer screening strategy called
      the amino acid complement wave (ACW) method, which is based on the
      complementarities of interacting amino acids between comprehensive testing
      peptides and a target protein surface pocket. The precise binding configurations
      of the designed peptides on the three-dimensional (3D) structure of the target
      protein and the prediction of binding affinities (DeltaG) are determined by the
      molecular docking program. A designed novel tetrapeptide inhibitor of caspase-3,
      Ac-DNLD-CHO, was revealed to have potent and specific inhibitory activity. When a
      designed Fas ligand mimic peptide (Fas reactive peptide-4, FRAP-4) was
      multimerized by carboxyl terminal linkages of polylysine branches (MAP), the
      octamer (FRAP-4)(8)-MAP effectively induced apoptosis of human ovarian cancer
      cell line NOS4 cells. Thus the ACW method for structure-based design of optimized
      small peptides can be used to further develop small peptidomimetic and
      nonpeptidic organic forms into a new generation of effective pharmaceuticals.

PMID- 15256725
TI  - Screening of furanocoumarin derivatives in citrus fruits by enzyme-linked
      immunosorbent assay.
AB  - This paper reports a sensitive and specific enzyme-linked immunosorbent assay for
      screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in
      citrus fruits. Anti-6',7'-dihydroxybergamottin antibody was obtained by
      immunizing rabbits with 6',7'-dihydroxybergamottin conjugated with bovine serum
      albumin using the N-succinimidyl ester method. An enzyme marker was similarly
      prepared by coupling 6',7'-dihydroxybergamottin with beta-D-galactosidase. The
      enzyme-linked immunosorbent assay is capable of detecting as little as 800 pg/ml
      of 6',7'-dihydroxybergamottin and 4 ng/ml of bergamottin. Cross-reactivity data
      showed that the antibody well recognizes both the furanocoumarin and 6,7
      dihydroxy-3,7-dimethyloct-2-enyloxy moieties of the 6',7'-dihydroxybergamottin,
      and is thus specific to the structure of furanocoumarin derivatives containing
      geranyloxy side chain as the cytochrome P450 3A4 inhibitors in grapefruit juice.
      The antibody was, therefore, used for screening a large number of citrus fruits
      for furanocoumarin derivatives such as 6',7'-dihydroxybergamottin. Fifteen citrus
      fruits were examined and significant reactivity was observed in 8 of these: red
      pummelo, sweetie, melogold, banpeiyu pummelo, hassaku, sour orange, lime and
      natsudaidai. This enzyme-linked immunosorbent assay may be a powerful tool for
      screening for furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in
      grapefruit juice.

PMID- 15256726
TI  - The feeding of beta-carotene down-regulates serum IgE levels and inhibits the
      type I allergic response in mice.
AB  - Feed containing beta-carotene was administered orally to BALB/c mice immunized
      intraperitoneally with ovalbumin (OVA) for approximately 1 month. The titers of
      OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in the mouse sera were
      determined. The OVA-specific IgE titer and OVA-specific IgG1 titer by mice fed
      beta-carotene were significantly inhibited. On the other hand, the OVA-specific
      IgG2a titer in mice fed beta-carotene was significantly greater than those of
      control mice. The OVA-specific IgE suppression of beta-carotene feeding was dose
      dependent. We also examined the effect of fed beta-carotene on active systemic
      anaphylaxis. Feeding beta-carotene to mice immunized with OVA inhibited the
      immediate reduction of the body temperature induced by antigen stimulation.
      Furthermore, the increase in serum histamine in the mice fed beta-carotene under
      active systemic anaphylaxis was lower than in controls. We then examined the
      pattern of cytokine production by spleen cells from mice followed by
      restimulation with OVA in vitro. The spleen cells from the mice fed beta-carotene
      produced more IFN-gamma, IL-12 and IL-2 than those from the control group. In
      contrast, the spleen cells from the mice fed beta-carotene produced less IL-4, IL
      5, IL-6, IL-10 than those from the control group. Furthermore, analysis of IFN
      gamma mRNA levels of the splenocytes using the real-time quantitative RT-PCR
      technique revealed higher levels in the splenocytes from the mice fed beta
      carotene. These findings suggest that feeding beta-carotene improves the helper T
      cell (T(H))1-T(H)2 balance, inhibiting specific IgE and IgG1 production and
      antigen-induced anaphylactic response.

PMID- 15256727
TI  - Enhanced release of prostaglandin D2 during re-incubation of RAW 264.7 macrophage
      like cells after treatment of both lipopolysaccharide and non-steroidal anti
      inflammatory drugs.
AB  - RAW 264.7 macrophage-like cells are known to release prostaglandins (PGs), mainly
      PGD(2) to the culture medium after lipopolysaccharide (LPS)-treatment. This
      release was inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), which
      are known to inhibit prostaglandin H(2) synthase (PGHS) activity. In this study,
      we examined the effect of removal of NSAID after induction of PGHS with LPS, on
      the release of PGs, which has not been studied well. Re-incubation of RAW 264.7
      cells after treatment of both LPS and NSAIDs resulted in enhanced release of
      PGD(2) compared with the cells pretreated with LPS alone. Besides, PGHS activity
      was detectable in these cell homogenates and the amount of PGHS-2 protein showed
      similar changes to PGD(2) release. However, addition of NSAIDs again in the re
      incubation period almost completely inhibited the PGD(2) release but increased
      the amount of PGHS-2 protein to the higher levels. Various types of NSAIDs used
      in this study showed similar effects on the changes in PGD(2) release and PGHS-2
      protein amounts, except those on PGHS activity in cell homogenates; while
      indomethacin, aspirin, and NS-398 inhibited it, but nimesulide and acetaminophen
      did not. These results seem to suggest an importance for the caution that the
      enhanced induction of PGHS-2 protein and the concomitant release of PGs release
      would occur after removal of the NSAID not only from the medium in in vitro
      experiments but also from therapeutic prescription.

PMID- 15256728
TI  - Implication of CDK inhibitors p21 and p27 in the differentiation of HL-60 cells.
AB  - All-trans retinoic acid (ATRA) differentiates HL-60 cells into granulocyte-like
      cells and cellular proliferation is repressed markedly along with the
      morphological and physiological changes specific for cellular differentiation. To
      elucidate the implication of cyclin-dependent kinase (CDK) inhibitors during
      differentiation, we examined the expression of CDK inhibitors during the
      differentiation of HL-60 cells. The expression of p21 and p27 among the CDK
      inhibitors we examined increased during the differentiation induced with ATRA.
      Then, we established stable transformants of HL-60 cells expressing antisense RNA
      for p21 and p27 and examined the ability of these cells to differentiate into
      granulocyte-like cells. The extents of fully differentiated HL-60 cells
      transfected with genes for antisense RNA of p21 and p27 were only 53% and 60%,
      respectively, whereas 90% of the parental HL-60 cells differentiated by the ATRA
      treatment. These results suggest that increased expression of CDK inhibitors, p21
      and p27, is necessary for the differentiation of HL-60 cells induced with ATRA.

PMID- 15256729
TI  - Gambogic acid induces apoptosis and regulates expressions of Bax and Bcl-2
      protein in human gastric carcinoma MGC-803 cells.
AB  - The selective induction of apoptosis of gambogic acid (GA) on MGC-803 cells and
      its probable molecular mechanism were studied. GA greatly inhibited (24, 48, 72
      h) the growth of MGC-803 cells (by MTT); the IC(50) value was 0.96 microg/ml at
      48 h. Meanwhile, no influence was observed on body weight, number of WBC (white
      blood cells) in blood or karyote in marrow of rats after GA was injected
      intravenously. We conclude that GA does not affect normal cells, but that it can
      induce apoptosis in tumor cells selectively and there were marked morphological
      changes. A great quantity of apoptotic cells and increasing G(2)/M phase cells
      were observed by flow cytometry, and a significant percentage of early apoptotic
      cells were observed by Annexin-V/PI double staining assay. The increase of bax
      gene and the decrease of bc1-2 gene expressions were detected by
      immunohistochemistry. Activation of bax and suppression of bc1-2 may contribute
      to the apoptosis mechanism.

PMID- 15256730
TI  - Antioxidant and immuno-enhancing effects of Echinacea purpurea.
AB  - We studied the protective effects of Echinacea purpurea against radiation by
      evaluating changes in the peripheral blood cell count and peripheral blood
      antioxidant activity. E. purpurea administration had a suppressive effect on
      radiation-induced leukopenia, especially on lymphocytes and monocytes, and
      resulted in a faster recovery of blood cell counts. Mouse peripheral blood
      antioxidant activity was increased by E. purpurea, and a relationship between the
      suppressive effect on radiation-induced leukopenia and the antioxidant effect was
      suggested. Furthermore, we reviewed the evidence of augmentation of found in this
      study humoral immunity. The effects of immune activation by E. purpurea were
      investigated by measuring total immunoglobulin (IgG, IgM). The radioprotective
      effects of immune activation by E. purpurea were investigated by measuring T
      lymphocyte subsets in the peripheral blood of mice following whole-body
      irradiation. E. purpurea activates macrophages to stimulate IFN-gamma production
      in association with the secondary activation of T lymphocytes, resulting in a
      decrease in IgG and IgM production. Cytokines released from macrophages in mouse
      peripheral blood after E. purpurea administration activated helper T cells to
      proliferate. In addition, it is reported that activated macrophages in
      association with the secondary T lymphocyte activation increases IFN-gamma
      production and stimulates proliferation of cytotoxic T cells and suppressor T
      cells. We think that CD 4 and CD 8 subsets were more immunologically enhanced by
      E. purpurea than helper T cells and suppressor T cell these results reflect
      activation. In addition, we think that these results reflect cell-mediated immune
      responses.

PMID- 15256731
TI  - The diverse effects of a Chinese medicine, Qing Nao Yi Zhi Fang, on the
      proliferation of human arterial smooth muscle cells and endothelial cells.
AB  - Qing Nao Yi Zhi Fang (QNYZ), a Chinese medicine, has been developed as a drug for
      the prevention and treatment of vascular dementia. We examined the effects of
      QNYZ-treated serum and QNYZ on the proliferation of human arterial smooth muscle
      cells (SMCs) and endothelial cells (ECs). SMCs did not grow in a medium
      containing 10% QNYZ serum. QNYZ also completely inhibited the proliferation of
      SMCs at higher concentrations (500-1000 microg/ml), although no detectable
      inhibitory activity on the SMC proliferation was observed at lower concentrations
      (100-200 microg/ml). In contrast, QNYZ (250-500 microg/ml) significantly
      stimulated the proliferation of ECs and prostacyclin production in ECs. These
      results suggest that QNYZ may have suppressive effects on the development of
      intimal thickening in atherosclerosis and after arterial wall injury.

PMID- 15256732
TI  - Effects of iridoid total glycoside from Cornus officinalis on prevention of
      glomerular overexpression of transforming growth factor beta 1 and matrixes in an
      experimental diabetes model.
AB  - The present study was conducted to determine whether iridoid total glycoside from
      Cornus officinalis was effective in regulating expression of transforming growth
      factor beta 1 (TGF-beta1) and preventing overdeposition of extracellular matrix
      (ECM) in a diabetes state. An experimental rat model of diabetic nephropathy (DN)
      was successfully induced by one intraperitoneal injection of streptozotocin at a
      dose of 60 mg x kg(-1) and maintained for 12 weeks. All rats had free access to
      standard chow and water. Four groups: normal control, diabetic control, diabetic
      rats with aminoguanidine treatment and diabetic rats with iridoid total glycoside
      treatment were used in this experiment. All treatments were administered by
      intragastric gavage (ig). At the end of the experiment, serum was collected for
      ELISA determination of TGF-beta1 protein level; renal cortex was dissected for
      reverse transcription polymerase chain reaction (RT-PCR) analysis of its mRNA
      expression; and immunohistochemistry was introduced to observe ECM deposition. A
      significantly higher level of protein and mRNA expression of TGF-beta1, and also
      overdeposition of fibronectin and laminin was found in diabetic rats. Both
      iridoid total glycoside and aminoguanidine were effective in decreasing serum
      protein level and glomerular mRNA expression of TGF-beta1, and in preventing
      renal overdeposition of fibronectin and laminin. This study suggests that iridoid
      total glycoside is a beneficial agent for prevention and therapy of DN.

PMID- 15256733
TI  - Effects of the new ethacrynic acid derivative SA9000 on intraocular pressure in
      cats and monkeys.
AB  - To evaluate the pharmacological characteristics of the new ethacrynic acid (ECA)
      derivative SA9000, we examined its ocular hypotensive effects in cats and
      cynomolgus monkeys, its corneal toxicity in rabbits, and its binding affinities
      for forty-three receptors, ion channels, and second messenger systems. A 20
      microl injection into the anterior chamber of eye (intracameral injection) of 0.1
      mM SA9000 significantly reduced intraocular pressure (IOP) 3.8 mmHg in cats. A 10
      microl intracameral injection of 1 mM SA9000 significantly reduced IOP 7 mmHg in
      living monkeys without evidence of in vivo (or in vitro) toxicity. The ocular
      hypotensive effect of SA9000 in monkeys was greater than that of ECA. The
      morphology of corneal endothelial and epithelial cells in rabbit eyes after
      intracameral injection of SA9000 was observed using electron microphotography.
      SA9000 at 2 mM did not induce any abnormalities, indicating that it has no
      corneal toxicity at a concentration higher than the minimum needed for an ocular
      hypotensive effect (1 mM). SA9000 at 0.01 mM showed negligible binding affinity
      for, or inhibition of, forty-three different receptors, ion channel proteins, and
      second messenger systems. These findings indicate that SA9000 has the potential
      to be both effective and safe as an ocular hypotensive drug, although the
      mechanism of action remains unclear.

PMID- 15256734
TI  - Cytotoxic effects of mansonone E and F isolated from Ulmus pumila.
AB  - Two sesquiterpenoids, mansonone E (ME) and mansonone F (MF) were first isolated
      from the dried root bark of Ulmus pumila (shironire in Japanese), and their
      antiproliferative activities on human tumor cells were evaluated in vitro. ME had
      more potent cytotoxic effects on four tumor cell lines, human cervical cancer
      HeLa, human malignant melanoma A375-S2, human breast cancer MCF-7, and human
      histiocytic lymphoma U937, than those of MF. The results showed that ME induced
      oligonucleosomal fragmentation of DNA in HeLa cells and activated caspase-3,
      followed by the degradation of the inhibitor of caspase-activated DNase,
      decreased the expression of anti-apoptotic mitochondrial proteins Bcl-2 and Bcl
      (XL), and increased that of proapoptotic Bax.

PMID- 15256735
TI  - Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis.
AB  - Silymarin, a plant flavonoid from milk thistle (Silybum marianum [L.] GAERTNER)
      was first evaluated for its protective effect against UV irradiation-induced
      apoptosis in human malignant melanoma cells (A375-S2 cells). Treatment with
      silymarin 500 microM for 12 h significantly inhibited UV irradiation (2.4
      J/cm(2), 5 min)-induced apoptosis in A375-S2 cells. Activities of caspase-9 and
      caspase-3 in UV-irradiated A375-S2 cells were effectively reduced by silymarin in
      a dose-dependent manner, while the expression of the inhibitor of caspase
      activated DNase (ICAD), protein expression of Bcl-x(L) (Bcl-2 family member), and
      the activity of extracellular signal-regulated kinase/mitogen-activated protein
      kinase (ERK/MAPK) were increased simultaneously. It is suggested that the
      inhibitory effect of silymarin is exerted by blockage of the caspase/ICAD pathway
      after increased expression of Bcl-x(L) protein and activation of the ERK/MAPK
      pathway.

PMID- 15256736
TI  - Preventive effects of Laminaria japonica aqueous extract on the oxidative stress
      and xanthine oxidase activity in streptozotocin-induced diabetic rat liver.
AB  - Increasing evidence in both experimental and clinical studies suggests that
      oxidative stress plays a major role in the pathogenesis of diabetes mellitus type
      1 and type 2. Xanthine oxidase (XO) has been proposed as one of the sources of
      free radical formation in diabetes. We therefore investigated the preventive
      effects of Laminaria japonica aqueous extract (LJE) on alterations in the
      activity of hepatic XO and oxidative stress in the streptozotocin-induced
      experimental diabetes. We found that lipid peroxide levels and xanthine oxidase
      activity were increased, whereas glutathione (GSH), GSH reductase and GSH
      peroxidase were decreased in the liver of streptozotocin-induced diabetic rats.
      Pretreatment with LJE of 100 mg/kg orally for 5 d significantly reduced blood
      glucose levels and hepatic lipid peroxidation in the diabetic rats. In addition,
      the content of glutathione was restored to the control level by LJE pretreatment.
      Furthermore, LJE significantly suppressed the increased activity of XO and type
      conversion of the xanthine dehydrogenase to XO in diabetic rat liver. The results
      suggest that Laminaria japonica would be of great value in preventing
      hyperglycemia in diabetes mellitus as a dietary supplement possibly, through its
      antioxidant activity.

PMID- 15256737
TI  - Effects of pre-germinated brown rice on beta-amyloid protein-induced learning and
      memory deficits in mice.
AB  - We evaluated the effects of pre-germinated brown rice (hatsuga genmai, PGR) on
      learning and memory and compared them with those of polished rice or cornstarch.
      In mice that were fed pellets of polished rice or PGR for two weeks, the learning
      ability in the Morris water maze test was significantly enhanced compared with
      mice that were fed cornstarch pellets. In the Y-maze test, the intake of food
      pellets for two weeks failed to affect spontaneous alternation behavior. Beta
      amyloid(25-35) (Abeta(25-35): 3 nmol/mouse, i.c.v.) protein impaired spontaneous
      alternation behavior in mice that were fed pellets of cornstarch or polished
      rice. In contrast, PGR pellets prevented the Abeta(25-35)-induced impairment of
      spontaneous alternation behavior. These results suggest that polished rice and
      PGR have facilitating effects on spatial learning. In particular, it is surmised
      that PGR may prevent Alzheimer's disease associated with Abeta.

PMID- 15256738
TI  - Wood creosote inhibits calcium mobilization in Guinea pig colonic smooth muscle.
AB  - Wood creosote, a mixture of simple phenolic compounds, has long been used as an
      herbal antidiarrheal medicine. Previous studies have shown that wood creosote has
      antimotility activity on the gastrointestinal (GI) tract, although its mechanism
      of action is not completely understood. The in vitro efficacy of wood creosote on
      calcium mobilization in guinea pig colonic smooth muscle was evaluated using a
      digital video camera system mounted on an inverted fluorescence microscope. The
      effects of wood creosote on spontaneous periodic increases in the free cytosolic
      calcium concentration ([Ca(2+)](i)), acetylcholine (ACh)-enhanced periodic
      increases in [Ca(2+)](i), and tetrodotoxin- or nifedipine-resistant spontaneous
      periodic increases in [Ca(2+)](i) were evaluated. Wood creosote decreased the
      amplitude of spontaneous (IC(50)=21 microg/ml) and ACh-enhanced (IC(50)=40
      microg/ml) periodic increases in [Ca(2+)](i) in guinea pig colonic smooth muscle.
      Wood creosote also decreased the amplitude of both tetrodotoxin- and nifedipine
      resistant spontaneous periodic increases in [Ca(2+)](i). These results suggest
      that antimotility activity through inhibition of Ca(2+) mobilization in the GI
      tract is at least partially responsible for the antidiarrheal activity of wood
      creosote. Wood creosote may exert its antimotility effect, at least in part, on
      network regions of interstitial cells of Cajal, which act as pacemaker cells and
      mediators of neurotransmission in the GI tract.

PMID- 15256739
TI  - Partial involvement of group I metabotropic glutamate receptors in the
      neurotoxicity of 3-N-oxalyl-L-2,3-diaminopropanoic acid (L-beta-ODAP).
AB  - Neurolathyrism is a human motoneuron disease caused by the overconsumption of
      grass pea (Lathyrus sativus) that contains a toxic non-protein amino acid, 3-N
      oxalyl-L-2,3-diaminopropanoic acid (L-beta-ODAP). The preventive activities of
      various glutamatergic agents from acute neuronal death caused by L-beta-ODAP were
      studied using rat primary cortical neuron/glia culture. Nearly 80% of the rat
      primary cortical neurons were killed by 300 microM L-beta-ODAP within 24 h.
      Though antagonists acting on the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor prevented most of the toxicity,
      antagonists acting on group I metabotropic glutamatergic receptors (mGluRs),
      including (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), (S)-alpha-methyl-4
      carboxyphenylglycine (MCPG), and 2-methyl-6-(2-phenylethenyl)pyridine (SIB1893)
      partially and significantly prevented neuronal death due to L-beta-ODAP. These
      antagonists, within limited concentrations, did not have any inhibitory effects
      on the currents through AMPA receptors expressed in Xenopus oocytes. L-beta-ODAP
      itself did not induce the currents through group I mGluRs expressed in Xenopus
      oocytes. These results suggest that the neurotoxicity induced by L-beta-ODAP is
      partially mediated by the activation of group I mGluRs by an indirect mechanisms.

PMID- 15256740
TI  - The mitotic-arresting and apoptosis-inducing effects of diosgenyl saponins on
      human leukemia cell lines.
AB  - Diosgenyl saponins are the most abundant steroid saponins, and exert a large
      variety of biological functions. In a previous report, we showed that dioscin was
      able to induce cytotoxicity and apoptosis in human myeloblast leukemia HL-60
      cells. This study further investigated the action mechanisms underlying this
      effect. The activation of caspase-9 and -3, but not caspase-8, together with the
      down-regulation of anti-apoptotic Bcl-2 protein, demonstrated that the apoptotic
      signaling triggered by dioscin was mediated through the intrinsic mitochondria
      dependent pathway. We also investigated its anti-proliferative effect on human
      chronic myelogenous leukemia K562 cells. Flow cytometry analysis showed that
      dioscin treatment induced the accumulation of cells in the G(2)/M phase.
      Cytomorphology with DAPI and Wright-Giemsa staining demonstrated the enlargement
      of cell volume and multinucleation in the treated cells. Subsequent apoptosis was
      delineated with phosphatidylserine externalization and DNA hypodiploidy. Trillin
      was one of the hydrolysates of dioscin. We demonstrated that it could induce
      multinucleation in HL-60, K562 and human promyelocytic leukemia NB(4) cells,
      suggesting its extensive mitotic-arresting effects. As the diosgenyl sapogenin,
      diosgenin was also shown to be able to induce multinucleation and apoptosis in
      K562 cells in a similar manner to dioscin. These findings suggest that diosgenyl
      saponins have the properties to induce mitotic arrest and apoptosis, suggesting
      that they may be a new kind of antimitotic agent.

PMID- 15256741
TI  - Extracts from Schizandra chinensis fruit activate estrogen receptors: a possible
      clue to its effects on nitric oxide-mediated vasorelaxation.
AB  - Schizandra chinensis fruit has long been used for the treatment of cardiovascular
      symptoms associated especially with menopausal symptoms in Korea. To provide a
      scientific rationale for such uses, we have investigated the vasorelaxant effects
      of Schizandra chinensis fruit on the vasomotor tone of the rat thoracic aorta in
      an organ bath. The crude extracts of Schizandra chinensis fruit (SC-Ex) elicited
      a transient relaxing response in the endothelium-intact rat aorta contracted with
      norepinephrine. This relaxant effect was abolished by removal of the endothelium,
      and also by pretreatment with nitric oxide synthase inhibitor. We then examined
      whether this vasodilatory effect occurs through estrogen receptor by reporter
      assays. SC-Ex activated the estrogen-responsive luciferase gene in COS cells
      transiently transfected with estrogen receptor and reporter plasmids. The
      activation was maintained in the butanol-soluble fraction and further increased
      in the successively fractionated C(18) cartridge-adsorbed fraction (SC-ADF).
      Reporter gene activation by SC-ADF was inhibited by the specific estrogen
      receptor antagonist ICI 182,780, indicating that the effect is estrogen receptor
      dependent. However, SC-ADF failed to activate the androgen receptor in COS cells
      transfected with the corresponding receptor and reporter plasmids. These data
      show that extracts of Schizandra chinensis fruit act as a weak phytoestrogen.

PMID- 15256742
TI  - Antiproliferative activity of Rhinacanthus nasutus (L.) Kurz extracts and the
      active moiety, Rhinacanthin C.
AB  - Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is a shrub widely distributed in
      South China and India. In this study, the antiproliferative activity of the
      ethanol extract of root and aqueous extract of leaves of R. nasutus, and the
      supposed active moiety rhinacanthin C was assessed in vitro using the human
      cervical carcinoma cell line HeLa, its MDR1-overexpressing subline Hvr100-6,
      human prostate carcinoma PC-3 cells and human bladder carcinoma T24 cells.
      Rhinacanthin C was chemically synthesized and its content in the R. nasutus
      extracts was determined by HPLC with a photodiode array detector. The
      antiproliferative activity of the R. nasutus extracts was also assessed in vivo
      using sarcoma 180-bearing mice. It was suggested that 1) the in vitro
      antiproliferative activity of rhinacanthin C was comparable with or slightly
      weaker than that of 5-FU, 2) rhinacanthin C showed antiproliferative activity for
      MDR1-overexpressing Hvr100-6 cells, similarly to parent HeLa cells, 3) the in
      vitro antiproliferative activity of the ethanol extract of root R. nasutus was
      due to rhinacanthin C, whereas that of the aqueous extract of leaves of R.
      nasutus was due to constituents other than rhinacanthin C, and 4) both of the R.
      nasutus extracts showed in vivo antiproliferative activity after oral
      administration once daily for 14 d.

PMID- 15256743
TI  - Dual effects of cycloheximide on U937 apoptosis induced by its combination with
      VP-16.
AB  - In this study, cycloheximide (CHX) and VP-16 alone and in combination (C&V) have
      been used to strongly trigger apoptosis in U937 cells. The presence of CHX
      markedly prevented VP-16-induced apoptosis, suggesting that in this process de
      novo protein synthesis is required. But interestingly, C&V had shown more
      similarities with CHX but not VP-16 alone, including the effects on cell cycle
      distribution and induction of apoptosis, which occurred more quickly and was
      steadily enhanced by increasing concentrations of CHX or by N-alpha-tosyl-L-lysyl
      chloromethyl ketone (TLCK), a serine protease inhibitor. These results indicate
      that CHX, not VP-16, is indeed the dominant inducer of U937 apoptosis, when they
      are coadministered. In particular, VP-16 even promoted CHX-induced apoptosis, but
      did not alter its selection of cell types. In T-cells resistant to CHX (Molt-4),
      we have detected no apoptotic response to their combination. These findings may
      well explain why the inhibitory effects of CHX on apoptosis induced by the same
      stimuli are usually different according to the cell type used, and also suggest
      that CHX may have the potential to lower side effects and drug resistance of
      cancer therapy.

PMID- 15256744
TI  - Cognitive improving and cerebral protective effects of acylated oligosaccharides
      in Polygala tenuifolia.
AB  - We studied the cognitive improving and cerebral protective constituents in the
      roots of Polygala tenuifolia Willdenow, a well-known Chinese traditional medicine
      prescribed for amnesia, neurasthenia, palpitation, noctural emission and
      insomnia. Tenuifoliside B (1), which is one of the acylated oligosaccharides in
      the roots of P. tenuifolia, showed the cerebral protective effect on potassium
      cyanide (KCN)-induced anoxia in mice, widely used as an animal model for
      cerebrovascular disease, and also had an ameliorative effect on the scopolamine
      induced impairment of performance in passive avoidance task in rats. Compound 1
      significantly enhanced oxotremorine-induced tremors in mice, suggesting that it
      ameliorated the scopolamine-induced impairment of passive avoidance response by
      enhancing the cholinergic system. These findings show that compound 1 has
      cognitive improving and cerebral protective effects.

PMID- 15256745
TI  - Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza
      glabra.
AB  - The cultured cells and intact plants of Glycyrrhiza glabra (Fabaceae) produce
      betulinic acid and oleanane-type triterpene saponins (soyasaponins and
      glycyrrhizin). To elucidate the regulation of triterpenoid biosynthesis in G.
      glabra, the cDNA of lupeol synthase, an oxidosqualene cyclase (OSC) responsible
      for betulinic acid biosynthesis, was cloned, and expression patterns of lupeol
      synthase and two additional OSCs, beta-amyrin synthase and cycloartenol synthase,
      were compared. The mRNA expression levels of lupeol synthase and beta-amyrin
      synthase were consistent with the accumulation of betulinic acid and oleanane
      type triterpene saponins, respectively. The transcript of lupeol synthase was
      highly expressed in the cultured cells and root nodules. The transcript of beta
      amyrin synthase, an OSC responsible for oleanane-type triterpene biosynthesis,
      was highly expressed in the cultured cells, root nodules and germinating seeds,
      where soyasaponin accumulates, and in the thickened roots where glycyrrhizin
      accumulates. In the cultured cells, the addition of methyl jasmonate up-regulated
      beta-amyrin synthase mRNA and soyasaponin biosynthesis, but down-regulated lupeol
      synthase mRNA. Furthermore, the addition of gibberellin A(3) down-regulated beta
      amyrin synthase mRNA but not lupeol synthase mRNA in the cultured cells. The mRNA
      levels of cycloartenol synthase, an additional OSC responsible for sterol
      biosynthesis, in the intact plant and cultured cells were relatively constant in
      these experiments.

PMID- 15256746
TI  - Effects of oolong tea on plasma antioxidative capacity in mice loaded with
      restraint stress assessed using the oxygen radical absorbance capacity (ORAC)
      assay.
AB  - In the present study, we investigated the antioxidative effect of oolong tea in
      vitro and in vivo using the oxygen radical absorbance capacity (ORAC) assay. An
      oolong tea extract, catechin and related compounds suppressed the oxidation of
      fluorescence induced by AAPH in a dose-dependent manner, that is, they prolonged
      the antioxidant time in vitro. Oral administration of the oolong tea extract to
      mice treated with restraint stress increased ORAC activity in plasma as compared
      with a stress control group. The extract also increased plasma vitamin C levels,
      and there was a good relationship between ORAC activity and the vitamin C level
      in plasma. The elevation of plasma ORAC and vitamin C level may have been related
      to the stress-relieving effect of oolong tea. These effects are probably due to
      the antioxidative properties of the tea. Thus, these findings suggested that
      oolong tea has beneficial effects on health related to its antioxidative action.

PMID- 15256747
TI  - Passive cutaneous anaphylaxis-inhibitory action of tectorigenin, a metabolite of
      tectoridin by intestinal microflora.
AB  - Tectoridin isolated from the flowers of Pueraria thunbergiana (Leguminosae) are
      metabolized to tectorigenin by human intestinal microflora. When tectoridin was
      orally administered to rats, tectorigenin, but not tectoridin, was detected in
      urine after beta-glucuronidase hydrolysis. The main metabolite tectorigenin
      potently inhibited the passive cutaneous anaphylaxis reaction and inhibited in
      vitro the release of beta-hexosaminidase from RBL-2H3 cells induced by IgE. These
      results suggest that tectoridin is a prodrug, which can be transformed into the
      active agent tectorigenin by human intestinal bacteria and can be a candidate for
      antiallergic agent.

PMID- 15256748
TI  - Corosolic acid induces GLUT4 translocation in genetically type 2 diabetic mice.
AB  - The effect of corosolic acid (CA) on blood glucose was studied in KK-Ay mice, an
      animal model of type 2 diabetes. CA (10 mg/kg) reduced the blood glucose (p<0.05)
      of KK-Ay mice 4 h after single oral administration when compared with the control
      group. However, CA did not change the plasma insulin. The muscle facilitative
      glucose transporter isoform 4 (GLUT4) translocation from low-density microsomal
      membrane to plasma membrane was significantly increased in the orally CA-treated
      mice when compared with that of the controls (p<0.05). These results suggest that
      the hypoglycemic effect of CA is derived, at least in part, from an increase in
      GLUT4 translocation in muscle. Therefore, it may be that CA has beneficial
      effects on hyperglycemia in type 2 diabetes.

PMID- 15256749
TI  - Induction of apoptosis by yomogin in human promyelocytic leukemic HL-60 cells.
AB  - Yomogin is an active compound isolated from Artemisia princep, a traditional
      Oriental medicinal herb, which has been shown to inhibit tumor cell
      proliferation. In this study, we investigated the effects of yomogin on the
      cytotoxicity, induction of apoptosis, and putative pathways of its actions in
      human promyelocytic leukemia cells. Yomogin-treated HL-60 cells displayed several
      features of apoptosis, including DNA fragmentation, formation of DNA ladders in
      agarose gel electrophoresis, and externalization of annexin-V targeted
      phosphatidylserine residues. We observed that yomogin caused activation of
      caspase-8, caspase-9, and caspase-3. A general caspase inhibitor (z-VAD-fmk),
      caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk), almost
      completely suppressed the yomogin-induced DNA fragmentation. We further
      demonstrated that yomogin induced Bid cleavage, mitochondrial translocation of
      Bax from the cytosol, and cytochrome c release from mitochondria in a caspase-8
      dependent manner. Taken together, our data indicate that yomogin is a potent
      inducer of apoptosis and facilitates its activity via caspase-8 activation, Bid
      cleavage, Bax translocation to mitochondria, and subsequent release of cytochrome
      c into the cytoplasm, providing a potential mechanism for the anticancer activity
      of yomogin.

PMID- 15256750
TI  - The antiproliferative activity of saponin-enriched fraction from Bupleurum Kaoi
      is through Fas-dependent apoptotic pathway in human non-small cell lung cancer
      A549 cells.
AB  - Bupleuri Radix (Chai-hu in Chinese and Saiko in Japanese) is one of the most
      important traditional Chinese crude drugs for treating hepatitis malaria and
      intermittent fever. B. kaoi is one of the Bupleurum spp. families locally found
      in Taiwan. The effects of saponin-enriched fraction (SEF) from Bupleurum Kaoi in
      human non-small cell lung cancer A549 cells were investigated in this study. An
      enhancement in Fas and its two forms of ligands, membrane-bound Fas ligand
      (mFasL) and soluble Fas ligand (sFasL), was responsible for the apoptotic effect
      induced by SEF. Taken together, our study suggests that the activity of the
      Fas/Fas ligand apoptotic system may participate in the antiproliferative activity
      of SEF in A549 cells.

PMID- 15256751
TI  - Evaluation of synergism between the aminoglycoside antibiotic streptomycin and
      the cardiovascular agent amlodipine.
AB  - Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in
      vitro against 504 bacterial strains belonging to both Gram positive and Gram
      negative genera, as well as in vivo against a mouse-virulent bacterium. Based on
      such findings, the present study was undertaken to determine whether the efficacy
      of this non-antibiotic drug could be enhanced in the presence of any antibiotic.
      Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics,
      viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline,
      erythromycin and ciprofloxacin were chosen. Disc diffusion test with amlodipine
      and streptomycin revealed marked synergism between the combination, compared with
      their individual effects. The synergism was found to be statistically significant
      (p<0.01). To assess the degree of synergy, the checkerboard analysis was
      performed. The fractional inhibitory concentration (FIC) index of this
      combination turned out to be 0.24, which confirmed synergism. This antibiotic-non
      antibiotic pair was then administered to mice, challenged with S. typhimurium to
      determine whether this was effective in vivo. Statistical analysis of the mouse
      protection tests suggested that the combination was highly synergistic (p<0.001),
      according to Student's t-test. This synergistic drug combination may help us in
      enhancing the scope of prolonged antibiotic therapy in various types of
      infections, and might open a new therapeutic approach to combat drug resistance
      in bacterial diseases.

PMID- 15256752
TI  - Stimulatory effects of monoacetyldiglycerides on hematopoiesis.
AB  - Monoacetyldiglycerides purified from deer antler, and identical synthetic
      compounds, have been shown to stimulate hematopoiesis. In the present study, we
      synthesized eight monoacetyldiglycerides, one of which, 1-palmitoyl-2-linoleoyl-3
      acetyl-rac-glycerol (3), was structurally identical to one of the naturally
      occurring monoacetyldiglycerides and showed the most potent stimulation of
      hematopoiesis by colony forming unit in culture (CFUc) assay, having a
      stimulation index (SI) of 1.54+/-0.23 at a concentration of 1.0 microg/ml.
      Moreover, 1.0 microg/ml 3 showed potent growth-stimulation activities on
      megakaryocyte culture, long term culture of Lin(-)Sca-1(+) cells with irradiated
      MS-5 stromal cells (SI, 1.69+/-0.16), and on the number of cobblestone colonies
      (SI, 10.4+/-0.25). In a murine model, 3, at concentrations of 0.5, 5 and 50
      mg/kg/d, i.p. and p.o., effectively stimulated hematopoiesis in vivo 7 d after
      syngenic bone marrow transplantation of irradiated C57BL/6 mice, when assayed by
      the colony forming units in spleen (CFUs) assay. These data suggest that
      monoacetyldiglycerides may have significant clinical potential for the
      acceleration of hematopoiesis.

PMID- 15256753
TI  - Mycelial extract of Cordyceps ophioglossoides prevents neuronal cell death and
      ameliorates beta-amyloid peptide-induced memory deficits in rats.
AB  - Ameliorating effects of methanol extracts of Basidiomycetes against in vitro and
      in vivo model of Alzheimer's disease were investigated. The extracts of Cordyceps
      ophioglossoides and Hypocrea citrina var. citrina prevented the beta-amyloid((25
      35)) (Abeta((25-35)))-induced cell death in SK-N-SH neuronal cells. However, in
      rat model of Alzheimer's disease, 30-d intraperitoneal administration with only
      the extract of Cordyceps ophioglossoides significantly prevented spatial memory
      loss by intracranial injection of Abeta((25-35)), which was assessed in water
      maze task. Interestingly, the scavenging activity of the reactive oxygen species
      (ROS) generated in Abeta((25-35))-treated cells was also found in the extract of
      Cordyceps ophioglossoides, but not in the extract of Hypocrea citrina var.
      citrina. These results suggest that the extract of Cordyceps ophioglossoides may
      protect the Abeta-induced neuronal cell death and memory loss through free
      radical scavenging activity. These results further suggest that Cordyceps
      ophioglossoides mycelium may be valuable for the protection from Alzheimer's
      dementia.

PMID- 15256754
TI  - Impaired gene expression of beta 1-adrenergic receptor, but not stimulatory G
      protein Gs alpha, in rat ventricular myocardium treated with isoproterenol.
AB  - We investigated the gene expression of beta(1)-adrenergic receptor (beta(1)AR)
      and stimulatory G-protein Gsalpha, important signal transduction elements for
      regulating heart rate and contractility, in ventricle after chronic treatment
      with isoproterenol (ISO) in rat. Rats were treated with ISO (4 mg/kg,
      intraperitoneal) twice a day for 4 d. Ventricle weight of the heart and ventricle
      weight/body weight ratio were increased by 23% and 25% compared with control,
      respectively. Positive inotropic responses to ISO in left atrial muscle
      preparations isolated from ISO-treated rats were markedly decreased. Northern
      blot hybridization showed that the mRNA transcript of beta(1)AR was significantly
      decreased in ventricle of ISO-treated rats, whereas Gsalpha mRNA level was
      unchanged. Present results demonstrate that the gene expression of myocardial
      beta(1)AR, but not Gsalpha, was decreased in rat myocardium of ISO-induced
      cardiac hypertrophy, and suggesting that decrease in the gene expression of
      beta(1)AR may be one of the mechanisms responsible for the diminished cardiac
      function.

PMID- 15256755
TI  - Inhibitory effect of Mao-Bushi-Saishin-to on prostaglandin E2 synthesis in C6 rat
      glioma cells.
AB  - Effect of Mao-Bushi-Saishin-to (Ma-Huang-Fu-Zi-Xi-Xin-Tang: MBS) on prostaglandin
      E(2) (PGE(2)) production was investigated using C6 rat glioma cells. Mao or
      Saishin inhibited histamine-induced PGE(2) production while MBS slightly
      decreased and Bushi increased it. MBS and Mao inhibited and Bushi enhanced A23187
      induced PGE(2) production while Saishin had no effect. Concomitantly, Mao
      inhibted, but Bushi fascilitated, histamine- and A23187-induced phosphorylation
      of extracellular signal-regulated kinase (ERK)1/2. Treatment of MBS, Mao and also
      Saishin increased cAMP content. From these results, MBS inhibit PGE(2) production
      in C6 cells, mainly due to Mao but also due to Saishin at least in part, and the
      counteraction of Bushi. The former effect is mediated by formation of cAMP and
      resulting inhibition of ERK1/2-phosphorylation.

PMID- 15256756
TI  - Effect of endocrine disrupting chemicals on lipopolysaccharide-induced tumor
      necrosis factor-alpha and nitric oxide production by mouse macrophages.
AB  - Little is known about the development of infectious diseases during exposure to
      endocrine disrupting chemicals (EDCs), although several studies have reported on
      the effect of EDCs on the immune function of the human body. To assess the effect
      of EDCs on the development of infectious disease, we investigated the effect of
      eighteen possible EDCs on mouse macrophage production of tumor necrosis factor
      alpha (TNF-alpha) and nitric oxide (NO) in response to bacterial endotoxin in
      vitro and ex vivo. Of chemicals we examined, simazine, nitrofen, and benzyl butyl
      phthalate inhibited lipopolysaccharide (LPS)-induced TNF-alpha production by
      mouse macrophage cell line RAW 264 in vitro. Carbaryl, alachlor, nonylphenol,
      octylphenol, tributyltin, and triphenyltin inhibited LPS-induced NO production in
      vitro, whereas 2,4-dichlorophenoxy acetic acid and bisphenol A enhanced its
      production. Zineb and alachlor, on the other hand, enhanced LPS-induced TNF-alpha
      production by mouse peritoneal macrophages ex vivo, while alachlor inhibited
      LPS/interferon-gamma-induced NO production ex vivo. These results indicate that
      some EDCs exert modulatory activity on endotoxin-induced macrophage activation
      either positively or negatively, suggesting that these compounds may affect the
      development of infectious diseases. This is the first report that systematically
      compared the effect of EDCs on LPS action.

PMID- 15256757
TI  - Inhibitory effect of traditional Turkish folk medicines on aldose reductase (AR)
      and hematological activity, and on AR inhibitory activity of quercetin-3-O-methyl
      ether isolated from Cistus laurifolius L.
AB  - The inhibitory effects of 40 extracts prepared from 38 traditional Turkish folk
      medicines on human aldose reductase (h-AR) and hematological activity were
      investigated. Seven plants containing 5 species of Cistus genus exhibited a
      potent inhibition of h-AR. Ferulago amani (root) inhibited the platelet
      aggregation induced by sodium arachidonate, while C. laurifolius (fruit) was
      found to possess strong inhibition in the blood coagulation assay. An AcOEt
      extract derived from the leaf of C. laurifolius was purified to isolate three
      known flavonoids. The activity of one, quercetin-3-O-methyl ether, was found to
      be as potent as that of eparlestat, which is known to be a remedy for treating
      complications associated with diabetes.

PMID- 15256758
TI  - Tyrosinase-inhibitory furanocoumarin from Angelica dahurica.
AB  - An extract of the roots of Angelica dahurica BENTH. et HOOK. (Umbelliferae)
      showed potential tyrosinase inhibition against mushroom tyrosinase. Employing a
      bioassay-linked HPLC method, followed by semipreparative HPLC, the active
      principle was isolated and characterized as 9-hydroxy-4-methoxypsoralen.

PMID- 15256759
TI  - Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and
      II inhibition and cytotoxicity.
AB  - Activity-guided fractionation based on topoisomerase I inhibitory activity lead
      to the isolation of ten lignans (1-10) from the methylene chloride extract of the
      bark of Machilus thunbergii SIEB. et ZUCC. (Lauraceae). These were identified as
      machilin A (1), erythro-austrobailignan-6 (2), meso-monomethyl dihydroguaiaretic
      acid (3), meso-dihydroguaiaretic acid (4), galbacin (5), machilin F (6),
      nectandrin A (7) nectandrin B (8), (-)-acuminatin (9) and (7S,8S)-7-(4-hydroxy-3
      methoxyphenyl)-1'-formyl-3'-methoxy-8-methyldihydrobenzofuran (10) by spectral
      evidence. In DNA topoisomerase I and II assays in vitro at a concentration of 100
      microM, 4 showed the most potent inhibitory activity, 93.6 and 82.1% inhibition,
      respectively, and 8 showed 79.1 and 34.3% inhibition, respectively. All of these
      compounds exhibited weak or no cytotoxicities against either the human colon
      carcinoma cell line (HT-29) or the human breast carcinoma cell line (MCF-7).

PMID- 15256760
TI  - Effect of gamma-oryzanol on cytochrome P450 activities in human liver microsomes.
AB  - The effects of gamma-oryzanol, a drug mainly used for the treatment of
      hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human
      liver microsomes were investigated to predict drug interactions with gamma
      oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions
      were used in this study: CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation,
      CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O
      debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19
      mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated bufuralol 1'
      hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated
      testosterone 6beta-hydroxylation. gamma-Oryzanol had little inhibitory effects on
      CYP activities, indicating that this compound would not be expected to cause
      clinically significant interactions with other CYP-metabolized drugs at expected
      therapeutic concentrations.

PMID- 15256761
TI  - Tissue distribution after intravenous dosing of micafungin, an antifungal drug,
      to rats.
AB  - The tissue distribution after an intravenous dose of micafungin (1 mg/kg), a new
      echinocandin-like lipopeptide antifungal agent, to male rats was investigated.
      Micafungin in plasma disappeared biexponentially with a terminal half-life of
      5.03 h. Micafungin concentrations in liver, kidney, and lung at the first
      sampling time (5 min) after dosing were 1.15, 1.64, and 2.58-fold higher than the
      plasma concentration, and the AUC(0- infinity ) were 1.61, 3.42, and 2.89-fold
      higher than that for plasma. The terminal half-lives for these tissues were 5.14,
      4.87, and 5.31 h, respectively, which were comparable to those for plasma. These
      results suggest that micafungin distributes rapidly and moderately into tissues
      such as the liver, kidney, and lungs, and that the concentrations in tissues
      decreased in parallel with the unchanged drug in plasma.

PMID- 15256762
TI  - Molecular mechanisms of cholesteryl ester transfer protein deficiency in
      Japanese.
AB  - Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of
      cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B
      containing lipoproteins. Since CETP regulates the plasma levels of HDL
      cholesterol and the size of HDL particles, CETP is considered to be a key protein
      in reverse cholesterol transport (RCT), a protective system against
      atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was
      demonstrated by the discovery of CETP-deficient subjects with marked
      hyperalphalipoproteinemia (HALP). Genetic CETP deficiency is the most important
      and common cause of HALP in the Japanese. Ten mutations of the CETP gene have
      been demonstrated as causes of HALP, including two common mutations: an intron 14
      splicing defect (Int14 + 1 G --> A) and an exon 15 missense mutation (D442G). The
      subjects with CETP deficiency show a variety of abnormalities in the
      concentration, composition, and function of both HDL and low density lipoprotein
      (LDL). CETP deficiency is considered a physiological state of impaired RCT, which
      may possibly lead to the development of atherosclerosis despite high HDL
      cholesterol levels. However, the pathophysiological significance of CETP in terms
      of atherosclerosis has been controversial. Epidemiological studies in Japanese
      Americans living in Hawaii and Japanese in the Omagari area, where HALP subjects
      with an intron 14 splicing defect of the CETP gene are markedly frequent, have
      shown a relatively increased incidence of coronary atherosclerosis in CETP
      deficiency. On the other hand, the TaqIB polymorphism-B2 allele with low CETP
      mass and increased HDL cholesterol has been related to a decreased risk for
      coronary heart disease (CHD) in many studies, including the Framingham Offspring
      Study. The current review focused on the characterization of the Japanese
      subjects with CETP deficiency, including our recent findings.

PMID- 15256763
TI  - Role of macrophage-derived histamine in atherosclerosis-- chronic participation
      in the inflammatory response --.
AB  - The atherosclerotic intimal lesion contains endothelial cells, smooth muscle
      cells, monocytes/macrophages and T lymphocytes, which constitute a histamine
      cytokine network that participates in chronic inflammatory responses.
      Monocytes/macrophages and T lymphocytes express the histamine-producing enzyme
      histidine decarboxylase (HDC), and specific histamine receptors (HHR), which are
      switched from HH2R to HHR1 during macrophage differentiation. Endothelial and
      smooth muscle cells also express HHR in response to histamine. The effects of
      histamine on these cells include a regulation of atherosclerosis-related events
      such as cell proliferation, expression of matrix metalloproteinase, adhesion
      molecules and cytokines. Furthermore, recent studies have indicated that
      histamine and the activation of its specific receptors modulate the Th1/Th2
      balance in inflammatory lesions through the regulation of cytokine production
      from inflammatory cells. The histamine-cytokine network in the atherosclerotic
      intima could regulate inflammatory and immune responses, including Th1/Th2
      balance, and contribute to atherogenesis.

PMID- 15256765
TI  - Clinical features of familial hypercholesterolemia in Japan in a database from
      1996-1998 by the research committee of the ministry of health, labour and welfare
      of Japan.
AB  - Familial hypercholesterolemia (FH) is one of the most common primary
      hyperlipidemias, characterized by a heterozygous or homozygous phenotype for a
      severe serum low-density lipoprotein (LDL)-cholesterol level and advanced
      atherosclerosis, leading to coronary artery diseases (CAD). Various kinds of
      mutations in the LDL receptor gene responsible for the genetic disease have been
      identified since the human LDL receptor gene has been identified. In this study,
      the clinical features of FH were investigated using a database based on
      nationwide surveillance for primary hyperlipidemia and related disorders by the
      Research Committee on Primary Hyperlipidemia. The clinical features and the
      frequencies of accompanying vascular diseases in 660 cases of FH homozygotes and
      heterozygotes showed that the incidence of CAD was negatively associated with
      plasma HDL-cholesterol levels, but not with plasma LDL-cholesterol levels, in 641
      FH heterozygotes. Risk factor analyses revealed that hypertension, male, smoking,
      low HDL-cholesterol levels, age > 50 y, diabetes mellitus, and
      hypertriglyceridemia were positive risk factors for CAD. The summarized gene
      analysis in FH heterozygotes showed at least 4 mutations in the LDL receptor gene
      as common mutations in Japan. The average serum lipids and frequency of CAD based
      on each common mutation suggested that their clinical features are in part
      determined by responsive mutations in the LDL receptor gene.

PMID- 15256764
TI  - Mutations in Japanese subjects with primary hyperlipidemia--results from the
      Research Committee of the Ministry of Health and Welfare of Japan since 1996--.
AB  - Primary hyperlipidemia is caused by various molecular defects in lipid
      metabolism. The Research Committee on Primary Hyperlipidemia organized by the
      Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour
      and Welfare) has investigated reported mutations in Japanese patients with
      primary hyperlipidemia and related disorders (including hypolipidemia), and has
      created a database based on the questionnaire sent to the members of council
      board of the Japan Atherosclerosis Society. Mutations in the following genes were
      investigated: low density lipoprotein receptor, lecithin: cholesteryl
      acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A
      II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and
      cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary
      hyperlipidemia and related disorders has been registered with the Research
      Committee, and 190 mutations in 15 genes had been reported, showing a marked
      variation in Japanese patients with primary hyperlipidemia and related disorders.
      So-called "common mutations" have been described in Japanese patients with
      familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic
      defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL
      is speculated to be the most prevalent genetic hyperlipidemia, and further
      investigations should be performed to elucidate the molecular mechanisms of FCHL

PMID- 15256767
TI  - Tropoelastin inhibits vascular calcification via 67-kDa elastin binding protein
      in cultured bovine aortic smooth muscle cells.
AB  - In cases of vascular calcification, the expression of tropoelastin is down
      regulated, which most likely decreases elastic fiber formation. However, the
      function of tropoelastin in vascular calcification remains unknown. We
      investigated whether tropoelastin affects the induction of vascular
      calcification. Calcification was induced using inorganic phosphate in cultured
      bovine aortic smooth muscle cells. The increase in tropoelastin due to the
      addition of recombinant bovine tropoelastin (ReBTE; 1 or 10 microg/ml) or beta
      aminopropionitrile (25 microg/ml) significantly inhibited calcification at day 6,
      as assessed by the o-cresolphthalein complexone method. The addition of an
      elastin-derived peptide, VGVAPG peptide (0.1-1,000 nM), inhibited calcification
      at day 6 in a dose-dependent manner. In addition, these responses of beta
      aminopropionitrile, ReBTE, and VGVAPG peptide were confirmed using von Kossa
      staining. To examine whether ReBTE inhibited calcium deposition via the elastin
      binding protein, lactose and elastin-specific antibody were used. The combination
      of lactose (20 mM) or this antibody (50 microg/ml) with ReBTE (10 microg/ml)
      attenuated the inhibition of calcification. These results suggest that increased
      tropoelastin inhibits vascular calcification in this model via the interaction
      between tropoelastin and elastin binding protein.

PMID- 15256766
TI  - Clinical efficacy and safety of rosuvastatin in Japanese patients with
      heterozygous familial hypercholesterolemia.
AB  - Rosuvastatin is a new statin that has been shown to produce substantial dose
      dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western
      and Japanese hypercholesterolemic patients. Rosuvastatin efficacy and safety were
      assessed in an open-label, dose-titration trial of 37 Japanese patients with
      heterozygous familial hypercholesterolemia. After an 8-week dietary lead-in
      period, patients received rosuvastatin on the following schedule: 10 mg/day
      during weeks 0-6; 20 mg/day during weeks 6-12, and 40 mg/day for weeks 12-18.
      Mean percentage reductions from baseline in LDL-C (49.2-56.7%), total cholesterol
      (39.4-45.4%), and non-high-density lipoprotein cholesterol (non-HDL-C) (46.7
      54.3%) were highly significant at each dose (p < 0.0001). Similar significant
      reductions in triglycerides (18.2-25.0%; p < 0.006) and increases in HDL-C (9.6
      13.6%; p < 0.005) were observed. Rosuvastatin was well tolerated. Two patients
      withdrew from the study because of adverse events unrelated to the study
      treatment. No patients had clinically significant elevations in liver
      transaminases. Two patients exhibited a single increase in creatine kinase (one
      unrelated to study treatment, the other possibly related) with no muscle
      symptoms. Rosuvastatin produced significant beneficial changes in all lipid
      parameters in Japanese patients with heterozygous familial hypercholesterolemia
      and was well tolerated.

PMID- 15256768
TI  - Enhanced susceptibility of LDL to oxidative modification in a CTX patient:- role
      of chenodeoxycholic acid in xanthoma formation.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease,
      causing multiple xanthomas in tendons and the brain. The underlying biochemical
      defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved
      in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of
      chenodeoxycholic acid (CDCA). It has been reported that administration of CDCA to
      CTX patients improves neurological disorders and xanthomas of the Achilles
      tendon. The present study investigated the effect of CDCA on the mechanism of
      cholesterol accumulation in macrophages, the major cells in xanthoma. The LDL
      from the patients in this study was significantly more susceptible to oxidative
      modification than normal LDL, and supplement therapy with CDCA resulted in an
      improvement in the susceptibility to oxidative modification. In the incubation of
      CDCA with plasma, 13% of the CDCA added to serum was recovered in the LDL
      fraction. In addition, supplementation with CDCA enhanced cholesteryl ester
      transfer protein (CETP) activity and reduced high-density-lipoprotein cholesterol
      levels in the plasma. This evidence suggests that the multiple xanthomas observed
      in CTX may be induced by increased oxidized LDL and the low activity of CETP,
      both of which are caused by a lack of CDCA.

PMID- 15256769
TI  - The relationship of abdominal fat mass assessed by helical or conventional
      computed tomography to serum leptin concentration.
AB  - In the present study, we focused on the relationship of intra-abdominal visceral
      fat (VF) or subcutaneous fat (SF) mass to serum leptin levels, and also on the
      relationship of leptin to serum lipid and lipoprotein concentration. Subjects
      with obesity (26 men, 26 women) were recruited for this study. We obtained
      helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch
      (table speed in relation to slice thickness), starting at the upper edge of the
      liver and continuing to the pelvis. The intra-abdominal visceral fat (VF) volume
      was measured by drawing a line within the muscle wall surrounding the abdominal
      cavity. The abdominal SF volume was calculated by subtracting the VF volume from
      the total abdominal fat volume. By comparison, the abdominal VF and SF areas were
      determined at the umbilical level by the established slice-by-slice CT scanning
      technique. We found: 1) abdominal SF mass, either as volume or area, was a more
      important determinant of serum leptin than was VF mass; 2) among TC, TG, HDL-C
      and LDL-C, only TG had a positive correlation to serum leptin levels in men,
      whereas in women no lipid parameters had any relationship with leptin; and 3) VF
      mass had a positive correlation to serum TC and TG in men, whereas SF did not.
      The present study provides considerable evidence on the relationship between
      abdominal fat mass and serum leptin, and shows that the relationships between
      serum leptin and serum lipids and lipoproteins are not straightforward. We also
      suggest that fat area measured by conventional CT is a better indicator than its
      corresponding volume assessed by helical CT, based on the present results showing
      its closer association to serum lipids.

PMID- 15256770
TI  - Neurogenin 3 is a key transcription factor for differentiation of the endocrine
      pancreas.

PMID- 15256771
TI  - Mitochondrial DNA and human thyroid diseases.
AB  - Cells of the thyroid tissue, either diseased or normal, can accumulate altered
      mitochondrial genomes in primary lesions and in surrounding parenchyma. Depending
      on the experimental approaches and the extent of the mutational process, it has
      been possible to demonstrate the occurrence of homoplasmic or heteroplasmic point
      mutations, presence of a common deletion and random large-scale mtDNA aberrations
      in various pathological states. Point somatic mutations documented in 5-60% of
      thyroid tumors do not concentrate in obvious hotspots but tend to cluster in
      certain regions of the mitochondrial genome and their distribution may differ
      between carcinomas and controls. Large-scale deletions in mtDNA are quite
      prevalent in healthy and diseased thyroid; however, the proportion of aberrant
      mtDNA molecules accounts for a very small part of total mtDNA and does not seem
      to correlate with pathological characteristics of thyroid tumors. Common deletion
      is most abundant in Hurthle cell tumors, yet it also occurs in other thyroid
      diseases as well as in normal tissue. The principal difference between the common
      deletion and other deletion-type mtDNA molecules is that the former does not
      depend on the relative mtDNA content in the tissue whereas in a subset of thyroid
      tumors, such as radiation-associated papillary carcinomas and follicular
      adenomas, there is a strong correlation between mtDNA levels and prevalence of
      large-scale deletions. Relative mtDNA levels by themselves are elevated in most
      thyroid tumors compared to normal tissue. Distinct differential distribution and
      prevalence of mutational mtDNA burden in normal tissue and thyroid lesions are
      suggestive of the implication of altered mtDNA in thyroid diseases, especially in
      cancer.

PMID- 15256772
TI  - Lipoatrophic diabetes in an elderly woman: clinical course and serum
      adipocytokine concentrations.
AB  - Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology
      remains unknown. Pathophysiology of this disorder is characterized by generalized
      loss of body fat associated with an infrequent form of diabetes mellitus
      (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the
      severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be
      congenital or acquired. In the acquired form, metabolic disturbances usually
      begin in the first years of life and the response to conventional treatment is
      very poor. Some alterations in serum adipocytokines have been described in this
      disease. We report the case of a 74-year-old woman with acquired generalized
      lipodystrophy who presented with low-normal serum concentrations of leptin, low
      adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was
      initially treated with fenofibrate, metformin and high doses of subcutaneous
      insulin achieving an adequate metabolic control. During this period, serum
      adipocytokines were periodically measured. We comment on the different
      etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

PMID- 15256773
TI  - A case of acquired deficiency of pituitary GH, PRL and TSH, associated with type
      1 diabetes mellitus.
AB  - A 75-year-old male showed combined anterior pituitary hormone deficiency (CPHD).
      Basal and TRH-stimulated PRL levels were undetectable. Basal and GRH-stimulated
      GH levels were very low, and could barely be measured by means of an
      ultrasensitive enzyme immunoassay. In addition, basal TSH levels were under the
      normal limit, and TRH-stimulated TSH secretions were impaired. On the other hand,
      the secretions of ACTH, LH and FSH remained intact. There was no mutation of Pit
      1 gene in this patient, and immunohistochemical studies using human pituitary and
      the patient's serum showed no positive staining. The HLA types frequently
      detected in lymphocytic hypophysitis were recognized, supporting the view that
      the CPHD in this case may be caused by lymphocytic hypophysitis, although
      magnetic resonance imaging of the pituitary gland showed no specific findings.
      Interestingly, a high titer of anti-glutamic acid decarboxylase antibody,
      suggested that the patient suffered from type 1 diabetes mellitus (DM). Five
      years ago, his thyroid function was normal and the treatment of DM with oral
      hypoglycemic agent was effective, indicating that the onset of both diseases at
      least occurred within the last half decade. We report here a rare case of SPIDDM
      with CPHD which might be caused by lymphocytic hypophysitis.

PMID- 15256774
TI  - The diagnostic standard of preclinical Cushing's syndrome: evaluation of the
      dexamethasone suppression test using various cortisol kits.
AB  - Incidental discovery of an adrenal mass, the so-called adrenal incidentaloma, has
      been increasing due to the advances in non-invasive diagnostic imaging tools. The
      criteria of diagnosis for preclinical Cushing's syndrome (preCS) in Japan were
      made by Nawata et al. supported by the Ministry of Health and Welfare in 1995.
      The results of suppression of cortisol by dexamethasone (DEX) (plasma cortisol
      above 3 microg/dl after 1 mg of DEX and above 1 microg/dl after 8 mg of DEX) are
      essential for the diagnosis of preCS due to an adrenal adenoma. However, plasma
      cortisol levels after the two doses of DEX suppression tests were found to be
      discrepant and repeated DEX suppression tests sometimes yielded different
      results. Therefore, we examined the cortisol values of DEX suppression tests in
      patients with preCS using four different cortisol assay kits: Amerlex cortisol
      kit (AMA), SPAC-S cortisol kit (SPA), ADVIA-Centaur cortisol assay (ADV) and
      ECLusys 2010 cortisol assay (ECL). The diagnosis for preCS was done using the AMA
      kit. Correlation between the kits was good. However, cortisol levels measured by
      SPA, ADV and ECL were lower than those measured by AMA. In the 1 mg DEX test, the
      cortisol levels measured with the SPA, ADV and ECL kits were suppressed in 2
      patients with preCS. With 8 mg of DEX, cortisol levels measured with the SPA and
      ADV kits were suppressed in 2 patients with preCS. The diagnosis of preCS is
      decided by the cortisol kit used, but the cortisol levels differ among the kits.
      It is suggested that the lack of the standardization of cortisol measurement is
      one of the causes of confusion in the diagnosis of preCS.

PMID- 15256775
TI  - Anaplastic thyroid carcinoma with humoral hypercalcemia of malignancy (HHM): an
      autopsy case report.
AB  - An 84-year-old woman was admitted to our hospital for the examination and
      treatment of painful right thyroid swelling on August 2, 2002. Thyroid
      ultrasonography showed a mass of about 6 cm in diameter at the right thyroid
      lobe. Aspiration biopsy cytology (ABC) of her mass showed a thyroid carcinoma.
      Her neck mass was cold on (123)I scintigraphy and hot on both early- and delayed-
      phase (201)Tl scintigraphy. Whole body (67)Ga scintigraphy scan showed a strong
      hot accumulation in the area from the right thyroid lobe to the right lateral
      lobe. Multiple lung tumors were observed from chest computed tomography (CT)
      scans. She was diagnosed as having an anaplastic thyroid carcinoma with
      metastatic lung tumors. As her thyroid carcinoma was inoperable, percutaneous
      injection therapy of lipiodol and ethanol (lip-PEIT) against the primary thyroid
      carcinoma was performed twice a week. However, the thyroid carcinoma gradually
      enlarged and oppressed her trachea. Two months after the initiation of lip-PEIT,
      parathyroid hormone-related protein (PTHrP)-dependent hypercalcemia was diagnosed
      because serum levels of calcium, phosphate and intact-PTHrP were 2.72 mmol/l
      (10.9 mg/dl), 0.71 mmol/l (2.2 mg/dl), 3.2 pmol/l, respectively. The
      hypercalcemia was reduced by the use of pamidronate. After one week she died of
      an airway obstruction caused by the developing thyroid carcinoma. Carcinoma cells
      with a mixed papillary and squamoid pattern were positively stained
      immunohistochemically by anti-PTHrP(1-34) antisera. Herein, we report a rare
      autopsy case of a PTHrP-producing thyroid carcinoma.

PMID- 15256776
TI  - Assessment of anxiety in subclinical thyroid disorders.
AB  - It is well known that manifest thyroid dysfunction causes mood disorders. In the
      literature there are few studies related with subclinical thyroid dysfunction and
      anxiety. We aimed to determine if there exists a relation between the anxiety and
      subclinical thyroid dysfunction. This study was carried out in the Meram Medical
      Faculty of Selcuk University, Department of Endocrinology and Metabolism. Eighty
      five outpatients were enrolled into the study. In the presence of normal fT(3)
      and fT(4), patients were grouped as subclinical hyperthyroid with TSH lower than
      0.1 mU/L (n = 24), subclinical hypothyroid with TSH higher than 4.5 mU/L (n = 32)
      and euthyroid subjects (n = 29). Beck's Anxiety Inventory (BAI) was administered
      to all patients. There was no any statistically significant difference between
      euthyroid and study groups in terms of age, gender, weight and height (p<0.05).
      One-way ANOVA showed that both of the subclinical hypothyroid and subclinical
      hyperthyroid groups had significantly higher anxiety scores than euthyroid group
      (F: 11.4, p<0.001). Manifest hypothyroidism and hyperthyroidism, as causes of
      mental and neurological dysfunction have been known for a long time, but the
      relation between subclinical thyroid dysfunction and anxiety is less well
      studied. We have found that subclinical thyroid dysfunction increases the anxiety
      of patients whether hyperthyroid or hypothyroid. Overlap of symptoms common to
      both thyroid dysfunction and anxiety is an important limitation in this study.
      Mood changes especially anxiety due to subclinical thyroid dysfunction may have
      an important impact on the patient's quality of life. Negative effect on quality
      of life may be an indication of treatment in these patients. It is the first
      study evaluating anxiety in subclinical hypothyroidism in the literature.

PMID- 15256777
TI  - Papillary thyroid carcinoma associated with familial adenomatous polyposis:
      molecular analysis of pathogenesis in a family and review of the literature.
AB  - We found a case of a papillary thyroid carcinoma that was accompanied by a
      familial adenomatous polyposis (FAP) in a 29-year-old female. She had hundreds of
      adenomas inside the entire colon and a congenital hypertrophy of the retinal
      pigmented epithelium (CHRPE). The patient underwent a total thyroidectomy and a
      central compartment neck node dissection. Gross examination of the thyroid
      identified two solid and cystic lesions. The pathological finding of thyroid
      cancer revealed a mixture of a peculiar nuclear clearing, cribriform, morula
      formation, trabecular and papillary pattern. The patient's brother had undergone
      a total colectomy due to FAP at the age of 25. Genetic analyses of the patient's
      family members revealed that she and her brother had the same germline mutation,
      in which five nucleotides (AAAGA) were deleted from codon 1309 of the adenomatous
      polyposis coli (APC) gene exon 15. Strong and frequent immunoreactivities of beta
      catenin and p53 were evident in the tumor tissue. At the time of writing, a
      preventive colectomy was still under consideration for the patient. Genetic
      counseling was given to the other family members, who were not attacked by this
      disease, in order to allay their fears of cancer.

PMID- 15256778
TI  - The role of corticosterone in the metabolic recovery after intrasplenic adrenal
      autotransplantation in rats.
AB  - Transplantation of adrenal cortical tissue may represent an alternative treatment
      to reestablish glucocorticoid secretion in adrenal insufficiency. In the present
      work, performed in adrenalectomized rats and adrenalectomized rats with a
      complete autotransplanted adrenal into the spleen, several hormones and
      biochemical parameters were measured and compared to control animals, in order to
      examine hormone interactions. Rats were sacrificed three weeks after surgery, and
      plasma and tissue samples were obtained for hormone and biochemical measurements.
      In adrenalectomized animals, plasma corticosterone, aldosterone and insulin
      levels were profoundly decreased, whereas in autotransplanted rats plasma
      corticosterone levels showed a partial recovery, aldosterone plasma
      concentrations remained low, and plasma insulin levels increased to values close
      to those of the controls. Both groups showed a marked elevation of plasma ACTH
      levels, as well as significantly increased plasma glucagon concentrations. In
      autotransplanted animals, most of the biochemical parameters, which were altered
      in adrenalectomized rats, returned to normal levels. These results suggest that
      increased glucagon levels in adrenalectomized and autotransplanted animals, may
      contribute to the marked increase of plasma ACTH, and could also be important in
      the recovery of plasma glucose and hepatic glycogen observed in autografted rats.
      Since high glucagon concentrations alone were unable to normalize carbohydrate
      levels in adrenalectomized animals, it appears that glucagon can act only in the
      presence of corticosterone.

PMID- 15256779
TI  - JunD-menin interaction regulates c-Jun-mediated AP-1 transactivation.
AB  - The gene responsible for multiple endocrine neoplasia type 1, MEN1, encodes the
      610-amino acid-protein, menin. Although menin has been reported to bind AP-1
      transcription factor JunD and suppress its transcriptional activity, little is
      known about its molecular mechanisms and physiological role. To better understand
      the function of menin and its significance in tumorigenesis, we investigated the
      effect of wild-type and mutant menin proteins on AP-1 transactivation. In COS
      cells, wild-type menin suppressed JunD-mediated transactivation in a dose
      dependent manner, while it augmented c-Jun-mediated transactivation also in a
      dose-dependent manner. These effects were lost or reduced in all menin mutants
      examined. Electrophoretic mobility shift assay using AP-1 binding elements as a
      probe revealed that menin does not affect binding of c-Jun to DNA. Coexpression
      of menin mutants did not affect the function of wild-type menin. Coexpression of
      JunD amino-terminal fragment abolished menin-mediated enhancement of c-Jun
      transactivation, suggesting that Menin-JunD interaction may negatively regulate
      the enhancing effect of menin on c-Jun-mediated transactivation in COS cells.

PMID- 15256780
TI  - Serum levels of 20 kilodalton human growth hormone (20K-hGH) in patients with
      acromegaly before and after treatment with octreotide and transsphenoidal
      surgery.
AB  - Circulating human GH (hGH) consists of several molecular isoforms. It was
      previously reported that the proportion of 20 kilodalton hGH (20K-hGH) was
      elevated in the serum of patients with active acromegaly. In this study, we
      investigated the effects of octreotide and transsphenoidal adenomectomy on the
      proportion of 20K-hGH in the serum of 7 acromegalic patients. To achieve an acute
      effect, octreotide (100 microg) was subcutaneously injected as a bolus. To
      observe the chronic effects of octreotide therapy and surgery, serum samples were
      obtained by repetitive blood sampling before and 3 to 8 weeks after treatment.
      Serum levels of 20K-hGH and 22 kilodalton hGH (22K-hGH) were determined by
      specific enzyme-linked immunosorbent assay. A bolus injection of octreotide
      elicited a parallel decrease in serum 22K-hGH and 20K-hGH, resulting in an
      unchanged proportion of 20K-hGH to total circulating hGH. The proportion of 20K
      hGH was decreased in 4 of 4 patients 4 to 7 weeks after surgery and in 2 of 4
      patients after chronic treatment with octreotide for 3 to 8 weeks. The proportion
      of serum 20K-hGH was positively related to mean serum 20K-hGH as well as serum
      total hGH levels, but not with serum IGF-I levels. These findings suggest that
      high serum levels of 20K-hGH or total hGH per se might elicit a chronic change in
      the clearance kinetics of 20K-hGH and increase the proportion of 20K-hGH in
      acromegalic patients.

PMID- 15256781
TI  - Annexin 5 inhibits thyrotropin releasing hormone (TRH) stimulated prolactin
      release in the primary culture of rat anterior pituitary cells.
AB  - Annexin 5, a novel calcium-phospholipid binding protein, is thought to be
      involved in hormone secretion by the anterior pituitary gland. Gonadotropin
      releasing hormone stimulates annexin 5 synthesis, which, in turn, enhances
      gonadotoropin secretion. On the other hand, annexin 5 was shown to inhibit
      prolactin release in vitro. To understand the nature of the opposing effects of
      annexin 5 on these two major pituitary hormones, the present study examines the
      inhibitory effect of annexin 5 on prolactin release in relation to thyrotropin
      stimulating hormone (TRH) using primary cultures of anterior pituitary cells of
      adult female rats. While recombinant rat annexin 5 was found to have little
      effect on basal prolactin release, it significantly inhibited TRH-stimulated
      prolactin release. Addition of specific anti-annexin 5 serum to the culture
      increased basal prolactin release in a concentration dependent manner, and no
      further increase in prolactin release was observed following application of TRH
      in the presence of anti-annexin 5. The enhanced basal prolactin release induced
      by anti-annexin 5 was reversed by the simultaneous administration of
      indomethacin, an inhibitor of cyclooxygenase. These results demonstrate that
      endogenous pituitary annexin 5 exerts an inhibitory effect on prolactin release
      and suggest that this is attained by suppression of eicosanoid synthesis in
      vitro.

PMID- 15256782
TI  - An assessment of bone mineral density in patients with Addison's disease and
      isolated ACTH deficiency treated with glucocorticoid.
AB  - Glucocorticoid replacement therapy needs to be tailored to individual patient's
      requirements in order to avoid risk of over or under medication. We measured bone
      mineral density (BMD) of lumbar spine using dual X-ray absorptiometory in 10
      patients with Addison's disease and 5 patients with isolated ACTH deficiency
      receiving glucocorticoid replacement therapy. We also examined the effect of
      glucocorticoid replacement on BMD. Decreased %BMD (less than 80% of age-matched
      controls) was found in 2 female patients who had received hydrocortisone at a
      dose of 14.8 and 15.4 mg/m(2)/day. In contrast, no patient receiving a
      hydrocortisone dose of less than 12.4 mg/m (2)/day had decreased %BMD. There was
      no correlation between %BMD and hydrocortisone dose (mg/m(2)), duration of
      therapy, or cumulative hydrocortisone dose when treated with appropriate dose of
      hydrocortisone (<13.6 mg/m(2)). There was also no statistically significant
      difference in %BMD with age. We concluded that long-term glucocorticoid
      replacement therapy does not induce bone loss in patients with glucocorticoid
      deficiency unless an excessive dose of hydrocortisone is given.

PMID- 15256783
TI  - Is thyroid follicular cancer in Japanese caused by a specific t(2; 3)(q13; p25)
      translocation generating Pax8-PPAR gamma fusion mRNA?
AB  - A recent western study reports that t(2; 3)(q13; p25) translocation resulting in
      the expression of the Pax8-PPAR gamma fusion gene in patients with thyroid
      follicular carcinoma (FTC) occurs with high incidence (63%). Furthermore, the
      products of the fusion gene were shown to suppress the function of PPAR gamma in
      a predominantly negative manner, conferring them with an oncogenic potential. We
      examined the expression of this fusion gene in FTC in Japanese patients. From
      1989 to 2000, six cases with FTC were surgically treated at our institute. In
      these carcinoma samples, the expression of mRNAs for the Pax8-PPAR gamma fusion
      product was analyzed by nested RT-PCR. Their expression was also studied in other
      thyroid nodules (12 adenomatous goiters, 12 follicular adenomas, 12 papillary
      carcinomas and 12 normal thyroid tissues) obtained at surgery during the same
      period. Pax8-PPAR gamma fusion mRNA was not detected in any FTC samples nor in
      the other samples. Furthermore, none of the 6 FTCs, one follicular adenoma or one
      normal thyroid analyzed by fluorescence in situ hybridization (FISH) exhibited
      Pax8-PPAR gamma gene fusion. These findings are in contrast to previous reports
      and indicate that ethnic background may affect the translocation.

PMID- 15256784
TI  - Adrenocorticotropic hormone and 17-hydroxyprogesterone levels during high-dose
      glucocorticoid supplement for the management of clitoroplasty of CYP21A2
      deficiency.
AB  - ACTH and 17-hydroxyprogesterone (17OHP) levels during clitoro- and labinoplasty
      for CYP21A2 deficiency have not been reported. In this study, we measured these
      levels during surgery. Intensive glucocorticoid supplement (IGS Tx; intravenous
      bolus injection of daily dose (14.6 to 22.2 mg/m(2)) of hydrocortisone followed
      by continuous infusion of three times the daily dose for 24 hours) was done to
      eight patients for surgery. ACTH and 17OHP levels were generally suppressed
      during operation by this protocol, but mid-surgical elevations of ACTH and 17OHP
      levels were observed in four out of the eight. In another three patients than the
      eight as described, oral dexamethasone pretreatment (1 mg/m(2)) was administered
      for two days before surgery in addition to IGS Tx. ACTH and 17OHP levels were
      completely suppressed throughout operation, indicating that this kind of
      additional pretreatment is more effective approach.

PMID- 15256785
TI  - A case of cystic lymphocytic hypophysitis with cacosmia and hypopituitarism.
AB  - Lymphocytic hypophysitis is a rare inflammatory disease of the pituitary gland
      that is being increasingly recognized as a cause of hypopituitarism. This
      condition may be due to an autoimmune pituitary destruction which usually occurs
      in young women during pregnancy or in the immediate postpartum period. We
      describe a case of cystic pituitary mass in a thirty-eight year-old woman
      presenting with nausea, vomiting, cold intolerance, blurring of vision and the
      presence of disagreeable odors for a one-month period. She had secondary
      amenorrhea and galactorrhea for three months. Combined anterior pituitary
      stimulation test confirmed the diagnosis of hypopituitarism. Magnetic resonance
      imaging scan with enhancement showed a huge cystic sellar mass with suprasellar
      extension and thickening of the pituitary stalk. Transsphenoidal exploration was
      performed with preoperative diagnosis of pituitary macroadenoma with cystic
      necrosis. Histological examination revealed lymphocytic hypophysitis
      characteristic of diffuse, dense lymphocytes and plasma cells infiltration with
      surrounding interstitial reactive fibrosis. Postoperatively, the patient's
      olfactory function returned to normal but combined anterior pituitary stimulation
      test showed persistence of hypopituitarism with mild hyperprolactinemia.
      Prednisolone, thyroxine and estrogen replacements were started and clinical
      symptoms were much improved. In summary, we report an extremely rare case of a
      woman with cystic lymphocytic hypophysitis with cacosmia and hypopituitarism,
      confirmed by histological examination.

PMID- 15256786
TI  - Reversal of streptozotocin-induced hyperglycemia by transplantation of
      pseudoislets consisting of beta cells derived from ductal cells.
AB  - The present study was conducted in an attempt to treat streptozotocin (STZ)
      induced hyperglycemia by transplanting beta cells derived from pancreatic ductal
      cells. Ductal cells obtained from neonatal rats were cultured in vitro.
      Approximately 70% of the cells were converted to insulin-secreting cells by
      incubating with betacellulin and activin A. Differentiated cells responded to a
      depolarizing concentration of potassium, tolbutamide and a high concentration of
      glucose, and insulin secretion increased by 2.5-, 2.3- and 1.6-fold,
      respectively. We then prepared pseudoislets using the differentiated cells, which
      exhibited greatly improved glucose-responsiveness, with a high concentration of
      glucose inducing a 3-fold increase in insulin secretion. We transplanted these
      pseudoislets into the portal vein of STZ-treated nude mice. Before
      transplantation, the plasma glucose concentration was above 400 mg/dl, and after
      transplantation it was markedly reduced, the effect of which persisted for two
      weeks. These results indicate that STZ-induced hyperglycemia can be treated by
      transplanting pseudoislets consisting of beta cells derived from ductal cells.

PMID- 15256787
TI  - Peripheral pulmonary embolism related to a thrombus of the inferior vena cava
      triggering fatal adrenal crisis in Sheehan's syndrome.

PMID- 15256788
TI  - Effect of etidronate on intraosseous meningioma.

PMID- 15256789
TI  - Skull Paget's disease developing into Chiari malformation.

PMID- 15256790
TI  - Stroke in young patients: etiopathogenesis and risk factors in different age
      classes.
AB  - The aim of our study was to evaluate the etiopathogenesis and the vascular risk
      factors in a consecutive series of patients with juvenile ischemic stroke. We
      enrolled 273 patients (158 males and 115 females), aged between 16 and 49 years,
      with ischemic cerebrovascular events (ICVE), including transient ischemic attack
      (TIA) or stroke, referred to our neurology ward between January 1994 and December
      2001. Our protocol included medical history, cardiac and neurological
      examinations, assessment of risk factors and laboratory tests. The instrumental
      assessment included transthoracic echocardiography (70%), transesophageal
      echocardiography (60%), conventional angiography (30%), MR angiography (30%),
      cranial computed tomography (100%) and brain MRI (48%). The ICVE was a stroke in
      60% of the cases, a reversible ischemic neurologic deficit in 14% and a TIA in
      26%. Thirty-three patients were aged less than 29, 59 were aged between 30 and 39
      and 181 between 40 and 49. The percentage of females was higher in patients aged
      less than 29 while males were prevalent in the 4th and 5th decade. The patients
      were subtyped according to etiopathogenesis. A large-vessel disease (LVD) was
      diagnosed in 43 patients (16% of the cases), mostly in patients aged more than 40
      years (36 cases). A small-vessel disease (SVD) was found in 48 patients (17% of
      cases), mostly in patients aged more than 40 years (41 cases). A cardioembolic
      stroke (CE) was diagnosed in 66 patients (24% of the cases). In the majority of
      the cases, the cardiopathies were at low-uncertain embolic risk: patent foramen
      ovale (PFO, 39 cases, in 8 patients associated with an atrial septal aneurism),
      atrial septal aneurism (12 cases) and myxomatous mitral valve prolapse (3 cases).
      Stroke due to other causes was found in 51 patients (19% of the cases). Arterial
      dissection, more frequently involving the carotid region, was diagnosed in 35
      patients. Coagulopathies and vasculitis were found in 5 and 6 patients,
      respectively. Stroke of unknown etiology was found in 65 patients (24% of the
      cases) with a homogeneous distribution among decades. Our study highlights the
      role of minor cardiac sources of embolism and arterial dissection in the etiology
      of juvenile ischemic stroke, whereas coagulopathies and vasculitis are less
      relevant. LVD and SVD were relevant only in the 5th decade.

PMID- 15256791
TI  - Vascular endothelial growth factor and matrix metalloproteinase 9 expression in
      human carotid atherosclerotic plaques: relationship with plaque destabilization
      via neovascularization.
AB  - BACKGROUND: The aim of this study was to evaluate the potential impact of
      vascular endothelial growth factor (VEGF) on carotid plaque destabilization in
      association with matrix metalloproteinase 9 (MMP-9) production. METHODS:
      Expression of VEGF and MMP-9 were determined immunohistochemically in 53 human
      endarterectomized atherosclerotic carotid plaques. The relationship to carotid
      plaque characteristics, clinical data and histological morphology was
      investigated. RESULTS: VEGF and MMP-9 had parallel overexpression in the
      inflammatory cells, especially in the neovascularized plaque lesions and around
      the cholesterol crystals. Strong expression of VEGF was evident in symptomatic
      patients (p < 0.057), in high-degree stenosis (p = 0.005), and in patients with
      ischemic infarct in brain scan (p = 0.021). No relation was proved between
      molecule expression and plaque ultrasonic characteristics. CONCLUSIONS: An
      intense expression of VEGF and MMP-9 in carotid plaques is related to plaque
      instability, high degree of stenosis and presence of symptomatic carotid
      occlusive disease.

PMID- 15256792
TI  - Link between linear hyperintensity objects in cerebral white matter and
      hypertensive intracerebral hemorrhage.
AB  - BACKGROUND: We retrospectively studied the relationship between linear
      hyperintensity objects (LHOs) on T(2)-weighted magnetic resonance images (MRI) in
      the cerebral white matter and the occurrence of hypertensive intracerebral
      hemorrhage (HIH). METHODS: Forty-nine hypertensive patients with a fixed imaging
      condition MRI were classified into three groups: HIH (n = 17), ischemic stroke
      due to hypertensive vasculopathy (n = 19), and hypertension only (n = 13). After
      assessing clinical and radiological background information among these groups and
      the reliability of LHO measurements, polynomial logistic regression analysis was
      used to identify the factors relating to HIH. RESULTS: HIH had a significantly
      higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number
      showed an excellent interrater (kappa = 0.91, 95% CI = 0.87-0.94, SEM = 6.2%) and
      intrarater reliability (kappa = 0.95, 95% CI= 0.92-0.97, SEM = 4.8%), and was the
      most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05-1.60, p =
      0.017). The number of microbleeds was an additional indicator (OR = 3.73, 95% CI
      = 1.10-12.65, p = 0.034). CONCLUSIONS: LHOs are closely linked to HIH. A
      prospective, longitudinal study is needed to clarify whether LHOs can predict
      HIH.

PMID- 15256793
TI  - Quality of life after aneurysmal subarachnoid hemorrhage in the elderly.

PMID- 15256795
TI  - Lipomatous hypertrophy of the inter-atrial septum and stroke.

PMID- 15256794
TI  - Venous sinus thrombosis in a patient taking thalidomide.

PMID- 15256796
TI  - Reference values for multifrequency bioimpedance analysis in dialysis patients.
AB  - BACKGROUND: The role of multifrequency bioimpedance(MF-BIA) in the assessment of
      fluid status in dialysis patients is still not fully elucidated. Especially, the
      predictive value of reference values for extracellular water (ECW) has not yet
      been addressed. Aim of the present study was to validate cut-off values for MF
      BIA in the diagnosis of hypervolemia in dialysis patients, using strict clinical
      criteria and echocardiography as reference techniques. METHODS: 90 patients [42
      on hemodialysis; 48 on peritoneal dialysis] were divided into the following
      groups: clinically normovolemic (mean 24- or 48-hour systolic blood pressure
      below 133 mm Hg without use of antihypertensive agents; n = 12), 'hypervolemic'
      (mean systolic blood pressure above 133 mm Hg with 2 or more antihypertensive
      agents; n = 34) or undetermined (n = 44). The 80th percentile for normalized ECW
      in the clinically normovolemic patients was used as reference value. 20 healthy
      age-matched controls were included for comparison. RESULTS: The 80th percentiles
      for ECW:body weight (BW) and ECW:height in 'normovolemic' subjects were,
      respectively, 0.245 liters/kg and 10.96 liters/m in males, and 0.232 liters/kg
      and 9.13 liters/m in females. ECW:BW and ECW:height were above these values in,
      respectively, 26 (sensitivity 76%) and 29 (sensitivity 86%) of the 34
      'hypervolemic' patients. In the undetermined group, left ventricular end
      diastolic diameter was significantly different between patients with normalized
      ECW below and above these cut-off values (49.0 +/- 5.1 vs. 52.4 +/- 5.7 mm; p <
      0.05). Use of the ECW:TBW ratio resulted yielded low sensitivity (45%).
      ECW:height was lower in the 'normovolemic' dialysis patients compared to healthy
      controls (9.7 +/- 1.3 l/m versus 12.2 +/- 1.9 l/m). CONCLUSION: In our study
      population, ECW by MF-BIA, normalized for height was able to predict
      hypervolemia, based on strict clinical criteria, with a sensitivity of 86% and a
      specificity of 80%. The normalization procedure for ECW may influence the
      classification of hydration status. Strictly normotensive dialysis patients had
      lower normalized ECW than healthy control subjects.

PMID- 15256798
TI  - Regional citrate anticoagulation in critically ill patients treated with plasma
      filtration and adsorption.
AB  - BACKGROUND: In high-risk bleeding conditions conventional systemic
      anticoagulation with heparin is a contraindication to renal replacement therapy.
      We evaluate the feasibility and safety of regional citrate anticoagulation in
      high-risk bleeding conditions during coupled plasma filtration adsorption (CPFA).
      METHODS: Thirteen critically ill patients (9 severely burned, 4 polytraumas) with
      septic shock and acute renal failure treated with CPFA-CVVHD by using bicarbonate
      based solutions (heparin-CPFA group, 58 sessions) or with CPFA-CVVHF using
      citrate (citrate-CPFA group, 36 sessions). RESULTS: Plasma flow and used
      cartridges showed no differences between the citrate-CPFA and heparin-CPFA
      groups, while lost clotted cartridges were significantly lower in the citrate
      CPFA group. Blood ionized calcium (iCa2+), Ca2+ infusion, pH and bicarbonates
      remained constant during citrate-CPFA, with no difference between pre- and post
      cartridge plasma citrate. A significant positive correlation between iCa2+ in
      blood and ultrafiltrate was present. CONCLUSIONS: These suits demonstrate the
      feasibility and safety of regional citrate anticoagulation in severely burned and
      polytrauma septic patients treated by CPFA.

PMID- 15256797
TI  - In vitro pharmacological inhibition of human vascular smooth muscle cell
      proliferation for the prevention of hemodialysis vascular access stenosis.
AB  - BACKGROUND: Vascular access for chronic hemodialysis often fails as a result of
      stenosis caused primarily by the proliferation of vascular smooth muscle cells
      (VSMC). Various drugs have been shown to inhibit the proliferation of VSMC under
      different conditions. METHODS: In this study, we compared the inhibitory effect
      of ten drugs on the proliferation of human aortic smooth muscle cells (SMC) in
      culture. Quiescent cells were cultured in the presence of growth factors, fetal
      bovine serum and incremental concentrations of the test drug. Cell proliferation
      was assessed by the MTT reduction assay. RESULTS: Aspirin, enalaprilat, heparin,
      hydroxyurea, indomethacin and tirofiban were ineffective. While dipyridamole,
      paclitaxel, tranilast and verapamil inhibited cell proliferation, the
      concentrations required were significantly higher than the clinical plasma levels
      achieved after systemic administration. CONCLUSION: Local delivery of these drugs
      to the target site may therefore be a more effective and appropriate strategy for
      the prevention of hemodialysis vascular access stenosis.

PMID- 15256799
TI  - A one-year trial of in-center daily hemodialysis with an emphasis on quality of
      life.
AB  - BACKGROUND/AIMS: Hemodialysis is associated with acute changes in several
      physiologic factors. Previous studies have suggested significant clinical and
      quality of life (QOL) benefits of daily hemodialysis (DHD) compared with 3 times
      weekly hemodialysis (CHD). We conducted a prospective trial to evaluate the
      effects of switching chronic hemodialysis patients to in-center DHD for a 12
      month period. METHODS: There were no exclusion criteria. Patients received
      hemodialysis 6 times per week. The study set a standardized weekly Kt/V (stdKt/V)
      goal of 3.0. A broad array of clinical parameters was determined. QOL was
      assessed with multiple instruments. RESULTS: Eleven subjects completed 12 months
      and 12 completed 6 months on DHD. Significant changes relative to baseline at 12
      months of DHD included decreased BP and improvements in QOL parameters by
      multiple techniques. 100% of patients at 12 months wished to continue DHD.
      CONCLUSIONS: DHD offers advantages over CHD with respect to improved QOL and BP
      control.

PMID- 15256800
TI  - Cerebral ultrasound findings in neonatal lupus syndrome.
AB  - A prospective study was performed enrolling 11 newborns with neonatal lupus
      syndrome (NLS) and 22 control newborns to investigate cerebral ultrasound (US)
      anomalies and their relationship with clinical neurological signs and laboratory
      findings. Cerebral US detected a significantly higher incidence in the study
      group of both subependymal pseudocysts (SEPC) and subependymal hemorrhage (SEH),
      neither of which correlated to autoantibody levels. All infants had completely
      normal neurological examinations both at birth and follow-up. The
      etiopathogenesis of central nervous system findings in NLS is discussed. US
      evaluation identified minimal anomalies compatible with favorable outcome:
      further studies are necessary to investigate the possible long-term sequelae,
      pathogenesis and spectrum of cerebral US findings.

PMID- 15256801
TI  - Gamma-tocopherol--an underestimated vitamin?
AB  - The main research activities of the last decades on tocopherols were mainly
      focused on alpha-tocopherol, in particular when considering the biological
      activities. However, recent studies have increased the knowledge on gamma
      tocopherol, which is the major form of vitamin E in the diet in the USA, but not
      in Europe. gamma-Tocopherol provides different antioxidant activities in food and
      in-vitro studies and showed higher activity in trapping lipophilic electrophiles
      and reactive nitrogen and oxygen species. The lower plasma levels of gamma-
      compared to alpha-tocopherol might be discussed in the light of different
      bioavailability, but also in a potential transformation from gamma- into alpha
      tocopherol. From the metabolism end product, only that of gamma-tocopherol (2,7,8
      trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman), but not that of alpha
      tocopherol, was identified to provide natriuretic activity. Studies also indicate
      that only the gamma-tocopherol plasma level served as biomarker for cancer and
      cardiovascular risk. Therefore, this paper provides a comprehensive review on
      gamma-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in
      food, different intake linking to different plasma levels in USA and Europe,
      absorption and metabolism, biological activities, and possible role in human
      health.

PMID- 15256802
TI  - Food consumption patterns in a mediterranean region: does the mediterranean diet
      still exist?
AB  - AIMS: To assess the food consumption patterns in the adult population of a
      Mediterranean region: the Balearic Islands (BI). METHODS: A cross-sectional
      nutritional survey was carried out in the BI between 1999 and 2000. A random
      sample (n = 1,200) of the adult population (16-65 years) was interviewed. Dietary
      habits were assessed by means of 24-hour recall during 2 non-consecutive days,
      the first in the warm season and the second in the cold season, and a
      quantitative food frequency questionnaire. Anthropometric measurements were also
      obtained. RESULTS: Current food patterns in the BI are characterized by a
      prominent consumption of dairy products, vegetables, fruit, bread, soft drinks
      and meat. According to the dietary guidelines for the Spanish population, only
      appropriate consumption of olive oil and other fats, dairy products, nuts, and
      soft drinks have been achieved. Intakes of fruit, vegetables, fish, eggs, pulses,
      cereals and potatoes are below desirable levels. On the other side, intakes of
      sugary products, sweets and cakes are higher than desirable. Alcohol intake, in
      the context of the Mediterranean diet, can be considered as acceptable.
      CONCLUSIONS: The dietary patterns observed among the BI population are in harmony
      with the actual dietary trends in Spain and other Mediterranean countries.
      Mediterranean dietary habits still exist, but a progressive departure from the
      traditional Mediterranean diet is being observed mainly in younger generations.
      It would be desirable to increase the consumption of fish, vegetables, fruit,
      cereals and pulses and decrease the intake of food sources containing saturated
      fat.

PMID- 15256803
TI  - Changes of fatty acid composition of human milk during the first month of
      lactation: a day-to-day approach in the first week.
AB  - BACKGROUND: Fatty acid composition of human milk (HM) is known to change
      considerably during lactation. However, we were unable to find data on changes of
      fatty acid composition of HM during the very early phase of lactation, i.e. in
      the first week of life. SUBJECTS AND METHODS: HM samples were obtained from 18
      healthy lactating women every day during the first week and thereafter on the
      14th and 28th days of lactation. Fatty acid composition of colostrum and mature
      HM samples was determined by high-resolution capillary gas-liquid chromatography.
      RESULTS: Values of the n-6 essential fatty acid, linoleic acid, in HM did not
      change significantly during the first month of lactation, whereas values of the n
      3 essential fatty acid, alpha-linolenic acid, showed significant increases during
      the first 2 weeks of lactation (1st day: 0.49 [0.12], % weight/weight, median
      [ranges from the 1st to the 3rd quartile], 14th day: 0.69 [0.31], p < 0.05). In
      contrast, values of the n-6 long-chain metabolites, eicosadienoic-, dihomo-gamma
      linolenic- and arachidonic acid, as well as the values of the n-3 long-chain
      metabolites, eicosatrienoic-, and eicosapentaenoic acid exhibited significant
      decreases during the entire period investigated. The principal n-3 long-chain
      metabolite, docosahexaenoic acid, showed a significant increase between the 3rd
      and 14th days, but a significant decrease between the 14th and 28th days (3rd
      day: 0.15 [0.13], 14th day: 0.28 [0.11], p < 0.05, 28th day: 0.19 [0.12], p <
      0.01). There were statistically significant positive correlations between
      arachidonic and docosahexaenoic acid values on the 1st (r = 0.67, p < 0.01), 5th
      (r = 0.56, p < 0.05) and the 6th (r = 0.53, p < 0.05) days of lactation.
      CONCLUSION: Fatty acid composition of HM changes significantly even during the
      first week of lactation. The lack of positive correlation between essential fatty
      acids and their long-chain metabolites suggests that it is not only the
      availability of essential fatty acids that influences the fatty acid composition
      of human colostrum.

PMID- 15256804
TI  - Induction sirolimus and delayed graft function after deceased donor kidney
      transplantation in the United States.
AB  - BACKGROUND/AIMS: Previous studies have reported a link between the use of
      induction sirolimus (INDSRL) and delayed graft function (DGF) after kidney
      transplantation. However, none have had sufficient power to adjust for all
      factors known to be associated with DGF. METHODS: We conducted a retrospective
      cohort study of US deceased donor kidney transplantation recipients in the United
      States Renal Data System (USRDS) from January 1, 2000 to May 31, 2001. Logistic
      regression analysis was used to model adjusted odds ratios (AOR) for the
      development of DGF, adjusted for other factors previously reported to be
      associated with DGF. RESULTS: Among 8,319 patients meeting inclusion criteria,
      361 patients received INDSRL, of whom 98 (27.1%) had DGF, compared to 22.5% among
      patients who did not receive INDSRL. In multivariate analysis, INDSRL was
      associated with an increased risk of DGF, with an adjusted odds ratio of 1.42
      (95% CI: 1.07-1.90). Other factors associated with DGF were similar to those
      previously reported. INDSRL was not significantly associated with graft loss at 1
      year in Cox regression. CONCLUSIONS: INDSRL was independently associated with DGF
      in US deceased donor kidney transplantation recipients, adjusted for all other
      factors previously shown to be associated with DGF.

PMID- 15256805
TI  - Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle
      cells.
AB  - BACKGROUND/AIMS: IL-6, an inducer of the acute-phase response, is linked with the
      development of vascular disease and atherosclerosis. One mechanism likely
      involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6
      can induce VSMC proliferation and the release of monocyte chemoattractant protein
      1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus
      activated kinase)/STAT (signal and transducers and activators of transcription)
      signaling pathway. METHODS: Rat VSMC were stimulated with IL-6 in the presence or
      absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1
      (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) was determined.
      RESULTS: IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time
      dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1
      protein production and DNA synthesis dose dependently. 50 microM of AG490, a
      specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1
      production, with near complete inhibition of DNA synthesis. CONCLUSION: The
      JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA
      synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in
      the development of vascular disease and atherosclerosis.

PMID- 15256806
TI  - Diagnosis, treatment and outcome of pancreatoblastoma.
AB  - BACKGROUND: Pancreatoblastoma is a rare tumour mainly presenting in childhood but
      also in adults. OBJECTIVES: The aim was to determine the clinical course of
      pancreatoblastoma by an analysis of reported cases. METHODS: Patients with
      pancreatoblastoma were identified from Medline and combined with patients
      identified from the Royal Liverpool University Hospital. RESULTS: There were 153
      patients with a median (range) age at presentation of 5 (0-68) years and a
      male:female ratio of 1.14:1. The most frequent site was the head of pancreas
      (48/123, 39%). The median and 5-year (95% CI) survival rates were 48 months and
      50% (37-62%) respectively. At presentation there were 17 (17%) out of 101
      patients with metastases, the liver being the commonest site (15/17, 88%). On
      univariate analysis, factors associated with a worse prognosis were synchronous
      (p = 0.05) or metachronous metastases (p < 0.001), non-resectable disease at
      presentation (p < 0.001) and age > 16 years at time of presentation (p = 0.02).
      On multivariate analysis, resection (p = 0.006) and metastases post-resection (p
      = 0.001) but not local recurrence influenced survival. CONCLUSIONS:
      Pancreatoblastoma is one of the pancreatic tumours with a relatively good
      prognosis. The treatment of choice is complete resection with long-term follow-up
      aiming to treat any early local recurrence or metastasis.

PMID- 15256807
TI  - Expression of CD24 in adenocarcinomas of the pancreas correlates with higher
      tumor grades.
AB  - BACKGROUND/AIMS: CD24 is expressed in hematological malignancies as well as in a
      large variety of solid tumors and is often associated with a more aggressive
      course of the disease. We aimed to evaluate CD24 protein expression in pancreatic
      adenocarcinomas and to correlate it to clinicopathological data including patient
      survival. METHODS: 95 primary adenocarcinomas of the pancreas were immunostained
      using a monoclonal CD24 antibody (Ab-2, clone 24C02). Staining was evaluated as
      negative versus positive for statistical analysis. RESULTS: CD24 expression was
      observed in 71.6% of cases with a heterogeneous distribution, and a significantly
      higher rate of positivity in high grade (G3) tumors. In univariate survival
      analyses, no association of CD24 expression with shortened overall survival of
      the patients could be demonstrated. CONCLUSION: CD24 is commonly expressed in
      adenocarcinomas of the pancreas, preferentially high-grade tumors and thus might
      be a marker of disease progression.

PMID- 15256808
TI  - Dose-response effects of estrogen and tamoxifen upon methamphetamine-induced
      behavioral responses and neurotoxicity of the nigrostriatal dopaminergic system
      in female mice.
AB  - In the present experiment we evaluated the dose-response effects of estrogen
      (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral
      and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic
      (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1-40
      microg resulted in a neuroprotective effect upon the NSDA system as defined by
      both a preservation of striatal dopamine (DA) concentrations and a decrease in
      DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-microg EB
      dose occurred in the absence of any statistically significant effect upon the
      bioassay parameter of uterine weight. With the exception of an increase in
      stereotypy time as a response to the 40-microg dose, EB at any of the doses
      tested failed to alter any acute behavioral responses evoked by MA. In response
      to TMX, a statistically significant NSDA neuroprotectant response was obtained
      for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500
      microg. No statistically significant effects upon uterine weights were obtained
      for any of the doses of TMX tested. Behaviorally, TMX at 500 microg had the
      effect of increasing the amount of time spent in the center of the cage. Taken
      together these results demonstrate: (1) EB and TMX at relatively low doses can
      exert a neuroprotective effect against MA; (2) these neuroprotective effects of
      EB and TMX can occur in the absence of an effect upon the bioassay parameter-
      uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more
      sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX
      upon acute behavioral responses of the NSDA system to MA can be distinguished
      from their neuroprotective actions.

PMID- 15256809
TI  - Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and
      reverses fasting-induced c-Fos expression.
AB  - The hypothalamic arcuate nucleus (Arc) monitors and integrates hormonal and
      metabolic signals involved in the maintenance of energy homeostasis. The
      orexigenic peptide ghrelin is secreted from the stomach during negative status of
      energy intake and directly activates neurons of the medial arcuate nucleus (ArcM)
      in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from
      the gut and reduces food intake when applied peripherally. Neurons in the ArcM
      express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit
      feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular
      recordings, we (1) characterized the effects of PYY on the electrical activity of
      ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect
      of PYY on neuronal activity with the energy status, we (2) investigated the
      ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of
      mice. In addition, we (3) sought to confirm that PYY reduces food intake under
      our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all
      ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was
      dose-dependent and occurred at a threshold concentration of 10(-8)M. Consistent
      with the opposite effects of ghrelin and PYY on food intake, a high percentage
      (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with
      this inhibitory action, peripherally injected PYY partly reversed the fasting
      induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food
      deprived mice reversed the fasting-induced activation in the Arc. Furthermore,
      peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the
      activity of Arc neurons correlated with the feeding status and was not only
      reduced by feeding but also by administration of PYY in non-refed mice. In
      conclusion, our current observations suggest that PYY may contribute to signaling
      a positive status of energy intake by inhibiting Arc neurons, which are activated
      under a negative status of energy intake by signals such as ghrelin.

PMID- 15256810
TI  - Galanin-like peptide mRNA alterations in arcuate nucleus and neural lobe of
      streptozotocin-diabetic and obese zucker rats. Further evidence for leptin
      dependent and independent regulation.
AB  - Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural
      similarities to galanin and a high affinity for galanin receptors. GALP is
      expressed by a discrete population of neurons in the arcuate nucleus (ARC) and
      median eminence of the hypothalamus of several species, including the rat. GALP
      neurons express leptin receptors and GALP mRNA levels are decreased slightly in
      fasted rats and stimulated significantly by acute leptin treatment in combination
      with fasting. In studies to further explore the leptin dependence of GALP
      expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and
      streptozotocin-induced diabetic (STZ-DM) rats. In leptin receptor-deficient obese
      Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels
      in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were
      increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. In
      hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower
      body weight than controls, GALP mRNA levels in the ARC were decreased by 90%,
      while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). GALP is also
      expressed by pituicytes in the neural lobe of the rat pituitary gland and GALP
      expression is increased by osmotic stimulation such as dehydration and salt
      loading. Thus, in STZ-DM rats that are in a hyperosmotic state with elevated
      plasma vasopressin levels, GALP mRNA levels were increased by approximately 20
      fold in the neural lobe relative to control (n = 4, p < 0.001). The current
      findings are consistent with a strong tonic influence of leptin receptor
      signalling on hypothalamic GALP expression under normal conditions, and possible
      abnormalities in GALP neuronal signalling and their putative targets, thyrotropin
      releasing hormone and gonadotropin hormone-releasing hormone neurons, under
      pathophysiological conditions such as diabetes and obesity. Our data in STZ-DM
      rats also clearly demonstrate that GALP gene expression is differentially
      regulated in neurons and pituicytes.

PMID- 15256811
TI  - N-acetylcysteine in the prevention of radiocontrast-induced nephropathy: clinical
      trials and end points.
AB  - N-acetylcysteine (NAC) has been suggested to prevent radiocontrast-induced
      nephropathy (RCIN) in patients with a reduced renal function. However, clinical
      studies have not been demonstrating this effect consistently. Also, reviews and
      meta-analyses dealing with the question of prevention of RCIN by NAC have been
      controversial. Nearly all investigators used serum creatinine as surrogate end
      point of their trials, and changes in serum creatinine concentrations are thought
      to reflect the extent of renal injury as primary outcome. In a recent study, an
      effect of NAC on creatinine values and estimated glomerular filtration rate
      without any effect on cystatin C levels has been shown in volunteers with a
      normal renal function. Therefore, before renal protective effects of NAC in RCIN
      are proposed, any direct effects of NAC on creatinine, urea, and estimated
      glomerular filtration rate should be addressed. In future trials, the glomerular
      filtration rate should preferentially be measured directly, or at least
      additional markers of the renal function (e.g., serum cystatin C) have to be
      assessed. Furthermore, additional 'hard' end points, i.e., hospital morbidity,
      mortality, or dialysis dependency, should be considered in the design of future
      studies of RCIN.

PMID- 15256812
TI  - Free reactive oxygen species and nephrotoxicity of contrast agents.
AB  - BACKGROUND: The nephrotoxicity induced by contrast media remains a serious
      clinical problem, and the underlying mechanism has not been completely
      understood. Experimental and clinical investigations suggest that reactive oxygen
      species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and
      that antioxidants can prevent this damage. METHODS: Cultured human proximal renal
      tubule cells (HK-2) were exposed to hydrogen peroxide (H2O2) at different
      concentrations. H2O2-induced tubular DNA damage was examined in the presence of
      the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA
      damage was measured with the alkaline comet assay (single cell gel
      electrophoresis). We also studied 12 patients with stable renal impairment
      (median baseline creatinine 296 micromol/l; range: 203-495 micromol/l) undergoing
      cardiac catheterization/intervention prospectively. Patients received 800 mg
      MESNA intravenously 30 min before exposure to the contrast agent in addition to
      0.9% saline hydration. RESULTS: In the cell cultures, oxidative stress on HK-2
      cells induced increased DNA migration in the comet assay. Treatment of tubular
      cells with the antioxidant MESNA prior to the addition of H2O2 significantly
      reduced DNA migration in the comet assay. In the clinical study, treatment of the
      patients with MESNA prevented the adverse renal effect of contrast media (median
      serum creatinine 293; range: 187-433 micromol/l) 48 h after coronary
      angiography/intervention. CONCLUSION: Both the in vivo and the in vitro studies
      suggest that the ROS-mediated renal injury could be inhibited by a potent
      antioxidant such as MESNA.

PMID- 15256814
TI  - Impact of different immunosuppressive regimens on antigen-presenting blood cells
      in kidney transplant patients.
AB  - BACKGROUND: Alloantigen-specific and unspecific immune processes contribute to
      chronic renal graft dysfunction. Despite 'optimized immunosuppressive therapy'
      (IS), the role of chronic cell activation still remains open. METHODS: 69 kidney
      transplant recipients (NTX) were assessed for monocyte surface antigens CD14 (LPS
      receptor) and CD16 (Fc-gamma-III receptor) by flow cytometry including the
      percentage amount of the proinflammatory CD14+CD16+ subset. 14 non-dialysis
      patients with chronic renal failure (CRF) and 24 healthy persons served as
      controls. RESULTS: All 14 patients suffering from CRF revealed higher CRP serum
      levels compared to healthy controls (p = 0.01). NTX patients had a (not
      significant) tendency to higher CRP concentrations (p > 0.05). The mean
      expression of CD14 on monocytes (mCD14) was lower in patients with CRF and in NTX
      patients (p = 0.024-p = 0.026). NTX patients revealed low expression of monocytic
      CD14 with no difference between the single IS therapy groups. The proinflammatory
      monocyte subpopulation positive for CD14 and CD16 was elevated both in uremic and
      NTX patients (p < 0.002), despite long-lasting IS therapy. CONCLUSIONS:
      Continuing IS therapy, even under 'optimized' drug-monitoring conditions, does
      not sufficiently prevent or suppress a microinflammatory (and potential fibrotic
      growth-promoting) status in NTX patients.

PMID- 15256813
TI  - New AUC-based method to estimate drug fraction removed by hemodialysis.
AB  - BACKGROUND: A supplemental dose is often necessary after hemodialysis depending
      on the amount of drug removed by hemodialysis. However, there are different
      methods of estimating this amount, and most methods ignore drug rebound after
      hemodialysis. In this report we present a new area under the concentration curve
      (AUC)-based method that provides an estimate of the drug fraction removed by
      hemodialysis including drug rebound. METHODS: Valganciclovir, the oral prodrug of
      ganciclovir, was administered to 6 patients with end-stage renal disease.
      Hemodialysis was performed after 32 h. The fraction of ganciclovir removed by
      hemodialysis was estimated using the new AUC-based method, a classical method
      (using the slope on and off hemodialysis), the back-extrapolation method, and a
      reference model (a two-compartment model with zero-order input and first-order
      elimination). RESULTS: The AUC-based method and the back-extrapolation method
      provided accurate estimates of the fraction of ganciclovir removed by
      hemodialysis (47 +/- 6 and 46 +/- 5%, respectively) compared to the reference
      model (49 +/- 3%). The classical method, which does not account for the rebound
      of ganciclovir concentrations after hemodialysis, overestimated the removed
      fraction by 9% (58 +/- 3%). CONCLUSIONS: The new AUC-based method and the back
      extrapolation method accurately estimate the drug fraction removed by
      hemodialysis for drugs with a rebound after hemodialysis. The AUC-based method is
      more robust and as efficient compared to the back-extrapolation method.

PMID- 15256816
TI  - Sirolimus dosage during and after conversion from calcineurin inhibitor therapy
      to sirolimus in chronic kidney transplant patients.
AB  - Sirolimus (SRL) is an alternative to calcineurin inhibitors (CNI) in kidney
      transplant patients with chronic allograft dysfunction. METHODS: 33 patients were
      converted to SRL receiving a single loading dose of 15 mg and initial maintenance
      dose of 5 mg/day. CNI was reduced by 50% on day 1 and tapered during 4-6 weeks
      after achieving SRL target (8-12 ng/ml). Concomitant immunosuppressive therapy
      remained unchanged. RESULTS: Patient survival was 100% and graft survival was 85%
      after 1 year. Mean SRL dose decreased from 5 mg/day initially to 2.8 +/- 1.3
      mg/day. SRL dose-adjusted trough concentration did not change significantly over
      time. Dose-adjusted trough concentrations of CNI before conversion and of SRL
      after 1 year did not correlate. We observed no severe infections, however, one
      rejection Banff Ia occurred 7 months after conversion associated with
      subtherapeutic SRL trough concentration. Adverse events were anemia,
      dyslipidemia, epistaxis, stomatitis, and bronchiolitis obliterans which occurred
      mainly during the conversion phase. CONCLUSION: Overlapping conversion from CNI
      to SRL in chronic kidney transplant patients is possible and safe. However,
      further studies are necessary with shorter overlap and lower SRL loading and
      initial maintenance dose which might lead to a decrease in the high number of
      adverse events in the overlap phase.

PMID- 15256815
TI  - Low-dose sirolimus in combination with mycophenolate mofetil improves kidney
      graft function late after renal transplantation and suggests pharmacokinetic
      interaction of both immunosuppressive drugs.
AB  - AIMS: Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are
      common problems after organ transplantation. The aim of this study was to examine
      the safety and efficacy of switching from a calcineurin inhibitor-based to a
      calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and
      mycophenolate mofetil (MMF) late after renal transplantation. METHODS: Kidney
      biopsies were performed in renal-transplanted patients with increasing serum
      creatinine levels at least 6 months after transplantation (mean time +/- SD after
      renal transplantation: 76.4 +/- 50.4 months). Patients with no signs of acute
      rejection were switched to MMF (500-2,000 mg/day) in combination with a low dose
      of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of
      sirolimus and MMF, and blood pressure were monitored. RESULTS: 13 patients were
      investigated. During our observation period (mean observation time +/- SD: 11.2
      +/- 5.9 months), an improvement in renal function was observed in 10/13 patients.
      In 3/13 patients, renal function deteriorated further and hemodialysis was
      initiated in 2 patients within the next 6 months. However, a serum creatinine
      concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the
      switch of the immunosuppressive protocol. Administration of a low dosis of
      sirolimus (1 mg/day) led to relevant sirolimus (4.16 +/- 1.85 ng/ml) and MMF
      blood trough levels (month 1: 6.8 +/- 3.46; month 3: 4.67 +/- 1.78 mg/l). The
      following adverse events were observed: borderline acute rejection (1/11
      patients), anemia responding to higher dosage of erythropoietin (3/11),
      hyperlipidemia (1/11), and urinary tract infections (4/11). CONCLUSIONS: Low-dose
      sirolimus therapy in combination with concentration-adjusted MMF therapy leads to
      improvement of organ function late after renal transplantation. The follow-up of
      those patients should include assessments of blood cell counts, serum lipids and
      urinalysis to recognize the possible side effects.

PMID- 15256817
TI  - Effects of parathyroidectomy on renal allograft survival.
AB  - BACKGROUND: Hyperparathyroidism is a common problem secondary to renal
      insufficiency and is often not entirely resolved after renal transplantation
      (TX). METHODS: In this retrospective analysis, the effects of parathyroidectomy
      (PTX) on allograft function were evaluated and the risk factors involved in
      allograft deterioration in patients after PTX will be discussed. RESULTS: The
      rise in creatinine was steeper 1 year after PTX compared to 2 years before PTX in
      the majority (13 of 22) of patients. Compared to a cohort without PTX, graft
      survival was significantly decreased by 60% in 6 years (p < 0.0001). After
      multivariate adjustment, risk factors attributed to graft function included
      baseline creatinine (p = 0.02), baseline systolic blood pressure (p = 0.04) and
      time between TX and PTX, but not PTX itself. The peri-PTX drop in serum calcium
      was significantly more accentuated in patients exhibiting a worsening of graft
      function after PTX (p = 0.04). CONCLUSIONS: In patients requiring PTX, graft
      function is in danger of worsening. Since many factors contribute to this
      negative correlation and no association with parathyroid hormone (PTH) levels
      before PTX has been observed, we do not recommend prophylactic PTX on the basis
      of PTH levels only. However, appropriate management of peri-PTX risk factors is
      highly important. If the clinical situation, e.g. progressive renal
      osteodystrophy, requires removal of parathyroid glands, the procedure should be
      performed, if possible, in the presence of stable graft function.

PMID- 15256818
TI  - One for all--a multi-use dialysis system for effective treatment of severe
      thallium intoxication.
AB  - Guided by the idea of providing a stable electrolyte composition of the
      dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the
      advantages of a closed tank hemodialysis system with the efficacy and
      bacteriological safety of a single-pass system. Several thousand dialysis
      sessions have been performed with this system in the chronic hemodialysis
      population. Recently, highly efficient (i.e. high volume) dialysis systems have
      been successfully introduced for the treatment of critically ill patients in the
      intensive care unit as extended dialysis. Furthermore, they can also be a safer,
      more effective and less costly alternative to traditional extracorporeal
      techniques in the treatment of severe intoxication. In a case-based approach, we
      review the increasing use of such a system.

PMID- 15256819
TI  - Lithium acetate therapy in a maintenance hemodialysis patient.
AB  - BACKGROUND/AIMS: Single cases of lithium carbonate dosing in hemodialysis
      patients have been published. We investigate the dose-serum level relationship
      after single and multiple lithium acetate dosing in a hemodialysis patient and
      review the literature. METHODS: Lithium acetate was administered orally over a
      period of 11 months in a patient with major depressive episodes after being
      placed on hemodialysis three times a week. The serum trough levels of lithium
      before and after hemodialysis were analyzed. The data were compared with those
      reported in the literature, and potential drug interactions and the importance of
      the residual renal function are discussed. RESULTS: No adverse events due to the
      lithium therapy were documented. Steady state levels of between 0.6 and 0.8
      mmol/l of lithium acetate were achieved 17 days after initiating the therapy,
      using 24 mmol/l of lithium three times a week, in a patient with a residual
      diuresis of about 400 ml/day. In contrast, data reported in the literature
      implicate that only 9.6-14.4 mmol/l of lithium (450-600 mg of lithium carbonate)
      is sufficient to achieve adequate serum levels. CONCLUSIONS: The residual renal
      function can be important for lithium clearance. The creatinine clearance does
      not reflect this point.

PMID- 15256820
TI  - Cortisol and its relation to insulin resistance before and after weight loss in
      obese children.
AB  - BACKGROUND: Insulin resistance occurs both in obesity and in Cushing's syndrome
      suggesting a pathogenetic role of cortisol in insulin-resistant obese subjects.
      METHODS: We examined serum cortisol in 81 insulin-resistant (homeostasis model
      assessment (HOMA) >4) obese children (age in median 12 years) and 151 obese
      children without insulin resistance (HOMA < or = 4) (age in median 10 years) and
      compared these to cortisol of 83 healthy children of normal weight (age in median
      12 years). Multivariate linear regression analysis was conducted for the
      dependent variable insulin resistance (HOMA), including weight status (BMI), age,
      gender, pubertal stage and cortisol concentration as independent variables.
      Furthermore, we analyzed cortisol and insulin resistance in 45 obese children
      with significant weight loss (reduction in SDS-BMI > or = 0.5) and in 109 obese
      children without significant weight loss (reduction in SDS-BMI <0.5) over the
      time period of 1 year. RESULTS: Cortisol was significantly (p = 0.006) higher in
      obese insulin-resistant children (median 14.6 microg/dl) compared to those of
      normal weight (median 11.4 microg/dl) or obese without insulin resistance (median
      11.7 microg/dl). Insulin resistance was significantly influenced by weight status
      (BMI), age and cortisol using multivariate linear regression analysis. A
      reduction in overweight showed a significant decrease in cortisol (p = 0.005) and
      insulin resistance (p = 0.002) in insulin-resistant children, whilst there were
      no significant changes in children not reducing their overweight and in non
      insulin-resistant children. CONCLUSIONS: Cortisol was moderately increased in
      insulin-resistant, obese children and related to insulin resistance. Weight
      reduction led to a decrease in cortisol and insulin resistance. These facts point
      to an association between cortisol and insulin resistance in obesity.

PMID- 15256821
TI  - Short stature with normal growth hormone stimulation testing: lack of evidence
      for partial growth hormone deficiency or insensitivity.
AB  - OBJECTIVES: To test the hypothesis that children with short stature and peak
      stimulated GH (pGH) of 7-10 microg/l have partial GH deficiency and to test the
      hypothesis that short children with normal pGH but low IGF-I levels have partial
      GH deficiency or partial GH insensitivity. DESIGN AND PATIENTS: Retrospective
      analysis of the clinical and biochemical profiles of 76 children who underwent an
      evaluation for short stature (height < 5th percentile) that included two, sex
      steroid-primed GH stimulation tests. RESULTS: Patients with pGH < 7 microg/l (n =
      14) differed significantly from those with pGH > 7 microg/l (n = 62), having
      greater midparental height (MPH) SDS, a greater disparity between height SDS and
      MPH SDS, and lower IGF-I SDS. Patients with pGH of 7-10 microg/l (n = 12) did not
      have characteristics intermediate between those with pGH < 7 microg/l and those
      with pGH > or = 10 microg/l, but instead resembled those with pGH > or = 10
      microg/l. Patients with pGH > or = 7 microg/l, but low IGF-I (< -2 SDS) (n = 5),
      did not show characteristics intermediate between those with pGH < 7 microg/l and
      those with pGH > or = 7 microg/l and normal IGF-I. CONCLUSIONS: These data do not
      support either the hypothesis that children with pGH of 7-10 microg/l have
      partial GH deficiency or the hypothesis that children with normal pGH but
      subnormal IGF-I levels have partial GH deficiency or insensitivity.

PMID- 15256822
TI  - Relevance of lunar periodicity in human spontaneous abortions.
AB  - The effect of the moon on human reproduction has been scarcely investigated and
      with controversial results. The present analysis describes a significant effect
      of extreme perigeal lunar positions on the number of hospitalized spontaneous
      abortions (n = 1,329) recorded at two university clinics and a public hospital at
      Padova, Italy, during the years 2000-2003. Spectral analysis evidenced a 205-day
      period which appears to be correlated with the 206-day periodicity in extreme
      lunar distances. Circa-septan and circa-annual periodicities were also observed.
      Peak significances were determined by a Monte Carlo approach (circa-septan and
      205-day periodicities: p < 0.001; circa-annual periodicity: p < 0.05). Our study
      indicates that the occurrence of human abortions displays suggestive
      periodicities that may be of relevance for gynecological and obstetrical
      practice.

PMID- 15256823
TI  - Peritoneal closure vs. non-closure: estimation of pelvic fluid by transvaginal
      ultrasonography after abdominal hysterectomy.
AB  - OBJECTIVE: To determine the volume of pelvic fluid and febrile morbidity after
      hysterectomy in which the peritoneum was or was not closed. DESIGN: Prospective
      single-center study. PARTICIPANTS: Fifty-four women undergoing abdominal
      hysterectomy were enrolled in the study. Patients were randomized into two groups
      according to peritoneal closure: group I (n = 28) in which the peritoneum was
      closed, and group II (n = 26) in which the peritoneum was left open. All
      participants had early postoperative transvaginal ultrasound. OUTCOME MEASURES:
      Volume of pelvic fluid accumulated after hysterectomy, total leukocytic count
      before and after hysterectomy, body temperature over the first 24 h, and wound
      healing. RESULTS: There was a statistically significant difference between both
      groups regarding the volume of pelvic fluid collection, the duration of the
      operation and number of ampoules needed (p < 0.05). There was no statistically
      significant difference regarding body temperature, TLC, and wound complications.
      CONCLUSION: Peritoneal non-closure does not increase short-term morbidity,
      however it does cause an increase in peritoneal pelvic fluid. The impact of this
      on long-term sequelae as adhesions should be investigated.

PMID- 15256824
TI  - Idarubicin administered during pregnancy: its effects on the fetus.
AB  - Acute myeloblastic leukemia, subtype M1, was diagnosed in a 39-year-old G2P1
      Japanese woman at 21 weeks' gestation. Remission-induction polychemotherapy,
      including daunorubicin, performed for one cycle, did not lead to remission.
      Second-line chemotherapy, including idarubicin, performed for one cycle, was
      administrated during the early third trimester of pregnancy. Septic shock
      occurred due to severe myelosuppression. An emergent cesarean section was
      performed in response to a nonreassuring pattern of the fetal heart rate and a
      rapid decrease in fetal amniotic fluid. The neonate delivered at 32 weeks'
      gestation showed no signs of cardiac failure but did show signs of transient
      myelosuppression, hepatopathy, and elevated creatine kinase. Complete remission
      was established with idarubicin including chemotherapy.

PMID- 15256826
TI  - Myofascial pain, fibromyalgia or fibrositis?
AB  - The terms myofascial pain, fibromyalgia and fibrositis are critically examined.
      They constitute diagnostic labels for non-specific musculoskeletal aches and
      pains. Analysis of the evidence shows that none of these labels is substantiated
      by hard physical signs or by laboratory evidence of consistent pathological or
      biochemical abnormality. What is the objective evidence for disorder(s) of
      muscle, fascia or fibrous tissues, so clearly indicated by these diagnostic
      names? Alternative terms such as 'regional pain syndrome' or 'chronic pain
      syndrome' merely redefine the clinical problem without providing a mechanism or
      basis for diagnosis. Despite different diagnostic criteria, these conditions,
      along with chronic fatigue syndrome, have many demographic and clinical
      similarities, most notably tender trigger points. Indeed, the terms are often
      used interchangeably. There are few differences in the symptoms, physical
      findings, laboratory tests, functional status, psychosocial features and
      psychiatric disorders. This paper seeks not to deny the existence of aches and
      pains, but to critically examine the utility of these terms. The only claimed
      physical sign is the presence of tender trigger points over muscles or muscle
      attachments. Research suggests that tender points are a measure of general
      distress related to pain complaints but separately associated with fatigue and
      depression. They are present in some normal subjects and are variable in
      occurrence in time in the same individual. They reflect no demonstrable
      pathology. It is therefore argued that none of these commonly used diagnoses
      represent distinct disease entities. A possible but unproven alternative
      hypothesis is that such symptoms relate to neural pain with both peripheral and
      central components, and in some instances psychological or wilful embellishment.

PMID- 15256825
TI  - Increased frequency of bacterial vaginosis and Chlamydia trachomatis in pregnant
      women with human papillomavirus infection.
AB  - The aim of this study was to verify the presence of bacterial vaginosis (BV),
      Candida sp, Chlamydia trachomatis, Neisseria gonorrhoeae, to determine the
      prevalence of tobacco use and measure vaginal pH (VpH) in pregnant women with (n
      = 26) and without (n = 26) human papillomavirus (HPV) infection, and make
      comparisons between these 2 groups. HPV, C. trachomatis and N. gonorrhoeae were
      diagnosed using hybrid capture, BV using clinical criteria, and Candida sp via
      cultures. A digital pH meter was used to measure VpH. The frequencies of Candida
      sp were 19.2 and 23.1% (p = 1), and VpH was 4.4 +/- 0.4 and 4.3 +/- 0.4 (p =
      0.23), in the HPV-positive and HPV-negative groups, respectively. Compared to the
      group of pregnant women without HPV infection, those with HPV infection had a
      significantly higher prevalence of tobacco use (50 vs. 11.5%; p = 0.006), BV
      (53.8 vs. 15.4%; p = 0.007), and C. trachomatis (34.6 vs. 7.7%; p = 0.039). No
      case of N. gonorrhoeae was diagnosed. All cases of C. trachomatis and BV had high
      grade HPV infection.

PMID- 15256828
TI  - White matter loss in the splenium of the corpus callosum in a case of posterior
      cortical atrophy: a diffusion tensor imaging study.
AB  - There have been several functional imaging studies using PET and SPECT to
      investigate posterior cortical atrophy (PCA). These studies have suggested
      dysfunction of corticocortical connections which is consistent with the
      occipitoparietal stream. However, there are no reports suggesting disturbance of
      the white matter that interconnects the temporal, parietal and occipital
      cortices. We measured fractional anisotropy (FA) in the genu and splenium of the
      corpus callosum and created color maps using diffusion tensor imaging (DTI),
      which is a relatively new MRI technique that allows visualization of the
      directionality of water diffusion, in a patient with PCA and compared these
      findings with those in 5 typical Alzheimer disease (AD) patients. The PCA patient
      was a 75-year-old man presenting with progressive complex visual disorder who
      satisfied the clinical diagnostic criteria for PCA. In 5 typical AD patients, the
      FA index in the splenium was higher than that in the genu; however, in the PCA
      patient, the FA index in the splenium was significantly lower than that in the
      genu. A DTI-based color map of the PCA patient showed reduction of anisotropy and
      fiber volume in the splenium. These findings suggest that the splenium of the
      corpus callosum secondarily degenerated due to neuronal degeneration of the
      temporal, parietal and occipital cortices and suggest that reduction of the FA in
      the splenium is one of the characteristics of PCA.

PMID- 15256827
TI  - Normal CSF hypocretin-1 (orexin A) levels in dementia with Lewy bodies associated
      with excessive daytime sleepiness.
AB  - Excessive daytime sleepiness, hallucinations and REM sleep behavior disorder are
      symptoms reported in both dementia with Lewy bodies (DLB) and narcolepsy.
      Considering the demonstration of low hypocretin-1/orexin A levels in the
      cerebrospinal fluid (CSF) of most patients with narcolepsy, we hypothesized the
      presence of a deficient hypocretinergic transmission in DLB. Hypocretin-1 was
      tested in the CSF of 10 DLB patients. Levels were found to be in the normal range
      (mean 521 pg/ml, range 382-667) when compared to controls (n = 20, mean 497
      pg/ml, range 350-603) and Alzheimer's disease patients (n = 7, mean 474 pg/ml,
      range 333-564). In DLB, excessive daytime sleepiness, hallucinations and REM
      sleep behavior may occur in the absence of a detectable hypocretin deficiency.

PMID- 15256829
TI  - Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD
      questionnaire ReQuest.
AB  - BACKGROUND/AIMS: The changes in gastroesophageal reflux disease (GERD)-related
      symptoms on treatment are variously described, but currently available
      questionnaires have shortcomings. We therefore developed a self-assessment reflux
      questionnaire (ReQuest). This article describes the process of development and
      testing. MATERIALS AND METHODS: For the first version of ReQuest the symptom
      spectrum of GERD and the various symptom descriptions were investigated. The 67
      identified symptom descriptions were condensed empirically into 6 dimensions, to
      which a 7th dimension on general well-being was added. The symptom burden of the
      dimensions was measured by frequency and/or intensity. ReQuest was translated
      into different languages and then tested in focus groups. The initial validation
      was based on data from a clinical trial of patients with erosive GERD, treated
      with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the
      contribution of each symptom to the different dimensions. Additionally,
      correlation analyses between the identified factors and the dimensions were
      performed. RESULTS: On the basis of factor analyses, ReQuest was reduced to a 60
      item scale. The factors generated correlated strongly with the dimensions and
      confirmed the empirical process mathematically. CONCLUSION: ReQuest provides a
      valuable, self-assessment tool for evaluating the daily treatment response in
      patients with erosive GERD.

PMID- 15256830
TI  - Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and
      validation of the new questionnaire ReQuest in erosive GERD.
AB  - BACKGROUND/AIMS: Evaluation of the response of gastroesophageal reflux disease
      (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and
      responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux
      Questionnaire (ReQuest). This publication describes the psychometric evaluation
      and validation of ReQuest. METHODS: This second phase of development was based on
      data from a clinical trial of patients with erosive GERD who received
      pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and
      daily the short version of ReQuest. The psychometric analyses of ReQuest included
      internal consistency, test-retest reliability and responsiveness. Construct
      validity was evaluated by comparison with the Gastrointestinal Symptom Rating
      Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. RESULTS:
      Validation of ReQuest indicated very high internal consistency (Cronbach's alpha
      = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94
      (long-long) and 0.86 (short-short)). This was also the case for the two subscales
      ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81.
      Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct
      validity was good. CONCLUSION: ReQuest is a highly reliable, valid and responsive
      self-assessment tool for evaluating treatment response in patients with erosive
      GERD, and can be applied daily.

PMID- 15256831
TI  - Differential expression of connective tissue growth factor in inflammatory bowel
      disease.
AB  - Inflammatory bowel disease consists of Crohn's disease (CD) and ulcerative
      colitis (UC). A major clinical problem in some patients is to differentiate
      clearly between these entities, which is important when planning appropriate
      medical and surgical treatment. Connective tissue growth factor (CTGF), a novel
      peptide involved in fibrotic disorders, was analyzed in the present study in CD
      and UC patients to evaluate its possible role in these two disorders. Twenty-five
      normal human intestinal tissue samples were obtained through an organ donor
      program. CD tissues were obtained from 28 individuals undergoing partial
      intestinal resection (17 small bowel; 11 large bowel) due to complications of the
      disease. UC tissue samples were obtained from 16 patients undergoing colectomy
      due to complications of the disease. Expression of CTGF was studied by Northern
      blot analysis. In situ hybridization was used to localize mRNA moieties in the
      tissue samples. Northern blot analysis revealed an average 5-fold increase in
      CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with
      normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were
      comparable to those of normal controls. However, UC tissue samples exhibited
      enhanced TGF-beta1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD
      samples showed CTGF mRNA localized especially in fibroblasts within the
      submucosal layer, around lymph follicles and in some areas of intense damage in
      the proximity of the luminal surface, whereas inflammatory cells were devoid of
      any CTGF mRNA signal. The present data indicate that CTGF plays a different role
      in IBD and might be useful, especially in those cases with unusual disease
      presentation, to better differentiate UC and CD. In addition, our data indicate a
      crucial role for CTGF in CD, where fibrosis and stenosis are frequent
      complications that require surgery.

PMID- 15256832
TI  - Quality of life and illness costs in irritable bowel syndrome.
AB  - Quality of life is reduced in patients with irritable bowel syndrome, and the
      costs for this disease are substantial to society. During a meeting in London,
      UK, the IBiS club reviewed the literature on these subjects. Drawbacks and
      advantages with existing instruments to assess quality of life and costs were
      discussed and the clinical and scientific relevance of the current knowledge was
      assessed. A summary from the meeting is presented in this paper.

PMID- 15256833
TI  - Granulocytic sarcoma of the colon and leukemic infiltration of the liver in a
      patient presenting with hematochezia and jaundice.
AB  - Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature cells
      of the granulocytic series known to occur in patients with myelodysplastic
      syndrome, chronic myelogenous leukemia, or acute myelogenous leukemia (AML).
      Involvement of the gastrointestinal tract is relatively rare in GS. We present an
      extremely rare case of GS of the colon and liver infiltration in a 60-year-old
      male patient with AML presenting with jaundice and hematochezia and review the
      literature. It should be kept in mind that hematochezia may be due to colonic
      involvement of GS besides thrombocytopenia which is usually encountered in
      patients with AML.

PMID- 15256834
TI  - Specific functional effects of memantine treatment in patients with moderate to
      severe Alzheimer's disease.
AB  - Treatment of Alzheimer's disease (AD) that combats progressive functional
      deterioration can improve the patient's quality of life and reduce caregiver
      burden. Memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist,
      reduces global deterioration in AD patients and provides cognitive and functional
      benefits relative to placebo. Two previous studies reported statistically
      significant benefits of memantine for overall functional ability on the Alzheimer
      Disease Cooperative Study Activities of Daily Living Inventory modified for
      severe dementia (ADCS-ADL(19)), Functional Assessment Staging, and G2 scale. The
      present study reports a single-item analysis of the ADL scales from the two
      trials and shows that patients treated with memantine demonstrated a numerical
      advantage over placebo on all items assessed. These results help to translate the
      positive effects of memantine into specific aspects of functional ability,
      information that is relevant to AD patients and their families as well as to
      researchers interested in the assessment of functional ability in AD clinical
      trials.

PMID- 15256836
TI  - Banking of non-viable skin allografts using high concentrations of glycerol or
      propylene glycol.
AB  - The aims of this study were to investigate the kinetics of the current glycerol
      banking method for the preservation of non-viable skin allografts; to improve it
      with respect to efficiency and microbial safety; and to investigate the
      possibility of using propylene glycol in place of glycerol to provide a more
      rapid process. Skin grafts were preserved in 98% v/v glycerol (GLY) according to
      the method used in the Sheffield Skin Bank. During the addition and removal
      processes, the amounts of GLY and water in the skin were determined using the
      Karl Fischer method and HPLC respectively. Propylene glycol (PG) was investigated
      as an alternative to glycerol with the object of shortening the process. To avoid
      the need for prolonged storage in glycerol to disinfect the tissue, and to
      improve the effectiveness of disinfection, exposure to peracetic acid (PAA) was
      included and its influence on the kinetics of the preservation process was
      evaluated. The histological and ultrastructural appearances of skin that had been
      banked by these methods was also investigated. It was found that the permeation
      of GLY in skin probably involves two processes: diffusion and binding; the rate
      of transport was attenuated as the GLY concentration in the skin increased. The
      current incubation time could be shortened, but an inconveniently prolonged
      washout process was required. The substitution of PG for GLY accelerated the
      whole process, particularly the removal process, making the method more
      convenient for the emergency use of skin grafts in the clinic. The penetration of
      PG also involved diffusion and binding, but there was no attenuation of transport
      as the concentration increased. The addition of PAA sterilisation did not alter
      the transport of GLY or PG. Structural integrity was also maintained with the new
      banking treatments. An improved banking method can now be proposed; it can be
      completed in only one working day and the risk of disease transmission is
      reduced.

PMID- 15256837
TI  - Application of a high-level peracetic acid disinfection protocol to re-process
      antibiotic disinfected skin allografts.
AB  - Skin allografts, derived from cadaveric donors, are widely used for the treatment
      of burns and ulcers. Prior to use in clinical situations, these allografts are
      disinfected using a cocktail of antibiotics and then cryopreserved.
      Unfortunately, this antibiotic disinfection procedure fails to decontaminate a
      significant proportion and these contaminated grafts can not be used clinically.
      We have investigated whether it is possible to apply a second, more potent
      disinfection procedure to these contaminated grafts and effectively to re-process
      them for clinical use. Cadaveric skin grafts, treated with antibiotics and
      cryopreserved, were thawed and a peracetic acid (PAA) disinfection protocol
      applied. The grafts were then preserved in a high concentration of glycerol or
      propylene glycol, and properties thought to be essential for successful clinical
      performance assessed. The cytotoxicity of the grafts was assessed using both
      extract and contact assays; damage to the skin collagen was assessed using a
      collagenase susceptibility assay and the capacity of the grafts to elicit an
      inflammatory response in vitro was assessed by quantifying the production of the
      pro-inflammatory cytokine TNF-alpha by human peripheral blood mononuclear
      phagocytes. PAA disinfection, in conjunction with either glycerol or propylene
      glycol preservation, did not render the grafts cytotoxic, pro-inflammatory, or
      increase their susceptibility to collagenase digestion. The rates of penetration
      of glycerol and propylene glycol into the re-processed skin were comparable to
      those of fresh skin. This study has demonstrated that PAA disinfection combined
      with immersion in high concentrations of either glycerol or propylene glycol was
      an effective method for re-processing contaminated skin allografts, and may
      justify their clinical use.

PMID- 15256838
TI  - The measurement of water activity in allogeneic skin grafts preserved using high
      concentration glycerol or propylene glycol.
AB  - In the presence of free water, many degradation reactions can occur within stored
      tissues including enzymatic digestion, oxidation (peroxidation) and hydrolytic
      reactions, as well as the detrimental effects of microbial growth, therefore most
      long-term banking techniques are designed to avoid free water. One method
      currently used for banking of skin grafts is the use of high concentration (85%)
      glycerol as a preservative. In this case, the glycerol was assumed to dehydrate
      the skin by osmosis and diffusion out of the cells and skin matrix respectively.
      We have recently shown that this assumption is incorrect and the converse occurs,
      i.e. glycerol enters the skin and sequesters the water. It was therefore
      essential to determine whether enough water had been immobilised to prevent
      degradation of the tissue. Using an instrument (Pawkit) designed to measure water
      activity (aw) it was shown that a stepwise reduction in aw was achieved when the
      skin was immersed in 50 and 85% glycerol or propylene glycol, respectively. At
      the end of the glycerolisation process, the final aw was shown to be circa 0.3.
      An aw of 0.3 is known to minimise lipid peroxidation and reduce other degradation
      reaction rates to very low levels. It was concluded that the current
      glycerolisation protocol results in effective sequestration of water avoiding
      degradation of the skin during storage. The method presented should be used as a
      quality control step to confirm adequacy of preservation for each batch of
      glycerolised skin.

PMID- 15256839
TI  - The influence of different preservation and sterilisation steps on the
      histological properties of amnion allografts--light and scanning electron
      microscopic studies.
AB  - Despite thorough donor screening and preparation under aseptic conditions,
      conventional methods of preservation do not exclude the probability of a
      contamination with pathogenic germs. The purpose of this study was to investigate
      the changes of histological parameters of amnion transplants (ATs) through
      different methods of sterilisation and preservation. Therefore 10 different
      procedures for sterilisation and preservation of ATs were described. Specimens of
      each group were studied using different histological procedures such as light
      microscopy and scanning electron microscopy. General staining (Haematoxylin-eosin
      stain, periodic-acid-Schiff, Domack) and immunohistochemical methods have been
      applied in order to gain additional information concerning the structure of the
      amniotic epithelium and the basement membrane but also the distribution of
      collagens and intermediate filaments. Furthermore, the measurement of the ATs
      thickness was included in order to study the influence of the manufacturing
      procedures to this property. As a result we found that the histological
      appearance of the ATs is closely related to the applied sterilisation and
      preservation procedures. Although the basement membrane remained intact,
      especially the amniotic epithelium was partially destroyed by irradiation
      sterilisation. Further, the dissolution of the connective tissue layers into
      single fibre bundles was clearly visible. Procedures with and without peracetic
      acid sterilisation (PAA) preserved the tissue structure. Our results showed a
      significant variation in the tissue's thickness after different preservation
      procedures. Air- and freeze-dried ATs were found to be the thinnest tissues
      varying from 20 to 30 microm, the thickest ATs preserved in glycerol varied from
      45 to 50 microm. Because ATs showed a preserved tissue structure after PAA
      sterilisation it can be recommended as an alternative for methods previously
      described in literature. Depending on the specific use of the AT one may choose
      from thinner or thicker allografts.

PMID- 15256841
TI  - Editorial.

PMID- 15256840
TI  - Application of sterilised human amnion for reconstruction of the ocular surface.
AB  - BACKGROUND: Despite improved surgical techniques and the use of new medication,
      healing of corneal and conjunctival defects cannot always be achieved. In this
      connection the clinical use of human amnion, produced by different techniques,
      has represented a successful alternative for the past ten years. The purpose of
      the present investigation was the development of a clinically secure,
      therapeutically efficient, and easy-to-handle (transport, storage, application)
      allogenic amnion transplant. PATIENTS AND METHODS: A new method for an amnion
      preparation, which contains a sterilisation process in peracetic acid and a
      drying process in a laminar flow cabinet, was developed as an alternative to
      previous techniques described in the literature. Amnion transplantation was used
      to treat 41 patients, 36 of them with corneal ulcer. Further indications for
      amnion transplantation were symblepharon, descemetocele, as well as dehiscence of
      conjunctiva after cerclage. RESULTS: Seventy-three percent of cases showed
      postoperative improvement evidenced by constant vision, while 15 percent showed
      decreased vision. CONCLUSIONS: The study confirms the observations of previous
      investigators who consider amnion transplantation an efficient therapeutic method
      for a multitude of eye diseases. The new method described in this report,
      guarantees patients' safety by using a validated new sterilisation process
      against infections that can be transmitted by human tissue. At present this
      method constitutes the only process available in Germany, and is approved by the
      Federal Institute for Drugs and Medical Products (BfArM) for the manufacture of
      human amnion transplants as a finished medical product.

PMID- 15256842
TI  - The International Atomic Energy Agency (IAEA) Programme in Radiation and Tissue
      Banking: Past, Present and Future.
AB  - The International Atomic Energy Agency has developed a programme of tissue
      banking in more than 30 countries, based on the use of radiation for the
      sterilization of tissues. The value of the tissue grafts produced to the
      developing countries is not less than 62.6 million US dollars at the mean price
      of grafts in Europe and the U.S.A. To support this programme a training
      curriculum was developed which can now be delivered by internet in several
      languages, from the Universities of Singapore and Buenos Aires. Partnerships have
      been developed with major organizations which will extend this programme into
      2005-2006.

PMID- 15256843
TI  - IAEA/NUS Distance Learning Diploma Training Course for Tissue Bank Operators -
      Past, Present and Future.
AB  - National University Hospital (NUH) Tissue Bank as the Regional Training Centre
      for Asia Pacific Region provided National University of Singapore (NUS) Diploma
      Course in Tissue Banking - a long distance diploma course since 1997. To date,
      five batches have participated - 94 tissue bank operators. Sixty-three tissue
      bank operators have convocated with NUS Diploma in Tissue Banking.From Regional
      Co-operative Agreement (RCA) Project, RAS 7/008 technology transfer was effected
      to Latin America and to Africa.A Memorandum of Understanding has been signed
      between International Atomic Energy Agency (IAEA) and NUS in July 2002 making
      Singapore the International Training Centre. An Internet NUS Diploma Course in
      Tissue Banking has been developed by IAEA and NUS. The first on-line diploma
      course will be launched in 2003.

PMID- 15256844
TI  - A comparative evaluation of culture conditions for short-term maintenance (<24
      hr) of human islets isolated using the Edmonton protocol.
AB  - Once human islets are isolated, they are typically transplanted into type 1
      diabetic recipients within 2 h of isolation. This time restriction makes it
      difficult for patients to travel from distant locations to receive an islet
      transplant and it also makes it difficult to complete pre-release quality control
      assessments (i.e., endotoxin and gram stain) before the expiration of the islet
      product. Therefore, there were two goals for this study. The first was to measure
      the stability of islets after a 24 h culture period using CMRL media 1066 (CMRL)
      supplemented with either fetal bovine serum (FBS); albumin or insulin transferrin
      and selenium (ITS). The second was to determine the impact of cell concentration
      and media depth on islet stability. The results of the study indicated that
      culture recoveries at 37 degrees C with CMRL + ITS (also known as Memphis media)
      were higher (64.1 +/- 8.3%) than with CMRL supplemented with FBS (38.7 +/- 9.7%)
      or albumin (47.6 +/- 8.2%) and that post-culture islet viabilities, post-culture
      purities and stimulation indexes (SIs) were comparable. In the second series of
      experiments, the results showed that islets recoveries and SIs in cultures with
      low islet concentrations (300 IE/ml) were significantly better than cultures at
      high islet concentrations (1500 IE/ml). Additionally, at a shallow media depth
      (1.4 vs. 7 mm of media) the SI of the islets improved, and this effect was
      independent of the additive (i.e., FBS, albumin and ITS).

PMID- 15256845
TI  - Properties of Air Dried Radiation Processed Amniotic Membranes under Different
      Storage Conditions.
AB  - Amniotic membranes collected from the placentae of screened donors were
      processed, air dried and sterilized by gamma irradiation at 25 kGy. Effect of
      storage under different temperature and humidity conditions (10 degrees C, RH 80
      90%; 10 degrees C, RH 40-50%; 40 degrees C, RH 50-60% and 40 degrees C, RH 10
      20%) on the properties of the membrane were examined. Infrared (IR) spectral
      scanning was carried out to examine degradation or change if any in the tissue
      under different storage conditions. The degradation of amnion on irradiation with
      gamma rays or during storage after irradiation would tend to produce the relative
      variation in IR absorption troughs. This kind of addendum was absent in all the
      samples indicating no qualitative change in the material property of amnion.
      Water absorption and water vapour transmission rate (WVTR) of the membrane
      remained unchanged even after 6 months. No effect on the microbial permeability
      of membrane was observed during storage. The amniotic membranes were found to be
      impermeable to different strains of bacteria - Bacillus, Escherichia coli,
      Pseudomonas, Citrobacter, Flavimonas and Staphylococcus. The results indicate
      that amniotic membranes processed by air-drying are stable and can be stored
      under different environmental conditions without compromise to their clinical
      performance.

PMID- 15256846
TI  - Clinical evaluation of irradiated, freeze-dried dura mater allograft as a
      collagen-based barrier in periodontal osseous defects.
AB  - The objective of this study was to clinically evaluate freeze-dried dura mater
      allograft (FDDMA) provided by the Tata Memorial Hospital Tissue Bank, in various
      periodontal osseous defects and to observe any unwanted healing pattern or
      adverse reaction.Eleven systemically healthy patients with one
      infrabony/furcation defect and at least 6 mm or more loss of attachment at
      selected sites, were scheduled for surgery. At base-line, patients had a good
      maintenance regime, minimal gingival inflammation and mobility not more than 1 mm
      in the buccolingual plane (grade 2). The measurements taken were probing pocket
      depth, clinical attachment level, intrasurgical level of bone and radiographic
      level of bone. Instead of surgical re-entry, transgingival probing was performed
      after 12 months of surgery. After debridement the defects were filled with
      demineralised freeze-dried bone allograft and covered with FDDMA barrier. The
      results after 12 months were satisfactory (mean gain of attachment 4.33 mm and
      mean defect fill 3.91 mm). No adverse reaction, infection or delayed wound
      healing was noted throughout the study.

PMID- 15256847
TI  - Reconstructing tumour defects: lyophilised, irradiated bone allografts.
AB  - Tumour excision leaves behind large defects. Allografts provide an excellent
      alternative to autografts without donor site morbidity and are especially useful
      in large defects or in children where the quantity of available autograft is
      limited. In this paper we discuss our experience with indigenously procured and
      processed lyophilised, irradiated bone allografts. Bone allografts were used in
      41 patients. They were used morsellised and used in 32 cases. Of these, 25 cases
      were available for follow-up. These included 21 patients in whom the allograft
      was used in contained cavities. Complete incorporation of the graft was seen
      between 6 and 9 months in all these 21 patients. In 4 patients the allograft was
      layered onto autograft. In only one of these the allograft incorporated with the
      host bone. Struts were used in 9 cases (3 cases complete intercalary segmental
      defect, 3 cases of hemicortical defects, 2 cases of allograft-prosthesis
      composite around the hip, in 1 case an iliac-crest block was used to stop
      bleeding from an anterior sacral defect). Of these, 2 full segment struts showed
      no incorporation. Both these patients were on chemotherapy and radiotherapy.
      There was no follow-up in sacral defect case. All the other struts incorporated
      with the host bone within 6-9 months.In 5 cases there was sterile postoperative
      drainage. All these cases went on to uneventful. Deep infection was observed in 4
      patients (10%). In one, the graft was removed, another settled uneventfully with
      subsequent incorporation of graft, and two have a persisting sinus but good
      incorporation.To restore part of the strength of the struts it was necessary to
      hydrate them for 30 min prior to use. Autogenous marrow or autograft was used to
      provide osteoinductive properties.Conclusion. In selected cases the lyophilised,
      irradiated bone allografts proved to be very useful in reconstruction of large
      tumour defects.

PMID- 15256848
TI  - The use of Irradiated Allografts in Posterior Spinal Fusion for Healed Tubercular
      Kyphosis in Children.
AB  - Post-tubercular spinal kyphosis in children is not only cosmetically unacceptable
      but functionally disabling as well, as with the progression of the deformity
      there is a very significant risk of late onset paraplegia. We present our
      preliminary results in a prospective study of 12 cases of healed post-tubercular
      kyphosis in children treated with isolated posterior spinal fusion using
      irradiated allografts and autogenous cancellous grafts.The study included 12
      patients of healed post-tubercular kyphosis documented by clinical, radiological
      and haematological criteria, with >2 spine at risk signs radiologically. The mean
      age was 7 years. In situ posterior spinal fusion with irradiated allografts and
      autogenous cancellous bone graft without any instrumentation was done for all the
      patients. The total follow-up is 5 years (mean 2.8 years).Eight patients (66%)
      showed a correction of the kyphosis, 3 patients (25%) were static and only 1
      patient showed worsening of the deformity. Eleven patients had sound fusion and 1
      patient had good fusion but a pseudoarthrosis at the lower vertebral level.Good
      posterior fusion was achieved because of the judicious use of morcellised,
      irradiated cancellous allografts with autogenous cancellous grafts. The proposed
      mechanism of correction is selective anterior column growth vis-a-vis posterior
      fused mass leading to gradual self-correction and remodelling.Conclusion. In situ
      posterior spinal fusion with irradiated allografts is a simple, safe, easily
      reproducible, less morbid surgical procedure with good results which may alter
      the long term disability of the patients.

PMID- 15256849
TI  - The use of irradiated allografts in reconstruction of tumor defects - the tata
      memorial hospital experience.
AB  - A Tissue Bank is a valuable adjunct to tumour management. In bone tumours, the
      defects produced by ablative surgery can be reconstructed using banked tissue,
      thereby obviating the donor site morbidity associated with autografts. Allografts
      are especially useful in large defects or in children where the quantity of
      available autograft is limited. The use of bone allografts in India has been
      limited by the availability of good quality, affordable grafts. In this article
      we share our experience with the use of indigenously produced allografts in limb
      salvage, as bone graft expanders and as struts. Lyophilised, irradiated bone
      allografts were morcellised and used in 32 patients. In 21 of these patients the
      allograft was used in contained cavities. Complete incorporation of the graft was
      seen between 6-9 months in all the 25 cases available for follow-up. In 4
      patients the allograft was layered onto autograft. The allograft incorporated
      with the host bone in only one of these patients.Struts were used in 9 cases (3
      cases complete intercalary segmental defect, 3 cases of hemicortical defects, 2
      cases of allograft-prosthesis composite around the hip, 1 case an iliac-crest
      block was used to stop bleeding from an anterior sacral defect). Of these, no
      incorporation of the full segment struts was observed in 2 patients who were on
      chemotherapy and radiotherapy. The sacral defect case was lost to follow-up. All
      the other struts incorporated with the host bone within 6-9 months. In 5 cases
      there was sterile postoperative drainage. Overall infection was observed in 4
      patients (10%). In one the graft was removed, another settled uneventfully with
      subsequent incorporation of graft, and two have a persisting sinus but good
      incorporation. Since radiation and lyophilisation are known to affect the
      material properties of bone, the grafts were rehydrated in saline for 30 minutes
      prior to transplantation. Autogenous marrow or autograft was used to provide
      osteoinductive properties. In selected cases the lyophilised, irradiated bone
      allografts proved to be clinically useful in the reconstruction of large tumour
      defects.

PMID- 15256850
TI  - Evaluation of Freeze-Dried Dura Mater Allograft as a Collagen Based Barrier (an
      experimental animal study).
AB  - Freeze-dried dura mater allograft (FDDMA) was evaluated as a cost-effective
      collagenous barrier using an experimental animal model to determine its
      biocompatibility and 'cell-occlusivity' potential. The FDDMA was processed at the
      Civil Hospital Ahmedabad, in accordance with the guidelines provided by the South
      Eastern Organ Procurement Foundation, U.S.A. Fifteen Charles Foster rats were
      selected for a study period of 9 weeks. The 1st set graft procedure was performed
      in an abdominal pouch and after 1 week bilateral mandibular defects were created.
      One defect was covered by the FDDMA barrier (2nd set graft procedure) and the
      other defect served as the control. The post operative autopsy and morphological
      and histological assessments were carried out at 2 and 4 weeks for the 1st set
      graft, and 3, 6 and 9 weeks for the 2nd set graft procedure. There was acceptance
      of the 2nd set graft in a pre-exposed animal and no significant inflammatory
      response. The processed FDDMA demonstrated optimal 'cell-occlusivity' potential
      for guided bone regeneration to take place in Charles Foster rats.

PMID- 15256851
TI  - Use of banked tissue in plastic surgery.
AB  - The availability of safe and reliable, banked tissues in India has enabled the
      use of human bone allografts as a viable alternative to autografts in
      reconstructive surgery. Lyophilised, irradiated bone grafts were used in 2 cases
      of rhinoplasty, a case of hemifacial atrophy, and as a chin implant.In the
      patient with revision rhinoplasty the rib graft was resorbed. The patient with
      hemifacial atrophy developed seroma and infection in the zygomatic and
      infraorbital area and the rib graft had to be removed. The graft from the same
      rib that was placed over the mandible was retained well and incorporated
      completely. The iliac crest cortico-cancellous grafts did well in the second case
      of augmentation rhinoplasty and in the augmentation of chin.The primary objective
      of reconstructive surgery in the treatment of burns, non-healing wounds and
      pressure sores is to remove the dead tissue and restore the continuity of the
      skin without delay. Lyophilised, irradiated, human amnion is a temporary
      biological dressing conveniently available off-the-shelf. It was used in twenty
      four patients with burns, eight patients with bedsores and six patients with non
      healing ulcers mainly on the foot. The total surface areas of burns sustained
      were from 2% to 40%. The burns ranged from second degree to deep third degree
      burns. Amnion was not used in patients with infected third degree burns.The
      amnion provided good biological cover in all the patients. It was easy to handle
      and apply, and provided pain relief. The duration of healing varied depending on
      the extent and depth of the wound and the amount of exudate. The superficial
      bedsores healed with a single application of amnion. Reduced exudate, healthy
      granulation tissue and enhanced epithelisation were observed following
      application of amnion.

PMID- 15256852
TI  - Use of irradiated amnion as a biological dressing in the treatment of radiation
      induced ulcers.
AB  - The management of moist skin desquamation (ulceration) following radiation
      therapy has been a concern since the inception of this therapy. The treatment of
      skin reactions focuses on promoting healing, improving patient comfort preventing
      infection and decreasing trauma to the area. Various dressings like topical
      preparations, hydrocolloid and gentian violet 1 % dressing have been used for its
      treatment. We present our experience with the use of amnion as a biological
      dressing in patients with radiation induced ulceration following pelvic radiation
      using megavoltage beam. The preliminary experience with treatment in 14 patients
      proved to be cost effective due to a shorter duration of ulcer healing (median of
      7 days), fewer dressing changes (median of 4 dressings) and diminished use of
      analgesics.

PMID- 15256853
TI  - Tissue banking in australia.
AB  - The legal structure for the regulation of tissue banking has existed for many
      years. In Australia, the donation of human tissue is regulated by legislation in
      each of the eight States and Territories. These substantially uniform Acts were
      passed in the late 1970's and early 1980's, based on model legislation and
      underpinned by the concept of consensual giving. However, it was not until the
      early 1990's that tissue banking came under the notice of regulatory authorities.
      Since then the Australian Government has moved quickly to oversee the tissue
      banking sector in Australia. Banked human tissue has been deemed to be a
      therapeutic good under the Therapeutic Goods Act 1989, and tissue banks are
      required to be licensed by the Therapeutic Goods Administration and are audited
      for compliance with the Code of Good Manufacturing Practice- Human Blood and
      Tissues. In addition, tissue banks must comply with a myriad of other standards,
      guidelines and recommendations.

PMID- 15256854
TI  - The colombian experience in tissue banking: the bone and tissue bank of the
      cosmos and damian foundation, bogota.

PMID- 15256855
TI  - The tissue bank at the national nuclear research institute in Mexico.
AB  - The Instituto Nacional de Investigaciones Nucleares (ININ, The National Nuclear
      Research Institute) received during 1997-1998 strong support of the International
      Atomic Energy Agency (IAEA), to establish the first and only one tissue bank (BTR
      ININ tissue bank) in Mexico that uses ionising radiation as sterilising agent. In
      that time, the BTR staff was trained in different tissue banks in several
      countries. Basic equipment for tissue processing donated by the IAEA was received
      in 1998. In July, 1999 the Mexican Health Secretariat gave the Sanitary License
      No. 1062000001 to the BTR to operate as an official organ and tissue bank. In
      August, 2001 the ININ and the Hospital Materno Infantil (HMI-ISSEMYM) signed an
      agreement to collaborate in amnion processing. The hospital is responsible for
      donor selection, serology tests, tissue procurement and washing, since this
      hospital is the BTR amnion supplier. The tissues are collected by ININ weekly
      with complete documentation. The BTR is responsible for processing: cleaning, air
      drying, packaging, labelling, microbiological control and sterilisation by gamma
      irradiation. The sterilised tissue is kept under quarantine for 6 months to
      obtain the results of the donor second serology test. From March to June, 2002
      the BTR has processed 347.86 units (50 cm(2) each), is say, 17,393 cm(2). In
      addition, the pig skin xenograft process has been implemented and a protocol for
      clinical applications of it is running at the Hospital Central Sur de Alta
      Especialidad (PEMEX). Also the ININ tissue bank present status and perspectives
      are described.

PMID- 15256856
TI  - Initiation of bone and amnion banking in Turkey.
AB  - There is a growing demand in Turkey for human tissue to use in surgery and wound
      healing. However, our country does not have facilities for local production of
      tissue grafts and generally depends on imported products. Under a multi-year
      project initiated in 1997, the International Atomic Energy Agency has provided
      main equipment for tissue processing and experts on Tissue Banking as well as
      training on tissue processing methods.In this presentation, information on
      various stages of the project implementation is given. Details of lay out for the
      process laboratories and equipment are given. Donor selection and testing
      criteria, processing procedures for bone and amnion, setting up product design,
      implementation of quality system and radiation sterilisation are described
      briefly. Quality procedures included preparation of quality manual, record forms,
      document control, non-conformance and corrective actions, training records,
      equipment maintenance and calibration are all in line with GMP/GLP Standards.
      Clinical applications of tissue grafts and medico-legal position of organ and
      tissue donation in Turkey are also discussed briefly.

PMID- 15256857
TI  - Progress of National Multi-tissue Bank in Uruguay in the International Atomic
      Energy Agency (IAEA) Tissue Banking Programme.
AB  - The transplant law of 1971 based on informed consent, allows people to register
      their willingness to be a donor upon death. Since 1978 the governmental
      Institution, the National Bank of Organs and Tissues (BNOT), have been regulated
      the organ and tissue donation. Important progress was implemented in the BNOT and
      specially in the National Multi-tissue Bank (NMTB). Since 2001 with the
      participation in the IAEA Tissue Banking Programme, Quality System Management has
      been implemented in the NMTB. New bio-production for radiosterilized tissues for
      the first time and improved procedures were carried out. As a result an increased
      production of high-quality tissues was obtained and distributed for clinical use.

PMID- 15256858
TI  - Slovakia: five years experience of multitissue bank with the production of
      allografts and cultured living cells.

PMID- 15256859
TI  - Indonesia: statistical sampling technique in validation of radiation
      sterilisation dose of biological tissue.
AB  - The aim of the work is to find the best solution for statistical sampling
      technique in validation of radiation sterilization dose (RSD) for biological
      tissues, according to ISO standard. As a model for sampling are biological
      tissues retrieved from one cadaver donor which consist of frozen bone grafts (18
      packets), lyophilized allografts (68 packets) and demineralized bone powder
      grafts (40 packets). The size and type of products vary from long bones,
      cancellous chips to bone powders, tendons and facia lata, that make the number of
      bioburden per product could not be treated equally. Frozen samples could not be
      considered as the same production batch with lyophilized samples, because of
      different processing and irradiation temperature. The minimum number of uniformed
      samples needed for validation per production batch size, according to ISO 13409,
      is from 20 to 79 and 20 of them will be used for the test sample size, i.e. 10
      for bio-burden determination and the remaining 10 for verification dose. Based on
      the number of uniformed grafts, statistical sampling can be carried out on
      lyophilized and demineralized bone grafts, but not on frozen bone grafts.
      Bioburden determinations were carried out and validated according to ISO 11737-1.
      Results of average bioburden determination (cfu/per packet), using sample item
      portion (SIP) = 1, are 5 cfu/packet for lyophilized bone grafts and 4 cfu/packet
      for demineralized bone powder grafts. Verification doses obtained were 2.40 kGy
      for lyophilized grafts and 2.24 kGy for demineralized bone powder grafts. The
      results of verification dose were accepted and the RSD of 25 kGy is substantiated
      It can be concluded that a statistical sampling technique can be applied if all
      the grafts produced in the same process such as lyophilized, demineralized as
      well as frozen are assumed to be in one production batch regardless of sample
      uniformity such as size, type and weight; for this ISO 13409 can be applied for
      the validation of RSD.

PMID- 15256860
TI  - Setting up a Tissue Bank in India: The Tata Memorial Hospital Experience.
AB  - In India, the procurement of tissues for transplantation is governed by the
      Transplantation of Human Organs Act, 1994. However, although this law exists, it
      is primarily applied to organ transplantation and rules and regulations that are
      specific to tissue banking have yet to be developed.The Tata Memorial Hospital
      (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy
      Agency (IAEA) programme to promote the use of ionising radiation for the
      sterilisation of biological tissues. It represents the Government of India within
      this project and was the first such facility in the country. It is registered
      with the Health Services Maharashtra State and provides lyophilised amnion, dura
      mater, skin and bone that have been terminally sterilised with exposure to 25 kGy
      of gamma radiation from a Cobalt 60 source. These are obtained either from
      cadavers or live donors.To date the TMH Tissue Bank has provided 6328 allografts
      for use as biological dressings or in various reconstructive procedures.The TMH
      Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL),
      Jodhpur. At present these are the only two Banks in the country using radiation
      for terminal sterilisation of banked tissues.The availability of safe, clinically
      useful and cost effective grafts have resulted in changes in surgical treatment
      with a concomitant increase in demand for grafts and an interest in developing
      more tissue banks. The availability of donor tissue however, continues to be a
      major limitation.

PMID- 15256862
TI  - Report from the First Annual Meeting of the Latin America Tissue Banks on
      Legislation and Policies adopted by Tissue Banks in the Region.

PMID- 15256861
TI  - Tissue banking in India: gamma-irradiated allografts.
AB  - In India, the procurement of tissues for transplantation is governed by the
      Transplantation of Human Organs Act, 1994. Although this law exists, it is
      primarily applied to organ transplantation and rules and regulations that are
      specific to tissue banking which have yet to be developed. The Tata Memorial
      Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic
      Energy Agency (IAEA) programme to promote the use of ionising radiation for the
      sterilisation of biological tissues. It represents the Government of India within
      this project and was the first facility in the country to use radiation for the
      sterilisation of allografts. It is registered with the Health Services
      Maharashtra State and provides freeze-dried, gamma irradiated amnion, dura mater,
      skin and bone. The tissues are obtained either from cadavers or live donors. To
      date the TMH Tissue Bank has provided 6328 allografts which have found use as
      biological dressings and in various reconstructive procedures. The TMH Tissue
      Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur.
      At present these are the only two Banks in the country using radiation for the
      terminal sterilisation of preserved tissues. The availability of safe, clinically
      useful and cost effective grafts has stimulated innovative approaches to surgery.
      There is an increased demand for banked tissues and a heightened interest in the
      development of tissue banks. Inadequate infrastructure for donor referral
      programmes and the lack of support for tissue transplant co-ordinators however,
      continue to limit the availability of donor tissue.

PMID- 15256863
TI  - Status of Bone Allografting in Japan - Nation-Wide Survey of Bone Grafting
      Performed from 1995 through 1999.
AB  - We report the status of bone allografting in Japan on the basis of the
      information obtained through questionnaires performed by the Japanese Orthopaedic
      Association (JOA). JOA performed a nation-wide survey in 2000, in order to
      clarify the current status of musculoskeletal tissue grafting in the orthopaedic
      practices in Japan. Conducted period was for 5 years from 1995 to 1999. As the
      results of this survey, it had been clarified that 92,984 bone graftings, which
      included autografts, allografts and synthetic bone substitutes, were performed
      during conducted 5 years. While the allografts were used only in 3,212 cases
      (3%), autograftings were performed in 64,193 cases (69%), synthetic bone
      substitutes were used in 25,576 cases (28%) in this series. The proportion of the
      number of operations for use bone substitutes increased every year, whereas that
      autografting decreased. The proportion of the number of allografting remained
      almost unaltered. Of the 706 institutions which answered to have experiences of
      tissue grafting, only 193 (27%) performed allograft.Since Kitasato University
      Hospital Bone Bank was developed in 1971, we have applied to clinical while doing
      basic research for preserved bone allograft. When extensive bone graft is
      required, allograft is very useful. In Japan, however, allograft is not performed
      widely. The foundation of regional bone banks is expected to resolve this
      problem. Since excision of bone preparations from cadaver donors is not common,
      bone allografts are not supplied sufficiently at present. It is needed to develop
      a network connecting bone banks in Japan. The enlightenment activities to the
      ordinary people and medical institutions will also be required.

PMID- 15256864
TI  - Cryopreservation of hepatocytes: a review of current methods for banking.
AB  - Cryopreservation, the freezing of hepatocytes in liquid nitrogen for storage, has
      been investigated for many years, as a method of long-term storage for
      hepatocytes. Unfortunately an agreed acceptable protocol has been elusive, in
      part due to the susceptibility of hepatocytes to the freeze thaw process
      involved. A method for long-term storage (months, possibly years) of human
      hepatocytes, in particular, is desirable for the development of a clinically
      applicable bioartificial liver, hepatocyte transplantation and for
      pharmacotoxicological research. The sources of human liver tissue from which
      hepatocytes can be derived are limited. Many groups have modified and improved
      the process of cryopreservation and many new techniques have been published,
      including the incorporation of such cryopreserved cells in clinically based
      studies. Further evaluation is still required to develop a universally acceptable
      protocol. This article reviews the difficulties involved in cryopreserving
      hepatocytes for banking and examines recent technical advances within this field.

PMID- 15256865
TI  - Ability of a bovine bone graft, alone or enriched with PDGF-BB or rhBMP-2, to
      promote human periodontal ligament (PDL) cells proliferation. A preliminary
      study.
AB  - One of the most important goals of the periodontal therapy procedures is to
      stimulate the formation of new bone into osseous defects resulted from
      periodontal disease. A wide range of grafting materials is used to achieve this
      aim. Recently, the Human Tissue Bank of the National Center for Scientific
      Research 'Demokritos' in Athens (Greece) has prepared, in a preliminary study, a
      cancellous bovine-derived bone matrix (BBM). The purpose of the present work was
      to investigate the role of this bovine bone material in the periodontal
      regeneration, by studying the rate of human periodontal ligament (PDL) cells
      proliferation in the presence of this matrix alone, or after the addition of the
      growth factors, platelet-derived growth factor-BB (PDGF-BB) or recombinant human
      bone morphogenetic protein-2 (rhBMP-2).Bovine bone graft was prepared using the
      'know how' acquired by the 30 years continuous preparation and delivery of
      lyophilized human bone grafts by the 'Demokritos' Bank.PDL cells cultures were
      derived from the mid root of two maxillary premolars. The teeth were caries-free
      and were extracted for orthodontic reasons from 1 adult female patient. Cells
      were grown in 24-well dishes in the presence of 20 mg BBM. On day 2 of
      quiescence, new medium was added with 10 ng/ml of PDGF-BB or 50 ng/ml of rhBMP-2.
      To determine the effects of the test agents on cell proliferation, DNA synthesis
      was estimated by measuring [(3)H] thymidine incorporation. After 48 h of
      incubation the cells were processed to subject to scintillation counting. Counts
      per minute (cpm/well) were determined for each sample.The results revealed that
      this BBM has the ability to maintain PDL cells proliferation and could be used as
      an alternative graft material. PDGF-BB when added improved the cell proliferative
      response resulting in a more active BBM, while the presence of rhBMP-2 did not
      support cell mitosis.

PMID- 15256866
TI  - IgE-Independent Activation of Human Mast Cells Indicates their Role in the Late
      Phase Reaction of Allergic Inflammation.
AB  - Mast cells are tissue dwelling cells that have a clear-cut pathologic role in
      allergy. Besides that, they participate in several chronic inflammatory
      conditions, helminitic parasitosis, and in some solid tumor reactions, but also
      in physiological situations, such as wound healing and innate immunity. Mast
      cells produce and release various mediators after activation induced by either
      IgE-dependent or IgE-independent mechanisms. Although much information has been
      gathered on the immunological (IgE-dependent) mast cell activation both in vivo
      and in vitro, not much is known about the non-immunological (IgE-independent)
      activation particularly in human mast cells. Mast cell IgE-independent activation
      is mediated through Gi3alpha which has been identified in rat mast cells as the
      pertussis toxin (Ptx)-sensitive heterotrimeric G protein that interacts with
      cationic secretagogues inducing PLC-independent mast cell exocytosis. Mast cell
      IgE-independent activation in allergy most likely occurs when mast cells
      encounter eosinophils, the main inflammatory cells that persist throughout the
      late and chronic phases of the allergic reaction. This review summarizes the
      influence of eosinophils on mast cell activation demonstrating that IgE
      independent activation has a significant role in pathophysiological processes.

PMID- 15256867
TI  - Unrelated and related cord blood banking and hematopoietic graft engineering.
AB  - The first successful transplantation of umbilical-cord blood (CB) was performed
      in 1988 to treat a boy with Fanconi's anemia, using CB from his HLA full-matched
      sister. A few years later, CB transplantation (CBT) was also performed in an
      adult recipient, however major obstacles still prevent a wider application of CBT
      in this age group. The principle limiting-factor is the low numbers of nucleated
      (NC) and CD34+ cells available for transplantation compared to a typical bone
      marrow (BM)/peripheral blood (PB) allograft, resulting in a lower engraftment
      success as well as delayed hematopoietic recovery with its characteristic
      complications, including infections and transplant related mortality (TRM). Other
      problems include uncertainty regarding potency and efficacy of graft versus
      leukemia (GvL)/tumor effects in this kind of transplant, considering the reduced
      graft versus host disease (GvHD) manifestations and immunologic prematurity.
      These subjects are reviewed with orientation to technical methods directed to
      improve CB grafts and graft engineering.

PMID- 15256868
TI  - Composite grafts in the treatment of osteosarcoma of the proximal humerus.
AB  - Treatment of osteosarcoma (OSA) of the proximal humerus poses many difficulties
      and challenges to the treating team. Between 1993 and 2000, we treated 11
      patients (three women, eight men; age range, 17-74 years) suffering from OSA of
      the proximal humerus by 'composite': massive allografts and long humeral
      prosthesis. At presentation, 10 patients were at stage 2-B and one at stage 3-B
      of OSA. One patient presented with a pathologic fracture. All patients except
      patient No. 6, received preoperative chemotherapy followed by limb salvage
      surgery and postoperative chemotherapy.Surgical margins were graded as wide in
      all patients. Postoperative complications included non-union at the
      allograft/host junction (which united after auto grafting) and superficial wound
      infections that resolved after antibiotic therapy. All surgical procedures were
      performed by a team headed by an orthopedic oncologist and shoulder surgeon. At
      latest follow-up (December 2001) all patients, with the exception of one (who was
      at stage 3-B at presentation) were alive, and had good function of the upper
      limb. It is our opinion that the team approach comprising an orthopedic
      oncologist and shoulder surgeon greatly contributed to the good surgical outcome,
      and hence the good survival and functional results of the patients. Bone
      allograft offers a modular malleable durable solution to the resected bone
      segment.

PMID- 15256869
TI  - 30 years of bone banking at Turku bone bank.

PMID- 15256870
TI  - Charitable State-Controlled Foundation Human Tissue and Cell Research: Ethic and
      Legal Aspects in the Supply of Surgically Removed Human Tissue For Research in
      the Academic and Commercial Sector in Germany.
AB  - Tissue engineering using human cells and tissue has one of the greatest
      scientific and economical potential in the coming years. There are public
      concerns during the ongoing discussion about future trends in life sciences and
      if ethic boundaries might be respected sufficiently in the course of striving for
      industrial profit and scientific knowledge. Until now, the legal situation of
      using human tissue material for research is not clear. Accordingly, transparency
      of action and patients' information are a central component when handling patient
      material inside and outside of the patient-specific treatment. Whereas in the
      field of therapeutic use of tissue (e.g. transplantation) there is an emergency
      situation by the shortage of organs with the risk of the premature death of the
      potential recipient, this cannot be claimed for tissue donation for research. The
      basis of every surgical operation is the treatment contract, which places the
      doctor under obligation to the careful exercise of medical treatment containing
      the patient's informed consent. This contract only covers the treatment that is
      intended to cure the patient and the medical measures that are necessary
      therefor. The further scientific use of body-substances, which are discarded
      after an operation, are not included. Therefore a personal and independent
      written enlightenment of the patient and a declaration of informed consent is
      necessary. Examples of guidelines for tissue supply, Patients information and
      consent were worked out by theologists, lawyers, scientists and physicians
      reflecting their practical experience in transplant surgery and liver cell
      research. As a consequence to cover the ethical and legal aspect of tissue
      donation in Germany a charitable state-controlled foundation Human Tissue and
      Cell Research (HTCR) was introduced and established.

PMID- 15256871
TI  - Influence of pre-, intra- and post-operative parameters of donor liver on the
      outcome of isolated human hepatocytes.
AB  - The aim of the present study was to analyse, retrospectively on a large panel of
      patients (149), the influence of the donor liver characteristics on the outcome
      of human hepatocyte isolation obtained from resected liver biopsies from surgical
      waste after hepatectomy. Among the pre-operative parameters, the type of disease,
      age and sex of the patient, previous chemotherapy, alcohol or tobacco consumption
      did not affect the yield, viability, attachment rate and function of the isolated
      human hepatocytes. Pre-operative biological and anatomopathological data
      indicated that, while mild steatosis (</=10% steatotic hepatocytes) did also not
      affect the outcome of hepatocyte isolation, stronger steatosis (>10% steatotic
      hepatocytes) tended to decrease hepatocyte yield. Cholestasis, as assessed by
      gamma-glutamyl transferase serum values, significantly negatively correlated with
      the percentage of digested liver and the yield of viable cells. Intra-operative
      clamping time, that is, warm ischaemia, longer than 30 min was found to decrease
      both the percentage of digested liver and cell yield. Among the post-operative
      parameters, the percentage of digested liver decreased when biopsy weights were
      higher than 100 g, the use of glue tended to increase both the percentage of
      digested tissue and the yield of viable cells.In conclusion, human diseased
      livers appear to be a valuable source of isolated functional human hepatocytes.
      We recommend, for an optimal isolation, to use liver biopsies weighing less than
      100 g, to glue the section surfaces of the biopsies and to avoid the use of
      moderate steatotic livers (>10% steatotic hepatocytes) and cholestatic livers, as
      well as livers undergoing warm ischaemia or clamping during resection due to the
      decrease in cell yield.

PMID- 15256873
TI  - Effectiveness and Safety of the PEGT/PBT Copolymer Scaffold as Dermal Substitute
      in Scar Reconstruction Wounds (Feasibility Trial).
AB  - Skin defects left after excision of hypertrophic scars were treated with a dermal
      substitute and split-thickness skin grafts transplanted after vascularisation of
      the substitute. The used substitute was a synthetic porous scaffold made from the
      biodegradable copolymer polyethyleneglycol-terephtalate and polybuthylene
      terephtalate. The study was designed to assess the rate of granulation tissue
      formation, graft take, and after 3 and 12 months the quality of life (pain,
      comfort of treatment, cosmetic or functional nuisance), scar formation and wound
      contraction. In addition, scaffold biodegradation and scar tissue formation were
      evaluated histologically.Seven patients with different causes of burn injury were
      enrolled, of which 5 completed the study. In the first 4 patients the time
      between scaffold application and split-thickness skin overgrafting was in between
      17 and 24 days. The time point of overgrafting was significantly reduced to 10-12
      days by meshing of the dermal scaffold as evidenced in the last 3 patients.
      Histological evaluation at 3 months revealed normal generation of dermal tissue,
      however, the collagen bundles were parallel organized like in scar tissue. In the
      deeper layers of the neodermis, fragments of the dermal substitute were present,
      causing a mild inflammatory response. One year post-treatment, some fragments of
      the copolymer were still observed. The extent of wound contraction after
      successful overgrafting ranged from 30% to 57% after 1 year. All 5 patients
      showed an improvement in the total Vancouver Scar Score compared to the value
      before scar removal being similar to what can be expected when treated with split
      thickness skin grafts alone. No unanticipated adverse effects due to application
      of the substitute were observed.We conclude that although this synthetic dermal
      substitute can be safely used in humans, the presence of 3D dermal template in a
      full-thickness skin defect will not automatically improve the skin tissue
      regeneration process or inhibit wound contraction.

PMID- 15256872
TI  - Clinical efficacy and compatibility of allogeneic avital tissue transplants
      sterilized with a peracetic acid/ethanol mixture.
AB  - In the course of the past 20 years a quantity of approximately 60,000 allogeneic
      avital tissue grafts sterilized with the peracetic acid-ethanol method (PES) were
      transplanted successfully. Based on a retrospective report of clinical experience
      of the years 1997-2001 on the overall scope of tissue grafts manufactured by the
      Tissue Banks of the University Hospital Charite and the German Institute for Cell
      and Tissue Replacement, the clinical efficacy and side effects of 18.3%
      (3.087/16.823) of all transplants were studied. Cancellous (1.601/3.087) and
      cortical (291/3.087) bone transplants as well as amnion (1.027/3.087) constituted
      the greatest part. In 91% of the examined patients (2.369/2.592) tissue
      integration ratios ranging from good up to very well could be observed. The
      transplant function of defect replacement or of a spacer respectively could be
      obtained for all types of tissue. The clinical effect caused by the transplant
      resulted in more than 99% of the transplants in primary integration or in the
      desired aim of the therapy (defect replacement, stabilization in case of
      palliative operations, etc.). In less than 1% (9/2.592) of cases a secondary
      healing occurred for cancellous bone transplantations or, revisional operations
      became necessary. In all cases severe side effects, in particular transmission of
      infectious diseases or transplant rejections, were not observed.

PMID- 15256874
TI  - Bone grafts and bone morphogenetic proteins in spine fusion.
AB  - Spinal fusions are being performed for various pathologies of the spine.
      Stabilizing vertebral segments by eliminating motion across those segments
      becomes critical in dealing with pathologies of the spine that lead to
      instability. The use of autograft has been the gold standard for spine fusion.
      However, due to complications such as donor site morbidity, increased operating
      time, and limited supply, the use of allograft as a graft extender has become an
      acceptable practice especially in fusions spanning multiple segments. The
      discovery and isolation of novel proteins (i.e., bone morphogenetic proteins,
      BMPs), which initiate the molecular cascade of bone formation, have
      experimentally been shown in numerous animal studies to be as effective as
      autografts. Although the use of BMPs has exciting applications in spine surgery,
      long-term clinical studies must be evaluated for its efficacy in various
      applications in humans. The use of biomimetic materials such as hydroxyapatite
      (HA), or tricalcium phosphate (TCP) has also been examined in several animal
      models as bone graft substitutes or carriers. Although these materials have shown
      some promise in specific site applications, more work remains in elucidating an
      efficacious combination of these materials and BMPs that can be as effective as
      autografts. This review will present the status of bone grafts, bone
      morphogenetic proteins, gene therapy, and work that has been done to facilitate
      spinal fusion and simultaneously eliminate the need for bone graft.

PMID- 15256875
TI  - Articular cartilage reconstruction using xenogeneic epiphyses slices.
AB  - Reconstruction of articular cartilage defects using adult osteochondral
      allografts is an established clinical procedure, whose principal drawback is lack
      of lateral integration of the grafts to the surrounding tissue. Autologous
      chondrocytes transplantation is a sophisticated technique requiring cell culture
      and a staged operation. Its main draw back is the lack of mechanical strength
      early on. This study was conducted in order to evaluate the possibility of using
      embryonal epiphyses as a cartilage reconstruction tissue. A xenogeneic human to
      rabbit sub-acute osteochondral defect model was designed to evaluate the
      possibility of allogeneic implantation in humans. The following procedures were
      perfomed (n = 5): transplantation of 1. live epiphyses 2. live epiphyses with
      autogeneic periosteum 3. de-vitalized epiphyses and 4. devitalized epiphyses with
      autogeneic articular chondrocytes. A fifth control group did not receive any
      implant. Animals in groups 1 and 2 had a viable reconstruction of the articular
      surface with little evidence of rejection and without pannus formation. Animals
      in groups 3 and 4 became severely arthritic and the graft was resorbed. Nitric
      oxide synthase accumulation was reduced in group 1 and 2 as compared to groups 3,
      4, and 5, indicating a joint preserving function of the epiphyseal grafts.
      Epiphyseal grafts appear to be a feasible procedure for reconstruction of
      articular cartilage defects even in a xenogeneic model.

PMID- 15256876
TI  - Banking of osteochondral allografts. Part I. Viability assays adapted for
      osteochondrol and cartilage studies.
AB  - The aim of this study was to adapt a reliable, reproducible and simple viability
      assay for cartilage and osteochondral studies. The previous assays (radioisotope
      uptake, assessment of matrix components, histological methods, oxygen consumption
      etc.) were complex, laborious, time consuming or suffer from difficulty of
      interpretation. MTT assay was chosen because it has been widely and successfully
      used in different cell and tissue studies, but has not been published on human
      solid articular cartilage. Fresh intact cartilage samples of human tali were
      tested to investigate the assay. The reliability of the MTT assay was also tested
      by an fluorescent dye combination. The MTT assay is based on the production of
      purple formazan pigment from methyltetrazolium salt by the mitochondrial enzymes
      of viable chondrocytes. The enzyme kinetics of the reaction was also investigated
      because it was unknown in the case of cartilage. The amount of pigment formed can
      be measured by spectrophotometry after extraction by methyl cellosolve. The color
      density is proportional to mitochondrial enzyme activity, reflecting the number
      of viable chondrocytes. The optimal reagent concentration, biopsy size, and
      incubation period were established. There is a linear relationship between the
      cartilage weight and the pigment production activity. A 9.8% nonspecific raction
      was observed in the negative controls. The enzyme kinetics of the reaction was
      also investigated. The MTT clevage up to 0.1% (w/v) follows the Michaelis
      kinetics. We calculated the Michaelis constant (2835 +/- 130 microM), the maximal
      velocity (36 +/- 3.2 x 10(-5)microMsec(-1)) and the velocity constant (1.27 +/-
      0.2 x 10(-7)sec(-1)) of the reaction. The latter is a significant marker for each
      tissue type. The viability of cartilage was also assessed and calculated by a
      fluorescent dye combination comprising 1 microg/ml propidium iodide (PI) and 4
      microM/ml SYTO-16 stains. The PI stains dead cells (red fluorescence), the SYTO
      16 stains live cells (green fluorescence). The staining can be visualised
      simultaneously, and the live/dead ratio can be calculated by image analysis
      software from saved image files. The MTT assay is a simple, non-expensive,
      efficient, reliable, reproducible, sensitive viability test for cartilage
      studies. The MTT reduction assay and the staining method were corrobative.

PMID- 15256877
TI  - Banking of osteochondral allografts, Part II. Preservation of Chondrocyte
      Viability During Long-Term Storage.
AB  - One of the most important factors concerning the successful clinical outcome
      after transplantation of osteochondral allografts is the viability of the
      cartilage.The viability of cryopreserved cartilage is quite poor, 20-30% cell
      survival has been published. The purpose of this study was to develop a new
      storage method which improves the chondrocyte viability. The talus of cadaveric
      donors was used as a model tissue to compare human osteochondral allograft
      cartilage viability following cryopreservation with that remaining after
      prolonged refrigerated storage. Full-thickness cartilage punch biopsies had been
      cryopreserved, and tali were divided into two matched groups and stored in TCM
      for 60 days at +4 degrees C, either with or without regular medium replacement.
      The cartilage of each graft was biopsied and assayed for viability on every third
      day by the MTT reduction assay. During 4 degrees C storage, a recurring pattern
      of large fluctuations in apparent cartilage viability was observed in every
      stored graft, with or without medium replacement. These fluctuations did not
      appear in control specimens of either fresh or cryopreserved human skin that were
      assayed in parallel with the cartilage biopsies, so the viability fluctuation
      seems an intrinsic property of the cartilage in these conditions. Cartilage
      stored for 60 days at +4 degrees C showed significantly higher viability (35.2 +/
      3.3 %) than fresh cartilage that had been cryopreserved (21.6 +/- 1.8 %). This
      was true even when cryopreserved and thawed cartilage was subjected to a 3 day
      post thaw incubation under presumably favorable conditions (17.7 +/- 1.6 %).
      These viability assay results, (reflective of intracellular metabolic activity),
      were corroborated by the fluorescent dye mixture SYTO-16 and propidium iodide.
      The data indicate that long-term stored refrigerated cartilage appears to retain
      a viability higher than that of cryopreserved cartilage for up to and perhaps
      beyond 60 days of storage. There was no viability index difference between the
      medium replaced and non-replaced groups. Although an exceptional result, in one
      individual case, more than 65% viable cells could be detected in the talar
      cartilage after 60 days storage at +4 degrees C.

PMID- 15256878
TI  - Good results of circumferential spine fusion in smokers, using autograft and
      allograft.
AB  - We have examined the rates of anterior interbody fusion of lumbar spine segments
      following fusion with a fresh frozen femoral head allograft in 25 heavy smoking
      patients. They were all stabilized both anteriorly and posteriorly. The
      indications for surgery were: degenerative disc disease, degenerative
      spondylolisthesis and nonunion following previous posterolateral fusion of lumbar
      spine segments. Only patients who had fusion of one or two lumbar segments were
      included. They all were stabilized posteriorly with pedicle screws and autogenic
      iliac bone graft. The fusion was assessed at least one year after surgery
      according to plan X-rays as "Solid", "Questionable" or "Failure". One patient was
      found at follow up not fused, in another one the fusion was "questionable" and
      all the other 23 patients had an anterior solid fusion. Clinically, 84% of the
      patients had the same or improved work status as before surgery and 68%
      acknowledged that they were satisfied with the surgical results. No major
      complications were recorded and the average length of hospitalization was 10.3
      days.

PMID- 15256879
TI  - Long-term clinical experience with fresh osteochondral allografts for articular
      knee defects in high demand patients.
AB  - Fresh osteochondral allografts are used to repair osteoarticular defects of the
      knee. For post-traumatic defects recent advances in other techniques for
      cartilage repair and resurfacing have reduced the role of allograft tissue
      transplantation to defects larger than 3 cm in diameter and 1 cm in depth.A fresh
      osteochondral allograft that has been harvested from a donor within 24 h from
      death and preserved in 4 degrees C for up to 4 days shows 100% viability of the
      cartilage. The avascular bone remains structurally intact and mechanically strong
      until it is replaced by host bone or until it is weakened or absorbed. The
      indications for fresh osteochondral allografts for reconstructive surgery of the
      articular surface of the knee do not justify the use of immunosuppressive drugs
      and we therefore believe that surgical vascularization of the grafts should not
      be carried out.This clinical approach can provide a reconstructive solution for
      younger higher demand patients where implants are not desirable and arthrodesis
      is not acceptable. A clinical follow-up study as early as 1975 showed successful
      early outcomes. More recently, survival analysis found 95% survival at 5 years,
      71% at 10 years, and 66% at 20 years. It was learned that older patients, bipolar
      transplants, improper loading of the graft, and grafts for osteoarthritis and
      steroid-induced avascular necrosis do not lead to good long-term outcomes.We
      would like to describe here some of our long-term clinical experience concerning
      this surgery.

PMID- 15256880
TI  - Long term follow-up of reconstruction with allogeneic mandibular bone crib packed
      with autogenous particulate cancellous bone marrow.
AB  - Allogeneic mandibular bone processed by the deep frozen method was used as a
      biologic crib for mandibular reconstruction. The allogeneic mandible is
      biocompatible, bioresorbable, of low antigenicity and provides the morphology for
      symphysis contour, angle of mandible and dental arch form. The particulate
      cancellous bone marrow (PCBM) contains marked osteogenic potential of
      hematopoietic marrow, which promotes osteogenesis. The cancellous marrow graft
      lacks structure and requires a crib to house it during the bone regeneration to
      the consolidation phase. Fresh frozen mandible was hollowed out for packing with
      PCBM prior to securing it to the defect by a rigid fixation method. Four cases of
      large mandibular defects resulting from treatment of benign odontogenic tumors
      were reconstructed utilizing this technique. All cases showed excellent facial
      contour and function satisfactorily in mastication and pronunciation. Complete
      graft incorporation and restoration of the osseous continuities were observed for
      four to 12 years after the operation.

PMID- 15256881
TI  - The research potential of tissue from a cadaveric donor.
AB  - The purpose of this case report is to illustrate the research potential of the
      tissue obtained from a single donor referred to the Peterborough Hospitals NHS
      Trust (PHNHST) Research Tissue Bank. Tissue retrieval was done 19 hours after
      death and 453 tissue units processed on site were despatched to 20 mainly
      commercial client research organisations.

PMID- 15256882
TI  - Ethical issues relating to supply of human tissue to the commercial biomedical
      sector.
AB  - Demand for an ethical supply of human tissue for research in the commercial
      biomedical sector is increasing substantially. This article sets out to review
      ethical issues specifically relating to acquisition of tissue from patients in a
      publicly funded national health service (NHS), for research use in a commercial
      setting. Some of the background to recent high profile Inquiries in England is
      discussed and is used to illustrate legal and ethical differences between living
      and dead people. Issues relating to patient consent are investigated and the case
      is made for a clear distinction between tissue acquisition and tissue processing.
      Future possibilities for regulation are discussed.

PMID- 15256884
TI  - Editorial.

PMID- 15256883
TI  - Voice of associations.

PMID- 15256885
TI  - Processing of ovine cardiac valve allografts: 1. Effects of preservation method
      on structure and mechanical properties.
AB  - It is essential to have some method of preservation of allograft valves during
      the time between procurement and implantation. Cryopreservation is the most
      commonly-used storage method today but it has the major disadvantage of high
      cost, and because its aim is to preserve living cells only relatively gentle
      antimicrobial treatments are used. This study addresses two interrelated
      questions: Is it necessary to maintain living donor cells in the tissue graft?
      Can more effective measures be used to reduce the risk of transmission of
      diseases, especially viral diseases, via human tissue grafts. In this paper, we
      report an investigation of four preservation methods that could be combined with
      more effective disinfection: cryopreservation with dimethyl sulphoxide, storage
      at approximately 4 degrees C in a high concentration of glycerol as used for the
      preservation of skin, snap-freezing by immersion in liquid nitrogen and
      vitrification. Snap freezing was mechanically damaging and vitrification proved
      to be impracticable but two methods, cryopreservation and storage in 85%
      glycerol, were judged worthy of further study. Cryopreservation was shown to
      maintain cellular viability and excellent microscopic structure with unchanged
      mechanical properties. The glycerol-preserved valves did not contain any living
      cells but the connective tissue matrix and mechanical properties were well
      preserved. The importance of living cells in allograft valves is uncertain. If
      living cells are unimportant then either method could be combined with more
      effective disinfection methods: in that case the simplicity and economy of the
      glycerol method would be advantageous. These questions are addressed in the two
      later papers in this series.

PMID- 15256886
TI  - Processing of cardiac valve allografts: 2. Effects of antimicrobial treatment on
      sterility, structure and mechanical properties.
AB  - This is the second in a series of papers that report experiments to investigate
      the properties required for effective tissue valve implants. This paper is
      concerned with investigations into alternative antimicrobial treatments and the
      effect these treatments produce on the structural and biomechanical properties of
      ovine aortic valves. Six treatments were studied: heat, peracetic acid (at two
      concentrations), chlorine dioxide, a surfactant cleaning agent and a
      solvent/detergent treatment. Samples of myocardial tissue were exposed to a mixed
      bacterial culture or one of three virus cultures and then decontaminated. Two of
      the six treatments (0.35% peracetic acid and heat) were effective in removing
      both bacterial and viral contamination, reducing levels of contamination by 2.5
      to 3 logs, whilst a third (chlorine dioxide) was effective against viruses (
      approximately 3 log reduction). Valves subjected to these treatments were
      examined by microscopy and measurements of mechanical properties were made. All
      three treatments seriously damaged endothelial cells and leaflet fibroblasts.
      Heat treatment also damaged connective tissue components (collagen and elastin)
      but these changes were not seen after chemical treatment. Mechanical testing
      confirmed severe damage following heat treatment but chemical treatment showed
      only minor effects on the elasticity of the leaflets and none on extensibility.
      These minor effects could be mitigated by exposure to a lower dose of peracetic
      acid and this treatment could be safely combined with cryopreservation or storage
      in 85% glycerol. Peracetic acid was the preferred disinfection method for use in
      the subsequent in vivo studies in sheep.

PMID- 15256887
TI  - Processing of ovine cardiac valve allografts: 3. Implantation following
      antimicrobial treatment and preservation.
AB  - It is known that a satisfactory clinical outcome can follow the implantation of
      cardiac valve allografts in spite of the loss of living cells in the tissue. If
      viable cells are not required for long term graft function, then effective
      disinfection of the tissue might become possible. In an earlier paper in this
      series we reported that peracetic acid (PAA) is an effective antimicrobial agent
      for the treatment of valve allografts; it was lethal to the cells but at a
      concentration of 0.21% had little effect on the mechanical properties or
      extracellular morphology of the valve leaflets. It was also found that PAA
      treatment could be combined with storage in 85% glycerol at 4 degrees C, or
      cryopreservation with 10% Me(2)SO, without substantial further impairment of
      microscopic structure or mechanical properties. In this paper we describe the
      implantation of processed ovine aortic valves in the descending thoracic aorta of
      sheep. The experimental groups included control untreated valves and valves that
      had been treated with antibiotics or PAA and either cryopreserved, or stored in
      85% glycerol. The recipient sheep showed good clinical appearances until the
      experiment was terminated at six months. The explanted grafts were examined by
      standard morphological and mechanical testing methods. The PAA-treated valves
      were clearly recognisable as valves: the leaflets had fair to medium morphology
      in both the unpreserved and the cryopreserved groups. All leaflets had a
      superficial overgrowth of cells. Microsatellite analysis for allelic differences
      were performed on samples of donor and recipient tissues using three markers of
      tissue source. Only one valve, which had been treated with PAA, revealed allelic
      differences between donor and recipient. It is suggested that DNA-fragments may
      have remained after the destruction of donor cells and six months of
      implantation: the overgrowing cells were almost certainly of recipient origin. We
      conclude that our experiments, in which PAA-treatment was combined with
      preservation, are sufficiently encouraging to justify further studies to refine
      the technique, but in our opinion they are not sufficient to justify a clinical
      trial at this time.

PMID- 15256888
TI  - Ocular fixation with quadriceps tendon allograft.
AB  - Management of difficult strabismus, such as strabismus fixus and paralytic
      strabismus, in order to maintain the alignment is complicated. There are many
      surgical approaches described in the current literature, together with notes on
      the materials used to stabilize these deformities. We present a new surgical
      approach using quadriceps tendon allograft for the correction of difficult
      strabismus such as strabismus fixus and paralytic strabismus. Our idea for using
      deep frozen quadriceps tendons developed from the fact that this is the most
      stable and strongest tendon in the whole body. Six patients with strabismus fixus
      (n = 1), paralytic strabismus secondary to extraocular muscle damage (n = 1) and
      combined cranial nerve palsy (n = 4) were operated on using a strip of deep
      frozen quadriceps tendon allograft sutured onto both the globe and the
      periosteum. The mean age of the patients was 44.33 years. (range 17-71 years) All
      the patients were followed up for six months. The mean preoperative deviation in
      the six cases was 60 prism diopters (PD) (range 30-123 PD) The mean change in
      horizontal alignment at 1 month, 3 months and 6 months postoperatively was 54 PD,
      53 PD and 49.16 PD respectively. We had only one case of undercorrection. This
      may possible be due to the remaining function of the antagonist and/or the fact
      that we had used the distal end of the quadriceps tendon. When the patient
      (patient No. 5) who had 2 operations was excluded, the mean change in horizontal
      alignment was 48.6 PD, 47.4 PD and 43.6 PD. Post-operatively there was no
      infection or any other complications. According to our study of existing
      literature, these cases of deep frozen quadriceps tendon allograft application
      for the indications mentioned above are the first reported cases of its type. We
      conclude that ocular fixation with quadriceps tendon to the periosteum is a safe
      and effective option for the management of difficult strabismus. Further research
      on a larger cohort of patients and longer follow-up time are needed.

PMID- 15256889
TI  - Preliminary clinical experience with the preparation and therapeutic use of
      autologous osteoblasts and chondrocytes.
AB  - Particular results of autologous osteoblasts preparation from patient's bone
      marrow and autologous chondrocytes from cartilage, both for therapeutic
      application are given. Osteoblastic cells were cultivated from fresh bone marrow
      in the presence of dexamethasone in alpha MEM medium containing 10% of patient's
      and 10% of fetal bovine sera and other necessary additives without any cytokine
      stimuli. Alkaline phosphatase cell surface activity was used as a marker for
      quick osteoblastic phenotype confirmation. Autologous chondrocytes were
      enzymatically separated from fresh knee cartilage. Pieces of cartilage, 2 mm(3)
      in volume, were sufficient for live cellular graft preparation. Viability of
      chondrocytes obtained by this approach was more than 90%. In both cases, in
      osteoblasts as well as in chondrocytes, the amount of cells obtained during the 4
      week culture, was sufficient for clinical use.

PMID- 15256890
TI  - The establishment of a network of European human research tissue banks.
AB  - This is a report of a workshop held on the establishment of human research tissue
      banking which was held in Levi, Finland 21-24 March 2002. There were 21
      participants from 7 European countries. This meeting was attended by
      representatives from academia, research tissue banks and from the Biotech and
      Pharmaceutical Industries. The principal aim of the workshop was to find a way to
      progress the recommendations from ECVAM workshop 44 (ATLA 29, 125-134, 2001) and
      ECVAM workshop 32 (ATLA 26, 763-777, 1998). The workshop represented the first
      unofficial meeting of the European Network of Research Tissue Banks (ENRTB)
      steering group. It is expected that in the period preceding the next workshop the
      ENRTB steering group will co-ordinate the ethical, legislative and organisational
      aspects of research tissue banking. Key issues dealt with by the Levi workshop
      included the practical aspects of sharing expertise and experiences across the
      different European members. Such collaboration between research tissue banks and
      end users of such material seeks to ultimately enable shared access to human
      tissue for medical and pharmaco-toxicological research while maintaining strict
      adherence to differences in legal and ethical aspects related to the use of human
      tissue in individual countries.

PMID- 15256891
TI  - The expression of hepatitis-C virus antigen by immunohistochemical stain and
      polymerase chain reaction in corneas of seropositive corneal donors.
AB  - Background: Of the donor corneas rejected for transplantation, the largest group
      is that from donors testing seropositive for hepatitis C virus (HCV). In
      situations of severe shortage in supply of donor corneal tissue, we may consider
      the use of seropositive donors for transplantation if we can prove with high
      certainty the absence of HCV RNA in the donor corneal tissue. Polymerase chain
      reaction (PCR) is a highly sensitive and specific technique for direct detection
      of HCV RNA and can be used for this purpose. Nevertheless, it is not applicable
      for routine clinical use in most eye departments due to its unavailability and
      cost effectiveness. Purpose: To study the possible use of immunohistochemical
      method for detection of HCV antigen in corneal tissue of seropositive donors and
      correlate the results with those of PCR. Immunohistochemical methods have not yet
      been studied in donor corneal tissue. Materials and methods: Eight corneas of 4
      seropositive and 8 corneas of 4 seronegative corneal donors were studied by
      immunohistochemical and PCR methods for the presence of HCV antigen in their
      corneal tissue and sera. Results: HCV RNA was not detected in the sera and
      corneal tissue of all seropositive and seronegative corneal donors by either PCR
      and immunohistochemical methods. Conclusion: Although the study is too small for
      conclusive results, the correlation between the immunohistochemical and PCR
      studies for direct detection of HCV antigen in corneal tissue of seropositive
      donors may raise the possibility of using the immunohistochemical method for
      screening of donor corneas for the detection of HCV antigen. A larger prospective
      study investigating the sensitivity, specificity and clinical applicability of
      the immunohistochemical method is warranted.

PMID- 15256892
TI  - Editorial.

PMID- 15256893
TI  - The role of quality control in a skin bank: tissue viability determination.
AB  - New surgical procedures requiring viable skin have increased rapidly over the
      last few years. The cell viability assessment in allograft skin is a major step
      forward in burn treatment, since it is well-known that taking is correlated with
      grafted tissue viability. Various methods, both qualitative and quantitative, are
      currently used. Although qualitative assays (histomorphology,
      immunocytochemistry) are routinely performed in our laboratory, there arose a
      need to set up a standardised quantitative assay in an attempt to obtain a cut
      off value so that the skin sample could be determined valid or not for grafting.
      Therefore, two different tetrazolium salt compounds MTT and WST-1, were compared
      in order to determine their efficacy in the evaluation of tissue viability.
      Several experimental conditions were analysed: 1- cellular cultures of
      keratinocytes and fibroblasts, 2- fresh skin tissue samples, 3- the same specimen
      tested daily for at least 2 weeks, 4- after cryopreservation and thawing. Viable
      cells were analysed by the cleavage of tetrazolium salts to formazan by cellular
      enzymes. The formazan dye produced by metabolically active cells was then
      quantified by measuring the absorbance of the dye solution at the appropriate
      wavelength. It was seen that WST-1 is easier to handle, more stable, has a wider
      linear range, accelerated colour development and is more sensitive than MTT on
      fresh specimens and cell suspension. However, after 72 hours of storage at 4
      degrees C, most of the WST-1 tested specimens no longer gave any absorbance
      signal, whilst MTT specimens were seen to give a signal for more than two weeks.
      Moreover, after thawing WST-1 tested samples were almost negative, whilst MTT
      samples continued to give strong signals. In conclusion, WST-1 assay offers rapid
      and precise results as to the cell viability of fresh allografts and cell
      cultures, whilst the MTT method is much more useful in establishing viability
      after long conservation and cryopreservation. In our clinical experience,
      allografts transplanted at 72 hr post-harvesting or after cryopreservation showed
      a mean of take more than of 80%, demonstrating that the MTT system is more
      reliable for the determination of allograft viability. Studies are ongoing with
      larger clinical cohorts to establish the precise cut-off value for skin graft
      validation.

PMID- 15256894
TI  - The use of allogeneic cultivated keratinocytes for the early coverage of deep
      dermal burns - indications, results and problems.
AB  - Since 1995, keratinocytes are grown into cultures and used as allografts for the
      coverage of deep dermal defects in our burn unit. Donor skin samples are mostly
      acquired from other burn patients. In addition, special methods of skin
      preservation allow us the use of skin, which has been taken in redundancy for
      split thickness skin grafting from nonburned patients.Thirty five patients with
      deep partial thickness burns in the face were treated since 1996 according to the
      following concept: Dermabrasion or tangential excision was performed before the
      5(th) day following trauma. If viable dermis was present, the wounds were covered
      with sheets of allogeneic cultivated keratinocytes. In cases of deeper defects,
      autologous skin grafts were applied. In 23 cases, epithelialisation was achieved
      within 10 days, in 8 patients, a prolonged duration until complete healing was
      observed. In 5 faces, coverage of residual defects with skin grafts was
      necessary. The mentioned problems of wound healing occurred from infection,
      incomplete excision of burn eschar and a depth of the wound which was
      retrospectively seen too deep for the treatment with keratinocytes. At follow up,
      patients were examined clinically and functionally with Frey's faciometer(R),
      which is an instrument for quantification of mimic movements. In cases of
      uncomplicated healing, a nearly complete restitution was found.Other indications
      include deep dermal burns in children and the coverage of early excised wounds in
      adults, with a reasonable amount of viable dermis remaining, both resulting in a
      significant reduction of donor-site morbidity. In severely burned adults with
      limited donor sites, it offers the possibility of immediate definite coverage of
      large areas.

PMID- 15256895
TI  - Cultured epidermal allografts: Quantitative evaluation of their healing effect in
      deep dermal burns.
AB  - This study summarizes the Brno Burn Centre experience with the application of
      cultured epidermal allografts (CEAl) in the treatment of deep dermal burns. In a
      prospective randomised trial on 30 patients with deep dermal burns CEAl obtained
      from young healthy and examined donors and fixed on tulle grass carrier
      (Grasolind) were compared with empty Grasolind as the lowest layer of dressing.
      All the other layers were identical.Both kinds of dressing were applied
      simultaneously on the same deep dermal burn wound between 6th and 10th day after
      burn. Six days later the non-healed wound areas were recorded through painting on
      cellophane membrane and scanned in the computer. The percentage of wound
      reduction was calculated and statistically evaluated.The reduction of the non
      epithelialized wound area was 86.5% when covered through CEAl and only 71.2% when
      covered with tulle grass (Grasolind) only. This difference is statistically
      significant.In conclusion it can be stated that cultured epidermal allografts
      strongly stimulate reepithelialisation in deep dermal burns.

PMID- 15256896
TI  - Wound healing enhancement in leg ulcers: A case report.
AB  - Wound healing in the skin is a complex biological process in which numerous types
      of cells, cytokines, growth factors, proteases and extracellular matrix
      components act in concert to restore the integrity of injured tissue. Cultivated
      allogenic human keratinocytes have been used for the treatment of various skin
      defects like burnwounds, surgical wounds, in exfoliative skin diseases and
      chronic wounds. A new method for wound healing enhancement in leg ulcers using
      cultured allogenic keratinocytes suspended in fibrin glue and used in spray
      technique is introduced. Allogenic keratinocytes are supposed to enhance
      granulation tissue production and to stimulate reepithelisation due to their
      release of growth factors and thus are able to recreate an active wound.

PMID- 15256897
TI  - Prevention of burn wound conversion by allogeneic keratinocytes cultured on
      acellular xenodermis.
AB  - Deep dermal burns frequently tend to convert into full-thickness skin loss. We
      found that this wound deepening may be prevented by recombined human/pig skin
      (RHPS), consisting of human allogeneic keratinocytes cultured on acellular pig
      dermis. RHPS has skin-like consistency and therefore optimal adhesiveness to the
      wound. It can be easily removed from the dish and transferred to the recipient.
      The wound bed has to be prepared by tangential excision or deep dermabrasion to
      the level of capillary bleeding. RHPS has to be applied 'upside-down', with the
      epidermal layer facing the wound, to avoid the dermal matrix forming a barrier to
      the nutrients for the keratinocytes. In our practice, more than 70% of early
      excised or deeply dermabraded wounds grafted with RHPS healed in the course of
      one week after keratinocyte transplantation.

PMID- 15256898
TI  - Allograft reconstruction of the distal humerus after resection of a breast
      solitary metastasis: eleven years follow-up.
AB  - Resection is a rare indication for the treatment of solitary skeletal metastasis
      (SSM), and provides an opportunity to cure the oncologic patient. Reconstruction
      after resection can imply a difficult problem depending on the size and the
      location of the metastasis. In the reported case, an en-bloc resection of a SSM
      of a breast cancer located in the distal humerus was performed in 1990.
      Reconstruction of the osteoarticular defect has been achieved with a massive
      allograft. At eleven years follow-up the patient remains free of illness and
      shows a good functional result. With the result obtained in the reported case, we
      suggest that osteoarticular allograft can be of considerable value for
      reconstruction after excision of SSM in the distal humerus, and that cure can be
      achieved with the radical resection of a SSM of breast cancer.

PMID- 15256899
TI  - Long-term results of hemipelvic allograft: Report of four cases.
AB  - Reconstruction after the excision of pelvic tumors involving the pelvic ring
      implies difficult problems. Restoration of the function is difficult and an
      allograft can be one of the possible solutions. Pelvic allograft is recommended
      by many authors to reconstruct the pelvic ring following extensive resections of
      bone tumors. Between 1988 and 1989, we performed hemipelvic resection and
      allograft reconstruction in 4 patients with pelvic sarcomas. The mean age was
      42.3 years (range 38-48), consists of 3 male and 1 female. One case developed an
      infection and one case showed recurrence, both responding to surgical treatment.
      Outcome in those cases in which surgery was curative to the primary tumor was
      satisfactory at 10 years follow-up, with a mean total Enneking score of 25.3
      (range 24-27) and a good functional result in Merle D'Aubigne functional score.
      Despite the limited number of cases presented, our results added to the reported
      results in the literature led us to consider that allografts are valuable in
      pelvic reconstructions after en-bloc resections for bone tumors.

PMID- 15256900
TI  - Devastating endophthalmitis caused by Serratia marcescens in two recipients after
      transplantation of corneal grafts from the same donor.
AB  - We report two cases of severe endophthalmitis, which were caused by Serratia
      marcescens, and developed in the immediate postoperative period in two recipients
      of corneal grafts from the same donor. The cause of the donor's death was massive
      CVA. He had been on mechanical ventilation for 12 days before he died, and had
      shown no sign of infectious disease while in the hospital. Vitrectomies were
      performed in the recipients' eyes on the third day after corneal transplantation.
      On the same day, and again 1day later, the transplanted eyes were injected
      intravitreally with vancomycin and ceftazidime. Two months after surgery, both
      eyes developed phthisis. These cases are similar to other rare reported cases
      describing the virulence of S. marcescens.

PMID- 15256901
TI  - Utilisation of bone allograft by orthopaedic surgeons in Scotland.
AB  - The use of bone allograft in orthopaedic surgery has been predicted to increase,
      particularly in joint revision surgery. This has led to a potential problem with
      supply. Questionnaires were distributed to all 146 Consultant Orthopaedic
      surgeons working in Scotland in 2000. They were asked to indicate their current
      usage of bone and tissue allograft, any problems encountered with supply and if
      alternatives to allograft, such as processed bone, might be used. The questions
      asked were very similar to those asked in a previous study in 1995 to enable
      comparisons to be made. Replies were received from 125 Consultants (87%) of whom
      93 reported using bone allograft. Forty-one consultants (46%) predicted an
      increase in their requirement for bone allograft, and 23 (26%) felt they could
      currently use more bone if this was available. Sixty percent of surgeons would
      consider using processed bone as an alternative. In comparison with figures from
      1995, an increasing number of surgeons are prepared to use processed bone as an
      alternative to fresh frozen allograft.

PMID- 15256902
TI  - Regional program for bone allograft harvesting following multiorgan procurement
      in Pomeranian Academy of Medicine in Szczecin.
AB  - In Poland, up to 1999, the bones for allograft preparations had been procured
      only in mortuaries of forensic medicine departments. The increasing demand for
      bone transplantations greatly exceeds the supply resulting in a long waiting time
      for bone allografts. In November 1999, for the first time in Poland, the group of
      orthopedic surgeons from the Pomeranian Academy of Medicine started the regional
      program for bone harvesting following vascularized organ procurements. The aim of
      this paper is to present the technical details and limitations of bone harvesting
      that occurred in 10 out of 25 multiorgan procurements.

PMID- 15256903
TI  - Comparison of the efficacy of virus inactivation methods in allogeneic avital
      bone tissue transplants.
AB  - Several procedures for inactivating viruses are used presently in the context of
      bone tissue transplants. Common methods used are gamma irradiation (25 kGy),
      treatment with moist heat (82.5 degrees C/15 min., lobator-sd2-system) as well as
      chemical sterilisation using peracetic acid-ethanol treatment (PES, 2% peracetic
      acid, 96% ethanol, Aqua [2:1:1], 200 mbar, agitation, 4 hours). Based on national
      and international guidelines, we tested the antivirucidal effectiveness of these
      methods in human bone transplants. Three enveloped viruses: human
      immunodeficiency virus type 2 (HIV-2), pseudorabies virus (PRV), bovine virus
      diarrhoea virus (BVDV), and three non-enveloped viruses were used: hepatitis A
      virus (HAV), poliovirus (PV-1), porcine/bovine parvovirus (PPV, BPV). Defatted
      spongiosa cuboids served as model in chemical treatment experiments, while
      cortical diaphyses were used in gamma irradiation experiments, and the effects of
      thermal treatment were tested in prepared femoral heads. The log(10) reduction
      was measured by cytopathogenic effects after virus titration (TCID(50)/mL). A
      dose of at least 33.9 kGy (bone model) at -30 +/- 5 degrees C was necessary to
      achieve a sufficient reduction (4 log(10) steps) of BPV, the most resistant one
      of all viruses investigated. Thermal treatment as well as PES treatment led to a
      reduction of virus titres by more than 4 log(10). Only HAV showed a reduction
      below 4 log(10) (2.87) with PES. After validation of the defatting step included
      for HAV-infected cells, a HAV-reduction of over 7 log(10) was found. All three
      sterilisation methods tested are recommended for bone transplant sterilisation,
      but only provided that additional safety measures (anamnestic informations,
      infectious serology, PCR in case of multiorgan donors) are taken.

PMID- 15256904
TI  - Improved islet survival and in vitro function using solubilized small intestinal
      submucosa.
AB  - In vitro proliferation of isolated pancreatic islets has become an area of great
      interest given the scarcity of clinical islet donors and the islet mass
      requirements for clinical islet transplantation. Small intestinal submucosa
      (SIS), a naturally occurring extracellular matrix, has been investigated to
      promote wound healing, tissue remodeling and cell growth. This study evaluated
      recovery and function of isolated canine pancreatic islets following in vitro
      tissue culture. Pancreatic islets were isolated from mongrel dogs using standard
      surgical procurement followed by intraductal collagenase distension, mechanical
      dissociation and EuroFicoll purification. Groups of purified islets were cultured
      in a humidified atmosphere of 95% air and 5% CO(2) for 48 hours in standard islet
      culture conditions of CMRL 1066 tissue culture media (Gibco) which had been
      supplemented with 25microM HEPES, penicillin/streptomycin and either 10% heat
      inactivated fetal calf serum (FCS, Gibco) or solubilized SIS solution (Cook
      Biotech, Inc., West Lafayette, IN). The mean recovery of islets following the
      culture period was determined by sizing duplicate counts of a known volume and
      viability was assessed by static incubation with low glucose (2.8 mM), high
      glucose (20 mM) and high glucose solution supplemented with 50 microm IBMX
      solution. Remaining islets were embedded histologically. From a consecutive
      series of six culture experiments, a significantly higher (p < 0.05) recovery of
      islets co-cultured with SIS was observed when compared to controls. Mean islet
      recovery was 84.5 +/- 2.9% (mean +/- SEM) from the SIS cultured group compared
      with 64.7 +/- 4.5% from the control group cultured in FCS (p < 0.05, n=6). Islets
      from the SIS treated group exhibited a significantly higher (p <, 0.05) insulin
      response to the high glucose stimulus than islets cultured in the standard FCS
      cultured solution. The calculated stimulation index was 12.3 +/- 3.4 for the SIS
      treated group compared with 5.6 +/- 1.8 for the standard cultured group (p <
      0.05). The overall mean numbers of islets recovered following in vitro culture
      was also higher in the SIS-treated group. The proportion of islets with a mean
      diameter >150 microm increased from 24% to 31% in the SIS-treated group, whereas
      the same proportion decreased to 18% from 22% in the control (FCS-treated) group.
      Histological evaluation of fixed tissue samples collected following the culture
      period identified insulin and glucagon-secreting cells in the SIS and FCS treated
      groups, however a higher frequency of insulin positive cells were detected
      consistently in the SIS treated group. A proliferation marker (PCNA) identified
      positive cells within both groups as well. This study suggests that co-culture of
      freshly isolated canine islets in medium supplemented with solubilized SIS can
      improve the post-culture recovery and in vitro islet function. Future
      investigations will focus on the cellular interactions of SIS, both in vitro and
      in vivo.

PMID- 15256905
TI  - In vitro cytotoxicity testing of coladerm membrane.
AB  - At present, biodegradable and biocompatible membranes based on collagen and
      glycosaminoglycans play an important role in substitutive medicine. Modern
      biomaterials use a chemically modified collagen-based matrix for implants with
      programmable biodegradability as a substitute of buccal mucosa, skin, cartilage,
      etc. Besides the requirements for biocompatibility and biodegradability, the
      membranes must be also non-toxic. Therefore, cytotoxicity testing of these
      materials in vitro is an integral part of introducing newly developed types of
      membranes into clinical practice. As a biological model for the tested COLADERM
      membrane, cell cultures from human embryonic fibroblasts (B-HEF-2) were used for
      both cytotoxicity testing as well as in tests to assess the ability of cells to
      proliferate on this membrane. Along with the ability of cells to grow on the
      surface and inside the membrane, immunohistochemical examination and scanning
      electron microscopy (SEM) were performed as well. The obtained results have shown
      that the COLADERM membrane is non-toxic with suitable structural and biological
      properties for clinical application as a substitute of buccal mucosa following
      surgical ablation of malignant tissues from the oral cavity.

PMID- 15256906
TI  - Inception and Five-year Run of a Semen Cryobank. Clinical and Behavioral Aspects.
AB  - Recent developments in infertility treatment, as well as medical and ethical
      concern to preserve the fertilizing ability of male subjects potentially at risk,
      led to the inception of a sperm cryobank in our medical center in 1996. Up to the
      end of the year 2000, 64 young men displaying higher semen values than generally
      required were accepted as donors, while 305 married (mean age 32.5, range 22-54)
      and 381 single women (mean age 41.2, range 27-50) were treated by artificial
      insemination donor (AID), resulting in 251 conceptions. Besides, 437 male
      subjects aged 15-61 requested sperm cryopreservation. Methodological
      considerations about sperm cryopreservation, and behavioral implications
      therefrom, are evaluated.

PMID- 15256907
TI  - Application of Banked Autologous Mucosal Cells to Graft Large Intraoral Mucosal
      Defects.
AB  - Purpose: This study was aimed to investigate the conditions that affect the
      generation of autologous cultured mucosal grafts (CMG) to promote their clinical
      application for large intraoral defects, following surgical excision of mucosal
      pathology. Specific parameters studied were the effect of patient's age and cell
      banking on the in vitro development of CMG, and on their clinical performance in
      vivo.Patients and methods: Twelve patients (10 M, 2F; mean age of 50.7+/-14.3
      years) with intraoral mucosal pathologies were included in this study. Autologous
      mucosal cells derived from 0.2-0.5 cm(2) biopsies, taken from clinically normal
      oral mucosa, were cultured in vitro and banked, as cell suspensions, in liquid
      nitrogen. Two to three weeks before the scheduled surgery, multilayered CMG were
      developed according to the anticipated area of the excised tissue (8-100 cm(2)),
      from banked or proliferating autologous cells (for 7/12 and 5/12 patients,
      respectively). Following excision, CMG sheets were placed on the mucosal defects
      and anchored to the adjacent tissue with sutures, which were removed a week
      later.Results: Both the production of CMG, and their clinical performance were
      unaffected significantly by patient's age. Three weeks postoperatively, the
      grafted sites were smooth and keratinized, without infection or scar contraction,
      with complete and comparable healing among the two groups, treated with banked
      and non-banked cells.Conclusion: This study indicates that CMG is a proper
      dressing for large intraoral mucosal defects of various etiologies, for a large
      range of patients' age, using either banked or non-banked cells.

PMID- 15256908
TI  - Skin Donors Positive for HBV Core Antibodies - to Bank or Not to Bank? An
      Overview from a Regional Tissue Bank.
AB  - A prompt transplantation of skin allografts on patients with severe, large body
      area burns is a preferred treatment, but depends on a suitable supply of tissue
      donors. Limiting factors include donors' identification, families consent, and
      following the standards - exclusion due to assessed transmissible diseases. To
      increase the current rate of skin donations to our regional skin bank, we
      reviewed the data of all potential organ donors, identified at Soroka University
      Medical Center from October 1997 to December 2000 and evaluated the causes for
      exclusion, especially due to HBV serological profile. 114/168 (67.9%) patients
      did not meet the indicated standards for organ donation, among which 20/114
      patients (17.5%) positive for anti-HBc (anti-HBc(+)). 54/168 persons were
      declared brain dead, with consents obtained from 21 families. To discuss the
      intriguing approval of skin from potential donors with anti-HBc(+) serology, the
      literature was reviewed, specifically - the reported outcomes of organ
      transplants from anti-HBc(+) donors, updates of HBV and skin, available tests,
      and finally a look for a safe commendable algorithm. The results suggested that
      HBV might be replicating in the skin, but proven communication of HBV has not
      been reported following grafting skin from anti-HBc(+) donors. Unlike other
      procured organs and tissues, grafted banked skin is a temporary cover, storable
      up to six years, under appropriate conditions. Hence, banking of skin from anti
      HBc(+) donors might be considered for future grafting of patients with identical
      serological profiles, presumably immune to a subsequent HBV infection, until a
      further re-evaluation of the standards. This procedure is anticipated to increase
      the potential of organ and tissue donations, specifically skin.

PMID- 15256909
TI  - Donation transplants and tissue banking in Mexico.
AB  - Knowledge about transplants in Mexico goes back to the Aztec period. Today the
      need for organ and tissue transplants in Mexico is high; the estimated number is
      100,000 patients, but there are only 2 donors per million population, for
      corneas. The organ, tissue and cell transplantation law which was modified in
      2,000, establishes that when a person dies, he will be a potential donor of
      organs and tissues. This new law will give hope to many patients, since it is
      expected to increase significantly the amount of organs and tissues for
      transplants. At present Mexico has 178 hospitals that are authorized to carry out
      organ and tissue transplants, and 53 Tissue Banks.

PMID- 15256910
TI  - Enrichment of non-apoptotic human spermatozoa after cryopreservation by
      immunomagnetic cell sorting.
AB  - Cryopreservation increases the rate of apoptotic spermatozoa with decreased
      capability to fertilise oocytes. In order to optimise the fertilisation rates,
      especially in assisted reproduction the use of apoptotic sperms should be
      avoided. Early events of apoptosis in cryopreserved spermatozoa are not
      detectable by conventional methods. However, the surface of apoptotic spermatozoa
      is characterised by externalisation of phosphatidylserine (PS), which has a high
      affinity to Annexin V. Therefore, colloid paramagnetic Annexin-V-conjugated
      microbeads (AN-MB) were tested for their ability to eliminate apoptotic
      spermatozoa from a total of 40 fresh and in TEST yolk buffer cryopreserved semen
      samples which were provided by 15 healthy volunteers. By passing through a
      magnetic field (MiniMACS, Miltenyi Biotec) the sperm suspensions were divided
      into 2 sperm fractions depending on bound magnetic Annexin V-microbeads (AN-MB)
      to spermatozoa. As additional markers of apoptosis CD95 (Fas, APO-1) on the sperm
      surface and activated caspases in the cytosol were detected in both fractions.
      Supplementary investigations comprised eosin-supravital staining and computer
      assisted sperm motion analysis. The separation was supervised by flow cytometric
      analysis of spermatozoa labelled with FITC-conjugated anti Annexin V-antibodies.
      Analyses of the magnetic inactive sperm fraction (AN-MB-negative) showed CD95 on
      0.6 +/- 0.3% (X +/- SEM) of spermatozoa and only 3.2 +/- 0.5% were stainable with
      eosin, whereas, 40.6 +/- 6.7% of the remaining cells in the column appeared to be
      CD95 positive and 99.8 +/- 0.1% stainable with eosin after cryopreservation.
      Indeed the overall amount of CD95 positive spermatozoa did not significantly
      increase after cryopreservation (2.5 +/- 0.5% vs. 4.3 +/- 1.2%; p > 0.05).
      Activated caspases were found in 21.8 +/- 2.6% of the spermatozoa in fresh and in
      47.7 +/- 5.8% of cryopreserved semen samples (p < 0.01). The separation procedure
      of the cryopreserved spermatozoa reduced significantly the quantity of those
      containing activated caspases to 9.3 +/- 2.2% within the AN-MB-negative fraction.
      In contrast 89.1 +/- 2.3% of AN-MB-positive sperms showed activation of these
      proteolytic enzymes. Flow cytometric analyses using FITC-conjugated anti Annexin
      V-antibodies for monitoring of AN-MB-binding to spermatozoa showed 5.2 +/- 1.0%
      labelled spermatozoa in the AN-MB negative fraction and 72.6 +/- 2.7% labelled
      spermatozoa in the AN-MB positive one. There was no significant influence of the
      separation column and the magnetic field on the sperm functions. The passage
      through the column led to a sperm loss of 0.8 +/- 1.2%. Conclusion: The binding
      of paramagnetic Annexin V-conjugated microbeads is an excellent method to
      eliminate spermatozoa at early apoptotic stages from cryopreserved semen samples.
      A deleterious influence of the separation column and the magnetic field on the
      spermatozoa was not observed.

PMID- 15256911
TI  - Biocompatibility studies of modified collagen/Hyaluronan membranes after
      implantation.
AB  - Two varieties of collagen/sodium hyaluronan membranes were used as dermal
      substitutes in a biocompatibility implantation study on rats. In order to improve
      especially the physical and mechanical properties of the material, the membranes
      were chemically modified using a combination of hexamethylenediisocyanate (HMDC)
      as a crosslinker and polyoxy-ethylene (POE) as a spacer. According to both
      macroscopic and microscopic histological observations, the membranes were well
      accepted by the surrounding host tissue in all the animals. No major differences
      in relation to the outgrowth of the material by host tissue have been observed
      between the implant varieties A and B. The most important finding was that no
      pathological changes or important alterations of the host tissues were detected.

PMID- 15256912
TI  - Human demineralised bone matrix as a bone substitute for reconstruction of cystic
      defects of the lower jaw.
AB  - In a retrospective study validated by a standardized clinical and radiological
      examination, the bone regeneration in 90 patients with cystic mandibular defects
      was examined. In 50 patients bony defect reconstructions with human demineralised
      bone matrix (HDBM) were carried out, while in a comparable group of 40 patients
      the hollow pockets were left to regenerate bone spontaneously. The bone
      regeneration after the implantation of human demineralised bone matrix (HDBM) was
      subjected to a comparative validation. Osteoinductive proteins present in HDBM
      (bone morphogenetic proteins) can diffuse into the implant seat and induce new
      bone formation (osteoinduction). A markedly faster and more thorough bone
      regeneration was demonstrated after the surgical therapy of cystic mandibular
      lesions with HDBM than without. HDBM also proved to be exceptionally
      biocompatible.

PMID- 15256913
TI  - Further evaluation of amniotic membrane banking for transplantation in ocular
      surface diseases.
AB  - Objective: To define the best conditions for amniotic membrane preparation,
      storage and banking in its use for corneal reconstruction. Methods: Amniotic
      membrane pieces were prepared under sterile conditions from placentas selected on
      the basis of donor medical and social history, serology, microbiological tests
      and histology. The pieces were kept at -140 degrees C but before grafting they
      were thawed and stored at 4 degrees C in RPMI medium, to have a preparation
      usable within 72 h. This procedure was validated by testing its therapeutic
      effectiveness in 25 patients 13 of which had corneal ulcers of various origin, 3
      had sequelae of herpes simplex keratitis, 3 band keratopathy and 6 corneal stem
      cell deficiency due to chemical or thermal burns. Results: The preparation showed
      appreciable anti-inflammatory and analgesic effects. In the absence of corneal
      stem cell deficiency a stable re-epithelialisation was achieved in 15 out of 19
      patients. When the limbus was lesioned, the amniotic membrane decreased
      vascularization and increased the number of corneal epithelial cells only in 1 of
      the 6 patients. No adverse reactions attributable to the tissue were recorded.
      Conclusions: A ready-to-use amniotic membrane preparation stored at 4 degrees C
      after cryopreservation has been tested in corneal reconstruction. Like the
      amniotic membrane thawed immediately before grafting, this preparation displayed
      full therapeutic effect in epithelial defects with stromal ulceration but without
      severe limbal stem cell deficiency. In two years banking activity 463 pieces of
      the preparation were successfully distributed to 90 Italian hospitals.

PMID- 15256914
TI  - In vitro reconstruction of full thickness human skin on a composite collagen
      material.
AB  - Rapid progress of in vitro techniques in the last years enabled the creation of
      organotypic skin cultures offering new possibilities in wound treatment.
      Rebuilding of graft is one of the key elements of successful outcome of the
      procedure. In search for the best scaffold for organotypic skin culture, the
      novel composite xenogenic collagen based material with unique properties has been
      created and used to reconstitute full thickness human skin in vitro. Based on our
      long established technology used for the production of collagen dressings for the
      treatment of burns, this novel, composite material offers excellent growth
      support of highly biodegradable spongy layer, combined with mechanical strength
      of collagen membrane. The modulation of collagen properties was accomplished by
      consecutive treatment with high temperature and gamma irradiation. The use of the
      substrate enabled to obtain organotypic culture that resembles full thickness
      skin with fibroblasts layer and well-developed multilayer epithelium. Our new
      material offers easy handling of obtained graft during surgery along with
      accelerated cell growth and controlled biodegradation of the culture support.

PMID- 15256915
TI  - 40 years of tissue banking in Estonia.
AB  - A survey is given of the development of tissue banking in Estonia during 40
      years, in which we address methods of tissue preservation, application of
      preserved skeletal tissues in orthopaedics as well as issues of clinical and
      experimental research in this area. Preparation and use of demineralized and
      morselized bone allografts has been significant during the last ten years.
      Progress of endoprosthetic joint surgery has essentially increased the need for
      bone transplantation in orthopaedics.

PMID- 15256916
TI  - Bone bank service in Odense, Denmark. Audit of the first ten years with bone
      banking at the Department of Orthopaedics, Odense University Hospital.
AB  - There has been an increase in the demand for allograft bone in recent years. The
      Odense University Hospital bone bank has been in function since 1990, and this
      paper outlines our results during the 10 year period 1990-1999. Potential donors
      were screened by contemporary banking techniques which include a social history,
      donor serum tests for HIV, hepatitis B and C, and graft microbiology. The bones
      were stored at -80 degrees C. No type of secondary sterilisation was made. 423
      femoral heads were approved and donated to 300 patients,1-6 heads/operation. The
      allografts have been used mainly to reconstruct defects at revision hip
      arthroplasty (34%), and for fracture surgery (24%). 7 % of all transplanted
      patients were reoperated because of infection. In the hip revision group the
      infection rate was 4 %. There were no cases of disease transmission. During the
      10 year period there was a change in the clinical use of the allografts. In the
      first years the allografts were mainly used for spinal fusion surgery, but today
      the majority are used in hip revision and fracture surgery. The clinical results
      correspond to those reported in larger international series.

PMID- 15256917
TI  - Demineralized Bone Matrix-stimulated Bone Regeneration in Rats Enhanced by an
      Angiogenic Dipeptide Derivate.
AB  - A lysyl-proline derivate (LP) known to stimulate angiogenesis and formation of
      granulation tissue was tested as a local additive to allogeneic demineralized
      bone matrix (DBM) using a rat craniotomy model. Peracetic-acid sterilized DBM (10
      mg/defect) was implanted into three groups of 45 animals each with 0, 6 and 20
      microg LP. Subsequent evaluation was done by descriptive histology,
      histomorphometry, and determination of the calcium content of the explants 7, 14,
      28, 42 and 84 days post-implantation. Grafting with DBM alone resulted in defect
      bridging by newly formed bone with incorporated DBM residues on day 84. Addition
      of LP to the implants caused an enhanced capillarization on day 14 and 28 as well
      as an enhanced mineralization on day 14, 28, 42 and 84. Both effects were dose
      dependent. These data suggest that the local application of a synthetic
      angiogenic factor significantly improve bone regeneration in DBM-grafted trephine
      defects in rats. Thereby, they reinforce the opinion that early angiogenesis is
      crucial for a number of subsequent events in the bone regeneration process.

PMID- 15256918
TI  - Validation of bone conversion in osteoconductive and osteoinductive bone
      substitutes.
AB  - Bone reconstruction can be performed with an autogeneic graft from various donor
      regions. Osteoconductive and osteoinductive bone substitutes originate from
      substances of diverse chemical and morphological types and can have a synthetic
      or a biological derivation. Alongside autogeneic bone transplants and allogenic
      and xenogeneic bone implants, alloplastic bone replacements of synthetic or semi
      synthetic origin are being used for defect reconstruction. In an animal model in
      rabbits five bone substitutes and one autogeneic graft were surgically
      incorporated into identical bone defects (10times 10 mm in size) in six
      anatomically defined regions of the skull. With scintigraphic and histological
      methods, the metabolic dynamics of the bone is examined as it reacts to the
      transplantation of autogeneic bone or to implanted bone replacement material.The
      different autogeneic, xenogeneic and alloplastic bone replacement materials can
      be differentiated according to the functional quality of the new tissue and the
      dynamics of the bone conversion thus induced. In the comparison of mineralized,
      osteoconductive bone subsitutes (TCP, HA, calcium carbonate ceramics) with
      demineralized, osteoinductive implants (DBM new, DBM old) and autogeneic bone
      grafts, the bone inducing matrices show the largest quantity of new bone
      formation, making possible a volume-constant reconstruction.

PMID- 15256919
TI  - A Pilot Study Evaluating Sodium Hyaluronate as a Carrier For Freeze-dried
      Demineralized Bone Powder.
AB  - Freeze-dried demineralized bone (FDDB) is widely used in orthopaedic and
      neurosurgery. However, it is difficult to deliver the FDDB by itself and surgeons
      have been seeking a convenient and easy-to-use form of FDDB. This study was
      designed to evaluate sodium hyaluronate (HA) as a carrier or delivery vehicle. HA
      is a viscous and biocompatible high molecular weight hydrogel. It was tested as a
      viscous carrier to facilitate the delivery of freeze-dried demineralized bone
      into a bony defect. The natural bone forming properties of FDDB were evaluated in
      an athymic mouse model and shown to be as active when dispersed in HA as compared
      to a saline control. Particle sizes in the range studied (125-850 microm) had no
      effect on FDDB efficacy. All exhibited active bone formation. Similarly, two
      different carrier viscosities were formulated to achieve both a malleable putty
      and a more flowable paste. These, too, both exhibited active bone formation. The
      use of a pH 7.4 buffer in the HA formulation gave optimum results in the model.
      Additional studies are underway to further evaluate the surgical efficacy of FDDB
      suspended in HA.

PMID- 15256920
TI  - Physical changes of amniotic membranes through glycerolization for the use as an
      epidermal substitute. Light and electron microscopic studies.
AB  - Our Department of Plastic and Reconstructive Surgery has routinely been using
      amnion preserved in glycerol for the treatment of debrided II degrees burns. This
      treatment is almost pain free and requires fewer changes of dressings and fewer
      anaesthetics. It also prevents overgrowing granulation tissue and lessens
      scarring.Since 1910 amnion has been used as biological wound dressing. Its
      advantages such as reduced loss of protein and electrolytes, fluids and energy as
      well as reducing the risk of infection and accelerated regeneration of the
      epithelium have been well documented in medical literature.In order to more
      closely examine the question of possible changes to the micro structure of the
      amnion through preservation and rehydration as well as the interaction between
      transplanted tissue and recipient, we have carried out several light and electron
      microscopic studies.Results showed that neither the treatment with glycerol, nor
      the pretransplantation rehydration eliminates the monolayer of surface epithelium
      of the amnion. Its complex architecture remains intact during the preservation
      process and is therefore suitable as a matrix for the growth of keratinocytes and
      thereby the healing process.In clinical use we found amnion to be an excellent
      wound dressing as it allows proper control of fluid, has sufficient permeability
      for gases, has good thermal properties, is impervious to micro-organisms and is
      free from toxic material.

PMID- 15256921
TI  - Preserved tissue allografts in reconstructive surgery.
AB  - Results of treatment with three various kinds of allografts: lyophilized bone,
      deep frozen bone and cartilage preserved in physiological solution, all of them
      radiation-sterilized are presented. We believe that this presentation may be
      helpful in estimating the tissue bank's allografts and in establishing
      indications and contraindications in the application of allografts in surgery.The
      'indices of coincidence' were compared in a group of 1014 patients after bone
      (lyophilized and radiation-sterilized) transplantation. It seems that such a
      variable as 'rebuilding of graft' may be of prognostic value in analysing the
      results of treatment in this group.The application of frozen and radiation
      sterilized allogenic bone grafts for reconstructions is also described. An
      analysis of the results of treatment in 1125 patients reveals that the use of
      preserved bone reduces the extent and duration of surgery. Almost total
      substitution of grafts may be seen in 3-8 months after surgery.Allogenic,
      preserved cartilage is often used in facial reconstructions of face. Human costal
      cartilage, preserved in 0.9% NaCl and radiation-sterilized, was used for
      reconstruction. The patients were examined 24-190 months after surgery (in
      several clinical units) and results were collected in a special questionnaire by
      the team that performed surgery. In an analysed group of 437 patients after
      cartilage transplantation, 42.2% were operated because of posttraumatical
      changes, 29.0% because of congenital malformations and in 16.7% non-specific
      inflammations were the cause of reconstructive operations. Malformations were
      located mainly in the nose (59%), the ear concha (16.5%) and 10.9% were
      mandible.The results of treatment were compared with ages of patients, diagnosis
      and the locations of the changes. Very good results were achieved in 33.5% of the
      patients, and satisfactory in 41.8% of the patients. However, in 19.9% of the
      patients the result of treatment was unsatisfactory. Correlation between some
      clinical and biological characteristics and the result of treatment is under
      discussion.

PMID- 15256922
TI  - Our Clinical Experience using Cryopreserved Cadaveric Allograft for the
      Management of Severe Burns.
AB  - Human cadaveric allograft is the most commonly used alternative wound closure
      material for excised burn wounds when limited donor sites or the overall patient
      condition does not permit immediate grafting with autologous skin.The Skin Bank
      in Singapore has supplied a total of 33,000 cm(2) of cryopreserved cadaveric
      allograft to the Burns Centre in Singapore for the early post-burn treatment of
      17 severely burned patients with body surface area (BSA) burn wounds averaging
      58% (range 33-90). An average of 13% (range 3-30%) cadaveric allograft was
      transplanted on 17 patients. Seven patients had recovered from their burn
      injuries and ten patients died of multiple complications related to their burn
      injuries. Our clinical observation has shown good adherence of cadaveric
      allograft when applied on clean and debrided wound bed after 4-7 days of post
      operation.The availability of cadaveric allograft permits early excision and
      wound coverage before the patients' condition is further compromised. Our
      clinical experience using cryopreserved cadaveric allograft is proving to be
      indispensable in the management of patients with severe burns.

PMID- 15256923
TI  - Letter from the editor.

PMID- 15256924
TI  - Biological Healing of Large Diaphyseal Deep-frozen Allograft Transplants.
AB  - The biological healing of large, deep-frozen, diaphyseal allografts was studied
      in 24 cats. Deep-frozen allograft stored at -80 degrees C was used to replace a
      large defect, at least two-thirds of the cat's tibial diaphysis. Intra-medullary
      rod fixation was used. The healing was studied at observation periods of 4, 6, 8,
      12, 16, 24 and 36 weeks. Biological parameters studied included microangiography
      for revascularisation and fracture healing, bone resorption, new bone formation
      and callus encasement. Deep-frozen allografts united without difficulty by 12
      weeks. However, minimal revascularisation of the allograft occurred even at 9
      months. Likewise, minimal biological repair activity was seen even at 9 months as
      shown by the parameters of bone resorption, cortical new bone formation and
      'callus encasement'. Biologically, deep-frozen cortical allografts remained inert
      for a long period of time in the adult cat.

PMID- 15256925
TI  - Improved human sperm recovery using superoxide dismutase and catalase
      supplementation in semen cryopreservation procedure.
AB  - The aim of this work was to evaluate the effects of ROS scavenger supplementation
      in human semen samples undergoing cryopreservation procedures.After screening out
      andrological pathologies, we selected 25 male partners of infertile couples with
      the following semen profile: volume >/= 2.0 ml, normal viscosity, sperm count
      >/=20 x 10(6)/ml, straight progressive motility (classes 1 and 2) >/= 40%
      (Mazzilli, Rossi, Delfino and Nofroni (1999) Andrologia 31: 187-194), atypical
      forms </= 70%, WBCs < 1.0 times 10(6)/ml.After liquefaction, standard semen
      analysis and the Hypoosmotic Viability Test (HVT) were carried out; the samples
      were then divided into 4 aliquots. The first was untreated as a control; 200 U/ml
      of superoxide dismutase (SOD) was added to the second, 200 U/ml of catalase to
      the third and both SOD (100 U/ml) and catalase (100 U/ml) were added to the
      fourth aliquot. Each aliquot was mixed (v/v) with TEST yolk buffer freezing
      medium (Irvine Scientific) and then frozen at -196 degrees C. The percent
      recovery of progressive motile and swollen spermatozoa was evaluated after
      thawing.No significant variation in the recovery of progressive motility was seen
      in the aliquots with added SOD or catalase alone, compared to the control group.
      On the other hand, a significant improvement in sperm parameter recovery was seen
      in the aliquot with both SOD and catalase supplementation; perhaps because of
      their combined and simultaneous action on superoxide anion and hydrogen peroxide.
      These results suggest that, in some selected cases, SOD and catalase
      supplementation can contribute greatly to the prevention of sperm membrane lipid
      peroxidation by ROS and thus allow good sperm parameter recovery after freezing
      thawing procedures.

PMID- 15256926
TI  - University of wisconsin solution with trypsin inhibitor pefabloc improves
      survival of viable human and primate impure islets during storage.
AB  - Background. Recent studies suggest that impure islets (islets which have not been
      isolated from exocrine tissue and other parts of the pancreas) have great
      potential for successful transplantation. The evidence that supports this view
      includes findings that embedded islets (islets surrounded by exocrine tissue)
      undergo less apoptosis, peripancreatic lymph nodes prevent recurrence of IDDM
      (insulin dependent diabetes mellitus), and that islet yields and insulin content
      decrease during the purification process. Improved protocols have also been
      developed to prevent allorejection of impure islets. Despite these promising
      results, the storage of impure islets remains difficult, and was a method sought
      to decrease storage losses.Methods. Storage methods of impure human and non-human
      primate islets were compared, using either culture media or University of
      Wisconsin solution (UW). The effects of trypsin inhibition using Pefabloc (Roche
      Molecular Biochemicals, Indianapolis, IN) during storage period were also
      examined.Results. Low temperature and inhibition of trypsin activity during
      storage of impure islets improved both islet yield and viability. It was found
      that using UW solution and trypsin inhibition allowed perfect preservation of
      viable impure islets up to 48 h. A functional assay by glucose stimulation test
      showed these impure islet responded to glucose stimulation after 24 h.Conclusion.
      The benefits of storing impure islets using UW solution and Pefabloc at low
      temperature have been established. This improved method of preserving impure
      islets makes this model of transplantation even more viable.

PMID- 15256927
TI  - Articular Cartilage Chondrocytes are more Advantageous for Generating Hyaline
      like Cartilage than Mesenchymal Cells Isolated from Microfracture Repairs.
AB  - Articular cartilage lacks self-repair capacity. Currently, two methods employing
      autologous cells are used to stimulate repair of articular cartilage. Micro
      fracture induced repair induces autologous mesenchymal cell migration from bone
      marrow. Autologous chondrocytes' transplantation involves in vitro expansion of
      chondrocytes, and later implantation. In 15 patients de-differentiated
      chondrocytes obtained by cartilage biopsy were compared to cells derived from
      repair tissue induced by micro-fracture. These patients all underwent micro
      fracture during the cartilage biopsy procedure. Autologous chondrocytes'
      transplantation was performed at least two months later then the biopsy. Tissue
      bits from articular cartilage and micro-fracture repair tissue were incubated in
      vitro and explant cell cultures established. The cell cultures were assessed by
      immunohistochemistry and induced to differentiate. Differentiation into bone
      tissue was stimulated by addition of basic fibroblast growth factor, ascorbate
      and dexamethasone. High density (micro-mass) culture was used to stimulate
      chondrogenesis. Both cell cultures consist of mesenchymal progenitors as
      indicated by fibroblast growth factor receptor 3 expression and anti-CD-34+
      antibodies. However, the micro-fracture generated repair tissue consists of
      osteocalcin-expressing cells destined to become bone. Collagen type II expression
      does not occur in these cells compared to autologous chondrocytes. Inducible
      nitric oxide synthase expression by microfracture cells is likely to damage
      surrounding articular cartilage in vivo. In conclusion, cells recruited by micro
      fracture are inferior for cartilage regeneration purposes to those from cartilage
      biopsies.

PMID- 15256928
TI  - Preserved Amniotic Membrane Transplantation for Conjunctival Surface
      Reconstruction.
AB  - Objective. To study the efficacy of preserved human amniotic membrane in the
      reconstruction of conjunctival defect created during surgical removal of
      conjunctival lesions or symblepharon lysis.Methods. Preserved human amniotic
      membrane transplantation was performed in 93 eyes of 85 patients for
      reconstruction of various conjunctival surface problems. The indications for
      surgery were (1) pterygium excision (54 eyes), (2) conjunctival tumors excision
      (23 eyes), lysis of symblepharon (13 eyes), and covering a scleral graft (three
      eyes).Results. Success was noted in 69.9% (65/93) eyes, partially success in
      22.6% (21/93) eyes, and failure in 7.5% (7/93) eyes with a mean follow-up of 8.9
      months (1-28 months). In pterygium, conjunctival tumor, symblepharon, and scleral
      graft group, the success rate in each group was 70.3%, 78.3%, 53.8%, and 66.7%
      respectively. No serious immediate post-operative complications or graft
      rejection occurred.Conclusion. Amniotic membrane transplantation can be
      considered an alternative treatment for difficult ocular surface problems, and is
      effective in promoting epithelial healing, and reducing inflammation and
      scarring.

PMID- 15256929
TI  - Hemodilution - an overview of current canadian practices.
AB  - Background. Transplant teams evaluate potential organ and tissue donors to
      exclude donation of tissues at risk for disease transmission. Standards dictate
      that serological tests be performed on every donor to assess the presence of
      transmissible diseases including: Human Immunodeficiency Virus 1 & 2, Human T
      Lymphotropic Virus 1 & 2, Hepatitis C, Hepatitis B surface Antigen, Hepatitis B
      core Antibody and Syphilis. A limitation of serological testing is the risk of
      false negative results due to the dilution of the serum. Hemodilution results
      from the transfusion of fluids (blood products, colloids and/or crystalloid).
      Confidence in the accuracy and sensitivity of donor serology testing is of utmost
      importance to ensure the provision of safe organs and tissues for
      transplantation.Methods. In order to determine the preferred and validated
      methodology for determining hemodilution, if any; and to determine the level of
      hemodilution that jeopardizes serologic test results, we reviewed the literature
      and current testing practices. Tissue banks throughout Canada as well as
      accrediting bodies were contacted regarding the hemodilution algorithm they
      utilize.Results. In the absence of a pretransfusion sample, hemodilution
      calculations are the prevalent methodology for assessing sensitivity of serology
      testing. A literature search and personal communications provided no
      documentation on the validation of any hemodilution algorithm or evidence that
      50% hemodilution is an acceptable level for accurate serology testing.Conclusion.
      A validation of hemodilution algorithms and the acceptable or unacceptable rate
      of hemodilution is required. The utilization of a validated algorithm should be
      mandated in standards to ensure continuity of practice by all transplantation
      centres. If validation cannot be obtained, alternative methodologies for serology
      testing should be investigated.

PMID- 15256930
TI  - Implementation of a Quality Plan (ISO 9002) In a Regional Tissue Bank.
AB  - Quality control and standardized preservation methods are essential in the field
      of transplantation. The International Organization for Standardization (ISO) has
      established a common set of manufacturing, trade and communications standards
      that are applicable worldwide and that provide the basis of a quality plan for
      Tissuebreak Banks.The Sectorial Tissue Banking (STB) of the Regional Blood
      Transfusion Center (RBTC) of Cordoba (Spain) is a non-profit-making tissue bank,
      established in 1992 to provide tissues for surgical procedures to the hospitals
      in a regional area. In 1998, the STB as a part of the RBTC embarked upon the path
      of becoming ISO-certified: after two years of the implementation of the project,
      STB attained ISO 9002 certification, thus becoming one of the first tissue banks
      in Europe to achieve this qualification. In this paper we describe the process of
      becoming ISO-certified, to demonstrate the positive impact that it has had on our
      entire organization.The assistance of an outside consultant who provided the
      necessary information for implementing an ISO quality management system was
      required. The initial improvement was: a well-defined quality manual to address
      all elements of the ISO 9002 standard, an improved document control system,
      detailed standard operating procedures (SOPs) and improved employees training
      processes. A quality committee team and developed quality indicators were
      created. The internal quality auditing program was established by the selection
      of employees from a cross-section of the organization, who were trained in
      internal auditing processes. A formal corrective action system was developed and
      implemented to facilitate process improvement. The consultant conducted a pre
      certification audit, and one month later the certification audit was performed.In
      conclusion, the implementation of an ISO quality program in the STB has helped
      our center to establish a control process in the manufacturing of products and
      services to meet the expectations of our customers, by providing components and
      services that comply with the national regulatory standards and requirements.

PMID- 15256932
TI  - Professor Janusz Komender: European Association of Tissue Banks (EATB) Honorary
      Member for 2000.

PMID- 15256931
TI  - Cadaveric Tissue Supply to the Commercial Sector For Research: Collaboration
      between NHS Pathology and NBS Tissue Services in the U.K., Extending the Options
      for Donors.
AB  - The Peterborough Hospital Human Tissue Bank (PHHTB) and National Blood Service
      Tissue Services (London and South East Zone) (NBSTS) operate within the U.K.
      National Health Service (NHS) and have a system in place to retrieve cadaveric
      tissues for commercial sector research. The collaboration meets the aims of PHHTB
      and NBSTS and is legal, ethical and safe. This paper presents the results of the
      first 20 successful retrievals referred from NBSTS to PHHTB. Cadaveric retrieval
      of tissue for research extends the options for donors and their relatives. The
      research option is particularly welcomed in cases where clinical retrieval for
      tissue transplantation is contraindicated. We believe the system is applicable to
      other centres.

PMID- 15256933
TI  - Letter from the Editor.

PMID- 15256934
TI  - The in vitro growth of human chondrocytes.
AB  - Autologous chondrocyte implantation (ACI) for the treatment of articular
      cartilage defects has been described by other workers, however, relatively few
      details of the in vitro growth of the cells have been published. Here we describe
      the release of cells from adult human articular cartilage and their growth
      characteristics in vitro.Cultures were successfully established from 29 of 30
      biopsies taken from patients aged 20-72 year. No significant relationship was
      found between donor age and initial cell yield following cartilage digest,
      however, the time to primary confluence increased in direct proportion to age.
      Thereafter the kinetics of cell proliferation was independent of donor age.The
      proportion of apoptotic or necrotic cells in the cartilage digest was low and
      increased with time in culture only in those cells which remained non-adherent.
      Conversely, entry into cell cycle was restricted to those cells which had become
      adherent.These results illustrate that previously reported techniques for
      isolating and culturing chondrocytes are reproducible, that adherent chondrocytes
      have considerable proliferative potential, and that concern about cell growth and
      viability need not, in itself, limit the clinical application of ACI to younger
      patients.

PMID- 15256935
TI  - The Influence of Hyperbaric Oxygenation (HBO) on Proliferation and
      Differentiation of Human Keratinocyte Cultures In Vitro.
AB  - A drop in tissue oxygen partial pressure below 30 mm Hg as a result of reduced
      perfusion in an extensive area of acute skin damage, or where a large number of
      chronic skin defects occur, inhibits collagen synthesis and neoangiogenesis in
      the various phases of wound healing. Subsequent granulation and epithelialisation
      are correspondingly impaired.Hyperbaric oxygenation is now recognised as a
      valuable supplementary method of treatment for problematic wounds. Stimulation of
      fibroblast and endothelial cell proliferation through Hyperbaric oxygenation has
      been demonstrated in numerous studies.The aim of this study was to investigate
      the effect of hyperbaric oxygen treatment on the proliferation and
      differentiation of human keratinocyte cultures.The influence of hyperbaric
      oxygenation on the proliferation of human keratinocyte cultures was demonstrated
      using flow-through cytometry and a fluorescence activated cell sorter, which
      detects fluorescence intensity following incorporation of 5-bromo-2'-deoxyuridine
      in cell DNA.The degree of cell differentiation was deduced from the expression of
      various components of the cytoskeleton, such as cytokeratin 10 and involukrin,
      the production of which was quantified through the determination of monoclonal
      antibodies against cytokeratin 10 and involukrin from measurements of
      fluorescence activity in a flow-through cytometer.Hyperbaric oxygenation of cell
      cultures in vitro did not produce a significantly higher rate of cell
      proliferation, so that no increase in vitality was observed.An interesting
      observation following exposure to hyperbaric oxygen was the marked increase in
      expression of both cytokeratin 10 and involukrin, as an indication of accelerated
      cell differentiation.

PMID- 15256936
TI  - Optimization of a method for the cryopreservation of rabbit corneas: attempted
      application to human corneas.
AB  - The purpose of the present study was to set up and test a cryopreservation method
      for long-term storage of human corneas. Therefore the freezing solution was
      optimized in 264 rabbit corneas by testing the type of cryoprotectant, its
      concentration, addition and dilution pattern and exposure temperature. Then
      rabbit corneas were frozen in the optimum solution at different cooling rates and
      thawed in a water bath at different temperatures. Eight human corneas were
      cryopreserved with the method showing optimum results in rabbit corneas and four
      additional corneas were used as controls. Endothelial viability was assessed
      after each step by vital staining and scanning electron microscopy. Best results
      after exposure of rabbit corneas to the freezing solution were achieved when
      using a 10% cryoprotectant concentration, with direct addition/dilution and
      exposure at room temperature (3512 +/-300 viable cells mm(2) when using
      dimethylsulfoxide; 3403 +/- 245 viable cells mm(2) when using 1,2-propanediol).
      Cryopreserved rabbit corneas had the highest endothelial cell survival when
      frozen at 1 degrees C/min and thawed at 37 degrees C (2003 +/- 372 viable
      cells/mm(2) when using dimethylsulfoxide and 1357 +/- 667 viable cells/mm(2) when
      using 1,2-propanediol). Cryopreserved human corneas had 753 +/- 542 viable
      cells/mm(2) when using dimethylsulfoxide and 56 +/- 56 viable cells/mm(2) when
      using 1,2-propanediol. We can conclude that the method developed is easy to
      handle and shows optimum results in rabbit corneas, with an endothelial cell
      survival that is consistent with transplant acceptability criteria. The results
      obtained in human corneas are below prediction and are still unsatisfactory for
      successful use in eye banking.

PMID- 15256937
TI  - Influence of Irradiation on the Risk of Transmission of HIV in Bone Grafts
      Obtained from Appropriately Screened Donors and Followed by Radiation
      Sterilization.
AB  - We studied the effects of radiation (electrons of 6.2 MeV) at different
      temperatures with respect to the inactivation of the human immunodeficiency virus
      to determine the radiosensitivity of the virus. Using a mathematical model
      describing the dependence on radiation dose of the proportion of sterile items in
      a population of bone allografts contaminated by HIV, and subjected to
      irradiation, we have commented on and explained the calculation of the sterility
      assurance level in bone transplantation according to different doses of
      irradiation at different temperatures. Simultaneous application of heat and
      radiation increases inactivation of HIV. Given the relative imprecision of viral
      sensitivity curves and the impossibility of knowing the number of viral particles
      in a patient at a given moment of the disease, irradiation does not authorize
      bone transplantation without screening. However, irradiation can be considered as
      a serious adjuvent to decrease the risk of contamination after screening.

PMID- 15256938
TI  - Bone allograft in revision total knee replacement.
AB  - Revision total knee replacement (TKR) is often associated with the necessity to
      reconstruct a certain amount of bone loss. In a retrospective study we reviewed
      the records of 137 patients who had undergone revision TKR in our department
      between 1990 and 1996, due to loosening or inflection. Bone allografts were used
      in 91 patients (67%) to accomplish stable, new prostheses. Three types of bone
      loss were identified in this group: Type I - minor, Type II - moderate, and Type
      III - large bone defects, located on either side of the knee joint - A, or both
      sides - B.The treatment results of these 91 patients, according to the type of
      bone loss, are presented, showing good functional outcome when utilizing bone
      allografts in revision TKR. However, careful preoperative planning,
      identification of bone loss type, and a well-equipped bone bank are mandatory to
      the success of the operation.

PMID- 15256939
TI  - The banking of arterial allografts in the United kingdom. A technical and
      clinical review.
AB  - The standard graft materials for reconstructive vascular surgery are autologous
      vessels and synthetic prostheses. However, the clinical results are
      unsatisfactory when the diameter of the required graft is less than 6 mm and
      attention has therefore been directed to the possibility of using vascular
      allografts when autologous conduits are not available. In this review, we
      consider the evidence that cryopreserved allogeneic vessels might meet this need.
      Other factors being equal, the literature suggests that arteries will give
      superior performance to veins when grafted into the arterial circulation.
      Conventional cryopreservation techniques have been developed and these can
      provide structurally intact and functional small elastic arteries in animal
      experiments. We conclude that cryopreservation per se produces only modest injury
      which may well be recoverable following grafting. However, both experimental and
      clinical studies suggest that immunological injury is a greater problem.
      Nevertheless, the general indication is that appropriate risk-benefit analysis in
      individual cases will justify the clinical use of cryopreserved allograft
      vessels. Immunosuppression with careful immunological monitoring may be justified
      in the more desperate clinical situations. Finally we conclude that the existing
      tissue bank network in the United Kingdom is well placed to provide surgeons with
      such tissue.

PMID- 15256940
TI  - The Israel National Skin Bank: Quality Assurance and Graft Performance of Stored
      Tissues.
AB  - The Israel National Skin Bank (INSB) was founded jointly by the Israel Defense
      Forces (IDF) Medical Corps and the Ministry of Health in 1986. The prime purpose
      of the Skin Bank is to treat burn victims incurred at war or during mass casualty
      incidences. The INSB Protocol is comprised of international skin bank protocols
      and our previous and present research results. They provide the framework for
      selecting optimal guidelines for procurement, processing, preservation, storage
      and evaluation of transplantation performance of viable skin grafts. For
      evaluation and direct comparison of graft performance of glycerolized or
      cryopreserved skin stored for long periods, we have applied a mouse recipient
      model developed by us. This model assesses graft performance before the rejection
      process takes place. The in vivo design has inherent clinical relevance, which is
      especially appealing. Cryopreserved skin performed better than glycerolized skin
      (p > 0.027), but fresh skin performed significantly better than cryopreserved
      skin (p > 0.003), as analyzed by the Mann-Whitney non-parametric test. Then graft
      performance of skin specimens were cryopreserved by programmed or stepwise
      freezing and stored at -80 degrees C or in liquid nitrogen for 1 and 6-10 months
      was evaluated. The average score of skin preserved by programmed freezing and
      stored in liquid nitrogen is the highest for both storage periods. This method
      has a highly significant advantage (p < 0.007) over the others for 6-10 months
      storage, evaluated by graft adherence. Several interaction factors determine the
      quality of cryopreserved skin. Highly significant is the interaction
      factor/'combined effect' of sample variability with the method of
      cryopreservation or with the storage period. Finally, the results of paired
      comparison of selected histology criteria of cryopreserved to fresh skin
      indicated that storage of skin for up to 5 years did not impair significantly its
      performance compared to fresh skin, whereas, after six years of storage, there
      was a highly significant (p < 0.001) impairment in skin quality. We offer a
      simplified in vivo model and analysis for cryopreserved skin graft performance,
      suggesting that the evaluation procedures, which are issues of great interest in
      skin banking, may help future skin banks to make informed choices and decisions
      regarding quality issues.

PMID- 15256941
TI  - The Analysis of Bacterial Results in the Kidney Perfusion Fluid and Bone
      Allografts in Human Multiorgan Donors.
AB  - In 19 young human multiorgan donors, we simultaneously analyzed the bacterial
      contamination of the kidney perfusion fluid and all retrieved bone allografts.
      Donor exclusion criteria were done according to the American and European
      Association of Tissue Banks excluding all patients with perforating wounds. The
      kidney perfusate revealed a contamination in 17 of 19 (89.5%) donors. Allograft
      testing demonstrated positive bacterial growth in 34 of 76 allografts (44.7%).
      Microorganisms originated from the normal skin flora and could be related to
      contamination during the harvesting procedure. In 5 cases we cultured identical
      bacterial subspecies in both cultures as a possible sign for systemic bacterial
      spreading during the multiorgan harvesting procedure.

PMID- 15256942
TI  - Artificial cornea and the future of eye banking.
AB  - A report on the construction of functional human corneal equivalent reflects a
      step towards creation of an artificial cornea. We discuss the current status of
      supply and demand for corneas for transplanation, and wonder if the creation of
      an artificial cornea will have an effect on corneal transplantation in the near
      future

PMID- 15256943
TI  - Editorial.

PMID- 15256944
TI  - Quality issues in tissue banking: quality management systems - a review.
AB  - The situation in tissue banking changed radically and fundamentally at the
      beginning of the 1990s. The essential causes are on the one hand, the continually
      increasing demand for human cells and tissue and other biological material for
      clinical use and research, and on the other hand, the rapid progress in the
      medical, technical and natural sciences. Biotechnology in particular, has
      profited from this. Modern tissue banks could no longer be imagined without its
      methods.A consequence of these developments and a prerequisite for the fulfilment
      of the derived requirements is the necessity for national and international
      cooperation as well as the harmonisation of ethical principles and quality
      assurance standards and regulations (von Versen (1999) Ann Chir Gynaecol 88: 215
      220). The introduction of an all-encompassing Quality Management System (QMS) is
      a suitable instrument for this purpose.After the presentation of explanations and
      definitions of quality terminology, this article describes the use of the
      international standard ISO 9000 as a general QMS, which embraces both the
      specific methodology as well as the general aspects of Quality Management
      (research and development, design control, education and training, documentation,
      traceability, management control, corrective action, etc.) in tissue banking. The
      individual elements of this system are explained and selected examples are
      described. The authors look upon this QMS as an indispensable instrument for
      harmonisation and international cooperation in tissue banking.Finally, the use of
      such a standard would be a positive sign to the regulatory authorities and the
      public that tissue banking is making a visible effort to introduce a world-class
      QMS in its operations.

PMID- 15256945
TI  - Processing of whole femoral head allografts: a method for improving clinical
      efficacy and safety.
AB  - Femoral heads removed during primary hip replacement surgery are widely utilised
      as a source of allograft bone. Despite evidence that processing these grafts to
      remove blood and marrow elements improves both the clinical performance and
      safety of these allografts, many are transplanted without any processing being
      applied at all. The goal of this study was to investigate the efficiency of an
      allograft processing protocol which incorporates pasteurisation, (3 h, 56-60
      degrees C) centrifugation, (1850g, 2 x 15 min, 40 degrees C) sonication, and
      repeated washing in warm (56-60 degrees C, 19 h) distilled, sterile water to
      remove blood and marrow elements from the graft. The protocol also involves
      applying heat treatment to the grafts which has been demonstrated to inactivate
      many pathogenic viruses. Following the processing procedure, the grafts are
      lyophilised and sterilised with ethylene oxide gas. The amount and rate of
      removal of 4 different components of blood and marrow from 6 whole femoral head
      allografts were measured. These were lipid, soluble protein, elastase and
      chloride ions. Lipid removal was assessed gravimetrically by solvent extraction
      of dried samples, soluble protein by the Bradford assay, elastase by
      radioimmunoassay and choride ion content by a modified commercially available
      colorimetric assay. Removing lipid from grafts has been shown to increase the
      rate of incorporation when the graft is used clinically. Elastase was studied as
      a marker of leukocyte removal, as evidence suggests the majority of potentially
      infective transmissible spongiform encephalopathy (TSE) activity resides in a sub
      population of leukocytes. Soluble protein was studied as a marker of plasma
      removal, as a smaller amount of TSE infectivity resides here. Chloride removal
      was measured as this is a necessary pre-requisite to terminal sterilisation with
      ethylene oxide. The results showed that the protocol removed 74.5% (range: 68.0
      90.8) of the lipid content, 96.4% (range: 94.8-98.4) of the soluble protein
      content, 97.7% (range: 97.1-100) of the elastase content and 98.8% (range: 98.0
      99.2) of the chloride ion content. We have shown that processing designed to
      improve the clinical efficiency and safety of bone allografts can be accomplished
      without compromising the structural and biological properties of the graft.

PMID- 15256946
TI  - Biomechanical Strength of Large Diaphyseal Deep-frozen Allografts.
AB  - The aim of this paper is to study the biomechanical strength of deep-frozen
      allografts as they heal. Twenty-eight adult cats were used with the tibia as the
      experimental model site. Deep-frozen allografts stored at -80 degrees C were used
      to reconstruct a large tibial defect (at least two-thirds of the diaphysis). An
      intra-medullary rod was used for fixation. The healing was studied by X-ray at
      observation periods of 4, 6, 8, 12, 16, 24 and 36 weeks. Post-transplantation
      biomechanical testing was performed using the Shimadzu Universal Testing Machine
      DCS series with a torsion test device of 50 kg force metre. Parameters studied
      included maximum torque, torsional stiffness and energy of absorption. The
      transplanted grafts were compared to the mechanical properties of the internal
      controls of the normal opposite tibia of each cat. The results of the mechanical
      tests demonstrated that deep-frozen allografts did not regain normal strength. At
      nine months, only about 60% of normal torque strength and about 80% of normal
      torsional stiffness was achieved. Clinically, it is important to employ strong
      and rigid internal fixation using intra-medullary nailing rather than plating to
      allow for immediate mobilisation and reduce the rate of graft fracture.

PMID- 15256947
TI  - Chondrocyte transplantation for osteochondral defects with the use of suspension
      culture.
AB  - Cartilage graft is considered to be useful in repairing chondral or osteochondral
      defects. One method of the cartilage graft is achieved by autologous chondrocyte
      transplantation following cell culture. However, chondrocytes change their
      phenotype during culture. We used costal chondrocytes cultured over agarose
      (suspension culture) as a source of graft materials. The suspension-cultured
      chondrocytes formed aggregate in culture. We first examined the expressions of
      cartilage-specific matrices of cultured chondrocytes after two weeks in culture.
      The chondrocytes cultured over agarose expressed more type II collagen mRNA than
      those cultured on plastic dishes did after two weeks in culture. Safranin O
      staining showed the presence of glycosaminoglycans in the chondrocyte culture
      over agarose, while glycosaminoglycans were not observed in the culture on
      plastic dishes. We then examined the changes of rat articular osteochondral
      defects after transplantation of suspension-cultured chondrocytes. The aggregate
      of suspension-cultured chondrocytes was easily picked up with forceps and
      transplanted in the osteochondral defects. The defects were filled with safranin
      O-stained hyaline cartilage tissue two weeks after chondrocyte transplantation.
      On the contrary, the fibrous materials, which were not stained with safranin O,
      were observed in the control defects. These results suggest that the suspension
      cultured chondrocytes are useful for autologous cartilage grafts by preserving
      chondrocyte phenotype.

PMID- 15256948
TI  - Application of Preserved Human Amniotic Membrane for Corneal Surface
      Reconstruction.
AB  - Objective: To evaluate the efficacy of preserved human amniotic membrane
      transplantation for reconstruction of the corneal surface diseases.Methods:
      Preserved human amniotic membrane transplantations were performed in 84 eyes of
      78 patients for corneal surface reconstruction. The indications were limbal stem
      cell deficiency from Steven-Johnson syndrome, chemical burn and herpes keratitis
      (27 eyes), bullous keratopathy (26 eyes), persistent epithelial defect and dellen
      (17 eyes), band keratopathy (11 eyes), preparing for prosthesis (1 eye), corneal
      ulcer (1 eye) and acute chemical burn (1 eye).Results: Success was noted in 83.3%
      (70/84) eyes, partial success in 13.1% (11/84) eyes, and failure in 3.6% (3/84)
      eyes for an average follow-up of 10.5 months (3 - 29 months). No patient
      developed major immediate post-operative complications.Conclusion: Amniotic
      membrane transplantation can reduce inflammation, promote corneal epithelial
      healing, and decrease irritation in corneal surface problems.

PMID- 15256949
TI  - Versatile Utilization of Massive Bone Allografts in Orthopedic Surgery.
AB  - The clinical use of massive bone allografts in orthopaedic surgery has become
      common practice in tumour operations and primary and revision total joint
      replacement. In certain special clinical situations associated with large bone
      loss, such as trauma, limb-length discrepancy repair or even infection, massive
      bone allografts can be successfully used. We present our treatment results of 47
      patients who suffered from major bone loss due either to trauma, limb-length
      discrepancy repair, or infection. Our results (> 2 years minimum follow-up to
      allow full-bone allograft incorporation) indicate that the use of massive bone
      allografts in these special and delicate medical conditions is feasible, and have
      good functional results.

PMID- 15256950
TI  - Bangkok biomaterial center: 15 years experience in tissue banking.
AB  - Tissue banking is started in Thailand in 1979 at the Department of Orthopaedic
      Surgery, Siriraj Hospital, Bangkok. At that time tissues produced were freeze
      dried bone allografts which were sterilized by ethylene oxide. In 1984, the
      freeze-dried tissue allograft project received an award from the National
      Research Council of Thailand. The Bangkok Biomaterial Center was officially
      inaugurated on December 6, 1984 under the Royal Patronage of H.R.H. Princess
      Galyanivadhana and is located inside the Siriraj Hospital. The Center is involved
      in the procurement, processing, storage and development of bone and tissue
      allografts. A variety of allografts including bone, cartilage, fascia lata, dura
      mater, cornea and also cardiovascular tissues have been procured and processed.
      Preservation and long-term storage are accomplished by freeze drying and deep
      freezing. Grafts prepared by the Center are supplied free of charge at the
      request of surgeons in hospitals throughout Thailand and in neighboring
      countries. The Center acts as the National Tissue and Allograft Bank of Thailand.
      From December 1984 to February 2000, the Center has processed a total of 20 524
      allografts: 16 981 freeze-dried bones, 705 deep-frozen bones, 1838 freeze-dried
      amnion, 559 freeze-dried dura mater, 342 freeze-dried fascia lata, 46 costal
      cartilage, 18 corneas, 2 skin, 5 trachea, 22 fresh tendon and 6 bone substitutes.
      The allografts processed were used in 2049 patients by 223 surgeons in 53
      hospitals in Thailand and 4 cases in neighboring countries. There have been 413
      cadaveric donors, 619 living donors, 16 brain dead donors and 270 graveyard
      donors. There have been complications in 126 patients (6.14%) due to various
      clinical conditions. There have been production and application of 4
      hydroxyapatite occular implant by the Center. The Center is in the process of
      establishing a full-fledged Research, Clinical and Cell Culture Laboratory.

PMID- 15256951
TI  - European association of tissue banks standards for cryopreserved cardiovascular
      tissue banking.
AB  - The Cardiovascular Tissue Banking Standards are designed as an addition to the
      General Standards of the European Association of Tissue Banks to provide a
      minimum acceptable level for the donation, processing, storage, testing,
      labelling and distribution of cardiac tissue throughout Europe. The aim is that
      all heart valve banks in Europe should work to these Standards so that heart
      valves can be exchanged between countries without having to check the individual
      protocols of the donor processing facility. The writing of the Standards has been
      performed by the Heart Valve Council of EATB with input from cardiac surgeons. It
      is proposed that once the Standards are accepted they will form the document on
      which EATB may accredit tissue banks in the future and may form the basis on
      which National Legislation for Tissue Banking is based.

PMID- 15256953
TI  - Co-editorial.

PMID- 15256952
TI  - Letter from the Editor.

PMID- 15256954
TI  - Bone allografts: past, present and future.
AB  - Bone allograft transplantation has been performed in humans for more than one
      hundred and twenty years. During the first one hundred years (1880-1980), the
      major problem in bone allograft transplantation was availability. Most of the
      bone grafts used during this time were autografts. Allografts were not available
      due to a lack of legislation protecting procurers and processers. In addition,
      surgical procedures requiring allografts were not being performed. During the
      next twenty years (1980-2000), as allografis began to be used, the major issue
      was safety. Diseases transmitted during this period included AIDS and hepatitis.
      Avoidance of disease transmission became paramount. Sensitive blood tests and
      extensive efforts by bone banks to develop ways to clean. bone and clear it of
      infectious agents helped provide safe transplants. With concerns of availability
      and safety receding, the major issue in the future (2000-? ) will be the efficacy
      of the transplant. How allograft bone remodels in the host, how it incorporates
      and heals to host bone and how it integrates with the host skeleton will be the
      most important concerns of bone bankers and tissue transplant surgeons. Future
      research efforts will be applied to bone allograft transplantation to ensure that
      bone transplants heal quickly and sufficiently to be able to function as part of
      the weight-bearing skeletal system.

PMID- 15256955
TI  - Analysis of potential causes of positive microbiological cultures in tissue
      donors.
AB  - The purpose of this statistical analysis is to determine what factors are the
      major contributors to bacterial contamination of recovered human cadaveric
      tissue. In this study we analyzed factors that could contribute to an increased
      bacterial bioburden from recovered tissues using the following independent
      variables: (1) the physical recovery environment; (2) recovery before or after an
      autopsy; (3) the length of time from death to recovery; (4) the cause of death;
      (5) the length of time to complete recovery; (6) the number of staff involved
      with the tissue recovery; and (7) the impact of organ and skin recovery on
      musculoskeletal contamination rates.In these analyses we used analysis of
      variance of main effects on data from seven tissue banks. The scale of the
      analysis included 1036 donors each having multiple cultures to better control for
      the inherent large variation in this type of data. We looked at several dependent
      variables. The dependent variable that was most useful was 'percent positive
      cultures'.The results of the combined data differed from analyzing the tissue
      banks individually. The differences in each tissue bank's procedures and
      techniques were responsible for most of the variability. Depending on how the
      data was organized, statistically significant increases in bioburden were seen
      with: (1) recoveries after autopsy; (2) location of the recovery; (3) length of
      time taken for a recovery; (4) size of the recovery team; and (5) the impact of
      organ and skin recovery on musculoskeletal contamination rates.In conclusion,
      statistical analysis of recovery cultures can be a powerful tool that may be used
      to indicate problems within any bank's recovery procedures or techniques.

PMID- 15256957
TI  - Hemodilution due to blood loss and transfusion and reliability of cadaver tissue
      donor infectious disease testing.

PMID- 15256956
TI  - The procurement team as a factor of bone allograft contamination.
AB  - We studied the effect of the procurement team on the risk of contamination in 270
      large bone allografts retrieved from 53 non-living donors under strictly aseptic
      conditions.The overall contamination rate was 8.1%. When the procurement team was
      constituted by three or less members the contamination rate was 5.6%, while if
      there were four or more members the rate was 12.9%; this difference was
      significant in the statistical analysis.We conclude that a procurement team
      constituted by three or less trained members is a determinant factor in
      decreasing the bacterial contamination rate of bone allografts.

PMID- 15256958
TI  - Methanol Intoxication Victims are Suitable Donors for Corneal Transplantation.
AB  - Purpose. To evaluate the outcome of corneal transplantation and the feasibility
      of tissue donation from donors with methanol intoxication.Methods. Four corneas
      from two methanol intoxication victims were procured and transplanted in four
      patients at our medical center. The outcome and graft survival were
      evaluated.Results. The recipients were between 12 and 49 years of age.
      Indications for transplantation were keratoconus (two patients), post-traumatic
      corneal perforation (one patient) and alkaline burn (one patient). The follow-up
      period ranged between 12 and 60 months. All grafts remained clear, and the
      postoperative visual acuity was 20/30 in keratoconus patients and 20/60 in
      others.Conclusions. The methanol intoxication victims appear to be suitable
      donors for corneal transplantation. To the best of our knowledge, this is the
      first study to report successful corneal transplantation from donors with
      methanol intoxication.

PMID- 15256959
TI  - Hidden effects of cryopreservation on quality of human spermatozoa.
AB  - The effects of cryopreservation on two characteristics of human spermatozoa were
      investigated: the early phases of disturbed plasma membrane function and the
      activity of enzymes in intact spermatozoa. The membrane function was detected by
      means of the calcium-dependent binding of fluorescein isothiocyanate (FITC)
      conjugated Annexin V to sperm plasma membranes. Annexin V monitors the
      translocation of phosphatidylserine from the inner to the outer leaflet of the
      plasma membrane, which is one of the earliest features of membrane
      disintegration. For the second aim synthetic fluorogenic substrates for
      peptidases, proteinases, esterases, elastases and collagenases were applied.
      These substrates, CellProbe trade mark reagents consist of different peptide
      sequences, specific for the enzymes, and a fluorescein- or rhodamine 110-dye
      moiety. They enter the cells without previous membrane permeabilisation and
      exhibit fluorescence after cleavage depending on enzyme activity. The number of
      positive cells and the intensity of the fluorescence were determined by flow
      cytometric analysis comparing fresh spermatozoa with cryopreserved ones. Thirty
      five semen samples collected from 35 donors were cryopreserved using the freezing
      medium TEST yolk buffer. All specimens showed normal spermiogram parameters.
      Twenty-five of the samples were used for detection of Annexin V-FITC binding and
      10 semen samples for investigations of the intracellular enzymes. The Annexin V
      assay applied two fluorescent dyes (Annexin V, AN and propidium iodide, PI) which
      led to three groups of spermatozoa (a) viable spermatozoa (AN V-negative and PI
      negative), (b) dead spermatozoa (AN V-positive and PI-positive) and (c) cells
      with impaired but integer plasma membrane (AN V-positive and PI-negative). The
      percentage of vital Annexin V-negative spermatozoa (x +/- SEM) decreased
      significantly (p < 0.001) from fresh spermatozoa (51.6 +/- 3.1) to cryopreserved
      spermatozoa (26.6 +/- 2.2%) and was associated with their motility (57.9 +/- 1.9%
      motile fresh spermatozoa vs. 22.6 +/- 3.9% motile sperm after cryopreservation).
      Of the spermatozoa 28.2% were Annexin V-positive before and 44.4% after
      cryostorage even though they did not bind to PI. Thus, vital spermatozoa showed a
      disturbed membrane function indicating viability before as well as after
      cryostorage. Moreover, after cryopreservation the spermatozoal fluorescence
      increased applying substrates for butyryl esterase (p < 0.05), prolyl
      aminopeptidase (p < 0.001) and val-lys-(VK)-cathepsin (p < 0.001). In contrast,
      the activities of fluorescein diacetate (FDA)- and FDA/sodium fluoride (NAF)
      esterase (p < 0.05), ala-ala-pro-val-(AAPV)-elastase (p < 0.001), gly-pro-leu-gly
      pro-(GPLGP)-collagenase (p < 0.05) and gly-gly-leu-(GGL)-subtilisin (p < 0.001)
      decreased after cryopreservation. The substrates for arg-gly-glut-ser-(RGES)
      elastase, gly-phenyl-gly-ala-(GFGA)-collagenase and threo-pro-(TP)-cathepsin were
      not cleaved before as well as after cryostorage. In addition to the known effects
      of sperm cryopreservation our results showed two further alterations of human
      ejaculated spermatozoa: (a) disturbed plasma membrane function, which is not
      detectable by supravital staining and (b) a changed pattern of intracellular
      enzyme activities.

PMID- 15256960
TI  - Validation of radiation sterilization dose for lyophilized amnion and bone
      grafts.
AB  - A limited number of grafts produced in one batch is the main constrain to
      validate radiation sterilization dose of amnion and bone grafts according to ISO
      standard. The validation experiments done were according to ISO 13409 with a
      slight modification in sampling method. The experiments were carried out three
      times by using 20 samples each, 10 for bio-burden enumeration and 10 for
      sterility test at verification dose. The average bio-burden with sample item
      portion (SIP) = 1 for amnion membranes were 98, 50 and 69 cfu respectively and 0
      cfu for bone grafts. Verification dose experiments, were done at doses of 2.90
      kGy for bone grafts and 5.13 kGy for amnion grafts and the results of sterility
      tests showed that amnion grafts got one positive and bone grafts got 0 positive.
      The results met the requirements of ISO 13409 so that the radiation sterilization
      dose, at sterility assurance level of 10(-6) was 25 kGy for both amnion and bone
      grafts. Viral contamination was excluded in this experiment.

PMID- 15256961
TI  - Proposed Donor Screening Questionnaire.

PMID- 15256962
TI  - The evolution of quality systems in human bone banking: the u.s. Experience.
AB  - This paper illustrates the evolutionary changes that have taken place in human
      bone banking in the United States since the 1970s to the present, with an
      emphasis on quality control systems. Specific examples of quality controls are
      outlined, along with their intended purposes. Particular importance is placed on
      the gradual change in emphasis from bacteriological concerns to viral concerns
      and quality control systems.

PMID- 15256963
TI  - Letter from the Editor.

PMID- 15256964
TI  - American association of tissue banks: a historical reflection upon entering the
      21st century.
AB  - The American Association of Tissue Banks (AATB) is a scientific, not-for-profit,
      peer-group organization founded in 1976 to facilitate the provision of
      transplantable tissues of uniform high quality in quantities sufficient to meet
      national needs. The Association was created well before there was governmental
      oversight of tissue banking. The organization consists of individuals involved in
      tissue banking, medical users, and scientists in the field. Current structure
      consists of a 13-member Board of Governors with specific subgroups including
      Musculoskeletal, Reproductive, Skin, Tissue Bank Councils and Council of
      Accredited Tissue Banks. A historical review shows the evolution from development
      of guidelines to publication of standards, and from an inspection conducted by
      peers to one conducted by an independent, trained professional inspector.
      Association growth and historical accomplishments are highlighted.

PMID- 15256965
TI  - The US Navy Tissue Bank: 50 Years on the Cutting Edge.
AB  - The US Navy Tissue Bank was established in 1949 by Dr. George Hyatt, an
      orthopaedic surgeon at the Naval Medical Center in Bethesda, Maryland. The Navy
      program was the first of its kind in the world and established many of the
      standards that are followed today. During the 1950s, the identification of
      appropriate donor criteria for tissue donation, the development of procurement
      and processing methods, the establishment of a graph registry and documentation
      and the clinical evaluation of a variety of tissues were pioneered at this
      facility. Cryopreservation, freeze-drying, irradiation sterilization of tissue,
      as well as immunological principles of tissue transplantation, were developed
      during the 50 years of research and development by Navy scientists. Organ
      preservation, cadaveric bone marrow recovery and immunosuppressive protocols were
      also developed at the Navy Tissue Bank. The Navy was also instrumental in the
      establishment of the National Marrow Donor Program and the American Association
      of Tissue Banks in the US.Although the Navy Tissue Bank has ceased activity after
      50 years of excellence, it should be recognized as the first standard setter for
      the world community of tissue banks.

PMID- 15256966
TI  - Brief history of the tissue bank, charles university hospital, hradec kralove,
      czech republic.
AB  - A brief history of the Tissue Bank (TB) of the University Hospital Hradec
      Kralove, Czech Republic, established by Dr. R. Klen in 1952 is presented. In Dr.
      Klen's original concept the TB was defined as a department specialised in the
      harvesting, processing, preservation, storage and distribution of various kinds
      of tissue for clinical and experimental practice. The first kinds of tissue
      collected in cadaveric donors were corneas, bone and skin. Xenogeneic cartilage
      and bone grafts were prepared at the same time. Later, preparation of soft
      connective tissues and chorion-amnion was introduced. During the first 15 years
      of activity a total of 11,443 grafts preserved by hypothermy at +4 degrees C or
      freezing in absence of cryoprotectants (-20 degrees C) were prepared. In the 60's
      freeze-drying of tissue grafts was introduced and the bank of cryopreserved cell
      lines was established. In the 80's cryopreservation of haematopoietic progenitor
      cells for clinical transplantations was started and the spectrum of tissue grafts
      was enlarged (xenogeneic pericardium and allogeneic specially treated dura mater
      for neurosurgical operations, pigskin for burn treatment, demineralised bone for
      parodontology and implantology). In the 90's human keratinocyte culture for
      treatment of burns and chronic skin defects was started. The human milk bank and
      organ bank co-operating with the Regional Transplantation Centre are component
      parts of the TB as well. The TB is an institutional member of the European
      Association of Tissue Banks and annually delivers approximately 1000 grafts that
      are used in University and county hospitals as well as in surgeons' private
      practices. Health insurance companies reimburse all grafts on a non-profit and
      tax-free basis.

PMID- 15256967
TI  - Fetal tissue banking for transplantation: characteristics of the donor population
      and considerations for donor and tissue screening.
AB  - We initiated this study to evaluate the suitability for therapeutic use in
      transplantation of tissues obtained from human abortuses. We have developed
      protocols for the collection, handling and preservation of hepatic stem cells
      from electively aborted embryos and have developed methods for assessment of the
      cells so derived and processed. In this paper we present our findings regarding
      screening of potential donors, acquisition of fetal tissues, and assessment of
      the tissues for potentially infectious contaminants. We assess the suitability of
      the tissue donors according to current standards used for donors of commonly
      transplanted tissues (e.g., bone grafts, skin grafts and heart valves) and
      present data regarding the real availability of tissues from elective abortion
      procedures that would meet those standard tissue banking criteria.We specifically
      evaluated the donor's willingness to provide a blood sample for testing,
      conducted a detailed interview similar to those used for typical organ and tissue
      donors, and assessed the type and incidence of contamination in collected
      tissues. We find that although many women are willing to consent to use of the
      tissues for transplantation, attrition from the study for various reasons results
      in few fetal organs ultimately realistically available for transplantation.
      Typical reasons for attrition include: unwillingness to have a blood sample drawn
      or tested, positive serology results, social/medical high risk factors for
      acquisition of transmissible disease, no identifiable organs available, and
      unacceptable microbial contamination. Thus, although it might seem that due to
      the numbers of abortions performed annually, that there would be substantial
      numbers of suitable tissues available, only a small proportion are truly suitable
      for transplantation.

PMID- 15256968
TI  - Investigation of functional and morphological integrity of freshly isolated and
      cryopreserved human hepatocytes.
AB  - There is a pressing need for alternative therapeutic methods effective in the
      treatment of patients with liver insufficiency. Isolated human hepatocytes may be
      a viable alternative or adjunct to orthotopic liver transplantation in such
      patients. The purpose of this study was to evaluate the viability and functional
      integrity of freshly isolated and cryopreserved human hepatocytes, in preparation
      for a multi-center human hepatocyte transplantation trial. We are currently
      processing transplant-grade human parenchymal liver cells from nondiseased human
      livers that are obtained through a network of organ procurement organizations
      (OPOs). Thus far, sixteen hepatocyte transplants have been performed using
      hepatocytes processed by our methods. At the time of referral all specimens were
      deemed unsuitable for transplantation due to anatomical anomalies, high fat
      content, medical history, etc. Hepatocytes were isolated from encapsulated liver
      sections by a modified two-step perfusion technique. Isolated cells were
      cryopreserved and stored in liquid nitrogen for one to twelve months. The total
      yield of freshly isolated hepatocytes averaged 3.7x10(7) cells per gram of wet
      tissue. Based on trypan blue exclusion, fresh preparations contained an average
      of 85% viable hepatocytes vs. 70% in cryopreserved samples. The plating
      efficiencies of cells seeded immediately after isolation ranged from 87% to 98%,
      while those of cryopreserved/thawed cells were markedly lower. Flow cytometry
      analysis of cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl
      ester (CFSE) showed that there was no significant difference in viability
      compared with trypan blue staining. Both freshly isolated hepatocytes and those
      recovered from cryopreservation showed typical and intact morphology as
      demonstrated by light and electron microscopy. The product of the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reaction was always
      expressed more intensely in cultures of freshly isolated hepatocytes.
      Measurements of lactate dehydrogenase (LDH) leakage were inversely correlated
      with trypan blue exclusion and CFSE labeling. Energy status, evaluated by the
      intracellular ATP concentration measurements, and various liver-specific
      functions such as urea synthesis and metabolism of 7-ethoxycoumarin were
      maintained both in fresh and cryopreserved/thawed hepatocytes. However, the
      activities were expressed at different levels in thawed cells. These data
      illustrate the importance and feasibility of human hepatocyte banking. In
      addition, it is clear that further refinements in the methods of hepatocyte
      isolation and cryopreservation are needed to utilize more fully these valuable
      cells in the clinic.

PMID- 15256969
TI  - The effects of prolonged cryopreservation on the biomechanical properties of bone
      allografts: a microbiological, histological and mechanical study.
AB  - Bone allografting is the most common form of allotransplantation in modern
      medicine. Bone banking is usually the major part of most tissue banks throughout
      the world. Several years ago, many standards of bone banking were set
      empirically, and have never been evaluated. One particular parameter or standard
      was outdating graft materials after 5 years of storage. This study was conducted
      to evaluate the effect of prolonged cryopreservation on the biomechanical
      properties of bone allografts and establish whether graft materials become
      contaminated during long-term storage.Proximal humeral bone allografts were
      obtained from the bone bank after 1, 3 and 5 years of -80 degrees C
      cryopreservation. Samples of each humeral head, i.e., cartilage, subchondral bone
      and spongy bone were histologically examined for inter- and intra-cellular
      changes. A three-point mechanical bending test was used on identical pieces of
      cortical bone to compare fresh and cryopreserved materials. Fresh-retrieved
      cortical bone using identically-sized segments, served as a control. Cultures
      were taken from each respective sample to determine contamination or
      sterility.Results of both the histological and mechanical testing showed that
      there were no significant, qualitative histological, or quantitative mechanical
      differences among the samples. All the cultures were negative. Therefore, based
      on this study's parameters, bone allografts can safely be used after a
      cryopreservation period of over 5 years and should not be discarded.

PMID- 15256970
TI  - Biocompatibility Studies of a New Biosynthetic Dermal Substitute Based on
      Collagen/Hyaluronan Conjugate.
AB  - The use of glycosaminoglycans (GAGs) as the second macromolecular component with
      collagen for the membrane preparation is based on the idea to create a
      biodegradable scaffold for new tissue. A hybrid collagen/hyaluronan membrane with
      specific bubble macrostructure was designed to serve as a synthetic dermal
      substitute. The objectives were to explain the two questions: what is the local
      biological response to the implanted membrane, and what is its reconstruction
      rate in tissue. The histological study proved low irritability, good
      compatibility, ingrowth of autologous tissue starting on day 7 post implantation,
      and resorption within four weeks. The major part of the implant was replaced by
      autologous tissue at the end of three weeks post implantation. The overall local
      biological response to implant was very good.

PMID- 15256971
TI  - The incidence of hepatitis C virus positive serological test results among cornea
      donors.
AB  - Purpose. We have noticed that the incidence of positive serological tests of
      hepatitis C virus (HCV) among cornea donors in our eye bank is higher than
      expected. The purpose of this study was to determine the incidence of these
      positive findings and identify the contributory risk factors.Methods. All corneas
      procured between June 1993 and June 1997 were included in this retrospective
      study. In all cases a routine work-up, including serological testing of donors'
      sera and evaluation of the procured corneas, was performed prior to corneal
      transplantation. Donors found to be positive for HCV antibodies were compared to
      our general population of corneal donors, with respect to the demographic,
      serological and ophthalmological data obtained during the transplantation work
      up.Results. All 851 corneas procured from 438 donors were included. Antibodies to
      HCV were found in 29 donors (6.6%). Following positive test results, 57 corneas
      (6.7%) were discarded. The time from donors' death to cornea procurement was
      significantly longer among HCV-positive patients than in the general donor
      population (12.3 vs. 9.3 h, p<0.0003). No other differences were detected between
      the two groups.Conclusion. Delay in harvesting of donated corneas may give rise
      to false positive HCV-antibodies test results, which may be partially responsible
      for the high rate of positive findings among cornea donors, with consequent
      tissue wastage.

PMID- 15256972
TI  - Ectopic liver and hepatocarcinogenesis.
AB  - Hepatocellular carcinomata are relatively rare in the western hemisphere, but
      they are much more common in South-East Asia and sub-Saharan Africa due to high
      endogenous levels of hepatitis B and C. Ectopic liver tissue usually is found
      incidentally (frequently at cholecystectomy), but it may also be found due to
      neoplastic changes or compressive effects. Ectopic liver tissue has an increased
      neoplastic potential over orthotopic liver, which we postulate is due to
      compromised vascular supply and biliary drainage. These lesions may be
      susceptible to surgical resection, although long-term follow-up data are poor.
      Ectopic or accessory liver tissue is a rare condition. Most commonly, it is found
      incidentally, but it may also be found as a result of neoplasia or compressive
      effects. These lesions appear to have an increased potential for the development
      of hepatocellular carcinoma in the absence of malignancy in the mother liver. Due
      to their anatomical features, these carcinomata appear to be susceptible to
      curative resection, although long-term follow-up data are poor. These carcinomata
      have been reported more frequently from South-East Asia than from Western
      countries; however, the common risk factors for hepatocellular carcinoma, such as
      infection with hepatitis B or C and cirrhosis, appear to be less implicated than
      in carcinomata of the orthotopic liver. In ectopic or accessory liver tissue,
      development of hepatocellular carcinoma may be the result of compromised vascular
      supply or biliary drainage.

PMID- 15256973
TI  - Ectopic liver and hepatocarcinogenesis: report of three cases with four years'
      follow-up.
AB  - Hepatocellular carcinoma (HCC) may arise in ectopic livers, which are autonomous
      islands of normal liver parenchyma located in the abdomen or thorax. The majority
      of HCCs in ectopic livers are reported in oriental patients. We describe here
      three new cases of HCC in Caucasian patients. The clinical presentation varied
      from dull epigastric pain in one patient, to abrupt onset with signs and symptoms
      of acute abdomen caused by intra-abdominal bleeding in another patient, to an
      unexplained progressive increase of alpha-fetoprotein serum levels in a third
      patient. None had risk factors for HCC or liver disease. One of the patients
      developed HCC at age 34 years; she is the youngest patient ever described to
      develop HCC in ectopic liver. Our data further strengthen the hypothesis that
      ectopic livers are particularly predisposed to developing HCC. The patients were
      followed up for 4 years after surgery: two remain free of disease, suggesting
      that the unique localisation and growth pattern may render these tumours
      particularly susceptible to curative resection.

PMID- 15256974
TI  - Liver abscess complicating transcatheter arterial embolization: a rare but
      serious complication. A retrospective study after 3878 procedures.
AB  - OBJECTIVES: Liver abscess is one of the complications of transcatheter arterial
      embolization (TAE) for hepatocellular carcinoma. We studied the clinical features
      and analysed the incidence, risk factors, helpful clinical clues, culture
      profiles and predictive factors of post-TAE liver abscess. The influence of
      abscess development on the evolution of the tumour process was also studied.
      METHODS: We retrospectively reviewed records of 3878 TAE procedures performed
      over a 6 year period. RESULTS: Ten cases of liver abscess developed in nine
      patients (eight males and one female). The incidence was 0.26% (10 episodes/3878
      procedures). The main clinical presentations included fever (91.7%), chills (50%)
      and abdominal pain (33.3%). All but one febrile patient presented fever in a
      recurrent form. The positive culture rates were 41.7% for blood and 83.3% for
      pus. Gram negative bacteria were found in 80% of blood cultures and 68% of pus
      cultures. Polymicrobial infections were encountered in 60% of the blood cultures
      and 70% of pus cultures. Management included antibiotics, drainage and operation.
      Four patients died due to the direct complications of liver abscess. One patient
      experienced total tumour resolution after successful treatment for liver abscess.
      Patients with larger liver abscesses and patients with greater age carried higher
      mortality rates. CONCLUSIONS: Liver abscess is a rare complication after TAE for
      hepatocellular carcinoma. Recurrent fevers after an initial symptom free interval
      should arouse suspicion of an abscess. The mortality is high and a large abscess
      and higher age predict an unfavourable outcome. Abscess formation can lead to
      complete tumour resolution.

PMID- 15256975
TI  - New Doppler ultrasound signs improve the non-invasive diagnosis of cirrhosis or
      severe liver fibrosis.
AB  - OBJECTIVES: To determine whether ultrasound and, particularly, new Doppler signs
      increased the diagnostic accuracy of the most accurate, currently available
      markers for the diagnosis of cirrhosis or severe fibrosis. METHODS: Thirty-two
      clinical (n = 4), biochemical (n = 11) and Doppler ultrasound (n = 17) variables
      were recorded in 106 patients with compensated chronic liver disease. Diagnostic
      accuracy was evaluated by discriminant analysis; first, globally, using all
      variables then by stepwise analysis. RESULTS: (A) Diagnosis of cirrhosis. Using
      Doppler ultrasound, diagnostic accuracy was 92% (95% confidence interval 81-98)
      globally, and 89% (76-95) with three variables (spleen length, hepatic vein
      spectrum and maximum portal vein velocity). Based upon clinical signs, diagnostic
      accuracy was 86% (77-92) globally, and 85% (76-91) with one variable (firm
      liver). Based upon biochemical parameters, diagnostic accuracy was 80% (70-88)
      globally, and 81% (72-88) with two variables (hyaluronate and platelet count).
      Based upon all parameters, diagnostic accuracy was 91% (79-96.5) globally, and
      91% (79-96.5) with four variables (firm liver, hyaluronate, platelet and hepatic
      vein spectrum). On an intention to diagnose basis, Doppler ultrasound provided a
      lower independent contribution due to missing data. (B) In the diagnosis of
      severe fibrosis, diagnostic accuracy was 83% (69-92) globally, and 77% (62-87)
      with one variable. CONCLUSIONS: Cirrhosis can be correctly diagnosed in
      approximately 90% of patients with compensated chronic liver disease using a few
      Doppler ultrasound signs including a new sign, the hepatic vein spectrum. Doppler
      ultrasound could be used for the first line diagnosis and biochemical markers,
      such as hyaluronate, in patients with missing Doppler ultrasound data.

PMID- 15256976
TI  - Insulin-like growth factor I gene microsatellite repeat, collagen type Ialpha1
      gene Sp1 polymorphism, and bone disease in primary biliary cirrhosis.
AB  - BACKGROUND: Genetic factors have been implicated in the pathogenesis of
      osteoporosis, a common disorder in primary biliary cirrhosis. Insulin-like growth
      factor I (IGF-I) gene microsatellite repeat polymorphism was found to be
      associated with osteoporosis in some studies, and collagen-Ialpha1 (COLIA1) Sp1 s
      allele was associated with lower bone mineral density in primary biliary
      cirrhosis. IGF-I treatment restored osteopenia and reduced fibrogenesis in
      experimental cirrhosis. We investigated IGF-I and COLIA1 gene polymorphisms and
      bone mineral density in Hungarian primary biliary cirrhosis patients. PATIENTS
      AND METHODS: Seventy female patients with primary biliary cirrhosis were enrolled
      (mean age 57.6 years, range 37-76 years; all anti-mitochondrial antibody M2
      positive; stage II-IV). One hundred and thirty-nine age-matched female subjects
      served as controls (mean age 55.9 years, range 43-72 years). COLIA1 and IGF-I
      polymorphisms were determined by polymerase chain reaction. Bone mineral density
      was measured by dual-energy X-ray absorptiometry in the lumbar spine and femoral
      neck. RESULTS: The IGF-I was not different between primary biliary cirrhosis
      patients and controls. The genotype frequency of COLIA1 polymorphism was also not
      different between primary biliary cirrhosis patients and controls. However, the s
      allele was significantly less frequent in patients with primary biliary
      cirrhosis. Osteoporosis was detected in 22 patients. The IGF-I 192/192 genotype
      was associated with higher femoral-neck z-scores compared with other genotypes.
      CONCLUSION: In contrast to previous studies, the s allele was less frequent in
      patients with primary biliary cirrhosis, and its presence was not associated with
      bone mineral density. Since IGF-I polymorphism was associated with bone mineral
      density, it may be hypothesised that not COLIA1 but IGF-I together with other
      genetic and environmental factors may be involved in the complex regulation of
      bone mineral density in primary biliary cirrhosis.

PMID- 15256977
TI  - Tumour necrosis factor alpha polymorphisms are not involved in the development of
      steatosis in chronic hepatitis C.
AB  - AIM: To determine whether the different tumour necrosis factor alpha (TNF-alpha)
      promoter gene polymorphisms are involved in the development of steatosis in
      chronic hepatitis C. PATIENTS AND METHODS: One hundred and thirty patients (89
      men and 41 women; mean age 42.5 +/- 12.3 years) with chronic hepatitis C were
      included. Insulin resistance was measured according to the Homeostasis model
      assessment (HOMA IR). Serum leptin levels were also obtained and the body mass
      index and fat mass were calculated. Liver biopsy was carried out in all the
      patients, and steatosis was measured as one of four stages (0 to 3): stage 0, no
      steatosis; stage 1, < 25% of hepatocytes with steatosis; stage 2, 25-50%; and
      stage 3, > 50%. DNA samples were obtained in order to describe the polymorphisms
      at the TNF-alpha promoter gene position. RESULTS: Fifty-nine of the 130 (45.38%)
      patients had different degrees of steatosis, while 71/130 (54.62%) were not
      steatosic. Six of the 59 (10.2%) patients with steatosis presented mutations at
      the -238 position of the TNF-alpha promoter region, while 5/71 (7.0%) patients
      without steatosis also showed mutations at this position (P=NS). Seventeen of the
      59 (28.8%) steatosic patients showed a mutation at the -308 position, while 16/71
      (22.5%) without steatosis also had this mutation (P=NS). Insulin resistance, beta
      cells reserve, insulin and leptin levels showed no differences between patients
      with or without mutations at the promoter region of the TNF-alpha gene.
      CONCLUSIONS: TNF-alpha mutations do not seem to play any role in the development
      of steatosis in chronic hepatitis C.

PMID- 15256978
TI  - Austrian infliximab experience in Crohn's disease: a nationwide cooperative study
      with long-term follow-up.
AB  - OBJECTIVE: To determine the nationwide experience with infliximab for the
      treatment of Crohn's disease in Austria. DESIGN: National multicentre
      retrospective postal questionnaire survey. SETTING AND PARTICIPANTS: All
      institutions using infliximab for Crohn's disease in the years 1999 and 2000 were
      identified by the registry of the local provider of this drug. OUTCOME MEASURES:
      Response after first treatment course according to physician global assessment,
      number of subsequent infliximab infusions, disease activity at end of follow-up,
      avoidance of steroids, frequency of surgery for Crohn's disease, and adverse
      events. RESULTS: Questionnaires were returned by 32/35 (91%) centres approached.
      A total of 748 infusions were administered to 153 patients. After the first
      treatment course an excellent or good response occurred in 48/58 (83%) patients
      with luminal disease, and in 67/95 (71%) patients with fistulous disease (P <
      0.05). After the first treatment course 108 (71%) patients received further
      infliximab therapy. At a mean follow-up of 29 months, 50% of patients had
      improved since baseline without requiring surgery for Crohn's disease. Steroid
      withdrawal was achieved in 25% of patients. Surgery had been performed in one
      third of patients and was associated with lacking response to the first treatment
      course (P < 0.001) and with fistulous disease (P = 0.012). Co-medication with
      azathioprine favoured the initial response and steroid withdrawal (P < 0.05). One
      patient died from myocarditis; other adverse events were consistent with that
      seen in other studies of infliximab. CONCLUSIONS: The Austrian experience with
      infliximab for Crohn's disease is in general accordance with results from
      clinical trials and post-marketing studies from single centres. A substantial
      subgroup of patients appear to have a prolonged benefit from infliximab therapy.

PMID- 15256979
TI  - Enteric infection in relapse of inflammatory bowel disease: importance of
      microbiological examination of stool.
AB  - OBJECTIVE: Previous reports have suggested that diarrhoeal relapses of
      inflammatory bowel disease (IBD) may be associated or confused with enteric
      infection, and that treatment of such infections with appropriate antibiotics may
      be beneficial. To re-evaluate the suggestion that enteric infection is rare and
      microbiological testing of stool not routinely necessary in patients presenting
      with relapse of IBD, we have reviewed the incidence of concurrent infection in
      patients presenting in relapse over a recent 5-year period. METHODS: Stool
      microbiology results relating to relapses of IBD during the period 1997-2001 were
      obtained retrospectively. Relapse was confirmed by standard clinical,
      sigmoidoscopic and laboratory criteria. RESULTS: During the period 1997-2001
      there were 237 relapses in 213 patients. Enteric infection was found in 25
      (10.5%) relapses in 24 patients; in seven patients, infection was associated with
      the initial presentation of their IBD. Clostridium difficile toxin was detected
      in 13 (5.5%) instances; the 12 other infections (5% relapses) were Campylobacter
      spp. (five), Entamoeba histolytica (three), Salmonella spp. (one), Plesiomonas
      shigelloides (one), Strongyloides stercoralis (one) and Blastocystis hominis
      (one). There was a significant association between infection and the need for
      hospital admission. Of the 13 relapses associated with C. difficile, ten were in
      outpatients, seven patients had undergone previous antibiotic treatment, and four
      patients were presenting with IBD for the first time. All relapses resolved
      satisfactorily after treatment with antibiotics with or without corticosteroids.
      CONCLUSIONS: The high prevalence of enteric infections, of which C. difficile was
      the most common, indicates that all patients presenting with relapse of IBD
      should have stool examined microbiologically.

PMID- 15256980
TI  - Does the declining prevalence of Helicobacter pylori unmask patients with
      idiopathic peptic ulcer disease? Trends over an 8 year period.
AB  - OBJECTIVES: Recent studies have suggested that the prevalence of Helicobacter
      pylori infection in patients with ulcer disease who were not using non-steroidal
      anti-inflammatory drugs (NSAIDs) has been overestimated. The decreasing
      prevalence of H. pylori could lead to a relative increase in the number of
      patients with this idiopathic peptic ulcer disease (IPUD). This study aimed to
      investigate the prevalence of IPUD and any possible trends. DESIGN AND METHODS:
      The reports of all upper gastro-intestinal endoscopies performed in a Dutch
      regional hospital over the period 1991 to 1998 were reviewed. If a gastric and/or
      duodenal ulcer had been diagnosed, data concerning possible H. pylori infection
      (culture, histology, rapid in-house urease test) were retrieved. If H. pylori
      tests were negative, hospital files were examined for possible use of NSAIDs or
      other rare causes of ulcer disease. When these were not found, stored biopsy
      specimens were tested for H. heilmanii by using the polymerase chain reaction
      technique. RESULTS: Ulcer disease was diagnosed in 405 patients who had undergone
      endoscopy (159 with gastric ulcer, 235 with duodenal ulcer, and 11 with both
      gastric and duodenal ulcer). H. pylori infection was found in 349 of these
      patients (86.2%). Thirty-three of the 56 H. pylori negative patients used NSAIDs
      and three patients had Crohn's disease, leaving 20 patients with IPUD (4.9%, 12
      gastric ulcer and eight duodenal ulcer). Time trends over the study period showed
      a decrease of H. pylori associated peptic ulcer disease (P <0.002) and an
      increase of NSAID associated peptic ulcer disease (P <0.0005). The prevalence of
      IPUD remained stable (P=0.978). CONCLUSIONS: The prevalence of patients with H.
      pylori negative ulcer disease significantly decreased in our study population due
      to an increase in the number of patients with NSAID associated peptic ulcer
      disease. IPUD was rare and its prevalence did not increase over a period of 8
      years.

PMID- 15256981
TI  - Long-term follow-up of empirical treatment or prompt endoscopy for patients with
      persistent dyspeptic symptoms?
AB  - BACKGROUND: There are concerns about the safety and possible high costs of
      ongoing proton pump inhibitor therapy of empirical management strategies for
      patients with persistent dyspeptic symptoms. AIM: To compare the long-term
      results of two treatment strategies: empirical treatment followed by the
      Helicobacter pylori test and treat strategy (treat and test group) and prompt
      upper gastrointestinal endoscopy followed by directed medical treatment
      (endoscopy group). METHODS: In this study we describe the long-term follow-up
      data from a previously published randomized clinical trial. At least 6 years
      after randomization all participating general practitioners and patients were
      asked to give information about medication use, diagnostic testing, symptoms and
      quality of life by questionnaire. RESULTS: Information about a total of 77 out of
      the 80 patients initially included (96%) was retrieved. Overall, 16 patients from
      the treat and test group (41%) underwent 18 diagnostic investigations. The 34
      patients (100%) from the endoscopy group underwent 38 investigations (P < 0.01).
      The number of patients of the treat and test group and endoscopy group using acid
      inhibition therapy was 15 (38%) and 19 (56%), respectively (P = 0.14). There were
      also no differences in symptom prevalence and quality of life between the groups.
      CONCLUSIONS: Treat and test management for patients with dyspeptic symptoms is
      safe and does not lead to additional diagnostic testing or use of medication when
      compared to prompt endoscopy.

PMID- 15256982
TI  - Oesophageal carcinoma and refractory idiopathic thrombocytopenic purpura: a
      challenging combination.
AB  - We report the case of a 72-year-old lady who presented with fatigue and bruising.
      Initial investigations were compatible with iron deficiency anaemia and
      idiopathic thrombocytopenic purpura (ITP). The anaemia and recent heartburn
      symptoms led to endoscopy, which revealed an extensive oesophageal squamous cell
      carcinoma. The tumour was inoperable due to local extension and the patient was
      not deemed fit enough for aggressive chemotherapy. A course of radical local
      radiotherapy was given. The patient's ITP, which had initially been responsive to
      high-dose intravenous immunoglobulin, subsequently became refractory to all
      therapeutic modalities. The patient developed significant dysphagia but
      therapeutic options were limited due to her severe thrombocytopenia. The patient
      eventually died from a combination of gastrointestinal and intrapulmonary
      haemorrhage. This case is of interest for two reasons. First, the development of
      refractory ITP appeared to mirror the progression of the carcinoma, and to our
      knowledge this is the first case of ITP associated with oesophageal carcinoma.
      Second, despite recent endoscopic advances in palliating oesophageal tumours,
      this case highlights the difficulties that can still occur.

PMID- 15256983
TI  - 111Indium-labelled red-cell scintigraphy to detect intermittent gastrointestinal
      bleeding from synchronous small- and large-bowel adenocarcinomas.
AB  - A 70-year-old woman presented with symptoms of profound anaemia and evidence of
      intermittent gastrointestinal haemorrhage. Oesophagogastroduodenoscopy,
      colonoscopy, abdominal computerised tomography, sulphur colloid scintigraphy and
      selective mesenteric angiography were non-diagnostic. An indium-labelled red-cell
      scan was performed, which suggested bleeding from the ileum at 36 h. At
      laparotomy, a primary small-bowel adenocarcinoma was resected. Six weeks later,
      she was again anaemic. Repeat colonoscopy showed a synchronous primary colonic
      adenocarcinoma, which had been masked by intraluminal blood during the original
      indium scan. The lesion was impalpable, even after full mobilisation of the
      colon. A right hemicolectomy was performed. Indium has a longer half-life (67 h)
      than the more commonly used technetium isotope (18 h). This allows serial imaging
      for up to 5 days, which may increase diagnostic efficiency in intermittent
      gastrointestinal bleeding. Clinicians should be aware that persisting activity
      from intraluminal blood may mask synchronous lesions.

PMID- 15256984
TI  - Polyarteritis nodosa associated with hepatitis B virus infection. The role of
      antiviral treatment and mutations in the hepatitis B virus genome.
AB  - Polyarteritis nodosa (PAN) is a systemic inflammatory disease causing vasculitis
      of medium sized and small arteries. Circulating immune complexes containing viral
      proteins have been implicated in the pathogenesis of hepatitis B virus (HBV)
      related PAN and several immunosuppressive and antiviral regimens have been used
      with varying success. In our hospital seven HBV positive patients with a
      confirmed diagnosis of PAN could be identified between 1984 and 2001. Most
      patients had an acute HBV infection and all patients were treated with
      prednisone. A combination of prednisone and antiviral therapy with alpha
      interferon (IFN) was used only in the last four patients. HBV DNA was isolated
      from serum samples obtained before treatment from the four IFN treated patients
      and amplified by using the polymerase chain reaction technique. None of the
      patients without, but two of four with antiviral therapy exhibited HBsAg
      seroconversion. In three out of four patients HBV DNA decreased rapidly after
      starting IFN therapy. Clinical remission of PAN was observed in three of the four
      treated patients, but in none of the three patients who were not receiving
      antiviral medication. Analysis of the HBV genome revealed no mutations that could
      be associated with PAN. In one patient a stop codon in the pre-core region and a
      double mutation A1762T-G1764A were found during antiviral therapy. We did not
      find HBV heterogeneity predisposing to the development of PAN. In our group of
      patients it appeared that clinical remission of PAN was primarily related to
      spontaneous or therapy induced loss of HBV DNA replication. The combined
      administration of a priming steroid course and IFN appears to be an improvement
      over prednisone monotherapy and should be considered for every patient with HBV
      related PAN. The efficacy of new generation nucleoside analogues should be
      further elucidated in future studies.

PMID- 15256985
TI  - Pancreatitis, alcohol and immunoglobulin E.

PMID- 15256988
TI  - Eye rubbing can cause keratoconus.

PMID- 15256989
TI  - Frequency, distribution, and outcome of keratoplasty for corneal dystrophies at a
      tertiary eye care center in South India.
AB  - PURPOSE: To report the frequency, outcome, and atypical histology in corneal
      dystrophies. METHODS: Corneal buttons of patients diagnosed with corneal
      dystrophy as noted in the records of the ophthalmic pathology register over a
      period of 6 years were included in this study. The sections from formalin-fixed,
      paraffin-embedded tissues were reviewed specifically for the type of deposits,
      associated degenerations such as amyloid and spheroidal deposits, inflammation,
      and vascularization. Special stains including Masson trichrome, Congo red, and
      Alcian blue staining were used whenever required. The medical records were
      evaluated for demographics, clinical presentation, history of consanguinity,
      family medical history, and clinical outcome of keratoplasty, which was recorded
      as clear, recurrence of dystrophy, or graft failure. A clinicopathologic
      correlation was attempted. RESULTS: A total of 144 patients contributed 181
      buttons, accounting for 8.1% of keratoplasties performed during the study period.
      The mean age of the patients was 34 +/- 19 years (range 3-72 years) with a
      male:female ratio of 1.6 (89):1 (55). Consanguineous parentage was noted in 26%
      of cases. History of a similar problem in siblings and other family members was
      elicited in 33 (22%) and 14 (9.7%), respectively. Dystrophies included macular
      (29.3%), congenital hereditary endothelial dystrophy (34.8%), Fuchs (16.6%), and
      lattice (15%); the remaining 11% included granular, gelatinous drop-like, Reis
      Bucklers, and posterior polymorphous dystrophy. Associated histologic changes
      were degenerations (15%), vascularization (4%), and inflammation (2%). At a mean
      follow-up of 42 months, the graft remained clear in 148 eyes (81.7%), failed in
      33 eyes (18.2%), and recurred in 5 eyes (2.8%). Graft survival for all
      dystrophies at the end of 1 year was 94.3 +/- 1.7%, and at the end of 5 years was
      74.4 +/- 4.5%. Atypical histologic features did not affect graft survival.
      CONCLUSION: Consanguineous marriages possibly contributed to the increase in
      macular dystrophy and CHED in South India. The degenerative changes seen could
      possibly be related to late presentation or unknown environmental factors and do
      not have an effect on the ultimate graft outcome.

PMID- 15256990
TI  - Corneal infections after implantation of intracorneal ring segments.
AB  - PURPOSE: To report risk factors, clinical course, and outcome in patients with
      infectious keratitis following implantation of intracorneal ring segments (ICRS).
      METHODS: The records of 8 patients with culture-proven infectious keratitis after
      ICRS (Ferrara or Intacs) implantation were retrospectively reviewed. Age, gender,
      corneal findings, ocular abnormalities, the condition that led to ICRS
      implantation, immediate prior use of a contact lens, elapsed time between
      implantation and the onset of symptoms, previous medications, and systemic
      disorders were noted. RESULTS: Culture-positive infectious keratitis developed in
      7 eyes of 7 patients (2 men and 5 women) with a mean age of 35 years who
      underwent Ferrara implantation for the treatment of keratoconus and in a 29-year
      old man who underwent Intacs implantation for correction of low myopia. Contact
      lens use, diabetes, and trauma were factors possibly associated with the risk of
      infection in three cases. Microorganisms, identified in all cases, included
      Staphylococcus aureus, Streptococcus viridans, Streptococcus pneumoniae,
      Pseudomonas sp, Nocardia sp, Klebsiella sp, and Paecylomices sp. Onset of
      symptoms of infection varied from less than 1 week to 22 months postoperatively,
      depending on the infecting organism. CONCLUSIONS: Infectious keratitis following
      ICRS implantation is a sight-threatening complication for which early recognition
      and rapid institution of appropriate treatment may result in a better visual
      outcome.

PMID- 15256991
TI  - Effect of topical 0.1% indomethacin solution versus 0.1% fluorometholon acetate
      on ocular surface and pain control following laser subepithelial keratomileusis
      (LASEK).
AB  - PURPOSE: To compare the effect of topical 0.1% indomethacin solution versus 0.1%
      fluorometholon acetate in the early postoperative period after LASEK treatment.
      METHODS: One hundred thirty-five patients undergoing LASEK, having been
      randomized in a double-masked manner into 2 groups (1 receiving indomethacin and
      1 fluorometholon), were evaluated 2-4 days before and 4 days after treatment. We
      examined corneal fluorescein staining and corneal esthesiometry; the level of
      pain experienced was reported by the patient on a visual pain scale. In addition,
      haze was evaluated at 14 +/- 1 weeks after surgery. RESULTS: The pain level and
      corneal fluorescein staining were significantly less in the indomethacin group.
      Corneal esthesiometry was reduced to the same extent in the 2 groups. There were
      no statistically significant differences in haze presentation between the 2
      groups. CONCLUSION: Our study highlights the efficacy of indomethacin solution
      compared with fluorometholon as a pain reducer after LASEK treatment and suggests
      that indomethacin is associated with a faster epithelial healing process.

PMID- 15256992
TI  - Outcome of combined Ahmed glaucoma valve implant and penetrating keratoplasty in
      refractory congenital glaucoma with corneal opacity.
AB  - PURPOSE: To investigate surgical outcomes following simultaneous Ahmed glaucoma
      valve implant and penetrating keratoplasty (PKP) in the management of refractory
      congenital glaucoma with corneal opacity. METHODS: A retrospective review was
      undertaken of pediatric patients who underwent simultaneous Ahmed glaucoma valve
      implant and PKP at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia,
      between January 1994 and September 1999. RESULTS: Twenty eyes of 17 patients were
      included in the study. Cumulative probabilities of success by Kaplan-Meier
      analysis showed 85%, 44%, and 33% IOP control and 85%, 43%, and 17% graft success
      at 2, 24, and 48 months. The most common cause of glaucoma failure that required
      subsequent surgery was subconjunctival scarring, which resulted in loss of long
      term IOP control. Main graft-related complications included failure (13/20) and
      graft ulceration (6/20), and in 4/6 ulcerated grafts, Streptococcus pneumoniae
      was cultured positively. Subsequent surgery was the only significant clinical
      factor associated with poor outcome of glaucoma. However, low graft survival rate
      was significantly associated with delinquency of follow-ups, corneal ulcer,
      subsequent surgery, and postoperative complications. CONCLUSIONS: The long-term
      success of simultaneous Ahmed glaucoma valve implant and PKP in refractory
      congenital glaucoma associated with corneal opacity is low, and the complication
      rate is high.

PMID- 15256993
TI  - Asymmetric keratoconus attributed to eye rubbing.
AB  - PURPOSE: To report a series of cases with asymmetric keratoconus attributed to
      eye rubbing, discuss its pathogenesis, and review the literature. METHODS: Case
      reports and literature review. RESULTS: A careful history obtained from 5
      patients with asymmetric keratoconus revealed habitual eye rubbing of the more
      severely affected eye. CONCLUSIONS: Trauma, such as occurs with habitual eye
      rubbing, plays a role in the pathogenesis of keratoconus.

PMID- 15256994
TI  - Congenital corneal opacities in a cornea referral practice.
AB  - PURPOSE: To address the primary causes of the congenital corneal opacities seen
      on the Cornea Service at Wills Eye Hospital (Philadelphia, PA), the associated
      systemic anomalies and their management. METHODS: Retrospective review of the
      medical records of all patients with the diagnosis of congenital corneal
      opacities seen at the Cornea Service from January 1, 1992 to June 30, 2003.
      Children 12 years old or younger at the first visit to our department were
      included in the study. We classified the location and extent of corneal
      pathology. We divided the management into medical and surgical. RESULTS: Seventy
      two eyes of 47 patients were included in the study. The mean follow-up time from
      the first to the last visit was 33.1 months. The most common primary cause of
      congenital corneal abnormalities was Peters anomaly (40.3%), followed by
      sclerocornea (18.1%), dermoid (15.3%), congenital glaucoma (6.9%), microphthalmia
      (4.2%), birth trauma, and metabolic disease (2.8%). Seven eyes (9.7%) were
      classified as idiopathic. Ten patients had systemic abnormalities associated with
      their ocular condition. The management was medical in 38 eyes (52.7%). Twenty
      four eyes (32.4%) underwent only 1 penetrating keratoplasty (PK). Only 1 eye
      received a regraft during the follow-up period. Eight grafts failed during the
      follow-up period. CONCLUSION: The importance of this study is to share our
      experience with this rare entity, congenital corneal opacities, describing their
      clinical presentation and their management.

PMID- 15256995
TI  - Pigmented plaque presentation of dematiaceous fungal keratitis: a
      clinicopathologic correlation.
AB  - PURPOSE: To evaluate the clinical, microbiologic, and histopathologic features of
      dematiaceous fungal keratitis cases presenting with pigmented, raised, plaque
      like infiltrate. STUDY DESIGN: Consecutive case series. METHODS: Microbiology
      proven cases of fungal keratitis presenting with a pigmented infiltrate were
      included in the study. A detailed clinical and microbiological evaluation was
      performed in all cases. The lesion was removed by superficial keratectomy, and
      the specimen was subjected to histopathologic examination. Patients presenting
      with a large infiltrate had penetrating keratoplasty, and the corneal button was
      submitted for histopathology examination. RESULTS: We enrolled 15 cases in the
      study. There were 11 men and 4 women. The mean age of the patients was 48.5 years
      (range 27-68 years). The patients presented to us with duration of symptoms
      ranging from 7 to 60 days (mean 27.6 +/- 15.6, median 30). The visual acuity was
      better than 20/200 in 9 (60%) cases. The infiltrate size varied from 4.3 to 64
      mm2 (mean 26.9 +/- 16.6, median 22.5). Ten (66.7%) cases had a central
      infiltrate. The infiltrate was dry and raised, with brown to black pigmentation
      on its surface. Corneal scrapings revealed septate fungal filaments in all cases
      and the characteristic brown to black pigmentation of the fungal cell wall in 10
      (66.7%) cases. Although there was a significant growth of dematiaceous fungi on
      culture in all cases, species identification could be done in 3 cases only.
      Examination of tissue sections revealed a carpet of pigmented fungal filaments on
      the corneal surface (n = 12, 92.3%) associated with mild to moderate inflammation
      (n = 11, 84.7%) and tissue destruction. Nine out of 11 cases that had keratectomy
      resolved with medical therapy. CONCLUSIONS: The pigmented plaque-like infiltrate
      in dematiaceous fungal keratitis consists of surface colonization of pigmented
      fungal filaments associated with mild to moderate inflammation and tissue
      destruction of the underlying corneal stroma.

PMID- 15256996
TI  - Multilayer amniotic membrane transplantation in the treatment of corneal
      perforations.
AB  - PURPOSE: To determine if multilayer amniotic membrane transplantation (AMT) is
      useful in the treatment of corneal perforations, and in particular to assess to
      what extent efficacy is affected by perforation size. METHODS: Fifteen patients
      (15 eyes) with corneal perforations of different sizes were divided into 3
      groups: group A (microperforation, 6 eyes), group B (0.5-1.5 mm, 4 eyes), and
      group C (>1.5 mm, 5 eyes). The corneal perforation was caused by autoimmunity
      related ulcer (3 eyes), neurotrophic ulcer (9 eyes), infectious keratitis (1
      eye), or postkeratoplasty ulcer (2 eyes). Two layers of AM (for
      microperforations) or 3-4 layers (for the other groups) were trimmed to the size
      of the ulcer and sutured in place with interrupted 10-0 nylon sutures. In all
      cases, a bandage contact lens was then applied. RESULTS: Mean epithelialization
      time was 3.7 weeks (range 2-6). Mean time to recovery of corneal stroma thickness
      was 10.1 weeks (range 7-15). In all cases, ocular inflammation subsided within 2
      5 weeks. The treatment was judged successful in 73% (11/15) of eyes. Three of the
      4 unsuccessful treatments were of perforations 3 mm or more in diameter; of the 5
      eyes with perforations of more than 1.5 mm in diameter, only 2 were treated
      successfully. CONCLUSIONS: These results suggest that multilayer AMT is effective
      for treating corneal perforations with diameter less than 1.5 mm. The technique
      may be a good alternative to penetrating keratoplasty, especially in acute cases
      in which graft rejection risk is high.

PMID- 15256997
TI  - Changing indications for corneal transplantation at the King Khaled Eye
      Specialist Hospital (1983-2002).
AB  - PURPOSE: To identify changing indications for keratoplasty over the last 20 years
      at a tertiary care eye hospital in a country with rapidly evolving ophthalmic
      care services. METHODS: A retrospective review was performed of the eye bank
      records of every patient who received a lamellar or penetrating keratoplasty at
      the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, between January
      1, 1983 and December 31, 2002. For each case, the primary surgical indication was
      identified. RESULTS: A total of 8318 corneal transplants were performed during
      this 20-year period. In the first 5 years of the study, the leading indications
      for corneal transplantation were corneal scarring (52.0%), aphakic/pseudophakic
      bullous keratopathy (13.5%), corneal degeneration (10.0%), and keratoconus
      (7.6%). During the last 5 years of the study, the leading indications for corneal
      transplantation were keratoconus (40.2%), corneal scarring (19.8%), failed
      corneal transplant (11.3%), and corneal ulceration (10.2%). There was a dramatic
      increase in the number of transplants performed for keratoconus (441%) and failed
      corneal transplants (285%) as well as a dramatic decrease in the number of
      transplants performed for corneal degeneration (-88%) and scarring (-60%) between
      the first and last 5 years of the study period. CONCLUSIONS: Major changes in the
      indications for corneal transplantation were related to the introduction and
      expansion of modern ophthalmic services at a time of rapid socioeconomic
      development and population growth.

PMID- 15256998
TI  - Penetrating keratoplasty in Nepal.
AB  - PURPOSE: To identify indications and outcomes in a large series of penetrating
      keratoplasty surgeries performed in Nepal. METHODS: A retrospective case series
      of 472 consecutive penetrating keratoplasty surgeries (408 patients) performed at
      Tilganga Eye Center, Kathmandu, Nepal from June 1994 to September 1999. RESULTS:
      Mean recipient age was 39.2 years (+/- 19.7 years). Main indications for PKP were
      corneal scar (37%), adherent leukoma (35%), perforation or impending perforation
      (9%), pseudophakic bullous keratopathy (6%), keratoconus (4%), and aphakic
      bullous keratopathy (3%). Mean duration of follow-up was 27.6 +/- 25.1 months.
      Sixty-five percent of available grafts were clear at 6 months, and 70% of
      available grafts were clear at 3 years. Six months postoperatively, 15% of
      patients had acuity better than 6/18, 37% had acuity between 6/18 and 6/60, and
      17.7% had acuity between 6/60 and 3/60. Common causes of graft failure were
      endothelial failure (43%), increased intraocular pressure (15%), ulcer (14%), and
      trauma (7%). CONCLUSIONS: The corneal diseases and indications for transplant
      surgery in Nepal are different from those in the Western world. Despite these
      differences, penetrating keratoplasty is a successful and reasonable way to
      reduce corneal blindness in developing nations.

PMID- 15256999
TI  - Factors affecting eye donation from postmortem cases in a tertiary care hospital.
AB  - PURPOSE: To evaluate the responses to requests for eye donation from relatives of
      postmortem cases in a tertiary care hospital in India. METHODS: In a prospective
      study, the cases brought for postmortem to the Forensic Medicine Department were
      screened as potential donors by our team. The next of kin of potential donors
      were approached and counseled in a systematic manner following a standard
      interview pattern. Responses were noted in a predesigned performa. The religion,
      level of literacy, socioeconomic status, relationship with the deceased, prior
      knowledge of eye donation, willingness for eye donation, and reasons for not
      donating eyes of the deceased were recorded. RESULTS: One hundred fifty-nine
      potential donors were identified from a total of 721 postmortem cases. There were
      119 (74.8%) men and 40 (25.2%) women. None of the deceased had previously pledged
      their eyes for eye donation. Eighty-eight (55.4%) next of kin were already aware
      of the concept of eye donation, but 71 (44.7%) families had not heard of it
      before. Willingness for eye donation was seen in 66 (41.5%), whereas 93 (58.5%)
      families refused eye donation. Of those already aware of eye donation, 39 (44.3%)
      gave consent for donation. Prior knowledge of eye donation had no influence on
      willingness for eye donation (P = 0.424). Similarly, literacy (P = 0.338) and
      socioeconomic status as estimated by a composite socioeconomic scale based on
      literacy and family income did not have any influence on willingness for eye
      donation (P = 0.338). Major reasons for not donating eyes included refusal to
      discuss the issue and dissuasion by distant relatives, legal problems, and
      religious beliefs. CONCLUSIONS: In our experience, literacy, socioeconomic
      status, and prior knowledge of eye donation of next kin had no correlation with
      donor corneal tissue procurement. Active counseling by a motivated team can be
      effective even in families with no prior knowledge and low socioeconomic status.

PMID- 15257000
TI  - Topographic patterns in refractive surgery candidates.
AB  - PURPOSE: To evaluate the prevalence of different topographic patterns in
      refractive surgery candidates and to estimate the extent of candidate rejection
      based on topography alone. METHODS: We performed a retrospective evaluation of
      videokeratographies of previously unoperated refractive surgery candidates. The
      defined topographic patterns of their corneas and the indices computed by the
      videokeratographer software were registered. The data were evaluated by SPSS/PC
      statistical software. RESULTS: One hundred candidate electronic topography
      records were evaluated. The candidates included 41 women and 59 men whose average
      age was 32 years (range 17.5-63.5). Their topographic patterns were: spherical
      (36/200 evaluated eyes), spherocylindrical (60), upper steep (32), lower steep
      (43), irregular astigmatism (9), decentered (3), suspected keratoconus (11), and
      probable keratoconus (6 eyes). Rejection from undergoing the procedure was based
      on topography alone in 27 of the 200 eyes. It was difficult to decide what to do
      with the 43 eyes with a lower steep pattern, and they were eventually rejected.
      Of the nine software-calculated indices, only one, "keratoconus index," could
      distinguish between the spherocylindrical and the lower steep patterns.
      CONCLUSIONS: More than one-half of corneal topographies of refractive surgery
      candidates did not comply with the assumed "normal" spherical or
      spherocylindrical patterns. The possible continuum of keratoconus-suspected
      keratoconus-lower steep pattern raises the question of where to draw the line
      between reasonable and risky when considering corneal refractive surgery.

PMID- 15257001
TI  - Surgical management of corneal plaques in vernal keratoconjunctivitis: a
      clinicopathologic study.
AB  - PURPOSE: To describe the surgical management and histopathologic and
      immunohistochemical findings in corneal plaques of shield ulcers in vernal
      keratoconjunctivitis. PATIENTS AND METHODS: Three children (ages 4, 7.5, and 9)
      presented with corneal plaques unresponsive to conservative systemic and topical
      medical treatment. Plaques were scraped under general anesthesia, and soft
      bandage contact lenses were placed. The excised tissue was evaluated by
      histopathology and immunohistochemistry. RESULTS: During surgery, plaques were
      found to extend beyond the ulcer margins. Histopathology revealed granular,
      deeply-eosinophilic, laminar material, firmly attached to the Bowman layer in all
      cases. Immunohistochemistry confirmed this to be eosinophil-derived major basic
      protein (MBP). After surgical removal, complete epithelization was evident within
      1-4 weeks in all cases. CONCLUSIONS: Corneal plaque is a rare complication of
      vernal keratoconjunctivitis. These plaques usually do not resolve with standard
      conservative measures. Failure to epithelialize may be a result of the plaque
      material extending below the edges of adjacent epithelium. We suggest that MBP
      plaques precipitate on the denuded stromal bed, thereby playing a pathogenic role
      in nonhealing shield ulcers.

PMID- 15257003
TI  - In vitro drug-induced spoliation of a keratoprosthetic hydrogel.
AB  - PURPOSE: To investigate in vitro the effects of selected drugs on the spoliation
      of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel
      currently used for the manufacture of a keratoprosthesis, AlphaCor. The
      experiments were carried out both in the presence of simulated aqueous humor
      (SAH) and in its absence. METHODS: Disks of PHEMA were incubated and shaken with
      9 commonly prescribed drugs at 37 degrees C in sterile conditions for 1 week.
      Samples were incubated either in SAH only (controls), in each drug preparation,
      or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this
      study were steroids (prednisolone, dexamethasone, fluorometholone,
      medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and
      antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially
      available formulations. Following incubation, the PHEMA specimens were examined
      visually and then histologically, after staining with alizarin red for the
      presence of calcium in the spoliating sediments/deposits. RESULTS: Although only
      5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML,
      pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and
      medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the
      absence of SAH, all drugs induced spoliation after postincubation in SAH, and
      calcium was detected in the majority of samples. The deposits on the hydrogel
      specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto
      Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain
      calcium, despite its presence in SAH. CONCLUSIONS: The study appears to confirm
      our earlier clinical observations that topical medication may play a role in the
      spoliation of the hydrogel ophthalmic devices. Presence of calcium in the
      deposits seems to be correlated to the nature of drug. Although the incidence of
      spoliation in real clinical situations is much lower than suggested by this
      extreme-case in vitro simulation, topical therapy after implantation of AlphaCor
      should be carefully considered, kept to the minimum required, and additive-free
      where possible.

PMID- 15257004
TI  - Ocular rosacea can mimic trachoma: a case of cicatrizing conjunctivitis.
AB  - PURPOSE: To report the case of a patient with upper eyelid chronic cicatrizing
      conjunctivitis and entropion, presumably secondary to ocular rosacea. METHODS:
      Case report and review of medical literature. RESULTS: The patient has a history
      of chronic cicatrizing conjunctivitis since 1999. Despite an extensive workup for
      other possible causes, the patient's known history of acne rosacea is the most
      substantive explanation for her ocular disease. CONCLUSION: The presence of
      chronic cicatrizing conjunctivitis affecting mainly the upper eyelids, previously
      thought to be unique to trachoma, can be associated with ocular rosacea.

PMID- 15257002
TI  - Rebamipide increases the amount of mucin-like substances on the conjunctiva and
      cornea in the N-acetylcysteine-treated in vivo model.
AB  - PURPOSE: Rebamipide increases the amount of mucin-like substances in the stomach.
      We aimed to determine the effects of rebamipide on the amount of mucin-like
      substances in the conjunctiva and cornea of N-acetylcysteine-treated eyes.
      Furthermore, we attempted to evaluate the effects of rebamipide on the wound
      healing of N-acetylcysteine-treated eyes. METHODS: The model was created by
      instilling 10% N-acetylcysteine solutions into rabbit eyes. Rebamipide was then
      applied on the day following the completion of N-acetylcysteine treatment. The
      amount of mucin-like substances on the conjunctiva and cornea was measured using
      the Alcian-blue binding method. The degree of damage was evaluated using scores
      based on the areas and densities of the cornea and conjunctival after staining
      using a rose Bengal solution under blind conditions. RESULTS: Rebamipide
      increased the level of mucin-like substances on the conjunctiva of N
      acetylcysteine-treated eyes when instilled at concentrations of 0.3% or higher,
      and 1% rebamipide increased the amount of mucin-like substances covering the
      cornea. Moreover, 1% rebamipide improved the rose Bengal scores of the cornea and
      conjunctiva in N-acetylcysteine-treated eyes. CONCLUSIONS: Rebamipide increased
      mucin-like substances on the cornea and conjunctiva of N-acetylcysteine-treated
      eyes. In accordance with the mucin-increasing effects, rebamipide improved the
      rose Bengal scores for the cornea and conjunctiva of N-acetylcysteine-treated
      eyes. However, the relevance of these findings to dry eyes is unclear because it
      is not known whether the change in mucus expression in the N-acetylcysteine model
      is similar to what occurs in aqueous tear deficiency. Consequently, it may be
      worth trying on an animal model of keratoconjunctivitis sicca.

PMID- 15257005
TI  - Congenital alacrima in Pierre Robin sequence.
AB  - PURPOSE: To report the presence of congenital alacrima in a patient with Pierre
      Robin (PR) sequence. METHODS: A 6-month-old child with diagnosed PR sequence
      presented to us with dysfunctional lacrimation present since birth. The child
      subsequently developed bilateral corneal ulcers. This unusual presentation and
      its management are described in detail, and other ocular associations of the PR
      sequence are discussed. RESULTS: Continuous tear supplementation and appropriate
      treatment with antibiotics controlled the microbial infection. However, the long
      term prognosis for visual rehabilitation remained poor in this patient because of
      the presence of central corneal opacities, persistent dry eye, which would
      preclude future optical keratoplasty, and possible sensory deprivation amblyopia.
      CONCLUSIONS: Alacrima can cause significant ocular morbidity, because persistent
      ocular surface dryness can be very difficult to manage. Lifelong tear
      supplementation may be necessary. The association or coexistence of congenital
      alacrima and the Pierre Robin sequence has not been described before this report.

PMID- 15257006
TI  - Pterygia with deep corneal changes.
AB  - PURPOSE: To report a series of patients with pterygia associated with deep
      corneal marks at the level of the endothelium and Descemet membrane previously
      unreported. METHODS: Clinical presentations of 7 patients (11 eyes) with pterygia
      and underlying deep corneal changes were reviewed for age, duration of pterygium,
      size of pterygium, and location of pterygium. Slit-lamp photos were obtained.
      Specular microscopy was performed on both eyes of 6 of these patients to evaluate
      the central endothelium and measure central corneal pachymetry. RESULTS: All
      patients were elderly (mean age 75 years, range 64-91) with long-standing nasal
      pterygia (average duration 43 years). The average size of the pterygium was 2.3
      mm (range 0.75-4.25 mm). All patients had significant ultraviolet-B exposure
      based on outdoor employment or hobbies. None of the patients had a family history
      of pterygia. Slit-lamp photos document marks at the level of the endothelium and
      Descemet membrane. All the deep corneal changes were underlying or directly
      adjacent to the pterygium. Pachymetry measurements of the central involved
      corneas averaged 531 +/- 41 microm. Central endothelial cell counts of the 9 eyes
      with endothelial changes averaged 1580 +/- 412 cells/mm2. CONCLUSIONS: Long
      standing nasal pterygia in elderly patients may rarely induce deep corneal
      changes at the level of the endothelium and Descemet membrane. Endothelial cell
      density may be lower in eyes with pterygia with deep corneal changes.

PMID- 15257007
TI  - Recurrence of Fuchs marginal keratitis within a lamellar graft.
AB  - We report a case of Fuchs marginal keratitis with a recurrence and spontaneous
      perforation on the lamellar graft. A constellation of marginal corneal
      infiltrates and stromal thinning under a pseudopterygium characterize this
      condition. Two years after an initial lamellar keratoplasty, the pathology
      recurred within the graft. A repeat lamellar keratoplasty was performed, this
      time combined with a conjunctival autograft.

PMID- 15257008
TI  - Recurrent herpetic keratouveitis following YAG laser peripheral iridotomy.
AB  - OBJECTIVE: To report recurrent herpetic keratouveitis following YAG laser
      peripheral iridotomy. METHODS: Case report. RESULTS: A 64-year-old woman with a
      history of dendritic keratitis underwent Nd:YAG laser peripheral iridotomy and
      developed geographic epithelial keratitis with stromal keratouveitis. Culture of
      a corneal swab grew herpes simplex virus type I. Keratouveitis subsided with
      acyclovir and corticosteroid therapy. CONCLUSIONS: Recurrent herpetic
      keratouveitis may be induced by YAG laser iridotomy.

PMID- 15257009
TI  - Corneal lamellar flap retraction after LASIK following penetrating keratoplasty.
AB  - PURPOSE: To describe a case of lamellar flap retraction after laser in situ
      keratomileusis (LASIK) to correct myopia and astigmatism after penetrating
      keratoplasty (PKP). METHODS: Eleven months after PKP, a 34-year-old man underwent
      uneventful LASIK. Preoperative manifest refraction was -5.50 + 4.00 x 55, giving
      a best-corrected visual acuity (BCVA) of 20/20. Three days after LASIK, the
      central cornea was clear with a 1- to 2-mm displacement and marked swelling of
      the inferior edge of the lamellar corneal flap, without central striae. The
      patient's uncorrected visual acuity (UCVA) was 20/60. The flap was repositioned,
      sutured with 6 10-0 nylon interrupted sutures, and covered with a bandage contact
      lens. RESULTS: Five months after the repair, the cornea was clear, UCVA was
      20/400, and manifest refraction was -9.50 + 6.00 x 75, giving a BCVA of 20/60.
      Three years later, manifest refraction was - 9.00 + 4.00 x 70, giving a BCVA of
      20/40+2. CONCLUSION: In LASIK surgery after PKP, there is a risk of flap edema
      leading to retraction of the transplant wound. It may therefore be advisable to
      wait at least 1-2 years after PKP before performing LASIK. Patients who have
      corneal transplants should also be warned that they might have unique risks in
      LASIK treatment that may result in the loss of vision.

PMID- 15257010
TI  - Efficacy of transport media use versus direct inoculation of blood agar plates in
      the microbiologic evaluation of experimental Streptococcus pneumoniae keratitis.

PMID- 15257011
TI  - Prothrombin time international normalized ratio monitoring by self-testing.
AB  - PURPOSE OF REVIEW: The increasing numbers of patients on oral anticoagulants may
      challenge the traditional organization of patient monitoring. The availability of
      portable coagulometers capable of measuring prothrombin time (PT) international
      normalized ratio (INR) in a drop of capillary blood facilitates decentralization
      of monitoring by self-testing. This article reviews the literature on use of
      portable coagulometers. RECENT FINDINGS: Numerous studies have evaluated the
      reliability of portable coagulometers in testing the PT-INR. This has been
      assessed by statistically as well as clinically relevant criteria. Other studies
      have been devoted to developing calibration models fulfilling the criteria
      recommended by the World Health Organization (WHO) for the calibration of INR
      measuring systems. Finally, studies have assessed the value of schemes for
      patient training and for the long-term quality assurance of portable
      coagulometers. SUMMARY: It can be concluded from the published studies that PT
      INR self-testing may be considered as a suitable alternative to conventional
      laboratory testing. For the PT-INR to be reliable, manufacturers of portable
      coagulometers should calibrate their devices against international standards for
      thromboplastin with procedures similar to those recommended by WHO for
      conventional measuring systems. Training of patients and implementation of
      appropriate quality assessment schemes are also essential prerequisites for the
      success of PT-INR self-testing.

PMID- 15257012
TI  - Factor VIII alloantibodies in hemophilia.
AB  - PURPOSE OF REVIEW: The development of an inhibitory response to factor VIII
      (FVIII) remains a puzzling challenge both for clinicians and scientists, not to
      mention the difficulties of maintaining hemostasis in patients producing
      inhibitors. RECENT FINDINGS: Three main research lines have been explored in
      recent months. The mechanisms by which an anti-FVIII antibody response is
      elicited in patients has been examined at both the B- and T-cell levels, with
      particular emphasis on the generation of specific B- and T-cell clones. The
      hemophilia A mouse model has served to confirm the main characteristics of the
      anti-FVIII immune response in terms of T-cell dependency and memorization of the
      response. Novel strategies for the prevention and downregulation of inhibitors
      have emerged, with special interest in antigen-specific approaches. SUMMARY:
      Although the ultimate goal, preventing or suppressing inhibitor formation in
      patients, is not yet achieved, the research activity developed over the past
      months brings us forward in that direction.

PMID- 15257013
TI  - Pathophysiologic roles of the fibrinogen gamma chain.
AB  - PURPOSE OF REVIEW: Fibrinogen binds through its gamma chains to cell surface
      receptors, growth factors, and coagulation factors to perform its key roles in
      fibrin clot formation, platelet aggregation, and wound healing. However, these
      binding interactions can also contribute to pathophysiologic processes, including
      inflammation and thrombosis. This review summarizes the latest findings on the
      role of the fibrinogen gamma chain in these processes, and illustrates the
      potential for therapeutic intervention. RECENT FINDINGS: Novel gamma chain
      epitopes that bind platelet integrin alpha IIbbeta3 and leukocyte integrin
      alphaMbeta2 have been characterized, leading to the revision of former dogma
      regarding the processes of platelet aggregation, clot retraction, inflammation,
      and thrombosis. A series of studies has shown that the gamma chain serves as a
      depot for fibroblast growth factor-2 (FGF-2), which is likely to play an
      important role in wound healing. Inhibition of gamma chain function with the
      monoclonal antibody 7E9 has been shown to interfere with multiple fibrinogen
      activities, including factor XIIIa crosslinking, platelet adhesion, and platelet
      mediated clot retraction. The role of the enigmatic variant fibrinogen gamma
      chain has also become clearer. Studies have shown that gamma chain binding to
      thrombin and factor XIII results in clots that are mechanically stiffer and
      resistant to fibrinolysis, which may explain the association between
      gammaA/gamma' fibrinogen levels and cardiovascular disease. SUMMARY: The
      identification of new interactions with gamma chains has revealed novel targets
      for the treatment of inflammation and thrombosis. In addition, several exciting
      studies have shown new functions for the variant gamma chain that may contribute
      to cardiovascular disease.

PMID- 15257014
TI  - Cellular microparticles: a disseminated storage pool of bioactive vascular
      effectors.
AB  - PURPOSE OF REVIEW: Microparticles (MP) or microvesicles are fragments shed from
      the plasma membrane of stimulated or apoptotic cells. Having long been considered
      inert debris reflecting cellular activation or damage, MP are now acknowledged as
      cellular effectors involved in cell-cell crosstalk. This review focuses on
      procoagulant MP circulating in the vascular compartment, their role in hemostasis
      and thrombosis, and possible impact in vascular functions. RECENT FINDINGS:
      Microparticles can be viewed as a "storage pool" by themselves, disseminating
      blood-borne tissue factor activity and procoagulant phospholipids. Increasing
      evidences of integrated loops involving dynamic exchanges and transfer events
      through multiple MP-cell interactions are summarized. SUMMARY: Microparticles can
      be considered true targets in the pharmacological control of thrombosis. Another
      challenging issue is to take advantage of their procoagulant potential for the
      management of hemophilia.

PMID- 15257015
TI  - Antiphospholipid antibodies: update on detection, pathophysiology, and treatment.
AB  - PURPOSE OF REVIEW: The antiphospholipid syndrome is a noninflammatory disease
      characterized by the presence of antiphospholipid antibodies in the plasma of
      patients with venous or arterial thrombosis or obstetric complications.
      Understanding of the pathology of the syndrome is only rudimentary and no
      physician can pretend that treatment is adequate. It is not possible to identify
      patients with the syndrome for certain. This paper reviews the substantial and
      promising headway made in the past year. RECENT FINDINGS: It has become clear
      that lupus anticoagulant is the assay of choice to detect the syndrome and that
      antibodies directed towards beta2Glycoprotein 1 are the clinical relevant
      autoantibodies. These antibodies are able to activate a number of cells involved
      in the regulation of hemostasis. SUMMARY: The latest developments will make it
      soon possible to define patient with the syndrome unambiguously. This is
      absolutely necessary to understand why the presence of antiphospholipid
      antibodies cause an increased thrombotic risk.

PMID- 15257016
TI  - Thrombin generation assays: accruing clinical relevance.
AB  - PURPOSE OF REVIEW: After decades of near oblivion, thrombin generation is being
      revived as an overall function test of the plasmatic coagulation system in
      platelet-poor plasma (PPP). In platelet-rich plasma (PRP) it assesses platelet
      procoagulant functions as well. RECENT FINDINGS: The recently developed use of
      special fluorogenic thrombin substrates allows monitoring of thrombin
      concentration in clotting PPP and PRP on line in up to 24 parallel samples.
      Studies in model systems stress the importance of cell-bound thrombin generation
      such as measured in PRP. SUMMARY: The method can be profitably applied to various
      hitherto unyielding problems such as the control of (low-molecular-weight)
      heparin therapy, the detection of lupus anticoagulant, and various forms of
      thrombomodulin and activated protein C resistance (including the use of oral
      contraceptives) as well as monitoring the treatment of hemophiliacs by factor
      VIII bypassing therapy. In PRP it reflects the abnormalities encountered in von
      Willebrand disease and Glanzmann and Bernard-Soulier thrombopathy as well as the
      action of antiplatelet drugs.

PMID- 15257017
TI  - Factor V Leiden: a disorder of factor V anticoagulant function.
AB  - PURPOSE OF REVIEW: Activated protein C (APC) resistance, which is often
      associated with the factor V R506Q (FV Leiden) mutation, is a common risk factor
      for venous thrombosis. Study of the mechanism of APC resistance has revealed that
      coagulation FV stimulates the APC-catalysed inactivation of FVIIIa, and that this
      anticoagulant function of FV is impaired in FV Leiden. The present review covers
      the discovery, the physiological significance and the structural requirements of
      the APC-cofactor activity of FV. RECENT FINDINGS: Recent in vitro and in vivo
      experiments indicate that the anticoagulant activity of FV is physiologically
      relevant and that FV plays a major role in the maintenance of the haemostatic
      balance. Quantitative and functional defects of the APC-cofactor activity of FV
      lead to increased thrombin generation and are associated with a prothrombotic
      state. Although the structural requirements for the expression of the APC
      cofactor activity of FV are now beginning to be unravelled, the underlying
      molecular mechanism remains elusive. SUMMARY: The APC-cofactor activity of FV and
      its impairment in FV Leiden can explain the different thrombosis risks associated
      with heterozygosity, homozygosity and pseudo-homozygosity for FV Leiden.
      Elucidation of the molecular mechanism of the anticoagulant function of factor V
      may provide novel targets for the design of antithrombotic drugs.

PMID- 15257018
TI  - Appropriate level and length of postthrombotic warfarin treatment: an evaluation
      of recent developments.
AB  - Current treatment and secondary prophylaxis of venous thromboembolism has two
      major drawbacks. During vitamin K antagonist therapy, patients need to be
      monitored closely to maintain efficacy and minimize the bleeding risk due to
      fluctuations of the prothrombin time (international normalized ratio, INR), and
      after cessation of therapy there is the problem of recurrent thrombosis, ie, the
      catch-up phenomenon. Recent studies indicate that for most patients, vitamin K
      antagonist therapy aimed at an INR of 2.0 to 3.0 is optimal. For patients with
      thrombosis due to a temporary risk factor, extending treatment beyond 3 months is
      not needed, whereas for other patients a minimal duration of 1 year can be
      advocated. For patients with cancer, it is beneficial to postpone therapy with
      vitamin K antagonists and prolong initial low-molecular-weight therapy for 3 to 6
      months. New developments are aimed at further individualization of the duration
      of treatment and at the introduction of agents that are suitable for long-term
      treatment and do not require monitoring.

PMID- 15257019
TI  - Antithrombotic therapy and cancer.
AB  - PURPOSE OF THE REVIEW: To assess the current evidence from recent clinical trials
      investigating antithrombotic agents for the prophylaxis and treatment of venous
      thromboembolism in cancer patients and for the effects of these agents on cancer
      progression. RECENT FINDINGS: A growing body of evidence supports the preventive
      use of antithrombotic strategies in subgroups of cancer patients. Moreover, in
      the long-term management of deep venous thrombosis in cancer patients, low
      molecular-weight heparin seems to represent a valid alternative to vitamin K
      antagonists. Finally, several studies have claimed a direct anticancer activity
      and a positive impact on prognosis of some antithrombotic agents, eg, aspirin and
      low-molecular-weight heparin. SUMMARY: Although recent evidence suggests low
      molecular-weight heparin as a possible option in the management and prevention of
      venous thromboembolism in cancer patients, more evidence from large randomized,
      prospective, controlled trials is needed to determine the exact the magnitude of
      the risk-benefit ratio associated with its use. The promising results on the
      effects of antithrombotic agents in the prognosis of cancer patients deserve
      further evaluation to estimate the potential and the feasibility of this
      approach.

PMID- 15257020
TI  - Predicting the risk of recurrence of venous thromboembolism.
AB  - PURPOSE OF REVIEW: Although several clinical studies have investigated the
      effects of different treatment periods in subjects after a VTE event, the optimal
      duration of oral anticoagulation is still uncertain. Our review focused on
      studies that evaluated different risk factors that might be useful to stratify
      patients into categories at different risk for recurrence. RECENT FINDINGS: The
      presence of irreversible, persistent, or transient risk factors affects the risk
      of recurrence. The inherited and acquired thrombophilic conditions that are
      associated with an increased risk of VTE may also be responsible for an increased
      risk of recurrence. Although this is still a matter of debate for the more common
      alterations, it is accepted for antithrombin, protein C, protein S deficiency,
      homozygous factor V Leiden, double heterozygosity, and antiphospholipid syndrome.
      It has been shown that high factor VIII levels are associated to increased risk
      of VTE recurrence. The presence of cancer is one of the most important persistent
      factors associated with VTE. Several studies have recently shown that D-dimer
      levels measured during and especially after oral anticoagulation interruption in
      subjects with a previous VTE, carriers or not of congenital thrombophilia have a
      high NPV for recurrence. The relation between the persistence of residual venous
      thrombosis and the risk of VTE recurrence has been investigated in two recent
      studies and both concluded that the persistence of a residual venous thrombosis
      is an important risk factor for recurrent thromboembolism and that its assessment
      may help clinicians modify the duration of anticoagulation in patients with DVT.
      SUMMARY: Both the clinical aspects of the first VTE event and individual
      characteristics (such as associated diseases, inherited or acquired thrombophilic
      conditions, altered D-dimer results, or the presence of residual venous
      thrombosis) concur in determining the recurrence risk of each patient. Whether
      the evaluation of these risk factors may help to tailor the secondary prevention
      treatment in each patient should be assessed by specifically designed
      intervention studies.

PMID- 15257021
TI  - Recombinant activated factor VII for non-hemophiliac bleeding patients.
AB  - THE PURPOSE OF THIS REVIEW: The purpose of this review is to summarize the safety
      and efficacy of recombinant activated factor VII in diverse clinical settings
      based on recent published anecdotal experiences and early results from
      prospective trials. RECENT FINDINGS: Recombinant activated factor VII is
      increasingly being used for off-label treatment and prophylaxis of bleeding in
      non-hemophiliac patients. Case reports would suggest that recombinant activated
      factor VII is an efficacious and safe "universal hemostatic agent". To date,
      results of several randomized control trials investigating recombinant activated
      factor VII in non-hemophiliacs have been published as abstracts, supporting
      recombinant activated factor VII safety, but not its efficacy. SUMMARY: Until the
      results of additional prospective trials are available, clinicians, who manage
      patients with challenging hemostatic complications, and transfusion medicine
      specialists should collaborate to develop local policies for off-label
      utilization of recombinant activated factor VII.

PMID- 15257022
TI  - Bibliography. Current world literature. Hemostasis and thrombosis.

PMID- 15257023
TI  - Conceptual models to understand tissue stem cell organization.
AB  - PURPOSE OF REVIEW: Theoretic and, in particular, mathematic models can help
      biologists to select and design experiments, to highlight general principles, to
      discriminate similar and to link different phenomena, and to predict novel
      features. Specifically, they contribute to an understanding of latent mechanisms
      and crucial parameters of biologic processes. The following review gives an
      overview of recent developments in the field of hematopoietic tissue stem cell
      modeling. RECENT FINDINGS: A number of experimental findings on heterogeneity,
      flexibility, and plasticity of hematopoietic and other tissue stem cells are
      challenging the classic stem cell concept of a predefined intrinsic stem cell
      program. Self-organizing systems provide a more elegant and comprehensive
      alternative to explain experimental data. SUMMARY: Within the last few decades,
      modeling approaches in stem cell biology have evolved and now encompass a broad
      spectrum of phenomena, ranging from the cellular level to the tissue level. The
      application of theoretic models is currently suggesting that we abandon the
      classic assumption of a strict developmental hierarchy and understand stem cell
      organization as a dynamic, functional process. Such a perspective has
      implications for a prospective characterization of tissue stem cells (eg,
      regarding gene expression profiles and genetic regulation patterns).

PMID- 15257024
TI  - Wnt signaling in the stem cell niche.
AB  - PURPOSE OF REVIEW: All the cells present in the blood are derived from the
      hematopoietic stem cell (HSC). Because mature blood cells have a limited life
      span, HSCs must perpetuate themselves through self-renewal to maintain a
      functional hematopoietic compartment for the lifetime of an organism. This review
      focuses on studies that identify the Wnt signaling pathway as a mediator of HSC
      self-renewal and maintenance and analyzes its potential influence in context of
      the HSC niche. RECENT FINDINGS: The Wnt signaling pathway has emerged as a
      potential regulator of self-renewal for HSCs. Recent findings have demonstrated
      that Wnt signaling can directly promote HSC self-renewal and ability to
      reconstitute the hematopoietic system of lethally irradiated mice. The recent
      findings that osteoblasts are an important regulatory component of the HSC
      microenvironment, and that elements of the Wnt signaling pathway can influence
      osteoblast frequency, raise the possibility that Wnt signaling may influence HSC
      function indirectly through the niche as well. SUMMARY: In this review, the
      authors evaluate the experimental evidence for a direct role of Wnt signaling
      HSCs as well as an indirect role through its influence on the HSC niche. Defining
      the mechanism of action of Wnt signaling in HSC maintenance in context of the
      surrounding microenvironment and determining how this signal may integrate with
      other niche derived signals represents the next challenge HSC biology.

PMID- 15257025
TI  - Signal processing underlying extrinsic control of stem cell fate.
AB  - PURPOSE OF REVIEW: Strategies to manipulate stem cells for therapeutic
      applications are limited by our inability to control or predict stem cell fate
      decisions in response to exogenous stimuli. This review focuses on the mechanisms
      by which exogenous stimuli influence cell fate. RECENT FINDINGS: Limitations in
      our ability to control cell fate arises from our primarily qualitative
      understanding of stem cell regulation, which proposes straightforward cue-fate
      relationships that appear to be the exception rather than the rule.
      Alternatively, consideration of the underlying quantitative, temporal, and
      spatial mechanisms governing extrinsic regulation of stem cell fate may enable
      novel approaches to control stem cell output predictively. SUMMARY: The authors
      review advances in the understanding of these underlying mechanisms, and discuss
      experimental and analytic tools necessary to investigate and use these mechanisms
      to control stem cell fate.

PMID- 15257026
TI  - Transplantable stem cells: home to specific niches.
AB  - PURPOSE OF REVIEW: Although the concept of engraftment and clinical
      reconstitution of the bone marrow was described several decades ago, the analysis
      of individual steps within this process remains a major focus of much current
      research in stem cell biology. In particular, this extends to the identification
      and characterization of the specific stem cell niche first proposed by Schofield
      in 1978. It is appropriate, therefore, that on the 25th anniversary of this
      publication, that we review recent progress in our understanding of the location
      and composition of the bone marrow stem cell niche and of the mechanisms involved
      in the initial phases of hematopoietic stem cell engraftment. RECENT FINDINGS:
      During the past 12 months there have been significant advancements in our
      understanding of the interplay of molecules involved in the homing of
      hematopoietic stem cells to the bone marrow. In addition, innovative
      methodologies have become available for the visualization of hematopoietic stem
      cells within the bone marrow in situ. In an important development in this area,
      studies our now focusing on events after transendothelial migration into the
      marrow cords, including mechanisms involved in hematopoietic stem cell migration
      to and lodgment within the hematopoietic stem cell niche. Furthermore, there have
      been numerous new reports analyzing the molecular regulation of hematopoietic
      stem cells within the bone marrow niche in situ. SUMMARY: Overall, recent
      advancements in our understanding of hematopoietic stem cell biology and, in
      particular, the interaction of hematopoietic stem cells with the hematopoietic
      microenvironment paves the way for expanded use in regenerative medicine.

PMID- 15257027
TI  - Recent advances in defining the hematopoietic stem cell niche.
AB  - PURPOSE OF REVIEW: Hematopoietic stem cells are thought to reside in discrete
      cellular spaces termed "niches." The cellular elements and matrix surrounding the
      stem cell within the niche constitute the microenvironment. The purpose of this
      review is to discuss recent reports that have begun to elucidate the geographic
      location, key cellular type, and molecular mechanisms operating in stem cell
      niches. RECENT FINDINGS: Studies that have revealed the osteoblast as the key in
      vivo cellular element of the adult stem cell niche are the most significant
      recent findings. Additional studies have highlighted the importance of the Notch
      and Wingless (Wnt) signaling pathways in the hematopoietic microenvironment.
      Genomewide expression screens have been used to perform molecular profiling of
      stromal cell lines that serve as surrogate stem cell niches. These profiles have
      revealed novel regulatory molecules and have reinforced the roles of classic
      developmental morphogens in the niche space. The transcriptional profiling from
      these screens suggests that it is highly unlikely that a single factor or signal
      transduction pathway will control stem cell properties. SUMMARY: This review
      highlights the recent advances made toward elucidating the cellular and molecular
      attributes of the hematopoietic stem cell niche. Complete knowledge of the
      cellular architecture and molecular mechanisms in stem cell niches is essential
      to understanding the basic stem cell behaviors of self-renewal and
      differentiation.

PMID- 15257028
TI  - Bibliography. Current world literature. Hematopoiesis.

PMID- 15257029
TI  - Bibliography. Current references for hematopoiesis.

PMID- 15257030
TI  - Immunobiology of natural killer lymphocytes in transplantation.
AB  - Natural killer (NK) lymphocytes are powerful effector cells of the peripheral
      immune system. NK cell functions are controlled by the expression of a variety of
      cell surface receptors with either inhibitory or activating roles. The genetic
      and functional diversity of this repertoire of receptors and the role of human
      leukocyte antigen class I histocompatibility molecules as a major group of NK
      receptor ligands endows NK cells with an innate alloreactive capacity. Early
      studies of experimental bone marrow transplantation revealed an important role
      for NK cells in the rejection of allogeneic grafts and contributed significantly
      to our understanding of NK cell behavior. Both animal models and in vitro studies
      have since implicated NK cells as contributors to the pathology of clinical
      transplantation. However, recent clinical studies have demonstrated the potential
      benefits of exploiting NK cell alloreactivity in mismatched hematopoietic stem
      cell transplantation for particular types of acute leukemia. Future
      investigations of NK cell alloreactive functions will undoubtedly reveal
      additional roles and potential therapeutic applications of this fundamental cell
      type in clinical transplantation.

PMID- 15257031
TI  - FK778: a powerful immunosuppressive, but will it really be good for you?

PMID- 15257032
TI  - The effects of FK778 in combination with tacrolimus and steroids: a phase II
      multicenter study in renal transplant patients.
AB  - BACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection,
      modifies vasculopathy, and shows anti-viral activity. We report first efficacy
      and safety data of FK778 in human kidney transplant recipients at two
      concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients
      were randomized to a 12-week treatment with FK778 in combination with tacrolimus
      (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received
      2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level
      group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received
      placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200
      microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of
      biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L,
      targeted plasma trough levels were reached by Day 3; in half of the patients in
      group H, the targeted levels were reached by Day 9. Graft survival at week 16 was
      89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1%
      for groups H, L, and P. For the subgroup of patients in which target levels were
      reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia,
      the most frequently reported adverse event especially in group H, was reversible.
      Mean total cholesterol and LDL-cholesterol levels were reduced during FK778
      treatment compared with group P. CONCLUSION: FK778 is pharmacologically active,
      well-tolerated, and safe. To fully benefit from this promising new drug, FK778
      dosing will be optimized in subsequent studies.

PMID- 15257033
TI  - alpha1,3-Galactosyltransferase gene-knockout miniature swine produce natural
      cytotoxic anti-Gal antibodies.
AB  - BACKGROUND: The expression of galactose alpha 1,3 galactose (Gal) in pigs has
      proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal pigs)
      have been produced by nuclear transfer/embryo transfer. METHODS: The tissues of
      five Gal pigs of SLA dd haplotype (SLA) were tested for the presence of Gal
      epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were
      tested by flow cytometry for binding of IgM and IgG to peripheral blood
      mononuclear cells (PBMC) from wild-type (Gal) SLA-matched pigs; serum
      cytotoxicity was also assessed. The cellular responses of PBMC from Gal swine
      toward Gal SLA-matched PBMC were tested by mixed leukocyte reaction and cell
      mediated lympholysis assays. RESULTS: None of the tissues tested showed Gal
      expression. Sera from all five Gal pigs manifested IgM binding to Gal pig PBMC,
      and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal
      cells could be demonstrated, which was lost after treatment of the sera with
      dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal
      swine had no proliferative or cytolytic T-cell response toward Gal SLA-matched
      PBMC. CONCLUSIONS: Gal pigs do not express Gal epitopes and develop anti-Gal
      antibodies that are cytotoxic to Gal pig cells. The absence of an in vitro
      cellular immune response between Gal and Gal pigs is related to their identical
      SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell
      responses. The model of Gal organ transplantation into a Gal SLA-matched
      recipient would be a valuable large animal model in the study of accommodation or
      B-cell tolerance.

PMID- 15257034
TI  - MDR-1 C3435T polymorphism influences cyclosporine a dose requirement in liver
      transplant recipients.
AB  - BACKGROUND: Cyclosporine A (CsA) is characterized by high interindividual
      variations in oral bioavailability and a narrow therapeutic index. CsA is a
      substrate for P-glycoprotein, a member of the ABC transporter family encoded by
      the multiple drug-resistant gene MDR1. METHODS: Because MDR1 gene exon 26 C3435T
      polymorphism influences intestinal P-glycoprotein expression, we investigated
      whether this polymorphism was correlated with variation in CsA dose requirement
      and concentration/dose ratio in 44 liver-transplant recipients during 1 month
      after transplantation. CsA concentration was measured 2 hours after
      administration (C2), according to international recommendations. RESULTS: The MDR
      1 wild-type genotype (3435CC) was observed in 15 patients (34%), whereas 21 (48%)
      patients were heterozygous (3435CT), and 8 (18%) patients were homozygous for the
      mutation (3435TT). There was no significant difference between the three groups
      regarding corticosteroids treatment or renal function during this period. One to
      3 days after liver transplantation, when every patient received a similar CsA
      weight-adjusted dose, the concentration/dose ratio was correlated with exon 26
      single nucleotide polymorphism and was significantly higher in subjects
      homozygous for the mutation (P=0.012). This was confirmed 1 month after
      transplantation (P=0.049), when the dose was adjusted to maintain the C2 target
      level of 1,000 microg/L and we observed that TT patients required approximately
      50% lower weight-adjusted CsA dose than wild-type patients (P=0,033).
      CONCLUSIONS: These findings demonstrate that the MDR1 exon 26 C3435T polymorphism
      is a major determinant of CsA concentration/dose ratio in liver-transplant
      recipients and is predictive of the dose of CsA to be administered to achieve the
      target C(2) concentration.

PMID- 15257035
TI  - Adiponectin and risk of new-onset diabetes mellitus after kidney transplantation.
AB  - BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a severe
      complication of kidney transplantation (KTx) with negative effects upon patient
      and graft survival. Several risk factors for NODAT have been described; however,
      the search for an early predictive marker is ongoing. It has recently been
      demonstrated that high concentrations of adiponectin (APN), which is an adipocyte
      derived peptide with antiinflammatory and insulin-sensitizing properties, protect
      against future development of type 2 diabetes in healthy individuals. The purpose
      of this report was to study pretransplant insulin resistance and analyze
      pretransplant serum leptin and APN levels as independent risk factors for the
      development of NODAT. METHODS: A total of 68 KTx patients were studied [mean age,
      48 +/- 11 years; 70% males; body mass index (BMI), 25 +/- 3 kg/m]; 31 KTx
      patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar
      age, sex, BMI, immunosuppression, and posttransplant time were studied. All
      patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25%
      cyclosporine A), and 76% of patients received mycophenolate mofetil. Family
      history of diabetes mellitus was recorded. Pretransplant homeostasis model
      assessment for insulin resistance (HOMA-IR) index was calculated from fasting
      plasma glucose and insulin. Pretransplant serum leptin and APN levels were
      determined by radioimmunoassay. RESULTS: NODAT patients showed higher
      pretransplant plasma insulin concentrations [NODAT, 13.4 (11-22.7) microIU/mL;
      non-NODAT, 10.05 (7.45-18.4) microIU/mL; P=0.049], HOMA-IR index [NODAT, 4.18
      (2.49-5.75); non-NODAT, 2.63 (1.52-4.68); P=0.043], and lower pretransplant serum
      APN concentration [NODAT, 8.78 (7.2-11.38) microg/mL; non-NODAT, 11.4 (8.56
      15.27) microg/mL, P=0.012]. Inverse correlations between APN and BMI (r=-0.33;
      P=0.014) and APN and HOMA-IR index (r=-0.39; P=0.002) and between APN and NODAT
      (r=-0.31; P=0.011) were observed. Multiple logistic regression analysis showed
      the patients with lower pretransplant APN concentrations to be those at greater
      risk of developing NODAT [Odds Ratio=0.832 (0.71-0.96); P=0.01]. CONCLUSION:
      Pretransplant serum APN concentration is an independent predictive factor for
      NODAT development in kidney-transplanted patients.

PMID- 15257036
TI  - Organ-specific T cell receptor repertoire in target organs of murine graft-versus
      host after transplantation across minor histocompatibility antigen barriers.
AB  - BACKGROUND: Minor histocompatibility antigens (miHags) are recognized by
      alloreactive cytotoxic donor T lymphocytes and trigger potent immune reactions
      such as graft-versus-host disease (GvHD) after major histocompatibility complex
      matched transplantation. Our study focuses on tissue-specific T-cell responses to
      miHag-encoded peptides in GvHD target organs during the first 30 days in a murine
      transplant model. METHODS: Complementarity determining region (CDR)3-size
      spectratyping was used to study T cell receptor (TCR) repertoires in recipient
      skin, liver, ileum, colon, spleen, and heart. RESULTS: GvHD occurred as early as
      day 14 and was proven by histology in skin, liver, ileum, and colon. The heart
      was histologically not affected by GvHD but showed endomyocardial "quilty
      lesions." Two distinct patterns of TCR diversities could be identified. In skin,
      a restricted V beta usage in combination with all J beta segments contrasted with
      a complete V beta repertoire in intestinal organs combined with a restricted J
      beta usage. Interestingly, TCR repertoire in the heart was almost identical with
      intestinal CDR3-size patterns. Persisting clones were found in skin from day 9 to
      30. In intestine and heart, identical sequences were obtained from several organs
      on day 14 and 21, but no persistence of CDR3 sequences could be observed.
      CONCLUSIONS: These results suggest that in the skin a limited number of
      persisting T cell clones maintains GvHD, whereas in the intestine, temporary
      expansions of different clones may fuel the process of GvHD. Strategies that
      eliminate tissue-specific T cells on the basis of their activational status
      rather than their V beta expression but at the same time preserve a broad,
      overall TCR repertoire will help to increase the efficacy and safety of
      allogeneic stem cell transplantation.

PMID- 15257037
TI  - Epstein-Barr virus latent membrane protein 1 activates nuclear factor-kappa B in
      human endothelial cells and inhibits apoptosis.
AB  - BACKGROUND: Although vascular changes and transplant vasculopathy have been
      described with cytomegalovirus, the impact of Epstein-Barr virus (EBV) on the
      vascular endothelium of the transplanted allograft is largely unknown. We
      recently reported that EBV (+) patients taken off immunosuppressive medications
      for periods of time had a low incidence of chronic rejection. In another report,
      we noted that there was expression of the "protective" antiapoptotic factor Bcl-2
      in the vascular endothelium of transplant allografts from EBV (+) patients. In
      this report, we determined the effect of latent EBV infection on endothelial cell
      activation and apoptosis. METHODS: Cultured human umbilical vein endothelial
      cells (HUVEC) were either infected with EBV or transduced with EBV latent
      membrane protein 1 and examined for apoptosis, nuclear factor (NF)-kappaB
      activation, and expression of chemokines, cytokines, and adhesion molecules.
      RESULTS: EBV infection and latent membrane protein 1 expression in HUVEC resulted
      in NF-kappaB activation and increased expression of the cytokines interleukin
      (IL)-1alpha, IL-1beta, and IL-6; the chemokines IL-8, monocyte chemotactic
      protein-1, and RANTES; and the adhesion molecules intercellular adhesion molecule
      1, vascular cell adhesion molecule-1, and E-selectin. There was increased
      expression of the antiapoptotic genes A1, c-IAP2, and TRAF1; inhibition of
      caspase 3; and protection from apoptosis. CONCLUSIONS: Latent EBV in HUVEC
      results in constitutive NF-kappaB activation, protection from apoptosis, and
      increased basal expression of inflammatory factors. The in vivo effect of latent
      EBV in the vascular endothelium of the transplanted allograft and its resultant
      impact on transplant vasculopathy are the subject of further investigations in
      our laboratory.

PMID- 15257038
TI  - A role for CD2 antibodies (BTI-322 and its humanized form) in the in vivo
      elimination of human T lymphocytes infiltrating an allogeneic human skin graft in
      SCID mice: an Fcgamma receptor-related mechanism involving co-injected human NK
      cells.
AB  - BACKGROUND: Pilot clinical studies have shown that the rat anti-human-CD2
      monoclonal antibody, LoCD2a/BTI-322, can efficiently prevent and treat acute
      kidney rejection. However, the in vivo mechanism by which it prevents allograft
      rejection has not been studied. BTI-322 and its humanized form have been shown to
      mediate in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) against CD2
      cells through the activation of monocytes or natural killer (NK) cells. METHODS:
      Human fetal skin samples were grafted into severe combined
      immunodeficient/nonobese diabetic mice. Five weeks later (day 0), the mice were
      injected with human allogeneic peripheral blood lymphocytes (PBL). Either on day
      0 or on day 14, mice were treated with BTI-322, hu-BTI-322, or their F(ab')2
      fragments. Peripheral blood mononuclear cells (PBMC) thoroughly devoid of NK
      cells were also assayed. RESULTS: After injection of PBL, the human skins became
      heavily infiltrated with activated human T lymphocytes, resulting in dermal
      microvascular injuries indicative of graft rejection. Early treatment with BTI
      322 and hu-BTI-322 prevented all these events. These CD2 antibodies rapidly
      eliminated human T lymphocytes that had already infiltrated the grafts, with no
      evidence of recirculation toward the spleen. Their F(ab')2 fragments were, in
      contrast, ineffective. Elimination of NK cells from injected PBMC prevented the
      curative effect exerted by whole CD2 antibodies. It also abrogated their
      cytotoxicity potential against CD2 cells in ADCC assays. CONCLUSION: F(ab')2
      fragments of the CD2 antibodies could not prevent allograft rejection, whereas
      whole immunoglobulin G could, and human NK cells were required for the curative
      effect exerted by these antibodies. The results are consistent with an FcgammaR
      dependent ADCC mechanism mediated in vivo by human NK cells.

PMID- 15257039
TI  - Development of donor-specific immunoregulatory T-cells after local CTLA4Ig gene
      transfer to pancreatic allograft.
AB  - BACKGROUND: CTLA4Ig gene transfer directly to graft tissue might have the
      potential to avoid the need for systemic immunosuppression. In our previous
      studies of bio-breeding (BB) rats, local adenovirus-mediated CTLA4Ig gene
      transfer protected the pancreas from autoimmune and alloimmune responses. This
      study investigated the potency of local CD28/B7 costimulatory blockade for
      induction of donor-specific tolerance and further examined the existing
      mechanisms. METHODS: Brown Norway (BN; RT1)-pancreaticoduodenal grafts
      transfected with Ad.CTLA4Ig via intraarterial ex vivo perfusion were transplanted
      into streptozotocin-induced diabetic Lewis (LEW; RT1) rats. RESULTS: Ad.CTLA4Ig
      transduced grafts combined with a short course of FK506 resulted in indefinitely
      prolonged survival (>156 days vs. 19.5 days with FK506 alone). CTLA4Ig was
      predominantly expressed in grafts on day 4. The expression was gradually
      diminished and was only slightly detectable at day >100. The proliferative
      responses against BN antigen were remarkably enhanced among recipients with
      rejected grafts, but the T-cells from tolerant recipients (>100 days) showed poor
      cytotoxic responses. On adoptive transfer assay, the splenic T-cells of tolerant
      recipients were able to suppress the rejection of BN, but not third-party Wistar
      Furth (WF; RT1) hearts in irradiated (480 cGy) LEW recipients. The percentage of
      CD4CD25 splenic T-cells was significantly increased in tolerant recipients (13.53
      +/- 4.06% vs. 6.06 +/- 0.56% in naive rats). CONCLUSION: CTLA4Ig gene transfer to
      the pancreaticoduodenal allograft combined with a short course of FK506 induces
      donor-specific tolerance. The mechanism of maintaining tolerance could be
      explained by development of splenic T suppressor cells.

PMID- 15257040
TI  - Description of B lymphocytes and plasma cells, complement, and
      chemokines/receptors in acute liver allograft rejection.
AB  - BACKGROUND: Although antibody mechanisms play a pathogenetic role in liver
      allograft rejection, no data exist on B lymphocytes, plasma cells, complement,
      and chemokines in rejected liver tissue. METHODS: Liver biopsy specimens from 25
      patients with acute allograft rejection (AR) (rejection activity index, RAI
      score: 1-9) were analyzed by immunohistochemistry (IH) and reverse transcriptase
      polymerase chain reaction (RT-PCR) and compared with biopsy specimens taken prior
      to implantation (PI). The number of CD20 and CD138 cells was evaluated, and the
      presence and abundance of the chemokines macrophage inflammatory protein (MIP)
      3alpha, CXCL9, CXCL10, CXCL11, CXCL12, and their receptors CCR-6, CXCR3, and
      CXCR4 were examined. Complement depositions were visualized by C4d IH. RESULTS:
      The numbers of B lymphocytes (P=0.002) and plasma cells (P=0.022) were
      significantly higher in AR biopsy specimens compared with PI biopsy specimens.
      MIP-3alpha and CCR-6 cells were detected in the portal fields of all AR biopsy
      specimens. IH double staining revealed a colocalization of MIP-3alpha/CD20 cells;
      C4d deposits could be demonstrated along the portal capillaries. All examined
      chemokines and receptors could be detected in normal liver tissue and in AR
      biopsy specimens by RT-PCR and semiquantitative RT-PCR, demonstrating an
      overexpression of CXCL10 and -11. CONCLUSIONS: The significant increase of B
      lymphocytes and plasma cells during acute rejection, together with the lack of a
      significant increase of proliferating cells, indicates that the migration of B
      lymphocytes and plasma cells-promoted by the expression of B-cell activating
      chemokines/receptors-plays a key role in acute liver rejection. The C4d deposits
      along the portal capillaries indicate a humorally mediated alloresponse caused by
      the accumulated B and plasma cells.

PMID- 15257041
TI  - FK778 attenuates lymphocyte-endothelium interaction after cardiac
      transplantation: in vivo and in vitro studies.
AB  - BACKGROUND: The malononitrilamide FK778 is a novel derivate of leflunomide and
      interacts with T- and B-cell function by inhibiting de novo pyrimidine synthesis.
      We investigated the effects of FK778 upon acute cardiac allograft rejection and
      upon adhesion molecule upregulation in experimental transplantation and by using
      in vitro cell culture. METHODS: Heterotopic, abdominal cardiac transplantations
      were performed in the Brown Norway (BN) to Lewis (Lew) rat model. The study
      groups received daily low- or high-dose FK778 immunosuppression. FK778 plasma
      levels were quantified by HPLC. Grafts were harvested on the fifth postoperative
      day for histologic and immunohistologic examinations using computerized
      morphometry. Purified BN aortic endothelial cell cultures were pretreated with
      low- or high-dose FK778 according to FK778 plasma levels and were stimulated with
      tumor necrosis factor (TNF)-alpha. Adhesion molecule expression was quantified by
      immunofluorescence, FACS analysis, and Western blotting. Lymphocyte-endothelium
      adhesion assays were performed using purified Lew lymphocytes and radiolabeled
      TNF-alpha was used for receptor binding assays. RESULTS: FK778 treatment dose
      dependently reduced graft mononuclear infiltration of CD4(+), CD8(+), and ED1(+)
      cells, but only high-dose FK778 treatment significantly reduced early
      upregulation of ICAM-1 and VCAM-1 in vivo. FK778 also dose-dependently reduced
      TNF-alpha-stimulated endothelial adhesion molecule upregulation in vitro, whereas
      the effect on VCAM-1 was more dominant. We did not find evidence that FK778
      interferes with surface receptor binding of TNF-alpha. Lymphocyte adhesion to
      endothelial cell monolayers was significantly attenuated by FK778. CONCLUSION:
      Besides its inhibitory effect on pyrimidine synthesis, FK778 directly reduces
      endothelial adhesion molecule upregulation and attenuates lymphocyte-endothelium
      interaction, which is a critical step in graft rejection.

PMID- 15257042
TI  - Objective and rapid assessment of pancreas graft viability using 31P-nuclear
      magnetic resonance spectroscopy combined with two- layer cold storage method.
AB  - BACKGROUND: With the current shortage of donors, there is a critical need to
      optimally use "less-than-ideal" donors for pancreas transplantation. Objective
      and rapid means for assessing graft viability and suitability for transplantation
      are mandatory. This study examined the possibility of graft viability assessment
      and posttransplant outcome prediction using (31)P-nuclear magnetic resonance
      (NMR) spectroscopy combined with the two-layer cold-storage method (TLM).
      METHODS: Canine pancreas grafts were preserved with TLM for 24 hours after 0, 60,
      or 120 minutes of warm ischemia (groups 1, 2, or 3, respectively). After
      preservation, we determined intragraft phosphate metabolites noninvasively using
      (31)P-NMR spectroscopy. Time required for this assessment was 5 minutes. Because
      our previous studies demonstrated that all grafts in groups 1 and 2 were
      successfully transplanted (the viable group), whereas all in group 3 failed to
      survive (the nonviable group), the possibility of posttransplant outcome
      prediction was examined on the basis of the comparison between these two groups.
      RESULTS: The ratios of inorganic phosphate/gamma-adenosine triphosphate (Pi/gamma
      ATP) and Pi/beta-ATP reflected the extent of graft damage, and the differences
      were statistically significant among groups 1, 2, and 3. On the basis of analyses
      of receiver operator characteristic curves, the optimum cutoff levels between the
      viable and nonviable groups were 1.6 and 2.2 for Pi/gammaATP and Pi/betaATP,
      respectively. The accuracy rates of these ratios were both 83%. CONCLUSION: (31)P
      NMR spectroscopy combined with TLM preservation could provide an objective,
      rapid, and possibly noninvasive means to assess pancreas graft viability and to
      determine suitability of damaged pancreata for organ transplantation.

PMID- 15257043
TI  - Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon
      tetrachloride-induced liver fibrosis in mice.
AB  - BACKGROUND: Fibrosis is the common end stage of most liver diseases, for which,
      unfortunately, there is no effective treatment available currently. It has been
      shown that mesenchymal stem cells (MSCs) from bone marrow (BM) could engraft in
      the lung after bleomycin exposure and ameliorate its fibrotic effects. This study
      was designed to evaluate the effect of Flk1 MSCs from murine BM (termed here Flk1
      mMSCs) on fibrosis formation induced by carbon tetrachloride (CCl4). METHODS: A
      CCl(4)-induced hepatic fibrosis model was used. Flk1 mMSCs were systemically
      infused immediately or 1 week after mice were challenged with CCl(4). Control
      mice received only saline infusion. Fibrosis index and donor-cell engraftment
      were assessed 2 or 5 weeks after CCl(4) challenge. RESULTS: We found that Flk1
      mMSCs transplantation immediately, but not 1 week after exposure to CCl(4),
      significantly reduced CCl(4)-induced liver damage and collagen deposition. In
      addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice
      receiving immediate Flk1 mMSCs transplantation after CCl(4) challenge were
      significantly lower compared with those of control mice. More importantly,
      histologic examination suggested that hepatic damage recovery was much better in
      these immediately Flk1 mMSCs-treated mice. Immunofluorescence, polymerase chain
      reaction, and fluorescence in situ hybridization analysis revealed that donor
      cells engrafted into host liver, had epithelium-like morphology, and expressed
      albumin, although at low frequency. CONCLUSION: These results suggest that Flk1
      mMSCs might initiate endogenous hepatic tissue regeneration, engraft into host
      liver in response to CCl(4) injury, and ameliorate its fibrogenic effects.

PMID- 15257044
TI  - Assessment of optimal size and composition of the U.S. National Registry of
      hematopoietic stem cell donors.
AB  - BACKGROUND: The National Marrow Donor Program (NMDP) receives federal funding to
      operate a registry of over 4 million volunteer donors for patients in need of a
      hematopoietic stem cell transplant. Because minority patients are less likely to
      find a suitably matched donor than whites, special efforts have been aimed toward
      recruitment of minorities. Significant financial resources are required to
      recruit and tissue type additional volunteer donors. METHODS: Population genetics
      models have been constructed to project likelihoods of finding a human leukocyte
      antigen (HLA)-matched donor for patients of various racial/ethnic groups. These
      projections have been made under a variety of strategies for expansion of the
      NMDP Registry. Cost-effectiveness calculations incorporated donor unavailability
      and other barriers to transplantation. RESULTS: At current recruitment rates, the
      probability of an available HLA-A,B,DRB1 matched donor is projected to increase
      from 27% to 34%; 45% to 54%; 75% to 79%; and 48% to 55%, for blacks,
      Asians/Pacific Islanders, whites and Hispanics, respectively, by the year 2007.
      Substantial increases in minority recruitment would have only modest impacts on
      these projections. These projections are heavily affected by donor availability
      rates, which are less than 50% for minority volunteers. CONCLUSIONS: Continued
      recruitment of additional volunteers can improve the likelihood of finding an HLA
      matched donor, but will still leave significant numbers of patients of all
      racial/ethnic groups without a match. Efforts to improve donor availability
      (especially among minorities) and to increase the number of patients with access
      to the NMDP Registry may prove to be more cost-effective means of increasing
      transplants.

PMID- 15257045
TI  - Influence of pancreas preservation on human islet isolation outcomes: impact of
      the two-layer method.
AB  - BACKGROUND: Human pancreas preservation for islet transplantation holds
      additional challenges and considerations compared with whole pancreas
      transplantation. The purpose of this study was to clarify the limitations of the
      University of Wisconsin (UW) solution and the potentials of the two-layer method
      (TLM) for pancreas preservation before human islet isolation. METHODS: We
      retrospectively evaluated human islet isolation records between January 2001 and
      February 2003. One hundred forty-two human pancreata were procured from cadaveric
      donors and preserved by means of the UW solution (n=112) or TLM (n=30). Human
      islet isolations were performed using a standard protocol and assessed by islet
      recovery and in vitro function of islets. RESULTS: Eight to ten hours of cold
      ischemia in the UW solution is a critical point for successful islet isolations.
      It is difficult to recover a sufficient number of viable islets for
      transplantation from human pancreata with more than 10 hours of cold storage in
      the UW solution. The overall islet recovery in the TLM group was significantly
      higher than in the UW group. With 10 to 16 hours of cold storage, the success
      rates of islet isolations remained at 62% in the TLM group but decreased to 22%
      in the UW group. Transplanted islets in the TLM group worked well in the
      recipients. CONCLUSIONS: There are time limitations for using the UW solution for
      pancreas preservation before human islet isolation. The TLM is a potential method
      to prolong the optimal cold storage time for successful islet isolations.

PMID- 15257046
TI  - No important influence of limited steroid exposure on bone mass during the first
      year after renal transplantation: a prospective, randomized, multicenter study.
AB  - BACKGROUND: Steroid-related bone loss is a recognized complication after renal
      transplantation. In a prospective, randomized, multicenter study we compared the
      influence of a steroid-free immunosuppressive regimen with a regimen with limited
      steroid exposure on the changes in bone mass after renal transplantation.
      METHODS: A total of 364 recipients of a renal transplant were randomized to
      receive either daclizumab (1 mg/kg on days 0 and 10 after transplantation;
      steroid-free group n=186) or prednisone (0.3 mg/kg per day tapered to 0 mg at
      week 16 after transplantation; steroids group n=178). All patients received
      tacrolimus, mycophenolate mofetil, and, during the first 3 days, 100 mg
      prednisolone intravenously. Changes in bone mineral density (BMD) were evaluated
      in 135 and 126 patients in the steroid-free and steroids group, respectively.
      RESULTS: The mean (+/- SD) BMD of the lumbar spine decreased slightly in both
      groups during the first 3 months after transplantation (steroid-free -1.3 +/-
      4.0% [P<0.01]; steroids -2.3 +/-4.2% [P<0.01]). In the following months, lumbar
      BMD recovered in both groups (P<0.01), resulting in a lumbar BMD at 12 months
      after transplantation comparable with the baseline value. No difference between
      the groups was found at 3 months (steroid-free versus steroids +1.0%; 95%
      confidence interval -0.0%-+2.0%, P=0.060) and at 12 months after transplantation
      (steroid-free versus steroids +0.9%; 95% confidence interval -0.8%-+2.6%, NS).
      CONCLUSION: The use of a moderate dose of steroids during 4 months after
      transplantation has no important influence on bone mass during the first year
      after renal transplantation. On average, both regimens prevented accelerated bone
      loss.

PMID- 15257047
TI  - Early growth responsive gene (Egr)-1 expression correlates with cardiac allograft
      rejection.
AB  - BACKGROUND: Early growth response factor (Egr)-1 is a transcription factor
      induced by inflammatory cytokines that regulates the expression of cytokines,
      adhesion molecules, other genes pertinent to inflammatory, and proliferative
      pathologies. Its expression in allografted tissue and role in the pathogenesis of
      graft rejection has not been explored. The goal of this work is to determine
      whether Egr-1 expression could be used as a surrogate marker of cardiac allograft
      rejection. METHODS: Egr-1 protein expression was analyzed in endomyocardial
      biopsies of different rejection grades by immunohistochemistry. Egr-1 mRNA
      expression was analyzed in 106 biopsies from 11 transplant patients by
      semiquantitative reverse-transcriptase polymerase chain reaction. Egr-1 was also
      analyzed in coronary arteries from patients with coronary artery vasculopathy
      (CAV) by Western blot and immunohistochemistry. RESULTS: No expression of Egr-1
      protein was observed in grade 0 biopsies by immunohistochemistry. Strong nuclear
      Egr-1 was noted in leukocytes and cardiac myocytes in grade 3 biopsies. A clear
      pattern emerged where 20% (6/30), 34% (20/58), 22% (2/9), and 89%(8/9) of
      International Society For Heart and Lung Transplantation grade 0, 1, 2, and 3
      biopsies were positive for Egr-1 mRNA. There was a significant (P<0.005)
      relationship between Egr-1 mRNA expression and rejection grade in endomyocardial
      biopsies. The calculated odds ratio indicates that a biopsy has a 2.18% greater
      probability of Egr-1 expression per increasing grade of rejection. Egr-1 was also
      up-regulated in vascular cells in coronary arteries from patients with CAV.
      CONCLUSIONS: In consideration of its role as a transcription factor for genes
      involved in pathologic processes, Egr-1 expression in endomyocardial biopsies may
      act as a surrogate marker of cardiac allograft rejection.

PMID- 15257048
TI  - Liver transplantation does not prevent the development of life-threatening
      arrhythmia in familial amyloidotic polyneuropathy, Portuguese-type (ATTR
      Val30Met) patients.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is today the only available
      treatment to halt the progress of familial amyloidotic polyneuropathy (FAP).
      Because heart arrhythmia and conduction disturbances are well-known
      manifestations of FAP, the aim of this study was to investigate the occurrence
      and development of heart conduction and rhythm disturbances in Swedish FAP
      patients who underwent liver transplantation. METHODS: Ambulatory 24-hour
      electrocardiography (ECG) recordings (Holter-ECGs) were available from 30
      patients, who had been investigated before and reexamined after OLT. RESULTS.:
      The number of patients with abnormalities on their ECG recordings increased after
      OLT. Four patients developed serious arrhythmia after transplantation that
      necessitated the insertion of a pacemaker 40 months or longer after OLT.
      CONCLUSIONS: The development of cardiac conduction disturbances and arrhythmias
      appear not to be halted by liver transplantation, indicating that the physician
      should be aware of the potential risk for FAP patients receiving transplants to
      develop fatal arrhythmia. The follow-up after liver transplantation should
      include Holter-ECG recordings.

PMID- 15257049
TI  - Impaired kidney graft survival is associated with the TNF-alpha genotype.
AB  - BACKGROUND: The TNF2 allele at position -308 of the tumor necrosis factor (TNF)
      alpha gene is associated with high TNF production. The purpose was to study the
      association of this gene polymorphism with rejection episodes and graft survival
      after kidney transplantation. METHODS: A retrospective analysis of transplant
      outcomes of patients who only had been treated with one single form of
      immunosuppression consisting of cyclosporine, azathioprine, and prednisolon was
      performed. RESULTS: We found that 115 (73%) patients had the TNF1/TNF1 genotype,
      whereas 42 (27%) were TNF2 positive. There was no difference in the overall acute
      rejection frequency between these two groups (50% in each), but our data showed a
      non-significant tendency towards a higher frequency of steroid resistant
      rejections in the TNF2 positive group (57% vs. 40%). There was no significant
      difference in graft survival between the two genotype groups, although an early
      tendency towards worse survival was seen in TNF2 recipients. However, the TNF2
      positive recipients with rejection episodes had far worse graft survival compared
      with the TNF1/TNF1 recipients with rejection episodes (P<0.02). No difference was
      seen between the two genotype groups in patients without rejection episodes.
      CONCLUSION: Our data propose that potentially high TNF producers with the TNF2
      allele do not have an increased risk for rejection episodes, but if rejection
      episodes occur, they have a significantly increased risk for early graft loss.
      TNF production may intensify rejection, but is not a primary factor for the
      induction of such acute immune activation.

PMID- 15257050
TI  - Dose study of thymoglobulin during conditioning for unrelated donor allogeneic
      stem-cell transplantation.
AB  - BACKGROUND: Thymoglobulin given before allo-hematopoietic stem-cell
      transplantation (HSCT) from unrelated donors reduces acute graft-versus-host
      disease (GvHD), but the optimal dose is unknown. METHOD: Four different doses of
      Thymoglobulin were given to 162 patients with hematologic malignancies undergoing
      unrelated donor HSCT: 4, 6, 8, and 10 mg/kg. Stem-cell source was bone marrow in
      102 cases and peripheral blood stem cells in 60. Conditioning was
      cyclophosphamide combined with total-body irradiation or busulfan. GvHD
      prophylaxis was cyclosporine and methotrexate. RESULTS: The lowest dose of
      Thymoglobulin significantly increased the risk for acute GvHD II or greater (odds
      ratio [OR] 2.67, P=0.015) and III or greater (OR 4.12, P=0.03). GvHD-associated
      deaths were more common in the lowest Thymoglobulin dose (6/51) compared with
      higher doses (2/111), P<0.01. No difference in bacteremia and cytomegalovirus
      reactivation was found. A trend for more infectious death (11/55 vs. 11/107,
      P=0.09) was found in the 10 mg/kg group compared with lower doses. Median dose of
      Thymoglobulin (6-8 mg/kg) was associated with lower transplant-related mortality
      (TRM) (hazard ratio [HR] 0.35, P=0.03) and better survival (HR 0.45, P=0.027) in
      multivariate analysis, whereas no effect on relapse and relapse-free survival was
      found. CONCLUSION: Low-dose (4 mg/kg) of Thymoglobulin increased the risk for
      severe acute GvHD, whereas 10 mg/kg increased the risk for infectious death.
      Median doses (6-8 mg/kg) of Thymoglobulin resulted in the lowest TRM and best
      survival.

PMID- 15257051
TI  - Outcome and risk factors of de novo autoimmune hepatitis in living-donor liver
      transplantation.
AB  - BACKGROUND: Graft dysfunction mimicking autoimmune hepatitis (AIH) develops only
      rarely after liver transplantation for nonautoimmune liver disease. The long-term
      prognosis and risk factors of de novo AIH after living-donor liver
      transplantation (LDLT) are unknown. METHODS: We review our LDLT series to
      investigate the incidence and outcome of this form of graft dysfunction, focusing
      on follow-up histology. RESULTS: Of 633 patients who underwent LDLT at Kyoto
      University from 1990 to 2002, 13 (2.1%) developed graft dysfunction with
      interface hepatitis resembling AIH (2 males, 11 females). The median age at LDLT
      of these 13 patients was 10 years (8 months to 26 years). All received tacrolimus
      based immunosuppression. The dysfunction presented at a median interval of 3.1
      (0.7-9.5) years after LDLT. Nine had definite AIH, and four had probable AIH at
      the onset of hepatitis. Patients were followed after a median of 3.5 (0.1-8)
      years from the onset of de novo AIH. Of 11 patients who underwent follow-up
      histologic evaluation, 3 underwent retransplantation, and 8 continued to have
      similar findings on subsequent biopsies, with fluctuations in the amount of
      necroinflammatory activity and an increase in fibrosis despite treatment. In a
      multivariate analysis, acute rejection episodes and recipient age between 11 and
      15 years at LDLT independently had predictive value for the development of de
      novo AIH. Human leukocyte antigen-A, B, and DR mismatches and sex mismatch did
      not influence the occurrence of de novo AIH. CONCLUSION: This series highlights
      the more severe histologic outcome of de novo AIH with longer follow-up despite
      immunosuppressive treatment. De novo AIH may arise from alloimmunologic injury,
      marked by clinically obvious episodes of acute rejection.

PMID- 15257052
TI  - Five-year follow up of thymoglobulin versus ATGAM induction in adult renal
      transplantation.
AB  - BACKGROUND: One-year results of a randomized, double-blinded trial of
      Thymoglobulin versus Atgam for induction therapy in renal transplantation
      revealed that Thymoglobulin was associated with higher event-free survival (94%
      vs. 63%), less acute rejection (4% vs. 25%), and better graft survival. This
      article compares the safety and efficacy of Thymoglobulin versus Atgam induction
      through 5 years. METHODS: Review and analysis of clinic records and electronic
      databases. RESULTS: At 5 years, event-free survival (73% vs. 33%, P<0.001), graft
      survival (77% vs. 55%, P=0.047), and freedom from rejection (92% vs. 66%,
      P=0.007) were higher with Thymoglobulin versus Atgam. No additional
      cytomegalovirus (CMV) disease occurred after the first year with Thymoglobulin or
      Atgam (13% vs. 33%, P=0.056). There were two cases of posttransplant
      lymphoproliferative disorder (PTLD) with the Atgam arm and none with
      Thymoglobulin. Thymoglobulin was associated with profound lymphopenia at 2 years
      after transplantation. CONCLUSIONS: Thymoglobulin was associated with higher
      event-free survival, graft survival, and freedom from rejection without increased
      PTLD or CMV disease at 5 years compared with Atgam. The prolonged and profound
      lymphopenia may contribute to the long-term results associated with
      Thymoglobulin.

PMID- 15257053
TI  - Does donor brain death influence acute vascular rejection in the kidney
      transplant?
AB  - BACKGROUND: There is increasing experimental evidence to suggest that donor brain
      death enhances susceptibility to early inflammatory responses such as acute
      rejection in the kidney transplant. The aim of the present study was to establish
      whether the injury induced or aggravated by donor brain death could exert an
      effect on recipient immunologic tolerance by comparing data from patients
      receiving a kidney from non-heart-beating donors (NHBD) or from brain-dead donors
      (BDD). METHODS: We reviewed data corresponding to 372 renal transplants performed
      from January 1996 to May 2002. The data were stratified according to donor type
      as 197 (53%) brain-dead and 175 (47%) non-heart-beating donors, and the two
      groups were compared in terms of acute vascular rejection by Cox's regression
      analysis. RESULTS: The rate of vascular rejection was 28% in the BDD group and
      21.7% in the NHBD (P=0.10). The following predictive variables for acute vascular
      rejection were established: brain death [RR 1.77 (95% CI 1.06-3.18)], presence of
      delayed graft function [RR 3.33 (1.99-5.55)], previous transplant [RR 2.35 (1.34
      4.13)], recipient age under 60 years [RR 1.86 (0.99-2.28)], female recipient [RR
      1.50 (0.99-2.28)], cerebrovascular disease as cause of donor death [RR 1.72 (1.02
      2.91)], and triple therapy as immunosuppressive treatment. CONCLUSION: Donor
      brain death could be a risk factor for the development of vascular rejection in
      kidney recipients. This process could affect the quality of the graft and host
      alloresponsiveness. Delayed graft function in transplants from dead brain donors
      could be a reflection of severe autonomic storm, leading to a higher incidence of
      vascular rejection in these patients.

PMID- 15257055
TI  - Lung epithelial cells and type II pneumocytes of donor origin after allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: In the present investigation, we determined whether donor epithelial
      lung cells might be detected after allogeneic hematopoietic stem cell
      transplantation (HSCT). METHODS: Lung-tissue specimens were obtained at autopsy
      from four female patients, two with male donors, after nonmyeloablative HSCT.
      Immunohistochemical staining for cytokeratin was used to identify lung epithelial
      cells. The tissue sections were analyzed for the presence of donor-derived lung
      epithelial cells with the use of fluorescence in situ hybridization of XY
      positive cells. RESULTS: All patients showed almost complete donor chimerism in
      all cell lineages after HSCT with polymerase chain reaction of minisatellites. In
      the two positive controls, between 2% and 6% Y-chromosome-positive epithelial
      lung cells were detected in each section. Surfactant-positive male epithelial
      cells were also detected, indicating engraftment of type II pneumocytes. In the
      two negative controls, no Y-chromosome-positive cells were detected. CONCLUSION:
      Circulating donor stem cells may differentiate into lung epithelial cells after
      allogeneic HSCT.

PMID- 15257054
TI  - Hand-assisted retroperitoneoscopic live donor nephrectomy in comparison to open
      and laparoscopic procedures: a prospective study on donor morbidity and kidney
      function.
AB  - BACKGROUND: Living donor nephrectomy (LDN) is a unique surgical challenge where
      surgery is performed on a healthy individual. A new hand-assisted
      retroperitoneoscopic nephrectomy (HARS) technique was compared to transperitoneal
      laparoscopic nephrectomy (LAP) and open nephrectomy (OPEN). The aim was to
      examine the perioperative and postoperative morbidity, and the effects of the
      different surgical techniques with regard to renal function. METHODS: Donors
      (n=36) were divided into three groups (HARS, LAP and OPEN) according to surgical
      technique. During the operations, renal function, hormone output, warm ischemia
      time (WIT) and operating time were recorded. Renal function, complications,
      convalescence and allograft outcome were followed postoperatively for one year.
      RESULTS: OPEN and HARS groups showed similar operation times: 150 (95-218)
      minutes and 145 (124-225) minutes, respectively. LAP procedures took longer: 218
      (163-280) minutes. OPEN had the shortest WIT at 91 (55-315) seconds; LAP had the
      longest WIT at 207 (100-319) seconds, with HARS at 180 (85-240) seconds. In all
      groups, glomerular filtration rate and urine production were decreased during
      surgery. Endoscopic techniques had a higher catecholamine release, and OPEN
      donors showed higher serum aldosterone. Endoscopic techniques showed shorter
      convalescence and less postoperative pain compared to OPEN. HARS had a smaller
      rise in creatinine than LAP, and HARS recipients a better creatinine clearance
      than the other groups in the early posttransplantation period. CONCLUSIONS:
      Evaluation of HARS shows that the operation is quick, the donors experience
      little pain, and recovery time is short. The renal function for donors and
      recipients is somewhat favorable to open surgery and transperitoneal laparoscopic
      approaches.

PMID- 15257056
TI  - PX3.102, a novel chinese herb extract, diminishes chronic airway allograft
      rejection.
AB  - More effective immunosuppressants are needed to improve lung-transplantation
      survival. PX3.102 is a novel immunosuppressant isolated from a mixture of
      traditional Chinese herbs. We tested its protective role on chronic lung
      rejection in the heterotopic tracheal transplant model. C57BL/6 mice received
      BALB/c tracheal grafts and were treated with PX3.102, cyclosporine A, or vehicle.
      PX3.102 improved tracheal allograft lumen patency (*P<0.01 vs. vehicle and P=0.14
      vs. cyclosporine A) but not epithelialization (P>0.2 vs. vehicle). Subsequent in
      vitro studies demonstrated that PX3.10 was toxic to fully differentiated human
      tracheal epithelial cells in a dose-dependent manner. PX3.102 markedly suppressed
      antigen-specific lymphocyte proliferation in vitro at a concentration 10 times
      lower than cyclosporine A. In conclusion, PX3.102, a promising and potent
      immunosuppressant, although exhibiting toxicity to airway epithelial cells at
      high doses, is effective in inhibiting chronic airway allograft rejection.

PMID- 15257057
TI  - Impact of donor-recipient MHC matching on experimental islet allotransplant
      survival in naive and presensitized Lewis rats.
AB  - In human islet transplantation (ITX), the impact of donor-recipient major
      histocompatibility complex (MHC) matching on transplant survival is currently
      unknown. Utilizing defined MHC mismatches, we have investigated the outcome of
      ITX in naive and presensitized congenic Lewis rats. ITX into streptozotocin
      diabetic Lewis rats was performed under the kidney capsule. Presensitization by
      skin transplantation was performed on days 1, 28, and 56, followed by ITX on day
      84. Survival was greatest in isolated MHC class I mismatches, followed by
      isolated MHC class II mismatches. The shortest transplant survival was observed
      following full MHC mismatched ITX (P<0.05 vs. isolated MHC class I or II).
      Following recipient presensitization, islets in general showed reduced survival
      compared to naive recipients. In this congenic rat model, islet transplant
      survival was significantly influenced by the degree of donor-recipient MHC
      matching, as well as by recipient presensitization. These data suggest that MHC
      matching might be useful in human islet transplantation.

PMID- 15257058
TI  - HLAMatchmaker algorithm is not a suitable tool to predict the alloreactive
      cytotoxic T-lymphocyte response in vitro.
AB  - Both donor-specific anti-human leukocyte antigen (HLA) antibodies and cytotoxic T
      lymphocytes are important mediators of graft rejection. HLAMatchmaker determines
      the amino acid triplets on antibody-accessible sites of the HLA molecule that are
      not shared between patient and donor. A previous study showed a strong positive
      correlation between the number of triplet mismatches and the percentage of
      individuals producing HLA antibodies. In the present study, we tested whether the
      number of triplet mismatches is predictive for the cytotoxic T-lymphocyte
      precursor (CTLp) frequency in vitro. The analysis was performed on 108 HLA-DRB1
      and DQB1 identical patient-donor combinations registered by the Europdonor
      foundation, with a single HLA class I mismatch and in healthy responder
      stimulator combinations mismatched for at least one HLA class I antigen. The
      results show that there is no strong correlation between the number of triplet
      mismatches and the CTLp frequency. Even in the case of zero triplet mismatches, a
      high CTLp frequency can be found. This lack of correlation is probably caused by
      the fact that HLAMatchmaker considers only triplets on antibody-accessible
      positions, whereas CTLs also recognize other epitopes on the HLA molecule,
      including the bound peptides.

PMID- 15257059
TI  - Retroperitoneoscopic living donor nephrectomy: a retrospective comparison to the
      open approach.
AB  - A purely retroperitoneoscopic approach in living kidney donation is used by only
      a few centers worldwide. Data from 28 consecutive purely retroperitoneoscopic
      living donor nephrectomies (RLDN) were compared to the most recent 30 open living
      donor nephrectomies (OLDN). Right-sided donation was performed in 12 cases (43%)
      of the RLDN and 11 cases (37%) of the OLDN. Comparison of the results between the
      two groups showed a shorter operation time and hospital stay for the RLDN group
      (P < 0.001). Warm ischemia time was significantly shorter in the OLDN group (P <
      0.02). The rate of complications did not differ significantly between the groups.
      No significant difference in terms of renal graft function was detected within 30
      days after surgery. As a result of the direct access, RLDN is superior in terms
      of operation time, even to the open access on our series, while maintaining the
      advantage of minimal invasiveness.

PMID- 15257060
TI  - Portal vein thrombosis complicating islet transplantation in a recipient with the
      Factor V Leiden mutation.

PMID- 15257061
TI  - Pharmacogenetics in immunosuppressive therapy: the best thing since TDM?

PMID- 15257062
TI  - Using established immunosuppressant therapy effectively: lessons from the
      measurement of mycophenolic acid plasma concentrations.
AB  - Getting the most effective use of immunosuppressant medications in transplant
      patients continues to be a major challenge in clinical practice. This need
      applies to established immunosuppressants just as it does to new agents. In this
      review this principle is illustrated for mycophenolic acid, the active metabolite
      of mycophenolate mofetil, the most commonly used immunosuppressant, in various
      combinations with other immunosuppressants, in current clinical practice.
      Defining, as rigorously as possible, the requirements for effective therapeutic
      monitoring of MPA is an important goal given all of the changes in
      immunosuppressive drug regimens. This review will focus on the major factors
      known to influence MPA clearance including: UDP-glucuronyltransferases,
      enterohepatic circulation, MPA free fraction, the effect of time
      posttransplantation, concomitant administration of immunosuppressant drugs. The
      significant variability of MPA pharmacokinetics and the need to deepen our
      understanding of the influence of these factors on MPA clearance are strong
      reasons why additional clinical trials are needed to define best practice
      therapeutic drug monitoring of this drug.

PMID- 15257063
TI  - TDM-based imipramine treatment in neuropathic pain.
AB  - Tricyclic antidepressants (TCA) are the best-documented treatment of neuropathic
      pain. TCAs have a pronounced interindividual pharmacokinetic variability and a
      narrow therapeutic index. The aim of this study was to characterize the plasma
      concentration-effect relationship of imipramine in neuropathic pain and to
      determine the usefulness of therapeutic drug monitoring (TDM) of TCA treatment in
      a population with noncancer chronic pain. To do this, 83 patients with chronic
      noncancer neuropathic pain were included. Information on previous use of TCA was
      collected, and patients were tested for the presence of hyperalgesia. Pain
      intensity and pain relief were recorded, and the Short Form McGill Pain
      Questionnaire and Major Depression Inventory were completed before and during a
      TDM-based imipramine treatment. Imipramine dose was increased in steps of 25 mg/d
      every second week, and blood samples were taken at every dose. Endpoints were
      best possible pain relief, unacceptable side effects, or insufficient pain relief
      despite plasma drug level > 500 nmol/L. Dose range used was 10-300 mg/d. The
      study showed that imipramine 75 mg/d caused a 36-fold interindividual variation
      in steady-state plasma drug concentrations. In 46 responders (global pain relief
      > 25%) the plasma drug concentration at which an individual maximal analgesic
      effect was obtained ranged from 50 to 1400 nmol/L, but for the majority it was
      below 400 nmol/L. The concentration-effect relationship was similar for patients
      with central versus peripheral neuropathic pain and independent of the presence
      of hyperalgesia. Previous treatment failure with non-TDM TCA treatment was not a
      predictor of poor response to TDM-based treatment. In conclusion, there is a
      pronounced interindividual variability in concentration-effect relationship for
      imipramine treatment in neuropathic pain, but the majority of patients obtain a
      maximal analgesic effect at drug levels below 400 nmol/L. The concentration
      effect relationship is similar for patients with central and peripheral
      neuropathic pain. Further studies are needed to document if TDM improves pain
      relief; however, TDM reduces the risk for toxicity.

PMID- 15257064
TI  - Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its
      active metabolite, and its relationship with prolactin response.
AB  - The authors investigated steady-state pharmacokinetics of perospirone and its
      active metabolite hydroxyperospirone (ID-15036) and its prolactin response in 10
      schizophrenic patients receiving 16 mg twice daily. Plasma concentrations of
      perospirone, hydroxyperospirone, and prolactin were monitored just before and up
      to 12 hours after the dosing. Thereafter, the dose was decreased to 8 mg twice
      daily in 8 patients, and drug concentrations were determined. The geometric means
      of peak concentration (Css(max)), time to Css(max) (tmax), area under the plasma
      concentration-time curve from 0 to 12 hours [AUC (0-12)], and elimination half
      life at steady state were 8.8 ng/mL, 0.8 hours, 22.0 ng x h/mL, and 1.9 hours,
      respectively, for perospirone, and those of Css(max), tmax, and AUC (0-12) for
      hydroxyperospirone were 29.4 ng/mL, 1.1 hours, and 133.7 ng x h/mL, respectively.
      There were no differences in dose-normalized Css(max) or AUC (0-12) perospirone
      and hydroxyperospirone between 16 mg/day and 32 mg/day of perospirone. Changes in
      prolactin concentration from 1 to 2 hours after the dosing were parallel with
      drug concentrations, and almost normal ranges of prolactin concentration were
      observed before the morning dose despite steady state. The current study
      indicated that perospirone is rapidly absorbed and rapidly eliminated, which
      influences the prolactin response. The active metabolite hydroxyperospirone may
      play an important role in the antipsychotic effect because the plasma
      concentration of this metabolite is higher than that of the parent compound.

PMID- 15257065
TI  - Chirality in the new generation of antidepressants: stereoselective analysis of
      the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine
      by LC-MS.
AB  - Mirtazapine is an antidepressant that acts specifically on noradrenergic and
      sertonergic receptors. A LC-MS method was developed that allows the simultaneous
      analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR),
      demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR
      treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC
      separation on a Chirobiotic V column, and MS detection in electrospray mode. The
      limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra-
      and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A
      method is also presented for the quantitative analysis of glucuroconjugated MIR
      and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide.
      Preliminary data suggest that in all patients, except in those comedicated with
      CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations
      were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit
      the metabolism of MIR. Therefore, this method seems to be suitable for the
      stereoselective assay of MIR and its metabolites in plasma of patients
      comedicated with MIR and other drugs for routine and research purposes.

PMID- 15257066
TI  - Levetiracetam therapeutic monitoring in patients with epilepsy: effect of
      concomitant antiepileptic drugs.
AB  - The authors assessed the effect of concomitant antiepileptic therapy on steady
      state plasma concentrations of the new anti-epileptic drug (AED) levetiracetam in
      a cohort of 100 adult patients with epilepsy. On the basis of concomitant AEDs,
      patients were divided into two groups, otherwise comparable for age, gender,
      weight-adjusted daily dose of levetiracetam, and dosing frequency: group A (n =
      65), receiving levetiracetam plus AED inducers of cytochrome P450 (CYP)
      metabolism, such as carbamazepine, phenobarbital, and phenytoin; group B (n =
      35), receiving levetiracetam plus AEDs without inducing properties of CYP
      metabolism, namely valproic acid and lamotrigine. Plasma levetiracetam
      concentrations were measured by HPLC with spectrophotometric detection. Median
      morning trough levetiracetam plasma concentrations were significantly lower in
      patients of group A than in patients of group B (10.4 microg/mL versus 14.7
      microg/mL, P < 0.001). Median weight-normalized levetiracetam apparent oral
      clearance (CL/F) was 1.3-fold in patients receiving AED inducers compared with
      patients on AED noninducers (1.93 versus 1.45 mL x min(-1) x kg, P < 0.001). No
      gender-related difference was observed in CL/F values. Levetiracetam plasma
      concentrations were linearly related to daily drug doses, regardless of
      concomitant AED therapy, over a dose range from 500 to 5000 mg/d, although at a
      given daily dose an appreciable interpatient variability was observed in matched
      plasma drug concentrations. Concomitant AED inducers can contribute to
      variability in levetiracetam disposition in patients with epilepsy. The observed
      differences were moderate and possibly of minor clinical significance.

PMID- 15257067
TI  - Distribution of diazepam and nordiazepam between plasma and whole blood and the
      influence of hematocrit.
AB  - The binding of drugs to plasma proteins is important to consider when
      concentrations in whole blood (eg, in forensic toxicology) are compared with
      therapeutic and toxic concentrations based on the analysis of plasma or serum.
      The plasma to whole blood distribution of diazepam (D) and its major metabolite
      nordiazepam (ND) was investigated under in vitro and ex vivo conditions. Studies
      in vitro were done by spiking whole blood with D and ND to give concentrations
      ranging from 0.1 to 1.0 microg/g. Venous blood was also obtained from hospital
      blood donors (n = 66) after informed consent. The hematocrit, hemoglobin, and
      water content of blood specimens were determined by routine procedures before D
      and ND were added to produce target concentrations of approximately 0.5 microg/g
      for each substance. The ex vivo work was done with blood specimens from hospital
      outpatients who were being medicated with D. Concentrations of D and ND were
      determined in body fluids by capillary column gas chromatography after adding
      prazepam as internal standard and solvent extraction with butyl acetate. The
      method limit of quantitation was 0.03 microg/g for both D and ND. The
      concentrations of D and ND were highest in plasma and lowest in erythrocytes. The
      plasma/blood (P/B) distribution ratios did not depend on drug concentration
      between 0.1 and 1.0 microg/g. The mean P/B ratios were 1.79:1 for D and 1.69:1
      for ND when hematocrit was 45%. Furthermore, the P/B ratio for D (y) was
      positively correlated with blood hematocrit (x) and the regression equation was y
      = 0.636 + 0.025x (r = 0.86, P < 0.001). A similar strong association was found
      between the P/B ratio and hematocrit for ND (r = 0.79). P/B ratios of D and ND,
      blood hematocrit, hemoglobin, and the water content differed between sexes (P <
      0.001). The overall mean P/B ratios for D and ND were 1.69 +/- 0.097 (+/- SD) and
      1.62 +/- 0.08 (P < 0.001, n = 66) respectively when the mean hematocrit was 42.9
      +/- 3.4 (+/- SD). For forensic purposes, it would be better to forgo making any
      conversion of a drug concentration measured in whole blood to that expected in
      plasma or serum; instead, therapeutic and toxic concentrations should be
      established for the actual specimens received.

PMID- 15257068
TI  - Plasma risperidone concentrations during combined treatment with sertraline.
AB  - The effect of sertraline on the steady-state plasma concentrations of risperidone
      and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was studied in
      11 patients with schizophrenia or schizoaffective disorder. To treat concomitant
      depressive symptoms, additional sertraline, at the dose of 50 mg/d, was
      administered for 4 weeks to patients stabilized on risperidone (4-6 mg/d). Mean
      plasma concentrations of risperidone, 9-OH-risperidone, and the active moiety
      (sum of the concentrations of risperidone and 9-OH-risperidone) did not change
      significantly during combined treatment with sertraline. At the end of week 4,
      sertraline dosage was adjusted in some patients on the basis of the individual
      response and then maintained until the end of week 8. At final evaluation, mean
      plasma levels of risperidone active moiety were not modified in the 4 patients
      who were still receiving the initial sertraline dose, but concentrations were
      slightly but not significantly increased (by a mean 15% over pretreatment) in the
      subgroup of 5 subjects treated with a final dose of 100 mg/d. In the 2 patients
      receiving the highest dose of sertraline, 150 mg/d, at week 8 total plasma
      risperidone concentrations were increased by 36% and 52%, respectively, as
      compared with baseline values. Sertraline coadministration with risperidone was
      well tolerated, and no patient developed extrapyramidal symptoms. These findings
      indicate that sertraline at dosages up to 100 mg/d is not associated with
      clinically significant changes in plasma risperidone concentrations. However,
      higher doses of sertraline may elevate plasma risperidone levels, presumably as a
      result of a dose-dependent inhibitory effect of sertraline on CYP2D6-mediated 9
      hydroxylation of risperidone.

PMID- 15257069
TI  - Population pharmacokinetics of ethanol in drinking drivers using breath measures.
AB  - This study was undertaken to evaluate the population pharmacokinetic behavior of
      ethanol from breath ethanol measures and to see if these results could be used to
      establish the drinking history of our drinking drivers. The population consisted
      of 55 self-identified light to heavy drinkers. All had been arrested at least
      once for driving under the influence of alcohol. Sixteen were women, and 39 were
      men. Breath was analyzed for ethanol using a 3-wavelength infrared
      spectrophotometer. An iterative 2-stage Bayesian (IT2B) parametric modeling
      program was used first to obtain gamma, a measure of the relative magnitude of
      the intraindividual variability. The nonparametric adaptive grid (NPAG) maximum
      likelihood program, using gamma, was then used to obtain the full nonparametric
      joint parameter density. A 2-compartment Michaelis-Menten model was evaluated.
      The 2-compartment model gave a gamma of 1.75. Thus, the standard deviation (SD)
      of the nonassay sources of intraindividual variability was 1.75 times the SD of
      the assay itself for the 2-compartment model. The NPAG program gave the following
      means, medians, modes, and standard deviations for the 2-compartment model: ka
      (h(-1)) = 6.43, 5.46, 2.93, 4.58; Vmax (g/h) = 12.09, 11.90, 13.03, 3.73; Km
      (g/L) = 0.1273, 0.1367, 0.1991, 0.0528; Vc (L) = 31.32, 29.30, 24.88, 10.52; kcp
      (h(-1)) = 4.38, 1.30, 1.12, 6.16; and kpc (h(-1)) = 9.11, 2.47, 0.89, 8.98. These
      drinking drivers had a rate of metabolism of ethanol that was between that of
      moderate drinkers and confirmed alcoholics. Properly collected breath ethanol
      measures can be useful in a therapeutic drug-monitoring situation to obtain
      quick, accurate, and reliable measures of a patient's ethanol concentrations.

PMID- 15257070
TI  - A population pharmacokinetic-metabolism model for individualizing ciprofloxacin
      therapy in ophthalmology.
AB  - The purpose of this study was to construct a population pharmacokinetic (PK)
      metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and
      vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day
      oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous,
      and aqueous humor samples were collected from patients at different times on the
      day of surgery. Patients were phenotyped for CYP 1A2 activity using caffeine.
      Ciprofloxacin and caffeine concentrations were determined using validated HPLC
      assays. All concentrations of ciprofloxacin were simultaneously modeled using a
      four-compartment PK-MB model. Creatinine clearance and CYP 1A2 activity were
      modeled as surrogate markers of renal and hepatic clearances, respectively.
      Population PK was performed with IT2S, and simulations were performed with ADAPT
      II. No eye infections were observed in any of the patients enrolled in the study,
      and there were only minimal effects on vitreous and aqueous concentrations after
      ocular drops were added to the oral treatments. The model that best described the
      concentrations of ciprofloxacin in serum and in aqueous and vitreous humor was a
      four-compartment PK linear model. Simulated AUCs of ciprofloxacin mean
      concentrations in the aqueous and vitreous humors were 17 +/- 9 and 10 +/- 8% of
      the systemic AUC, respectively. The terminal elimination half-life of the
      compound was (mean +/- SD) 5.0 +/- 2.8 hours. The apparent volume of distribution
      (Vss/F) was calculated to be 122.1 +/- 39.7 L. This PK-MB model may be very
      useful in optimizing treatments of various eye infections with ciprofloxacin. The
      results of this study suggest that giving ciprofloxacin orally for 2 days
      preceding surgery may prevent endophthalmitis from occurring, consequently
      abrogating the need for administering antibiotics via intraocular injections.

PMID- 15257071
TI  - Area-under-the-curve monitoring of prednisolone for dose optimization in a stable
      renal transplant population.
AB  - BACKGROUND: Renal transplant recipients were noted to appear cushingoid while on
      low doses of steroid as part of a triple therapy immunosuppression of cyclosporin
      A (CsA), prednisolone, and azathioprine. METHODS: The study group comprised adult
      renal transplant recipients with stable graft function who had received their
      renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men
      and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control
      group was healthy nontransplant subjects [median dose 10 mg (10-30)].
      Prednisolone bioavailability was measured using a limited 6-hour area under the
      curve (AUC), with prednisolone measured using specific HPLC assay. RESULTS: The
      median prednisolone AUC/mg dose for all transplant recipients was significantly
      greater than the control group by approximately 50% (316 nmol x h/L/mg
      prednisolone versus 218). AUC was significantly higher in female recipients
      (median 415 versus 297 for men) and in recipients receiving cyclosporin (348
      versus 285). The highest AUC was in women on estrogen supplements who were
      receiving cyclosporin (median 595). A significantly higher proportion of patients
      on triple therapy had steroid side effects compared with those on steroid and
      azathioprine (17/27 versus 4/15), more women than men had side effects (14/16
      versus 7/22), and the AUC/mg prednisone was greater in those with side effects
      than without (median 377 versus 288 nmol x h/L/mg). DISCUSSION: The results are
      consistent with the hypothesis that CsA increases the bioavailability of
      prednisolone, most likely through inhibition of P-glycoprotein. The increased
      exposure to steroid increased the side-effect profile of steroids in the majority
      of patients. Because the major contributor to AUC is the maximum postdose
      concentration, it may be possible to use single-point monitoring (2 hours
      postdose) for routine clinical studies.

PMID- 15257072
TI  - Cyclosporin A absorption profiles in pediatric renal transplant recipients
      predict the risk of acute rejection.
AB  - The current focus of cyclosporin A (CsA) monitoring in adult transplantation for
      optimized immunosuppression is on the early portion of the CsA area under the
      concentration-time curve (AUC), particularly in the first 4 hours postdose,
      designated as AUC(0-4), and on the blood concentration 2 hours postdose (C2) as a
      highly predictive marker for AUC(0-4). Because data in pediatric patients are
      scarce, full-time (12 hours) and absorption profiles of CsA were analyzed in
      relation to CsA effectiveness in 61 pediatric renal transplant recipients aged
      3.2 to 17.4 years on an immunosuppressive triple regimen with CsA, mycophenolate
      mofetil, and methylprednisolone. CsA dosing was based on body surface area and
      adjusted to CsA trough levels. Pharmacokinetic (PK) profiles were obtained 1 and
      3 weeks (initial period) and 3 and 6 months posttransplant (stable period).
      Patients with an AUC(0-4) < 4400 microg x h/L at both PK sampling periods in the
      first 3 weeks posttransplant had an adjusted relative risk of 48.4% to suffer an
      acute rejection episode (ARE), whereas in patients with at least 1 AUC0-4 above
      this threshold, the adjusted relative risk for an ARE was only 13.1% (P < 0.02).
      The single PK parameters C0 or C2 did not discriminate between patients with and
      without acute rejection. The PK parameters C1.25 (r2 = 0.64) or C2 (r2 = 0.60)
      showed a stronger relationship to the absorption profile (AUC(0-4)) than C0 (r2 =
      0.15). An abbreviated profile consisting of the PK variables C(0.5;2) or
      C(0;0.5;2) showed the closest correlation to the absorption profile (r2 = 0.89)
      and the lowest percentage prediction error. These data indicate that absorption
      profiling in pediatric renal transplant recipients has the potential to optimize
      immunosuppressive therapy with CsA.

PMID- 15257073
TI  - A new, rapid, fully automated method for determination of fluconazole in serum by
      column-switching liquid chromatography.
AB  - A sensitive and rapid HPLC assay for the determination of fluconazole in serum is
      described. HPLC-integrated sample preparation allows direct injection of serum
      samples without any pretreatment. The in-line extraction technique is carried out
      by automatically switching from the extraction column (Lichrospher ADS C8) to the
      analytic column (Nucleosil C18). After 6 minutes the matrix passes the extraction
      column, and the retained analyte is quantitatively transferred to the analytic
      column, where separation by isocratic HPLC is performed. The extraction eluent is
      sodium dihydrogen phosphate buffer, pH 5.0 (50 mM), and the analytic eluent is
      acetonitrile/sodium dihydrogen phosphate buffer, pH 5.0 (50 mM) (26.8/73.2,
      vol/vol). Fluconazole is detected according to its absorption maximum at 210 nm.
      The lower limit of quantification (LLOQ) is 0.65 microg/mL, the limit of
      detection (LOD) is 0.2 microg/mL, and the quantification range is 0.65-23.3
      microg/mL. The assay was precise with a between-run coefficient of variation of <
      or = 5.59%. The within-run accuracy was 99.8% and 103.4%, and the between-run
      accuracy was 99.2% and 99.7%, respectively, for the concentrations 23.3 microg/mL
      and 1.3 microg/mL. The recovery was 78%. The described procedure allows sample
      cleanup and determination within 20 minutes, thereby facilitating drug monitoring
      in clinical routine. The method was applied successfully.

PMID- 15257074
TI  - Nonfatal instances of intoxication with gamma-hydroxybutyrate in the United
      Kingdom.
AB  - There has been much publicity regarding the use and abuse of gamma
      hydroxybutyrate (GHB, "liquid ecstasy," or "GBH"). GHB has been found to be an
      endogenous compound but has also been used for various therapeutic applications
      in addition to illicit use, particularly as a dietary supplement, sexual adjunct,
      and "party drug." Toxicological analysis was performed using urine and/or plasma
      specimens from 27 nonfatal instances of suspected GHB intoxication in the United
      Kingdom between May 1998 and May 2003. GHB was detected in the plasma and urine,
      invariably with the additional presence of ethanol and other drugs of abuse (eg,
      amphetamines, cocaine, and morphine). GBL was also detected in the majority of
      urine specimens analyzed but was not detected in the plasma samples (<10 mg/L).
      The mean plasma and urine concentrations measured as "total GBL" were found to be
      245 mg/L (range 86-551 mg/L) and 1732 mg/L (range 5-5581 mg/L), respectively.
      This is believed to be the largest compilation of nonfatal cases from the United
      Kingdom.

PMID- 15257075
TI  - Studies on the human metabolism and the toxicologic detection of the cough
      suppressant dropropizine in urine using gas chromatography-mass spectrometry.
AB  - Studies are described on the metabolism and the toxicologic analysis of the
      nonopioid cough suppressant dropropizine [R,S-3-(4-phenyl-1-piperazinyl)1,2
      propandiol, DRO] in human urine using gas chromatography-mass spectrometry (GC
      MS). The metabolism studies showed that DRO was metabolized in humans mainly by
      hydroxylation of the aromatic ring, by N-dealkylation of the parent drug and of
      the hydroxyl-metabolite to the corresponding N-phenylpiperazines, and by
      degradation of the piperazine moiety. The authors' systematic toxicologic
      analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid
      liquid extraction, and microwave-assisted acetylation allowed the unambiguous
      detection of DRO and its above-mentioned metabolites in human urine up to about
      32 hours after intake of a single common therapeutic dose. The target analytes
      were found to be the parent compound DRO (earlier phase of excretion) and the
      hydroxylated metabolite para-hydroxy-DRO (later phase of excretion). Both allowed
      unambiguous detection of an intake of DRO and also differentiation from other
      phenylpiperazine derivatives.

PMID- 15257076
TI  - Beta2-microglobulin adsorption column reduces digoxin trough level during
      hemodialysis: three case reports.
AB  - We have previously reported that a beta2-microglobulin adsorption column for the
      treatment of dialysis-related amyloidosis decreased serum digoxin concentration
      in renal failure patients. Because the distribution volume of digoxin is high, it
      is uncertain whether the repetitive use of this column influences the
      pharmacokinetics of digoxin in renal failure patients. We have observed 3 renal
      failure patients whose trough serum digoxin concentrations were significantly
      reduced by the repetitive use of tandem beta2-microglobulin adsorption columns
      for treatment of dialysis-related amyloidosis. These patients experienced
      symptomatic elevation of their heart rates in parallel with a significant
      reduction in serum digoxin concentrations. Termination of the use of the
      adsorption column improved the symptoms in 1 patient; however, severe arthritic
      pain caused by amyloidosis relapsed. Dosage of digoxin was increased in 2 other
      patients with continuous treatment by the column. Their digoxin concentrations
      increased, and their heart rates decreased without any deterioration of joint
      pain. We have demonstrated that the repetitive use of the beta2-microglobulin
      adsorption column in tandem with standard hemodialysis actually decreases trough
      digoxin concentration in renal failure patients. Careful monitoring and
      alteration of digoxin dosage regimens are needed under these circumstances.

PMID- 15257077
TI  - Severe toxicity associated with a markedly elevated mycophenolic acid free
      fraction in a renal transplant recipient.
AB  - A 58-year-old man with end-stage renal failure secondary to polycystic kidney
      disease developed a profoundly elevated mycophenolic acid (MPA) free fraction and
      associated severe toxicity after cadaveric renal transplantation. Initial
      immunosuppressive therapy was 4 mg/kg body weight bid cyclosporin (Neoral;
      Novartis Pharmaceutical Co Ltd, Sydney, Australia) given orally with 1 g bid
      mycophenolate mofetil (MMF) (CellCept; Roche Products Pty Ltd, Sydney,
      Australia). In the first 5 days posttransplantation, the serum creatinine
      concentration fell, and the patient developed profound hypoalbuminemia (serum
      albumin <20 g/L) and hyperbilirubinemia (serum bilirubin >150 micromol/L) that
      resulted from progressing biliary obstruction. On day 5 posttransplantation, the
      2-hour whole-blood cyclosporin concentration and total MPA area under the curve
      (AUC(0-6)) were low (837 microg/L and 12.6 mg x h/L, respectively), while the
      total mycophenolic acid glucuronide (MPAG) AUC(0-6) was elevated (1317 mg x h/L).
      MMF was continued at the same dose, but tacrolimus substituted for cyclosporin.
      The patient subsequently experienced severe nausea, vomiting, hematemesis, and
      pancytopenia (nadir white cell count 1.6 x 10(9)/L, platelet count 32 x 10(9)/L,
      and hemoglobin 73 g/L) that were normalized after cessation of MMF. Retrospective
      measurement of the free MPA concentration on day 5 showed that free MPA AUC(0-6)
      was markedly elevated at 2.3 mg x h/L, as was the free fraction, at 18.3%. This
      case illustrates how altered protein binding can be associated with severe MMF
      toxicity caused by an increased free MPA concentration despite relatively low
      total MPA. These data support the monitoring of free MPA concentrations in those
      patients considered at risk for MMF-related toxicity.

PMID- 15257078
TI  - Race is not associated with nevirapine pharmacokinetics.
AB  - The effect of race on the pharmacokinetics of nevirapine was investigated in a
      nonselected population. Included patients were ambulatory HIV-1-infected patients
      from the outpatient clinics of the Academic Medical Center and the Slotervaart
      Hospital, Amsterdam, The Netherlands. All patients were using nevirapine as part
      of their antiretroviral regimen and had at least one plasma concentration
      available for analysis. From the included patients, gender, age, race, hepatitis
      C status, baseline ASAT value, and body weight were obtained. The nonlinear mixed
      effect modeling program (NONMEM) version V 1.1 was used for all analyses.
      Population pharmacokinetic parameters [clearance (CL/F), volume of distribution
      (V/F), absorption rate constant (ka)] and interindividual (IIV) and interoccasion
      variability (IOV) were estimated. The influence of race on the CL/F of nevirapine
      was tested as Negroid race versus the other races, Asian race versus the other
      races, and the Negroid and the Asian races as separate variables versus the
      Caucasian race. A database of 1732 nevirapine plasma concentrations of 383 HIV-1
      infected individuals collected during 1186 outpatient clinic visits was available
      for this analysis. The conclusion of this study is that race is not associated
      with the pharmacokinetics of nevirapine, and thus requires no dose adaptations.

PMID- 15257079
TI  - Assessment of storage and transport stability of new antidepressant and
      antipsychotic drugs for a nationwide TDM service.

PMID- 15257080
TI  - Cardiac troponin I levels are a risk factor for mortality and multiple organ
      failure in noncardiac critically ill patients and have an additive effect to the
      APACHE II score in outcome prediction.
AB  - Cardiac troponin I (cTnI) is a specific marker of myocardial damage used in the
      diagnosis of acute coronary syndrome (ACS). Recent studies have shown that cTnI
      levels can also be elevated in patients without ACS, such as in sepsis and trauma
      patients, and that this is associated with an adverse prognosis. We have
      evaluated the clinical implications and prognostic significance of serum cTnI
      levels in noncardiac critically ill patients in a prospective observational study
      in a general medical intensive care unit at a tertiary-level hospital. A total of
      108 consecutive patients without ACS or other cardiac disease was enrolled. Serum
      cTnI levels were measured on admission using enzyme-linked immunoabsorbant assay
      kits. Clinical laboratory parameters and outcome were compared between patients
      with elevated and normal cTnI levels. The prognostic significance of cTnI levels
      and the Acute Physiology And Chronic Health Evaluation (APACHE) II score was also
      analyzed. Forty-nine patients (45%) had elevated cTnI levels and 59 (55%) had
      normal levels. Compared with patients with normal cTnI levels, patients with
      elevated levels had a higher incidence of new failure of two or more organs, had
      a lower left ventricular ejection fraction during admission, were more likely to
      be associated with bacteremia, and had a higher intensive care unit mortality;
      they also had a significantly shorter survival over a 180-day follow up, before
      and after stratification by the APACHE II score. Multiple organ failure was the
      leading cause of mortality in patients with elevated cTnI levels. By multivariate
      analysis, elevated cTnI levels, a high APACHE II score, and underlying cancer
      were the three most important independent predictors for a shorter survival.
      Combination analysis showed a shorter survival in patients with a high APACHE II
      score plus elevated cTnI levels than in patients with a high APACHE II score or
      elevated cTnI levels alone. In conclusion, elevated serum cTnI levels is a risk
      factor for multiple organ failure and mortality in noncardiac critically ill
      patients, and the cTnI levels and APACHE II score have an additive effect in
      outcome prediction.

PMID- 15257082
TI  - Polymorphonuclear neutrophils in posttraumatic osteomyelitis: cells recovered
      from the inflamed site lack chemotactic activity but generate superoxides.
AB  - The pathogenesis of posttraumatic osteomyelitis, one of the major complications
      after orthopedic surgery, is not yet understood. Formation of bacterial biofilms
      on the implant is presumed, conferring resistance to antibiotic therapy and
      probably also to the host defense mechanisms. In that context, the
      polymorphonuclear neutrophils (PMN) having infiltrated the infected site were
      recovered and characterized phenotypically and functionally. Loss of CD62L and
      upregulation of CD14 were seen, as was expression of CD83. Expression of the
      latter is dependent on de novo protein synthesis and thus is indicative of an
      extended life span and a transdifferentiation of the PMN at the infected site.
      The infiltrated PMN had lost their chemotactic activity, whereas the capacity to
      produce superoxides was preserved and in some patients even enhanced. In vitro
      experiments done in parallel showed that long-term culture with interferon-gamma
      resulted in similar alterations of PMN: loss of chemotactic activity, whereas
      other functions of PMN, such generation of superoxides and phagocytosis of
      opsonized bacteria, were preserved or even enhanced. The loss of the migratory
      capacity of PMN having already emigrated from the blood vessel to the infected
      site is not expected to affect the host defense negatively. Assuming, however,
      that bacteria are organized as a biofilm and that infiltration into this biofilm
      is required for phagocytosis of the bacteria, our data could to some extent
      explain why despite being activated, the PMN are not able to control the
      infection. By releasing their cytotoxic, proteolytic, and collagenolytic
      potential, PMN might instead contribute to tissue destruction and eventually to
      osteolysis.

PMID- 15257081
TI  - Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic
      brain injury.
AB  - S100B protein (S100B) has been described as a marker of brain injury. Various
      cytokines also increase in the cerebrospinal fluid (CSF) of patients with severe
      traumatic brain injury (TBI). Thus, we investigated early changes in the
      concentrations of CSF S100B and various cytokines after TBI and evaluated the
      relations of both S100B and cytokines to intracranial pressure (ICP) and
      prognosis. Twenty-three patients with severe TBI and a Glasgow Coma Scale score
      of 8 or less on admission were included in this study. CSF and serum samples were
      obtained on admission and at 6, 12, 24, 48, 72, and 96 h after injury. CSF
      concentrations of S100B and CSF and serum concentrations of five cytokines (IL
      1beta, TNF-alpha, IL-6, IL-8, and IL-10) were measured and compared. The CSF
      S100B concentration was increased for 6 h after injury and decreased thereafter.
      The CSF concentrations of IL-6 and IL-8 peaked within 6 h after injury; other
      cytokines (IL-1beta, TNF-alpha, and IL-10) were elevated for 24 h after injury
      and gradually decreased thereafter. Peak CSF S100B concentrations correlated
      significantly with ICP determined at the time CSF samples were taken (r = 0.729,
      P < 0.0001). For the cytokines investigated, only the peak CSF IL-1beta
      concentration correlated significantly and positively with the peak CSF S100B
      concentration (r = 0.397, P < 0.005). Peak CSF concentrations of S100B (1649 +/-
      415 microg/L, mean +/- SEM) and IL-1beta (16.5 +/- 3.3 pg/mL) in the 6 patients
      with high ICP were significantly higher than those (233 +/- 67 microg/L, 7.6 +/-
      1.7 pg/mL, respectively) in the 17 patients with low ICP (P < 0.05). The CSF
      S100B concentration (1231 +/- 378 microg/L) in eight patients with an unfavorable
      outcome was significantly higher than that (267 +/- 108 microg/L) in 15 patients
      with a favorable outcome (P < 0.05). The CSF IL-1beta concentration (14.8 +/- 3.4
      pg/mL) in eight patients with an unfavorable outcome tended to be higher than
      that (7.3 +/- 1.5 pg/mL) in 15 patients with a favorable outcome (P = 0.057). CSF
      concentrations of S100B and cytokines peak within 24 h after severe TBI and
      decrease gradually thereafter. CSF S100B and IL-1beta may be useful as predictors
      of outcome in cases of severe TBI.

PMID- 15257083
TI  - Cortisol levels and adrenal reserve after successful cardiac arrest
      resuscitation.
AB  - The postresuscitation phase after out-of-hospital circulatory arrest shares
      similarities with severe sepsis. Corticosteroid replacement is beneficial in
      patients with septic shock and adrenal dysfunction. The goal of this study was to
      assess baseline cortisol and adrenal reserve of out-of-hospital circulatory
      arrest patients after recovery of spontaneous circulation. Thirty-three
      consecutive patients successfully resuscitated after cardiac arrest were
      prospectively included between March 2002 and June 2003. A serum cortisol assay
      and a corticotropin test (250 microg i.v.) were done 6 to 36 h after circulatory
      arrest. A cortisol increase smaller than 9 microg/dL after corticotropin
      (nonresponders) defined adrenal reserve insufficiency. Response status was
      compared in the three outcome groups: survival with full neurologic recovery (n =
      4), early death from refractory shock (n = 10), or later death from neurologic
      dysfunction (n = 19). Patients who died of early refractory shock had lower
      baseline cortisol levels than patients who died of neurologic dysfunction (27
      microg/dL [15-47] vs. 52 microg/dL [28-73], respectively; P < 0.01), suggesting
      an inadequate adrenal response to severe systemic inflammation. Corticotropin
      response status was not associated with standard severity markers and seemed
      uninfluenced by therapeutic hypothermia. In conclusion, patients who die of early
      refractory shock after cardiopulmonary resuscitation may have an inadequate
      adrenal response to the stress associated with this condition. Thresholds for
      cortisol levels at baseline and after corticotropin need to be determined in this
      clinical setting.

PMID- 15257084
TI  - Remote trauma sensitizes hepatic microcirculation to endothelin via caveolin
      inhibition of eNOS activity.
AB  - This study addresses the microvascular mechanisms by which a remote, mild stress
      such as blunt trauma sensitizes the liver to injury. Rats received closed femur
      fracture (FFx), and 24 h later livers were isolated and perfused at a similar
      starting flow rate for assessment of vascular response to endothelin-1 (ET-1).
      Sinusoidal volumetric flow (QS), red blood cell velocity (VRBC), and sinusoidal
      diameter (Ds) were determined by intravital microscopy. Baseline portal
      resistance in livers from FFx rats was not changed. The FFx group showed a lower
      baseline VRBC (322.9 +/- 26.4 and 207.3 +/- 17.2 microm/s in sham and FFx,) and
      QS (28.4 +/- 4.2 and 17.6 +/- 2.1 pL/s in sham and FFx, P < 0.05). ET-1 caused a
      decrease in the VRBC in sham but no change after FFx. In contrast, Ds was
      unchanged by ET-1 in sham but decreased in FFx (10.3 +/- 0.4 to 10.7 +/- 0.5 vs.
      10.6 +/- 0.4 to 9.0 +/- 0.4 microm at 10 min in sham and FFx groups, P < 0.05).
      The overall result of these changes was a greater decrease in sinusoidal flow in
      FFx compared with sham. There was no significant change in mRNA for ET-1,
      endothelin A (ETA) receptor, or iNOS (inducible nitric oxide synthase) in FFx
      compared with sham. However, endothelin B (ETB) receptor mRNA and eNOS
      (endothelial nitric oxide synthase) mRNA were increased in the FFx group (ETB,
      54.81 +/- 8.08 in sham vs. 83.28 +/- 8.19 in FFx; eNOS, 56.11 +/- 2.53 in sham
      vs. 83.31 +/- 5.51 in FFx; P < 0.05) while the levels of these proteins remained
      unchanged. Caveolin-1 (cav-1) protein levels were elevated in FFx, and
      coimmunoprecipitation with both ETB and eNOS showed increased associations with
      these proteins, suggesting a possible inactivation of eNOS. The eNOS activity was
      also blunted in FFx animals in the presence of increased cav-1 expression. Taken
      together, these results demonstrate that remote trauma sensitizes the liver to
      the sinusoidal constrictor effect of ET-1. We propose that this
      hyperresponsiveness occurs as a result of uncoupling of the ETB receptor from
      eNOS activity mediated by interaction of eNOS and possibly the ETB receptor with
      increased caveolin-1. This vascular sensitization that occurs after FFx may
      contribute to the exacerbation of injury during subsequent stresses.

PMID- 15257085
TI  - Beneficial effect of an inhibitor of leukocyte elastase (EPI-hNE-4) in presence
      of repeated lung injuries.
AB  - Persistence of alveolar neutrophil influx and activation may enhance the fibrotic
      process after acute lung injury. On the other hand, elastase has an antimicrobial
      activity and could participate in neutrophil migration, both events being
      critically important in host defense, explaining the controversial issue of
      therapeutic elastase inhibition in the setting of acute lung injury. We assessed
      the effect of a neutrophil elastase inhibitor, EPI-hNE-4, in single (bleomycin,
      1.2 mg/rat intratracheally) and repeated (bleomycin, 1.2 mg/rat plus endotoxin
      and 1 mg/kg intratracheally 24 h later) lung injuries to assess the role of
      neutrophil in fibrosis. Subsequently, the effect of EPI-hNE-4 on bacterial
      clearance was evaluated during Pseudomonas aeruginosa-induced pneumonia. In the
      single injury model, despite a dramatic reduction of alveolar neutrophil influx
      with EPI-hNE-4 treatment, no significant inhibition of the decrease in
      respiratory system compliance, an index of lung fibrosis, was demonstrated at day
      14. In the repeated injury model, EPI-hNE-4 treatment afforded a significant
      protective effect on compliance and alveolar inflammation at day 14. During
      bacterial pneumonia, EPI-hNE4 did not modify alveolar neutrophil recruitment or
      bacterial clearance from bronchoalveolar lavage fluid and lung homogenate. In
      conclusion, EPI-hNE-4, a specific inhibitor of leukocyte elastase, afforded a
      partial protective effect on the respiratory system compliance during repeated
      lung injuries, and had no detrimental effect during a gram-negative bacterial
      pneumonia.

PMID- 15257087
TI  - Use of low tidal volume in septic shock may decrease severity of subsequent acute
      lung injury.
AB  - Recent studies have indicated that protective lung strategies may improve
      outcomes in acute lung injury. We hypothesized that the use of a lower tidal
      volume early during septic shock may protect against the subsequent development
      of acute lung injury. Fourteen fasted, anesthetized, invasively monitored,
      mechanically ventilated, female sheep (26.4 +/- 4.5 kg) underwent cecal ligation
      and perforation to induce sepsis. Sheep were then randomized to ventilation with
      low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory
      pressure of 10 cm H(2)O was applied in each case. Ringer's lactate was titrated
      to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive
      agents or antibiotics were used. Survival time was longer in the low- than in the
      high-tidal-volume group (21.8 +/- 2.4 vs. 17.6 +/- 4.1 h, respectively, P <
      0.05). The times to develop hypotension and anuria were longer in the low-tidal
      volume group (18.1 +/- 3.1 vs. 12.0 +/- 2.8 h, P < 0.05, and 17.6 +/- 1.6 vs.
      14.1 +/- 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low-
      than in the high-tidal-volume group (P = 0.06), postmortem examination showed a
      lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group
      (7.1 +/- 0.5 vs. 9.1 +/- 0.7, P < 0.05). A low-tidal-volume ventilation strategy
      applied early during septic shock may be beneficial in terms of reducing the
      amount of lung edema and prolonging survival time.

PMID- 15257086
TI  - Polymicrobial sepsis induces divergent effects on splenic and peritoneal
      dendritic cell function in mice.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that act as
      sentinels in the cell-mediated response against invading pathogens associated
      with septic challenge. The purpose of the present study was to determine whether
      there is a loss of dendritic cells and/or changes in function of these cells in
      septic mice. Here we report that the number of DCs, in both spleen and
      peritoneum, decreased over 24 h postsepsis [cecal ligation and puncture (CLP)]
      when compared with sham. The most dramatic change was seen in the peritoneal
      cavity. This decrease appeared to be caused mainly by the depletion of immature
      DCs rather than mature DCs. This change was LPS independent and minimally
      affected by FasL; however, overexpression of human Bcl-2 gene provides protection
      of the septic peritoneal DCs. Moreover, although the level of IL-12 release
      decreased significantly in splenic DCs obtained from CLP mice, IL-12 secretion
      was markedly elevated by peritoneal DCs as well as in both plasma and peritoneal
      fluid at 24 h post-CLP. In peritoneal cells, the expression of CD40, CD80, and
      CD86 was unchanged, but their respective ligands CD40L, CD28, and CD152 all
      increased in mice 24 h after CLP, although no such change was observed in
      splenocytes. Regardless of the presence or absence of antigen, peritoneal DCs
      from CLP mice showed higher capacity to stimulate T-cell proliferation than those
      cells from the sham control. However, splenic DCs from CLP mice only showed
      augmented capacity to induce antigen-dependent stimulation of T-cell
      proliferation. Together, these data indicate that sepsis produces divergent
      functional changes in splenic and peritoneal DC populations.

PMID- 15257088
TI  - Survival in a rat model of lethal hemorrhagic shock is prolonged following
      resuscitation with a small volume of a solution containing a drag-reducing
      polymer derived from aloe vera.
AB  - Drag-reducing polymers (DRP) increase tissue perfusion at constant driving
      pressure. We sought to evaluate the effects of small-volume resuscitation with a
      solution containing a DRP in a rat model of hemorrhage. Anesthetized rats were
      hemorrhaged at a constant rate over 25 min. In protocol A, total blood loss was
      2.45 mL/100 g, whereas in protocol B, total blood loss was 3.15 mL/100 g. Five
      minutes after hemorrhage, the animals were resuscitated with 7 mL/kg of either
      normal saline (NS) or NS containing 50 microg/mL of an aloe vera-derived DRP. In
      protocol B, a third group (CON) was not resuscitated. Whole-body O2 consumption
      (Vo2) and CO2 production (Vco2) were measured using indirect calorimetry. In
      protocol A, 5/10 rats in the NS group and 8/10 rats in the DRP group survived for
      4 h (P = 0.14). Mean arterial pressure was higher in the DRP-treated group than
      in the NS-treated group 45 min after resuscitation (89 +/- 8 vs. 68 +/- 5 mmHg,
      respectively; P < 0.05). In protocol B, survival rates over 2 h in the DRP, NS,
      and CON groups were 5/15, 1/14, and 0/7, respectively (P < 0.05). Compared with
      NS-treated rats, those resuscitated with DRP achieved a higher peak Vo2 (9.0 +/-
      1.0 vs. 6,3+/- 1.0 mL/kg/min) and Vco2 (9.0 +/- 1.1 vs. 6.0 +/- 1.0 mL/kg/min)
      after resuscitation. We conclude that resuscitation with a small volume of DRP
      prolongs survival in rats with lethal hemorrhagic shock.

PMID- 15257089
TI  - Glucagon regulates hepatic inducible nitric oxide synthesis in vivo.
AB  - The inducible nitric oxide synthase (iNOS) is stimulated to produce large
      quantities of nitric oxide (NO) by proinflammatory stimuli, hemorrhagic shock,
      and a variety of cytokines. We have previously shown that cAMP profoundly
      inhibits hepatocyte iNOS expression in vitro. In this study, we tested whether
      glucagon, a hormone that increases cAMP in hepatocytes, could regulate hepatic
      iNOS expression and activity in vivo. Rats were injected intraperitoneally with
      lipopolysaccharide (LPS, 10 mg/kg) and treated with either saline or glucagon
      (500 microg/kg i.p.). Plasma and liver tissue were obtained 6 and 24 h after LPS.
      LPS induced increased iNOS mRNA, iNOS protein, and plasma levels of
      nitrite/nitrate that were all significantly decreased by glucagon treatment. The
      reduction in iNOS expression produced by glucagon was associated with a reduction
      in plasma AST and LDH levels, suggesting decreased LPS-induced hepatic injury.
      These data suggest that glucagon may participate in the in vivo regulation of
      hepatic iNOS expression after proinflammatory stimuli.

PMID- 15257090
TI  - Recombinant factor VIIa increases the pressure at which rebleeding occurs in
      porcine uncontrolled aortic hemorrhage model.
AB  - In trauma patients, resuscitation to endpoints below normal blood pressure (BP)
      levels may reduce further blood loss due to the rebleeding often caused by more
      aggressive resuscitation. However, patients whose BP is maintained at lower
      levels for extended periods are at increased risk for organ failure. The purpose
      of this study was to determine whether recombinant activated factor VII (rFVIIa)
      raises the BP level at which rebleeding occurs in a prospective, randomized,
      blinded study using a porcine model of uncontrolled hemorrhage and resuscitation.
      Thirty anesthetized 40-kg pigs were assigned to three groups (n = 10/group):
      control, low-dose rFVIIa (180 microg/kg), or high-dose (720 microg/kg). Vehicle
      or drug was infused 5 min before creating a 2.0-mm infrarenal aortotomy. Ten
      minutes later, resuscitation with lactated Ringer's (LR) solution at 100 mL/min
      was begun. Hemorrhage and LR volumes and BP were recorded continuously. We found
      that pretreatment with rFVIIa increased the mean arterial pressure at which
      rebleeding occurred during resuscitation (45 +/- 3, 69 +/- 5, and 66 +/- 6 mmHg
      in the control, low-dose, and high-dose groups, respectively, P = 0.003). Rebleed
      hemorrhage volume was reduced with rFVIIa (39 +/- 9, 22 +/- 7, and 26 +/- 5 mL/kg
      for control, and low and high dose, respectively; P = 0.055). This is the first
      study to show that rFVIIa increases the BP at which rebleeding occurs during
      resuscitation in an injury to a major artery, suggesting the formation of a
      tight, stronger fibrin plug in the presence of high concentrations of rFVIIa.

PMID- 15257091
TI  - Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic
      skin wounds.
AB  - Wound healing in ischemic tissues such as flap margins due to inadequate blood
      supply is still a source of considerable morbidity in surgical practice. Adequate
      tissue perfusion is particularly important in wound healing. We investigated the
      effects of recombinant human erythropoietin (rHuEPO) on wound healing in an
      ischemic skin wound model. Sixty-three Sprague-Dawley rats were used. Normal
      incisional wound and H-shaped double flaps were used as the wound models. Animals
      were treated with rHuEPO (400 IU/kg) or its vehicle. Rats were killed on
      different days (3, 5, and 10 days after skin injury) and the wounded skin tissues
      were used for immunohistochemistry and for analysis of vascular endothelial
      growth factor content and collagen content. Tissue transglutaminase
      immunostaining of histological specimens was used as a vascular marker to
      determine the level of microvessel density. The results showed a higher level of
      vascular endothelial growth factor protein and an increased microvessel density
      in ischemic wounds with rHuEPO treatment than the normal incisional wounds and
      ischemic control wounds. Collagen content was higher in the incisional wounds and
      in the ischemic wounds with rHuEPO treatment compared with the ischemic control
      wounds. Our results suggest that erythropoietin may be an effective therapeutic
      approach in improving healing in ischemic skin wounds.

PMID- 15257092
TI  - Protection against an Escherichia coli-induced sepsis by alkaline phosphatase in
      mice.
AB  - Alkaline phosphatase (AP) is a phosphate transferase present in bacteria and
      eukaryotes. In previous studies, we have shown that AP is able to dephosphorylate
      lipopolysaccharide (LPS) at physiological pH levels. Because LPS is the causative
      agent of gram-negative sepsis, we hypothesize that AP might be used as a
      medication during early stages of LPS-induced septic shock. We have demonstrated
      protective effects of AP when this enzyme was administered simultaneously with
      LPS. However, a major question of anti-LPS therapies is whether they are also
      effective after systemic infiltration of whole bacteria and if they also act in
      later stages of the disease. To test this, we explored the protective effects of
      AP from human placenta (plAP) in a bacterial challenge model in Balb/c mice. AP
      was intravenously administered 20 min after a bacterial intraperitoneal
      inoculation of 2 to 5 x 10 CFU of Escherichia coli suspended in a 100-microL
      volume of saline. It was shown that AP attenuated the systemic host response upon
      E. coli. Body temperature was normalized as compared with untreated septic mice.
      Also, serum nitric oxide levels 24 h after the injection of bacteria were reduced
      almost to control levels in mice that received AP. Moreover, survival after 24 h
      was significantly higher in the AP-treated group compared with the nontreated
      control group.

PMID- 15257093
TI  - N(omega)-nitro-L-arginine methyl ester effects on neutrophil function and
      bacterial clearance.
AB  - Nitric oxide synthase (NOS) inhibitors are considered promising as a therapeutic
      option in severe septic shock. The aim of this study was to investigate the
      effects of N-nitro-L-arginine methyl ester (L-NAME) application on neutrophil
      (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from
      blood and tissue in rabbits. Twenty-eight female chinchilla rabbits were
      randomized to a treatment and control group. To quantify the bacterial clearance
      process, 10 colony forming units (CFU) of E. coli were injected intravenously
      into anesthetized rabbits. Animals in the L-NAME group had a significantly higher
      mortality compared with controls. NOS inhibition resulted in a significant delay
      of bacterial clearance (P < 0.001). These findings correlated with a significant
      augmentation of all organ E. coli findings (P = 0.002-0.035). PMN phagocytosis
      activity was notably reduced by L-NAME treatment during the experimental
      observation. Neutrophil burst, on the other hand, was amplified by NOS inhibition
      (P = 0.008). Our findings point to an interference with the PMN-dependent immune
      mechanisms after L-NAME treatment. The augmented PMN burst reaction could be a
      compensatory mechanism, potentially leading to tissue damage. Therefore, in this
      model, we find sufficient evidence pointing to a possible cause for the
      deleterious effect of early nonselective NOS inhibition in critically ill
      patients.

PMID- 15257094
TI  - Endotoxin increases plasma soluble tumor necrosis factor-related apoptosis
      inducing ligand level mediated by the p38 mitogen-activated protein kinase
      signaling pathway.
AB  - Despite extensive knowledge about the mechanisms behind sepsis, this syndrome
      still caries a large morbidity and mortality rate. Dysregulated immune and
      coagulation systems are held responsible. However, additional pathophysiological
      mechanisms such as uncontrolled apoptosis induced by death receptor ligands might
      well play a role. P38 mitogen-activated protein (MAP) kinase inhibitors are
      considered as potential drugs in inflammatory diseases. Therefore, the effect of
      endotoxin administration on the response of soluble(s) tumor necrosis factor
      related apoptosis-inducing ligand (sTRAIL), a death receptor ligand, and the role
      of p38 MAP kinase inhibition was studied in 21 human volunteers. The volunteers
      received 30 min before the endotoxin infusion a single oral dose of placebo or
      the selective p38 MAP kinase inhibitor drug, RWJ-67657. Plasma sTRAIL increased
      10-fold to 6564 +/- 511 pg/mL after 2.5 h. This increase was blocked completely
      by the highest dose of RW-J6765. This is the first report showing that endotoxin
      increases sTRAIL where the p38 MAP kinase signaling pathway is involved.

PMID- 15257095
TI  - Re: Humane endpoints in shock research.

PMID- 15257097
TI  - Can we distinguish between different types of local perfusion/metabolic
      derangement by regional venous concentrations of intermediary energy substrates?

PMID- 15257098
TI  - The extracellular matrix differentially regulates the expression of PTHrP and the
      PTH/PTHrP receptor in FG pancreatic cancer cells.
AB  - OBJECTIVES: Previous studies by our laboratory have demonstrated that parathyroid
      hormone-related protein (PTHrP) and its receptor (PTH/PTHrP receptor) are
      commonly expressed in pancreatic cancer and suggest their participation in the
      progression of this devastating disease. It has also been demonstrated that one
      of the major hallmarks of pancreatic adenocarcinoma is an increased production of
      the extracellular matrix (ECM), a critical regulator of diverse cellular
      processes such as differentiation, proliferation, and angiogenesis. The present
      study focused on the relationship between the PTHrP and ECM axes in the
      pathobiology of pancreatic cancer. METHOD AND RESULTS: Using the FG pancreatic
      adenocarcinoma cell line, we demonstrate a significant inverse correlation
      between FG cell proliferation and PTHrP expression that depended on the ECM
      protein on which the cells were cultured (P < 0.05). Generally, ECM proteins that
      promoted the strongest proliferation, including type I collagen, type IV
      collagen, and laminin, resulted in decreased expression of PTHrP. Conversely, ECM
      proteins that promoted the weakest proliferation, including fibronectin,
      vitronectin, and BSA, resulted in increased expression of PTHrP. A similar trend
      was found between FG cell proliferation and the PTH/PTHrP receptor expression,
      with Pearson correlation coefficients of 0.480 (mRNA) and -0.591 (protein).
      CONCLUSION: These observations demonstrate a unique functional relationship
      between the ECM and PTHrP axes and have important implications for our
      understanding of the complex mechanisms responsible for the progression of
      pancreatic cancer and its metastases.

PMID- 15257099
TI  - Genistein-induced changes in gene expression in Panc 1 cells at physiological
      concentrations of genistein.
AB  - OBJECTIVES: To investigate the effect of genistein on gene expression in Panc 1
      cells using microarray technology. METHODS: Panc 1 cells were treated with 10
      micromol/L genistein or DMSO (vehicle control) for 0, 1, 3, 6, or 12 hours. Total
      RNA from each sample was isolated, and biotin-labeled probes were hybridized to
      the human genome U133A chip, after which the chip was washed and scanned. Data
      were analyzed using DMT software (Affymetrix). For genes that showed large
      changes in expression due to genistein, these changes were confirmed using real
      time PCR assays. RESULTS: Two independent microarray experiments showed that
      genistein significantly changed the expression of 47 genes: up-regulating of egr
      1 and IL-8 and down-regulating of EGF-R AKT2, CYP1B1, NELL2, SCD, DNA ligase III,
      Rad as well as 18s and 28s rRNA and others. These alterations in expression were
      confirmed using real-time PCR, although the increase in change was not exactly
      the same in the 2 assays. CONCLUSIONS: Our data suggest the reported apparent
      ability of genistein to inhibit carcinogenesis may involve a number of pathways.
      The most obvious target is the EGF-R signaling pathway since the expression of 5
      genes related to this pathway was reduced (EGFR, egr-1, AKT2, CYP1B1, and NELL2).
      Genistein may also act by disabling cancer cell self-protection by inhibiting
      expression of AKT2, CYP1B1, and DNA ligase III. Furthermore, genistein may
      inhibit car-cinogenesis by inhibiting expression of SCD. Finally, our data
      support findings indicating that genistein inhibits rRNA formation, which is an
      important mechanism by which genistein regulates tumor cell growth.

PMID- 15257101
TI  - Caspase-3 inhibitor prevents apoptosis of human islets immediately after
      isolation and improves islet graft function.
AB  - OBJECTIVES: Apoptosis appears in islets after isolation, and it has a detrimental
      effect on the islet function. To improve the outcome of clinical islet
      transplantation, it is crucial to protect islets from apoptosis. The aim of this
      study was to determine whether a caspase-3 inhibitor (Z-DEVD-FMK) added to
      culture media protects islets from apoptosis and to compare the effects of fetal
      bovine serum (FBS) with human serum albumin (HSA) as a protein supplement in
      culture. METHODS: Isolated human islets were cultured under 4 different
      conditions: 0.5% HSA (control), 0.5% HSA + 25 micromol/L Z-DEVD-FMK, 0.5% HSA +
      100 micromol/L Z-DEVD-FMK and 10% FBS for 2 days. Next, 1000 IEQ islets
      precultured with 0.5% HSA and with or without 100 micromol/L Z-DEVD-FMK were
      transplanted to diabetic nude mice. RESULTS: The islet yields were higher in Z
      DEVD-FMK-treated groups, and the inhibitor prevented apoptosis dose dependently.
      The yield and insulin release were higher in FBS-treated group than in the
      control group, but FBS did not affect apoptosis. All 6 mice transplanted with
      islets pretreated with Z-DEVD-FMK, and 3 of 8 mice with control islets became
      normoglycemic posttransplantation. CONCLUSION: Z-DEVD-FMK prevented apoptosis of
      isolated human islets and improved its function. FBS (10%) improved the islet
      yield and insulin secretion more than 0.5% HSA.

PMID- 15257100
TI  - Expression of the beacon gene in the rat pancreatic islets: opposite effects of
      beacon (47-73) protein (ubiquitin-like protein 5) on insulin secretion in vivo
      and insulin release by isolated islets.
AB  - OBJECTIVE: Beacon gene expression is elevated in the hypothalamus of the Israeli
      sand rat (Psammomys obesus), an animal that is used as a polygenic animal model
      of obesity and NIDDM. We performed studies aimed at investigating the expression
      of beacon mRNA and protein in pancreatic islets of the rat and the possible
      beacon protein effects on insulin secretion. METHODS: Rat pancreatic islets were
      isolated by the collagenase digestion technique. Beacon mRNA expression was
      demonstrated in isolated islets using RT-PCR and beacon-like immunoreactivity
      using immunocytochemistry (ICC) on a sections of Bouin-fixed pancreas. Isolated
      islets were incubated with 1-100 nmol/L beacon (47-73) protein in normoglycemic
      medium. Adult female rats were subcutaneously injected with beacon (47-73) at
      doses 0.35 or 0.7 nmol/100 g body weight and killed after 30 and 60 minutes.
      RESULTS: RT-PCR results indicate the presence of beacon mRNA in isolated rat
      pancreatic islets. Beacon-like immunoreactivity is present in all cell types of
      the Langerhans islet. Beacon inhibits insulin secretion from isolated islets. In
      contrast, a bolus administration of beacon at a lower dose notably stimulates
      blood insulin concentration at 30 and 60 minutes of the experiment while the
      higher dose does not change insulinemia. None of the treatment had an effect on
      blood glucose concentration. CONCLUSION: This study demonstrated the presence of
      beacon mRNA in isolated rat islets as well as a direct inhibitory effect of
      beacon protein on insulin secretion by isolated rat pancreatic islets. The data
      obtained suggest that beacon may be involved in physiologic regulation of insulin
      secretion.

PMID- 15257102
TI  - Novel insulin-releasing peptides in the skin of Phyllomedusa trinitatis frog
      include 28 amino acid peptide from dermaseptin BIV precursor.
AB  - OBJECTIVE: The granular glands of amphibians have long been known to produce many
      biologically active compounds. The aim of this study was to isolate and
      characterize insulinotropic peptides from the skin of Phyllomedusa trinitatis
      frog. METHODS AND RESULTS: Crude secretions obtained by mild electrical
      stimulation of the dorsal skin surface were purified by reverse phase HPLC
      yielding 80 fractions. In acute incubations with glucose-responsive BRIN-BD11
      cells, fractions 39-40 (band 1) and fractions 43-46 (band 2) significantly
      stimulated insulin release by 1.5 to 2.5-fold. Pooled fractions in bands 1 and 2
      were rechromatographed to 4 homogeneous peaks, each with insulin-releasing
      activity. Mass spectrometry analysis was successfully completed for 3 peptides,
      indicating 2996.4, 3379.9, and 8326.4 Da. The sequence of the 2996.4 Da peptide
      was determined as ALWKDILKNVGKAAGKAVLNTVTDMVNQ. This 28-amino-acid peptide has
      100% homology with the C-terminal of the 75-amino-acid dermaseptin BIV precursor
      of a family of structurally related antimicrobial peptides in the skin of the
      Phyllomedusinae subfamily. CONCLUSION: These data demonstrate that the defensive
      skin secretions of P. trinitatis contain biologically active peptides, which may
      have mammalian counterparts and merit further investigation as insulin
      secretagogues.

PMID- 15257103
TI  - Histologic and immunohistochemical comparison of intraductal tubular carcinoma,
      intraductal papillary-mucinous carcinoma, and ductal adenocarcinoma of the
      pancreas.
AB  - OBJECTIVE: To analyze the differences between intraductal tubular carcinoma (ITC)
      and intraductal papillary-mucinous carcinoma (IPMC), we performed light
      microscopic and immunohistochemical analysis of 4 cases of ITC, 6 cases of IPMC,
      and 9 cases of ductal adenocarcinoma of the pancreas. METHODS AND RESULTS: Light
      microscopic examination showed no hyperplasia or adenoma around the carcinoma in
      ITC, and immunohistochemical analysis showed that the apical side of the cell
      membrane was positive for MUC-1 in almost all ITC cells. In contrast to ITC
      cells, all IPMC cells were negative for MUC-1 and ductal adenocarcinoma cells
      were strongly positive for MUC-1 in the cytoplasm and cell membrane.
      Immunohistochemical staining patterns of DUPAN-2 in ITC resembled those of MUC-1
      in these cancers. ITC and IPMC cells were negative for carcinoembryonic antigen,
      but ductal adenocarcinoma cells were positive. There were no apparent differences
      in proliferative activity between ITC and IPMC, but ductal adenocarcinoma showed
      significantly greater activity than either ITC or IPMC. CONCLUSION: The PCNA-L.I
      of IPMC and ITC was lower and the cell atypia of them was more mild compared with
      those of ductal carcinoma, indicating that IPMC possess low-grade malignant
      potentials. However, we observed differences of growth patterns and mucous
      secretion between ITC and IPMC of the pancreas.

PMID- 15257104
TI  - Inhibition and mechanism of action of a protease inhibitor in human pancreatic
      cancer cells.
AB  - OBJECTIVES: Tumor-associated trypsinogen (TAT), urokinase-type plasminogen
      activator (u-PA), matrix metalloproteinase-2 (MMP-2), and MMP-9 each play a
      dominant role in the degradation of extracellular matrix (ECM) during the
      invasion process of pancreatic cancer. Transforming growth factor beta1 (TGF
      beta1) is a multifunctional poly-peptide that regulates cell growth and
      differentiation, ECM deposition, cellular adhesion properties, angiogenesis, and
      also immune functions. We previously reported that TGF-beta1 up-regulated
      vascular endothelial growth factor (VEGF) production and protease production of
      MMP-2 and of u-PA in the highly metastatic pancreatic cancer cell lines SW1990
      and CAPAN-2. In this study, we examined the inhibitor effects of a protease
      inhibitor, gabexate mesilate (GM), on cell invasion, cell proliferation, growth
      factor production, and ECM degradation. We also examined the effect of GM on the
      production of growth factor and ECM degradation by these cell proteases and
      enzymatic activities. RESULTS: GM down-regulated the invasiveness and liver
      metastasis potential of SW1990 and CAPAN-2 cells, but it did not affect the
      proliferation of these cells. GM inhibited not only the enzymatic activities of
      TAT and u-PA but also the production of MMP-2, and u-PA, all of which have been
      known to be secondarily down-regulated by TGF-beta1. CONCLUSIONS: These findings
      suggested that GM has very good potential for use in the treatment against
      invasion and metastasis of pancreatic cancer.

PMID- 15257105
TI  - The influence of platelets on the promotion of invasion by tumor cells and
      inhibition by antiplatelet agents.
AB  - OBJECTIVE: Using a chemoinvasion assay, we show that platelets promote
      invasiveness of 5 pancreatic adenocarcinoma cell lines. METHODS: Gelatin
      zymography and Western blot analysis were performed to detect metalloproteinase-9
      (MMP-9) secreted from tumor cells in the presence or absence of platelets. The
      effects of antiplatelet agents on the invasiveness of tumor cells and the
      secretion level of MMP-9 were evaluated. RESULTS: The number of traversed tumor
      cells significantly increased when incubated with platelets compared without
      platelets in all cell lines. The MMP-9 band was detected in all tumor cell lines,
      and the intensity was obviously greater in conditions of incubation with
      platelets than without. In the experiment of antiplatelet agents effects, it was
      confirmed that invasiveness of tumor cells significantly decreased following
      incubation with cilostazol depending on the concentration in spite of the
      presence of platelets. The level of MMP-9 also significantly decreased in the
      ELISA analysis. CONCLUSIONS: These data mean platelets activate invasiveness of
      tumor cells because of enhanced MMP-9 secretion. Furthermore, anti-platelet drugs
      may inhibit invasiveness of tumor cells due to decreased MMP-9 secretion, and
      this inhibition may lead to the suppression of tumor cell invasion. We propose
      that antiplatelet agents are applicable in clinical treatment to inhibit
      metastasis of malignant tumor cells.

PMID- 15257106
TI  - Mechanisms of inhibition of growth of human pancreatic carcinoma implanted in
      nude mice by somatostatin receptor subtype 2.
AB  - OBJECTIVES: Several studies reported that somatostatin receptor subtypes,
      especially subtype 2 (SSTR2), exerted their cytostatic and/or cytotoxic effects
      on various types of tumors. The aim of this study was to investigate the
      antitumor effect of SSTR2 gene transfer to the pancreatic cancer cell line PC-3
      and the mechanisms involved in this effect. METHODS: The full-length human SSTR2
      cDNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine
      mediated transfection; positive clones were screened by G418, and stable
      expression of SSTR2 was detected by the immunohistochemical SABC method and RT
      PCR. Athymic mice were separately xenografted with SSTR2-expressing cells
      (experimental group), vector control, and mock control cells. TUNEL assay was
      used to determine the apoptotic index (AI) in the tumors of these groups. The
      immunohistochemical SP method was used to determine expression of apoptosis
      regulating genes Bcl-2 and Bax and re-expression of SSTR2 and to assess
      intratumoral microvessel density (MVD). Moreover, tumor volume and weight were
      compared among these 3 groups. RESULTS: Restoration of SSTR2 was observed in the
      experimental group both in vitro and in vivo. The AI was significantly higher in
      the experimental group (3.39 +/- 0.84%) compared with that in the vector control
      (0.69 +/- 0.08%) and mock control (0.68 +/- 0.09%) (P < 0.05). MVD was
      significantly lower in the experimental group (6.30 +/- 1.71) than that in the
      vector control (12.64 +/- 1.69) and mock control (13.50 +/- 1.86) (P < 0.05).
      Furthermore, a significant decrease in Bcl-2 and increase in Bax protein
      expression were detected in the experimental group compared with the vector
      control and mock control (P < 0.05). A significant negative correlation of
      protein expression between Bcl-2/Bax ratio and SSTR2 was observed in these tumors
      (P < 0.05). Tumor volume and weight were significantly decreased in the
      experimental group compared with the vector control and mock control (P < 0.05)
      groups. However, no significant differences were observed between the vector
      control and mock control (P > 0.05). CONCLUSION: Re-expression of the SSTR2 gene,
      the expression of which is frequently lost in human pancreatic adenocarcinoma,
      induces apoptosis, which may be mediated via down-regulation of Bcl-2 and up
      regulation of Bax (alteration of Bcl-2/Bax ratio) and inhibits tumor angiogenesis
      in pancreatic carcinoma, resulting in inhibition of tumor growth.

PMID- 15257107
TI  - Disorders of hemostasis during the surgical management of severe necrotizing
      pancreatitis.
AB  - OBJECTIVES: Several clinical studies of severe necrotizing pancreatitis (SNP)
      suggest profound activation of coagulation as well as activation of the
      fibrinolytic system. The aim of this study was to evaluate the hemostatic
      derangements in patients who were managed for SNP. METHODS: Forty-one operated-on
      patients with SNP were analyzed regarding clinical outcome and activation of the
      coagulation systems. Serial measurement of coagulation, anticoagulation, and
      fibrinolysis parameters: prothrombin time (PT), activated partial thromboplastin
      time (APTT), fibrinogen, antithrombin III (AT III), protein C, plasminogen
      activator inhibitor-1 (PAI-1), d-dimer, alpha2-antiplasmin, and plasminogen were
      performed on days 1, 3, 5, 7, 10, and 14 after the initial operation. According
      to treatment outcome at the end of study, groups of 26 survivors and 15
      nonsurvivors were compared. RESULTS: Nonsurvivors had significantly lower levels
      of activity of protein C and AT III, and higher concentrations of d-dimer and PAI
      1 than survivors. The other measured parameters did not show significant
      differences between the compared groups of patients. CONCLUSIONS: Changes in
      protein C, AT III, d-dimer and PAI-1 levels indicate exhaustion of fibrinolysis
      and coagulation inhibitors in patients with poor outcome during the course of
      SNP.

PMID- 15257108
TI  - Importance of cytokines, nitric oxide, and apoptosis in the pathological process
      of necrotizing pancreatitis in rats.
AB  - OBJECTIVES: Ischemia-reperfusion injury can be involved in the pathophysiology of
      acute necrotizing pancreatitis. The aim of our study was to determine the
      production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6),
      the activation of the inducible nitric oxide synthase (iNOS), and the development
      of apoptosis during this pathologic process. METHODS: Acute pancreatitis was
      produced in male Wistar rats by injection of 200 microL of 6% taurocholic acid
      into the main pancreatic duct in combination with the temporary (15 minutes)
      occlusion of the inferior splenic artery. Six and 24 hours later, the histologic
      damage was evaluated, and serum amylase, TNF, IL-6 levels, and iNOS and apoptotic
      activity from pancreatic and pulmonary tissues were determined. RESULTS: Twenty
      four hours after the induction of pancreatitis, the mortality rate was 63%.
      During this period, the serum TNF and IL-6 levels were permanently high (50 +/-
      12 and 58 +/- 10 U/mL and 7083 +/- 1610 and 6790 +/- 850 U/mL after 6 and 24
      hours, respectively). The iNOS activity showed an increasing tendency in the
      pancreas, and a decrease following an initial increase in the lung (from 4.2 +/-
      0.6 to 5 +/- 0.4 and from 6.8 +/- 0.6 to 3.8 +/- 0.5 pmol/min/mg protein after 6
      and 24 hours, respectively). Histologic examination confirmed severe necrotizing
      pancreatitis. In the pancreas, the apoptotic activity increased significantly
      (from 4 +/- 4 to 27 +/- 5/mm at 6 and 24 hours), while in the lungs, following an
      initial increase it declined during the course of necrotizing pancreatitis (from
      49 +/- 4 to 11 +/- 6/mm at 6 and 24 hours). CONCLUSION: Our results indicate that
      intraductal taurocholic acid and ischemia-reperfusion provokes severe acute
      necrotizing pancreatitis with a high mortality rate and leads to systemic
      inflammatory reaction, which appears to be the consequence of the activation of
      the cytokine cascade and iNOS. The degree of NO overproduction by iNOS
      corresponds with the apoptotic process in the pancreas and the lung.

PMID- 15257109
TI  - Autoimmune pancreatitis associated with immune-mediated inflammation of the
      papilla of Vater: report on two cases.
AB  - Autoimmune pancreatitis (AIP) is defined histologically by periductal and
      interacinar lymphocytic infiltration. Immunohistochemically, the majority of
      these lymphocytes are identified as T cells. Epithelial HLA-DR antigen expression
      was also described as a marker of autoimmunity in this type of chronic
      pancreatitis. We report 2 cases, a 56-year-old man and a 29-year-old woman, with
      AIP associated with immune-mediated inflammation of the main duodenal papilla
      (MDP). Serologically, antinuclear antibody positivity was detected in the male
      patient. The female patient, treated medically for ulcerative proctitis, had no
      serological evidence of autoimmune disease. Macroscopic papillitis was present
      only in the male patient, and endoscopic biopsy samples were taken from this
      swollen MDP. Since we could not exclude malignancy, a pancreatic head resection
      was performed in both patients. The histologic and immunohistochemical studies of
      the resected specimens showed periductal T-lymphocytic infiltration in the
      pancreatic and papillary tissues. Furthermore, HLA-DR-antigen expression was also
      demonstrated in epithelial cells of the pancreas and MDP. The immunohistological
      features of endoscopic biopsy samples from the swollen MDP were identical as in
      the surgically resected specimens. Immune-mediated inflammation of the MDP may be
      associated with AIP.

PMID- 15257110
TI  - Preventing pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis:
      cost effectiveness of IgG4.

PMID- 15257111
TI  - IgG4-positive plasma cells specifically infiltrate various organs in autoimmune
      pancreatitis.

PMID- 15257112
TI  - A mathematical model of the pancreatic duct cell generating high bicarbonate
      concentrations in pancreatic juice.
AB  - OBJECTIVE: To develop a simple, physiologically based mathematical model of
      pancreatic duct cell secretion using experimentally derived parameters that
      generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR
      activation. METHODS: A new mathematical model was developed simulating a duct
      cell within a proximal pancreatic duct and included a sodium-2-bicarbonate
      cotransporter (NBC) and sodium-potassium pump (NaK pump) on a chloride
      impermeable basolateral membrane, CFTR on the luminal membrane with 0.2 to 1
      bicarbonate to chloride permeability ratio. Chloride-bicarbonate antiporters
      (Cl/HCO3 AP) were added or subtracted from the basolateral (APb) and luminal
      (APl) membranes. The model was integrated over time using XPPAUT. RESULTS: This
      model predicts robust, NaK pump-dependent bicarbonate secretion with opening of
      the CFTR, generates and maintains pancreatic fluid secretion with bicarbonate
      concentrations >140 mM, and returns to basal levels with CFTR closure. Limiting
      CFTR permeability to bicarbonate, as seen in some CFTR mutations, markedly
      inhibited pancreatic bicarbonate and fluid secretion. CONCLUSIONS: A simple CFTR
      dependent duct cell model can explain active, high-volume, high-concentration
      bicarbonate secretion in pancreatic juice that reproduces the experimental
      findings. This model may also provide insight into why CFTR mutations that
      predominantly affect bicarbonate permeability predispose to pancreatic
      dysfunction in humans.

PMID- 15257113
TI  - Gastric electrical stimulation is associated with improvement in pancreatic
      exocrine function in humans.
AB  - OBJECTIVE: To define the possible effects of gastric electrical stimulation (GES)
      for gastroparesis on pancreatic function, we performed 2 related human studies.
      METHODS: Fecal elastase values were compared in 2 patient groups: (1) GES devices
      ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to
      prokinetic medications, (2) positive response (RES) to medications, and (3)
      normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and
      OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were
      compared by paired t tests and/or ANOVA and reported as mean +/- SE. RESULTS:
      Elastase was different for GES-ON and OFF (508.0 +/- 92.2 vs. GES-OFF 378.6 +/-
      87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal
      controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P
      = 0.07). HRV revealed a lower percentage of change with device ON versus OFF
      (44.2 +/- 5.5 vs. 48.5 +/- 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9
      +/- 4.5 vs. 25.7 +/- 5.3, P < 0.05). CONCLUSIONS: GES improves exocrine
      pancreatic release, effects autonomic control, and improves GI symptoms,
      suggesting a possible role for GES in the treatment of pancreatic insufficiency
      associated with gastroparesis.

PMID- 15257114
TI  - Natural beta-carotene for the prevention of post-ERCP pancreatitis.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly
      used procedure. Pancreatitis is its most common complication. As the injury may
      be mediated by oxidative stress, it could be ameliorated by antioxidants.
      METHODS: We conducted a double-blind trial, giving the patients a single dose of
      natural beta-carotene or placebo, 12 hours prior to procedure, and monitoring
      them for 24 hours post-procedure for procedure complications, antioxidant levels,
      and plasma oxidation. RESULTS: The overall incidence of acute pancreatitis
      according to our definition was 9.6%. The incidence of pancreatitis was not
      significantly different between the beta-carotene group (10%) and the placebo
      group (9.4%). Four patients in the placebo group had severe pancreatitis (2.22%),
      but none in the beta-carotene group. This difference is statistically
      significant. CONCLUSION: We did not see a reduction in the incidence of post-ERCP
      pancreatitis, but there may be some protective effect of treatment with beta
      carotene regarding the severity of disease.

PMID- 15257116
TI  - New look, same "gold-standard" clinical content.

PMID- 15257115
TI  - Relationships between the autonomic nervous system and the pancreas including
      regulation of regeneration and apoptosis: recent developments.
AB  - Substantial new information has accumulated on the mechanisms of secretion, the
      development, and regulation of the gene expression, and the role of growth
      factors in the differentiation, growth, and regeneration of the pancreas. Many
      genes that are required for pancreas formation are active after birth and
      participate in endocrine and exocrine cell functions. Although the factors that
      normally regulate the proliferation of the pancreas largely remain elusive,
      several factors to influence the growth have been identified. It was also
      reported that the pancreas was sensitive to a number of apoptotic stimuli. The
      autonomic nervous system influences many of the functions of the body, including
      the pancreas. In fact, the parasympathetic nervous system and the sympathetic
      nervous system have opposing effects on insulin secretion from islet beta cells;
      feeding-induced parasympathetic neural activity to the pancreas stimulates
      insulin secretion, whereas stress-induced sympathetic neural activity to the
      pancreas inhibits insulin secretion. Moreover, it has been reported that the
      autonomic nervous system is one of the important factors that regulate pancreatic
      regeneration and stimulate the carcinogenesis. The present review focuses on the
      relationships between the autonomic nervous system and the pancreas, and
      furthermore, presents evidence of the autonomic nervous system-related pancreatic
      regeneration and carcinogenesis.

PMID- 15257118
TI  - Treating community-acquired pneumonia.

PMID- 15257119
TI  - Predicting CAD events: C-reactive protein a marker for atherosclerotic risk.

PMID- 15257121
TI  - Benign prostatic hyperplasia: is it a precursor to prostatic cancer?

PMID- 15257123
TI  - Eradicate H. pylori with effective treatment regimens.

PMID- 15257124
TI  - Diagnosis and management of bedbugs: an emerging U.S. Infestation.
AB  - Bedbug infestations are on the rise in the United States among people of all
      socioeconomic groups. Bedbug bites typically cause pruritic wheals with central
      punctum on exposed skin, which are noted upon awakening. The diagnosis is
      confirmed by identifying fecal smears and blood spots on the bed linens and
      mattress or by identifying the culprit bug. Extermination of bedbugs using
      cleaning techniques and pesticides is necessary to prevent recurrence.

PMID- 15257125
TI  - Making primary care culturally competent.

PMID- 15257126
TI  - Caduet treats two cardiovascular conditions at once.

PMID- 15257127
TI  - Guide to care for patients. Acne.

PMID- 15257129
TI  - Olfactory learning in the rat pup: a model that may permit visualization of a
      mammalian memory trace.
AB  - Over the past 10 years considerable insight into intracellular interactions
      leading to long-term memory formation have been gleaned from various neural
      circuits within invertebrate and vertebrate species. This review suggests that,
      while certain intracellular signaling pathways are commonly involved across
      species, it is important to analyze specific neural systems because critical
      differences among systems appear to exist. The olfactory bulb has been used by
      our group to estimate the influence of neuromodulatory systems (serotonin and
      norepinephrine) on intracellular processes leading to learning. We describe here
      how activation of noradrenergic input to mitral cells increases cAMP leading to
      CREB phosphorylation when paired with a conditioning stimulus, odor. CREB
      phosphorylation is causal in odor preference learning leading to long-term memory
      for the odor. However, the relationship between cAMP activation and CREB
      phosphorylation is not straight forward; overstimulation of cAMP pathways impedes
      learning and prevents CREB phosphorylation. Excessive CREB phosphorylation also
      interferes with learning.

PMID- 15257130
TI  - Auditory neural pathway evaluation on sensorineural hearing loss using diffusion
      tensor imaging.
AB  - Diffusion tensor imaging is a new in vivo tool not only for the assessment of
      white matter structural integrity but also for diagnosis and assessment of
      disease conditions which disturb tissue structural coherence. In this study, we
      investigated the integrity of auditory pathway in patients of sensorineural
      hearing loss by means of fractional anisotropy of water diffusion to see any
      subtle changes of auditory pathways resulting from sensorineural hearing loss. In
      addition, this study suggests that the diffusion anisotropy measured by diffusion
      tensor imaging is highly sensitive to otherwise subtle disease processes not
      normally seen with conventional magnetic resonance imaging or computed tomography
      contrast.

PMID- 15257131
TI  - Identification of some lectin IB4 binding proteins in rat dorsal root ganglia.
AB  - Lectins are proteins that bind to glycoproteins and glycolipids. The isolectin
      Griffonia simplicifolia I-B4 (IB4) recognizes terminal alpha-galactose and binds
      to a subset of small and medium-sized neurons in the dorsal root ganglia (DRG).
      Using one and two-dimensional gel electrophoresis, we have identified several
      proteins that bind IB4 in sciatic nerve, dorsal horn, and DRG. Treatment with the
      enzyme alpha-galactosidase reduces IB4 binding, strongly suggesting the binding
      is specific for the IB4 epitope. Mass spectrometric analysis of tryptic digests
      of alpha-galactosidase sensitive bands identified three proteins that bind IB4:
      the laminin beta 2 chain and the light and medium subunits of neurofilaments.

PMID- 15257132
TI  - Basal forebrain atrophy is a distinctive pattern in dementia with Lewy bodies.
AB  - We determined brain atrophy patterns in dementia with Lewy bodies and Alzheimer's
      disease using voxel-based morphometry, an indirect volumetry. Ten patients with
      dementia with Lewy bodies, 10 patients with Alzheimer's disease and 10 controls
      were included. All groups were matched for age; sex and global differences in
      voxel intensities were included as confounding covariates. We observed basal
      forebrain atrophy discriminating dementia with Lewy bodies from Alzheimer's
      disease. Compared to controls, atrophy of lateral prefrontal cortex and left
      premotor cortex was seen in dementia with Lewy bodies whereas atrophy of the
      medial temporal cortex, posterior parietal cortex, thalamus and temporo-occipital
      areas was observed in Alzheimer's disease. Atrophy of insular cortex was found in
      both patient groups.

PMID- 15257133
TI  - The expression of PARP, NF-kappa B and parvalbumin is increased in Parkinson
      disease.
AB  - Immunohistochemical techniques revealed a significant increase of poly(ADP
      ribose) polymerase (PARP)-containing nuclei in the dopaminergic neurons of the
      substantia nigra (SN) in Parkinson disease and in diffuse Lewy body disease as
      compared with a group of patients with other neurodegenerative diseases and
      normal controls. The nuclear translocation of nuclear factor kappa B (NF-kappa B)
      was also noted in the same cells. The over-activation of PARP and the
      transcriptional activation of NF-kappa B can contribute to the pathomechanism of
      the disease specific lesion of the neurons in the SN. However, in another
      subgroup of dopaminergic cells of the SN an increased parvalbumin content was
      detected reflecting a natural protective mechanism against the putative increase
      of intracellular calcium caused by excitotoxic injury and oxidative stress.

PMID- 15257134
TI  - Primary cultures from fetal bovine brain.
AB  - This study describes a method of obtaining primary cultures from the cerebral
      cortex and the hypothalamus of bovine fetuses. We describe here the influence of
      tissue origin, developmental stage and culture medium conditions on cell
      differentiation and prevalence of neurons vs glial cells. To identify optimal
      conditions for obtaining and growing viable neurons and astrocytes in culture, we
      tested early, middle and late stages of development. Explants from cortex, early
      stages (week 10 of pregnancy out of 36) and low fetal calf serum concentration
      (1%) yielded maximum amounts of neurons. Fresh and thawed tissues gave comparable
      results.

PMID- 15257135
TI  - Imaging melody and rhythm processing in young children.
AB  - In the adult brain, melody and rhythm processing have been found to show
      different hemispheric dominance, with the right hemisphere apparently more
      sensitive to melody and the left hemisphere to rhythm. We used a novel, child
      friendly scanning protocol to examine the neural basis of melody and rhythm
      processing in young children (mean age 6 years 4 months, n=33). FMRI data were
      acquired using a sparse temporal sampling technique, taking advantage of the
      natural delay in the cerebrovascular response to neuronal activity. We found that
      this group of young children showed some differential specialization for melody
      and rhythm processing, but to a lesser extent than previously reported in adults.
      These results suggest that hemispheric specialization for musical processing may
      develop with age.

PMID- 15257136
TI  - Catecholaminergic inputs to aromatase cells in the canary auditory forebrain.
AB  - The caudomedial nidopallium in songbirds is a specialized forebrain auditory
      region involved in the processing of species-typical vocalizations. It receives a
      prominent catecholaminergic projection with many fibers forming basket-like
      structures around non-immunoreactive cells. We investigated in male canaries the
      anatomical relationship between tyrosine hydroxylase and cells immunoreactive for
      the steroid metabolizing enzyme, aromatase, in the caudomedial nidopallium using
      double-label immunocytochemistry. Fibers immunoreactive for tyrosine hydroxylase
      established numerous close contacts with aromatase-immunoreactive cells and often
      encircled these cells to form basket-like structures. Aromatase containing cells
      in the caudomedial nidopallium are therefore a major target of catecholaminergic
      inputs in canary. Interactions between catecholaminergic systems and aromatase in
      the caudomedial nidopallium may provide one mechanism for the regulation of
      estrogens involved in song perception and memorization.

PMID- 15257137
TI  - Rapid neural differentiation of human cord blood-derived mesenchymal stem cells.
AB  - Human umbilical cord blood (UCB) contains hematopoietic stem cells (HSCs) and
      mesenchymal stem cells (MSCs), both of which are regarded as valuable sources for
      cell transplantation and cell therapy. Adherent cells expressing MSCs-related
      antigens such as SH2, CD13, CD29, and ASMA, have been isolated from a mononuclear
      cell fraction of human UCB. Under proneurogenic conditions, these UCB-derived
      adherent cells rapidly assumed the morphology of multipolar neurons. Both
      immunofluorescence and RT-PCR analyses indicated that the expression of a number
      of neural markers including Tuj1, TrkA, GFAP and CNPases, was markedly elevated
      during this acute differentiation. The neurogenic potential of UCB-derived may
      facilitate stem cell therapeutic approaches to neurodegenerative diseases.

PMID- 15257138
TI  - Clusterin shortens the incubation and alters the histopathology of bovine
      spongiform encephalopathy in mice.
AB  - Clusterin accumulates in significant quantity in prion protein lesions associated
      with bovine spongiform encephalopathy (BSE) and we therefore sought to elucidate
      its ability to alter BSE pathogenesis and incubation time by comparison of wild
      type C57BL/6J mice and clusterin knock out (ko) mice. The ko mice had a 40 day
      increase in mean incubation time compared to wild type mice. PrP deposition in
      the medulla was less aggregated in clusterin knock out mice when compared to wild
      type BSE infected mice and a more marked astrocytosis, as determined by GFAP
      staining, was evident. The vacuolation profiles did not differ between the two
      strains of mice. Taken together these results suggest that clusterin alters the
      extracellular deposition of PrP(BSE) and accelerates BSE pathogenesis.

PMID- 15257139
TI  - Elevation of NMDAR after transplantation of neural stem cells.
AB  - Cognitive deficits could be alleviated by transplantation of neural stem cells in
      animals. Grafted cells may differentiate into neurons, thereby improving animal
      cognition. Alternatively, grafted cells may provide neurotrophic factors to
      modify neuronal functions and to alleviate cognitive deficits. To test which
      mechanism is underlying this recovery process, senescence-accelerated mice were
      transplanted with human neural stem cells into the hippocampus. The effect of
      cell transplantation was assessed in the Morris water maze. The survival and
      differentiation of grafted cells and the expression of NMDA receptors were
      examined. The data suggested that in addition to the neural differentiation of
      grafted neural stem cells, up-regulation of NMDA receptors after transplantation
      also contributed to the alleviation of cognitive deficits in this animal model.

PMID- 15257140
TI  - Melittin selectively activates capsaicin-sensitive primary afferent fibers.
AB  - Whole bee venom (WBV)-induced pain model has been reported to be very useful for
      the study of pain. However, the major constituent responsible for the production
      of pain by WBV is not apparent. Intraplantar injection of WBV and melittin
      dramatically reduced mechanical threshold, and increased flinchings and paw
      thickness. In behavioral experiments, capsaicin pretreatment almost completely
      prevented WBV- and melittin-induced reduction of mechanical threshold and
      flinchings. Intraplantar injection of melittin increased discharge rate of dorsal
      horn neurons only with C fiber input from peripheral receptive field, which was
      completely blocked by topical application of capsaicin to sciatic nerve. These
      results suggest that both melittin and WBV induce nociceptive responses by
      selective activation of capsaicin-sensitive afferent fibers.

PMID- 15257141
TI  - Environmental enrichment improves cognition in aged Alzheimer's transgenic mice
      despite stable beta-amyloid deposition.
AB  - Environmental enrichment (EE) has been shown to improve cognitive performance and
      brain indices of cognition in normal mice and rats. Because the therapeutic
      potential of intensive, long-term EE to benefit patients with Alzheimer's disease
      (AD) has yet to be explored, the present study evaluated the effect of long-term
      EE on cognition in an animal model of AD, the APPsw transgenic mouse. Beginning
      at 16 months of age, APPsw mice were put into EE or standard housing for 4 months
      and then tested in four cognitive-based tasks (Morris maze, circular platform,
      platform recognition, and radial arm water maze) between 20 and 22 months of age.
      Our results indicate that long-term EE of aged APPsw mice results in global,
      overall improvement in cognitive function across these tasks without decreasing
      brain beta-amyloid (A beta) deposition. The results suggest that long-term
      EE/cognitive stimulation could provide cognitive stabilization or improvement to
      AD patients through mechanisms independent of A beta deposition and clearance.

PMID- 15257142
TI  - Manserin, a novel peptide from secretogranin II in the neuroendocrine system.
AB  - We have isolated a novel 40 amino acid neuropeptide, designated manserin, from
      the rat. Manserin is derived from secretogranin II (SgII), a member of granin
      acidic secretory protein family by proteolytic processing, as previously reported
      secretoneurin and EM66. Immunohistochemical analysis using anti-manserin antibody
      revealed that manserin localized in the endocrine cells of the pituitary anterior
      lobe, but not in the posterior lobe. Interestingly, manserin never co-localized
      with ACTH in the anterior pituitary, which is in contrast with SgII, suggesting
      specific immunoreactivity of the antiserum against manserin. Manserin
      immunostaining was also observed in the neuronal cells of several hypothalamic
      nuclei and the neurons in the median eminence. These results suggest that
      manserin exerts a specific role in the neuroendocrine system.

PMID- 15257143
TI  - Characterization of genetically labeled catecholamine neurons in the mouse
      retina.
AB  - Mouse neurons were labeled transgenically with red fluorescent protein (RFP)
      driven by the tyrosine hydroxylase (TH) promoter and observed in living retinas
      and brain slices. Two types of retinal amacrine cells expressed TH::RFP. One type
      had large cell bodies, processes that ramified in S1 of the inner plaxiform layer
      (IPL) and were TH immunoreactive, identifying them as dopaminergic neurons. A
      second type had smaller somas, ramified in S3 and lacked TH. Dopaminergic cells
      had large dendritic fields and exceptionally long axon-like processes, whereas
      type 2 cells were more compact. Neither cell type exhibited tracer coupling.
      Thus, murine retinal dopaminergic neurons exhibit functional anatomy similar to
      their primate counterparts and TH::RFP mice are useful for in situ
      characterization of catecholaminergic neurons.

PMID- 15257144
TI  - Human auditory event-related processes in the time-frequency plane.
AB  - Sensory stimuli produce phase-locked and non-phase-locked changes in brain
      activity as indexed by EEG and MEG. Time-frequency methods such as wavelets, when
      carefully applied, allow simultaneous analysis of both types of activity. Here we
      used wavelets of different time and frequency resolutions in combination with
      spatial mapping to identify these processes. We found that auditory stimulation
      leads to a pattern of large-magnitude power increases and small-magnitude power
      decreases. The power increases, ranging from the theta to the beta frequency
      band, were accounted for by the transient auditory responses P50m, N100m and
      P200m. Following these responses, we observed a power reduction of non-phase
      locked activity which occurred 250-500 ms after stimulus onset in the 14-24 Hz
      frequency range and could be localized to the temporal and parietal brain areas.
      These results indicate that auditory event-related processes consist not only of
      the well-established transient responses but also of power reductions of ongoing,
      non-phase-locked brain processes.

PMID- 15257146
TI  - Tuberoinfundibular peptide of 39 residues decreases pain-related affective
      behavior.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) is a recently identified
      parathyroid hormone 2 receptor ligand. Their CNS distributions suggest potential
      involvement in neuroendocrine, limbic and sensory processing functions. Herein we
      investigate the analgesic and antinociceptive actions of brain delivery of TIP39
      in adult male rats. Intracerebroventricular (i.c.v.) TIP39 did not change hot
      plate paw withdrawal latency or formalin test behavioral responses. TIP39
      partially reversed tactile withdrawal hypersensitivity following carageenan
      administration. In the place/escape avoidance paradigm (PEAP), which evaluates
      affective components of responses to noxious stimuli by presenting a choice
      between a naturally preferred environment paired with stimulation of a
      carrageenan sensitized paw and a less preferred environment paired with
      stimulation of a less sensitive paw, TIP39 decreased the apparent aversiveness of
      sensitive paw stimulation. Because acute sensory thresholds were unaffected by
      TIP39, and the effects of i.c.v. TIP39 were opposite in direction from previously
      described effects of intrathecal TIP39, this suggests that TIP39 may modulate an
      affective component of nociception within the brain.

PMID- 15257145
TI  - Potentiation of sural nerve Abeta action potential after neurogenic inflammation.
AB  - Inflammatory mediators modulate voltage-gated sodium channels through protein
      kinase-mediated pathways. However, it is not clear whether neurogenic
      inflammation may also alter the properties of distantly located channels along
      axon shafts supplying the inflamed dermatome. In this study, localized
      inflammation was induced via intradermal injection of capsaicin within the
      receptive field of the sural nerve, and compound action potentials (CAP) evoked
      by sural nerve stimulation were recorded from the sciatic nerve proximally. The
      area measured under the A beta CAP increased significantly within 5 min after
      capsaicin injection. Distal injection of lidocaine at the ankle division of the
      sural nerve prior to capsaicin injection reversed this increase. In addition,
      application of a lipophilic protein kinase inhibitor H7 (100 microM) through a
      perfusion chamber placed on the sciatic nerve also reversed this increase. Our
      results suggest that during neurogenic inflammation, action potential activity is
      increased, triggering activation of protein kinases that may rapidly alter
      membrane conductance to potentiate action potential propagation along peripheral
      nerves.

PMID- 15257147
TI  - Inflammation of rat dorsal root ganglia below a mid-thoracic spinal transection.
AB  - Macrophages and T-lymphocytes invade the spinal cord in and around a lesion and
      spinal microglia are converted into macrophages. After spinal transection at T8
      in rats, T-lymphocyte and major histocompatibility complex II+ (MHC II+)
      macrophage numbers were increased within dorsal root ganglia (DRGs) below the
      lesion. Inflammation was greater in DRGs closer to the site of transection. After
      8 weeks, MHC II+cell density had fallen by 30% but T-lymphocyte numbers were
      undiminished. In lumbosacral DRGs, inflammation preceded inflammation within the
      spinal cord. The responses in distant DRGs are hard to reconcile with the limited
      damage to sensory neurons produced by the lesion. Inflammation of DRGs after
      spinal injury may contribute to hyper-reflexia and pain.

PMID- 15257148
TI  - Attentional deficit in dyslexia: a general or specific impairment?
AB  - Dyslexic and control children were tested in a visuomotor attentional task, which
      provides independent measures of the alerting, orienting and conflict components
      of the attentional system. Our results show that dyslexics are impaired with
      respect to controls in the attentional conflict component (resolution of conflict
      of incongruent peripheral information), while the alerting and orienting
      components remain preserved. It excludes an overall attentional impairment and
      points to more specific attentional processing difficulty i.e. distributed
      attention strategy. Generally, results of dyslexic boys are within the range of
      the control group, while reaction times of dyslexic girls are significantly
      slower than that of all other groups.

PMID- 15257149
TI  - Impaired brain development in the rat following prenatal exposure to
      methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution.
AB  - Several neuropsychiatric disorders, including schizophrenia, are the consequence
      of a disrupted development of the CNS. Accordingly, intrauterine exposure to
      toxins may increase the risk for psychopathology. We investigated whether
      prenatal exposure of rats to the neurotoxin methylazoxymethanol acetate led to
      long-term changes in cerebral neurotrophin levels. We measured the brain levels
      of nerve growth factor and brain derived neurotrophic factor in young adult and
      adult rats. Decreased nerve growth factor or brain derived neurotrophic factor
      were found in the parietal cortex accompanied by altered neurotrophin content in
      the hippocampus and entorhinal cortex. The present study is the first to show
      long-lasting effects of a single prenatal exposure to a neurotoxin on adult
      levels of neurotrophins in brain regions implicated in neuropsychiatric
      disorders.

PMID- 15257150
TI  - Down-regulation of p27kip1 increases proliferation of progenitor cells in adult
      rats.
AB  - Cyclin-dependent kinases (CDK) mediate the cell division cycle during G1 phase
      and CDK inhibitors negatively regulate the cell cycle. We investigated expression
      of the CDK inhibitor p27Kip1 and the effects of PI-3K/Akt on proliferation of
      progenitors in the subventricular zone of adult rat. Western blots and
      immunostaining revealed that 4 days after stroke, p27kip1 levels decreased and
      were absent in nuclei of the ipsilateral subventricular zone cells 7 days after
      stroke. Reduction in p27kip1 levels was concurrent with significant increases in
      BrdU immunoreactive cells in the subventricular zone. Treatment of stroke
      neurospheres with LY294002 significantly (p<0.05) reduced the numbers of
      neurospheres from 32 +/-5 in the stroke group to 14 +/- 3 in the stroke and
      LY294002 group. Collectively, our data suggest that stroke induced neural
      progenitor proliferation is mediated by down-regulation of p27Kip1 and activation
      of Akt.

PMID- 15257151
TI  - Dynamic zinc pools in mouse choroid plexus.
AB  - We examined the presence of Zn-transporters (ZnT1, ZnT3, ZnT4, and ZnT6) proteins
      and zinc ions in rat choroid epithelium with immunohistochemistry and zinc
      selenide autometallography (ZnSe(AMG)). The four ZnT proteins were all expressed
      in the choroid epithelial cells. ZnT3 immunostaining was found in vesicle
      membranes in the apical part of the cells, associated to the microvillus
      membrane. Correspondingly, the ZnSe(AMG) technique revealed zinc ions in small
      vesicles, in microvilli, and multivesicular bodies in the epithelial cells.
      Traceable zinc ions were also found in lysosome-like organelles of fenestrated
      endothelial cells, but here no corresponding ZnT3 immunostaining was seen. The
      observations suggests that the choroid plexus is instrumental to regulation of
      the level of zinc ions in the cerebrospinal fluid.

PMID- 15257152
TI  - Nigrostriatal dopamine release modulated by mesopontine muscarinic receptors.
AB  - The present study investigated the regulation of substantia nigra pars compacta
      (SNc) dopamine neuronal activity by pedunculopontine (PPT) cholinergic neurons.
      Changes in dopamine efflux following chemical activation or blockade of
      muscarinic acetylcholine receptors in the PPT were measured at stearate-carbon
      paste electrodes in the striatum of urethane (1.5 g/kg) anaesthetized male rats
      using in vivo chronoamperometry (30 s sampling rate). Intra-PPT infusions of a
      mixed muscarinic/nicotinic (carbachol 8 microg/microl) or M2/4-selective
      muscarinic (oxotremorine 0.5 microg/microl) receptor agonist attenuated striatal
      dopamine efflux, whereas a non-selective (scopolamine 100 microg/microl) or M2/4
      selective (methoctramine 50 microg/microl) muscarinic receptor antagonist
      enhanced striatal dopamine efflux. These results suggest that M2/4 muscarinic
      receptors in the mesopontine tonically influence SNc basal dopamine cell activity
      and striatal dopamine release.

PMID- 15257153
TI  - GABAA receptor gamma subunits in the prefrontal cortex of patients with
      schizophrenia and bipolar disorder.
AB  - Immunohistochemical and immunoblot techniques were employed in order to examine
      alterations of the GABAA receptor gamma subunits in the prefrontal cortex from
      postmortem subjects with schizophrenia and bipolar disorder.
      Immunohistochemically, gamma 1/3 immunolabeling in the neuronal soma in the
      prefrontal cortex from subjects with bipolar disorder was more intense than that
      of the controls and the subjects with schizophrenia. The intensity of gamma 1/3
      immunolabeling of the schizophrenic subjects was comparable with that of the
      controls. Immunoblot analysis demonstrated a significant increase in the gamma 1
      subunit in the bipolar subjects, whereas no remarkable difference was detected in
      the schizophrenic subjects. The present study suggests that the GABAA receptor
      gamma subunit is differentially involved in schizophrenia and bipolar disorder,
      and that the gamma subunit is up-regulated in the prefrontal cortex of subjects
      with bipolar disorder.

PMID- 15257154
TI  - Diazoxide and N omega-nitro-L-arginine counteracted A beta 1-42-induced
      cytotoxicity.
AB  - K(+) channel openers can activate K channels and have been shown to protect
      cultured neurons against excitotoxicity. Our study showed that diazoxide, a K(+)
      channel opener, could counteract the effects of A beta(1-42) and protect cells
      from A beta(1-42)-induced the increasing of mitochondrial membrane potential and
      the associated increase in intracellular reactive oxygen species levels; an
      inducible nitric oxide synthase inhibitor, N omega-nitro-L-arginine could protect
      cells from A beta(1-42)-induced the increasing of both mitochondrial membrane
      potential and intracellular reactive oxygen species levels. A 24 h exposure to A
      beta(1-42) did not result in apoptosis, suggesting that the increase in both
      mitochondrial membrane potential and reactive oxygen species levels preceded cell
      apoptosis or death.

PMID- 15257155
TI  - Incidental and intentional encoding in young and elderly adults.
AB  - Event-related potentials (ERPs) were recorded in young and elderly adults during
      the performance of an incidental encoding task (subjects were unexpectedly given
      a recognition test) followed by an intentional task (subjects expected the
      recognition test). Both tasks consisted of an encoding stage in which subjects
      classified words (natural/artificial) and a recognition stage in which they
      indicated whether the words were old (presented during the encoding stage) or
      new. In both groups and tasks, the ERPs, during encoding, differed as a function
      of subsequent recognition: the old words correctly recognized generated greater
      amplitude potentials than the incorrect ones. The memory processes expressed by
      these ERPs are preserved in elderly adults, independently of whether the
      information is incidentally or intentionally encoded.

PMID- 15257156
TI  - The neural basis of maternal responsiveness to infants: an fMRI study.
AB  - Using fMRI, we examined the neural correlates of maternal responsiveness. Ten
      healthy mothers viewed alternating blocks of video: (i) 40 s of their own infant;
      (ii) 20 s of a neutral video; (iii) 40 s of an unknown infant and (iv) 20 s of
      neutral video, repeated 4 times. Predominant BOLD signal change to the contrasts
      of infants minus neutral stimulus occurred in bilateral visual processing regions
      (BA 19,21,37,38); to own infant minus unknown infant in right anterior temporal
      pole (BA 38), left amygdala and visual cortex (BA 19), and to the unknown infant
      minus own infant contrast in bilateral orbitofrontal cortex (BA 10,47) and medial
      prefrontal cortex (BA 8) [corrected] These findings suggest that amygdala and
      temporal pole may be key sites in mediating a mother's response to her infant and
      reaffirms their importance in face emotion processing and social behaviour.

PMID- 15257157
TI  - Sleep changes produced by destruction of medial septal neurons in rats.
AB  - Changes in sleep-wakefulness were studied in male Wistar rats after destruction
      of the medial septal neurons with NMDA. Electroencephalogram, electromyogram and
      electrooculogram were recorded for 24 h prior to the destruction of the medial
      septum, and 7, 14 and 21 days after the destruction. There was a decrease in the
      total amount of slow wave sleep and frequency of slow wave sleep episodes after
      the lesion. It also produced an increase in the duration of paradoxical sleep
      episodes. These findings are in contrast to the changes produced after lesion of
      other basal forebrain areas. The present findings suggest that the medial septum
      may be involved in the genesis of slow wave sleep and inhibition of the durations
      of paradoxical sleep episodes.

PMID- 15257158
TI  - Induced gamma band responses: an early marker of memory encoding and retrieval.
AB  - Although mnemonic processes have been widely studied using event-related
      potentials (ERPs), memory-related oscillatory changes in the EEG have been
      relatively neglected. The aim of this study was to investigate memory encoding-
      and retrieval-related changes in the frequency domain. In particular, we focused
      on induced gamma band responses (GBRs), which are a candidate for the
      establishment and activation of widespread cell assemblies. At encoding, results
      revealed increased GBRs for subsequently recognised relative to subsequently
      forgotten items. At retrieval, recognised old stimuli were associated with higher
      GBRs compared to new stimuli. During encoding and retrieval GBR modulation
      preceded that of ERPs. Thus, GBRs might be a correlate of processes that onset
      earlier to those responsible for memory encoding and retrieval ERP effects.

PMID- 15257159
TI  - VALUE: to the heart of the matter.

PMID- 15257160
TI  - VALUE and supremacy of blood pressure control for cardiovascular protection.

PMID- 15257161
TI  - Mechanisms underlying the differential control of blood flow in the renal medulla
      and cortex.
AB  - There is much evidence that the medullary circulation plays a key role in
      regulating renal salt and water handling and, accordingly, the long-term level of
      arterial pressure. It has also recently become clear that various regulatory
      factors can affect medullary blood flow (MBF) differently from cortical blood
      flow (CBF). It appears likely that the influence of hormonal and neural factors
      on the control of arterial pressure is mediated partly through their impact on
      MBF. In this review, we focus on the mechanisms underlying the differential
      control of MBF and CBF, particularly the relative insensitivity of MBF to
      vasoconstrictors such as angiotensin II, endothelin-1 and the sympathetic nerves.
      The vascular architecture of the kidney appears to be arranged in a way that
      protects the renal medulla from ischaemic insults, with juxtamedullary
      arterioles, the source of MBF, having larger calibre than their counterparts in
      other kidney regions. Indeed, recent studies using vascular casting methodology
      suggest that juxtamedullary glomerular arterioles are not the chief regulators of
      MBF, which is consistent with the idea that outer medullary descending vasa recta
      play a key role in MBF control. Release of vasoactive paracrine factors such as
      nitric oxide and various eicosanoids from the vascular endothelium, and probably
      also from the tubular epithelium, appear to differentially modulate responses of
      MBF and CBF to hormonal and neural factors. The prevailing intrarenal hormonal
      milieu and existing haemodynamic conditions also appear to strongly modulate
      these responses, indicating that multiple control systems interact to regulate
      regional kidney blood flow at an integrative level.

PMID- 15257162
TI  - Old antihypertensives and new diabetes.
AB  - Diuretic antihypertensive therapy is recommended as first choice by many
      guidelines, often in combination with beta-blockers. However, such
      recommendations are based on relatively short-term trials, whereas treatment for
      hypertension is often a lifetime process. A meta-analysis of seven studies in
      58,010 individuals, showed that the 'new' therapies, namely angiotensin
      converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers
      (ARBs) and calcium channel blockers (CCBs) provoke less new diabetes than the
      conventional 'old' therapies (diuretics and beta-blockers). ACE inhibitors/ARBs
      decreased new diabetes by 20% (P < 0.001), whereas CCBs decreased new diabetes by
      16% (P < 0.001). The number needed to treat for approximately 4 years by new
      rather than old conventional therapy to avoid one case of new diabetes is about
      60-70. Other factors contributing to increased coronary risk are increased
      metabolic syndrome, blood lipid changes and hypokalaemia. It is not certain
      whether it is the new therapy that provides protection against new diabetes or
      the conventional therapy that precipitates new diabetes. However, when compared
      with placebo, ACE inhibition by ramipril or by the ARB, candesartan, both
      decrease the incidence of new diabetes, raising the hypothesis that these agents
      actually prevent the changes leading to insulin resistance, possibly by lessening
      the adverse effects of angiotensin II on the endothelium. Conversely, lipid
      abnormalities with conventional treatment could exert adverse effects on the
      endothelium. Therefore endothelial changes could help to explain the benefits of
      'modern' treatment compared with the defects of conventional therapy.

PMID- 15257163
TI  - Another benefit from salt intake reduction?

PMID- 15257164
TI  - Na+, kidney, hypertension and genes: lessons from rats.

PMID- 15257165
TI  - Central sympatholytic drugs for the treatment of hypertension: back to the
      future?

PMID- 15257166
TI  - A novel inhibitory role for CREG-mediated signalling in cardiac hypertrophy?

PMID- 15257167
TI  - The left atrium in hypertension: next to the chamber of power.

PMID- 15257168
TI  - Salt intake and Helicobacter pylori infection.
AB  - BACKGROUND: The chance finding of an association between Helicobacter pylori
      infection and hypertension and the known relationship between salt intake and
      blood pressure led us to speculate whether these two environmental factors might
      be related. A positive relationship between them might suggest that a high-salt
      diet could in some way facilitate gastric H. pylori infection. METHODS: We have
      therefore conducted an ecological study of the national H. pylori infection rates
      in the EUROGAST study and national salt excretion levels with the INTERSALT
      project. Ten nations were included in both projects. RESULTS: Statistically
      significant correlation between H. pylori infection rates and salt excretion were
      found in older men and women (r = 0.728 and r = 0.827, respectively) and in
      younger men (r = 0.728), but not younger women (r = 0.519). CONCLUSIONS: Our
      findings raise the possibility that salt intake may in some way facilitate H.
      pylori infection. A dedicated population survey is now justifiable to investigate
      the role of salt intake in H. pylori infection with the measurement of all
      possible confounding variables including particularly socio-economic status

PMID- 15257169
TI  - Trends in blood pressure levels, prevalence, awareness, treatment, and control of
      hypertension in the Czech population from 1985 to 2000/01.
AB  - OBJECTIVE: To assess trends in blood pressure (BP) levels, prevalence, awareness,
      and control of hypertension in the Czech population from 1985 to 2000/01. DESIGN:
      Five independent cross-sectional population surveys conducted in 1985, 1988,
      1992, 1997/98, and 2000/01. SETTING: Six, mostly rural, districts of the Czech
      Republic (Praha-vychod, Benesov, Pardubice, Chrudim, Cheb, and Jindrichuv
      Hradec). PARTICIPANTS: Men and women aged 25-64 years randomly selected from six
      districts using the National Population Register/General Health Insurance Company
      Register (covering, by law, all citizens). The total number of participants was
      11 726. MAIN OUTCOME MEASURES: We assessed the mean systolic BP, diastolic BP and
      pulse pressure, prevalence of hypertension (systolic BP > or = 140 mmHg and/or
      diastolic BP > or = 90 mmHg, or current treatment with antihypertensive drugs),
      awareness, treatment, and control of hypertension. RESULTS: Mean systolic BP,
      diastolic BP, and pulse pressure decreased significantly over a period of 15/16
      years. This was associated with a significant decrease in the prevalence of
      hypertension (from 47.1 to 39.1%, P < 0.001) and with an increase in its
      awareness (from 49.5 to 67.2%, P < 0.001), use of antihypertensive medication
      (from 29.3 to 49.3%, P < 0.001), and hypertension control (from 3.9 to 17.0%, P <
      0.001). Despite having lower BP values and prevalence of hypertension, females
      showed higher awareness of the disease, and were more frequently taking
      antihypertensive medication, and their hypertension was better controlled.
      CONCLUSION: The reduction in population BP and improved control of hypertension
      may have contributed to the decrease in cerebrovascular and coronary heart
      disease mortality in the Czech Republic. The positive longitudinal changes seen
      in the MONICA regions need not necessarily reflect the situation in the country
      as a whole. The situation is far from being optimal; a major problem is
      inadequate treatment of hypertension

PMID- 15257170
TI  - Identification of salt-sensitive genes in the kidneys of Dahl rats.
AB  - OBJECTIVE: Inherited differences in renal function underlie the effect of high
      salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl
      SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated
      by dietary sodium. METHODS: mRNA quantitation of both candidate genes implicated
      in sodium excretion and anonymous gene products found by differential
      hybridization in the kidneys of salt-resistant (SR) and salt sensitive (SS)
      inbred Dahl rats on high and low salt diets for 21 days. RESULTS: Differential
      screening revealed a cDNA clone (H1) that showed increased dietary salt-dependent
      expression only in SS rats. Sequencing of the H1 cDNA showed it was the Dahl rat
      homologue to a perchloric acid soluble protein expressed in liver and kidney.
      Among candidate genes, transcript levels of arginosuccinate synthetase (AS) and
      arginosuccinate lyase (AL) were higher in SS on low salt diets, and AS mRNA
      increased in response to a high salt diet in SR. Renal mRNA for the ANP-A and the
      vasopressin type II receptors did not differ by strain or dietary conditions.
      CONCLUSIONS: Three new salt-sensitive genes were detected in the kidneys of
      inbred Dahl rats. Two genes encode enzymes in the biosynthesis of L-arginine. The
      upregulation of these genes by dietary salt indicates increased demand and
      biosynthesis of L-arginine in Dahl SS rats. A third gene encodes a small acid
      soluble protein thought to influence the transcription/translation of numerous
      genes. Further studies will be needed to determine the nature of the association
      of these genes with salt-sensitivity and blood pressure.

PMID- 15257171
TI  - Dissecting quantitative trait loci into opposite blood pressure effects on Dahl
      rat chromosome 8 by congenic strains.
AB  - OBJECTIVE: Our previous linkage analyses showed that there was likely a
      quantitative trait locus (QTL) for blood pressure (BP) on chromosome 8 (Chr 8) in
      the strain comparison between the Dahl salt-sensitive (S) and the Lewis (LEW)
      rats. The current work is to delineate the chromosome interval harboring this QTL
      by using congenic strains with different chromosome substitutions. METHODS: Two
      congenic strains were produced by replacing different segments of the S rats with
      the homologous segments of the LEW rats. A genome-wide marker screening was
      utilized to accelerate this process. The two strains generated are designated as
      C8S.L1 and C8S.L2, respectively. BPs of the rats were measured by telemetry.
      RESULTS: C8S.L1 showed a BP lower than that of S rats. In contrast, C8S.L2 did
      not have chromosome overlaps with C8S.L1, but unexpectedly, exhibited a BP
      raising effect, higher than that of S rats. CONCLUSION: There are at least two
      QTLs present in a section of Chr 8 that possess opposite BP effects. The current
      congenic work reveals not only the presence of QTLs, but the complexity of QTLs
      on BP. The novel congenic strain with hypertension more severe than S provides a
      new model for studies in elucidating physiological mechanisms controlling BP.

PMID- 15257172
TI  - The S447X polymorphism of the lipoprotein lipase gene is associated with
      lipoprotein lipid and blood pressure levels in Chinese patients with essential
      hypertension.
AB  - OBJECTIVE: To investigate the association between the S447X polymorphism of the
      lipoprotein lipase (LPL) gene and lipoprotein lipid and blood pressure (BP)
      levels in 904 Chinese subjects with essential hypertension. METHOD: Five hundred
      and sixty-three male and 341 female patients (aged 35-69 years) were randomly
      selected from hypertensive patients diagnosed in the Community-based
      Comprehensive Studies on Prevention and Control of Hypertension Project in China
      (CCPACH) and not treated with antihypertensive medications for at least 2 weeks
      immediately before blood collection. RESULTS: After multivariate adjustment for
      age, body mass index (BMI), smoking status, alcohol intake and serum glucose, the
      X447 allele was significantly associated with low triglyceride, log triglyceride
      : high-density lipoprotein (HDL)-cholesterol ratio and high HDL-cholesterol
      levels compared with the S447S genotype, but not with BP levels in the whole
      study population. However, upon stratification for dyslipidemic status, the X447
      allele was associated with higher systolic blood pressure (SBP) (P < 0.05) and
      pulse pressure (PP) (P < 0.05) compared with the S447S genotype after
      multivariate adjustment in dyslipidemic subjects, but not in those without
      dyslipidemia. A statistically significant interaction between the LPL S447X
      polymorphism and dyslipidemic status was observed for SBP and PP levels,
      suggesting that dyslipidemic status might modify the effect of the LPL S447X
      polymorphism on BP levels. CONCLUSIONS: Our findings suggest that a high
      concentration of triglyceride and/or low concentration of HDL-cholesterol are
      associated with high SBP and PP in hypertensive patients with the X447 allele of
      the LPL gene.

PMID- 15257173
TI  - Genetic susceptibility loci for essential hypertension and blood pressure on
      chromosome 17 in 147 Chinese pedigrees.
AB  - OBJECTIVES: We scanned human chromosome 17 to verify previous studies on the
      chromosome as well as to explore possible new loci of essential hypertension in a
      Chinese Han population. METHODS: A genomic scan of chromosome 17 with 15
      microsatellite markers was conducted in a total of 757 individuals from 147
      Chinese hypertension pedigrees. We used three softwares to analyse hypertension
      as a qualitative trait and blood pressure as quantitative phenotypes linkage
      analyses in the North group (406 individuals from 78 northern families), the
      South group (351 individuals from 69 southern families) and the combined group of
      the Chinese population separately. RESULTS: For qualitative trait, a 7-cM
      (centiMorgan) interval flanked by D17S831 (7 cM) and D17S938 (15 cM) showed
      suggestive linkage results (P < 0.00074) in the southern population by
      SAGE/SIBPAL2. For blood pressure (BP) quantitative phenotypes, the regions with
      lowest P values in SAGE and highest logarithm of odds (LOD) scores in SOLAR just
      overlapped this 7-cM interval in the South group for both systolic blood pressure
      (SBP) and diastolic blood pressure (DBP), though these peaks did not yet reach to
      the suggestive linkage criteria (P = 0.00074, LOD score = 2.2). In the northern
      population, in a region around 75.0 cM (D17S787) a peak was found with non
      parametric-linkage (NPL) score 1.82 for qualitative trait using GENEHUNTER.
      CONCLUSIONS: In the southern population of China, our results demonstrate that a
      7-cM interval region flanked by D17S831 (7 cM) and D17S938 (15 cM) is
      suggestively linked with hypertension.

PMID- 15257174
TI  - The role of adenosine-related genes variants in susceptibility to essential
      hypertension.
AB  - OBJECTIVE: To test markers within adenosine-related genes: A1 and A2a receptors
      (ADORA1, ADORA2a) and adenosine deaminase (ADA) for potential involvement in
      essential hypertension (EH). DESIGN: Case-control association study investigating
      gene variants for the ADORA1, ADORA2a and ADA genes. PARTICIPANTS: The study used
      a cohort of 249 unrelated hypertensive individuals who were diagnosed with
      hypertension, and an age, sex and ethnically matched group of 249 normotensive
      controls. RESULTS: The association analysis indicated that both allele and
      genotype frequencies did not differ significantly between the case and control
      groups (P > 0.05) for any of the markers tested. CONCLUSION: The adenosine
      related gene variants do not appear to alter susceptibility to the disease in
      this group of essential hypertensives. However, involvement of these genes and
      the adenosine system cannot be conclusively excluded from essential hypertension
      pathogenesis as other gene variants may still be involved.

PMID- 15257175
TI  - CD14 C(-260)T gene polymorphism, circulating soluble CD14 levels and
      arteriosclerosis.
AB  - BACKGROUND: CD14 pathway is at the crossroads between infection and inflammation.
      In human pathology, divergent results have been reported on the relationship
      between a polymorphism in the promoter of receptor CD14 (C260T), expression of
      soluble CD14 (sCD14) receptor and atherosclerosis. The aim of the study was to
      investigate in a cross-sectional population-based sample the relationships
      between C260T polymorphism in CD14 gene, sCD14 blood levels and arterial wall.
      METHODS: Among 1015 subjects, randomly recruited by the Toulouse MONICA center
      between 1995 and 1997, 899 subjects with complete data for all the measurements,
      were analyzed. sCD14 was measured using an immuno-enzymatic method. Common
      carotid intima-media thickness (IMT) and the presence of plaques in the carotid
      and femoral arteries were assessed by ultrasonography. A genotypic examination
      for the CD14 C260T polymorphism was performed. RESULTS: An increase in sCD14
      expression was observed in subjects carrying t allele (P < 0.01). No significant
      difference in intima-media thickness, number of plaques and pulse wave velocity
      was noticed according to C260T polymorphism. An interaction (P < 0.05) was
      observed between C260T polymorphism and current smoking in sCD14 expression:
      among smokers, no significant change in sCD14 was observed in individuals
      carrying t allele. CONCLUSION: Although (C260T) polymorphism in CD14 gene in this
      study is associated with expression of sCD14, no significant association was
      found between this polymorphism and early markers of atherosclerosis. This
      polymorphism affects plasma levels of sCD14 in relation to current smoking
      status. Further studies are needed to determine whether this interaction
      influences the deleterious effect of smoking on vascular events.

PMID- 15257176
TI  - Rilmenidine sympatholytic activity preserves mental stress, orthostatic
      sympathetic responses and adrenaline secretion.
AB  - BACKGROUND: Heightened central sympathetic nervous outflow is common in essential
      hypertension, contributing to hypertension development and possibly also to
      complications. Acute sympathetic nervous activation is a proven trigger for
      adverse cardiovascular events. Accordingly, antihypertensive drugs inhibiting
      sympathetic outflow represent a theoretically attractive therapeutic option.
      OBJECTIVES: To study the sympatholytic and blood pressure-lowering activity of
      the imidazoline binding agent rilmenidine at rest and during reflex sympathetic
      activation. DESIGN AND METHODS: We used a randomized, double-blind, 6-week cross
      over study, with a 1-week placebo run-in period, two 2-week active treatment
      intervals (rilmenidine 1 mg twice daily or placebo) and intervening 1-week
      placebo washout. In 15 hypertensive patients, noradrenaline and adrenaline plasma
      kinetics and intra-arterial blood pressure measurements were performed at rest,
      after mental stress (difficult mental arithmetic) and during head-up tilting, at
      the end of the 2-week dosing periods. RESULTS: The noradrenaline spillover rate,
      indicative of whole body sympathetic activity, was reduced 35% by rilmenidine at
      rest (P < 0.01) and remained significantly lower during mental stress and
      tilting, although the increases in noradrenaline spillover with both stimuli were
      preserved. The effects on intra-arterial blood pressure ran in parallel, a fall
      in supine resting pressure, but no reduction in blood pressure rise during mental
      stress and a lack of fall in blood pressure with tilting. On placebo, adrenaline
      secretion was 0.88 +/- 0.15 nmol/min (mean +/- SE) at rest, increased by 0.42 +/-
      0.23 nmol/min with mental stress (P = 0.019) and was unchanged with tilting.
      Rilmenidine left adrenaline secretion untouched under all conditions.
      CONCLUSIONS: The present study confirms a sympatholytic effect of rilmenidine
      during supine rest but preservation of sympathetic responses during mental stress
      and tilting, with the latter underlying a freedom from postural hypotension on
      the drug. The absence of suppression of reflexive sympathetic responses contrasts
      with the described effects of rilmenidine in experimental animals, and emphasizes
      the previously demonstrated unique importance in humans of suprabulbar
      noradrenergic neuronal projections from the brainstem in regulating tonic
      sympathetic activity, with these being inhibited by imidazoline binding agents.
      Sympathetic nervous inhibition with rilmenidine contrasted with an absence of
      suppression of adrenaline secretion, affirming that sympathetic nervous and
      adrenal medullary function can be disconnected.

PMID- 15257177
TI  - Altered profile of baroreflex and autonomic responses to lower body negative
      pressure in chronic orthostatic intolerance.
AB  - BACKGROUND: Chronic orthostatic intolerance (COI) is a common and disabling
      autonomic syndrome of unclear pathophysiology. We tested the hypothesis that
      baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40
      mmHg) could be altered in COI patients. METHODS: Electrocardiogram (ECG), non
      invasive arterial blood pressure and respiratory activity were measured during
      progressive LBNP (seven patients and seven volunteers). Lumped arterial
      baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary
      components, were assessed by multivariate closed-loop analysis of RR interval and
      systolic arterial pressure (SAP) spontaneous variabilities and respiration.
      Monovariate spectral analysis of RR interval and SAP variability provided markers
      of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic
      modulation. RESULTS: Similar reductions in overall and cardiopulmonary baroreflex
      gain were observed in both groups in response to graded LBNP. In contrast, only
      controls demonstrated a selective increase in arterial baroreflex sensitivity, at
      low-grade LBNP. Clear increases in the low-frequency component of RR interval
      variability (LFRR) [and decreases in the high-frequency component of RR interval
      variability (HFRR), both in normalized units] were observed in controls with
      graded LBNP, while insignificant changes occurred in COI patients, who showed,
      conversely, exaggerated sympathetic vasomotor responses [as assessed by the low
      frequency component of SAP variability (LFSAP)]. CONCLUSIONS: Patients with
      chronic orthostatic intolerance show distinct signs of altered baroreflex and
      autonomic regulation of the SA node and of the vasculature in response to graded
      LBNP.

PMID- 15257178
TI  - Impact of current and past blood pressure on retinal arteriolar diameter in an
      older population.
AB  - OBJECTIVE: To examine the effects of current and past blood pressure on retinal
      arteriolar diameter in a general older population. DESIGN: Cross-sectional and
      longitudinal studies. SETTING: Population-based cohort study of older residents
      from an area west of Sydney, Australia. PARTICIPANTS: Two thousand three hundred
      and thirty-five individuals (n = 2335) (aged > or = 54 years) who attended the 5
      year follow-up Blue Mountains Eye Study during 1997-99. MAIN OUTCOME MEASURES: A
      computer-assisted method measured vessel diameters from digitized right eye
      retinal photographs. The narrowest quintile of central retinal arteriolar
      equivalent or arteriole-to-venule ratio (AVR) defined generalized arteriolar
      narrowing. Blood pressure was measured using a mercury sphygmomanometer. RESULTS:
      After simultaneous adjustment for age, sex, body mass index, smoking and current
      or past blood pressure, elevated levels of both current and past blood pressure
      were associated with narrower retinal arterioles [Ptrend = 0.009 and 0.007 for
      current and past systolic blood pressure (SBP), respectively] and lower AVR
      [Ptrend = 0.001 and 0.0009 for current and past diastolic blood pressure (DBP),
      respectively]. Generalized arteriolar narrowing was associated with both current
      blood pressure [adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5
      3.8 for the highest versus lowest quintile of current DBP] and past blood
      pressure (adjusted OR 1.7, 95% CI 1.1-2.6, for the highest versus lowest quintile
      of past DBP). Hypertension duration or control status at baseline had no
      additional effect on arteriolar diameter after adjusting for current blood
      pressure. CONCLUSIONS: Our data document the independent effects of both current
      and past blood pressure on small vessel calibre in the retina, suggesting that
      retinal arteriolar narrowing may result from the cumulative effects of long
      standing hypertension.

PMID- 15257180
TI  - Role of nitric oxide pathway in hypotensive and renal effects of furosemide
      during extracellular volume expansion.
AB  - OBJECTIVE: In previous studies we demonstrated that the administration of
      furosemide associated with L-arginine contributes to enhanced hypotension and
      induces greater water than electrolyte excretion, in both normal and expansion
      conditions. The aim of the present study was to elucidate the interaction between
      furosemide and the nitric oxide (NO) system in renal and vascular responses
      during extracellular volume expansion. DESIGN AND METHODS: Expanded [10% body
      weight (bw)] and non-expanded anaesthetized male Wistar rats were treated with
      furosemide (7.5 mg/kg bw). Mean arterial pressure, nitrite and nitrate excretion
      (NOx) were determined. NADPH-diaphorase activity, a marker of nitric oxide
      synthase (NOS) activity, was measured histochemically in different segments of
      the nephron, aorta and renal arteries. NOS activity was determined using an L
      [U14C]-arginine substrate in the kidney and aorta of expanded and non-expanded
      rats, in basal conditions and after furosemide (10 micromol/l). RESULTS: The
      hypotensive effect of furosemide was enhanced when NO production was stimulated
      in expanded and non-expanded animals. The diuretic treatment induced a
      significant increase in NOx excretion, in NADPH-diaphorase activity in the thick
      ascending limb of Henle, renal arteries and aorta, and in NOS activity in aorta
      and kidney in both groups. CONCLUSIONS: Our results suggest that the hypotensive
      effect of furosemide may be attributed to NO-mediated vasodilation. The enhanced
      NOS activity, observed in the renal artery of furosemide-treated rats, could
      explain the increased renal plasma flow induced by furosemide. In addition, NO
      pathway stimulation in the kidney could be one of the mechanisms by which
      furosemide exerts its diuretic and natriuretic effects, in control and in
      expansion conditions.

PMID- 15257179
TI  - Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced
      hypertension.
AB  - OBJECTIVE: Red wine polyphenols have been reported to possess beneficial
      properties for preventing cardiovascular diseases but their effects on
      hemodynamic and functional cardiovascular changes during inhibition of nitric
      oxide (NO) synthesis have not been elucidated. DESIGN: The effects of the red
      wine polyphenols, Provinols, on arterial hypertension as well as left ventricular
      (LV) hypertrophy, myocardial fibrosis and vascular remodeling were investigated
      in rats during chronic inhibition of nitric oxide synthase (NOS) activity. Rats
      were divided into four groups: a control group, a group treated with N-nitro-L
      arginine methyl ester (L-NAME) (40 mg/kg per day), a group receiving Provinols
      (40 mg/kg per day) alone or Provinols plus L-NAME. RESULTS: Provinols markedly
      reduced the increase in both blood pressure and protein synthesis in the heart
      and aorta caused by chronic inhibition of NO synthesis. Provinols reduced
      myocardial fibrosis even though it did not affect LV hypertrophy. In addition,
      Provinols prevented aortic thickening and corrected the augmented reactivity of
      the aorta to norepinephrine and the attenuated endothelium-dependent relaxation
      to acetylcholine in NO-deficient rats. These alterations were associated with an
      increase of NOS activity, a moderate enhancement of endothelial NOS expression
      and a reduction of oxidative stress in the LV and aorta. CONCLUSION: Our results
      provide evidence that Provinols partially prevents L-NAME-induced hypertension,
      cardiovascular remodeling and vascular dysfunction via the increase of NO
      synthase activity and prevention of oxidative stress. Thus, the beneficial
      effects of plant polyphenols in prevention of hypertension may result from their
      complex influence on the NO balance in the cardiovascular system.

PMID- 15257181
TI  - Renal nitric oxide production is decreased in diabetic rats and improved by AT1
      receptor blockade.
AB  - OBJECTIVE: Diabetes mellitus is associated with increased incidence of
      cardiovascular complications. Lack of nitric oxide production may exacerbate
      these complications. We hypothesized that diabetes decreases renal nitric oxide
      (NO) production, an effect that is reversed via inhibition of angiotensin subtype
      1 receptor. METHODS: We monitored changes in renal interstitial fluid nitric
      oxide by a microdialysis technique in the renal cortex of conscious Sprague
      Dawley rats. Rats (n = 8 each group) were given streptozotocin 30 mg/kg
      intravenously to induce diabetes. Changes in renal interstitial fluid angiotensin
      II and NO were evaluated at baseline before and over 12 weeks during the
      development of diabetes and at 4 and 8 h after oral administration of the
      angiotensin subtype-1 (AT1) receptor blockers, losartan (30 mg/kg) or valsartan
      (10 mg/kg). RESULTS: Renal interstitial fluid angiotensin II significantly
      increased after development of diabetes. In contrast, basal renal interstitial
      fluid nitric oxide decreased significantly over 12 weeks after development of
      diabetes. Both losartan and valsartan caused a further increase in renal
      angiotensin II levels. Some 4 h after administration, there was significantly
      greater increase in renal nitric oxide after administration of valsartan than of
      losartan. At 8 h post- treatment, only valsartan caused a significant increase in
      renal nitric oxide levels. CONCLUSION: These results demonstrate that diabetes
      mellitus is associated with an increase in renal production of angiotensin II,
      while renal production of nitric oxide is reduced. The decrease in renal NO is
      reversed by AT1 receptor blockade.

PMID- 15257182
TI  - CREG, a new regulator of ERK1/2 in cardiac hypertrophy.
AB  - OBJECTIVES: The cellular repressor of E1A-stimulated genes (CREG), a mannose-6
      phosphate-containing secreted glycoprotein, enhances differentiation and inhibits
      proliferation. In this study, our aim was to understand the role of CREG in
      cardiac hypertrophy. METHODS: Two models of cardiac hypertrophy were used: the in
      vivo pressure-overloaded rat cardiac hypertrophy and the in vitro stretched
      neonatal rat cardiomyocyte hypertrophy. CREG's function in cardiac cells was
      investigated after over-expression or antisense inhibition of CREG. RESULTS: We
      found reduced CREG expression in rat hearts after the in vivo overload, as shown
      by Northern blot analysis. CREG over-expression inhibited cardiac cell growth, as
      demonstrated by reduced protein content, cell area and ERK1/2 level in cultured
      neonatal rat cardiomyocytes, and by the reduced proliferation of cultured
      neonatal rat cardiac fibroblasts. Additionally, over-expression of CREG dampened
      the stretched cardiomyocyte hypertrophy through ERK1/2. On the other hand, the
      opposite effects were observed when CREG expression was decreased using
      antisense. This modulation of CREG expression resulted in no changes in the
      cardiomyocyte expressions of the hypertrophic or apoptotic signaling molecules
      such as protein kinase C (PKC) epsilon, PKC beta1, PKC alpha, PKC beta2, PKC
      delta, JNK1/2, p38, p53, Bax, Bcl2 and Fas. CONCLUSIONS: CREG was found to
      inhibit cardiac cell growth as a novel regulator of ERK1/2 and might participate
      in the development of cardiac hypertrophy under pressure overload. The insight
      that CREG inhibited the growth in rat hearts in vivo and in cardiac cells in
      vitro provides new clues for further investigation of the mechanism of heart
      remodeling.

PMID- 15257183
TI  - Relationship between left ventricular geometry and left atrial size and function
      in patients with systemic hypertension.
AB  - BACKGROUND: Arterial hypertension determines distinct adaptive left ventricular
      geometric responses, which may differently affect left ventricular function and
      left atrial performance. OBJECTIVES: In this study, the effect of left
      ventricular geometry on left atrial size and function, and the relationship
      between left atrial size and left ventricular mass were assessed in 336 patients
      with systemic arterial hypertension who had undergone Doppler echocardiography.
      METHODS AND RESULTS: Patients were classified into concentric (110 patients with
      concentric left ventricular geometry defined as relative wall thickness > or =
      0.44) and eccentric groups (226 patients with relative wall thickness < 0.44).
      Comparison to the latter, the former had greater left atrial size, left atrial
      ejection force, left ventricular mass and lower left ventricular midwall
      fractional shortening. Left ventricular concentric, rather than eccentric,
      geometry emerged by multivariate analysis as a factor independently associated
      with the highest degree of left atrial ejection force. Left atrial size was
      positively related to left ventricular mass in the whole population (r = 0.65,
      SEE = 6 ml, P < 0.00001). This relationship was maintained in the subgroups with
      concentric (r = 0.65, SEE = 6 ml, P < 0.00001) or eccentric geometry (r = 0.59,
      SEE = 6 ml, P < 0.00001). CONCLUSIONS: Our results indicate that the relationship
      of left ventricular geometry to both left atrial size and ejection force in
      hypertensive patients is relevant. Concentric left ventricular geometry is
      associated with greater left atrial size and ejection force than eccentric
      geometry, suggesting that increased left ventricular stiffness has a greater
      effect in stimulating left atrial performance than left ventricular end-systolic
      stress. The degree of left atrial enlargement similarly depends on left
      ventricular mass in patients with concentric and eccentric geometry.

PMID- 15257184
TI  - N-terminal pro-brain natriuretic peptide predicts cardiovascular events in
      patients with hypertension and left ventricular hypertrophy: a LIFE study.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and N-terminal
      pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers
      in patients with chronic heart failure, as well as in the general population. We
      investigated whether high Nt-proBNP or Nt-proANP could also predict the composite
      endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial
      infarction in patients with hypertension and left ventricular (LV) hypertrophy.
      METHODS: After 2 weeks of placebo treatment, clinical, laboratory and
      echocardiographic variables were assessed in 183 hypertensive participants in the
      LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP and Nt
      proANP were measured by immunoassay at baseline. The patients were followed for
      60 +/- 5 months. RESULTS: Using Cox regression analysis, the 25 CEP were
      predicted by ln(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01)
      as well as ln(Nt-proANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the
      median value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6
      versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with
      higher incidence of CEP in the 123 patients without history of diabetes or
      cardiovascular disease (14.8 versus 4.3%, P < 0.05), but the association was
      insignificant in the 60 patients with a history of diabetes or cardiovascular
      disease (26.3 versus 18.2%, NS). Nt-proANP showed the same tendency. CONCLUSION:
      Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in
      patients with hypertension and LV hypertrophy, especially in patients without
      diabetes or clinically overt cardiovascular disease.

PMID- 15257185
TI  - The Study on COgnition and Prognosis in the Elderly (SCOPE); outcomes in patients
      not receiving add-on therapy after randomization.
AB  - OBJECTIVE: To assess clinical outcomes in the Study on COgnition and Prognosis in
      the Elderly (SCOPE) in patients who did not receive add-on antihypertensive
      therapy after randomization, i.e. in patients that best reflect the original
      intention of a placebo-controlled trial. DESIGN: Post-hoc analysis of a
      prospective, randomized, controlled trial. SETTINGS AND PARTICIPANTS: Five
      hundred and twenty-seven centres in 15 countries participated in SCOPE. Patients
      aged 70-89 years, with systolic blood pressure 160-179 mmHg and/or diastolic
      blood pressure 90-99 mmHg, and preserved cognitive function were eligible. Out of
      4937 patients in SCOPE, 2098 did not receive add-on therapy. INTERVENTION: The
      number of patients who received candesartan 8-16 mg once daily was 1253, and 845
      received placebo. Mean follow-up was 3.7 and 3.5 years, respectively. MAIN
      OUTCOME MEASURES: Primary: major cardiovascular events (cardiovascular mortality,
      non-fatal stroke or non-fatal myocardial infarction). Secondary: total mortality,
      cardiovascular mortality, fatal and non-fatal myocardial infarction, fatal and
      non-fatal stroke, cognitive function, and dementia. RESULTS: The treatment groups
      were generally well balanced for baseline characteristics. Blood pressure fell by
      21.8/11.0 mmHg in the candesartan group and by 17.2/8.4 mmHg in the placebo
      group. There were significant relative risk reductions with candesartan in major
      cardiovascular events (32%, P = 0.013), cardiovascular mortality (29%, P =
      0.049), and total mortality (27%, P = 0.018). There were no significant
      differences between the treatment groups in cognitive outcomes. Both treatments
      were generally well tolerated. CONCLUSIONS: Treatment of elderly patients with
      mild hypertension is beneficial and supports current recommendations. Candesartan
      appears an appropriate therapy in such patients, in view of its favourable
      tolerability profile and ability to reduce major cardiovascular events.

PMID- 15257186
TI  - Equivalence of indapamide SR and enalapril on microalbuminuria reduction in
      hypertensive patients with type 2 diabetes: the NESTOR Study.
AB  - OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and
      hypertension is primarily dependent on the severity of hypertension, and to
      compare the effectiveness of two antihypertensive drugs with opposite effects on
      the renin-angiotensin system [the diuretic, indapamide sustained release (SR),
      and an angiotensin-converting enzyme inhibitor, enalapril] in reducing
      microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind,
      double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a
      4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men)
      with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140
      180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent
      microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive
      indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day.
      Amlodipine, atenolol, or both were added, if necessary, to achieve the target
      blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the
      urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence
      interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and
      enalapril groups, respectively. Equivalence was demonstrated between the two
      groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial
      pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/-
      9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly
      greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group
      required additional antihypertensive therapy, with no differences between groups.
      Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is
      equivalent to enalapril-based therapy in reducing microalbuminuria with effective
      blood pressure reduction in patients with hypertension and type 2 diabetes.

PMID- 15257187
TI  - Selective reduction of cardiac mass and central blood pressure on low-dose
      combination perindopril/indapamide in hypertensive subjects.
AB  - OBJECTIVE: In hypertension, blockade of the renin-angiotensin system reduces left
      ventricular mass (LVM) independently of brachial systolic (S), diastolic (D), and
      mean (M) blood pressure (BP). From central to peripheral arteries, MBP and DBP
      are practically unchanged, whereas SBP and pulse pressure (PP) increase
      significantly. The objective was to determine whether changes in LVM under drug
      treatment was preferentially associated with changes in central or brachial SBP
      and PP. DESIGN: A substudy of 146 subjects was selected from 469 hypertensive
      patients submitted to a double-blind randomized trial comparing the combination
      of perindopril (2 mg; Per) and indapamide (0.625 mg; Ind) with atenolol (50 mg,
      one tablet per day). MAIN OUTCOME MEASURES: Before and after 1 year of treatment:
      LVM (echocardiography) in 146 subjects and, in 52 of them, central (carotid) BP
      and timing of wave reflections (tonometry). RESULTS: LVM changes were
      significantly associated with antihypertensive treatment, with lower LVM with
      Per/Ind than with atenolol. Changes in SBP and PP, but not in MBP and DBP, were
      more significantly associated with Per/Ind than with atenolol, with more
      pronounced effects using central than brachial measurements, and a longer delay
      in central return of wave reflections under Per/Ind. In the sampling of 52
      patients with tonometry, the change in LVM between the two drug regimens was
      significantly linked to central, but not brachial, PP change. CONCLUSIONS: This
      observational study shows a lower LVM under Per/Ind than under atenolol. The
      greater change in LVM on Per/Ind was linked to central and not brachial blood
      pressure.

PMID- 15257188
TI  - Design of the Syst-Eur trial and Syst-Eur Phase 2: Thomas Weihrauch's
      contributions.

PMID- 15257189
TI  - Pulse waveform analysis and arterial stiffness: realism can replace evangelism
      and scepticism.

PMID- 15257205
TI  - Determination of cardiac output with multislice spiral computed tomography: a
      validation study.
AB  - OBJECTIVE: To validate and to determine the reproducibility of cardiac output
      (CO) measurements based on a test-bolus examination in multislice spiral computed
      tomography (MSCT) in comparison with invasively measured CO using the thermal
      dilution technique. MATERIAL AND METHODS: In 8 swine, CO was determined by
      invasive thermal dilution technique and by analysis of enhancement data from
      dynamic MSCT test-bolus examinations. To assess reproducibility, all MSCT
      examinations were performed twice. Results were compared using Pearson's
      correlation coefficient and Bland-Altman plots. RESULTS: Measure by thermal
      dilution technique CO was 3.71 +/- 1.12 L/min, whereas CO was 3.67 +/- 1.30 L/min
      using MSCT. Pearson's correlation coefficient was 0.89. The average deviation
      between MSCT and thermal dilution technique was 0.04 L/min with a standard
      deviation of 0.59 L/min. There was a good agreement between both MSCT
      measurements with a mean deviation of -0.03 L/min and a standard deviation of
      0.51 L/min. CONCLUSION: CO can reliably be determined from MSCT by means of
      indicator dilution technique. Measurements are reproducible and provide valuable
      information on the overall cardiovascular performance without application of
      additional contrast material or radiation. As this technique does not require
      time-consuming postprocessing it can be added to routine reporting.

PMID- 15257206
TI  - Comparison of cellular mechanisms underlying histamine release from rat mast
      cells induced by ionic and nonionic radiographic contrast media.
AB  - PURPOSE: To determine the cellular mechanisms underlying mast cell histamine
      release induced by ionic and nonionic radiographic contrast media. MATERIALS AND
      METHODS: Histamine release from rat pulmonary mast cells was measured after
      incubation with various radiographic contrast media. The cellular cAMP content
      was determined by an enzymatic immunoassay. RESULTS: Both ionic and nonionic
      contrast media stimulated the histamine release, although the former was more
      potent than the latter. Dibutyryl cAMP suppressed histamine release evoked by
      ionic but not nonionic contrast media in a manner dependent on A kinase. The
      cellular cAMP content was lowered only by ionic contrast media. However, a
      secretory phospholipase A2 inhibitor p-bromophenacyl bromide inhibited both ionic
      and nonionic contrast media-evoked histamine releases. CONCLUSION: We
      demonstrated for the first time the difference and similarity in the cellular
      mechanisms underlying histamine release induced by ionic and nonionic contrast
      media, in which the reduction in cAMP was specific for ionic materials and the
      activation of secretory phospholipase A2 may be common to both agents.

PMID- 15257207
TI  - Analysis of cerebral infarction pattern in computed tomography images of patients
      with internal carotid artery stenosis.
AB  - RATIONALE AND OBJECTIVES: An unbiased and quantitative analysis of lesion
      patterns in patient groups is described and applied to the analysis of infarction
      patterns. MATERIALS AND METHODS: One hundred forty-two computed tomographic
      images of patients with ischemic stroke were registered to an average computed
      tomographic brain image, which was used as template. Lesions were segmented
      manually and averaged per category of internal carotid artery (ICA) stenosis.
      Thus, patterns of lesion distribution were formed. Differences then were analyzed
      using nonparametric statistics. This analysis was compared with the traditional
      classification of lesions. RESULTS: The nonparametric analysis showed an
      increased involvement of the territory of the middle cerebral artery in
      infarctions in patients with ICA occlusion compared with patients with mild or
      severe ICA stenosis. These differences did not show when classification of
      infarctions was used. CONCLUSIONS: The presented method is more sensitive to
      differences in lesion patterns than traditional lesion classification and showed
      a different infarction pattern for ICA occlusion.

PMID- 15257208
TI  - High in-plane resolution T2-weighted magnetic resonance imaging of acute
      myocardial ischemia in pigs using the intravascular contrast agent NC100150
      injection.
AB  - RATIONALE AND OBJECTIVES: The intravascular contrast agent NC100150 injection was
      tested for its ability to demarcate nonperfused myocardium in a porcine model of
      coronary occlusion. MATERIALS AND METHODS: A T2-weighted fast spin echo sequence
      was acquired ex vivo and in vivo during first pass and steady-state circulation
      of the contrast agent in 2 dosages (2 and 5 mg Fe/kg bw) or saline. RESULTS: Ex
      vivo, in the high-dose group, the volume of nonperfused myocardium determined
      from T2-weighted images was 99% of that determined from photographs where
      perfused myocardium stained with fluorescein. A significantly higher contrast to
      noise ratio between perfused and nonperfused myocardium was found (both ex and in
      vivo in steady state) compared with the control group. During first pass, a
      significant reduction in signal intensity (74 +/- 18%) was found in perfused
      myocardium after contrast injection. CONCLUSION: NC100150 injection, combined
      with T2-weighted turbo spin echo imaging, allowed detailed visualization of non
      perfused myocardium in the steady state, which corresponded to the area at risk
      as determined by fluorescein.

PMID- 15257209
TI  - In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining
      R1 in steady state after the administration of the intravascular contrast agent
      NC100150 injection.
AB  - RATIONALE AND OBJECTIVES: To study the dose response in perfused and nonperfused
      myocardium by measuring relaxation rate (R1) in a steady-state situation after
      injection of the intravascular contrast agent NC100150 Injection in pigs and
      whether the dose response differs in vivo and ex vivo. MATERIALS AND METHODS: The
      left anterior descending artery was occluded. R1 was measured using a Look-Locker
      sequence for 2 dose groups (2 mg Fe/kg bw, n = 4, and 5 mg Fe/kg bw, n = 5) and a
      control group (n = 3). RESULTS: A significant increase in R1 was found in
      perfused myocardium after contrast agent injection, in contrast to nonperfused
      myocardium. There was a significantly larger difference in R1 between perfused
      and nonperfused myocardium in the 5 mg Fe/kg bw dose group compared with the
      other 2 groups. The difference in R1 between perfused and nonperfused myocardium
      was significantly higher in vivo than ex vivo. CONCLUSION: A nearly linear R1
      dose response was found in perfused myocardium in vivo. The dose response ex vivo
      was less steep possibly due to larger water exchange limitations.

PMID- 15257210
TI  - Trabecular bone structure of the distal radius, the calcaneus, and the spine:
      which site predicts fracture status of the spine best?
AB  - RATIONALE AND OBJECTIVES: To compare trabecular bone structure measures obtained
      in magnetic resonance images of the distal radius and the calcaneus as well as
      computed tomographic images of the spine versus bone mineral density (BMD) of the
      spine and the calcaneus in the prediction of osteoporotic spine fracture status.
      MATERIAL AND METHODS: High-resolution magnetic resonance images of the calcaneus
      and the distal radius and thin-section computed tomographic images of thoracic
      and lumbar vertebrae were obtained from 74 cadavers. Structure analysis was
      performed using parameters analogous to standard histomorphometry. BMD of the
      spine was determined by using quantitative computed tomography and of the
      calcaneus by using dual x-ray absorptiometry. Spine radiographs of these cadavers
      were assessed concerning vertebral deformities. RESULTS: The diagnostic
      performance in differentiating fracture and nonfracture subjects was highest for
      structure parameters in the spine and slightly lower for these parameters in the
      distal radius and for BMD of the spine. CONCLUSION: In this study structure
      parameters in the spine were best suited to predict the osteoporotic fracture
      status of the spine.

PMID- 15257211
TI  - Magnetic resonance imaging of myocardial perfusion and viability using a blood
      pool contrast agent.
AB  - RATIONALE AND OBJECTIVES: A comprehensive cardiac magnetic resonance (MR)
      examination should comprise imaging of myocardial perfusion, viability, and the
      coronary arteries. Blood pool contrast agents (BPCAs) improve coronary MR
      angiography, whereas their potential for imaging of perfusion and viability is
      unknown. The abilities to noninvasively image myocardial perfusion and viability
      using the BPCA P792 (Guerbet, France) were tested in a closed-chest model of
      nonreperfused myocardial infarction in 5 pigs. MATERIALS AND METHODS: Two to 3
      days after instrumentation, myocardial perfusion imaging with a saturation
      recovery steady-state free precession technique and viability imaging with an
      inversion-recovery fast low-angle shot sequence were conducted on a 1.5-T MR
      scanner using the extracellular contrast agents (ECCA) Gd-DOTA (0.1 mmol Gd/kg)
      and blood pool contrast agent (BPCA) P792 (0.013 mmol Gd/kg). RESULTS: Perfusion
      defects were visualized in all pigs with good correlation between the ECCA and
      the BPCA (1.77 +/- 1.16 cm2 vs. 1.80 +/- 1.19 cm2, r = 0.959, P < 0.01). Reduced
      myocardial perfusion was detected using the ECCA up to 80 seconds after
      injection. In contrast, BPCA administration enabled visualization of perfusion
      defects on equilibrium perfusion imaging in all cases for 10 minutes. The size of
      myocardial infarction detected with viability MR imaging correlated well between
      the standard method (ECCA) and delayed-enhancement imaging with the BPCA (5.40 +/
      3.16 versus 5.52 +/- 3.13 cm3, r = 0.994, P < 0.002). CONCLUSIONS: The BPCA
      investigated in this study allows both reliable detection of perfusion defects on
      first pass and equilibrium perfusion imaging and characterization of viability
      after myocardial infarction. Thus, this contrast agent is suitable for a
      comprehensive cardiac MR examination.

PMID- 15257212
TI  - Gd-BOPTA transport into rat hepatocytes: pharmacokinetic analysis of dynamic
      magnetic resonance images using a hollow-fiber bioreactor.
AB  - RATIONALE AND OBJECTIVES: To investigate the transport of the hepatobiliary
      magnetic resonance (MR) imaging contrast agent Gd-BOPTA into rat hepatocytes.
      MATERIALS AND METHODS: In a MR-compatible hollow-fiber bioreactor containing
      hepatocytes, MR signal intensity was measured over time during the perfusion of
      Gd-BOPTA. For comparison, the perfusion of an extracellular contrast agent (Gd
      DTPA) was also studied. A compartmental pharmacokinetic model was developed to
      describe dynamic signal intensity-time curves. RESULTS: The dynamic signal
      intensity-time curves of the hepatocyte hollow-fiber bioreactor during Gd-BOPTA
      perfusion were adequately fitted by 2 compartmental models. Modeling permitted to
      discriminate between the behaviors of the extracellular contrast agent (Gd-DTPA)
      and the hepatobiliary contrast agent (Gd-BOPTA). It allowed the successfully
      quantification of the parameters involved in such differences. Gd-BOPTA uptake
      was saturable at high substrate concentrations. CONCLUSIONS: The transport of Gd
      BOPTA into rat hepatocytes was successfully described by compartmental analysis
      of the signal intensity recorded over time and supported the hypothesis of a
      transporter-mediated uptake.

PMID- 15257213
TI  - A history of radiation detection instrumentation.
AB  - A review is presented of the history of radiation detection instrumentation.
      Specific radiation detection systems that are discussed include the human senses,
      photography, calorimetry, color dosimetry, ion chambers, electrometers,
      electroscopes, proportional counters, Geiger Mueller counters, scalers and rate
      meters, barium platinocyanide, scintillation counters, semiconductor detectors,
      radiophotoluminescent dosimeters, thermoluminescent dosimeters, optically
      stimulated luminescent dosimeters, direct ion storage, electrets, cloud chambers,
      bubble chambers, and bubble dosimeters. Given the broad scope of this review, the
      coverage is limited to a few key events in the development of a given detection
      system and some relevant operating principles. The occasional anecdote is
      included for interest.

PMID- 15257214
TI  - Extension of NCRP 129 to short-lived radionuclides.
AB  - NCRP 129 contains dose conversion factors for 200 radionuclides that allow one to
      estimate the maximum dose to an individual based on the concentration of the
      radionuclide in the soil and the way in which the land is used. The methodology
      of NCRP 129 has been extended to be applicable to 28 common short-lived
      radionuclides and their progeny, and dose conversion factors were obtained for
      these radionuclides. In addition to applying the NCRP 129 calculational
      methodology to these radionuclides, holdup times from harvest or slaughter until
      consumption have been incorporated into the decay correction equations used to
      determine the maximum annual dose due to the significance of the holdup time with
      respect to the dose from short-lived radionuclides. These holdup times were
      included in the Monte Carlo sampling regimen used in NCRP 129. A test using
      emission rates proportional to those of the Chernobyl event indicated that areas
      of high dose, where rainout occurs, more than doubled in areas where short-lived
      radionuclides from this study were included.

PMID- 15257215
TI  - Contents of cesium, iodine, strontium, thorium, and uranium in selected human
      organs of adult asian population.
AB  - Contents of cesium, iodine, strontium, thorium, and uranium in some selected
      human organs were estimated for adult Asian population using data obtained in
      four Asian countries: China, India, Philippines, and Republic of Korea, as part
      of a Coordinated Research Program of the International Atomic Energy Agency on
      "Ingestion and Organ contents of elements of importance in radiation protection."
      These countries together represent more than 40% of the world population. Highly
      sensitive analytical techniques were employed to measure cesium in skeletal
      muscle, iodine in thyroid, strontium in skeleton, thorium and uranium in
      skeleton, liver, kidneys, and lungs where, in comparison to other organs, these
      elements are present in higher concentrations. The organ contents for adult Asian
      population, when compared with the corresponding data proposed for Reference Man
      by International Commission on Radiological Protection (ICRP), showed about 40
      times lower kidneys content and about 10 times lower skeleton content of uranium.
      The content of thorium in skeleton for Asian population was also half of the ICRP
      Reference Man value. Interestingly, organ contents for the other elements such as
      iodine in thyroid, cesium in skeletal muscle, and strontium in skeleton were
      comparable for Asian and the Caucasian population (represented by ICRP Reference
      Man). Organ contents for these elements were also calculated by applying the new
      ICRP models of these elements to their daily intakes. The comparison of the
      calculated and measured organ contents showed that despite uncertainties in the
      organ content values arising due to the inter-country variations in daily dietary
      intakes, the contents were within a factor of two to three. This observation is
      significant since human data both on organ contents and ingestion were obtained
      at environmental level of intakes. The study suggests that currently available
      ICRP models for these elements are quite realistic.

PMID- 15257216
TI  - Radiostrontium activity concentrations in milk in the republic of Croatia for
      1961-2001 and dose assessment.
AB  - Results of systematic measurements of 90Sr activity concentrations in milk for
      the period 1961-2001 are summarized. An exponential decline of radioactivity
      followed the moratorium on atmospheric nuclear testing. The highest activity of
      90Sr deposited by fallout, 1,060 Bq m(-2), was recorded in 1963, while the peak
      90Sr activity concentration in milk, 1.42 +/- 0.17 Bq L(-1), was recorded in
      1964. The values in year 2001 for fallout deposition and milk were 7.7 Bq m(-2)
      and 0.07 +/- 0.03 Bq L(-1), respectively. The reactor accident at Chernobyl
      caused higher 90Sr levels only in 1986. 90Sr fallout activity affects milk
      activity; the coefficient of correlation between 90Sr fallout activity and 90Sr
      activity concentrations in milk is 0.80. The transfer coefficient from fallout
      deposition to milk was estimated to be 2.5 x 10(-3) Bq y L(-1) per Bq m(-2). The
      dose incurred by milk consumption was estimated for the Croatian population, the
      annual collective effective dose in 2001 being approximately 2.0 person-Sv.

PMID- 15257217
TI  - Radiation quality of a tomotherapy photon fan beam.
AB  - Tomotherapy, a novel radiotherapy technique, uses narrow fan beams for cancer
      patient treatment. Photon energy spectra for a rectangular 10 x 1 cm2 photon beam
      were analyzed in central axis and penumbra regions at depths of 3 to 10 cm in a
      water phantom. A 6 MV beam of a Varian 2100C/D Linear Accelerator was modeled
      using BEAM99 Monte Carlo calculations to simulate energy transport in a water
      phantom. Arrays of 4 x 2 mm2 scoring regions were arranged to cover the central
      axis and penumbra areas. Radiation quality factors were calculated based on dose
      mean linear energy transfer. Although there appears to be a trend towards higher
      quality factor values in the penumbra area, this change is fairly small, at most
      3% in penumbra region. We conclude that change in radiation quality is not likely
      to be an issue in a tomotherapeutic approach when 6 MV x rays are used.

PMID- 15257218
TI  - Guidelines on limits of exposure to ultraviolet radiation of wavelengths between
      180 nm and 400 nm (incoherent optical radiation).

PMID- 15257219
TI  - ICNIRP statement related to the use of security and similar devices utilizing
      electromagnetic fields.

PMID- 15257220
TI  - Medical magnetic resonance (MR) procedures: protection of patients.

PMID- 15257224
TI  - [How to use new treatments for migraine].

PMID- 15257225
TI  - [Current Streptococcus pyogenes sensitivity responsible for acute
      tonsillopharyngitis in France].
AB  - OBJECTIVE: Current guidelines recommend that only tonsillopharyngitis due to
      group A beta-haemolytic streptococcus (GABHS) diagnosed by rapid diagnostic test
      should be treated with antibiotics. Empirical antibiotic therapy must be based on
      epidemiological surveillance of resistance of GABHS to antibiotics. The aim of
      our study was to assess the activity of antimicrobial agents currently
      recommended for the treatment of GABHS tonsillopharyngitis. Method The activity
      of penicillin G, amoxicillin, cefaclor, cefpodoxime, cefuroxime, erythromycin,
      clarithromycin and clindamycin was determined against 93 consecutive GABHS
      isolates collected in 2002. MIC50 and MIC90 of antibiotics tested were determined
      by agar dilution method according to CA-SFM guidelines. Macrolide resistance
      genes (ermA, ermB, mef) were detected by PCR. Genetic diversity of erythromycin
      resistant isolates was analysed by pulsotypic method after digestion by SmaI
      (Finger-printing II, Biorad). RESULTS: The activity of beta-lactam agents tested
      was similar and no resistant strain was detected (0%). Nevertheless, this study
      shows an increasing emergence of erythromycin-resistant GABHS strains reaching
      14% in 2002 (vs. 6.2% in a previous study carried out in 1996-1999). CONCLUSION:
      The empirical antibiotic therapy of tonsillopharyngitis must consider, on the one
      hand, the high risk of GABHS eradication failure associated with in vitro
      resistance to erythromycin and clarithromycin, and on the other hand, the
      sustained susceptibility of GABHS to beta-lactam agents. These results reinforce
      the recommendations to use beta-lactam agents as first line treatment of GABHS
      tonsillopharyngitis.

PMID- 15257226
TI  - [Evolution in the prevalence of intestinal parasitosis in the Fort de France
      University Hospital (Martinique)].
AB  - OBJECTIVE: Determine the prevalence of intestinal parasitosis between January 1,
      1997 and December 31, 1999 in the microbiology laboratory of the Fort de France
      University Hospital. METHOD: Retrospective study of the results of 4684
      parasitological examinations of stools performed in 2704 patients between January
      1, 1997 and December 31, 1999 in this laboratory. RESULTS: This survey showed the
      high prevalence of anguillulosis, found in 51.69% of infested patients and in
      4.56% of the population studied, the ever high prevalence of non or scarcely
      pathogenic amoebas (Endolimax nanus, Dientamoeba fragilis, Entamoeba coli) found
      in 27.19% of infested patients and 1.88% of the population studied, together with
      that of hookworms (12.80% of infested patients and 1.13% of the population), and
      the persistence of lambliasis. This study also revealed the presence of
      cryptosporidies (7 cases) and microsporidies (4 cases) in the patients infected
      by the human immunodeficiency virus. DISCUSSION: These results confirm the trend
      of the past twenty Years and the results of surveys initiated by the national
      statistics board (INSERM) in 1978, 1988 and 1995-1995, with the regression of
      bilharziosis and the persistence of anguillulosis and hookworms. CONCLUSION: The
      improvement in living conditions and hygiene, the combined efforts of the health
      care workers and Authorities in Martinique over the past 30 Years in the fight
      against parasites have led to a great reduction in the prevalence of classical
      intestinal parasitosis. However, new parasites associated with HIV infection have
      appeared.

PMID- 15257227
TI  - [Development of a tool for the identification of socially vulnerable hospital
      patients].
AB  - OBJECTIVE: To develop and assess the metrological properties of a simple to use
      tool to identify socially vulnerable outpatients. METHODS: A multidisciplinary
      group of professionals selected five characteristics identifying social
      vulnerability, integrated in a self-reported questionnaire, from which 5 criteria
      identify the socially vulnerable outpatients consulting the hospital. The
      metrological performance of the tool was assessed on a sample of randomly
      selected outpatients admitted to the emergency department and the results
      referred to the independent assessment of two social workers. The sensitivity and
      specificity of the tool were determined and ROC curves drawn. RESULTS: 222
      patients were included, aged from 15 to 93 Years (mean: 53 Years), 59% of whom
      were men. 78% filled out the questionnaire on their own, while 22% required help,
      usually for physical or material reasons and 87% answered the five questions
      without any difficulty. The kappa coefficient of agreement between the two social
      workers was estimated at 0.94 (CI: 0.89-0.98). The sensitivity of the self
      reported questionnaire was of 70% (CI: 64-76) and its specificity of 77% (CI: 71
      82). The ROC curves showed that the modified tool had a sensitivity of 80% (Sp:
      67%). With only 2 characteristics, this sensitivity was of 76% (Sp: 73%).
      CONCLUSION: This tool, which is based on the advice of various experts, is valid
      and presents acceptable metrological properties. Once some simplifications have
      been made, the questionnaire could be used in routine in any patient consulting
      the hospital because it is acceptable, simple to use and can be rapidly filled
      in.

PMID- 15257228
TI  - [Bilateral pulmonary nodules in an HIV-infected patient].
AB  - INTRODUCTION: Although infectious causes are the most common source of pulmonary
      nodules in HIV-infected patients, malignant diseases such as Kaposi sarcoma and
      lymphoma must also be considered. OBSERVATION: A 40 year-old man, diagnosed with
      HIV infection 16 years earlier and with a satisfactory viro-immunological
      control, was hospitalized for bilateral pulmonary nodules and a dorsal lytic
      mass. Bone and pleural biopsies showed a malignant epithelioid
      hemangioendothelioma. COMMENT: Epithelioid hemangioendothelioma is an uncommon
      low grade vascular tumor. We report the first case in an HIV-infected patient.
      Bilateral pulmonary nodules are common in this malignant disease but are not
      specific. In a HIV-infected patient, such clinical presentation is associated
      with numerous differential diagnoses and must be interpreted in relation to the
      immune status. CONCLUSION: In HIV-patients without immunosuppression, pulmonary
      nodules are often malignant. With the increased survival of these patients, these
      etiologies closer to those of non-infected patients.

PMID- 15257229
TI  - [Gastric necrosis following gastroplasty].
AB  - INTRODUCTION: Over the past ten years, laparoscopic surgery in the treatment of
      morbid obesity has expanded. However, there are few publications describing its
      side effects, notably the occurrence of gastric necrosis. OBSERVATION: Two years
      after laparoscopic-banding for morbid obesity, a case of acute gastroenteritis in
      a 45 Year-old woman proved to be a gastric necrosis. COMMENTS: Relatively
      unknown, this complication is generally revealed by non-specific clinical signs.
      Only emergency oeso-gastro-duodenal opacification permits diagnosis. Early
      diagnosis permits conservative treatment before the onset of necrosis.
      CONCLUSION: Care must be taken when using this technique, which has not yet
      proved its innocuousness, and regular follow-up of the patient is crucial.

PMID- 15257230
TI  - [What progress can be expected in the management of hypertension? Forecast from
      1974 to 2034].
AB  - THE POSITIVE IMPACT OF TREATMENT: Antihypertensive treatments have clearly
      demonstrated their capacity to reduce cardiovascular mortality. The limits to the
      reduction in risk are imputable to insufficient early management, morbidity and
      poor compleance insufficiency of pharmacological treatments, absence of
      individualised adaptation to the causal pathology and inappropriate management of
      other cardiovascular risk factors. TO IMPROVE MANAGEMENT: Rather than creating
      more cardiovascular prevention Centres which only concern specific cases and
      research, it is fundamental to provide physicians, nurses and other health care
      workers with greater competence in hypertension and the management of
      cardiovascular risks. Conceptual changes are also necessary, particularly in that
      which concerns the end of the dichotomy between normotension and hypertension,
      hypercholesterolemia and normocholesterolemia and its individual and populational
      impact. PROMOTION OF NUTRITIONAL MEANS: Nutritional means should not be forgotten
      applied to accompany the whole pharmacological treatment of hypertension, they
      can be used for individual prevention and for reduction of the incidence of high
      blood pressure in the general population. NEW THERAPEUTIC STRATEGIES: Other than
      the search for antihypertensive drugs with greater efficacy and improved
      tolerance, several targets should be envisaged such as optimising the blockage of
      the renin-angiotensin-aldosterone system, inihibiting aldo-synthase. A
      CONSERVATIVE ATTITUDE: Although attractive, the individualisation of treatment
      based on genetic analysis will not be accessible to the majority of hypertensive
      patients. The attitude to be considered in 2004 consists above all in improving
      the use of available drugs at appropriate doses and especially in combinations at
      fixed-doses to allow for an easier therapeutic schedule.

PMID- 15257231
TI  - [Cardiovascular effects of rosiglitazone].
AB  - PROVEN EFFICACY: Since their launch on the French market in 2002,
      thiazolidinediones ("glitazones") prescribing conditions and therapeutic
      indications have progressively widened, although remaining strictly defined by
      the marketing licence. Clinical efficacy on glycemic control (HbA1c and
      glycemia), as well as beneficial metabolic effects (on lipids, insulinresistance
      and beta-cellular function) are now well established. Their side effects,
      generally minor or mild, are also well known. The problem of cardiovascular
      adverse events, although of a low incidence, should be known and recognized,
      notably fluid retention (and oedema) and risk of heart failure, more frequent in
      diabetic than in non diabetic patients. Clinicians must know and take into
      account the particular risk factors, clinical and diagnosis characteristics,
      possible pathophysiological mechanisms and their main preventive measures.
      POTENTIAL BENEFICIAL EFFECTS: On the other hand, numerous experimental and/or
      preliminary data in type 2 diabetic patients, including favourable effects on the
      various pathophysiological mechanisms involved in atherosclerosis and effects on
      cardiovascular risk factors or markers, justifies further large prospective long
      term clinical studies to assess glitazone effects on cardiovascular morbidity and
      mortality in type 2 diabetic patients at high cardiovascular risk. Several
      controlled studies are currently ongoing with rosiglitazone (ADOPT, BARI-2D,
      DREAM, RECORD, etc.), their results within the next coming Years will answer the
      questions on the anticipated benefits of rosiglitazone in terms of cardiovascular
      prevention and/or protection in type 2 diabetic patients.

PMID- 15257232
TI  - [New-generation proton pump inhibitors: progress in the treatment of peptic acid
      diseases?].
AB  - EFFECTS AND INCONVENIENCIES OF THE OLDER PRODUCTS: The proton pump inhibitors
      (PPIs) are now universally considered the treatment of choice for management of
      gastric-acid-related diseases, mainly gastro-oesophageal reflux disease (GERD).
      These drugs share similar properties: general structure, acid-activation step,
      covalent binding to the proton pump of the gastric parietal cell via the
      production of covalent disulphide bonds, relatively stable inhibition of H+,K+
      ATPase. However, the older PPIs (omeprazole, lansoprazole et pantoprazole) have
      notable limitations. These drugs exhibit substantial interpatient variability and
      may have significant interactions with other drugs. These first-generation PPIs
      also do not achieve a rapid and sustained suppression of gastric acid, leading to
      the development of new acid-pump antagonists. The new-generation PPIs,
      esomeprazole and rabeprazole, offer several pharmacokinetic advantages: lower
      oxidative hepatic metabolism rate via the CYP 2C19 reducing the activity
      variations due to genetic polymorphisms and decreasing the risk of significant
      drug-drug interactions (advantages mainly for rabeprazole), lower metabolic
      clearance of esomeprazole (S-enantiomer of omeprazole) increasing plasma
      concentrations and acid suppression of this new PPI, higher accumulation of
      rabeprazole in the parietal cell due to its higher pKa. Gastric pH studies and
      therapeutic trials have demonstrated significant advantages of esomeprazole and
      rabeprazole compared with the older PPIs, which omeprazole is the prototype: a
      greater inhibition of acid secretion, a more rapid onset of action to provide
      reflux symptoms relief over 24 hours with lower GERD-related cost for
      rabeprazole, a sustained acid suppression, cost-effectiveness advantages for
      esomeprazole in the healing and maintenance of erosive esophagitis compared with
      lansoprazole, reduced potential for clinically significant drug-drug interactions
      with rabeprazole compared with omeprazole and esomeprazole. Due to their
      properties, esomeprazole and rabeprazole are the best candidates for "on demand"
      treatment of GERD.

PMID- 15257234
TI  - [Tetanus in a man presenting with a chronic wound].

PMID- 15257233
TI  - [Results of the VALIANT trial in post-myocardial infarction].

PMID- 15257235
TI  - [The management of a genital ulcer 1/2].

PMID- 15257236
TI  - [Measuring the risks. In defense of a more comprehensible public health system].

PMID- 15257237
TI  - [Meningococcal disease due to Neisseria meningitidis serogroup W135 in children.
      Clinical aspects and outcome].
AB  - OBJECTIVE: Meningococcal disease due to Neisseria meningitidis of serogroup W135
      (N. meningitidis W135) is increasing in France. Clinical and outcome data
      concerning these infections in children are scarce. PATIENTS: We report 5 cases
      of children hospitalised in our unit between June 2000 and December 2002 for N.
      meningitidis W135 infection. CASE REPORTS: Among these 5 children aged 19 months
      to 11 years, 3 presented with a primary meningitis and 4 with primary or
      secondary extra-meningeal involvement, articular in 3 cases, pericardial in 2
      cases and ocular in one case. The outcome was favourable without after effects in
      4 cases, marked by a resistant prolonged post-meningococcal inflammatory
      syndrome. COMMENTS: Extra-meningeal septic and/or non septic complications are
      frequent and a prolonged post meningococcal inflammatory syndrome is reported. In
      N. meningitidis W135 infections a careful clinical evaluation of potential extra
      meningeal complications and a long term follow up of children are needed.

PMID- 15257238
TI  - [Lethal osteogenesis imperfecta. Prenatal diagnosis].
AB  - INTRODUCTION: Osteogenesis imparfecta (OI) comprises a group of disorders
      principally affecting type I collagen, which result in increased bone fragility.
      Lethal forms are rare and are characterised by micromelia with malformation of
      the limbs. CASE REPORT: A prenatal diagnosis of lethal OI was made by
      ultrasonography at 18 weeks of gestation and therapeutic abortion was indicated.
      COMMENTS: Molecular biology and genetic studies offer new possibilities of
      prenatal diagnosis, but ultrasonography remains the investigation of choice. It
      confirms the diagnosis by revealing an increase in bone transparency.

PMID- 15257239
TI  - [When insulin creates resistance].

PMID- 15257240
TI  - [Epidemiological data and screening criteria of the metabolic syndrome].
AB  - THREE DEFINITIONS: The metabolic or X syndrome is defined by an association of
      metabolic anomalies leading to an increased risk of cardiovascular complications.
      Today, there are at least 3 definitions of X syndrome: those of WHO, EGIR and
      NCEP. To varying degrees they associate increased abdominal fat, hypertension,
      glucose tolerance abnormality (ranging from hyperinsulinism to diabetes), and
      hypertriglyceridemia with low HDL cholesterol. FROM AN EPIDEMIOLOGICAL POINT OF
      VIEW: The prevalence of metabolic syndrome depends on the definition used and
      varies with the country or ethnic group considered. About 25% of the US and 10%
      of the French adult populations are concerned. THE RISK OF COMPLICATIONS:
      According to clinical trials, people with metabolic syndrome have a 2 to 4-fold
      increase in risk for coronary heart disease. Some of them have a particularly
      high risk (association of most features of the syndrome, association of an
      increased waist circumference and hypertriglyceridemia, presence of biological
      markers such as elevated C-reactive protein or microalbuminuria). Metabolic
      syndrome is also associated with a 4-fold increase in risk for developing
      diabetes.

PMID- 15257241
TI  - [Insulin resistance physiopathology].
AB  - AMONG THE BIOLOGICAL MEDIATORS OF INSULIN RESISTANCE: two compounds released by
      the adipocyte are found, such as free fatty acids and tumor necrosis factor
      alpha. They are incriminated in the deleterious role of visceral adiposity on the
      metabolic parameters. INTRA-CELL CORTISOL: Attention is also focused on the
      potential implication of cortisol in the genesis of metabolic syndrome, because
      cortisol is a potent antagonist of the effect of insulin and its presence in
      excess enhances visceral obesity and insulin resistance. GENETIC ASPECTS:
      Although no major locus has yet been identified, recent findings of several
      mutations or polymorphisms in genes acting in different regulation systems
      (adiponectin, PPARgamma2) also provide an interesting insight into the
      pathogenesis of this syndrome. Moreover, there is growing epidemiological
      evidence that intra-uterine factors could induce a so-called programming of the
      individual that may, at least in part, account for the difficulties encountered
      by the classical genetic approach.

PMID- 15257242
TI  - [Treatment principles for the metabolic syndrome].
AB  - GENERAL PRINCIPLES: The general progression throughout the world in type 2
      diabetes has lead medical Authorities to develop mass screening but also
      prevention measures, notably for "high-risk" subjects such as those exhibiting a
      metabolic syndrome. Studies on the topic have shown that preventing type 2
      diabetes was possible via lifestyle changes, possibly in association with
      pharmacological therapy (metformine, acarbose, thiazolidinediones, orlistat). The
      other therapeutic stakes in the context of the metabolic syndrome also concern
      the management of all identified cardiovascular risk factors. REGARDING
      HYPERTENSION: there are currently no specific recommendations available in the
      framework of metabolic syndrome, with regard to lowering blood pressure and how
      to obtain it. However there is evidence that patients may benefit from the strict
      control of blood pressure (< or =130/85 mm Hg). REGARDING DYSLIPIDEMIA: LDL
      cholesterol remains the main target, with a goal depending on individual
      cardiovascular risk (<1 or 1.30 g/l in the case of metabolic syndrome). Statins
      are of major interest in this context. However, it is also established that
      normalisation of triglycerides and HDL cholesterol contributes to the improvement
      of cardiovascular Issues. The respective indications for fibrates or
      fibrate/statin associations still need to be defined in primary as in secondary
      prevention.

PMID- 15257243
TI  - [Feasibility of administering Tegeline at home. Retrospective study of efficacy,
      safety and tolerance].
AB  - OBJECTIVE: To demonstrate the feasibility of administration Tegeline at home from
      a point of view of efficacy, safety, tolerance, to validate the pertinence of the
      selection and the training of patients who could benefit from this type of
      administration and to assess the long term efficacy and safety. METHOD: This
      retrospective study was conducted in patients exhibiting primary immune
      deficiency and formerly treated with intravenous immunoglobulins at least six
      months in hospital settings, trained by the centre for the training of children
      in the home (Centre de formation au traitement a domicile de l'enfant--CFTDE) and
      having received at least one administration of Tegeline at home from January 1st
      2000. Tegeline contains a mean of 97.6% of whole IgG (58.8% of IgG1, 34.1% of
      IgG2, 5.4% of IgG3 and 1.7% of IgG4). RESULTS: Two hundred and eighteen follow-up
      sheets were completed by 13 patients in whom all the eligibility criteria were
      fulfilled. The total number of infusions per patient ranged from 4 to 41. No
      difficulty in administration was reported in 10 patients, difficulties in placing
      the needle were encountered in 3 other patients and motivating their return to
      the hospital for treatment (after 6 and 10 months) in 2 cases. The infusion flow
      rate was usually of 2 to 3 ml/kg/h. During the follow-up period, no episode of
      infection was noted in 5 patients and 8 presented infections that were treated
      with antibiotics. Regarding safety, the security 'kits' (corticosteroids,
      adrenalin) that were supplied to each patient were never used. Over time, the
      median duration of the infusions at home was of 5 years and 6 months. CONCLUSION:
      In trained and selected patients, this study demonstrated the efficacy, safety
      and tolerance to the administration of Tegeline at home.

PMID- 15257244
TI  - [Management of acute dyspnea].

PMID- 15257246
TI  - Hepatocyte transplantation: state of the art and strategies for overcoming
      existing hurdles.
AB  - Over three decades of research in experimental animals and several clinical
      trials have brought us to the threshold of hepatocyte transplantation for the
      treatment of acute and chronic liver failure, and inherited metabolic disorders.
      However, more extensive clinical studies and routine clinical application are
      hampered by the shortage of good quality of donor cells. To overcome these
      hurdles, current research has focused on the search for alternatives to adult
      primary hepatocytes, such as liver cell progenitors, fetal hepatoblasts,
      embryonic, bone marrow or umbilical cord blood stem cells and conditionally
      immortalized hepatocytes. Cross-species hepatocyte transplantation is also being
      explored. It is hoped that ongoing research will permit the application of
      hepatocyte transplantation to the treatment of a wide array of liver diseases.

PMID- 15257247
TI  - Experimental models for hepatitis C virus (HCV): new opportunities for combating
      hepatitis C.
AB  - Infection with hepatitis C virus (HCV) is a global public health issue. More than
      200 million people in the world are infected with HCV. Hepatitis C is considered
      one of the main causes of chronic hepatitis, cirrhosis, hepatocellular carcinoma
      and liver transplantation. The identification of the viral genome quickly allowed
      delineation of genomic organization, and the structure and biochemical
      characterization of the proteins of HCV. However, it has been difficult to study
      its life cycle, as well as the development of antiviral agents due to the lack of
      a system of permissible culture. Numerous attempts have been reported to
      establish an in vitro system for the study of HCV. Recently, a system of
      efficient culture was established that allows replication of subgenomic molecules
      of HCV in a cell line of human hepatoma. In this revision, after a brief
      description of the molecular biology, means of transmission and clinical
      characteristics of hepatitis C, some of the experimental models are described
      that have been developed to date, focusing mainly on the subgenomic replicon
      system and their use in the development of new antiviral treatments.

PMID- 15257248
TI  - Fatty liver: how frequent is it and why?
AB  - There is increasing evidence that fatty liver may be the most frequent liver
      disorder in Western countries. However, the epidemiology of fatty liver is still
      not fully understood and there is a clear need of better assessing and defining
      the potential role of the risk factors identified by clinical series in the
      general population. This article reviews the available data on the epidemiology
      of fatty liver and addresses some important questions that should be answered in
      much needed future research.

PMID- 15257249
TI  - The relationship of overweight and obesity to high mortality rates from liver
      cirrhosis in Mexico.
AB  - BACKGROUND & AIM: Liver cirrhosis continues to be an important cause of death in
      Mexico. Some data suggest that being overweight is a risk factor for chronic
      liver disease. The aim of this study was to assess the link between the
      incidences of being overweight or obese and mortality from liver cirrhosis in
      Mexico during the period 1990-2001. METHODS: We designed and conducted an
      ecological study of trends with multiple comparisons of regions of Mexico (North,
      Central, Mexico City, and South). We built the time trends according to the
      mortality rates of liver cirrhosis reported by the System of Vital Statistics
      (Health Ministry) in each state for each year from 1990 to 2001. The information
      on prevalences of overweight (body mass index (BMI) = 25-29.9) and obesity (BMI
      >/= 30) was from two national surveys (1993 and 2000). RESULTS: The analysis of
      mortality trends in liver cirrhosis by region showed an increase in the risk of
      death across time. This risk was considerably higher for the South Region (beta =
      1.03, p <0.0001). The mortality rates remained higher than 30 per 100,000
      inhabitants. When we selected the three states with the highest mortality rates
      for each region, the most significant changes in the trends were in the North and
      South regions (beta = 0.75, p <0.0001 and beta = 1.29, p <0.0001, respectively).
      In addition, the prevalence of overweight in the four regions increased from 1993
      to 2000 (percentage change, 10.2-48.2). Obesity was most prevalent in the North
      and South regions in 1993. CONCLUSION: Our observations support the hypothesis
      that obesity might play an important role in the risk of developing liver
      cirrhosis.

PMID- 15257250
TI  - Use of a stiff guidewire in transjugular liver biopsy in patients with a
      pronounced angle of the suprahepatic veins.
AB  - In the performance of a transvascular liver biopsy, the Trucut-type transjugular
      liver biopsy set is advance over a multipurpose catheter place in the
      suprahepatic vein. Occasionally there is a sharp bend between the suprahepatic
      veins and the inferior vein cava and the multipurpose catheter does not provide
      sufficient support to track the biopsy access set. To deal with this problem we
      describe the use of a stiff guidewire for an easy introduction of the biopsy set.

PMID- 15257251
TI  - Gastric varix: radiological-endoscopic correlation.

PMID- 15257252
TI  - Infectious mononucleosis hepatitis: a case-report.
AB  - 46-year-old Mexican-born who lived in Mexico City was admitted to the hospital
      for evaluation with a two-week history of fever, jaundice, and malaise. Physical
      examination he had cardiac murmurs. The liver was palpable 2 cm below the costal
      margins. Liver-function tests showed hypertransaminasemia. The patient had a high
      titer of anti-EBV IgM antibodies, but tests for all other antiviral antibodies
      were negative. The liver biopsy shows EBV latent membrane protein.

PMID- 15257254
TI  - Management of the metabolic syndrome.
AB  - The metabolic syndrome (MetS) is strongly associated with insulin resistance and
      consists of a constellation of factors that raise the risk for cardiovascular
      diseases and diabetes mellitus. Therefore, the primary goals of treating MetS are
      prevention of type 2 diabetes and cardiovascular events. Three levels of
      intervention may be considered for individuals with MetS : 1) management of
      underlying risk conditions by controlling weight excess, enhancing regular
      physical exercise and promoting healthy diet; 2) management of individual risk
      factors such as dyslipidaemia, hypertension, hyperglycaemia and prothrombotic
      state; and 3) targeting insulin resistance by using specific insulin sensitizers
      such as thiazolidinediones. The most important therapeutic intervention effective
      in subjects with MetS should focus on modest weight reduction and regular leisure
      time physical activities. Although lifestyle modification is the first-line
      therapy, drug therapy may be necessary in many patients to achieve recommended
      goals regarding lipid profile, blood pressure and blood glucose control. Rather
      than to use a magic bullet that might fully reverse the underlying cause of the
      syndrome, one appealing alternative would be to use a so-called "polypill"
      targeting each of the components of MetS. However, such a polypill should ideally
      contain numerous molecules that all have shown a potential interest for the
      management of MetS such as metformin, acarbose, a thiazolidinedione, a statin, a
      fibrate, an inhibitor of the renin-angiotensin system, aspirin. The growing
      prevalence and high-risk nature of MetS highlights the need to identify
      individuals with this condition and to treat them with an aggressive
      multitargeted approach.

PMID- 15257255
TI  - Obesity and the metabolic syndrome.
AB  - The metabolic syndrome is a cluster of risk factors for coronary heart disease
      that seemingly have an underlying metabolic causation. Central obesity is the
      centerpiece of the metabolic alterations. Accordingly, increased abdominal
      adiposity contributes to dyslipidemia, hyperglycemia, and hypertension. In about
      20% of the cases with metabolic syndrome, there is also beta-cell dysfunction
      that leads to the clinical manifestation of diabetes mellitus. Recent evidence
      suggests that increased obesity is also associated with inflammation. The role of
      adipose tissue in the causation of metabolic alterations that lead to the
      clinical manifestation of the metabolic syndrome has become a focus of active
      research. Adipose tissue not only secretes non-esterified fatty acids that
      contribute to atherogenic dyslipidemia, steatosis and lipotoxicity. This organ is
      also an active endocrine and paracrine system. It can secrete pro-inflammatory
      factors, pro-insulin resistance factors, and other cytokines and hormones that
      can contribute to hypertension and impaired fibrinolysis. Therefore, the
      metabolic alterations commonly associated with increased central obesity of the
      metabolic syndrome are pro-atherogenic partly because the metabolites are
      proinflammatory.

PMID- 15257256
TI  - Arthropathies and thyroid diseases.
AB  - AIM: Improvement of articular symptoms following thyroidectomy has often been
      observed in patients with an association of thyroid and joint diseases. An
      assessment has therefore been made of the types of arthropathy thus benefited and
      the anatomopathological features of the thyroid in patients with concomitant
      joint diseases. An account is given of the arthropathies associated with nontoxic
      nodular goitre (NTG). METHODS: Three cell markers are examined to identify
      immunocytokine elements differentiating thyroid diseases. RESULTS:
      Immunohistochemical examination shows extravasal lymphocyte infiltrates;
      thyrocytes were negative for HLA-Cl II, CD38 and IL-6R, and only dim-positive for
      HLA-Cl I. Endothelial cells were positive for HLA-Cl I and II and CD38, and
      negative for IL-6R. The lymphocyte were positive for HLA-Cl I, HLA-Cl II and
      CD38, but negative for IL-6R. The follow-up of 6 thyroidectomised patients
      disclosed improvement in joint pain and remission of rheumatoid arthritis and
      spondylarthritis. Association of nodular goitre with arthro-pathies is
      demonstrated. CONCLUSION: Arthritis and arthralgia are frequent in patients with
      thyroid diseases, we particularly found the association with MHNG and Hurthle
      cell adenoma. Arthritis and arthralgia quickly improve after thyroidectomy.
      Immunohistochemical NTG thyrocytes are still normal cells (HLA-Cl II negative) by
      contrast with their HLA-Cl II positivity in autoimmune thyroiditis.

PMID- 15257257
TI  - [Methodological evaluation of an enzyme-immunoassay for plasma Big-et-1
      determination].
AB  - BACKGROUND: The evaluation of big-endothelin (ET)-1 plasmatic concentrations may
      serve as another noninvasive marker in patients with cardiovascular diseases,
      based on the assumption that it may reflect endothelin overproduction more
      accurately than circulating ET-1. For this reason the analytical performance of
      an immunoenzimatic assay for plasma Big-ET-1, with or without a preliminary step
      of extraction, was evaluated. METHODS AND RESULTS: Sensitivity for direct assay
      was 0.15+/-0.010 fmol/ml (n=27), inter-assay variability, evaluated at 2
      different concentrations, resulted 2.5+/-0.062, CV%=5.6 (n=5) and 1.47+/-0.09
      fmol/ml, CV%=12.8 (n=4), respectively, while intra-assay variability was 0.89+/
      0.022 fmol/ml, CV%=5.6. Sensitivity for the assay with extraction resulted 0.71+/
      0.104 (n=6) fmol/ml and intra-assay variability was 3.6+/-0.13 fmol/ml, CV=7.4%
      (n=4). The comparison between the 2 procedures, performed on 107 plasma samples
      at different peptide concentrations, showed a close agreement between the results
      of the 2 procedures for Big-ET-1 values higher than 1 fmol/ml. CONCLUSION: The
      main limitation of the direct assay is due to possible interference effects while
      the correct evaluation of extraction yield of the individual samples is the main
      drawback of the procedure with extraction. These effects become important when
      assaying samples with low levels of analyte. The direct assay of plasma Big-ET-1,
      easier to perform, more rapid and less expensive, could be the choice method.

PMID- 15257258
TI  - [A rare hyperthyroid syndrome].
AB  - The exophthalmos, myxedema, acropachy (EMA) syndrome is a rare extrathyroid
      syndrome, interesting about 1% of the patients affected by extrathyroid
      complications of Graves' disease. The ratio female/male is 3.4:1 and this case
      report is very rare. The patient, a 52-year-old man, presented a serious
      ophthalmopathy with pretibial myxedema, acropachy with joint pain. The triad
      manifested itself after some ophthalmopathy treatments, i.e. total thyroidectomy,
      steroidal retrobulbar therapy and radiotherapy. The patient received T4 therapy
      and the thyroid function status was normal. The appearance of the EMA syndrome
      coincided with the fast worsening of the ophthalmopathy. This case report
      confirms previous observations regarding the chronological sequence of
      presentations of extrathyroidal manifestations of autoimmune thyroid disease. The
      thyroid disease develops first, followed by ophthalmopathy, then dermopathy, and
      finally, acropachy. The thyroid acropachy shows some differences between
      pulmonary and paraneoplastic osteoarthropathy, due to the presence of thyroid
      dermopathy and ophtalmopathy (EMA) and to the different subperiosteal
      proliferation. Steroidal therapy improved the ophthalmopathy, the pretibial
      myxedema and the acropachy. The improvement obtained has been faster as regards
      the exophtalmos and myxedema, slower as regards the acropachy, but of the same
      importance. In conclusion, acropachy is the latest manifestation of EMA and
      coincides with the worsening of ophthalmopathy. The traditional steroidal therapy
      is effective to improve the syndrome.

PMID- 15257259
TI  - Evidence-based surgical treatment of carotid stenosis. Literature review.
AB  - Carotid stenosis is an important cause of transient ischemic attacks and stroke.
      The cause of carotid stenosis is most often atherosclerosis, which accounts for
      10% to 20% of brain infarction cases. Despite the introduction of tissue
      plasminogen activator and other promising experimental therapies for select
      patients with acute ischemic stroke prevention remains the best approach to
      reduce its impact. Stroke-prone patients can be identified and targeted for
      specific interventions. At this juncture, treatment of carotid stenosis is a well
      established therapeutic target and a pillar of stroke prevention. Two main
      strategies exist for the treatment of carotid stenosis. The 1st is stabilization
      or halting the progression of the carotid plaque formation with medications and
      modifications of risk factors (e.g., hypertension, diabetes, smoking, obesity,
      high cholesterol). The 2nd approach is the elimination or reduction of carotid
      stenosis by carotid endarterectomy or angioplasty and stenting. Carotid
      endarterectomy is the mainstay of therapy for symptomatic, severe carotid
      stenosis. Although its role for asymptomatic patients appears more limited, it is
      distinct for severe stenosis. Carotid angioplasty and stenting are techniques in
      maturation with the attractiveness of being less invasive that face the challenge
      of at least replicating the results of surgery. In this article, we will discuss
      the surgical management of symptomatic and asymptomatic carotid stenosis based on
      the evidence provided by the literature.

PMID- 15257260
TI  - Differential diagnosis and treatment of hyponatremia following pituitary surgery.
AB  - Hyponatremia is a frequent occurrence after pituitary surgery, having been
      described in 9% to 35% of the patients. It is produced by the syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH) or, more frequently, by
      the cerebral salt-wasting syndrome (CSWS). The clinical presentation of both
      syndromes is identical and the differential diagnosis can be difficult. The
      determination of the volemic state is essential for the diagnosis, since the
      patients with the SIADH are euvolemic or hypervolemic, while those with CSWS are
      hypovolemic. Several methods can be used to detect the volemic state in these
      patients and, among them, the furosemide test can best discriminate between SIADH
      and CSWS. A furosemide infusion (20 mg) normalizes sodium serum levels in SIADH
      patients, but not in CSWS patients who remain hyponatremic. The differentiation
      between the 2 syndromes is clinically relevant since their treatment is
      antithetical. SIADH patients need liquid restriction of liquids and/or furosemide
      to reduce the volume of extracellular water, while CSWS patients need volume
      replacement with sodium supplementation (or fludrocortisone can be a good
      alternative). The diagnosis and treatment of these syndromes are discussed on the
      basis of the literature reports.

PMID- 15257261
TI  - Routine controls for the geometric accuracy assessment of MR images used in
      neurosurgery.
AB  - AIM: This paper describes the methodology we set up in our hospital to
      investigate whether or not the MR images from our MRI device are geometrically
      reliable for use as reference images in stereotactic neurosurgery procedures. In
      fact, in these clinical procedures geometric accuracy is a prime concern. MRI is
      often the only diagnostic methodology by which the pathology of interest is
      detectable. On the other hand, the physical measurements on which this technology
      lies do non guarantee geometrical accuracy. METHODS: So we set up a measurement
      protocol to assess the geometric accuracy of an MR image. To reach this goal we
      use a self-designed phantom. On this simple phantom, simulating a human head, the
      stereotactic ring used for neurosurgical procedures was mounted. We made
      acquisitions in CT and MRI, and compared the images found. RESULTS: Our findings
      were that, with our MRI device, the geometric accuracy obtained depends only on
      the acquisition matrix used, and is not affected by other technological factors.
      CONCLUSION: The method here described can be used in any site where stereotactic
      neurosurgical procedures are applied on the basis of MR images, as it is simple
      and cheap, both from an economic point of view, and from a machine-time and
      personnel-time point of view.

PMID- 15257262
TI  - The microsurgical approach to extraforaminal lumbar disc herniations. An analysis
      of 15 cases.
AB  - AIM: Extraforaminal lumbar disc herniations are uncommon, but thanks to recent
      progress in imaging procedures, they may be easily diagnosed. Several surgical
      approaches have been described and employed to remove these herniations. The aim
      of this study is to evaluate the clinical, radiological and surgical features
      which differentiate the treatment of this type of hernia from the more common
      surgical approaches to other types of lumbar disc hernias. METHODS: The authors
      report the results of the surgical treatment of 15 cases of extraforaminal lumbar
      disc herniation through an extracanalicular, intertransverse microsurgical
      approach and describe the technique employed. RESULTS: All cases experienced a
      prompt recovery from the preoperative symptoms with no complications, which
      notably reduced the time necessary for postoperative care. No instability was
      documented and none of the cases observed presented the neuropathic pain
      sometimes reported with this method of approach to these herniations. CONCLUSION:
      This particular site of disc herniation can be approached effectively through the
      extracanalicular route. The procedure, however, requires an extremely accurate
      preoperative anatomical evaluation and a good microsurgical experience.

PMID- 15257263
TI  - Microsurgical approach to lumbar synovial cysts. Technical notes.
AB  - Intraspinal extradural synovial cysts are quite common in the lumbar spine. With
      respect to clinical presentation and surgical treatment, juxta-facet cysts
      (ganglion and synovial cysts) share identical characteristics and results.
      Nowadays, current treatment strategies of intraspinal juxta-facet cysts continue
      to inspire controversy regarding appropriate surgical approaches, and include
      many technical options. The purpose of this report is to illustrate the advantage
      of minimally invasive approaches in 3 cases of lumbar synovial cysts. We
      performed a small flavectomy in the 1st case, a transarticular partial facectomy,
      followed by etherologous bone graft fusion in the 2nd case, and a flavectomy and
      partial facectomy in the 3rd case. In our cases, a microsurgical approach to
      lumbar synovial cysts yielded to complete excision of the lesions and excellent
      pain relief, with early mobilization and hospital discharge of the patients. In
      our opinion, minimally invasive approaches and microsurgical excision of lumbar
      juxta-facet cysts are advantageous over conventional lumbar laminectomy because
      they reduce later development of segmental instability at the operative level,
      and therefore a less invasive strategy for intraspinal synovial cysts removal
      should be recommended.

PMID- 15257264
TI  - Malignant prolactinoma: is metastasis a must? Clinico-pathologic and
      immunohistochemical study of a case.
AB  - Pituitary carcinomas are rare tumors which have been conventionally defined as
      primary adenohypophyseal tumors with cerebrospinal or extracranial metastases.
      According to the current criteria even a highly invasive tumor without metastases
      is not considered as malignant. A case of pituitary adenoma is reported with an
      unproven site of metastasis but with rapid increase in prolactin levels (35,000
      ng/ml), showing extensive invasion on radiology, and pathological and
      immunohistochemical studies indicating a highly mitotic variety of tumor. On the
      basis of this case we want to emphasize that extracranial metastasis is not a
      must to label a pituitary adenoma as a malignant tumor. Such aggressive behavior
      of the tumor and clinico-pathological course in itself should be sufficient for
      the tumor to be labeled as malignant.

PMID- 15257265
TI  - Spinal epidural hematoma following coronary thrombolysis. A case report.
AB  - A case of cervicothoracic spontaneous spinal epidural hematoma (SSEH) following
      coronary thrombolysis with r-TPA and intravenous heparin is reported. The
      clinical picture is discussed, as well as the importance of rapid
      neuroradiological diagnosis (with spinal MRI being the method of choice) and
      surgical treatment. Anyway, in these patients, thorough cardiac function
      evaluation and rapid correction of any clotting disorder is necessary prior to
      surgery. With the increasing use of fibrinolytic therapy this complication would
      be more frequent. This underlines the importance of prompt recognition and
      adequate treatment.

PMID- 15257267
TI  - Cranial bone flap fixation with microplates and screws: a new application
      technique. Technical note.
AB  - A new technique of microplates/screws application for bone flap refixation is
      described. The microplates are fitted into a shaped bone groove in such a way
      that the hardware is flush with the edges of the groove thus avoiding definite
      palpable scalp prominence of the skin under hairless portions of the scalp.

PMID- 15257266
TI  - Arnold's neuralgia caused by solitary fibrous tumor. Case report.
AB  - Solitary fibrous tumor (SFT) is a mesenchymal tumor which has been identified in
      a wide variety of localizations, including soft tissues, peritoneum,
      retroperitoneum, mediastinum, upper respiratory tract, nasopharyngeal sinuses,
      periosteum and extremities, orbit, major body cavities, intraspinal and
      intracranial localizations. The authors describe a case of SFT found in the neck
      of a young patient suffering from Arnold's neuralgia. After surgery, diagnosis of
      SFT was based on characteristic histopathological findings, especially on
      immunohistochemical positive staining for CD34 antigen. It has been described
      also the characteristic patterns making this diagnose sure, focusing the point
      that cure is possible with complete excision of the lesion.

PMID- 15257268
TI  - Genetic analysis of a five generation Indian family with BPES: a novel missense
      mutation (p.Y215C).
AB  - PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare
      eye genetic disorder caused by mutations in the FOXL2 gene located at chromosome
      3q23. The purpose of the present study was to carry out genetic analysis of BPES
      in a five-generation Indian family. METHODS: Peripheral blood samples were
      obtained from individuals for genomic DNA isolation. To determine the linkage of
      this family to the FOXL2 locus, haplotype analysis was carried out using
      microsatellite markers from the BPES candidate region. Five overlapping sets of
      primers were used to amplify the entire coding region of the FOXL2 gene for
      mutation detection. Allele-specific oligonucleotide hybridization (ASOH) analysis
      was carried out to determine segregation of the mutation in the family and to
      also determine if the mutation was present in 100 ethnically matched normal
      control chromosomes. RESULTS: Pedigree analysis suggested that BPES segregated in
      this family as an autosomal dominant trait. Cytogenetic analysis in one patient
      did not reveal any rearrangement. Haplotype analysis suggested that this family
      was linked to the FOXL2 locus on chromosome 3q23. DNA sequence analysis showed
      that the BPES phenotype in this family was caused by a novel missense mutation,
      c.881A->G (p.Y215C). CONCLUSIONS: This study reports for the first time a novel
      missense mutation in a five-generation Indian family with BPES. A review of the
      literature showed that the total number of mutations in the FOXL2 gene described
      to date is 42.

PMID- 15257269
TI  - EST analysis of mouse retina and RPE/choroid cDNA libraries.
AB  - PURPOSE: cDNA libraries from the mouse retina have recently been reported, but no
      well characterized library from the retinal pigment epithelium (RPE) or choroid
      of the mouse has yet appeared in the literature. To complement these libraries
      and to provide the first mouse RPE/choroid library, we used freshly dissected
      tissue from adult C57BL/6J mice to construct new retina and RPE/choroid
      libraries. METHODS: Eyes from 100 six to eight week old C57BL/6J mice were
      dissected in groups of 10. The whole retina and RPE/choroid were isolated
      individually and then homogenized before RNA isolation. Over 5000 clones each
      were sequenced from the unamplified and un-normalized retina and RPE/choroid
      libraries. All sequences were analyzed using GRIST (GRouping and Identification
      of Sequence Tags), a bioinformatics program for gene identification and
      clustering. RESULTS: The RPE/choroid library contained 3145 clusters with 76% of
      the clusters representing single clones. Nearly 87% of the clusters corresponded
      to named genes in GenBank, and 8% of the RPE clusters remain unidentified. The
      retina library contained 3190 clusters of which 78% represented only one clone.
      Approximately 85% of the clusters matched sequences in GenBank, and 9% of the
      clusters remain unidentified. The clones most abundant in each library were all
      well-known sequences and both libraries contained a number of tissue specific or
      tissue-enhanced genes. CONCLUSIONS: These new libraries should provide a valuable
      resource for gene discovery and cDNAs for expression analysis and functional
      studies.

PMID- 15257273
TI  - Eating safely during pregnancy.

PMID- 15257274
TI  - Prevention and treatment of postpartum hemorrhage: new advances for low resource
      settings (#2004/042).

PMID- 15257284
TI  - Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in
      tumorigenesis.
AB  - Phosphorylation on certain Ser/Thr-Pro motifs is a major oncogenic mechanism. The
      conformation and function of phosphorylated Ser/Thr-Pro motifs are further
      regulated by the prolyl isomerase Pin1. Pin1 is prevalently overexpressed in
      human cancers and implicated in oncogenesis. However, the role of Pin1 in
      oncogenesis in vivo is not known. We have shown that Pin1 ablation is highly
      effective in preventing oncogenic Neu or Ras from inducing cyclin D1 and breast
      cancer in mice, although it neither affects transgene expression nor mammary
      gland development. Moreover, we have developed an ex vivo assay to uncover that a
      significant fraction of primary mammary epithelial cells from Neu or Ras mice
      display various malignant properties long before they develop tumors in vivo.
      Importantly, these early transformed properties are effectively suppressed by
      Pin1 deletion, which can be fully rescued by overexpression of cyclin D1. Thus,
      Pin1 is essential for tumorigenesis and is an attractive anticancer target. Our
      ex vivo assay can be used to study early events of breast cancer development in
      genetically predisposed mice.

PMID- 15257285
TI  - Conformation-specific binding of p31(comet) antagonizes the function of Mad2 in
      the spindle checkpoint.
AB  - The spindle checkpoint ensures accurate chromosome segregation by delaying
      anaphase in response to misaligned sister chromatids during mitosis. Upon
      checkpoint activation, Mad2 binds directly to Cdc20 and inhibits the anaphase
      promoting complex or cyclosome (APC/C). Cdc20 binding triggers a dramatic
      conformational change of Mad2. Consistent with an earlier report, we show herein
      that depletion of p31(comet) (formerly known as Cmt2) by RNA interference in HeLa
      cells causes a delay in mitotic exit following the removal of nocodazole.
      Purified recombinant p31(comet) protein antagonizes the ability of Mad2 to
      inhibit APC/C(Cdc20) in vitro and in Xenopus egg extracts. Interestingly,
      p31(comet) binds selectively to the Cdc20-bound conformation of Mad2. Binding of
      p31(comet) to Mad2 does not prevent the interaction between Mad2 and Cdc20 in
      vitro. During checkpoint inactivation in HeLa cells, p31(comet) forms a transient
      complex with APC/C(Cdc20)-bound Mad2. Purified p31(comet) enhances the activity
      of APC/C isolated from nocodazole-arrested HeLa cells without disrupting the Mad2
      Cdc20 interaction. Therefore, our results suggest that p31(comet) counteracts the
      function of Mad2 and is required for the silencing of the spindle checkpoint.

PMID- 15257286
TI  - PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate.
AB  - PAM (Protein Associated with Myc) is an almost ubiquitously expressed protein
      that is one of the most potent inhibitors of adenylyl cyclase activity known so
      far. Here we show that PAM is localized at the endoplasmic reticulum in HeLa
      cells and that upon serum treatment PAM is recruited to the plasma membrane,
      causing an inhibition of adenylyl cyclase activity. We purified the serum factor
      that induced PAM translocation and identified it as sphingosine-1-phosphate
      (S1P). Within 15 min after incubation with S1P, PAM appeared at the plasma
      membrane and was detectable for up to 120 min. Sphingosine-1-phosphate induced
      adenylyl cyclase inhibition in two phases: an initial (1-10 min) and a late (20
      240 min) phase. The initial adenylyl cyclase inhibition was Gi-mediated and PAM
      independent. In the late phase, adenylyl cyclase inhibition was PAM dependent and
      attenuated cyclic AMP (cAMP) signaling by various cAMP-elevating signals. This
      makes PAM the longest lasting nontranscriptional regulator of adenylyl cyclase
      activity known to date and presents a novel mechanism for the temporal regulation
      of cAMP signaling.

PMID- 15257287
TI  - Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from
      endothelial cells.
AB  - von-Willebrand factor (vWF) and tissue-type plasminogen activator (tPA) are
      products of endothelial cells acutely released into the vasculature following
      cell activation. Both factors are secreted after intraendothelial Ca2+
      mobilization, but exhibit opposing physiological effects with vWF inducing
      coagulation and tPA triggering fibrinolysis. To identify components that could
      regulate differentially the release of pro- and antithrombogenic factors, we
      analyzed the contribution of Rab3D and the annexin A2/S100A10 complex, proteins
      implicated in exocytotic events in other systems. We show that mutant Rab3D
      proteins interfere with the formation of bona fide Weibel-Palade bodies (WPbs),
      the principal storage granules of multimeric vWF, and consequently the acute,
      histamine-induced release of vWF. In contrast, neither appearance nor exocytosis
      of tPA storage granules is affected. siRNA-mediated downregulation of annexin
      A2/S100A10 and disruption of the complex by microinjection of peptide competitors
      result in a marked reduction in vWF but not tPA secretion, without affecting the
      appearance of WPbs. This indicates that distinct mechanisms underlie the acute
      secretion of vWF and tPA, enabling endothelial cells to fine-regulate the release
      of thrombogenic and fibrinolytic factors.

PMID- 15257288
TI  - Collagenase unwinds triple-helical collagen prior to peptide bond hydrolysis.
AB  - Breakdown of triple-helical interstitial collagens is essential in embryonic
      development, organ morphogenesis and tissue remodelling and repair. Aberrant
      collagenolysis may result in diseases such as arthritis, cancer, atherosclerosis,
      aneurysm and fibrosis. In vertebrates, it is initiated by collagenases belonging
      to the matrix metalloproteinase (MMP) family. The three-dimensional structure of
      a prototypic collagenase, MMP-1, indicates that the substrate-binding site of the
      enzyme is too narrow to accommodate triple-helical collagen. Here we report that
      collagenases bind and locally unwind the triple-helical structure before
      hydrolyzing the peptide bonds. Mutation of the catalytically essential residue
      Glu200 of MMP-1 to Ala resulted in a catalytically inactive enzyme, but in its
      presence noncollagenolytic proteinases digested collagen into typical 3/4 and 1/4
      fragments, indicating that the MMP-1(E200A) mutant unwinds the triple-helical
      collagen. The study also shows that MMP-1 preferentially interacts with the
      alpha2(I) chain of type I collagen and cleaves the three alpha chains in
      succession. Our results throw light on the basic mechanisms that control a wide
      range of biological and pathological processes associated with tissue
      remodelling.

PMID- 15257289
TI  - Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs
      of DNA.
AB  - H2A.Bbd is an unusual histone variant whose sequence is only 48% conserved
      compared to major H2A. The major sequence differences are in the docking domain
      that tethers the H2A-H2B dimer to the (H3-H4)(2) tetramer; in addition, the C
      terminal tail is absent in H2A.Bbd. We assembled nucleosomes in which H2A is
      replaced by H2A.Bbd (Bbd-NCP), and found that Bbd-NCP had a more relaxed
      structure in which only 118+/-2 bp of DNA is protected against digestion with
      micrococcal nuclease. The absence of fluorescence resonance energy transfer
      between the ends of the DNA in Bbd-NCP indicates that the distance between the
      DNA ends is increased significantly. The Bbd docking domain is largely
      responsible for this behavior, as shown by domain-swap experiments. Bbd
      containing nucleosomal arrays repress transcription from a natural promoter, and
      this repression can be alleviated by transcriptional activators Tax and CREB. The
      structural properties of Bbd-NCP described here have important implications for
      the in vivo function of this histone variant and are consistent with its proposed
      role in transcriptionally active chromatin.

PMID- 15257290
TI  - Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1
      in mitosis.
AB  - Geminin is an unstable inhibitor of DNA replication that negatively regulates the
      licensing factor CDT1 and inhibits pre-replicative complex (pre-RC) formation in
      Xenopus egg extracts. Here we describe a novel function of Geminin. We
      demonstrate that human Geminin protects CDT1 from proteasome-mediated degradation
      by inhibiting its ubiquitination. In particular, Geminin ensures basal levels of
      CDT1 during S phase and its accumulation during mitosis. Consistently, inhibition
      of Geminin synthesis during M phase leads to impairment of pre-RC formation and
      DNA replication during the following cell cycle. Moreover, we show that
      inhibition of CDK1 during mitosis, and not Geminin depletion, is sufficient for
      premature formation of pre-RCs, indicating that CDK activity is the major mitotic
      inhibitor of licensing in human cells. Taken together with recent data from our
      laboratory, our results demonstrate that Geminin is both a negative and positive
      regulator of pre-RC formation in human cells, playing a positive role in allowing
      CDT1 accumulation in G2-M, and preventing relicensing of origins in S-G2.

PMID- 15257291
TI  - T4 AsiA blocks DNA recognition by remodeling sigma70 region 4.
AB  - Bacteriophage T4 AsiA is a versatile transcription factor capable of inhibiting
      host gene expression as an 'anti-sigma' factor while simultaneously promoting
      gene-specific expression of T4 middle genes in conjunction with T4 MotA. To
      accomplish this task, AsiA engages conserved region 4 of Eschericia coli sigma70,
      blocking recognition of most host promoters by sequestering the DNA-binding
      surface at the AsiA/sigma70 interface. The three-dimensional structure of an
      AsiA/region 4 complex reveals that the C-terminal alpha helix of region 4 is
      unstructured, while four other helices adopt a completely different conformation
      relative to the canonical structure of unbound region 4. That AsiA induces,
      rather than merely stabilizes, this rearrangement can be realized by comparison
      to the homologous structures of region 4 solved in a variety of contexts,
      including the structure of Thermotoga maritima sigmaA region 4 described herein.
      AsiA simultaneously occupies the surface of region 4 that ordinarily contacts
      core RNA polymerase (RNAP), suggesting that an AsiA-bound sigma70 may also
      undergo conformational changes in the context of the RNAP holoenzyme.

PMID- 15257292
TI  - The carboxy-terminal portion of TnsC activates the Tn7 transposase through a
      specific interaction with TnsA.
AB  - Tn7 transposition requires the assembly of a nucleoprotein complex containing
      four self-encoded proteins, transposon ends, and target DNA. Within this complex,
      TnsC, the molecular switch that regulates transposition, and TnsA, one part of
      the transposase, interact directly. Here, we demonstrate that residues 504-555 of
      TnsC are responsible for TnsA/TnsC interaction. The crystal structure of the
      TnsA/TnsC(504-555) complex, resolved to 1.85 A, illustrates the burial of a large
      hydrophobic patch on the surface of TnsA. One consequence of sequestering this
      patch is a marked increase in the thermal stability of TnsA as shown by
      differential scanning calorimetry. A model based on the complex structure
      suggested that TnsA and a slightly longer version of the cocrystallized TnsC
      fragment (residues 495-555) might cooperate to bind DNA, a prediction confirmed
      using gel mobility shift assays. Donor DNA binding by the TnsA/TnsC(495-555)
      complex is correlated with the activation of the TnsAB transposase, as measured
      by double-stranded DNA cleavage assays, demonstrating the importance of the
      TnsA/TnsC interaction in affecting Tn7 transposition.

PMID- 15257293
TI  - Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.
AB  - Nodals are signaling factors of the transforming growth factor-beta (TGFbeta)
      superfamily with a key role in vertebrate development. They control a variety of
      cell fate decisions required for the establishment of the embryonic body plan. We
      have identified two highly conserved transmembrane proteins, Nicalin and Nomo
      (Nodal modulator, previously known as pM5), as novel antagonists of Nodal
      signaling. Nicalin is distantly related to Nicastrin, a component of the
      Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo.
      Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a
      phenotype that can arise from a defect in mesendoderm patterning mediated by the
      Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an
      increase in anterior axial mesendoderm and the development of an enlarged
      hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was
      rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced
      signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our
      data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during
      mesendodermal patterning in zebrafish.

PMID- 15257294
TI  - Rapid double 8-nm steps by a kinesin mutant.
AB  - The mechanism by which conventional kinesin walks along microtubules is poorly
      understood, but may involve alternate binding to the microtubule and hydrolysis
      of ATP by the two heads. Here we report a single amino-acid change that affects
      stepping by the motor. Under low force or low ATP concentration, the motor moves
      by successive 8-nm steps in single-motor laser-trap assays, indicating that the
      mutation does not alter the basic mechanism of kinesin walking. Remarkably, under
      high force, the mutant motor takes successive 16-nm displacements that can be
      resolved into rapid double 8-nm steps with a short dwell between steps, followed
      by a longer dwell. The alternating short and long dwells under high force
      demonstrate that the motor stepping mechanism is inherently asymmetric, revealing
      an asymmetric phase in the kinesin walking cycle. Our findings support an
      asymmetric two-headed walking model for kinesin, with cooperative interactions
      between the two heads. The sensitivity of the 16-nm displacements to nucleotide
      and load raises the possibility that ADP release is a force-producing event of
      the kinesin cycle.

PMID- 15257295
TI  - Concurrent versus individual binding of HuR and AUF1 to common labile target
      mRNAs.
AB  - RNA-binding proteins HuR and AUF1 bind to many common AU-rich target mRNAs and
      exert opposing influence on target mRNA stability, but the functional
      interactions between HuR and AUF1 have not been systematically studied. Here,
      using common target RNAs encoding p21 and cyclin D1, we provide evidence that HuR
      and AUF1 can bind target transcripts on both distinct, nonoverlapping sites, and
      on common sites in a competitive fashion. In the nucleus, both proteins were
      found together within stable ribonucleoprotein complexes; in the cytoplasm, HuR
      and AUF1 were found to bind to target mRNAs individually, HuR colocalizing with
      the translational apparatus and AUF1 with the exosome. Our results indicate that
      the composition and fate (stability, translation) of HuR- and/or AUF1-containing
      ribonucleoprotein complexes depend on the target mRNA of interest, RNA-binding
      protein abundance, stress condition, and subcellular compartment.

PMID- 15257296
TI  - Cleavage and proteasome-mediated degradation of the basal transcription factor
      TFIIA.
AB  - The transcription factor TFIIA is encoded by two genes, TFIIAalphabeta and
      TFIIAgamma. In higher eukaryotes, the TFIIAalphabeta is translated as a precursor
      and undergoes proteolytic cleavage; the regulation and biological implications of
      the cleavage have remained elusive. We determined by Edman degradation that the
      TFIIAbeta subunit starts at Asp 278. We found that a cleavage recognition site
      (CRS), a string of amino acids QVDG at positions -6 to -3 from Asp 278, is
      essential for cleavage. Mutations in the CRS that prevent cleavage significantly
      prolong the half-life of TFIIA. Consistently, the cleaved TFIIA is a substrate
      for the ubiquitin pathway and proteasome-mediated degradation. We show that
      mutations in the putative phosphorylation sites of TFIIAbeta greatly affect
      degradation of the beta-subunit. We propose that cleavage and subsequent
      degradation fine-tune the amount of TFIIA in the cell and consequently the level
      of transcription.

PMID- 15257297
TI  - Muscleblind proteins regulate alternative splicing.
AB  - Although the muscleblind (MBNL) protein family has been implicated in myotonic
      dystrophy (DM), a specific function for these proteins has not been reported. A
      key feature of the RNA-mediated pathogenesis model for DM is the disrupted
      splicing of specific pre-mRNA targets. Here we demonstrate that MBNL proteins
      regulate alternative splicing of two pre-mRNAs that are misregulated in DM,
      cardiac troponin T (cTNT) and insulin receptor (IR). Alternative cTNT and IR
      exons are also regulated by CELF proteins, which were previously implicated in DM
      pathogenesis. MBNL proteins promote opposite splicing patterns for cTNT and IR
      alternative exons, both of which are antagonized by CELF proteins. CELF- and MBNL
      binding sites are distinct and regulation by MBNL does not require the CELF
      binding site. The results are consistent with a mechanism for DM pathogenesis in
      which expanded repeats cause a loss of MBNL and/or gain of CELF activities,
      leading to misregulation of alternative splicing of specific pre-mRNA targets.

PMID- 15257298
TI  - RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal
      bodies.
AB  - Cajal bodies (CBs) are subnuclear organelles of animal and plant cells. A role of
      CBs in the assembly and maturation of small nuclear ribonucleoproteins (snRNP)
      has been proposed but is poorly understood. Here we have addressed the question
      where U4/U6.U5 tri-snRNP assembly occurs in the nucleus. The U4/U6.U5 tri-snRNP
      is a central unit of the spliceosome and must be re-formed from its components
      after each round of splicing. By combining RNAi and biochemical methods, we
      demonstrate that, after knockdown of the U4/U6-specific hPrp31 (61 K) or the U5
      specific hPrp6 (102 K) protein in HeLa cells, tri-snRNP formation is inhibited
      and stable U5 mono-snRNPs and U4/U6 di-snRNPs containing U4/U6 proteins and the
      U4/U6 recycling factor p110 accumulate. Thus, hPrp31 and hPrp6 form an essential
      connection between the U4/U6 and U5 snRNPs in vivo. Using fluorescence
      microscopy, we show that, in the absence of either hPrp31 or hPrp6, U4/U6 di
      snRNPs as well as p110 accumulate in Cajal bodies. In contrast, U5 snRNPs largely
      remain in nucleoplasmic speckles. Our data support the idea that CBs may play a
      role in tri-snRNP recycling.

PMID- 15257299
TI  - Structural mechanism of the simultaneous binding of two drugs to a multidrug
      binding protein.
AB  - The structural basis of simultaneous binding of two or more different drugs by
      any multidrug-binding protein is unknown and also how this can lead to a
      noncompetitive, uncompetitive or cooperative binding mechanism. Here, we describe
      the crystal structure of the Staphylococcus aureus multidrug-binding
      transcription repressor, QacR, bound simultaneously to ethidium (Et) and
      proflavin (Pf). The structure underscores the plasticity of the multidrug-binding
      pocket and reveals an alternative, Pf-induced binding mode for Et. To monitor the
      simultaneous binding of Pf and Et to QacR, as well as to determine the effects on
      the binding affinity of one drug when the other drug is prebound, a novel
      application of near-ultraviolet circular dichroism (UVCD) was developed. The UVCD
      equilibrium-binding studies revealed identical affinities of Pf for QacR in the
      presence or absence of Et, but significantly diminished affinity of Et for QacR
      when Pf is prebound, findings that are readily explicable by their structures.
      The principles for simultaneous binding of two different drugs discerned here are
      likely employed by the multidrug efflux transporters.

PMID- 15257301
TI  - The effect of phosphoinositide 3-kinase inhibitors on programmed nuclear
      degradation in Tetrahymena and fate of surviving nuclei.

PMID- 15257300
TI  - BLM and the FANC proteins collaborate in a common pathway in response to stalled
      replication forks.
AB  - Fanconi anaemia (FA) and Bloom syndrome (BS) are autosomal recessive diseases
      characterised by chromosome fragility and cancer proneness. Here, we report that
      BLM and the FA pathway are activated in response to both crosslinked DNA and
      replication fork stall. We provide evidence that BLM and FANCD2 colocalise and co
      immunoprecipitate following treatment with either DNA crosslinkers or agents
      inducing replication arrest. We also find that the FA core complex is necessary
      for BLM phosphorylation and assembly in nuclear foci in response to crosslinked
      DNA. Moreover, we show that knock-down of the MRE11 complex, whose function is
      also under the control of the FA core complex, enhances cellular and chromosomal
      sensitivity to DNA interstrand crosslinks in BS cells. These findings suggest the
      existence of a functional link between BLM and the FA pathway and that BLM and
      the MRE11 complex are in two separated branches of a pathway resulting in S-phase
      checkpoint activation, chromosome integrity and cell survival in response to
      crosslinked DNA.

PMID- 15257302
TI  - Apoptosome inactivation rescues proneural and neural cells from
      neurodegeneration.
AB  - Deficiency of the apoptosome component Apaf1 leads to accumulation of
      supernumerary brain cells in mouse embryos. We observed that neural precursor
      cells (NPCs) in Apaf1(-/-) embryos escape programmed cell death, proliferate and
      retain their potential to differentiate. To evaluate the circumstances of Apaf1(
      /-) NPC survival and investigate their fate under neurodegenerative conditions,
      we established cell lines of embryonic origin (ETNA). We found that Apaf1(-/-)
      NPCs resist common apoptotic stimuli and neurodegenerative inducers such as
      amyloid-beta peptide (typical of Alzheimer's disease) and mutant G93A superoxide
      dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results
      were obtained in Apaf1(-/-) primary cells. When death is prevented by Apaf1
      deficiency, cytochrome c is released from mitochondria and rapidly degraded by
      the proteasome, but mitochondria remain intact. Under these conditions, neither
      activation by cleavage of initiator caspases nor release of alternative apoptotic
      inducers from mitochondria takes place. In addition, NPCs can still
      differentiate, as revealed by neurite outgrowth and expression of differentiation
      markers. Our findings imply that the mitochondrion/apoptosome pathway is the main
      route of proneural and neural cells to death and that its inhibition prevents
      them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell
      model is ideally suited for exploring the potential of novel cell therapies for
      the treatment of human neurodegenerations.

PMID- 15257303
TI  - 1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and
      after lithium administration.
AB  - The mechanism of action of lithium is still largely unknown. However, recent
      animal and human studies suggested the possible neuroprotective effects of this
      medication. In particular, a recent magnetic resonance spectroscopy (MRS) study
      showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a
      putative marker of neuronal integrity/functioning, in both bipolar patients and
      normal controls after 4 weeks of lithium administration. We investigated the
      effects of lithium on NAA levels in a sample of healthy individuals using in vivo
      1H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in
      the pathophysiology of bipolar disorder. In vivo short echo-time 1H-MRS
      measurements of 8 cm3 single voxels placed bilaterally in the DLPFC were
      conducted at baseline and after 4 weeks of lithium administration on 12 healthy
      individuals (mean age+/-SD = 25.0+/-9.8 years; six males). After lithium
      administration, no significant differences in NAA, phosphocreatine plus creatine,
      glycerophosphocholine plus phosphocholine (or choline-containing molecules), and
      myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p >
      0.05). Contrary to prior MRS reports in bipolar patients, we found that lithium
      administration did not significantly increase NAA levels in the DLPFC of healthy
      individuals. Future longitudinal studies will be needed to further investigate
      whether chronic lithium treatment increases NAA levels in other brain regions in
      healthy individuals, and whether it promotes changes in these levels in specific
      brain regions in bipolar patients.

PMID- 15257304
TI  - Setting apart the affected: the use of behavioral criteria in animal models of
      post traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) affects about 20-30% of exposed
      individuals. Clinical studies of PTSD generally employ stringent criteria for
      inclusion in study populations, and yet in animal studies the data collection and
      analysis are generally expressed as a function of exposed vs nonexposed
      populations, regardless of individual variation in response. Prior data support
      an approach to animal models analogous to inclusion criteria in clinical studies.
      This series of studies sought to assess prevalence rates of maladaptive vs
      adaptive responses determined according to a more stringent approach to the
      concept of inclusion/exclusion criteria (cutoff behavioral criteria-CBC),
      consisting of two successive behavioral tests (elevated plus maze and acoustic
      startle response tests). The rats were exposed to stressors in two different
      paradigms; exposure to a predator and underwater trauma. The prevalence rates of
      maladaptive responses to stress in these two distinct models dropped over time
      from 90% in the acute phase to 25% enduring/maladaptive response at 7 days, to
      remain constant over 30 days. As setting the affected individuals apart from the
      unaffected approximates clinical studies, it might also help to clarify some of
      the pending issues in PTSD research.

PMID- 15257305
TI  - Caffeine attenuates waking and sleep electroencephalographic markers of sleep
      homeostasis in humans.
AB  - Prolonged wakefulness increases electroencephalogram (EEG) low-frequency activity
      (< 10 Hz) in waking and sleep, and reduces spindle frequency activity
      (approximately 12-16 Hz) in non-rapid-eye-movement (nonREM) sleep. These
      physiologic markers of enhanced sleep propensity reflect a sleep-wake-dependent
      process referred to as sleep homeostasis. We hypothesized that caffeine, an
      adenosine receptor antagonist, reduces the increase of sleep propensity during
      waking. To test this hypothesis, we compared the effects of caffeine and placebo
      on EEG power spectra during and after 40 h of wakefulness. A total of 12 young
      men underwent two periods of sleep deprivation. According to a randomized, double
      blind, crossover design, they received two doses of caffeine (200 mg) or placebo
      after 11 and 23 h of wakefulness. Sleep propensity was estimated at 3-h intervals
      by measuring subjective sleepiness and EEG theta (5-8 Hz) activity, and
      polysomnographic recordings of baseline and recovery nights. Saliva caffeine
      concentration decreased from 15.7 micromol/l 16 h before the recovery night, to
      1.8 micromol/l 1 h before the recovery night. Compared with placebo, caffeine
      reduced sleepiness and theta activity during wakefulness. Compared with sleep
      under baseline conditions, sleep deprivation increased 0.75-8.0 Hz activity and
      reduced spindle frequency activity in nonREM sleep of the recovery nights.
      Although caffeine approached undetectable saliva concentrations before recovery
      sleep, it significantly reduced EEG power in the 0.75-2.0 Hz band and enhanced
      power in the 11.25-20.0 Hz range relative to placebo. These findings suggest that
      caffeine attenuated the build-up of sleep propensity associated with wakefulness,
      and support an important role of adenosine and adenosine receptors in the
      homeostatic regulation of sleep.

PMID- 15257306
TI  - Direct evidence for the involvement of the mesolimbic kappa-opioid system in the
      morphine-induced rewarding effect under an inflammatory pain-like state.
AB  - Recent clinical studies have demonstrated that when morphine is used to control
      pain in cancer patients, psychological dependence is not a major concern. The
      present study was undertaken to ascertain the modulation of psychological
      dependence on morphine under a chronic pain-like state in rats. The prototypical
      mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent
      place preference. In the present study, we found that an inflammatory pain-like
      state following formalin injection significantly suppressed the morphine-induced
      rewarding effect. This effect was almost reversed by s.c. pretreatment with the
      kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg).
      Furthermore, the morphine-induced increase in dopamine (DA) turnover in the
      limbic forebrain was significantly inhibited by treatment with formalin. This
      inhibition was also suppressed by pretreatment with nor-BNI. In addition, in vivo
      microdialysis studies clearly showed that the morphine-induced increase in the
      extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid
      and homovanillic acid, in the nucleus accumbens (N.Acc.) was significantly
      decreased in rats that had been pretreated with formalin. This effect was in turn
      reversed by the microinjection of a specific dynorphin A antibody into the N.Acc.
      These findings suggest that the inflammatory pain-like state induced by formalin
      injection may have caused a sustained activation of the kappa-opioidergic system
      within the N.Acc., resulting in suppression of the morphine-induced rewarding
      effect in rats. The present study provides further evidence of the clinical
      usefulness of morphine in patients suffering from severe pain.

PMID- 15257307
TI  - Mu-opioid receptors are not involved in acute cocaine-induced locomotor activity
      nor in development of cocaine-induced behavioral sensitization in mice.
AB  - Although mu-opioid receptors have been extensively investigated for their role in
      drug reinforcement, little is known about the contribution of these receptors to
      the acute and sensitized locomotor response to cocaine. In this study mu-opioid
      receptor involvement in acute cocaine-induced locomotor activity and in the
      development of cocaine-induced behavioral sensitization was evaluated using mu
      opioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as
      models. In addition, co-administration of the specific mu-opioid receptor
      antagonist CTOP with repeated saline or cocaine injections was used to establish
      the involvement of mu-opioid receptors in sensitization to the locomotor
      stimulant effects of cocaine. The acute locomotor response to cocaine (3, 10, 20,
      or 30 mg/kg i.p.) of mu-opioid receptor knockout or chronic NTX pretreated mice
      was not different from the cocaine response of their respective controls. With
      respect to cocaine-induced behavioral sensitization, induced by daily injections
      of 20 mg/kg cocaine for 11 subsequent days, mu-opioid receptor knockout mice
      developed behavioral sensitization to the locomotor stimulant effects of cocaine
      (challenge 10 mg/kg i.p.) comparable to wild-type littermates and the mu-opioid
      receptor antagonist CTOP did not affect cocaine-induced sensitization either.
      However, mice that were pretreated with NTX exhibited augmented cocaine-induced
      behavioral sensitization relative to placebo pretreated controls, which may be
      ascribed to increased delta-opioid receptor levels as has been described for
      chronic NTX pretreated mice. The present findings suggest that mu-opioid
      receptors are not required for the acute locomotor response to cocaine nor are
      they essential for the development of cocaine-induced behavioral sensitization.

PMID- 15257308
TI  - The nucleus accumbens is not critically involved in mediating the effects of a
      safety signal on behavior.
AB  - Although considerable progress has been made towards understanding the neural
      systems mediating conditioned fear, little is known about the neural mechanisms
      underlying conditioned inhibitors of fear (or safety signals). The present series
      of experiments examined the involvement of the nucleus accumbens (NAC) in
      mediating the effects of safety signals on behavior using a conditioned
      inhibition of fear-potentiated startle paradigm. Neither increasing dopaminergic
      nor decreasing glutamatergic function in the NAC altered the magnitude of
      conditioned fear or conditioned inhibition of fear in rats. Furthermore, large
      pre- or post-training electrolytic lesions of the NAC did not affect acquisition
      or expression of fear-potentiated startle or conditioned inhibition of fear
      potentiated startle. Taken together, these data suggest that the NAC is not
      critically involved in the acquisition or expression of fear-potentiated startle
      or conditioned inhibition of fear-potentiated startle. Previous research has
      implicated the NAC in 'reward-attenuated startle' in which presentation of a
      stimulus paired with food decreased startle responding. The present results,
      therefore, indicate important neural dissociations between the processing of
      appetitive and safety signals, even though behavioral studies and learning
      theories have suggested that these two forms of learning share some
      commonalities.

PMID- 15257309
TI  - Psychostimulants induce low-frequency oscillations in the firing activity of
      dopamine neurons.
AB  - The reinforcing properties of psychostimulants depend critically on their effects
      on dopamine (DA) neurons in the ventral tegmental area (VTA). Using in vivo
      single unit recording in rats and spectral analysis, this study presents evidence
      for a new, non-DA-mediated effect of psychostimulants on VTA DA neurons. Thus, as
      previously observed with D-amphetamine, all psychostimulants tested, including
      cocaine, methamphetamine, and methylphenidate, had two opposing effects on firing
      rate of DA neurons: a DA-mediated inhibition and a non-DA-mediated excitation.
      The latter effect was normally masked by the DA-mediated inhibition and was
      revealed when the inhibition was blocked by a DA antagonist. Using spectral
      analysis, this study further showed that during psychostimulant-induced
      excitation, DA cells exhibited not only an increase in firing rate and bursting
      but also a low-frequency rhythmic oscillation (0.5-1.5 Hz) in their firing
      activity. The oscillatory response was unique to psychostimulants since it was
      not observed with the GABA(A) agonist muscimol, which also increased DA cell
      firing, and not mimicked by the nonpsychostimulant DA agonist L-dopa. Results
      further suggest that the effect requires activation of adrenergic alpha1
      receptors and depends on intact forebrain inputs to DA neurons. Further
      understanding of this novel effect may provide important insights into both the
      mechanism of action of psychostimulants and the neuronal circuitry that controls
      the activity of DA neurons in the brain.

PMID- 15257310
TI  - Retinoblastoma protein function and p16INK4a expression in actinic keratosis,
      squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin
      and links between p16INK4a expression and infiltrative behavior.
AB  - p16INK4a is involved in many important regulatory events in the cell and the
      expression and function is closely associated with the retinoblastoma protein
      (Rb). Earlier, we have in colorectal cancer and in basal cell carcinoma showed
      that p16INK4a is upregulated at the invasive front causing cell cycle arrest in
      infiltrative tumor cells via a functional Rb. This role for p16INK4a as a
      regulator of proliferation when tumor cells infiltrate might besides a general
      cyclin-dependent kinase (cdk) inhibitory effect explain why p16INK4a is
      deregulated in many tumor forms. The expression pattern of p16INK4a in relation
      to Rb-function in squamous cancer and precancerous forms of the skin has not been
      fully detailed. We therefore characterized the expression of p16INK4a, Rb
      phosphorylation and proliferation in actinic keratosis, squamous cell carcinoma
      in situ and invasive squamous cell carcinoma with special reference to
      infiltrative behavior. The expression of p16INK4a varied between the lesions,
      with weak and cytoplasmic p16INK4a expression and functional Rb in actinic
      keratosis. Strong nuclear and cytoplasmic p16INK4a expression was observed in all
      carcinomas in situ in parallel with lack of Rb-phosphorylation but high
      proliferation indicating a nonfunctional Rb. Invasive squamous carcinoma showed a
      mixed p16INK4a expression pattern where some tumors had strong cytoplasmic
      p16INK4a expression, large fraction of Rb-phosphorylated cells and high
      proliferation. Interestingly, despite this disability of p16INK4a to inhibit
      proliferation there was an upregulation of cytoplasmic p16INK4a in infiltrative
      cells compared to tumor cells towards the tumor center. A similar scenario but
      strong and combined nuclear and cytoplasmic p16INK4a expression in infiltrative
      cells, was observed in other invasive squamous cancers. This suggests that the
      p16INK4a upregulation in infiltrative cells is governed independently of the
      subcellular localization or of the potential to affect proliferation via Rb, and
      suggests a potentially proliferation independent function for p16INK4a in
      infiltrative behavior.

PMID- 15257311
TI  - Comparison of human papillomavirus genotypes in high-grade squamous
      intraepithelial lesions and invasive cervical carcinoma: evidence for differences
      in biologic potential of precursor lesions.
AB  - High-grade squamous intraepithelial lesions of the cervix are heterogeneous in
      their invasive potential. Comparison of human papillomavirus types between
      invasive cervical carcinoma and high-grade squamous dysplasia may provide insight
      into this biological variability. Liquid-based Pap specimens from 55 high-grade
      intraepithelial lesions and 47 invasive cervical carcinomas were analyzed by
      reverse line blot for 27 human papillomavirus types designated high,
      intermediate, or low risk. Human papillomavirus DNA was present in all high-grade
      intraepithelial lesions (23 different types) and in 94% (13 types) of invasive
      carcinomas. High-risk types were present in 81% of invasive carcinomas compared
      to 58% of high-grade intraepithelial lesions. Severe dysplasias harbored more
      (79%) high-risk human papillomaviruses as compared to moderate dysplasias (37%).
      In 40% of high-grade dysplasia cases (59% of moderate dysplasias; 21% of severe)
      and 13% of invasive carcinomas, intermediate-risk genotypes were identified in
      the absence of high-risk HPV types. Human papillomavirus 16 was the most common
      type in all categories, including 47% of high-grade squamous dysplasias (26%
      moderate; 68% severe) and 61% of invasive carcinomas. Both high-risk type
      (P=0.0004) and type 16 (P=0.0007) human papillomaviruses were positively
      associated with increasing severity of diagnosis. The heterogeneous nature of
      high-grade squamous dysplasias as compared to invasive carcinoma is evident by
      the wider spectrum of associated human papillomavirus types. Likewise, moderate
      dysplasia appears to be more heterogeneous in viral type than severe dysplasia.
      Moderate cases were more often associated with intermediate-risk types, while
      high-risk types were more prevalent in severe dysplasias and invasive cancers.
      Moderate dysplasia cases harboring viral types infrequently found in cancers may
      have a low risk for progression. Human papillomavirus genotyping of high-grade
      squamous intraepithelial lesions may be important in assessing risk for
      progression to invasion.

PMID- 15257312
TI  - Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative
      disorders.
AB  - A total of 106 trephine biopsy specimens with clinical, laboratory and pathology
      findings corresponding to chronic myeloproliferative disorders (CMPD) were
      analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow.
      Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not
      otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia
      vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome
      (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely
      to moderately diffuse or nodular types in the bone marrow, but the reactive or
      coinciding lymphomatous nature could not be revealed by histology alone in the
      majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene
      rearrangement was successfully performed in 81 out of the 106 DNA specimens
      extracted from formol-paraffin blocks. Out of the 81 samples with good-quality
      DNA, 18 gave a single or double discrete amplification band(s), which was
      reproducible only in four specimens. Sequencing finally proved monoclonal B-cell
      population of both pre- and postfollicular origin in all four samples (5%), one
      CML and three CMPD-NOS. Detailed clinical and pathological investigations
      indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in
      two out of these four patients. We conclude that detailed molecular analysis of
      IgH gene rearrangement in bone marrow samples of CMPD patients is needed to
      identify the true monoclonal B-cell infiltration, which-even without overt
      malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004)
      17, 1521-1530, advance online publication, 16 July 2004;
      doi:10.1038/modpathol.3800225.

PMID- 15257313
TI  - Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue
      arrays in classical Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the
      presence of potentially functional immunoglobulin (Ig) gene rearrangements in the
      neoplastic cells. In contrast to lymphocyte-predominant Hodgkin's lymphoma,
      Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low
      frequency of B-cell marker expression and lack Ig light and Ig heavy messenger
      RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's
      lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or
      BOB.1. By using the tissue microarray technique, we have performed an
      immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's
      lymphoma cases. The results have been correlated with the expression of the B
      cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the
      presence of Epstein-Barr virus and the histological subtype. The percentage of
      CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and
      BSAP were positive in the majority of cases. Considering the positive cases with
      independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1
      and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases,
      the results were similar to those previously described by others. No statistical
      association was found between the transcription factor expression, histological
      subtype and Epstein-Barr virus presence. To our knowledge, this is the largest
      series of classical Hodgkin's lymphoma cases in which the expression of
      transcription factors has been studied. We have found a notorious percentage of
      cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We
      propose that other mechanisms different from the absence of transcription factors
      OCT.2 and BOB.1 might be involved in the control of Ig transcription and B
      lineage in classical Hodgkin's lymphoma.

PMID- 15257314
TI  - Evaluation of p53 mutations in premalignant esophageal lesions and esophageal
      adenocarcinoma using laser capture microdissection.
AB  - p53 mutations have been implicated in the development of esophageal malignancies.
      The purpose of this study was to assess more accurately the incidence and types
      of p53 mutations in Barrett's esophagus (BE) with and without dysplasia and in
      esophageal adenocarcinoma, using pure preparations of epithelial cells obtained
      by laser capture microdissection (LCM). Assays were performed on paraffin
      embedded tissue samples of normal antrum and premalignant and malignant
      esophageal samples from 57 patients, including 16 controls, 10 with BE metaplasia
      alone, 20 with BE-associated dysplasia, and 11 with BE-associated adenocarcinoma.
      All tissues were processed for LCM. DNA was extracted from isolated cells, and
      polymerase chain reaction (PCR) was performed using oligonucleutide primers for
      exons 5-8 of p53. PCR products were processed for DNA sequencing. p53 sequence
      abnormalities were identified in 2/16 cases of normal antrum and
      regenerative/chemical gastritis, 1/10 cases of BE, 1/20 cases of BE with
      dysplasia, and 2/11 cases of adenocarcinomas. The abnormalities occurred in exons
      7 and 8 in the form of point mutations. Our results, using LCM, show that p53
      gene mutations are relatively rare in esophageal preneoplastic and neoplastic
      conditions. Only point mutations were detected, but no deletions/insertions were
      identified.

PMID- 15257315
TI  - Mantle cell lymphomas with clonal immunoglobulin V(H)3-21 gene rearrangements
      exhibit fewer genomic imbalances than mantle cell lymphomas utilizing other
      immunoglobulin V(H) genes.
AB  - A preferential use of one particular immunoglobulin variable heavy chain gene,
      V(H)3-21, has recently been reported in mantle cell lymphoma, where almost all of
      these V(H)3-21+ mantle cell lymphomas showed usage of the same light chain
      Vlambda gene (Vlambda3-19) and also had a tendency towards improved prognosis.
      These findings suggested that V(H)3-21+ mantle cell lymphomas constitute a
      distinct subgroup, possibly with antigen stimulation involved in disease
      pathogenesis. In this study, we applied the comparative genomic hybridization
      (CGH) method on 37 mantle cell lymphoma tumors in order to investigate if the
      V(H)3-21+ tumors are different at the genomic level. Interestingly, V(H)3-21+
      mantle cell lymphomas (n=14) showed significantly fewer genomic aberrations (mean
      2.4) compared to non-V(H)3-21 mantle cell lymphomas (n=23) (mean 4.9). The
      chromosomal aberrations identified in our study were generally in accordance with
      previous CGH studies of mantle cell lymphoma; the most frequent aberration was
      complete or partial loss of chromosome 13, followed by recurrent losses within
      6q, 9p, 9q and 11q and frequent gains in 3q, 7p, 8q and 15q. Deletions within 8p
      and 9p as well as gains in 7p and 15q were found exclusively in the non-V(H)3-21
      utilizing tumors. In summary, V(H)3-21+ mantle cell lymphomas demonstrated both a
      lower number and a different spectrum of genomic aberrations than mantle cell
      lymphoma in general, thus supporting the hypothesis that V(H)3-21+ mantle cell
      lymphomas constitute a new subgroup. The findings presented in this report may
      explain the tendency for a better clinical outcome for patients whose tumors
      utilize V(H)3-21.

PMID- 15257316
TI  - Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite
      instability and APC promoter methylation in the progression of melanocytic
      tumours.
AB  - Adenomatous polyposis coli gene (APC) defects have been demonstrated for the
      first time in familial adenomatous polyposis. Recent reports indicate that the
      APC gene is an intermediary between cell adhesion molecules and the cytoskeleton
      and that it may function as a gatekeeper of colonic epithelial proliferation. The
      objective of this study was to analyse APC's presence in lentigos, primary
      melanomas and melanoma metastases. By immunohistochemistry, APC was demonstrated
      in all lentigos, in 75 out of 88 primary melanomas and in 16 out of 28 melanoma
      lymphatic metastases. The percentage of immunolabelled tumour cells (APC index)
      in lentigos ranged between 5 and 69%, in primary melanomas between 0 and 98% and
      in melanoma metastases between 0 and 52%. Statistically significant differences
      between lentigos and primary melanomas and between lentigos and metastases in APC
      expression were found. In a multivariate analysis, APC showed an independent
      prognostic impact. Analysis of microsatellite instability in the APC locus was
      performed on 29 melanomas. Microsatellite instability was found in 5/29 melanomas
      and loss of heterozygosity in 1/29 melanomas. Promoter methylation of APC was
      found in 6/10 APC-negative primary melanomas and in 9/10 APC-negative melanoma
      lymphatic metastases investigated. We conclude about important role of APC
      alterations for melanoma progression.

PMID- 15257318
TI  - Complementary and Alternative Medicine, When Rigorous, can be Science.

PMID- 15257317
TI  - Downregulation of 14-3-3sigma in ovary, prostate and endometrial carcinomas is
      associated with CpG island methylation.
AB  - The 14-3-3sigma inhibitor of cell cycle progression has been shown to be target
      of epigenetic deregulation in many forms of human cancers; however, its role in
      urological and gynecological cancers has not been studied. Here, we have analyzed
      the expression of 14-3-3sigma, wild-type p53 and mutated p53 in over 300 cases of
      the most common cancers occurring in the urological and gynecological tracts and
      its normal counterpart tissue by immunohistochemistry using the multiple tumor
      tissue microarrays. 14-3-3sigma expression was detected in normal epithelia from
      most organs with sporadic expression in renal tubules and absence in the testis.
      In contrast to normal tissue, 14-3-3sigma expression was lost in 40-60% of
      adenocarcinomas of the breast, ovary, endometrium and prostate. There was no
      association between 14-3-3sigma and wild-type/mutated p53 expression. By
      performing methylation-specific PCR, we showed a close association of 14-3-3sigma
      CpG island methylation and low protein expression levels of 14-3-3sigma. In
      addition, a direct link of 14-3-3sigma mRNA expression levels to CpG island
      methylation is demonstrated in two human cancer cell lines. Loss of 14-3-3sigma
      expression due to promoter hypermethylation may represent the most frequent
      molecular aberration in ovarian, endometrial and prostate adenocarcinomas.

PMID- 15257319
TI  - Toward the Philosophy of CAM: Super-system and Epimedical Sciences.

PMID- 15257320
TI  - Equivalence and Non-inferiority Trials of CAM.

PMID- 15257321
TI  - Evidence-based Reconstruction of Kampo Medicine: Part I-Is Kampo CAM?

PMID- 15257323
TI  - Commentary on CAM and NK Cells by Kazuyoshi Takeda and Ko Okumura.

PMID- 15257322
TI  - CAM and NK Cells.
AB  - It is believed that tumor development, outgrowth and metastasis are under the
      surveillance of the immune system. Although both innate and acquired immune
      systems play roles, innate immunity is the spearhead against tumors. Recent
      studies have revealed the critical role of natural killer (NK) cells in immune
      surveillance and that NK cell activity is considerably influenced by various
      agents, such as environmental factors, stress, foods and drugs. Some of these NK
      cell stimulants have been used in complementary and alternative medicine (CAM)
      since ancient times. Therefore, the value of CAM should be re-evaluated from this
      point of view. In this review, we overview the intimate correlation between NK
      cell functions and CAM agents, and discuss possible underlying mechanisms
      mediating this. In particular, neuro-immune crosstalk and receptors for CAM
      agents are the most important and interesting candidates for such mechanisms.

PMID- 15257324
TI  - Functional Somatic Syndromes: Emerging Biomedical Models and Traditional Chinese
      Medicine.
AB  - The so-called functional somatic syndromes comprise a group of disorders that are
      primarily symptom-based, multisystemic in presentation and probably involve
      alterations in mind-brain-body interactions. The emerging neurobiological models
      of allostasis/allostatic load and of the emotional motor system show striking
      similarities with concepts used by Traditional Chinese Medicine (TCM) to
      understand the functional somatic disorders and their underlying pathogenesis.
      These models incorporate a macroscopic perspective, accounting for the toll of
      acute and chronic traumas, physical and emotional stressors and the complex
      interactions between the mind, brain and body. The convergence of these
      biomedical models with the ancient paradigm of TCM may provide a new insight into
      scientifically verifiable diagnostic and therapeutic approaches for these common
      disorders.

PMID- 15257325
TI  - Neurobiology of Acupuncture: Toward CAM.
AB  - It has long been accepted that acupuncture, puncturing and scraping needles at
      certain points on the body, can have analgesic and anesthetic effects, as well as
      therapeutic effects in the treatment of various diseases. This therapy, including
      acupuncture anesthesia, has drawn the attention of many investigators and become
      a research subject of international interest around the world. Numerous studies
      have demonstrated that the nervous system, neurotransmitters, endogenous
      substances and Jingluo (meridians) may respond to needling stimulation and
      electrical acupuncture. An abundance of information has now accumulated
      concerning the neurobiological mechanisms of acupuncture, in relation to both
      neural pathways and neurotransmitters/hormonal factors that mediate autonomic
      regulation, pain relief and other therapeutics. Early studies demonstrated that
      the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides
      in the periaqueductal gray. Recent evidence shows that nitric oxide plays an
      important role in mediating the cardiovascular responses to EA stimulation
      through the gracile nucleus-thalamic pathway. Other substances, including
      serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate
      and alpha-aminobutyric acid (GABA), are proposed to mediate certain
      cardiovascular and analgesic effects of acupuncture, but at present their role is
      poorly understood. The increased interest in acupuncture health care has led to
      an ever-growing number of investigators pursuing research in the processes of the
      sense of needling touch, transduction of needling stimulation signals,
      stimulation parameters and placebos. In this Review, the evidence and
      understanding of the neurobiological processes of acupuncture research have been
      summarized with an emphasis on recent developments of nitric oxide mediating
      acupuncture signals through the dorsal medulla-thalamic pathways.

PMID- 15257326
TI  - An Alternative Approach to Atopic Dermatitis: Part I-Case-Series Presentation.
AB  - Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A
      substantial portion of AD patients treated with conventional therapy become
      intractable after several cycles of recurrence. Over the last 20 years we have
      developed an alternative approach to treat many of these patients by diet and
      Kampo herbal medicine. However, as our approach is highly individualized and the
      Kampo formulae sometimes complicated, it is not easy to provide evidence to
      establish usefulness of this approach. In this Review, to demonstrate the
      effectiveness of the method of individualized Kampo therapy, results are
      presented for a series of patients who had failed with conventional therapy but
      were treated afterwards in our institution. Based on these data, we contend that
      there exist a definite subgroup of AD patients in whom conventional therapy
      fails, but the 'Diet and Kampo' approach succeeds, to heal. Therefore, this
      approach should be considered seriously as a second-line treatment for AD
      patients. In the Discussion, we review the evidential status of the current
      conventional strategies for AD treatment in general, and then specifically
      discuss the possibility of integrating Kampo regimens into it, taking our case
      series presented here as evidential basis. We emphasize that Kampo therapy for AD
      is more 'art' than technology, for which expertise is an essential pre-requisite.

PMID- 15257329
TI  - Combination Effects of Herbs in a Multi-herbal Formula: Expression of Juzen-taiho
      to's Immuno-modulatory Activity on the Intestinal Immune System.
AB  - Herbal formulas of traditional Japanese (Kampo), Chinese and Korean medicines
      usually comprise multiple herbs in a single formula. These medicines are expected
      to show their clinical effects by chemical, pharmacological and pharmaceutical
      combination effects of multi-herbs. However, little effort has been made so far
      to scientifically clarify the nature of such combination effects. Interestingly,
      for example, though a Kampo medicine Juzen-taiho-to (Shi-Quan-Da-Bu-Tang in
      Chinese) stimulates the immune functions of Peyer's patch cells, none of its
      single component herbs shows such activity. We thus examined the combination
      effect of herbs in the Juzen-taiho-to formula for the expression of its immuno
      stimulating activity. Juzen-taiho-to, a composite formula of 10 herbs, has been
      generally considered to comprise two kinds of basic formula, each of which
      consists of four different herbs in addition to two others. The combinations of
      herbs based on these two basic formulas were evaluated for their stimulating
      activities on cytokine production from murine Peyer's patch cells both in vitro
      and ex vivo. Combined decoction of six among 10 herbs in Juzen-taiho-to is
      crucial for the expression of its stimulating activity on Peyer's patch cells. 3D
      HPLC analysis of the ingredients in the fractions from the combined decoctions
      indicated that, in addition to quantitative changes of ingredients, alterations
      occur in their chemical composition by decoction of different herbs. The
      stimulating activity of Juzen-taiho-to on Peyer's patch cells results from the
      combination effect of its six essential component herbs. This combination effect
      is based on physicochemical interactions among the ingredients of the component
      herbs.

PMID- 15257328
TI  - Traditional and Modern Biomedical Prospecting: Part I-the History: Sustainable
      Exploitation of Biodiversity (Sponges and Invertebrates) in the Adriatic Sea in
      Rovinj (Croatia).
AB  - Nature, especially the marine environment, provides the most effective drugs used
      in human therapy. Among the metazoans, the marine sponges (phylum Porifera),
      which are sessile filter feeders, produce the most potent and highly selective
      bioactive secondary metabolites. These animals (or their associated symbiotic
      microorganisms) synthesize secondary metabolites whose activity and selectivity
      has developed during their long evolutionary history (evochemistry). The
      exploitation of these resources has become possible due to the progress in
      molecular and cell biology. BIOTECmarin, the German Center of Excellence follows
      this rationale. In the past, these animals have been successfully and extensively
      utilized to isolate bioactive compounds and biomaterials for human benefit.
      Pharmaceuticals prepared from marine animals, primarily sponges, have been
      applied since ancient times (Hippocrates, Aristotle and later Plinius). It has
      been reported that extracts and/or components from sponges can be used for the
      treatment of specific diseases. For a systematic and applied-oriented
      exploitation, the successful development of effective compounds largely depends
      on quality of the institutional infrastructure of marine stations and more so on
      the biodiversity. The Center for Marine Research in Rovinj (Croatia) fulfils
      these prerequisites. Founded in 1891, this institute has to its credit major
      discoveries related to exploitation of secondary metabolites/biomaterials from
      sponges for therapeutical application and to obtain biomaterials for general
      wellbeing. This is the first part of a review focusing on biomedical prospecting.
      Here, we have mainly described the historic background. The details of
      techniques, substances, approaches and outlooks will be discussed in the second
      part.

PMID- 15257327
TI  - Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary
      Treatment Strategy.
AB  - Exercise has been widely believed to be a preventive and therapeutic aid in the
      treatment of various pathophysiological conditions such as cardiovascular disease
      and cancer. A common problem associated with such pathologies is cachexia,
      characterized by progressive weight loss and depletion of lean and fat body mass,
      and is linked to poor prognosis. As this syndrome comprises changes in many
      physiological systems, it is tempting to assume that the modulation of the
      psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia
      progression in cancer patients. Cancer cachexia is characterized by a disruption
      in the rhythmic secretion of melatonin, an important time-conditioning effector.
      This hormone, secreted by the pineal gland, transmits circadian and seasonal
      information to all organs and cells of the body, synchronizing the organism with
      the photoperiod. Considering that exercise modulates the immune response through
      at least two different mechanisms-metabolic and neuroendocrine-we propose that
      the adoption of a regular exercise program as a complementary strategy in the
      treatment of cancer patients, with the exercise bouts regularly performed at the
      same time of the day, will ameliorate cachexia symptoms and increase survival and
      quality of life.

PMID- 15257332
TI  - From the National Academies: teaching the science of evolution.

PMID- 15257331
TI  - Approaches to biology teaching and learning: from assays to assessments--on
      collecting evidence in science teaching.

PMID- 15257330
TI  - Ozone Therapy for Tumor Oxygenation: a Pilot Study.
AB  - Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone
      therapy is a non-conventional form of medicine that has been used successfully in
      the treatment of ischemic disorders. This prospective study was designed to
      assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were
      recruited for the study. Systemic ozone therapy was administered by
      autohemotransfusion on three alternate days over one week. Tumor oxygenation
      levels were measured using polarographic needle probes before and after the first
      and the third ozone therapy session. Overall, no statistically significant change
      was observed in the tumor oxygenation in the 18 patients. However, a significant
      decrease was observed in hypoxic values </=10 and </=5 mmHg of pO(2). When
      individually assessed, a significant and inverse non-linear correlation was
      observed between increase in oxygenation and the initial tumor pO(2) values at
      each measuring time-point, thus indicating that the more poorly-oxygenated tumors
      benefited most (rho = -0.725; P = 0.001). Additionally, the effect of ozone
      therapy was found to be lower in patients with higher hemoglobin concentrations
      (rho = -0.531; P < 0.034). Despite being administered over a very short period,
      ozone therapy improved oxygenation in the most hypoxic tumors. Ozone therapy as
      adjuvant in chemo-radiotherapy warrants further research.

PMID- 15257333
TI  - Video views and reviews: mitosis, microfibers, and motility.

PMID- 15257334
TI  - Interdisciplinarity and the undergraduate biology curriculum: finding a balance.

PMID- 15257335
TI  - Intuition and innumeracy.

PMID- 15257336
TI  - New math for biology is the old new math.

PMID- 15257337
TI  - Approaches to cell biology: developing educational multimedia.

PMID- 15257338
TI  - Microscopy images as interactive tools in cell modeling and cell biology
      education.
AB  - The advent of genomics, proteomics, and microarray technology has brought much
      excitement to science, both in teaching and in learning. The public is eager to
      know about the processes of life. In the present context of the explosive growth
      of scientific information, a major challenge of modern cell biology is to
      popularize basic concepts of structures and functions of living cells, to
      introduce people to the scientific method, to stimulate inquiry, and to analyze
      and synthesize concepts and paradigms. In this essay we present our experience in
      mixing science and education in Brazil. For two decades we have developed
      activities for the science education of teachers and undergraduate students,
      using microscopy images generated by our work as cell biologists. We describe
      open-air outreach education activities, games, cell modeling, and other practical
      and innovative activities presented in public squares and favelas. Especially in
      developing countries, science education is important, since it may lead to an
      improvement in quality of life while advancing understanding of traditional
      scientific ideas. We show that teaching and research can be mutually beneficial
      rather than competing pursuits in advancing these goals.

PMID- 15257339
TI  - A hierarchical biology concept framework: a tool for course design.
AB  - A typical undergraduate biology curriculum covers a very large number of concepts
      and details. We describe the development of a Biology Concept Framework (BCF) as
      a possible way to organize this material to enhance teaching and learning. Our
      BCF is hierarchical, places details in context, nests related concepts, and
      articulates concepts that are inherently obvious to experts but often difficult
      for novices to grasp. Our BCF is also cross-referenced, highlighting
      interconnections between concepts. We have found our BCF to be a versatile tool
      for design, evaluation, and revision of course goals and materials. There has
      been a call for creating Biology Concept Inventories, multiple-choice exams that
      test important biology concepts, analogous to those in physics, astronomy, and
      chemistry. We argue that the community of researchers and educators must first
      reach consensus about not only what concepts are important to test, but also how
      the concepts should be organized and how that organization might influence
      teaching and learning. We think that our BCF can serve as a catalyst for
      community-wide discussion on organizing the vast number of concepts in biology,
      as a model for others to formulate their own BCFs and as a contribution toward
      the creation of a comprehensive BCF.

PMID- 15257340
TI  - An approach to improving science knowledge about energy balance and nutrition
      among elementary- and middle-school students.
AB  - Unhealthy diets, lack of fitness, and obesity are serious problems in the United
      States. The Centers for Disease Control, Surgeon General, and Department of
      Health and Human Services are calling for action to address these problems.
      Scientists and educators at Baylor College of Medicine and the National Space
      Biomedical Research Institute teamed to produce an instructional unit, "Food and
      Fitness," and evaluated it with students in grades 3-7 in Houston, Texas. A field
      test group (447 students) completed all unit activities under the guidance of
      their teachers. This group and a comparison group (343 students) completed pre
      and postassessments measuring knowledge of concepts covered in the unit. Outcomes
      indicate that the unit significantly increased students' knowledge and awareness
      of science concepts related to energy in living systems, metabolism, nutrients,
      and diet. Pre-assessment results suggest that most students understand concepts
      related to calories in food, exercise and energy use, and matching food intake to
      energy use. Students' prior knowledge was found to be much lower on topics
      related to healthy portion sizes, foods that supply the most energy, essential
      nutrients, what "diet" actually means, and the relationship between body size and
      basal metabolic rate.

PMID- 15257342
TI  - Pioneers and their legacy in radiology.

PMID- 15257341
TI  - Teaching cell biology to nonscience majors through forensics, or how to design a
      killer course.
AB  - Nonscience majors often do not respond to traditional lecture-only biology
      courses. However, these students still need exposure to basic biological
      concepts. To accomplish this goal, forensic science was paired with compatible
      cell biology subjects. Several topics such as human development and molecular
      biology were found to fulfill this purpose. Another goal was to maximize the
      hands-on experience of the nonscience major students. This objective was
      fulfilled by specific activities such as fingerprinting and DNA typing. One
      particularly effective teaching tool was a mock murder mystery complete with a
      Grand Jury trial. Another objective was to improve students' attitudes toward
      science. This was successful in that students felt more confident in their own
      scientific abilities after taking the course. In pre/post tests, students
      answered four questions about their ability to conduct science. All four
      statements showed a positive shift after the course (p values ranging from.001
      to.036, df = 23; n = 24). The emphasis on experiential pedagogy was also shown to
      increase critical thinking skills. In pre/post testing, students in this course
      significantly increased their performance on critical thinking assessment tests
      from 33.3% correct to 45.3% (p =.008, df = 4; n = 24).

PMID- 15257343
TI  - Military doctors.

PMID- 15257344
TI  - Diagnosis of historical figures.

PMID- 15257346
TI  - The life and work of the Birmingham radiologist Dr James Brailsford (1888-1961).
AB  - James Brailsford went from humble beginnings to become an eminent radiologist
      through his ability, determination and immense diligence. He made a late start in
      medicine but became one of the world's leading authorities on skeletal diseases;
      he wrote the classic textbook The Radiology of Bones and Joints and described the
      eponymous Morquio-Brailsford syndrome. In 1934 he was elected first President of
      the British Association of Radiologists, of which he was founder. This later
      became the Faculty of Radiologists at the Royal College of Surgeons and is now
      the Royal College of Radiologists.

PMID- 15257347
TI  - Andrew Halliday, Kt FRCPE (1781-1839): service in the Napoleonic Wars and West
      Indies, and first physician to the Seamen's Hospital Society.
AB  - Sir Andrew Halliday (1781-1839) was domestic physician to HRH the Duke of
      Clarence (1765-1837) (who was later to become King William IV). He also served in
      the Napoleonic Wars-in Portugal, Spain and Waterloo-as well as in the West
      Indies, and became the first physician to the Seamen's Hospital Society. Unlike
      many of his contemporaries, Halliday was also a prolific author, many of his
      publications being on lunatic asylums in Great Britain and Ireland.

PMID- 15257348
TI  - Grantly Dick-Read, MD (1890-1959).

PMID- 15257349
TI  - Sir William Burnett (1779-1861), professional head of the Royal Naval Medical
      Department and entrepreneur.
AB  - Sir William Burnett (1779-1861) had an active career as a Royal Navy surgeon in
      the French Revolutionary and Napoleonic Wars, including service at the battles of
      St Vincent, the Nile and Trafalgar. From 1822 to 1855 he was professional head of
      the Royal Naval Medical Department, when he provided effective leadership in a
      time of great change. Although his official work earned him the reputation of a
      "hard-working, unimaginative, somewhat harsh man", his correspondence shows a
      very humane centre under the official carapace. His official performance and
      reputation were both eroded towards the end of his career by his determined
      promotion of zinc chloride, for which he held lucrative patents.

PMID- 15257350
TI  - The sooterkin doctor: the London career of John Maubray, MD (1700-1732), "andro
      boethogynist".
AB  - Dr John Maubray (1700-1732) was one of the most prominent man-midwives of
      Georgian London. His emphasis on the importance of physical examination and a
      combination of theoretical and practical teaching seems to have foreshadowed
      later methods of training in midwifery. His espousal of the non-instrumental
      Deventerian system of obstetrics and his activities in the parish of St George's,
      Hanover Square in London, identified him with the dominant Whig party. Although
      he failed to acquire a major patron, his network of social connections enabled
      him to obtain charitable and public service appointments, culminating in his
      chairmanship of the Charitable Corporation.

PMID- 15257351
TI  - William Marsden's Yorkshire family, 1749-1922.
AB  - William Marsden (1796-1867), a Yorkshireman, founded two major London hospitals.
      We know little of his family background, about which his only biography gives a
      highly inaccurate account. It suggests his family were landowners and gentlemen
      farmers. Although their origins were more humble, some at least of his Yorkshire
      relatives prospered-through gardening, banking, manufacturing and even medicine.
      This paper presents information on four generations of Yorkshire Marsdens.

PMID- 15257352
TI  - Sir William Jenner (1815-1898) and Queen Victoria.
AB  - This biographical note outlines the work of Sir William Jenner (1815-1898), court
      physician 1861-93 and President of the Royal College of Physicians 1881-8. He was
      the first to distinguish between typhoid and typhus both clinically and
      pathologically.

PMID- 15257353
TI  - Sir Stuart Threipland (1716-1805), physician-in-chief to Prince Charles Edward
      Stuart during the Jacobite uprising of 1745.
AB  - Stuart Threipland (1716-1805), the son of Sir David Threipland, second baronet of
      Fingask Castle, was an ardent Jacobite. He obtained the Edinburgh MD degree in
      1742, was admitted a fellow of the Edinburgh College of Physicians in 1744 and
      was elected its President in 1766. He accompanied "Bonnie" Prince Charles Edward
      Stuart during the Jacobite uprising of 1745 and went into exile shortly after the
      battle of Culloden in April 1746. He returned to Edinburgh under an Act of
      Indemnity in 1747. While he succeeded to the baronetcy after the death of his
      father in 1746, he was not technically allowed to use this title during his
      lifetime because his father's title and ancestral estates had been confiscated
      after the Battle of Sheriffmuir in 1715. He practised in Edinburgh for the rest
      of his life and outlived all of the other great Jacobite figures involved in the
      1745 uprising.

PMID- 15257354
TI  - Reverend Thomas Havers (1659-1719).

PMID- 15257356
TI  - Xavier Bichat (1771-1802).

PMID- 15257355
TI  - A doctor on the front line: Enrico Pajes (1912-1993).
AB  - We conducted an interview in the summer and autumn of 1991 with Dr Enrico Chaim
      Pajes, a Jewish Polish doctor who trained in Italy before World War II. Pajes was
      arrested when Italy entered the war in 1940. For the next three years he was
      rotated through various prisons. He witnessed the bombing of Campagna in 1943 and
      risked his life to treat the wounded. After the war he started a new life as the
      head of a medical clinic for Jewish displaced persons in Grottaferrata, in the
      suburbs of Rome. How did a Jew of Polish origin end up practising medicine in
      Italy for over 40 years? This oral history is the story of Enrico Pajes's life.

PMID- 15257357
TI  - Why we should contain the "medical-industrial-media complex".

PMID- 15257358
TI  - Evaluation of the rupture of silicone breast implants by mammography,
      ultrasonography and magnetic resonance imaging in asymptomatic patients:
      correlation with surgical findings.
AB  - CONTEXT: Different imaging methods can identify the integrity of breast implants
      and also the extent of possible silicone leakage. Mammography, ultrasonography
      and magnetic resonance imaging are often used to evaluate the integrity of breast
      implants, usually in patients that are symptomatic for rupture. A group of
      clinically asymptomatic patients was taken as a sample. These patients wanted to
      remove or change their breast implants for psychological or cosmetic reasons.
      OBJECTIVE: The purpose of this study was to compare the efficacy of mammography,
      sonography and magnetic resonance imaging in the detection of breast implant
      rupture in an asymptomatic population. TYPE OF STUDY: Prospective study. SETTING:
      Department of Diagnostic Imaging, Universidade de Sao Paulo, Sao Paulo, Brazil.
      METHODS: The participants were 44 asymptomatic patients who subsequently had
      implants surgically removed. Eighty-three implants were evaluated by both film
      screen mammography and high-resolution sonography and 77 implants were evaluated
      by magnetic resonance imaging. The sensitivity and specificity of mammography,
      ultrasonography and magnetic resonance imaging were assessed using predetermined
      diagnostic criteria for implant rupture. All radiological signs were discussed
      and false positives and false negatives were retrospectively evaluated to
      identify the pitfalls in the investigations. RESULTS: The respective sensitivity
      and specificity of mammography were 20% and 89%; sonography, 30% and 81%; and
      magnetic resonance imaging, 64% and 77%. The differences between patients with
      breast implants for cosmetic and oncological reasons were discussed. CONCLUSIONS:
      Our experience suggests that magnetic resonance imaging seems to be the best
      imaging method on its own for the evaluation of rupturing among asymptomatic
      patients.

PMID- 15257359
TI  - Point prevalence of drug prescriptions for elderly and non-elderly inpatients in
      a teaching hospital.
AB  - CONTEXT: Age-related pharmacokinetic and pharmacodynamic changes have been
      extensively documented, and several concurrent diseases may underlie multiple
      drug therapy in the elderly. As a result, the risk of adverse drug reactions and
      drug interactions increases among aged patients. However, only a few studies have
      compared the prescribing patterns for different age groups of hospitalized
      patients or have evaluated the effect of age on drug prescription. OBJECTIVE: To
      compare the prevalence of drug prescriptions for elderly inpatients, with those
      for non-elderly inpatients, in order to assess age-related differences in the
      number of prescribed drugs, drug choices and prescribed doses, and to evaluate
      the prescription appropriateness for the elderly patients. TYPE OF STUDY: Cross
      sectional survey. SETTING: 400-bed tertiary care general teaching hospital.
      PARTICIPANTS: All inpatients on one day of June 1995, except for the Intensive
      Care Unit and for the Departments of Psychiatry, Pediatrics and Obstetrics and
      Gynecology. PROCEDURES: All medicines prescribed to the eligible patients on the
      study day were recorded from the prescription sheets provided by the hospital
      pharmacy. MAIN MEASUREMENTS: Name, therapeutic class, and mean daily dose of the
      prescribed drugs. RESULTS: Of the 273 eligible inpatients, 46.5% were 14-44 years
      old, 33% were 45-64 years old and 20.5% were > 64 years old. Cancer was
      significantly more frequent among the elderly. The mean number of prescribed
      drugs was five for all age groups. The five most prescribed drugs for all
      patients were dipyrone, ranitidine, dipyrone in a fixed-dose combination,
      metoclopramide and cefazolin. The elderly had significantly more prescriptions
      for insulin, furosemide and enoxaparin. For most drugs, the mean prescribed dose
      showed that there was no dose adjustment for elderly patients, and drug choices
      for this age group were sometimes questionable. CONCLUSIONS: There was little
      variation in the prescribing patterns for the elderly when compared with the
      other age strata.

PMID- 15257360
TI  - Mid-arm circumference and mid-arm/head circumference ratio in term newborns.
AB  - CONTEXT: Mid-arm circumference of the newborn is strongly associated with birth
      weight and is a very good indicator of low and insufficient birth weight.
      However, there are few Brazilian studies on the relationship between mid-arm and
      head circumferences and, thus, this does not form part of the routine evaluation
      for newborns. OBJECTIVES: To establish the mid-arm circumference and mid-arm/head
      circumference ratio in a population of term newborns. TYPE OF STUDY: Cross
      sectional study carried out between June 1997 and August 1999. SETTING: Hospital
      Maternidade Leonor Mendes de Barros, Sao Paulo. PARTICIPANTS: Term newborns (66
      males and 65 females) of appropriate growth for gestational age, whose mothers
      were healthy, were included in the study. MAIN MEASUREMENTS: Arm circumference,
      arm circumference/head circumference ratio, birth weight and gestational age were
      measured within 48 hours of birth. Data were considered significant when p <
      0.01. RESULTS: The mean values for the mid-arm circumference were 10.76 cm
      (standard deviation, SD = 0.68) for females and 10.76 (SD = 0.81) for males. The
      mean value for the mid-arm/head circumference ratio was 0.31 (SD = 0.02) for both
      sexes. Mid-arm circumference values were significantly related to birth weight
      and gestational age, whereas mid-arm/head circumference ratio was related only to
      birth weight. CONCLUSIONS: Mid-arm circumference and mid-arm/head circumference
      ratio values were established for the studied population. It was possible to
      obtain curves for both mid-arm circumference and mid-arm/head circumference ratio
      in relation to birth weight. However, for mid-arm circumference, it was only
      possible to obtain curves in relation to gestational age. The use of the
      regression curves did not seem powerful enough to predict the mid-arm
      circumference and mid-arm/head circumference ratio in this population of term
      newborns. There were no gender differences for either of the measurements
      studied.

PMID- 15257361
TI  - Praying correlates with higher quality of life: results from a survey on
      complementary/alternative medicine use among a group of Brazilian cancer
      patients.
AB  - CONTEXT: The use of complementary/alternative medicine has been little studied in
      Brazil. OBJECTIVE: The purpose of this study was to determine the prevalence of
      complementary/alternative medicine use among a group of Brazilian cancer patients
      and correlate these findings with the patients' quality of life. TYPE OF STUDY:
      Descriptive. SETTING: Oncology Institute of the Faculdade de Medicina do ABC,
      Santo Andre, Sao Paulo, Brazil. PARTICIPANTS: 100 cancer patients. PROCEDURES:
      The EORTC QLQ C-30 quality of life questionnaire was applied together with
      another questionnaire on the use of complementary/alternative medicine. MAIN
      MEASUREMENTS: Use of complementary/alternative medicine and quality of life.
      RESULTS: 89% of the patients had already used complementary/alternative medicine,
      63% were currently using it and most of them (77.7%) believed in the efficacy of
      complementary/alternative medicine for their treatment. The type most used was
      individual prayer (77.5%). We found a significant association between believing
      in the efficacy of complementary/alternative medicine and praying (individually
      or in groups), in comparison with better scores on the functional (p = 0.001) and
      overall health (p = 0.001) quality of life scales. Multivariate analysis
      confirmed these findings regarding praying and also showed that believing in
      complementary/alternative medicine correlated significantly with functional and
      symptom quality of life scores. CONCLUSION: The prevalence of
      complementary/alternative medicine use in this group of cancer patients was high.
      Praying and belief in the efficacy of complementary/alternative medicine
      correlated significantly with an overall better quality of life, and therefore
      these practices should not be discouraged by physicians. New prospective studies
      should be conducted in order to better characterize the efficacy of such
      alternative therapeutic approaches.

PMID- 15257362
TI  - Verrucous carcinoma of the bladder with koilocytosis unassociated with vesical
      schistosomiasis.
AB  - CONTEXT: Verrucous carcinoma of the bladder is a very rare malignant neoplasm,
      histologically similar to condyloma acuminatum. Usually it shows association with
      vesical schistosomiasis (bilharziasis). Only 13 cases unrelated to bilharziasis
      have been reported to date, and none of them reported koilocytosis, a typical
      finding in human papillomavirus infection. CASE REPORT: We report a case of
      verrucous carcinoma of the bladder that was unrelated to bilharziasis, with
      koilocytosis and absence of human papillomavirus. The literature relating to the
      topic is discussed.

PMID- 15257363
TI  - Lingual thyroid causing dysphonia: evaluation and management. Case report.
AB  - CONTEXT: Lingual thyroid gland is a rare clinical entity that is caused by the
      failure of the thyroid gland to descend to a normal cervical location during
      embryogenesis. The occurrence of an ectopic thyroid gland located at the base of
      the tongue may cause problems for the patient, with symptoms of dysphagia,
      dysphonia, upper airway obstruction or even hemorrhage at any time from infancy
      through adulthood. CASE REPORT: We report on a case of lingual thyroid gland in a
      41-year-old female patient. The embryology and diagnosis of ectopic thyroid are
      discussed and its management is outlined. Features of the diagnostic and
      therapeutic evaluation are described with attention to the clinical findings,
      laboratory tests, thyroid scan and computed tomography imaging studies employed
      in the confirmation of diagnosis and planning of appropriate treatment. The
      history of the condition is reviewed and a treatment strategy is outlined.
      Surgical excision of the gland is reserved for cases of gland enlargement that
      result in compromised airways (dysphagia or dysphonia) or recurrent hemorrhage.

PMID- 15257364
TI  - DNA typing from vaginal smear slides in suspected rape cases.
AB  - In an investigation of suspected rape, proof of sexual assault with penetration
      is required. In view of this, detailed descriptions of the genitalia, the thighs
      and pubic region are made within the forensic medical service. In addition,
      vaginal swabs are taken from the rape victim and some of the biological material
      collected is then transferred to glass slides. In this report, we describe two
      rape cases solved using DNA typing from cells recovered from vaginal smear
      slides. In 1999, two young women informed the Rio de Janeiro Police Department
      that they had been victims of sexual assaults. A suspect was arrested and the
      victims identified him as the offender. The suspect maintained that he was
      innocent. In order to elucidate these crimes, vaginal smear slides were sent to
      the DNA Diagnostic Laboratory for DNA analysis three months after the crimes, as
      unique forensic evidence. To get enough epithelial and sperm cells to perform DNA
      analysis, we used protocols modified from the previously standard protocols used
      for DNA extraction from biological material fixed on glass slides. The quantity
      of cells was sufficient to perform human DNA typing using nine short tandem
      repeat (STR) loci. It was 3.3 billion times more probable that it was the
      examined suspect who had left sperm cells in the victims, rather than any other
      individual in the population of Rio de Janeiro.

PMID- 15257366
TI  - [Dilated cardiomyopathy in children--is there an ecocardiographic prognostic
      index?].

PMID- 15257365
TI  - Efficacy of a triple therapy for Helicobacter pylori eradication in a well
      developed urban area in Brazil.
AB  - CONTEXT: Helicobacter pylori eradication has become the standard treatment for
      peptic ulcer disease. Triple therapy with omeprazole plus two antibiotics has
      been used. Due to the lack of ideal treatment and the high rates of primary
      resistance to nitroimidazoles, the use of clarithromycin has been adopted.
      OBJECTIVE: To determine the Helicobacter pylori eradication rates using
      lansoprazole, amoxicillin and clarithromycin for seven days, in patients with
      peptic ulcer disease in a well developed urban area in Brazil. METHODS: This was
      a retrospective, open-label study carried out at the School of Medicine of the
      Fundacao ABC. It included 130 patients with peptic ulcer disease (upper
      endoscopy) who had been tested positive for Helicobacter pylori infection (urease
      test, histology or breath test), without previous treatment. Patients were
      treated with lansoprazole 30 mg, amoxicillin 1,000 mg and clarithromycin 500 mg
      b.i.d., for seven days. Eradication was verified after 90 days. RESULTS: Follow
      up data were available for 94 patients. Their mean age was 52.23 years; 51.54%
      were woman, 84.31% white, 37.69% smokers, 20.77% using nonsteroidal anti
      inflammatory drugs and 8.46% alcoholics. Upper endoscopy revealed that 78.46% had
      duodenal ulcers and 21.53% had gastric ulcers (a 4:1 DU:GU ratio). The
      eradication rates were 85.11% per protocol and 61.54% by intention to treat; 97%
      had no adverse effects. CONCLUSION: Triple therapy using lansoprazole,
      amoxicillin and clarithromycin is well tolerated with high eradication rates and
      forms a good alternative for developing countries.

PMID- 15257367
TI  - [The cardiologist should suspect more thyroid dysfunction!].

PMID- 15257368
TI  - How can the echocardiogram be useful for predicting death in children with
      idiopathic dilated cardiomyopathy?
AB  - OBJECTIVE: To determine the echocardiographic predicting factors of death in
      children with idiopathic dilated cardiomyopathy. METHODS: A retrospective study
      of 148 children with idiopathic dilated cardiomyopathy diagnosed between
      September 1979 and March 2003 was carried out. The inclusion criteria were as
      follows: heart failure and a reduction in contractility on the echocardiogram in
      the absence of congenital or secondary heart disease. Four hundred and seventy
      examinations during a period of 244.8 months of evolution were analyzed. The
      following parameters were assessed: left atrial dimension (LAD); left
      atrium/aorta ratio (LAD/Ao); left ventricular systolic (LVSD) and diastolic
      (LVDD) dimensions; left ventricular mass (LVmass); right ventricular dimension
      (RVD); left ventricular ejection fraction (LVEF); left ventricular shortening
      fraction (% SH); severity of the insufficiency of the atrioventricular and
      pulmonary valves; and right ventricular systolic (RVSP) and diastolic (RVDP)
      pressures. The significance level adopted was alpha < 0.05. RESULTS: The mean age
      was 2.37 years, and 35 patients died (23.7%--95 CI = 17.1% to 31.2%). The
      analysis of variance showed the following: LAD (p<0.0001); LAD/Ao (p<0.0001);
      LVSD (p=0.0061); LVDD (p=0.0086); LVmass (p<0.0001); LVEF (p=0.0074); %SH
      (p=0.0072); and RVD (p<0.0001). Worsening of mitral (MI) (p=0.0113) and tricuspid
      (TI) insufficiencies (p=0.0044) were markers of death, and the presence of MI,
      TI, and moderate/severe pulmonary insufficiency were deleterious to survival. The
      Cox proportional hazards regression model showed the following independent
      predictors of death: LAD/Ao (p=0.0487); LVEF (<0.0001); and the presence of
      moderate/severe MI (p=0.0419). CONCLUSION: Patients with a progressive increase
      in LAD/Ao, a reduction in LVEF, and progressive worsening of MI, regardless of
      the clinical treatment, should be considered for early heart transplantation.

PMID- 15257369
TI  - Contrast echocardiography in the diagnosis of intrapulmonary vascular dilations
      in candidates for liver transplantation.
AB  - OBJECTIVE: To determine the importance of contrast echocardiography in the
      diagnosis of intrapulmonary vascular dilations in patients with severe liver
      disease, who are candidates for liver transplantation. METHODS: The study
      comprised 76 patients with chronic liver disease and no evidence of intrinsic
      pulmonary disease, heart failure, or congenital heart disease with intracardiac
      communications, who underwent transthoracic echocardiography with second harmonic
      imaging. Thirty-two of them underwent consecutive transesophageal study. The
      result of contrast echocardiography was considered positive when the presence of
      contrast was detected in the left cardiac chambers with a delay of 4 to 6 cardiac
      cycles after initial opacification of the right cardiac chambers. RESULTS: The
      prevalence of intrapulmonary vascular dilations was 53.9% (41/76 patients). The
      sensitivity, specificity, positive and negative predictive values, and accuracy
      of transthoracic echocardiography as compared with those of transesophageal
      echocardiography for confirming pulmonary vascular abnormalities in patients with
      liver disease were, respectively, 75%, 100%, 100%, 80%, and 87.5%. The degree of
      arterial oxygenation showed no correlation with the occurrence of a positive
      echocardiographic study. Arterial hypoxemia (PaO2 < 70 mm Hg) was observed in 9
      (15.9%) of the 76 patients. The echocardiographic study was positive in 37
      (55.2%) of the 67 nonhypoxemic patients and in 4 (44.4%) of the 9 hypoxemic ones.
      CONCLUSION: Contrast echocardiography proved to be effective, easy, and safe to
      use in candidates for liver transplantation. Transthoracic echocardiography may
      be used in the diagnostic routine of intrapulmonary vascular dilations, the
      transesophageal study being reserved for inconclusive cases with clinical
      suspicion.

PMID- 15257370
TI  - Thyroid dysfunction and cardiological management in patients receiving
      amiodarone.
AB  - OBJECTIVE: To determine the prevalence of thyroid dysfunction in patients
      receiving amiodarone, and the possible associated factors. The study also aimed
      at assessing the effect of amiodarone on thyroid function through the application
      of a questionnaire to cardiologists. METHOD: Fifty-six patients chronically (> 3
      months) receiving amiodarone were assessed by measurement of their serum levels
      of TSH, free T4, total T3, and anti-TPO antibodies. Patients with changes in TSH
      levels were defined as having thyroid dysfunction (TD). RESULTS: The prevalence
      of thyroid dysfunction was 33.9%. No difference was observed between this group
      and that of patients with no dysfunction, except for the greater prevalence of
      anti-TPO positivity in patients with TD (P=0.02). Subclinical hypothyroidism was
      diagnosed in 10 (17.9%) patients and clinical hypothyroidism in 6 (10.7%). The
      prevalence of subclinical hyperthyroidism was 3.6% and that of clinical
      hyperthyroidism was 1.8%. Anti-TPO antibodies were positive in 5 (8%) patients
      (of whom, 4 had thyroid dysfunction). When compared with patients negative for
      anti-TPO antibodies, that group had a greater prevalence of dysfunction (80% vs
      29.4%; P=0.04). Only 49.2% of the cardiologists routinely treated their patients'
      thyroid function, and the prevalence of the referred dysfunction for most of them
      ranged from 1 to 10%. CONCLUSION: The prevalence of thyroid dysfunction in our
      population was high, showing the need for implementing a laboratory routine. The
      cardiologists disagreed greatly in regard to the type of follow-up required for
      patients using amiodarone.

PMID- 15257372
TI  - Strategy for identifying an efficient dosage of beta-blocker for elderly patients
      with myocardial ischemia and preserved left ventricular function.
AB  - OBJECTIVE: To assess the strategy of titration for prescribing an efficient
      dosage of propranolol to reduce myocardial ischemia in the elderly. METHODS: The
      study comprised 14 elderly men (73.6 +/- 5.3 years) with stable coronary heart
      disease documented on coronary cineangiography, ischemic response to exercise
      testing, and preserved left ventricular function. Titration was performed to
      identify the dosage of propranolol that would cause a 15% reduction in heart rate
      at the end of a 50 W load (corresponding to normal daily activities in the
      elderly) in weekly exercise tests. Synchronous scintigraphic study of the cardiac
      chambers was performed at rest and during exercise prior to and after propranolol
      use. RESULTS: The reductions in heart rate with the 50 W load and at rest were
      similar (21% vs 20%; P=0.5100). Propranolol improved the duration of exercise
      (12.2 +/- 2.0 min vs 13.1 +/- 1.8 min; P=0.0313) and abolished the changes in the
      ST segment induced by exercise in 8 (57%) patients. At rest, the ejection
      fraction was not modified by the beta-blocker. During maximum exercise,
      propranolol reduced the end-systolic volume index and increased ejection
      fraction. CONCLUSION: The strategy of using beta-blockers to reduce heart rate by
      15% with a 50 W load is safe and beneficial in the elderly patient with
      myocardial ischemia and preserved ventricular function. The dose of beta-blocker
      used reduced myocardial ischemia and improved tolerance to exercise without
      hampering ventricular performance during maximum exercise.

PMID- 15257371
TI  - Cardiovascular diseases in the elderly: analysis of the behavior of mortality in
      a municipality in the Southern Region of Brazil from 1979 to 1998.
AB  - OBJECTIVE: To know the behavior of mortality due to cardiovascular diseases in
      the elderly living in the municipality of Maringa, in the Brazilian state of
      Parana. METHODS: The causes of death over 20 years were studied according to sex,
      age, and groupings of the International Classification of Diseases, 9th and 10th
      Revisions, using the mortality database of the Ministry of Health. RESULTS: In
      regard to total deaths in the elderly, the proportional mortality due to
      cerebrovascular disease and ischemic heart disease decreased 42.5% and 34.4%,
      respectively, while that due to hypertension increased 119%, increasing from 2.1%
      to 4.6%. A 51.2%, 44.6%, and 12.5% decrease occurred, respectively, in the risk
      of death due to cerebrovascular disease, ischemic heart disease, and other forms
      of heart disease. For cerebrovascular disease and ischemic heart disease, the
      decrease in the estimate of the risk of death was greater among women, while for
      the other forms of heart disease, the decrease was greater among men. In regard
      to age groups, the risk of death increases as age advances for each
      cardiovascular disease in both sexes. CONCLUSION: Cardiovascular diseases
      continue to play an important role in morbidity and mortality in the elderly
      population, requiring even greater effort from health care providers for their
      prevention and treatment.

PMID- 15257373
TI  - Severe volume depletion leading to mitral insufficiency.
AB  - We report a patient with profound hypovolemia who developed dynamic left
      ventricular outflow tract obstruction and severe mitral regurgitation. Both the
      outflow tract obstruction and mitral regurgitation resolved with volume
      replacement. Unlike previous reports of dynamic left ventricular outflow
      obstruction and mitral regurgitation, the degree of mitral regurgitation was
      severe. Possible mechanisms are discussed.

PMID- 15257374
TI  - [Case 2/2004--fever, chest pain, dyspnea and edema in a 42-year-old man].

PMID- 15257375
TI  - [Case 6/2004--A 14-month-old infant with Fallot tetralogy and with a discreet
      pulmonary hyperflow].

PMID- 15257376
TI  - [Isaacs' syndrome. Diagnosis and differential diagnosis of neuromyotonia].
AB  - Neuromyotonia is a clinical and electrophysiological syndrome of spontaneous
      muscle fiber activity due to hyperexcitability of peripheral nerve origin causing
      generalised, visible myokymia and muscular cramps. Electromyography shows
      abnormal doublet and triplet discharges of high intraburst frequency as well as
      myokymic and neuromyotonic discharges. Fasciculations and fibrillation potentials
      are common. Most commonly, neuromyotonia is an acquired immune-mediated disorder
      (Isaacs' syndrome) showing elevated antibody levels against presynaptic, voltage
      gated, potassium channels. Some of these patients have additional autonomic
      (hyperhidrosis) and/or CNS symptoms similar to those from limbic encephalitis
      (referred to then as Morvan's syndrome). We report on a patient with Isaacs'
      syndrome and discuss the clinical and electrophysiological features,
      pathophysiology, diagnosis, and differential diagnosis of diseases with
      peripheral nerve hyperexcitability.

PMID- 15257378
TI  - [Clinical courses of acute and chronic neuroborreliosis following treatment with
      ceftriaxone].
AB  - Between 1990 and 2000, a total of 101 patients with acute (n=86) or chronic
      (n=15) neuroborreliosis (proven by clinical data, pleocytosis in the CSF, and
      elevated Borrelia burgdorferi-specific antibody indices) were treated with 2 g of
      ceftriaxone per day for either 2 or 3 weeks. The patients were reexamined
      clinically and serologically after 3, 6, and 12 months. Six (12) months after the
      antibiotic treatment, about 93% (95%) of the patients with acute neuroborreliosis
      and 20% (66%) of the patients with chronic neuroborreliosis were cured. One year
      after treatment, four patients with acute neuroborreliosis still suffered from
      facial palsy and five with chronic neuroborreliosis still had moderate spastic
      ataxic gait disturbance. The prognosis of facial palsy in neuroborreliosis is
      quite similar to that in idiopathic facial palsy, while that in chronic
      neuroborreliosis largely depends on the time elapsed before diagnosis.

PMID- 15257379
TI  - [Doctor reports of a neurological clinic in the view of permanent resident
      neurologists and nerve doctors].
AB  - Eight discharge reports involving five diagnoses (anterior territory ischemic
      stroke, epilepsy, Parkinson's syndrome, multiple sclerosis, polyneuropathy) from
      five neurological departments were peer-reviewed by five neurologists working in
      out-patient (private) practice. The review considered the diagnosis, case
      history, clinical status, laboratory investigation, differential diagnosis and
      treatment. Criticism mainly involved the quality of the clinical assessment, lack
      of clinical status at discharge, narrow or incomplete differential diagnosis and
      the quality of the neurophysiological investigations for epilepsy and
      polyneuropathy. Improvement potential was seen for the speed of reporting, better
      comprehensibility, omission of irrelevant information, greater participation of
      experienced neurologists in report writing, and standardization.

PMID- 15257377
TI  - [Multiple sclerosis: potential therapeutic options and update of ongoing
      studies].
AB  - The therapeutic options for the treatment of multiple sclerosis (MS) have
      experienced enormous progress over recent years. Despite these encouraging
      developments, available therapies are only partially effective, and the ultimate
      goal of curing MS is still far from being attained. The improved understanding of
      the cellular and molecular mechanisms of MS (immune) pathogenesis together with
      recent shifts in paradigms led to a variety of new therapeutic targets and
      approaches. In addition to modulation of the inflammatory process, therapeutic
      approaches focussing on active neuroprotection, remyelinization, and regeneration
      have become increasingly important. Based on current concepts of the MS
      pathogenesis, this article summarizes new therapeutic approaches. Substances and
      strategies currently tested in clinical trials are reviewed.

PMID- 15257380
TI  - [Multimodal computed tomography in acute cerebral infarction. Experience with a
      standardized protocol in 100 patients].
AB  - Computed tomography (CT) is the standard method of brain imaging in acute stroke.
      To an experienced examiner, nonenhanced CT will exclude hemorrhage and may
      indicate early ischemic signs. Reliable description of an ischemic area and the
      underlying vascular disease is not possible in the acute phase but is possible,
      particularly within the first hours, when therapeutic decisions on matters such
      as systemic thrombolysis are to be made. For such rapid decision-making, imaging
      must provide more information. Novel, contrast-enhanced CT techniques can provide
      this information. Perfusion CT (CTP) can show brain perfusion, allowing one to
      distinguish between reversible and irreversible damage in an ischemic area. Also,
      CT angiography (CTA) can detect occlusion or stenosis in the relevant
      vasculature. Using a modern, multislice CT scanner, it is now possible to combine
      these modalities of imaging. In a fast protocol for emergency evaluation, all
      three methods can be performed and evaluated to provide the crucial information
      within 15 min. In the first 102 patients examined within 6 h of symptom onset
      using this protocol, multimodal CT contributed substantially to therapeutic
      decisions, even though there are some limitations in these methods.

PMID- 15257381
TI  - [Superficial siderosis of the CNS. 2 cases and a review of the literature].
AB  - Superficial siderosis of the CNS is a rare disease. The superficial deposition of
      haemosiderin in the cerebrum, cerebellum and spinal cord is due to chronic and
      recurrent subarachnoidal haemorrhage (SAH). Known sources of bleeding are
      vascular CNS-tumours, CSF-cavity lesions, vascular malformations, nerve root
      lesions and neurosurgical interventions. Detection of the source of bleeding is
      successful in only about 50% of cases. The clinical syndrome is characterized by
      sensorineural deafness, cerebellar ataxia and pyramidal signs. CSF-investigation
      might be indicative for SAH, while ferritin and ionic iron can be elevated in the
      CSF. CT is unspecific and insensitive but MR imaging of the brain and spinal cord
      is very sensitive and specific. The elimination of the source of bleeding alone
      might prevent the progression of the disease, therefore, an early and extensive
      search for this source is highly recommended.

PMID- 15257382
TI  - [Autoimmune functional disorders of the thyroid during interferon-beta-1b
      treatment in patients with multiple sclerosis. Case report and literature
      review].
AB  - Occurrence of thyroid autoimmunity and dysfunction following interferon alpha
      treatment of viral hepatitis and other diseases are known adverse effects and
      have been ascribed to the cytokine's general immunomodulatory and -activating
      properties. However, in spite of its extensive application, there have been few
      reports of such incidents during interferon beta (IFN-beta-1a/b) therapy, which
      is considered the standard treatment of relapsing-remitting multiple sclerosis
      (MS), and prospective studies have been published only recently. Here we present
      the case of a 38-year-old woman with Graves' disease including massive thyroid
      associated ophthalmopathy appearing de novo following IFN-beta-1b therapy for MS.
      A literature search revealed an 11% (5% clinically overt) overall incidence of de
      novo thyroid dysfunction in IFN-beta-treated MS patients, mostly autoimmune
      hyperthyroidism. (Large-scale comparative studies for IFN-beta-1a are not
      available at present). Specific treatment but not necessarily discontinuation of
      IFN-beta-1b therapy was required in most cases. Female gender, pre-existing
      thyroid autoimmunity, and family history of thyroid disorders are presumable risk
      factors for thyroid dysfunction de novo during IFN-beta-1b treatment.

PMID- 15257383
TI  - [Cerebrotendinous xanthomatosis--a treatable metabolic disorder].

PMID- 15257384
TI  - Tetrahedral homonuclear organoelement clusters and subhalides of aluminium,
      gallium and indium.
AB  - This review is focused on the synthesis and the reactivity of tetrahedral
      organoelement clusters of the heavier elements of third main-group aluminium,
      gallium, and indium, which have been known for about a decade. They possess the
      elements in an unusually low oxidation state of +1 and have direct element-
      element interactions between their four constituents. Each cluster atom is
      further attached to one terminal and in most cases a bulky organic substituent,
      which prevents disproportionation by steric shielding. The synthesis of these
      compounds succeeds by different methods such as the reduction of suitable
      organoelement(III) halides with alkali metals and magnesium or the treatment of
      element(I) halides with lithium organyls. They are deeply coloured, and their
      bonding situation may best be described by delocalized molecular orbitals. They
      show a singular chemical reactivity, which results in the formation of many
      secondary products possessing unprecedented structures and properties. The
      synthesis of organoelement subhalides still containing the elements in low
      oxidation states is discussed in more detail in the second part of this review.
      These compounds are easily accessible by the careful oxidation of the clusters
      with halogen donors such as hexachloroethane or with AlX(3)/X(2) mixtures. They
      produce dimers via halogen bridges, but in certain cases monomers were observed
      even for the solid state. They are very effective starting compounds for
      secondary reactions and the generation of new products containing the elements in
      unusual oxidation states by salt-elimination reactions, for instance.

PMID- 15257385
TI  - Epicuticular wax of large and small white butterflies, Pieris brassicae and P.
      rapae crucivora: qualitative and quantitative comparison between diapause and non
      diapause pupae.
AB  - We compared the quantity and quality of the epicuticular wax of diapause and non
      diapause pupae in two closely related Pieris species, P. brassicae and P. rapae
      crucivora. Main components of their epicuticular wax were identified as
      hydrocarbons. In P. brassicae, more than 95% of hydrocarbons were saturated
      regardless of whether the pupae were in diapause or not. In P. rapae crucivora,
      93% of hydrocarbons were saturated in non-diapause pupae whereas in diapause
      pupae 41% were saturated and 59% unsaturated. From measurements of body surface
      area by nuclear magnetic resonance microimaging, we calculated the average
      thickness of the wax layer. The thickness in diapause and non-diapause pupae of
      P. brassicae was 800 and 160 nm, respectively. In P. rapae crucivora, the
      thickness was 195 nm in diapause and 11 nm in non-diapause. This is the first
      report to clarify the compositional difference in epicuticular wax between
      diapause and non-diapause pupae.

PMID- 15257386
TI  - Coordinated gene expression for pheromone biosynthesis in the pine engraver
      beetle, Ips pini (Coleoptera: Scolytidae).
AB  - In several pine bark beetle species, phloem feeding induces aggregation pheromone
      production to coordinate a mass attack on the host tree. Male pine engraver
      beetles, Ips pini (Say) (Coleoptera: Scolytidae), produce the monoterpenoid
      pheromone component ipsdienol de novo via the mevalonate pathway in the anterior
      midgut upon feeding. To understand how pheromone production is regulated in this
      tissue, we used quantitative real-time PCR to examine feeding-induced changes in
      gene expression of seven mevalonate pathway genes: acetoacetyl-coenzyme A
      thiolase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3
      methylglutaryl coenzyme A reductase, mevalonate 5-diphosphate decarboxylase,
      isopentenyl-diphosphate isomerase, geranyl-diphosphate synthase (GPPS), and
      farnesyl-diphosphate synthase (FPPS). In males, expression of all these genes
      significantly increased upon feeding. In females, the expression of the early
      mevalonate pathway genes (up to and including the isomerase) increased
      significantly, but the expression of the later genes (GPPS and FPPS) was
      unaffected or decreased upon feeding. Thus, feeding coordinately regulates
      expression of the mevalonate pathway genes necessary for pheromone biosynthesis
      in male, but not female, midguts. Furthermore, basal mRNA levels were 5- to 41
      fold more abundant in male midguts compared to female midguts. This is the first
      report of coordinated regulation of mevalonate pathway genes in an invertebrate
      model consistent with their sex-specific role in de novo pheromone biosynthesis.

PMID- 15257387
TI  - Floral CO(2) emission may indicate food abundance to nectar-feeding moths.
AB  - As part of a study of the roles of the sensory subsystem devoted to CO(2) in the
      nectar-feeding moth Manduca sexta, we investigated CO(2) release and nectar
      secretion by flowers of Datura wrightii, a preferred hostplant of Manduca. Datura
      flowers open at dusk and wilt by the following noon. During the first hours after
      dusk, when Manduca feeds, the flowers produce considerable amounts of nectar and
      emit levels of CO(2) that should be detectable by moths nearby. By midnight,
      however, both nectar secretion and CO(2) release decrease significantly. Because
      nectar production requires high metabolic activity, high floral CO(2) emission
      may indicate food abundance to the moths. We suggest that hovering moths could
      use the florally emitted CO(2) to help them assess the nectar content before
      attempting to feed in order to improve their foraging efficiency.

PMID- 15257388
TI  - Clocks for sex: loss of circadian rhythms in ants after mating?
AB  - This paper describes experiments on the locomotor activity rhythm of queens of
      the ant species Camponotus compressus, which were performed to investigate the
      consequences of mating on circadian clocks. Locomotor activity rhythm of virgin
      and mated queens was monitored individually under constant conditions of the
      laboratory. The locomotor activity rhythm of virgin queens entrained to a 24 h
      (12:12 h) laboratory light/dark (LD) cycle and free-ran under constant dim red
      light (RR) with a free-running period ( tau) of approximately 24 h. The locomotor
      activity of the mated queens on the other hand was arrhythmic during the period
      when they were laying eggs, and robust rhythmicity appeared soon after the egg
      laying phase was over. The tau of the locomotor activity rhythm of mated queens
      was significantly greater than that of virgin queens. These results are contrary
      to the commonly held belief that the role of circadian clocks in ant queens
      ceases after mating flights, thus suggesting that circadian clocks of ant queens
      are adaptively plastic and display activity patterns, perhaps depending on their
      physiological state and tasks in the colony.

PMID- 15257389
TI  - Does exaggerated morphology preclude plasticity to cuckoldry in the midshipman
      fish ( Porichthys notatus)?
AB  - In species with more than one male reproductive morph, there typically exists a
      larger morph with exaggerated secondary sexual characters, and a smaller morph
      with reduced secondary sexual characters. These "exaggerated" and "reduced"
      morphologies are commonly thought to represent specializations to alternative
      behavioral reproductive tactics-large body size and exaggerated secondary sexual
      characters should both facilitate territoriality, courtship, and pair-spawning;
      while small body size and reduced secondary sexual characters should facilitate
      "sneaky" cuckoldry. Given this postulated relationship between morphology and
      behavior, we examined the relationship between the morphology of exaggerated
      males and cuckoldry. In a field and aquarium study of the midshipman fish, a fish
      with both exaggerated and reduced morphs, we demonstrated cuckoldry in some males
      of the exaggerated morph. Since the "reduced" morphology is thought to be an
      adaptation towards sneaky cuckoldry, we predicted that, of males with the
      exaggerated morph, less-exaggerated (smaller) males would be better able to gain
      proximity to the spawning pair during cuckoldry. In contrast to that prediction,
      access to the spawning pair during cuckoldry increased with the body size of the
      cuckolding exaggerated-morph males. This may be related to our observation that
      exaggerated males often cuckolded aggressively. Thus the "exaggerated" morphology
      need not preclude adaptive plasticity to cuckoldry, and may even aid it.

PMID- 15257390
TI  - Factors inducing the intense burrowing activity of the red-swamp crayfish,
      Procambarus clarkii, an invasive species.
AB  - The burrowing activity of the invasive red-swamp crayfish, Procambarus clarkii,
      was studied along a 25-m-long transect in an irrigation ditch system in Italy.
      Our objective was to understand the factors inducing this species' intense
      digging, which can result in bank collapse and consequently in severe damage to
      both agricultural fields and natural ecosystems. Burrow morphology and position,
      together with their occupancy by crayfish and digging, were recorded once every 6
      h for 10 consecutive days. The majority of burrows were simple, although a few
      had a chimney and were constructed at a farther distance from the water surface
      than simple burrows. Burrow occupancy and digging, together with their
      plugged/unplugged status, were constant throughout a 24-h cycle and were not
      related to any abiotic parameter of the habitat. Crayfish occupied and dug a
      burrow for a relatively short time (6 h on average). Once abandoned, old burrows
      were rarely reoccupied and often collapsed, while crayfish excavated new ones. As
      a result, the overall number of burrows increased. This massive use of banks by
      P. clarkii seems to be related to soil composition and humidity, which favour
      crayfish digging but also cause the easy collapse of burrows.

PMID- 15257392
TI  - Honeybee combs: construction through a liquid equilibrium process?
AB  - Geometrical investigations of honeycombs and speculations on how honeybees
      measure and construct the hexagons and rhombi of their cells are centuries old.
      Here we show that honeybees neither have to measure nor construct the highly
      regular structures of a honeycomb, and that the observed pattern of combs can be
      parsimoniously explained by wax flowing in liquid equilibrium. The structure of
      the combs of honeybees results from wax as a thermoplastic building medium, which
      softens and hardens as a result of increasing and decreasing temperatures. It
      flows among an array of transient, close-packed cylinders which are actually the
      self-heated honeybees themselves. The three apparent rhomboids forming the base
      of each cell do not exist but arise as optical artefacts from looking through
      semi-transparent combs.

PMID- 15257391
TI  - High precision during food recruitment of experienced (reactivated) foragers in
      the stingless bee Scaptotrigona mexicana (Apidae, Meliponini).
AB  - Several studies have examined the existence of recruitment communication
      mechanisms in stingless bees. However, the spatial accuracy of location-specific
      recruitment has not been examined. Moreover, the location-specific recruitment of
      reactivated foragers, i.e., foragers that have previously experienced the same
      food source at a different location and time, has not been explicitly examined.
      However, such foragers may also play a significant role in colony foraging,
      particularly in small colonies. Here we report that reactivated Scaptotrigona
      mexicana foragers can recruit with high precision to a specific food location.
      The recruitment precision of reactivated foragers was evaluated by placing
      control feeders to the left and the right of the training feeder (direction
      precision tests) and between the nest and the training feeder and beyond it
      (distance-precision tests). Reactivated foragers arrived at the correct location
      with high precision: 98.44% arrived at the training feeder in the direction
      trials (five-feeder fan-shaped array, accuracy of at least +/-6 degrees of
      azimuth at 50 m from the nest), and 88.62% arrived at the training feeder in the
      distance trials (five-feeder linear array, accuracy of at least +/-5 m or +/-10%
      at 50 m from the nest). Thus, S. mexicana reactivated foragers can find the
      indicated food source at a specific distance and direction with high precision,
      higher than that shown by honeybees, Apis mellifera, which do not communicate
      food location at such close distances to the nest.

PMID- 15257393
TI  - [Long-term changes in peripheral blood leukocyte and lymphocyte populations in
      ENT-carcinoma patients. A flow cytometric study in 346 ENT-carcinoma patients and
      31 healthy controls].
AB  - BACKGROUND AND AIM: The aim of this investigation was the quantification of
      leukocyte/lymphocyte populations in the peripheral blood of ENT-carcinoma
      patients before and long after therapy. PROBANDS AND METHOD: PBL T-lymphocytes
      and NK-cells were examined in 346 patients and 31 controls using flow cytometry.
      In 248 participants additional populations of leukocytes, monocytes,
      granulocytes, lymphocytes in toto, CD4+- and CD8+-lymphocytes, CD4+8+
      lymphocytes, B-lymphocytes, activated T-lymphocytes, NK-cells and CD3+56+-T
      lymphocytes were studied. RESULTS: We demonstrated a long-term reduction in T
      lymphocytes (CD4+-lymphocytes) in patients more than 10 years after receiving
      therapy, caused mainly, but not solely, by radio/chemotherapy. We also showed a
      long-term, significant increase in NK-cells after more than 10 years in patients
      following therapy without renewed carcinoma in comparison to controls, patients
      prior to therapy or patients with a recurrence of carcinoma. CONCLUSIONS: Due to
      long-term deficits in CD4+-lymphocytes, and considering the possible protective
      effect of NK-cells in treated patients, an immune-supportive therapy is
      recommended.

PMID- 15257394
TI  - [MRT sequences as a database for a visual articulatory model].
AB  - Articulatory models can be used in phoniatrics for the visualisation of speech
      disorders, and can thus be used in teaching, the counselling of patients and
      their relatives, and in speech therapy. The articulatory model developed here was
      based on static MRI data of sustained sounds. MRI sequences are now being used to
      further refine the model with respect to speech movements. Medio-sagittal MRI
      sections were recorded for 12 consonants in the symmetrical context of the three
      point vowels [i:], [a:] and [u:] for this corpus. The recording-rate was eight
      images/s. The data show a strong influence of the vocalic context on the
      articulatory target-positions of all consonants. A method for the reduction of
      the MRI data for subsequent qualitative and quantitative analyses is presented.

PMID- 15257395
TI  - [Extra-abdominal desmoid tumors. Case report and literature review].
AB  - Musculoaponeurotic fibromatosis or desmoid tumors are rare. We report the case of
      a 57 year old woman with a slowly growing tumor behind the sternocleidomastoid
      muscle, which was completely removed. Histological examination confirmed the
      clinical suspicion of a desmoid tumor. Desmoid tumors are aggressive, locally
      infiltrating, non-metastasizing tumors with a high local recurrence. Genetic,
      endocrine and physical factors have been implicated as causative agents. The
      diagnosis is made histologically, reactive fibromatosis and fibrosarcoma must be
      eliminated in differential diagnosis. By the combination of different
      radiographic techniques, it is possible to describe the tumors and differentiate
      between vessels, nerves and bones. The therapy of the choice is the surgical
      resection. Adjuvant therapy, such as x-ray treatment, chemo- and hormone therapy,
      are indicated when the tumor is inoperable or too extensive for surgery.

PMID- 15257396
TI  - [Tissue-engineered cartilage in a prefabricated microvascularized flap].
AB  - INTRODUCTION: In reconstructive surgery, the integration of tissue-engineered
      cartilage in a prefabricated free flap may make it possible to generate flaps
      combining a variety of tissue components to meet the special requirements of a
      particular defect. The aim of the present study was to establish the technique of
      prefabricating a microvascular free flap by implanting a vessel loop under a skin
      flap in a rabbit model. The second aim was to gather experience with
      prelaminating the flap with autologous tissue-engineered cartilage in terms of
      matrix development, inflammatory reaction and host-tissue interaction. METHODS:
      The microvascular flap was created by implanting a vessel loop under a random
      pattern abdominal skin flap. The tissue-engineered cartilage constructs were made
      by isolating chondrocytes from auricular biopsies. Following a period of
      amplification, the cells were seeded onto a non-woven scaffold made of a
      hyaluronic acid derivative and cultivated for 2-3 weeks. One cell-biomaterial
      construct was placed beneath the prefabricated flap, and the others were placed
      subcutaneously under the abdominal skin and intermuscularly at the lower
      extremity. In addition, a biomaterial sample without cells was placed
      subcutaneously as a control. All implanted specimens were left in position for 6
      or 12 weeks. After explantation, the specimens were examined by histological and
      immunohistological methods. The prefabricated flap was analyzed by angiography.
      RESULTS: The prefabricated flaps showed a well-developed network of blood vessels
      formed by neovascularization between the implanted vessel loop and the original
      random-pattern blood supply. The tissue-engineered constructs remained stable in
      size and showed signs of tissue similar to hyaline cartilage, as evidenced by the
      expression of cartilage-specific collagen type II and proteoglycans. No hints of
      inflammatory reactions were observed. CONCLUSION: These results show the
      potential of prefabricated flaps as custom-made flaps for reconstructive surgery
      in difficult circumstances, more or less independent of anatomical prerequisites.
      Cartilage tissue engineering provides a 3-dimensional structure with minimal
      donor-site morbidity.

PMID- 15257397
TI  - [Squamous cell carcinoma of the external ear. A carcinoma of old age which
      requires individualized therapy planning].
AB  - METHODS: Data for all patients with ear malignancies being operated in our
      department between August 1988 and March 2001 were retrospectively analyzed for
      tumor localisation, stage, biometric data, anesthesiological risk factors,
      therapy and recurrence of the disease. RESULTS: Thirty of 79 patients (29 male,
      one female; average age 77.2 years, range 54-99 years) with cutaneous
      malignancies of the external ear were diagnosed as SCC ( n=32 SCC). A total of 17
      SCC were smaller than 2 cm, 12 were between 2-5 cm, and three were larger than 5
      cm. Only two patients had regional nodal disease, none had distant metastases.
      The anesthesiological risk was estimated according to the recommendations of the
      American Society of Anesthesiologists (ASA); 16/30 patients were classified as
      group 3 or 4, having severe general disease with a decrease in vitality or even
      vital risks. A total of 24 SSC were primarily operated under local anesthesia.
      Depending on histology, localisation and size of the SCC local excision, partial
      or total removal of the auricle was performed. In the remaining 8/32 cases, the
      primary intervention was performed under general anesthesia, mostly in
      combination with an ipsilateral neck dissection and a superficial parotidectomy.
      In 8/32 cases, the SCC had to be re-operated after primary R1 resection.
      Altogether, eight patients received radiotherapy. In 5/32 cases there was a
      recurrence of the disease. The average follow-up period of the 13 patients who
      are still alive is 50 months (17-113). One patient died as a result of the
      metastasized SCC and 16 patients died due to other diseases. DISCUSSION:
      Considering the high age and the age-associated general diseases of the patients
      with SCC of the auricle, differentiation between a radical concept of therapy and
      its risks and possible therapy-related damage is important. Therefore, individual
      concepts such as partial removal of the pinna without neck dissection and
      parotidectomy for the N(0) stage are justified if relevant anesthesiological risk
      factors have to be taken into account.

PMID- 15257398
TI  - [Thermal irritation of the organ of equilibrium by means of heat radiation
      (NIR)].
AB  - BACKGROUND AND OBJECTIVE: Convection and conduction are the main factors involved
      in caloric response. Heat radiation has also been discussed as an important
      factor. The present work tests whether heat radiation is an essential part of the
      caloric response and whether caloric irritation of the semicircular canals is
      possible using two sources with a different near infrared (NIR) spectrum. In
      addition, we tested whether it is possible to induce a detectable nystagmus
      reaction using either NIR-radiation sources. RESULTS: NIR is able to penetrate
      bone tissue. The temperature elevation in dry and wet bones was almost
      immediately registered. With high optical power, specific temperature maxima
      could be seen by focal and selective broad spectrum and monochromatic NIR
      irritation of the three semicircular canals. Nystagmus could be generated after
      using both NIR emission sources in five probands. CONCLUSIONS: NIR generates
      temperature differences and nystagmus. By using a broad scale as well as a
      monochromatic NIR-emission source, it is possible to generate a nystagmus. The
      procedure of NIR-irritation occurs without physical contact, is painless and
      quiet.

PMID- 15257399
TI  - [A violent gagging response to small cysts on the arytenoid cartilage].

PMID- 15257400
TI  - [Prolactinoma of the sphenoid sinus. Case report and literature review].
AB  - In this case study, we report on a patient complaining of headache who, after CT
      and MRI, was found to have a neoplasia of the left sphenoid sinus. After a
      transnasal biopsy and histological examination, a prolactinoma was diagnosed.
      Based on this case, we discuss important aspects of tumor biology, diagnostic
      procedures, histology as well as differential diagnosis. Prolactinoma has to be
      considered as a differential diagnose in all sphenoid sinus neoplasias with close
      contact to the pituitary gland.

PMID- 15257401
TI  - [Severe complications after endonasal nasal sinus surgery. An unresolved
      problem].
AB  - Functional endoscopic sinus surgery is one of the most common procedures in our
      field. Despite modern techniques, major and even fatal complications may occur.
      We describe 3 cases of unilateral blindness due to retrobulbar hematoma and one
      case of an internal carotid artery injury with fatal outcome.

PMID- 15257402
TI  - [Unusually long latency before the appearance of Frey's syndrome after
      parotidectomy].
AB  - We report on an unusual case of Frey's syndrome. A 45 year old male patient
      presented with gustatory sweating 14 years after parotidectomy. The sialography
      showed a post-parotidectomy status without any pathologic findings. The MRI also
      showed a normal rest-parenchyma of the parotid gland without any pathologic
      findings. Minor's starch iodine test [14], confirmed the gustatory sweating in
      the left preauricular area. Frey's syndrome can appear with a latency of 14 years
      postoperative or post-trauma. The pathogenic mechanism and the curative therapy
      for this auriculotemporal-syndrome are still unsolved.

PMID- 15257403
TI  - [Leukocytoclastic vasculitis].
AB  - Leukocytoclastic vasculitis (LcV) is the most common form of cutaneous
      vasculitis. Often LcV results from deposition of immune complexes in the vascular
      wall. When IgA is the dominant immunoglobulin in these complexes, systemic
      involvement is likely (Henoch-Schonlein purpura), being more severe in adults.
      LcV in which immune complexes are composed of IgG or IgM are more often limited
      to the skin and may additionally show minor systemic involvement. In other forms
      of LcV additional pathophysiological factors play a role. LcV can also be a
      presenting or accompanying symptom of severe systemic ANCA-associated vasculitis.
      In some cases, LcV is a sign of bacteriemia. The aim of diagnostic procedures is
      to determine the specific type of vasculitis and degree of systemic involvement
      as well as possible causes. If no trigger or cause can be found, uncomplicated
      cases of LcV should be treated symptomatically. Corticosteroids are indicated at
      initial signs of necrosis or ulceration. Chronic recurrent LcV may respond to
      dapsone or colchicine. Severe systemic vasculitis requires immunosuppressive
      therapy.

PMID- 15257404
TI  - [Gastrointestinal stromal tumor of the abdominal wall. An unusual localization of
      a rare tumor].
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of
      the gastrointestinal tract. We describe here for the first time a patient with a
      huge GIST of the abdominal wall without any relation to the gastrointestinal
      tract, omentum, or mesentery. With regard to the size of 24 cm and a low mitotic
      index, this GIST is considered an intermediate risk for metastasis. Radical
      surgical resection was performed with negative pathologic resection margins. The
      classic immunohistochemical phenotype of the tumor described facilitates the
      differential diagnosis to exclude abdominal desmoid tumor and solitary fibrous
      tumor (SFT). In the case of metastasis, therapeutic nihilism no longer seems
      justified with the availability of imatinib, a tyrosine kinase inhibitor, which
      shows encouraging results in the therapy of metastatic GIST.

PMID- 15257407
TI  - Uterine arteriovenous malformation.
AB  - INTRODUCTION: Uterine arteriovenous malformations are very rare and potentially
      life-threatening. They can present with menorrhagia, postpartum bleeding,
      postmenopausal bleeding, an asymptomatic mass, or congestive heart failure. CASE
      REPORT: We present a 37-year-old woman with massive uterine bleeding that started
      abruptly 3 weeks after D and C and was found to be due to arteriovenous
      malformations.

PMID- 15257405
TI  - [Inhaled nitric oxide for the treatment of ARDS].
AB  - Acute respiratory distress syndrome (ARDS) is characterized by perfusion in favor
      of non-ventilated areas of the lungs as the main cause of intrapulmonary right-to
      left shunt and hypoxemia. Therapeutic interventions to selectively influence
      pulmonary perfusion in ARDS became possible with the introduction of inhaled
      nitric oxide (iNO), which provided a way not only to reduce pulmonary
      hypertension, but also to acutely improve ventilation-perfusion mismatch, and
      thus to treat severe hypoxemia. Clinical studies in ARDS demonstrated that the
      combination of iNO with other interventions, such as positive end-expiratory
      pressure (PEEP) and prone positioning, yielded beneficial and additive effects on
      arterial oxygenation. Although randomized controlled trials of this concept have
      up to now failed to show an improved outcome, iNO is a valuable option for the
      treatment of severe refractory hypoxemia in ARDS patients.

PMID- 15257408
TI  - Human leukocyte antigen class II alleles and natural history of HPV 2/27/57
      induced common warts.
AB  - Epidemiological studies have demonstrated an association between HLA-DQB1*03
      alleles and the risk of cervical cancer induced by human papillomavirus (HPV). As
      persistence of HPV infection is required for developing cervical cancer, we
      wanted to elucidate the role of HLA-class II allele polymorphisms in the
      persistence of common warts induced by HPV 2, HPV 27 or HPV 57. Therefore, we
      determined the distribution of HLA-DQA1, -DQB1, and -DRB1 alleles in 71 patients
      presenting with HPV 2/27/57-induced common warts which had persisted for at least
      18 months as well as in 92 individuals who had never suffered from common warts
      or whose warts had healed in less than 18 months. Among patients with long
      lasting warts, the carriership frequencies and allele frequencies of DQA1*0301,
      DQB1*0301, DRB1*07 and DRB1*09 were higher, and the allele frequencies of
      DQA1*0501, DQB1*0603, DRB1*01 and DRB1*03 were lower. Statistically significant
      differences (Bonferroni adjusted Fisher's exact test) were found for carriership
      frequency of DQA1*0301 (46.5 vs 21.7%, P = 0.013) and for carriership frequency
      (18.3 vs 1.1%, P = 0.0015) and allele frequency (12 vs 0.5%, P = 0.000013) of
      DQB1*0301. A greater proportion of patients with long-lasting warts than of
      subjects without persistent warts were homozygous at the DQA1 (14.1 vs 6.5%) and
      DQB1 (16.9 vs 8.6%) gene loci. These results suggest that the natural history of
      cutaneous HPV 2/27/57-induced common warts may be modulated by allele
      polymorphisms at the HLA-DQA1 and HLA-DQB1 gene loci.

PMID- 15257409
TI  - Management strategies for treatment of the trapped fourth ventricle.
AB  - BACKGROUND: An isolated or trapped fourth ventricle (TFV) is an occasional,
      serious sequela of hemorrhagic, infectious, or inflammatory conditions of the
      central nervous system. The TFV usually occurs after successful shunting of the
      lateral ventricles. It may be heralded by delayed clinical deterioration after an
      initial period of symptomatic improvement. The typical clinical findings suggest
      an expanding posterior fossa mass lesion. Surgical treatments include CSF
      diversionary procedures as well as open and endoscopic approaches. Complications
      related to the treatment of the TFV are common and relate to catheter obstruction
      and cranial nerve or brainstem dysfunction. METHODS: The author reviews the
      clinical features, pathophysiology, and available treatment options for the TFV,
      with special reference to complication avoidance and advances in ventriculoscopy
      and frameless stereotaxy. CONCLUSIONS: Treatment of the TFV remains a formidable
      challenge. However, prompt recognition and intervention may aid in the
      preservation of life and neurological function.

PMID- 15257410
TI  - Management of pyopagus conjoined twins.
AB  - INTRODUCTION: Approximately 18% of conjoined twins (1 in 200,000 live births) are
      joined at the sacrum ("pyopagus"). As the joined structures are not life
      threatening, there is generally a good prognosis, with time for investigation and
      planning of operative separation. CASE REPORT: This paper reports on the
      management of pyopagus twin girls, the first in the UK delivered at 36 weeks by
      Caesarean section. The diagnosis had been made by ultrasound at 12 weeks' and
      confirmed by MRI scan at 26 weeks' gestation. Each twin had wasting and weakness
      below one knee, but no deficit in the other leg. The perineum had two urethras
      but only one anus. One infant had a colostomy in the immediate neonatal period.
      With appropriate further imaging, surgery was planned in two stages. First, a
      balloon expander was inserted in the bridging area. At 3 months of age a team
      comprising Plastic, Paediatric and Neurosurgeons undertook the definitive
      separation. DISCUSSION: Details of the multidisciplinary planning, operative
      separation and follow-up of these two children will be discussed.

PMID- 15257411
TI  - Vascular endothelial and basic fibroblast growth factor serum levels in patients
      with Behcet's disease.
AB  - Behcet's disease (BD) is a systemic vasculitis of unknown aetiology. Its
      pathogenesis is related to endothelial cell dysfunction, humoral immune defects,
      and immune system dysregulation. The aim of this study was to investigate the
      possible role of vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) in the pathogenesis of BD. We also investigated whether
      disease activity, age, or duration of BD correlates with VEGF and bFGF. We
      studied 33 patients and 20 healthy controls. Vascular endothelial growth factor
      and bFGF serum levels were measured by enzyme-linked immunosorbent assay. We
      measured acute phase reactants, including erythrocyte sedimentation rate (ESR)
      and C-reactive protein (CRP). The mean serum VEGF level was significantly higher
      in patients with BD (398.8+/-222.2 pg/ml) than the control group (193.0+/-122.4
      pg/ml) (P=0.002). The levels were similar in both active and inactive BD
      (P=0.675) but did not correlate with disease duration, CRP, ESR, or age (P>0.05
      for each). The bFGF was below detection limits in 18 of 33 patients with BD and
      ten of 20 controls, and its mean serum level was higher in BD patients (42.4+/
      76.9 pg/ml) than controls (29.0+/-9.1 pg/ml), but this difference was not
      statistically significant (P=0.232). The bFGF levels were similar in both active
      and inactive BD (P=0.09) and, in patients, correlated with disease duration and
      CRP (r=0.58, P=0.02; r=-0.57, P=0.02, respectively) but not with ESR or age
      (P>0.05 for each). Vascular endothelial growth factor may be more important in
      the pathogenesis of BD than bFGF. Neither growth factor is an activity criterion
      or inflammatory marker in BD.

PMID- 15257412
TI  - Hydrotherapy, balneotherapy, and spa treatment in pain management.
AB  - The use of water for medical treatment is probably as old as mankind. Until the
      middle of the last century, spa treatment, including hydrotherapy and
      balneotherapy, remained popular but went into decline especially in the Anglo
      Saxon world with the development of effective analgesics. However, no analgesic,
      regardless of its potency, is capable of eliminating pain, and reports of life
      threatening adverse reactions to the use of these drugs led to renewed interest
      in spa therapy. Because of methodologic difficulties and lack of research
      funding, the effects of 'water treatments' in the relief of pain have rarely been
      subjected to rigorous assessment by randomised, controlled trials. It is our
      opinion that the three therapeutic modalities must be considered separately, and
      this was done in the present paper. In addition, we review the research on the
      mechanism of action and cost effectiveness of such treatments and examine what
      research might be useful in the future.

PMID- 15257413
TI  - Functional characterisation and transcriptional regulation of the KlHEM12 gene
      from Kluyveromyces lactis.
AB  - Cloning, sequencing and functional analysis of the Kluyveromyces lactis KlHEM12
      gene and its upstream region are reported. The gene encodes for a protein that is
      highly homologous to uroporphyrinogen decarboxylases from different organisms and
      complements its mutation in Saccharomyces cerevisiae. Secondary structure
      prediction allows outlining a topology diagram which is compatible with a
      (beta/alpha)8-barrel structure. A K. lactis haploid strain carrying a null allele
      of KlHEM12 showed decreased growth in media not supplemented with hemin
      (ferriprotoporphyrin IX) and red-fluorescent colonies due to the accumulation of
      porphyrins. KlHEM12 expression was analysed by Northern blot and promoter fusion
      to the reporter lacZ gene. Transcription of this gene is not under heme or
      glucose repression and it is slightly induced by non-fermentable carbon sources
      through the Hap2/3/4/5 complex.

PMID- 15257414
TI  - [Pulmonary hypertension in chronic myeloproliferative disorders].
AB  - We report on three autopsy cases with clinical and morphological evidence of
      pulmonary hypertension and concurrent myeloproliferative disorders. Massive
      accumulations of pleomorphic, atypical megakaryocytes and thrombotic material are
      found within the pulmonary capillary beds. Morphometrical studies allowed us to
      identify on average 1,293.4 (1,145.8-1,401) megakaryocytes per one square
      centimetre lung tissue (standard value: 25 megakaryocytes/cm(2) lung tissue). The
      lungs of the controls with unaffected parenchyma show smaller numbers of
      megakaryocytes. It seems highly unlikely that these haematopoietic cells
      originate in lung capillaries in the absence of morphological correlates.
      Recurrent chronic microemboli consisting of megakaryocytes and thrombocytes could
      be held responsible for the development of secondary chronic pulmonary
      hypertension. Our observations suggest that pulmonary hypertension associated
      with chronic myeloproliferative disorders should be classified into the fourth
      group of the EVIAN-classification of pulmonary hypertension.

PMID- 15257415
TI  - [Proposal for the classification of the periprosthetic membrane from loosened hip
      and knee endoprostheses].
AB  - After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10
      percent of all patients, requiring elaborate revision surgery. A periprosthetic
      membrane is routinely found between bone and loosened prosthesis. Further
      histomorphological examination allows determination of the etiology of the
      loosening process. Aim of this study is the introduction of clearly defined
      histopathological criteria for a standardized evaluation of the periprosthetic
      membrane. Based on histomorphological criteria and polarized light microscopy,
      four types of the periprosthetic membrane were defined: periprosthetic membrane
      of wear particle type (type I), periprosthetic membrane of infectious type (type
      II), periprosthetic membrane of combined type (type III), periprosthetic membrane
      of indifferent type (type IV). Periprosthetic membranes of 268 patients were
      analyzed according to the defined criteria. The correlation between
      histopathological and microbiological diagnosis was high (89%, p<0,001), the
      inter-observer reproducibility was sufficient (95%). This classification system
      enables a standardized diagnostic procedure and therefore is a basis for further
      studies concerning the etiology of and pathogenesis of prosthesis loosening.

PMID- 15257417
TI  - Three-dimensional computer-assisted reconstruction of ductal plate in the rat
      embryo (Carnegie stages 19-23).
AB  - In bile duct morphogenesis it has been established that the extrahepatic bile
      ducts in human originate from hepatic diverticulum while intrahepatic bile ducts
      arise from the ductal plate (DP), a network of primitive biliary epithelium that
      develops in the periportal connective tissue. The aim of this work was to
      reconstruct in rat embryos, stages 19-23, the three-dimensional (3D) distribution
      of the DP by means of a computer-assisted method. Six specimens, stages 19-23,
      fixed, dehydrated and paraffin-embedded, were submitted to serial histological
      sections and stained by hematoxylin-eosin and Heidenhain techniques. The images
      were directly digitalized with a CCD camera. The serial views were aligned
      anatomically by software and the data were analyzed following segmentation and
      thresholding. At stage 19, the DP was not yet organized. The periportal mesoderm
      (M) was gaining ground with some cords of cubic cells evoking primitive ductal
      cells. At stage 20, a row of ductal cubic cells went around the transverse portal
      sinus at the junction between M and liver cells. At stage 21, the DP developed at
      the periphery of periportal connective tissue and appeared in direct continuity
      with the hepatic duct (HDu). Four evaginations emerged from the DP and were
      growing up in the hepatic parenchyma. At stage 23, the DP appeared as a large
      network in continuity with the HDu located at the periphery of periportal M and
      presenting several evaginations radiating in the liver parenchyma. This work in
      the rat embryo permits the clear visualization of the development of the
      junctional zone in the hepatic hilum. Three phenomena are observed: (1) proximal
      left and right hepatic ducts and their segmental branches are derived from DP and
      not from the HDu; (2) the extrahepatic biliary system is in contact with the
      developing hilar ducts; (3) ductal maturation begins at the hilum and proceeds
      centrifugally. These observations are of great relevance in explaining
      pathological changes appearing at the hepatic hilum of neonates: hepatic
      polycystic disease, intrahepatic bile duct agenesis or atresia, and cyst of the
      extrahepatic bile duct.

PMID- 15257418
TI  - Comparison of different SUV-based methods for monitoring cytotoxic therapy with
      FDG PET.
AB  - PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is
      a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited
      data available, a standard imaging protocol for the prediction of tumour response
      has not yet been approved. The aim of this study was to compare commonly applied
      imaging protocols and calculations of the standardised uptake value (SUV) for the
      early prediction of histopathological response to chemotherapy. METHODS: Serial
      FDG PET scans of 43 patients with gastric carcinomas were retrospectively
      analysed. All patients received two consecutive scans (one bed position at 40 min
      p.i. and four bed positions at 90 min p.i.) at baseline and during the first
      cycle of cisplatinum-based chemotherapy. Reconstruction of the images was
      performed by filtered back-projection (FBP) and using an iterative algorithm
      (OSEM). SUVs were calculated with and without correction for the blood glucose
      level using normalisation by body weight, body surface area and lean body mass.
      Relative percentage changes between SUVs at baseline and follow-up were
      calculated and analysed for their potential to predict histopathological response
      to chemotherapy (ROC analysis). Response was defined as less than 10% viable
      tumour cells in the tumour specimen obtained by surgery 3-4 weeks after the
      completion of chemotherapy. RESULTS: Eight of 43 patients were histopathological
      responders to chemotherapy. The percentage changes in SUV(body weight) for
      responders and non-responders were -52.2 (+/-13.2) and -25.2 (+/-15.2), -54.7 (+/
      18.2) and -24.5 (+/-16.1), -53.9 (+/-24.2) and -22.7 (+/-21.3), and -56.7 (+/
      21.6) and -26.1 (+/-18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP
      and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each
      case). According to ROC analysis, neither the scan protocol nor correction for
      blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off
      value (approx. -40% change in tumour SUV) for the prediction of response.
      Normalisation of SUVs by body surface area or lean body mass instead of body
      weight yielded essentially identical results. CONCLUSION: In gastric carcinomas
      the prediction of response to chemotherapy on the basis of relative tumour SUV
      changes is not essentially influenced by any of the methodological variations
      investigated (time delay after FDG administration, acquisition protocol,
      reconstruction algorithm, normalisation of SUV). This demonstrates the robustness
      of FDG PET for therapeutic monitoring and facilitates the comparability of
      studies obtained at different institutions and with different protocols. However,
      whichever method is used for therapy monitoring with FDG PET, a highly
      standardised protocol must be observed to take the dynamics of tumour FDG uptake
      into account.

PMID- 15257419
TI  - Isolation and characterization of a novel intracellular glucosyltransferase from
      the acarbose producer Actinoplanes sp. CKD485-16.
AB  - A novel intracellular glucosyltransferase (GTase) was isolated from cells of
      Actinoplanes sp. CKD485-16-acarbose-producing cells. The enzyme was purified by
      DEAE-cellulose and G75-40 Sephadex chromatography. The molecular mass of the
      enzyme was estimated to be 62 kDa by SDS-polyacrylamide gel electrophoresis, and
      its isoelectric point (pI) was pH 4.3. The N-terminal sequence of the GTase
      consisted of NH(2)-Ser-Val-Pro-Leu-Ser-Leu-Pro-Ala-Glu-Trp. The optimum pH and
      temperature were 7.5 and 30 degrees C. The enzyme was stable in a pH range of 5.5
      9.0 and below 40 degrees C. Enzymatic reactions were performed by incubating the
      GTase with various substrates. The GTase converted acarbose into component C,
      maltose into trehalose, and maltooligosaccharides into maltooligosyl trehaloses.
      The reactions were reversible. Various acarbose analogs were tested as inhibitors
      against the GTase as a means to suppress component C formation. Valienamine was
      the most potent, with an IC(50) value of 2.4x10(-3) mM and showed a competitive
      inhibition mode.

PMID- 15257420
TI  - Purification, substrate specificity, and N-terminal amino acid sequence analysis
      of a beta-lactamase-free penicillin amidase from Alcaligenes sp.
AB  - A beta-lactamase-free penicillin amidase from Alcaligenes sp. active against
      various beta-lactams was purified to homogeneity. The enzyme can hydrolyze
      penicillin G to 6-amino penicillanic acid (6-APA) and furnish penicillin G from 6
      APA and phenyl acetic acid by condensation. The penicillin amidase is a
      heterodimer of subunit masses of 63 kDa and 22 kDa, respectively. Its isoelectric
      point is at pH 8.5. Cephalothin was found to be the best substrate. This is a
      novel type II penicillin amidase which shares the properties of both type II and
      type III enzymes. It is thermostable and, unlike penicillin amidase from A.
      faecalis, its stability remains unperturbed even in presence of reductant. An
      inhibition study by 2-hydroxy-5-nitro benzylbromide indicated the involvement of
      tryptophan in catalysis by the enzyme.

PMID- 15257421
TI  - Effect of hyperbaric stress on yeast morphology: study by automated image
      analysis.
AB  - The effects of hyperbaric stress on the morphology of Saccharomyces cerevisiae
      were studied in batch cultures under pressures between 0.1 MPa and 0.6 MPa and
      different gas compositions (air, oxygen, nitrogen or carbon dioxide), covering
      aerobic and anaerobic conditions. A method using automatic image analysis for
      classification of S. cerevisiae cells based on their morphology was developed and
      applied to experimental data. Information on cell size distribution and bud
      formation throughout the cell cycle is reported. The results show that the effect
      of pressure on cell activity strongly depends on the nature of the gas used for
      pressurization. While nitrogen and air to a maximum of 0.6 MPa of pressure were
      innocuous to yeast, oxygen and carbon dioxide pressure caused cell inactivation,
      which was confirmed by the reduction of bud cells with time. Moreover, a decrease
      in the average cell size was found for cells exposed for 7.5 h to 0.6 MPa CO2.

PMID- 15257422
TI  - Degradation of acrylic copolymers by white-rot fungi.
AB  - Various water-soluble homopolymers and copolymers of acrylamide (AAm) and acrylic
      acid (AA) which contained phenolic sites, such as guaiacol, lignin sulfonate (LS)
      and 3,4-dihydroxybenzoic acid (3,4-DHBA), were tested with regard to their
      degradability by white-rot fungi. Compared with Phanerochaete chrysosporium,
      Pleurotus ostreatus caused a significantly higher decrease in the average
      molecular weight ( Mw) of most of the copolymers and the homopolymer under the
      applied culture conditions. However, the Mw of poly(guaiacol/AAm) increased
      significantly during incubation with Pl ostreatus. P. chrysosporium was able to
      reduce only the Mw of the poly(LS/AA) to a significant degree and not that of the
      other polymers. The mineralization rate of AAm and AA copolymers and terpolymers
      of AAm, AA and phenolics (LS, 3,4-DHBA, guiacol), which were tested with P.
      ostreatus and Trametes versicolor, turned out to be low (0.8-3.2%). While the
      rates of mineralization were similar among all polymers, the decrease in
      radioactivity from the culture media was higher with the terpolymers bearing
      phenolic sites. UV spectra of the culture media revealed that the phenolic sites
      in the terpolymers were significantly degraded by both fungi. Obviously, the
      degradation of phenolics within the polymer chain caused a higher decrease in Mw
      but did not significantly increase the mineralization rate.

PMID- 15257424
TI  - Chemotaxis: the role of internal delays.
AB  - When exposed to certain chemoattractants, bacteria like Escherichia coli move up
      the concentration gradient[Delta inverted]c with a velocity kappa[delta
      inverted]c. Microscopically, E. coli moves at constant speed when it's flagellum
      is rotating counter-clockwise (ccw) and tumbles when the rotation is clockwise
      (cw). The lifetime of a ccw interval, tau+, is a function of the concentration c(
      t') experienced at earlier times. The corresponding response function was
      measured long ago by Berg and co-workers. We present here a detailed description
      of the motion taking place during one ccw interval. This gives an explicit
      formula relating the chemotactic coefficient kappa to the response function; the
      formula has some surprising features.

PMID- 15257423
TI  - 2004 Nomenclature for the chicken major histocompatibility (B and Y) complex.
AB  - The first standard nomenclature for the chicken (Gallus gallus) major
      histocompatibility (B) complex published in 1982 describing chicken major
      histocompatibility complex (MHC) variability is being revised to include
      subsequent findings. Considerable progress has been made in identifying the genes
      that define this polymorphic region. Allelic sequences for MHC genes are
      accumulating at an increasing rate without a standard system of nomenclature in
      place. The recommendations presented here were derived in workshops held during
      International Society of Animal Genetics and Avian Immunology Research Group
      meetings. A nomenclature for B and Y (Rfp-Y) loci and alleles has been developed
      that can be applied to existing and newly defined haplotypes including
      recombinants. A list of the current standard B haplotypes is provided with
      reference stock, allele designations, and GenBank numbers for corresponding MHC
      class I and class IIbeta sequences. An updated list of proposed names for B
      recombinant haplotypes is included, as well as a list of over 17 Y haplotypes
      designated to date.

PMID- 15257425
TI  - Hydrodynamic effects in fast AFM single-molecule force measurements.
AB  - Atomic force microscopy (AFM) allows the critical forces that unfold single
      proteins and rupture individual receptor-ligand bonds to be measured. To derive
      the shape of the energy landscape, the dynamic strength of the system is probed
      at different force loading rates. This is usually achieved by varying the pulling
      speed between a few nm/s and a few microm/s, although for a more complete
      investigation of the kinetic properties higher speeds are desirable. Above 10
      microm/s, the hydrodynamic drag force acting on the AFM cantilever reaches the
      same order of magnitude as the molecular forces. This has limited the maximum
      pulling speed in AFM single-molecule force spectroscopy experiments. Here, we
      present an approach for considering these hydrodynamic effects, thereby allowing
      a correct evaluation of AFM force measurements recorded over an extended range of
      pulling speeds (and thus loading rates). To support and illustrate our
      theoretical considerations, we experimentally evaluated the mechanical unfolding
      of a multi-domain protein recorded at 30 microm/s pulling speed.

PMID- 15257426
TI  - Acoustic manipulation of small droplets.
AB  - Surface acoustic waves are used to actuate and process smallest amounts of fluids
      on the planar surface of a piezoelectric chip. Chemical modification of the chip
      surface is employed to create virtual wells and tubes to confine the liquids.
      Lithographically modulated wetting properties of the surface define a fluidic
      network, in analogy to the wiring of an electronic circuit. Acoustic radiation
      pressure exerted by the surface wave leads to internal streaming in the fluid and
      eventually to actuation of small droplets along predetermined trajectories. This
      way, in analogy to microelectronic circuitry, programmable biochips for a variety
      of assays on a chip have been realized.

PMID- 15257427
TI  - Identification of the regulatory proteins in human pancreatic cancers treated
      with Trichostatin A by 2D-PAGE maps and multivariate statistical analysis.
AB  - In this paper, principal component analysis (PCA) is applied to a spot quantity
      dataset comprising 435 spots detected in 18 samples belonging to two different
      cell lines (Paca44 and T3M4) of control (untreated) and drug-treated pancreatic
      ductal carcinoma cells. The aim of the study was the identification of the
      differences occurring between the proteomic patterns of the two investigated cell
      lines and the evaluation of the effect of the drug Trichostatin A on the protein
      content of the cells. PCA turned out to be a successful tool for the
      identification of the classes of samples present in the dataset. Moreover, the
      loadings analysis allowed the identification of the differentially expressed
      spots, which characterise each group of samples. The treatment of both the cell
      lines with Trichostatin A therefore showed an appreciable effect on the proteomic
      pattern of the treated samples. Identification of some of the most relevant spots
      was also performed by mass spectrometry.

PMID- 15257428
TI  - Direct determination of copper in urine using a sol-gel optical sensor coupled to
      a multicommutated flow system.
AB  - In this work, a multicommutated flow system incorporating a sol-gel optical
      sensor is proposed for direct spectrophotometric determination of Cu(II) in
      urine. The optical sensor was developed by physical entrapment of 4-(2
      pyridylazo)resorcinol (PAR) in sol-gel thin films by means of a base-catalysed
      process. The immobilised PAR formed a red 2:1 complex with Cu(II) with maximum
      absorbance at 500 nm. Optical transduction was based on a dual-colour light
      emitting diode (LED) (green/red) light source and a photodiode detector. The
      sensor had optimum response and good selectivity towards Cu(II) at pH 7.0 and its
      regeneration was accomplished with picolinic acid. Linear response was obtained
      for Cu(II) concentrations between 5.0 and 80.0 microg L(-1), with a detection
      limit of 3.0 microg L(-1) and sampling frequency of 14 samples h(-1).
      Interference from foreign ions was studied at a 10:1 ( w/ w) ion:Cu(II) ratio.
      Results obtained from analysis of urine samples were in very good agreement with
      those obtained by inductively coupled plasma mass spectrometry (ICP-MS); there
      was no significant differences at a confidence level of 95%.

PMID- 15257429
TI  - Ferrocene-containing polyelectrolyte multilayer film-covered electrodes:
      electrocatalytic determination of ascorbic acid and use of inner blocking layers
      to improve the upper detection limit of the electrodes.
AB  - A multilayer film composed of ferrocene(Fc)-appended poly(allylamine
      hydrochloride) (Fc-PAH) and poly(potassium vinylsulfate) (PVS) has been prepared
      on the surface of a gold(Au) electrode by using a layer-by-layer self-assembly
      technique. Fc-containing polyelectrolyte multilayer (PEM) film-modified
      electrodes can electrochemically catalyze the oxidation of ascorbic acid
      successfully. For a 2 (Fc-PAH/PVS) bilayer-covered electrode the catalytic
      current increased linearly with increasing concentration of ascorbic acid over
      the concentration range 6 micromol L(-1)-3 mmol L(-1). To extend the dynamic
      range for ascorbic acid, the surface of the Au electrode was first covered with a
      (PAH/PVS)(2) film on which an additional (Fc-PAH/PVS)(5) film was coated. This
      strategy successfully extended the dynamic range of the electrode up to 25 mmol
      L(-1) ascorbic acid, because the (PAH/PVS)(2) layer blocked access of ascorbic
      acid to the electrode surface. The upper detection limit of the (PAH/PVS)(2) (Fc
      PAH/PVS)(5) film-modified electrode is much higher than those of Fc-based
      ascorbic acid sensors reported so far. Electron transfer is diffusion-controlled
      within the (PAH/PVS)(2)(Fc-PAH/PVS)(5) film.

PMID- 15257430
TI  - Cloning and characterization of a gene encoding the gamma-butyrolactone
      autoregulator receptor from Streptomyces clavuligerus.
AB  - With primers designed for the conserved region of the gamma-butyrolactone
      autoregulator receptor proteins from Streptomyces species, PCR using the
      Streptomyces clavuligerus genome DNA as a template gave a clear band of 100 bp,
      the sequence of which revealed high similarity to the expected region of a
      receptor gene. By Southern blot and colony hybridization with the 100-bp insert
      as a probe, plasmid pSCA, harboring a 4.2 kb- SalI fragment, was obtained.
      Sequence analysis on the insert revealed a 702-bp ORF encoding a protein with a
      moderate similarity (identity, 33-43%; similarity, 51-62%) to known gamma
      butyrolactone autoregulator receptor proteins from Streptomyces sp. The ORF was
      named scaR ( S. clavuligerus autoregulator receptor). The scaR/pET-3d plasmid was
      constructed for overexpression of the recombinant ScaR protein (rScaR) in
      Escherichia coli, and the rScaR protein was purified to homogeneity by DEAE-ion
      exchange HPLC. The molecular mass of the purified rScaR protein was determined to
      be 27 kDa as determined by SDS-PAGE, and 54 kDa by gel filtration HPLC under
      nondenatured conditions at a low protein concentration, indicating that the
      majority of the native ScaR is present in the form of a dimer, although rScaR
      tended to aggregate into a higher molecular form of 230 kDa at a high protein
      concentration. A binding assay with tritium-labeled autoregulators indicated that
      IM-2 type compounds with a long C2 side chain were the most effective ligands for
      rScaR, demonstrating for the first time that the beta-lactam producer S.
      clavuligerus contains a gene for the gamma-butyrolactone autoregulator receptor.

PMID- 15257431
TI  - Faucets as a reservoir of endemic Pseudomonas aeruginosa colonization/infections
      in intensive care units.
AB  - OBJECTIVE: To evaluate the role of faucets as a reservoir for Pseudomonas
      aeruginosa colonization/infection of patients hospitalized in intensive care
      units (ICUs). DESIGN: Prospective epidemiological investigation performed during
      a nonepidemic period of 1 year. The inner part of the ICU faucets were swabbed
      for P. aeruginosa. Data were recorded on all patients with at least one culture
      of a clinical specimens positive for P. aeruginosa. Pulsed-field gel
      electrophoresis was used to characterize the strains. SETTING: Five ICUs of a
      university hospital which are supplied by two separate water distribution
      networks. PATIENTS: During a 1-year period 132 cases were investigated. RESULTS:
      In 42% of cases (56/132) there were isolates identical to those found in the
      faucets, with a total of nine different genotypes. Among the nine genotypes
      isolated from both patients and faucets one of them, the most prevalent, was
      isolated in the two networks and in 30 cases. The other eight genotypes were
      recovered almost exclusively from either one (three genotypes in 12 cases) or the
      other (five genotypes in 12 cases) network and from the patients in the
      corresponding ICUs. CONCLUSIONS: These results suggest that the water system of
      the ICUs was the primary reservoir of patient's colonization/infection with P.
      aeruginosa in a substantial proportion of patients, although the exact mode of
      acquisition could not be determined.

PMID- 15257432
TI  - [Treatment of congenital scoliosis with the vertical expandable prosthetic
      titanium rib implant].
AB  - Children with congenital thoracic scoliosis associated with fused ribs and
      unilateral unsegmented bars adjacent to convex hemivertebrae will invariably have
      curve progression without treatment. It is assumed that the unilateral
      unsegmented bars do not grow and therefore early spinal fusion has been performed
      in the past with consecutive short thoracic spines and loss of lung volume. A new
      surgical technique is based on an indirect deformity correction and enlargement
      of the thorax via a longitudinal implant, the vertical expandable prosthetic
      titanium rib (VEPTR). The length of the thoracic spine after VEPTR implantation
      was analyzed in 21 children with an average follow-up of 4.2 years. Eighteen
      children did not have any prior surgery while three had already undergone spinal
      fusion. Using a 3-D analysis of computed tomography, a significant growth of the
      concave (7.9 mm/7.1% increase per year) and convex (8.3 mm/6.4%) side of the
      thoracic spine was found with no significant difference between sides. Unilateral
      unsegmented bars showed significant growth as well. Contrary to common knowledge,
      we were able to demonstrate the growth of the concave side of the thoracic spine
      and of the unilateral unsegmented bars after expansion thoracoplasty and VEPTR
      implantation.

PMID- 15257433
TI  - [Arthrodesis of the hip and its conversion].
AB  - Arthrodesis of the hip used to be an important means of treating painful and
      damaged hips. Increasing experiences in total hip replacement have led to
      restrictive indications for arthrodesis and to more and more total hip
      arthroplasty. Hip arthrodesis has limited indications today. It remains the
      treatment of choice in deteriorated, painful hip joints, especially in the case
      of contraindications and severe muscular deficits. The best position of the fused
      hip is 10 to 25 degrees flexion, 0 to 15 degrees external rotation, 0 to 10
      degrees abduction or 0 to 6 degrees adduction. The aim of the operation is a
      stable osteosynthesis which allows early mobilisation of the patient.
      Disturbances in walking patterns, mechanical overloading of neighbouring joints,
      such as the lumbar spine, ipsilateral knee or contralateral hip, often support a
      conversion from arthrodesis to total hip arthroplasty. The aim of the primary
      operation, therefore, is the preservation of the stabilizing pelvitrochanteric
      muscles and their insertions.

PMID- 15257434
TI  - Exploiting selective genotyping to study genetic diversity of resistance to
      Fusarium head blight in barley.
AB  - Numerous barley cultivars from around the world have been identified as potential
      sources of Fusarium head blight (FHB) resistance genes. All of these cultivars
      exhibit partial resistance, and several mapping studies have shown that
      resistance to FHB is controlled by multiple genes. Successful development of
      barley cultivars with high levels of FHB resistance will require combining genes
      from multiple sources. We characterized five potential new sources of FHB
      resistance ('AC Oxbow', 'Atahualpa', 'HOR211', 'PFC88209', and 'Zhedar#1') to
      determine if they contain new FHB resistance genes. Cluster analysis, using a set
      of 80 SSR markers distributed throughout the genome, showed that most of the new
      sources of resistance were not similar to three cultivars that have been used in
      previous FHB mapping studies ('Chevron', 'Frederickson', and 'Gobernadora'), with
      'Atahualpa' and 'HOR211' being the most dissimilar. By selective genotyping, we
      determined whether markers linked to six known FHB resistance quantitative trait
      loci (QTLs), discovered in other genotypes, explained variation for resistance in
      advanced breeding populations created from the new sources of resistance. Markers
      linked to four of the six known QTLs were associated with FHB severity in at
      least one of the populations. However, none of the six QTL regions were
      associated with variation for FHB severity in populations derived from crosses
      that utilized sources of resistance HOR211 or PFC88209. Selective genotyping is
      an efficient method for breeders to utilize current QTL information about disease
      resistance to search for new resistance genes.

PMID- 15257435
TI  - [Radical cystectomy and urinary diversion in elderly patients with increased
      comorbidity].
AB  - Radical cystectomy with urinary diversion is the accepted standard of care for
      invasive bladder cancer with orthotopic neobladders. It is the preferred method
      for bladder substitution in male and female patients and even in selected
      patients with locally advanced tumors. The complication rates for orthotopic
      bladder substitutes are similar to or lower than the morbidity rates after
      conduit formation or continent cutaneous diversion. Due to progress in
      perioperative management, intensive care and surgery, cystectomy is now part of
      the classical treatment options for bladder cancer in elderly patients, with
      acceptable morbidity rates. However, the indication for cystectomy in people
      older than 75 years should be based on a rigorous preoperative risk assessment
      (ASA status) and a life expectancy of more than 2 years independent of the tumor.
      Transurethral resection alone should be proposed only to patients with a poor
      performance status.

PMID- 15257436
TI  - [Primary progressive aphasia].
AB  - Primary progressive aphasia is a rare disease characterised by slow deterioration
      of language, which remains the leading symptom whereas other cognitive functions
      such as memory, orientation, judgement, and visual-spatial skills are relatively
      spared and mostly not affected until 5 to 7 years after disease onset. Structural
      imaging displays atrophy of the left temporal region which can also affect the
      frontal region or both hemispheres. Reduced neuronal activity in the left
      temporal lobe can be seen using functional imaging even before structural
      anomalies are detected. Neuropathological examination reveals neuronal cell loss
      and gliosis in the regions of atrophy which are sometimes accompanied by
      spongiform changes. T-positive neurons or plaques and neurofibrillary tangles are
      present in rare cases. A specific therapy is not known. Logopaedic therapy
      focussed on the main symptoms seems to stabilise linguistic abilities.

PMID- 15257437
TI  - [Function of the facial nerve after operative treatment of acoustic neurinomas.
      Influence of intraoperative monitoring].
AB  - The aim of this study was to evaluate the influence of intraoperative monitoring
      on the function of the facial nerve after surgical treatment of acoustic
      neurinomas, classified according to the grading system of Stennert. One hundred
      thirty patients were divided into two groups. The first group underwent surgery
      without intraoperative facial monitoring; the second group included
      intraoperative facial monitoring. Concerning degree of paresis, preoperatively
      there was no statistically significant difference between the two groups (group
      1: 0.77+/-1.5; group 2: 0.4+/-1.2). Despite structural preservation of the facial
      nerve, postoperative deterioration of its function was observed which
      consecutively improved postoperatively. Postoperatively, the mean degree of
      paresis increased to 4.4+/-3.0 in group 1 and 2.4+/-2.3 in group 2. For better
      understanding of the role of intraoperative monitoring, we investigated the
      outcome of patients with acoustic neurinomas who underwent surgery over the
      following 6 months postoperatively. At that time, function improved by 4.1+/-3.2
      (group 1) and 2.0+/-2.3 (group 2). We could show that intraoperative monitoring
      of the facial nerve was a significant factor for better postoperative function in
      patients undergoing microsurgical excision of neurinomas (P=0.001) .

PMID- 15257438
TI  - [Neurocutaneous angiomatosis. Manifestation with cystic tumors].
AB  - A 54-year-old woman developed epilepsy and gait disorder. The initial CCT showed
      multiple intracerebral cysts. Histologically these turned out to be cavities from
      repetitive bleedings out of abnormal vessels in the border region. Regular
      observation during 7 years showed spontaneous episodes of regression and
      progression of the cysts. In addition, multiple hemangiomas of the skin were
      found. The case presented here represents an unusual manifestation of
      neurocutaneous angiomatosis.

PMID- 15257439
TI  - [Mrt-based morphometry. A current assessment].
AB  - Morphometry offers new approaches for in vivo characterization of many neurologic
      and psychiatric pathologies. A survey of recent publications only hints at the
      attractiveness of magnetic resonance-based morphometry: published findings are
      heterogeneous, partly contradictory, and not always plausible in terms of known
      neuropathologic correlates. Hence, the sensitivity of the applied methods should
      be questioned. Three parameters affect the variance in morphometric findings: (1)
      knowledge about normal morphologic variability, (2) confounding physiologic
      parameters, and (3) methodologic misuse. Sound knowledge about the morphologic
      variability of the normal brain is vital for the assessment of volumetric
      findings. Large morphologic variability may also interfere with the precision of
      morphometric methods. The multitude of possible confounding physiologic
      parameters raises the necessity of precise subject control. Magnetic resonance
      scanning artefacts require rigid protocols, and application of the rather complex
      and sensitive methods demands profound insight into the techniques.

PMID- 15257440
TI  - Flux to acetate and lactate excretions in industrial fermentations: physiological
      and biochemical implications.
AB  - The efficiency of carbon conversion to biomass and desirable end products in
      industrial fermentations is diminished by the diversion of carbon to acetate and
      lactate excretions. In this study, the use of prototrophic and mutant strains of
      Escherichia coli, as well as enzyme active site directed inhibitors, revealed
      that flux to acetate excretion is physiologically advantageous to the organism as
      it facilitates a faster growth rate (mu) and permits growth to high cell
      densities. Moreover, the abolition of flux to acetate excretion was balanced by
      the excretion of lactate as well as 2-oxoglutarate, isocitrate and citrate,
      suggesting a 'bottle-neck' effect at the level of 2-oxoglutarate in the Krebs
      cycle. It is proposed that the acetate excreting enzymes, phosphotransacetylase
      and acetate kinase, constitute an anaplerotic loop or by-pass, the primary
      function of which is to replenish the Krebs cycle with reduced CoA, thus
      relieving the bottle-neck effect at the level of 2-oxoglutarate dehydrogenase.
      Furthermore, flux to lactate excretion plays a central role in regenerating
      proton gradient and maintaining the redox balance within the cell. The long-held
      view that flux to acetate and lactate excretions is merely a function of an 'over
      flow' in central metabolism should, therefore, be re-evaluated.

PMID- 15257441
TI  - The erythromycin biosynthetic gene cluster of Aeromicrobium erythreum.
AB  - The erythromycin-biosynthetic (ery) gene cluster of Aeromicrobium erythreum was
      cloned and characterized. The 55.4-kb cluster contains 25 ery genes. Homologues
      were found for each gene in the previously characterized ery gene cluster from
      Saccharopolyspora erythraea. In addition, four new predicted ery genes were
      identified. Two of the new predicted genes, coding for a phosphopantetheinyl
      transferase (eryP) and a type II thioesterase (eryTII), were internal to the ery
      cluster. The other two new genes, coding for a thymidine 5'-diphosphate-glucose
      synthase (eryDI) and a MarR-family transcriptional repressor (ery-ORF25), were
      found at the two ends of the ery cluster. A knockout in eryDI showed it to be
      essential for erythromycin biosynthesis. The gene order of the two ery clusters
      was conserved within a core region of 15 contiguous genes, with the exception of
      IS1136 which was not found in the A. erythreum cluster. Beyond the core region,
      gene shuffling had occurred between the two sides of the cluster. The flanking
      regions of the two ery clusters were not alike in the type of genes found.

PMID- 15257442
TI  - Optimization of cell density and dilution rate in Pichia pastoris continuous
      fermentations for production of recombinant proteins.
AB  - This paper provides an approach for optimizing the cell density (Xc) and dilution
      rate (D) in a chemostat for a Pichia pastoris continuous fermentation for the
      extracellular production of a recombinant protein, interferon tau (INF-tau). The
      objective was to maximize the volumetric productivity (Q, mg INF-tau l(-1) h(
      1)), which was accomplished using response surface methodology (RSM) to model the
      response of Q as a function of Xc and D within the ranges 150< or = Xc < or =450
      g cells (wet weight) l(-1) and 0.1 microm< or = D< or =0.9 microm (microm=0.0678
      h(-1), the maximum specific growth rate obtained from a fed-batch phase
      controlled with a methanol sensor). The methanol and medium feed rates that
      resulted in the desired Xc and D were determined based on the mass balance. From
      the RSM model, the optimal Xc and D were 328.9 g l(-1) and 0.0333 h(-1) for a
      maximum Q of 2.73 mg l(-1) h(-1). The model of specific production rate (rho, mg
      INF-tau g(-1) cells h(-1)) was also established and showed the optimal Xc 287.7 g
      l(-1) and D=0.0361 h(-1) for the maximum rho (predicted to be 8.92 x 10(-3) mg(
      1) g(-1) h(-1)). The methanol specific consumption rate (nu, g methanol g(-1)
      cells h(-1)) was calculated and shown to be independent of the cell density. The
      relationship between nu and mu (specific growth rate) was the same as that
      discovered from fed-batch fermentations of the same strain. The approach
      developed in this study is expected to be applicable to the optimization of
      continuous fermentations by other microorganisms.

PMID- 15257443
TI  - Inhibition of yeast by lactic acid bacteria in continuous culture: nutrient
      depletion and/or acid toxicity?
AB  - Lactic acid was added to batch very high gravity (VHG) fermentations and to
      continuous VHG fermentations equilibrated to steady state with Saccharomyces
      cerevisiae. A 53% reduction in colony-forming units (CFU) ml(-1) of S. cerevisiae
      was observed in continuous fermentation at an undissociated lactic acid
      concentration of 3.44% w/v; and greater than 99.9% reduction was evident at 5.35%
      w/v lactic acid. The differences in yeast cell number in these fermentations were
      not due to pH, since batch fermentations over a pH range of 2.5-5.0 did not lead
      to changes in growth rate. Similar fermentations performed in batch showed that
      growth inhibition with added lactic acid was nearly identical. This indicates
      that the apparent high resistance of S. cerevisiae to lactic acid in continuous
      VHG fermentations is not a function of culture mode. Although the total amount of
      ethanol decreased from 48.7 g l(-1) to 14.5 g l(-1) when 4.74% w/v undissociated
      lactic acid was added, the specific ethanol productivity increased ca. 3.2-fold
      (from 7.42 x 10(-7) g to 24.0 x 10(-7) g ethanol CFU(-1) h(-1)), which indicated
      that lactic acid stress improved the ethanol production of each surviving cell.
      In multistage continuous fermentations, lactic acid was not responsible for the
      83% (CFU ml(-1)) reduction in viable S. cerevisiae yeasts when Lactobacillus
      paracasei was introduced to the system at a controlled pH of 6.0. The competition
      for trace nutrients in those fermentations and not lactic acid produced by L.
      paracasei likely caused the yeast inhibition.

PMID- 15257444
TI  - Incidence and etiological agents of bacterial meningitis among children <5 years
      of age in two districts of Romania.
AB  - To expand upon the limited comprehensive population-based data for childhood
      bacterial meningitis in Eastern Europe, the present study was conducted in the
      Iasi and Constanta districts of Romania. From March 2000 through March 2002,
      children <5 years of age hospitalized for bacterial meningitis were enrolled in a
      prospective surveillance study. A total of 56 cases of bacterial meningitis were
      identified, including 37 due to Neisseria meningitidis (22 per 100,000 per year),
      13 due to Haemophilus influenzae type b (7.6 per 100,000 per year), and six due
      to Streptococcus pneumoniae (3.5 per 100,000 per year). Of the 31 meningococcal
      isolates that were serotyped, 12 were serogroup A, eight were serogroup B, and 11
      were serogroup C. Among all cases of bacterial meningitis, 25 occurred in
      children <1 year of age, including those due to meningococci (n=14), H.
      influenzae type b (n=7), pneumococci (n=3), and Klebsiella pneumoniae (n=1). In
      Romania the incidence of H. influenzae type b meningitis is similar to that found
      in other areas of Southern and Eastern Europe during the pre-vaccination era, and
      the incidence of meningococcal meningitis is one of the highest yet found in
      Europe. An unexpectedly high proportion of these meningococcal meningitis cases
      is due to serogroup A. Disease burden could be substantially reduced through the
      introduction of H. influenzae type b conjugate vaccine and, when available,
      meningococcal conjugate vaccine protective against serogroups A, B and C.

PMID- 15257446
TI  - Case of Lemierre's syndrome presenting with thyroid abscess.
AB  - Lemierre's syndrome is an uncommon condition characterized by post-anginal
      septicemia due to anaerobes. Reported here is a case of Lemierre's syndrome
      presenting with thyroid and liver abscesses. At presentation, the 70-year-old
      female patient complained of fever, jaundice and neck pain. Computed tomography
      (CT) and ultrasound confirmed the presence of a left-sided internal jugular vein
      thrombosis as well as abscesses in the left thyroid lobe and the right lobe of
      the liver with pleural effusion. The thyroid abscess was treated with a left
      lobectomy.

PMID- 15257445
TI  - Mycobacterium malmoense lymphadenitis in Spain: first two cases in
      immunocompetent patients.
AB  - Reported here are two cases of Mycobacterium malmoense lymphadenitis that
      occurred in two immunocompetent children in Spain. To the best of our knowledge,
      these are the first documented cases of extrapulmonary infection by M. malmoense
      in Spain. This report serves to draw attention to this emerging nontuberculous
      mycobacterium that is gaining increasing recognition as a pulmonary and
      extrapulmonary pathogen in different countries.

PMID- 15257447
TI  - Technical consideration for subxiphoidal incisional hernia repair.
AB  - BACKGROUND: The main principle of incisional hernia repair with mesh augmentation
      is a wide overlap of at least 5 cm in all directions. This is complicated when
      cartilaginous or osseous structures border the fascial defect, most notably at
      the xiphoid after sternotomy or in large proximal incisional hernias. METHOD: We
      performed an anatomic investigation of this "problematic" area with its different
      structures and layers that form the retroxiphoidal space. RESULTS AND CONCLUSION:
      The posterior lamina of the rectus sheath inserts on the posterior side of the
      xiphoid. This lamina inhibits a sufficient mesh placement. By sharp dissection
      dorsal the xiphoid process, the posterior lamina of the rectus sheath can be
      detached. This way the retroxiphoidal space can be opened. Further development of
      this space can be made by blunt dissection. In some cases, with retroxiphoidal
      scar formation after sternotomy, a sharp dissection might be necessary. This
      enables a combined retromuscular-retroxiphoid mesh augmentation repair with a
      sufficient underlay of at least 5 cm, according to the principles of sublay
      technique.

PMID- 15257448
TI  - Hernia surgery in the South American woodlands: a surgical adventure in
      Argentina.
AB  - BACKGROUND: Because of the socioeconomic conditions existing today in Argentina,
      I decided to operate on hernias and incisional hernias among the poorest
      population in their living environment. METHODS: To achieve this, I organized a
      group of 19 people, including resident surgeons and technicians, transferring
      everything in order to set up three surgical rooms in an old house, in the worst
      surgical environment, in the middle of the woodlands in the northeast tropical
      part of our country. It was like war-trench surgery but in peacetime. We
      successfully operated on 83 cases with different techniques in 4 days, in a trip
      that lasted a week. RESULTS: After 18 months, there is not even one complication
      or recurrence. CONCLUSIONS: Because of this experience, I must remark that the
      patients' immunity-cicatricial condition is essential to success.

PMID- 15257449
TI  - Congress report of Orlando meeting.

PMID- 15257450
TI  - Distribution of different mycorrhizal classes on Mount Koma, northern Japan.
AB  - To investigate the role of mycorrhizae in nutrient-poor primary successional
      volcanic ecosystems, we surveyed mycorrhizal frequencies on the volcano Mount
      Koma (42 degrees 04'N, 140 degrees 42'E, 1,140 m elevation) in northern Japan.
      After the 1929 eruptions, plant community development started at the base of the
      volcano. Ammonia and nitrate levels, along with plant cover, decreased with
      increasing elevation, whereas phosphorus did not. In total, 305 individuals of 56
      seed plant species were investigated in three elevational zones (550-600 m, 650
      700 m, and 750-800 m). Five mycorrhizal classes were classified based on
      morphological traits: ecto- (ECM), arbuscular (AM), arbutoid, ericoid, and orchid
      mycorrhiza. All plant species were mycorrhizal to at least some extent, with most
      widespread tree species being heavily ectomycorrhizal. In addition, of 16 tree
      species collected in all three zones, 6 differed in the frequencies of ECM on
      roots between elevational zones, and 3 of these 6 species increased in frequency
      with increasing elevation. These results suggest that ECM colonization in some
      tree species is related to establishment in nutrient-poor habitats. All species
      of Ericaceae and Pyrolaceae had ericoid mycorrhizae, and an Orchidaceae species
      had orchid mycorrhizae. Herbaceous species, except for the low mycorrhizal
      frequency of Carex oxyandra and two Polygonaceae species, and ericoid and orchid
      mycorrhizal species, were generally AM. Of herbaceous species, Anaphalis
      margaritacea var. angustior increased AM frequency and decreased ECM frequency
      with increasing elevation, and Hieracium umbellatum increased ECM frequency. In
      total, the establishment of herbaceous species was not sufficiently explained by
      AM colonization on roots. Tree individuals developed 2-3 classes of mycorrhizae
      more than herbs at each elevational zone. We conclude that the symbiosis between
      seed plants and mycorrhizae, ECM in particular, greatly influences plant
      community structures on Mount Koma. Not only a single mycorrhizal class, but
      combinations of mycorrhizal classes should be studied to clarify effects on plant
      community dynamics.

PMID- 15257451
TI  - Cloud cover and horizontal plane eye damaging solar UV exposures.
AB  - The spectral UV and the cloud cover were measured at intervals of 5 min with an
      integrated cloud and spectral UV measurement system at a sub-tropical Southern
      Hemisphere site for a 6-month period and solar zenith angle (SZA) range of 4.7
      degrees to approximately 80 degrees . The solar UV spectra were recorded between
      280 nm and 400 nm in 0.5 nm increments and weighted with the action spectra for
      photokeratitis and cataracts in order to investigate the effect of cloud cover on
      the horizontal plane biologically damaging UV irradiances for cataracts
      (UVBE(cat)) and photokeratitis (UVBE(pker)). Eighty five percent of the recorded
      spectra produced a measured irradiance to a cloud free irradiance ratio of 0.6
      and higher while 76% produced a ratio of 0.8 and higher. Empirical non-linear
      expressions as a function of SZA have been developed for all sky conditions to
      allow the evaluation of the biologically damaging UV irradiances for
      photokeratitis and cataracts from a knowledge of the unweighted UV irradiances.

PMID- 15257452
TI  - Meteorological factors and the onset of hypertensive intracerebral hemorrhage.
AB  - There have been numerous studies of the relationship between intracerebral
      hemorrhage (ICH) and meteorological conditions, but their conclusions have been
      inconsistent. Poor discrimination of ICH subtypes (primary or secondary) may have
      obscured the conclusions. Although most studies have analyzed seasonal or monthly
      variation, daily meteorological data are more appropriate for determining whether
      weather conditions play a role in triggering the onset of ICH. No studies have
      examined the activity and location of patients at the time of onset. The aim of
      this study was to evaluate the relationship between the occurrence of
      hypertensive ICH and daily meteorological parameters, in addition to examining
      the effect of the location and activity of the patient at the time of onset. We
      analyzed 138 patients with severe hypertensive ICH in a hospital-based
      population. We assessed whether daily meteorological parameters for the days on
      which ICH occurred differed from the days without ICH onset. Days on which
      hypertensive ICH occurred had a significantly lower minimum temperature and a
      decreased minimum temperature from that of the previous day ( P=0.042 [corrected]
      and 0.012 [corrected] respectively). There were no significant differences among
      subgroups of patients categorized according to their location and activity at the
      time of onset for any of the meteorological parameters.

PMID- 15257453
TI  - The association between transforming growth factor-beta gene promoter C-509T
      polymorphism and Chinese children with Henoch-Schonlein purpura.
AB  - Many cytokines, including transforming growth factor-beta (TGF-beta) and tumor
      necrosis factor-alpha (TNF-alpha), are involved in the inflammatory process of
      Henoch-Schonlein purpura (HSP). The objective of this study was to investigate
      whether TGF-beta C-509T and TNF-alpha G-308A polymorphisms are associated with
      childhood HSP. The loci of interest were amplified from genomic DNA using
      specific primers and polymerase chain reaction, and these two polymorphisms were
      compared between Chinese children with HSP and healthy controls. The disease
      severities evaluated and expressed as symptom score of patients with different
      genotypes were also compared. The TGF-beta -509 TT genotype was more common in
      children with HSP than controls (31% vs. 8%, P =0.03, odds ratio=4.95). The
      allelic frequencies of TGF-beta -509, genotypic and allelic frequencies of TNF
      alpha -308 were not significantly different. Patients with the TT genotype had
      more severe clinical presentations than non-TT (TC+CC) patients (4.1+/-0.42 vs.
      2.7+/-0.31, P =0.018). These results suggest that the TT genotype of the C-509T
      polymorphism of the TGF-beta gene might be related to the susceptibility of
      Chinese children to HSP and to the severity of this disease.

PMID- 15257454
TI  - Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus
      nephritis. How long? How much?
AB  - The gold standard for inducing remission in systemic necrotizing vasculitis (SNV)
      and severe lupus nephritis is (and remains) the combination of cyclophosphamide
      and glucocorticoids. Long-term treatment with cyclophosphamide is limited because
      of toxicity. Recent prospective studies in antineutrophil cytoplasmic antibody
      (ANCA)-associated SNV revealed that after achievement of clinical remission
      (usually within 3-4 months after starting cyclophosphamide) cyclophosphamide can
      be replaced by azathioprine with no increase in relapse rates if treatment is
      continued for at least 1 year. Methotrexate is inferior to cyclophosphamide
      because of increased relapse rates-particularly in those with renal involvement
      during follow-up. An ongoing study comparing mycophenolate mofetil (MMF) with
      azathioprine will clarify whether MMF is as successful as azathioprine or even
      better. The concomitant use of tumor necrosis factor (TNF)-alpha blockers
      increases the efficacy of immunosuppression. TNF-alpha blockers may be added if
      SNV is refractory to standard immunosuppressive therapy. However, with this
      addition to therapy, systemic infections are more frequent. In patients with
      severe lupus nephritis (WHO IV) the efficacy of combined i.v. therapy with
      cyclophosphamide and glucocorticoids was shown by NIH trials. This NIH regimen
      competes with the EURO-Lupus nephritis schedule with a lower dose of i.v.
      cyclophosphamide followed by maintenance therapy with azathioprine. Long-term
      follow-up is, however, still lacking in the EURO-Lupus trial. Ongoing prospective
      studies will reveal whether cyclophosphamide may be substituted by MMF from the
      very beginning or whether MMF is superior to azathioprine during maintenance
      therapy of lupus nephritis.

PMID- 15257455
TI  - To what extent does the understanding of pharmacokinetics of mycophenolate
      mofetil influence its prescription.
AB  - Within a short period, we have witnessed a dramatic increase in the use of
      mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug
      often replacing azathioprine in combination with calcineurin inhibitor therapy.
      When the drug was introduced, the manufacturer considered therapeutic drug
      monitoring (TDM) unnecessary. However, TDM studies revealed substantial inter-
      and intra-individual variability and drug interactions. There is a substantial
      drug interaction between MMF and cyclosporine, and lower doses are required in
      combination with tacrolimus (~500-800 mg/m(2) per day) than with cyclosporine
      (~1,200 mg/m(2) per day). Patients with autoimmune disease require an
      intermediate dose when receiving no concomitant calcineurin inhibitor (~900
      mg/m(2) per day). It has been possible to detect drug interactions and to
      minimize adverse events only with TDM. This is especially important with
      increasing use of combination therapies. Pharmacodynamic monitoring (measuring
      the biological response to a drug) coupled with pharmacokinetics allow
      optimization of drug dosing, with maximum efficacy and minimal toxicity. More
      work is required to establish specific target ranges with the various drug
      combinations--especially for the pediatric population.

PMID- 15257456
TI  - CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and
      Jewish kindreds.
AB  - Microphthalmia/anophthalmia is a clinically heterogeneous disorder of eye
      formation, ranging from small size of a single eye to complete bilateral absence
      of ocular tissues. The genetic defect underlying isolated autosomal recessive
      microphthalmia/anophthalmia is yet unclear. We studied four families (two of Arab
      origin, one of Bedouin origin, and one of Persian-Jewish origin) with autosomal
      recessive microphthalmia/anophthalmia and no associated eye anomalies, and one
      Syrian-Jewish family with associated colobomas. Assuming a founder effect in each
      of the families, we performed homozygosity mapping using polymorphic markers
      adjacent to human homologues of genes known to be associated with eye absence in
      various species, namely EYA1, EYA2, EYA3, SIX4, SIX6, PAX6 and CHX10. No
      association was found with EYA1, EYA2, EYA3, SIX6 or PAX6. In two families,
      linkage analysis was consistent with possible association with SIX4, but no
      mutations were found in the coding region of the gene or its flanking intron
      sequences. In three of the five families, linkage analysis followed by sequencing
      demonstrated that affected individuals in each family were homozygous for a
      different CHX10 aberration: a mutation in the CVC domain and a deletion of the
      homeobox domain were found in two Arab families, and a mutation in the donor
      acceptor site in the first intron in the Syrian-Jewish family. There was
      phenotypic variation between families having different mutations, but no
      significant phenotypic variation within each family. It has been previously shown
      that mutations in a particular nucleotide in CHX10 are associated with an
      autosomal recessive syndrome of microphthalmia/anophthalmia with iris colobomas
      and cataracts in two families. We now show that different mutations in other
      domains of the same gene underlie isolated microphthalmia/anophthalmia.

PMID- 15257457
TI  - The genes and enzymes for the catabolism of galactitol, D-tagatose, and related
      carbohydrates in Klebsiella oxytoca M5a1 and other enteric bacteria display
      convergent evolution.
AB  - Enteric bacteria (Enteriobacteriaceae) carry on their single chromosome about
      4000 genes that all strains have in common (referred to here as "obligatory
      genes"), and up to 1300 "facultative" genes that vary from strain to strain and
      from species to species. In closely related species, obligatory and facultative
      genes are orthologous genes that are found at similar loci. We have analyzed a
      set of facultative genes involved in the degradation of the carbohydrates
      galactitol, D-tagatose, D-galactosamine and N-acetyl-galactosamine in various
      pathogenic and non-pathogenic strains of these bacteria. The four carbohydrates
      are transported into the cell by phosphotransferase (PTS) uptake systems, and are
      metabolized by closely related or even identical catabolic enzymes via pathways
      that share several intermediates. In about 60% of Escherichia coli strains the
      genes for galactitol degradation map to a gat operon at 46.8 min. In strains of
      Salmonella enterica, Klebsiella pneumoniae and K. oxytoca, the corresponding gat
      genes, although orthologous to their E. coli counterparts, are found at 70.7 min,
      clustered in a regulon together with three tag genes for the degradation of D
      tagatose, an isomer of D-fructose. In contrast, in all the E. coli strains
      tested, this chromosomal site was found to be occupied by an aga/kba gene cluster
      for the degradation of D-galactosamine and N-acetyl-galactosamine. The aga/kba
      and the tag genes were paralogous either to the gat cluster or to the fru genes
      for degradation of D-fructose. Finally, in more then 90% of strains of both
      Klebsiella species, and in about 5% of the E. coli strains, two operons were
      found at 46.8 min that comprise paralogous genes for catabolism of the isomers D
      arabinitol (genes atl or dal) and ribitol (genes rtl or rbt). In these strains
      gat genes were invariably absent from this location, and they were totally absent
      in S. enterica. These results strongly indicate that these various gene clusters
      and metabolic pathways have been subject to convergent evolution among the
      Enterobacteriaceae. This apparently involved recent horizontal gene transfer and
      recombination events, as indicated by major chromosomal rearrangements found in
      their immediate vicinity.

PMID- 15257458
TI  - Analysis of TBX18 expression in chick embryos.
AB  - T-box genes encode transcription factors that control the development of diverse
      tissues and organs in vertebrate embryos. Here, we report the expression of the
      TBX18 gene during chick development. TBX18 expression is found in anterior halves
      of prospective and definitive somites as well as in the unsegmented cranial
      region of the paraxial mesoderm. Expression levels are high in the presomitic
      mesoderm but decrease in newly formed somites. This is in contrast to the mouse
      where uniform expression has been reported in the paraxial mesoderm. TBX18
      expression is also prominent in the proepicardial serosa and in the epicardium of
      the heart. Other sites of expression include the genital ridge and the developing
      limb buds.

PMID- 15257459
TI  - WITHDRAWN: A novel calmodulin-interacting protein (CUGT1) is rapidly induced by
      stress signals in Arabidopsis.
AB  - The manuscript has been withdrawn on request of the authors and will not be
      published in that version in the print edition of Planta.

PMID- 15257460
TI  - Hyperglycemia-induced oxidative stress in diabetic complications.
AB  - Reactive oxygen species are increased by hyperglycemia. Hyperglycemia, which
      occurs during diabetes (both type 1 and type 2) and, to a lesser extent, during
      insulin resistance, causes oxidative stress. Free fatty acids, which may be
      elevated during inadequate glycemic control, may also be contributory. In this
      review, we will discuss the role of oxidative stress in diabetic complications.
      Oxidative stress may be important in diabetes, not just because of its role in
      the development of complications, but because persistent hyperglycemia, secondary
      to insulin resistance, may induce oxidative stress and contribute to beta cell
      destruction in type 2 diabetes. The focus of this review will be on the role of
      oxidative stress in the etiology of diabetic complications.

PMID- 15257461
TI  - Polypoidal choroidal vasculopathy in elderly Chinese patients.
AB  - PURPOSE: To investigate the frequency and clinical features of polypoidal
      choroidal vasculopathy (PCV) in a consecutive series of elderly Chinese patients.
      METHODS: A restrospective analysis of 166 consecutive patients 50 years or older
      with diagnosis of exudative age-related macular degeneration (AMD) was conducted.
      Color fundus photographs were taken and fluorescein and indocyanine green (ICG)
      angiography were performed in all patients. RESULTS: Of the 166 patients, 37
      patients (22.3%) initially suspected of having exudative AMD were ultimately
      diagnosed as having PCV. Twenty-seven men (73.0%) were affected, 32 patients
      (86.5%) were unilaterally involved. Of 42 eyes with PCV, 27 eyes (64.3%)
      demonstrated polypoidal dilations with branching vascular network, and the other
      15 eyes (35.7%) showed scattered polypoidal dilations without identifiable
      continuous branching vascular network on ICG angiography. The predominant
      location for these lesions was at the macular region in 26 eyes (61.9%), the
      temporal vascular arcade in 9 eyes (21.4%), the peripapillary area in 6 eyes
      (14.3%), and the midperiphery in 1 eye (2.4%). CONCLUSIONS: PCV is a common
      disease in elderly Chinese patients. In our study group PCV mainly affected men
      and was mostly unilateral. Most of the lesions were located in the macular region
      and temporal vascular arcade.

PMID- 15257462
TI  - Retinal thickness at the posterior pole in glaucoma and ocular hypertension.
AB  - PURPOSE: Ganglion cells with nerve fibre layer contribute a substantial fraction
      to the retinal thickness (RT). In contrast to the analysis of papillary and
      peripapillary area, which have shown large variability in normal eyes, the
      variation of retinal cell density in the perifoveal region is reported to be less
      than 10%. By measuring RT at the posterior pole we wanted to detect retinal
      changes due to glaucoma and determine their correspondence with visual field (VF)
      changes. METHODS: The Retinal Thickness Analyzer (RTA) was used to obtain RT maps
      in 21 normal eyes, 20 eyes with ocular hypertension and 22 eyes with glaucoma. A
      green laser slit (540 nm) of the RTA was focused on the retina at an angle and
      its intersection with the retina was imaged. The distance between the reflections
      from the vitreo-retinal and retina-retinal pigment interface is directly
      proportional to the RT. Five locations covering the central 20 degrees were
      scanned, generating 10 optical cross sections that were transformed into colour
      coded RTA maps. Numerical data were presented for the perifoveal and posterior
      pole region. RESULTS: In glaucomatous eyes significant localised thinning of the
      retina was present, identified as the increased number of clusters including at
      least four points that are 2 standard deviations below normal. The minimum
      retinal thickness was decreased in glaucoma eyes and the perifoveal temporal
      modulation and perifoveal temporal/nasal asymmetry--indicators of greater RT loss
      in the temporal and the nasal quadrant, respectively--were higher in eyes with
      glaucoma, but with overlapping global indices between the groups. In 16 of 22
      eyes with glaucoma there was good agreement of RT changes with VF defects. In two
      eyes with typical glaucomatous damage at the optic disc but without VF defects
      localised changes of RT were detected. CONCLUSIONS: The RTA enables objective
      noninvasive evaluation of the posterior pole and could become helpful in
      diagnosis of glaucoma before the onset of functional damage. However, at present
      its clinical usefulness is limited by overlapping values of retinal thickness
      between normal and glaucomatous populations.

PMID- 15257464
TI  - Artificial recombination in forensic mtDNA population databases.
AB  - Artificial recombination of two or more mitochondrial DNA fragments from
      different samples would constitute a serious cause of error in forensic DNA
      typing, and yet one can demonstrate that such events have happened in the
      preparation of several published mtDNA databases. Focussed database searches,
      phylogenetic analysis, and network representations can highlight mosaic patterns
      and thus pinpoint sample mix-up. Therefore, we suggest that this approach should
      be applied to data prior to publication in order to uncover such errors in time.

PMID- 15257465
TI  - Diverse patterns of the tandem repeats organization in rye chromosomes.
AB  - Although the monomer size, nucleotide sequence, abundance and species
      distribution of tandemly organized DNA families are well characterized, little is
      known about the internal structure of tandem arrays, including total arrays size
      and the pattern of monomers distribution. Using our rye specific probes, pSc200
      and pSc250, we addressed these issues for telomere associated rye heterochromatin
      where these families are very abundant. Fluorescence in situ hybridization (FISH)
      on meiotic chromosomes revealed a specific mosaic arrangement of domains for each
      chromosome arm where either pSc200 or pSc250 predominates without any obvious
      tendency in order and size of domains. DNA of rye-wheat monosomic additions
      studied by pulse field gel electrophoresis produced a unique overall blot
      hybridization display for each of the rye chromosomes. The FISH signals on DNA
      fibres showed multiple monomer arrangement patterns of both repetitive families
      as well as of the Arabidopsis-type telomere repeat. The majority of the arrays
      consisted of the monomers of both families in different patterns separated by
      spacers. The primary structure of some spacer sequences revealed scrambled
      regions of similarity to various known repetitive elements. This level of
      complexity in the long-range organization of tandem arrays has not been
      previously reported for any plant species. The various patterns of internal
      structure of the tandem arrays are likely to have resulted from evolutionary
      interplay, array homogenization and the generation of heterogeneity mediated by
      double-strand breaks and associated repair mechanisms.

PMID- 15257467
TI  - [Inhalative antimicrobial treatment of bronchiectasis].

PMID- 15257466
TI  - Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle
      progression and leads to apoptosis.
AB  - Among proteins involved in homologous recombination, Rad51 is an essential enzyme
      in DNA repair and recombination. However, little is known about its role in cell
      cycle regulation and apoptosis. To examine the function of Drosophila Rad51
      (DmRad51) in cell cycle regulation and apoptosis, DmRad51 protein was
      overexpressed using a heat shock-inducible promoter or the UAS-GAL4 binary
      expression system. We observed that ubiquitous expression of DmRad51 protein in
      flies carrying hsp26- Rad51 or UAS- Rad51 transgenes was lethal. Induction of
      DmRad51--more specifically in eye or wing imaginal discs--caused tissue-specific
      cell death in the domains of DmRad51 expression. Cell death was due to apoptosis,
      as shown by staining with the TdT-mediated dUTP nick-end labeling assay.
      Immunocytochemistry revealed that cells expressing DmRad51 colocalized with
      apoptotic cells. In addition, the phenotypes caused by the overexpression of
      DmRad51 were similar to those caused by ectopic expression of Reaper, a
      proapoptotic protein, and were partially suppressed by the coexpression of p35,
      an antiapoptotic protein. Using an antiphosphohistone H3 antibody, we also
      observed that the overexpression of DmRad51 protein disrupted normal cell cycle
      progression in eye imaginal discs. Taken together, these results show that
      ectopically expressed DmRad51 disrupts cell cycle regulation and induces
      apoptosis.

PMID- 15257468
TI  - [pH-Testing - experience in clinical practice in a pulmonary division].
AB  - The association between lung disease and gastroesophageal reflux has been
      discussed for a long time. Aim of this retrospective study was to clarify
      evidence and acceptance of pH-testing in a pulmonary division. METHOD: pH-testing
      data at the Krankenhaus Grosshansdorf from January 2000 till March 2004 was
      evaluated and clinical and pulmonary functional data assessed. RESULTS: A total
      of 186 patients (113 female, 73 male) received a pH-monitoring. The most
      important indication was chronic cough (94.6 %). Of 165 evaluable subjects, 63
      patients had asthma, 54 patients chronic cough, 18 COPD and 30 patients various
      diseases (fibrosis, pneumonia, tuberculosis, bronchiectasis a. s. o.). 51 % of
      patients showed a pathological gastroesophageal reflux (median DeMeester score
      22.3). Neither BMI nor patient subgroups correlated significantly with DeMeester
      score. In 62 % of asthmatics, 57 % of patients with chronic cough and 33 % of
      COPD patients a pathological reflux was found. In the subgroup with various
      diseases there was pathological reflux detected in 30 %. CONCLUSIONS: pH-testing
      is a reliable and safe method to determine gastroesophageal reflux in pulmonary
      diseases. Pathological reflux is frequently found even without typical symptoms.
      It remains unclear whether there is a causal relationship.

PMID- 15257469
TI  - [Effect of two doses of budesonide on exhaled nitric oxide and urinary EPX
      excretion in asthmatic children].
AB  - The use of objective outcome measures that assess airway inflammation in
      pediatric asthma can provide a good evaluation of asthma severity and treatment
      response. In this double-blind and randomized study the effects of 200 micro g of
      budesonide and 800 micro g of budesonide on markers of inflammation (exhaled
      nitric oxide (eNO), eosinophil protein X (EPX) excretion in urine) and on lung
      function (FEV (1)) were prospectively investigated in 24 ICS-naive children with
      mild persistent to moderate persistent asthma over a period of eight weeks. After
      eight weeks of treatment 200 micro g and 800 micro g of budesonide led to a
      significant decrease (p < 0.025) in eNO [median (90 % interval): 200 micro g: -
      17.2 ppb (- 54.6 to 0.9); 800 micro g: - 13.2 ppb (- 44.6 to - 1.7)]. A
      significant change in urinary EPX excretion was only observed in the high dose
      group [200 micro g: - 10.3 micro g/mmol creatinine (- 116.2 to 50.5), p = 0.9;
      800 micro g: - 49.2 micro g/mmol creatinine (- 231.0 to 48.7), p = 0.02].
      However, a significant difference between the change from baseline after 8 weeks
      of either group was found neither for eNO (p = 0.66) nor for EPX excretion (p =
      0.04). In conclusion, our data demonstrate that 800 micro g budesonide per day
      did not show any advantage in reduction of airway inflammation, measured by eNO
      and urinary EPX excretion, in children with mild persistent to moderate
      persistent asthma.

PMID- 15257470
TI  - [Bronchoscopic resection of an endobronchial hamartochondroma].
AB  - The endobronchial hamartochondroma is a very rare, slowly growing benign tumor.
      We report a case of hamartochondroma conglomerate located in the left main
      bronchus. The resection via rigid endoscopy with ND-YAG laser and forceps was
      successful, and no complications occured. The rigid endoscopy with laser
      application in such case is a safe and effective procedure in endobronchial
      hamartochondroma.

PMID- 15257471
TI  - [Bronchioloalveolar carcinoma of the lung associated with a highly positive pANCA
      titer and clinical signs of microscopic polyangiitis].
AB  - Autoimmune paraneoplastic processes are investigated in detail concerning the
      Lambert-Eaton-Myasthenic-Syndrome for bronchial carcinomas. For the cutaneous
      leukocytoclastic vasculitis as a non-ANCA-associated vasculitis the
      paraneoplastic genesis is described. Litttle is known about ANCA-associated
      vasculitis as a paraneoplastic autoimmune phenomenon. We present the case of a 62
      year old woman referred to our hospital presenting air-space shadows mainly in
      both upper lobes, skin rash with petechial bleeding and a highly positive pANCA
      titer. A bronchioloalveolar carcinoma was diagnosed by surgical biopsy. The
      patient developed renal failure postsurgically and died a few weeks after the
      diagnosis was established. This is the 5 (th) case in literature of the temporal
      concurrence of a bronchial carcinoma and an ANCA-associated vasculitis. So far
      only 24 cases of a solid tumor occuring simultaneously with an ANCA-positive
      vasculitis are reported in literature.

PMID- 15257472
TI  - [Inhaled antibiotic therapy in bronchiectasis?].
AB  - Antimicrobial therapy is an important aspect of disease management for patients
      with bronchiectasis. Delivery of an inhaled antibiotic is an appealing
      alternative to oral or intravenous administration because the antibiotic is
      delivered in high concentrations directly to the site of infection, eliminating
      the need for high systemic concentrations and reducing the risk of systemic
      toxicity. In recent controlled studies these potential benefits have been
      assessed in patients with bronchiectasis who became colonized by P. aeruginosa
      and the results support the use of nebulized antibiotics. In up to one-third of
      patients P. aeruginosa was eradicated from their sputum by inhaled antibiotic
      therapy and up to 62 % of patients showed improved medical condition. The further
      development of new aerosol devices supported by clinical testing will allow
      effective management of patients with bronchiectasis by an inhalation therapy
      that minimizes time constraints and drug loss which may improve health status and
      quality of life.

PMID- 15257473
TI  - [Cardiovascular diseases and sleep-disordered breathing].
AB  - About 1.9 % of the population suffer from an obstructive sleep apnea syndrome
      (OSAS). At the age of between 30 and 60 years it occurs in 3 %. Patients with
      OSAS develop more frequently such disorders as arteriosclerosis, cardiac
      arrhythmias and arterial hypertension. A host of pathophysiological changes can
      be diagnosed. The elevated sympathic activity, recurrent hypoxemias, stress,
      disturbances in the microvascular milieu, endothelial dysfunction, elevated
      oxidative capacity as well as a reduced vascular reagibility are deemed to be
      factors connected to arteriosclerosis. Different biochemical markers, which are
      seen as risk factors or as markers of cardiovascular diseases, are altered in
      patients with OSAS (high-sensitive CRP, Interleukin(IL)-6, IL-8, IL-10, TNF
      alpha, VGEF, ICAM-1, VCAM-1 and L-Selectin). Patients with OSAS exhibit signs of
      an impaired insulin sensitivity. Disturbances in microcirculation are also
      evident. Patients with OSAS have, compared to patients without sleep apnea,
      elevated blood pressure measurements, even given other common risk factors. The
      incidence of coronary heart diseases is increased in patients with OSAS.
      Morbidity and mortality, especially of arteriosclerotic diseases are elevated.
      Many of the aforementioned disturbances can be improved by a CPAP-therapy.

PMID- 15257474
TI  - [Non-invasive methods for monitoring airway inflammation: a comparison of
      expenditures, gain and clinical value].
AB  - Among the noninvasive procedures for the assessment of airway inflammation, the
      analysis of spontaneous sputum is currently the only method, the expenses of
      which are covered by health insurance in Germany. It can easily be used for
      semiquantitive cytological analyses by practising pneumologists. Recent data also
      indicate the usefulness of sputum induction, particularly in asthma diagnosis and
      therapy control, and demonstrate its capability of reducing total costs per
      patient. In contrast to sputum analysis, the measurement of exhaled nitric oxide
      (NO) yields a read-out without time delay. NO as associated with eosinophils also
      seems suitable for monitoring airway inflammation. The number of studies
      regarding NO, both its pathophysiological role and clinical use, is far greater
      than that regarding any other marker of exhaled air. Measurements are easy and
      fast, but the costs of analysers are still prohibitive in clinical practice. The
      analysis of other compounds of exhaled air, particularly those of exhaled breath
      condensate (EBC), offers fascinating perspectives, owing to the scope of markers
      that might be measured, and could enable the assessment of multivariate profiles
      that are useful for diagnosis and therapy control. Currently, however, the method
      still faces methodological questions, and data indicating its usefulness and cost
      efficiency in clinical practice are scarce. Compared to NO, the expenses per
      measurement in clinical use are mainly due to the costs per marker detection
      after sampling, as well as storage and transport of samples. The on-site analysis
      of pH in the EBC could be a first step to circumvent this obstacle.

PMID- 15257475
TI  - [Pleura: non-neoplastic disorders].

PMID- 15257476
TI  - [The history of percussion and auscultation].

PMID- 15257477
TI  - Role of women in medicine: a look at the history, the present condition and the
      future status of women in the surgical field, especially neurosurgery.
AB  - We have analyzed the historical background of women's progress in medicine in
      Japan and the role of female neurosurgeons as models for the next generation.
      Female neurosurgeons were asked to complete a questionnaire regarding their
      professional life in detail and the problems they are facing while managing their
      personal life after getting married and having a child. Some feel that there
      remain some constraints at work for being a female, due to their male colleagues
      who are not so understanding in nature. The younger generation is not so keen on
      joining the neurosurgical branch as their life career due to hard work and
      complete dedication demanded by neurosurgery. It is not easy for all to manage a
      neurosurgical career along together with a married life and children. Hence it is
      now time for those successful female neurosurgeons to become role models.
      Government can play an important role in these social reforms by coming up with
      programs to give social security to females and initiate programs for child care
      for married females pursuing such a demanding profession. Certain measures to
      encourage females to take up surgery are providing more time by arranging care
      for babies and families, flexibility in working hours, in addition to having a
      considerate husband and a considerate chief of department and senior staff.
      Departmental policies need to be completely impartial and should promote everyone
      based on their skills and knowledge. Women neurosurgeons need to get together and
      discuss all these issues so that the younger generation will not hesitate to take
      up this profession and become stalwarts of neurosurgery like their male
      counterparts.

PMID- 15257478
TI  - High-resolution laser surface scanning for patient registration in cranial
      computer-assisted surgery.
AB  - OBJECTIVE: Markerless patient registration is a new procedure that may reduce
      logistical efforts and possibly also the radiation load on the patients prior to
      a computer-assisted intervention. Congruent surfaces, such as bone surfaces or
      skin surfaces, represented in a data set and in the surgical site, can be
      overlapped using surface-matching. Previous studies describing this kind of
      markerless registration, however, show inaccuracies of up to 10 mm during
      computer-assisted navigation. Furthermore, these systems use less than 1000
      surface points of the soft tissue surface in order to establish a correlation
      between the patient and the data set. Previous papers did not answer the question
      whether it is this scanning resolution that induces these inaccuracies in
      registration or rather intraoperative skin deformations. STUDY DESIGN: In the
      present study therefore a new navigation system (SSN++) was used which is able to
      register up to 180,000 surface points of the surgical site. SSN++ is an infrared
      navigation system enlarged by a Minolta VI 900 3D volume digitizer. Three
      different kinds of laser scan-resolution were used for data correlation. An
      additional congruence analysis was performed in order to assess the geometry of
      the matched skin surfaces. 22 patients suffering from different cranial diseases
      (tumors, bony malformations, foreign bodies) were prepared for a computer
      assisted intervention. Intraoral titanium-markers, rigidly fixed on the patients
      by a maxillary splint, were placed as targets while the CT data sets were made.
      These targets were - after markerless laser scan registration of the patients -
      supposed to serve for validating the new high-resolution navigation system SSN++.
      RESULTS: The accuracy of markerless laser scan registration depends on the
      intraoperative laser scan's resolution. A high accuracy of the data correlation
      can be achieved if the number of the laser scan cloud points is about the same as
      the number of voxels of the corresponding surface on the CT data set. A reduction
      of the laser scan cloud points to less than 10 % compared to the number of voxels
      of the CT surface, however, leads to a significant loss of accuracy after
      markerless patient registration. CONCLUSION: The markerless laser scan
      registration of the surgical site may achieve the same accuracy as a patient
      registration made by rigidly fixed titanium screws (mean accuracy: 1.2 mm) as
      long as a high-resolution laser scan is being used.

PMID- 15257479
TI  - Vibrography: first experimental results in swine brains.
AB  - OBJECT: The aim of this study was to determine whether vibrography, an ultrasound
      based real-time strain imaging method for registering the elastic properties of
      tissue, is superior to conventional ultrasound imaging techniques for detecting
      low-contrast space-occupying lesions in brain tissue and for delineating the
      boundaries between such lesions and the surrounding tissue. METHODS: As our
      experimental model we used swine brains taken from freshly slaughtered pigs.
      After injecting agarose into these brains at different depths, we compared both
      the conventional ultrasonographic images and the elastographic images of the
      region of interest with the corresponding anatomical brain sections. RESULTS: In
      83.6 % of the experiments, it was possible to detect the polymerized agarose in
      the brain tissue with vibrographic techniques. In 17 experiments agarose lesions
      which were not detectable by ultrasound were visualized via vibrography.
      Furthermore, statistical analysis revealed that elastography is a more precise
      tool than conventional ultrasound for determining lesion size. CONCLUSION: These
      findings indicate that vibrography is a promising real-time imaging method with
      numerous potential applications in the field of neurosurgery. Visualization of
      the elastic properties provides the neurosurgeon with additional data on the
      lesion and the boundary between the lesion and the surrounding tissue.

PMID- 15257480
TI  - Trapped fourth ventricle treated with shunt placement in the fourth ventricle by
      direct visualization with flexible neuroendoscope.
AB  - Shunt placement was the most common procedure used for ventricular dilatation,
      but in many neurosurgical centers it has been substituted by flexible
      neuroendoscope; however, none of them had solved the problem of the trapped and
      dilated fourth ventricle. The combination of the ventricle-peritoneal catheter
      placement in the center of the fourth ventricle by direct visualization with a
      flexible neuroendoscope using a single coronal burr-hole has solved this problem.
      Eleven patients with a trapped fourth ventricle, with previous third
      ventriculostomy and aqueductal plasty, were treated with this procedure; all
      patients were evaluated clinically and with computed tomography 8 to 24 months
      (mean, 18 months) later. Here, we describe the technical procedure.

PMID- 15257481
TI  - A simplified endoscopic third ventriculostomy under local anesthesia.
AB  - The aim of this study is the analysis of our experience with awake endoscopic
      third ventriculostomy (ETVS) in hydrocephalic patients. From September 1994 to
      December 2001, 24 neuroendoscopic procedures were performed under local
      anesthesia. Local infiltration was administered using a bupivacaine and lidocaine
      mixture. Analgesics were titrated to the effect. A free-hand technique with a
      flexible endoscope was adopted in 24 patients with primitive and secondary
      (neoplastic) hydrocephalus. ETVS was performed successfully in all cases. No
      procedure needed to be discontinued due to seizures, bleeding or agitation. Dural
      incision/coagulation and Fogarty dilatation proved to be the most painful
      maneuvers requiring, sometimes, supplemental analgesic administration. No
      intraoperative complications were observed; however, two asymptomatic trajectory
      hematomas were incidentally discovered two and three days after the operation,
      respectively. Awake ETVS is a valuable alternative procedure that can be adopted
      in adult cooperative patients, provided that the procedure is done in an
      essential and fast way with the free-hand technique, by means of a flexible
      endoscope, and with the assistance of an anesthesiologist.

PMID- 15257482
TI  - Why are aneurysms of the posterior inferior cerebellar artery so unique? Clinical
      experience and review of the literature.
AB  - BACKGROUND: Aneurysms of the posterior inferior cerebellar artery (PICA) are rare
      lesions. The anatomical behaviour of the artery itself is complex and
      characterised by a multitude of variations. The same holds true for the aneurysms
      discovered there. Dissecting aneurysms can be found from the PICA origin to the
      distal artery berry. They have a wider range of clinical and radiographical
      presentations and their surgical treatment requires more than one standard
      approach. METHODS: We encountered 14 patients with PICA aneurysms within two
      surgical series of a total of 1345 cerebral aneurysm patients (1 %). In this
      patient group of the last 27 years only 3 of the 14 were distal aneurysms ("true"
      PICA aneurysms) RESULTS: The 14 patients harboured 15 aneurysms (9 right-sided
      and 6 left-sided). The female/male ratio of the patients was 9/5, the mean age
      52.7 years. 13 of them had sustained an SAH. 7/14 patients were hypertensive, in
      10 patients at least one of putative cerebrovascular risk factors was found. From
      the 15 aneurysms treated, 11 were typical berry aneurysms, 4 dissecting
      aneurysms. The aneurysms ranged in size from 5 to 20 mm (mean 9.1). 11 aneurysms
      were located within the anterior medullary segment, 1 in the tonsillomedullary
      and 2 in the telovelomedullary segments. All patients were surgically treated, 10
      in a semi-sitting position via a suboccipital craniotomy, 4 in the prone
      position. 13 aneurysms were clipped, two were treated differently. Two patients
      died due to their bad preoperative clinical status. CONCLUSIONS: The clinical,
      radiographical and surgical approaches to PICA aneurysms still represent a
      challenge.

PMID- 15257483
TI  - Vascular anatomy of the foramen of Vicq d'Azyr: a microsurgical perspective.
AB  - INTRODUCTION: The foramen of Vicq d'Azyr, is a triangular-shaped area located
      rostral to the ventral median fissure of the medulla oblongata. Its importance
      relies on the fact that it is penetrated by small vessels from the
      vertebrobasilar axis that nourish vital pontine nuclei and tracts. We described
      the microvascular anatomy of the perforating vessels of the foramen of Vicq
      d'Azyr (FVA). MATERIALS AND METHODS: The vertebrobasilar junction arteries and
      the perforating arteries of the foramen of Vicq d'Azyr were examined using a
      surgical microscope in 21 formalin-fixed brain stems. RESULTS: The total number
      of perforating branches found was 286 in the 21 brains, an average of 13.6
      perforators per brain, range 7 to 22. They arose as distal branches of 73 main
      trunks, average of 3.5 per brain, range 2 to 5, originating mainly from the
      basilar artery in 41 (56.1 %); the left ventral spinal artery in 12 (16.4 %), and
      the left vertebral artery in 8 (11 %). The average outer diameters of the left
      and right vertebral arteries were 3.2 mm and 2.9 mm, 4.1 mm for the basilar
      artery, and 0.6 mm for the right and left ventral spinal arteries. The branching
      pattern and interesting anatomic variations of the main vessels of the vertebro
      basilar junction are also described. DISCUSSION: The vascular anatomy of the
      infratentorial compartment is highly variable. These variations should be kept in
      mind to avoid pitfalls during vascular or tumor surgery. In contrast, the
      entering locations of perforating vessels remain constant, referring to these
      zones as key areas when planning or doing surgical procedures in this region.

PMID- 15257484
TI  - Histopathologic changes in oculomotor nerve and ciliary ganglion in aneurysmatic
      compression injuries of oculomotor nerve.
AB  - BACKGROUND: Bilateral common carotid artery ligation (BCCAL) increases
      vertebrobasilar blood flow and leads to increased luminal pressure, luminal
      enlargement, wall thinning, convolutions and sometimes aneurysm formation in
      posterior circulation arteries, especially the posterior communicating arteries
      (PcomA). PcomA aneurysms compress the oculomotor nerves. The principal aim of
      this investigation is to examine the histopathologic results of the compressive
      effect of PcomA aneurysms on the oculomotor nerves (OMN) and on ciliary ganglions
      (CG). METHODS: When we observed the effects of BCCAL on the posterior circulation
      arteries of the brain in fifteen ligated rabbits after sacrifice, we noticed
      aneurysm formation on these arteries in three rabbits. These aneurysms developed
      on the PcomAs compressed the oculomotor nerves. These compressed nerves and
      normal oculomotor nerves together with their ciliary ganglions were examined
      histopathologically. RESULTS: A PComA aneurysm developed in three rabbits from 15
      ligated animals and these aneurysms compressed the oculomotor nerves on the same
      side. Partial peripheral necrosis and axonal loss were seen on the compressed
      oculomotor nerves. Concomitantly, cellular loss and necrosis were also observed
      on their ganglions. CONCLUSION: Bilateral common carotid artery ligation may lead
      to PcomAs and these aneurysms could compress the oculomotor nerves. Compression
      injuries of oculomotor nerve may cause cellular injury and necrosis on both
      oculomotor nerves and ciliary ganglions.

PMID- 15257485
TI  - Percutaneous transarticular atlantoaxial screw fixation using a cannulated screw
      system and image guidance.
AB  - In 2000 a cannulated screw stabilization system for posterior cervical
      instrumentation was introduced in our department for use in complex cervical
      fixation procedures. A special feature of the system is the use of thin Kirschner
      wires for drilling the screw paths and then placing the self-drilling, cannulated
      screws securely over the wires. Percutaneous application of C1-C2 transarticular
      screws is possible through tubes. An optional "atlas-claw" provides additional
      stability in cases of C1-C2 stabilization. 17 patients (10 female, 7 male, mean
      age 60 years) with complex cervical disorders and instability of different origin
      were stabilized using the Neon System (Ulrich Co., Ulm, Germany). Pathology
      included atlantoaxial instability based on rheumatoid arthritis (n = 12),
      odontoid fracture (n = 4) and os odontoideum mobile (n = 1). Computed navigation
      (STN 4.0, Zeiss or vector vision spine, brain lab) was used in 14 cases.
      Transarticular C1-C2 screw fixation was performed in 14 cases (4 patients with
      direct C1 massa lateralis screw fixation), craniocervical fixation (C0-C2/C3) was
      done in 3 patients. Percutaneous application of the C1-C2 screws was used in 7
      patients. Atlas claws were applied in 8 patients. There was one medial
      perforation of a C2 pedicle wall and one malposition of the screw in C2 without
      reaching the lateral mass of C1. After a mean follow-up of 9 months there were no
      hardware failures and stable fusion in those cases followed after 12 months or
      more. Clinical results were excellent or good in 14/16 patients. Cannulated
      screws are an effective alternative in complex stabilization procedures of the
      cervical spine. The presented system is technically comfortable and allows safe
      percutaneous screw application as well as inclusion of computed navigation with
      high accuracy.

PMID- 15257486
TI  - Simple anterior orbitotomy.
AB  - OBJECTIVE: Simple anterior orbitotomy is one of the popular surgical procedures
      through the orbital cavity. In this approach no bony orbitotomy is required so
      very satisfactory cosmetic results should be achieved. The authors of this paper
      report on three patients with space-occupying lesions in orbital cavity which
      were operated by anterior orbitotomy techniques without craniotomies. METHODS:
      Three patients with space-occupying lesions in the orbital cavity underwent a
      microsurgical procedure with simple anterior orbitotomy. RESULTS: No bony
      orbitotomy was used in this technique and the cosmetic results were very
      satisfactory. Although the surgical area is very narrow, no neurological deficit
      has appeared after this procedure using microsurgical operative procedures.
      CONCLUSION: Although the orbital cavity is very narrow, multiple neurological
      important structures occur in this area. Traction of the ocular bulb and optic
      nerve can be harmful for the patient. Therefore, many the surgeons prefer the
      transfrontal intracranial approach with superior orbital craniotomy for wide
      exposure. One of these three cases is a typical example for the simple anterior
      orbitotomy which is a useful operative approach for patients with solid space
      occupying lesions in the superior part of the orbital cavity. Another patient
      with a hydatid cyst in orbital cavity was operated successfully via a simple
      anterior orbitotomy. The third patients was 6 years old and shows that the
      procedure can be used easily in children as well.

PMID- 15257487
TI  - Decompression without anterior transposition: an effective minimally invasive
      technique for cubital tunnel syndrome.
AB  - Cubital tunnel syndrome represents the second most common compression neuropathy
      in the upper limb. There are three main surgical procedures to deal with this
      issue, namely simple decompression, medial epicondylectomy and anterior
      transposition. Nevertheless, optimal surgical treatment is still open to
      question. In the past three years we performed decompression of the nerve with or
      without external neurolysis and epineuriotomy on 52 patients (55 extremities).
      Preoperative diagnostic procedures included functional hand status,
      neurophysiological evaluation, X-ray of the elbow and neurosonography. Patients
      were then divided into three groups according to the staging criteria of Dellon.
      After an average follow-up of 13 months, the outcome was evaluated by complete
      examination of hand function, electrophysiological studies and interview with the
      patients. Postoperatively, two-point discrimination as well as strength improved
      significantly. Postoperative grip was 28.78 kg (79.8 % of the other hand),
      compared to 20.31 kg (58 % of the other hand) preoperatively (p = 0.000).
      Evaluation of each stage individually showed that the best functional outcome was
      achieved by the minimum-staged group with improvements in strength and sensory in
      all patients and total relief in two-thirds. In the severe-staged group,
      improvement could still be found in 75 % of the patients. Evaluation of
      conduction velocities showed highly significant improvements for both motor and
      sensory conduction velocities. In summary, simple decompression, if necessary
      modified with external neurolysis and epineuriotomy, showed high success rates in
      all stages. Decompression is a minimally invasive procedure, but very effective
      for mild as well as for severe cases and therefore the optimal treatment in
      cubital tunnel syndrome.

PMID- 15257488
TI  - A newly designed disposable introducer sheath for a ventricular fiberscope.
AB  - We have developed a disposable plastic introducer sheath for use with a flexible
      endoscope during intraventricular procedures. The sheath is composed of a thin
      polypropylene tube passing through the center of a plastic stopper. The tube
      serves as a sheath through which the fiberscope is introduced into the ventricle.
      The stopper seats in the burr hole and prevents downward and lateral movement of
      the tube. The sheath can be placed safely in the ventricle with a drainage
      catheter used as an introducing guide. We used this sheath system in 10 patients
      and found it very useful. Manipulation of the fiberscope was not hindered,
      copious irrigation was allowed, and the sheath remained stable on the skull. This
      new introducer sheath may contribute to the increased use of a flexible endoscope
      in neuroendoscopic procedures.

PMID- 15257489
TI  - Transparent microballoon dissection in the surgical treatment of brain tumors.
AB  - In spite of maximal microsurgical efforts, perilesional neural tissue can be
      injured by surgical instruments in the process of the separation and dissection
      of tumors. We hypothesized that transparent microballoon dissection could be
      helpful in the gentle separation of brain tissue from tumor by minimizing
      cerebral damage, and in separating sulcal and cisternal walls during surgical
      interventions on brain masses. We used the transparent microballoon dissection
      technique in 3 primary cases and 4 metastatic brain tumors that were verified
      with computed tomography (CT) and magnetic resonance imaging (MRI). Gentle
      separation of tumor from surrounding brain, reduction of cerebral damage, and
      separation of sulcal and cisternal walls were feasible in all patients.
      Postoperative CT and MRI showed satisfactory results in reducing perilesional
      cerebral damage. The transparent microballoon inflation technique is a useful
      microsurgical method for the gentle separation of tumors from surrounding brain
      tissue, minimizing cerebral damage, and separating sulcal and cisternal walls
      during surgical interventions for brain masses. Our conclusion is that using the
      microballoon dissection method may be suitable in microneurosurgical practice.

PMID- 15257490
TI  - [Multicentric tumor documentation in the ENT].

PMID- 15257491
TI  - [Development of a database system for multicentric ENT tumor documentation].
AB  - BACKGROUND: Multicentric clinical studies have a great impact on progress in
      diagnostics and therapy in oncology. However, multicentric retrospective clinical
      trials require a common documentation standard. METHODS: A network enabled tumor
      documentation program based on a relational database system was developed for the
      management of multicentric clinical studies. This system is designed for the
      documentation of treatment and follow-up. CONCLUSION: The use of a computer
      supported documentation system minimizes documentation effort and error
      frequency. However, communication with cancer registries is still an unsolved
      problem.

PMID- 15257492
TI  - [3D-Visualisation of the middle ear by computer-assisted post-processing of
      helical multi-slice CT data].
AB  - Post-processing of CT-data allows non-invasive 3D-Visualisation of the middle ear
      for diagnosis and surgical planning. In this study different post-processing
      techniques and the clinical application of a 3D-postprocessing algorithm in a
      large number of patients are presented. 20 normal patients, 6 dissected temporal
      bones and 213 patients with suspected middle ear pathology were examined using a
      low-dosage Multi-Slice CT protocol. Virtual endoscopic views of the middle ear
      and 3D-images of the ossicles were generated using a standardised algorithm.
      Evaluation of the image quality was performed. The virtual views of the dissected
      temporal bones were compared to real views. In 32 patients high-quality 3D-models
      of the individual anatomical structures were generated and displayed using
      different visualisation techniques. The standardised and evaluated method enabled
      visualisation of the normal middle ear anatomy. Assessment of different
      pathologies, especially malformation, trauma, implants and postoperative
      alterations, was facilitated. The high-quality 3D-models allowed precise imaging
      of the anatomical structures. 3D-Visualisation of the middle ear using CT-data is
      beneficial for radiological diagnosis and surgical planning in cases of complex
      middle ear pathology as a complementary examination technique.

PMID- 15257493
TI  - [Myospherulosis of the middle ear -- a rare differential diagnosis of
      cholesteatoma].
AB  - BACKGROUND: Myospherulosis is a chronic-inflammatory lesion that is most commonly
      iatrogenic of origin and occurs in tissues exposed to petrolatum-based products.
      The disease does not exhibit characteristic symptoms and is therefore not
      diagnosed in some instances. In previous otorhinolaryngological studies,
      myospherulosis was mainly found in paranasal sinuses, while only four otitic
      cases have been reported. METHODS: A 48-year-old female Egyptian patient suffered
      from bilateral chronic otitis media that had been treated in Egypt by
      tympanoplasty. The patient presented few months later at the university ENT
      department (Mainz) with deteriorated otorrhea and otalgia. Clinical, otoscopical,
      and radiological examination led to the diagnosis of cholesteatoma. During
      revision surgery of the right side, ointment-like material was found, which was
      embedded in granulation tissue. Middle ear biopsies were taken from both sides
      and routinely processed for standard histological examination and transmission
      electron microscopy. RESULTS: Histological examination of the right middle ear
      biopsy showed cystic tissue spaces lined by histiocytes and foreign-body giant
      cells in a fibrous stroma. In the tissue spaces, scattered debris and sac-like
      structures containing round spherules of aggregated erythrocytes were found. In
      addition, erosion of adjacent bone matrix was seen. Diagnosis of myospherulosis
      was made. By contrast, histological evaluation of the left middle ear biopsy
      revealed cholesterol granuloma. CONCLUSION: Myospherulosis of the middle ear has
      been hitherto diagnosed in a very few otitic cases, but might be overlooked as it
      mimicks other chronic proliferative and inflammatory lesions such as
      cholesteatoma in the present case. Thus myospherulosis should be considered in
      otitic cases with a suspicious history (exposure to petrolatum-based products).
      Furthermore, patients with myospherulosis have a significantly higher likelihood
      of developing postoperative complications. Since the lesion exhibits distinct
      histological findings, microscopy plays a central role for the diagnosis of this
      important disease.

PMID- 15257494
TI  - [The cartilage guide: a solution for anchoring a columella-prosthesis on
      footplate].
AB  - BACKGROUND: A torp (columella-prosthesis) is the typical ossicular reconstruction
      in cases of a destroyed stapedial arch. Yet, many unsatisfactory hearing results
      are due to the lack of a stable, reliable anchoring of the base of the prosthesis
      on the footplate. Some solutions have been postulated, amongst them the
      perforation of the footplate with a tiny spike at the lower end of the
      prosthesis, which, however, many otosurgeons regard as too dangerous for the
      inner ear. Specially designed silicone sheets cannot guarantee a permanent guide
      of the columella. METHODS: From our good experience with cartilage in different
      reconstruction procedures, we therefore developed a cartilage guide for the oval
      window niche. An oval 2,5 x 3,5 mm cartilage with a central hole is cut out of a
      thin (0,2 - 0,3 mm) cartilage plate with a help of a cartilage punch, which we
      had designed in collaboration with Heinz Kurz manufacture. The cartilage is
      placed into the oval niche and its hole guides the prosthesis onto the centre of
      the footplate. RESULTS: Temporal bone experiments demonstrated a reliable sound
      transport through this guide. Revision surgery revealed a stable ingrowth of the
      cartilage plate into the oval niche, its perforation securely guiding the
      prosthesis similar to a piston on to the footplate. The first short time hearing
      results (max. 1 year) in 22 patients confirmed the acoustic quality of this
      stabilisation of a columella on the footplate as compared to a matched control
      group. CONCLUSIONS: The stabilization of the columella with a cartilage-guide
      might solve one of the many problems with unsatisfactory hearing results after
      the reconstruction of a completely destroyed ossicular chain.

PMID- 15257495
TI  - [Results with the Contour cochlear implant in patients with cochlear
      otosclerosis].
AB  - BACKGROUND: Results after cochlear implant surgery may be complicated by
      postoperative facial nerve stimulation. Aim of the study presented was to
      evaluate postoperative results in implanting the straight Nucleus electrode array
      and the preformed Contour array in patients with deafness due to cochlear
      otosclerosis. METHODS: A retrospective analysis of intra- and postoperative
      reports of all patients with cochlear otosclerosis was carried out. Results with
      the Nucleus straight electrode array and the Contour array were compared with
      regard to postoperative facial nerve stimulation. RESULTS AND CONCLUSION: None of
      the Contour patients (n = 7) presented with postoperative facial nerve
      stimulation. This is in contrast to the majority (4 of 6) of patients being
      implanted with the straight electrode array. Our results indicate that the use of
      the Contour array is advantageous in patients being at risk for facial nerve
      stimulation. In addition intraoperative reports suggest a more reliable insertion
      of the Contour electrode array in cochlear otosclerosis with partial
      obliteration.

PMID- 15257496
TI  - [The cartilage conserving concept of surgical tracheostomy].
AB  - BACKGROUND: Most techniques of tracheostomy include a resection or at least
      incision of the cartilage himself. This may result in local tracheomalacia and
      chondritis. METHODS/PATIENTS: We performed 48 tracheotomies (173 cases were
      totally performed in our in 2002 excluding laryngectomie patients) in with
      horizontal incision between 2 (nd) and 3 (rd) ring sparing all cartilage. The
      detailed technique is described and the (endoscopic controlled) follow-up data
      showed no complications. We called this techniques the visor-tracheostomy.
      RESULTS: It is shown, that a modified concept of conservating cartilage while
      doing tracheostomy is easy to perform without any increasing in time and costs.
      The most important thing is to choose the right incision range. CONCLUSIONS: It
      seems to us, that healing of these tracheotomies is better and secondary
      complications as stenosis of trachea should be less instead of the cases where
      Bjork-flaps or simply local resection were performed.

PMID- 15257497
TI  - [Long-term results of laser-tonsillotomy in obstructive tonsillar hyperplasia].
AB  - BACKGROUND: Carbon-dioxide-laser-tonsillotomy is reconsidered as a procedure to
      relieve patients in early childhood from obstructive symptoms caused by tonsillar
      hyperplasia such as snoring or sleep apnea without influencing the immunological
      function. METHODS AND PATIENTS: The protruding part of the tonsils was removed by
      a CO (2)-laser delivering 10 - 15 W. During 1993 to 2003, 83 children received
      laser-tonsillotomy, combined with adenoidectomy 51 children were available for
      follow-up with a standard questionnaire. The parents were surveyed in average 39
      months postoperatively. 5 patients required a subsequent tonsillectomy due to a
      recurrence of tonsillar hyperplasia. Histological investigations were done. 15
      children were reevaluated by clinical examination. RESULTS: Most of the patients
      were relieved from obstructive symptoms. There was no occurrence of postoperative
      hemorrhage or peritonsillar abscesses. The histological investigations on the
      specimens from later performed tonsillectomy (n = 5) showed no evidence of
      scarring opened crypts. The clinical examination did not reveal any signs of
      chronic infections. CONCLUSION: The tonsillotomy by carbon-dioxide-laser appears
      as a suitable and safe technique for the treatment of tonsillar hyperplasia
      without severe throat infection in early childhood.

PMID- 15257498
TI  - [The interesting case -- case number 61].
AB  - A 58-year-old patient presented after having undergone radiation therapy,
      afterloading therapy and chemotherapy of a T4 nasopharynx carcinoma. On the basis
      of the MRI findings, local tumour recurrence was suspected. The samples taken
      from the nasopharynx and the left maxillary sinus confirmed this diagnosis.
      Neuroradiological imaging showed that the tumour extended into the area around
      the left skull base and also revealed an irregular formation located in the left
      temporal flap. Therefore not only tumour resection (Fisch approach type C) but
      also a temporal craniotomy was indicated in order to determine the degree of
      intracerebral tumour extension. The dura mater, which had been intact, was
      intraoperatively opened and revealed vital brain tissue, i. e. tumour
      infiltration had not reached the brain. It was concluded that the radiological
      findings probably indicated a postradiogenic necrosis of the temporal flap. The
      presented case illustrates the rare differential diagnostic procedure carried out
      in a patient with radiogenic necrosis while taking into account the possibility
      of local tumour infiltration into the brain parenchyma.

PMID- 15257499
TI  - [Haemorrhoidectomy: conventional excision versus resection with the circular
      stapler. Prospective, randomized study].
AB  - BACKGROUND AND OBJECTIVE: The goal of this study was to compare two surgical
      methods of treating for haemorrhoids that aim at closure of the wound: resection
      with a circular stapler and a conventional, closed haemorrhoidectomy. PATIENTS
      AND METHODS: 80 patients (41 males, mean age 47,1 years) with haemorrhoids stage
      3 were randomized and treated with stapler haemorrhoidectomy (test group; n = 40)
      or had an haemorrhoidectomy according to Fansler and Anderson (control group; n =
      40). Following a standardized study protocol we compared postoperative results on
      the operating day and one week, six weeks, six months and one year afterwards uni
      and multivariate analysis and we also calculated the costs. RESULTS: The stapler
      haemorrhoidectomy proved to be the method causing significantly reduced pain in
      the early postoperative period so that the patients needed less pain relief. They
      were able to return to work earlier. One year after stapler haemorrhoidectomy
      there were three episodes of postoperative bleedings that required intervention,
      one in the control group. Six patients still had haemorrhoids stage 3, six
      patients over the age of 65 had persistent anal incontinence (I degrees according
      to Parks) with proven sphincter dysfunction and disturbances in voiding their
      bowel with resulting deterioration of quality of life, significantly more
      frequent than in the control group. CONCLUSIONS: Stapler haemorrhoidectomy cures
      stage 3 haemorrhoids on a long term basis in 84.2 % of patients, costing less
      than all alternative treatments. In some cases, it can be associated with
      postoperative complications.

PMID- 15257500
TI  - [Clinical and haemodynamic results after repeat valvotomy of the mitral valve
      using the Inoue balloon. A comparison with the results after primary valvotomy].
AB  - BACKGROUND AND OBJECTIVE: Percutaneous mitral valvotomy (MVT) with the Inoue
      balloon is the most frequently performed therapeutic alternative to surgical
      commissurotomy in patients with symptomatic mitral valve stenosis. Few data are
      available on the results of repeat MVT. PATIENTS AND METHODS: We compared the
      immediate and 3-month results of all patients who had a repeat MVT (n = 39) with
      those who had a primary intervention (n = 1,117) in our institution between
      February 1989 and January 2001. Mean age of the 31 women and 8 men with repeat
      MVT was 53 +/- 14 years at the first and 57 +/- 14 years at the second
      intervention performed 3 - 10 years later. RESULTS: Following primary
      intervention the invasively assessed mitral valve are (MVA) had increased from an
      average of 1.0 +/- 0.2 cm(2) to 1.7 +/- 0.4 cm(2). Echocardiography three months
      after the intervention revealed a MVA of 1.7 +/- 0.3 cm(2). Repeat MVT resulted
      in an immediate increase of MVA from 1.0 +/- 0.2 cm(2) to 1.6 +/- 0.4 cm(2),
      after 3 months the average MVA was 1.6 +/- 0.3 cm(2). According to the NYHA
      classification clinical symptoms had improved on average from 2.6 to 1.6 three
      months after primay intervention and from 2.8 to 2.1 three months following the
      repeat procedure. The incidence of significant procedure-related complications
      was less than 3 % for both primary and repeat MVT. CONCLUSION: The clinical and
      hemodynamic results demonstrated in our patients suggests repeat MVT as the
      treatment option of choice in mitral restenosis after previous balloon
      intervention, if mitral valve morphology is still suitable.

PMID- 15257501
TI  - [Paraparesis of the lower extremities after acute aortic dissection and a
      thoracic meningioma].
AB  - HISTORY AND CLINICAL FINDINGS: A 70-year-old woman with acute chest pain was
      admitted to a hospital in stable cardiovascular conditions. The patient had no
      history of cardio-circulatory disease. INVESTIGATIONS: An acute myocardial
      infarction was excluded by ECG and blood tests. A computed tomography (CT)
      revealed an aortic dissection (Stanford type A) which extended to the left
      subclavian artery. TREATMENT AND COURSE: She was transferred to our institution
      and underwent urgent operation during which the ascending aorta and the proximal
      arch were replaced by a prosthesis. A few days after surgery, she developed
      progressive paresis of both legs. A control CT scan of the aorta revealed no
      evidence of a persisting aortic dissection. However, magnetic resonance
      tomography showed a meningioma of the thoracic spinal cord. The patient underwent
      surgical resection of the meningioma and her neurological symptoms diminished
      over the next few days. CONCLUSION: Besides spinal ischemia, paresis of both legs
      after acute aortic dissection may be caused by rare lesions such as a thoracic
      meningioma.

PMID- 15257502
TI  - [Suppressor T-cells: immunologic regulator cells and clinical perspectives].
AB  - Regulatory T cells modulate immune responses in different clinical settings.
      Here, we summarize the role of CD4(+)CD25(+) regulatory T cells in autoimmunity,
      transplantation, infectious diseases and tumor immunity.

PMID- 15257503
TI  - [Risks and side effect reactions during therapy with TNF-alpha blockers. An
      immunologic analysis].

PMID- 15257504
TI  - [Prevention and treatment of deep vein thrombosis with ximelagatran].

PMID- 15257505
TI  - [Medicine is my lawful wife, literature my mistress. The 100th anniversary of the
      death of Anton Tschechow].

PMID- 15257506
TI  - [Abridged guideline for management of dyspepsia. Article from DMW 18/2004].

PMID- 15257510
TI  - Myasthenia gravis: diagnostic mimics.
AB  - The clinical hallmark of myasthenia gravis (MG) is fluctuating, painless weakness
      of muscles that most often affect extraocular, lower bulbar, or limb musculature.
      Predicting the probability of successful treatment for the patient assumes that
      the physician has made an accurate diagnosis. In this review, the practical
      differential diagnosis of MG is reviewed from the perspective of conditions (at
      presentation of symptoms and signs) that may mimic the disorder. The differential
      diagnosis includes disorders that limit eye movements (with or without associated
      diplopia), cause false-positive laboratory studies, and mimic MG but have normal
      eye movements. The differential diagnosis includes disorders that affect the
      upper brainstem, cranial nerves, neuromuscular junction, muscles, or local orbit
      anatomy. Nonneurological systemic diseases (i.e., encephalopathy, sepsis) can
      produce fluctuating ptosis or eye movements that can occasionally be confused
      with MG. Although MG is considered often in the differential diagnosis of
      weakness or fatigue symptoms that lack a correlate on neurological examination
      (subjective fatigue, breakaway weakness, chronic fatigue syndrome), MG is almost
      never found.

PMID- 15257511
TI  - Lambert-Eaton myasthenic syndrome.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is an idiopathic or paraneoplastic
      syndrome producing antibodies against presynaptic voltage-gated P/Q calcium
      channels. This decreases calcium entry into the presynaptic terminal, which
      prevents binding of vesicles to the presynaptic membrane and acetylcholine
      release. LEMS is most often associated with small cell lung cancer, although
      idiopathic presentations comprise approximately 40% of the cases. The most common
      initial complaint is proximal muscle weakness involving the lower extremities
      more than the upper extremities. Depressed deep tendon reflexes and autonomic
      dysfunction are frequently present. Involvement of the bulbar or respiratory
      muscles is rare. Diagnosis is confirmed by electrophysiological testing, which
      demonstrates small compound muscle action potentials and facilitation with
      exercise or 20-Hz repetitive stimulation. A serum test for voltage-gated calcium
      channel antibodies is commercially available. Treatment involves removing the
      cancer associated with the disease. If cancer is not found, immunosuppressive
      medications and acetylcholinesterase inhibitors are used with moderate success.
      Patients with idiopathic LEMS should be screened every 6 months with chest
      imaging for cancer.

PMID- 15257512
TI  - Botulism: update and review.
AB  - Botulism is both an old and an emerging disease. Over 100 years ago, the classic
      food-borne type was found to be caused by ingesting contaminated food containing
      the toxin produced by a bacteria. In the first half of the 20th century a second
      form, wound botulism, was discovered. Three additional forms (infant, hidden, and
      inadvertent) were first described in the last quarter of the 20th century. Our
      understanding of how botulinum toxin blocks the release of acetylcholine at the
      neuromuscular junction has been clarified in the past 10 years. In the past 20
      years, we have witnessed one of the strangest of all ironies in the history of
      medicine. The very lethal botulinum toxin is now being used as a treatment in an
      expanding list of disorders. Research is advancing in several directions. These
      new avenues include improved methods of preventing and treating botulism and
      additional novel uses of botulinum toxin as a therapeutic agent. In this article,
      the five clinical forms of botulism, the actions of botulinum toxins,
      electrodiagnostic methods, treatments, and possible future directions are
      discussed.

PMID- 15257513
TI  - Pearls and pitfalls in the therapeutic use of botulinum toxin.
AB  - Botulinum toxin is a potent toxin and powerful therapeutic tool. Botulinum toxin
      has therapeutic application in the treatment of a host of neurological,
      ophthalmologic, gastroenterological, urologic, and dermatologic conditions.
      Although there are issues specific to each disorder for which botulinum toxin
      therapy is employed, there are several common principles. This article reviews
      several of these general principles by addressing common questions that arise in
      the therapeutic use of botulinum toxin. Areas of focus include patient selection,
      drug preparation and delivery, use of electromyography to guide injections, drug
      resistance, and organization of a therapeutic botulinum toxin clinic.

PMID- 15257514
TI  - Snake venoms and the neuromuscular junction.
AB  - There are approximately 420 venomous species of snakes living on the earth. Their
      venoms, each unique, can affect multiple organ systems. The venoms have a
      predilection for the peripheral nervous system where the neuromuscular junction
      is a favorite target. Those venoms affecting the release of acetylcholine from
      the presynaptic membrane are called beta-neurotoxins and those affecting the
      postsynaptic membrane are called alpha-neurotoxins. alpha-Bungarotoxin has been
      used in quantitative studies of acetylcholine receptor density and turnover and
      for the assay of antibodies directed against the acetylcholine receptor. A unique
      feature of timber rattlesnake venom is its ability to cause clinical myokymia.
      This likely results from a blockade of voltage gated K+ antibodies.

PMID- 15257515
TI  - Tick paralysis.
AB  - Tick paralysis results from inoculation of a toxin from tick salivary glands
      during a blood meal. It is a relatively uncommon neuromuscular disease with a
      higher prevalence among young girls, although older men who get exposed to ticks
      may also be affected. It typically presents as an acute ascending paralysis
      occurring a few days after tick attachment and may result in respiratory failure
      and death. Patients may report minor sensory symptoms but constitutional signs
      are usually absent. Deep tendon reflexes are usually hypoactive or absent and
      ophthalmoplegia and bulbar palsy can occur. Children may be ataxic.
      Electromyographic studies usually show a variable reduction in the amplitude of
      compound muscle action potentials but no abnormalities of repetitive nerve
      stimulation studies. These appear to result from a failure of acetylcholine
      release at the motor nerve terminal level. There may be subtle abnormalities of
      motor nerve conduction velocity and sensory action potentials. Removal of the
      tick results in the very rapid reversal of clinical and physiologic deficits,
      quicker with North American ticks than with the Ixodes species seen in Australia.

PMID- 15257516
TI  - Nerve agents: pathophysiology and treatment of poisoning.
AB  - Nerve agents, the deadliest of the classical chemical warfare agents, primarily
      function as acetylcholinesterase inhibitors and cause a rapidly progressive
      cholinergic crisis. Because of the speed of onset of the syndrome, treatment must
      be rendered emergently and will most likely be performed by first responders.
      Neurologists should be familiar with the pathophysiology and treatment of
      syndromes caused by nerve agents, not only to assist with the hospital care of
      these patients but also to serve as resources to their local medical communities
      in preparation for chemical terrorism.

PMID- 15257517
TI  - Organophosphate poisoning.
AB  - Organophosphates are commonly used as pesticides around the world. Exposures to
      organophosphates cause a significant number of poisonings and deaths each year.
      Organophosphates bind and inhibit cholinesterase enzymes. Acute toxicity
      manifests as a cholinergic crisis with excessive glandular secretions, altered
      mental status, and weakness. Several delayed syndromes have also been associated
      with organophosphate exposure, including a myasthenic-like syndrome, peripheral
      neuropathies, neuropsychiatric abnormalities, and extrapyramidal disorders.
      Clinical features and management of organophosphate poisoning is reviewed with
      emphasis on those affecting the central and peripheral nervous system.

PMID- 15257519
TI  - [The efficiency and cost-utility ratio of interferon beta in the treatment of
      multiple sclerosis in Andalusia].
AB  - INTRODUCTION: The availability of the interferon beta in its three forms at the
      moment available in our country and of glatiramer acetate has marked a point of
      flexion in the natural history of multiple sclerosis (MS), but the high cost of
      these treatments cause that its use is questioned. In this work we have studied
      the effectiveness and efficiency of the processing with interferon beta, and the
      cost-utility of these treatments in MS in Spain has been also analyzed. PATIENTS
      AND METHODS: For this work we studied 102 patients affected of RR MS, treated
      with the three interferons beta which we have available in our country. We used
      as control 330 patients who had participated in the pivotal clinical interferon
      trials with both interferon beta 1a. In these patients in addition to
      effectiveness data, we have studied the disability measured as area below curve
      and the quality of life (AVACs). We also calculated the economical costs,
      considering the relation cost-utility in our country. RESULTS: Besides to confirm
      the data of effectiveness of three interferons, in this study a saving of 23
      days/year is demonstrated what corresponds to 0.063 AVACs. The additional cost of
      interferons is greater than the avoided cost until the fifth year of treatment in
      which the tendency is reversed in favor of the group of treated patients, if we
      assume that the same effectiveness that we found in the first years is maintained
      in the long term. CONCLUSION: The use of the treatment with interferon beta is
      justified by its effectiveness, efficacy and efficiency. The additional cost of
      the treatment will be compensated in the long term if the effectiveness of the
      interferon beta is maintained.

PMID- 15257520
TI  - [Mnemonic performance in patients following surgery to treat an aneurysm
      affecting the anterior circulation of the brain].
AB  - INTRODUCTION: Patients submitted to surgery to treat a brain aneurysm, who have
      suffered a subarachnoid haemorrhage, sometimes present cognitive disorders that
      can affect their social, familial, academic or occupational relationships. Memory
      disorders are frequent, although other cognitive functions may also be affected.
      AIMS: The purpose of this research work was to study performance in logical
      verbal memory and visual-constructional memory in subjects following a surgical
      intervention (at least a year ago) to treat an aneurysm in the territory of the
      anterior circulation of the brain. We also wanted to analyse whether the location
      of the aneurysm in the brain had any effect on memory performance. PATIENTS AND
      METHODS: We examined a sample of 24 adult subjects of both sexes, with no
      previous history of cognitive or psychiatric disorders, who had undergone
      surgical treatment of brain aneurysms in the middle cerebral, anterior
      communicating and posterior communicating arteries. Neuropsychological tests were
      performed to assess the general cognitive status, as well as logical verbal and
      visual-constructional memory. RESULTS: 79% of the patients present a general
      cognitive status within the range of what could be considered to be normal. In
      logical verbal memory, 92% present performances within the limits of the expected
      range of values and 83% did the same in visual-constructional memory. Depending
      on the location of the aneurysm, significant differences were only found in the
      delayed evocation of logical verbal material. CONCLUSIONS: A year after the
      intervention, most of the patients present a pattern of normality in the general
      cognitive status, and in logical verbal and visual-constructional memory. Yet, in
      spite of the good neurological resolution, alterations to memory are still to be
      found, although less frequently. The anatomical location of the aneurysm in the
      brain affects performance in tasks involving delayed logical verbal memory.

PMID- 15257518
TI  - High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1)
      with microdeletions caused by somatic recombination of the JJAZ1 gene.
AB  - Detailed analyses of 20 patients with sporadic neurofibromatosis type 1 (NF1)
      microdeletions revealed an unexpected high frequency of somatic mosaicism (8/20
      [40%]). This proportion of mosaic deletions is much higher than previously
      anticipated. Of these deletions, 16 were identified by a screen of unselected
      patients with NF1. None of the eight patients with mosaic deletions exhibited the
      mental retardation and facial dysmorphism usually associated with NF1
      microdeletions. Our study demonstrates the importance of a general screening for
      NF1 deletions, regardless of a special phenotype, because of a high estimated
      number of otherwise undetected mosaic NF1 microdeletions. In patients with
      mosaicism, the proportion of cells with the deletion was 91%-100% in peripheral
      leukocytes but was much lower (51%-80%) in buccal smears or peripheral skin
      fibroblasts. Therefore, the analysis of other tissues than blood is recommended,
      to exclude mosaicism with normal cells in patients with NF1 microdeletions.
      Furthermore, our study reveals breakpoint heterogeneity. The classic 1.4-Mb
      deletion was found in 13 patients. These type I deletions encompass 14 genes and
      have breakpoints in the NF1 low-copy repeats. However, we identified a second
      major type of NF1 microdeletion, which spans 1.2 Mb and affects 13 genes. This
      type II deletion was found in 8 (38%) of 21 patients and is mediated by
      recombination between the JJAZ1 gene and its pseudogene. The JJAZ1 gene, which is
      completely deleted in patients with type I NF1 microdeletions and is disrupted in
      deletions of type II, is highly expressed in brain structures associated with
      learning and memory. Thus, its haploinsufficiency might contribute to mental
      impairment in patients with constitutional NF1 microdeletions. Conspicuously,
      seven of the eight mosaic deletions are of type II, whereas only one was a
      classic type I deletion. Therefore, the JJAZ1 gene is a preferred target of
      strand exchange during mitotic nonallelic homologous recombination. Although type
      I NF1 microdeletions occur by interchromosomal recombination during meiosis, our
      findings imply that type II deletions are mediated by intrachromosomal
      recombination during mitosis. Thus, NF1 microdeletions acquired during mitotic
      cell divisions differ from those occurring in meiosis and are caused by different
      mechanisms.

PMID- 15257521
TI  - [Conventional and quantitative electroencephalography in patients with Steinert's
      myotonic dystrophy].
AB  - INTRODUCTION: Steinert's myotonic dystrophy (SMD) is a systemic-type dominant
      autosomal disease, with variable clinical expression. Recent magnetic resonance
      studies conducted in patients with this disease have described the presence of
      lesions in the white matter of the brain and there have also been reports of a
      correlation between these and the presence of cognitive disorders. Nevertheless,
      very little work has been published about the electroencephalographic (EEG)
      findings in this disease. PATIENTS AND METHODS: In this study both conventional
      and quantitative EEG were performed on 10 patients with SMD aged between 17 and
      50 years. RESULTS: 90% of the patients showed a posterior alpha rhythm that was
      disorganised but which reacted on opening and closing the eyes, as well as the
      presence of continuous theta activity over the base activity that was bilaterally
      more pronounced towards the frontal-central regions. In the quantitative analysis
      we observed an increase in the absolute energies for the slow bands and a
      decrease for the fast bands on the frequency spectrum. In most patients (80%)
      spectral peaks were found within the theta range of frequencies as a correlate of
      the slow activity observed in the conventional analysis. CONCLUSIONS: It can be
      concluded that a quantitative EEG could be useful in the study of what, for many
      years, has been considered to be a 'neuromuscular' disease and that the use of
      other more precise methods, such as cerebral coherence and brain electrical
      tomography, could shed new light on the functional management of these patients.

PMID- 15257522
TI  - [The prevalence of sleep disorders among adolescents in Cuenca, Spain].
AB  - INTRODUCTION: A number of different studies have shown that there is a high
      prevalence of sleep disorders among adolescents. These are often cited as being
      due to psychological, hormonal or pubertal factors, as well as inadequate sleep
      habits. AIMS: The aims of this study were to determine the prevalence of sleep
      disorders in the adolescent population and to describe their sleep habits and the
      relationship between sleep disorders and daytime tiredness or drowsiness.
      SUBJECTS AND METHODS: We conducted an epidemiological, observational, cross
      sectional study in a sample of schoolchildren studying the 1st and 4th years of
      compulsory secondary education by means of a self-administered anonymous
      questionnaire. Insomnia was diagnosed using DSM-IV criteria. RESULTS: Of a total
      number of 1155 children, 537 were males and 618 were females, with a mean age of
      14.03 +/- 1.86 years. They sleep an average of 8 h 18 m during the week and 9 h
      40 m at the weekend. Poor quality sleep was reported by 38.55%, 23.1% had
      difficulty in getting to sleep, 38.2% woke up during the night and 15.9% woke up
      too early. 17.7% reported some kind of sleep complaint plus some other insomnia
      related symptom; the prevalence of insomnia was found to be 9.9%. Snoring
      (20.5%), talking in their sleep (45.4%) and nightmares (29.5%) were the most
      frequent parasomnias. 53% of them complained of excessive sleepiness during the
      day. Insomnia is more frequent in older adolescents, with a family history of
      similar disorders, among those who smoke and drink and sleep fewer hours at the
      weekend; those with insomnia present more symptoms of anxiety and depression, as
      well as more daytime drowsiness. CONCLUSIONS: A number of factors are related to
      the high prevalence of sleep disorders among adolescents, giving rise to their
      being very tired and drowsy during the day. The interruption of their normal
      sleep habits at the weekend and an insufficient number of hours' sleep are
      related to the appearance of insomnia.

PMID- 15257523
TI  - [Neurosonological studies in patients over 80 years old].
AB  - INTRODUCTION: The link between cardiovascular risk factors and carotid
      atheromatosis has been shown to be more important in middle aged subjects than in
      the elderly. AIMS: Our aim was to study the frequency of carotid and intracranial
      atheromatosis in a population over the age of 80 and to compare the presence of
      neurosonological anomalies depending on whether the patients have suffered a
      stroke or not. We also wished to compare the findings according to the sex of the
      patient. PATIENTS AND METHODS: Patients over the age of 80 were studied at our
      Neurosonology laboratory using carotid and transcranial Doppler ultrasonography.
      The patients were analysed according to whether they had suffered an ischemic
      stroke or not. With regard to the carotid, a distinction was made between normal,
      non-significant atheromatosis and significant atheromatosis (stenosis > 50%).
      Intracranially, both the middle cerebral artery (normal, stenosis,
      microangiopathy and post-stenosis) and the basilar artery (normal, stenosis,
      microangiopathy and hyperdynamics) were studied. RESULTS: We recorded data
      concerning 832 patients: 342 males (44.1%), mean age 83.63 +/- 3.25 years, and
      527 (63.3%) with stroke. The carotid study was pathological, with a higher
      frequency in stroke patients (32.1% compared with 41.9%; p = 0.002). The presence
      of atheromatosis was significantly linked to a higher risk of suffering a stroke
      and more intensely to its being more severe. Carotid studies were pathological
      with a higher frequency among males (28.7% compared with 40%; p < 0.001). No
      significant differences were found intracranially in any of the parameters
      analysed. CONCLUSIONS: There is a high frequency of carotid atheromatosis in
      patients over 80 years of age. Regardless of the age, carotid atheromatosis
      appears even more frequently in patients who have suffered a stroke and in males,
      and is significantly associated to the risk of suffering a stroke.
      Intracranially, no differences were found.

PMID- 15257524
TI  - [Cerebral venous thrombosis as the presenting symptom of systemic lupus
      erythematosus].
AB  - INTRODUCTION: Cerebral venous thrombosis (CVT) is an infrequent process in
      systemic lupus erythematosus. We report the case of a female patient whose
      initial manifestation of lupus was a CVT. CASE REPORT: A 30-year-old female who
      presented headaches and diminished visual acuity; on exploring the patient
      bilateral papilloedema was found. Magnetic resonance imaging revealed the
      presence of a venous thrombosis in the superior and transversal longitudinal
      sinus. Complementary explorations showed high levels of antinuclear antibodies
      with leukopenia and proteinuria. Antiphospholipid antibodies were negative.
      Following treatment with anticoagulants, the patient's condition improved both
      clinically and radiologically. Months later a biopsy was performed and revealed a
      grade IV diffuse glomerulonephritis. CONCLUSIONS: In systemic lupus
      erythematosus, phenomena such as CVT can be the initial form of presentation of
      the disease. The presence of antiphospholipid antibodies plays a partial role in
      CVT; other phenomena, such as inflammatory processes, should also be taken into
      account.

PMID- 15257525
TI  - [Dementia with Lewy bodies. A description of a case with a genetic variant].
AB  - INTRODUCTION: Dementia with Lewy bodies represents the third cause of dementia in
      the clinicopathological series reported to date. CASE REPORT: A 79-year-old white
      female with a 3-year history of symptoms of dementia, Parkinsonism and visual
      hallucinations; the symptoms were difficult to control with medication and there
      was a family history of similar clinical pictures of dementia in the paternal
      grandfather, an aunt on the father's side and six siblings. A genetic study was
      not possible. The study thus involves a patient with relatives that may have had
      the pure or mixed variant of these dementias, without the DNA study for
      determining the e4 allele of the gene for apolipoprotein E that has been found
      most frequently in dementia due to Alzheimer.

PMID- 15257526
TI  - [Superficial siderosis of the central nervous system: report of two new cases].
AB  - INTRODUCTION: Superficial siderosis of the central nervous system (CNS) is a rare
      disease characterized by deafness, ataxia and pyramidal dysfunction. It is due to
      hemosiderin deposition in the subpial membranes of the brain, spinal cord and
      cranial nerves. Most cases are secondary to chronic or recurrent bleeding into
      the subarachnoid space. Diagnosis is permitted by magnetic resonance imaging
      (MRI). CASE REPORTS: We report two patients with a chronic, slowly progressive
      cerebellar ataxia and hearing loss. MRI showed T2 hypointense signals in the
      brain, cerebellum and spinal cord diagnostic of superficial siderosis of the CNS.
      Xanthochromia was present in one patient. Evoked potentials showed retrochoclear
      hearing loss. Extensive vascular studies were negative for bleeding sources. One
      patient, treated with oral anticoagulants, benefited from reduction of the
      International Normalized Ratio. CONCLUSION: Due to its rarity, clinical suspicion
      is essential for diagnosis of superficial siderosis of the CNS.

PMID- 15257527
TI  - [Musical memory preserved in an amnesic syndrome].
AB  - INTRODUCTION: In amnesic syndromes, it's usually to see dissociation between
      episodic, semantic and procedural memory. However, a few reports have been found
      about musical memory's processing and the relation with classic memory systems.
      AIM: To describe the musical's abilities preserved in a patient with amnesic
      syndrome and discuss possible neuropsychological and neurobiological bases
      implicated. CASE REPORT: A 28-years-old woman presenting with amnesic syndrome is
      reported. Following a carbon monoxide encephalophaty and subsequent hypoxia she
      remained in coma for 10 days with evidence of bilateral temporal changes, mainly
      affecting basal ganglia areas. The patient showed anterograde amnesia and
      semantic memory impairment, with disproportionately spared musical abilities'
      performance, either music perception (discrimination and recognition of tonal
      melodies, musical sight-reading) or music production (song and instrumental
      performance) or musical memory. CONCLUSIONS: This case suggests that the music
      require elaborate bihemispheric processing and may implicate different forms of
      information processing. The neural network involved in musical memory can be
      different that the declarative memory systems (episodic and semantic).

PMID- 15257528
TI  - [Are symbolic behaviour and neuroplasticity an example of gene-culture
      coevolution?].
AB  - INTRODUCTION AND DEVELOPMENT: The brain size in the Homo genus not only has not
      increased during the last 150,000 years but has also experienced a slight
      reduction in the last 35,000 years. This reduction coincides with the
      generalization of the symbolic culture that was most likely established during
      the Upper Palaeolithic. Therefore, the cognitive capacities characteristic in the
      Homo sapiens could be due to structural and functional changes during the brain
      evolution, rather than an increase of the brain size. Dependence of symbolic
      culture probably required an increase of the learning and memory skills, thus
      demanding, at the same time, an improvement of neuroplasticity. CONCLUSIONS: The
      epsilon3 and epsilon2 alleles of the apolipoprotein E seem to contribute to a
      better synaptic repairing, in relation to the ancestral epsilon4 allele. Mutation
      leading to the epsilon3 allele occurred between 220,000 and 150,000 years ago.
      Its selection and expansion may have continued until a relatively recent period
      that coincides with the emergence and expansion of the complex symbolic culture.
      Other factors favouring neuroplasticity, such as certain polymorphisms and the
      expression increase of certain proteins as reelin, could also have been selected.
      Emergence of the symbolic behaviour and increase of its deriving technical and
      social complexity could have made an intense selective pressure leading to a
      selection of genes that induced an improvement in neuroplasticity. This would
      constitute an example of gene-culture coevolution.

PMID- 15257529
TI  - [Tourette's syndrome].
AB  - OBJECTIVE: To present a general view about update knowledge of Tourette's
      syndrome. METHOD: There is reviewed the literature on the subject without
      presenting a personal series, and there are presented those reported in the
      literature. CONCLUSIONS: Although there are a lot of studies that try to know the
      origin and nature of Tourette's syndrome, as well as the response of tics to the
      action of old and new drugs, it seems that we still have a long way to walk
      before finding solutions for the several diagnostic and therapeutic problems of
      this picture.

PMID- 15257530
TI  - [Guidelines for the scientific and professional development of forensic
      neuropsychology].
AB  - AIMS: The principal aims of this review are: (a) to offer a perspective of the
      principal challenges that forensic neuropsychology handles in its scientific and
      professional development, and the empirical advances that have been developed to
      deal with these challenges; and (b) analyze the potential effects of these
      advances on the application of the discipline in the Spanish legal system.
      DEVELOPMENT: With the purpose of reaching these challenges, a series of
      methodological strategies and instruments, along with specific recommendations
      about the use of currently available procedures and the development of new
      procedures, have been generated within the context of forensic neuropsychology.
      In this paper, we will review: the advances carried out in the different issues
      of interest that currently handles the development of the discipline, including:
      the estimation of premorbid functioning, the development of base rates and norms
      for forensic populations, the detection of malingerers, the ecological validity
      of instruments, and the creation of professional practices; we will analyze the
      potential application of these advances to the assessment of the Spanish forensic
      population; and we will study the principal application areas of forensic
      neuropsychology within the Spanish legal context. CONCLUSIONS: Forensic
      neuropsychology is an emergent discipline that is placed in a key moment of its
      scientific and professional development. This development should be anchored in
      the application of specific scientific, professional, and academic strategies.

PMID- 15257531
TI  - [Applications of verbal dichotic listening in neurological and neuropsychiatric
      clinical practice].
AB  - AIM: To review the most recent data regarding clinical applications of the
      dichotic listening technique in neurology and neuropsychiatry. DEVELOPMENT: The
      technique is described, in addition to the two main cognitive abilities we can
      measure with it. First, language lateralization, following Kimura's model as an
      anatomical explanation of the right ear advantage effect. Second, the attentional
      function, including Kinsbourne's model and the forced attention paradigm from
      Hugdahl as a valuable working tool to evaluate selective attention and executive
      functions. In subsequent sections, a review is offered respecting both types of
      cognitive processes for schizophrenia, depression, dyslexia and Multiple
      Sclerosis, along with data from our laboratory regarding the last illness.
      CONCLUSIONS: The dichotic listening is a useful technique to evaluate the
      integrity of the temporal and frontal lobes, as well as the interhemispheric
      communication across the corpus callosum. Application to the clinical practice
      pretends to incorporate it to the diagnostic, to the description of the
      pathologies profiles and also to the prediction of illness course, resulting
      promising in some cases although with reasonable limits while looking for
      additional research.

PMID- 15257532
TI  - [Identification and early diagnosis of the autistic spectrum disorders].
AB  - AIM: To review the empirical evidence and recommendations for early
      identification and diagnosis of autistic spectrum disorders (ASD). DEVELOPMENT:
      ASD often remains unrecognized and undiagnosed until late preschool age. A
      significant delay of almost 3 years was reported between parents' initial
      concerns about their child and the age of diagnosis. Some research provides
      further evidence that signs of ASD are evident in the first 2 years of life. The
      importance of early diagnosis is that it opens the door to early intervention
      programs which are essentials for the future of these children. Early diagnosis
      can be facilitated most effectively if early detection is made possible. Progress
      has recently been made in the earlier identification of children with ASD. Recent
      researches have identified early behavioural difficulties in social reciprocity,
      joint attention, theory of mind, gaze engagement, social referencing and
      hypersensitivity to sound. Professionals need to be aware and sensitive to these
      behavioural patterns. Their identification would increase the likelihood of a
      reliable early diagnosis. CONCLUSIONS: At present, it is possible to make earlier
      diagnosis of ASD. It is important that health and education professionals in
      childhood know several early manifestations of ASD.

PMID- 15257534
TI  - [Central nervous system disorders caused by the herpes virus. Magnetic resonance
      imaging findings].

PMID- 15257535
TI  - [A review of the literature on the value of magnetoencephalography in epilepsy].

PMID- 15257538
TI  - Interstitial granulomatous dermatitis with arthritis.

PMID- 15257539
TI  - Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma
      of the breast, April 26-28, 2003, Philadelphia, PA.

PMID- 15257540
TI  - PhD graduate training programs in pathology: 2003 report from the American
      Society for Investigative Pathology workshop on pathology graduate education.
AB  - Graduate training is one of the most important activities in which we engage.
      Through PhD training programs in pathology, we continually renew the intellectual
      vigor of our discipline and assure its position as a vibrant force in the life
      sciences. To focus on this important issue, the Education Committee of the
      American Society for Investigative Pathology (ASIP) organized a workshop on April
      11, 2003 for pathology graduate program directors from across the United States
      and Canada. The goals of this workshop were to better define the current models
      of pathology graduate training programs, to identify key issues pertaining to the
      curriculum of pathology training programs and strategies to better market
      pathology graduate training opportunities, and to identify challenges for the
      future. Twenty-three program directors and other faculty interested in pathology
      graduate education, as well as 2 invited PhD students, attended the workshop.
      Workshop participants concluded that the integration of more and better disease
      related education into graduate training programs would attract more and better
      qualified students into pathology career pathways that will ultimately fulfill
      important societal needs and train future leaders of the biomedical research
      community. The ASIP is facilitating this goal by taking a leadership role in
      publicizing educational efforts in pathology and by making systematic use of its
      Website for sharing information about curriculum ideas and materials, as well as
      course syllabi.

PMID- 15257541
TI  - Webcasting pathology department conferences in a geographically distributed
      medical center.
AB  - As academic pathology departments have become increasingly based in large,
      regional medical systems spread across hundreds of square miles, new methods are
      needed to tie these increasingly distributed departments together as integrated
      units. An important part of that integration is the ability to share academic and
      teaching conferences across long distances. In this article we present an
      effective, low-cost webcasting system that has evolved at the University of
      Pittsburgh Medical Center Department of Pathology over the past several years
      based on inexpensive, widely available software. To date, the system has
      broadcast and archived more than 400 conferences and currently serves
      approximately 80 to 100 requests each week. Important factors in the success of
      the program include the creation of a faculty steering committee to control
      resources and manage growth, the availability of informatics faculty and support
      for technical staff, and the decision to operate the service as part of the core
      information technology infrastructure of the department. Webcasting will likely
      become an even more important academic and operational tool in the future as more
      of the department's conferences, seminars, and even working meetings are
      communicated through the webcasting infrastructure.

PMID- 15257542
TI  - Biomorphometric analysis of human prostatic carcinoma by using three-dimensional
      computer models.
AB  - Advances in the detection of carcinoma of the prostate during the last 15 years
      have accounted for a sharp increase and then an abrupt decrease in the incidence
      of the disease. A more recent decline in its mortality rates has been variously
      interpreted as either the success of early detection and improved treatment or
      lead-time bias. The recently reported Prostate Cancer Prevention Trial had an
      overall detection rate that approached the 30%-40% prevalence rates reported in
      autopsy series in which men died of other causes. However, the prognostic
      information that can be obtained from prostate cancer found on biopsy is limited.
      Three-dimensional computer modeling is one technique that allows multiple studies
      on "immortal" prostates to test methods of biopsy sampling accuracy and to assist
      in the determination of the disease's severity. Computer modeling can assess
      detection rates and assesses tumor multifocality and heterogeneity. It can
      provide a more accurate representation of tumor volume, aiding in therapeutic
      decision making, and can assess sampling errors of various biopsy methods. It has
      been shown to be superior to wire-frame technique by immortalizing the original
      shape and dimensions of the surgically excised prostate gland. Moreover, our 3
      dimensional computer modeling system improves upon other systems: It is more than
      a simple extension of the planimetric technique, and it is able to demarcate
      clearly the boundaries of Gleason grades just 1 grade apart.

PMID- 15257543
TI  - Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal
      cancer with and without microsatellite instability.
AB  - Previous studies have identified high numbers of intraepithelial T lymphocytes to
      be associated with good prognosis in various types of cancer. Few studies
      addressing this issue have been published for colorectal cancer. In a simulated
      prospective approach ("phase II prognostic factor study"), all nonmetachronous
      International Union Against Cancer (UICC) stage III colorectal cancers that were
      accessioned in the years 1994 to 1999 were included in the study (152 cases).
      Follow-up information as to vital status and occurrence of metachronous
      metastases could be obtained for all patients in the years 2001 and 2002. CD8+
      intratumoral lymphocytes were quantified after immunostaining and referred to
      tumor cell area (CD8+ densities). Microsatellite status was determined by using
      the Bethesda panel of microsatellite markers. CD8+ densities ranged from 0 per
      square millimeter to 1436 per square millimeter of tumor area in a nonnormal
      distribution that was skewed toward low values. Univariate survival analyses
      revealed the 66th percentile as a stringent cutoff (CD8+high versus CD8+low),
      with CD8+high cases taking a significantly better clinical course. This
      prognostic impact appeared even more pronounced in the subset of patients with
      colon carcinomas who were receiving 5-fluouracil/leucovorin as adjuvant treatment
      (79 patients). Seventeen patients had carcinomas with high microsatellite
      instability (MSI-H). MSI-H-CD8+high cases (n = 11) showed an excellent prognosis,
      with tumor-free survival for 9 of the 11 patients. The prognostic effect of
      CD8+high was retained in Cox regression analyses when including UICC substages
      (IIIA to IIIC). Our results identify CD8+ tumor-infiltrating lymphocytes as a
      promising candidate for further evaluation in the ongoing search for prognostic
      and predictive factors of colorectal cancer, particularly if combined with
      microsatellite status.

PMID- 15257544
TI  - Profiles of the 2 INK4a gene products, p16 and p14ARF, in human reference
      urothelium and bladder carcinomas, according to pRb and p53 protein status.
AB  - The INK4a/ARF locus encodes 2 cell cycle regulatory proteins: p16 and p14(ARF).
      P16 inhibits the activities of cdks, which maintain the retinoblastoma protein
      (pRb) in its active hypophosphorylated state. P14(ARF) blocks MDM2-induced p53
      degradation and transactivational silencing. In this study, we investigated the
      expression of p16 and p14(ARF) in reference human urothelium and in 51 urothelial
      carcinomas (UCs) of all stages and grades, by reverse transcription-polymerase
      chain reaction (RT-PCR). Patterns of p14(ARF) and p16 expression were compared
      with each other and then with patterns of p53 and pRb protein expression,
      respectively, as determined by immunohistochemistry. P14(ARF) and p16 mRNAs were
      present at low levels or were undetectable in reference urothelia and in most
      superficial tumors, whereas they were present at high levels in a subset of
      tumors of advanced stage and high grade. The expression profiles of these 2 mRNAs
      were correlated in all but 4 cases, indicating that the 2 INK4a products may have
      nonredundant functions. Forty-six of the 51 tumors (90%) presented changes to or
      a lack of activation of the p14(ARF)-p53 pathway and were p53 positive (n = 10),
      p14(ARF) negative (n = 23), or both p53 positive and p14(ARF) negative (n = 13),
      suggesting that these 2 components of the pathway may be altered or nonactivated.
      Markedly high levels of p16 mRNA (n = 5) were associated with the absence of pRb
      expression, with the exception of 1 case in which the p16 gene contained a
      deletion mutation. A lack of p16 mRNA or low levels of this mRNA were associated
      with pRb detection in all but 1 case. In invasive UCs, the p16-pRb pathway, the
      p14(ARF)-p53 pathway, or in many cases both pathways were altered or not
      activated, demonstrating the involvement of these pathways in invasive bladder
      tumorigenesis.

PMID- 15257545
TI  - TTF-1 expression is specific for lung primary in typical and atypical carcinoids:
      TTF-1-positive carcinoids are predominantly in peripheral location.
AB  - Thyroid transcription factor (TTF)-1 expression in neuroendocrine tumors (NETs)
      has not been studied as widely as that in non-NETs, with the exception of small
      cell carcinomas, in which TTF-1 is highly sensitive but not specific for a
      primary lung tumor. The reported incidence of TTF-1 expression in pulmonary
      carcinoids has also been highly variable in the literature. To evaluate the
      expression of TTF-1 in NETs and potential value of TTF-1 in distinguishing
      pulmonary NETs from those of extrapulmonary origin, we performed an
      immunohistochemical study by using semiquantitative analysis on formalin-fixed,
      paraffin-embedded sections from 111 NETs, including 80 pulmonary (11 carcinoid
      tumorlets [TLs] or foci of neuroendocrine cell hyperplasia [NEH], 36 typical
      carcinoids [TCs], 17 atypical carcinoids [ACs], 16 large cell neuroendocrine
      carcinomas [LCNECs]), 13 thymic (3 TCs, 8 ACs, 2 LCNECs), 17 gastrointestinal or
      pancreatic (13 TCs, 4 ACs), and 1 ovarian (LCNEC). Pulmonary carcinoids were
      subdivided into those with central and those with peripheral location. TTF-1
      positivity was seen exclusively in pulmonary NETs and was significantly higher in
      NEH or TLs (72.7%) than in TCs (27.8%), ACs (29.4%), and LCNECs (37.5%; P =
      0.03). All extrapulmonary NETs were uniformly negative for TTF-1 staining.
      Interestingly, 12 of 14 TTF-1-positive pulmonary TCs and ACs had a peripheral
      location with spindle cell morphology, as did all cases of TL, a purported
      precursor of peripheral carcinoids. In conclusion, TTF-1 expression was 100%
      specific, though not so sensitive, for the lung primary in TCs and ACs and
      possibly also in LCNECs. Prevalent TTF-1 positivity in TLs and peripheral
      carcinoids suggest that they may be histogenetically distinct from the central
      carcinoids, which are typically composed of TTF-1-negative, more rounded cells.

PMID- 15257546
TI  - Cell-specific regulation of gamma-glutamylcysteine synthetase in human
      interstitial lung diseases.
AB  - The pathogenesis of interstitial lung diseases (ILDs) is known to be associated
      with reactive oxygen and nitrogen metabolites and increased oxidant stress. One
      of the major antioxidants in human lung is glutathione (GSH) and enzymes linked
      to its synthesis. The rate-limiting enzyme of GSH synthesis is gamma
      glutamylcysteine synthetase (gamma-GCS) containing catalytically active heavy
      (gamma-GCSh) and regulatory light (gamma-GCSl) subunits. It can be hypothesized
      that gamma-GCS is the major determinant in explaining reduced GSH levels in
      fibrotic lung disorders. We investigated the regulation of gamma-GCS by
      transforming growth factor beta(1) (TGF-beta(1)) and tumor necrosis factor alpha
      (TNF-alpha) in human lung cells and its expression and distribution in fibrotic
      (biopsy-proven idiopathic pulmonary fibrosis, for instance, usual interstitial
      pneumonia, UIP, n = 15), inflammatory, and granulomatous diseases of human lung
      parenchyma (desquamative interstitial pneumonia, n = 10; ILD associated with
      collagen diseases, n = 10; sarcoidosis, n = 19 and allergic alveolitis, n = 8).
      In human lung alveolar epithelial cells, gamma-GCSh was decreased by TGF-beta(1),
      whereas TNF-alpha caused a transient enzyme induction. In normal lung, gamma-GCS
      was mainly localized to the bronchiolar epithelium. In UIP, the highest
      immunoreactivities were observed in the airway epithelium and metaplastic
      alveolar epithelium, but fibroblastic foci were negative. In sarcoidosis, the
      highest reactivities were detected in the epithelium, alveolar macrophages and
      pulmonary granulomas. gamma-GCS was ultrastructurally localized to the cytoplasm
      of regenerating type II pneumocytes and macrophages. In conclusion, gamma-GCS is
      widely expressed in sarcoidosis and regenerating epithelium but is low in the
      fibrotic areas of usual interstitial pneumonia, probably because of enzyme down
      regulation.

PMID- 15257547
TI  - 15-Lipoxygenase-2 expression in benign and neoplastic lung: an
      immunohistochemical study and correlation with tumor grade and proliferation.
AB  - 15-Lipoxygenase-2 (15-LOX-2) is an arachidonic acid-metabolizing enzyme expressed
      in prostate, lung, skin, esophagus, and cornea. In the benign prostate, it is
      expressed in differentiated secretory epithelial cells, where its enzymatic
      product 15-HETE may regulate transcription by activating the nuclear receptor
      peroxisome proliferator-activated receptor gamma (PPARgamma). 15-LOX-2 and 15
      HETE formation are reduced in prostate carcinoma. The distribution of 15-LOX-2 in
      the normal lung and its expression in lung carcinomas has not been reported and
      was investigated in the current study by using immunohistochemistry and tissue
      microarrays (TMAs). In benign lung, 15-LOX-2 immunostaining was noted exclusively
      in type II pneumocytes, which are known to express PPARgamma. Of 160 lung
      carcinomas, 15-LOX-2 was expressed in non-small cell carcinomas (NSCLC),
      including 33 of 69 (48%) adenocarcinomas, with 10 of 16 (63%) bronchioloalveolar
      carcinomas immunopositive. Fourteen of 55 (25%) squamous cell carcinomas and 2 of
      14 (14%) large cell carcinomas showed weak immunostaining. All 19 neuroendocrine
      tumors were negative. Better differentiated NSCLCs showed greater 15-LOX-2
      expression, with a significant inverse correlation between 15-LOX-2
      immunostaining and tumor grade (P < 0.03). A significant inverse correlation was
      also noted between 15-LOX-2 immunostaining and tumor cell proliferation (Ki-67
      immunostaining; P < 0.0001). These findings suggest a possible role of 15-LOX-2
      in regulating secretory differentiation and proliferation in benign lung and
      NSCLCs, particularly adenocarcinomas.

PMID- 15257548
TI  - Primary pulmonary synovial sarcoma: a clinicopathologic, immunohistochemical, and
      molecular study of 11 cases.
AB  - Primary synovial sarcoma (SS) of the lung is rare and may create diagnostic
      challenges. We reviewed 11 cases of pulmonary SS (PSS) confirmed by the presence
      of a tumor-specific SYT-SSX fusion gene to verify their clinicopathologic
      features including immunohistochemical and genetical profiles. The tumors
      occurred in 4 men and 7 women (age 29 to 81 years; mean age, 58; median age, 50),
      and ranged in size from 2 to 15.5 cm (mean, 9 cm). Of the 11 tumors, 10 were a
      monophasic fibrous type and 1 was a poorly differentiated type. Mitotic rate
      ranged from 8 to 43 per 10 high-power fields. All cases showed at least focal
      immunohistochemical positivity for AE1/AE3, CAM5.2 and/or epithelial membrane
      antigen. High proliferating cell nuclear antigen labeling index (>20%) was found
      in 8 of 10 cases (80%). Eight (90%) of 9 cases were negative for E-cadherin, and
      1 case (10%) exhibited reduced expression of the molecule. The aberrant
      expression of beta-catenin within cytoplasm and/or nuclei was observed in 6 of 9
      (67%) cases. SYT-SSX1 and SYT-SSX2 fusion gene transcripts were detected in 9 and
      2 cases, respectively. In 10 patients with follow-up, 3 (30%) had local
      recurrences, and 4 (40%) developed distant metastases. Five (50%) patients died
      of the tumor 1 to 9 years after surgery, and 5 (50%) were alive and disease-free
      in the period ranging from 3 months to 5.5 years. In conclusion, PSS tends to
      occur in older patients and shows an aggressive behavior probably due to its
      anatomical location and large tumor often resulting in incomplete resection and
      high proliferative activity.

PMID- 15257549
TI  - Expression of a lymphatic endothelial cell marker in benign and malignant
      vascular tumors.
AB  - Tumors of endothelial cell origin are relatively common. Soft tissue tumors and
      numerous subtypes of benign and malignant vascular tumors have been described;
      the histogenesis of many of these tumors is uncertain, and distinguishing between
      benign and malignant vascular tumors, some of which express lymphatic endothelial
      cell markers, can be problematic. In the present study, immunophenotypic
      expression of a novel hyaluronan receptor (LYVE-1), which is expressed by
      endothelial cells of normal lymphatic vessels but not blood vessels, was
      determined in benign and malignant vascular tumors. It was found that, except in
      lymphangiomas, intramuscular hemangiomas, and Masson's hemangiomas, endothelial
      cells in benign blood vessel tumors (including capillary and cavernous
      hemangiomas, glomus tumors, pyogenic granulomas, and epithelioid hemangiomas)
      were negative for LYVE-1, and that all angiosarcomas and Kaposi's sarcomas were
      positive for LYVE-1. Expression of LYVE-1 and other lymphatic endothelial cell
      markers in relatively few vascular neoplasms has implications for the
      histogenesis of these lesions, and may prove useful in distinguishing
      angiosarcoma and Kaposi's sarcoma from most common benign vascular tumors.

PMID- 15257550
TI  - Expression of Epstein-Barr virus in Langerhans' cell histiocytosis.
AB  - Langerhans' cell histiocytosis (LCH) is a proliferative histiocytic disorder of
      unknown etiology. We previously reported that Epstein-Barr virus (EBV) infects
      and proliferates in macrophages, and investigated the possibility that EBV
      exhibits etiologic effects in LCH. To detect EBV expression, paraffin sections
      from 17 LCH cases were examined by mRNA in situ hybridization for EBV BamHIW,
      Epstein-Barr virus nuclear antigen-2 (EBNA2), and Epstein-Barr virus-encoded
      small nonpolyadenylated RNA (EBER1) sequences, and by indirect immunofluorescence
      staining for EBNA2, latent membrane protein 1 (LMP1), and BamHIZ-coding leftward
      reading frame 1 (BZLF1). To detect EBV DNA, polymerase chain reaction (PCR)
      Southern blotting was used. All cases showed positive hybridization signals by
      BamHIW mRNA in situ hybridization. Also, 13 and 14 cases showed positive signals
      for EBNA2 and EBER1 RNA in situ hybridization, respectively. Furthermore, almost
      all cases exhibited fluorescence after immunofluorescence staining with
      monoclonal anti-EBNA2 and anti-BZLF1 antibodies, and 15 cases were positive after
      treatment with monoclonal anti-LMP1 antibody. PCR-Southern blotting detected an
      amplified EBER1 sequence in all 9 cases examined. EBV expression was confirmed in
      LCH using in situ hybridization and immunofluorescence. Furthermore, EBV DNA was
      also detected by PCR-Southern blotting. These positive results of BZLF1 suggest
      that EBV replicates in LCH tissues.

PMID- 15257552
TI  - Placental fetal thrombotic vasculopathy is associated with neonatal
      encephalopathy.
AB  - Neonatal encephalopathy (NE) remains an important cause of morbidity and
      mortality in the term infant, and many cases have an antepartum, rather than an
      intrapartum, etiology. Chronic processes such as thrombosis result in changes in
      the placenta. We sought to determine whether histopathological examination of the
      placenta in cases of NE, focusing on these changes, could identify significant
      antenatal processes that are not recognized by clinical assessment alone. Infants
      born at term with NE were identified retrospectively over a 12-year period.
      Placental tissue from deliveries during the study period was available for
      reexamination. Controls were selected from a cohort of 1000 consecutive
      deliveries on which clinical and pathological data were collected as part of an
      earlier study. Bivariate and multivariate analyses of clinical and pathological
      factors for cases and controls were used to test for an independent association
      with NE. Clinical and placental data was collected on 93 cases of NE and 387
      controls. The placental features of fetal thrombotic vasculopathy (FTV),
      funisitis (signifying a fetal response to infection), and accelerated villous
      maturation were independently associated with NE. Of the clinical factors
      studied, meconium-stained liquor and abnormal cardiotocograph were independently
      associated. There were no independently associated clinical antenatal factors.
      Placental features of infection, thrombosis, and disturbed uteroplacental flow
      are significant independent factors in the etiology of NE in this study. Acute
      and chronic features suggest that NE may result from acute stress in an already
      compromised infant. The absence of significant clinical antenatal factors
      supports the value of placental examination in the investigation of infants with
      NE.

PMID- 15257551
TI  - Biotin-rich, optically clear nuclei express estrogen receptor-beta: tumors with
      morules may develop under the influence of estrogen and aberrant beta-catenin
      expression.
AB  - Recent studies have indicated that aberrant beta-catenin expression may be a
      common denominator for the morular formation of tumors from various anatomic
      sites. The evidence for the influence of female sex hormones in the formation of
      morules has been circumstantial, most previous studies having failed to
      demonstrate female sex hormone receptors in the morular cells. We investigated a
      possible role of estrogen receptor (ER)-beta in the occurrence of tumors that
      form morules with biotin-rich optically clear nuclei (BROCN)(BROCN-family tumors)
      and its possible relationship with aberrant nuclear/cytoplasmic (N/C) beta
      catenin expression. We immunostained 14 BROCN-family tumors, including 6 low
      grade adenocarcinomas of the fetal lung type, 3 papillary thyroid carcinomas of
      cribriform-morular variant (CMV), 2 ovarian endometrioid tumors, 2 colonic
      adenocarcinomas, and 1 gallbladder adenoma, as well as 4 cases of endometrial
      tissue with BROCN during gestation, for ERbeta, ERalpha, progesterone receptor
      (PgR), beta-catenin, and, on a subset of cases, c-Fos and MIB-1 as well. BROCN in
      all 18 cases expressed ERbeta but not ERalpha or PgR. In the BROCN-family tumors,
      the morular cells and budding glandular cells expressed ERbeta in the cytoplasm
      and BROCN, which overlapped with the N/C expression pattern of beta-catenin. Beta
      catenin showed only membranous expression in the endometrial glands during
      gestation. In CMV and ovarian endometrioid tumors, nuclear expression of ERalpha
      and PgR were observed in association with N/C beta-catenin expression only in the
      glandular component. C-Fos was also constantly and strongly expressed in BROCN in
      all cases examined. The MIB-1 labeling index was low in the morular area, ranging
      from 1% to 3%. The present study indicates that N/C co-localization of ERbeta and
      beta-catenin is a feature common to the morules with BROCN that appear in the
      BROCN-family tumors from various anatomic sites. Whether the estrogen-signaling
      pathway and the Wnt-signaling pathway have crosstalk, cooperating in the
      development of the BROCN-family tumors, awaits further study.

PMID- 15257553
TI  - Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular
      carcinoma.
AB  - Although dendritic cells (DCs) play an important role in tumor immunity, there
      have been no reports on their role in cholangiocellular carcinoma (CCC). In 26
      formalin-fixed, paraffin-embedded tissue sections from patients with CCC, cells
      positive for CD83 (a marker of mature DCs), CD1a (a marker of immature DCs), and
      CD8 and CD4 (T cell markers) were counted, and expression of glucose-regulated
      protein (grp) 94, which is considered to participate in the maturation of DCs,
      was evaluated by immunohistochemistry and Western blot analysis to study the
      relationship between their expression and patients' disease outcome. The number
      of CD83-positive DCs at the invasive margin of CCCs correlated significantly with
      the number of CD8-positive or CD4-positive T cells in the cancerous region and
      was significantly higher in grp94-positive cancer than in grp94-negative cancer
      (P = 0.0006). CD83-positive patients (positive cells in invasive margin >
      12.4/field) had both a significantly lower incidence of lymph node metastasis
      (23.1% vs 69.2%; P = 0.0206) and a better outcome than CD83-negative patients (P
      <0.001). We conclude that mature DCs are distributed predominantly at the
      invasive margin of cancers, and a significantly higher number of mature DCs at
      the invasive margin are observed in patients with grp94-positive cancer cells.
      Mature DCs may enhance CD8- and CD4-positive cell infiltration into cancers and
      improve prognosis in patients with CCC, due in part to abatement of lymph node
      metastasis.

PMID- 15257554
TI  - Comparison of DNA ploidy status and DNA ploidy-related parameters in malignant
      melanoma tissue microarrays and full sections.
AB  - A new high-throughput tissue-arraying technique, now frequently used in tumor
      pathology, requires standardization of methods of DNA analysis, previously
      applied in full histological sections. The main objectives of this study were to
      evaluate DNA ploidy status and DNA ploidy-related parameters using the CAS200
      image analyzer in malignant melanoma tissue microarrays and to compare them with
      full histological sections. Comparison of DNA ploidy-related parameters,
      including percentage of diploid cells, percentage of aneuploid cells between 2c
      and 4c, percentage of tetraploid cells, percentage of aneuploid cells between 4c
      and 8c, percentage of octaploid cells, percentage of 16-ploid cells, and 5c
      exceeding rate, did not reveal any significant differences between malignant
      melanoma tissue microarrays and full sections. The DNA ploidy status according to
      Auer differed in 1 out of 59 cases investigated. Our study demonstrated that it
      is possible to evaluate DNA ploidy status and DNA ploidy-related parameters in
      tissue microarrays, which is of practical relevance to tumor pathology.

PMID- 15257555
TI  - Interstitial granulomatous dermatitis with arthritis.
AB  - Interstitial granulomatous dermatitis with arthritis is an uncommon disorder. In
      its original description, the presence of linear inflammatory indurations on the
      lateral aspects of the trunk (the rope sign) in association with arthritis were
      considered the pathognomonic clinical features. Later cases presenting with
      plaques and papules have been reported. Herein we describe a case of interstitial
      granulomatous dermatitis with arthritis without the rope sign. The present case
      supports the idea that interstitial granulomatous dermatitis with arthritis may
      have variable clinical appearances.

PMID- 15257556
TI  - Acute liver failure in a renal transplant patient caused by adenoviral hepatitis
      superimposed on a fibrosing cholestatic hepatitis B.
AB  - We report the first case of fulminant liver failure due to necrotizing adenovirus
      hepatitis superimposed on a fibrosing cholestatic hepatitis B in an
      immunosuppressed patient after renal transplantation. Diagnosis was made in vivo
      by liver biopsy and confirmed at autopsy.

PMID- 15257557
TI  - Intestinal pseudotumorous gouty nodulosis: a colonic tophus without manifestation
      of gouty arthritis.
AB  - A 37-year-old black woman with nephritis secondary to systemic lupus
      erythematosus, steroid-induced diabetes mellitus, and hypertension presented with
      fever, nausea, vomiting, and right upper quadrant abdominal pain with distension.
      Abdominal computed tomography (CT) scan revealed a colonic mass, and CT- guided
      fine-needle aspiration demonstrated birefringent crystalline material. After
      several weeks of antibiotic therapy, the patient underwent laparoscopic
      examination followed by extended right hemicolectomy for a large mass in the
      subserosa of the transverse colon. Pathological examination of this mass revealed
      it to be a gouty tophus. To our knowledge, no case of tophaceous gout presenting
      as an intestinal mass has previously been reported.

PMID- 15257558
TI  - Transformation of diffuse large B-cell lymphoma into pre-B acute lymphoblastic
      leukemia: clinicopathologic features and clonal relationship.
AB  - A patient with fibrosing alveolitis developed a diffuse large B-cell (DLBC)
      lymphoma that expressed CD20 and CD30. After an initial response, the lymphoma
      relapsed and was salvaged with further chemotherapy. After another remission of 3
      years, a pre-B-cell acute lymphoblastic leukemia (ALL), which expressed CD10,
      CD19, CD22, CD79a, CD34 and terminal deoxyribonucleotidyl transferase, developed
      and led to death. Molecular analysis of the immunoglobulin heavy-chain gene
      showed that the initial lymphoma and its relapse were clonally related. At
      leukemic relapse, 2 clones related to the initial and relapsed lymphoma clones
      were present. DLBC lymphomas arise from post-follicle center B cells, whereas ALL
      arises from pregerminal B cells. Therefore, a direct transformation of DLBC
      lymphoma to ALL appears unlikely. The overall features suggest instead separate
      lymphoma and leukemic evolution from a common mutated B-cell precursor rather
      than transformation of DLBC lymphoma to ALL.

PMID- 15257559
TI  - Her-2 testing: the numbers just don't add up.

PMID- 15257560
TI  - Diagnostic accuracy of second-opinion diagnoses based on still images.

PMID- 15257561
TI  - Modelling cellular and tissue function. Proceedings of a conference. July, 2003.
      Auckland, New Zealand.

PMID- 15257562
TI  - Proceedings of the Centenary Symposium to Celebrate the Discovery of Schistosoma
      japonicum. Part 2. March 31, 2003. Kurume, Japan.

PMID- 15257563
TI  - C-reactive protein and coronary heart disease.

PMID- 15257564
TI  - C-reactive protein and coronary heart disease.

PMID- 15257565
TI  - C-reactive protein and coronary heart disease.

PMID- 15257566
TI  - Bioethics, science, and politics.

PMID- 15257567
TI  - Bioethics, science, and politics.

PMID- 15257568
TI  - Bioethics, science, and politics.

PMID- 15257569
TI  - Management of cirrhosis and ascites.

PMID- 15257570
TI  - My pseudoscientific nightmare.

PMID- 15257571
TI  - Structural and functional analogue of the active site of polysulfide reductase
      from Wolinella succinogenes.
AB  - Synthesis of [PPh4]2[Mo(SPh)2(S2C2(CN)2)2] (2) from [PPh4]2[MoO(S2C2(CN)2)2] (1)
      has been achieved to mimic the postulated [Mo(S)6] core of polysulfide reductase
      with two thiolates and two bis(ene-dithiolate) ligands. Compound 2 reacts with
      polysulfide to yield H2S, modeling the function of polysulfide reductase. The
      facile conversion of 2 back to 1 in moist solvent suggests that the
      interconversion of the [MoIV = O] and [MoIV - X] (X = O-Ser, S-Cys, Se-Cys)
      moieties might occur in the DMSO reductase class of enzymes under appropriate
      hydrophobic/hydrophilic conditions.

PMID- 15257572
TI  - Structure and magnetic properties of the ferromagnetic Cu3Cl12(6)- trimer in
      [(NH3C2H4)3NH]2Cu3Cl14.
AB  - The crystal structure consists of a strongly hydrogen bonded network of tris(N
      ethylammonium)ammonium cations, Cu3Cl12(6)- trimeric species, and Cl- anions. The
      Cu3Cl12(6)- trimers are formed by two distorted tetrahedral CuCl4(2)- anions
      linked to a central square planar CuCl4(2)- anion via semicoordinate Cu-Cl...Cu
      mu1 bridges. The central copper ion shows only small deviations from ideal D4h
      symmetry, while the terminal copper ions show a mild distortion from D2d symmetry
      with an average trans Cl-Cu-Cl angle of 136.0 degrees. The semicoordinate
      linkages provide a ferromagnetic exchange pathway between the copper ions with
      J/k = 6.91(3) K. Short Cl...Cl contacts (3.67-3.90 angstoms) lead to very weak
      antiferromagnetic coupling between the ferromagnetically coupled trimers.

PMID- 15257573
TI  - Layered organic-based metal iodide-polyiodide with unique mixed-valent
      gold(I/III) iodide chains.
AB  - We report the synthesis, optical spectrum, and crystal and electronic structures
      of a new organic-inorganic hybrid compound, [(p-NH3C6H4)2CH2]4
      [(AuI2)(AuI4)(I2)2(I5)2Cl4], with unique mixed-valent gold(I/III) chains. The
      chains feature face-shared octahedral [AuIAu(III)I6]2- units and are embedded
      within polyiodide layers. The new mixed-valent gold iodide crystallizes in the
      orthorhombic space group Pnnm, with a = 27.0703(2), b = 8.9363(5), c = 18.4280(1)
      angstroms, Z = 2, and exhibits an optical band gap of 0.53 eV.

PMID- 15257574
TI  - Self-assembly of high-nuclearity metal clusters: programmed expansion of a
      metallasiloxane cage to an octacopper(II) cluster.
AB  - The novel octanuclear copper(II) cluster
      [Cu6[(PhSiO2)6]2[NCCu(Me6tren)]2(MeOH)4]2+ (1) has been isolated as a perchlorate
      salt by reacting the hexacopper(II) metallasiloxane cage
      [Cu6[(PhSiO2)6]2(nBuOH)x] (x = 4, 6) with [Cu(Me6tren)CN]ClO4 in a
      methanol/chloroform mixture (Me6tren = tris(2-(dimethylamino)ethyl) amine).
      Crystal data for 1(ClO4)2 x MeOH: monoclinic, space group P2(1)/n (no. 14), a =
      16.8490(3) angstroms, b = 22.2966(4) angstroms, c = 17.2508(3) angstroms, beta =
      94.7658(5) degrees, V = 6458.3(2) angstroms3, Z = 2. The structure comprises a
      highly distorted hexagonal Cu6 array linked to two [Cu(Me6tren)] units via
      cyanide bridges. Magnetic measurements reveal that the addition of the copper
      cyanide complexes dramatically affects the magnetism of the Cu6 unit, whose
      ground spin state changes from S = 3 to S = 0.

PMID- 15257575
TI  - Hydrothermal route to InAs semiconductor nanocrystals.
AB  - Spherical InAs nanocrystals of 30-50 nm were hydrothermally synthesized at 120
      degrees C, which showed a 100 meV-blueshift of band gap absorption and phonon
      confinement of optical vibration mode. The study of hydrothermal formation
      mechanism indicated that crystalline InAs could be obtained in an extended pH
      range (approximately -0.15 to 14).

PMID- 15257576
TI  - Chelating of titanium by lactic acid in the water-soluble diammonium tris(2
      hydroxypropionato)titanate(IV).
AB  - Stable water-soluble diammonium tris(2-hydroxypropionato)titanate(IV) [ammonium
      trilactatotitanate(IV)], (NH4)2[Ti(C3H4O3)3], was prepared in the crystalline
      form. According to the X-ray single-crystal diffraction data, this compound
      crystallizes in the cubic cell with a = 11.649(4) angstroms, space group P2(1)3
      (no. 198), and has Z = 4 molecules per unit cell. The 13C NMR data and Raman and
      IR spectra support the determined structure. The absence of nonbonded functional
      groups restricts the formation of oligomers in contrast to the reported
      speciation of citratoperoxotitanate(IV) complexes.

PMID- 15257577
TI  - An unusual 3D coordination polymer based on bridging interactions of the
      nucleobase adenine.
AB  - The first 3D coordination polymer containing a nucleobase as a bridging ligand,
      [[Cu2(mu-ade)4(H2O)2][Cu(ox)(H2O)]2 x approximately 14H2O]n (1), has been
      synthesized by reaction of adenine (Hade) with a basic solution of K2[Cu(ox)2] x
      2H2O (ox = oxalato dianion). Compound 1 crystallizes in the trigonal space group
      R3 with a = b = 31.350(1) angstroms, c = 14.285(1) angstroms, V = 12158.7(10)
      angstroms3, and Z = 9. X-ray analysis shows a covalent 3D network in which the
      copper(II) centers are bridged by tridentate mu-N3,N7,N9 adeninate ligands. The
      compound has relatively large, nanometer-sized tubes associated with the self
      assembly process directed solely by metal-ligand interactions. The covalent 3D
      framework remains intact upon removal of the guest water molecules trapped in the
      nanotubes. Magnetic measurements indicate an overall antiferromagnetic behavior
      of the compound.

PMID- 15257578
TI  - [CoAu2(CN)4(NITpPy)2(H2O)2]n: a new 2-D interdigitating complex containing
      dicyanoaurate(I) anion, a radical, and cobalt(II) ion incorporating gold...gold
      and hydrogen bonding interactions.
AB  - A novel complex, [[CoAu2(CN)4(NITpPy)2(H2O)2]]n, 1, containing the cobalt(II)
      ion, dicyanoaurate(I) anion, and nitronyl nitroxide radical building blocks, has
      been prepared and structurally characterized by single-crystal X-ray analysis.
      The structure of complex 1 illustrates that aurophilicity and hydrogen bonding
      interactions increase dimensionality, generating a 2-D interdigitating system.
      The spectroscopic and magnetic properties have been investigated.

PMID- 15257579
TI  - 7Li PGSE diffusion measurements on LiPPh2: a solvent dependence of the structure.
AB  - The first application of 7Li pulsed-gradient spin-echo (PGSE) diffusion methods
      to structural lithium chemistry is reported. The data, which provide quantitative
      diffusion constants at 155 K, lead to a new method of estimating solvent
      viscosity at this temperature and clearly show a solvent dependence for the
      structure of LiPPh2. In THF, LiPPh2 exists as a mononuclear solvated species,
      whereas in Et2O, a dinuclear structure is found. D values for the model compound
      PHPh2 in THF have been measured.

PMID- 15257580
TI  - Dicopper-dioxygen complex supported by asymmetric pentapyridine dinucleating
      ligand.
AB  - A dicopper(I) complex supported by a novel asymmetric pentapyridine dinucleating
      ligand, consisting of tetradentate and tridentate metal-binding sites, has been
      synthesized and characterized. The dicopper(I) complex reacted with molecular
      oxygen at a low temperature to give an unprecedented mu-peroxo dicopper(II)
      complex presumably having a mu-eta1:eta2 binding mode, the spectroscopic features
      and the reactivity of which have been explored in detail.

PMID- 15257581
TI  - Supramolecular and coordination polymer complexes supported by a tripodal
      tripyridine ligand containing a 1,3,5-triethylbenzene spacer.
AB  - By By combining a tripodal tripyridine ligand containing a 1,3,5-triethylbenzene
      spacer (L) with several divalent transition-metal chlorides, we have selectively
      prepared a capsule-type supramolecular complex, [PdII3(L)2Cl6] x 2H2O, and one
      dimensional (1D) coordination polymer complexes, ([CuII(L)Cl2] x C2H5OH)n,
      ([CoII3(L)2Cl6] x 2CH2Cl2)n, and ([ZnII3(L)2Cl6] x 2H2O)n, with a zigzag polymer
      chain, a linear polymer chain, and a ladder polymer chain structure,
      respectively. All the structures were established in detail by single-crystal X
      ray diffraction analysis, and the factors inducing the structural differences
      among the complexes are discussed by taking account of the differences in
      coordination geometry (square planar vs tetrahedral) as well as metal-ligand
      binding strength in the complexes.

PMID- 15257582
TI  - Structure and bonding in the omnicapped truncated tetrahedral Au20 cluster:
      analogies between gold and carbon cluster chemistry.
AB  - The proposed omnicapped truncated tetrahedral structure of the recently reported
      Au20 cluster can be generated from a regular dodecahedron by forming two
      transannular Au-Au bonds across each face while preserving T symmetry. An
      electron-precise chemical bonding scheme accounts for the large band gap (1.77
      eV) of Au20 and relates its structure to that of titanacarbohedrene Ti8C12 and
      Os20(CO)40(2)-.

PMID- 15257583
TI  - Triethanolamine zinc phosphite, (C6H13NO3)Zn2(HPO3): a templated network or a
      network of clusters?
AB  - (C6H13NO3)Zn2(HPO3) (I) displays an extended hybrid organic/inorganic structure
      in which the triethanolamine organic species acts as an anionic tetradentate
      ligand, rather than a typical protonated cationic template. Crystal data for I:
      Mr = 357.89, monoclinic, P2(1)/c (no. 14), a = 8.4216(4) angstroms, b = 9.9262(5)
      angstroms, c = 12.8494(6) angstroms, beta = 91.824(1) degrees, V = 1073.6(1)
      angstroms3, Z = 4.

PMID- 15257584
TI  - [Ru(bpy)2(L)]Cl2: luminescent metal complexes that bind DNA base mismatches.
AB  - Here we report the synthesis of luminescent ruthenium complexes that bind DNA
      base pair mismatches. [Ru(bpy)2(tpqp)]Cl2 (tpqp = 7,8,13,14-tetrahydro-6
      phenylquino[8,7-k][1,8]phenanthroline), [Ru(bpy)2(pqp)]Cl2 (pqp = 6
      phenylquino[8,7-k][1,8]phenanthroline), and [Ru(bpy)2(tactp)]Cl2 [tactp =
      4,5,9,18-tetraazachryseno[9,10-b]triphenylene] have been synthesized, and their
      spectroscopic properties in the absence and presence of DNA have been examined.
      While [Ru(bpy)2(pqp)]2+ shows no detectable luminescence, [Ru(bpy)2(tpqp)]2+ is
      luminescent in the absence and presence of DNA with an excited-state lifetime of
      10 ns and a quantum yield of 0.002. Although no increase in emission intensity is
      associated with binding to mismatch-containing DNA, luminescence quenching
      experiments and measurements of steady-state fluorescence polarization provide
      evidence for preferential binding to oligonucleotides containing a CC mismatch.
      Furthermore, by marking the site of binding through singlet oxygen sensitized
      damage, the complex has been shown to target a CC mismatch site directly with a
      specific binding affinity, Kb = 4 x 10(6) M(-1). [Ru(bpy)2(tactp)]2+, an analogue
      of [Ru(bpy)2(dppz)]2+ containing a bulky intercalating ligand, is luminescent in
      aqueous solution at micromolar concentrations and exhibits a 12-fold enhancement
      in luminescence in the presence of DNA. The complex, however, tends to aggregate
      in aqueous solution; we find a dimerization constant of 9.8 x 10(5) M(-1). Again,
      by singlet oxygen sensitization it is apparent that [Ru(bpy)2(tactp)]2+ binds
      preferentially to a CC mismatch; using a DNase I footprinting assay, a binding
      constant to a CC mismatch of 8 x 10(5) M(-1) is found. Hence results with these
      novel luminescent complexes support the concept of using a structurally demanding
      ligand to obtain selectivity in targeting single base mismatches in DNA. The
      challenge is coupling the differential binding we can obtain to differential
      luminescence.

PMID- 15257585
TI  - Determination by X-ray absorption spectroscopy of the Fe-Fe separation in the
      oxidized form of the hydroxylase of methane monooxygenase alone and in the
      presence of MMOD.
AB  - The diiron active site in the hydroxylase of Methylococcus capsulatus (Bath)
      methane monooxygenase (MMOH) has been studied in the oxidized form by X-ray
      absorption spectroscopy (XAS). Previous investigations by XAS and X-ray
      crystallography have identified two different distances (3.0 and 3.4 angstroms)
      between the two Fe atoms in the dinuclear site. The present study has employed a
      systematic extended X-ray absorption fine structure (EXAFS) fitting methodology,
      utilizing known and simulated active site and relevant model structures, to
      determine unambiguously the Fe-Fe separation in the oxidized form of MMOH.
      Consistent and unique fits were only possible for an Fe-Fe distance of 3.0
      angstroms. This methodology was then applied to study potential changes in the
      active site local structure in the presence of MMOD, a protein of unknown
      function in multicomponent MMO. Fe K-edge and EXAFS analyses revealed negligible
      changes in the diiron site electronic and geometric structure upon addition of
      MMOD to oxidized MMOH.

PMID- 15257586
TI  - An unprecedented trinuclear structure involving two high-spin and one spin
      crossover iron(II) centers.
AB  - Anaerobic reaction of ferrous thiocyanate with the deprotonated form of the
      pentadentate dinucleating Schiff base 1,3-bis[(2-pyridylmethyl)imino]propan-2-ol
      (LH) yields the novel trinuclear [Fe3L2(NCS)4(H2O)] species 1. LH results from
      the bis-condensation of 2-acetyl-pyridine with 1,3-diaminopropan-2-ol and
      includes an N4O donor set. The X-ray crystal structure of 1 [C38H40N12O3S4Fe3,
      triclinic, space group P-1; a = 10.7730(10) angstroms, b = 12.2048(14) angstroms,
      c = 19.0559(19) angstroms, alpha = 76.908(12) degrees, beta = 89.106(12) degrees,
      gamma = 79.637(12) degrees, V = 2399.8(4) angstroms3] can be described either as
      a bent linear arrangement of ferrous centers pairwise bridged through the alkoxo
      oxygen atom of L- or as a triangular FeII3 core with an Fe2-SCN-Fe3 bridge as the
      longer side of the Fe1-Fe2-Fe3 triangle. The metric parameters characterizing the
      ligand environments of the three ferrous centers in 1 and its Mossbauer spectra
      show that this unprecedented trinuclear structure involves two high-spin (Fe2 and
      Fe3) and one spin-crossover (Fe1) FeII centers. The donor set to the spin
      crossover center (Fe1) is unprecedented: two Npyridine, two Nimine, and two
      Oalkoxo. Weak antiferromagnetic interactions transmitted through the end-to-end
      NCS bridge and/or through the O1-Fe1-O2 bridge operate between Fe2 and Fe3.

PMID- 15257587
TI  - Syntheses of the 47 electron clusters [(Cp*Fe)3(mu3-X)2] (X = S, Se) and the
      First Fe/Sn/Se Heterocubane Cluster [(CpFe)3(SnCl3)(mu3-Se)4] x DME by the use of
      chalcogenostannate salts.
AB  - By reacting 1-aminoethylammonium (H2NCH2CH2NH3+ = enH+) salts of [Sn2E6]4- anions
      (E = S, Se), [enH]4[Sn2S6] (1) and [enH]4[Sn2Se6] x en (2), with FeCl2/LiCp,
      three novel (partly) oxidized, Cp* ligated iron chalcogenide clusters were
      synthesized. Two of them, [(CpFe)3(mu3-S)2] (3) and [(Cp*Fe)3(mu3-Se)2] (4),
      contain formally 47 valence electrons. [(Cp*Fe)3(SnCl3)(mu3-Se)4] x DME (5)
      represents the first known mixed metal Fe/Sn/Se heterocubane type cluster.
      Compounds 3-5 were structurally characterized by single-crystal X-ray
      diffraction, and the odd valence electron number of the [Fe3E2] clusters (E = S,
      Se) was confirmed by density functional (DFT) investigations, mass spectrometry,
      cyclic voltammetry and a susceptibility measurement of 3.

PMID- 15257588
TI  - Composition-structure relationships in polar intermetallics: experimental and
      theoretical studies of LaNi(1 + x)Al(6 - x) (x = 0.44).
AB  - A new ternary aluminide, LaNi(1 + x)Al(6 - x ) (x = 0.44), has been synthesized
      from La, Ni, and Al in sealed silica tubes. Its structure, determined by single
      crystal X-ray diffraction, is tetragonal P4/mmm (No. 123) with Z = 1 and has the
      lattice parameters a = 4.200(8) and c = 8.080(8) angstroms. Refinement based on
      Fo2 yielded R1 = 0.0197 and wR2 = 0.020 [I > 2sigmaI]. The compound adopts a
      structure type previously observed in SrAu2Ga5 and EuAu2Ga5. The atomic
      arrangement is closely related to the one in BaAl4 as well as in other rare-earth
      gallide compounds such as LaNi0.6Ga6, HoCoGa5, Ce4Ni2Ga20, Ce4Ni2Ga17, Ce4NiGa18,
      and Ce3Ni2Ga15. This structure exhibits a large open cavity which may be filled
      by a guest atom. Band structure calculations using density functional theory have
      been carried out to understand the stability of this new compound.

PMID- 15257589
TI  - Hydrothermal synthesis and characterization of new pillared layered
      ethylenediphosphonates of molybdenum(VI), A2[Mo2O5(O3PCH2CH2PO3)] (A = NH4, Tl,
      Cs, Rb) and K(H3O)[Mo2O5(O3PCH2CH2PO3)].
AB  - New ethylenediphosphonates of molybdenum, A[Mo2O5(O3PCH2CH2PO3)] (A = NH4 (1), Tl
      (2), Cs (3), Rb (4)), and K(H3O)[Mo2O5(O3PCH2CH2PO3)] (5), have been synthesized
      by a hydrothermal method and structurally characterized by X-ray diffraction,
      spectroscopic, and thermal studies. These compounds consist of pillared anionic
      layers [Mo2O5(O3PCH2CH2PO3)]2-, with A+, K+, and H3O+ ions in the interlayer
      region as well as in the cavities within the anionic layers. Single-crystal X-ray
      structures of compounds 1 and 5 have been determined. They crystallize in the
      orthorhombic space group Cmca with Z = 8 and have the following unit cell
      parameters. For 1, a = 25.60(1), b = 10.016(4), and c = 9.635(3) angstroms and
      for 5, a = 25.63(1), b = 10.007(2), and c = 9.512(1) angstroms.

PMID- 15257590
TI  - Perovskite-like Metal Formates with Weak Ferromagnetism and as Precursors to
      Amorphous Materials.
AB  - Three isomorphous compounds M(CHOO)3[NH2(CH3)2] (M = Mn(1 x Mn), Co(2 x Co), Ni(3
      x Ni)) have been synthesized in solvothermal conditions. Single-crystal X-ray
      diffraction shows that they are all crystallized in the trigonal space group R c
      with small differences in the lattice parameters. Bridged by the three-atom
      single-bridge CHOO-, M ions form a three-dimensional distorted perovskite-like
      structure with dimethylamine (DMA) cations located in the cages of the network.
      Based on the magnetic data, these three 3D compounds are weak ferromagnets with
      the critical temperature Tc = 8.5 K (1 x Mn), 14.9 K (2 x Co), and 35.6 K (3 x
      Ni), and for 2 x Co and 3 x Ni, spin reorientation might take place at 13.1 and
      14.3 K, respectively. At 1.8 K, hysteresis loops can be observed for all three
      compounds with the coercivity field ca. 90 Oe (1 x Mn), 920 Oe (2 x Co), and 320
      Oe (3 x Ni). The canting angles are estimated to be 0.08 degrees, 0.5 degrees,
      and 0.6 degrees for 1 x Mn, 2 x Co, and 3.Ni, respectively. The magnetic coupling
      between MnII ions in 1.Mn was estimated based on the model developed by Rushbrook
      and Wood for a Heisenberg antiferromagnet on a simple cubic lattice and the best
      fit gives J = -0.23 cm(-1). At the same time, according to molecular field theory
      of antiferromagnetism, the J values for compounds 1 x Mn, 2 x Co, and 3 x Ni were
      estimated to be -0.32 cm(-1), -2.3 cm(-1), and -4.85 cm(-1), respectively. The
      spin cant in these compounds may originate from the noncentrosymmetric character
      of the three-atom single-bridge CHOO-. Furthermore, amorphous materials 4 x
      Mn238, 5 x Mn450, 6 x Co320, and 7 x Ni300 were prepared from precursors 1-3
      under an argon atmosphere at different temperatures according to the
      thermogravimetric analyses. As an interesting result, 5 x Mn450 was confirmed to
      be an amorphous form of Mn3O4 with a considerably large coercivity field HC = 4.1
      kOe at 30 K compared to that value (250 Oe) for bulk Mn3O4.

PMID- 15257591
TI  - Attachment of an electron-withdrawing fluorophore to a cryptand for modulation of
      fluorescence signaling.
AB  - The laterally nonsymmetric aza cryptand synthesized by condensing tris(2
      aminoethyl)amine (tren) with tris[2-[(3-(oxomethyl)phenyl)oxy]ethyl]mine readily
      forms mononuclear inclusion complexes with both transition- and main-group-metal
      ions. The fluorophore 7-nitrobenz-2-oxa-1,3-diazole is attached to one of the
      secondary amines, to give an integrated fluorophore-receptor configuration. The
      fluorophoric system does not show any appreciable emission when excited due to an
      efficient photoinduced intramolecular electron transfer (PET) from the nitrogen
      lone pair. When a metal ion enters the cavity, the PET is blocked, causing
      recovery of fluorescence; Cd(II) gives the highest quantum yield. The
      fluorophore, with pi-accepting ability, drastically alters the binding property
      of the cryptand. With perchlorate or tetrafluoroborate salts of Cd(II), the metal
      ion enters the cavity, causing recovery of fluorescence. However, in the presence
      of coordinating ions such as Cl-, N3-, and SCN-, the metal ion comes out of the
      cavity, causing PET to take place once again, and the fluorescence is lost. Thus,
      translocation of Cd(II) between the inside and outside of the cryptand cavity can
      lead to a reversible fluorescence on/off situation.

PMID- 15257592
TI  - Two polymorphs of cobalt(II) imidazolate polymers synthesized solvothermally by
      using one organic template N,N-dimethylacetamide.
AB  - Two structurally different polymorphs of cobalt(II) imidazolate frameworks are
      solvothermally synthesized by using N,N-dimethylacetamide as a template: The
      polymorph 6 (a = 9.797 (4) angstroms, b = 15.301(6) angstroms, c =14.902(6)
      angstroms, beta = 98.904(6) degrees, monoclinic, P21/n) shows structures of
      silicate CaAl2Si2O8 with CrB4 topology, while polymorph 7 (a = 15.173(4)
      angstroms, b = 15.173(4) angstroms, c = 19.089(5) angstroms, Pbca) shows CaGa2O4
      related topological structures. In addition, the 7' (a = 15.9712(18) angstroms, b
      = 15.9253(19) angstroms, c = 18.475(2) angstroms, Pbca), a compound isostructural
      with 7, is synthesized by using cyclohexanol as a template. Thus, these
      cobalt(II) imidazolate polymers are reminiscent of the zeolite syntheses in that
      not only the same topological structure can be synthesized by using the different
      organic templates, but also different topological structures can be synthesized
      by using the same organic template.

PMID- 15257593
TI  - Preparation and characterization of 6-molybdocobaltate and 6-molybdoaluminate
      cobalt salts. Evidence of a new heteropolymolybdate structure.
AB  - Molybdenum and cobalt based heteropolyanions (HPAs) could be used as an
      alternative to the conventional ammonium heptamolybdate and cobalt nitrate
      starting materials for friendly environmental preparation of Co-Mo/Al2O3
      hydrotreating catalysts. In this aim, cobalt salts of molybdocobaltate and
      molydboaluminate Anderson HPAs have been synthesized and characterized by TGA,
      XRD, XAS, and vibrational spectroscopies. The crystal structure refinement
      provided evidence for the formation of a new heteropolyoxomolybdate derived from
      the well-known Anderson structure.

PMID- 15257594
TI  - The coordination chemistry of "[BP3]NiX" platforms: targeting low-valent nickel
      sources as promising candidates to L3Ni=E and L3Ni(triple bond)E linkages.
AB  - A series of divalent, monovalent, and zerovalent nickel complexes supported by
      the electron-releasing, monoanionic tris(phosphino)borate ligands [PhBP3] and
      [PhBPiPr3] ([PhBP3] = [PhB(CH2PPh2)3]-, [PhBPiPr3] = [PhB(CH2PiPr2)3]-) have been
      synthesized to explore fundamental aspects of their coordination chemistry. The
      pseudotetrahedral, divalent halide complexes [PhBP3]NiCl (1), [PhBP3]NiI (2), and
      [PhBPiPr3]NiCl (3) were prepared by the metalation of [PhBP3]Tl or [PhBPiPr3]Tl
      with (Ph3P)2NiCl2, NiI2, and (DME)NiCl2 (DME = 1,2-dimethoxyethane),
      respectively. Complex 1 is a versatile precursor to a series of complexes
      accessible via substitution reactions including [PhBP3]Ni(N3) (4),
      [PhBP3]Ni(OSiPh3) (5), [PhBP3]Ni(O-p-tBu-Ph) (6), and [PhBP3]Ni(S-p-tBu-Ph) (7).
      Complexes 2-5 and 7 have been characterized by X-ray diffraction (XRD) and are
      pseudotetrahedral monomers in the solid state. Complex 1 reacts readily with
      oxygen to form the four-electron-oxidation product,
      [[PhB(CH2POPh2)2(CH2PPh2)]NiCl] (8A or 8B), which features a solid-state
      structure that is dependent on its method of crystallization. Chemical reduction
      of 1 using Na/Hg or other potential 1-electron reductants generates a product
      that arises from partial ligand degradation, [PhBP3]Ni(eta2-CH2PPh2) (9). The
      more sterically hindered chloride 3 reacts with Li(dbabh) (Hdbabh = 2,3:5,6
      dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene) to provide the three-coordinate
      complex [kappa2-PhBPiPr3]Ni(dbabh) (11), also characterized by XRD. Chemical
      reduction of complex 1 in the presence of L-type donors produces the tetrahedral
      Ni(I) complexes [PhBP3]Ni(PPh3) (12) and [PhBP3]Ni(CNtBu) (13). Reduction of 3
      following the addition of PMe3 or tert-butyl isocyanide affords the Ni(I)
      complexes [PhBPiPr3]Ni(PMe3) (14) and [PhBPiPr3]Ni(CNtBu) (15), respectively. The
      reactivity of these [PhBP3]NiIL and [PhBPiPr3]NiIL complexes with respect to
      oxidative group transfer reactions from organic azides and diazoalkanes is
      discussed. The zerovalent nitrosyl complex [PhBP3]Ni(NO) (16) is prepared by the
      reaction of 1 with excess NO or by treating 12 with stoichiometric NO. The
      anionic Ni(0) complexes [[kappa2-PhBP3]Ni(CO)2][nBu4N] (17) and [[kappa2
      PhBPiPr3]Ni(CO)2][ASN] (18) (ASN = 5-azoniaspiro[4.4]nonane) have been prepared
      by reacting [PhBP3]Tl or [PhBPiPr3]Tl with (Ph3P)2Ni(CO)2 in the presence of
      R4NBr. The photolysis of 17 appears to generate a new species consistent with a
      zerovalent monocarbonyl complex which we tentatively assign as
      [[PhBP3]Ni(CO)][nBu4N], although complete characterization of this complex has
      been difficult. Finally, theoretical DFT calculations are presented for the
      hypothetical low spin complexes [PhBP3]Ni(NtBu), [PhBPiPr3]Ni(NtBu),
      [PhBPiPr3]Ni(NMe), and [PhBPiPr3]Ni(N) to consider what role electronic structure
      factors might play with respect to the relative stability of these species.

PMID- 15257595
TI  - The activation of tertiary carboxamides in metal complexes: an experimental and
      theoretical study on the methanolysis of acylated bispicolylamine copper(II)
      complexes.
AB  - It is a well-established concept that the C-N bond cleavage of carboxamide
      functions is facilitated by the coordination of a metal ion to the carbonyl
      oxygen atom. In contrast, the alternative C-N bond activation by coordination of
      a neutral tertiary carboxamide nitrogen atom has not been studied. We present the
      first results on the effect of nitrogen pyramidalization in N-coordinated metal
      complexes on the methanolysis of tertiary carboxamide groups. An analysis of the
      reactions products obtained from the methanol cleavage of [(N-Acyl-bpa)Cu]2+ (bpa
      = N,N-bispicolylamine) complexes is presented together with experimental and high
      level theoretically calculated structures. The strong effect of different anions
      on the amide pyramidalization and subsequent C-N-bond cleavage is evaluated. We
      show that dichloro complexes [(N-Acyl-bpa)CuCl2] have much less activated amide
      groups than the corresponding triflate species. They should therefore be less
      reactive. However, [(N-Acyl-bpa)CuCl2] complexes dissociate in solution to give
      cationic monochloro complexes [(N-Acyl-bpa)Cu(S)Cl]+ (S = solvent molecule).
      Theoretical calculations show that the amide pyramidalization in the monochloro
      complexes is equal to that in the corresponding CF3SO3- salts. Consequently,
      chloro and triflato complexes are cleaved with similar rates and efficiencies.
      Parallels to and differences in the reactivity of purely organic distorted amides
      are discussed.

PMID- 15257596
TI  - Cobalt chemistry with mixed aminotroponiminate salicylaldiminate ligands:
      synthesis, characterization, and nitric oxide reactivity.
AB  - A new class of mixed aminotroponimine salicylaldimine ligands and their
      corresponding cobalt(II) complexes are reported. This work expands the family of
      cobalt(II) aminotroponiminato complexes to include salicylaldiminate and
      derivatized fluorescein moieties. The H2iPrSATI-n (n = 3, 4) ligands 3 and 4,
      respectively, contain an aminotroponimine moiety and a salicylaldimine fragment
      connected with an alkyl linker. In the H2iPrFATI-n (n = 3, 4) ligands 5 and 6, a
      derivatized fluorescein replaces the salicylaldimine fragment. The cobalt(II)
      complexes [Co(iPrSATI-3)] (7) and [Co2(iPrSATI-4)(2)] (9) were prepared and
      structurally characterized. The reaction of NO with both complexes ultimately
      results in the formation of a dinitrogen-containing species. The mononitrosyl,
      [Co(iPrSATI-3)(NO)] (8), was isolated and characterized. The reactivity of
      [Co(iPrFATI-3)] (10) and [Co(iPrFATI-4)] (11) with NO mimics that observed for
      the salicylaldimine derivatives, as monitored by solution IR spectroscopy. When
      followed by fluorescence spectroscopy, reaction of 11 with NO evoked a 3-fold
      increase in emission intensity after 22 h.

PMID- 15257597
TI  - Model of the iron hydrogenase active site covalently linked to a ruthenium
      photosensitizer: synthesis and photophysical properties.
AB  - A model of the iron hydrogenase active site with the structure [(mu-ADT)Fe2(CO)6]
      (ADT = azadithiolate (S-CH2-NR-CH2-S), (2: R = 4-bromophenyl, 3: R = 4
      iodophenyl)) has been assembled and covalently linked to a [Ru(terpy)2]2+
      photosensitizer. This trinuclear complex 1 represents one synthetic step toward
      the realization of our concept of light-driven proton reduction. A rigid
      phenylacetylene tether has been incorporated as the linking unit in 1 in order to
      prolong the lifetime of the otherwise short-lived [Ru(terpy)2]2+ excited state.
      The success of this strategy is demonstrated by comparison of the photophysical
      properties of 1 and of two related ruthenium complexes bearing acetylenic
      terpyridine ligands, with those of [Ru(terpy)2]2+. IR and electrochemical studies
      reveal that the nitrogen heteroatom of the ADT bridge has a marked influence on
      the electronic properties of the [Fe2(CO)6] core. Using the Rehm-Weller equation,
      the driving force for an electron transfer from the photoexcited *[Ru(terpy)2]2+
      to the diiron site in 1 was calculated to be uphill by 0.59 eV. During the
      construction of the trinuclear complex 1, n-propylamine has been identified as a
      decarbonylation agent on the [(mu-ADT)Fe2(CO)6] portion of the supermolecule.
      Following this procedure, the first azadithiolate-bridged dinuclear iron complex
      coordinated by a phosphine ligand [(mu-ADT)Fe2(CO)5PPh3] (4, R = 4-bromophenyl)
      was synthesized.

PMID- 15257598
TI  - Binuclear copper(I) macrocycles synthesized via the weak-link approach.
AB  - The weak-link approach has been employed to synthesize a series of bimetallic
      Cu(I) macrocycles in high yield. Addition of phosphinoalkylether or -thioether
      ligands to [Cu(MeCN)4]PF6 produces "condensed" intermediates, [mu-(1,4
      (PPh2CH2CH2X)2Y)2Cu2][PF6]2 (X = S, O; Y = C6H4, C6F4), containing strong P-Cu
      bonds and weaker O-Cu or S-Cu bonds. The weak bonds of these intermediates can be
      cleaved through ligand substitution reactions to generate macrocyclic structures,
      [mu-(1,4-(PPh2CH2CH2X)2Y)2(Z)nCu2][PF6]2 (X = S, O; Y = C6H4, C6F4; Z = pyridine,
      acetonitrile, diimines, isocyanide) in nearly quantitative yields. The
      incorporation of tetrahedral Cu(I) metal centers into these macrocycles provides
      a pathway to complexes that differ from analogous d8 square planar macrocycles
      generated via this approach in their increased air stability, small molecule
      reactivity, and ability to form multiple structural isomers. Solid-state
      structures, as determined by single-crystal X-ray diffraction studies, are
      presented for condensed intermediates and an open macrocycle

PMID- 15257599
TI  - Sensing of sulfur dioxide by base metal thiolates: structures and properties of
      molecular NiN2S2/SO2 adducts.
AB  - The cis-dithiolate N2S2Ni complex bismercaptoethanediazacycloheptanenickel(II),
      (bme-dach)Ni or Ni-1', takes up two equivalents of sulfur dioxide in which
      thiolate-sulfur to SO2-sulfur interactions are well-defined by X-ray
      crystallography. Ni-1' x 2SO2, C9H18N2NiO4S4, yields monoclinic crystals
      belonging to the P2(1)/c space group: a = 10.308(4) angstroms, b = 13.334(5)
      angstroms, c = 10.842(4) angstroms, alpha = 90 degrees, beta = 91.963(6) degrees,
      gamma = 90 degrees, and Z = 4. Further characterization by nu(SO) IR
      spectroscopy, thermal gravimetric analysis, electronic spectroscopy, and visual
      color changes upon reversible SO2 adduct formation establish Ni-1' and the
      analogous bismercaptoethanediazacyclooctane derivative, (bme-daco)Ni, Ni-1, to be
      viable candidates for technical development as chemical sensors of this noxious
      gas. Visual SO2 detection limits of Ni-1 and Ni-1' are established at 25 and 100
      ppm, respectively. Both the Ni-1' x 2SO2 adduct and the Ni-1' reactant are air
      stable. In addition, the stability of Ni-1' x SO2 to vacuum and removal of SO2 by
      heating make Ni-1' a possible storage/controlled release complex for SO2 gas.

PMID- 15257600
TI  - XAFS and LIBD investigation of the formation and structure of colloidal Pu(IV)
      hydrolysis products.
AB  - Pu(IV) oxyhydroxide colloid growth is investigated with XAFS and LIBD. From
      combined results a model of colloid formation is proposed, which leads to a face
      centered cubic Pu sublattice having cation defects, as observed with EXAFS, and a
      linear dependency of log [Pu(IV)] on -log [H+] with slope -2, in accord with
      LIBD. The solubility for Pu(IV) measured with LIBD is close to the lower limit of
      the solubility curve from previously reported data.

PMID- 15257601
TI  - Crescent-shaped rhodium(I) complexes with bis(o-carboxymethylphenyl)triazenide.
AB  - Reaction of [[Rh(mu-Cl)(CO)2]2] with the triazene ArNNNHAr (Ar = o-CO2MeC6H4)
      produced the mononuclear complex [RhCl(ArNNNHAr)(CO)2] (1). Complex 1 reacted
      with KOH in methanol to give the dinuclear compound [[Rh(mu-ArNNNAr)(CO)2]2] (2),
      which showed a "mu-(1kappaN1,2kappaN3)-ArNNNAr" coordination mode for both
      bridging ligands. The dinuclear complex [[Rh(mu-ArNNNAr)(CO)2]2] (2) easily
      undergoes redistribution reactions in which the eight-membered "Rh2(NNN)2" core
      is broken. Thus, reaction of 2 with the anionic complex (NHEt3)[RhCl2(CO)2] gave
      the single-bridged complex (NHEt3)[Rh2(mu-ArNNNAr)Cl2(CO)4] (4), while the
      trinuclear complexes [Rh3(mu-ArNNNAr)(mu-Cl)(mu-CO)Cl(CO)4] (5) and [Rh3(mu
      ArNNNAr)2(mu-Cl)(mu-CO)(CO)3] (6) were isolated by addition of the neutral
      compound [[Rh(mu-Cl)(CO)2]2] to 2, depending on the molar ratio employed. The
      formation of 5 and 6 involved the loss of carbonyl groups and the coordination of
      the oxygen atoms of the CO2Me groups. The structures of 4, 5, and 6 have been
      determined by X-ray diffraction methods, which show the ability of bis(o
      carboxymethylphenyl)triazenide to act as bi-, tri-, and tetra-dentate ligand
      spanning dinuclear moieties in trinuclear complexes.

PMID- 15257602
TI  - Syntheses and structures of Ag(I)-containing coordination polymers and Co(II)
      containing supramolecular complex based on novel fulvene ligands.
AB  - Three new rigid conjugated fulvene ligands L1-L3 were synthesized. L1 and L3 have
      been prepared by an aroylation reaction of cyclohexyl-substituted
      cyclopentadienyl anions. L2 was prepared by the reaction of L1 with PhNHNH2 in
      hot enthanol. Six new coordination polymers, namely [Ag(C25H20N2O2)(ClO4)] x
      3.5C6H6 (1), [Ag2(mu-C31H24N4)(eta2-C6H6)(H2O)](ClO4)2 x (C6H6) x (H2O)0.5 (3),
      [Ag(C31H24N4)]SbF6 x solvate (4), [Ag(C31H24N4)](SbF6)2 x 2C6H6 x CH2Cl2 (5),
      [Ag(C25H20N2O2)2]SbF6 (6), and [Ag(C25H20N2O2)2]SbF6 (7), and one seven-membered
      cobaltacycle-containing complex, namely Co(C25H20N2O2)2(C2H5OH)2 (2), were
      obtained through self-assembly based on these three new fulvene lignads. L2-L3
      and compounds 1-7 have been fully characterized by infrared spectroscopy,
      elemental analysis, and single-crystal X-ray diffraction. The results indicate
      that the coordination chemistry of new fulvene ligands is versatile. They can
      bind metal ions not only through the terminal N-donors and fulvene carbon atoms
      into organometallic coordination polymers but also through the two chelating
      carbonyl groups into unusual seven-membered metallo-ring supramolecular
      complexes. In the solid state, ligands L1-L3 are luminescent. A blue-shift in the
      emission was observed between the free ligand L1 and the one incorporated into
      Co(II)-containing complex 2, and a red-shift in the emission was observed between
      the free ligand L3 and the one incorporated into Ag(I)-containing polymeric
      compounds 6 and 7.

PMID- 15257603
TI  - The first slipped pseudo-quadruple-decker complex of phthalocyanines.
AB  - The first slipped pseudo-quadruple-decker complex of phthalocyanines was formed
      unexpectedly upon treatment of the protonated double-decker SmIIIH(Pc)[Pc(alpha
      OC4H9)8] with NaOH. The supramolecular structure contains two double-decker units
      linked by two sodium ions by an extremely rare coordination mode of
      phthalocyanines in which an aza nitrogen atom and two oxygen atoms from
      neighboring alkoxy substituents form a tridentate ligand.

PMID- 15257604
TI  - Synthesis, structures, and physical properties of copper(II)-gadolinium(III)
      complexes combining ferromagnetic coupling and quadratic nonlinear optical
      properties.
AB  - Two copper(II)-gadolinium(III) metal complexes of formula CuIIGdIIILX3 are
      reported. H2L stands for the Schiff base ligand obtained by condensation of 3,4
      dimethoxysalicylaldehyde with ethylenediamine (complex 1) or 1R,2R-(+)-1,2
      diphenylethylenediamine (complex 2). While 1 reveals a centrosymmetric crystal
      structure, 2 crystallizes in the noncentrosymmetric P212121 space group and
      exhibits an efficiency 0.3 time that of urea in second harmonic generation. Due
      to a trend for dissociation in solution, the molecular hyperpolarizabilities
      (beta) cannot be determined experimentally for 1 and 2. Nevertheless, the
      electric field induced second harmonic (EFISH) technique, in connection with
      spectroscopic data and a ZINDO semiempirical approach, leads to a beta value of 
      6.5 x 10(-30) cm5 esu(-1), for the related CuIIL monomers, as an indicative range
      of magnitude in all these Schiff base complexes. In addition, 1 and 2 exhibit a
      ferromagnetic coupling in solid state with J = 3.3 and 1.3 cm-1, respectively (J
      being the parameter of the exchange Hamiltonian = -JSCu x SGd).

PMID- 15257605
TI  - Phase stability in the systems AeAl(2-x)Mgx (Ae = Ca, Sr, Ba): electron
      concentration and size controlled variations on the laves phase structural theme.
AB  - The systems AeAl(2-x)Mgx (Ae = Ca, Sr, Ba) display electron concentration induced
      Laves phase structural changes. However, the complete sequence MgCu2 --> MgNi2 -
      > MgZn2 with increasing x (decreasing electron count) is only observed for Ae =
      Ca. Compounds SrAl(2-x)Mgx (0 < x < or = 2) and BaAl(2-x)Mgx (x = 0.85 and 2.0)
      were synthesized and structurally characterized by X-ray diffraction experiments.
      For the Sr system the structural sequence CeCu2 --> MgNi2 --> MgZn2 occurs with
      increasing Mg content x. Thus, larger Sr does not allow the realization of the
      MgCu2 structure at low x. For Ae = Ba a binary compound BaAl2 does not exist, but
      more Ba-rich Ba7Al13 forms. The reinvestigation of the crystal structure of
      Ba7Al13 by selected area and convergent beam electron diffraction in a
      transmission electron microscope revealed a superstructure, which subsequently
      could be refined from single X-ray diffraction data. The formula unit of the
      superstructure is Ba21Al40 (space group P31m, Z = 1, a = 10.568(1) angstroms, c =
      17.205(6) angstroms). In Ba21Al40 a size match problem between Ba and Al present
      in Ba7Al13 is resolved. The structure of Ba7Al13 (Ba21Al40) can be considered as
      a Ba excess variant of the hexagonal MgNi2 Laves phase type structure. An
      incommensurately modulated variant of the MgNi2 structure is obtained for phases
      BaAl(2-x)Mgx with x = 0.8-1. At even higher Mg concentrations a structural change
      to the proper MgZn2 type structure takes place.

PMID- 15257606
TI  - Oxidative DNA strand scission induced by a trinuclear copper(II) complex.
AB  - A novel trinuclear copper(II) complex, Cu3-L (L = N,N,N',N',N' ',N' '-hexakis(2
      pyridyl)-1,3,5-tris(aminomethyl)benzene), exhibited efficient oxidative strand
      scission of plasmid DNA. The solution behavior of the complex has been studied by
      potentiometric titration, UV spectroscopy, and cyclic voltammetry. The data
      showed that there are three redox-active copper ions in the complex with three
      types of bound water. The complex demonstrated a moderate binding ability for
      DNA. Cu3-L readily cleaves plasmid DNA in the presence of ascorbate to give
      nicked (form II) and then linear (form III) products, while the cleavage
      efficiency using H2O2 is less than by ascorbate, suggesting that the cleavage
      mode of the trinuclear complex is somewhat different from the traditional Fenton
      like catalysis. Meanwhile, Cu3-L is far more efficient than its mononuclear
      analogue Cu-DPA (DPA = 2,2'-dipyridylamine) at the same [Cu2+] concentration,
      which suggests a possible synergy between the three or at least two Cu(II)
      centers in Cu3-L that contributes to its relatively high nucleolytic efficiency.
      Furthermore, the presence of standard radical scavengers does not have clear
      effect on the cleavage efficiency, suggesting the reactive intermediates leading
      to DNA cleavage are not freely diffusible radicals.

PMID- 15257607
TI  - Novel one-dimensional polymers generated from p-Ferrocenylbenzoate: syntheses,
      structures, and magnetic properties.
AB  - Treatment of p-ferrocenylbenzoate [p-HOOCH4C6Fc, Fc = (eta5-C5H5)Fe(eta5-C5H5)]
      with Mn(OAc)2 x 2H2O or Cd(OAc)2 x 2H2O afforded one-dimensional linear chain
      polymer [[Mn(OOCH4C6Fc)2(mu2-OH2)(H2O)2](H2O)]n (1), double-bridge polymer
      [Mn(mu2-OOCH4C6Fc)2(phen)]n (phen = phenanthroline) (2), and ladderlike framework
      [[Cd(mu2-OOCH4C6Fc)(eta2-OOCH4C6Fc)(bbp)](CH3OH)]n (bbp = 4,4'-trimethylene
      dipyridine) (3). The solution-state cyclic voltammograms indicate that the half
      wave potentials of the ferrocenyl moieties in these polymers are all shifted to
      positive potential compared to that of sodium p-ferrocenylbenzoate. Both 1 and 2
      behave as 1D Heisenberg Mn(II) chains with weak intrachain antiferromagnetic
      interactions between the local high-spin Mn(II) ions, and the exchange coupling
      parameters J (-5.20 and -3.25 cm(-1) for 1 and 2, respectively) are larger than
      those of most of the reported di-Mn(II) complexes that contain mu2-aqua and mu2
      carboxylato units and one-dimensional Mn(II) carboxylic polymers.

PMID- 15257608
TI  - Biologically relevant chemical reactions of N7-alkylguanine residues in DNA.

PMID- 15257609
TI  - Photosensitization of thymine nucleobase by benzophenone derivatives as models
      for photoinduced DNA damage: Paterno-Buchi vs energy and electron transfer
      processes.
AB  - Time-resolved and product studies have shown that there is a strong interaction
      between drugs containing the benzophenone chromophore and the free thymidine
      nucleoside. In quantitative terms, such an interaction is stronger for the lowest
      lying npi* triplet states (S-ketoprofen) than for mixed npi*-pipi* triplets
      (fenofibrate and fenofibric acid), as indicated by the quenching rate constants.
      This is consistent with a Paterno-Buchi photoreaction, where the initial step is
      the formation of a new bond between the excited carbonyl oxygen and one of the
      thymine olefinic carbons. Actually, oxetanes are obtained as photoproducts when
      benzophenone is irradiated in the presence of thymidine. Hence, triplet-triplet
      energy transfer resulting in formation of cyclobutane pyrimidine dimers, which
      would be thermodynamically disfavored, does not seem to play a major role.
      However, in DNA, the contribution of energy transfer could be higher, due to the
      lower energy of the thymine triplet in the biomacromolecule. These results are
      discussed in connection with the observed DNA damage upon photosensitization with
      ketoprofen, fenofibrate, and fenofibric acid.

PMID- 15257610
TI  - Interaction of Cd2+ with Zn finger 3 of transcription factor IIIA: structures and
      binding to cognate DNA.
AB  - Finger 3 of transcription factor IIIA of Xenopus laevis was synthesized and
      constituted with Zn(2+) or Cd(2+). The C-block element of the internal control
      region of the promoter of the 5S rRNA gene binds to the Zn-F3 and Cd-F3 with
      dissociation constants of 2.6 x 10(-5) and 1.5 x 10(-4) M, respectively.
      According to NMR spectroscopy, Zn-F3, as well as Cd-F3, exists as a
      conformational equilibrium that is not susceptible to structural analysis by NMR
      methods. To restrict the observed conformational flexibility, a mutant F3 (mF3),
      which differs from F3 in the number and type of amino acids between the cysteine
      and the histidine ligands, was synthesized. The affinity of Zn-mF3 for the C
      block DNA was greatly reduced relative to Zn-F3. Nevertheless, the metal ion
      dissociation constants of the Zn- and Cd-mF3 complexes remain similar to those of
      the native structures at 4.5 x 10(-9) and 3.2 x 10(-8) M, respectively. Zn-mF3 is
      more thermally stable than Cd-mF3, but both adopt similar conformations according
      to two-dimensional (1)H NMR spectroscopy. Each peptide displays a betabetaalpha
      fold for its backbone that is typical of this class of zinc finger domains.
      The(113)Cd ion in (113)Cd-mF3 is coupled to the protons of two cysteine and two
      histidine residues and characterized by a chemical shift of 567 ppm.

PMID- 15257611
TI  - Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals.
AB  - Arsenic is an environmental and occupational toxin. Dermatologic toxicities due
      to arsenic exposure are well-documented and include basal cell and squamous cell
      carcinomas. However, the mechanism of arsenic-induced skin cancer is not well
      understood. Recent studies indicate that arsenic exposure results in the
      generation of reactive oxygen species (ROS) and oxidative stress. Here, we
      examined the chemical nature of the specific ROS, studied the interrelationship
      among these species, and identified the specific species that is responsible for
      the subsequent DNA damage in a spontaneously immortalized keratinocyte cell line.
      We detected the formation of O(2)(*)(-) and H(2)O(2) in keratinocytes incubated
      with arsenite [As(III)] but not with arsenate. As(III)-induced DNA damage was
      detected in a concentration-dependent manner and evident at low micromolar
      concentrations. Catalase, an H(2)O(2) scavenger, eliminated H(2)O(2) and reduced
      the As(III)-mediated DNA damage. Superoxide dismutase, by enhancing the
      production of H(2)O(2) and (*)OH, significantly increased the As(III)-mediated
      DNA damage. Sodium formate, a competitive scavenger for (*)OH, and deferoxamine,
      a metal chelator, both reduced the DNA damage. These results suggest that
      exposure to arsenite generates O(2)(*)(-) and H(2)O(2), and (*)OH, derived from
      H(2)O(2), is responsible, at least in part, for the observed DNA damage. These
      findings demonstrate arsenic-induced formation of specific ROS and provide the
      direct evidence of (*)OH-mediated DNA damage in keratinocytes, which may play an
      important role in the mechanism for arsenic-induced skin carcinogenicity.

PMID- 15257612
TI  - Oxidation of raloxifene to quinoids: potential toxic pathways via a diquinone
      methide and o-quinones.
AB  - Raloxifene was approved in 1997 by the FDA for the treatment of osteoporosis in
      postmenopausal women, and it is currently in clinical trials for the
      chemoprevention of breast cancer. Before widespread use as a chemopreventive
      agent in healthy women, the potential cytotoxic mechanisms of raloxifene should
      be investigated. In the current study, raloxifene was incubated with GSH and
      either rat or human liver microsomes, and the metabolites and GSH conjugates were
      characterized using liquid chromatography-tandem mass spectrometry. Raloxifene
      was converted to raloxifene diquinone methide GSH conjugates, raloxifene o
      quinone GSH conjugates, and raloxifene catechols. For comparison, three
      raloxifene catechols were synthesized and characterized. In particular, 7
      hydroxyraloxifene was found to oxidize to the 6,7-o-quinone. As compared with
      raloxifene diquinone methide, which has a half-life of less than 1 s in phosphate
      buffer, the half-life of raloxifene 6,7-o-quinone was much longer at t(1/2) = 69
      +/- 2.5 min. The stability offered by raloxifene 6,7-o-quinone implies that it
      may be more toxic than raloxifene diquinone methide. Cytotoxicity studies in the
      human breast cancer cell lines S30 and MDA-MB-231 showed that 7-hydroxyraloxifene
      was more toxic than raloxifene in both cell lines. These results suggest that
      raloxifene could be metabolized to electrophilic and redox active quinoids, which
      have the potential to cause toxicity in vivo.

PMID- 15257613
TI  - Studies on toxic oil syndrome: stereoselective hydrolysis of 3
      (phenylamino)propane-1,2-diol esters by human pancreatic lipase.
AB  - The ingestion of rapeseed oil batches denatured with aniline and illegally
      refined and distributed by street vendors was responsible for toxic oil syndrome
      (TOS), an intoxication episode that took place in Spain in 1981, causing over 400
      deaths and affecting more than 20,000 people. Despite the intense research
      efforts carried out to date, the compounds responsible for that intoxication have
      not been elucidated. Nevertheless, epidemiological studies have pointed to fatty
      acid mono- and diesters of 3-phenylamino-1,2-propanediol (PAP) as the biomarkers
      of those toxic oil batches. The structure of these esters bears common features
      with that of triglycerides, which suggested that PAP esters could follow the
      route of lipids metabolism up to a certain extent. The incubation of racemic PAP
      dioleyl ester with human pancreatic lipase (hPL) led to the formation of the
      corresponding stereoisomeric monoesters bearing the oleyl residue at C-2,
      although a kinetic resolution in favor of the (S)-enantiomer was observed. These
      monoesters are unstable and in equilibrium with their corresponding regioisomers
      with the acyl residue at C-1, apparently without the intervention of the lipase.
      Finally, incubations of these latter monoesters with hPL led to the formation of
      the respective PAP enantiomers. Again, the kinetic resolution of this hydrolytic
      process favored the formation of the enantiomer with the (S)-configuration. Taken
      together, these results showed that PAP esters are substrates of hPL and that the
      two hydrolytic steps exhibit kinetic resolution in favor of the (S)-enantiomers.

PMID- 15257614
TI  - Urinary excretion of 3,N4-etheno-2'-deoxycytidine in humans as a biomarker of
      oxidative stress: association with cigarette smoking.
AB  - Smokers are known to have elevated levels of lipid peroxidation, a form of
      oxidative stress. Etheno DNA adduct formation can originate from endogenous lipid
      peroxidation or from exogenous exposure of carcinogens. Using a modified stable
      isotope dilution GC/negative ion chemical ionization/MS assay originally
      developed for urinary 3,N(4)-ethenocytosine (epsilonCyt), the nucleoside 3,N(4)
      etheno-2'-deoxycytidine (epsilondCyd) was detected for the first time in human
      urine. The presence of epsilondCyd in human urine was confirmed by
      LC/electrospray ionization/tandem MS. Concentrations of epsilondCyd in the 24 h
      urine samples from healthy individuals not occupationally exposed to industrial
      chemicals were in the range between 0 and 0.80 nM. A statistically significant
      correlation was established between cigarette smoking and urinary excretion of
      epsilondCyd after being adjusted for creatinine (p = 0.004). Furthermore, the
      urinary total antioxidant capacity was found to correlate inversely with the
      epsilondCyd levels (r = -0.50, p = 0.02). The results indicate that urinary
      epsilondCyd may provide a valuable noninvasive biomarker for oxidative DNA
      damage.

PMID- 15257615
TI  - In vitro biotransformation of 3,4-dihydro-6-hydroxy-2,2-dimethyl-7-methoxy-1(2H)
      benzopyran (CR-6), a potent lipid peroxidation inhibitor and nitric oxide
      scavenger, in rat liver microsomes.
AB  - The in vitro metabolism of 3,4-dihydro-6-hydroxy-2,2-dimethyl-7-methoxy-1(2H)
      benzopyran (CR-6), a potent lipid peroxidation inhibitor and scavenger of nitric
      oxide and peroxynitrite species that is currently in phase II trials for
      antitumoral therapy, has been investigated in rat liver microsomes in the
      presence of NADP(H). Five major metabolites were identified by comparison with
      authentic standards, namely, the quinone 2-(3'-hydroxy-3'-methylbutyl-5-methoxy
      1,4-benzoquinone (2a) and its ring-closed spiro form oxaspiro[4.5]-2,2-dimethyl-8
      methoxy-dec-8-ene-7,10-dione (2b), the hydroquinone 2-(3'-hydroxy-3'-methylbutyl)
      5-methoxyhydroquinone (3), the hydroxylated metabolite 3,4-dihydro-4,6-dihydroxy
      2,2-dimethyl-7-methoxy-1(2H)-benzopyran (4), and the catechol 3,4-dihydro-6,7
      dihydroxy-2,2-dimethyl-1(2H)-benzopyran (5). When the incubations were carried
      out in the presence of GSH, the HPLC peaks corresponding to the quinone
      metabolites 2a/b were absent and two novel products were formed showing MS
      fragmentation patterns consistent with the structure of GSH conjugates of quinone
      2a. The time dependence on the formation of metabolites 2a,b and 3 was measured
      in incubations induced with phenobarbital (PB), dexamethasone, and beta
      naphthoflavone (betaNF). For the dexamethasone-induced microsomes, the amount of
      hydroquinone 3 decreased from minute 10 to minute 30 while that of 2a,b increased
      in a complementary manner. Similar effects were observed for the incubations
      carried out using PB- and betaNF-induced microsomes. On the other hand, CR-6
      inhibited 7-ethoxyresorufin O-dealkylation activity (IC(50) = 25 microM) in
      incubations with betaNF-induced microsomes. Likewise, addition of
      pentoxyresorufin to the incubations of CR-6 with PB-induced microsomes showed a
      time-dependent inhibition (IC(50)= 75 microM) of the dealkylation activity. These
      results are in agreement with the putative generation of reactive metabolites
      from CR-6 that could deactivate P450 1A and P450 2B, respectively. When these
      incubations were carried out in the presence of 10 mM GSH, the inhibition of P450
      2B could be partially prevented. Finally, preincubation of CR-6 with liver
      microsomes from PB-induced rats resulted in a strong increase in microsomal
      glutathione S-transferase (mGST) activity (up to a maximum of approximately 5
      fold). When the preincubation was carried out in the presence of 10 mM GSH, the
      activation of mGST was blocked. Overall, these results suggest that CR-6
      undergoes in vitro biotransformation indicative of the involvement of thiol
      reactive metabolites.

PMID- 15257616
TI  - Dimethylthioarsenicals as arsenic metabolites and their chemical preparations.
AB  - Two unidentified arsenic metabolites were detected in the liver of rats on a gel
      filtration column by HPLC inductively coupled argon plasma mass spectrometry
      after an injection of dimethylarsinic (DMA(V)), dimethylarsinous (DMA(III)),
      monomethylarsonic (MMA(V)), or monomethylarsonous (MMA(III)) acid. The same
      arsenicals were also produced in vitro by incubation of DMA(III) in the liver
      supernatant but not by DMA(V). The two arsenic metabolites eluted at the same
      retention times as those of the two arsenicals prepared by reaction of DMA(V)
      with either thiosulfate plus disulfite or hydrogen sulfide or sodium sulfide plus
      sulfuric acid. The faster and slower eluting products on a gel filtration column
      were assigned as dimethyldithioarsinic acid (dimethylarsinodithioic acid)
      (DMTA(V)) and dimethylthioarsinous acid (DMTA(III)) from mass spectrometric data
      at m/z = 170 and 138 by electrospray ionization mass spectrometry with negative
      and positive ion modes, respectively. They were prepared selectively by reacting
      DMA(V) with hydrogen sulfide or sodium sulfide plus sulfuric acid under different
      reaction conditions. DMA(III) but not DMA(V) was transformed to DMTA(III) and
      DMTA(V) in the presence of sodium sulfide in vitro, suggesting that DMA(V) is
      reduced to DMA(III) with hydrogen sulfide, thiolated to DMTA(III), and then
      further thiolated oxidatively to DMTA(V). Metabolically, it is assumed that
      DMA(III) is transformed to DMTA(III) in the presence of sulfide ions, and then,
      DMTA(III) is oxidatively thiolated to DMTA(V). As the chemical species produced
      by reduction with the Reay and Asher method are DMTA(III) and DMTA(V), and
      different from DMA(III), the studies carried out with DMA(III) with the Reay and
      Asher method have to be reexamined.

PMID- 15257617
TI  - Effect of tea catechins on the change of glutathione levels caused by Pb(++) in
      PC12 cells.
AB  - Our previous research showed that tea catechins could significantly increase the
      viability of lead-exposed PC12 cells. Whereas the cellular thiol status is known
      to be responsible for protecting against lead-induced toxicity, whether the role
      of tea catechins on lead-induced PC12 cell toxicity is related to the metabolism
      of intracellular thiol compounds remained vague. In the present study, it was
      found that Pb(2+) significantly decreased reduced glutathione (GSH)/oxidative
      glutathione (GSSG) and protein sulfhydryl groups (PSH)/glutathione-protein mixed
      disulfide (GSSP) ratios as well as glutathione reductase activities in a
      concentration-dependent manner. Both (-)-epicatechin and (-)-epicatechin gallate
      (ECG) supplementation resulted in an increased GSH/GSSG ratio and glutathione
      reductase activities. The galloylated catechins (ECG or (-)-epigallocatechin
      gallate) treatment significantly decreased the GSSP levels and increased the
      intracellular PSH/GSSP ratio in lead-exposed PC12 cells. To our surprise, as
      compared with the group treated by lead acetate, 100 microM EGC treatment
      following lead exposure significantly decreased GSH/GSSG and PSH/GSSP ratios, as
      well as glutathione reductase activities. The results suggested that the effect
      of tea catechins on the intracellular thiols status in PC12 cells was different,
      which may be related to their chemical structures and/or regulation of special
      gene expression properties.

PMID- 15257618
TI  - Synthesis, characterization, and identification of N7-guanine adducts of isoprene
      monoepoxides in vitro.
AB  - Isoprene (IP, 2-methylbuta-1,3-diene) is ubiquitous in the environment through
      emission by plants, combustion processes, and endogenous formation and exhalation
      by mammals, including humans. IP is also an industrial chemical, widely used in
      the manufacture of synthetic rubber and plastics. Like butadiene, IP is
      metabolized to reactive epoxides, which form adducts with macromolecules, and is
      a demonstrated carcinogen in mice. To date, DNA adducts of IP monoepoxides have
      not been reported. We report here on the formation of N7-guanine (N7-Gua) adducts
      of isoprene-1,2-oxide (IP-1,2-O, 2-ethenyl-2-methyloxirane) and isoprene-3,4
      oxide (IP-3,4-O, propen-2-yloxirane). DNA adducts are useful as biomarkers to
      estimate exposure, as well as to investigate mechanisms of IP carcinogenesis.
      Incubation of 2'-deoxyguanosine with the monoepoxides followed by deglycosylation
      gave four N7-Gua adducts that were isolated by HPLC and characterized by high
      resolution FAB(+)-MS, ESI(+)-MS, ESI(+)-MS/MS, and (1)H NMR and two-dimensional
      heteronuclear (1)H, (13)C correlation NMR spectrometry. IP-1,2-O and IP-3,4-O
      reacted at both terminal and internal oxirane carbons to form the following
      regioisomeric adducts at Gua N7: N7-(2'-hydroxy-2'-methyl-3'-buten-1'-yl)guanine,
      N7-(1'-hydroxy-2'-methyl-3'-buten-2'-yl)guanine, N7-(1'-hydroxy-3'-methyl-3'
      buten-2'-yl)guanine, and N7-(2'-hydroxy-3'-methyl-3'-buten-1'-yl)guanine. The
      same adducts were identified by UV spectra, HPLC retention times, and LC/ESI(+)
      MS in the neutral thermal hydrolysates of single- and double-stranded calf thymus
      DNA after incubation with IP monoepoxides. Characterization of the N7-Gua adducts
      identified in incubations of DNA with IP monoepoxides represents the first step
      toward establishing biomarkers of IP metabolism and exposure.

PMID- 15257619
TI  - Autoxidative transformation of chiral omega6 hydroxy linoleic and arachidonic
      acids to chiral 4-hydroxy-2E-nonenal.
AB  - Recently, we established that 13S-hydroperoxy-linoleic acid is converted to 4S
      hydroperoxy-nonenal (4S-HPNE) during autoxidation, implicating hydrogen
      abstraction from C-8 as an initiating step [Schneider, C., et al. (2001) J. Biol.
      Chem. 275, 20831-20838]. On the basis of the proposed mechanism, an equivalent
      initiating reaction could occur from the corresponding 13S-hydroxy acid. Herein,
      we examined the outcome of autoxidation reactions of the omega6 hydroxy fatty
      acids, 13S-hydroxyoctadecadienoic acid and 15S-hydroxyeicosatetraenoic acid, as
      compared with reactions of the corresponding hydroperoxy substrates. Autoxidation
      of the hydroxy starting materials (37 degrees C, dry film) yielded 4-hydroxy
      nonenal (4-HNE) as a prominent polar metabolite (and not the 4-hydroperoxide),
      whereas the hydroperoxide starting materials gave rise to 4-HPNE. Stereochemical
      analysis showed that the optical purity of the 4-hydroxy group of 4-HNE precisely
      matched the optical purity of the 15S- or 13S-hydroxy group of the starting fatty
      acid substrate (98 and 90% S, respectively). The hydroperoxide 15S-HPETE (98%
      15S) gave rise to 4S-HPNE, also with retention of optical purity (98% 4S). The
      preservation of stereochemical configuration provides evidence that aldehyde
      formation does not involve participation of the hydro(pero)xy group and indicates
      a similar mechanism for the formation of 4-HNE and 4-HPNE during autoxidation of
      omega6 hydro(pero)xy fatty acids. Our results establish, moreover, that omega6
      hydroxy fatty acids are potential precursors of reactive cytotoxic aldehydes in
      biological systems.

PMID- 15257620
TI  - Chemical properties of the leinamycin-guanine adduct in DNA.
AB  - The reaction of the antitumor agent leinamycin with thiols converts this natural
      product into an episulfonium ion that alkylates the N7-position of guanine
      residues in double-stranded DNA. It is reported here that depurination of this
      adduct is unusually facile, occurring with a half-life of about 3.5 h at pH 7 and
      37 degrees C in duplex DNA. This is one of the most rapid depurination reactions
      ever observed for an N7-alkylguanine residue. The rate constant for the
      depurination reaction was measured at several temperatures, and the activation
      parameters were calculated from the data. The energy of activation (E(a)) for
      this reaction is 24.6 kcal/mol, and the Arrhenius A value is 1.2 x 10(13) s(-1).
      These values correspond to a DeltaH(++) = 24.0 kcal/mol and DeltaS(++) = -0.78 eu
      and are consistent with the expected unimolecular (D(N) + A(N)) mechanism for the
      depurination reaction. Changes in ionic strength (0-500 mM NaCl) or pH (3-8) do
      not significantly alter the rate of depurination, and the base excision repair
      protein Aag, which removes a variety of N7-alkylguanine residues from duplex DNA,
      does not excise the leinamycin-guanine adduct. Possible biological implications
      of this rapid depurination process are considered. Finally, during the course of
      these studies, the release of hydrolyzed leinamycin (4; Scheme 1) from leinamycin
      modified DNA was observed. This result suggests that leinamycin may be a
      reversible DNA alkylating agent.

PMID- 15257621
TI  - Adenine-containing DNA-DNA cross-links of antitumor nitrogen mustards.
AB  - Nitrogen mustards (NMs) are useful chemotherapeutic agents in the treatment of
      lymphoma, leukemia, multiple myeloma, and ovarian carcinoma. The antitumor
      activity of NMs has been attributed to their ability to cross-link the twin
      strands of DNA. The resulting bifunctional lesions, if not repaired, can inhibit
      DNA replication and transcription, eventually leading to cell cycle arrest,
      apoptosis, and the inhibition of tumor growth. The predominant bifunctional DNA
      lesions of NM have been reported to involve the distal guanine bases in the
      opposite strands of 5'-GNC sequences. In the present work, the formation of
      guanine-adenine and adenine-adenine adducts of N,N-bis(2-chloroethyl)methylamine
      (mechlorethamine) in double-stranded DNA is demonstrated. Guanine-adenine cross
      links of mechlorethamine were identified as N-(2-[N3-adenyl]ethyl)-N-(2-[N7
      guanyl]ethyl)methylamine (N3A-N7G-EMA), N-(2-[N1-adenyl]ethyl)-N-(2-[N7
      guanyl]ethyl)methylamine, and N-(2-[N(6)-adenyl]ethyl)-N-(2-[N7
      guanyl]ethyl)methylamine. All three adducts were produced interstrand, while N3A
      N7G-EMA was the dominant intrastrand G-A cross-link. The prevalent adenine
      adenine mechlorethamine lesions have the structure of N,N-bis(2-[N3
      adenyl]ethyl)methylamine (bis-N3A-EMA). DNA-derived lesions have the same HPLC
      retention times, UV spectra, and MS/MS fragmentation patterns as the authentic
      standards prepared independently. bis-N3A-EMA lesions were produced in a
      concentration-dependent manner in calf thymus DNA treated with increasing amounts
      of mechlorethamine. Furthermore, HPLC-ESI-MS/MS analysis was used to demonstrate
      the formation of analogous N3-N3 adenine lesions in DNA treated with aromatic
      nitrogen mustards, N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid and L
      phenylalanine mustard. The presence of cross-linked adenine-adenine lesions may
      explain the enhanced cytotoxicity and mutagenicity of NMs in cells deficient in
      N3-alkyladenine glycosylase.

PMID- 15257622
TI  - Quantification of urinary excretion of 1,N6-ethenoadenine, a potential biomarker
      of lipid peroxidation, in humans by stable isotope dilution liquid chromatography
      electrospray ionization-tandem mass spectrometry: comparison with gas
      chromatography-mass spectrometry.
AB  - Etheno DNA adducts are promutagenic DNA lesions derived from exogenous as well as
      endogenous sources. The levels of etheno adducts in tissue DNA are elevated in
      cancer prone tissues, and the urinary excretion of etheno adducts is associated
      with oxidative stress. In this report, a new assay based on isotope dilution
      liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI
      MS/MS) is developed for the quantification of 1,N(6)-ethenoadenine (epsilonAde)
      in human urine samples without the need for derivatization. Sample purification
      before analysis by MS only requires a reversed phase solid phase extraction
      column. Two multiple reaction monitoring transitions with two product ion
      fragments generated from a common parent ion were used to quantify urinary
      epsilonAde. The detection limit of epsilonAde using LC-ESI-MS/MS is 2 pg injected
      standard epsilonAde on-column, and the assay allows accurate quantification of
      urinary epsilonAde at concentrations higher than 10 pg/mL. The presence of
      epsilonAde in human urine is confirmed by the collision-induced daughter ion
      spectrum. Using this assay, the levels of epsilonAde in the 24 h urine samples
      from 18 healthy individuals are determined, and the results are in very good
      agreement with those obtained using isotope dilution gas chromatography-negative
      ion chemical ionization-mass spectrometry. The high specificity and simple sample
      pretreatment of this LC-ESI-MS/MS method render it a valuable tool in measuring
      epsilonAde in the complex mixture of human urine as a promising noninvasive
      biomarker for DNA damage associated with oxidative stress and for cancer
      chemoprevention studies.

PMID- 15257623
TI  - Activation of bis-electrophiles to mutagenic conjugates by human O6-alkylguanine
      DNA alkyltransferase.
AB  - O(6)-Alkylguanine DNA-alkyl transferase (AGT) has been shown to conjugate both
      1,2-dibromoethane and dibromomethane, yielding AGT inactivation, DNA-AGT cross
      linking, and enhanced mutagenicity. A variety of related chemicals were examined
      to determine if similar phenomena occur. Among the compounds examined in these
      systems (histidine operon reversion in Escherichia coli and Salmonella
      typhimurium tester strains), a strong halide order was generally observed, with
      increasing activities in the order I > Br >> Cl. At least one Br atom appeared to
      be required for human AGT-dependent mutations, and compounds with only Cl did not
      inhibit AGT and were not activated to genotoxins. Of a series of haloforms tested
      (CHX(3), X = Br or Cl), all were without effect. Among a series of alpha,omega
      disubstituted dihaloalkanes (Br or I), the inactivation of AGT increased with
      methylene chain length (at least up to n = 5) but the most mutagenic activity
      (AGT-dependent) was seen with n = 1-3. The effects with n = 1 or 2 were expected
      from previous results; the mutagenic effect with n = 3 and the reduction with n >
      3 may represent a balance between AGT reaction, stability, and reactivity, in the
      absence of anchimeric assistance. A strong AGT-dependent mutation was observed
      for 1,3-butadiene diepoxide. We conclude that numerous bis-electrophiles show AGT
      dependent activation to mutagenic conjugates. Haloforms and dichloroalkanes are
      therefore not an issue, but bromohaloalkanes and 1,3-butadiene diepoxide are
      potential problems. These observations are of relevance in considering toxicity
      and risks of some chemicals used in industrial applications.

PMID- 15257625
TI  - Newer treatment options for skin and soft tissue infections.
AB  - In recent years, serious skin and soft tissue infections (SSTIs) caused by
      multidrug resistant pathogens have become more common. While the majority of
      SSTIs are caused by Staphylococcus aureus or beta-haemolytic streptococci that
      are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and
      vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens
      has created a need for different therapeutic agents, such as linezolid,
      quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and
      fluoroquinolones. This review focuses on agents presently in clinical development
      for the treatment of SSTIs caused by Gram-positive pathogens such as
      staphylococci, streptococci and enterococci including methicillin-resistant S.
      aureus (MRSA) and vancomycin-resistant enterococci (VRE). Newer-generation
      carbapenems, such as meropenem and ertapenem, are characterised by a broad
      spectrum of activity against Gram-positive and -negative aerobes and anaerobes,
      and are resistant to hydrolysis by many beta-lactamases. Current-generation
      fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have
      demonstrated better eradication rates for S. aureus than conventional penicillin
      and cephalosporins. These antimicrobial agents can be used to treat methicillin
      susceptible staphylococcal and streptococcal strains. Oxazolidinones,
      streptogramin combinations and cyclic lipopeptides have novel mechanisms of
      action and have been studied in several multinational phase III clinical trials
      in the treatment of complicated and uncomplicated SSTIs. They possess a broad
      spectrum of activity against multidrug-resistant pathogens, including MRSA and
      VRE. Linezolid has been shown to be active against a wide variety of community
      acquired and nosocomial antimicrobial-resistant pathogens with comparability to
      vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic
      lipopeptides such as daptomycin have a unique mechanism of action by disruption
      of bacterial membrane electric potentials with less likelihood for development of
      cross-resistance. Daptomycin has recently been US FDA approved for the treatment
      of complicated SSTI. However, rapid development of resistance to some of these
      newer agents has already been reported and this trend magnifies the importance of
      further need for effective antimicrobial agents. Several investigational agents,
      such as dalbavancin, oritavancin and tigecycline, are in advanced stages of
      development and are likely to proceed to licensing in the next few years. With
      their long half-lives, these agents have an advantage of less frequent dose
      administration with more rapid bactericidal activity and less likelihood for
      development of resistance. However, because of their proven activity against
      highly resistant organisms, these antibacterial agents should be reserved only
      for life-threatening situations and/or when resistant pathogens are suspected.
      Rational antimicrobial use coupled with awareness of infection control measures
      is paramount to avert the emergence of multidrug-resistant organisms.

PMID- 15257626
TI  - Drug treatment of overactive bladder: efficacy, cost and quality-of-life
      considerations.
AB  - Overactive bladder (OAB) syndrome has been recognised by the International
      Continence Society as an important symptom syndrome that affects millions of
      people worldwide. Quality of life is affected in most people with OAB; however,
      the aetiology is unknown. Some researchers suggest that it is because of a damage
      to central inhibitory pathways or sensitisation of peripheral afferent terminals
      in the bladder, others suggest that it is a bladder muscle problem; the reality
      is probably a spectrum encompassing these two main explanations. Therefore,
      treatment is difficult and is aimed at alleviating symptoms (being those of
      urgency, with or without urge incontinence, usually with frequency and nocturia)
      rather than treating the cause. A thorough patient history and physical
      examination are required to establish a possible diagnosis. Frequency/volume
      charts form an important aid to the diagnosis. Once a presumptive diagnosis is
      made, conservative management forms the first line of treatment and includes
      lifestyle modifications, bladder training and pelvic floor exercises. If this
      fails, pharmacotherapy, in the form of anticholinergic drugs, is initiated. There
      are many antimuscarinic drugs, for example oxybutynin, tolterodine and trospium
      chloride. Each has a different specificity to bladder muscarinic receptors, thus
      producing different adverse effect profiles (e.g. dry mouth, blurred vision and
      constipation). Different individuals experience these adverse effects to
      different extents. New anticholinergic drugs, that have undergone phase III
      trials and are more specific to the muscarinic M3 human bladder receptor, are
      being introduced to the market in 2004 (e.g. solifenacin succinate and
      darifenacin). In addition to adverse effect profile, cost and improvement in
      quality of life are important factors in choosing treatment. Further research is
      being conducted on other types of drugs and different administration modalities,
      for example intravesical botulinum toxin A. Sacral nerve neuromodulation is
      emerging as a potential treatment, but if all treatments fail then surgery is the
      last resort.

PMID- 15257627
TI  - Drug treatment of intermittent claudication.
AB  - The US FDA has approved two drugs for the management of intermittent
      claudication: pentoxifylline and cilostazol. The mechanism of action that
      provides symptom relief with pentoxifylline is poorly understood but is thought
      to involve red blood cell deformability as well as a reduction in fibrinogen
      concentration, platelet adhesiveness and whole blood viscosity. The recommended
      dose of pentoxifylline is 400 mg three times daily with meals. Cilostazol is a
      potent, reversible, phosphodiesterase III inhibitor. The inhibition of
      phosphodiesterase allows for the increased availability of cyclic adenosine
      monophosphate (cAMP). cAMP mediates many agonist-induced platelet inhibitory,
      vasodilatory and vascular antiproliferative responses. Cilostazol, at a dose of
      100 mg twice daily, is recommended to be taken 30 minutes before or 2 hours after
      breakfast and dinner. In addition to pentoxifylline and cilostazol, clinical
      trials indicate many other drugs may relieve the symptoms of intermittent
      claudication. Ginkgo biloba, available as an over-the-counter extract, provides
      symptom relief comparable to pentoxifylline. Two European agents, naftidrofuryl
      and buflomedil, also have efficacy that is reported to be similar to
      pentoxifylline. Policosanol is a mixture of fatty alcohols derived from honeybee
      wax which, according to very limited data, reduces symptoms of claudication.
      Amino acids, certain peptides and prostaglandins may have a therapeutic role.
      Finally, novel approaches including angiogenesis mediated by growth factors, are
      currently under investigation.

PMID- 15257628
TI  - A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via
      Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive
      pulmonary disease.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) can be effectively
      treated by the use of bronchodilator therapies delivered by inhalation. Berodual
      is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and
      the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been
      available for the treatment of asthma and COPD in a pressurised metered dose
      inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used
      device for the delivery of inhaled medications, such as IB/FEN. However, most
      conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are
      currently being withdrawn because of their detrimental effects on the
      environment. This has resulted in alternative methods of drug delivery being
      developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free
      inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be
      easily inhaled. Scintigraphic studies have shown that this improves deposition of
      drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI.
      A clinical development programme has been conducted to compare the efficacy and
      safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in
      the treatment of patients with asthma or COPD. Five clinical studies (two phase
      II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800
      microg via Respimat SMI in single and multiple dose administration regimens. Four
      of the trials were conducted in patients with asthma (three in adults and one in
      children), while one phase III trial was conducted in patients with COPD. In
      phase III, 2058 patients participated, with a total of 1112 patients treated with
      IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI
      was given in one actuation compared with two actuations with the CFC-MDI. In the
      paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer
      device. The results of the trials demonstrated that IB/FEN via Respimat SMI
      allows a reduction in the nominal dose of IB/FEN, while offering similar
      therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates
      the need for a spacer.

PMID- 15257629
TI  - Telithromycin.
AB  - Telithromycin, the first member of the ketolide antibacterials, has good activity
      against community-acquired respiratory pathogens, including multiple-drug
      resistant strains of Streptococcus pneumoniae. Telithromycin 800 mg once daily
      has been US FDA approved for the treatment of acute bacterial sinusitis (ABS;
      treatment duration 5 days), acute bacterial exacerbations of chronic bronchitis
      (AECB; 5 days) and mild-to-moderate community-acquired pneumonia (CAP; 7-10
      days). In patients with CAP, telithromycin was as effective as amoxicillin 1000
      mg three times daily for 10 days, clarithromycin 500 mg twice daily for 10 days
      or trovafloxacin 200 mg once daily for 7-10 days. In patients with AECB,
      telithromycin was as effective as a 10-day regimen of amoxicillin/clavulanic acid
      500/125 mg three times daily, cefuroxime axetil 500 mg twice daily or
      clarithromycin 500 mg twice daily. In patients with ABS, telithromycin was as
      effective as a 10-day course of amoxicillin/clavulanic acid 500/125 mg three
      times daily or cefuroxime axetil 250 mg twice daily. Telithromycin was generally
      well tolerated and most adverse events were of mild-to-moderate severity and
      transitory. The most common adverse events with telithromycin were diarrhoea and
      nausea (10.8% and 7.9% of 2702 patients in clinical trials); these events
      occurred in 8.6% and 4.6% of 2139 comparator-treated patients.

PMID- 15257633
TI  - Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder.
AB  - Aripiprazole, a quinolinone derivative, is an atypical antipsychotic drug
      indicated for the treatment of adult patients with schizophrenia. Aripiprazole 10
      or 15 mg once daily is effective and well tolerated in patients with
      schizophrenia or schizoaffective disorder. Although aripiprazole has only been
      directly compared with haloperidol and olanzapine in treatment-responsive
      patients to date, current data generally indicate that aripiprazole has a
      beneficial profile in terms of a low potential for bodyweight gain. Dosage
      titration is not necessary and the drug is effective in the first few weeks of
      treatment. Head-to-head comparative trials with atypical antipsychotic agents are
      required, as are long-term (> or =1 year) studies, to fully define the position
      of aripiprazole in relation to other antipsychotic drugs. Aripiprazole is a
      valuable new therapeutic option in the management of patients with schizophrenia.
      PHARMACOLOGICAL PROPERTIES: Aripiprazole is a quinolinone derivative with a high
      affinity for dopamine D2 and D3 receptors, and serotonin 5-HT1A, 5-HT2A and 5
      HT2B receptors. The mechanism of action of aripiprazole is not yet known, but
      evidence suggests that its efficacy in the treatment of the positive and negative
      symptoms of schizophrenia and its lower propensity for extrapyramidal symptoms
      (EPS) may be attributable to aripiprazole's partial agonist activity at dopamine
      D2 receptors. At serotonin 5-HT1A receptors, in vitro studies have shown that
      aripiprazole acts as a partial agonist whereas at serotonin 5-HT2A receptors
      aripiprazole is an antagonist. The main active metabolite, dehydro-aripiprazole,
      has affinity for dopamine D2 receptors and thus has some pharmacological activity
      similar to that of the parent compound. Aripiprazole is rapidly absorbed after
      oral administration. The mean time to peak plasma concentration is 3 hours
      following multiple-dose administration of aripiprazole 10 or 15 mg and the
      absolute oral bioavailability of the drug is 87%. Steady-state plasma drug
      concentrations are achieved by 14 days; however, the drug appears to accumulate
      over this period, since mean peak plasma concentration and mean area under the
      plasma concentration-time curve values of aripiprazole 10 or 15 mg/day are 4-fold
      greater on day 14 than on day 1. This accumulation may be expected, since the
      mean elimination half-life of a single dose of aripiprazole is about 75 hours.
      Aripiprazole has extensive extravascular distribution and more than 99% of
      aripiprazole and dehydro-aripiprazole (the main active metabolite of
      aripiprazole) is bound to plasma protein. Elimination of the drug is primarily
      hepatic; the cytochrome P450 (CYP) 3A4 and CYP2D6 enzyme systems transform
      aripiprazole to dehydro-aripiprazole, with the latter enzyme system subject to
      genetic polymorphism. Thus, dosage adjustment of aripiprazole is necessary when
      it is coadministered with CYP3A4 and CYP2D6 inhibitors (since aripiprazole
      concentration is increased) and with inducers of CYP3A4 (since aripiprazole
      concentration is decreased). THERAPEUTIC EFFICACY: The efficacy of aripiprazole
      has been demonstrated in patients with schizophrenia or schizoaffective disorder.
      In general, significant reductions from baseline in mean Positive and Negative
      Syndrome Scale total, positive and negative symptom scores, and Clinical Global
      Impression Severity of Illness scores were observed in patients with acute
      relapse of chronic schizophrenia or schizoaffective disorder receiving
      recommended (10 or 15 mg/day) or higher-than-recommended (20 or 30 mg/day)
      dosages of aripiprazole versus those receiving placebo in three well controlled,
      short-term trials. No additional therapeutic benefit was observed at the higher
      than-recommended dosages. The drug is effective as early as the first or second
      week of treatment. The efficacy of aripiprazole was maintained for up to 52
      weeks. The drug was significantly more effective than placebo in preventing
      relapse in patients with stable chronic schizophrenia in a 26-week, randomised
      trial. In a 52-week trial in patients with acute relapse of schizophrenia, the
      percentage of responders maintaining a response at study end was 77% of
      aripiprazole versus 73% of haloperidol recipients. Aripiprazole may improve
      cognitive function. In a nonblind, 26-week trial, patients with chronic
      schizophrenia receiving aripiprazole 30 mg/day experienced similar (general
      cognitive function) or better (verbal learning) changes from baseline in the
      neurocognitive parameters evaluated compared with recipients of olanzapine 10-15
      mg/day. TOLERABILITY: Aripiprazole 10-30 mg/day was generally well tolerated. The
      tolerability profile of aripiprazole was broadly similar to that observed with
      placebo in a meta-analysis of short-term trials in patients with acute relapse of
      schizophrenia or schizoaffective disorder and in a 26-week trial in patients with
      chronic stable schizophrenia. The most frequent treatment-emergent adverse events
      included insomnia and anxiety, and additionally, headache and agitation (in short
      term trials) or akathisia and psychosis (in a 52-week trial). In general, the
      drug was associated with a placebo-level incidence of EPS and EPS-related adverse
      events. Significantly fewer aripiprazole recipients experienced EPS-related
      adverse events than haloperidol recipients in a 52-week trial. Changes in
      severity of EPS were minimal and usually no different from those observed with
      placebo. Moreover, there was less severe EPS in the aripiprazole group than the
      haloperidol group in a long-term trial. Treatment-emergent tardive dyskinesia was
      reported in only 0.2% of patients receiving aripiprazole (short-term trials), an
      incidence similar to that seen in placebo recipients (0.2%). Aripiprazole has a
      low propensity to cause clinically significant bodyweight gain,
      hyperprolactinaemia or corrected QT interval prolongation in patients with
      schizophrenia or schizoaffective disorder. In addition, there were no clinically
      relevant differences in mean changes from baseline in measures of diabetes and
      dyslipidaemia between the aripiprazole or placebo groups in a 26-week, placebo
      controlled trial.

PMID- 15257632
TI  - Oral sodium phosphate solution: a review of its use as a colorectal cleanser.
AB  - Oral sodium phosphate solution (Fleet Phospho-soda, Casen-Fleet Fosfosoda is a
      low-volume, hyperosmotic agent used as part of a colorectal-cleansing preparation
      for surgery, x-ray or endoscopic examination. The efficacy and tolerability of
      oral sodium phosphate solution was generally similar to, or significantly better
      than, that of polyethylene glycol (PEG) or other colorectal cleansing regimens in
      patients preparing for colonoscopy, colorectal surgery or other colorectal
      related procedures. Generally, oral sodium phosphate solution was significantly
      more acceptable to patients than PEG or other regimens. The use of this solution
      should be considered in most patients (with the exception of those with
      contraindications) requiring colorectal cleansing. PHARMACOLOGICAL PROPERTIES:
      After the first and second 45 mL dose of oral sodium phosphate solution, the mean
      time to onset of bowel activity was 1.7 and 0.7 hours and the mean duration of
      activity was 4.6 and 2.9 hours. Bowel activity ceased within 4 hours of
      administration of the second dose in 83% of patients. Elevations in serum
      phosphorus and falls in serum total and ionised calcium from baseline occurred
      during the 24 hours after administration of oral sodium phosphate solution in
      seven healthy volunteers. These changes were not associated with significant
      changes in clinical assessments. The decrease in serum potassium levels after
      administration of oral sodium phosphate solution was negatively correlated with
      baseline intracellular potassium levels. THERAPEUTIC USE: A regimen that
      administered the first dose of sodium phosphate on the previous evening and a
      second dose on the morning of the procedure (10-12 hours apart) was significantly
      more effective than PEG-based regimens for colorectal cleansing in preparation
      for colonoscopy, sigmoidoscopy or colorectal surgery. A regimen that administered
      both doses of oral sodium phosphate on the day prior to the procedure offered no
      colorectal cleansing advantage over PEG-based regimens and was significantly less
      effective than an oral sodium phosphate solution regimen that administered one
      dose on the previous evening and a second dose on the morning of the procedure.
      Oral sodium phosphate solution was generally as effective as other colorectal
      cleansing solutions (including magnesium citrate-containing regimens with sodium
      picosulfate). The direct costs of a diagnostic colonic examination with oral
      sodium phosphate solution were less than those with PEG (US465 dollars vs US503
      dollars per patient; 1995 values), according to data from a US study. Oral sodium
      phosphate solution was significantly more effective than a commercially available
      tablet formulation as a colorectal cleanser prior to colonoscopy (data from one
      study only). TOLERABILITY: Oral sodium phosphate solution administered as two 45
      mL doses (generally 10-12 hours apart) was well tolerated in well designed trials
      in which adults with major comorbid conditions were excluded. Sodium phosphate
      associated adverse events were mostly gastrointestinal (including abdominal
      pain/cramping, abdominal fullness and/or bloating, anal or perianal irritation or
      soreness, nausea, vomiting or hunger pains), although dizziness,
      weakness/fatigue, thirst, chest pain, chills, headache and sleep loss were also
      reported. Faecal incontinence was commonly reported in the elderly. Three doses
      (administered 10 minutes apart) of 15 mL of oral sodium phosphate solution, each
      diluted in 250 mL of clear fluid was associated with less vomiting than one 45 mL
      dose of the solution diluted in 250 mL of clear fluid (data from one study). In
      patients without major comorbid conditions, oral sodium phosphate has been
      associated with transient and clinically inconsequential changes in intravascular
      volume and electrolyte disturbances. Serious electrolyte disturbances have been
      associated with oral sodium phosphate administration in patients in whom sodium
      phosphate is contraindicated or should be use with caution (the elderly and those
      with bowel obstructions, small intestinal disorders, poor gut motilderly and
      those with bowel obstructions, small intestinal disorders, poor gut motility,
      renal insufficiency, cardiovascular disease or taking concomitant medication) or
      in patients ingesting more than the recommended dosage. Changes in the colonic
      mucosa have been reported in patients treated with oral sodium phosphate
      solution; however, the exact role of this agent in the appearance of these
      changes has not been fully clarified. The tolerability profile of oral sodium
      phosphate solution was similar to, or significantly better than, that of PEG or
      other colorectal cleansing regimens. Oral sodium phosphate solution was generally
      significantly more acceptable than PEG or other colorectal cleansing regimens.
      Oral sodium phosphate solution had similar tolerability, but was considered to be
      more acceptable than commercially available oral sodium phosphate tablets prior
      to colonoscopy (data from one study).

PMID- 15257634
TI  - Battling red tape.

PMID- 15257635
TI  - Good for your heart but bad for your baby? Revised guidelines for fish
      consumption in pregnancy.

PMID- 15257636
TI  - Avian influenza and planning for pandemics.

PMID- 15257637
TI  - Managing medical indemnity: must we choose between quality assurance and risk
      management?

PMID- 15257638
TI  - The way forward: the International Primary Care Respiratory Group 2nd World
      Conference, Melbourne, 19-22 February 2004.

PMID- 15257639
TI  - How people with chronic illnesses view their care in general practice: a
      qualitative study.
AB  - OBJECTIVES: To explore the perceptions of patients with chronic conditions about
      the nature and quality of their care in general practice. DESIGN: Qualitative
      study using focus group methods conducted 1 June to 30 November 2002.
      PARTICIPANTS AND SETTING: 76 consumers in 12 focus groups in New South Wales and
      South Australia. MAIN OUTCOME MEASURES: Recurring issues and themes on care
      received in general practice. RESULTS: Three groups of priorities emerged. One
      centred on the quality of doctors, including technical competence, interpersonal
      skills, time for the patient in the consultation and continuity of care. A second
      concerned the role of patients and consumer organisations, with patients wanting
      (i) recognition of their knowledge about their condition and self-management, and
      (ii) for GPs to develop closer links with consumer organisations and inform
      patients about them. The third focused on the practice team and the importance of
      practice nurses and receptionists. CONCLUSION: GPs should consider the amount of
      time they spend with chronically ill patients, and their interpersonal skills and
      understanding of patients' needs. They need to be better informed about the
      benefits of patient self-management and consumer organisations, and to
      incorporate them into their care. They also need to review how their practice
      nurses and receptionists can maximise the care of patients.

PMID- 15257641
TI  - Clinical psychology in general practice: a cohort study.
AB  - OBJECTIVE: To evaluate whether a collaborative model of mental healthcare
      involving general practitioners and clinical psychologists benefits patients with
      common mental disorders in primary care. DESIGN AND PARTICIPANTS: Cohort study of
      276 general practice patients with mental health problems receiving collaborative
      treatment from clinical psychologists and GPs compared with a normative sample of
      198 patients attending the same general practice surgeries. SETTING: Nine general
      practices in three regional cities (Bathurst, Armidale and Ballarat) and two
      single-doctor practices in two rural and remote townships (Rylstone and Trundle).
      Data were collected in Bathurst, Rylstone and Trundle during 2001 and 2002 and in
      Ballarat and Armidale in 2002. INTERVENTION: Full assessment, case formulation
      and "focussed psychological interventions" relevant to the patient's condition.
      MAIN OUTCOME MEASURES: Level of psychological dysfunction assessed before and
      after the intervention, using the DASS (Depression, Anxiety and Stress Scales),
      GHQ (General Health Questionnaire) and GWBI (General Well Being Index) scales.
      RESULTS: After the intervention, average scores in the treatment group decreased
      significantly (P < 0.001) on all DASS and GHQ measures and increased on the GWBI,
      indicating a positive change in the patients' mental health. The follow-up scores
      of the treatment and normative groups did not differ significantly on any of
      these measures. CONCLUSION: Preliminary findings suggest that collaborative care
      involving GPs and clinical psychologists provides significant gains in patients'
      mental health.

PMID- 15257642
TI  - Barriers to diagnosing and managing heart failure in primary care.
AB  - OBJECTIVE: To explore potential barriers to the optimal diagnosis and management
      of heart failure in primary care. DESIGN AND SETTING: Qualitative study involving
      semi-structured focus groups or telephone interviews with general practitioners,
      in three urban and one rural Division of General Practice with above-average
      elderly resident populations, conducted between 1 April and 31 July 2002.
      PARTICIPANTS: 31 self-selected GPs who responded to a general invitation and four
      GPs who were personally invited to participate in the study. MAIN OUTCOME
      MEASURES: Issues identified by GPs as barriers and GPs' ratings of their
      importance. RESULTS: GPs reported that most of the difficulties in accurately
      diagnosing heart failure were associated with masking of the disease by other
      conditions and the lack of specificity of the symptoms, particularly in the early
      stages. They felt that echocardiograms can be difficult to access, were of
      unclear benefit and may not be warranted in obvious cases. Concerns about
      possible side effects and reliance on other forms of therapy were common reasons
      for the suboptimal use of angiotensin-converting enzyme inhibitors. Underuse of
      beta-blockers was associated mainly with concerns about side effects,
      contraindications and comorbidities, and a lack of experience with initiating
      therapy, particularly in community settings. CONCLUSIONS: This study identified
      specific barriers to GPs implementing evidence-based recommendations in managing
      heart failure. Tailored strategies that address the practical concerns of GPs
      about applying research evidence in the primary care setting and that facilitate
      better linkages between GPs and specialists are needed.

PMID- 15257643
TI  - Secondary prevention of overweight in primary school children: what place for
      general practice?
AB  - At least a quarter of primary school children in Australia are overweight or
      obese; the long-term impacts are likely to include chronic morbidity and loss of
      life-years. Universal preventive strategies have so far had limited
      effectiveness, while secondary and tertiary referral services would be
      overwhelmed if they attempted to systematically manage a problem with such high
      prevalence. Primary care services could play an important role in secondary
      prevention of overweight and mild obesity in children. While reports of child
      obesity research have burgeoned since 1995, effectiveness trials of primary care
      interventions in primary-school-aged children have been neglected. Randomised
      controlled trials of a primary care approach, although challenging, are essential
      to determine whether it does more good than harm.

PMID- 15257644
TI  - Ciprofloxacin in the treatment of chronic suppurative otitis media.

PMID- 15257645
TI  - The evolution of the general practice workforce in Australia, 1991-2003.
AB  - OBJECTIVE: To examine changes between 1991 and 2003 in the characteristics of
      active recognised general practitioners in Australia. DESIGN: We compared self
      reported GP characteristics from the 1990-91 Australian Morbidity and Treatment
      Survey (AMTS) with those from the 1999 and 2003 Bettering the Evaluation and Care
      of Health (BEACH) surveys, after standardisation for age and sex to the
      respective sample frames. AMTS and BEACH are cross-sectional, paper-based,
      national surveys. PARTICIPANTS: Three random samples of 473 (1990-91), 980 (1998
      99) and 1008 (2002-03) GPs who had claimed at least 1500 A1 (ie, general
      practice) Medicare items in the preceding year (in the AMTS) or 375 general
      practice Medicare items in the preceding 3 months (in the BEACH surveys). MAIN
      OUTCOME MEASURES: Changes in distribution of GP sex, GP age, number of sessions
      per week, practice size and location, country of graduation, and postgraduate
      training. RESULTS: Between 1991 and 2003, the proportion of female GPs rose from
      19.3% to 35.2%; GPs aged < 35 years dropped from 22.3% to 10.0%, and those aged
      >or= 55 years increased from 21.4% to 31.6%. Between 1999 and 2003, the
      proportion of male GPs working < 6 sessions/week increased from 6.1% to 11.4%,
      while the proportion working >or= 11 sessions/week fell from 23.8% to 17.1%.
      Between 1991 and 2003, the proportion of solo practitioners nearly halved (25.5%
      v 13.7%); the proportion of GPs in practices of >or= 4 partners increased from
      34.3% to 59.8%; the proportion of Australian graduates fell from 81.4% to 72.2%;
      and the proportion of graduates from Asia and Africa increased. Over the same
      period, the proportion of GPs with Fellowship of the Royal Australian College of
      General Practitioners more than doubled (17.8% v 36.4%). All of these differences
      were statistically significant (P < 0.001). CONCLUSION: Changes in
      characteristics of the practising GP population will affect consultative services
      and the balance between supply and demand for these services. These changes
      should be considered in future workforce planning.

PMID- 15257646
TI  - Still the doctor - by a country mile! Preferences for health services in two
      country towns in north-west New South Wales.
AB  - OBJECTIVE: To evaluate whether rural consumer preferences for health services
      have changed over time or vary across communities with different models of health
      service delivery. DESIGN: Questionnaire survey replicating a 1989 study, with
      ranking of seven different healthcare services. PARTICIPANTS AND SETTING: Adult
      occupants from a 20% sample of private residences, in towns and on farms, in the
      rural shires of Bogan and Warren in north-west New South Wales. The survey was
      conducted in September 2002. MAIN OUTCOME MEASURES: Rank order of preferences for
      different healthcare services; preference structure intervals showing relative
      "distance" between preferences. RESULTS: Response rates were 68% (Nyngan town),
      78% (Nyngan farms) and 59% (Warren town). The doctor was the most valued health
      service in rural communities, followed by the hospital. These preferences
      occurred regardless of age, sex or place of residence, persisted over time, and
      were similar for residents of towns with different models of healthcare service
      provision. CONCLUSIONS: Rural people, both in towns and on farms, rate acute
      primary healthcare services provided by the doctor and hospital as the two most
      important services. These preferences have not changed substantially after a
      decade of restructuring rural health services and reorienting them towards a
      primary healthcare approach. The stability of rural consumer preferences may
      reflect a bias towards the status quo.

PMID- 15257647
TI  - Nothing new under the hard Bourke sun: international medical graduates,
      conditional medical registration and areas of need.

PMID- 15257648
TI  - I want to work and have a life as well.
AB  - How one rural general practice retains its workforce.

PMID- 15257649
TI  - How should GPs be paid?
AB  - We need evidence that can underpin fundamental change.

PMID- 15257650
TI  - Determinants of GP billing in Australia: content and time.
AB  - OBJECTIVE: To examine relations between consultation length and content, and
      general practitioner choice of claiming level B or C when billing consultations >
      20 minutes through Medicare. DESIGN AND SETTING: A secondary analysis from a
      cross-sectional national general practice survey (1 April 2000 to 31 March 2003)
      of 101 112 consultations with 2811 GPs, comparing level B consultations <or= 20
      minutes with consultations > 20 minutes (claimed as level B or C), and
      consultations > 20 minutes claimed as level C with those claimed as level B. MAIN
      OUTCOME MEASURES: Consultation length, encounter, patient characteristics;
      number, type of problems managed; type and frequency of treatments provided in
      relation to consultation level charged. RESULTS: There were 80 476 level B
      consultations <or= 20 minutes and 14 893 > 20 minutes claimed as level B or C
      (5725 [38.4%] level B; 9168 [61.5%] level C). Longer level B+C consultations
      differed from shorter level B consultations in patient sex, Department of
      Veterans' Affairs card status, and new-patient status, and involved more reasons
      for encounter, problems managed, chronic problems, clinical treatments,
      therapeutic procedures, referrals and pathology and imaging orders. Longer
      consultations claimed as level C were significantly longer (0.9 minutes) than
      those claimed as level B and involved more reasons for encounter, problems
      managed (particularly new, chronic, psychosocial and gynaecological) and more
      clinical treatments. CONCLUSIONS: Patient characteristics and consultation
      content differ at longer consultations. Consultations charged as level C are more
      complex than those charged as level B. GPs use both time and content when
      choosing item number, rather than relying only on specified time thresholds. This
      has implications for future restructuring of MBS attendance items.

PMID- 15257651
TI  - How general practice is funded in New Zealand.

PMID- 15257652
TI  - How general practice is funded in the United Kingdom.

PMID- 15257653
TI  - How general practice is funded in The Netherlands.

PMID- 15257654
TI  - How family physicians are funded in Canada.

PMID- 15257655
TI  - How family physicians are funded in the United States.

PMID- 15257656
TI  - Factors influencing billing status in general practice.

PMID- 15257657
TI  - Implanon and medical indemnity: a case study of risk management using the
      Australian standard.
AB  - The contraceptive implant Implanon (Organon) was introduced in Australia in May
      2001, and in the next 18 months was associated with an unprecedented number of
      adverse incident reports to medical indemnity insurers, including almost 100
      unintended pregnancies. The medical indemnity insurer, MDA National, responded to
      this by applying the Australian and New Zealand Standard for Risk Management
      (AS/NZS 4360: 1999) in two stages. The first stage was to contain potential costs
      by moving the treatment into the general practice procedural category, resulting
      in a one-year moratorium on its use for most general practitioner members
      (prudential risk management). The second stage was to manage the clinical risk by
      developing strategies to reduce identified risks associated with the procedure.
      The Royal Australian College of General Practitioners (RACGP) was enlisted to
      develop guidelines for use of Implanon, with a consent form and checklists for
      doctors and patients, enabling MDA National to reinstate the treatment to the
      general practice non-procedural category. This case demonstrates the need for
      early risk assessment and development of risk-management tools for new treatments
      and devices, a role that is appropriate for the RACGP.

PMID- 15257658
TI  - The NRF-1/alpha-PAL transcription factor regulates human E2F6 promoter activity.
AB  - E2F6 is widely expressed in human tissues and cell lines. Recent studies have
      demonstrated its involvement in developmental patterning and in the regulation of
      various genes implicated in chromatin remodelling. Despite a growing number of
      studies, nothing is really known concerning the E2F6 expression regulation. To
      understand how cells control E2F6 expression, we analysed the activity of the
      previously cloned promoter region of the human E2F6 gene. DNase I footprinting,
      gel electrophoreticmobility shift, transient transfection and site-directed
      mutagenesis experiments allowed the identification of two functional NRF-1/alpha
      PAL (nuclear respiratory factor-1/alpha-palindrome-binding protein)-binding sites
      within the human E2F6 core promoter region, which are conserved in the mouse and
      rat E2F6 promoter region. Moreover, ChIP (chromatin immunoprecipitation) analysis
      demonstrated that overexpressed NRF-1/alpha-PAL is associated in vivo with the
      E2F6 promoter. Furthermore, overexpression of full-length NRF-1/alpha-PAL
      enhanced E2F6 promoter activity, whereas expression of its dominant-negative form
      reduced the promoter activity. Our results indicate that NRF-1/alpha-PAL is
      implicated in the regulation of basal E2F6 gene expression.

PMID- 15257659
TI  - Requirement of different mitochondrial targeting sequences of the yeast
      mitochondrial transcription factor Mtf1p when synthesized in alternative
      translation systems.
AB  - Mitochondrial (mt) translocation of the nuclearly encoded mt transcription factor
      Mtf1p appears to occur independent of a cleavable presequence, mt receptor, mt
      membrane potential or ATP [Biswas and Getz (2002) J. Biol. Chem. 277, 45704
      45714]. To understand further the import strategy of Mtf1p, we investigated the
      import of the wild-type and N-terminal-truncated Mtf1p mutants synthesized in two
      different in vitro translation systems. These Mtf1p derivatives were generated
      either in the RRL (rabbit reticulocyte lysate) or in the WGE (wheat germ extract)
      translation system. Under the in vitro import conditions, the RRL-synthesized
      full-length Mtf1p but not the N-terminal-truncated Mtf1p product was efficiently
      imported into mitochondria, suggesting that the N-terminal sequence is important
      for its import. On the other hand, when these Mtf1p products were generated in
      the WGE system, surprisingly, the N-terminal-truncated products, but not the full
      length protein, were effectively translocated into mitochondria. Despite these
      differences between the translation systems, in both cases, import occurs at a
      low temperature and has no requirement for a trypsin-sensitive mt receptor, mt
      membrane potential or ATP hydrolysis. Together, these observations suggest that,
      in the presence of certain cytoplasmic factors (derived from either RRL or WGE),
      Mtf1p is capable of using alternative import signals present in different regions
      of the protein. This appears to be the first example of usage of different
      targeting sequences for the transport of a single mt protein into the mt matrix.

PMID- 15257661
TI  - Annotation: Deconstructing the attention deficit in fragile X syndrome: a
      developmental neuropsychological approach.
AB  - BACKGROUND: Fragile X syndrome is one of the world's leading hereditary causes of
      developmental delay in males. The past decade has witnessed an explosion of
      research that has begun to unravel the condition at its various levels: from the
      genetic and brain levels to the cognitive level, and then to the environmental
      and behavioural levels. Our aim in this review is to attempt to integrate some of
      the extensive body of knowledge to move the research a step closer to
      understanding how the dynamics of atypical development can influence the specific
      cognitive and behavioural end-states frequently observed in children and
      adolescents with fragile X syndrome. METHODS: We conducted a review of the
      current neuropsychological and neuropsychiatric approaches that have attempted to
      delineate the pattern of 'spared' and 'impaired' functions associated with the
      phenotype. RESULTS: The profile of findings suggests that fragile X syndrome
      should not be viewed merely as a catalogue of spared and impaired cognitive
      functions or modules. Instead, there appears to be a process of almost gradual
      modularisation whereby cognitive mechanisms become domain specific as a function
      of development itself (Karmiloff-Smith, 1992). The results of a decade of intense
      research point towards an early weakness in one or more components of executive
      control rather than single, static higher-level deficits (e.g., spatial
      cognition, speech processing). This weakness affects both the development of more
      complex functions and current performance. CONCLUSIONS: The prevailing tendency
      to interpret developmental disorders in terms of fixed damage to distinct modular
      functions needs to be reconsidered. We offer this review as an example of an
      alternative approach, attempting to identify an initial deficit and its
      consequences for the course of development. Through better definition of the
      cognitive and behavioural phenotype, in combination with current progress in
      brain imaging techniques and molecular studies, the next decade should continue
      to hold exciting promise for fragile X syndrome and other neurodevelopmental
      disorders.

PMID- 15257662
TI  - Effects of music therapy for children and adolescents with psychopathology: a
      meta-analysis.
AB  - BACKGROUND: The objectives of this review were to examine the overall efficacy of
      music therapy for children and adolescents with psychopathology, and to examine
      how the size of the effect of music therapy is influenced by the type of
      pathology, client's age, music therapy approach, and type of outcome. METHOD:
      Eleven studies were included for analysis, which resulted in a total of 188
      subjects for the meta-analysis. Effect sizes from these studies were combined,
      with weighting for sample size, and their distribution was examined. RESULTS:
      After exclusion of an extreme positive outlying value, the analysis revealed that
      music therapy has a medium to large positive effect (ES =.61) on clinically
      relevant outcomes that was statistically highly significant (p <.001) and
      statistically homogeneous. No evidence of a publication bias was identified.
      Effects tended to be greater for behavioural and developmental disorders than for
      emotional disorders; greater for eclectic, psychodynamic, and humanistic
      approaches than for behavioural models; and greater for behavioural and
      developmental outcomes than for social skills and self-concept. CONCLUSIONS:
      Implications for clinical practice and research are discussed.

PMID- 15257664
TI  - Cognitive appraisals in young people with obsessive-compulsive disorder.
AB  - BACKGROUND: A number of cognitive appraisals have been identified as important in
      the manifestation of obsessive-compulsive disorder (OCD) in adults. There have,
      however, been few attempts to explore these cognitive appraisals in clinical
      groups of young people. METHOD: This study compared young people aged between 11
      and 18 years with OCD (N = 28), young people with other types of anxiety
      disorders (N = 28) and a non-clinical group (N = 62) on three questionnaire
      measures of cognitive appraisals. These were inflated responsibility
      (Responsibility Attitude Scale; Salkovskis et al., 2000), thought-action fusion-
      likelihood other (Thought-Action Fusion Scale; Shafran, Thordarson & Rachman,
      1996) and perfectionism (Multidimensional Perfectionism Scale; Frost, Marten,
      Luhart & Rosenblate, 1990). RESULTS: The young people with OCD had significantly
      higher scores on inflated responsibility, thought-action fusion--(likelihood
      other), and one aspect of perfectionism, concern over mistakes, than the other
      groups. In addition, inflated responsibility independently predicted OCD symptom
      severity. CONCLUSIONS: The results generally support a downward extension of the
      cognitive appraisals held by adults with OCD to young people with the disorder.
      Some of the results, however, raise issues about potential developmental shifts
      in cognitive appraisals. The findings are discussed in relation to implications
      for the cognitive model of OCD and cognitive behavioural therapy for young people
      with OCD.

PMID- 15257663
TI  - Postpartum maternal moods and infant size predict performance on a national high
      school entrance examination.
AB  - BACKGROUND: In an earlier series of studies, we documented the effects of feeding
      practices and postnatal maternal mood on the growth and development of 226
      Barbadian children during the first few months of life. In this report, we extend
      our earlier studies by examining predictive relationships between infant size,
      feeding practices and postpartum maternal moods and scores on a national high
      school examination, the Common Entrance Examination (CEE), at 11 to 12 years of
      age. METHODS: Feeding practices, anthropometry, and maternal moods, using Zung
      depression and anxiety scales and a morale scale, were assessed at 7 weeks (n =
      158), 3 months (n = 168), and 6 months (n = 209) postpartum. Background variables
      including sociodemographic and home environmental factors were also assessed
      during infancy. CEE scores on 169 of the children in the original study were
      obtained from the Ministry of Education of Barbados. RESULTS: In our sample of 86
      boys and 83 girls, we found that reduced infant lengths and weights at 3 and 6
      months of age were predictive of lower CEE, especially math scores. Children who
      were smaller at these early ages had significantly lower scores on the
      examination than did larger children. Postpartum maternal moods, including
      reports of despair and anxiety, were also found to be significant predictors of
      lower CEE scores, especially English scores. However, breast-feeding and other
      feeding practices were not directly associated with the CEE scores. Background
      variables, which significantly predicted lower CEE scores, included young
      maternal age at the time of her first pregnancy, more children in the home, less
      maternal education, and fewer home conveniences. Significant associations between
      infant anthropometry, maternal moods and CEE scores were all significant even
      when these background variables were controlled for. CONCLUSIONS: These findings
      have important implications for developing interventions early in life to improve
      academic test scores and future opportunities available to children in this
      setting.

PMID- 15257665
TI  - Contributions of phonological memory, language comprehension and hearing to the
      expressive language of adolescents and young adults with Down syndrome.
AB  - BACKGROUND: Expressive language constitutes a major challenge to the development
      of individuals with Down syndrome. This paper investigates the relationships
      between expressive language abilities, language comprehension and the deficits in
      verbal short-term memory and hearing which are also associated with the syndrome.
      METHODS: Tests of nonverbal ability, expressive language, verbal short-term
      memory, visuo-spatial memory, language comprehension and hearing were
      administered. RESULTS: Phonological memory, measured by nonword repetition, was
      significantly correlated with expressive language abilities measured by MLU and
      sentence recall. Adjusting for word repetition skills did not reduce this
      correlation, suggesting that the relationship did not depend on the fact that
      both tests required spoken output. Hearing did not contribute significantly to
      expressive language scores of participants who provided an intelligible
      narrative. However, level of hearing loss as well as other language and memory
      measures did differentiate these participants from those who were unable to
      produce an intelligible narrative. CONCLUSION: Phonological memory was closely
      associated with the expressive language abilities of individuals with Down
      syndrome. Hearing loss appeared to be less closely related except that
      individuals with uncorrected mild to moderate hearing loss had difficulty with
      the narrative task. Further research is necessary to establish the nature of
      these relationships.

PMID- 15257666
TI  - Theory-of-mind development in oral deaf children with cochlear implants or
      conventional hearing aids.
AB  - BACKGROUND: In the context of the established finding that theory-of-mind (ToM)
      growth is seriously delayed in late-signing deaf children, and some evidence of
      equivalent delays in those learning speech with conventional hearing aids, this
      study's novel contribution was to explore ToM development in deaf children with
      cochlear implants. Implants can substantially boost auditory acuity and rates of
      language growth. Despite the implant, there are often problems socialising with
      hearing peers and some language difficulties, lending special theoretical
      interest to the present comparative design. METHODS: A total of 52 children aged
      4 to 12 years took a battery of false belief tests of ToM. There were 26 oral
      deaf children, half with implants and half with hearing aids, evenly divided
      between oral-only versus sign-plus-oral schools. Comparison groups of age-matched
      high-functioning children with autism and younger hearing children were also
      included. RESULTS: No significant ToM differences emerged between deaf children
      with implants and those with hearing aids, nor between those in oral-only versus
      sign-plus-oral schools. Nor did the deaf children perform any better on the ToM
      tasks than their age peers with autism. Hearing preschoolers scored significantly
      higher than all other groups. For the deaf and the autistic children, as well as
      the preschoolers, rate of language development and verbal maturity significantly
      predicted variability in ToM, over and above chronological age. CONCLUSIONS: The
      finding that deaf children with cochlear implants are as delayed in ToM
      development as children with autism and their deaf peers with hearing aids or
      late sign language highlights the likely significance of peer interaction and
      early fluent communication with peers and family, whether in sign or in speech,
      in order to optimally facilitate the growth of social cognition and language.

PMID- 15257667
TI  - Speech-in-noise perception in high-functioning individuals with autism or
      Asperger's syndrome.
AB  - BACKGROUND: High-functioning individuals with autism (HFA) or Asperger's syndrome
      (AS) commonly report difficulties understanding speech in situations where there
      is background speech or noise. The objective of this study was threefold: (1) to
      verify the validity of these reports; (2) to quantify the difficulties
      experienced; and (3) to propose possible mechanisms to explain the perceptual
      deficits described. METHOD: Speech-in-noise perception abilities were measured
      using speech reception thresholds (SRTs), defined as the speech-to-noise ratio
      (SNR) at which approximately 50% of the speech is correctly identified. SRTs were
      measured for 11 individuals with HFA/AS and 9 age/IQ-matched normal-hearing
      control subjects, using an adaptive procedure, in a non-reverberant sound
      attenuating chamber. The speech materials were standardised lists of everyday
      sentences spoken by a British male speaker. The background sounds were: (1) a
      single female talker; (2) a steady speech-shaped noise; (3) a speech-shaped noise
      with temporal dips; (4) a steady speech-shaped noise with regularly spaced
      spectral dips; and (5) a speech-shaped noise with temporal and spectral dips.
      RESULTS: SRTs for the HFA/AS group were generally higher (worse) than those for
      the controls, across the five background sounds. A statistically significant
      difference in SRTs between the subject groups was found only for those background
      sounds that contained temporal or spectro-temporal dips. SRTs for the HFA/AS
      individuals were 2 to 3.5 dB higher than for the controls, equivalent to a
      substantial decrease in speech recognition. Expressed another way, the HFA/AS
      individuals required a higher SNR, whenever there were temporal dips in the
      background sound, to perform at the same level as the controls. CONCLUSIONS: The
      results suggest that the speech-in-noise perception difficulties experienced by
      individuals with autism may be due, in part, to a reduced ability to integrate
      information from glimpses present in the temporal dips in the noise.

PMID- 15257668
TI  - Impaired disengagement of attention in young children with autism.
AB  - BACKGROUND: The present study examined the disengage and shift operations of
      visual attention in young children with autism. METHODS: For this purpose, we
      used a simple visual orienting task that is thought to engage attention
      automatically. Once attention was first engaged on a central fixation stimulus, a
      second stimulus was presented on either side, either simultaneously or
      successively. Latency to begin an eye movement to the peripheral stimulus served
      as the main dependent measure. The two stimulus conditions (simultaneous and
      successive) provided independent measures of disengaging and shifting attention,
      respectively. Performance of children with autism was compared to that of
      children with Down syndrome and a normal group. RESULTS: The main finding was
      that relative to both comparison groups, children with autism had marked
      difficulty in disengaging attention. Indeed, on 20% of trials they remained
      fixated on the first of two competing stimuli for the entire 8-second trial
      duration. Evidence is also provided for a more subtle problem in executing rapid
      shifts of attention. CONCLUSIONS: Our findings on disengagement in autism
      parallel those reported in normal 2-month-olds, in whom attention has been
      described as 'obligatory'. Discussion focuses on the potential role of general
      versus domain-specific processes in producing some of the core features of
      autism.

PMID- 15257669
TI  - Autism and attachment: a meta-analytic review.
AB  - METHOD: Sixteen studies on attachment in children with autism were reviewed, and
      ten studies with data on observed attachment security (N = 287) were included in
      a quantitative meta-analysis. RESULTS: Despite the impairments of children with
      autism in reciprocal social interaction, the majority of the studies found
      evidence for attachment behaviours in these children. In four samples using the
      Strange Situation procedure the average percentage of secure attachments amounted
      to 53% (n = 72). Meta-analytic results showed that children with autism were
      significantly less securely attached to their parents than comparison children,
      and the combined effect size for this difference was moderate (r =.24). Children
      with autism displayed less attachment security than comparisons without autism,
      but this difference disappeared in samples with children with higher mental
      development, and in samples in which autism was mixed with less severe symptoms
      of autistic spectrum disorders. CONCLUSIONS: It is concluded that attachment
      security is compatible with autism, and can be assessed with Strange Situation
      type of procedures. The co-morbidity of autism and mental retardation appears to
      be associated with attachment insecurity.

PMID- 15257670
TI  - Comparison of ADHD symptom subtypes as source-specific syndromes.
AB  - BACKGROUND: This study examines differences between the three subtypes of
      attention-deficit/hyperactivity disorder (ADHD), inattentive (I), hyperactive
      impulsive (H), and combined (C), in a heterogeneous sample of 248 boys (ages 6 to
      10 years) with emotional and behavioral problems who were recruited for
      participation in a diagnostic study. METHOD: The boys and their mothers
      participated in an extensive evaluation that involved multiple assessments of
      cognitive, behavioral, academic, and family functioning. ADHD subtypes were
      defined on the basis of teacher alone, mother alone, and mother/teacher ratings
      of DSM-IV symptoms. RESULTS: Results indicated ADHD symptom groups showed a
      differential pattern of impairment socially (H,C>I) and cognitively (I,C>H). The
      C and H groups were the most and least impaired overall, respectively, and all
      subtypes were differentiated from the nonADHD clinical control or NONE (N) group
      in a manner consistent with the primary findings. External validation of group
      differences was limited, and there were marked inconsistencies in the pattern of
      findings depending on how groups were defined. For the most part, although the
      mother/teacher grouping strategy (compared with either alone) captured a greater
      diversity of differences between subtypes, it also obscured some. CONCLUSIONS:
      Observed findings are consistent with the notion that mothers and teachers
      interpret symptom statements in terms of behaviors that are most relevant for
      their daily concerns.

PMID- 15257671
TI  - Psychopathology in female juvenile offenders.
AB  - BACKGROUND: The aim was to document the spectrum of present and lifetime
      psychological disorders in female juvenile offenders, and to examine the
      relations between mental health status and socio-demographic, family and trauma
      variables. METHOD: One hundred juvenile offenders were matched with a comparison
      group of 100 females on age and socioeconomic status (SES). Psychological
      profiles and trauma histories of both groups were assessed using the Schedule for
      Affective Disorders and Schizophrenia for School-Age Children--Present and
      Lifetime Version (K-SADS-PL) and family functioning was assessed with the Family
      Adaptability and Cohesion Scale II (FACES II) self-report measure. RESULTS: Rates
      of psychopathology were higher for offenders than non-offenders (p <.001), with
      particularly high levels of conduct disorder (91% v.1%, p <.001), substance abuse
      disorders (85% v. 5%, p <.001), depression (55% v. 25%, p <.001) and
      posttraumatic stress disorder (37% v. 4%, p <.001). In the offenders, 78% met the
      criteria for three or more diagnoses. The number of psychiatric diagnoses was the
      most significant factor associated with offender status (OR = 21.26, p <.001).
      CONCLUSIONS: There is a high prevalence of psychological disorder in females in
      juvenile justice custody and this has a very strong association with offender
      status. Because these co-morbid disorders are treatable, there is a clear
      opportunity to intervene to decrease psychological distress.

PMID- 15257672
TI  - The prediction of disruptive behaviour disorders in an urban community sample:
      the contribution of person-centred analyses.
AB  - BACKGROUND: Variable- and person-centred analyses were used to examine prediction
      of middle childhood behaviour problems from earlier child and family measures.
      METHOD: A community sample of 164 families, initially recruited at antenatal
      clinics at two South London practices, was assessed for children's behaviour
      problems and cognitive ability, maternal mental health, and the family
      environment when the children were 4 years old. At age 11, children, mothers, and
      teachers reported the child's disruptive behaviour, and mothers and children were
      interviewed to identify cases of disruptive behaviour disorders (DBD). RESULTS:
      Neither social class nor ethnicity predicted the child's disruptive behaviour at
      age 11. Rather, path analyses and logistic regression analyses drew attention to
      early behavioural problems, maternal mental health and the child's cognitive
      ability at 4 as predictors of disruptive behaviour at age 11. Cluster analysis
      extended these findings by identifying two distinct pathways to disruptive
      symptoms and disorder. In one subgroup children who showed intellectual
      difficulties at 4 had become disruptive by 11. In a second subgroup mothers and
      children both showed psychological problems when the child was 4, and the
      children were disruptive at age 11. The person-centred approach also revealed a
      high-functioning group of cognitively able 4-year-olds in supportive
      environments, at especially low risk for DBD. CONCLUSIONS: Combining variable-
      and person-centred analytic approaches can aid prediction of children's problems,
      draw attention to pertinent developmental pathways, and help integrate data from
      multiple informants.

PMID- 15257673
TI  - Parent-child dyadic mutuality and child behavior problems: an investigation of
      gene-environment processes.
AB  - BACKGROUND: Parent-child mutuality is comprised of emotional reciprocity, co
      responsiveness, and cooperation, which together represent aspects of co
      regulation of emotion and behavior that may be important in the etiology of
      children's behavior problems. Furthermore, individual differences in children's
      mutuality and behavior problems involve transactions between genetic and
      environmental influences. Behavioral genetic designs are useful for elucidating
      these processes. METHODS: The sample included 396 children in adoptive families
      (53% female, age M = 8.16 years), of whom 244 were siblings (122 pairs). All of
      the siblings were genetically unrelated. In some families, one child was adopted
      but the other child was a biological child of the adoptive parents. We observed
      mother-child dyadic mutuality (a composite score including responsiveness,
      interaction reciprocity, and cooperation) during videotaped in-home observations.
      In addition, child behavior problems were assessed and represented as a composite
      score including observers' ratings of noncompliance, and parents' ratings of
      aggression and conduct problems. RESULTS: Greater mutuality was associated with
      lower levels of child behavior problems, both between families and within
      families (i.e., sibling differences). The sibling intra-class correlation for
      mutuality with the same parent was near zero in this sample of genetically
      unrelated siblings. The correlation between child behavior problems and dyadic
      mutuality did not vary as a function of mother-child genetic similarity.
      CONCLUSIONS: Mother-child mutuality is child specific within families, a finding
      that is consistent with theories regarding bi-directional parent and child
      effects in socialization. In addition, there was no evidence of passive gene
      environment correlation, suggesting that the link between lower levels of
      maternal mutuality and higher levels of child behavior problems is not only
      reflecting overlapping genetic influences on parent and child behavior.

PMID- 15257679
TI  - The clinical outcomes of neonatal and childhood stroke: review of the literature
      and implications for future research.
AB  - A detailed assessment of clinical outcomes after ischemic stroke in childhood is
      necessary to evaluate prognostic factors. Previous studies are difficult to
      compare because of differences in test instruments, study design, heterogeneity
      of cohorts and number of included cases. Depending on neurodevelopmental
      assessment methods, major and subtle/minor disabilities, especially in infants,
      may not have been detected. Most outcome studies reveal only limited information
      about behavioral changes and quality of life in children with ischemic stroke.
      Thus the assumption that children make a better recovery from stroke than adults
      due to the immature brain's capacity to reorganize function is not evidence
      based. We systematically review the current literature with regard to the
      neurological and psychosocial development of affected children as well as their
      quality of life. Implications for future research strategies follow the review to
      encourage further clinical study of the neurobehavioral trajectory of childhood
      stroke.

PMID- 15257680
TI  - Primary progressive multiple sclerosis: clinical and paraclinical characteristics
      with application of the new diagnostic criteria.
AB  - The aim of our study was to analyse clinical and paraclinical characteristics of
      patients with multiple sclerosis (MS) with previous diagnosis of primary
      progressive (PP) MS according to the Poser's criteria and further investigate if
      they fulfil the McDonald's diagnostic criteria for this disorder. A total of 561
      MS patients were registered in the database at the Institute of Neurology,
      Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with
      previous diagnosis of PPMS were analysed retrospectively. Male/female ratio was
      1.3:1 and mean age at onset 33.2 years. Most frequent at onset were pyramidal (in
      73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had
      greater than or equal to nine brain magnetic resonance imaging (MRI) lesions.
      Intrathecal oligoclonal immunoglobulin G (IgG) was detected in 96.7% and
      prolonged visual evoked potentials (VEP) P100 latency in 82.4% of patients. Of
      the total study group of 561 patients, 10.2% fulfilled the recently recommended
      McDonald's diagnostic criteria for the diagnosis of PPMS. Our findings further
      support the significance of the brain/spinal cord MRI, cerebrospinal fluid and
      VEP findings for precise diagnostic assessment in patients with suspected PP form
      of MS.

PMID- 15257681
TI  - Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis.
AB  - The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2
      have been strongly implicated in disease pathogenesis in experimental autoimmune
      encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on
      the CCL2-CCR2 axis are scarce in MS. We studied the expression of CCR2 on
      leukocytes in blood and cerebrospinal fluid (CSF) from patients with
      monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF
      from these patients. Results were compared with the results in non-inflammatory
      neurological controls and were correlated with other parameters (magnetic
      resonance imaging and CSF data). Our findings suggest a limited role for
      CCL2/CCR2 in early active MS.

PMID- 15257682
TI  - Improvement in quality of life in patients with advanced Parkinson's disease
      following bilateral deep-brain stimulation in subthalamic nucleus.
AB  - In this article we investigate the changes observed in the scales that quantify
      the quality of life (PDQ-39) in patients that have already completed 1 and 2
      years of bilateral subthalamic stimulation (DBS-STN). Fourteen patients were
      evaluated 1 year after DBS-STN; the evaluation was repeated on 11 of them, 2
      years after surgery. All of them suffered from Parkinson's disease with a 14.3
      (+/-5.7) years history of motor complications. Patients were selected according
      to CAPSIT criteria. All of them were implanted bilateral electrodes in the
      subthalamic nucleus. The parameters applied were UPDRS II, UPDRS III, PDQ-39, and
      the scale of quality of life for caregivers (SQLC). Scorings in motor scales
      (UPDRS III) improved 45% in relation to the first year, and 48% in relation to
      the second year (P < 0.001). Patient's quality of life (PDQ-39 summary index)
      improvement was 62% 2 years after surgery (P < 0.001), and caregivers' quality of
      life improvement was 68% (P = 0.002) by the same time. DBS-STN is a therapy that
      efficiently improves the quality of life of selected patients with Parkinson's
      disease. This improvement is still present 2 years after surgery and has a
      positive impact on caregivers quality of life.

PMID- 15257683
TI  - beta2-microglobulin serum level is not a marker of disease activity in multiple
      sclerosis.
AB  - Beta2-microglobulin (beta2-MG) is a pharmacodynamic marker of interferon-beta
      activity in multiple sclerosis (MS). Its role in the natural course of the
      disease is not fully known. We analyzed the spontaneous fluctuation of beta2-MG
      in free-treatment MS patients during a short-time course to quantify beta2-MG as
      a marker of disease activity/progression. Thirty MS patients were clinically
      assessed and imaged monthly over a 3-month period. Sera were collected
      concomitantly for the evaluation of beta2-MG, by means of an enzyme-linked
      immunosorbent assay. Sera from 20 healthy individuals (HI) were drawn and used as
      controls. The Mann-Whitney test was used when appropriate and time effect on
      radiological and biological measures was assessed by means of the random effect
      models. Eight (26.7%) patients experienced a clinical relapse but three (10%)
      required steroid treatment. A reduction in the contrast-enhancing lesion load (P
      = 0.02) and a trend (P = 0.07) toward a decrease in brain parenchyma fraction
      were observed. Baseline levels of beta2-MG were similar in patients and HI.
      Patients' beta2-MG values increased over the 3-month time period (P = 0.05) but
      did not exceed those detected in HI at any time point. These results failed to
      demonstrate the validity of beta2-MG as a surrogate marker of disease in MS.

PMID- 15257684
TI  - Prevalence of persistent vegetative state/apallic syndrome in Vienna.
AB  - The aim of the project was to survey the hospital prevalence of apallic syndrome
      in a federal state in Austria at an exact point in time. To achieve this, a point
      prevalence study was carried out on 28 November 2001 in the Vienna region. The
      central element was a questionnaire, which provided an exact recording of the
      patients' condition. An additional preliminary task was to check all the
      discharge diagnoses in the hospitals of the Vienna Hospital Association (Wiener
      Krankenanstalten Verbund) between 1996 and 2000 according to the ICD-9 diagnoses
      for apallic syndrome. These data should serve to cross-check the recorded
      results. All hospitals (n = 48) and nursing facilities (n = 44) in Vienna were
      included in this investigation. As the aim of the study was to record the
      prevalence of apallic syndrome in the population of Vienna, four patients of the
      group with full-stage apallic syndrome (n = 36) were excluded as they were from
      other federal states. In total, 32 hospital patients who met the clinical
      criteria for apallic syndrome (full-stage) were recorded. The point prevalence of
      apallic syndrome was 1.9/100,000 inhabitants. As a result of this study, the
      exact survey of hospital prevalence of apallic syndrome could be found. As a
      consequence, the Viennese government has developed a rehabilitation concept for
      patients with apallic syndrome in Vienna.

PMID- 15257685
TI  - A new approach in anti-epileptic drug evaluation.
AB  - Presurgical trials with video-electroencephalogram (EEG) monitoring for a couple
      of days provide the possibility to objectively and quantitatively analyze seizure
      activity during different drug treatments. Patients are provided with the optimal
      medical care and safety precautions when hospitalized. Hereby a method used in
      the antiepileptic drug (AED) trials called therapeutic intensive seizure analysis
      (TISA) has been recently introduced, by which AED efficacy on seizure activity
      can be objectively quantified by using continuous video-EEG monitoring. This
      could be used not only as a supplement to the traditional evaluation of AEDs'
      efficacy by treatment failure designs in large groups, but also can provide early
      individual information on the changes of seizure activity of each patient during
      the therapy. Data from TISA studies suggest that secondarily generalized tonic
      clonic seizures (SGTCs) mostly occur in patients with a SGTC history after
      withdrawal of AED. The first 3 days of titration of a newly introduced AED was
      important for efficacy assessment; with a low risk of SGTCs. By using the TISA
      method an early recognition of first effects of a new AED on seizure activity and
      neuropsychological changes is possible, which can be correlated to serum
      concentration levels in a small sample size. The essentials of the proposed
      modification to the conventional presurgical trial are: (1) a complete withdrawal
      of AEDs should be avoided, if possible and (2) a titration phase limited to 3
      days is suggested, using a condensed evaluation setting including the TISA
      method, serum concentration and neuropsychological monitoring. In addition long
      term effects can be evaluated by repeated video-EEG monitoring.

PMID- 15257686
TI  - High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open
      study in a tertiary care centre.
AB  - The aim of this study was to investigate the efficacy of riboflavin for the
      prevention of migraine. An open label study was performed in a specialized
      outpatient clinic. Patients received 400 mg riboflavin capsules per day. Headache
      frequency, duration, intensity and the use of abortive drugs were recorded at
      baseline and 3 and 6 months after treatment. Headache frequency was significantly
      reduced from 4 days/month at baseline to 2 days/month after 3 and 6 months (P <
      0.05). The use of abortive drugs decreased from 7 units/month to 4.5 units/month
      after 3 and 6 months of treatment (P < 0.05). In contrast, headache hours and
      headache intensity did not change significantly. We could demonstrate a
      significant reduction of headache frequency following riboflavin treatment. In
      addition, the number of abortive anti-migraine tablets was reduced. In line with
      previous studies our findings show that riboflavin is a safe and well-tolerated
      alternative in migraine prophylaxis.

PMID- 15257687
TI  - Pain and sensory complaints in multiple sclerosis.
AB  - Pain is a frequent and disabling symptom among multiple sclerosis (MS) patients.
      The importance of this problem was investigated in a hospital based MS
      population. A total of 142 MS patients underwent neurological examination and a
      structured interview for registration of pain and sensory symptoms. One-hundred
      and five patients reported sensory and/or pain symptoms. Pain was reported by 93
      patients and was most frequently located in the limbs and lumbar region. The
      presence of pain was independent of gender, age at onset and examination,
      disability, disease course and duration. The most frequently reported
      characteristics of the symptoms were paresthesia, neuralgia and deep muscular
      aching. About 40% of the patients reported that the symptoms had important
      influence on daily activities. Only one-third of the patients were treated for
      their pain. Pain is a frequent and disabling symptom, independent of demographic
      and clinical variables in MS patients. The low frequency of treatment for these
      symptoms indicates a need for improved attention to this problem.

PMID- 15257688
TI  - Pergolide mesylate can improve sexual dysfunction in patients with Parkinson's
      disease: the results of an open, prospective, 6-month follow-up.
AB  - One of the most disabling problems in males suffering from advanced Parkinson's
      disease (PD) is complex sexual dysfunction. The effect of dopamine replacement or
      dopaminergic stimulation on sexual dysfunction has been recently examined and
      described in patients treated by L-DOPA or apomorphine. Pergolide mesylate is
      another dopamine agonist with a known high affinity to hD(2S) subtype and a lower
      affinity to hD(2L) subtype of D2 dopaminergic receptors. It has been repeatedly
      shown to be a highly effective treatment of the complicated and advanced stages
      of PD. The current study has been designed to assess its efficacy in the
      treatment of sexual dysfunction, which frequently accompanies the complicated
      stage of PD in males. Fourteen male patients suffering from PD, each of whom had
      been treated with L-DOPA, and in whom additional treatment with peroral
      dopaminergic agonist (DA) was needed, were followed for a 6-month period.
      Pergolide mesylate (Permax) was given to each patient, and titrated to a total
      daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments
      performed before the start of pergolide treatment consisted of a neurological
      examination, including Unified Parkinson's Disease Rating Scale (UPDRS) III and
      IV subscales scoring, Mini Mental State Examination (MMSE) scoring, the
      neuropsychological examination including Zung scale scoring to exclude
      depression, biochemical and haematological examinations including the examination
      of prolactine serum levels; and a sexological examination during which the
      patients filled-in the International Index of Erectile Function (IIEF)
      questionnaire. These examinations were repeated during the control assessments at
      months 1, 3 and 6. To compare the examination results, anova, Friedmann's anova
      (non-parametric) and Tukey post hoc tests were used. There were statistically
      significant differences between the values of UPDRS III motor subscale, UPDRS IV
      (complications of therapy) subscale and all subscales of IIEF when months 0 and 1
      were compared with the results obtained at months 3 and 6. The differences
      between months 0 and 1 and months 3 and 6 (in these items) were virtually
      insignificant. In conclusion, pergolide substantially improved sexual function in
      the younger male patients who were still interested in sexual activities. In such
      cases, the introduction of pergolide might be a better choice than treatment with
      sildenafile, which usually meets several contraindications in common PD male
      population.

PMID- 15257689
TI  - Type I cerebral dural arteriovenous fistulas of the lateral sinus: clinical
      features in 24 patients.
AB  - To review the clinical and diagnostic characteristics of type I cerebral dural
      arteriovenous fistulas (CDAVF) of the lateral sinus medical records of 24
      patients with Type I CDAVF were retrospectively reviewed. All patients were
      interviewed aiming at presenting symptoms, impact on daily functioning,
      diagnostic delay, relevant medical history and post-treatment status. Nineteen of
      24 patients (79%) were women. The median age at the time of diagnosis was 56
      years (range 32-69). Unilateral pulsatile tinnitus was the presenting symptom in
      all patients. A bruit could be heard at auscultation on the retroauricular skull
      in all patients. The median diagnostic delay was 17.9 months (range 1-120).
      Standardized magnetic resonance imaging (MRI) of the brain was normal in all
      patients. The diagnosis of CDAVF was confirmed on cerebral angiography. In
      conclusion, CDAVF type I of the lateral sinus occurs predominantly in middle aged
      women and presents with unilateral pulsatile tinnitus, which resulted in
      impairment of social and occupational functioning in the vast majority of
      patients. An audible bruit at retroauricular auscultation confirms the clinical
      diagnosis of a cerebral dural fistula. MRI is not helpful in the diagnosis and
      cerebral angiography is indicated to classify the dural fistula.

PMID- 15257690
TI  - Trousseau's syndrome related to adenocarcinoma of the colon and
      cholangiocarcinoma.
AB  - Malignancy-related thromboembolism, so-called Trousseau's syndrome, can present
      as acute cerebral infarction, non-bacterial thrombotic endocarditis (NBTE) and
      migratory thrombophlebitis. It is usually attributed to a cancer-related
      hypercoagulable state, chronic disseminated intravascular coagulopathy (DIC), or
      tumour embolism. We report on two patients with adenocarcinoma of the colon and
      cholangiocarcinoma who developed widespread thromboembolism during disease
      progression. Both did poorly despite aggressive institution of anticoagulation
      therapy. These cases emphasize that cerebral infarction or refractory
      thromboembolism in cancer-treated patients should prompt investigation for
      recurrent or metastatic disease or progression of the underlying malignancy.
      Optimal treatment remains to be established.

PMID- 15257691
TI  - Acute weakness in a previously asymptomatic elderly lady.

PMID- 15257692
TI  - MRI of acute brainstem ischaemia: cytotoxic versus vasogenic oedema?

PMID- 15257698
TI  - Spontaneous lesser sac haematoma in a haemophiliac.

PMID- 15257699
TI  - Calcineurin-inhibitor pain syndrome following haematopoietic stem cell
      transplantation.

PMID- 15257700
TI  - Advances in the molecular and serological diagnosis of invasive fungal infection
      in haemato-oncology patients.
AB  - Current laboratory diagnostic methods for invasive fungal infection (IFI) in
      haemato-oncology patients are insensitive, resulting in late diagnosis and
      contributing to high mortality. In recent years, progress has been made in the
      development and evaluation of sensitive sero-diagnostic assays, including
      detection of genomic DNA sequences and fungal antigens, which aid in a rapid,
      early diagnosis of IFI. The sensitivity and specificity of the assays vary
      considerably between studies, highlighting the need to correlate serological
      results with conventional laboratory tests and clinical or radiological findings.
      As part of management protocols, these assays may help to confirm the diagnosis
      of suspected IFI; however, the impact on mortality from IFI may be greatest when
      they are used to screen high-risk patients. Persistently positive screening
      results could direct early aggressive antifungal therapy, guided further by
      radiological and microbiological findings combined with regular clinical review,
      while the excellent negative predictive value may allow treatment to be withheld
      in patients with antibiotic resistant neutropenic fever but no other signs of
      IFI. However, this pre-emptive approach requires evaluation in prospective
      randomized trials.

PMID- 15257701
TI  - P-selectin in haemostasis.
AB  - During the past decade, interrelationships between inflammation and thrombosis
      have been the subject of extensive works, and it is now commonly recognized that
      inflammation (notably leucocyte recruitment) directly affects thrombosis, and
      that thrombosis also constitutes a pro-inflammatory event. This tight link is
      partly attributable to P-selectin, which is functional not only when expressed on
      the surface of activated platelets and endothelial cells, but also when shed,
      generating its soluble form, termed sP-selectin. In this review, we will provide
      an overview of the relative roles of the different compartments of P-selectin
      (platelet, endothelial cell, plasma) in haemostasis and vascular pathologies, and
      the potential therapeutic benefits achievable in targeting this molecule.

PMID- 15257702
TI  - Complex chromosomal abnormalities in utero, 5 years before leukaemia.
AB  - Prenatal acquisition of leukaemia-associated gene rearrangements is a well
      established phenomenon. This is the first report of a complex cytogenetic clone,
      in association with an ETV6/AML1 fusion, developing in utero. Identical twin
      girls, aged 4 years, developed ETV6/AML1-positive acute lymphoblastic leukaemia
      (ALL) within 3 months of one another. Both demonstrated an identical four way,
      variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6
      one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1
      fusion and the associated complex chromosomal rearrangements occurred in utero.
      Clonal expansion of the abnormal cell in one twin was followed by metastasis to
      the other. There was a prolonged preleukaemic phase, which lasted well into
      childhood. The short time between the two diagnoses of ALL suggests a common
      precipitating event. The significance of the different secondary markers remains
      unclear.

PMID- 15257703
TI  - Aberrant expression of beta-catenin discriminates acute myeloid leukaemia from
      acute lymphoblastic leukaemia.
AB  - The role of beta-catenin in epithelial neoplasms has been widely studied whereas
      current knowledge regarding beta-catenin gene and protein expression in bone
      marrow cells derived from normal haematopoiesis and clonal haematological
      disorders is lacking. beta-Catenin gene expression was quantitatively
      investigated in bone marrow cells derived from clonal haematological disorders
      [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia
      chromosome-positive chronic myeloid leukaemia (Ph+ CML], Ph- myeloproliferative
      disorders, n = 96) compared with non-neoplastic haematopoiesis (n = 33) by real
      time reverse transcription polymerase chain reaction. Cellular localization of
      beta-catenin protein was detected by immunocytochemistry. beta-Catenin gene
      expression was significantly increased in AML compared with ALL cases (P <
      0.0001), Ph+ CML (P < 0.0001) and non-neoplastic haematopoiesis (P = 0.019).
      Immunocytochemistry revealed that, in non-neoplastic haematopoiesis, the
      granulopoietic lineage as well as megakaryocytes showed membranous and
      cytoplasmic staining to various degrees along with unlabelled nuclei. Besides
      haematopoiesis, beta-catenin prominently marked bone marrow vascularity and
      diverse stroma cells. beta-Catenin gene was inversely expressed in AML and ALL
      with a lack of protein expression in neoplastic cells in ALL. In contrast, the
      other haematological disorders under study, except for Ph+ CML, did not show
      significant alterations of overall beta-catenin gene expression compared with
      normal bone marrow. These data suggest different regulatory mechanisms in the
      expression and function of beta-catenin in haematopoietic cells.

PMID- 15257704
TI  - Classical and molecular cytogenetic abnormalities and outcome of childhood acute
      myeloid leukaemia: report from a referral centre in Israel.
AB  - The incidence of cytogenetic abnormalities in childhood de novo acute myeloid
      leukaemia (AML) and its prognostic significance was assessed in an Israeli
      paediatric referral centre. Cytogenetic analysis was successful in 86 of 97
      children (< 20 years of age) diagnosed between 1988 and 2002 with de novo AML.
      Fluorescence in situ hybridization analysis detected new information in 11 of
      them, leading to reassignment in cytogenetic group classification. The incidence
      of the various cytogenetic subgroups was as follows: normal - 9%; t(11q23) - 22%;
      t(8;21) - 13%; t(15;17) - 8%; inv(16) - 3.4%; abn(3q) - 4.6%; 7/7q-(sole or main)
      - 5.8%; del(9q)(sole) and +21(sole) - 4.6% each; t(8;16) - 2.3%; t(6;9), t(1;22),
      +8(sole) - 1.1% each; and miscellaneous - 18%. The overall survival (OS) and
      event-free survival (EFS) (4 years) for 94 patients treated with the modified
      Berlin-Frankfurt-Munster (BFM) AML protocols (non-irradiated) were 59.9% (SE =
      5%) and 55.7% (SE = 5%), respectively, and for the favourable t(8;21), t(15;17)
      and inv(16), OS was 60% (SE = 15%), 83% (SE = 15%) and 100% respectively. For the
      normal group it was 62% (SE = 17%), miscellaneous 64% (SE = 12%), t(11q23) 44.6%
      (SE = 11%) and of the -7/7q-, del(9q)(sole) or t(6;9), none had survived at 4
      years. The incidence of cytogenetic subgroups in the Israeli childhood AML
      population and their outcome were similar to other recently reported paediatric
      series. Cytogenetic abnormalities still carry clinical relevance for treatment
      stratification in the context of modern chemotherapy.

PMID- 15257705
TI  - Functional analysis of apoptosis induction in acute myeloid leukaemia-relevance
      of karyotype and clinical treatment response.
AB  - Deficiencies or structural defects of the apoptotic machinery have been
      postulated as a potential mechanism for a broad resistance of acute myeloid
      leukaemia (AML) blasts towards cytotoxic therapy comprising chemotherapeutic
      agents with diverse pharmacodynamic principles but also cell-mediated
      cytotoxicity of the graft-versus-leukaemia effect, for example, in the setting of
      allogeneic transplantation. This hypothesis was systematically tested by
      functionally analysing the early, intermediate and late events of the apoptotic
      process in primary AML (n = 31) blasts following activation of the intrinsic and
      extrinsic pathway of apoptosis (etoposide and cytarabine as DNA damaging agents,
      FAS-ligand as an activator of the death receptor pathway). Activation of the
      extrinsic pathway by FAS-ligand did not induce apoptosis in primary AML, instead
      the proapoptotic signal was shown to 'fade', even in the early phase of the
      apoptotic sequence. However, activation of the intrinsic pathway induced severe
      cytotoxicity in all samples that showed the characteristic features of typical
      apoptosis, with a prominent apoptotic volume decrease (blebbing) in the early
      phase, significant increases in caspase 3 activity (intermediate or effector
      phase) and breakdown of cellular energy production in the late phase of
      apoptosis. These characteristics did not differ between prognostically favourable
      versus unfavourable AML karyotypes or between clinically responding versus
      refractory AML--indicating that a functional apoptotic apparatus is present even
      in the unfavourable AML subgroups. Our data indicate that the mechanism for a
      broad clinical resistance is not a dysfunctional apparatus per se but rather the
      consequence of anti-apoptotic regulation impeding otherwise functional apoptotic
      machinery.

PMID- 15257706
TI  - Serum free light chains for monitoring multiple myeloma.
AB  - Monoclonal immunoglobulin free light chains (FLC) are found in the serum and
      urine of patients with a number of B-cell proliferative disorders, including
      multiple myeloma. Automated immunoassays, which can measure FLC in serum, are
      useful for the diagnosis and monitoring of light chain (AL) amyloidosis, Bence
      Jones myeloma and non-secretory myeloma patients. We report the results of a
      study investigating the utility of serum FLC measurements in myeloma patients
      producing monoclonal intact immunoglobulin proteins. FLC concentrations were
      measured in presentation sera from 493 multiple myeloma patients with monoclonal,
      intact immunoglobulin proteins. Serial samples were assayed from 17 of these
      patients and the FLC measurements were compared with other disease markers. Serum
      FLC concentrations were abnormal in 96% of patients at presentation. FLC
      concentrations fell more rapidly in response to treatment than intact
      immunoglobulin G (IgG) and showed greater concordance with serum beta2
      microglobulin concentrations and bone marrow plasma cell assessments. It was
      concluded that serum FLC assays could be used to follow the disease course in
      nearly all multiple myeloma patients. In addition, because of their short serum
      half-life, changes in serum FLC concentrations provide a rapid indication of the
      response to treatment.

PMID- 15257707
TI  - The recurrent translocation t(14;20)(q32;q12) in multiple myeloma results in
      aberrant expression of MAFB: a molecular and genetic analysis of the chromosomal
      breakpoint.
AB  - Chromosomal translocations of the immunoglobulin heavy chain (IgH) gene region at
      14q32 are regularly involved in B lymphoid malignancies; they may initiate
      transformation either by deregulation of existing (proto) oncogenes or creation
      of new hybrid genes with transforming properties. Previously, we reported a
      reciprocal novel translocation, t(14;20)(q32;q12), found in the myeloma cell line
      UM3. In this cell line, the t(14;20) is the only translocation involving the IgH
      locus. Using double colour immunofluorescence in situ hybridization, the t(14;20)
      was also found in the diagnostic bone marrow sample, excluding a possible in
      vitro artefact. We also have found this recurrent t(14;20) in four other cell
      lines and in additional patient material. We cloned the regions containing the
      breakpoints in the der(14) and der(20) chromosomes from UM3, and analysed ectopic
      mRNA expression of genes in the breakpoint regions of both derivative
      chromosomes. Ectopic gene expression was observed for the transcription factor
      MAFB in der(14). The breakpoint scatter in the five cell lines with a t(14;20)-
      all expressing MAFB--is comprised within a region of 0.8 Mb. Provisional data
      indicate that this t(14;20) is associated with an adverse prognosis. Aberrant
      expression of MAFB may be involved in the oncogenic transformation of myeloma
      cells that harbour the t(14;20).

PMID- 15257708
TI  - Bone marrow histological patterns can predict survival of patients with grade 1
      or 2 follicular lymphoma: a study from the Groupe d'Etude des Lymphomes
      Folliculaires.
AB  - The influence of bone marrow biopsy (BMB) histology on prognosis and management
      of follicular lymphomas (FL) remains controversial. A total of 390 patients with
      grade 1 or 2 FL were prospectively included in the multicentric Groupe d'Etude
      des Lymphomes Folliculaires trial and their BMB reviewed in order (i) to quantify
      the ratio of lymphomatous foci (LFo) area to that of BMB size (LFo/BMB), (ii) to
      determine the BMB patterns for a practical grading of marrow infiltration, (iii)
      to assess the intra- and inter-observer reproducibility of this grading and (iv)
      to analyse this grading on event-free (EFS) and overall survival (OS), using
      univariate and multivariate analyses. A total of 267 patients (68%) had BMB
      involvement, with inter- and intra-observer reproducibility for classifying the
      patterns of involvement of 91 and 96%, respectively. Uni- and multivariate
      analyses demonstrated the adverse influence of (i) a ratio of LFo/BMB > or = 0.1,
      i.e. three or four nodules/medullary space or > or = 1 nodule + foci of diffuse
      involvement on EFS (P = 0.03) and (ii) two different histological patterns in the
      same BMB on EFS (P = 0.004) and OS (P = 0.001). This latter finding was only
      significant in patients with a high tumour burden and remained significant in
      multivariate analysis. These results indicate that BMB histology can predict
      survival of FL patients with a high tumour burden, and may help in defining their
      treatment.

PMID- 15257709
TI  - Prospective evaluation of procalcitonin in adults with febrile neutropenia after
      haematopoietic stem cell transplantation.
AB  - Serum procalcitonin (PCT) levels have been proposed as a new discriminative
      marker for bacterial and fungal infections. We analysed the diagnostic relevance
      of PCT in febrile episodes of neutropenic adult patients after haematopoietic
      stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile
      episodes, classified according to the final diagnosis as: neutropenic fever of
      unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented
      infection and non-infectious febrile episodes (n = 10). On first day of fever,
      mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown
      origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml
      (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever
      (P = not significant). Five days after the antibiotic therapy was started, fever
      persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed
      with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml
      (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis
      indicates that the PCT level on first day of fever did not facilitate the
      differential diagnosis of neutropenic febrile episode. However, when fever
      persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and
      specificity for the diagnosis of invasive aspergillosis.

PMID- 15257711
TI  - Resonance-thrombography indices of the haemostatic process in relation to risk of
      incident coronary heart disease: 9 years follow-up in the Caerphilly Prospective
      Heart Disease Study.
AB  - Global assays, such as resonance-thrombography (RTG), which measure the
      interaction between platelets, coagulation and fibrinolysis have been used as
      summary measures of risk for over two decades but have not been evaluated in
      epidemiological studies. We examined whether RTG indices are risk indicators for
      incident coronary heart disease (CHD). RTG indices, related haematological
      variables and other risk factors were measured between 1984 and 1988 in a cohort
      of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were
      associated with lifestyle risk factors. During 9 years of follow-up, 282 (12%)
      men developed a major new CHD event, as classified by World Health Organization
      criteria. On adjustment for age, only r and AF measured at baseline were related
      to risk of incident CHD. On multivariate adjustment in a multiple logistic
      regression model that included age, diastolic blood pressure, body mass index,
      total and high-density lipoprotein cholesterol, lifestyle risk factors and use of
      prescribed medicine, these associations weakened but remained significant.
      Additional adjustment for fibrinogen, viscosity, white cell count and fibrin d
      dimer either reduced these associations to non-significance (AF) or to borderline
      significance (r).

PMID- 15257710
TI  - Haploidentical donor T cells fail to facilitate engraftment but lessen the immune
      response of host T cells in murine fetal transplantation.
AB  - The effects of donor T cells, or their CD8+ subset, on engraftment and tolerance
      induction in fetal transplantation were evaluated using an F1-into-parent mouse
      model that does not permit a graft-versus-host effect. Gestational day 13 C57BL/6
      (H-2Kb) fetuses were transplanted with B6D2F1 (H-2Kb/d) light density bone marrow
      cells (LDBMC) containing 1-2% T cells, T-cell depleted bone marrow cells (TDBMC,
      < 0.1% T cells), or TDBMC with enriched CD8+ T cells (CD8). Chimaerism levels in
      the peripheral blood, spleen and bone marrow were usually below 0.2% in all
      groups, indicating that T cells do not improve engraftment without a graft-versus
      host effect. A significant, but transient, wave of donor cells was seen in the
      peripheral blood at 1 month of age in the CD8 and LDBMC groups. Relatively high
      levels of chimaerism (< 17%) were sometimes detected in the peritoneal cavities
      of recipients. T-cell tolerance specific to donor cells was evaluated in mixed
      lymphocyte cultures. The CD8 and LDBMC groups had significantly lower T-cell
      responses than untransplanted controls. These findings indicate that in utero
      transplantation of haploidentical donor CD8+ or CD3+ cells can help to lessen the
      immune response of host T cells towards donor cells. The persistence of donor
      cells in the peritoneal cavity also correlated with tolerance induction.

PMID- 15257712
TI  - Phenotypic sensitivity to activated protein C in healthy families: importance of
      genetic components and environmental factors.
AB  - The relative importance of environmental factors and genetic components other
      than factor V Leiden on the sensitivity to activated protein C (APC) in healthy
      nuclear families was determined. We studied 149 European families (298 parents
      and 278 biological offspring aged more than 6 years). APC response was measured
      and expressed as normalized APC-sensitivity ratio (n-APC-SR). Subjects were
      genotyped for G1691A and G20210A polymorphisms of factor V and II genes; levels
      of factors II, V and VIII, antithrombin, cholesterol, high-density lipoprotein
      cholesterol and triglycerides were measured. After identifying variables
      influencing the n-APC-SR by a stepwise multiple regression model, variance
      component analysis was used. The heritability (proportion of the overall
      variability of a trait due to polygenic effects) of n-APC-SR was determined after
      adjustment for all clinical and laboratory variables, including factor V Leiden.
      Heritability coefficients (mean +/- standard deviation) were different for males
      (0.68 +/- 0.06) and females (0.34 +/- 0.12) younger than 25 years and in subjects
      older than 25 years: 0.37 +/- 0.09. This analysis provides strong evidence for a
      polygenic component influencing n-APC-SR in addition to factor V Leiden and
      suggests age- and gender-specific genetic effects.

PMID- 15257713
TI  - Efficacy and inhibitor development in previously treated patients with
      haemophilia A switched to a B domain-deleted recombinant factor VIII.
AB  - There have been recent reports of unexpected poor efficacy of a B-domain-deleted
      recombinant factor VIII (BDD-rFVIII) in haemophiliacs, and inhibitor development
      in previously treated patients (PTPs) switched to BDD-rFVIII. The results of a 6
      month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all
      switched to BDD-rFVIII, were used to evaluate efficacy and inhibitor development.
      The prospective study showed that 89% of 362 bleeds were controlled by one to two
      infusions, reproducing the efficacy profiles of other recombinant products
      (rFVIIIs). One patient, previously treated with plasma-derived FVIII only,
      developed a high titre inhibitor (30 BU) after 5 days of exposure. The
      retrospective survey, carried out in the total Italian PTP population switched to
      BDD-rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of
      < or = 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of >
      50 days. One patient developed an inhibitor: he was a high-risk, severe PTP
      previously exposed to another rFVIII for 3 days only. Among the entire low-risk
      population of severe Italian PTPs switched to BDD-rFVIII (25 in the prospective
      study, 49 in the retrospective cohort) only one developed an inhibitor (1.3%).
      These data indirectly support the views that BDD-rFVIII is equivalent to other
      rFVIIIs in term of efficacy and inhibitor development.

PMID- 15257714
TI  - Intraindividual consistency of the activated protein C resistance phenotype.
AB  - Resistance to activated protein C (APC) has been demonstrated to be a risk factor
      for venous thromboembolism, but it is not known whether this phenotype is
      consistent over time. We reinvestigated 2580 subjects from the Vicenza
      Thrombophilia and Atherosclerosis (VITA) Project to evaluate the prevalence of a
      consistent APC resistance phenotype in the population. Among the 433 subjects
      with an APC resistance at first visit, the phenotype was confirmed in all the 74
      factor V (FV) Leiden carriers and in 124 of 359 FV Leiden negative subjects
      (34%). The prevalence of a confirmed phenotype, not associated with FV Leiden,
      was 4.8% in our population. In a subgroup of subjects previously investigated for
      heritability of the APC resistance, we confirmed the APC resistance phenotype in
      seven of 39 (17.9%) subjects with an APC resistant sibling but only in 20 of 408
      (4.9%) subjects without a sibling with the same phenotype (P = 0.005). Among the
      124 FV Leiden negative subjects with a persistent APC resistance phenotype, 40
      (32%) had a plasma factor VIII coagulant activity level above 150 IU/dl and eight
      (6.4%) were carriers of the G20210A prothrombin allele. APC resistance not due to
      FV Leiden is a frequent and consistent phenotype in the general population, with
      a possibly strong genetic influence.

PMID- 15257715
TI  - Human cytomegalovirus persists in myeloid progenitors and is passed to the
      myeloid progeny in a latent form.
AB  - CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however,
      the mechanisms of HCMV latency remain unclear. We have investigated the effects
      of the haematopoietic lineage restriction on the establishment and spread of the
      latent HCMV to progeny cells. In vitro-infected and latently-infected
      haematopoietic progenitor cells derived from HCMV seropositive donors were
      studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was
      determined by single colony polymerase chain reaction and fluorescent in situ
      hybridization (FISH). The presence of CMV DNA was found to be restricted to
      myeloid progenitors and the percentage of HCMV-infected cells was lower in
      naturally-infected cells than in in vitro-infected cells. Erythroid
      differentiation resulted in an abortive infection with persistence of the viral
      nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors,
      HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of
      granulocyte-macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for
      extended periods of time. No viral production could be detected throughout the
      culture but the comparison of the numbers of latently-infected cells prior to and
      after the culture suggests that proliferation of haematopoietic progenitor cells
      may lead to the expansion of latently-infected cells.

PMID- 15257716
TI  - Disturbed flow promotes deposition of leucocytes from flowing whole blood in a
      model of a damaged vessel wall.
AB  - Departure from simple laminar flow in arteries may promote the local attachment
      of leucocytes either to intact endothelium or platelet thrombi. We perfused blood
      through a chamber with a backward facing step, to observe whether adhesion from
      whole blood to P-selectin was indeed localized to a region of recirculating flow,
      and whether platelets binding to collagen in such a region could capture
      leucocytes. Blood flowing over the step established a stable vortex, a
      reattachment point where forward and backward flow separated, and a simple
      laminar flow with wall shear rate c. 400/s further downstream. Fluorescently
      labelled leucocytes were observed to attach to P-selectin immediately upstream or
      downstream of the reattachment point, and to roll back towards the step or away
      from it, respectively. There was negligible adhesion further downstream. When a P
      selectin-Fc chimaera was used to coat the chamber, stable attachment occurred,
      again preferentially in the disturbed flow region. Numerous platelets adhered to
      a collagen coating throughout the chamber, although there were local maxima
      either side of the reattachment point. The adherent platelets captured flowing
      leucocytes in these regions alone. Leucocytes may adhere from flowing blood in
      vessels with high shear rate if the flow is disturbed. While platelets can adhere
      over a wider range of shear rates, their ability to capture leucocytes may be
      restricted to regions of disturbed flow.

PMID- 15257717
TI  - Evidence of parvovirus B19 infection in patients of pre-eclampsia and eclampsia
      with dyserythropoietic anaemia.
AB  - Parvovirus B19 (PVB19) infection can induce transient anaemia in patients with
      increased erythropoiesis. However, the dynamic change within the bone marrow
      after PVB19 infection is not well understood. Increased erythropoiesis is a
      physiological phenomenon in puerperital women. Nevertheless, anaemia as a result
      of PVB19 infection in puerperital women has never been reported. We report one
      patient with eclampsia and two patients with pre-eclampsia who had transient,
      severe anaemia during the puerperital period because of PVB19 infection. Viral
      genomes were detected in the peripheral blood during the anaemic period by
      polymerase chain reaction and became undetectable after the anaemia was resolved.
      Viral genomes and protein could also be detected in bone marrow by in situ
      hybridization and immunohistochemical staining, respectively. Serial aspiration
      cytology of bone marrow showed severe dysplastic change involving erythroid
      precursors with a few apoptotic cells at the initial onset of anaemia, markedly
      increased apoptotic cells that was confirmed by the increased expression of
      activated caspase 3, around the nadir of anaemia, and a normal marrow picture
      without features of apoptosis after recovery from anaemia. Our data indicates
      that PVB19 infection can induce transient, severe dyserythropoietic anaemia in
      puerperital women with pre-eclampsia/eclampsia and the pathogenetic mechanism may
      probably involve the induction of apoptosis following PVB19 infection.

PMID- 15257718
TI  - Increased hepcidin expression and hypoferraemia associated with an acute phase
      response are not affected by inactivation of HFE.
AB  - The effect of HFE inactivation on iron homeostasis during an acute phase response
      was investigated in mice. HFE knockout, beta2-microglobulin knockout and C57BL/6J
      mice were injected with Freund's Complete Adjuvant to induce an acute phase
      response and hepatic hepcidin expression and serum transferrin saturation was
      determined 16 h later. Hepcidin mRNA increased in all strains in response to an
      acute phase stimulus when compared with untreated control animals. Hypoferraemia
      also occurred in all strains, indicating that both the upregulation of hepcidin
      and the decrease in transferrin saturation associated with an acute phase
      response is not dependent on HFE function.

PMID- 15257719
TI  - Identification of a novel IGH-MMSET fusion transcript in a human myeloma cell
      line with the t(4;14)(p16.3;q32) chromosomal translocation.

PMID- 15257721
TI  - Is the placebo powerless? Update of a systematic review with 52 new randomized
      trials comparing placebo with no treatment.
AB  - BACKGROUND: It is widely believed that placebo interventions induce powerful
      effects. We could not confirm this in a systematic review of 114 randomized
      trials that compared placebo-treated with untreated patients. AIM: To study
      whether a new sample of trials would reproduce our earlier findings, and to
      update the review. METHODS: Systematic review of trials that were published since
      our last search (or not previously identified), and of all available trials.
      RESULTS: Data was available in 42 out of 52 new trials (3212 patients). The
      results were similar to our previous findings. The updated review summarizes data
      from 156 trials (11 737 patients). We found no statistically significant pooled
      effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence
      interval 0.89-1.01). The effect on continuous outcomes decreased with increasing
      sample size, and there was considerable variation in effect also between large
      trials; the effect estimates should therefore be interpreted cautiously. If this
      bias is disregarded, the pooled standardized mean difference in 118 trials with
      continuous outcomes was -0.24 (-0.31 to -0.17). For trials with patient-reported
      outcomes the effect was -0.30 (-0.38 to -0.21), but only -0.10 (-0.20 to 0.01)
      for trials with observer-reported outcomes. Of 10 clinical conditions
      investigated in three trials or more, placebo had a statistically significant
      pooled effect only on pain or phobia on continuous scales. CONCLUSION: We found
      no evidence of a generally large effect of placebo interventions. A possible
      small effect on patient-reported continuous outcomes, especially pain, could not
      be clearly distinguished from bias.

PMID- 15257722
TI  - Influence of smoking and snus on the prevalence and incidence of type 2 diabetes
      amongst men: the northern Sweden MONICA study.
AB  - OBJECTIVE: To explore the effect of smoking and smokeless tobacco, 'snus', on the
      risk of type 2 diabetes. DESIGN: Population-based cross-sectional and prospective
      follow-up study in northern Sweden. SUBJECTS: A total of 3384 men, aged 25-74
      years, who participated in the MONICA study in 1986, 1990, 1994 or 1999, 1170 of
      whom had an oral glucose tolerance test. In 1999, 1757 men from previous cohorts
      returned for re-examination. Main outcome measures. We compared the prevalence of
      type 2 diabetes or pathological glucose tolerance (PGT) amongst tobacco users to
      that of nonusers at entry into the study and at follow-up, using odds ratios.
      RESULTS: Compared with never users, the age-adjusted risk of prevalent clinically
      diagnosed diabetes for ever smokers was 1.88 (CI 1.17-3.0) and for smokers 1.74
      (0.94-3.2). Corresponding odds ratios for snus users were 1.34 (0.65-2.7) and
      1.18 (0.48-2.9). We found no increased risk of prevalent PGT in snus users or
      smokers. Former smokers and snus users had an insignificantly increased risk for
      PGT. Compared with nonusers, the age-adjusted risk of developing clinically
      diagnosed diabetes during follow-up was 4.63 (1.37-16) in consistent exclusive
      smokers, 3.20 (1.16-8.8) in ex-smokers and no cases in consistent snus users. The
      risk of PGT during follow-up was not increased in consistent tobacco users but
      evident, although not statistically significant, in those who quit snus during
      the follow-up period, 1.85 (0.60-5.7). Adjustment for physical activity and
      alcohol consumption did not change the major findings. CONCLUSIONS: The risk of
      diabetes for snus users was not significantly increased. Smoking was associated
      with prevalent and incident cases of diabetes. Ex-tobacco users tended towards
      more PGT.

PMID- 15257723
TI  - Tobacco and myocardial infarction in middle-aged women: a study of factors
      modifying the risk.
AB  - BACKGROUND: Although myocardial infarction (MI) is strongly related to smoking,
      few have studied why some smokers are more vulnerable than others. This study
      explored how the risk of MI in current and former smokers is modified by other
      cardiovascular risk factors. METHODS: Incidence of MI (fatal and nonfatal)
      amongst 10619 women, 48.3 +/- 8.2 years old, were studied in relation to smoking,
      hypertension, hypercholesterolaemia, diabetes, marital status and occupational
      level over a mean follow-up of 14 years. RESULTS: Of the 3738 smokers, one-third
      had at least one major biological risk factor besides smoking; 228 women had MI
      during follow-up. Smoking and hypertension showed a synergistic effect on
      incidence of MI. The adjusted relative risks (RR) were 12.2 (95% CI: 7.5-19.8)
      for smokers with hypertension, 5.3 (CI:3.3-8.1) for smokers with normal blood
      pressure and 2.4 (CI:1.4-4.3) for never-smokers with hypertension (reference:
      normotensive never-smokers). The corresponding RRs for diabetic smokers and
      diabetic never-smokers were 19.0 (CI: 10.2-35.4) and 8.8 (CI: 4.4-17.4),
      respectively (reference: nondiabetic never-smokers). In terms of attributable
      risks, hypertension, hypercholesterolaemia and diabetes accounted for 12.9, 11.5
      and 7.2%, respectively, of MI in female smokers. Low socio-economic level and
      being unmarried accounted for 19.6 and 1.6%, respectively. CONCLUSIONS: Although
      smoking is a major risk factor for MI, the risk varies widely between women with
      similar tobacco consumption. The results illustrate the need of a global risk
      factor assessment in female smokers and suggest that female smokers should be
      targets both for intensified risk factor management and programmes to stop
      smoking.

PMID- 15257724
TI  - Low-grade inflammation, endothelial activation and carotid intima-media thickness
      in type 2 diabetes.
AB  - OBJECTIVES: The objective of this study was to assess the relationship between
      inflammation, endothelial activation and incipient atherosclerosis in type 2
      diabetes. DESIGN: Cross-sectional study. Setting and subjects. We studied 239
      type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78
      healthy control subjects, aged 50-75 in a single research centre. METHODS:
      Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating
      intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin,
      ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6,
      monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A(2)
      type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured. RESULTS:
      Carotid IMT was significantly thicker in diabetic patients than healthy controls
      across the whole age range. IMT was also thicker in diabetic patients with, than
      without, CVD, but this difference disappeared after controlling for confounding
      factors. Concentrations of the inflammatory and endothelial markers except IL-6
      were significantly higher in the diabetic patients than in healthy controls, but
      comparable in diabetic patients with and without CVD. The main determinants of
      IMT in the diabetic patients were blood pressure, age and diabetes duration.
      CONCLUSIONS: Low-grade inflammation and endothelial activation are increased in
      diabetic patients but do not associate with IMT or clinical CVD. The inflammatory
      reaction seems to be rather a feature of the metabolic syndrome than a direct
      determinant of atherosclerosis.

PMID- 15257725
TI  - Leptin, but not adiponectin, predicts stroke in males.
AB  - OBJECTIVE: To test whether leptin and adiponectin are risk markers for a first
      ever stroke. RESEARCH DESIGN, METHODS AND SUBJECTS: A nested case-referent study
      identified 276 cases with first-ever stroke (234 cases with ischaemic and 42 with
      haemorrhagic stroke). Prior to the stroke, they had participated in population
      based health surveys in northern Sweden (median time between survey and stroke
      was 4.9 years). Referents were matched for sex, age, date and type of health
      survey, and geographical region. Putative risk markers for first-ever stroke,
      including blood pressure (BP), diabetes, smoking, body mass index (BMI),
      cholesterol, leptin, and adiponectin, were analysed by conditional logistic
      regression analysis. RESULTS: Increased BMI, high cholesterol and fasting glucose
      levels, diabetes mellitus and hypertension were found in future stroke patients.
      Whereas leptin levels were higher in male subjects (P = 0.004), adiponectin did
      not differ between groups. A high leptin level independently predicted stroke in
      men (OR = 2.46; 95% CI 1.08-5.62) but not in women. Adiponectin levels did not
      predict stroke. Males with high leptin levels developed stroke faster than males
      with low leptin levels (P = 0.0009), independently of traditional risk factors.
      CONCLUSIONS: Leptin may be an important link to the development of
      cerebrovascular disease in men, whereas adiponectin does not associate with
      future stroke.

PMID- 15257726
TI  - Improving the outcomes of anticoagulation: an evaluation of home follow-up of
      warfarin initiation.
AB  - OBJECTIVES: A number of studies have reported that the risk of bleeding
      associated with warfarin is highest early in the course of therapy. This study
      examined the effect of a programme focused on the transition of newly
      anticoagulated patients from hospital to the community. DESIGN: Open-label
      randomized controlled trial. SETTING: Home-based follow-up of patients discharged
      from acute care hospital in southern Tasmania, Australia. SUBJECTS: A total of
      128 patients initiated on warfarin in hospital and subsequently discharged to
      general practitioner (GP) care were enrolled in the study. Sixty were randomized
      to home monitoring (HM) and 68 received usual care (UC). INTERVENTIONS: HM
      patients received a home-visit by the project pharmacist and point-of-care
      international normalized ratio (INR) testing on alternate days on 4 occasions,
      with the initial visit two days after discharge. The UC group was solely managed
      by the GP and only received a visit 8 days after discharge to determine
      anticoagulant control. RESULTS: At discharge, 42% of the HM group and 45% of the
      UC group had a therapeutic INR. At day 8, 67% of the HM patients had a
      therapeutic INR, compared with 42% of UC patients (P < 0.002). In addition, 26%
      of UC patients had a high INR, compared with only 4% of HM patients. Bleeding
      events were assessed 3 months after discharge and occurred in 15% of HM patients,
      compared with 36% of the UC group (P < 0.01). CONCLUSIONS: This programme
      improved the initiation of warfarin therapy and resulted in a significant
      decrease in haemorrhagic complications in the first 3 months of therapy.

PMID- 15257727
TI  - Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the
      interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and
      interleukin-18.
AB  - OBJECTIVE: In amyloid A (AA) amyloidosis the receptor for advanced glycation end
      products is a target for the circulating amyloid precursor protein (SAA)
      resulting in upregulation of the proinflammatory cytokine pathway. Besides
      inducing hepatic SAA synthesis the interleukin-1 cytokine family is involved in
      the regulation of haematopoiesis. We therefore studied the relationship between
      the circulating levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL
      18), a new member of the IL-1 complex, as well as polymorphisms within the IL-1
      cluster with the occurrence of anaemia in patients with AA amyloidosis. DESIGN,
      SETTING AND SUBJECTS: The study included 54 adult patients with biopsy-proven
      reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb)
      level: group I included all patients with Hb < 110 g L(-1) (n = 16); group II
      patients (Hb > 110 g L(-1), n = 16) were selected to match group I patients with
      respect to sex, age, underlying disease (seropositive, erosive rheumatoid
      arthritis) and renal function; and group III patients (n = 38) represented all
      patients (unselected) with Hb > or = 110 g L(-1). Gene polymorphisms were studied
      by polymerase chain reaction restriction length assay and included the base
      exchange at position-889 of the IL-1alpha gene, the polymorphic region at
      position-511 and the polymorphic locus at exon 5, position +3954 of the IL-1beta
      gene, as well as the IL-1 receptor antagonist (IL-1Ra) exon 2 polymorphism caused
      by the 86-bp tandem repeats. Plasma IL-1beta, IL-1alpha, IL-18, IL-1 Ra, SAA,
      ferritin, soluble transferrin receptor and erythropoietin levels were studied by
      enzyme immunoassays. RESULTS: Circulating IL-beta and IL-18 were significantly
      raised in the anaemic patients with AA amyloidosis when compared with group II
      patients (matched, Hb > 110 g L(-1)) as well as group III patients (nonmatched,
      Hb > or = 110 g L(-1)). A significant inverse relationship was found between IL
      1beta and haemoglobin levels, as well as between IL-18 and haemoglobin levels.
      The frequency of allele 2 (T) of the IL-1beta-511 promoter gene was significantly
      increased and that of allele 1 (C) decreased in anaemic amyloid patients (group
      I) when compared with group II and III patients. Circulating IL-1beta levels
      tended to be higher amongst the IL-1beta-511 allele 2 carriers than amongst the
      noncarriers, as well as amongst the anaemic amyloid patients filling all criteria
      of anaemia of chronic disease. CONCLUSION: The occurrence of anaemia in patients
      with AA amyloidosis is associated with allele 2 (T) of the IL-1beta-511 promoter
      gene and elevated levels of circulating IL-1beta and IL-18. In AA amyloidosis the
      raised cytokine levels may generate a vicious cycle leading to accelerated
      amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying
      inflammatory disorder.

PMID- 15257728
TI  - Suspicion of pulmonary embolism in outpatients: nonspecific chest pain is the
      most frequent alternative diagnosis.
AB  - OBJECTIVES: Several recent studies have focused on identifying clinical
      predictors of embolism. However, although pulmonary embolism is ruled out in 70
      85% of the patients in whom it is suspected, data on the clinical characteristics
      and discharge diagnosis of such patients are scarce. Our aim was to evaluate
      whether clinical characteristics would allow predicting alternative diagnoses
      other than pulmonary embolism thereby ruling out venous thromboembolism. DESIGN:
      Retrospective analysis. SETTING: Emergency centres of two teaching and general
      hospitals. SUBJECTS: A total of 1090 consecutive outpatients admitted for
      clinically suspected pulmonary embolism and a diagnosis established by a
      validated algorithm and a 3-month follow-up. OUTCOMES: Discharge diagnoses of
      patients in whom pulmonary embolism was ruled out were identified and regrouped
      into two categories: (i) nonspecific chest pain and (ii) diagnosis other than
      pulmonary embolism. Predictive accuracy of clinical and laboratory variables for
      diagnosing nonspecific chest pain was assessed by univariate and multivariate
      analysis. RESULTS: In patients without pulmonary embolism, nonspecific chest pain
      (parietal chest pain, chest pain of unknown origin and pleuritis) was the most
      frequent discharge diagnosis (n = 334, 31% of the entire cohort, 43% of the
      patients without pulmonary embolism). Other patients without pulmonary embolism
      had a wide variety of diagnoses, of which the most frequent were bronchopneumonia
      (6.0% of the entire cohort) and heart failure (5.2%). In the multivariate
      analysis, seven variables were strongly associated with nonspecific chest pain:
      younger age (below 40 years), female gender, respiratory rate below 20 min(-1),
      heart rate below 100 min(-1), and absence of recent immobilization, dyspnoea and
      haemoptysis. Two of the 24 patients in whom all those characteristics were
      present had pulmonary embolism (8%, 95% CI 3-22%). CONCLUSIONS: The most frequent
      discharge diagnosis in emergency ward patients in whom pulmonary embolism is
      ruled out is nonspecific chest pain. A clinical model did not allow to predict
      nonspecific chest pain with enough accuracy to rule out pulmonary embolism
      without further testing. Whether a more precise characterization of chest pain
      might allow an accurate identification of such patients deserves further study.

PMID- 15257729
TI  - Trends in the incidence of chronic Philadelphia chromosome negative (Ph-)
      myeloproliferative disorders in the city of Goteborg, Sweden, during 1983-99.
AB  - OBJECTIVE: In the literature the incidence rates for the chronic Philadelphia
      chromosome negative (Ph-) myeloproliferative disorders (MPD) are known to vary
      extensively; only a few studies have, however, been concerned with incidence
      trends over time. Therefore, the aim of the present work was to investigate
      possible trends as regards incidence rates over time for Ph-MPD. DESIGN: Herein,
      we carried out a retrospective population-based survey on the incidence of
      polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic
      myelofibrosis (IMF), in the city of Goteborg (Sweden), covering the years 1983
      99. RESULTS: The study comprised 416 patients with Ph-MPD. There were 205
      patients with PV, 153 patients with ET, 34 with IMF and 24 with unclassified MPD.
      The annual incidence for PV was 1.97 per 10(5) inhabitants; the corresponding
      figures for ET and IMF were 1.55 per 10(5) and 0.30 per 10(5) inhabitants,
      respectively. There was a significant increase in the annual incidence rate for
      ET (P = 0.008); this increase was significant for male subjects (P = 0.015) but
      did not reach significance for females (P = 0.118). No such increase over time
      was recorded as regards PV and IMF. CONCLUSIONS: The increasing annual incidence
      rate for ET is most possibly explained by the more frequent use of automated
      platelet counts whenever a patient consults a doctor. Thereby, an increasing
      number of patients with overt thrombocytosis of unknown origin are discovered and
      will be referred to specialists within the field of haematology for a correct
      diagnosis.

PMID- 15257731
TI  - Neurological symptoms in a traveller returning from Central America.

PMID- 15257730
TI  - A patient with TSC1 germline mutation whose clinical phenotype was limited to
      lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) can occur as in isolated form
      (sporadic LAM) or as a pulmonary manifestation of tuberous sclerosis complex
      (TSC) (TSC-associated LAM). Recent studies, however, revealed that both forms of
      LAM are genetically related but that sporadic LAM is a distinct clinical entity
      caused by somatic mutations of TSC2 (not TSC1) rather than a forme fruste of TSC
      carrying either of the TSC1 or TSC2 germline mutations. METHOD: Case presentation
      and in-depth molecular and histopathological examinations. A 34-year-old Japanese
      woman was diagnosed as having pulmonary lymphangioleiomyomatosis (LAM) when
      bilateral pneumothoraces were surgically treated in 1992. Although slowly
      progressive renal disfunction was observed due to bilateral multiple renal cysts
      during the past 4 years, she had no other clinical features of TSC and was
      diagnosed as having sporadic LAM with multiple renal cysts of undetermined
      aetiology. Her subsequent clinical course was complicated by an endobrochial
      carcinoid tumour, which eventually resulted in her death in June 1999 due to
      massive haemoptysis. RESULTS: Postmortem examination revealed the presence of LAM
      lesions in the lungs, mediastinal lymph nodes, kidneys and uterus. Diffuse renal
      LAM lesions are presumed to generate multiple renal cysts by constricting the
      nephron rather than epithelial hyperplasia obstructing lumina, which is analysis
      of the TSC genes demonstrated that she did not have TSC2/PKD1 contiguous gene
      syndrome but had a TSC1 germline mutation (Sato T et al. J Hum Genet 2002; 47: 20
      8) that had occured de novo. CONCLUSION: This patient therefore illustrates that
      clinical manifestations of TSC are sufficiently diverse as to allow a forme
      fruste of TSC that mimics sporadic LAM and that TSC1 mutation can cause multiple
      renal cysts resulting in renal failure.

PMID- 15257732
TI  - Only one of four patients with familial hypercholesterolaemia reach cholesterol
      treatment goals in primary prevention.

PMID- 15257733
TI  - Locally delivered doxycycline improves the healing following non-surgical
      periodontal therapy in smokers.
AB  - OBJECTIVE: The outcome of non-surgical periodontal therapy is known to be
      inferior in smokers compared to non-smokers. In the present study, the question
      was asked whether such a difference in healing response may be less evident
      following adjunctive use of locally delivered controlled-release doxycycline.
      METHODS: One hundred and three patients (42 smokers, 61 non-smokers), each having
      at least eight periodontal sites with PPD (probing pocket depth) > or =5 mm, were
      following stratification for smoking randomly assigned to two different treatment
      protocols; non-surgical scaling/root planing (Control) or ultrasonic
      instrumentation+application of a 8.5% w/w doxycycline gel (Atridox trade mark )
      (Test). Instructions in oral hygiene were given to all patients. Clinical
      examinations of plaque, PPD, clinical attachment level (CAL) and bleeding
      following pocket probing were performed at baseline and after 3 months. Primary
      efficacy endpoints were changes in PPD and CAL. Patient mean values were
      calculated as basis for statistical analysis (multiple regression analyses).
      RESULTS: The baseline examination revealed no significant difference in mean PPD
      between treatment groups or between smokers and non-smokers (mean PPD 5.7-5.9
      mm). The mean PPD reduction in the control group at 3-month was 1.1 mm (SD=0.45)
      for smokers and 1.5 mm (0.67) for non-smokers. In the test group the PPD
      reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non-smokers,
      respectively. The mean CAL gain for smokers and non-smokers amounted to 0.5 mm
      (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm
      (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression
      analysis revealed that smoking and initial PPD negatively influenced the
      treatment outcome in terms of PPD reduction and CAL gain, while the use of
      doxycycline had a significant positive effect. CONCLUSION: Locally applied
      controlled-release doxycycline gel may partly counteract the negative effect of
      smoking on periodontal healing following non-surgical therapy.

PMID- 15257734
TI  - A model of periodontitis in the rat: effect of lipopolysaccharide on bone
      resorption, osteoclast activity, and local peptidergic innervation.
AB  - OBJECTIVE: To establish and characterise a rat model of periodontitis that
      reiterates the features of human disease. METHODS: Periodontal inflammation was
      induced by a single injection of 10 microg liposaccharide (LPS) (Salmonella
      typhimurium) in 1 microl saline into rat mandibular gingiva at the buccomesial
      aspect of the second molar. Animals were killed after 3, 7 and 10 days, mandibles
      dissected and sectioned for histological and immunocytochemical analysis.
      RESULTS: LPS injection resulted in a significant gingival and periodontal
      inflammation with inflammatory infiltrate, apical migration of the junctional
      epithelium, interdental bone loss, and activation of osteoclasts at the site of
      injection 7 and 10 days after injection. At 10 days post injection, there was a
      significant trend for bone loss on both sides of the mandible. Periodontal
      inflammation was associated with alteration in the levels of calcitonin gene
      related peptide-like immunoreactivity in nerve terminals innervating the inflamed
      gingival papilla. CONCLUSION: Intragingival injection of LPS in the rat provides
      an easily induced reproducible experimental model of periodontal inflammation
      that reiterates features of human disease.

PMID- 15257735
TI  - Healing of intrabony defects following surgical treatment with or without an
      Er:YAG laser.
AB  - AIM: The aim of this controlled, parallel design clinical study was to compare
      the healing of intrabony periodontal defects following treatment with access flap
      surgery with and without debridement with an Er:YAG laser. METHODS: Twenty-three
      patients each of whom exhibited one deep intrabony defect were randomly treated
      with either access flap surgery followed by root surface and defect debridement
      using an Er:YAG laser (KEY3) (160 mJ, 10 Hz) (test), or with access flap surgery
      followed by root surface and defect debridement using hand and ultrasonic
      instruments (control). The following clinical parameters were recorded at
      baseline and at 6 months: plaque index; gingival index; bleeding on probing;
      probing depth (PD); gingival recession; and clinical attachment level (CAL). The
      primary outcome variable was CAL. No statistically significant differences
      between the groups were found at baseline. RESULTS: No serious adverse events
      were observed after any of the treatments. The results have shown that in the
      test group the PD decreased from 7.8+/-1.3 to 4.1+/-1.3 mm (p<0.001) and the CAL
      changed from 9.8+/-2.9 to 7.2+/-2.5 mm (p<0.001). In the control group the PD
      decreased from 7.8+/-0.8 to 4.6+/-1.6 mm (p<0.001) and the CAL changed from 9.2+/
      1.2 to 7.7+/-1.6 mm (p<0.01). The test group displayed a higher tendency for CAL
      gain, although this tendency did not prove to be statistically significant.
      CONCLUSION: Within the limits of the present study, it can be concluded that: (i)
      at 6 months following treatment both therapies led to significant improvements of
      the investigated clinical parameters, and (ii) an Er:YAG laser may represent a
      suitable alternative for defect and root surface debridement in conjunction with
      periodontal surgery.

PMID- 15257736
TI  - The effect of a chlorhexidine regimen on de novo plaque formation.
AB  - OBJECTIVE: To evaluate the effect of a pretreatment regimen that combined
      meticulous mechanical tooth cleaning with the daily use of chlorhexidine (rinse,
      gargle and tongue application) on de novo plaque formation and on the
      recolonization of various microbiological species in plaque and saliva during a 4
      day period of no oral hygiene. MATERIAL AND METHODS: Ten subjects aged 24-36
      years with gingivitis were recruited. The study was designed as a double blind
      cross-over clinical trial including two phases. Each experimental phase comprised
      one preparatory period of 7 days and one plaque accumulation period of 4 days.
      During the preparatory period, the volunteers (i) performed meticulous mechanical
      tooth cleaning using toothbrush and dentifrice and (ii) were, in addition, given
      two sessions of professional tooth cleaning (PTC) The final PTC was delivered
      after bacterial sampling had been made on Day 0. In the Control group, no
      additional plaque control measures were included. In the Test group, the
      participants in addition to the mechanical measures (i) rinsed twice daily, for
      60 s each time with a 0.2% chlorhexidine solution, (ii) gargled twice daily for
      10 s with the chlorhexidine preparation, and finally (iii) brushed the dorsum of
      the tongue for 60 s, twice daily, with a 1.0% chlorhexidine gel. During the 4-day
      plaque accumulation period, the participants abstained from all mechanical and
      chemical plaque control measures. On Days 0, 1, 2 and 4 the quantity and quality
      of plaque formed was assessed by clinical means and by DNA probe techniques. The
      microbiota of the saliva was studied in samples obtained on Days 0 and 4.
      RESULTS: It was demonstrated that chlorhexidine used as a mouthrinse combined
      with gargling and tongue application during the preparatory period significantly
      retarded the amount of plaque that formed on tooth surfaces during the following
      4 days of no oral hygiene. Further, the number of microorganisms present in the
      biofilm representing Days 0, 1 and 2 of the "plaque accumulation period" was
      apparently affected by the use of the antiseptic. Among the microorganisms
      influenced by the chlorhexidine regimen, a substantial number belonged to the
      genus Actinomyces. It was also observed that the adjunctive use of chlorhexidine
      reduced the number of bacteria present in saliva at the end of the preparatory
      period (i.e. on Day 0). After 4 days of no oral hygiene, the microbiota of the
      newly formed plaque in the Test and Control groups had many features in common.
      CONCLUSION: Habitat is critical in controlling the bacterial composition of the
      dental biofilm. The microbiota will tend to go back to the one that is
      characteristic of a given subject, once chemical antimicrobial means are
      withdrawn.

PMID- 15257737
TI  - The short-term effectiveness of non-surgical treatment in reducing protease
      activity in gingival crevicular fluid from chronic periodontitis patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the short-term effect of non
      surgical periodontal treatment on protease activity in gingival crevicular fluid
      (GCF) of patients with chronic periodontitis. MATERIAL AND METHODS: After
      clinical examination, in which pocket probing depth, probing attachment level,
      plaque and bleeding indices were recorded, gingival fluid samples from 21 chronic
      periodontitis patients were collected from gingivitis (GP) and periodontitis (PP)
      sites with an intracrevicular washing method. Samples were taken in the same way
      from a group of patients with gingivitis alone (GG). The periodontitis patients
      received non-surgical periodontal treatment and were re-evaluated 30 days later.
      We compared elastase and collagenase activities before and after treatment. The
      former activity was measured with a low-weight substrate (S-2484) and inhibited
      by alpha-1-antitrypsin. Matrix-metalloproteinase-8 (MMP-8) was measured with an
      ELISA and collagenolytic activity with fluorescein-conjugated collagen type I as
      substrate. RESULTS: All clinical parameters showed a significant improvement
      after treatment (p<0.05) which was accompanied by a significant reduction in the
      values of total elastase activity, free elastase, MPP-8 and collagenolytic
      activity in both GP and PP sites (p<0.05). However, the latter sites continued to
      have higher levels of MMP-8 and collagenolytic activity than the former ones
      after treatment. The free elastase activity and the proportion of free elastase
      in GP and PP samples after treatment remained higher than in untreated GG
      samples. CONCLUSION: This study shows that the clinical improvements after non
      surgical treatment are accompanied by reductions in protease and neutrophil
      activities.

PMID- 15257738
TI  - High and low brushing force in relation to efficacy and gingival abrasion.
AB  - OBJECTIVES: Does a high brushing force induce more gingival abrasion than a low
      (regular) brushing force? Furthermore, what is the effect of a low or high force
      on the efficacy? METHODS: Thirty-five non-dental students were selected. All
      received an appointment prior to which they abstained from oral hygiene for at
      least 48 h. At baseline the teeth and surrounding tissues were disclosed using
      Mira-2-Tone disclosing solution. Next, the examiner (PAV) evaluated the number of
      sites with gingival abrasion and the amount of dental plaque (Quigley & Hein) at
      6 surfaces of each tooth. In the absence of this examiner, the subject's teeth
      were brushed by a hygienist (MP) using the Braun/Oral-B-D17 oscillating rotating
      toothbrush. Brushing was performed in two randomly selected contra-lateral
      quadrants for 60 s with either a low force (+/-1.5 N) or high force (+/-3.5 N)
      and in the opposing quadrants for 60 s with the alternative force. Visual
      feedback was given to control force. The brush was moved from the distal tooth to
      the central incisor perpendicular to the tooth surface with an angle of
      approximately 10-15 degrees towards the gingival margin. Next, the number of
      sites with abrasion and the remaining plaque were assessed again. RESULTS: The
      overall baseline gingival abrasion scores were 3.1 and 3.2 sites for high and low
      force, respectively, and increased to 5.0 and 5.9 sites respectively after
      brushing. There was no significant difference with respect to incidence of
      abrasion. At baseline, 48 h. plaque levels were 2.2. The reduction in plaque
      scores with the low force was 60% and with the high force 56%. This difference
      was significant. CONCLUSION: With the oscillating rotating power toothbrush
      (Braun/Oral-B D17) the use of high force (+/-3.5 N) is less efficacious as
      compared to a regular low force (+/-1.5 N) while the incidence of gingival
      abrasion sites was comparable.

PMID- 15257739
TI  - The association of periodontal disease parameters with systemic medical
      conditions and tobacco use.
AB  - OBJECTIVES: The objective of this study was to determine if an association
      existed between periodontal disease and various systemic medical conditions and
      tobacco use. MATERIAL AND METHODS: The study design was a case-controlled,
      retrospective chart review. Patient charts (n=2006) were selected from more than
      13,000 active patients attending the University of Minnesota dental clinics.
      These charts were examined to determine patient's self-reported systemic
      condition and smoking history. In addition, the number of missing teeth and bone
      loss were recorded. Two examiners collected the data. One examiner abstracted
      patient's medical history from the standard clinic medical questionnaire. The
      second examiner assessed the radiographs and dental charts to determine bone loss
      and number of missing teeth. Each examiner was blind to the findings of the
      other. RESULTS: After adjusting for age, sex, diabetes and smoking (yes/no)
      status, seven conditions were significantly (p=0.0003-0.04) related to bone loss
      or number of missing teeth (vascular disease, heart surgery, vascular surgery,
      heart attack, thyroid problems, arthritis, stomach ulcers). From these
      conditions, thyroid problems and arthritis had a negative association with bone
      loss. CONCLUSIONS: These findings support the results from previous investigators
      that a number of systemic conditions and smoking are closely associated with
      missing teeth or bone loss.

PMID- 15257740
TI  - Association of periodontal disease to anxiety and depression symptoms, and
      psychosocial stress factors.
AB  - OBJECTIVE: A cross-sectional study was conducted to investigate if anxiety,
      depression and hopelessness symptoms are associated with periodontal disease.
      METHOD: A total of 160 subjects took part in this study. Probing depth and
      clinical attachment level were recorded at six sites per tooth and the gingival
      and plaque indices were also recorded. The instruments used to assess the
      psychological variables (anxiety, depression, stress, psychiatric symptoms and
      hopelessness) were: the State-Trait Anxiety Inventory, the Beck Depression
      Inventory, the Life Events Scale modified by Savoia, the Self-Report Screening
      Questionnaire-20 and the Beck Hopelessness Scale. RESULTS: There was no
      difference in scale score means between patients with and without established
      periodontitis. Results of the Ordinal Logistic Regression Analysis model that
      included age, plaque index, smoking and psychological factors showed that
      patients with psychiatric symptoms (odds ratio (OR) 1.24, 95% confidence interval
      (CI) 0.33-4.78), depression symptoms (OR 0.57, 95% CI 0.15-2.21) and with
      hopelessness (OR 0.70, 95% CI 0.13-3.84) were not at a greater risk of developing
      established periodontitis. CONCLUSION: In this sample, no evidence was found for
      an association between depression, hopelessness, psychiatric symptoms and
      established periodontitis. The association of periodontal disease to depression,
      anxiety and stress should be investigated in psychiatric populations, especially
      in those with depression and anxiety disorders.

PMID- 15257741
TI  - The electric toothbrush: analysis of filaments under stereomicroscope.
AB  - BACKGROUND: The use of manual and electric toothbrushes has a fundamental role in
      primary prevention in oral hygiene. However, aggressive use of the toothbrush,
      especially those with non-rounded filaments, can result in lesions in both soft
      and hard oral tissue. Without doubt, the electric toothbrush is a useful aid for
      the patient, and it is therefore interesting to evaluate not only its
      effectiveness in plaque removal, but also the relationship between morphology of
      filaments and incidence of muco-gingival pathologies. OBJECTIVE: The aim of this
      research was to evaluate various forms of bristles of electric toothbrushes under
      a stereomicroscope vision. DATA SOURCES: Brushes tested included two samples of
      toothbrushes from six different types. Tufts from the same position on the
      toothbrush head were removed and examined under stereomicroscope. In this study
      the percentage of rounded filaments that is considered acceptable and non
      traumatic was evaluated according to the Silverstone and Featherstone
      classification. CONCLUSIONS: Morphological analysis of electric toothbrush
      filaments revealed a low percentage of rounded filaments. In only four of 12
      electric toothbrushes tested there were more than 50% of the filaments rounded in
      appearance.

PMID- 15257742
TI  - Baseline radiographic defect angle of the intrabony defect as a prognostic
      indicator in regenerative periodontal surgery with enamel matrix derivative.
AB  - INTRODUCTION: The baseline radiographic defect angle has previously been
      correlated with the clinical outcomes of intrabony defects treated with access
      flap or guided tissue regeneration. The aim of this study was to investigate
      whether an association exists between baseline radiographic defect angle and
      treatment outcome when enamel matrix derivative (EMD) is used in periodontal
      regenerative surgery. MATERIALS AND METHODS: Baseline radiographs were collected
      from the test group of a previously published clinical trial using a population
      of 166 patients treated for chronic periodontitis. All intrabony defects were >
      or =3 mm for inclusion in the original study. Either modified or simplified
      papilla preservation technique was used to access the defect. The roots were
      conditioned with an EDTA gel and the primary outcome measure was clinical
      attachment level (CAL) change, 1 year after surgery. RESULTS: Sixty-seven
      radiographs were measurable. The probability of obtaining CAL gain >3 mm was 2.46
      times higher (95% confidence interval: 1.017-5.970) when the radiographic defect
      angle was < or =22 degrees than when it was > or =36 degrees. CONCLUSIONS: This
      study showed that there was a significant association between baseline
      radiographic defect angle and CAL gain at 1 year. The observed increased odds
      ratio of obtaining CAL gain of > or =4 mm after regenerative surgery with EMD is
      used in narrow (< or =22 degrees ) intrabony defects, suggests that the baseline
      radiographic defect angle might be used as a prognostic indicator of treatment
      outcome.

PMID- 15257743
TI  - Therapy with adjunctive doxycycline local delivery in patients with type 1
      diabetes mellitus and periodontitis.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of subgingival
      administration of doxycycline as an adjunct to periodontal therapy in type 1
      diabetes mellitus (DM) patients. MATERIAL AND METHODS: Twenty-two paired
      periodontal defects > or =5.0 mm were treated in 11 patients (35-55 years old).
      After initial therapy the sites were randomly assigned into test (scaling and
      root planing+subgingival administration of 10% doxycycline hyclate gel) or
      control (scaling and root planing+subgingival placebo gel) groups. The clinical
      parameters of clinical attachment level (CAL), probing depth (PD) and gingival
      margin level (GML) for recession determination were assessed at baseline, after 6
      weeks, and 6, 9 and 12 months, using a computerized probe. Data were
      statistically evaluated using Duncan and F tests. RESULTS: Between study group
      comparisons indicated PD reduction and CAL gain were greater in the test group
      than in the control group at 6 weeks and 6, 9 and 12 months but only
      statistically significant at 12 months (p<0.05). Within study group comparisons
      indicated statistically significant differences were found for CAL and PD values
      favouring the adjunctive doxycycline group from baseline to 6 weeks and 6, 9 and
      12 months (p<0.05). CONCLUSIONS: These findings suggest that subgingivally
      delivered doxycycline hyclate produces additional favorable clinical results to
      periodontal therapy in type 1 DM patients.

PMID- 15257744
TI  - Effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on
      regeneration of periodontal attachment following tooth replantation in dogs.
AB  - OBJECTIVES: Subcutaneous and intramuscular implants of bone morphogenetic protein
      12 (BMP-12) have been shown to induce formation of tendon and ligament tissue.
      BMP-12 induced a new attachment with a distinct fibrocartilaginous zone at the
      tendon-bone interface in the rat tendon-bone attachment model. Surgical controls
      showed poor healing and failure to reform the appropriate tendon-bone attachment
      morphologically. Application of recombinant human BMP-12 (rhBMP-12) to
      periodontal defects suggests that rhBMP-12 has the potential to support
      regeneration of the periodontal ligament (PDL). The objective of this pilot study
      was to evaluate this effect of rhBMP-12 in a tooth replantation model. METHODS:
      Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or
      mandibular incisor and premolar teeth were extracted and the PDL was either left
      "intact" or removed by root planing. rhBMP-12 (1.0 mg/ml) or a buffer control was
      topically applied to teeth with "intact" PDL in contralateral jaw quadrants in
      each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP-12 or the
      buffer solution for 10 min and then replanted. The remaining three animals
      received rhBMP-12 (1.0 mg/ml) and the buffer control in a similar fashion applied
      to teeth instrumented to remove the PDL and cementum, and surface demineralized
      with citric acid. The animals were euthanized at 8 weeks postsurgery and block
      sections were collected and processed for histopathologic analysis. RESULTS: No
      dramatic differences were found between teeth receiving topical rhBMP-12 and the
      buffer control. Application of rhBMP-12 did not have an apparent effect on new
      cementum and PDL formation in the tooth replantation model. Moreover, application
      of rhBMP-12 did not increase nor did it decrease the apparent presence and extent
      of ankylosis along the root surface compared to the control. CONCLUSIONS: The
      observations from this study do not support the use of topical rhBMP-12 to
      support the reestablishment of the PDL including regeneration of cementum and
      functionally oriented fibers, and to prevent ankylosis and root resorption
      following replantation of teeth.

PMID- 15257745
TI  - Periodontal repair in dogs: effect of recombinant human bone morphogenetic
      protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal
      attachment.
AB  - OBJECTIVES: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been
      shown to stimulate alveolar bone and cementum formation in periodontal defects
      but not a functionally oriented periodontal ligament (PDL). Subcutaneous and
      intramuscular implants of BMP-12 have been shown to induce tendon formation and
      ligament-like tissue. The objective of this study was to evaluate rhBMP-12 for
      periodontal regeneration, in particular PDL formation. METHODS: Six young adult
      Hound Labrador mongrel dogs were used. Routine supraalveolar periodontal defects
      were created around the mandibular premolar teeth. Three animals received rhBMP
      12(0.04 mg/ml) in an absorbable collagen sponge (ACS) carrier vs. rhBMP-12(0.2
      mg/mL)/ACS in contralateral defects. Three animals received rhBMP-12(1.0
      mg/ml)/ACS vs. rhBMP-2(0.2 mg/ml)/ACS (total implant volume/defect approximately
      1 ml). The animals were euthanized 8 weeks postsurgery and block biopsies were
      processed for histometric analysis. RESULTS: Bone regeneration appeared increased
      in sites receiving rhBMP-2/ACS compared to sites receiving rhBMP-12/ACS. Cementum
      regeneration was similar comparing sites implanted with rhBMP-2/ACS to sites
      implanted with rhBMP-12/ACS. In contrast, sites receiving rhBMP-12/ACS exhibited
      a functionally oriented PDL bridging the gap between newly formed bone and
      cementum whereas this was a rare observation in sites receiving rhBMP-2/ACS.
      Ankylosis appeared increased in sites receiving rhBMP-2/ACS compared to those
      receiving rhBMP-12/ACS. CONCLUSIONS: The outcomes of this study suggest that
      rhBMP-12 may have significant effects on regeneration of the PDL. Additional
      preclinical evaluation is needed to confirm these initial observations prior to
      clinical application.

PMID- 15257746
TI  - Matrix metalloproteinases, their physiological inhibitors and osteoclast factors
      are differentially regulated by the cytokine profile in human periodontal
      disease.
AB  - OBJECTIVE: Inflammatory reactions raised in response to periodontopathogens are
      thought to trigger pathways of periodontal tissue destruction. We therefore
      investigated the expression of matrix metalloproteinases (MMPs) and the
      osteoclastogenic factor receptor activator of nuclear factor-kappaB ligand
      (RANKL), their respective tissue inhibitors of metalloproteinases (TIMPs) and
      osteoprotegerin (OPG) in different forms of human periodontal diseases (PDs), and
      the possible correlation with the expression of inflammatory and regulatory
      cytokines. MATERIAL AND METHODS: Quantitative polymerase chain reaction (real
      time PCR) was performed with gingival biopsies mRNA from aggressive (AP) and
      chronic periodontitis (CP) patients. RESULTS: Periodontitis patients exhibit
      higher expression of all analyzed factors when compared with healthy tissues. The
      expression of MMPs and RANKL were similar in AP and CP, as well as the expression
      of TNF-alpha. On the other hand, the expression of TIMPs and OPG was higher in
      CP, and was associated with lower IFN-gamma and higher IL-10 expression, compared
      with AP. CONCLUSION: It is possible that the pattern of cytokines expressed
      determines the stable or progressive nature of the lesions and regulates the
      severity of PD, driving the balance between MMPs and TIMPs, RANKL and OPG
      expression in the gingival tissues controlling the breakdown of soft and bone
      tissues and, consequently, the disease severity.

PMID- 15257747
TI  - A longitudinal study of the relationship between periodontal disease and bone
      mineral density in community-dwelling older adults.
AB  - OBJECTIVE: Bone loss is a common feature of periodontitis and osteoporosis. Both
      diseases may share common etiologic agents which may either affect or modulate
      the process of both diseases. The purpose of this study was to evaluate the
      relationship between systemic bone mineral density (BMD) and periodontal disease
      among older people. MATERIALS AND METHODS: Among all 4,542 inhabitants aged 70
      years according to a registry of residents in Niigata city in Japan, 600 people
      were selected randomly. One hundred and eighty-four subjects who did not have
      diabetes mellitus, whose blood sugar was <140 mg/dl, who had more than 20 teeth,
      who were non-smokers, and who did not take medication for osteoporosis, were
      included in the study. Four dentists performed clinical evaluations on probing
      attachment level (PAL). We also utilized the data on BMD of the heel, which we
      measured using an ultrasound bone densitometer. Follow-up clinical surveys were
      done by measuring PAL after 3 years. Finally, 179 subjects who could participate
      in both the baseline and the follow-up examinations were included in the
      analysis. After dividing the subjects into an osteopenia group (OG) and non
      osteopenia group (NOG), we evaluated the relationship between BMD and the number
      of progressive sites which had > or =3 mm additional attachment loss during 3
      years after controlling the known confounding factors. RESULTS: The mean number
      of progressive sites for the OG and the NOG, respectively, were 4.65+/-5.51 and
      3.26+/-3.01 in females and 6.88+/-9.41 and 3.41+/-2.79 in males. Two-way analysis
      of variance was performed to discriminate among effects of gender, BMD, and
      gender-BMD interaction. A significant effect of BMD (OG or NOG, p=0.043) with a
      significant interaction (p=0.038) was observed. Furthermore, BMD was associated
      with the number of progressive sites which had > or =3 mm additional attachment
      loss during the 3 years (p=0.001) by multiple linear regression analysis.
      CONCLUSIONS: This study suggested that there was a significant relationship
      between periodontal disease and general BMD.

PMID- 15257748
TI  - Genetic variations in the matrix metalloproteinase-1 promoter and risk of
      susceptibility and/or severity of chronic periodontitis in the Czech population.
AB  - OBJECTIVES: Matrix metalloproteinase-1 (MMP-1) is a potent enzyme degrading
      extracellular matrix that was implicated in the pathogenesis of chronic
      periodontitis. Therefore, the aim of our study was to examine the association
      between three promoter polymorphisms of the MMP-1 gene and chronic periodontitis
      susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A
      total of 329 Caucasian subjects were enrolled in this study. They were 133
      patients with mild to severe chronic periodontitis and 196 unrelated control
      subjects. MMP-1 promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were
      genotyped using standard polymerase chain reaction-restriction fragment length
      product methods. RESULTS: Genotype analysis of the three single nucleotide
      polymorphisms across 27 different combinations showed significant association
      with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed
      no differences in distribution of the -519A/G and -422A/T variants between
      periodontitis and control groups. However, a trend to increased frequency of the 
      1607 1G allele was observed in patients with chronic periodontitis compared with
      the controls (p=0.054). When the groups were further stratified by smoking
      status, the 1G allele was associated with chronic periodontitis among non-smokers
      but not among smokers (p=0.033). On the contrary, the distribution of genotype
      frequencies of the MMP-1 -422A/T polymorphism was different between the patient
      and control smokers with respect to heterozygotes (73.91% versus 50.91%;
      p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the MMP
      1 promoter may have only a small effect on the etiopathogenesis of chronic
      periodontitis.

PMID- 15257749
TI  - The anti-plaque efficacy of a chlorhexidine mouthrinse used in combination with
      toothbrushing with dentifrice.
AB  - BACKGROUND: Although the efficacy of chlorhexidine (CHX) chemically can be
      affected by the presence of a sodium lauryl sulphate (SLS)-containing dentifrice
      in the oral cavity, previous data, collected without supervision, showed that the
      level of plaque inhibition offered by a 0.2% CHX post-brushing rinse in one jaw
      is not reduced under the influence of toothbrushing with a 1.5% SLS-containing
      dentifrice in the opposite jaw. OBJECTIVES: The aim of the present study was to
      investigate, during a 4-day supervised study period, the anti-plaque efficacy of
      a 0.2% CHX pre-brushing rinse in one jaw, under the influence of toothbrushing in
      the opposite jaw, either with a SLS-containing dentifrice or with a SLS-free
      dentifrice. Three different dentifrices were tested. Two of them contained SLS
      (Colgate Total & Aquafresh Natural Whitening), the other (Zendium) did not.
      METHODS: The study was an examiner blind, randomised 4-cell, crossover design. It
      used a 4-day plaque accumulation model to compare under supervision 4 different
      oral hygiene regimens with a washout period of at least one week. Thirty-five
      healthy volunteers were enrolled in the study and were randomly assigned to a
      sequence according to a 4 x 4 Latin square design. At the beginning of each 4-day
      test period, they received a thorough dental prophylaxis. Plaque was scored in
      one randomly assigned (upper or lower) jaw, called the study jaw. At the end of
      the 4-day period the study jaw was used to study the effect of the four regimens
      on the level of plaque accumulation. The opposite jaw was assigned as the
      dentifrice jaw and served only to introduce the effect of brushing with a
      dentifrice in the study model. Four oral hygiene regimens were designed. During
      the randomly assigned test periods, rinsing with 0.2% CHX and then brushing the
      dentifrice jaw was performed twice daily. In regimen 1, 2, and 3 the subjects
      used a dentifrice in the assigned dentifrice jaw being either a dentifrice with
      SLS (Colgate Total and Aquafresh Natural Whitening) or a SLS-free dentifrice
      (Zendium). Regimen 4 served as a control during witch subjects only rinsed with
      0.2% CHX. No other oral hygiene methods were allowed. After 4 days of undisturbed
      plaque accumulation, the amount of plaque was evaluated (Lobene et al. 1982,
      Quigley & Hein 1962, Turesky et al. 1970 modifications). RESULTS: The overall
      plaque index for regimen 1, 2 and 3 was, respectively, 1.8, 1.8 and 1.9. For
      regimen 4, the overall plaque index was 1.9. There was no significant difference
      in plaque accumulation between the four regimens. CONCLUSIONS: Within the present
      study design, it can be concluded that the anti-plaque efficacy of a pre-brushing
      0.2% CHX mouthrinse does not seem to be reduced under the influence of a normal
      toothbrushing exercise with a dentifrice after rinsing, whether the dentifrice
      contains SLS or not.

PMID- 15257752
TI  - Impact, regulation and health policy implications of physician migration in OECD
      countries.
AB  - BACKGROUND: In the face of rising demand for medical services due to ageing
      populations, physician migration flows are increasingly affecting the supply of
      physicians in Organisation for Economic Co-operation and development (OECD)
      countries. This paper offers an integrated perspective on the impact of physician
      migration on home and host countries and discusses international regulation and
      policy approaches governing physician migration. METHODS: Information about
      migration flows, international regulation and policies governing physician
      migration were derived from two questionnaires sent to OECD countries, a
      secondary analysis of EUROSTAT Labour Force Surveys, a literature review and
      official policy documents of OECD countries. RESULTS: OECD countries increasingly
      perceive immigration of foreign physicians as a way of sustaining their physician
      workforce. As a result, countries have entered into international agreements
      regulating physician migration, although their success has been limited due to
      the imposition of licensing requirements and the protection of vested interests
      by domestic physicians. OECD countries have therefore adopted specific policies
      designed to stimulate the immigration of foreign physicians, whilst minimising
      its negative impact on the home country. Measures promoting immigration have
      included international recruitment campaigns, less strict immigration
      requirements and arrangements that foster shared learning between health care
      systems. Policies restricting the societal costs of physician emigration from
      developing countries such as good practice guidelines and taxes on host countries
      have not yet produced their expected effect or in some cases have not been
      established at all. CONCLUSIONS: Although OECD countries generally favour long
      term policies of national self-sufficiency to sustain their physician workforce,
      such policies usually co-exist with short-term or medium-term policies to attract
      foreign physicians. As this is likely to continue, there is a need to create a
      global framework that enforces physician migration policies that confer benefits
      on home and host countries. In the long term, OECD countries need to put in place
      appropriate education and training policies rather than rely on physician
      migration to address their future needs.

PMID- 15257753
TI  - Association of sperm protein 17 with A-kinase anchoring protein 3 in flagella.
AB  - BACKGROUND: Sperm protein 17 (Sp17) is a three-domain protein that contains: 1) a
      highly conserved N-terminal domain that is 45% identical to the human type II
      alpha regulatory subunit (RII alpha) of protein kinase A (PKA); 2) a central
      sulphated carbohydrate-binding domain; and 3) a C-terminal Ca++/calmodulin (CaM)
      binding domain. Although Sp17 was originally discovered and characterized in
      spermatozoa, its mRNA has now been found in a variety of normal mouse and human
      tissues. However, Sp17 protein is found predominantly in spermatozoa, cilia and
      human neoplastic cell lines. This study demonstrates that Sp17 from spermatozoa
      binds A-kinase anchoring protein 3 (AKAP3), confirming the functionality of the N
      terminal domain. METHODS: In this study in vitro precipitation and
      immunolocalization demonstrate that Sp17 binds to AKAP3 (AKAP110) in spermatozoa.
      RESULTS: Sp17 is present in the head and tail of spermatozoa, in the tail it is
      in the fibrous sheath, which contains AKAP3 and AKAP4. Recombinant AKAP3 and
      AKAP4 RII binding domains were synthesized as glutathione S-transferase (GST)
      fusion proteins immobilized on glutathione-agarose resin and added to CHAPS
      extracts of human spermatozoa. Western blots of bound and eluted proteins probed
      with anti-Sp17 revealed that AKAP3 bound and precipitated a significant level of
      Sp17 while AKAP4 did not. AKAP4 binds AKAP3 and expression of AKAP3 is reduced in
      AKAP4 knockout sperm, therefore we tested AKAP4 knockout spermatozoa for Sp17 and
      found that there was a reduction in the amount of Sp17 expressed when compared to
      wild type spermatozoa. Co-localization of AKAP3 and Sp17 by immunofluorescence
      was demonstrated along the length of the principal piece of the flagella.
      CONCLUSIONS: As predicted by its N-terminal domain that is 45% identical to the
      human RIIalpha of PKA, Sp17 from spermatozoa binds the RII binding domain of
      AKAP3 along the length of the flagella.

PMID- 15257754
TI  - The Self-Perception and Relationships Tool (S-PRT): a novel approach to the
      measurement of subjective health-related quality of life.
AB  - BACKGROUND: The Self-Perception and Relationships Tool (S-PRT) is intended to be
      a clinically responsive and holistic assessment of patients' experience of
      illness and subjective Health Related Quality of Life (HRQL). METHODS: A
      diversity of patients were involved in two phases of this study. Patient samples
      included individuals involved with renal, cardiology, psychiatric, cancer,
      chronic pelvic pain, and sleep services. In Phase I, five patient focus groups
      generated 128 perceptual rating scales. These scales described important
      characteristics of illness-related experience within six life domains (i.e.,
      Physical, Mental-Emotional, Interpersonal Receptiveness, Interpersonal
      Contribution, Transpersonal Receptiveness and Transpersonal Orientation). Item
      reduction was accomplished using Importance Q-sort and Importance Checklist
      methodologies with 150 patients across the participating services. In Phase II, a
      refined item pool (88 items) was administered along with measures of health
      status (SF-36) and spiritual beliefs (Spiritual Involvements and Beliefs Scale-
      SIBS) to 160 patients, of these 136 patients returned complete response sets.
      RESULTS: Factor analysis of S-PRT results produced a surprisingly clean five
      factor solution (Eigen values> 2.0 explaining 73.5% of the pooled variance).
      Items with weaker or split loadings were removed leaving 36 items to form the
      final S-PRT rating scales; Intrapersonal Well-being (physical, mental & emotional
      items), Interpersonal Receptivity, Interpersonal Contribution, Transpersonal
      Receptivity and Transpersonal Orientation (Eigen values> 5.4 explaining 83.5% of
      the pooled variance). The internal consistency (Cronbach's Alpha) of these scales
      was very high (0.82-0.97). Good convergent correlations (0.40 to 0.67) were
      observed between the S-PRT scales and the Mental Health scales of the SF-36.
      Correlations between the S-PRT Intrapersonal Well-being scale and three of SF-36
      Physical Health scales were moderate (0.30 to 0.46). The criterion-related
      validity of the S-PRT spiritual scales was supported by moderate convergence
      (0.40-0.49) with three SIBS scales. CONCLUSION: Evidence supports the validity of
      the S-PRT as a generally applicable measure of perceived health status and HRQL.
      The test-retest reliability was found to be adequate for most scales, and there
      is some preliminary evidence that the S-PRT is responsive to patient-reported
      changes in determinants of their HRQL. Clinical uses and directions for future
      research are discussed.

PMID- 15257755
TI  - Atypical glandular cells in conventional cervical smears: incidence and follow
      up.
AB  - BACKGROUND: Atypical glandular cells on cervical smears are often associated with
      clinically significant uterine lesions. The frequency and accuracy of AGC-NOS
      (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of
      the gland cell type or the degree of suspicion, and their outcome were
      investigated. METHODS: From January 1, 1990 to December 31, 1999 a total of 261
      patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou
      smear interpretation representing 0.05% of all Pap-smears analyzed at the
      national level. 191 (73.2%) patients had a subsequent histological examination, 8
      samples were not representative by origin and were excluded. RESULTS: Out of 183
      AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven
      precancerous and/or cancerous lesions, 44% being of endocervical and 56% of
      endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the
      patients with subsequent invasive endocervical adenocarcinoma (AC) and 56%
      (28/50) of those patients with invasive endometrial AC were without clinical
      symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of
      age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or
      endometrial AC respectively recorded by the national Morphologic Tumour Registry
      (MTR) were first identified by a cytological AGC-NOS diagnosis. CONCLUSION: Our
      findings emphasize the importance of the cytological AGC-category even in the
      absence of a precise origin or cell type specification. 56% of the AGC-diagnoses
      being associated with significant cancerous or precancerous conditions, a
      complete and careful evaluation is required.

PMID- 15257757
TI  - Myomectomy at time of cesarean delivery: a retrospective cohort study.
AB  - BACKGROUND: Myomectomy at time of cesarean delivery is traditionally discouraged
      because of the risk of hemorrhage. A retrospective cohort study was performed to
      determine whether myomectomy at time of cesarean delivery leads to an increased
      incidence of intrapartum and short-term postpartum complications. METHODS: A
      computer search of medical records from May 1991 to April 2001 identified a total
      of 111 women who underwent myomectomy at time of cesarean delivery and 257 women
      with documented fibroids during the index pregnancy who underwent cesarean
      delivery alone. Charts were reviewed for the following outcome variables: change
      in hematocrit from preoperative to postoperative period, length of operation,
      length of postpartum stay, incidence of postpartum fever, and incidence of
      hemorrhage. Hemorrhage was defined as a change in hematocrit of 10 points or the
      need for intraoperative blood transfusion. RESULTS: The incidence of hemorrhage
      in the study group was 12.6% as compared with 12.8% in the control group (p =
      0.95). There was also no statistically significant increase in the incidence of
      postpartum fever, operating time, and length of postpartum stay. No patient in
      either group required hysterectomy or embolization. Size of fibroid did not
      appear to affect the incidence of hemorrhage. After stratifying the procedures by
      type of fibroid removed, intramural myomectomy was found to be associated with a
      21.2% incidence of hemorrhage compared with 12.8% in the control group, but this
      difference was not statistically significant (p = 0.08). This study had 80% power
      to detect a two-fold increase in the overall incidence of hemorrhage. CONCLUSION:
      In selected patients, myomectomy during cesarean delivery does not appear to
      result in an increased risk of intrapartum or short-term postpartum morbidity.

PMID- 15257756
TI  - Phase I/II study of first-line irinotecan combined with 5-fluorouracil and
      folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer.
AB  - BACKGROUND: This multicentre phase I/II study was designed to determine the
      maximum tolerated dose of irinotecan when combined with 5-fluorouracil and
      folinic acid according to the Mayo Clinic schedule and to evaluate the activity
      of this combination as first-line therapy in patients with advanced colorectal
      cancer. METHODS: Sixty-three patients received irinotecan (250 or 300 mg/m2, 30-
      to 90-minute intravenous infusion on day 1), immediately followed by folinic acid
      (20 mg/m2/day) and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion) days 1 to
      5, every four weeks. RESULTS: Diarrhoea was dose limiting at 300 mg/m2 irinotecan
      in combination with 5-fluorouracil and folinic acid, and this was determined to
      be the maximum tolerated dose. Grade 3-4 neutropenia was the most frequently
      reported toxicity. The recommended dose of irinotecan for the phase II part of
      the study was 250 mg/m2. The response rate for the evaluable patient population
      was 36% (13/36), and 44% (16 patients) had stable disease (including 19% of minor
      response). For the intention-to-treat population, the response rate was 29%
      (14/49) and 35% (17 patients) stable disease (including 14% of minor response).
      The median time to progression was 7.0 months and the median survival was 12.0
      months. Grade 3-4 non-haematological drug-related toxicities included delayed
      diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due
      to septic shock that were possibly or probably treatment-related. CONCLUSIONS:
      This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus
      5-fluorouracil/folinic acid every four weeks showed activity as first-line
      therapy in patients with advanced colorectal cancer. In keeping with other
      published results of studies using bolus 5-fluorouracil combined with irinotecan,
      the use of this regimen is limited by a relatively high rate of grade 3-4
      neutropenia, and the combination of irinotecan and infusional 5-fluorouracil /
      folinic acid should remain the regimen of first choice.

PMID- 15257758
TI  - Resting tachycardia, a warning sign in anorexia nervosa: case report.
AB  - BACKGROUND: Among psychiatric disorders, anorexia nervosa has the highest
      mortality rate. During an exacerbation of this illness, patients frequently
      present with nonspecific symptoms. Upon hospitalization, anorexia nervosa
      patients are often markedly bradycardic, which may be an adaptive response to
      progressive weight loss and negative energy balance. When anorexia nervosa
      patients manifest tachycardia, even heart rates in the 80-90 bpm range, a
      supervening acute illness should be suspected. CASE PRESENTATION: A 52-year old
      woman with longstanding anorexia nervosa was hospitalized due to progressive leg
      pain, weakness, and fatigue accompanied by marked weight loss. On physical
      examination she was cachectic but in no apparent distress. She had fine lanugo
      type hair over her face and arms with an erythematous rash noted on her palms and
      left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate
      was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild
      leukocytosis, and hypoalbuminemia. She was initially treated with enteral
      feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis
      without fever and worsening left leg pain prompted the diagnosis of an indolent
      left lower extremity cellulitis. With antibiotic therapy her heart rate decreased
      to 45 bpm despite minimal restoration of body weight. CONCLUSIONS: Bradycardia is
      a characteristic feature of anorexia nervosa particularly with significant weight
      loss. When anorexia nervosa patients present with nonspecific symptoms, resting
      tachycardia should prompt a search for potentially life-threatening conditions.

PMID- 15257759
TI  - A homotropic two-state model and auto-antagonism.
AB  - BACKGROUND: Bell-shaped and terraced dose-response relations have been observed
      in single ligand application for enzymes, carriers, transporters, G protein
      coupled receptors as well as for other receptive units. It seems that there is
      still a need for new models as analytical tools for such dose-responses,
      especially in the light of expanding di- and multi-merization of the receptive
      units for functionality. RESULTS: Self-inhibition by drugs is analyzed in the
      frame-work of a theoretical homotropic two-state model, HOTSM. The model is a
      cubic reaction scheme based on a combination of conformational isomerization
      between two states within a receptive unit and ternary-complexing of two
      identical agonist molecules with the receptor. Concepts and terms related to self
      inhibition are presented. HOTSM has seven independent parameters. Making a few
      simplifying assumptions narrows its analysis to initially look at four
      parameters. Some conclusions to be drawn are that a first level of spontaneous
      activity is solely determined by an isomerization constant, L. As ligand
      concentration rises, all seven parameters influence a second level of activity.
      At high ligand concentrations, a third level of activity is determined by only
      four of the seven constants, viz. the L constant and three intrinsic efficacy
      related constants, a, b, and d. The third level is given by 1/[1 + 1/(L.a.b.d)].
      The third level may be above, at, or below the first and second levels. When the
      third level is above the first level, dose-responses may be bell-shaped,
      terraced, or reversed bell-shaped while when it is below the first level, dose
      responses can attain forms of bell-shapes, reverse terraces, or reverse bell
      shapes. To exemplify its use, the HOTSM is fitted to experimental dose-responses
      from sources in the literature. Development of the HOTSM is reviewed.
      CONCLUSIONS: The homotropic two-state model, HOTSM, is a novel model for analyses
      of dose-responses at equilibrium that are co-operative or show bell-shapes of
      auto-antagonism.

PMID- 15257760
TI  - Expression profile of genes regulated by activity of the Na-H exchanger NHE1.
AB  - BACKGROUND: In mammalian cells changes in intracellular pH (pHi), which are
      predominantly controlled by activity of plasma membrane ion exchangers, regulate
      a diverse range of normal and pathological cellular processes. How changes in pHi
      affect distinct cellular processes has primarily been determined by evaluating
      protein activities and we know little about how pHi regulates gene expression.
      RESULTS: A global profile of genes regulated in mammalian fibroblasts by
      decreased pHi induced by impaired activity of the plasma membrane Na-H exchanger
      NHE1 was characterized by using cDNA microarrays. Analysis of selected genes by
      quantitative RT-PCR, TaqMan, and immunoblot analyses confirmed results obtained
      from cDNA arrays. Consistent with established roles of pHi and NHE1 activity in
      cell proliferation and oncogenic transformation, grouping regulated genes into
      functional categories and biological pathways indicated a predominant number of
      genes with altered expression were associated with growth factor signaling,
      oncogenesis, and cell cycle progression. CONCLUSION: A comprehensive analysis of
      genes selectively regulated by pHi provides insight on candidate targets that
      might mediate established effects of pHi on a number of normal and pathological
      cell functions.

PMID- 15257762
TI  - Nucleotide diversity of the ZmPox3 maize peroxidase gene: relationships between a
      MITE insertion in exon 2 and variation in forage maize digestibility.
AB  - BACKGROUND: Polymorphisms were investigated within the ZmPox3 maize peroxidase
      gene, possibly involved in lignin biosynthesis because of its colocalization with
      a cluster of QTL related to lignin content and cell wall digestibility. The
      purpose of this study was to identify, on the basis of 37 maize lines chosen for
      their varying degrees of cell wall digestibility and representative of temperate
      regions germplasm, ZmPox3 haplotypes or individual polymorphisms possibly
      associated with digestibility. RESULTS: Numerous haplotypes with high diversity
      were identified. Frequency of nucleotide changes was high with on average one SNP
      every 57 bp. Nucleotide diversity was not equally distributed among site
      categories: the estimated pi was on average eight times higher for silent sites
      than for non-synonymous sites. Numerous sites were in linkage disequilibrium that
      decayed with increasing physical distance. A zmPox3 mutant allele, carrying an
      insertion of a transposable element in the second exon, was found in lines
      derived from the early flint inbred line, F7. This element possesses many
      structural features of miniature inverted-repeat transposable elements (MITE).
      The mutant allele encodes a truncated protein lacking important functional sites.
      An ANOVA performed with a subset of 31 maize lines indicated that the
      transposable element was significantly associated with cell wall digestibility.
      This association was confirmed using an additional set of 25 flint lines related
      to F7. Moreover, RT-PCR experiments revealed a decreased amount of corresponding
      mRNA in plants with the MITE insertion. CONCLUSION: These results showed that
      ZmPox3 could possibly be involved in monolignol polymerisation, and that a
      deficiency in ZmPox3 peroxidase activity seemingly has a negative effect on cell
      wall digestibility. Also, genetic diversity analyses of ZmPox3 indicated that
      this peroxidase could be a relevant target for grass digestibility improvement
      using specific allele introgressions.

PMID- 15257763
TI  - Abstracts of the XXIVth CINP (Collegium Internationale Neuro
      psychopharmacologium) Congress. Paris, France. June 20-24, 2004.

PMID- 15257761
TI  - Novel conserved domains in proteins with predicted roles in eukaryotic cell-cycle
      regulation, decapping and RNA stability.
AB  - BACKGROUND: The emergence of eukaryotes was characterized by the expansion and
      diversification of several ancient RNA-binding domains and the apparent de novo
      innovation of new RNA-binding domains. The identification of these RNA-binding
      domains may throw light on the emergence of eukaryote-specific systems of RNA
      metabolism. RESULTS: Using sensitive sequence profile searches, homology-based
      fold recognition and sequence-structure superpositions, we identified novel,
      divergent versions of the Sm domain in the Scd6p family of proteins. This family
      of Sm-related domains shares certain features of conventional Sm domains, which
      are required for binding RNA, in addition to possessing some unique conserved
      features. We also show that these proteins contain a second previously
      uncharacterized C-terminal domain, termed the FDF domain (after a conserved
      sequence motif in this domain). The FDF domain is also found in the fungal Dcp3p
      like and the animal FLJ22128-like proteins, where it fused to a C-terminal domain
      of the YjeF-N domain family. In addition to the FDF domains, the FLJ22128-like
      proteins contain yet another divergent version of the Sm domain at their extreme
      N-terminus. We show that the YjeF-N domains represent a novel version of the
      Rossmann fold that has acquired a set of catalytic residues and structural
      features that distinguish them from the conventional dehydrogenases. CONCLUSIONS:
      Several lines of contextual information suggest that the Scd6p family and the
      Dcp3p-like proteins are conserved components of the eukaryotic RNA metabolism
      system. We propose that the novel domains reported here, namely the divergent
      versions of the Sm domain and the FDF domain may mediate specific RNA-protein and
      protein-protein interactions in cytoplasmic ribonucleoprotein complexes. More
      specifically, the protein complexes containing Sm-like domains of the Scd6p
      family are predicted to regulate the stability of mRNA encoding proteins involved
      in cell cycle progression and vesicular assembly. The Dcp3p and FLJ22128 proteins
      may localize to the cytoplasmic processing bodies and possibly catalyze a
      specific processing step in the decapping pathway. The explosive diversification
      of Sm domains appears to have played a role in the emergence of several uniquely
      eukaryotic ribonucleoprotein complexes, including those involved in decapping and
      mRNA stability.

PMID- 15257780
TI  - Optimism and pessimism in the context of health: bipolar opposites or separate
      constructs?
AB  - One difficulty plaguing research on dispositional optimism and health is whether
      optimism and pessimism are bipolar opposites or constitute distinct constructs.
      The present study examined the Life Orientation Test to determine whether the two
      factor structure is explained by method bias (due to measurement) or substantive
      differences. The authors compared three measurement models: bipolar, bivariate,
      and method artifact. Optimism and pessimism emerged as distinct constructs due to
      substantive differences. The authors also considered the validity of optimism and
      pessimism, examining their relations with psychological and physical health
      outcomes. Optimism and pessimism were more similar in relation to psychological
      health than to other health-related behavior or physical health outcomes.
      However, a strongly interpretable pattern for the relation of optimism and
      pessimism to the health outcomes did not emerge. Further research may benefit
      from considering optimism and pessimism as bivariate and also should consider the
      conceptual components and behavioral mechanisms specific to each variable.

PMID- 15257781
TI  - The intergenerational transmission of fear of failure.
AB  - The intergenerational transmission of fear of failure was examined in two studies
      with undergraduates and their parents. Parent-undergraduate concordance in fear
      of failure was documented for mothers and fathers, controlling for parents' and
      undergraduate's impression management and self-deceptive enhancement response
      tendencies. Love withdrawal was validated as a mediator of parent-undergraduate
      concordance in fear of failure for mothers but not for fathers. Mothers' and
      fathers' fear of failure was also a positive predictor of undergraduate's
      adoption of performance-avoidance goals in the classroom, and undergraduate's
      fear of failure was shown to mediate this relationship. Fathers' fear of failure
      was also a negative predictor of undergraduate's mastery goal adoption, and this
      relationship was likewise mediated by undergraduate's fear of failure. The
      results are discussed in terms of the reorienting of positive, appetitive
      achievement motivation toward negative, aversive achievement motivation.

PMID- 15257782
TI  - Complicating race: the relationship between prejudice, race, and social class
      categorizations.
AB  - Although racial stereotyping and prejudice research have received considerable
      attention, the important element of social class has been largely excluded from
      social psychological research. Using the Statement Recognition Procedure, two
      experiments investigated social categorization along race and social class
      dimensions, the influence of racial and social class prejudice on these
      categorizations, and differences between White and Black perceivers. Analyses
      conducted at the subtype of race and social class memberships demonstrated
      differing patterns of categorization based on subtype membership. For example,
      lowerclass Black targets were primarily categorized by race, whereas middle-class
      Black targets were primarily categorized by social class. The results demonstrate
      the importance of considering social class membership independent of and in
      conjunction with race. Theoretical and methodological implications regarding the
      study for race and social class categorizations are discussed.

PMID- 15257783
TI  - Group-based self-evaluation outside of the laboratory: effects of global versus
      contextual status.
AB  - An event-contingent diary methodology was used to study the impact of intergroup
      and intragroup factors on self-evaluations in naturally occurring groups.
      Participants reported their contextual group status, group identification, and
      self-evaluations each time they self-categorized as a group member throughout a 1
      week period. Indicators of global group status, interdependence, and permeability
      of group boundaries also were obtained. Multilevel modeling revealed that
      contextual status and global status interacted to predict self-evaluations.
      Contextual status had a stronger relationship with self-evaluations for members
      of global low-status groups than for members of high-status groups. Analyses of
      intragroup factors revealed that greater group interdependence but not
      permeability of group boundaries also was associated with higher self
      evaluations. The effects of both contextual status and group interdependence were
      mediated by group identification.

PMID- 15257784
TI  - Race and information processing in criminal trials: does the defendant's race
      affect how the facts are evaluated?
AB  - Two studies examined whether a criminal defendant's race influences Whites'
      sensitivity to legally relevant information. In Study 1, prosecution case
      strength ratings and guilt likelihood ratings were more sensitive to the strength
      of the defendant's alibi when he was Black than when he was White, if the
      experimental task was designed to elicit low processing motivation. Under high
      motivation, participants were equally sensitive to alibi strength, regardless of
      defendant race. In Study 2, the alibi strength manipulation was replaced with a
      manipulation of the effectiveness of the district attorney's cross-examination.
      As predicted, defense case strength ratings were more sensitive to the strength
      of the prosecutor's cross-examination with a Black defendant than with a White
      defendant-under low motivation. Under high motivation, sensitivity did not depend
      on defendant race. These results suggest that a Black defendant can elicit
      greater sensitivity to legally relevant information than will a White defendant.

PMID- 15257785
TI  - Self-awareness, self-evaluation, and creativity.
AB  - The present research examined when self-evaluation influences creativity. Based
      on objective self-awareness theory, the authors predicted that feeling able to
      improve would buffer against the detrimental effects of self-evaluation on
      creativity. Two experiments manipulated self-evaluation (varying self-awareness,
      Study 1; providing objective performance standards, Study 2) and perceived
      ability to improve potential failure on the creativity task. Self-evaluation
      reduced creativity (generating remote associates, finding unusual uses for a
      knife) in both experiments, but only when people did not expect to improve. When
      people felt able to improve, self-evaluation did not affect creativity.
      Connections between self-motives, creativity, and defensiveness are discussed.

PMID- 15257786
TI  - Emotional intelligence and social interaction.
AB  - Two studies found positive relationships between the ability to manage emotions
      and the quality of social interactions, supporting the predictive and incremental
      validity of an ability measure of emotional intelligence, the Mayer-Salovey
      Caruso Emotional Intelligence Test (MSCEIT). In a sample of 118 American college
      students (Study 1), higher scores on the managing emotions subscale of the MSCEIT
      were positively related to the quality of interactions with friends, evaluated
      separately by participants and two friends. In a diary study of social
      interaction with 103 German college students (Study 2), managing emotions scores
      were positively related to the perceived quality of interactions with opposite
      sex individuals. Scores on this subscale were also positively related to
      perceived success in impression management in social interactions with
      individuals of the opposite sex. In both studies, the main findings remained
      statistically significant after controlling for Big Five personality traits.

PMID- 15257787
TI  - Predicting intergroup bias: the interactive effects of implicit theory and social
      identity.
AB  - This research sought to integrate the implicit theory approach and the social
      identity approach to understanding biases in intergroup judgment. The authors
      hypothesized that a belief in fixed human character would be associated with
      negative bias and prejudice against a maligned group regardless of the
      perceiver's social identity. By contrast, a belief in malleable human character
      would allow the perceiver's social identity to guide intergroup perception, such
      that a common ingroup identity that includes the maligned group would be
      associated with less negative bias and prejudice against the maligned group than
      would an exclusive identity. To test these hypotheses, a correlational study was
      conducted in the context of the Hong Kong 1997 political transition to examine
      Hong Kong Chinese's perceptions of Chinese Mainlanders, and an experimental study
      was conducted in the United States to examine Asian Americans' perception of
      African Americans. Results from both studies supported the authors' predictions.

PMID- 15257788
TI  - Context and cognitions: environmental risk, social influence, and adolescent
      substance use.
AB  - This study examined the cognitions thought to mediate the impact of context on
      adolescent substance use and also the extent to which context moderates the
      relations between these cognitions and use. Risk cognitions and behaviors were
      assessed in a panel of 746 African American adolescents (M age 10.5 at Wave 1,
      12.2 at Wave 2). Results indicated that adolescents living in high-risk
      neighborhoods were more inclined toward substance use and more likely to be using
      at Wave 2. These context effects were mediated by the adolescents' risk
      cognitions: their risk images, willingness to use, and intentions to use. Also,
      context moderated the relation between willingness and use (the relation was
      stronger in high-risk neighborhoods) but it did not moderate the intentions to
      use relation.

PMID- 15257790
TI  - Attachment style and subjective motivations for sex.
AB  - The relation of attachment style to subjective motivations for sex was
      investigated in an Internet survey of 1999 respondents. The relations of
      attachment anxiety and avoidance to overall sexual motivation and to the specific
      motives for emotional closeness, reassurance, self-esteem enhancement, stress
      reduction, partner manipulation, protection from partner's negative affect and
      behavior, power exertion, physical pleasure, nurturing one's partner, and
      procreation were explored. As predicted, attachment anxiety was positively
      related to overall sexual motivation and to all specific motives for sex, with
      the exception of physical pleasure. Avoidance was negatively related to emotional
      closeness and reassurance as goals of sex and positively related to manipulative
      use of sex but minimally related to most other motives. Sexual passion was
      positively related to attachment anxiety and negatively related to avoidance, and
      anxiety was related to the maintenance of passion over time, whereas avoidance
      was related to loss of passion over time.

PMID- 15257789
TI  - Personality and life satisfaction: a facet-level analysis.
AB  - At the global level of the Big Five, Extraversion and Neuroticism are the
      strongest predictors of life satisfaction. However, Extraversion and Neuroticism
      are multifaceted constructs that combine more specific traits. This article
      examined the contribution of facets of Extraversion and Neuroticism to life
      satisfaction in four studies. The depression facet of Neuroticism and the
      positive emotions/cheerfulness facet of Extraversion were the strongest and most
      consistent predictors of life satisfaction. These two facets often accounted for
      more variance in life satisfaction than Neuroticism and Extraversion. The
      findings suggest that measures of depression and positive emotions/cheerfulness
      are necessary and sufficient to predict life satisfaction from personality
      traits. The results also lead to a more refined understanding of the specific
      personality traits that influence life satisfaction: Depression is more important
      than anxiety or anger and a cheerful temperament is more important than being
      active or sociable.

PMID- 15257791
TI  - A randomized, comparative study of two regimens of beta-artemether for the
      treatment of uncomplicated, Plasmodium falciparum malaria, in northern Ghana.
AB  - In Ghana, wide-spread resistance to chloroquine has necessitated the drug's
      replacement as the first-line treatment for malaria, both to increase the
      likelihood of cure and to reduce transmission. To see if beta-artemether could be
      a suitable alternative to chloroquine, 223 adults (aged > or = 15 years) with
      uncomplicated, Plasmodium falciparum malaria were each given a total dose of 480
      mg beta-artemether over 4 or 5 days. The patients were randomly allocated to
      receive an initial, loading dose of 80 or 160 mg, and were checked on days 1, 2,
      3, 4 (or 5), 7 and 14, for fever clearance and any adverse events. Blood samples
      collected on days 0, 4 (or 5), 7 and 14 were smeared so that levels of
      parasitaemia could be evaluated. Haemoglobin concentrations on days 0 and 14 were
      also determined. In terms of the clinical cure 'rates' estimated in the intention
      to-treat analysis (92.5% v. 97.4%) and the evaluability analysis (98.9% v. 100%),
      and of the frequency of parasitological cure by day 14 (97.0% v. 96.5%), the
      patients given an initial dose of 80 mg were similar to those given 160 mg as the
      loading dose. The regimen with the 160-mg loading dose appears as safe and as
      effective as the regimen with an initial dose of 80 mg. Since the regimen with
      the higher loading dose is shorter and involves fewer treatments than the other
      regimen, it would probably be associated with better compliance.

PMID- 15257792
TI  - Low-dose quinine is effective in the treatment of chloroquine-resistant
      Plasmodium falciparum malaria in eastern Sudan.
AB  - In November-December 2002, 98 patients presented at the Elhara Eloula health
      centre, in the New Halfa area of eastern Sudan, with Plasmodium falciparum
      malaria that had failed to respond to chloroquine treatment. After informed
      consent was obtained, 93 of these patients were randomly allocated to one of
      three regimens for quinine treatment, being given the drug, orally and sometimes
      intravenously, for 7 days, at doses of 10 mg/kg thrice daily (32 patients), 10
      mg/kg twice daily (31 patients) or 15 mg/kg once daily (30 patients). All the
      patients were followed daily until day 7 and then weekly until day 28. There was
      no significant difference in the parasite-clearance times observed in the three
      groups. Parasitaemias re-occurred by day 28 in 12 patients: two (6.3%) of the
      patients treated thrice daily, five (16.1%) of those treated twice daily, and
      five (16.7%) of those treated once daily (P > 0.05). Genotyping indicated that in
      nine of these 12 patients the parasitaemias that developed post-treatment
      represented true recrudescences and not re-infections. In the treatment of
      chloroquine-resistant, P. falciparum malaria in Sudan, once-daily treatment with
      quinine, in a relatively low daily dose (15 mg/kg. day), appears as effective as
      the thrice-daily treatment (at 30 mg/kg. day) often recommended.

PMID- 15257793
TI  - Efficacy of chloroquine in the treatment of Plasmodium vivax malaria in Turkey.
AB  - In most regions of the world, chloroquine (CQ) has been the standard treatment
      for Plasmodium vivax malaria for more than 40 years. Recently, however, CQ
      resistant P. vivax has been reported from Oceania, several parts of Asia, and
      South America. The therapeutic efficacy of CQ in the treatment of acute, P. vivax
      malaria has now been assessed in two areas of the Turkish province of Sanliurfa:
      the towns of Karacadag and Sekerli. On admission and on days 2, 3, 7, 14, 21, and
      28, all 112 patients investigated were examined clinically and blood samples were
      collected and smeared. Treatment consisted of 10 mg CQ/kg on day 0, the same dose
      on day 1, and 5 mg CQ/mg on day 2, each dose being supervised. Worryingly, 14.7%
      of the patients from Karacadag and 10.3% of those from Sekerli showed apparent
      treatment failure between days 3 and 28. In Sanliurfa province, in south-eastern
      Turkey, there therefore seems to be a high risk of therapeutic failure in
      patients given CQ to cure P. vivax malaria, probably because of CQ resistance.

PMID- 15257794
TI  - A prospective study evaluating the efficacy of a single, 45-mg dose of
      primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum
      malaria in Mumbai, India.
AB  - The efficacy of a single dose of 45 mg primaquine, as a gametocytocidal agent,
      was assessed in Mumbai, India, among adults with uncomplicated or severe
      Plasmodium falciparum malaria. All the patients investigated had been found
      gametocytaemic, with at least 56 gametocytes/microl blood, within the first 72 h
      of their illness. Those with uncomplicated malaria, like those with severe
      malaria, were randomized to receive or not receive primaquine. All the patients
      were followed up for 29 days post-admission, for gametocytaemia and gametocyte
      viability (as determined by exflagellation). Among those with uncomplicated
      malaria, six (27.3%) of the 22 who did not receive primaquine but only one (4.2%)
      of the 24 who did receive the drug, on day 4, remained gametocytaemic on day 29
      (P < 0.05). Similarly, seven (31.8%) of the 22 severe cases who did not receive
      primaquine but only two (9.5%) of the 21 severe cases who received the drug, on
      day 8, were found gametocytaemic on day 15 (P < 0.05). While the single, 45-mg
      dose of primaquine recommended by the World Health Organization was effective in
      clearing gametocytes from the blood of > 90% of the present cases of malaria, >
      4% of the patients with uncomplicated malaria and > 9% of those with the severe
      disease continued to harbour gametocytes in their peripheral blood 29 and 15 days
      after taking the primaquine, respectively.

PMID- 15257795
TI  - Malarial morbidity in tribal communities living in the forest and plain ecotypes
      of Orissa, India.
AB  - A detailed epidemiological study of malarial morbidity was carried out in 13
      'tribal' villages in the forest or plain ecotypes of Sundargarh district, Orissa,
      India. Longitudinal and cross-sectional, parasitological surveys were conducted
      in all the villages, to determine the incidence of malaria and the prevalence of
      malarial infection. The annual numbers of malaria cases/1000 were much higher in
      the forest (347.9) than on the plain (61.0). In the forest clinical malaria
      occurred more frequently in children than in adults but on the plain all age
      groups were equally affected. In cross-sectional surveys, 14.1% of the subjects
      from the forest but only 2.8% of those from the plain were found smear-positive
      for malarial infection. The prevalences of infection in the forest area were
      highest in the young children (aged 1-5 years) and gradually declined with
      increasing age. The highest incidence of Plasmodium falciparum malaria (0.90
      episode/person-year) was also recorded in the subjects from the forest who were
      aged 1-5 years. In the forest and plain communities surveyed, 78.5%-81.5% and
      36.0%-52.0% of the children aged 2-9 years had detectable splenomegaly,
      respectively, indicating that the forest was hyper-endemic and the plain meso
      endemic for malaria. Malaria is clearly a major problem among the tribal
      communities of Sundargarh, causing great morbidity and, consequently,
      considerable economic losses.

PMID- 15257796
TI  - Quantification of Plasmodium malariae infection in mosquito vectors.
AB  - Plasmodium malariae occurs in various tropical regions throughout the world and
      causes low, yet significant, levels of morbidity in human populations. One means
      of studying the ecology and frequency of this parasite is by measuring sporozoite
      loads in the salivary glands of infected mosquitoes. An effective, species
      specific test that can be used to detect the presence of sporozoites in
      mosquitoes is the circumsporozoite ELISA. The aim of the present study was to
      standardize the circumsporozoite ELISA for P.malariae, by setting quantification
      parameters using, as antigen, either a synthetic peptide or extracts of whole
      sporozoites. The standard quantification curves produced indicated that the assay
      had a lower threshold of sensitivity of 250 sporozoites in a 50-microl sample,
      equivalent to about 1250 sporozoites in a mosquito.

PMID- 15257797
TI  - Cystic echinococcosis of livestock and humans in central Sudan.
AB  - New information was collected on cystic echinococcosis in livestock (camels,
      cattle and sheep) and humans in the central region of Sudan. The livestock data
      were collected in abattoir-based surveys in the towns of Omdurman, Tamboul and
      Wad Madani, between 1998 and 2001, and covered a total of 8205 animals. The
      highest prevalence of infection was found in the camels (44.6% of 242 infected),
      followed by the sheep (6.9% of 5595) and cattle (3.0% of 2368). Records were made
      of the sizes of the 1320 hydatid cysts detected in the livestock (907 in sheep,
      71 in cattle, and 342 in camels), whether or not each cyst was fertile, and where
      it occurred in the body of the host. Cysts collected from cattle and camels where
      much more likely to be fertile (22% and 24%, respectively) than those from sheep
      (1%). Camels and cattle therefore appear to be the principal intermediate hosts
      for Echinococcus granulosus in central Sudan, whereas sheep apparently play a
      marginal role in transmission. In 2002, as a preliminary assessment of the public
      health impact of the disease, 300 residents of a rural village 60 km west of Wad
      Madani were surveyed using a portable ultrasound scanner. Only one (0.33%) of the
      villagers investigated was found infected. The implications of these finding are
      discussed in terms of the various strains of E. granulosus and the role of each
      in human disease.

PMID- 15257798
TI  - Cystic echinococcosis in the Berber of the Mid Atlas mountains, Morocco: new
      insights into the natural history of the disease in humans.
AB  - Precise knowledge of the natural history of cystic echinococcosis (CE) in humans
      remains somewhat arcane. The aim of the present study was to determine whether
      aspects of the natural history of established human infection with Echinococcus
      granulosus could be investigated by using a cross-sectional approach, in a
      community where CE was endemic. A mass ultrasound-screening survey, coupled with
      a questionnaire to record all previous surgical histories related to CE, was
      carried out amongst the primarily transhumant Berber people of the Mid Atlas
      mountains in Morocco. During two periods of intensive screening, of 10 days in
      May 2000 and 11 days in May 2001, 11,612 people, representing > 98% of the local
      population, were checked. One hundred and twenty six (1.1%) of the subjects--75
      (59.5%) of the 6864 females investigated and 51 (40.5%) of the 4748 males--were
      found ultrasound-positive for CE. Overall, 14.1% of the CE cases detected were
      children aged 1-15 years (who made up 44% of the study population). Most (77.4%)
      of the ultrasound-positive subjects investigated were also found seropositive for
      CE. The frequency of a past history of surgery for CE increased with subject age
      (P = 0.024), 125 (1.1%) of the subjects being recorded as having had such
      surgery. The frequency of surgery for pulmonary CE was relatively constant in all
      age-groups, indicating that infection can occur at any time. The frequency of
      abdominal CE increased with age (R2 = 0.8102). Assuming that the incidence of
      infection remains fairly constant over time and that the longer a person spends
      in this endemic area the more likely it is that he or she will develop CE, then a
      progression from active through transitional to inactive CE should occur. The
      cysts observed by ultrasound in the present study were categorized, as type 1, 2,
      3, 4 or 5, according to the new, standardized, ultrasound classification of CE
      developed by the World Health Organization (WHO). There was a clear exponential
      decline in the frequency of the various cyst types, from type 1 (the most
      frequent) to type 5 (the rarest). This decline validates the assumptions made,
      about the natural history of established CE, by those who developed the WHO's
      classification. The classification should therefore be invaluable to surgeons and
      clinicians, when they have to consider treatment options for patients with the
      various types of CE, and to policy makers trying to establish the economic costs
      of treating CE in endemic settings.

PMID- 15257799
TI  - Efficacy of artesunate in the treatment of urinary schistosomiasis, in an endemic
      community in Nigeria.
AB  - The efficacy and tolerability of oral artesunate for the treatment of urinary
      schistosomiasis was assessed among schoolchildren aged 5-18 years in Adim
      community, Nigeria. Overall, 500 children, randomly selected from those attending
      the Presbyterian primary school, were each invited to provide two consecutive
      urine samples. Using standard parasitological procedures, Schistosoma haematobium
      ova were found in the samples from 145 (29.0%) of the subjects. Most (87) of the
      infected subjects were then treated orally with artesunate, using two doses, each
      of 6 mg/kg, given 2 weeks apart. When the treated children were re-examined 4
      weeks after the second dose of artesunate, 61 (70.1%) appeared egg-negative and
      were therefore considered cured. Post-treatment, the geometric mean egg count
      (GMEC) for the treated subjects who were not cured was significantly lower than
      the pre-treatment GMEC for all the treated subjects, with log10[(eggs/10 ml
      urine) + 1] values of 0.9 v. 1.75 (t = 4.45; P < 0.05). The cure 'rate' for the
      subjects aged > or = 10 years was slightly higher than that among the younger
      subjects. It was lowest for the heavier subjects (70% for those weighing 41-50
      kg) and highest (79%) for the subjects who weighed 31-40 kg. The artesunate was
      well tolerated. This observation of a therapeutic effect of artesunate against S.
      haematobium in Nigeria confirms recent observations from Senegal. In the Adim
      community at least, it would be more cost-effective to treat urinary
      schistosomiasis with artesunate than with praziquantel. The wide-spread use of
      artesunate against schistosomiasis has to be considered carefully, however, if it
      is not to compromise the efficacy of the drug as an antimalarial, by increasing
      the risk of resistance developing in local Plasmodium.

PMID- 15257800
TI  - Vector competence, for Wuchereria bancrofti, of the Anopheles populations in the
      Bongo district of Ghana.
AB  - The ability of vector mosquitoes to transmit the microfilariae (mff) of
      Wuchereria bancrofti, especially when the levels of microfilaraemia in the humans
      on which the mosquitoes are feeding are very low, is very important for
      understanding the transmission dynamics of lymphatic filariasis. Data on the
      correlation between vector competence and the microfilarial load in the human
      host are also relevant to those trying to improve transmission models for this
      disease. The majority of the relevant studies have involved culicine rather than
      anopheline vectors. The competence of populations of Anopheles mosquitoes to
      transmit W. bancrofti in a district in the Upper East region of Ghana has now
      been investigated. The wild mosquitoes that fed on 20 volunteers under natural
      conditions were collected hourly during the night, from 21.00 hours on one day to
      06.00 hours on the next. Overall, 1348 fed female mosquitoes--665 Anopheles, 662
      Culex and 21 Aedes--were collected. Approximately 50% of the mosquitoes caught
      were killed immediately post-collection and dissected so that the number of W.
      bancrofti mff each had ingested could be counted. The remaining mosquitoes where
      dissected when they died (if this was within 12 days of collection) or when they
      were killed on day 12 post-collection. With the exception of one Culex mosquito
      that harboured one microfilaria, none of the Culex and Aedes mosquitoes were
      found infected with W. bancrofti. All of the other mosquitoes found infected were
      An. gambiae s.l. or An. funestus. When fingerprick samples of blood, collected
      hourly from the volunteers during the mosquito infection, were used to estimate
      the microfilaraemias in the blood on which these mosquitoes had fed,
      microfilarial uptake and the number of developing larvae were found to vary
      considerably even when the microfilaraemias in the bloodmeal source were similar.
      The results of a regression analysis on the pooled data for the Anopheles
      mosquitoes indicated the process of limitation, although larger samples need to
      be investigated to determine whether this process occurs only in An. gambiae s.l.
      or An. funestus or in both of these taxa.

PMID- 15257801
TI  - The cytotaxonomy and morphotaxonomy of Simulium mengense (Diptera: Simuliidae).
AB  - Human onchocerciasis is hyper-endemic in south-western Cameroon and the island of
      Bioko. The vector on the island is the endemic 'Bioko' form of Simulium yahense.
      On the mainland, S. damnosum s.s., S. squamosum and S. mengense are recorded
      around Mount Cameroon but their contribution to transmission in the area is
      unclear. As elimination of onchocerciasis, through vector eradication, is a
      possibility on the island, it is important to be able to identify vector flies
      which might migrate to Bioko from the mainland. The morphologies of S. damnosum
      s.s. and S. squamosum are already well known. New cytotaxonomic and
      morphotaxonomic descriptions of S. mengense, a species which is less well known,
      are presented. Simulium mengense can be distinguished from the other cytospecies
      in the area by the presence of tufts of hair-like setae on the larval thorax, the
      presence of hairs on the subcostal vein of the adult female, and by the scutal
      pattern of the adult male. Although Vajime and Dunbar described seven fixed
      inversions in S. mengense, in 1977, nine were observed in the present study. Of
      the nine, three were the same as Vajime and Dunbar's but the other six were
      either missed or misinterpreted by them.

PMID- 15257802
TI  - Preliminary report of the evaluation of the gametocytocidal action of bulaquine,
      in adult patients with acute, Plasmodium falciparum malaria.

PMID- 15257803
TI  - American trypanosomiasis in central Mexico: Trypanosoma cruzi infection in
      triatomine bugs and mammals from the municipality of Jiutepec in the state of
      Morelos.

PMID- 15257804
TI  - Ivermectin improves the skin condition and self-esteem of females with
      onchocerciasis: a report of two cases.

PMID- 15257805
TI  - Mating competitiveness of irradiated Glossina austeni tsetse flies.

PMID- 15257806
TI  - Replacement of native freshwater snails by the exotic Physa acuta (Gastropoda:
      Physidae) in southern Mozambique; a possible control mechanism for
      schistosomiasis.

PMID- 15257809
TI  - Development of children born after IVF and ICSI.
AB  - Follow-up studies of pregnancies as well as children born following assisted
      reproductive technologies are of utmost interest to provide a reliable basis for
      patient counselling. Especially in recent years, studies of high quality have
      been performed and published, showing some slight but significantly increased
      risk for pregnancy complications as well as major malformation rate following IVF
      and intracytoplasmic sperm injection (ICSI). The health status and subsequent
      development of children born seems to be comparable to those after spontaneous
      conception up to the age of 5 years. The study of Bonduelle and co-workers,
      published in this issue of Reproductive Biomedicine Online, contributes further
      to the follow-up information available for children born after ICSI. However,
      there are some limitations for all these follow-up studies, which have to be
      taken into account, when interpreting results. These are discussed in this
      commentary.

PMID- 15257810
TI  - A zygote is not an embryo: ethical and legal considerations.
AB  - In spite of several past attempts at defining the point at which conception can
      be considered completed, resulting in the formation of an embryo, the existing
      definitions are still contradictory. In the absence of clear terminology, the
      application of laws aimed at the protection of early human life may have
      inadequate consequences for the efficacy of the current techniques of human
      infertility treatment. In this paper biological arguments are revisited,
      suggesting that the only point at which a clear demarcation line between what is
      and what is still not an embryo can be drawn is the moment of nuclear syngamy at
      the outset of the first cleavage division. The term 'zygote' is suggested to
      denote entities composed of spermatozoon and oocyte components before nuclear
      syngamy. It is suggested that the current embryo protection laws should not
      concern the zygote stage: at this stage, the main features that are said, in
      documents issued by different ethical and legal authorities, to characterize the
      early human embryo, namely the inseparable union of the male and female
      contribution, cell division and an autonomous control over cell division, are
      still not present. This reasoning strictly applies to embryos of biparental
      (paternal and maternal contribution) origin and cannot be extrapolated to embryos
      created by cell nuclear transfer (cloning). The application of embryo protection
      laws from the nuclear syngamy stage onwards can regulate embryo and embryo
      derived stem cell research while still preserving the current high standard and
      efficacy of infertility treatment, which is of immediate interest to millions of
      infertile couples throughout the world.

PMID- 15257811
TI  - 17 alpha-hydroxyprogesterone caproate versus intravaginal progesterone in IVF
      embryo transfer cycles: a prospective randomized study.
AB  - One of the main issues in the management of IVF and embryo transfer techniques is
      to ensure adequate concentrations of progesterone. The aim of this prospective,
      randomized study was to compare the effectiveness of 17 alpha 
      hydroxyprogesterone caproate (17-HPC) administered intramuscularly and intra
      vaginal progesterone in gel in luteal phase support in patients undergoing IVF
      embryo transfer cycles. A total of 320 patients were randomly treated with either
      17-HPC (341 mg i. m. every 3 days) or progesterone vaginal gel (90 mg daily). The
      inclusion criteria were the use of gonadotrophin-releasing hormone down
      regulation and age <40 years. The outcome of IVF in both study groups was
      evaluated for implantation rate, biochemical pregnancy, clinical pregnancy,
      miscarriage, and ongoing pregnancy rate. The results of this study showed that 17
      HPC conferred more benefit to IVF-embryo transfer cycles compared with intra
      vaginal progesterone, as demonstrated by the results of most of the main outcome
      parameters considered. The data showed that 17-HPC administered every 3 days
      appears to be more effective in providing luteal support in comparison to intra
      vaginal progesterone.

PMID- 15257812
TI  - Luteal phase defects following agonist-triggered ovulation: a patient-dependent
      response.
AB  - The luteal phase (LP) of patients receiving triptorelin 0.1 mg to trigger
      ovulation was studied. Patients not pregnant in the first cycle with 0.1 mg were
      randomized into different groups for a second cycle: 0.1 mg again for patients
      who experienced a normal LP (group 1); patients affected with LP disorders were
      randomized into the following groups: 0.1 mg again (group 2); increasing dosage
      of triptorelin 0.5 mg once (group 3) or 0.1 mg three times (group 4); luteal
      support either with oral micronized progesterone (group 5) or human chorionic
      gonadotrophin (HCG) 1500 IU (group 6). Ovulation occurred in all cycles, but an
      inadequate LP was observed in 34.4% of the non-conceptional cycles. Patients
      demonstrating a normal LP as well as those affected with luteal disorders in
      their first cycle showed the same luteal pattern in their consecutive cycles
      triggered in the same way. In defective LP patients, increasing or repeating
      triptorelin doses did not restore the luteal phase or the pregnancy rate, both
      returning closer to normal after luteal support. Defective LP observed after
      agonist-triggered ovulation do not occur at random; therefore this patient
      dependent response may be related to the personal characteristics of each
      patient's pre-ovulatory physiological surge profile.

PMID- 15257813
TI  - Genetic contributions to glucose intolerance in polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) are predisposed to develop impaired
      glucose tolerance and type-2 diabetes mellitus. Genetic factors appear to
      contribute to the insulin resistance that is characteristic of PCOS as well as to
      the failure of the pancreatic beta-cell to compensate adequately for this insulin
      resistance. The cumulative results of studies examining the genetic contribution
      to both the reproductive and metabolic phenotypes of PCOS are consistent with
      PCOS as a complex, polygenic disorder. This article reviews the background and
      recent studies examining the genetic contributions to glucose intolerance in
      PCOS.

PMID- 15257815
TI  - Surgical treatment of polycystic ovary syndrome associated with infertility.
AB  - Laparoscopic ovarian drilling is a relatively simple procedure performed by
      minimal access and usually on an outpatient basis. It provides an alternative
      treatment option for polycystic ovary syndrome (PCOS) patients anovulatory to
      clomiphene citrate. The mechanism of action of laparoscopic ovarian drilling is
      unclear; its beneficial effect is apparently due to destruction of the androgen
      producing stroma. The procedure appears to have little or no effect on insulin
      sensitivity and lipoprotein profile. The majority (56-94%) of PCOS patients who
      are clomiphene citrate resistant ovulate after drilling, and at least half of
      them go on to achieve a pregnancy. Predictive factors for pregnancy are younger
      age and lower body mass index. The endocrine changes resulting from ovarian
      drilling last for an extended period of time. Exogenous gonadotrophin treatment
      and laparoscopic ovarian drilling appear to yield comparable ovulation and
      pregnancy rates; however, multiple pregnancy is rare with drilling. There are
      several complications associated with the procedure, including post-operative
      periadnexal adhesion formation. Alternative treatment options, including
      lifestyle modification (diet and exercise) and metformin, may well reduce the
      need for ovarian drilling in well-selected cases. Progress in understanding of
      this complex syndrome and effective new treatments will further diminish the need
      for surgery.

PMID- 15257818
TI  - Single sperm cryopreservation on cryoloops: an alternative to hamster zona for
      freezing individual spermatozoa.
AB  - Methodology enabling cryopreservation of individual spermatozoa in extreme cases
      of oligozoospermia would tremendously benefit patients. This study explores the
      use of a nylon loop for cryopreservation of small quantities of spermatozoa, and
      also describes a novel technique for freezing individual spermatozoa with this
      cryoloop. Experiments were conducted to compare sperm recovery and viability
      after cryopreservation in conventional vials versus on the cryoloops. Discarded
      human sperm specimens with varying parameters were utilized. The study also
      examines two different glycerolbased cryoprotectants, with and without test yolk
      buffer. For single sperm cryopreservation, 5-10 spermatozoa were selected and
      loaded onto cryoloops with the aid of a microscope and micromanipulation
      equipment. Sperm function testing was performed on both human and bovine
      spermatozoa frozen on cryoloops. Microquantities of spermatozoa frozen on
      cryoloops exhibited overall motility and viability parameters similar to control
      samples frozen in cryovials. Individually selected spermatozoa cryopreserved on
      loops were easily recovered and post-thaw motility was generally good. Sperm
      function testing demonstrated that both human and bovine spermatozoa
      cryopreserved on loops were able to undergo sperm head decondensation when
      injected into oocytes. Cryoloops may be an excellent alternative to hamster zonae
      for cryopreserving small numbers of human spermatozoa.

PMID- 15257817
TI  - Improving results with assisted reproductive technologies: individualized patient
      tailored strategies for ovulation induction.
AB  - Infertility treatment should be made as efficacious as possible while being
      simple for patients. Although the treatment paradigm may be, at times, complex,
      patients deserve pure products that simplify protocol implementation while
      providing reliable outcomes. The more the treatment experience is simplified and
      improved, the more patients will benefit from the technology.

PMID- 15257819
TI  - Cytoplasmic dysmorphisms in metaphase II chimpanzee oocytes.
AB  - Prior to fertilization by intracytoplasmic sperm injection (ICSI), cytoplasmic
      organization was evaluated in metaphase II chimpanzee oocytes obtained from
      stimulated ovaries. The findings demonstrate a high frequency of anomalies that
      are remarkably similar to the types of cytoplasmic dysmorphisms reported for
      human oocytes used in IVF. Similar to the human, the occurrence of these
      anomalies was oocyte- and animal-specific and associated with reduced competence
      as indicated by embryo development in vitro to the blastocyst stage.

PMID- 15257821
TI  - Enhanced effect of glycyl-L-glutamine on mouse preimplantation embryos in vitro.
AB  - A comparison of the effects of replacing L -glutamine with either glycyl-L
      glutamine or alanyl-L-glutamine in a KSOM-type medium on the development of mouse
      preimplantation embryos in vitro has been made. Alanyl-L-glutamine has no
      significant effect on the rates of blastocyst formation, onset or completion of
      hatching, and on the numbers of inner cell mass and trophectoderm cells that
      develop. Glycyl-L-glutamine has no effect on the rate of blastocyst formation; it
      stimulates slightly the onset of hatching, but significantly increases the
      numbers of inner cell mass and trophectoderm cells that develop. Embryo transfer
      experiments comparing media containing either glutamine or glycyl-L-glutamine
      have not produced any gross abnormal fetal development. Recently, alanyl-L
      glutamine has been used to replace glutamine in media for the culture of human
      preimplantation embryos. The results in this paper suggest that glycyl-L
      glutamine may be a better choice of dipeptide.

PMID- 15257823
TI  - Discrepancies between the effects of glutamine in cultures of preimplantation
      mouse embryos.
AB  - A review of the literature shows divergent differences between laboratories of
      the effects of glutamine in mouse preimplantation embryo culture media. One
      laboratory reported several cases of exencephaly, which was attributed to ammonia
      produced by the breakdown of glutamine. Two other laboratories have found no such
      effects. It is suggested, but not proved, that the differences in results may
      have a genetic basis. Further, it is argued that studies on the toxicological
      actions of exogenous ammonium chloride on preimplantation development provide a
      biased model of the effects of glutamine as used in embryo culture protocols. The
      finding that ammonium can also cause exencephaly thus fosters undue concern about
      the teratological effects of glutamine.

PMID- 15257824
TI  - Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a
      potentially valuable indicator of 'embryo competency' and IVF outcome.
AB  - A retrospective cohort study was conducted on 201 women aged 28-44 years, each of
      whom underwent one cycle of IVF-embryo transfer with fresh, intracytoplasmic
      sperm injection (ICSI)-derived 7- to 10-cell embryos, transferred 72 h after
      oocyte retrieval. Samples of media surrounding separately cultured embryos were
      collected 46 h post-ICSI and stored for subsequent specific enzyme-linked
      immunosorbent assay. A total of 594 embryos (from own or donor oocytes) were
      transferred to 201 women. Group A comprised 159 recipients under 39 years and
      group B compromised 42 recipients aged 39-44 years. Groups A-1 and B-1 recipients
      had at least one embryo that tested above the geometric mean for soluble human
      leukocyte antigen-G (sHLA-G) ('positive expression') transferred. In groups A-2
      and B-2, all embryos transferred expressed sHLA-G below the geometric mean
      ('negative expression'). In group A-1, 72/101 women (71%) achieved ultrasound
      confirmed (clinical), viable (cardiac activity observed) pregnancies. The
      implantation rate per embryo (IR) was 38%. In group A-2, 13/58 (22%) achieved
      viable clinical pregnancies. The IR was 9%. In group B-1, the viable clinical
      pregnancy rate was 52% (15/29) and the IR was 25% compared with a viable clinical
      pregnancy rate of 15% (2/13) and an IR of 5% in group B-2. The results of this
      study suggest that by selecting specific embryos for transfer based on their
      individual sHLA-G expression, pregnancy and implantation rates can be maximized
      while the number of embryos transferred can be reduced, thereby minimizing the
      incidence of high-order multiple pregnancies.

PMID- 15257825
TI  - Effect of PGD on implantation and ongoing pregnancy rates in cases with
      predominantly macrocephalic spermatozoa.
AB  - Although its occurrence is rare, the presence of large headed or macrocephalic
      spermatozoa and increased chromosomal abnormality has recently been reported by
      several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was
      performed with samples containing macrocephalic spermatozoa, lower fertilization
      and implantation rates result in poor clinical outcome. In order to evaluate the
      impact of preimplantation genetic diagnosis (PGD) on implantation and ongoing
      pregnancy rates in these couples, the results of 23 PGD cycles were compared with
      non-PGD cycles (n = 60) as well as cycles with absolute teratozoospermia (having
      zero normal morphology) with (n = 14) or without PGD (n = 66). Out of 82 embryos
      biopsied in the macrocephalic sperm group, abnormalities were detected in 46.4%
      of the embryos analysed. Most of the abnormalities were trisomies (37.0%) and
      complex aneuploidies (51.9%). A 33.3% pregnancy rate was achieved by selectively
      transferring euploid embryos after PGD with the statistically higher implantation
      rate of 25.0% compared with non-PGD cycles (IR: 12.3%, P < 0.01). Moreover, only
      one missed abortion (14.3%) was observed in the PGD group, whereas seven of the
      15 pregnancies resulted in abortion in the non-PGD group (46.7%). Preliminary
      results indicate that patients should be counselled for increased chromosomal
      abnormality and a possible beneficial effect of eliminating chromosomally
      abnormal embryos with PGD on a bortion rates.

PMID- 15257827
TI  - Clinical value of endometrial pinopodes detection in artificial donation cycles.
AB  - The aim of the study was to investigate the clinical value of pinopode detection
      in women with a history of multiple implantation failures after participation in
      assisted reproduction programmes. Forty-six women with primary infertility, three
      or more previous implantation failures in assisted reproduction programmes and
      indication for the use of donated oocytes underwent a mock cycle of endometrial
      preparation, based on a standard protocol. Endometrial samples were taken on days
      6 and 8 of progesterone administration, and were examined under scanning electron
      microscope for detection and evaluation of pinopodes. The most receptive
      endometrial day (the day on which fully developed pinopodes can be demonstrated)
      was determined for each woman. In 73.91%, a new modified transfer cycle was
      suggested and applied by altering the timing between IVF and progesterone
      commencement days; 76.47% achieved a clinical pregnancy within two attempts and
      67.64% delivered a healthy baby. Among women with no indication for modification
      of their transfer cycle, only 33.33% achieved a pregnancy and 25% delivered a
      healthy baby. The difference in the outcomes between transfer cycles with and
      without modification was significant. In conclusion, detection of pinopodes in
      women with multiple implantation failures can be of great clinical value.

PMID- 15257828
TI  - Medical follow-up study of 5-year-old ICSI children.
AB  - Children born after intracytoplasmic sperm injection (ICSI) are still a matter of
      concern. The purposes of the present study were to investigate the physical
      outcome in 5-year-old children born after ICSI and compare them with children
      born after spontaneous conception. Three hundred singleton children from Belgium,
      Sweden and the USA, born after ICSI, were matched by maternal age, child age and
      gender. In one centre, matching was also performed for maternal education. The
      main end-point was growth. Secondary end-points were general health, e.g. common
      diseases, chronic illnesses, surgical interventions and physical/neurological
      examinations. Standard deviation scores assessed growth. Growth assessed as
      stature at follow-up was similar in the two groups, despite a higher rate of
      preterm birth and low birth weight in the ICSI children. Common diseases and
      chronic illnesses occurred at similar rates in both groups. More ICSI children
      underwent surgical interventions and required other therapy e. g. physiotherapy
      and dietary therapy. Physical/neurological examinations revealed few
      abnormalities in either group. In conclusion, infertility treatment by ICSI does
      not adversely affect growth during childhood. The children's general health seems
      satisfactory.

PMID- 15257830
TI  - Percutaneous aspiration biopsy using an intravenous catheter for testicular sperm
      retrieval in patients with obstructive azoospermia.
AB  - Testicular needle aspiration has been proposed as a simple alternative to open
      biopsy for the diagnosis and treatment of azoospermia. This study describes a new
      modification of needle aspiration biopsy using an ordinary intravenous catheter
      to retrieve testicular spermatozoa from patients with obstructive azoospermia,
      and compares it to the classical fine-needle aspiration (FNA) method. The study
      included 86 consecutive patients with obstructive azoospermia. Thirty-one
      patients underwent FNA using butterfly needles (G21 or G23) and a 20 ml syringe.
      For the remaining 55 patients, an i.v. catheter (G14 or G16) was used instead of
      the butterfly needle. When testicular tissue was seen in the aspirate, the
      catheter was clamped and removed from the testis. If, after a maximum of three
      punctures, insufficient spermatozoa were retrieved, an open biopsy was carried
      out. Successful sperm retrieval was achieved in 54 out of 55 patients (98.1%)
      using an i.v. catheter, compared with 16 out of 31 patients (51.6%) using FNA (P
      < 0.05). Enough aspirated tissue was obtained for cryopreservation of spermatozoa
      in all 54 patients using the i.v. catheter, compared with 6/16 (37.5%) of the
      patients undergoing classical FNA. No significant complications were reported. In
      conclusion, the use of an i.v. catheter for testicular aspiration biopsy
      significantly improved sperm retrieval compared with FNA in obstructive
      azoospermia, and allowed for cryopreservation of excess tissue. The procedure is
      simple and inexpensive, however regular follow up and testing of possible adverse
      consequences of this method is indicated to establish its safety.

PMID- 15257831
TI  - Abstracts from the 9th Annual CyberTherapy Conference: Interactive Media in
      Training and Therapeutic Interventions. January 10-12, 2004, San Diego,
      California, USA.

PMID- 15257832
TI  - The online disinhibition effect.
AB  - While online, some people self-disclose or act out more frequently or intensely
      than they would in person. This article explores six factors that interact with
      each other in creating this online disinhibition effect: dissociative anonymity,
      invisibility, asynchronicity, solipsistic introjection, dissociative imagination,
      and minimization of authority. Personality variables also will influence the
      extent of this disinhibition. Rather than thinking of disinhibition as the
      revealing of an underlying "true self," we can conceptualize it as a shift to a
      constellation within self-structure, involving clusters of affect and cognition
      that differ from the in-person constellation.

PMID- 15257833
TI  - Training with computer-supported motor imagery in post-stroke rehabilitation.
AB  - Converging lines of evidence suggest that motor imagery (the mental simulation of
      a motor act within working memory) is associated with subliminal activation of
      the motor system. This observation has led to the hypothesis that cortical
      activation during motor imagery may affect the acquisition of specific motor
      skills and help the recovery of motor function. In this paper, we describe a
      clinical protocol in which we use interactive tools to stimulate motor imagery in
      hemiplegic stroke patients, thereby helping them to recover lost motor function.
      The protocol consists of an inpatient and an outpatient phase, combining physical
      and mental practice. In the inpatient phase, patients are trained in a laboratory
      setting, using a custom-made interactive workbench (VR Mirror). After discharge,
      patients use a portable device to guide mental and physical practice in a home
      setting. The proposed strategy is based on the hypotheses that: (a) combined
      physical and mental practice can make a cost-effective contribution to the
      rehabilitation of stroke patients, (b) effective mental practice is not possible
      without some form of support, from a therapist (as in our inpatient phase) or
      from technology (as in the outpatient phase), (c) the inclusion of an outpatient
      phase will allow the patient to practice more often than would otherwise be
      possible, therefore increasing the speed and/or effectiveness of learning, and
      (d) the use of interactive technology will reduce the patient's need for skilled
      support, therefore improving the cost-effectiveness of training.

PMID- 15257834
TI  - Net-generation attributes and seductive properties of the internet as predictors
      of online activities and internet addiction.
AB  - Born between 1977 and 1997, Net-generation is the first generation to grow up
      surrounded by home computers, video games, and the Internet. As children of the
      Baby Boomers, the Internet is the medium of choice for the Net-geners. Based on
      the assumption that Net-generation has unique characteristics, this study
      examined (1) how Net-geners addicted to the Internet differ from the non-addicted
      and (2) how these attributes, together with the seductive properties of the
      Internet, are related to Internet addiction. Data were gathered from a
      probability sample of 699 Net-geners between the ages of 16 and 24. Results show
      that Net-geners addicted to the Internet tend to be young female students. Being
      emotionally open on the Net and a heavy user of ICQ were most influential in
      predicting Net-geners' problematic use of the Internet. Addicted Net-geners are
      also strongly linked to the pleasure of being able to control the simulated world
      in online games. The finding reinforces previous research that "dependents" of
      the Internet spend most of their time in the synchronous communication
      environment engaging in interactive online games, chat rooms, and ICQ for
      pleasure-seeking or escape, while "non-dependents" use information-gathering
      functions available on the Internet. Furthermore, Internet addicts tend to watch
      television significantly less, indicating a displacement effect on traditional
      media use for the Net-generation.

PMID- 15257835
TI  - Criticism or praise? The impact of verbal versus text-only computer feedback on
      social presence, intrinsic motivation, and recall.
AB  - The Computers Are Social Actors (CASA) paradigm asserts that human computer users
      interact socially with computers, and has provided extensive evidence that this
      is the case. In this experiment (n = 134), participants received either praise or
      criticism from a computer. Independent variables were the direction feedback
      (praise or criticism), and voice channel (verbal or text-only). Dependent
      variables measured via a computer-based questionnaire were recall, perceived
      ability, intrinsic motivation, and perceptions of the computer as a social
      entity. Results demonstrate that participants had similar reactions to computers
      as predicted by interpersonal communication research with participants who
      received text-only criticism reporting higher levels of intrinsic motivation,
      perceived ability, and recall. Additionally, the computer was seen as more
      intelligent. Implications for theory and application are discussed.

PMID- 15257836
TI  - Back from the beach but hanging on the telephone? English adolescents' attitudes
      and experiences of mobile phones and the internet.
AB  - Recently, a number of commentators have suggested that growth in use of the
      Internet may be slowing, and its impact may have been exaggerated. However, a
      disproportionate number of the nonusers tend to be those over the age of 50, and
      the young are most likely to go online eventually. Therefore, the most
      appropriate people to survey with regard to Internet use are adolescents and
      young adults who are likely to be the Internet users or nonusers of the future.
      This survey was conducted to find out more about the activities and opinions of
      secondary-school aged children who do, and do not, use the Internet. Mobile phone
      use was also examined in this survey as this has also shown a meteoric rise in
      adults and more particularly in young people. Generally, the survey revealed that
      children aged between 11 and 16 years old are quite comfortable with the
      Internet, use it a moderate amount and for a variety of purposes. However, boys
      were more likely to use the Internet than girls and sometimes for slightly
      different purposes. Reasons for not using the Internet generally revolved around
      a lack of access to equipment. Furthermore, a higher percentage of adolescents
      have mobile phones than adults and girls are more likely to own a mobile phone
      than boys. Mobile phones were also used for a variety of purposes, most notably
      making and receiving calls and text-messaging. The most common reasons for
      children not owning a mobile phone was because they had no need for one. Finally,
      a significant positive relationship between the use of emails and text messaging
      suggests that the mobile phone may supplement some of the previous functions of
      the Internet.

PMID- 15257839
TI  - The legacy of child maltreatment: long-term health consequences for women.
AB  - In 2001, over 903,000 children were victims of physical, sexual, or psychological
      maltreatment and neglect. Available retrospective and longitudinal data suggest
      that child maltreatment has a significant negative impact directly on women's
      physical and mental health in childhood, adolescence, and adulthood.
      Additionally, childhood maltreatment is a critical risk factor for physical and
      sexual victimization in adulthood, especially by an intimate partner. The harmful
      effects of victimization in adulthood among women are substantial, and the
      negative outcomes of adulthood victimization are especially pronounced when there
      is a history of childhood maltreatment. Therefore, in addition to the direct
      effects in childhood, child maltreatment appears to have an indirect effect on
      women's physical and mental health by increasing the risk for victimization
      which, in turn, has a direct negative impact on health. The results of existing
      empirical studies point to the importance of preventing child maltreatment and
      its short-term and long-term consequences. Intervening at an early stage may
      reduce a child's likelihood of developing long-term health problems, and also
      reduce the public health burden of child maltreatment by preventing future health
      problems and revictimization in adulthood with all its negative health
      consequences.

PMID- 15257840
TI  - Toward optimal health: the experts discuss therapeutic humor. Interview by Jodi
      R. Godfrey.

PMID- 15257842
TI  - Health promotion interventions for disadvantaged women: overview of the WISEWOMAN
      projects.
AB  - BACKGROUND: The Well-Integrated Screening and Evaluation for Women Across the
      Nation (WISEWOMAN) program aims to remove racial and ethnic disparities in health
      by addressing the screening and intervention needs of midlife uninsured women.
      This paper describes the WISEWOMAN program requirements, the design of the 12
      projects funded in 2002, the use of a standardized data reporting and analysis
      system, risk factors among participants, effective behavioral strategies, and
      plans for the future. METHODS: The WISEWOMAN demonstration projects are examining
      the feasibility and effectiveness of adding a cardiovascular disease (CVD)
      prevention component to the early detection of breast and cervical cancer. Women
      aged 40-64 are eligible if they are enrolled in the National Breast and Cervical
      Cancer Early Detection Program (NBCCEDP) in selected U. S. states and are
      financially disadvantaged and lack health insurance. The primary outcome measures
      are blood pressure, lipid levels, and tobacco use. Intermediate measures include
      self-reported diet and physical activity, measures of readiness for change, and
      barriers to behavior change. RESULTS: During 2002, the 10 projects that were
      fully operational screened 8164 financially disadvantaged women and developed
      culturally and regionally appropriate nutrition and physical activity
      interventions for a variety of racial and ethnic backgrounds. Twenty-three
      percent of the women screened had high total cholesterol, with 48% of these being
      newly diagnosed. Thirty-eight percent of the women had high blood pressure, with
      24% being newly diagnosed. Approximately, 75% of participants were either
      overweight or obese, and in some sites up to 42% were smokers. CONCLUSIONS: The
      WISEWOMAN demonstration projects have been successful at reaching financially
      disadvantaged and minority women who are at high risk for chronic diseases. These
      projects face challenges because they are generally implemented by safety net
      providers who have limited resources and staff to conduct research and
      evaluation. On the other hand, the findings from these projects will be
      especially informative in reducing health disparities because they are conducted
      in those settings where the most socially and medically vulnerable women receive
      care.

PMID- 15257843
TI  - Racial/ethnic disparities in coronary heart disease risk factors among WISEWOMAN
      enrollees.
AB  - BACKGROUND: We used the baseline data collected for the Well-integrated Screening
      and Evaluation for Women Across the Nation (WISEWOMAN) participants to provide a
      snapshot of cardiovascular disease (CVD) risk on enrollment and to address
      racial/ethnic disparities in the following CVD risk factors: body mass index
      (BMI), systolic and diastolic blood pressure, high-density lipoprotein (HDL) and
      total cholesterol, diabetes and smoking prevalence, 10-year coronary heart
      disease (CHD) risk, and treatment and awareness of high cholesterol,
      hypertension, and diabetes. METHODS: We used linear regression analysis to (1)
      assess the presence of racial/ethnic disparities and test whether existing
      disparities can be explained by (2) differences in individual characteristics or
      by (3) differences in individual and community characteristics. RESULTS: Our
      results reveal a high degree of CVD risk among the WISEWOMAN participants and
      statistically significant racial/ethnic disparities in risk factors. Black
      participants were at the greatest risk of CVD, and Hispanic and Alaska Native
      participants were healthier in terms of CVD risk than white participants. Some
      racial/ethnic disparities were explained by differences in individual and
      community characteristics, but other disparities persisted even after controlling
      for these factors. CONCLUSIONS: Because differences in community characteristics
      explain many of the racial/ethnic disparities in CVD risk factors, eliminating
      disparities may require community-wide interventions. Successful WISEWOMAN
      projects are likely to not only reduce CVD risk factors overall but also to
      lessen racial/ethnic disparities in these risk factors.

PMID- 15257844
TI  - The WISEWOMAN projects: lessons learned from three states.
AB  - BACKGROUND: The WISEWOMAN program provides chronic disease risk factor screening,
      lifestyle interventions, and referrals to financially disadvantaged women who
      participate in the National Breast and Cervical Cancer Early Detection Program
      (NBCCEDP). Three states (Arizona, Massachusetts, and North Carolina) participated
      in Phase One (1995-1998). METHODS: Using a case study approach, we reviewed
      documents and conducted telephone interviews to compare the three projects'
      design and execution. The interviews, carried out in mid-2002, involved a
      convenience sample of project coordinators, project directors, researchers, and
      one CDC project officer (n = 9). RESULTS: Many providers were overwhelmed by
      WISEWOMAN's research component and disliked its lack of flexibility. Researchers
      emphasized that high-quality evaluation requires resources and attention.
      Informants described the challenges of integrating WISEWOMAN with state BCCEDP
      programs that are in varying development stages and recommended changes in
      organizational culture and provider practices. Regarding implementation,
      informants emphasized the need for adequate and appropriate planning, buy-in,
      training, professional support, and outreach. Our sample also noted that
      WISEWOMAN projects tend to be labor intensive. CONCLUSIONS: WISEWOMAN projects
      face challenges of integrating clinical and lifestyle interventions, reaching
      beyond a focus on individuals, marshaling substantial resources, and introducing
      complex interventions into stretched healthcare environments. The three Phase One
      projects were deemed successful in reaching underserved women, developing a more
      comprehensive women's health model, strengthening linkages to primary healthcare,
      experimenting with innovative behavioral interventions, and tapping into women's
      roles as social support providers and family/community gatekeepers.

PMID- 15257845
TI  - Cardiovascular disease risk reduction: the Massachusetts WISEWOMAN project.
AB  - BACKGROUND: This report presents the effectiveness of the Massachusetts Well
      Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN)
      Project (MWWP) in reducing the cardiovascular disease (CVD) risk of uninsured and
      underinsured women aged > or =50. METHODS: Healthcare sites were randomly
      assigned to an enhanced intervention (EI) or minimum intervention (MI). Women
      enrolled at all sites received CVD risk factor screening, onsite counseling,
      education, referral, and follow-up as needed. Women enrolled at EI sites received
      additional services and specially designed interventions, including one-on-one
      nutritional and physical activity counseling and group activities, such as
      walking groups, nutrition classes, and cultural festivals. We report results for
      1443 women who attended the initial screening in 10 study sites. Blood pressure,
      total cholesterol, number of servings of fruits and vegetables, and level of
      moderate or vigorous physical activity were assessed at baseline and 12-month
      follow-up screenings. Baseline data were collected between March and June 1996;
      follow-up data were collected 12 months later. RESULTS: The comprehensive
      screenings significantly lowered the overall prevalence of hypertension,
      resulting in a 7% reduction in high blood pressure among women at the EI sites (p
      = 0.02) and a 9% reduction at MI sites (p = 0.009). A significantly greater
      percentage of women became physically active at the EI sites (18%) than at the MI
      sites (6%) (p = 0.04). CONCLUSIONS: MWWP is a promising model for providing
      comprehensive preventive healthcare to uninsured and underinsured women.

PMID- 15257847
TI  - Effects of a tailored follow-up intervention on health behaviors, beliefs, and
      attitudes.
AB  - BACKGROUND: The high rates of relapse that tend to occur after short-term
      behavioral interventions indicate the need for maintenance programs that promote
      long-term adherence to new behavior patterns. Computer-tailored health messages
      that are mailed to participants or given in brief telephone calls offer an
      innovative and time-efficient alternative to ongoing face-to-face contact with
      healthcare providers. METHODS: Following a 1-year behavior change program, 22
      North Carolina health departments were randomly assigned to a follow-up
      intervention or control condition. Data were collected from 1999 to 2001 by
      telephone-administered surveys at preintervention and postintervention for 511
      low-income, midlife adult women enrolled in the Well-Integrated Screening and
      Evaluation for Women Across the Nation (WISEWOMAN) program at local North
      Carolina health departments. During the year after the behavior change program,
      intervention participants were mailed six sets of computer-tailored health
      messages and received two computer-tailored telephone counseling sessions. Main
      outcomes of dietary and physical activity behaviors, beliefs, and attitudes were
      measured. RESULTS: Intervention participants were more likely to move forward
      into more advanced stages of physical activity change (p = 0.02); control
      participants were more likely to increase their level of dietary social support
      at follow-up (p = 0.05). Both groups maintained low levels of reported saturated
      fat and cholesterol intake at follow-up. No changes were seen in physical
      activity in either group. CONCLUSIONS: Mailed computer-tailored health messages
      and telephone counseling calls favorably modified forward physical activity stage
      movement but did not appreciably affect any other psychosocial or behavioral
      outcomes.

PMID- 15257846
TI  - Provider counseling, health education, and community health workers: the Arizona
      WISEWOMAN project.
AB  - BACKGROUND: The Arizona Well-Integrated Screening and Evaluation for Women Across
      the Nation (WISEWOMAN) project used provider counseling, health education, and
      community health workers (CHWs) to target chronic disease risk factors in
      uninsured, primarily Hispanic women over age 50. METHODS: Participants were
      recruited from two Tucson clinics participating in the National Breast and
      Cervical Cancer Early Detection Program (NBCCEDP). Women were randomly assigned
      into one of three intervention groups: (1) provider counseling, (2) provider
      counseling and health education, or (3) provider counseling, health education,
      and CHW support. At baseline and 12 months (1998-2000), participants were
      measured for height, weight, waist and hip circumference, and blood pressure.
      Blood tests were conducted to check blood glucose, cholesterol, and triglyceride
      levels. At each time point, participants also completed 24-hour dietary recalls
      and questionnaires focusing on their physical activity levels. RESULTS: A total
      of 217 women participated in baseline and 12-month follow-up. Three fourths were
      Hispanic. All three intervention groups showed an increase in self-reported
      weekly minutes of moderate-to-vigorous physical activity, with no significant
      differences between the groups. Significantly more women who received the
      comprehensive intervention of provider counseling, health education, and CHW
      support progressed to eating five fruits and vegetables per day, compared with
      participants who received only provider counseling or provider counseling plus
      health education. CONCLUSIONS: All three interventions increased moderate-to
      vigorous physical activity but not fruit and vegetable consumption. The
      intervention group with provider counseling, health education, and CHW support
      significantly increased the number of women meeting national recommendations for
      fruit and vegetable consumption.

PMID- 15257848
TI  - Heart disease prevention for Alaska Native women: a review of pilot study
      findings.
AB  - BACKGROUND: Although historically Alaska Native women have had a relatively low
      incidence of cardiovascular disease (CVD), this pattern has changed dramatically
      in recent years. Alaska Native leaders have identified decreasing cardiovascular
      risk as an intervention priority. METHODS: From October 2000 to April 2001,
      Southcentral Foundation, an Alaska Native-owned and managed health corporation in
      Anchorage, conducted a pilot randomized controlled trial of a heart disease
      prevention program tailored for Alaska Native women. The aim was to assess
      feasibility and cultural acceptability and to develop enrollment procedures. Of
      76 women who enrolled, 44 were randomized to the intervention group. Thirty-seven
      of 44 attended at least two intervention sessions, 23 completed prequestionnaires
      and postquestionnaires, and 27 returned for 12-month follow-up screening. Thirty
      of 32 control group participants returned for 12-month follow-up screening. The
      intervention included 12 weekly sessions on lifestyle change and goal setting. At
      baseline and 12 months, participants' height, weight, resting blood pressure,
      fasting lipid levels, and blood glucose were measured. At sessions 1 and 12,
      participants completed assessments regarding diet, physical activity, tobacco
      use, and psychosocial status. RESULTS: At 12 weeks, significant improvements were
      noted in moderate walking and physical activity self-efficacy. Also observed was
      substantial movement from the contemplation and preparation stages to the action
      stage regarding physical activity and heart-healthy eating. CONCLUSIONS: Although
      the small sample size precludes drawing conclusions about the intervention's
      effect, participants reported lifestyle and psychosocial changes. The pilot study
      resulted in protocol changes that improved the design and implementation of a
      subsequent large-scale study.

PMID- 15257849
TI  - A replicable process for redesigning ethnically relevant educational materials.
AB  - BACKGROUND: To serve the populations targeted by Well-Integrated Screening and
      Evaluation for Women Across the Nation (WISEWOMAN) effectively, healthcare
      providers need educational materials that are evidence based and ethnically
      relevant and can be easily incorporated into busy clinic settings. We describe a
      replicable process used to redesign and tailor physical activity and diet
      education materials for African American women in the southeastern United States.
      METHODS: The process consists of seven phases. Quantitative and qualitative
      analyses were used on data gathered in 2000 from two expert panels and eight
      focus groups. RESULTS: Expert panelists preferred materials perceived to be high
      quality, easy to understand, organized to facilitate use by healthcare providers,
      and with content relevant to African American women. Focus group participants
      were mostly concerned with the visual appeal and content of educational
      materials. They liked high-quality materials that are brief; avoid jargon and use
      simple language, bright colors, and photographs; and provide useful information
      that acknowledges the context of their lives, including their family roles.
      CONCLUSIONS: The redesign process can produce ethnically and culturally
      appropriate educational materials for use by WISEWOMAN providers and other
      healthcare providers in conjunction with cardiovascular (CVD) risk reduction and
      behavioral counseling. To be effective, materials must address the needs and
      concerns of both providers and patients.

PMID- 15257850
TI  - Extending the reach of public health nutrition: training community practitioners
      in multilevel approaches.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a major public health concern in the
      United States. We developed an annual training course, Nutrition and Public
      Health, A Course for Community Practitioners (NPH), to address the identified
      training needs of state staff responsible for designing and implementing the Well
      Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN)
      program and to support other health professionals working in programs that
      address chronic disease prevention and management. METHODS: After conducting a
      needs assessment with state-level WISEWOMAN staff in 2001 to identify topics of
      interest, we formed an advisory committee to provide guidance on topics,
      theoretical frameworks, training concerns, and multilevel intervention
      approaches. The first week-long training course, which included an intensive
      field practicum, was implemented in the fall of 2002. RESULTS: Participants rated
      three fourths of the elements listed in a posttraining evaluation as a course
      strength, giving particularly high ratings to various indicators of course
      quality (100%) and networking opportunities (95%). Just over half (55%) rated the
      field practicum as a course strength. Four fifths (83%) of participants responded
      to a 6-month follow-up evaluation, and most indicated that the course had
      increased their knowledge and skills and increased their confidence in planning
      programs. CONCLUSIONS: Unique features of the course include its suitability for
      public health practitioners not previously trained in nutrition, its promotion of
      multilevel interventions, and its focus on CVD risk reduction and nutrition
      interventions for underinsured and uninsured populations.

PMID- 15257851
TI  - Implementing the WISEWOMAN program in local health departments: staff attitudes,
      beliefs, and perceived barriers.
AB  - BACKGROUND: Although most health departments recognize the need for programs to
      reduce the risk of cardiovascular disease (CVD) among older, low-income women,
      they face numerous barriers to successfully implementing such programs. This
      paper explores counselors' attitudes and beliefs about patients and perceived
      barriers to implementing the North Carolina Well-Integrated Screening and
      Evaluation for Women Across the Nation (WISEWOMAN) program. METHODS: Health
      departments were assigned to provide patients with either an enhanced
      intervention (EI) or a minimum intervention (MI). Cross-sectional baseline and 12
      month follow-up surveys were completed by health department counselors designated
      to deliver the MI or EI. Both surveys addressed counselors' beliefs about
      patients' motivation and attitudes, their counseling practices, and their
      personal diet and physical activity behaviors and attitudes. The follow-up survey
      also addressed opinions about the feasibility of long-term WISEWOMAN
      implementation. RESULTS: Counselors were skeptical about patients' motivation to
      improve their lifestyle, citing high perceived cost and burden. At follow-up, EI
      counselors reported having higher self-efficacy for counseling, incorporating
      more behavioral change strategies, and spending more time counseling than did
      counselors at MI sites. They were also more likely to report making healthful
      personal lifestyle choices. All counselors identified lack of time as a major
      barrier to counseling, and most cited obtaining low-cost medications for
      patients, ensuring that patients made follow-up visits, and implementing the
      program with existing staff as key challenges to the long-term sustainability of
      WISEWOMAN. CONCLUSIONS: Our findings provide insight into the organizational
      challenges of implementing a CVD risk-reduction program for low-income women. We
      discuss ways in which intervention and training programs can be improved.

PMID- 15257853
TI  - Using success stories to share knowledge and lessons learned in health promotion.
AB  - BACKGROUND: Compelling success stories, rich with details about real-life events
      and people, are a tool that health agencies can use to convey how their health
      promotion programs work, why they are successful, what lessons they have learned,
      and how others can launch similar programs. Success stories describe project
      accomplishments that are not easily captured by quantitative evaluation methods,
      such as surveys. METHODS: Although success stories have not been widely used in
      public health, the North Carolina Department of Health and Human Services
      developed a series of stories, the Community Change Chronicles, to highlight
      environmental and policy changes that promote cardiovascular health. In 2003, the
      Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN)
      program used the Community Change Chronicles as a model to develop success
      stories about WISEWOMAN projects. RESULTS: WISEWOMAN Works: A Collection of
      Success Stories from Program Inception Through 2002 includes 12 stories and
      offers advice on how to create and use success stories in public health. This
      paper reviews the rationale for developing the stories, presents one success
      story as an example, and describes the process used to gather information, write
      the stories, and produce a resource for others interested in developing success
      stories. We also discuss how the WISEWOMAN success stories are being used to
      promote women's health and cardiovascular health. CONCLUSIONS: As the WISEWOMAN
      experience suggests, healthcare providers and organizations can use success
      stories to gain support for successful activities, inform the public about
      program benefits, complement other quantitative and qualitative evaluation
      methods, and publicly acknowledge the contributions of staff and organizational
      partners.

PMID- 15257852
TI  - Integrating preventive health services within community health centers: lessons
      from WISEWOMAN.
AB  - BACKGROUND: Well-Integrated Screening and Evaluation for Women Across the Nation
      (WISEWOMAN) provides low-income, underserved women ages 40-64 with risk factor
      screening and lifestyle intervention and referral services to prevent
      cardiovascular disease (CVD). Integrating WISEWOMAN's services with the
      culturally appropriate medical care and support services offered by community
      health centers may improve the program's ability to reduce CVD burden among
      underserved women. METHODS: We conducted a formative assessment of the perceived
      opportunities, challenges, and strategies associated with integrating WISEWOMAN
      into community health center settings. A panel of stakeholders that included
      health center and WISEWOMAN representatives was convened in 2002, and a
      semistructured discussion guide was used to elicit perspectives about
      integration. We also conducted an in-depth review of WISEWOMAN's history of
      collaboration with health centers in North Carolina. RESULTS: Stakeholders
      perceived a clear need for integrating WISEWOMAN within health center settings,
      indicating that centers have few other resources to expand preventive services
      delivery and offer effective lifestyle interventions for underserved populations.
      Perceived barriers to integration included competing demands on health center
      resources, difficulties hiring staff for new programs, and administrative burdens
      associated with data collection and reporting. Experiences within North
      Carolina's WISEWOMAN project demonstrate, however, that lifestyle interventions
      can be designed in ways that facilitate integration by health centers.
      CONCLUSIONS: Integration strategies need to be tailored to the resources, skills,
      and capacities available within health centers. As health centers and WISEWOMAN
      projects gain more experience in collaborating, additional research should be
      conducted to identify how best to achieve integration within specific
      institutional and community contexts.

PMID- 15257854
TI  - Evaluation of public health demonstration programs: the effectiveness and cost
      effectiveness of WISEWOMAN.
AB  - BACKGROUND: In today's healthcare environment, public health resources are
      scarce. Thus, interventions to improve the public's health must be rigorously
      evaluated to ensure that they make the best use of available resources. METHODS:
      The Centers for Disease Control and Prevention (CDC) provides a general framework
      for program evaluation. This paper presents additional details on several key
      evaluation areas within CDC's framework. RESULTS: Successful evaluations will be
      built into the program design; will be multifaceted, incorporating both
      quantitative and qualitative methods; will assess both process and outcome
      measures; and will engage stakeholders to ensure utility of results. CONCLUSIONS:
      Well-planned evaluations can lead to less burdensome yet more effective
      assessment and better program performance and can increase the knowledge base for
      health promotion practice.

PMID- 15257855
TI  - Expanding the evidence for health promotion: developing best practices for
      WISEWOMAN.
AB  - Implementing effective programs to prevent chronic disease holds the promise of
      reducing morbidity and mortality, reducing health disparities, and promoting
      health. Yet many programs have demonstrated success only in highly controlled
      research settings and few address the needs of low-income, uninsured, minority
      women. Well-Integrated Screening and Evaluation for Women Across the Nation
      (WISEWOMAN), a demonstration program funded by the Centers for Disease Control
      and Prevention (CDC), that provides chronic disease risk factor screening and
      lifestyle interventions for low-income, 40-64-year-old women is learning from our
      own successful programs but is also charting new territory. As the CDC, state
      health departments, tribal organizations, and other WISEWOMAN partners approach
      the end of the first decade of WISEWOMAN demonstration projects, we are seeking
      to understand what has worked and what has not. This paper describes the
      rationale and proposed methodology for assessing best practices in the WISEWOMAN
      program through a participatory process that will examine scientific evidence and
      quantitative and qualitative program data. By emphasizing practicality in
      addition to scientific rigor, we are expanding the base of evidence considered to
      identify effective approaches for reducing cardiovascular disease (CVD) risk in
      financially disadvantaged, ethnically diverse women. Results of the 3-year
      project will be disseminated in a format intended to encourage programs to select
      and adapt those strategies best suited to their particular contexts.

PMID- 15257856
TI  - Building capacity to prevent and control chronic disease in underserved
      communities: expanding the wisdom of WISEWOMAN in intervening at the
      environmental level.

PMID- 15257857
TI  - Angiotensin II: an amplifier of cardiovascular risk.

PMID- 15257858
TI  - Clinical trials report. VALIANT: another milestone for angiotensin receptor
      blockers.

PMID- 15257859
TI  - Are angiotensin receptor blockers neuroprotective?
AB  - Stroke is one of the leading causes of invalidism and death in the industrialized
      world. Among others, the renin- angiotensin system (RAS) has been implicated in
      the pathogenesis and outcome of ischemic events, including stroke. Angiotensin II
      (Ang II), the major effector peptide of the RAS, exerts most of its well-defined
      physiologic and pathophysiologic actions, including those on the central and
      peripheral nervous system, through its Ang II type 1 (AT1) receptor subtype. This
      receptor not only contributes to stroke-related pathologic mechanisms (eg,
      hypertension, atherothrombosis, and cardiac hypertrophy) but also may be involved
      in postischemic damage to the brain. However, it has also been demonstrated that
      Ang II, via its AT2 receptor subtype, accelerates neuronal tissue regeneration
      after injury. In this article, we review the experimental evidence supporting the
      notion that blockade of brain AT1 receptors can be beneficial with respect to
      stroke incidence and outcome. We further delineate how AT2 receptors could be
      involved in neuronal regeneration following brain injury, such as stroke. In
      doing so, we also attempt to shed some light on the mechanisms by which AT1
      receptor blockers, which leave the AT2 receptor unopposed, might exert protective
      actions in brain ischemia.

PMID- 15257860
TI  - Combination therapy as first-line treatment for hypertension.
AB  - With the cut-off point between "normal" and "high" blood pressure (BP) being
      pushed increasingly downward, especially for patients with multiple
      cardiovascular risk factors, most hypertensives need more than one
      antihypertensive agent to reach their target BP. In this article, we examine the
      rationale for combining drugs from different classes that have synergistic or
      additive effects and properties that might offset one another's adverse
      hemodynamic and/or metabolic reactions. We suggest circumstances in which the
      initiation of therapy with a fixed two-drug combination might be preferable to
      the usual practice of starting with monotherapy followed by upward titration and
      addition of other agents, and we briefly review the existing fixed drug
      combinations. We end with the intriguing and provocative notion of the future
      "polypill," a fixed combination of agents addressing various components of the
      metabolic syndrome as well as other coexisting common risk factors in both high
      risk patients with conditions requiring polypharmacy and in healthy, asymptomatic
      individuals.

PMID- 15257861
TI  - Hypertension management in patients with diabetic nephropathy.
AB  - Treatment of hypertension, to reverse and delay proteinuria progression and
      kidney failure, is the primary focus of medical management in patients with
      diabetic nephropathy. The initial choice for hypertension treatment in those with
      early nephropathy involves agents that block the renin-angiotensin system.
      However, it is not clear what the best choices for further drug therapy
      management are, because there are few data concerning the impact that
      antihypertensive drug combinations have on hard clinical outcomes, such as
      preventing the need for dialysis, and death. Patients usually require several
      drugs for controlling hypertension, which becomes harder to control as
      nephropathy progresses. In this review, it is suggested that quantitatively
      tracking proteinuria to guide therapy and a broad focus on the cardiovascular and
      renal end points are important for best outcomes in patients. Strategies may vary
      based on stage of disease, comorbidities, and age. Therapies not directed
      specifically at hypertension may also significantly aid hypertension management
      in prevention of progressive nephropathy, comorbidities, and mortality.

PMID- 15257863
TI  - Clinical trials report. Consequences of new-onset diabetes during the treatment
      of hypertension.

PMID- 15257862
TI  - Mineralocorticoid receptor antagonists and hypertension: is there a rationale?
AB  - Accumulating evidence indicates that aldosterone is involved in cardiovascular
      disease by inducing inflammation in the presence of moderate amounts of salt in
      the diet. Spironolactone and eplerenone are the mineralocorticoid receptor (MR)
      antagonists currently available for the treatment of hypertension. They have
      similar safety and antihypertensive efficacy. The advantage of eplerenone is the
      lower incidence of anti-androgenic and progestational side effects. The rationale
      for using MR blockade in the treatment of hypertension is threefold: the evidence
      of antihypertensive efficacy, the phenomenon of "aldosterone escape" occurring
      with angiotensin-converting enzyme inhibitor and angiotensin-receptor blockade
      therapy, and the compelling evidence that MR antagonism reduces target-organ
      damage in hypertensive patients and improves survival in patients with
      cardiovascular disease. Thus, blockade of the MR may be very useful in many
      patients with hypertension, particularly those at risk for or having evidence of
      target-organ damage.

PMID- 15257864
TI  - Compelling drug indications in diabetic and nondiabetic nephropathy.
AB  - To halt progression of renal disease, the combination of several interventional
      strategies is recommended. The most important components comprise lowering of
      systolic blood pressure to approximately 120 mm Hg; providing pharmacologic
      blockade of the renin-angiotensin system by angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers; and reducing proteinuria to rates of
      less than 1 g/d.

PMID- 15257865
TI  - Combined antihypertensive and lipid-lowering treatment.
AB  - Hypertension and hypercholesterolemia are frequently associated, and their
      treatment is proven to reduce cardiovascular risk. Current guidelines on
      cardiovascular prevention strongly recommend treating both disorders.
      Unfortunately, the low treatment and control rates, combined with the high
      prevalence of both conditions, still contribute to the high burden of
      cardiovascular disease in Western countries. In the past 5 years, many studies
      evaluating the benefit of combined antihypertensive and lipid-lowering treatment
      on endothelial dysfunction, coronary atherosclerosis, hypertension control, and
      on primary and secondary prevention of cardiovascular events have been published.
      In this article, we discuss and critically evaluate the available evidence on the
      potential benefits of combined antihypertensive and lipid-lowering treatment.

PMID- 15257866
TI  - Protection against stroke and dementia: an update on the latest clinical trial
      evidence.
AB  - Recent meta-analyses have examined the relationship between lowering blood
      pressure (BP) and reducing the risk for stroke and dementia. Studies have shown
      that drug therapy that successfully reduces systolic BP by only 10 mm Hg results
      in significant protection against stroke. Controversy exists regarding the most
      effective regimen, with supporters for the standards of diuretics and beta
      blockers, or angiotensin-converting enzyme inhibitors and calcium-channel
      blockers, pitted against the increasing evidence of the effectiveness of
      angiotensin-receptor blockers or statins. Additionally, the most effective
      strategy for delivery of BP-reducing therapy is being examined, with some studies
      supporting use of standards for primary prevention of stroke and reserving the
      newer drugs for secondary prevention. Ultimately, however, all agree that for
      patients with the highest risk for cardiovascular and cerebrovascular
      complications, the strategy of intervention is immaterial, and drug therapy,
      including low-dose aspirin, is vital.

PMID- 15257867
TI  - Lead-induced hypertension: role of oxidative stress.
AB  - Chronic, low-level lead exposure causes hypertension in both animals and humans.
      The pathogenesis of lead-induced hypertension is multifactorial, including such
      diverse mechanisms as: inactivation of endogenous nitric oxide and downregulation
      of soluble guanylate cyclase by reactive oxygen species (ROS), leading to a
      functional deficiency in nitric oxide; heightened sympathetic activity and plasma
      norepinephrine together with depressed vascular and elevated renal beta
      adrenergic receptor density; elevated plasma angiotensin-converting enzyme (ACE)
      activity, plasma renin activity (PRA), angiotensin II (Ang-II), and aldosterone
      levels; increased kininase I and kininase II activities; lead-induced inhibition
      of vascular smooth muscle Na(+)-K+ ATPase, leading to a rise in cellular Na+ and,
      hence, Ca2+; and a possible rise in endothelin and thromboxane generation. In
      this article, we present an overview of the epidemiology and proposed underlying
      mechanisms of lead-induced hypertension.

PMID- 15257868
TI  - The relationship between exposure to violence and blood pressure mechanisms.
AB  - Although previous research has indicated a link between environmental stress and
      essential hypertension, little is known about the role of violence exposure on
      risk for developing essential hypertension. Violence exposure, defined as
      experiencing, witnessing, or hearing about violence in the home, school, or
      neighborhood, is a serious societal problem. Approximately 70% of inner-city
      youth have been victims of violent acts, and approximately 85% of these youths
      report having witnessed violent acts. In this review, several possible paths are
      proposed to explain the link between exposure to violence and cardiovascular
      health outcomes (eg, physiologic and psychosocial). Several contextual models are
      outlined, and a review of the empirical evidence suggests that chronic
      environmental stress (eg, violence exposure) might play a role in the development
      of essential hypertension. The mechanisms underlying the effects of violence
      exposure on blood pressure are unknown, although preliminary evidence suggests
      that elevated sympathetic nervous system activity may be involved. Several
      possible psychosocial mechanisms are outlined that might also link violence
      exposure to physiologic blood pressure-related mechanisms. Prevention and
      intervention efforts to reduce community violence are reviewed, and a call is
      made for encouraging further research on this critical topic.

PMID- 15257869
TI  - Aldosterone-receptor antagonism and end-stage renal disease.
AB  - Blockade of aldosterone effect with either spironolactone or eplerenone is an
      approach that is being used more frequently in the treatment of hypertension and
      congestive heart failure; however, sparse information exists pertaining to
      efficacy or side-effects of this line of treatment for patients with chronic
      kidney disease and/or end-stage renal disease (ESRD). Hyperkalemia is, by far,
      the most worrisome complication of therapy with either of these compounds and,
      not surprisingly, hinders their use in moderate-to-advanced renal failure.
      However, patients with anuric ESRD should theoretically not be at risk for
      hyperkalemia. To this end, pilot safety studies with aldosterone-receptor
      antagonists in ESRD patients have begun. These studies imply that spironolactone
      can be safely used in carefully selected and closely monitored patients.
      Eplerenone has not been studied in ESRD in a therapeutic or safety capacity.
      Additional studies are needed with these compounds in the ESRD population before
      their use can be considered safe.

PMID- 15257870
TI  - German-Austrian recommendations for HIV-therapy in pregnancy: update May 2003.
AB  - In Germany during the past years about 200-250 HIV infected pregnant women
      delivered a baby per year, a number that is currently increasing. To determine
      the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is
      recommended in Germany and Austria as part of prenatal care. In those cases,
      where HIV infection was known during pregnancy, since 1995 the rate of vertical
      transmission of HIV was reduced to 1-2%. - This low transmission rate has been
      achieved by the combination of anti-retroviral treatment of pregnant women,
      elective caesarean section before onset of labor, anti-retroviral post exposition
      prophylaxis in the newborn and refraining from breast-feeding by the HIV infected
      mother. To keep pace with new results in research, approval of new anti
      retroviral drugs and changes in the general treatment recommendations for HIV
      infected adults, in 1998 and 2001 an interdisciplinary consensus meeting was
      held. Gynaecologists, infectious disease specialists, pediatricians,
      pharmacologists, virologists and members of the German AIDS Hilfe (NGO) were
      participating in this conference to update the prevention strategies. A third
      update became necessary in 2003. The updating process was started in January 2003
      and was terminated in July 2003. The guidelines provide new recommendations on
      the indication and the starting point for HIV-therapy in pregnancies without
      complications, drugs and drug combinations to be used preferably in these
      pregnancies and updated information on adverse effects of anti-retroviral drugs.
      Also the procedures for different scenarios and risk constellations in pregnancy
      have been specified again. - With these current guidelines in Germany and Austria
      the low rate of vertical HIV-transmission should be further maintained or even
      further lowered.

PMID- 15257871
TI  - Therapy of hepatitis C in HIV-coinfection.
AB  - One third of all European and American HIV-patients are coinfected with hepatitis
      C. HIV accelerates hepatitis C virus liver disease especially when HIV-associated
      immune deficiency progresses. Indeed, liver cirrhosis rate is five times higher
      in HIV/HCV-coinfected patients than in HCV-monoinfected patients. With the
      introduction of pegylated interferon and ribavirin combination therapy sustained
      virological response rates of up to 40 % could be obtained in HIV/HCV-coinfected
      individuals. Moreover, cohort analyses could demonstrate that with the use of
      highly active antiretroviral therapy (HAART) an improved course of hepatitis C
      and a reduction in liver disease-associated mortality can be achieved. Under
      consideration of the increased rate of hepatotoxicity due to the presently
      available antiretroviral treatment regimens in HIV/HCV coinfected patients,
      however, the development of treatment strategies and guidelines for management of
      hepatitis coinfection in HIV remains of great clinical significance.

PMID- 15257872
TI  - Whole-body imaging with PET/MRI.
AB  - Whole-body positron emission tomography (PET) scanning with the radiolabeled
      glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ( superset 18 F-FDG)
      can identify areas of cancerous involvement and distinguish malignant from benign
      lesions and therefore, plays an important role in the diagnosis and management of
      patients with cancer. PET facilitates the evaluation of metabolic and molecular
      characteristics of a wide variety of cancers, but it is limited in its ability to
      visualize anatomical structures. Whole-body magnetic resonance imaging (MRI) is a
      promising diagnostic modality for the diagnosis and management of patients with
      cancer, because of its high anatomical resolution. Whole-body PET and whole-body
      MRI allow to evaluate both the primary tumor and for the presence of metastasis
      at the same time. The combination of these two excellent diagnostic imaging
      modalities into a single scanner offers several advantages in comparison to PET
      and MRI alone. A hybrid PET/MRI facilitates the accurate registration of
      metabolic and molecular aspects of the diseases with exact correlation to
      anatomical findings, improving the diagnostic value in identifying and
      characterizing of malignancies and tumor staging. Thus, hybrid PET/MRI could be a
      very important diagnostic imaging modality in oncological applications in the
      decades to come, and possibly for use in cancer screening and cardiac imaging.

PMID- 15257873
TI  - Proliferation of cultured human gingival fibroblasts caused by isradipine, a
      dihydropyridine-derivative calcium antagonist.
AB  - As it was reported earlier that isradipine, a Ca superset 2+ antagonist of
      dihydropyridine derivative class, caused regression of nifedipine-induced
      hyperplasia of human gingiva, experiments were performed to examine whether or
      not isradipine would solely inhibit the proliferation of cultured gingival
      fibroblasts. Normal human gingival fibroblast Gin-1 cells were used to test the
      impact of this medication. Fibroblast proliferation in the presence of isradipine
      (10 microM) was examined by using the reagent water-soluble tetrazolium-1 (WST
      1). The level of basic fibroblast growth factor (bFGF) in the cell-free
      supernatant of each well was determined by using an enzyme-linked immunosorvent
      assay (ELISA) kit. The production of type I collagen was assayed by ELISA.
      Isradipine significantly enhanced the cell proliferation from the second day of
      the culture period. Also, isradipine raised the level of bFGF in the culture
      medium. The same concentration, also significantly enhanced the production of
      type I collagen. In conclusion, we were able to prove that isradipine causes the
      proliferation of cultured gingival fibroblasts as well as other dihydropyridine
      derivative Ca superset 2+ antagonists do. In order to prevent the gingival
      overgrowth, it is advisable to be very careful in the use of isradipine as a
      therapy for hypertension and other indications.

PMID- 15257874
TI  - Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in
      tumor patients before and during therapy with an aqueous mistletoe extract.
AB  - Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and
      these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a
      new chitin-binding mistletoe lectin (cbML) has been isolated and structurally
      characterized in these extracts. Aim of the present study was, therefore, to
      evaluate whether this cbML also affects immunocompetent cells and can for
      instance activate B-cells to produce anti-cbML-specific antibodies. Sera from
      patients with different tumors who were treated with the mistletoe extract
      ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and
      after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3,
      and cbML, isolated from a single mistletoe plant collected from an apple tree
      (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies
      already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the
      18 anti-cbML negative patients before therapy 54% developed these antibodies
      during therapy, and there was a significant increase in anti-cbML antibody
      titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the
      25 patients being negative before therapy. These data indicate that cbML can
      induce immunological responses in patients treated with mistletoe extracts,
      although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies
      can be observed in a low incidence also in individuals, not having yet received
      mistletoe therapy.

PMID- 15257875
TI  - First results of Lichtenstein hernia repair with Ultrapro-mesh as cost saving
      procedure--quality control combined with a modified quality of life questionnaire
      (SF-36) in a series of ambulatory operated patients.
AB  - There are about 200,000 hernia repairs per year in Germany and about 770,000 in
      the U.S. In the United States most hernia repairs (80-90%) are performed as day
      surgery procedure; 90% of operations are open herniorrhaphies with mesh. Quality
      control includes the registration of complications, recurrence, and quality of
      life. In a prospective study 50 consecutive patients with inguinal hernia
      eligible for open mesh repair (modified Lichtenstein hernia repair), mostly Nyhus
      III and IV classification, were operated using light-weight Ultrapro-mesh
      (monocryl-prolene-composite, Ethicon Products), and interviewed 10 days after the
      operation according to a modified SF-36 questionnaire. Patients were examined
      three months later. There were 29 direct hernias, 21 combined (direct and
      indirect) hernias, 8 indirect hernias; 8 patients had hernias on both sides. 8
      patients (16%) presented with recurrent hernias, mostly suture or laparoscopic
      repairs before. There were no intra-operative complications. 2 patients suffered
      from a moderate haematoma, which did not necessitate a surgical repair, after
      accidental intake of aspirin preoperatively in one case and after preoperative
      low-molecular-weight heparin prophylaxis. There were no other complications. All
      50 patients (100%) had returned the questionnaire. 38 patients (78%) reported no
      or mild pain; only one patient (2%) suffered from severe pain, none had very
      severe pain. 32 patients (64%) applied no pain medication or only for 48 hours;
      only one patient (2%) used pain medication for more than 14 days. 34 patients
      (68%) admitted that their health status improved after the operation; 11 patients
      (22%) with good or very good health status indicated no change in health. Follow
      up examination of the patients three months after the operation did not detect
      any recurrence. 49 patients (98%) were free of pain or restriction; one patient
      (2%) continued to have chronic pain which developed after two laparoscopic
      herniotomies performed at a different clinic before. There was no sign of mesh
      related complication. The Ultrapro-mesh has been well accepted by the patients.
      In conclusion, open mesh repair according to Lichtenstein is safely done in
      specialised ambulatory day surgery clinics. Most patients benefit from this form
      of treatment according to a quality of life audit. The new light-weight mesh
      Ultrapro contributes to the improvement of hernia repair. There is evidence that
      ambulatory open mesh repair should be the method of choice for primary inguinal
      hernia. If in Germany an equal proportion of hernia repair as in the United
      States would be done as ambulatory procedure (80-90%), there would be an annual
      cost saving of several hundred million Euro.

PMID- 15257876
TI  - Ultrasound in emergency patients: better detection of free intraabdominal fluids
      by the use of tissue harmonic imaging.
AB  - BACKGROUND: Ultrasound examination is one of the main investigative procedures in
      emergency patients who are hospitalized due to abdominal pain. Detectable free
      fluid collections are important hints to the definite, sometimes life-threatening
      diagnosis, but their detection in cases of only small amounts is difficult to
      perform by conventional sonography. PATIENTS AND METHODS: We report about 25
      cases of patients who suffered from acute abdominal pain and who were presented
      as emergency patients to our department of ultrasound. First, the examination was
      performed by conventional sonography (3.4 MHz). Only with the additional tissue
      harmonic imaging (THI, 2.3 MHz, pulse inversion) thin borders of free fluids
      around the liver or other abdominal organs (gallbladder, spleen, pancreas, bowel)
      could be detected leading to other important diagnostic or therapeutic steps. In
      this way, the diagnosis of pancreatitis, cholezystitis, peritonitis, peritoneal
      carcinosis, ascites (liver cirrhosis, serositis, postoperative status after
      laparotomy), bleeding or paralytic ileus could be elucidated. CONCLUSION: THI
      sonography improves the detection of small amounts of free abdominal fluid
      collections. Therefore, this technique is helpful in the diagnostic procedure of
      emergency patients.

PMID- 15257877
TI  - PET/CT: fundamental principles.
AB  - Positron emission tomography (PET) facilitates the evaluation of metabolic and
      molecular characteristics of a wide variety of cancers, but is limited in its
      ability to visualize anatomical structures. Computed tomography (CT) facilitates
      the evaluation of anatomical structures of cancers, but can not visualize their
      metabolic and molecular aspects. Therefore, the combination of PET and CT
      provides the ability to accurately register metabolic and molecular aspects of
      disease with anatomical findings, adding further information to the diagnosis and
      staging of tumors. The recent generation of high performance PET/CT scanners
      combines a state of the art full-ring 3D PET scanner and a high-end 16-slice CT
      scanner. In PET/CT scanners, a CT examination is used for attenuation correction
      of PET images rather than standard transmission scanning using superset 68 Ge
      sources. This reduces the examination time, but metallic objects and contrast
      agents that alter the CT image quality and quantitative measurements of
      standardized uptake values (SUV) may lead to artifacts in the PET images. Hybrid
      PET/CT imaging will be very important in oncological applications in the decades
      to come, and possibly for use in cancer screening and cardiac imaging.

PMID- 15257878
TI  - Serial magnet resonance angiography in patients with vasculitis and vasculitis
      like angiopathy of the central nervous system.
AB  - The purpose of the study was to examine the value of the non-invasive magnet
      resonance angiography (MRA) in the follow-up of cerebral vasculitis (CV) and
      vasculitis-like angiopathy. We performed follow-up MRA (TOF 3D), MRI and
      transcranial doppler ultrasound (TCD) in the patients with isolated angiitis of
      the CNS (2/6), Crohn-disease-associated CV (1/6), and reversible arterial
      vasoconstriction (RAV) of the CNS (1 migraine, 1 eclampsia and 1 toxic
      encephalopathy) (3/6). In all patients with RAV MRA showed a complete remission
      of the vascular alterations after treatment. In the patients with isolated
      angiitis of the CNS and Crohn-disease-associated CV, partly regressive and partly
      progressive changes were demonstrated. The MR-angiographically detectable
      vascular alterations corresponded to the clinical course of the disease, as well
      as to TCD in all our patients. Success of therapeutic procedures, the need and
      the intensity of further drug administration could be estimated. The MRA appears
      to be a valuable non-invasive method in the follow-up of patients with CV and
      RAV.

PMID- 15257879
TI  - The effect of examination stress conditions on the cortisol content of saliva - a
      study of students from clinical semesters.
AB  - PURPOSE: Psychological stress factors can lead to changes in the immune system,
      the nervous system, and to psychosomatic diseases, besides releasing typical
      stress metabolites. This study on hand was to record the reliability of stress
      self assessment of students in various stress periods, and to be compared with
      the cortisol value of the saliva. MATERIALS AND METHODS: A total of 38 healthy
      students (18 women and 20 men), with an average age of 26.9 participated. The
      saliva of the participants was always tested between 9 AM and 10 AM, and always
      in various stress periods - during a typical semester internship, and immediately
      following the oral final examination. This was followed by a questionnaire
      concerning daily life styles (nutrition, part-time employment, sleeping pattern).
      The evaluation of the respective cortisol concentration of the total saliva
      resulted in a statistically high significant difference of values, relevant to
      stress levels (p = 0.0001). RESULTS: An average value for cortisol of 0.085
      microg/dl total saliva was measured in the non-stress period, and in the stress
      period of 0.315 microg/dl total saliva. The comparison of the questionnaire
      evaluation to life styles did not show anything significant, the comparison to
      the cortisol concentration of the saliva showed significant deviations from the
      individual stress assessments by the participants. CONCLUSION: The results cover
      a significant correlation of particular stress factors to changes in cortisol
      values. It is important for dental therapy to use stress reducing measures, or
      reduce them as much as possible in order to avoid factors that pre-operatively
      can affect the patient in a stressful way.

PMID- 15257880
TI  - Intensive care management of acute liver failure.
AB  - Acute liver failure represents one of the most challenging conditions in
      intensive care treatment. In most cases there is no causal medical therapy
      available for survive making the intensive care treatment as the most important
      management tool, as bridge to transplant or still the recovery of the liver!
      These patients frequently develop multi-organ failure, placing them at risk of
      hemodynamic disorder, cerebral edema, coagulopathy and various renal and
      metabolic complications.

PMID- 15257881
TI  - Cardiovascular risk factors and probability for cardiovascular events in HIV
      infected patients - part III: age differences.
AB  - OBJECTIVE: In recent years, concerns have been growing about an elevated rate of
      cardiovascular diseases in HIV-infected patients due to side effects of
      antiretroviral therapy. The present study analyses the cardiovascular risk
      profile and the probability of cardiovascular events with regard to the age of
      HIV-infected patients. METHODS: Cardiovascular risk factors of 309 HIV-infected
      adults were analysed. Patients were divided into four groups: 18-30 years (group
      1), 31-40 years (group 2), 41-50 years (group 3), > 50 years (group 4). Overall
      10-years probability for cardiovascular events was evaluated by the Framingham
      algorithm. RESULTS: Differences between the groups were detected in
      cardiovascular risk factors including changes in lipid- and glucose metabolism.
      Lipid values increased with elevated age, such as total cholesterol concentration
      (Mean +/- SEM in group 1 vs. group 4: 4.71 +/- 0.20 to 6.36 +/- 0.21 mmol/L, p <
      0.05), LDL-cholesterol concentration (2.86 +/- 0.17 vs. 4.17 +/- 0.21 mmol/L, p <
      0.05) and triglyceride concentration (1.56 +/- 0.14 vs. 3.48 +/- 0.40 mmol/L, p <
      0.05). HDL-cholesterol concentration did not show a significant difference (1.15
      +/- 0.03 mmol/L). Glucose concentration increased with elevated age in HIV
      infected patients (5.28 +/- 0.19 vs. 6.46 +/- 0.24 mmHg, p < 0.05), but there was
      no significant difference in HbA1c - concentration, blood pressure and smoking
      rate between the groups. The overall 10-years probability for cardiovascular
      events was higher in group 1 (median: 1.9%) than in group 4 (20.5%; p < 0.01).
      CONCLUSIONS: The risk of cardiovascular events is related to the age in HIV
      infected patients. Therefore, an increased duration of life due to a more
      effective antiretroviral therapy will have a significant impact on the rate of
      cardiovascular events in this patient population. In the future, further increase
      of cardiovascular events in HIV-infected patients may be expected.

PMID- 15257882
TI  - Primary drug-resistance in HIV-positive patients on initiation of first-line
      antiretroviral therapy in Germany.
AB  - BACKGROUND: Resistance against antiretroviral drugs in previously untreated HIV
      infected persons is of growing relevance. The aim of the study is to determine
      the prevalence of resistance-associated mutations in this patient group. METHODS:
      In a prospective multicenter-study in Nordrhein-Westfalen, Germany, genotypic
      resistance testing was performed in untreated HIV-positive patients before
      administration of first-line highly active antiretroviral therapy (HAART).
      RESULTS: Between January 2001 and August 2002 resistance testing was performed in
      184 therapy-naive individuals. HAART was initiated in 143 patients, who were
      included into the study. 70.6 % were males, mean age was 39 years, mean duration
      of diagnosis of HIV-infection was 1.5 years. The proportion of cases at CDC stage
      C was 45.4%, mean CD4-cell count was 199 /ml, mean viral load was 206,855
      copies/ml. Resistance-associated mutations were detected in 20 patients (14.0%).
      10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor-
      (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q),
      2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance
      (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated
      resistance (V82A, L90M), respectively. Multi-class-resistance was found in 2.1%,
      mutations indicating revertant variants of resistant strains were found in 4.2%
      (T215C/E/L/S). 86.7% of the isolates showed secondary mutations in the protease
      gene. No significant difference in the distribution of the parameters age, sex,
      duration of HIV diagnosis, CDC stage, CD4-cell count, and viral load, between
      groups with and without resistance was identified. CONCLUSION: The prevalence of
      primary resistant virus strains can be estimated at 14% in chronically infected
      HAART-naive HIV-patients in Germany. The majority of these cases show NRTI
      associated resistance. Resistance against NNRTI or PI as well as multi-class
      resistance is of low prevalence. No risk factor of predictive value can be
      identified for the diagnosis of resistance mutations in the individual. In
      conclusion, routine genotypic resistance testing in untreated HIV-positive
      patients should be performed before administration of first-line HAART in this
      region.

PMID- 15257883
TI  - Questionning aggravation of the headache during migraine attacks.
AB  - While questioning patients about aggravation of the headache by routine physical
      activity, sensitivity of walking stairs and lifting a heavy object versus head
      movements and bending down in terms of aggravating the headache was aimed to be
      determined. Eighty-one migraine patients were questioned about the aggravation of
      their headaches with two sets of question groups. (The first set: walking stairs
      and lifting a heavy object; The second set: rotating the head side to side and
      bending down). 38 and 72 patients gave clear answers to the first and second set
      of questions respectively. Clear information was obtained from the first and
      second group of questions by 38 and 72 patients respectively. Some patients with
      severe migraine headaches may prevent themselves from rigorous daily activities
      while they could bend or make sudden head movements inadvertently during the
      attack. We think that aggravation of the headache due to head movements or
      bending down during migraine attacks seems more sensitive than walking stairs or
      lifting a heavy object to migraine patients.

PMID- 15257884
TI  - Stroke following variceal sclerotherapy.
AB  - OBJECTIVE: Paradoxical embolism via a patent foramen ovale (PFO) has been
      identified as a potential risk factor for ischaemic stroke. Such occurrences are
      associated with risk factors for deep vein thrombosis (DVT), e. g. pregnancy,
      immobilisation, and surgery of the lower limbs. OBSERVATION: A 54-year-old
      otherwise healthy female presented with acute onset motoric aphasia and
      brachiofacial right hemiparesis. The cranial computed tomography showed a left
      striatal ischaemic infarction. The patient's history revealed a variceal
      sclerotherapy with polydocanol 0,5% three days prior to the onset of symptoms.
      Echovist TCM doppler revealed a right-to-left shunt. A patent foramen ovale (PFO)
      was detected by transesophageal echocardiography. There was no evidence of DVT in
      bilateral lower-extremity venous duplex ultrasound scanning. Other potential risk
      factors of stroke including thrombophilia could not be identified. The patient
      was treated with a high dose regimen of heparin and a further anticoagulation
      treatment was recommended. CONCLUSION: This case suggests a probable causal
      relationship between variceal sclerotherapy and paradoxical embolism resulting in
      a stroke. Variceal sclerotherapy might be a potential, but rare risk of embolism.

PMID- 15257885
TI  - Chronic headache: a focus on medication overuse.

PMID- 15257887
TI  - [Comparison of serum biochemistry between specific pathogen-free and conventional
      aged Wistar rats].
AB  - OBJECTIVE: To investigate the differences in serum biochemistry between specific
      pathogen-free (SPF) and conventional aged Wistar rats. METHODS: Coulter-JT
      Analyzer was used to measure the values of serum biochemistry in the two grades
      of rats. RESULTS: The serum levels of alanine aminotransferase (ALT), total
      protein (TP), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride
      (TG), blood urea nitrogen (BUN), creatinine, Fe, P, glucose, uric acid (UA), and
      low density lipoprotein (LDL) were very significantly different between male and
      female Wistar rats of either conventional or SPF grade (P<0.01), which also had
      significant difference in albumin, lactate dehydrogenase (LDH) and apolipoprotein
      B (ApoB) (P<0.05). Between male aged Wistar rats of the two grades, the
      differences of TP, albumin, albumin/globulin (A/G) ratio, TC, TG, blood glucose,
      ApoA1, ApoB, UA, high-density lipoprotein (HDL), LDL, and glutamic oxalacetic
      transaminase (GOT) were very significant (P<0.01), with also significant
      differences in ALT, Fe, Mg (P<0.05). Between the female rats of the two grades,
      the serum levels of ALT, TP, albumin, A/G ratio, ALP, TG, BUN, creatinine, Fe,
      ApoA1, APOB, HDL, LDL, and bile acids were very significantly different (P<0.01),
      and Mg was significantly different (P<0.05). CONCLUSION: Different
      microbiological profiles affect serum biochemistry of aged Wistar rats.

PMID- 15257886
TI  - [Clinical study of three-dose regimen of Zenapax in orthotopic liver
      transplantation].
AB  - OBJECTIVES: To observe the clinical efficacy and safety of three-dose regimen of
      Zenapax combined with tacrolimus (FK506), mycophenolate mofetil (MMF), and
      steroid in the early-stage management of liver transplantation. METHOD: Thirteen
      liver transplantation recipients received the same immunosuppression regimen with
      three-dose Zenapax combined with FK506, MMF, and steroid. The incidence of acute
      allograft rejection (AR), blood concentration and dosage of FK506, and the liver
      graft function were observed in the 30 days after liver transplantation and
      compared with the results documented in literatures. RESULTS: One patient
      developed AR 17 days after transplantation and 3 patients died on the
      postoperative days 14, 19 and 23, respectively, due to pulmonary fungal
      infection, acute hepatic failure or multiple organ failure resulting from
      stenosis and thrombosis of hepatic artery respectively. Ten recipients had
      various infections. An average of 16.56+/-10.40 d was taken for functional
      recovery of the liver graft, and the blood concentration of FK506 was maintained
      at (10.25+/-1.99)x10(-3) mg/L. Anaphylaxis, post-transplant lymphoproliferative
      disorder (PTLD), or other adverse effects were not observed. CONCLUSION: Three
      dose regimen of Zenapax in combination with FK506, MMF and steroid is safe and
      effective in the postoperative management of orthotopic liver transplantation.

PMID- 15257888
TI  - [Dedifferentiation and regeneration of damaged cells and tissues].
AB  - Dedifferentiation is an important event in developmental biology and morphology
      but frequently neglected by the biologists. In the past, attention was given
      predominantly to its relationship with tumorigenesis. In our series of
      researches, we found important and inherent relations between dedifferentiation
      and regeneration of damaged cells and tissues in the emergence of large numbers
      of Schwann cells that digested their own myelin sheath components and senescent
      organelles by autophagic mechanism during regeneration of the peripheral nerves
      following injuries, when some apocytosomes (apo+cyto+sis), by means of apocytosis
      (apo+cyto+sis), budded from the cells containing such primitive organelles as
      free ribosomes and polyribosomes and retaining a very small quantity of active
      mitochondria and Golgi apparatus, all characterizing an immature state of the
      cells after dedifferentiation. Many autophagic bodies were found enwrapped by
      membranes L02 cells (a liver cell line) after vincristine-induced damage, with
      numerous apocytosomes dissociated following budding around the cells. The cells
      survived the treatment presented immature appearance, a phenomenon we termed as
      dedifferentiation, after which the metabolic burden of the cells was relieved,
      the senescent and damaged organelles were cleared, and the cells resumed their
      viability and proliferated vigorously to repair and reconstruct the damaged
      tissues. As most researchers have currently give their full attention to the
      important role of stem cells in the regeneration of damaged cells and tissues,
      we, after long-term observations and experiments, propose that mature cells also
      take part in the regeneration and reconstruction process after dedifferentiation.

PMID- 15257889
TI  - [Isolation of the target gene from cDNA restriction fragments using 70-mer oligo
      microarray].
AB  - OBJECTIVE: To study the method for using a 70-mer oligo microarray as the probe
      to isolate target genes from the cDNA restriction fragments. METHOD: Samples of
      Saccharomyces cerevisiae mRNA was extracted after heat shock culture and
      reversely transcribed into the double-stranded cDNAs, which were prepared into
      restriction cDNA fragments using restriction display (RD) method. The microarray
      was printed using a single 70-mer specific oligo designed to according to the
      SSA1 gene of yeast. The cDNA restriction fragments were labeled by PCR method
      with the Cy5 universal primer before hybridization with the microarray. The
      microarray was stripped after washing and scanning, and the strip solution was
      collected for another round of PCR amplification using the universal primer
      without fluorescence. The PCR product was then cloned into PUC18 T vector and
      transformed into to E.coli JM109 cells for amplification, and the plasmids were
      extracted and sequenced for identification. RESULTS: BLAST results showed that
      the target gene was cloned successfully. CONCLUSION: The target gene can be
      isolated directly using the 70-mer oligo microarray as the probe from the cDNA
      fragments prepared by RD method, without the necessity of building a cDNA
      library. This method can also be used in further research to acquire the
      differentially expressed genes after the oligo microarray hybridization.

PMID- 15257890
TI  - [Differential screening of novel human metastasis-associated genes of colorectal
      carcinoma].
AB  - OBJECTIVE: To clone novel metastasis-associated genes of colorectal carcinoma and
      provide clues for the molecular mechanisms of metastasis of colorectal carcinoma.
      METHODS: By suppression subtractive hybridization (SSH), a pair of colorectal
      carcinoma cell lines with different metastatic potentials derived from the same
      parental cell line was used to construct two subtractive cDNA library specific
      for metastasis-accelerating genes or metastasis-suppressor genes. Partial
      positive clones in the two libraries were selected randomly and differentially
      screened, and the differentially expressed gene fragments obtained were sequenced
      and analyzed with BLAST software. The mRNA expressions of several new genes were
      confirmed by Northern blot analysis. RESULTS: Two subtractive cDNA libraries had
      235 and 232 white clones respectively and more than 90% of the white clones had
      the inserts. About 200 positive clones selected randomly were differentially
      screened, and 29 differentially expressed genes were obtained. Fifteen unknown
      genes were found by sequence and BLAST analysis and had been collected by the
      GenBank dbEST database with the entry number of CD485499 to CD485513, among which
      6 novel genes were located in the fifth chromosome. CONCLUSION: SSH is a reliable
      strategy for screening novel genes differentially expressed in metastasis of
      colorectal carcinoma. The fifth chromosome may harbor many new genes related with
      metastasis of colorectal carcinoma, and identified new genes can be cloned for
      their full length for further study of their functions.

PMID- 15257891
TI  - [C-reactive protein inhibits the expression of hypoxia-inducible factor-1alpha in
      human umbilical vein endothelial cells in hypoxic condition].
AB  - OBJECTIVE: To investigate the effect of C-reactive protein (CRP) on expression of
      hypoxia-inducible factor-1alpha (HIF-1alpha). METHODS: Using CoCl(2) (100
      micromol/L) to simulate hypoxic condition for culturing human umbilical vein
      endothelial cells (HUVECs), we examined the effects of CRP on expression of HIF
      1alpha. The proteins were extracted from the cells after a 24-hour exposure of
      the cells to CRP of varied concentrations in the presence of CoCl(2), and Western
      blotting was performed for quantification of HIF-1alpha expression, the results
      were analyzed statistically with SPSS software. RESULTS: CRP at the concentration
      of 5 microg/ml decreased the expression of HIF-1alpha (P<0.001), producing the
      maximum inhibitory effect at the concentration of 100 microg/ml, an effect
      exhibiting dose-dependence. CONCLUSION: CRP inhibits the expression of HIF-1alpha
      in HUVECs subjected to hypoxic condition, which serves as an important evidence
      for the inhibitory effect of CRP on angiogenesis in hypoxic condition.

PMID- 15257892
TI  - [Effects of Yizhi capsule, a preparation of traditional Chinese medicines, on
      delayed neuronal death in hippocampal CA1 region and memory function of rats
      after ischemia-reperfusion injury].
AB  - OBJECTIVE: To observe the effects of Yizhi capsule, a preparation of traditional
      Chinese drugs on delayed neuronal death in the hippocampal CA1 region and memory
      function of rats after ischemia-reperfusion injury. METHODS: Rat models of acute
      reperfusion injury after global cerebral ischemia were induced by vertebral and
      carotid arteries occlusion, and 1, 2, 4, 8 and 40 d after model establishment,
      the neurons in the rat hippocampal CA1 region were obtained and
      immunohistochemically stained for counting. Morris water maze test was performed
      to observe the learning and memory capacities of the rats 40 d after the injury.
      RESULTS: The number of normal neurons was significantly higher in the rats
      treated with Yizhi capsule (100 mg/kg.b.w.) than in those without the treatment,
      and the former group of rats used significantly shorter time in finding the
      platform under the water surface in Morris water maze test. CONCLUSION: Yizhi
      capsule may protect the neurons in the hippocampal CA1 region and improve on the
      learning and memory dysfunction after global ischemia/reperfusion injury in rats.

PMID- 15257893
TI  - [Effect of decidual cell conditioned media on invasion-related gene expression of
      ovarian tumor cell line COC1].
AB  - OBJECTIVE: To study the effect of decidual cell conditioned media (DCM) on the
      expression of the invasion-related gene of ovarian tumor cell line COC1. METHODS:
      After primary culture of the decidual cells of early and late pregnancy, DCM was
      extracted from the cell cultures for treatment of the ovarian tumor cell line
      COC1. Analysis of the invasion-related gene expression in COC1 cells was
      performed by way of reverse transcriptional (RT)-PCR. RESULTS: The COC1 expressed
      the mRNAs of matrix metalloproteinase 2 (MMP-2), tissue inhibitor of
      metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor type 1 (PAI-1),
      but not those of MMP-9, TIMP-1 or urokinase-type plasminogen activator (u-PA).
      The DCM of the early- and late-pregnancy decidual cell cultures significantly
      down-regulated the MMP-2 expression, and up-regulated the expression of the TIMP
      2 and PAI-1 mRNA in COC1 cells in comparison with the control cells (P<0.01).
      CONCLUSION: DCM can lower the invasive capacity of the ovarian tumor cell line
      COC1 by interrupting the balance between MMP-2 and TIMP-2 and between u-PA and
      PAI-1.

PMID- 15257894
TI  - [Reconstruction of the mandibular model using a three-dimensional laser scanner].
AB  - OBJECTIVE: To construct a three-dimensional (3D) mandibular model using a 3D
      laser scanner, and explore a new method for reconstructing the finite element
      geometry model. METHODS: A mandible specimen was scanned with the 3D laser
      scanner to form the point clouds of the mandibular surface, which were
      subsequently aligned for reconstruction of the mandibular model. RESULT: A 3D
      model of the mandible surface was reconstructed, which could be used for finite
      element simulation. CONCLUSION: The 3D laser scanning system can be used to
      reconstruct the 3D model with irregular geometry for finite element simulation.

PMID- 15257895
TI  - [Expressions of hTERT, p53, c-erbB-2 and Bcl-2 in colonic adenocarcinoma mouse
      models with liver metastases: effects of classical traditional Chinese medicine
      prescriptions for promoting circulation and removing blood stasis].
AB  - OBJECTIVE: To observe the effects of classical traditional Chinese medicine
      prescriptions that function to promote blood circulation and removing blood
      stasis on the metastatic behavior of malignant tumors, and explore the possible
      mechanisms of such effects. METHODS: BALB/c mouse models of colonic
      adenocarcinoma with liver metastases were established by intrasplenic injection
      of colonic adenocarcinoma cells (CT26) to receive treatment with the three
      representative classical circulation-promoting and blood stasis-removing
      prescriptions of traditional Chinese medicine, namely Guizhifuling pills, Didang
      Tang and Danshenyin, respectively. The expressions of human telomerase reverse
      transcriptase (hTERT), p53, c-erbB-2 and Bcl-2 were detected in the mouse models
      with different treatments and in normal control mice. RESULTS: Tumor metastases
      of various degrees were observed in the mice after inoculation of the tumor
      cells. The expressions of hTERT, p53, c-erbB-2 and Bcl-2 in the models receiving
      treatment with either Didang Tang or Guizhifuling pills differed significantly
      from those of the untreated model group (P<0.05), whereas between Danshenyin
      group and the model group, only the expression of hTERT showed significant
      difference. CONCLUSION: Didang Tang and Guizhifuling pills can reduce the
      expressions of hTERT, p53, c- erbB-2 and Bcl-2, while Danshenyin can only reduce
      the expression of hTERT without similar effects on the other 3 oncogenes. Such
      inhibitory effects of the prescriptions on hTERT and the oncogenes might explain
      their actions to inhibit malignant tumor metastasis, which can be related to
      performance of the prescriptions in promoting circulation by removing blood
      stasis.

PMID- 15257896
TI  - [Pathological changes of cat brain tissues after cranial gunshot wound in hot and
      humid environment].
AB  - OBJECTIVE: To investigate pathological changes in cat brain tissues after gunshot
      wound in the head in hot and humid environments. METHODS: Sixteen cats were
      randomly divided into 4 groups, namely the normal environment (group 1), gunshot
      in normal environment (group 2), hot and humid environment (group 3), and gunshot
      wound in hot and humid environment (group 4) groups. Pathological changes of the
      cat brain tissues were observed with both optical and electron microscopes.
      RESULTS: The early-stage changes in group 2 were high-lighted by vasomotor
      dysfunction, with the coexistence of both vascular spasm and dilation. In group
      3, vascular spasm was depressed while hemorrhagic changes increased. On the brain
      tissue sections in group 4 for optical microscopic observation and ultra-thin
      sections for electron microscopic examination, the number of viable neural cells
      was obviously reduced, and edema, degeneration of the organelle occurred;
      loosening of the capillary tight junction, rupture and bleeding of the blood
      vessels, as well as degeneration and loosening of the myelin sheath were observed
      by transmission and scanning electron microscopes, and such changes were more
      serious than those in group 2. CONCLUSION: The hot and humid environment can
      significantly affect the pathological changes in the brain tissues of cat with
      cranial gunshot wound.

PMID- 15257897
TI  - [Three-dimensional architecture and ultrastructure of the cerebral
      microvasculature of missile brain wound in cats].
AB  - OBJECTIVE: To explore the changes of cerebral microvasculature in cats with
      missile brain wound. METHODS: The microvascular corrosion casts of the brain were
      examined by scanning electron microscopy, and the ultra-thin slices of the brain
      were inspected by transmission electron microscopy. RESULTS: The brain
      microvasculature showed evidently abnormal morphological changes, with both
      vasospasm and vasodilation as well as concurrent bleeding and ischemia. Strong
      pathological contraction of vascular sphincter, rupture of some microvessels, and
      increased microvilli and vacuoles in the endothelial cells were observed.
      Loosening of the intercellular tight junction and basal membrane rupture occurred
      along with perivascular swelling and neural cell damages. CONCLUSION:
      Morphological or functional changes occur in the cerebral microvasculature
      leading to secondary brain injury after missile brain wound in cats.

PMID- 15257898
TI  - [Therapeutic effects of chemotherapeutic regimen with pirarubicin for adult high
      risk acute leukemia].
AB  - OBJECTIVE: To evaluate the therapeutic effects of chemotherapeutic regimen with
      pirarubicin in the management of adult high-risk acute leukemia. METHODS: Twenty
      nine high-risk acute leukemia patients were selected as the treatment group and
      another 29 patients with similar pretreatment conditions as the control group. In
      the treatment group, 18 patients had acute non-lymphocytic leukemia (ANLL), and 8
      had acute lymphocytic leukemia (ALL) and 3 had mixed leukemia, all received
      treatment regimens with pirarubicin+cytarabine,
      vincristine+pirarubicin+prednisone, Vincristine+pirarubicin+L-asparaginase
      (L)+prednisone or pirarubicin+cytarabine+vincristine+prednisone. Routine
      therapeutic regimens were adopted in the management of the control. RESULTS: In
      ANLL patients, the overall remission rate was significantly higher in the
      treatment group than in the control group (77.78% vs 44.44%, P=0.031). Patients
      in the treatment group had greater marrow suppression and higher incidence of
      infections than the control group (P=0.012). CONCLUSION: Regimens with
      pirarubicin is more effective than the routine regimens in the management of
      patients with high-risk ANLL and produce greater but tolerable marrow
      suppression.

PMID- 15257899
TI  - [Detection of human telomerase reverse transcriptase mRNA of cells in pleural
      fluid by two-step in situ hybridization using digoxin-labeled oligonucleotide
      probes].
AB  - OBJECTIVE: To establish an method for detecting human telomerase reverse
      transcriptase (hTERT) mRNA of cells in pleural fluid by in situ hybridization
      (ISH), and to evaluate preliminarily the efficacy of this new method in
      recognizing neoplastic cells in the pleural fluid. METHODS: Fresh pleural fluid
      specimens were collected in 23 patients with pleural effusions and cell smears
      were prepared and after pretreatment, ISH between hTERT mRNA of the cells and
      digoxin-labelled oligonucleotide probes was performed. The signals of hTERT mRNA
      were detected by the sequential treatment with antigen, antibody, enzyme, and
      staining. With strict negative and positive controls, the experimental study was
      performed independent of clinical diagnosis and treatment. RESULTS: Positive
      results were seen in 9 cases of malignant pleural effusions, where dark staining
      of the cytoplasm and a few stained spots in the cell nuclei could be observed
      microscopically irrespective of the cytomorphological findings. Seven of the 9
      cases had positive results of cytomorphological examination, in which neoplasmic
      cell with obvious morphological abnormalities were also spotted. In the other 2
      cases where cytomorphological findings were negative but pleural biopsy confirmed
      the diagnosis of malignant pleural effusions, cytoplasm dark staining with
      stained spots in the cell nuclei were seen under microscope in spite of the
      absence of obvious abnormality in cell morphology. In contrast, the 14 cases with
      benign pleural effusions all had negative results, in which neither staining of
      the cells was identified microscopically, nor was evidently abnormal cell
      morphology. CONCLUSIONS: As a new method of clinical cytopathology, detection of
      hTERT mRNA of cells in the pleural fluid by ISH may provide a new means for
      cytomorphological examination for differential diagnosis between benign and
      malignant pleural effusions and for classification of the identified tumor cells.

PMID- 15257900
TI  - [Effect of XK469 and adriamycin on the growth of H460 cells in vitro and its
      mechanism].
AB  - OBJECTIVE: To investigate the inhibitory effect of XK469 on the in vitro growth
      of H460 cells and its mechanism. METHODS: The survival curves of H460 cells
      treated with XK469, XN472 and adriamycin, respectively, were obtained by MTT
      analysis, and the effect of XK469 and adriamycin on the cell cycle of H460 cells
      examined by flow cytometry. Western blotting was adopted for detecting the
      expression of cdc2 and phos-cdc2 induced by XK469 and adriamycin. RESULTS:
      Different concentrations of XK469 and adriamycin could significantly inhibit the
      growth of H460 cells, induce their G2/M phase arrest, and increase phos-cdc2
      expression; XN472 had a lesser effect on the growth of H460 cells. CONCLUSION:
      XK469 can increase phos-cdc2 expression and induce G2/M phase cell cycle arrest
      of H460 cells, resulting in inhibition of H460 cell growth. The inhibitory effect
      of XK469 on H460 cell growth is attributed to the chlorine in the 7-positon of
      its structure.

PMID- 15257901
TI  - [Expression of glucosylceramide synthase mRNA in vincristine-resistant KBV200
      cell line in association with multidrug resistance].
AB  - OBJECTIVE: To investigate the relationship between the expression of
      glucosylceramide synthase (GCS) mRNA in vincristine-resistant KBV(200) human
      cancer cell line and multidrug resistance (MDR) of the cancer cells. METHODS:
      Reverse transcriptional polymerase chain reaction (RT-PCR) was employed to
      analyze the differential expression of GCS mRNA between KBV(200) and KB cell
      lines and the changes in the mRNA expressions of GCS and mdr1 gene in KBV(200)
      cells after reversion of MDR. The effects of de-phenyl-z-palmaitoylamino-3
      morpholine-1-propanol (DL-PPMP) and verapamil in reversing MDR of the cells were
      evaluated by MTT assay. RESULTS: KBV(200) cells exhibited significantly increased
      expressions of GCS and mdr1 gene, whereas mdr1 gene failed to be detected in the
      parental KB cells. DL-PPMP within the concentrations ranging from 5 to 25
      micromol/L could inhibit the expression of GCS gene, with the maximum inhibition
      achieved at 25 micromol/L. Verapamil at the concentration of 10 micromol/L was
      already sufficient to induce inhibition of GCS expression in KVB(200) cells,
      which was more manifest with the concentration of 15 micromol/L. DL-PPMP and
      verapamil were found to inhibit mdr1 gene expression in KBV(200) cells at the
      mRNA level, and complete inhibition occurred after a 48-hour DL-PPMP treatment at
      25 micromol/L. CONCLUSION: The inhibition of GCS and mdr1 gene expressions is
      positively correlated with the concentrations of DL-PPMP and verapamil, which can
      reverse MDR by inhibiting synthesis of GCS and mdr1 gene, indicating the positive
      correlation between the expression of GCS gene and MDR in KBV(200) cells. GCS
      gene might play an important role in MDR during tumor progression.

PMID- 15257902
TI  - [Preparation and characterization of podophyllotoxin
      dipalmitoylphosphatidylcholine proliposome].
AB  - OBJECTIVE: To prepare podophyllotoxin-dipalmitoylphosphatidylcholine (PPT-DPPC)
      proliposomes (PPT-DPPC-PL) for improvement of the stability of PPT-DPPC liposome.
      METHODS: Freeze-drying method was used to prepare PPT-DPPC-PL, and the particle
      morphology, size range, encapsulation efficiency and stability of PPT-DPPC
      liposome were investigated. RESULTS: After hydration of PPT-DPPC-PL, PPT-DPPC
      liposome appeared multivesicular under electron microscope and the particles were
      distributed homogeneously with an average particle size of 1.45+/-0.38 microm.
      The encapsulation efficiency of PPT was 72.3%, and after storage at 4 to 40
      degrees Celsius; for 1 to 6 months, the proliposome remained stable. CONCLUSION:
      The prepared PPT-DPPC-PL particles by freeze-drying method are evenly
      distributed. The preparation method is relatively simple with higher embedding
      ratio and better stability.

PMID- 15257903
TI  - [Influence of liver lesions and vitamin K1 on bleeding after liver biopsy in
      patients with chronic renal failure].
AB  - OBJECTIVE: To investigate the influence of liver lesions and vitamin K1 on
      bleeding after liver biopsy in patients with chronic renal failure and hepatitis
      virus infection. METHODS: Ninety-two renal transplant recipients on hemodialysis
      with hepatitis B or C virus infection received percutaneous liver biopsy. The
      severities of liver inflammation and fibrosis were evaluated by semi-quantitative
      technique. Thirty-four patients were given intramuscular injection of vitamin K1
      before liver biopsy at the dose of 10 mg twice daily for 3 days. RESULTS: The
      total incidence of bleeding after liver biopsy was 12.0% (11/92) in these
      patients, and the use of vitamin K1 did not significantly influence the incidence
      of bleeding, nor did the degree of liver lesions. CONCLUSIONS: Bleeding occurred
      with a relatively high incidence after liver biopsy in patients with chronic
      renal failure and hepatitis virus B or C infection; vitamin K1 before liver
      biopsy could not reduce the incidence of bleeding, which is not correlated with
      the degree of liver lesions.

PMID- 15257904
TI  - [Immunological reaction between the peptides from S1 domain of SARS coronavirus S
      protein and the serum from SARS patients].
AB  - OBJECTIVE: To examine the immunological reactions between the peptides of SARS
      coronavirus (SARS-Cov) S-protein and the serum of SARS patients for identifying
      the SARS-Cov epitope. METHODS: The peptides from S1 domain of SARS-Cov S-protein
      were synthesized by peptide synthesizer, and the immunological reaction of the
      peptides with the serum of SARS patients were examined by means of ELISA.
      RESULTS: The optical density value of the immunological reaction of synthesized 8
      peptides with SARS patient serum was 1.5-2.6 times higher than that with normal
      serum. CONCLUSION: The 8 peptides from S1 domain of S protein appear to have low
      immunogenicity to the serum of SARS patients, indicating that these peptides may
      not be the epitope of the SARS-Cov.

PMID- 15257905
TI  - [Determination of serum highly sensitive C-reactive protein in patients with type
      2 diabetes].
AB  - OBJECTIVE: To investigate the relationship between serum level of highly
      sensitive C-reactive protein (hs-CRP) and insulin sensitivity in type 2 diabetic
      patients. METHODS: Serum hs-CRP level was determined by highly sensitive enzyme
      linked immunosorbent assay (ELISA) in 65 patients with type 2 diabetes and 25
      normal controls. Plasma glucose, serum insulin, glycosylated hemoglobin (HbA1c),
      urinary albumin excretion rate (UAER), plasma lipids and lipoprotein were also
      measured. Moreover, homeostasis model analysis (HOMA) of insulin resistance index
      (HOMA-IR) and islet secretion index (HOMA-IS) were calculated to estimate the
      insulin sensitivity and islet function. RESULTS: In the patients with type 2
      diabetes, serum hs-CRP was increased, HOMA-IR index and HOMA-IS index were
      decreased as compared with the normal control subjects (P<0.01). Moreover, serum
      hs-CRP was significantly higher in poorly controlled diabetic patients (n=23)
      with HbA1c >7% than that in well controlled diabetic patients (n=42) with
      HbA1c<7%. Liner regression analysis in diabetic patients showed that serum hs-CRP
      was negatively correlated with HOMA-IS index but positively correlated with
      fasting plasma glucose, body mass index, HbA1c and diastolic blood pressure,
      respectively. CONCLUSION: Serum HS-CRP level is higher in the patients with type
      2 diabetes than in normal subjects, and plays an role in the development and
      progression of type 2 diabetes mellitus.

PMID- 15257906
TI  - [Vascular endothelial growth factor gene transfection and survival of the random
      skin flap in rats].
AB  - OBJECTIVE: To investigate the effects of vascular endothelial growth factor
      (VEGF) gene transfection on survival of the random skin flap in rats. METHOD:
      Thirty SD rats were randomized equally into 3 groups: pcDNA3-VEGF165, pcDNA3 and
      control groups, with the former two groups transfected via liposome with pcDNA3
      VEGF165 and pcDNA3 respectively 48 h before and during the operation. Ischemic
      random skin flaps ( 1 cmx7 cm) were constructed from the rats. Seven days later,
      the amount of viable tissue within the flap was measured by planimetry. After the
      animals were killed, and specimens from the random skin flaps were harvested for
      immunohistologic evidence of VEGF protein expression and for HE staining to
      examine the microvascular growth. RESULTS: The results of tissue survival
      planimetry of the skin flap of pcDNA3-VEGF165, pcDNA3 and control groups were
      48.46% +/-3.35%, 30.20%+/-2.16%, and 31.35% +/-1.99%, which were highest in the
      VEGF- transfected group (P<0.05), in which immunohistochemical staining revealed
      increased deposition of VEGF in comparison with the other control groups   P<0.05
      . The VEGF group had also higher average vessel number as compared with the
      vector and control group (107.72+/-9.42 vs 91.35+/-7.28 and 89.85+/-7.66,
      P<0.05), and smaller average vessel lumen diameter (25.76+/-3.23 microm vs
      32.12+/-1.58 microm and 33.49+/-2.29 microm, P<0.05). CONCLUSION: pcDNA3-VEGF165
      transfection may enhance the survival of the ischemic skin flaps and achieve VEGF
      expression in the flaps in rats.

PMID- 15257907
TI  - [Mining gene expression microarray data of nasopharyngeal carcinoma by literature
      profiling].
AB  - OBJECTIVE: To study abnormal signal pathway in nasopharyngeal carcinoma (NPC).
      METHOD: NPC gene expression microarray data was mined by analysis of literature
      profiles generated by extracting the frequencies of certain terms from the
      abstracts stored in the Medline literature database. The terms were then filtered
      on the basis of both repetitive occurrence and co-occurrence among multiple gene
      entries. Finally, clustering analysis was performed on the retained frequency
      values, shaping a coherent picture of the functional relationship among large and
      heterogeneous lists of genes. RESULT: Sixteen function groups were found among
      112 abnormally expressed genes, including 4 groups indicative of Epstein-Barr
      virus (EBV) infection, 6 groups indicative of normal nasopharyngeal tissues that
      acquired essential capabilities to develop into tumor, 2 groups involved in
      energy metabolism, 1 group suggesting abnormal phosphorylation of proteins, 2
      groups related to other diseases, and 1 group associated with muscle activities.
      The pathways of p53 and Rb, which were frequently abnormal during tumor
      progression, were not found in these groups. CONCLUSION: Initiation and
      progression of NPC may be caused by special signal transduction pathways.

PMID- 15257908
TI  - [Ultrafiltration with different membranes and respiratory function after
      cardiopulmonary bypass].
AB  - OBJECTIVE: To investigate the protective effect of ultrafiltration on pulmonary
      function after cardiopulmonary bypass (CPB) by comparing two different membranes
      used in the ultrafiltration. METHODS: Thirty patients undergoing cardiac surgery
      with CPB were randomly divided into adsorption group (n=15) and control group
      (n=15), and in the former group, AN69 membrane was used for ultra-infiltration,
      with polysulfone (PS) membrane adopted in the control group during CPB. Plateau
      airway pressure (P(Plateau)), peak airway pressure (P(Peak)), static pulmonary
      compliance (Cst), dynamic pulmonary compliance (Cdyn) and respiratory index (RI)
      were measured or calculated before and 5, 60, 120, and 240 min after CPB in each
      group respectively. RESULTS: During the period of 5 to 240 min after CPB, the
      increase in P(Plateau), P(Peak), RI and decrease in Cst and Cdyn were much more
      obvious and lasted for longer time in the adsorption group than in the control
      group (P<0.05). No operative death or hemoglobinuria occurred in these cases.
      CONCLUSION: Ultrafiltration with AN69 membrane more effectively reduces CPB
      induced lung injury and improves the postoperative respiratory function than with
      PS membrane.

PMID- 15257909
TI  - [Subcloning of human neurotrophin-3 gene and construction of its genetically
      engineered cell model].
AB  - OBJECTIVE: To subclone human neurotrophin-3 gene (NT3) and transfer this gene
      into human bone marrow mesenchymal stem cells (BM-MSCs) to construct genetically
      engineered cells that produce NT3 in vitro. METHODS: Human BM-MSCs were cultured
      in low-glucose DMEM supplemented with 10% fetal bovine serum and 10 ng/ml
      epidermal growth factor. Flow cytometry (FCM) was used to examine the phenotypes
      of the cells. The eukaryotic expression vector pcDNA3.1(+)/NT3 was constructed
      and transferred into human BM-MSCs in vitro via liposomes. The genetically
      engineered BM-MSCs were selected several times with G418 and the clones were
      obtained and then amplified, followed by extraction of the RNA for detection of
      NT3 gene expression by reverse transcriptional (RT) PCR. The biological activity
      of the genetically engineered cells was examined by the collecting the
      supernatant of the culture medium for incubation of guinea pig cochlea hair
      cells. RESULTS: The cultured cells expressed CD13, CD29 and CD59, but no7 CD11,
      CD14, CD31, CD34, CD45, CD80, CD86, CD117 or HLA-DR. The BM-MSCs genetically
      modified with pcDNA3.1(+)/NT3 not only expressed and produced NT3, but also
      promoted the survival of the guinea pig cochlea hair cells in vitro. CONCLUSION:
      It is possible to construct the genetically engineered BM-MSCs that excrete NT3
      in vitro.

PMID- 15257910
TI  - [The first polar body of human oocytes does not help predict the precise location
      of the spindle].
AB  - OBJECTIVE: To observe the precise position of the metaphase II spindle for
      facilitating clinical practice of assisted reproduction. METHODS: LC-PolScope
      imaging system was used for observing the spindles in human metaphase II oocytes
      matured in vitro or in vivo, and the angle between the center of the oocyte, the
      spindle and the first polar body was measured and compared between in vitro and
      in vivo matured oocytes. RESULTS: In vitro and in vivo matured oocytes were
      significantly different in the angle between the spindle and the first polar body
      (P=0.006). CONCLUSION: The deviation of the spindle from the polar body in in
      vitro matured oocyte was significantly smaller than that in in vivo matured
      oocyte, and the first polar body does not help predict the precise location of
      the metaphase II spindle. The imaging system is safe and effective for observing
      the spindles.

PMID- 15257911
TI  - [Diagnosis of osseous metastases of malignant tumors by bone scanning combined
      with bone alkaline phosphatase detection].
AB  - OBJECTIVE: To assess the diagnostic value of bone alkaline phosphatase (B-AKP)
      detection in diagnosis of osseous metastases of malignant tumors. METHODS: Bone
      scanning and B-AKP detection were performed in 106 patients with malignancies.
      According to the findings in bone imaging and clinical symptoms, the patients
      were divided into bone metastases group (BM) and non-bone metastases group (NBM),
      between whom B-AKP was compared by t test. According to the number of osseous
      lesions on bone imaging, the patients were graded and B-AKP was compared between
      the 4 grades. Correlation analysis was performed between B-AKP level and the
      number of osseous lesions. RESULTS: Among the 106 patients, bone scanning found
      osseous metastases in 68 patients. For diagnosing osseous metastases, the
      sensitivity, specificity, PPV and NPV of B-AKP detection were 89.7%, 52.6%, 77.2%
      and 74.0%, respectively. B-AKP was 28.4+/-14.8 microg/L in BM group and 12.8+/
      7.6 microg/L in NBM group, showing significant difference (t=6.056, P<0.001). B
      AKP was 13.9+/-6.8 microg/L, 17.2+/-9.4 microg/L, 23.8+/-10.4 microg/L and 49.5+/
      17.6 microg/L in patients of grade 0, 1, 2, and 3, respectively, showing
      significant difference by comparisons between the grades (P<0.05) except for that
      between grades 0 and 1 (t=1.320, P>0.05) and between grades 1 and 2 (t=1.803,
      P>0.05). B-AKP was 19.6+/-4.2 microg/L in patients with single hot focus and
      13.1+/-3.4 microg/L in patients with single cold focus (t=2.570, P<0.05).
      Correlation analysis showed that there was low-degree correlation between B-AKP
      level and the number of osseous lesions (r=0.751, P<0.01). CONCLUSIONS: B-AKP
      level detection and bone imaging yield consistent results. For diagnosis of
      osseous metastases in patients with malignant tumor, bone scanning is the primary
      choice but in cases of single hot lesions, B-AKP should be performed to prevent
      missed diagnosis; for false positive lesions, B-AKP should also be detected to
      prevent misdiagnosis.

PMID- 15257912
TI  - [A simple method for evaluation of the stability of magnetic resonance scanner
      during brain function imaging].
AB  - OBJECTIVE: To develop a simple method for evaluating the stability of magnetic
      resonance (MR) scanner during brain function imaging. METHOD: A symmetrical water
      phantom was scanned using the same sequence and parameters as for brain function
      imaging. The stability of MR scanner was evaluated in view of the signal levels
      of phantom images. RESULT: The quality control chart of the mean value, standard
      deviation and the range of the signal level in the region of interest (ROI)
      within the same region on 128 phantom images were obtained, demonstrating the
      state of stability of the MR scanner. CONCLUSION: The quality control chart of
      ROI can be used to evaluate the stability of the MR scanner.

PMID- 15257913
TI  - [Prognostic value of changes of peripheral blood T cell subsets after
      thermoradiotherapy for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To assess the prognostic value of changes of peripheral blood T cell
      subsets after thermoradiotherapy for nasopharyngeal carcinoma (NPC). METHODS:
      Peripheral blood T cell subsets in 20 normal subjects (control group), 30 NPC
      patients undergoing thermoradiotherapy, and 20 NPC patients undergoing
      radiotherapy were detected by flow cytometry. RESULTS: The percentages of
      CD3+CD4+ and CD8+CD28+ cells were decreased and the percentages of CD3+CD8+ and
      CD8+CD28- cells increased as compared with the measurements in normal persons.
      One month after thermoradiotherapy, the percentages of CD3+CD4+ and CD8+CD28+
      cells further decreased and the percentages of CD3+CD8+ and CD8+CD28- cells
      further increased, which continued to worsen 3 months after the treatment and
      appeared to be related to the survival of the patients. CONCLUSION: T cell
      subsets of NPC patients are abnormal and their immune functions depressed in NPC
      patients within a long period after thermoradiotherapy. CD8+CD28+ and CD8+CD28- T
      cell subsets can be significant for prognostic assessment in these patients after
      thermoradiotherapy.

PMID- 15257914
TI  - [Medroxyprogesterone acetate therapy against antiangiogenesis of transplanted
      ovarian cancer in nude mice].
AB  - OBJECTIVE: To investigate the effects of medroxyprogesterone acetate (MPA) on
      angiogenesis and growth of transplanted human ovarian cancer cells in nude mice.
      METHODS: Ovarian cancer cell line COCI derived from human ovarian serous
      adenocarcinoma was transplanted into 30 nude mice, which were then randomized
      equally into 3 groups consisting of two treatment groups (in which MPA was
      administered at 60 and 120 mg/kg, respectively, twice a week for 4 weeks) and a
      control group. Six weeks later, the body mass of the nude mice was recorded and
      the morphology of tumor cells observed by electron microscope. The microvascular
      density (MVD) was examined by immunohistochemical staining with anti-human factor
      VIII antibody. RESULTS: Compared with the control group, the growth inhibitory
      rate in the two treatment groups were 23.76% and 43.80%, respectively,
      corresponding to the doses of 60 and 120 mg/kg. MVD of 60 mg/kg MPA group (3.64+/
      0.02) and 120 mg/kg MPA group (2.11+/-0.12) was lower than that of the control
      group (5.14+/-0.74) (P<0.05 and P<0.01, respectively), and there was also
      significant difference between the two treatment groups (P<0.01). The
      morphological changes including compaction and margination of the nuclear
      chromatin, apoptotic bodies, and cell necrosis were significantly increased in
      the two treatment groups. CONCLUSIONS: MPA can inhibit the angiogenesis and
      growth of transplanted human ovarian cancer cells in nude mice in a dose
      dependent manner, and its anticancer effect may involve induction of cell
      apoptosis as the result of its effect against angiogenesis.

PMID- 15257915
TI  - [Automatic segmentation of brain tissue images based on mathematic morphology].
AB  - Mathematic morphological operators are used to segment automatically and
      appropriately the brain magnetic resonance (MR) images, and segmented regions for
      sequential MR images are reconstructed in three dimensions to help clinical
      analysis of the images.

PMID- 15257916
TI  - [Effects of captopril on myocardial tissue energy metabolism and inflammation in
      rats with diabetic cardiomyopathy].
AB  - OBJECTIVE: To study the protective mechanism of captopril in diabetic
      cardiomyopathy by means of DNA microarray. METHODS: Rat models of diabetic
      cardiomyopathy were divided into test and control groups (n=5), and the rats in
      the test group were given oral captopril (1.5 mg/kg  b.w.) for 15 weeks. DNA
      microarray was prepared by blotting the PCR products of 4 000 rat cDNAs onto a
      specially treated glass slides. The probes were prepared by labeling the mRNA
      from the myocardial tissue of both control and test groups with Cy3-d UTP and Cy5
      d UTP separately through reverse transcription. The arrays were then hybridized
      against the cDNA probes and the fluorescent signals scanned. RESULTS: The
      expression of genes in relation to fatty acid b oxidation, mitochondrial proton
      electron coupling and oxidative phosphorylation, and that of dithiolethione
      inducible gene-1 were up-regulated, while the dimethylarginine
      dimethylaminohydrolase gene expression was obviously lowered in the test group in
      comparison with those of the control group. CONCLUSION: Captopril may protect the
      myocardial tissue through improving myocardial energy supply and depressing
      inflammatory reaction.

PMID- 15257917
TI  - [Mifepristone combined with methotrexate for conservative treatment of tubal
      ectopic pregnancy].
AB  - OBJECTIVE: To observe the effects of mifepristone combined with methotrexate for
      conservative treatment of tubal ectopic pregnancy. METHODS: A total of 102 cases
      of tubal ectopic pregnancy diagnosed at early stage were enrolled to receive oral
      mefepristone at the dose of 75 mg twice daily for 3 d and intramuscular injection
      with calcium leucovorin at 0.1 mg/kg 24 h after a single dose of methotrexate
      injection (1 mg/kg.b.w.). In the control group consisting of 86 similar cases,
      intramuscular injection with calcium leucovorin at 0.1 mg/kg was given 24 h after
      a single dose of methotrexate (1 mg/kg.b.w.). RESULTS: Ninety-four of the 102
      cases ( 92.20%) receiving oral mifepristone combined with calcium leucovorin and
      methotrexate were cured, a curative rate significantly higher than that in the
      control group, where 70 cases (81.4%) were cured (P<0.05). CONCLUSION:
      Mefepristone combined with methotrexate is safe and effective in the treatment of
      tubal ectopic pregnancy, without obvious side effects.

PMID- 15257918
TI  - [Preparation of a composite membrane with collagen scaffold material for tissue
      culture].
AB  - OBJECTIVE: To prepare a composite membrane with collagen scaffold material for
      tissue culture. METHODS: Pure collagen membrane, collagen/hyaluronic acid (HA)
      membrane, collagen/chitosan membrane and collagen/chitosan/ HA membrane
      (abbreviated as composite collagen membrane) were prepared respectively, and
      their respective biodegradation time and the number of the cells proliferated on
      them were examined in vitro. RESULT: The biodegradation time of pure collagen,
      collagen/HA and composite collagen membranes in vitro was 1 380, 1 376 and 1 560
      min respectively, and the number of cells proliferated on the collagen/HA
      membrane and the composite collagen membrane were greater than that on the pure
      collagen membrane. CONCLUSIONS: Addition of chitosan can decrease the
      biodegradation of the collagen membrane in vitro, while HA can not; HA Can
      contribute to cell adhesion and proliferation on the collagen membranes, but
      chitosan does not.

PMID- 15257919
TI  - [Clinical analysis of acute coronary infarction patients with roughly normal
      coronary arteriographic findings].
AB  - OBJECTIVE: To investigate the detection rate and possible causes of acute
      coronary infarction (AMI) patients with roughly normal coronary arteriographic
      (CAG) findings. METHOD: A retrospective analysis was conducted in 311 cases of
      AMI undergoing CAG examination. RESULT: Of these 311 patients, 16 patients, whose
      age averaged 47.6 years, had roughly normal findings in CAG, including 9 below
      the age of 45 years, 10 with smoking history, and 5 with successful thrombolysis.
      CONCLUSION: Patients with normal or roughly normal CAG finding might also have
      AMI likely induced by coronary artery thrombosis and spasm.

PMID- 15257920
TI  - [Purification, identification of acoagulatin, an anticoagulation factor from the
      venom of Chinese Agkistrodon, and observation of its anticoagulation effect].
AB  - OBJECTIVE: To isolate and identify an anticoagulation factor, acoagulatin, from
      the venom of Chinese Agkistrodon and to observe its anticoagulation effect.
      METHOD: The venom of Chinese Agkistrodon was isolated and purified using ion
      exchange chromatography on DEAE-Sepharose Fast Flow and CM-sepharose Fast Flow.
      High-performance liquid chromatography (HPLC) was performed for determination of
      the purity of acoagulatin, and SDS-PAGE electrophoresis (with 5% concentrated gel
      of pH 6.8, 12% separation gel of pH 8.8, Tris-aminoacetic acid buffer of pH 8.3
      as the electrode buffer) for determining the relative molecular mass. For
      observation of the anticoagulation effect, 20 microl acoagulatin solution at the
      concentration of 0.30, 0.20 and 0.15 microg/microl, respectively, was mixed with
      100 microl rabbit anticoagulated plasma and the thrombin time (TT), prothrombin
      time (PT) and activated partial thromboplastin time (APTT) were determined.
      RESULTS: Acoagulatin was found to consist of two subunits with relative molecular
      mass of 14 400 and 17 000 respectively, resulting in the total relative molecular
      mass of 31 400 as determined by SDS-PAGE. HPLC demonstrated good homogeneity of
      this protein, which significantly prolonged the PT and APTT without affecting TT.
      CONCLUSION: DEAE-Sepharose Fast Flow and CM-sepharose Fast Flow ion exchange
      column chromatographies are effective to isolate acoagulatin of high purity,
      which possesses anticoagulation effect.

PMID- 15257921
TI  - [Determination of dexamethasone sodium phosphate content in Fuyankang cream by
      high-performance capillary electrophoresis].
AB  - OBJECTIVE: To determine the content of dexamethasone sodium phosphate in
      Fuyankang cream, a preparation for treatment of various skin conditions. METHODS:
      Dexamethasone sodium phosphate content in Fuyankang cream was determined using
      high-performance capillary electrophoresis (HPCE) at the detection wavelength of
      254 nm, under the optimal condition achieved with a fused-silica capillary tube
      (60 cm x 75 microm) and 100 mmol/L sodium tetraborate buffer (pH 9.2) at a
      constant voltage of 25 kV with a sampling time of 10 s at 25 degrees Celsius;.
      RESULTS: The calibration curve displayed good linear relationship within
      dexamethasone sodium phosphate concentration range of 20 to 100 microg/ ml
      r=0.999 8 . The average recovery of dexamethasone sodium phosphate was 99.75%
      n=5, RSD=1.03% . CONCLUSION: HPCE is simple, quick and sensitive in determination
      of dexamethasone sodium phosphate content in Fuyankang cream.

PMID- 15257922
TI  - [Hyperfractionated radiation therapy combined with concomitant chemotherapy for
      inoperable stage III non-small cell lung cancer: clinical analysis of 70 cases].
AB  - OBJECTIVE: To evaluate the effect of hyperfractionated radiation therapy and
      concomitant chemotherapy for inoperable stage III non-small cell lung cancer
      (NSCLC). METHODS: Seventy patients were randomized equally into two group. The
      therapy group received radiotherapy with hyperfractionated radiation therapy
      combined with concomitant chemotherapy, and the control group was treated with
      chemotherapy only. RESULT: The overall response rate, including the rate of both
      complete (CR) and partial responses (PR), in the therapy group was 60.0% with a
      CR rate of 8.6%. The overall response rate in the control group was 40.0% with a
      CR rate of 5.7%. The difference in overall response rate was statistically
      significant between the two groups (P<0.05). The median survival time, 1- and 2
      years survival rate were 12.8 months, 48.6%, and 25.7%, respectively, in the
      hyperfractionated radiotherapy group, and 9.4 months, 34.3%, and 17.1%,
      respectively, in the chemotherapeutic group (P 0.031). The major toxic effects of
      the chemotherapy were myelosuppression and radiation esophagitis. CONCLUSION:
      Hyperfractionated radiation therapy plus concomitant chemotherapy with paclitaxel
      for inoperable stage III NSCLC improves the short-term response of the patients,
      but fail to raise the survival rate.

PMID- 15257923
TI  - [Radiofrequency ablation of idiopathic right ventricular tachycardia].
AB  - OBJECTIVE: To study the effect of electrophysiological characterization and
      radiofrequency ablation on idiopathic right ventricular tachycardia. METHODS:
      Five patients ( 3 male and 2 female ) with an average age of 35.2+/-11.2 years
      were enrolled in this study. 7F EPT electrode in temperature-controlled mode was
      used for the ablation. The temperature and power were controlled within the range
      of 50-55 degrees Celsius; and 30-35 W respectively. The ablation target was the
      point that evidently induced P-potential at posterior right ventricular septum by
      scaling test. Tachycardia was stopped within 3 s. Consolidated discharge was
      within 40 s. The ablation was ended when the tachycardia could not be evoked
      during routine intracardiac electrophysiology test. Aspirin (0.1 g/d) was given
      orally for 1 month after operation. RESULTS: The body surface electrocardiogram
      did not change significantly after ablation. Neither S1S1 and program med
      stimulation, nor intravenous drip of isoproterenol after operation evoked
      tachycardia. Neither tachycardia nor complication appeared 4-6 months after the
      test. CONCLUSIONS: (1) Posterior right interventricular septum can also give rise
      to idiopathic ventricular tachycardia similar to left posterior interventricular
      septum. Ablation at the point where P-potential can be evidently induced by
      scaling test could easily acquire success. (2) Idiopathic right ventricular
      tachycardia has typical body surface electrocardiogram when tachycardia attacks.
      (3) Ventricular tachycardia is different from bundle branch reciprocal
      ventricular tachycardia.

PMID- 15257924
TI  - [Closed abdominal injuries: clinical analysis of 246 cases].
AB  - OBJECTIVE: To explore the approaches for early diagnosis and effective management
      of closed abdominal injures. METHODS: The experience in diagnosis and management
      of 246 cases of closed abdominal injuries was analyzed. RESULTS: Of the 246
      patients treated in the past 5 years, 221 underwent exploratory laparotomy and 25
      received conservative treatment. Altogether 235 patients (95.53%) were cured and
      11 died (4.47%). CONCLUSION: Systemic physical examination and early diagnoses
      are crucial for successful management of closed abdominal injuries. Surgeons
      should be aware of the importance of early-stage anti-shock treatment and timely
      surgical management, and the indications and procedures for exploratory
      laparotomy should be strictly followed.

PMID- 15257925
TI  - [Diagnosis of intramedullary spinal cord ependymomas and astrocytomas using
      magnetic resonance imaging: analysis of 15 cases].
AB  - OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) features of
      intramedullary spinal cord ependymomas(INSE) and astrocytomas. METHODS:
      Retrospective analyses of the MRI images were conducted in 15 cases of INSE and
      10 cases of astrocytoma. RESULTS: MRI appearances were similar in the 2 types of
      neoplasms, both showing enlargement of the involved spinal cord segments, low
      signal and blurred boundary on T1-weighted imaging, and high signal on T2
      weighted imaging. Peritumoral cyst formation were found in 16 patients. Contrast
      enhancement was homogeneous in 6 cases of ependymomas and 1 of astrocytoma,
      heterogeneous in 1 astrocytoma case, and no enhancement in 2 astrocytoma cases.
      CONCLUSION: MRI is helpful in the diagnosis and differential diagnosis of INSE
      and astrocytomas.

PMID- 15257926
TI  - The molecular basis of beta-thalassemia in Argentina. Influence of the pattern of
      immigration from the Mediterranean Basin.
AB  - In order to determine the molecular heterogeneity of the beta-thalassemia gene
      and to analyze the influence of immigration from the Mediterranean Basin, a total
      of 254 families (475 subjects) from Argentinean beta-thalassemia patients were
      investigated using molecular biology techniques. This allowed us to provide a
      simplified diagnosis and genetic counselling of this disorder in Argentina.

PMID- 15257927
TI  - The future of hemophilia treatment.

PMID- 15257928
TI  - Molecular basis and hematologic characterization of deltabeta-thalassemia and
      hereditary persistence of fetal hemoglobin in Thailand.
AB  - BACKGROUND AND OBJECTIVES: Hereditary persistence of fetal hemoglobin (HPFH) and
      deltabeta-thalassemia are heterogeneous disorders characterized by increased
      levels of Hb F in adult life. The distinction between these two conditions is not
      always possible from routine hematologic analyses. This study investigated the
      hematologic and molecular characteristics of high HbF determinants in Thailand,
      and describes a rapid DNA-based assay to facilitate diagnosis in a routine
      laboratory. DESIGN AND METHODS: A multiplex allele-specific polymerase chain
      reaction (PCR) system for rapid detection of three common DNA deletions causing
      (deltabeta)0-thalassemia and HPFH in South-east Asians was developed and used to
      examine the molecular basis for the high Hb F phenotypes in 273 unrelated Thai
      individuals. Hematologic data were recorded and correlated to the molecular
      findings. RESULTS: The multiplex PCR system was validated and results were
      completely concordant with those of other established methods. DNA analysis
      identified GgAg(deltabeta)0-thalassemia in 148 cases (54.2%), deletional HPFH-6
      in 83 (30.4 %) and the deletion-inversion Ggamma(Agammadeltabeta)0-thalassemia in
      22 (8.1 %) cases, while another 20 (7.3 %) subjects remained uncharacterized.
      Genotype-phenotype relationships are discussed. INTERPRETATION AND CONCLUSIONS:
      These data emphasize the high frequencies of deltabeta-thalassemia and HPFH in
      Thailand and the need for differential diagnostic methods since the hematologic
      parameters associated with the conditions are very similar and overlap. The
      multiplex allele-specific PCR approach should prove useful in complementing
      routine Hb analysis for the differential diagnosis of these three common causes
      of high Hb F determinants and should facilitate a program of hemoglobinopathy
      screening in the region.

PMID- 15257930
TI  - Feasibility and results of autologous stem cell transplantation in de novo acute
      myeloid leukemia in patients over 60 years old. Results of the CETLAM AML-99
      protocol.
AB  - BACKGROUND AND OBJECTIVES: The benefits of high-dose cytarabine, anthracyclines
      and hematopoietic stem cell transplantation in the treatment of acute myeloid
      leukemia (AML) are greater in younger rather than in older patients. We assessed
      the proportion of patients over 60 years with de novo AML who qualified for
      intensive therapy and determined the feasibility and results of autologous stem
      cell transplantation (ASCT) in first complete remission (CR). DESIGN AND METHODS:
      Induction therapy included idarubicin, cytarabine and etoposide. Patients who
      achieved CR received one cycle of mitoxantrone and cytarabine and ASCT as
      consolidation therapies. RESULTS: Over a 4-year period, 258 patients were
      registered of whom 135 (52%) were enrolled for intensive treatment. The CR rate
      was 61%, advanced age (p=0.033) and unfavorable cytogenetics (p=0.015) emerged as
      independent negative prognostic factors for CR. The 2-year overall survival (OS)
      was 23 % (CI 14%-30%) and was poorer in patients with unfavorable cytogenetics
      (p=0.035), age over 70 years (p=0.019) or leukocytosis (p=0.006). Only 27% of the
      potential candidates underwent ASCT. The probability of 2-year leukemia-free
      survival after consolidation was 39% (CI 6%-71%) for these patients and 22% (CI
      6% - 39%) for candidate patients not undergoing ASCT (p=0.07). INTERPRETATION AND
      CONCLUSIONS: Over 25% of the patients 60 to 70 years with de novo AML benefit
      from standard intensive treatment. In these patients, ASCT has a tolerable
      toxicity and may have a positive impact on leukemia-free survival.

PMID- 15257929
TI  - Clinical effects and P-glycoprotein inhibition in patients with acute myeloid
      leukemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine.
AB  - BACKGROUND AND OBJECTIVES: P-glycoprotein (P-gp) is a major cause of multidrug
      resistance (MDR) in acute myelogenous leukemia (AML) and is thought to contribute
      to the failure of chemotherapy. Zosuquidar trihydochloride (Z.3HCL) is a potent
      and selective inhibitor of P-gp which rapidly and effectively inhibits drug
      efflux. DESIGN AND METHODS: The aim of this study was to evaluate the clinical
      effects of Z.3HCL and determine its influence on P-gp activity. Sixteen AML
      patients were entered into a phase 1 dose ranging clinical trial of Z.3HCL, co
      administered intravenously with daunorubicin and cytosine arabinoside (ARA-C).
      Clinical outcomes, toxicity abd adverse events were assessed. P-gp function was
      analyzed by flow cytometry. In vitro cytotoxicity was studied using the MTT
      assay. RESULTS: Eleven patients achieved a complete remission and one a partial
      remission with a median survival of 559 (range 38-906) days. Non-hematologic
      grade 3 and 4 toxicities were seen in 4 patients. Z.3HCL infusion was associated
      with rapid inhibition of Rh123 efflux in CD56+ cells in 16/16 patients and in
      CD33+ cells from 6/10 patients. The median inhibition was 95% for CD56+ cells and
      85.25% for CD33+ cells was significantly elevated in 6/16 patients. The median
      IC50, using a MTT assay for daunorubicin, decreased significantly between Z.3HCL
      modulated and unmodulated cells (n=11,153 and 247 ng/mL respectively, p=0.01).
      INTERPRETATION AND CONCLUSIONS: The modulator Z.3HCL is a specific inhibitor of P
      gp efflux and can be given safely to patients with AML in combination with
      induction doses of conventional cytotoxic drugs.

PMID- 15257931
TI  - Gene expression profiles and risk stratification in childhood acute lymphoblastic
      leukemia.
AB  - BACKGROUND AND OBJECTIVES: Childhood acute lymphoblastic leukemia (ALL) is a
      heterogeneous disease. There are several distinct genetic subtypes, characterized
      by typical changes in gene expression pattern. In addition to cytogenetic
      markers, the in vivo response to treatment is an emerging prognostic marker for
      risk stratification. However, it has not yet been reported whether gene
      expression profiles can predict risk group stratification already at the time of
      diagnosis. DESIGN AND METHODS: We analyzed bone marrow samples of 31 ALL patients
      to identify changes in gene expression that are associated with the current risk
      assignment, irrespective of the genetic subtype. Gene expression profiles were
      established using oligonucleotide microarrays. RESULTS: Considering all low- and
      high-risk patients, no gene was capable of predicting the risk assignment already
      at time of diagnosis. However, screening for risk group associated genes using
      more homogeneous subsets of patients revealed 10(6) discriminatory probe sets.
      The prognostic significance of these probe sets was subsequently determined for
      the entire series of patients. Using the selected subgroups as the training set
      and the remaining samples as an independent test set, logistic regression using 3
      predictor variables could accurately predict current risk assignment for 10 out
      of 12 patients. INTERPRETATION AND CONCLUSIONS: Gene expression profiles
      established from a cytogenetically heterogeneous study group are not, as yet,
      sufficiently accurate to be used prognostically in a clinical setting. Additional
      risk-associated gene expression analyses need to be performed in more homogeneous
      sets of patients.

PMID- 15257932
TI  - Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non
      Hodgkin's lymphoma for patients <or=50 years old in first complete remission:
      results of the EORTC ALL-3 trial.
AB  - BACKGROUND AND OBJECTIVES: In the EORTC ALL-3 trial, the efficacy of allogeneic
      transplantation was compared with that of autologous marrow transplantation and
      maintenance chemotherapy in patients <or= 50 years who reached CR. DESIGN AND
      METHODS: Among 340 patients who entered the study, 279 were <or=50 years old. Out
      of these, 220 reached CR, 184 patients started consolidation and were HLA typed;
      68 had a donor and 116 had no sibling donor. The median follow-up was 9.5 years;
      93 patients relapsed, 26 died in CR, and overall 116 patients died. Allogeneic
      transplantation was performed in 47 (68%) patients with a donor while autologous
      transplantation or maintenance chemotherapy was given to 84 (72%) patients
      without a sibling donor. RESULTS: The 6-year disease-free survival rate was
      similar in the groups with and without donor [38.2% (SE=5.9%) vs. 36.8%
      (SE=4.6%), hazard ratio 1.01, 95% CI 0.67-1.53]. Comparing the donor group with
      the no donor group, the former had a lower relapse incidence (38.2% vs. 56.3%,
      p=0.001), but a higher cumulative incidence of death in CR (23.5% vs. 6.9%,
      p=0.0004). The 6-year survival rates were similar [41.2% (SE=6.0%) vs. 38.8%
      (SE=4.6%)]. INTERPRETATION AND CONCLUSIONS: This trial did not show that
      allogeneic transplantation, when a sibling donor is available, produces a better
      outcome than the policy of offering autotransplantation or chemotherapy in the
      absence of a donor.

PMID- 15257933
TI  - Combined polymerase chain reaction methods to detect c-myc/IgH rearrangement in
      childhood Burkitt's lymphoma for minimal residual disease analysis.
AB  - BACKGROUND AND OBJECTIVES: The translocation t(8;14)(q24;q32), involving the c
      myc gene (8q24) and the immunoglobulin heavy chain (IgH) locus (14q32),
      represents about 75% of all chromosomal translocations in Burkitt's lymphoma
      (BL). Due to the large variability of the breakpoint region, only the recently
      improved long-distance LD-polymerase chain reaction (PCR) allows the specific c
      myc/IgH fusion to be identified at the genomic level. The sensitivity of the LD
      PCR is only 10(-2) to 10(-3) due to the relatively large size of the
      amplification products (1 to 10 kbp). We, therefore, established a more sensitive
      nested PCR with a specific primer combination for each patient based on sequence
      analysis of the variant breakpoint regions. DESIGN AND METHODS: Using the
      combined PCR methods, we analyzed bone marrow and peripheral blood without
      visible blasts at diagnosis from 18 patients with t(8;14)-positive BL. RESULTS:
      In tests employing dilutions of genomic DNA from the BL cell line CA-46 in the T
      cell lymphoma cell line KARPAS-299, which lacks the t(8;14), the sensitivity
      increased 100-fold, to 10(-5). However, the investigation of 18 c-myc/IgH
      positive BL patients with each breakpoint-specific nested PCR showed an inter
      patient variability of sensitivity between 10(-3) and 10(-5). Using this assay,
      the rearrangement was detected in 4/16 bone marrow samples and in 6/15 peripheral
      blood samples without visible blasts at diagnosis. INTERPRETATION AND
      CONCLUSIONS: Using the combined PCR methods the detection of c-myc/IgH reaches a
      level of sensitivity required for the evaluation of minimal residual disease
      (MRD) in BL patients. Furthermore, the results highlight the importance of
      verifying the patient-specific sensitivity level for individual MRD monitoring.

PMID- 15257934
TI  - First-line therapy with thalidomide and dexamethasone in preparation for
      autologous stem cell transplantation for multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: The marked synergy of thalidomide and dexamethasone in
      advanced and refractory multiple myeloma (MM) provided the basis for a phase 2
      clinical study aimed at investigating the efficacy and toxicity of this
      combination as first-line therapy for patients less than 65 years old with newly
      diagnosed disease. DESIGN AND METHODS: Both thalidomide and dexamethasone were
      administered for 4 months in an attempt to reduce tumor cell mass before
      collection of peripheral blood stem cells (PBSC) and subsequent double autologous
      transplantation. Thalidomide was given at the fixed dose of 200 mg/day;
      dexamethasone was administered at the dose of 40 mg/day on days 1-4, 9-12 and 17-
      20 in odd cycles and 40 mg/day on days 1-4 in even cycles, repeated monthly.
      RESULTS: Seventy-one patients with symptomatic MM were evaluated for response and
      toxicity. On an intent-to-treat basis, the overall response (>or= partial
      remission) rate was 66%, including 17% of patients who attained a complete
      remission or a very good partial remission. In addition to common toxicity of
      thalidomide, deep-vein thrombosis was a troublesome adverse event (16%). Nine
      patients (13%) required thalidomide discontinuation because of toxicity,
      including 3 patients who died during the study treatment. Fifty-nine patients
      proceeded to PBSC mobilization and yielded a median number of 7.1x10(6) CD 34(+ )
      cells/kg. INTERPRETATION AND CONCLUSIONS: The combination of thalidomide and
      dexamethasone is an effective and relatively well tolerated induction regimen for
      previously untreated patients with MM. This combination may provide an oral
      alternative to vincristine-doxorubicin-dexamethasone in preparation for
      autologous stem cell transplantation.

PMID- 15257935
TI  - Extramedullary multiple myeloma escapes the effect of thalidomide.
AB  - BACKGROUND AND OBJECTIVES: Thalidomide is an antiangiogenic drug that produces a
      response rate ranging from 32 to 64% in patients with refractory/relapsed
      multiple myeloma (MM). However, the efficacy of thalidomide in patients with soft
      tissue plasmacytomas is controversial. The aim of this study was to assess the
      response rate to thalidomide in patients with advanced MM and to correlate the
      response rate with the presence of extramedullary involvement. DESIGN AND
      METHODS: Thirty-eight patients with refractory/relapsed MM were treated with
      thalidomide. Eleven patients had extramedullary involvement when therapy was
      initiated. The response rate was evaluated according to the criteria of the
      European Group for Blood and Marrow Transplantation. RESULTS: Sixteen of the 38
      patients (42%) responded to thalidomide. The response rate was significantly
      higher in patients without extramedullary involvement (59% vs 0%, p=0.0006).
      Although four of the 11 patients with extramedullary involvement had a
      serological response, a progression of the soft-tissue masses was observed in all
      of them. INTERPRETATION AND CONCLUSIONS: Thalidomide is effective in patients
      with advanced MM. However, extramedullary disease does not respond to
      thalidomide, as delivered in this series. The mechanisms to explain different
      response to therapy depending on tumor homing warrant further investigation.

PMID- 15257936
TI  - Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex
      vivo expansion of CD34(+) hematopoietic stem cells and for chondrogenic
      differentiation.
AB  - BACKGROUND AND OBJECTIVES: Human mesenchymal stem/progenitor cells (MSPC) ar
      pluripotent, being the precursors for marrow stroma, bone, cartilage, muscle and
      connective tissues. Although the presence of hematopoietic stem/progenitor cells
      (HSPC) in umbilical cord blood (UCB) is well known, that of MSPC has been not
      fully evaluated. DESIGN AND METHODS: In this study, we examined the
      immunophenotype, the supporting function in relation to ex vivo expansion of
      hematopoietic stem progenitor cells and the chondrogenic differentiation of
      cultured cells with characteristics of MSPC from UCB. When UCB nucleated cells
      were isolated and 107 cells cultured in IMDM with 20% fetal bovine serum, the
      mean number of adherent fibroblastlike colonies was 3.5+/-0.7/10(6) monuclear
      cells. RESULTS: UCB-derived MSPC could be expanded for at least 15 passages. In
      their undifferentiated state, UCB-derived MSPC were CD13(+), CD29(+), CD90(+),
      CD105(+), CD166(+), SH2(+), SH3(+), SH4(+), CD45(-), CD34(-), and CD14(-); they
      produced stem cell factor, interleukin 6 and tumor necrosis factor alpha. UCB
      derived MSPC cultured in chondrogenic media differentiated into chondrogenic
      cells. UCB-derived MSPC supported the proliferation and differentiation of
      CD34(+) cells from UCB in vitro. INTERPRETATION AND CONCLUSIONS: UCB-derived MSPC
      have the potential to support ex vivo expansion of HSPC and chondrogenic
      differentiation. UCB should not be regarded as medical waste. It can serve as an
      alternative source of mesenchymal stem cells and may provide a unique source of
      fetal cells for cellular and gene therapy.

PMID- 15257937
TI  - Kinetics and immunophenotypic characterization of circulating hematopoietic
      progenitor cells after peripheral blood stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: Hematopoietic progenitor cells (HPC) circulate in the
      peripheral blood (PB) before and after engraftment following autologous or
      allogeneic peripheral blood stem cell transplantation (PBSCT), although the
      characteristics of these cells are not known. CD34 protein is a reliable marker
      for identifying the fraction of hematopoietic cells in which HPC are contained.
      The CD34(+) cells represent a heterogeneous cell population consisting of both
      primitive uncommitted as well as pluripotent committed progenitors. The aim of
      this study was to investigate the kinetics and immunophenotypic characteristics
      of these post-transplant circulating progenitor cells. DESIGN AND METHODS: Forty
      seven auto-PBSCT and nine allo-PBSCT recipients were selected for this study.
      Samples of PB were taken from each patient 4, 9, 11, 14, 16 and 18 days after the
      transplant. Cells were incubated with the following combinations of monoclonal
      antibodies: CD34-FITC/CD90-PE/CD38-CyCrome; CD34-FITC/CD117-PE/HLA-DR-PerCP; CD34
      FITC/CD13-PE/CD33-CyCrome and the cells were then analyzed by flow cytometry.
      RESULTS: CD34(+) cells were undetectable on day +4; they reappeared from day +9
      to day +18 along with neutrophil and platelet recovery. Subsets of CD34(+) HPC
      enriched in pluripotent stem cells (CD90(+)/CD38(low) or HLADR-) were hardly
      detected during the very early post-transplant period. HPC that expressed myeloid
      associated antigens (CD33, CD13, and CD117) increased after engraftment and
      constituted the largest proportion of the hematopoietic progenitor cells.
      INTERPRETATION AND CONCLUSIONS: Circulating HPC could be detected in the early
      period after PBSCT. The qualitative and quantitative composition of these cells
      is similar to that found among HPC from mobilized PB.

PMID- 15257938
TI  - Cryptococcosis in patients with hematologic malignancies. A report from GIMEMA
      infection.
AB  - BACKGROUND AND OBJECTIVES: Cryptococcosis is an important cause of morbidity and
      death in immunocompromised patients. The aim of this study was to evaluate
      clinical and laboratory characteristics, and outcome of patients with
      cryptococcosis complicating hematologic diseases. DESIGN AND METHODS: This was a
      retrospective study, conducted over a ten-year period (1993-2002) in 21
      hematology divisions, in tertiary care or university hospitals. RESULTS: This
      study evaluated 17 patients with hematologic diseases who developed
      cryptococcosis. Possible risk factors recognized before the onset of the
      infection were: administration of steroids for the underlying malignancy (6
      patients), diabetes mellitus (4 patients), cutaneous lesions (2 patients) and
      autoimmune disease, hepatic cirrhosis, chronic renal failure and exposure to
      pigeons (1 patient each). Five patients received prophylaxis, consisting of
      fluconazole in 2 cases. Fever, neurological and respiratory signs developed
      according to the primary sites of infection (5 blood, 5 central nervous system, 4
      lung, and 1 each in gut, skin and mouth). Diagnosis was made by positive
      microbiological culture, antigen detection in serum or cerebrospinal fluid, or
      polymerase chain reaction. All patients started specific treatment (fluconazole,
      7 patients; amphotericin-B deoxycolate or liposomal amphotericin-B, 10 patients).
      Two patients died from cryptococcosis within 30 days after diagnosis.
      INTERPRETATION AND CONCLUSIONS: Cryptococcosis in patients with hematologic
      malignancies is a rare complication. In neutropenic patients, it is less fatal
      than other fungal infections (i.e. aspergillosis or candidemia). Specific
      treatment, started promptly, positively influences the outcome.

PMID- 15257939
TI  - Management of coumarin-associated coagulopathy in the non-bleeding patient: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVES: Excessive anticoagulation is a frequent complication
      of anticoagulant therapy. The risk of hemorrhage approximately doubles for each
      one point increase in the International Normalized Ratio (INR) above 3.0.
      Reducing a prolonged INR to within the desired therapeutic range requires that
      oral anticoagulants be withheld. In addition, vitamin K may be administered.
      Since this latter treatment can produce rapid reductions in the INR, it must be
      carefully tailored to meet individual needs, balancing the risk of bleeding
      against the potential risk of causing thromboembolism. METHODS: To review
      available literature on the management of coumarin-associated coagulopathy in
      asymptomatic patients, a Medline search was carried out and papers published in
      English from 1966 and 2003 were identified. All available information on the
      management of asymptomatic patients presenting with coumarin-associated
      coagulopathy was analyzed. RESULTS: Following the results of clinical studies
      that only used an elevated INR as a surrogate end-point for the risk of bleeding,
      low dose oral vitamin K appears as the preferable strategy for rapidly restoring
      therapeutic INR levels in asymptomatic patients who present with an excessively
      prolonged INR due to warfarin therapy. For the treatment of patients with
      asymptomatic acenocoumarol-induced coagulopathy, vitamin K does not add any
      benefit to the strategy of simply withholding oral anticoagulant treatment.
      INTERPRETATION AND CONCLUSIONS: Large randomized trials using clinical end-points
      are now required to provide evidence-based treatment recommendations for patients
      with coumarin-associated coagulopathy.

PMID- 15257940
TI  - Childhood sickle cell crises: clinical severity, inflammatory markers and the
      role of interleukin-8.
AB  - There is emerging consensus that a pro-inflammatory condition contributes to the
      vaso-occlusive complications of sickle cell disease (SCD). We evaluated the
      potential value of inflammatory mediators as early markers of severity of painful
      vaso-occlusive crises (VOC) in SCD. We assayed the plasma levels of cytokines,
      soluble vascular cell adhesion molecule-1, acute phase proteins, secretory
      phospholipase and standard hematologic indices.

PMID- 15257941
TI  - NRAS, FLT3 and TP53 mutations in patients with myelodysplastic syndrome and a
      del(5q).
AB  - Mutations of the NRAS and TP53 genes and internal tandem duplication (ITD) of the
      FLT3 gene are among the most frequently observed molecular abnormalities in the
      myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We sought to
      determine the incidence of these abnormalities in patients with MDS and a 5q
      deletion. NRAS and FLT3 mutations are uncommon in MDS patients with a 5q deletion
      and TP53 mutation is associated with the more advanced MDS subtypes.

PMID- 15257942
TI  - Prognostic factors in myelodysplastic and myeloproliferative types of chronic
      myelomonocytic leukemia: a retrospective analysis of 83 patients from a single
      institution.
AB  - We analyzed independent prognostic factors associated with survival and risk of
      evolution to acute leukemia in our series of 83 patients with previously
      untreated chronic myelomonocytic leukemia (CMML), with the aim of testing the
      validity of the stratification based on white blood cell (WBC) count, in
      myeloproliferative and myelodysplastic types of the revisited WHO classification.

PMID- 15257943
TI  - TP53 codon 72 polymorphism in patients with chronic myeloid leukemia.
AB  - A single nucleotide polymorphism at TP53 codon 72 means that two alleles exist:
      A1 (proline residue, Pro72) and A2 (arginine residue, Arg72). The Pro72 variant
      of p53 has a lower apoptotic potential. We found that allele A1 was more frequent
      in patients with chronic myeloid leukemia (CML) than in controls, and among CML
      patients who had no cytogenetic response than among responders.

PMID- 15257944
TI  - Polyethylene glycol interferon-alpha2b alone or in combination with low-dose Ara
      C in patients newly diagnosed with chronic myeloid leukemia.
AB  - Thirty-five patients newly diagnosed with chronic myeloid leukemia received
      pegylated interferon alpha-2b (PEG-IFN) alone or combined with intermittent Ara-C
      for a median of 6.5 months (range: 1.4-19.2). The median weekly PEG-IFN dose was
      4.0 microg/kg. Complete hematologic, major and complete cytogenetic responses
      were observed in 73%, 32% and 14%, respectively. Extra-hematologic side-effects
      were frequent and 20% of patients had grade III-IV hematologic toxicity.

PMID- 15257945
TI  - FIP1L1-PDGFRA and c-kit D816V mutation-based clonality studies in systemic mast
      cell disease associated with eosinophilia.
AB  - Laboratory methods to detect both FIP1L1-PDGFRA and c-kit D816V mutations were
      combined with immunomagnetic cell separation to study the extent of clonal
      involvement by both myeloid and lymphoid cells in 3 patients with systemic
      mastocytosis associated with eosinophilia. The results suggested an early stem
      cell origin for the FIP1L1-PDGFRA mutation.

PMID- 15257946
TI  - Detection of bcl-2 rearrangement in mucosa-associated lymphoid tissue lymphomas
      from patients with hepatitis C virus infection.
AB  - It has been shown that t(14;18)(q32;q21) involving fusion of IGH with MALT1
      occurs frequently in mucosa-associated lymphoid tissue (MALT) lymphomas. Results
      of the present study indicate that the classical form of t(14;18)(q32;q21)
      involving fusion of IGH with bcl-2 can be detectable in a subset of MALT
      lymphomas in patients with hepatitis C virus (HCV) infection.

PMID- 15257947
TI  - Rituximab monotherapy is effective in patients with poor risk refractory
      aggressive non-Hodgkin's lymphoma.
AB  - We report the results of rituximab monotherapy in 21 patients with refractory or
      relapsed aggressive non Hodgkin s lymphoma (NHL). The majority of the patients
      (16/21) were refractory to conventional treatment and not eligible for high dose
      chemotherapy. Responses (1 complete and 6 partial) were achieved in some of these
      patients and their median overall survival was 8 months.

PMID- 15257948
TI  - Malignant evolution of monoclonal gammopathy of undetermined significance:
      analysis of 633 consecutive cases with a long term follow-up.
AB  - In 633 consecutive patients with monoclonal gammopathy of undetermined
      significance (MGUS) the probability of malignant evolution was 9, 17 and 51 % at
      5, 10 and 15 years, respectively, after diagnosis. The values of monoclonal
      component, Bence-Jones proteinuria and erythrocyte sedimentation rate were
      associated with malignant transformation.

PMID- 15257949
TI  - Homozygosity of the T allele of the 46 C-->T polymorphism in the F12 gene is a
      risk factor for acute coronary artery disease in the Spanish population.
AB  - Following new guidelines that contain recommendations on the desirable features
      of a genetic association study, we performed a case-control study to establish
      the risk of acute coronary artery disease (CAD) related to the polymorphism (46 C
      ->T) in the F12 gene. We found a 6-fold higher risk of acute CAD associated with
      the homozygosity of the T allele of the F12, 46C-->T polymorphism in the Spanish
      population.

PMID- 15257950
TI  - Risk of acute coronary artery disease associated with functional thrombin
      activatable fibrinolysis inhibitor plasma level.
AB  - To our knowledge, there is little information about functional thrombin
      activatable fibrinolysis inhibitor (TAFI) levels and the risk of acute coronary
      artery disease (CAD). We investigated the risk of acute CAD related to plasma
      levels of functional TAFI. We found that functional TAFI levels in plasma (above
      126%), increased the risk of acute CAD almost 4-fold.

PMID- 15257951
TI  - High-dose granulocyte colony-stimulating factor mobilizes a higher proportion of
      early CD34(+) CD33(-) hemopoietic progenitors in children receiving treatment for
      solid tumors.
AB  - A relationship between dose of granulocyte colony-stimulating factor (G-CSF) and
      maturational stage of the progenitors mobilized in healthy adult donors has been
      suggested. In this study we characterize the progenitors mobilized by 2 different
      dosages of G-CSF in children receiving autologous grafts after intensive
      treatment for solid tumors.

PMID- 15257952
TI  - Polymorphism of the alpha4-subunit of VLA-4 integrin and bone marrow
      transplantation.
AB  - Integrin alpha4beta1 is an important homing molecule on stem cells. Two genetic
      variants of this integrin are known, alpha4-mas and alpha4-tex. We assessed the
      potential influence of this polymorphism in 37 patients undergoing allogeneic
      bone marrow transplantation. None of the constellations of variants influenced
      the outcome, as determined by the recovery of leukocytes or platelets,
      hospitalization time, and the development of graft-versus-host disease.

PMID- 15257953
TI  - Reduced intensity conditioning allogeneic transplant for advanced chronic
      lymphocytic leukemia.
AB  - We report the preliminary results of 12 patients with advanced stage chronic
      lymphocytic leukemia (CLL) transplanted following reduced intensity conditioning
      (RIC. With a median of 22 months of follow-up, 9 patients are alive and 3 have
      died of progressive disease, graft-versus-host disease (GVHD) or toxic hepatitis.
      Acute grade I-III GVHD occurred in 33% of patients and chronic GVHD in 50%. Eight
      of the 12 patients achieved a complete remission (CR) and 2 patients a partial
      remission (PR). Donor lymphocyte infusion was effective in 6 patients. Event-free
      survival, progression-free survival and non-relapse mortality at 3 years were
      68%, 42% and 16%, respectively. Our results show successful immunomodulation and
      reduction in tumor burden in high risk CLL.

PMID- 15257954
TI  - Graft-versus-leukemia effect of allogeneic stem cell transplantation; a Japanese
      single center study.
AB  - To clarify graft-versus-leukemia effect of graft-versus-host disease, we studied
      166 patients treated with allogeneic stem cell transplantation for hematologic
      malignancies. The cumulative incidence of relapse in patients with acute GVHD was
      significantly lower than that in patients without acute GVHD, but there was no
      similar GVL effect for chronic GVHD.

PMID- 15257955
TI  - Infectious disease markers in autologous blood donors and first-time volunteer
      blood donors: 14 years' experience in a blood center.
AB  - The proportion of blood donors with positive infectious disease markers was
      statistically higher in our population of 3,614 autologous donors than in our
      population of 276,106 first-time volunteer donors (p<0.005). Our data suggest
      that our autologous donor population is not as safe as our first-time volunteer
      donor population.

PMID- 15257956
TI  - Strengths and weaknesses of established indirect models to detect recombinant
      human erythropoietin abuse on blood samples collected 48-hr post administration.
AB  - We studied indirect detection models of erythropoietin abuse (EPO) on blood
      samples collected 48-hr after administration of the drug during 6 weeks of
      recombinant human erythropoietin (rHuEPO) treatment. Although the efficiency of
      OFF-models was preserved, we found a loss of sensitivity of ON-models. This study
      also revealed an increased percentage of stomatocytes in athletes receiving
      rHuEPO

PMID- 15257957
TI  - Response of prostate cancer during imatinib therapy in a patient with chronic
      myeloid leukemia.

PMID- 15257958
TI  - Concurrent hyperreactive malarial splenomegaly and quartan malarial nephropathy -
      Plasmodium malariae revisited.

PMID- 15257959
TI  - Failure of a sibling umbilical cord blood transplantation to correct hemophilia
      A.

PMID- 15257960
TI  - Clonal stability of initial leukemia in a child with central nervous system
      relapse 7.4 years after bone marrow relapse of common acute lymphoblastic
      leukemic.
AB  - Second central nervous system (CNS) relapses represent about 7.3% of subsequent
      recurrences of childhood acute lymphoblastic leukemia (ALL). In most children
      these subsequent CNS relapses occur during the first 18 months after diagnosis of
      the first relapse (mean 1.42 +/- 0.73 years). We present a patient who suffered a
      second ALL relapse in the CNS more than seven years after diagnosis of his first
      relapse. The leukemic clone was completely stable over more than ten years as
      shown by minimal residual disease techniques. Possible reasons for the recurrence
      of the leukemic clone after this very long period of dormancy (e.g. role of the
      disease site, immune system dysfunction) are discussed.

PMID- 15257961
TI  - Traumatic left shoulder fracture masking aggressive granuloblastic sarcoma in a
      CML patient.

PMID- 15257962
TI  - Chemotherapy-induced leukonychia.

PMID- 15257963
TI  - Survival in elderly acute myeloid leukemia patients.

PMID- 15257966
TI  - Facilitating participation of students with severe disabilities: aligning school
      based occupational therapy practice with best practices in severe disabilities.
AB  - School-based occupational therapy is the largest employer of occupational
      therapists. School-based occupational therapists work extensively with students
      with severe disabilities. Over the past decade, one significant change in the
      field of severe disabilities has been the advocacy of best practices. This paper
      discusses the implications of best practices for school-based occupational
      therapy practice and examines strategies that occupational therapists use to
      tackle such challenges. Focuses of the discussions are centered on the issues
      relative to curriculum, educational setting and instructional strategies. The
      theme of Activity and Participation proposed in International Classification of
      Functioning (WHO, 2001) guides our discussions. Specific strategies in aligning
      school-based occupational therapy practice with best practices in severe
      disabilities are proposed and highlighted.

PMID- 15257967
TI  - Validity and reliability of the school function assessment in elementary school
      students with disabilities.
AB  - This study examined validity of the School Function Assessment (SFA) and
      interrater reliability of occupational therapist and teacher ratings of students'
      school function. The validity of the SFA was examined using the known-group
      method in 35 participants in kindergarten through 7th grade attending elementary
      schools; 15 students with learning disabilities (LD), 11 students with autism,
      and 9 students with traumatic brain injury (TBI). The SFA criterion scores for
      the 23 individual scales were clustered into five distinct parts for the validity
      analyses. Significant differences in SFA scores among the 3 groups of students
      were found using Kruskal-Wallis analyses (Chi2 ranged from 9.28 to 20.55, p
      <.01). Two discriminant analyses demonstrated high correct classification of
      students with autism and LD, but showed less accurate classification of students
      with TBI, indicating that the SFA scores of students with TBI did not fall into a
      systematic pattern for classification. For the interrater reliability study, 16
      students' ratings by their teacher and occupational therapist were analyzed.
      Intraclass correlations resulted in moderate relationships between teacher and
      occupational therapist ratings for the average criterion scores for the three
      main sections of the SFA: participation,.70; task supports,.68; and activity
      performance,.73. Results of this study are discussed in terms of validity of
      score interpretation and the reliability of different team members completing the
      SFA questionnaire.

PMID- 15257968
TI  - Use of weighted vests in pediatric occupational therapy practice.
AB  - The aim of this study was to investigate pediatric occupational therapists'
      general experience and practice with weighted vests and their impressions about
      whether weighted vests are effective in changing specific behaviors of children
      with whom they have used weighted vests. A survey was mailed to a random sample
      of 514 pediatric occupational therapists who belonged to the School-Based Systems
      Special Interest Section or the Sensory Integration Special Interest Section of
      the American Occupational Therapy Association. The response rate was 68%. The
      survey included 43 items which covered therapist opinions, procedures, behavioral
      observations and knowledge about weighted vests, in addition to demographic
      information. Respondents who use weighted vests were more likely to have advanced
      degrees or certifications and more years of experience as pediatric therapists.
      They reported using weighted vests with preschool and young elementary school
      aged children with the diagnoses of autism or attention deficit disorder. Staying
      on task, staying in seat and attention span were the most common behaviors that
      therapists reported improving when weighted vests were used.

PMID- 15257969
TI  - Reliability of the Pediatric Evaluation of Disability Inventory (PEDI).
AB  - Pediatric Evaluation of Disability Inventory (PEDI) is an instrument for
      evaluating function in children with disabilities aged 6 months to 7.5 years. The
      PEDI measures both functional performance and capability in three domains: (1)
      self-care, (2) mobility, and (3) social function. The PEDI has recently been
      translated into Norwegian. The purpose of this study was to investigate the inter
      rater, inter-respondent and intra-rater reliability of the Norwegian version of
      the PEDI. Reliability was investigated in a sample of 30 Norwegian children
      without disabilities between 1.0 and 5.0 years. Interviews with parents were
      conducted twice by the same occupational therapist, and once by a
      physiotherapist. Kindergarten teachers were also interviewed by the occupational
      therapist. Using children without disabilities allows us to set up a standard for
      functional ability. Deviation from the point may indicate improvement or
      worsening of the state. The inter-rater and intra-rater part of the study showed
      excellent agreement of the observations, indicated both by small differences and
      high Intraclass Correlation Coefficients (ICC) (0.95-0.99). The discrepancy
      between the different interviews was highest between the reports from the parents
      and the kindergarten teachers (inter-respondent reliability), indicated by ICC
      from 0.64-0.74. Results of this study indicate that improved reliability is
      secured when the same interviewer interviews the same respondent, as well as when
      two trained interviewers interview the same respondent. The consistency of scores
      should be reviewed when different respondents are interviewed. Professionals
      administering the PEDI needs to be trained following a required procedure in
      order to secure consistency in their rating.

PMID- 15257971
TI  - Does opiophobia exist among pain specialists?

PMID- 15257972
TI  - Clinician beliefs about opioid use and barriers in chronic nonmalignant pain.
AB  - A survey of the medical directors of multidisciplinary pain clinics and
      multidisciplinary pain centers listed in the American Pain Society Pain
      Facilities Directory was conducted to define those pain specialists' beliefs
      about the role of opioid analgesia in 14 types of chronic nonmalignant pain.
      Respondents also reported their perceptions of barriers to their prescribing
      opioids for chronic nonmalignant pain and what they perceived as barriers to
      opioid prescribing for chronic nonmalignant pain by other, non-pain specialist
      clinicians in their communities. The respondents are characterized by
      demographics, disciplines, specialties, and time in practice. The percentage of
      time that a pharmacist was available in the pain programs also is reported. There
      is increasing acceptance of opioids for most of the listed types of chronic
      nonmalignant pain, but the acceptance varies by types of pain syndromes. Opioids
      were most consistently accepted for sickle cell disease pain and least commonly
      endorsed for headaches, myofascial pain, and fibromyalgia. Factors that may
      influence clinicians' perceptions about opioids are discussed.

PMID- 15257973
TI  - Prescribing and self-administration of morphine in Hispanic and non Hispanic
      Caucasian patients treated with patient-controlled analgesia.
AB  - The purpose of this study was to determine whether differences in either
      prescribing or self-administration of morphine exist between Hispanic and White
      (Caucasian) post-operative patients treated with patient-controlled analgesia
      (PCA). A review of the medical records of 30 Hispanic and 30 White patients who
      received postoperative PCA was conducted. Both prescribed and self-administered
      morphine were analyzed using a two-sided, two-sample Student's t-test. No
      differences in the amount of morphine prescribed (11.23 +/- 3.22 mg/hr in
      Hispanic patients, 11.05 +/- 4.28 mg/hr in White patients; p = 0.8503) or self
      administered (2.58 +/- 2.02 mg/hr in Hispanic patients, 3.32 +/- 3.00 mg/hr in
      White patients; p = 0.2711) were discovered. This study identified no
      statistically significant difference in either opioid prescribing or self
      administration between Hispanic and White post-operative patients.

PMID- 15257974
TI  - Modafinil for the treatment of pain-associated fatigue: review and case report.
AB  - Fatigue is a symptom that is frequently found in chronic pain patients with low
      back pain and/or neck pain. At the present time, no specific
      psychopharmacological treatment for this problem has been identified. Modafinil
      is a wakefulness-promoting agent that the FDA has approved for the treatment of
      excessive daytime sleepiness associated with narcolepsy. There have been reports
      on the use of modafinil for the treatment of fatigue in various neurological
      syndromes. This literature is reviewed. As such, modafinil treatment was
      initiated for a patient with severe fatigue associated with chronic low back pain
      and neck pain. There was dramatic improvement in fatigue and associated function.
      This case is described. It is the first such case report in the literature. The
      significance of this finding to the treatment of pain-associated fatigue is
      discussed.

PMID- 15257975
TI  - The treatment outcomes of pain survey (TOPS): a clinical monitoring and outcomes
      instrument for chronic pain practice and research.
AB  - The field of health outcomes research has increased the utilization of health
      related quality-of-life (HRQoL) instruments to document economic, clinical, and
      humanistic outcomes (ECHO). The Medical Outcomes Study Short Form 36-item
      Questionnaire (MOSSF-36, SF-36) has been utilized extensively in many disease
      states for this purpose, although it is not validated for use in chronic pain
      patients. The Total Outcomes of Pain Survey (TOPS) incorporates all the domains
      of the SF-36, and includes additional domains relevant in the management of
      chronic pain patients. The TOPS is well validated in these patients. In addition
      to its utility as an outcomes research tool, the TOPS is sensitive enough to
      document clinical changes in individual patients, making it a useful assessment
      tool for clinicians.

PMID- 15257976
TI  - Report from the ASHP Midyear Clinical Meeting.
AB  - The American Society of Health-System Pharmacists 2003 annual Midyear Clinical
      meeting in December 2003 was attended by nearly 18,000 individuals and had
      increased content and networking opportunities of Pharmacists involved in pain
      management. Initiatives, awards and services presented and announced at the
      meeting are described.

PMID- 15257977
TI  - Bibliographic databases on the World Wide Web: Nathan Cherny's palliative care
      resource.
AB  - The usefulness and limitations of bibliographic database software is discussed.
      As an excellent example of how this medium can be used, the electronic database
      on palliative care developed by Dr. Nathan Cherny that is available on the World
      Wide Web is described.

PMID- 15257978
TI  - Back pain and productivity: measuring worker productivity from an employer's
      perspective.
AB  - Most non-elderly Americans receive their health insurance coverage through their
      workplace. Employers, who historically saw the provision of this benefit as only
      an incentive for recruitment and retention, are now beginning to appreciate the
      value of health coverage and its effect on organizational performance and
      productivity. Back pain is a major contributor to reduced worker productivity and
      management of back pain is a major driver for prescribing of analgesic
      pharmacotherapy. This article examines various methods to assess productivity
      gains or losses, from an employer's perspective.

PMID- 15257979
TI  - Evidence-based pain management and palliative care in issues three and four for
      2003 of The Cochrane Library.
AB  - The Cochrane Library of systematic reviews is published quarterly. Issue 3 for
      2003 of the library was published in May 2003. That issue contains 3058 reviews
      of which 1754 are in full text. The issue contains 85 new reviews and four of
      those are directly relevant to pain management and palliative care. Annotated
      bibliographies for those seven reviews are provided. Issue 4 for 2003 of The
      Cochrane reviews and 1344 protocols. The Cochrane trials database now stands at
      over at over 378,000 records with an additional 4626 summaries of non-Cochrane
      systematic reviews published in the general medical literature [(Database of
      abstracts of reviews of effectiveness (DARE)].

PMID- 15257980
TI  - Statement on intractable pain treatment acts.

PMID- 15257983
TI  - Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by
      alveolar cells in vivo and in vitro.
AB  - The effects of surfactant protein B (SP-B) and SP-C on the uptake of surfactant
      like liposomes by alveolar type II cells and alveolar macrophages were studied
      both in vivo and in vitro. In vivo, mechanically ventilated rats were
      intratracheally instilled with fluorescently labeled liposomes that had SP-B
      and/or SP-C incorporated in different concentrations. Consequently, the alveolar
      cells were isolated, and cell-associated fluorescence was determined using flow
      cytometry. The results show that the incorporation of SP-B does not influence the
      uptake, and it also does not in the presence of essential cofactors. The
      inclusion of SP-C in the liposomes enhanced the alveolar type II cells at a SP-C
      to lipid ratio of 2:100. If divalent cations (calcium and magnesium) were present
      at physiological concentrations in the liposome suspension, uptake of liposomes
      by alveolar macrophages was also enhanced. In vitro, the incorporation of SP-B
      affected uptake only at a protein-to-lipid ratio of 8:100, whereas the inclusion
      of SP-C in the liposomes leads to an increased uptake at a protein-to-lipid ratio
      of 1:100. From these results, it can be concluded that SP-B is unlikely to affect
      uptake of surfactant, whereas SP-C in combination with divalent cations and other
      solutes are capable of increasing the uptake.

PMID- 15257984
TI  - Antiproliferative effects of calcitonin gene-related peptide in aortic and
      pulmonary artery smooth muscle cells.
AB  - Pulmonary hypertension is characterized by vascular remodeling involving smooth
      muscle cell proliferation and migration. Calcitonin gene-related peptide (CGRP)
      and nitric oxide (NO) are potent vasodilators, and the inhibition of aortic
      smooth muscle cell (ASMC) proliferation by NO has been documented, but less is
      known about the effects of CGRP. The mechanism by which overexpression of CGRP
      inhibits proliferation in pulmonary artery smooth muscle cells (PASMC) and ASMC
      following in vitro transfection by the gene coding for prepro-CGRP was
      investigated. Increased expression of p53 is known to stimulate p21, which
      inhibits G(1) cyclin/cdk complexes, thereby inhibiting cell proliferation. We
      hypothesize that p53 and p21 are involved in the growth inhibitory effect of
      CGRP. In this study, CGRP was shown to inhibit ASMC and PASMC proliferation. In
      PASMC transfected with CGRP and exposed to a PKA inhibitor (PKAi), cell
      proliferation was restored. p53 and p21 expression increased in CGRP-treated
      cells but decreased in cells treated with CGRP and PKAi. PASMC treated with CGRP
      and a PKG inhibitor (PKGi) recovered from inhibition of proliferation induced by
      CGRP. ASMC treated with CGRP and then PKAi or PKGi recovered only when exposed to
      the PKAi and not PKGi. Although CGRP is thought to act through a cAMP-dependent
      pathway, cGMP involvement in the response to CGRP has been reported. It is
      concluded that p53 plays a role in CGRP-induced inhibition of cell proliferation
      and cAMP/PKA appears to mediate this effect in ASMC and PASMC, whereas cGMP
      appears to be involved in PASMC proliferation.

PMID- 15257985
TI  - Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and
      histamine by the isoprostane 8-iso-PGE2.
AB  - Isoprostanes are generated during periods of oxidative stress, which characterize
      diseases such as asthma and cystic fibrosis. They also elicit functional
      responses and may therefore contribute to the pathology of these diseases. We set
      out to examine the effects of isoprostanes on airway responsiveness to
      cholinergic stimulation. Muscle bath techniques were employed using isolated
      bovine tracheal smooth muscle. 8-Isoprostaglandin E2 (8-iso-PGE2) increased tone
      directly on its own, although the magnitude of this response, even at the highest
      concentration tested, was only a fraction of that evoked by KCl or carbachol.
      More importantly, though, pretreatment of the tissues with 8-iso-PGE2 (10 microM)
      markedly augmented responses to submaximal and even subthreshold concentrations
      of KCl, carbachol, or histamine, whereas maximal responses to these agents were
      unaffected by the isoprostane. The augmentative effect on cholinergic
      responsiveness was mimicked by PGE2 (0.1 microM) and by the FP agonists PGF2 (0.1
      microM) and fluprostenol (0.1 microM), but not by the EP3 agonist sulprostone
      (0.1 microM) or the TP agonist U-46619 (0.1 microM). Antagonists of EP1 receptors
      (AH-6809 and SC-19920, 10 microM) and TP receptors (ICI-192605, 1 microM) had no
      effect on 8-iso-PGE2-induced augmentation of cholinergic responsiveness. We
      conclude that 8-iso-PGE2 induces nonspecific airway smooth muscle
      hyperresponsiveness through a non-TP non-EP prostanoid receptor.

PMID- 15257986
TI  - Interferon-gamma: a key contributor to hyperoxia-induced lung injury in mice.
AB  - Hyperoxia-induced lung injury complicates the care of many critically ill
      patients who receive supplemental oxygen therapy. Hyperoxic injury to lung
      tissues is mediated by reactive oxygen species, inflammatory cell activation, and
      release of cytotoxic cytokines. IFN-gamma is known to be induced in lungs exposed
      to high concentrations of oxygen; however, its contribution to hyperoxia-induced
      lung injury remains unclear. To determine whether IFN-gamma contributes to
      hyperoxia-induced lung injury, we first used anti-mouse IFN-gamma antibody to
      blockade IFN-gamma activity. Administration of anti-mouse IFN-gamma antibody
      inhibited hyperoxia-induced increases in pulmonary alveolar permeability and
      neutrophil migration into lung air spaces. To confirm that IFN-gamma contributes
      to hyperoxic lung injury, we then simultaneously exposed IFN-gamma-deficient (IFN
      gamma-/-) mice and wild-type mice to hyperoxia. In the early phase of hyperoxia,
      permeability changes and neutrophil migration were significantly reduced in IFN
      gamma-/- mice compared with wild-type mice, although the differences in
      permeability changes and neutrophil migration between IFN-gamma-/- mice and wild
      type mice were not significant in the late phase of hyperoxia. The concentrations
      of IL-12 and IL-18, two cytokines that play a role in IFN-gamma induction,
      significantly increased in bronchoalveolar lavage fluid after exposure to
      hyperoxia in both IFN-gamma-/- mice and wild-type mice, suggesting that hyperoxia
      initiates upstream events that result in IFN-gamma production. Although there was
      no significant difference in overall survival, IFN-gamma-/- mice had a better
      early survival rate than did the wild-type mice. Therefore, these data strongly
      suggest that IFN-gamma is a key molecular contributor to hyperoxia-induced lung
      injury.

PMID- 15257987
TI  - Mechanisms of early pulmonary neutrophil sequestration in ventilator-induced lung
      injury in mice.
AB  - Polymorphonuclear leukocytes (PMN) play an important role in ventilator-induced
      lung injury (VILI), but the mechanisms of pulmonary PMN recruitment, particularly
      early intravascular PMN sequestration during VILI, have not been elucidated. We
      investigated the physiological and molecular mechanisms of pulmonary PMN
      sequestration in an in vivo mouse model of VILI. Anesthetized C57/BL6 mice were
      ventilated for 1 h with high tidal volume (injurious ventilation), low tidal
      volume and high positive end-expiratory pressure (protective ventilation), or
      normal tidal volume (control ventilation). Pulmonary PMN sequestration analyzed
      by flow cytometry of lung cell suspensions was substantially enhanced in
      injurious ventilation compared with protective and control ventilation, preceding
      development of physiological signs of lung injury. Anesthetized, spontaneously
      breathing mice with continuous positive airway pressure demonstrated that raised
      alveolar pressure alone does not induce PMN entrapment. In vitro leukocyte
      deformability assay indicated stiffening of circulating leukocytes in injurious
      ventilation compared with control ventilation. PMN sequestration in injurious
      ventilation was markedly inhibited by administration of anti-L-selectin antibody,
      but not by anti-CD18 antibody. These results suggest that mechanical ventilatory
      stress initiates pulmonary PMN sequestration early in the course of VILI, and
      this phenomenon is associated with stretch-induced inflammatory events leading to
      PMN stiffening and mediated by L-selectin-dependent but CD18-independent
      mechanisms.

PMID- 15257989
TI  - A proportional hazards model with time-dependent covariates and time-varying
      effects for analysis of fetal and infant death.
AB  - Birth-weight- and gestational-age-specific perinatal mortality curves intersect
      when compared by race and maternal smoking. The authors propose a new measure to
      replace fetal and infant mortality and an analytic strategy to assess the effects
      of risk factors on this outcome. They used 1998 data for US Blacks and Whites.
      Age-specific post-last menstrual period (LMP) mortality rate was defined as the
      proportion of deaths (stillbirth, perinatal death, or infant death) at a given
      age post-LMP. The authors used extended Cox regression with time-varying
      covariates and hazard ratios to model the effects of race and smoking on post-LMP
      mortality. Perinatal mortality rates (conventional calculation) for Blacks and
      Whites showed the expected crossover. However, analyses of post-LMP mortality
      showed no crossover. For the Black-White comparison, a hazard ratio of 1.72 (95%
      confidence interval: 1.67, 1.77) was obtained. The hazard was higher for smokers
      than for nonsmokers, but the hazard ratio increased from 1.09 (95% confidence
      interval: 0.98, 1.22) at 22 weeks to 1.82 (95% confidence interval: 1.72, 1.92)
      at 40 weeks. The hazard ratio associated with birth was also time dependent:
      higher than 1 for preterm gestation and lower than 1 for term gestation. The
      increasing adverse effect of smoking with gestational age suggests an
      accumulating effect of smoking on mortality. Modeling post-LMP mortality
      eliminates the crossover paradox for race and maternal smoking in a single
      statistical model.

PMID- 15257990
TI  - On the definition of gestational-age-specific mortality.
AB  - The "fetuses at risk" concept of gestational-age-specific mortality proposed by
      Yudkin et al. (Lancet 1987;1:1192-4) and extended by various researchers is
      becoming popular in perinatal and pediatric epidemiology. However, the
      definitions using this concept have led to a puzzling phenomenon in which
      mortality rates appear to increase monotonically with advancing gestational age.
      While proponents of this concept have highlighted the rationale for using as the
      denominator the number of fetuses at risk rather than that of fetuses delivered
      at a particular gestational week, many have not discussed how the numerator is
      derived. This article reviews various definitions of gestational-age-specific
      mortality rates. It points out that the definitions based on the concept of
      Yudkin et al. are indicators of short-term risk only. Furthermore, the seemingly
      monotonic positive association between mortality rates and gestational age is a
      misinterpretation. All of the definitions are valid when used and interpreted
      correctly. The choice of which definition to adopt depends on the specific issues
      one attempts to address. Calls for abandoning the conventional definitions are
      not justified.

PMID- 15257991
TI  - Invited commentary: what's so bad about curves crossing anyway?

PMID- 15257992
TI  - Invited commentary: analysis of gestational-age-specific mortality--on what
      biologic foundations?

PMID- 15257994
TI  - Breastfeeding and risk of atopic dermatitis, by parental history of allergy,
      during the first 18 months of life.
AB  - The role of breastfeeding in allergic diseases remains controversial. The authors
      studied the association between breastfeeding and development of atopic
      dermatitis during the first 18 months of life among children with and without a
      parental history of allergy. A cohort study of 15,430 mother-child pairs enrolled
      in The Danish National Birth Cohort was carried out between 1998 and 2000. Data
      on breastfeeding, atopic dermatitis, and potential confounders was obtained from
      telephone interviews conducted during pregnancy and when the children were 6 and
      18 months of age. The cumulative incidence of atopic dermatitis was 11.5% at 18
      months of age. Overall, current breastfeeding was not associated with atopic
      dermatitis (incidence rate ratio (IRR) = 0.91, 95% confidence interval (CI):
      0.80, 1.04). Exclusive breastfeeding for at least 4 months was associated with an
      increased risk of atopic dermatitis in children with no parents with allergies
      (IRR = 1.29, 95% CI: 1.06, 1.55) but not for children with one (IRR = 1.11, 95%
      CI: 0.94, 1.31) or two (IRR = 0.88, 95% CI: 0.69, 1.13) parents with allergies
      (test for homogeneity, p = 0.03). The authors found no overall effects of
      exclusive or partial breastfeeding on the risk of atopic dermatitis. However, the
      effect of exclusive breastfeeding for 4 months or more depended on parental
      history of allergic diseases.

PMID- 15257995
TI  - Effect of a nighttime magnetic field exposure on sleep patterns in young women.
AB  - Since poor sleep quality is associated with multiple health problems, it is
      important to understand factors that may affect sleep patterns. The purpose of
      this study was to determine the effect of a continuous, 60-Hz, nighttime magnetic
      field exposure on sleep outcomes in young women sleeping at home. The study was a
      randomized crossover trial, comparing intervention (0.5-1.0 micro T above ambient
      levels) with ambient magnetic field levels, during two 5-night measurement
      periods. Subjects lived in the Seattle, Washington, area and were 20-40 years of
      age, had regular menstrual cycles, were not taking oral contraceptives, and had
      not breastfed or been pregnant during the previous year. The study was conducted
      between March and September of 2001. Sleep outcomes were measured via actigraphy.
      The range of magnetic field exposure was 0.001-0.50 micro T during the ambient
      period and 0.41-1.21 micro T during the intervention period. Sleep outcomes were
      not significantly different between the intervention and the ambient measurement
      periods. The intervention magnetic field had no effect on sleep patterns,
      suggesting that this exposure may not be an important factor in predicting sleep
      of young women who sleep at home.

PMID- 15257996
TI  - Prevalence and patterns of gender-based violence and revictimization among women
      attending antenatal clinics in Soweto, South Africa.
AB  - Gender-based violence is a key health risk for women globally and in South
      Africa. The authors analyzed data from 1,395 interviews with women attending
      antenatal clinics in Soweto, South Africa, between November 2001 and April 2002
      to estimate the prevalence of physical/sexual partner violence (55.5%), adult
      sexual assault by nonpartners (7.9%), child sexual assault (8.0%), and forced
      first intercourse (7.3%). Age at first experience of each type of violence was
      modeled by the Kaplan-Meier method, and Cox hazard models with time-varying
      covariates were used to explore whether child sexual assault and forced first
      intercourse were associated with risk of violent revictimization in adulthood.
      Child sexual assault was associated with increased risk of physical and/or sexual
      partner violence (risk ratio = 2.43, 95% confidence interval: 1.93, 3.06) and
      with adult sexual assault by a nonpartner (risk ratio = 2.33, 95% confidence
      interval: 1.40, 3.89). Forced first intercourse was associated with increased
      risk of physical and/or sexual partner violence (risk ratio = 2.64, 95%
      confidence interval: 2.07, 3.38) and nonsignificantly with adult sexual assault
      by a nonpartner (risk ratio = 2.14, 95% confidence interval: 0.92, 4.98). This
      study confirms the need for increased attention by the public health community to
      primary and secondary prevention of gender-based violence, with a specific need
      to reduce risk among South African adolescents.

PMID- 15257997
TI  - Alcohol consumption and cognitive function in the Whitehall II Study.
AB  - The authors investigated the relation between alcohol consumption and cognitive
      function in a United Kingdom cohort study (4,272 men, 1,761 women) with median
      follow-up of 11 years. Measures of alcohol consumption were obtained at baseline
      (1985-1988) and four subsequent phases of data collection. Cognitive function
      (memory test, AH4, Mill-Hill, phonemic and semantic fluency) was assessed at
      phase 5 (1997-1999), when participants were aged 46-68 years. Of people who
      reported drinking alcohol in the past year, those who consumed at least one drink
      in the past week, compared with those who did not, were significantly less likely
      to have poor cognitive function. The beneficial effect extended to those drinking
      more than 240 g per week (approximately 30 drinks). The effect was stronger for
      women than men and was not confined to those with evidence of vascular disease.
      Similar associations were found in cross-sectional and longitudinal analyses. The
      relations were not explained by confounding by smoking and by physical and mental
      health and, to a large extent, were not mediated by cholesterol or blood
      pressure. However, the relations were weakened when social position was added to
      the model. The authors concluded that for middle-aged subjects, increasing levels
      of alcohol consumption were associated with better function regarding some
      aspects of cognition. Nonetheless, it is not proposed that these findings be used
      to encourage increased alcohol consumption.

PMID- 15257998
TI  - A prospective study of folate intake and the risk of pancreatic cancer in men and
      women.
AB  - Laboratory and human studies suggest that folate intake may influence the risk of
      some cancers. However, prospective information about the relation between folate
      intake and the risk of exocrine pancreatic cancer is limited. The authors
      examined the relation of dietary folate intake to the risk of pancreatic cancer
      in two large prospective US cohorts. Folate intake was assessed by food frequency
      questionnaire in 1984 in women and in 1986 in men. Multivariate relative risks
      were adjusted for age, energy intake, cigarette smoking, body mass index,
      diabetes, and height. During 14 years' follow-up in each cohort, 326 incident
      cases of pancreatic cancer were identified. Compared with participants in the
      lowest category of folate intake, participants in increasing 100- micro g
      categories of total energy-adjusted folate intake had pooled multivariate
      relative risks for pancreatic cancer of 1.08, 1.10, and 1.03 (95% confidence
      interval: 0.74, 1.43; p(trend) = 0.99). For energy-adjusted folate from food, the
      pooled relative risks for increasing 100- micro g categories of intake were 0.81,
      0.89, and 0.66 (95% confidence interval: 0.42, 1.03; p(trend) = 0.12). There was
      no statistical interaction between folate intake and methionine, alcohol, fat, or
      caffeine. The results from these two large prospective cohorts do not support a
      strong association between energy-adjusted folate intake and the risk of
      pancreatic cancer.

PMID- 15257999
TI  - Prediction of ischemic stroke risk in the Atherosclerosis Risk in Communities
      Study.
AB  - The authors assessed the increase in the predictivity of ischemic stroke (IS)
      resulting from the addition of nontraditional risk factors and markers of
      subclinical disease to a basic model containing only traditional risk factors
      (current smoking, diabetes mellitus, systolic blood pressure, antihypertensive
      therapy, prior coronary disease, and left ventricular hypertrophy) among 14,685
      middle-aged persons in the Atherosclerosis Risk in Communities Study.
      Participants were recruited from four US communities in 1987-1989. Risk
      prediction scores for IS through 2000 were estimated from Cox models. The ability
      to predict which persons would develop IS was assessed by means of the area under
      the receiver operating characteristic curve-the probability that persons with IS
      had a higher risk score than those without IS. Among 22 nontraditional factors
      considered, the joint addition of body mass index, waist:hip ratio, high density
      lipoprotein cholesterol, albumin, von Willebrand factor, alcohol consumption,
      peripheral arterial disease, and carotid artery wall thickness modestly and
      statistically significantly improved prediction of future IS over a risk score
      that included traditional factors. Further improvement was obtained by adding age
      and race. For women, the area under the receiver operating characteristic curve
      went from 0.79 to 0.83 to 0.84; for men, it went from 0.76 to 0.78 to 0.80. These
      modest improvements are not enough to influence clinical and public health
      efforts to reduce the community burden of IS.

PMID- 15258000
TI  - Epidemiology of invasive Streptococcus pneumoniae among Navajo children in the
      era before use of conjugate pneumococcal vaccines, 1989-1996.
AB  - Streptococcus pneumoniae is the most common cause of invasive bacterial disease
      among children worldwide. The authors aimed to determine the incidence, clinical
      characteristics, and serotype distribution of invasive pneumococcal disease (IPD)
      among Navajo children in the southwestern United States. Active population-based
      laboratory surveillance for IPD among resident members of the Navajo Nation under
      18 years of age was conducted between 1989 and 1996. During this 8-year period,
      706 cases of IPD were identified. The rate of disease varied by age, with the
      highest rate being observed among children aged 6-11 months (727 cases/100,000
      person-years), followed by children aged 0-11 months, 0-23 months, and 0-59
      months (568, 537, and 272 cases/100,000 person-years, respectively). Among
      children aged 0-23 months, 60.3% of cases were caused by serotypes in the seven
      valent conjugate pneumococcal vaccine (71.5% from 1989-1993 and 58.3% from 1994
      1996). Navajo children are at increased risk of IPD in comparison with the
      general US population. The distribution of disease-causing serotypes is similar
      to that of many countries in the developing world. Prevention strategies should
      include the use of licensed pneumococcal protein conjugate vaccine; however, a
      substantial proportion of disease is caused by nonvaccine serotypes. These data
      are critical for assessing the impact of these vaccines in this high-risk
      population.

PMID- 15258001
TI  - Construct validity of self-reported historical physical activity.
AB  - The purpose of this study was to determine the construct-related validity of self
      reported historical walking, running, and jogging (WRJ) activity on the basis of
      data from the Aerobics Center Longitudinal Study (Dallas, Texas). A total of
      4,100 men and 963 women underwent at least one medical examination between 1976
      and 1985 and completed a follow-up questionnaire in 1986. Levels of glucose,
      cholesterol, and triglycerides, resting systolic blood pressure, body mass index
      (weight (kg)/height (m)(2)), and cardiorespiratory fitness were measured at the
      time of the medical examination. The follow-up questionnaire assessed WRJ and
      other strenuous activities for each year from 1976 through 1985. Data analysis
      included Spearman and partial correlations, analysis of variance, analysis of
      covariance, and t tests. Results indicated significant correlations between
      recalled WRJ and treadmill times for each year throughout the 10-year period (r =
      0.40-0.61). Participants were classified as historically either sufficiently
      physically active to receive a health benefit or insufficiently active for a
      health benefit. Engaging in sufficient levels of historical WRJ was associated
      with higher treadmill times and lower body mass indices for men and women and
      lower triglyceride levels for men. Self-reported historical WRJ can be assessed
      with reasonable validity in comparison with measured treadmill performance, with
      no decay in accuracy of reporting for up to 10 years in the past.

PMID- 15258002
TI  - Estimating laboratory precision of urinary albumin excretion and other urinary
      measures in the International Study on Macronutrients and Blood Pressure.
AB  - Microalbuminuria is a risk factor for renal failure, stroke, and cardiovascular
      disease. However, estimating laboratory precision for albumin excretion is
      problematic because of its highly skewed distribution and the presence of values
      below assay detection limits. The authors used 781 quality control pairs from 24
      hour urine samples collected between 1996 and 1999 in the International Study on
      Macronutrients and Blood Pressure (INTERMAP) to compare percentage of technical
      error (%TE), the usual estimate of laboratory precision, with the mean and median
      values of within-pair coefficients of variation (CVs) for urinary albumin
      concentration and other urinary variables. In INTERMAP, %TE was larger than mean
      CV for all variables. Exclusion of potentially mislabeled samples reduced this
      difference; for example, for sodium, estimates of %TE and mean and median CV were
      2.37%, 0.75%, and 0.28%, respectively, for all 781 pairs and 0.84%, 0.48%, and
      0.27%, respectively, with possibly mislabeled pairs excluded. For urinary albumin
      concentration, exclusion of one mislabeled pair changed estimates for %TE and
      mean CV from 29.6% and 20.8% to 20.6% and 20.6%, while median CV was unchanged at
      9.4%. After exclusion of urinary albumin concentration pairs with values below
      the detection limit, estimates were 15.4%, 11.4%, and 6.4%, respectively. Results
      indicate that mean and median CV are not equivalent to %TE and that values below
      the detection limit can markedly affect estimates and should be excluded.

PMID- 15258003
TI  - Impact of a financial incentive on case and control participation in a telephone
      interview.
AB  - The authors investigated the effect of a 5.00 dollars incentive on participation
      in a telephone interview among cases and controls in an ongoing study of
      colorectal cancer. Cases and matched community controls were sent a letter
      introducing the study. One week later, a nurse called to invite the person to
      participate in a 30-minute telephone interview. After 1 year of data collection
      (which began in June 2001), the authors began enclosing a 5.00 dollars bill in
      the initial letter as an incentive. Incentives were mailed to all potential
      controls. The authors randomized 50% of a subset of cases to receive the
      incentive. In the year prior to institution of the incentive, 44.2% of 851
      controls participated in the interview, as compared with 56.2% of 1,043 controls
      in the year after the incentive was instituted (p < 0.001). Among cases
      randomized to receive the incentive (n = 199), 63.8% participated as compared
      with 68.4% in the nonincentive group (n = 193) (p > 0.05). Among cases aged 60-69
      years, the response rate in the incentive group was reduced by 17% (p = 0.03).
      Thus, among controls, a small monetary incentive appears to promote a feeling of
      goodwill toward the research. It does not seem to have an equivalent effect among
      cases, and in the worst case it may insult or annoy some cases who may otherwise
      have participated.

PMID- 15258004
TI  - Re: "wine, liquor, beer, and mortality".

PMID- 15258005
TI  - High hopes for cannabinoid analgesia.

PMID- 15258006
TI  - Does the cannabinoid dronabinol reduce central pain in multiple sclerosis?
      Randomised double blind placebo controlled crossover trial.
AB  - OBJECTIVE: To evaluate the effect of the oral synthetic delta-9
      tetrahydrocannabinol dronabinol on central neuropathic pain in patients with
      multiple sclerosis. DESIGN: Randomised double blind placebo controlled crossover
      trial. SETTING: Outpatient clinic, University Hospital of Aarhus, Denmark.
      PARTICIPANTS: 24 patients aged between 23 and 55 years with multiple sclerosis
      and central pain. INTERVENTION: Orally administered dronabinol at a maximum dose
      of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated
      by a three week washout period. MAIN OUTCOME MEASURE: Median spontaneous pain
      intensity (numerical rating scale) in the last week of treatment. RESULTS: Median
      spontaneous pain intensity was significantly lower during dronabinol treatment
      than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0
      to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was
      higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat
      for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36
      quality of life scale, the two items bodily pain and mental health indicated
      benefits from active treatment compared with placebo. The number of patients with
      adverse events was higher during active treatment, especially in the first week
      of treatment. The functional ability of the multiple sclerosis patients did not
      change. CONCLUSIONS: Dronabinol has a modest but clinically relevant analgesic
      effect on central pain in patients with multiple sclerosis. Adverse events,
      including dizziness, were more frequent with dronabinol than with placebo during
      the first week of treatment.

PMID- 15258007
TI  - Value based medicine.

PMID- 15258008
TI  - How do you know?

PMID- 15258009
TI  - Cost utility of photodynamic therapy for predominantly classic neovascular age
      related macular degeneration.
AB  - BACKGROUND/AIM: Age related macular degeneration (AMD) is the leading cause of
      severe vision impairment and blindness in older people throughout the developed
      world and currently affects around 420 000 UK citizens. Choroidal
      neovascularisation (CNV) is treatable with photodynamic therapy (PDT) but is
      expensive at over pound 1200 per treatment. The aim of this study was to assess
      the cost utility of PDT for better eye, predominantly classic, subfoveal
      choroidal neovascular lesions secondary to AMD. METHODS: Cost utility analysis
      (CUA) was conducted to estimate the cost effectiveness of PDT for scenarios
      involving reasonable (6/12) and poor (6/60) visual acuity. The models
      incorporated data from the Treatment of Age-related Macular Degeneration with PDT
      (TAP) Study and patient based utilities. The incremental CUA was based on
      decision analytical models, comparing treatment to a placebo comparator.
      Extensive one way sensitivity analysis of parameters was conducted to determine
      the robustness of the model. A discount rate of 6% was used for costs and quality
      adjusted life years (QALY). RESULTS: Model 1: in people with reasonable initial
      visual acuity, the cost utility of treating applicable neovascular AMD lesions
      was pound 31 607 per QALY saved, with a sensitivity analysis range from pound 25
      285 to pound 37 928. Model 2: in people with poor initial visual acuity, the cost
      utility was pound 63 214 per QALY saved, with a sensitivity analysis range from
      pound 54 183 to pound 75 856. CONCLUSIONS: PDT treatment is the only available
      treatment for some forms of neovascular ("wet") AMD. Under these assumptions, PDT
      can be considered moderately cost effective for those with reasonable visual
      acuity but less cost effective for those with initial poor visual acuity. These
      findings have implications for ophthalmic practice and healthcare planning.

PMID- 15258010
TI  - Risk factors for age related cataract in a rural population of southern India:
      the Aravind Comprehensive Eye Study.
AB  - AIM: To determine risk factors for lens opacities and age related cataract in an
      older rural population of southern India. METHODS: A cross sectional population
      based study of 5150 people aged 40 years and above from 50 clusters from three
      districts in southern India. The lens was graded and classified after dilation
      using LOCS III system at the slit lamp for cataract. Definite cataract was
      defined as nuclear opalescence >/=3.0 and/or cortical cataract >/=3.0 and/or PSC
      >/=2.0. RESULTS: Definite cataracts were found in 2449 (47.5%) of 5150 subjects
      and the prevalence of cataract increased with age. The age adjusted prevalence of
      cataract was significantly lower in males (p = 0.0002). Demographic risk factors
      increasing age and illiteracy-were common for the three subtypes of cataract;
      females were more likely to have cortical cataracts and nuclear cataracts.
      Additionally, nuclear cataracts were associated with moderate smoking (OR:1.28,
      95% CI:1.01 to 1.64), lean body mass indices (OR: 1.37, 95% CI: 1.17 to 1.59) and
      higher waist to hip ratios (OR: 0.67, 95% CI: 0.54 to 0.82); cortical cataracts
      with hypertension (OR: 1.39 95% CI:1.11 to 1.72), pseudoexfoliation (OR:1.53,95%
      CI:1.17 to 2.01), and moderate to heavy smoking; and posterior subcapsular
      cataracts with diabetes (OR:1.55, 95% CI:1.12 to 2.15), lean body mass (OR:1.32,
      95% CI:1.11 to 1.57), and high waist to hip ratios (OR: 0.77, 95% CI: 0.62 to
      0.94). CONCLUSIONS: Risk factors for age related cataract in this population do
      not appear to be different from those reported in other populations. Further
      studies are required to identify the reason for the high prevalence of age
      related cataract and to understand better the role of each risk factor for
      cataractogenesis in this population.

PMID- 15258011
TI  - A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft
      after excision of primary pterygium.
AB  - BACKGROUND: Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two
      known useful adjuvants in the prevention of pterygial recurrence. This study was
      conducted to compare the outcome of these two treatments. METHODS: Prospective
      study on consecutive cases of primary pterygium (February 2001 to March 2002)
      randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes
      or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular
      tissue invading the cornea >1.5mm) and complications for a period of one year.
      RESULTS: 115 eyes in 114 patients who completed the study were randomised to
      receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the
      MMC group and only one recurrence (1.9%) in the LCAU group. There was a
      statistically significant difference in the recurrence rate between the two
      groups (p = 0.04). There were a total of three conjunctival cysts, three
      symblephara, one granuloma, and one dellen. No other visually significant
      complications were encountered in either group. CONCLUSION: Although LCAU
      resulted in better one year success rates, it is technically more difficult and
      inapplicable in cases with previous limbal disturbance. Simple excision followed
      by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision.
      Choice of adjuvant should be carefully made based on assessment of recurrence
      risk, local practices, and surgeon's expertise.

PMID- 15258012
TI  - Penetrating keratoplasty: indications over a 10 year period.
AB  - AIMS: To determine the indications for penetrating keratoplasty (PK) at the
      Corneoplastic Unit and Eye Bank, UK, a tertiary referral centre, over a 10 year
      period. METHODS: Records of all patients who underwent PK at our institution
      between 1990 and 1999 were reviewed retrospectively. Of the 1096 procedures
      performed in this period, 784 records were available for evaluation (72%).
      RESULTS: Regrafting was the most common indication, accounting for 40.9% of all
      cases. Keratoconus was the second most common indication (15%), followed by
      Fuchs' endothelial dystrophy (9.3%), pseudophakic bullous keratopathy (7.6%), and
      viral keratitis (5.9%), which included both herpes simplex and herpes zoster and
      showed a statistically significant decreasing trend using regression analysis
      (p<0.005). Among the regraft subgroup, viral keratitis accounted for 21.2% as the
      underlying primary diagnosis. The most common cause for graft failure in the
      regraft subgroup was endothelial failure (41.8%). CONCLUSION: Regrafting is the
      leading indication for PK; viral disease-although declining-is the leading
      primary diagnosis.

PMID- 15258013
TI  - Exfoliation syndrome angle characteristics: a lack of correlation with amount of
      disc damage.
AB  - BACKGROUND/AIMS: The exact pathogenesis of glaucoma in exfoliation syndrome is
      unclear. There has been some suggestion that narrow angles are more common in
      exfoliation syndrome and that this may be a component in the disease. The degree
      of pigmentation has also been shown to influence the intraocular pressure. The
      aim was to determine whether gonioscopic features of the anterior chamber angle
      in patients with exfoliation syndrome correlate with severity of the glaucoma.
      METHODS: A prospective study of consecutive patients with exfoliation syndrome
      was carried out. 78 patients with exfoliation syndrome were examined by one
      clinician (GLS), and underwent gonioscopy and dilated funduscopy. RESULTS:
      Anterior chamber angle, level of iris insertion, degree of pigmentation and the
      presence or absence of a Sampaolesi line were not correlated with the degree of
      disc damage. CONCLUSIONS: There was no apparent association between angle
      characteristics and the severity of glaucoma in patients with exfoliation
      syndrome.

PMID- 15258014
TI  - Prospective study comparing lidocaine 2% jelly versus sub-Tenon's anaesthesia for
      trabeculectomy surgery.
AB  - AIMS: To compare the analgesic properties of lidocaine 2% jelly versus sub
      Tenon's anaesthesia with lidocaine 2% without adrenaline (epinephrine) for
      trabeculectomy surgery. METHODS: A prospective randomised clinical trial. 59
      consecutive patients scheduled for trabeculectomy at the Toronto Western Hospital
      were randomly assigned to topical unpreserved lidocaine 2% jelly or sub-Tenon's
      anaesthesia with 2% lidocaine. Both groups received a standardised sedative
      consisting of midazolam, fentanyl. and/or propofol. The visual analogue scale was
      utilised to measure intraoperative pain. Patient comfort, physician assessment of
      intraoperative patient compliance, volume of local anaesthetic used, need for
      supplemental anaesthesia, and any complications were recorded. The two groups
      were compared using the Student's t test. RESULTS: The sub-Tenon's anaesthesia
      group and the lidocaine 2% jelly group did not vary significantly in subjective
      pain score (18.3 (SD 16.2) v 19.8 (12.4) respectively, p = 0.739) and surgeons'
      satisfaction scale (3.6 (0.7) and 3.8 (0.6) respectively, p = 0.328). Four
      patients required additional anaesthesia, all of them in the sub-Tenon's group.
      CONCLUSION: Topical lidocaine 2% jelly is as effective as sub-Tenon's anaesthesia
      for pain control in patients undergoing trabeculectomy. Lidocaine 2% jelly is
      similar to sub-Tenon's anaesthesia in patient comfort and surgeon satisfaction.

PMID- 15258015
TI  - Does the site of filtration influence the medium to long term intraocular
      pressure control following microtrabeculectomy in low risk eyes?
AB  - AIMS: To evaluate the influence of varying surgical site on the medium to long
      term intraocular pressure (IOP) control in patients undergoing unenhanced small
      flap trabeculectomy (microtrabeculectomy) in eyes at low risk of failure.
      METHODS: A retrospective non-concurrent analysis was performed on two cohorts of
      patients who underwent unenhanced microtrabeculectomy at different sites by a
      single surgeon (SAV). The first cohort of eyes was part of a trial to study the
      astigmatic effect of microtrabeculectomy (results published elsewhere) and all
      had flaps centred at the 12 o'clock meridian (superior flaps). The second cohort
      consisted of eyes with flaps created on either side of the 12 o'clock-that is,
      superonasal in left eyes and superotemporal in right eyes. All case notes were
      reviewed for the preoperative and presenting IOPs, the number and duration of
      antiglaucoma medication use preoperatively and, postoperatively, any
      intraoperative, early, or late postoperative complications. All IOPs measured at
      6 months and then yearly intervals were recorded. The baseline characteristics
      and IOPs at each follow up were compared between the eyes with the superonasal
      and superotemporal flaps of the non-12 o'clock group against those with superior
      flaps in the 12 o'clock group up to a maximum of 72 months. Survival was assessed
      by the site of microtrabeculectomy, with failure considered as any IOP above 22
      and 15 mm Hg with or without medications. RESULTS: All patients had a minimum
      follow up of 12 months and 12/17 patients in the 12 o'clock group and 17/28 in
      the non-12 o'clock group completed the full follow up of 72 months. The IOPs at
      all points in time were lower in the left eyes with superonasal flaps compared to
      both the superior and the superotemporal groups. This difference was
      statistically significant between the three groups to the end of 4 years (p =
      0.001) and remains clinically significant thereafter with the mean last recorded
      IOPs of 15.9, 12.4 (p = 0.03), and 14.3 mm Hg in the superior, superonasal and
      superotemporal groups respectively, with a smaller mean number of drops in the
      non-12 o'clock group. Kaplan-Meier curves showed a significantly better outcome
      for the cutoff IOP of 15 mm Hg in the superonasal group (p = 0.003) compared with
      both the other groups. CONCLUSION: Eyes with superonasal flaps achieve and
      maintain lower IOPs when compared with both the superior and superotemporal
      flaps. The results suggest that, when a low target IOP is desired, the site of
      surgery in an unenhanced filtering procedure should be superonasally sited.

PMID- 15258016
TI  - A randomised, prospective study comparing trabeculectomy with viscocanalostomy
      with adjunctive antimetabolite usage for the management of open angle glaucoma
      uncontrolled by medical therapy.
AB  - AIMS: To compare trabeculectomy with viscocanalostomy augmented with adjunctive
      antimetabolite use for the control of intraocular pressure (IOP) in open angle
      glaucoma (OAG). METHODS: 45 patients (50 eyes) with uncontrolled OAG were
      randomised to either trabeculectomy (25 eyes) or a viscocanalostomy technique (25
      eyes). Preoperatively, all eyes were graded in terms of risk factors for drainage
      failure and were given intraoperative antimetabolites (5-fluorouracil 25 mg/ml (5
      FU), mitomycin C (MMC) 0.2 mg/ml and 0.4 mg/ml) according to a standard protocol.
      RESULTS: There were no significant differences between the groups in age, sex,
      type of OAG, preoperative medications, risk factors for drainage failure, and
      preoperative IOP. Mean follow up was 20 months (range 3-24 months). It was 12
      months or longer in all eyes, except two lost to follow up at 3 months. At 12
      months, complete success (IOP<21 mm Hg without antiglaucoma medications) was seen
      in 91% of eyes undergoing trabeculectomy, but in only 60% of eyes undergoing
      viscocanalostomy (p<0.02). Similarly, at the last follow up visit (mean 20
      months) complete success was seen in 68% of eyes undergoing trabeculectomy and
      34% with viscocanalostomy (p<0.05). In terms of qualified success (IOP<21 mm Hg
      with or without glaucoma medications) and mean IOP measurements postoperatively
      there were no difference between the groups, although the mean number of
      antiglaucomatous medications required postoperatively was less with
      trabeculectomy (0.39) than viscocanalostomy (1.04) (p<0.05). Needling procedures
      were more commonly required after trabeculectomy (p<0.02). YAG goniotomy was
      required in three eyes (13%) after viscocanalostomy. Early transient
      complications such as anterior chamber shallowing and encysted blebs were more
      common in the trabeculectomy group (p<0.05). Late postoperative cataract
      formation was similar between the two groups. CONCLUSION: In terms of complete
      success and number of antiglaucomatous medications required postoperatively, IOP
      control appears to be better with trabeculectomy. Viscocanalostomy is associated
      with fewer early transient postoperative complications.

PMID- 15258017
TI  - Congenital stationary night blindness and a "Schubert-Bornschein" type
      electrophysiology in a family with dominant inheritance.
AB  - BACKGROUND/AIMS: To present the clinical, psychophysical, and
      electrophysiological characteristics of a family with dominantly inherited
      congenital stationary night blindness (CSNB). METHODS: Five affected family
      members from three generations were ascertained. Four affected individuals
      underwent ophthalmic examination and electrodiagnostic investigations. Three
      affected individuals also underwent scanning laser ophthalmoscopy and
      psychophysical testing. RESULTS: Affected individuals reported night blindness
      from an early age. Visual acuities were normal. Fundal appearances were normal
      apart from one older patient showing areas of peripheral chorioretinal atrophy.
      Autofluorescence images showed no gross abnormality. International Society for
      Clinical Electrophysiology of Vision (ISCEV) standard electroretinography (ERG)
      showed undetectable rod specific responses and electronegative maximal responses,
      but normal ISCEV cone responses. Additional S-cone specific ERG recordings were
      of reduced amplitude in all patients studied. There was no apparent rod component
      to the dark adaptation curve. Central 30 degrees thresholds were normal under
      photopic conditions but showed increased thresholds under scotopic conditions for
      both red and blue stimuli. CONCLUSION: Results from investigation of this family
      are consistent with an impairment of rod photoreceptor signalling. The ERG
      findings suggest an abnormality occurring after phototransduction with rod and S
      cone pathway involvement. These findings differ from those rare families reported
      previously with dominant CSNB.

PMID- 15258018
TI  - Efficacy of core vitrectomy preceding triple corneal procedure.
AB  - AIMS: To evaluate the effectiveness of core vitrectomy preceding triple corneal
      procedure (penetrating keratoplasty, extracapsular cataract extraction, and
      intraocular lens (IOL) implantation). METHODS: Thirty one consecutive eyes of 31
      patients with indication for triple corneal procedure were randomly assigned to
      either triple procedure with core vitrectomy (vitrectomy group) or without
      vitrectomy (control group). The success rate of IOL implantation, IOL
      positioning, intraoperative and postoperative complications, endothelial cell
      loss, and best corrected visual acuity (BCVA) were compared. Follow up period was
      six months. Factors that may contribute to vitreous pressure elevation were also
      investigated in each case. RESULTS: There was no statistically significant
      difference in each clinical parameter examined except a tendency of facilitating
      IOL implantation (p = 0.11). There were two cases of vitreous loss in the control
      group. Retinal detachment was not seen in any of the cases. The body mass index
      and age were related to higher vitreous pressure (p<0.05). CONCLUSION: Core
      vitrectomy preceding triple corneal procedure is not necessary for all cases.

PMID- 15258019
TI  - Effect of haemodialysis on retinal circulation in patients with end stage renal
      disease.
AB  - AIMS: To investigate the effect of haemodialysis on retinal circulation in
      patients with end stage renal disease (ESRD). METHOD: Seventeen consecutive
      patients with ESRD were recruited into the study. The authors simultaneously
      measured changes in vessel diameter and blood velocity and calculated the retinal
      blood flow (RBF) in the retinal veins in patients with ESRD before and after
      haemodialysis using a laser Doppler velocimetry system. In addition, the
      relations between the changes in systemic and retinal circulatory parameters were
      examined. RESULTS: There was a group averaged increase in vessel diameter (p =
      0.003) after haemodialysis. However, the blood velocity and RBF values obtained
      after haemodialysis were not significantly different from those before
      haemodialysis (p = 0.66 and p = 0.63, respectively). The changes in vessel
      diameter were negatively (r = -0.549, p = 0.02) correlated with the change in
      MABP, but the changes in blood velocity and RBF were positively correlated with
      the change in MABP (r = 0.683, p<0.002 and r = 0.589, p<0.01, respectively). The
      change in RBF was also inversely correlated with the increase in haematocrit (r =
      -0.693, p<0.002) and the amount of fluid removed (r = -0.597, p<0.01).
      CONCLUSION: The results indicate that haemodialysis and the associated changes in
      systemic circulatory parameters may affect the retinal circulation in patients
      with ESRD.

PMID- 15258020
TI  - A newly developed peripheral anterior chamber depth analysis system: principle,
      accuracy, and reproducibility.
AB  - AIM: To develop a new, non-contact system for measuring anterior chamber depth
      (ACD) quantitatively, and to investigate its accuracy as well as interobserver
      and intraobserver reproducibility. METHODS: The system scanned the ACD from the
      optical axis to the limbus in approximately 0.5 second and took 21 consecutive
      slit lamp images at 0.4 mm intervals. A computer installed program automatically
      evaluated the ACD, central corneal thickness (CT), and corneal radius of
      curvature (CRC) instantly. A dummy eye was used for investigating measurement
      accuracy. The effects of CT and CRC on the measurement results were examined
      using a computer simulation model to minimise measurement errors. Three examiners
      measured the ACD in 10 normal eyes, and interobserver and intraobserver
      reproducibility was analysed. RESULTS: The ACD values measured by this system
      were very similar to theoretical values. Increase of CRC and decrease in CT
      decreased ACD and vice versa. Data calibration using evaluated CT and CRC
      successfully reduced measurement errors. Intraobserver and interobserver
      variations were small. Their coefficient variation values were 7.4% (SD 2.3%) and
      6.7% (0.7%), and these values tended to increase along the distance from the
      optical axis. CONCLUSION: The current system can measure ACD with high accuracy
      as well as high intraobserver and interobserver reproducibility. It has potential
      use in measuring ACD quantitatively and screening subjects with narrow angle.

PMID- 15258021
TI  - Quantitative evaluation of changes in anterior segment biometry by peripheral
      laser iridotomy using newly developed scanning peripheral anterior chamber depth
      analyser.
AB  - AIM: Using the newly developed scanning peripheral anterior chamber depth
      analyser (SPAC), the effects of peripheral laser iridotomy (PLI) on peripheral
      anterior chamber depth (PACD) were determined quantitatively as was the
      association between PACD and chronic elevation of intraocular pressure (IOP)
      after PLI. METHODS: 16 eyes of 15 patients with acute primary angle closure
      glaucoma (PACG) attack, 14 eyes of 14 patients with narrow angle and PACG attack
      in their fellow eyes, and 13 eyes of seven patients with chronic angle closure
      glaucoma (CACG) were enrolled. The SPAC scanned the anterior ocular segment from
      the optical axis to the limbus and took 21 consecutive slit lamp images at 0.4 mm
      intervals. A computer installed program automatically evaluated the PACD and the
      averaged values of three measurements were employed for analysis. RESULTS: PLI
      significantly increased PACD and changed the iris contour from convex to flat or
      concave in all the enrolled eyes. The extent of the PLI induced PACD increase was
      enhanced with increasing distance from the optical axis. Comparing PACDs after
      PLI, eyes that received prophylactic PLI showed the greatest extent of PLI
      induced PACD increase, followed by eyes with CACG and eyes with PACG attack. The
      PACD of eyes with PACG attack was almost the same as that of the fellow eyes of
      PACG attack before prophylactic PLI. Eyes with PACG attack showed poorer IOP
      control after PLI than eyes with narrow angle and CACG with PLI. CONCLUSIONS: PLI
      significantly increases PACD and the small PLI induced opening of PACD may
      contribute to chronic IOP elevation after PLI.

PMID- 15258022
TI  - The Auckland Cataract Study: 2 year postoperative assessment of aspects of
      clinical, visual, corneal topographic and satisfaction outcomes.
AB  - AIM: To assess clinical, visual, computerised corneal topographic, and subjective
      satisfaction with visual acuity, in a cohort of subjects 2 years after
      phacoemulsification surgery in a public hospital in New Zealand. METHODS:
      Prospective study of a representative sample of 97 subjects (20%) randomly
      selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort.
      The clinical assessment protocol was identical to the ACS and included an
      extensive questionnaire to enable direct comparisons to be made between the two
      groups. RESULTS: The study population was predominantly female (66%) with a mean
      age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and
      10.3% of subjects respectively, and 10.3% required referral to either a general
      practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected
      visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with
      mean spherical equivalent -0.37 (1.01) dioptres (D) and astigmatism -1.07 (0.70)
      D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5
      Snellen equivalent), spherical equivalent -0.59 (1.07) D, and astigmatism -1.14
      (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or
      better, irrespective of pre-existing ocular disease. The overall posterior
      capsule opacification (PCO) rate was 20.4% and this was visually insignificant in
      all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy.
      Orbscan II elevation technology demonstrated corneal stability 2 years after
      uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in
      approximately half of the subjects 1 month postoperatively, astigmatism showed a
      tendency to regress towards the preoperative level with local corneal thickening
      at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had
      undergone cataract surgery. Overall, 75.3% of subjects were moderately to very
      satisfied with their current level of visual acuity. CONCLUSION: Two years after
      cataract surgery subjects are generally satisfied with their current level of
      vision and distance BSCVA is 6/12 or better in the majority of eyes. Although
      only a minority of eyes develop sufficient PCO to require capsulotomy 10.3% of
      eyes develop new vision threatening ocular pathology.

PMID- 15258023
TI  - Retinal blood flow measurements and neuroretinal rim damage in glaucoma.
AB  - AIM: To assess retinal blood flow characteristics in subjects with normal tension
      glaucoma (NTG), primary open angle glaucoma (POAG), and a group of controls using
      the Heidelberg retina flowmeter (HRF). The vascular parameters were correlated
      against structural damage of the optic nerve head, assessed using the Heidelberg
      retina tomograph (HRT). METHODS: HRF images were obtained in 76 subjects with
      NTG, 58 with POAG, and 38 controls. Optic nerve head images, acquired using the
      HRT, were analysed with Moorfields Regression Analysis software. The HRF
      variables, measured adjacent to a rim segment identified as "abnormal," were
      compared with the vascular parameters of the "normal" rim segments. The HRF
      parameters of the segments identified as normal in glaucoma subjects were
      compared with matched control segments. RESULTS: The glaucoma subjects had
      significantly lower retinal haemodynamics than the control subjects. There were
      no significant differences in the HRF parameters between the NTG and POAG
      subjects. The discs that had been identified as having abnormal segments had
      lower HRF values than those with a corresponding normal segment. The glaucoma
      subjects with normal rim segments had statistically significant lower velocity,
      flow, and volume measurements than the controls for each location sampled.
      CONCLUSION: This study shows a relation between structural damage of the optic
      nerve head and the level of retinal blood flow. The changes in the circulation
      could indicate that it may be an early marker of the pathological process.

PMID- 15258024
TI  - Indocyanine green mediated photothrombosis for the management of predominantly
      classic choroidal neovascularisation caused by age related macular degeneration.
AB  - AIMS: To study the effectiveness of indocyanine green mediated photothrombosis in
      the management of predominantly classic subfoveal choroidal neovascularisation
      associated with age related macular degeneration. METHODS: Prospective, non
      comparative, interventional case series of nine patients with predominantly
      classic subfoveal choroidal neovascularisation secondary to age related macular
      degeneration who declined photocoagulation or verteporfin photodynamic therapy.
      Patients were submitted to one or more treatments with an intravenous injection
      of a small volume of high concentration indocyanine green solution followed by
      low irradiance, large spot 810 nm continuous laser application via a
      transpupillary approach. Main outcome measures were change in best corrected
      visual acuity and macular exudative manifestations. RESULTS: After 12 months of
      follow up, the final best corrected visual acuity was the same (plus or minus two
      ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes
      (33%), and worsened by more than two lines in the remaining eye. The improved
      vision was probably related to partial or complete restoration of the macular
      architecture as a result of fluid resolution, whereas the worsened vision was
      primarily the result of treatment failure in achieving substantial choroidal
      neovascular occlusion. There were no complications related to the procedure.
      CONCLUSION: Indocyanine green mediated photothrombosis may be an effective
      alternative treatment for predominantly classic subfoveal choroidal
      neovascularisation caused by age related macular degeneration.

PMID- 15258025
TI  - Alteration of choroidal circulation in the foveal region in patients with type 2
      diabetes.
AB  - AIM: To investigate changes in choroidal blood flow (CBF) in the foveal region in
      patients with type 2 diabetes. METHODS: Laser Doppler flowmetry was used to
      determine the CBF in the foveal region in 70 patients with type 2 diabetes and 36
      age and sex matched healthy subjects (control group). The patients were
      classified into three groups: 33 patients (33 eyes) with no diabetic retinopathy
      (NDR), 20 patients (20 eyes) with non-proliferative diabetic retinopathy and no
      macular oedema (NPDR/MO-), and 17 patients (17 eyes) with NPDR and MO (NPDR/MO+).
      Optical coherence tomography was also used to measure the foveal thickness.
      RESULTS: The group averaged CBF values were 13.5 (4.9), 9.4 (2.5), 10.8 (4.8),
      and 5.6 (2.0) (arbitrary units) in the control, NDR, NPDR/MO-, and NPDR/MO+
      groups, respectively. The group averaged CBF values in the NDR group decreased
      (30.2%; p<0.01) compared with the control group. The average CBF value in the
      NPDR/MO+ group was also significantly lower (48.2%; p<0.01) compared with that in
      the NPDR/MO- group. CONCLUSION: The CBF in the foveal region significantly
      decreases in patients with diabetes, especially those with macular oedema.

PMID- 15258026
TI  - Risk evaluation of outcome of vitreous surgery for proliferative diabetic
      retinopathy based on vitreous level of vascular endothelial growth factor and
      angiotensin II.
AB  - AIMS: To ascertain whether measurement of the vitreous fluid levels of vascular
      endothelial growth factor (VEGF) or angiotensin II (Ang II) could predict the
      outcome of vitreous surgery in patients with proliferative diabetic retinopathy
      (PDR). METHODS: A prospective observational case study was performed in 61
      consecutive patients (61 eyes) with PDR who underwent vitreoretinal surgery.
      Vitreous fluid samples were obtained during surgery. The VEGF level in vitreous
      fluid and plasma was determined by enzyme linked immunosorbent assay, while the
      Ang II level was measured by radioimmunoassay. Patients were prospectively
      followed for 6 months and the postoperative outcome was analysed by logistic
      regression analysis. RESULTS: No improvement and/or progression of PDR was seen
      in 15 (25%) of the 61 eyes. Vitreous levels of VEGF and Ang II were significantly
      higher in eyes with progression of PDR than in eyes with regression of PDR (p =
      0.0044, and p = 0.0178, respectively). Multivariate logistic regression analysis
      showed that the vitreous VEGF level increased along with the progression of PDR
      after vitreous surgery (odds ratio 2.48, p = 0.0008). CONCLUSION: A high vitreous
      fluid VEGF level is associated with a significant risk of postoperative
      progression of PDR. The vitreous level of VEGF at the time of surgery may be a
      useful predictor of the outcome.

PMID- 15258027
TI  - Retinoblastoma patients with high risk ocular pathological features: who needs
      adjuvant therapy?
AB  - AIMS: To describe the outcome of patients with non-metastatic unilateral
      retinoblastoma with high risk histopathological features after primary
      enucleation, and to clarify the need and results of adjuvant therapy. PATIENTS
      AND METHODS: From 1980 to 2001 adjuvant therapy was recommended only to patients
      with scleral involvement, post-laminar optic nerve involvement (PLONI) with
      either a positive margin or associated choroidal involvement, or (before 1994)
      isolated PLONI. RESULTS: 108 of 224 patients had at least one high risk feature
      (choroidal, scleral, anterior chamber, and/or PLONI). Patients with isolated
      choroidal (n = 55) or anterior chamber (n = 2) invasion, and most with PLONI
      without other risk factors (n = 21) were not treated; three relapsed but are long
      term survivors after intensive therapy. Four with isolated PLONI received
      adjuvant chemotherapy and none relapsed. Three of 11 with PLONI and concomitant
      choroidal or scleral involvement who received adjuvant therapy relapsed, versus
      two of four not treated. Two of five with scleral disease relapsed. All 12 with
      cut end involvement received adjuvant treatment and none relapsed. In the total
      group, all four patients who relapsed after adjuvant therapy died. CONCLUSIONS:
      Relapsing patients can be rescued with intensive therapy. Those with isolated
      choroidal or PLONI have a good prognosis without adjuvant therapy. Patients with
      PLONI with a positive margin have a good prognosis if treated with combined
      therapy. Those with scleral involvement or PLONI with concomitant choroid disease
      may benefit from adjuvant therapy.

PMID- 15258028
TI  - A multicentre report from the Mexican Retinoblastoma Group.
AB  - BACKGROUND: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The
      incidence of retinoblastoma in Mexico is probably higher than the incidence
      reported worldwide, however there is not enough information about the
      characteristics of this illness in Mexico. This report aims to present the
      results of a multicentre clinical survey of RB in Mexico. METHODS: A
      retrospective study was carried out on all RB cases treated in 16 institutions
      during the last six years. The variables analysed were age at diagnosis, sex,
      affected eyes, treatment modalities, and pathological staging. Overall survival
      was obtained. RESULTS: The authors analysed 500 cases; age range was 0-182
      months. There were 364 unilateral cases (72.8%). Enucleation was performed in
      84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II,
      18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data.
      Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at
      73 months follow up. CONCLUSIONS: The paper presents a great number of cases and
      pioneers multicentre studies in paediatric ophthalmology and oncology in this
      country. Given the great number of patients in advanced stages and the
      variability on treatment schemes, it is evident that it is mandatory to work in a
      cooperative group and develop a national early detection programme as well as a
      treatment protocol which include all specialists involved in the care of patients
      with RB.

PMID- 15258029
TI  - Effects of melatonin on the nitric oxide treated retina.
AB  - AIMS: Nitric oxide (NO) is a free radical which reportedly causes damage to
      living cells. This study evaluated the damaging effect of NO and the protection
      of melatonin on the retina in vivo. METHODS: Female Wistar rats (230-250 g)
      received two intraperitoneal injections of either melatonin (5 mg/kg) or vehicle
      alone. After general anaesthesia, the animals received 1 microl intravitreal
      injections of 0.9% saline and 1 mM sodium nitroprusside (SNP) into the right eye
      and the left eye, respectively. The animals were divided into two groups and then
      sacrificed after 24 hours (day 1) and 96 hours (day 4). The mean inner retinal
      layer thickness (mIRLT), the number of retinas expressing hyperchromatic (HC)
      nuclei in the inner nuclear layer (INL) and the apoptotic ganglion cell detection
      were compared. RESULTS: After 1 day, SNP significantly increased the mIRLT by 45%
      (p = 0.004), initiated more INL nuclear HC expression (p = 0.01) and apoptotic
      nuclei (p<0.05) compared with the control eyes. Injection of melatonin
      ameliorated these changes. On day 4, SNP demonstrated similar effects in all
      parameters on the retina. After the injection of melatonin, both INL HC
      expression and apoptotic ganglion nuclei in the SNP treated eyes were similar to
      the controls but the mIRLT was significantly greater than in controls (p =
      0.006). CONCLUSION: Uncontrolled NO elevation caused morphological and nuclear
      changes in the retina. Melatonin significantly suppressed the NO induced increase
      in mIRLT, INL HC expression, and apoptotic ganglion cells on day 1, but not after
      day 4. Melatonin may have a protective role in the NO elevated retina.

PMID- 15258030
TI  - Differential expression of connective tissue growth factor in microglia and
      pericytes in the human diabetic retina.
AB  - BACKGROUND/AIM: Connective tissue growth factor (CTGF) stimulates extracellular
      matrix formation, fibrosis, and angiogenesis. It has a role in the pathogenesis
      of diabetic nephropathy and possibly in diabetic retinopathy (DR): in cultured
      retinal vascular cells CTGF is induced by VEGF-A. To further characterise this
      role the authors investigated CTGF expression in normal and diabetic human
      retina. METHODS: CTGF expression patterns were studied by immunohistochemistry in
      the retina of eyes of 36 diabetic persons and 18 non-diabetic controls and
      compared with markers of endothelial cells (CD31, PAL-E), pericytes (NG2),
      astrocytes (GFAP), and microglia (CD45). RESULTS: In the retina, distinct and
      specific staining of CTGF was observed in microglia, situated around or in close
      vicinity of retinal capillaries. In the control cases, sporadic staining of
      pericytes was also observed within the vascular wall. In contrast, in the retina
      of people with diabetes, CTGF staining in microglia was decreased and staining in
      pericytes was increased. This pattern of predominantly pericyte staining was
      observed in 20 out of 36 diabetic cases and in one out of 18 controls. The
      altered CTGF staining patterns in the diabetic cases did not correlate to
      staining of PAL-E, a marker of retinal vascular leakage associated with DR.
      CONCLUSIONS: The study shows that CTGF is expressed in microglia in the normal
      retina whereas in a large subset of diabetic persons, CTGF expression shifts to
      microvascular pericytes. This altered CTGF expression pattern appears unrelated
      to manifest DR and may therefore represent a preclinical retinal change caused by
      diabetes. The results suggest a distinct, but as yet unidentified, role of CTGF
      in the pathogenesis of diabetic retinopathy.

PMID- 15258032
TI  - Orbital varices and orbital wall defects.

PMID- 15258031
TI  - Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic
      anhydrase inhibition and carbon dioxide breathing.
AB  - BACKGROUND/AIMS: Prostaglandins are important in blood flow regulation. Carbon
      dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen
      tension in the retina and optic nerve. To study the mechanism of this effect and
      the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension
      (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the
      ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in
      the pig. METHODS: Optic nerve oxygen tension was measured in 11 pigs with a
      polarographic oxygen electrode. The tip of the electrode was placed 0.5 mm above
      the optic disc. The effects of indomethacin, CO(2) breathing (3%) before and
      after indomethacin treatment, and carbonic anhydrase inhibition with or without
      indomethacin treatment were investigated. RESULTS: Administration of 300 mg
      indomethacin decreased optic nerve oxygen tension significantly. Carbonic
      anhydrase inhibition and CO(2) breathing increased ONPO(2) significantly. After
      indomethacin had been given, the rise in ONPO(2) caused by CO(2) breathing and
      carbonic anhydrase inhibition was significantly reduced. CONCLUSION: Systemic
      administration of indomethacin decreases the optic nerve oxygen tension; this is
      probably the result of decreased blood flow through vasoconstriction of vessels
      in the optic nerve. Additionally, indomethacin diminishes the ONPO(2) increasing
      effect of CO(2) breathing and carbonic anhydrase inhibition, thus affecting the
      reactivity of vessels in the optic nerve.

PMID- 15258033
TI  - Exenteration of invasive conjunctival squamous cell carcinoma.

PMID- 15258034
TI  - Familial pseudotumoral sclerochoroidal calcification associated with
      chondrocalcinosis.

PMID- 15258035
TI  - Whole body PET/CT imaging for detection of metastatic choroidal melanoma.

PMID- 15258036
TI  - Trans-Tenon's retrobulbar triamcinolone infusion for small choroidal
      neovascularisation.

PMID- 15258037
TI  - Retinoblastoma in a child conceived by in vitro fertilisation.

PMID- 15258038
TI  - Angle closure glaucoma after laser photocoagulation for retinopathy of
      prematurity.

PMID- 15258039
TI  - Sequential treatment of central retinal vein occlusion with intravitreal tissue
      plasminogen activator and intravitreal triamcinolone.

PMID- 15258040
TI  - Severe post-laser suprachoroidal haemorrhaging in a diabetic patient receiving
      anticoagulants.

PMID- 15258041
TI  - Accurate placement of corticosteroids into the sub-Tenon's space provides good
      drug penetration into the eye.

PMID- 15258042
TI  - Owls' eyes move.

PMID- 15258043
TI  - Combating HIV/AIDS in developing countries.

PMID- 15258044
TI  - Compulsion and psychiatry--the role of advance statements.

PMID- 15258045
TI  - Spiritual needs in health care.

PMID- 15258046
TI  - New treatments for colon cancer.

PMID- 15258047
TI  - Getting ethics into practice.

PMID- 15258049
TI  - Thailand ignores HIV epidemic in drug users.

PMID- 15258052
TI  - Developing economies shrink as AIDS reduces workforce.

PMID- 15258053
TI  - WHO insists it can meet its target for antiretrovirals by 2005.

PMID- 15258054
TI  - France bans reproductive and therapeutic cloning.

PMID- 15258061
TI  - New penalties proposed for Dutch doctors who flout euthanasia law.

PMID- 15258062
TI  - MRSA infections rose by 5% between 2003 and 2004.

PMID- 15258065
TI  - 15th International AIDS conference: New grassroots organisation is set up to
      tackle AIDS.

PMID- 15258063
TI  - US medical students in Cuba receive temporary reprieve.

PMID- 15258068
TI  - Stronger sanctions needed against companies that suppress data.

PMID- 15258069
TI  - Mumps cases rise among teenagers and young adults.

PMID- 15258070
TI  - Eradication of methicillin resistant Staphylococcus aureus by "ring fencing" of
      elective orthopaedic beds.
AB  - PROBLEM: Deep infection after joint arthroplasty can be catastrophic, leading to
      further surgery, loss of the prosthesis, disability, and risk of mortality.
      Twenty nine new cases of methicillin resistant Staphylococcus aureus occurred in
      the first year after elective orthopaedic surgery was centralised to a district
      general hospital in Essex. DESIGN: Prospective trial to establish whether ring
      fencing of elective orthopaedic beds and introduction of simple infection control
      measures has an effect on the rates of postoperative infections and number of
      patients treated. PARTICIPANTS AND SETTING: All patients undergoing primary hip
      or knee replacement in a district general hospital in Essex, England, between
      July 1999 and July 2001. MAIN MEASURES FOR IMPROVEMENT: Number of patients having
      joint replacement; number of all postoperative infections in the participant
      group; number of cases of methicillin resistant Staphylococcus aureus. STRATEGIES
      FOR CHANGE: Ring fencing of the elective orthopaedic ward and introduction of
      simple infection control measures. EFFECTS OF CHANGE: The incidence of all
      postoperative infections decreased from 43/417 to 15/488 (P < 0.0001), with no
      new cases of methicillin resistant Staphylococcus aureus. LESSONS LEARNT: The
      introduction of a ring fenced elective orthopaedic ward and simple infection
      control measures allowed 17% more patients to be treated and significantly
      reduced the incidence of all postoperative infections.

PMID- 15258071
TI  - Threatened miscarriage: evaluation and management.

PMID- 15258072
TI  - Musculoskeletal pain in female asylum seekers and hypovitaminosis D3.

PMID- 15258073
TI  - Management of burn injuries of various depths.

PMID- 15258076
TI  - Genetic information: a joint account?

PMID- 15258077
TI  - Diagnostic tests 4: likelihood ratios.

PMID- 15258078
TI  - Sentinel lymph node biopsy: optimum method remains to be determined.

PMID- 15258079
TI  - Sentinel lymph node biopsy: not yet standard of care for melanoma.

PMID- 15258080
TI  - Sentinel lymph node biopsy: sentinel node technique has drawbacks.

PMID- 15258081
TI  - Review of instruments for peer assessment of physicians: clinics with peers keep
      you on the straight and narrow...

PMID- 15258082
TI  - Ginkgo biloba and acetazolamide for acute mountain sickness: exclusion of high
      risk, low status groups perpetuates discrimination and inequalities.

PMID- 15258083
TI  - Review of instruments for peer assessment of physicians: ...and our impact on one
      another is important.

PMID- 15258084
TI  - Ginkgo biloba and acetazolamide for acute mountain sickness: bias in participants
      may underestimate effectiveness of agents.

PMID- 15258085
TI  - National screening programme for chlamydia exists in England.

PMID- 15258086
TI  - Discharge rates for suspected acute coronary syndromes: is morbidity or
      empowerment increasing?

PMID- 15258087
TI  - Discharge rates for suspected acute coronary syndromes: clinical assessment tools
      need improving.

PMID- 15258088
TI  - Tracking system for studies should be in place.

PMID- 15258089
TI  - Prisons show prophylaxis for close contacts may indeed help in next flu pandemic.

PMID- 15258090
TI  - Emergent human pathogen simian virus 40 and its role in cancer.
AB  - The polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which
      induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in
      laboratory animals. Persuasive evidence now indicates that SV40 is causing
      infections in humans today and represents an emerging pathogen. A meta-analysis
      of molecular, pathological, and clinical data from 1,793 cancer patients
      indicates that there is a significant excess risk of SV40 associated with human
      primary brain cancers, primary bone cancers, malignant mesothelioma, and non
      Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be
      functionally important in the development of some of those human malignancies.
      Therefore, the major types of tumors induced by SV40 in laboratory animals are
      the same as those human malignancies found to contain SV40 markers. The Institute
      of Medicine recently concluded that "the biological evidence is of moderate
      strength that SV40 exposure could lead to cancer in humans under natural
      conditions." This review analyzes the accumulating data that indicate that SV40
      is a pathogen which has a possible etiologic role in human malignancies. Future
      research directions are considered.

PMID- 15258092
TI  - Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging
      diagnosis.
AB  - Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in
      East Asia. A large and compelling body of evidence links clonorchiasis and
      cholangiocarcinoma, although the mechanisms involved are not completely
      understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia,
      and this could facilitate at least one stage of the carcinogenesis, which is
      promoting effect. In areas of endemic infection, more clonorchiasis cases are now
      diagnosed incidentally during radiological examinations such as cholangiography,
      ultrasonography, and computed tomography. Radiological findings are regarded as
      pathognomonic for clonorchiasis since they reflect the unique pathological
      changes of this disorder. These radiological examinations currently play
      important roles in the diagnosis, staging, and decision-making process involved
      in the treatment of cholangiocarcinoma. The morphological features and
      radiological findings of clonorchiasis-associated cholangiocarcinoma are
      essentially combinations of the findings for the two diseases. The morphological
      features of clonorchiasis- associated cholangiocarcinoma, observed in
      radiological examinations, do not differ from those of the usual
      cholangiocarcinoma. In patients diagnosed with or suspected to have
      clonorchiasis, radiological findings should be carefully scrutinized for occult
      cholangiocarcinoma.

PMID- 15258093
TI  - Emerging from obscurity: biological, clinical, and diagnostic aspects of
      Dientamoeba fragilis.
AB  - Ever since its first description in 1918, Dientamoeba fragilis has struggled to
      gain recognition as a significant pathogen. There is little justification for
      this neglect, however, since there exists a growing body of case reports from
      numerous countries around the world that have linked this protozoal parasite to
      clinical manifestations such as diarrhea, abdominal pain, flatulence, and
      anorexia. A number of studies have even incriminated D. fragilis as a cause of
      irritable bowel syndrome, allergic colitis, and diarrhea in human
      immunodeficiency virus patients. Although D. fragilis is most commonly identified
      using permanently stained fecal smears, recent advances in culturing techniques
      are simplifying as well as improving the ability of investigators to detect this
      organism. However, there are limitations in the use of cultures since they cannot
      be performed on fecal samples that have been fixed. Significant progress has been
      made in the biological classification of this organism, which originally was
      described as an ameba. Analyses of small-subunit rRNA gene sequences have clearly
      demonstrated its close relationship to Histomonas, and it is now known to be a
      trichomonad. How the organism is transmitted remains a mystery, although there is
      some evidence that D. fragilis might be transmitted via the ova of the pinworm,
      Enterobius vermicularis. Also, it remains to be answered whether the two distinct
      genotypes of D. fragilis recently identified represent organisms with differing
      virulence.

PMID- 15258094
TI  - Rapid diagnosis of pharyngitis caused by group A streptococci.
AB  - Although commercial rapid antigen detection tests (RADTs) are more expensive than
      blood agar plate (BAP) cultures, the advantage they offer is the speed with which
      they provide results. Rapid identification and consequent prompt treatment of
      patients with pharyngitis due to group A beta-hemolytic streptococci (GABHS) can
      reduce the risk of spread of GABHS, can allow patients to return to school or
      work sooner, and may reduce the acute morbidity of this illness. In most studies,
      RADTs have been compared with BAP cultures as the criterion standard. However,
      these comparisons are complicated by the fact that there is no universally
      accepted procedure for performing a BAP culture. The great majority of the RADTs
      that are currently available have a high specificity (i.e., 95% or greater) and a
      sensitivity of between 70 and 90% compared with BAP cultures. Few published
      studies have compared the performance of various RADTs to each other or examined
      the performance of various RADTs in the office setting. There is also relatively
      little published information about how physicians in practice actually use RADTs,
      but the available information suggests that many physicians do not follow
      recommended guidelines. While the development of easy-to-perform RADTs for the
      diagnosis of GABHS pharyngitis has altered clinical practice substantially, only
      limited data about cost-effectiveness are currently available.

PMID- 15258091
TI  - Pathogenesis of malaria and clinically similar conditions.
AB  - There is now wide acceptance of the concept that the similarity between many
      acute infectious diseases, be they viral, bacterial, or parasitic in origin, is
      caused by the overproduction of inflammatory cytokines initiated when the
      organism interacts with the innate immune system. This is also true of certain
      noninfectious states, such as the tissue injury syndromes. This review discusses
      the historical origins of these ideas, which began with tumor necrosis factor
      (TNF) and spread from their origins in malaria research to other fields. As well
      the more established proinflammatory mediators, such as TNF, interleukin-1, and
      lymphotoxin, the roles of nitric oxide and carbon monoxide, which are chiefly
      inhibitory, are discussed. The established and potential roles of two more
      recently recognized contributors, overactivity of the enzyme poly(ADP-ribose)
      polymerase 1 (PARP-1) and the escape of high-mobility-group box 1 (HMGB1) protein
      from its normal location into the circulation, are also put in context. The
      pathogenesis of the disease caused by falciparum malaria is then considered in
      the light of what has been learned about the roles of these mediators in these
      other diseases, as well as in malaria itself.

PMID- 15258096
TI  - Therapy of falciparum malaria in sub-saharan Africa: from molecule to policy.
AB  - The burden of falciparum malaria remains as great as ever, and, as has probably
      always been the case, it is carried mainly by tropical Africa. Of the various
      means available for the control of malaria, the use of effective drugs remains
      the most important and is likely to remain so for a considerable time to come.
      Unfortunately, the extensive development of resistance by the parasite threatens
      the utility of most of the affordable classes of drug: the development of novel
      antimalarials has never been more urgently needed. Any attempt to understand the
      vast complexities of falciparum malaria in Africa requires an ability to think
      "from molecule to policy." In consequence, the review ambitiously tries to
      examine the current pharmacopeia, the process by which new drugs are developed
      and the ways in which drugs are actually used, in both the formal and informal
      health sectors. The informal sector is particularly important in Africa, where
      around half of all antimalarial treatments are bought from informal outlets and
      taken at home without supervision by health care professionals: the potential
      impact of adherence on clinical outcome is discussed. Given that the full costs
      are carried by the patient in a large proportion of cases, the importance of drug
      affordability is explored. The review also discusses the splicing of new drugs
      into national policy. The various parameters that feed into deliberations on
      changes in drug policy are discussed.

PMID- 15258098
TI  - Competency assessment in the clinical microbiology laboratory.
AB  - The laboratory comprises an invaluable part of the total health care provided to
      patients. Competency assessment is one method by which we can verify that our
      employees are competent to perform laboratory testing and report accurate and
      timely results. To derive the greatest benefit from the inclusion of competency
      assessment in the laboratory, we must be sure that we are addressing areas where
      our efforts can be best utilized to optimize patient care. To be competent, an
      employee must know how to perform a test, must have the ability to perform the
      test, must be able to perform the test properly without supervision, and know
      when there is a problem with the test that must be solved. In some cases,
      competency assessment protocols may demonstrate areas of competence but can fail
      to disclose incompetence. For example, challenges of low-complexity tasks (such
      as reading the technical procedure manual) are inferior to challenges that
      measure understanding and execution of a protocol, and poorly designed competency
      challenges will probably not detect substandard laboratory performance. Thus, if
      we are to receive the greatest benefit from our competency assessment programs,
      which may be time-consuming for the supervisors and the staff as well, we must
      not only meet the letter of the law but also find a way to make these assessments
      meaningful, instructive, and able to detect areas of concern. As we address
      competency assessment in our laboratories, we must understand that when done
      properly, competency assessment will reward our organizations and assist us in
      providing the best possible care to our patients.

PMID- 15258099
TI  - The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the
      effects of naturally occurring variants.
AB  - Mycophenolic acid (MPA), a standard immunosuppressive drug, is characterized by
      unexplained highly variable pharmacokinetics in transplant recipients. The
      primary metabolic pathway of MPA is glucuronidation; however, literature reports
      are inconsistent and the contribution of all human UDP-glucuronosyltransferases
      (UGTs) has never been systematically assessed. Sixteen heterologously expressed
      UGTs were studied for MPA 7-O-glucuronidation and compared with liver, kidney,
      and intestine microsomes. For direct measurement of MPA and mycophenolic acid 7-O
      glucuronide (MPAG), we used a liquid chromatography-mass spectrometry protocol.
      Metabolic studies demonstrated that the glucuronidation of MPA in humans occurs
      mainly in the liver at variable rates, as well as in the kidney and the
      intestine. Kinetic data normalized for UGT expression levels point to 1A8 and 1A9
      as the main UGTs, as well as to low-activity enzymes, 1A1, 1A7, and 1A10.
      According to their expression profiles, 1A8 and 1A9 are proposed, respectively,
      as the main extra-hepatic and the only hepatic enzymes involved. The effects of
      naturally occurring 1A8 ((*)2 and (*)3) and 1A9 ((*)2 and (*)3) variants on MPA 7
      O-glucuronidation were studied and data suggest that the C(277)Y of 1A8 and the
      M(33)T of 1A9 may influence MPAG levels. A number of low-activity alleles were
      also identified in 1A1 [(*)6 (G(71)R), (*)7 (Y(486)D), (*)27 (P(229)Q), and (*)35
      (L(233)R)], 1A7 [(*)3 (K(129)K(131)R(208)), (*)4 (R(208)), (*)5 (S(115)), (*)8
      (K(129)K(131)D(139)R(208)), and (*)9 (S(115)K(129)K(131))], and 1A10 [(*)2
      (E(139)K)]. Our study provides preliminary evidences that genetic factors,
      especially in the hepatic UGT1A9, may contribute to the variability of MPA
      pharmacokinetics observed in transplant patients.

PMID- 15258101
TI  - Insect repellent [correction of repellant] interactions: sunscreens enhance DEET
      (N,N-diethyl-m-toluamide) absorption.
AB  - Toxicology studies are typically performed on single compounds, which we
      hypothesized would miss adverse synergies from chemical mixtures. This hypothesis
      was tested using an insect repellant and sunscreens because both groups include
      known permeation enhancers, with prior pediatric reports of toxicity from highly
      concentrated DEET (N,N-diethyl-m-toluamide). Using real-time mass spectroscopy in
      a hairless mouse skin model, we confirmed substantial penetration of a 20% DEET
      standard. Despite a lower (10%) DEET content, a commercially marketed sunscreen
      formulation had a 6-fold more rapid detection (5 versus 30 min) and 3.4-fold
      greater penetration at steady state. We also tested the efficacy of DEET
      microemulsion products and confirmed that one successfully slowed the onset of
      absorption, but not the steady-state permeation. Risks from mixtures of potential
      toxins are worthy of routine testing, which can be accomplished by simple assays,
      and are of utmost importance for pediatric applications.

PMID- 15258100
TI  - Levothyroxine up-regulates P-glycoprotein independent of the pregnane X receptor.
AB  - P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) constitute a physiologic
      barrier in the intestine for many of the same substrates. Their expression can be
      influenced by nuclear receptor NR1I2 (pregnane X receptor; PXR), which acts as a
      receptor for various endobiotics and xenobiotics. However, P-gp and CYP3A4 are
      not identical in anatomic localization, suggesting unique as well as shared
      regulatory mechanisms of gene expression. We used established human colon
      carcinoma cell lines (LS180 and Caco-2) and measured mRNA and protein levels in
      cells after exposures to levothyroxine (L-T(4)), triiodo-L-thyronine (L-T(3)),
      and rifampin. Results indicate that L-T(4), L-T(3), and rifampin can upregulate
      the expression of P-gp mRNA and protein in LS180 cells, but only L-T(4) and L
      T(3) can produce the same effect in Caco-2 cells, which are relatively lacking in
      PXR. In addition, L-T(4) and L-T(3) did not affect the expression of CYP3A4 in
      either cell line. We conclude that P-gp, but not CYP3A4, can be up-regulated by
      thyroid hormones in vitro by a PXR-independent mechanism. Considering the
      widespread prescription use of L-T(4) preparations in the older adult population,
      these results may be important for the clinical consideration of drug-drug
      interactions mediated by P-gp.

PMID- 15258095
TI  - Phase and antigenic variation in bacteria.
AB  - Phase and antigenic variation result in a heterogenic phenotype of a clonal
      bacterial population, in which individual cells either express the phase-variable
      protein(s) or not, or express one of multiple antigenic forms of the protein,
      respectively. This form of regulation has been identified mainly, but by no means
      exclusively, for a wide variety of surface structures in animal pathogens and is
      implicated as a virulence strategy. This review provides an overview of the many
      bacterial proteins and structures that are under the control of phase or
      antigenic variation. The context is mainly within the role of the proteins and
      variation for pathogenesis, which reflects the main body of literature. The
      occurrence of phase variation in expression of genes not readily recognizable as
      virulence factors is highlighted as well, to illustrate that our current
      knowledge is incomplete. From recent genome sequence analysis, it has become
      clear that phase variation may be more widespread than is currently recognized,
      and a brief discussion is included to show how genome sequence analysis can
      provide novel information, as well as its limitations. The current state of
      knowledge of the molecular mechanisms leading to phase variation and antigenic
      variation are reviewed, and the way in which these mechanisms form part of the
      general regulatory network of the cell is addressed. Arguments both for and
      against a role of phase and antigenic variation in immune evasion are presented
      and put into new perspective by distinguishing between a role in bacterial
      persistence in a host and a role in facilitating evasion of cross-immunity.
      Finally, examples are presented to illustrate that phase-variable gene expression
      should be taken into account in the development of diagnostic assays and in the
      interpretation of experimental results and epidemiological studies.

PMID- 15258102
TI  - Effects of protein calorie malnutrition on the pharmacokinetics of ketamine in
      rats.
AB  - The effect of protein calorie malnutrition (PCM) on the pharmacokinetics of
      ketamine (KET) enantiomers has been investigated. Six control and six PCM rats
      were administered 85 mg/kg racemic KET by intramuscular injection, and plasma
      concentrations of (S)- and (R)-KET, norketamine (NKET), and 5,6
      dehydronorketamine (DNK) were measured using enantioselective gas chromatography.
      Pharmacokinetic profiles were analyzed using standard noncompartmental and
      compartmental modeling methods. The volumes of distribution were similar between
      control and PCM rats for (S)- and (R)-KET. However, total clearance of both KET
      enantiomers was decreased, resulting in an increase in systemic exposure (p <
      0.05). The KET absorption rate was also increased in PCM rats. A decrease in the
      clearance of both NKET enantiomers led to a significant increase in exposure in
      PCM rats (p < 0.005), and modeling results could not exclude the possibility that
      PCM induced an increase in the fraction of KET following the NKET pathway, which
      may further contribute to this increase in exposure. An increase in exposure to
      DNK enantiomers was also evident in PCM animals compared with controls [p < 0.005
      (DNK1); N.S. (DNK2)], which was in concordance with the decrease in apparent
      clearance values. These results show that PCM significantly alters the
      pharmacokinetics of KET and several of its metabolites.

PMID- 15258103
TI  - The hepatic pharmacokinetics of doxorubicin and liposomal doxorubicin.
AB  - To determine the role of the hepatic sinusoidal endothelium in the hepatic
      disposition of liposomal doxorubicin, we compared the hepatic pharmacokinetics of
      doxorubicin hydrochloride and the pegylated, liposomal formulation of doxorubicin
      (Caelyx). The multiple indicator-dilution technique and electron microscopy were
      used to study the disposition of doxorubicin and liposomal doxorubicin in the rat
      liver. Doxorubicin had a volume of distribution 1.56 +/- 0.45 times greater than
      that of the extracellular marker, sucrose, whereas liposomal doxorubicin had a
      volume of distribution 0.56 +/- 0.30 times smaller than that of sucrose (P <
      0.001). The recovery of doxorubicin was less than that of liposomal doxorubicin
      (70 +/- 24% versus 94 +/- 17%, P < 0.05). The disposition of liposomal
      doxorubicin was found to be flow-limited, whereas a permeability-limited
      sequestration model fitted doxorubicin. The transfer of doxorubicin across the
      hepatocyte membrane was symmetrical (permeability - surface area product for
      influx 0.02 +/- 0.01 ml s/g versus 0.03 +/- 0.02 ml s/g for efflux) and
      consistent with diffusion. Electron microscopy confirmed that liposomes were
      restricted entirely to the sinusoidal lumen and none were seen in the
      extracellular space of Disse. Liposomal doxorubicin is restricted to the
      sinusoidal lumen, presumably secondary to steric exclusion by fenestrations in
      the sinusoidal endothelium. This provides the mechanism for the longer half-life
      and reduced hepatic extraction of liposomal doxorubicin compared with
      doxorubicin. The sinusoidal endothelium and fenestrations within the sinusoidal
      endothelium have an important role in hepatic pharmacology and are important
      considerations when designing liposomal preparations.

PMID- 15258104
TI  - Interaction of triazolam and ketoconazole in P-glycoprotein-deficient mice.
AB  - The role of P-glycoprotein (P-gp) on the distribution of the benzodiazepine
      triazolam (TRZ) and the azole antifungal agent ketoconazole (KET), and on the TRZ
      KET interaction, was studied using mdr1a(-) or mdr1a/b(-/-) mice (P-gp-deficient
      mice) and matched controls. TRZ and KET also were studied in Caco-2 cells in
      Transwell culture. After single i.p. injections of TRZ or KET in separate groups
      of control mice, brain concentrations of TRZ exceeded those in serum [brain/serum
      area under the concentration curve (AUC) ratio, 5.0], whereas brain/serum AUC
      ratios for KET were approximately 0.5. On the basis of single time points, brain
      concentrations of TRZ, or brain/serum ratios, were similar in P-gp-deficient
      animals compared with controls, whereas P-gp-deficient animals had significantly
      higher KET brain concentrations and brain/serum ratios. Coadministration of KET
      with TRZ increased TRZ concentrations in serum, liver, and brain, both in
      controls and in P-gp-deficient animals, probably attributable to impairment by
      KET of CYP3A-mediated clearance of TRZ. However, KET did not increase brain/serum
      ratios of TRZ in either group. In Caco-2 cells, basal-to-apical flux of TRZ was
      higher than apical-to-basal flux. However, verapamil (100 microM) did not alter
      flux in either direction. KET inhibited basal-to-apical transport of rho-damine
      123, with a 50% inhibitory concentration of 2.7 microM. Thus, TRZ does not appear
      to undergo measurable blood-brain barrier efflux transport by P-gp in this animal
      model. KET impairs clearance of TRZ but does not increase tissue uptake. However,
      KET itself may be a substrate for efflux transport at the blood-brain barrier.

PMID- 15258105
TI  - Inhibition of murine cytochrome P4501A by tacrine: in vitro studies.
AB  - Tacrine, a cholinesterase inhibitor, was approved for the treatment of
      Alzheimer's disease. Oxidative metabolism of tacrine occurs by CYP1A-catalyzed
      hydroxylation. In rats, it was observed that the area under the curve (AUC) of
      the second oral dose was consistently higher than the AUC after the first oral
      dose, which was not due to the accumulation of the drug in the plasma from the
      first dose. This finding suggested inhibition of the enzyme during metabolism or
      inhibition by a metabolite. The inhibitory mechanism was studied in liver and
      intestinal microsomes prepared from 3-methylcholanthrene-treated rats and with
      recombinant CYP1A1 and CYP1A2. Preincubation of CYP1A2 with tacrine and NADPH
      revealed a time-dependent inhibition of 7-ethoxyresorufin O-de-ethylation with a
      K(i) of 1.94 microM and a k(inact) of 0.091 min(-1). No time-dependent inhibition
      was observed with CYP1A1 or with 1-hydroxytacrine or 2-hydroxytacrine. Tacrine
      metabolism catalyzed by CYP1A was also carried out, and the partition ratio was
      estimated to be 22. A modified Michaelis-Menten equation involving mechanism
      based inhibition was derived and used to analyze the data. Reasonable parameter
      fits were obtained indicating that this equation is suitable to describe
      metabolism data when the substrate is a mechanism-based inhibitor of the enzyme.
      The probable inactivation mechanism involves either hydrogen atom abstraction to
      produce a carbon-centered radical intermediate at the benzylic position or
      insertion of OH(+) into a C-H bond with subsequent loss of water to produce a
      carbocation. Rapid rearrangement of the carbocation or radical and subsequent
      covalent binding of the tacrine moiety would result in enzyme inactivation.

PMID- 15258106
TI  - Human placental glucuronidation and transport of 3'azido-3'-deoxythymidine and
      uridine diphosphate glucuronic acid.
AB  - These studies were performed to characterize the contribution of the uridine
      diphosphate glucuronosyltransferase (UGT) enzymes to the clearance of 3'-azido-3'
      deoxythymidine (AZT) in vivo and to assess the regulation of UGT activity
      [including the disposition of the cofactor uridine diphosphate glucuronic acid
      (UDPGA)] in the placenta. Transport of AZT and the cofactor UDPGA across the
      human placenta and the glucuronidation capacity of the placenta for AZT were
      assessed using a human placental cell line (JEG-3), primary cultures of villous
      term placenta, placental subcellular fractions, and a recirculating perfusion
      model. Glucuronidation of AZT was consistently observed at approximately 2% of
      the dose administered. High levels of AZT in cultured primary placental cells and
      lines caused autoinhibition of AZT metabolism. AZT crossed the perfused placenta
      in a bidirectional fashion and was at equilibrium after 3 h, whereas the AZT
      glucuronide metabolite was excreted preferentially into the maternal compartment.
      In contrast, UDPGA (10 microM) was rapidly transferred from the maternal to the
      fetal circulation, being complete after 4 h of perfusion. AZT is transported and
      glucuronidated by the human placenta, but that placental metabolism of the drug
      is not significant for whole-body clearance. Likewise therapeutic failure of AZT
      (5-15%) is not due to placental obstruction of drug passage. Finally, the
      activity of the UGT enzymes in the placenta is not rate-limited by the supply of
      UDPGA cofactor, whereas the preferential transport of UDPGA toward the fetus
      observed here may indicate a role in fetal development.

PMID- 15258097
TI  - Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight
      infants.
AB  - Twenty percent of very-low-birth-weight (<1500 g) preterm infants experience a
      serious systemic infection, and despite advances in neonatal intensive care and
      antimicrobials, mortality is as much as threefold higher for these infants who
      develop sepsis than their counterparts without sepsis during their
      hospitalization. Outcomes may be improved by preventative strategies, earlier and
      accurate diagnosis, and adjunct therapies to combat infection and protect the
      vulnerable preterm infant during an infection. Earlier diagnosis on the basis of
      factors such as abnormal heart rate characteristics may offer the ability to
      initiate treatment prior to the onset of clinical symptoms. Molecular and
      adjunctive diagnostics may also aid in diagnosing invasive infection when
      clinical symptoms indicate infection but no organisms are isolated in culture.
      Due to the high morbidity and mortality, preventative and adjunctive therapies
      are needed. Prophylaxis has been effective in preventing early-onset group B
      streptococcal sepsis and late-onset Candida sepsis. Future research in
      prophylaxis using active and passive immunization strategies offers prevention
      without the risk of resistance to antimicrobials. Identification of the
      differences in neonatal intensive care units with low and high infection rates
      and implementation of infection control measures remain paramount in each
      neonatal intensive care unit caring for preterm infants.

PMID- 15258107
TI  - Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole,
      esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome
      P450 activities.
AB  - The human clearance of proton pump inhibitors (PPIs) of the substituted
      benzimidazole class is conducted primarily by the hepatic cytochrome P450 (P450)
      system. To compare the potency and specificity of the currently used PPIs (i.e.,
      omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) as
      inhibitors of four cytochrome P450 enzymes (CYP2C9, 2C19, 2D6, and 3A4), we
      performed in vitro studies using human liver microsomal preparations and
      recombinant CYP2C19. Sample analysis was done using selected reaction monitoring
      liquid chromatography/tandem mass spectometry. With several systems for CYP2C19
      activity (two marker reactions, S-mephenytoin 4'-hydroxylation and R-omeprazole 5
      hydroxylation, tested in either human liver microsomes or recombinant CYP2C19),
      the five PPIs showed competitive inhibition of CYP2C19 activity with K(i) of 0.4
      to 1.5 microM for lansoprazole, 2 to 6 microM for omeprazole, approximately 8
      microM for esomeprazole, 14 to 69 microM for pantoprazole, and 17 to 21 microM
      for rabeprazole. Pantoprazole was a competitive inhibitor of both CYP2C9
      catalyzed diclofenac 4'-hydroxylation and CYP3A4-catalyzed midazolam 1'
      hydroxylation (K(i) of 6 and 22 microM, respectively), which were at least 2
      times more potent than the other PPIs. All PPIs were poor inhibitors of CYP2D6
      mediated bufuralol 1'-hydroxylation with IC(50) > 200 microM. The inhibitory
      potency of a nonenzymatically formed product of rabeprazole, rabeprazole
      thioether, was also investigated and showed potent, competitive inhibition with
      K(i) values of 6 microM for CYP2C9, 2 to 8 microM for CYP2C19, 12 microM for
      CYP2D6, and 15 microM for CYP3A4. The inhibitory potency of R-omeprazole on the
      four studied P450 enzymes was also studied and showed higher inhibitory potency
      than its S-isomer on CYP2C9 and 2C19 activities. Our data suggest that, although
      the inhibitory profiles of the five studied PPIs were similar, lansoprazole and
      pantoprazole are the most potent in vitro inhibitors of CYP2C19 and CYP2C9,
      respectively. Esomeprazole showed less inhibitory potency compared with
      omeprazole and its R-enantiomer. The inhibitory potency of rabeprazole was
      relatively lower than the other PPIs, but its thioether analog showed potent
      inhibition on the P450 enzymes investigated, which may be clinically significant.

PMID- 15258108
TI  - Inhibitory effects of pomelo on the metabolism of tacrolimus and the activities
      of CYP3A4 and P-glycoprotein.
AB  - We recently reported a case of increase in the blood level of tacrolimus
      following intake of pomelo in a renal transplant recipient. To clarify the
      mechanism of this increase in the blood level of tacrolimus, we investigated the
      effect of pomelo juice extract on the activities of CYP3A4 and P-glycoprotein, in
      comparison with that of extract of grapefruit juice (GFJ). The 10% ethyl acetate
      extracts of the juice of three pomelos of different origins (Banpeiyu, pomelo I;
      Hirado Buntan, pomelo II; and Tosa Buntan, pomelo III) and GFJ significantly
      inhibited 6beta-hydroxylation of testosterone in human liver microsomes by 76.4,
      67.2, 37.5, and 83.9%, respectively. The extract of pomelo I was as potent as
      that of GFJ. The metabolism of tacrolimus itself was also inhibited by the
      extract of pomelo I, as well as that of GFJ. Furthermore, the inhibition of both
      6beta-hydroxylation of testosterone and metabolism of tacrolimus by pomelo I and
      GFJ was preincubation time-dependent. On the other hand, the extract of pomelo I
      had little effect on the transcellular transport of tacrolimus or [(3)H]digoxin
      across a monolayer of LLC-GA5-COL150 cells (a porcine kidney epithelial cell
      line, LLC-PK1, transfected with human MDR1 cDNA and overexpressing human P
      glycoprotein). In conclusion, pomelo constituents inhibit the activity of CYP3A4
      and may thereby produce an increase in the blood level of tacrolimus.

PMID- 15258109
TI  - Effect of dexamethasone treatment on the expression and function of transport
      proteins in sandwich-cultured rat hepatocytes.
AB  - Dexamethasone (DEX) is a well established inducer of CYP3A. These studies
      examined the influence of DEX treatment on transport protein expression and
      function in sandwich-cultured (SC) rat hepatocytes. Freshly isolated hepatocytes
      were cultured between two layers of gelled collagen and maintained in Dulbecco's
      modified Eagle's medium supplemented with DEX (0.1 microM, 0-48 h and 0.1-100
      microM, 48-96 h). The expression of sinusoidal [(organic anion transporting
      polypeptide 1a1 (Oatp1a1), Oatp1a4, multidrug resistance-associated protein 3
      (Mrp3), and Na(+)-dependent taurocholate cotransporting polypeptide (Ntcp)] and
      canalicular [bile salt export pump (Bsep), multidrug resistance protein 1a/b
      (Mdr1a/b), and Mrp2] transport proteins was determined by Western blot analysis.
      The accumulation and biliary excretion index (BEI; percentage of accumulated
      substrate in canalicular networks) of the probe substrates taurocholate (TC; 1
      microM, 10 min), rhodamine 123 (Rh123; 10 microM, 30 min), and carboxy-2',7'
      dichlorofluorescein (CDF; 10 microM, 10 min) were employed as measures of
      canalicular transport protein function in SC rat hepatocytes. DEX treatment
      increased CYP3A1/2, Oatp1a4, and Mrp2 expression, decreased the expression of
      Ntcp, and did not seem to alter the expression of Oatp1a1, Mrp3, Mdr1a/b, or
      Bsep. The BEI of CDF, an Mrp2 substrate, increased from 18 to 37% after DEX
      treatment (100 microM). The accumulation of TC, an Ntcp substrate, was reduced
      (<50% of control), whereas the BEI of TC, also a Bsep substrate, was unchanged.
      Treatment of SC rat hepatocytes with DEX resulted in alterations in the
      expression of CYP3A1/2 and some hepatic transport proteins. Modest alterations in
      hepatic transport protein function were consistent with changes in protein
      expression.

PMID- 15258110
TI  - Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450
      1b1.
AB  - The cytochrome P450 family 1 (CYP1) is considered to be one of the xenobiotic
      metabolizing enzyme families and is responsible for oxidative metabolism of
      polycyclic aromatic hydrocarbons. For example, mouse Cyp1b1 was originally
      identified as the enzyme responsible for oxidative metabolism of 7,12
      dimethylbenz(alpha)anthracene (DMBA). A comparison of the kinetics of this
      metabolism by mouse and human CYP1B1 orthologs revealed the mouse enzyme to have
      a more favorable metabolism of DMBA, with a catalytic efficiency ratio (CER) of
      0.23. However, CYP1 enzymes are also capable of metabolism of endobiotics, and in
      the present study, the metabolism of retinoids and lipid endobiotics by human
      CYP1B1 and mouse Cyp1b1 orthologs was compared. Both hemoproteins oxidized
      retinol to retinal and retinal to retinoate, but did not oxidize retinoate. The
      CYP1B1 to Cyp1b1 CERs were 13 and 26 for the two steps, respectively; the Cyp1b1
      K(m(app)) values for retinoids were 20-fold higher. Human family 1 cytochromes
      P450 had unique regional specificities for arachidonate oxidation: the major
      metabolites of CYP1A1, CYP1A2, and CYP1B1 were 75% terminal
      hydroxyeicosatetraenoic fatty acids (HETEs), 52% epoxyeicosatrienoic fatty acids
      (EETs), and 54% mid-chain HETEs, respectively. CYP1A1 and CYP1B1 K(m(app)) values
      for arachidonate were about 30 microM, whereas CYP1A2 K(m(app)) was 95 microM.
      The major metabolites of arachidonic acid by Cyp1b1 were EETs (50%) and midchain
      HETEs (37%). The mouse ortholog had a CER for metabolite production of 64 due to
      a K(m(app)) of 0.5 mM for arachidonate.

PMID- 15258111
TI  - In vitro and in vivo metabolism of a potent and selective integrin alpha v beta 3
      antagonist in rats, dogs, and monkeys.
AB  - Compound A (3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyrindin-2-yl)propyl]
      imidazolidin-1-yl]-3(S)-(6-methoxy-pyridin-3-yl)-propionic acid), a potent and
      selective antagonist of integrin alpha(v)beta(3) receptor, is under development
      for treatment of osteoporosis. This study describes metabolism and excretion of A
      in vivo in rats, dogs, and monkeys, and metabolism of A in vitro in primary
      hepatocytes from rats, dogs, monkeys, and humans. In all three animal species
      studied, A was primarily excreted as unchanged drug and, to a lesser degree, as
      phase I and phase II metabolites. Major biotransformation pathways of A included
      glucuronidation/glucosylation on the carboxylic group to form acyl-linked
      glucuronides/glucosides; and oxidation on the tetrahydronaphthyridine moiety to
      generate a carbinolamine and its further metabolized products. Minor pathways
      involved O-demethylation and hydroxylations on the alkyl chain. Only in rats, a
      glutathione adduct of A was also observed, and its formation is proposed to be
      via an iminium intermediate on the tetrahydronaphthyridine ring. Similar
      metabolic pathways were observed in the incubates of hepatocytes from the
      corresponding animals as well as from humans. CYP 3A and 2D subfamilies were
      capable of metabolizing A to its oxidative products. Overall, these in vitro and
      in vivo findings should provide useful insight on possible biotransformation
      pathways of A in humans.

PMID- 15258112
TI  - Evaluation of 5-hydroxytryptophol and other endogenous serotonin (5
      hydroxytryptamine) analogs as substrates for UDP-glucuronosyltransferase 1A6.
AB  - Serotonin is a specific in vitro substrate for human UDP-glucuronosyltransferase
      (UGT) 1A6. In this study, the contribution of UGT1A6 to the glucuronidation of
      endogenous structural analogs of serotonin, including 5-hydroxytryptophol, N
      acetylserotonin, and 6-hydroxymelatonin, was evaluated using available
      recombinant human UGT isoforms, human liver microsomes, and liver microsomes from
      animals that do not express functional UGT1A6 (Gunn rats and cats). Only UGT1A6
      and UGT1A9 were found to glucuronidate 5-hydroxytryptophol at a concentration of
      2 mM, although the glucuronidation rate with UGT1A6 was over 10 times that of
      UGT1A9. K(m) values for human liver microsomes (156, 141, and 134 microM) were
      most similar to that of expressed UGT1A6 (135 microM) but vastly different from
      that of UGT1A9 (3674 microM). 5-Hydroxytryptophol glucuronidation by human liver
      microsomes (n = 54) correlated well with serotonin glucuronidation (R(s) = 0.83)
      and UGT1A6 protein content (R(s) = 0.85). 5-Hydroxytryptophol also competitively
      inhibited serotonin glucuronidation by human liver microsomes (K(i) = 291 microM)
      and UGT1A6 (K(i) = 200 microM). N-acetylserotonin was glucuronidated most
      extensively by UGT1A6, although UGT1A9 and UGT1A10 showed moderate catalysis. 6
      Hydroxymelatonin was glucuronidated largely by UGT1A9 and UGT1A10 but not at all
      by UGT1A6. Gunn rat liver glucuronidation rates for serotonin, 5
      hydroxytryptophol, N-acetylserotonin, and 6-hydroxymelatonin were 11, 5, 32, and
      3%, respectively, of that of normal rat liver. Cat liver microsomes did not
      glucuronidate serotonin, whereas relatively low activities were observed for the
      other indole substrates. In conclusion, these results indicate that human UGT1A6
      plays a predominant role in the glucuronidation of 5-hydroxytryptophol and N
      acetylserotonin, whereas 6-hydroxymelatonin is not a substrate for this enzyme.

PMID- 15258113
TI  - Sequential metabolism of 2,3,7-trichlorodibenzo-p-dioxin (2,3,7-triCDD) by
      cytochrome P450 and UDP-glucuronosyltransferase in human liver microsomes.
AB  - Metabolism of polychlorinated dibenzo-p-dioxins by cytochrome P450 (P450) and UDP
      glucuronosyltransferase (UGT) was examined using a recombinant enzyme system and
      human liver microsomes. We analyzed the glucuronidation of 2,3,7-trichlorodibenzo
      p-dioxin (2,3,7-triCDD) by rat CYP1A1 expressed in yeast microsomes and human UGT
      expressed in baculovirus-infected insect cells. Multiple UGT isozymes showed
      glucuronidation activity toward 8-hydroxy-2,3,7-triCDD (8-OH-2,3,7-triCDD), which
      was produced by CYP1A1. Of these UGTs, UGT1A1, 1A9, and 2B7, which are
      constitutively expressed in human livers, showed remarkable activity toward 8-OH
      2,3,7-triCDD. The apparent kinetic parameters of glucuronidation, K(m) and
      k(cat), were estimated to be 0.8 microM and 1.8 min(-1), respectively, for
      UGT1A1, 0.8 microM and 1.8 min(-1), respectively, for UGT1A9, and 3.9 microM and
      7.0 min(-1), respectively, for UGT2B7. In human liver microsomes with NADPH and
      UDP-glucuronic acid, 2,3,7-triCDD was first converted to 8-OH-2,3,7-triCDD, then
      further converted to its glucuronide. We compared the ability of 10 human liver
      microsomes to metabolize 2,3,7-triCDD and observed a significant difference in
      the glucuronidation of 2,3,7-triCDD that originated from the difference of the
      P450-dependent hydroxylation of 2,3,7-triCDD.

PMID- 15258114
TI  - NADPH-dependent formation of polar and nonpolar estrogen metabolites following
      incubations of 17 beta-estradiol with human liver microsomes.
AB  - By using a versatile high-pressure liquid chromatography method (total elution
      time approximately 135 min) developed in the present study, we detected the
      formation of some 20 nonpolar radioactive metabolite peaks (designated as M1
      through M20), in addition to a large number of polar hydroxylated or keto
      metabolites, following incubations of [(3)H]17beta-estradiol with human liver
      microsomes or cytochrome P450 3A4 in the presence of NADPH as a cofactor. The
      formation of most of the nonpolar estrogen metabolite peaks (except M9) was
      dependent on the presence of human liver microsomal proteins, and could be
      selectively inhibited by the presence of carbon monoxide. Among the four
      cofactors (NAD, NADH, NADP, NADPH) tested, NADPH was the optimum cofactor for the
      metabolic formation of polar and nonpolar estrogen metabolites in vitro, although
      NADH also had a weak ability to support the reactions. These observations suggest
      that the formation of most of the nonpolar estrogen metabolite peaks requires the
      presence of liver microsomal enzymes and NADPH. Chromatographic analyses showed
      that these nonpolar estrogen metabolites were not the monomethyl ethers of
      catechol estrogens or the fatty acid esters of 17beta-estradiol. Analyses using
      liquid chromatography/mass spectrometry and NMR showed that M15 and M16, two
      representative major nonpolar estrogen metabolites, are diaryl ether dimers of
      17beta-estradiol. The data of our present study suggest a new metabolic pathway
      for the NADPH-dependent, microsomal enzyme-mediated formation of estrogen diaryl
      ether dimers, along with other nonpolar estrogen metabolites.

PMID- 15258115
TI  - Modeling the in vitro intrinsic clearance of the slowly metabolized compound
      tolbutamide determined in sandwich-cultured rat hepatocytes.
AB  - An alternative approach is introduced in determining the in vitro intrinsic
      clearance of slowly metabolized compounds. The longterm sandwich rat hepatocyte
      culture was exploited, allowing for sufficient substrate depletion to obtain a
      reliable clearance estimation; in its physiology, it resembles the in vivo liver,
      thus allowing in vivo extrapolation of the in vitro clearance value. Substrate
      depletion of tolbutamide and the formation of its metabolites hydroxytolbutamide
      and carboxytolbutamide were measured in the medium and sandwich layer. Depletion
      data from the medium were fitted to a mathematical model incorporating system
      dependent parameters (diffusion, protein binding, and partitioning) to calculate
      the hepatocytes' intrinsic clearance. Based on the decrease of the parent
      compound in the medium, a specific intrinsic clearance value, i.e., clearance per
      unit of volume of hepatocytes, of 0.085 min(-1) was fitted. This value was in
      accordance with in vivo and in vitro values from the literature. The model was
      verified with substrate depletion data from the sandwich layer. Data on
      metabolite formation showed an incomplete mass balance. A radiochemical
      experiment revealed the presence of three additional metabolites. These
      metabolites were analyzed by liquid chromatography-mass spectometry. One was
      identified as p-tolysulfonylurea. The structure of the other two needs to be
      elucidated. After the addition of these compounds to the metabolic pattern, the
      mass balance was completed. The in vitro clearance value was incorporated in a
      physiologically based pharmacokinetic literature model of tolbutamide that
      accurately describes the plasma concentration. The approach used in this study
      successfully predicts the intrinsic clearance of tolbutamide. In addition, the
      sandwich rat hepatocyte culture also proves to be useful in the identification of
      metabolic pathways.

PMID- 15258116
TI  - Peripheral chemoreceptor control of ventilation following sustained hypoxia in
      young and older adult humans.
AB  - The rate and duration of peripheral chemoreceptor resensitization following
      sustained hypoxia was characterized in young and older (74-year-old) adults. In
      addition, cerebral blood velocity (CBV) was measured in young subjects during and
      following the relief from sustained hypoxia. Following 20 min of sustained
      eucapnic hypoxia (50 mmHg), subjects were re-exposed to brief (1.5 min) hypoxic
      pulses (50 mmHg), and the magnitude of the ventilatory response was used to gauge
      peripheral chemosensitivity. Five minutes after the relief from sustained
      hypoxia, ventilation (V(E)) increased to 40.3 +/- 4.5% of the initial hypoxic
      ventilatory response, and by 36 min V(E) increased to 100%, indicating that
      peripheral chemosensitivity to hypoxia was restored. The V(E) response magnitude
      plotted versus time demonstrated that V(E), hence peripheral chemosensitivity,
      was restored at a rate of 1.9% per minute. Cerebral blood flow (CBF, inferred
      from CBV) remained constant during sustained hypoxia and increased by the same
      magnitude during the hypoxic pulses, suggesting that CBF has a small, if any,
      impact on the decline in V(E) during hypoxia and its subsequent recovery. To
      address the issue of whether hypoxic pulses affect subsequent challenges, series
      (continuous hypoxic pulses at various recovery intervals) and parallel (only 1
      pulse per trial) methods were used. There were no differences in the ventilatory
      responses between the series and parallel methods. Older adults demonstrated a
      similar rate of recovery as in the young, suggesting that ageing in active older
      adults does not affect the peripheral chemoreceptor response.

PMID- 15258117
TI  - L-thyroxine increases susceptibility of adult rats to low K+-induced ventricular
      fibrillation, and sinus rhythm restoration in old rats.
AB  - Hypokalaemia increases the risk for life-threatening arrhythmias; however, data
      about interaction with thyroid status are lacking. The aim of this study was to
      investigate vulnerability of l-thyroxine (T(4))-treated adult and old rats to low
      K(+)-induced ventricular fibrillation (VF) as well as the ability of the heart to
      recover sinus rhythm. The experiments were performed on isolated heart
      preparations using the heart of 4- and 20-month-old female Wistar rats without
      and with feeding with T(4) 50 microg (100 g day)(-1) over a period of 2 weeks.
      Perfusion of the isolated heart with oxygenated Krebs-Henseleit solution at
      constant pressure was followed by perfusion with K(+)-deficient solution until
      occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused
      with normal solution for 10 min, during which sinus rhythm was restored. ECG,
      left ventricular pressure (LVP) and coronary flow were continuously monitored.
      The results showed that compared with untreated rats, the onset of low K(+)
      induced ventricular premature beats was delayed and their number was
      significantly decreased in both T(4)-treated groups. Nevertheless, VF occurred
      earlier in T(4)-treated than in non-treated adult rats (6.78 +/- 0.28 vs. 9.59 +/
      0.55 min, P < 0.05), whereas the difference was not significant in aged animals.
      Furthermore, sinus rhythm appeared earlier in old T(4)-treated rats compared with
      non-treated rats (7.18 +/- 0.57 vs. 8.94 +/- 0.64 min, P < 0.05), whereas in
      adult hearts it set in at practically the same time regardless of treatment. In
      conclusion, our results indicate that administration of a pharmacological dose of
      T(4) can increase the risk of low K(+)-induced VF in adult but not in old
      animals; in the latter it even facilitated restoration of sinus rhythm. Moreover,
      enhanced mechanical function was observed in both adult and old T(4)-treated
      hearts.

PMID- 15258118
TI  - Strain softening behaviour in nonviable rat right-ventricular trabeculae, in the
      presence and the absence of butanedione monoxime.
AB  - Strain softening is commonly reported during mechanical testing of passive whole
      hearts. It is typically manifested as a stiffer force-extension relationship in
      the first deformation cycle relative to subsequent cycles and is distinguished
      from viscoelasticity by a lack of recovery of stiffness, even after several hours
      of rest. The cause of this behaviour is presently unknown. In order to
      investigate its origins, we have subjected trabeculae to physiologically
      realistic extensions (5-15% of muscle length at 26 degrees C and 0.5 mm Ca(2+)),
      while measuring passive force and dynamic stiffness. While we did not observe
      strain softening in viable trabeculae, we found that it was readily apparent in
      nonviable (electrically inexcitable) trabeculae undergoing the same extensions.
      This result was obtained in both the presence and absence of 2,3-butanedione
      monoxime (BDM). Furthermore, BDM had no effect on the passive compliance of
      viable specimens, while its presence partly inhibited, but could not prevent,
      stiffening of nonviable specimens. Loss of viability was accompanied by a uniform
      increase of dynamic stiffness over all frequencies examined (0.2-100 Hz). The
      presence of strain softening during length extensions of nonviable tissue
      resulted in a comparable uniform decrease of dynamic stiffness. It is therefore
      concluded that strain softening is neither intrinsic to viable rat right
      ventricular trabeculae nor influenced by BDM but, rather, reflects irreversible
      damage of tissue in partial, or full, rigor.

PMID- 15258119
TI  - Long-term structural and functional consequences of cardiac ischaemia-reperfusion
      injury in vivo in mice.
AB  - The short-term (<24 h) consequences of oxidative stress induced by ischaemia
      reperfusion (IR) have been studied extensively in the mouse heart. However, much
      less is known about the long-term effects inflicted by a brief ischaemic period
      on the murine heart. We therefore examined the structural and functional
      consequences of a 30 min ischaemic period after 2 and 8 weeks of reperfusion and
      compared these to the effects induced by permanent occlusion of the left anterior
      descending coronary artery (LAD). The latter procedure resulted in transmural
      myocardial infarcts of about 52% of the left ventricle. In contrast, the single
      30 min ischaemic period led to infarct sizes of about 13% of the left ventricle
      (range, 4-23%) at 2 and 8 weeks after reperfusion. Maximal cardiac contractility
      responses (+dP/dt) to dobutamine infusion and volume loading were depressed at 2,
      but not at 8 weeks after IR. The restoration of cardiac contractility at 8 weeks
      after IR was associated with a significant 20% enlargement of the end-diastolic
      volume and 16% increase of the left ventricular wall thickness. These changes in
      cardiac geometry were less pronounced at 2 weeks after IR. Histological
      examination revealed that the IR injury was associated with prominent
      calcification. At 2 and at 8 weeks after IR, 25 +/- 5 and 38 +/- 5% of the
      injured area was calcified as observed in 69 and 73% of the animals,
      respectively. After permanent occlusion of the LAD, calcification was not
      observed and healing of the affected area was characterized by thinning and
      dilatation of the infarcted myocardium. These data indicate that, in mice, a
      single 30 min period of ischaemia reduced ventricular contractility up to at
      least 2 weeks after reperfusion. However, 8 weeks after IR, cardiac function was
      restored by eccentric hypertrophy associated with calcification of the injured
      ventricular wall.

PMID- 15258120
TI  - Reliability of isolated isometric function measures in rat muscles composed of
      different fibre types.
AB  - The present study investigated the absolute reliability (R(Ab)) of isometric
      measures of time-to-peak tension (TTP), half-rise time ((1/2)RT), half-fall time
      ((1/2)FT), twitch force (TW(f)) tetanic force (TET(f)) and the sag ratio as
      applied to the slow soleus (SOL) and the fast-twitch extensor digitorum longus
      (EDL) and medial gastrocnemius (MG) muscles of the rat hindlimb. In addition, the
      relationship of each individual isometric measure was examined with regard to the
      pattern of myosin heavy chain (MHC) isoform expression. Measures of TTP, (1/2)RT,
      (1/2)FT and sag ratio were negatively correlated with MHCIId(x) and MHCIIb (P <
      0.0001), and positively correlated with MHCI (P < 0.0001). TW(f) and TET(f) were
      negatively correlated with MHCI content (P < 0.0001) and positively with
      MHCIId(x) (P < 0.0001) and MHCIIb (P < 0.001). Comparisons of isometric measures
      using a paired Student's t test revealed that they were not different between the
      right and left legs; all measures displayed high correlations between the left
      and right legs (r= 0.71-0.85, P < 0.0001). In contrast to standard tests of
      statistical significance, these functional measures exhibited a considerable
      range of R(Ab) when individual muscles were studied in only one hindlimb. When
      averaged across all muscles, however, the (1/2)FT, (1/2)RT, TW(f) and TTP
      measures possessed high overall reliability; measures of TET(f) and sag ratio
      were moderately reliable. The results of this study show that the isometric
      measures studied possess significant predictive value with regard to MHC isoform
      content; the left and right legs are interchangeable but display a considerable
      range of reliability when only one hindlimb is studied.

PMID- 15258121
TI  - Spontaneous changes in guinea-pig respiratory pattern during barometric
      plethysmography: role of catecholamines and nitric oxide.
AB  - Barometric plethysmography for unrestrained animals is a non-invasive method that
      allows repetitive measurements of pulmonary function, but habituation of the
      conscious animal to this technique has not been explored. Respiratory frequency
      (f(R)) and 'enhanced pause' (P(enh)) were measured by barometric plethysmography
      for a period of 8 h in guinea-pigs. Compared with basal values, during the first
      hour of recording a progressive increase in P(enh) (up to 25-50%) and a
      corresponding decrease in f(R) were recorded, followed by a relative plateau in
      each for up to 8 h. These changes were avoided by a 30-min pretreatment with
      propranolol and l-NAME (nitric oxide synthase inhibitor), with P(enh) values as
      high as this plateau phase since the beginning of recording. Atropine, salbutamol
      or budesonide did not modify the progressive increment in P(enh). We concluded
      that catecholamines and nitric oxide are released when guinea-pigs are introduced
      into the plethysmographic chamber, leading to initial low P(enh) values. These
      mediators probably diminish owing to habituation of the animal to the new
      environment, with an apparent progressive increment in P(enh). These spontaneous
      changes in P(enh) and f(R) must be taken into account during barometric
      plethysmography in order to avoid misinterpretation of the results.

PMID- 15258122
TI  - Resistance to fatigue of individual Xenopus single skeletal muscle fibres is
      correlated with mitochondrial volume density.
AB  - The purpose of the present study was to compare the individual fatigue
      characteristics of isolated single skeletal muscle fibres with their
      mitochondrial volume density (MVD), using direct histological morphometry. Single
      muscle fibres (n= 14) were microdissected from lumbrical muscle of adult female
      Xenopus laevis, and force was measured while fibres were stimulated (tetanic
      contractions of 200 ms trains with 70 Hz stimuli at 9 V) at progressively
      increasing frequencies (2 min each at 0.25, 0.33, 0.5 and 1 contractions s(-1))
      until fatigue (<50% initial maximal force) had been established. Following the
      end of the fatigue protocol, MVD was determined by electron microscopy. Time to
      fatigue varied among the individual fibres from 3.3 to 10 min. MVD of individual
      fibres ranged from 3.0 to 9.2% and was positively correlated (r= 0.93) with time
      to fatigue of corresponding fibres. These results, using direct histological
      measurements of MVD: (1) support on a single cell basis the notion that oxidative
      capacity is a major determinant of muscle fatigue resistance; and (2) show that
      the fatigue profile of a single cell can be used to predict oxidative capacity.

PMID- 15258123
TI  - Functional organization of respiratory neurones: a brief review of current
      questions and speculations.
AB  - This article presents a short overview of current knowledge about the medullary
      respiratory neurones and the generation of breathing rhythm. The background
      respiratory neurophysiology of the medulla and pons is briefly reviewed, with
      some current ideas about the organization of the pontine-medullary respiratory
      control system and its development. Questions and speculations about the
      organization and generation of respiratory rhythm are included, with a view to
      stimulating experiments to provide answers.

PMID- 15258124
TI  - Muscle mechanical advantage of human walking and running: implications for energy
      cost.
AB  - Muscular forces generated during locomotion depend on an animal's speed, gait,
      and size and underlie the energy demand to power locomotion. Changes in limb
      posture affect muscle forces by altering the mechanical advantage of the ground
      reaction force (R) and therefore the effective mechanical advantage (EMA = r/R,
      where r is the muscle mechanical advantage) for muscle force production. We used
      inverse dynamics based on force plate and kinematic recordings of humans as they
      walked and ran at steady speeds to examine how changes in muscle EMA affect
      muscle force-generating requirements at these gaits. We found a 68% decrease in
      knee extensor EMA when humans changed gait from a walk to a run compared with an
      18% increase in hip extensor EMA and a 23% increase in ankle extensor EMA.
      Whereas the knee joint was extended (154-176 degrees) during much of the support
      phase of walking, its flexed position (134-164 degrees) during running resulted
      in a 5.2-fold increase in quadriceps impulse (time-integrated force during
      stance) needed to support body weight on the ground. This increase was associated
      with a 4.9-fold increase in the ground reaction force moment about the knee. In
      contrast, extensor impulse decreased 37% (P < 0.05) at the hip and did not change
      at the ankle when subjects switched from a walk to a run. We conclude that the
      decrease in limb mechanical advantage (mean limb extensor EMA) and increase in
      knee extensor impulse during running likely contribute to the higher metabolic
      cost of transport in running than in walking. The low mechanical advantage in
      running humans may also explain previous observations of a greater metabolic cost
      of transport for running humans compared with trotting and galloping quadrupeds
      of similar size.

PMID- 15258125
TI  - Intratracheal adenoviral-mediated delivery of iNOS decreases pulmonary
      vasoconstrictor responses in rats.
AB  - We hypothesized that adenovirus-mediated inducible nitric oxide synthase (iNOS)
      gene transduction of the lung would result in time-dependent iNOS overexpression
      and attenuate the vascular constrictor responses to a thromboxane mimetic, U
      46619. Rats were treated via the trachea with surfactant alone (sham), surfactant
      containing an adenoviral construct with a cytomegalovirus promoter-regulated
      human iNOS gene (Adeno-iNOS), or an adenoviral construct without a gene insert
      (Adeno-Control). Adeno-iNOS-transduced rats demonstrated human iNOS mRNA and
      increased iNOS protein levels only in the lungs. Immunohistochemistry of lungs
      from Adeno-iNOS-treated animals demonstrated transgene expression in alveolar
      wall cells. In the lungs from Adeno-iNOS-transduced rats, the expression of iNOS
      protein and exhaled nitric oxide concentrations were increased on days 1-4 and 7
      but returned to baseline values by day 14. The administration of the selective
      iNOS inhibitor L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) decreased
      exhaled nitric oxide concentrations to levels found in Adeno-Control-transduced
      lungs. In a second group of rats, the segmental vasoconstrictor responses to U
      46619 were determined in isolated, perfused lungs 3 days after transduction.
      Lungs from rats transduced with Adeno-iNOS had reduced total, arterial, and
      venous vasoconstrictor responses to U-46619 compared with sham, Adeno-Control,
      and control groups. In a third set of experiments, the response to 400 nM U-46619
      in the presence of 10 microM L-NIL was not different in the isolated lungs from
      Adeno-Control- and Adeno-iNOS-transduced rats. We conclude that adenovirus
      mediated iNOS gene transduction of the lung results in time-dependent iNOS
      overexpression, which attenuates the vascular constrictor responses to the
      thromboxane mimetic U-46619.

PMID- 15258126
TI  - fMRI signal changes in response to forced expiratory loading in congenital
      central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) patients show impaired
      ventilatory responses to CO2 and hypoxia and reduced drive to breathe during
      sleep but retain appropriate breathing patterns in response to volition or
      increased exercise. Breath-by-breath influences on heart rate are also deficient.
      Using functional magnetic resonance imaging techniques, we examined responses
      over the brain to voluntary forced expiratory loading, a task that CCHS patients
      can perform but that results in impaired rapid heart rate variation patterns
      normally associated with the loading challenge. Increased signals emerged in
      control (n = 14) over CCHS (n = 13; ventilator dependent during sleep but not
      waking) subjects in the cingulate and right parietal cortex, cerebellar cortex
      and fastigial nucleus, and basal ganglia, whereas anterior cerebellar cortical
      sites and deep nuclei, dorsal midbrain, and dorsal pons showed increased signals
      in the patient group. The dorsal and ventral medulla showed delayed responses in
      CCHS patients. Primary motor and sensory areas bordering the central sulcus
      showed comparable responses in both groups. The delayed responses in medullary
      sensory and output regions and the aberrant reactions in cerebellar and pontine
      sensorimotor coordination areas suggest that rapid cardiorespiratory integration
      deficits in CCHS may stem from defects in these sites. Additional autonomic and
      perceptual motor deficits may derive from cingulate and parietal cortex
      aberrations.

PMID- 15258127
TI  - Assessment of low-frequency fatigue with two methods of electrical stimulation.
AB  - The aim of this study was to compare the use of transcutaneous vs. motor nerve
      stimulation in the evaluation of low-frequency fatigue. Nine female and eleven
      male subjects, all physically active, performed a 30-min downhill run on a
      motorized treadmill. Knee extensor muscle contractile characteristics were
      measured before, immediately after (Post), and 30 min after the fatiguing
      exercise (Post30) by using single twitches and 0.5-s tetani at 20 Hz (P20) and 80
      Hz (P80). The P20-to-P80 ratio was calculated. Electrical stimulations were
      randomly applied either maximally to the femoral nerve or via large surface
      electrodes (ES) at an intensity sufficient to evoke 50% of maximal voluntary
      contraction (MVC) during a 80-Hz tetanus. Voluntary activation level was also
      determined during isometric MVC by the twitch-interpolation technique. Knee
      extensor MVC and voluntary activation level decreased at all points in time
      postexercise (P < 0.001). P20 and P80 displayed significant time x gender x
      stimulation method interactions (P < 0.05 and P < 0.001, respectively). Both
      stimulation methods detected significant torque reductions at Post and Post30.
      Overall, ES tended to detect a greater impairment at Post in male and a lesser
      one in female subjects at both Post and Post30. Interestingly, the P20-P80 ratio
      relative decrease did not differ between the two methods of stimulation. The low
      to-high frequency ratio only demonstrated a significant time effect (P < 0.001).
      It can be concluded that low-frequency fatigue due to eccentric exercise appears
      to be accurately assessable by ES.

PMID- 15258128
TI  - Adaptations to free-fall impact are different in the shafts and bone ends of rat
      forelimbs.
AB  - Impact exercise can have beneficial effects on the growing skeleton. To
      understand what changes it promotes in the shafts and ends of weight-bearing
      bones, we measured the effects of impact from repetitive free falls in growing
      rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups
      (n = 10 each). Controls were not dropped, whereas those subjected to impact were
      dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per
      day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area
      (CSA), cross-sectional moments of inertia, and volumetric bone mineral density
      (BMD) were measured by peripheral quantitative computed tomography. In the shafts
      of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater
      ultimate breaking force, minimum and maximum second moments of area, and CSA but
      not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD
      increased but CSA did not. Landing from 30 and 60 cm produced peak impact forces
      of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5
      and 7.7 times the standing hind foot weight for each hind foot. Overall, free
      fall impact affected the forelimbs by increasing trabecular bone density in the
      bone ends and improving the strength at the shaft as a result of geometric
      improvements. These results indicate that adaptation to impact may occur by
      different mechanisms in bone end and shaft regions.

PMID- 15258129
TI  - Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in
      neonatal rat pups.
AB  - Carotid bodies are functionally immature at birth and exhibit poor sensitivity to
      hypoxia. Previous studies have shown that continuous hypoxia at birth impairs
      hypoxic sensing at the carotid body. Intermittent hypoxia (IH) is more frequently
      experienced in neonatal life. Previous studies on adult animals have shown that
      IH facilitates hypoxic sensing at the carotid bodies. On the basis of these
      studies, in the present study we tested the hypothesis that neonatal IH
      facilitates hypoxic sensing of the carotid body and augments ventilatory response
      to hypoxia. Experiments were performed on 2-day-old rat pups that were exposed to
      16 h of IH soon after the birth. The IH paradigm consisted of 15 s of 5% O2
      (nadir) followed by 5 min of 21% O2 (9 episodes/h). In one group of experiments
      (IH and control, n = 6 pups each), sensory activity was recorded from ex vivo
      carotid bodies, and in the other (IH and control, n = 7 pups each) ventilation
      was monitored in unanesthetized pups by plethysmography. In control pups, sensory
      response of the carotid body was weak and was slow in onset (approximately 100
      s). In contrast, carotid body sensory response to hypoxia was greater and the
      time course of the response was faster (approximately 30 s) in IH compared with
      control pups. The magnitude of the hypoxic ventilatory response was greater in IH
      compared with control pups, whereas changes in O2 consumption and CO2 production
      during hypoxia were comparable between both groups. The magnitude of ventilatory
      stimulation by hyperoxic hypercapnia (7% CO2-balance O2), however, was the same
      between both groups of pups. These results demonstrate that neonatal IH
      facilitates carotid body sensory response to hypoxia and augments hypoxic
      ventilatory chemoreflex.

PMID- 15258130
TI  - The mouse as a model of cardiovascular adaptations to microgravity.
AB  - There are a multitude of physiological adaptations to microgravity, involving the
      cardiovascular, neuromuscular, and neuroendocrine systems. Some of these
      adaptations lead to cardiovascular deconditioning on return to normal gravity,
      posing a threat to human functional integrity after long-term spaceflight. Animal
      models of microgravity, e.g., tail suspension in rats, have yielded important
      information regarding the mechanism of these adaptations and have been useful in
      the design of countermeasures. The mouse could potentially be a useful
      experimental model, given its small size (smaller and lighter payload) and the
      powerful tools of experimental mouse genetics, which allow us to dissect
      mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide
      range of cardiovascular responses to simulated microgravity, including
      alterations in heart rate, exercise capacity, peripheral arterial vasodilatory
      responsiveness, and baroreflex response. These responses are qualitatively
      similar to many of those demonstrated in humans during spaceflight and in rats
      using tail suspension, although there are some important differences. Thus the
      mouse has value as a model for studies of cardiovascular changes during
      microgravity; however, investigators must maintain an appreciation of important
      species differences.

PMID- 15258131
TI  - Hemoglobin levels in Qinghai-Tibet: different effects of gender for Tibetans vs.
      Han.
AB  - The Tibetan population, long a resident on the Qinghai-Tibetan Plateau, has lower
      hemoglobin concentrations than Han Chinese migrants, but it is incompletely known
      how gender affects the hemoglobin concentrations in the two populations at
      various altitudes. Measurements of hemoglobin concentration were obtained in
      5,887 healthy male and female Tibetan and Han residents aged 5-60 yr, at
      altitudes of 2,664, 3,813, 4,525, and 5,200 m. Multiple regression equations
      showed the beta-coefficients for altitude and for age were higher (P < 0.05) in
      Han men than in Tibetan men and in Han women than in Tibetan women. Analysis
      indicated a significant three-way interaction between altitude, gender, and
      ethnicity (chi2 = 3.72, P = 0.05). With increasing altitude, men progressively
      had more hemoglobin than women in the Han, but not the Tibetan, population. Above
      2,664 m, this gender-related difference in hemoglobin concentration increased
      from childhood to young adulthood more in Han than in Tibetans. We suggest that
      the Han-Tibetan ethnic difference in the effect of altitude on hemoglobin
      concentration depends to a large extent on gender.

PMID- 15258132
TI  - Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase
      activity, and insulin-stimulated glucose transport in rat skeletal muscle.
AB  - We hypothesized that levodopa with carbidopa, a common therapy for patients with
      Parkinson's disease, might contribute to the high prevalence of insulin
      resistance reported in patients with Parkinson's disease. We examined the effects
      of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and
      insulin-stimulated glucose transport in skeletal muscle, the predominant insulin
      responsive tissue. In isolated muscle, levodopa-carbidopa completely prevented
      insulin-stimulated glycogen accumulation and glucose transport. The levodopa
      carbidopa effects were blocked by propranolol, a beta-adrenergic antagonist.
      Levodopa-carbidopa also inhibited the insulin-stimulated increase in glycogen
      synthase activity, whereas propranolol attenuated this effect. Insulin-stimulated
      tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was reduced by
      levodopa-carbidopa, although Akt phosphorylation was unaffected by levodopa
      carbidopa. A single in vivo dose of levodopa-carbidopa increased skeletal muscle
      cAMP concentrations, diminished glycogen synthase activity, and reduced tyrosine
      phosphorylation of IRS-1. A separate set of rats was treated intragastrically
      twice daily for 4 wk with levodopa-carbidopa. After 4 wk of treatment, oral
      glucose tolerance was reduced in rats treated with drugs compared with control
      animals. Muscles from drug-treated rats contained at least 15% less glycogen and
      approximately 50% lower glycogen synthase activity compared with muscles from
      control rats. The data demonstrate beta-adrenergic-dependent inhibition of
      insulin action by levodopa-carbidopa and suggest that unrecognized insulin
      resistance may exist in chronically treated patients with Parkinson's disease.

PMID- 15258134
TI  - Modeling airway resistance dynamics after tidal and deep inspirations.
AB  - Using the forced oscillation technique, we tracked airway resistance continuously
      during quiet breathing (QB) and deep inspiration (DI), thus observing
      fluctuations in resistance that may reflect mechanisms of airway stretch and
      renarrowing. After DI, however, the resistance may be depressed for a period not
      related to volume changes. We hypothesized that this gradual increase in
      resistance after DI-induced dilation was determined by a simple time constant.
      Furthermore, to the extent that this effect reflects dynamic characteristics of
      airway renarrowing, the resistance change after each tidal inspiration should
      also be constrained by this temporal limit. A model relating resistance
      fluctuations to the breathing pattern, including both instantaneous and delayed
      effects, was developed and applied to data from 14 nonasthmatic and 17 asthmatic
      subjects (forced expiratory volume in 1 s = 103 +/- 13 and 83 +/- 12%,
      respectively, means +/- SD) after methacholine challenge (dose 145 +/- 80 and 3.0
      +/- 3.4 micromol, respectively) that resulted in respective forced expiratory
      volume in 1 s reductions of 16 +/- 7 and 24 +/- 6% from baseline. Resistance was
      measured continuously for 1 min of QB, a DI, followed by a further minute of QB.
      Resistance values at end expiration (Ree) and end inspiration were calculated. We
      found that the sequence of Ree after DI was best modeled by a power-law function
      of time rather than an exponential decay (r2 = 0.82 +/- 0.18 compared with 0.63
      +/- 0.16; P < 0.01). Furthermore, the coefficient characterizing this
      "renarrowing function" was close to equal to the coefficient characterizing the
      equivalent function of resistance change between each resistance value at end
      inpiration and subsequent Ree during QB, particularly in the nonasthmatic
      subjects for whom the intraclass correlation was 0.66. This suggests that the
      same time-dependent factors determine renarrowing after both large and small
      breaths.

PMID- 15258133
TI  - Reduction in airway hyperresponsiveness to methacholine by the application of RF
      energy in dogs.
AB  - We delivered controlled radio frequency energy to the airways of anesthetized,
      ventilated dogs to examine the effect of this treatment on reducing airway
      narrowing caused by a known airway constrictor. The airways of 11 dogs were
      treated with a specially designed bronchial catheter in three of four lung
      regions. Treatments in each of the three treated lung regions were controlled to
      a different temperature (55, 65, and 75 degrees C); the untreated lung region
      served as a control. We measured airway responsiveness to local methacholine
      chloride (MCh) challenge before and after treatment and examined posttreatment
      histology to 3 yr. Treatments controlled to 65 degrees C as well as 75 degrees C
      persistently and significantly reduced airway responsiveness to local MCh
      challenge (P < or = 0.022). Airway responsiveness (mean percent decrease in
      airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was
      79 +/- 2.2% in control airways vs. 39 +/- 2.6% (P < or = 0.001) for airways
      treated at 65 degrees C, and 26 +/- 2.7% (P < or = 0.001) for airways treated at
      75 degrees C. Treatment effects were confined to the airway wall and the
      immediate peribronchial region on histological examination. Airway responsiveness
      to local MCh challenge was inversely correlated to the extent of altered airway
      smooth muscle observed in histology (r = -0.54, P < 0.001). We conclude that the
      temperature-controlled application of radio frequency energy to the airways can
      reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway
      smooth muscle contractility.

PMID- 15258135
TI  - Osmolytes induce structure in an early intermediate on the folding pathway of
      barstar.
AB  - Osmolytes stabilize proteins against denaturation, but little is known about how
      their stabilizing effect might affect a protein folding pathway. Here, we report
      the effects of the osmolytes, trimethylamine-N-oxide, and sarcosine on the
      stability of the native state of barstar as well as on the structural
      heterogeneity of an early intermediate ensemble, IE, on its folding pathway. Both
      osmolytes increase the stability of the native protein to a similar extent, with
      stability increasing linearly with osmolyte concentration. Both osmolytes also
      increase the stability of IE but to different extents. Such stabilization leads
      to an acceleration in the folding rate. Both osmolytes also alter the structure
      of IE but do so differentially; the fluorescence and circular dichroism
      properties of IE differ in the presence of the different osmolytes. Because these
      properties also differ from those of the unfolded form in refolding conditions,
      different burst phase changes in the optical signals are seen for folding in the
      presence of the different osmolytes. An analysis of the urea dependence of the
      burst phase changes in fluorescence and circular dichroism demonstrates that the
      formation of IE is itself a multistep process during folding and that the two
      osmolytes act by stabilizing, differentially, different structural components
      present in the IE ensemble. Thus, osmolytes can alter the basic nature of a
      protein folding pathway by discriminating, through differential stabilization,
      between different members of an early intermediate ensemble, and in doing so,
      they thereby appear to channel folding along one route when many routes are
      available.

PMID- 15258136
TI  - High dissociation rate constant of ferrous-dioxy complex linked to the catalase
      like activity in lactoperoxidase.
AB  - Heme reduction of ferric lactoperoxidase (LPO) into its ferrous form initially
      leads to the accumulation of the unstable form of LPO-Fe(II), which spontaneously
      converts to a more stable species, the two of which can be identified by Soret
      peaks at 440 and 434 nm, respectively. Our data demonstrate that both LPO-Fe(II)
      species are capable of binding O(2) at a similar rate to generate the ferrous
      dioxy complex. Its formation with respect to O(2) was first order and monophasic
      and with rate constants of k(on) = 3.8 x 10(4) m(-1) s(-1) and k(off) = 11.2 s(
      1). The dissociation rate constant for the formation of LPO-Fe(II)-O(2) is
      relatively high, in contrast to hemoprotein model compounds. This high
      dissociation rate can be attributed to a combination of effects that include the
      positive trans effect of the proximal ligand, the heme pocket environment, and
      the geometry of the Fe-O(2) linkage. Our results have also shown that the decay
      of the LPO-Fe(II)-O(2) complex occurs by two sequential O(2)-independent steps.
      The first step involves formation of a short-lived intermediate that can be
      characterized by its Soret absorption peak at 416 nm and may be attributed to the
      weakening of the Fe(II)-O(2) linkage with a rate constant of 0.5 s(-1). The
      second step is spontaneous conversion of this intermediate to generate the native
      enzyme and presumably superoxide as end products with a rate constant of 0.03 s(
      1). A comprehensive kinetic model that links LPO-Fe(II)-O(2) complex formation to
      the LPO catalase-like activity, combined with the classic catalytic cycle, is
      presented here.

PMID- 15258137
TI  - Definition of protein kinase sequence motifs that trigger high affinity binding
      of Hsp90 and Cdc37.
AB  - Hsp90 cooperates with its co-chaperone Cdc37 to provide obligatory support to
      numerous protein kinases involved in the regulation of cellular signal
      transduction pathways. In this report, the crystal structure of the Src family
      tyrosine kinase Lck was used to guide the creation of kinase constructs to
      determine features recognized by Hsp90 and its "kinase-specific" co-chaperone
      Cdc37. Two parameters were assayed: the ability and extent to which the
      constructs bound to Hsp90 and Cdc37, and the ability of the constructs to trigger
      salt-resistant high affinity complexes with Hsp90 and Cdc37 independent of the
      presence of molybdate. Although Hsp90 interacted with both the N-terminal and C
      terminal lobes (NL and CL, respectively) of the catalytic domains of the kinases,
      the lobes themselves were not sufficient to trigger the high affinity binding of
      Hsp90. Only constructs containing a complete N- or C-terminal lobe and part of
      the adjacent lobe bound to Hsp90 and Cdc37 in salt-stable complexes independent
      of molybdate. The two minimum constructs that bound Hsp90 and Cdc37 contained the
      alpha-C-helix and the beta4- and beta5-strands of the NL through to end of the CL
      and the NL through to the alpha-E-helix and the amino acids that cap the helix.
      Cdc37 interacted with only the NL and minimally required the alpha-C-helix and
      beta4- and beta5-strands of this lobe of Lck. The results indicate that the high
      affinity binding activity of Hsp90 is triggered through its interaction with
      adjacent subdomain structures of kinase catalytic domains. Furthermore, the alpha
      C-helix and part of its adjoining loop connection to the beta4-strand appear to
      be the primary determinants recognized by Cdc37.

PMID- 15258138
TI  - Radical rebound mechanism in cytochrome P-450-catalyzed hydroxylation of the
      multifaceted radical clocks alpha- and beta-thujone.
AB  - Alpha-thujone (1alpha) and beta-thujone (1beta) were used to investigate the
      mechanism of hydrocarbon hydroxylation by cytochromes P-450(cam) (CYP101) and P
      450(BM3) (CYP102). The thujones are hydroxylated by these enzymes at various
      positions, but oxidation at C-4 gives rise to both rearranged and unrearranged
      hydroxylation products. Rearranged products result from the formation of a
      radical intermediate that can undergo either inversion of stereochemistry or ring
      opening of the adjacent cyclopropane ring. Both of these rearrangements, as well
      as a C-4 desaturation reaction, are observed. The ring opening clock gives oxygen
      rebound rates that range from 0.2 x 10(10) to 2.8 x 10(10) s(-1) for the
      different substrate and enzyme combinations. The C-4 inversion reaction provides
      independent confirmation of a radical intermediate. The phenol product expected
      if a C-4 cationic rather than radical intermediate is formed is not detected. The
      results are consistent with a two-state process and provide support for a radical
      rebound but not a hydroperoxide insertion mechanism for cytochrome P-450
      hydroxylation.

PMID- 15258139
TI  - Defective acidification of intracellular organelles results in aberrant secretion
      of cathepsin D in cancer cells.
AB  - Aberrant secretion of lysosomal hydrolases such as (pro)cathepsin D (proCD) is a
      common phenotypic change in many human cancers. Here we explore the underlying
      molecular defect(s) and find that MCF-7 breast and CaCo-2 colorectal cancer cells
      that are unable to acidify their endosomal compartments secreted higher amounts
      of proCD than did acidification-competent cancer cell types. The latter secreted
      equivalent amounts of proCD only after dissipation of their organellar pH
      gradients with NH(4)Cl. Assessing the critical steps that resulted in proCD
      secretion revealed that the Golgi-associated sorting receptor for CD, i.e. the
      cation-independent mannose-6-phosphate receptor (MPR300), was aberrantly
      distributed in acidification-defective MCF-7 cells. It accumulated mainly in late
      endosomes and/or lysosomes as a complex with its ligand (proCD or intermediate
      CD), as evidenced by its co-localization with both CD and LAMP-2, a late
      endosome/lysosome marker. Our immunoprecipitation analyses also showed that MCF-7
      cells possessed 7-fold higher levels of receptor-enzyme complexes than did
      acidification-competent cells. NH(4)Cl induced similar receptor redistribution
      into LAMP-2-positive structures in acidification-competent cells but not in MCF-7
      cells. The receptor also recovered its normal Golgi localization upon drug
      removal. Based on these observations, we conclude that defective acidification
      results in the aberrant secretion of proCD in certain cancer cells and interferes
      mainly with the normal disassembly of the receptor-enzyme complexes and efficient
      receptor reutilization in the Golgi.

PMID- 15258140
TI  - The yeast phospholipid N-methyltransferases catalyzing the synthesis of
      phosphatidylcholine preferentially convert di-C16:1 substrates both in vivo and
      in vitro.
AB  - Phosphatidylcholine (PC) is an important and abundant structural component of the
      membranes of eukaryotic cells. In the yeast Saccharomyces cerevisiae, the primary
      route for the biosynthesis of PC consists of three consecutive methylation steps
      of phosphatidylethanolamine (PE) catalyzed by the phospholipid N
      methyltransferases Cho2p and Opi3p. To investigate how these biosynthetic enzymes
      contribute to the composition of the PC species profile, the precursor-product
      relationships between PE and newly synthesized PC were determined at the level of
      the molecular species by using electrospray ionization tandem mass spectrometry
      and stable isotope labeling. In vivo labeling of yeast cells for 10 min with
      [methyl-D3]methionine revealed the preferential methylation of di-C16:1 PE over a
      range of PE species compositions. A similar preferential conversion of di-C16:1
      PE to PC was found in vitro upon incubating isolated microsomes with S
      adenosyl[methyl-D3]methionine. Yeast opi3 and cho2 deletion strains were used to
      distinguish between the substrate selectivities of Cho2p and Opi3p, respectively.
      Both biosynthetic enzymes were found to participate in the speciesselective
      methylation with Cho2p contributing the most. The combined results indicate that
      the selective methylation of PE species by the methyltransferases plays an
      important role in shaping the steady-state profile of PC molecular species in
      yeast.

PMID- 15258141
TI  - Three-dimensional solution structure of the cytoplasmic B domain of the mannitol
      transporter IImannitol of the Escherichia coli phosphotransferase system.
AB  - The solution structure of the cytoplasmic B domain of the mannitol (Mtl)
      transporter (II(Mtl)) from the mannitol branch of the Escherichia coli
      phosphotransferase system has been solved by multidimensional NMR spectroscopy
      with extensive use of residual dipolar couplings. The ordered IIB(Mtl) domain
      (residues 375-471 of II(Mtl)) consists of a four-stranded parallel beta-sheet
      flanked by two helices (alpha(1) and alpha(3)) on one face and helix alpha(2) on
      the opposite face with a characteristic Rossmann fold comprising two right-handed
      beta(1)alpha(1)beta(2) and beta(3)alpha(2)beta(4) motifs. The active site loop is
      structurally very similar to that of the eukaryotic protein tyrosine
      phosphatases, with the active site cysteine (Cys-384) primed in the thiolate
      state (pK(a) < 5.6) for nucleophilic attack at the phosphorylated histidine (His
      554) of the IIA(Mtl) domain through stabilization by hydrogen bonding
      interactions with neighboring backbone amide groups at positions i + 2/3/4 from
      Cys-384 and with the hydroxyl group of Ser-391 at position i + 7. Modeling of the
      phosphorylated state of IIB(Mtl) suggests that the phosphoryl group can be
      readily stabilized by hydrogen bonding interactions with backbone amides in the i
      + 2/4/5/6/7 positions as well as with the hydroxyl group of Ser390 at position i
      + 6. Despite the absence of any significant sequence identity, the structure of
      IIB(Mtl) is remarkably similar to the structures of bovine protein tyrosine
      phosphatase (which contains two long insertions relative to IIB(Mtl)) and the
      cytoplasmic B component of enzyme II(Chb), which fulfills an analogous role to
      IIB(Mtl) in the N,N'-diacetylchitobiose branch of the phosphotransferase system.
      All three proteins utilize a cysteine residue in the nucleophilic attack of a
      phosphoryl group covalently bound to another protein.

PMID- 15258142
TI  - Non-homologous end joining requires that the DNA-PK complex undergo an
      autophosphorylation-dependent rearrangement at DNA ends.
AB  - Repair of chromosome breaks by non-homologous end joining requires the XRCC4
      ligase IV complex, Ku, and the DNA-dependent protein kinase catalytic subunit
      (DNA-PKcs). DNA-PKcs must also retain kinase activity and undergo
      autophosphorylation at six closely linked sites (ABCDE sites). We describe here
      an end-joining assay using only purified components that reflects cellular
      requirements for both Ku and kinase-active DNA-PKcs and investigate the
      mechanistic basis for these requirements. A need for DNA-PKcs autophosphorylation
      is sufficient to explain the requirement for kinase activity, in part because
      autophosphorylation is generally required for end-joining factors to access DNA
      ends. However, DNA-PKcs with all six ABCDE autophosphorylation sites mutated to
      alanine allows access to ends through autophosphorylation of other sites, yet our
      in vitro end-joining assay still reflects the defectiveness of this mutant in
      cellular end joining. In contrast, mutation of ABCDE sites to aspartate, a
      phosphorylation mimic, supports high levels of end joining that is now
      independent of kinase activity. This is likely because DNA-PKcs with aspartate
      substitutions at ABCDE sites allow access to DNA ends while retaining affinity
      for Ku-bound ends and stabilizing recruitment of the XRCC4-ligase IV complex.
      Autophosphorylation at ABCDE sites thus apparently directs a rearrangement of the
      DNA-PK complex that ensures access to broken ends and joining steps are coupled
      together within a synaptic complex, making repair more accurate.

PMID- 15258143
TI  - Structural dynamics controls nitric oxide affinity in nitrophorin 4.
AB  - Nitrophorin 4 (NP4) is one of seven nitric oxide (NO) transporting proteins in
      the blood-sucking insect Rhodnius prolixus. In its physiological function, NO
      binds to a ferric iron centered in a highly ruffled heme plane. Carbon monoxide
      (CO) also binds after reduction of the heme iron. Here we have used Fourier
      transform infrared spectroscopy at cryogenic temperatures to study CO and NO
      binding and migration in NP4, complemented by x-ray cryo-crystallography on xenon
      containing NP4 crystals to identify cavities that may serve as ligand docking
      sites. Multiple infrared stretching bands of the heme-bound ligands indicate
      different active site conformations with varying degrees of hydrophobicity.
      Narrow infrared stretching bands are observed for photodissociated CO and NO;
      temperature-derivative spectroscopy shows that these bands are associated with
      ligand docking sites close to the extremely reactive heme iron. No rebinding from
      distinct secondary sites was detected, although two xenon binding cavities were
      observed in the x-ray structure. Photolysis studies at approximately 200 K show
      efficient NO photoproduct formation in the more hydrophilic, open NP4
      conformation. This result suggests that ligand escape is facilitated in this
      conformation, and blockage of the active site by water hinders immediate
      reassociation of NO to the ferric iron. In the closed, low-pH conformation,
      ligand escape from the active site of NP4 is prevented by an extremely reactive
      heme iron and the absence of secondary ligand docking sites.

PMID- 15258144
TI  - Identification of small molecule synthetic inhibitors of DNA polymerase beta by
      NMR chemical shift mapping.
AB  - DNA polymerase beta (beta-pol) plays a central role in repair of damaged DNA
      bases by base excision repair (BER) pathways. A predominant phenotype of beta-pol
      null mouse fibroblasts is hypersensitivity to the DNA-methylating agent methyl
      methanesulfonate. Residues in the 8-kDa domain of beta-pol that seem to interact
      with a known natural product beta-pol inhibitor, koetjapic acid, were identified
      by NMR chemical shift mapping. The data implicate the binding pocket as the
      hydrophobic cleft between helix-2 and helix-4, which provides the DNA binding and
      deoxyribose phosphate lyase activities of the enzyme. Nine structurally related
      synthetic compounds, containing aromatic or other hydrophobic groups in
      combination with two carboxylate groups, were then tested. They were found to
      bind to the same or a very similar region on the surface of the enzyme. The
      ability of these compounds to potentiate methyl methanesulfonate cytotoxicity, an
      indicator of cellular BER capacity, in wild-type and beta-pol null mouse
      fibroblasts, was next ascertained. The most active and beta-pol-specific of these
      agents, pamoic acid, was further characterized and found to be an inhibitor of
      the deoxyribose phosphate lyase and DNA polymerase activities of purified beta
      pol on a BER substrate. Our results illustrate that NMR-based mapping techniques
      can be used in the design of small molecule enzyme inhibitors including those
      with potential use in a clinical setting.

PMID- 15258145
TI  - A new class of peroxisome proliferator-activated receptor agonists with a novel
      binding epitope shows antidiabetic effects.
AB  - The peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors belonging to the NR1 subfamily of nuclear receptors. The
      PPARs play key roles in the control of glucose and lipid homeostasis, and the
      synthetic isoform-specific PPAR agonists are used clinically to improve insulin
      sensitivity and to lower serum triglyceride levels. All of the previously
      reported PPAR agonists form the same characteristic interactions with the
      receptor, which have been postulated to be important for the induction of
      agonistic activity. Here we describe a new class of PPARalpha/gamma modulators,
      the 5-substituted 2-benzoylaminobenzoic acids (2-BABAs). As shown by x-ray
      crystallography, the representative compounds BVT.13, BVT.762, and BVT.763,
      utilize a novel binding epitope and lack the agonist-characteristic interactions.
      Despite this, some compounds within the 2-BABA family are potent agonists in a
      cell-based reporter gene assay. Furthermore, BVT.13 displays antidiabetic effects
      in ob/ob mice. We concluded that the 2-BABA binding mode can be used to design
      isoform-specific PPAR modulators with biological activity in vivo.

PMID- 15258146
TI  - EPAS1 promotes adipose differentiation in 3T3-L1 cells.
AB  - Adipose differentiation is regulated by several transcription factors, such as
      the CAAT/enhancer-binding protein family and peroxisome proliferator activator
      (PPAR) gamma2. Several recent studies have shown that the basic helix-loop-helix
      PAS superfamily is also involved in the regulation of adipose differentiation. In
      this study, we investigated the roles played by EPAS1 (endothelial PAS domain
      protein 1) in adipogenesis. EPAS1, also referred to as hypoxia-inducible factor
      2alpha, is a transcription factor known to play essential roles in catecholamine
      homeostasis, vascular remodeling, and the maintenance of reactive oxygen species,
      and so forth. During adipose differentiation in 3T3-L1 cells, the level of EPAS1
      mRNA began to increase 6 days after the induction, and EPAS1 was highly expressed
      in differentiated cells. To examine whether EPAS1 is involved in adipogenesis, we
      first isolated stable clones from 3T3-L1 cells in which we could induce the
      expression of an EPAS1 C-terminal deletion mutant (designated EPAS1-(1-485)) with
      the insect hormone. The induction of EPAS1-(1-485) allowed the cells to
      accumulate only minimum amounts of intracellular lipid droplets. Consistent with
      the morphological observations, a minimum amount of aP2 and PPARgamma2 mRNA was
      induced in the EPAS1-(1-485) cells. We then examined whether or not EPAS1 was
      able to promote adipogenesis in NIH 3T3 cells, a relatively nonadipogenic cell
      line. Overexpression of EPAS1 in NIH 3T3 cells induced a significant amount of
      lipid accumulation compared with that of the control cells in the presence of the
      PPARgamma ligand. The results were also confirmed by measuring the expression of
      adipocyte-related genes. Adenovirus-mediated EPAS1-(1-485) expression resulted in
      the reduction of basal and insulin-dependent glucose transport in 3T3-L1
      adipocytes. The mechanism involved the transcriptional regulation of GLUT1,
      GLUT4, and IRS3 expression by EPAS1. Taken together, these results suggest that
      EPAS1 plays several supporting roles in maintaining specific aspects of
      adipogenesis and adipocyte function including regulation of glucose uptake
      followed by lipid synthesis.

PMID- 15258147
TI  - Chronic oxidative stress as a central mechanism for glucose toxicity in
      pancreatic islet beta cells in diabetes.

PMID- 15258148
TI  - Identification of phospholipase C-gamma1 as a mitogen-activated protein kinase
      substrate.
AB  - The discovery of sequence motifs that mediate protein-protein interactions,
      coupled with the availability of protein amino acid sequence data, allows for the
      identification of putative protein binding pairs. The present studies were based
      on our identification of an amino acid sequence in phosphatidylinositol-specific
      phospholipase C-gamma1 (PLC-gamma1) that fits the consensus sequence for a
      mitogen-activated protein kinase (MAPK) binding site, termed the D-domain.
      Extracellular signal-regulated kinase 2 (ERK2), an MAPK, and phospho-ERK2 were
      bound by an immobilized peptide sequence containing the identified PLC-gamma1 D
      domain. Furthermore, a peptide containing the PLC-gamma1 D-domain was able to
      competitively inhibit the in vitro phosphorylation of recombinant PLC-gamma1 by
      recombinant phospho-ERK2, whereas a control peptide derived from a distant region
      of PLC-gamma1 was ineffective. Similarly, the peptide containing the PLC-gamma1 D
      domain, but not the control peptide, competitively inhibited the in vitro
      phosphorylation of Elk-1 and c-Jun catalyzed by recombinant phospho-ERK2 and
      phospho-c-Jun N-terminal kinase 3 (phospho-JNK3), another type of MAPK,
      respectively. Incubation of anti-PLC-gamma1 immunocomplexes isolated from rat
      brain with recombinant phospho-ERK2 opposed the increase in PLC-gamma1-catalyzed
      hydrolysis of phosphatidylinositol 4,5-P(2) (PtdIns(4,5)P(2)), which was produced
      by a tyrosine kinase associated with the immunocomplexes, whereas in vitro
      phosphorylation of recombinant PLC-gamma1 by recombinant phospho-ERK2 did not
      alter PLC-gamma1-catalyzed PtdIns(4,5)P(2) hydrolysis. These studies have
      uncovered a previously unidentified mechanism for the integration of PLC-gamma1-
      and ERK2-dependent signaling.

PMID- 15258149
TI  - Hyper-responsiveness to stimulation of human immunodeficiency virus-infected CD4+
      T cells requires Nef and Tat virus gene products and results from higher NFAT, NF
      kappaB, and AP-1 induction.
AB  - A chronic state of immune hyperactivation is a feature of human immunodeficiency
      virus type-1 (HIV-1) infection. Studies on the molecular mechanisms by which HIV
      1 can modulate the activation state of T cells indicate that both Nef and Tat can
      alter T cell activation. However, the vast majority of data has been obtained
      from experiments performed with vectors encoding a single virus protein. We
      demonstrate that infection of human CD4(+) T lymphocytes with fully infectious
      HIV-1 leads to a hyper-responsiveness of the interleukin-2 promoter.
      Hypersensitivity in HIV-1-infected T cells was observed upon stimulation with
      various agents that are engaging different signal transduction pathways.
      Experiments performed with recombinant heat stable antigen-encoding HIV-1
      indicated that the virus-infected cells are the cells with an enhanced response.
      Both Nef and Tat are involved in this virus-mediated enhancing effect on
      interleukin-2 promoter activity. Interestingly, whereas Nef seems to be acting
      mainly through hyperactivation of nuclear factor of activated T cells (NFAT), Tat
      acts in an NFAT-independent manner. Mobility shift experiments demonstrated that
      the HIV-1-associated priming of human T cells for stimulation results in a
      greater induction of transcription factors recognized as essential players in T
      cell activation, i.e. NFAT, NF-kappaB, and AP-1. A hyper-responsive state was
      also established upon HIV-1 infection of a more natural cellular reservoir, i.e.
      primary CD4(+) T lymphocytes. Considering that the HIV-1 life cycle is tightly
      regulated by the T cell signaling machinery, the priming for activation of a
      major viral reservoir represents a means by which this retrovirus can create an
      ideal cellular microenvironment for its propagation and maintenance.

PMID- 15258150
TI  - Kaposi's sarcoma-associated herpesvirus-encoded viral interleukin-6 is secreted
      and modified differently than human interleukin-6: evidence for a unique
      autocrine signaling mechanism.
AB  - Viral interleukin-6 (vIL-6) is a homolog of cellular IL-6 that is encoded by the
      Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 binds to the IL-6
      signal transducer gp130 without the cooperation of the IL-6 high affinity
      receptor to induce STAT3 DNA binding and cell proliferation. Although vIL-6 is
      believed to be important in the pathogenesis of KSHV-induced diseases, its
      secretion and post-translational modifications have not previously been
      characterized. Pulse-chase analysis revealed that the half-time of vIL-6
      secretion is approximately 8-fold longer than that of human IL-6. Yet, the vIL-6
      signal sequence targets human IL-6 secretion to nearly wild-type levels.
      Surprisingly, vIL-6 was not secreted from a cell line that does not express gp130
      but expression of human gp130 in these cells enabled the secretion of vIL-6.
      Consistent with this observation, complete maturation of gp130 N-glycans is
      inhibited by vIL-6 coexpression, suggesting that the binding of the receptor to
      vIL-6 occurs intracellularly in early or pre-Golgi compartments. Furthermore, a
      vIL-6 mutant containing an endoplasmic reticulum retention signal is not secreted
      but does still induce receptor activation and signaling. Secreted vIL-6 is
      completely glycosylated at both possible N-glycosylaton sites and contains a
      large proportion of immature high-mannose glycans that is not typical of
      cytokines. These findings suggest that vIL-6 may induce gp130 signaling by an
      exclusively autocrine mechanism that relies on intracellular binding to its
      receptor. During KSHV infection, vIL-6 may only induce signaling in KSHV-infected
      cells to benefit the viral life cycle and promote oncogenic transformation.

PMID- 15258151
TI  - Oligomeric state of the Escherichia coli metal transporter YiiP.
AB  - YiiP is a 32.9-kDa metal transporter found in the plasma membrane of Escherichia
      coli (Chao, Y., and Fu, D. (2004) J. Biol. Chem. 279, 17173-17180). Here we
      report the determination of the YiiP oligomeric state in detergent-lipid micelles
      and in membranes. Molecular masses of YiiP solubilized with dodecyl-, undecyl-,
      decyl-, or nonyl-beta-d-maltoside were measured directly using size-exclusion
      chromatography coupled with laser light-scattering photometry, yielding a mass
      distribution of YiiP homo-oligomers within a narrow range (68.0-68.8 kDa) that
      equals the predicted mass of a YiiP dimer within experimental error. The
      detergent-lipid masses associated with YiiP in the mixed micelles were found to
      increase from 135.5 to 232.6 kDa, with an apparent correlation with the alkyl
      chain length of the maltoside detergents. Cross-linking the detergent-solubilized
      YiiP with 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC)
      resulted in a dimeric cross-linked product in an EDC concentration-dependent
      manner. The oligomeric state of the purified YiiP in reconstituted membranes was
      determined by electron microscopic analysis of two-dimensional YiiP crystals in
      negative stain. A projection structure calculated from measurable optical
      diffractions to 25 A revealed a pseudo-2-fold symmetry within a molecular
      boundary of approximately 75 x 40 A, indicative of the presence of YiiP dimers in
      membranes. These data provide direct structural evidence for a dimeric
      association of YiiP both in detergent-lipid micelles and in the reconstituted
      lipid bilayer. The functional relevance of the dimeric association in YiiP is
      discussed.

PMID- 15258152
TI  - Oligomerization, chaperone activity, and nuclear localization of p26, a small
      heat shock protein from Artemia franciscana.
AB  - Artemia franciscana embryos undergo encystment, developmental arrest and
      diapause, the last characterized by profound metabolic dormancy and extreme
      stress resistance. Encysted embryos contain an abundant small heat shock protein
      termed p26, a molecular chaperone that undoubtedly has an important role in
      development. To understand better the role of p26 in Artemia embryos, the
      structural and functional characteristics of full-length and truncated p26
      expressed in Escherichia coli and COS-1 cells were determined. p26 chaperone
      activity declined with increasing truncation of the protein, and those deletions
      with the greatest adverse effect on protection of citrate synthase during thermal
      stress had the most influence on oligomerization. When produced in either
      prokaryotic or eukaryotic cells the p26 alpha-crystallin domain consisting of
      amino acid residues 61-152 existed predominantly as monomers, and p26 variants
      lacking the amino-terminal domain but with intact carboxyl-terminal extensions
      were mainly monomers and dimers. The amino terminus was, therefore, required for
      efficient dimer formation. Assembly of higher order oligomers was enhanced by the
      carboxyl-terminal extension, although removing the 10 carboxyl-terminal residues
      had relatively little effect on oligomerization and chaperoning. Full-length and
      carboxyl-terminal truncated p26 resided in the cytoplasm of transfected COS-1
      cells; however, variants missing the complete amino-terminal domain and existing
      predominantly as monomers/dimers entered the nuclei. A mechanism whereby oligomer
      disassembly assisted entry of p26 into nuclei was suggested, this of importance
      because p26 translocates into Artemia embryo nuclei during development and
      stress. However, when examined in Artemia, the p26 oligomer size was unchanged
      under conditions that allowed movement into nuclei, suggesting a process more
      complex than just oligomer dissociation.

PMID- 15258153
TI  - Changes in the mitochondrial proteome during the anoxia to air transition in rice
      focus around cytochrome-containing respiratory complexes.
AB  - The ability of rice seedlings to grow from dry seed under anoxia provides a rare
      opportunity in a multicellular eukaryote to study the stages of mitochondrial
      biogenesis triggered by oxygen availability. The function and proteome of rice
      mitochondria synthesized under 6 days of anoxia following 1 day of air adaptation
      have been compared with mitochondria isolated from 7-day aerobically grown rice
      seedlings. Rice coleoptiles grown under anoxia, and the mitochondria isolated
      from them respired very slowly compared with air-adapted and air-grown seedlings.
      Immunodetection of key mitochondrial protein markers, isoelectric focusing
      electrophoresis followed by SDS-PAGE to make soluble mitochondria proteome maps,
      and shotgun sequencing of mitochondrial proteins by liquid chromatography-tandem
      mass spectrometry all revealed similar patterns of the major function categories
      of mitochondrial proteins from both anoxic and air-adapted samples. Activity
      analysis showed respiratory oxidases markedly increased in activity during the
      air adaptation of seedlings. Blue-native electrophoresis followed by SDS-PAGE of
      mitochondrial membrane proteins clearly showed the very low abundance of
      assembled b/c complex and cytochrome c(1) oxidase complex in the mitochondrial
      membrane in anoxic samples and the dramatic increase in the abundance of these
      complexes on air adaptation. Total heme content, cytochrome absorbance spectra,
      and the electron carrier, cytochrome c, also increased markedly on air
      adaptation. These results likely reflect limited heme synthesis for cytochrome
      assembly in the absence of oxygen and represent a discrete and reversible
      blockage of full mitochondrial biogenesis in this anoxia-tolerant species.

PMID- 15258154
TI  - Interleukin (IL)-4-independent maintenance of histone modification of the IL-4
      gene loci in memory Th2 cells.
AB  - Interleukin (IL)-4-induced STAT6 activation and the subsequent up-regulation of
      GATA3 are crucial for the induction of chromatin remodeling of the Th2 cytokine
      gene loci as Th2 cells undergo development. This study probes the role of these
      molecules in the maintenance of memory Th2 cells. IL-4 was not required to
      maintain the capability for Th2 cytokine production in in vivo generated antigen
      specific memory Th2 cells. Histone H3-K9/14 hyperacetylation and intergenic
      transcripts associated with the IL-4 gene locus were preserved in the absence of
      IL-4, but those associated with the IL-13 gene were partially IL-4-dependent.
      Histone H3-K4 methylation of the IL-13 and IL-4 gene loci was fully preserved in
      memory Th2 cells and accompanied by memory cell-specific accumulation of Pol II
      complex to highly restricted sites. Thus, memory Th2 cells maintain a unique Th2
      specific remodeled chromatin in the IL-4 and IL-13 gene loci by active molecular
      events that are IL-4-independent.

PMID- 15258155
TI  - Crystal structure of human bisphosphoglycerate mutase.
AB  - Bisphosphoglycerate mutase is a trifunctional enzyme of which the main function
      is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin.
      The gene coding for bisphosphoglycerate mutase from the human cDNA library was
      cloned and expressed in Escherichia coli. The protein crystals were obtained and
      diffract to 2.5 A and produced the first crystal structure of bisphosphoglycerate
      mutase. The model was refined to a crystallographic R-factor of 0.200 and R(free)
      of 0.266 with excellent stereochemistry. The enzyme remains a dimer in the
      crystal. The overall structure of the enzyme resembles that of the cofactor
      dependent phosphoglycerate mutase except the regions of 13-21, 98-117, 127-151,
      and the C-terminal tail. The conformational changes in the backbone and the side
      chains of some residues reveal the structural basis for the different activities
      between phosphoglycerate mutase and bisphosphoglycerate mutase. The
      bisphosphoglycerate mutase-specific residue Gly-14 may cause the most important
      conformational changes, which makes the side chain of Glu-13 orient toward the
      active site. The positions of Glu-13 and Phe-22 prevent 2,3-bisphosphoglycerate
      from binding in the way proposed previously. In addition, the side chain of Glu
      13 would affect the Glu-89 protonation ability responsible for the low mutase
      activity. Other structural variations, which could be connected with functional
      differences, are also discussed.

PMID- 15258156
TI  - Hypotonicity-induced exocytosis of the skate anion exchanger skAE1: role of lipid
      raft regions.
AB  - Upon hypotonic volume expansion, skate erythrocytes lose solutes via a pathway
      that requires participation of anion exchangers (AEs). Three skate AE isoforms
      (skAEs) are expressed, and at least skAE1 has been shown to mediate this effect
      when expressed in oocytes. Under isoosmotic conditions, only a small fraction of
      skAE1 is expressed on the external plasma membrane. Under these conditions, a
      portion of skAE1 may be found in non-ionic detergent-insoluble regions. However,
      the detergent-insoluble material is found intracellularly. Cellular volume
      expansion by hypoosmotic volume expansion but not volume expansion by isoosmotic
      medium by permeant solutes (ethylene glycol, diethyl urea, or ammonium chloride)
      stimulates the appearance of skAE1 in the external plasma membrane, and a
      significant portion of this is found in detergent-insoluble regions. Upon
      hypoosmotic volume expansion nearly half of the skAE1 is found as oligomers.
      SkAE1 in these detergent-insoluble fractions is highly tyrosine phosphorylated.
      These data suggest that volume expansion by hypoosmotic medium stimulates
      movement of skAE1 from an intracellular pool contained in detergent-insoluble
      lipid rafts to the plasma membrane. This skAE1 associates to form oligomers that
      could be involved in the solute efflux that occurs upon volume expansion.

PMID- 15258157
TI  - Evidence for activation of endogenous transporters in Xenopus laevis oocytes
      expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT.
AB  - A large body of genetic, reverse genetic, and epidemiological data has linked
      chloroquine-resistant malaria to polymorphisms within a gene termed pfcrt in the
      human malarial parasite Plasmodium falciparum. To investigate the biological
      function of the chloroquine resistance transporter, PfCRT, as well as its role in
      chloroquine resistance, we functionally expressed this protein in Xenopus laevis
      oocytes. Our data show that PfCRT-expressing oocytes exhibit a depolarized
      resting membrane potential and a higher intracellular pH compared with control
      oocytes. Pharmacological and electrophysiological studies link the higher
      intracellular pH to an enhanced amiloride-sensitive H(+) extrusion and the low
      membrane potential to an activated nonselective cation conductance. The finding
      that both properties are independent of each other, together with the fact that
      they are endogenously present in X. laevis oocytes, supports a model in which
      PfCRT activates transport systems. Our data suggest that PfCRT plays a role as a
      direct or indirect activator or modulator of other transporters.

PMID- 15258158
TI  - Up-regulation of neurohemerythrin expression in the central nervous system of the
      medicinal leech, Hirudo medicinalis, following septic injury.
AB  - We report here some results of a proteomic analysis of changes in protein
      expression in the leech Hirudo medicinalis in response to septic injury.
      Comparison of two-dimensional protein gels revealed several significant
      differences between normal and experimental tissues. One protein found to be up
      regulated after septic shock was identified, through a combination of Edman
      degradation, mass spectrometry, and molecular cloning, as a novel member of the
      hemerythrin family, a group of non-heme-iron oxygen transport proteins found in
      four invertebrate phyla: sipunculids, priapulids, brachiopods, and annelids. We
      found by in situ hybridization and immunocytochemistry that the new leech
      protein, which we have called neurohemerythrin, is indeed expressed in the leech
      central nervous system. Both message and protein were detected in the pair of
      large glia within the ganglionic neuropile, in the six packet glia that surround
      neuronal somata in each central ganglion, and in the bilateral pair of glia that
      separate axonal fascicles in the interganglionic connective nerves. No expression
      was detected in central neurons or in central nervous system microglia.
      Expression was also observed in many other, non-neuronal tissues in the body
      wall. Real-time PCR experiments suggest that neurohemerythrin is up-regulated
      posttranscriptionaly. We consider potential roles of neurohemerythrin, associated
      with its ability to bind oxygen and iron, in the innate immune response of the
      leech nervous system to bacterial invasion.

PMID- 15258159
TI  - The hydrodynamic properties of dark- and light-activated states of n-dodecyl beta
      D-maltoside-solubilized bovine rhodopsin support the dimeric structure of both
      conformations.
AB  - Rhodopsin (Rho) has been extracted in n-dodecyl beta-D-maltoside (DM) from bovine
      retinal rod outer segments and purified to homogeneity by affinity chromatography
      on concanavalin A-Sepharose. Because chemical cross-linking of Rho and
      photoactivated Rho (Rho*) provided initial evidence for the oligomeric nature of
      the photoreceptor protein, we carried out a hydrodynamic characterization of the
      native and activated conformations of detergent-solubilized Rho. The molecular
      weights of the complexes between dark and photoexcited states of Rho and DM were
      determined by gel filtration chromatography on Sephacryl S-300, in the presence
      of 0.1% DM. Subtracting the size of the corresponding detergent micelles resulted
      in molecular masses of 78 kDa for native Rho and 76 kDa for Rho*. The measured
      content of 0.97 g of detergent/g of protein resulted in a calculated partial
      specific volume of 0.765 cm(3)/g for the protein-detergent complex and a molar
      mass of 64-65 kDa for the protein moiety. The sizes of Rho.DM and Rho*.DM
      complexes were also evaluated by sedimentation on 10-30% sucrose gradients, in
      the presence of 0.1% DM, and molecular masses of about 60 kDa were estimated for
      both the dark- and light-activated states of the photoreceptor protein. The size
      of Rho was determined to be 65,300 and 69,800 Da, respectively, when the purified
      Rho.DM complex was either chromatographed on Sephacryl S-300 or ultracentrifuged
      on sucrose gradients in the absence of DM. All these results were consistent with
      a dimeric quaternary structure for both conformations of Rho. Additionally, the
      functional integrity of the purified photoreceptor protein following gel
      filtration chromatography and ultracentrifugation was demonstrated by three
      criteria as follows: (i) its characteristic UV-visible absorption spectra, (ii)
      its capability to photoactivate transducin, and (iii) its ability to serve as a
      substrate for rhodopsin kinase.

PMID- 15258160
TI  - Endogenous nitration of iron regulatory protein-1 (IRP-1) in nitric oxide
      producing murine macrophages: further insight into the mechanism of nitration in
      vivo and its impact on IRP-1 functions.
AB  - Iron regulatory protein-1 (IRP-1) is a bifunctional [4Fe-4S] protein that
      functions as a cytosolic aconitase or as a trans-regulatory factor controlling
      iron homeostasis at a post-transcriptional level. Because IRP-1 is a sensitive
      target protein for nitric oxide (NO), we investigated whether this protein is
      nitrated in inflammatory macrophages and whether this post-transcriptional
      modification changes its activities. RAW 264.7 macrophages were first stimulated
      with interferon-gamma and lipopolysaccharide (IFN-gamma/LPS) and then triggered
      by phorbol 12-myristate 13-acetate (PMA) in order to promote co-generation of NO*
      and O*2-.. IRP-1 was isolated by immunoprecipitation and analyzed for protein
      bound nitrotyrosine by Western blotting. We show that nitration of endogenous IRP
      1 in NO-producing macrophages boosted to produce O*2- was accompanied by
      aconitase inhibition and impairment of its capacity to bind the iron-responsive
      element (IRE) of ferritin mRNA. Lost IRE-binding activity was not recovered by
      exposure of IRP-1 to 2% 2-mercaptoethanol and was not due to protein degradation.
      Inclusion of cis-aconitate with cell extract to stabilize the [4Fe-4S] cluster of
      holo-IRP-1 rendered protein insensitive to nitration by peroxynitrite, suggesting
      that loss of [Fe-S] cluster and subsequent change of conformation are
      prerequisites for tyrosine nitration. IRP-1 nitration was strongly reduced when
      IFN-gamma/LPS/PMA-stimulated cells were incubated with myeloperoxidase
      inhibitors, which points to the contribution of the nitrite/H2O2/peroxidase
      pathway to IRP-1 nitration in vivo. Interestingly, under these conditions, IRP-1
      recovered full IRE binding as assessed by treatment with 2% 2-mercaptoethanol.
      Peroxidase-mediated nitration of critical tyrosine residues, by holding IRP-1 in
      an inactive state, may constitute, in activated macrophages, a self-protecting
      mechanism against iron-induced toxicity.

PMID- 15258161
TI  - Analysis of the set of GABA(A) receptor genes in the human genome.
AB  - The genes of the ionotropic gamma-aminobutyric acid receptor (GABR) subunits have
      shown an unusual chromosomal clustering, but only now can this be fully specified
      by analyses of the human genome. We have characterized the genes encoding the 18
      known human GABR subunits, plus one now located here, for their precise
      locations, sizes, and exon/intron structures. Clusters of 17 of the 19,
      distributed between five chromosomes, are specified in detail, and their possible
      significance is considered. By applying search algorithms designed to recognize
      sequences of all known GABR-type subunits in species from man down to nematodes,
      we found no new GABR subunit is detectable in the human genome. However, the
      sequence of the human orthologue of the rat GABR rho3 receptor subunit was
      uncovered by these algorithms, and its gene could be analyzed. Consistent with
      those search results, orthologues of the beta4 and gamma4 subunits from the
      chicken, not cloned from mammals, were not detectable in the human genome by
      specific searches for them. The relationships are consistent with the mammalian
      subunit being derived from the beta line and epsilon from the gamma line, with
      mammalian loss of beta4 and gamma4. In their structures the human GABR genes show
      a basic pattern of nine coding exons, with six different genomic mechanisms for
      the alternative splicing found in various subunits. Additional noncoding exons
      occur for certain subunits, which can be regulatory. A dicysteine loop and its
      exon show remarkable constancy between all GABR subunits and species, of deduced
      functional significance.

PMID- 15258162
TI  - The structure of human microsomal cytochrome P450 3A4 determined by X-ray
      crystallography to 2.05-A resolution.
AB  - The structure of P450 3A4 was determined by x-ray crystallography to 2.05-A
      resolution. P450 3A4 catalyzes the metabolic clearance of a large number of
      clinically used drugs, and a number of adverse drug-drug interactions reflect the
      inhibition or induction of the enzyme. P450 3A4 exhibits a relatively large
      substrate-binding cavity that is consistent with its capacity to oxidize bulky
      substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics.
      Family 3A P450s also exhibit unusual kinetic characteristics that suggest
      simultaneous occupancy by smaller substrates. Although the active site volume is
      similar to that of P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity
      differs considerably due to differences in the folding and packing of portions of
      the protein that form the cavity. Compared with P450 2C8, the active site cavity
      of 3A4 is much larger near the heme iron. The lower constraints on the motions of
      small substrates near the site of oxygen activation may diminish the efficiency
      of substrate oxidation, which may, in turn, be improved by space restrictions
      imposed by the presence of a second substrate molecule. The structure of P450 3A4
      should facilitate a better understanding of the substrate selectivity of the
      enzyme.

PMID- 15258163
TI  - RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by
      insulin.
AB  - Stimulation of glucose transport by insulin in cultured adipocytes through
      translocation of intracellular GLUT4 glucose transporters to the plasma membrane
      has been suggested to require phosphatidylinositol (PI) 3-kinase-dependent and
      independent mechanisms. To test the involvement of a PI 3-kinase-independent
      pathway leading to activation of the TC10 GTPase, the putative intermediates CAP,
      c-Cbl, Cbl-b, and CrkII were selectively depleted in 3T3-L1 adipocytes using
      highly efficient small interfering (si) RNAs. Simultaneous depletion of the
      ubiquitination factors c-Cbl plus Cbl-b in cultured adipocytes had the expected
      effect of delaying dephosphorylation of EGF receptors upon removal of EGF.
      However, siRNA-mediated gene silencing of both Cbl isoforms or CAP or CrkII in
      these cells failed to attenuate insulin-stimulated deoxyglucose transport or Myc
      tagged GLUT4-GFP translocation at either sub-maximal or maximal concentrations of
      insulin. The dose-response relationship for insulin stimulation of deoxyglucose
      transport in primary adipocytes derived from c-Cbl knock-out mice was also
      identical to insulin action on adipocytes from wild type mice. These data are
      consistent with the hypothesis that CAP, Cbl iso-forms, and CrkII are not
      required components of insulin signaling to GLUT4 transporters.

PMID- 15258164
TI  - Interactions between selenium and sulphur nutrition in Arabidopsis thaliana.
AB  - Selenium (Se) is an essential plant micronutrient, but is toxic at high tissue
      concentrations. It is chemically similar to sulphur (S), an essential plant
      macronutrient. The interactions between Se and S nutrition were investigated in
      the model plant Arabidopsis thaliana (L.) Heynh. Arabidopsis plants were grown on
      agar containing a complete mineral complement and various concentrations of
      selenate and sulphate. The Se/S concentration ratio in the shoot
      ([Se](shoot)/[S](shoot)) showed a complex dependence on the ratio of selenate to
      sulphate concentration in the agar ([Se](agar)/[S](agar)). Increasing [S](agar)
      increased shoot fresh weight (FW) and [S](shoot), but decreased [Se](shoot).
      Increasing [Se](agar) increased both [Se](shoot) and [S](shoot), but reduced
      shoot FW. The reduction in shoot FW in the presence of Se was linearly related to
      the shoot Se/S concentration ratio. These data suggest (i) that Se and S enter
      Arabidopsis through multiple transport pathways with contrasting
      sulphate/selenate selectivities, whose activities vary between plants of
      contrasting nutritional status, (ii) that rhizosphere sulphate inhibits selenate
      uptake, (iii) that rhizosphere selenate promotes sulphate uptake, possibly by
      preventing the reduction in the abundance and/or activity of sulphate
      transporters by sulphate and/or its metabolites, and (iv) that Se toxicity occurs
      because Se and S compete for a biochemical process, such as assimilation into
      amino acids of essential proteins.

PMID- 15258165
TI  - NtWBC1, an ABC transporter gene specifically expressed in tobacco reproductive
      organs.
AB  - To identify genes specifically or predominantly expressed in the stigmas/styles
      and to establish their possible function in the reproductive process of plants, a
      tobacco stigma/style cDNA library was constructed and differentially screened,
      resulting in the isolation of several cDNA clones. The molecular characterization
      of one of these clones is described here. After sequencing the cDNA and the
      isolated genomic clone, it was determined that the corresponding gene encodes a
      protein containing an ATP-binding cassette, characteristic of ABC transporters.
      This gene, designated as NtWBC1 (Nicotiana tabacum ABC transporter of the White
      Brown Complex subfamily), encodes a protein that contains the typical structure
      of the 'half-transporters' of the White subfamily. To establish the spatial
      expression pattern of the NtWBC1 gene, northern blot and real-time RT-PCR
      analyses with total RNA from roots, stems, leaves, sepals, petals, stamens,
      stigmas/styles, ovaries, and seeds were performed. The result revealed a
      transcript of 2.5 kb present at high levels in stigmas and styles and a smaller
      transcript (2.3 kb) present at a lower level in stamens. NtWBC1 expression is
      developmentally regulated in stigmas/styles, with mRNA accumulation increasing
      toward anthesis. In situ hybridization experiments demonstrated that NtWBC1 is
      expressed in the stigmatic secretory zone and in anthers, at the stomium region
      and at the vascular bundle. NtWBC1 is the first ABC transporter gene with
      specific expression in plant reproductive organs to be identified and its
      expression pattern suggests important role(s) in the reproductive process.

PMID- 15258166
TI  - Applications of chlorophyll fluorescence can improve crop production strategies:
      an examination of future possibilities.
AB  - Chlorophyll fluorescence has been routinely used for many years to monitor the
      photosynthetic performance of plants non-invasively. The relationships between
      chlorophyll fluorescence parameters and leaf photosynthetic performance are
      reviewed in the context of applications of fluorescence measurements to screening
      programmes which seek to identify improved plant performance. The potential role
      of chlorophyll fluorescence imaging in increasing both the sensitivity and
      throughput of plant screening programmes is examined. Finally, consideration is
      given to possible specific applications of chlorophyll fluorescence for screening
      of plants for tolerance to environmental stresses and for improvements in
      glasshouse production and post-harvest handling of crops.

PMID- 15258167
TI  - Mitochondria are the main target for oxidative damage in leaves of wheat
      (Triticum aestivum L.).
AB  - Photosynthesis, respiration, and other processes produce reactive oxygen species
      (ROS) that can cause oxidative modifications to proteins, lipids, and DNA. The
      production of ROS increases under stress conditions, causing oxidative damage and
      impairment of normal metabolism. In this work, oxidative damage to various
      subcellular compartments (i.e. chloroplasts, mitochondria, and peroxisomes) was
      studied in two cultivars of wheat differing in ascorbic acid content, and growing
      under good irrigation or drought. In well-watered plants, mitochondria contained
      9-28-fold higher concentrations of oxidatively modified proteins than
      chloroplasts or peroxisomes. In general, oxidative damage to proteins was more
      intense in the cultivar with the lower content of ascorbic acid, particularly in
      the chloroplast stroma. Water stress caused a marked increase in oxidative damage
      to proteins, particularly in mitochondria and peroxisomes. These results indicate
      that mitochondria are the main target for oxidative damage to proteins under well
      irrigated and drought conditions.

PMID- 15258168
TI  - O-acetylserine (thiol) lyase: an enigmatic enzyme of plant cysteine biosynthesis
      revisited in Arabidopsis thaliana.
AB  - The synthesis of cysteine is positioned at a decisive stage of assimilatory
      sulphate reduction, marking the fixation of inorganic sulphide into a carbon
      skeleton. O-acetylserine (thiol) lyase (OAS-TL) catalyses the reaction of
      inorganic sulphide with O-acetylserine (OAS). Despite its prominent position in
      the pathway OAS-TL is generally regarded as a non-limiting enzyme without
      regulatory function, due to low substrate affinities and semi-constitutive
      expression patterns. To resolve this apparent contradiction, the kinetic
      properties of three OAS-TLs from Arabidopsis thaliana, localized in the cytosol
      (A), plastids (B), and mitochondria (C), were analysed. The recombinant expressed
      OAS-TLs were purified to apparent homogeneity without any fusion tag to maintain
      their native forms. The proteins displayed high specific activities of 550-900
      micromol min(-1) mg(-1). Using an improved and highly sensitive assay method for
      cysteine determination, the apparent K(m)(sulphide) was 3-6 microM for OAS-TL A,
      B, and C and thus 10-100 times lower than previously reported for plant OAS-TLs.
      K(m)(OAS) was between 310 microM and 690 microM for OAS-TL isoform A, B, and C,
      whereas the apparent dissociation binding constant for OAS was much lower (K(d)<1
      microM OAS). A HPLC method was developed for OAS quantification that revealed
      fast increases of the cellular OAS concentration in response to sulphate
      deprivation. The observed fluctuations of intracellular OAS concentrations,
      combined with the OAS dissociation constant and the catalytic properties of OAS
      TL, support the model of a dynamic cysteine synthesis system with regulatory
      function as can be expected from the position of the reaction in the sulphur
      assimilation pathway.

PMID- 15258169
TI  - Plant sulphate transporters: co-ordination of uptake, intracellular and long
      distance transport.
AB  - Proton/sulphate co-transport in the plasma membrane of root cells is the first
      step for the uptake of sulphate from the environment by plants. Further
      intracellular, cell-to-cell and long-distance transport must fulfil the
      requirements for sulphate assimilation and source/sink demands within the plant.
      A gene family of sulphate transporters, which may be subdivided into five groups,
      has been identified with examples from many different plant species. For at least
      two groups, proton/sulphate co-transport activity has been confirmed. It appears
      that each group represents sulphate transporters with distinct kinetic
      properties, patterns of expression, and cell/tissue specificity related to
      specific roles in the uptake and allocation of sulphate. High-affinity sulphate
      uptake and low-affinity vascular transport, as well as vacuolar efflux, are
      controlled by the nutritional status of the plant. Most notably there is an
      apparent increase in capacity for cellular sulphate uptake and vacuolar efflux
      when sulphur supply is limiting. Within the groups, the individual sulphate
      transporters may be further subdivided by differences in temporal, cellular and
      tissue expression. Many of the transporters are regulated by the nutritional
      status of the individual tissues, to optimize sulphate movement within and
      between sink and source organs.

PMID- 15258170
TI  - A genetic map of candidate genes and QTLs involved in tomato fruit size and
      composition.
AB  - In order to screen for putative candidate genes linked to tomato fruit weight and
      to sugar or acid content, genes and QTLs involved in fruit size and composition
      were mapped. Genes were selected among EST clones in the TIGR tomato EST database
      (http://www.tigr.org/tdb/tgi/lgi/) or corresponded to genes preferentially
      expressed in the early stages of fruit development. These clones were located on
      the tomato map using a population of introgression lines (ILs) having one segment
      of Lycopersicon pennellii (LA716) in a L. esculentum (M82) background. The 75 ILs
      allowed the genome to be segmented into 107 bins. Sixty-three genes involved in
      carbon metabolism revealed 79 loci. They represented enzymes involved in the
      Calvin cycle, glycolysis, the TCA cycle, sugar and starch metabolism, transport,
      and a few other functions. In addition, seven cell-cycle-specific genes mapped
      into nine loci. Fourteen genes, primarily expressed during the cell division
      stage, and 23 genes primarily expressed during the cell expansion stage, revealed
      24 and 26 loci, respectively. The fruit weight, sugars, and organic acids content
      of each IL was measured and several QTLs controlling these traits were mapped.
      Comparison between map location of QTLs and candidate gene loci indicated a few
      candidate genes that may influence the variation of sugar or acid contents.
      Furthermore, the gene/QTL locations could be compared with the loci mapped in
      other tomato populations.

PMID- 15258171
TI  - Activation of the Oryza sativa non-symbiotic haemoglobin-2 promoter by the
      cytokinin-regulated transcription factor, ARR1.
AB  - Using in silico methods, several putative phytohormone-responsive cis-elements in
      the Oryza sativa non-symbiotic haemoglobin (NSHB) 1-4 and Arabidopsis thaliana
      NSHB1-2 promoters have been identified. An OsNSHB2 promoter::GUS reporter gene
      fusion shows tissue-specific expression in A. thaliana. GUS expression was
      observed in roots, the vasculature of young leaves, in flowers, and in the
      pedicel/stem junction. In transient assays, activity of the OsNSHB2 promoter was
      significantly up-regulated in the presence of the cytokinin, 6-benzylaminopurine
      (BA). Deletion analyses indicated that the full-length promoter was required for
      maximal trans-activation in the presence of cytokinin. Mutation of the single
      cytokinin-regulated ARR1-binding element abolished promoter activation in
      response to cytokinin. Constitutive expression of ARR1 under the control of the
      35S cauliflower mosaic virus promoter enhanced wild-type OsNSHB2 promoter
      activity, but had no effect on the activity of the mutated promoter in the
      absence of cytokinin. However, overexpression of ARR1 in the presence of
      cytokinin resulted in super-activation of the wild-type promoter. The mutated
      promoter was only moderately activated in the presence of cytokinin and ARR1,
      indicating that the OsNSHB2 promoter can be regulated by the ARR1 protein, but
      requires other cytokinin-induced factors for optimal activation. This is the
      first report that identifies a trans-acting factor involved in the activation of
      a NSHB gene.

PMID- 15258172
TI  - Bioinformatics as a critical prerequisite to transcriptome and proteome studies.
AB  - Large-scale genomic studies rely strongly on annotations available in databases
      to design experimental supports such as arrays or to explain results in term of
      biological meaning. Most of this information originates from bioinformatic
      predictions. Their accuracy as well as their relevance to existing biological
      data are critical in avoiding the misinterpretation of experimental results.

PMID- 15258173
TI  - Symbolic plant(s) of the Olympic Games.
AB  - The victors of the Olympic Games in ancient Greece were awarded crowns made of
      olive branches. In Antiquity, the symbolism of plants was related to myths,
      properties, aesthetic values, and civilization. Theophrastus first classifies and
      identifies plants, and gathers information about them, in his classic books (4th
      century BC). Symbolic plants are native to the Mediterranean region and they
      exhibit some convergent behaviour with respect to their functional
      characteristics. These plants were collected (among other species) by Professor
      J. Sibthorp and his partners in two botanical journeys in the Levant during the
      18th century, and they have been illustrated for Flora Graeca Sibthorpiana.

PMID- 15258174
TI  - A rapid method for assessing the distribution of gold labeling on thin sections.
AB  - Particulate gold labeling on ultrathin sections is in widespread use for antigen
      localization at the EM level. To extend the usefulness of gold labeling
      technology, we are evaluating different methods for sampling and estimating
      quantities of gold labeling. Here we present a simple, rapid, and unbiased method
      for assessing the relative pool sizes of immunogold labeling distributed over
      different cell compartments. The method uses a sampling approach developed for
      stereology in which a regular array of microscopic fields or linear scans is
      positioned randomly on labeled sections. From these readouts, gold particles are
      counted and assigned to identifiable cell structures to construct a gold labeling
      frequency distribution of those labeled compartments. Here we use ultrathin
      cryosections labeled for a range of different proteins and for a signaling lipid.
      We show by scanning labeled sections at the electron microscope that counting 100
      200 particles on each of two grids is sufficient to obtain a reproducible and
      rapid assessment of the pattern of labeling proportions over 10-16 compartments.
      If more precise estimates of labeling proportions over individual compartments
      are required (e.g., to achieve coefficients of error of 10-20%), then 100-200
      particles need to be counted over each compartment of interest.

PMID- 15258175
TI  - Detection of nascent and/or mature forms of oviductin in the female reproductive
      tract and post-ovulatory oocytes by use of a polyclonal antibody against
      recombinant hamster oviductin.
AB  - Oviductins belong to a family of glycoproteins that have been suggested to play
      several roles during the early processes of reproduction. Recently, a polyclonal
      antibody was raised against recombinant hamster oviductin (rhaOv(m)). Here the
      anti-rhaOv(m) antibody was used to investigate the sites of localization of
      oviductin in the female golden hamster. In the hamster oviduct, immunolabeling
      was restricted to the content of the Golgi saccules and secretory granules of the
      non-ciliated oviduct cells. After its release into the lumen, oviductin becomes
      associated with the zona pellucida of post-ovulatory oocytes. In unfertilized
      oocytes, oviductin was also detected in membrane invaginations along the oolemma
      and in some vesicles within the ooplasm. Furthermore, oviductin was detected over
      the microvilli and within multivesicular bodies of uterine epithelial cells.
      Western blotting analysis revealed the presence of oviductin in the hamster
      oviduct but not in the uterus or ovary. In the oviduct, the anti-rhaOv(m)
      antibody detected a polydispersed band corresponding to native oviductin (160-350
      kD) and several lower molecular weight bands (<100 kD) corresponding to nascent
      and partially glycosylated forms of oviductin. The anti-rhaOv(m) antibody
      provides an additional tool for investigation into the cytochemical and
      biochemical properties of different forms of hamster oviductin in the female
      reproductive tract.

PMID- 15258176
TI  - Rapid analysis of mitochondrial DNA depletion by fluorescence in situ
      hybridization and immunocytochemistry: potential strategies for HIV therapeutic
      monitoring.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) have been a mainstay in the
      treatment of human immunodeficiency virus since the introduction of
      azidothymidine (AZT) in 1987. However, none of the current therapies can
      completely eradicate the virus, necessitating long-term use of anti-retroviral
      drugs to prevent viral re-growth. One of the side effects associated with long
      term use of NRTIs is mitochondrial toxicity stemming from inhibition of the
      mitochondrial DNA (mtDNA) polymerase gamma, which leads to mtDNA depletion and
      consequently to mitochondrial dysfunction. Here we report the use of fluorescence
      in situ hybridization (FISH) and immunocytochemistry (ICC) to monitor mtDNA
      depletion in cultured fibroblasts treated with the NRTI 2',3'-dideoxycytidine
      (ddC). These techniques are amenable to both microscopy and flow cytometry,
      allowing analysis of populations of cells on a single-cell basis. We show that,
      as mtDNA depletion progresses, a mosaic population develops, with some cells
      being depleted of and others retaining mtDNA. These techniques could be useful as
      potential therapeutic monitors to indicate when NRTI therapy should be
      interrupted to prevent mitochondrial toxicity and could aid in the development of
      less toxic NRTIs by providing an assay suitable for pharmacodynamic evaluation of
      candidate molecules.

PMID- 15258177
TI  - Vascular mural cells in healing canine myocardial infarcts.
AB  - Angiogenesis is a critical process in healing of myocardial infarcts, leading to
      the formation of highly vascular granulation tissue. However, effective cardiac
      repair depends on mechanisms that inhibit the angiogenic process after a mature
      scar is formed, preventing inappropriate expansion of the fibrotic process. Using
      a canine model of reperfused myocardial infarction, we demonstrated that
      maturation of the infarct leads to the formation of neovessels, with a thick
      muscular coat, that demonstrate distinct morphological characteristics. Many of
      these "neoarterioles" lack a defined internal elastic lamina and demonstrate
      irregular deposits of extracellular matrix in the media. Vascular mural cells in
      healing infarcts undergo phenotypic changes, showing minimal expression of desmin
      during the proliferative phase (1 hr occlusion/7 days reperfusion) but in the
      mature scar (8 weeks reperfusion) acquire a phenotype similar to that of vascular
      smooth muscle cells in control areas. Non-muscle myosin heavy chains A and B are
      induced in infarct endothelial cells and myofibroblasts, respectively, but are
      not expressed in neovascular mural cells. Recruitment of a muscular coat and
      formation of neoarterioles in mature scars may inhibit endothelial cell
      proliferation and vascular sprouting, stabilizing the infarct vasculature.

PMID- 15258178
TI  - Differential expression of apolipoprotein d in human astroglial and
      oligodendroglial cells.
AB  - Apolipoprotein D (Apo D) is a secreted lipocalin in the nervous system that may
      be related to processes of reinnervation and regeneration. Under normal
      conditions, Apo D is present in the central nervous system in oligodendrocytes,
      astrocytes, and some scattered neurons. To elucidate the regional and cellular
      distribution of Apo D in normal human brain, we performed double
      immunohistochemistry for glial fibrillary acidic protein (GFAP) and Apo D in
      samples of postmortem human cerebral and cerebellar cortices. Most of the GFAP
      positive cells in the gray matter had features of protoplasmic astrocytes and
      were mainly Apo D-positive. Apo D staining was mostly confined to the cell soma
      and proximal processes, whereas GFAP extended to a rich and extensive array of
      processes. The fibrous astrocytes in the white matter were immunoreactive for
      GFAP but not for Apo D. In the white matter, Apo D was mainly detected in
      oligodendrocytes and extracellularly in the neuropil. The results of the present
      study support a specific behavior for each astrocyte type. These findings suggest
      that Apo D expression may be cell-specific, depending on the particular tissue
      physiology at the time of examination.

PMID- 15258179
TI  - Tight junction proteins ZO-1, occludin, and claudins in developing and adult
      human perineurium.
AB  - In peripheral nerves, groups of Schwann cell-axon units are isolated from the
      adjacent tissues by the perineurium, which creates a diffusion barrier
      responsible for the maintenance of endoneurial homeostasis. The perineurium is
      formed by concentric layers of overlapping, polygonal perineurial cells that form
      tight junctions at their interdigitating cell borders. In this study, employing
      indirect immunofluorescence and immunoelectron microscopy, we demonstrate that
      claudin-1 and -3, ZO-1, and occludin, but not claudin-2, -4, and -5, are
      expressed in the perineurium of adult human peripheral nerve. We also describe
      the expression of occludin, ZO-1, claudin-1, -3, and -5 in the developing human
      perineurium, showing that the expressions of claudin-1 and -3, ZO-1, and occludin
      follow similar spatial developmental expression patterns but follow different
      timetables in achieving their respective adult distributions. Specifically,
      claudin-1 is already largely restricted to perineurium-derived structures at 11
      fetal weeks, whereas claudin-3 and occludin are weakly expressed in the
      perineurial structures at this age and acquire a well-defined perineurial
      distribution only between 22 and 35 fetal weeks. ZO-1 appears to acquire its
      mature profile even later during the third trimester. The results of the present
      and previous studies show that the perineurial diffusion barrier matures
      relatively late during human peripheral nerve development.

PMID- 15258180
TI  - Destiny and intracellular survival of Leishmania amazonensis in control and
      dexamethasone-treated glial cultures: protozoa-specific glycoconjugate tagging
      and TUNEL staining.
AB  - Leishmania amazonensis, an obligatory intracellular parasite, survives
      internalization by macrophages, but no information is available on the
      involvement of microglia. We have investigated microglia-protozoa interactions in
      mixed glial cultures infected with promastigote forms of L. amazonensis after
      lipopolysaccharide (LPS) or dexamethasone (DM) treatment. After 2 hr of exposure
      to parasites in control cultures, there was a small number of infected microglia
      (1%). Preincubation with LPS or DM led to 14% or 60% of microglial cells with
      attached parasites, respectively. DM treatment resulted in 39% of microglial
      cells with internalized parasites (controls or LPS-treated cells had < or =1%).
      Scanning electron micrographs showed numerous filopodia in DM-treated cells,
      whereas these projections were rarely observed in LPS-treated or control cells.
      DM treatment also affected the intramicroglial survival of Leishmania. In control
      cultures, internalized parasites, tagged with an anti-lipophosphoglycan (anti
      LPG) antibody, showed fragmented DNA [terminal deoxyribonucleotide transferase
      mediated dUTP-X nick end labeling (TUNEL+)] after 4 hr of interaction, but
      changes seemed slightly delayed in DM-treated cultures. After 12 hr, there were
      no LPG+/TUNEL+ profiles in controls, whereas rare LPG+ profiles still persisted
      in DM-treated cells. Our results suggest that microglia are highly effective in
      the elimination of Leishmania and that the process can be effectively studied by
      LPG/TUNEL double labeling.

PMID- 15258181
TI  - Carbonic anhydrase VI in the mouse nasal gland.
AB  - Western blotting analysis of mouse nasal tissue using a specific anti-mouse
      secreted carbonic anhydrase (CA VI) antibody has shown that CA VI is present in
      this tissue. A single immunoreactive band of 42 kD was observed, as has been
      found previously for salivary tissues. RT-PCR analysis has shown that nasal
      mucosa expressed CA VI mRNA. By immunohistochemistry (IHC), CA VI was observed in
      acinar cells, in duct contents of the anterior gland of the nasal septum, and in
      the lateral nasal gland. The Bowman's gland, the posterior gland of the nasal
      septum, and the maxillary sinus gland were negative. Immunoreactivity was also
      observed in the mucus covering the respiratory and olfactory mucosa and in the
      lumen of the nasolacrimal duct. In contrast, an anti-rat CA II antibody (that
      crossreacts with the mouse enzyme) stained only known CA II-positive cells and an
      occasional olfactory receptor neuron. These results indicate that CA VI is
      produced by the nasal gland and is secreted over the nasal mucosa. By reversible
      hydration of CO(2), CA VI is presumed to play a role in mucosal functions such as
      CO(2) sensation and acid-base balance. It may also play a role in olfactory
      function as a growth factor in maturation of the olfactory epithelial cells.

PMID- 15258182
TI  - Immunohistochemical identification of an extracellular matrix scaffold that
      microguides capillary sprouting in vivo.
AB  - To gain insight into how a naturally occurring scaffold composed of extracellular
      matrix (ECM) proteins provides directional guidance for capillary sprouting, we
      examined angiogenesis in whole-mount specimens of rat mesentery. Angiogenesis was
      studied in response to normal maturation, the injection of a mast cell
      degranulating substance (compound 48/80), and mild wounding. Confocal microscopy
      of specimens immunolabeled for elastin revealed a network of crosslinked elastic
      fibers with a density of 140.8 +/- 37 mm of fiber/mm(2) tissue. Fiber diameters
      ranged from 180 to 1400 nm, with a mean value of 710 +/- 330 nm. Capillary
      sprouts contained CD31- and OX-43-positive endothelial cells as well as desmin
      positive pericytes. During normal maturation, leading endothelial cells and
      pericytes were in contact and aligned with an elastic fiber in approximately 80
      90% of all sprouts. In wounding and compound 48/80-treated specimens, in which
      angiogenesis was markedly increased, leading endothelial cells remained in
      contact and aligned with elastic fibers in approximately 60-80% of all sprouts.
      These observations indicate that elastic fibers are used for endothelial and
      pericyte migration during capillary sprouting in rat mesentery. The composition
      of this elastic fiber matrix may provide important clues for the development of
      tissue-engineered scaffolds that support and directionally guide angiogenesis.

PMID- 15258183
TI  - Differential expression of basement membrane components in lymphatic tissues.
AB  - Peripheral lymphoid tissues act as important organs of immunological defense.
      Characteristic of their architecture is the rich reticular fiber meshwork
      composed of various extracellular matrix (ECM) molecules with which the
      stationary non-lymphatic cells stay in intimate contact and form channels through
      which the lymphatic cells travel. Here we studied the distribution of various
      laminin (Ln) chains and different types of collagens in human spleen, lymph node,
      and tonsil to clarify their chain-specific distribution. The most widely
      distributed proteins in all these organs were Ln chains alpha5, beta1, gamma1 and
      collagen types IV and XVIII, which were present in practically all compartments.
      Conversely, Ln alpha1, alpha2, alpha4, and type VII collagen showed a more
      restricted expression pattern. A unique feature was that Ln alpha3-, beta3-, and
      gamma2-chains, which normally are not localized to the vascular wall in non
      lymphatic tissues, were present also in capillary basement membranes (BMs) of the
      follicular structures of lymph node and tonsil and in Ln alpha1-chain and type
      VII collagen also in the splenic white pulp. We also found that collagen XVII was
      exclusively present in the ring fibers of the spleen. The results indicate that
      BMs of lymphatic tissues contain a variety of macromolecules that probably
      contribute strongly to immunological events. In addition, capillaries of the
      lymphoid tissue exhibit a specified BM composition resembling that in epithelial
      BMs of non-lymphoid tissues.

PMID- 15258184
TI  - Differential expression of CD44 during human prostate epithelial cell
      differentiation.
AB  - CD44 is a polymorphic transmembrane glycoprotein that binds hyaluronan and growth
      factors. Multiple isoforms of the protein can be generated by alternative
      splicing but little is known about the expression and function of these isoforms
      in normal development and differentiation. We have investigated the expression of
      CD44 during normal prostate epithelial cell differentiation. A conditionally
      immortalized prostate epithelial cell line, Pre2.8, was used as a model system.
      These cells proliferate at 33C but at 39C stop dividing and undergo changes
      consistent with early stages of cell differentiation. During the differentiation
      of these cells, the expression of the CD44 isoform v3-v10 was upregulated. Two
      layers of epithelial cells can clearly be distinguished in the human prostate, a
      basal layer expressing keratins 5/14 and a luminal layer expressing keratins
      8/18. In prostate tissue the v3-v10 isoform was found predominantly in basal
      cells but also in keratin 14-negative, keratin 19-positive cells intermediate
      between the two layers. CD44 v3-v10 was also expressed in other keratin 14
      negative prostate tissues, the ejaculatory ducts and prostatic urethra.
      Therefore, CD44 v3-v10 may be important as a cell surface marker for
      differentiating cells in the prostate epithelium.

PMID- 15258185
TI  - Attenuation of neointimal vascular smooth muscle cellularity in atheroma by
      plasminogen activator inhibitor type 1 (PAI-1).
AB  - Rupture of vulnerable atheroma often underlies acute coronary syndromes.
      Vulnerable plaques exhibit a paucity of vascular smooth muscle cells (VSMCs) in
      the cap. Therefore, decreased VSMC migration into the neointima may predispose to
      vulnerability. The balance between cell surface plasminogen activator activity
      and its inhibition [mediated primarily by plasminogen activator inhibitor type 1
      (PAI-1)] modulates migration of diverse types of cells. We sought to determine
      whether increased expression of PAI-1 would decrease migration of VSMCs in vitro
      and neointimal cellularity in vivo in apolipoprotein E knockout (ApoE(-/-)) mice
      fed a high-fat diet. Increased vessel wall expression of PAI-1 in transgenic mice
      was induced with the SM22alpha promoter. VSMC migration through Matrigel in vitro
      was quantified with laser scanning cytometry. Expression of PAI-1 was increased
      threefold in the aortic wall of SM22-PAI transgene-positive mice. Neointimal
      cellularity of vascular lesions was decreased by 26% (p=0.01; n=5 each) in ApoE(
      /-) mice with the SM22-PAI transgene compared with ApoE(-/-) mice. VSMCs
      explanted from transgene-positive mice exhibited twofold greater expression of
      PAI-1 and their migration was attenuated by 27% (p=0.03). Accordingly, increased
      expression of PAI-1 protein by VSMCs reduces their migration in vitro and their
      contribution to neointimal cellularity in vivo.

PMID- 15258186
TI  - Carbonic anhydrase in mammalian vascular smooth muscle.
AB  - Carbonic anhydrase (CA) is ubiquitously expressed and plays a pivotal role in
      acid-base balance, ion transport, and gas exchange. Limited observations by
      others, derived from functional, pharmacological, and histochemical studies,
      suggest that CA is present in vascular smooth muscle and is involved in
      vasoregulation. The present study, using measurements of bioactivity, inhibition
      characteristics, and immunohistochemical analysis, was undertaken to more fully
      evaluate CA in vascular smooth muscle. In isolated bovine aortic smooth muscle,
      which is devoid of erythrocytes, CA is present in low concentrations with a CO(2)
      hydration activity (at 0C) of 3.5 +/- 2.7 U/g. The I(50) for acetazolamide
      inhibition is 0.07 +/- 0.01 microM. Results with dorzolamide and bromopyruvate,
      selective inhibitors of the CA II and I isozymes, respectively, show that roughly
      75% of the CA activity is accounted for by CA I, with 20% due to CA II. These
      results accord qualitatively with immunocytochemical staining with specific CA I
      and II antibodies, showing that both isozymes are present and that their staining
      co-localizes with cells positive for smooth muscle alpha-actin. These data
      establish the activity, inhibition, and isozyme pattern of carbonic anhydrase
      expression in mammalian vascular smooth muscle.

PMID- 15258187
TI  - Immunohistochemical demonstration of carbonic anhydrase isoenzyme VI (CA VI)
      expression in rat lower airways and lung.
AB  - Carbonic anhydrase isoenzyme VI (CA VI), which is transported in high
      concentrations in saliva and milk into the alimentary tract, is an important
      element of mucosal protection in the upper alimentary tract. Like alimentary
      tract mucosa, the respiratory tract mucosa is also exposed to heavy microbial,
      physical, and chemical stress. The protective and renewal-promoting factors
      present in the surface mucus of the respiratory tract are mainly produced by the
      seromucous tracheobronchial glands. Here we studied the secretion of CA VI by
      these glands in adult and developing rats using immunohistochemical techniques.
      The serous acinar and duct cells of the tracheobronchial glands stained for CA
      VI. The presence of the enzyme also in the duct content indicates its active
      secretion into the surface mucus. CA VI was also visible in the secretory cells
      and at the base of the ciliated cells of the tracheobronchial surface epithelium.
      Moreover, the Clara cells of the bronchiolar surface epithelium stained for CA
      VI. These findings are consistent with the hypothesis that CA VI has a mucosa
      protective role not only in the gastrointestinal tract but also in the
      respiratory tract, where CA VI may act as a pivotal pH neutralizer and growth
      factor.

PMID- 15258188
TI  - Fluorescence in situ hybridization analysis reveals multiple loci of knob
      associated DNA elements in one-knob and knobless maize lines.
AB  - Fluorescence in situ hybridization analyses were conducted to examine the
      presence or absence of the 180- and 350-bp knob-associated tandem repeats in
      maize strains previously defined as "one-knob" or "knobless." Multiple loci were
      found to hybridize to these two repeats in all maize lines analyzed. Our results
      show that the number of 180- and 350-bp repeat loci do not correlate with the
      number of knobs in maize and that these tandem repeats are not independently
      sufficient to confer knob heterochromatin, even when present at megabase sizes.

PMID- 15258189
TI  - R5 HIV gp120-mediated cellular contacts induce the death of single CCR5
      expressing CD4 T cells by a gp41-dependent mechanism.
AB  - The use of CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5) by
      X4 and R5 human immunodeficiency virus (HIV) envelopes (Env) influences HIV
      cytopathicity. Here, we have evaluated the role of CCR5 and gp41 in Env-induced
      cell death occurring during the contacts of uninfected, primary cells with MOLT
      cells infected with different R5 and X4 HIV isolates. As reported for X4-Env, R5
      HIV-infected cells destroyed CD4 T cells expressing the appropriate coreceptor by
      inducing the formation of syncytia and the death of single target cells.
      Therefore, only the small (<10%) CCR5+ subset of primary CD4 T cells was
      sensitive to cellular presentation of R5-Env, and CCR5-CD4 T cells showed
      complete resistance to R5-Env-mediated cell death. X4- and R5-infected cells
      killed single primary cells by a common mechanism that was dependent on gp41
      function and induced a rapid loss of mitochondrial membrane potential and plasma
      membrane integrity in target cells. Single-cell death was not affected by the
      blockade of HIV replication in target cells or G-protein signaling through
      CXCR4/CCR5. In contrast, caspase inhibition (Z-Val-Ala-Asp-fluoromethylketone)
      profoundly changed the outcome of cell-to-cell contacts by reducing the number of
      single dead CD4 T cells and increasing the rate of syncytium formation. In
      conclusion, X4 and R5 HIV Env share a common gp41-dependent mechanism to kill CD4
      T cells during cellular contacts. Env tropism and coreceptor expression but not
      differential killing mechanisms seem to govern the extent of cytopathic effects
      induced by HIV infection.

PMID- 15258190
TI  - The THC-induced suppression of Th1 polarization in response to Legionella
      pneumophila infection is not mediated by increases in corticosterone and PGE2.
AB  - T helper cell type 1 (Th1)-polarizing cytokines are induced by Legionella
      pneumophila infection and are suppressed by pretreatment with marijuana
      cannabinoids (CB). Glucocorticoids and prostaglandin E2(PGE2) are also reported
      to suppress Th1 polarization and are induced by Delta9-tetrahydrocannabinol
      (THC), so their role in the suppression of polarizing cytokines was examined.
      Injection of L. pneumophila or THC alone into BALB/c mice induced a rapid and
      transient rise in serum corticosterone (CS), and the injection of both agents
      significantly augmented the CS response, demonstrating that THC increased CS in
      Legionella-infected mice. Pretreatment with the CB receptor 1 (CB1) antagonist
      SR141716A had no effect on the THC-induced CS response, but CB2 antagonist
      (SR144528) treatment increased the CS response. To see if increased CS
      contributed to the down-regulation of Th1 cytokines, mice were pretreated with
      the steroid antagonist RU486 before THC injection and Legionella infection. The
      results showed that RU486 did not attenuate the THC-induced suppression of serum
      interleukin (IL)-12 or interferon-gamma (IFN-gamma). In addition to CS, THC
      injection increased urinary PGE2 metabolites, and the CB1 antagonist attenuated
      this increase. Although L. pneumophila infection increased urinary PGE2, THC
      pretreatment did not enhance this response; in addition, treatment with the
      cyclooxygenase inhibitor, indomethacin, did not block the THC-induced suppression
      of IL-12 and IFN-gamma. These results suggest that the elevation of CS and PGE2
      does not account for the THC-induced attenuation of the Th1 cytokine response,
      and it is concluded that other suppressive mediators are induced by THC or that
      the drug acts directly on immune cells to suppress cytokine production.

PMID- 15258191
TI  - Prolonged Toll-like receptor stimulation leads to down-regulation of IRAK-4
      protein.
AB  - Interleukin-1 receptor-associated kinase (IRAK)-4 is a key mediator in the Toll
      like receptor (TLR) signaling. We found that stimulation of TLR2, TLR4, or TLR9,
      but not TLR3, caused a decrease in IRAK-4 protein without affecting its mRNA
      level in a mouse macrophage cell line, RAW 264. The decrease in IRAK-4 was
      accompanied by the appearance of a smaller molecular weight protein (32 kD),
      which was recognized by an anti-IRAK-4 antibody raised against the C-terminal
      region. The decrease in IRAK-4 and the appearance of the 32-kD protein occurred
      with slower kinetics than the activation of IRAK-1 and were suppressed by
      inhibitors of the proteasome, inducible inhibitor of kappaBalpha phosphorylation
      or protein synthesis, but not by caspase inhibitors. These results indicate that
      prolonged stimulation of TLR2, TLR4, or TLR9 causes a down-regulation of IRAK-4
      protein, which may be mediated through cleavage of IRAK-4 by a protease induced
      by the activation of nuclear factor-kappaB.

PMID- 15258192
TI  - Counteracting corneal immunoinflammatory lesion with interleukin-1 receptor
      antagonist protein.
AB  - Herpetic stromal keratitis (HSK) is a T cell-orchestrated, immunoinflammatory
      lesion that results from corneal Herpes simplex virus infection. Previous reports
      indicate an essential role for proinflammatory cytokine interleukin (IL)-1 in HSK
      pathogenesis. The present study evaluates the efficacy of IL-1 receptor
      antagonist (IL-1 ra) protein in the management of HSK. Mice receiving IL-1 ra had
      diminished disease severity. The administration of IL-1 ra was shown to reduce
      the influx into the cornea of cells of the innate and adaptive immune response.
      In addition, the treatment diminished corneal vascular endothelial growth factor
      levels, resulting in reduced angiogenic response. Our results show the importance
      of targeting early proinflammatory molecules such as IL-1 to counteract HSK and
      advocate IL-1 ra as an effective agent to achieve this.

PMID- 15258193
TI  - Enzyme blockade: a nonradioactive method to determine the absolute rate of
      cholesterol synthesis in the brain.
AB  - The standard in vivo method to determine rates of brain cholesterol synthesis
      involves systemic injection of (3)H(2)O and measurement of incorporated
      radioactivity in sterols. Herein, we describe an alternative method ("enzyme
      blockade") that obviates the use of radioactivity. The method relies on the
      ability of AY9944, a potent and relatively selective inhibitor of cholesterol
      synthesis, to cause the time-dependent accumulation of 7-dehydrocholesterol
      (DHC), a cholesterol precursor detected with sensitivity and specificity by
      reverse-phase HPLC-coupled spectrophotometry at 282 nm. To validate the method,
      adult AY9944-treated and control mice were injected with [(3)H]acetate. After 24
      h, most of the radioactivity in brain sterols from treated mice accumulated in
      DHC, without significantly perturbing overall sterol pathway activity, compared
      with controls (where cholesterol was the dominant radiolabeled sterol, with no
      label found in DHC). When adult mice were treated continuously with AY9944, the
      time-dependent accumulation of DHC in brain was linear (after approximately 8 h)
      for 3 days. The rate of brain cholesterol synthesis determined by this method (
      approximately 30 microg/g/day) closely agrees with that determined by the
      radioactive method. We also determined the cholesterol synthesis rate in
      different regions of adult mouse brain, with frontal cortex having the highest
      rate and cerebellum having the lowest rate.

PMID- 15258194
TI  - Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells.
AB  - Niacin is a widely used lipid-regulating agent in dyslipidemic patients.
      Previously, we have shown that niacin inhibits triacylglycerol synthesis. In this
      report, using HepG2 cells, we have examined the effect of niacin on the mRNA
      expression and microsomal activity of diacylglycerol acyltransferase 1 and 2
      (DGAT1 and DGAT2), the last committed but distinctly different enzymes for
      triglyceride synthesis. Addition of niacin to the DGAT assay reaction mixture
      dose-dependently (0-3 mM) inhibited DGAT activity by 35-50%, and the IC(50) was
      found to be 0.1 mM. Enzyme kinetic studies showed apparent K(m) values of 8.3
      microM and 100 microM using [(14)C]oleoyl-CoA and sn-1,2-dioleoylglycerol as
      substrates, respectively. A decrease in apparent V(max) was observed with niacin,
      whereas the apparent K(m) remained constant. A Lineweaver-Burk plot of DGAT
      inhibition by niacin showed a noncompetitive type of inhibition. Niacin
      selectively inhibited DGAT2 but not DGAT1 activity. Niacin inhibited overt DGAT
      activity. Niacin had no effect on the expression of DGAT1 and DGAT2 mRNA. These
      data suggest that niacin directly and noncompetitively inhibits DGAT2 but not
      DGAT1, resulting in decreased triglyceride synthesis and hepatic atherogenic
      lipoprotein secretion, thus indicating a major target site for its mechanism of
      action.

PMID- 15258195
TI  - Atherosclerosis in perlecan heterozygous mice.
AB  - The hypothesis that lipoprotein association with perlecan is atherogenic was
      tested by studying atherosclerosis in mice that had a heterozygous deletion of
      perlecan, the primary extracellular heparan sulfate proteoglycan in arteries. We
      first studied the expression of perlecan in mouse lesions and noted that this
      proteoglycan in aorta was found in the subendothelial matrix. Perlecan was also a
      major component of the lesional extracellular matrix. Mice with a heterozygous
      deletion had a reduction in arterial wall perlecan expression. Atherosclerosis in
      these mice was studied after crossing the defect into the apolipoprotein E (apoE)
      and LDL receptor knockout backgrounds. At 12 weeks, chow-fed apoE null mice with
      a heterozygous deletion had less atherosclerosis. However, at 24 weeks and in the
      LDL receptor heterozygous background, the presence of a perlecan knockout allele
      did not significantly alter lesion size. Thus, it appears that loss of perlecan
      leads to less atherosclerosis in early lesions. Although this might be
      attributable to a decrease in lipoprotein retention, it should be noted that
      perlecan might mediate multiple other processes that could, in sum, accelerate
      atherosclerosis.

PMID- 15258196
TI  - PLTP deficiency improves the anti-inflammatory properties of HDL and reduces the
      ability of LDL to induce monocyte chemotactic activity.
AB  - We reported that phospholipid transfer protein (PLTP) deficiency decreased
      atherosclerosis in mouse models. Because the decreased atherosclerosis was
      accompanied by a significant decrease in plasma HDL levels, we examined the
      properties of PLTP knockout (PLTP0) HDL and tested its ability to prevent LDL
      induced monocyte chemotactic activity in human artery wall cell cocultures. We
      isolated HDL and LDL from LDL receptor knockout/PLTP knockout (LDLr0/PLTP0) mice
      and from apolipoprotein B transgenic (apoBTg)/PLTP0 mice as well as their
      controls. PLTP0 HDL was relatively rich in protein and depleted in
      phosphatidylcholine. Turnover studies revealed a 3.5- to 4.0-fold increase in the
      turnover of protein and cholesteryl ester in HDL from PLTP0 mice compared with
      control mice. The ability of HDL from LDLr0/PLTP0 and apoBTg/PLTP0 mice to
      prevent the induction of monocyte chemotactic activity in human artery wall cell
      cocultures exposed to human LDL was dramatically better than that in controls.
      Moreover, LDL from PLTP0 mice was markedly resistant to oxidation and induced
      significantly less monocyte chemotactic activity compared with that in controls.
      In vitro, PLTP0 HDL removed significantly more oxidized phospholipids from LDL
      than did control HDL. We conclude that PLTP deficiency improves the anti
      inflammatory properties of HDL in mice and reduces the ability of LDL to induce
      monocyte chemotactic activity.

PMID- 15258197
TI  - Definition of the immunogenic forms of modified human LDL recognized by human
      autoantibodies and by rabbit hyperimmune antibodies.
AB  - Humans and laboratory animals recognize human modified LDL as immunogenic. Immune
      complexes (ICs) isolated from human sera contain malondialdehyde-modified LDL
      (MDA-LDL) and N (epsilon)(carboxymethyl)lysine-modified LDL (CML-LDL) as well as
      antibodies reacting with MDA-LDL, copper-oxidized LDL (OxLDL), CML-LDL, and
      advanced glycosylation end product (AGE)-modified LDL. OxLDL and AGE-LDL
      antibodies isolated from human sera recognize the same LDL modifications and do
      not react with modified non-LDL proteins. Rabbit antibodies have different
      reactivity patterns: MDA-LDL antibodies react strongly with MDA-LDL and MDA-BSA
      but weakly with OxLDL; OxLDL antibodies react strongly with OxLDL and weakly with
      MDA-LDL; CML-LDL antibodies react with CML-LDL > CML-BSA > AGE-LDL > OxLDL; AGE
      LDL antibodies react strongly with AGE-LDL, react weakly with OxLDL, and do not
      react with CML-LDL. Thus, human and rabbit antibodies seem to recognize different
      epitopes. Capture assays carried out with all rabbit antibodies showed binding of
      apolipoprotein B-rich lipoproteins isolated from ICs, suggesting that laboratory
      generated epitopes are expressed by in vivo-modified LDL, although they are not
      necessarily recognized by the human immune system. Thus, the definition of
      immunogenic forms of modified LDL eliciting human autoimmune responses requires
      the isolation and characterization of autoantibodies and modified LDL from human
      samples, whereas rabbit antibodies can be used to detect in vivo-modified human
      LDL.

PMID- 15258198
TI  - Association of APOE genotype with carotid atherosclerosis in men and women: the
      Framingham Heart Study.
AB  - The aim of this study was to determine the association between APOE genotype and
      carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis,
      and to assess if other cardiovascular risk factors modify this association. A
      total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent
      carotid ultrasound during examination cycle 6 and had complete data on APOE
      genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2
      genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid
      IMT and the presence of carotid stenosis > 25% were determined by
      ultrasonography. In women, the APOE2 group was associated with lower carotid IMT
      (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95%
      confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE
      genotype was not associated with carotid IMT or stenosis in the whole group;
      however, diabetes modified the association between APOE genotype and carotid IMT
      (P for interaction = 0.044). Among men with diabetes, the APOE4 group was
      associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3
      group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with
      lower carotid atherosclerosis in women, and the E4 allele was associated with
      higher internal carotid IMT in diabetic men.

PMID- 15258199
TI  - Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells
      by PPARalpha-mediated redistribution of ABCB4.
AB  - Fibrates, including bezafibrate (BF), upregulate the expression of ATP binding
      cassette protein B4 (ABCB4) through gene transcription in mice. To determine the
      effects of BF on the expression levels of ABCB4 and on the stimulation of biliary
      phosphatidylcholine (PC) transport in human HepG2 hepatoblastoma cells, mRNA and
      protein levels as well as subcellular localization were investigated in the cells
      treated with BF. The canalicular accumulation of a fluorescent PC was assessed by
      confocal laser scanning microscopy. Treatment with 300 micromol/l BF for 24 h
      increased levels of ABCB4 mRNA but not protein by up to 151%. BF caused
      redistribution of ABCB4 into pseudocanaliculi formed between cells. In
      association with this redistribution, BF accelerated the accumulation of
      fluorescent PC in bile canaliculi (up to 163% of that in nontreated cells).
      Suppression of peroxisome proliferator-activated receptor alpha (PPARalpha)
      expression by either a small interfering RNA duplex or morpholino antisense
      oligonucleotide attenuated the BF-induced redistribution of ABCB4. These findings
      suggest that BF may enhance the capacity of human hepatocytes to direct PC into
      bile canaliculi via PPARalpha-mediated redistribution of ABCB4 to the canalicular
      membrane. This provides a rationale for the use of BF to improve cholestasis
      and/or cholangitis that is attributable to hypofunction of ABCB4.

PMID- 15258200
TI  - Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with
      dyslipidemia.
AB  - Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are
      the two most common familial dyslipidemias predisposing to premature coronary
      heart disease (CHD). These dyslipidemias share many phenotypic features,
      suggesting a partially overlapping molecular pathogenesis. This was supported by
      our previous pooled data analysis of the genome scans for low HDL-C and FCHL,
      which identified three shared chromosomal regions for a qualitative HDL-C trait
      on 8q23.1, 16q23.3, and 20q13.32. This study further investigates these regions
      as well as two other loci we identified earlier for premature CHD on 2q31 and
      Xq24 and a locus for high serum triglycerides (TGs) on 10q11. We analyzed 67
      microsatellite markers in an extended study sample of 1,109 individuals from 92
      low HDL-C or FCHL families using both qualitative and quantitative lipid
      phenotypes. These analyses provided evidence for linkage (a logarithm of odds
      score of 3.2) on 10q11 using a quantitative HDL-C trait. Importantly, this
      region, previously linked to TGs, body mass index, and obesity, provided evidence
      for association for quantitative TGs (P = 0.0006) and for a combined trait of HDL
      C and TGs (P = 0.008) with marker D10S546. Suggestive evidence for linkage also
      emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained
      for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL
      C and TGs.

PMID- 15258201
TI  - Are BMI and other anthropometric measures appropriate as indices for obesity? A
      study in an Asian population.
AB  - We have examined the relationships between percentage of body fat (PBF) and risk
      factors for cardiovascular disease and insulin resistance and how good body mass
      index (BMI) and other anthropometric measures are as indices of obesity. High PBF
      levels were associated with increased risk of cardiovascular disease and insulin
      resistance. The World Health Organization BMI of 30 kg/m(2) for obesity has low
      sensitivity, 6.7% and 13.4% for men and women, respectively. For every obese man
      and woman identified, 6.7 and 1.76 times nonobese men and women, respectively,
      will be misclassified as obese. With the locally established BMI cutoff point for
      obesity of 27 kg/m(2) for men and 25 kg/m(2) for women, the sensitivity was
      improved to 46.7% and 60.8%, respectively. For every obese man and woman
      identified, 3.76 and 1.64 times nonobese men and women, respectively, will be
      misclassified as obese. None of the other anthropometric indices was better than
      the locally established BMIs. We showed that the BMIs for obesity for our local
      men and women are different. These BMIs were most precise among all indices
      studied. However, they still lead to high false-positive rates. For more
      effective management of the problem of obesity, we need to develop more precise,
      simple, and cost-effective methods for the measurement of PBF.

PMID- 15258202
TI  - apoA-IV tagged with the ER retention signal KDEL perturbs the intracellular
      trafficking and secretion of apoB.
AB  - To examine the role of apolipoprotein A-IV (apoA-IV) in the intracellular
      trafficking and secretion of apoB, COS cells were cotransfected with microsomal
      triglyceride transfer protein (MTP), apoB-41 (amino terminal 41% of apoB), and
      either native apoA-IV or apoA-IV modified with the carboxy-terminal endoplasmic
      reticulum (ER) retention signal, KDEL (apoA-IV-KDEL). As expected, apoA-IV-KDEL
      was inefficiently secreted relative to native apoA-IV. Coexpression of apoB-41
      with apoA-IV-KDEL reduced the secretion of apoB-41 by approximately 80%. The apoA
      IV-KDEL effect was specific, as neither KDEL-modified forms of human serum
      albumin or apoA-I affected apoB-41 secretion. Similar results were observed in
      McA-RH7777 rat hepatoma cells, which express endogenous MTP. The full inhibitory
      effect of apoA-IV-KDEL on apoB secretion was observed only for forms of apoB
      containing a minimum of the amino-terminal 25% of the protein (apoB-25). However,
      apoA-IV-KDEL inhibited the secretion of both lipid-associated and lipid-poor
      forms of apoB-25. Dual-label immunofluorescence microscopy of cells transfected
      with native apoA-IV and apoB-25 revealed that both apolipoproteins were localized
      to the ER and Golgi, as expected. However, when apoA-IV-KDEL was cotransfected
      with apoB-25, both proteins localized primarily to the ER. These data suggest
      that apoA-IV may physically interact with apoB in the secretory pathway, perhaps
      reflecting a role in modulating the process of triglyceride-rich lipoprotein
      assembly and secretion.

PMID- 15258203
TI  - P-glycoprotein retains function when reconstituted into a sphingolipid- and
      cholesterol-rich environment.
AB  - P-glycoprotein (P-gp) appears to be associated within specialized raftlike
      membrane microdomains. The activity of P-gp is sensitive to its lipid
      environment, and a functional association in raft microdomains will require that
      P-gp retains activity in the microenvironment. Purified hamster P-gp was
      reconstituted in liposomes comprising sphingomyelin and cholesterol, both highly
      enriched in membrane microdomains and known to impart a liquid-ordered phase to
      bilayers. The activity of P-gp was compared with that of proteoliposomes composed
      of crude egg phosphatidylcholine (unsaturated) or dipalmitoyl phosphatidylcholine
      (saturated) in the presence or absence of cholesterol. The maximal rate of ATP
      hydrolysis was not significantly altered by the nature of the lipid species.
      However, the potencies of nicardipine and XR9576 to modulate the ATPase activity
      of P-gp were increased in the sphingolipid-based proteoliposomes. The drug-P-gp
      interaction was investigated by measurement of the rates of [(3)H]XR9576
      association and dissociation from the transporter. The lipid environment of P-gp
      did not affect these kinetic parameters of drug binding. In summary, P-gp retains
      function in liquid-ordered cholesterol and sphingolipid model membranes in which
      the communication between the transmembrane and the nucleotide binding domains
      after drug binding to the protein is more efficient.

PMID- 15258204
TI  - Cortical reorganisation in patients with MS.

PMID- 15258205
TI  - Recommended diagnostic criteria for paraneoplastic neurological syndromes.

PMID- 15258206
TI  - Misdiagnosis of seizures: insulinoma presenting as adult-onset seizure disorder.
AB  - Once diagnosed with a refractory seizure disorder, patients often receive
      aggressive and escalating pharmacotherapy. However, a significant proportion of
      patients referred to neurologists do not have epilepsy. Toxic and metabolic
      causes of seizures should always be considered as they are potentially curable,
      and may be fatal if untreated. The following case report highlights the need for
      careful reassessment of all seizures that are atypical and refractory to
      medication.

PMID- 15258207
TI  - Dietary niacin and the risk of incident Alzheimer's disease and of cognitive
      decline.
AB  - BACKGROUND: Dementia can be caused by severe niacin insufficiency, but it is
      unknown whether variation in intake of niacin in the usual diet is linked to
      neurodegenerative decline. We examined whether dietary intake of niacin was
      associated with incident Alzheimer's disease (AD) and cognitive decline in a
      large, prospective study. METHODS: This study was conducted in 1993-2002 in a
      geographically defined Chicago community of 6158 residents aged 65 years and
      older. Nutrient intake was determined by food frequency questionnaire. Four
      cognitive tests were administered to all study participants at 3 year intervals
      in a 6 year follow up. A total of 3718 participants had dietary data and at least
      two cognitive assessments for analyses of cognitive change over a median 5.5
      years. Clinical evaluations were performed on a stratified random sample of 815
      participants initially unaffected by AD, and 131 participants were diagnosed with
      4 year incident AD by standardised criteria. RESULTS: Energy adjusted niacin
      intake had a protective effect on development of AD and cognitive decline. In a
      logistic regression model, relative risks (95% confidence intervals) for incident
      AD from lowest to highest quintiles of total niacin intake were: 1.0 (referent)
      0.3 (0.1 to 0.6), 0.3 (0.1 to 0.7), 0.6 (0.3 to 1.3), and 0.3 (0.1 to 0.7)
      adjusted for age, sex, race, education, and ApoE e4 status. Niacin intake from
      foods was also inversely associated with AD (p for linear trend = 0.002 in the
      adjusted model). In an adjusted random effects model, higher food intake of
      niacin was associated with a slower annual rate of cognitive decline, by 0.019
      standardised units (SU) per natural log increase in intake (mg) (p = 0.05).
      Stronger associations were observed in analyses that excluded participants with a
      history of cardiovascular disease (beta = 0.028 SU/year; p = 0.008), those with
      low baseline cognitive scores (beta = 0.023 SU/year; p = 0.02), or those with
      fewer than 12 years' education (beta = 0.035 SU/year; p = 0.002) CONCLUSION:
      Dietary niacin may protect against AD and age related cognitive decline.

PMID- 15258208
TI  - Premorbid cognitive testing predicts the onset of dementia and Alzheimer's
      disease better than and independently of APOE genotype.
AB  - OBJECTIVE: To determine whether a cognitive test package can predict the onset of
      dementia up to 11 years later, and the extent to which this prediction is
      independent of that provided by APOE genotype. METHODS: Prospective cohort study
      based on 54 general practices in the UK; 657 survivors of the 1088 participants
      in the MRC treatment trial of hypertension in older adults were followed for up
      to 11 years; 370 participants (57% of survivors) were traced, screened for
      dementia, and genotyped for APOE in 1994. Baseline assessments included trail
      making test A, paired associated learning test, Raven's progressive matrices, and
      national adult reading test. At follow up, both mini-mental state examination and
      CAMCOG were used. Outcome measures were DSM-IIIR dementia and NINCDS-ADRDA
      possible and probable Alzheimer's disease. RESULTS: All the cognitive tests
      completed in 1983 predicted onset of dementia and Alzheimer's disease up to 11
      years later, as did APOE genotype. Cognitive test performance was not associated
      with APOE genotype. Addition of cognitive tests increased the area under the ROC
      curve for the prediction of Alzheimer's disease provided by age, family history,
      and APOE genotype (0.81 v 0.69, p = 0.048); addition of APOE genotype did not
      increase the area under the ROC curve for the prediction provided by age, family
      history, and cognitive tests (0.81 v 0.77, p = 0.28). CONCLUSIONS: Simple tests
      of cognitive ability provide useful predictive information up to a decade before
      the onset of dementia. The predictive information provided is independent of, but
      not enhanced by, the addition of APOE genotype.

PMID- 15258210
TI  - William John Adie (1886-1935).

PMID- 15258209
TI  - Increased intrathecal inflammatory activity in frontotemporal dementia:
      pathophysiological implications.
AB  - OBJECTIVE: Immunological mechanisms may be part of the pathophysiological
      mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of
      such mechanisms has been presented. The aim of this study was to compare the
      cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines interleukin
      (IL)-1beta and tumour necrosis factor (TNF)-alpha, and the anti-inflammatory
      cytokine transforming growth factor (TGF)-beta in patients with FTD and normal
      controls. Furthermore, serum levels of TNF-alpha, TGF-beta, and IL-1beta were
      measured in FTD patients. METHODS: The CSF levels of IL-1beta, TNFalpha, and TGF
      beta were measured using ELISA in 19 patients with FTD and 24 sex and age matched
      healthy controls. RESULTS: The CSF levels of TNF-alpha (FTD 0.6 pg/mL (median:
      lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and
      TGF-beta (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001)
      were significantly increased in FTD patients compared with controls. No
      correlations were found between CSF and serum levels of the cytokines. In the
      controls, but not in the FTD patients, a positive correlation was found between
      the CSF levels of TGF-beta and age (r = 0.42, p < 0.05). No correlation was found
      between any of the cytokines and degree of brain atrophy or white matter changes.
      No differences between the groups were found for age, gender, or CSF/serum
      albumin ratio. CONCLUSIONS: The results suggest an increased intrathecal
      production of both pro- and anti-inflammatory cytokines in FTD. As no
      correlations were found with the albumin ratio, and no correlations between CSF
      and serum levels of the cytokines were found, these changes in the CSF cannot be
      explained by a systemic overproduction of cytokines.

PMID- 15258211
TI  - Neuropsychological profile of young adults with spina bifida with or without
      hydrocephalus.
AB  - OBJECTIVES: To determine the relative impact of hydrocephalus and spinal
      dysraphism in young adults on intellectual and cognitive functioning. Sub-groups
      of patients with congenital hydrocephalus and/or spina bifida were assessed
      between 1995 and 2003. The entry criteria were that individuals should have (i)
      intact global function, (ii) average verbal intelligence (or above), and (iii)
      should not have clinical depression. There were three sub-groups: patients with
      hydrocephalus and spina bifida, patients with hydrocephalus without spina bifida,
      and patients with spina bifida without hydrocephalus. METHODS: Patients were
      neuropsychologically assessed as part of their normal clinical assessment during
      their annual medical review. Each individual completed a screening battery
      assessing global functioning, verbal intelligence, and mood. In addition they
      completed additional tests including measures of emotional intelligence, memory,
      attention, and executive function. Results were analysed to compare the
      performance of the patient sub-groups and to compare them to a healthy control
      group. RESULTS: Patients with hydrocephalus (with or without spina bifida) were
      significantly impaired on the vast majority of all test scores as compared to
      patients with spina bifida and healthy controls. They were particularly poor on
      measures assessing executive function. By contrast for patients with spina bifida
      with no associated hydrocephalus, the significant majority of all test scores
      fell within the average range or above. CONCLUSIONS: The neuropsychological
      profile of patients with hydrocephalus is one of relative impairment and this is
      so whether or not spina bifida is present. In spina bifida alone, in the absence
      of hydrocephalus, cognitive function is relatively spared.

PMID- 15258212
TI  - Psychosocial outcomes at 18 months after good neurological recovery from
      aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVES: To evaluate functioning, 18 months after surgery, of 49 patients with
      good neurological recovery following aneurysmal subarachnoid haemorrhage (SAH),
      and to determine the extent of any improvements in disturbances of mood,
      cognitive functioning, and levels of activity and participation previously
      observed at 9 month follow up. METHODS: SAH patients, matched for age, gender,
      and occupation with healthy control participants, completely quantitative
      measures of mood (HADS, FIES, BDI) and activity/participation (BICRO-39 scales),
      and a brief cognitive assessment battery (verbal fluency, digit span, prose
      recall). Controls completed the HADS and the BICRO-39. RESULTS: Patients showed
      some recovery of cognitive functioning, though impairments of prose recall
      persisted. Anxiety and depression symptoms were higher in patients than in
      controls, but fewer than 20% scored in the clinical range on any questionnaires
      except for RIES-Intrusive thoughts (22%); only three showed signs of full blown
      post-traumatic stress disorder. Almost half showed elevated dependence on others
      for domestic activities and organisation and abnormally low levels of employment.
      Very little variance in outcome was predicted by demographic variables,
      neurological or cognitive impairment, prior life stress, or mood. However, levels
      of social activity and self-organisation were related to persisting fatigue.
      CONCLUSIONS: The observed decline in intrusive thoughts and avoidance over time
      is consistent with that seen after life threatening illness or trauma. The
      persistent reductions in independence and levels of employment may in some cases
      reflect considered lifestyle adjustments rather than adverse and unwanted changes
      but in others indicate a need for focused rehabilitation.

PMID- 15258213
TI  - Two families with autosomal dominant progressive external ophthalmoplegia.
AB  - OBJECTIVES: We report here the clinical and genetic features of two new families
      with autosomal dominant progressive external ophthalmoplegia (adPEO). PATIENTS
      AND METHODS: The examination of index patients included a detailed clinical
      characterisation, histological analysis of muscle biopsy specimens, and genetic
      testing of mitochondrial and nuclear DNA extracted from muscle and leucocytes.
      RESULTS: Index patients in both families presented with PEO and developed other
      clinical disease manifestations, such as myopathy and cardiomyopathy (patient 1)
      and axonal neuropathy, diabetes mellitus, hearing loss, and myopathy (patient 2),
      later in the course of illness. Both patients had ragged red fibres on muscle
      histology. Southern blot of mtDNA from muscle of patient 2 showed multiple
      deletions. In this case, a novel heterozygous missense mutation F485L was
      identified in the nuclear encoded putative mitochondrial helicase Twinkle. The
      mutation co-segregated with the clinical phenotype in the family and was not
      detected in 150 control chromosomes. In the other index patient, sequencing of
      ANT1, C10orf2 (encoding for Twinkle), and POLG1 did not reveal pathogenic
      mutations. CONCLUSIONS: Our cases illustrate the clinical variability of adPEO,
      add a novel pathogenic mutation in Twinkle (F485L) to the growing list of genetic
      abnormalities in adPEO, and reinforce the relevance of other yet unidentified
      genes in mtDNA maintenance and pathogenesis of adPEO.

PMID- 15258214
TI  - Population based study of late onset cerebellar ataxia in south east Wales.
AB  - OBJECTIVE: To determine the prevalence and causation of late onset cerebellar
      ataxia (LOCA) in south east Wales, United Kingdom. METHODS: A population based
      study of LOCA was conducted in a defined geographical region with a total
      population of 742,400. Multiple sources of ascertainment were used to identify
      all cases prevalent on 1 January 2001. The inclusion criteria were: a
      predominantly progressive cerebellar ataxia with onset of symptoms at age > or =
      18 years; and disease duration of > or = 1 year. Cases with known acquired
      ataxias, ataxic syndromes with associated prominent autonomic dysfunction and/or
      atypical parkinsonism suggestive of multiple system atrophy and disorders with
      ataxia as a minor feature were excluded. RESULTS: We identified 76 index cases of
      LOCA, of whom 63 were sporadic, idiopathic LOCA (ILOCA) and 13 were familial
      LOCA, of whom six had either spinocerebellar ataxia type 6, Friedreich's ataxia
      or dominant episodic ataxia. The mean annual incidence rate for the period 1999
      2001 was 0.3/100,000 population/year. The crude prevalence rates were 8.4 per
      100,000 (95% CI 7.2 to 11.6) for ILOCA and 1.8 per 100,000 (95% CI 0.8 to 2.7)
      for inherited LOCA. Of the 54/63 (85.7%) patients with ILOCA who were assessed,
      mean (SD) age at onset of symptoms was 53.8 (14.1) years (range 19 to 78) with a
      male:female ratio of 2.1:1. The mean disease duration was 8.7 (6.3) years (range
      1 to 31). The most frequent presenting complaint was disturbance in gait (90.7%).
      One-third had a relatively pure cerebellar syndrome (33.3%) and two-thirds
      (66.7%) had additional extracerebellar neurological features. The majority (92%)
      were ambulant but only 9.3% were independently self-caring. CONCLUSION: This
      population based study provides insight into LOCA within a defined region and
      will inform decisions about the rational use of healthcare resources for patients
      with LOCA.

PMID- 15258215
TI  - Recommended diagnostic criteria for paraneoplastic neurological syndromes.
AB  - BACKGROUND: Paraneoplastic neurological syndromes (PNS) are defined by the
      presence of cancer and exclusion of other known causes of the neurological
      symptoms, but this criterion does not separate "true" PNS from neurological
      syndromes that are coincidental with a cancer. OBJECTIVE: To provide more
      rigorous diagnostic criteria for PNS. METHODS: An international panel of
      neurologists interested in PNS identified those defined as "classical" in
      previous studies. The panel reviewed the existing diagnostic criteria and
      recommended new criteria for those in whom no clinical consensus was reached in
      the past. The panel reviewed all reported onconeural antibodies and established
      the conditions to identify those that would be labelled as "well characterised".
      The antibody information was obtained from published work and from unpublished
      data from the different laboratories involved in the study. RESULTS: The panel
      suggest two levels of evidence to define a neurological syndrome as
      paraneoplastic: "definite" and "possible". Each level can be reached combining a
      set of criteria based on the presence or absence of cancer and the definitions of
      "classical" syndrome and "well characterised" onconeural antibody. CONCLUSIONS:
      The proposed criteria should help clinicians in the classification of their
      patients and the prospective and retrospective analysis of PNS cases.

PMID- 15258217
TI  - Positive and negative cerebral symptoms: the roles of Russell Reynolds and
      Hughlings Jackson.

PMID- 15258216
TI  - Magnetic resonance spectroscopic determination of a neuronal and axonal marker in
      white matter predicts reversibility of deficits in secondary normal pressure
      hydrocephalus.
AB  - BACKGROUND: Normal pressure hydrocephalus (NPH) is considered to be a treatable
      form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms.
      However, neuroimaging has failed to predict when shunting will be effective.
      OBJECTIVE: To investigate whether 1H (proton) magnetic resonance (MR)
      spectroscopy could predict functional outcome in patients after shunting.
      METHODS: Neurological state including Hasegawa's dementia scale, gait,
      continence, and the modified Rankin scale were evaluated in 21 patients with
      secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were
      measured postoperatively at one and 12 months and were classified as excellent,
      fair, or poor. MR spectra were obtained from left hemispheric white matter.
      RESULTS: Significant preoperative differences in N-acetyl aspartate
      (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with
      excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively).
      Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score,
      and modified Rankin scale to better one month outcome. Predictive value,
      sensitivity, and specificity for excellent outcome following shunting were 95.2%,
      100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best
      predictive value for one year outcome (p = 0.0032); predictive value,
      sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. CONCLUSIONS: MR
      spectroscopy predicted long term post-shunting outcomes in patients with
      secondary NPH, and it would be a useful assessment tool before lumbar drainage.

PMID- 15258218
TI  - Self injurious behaviour in Tourette syndrome: correlates with impulsivity and
      impulse control.
AB  - BACKGROUND: Self injurious behaviour (SIB), the deliberate, repetitive infliction
      of self harm, is present in a wide variety of neuropsychiatric disorders,
      including Tourette syndrome (TS). Although SIB occurs in up to 60% of individuals
      with TS, and can cause significant clinical impairment and distress, little is
      known about its aetiology. OBJECTIVE: This study examined the relationship
      between SIB and other behavioural features that commonly co-occur with TS in
      nearly 300 subjects with TS participating in three genetic studies. SIB,
      obsessions, compulsions, tic severity, attention deficit hyperactivity disorder
      related impulsivity, risk taking behaviours, and rages were systematically
      assessed in all subjects. METHODS: Using logistic regression, a best fit model
      was determined for both mild to moderate SIB and severe SIB. RESULTS:
      Mild/moderate SIB in TS was correlated with the presence of obsessive and
      compulsive symptoms such as the presence of aggressive obsessions or violent or
      aggressive compulsions, and with the presence of obsessive-compulsive disorder
      and overall number of obsessions. Severe SIB in TS was correlated with variables
      related to affect or impulse dysregulation; in particular, with the presence of
      episodic rages and risk taking behaviours. Both mild/moderate and severe SIB were
      also correlated with tic severity. CONCLUSIONS: This study suggests that
      mild/moderate and severe SIB in TS may represent different phenomena, which has
      implications for clinical management of these symptoms.

PMID- 15258219
TI  - Features of the Sinushunt and its influence on the cerebrospinal fluid system.
AB  - OBJECTIVES: A new cerebrospinal fluid (CSF) shunt system, Sinushunt, has recently
      been introduced. CSF is shunted from the ventricles to the transverse sinus. The
      Sinushunt is not a classical differential pressure shunt; instead, it opens as
      soon as there is a positive pressure over the shunt and the flow is dependent on
      the resistance of the system, which is high compared with traditional CSF shunts.
      The objective of this study was to characterise the features of the Sinushunt and
      to evaluate its influence on the CSF system. METHODS: Five brand new Sinushunts
      with distal catheters were tested. An automated, computerised experimental
      apparatus based on regulation of pressure, built into an incubator at 37 degrees
      C, was used. Opening pressure, resistance, and anti-reflux properties were
      determined. RESULTS: The mean (SD) opening pressure was highly dependent on the
      pressure in the sinus: P(open) = 1.3 (0.6) mm Hg with Psinus = 0.0 mm Hg, and
      Popen = 7.5 (0.6) mm Hg for Psinus = 6.5 mm Hg. The mean (SD) resistance of the
      shunts was 7.9 (0.3) mm Hg/ml/min and not clinically significantly affected by
      the sinus pressure. In one shunt there was reflux, and in another two shunts
      there was a very small, but similar, tendency. CONCLUSIONS: This study confirms
      that the resistance of the Sinushunt is comparable to the physiological values in
      humans. However, the optimal post-operative resistance for different
      hydrocephalus types is unknown, and randomised clinical trials are needed to
      confirm improved outcome and reduced complication rate for the Sinushunt compared
      with traditional low resistance ventriculoperitoneal shunts. A weakness of the
      anti-reflux system of the Sinushunt must be suspected and has to be further
      investigated.

PMID- 15258220
TI  - Profiles of brain magnetic activity during a memory task in patients with
      Alzheimer's disease and in non-demented elderly subjects, with or without
      depression.
AB  - The presence of depression is common among the elderly and it often complicates
      the early diagnosis of Alzheimer's disease (AD). In this study, we searched for
      brain activity measures that characterise AD. We compared brain magnetic activity
      profiles during a memory task, obtained from patients with AD, elderly patients
      with late onset depression, and age matched volunteers without history of
      neurological or psychiatric disease. AD patients showed significantly reduced
      activity in left temporal lobe regions during late portions of the event related
      magnetic response (400 ms or later after stimulus onset), compared with both
      groups of patients who did not present with serious cognitive decline. This
      finding highlights the potential usefulness of MEG protocols supporting the
      differential diagnosis of AD and major depression related cognitive decline in
      the elderly.

PMID- 15258221
TI  - Subacute dementia and imaging correlates in a case of Fahr's disease.
AB  - We report a case of idiopathic bilateral basal ganglia calcinosis, or Fahr's
      disease (FD) in a 50 year old patient who developed rapidly progressive
      behavioural abnormalities and severe neuropsychological impairments, but no
      movement disorder. Neuropsychological deficits included a severe dysexecutive
      syndrome, anterograde amnesia, and attentional impairment. Neuropsychiatric
      features comprised apathy with intermittent disinhibition, anxiety, irritability,
      frequent mood changes, ritualistic and antisocial behaviour, and psychosis.
      Fluorodeoxyglucose positron emission tomography showed a massive reduction of
      glucose metabolism in the basal ganglia and the frontal brain. The observed
      abnormalities possibly result from a disruption of frontostriatal circuits,
      presumably at the basal ganglia level. This case indicates that FD may cause
      exclusively behavioural alterations and that the associated hypometabolism in
      certain frontal areas is closely related to the clinical picture.

PMID- 15258222
TI  - Octapeptide repeat insertions in the prion protein gene and early onset dementia.
AB  - OBJECTIVES: The most common familial early onset dementia mutations are found in
      the genes involved in Alzheimer's disease; the amyloid precursor protein (APP)
      and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may
      be involved. METHODS: Following identification of a two-octapeptide repeat
      insertion in PRNP, we conducted a meta-analysis to investigate the relation of
      number of PRNP octapeptide repeats with age at disease onset and duration of
      illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used
      a linear mixed effects model to assess the relation of number of repeats with age
      at disease onset, and studied the effect of the number of inserted octapeptide
      repeats on disease duration with a Cox proportional hazards regression analysis.
      RESULTS: We found an increasing number of repeats associated with younger age at
      onset (p < 0.001). Duration of the disease decreased significantly with the
      length of the octapeptide repeat (p < 0.001) when adjusting for age at onset.
      CONCLUSIONS: Our findings show significant inverse associations of the length of
      the PRNP octapeptide repeat with age at disease onset and disease duration in the
      spongiform encephalopathies.

PMID- 15258223
TI  - Unusual differential diagnosis of leptomeningeal enhancement: moyamoya disease.

PMID- 15258224
TI  - Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the
      treatment of depression in patients with Parkinson's disease.
AB  - OBJECTIVE: To study the efficacy of 15 Hz repetitive transcranial magnetic
      stimulation (rTMS) in treating depression in patients with Parkinson's disease.
      METHODS: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz
      rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine
      20 mg/day. A specially designed sham coil was used for sham stimulation. The
      unified Parkinson's disease rating scale (UPDRS), activities of daily living
      (ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory
      (BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded
      to treatment arm. RESULTS: HRSD and BDI were improved to the same extent in both
      groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for
      group 2, respectively). At week 8 there was a tendency for worse motor UPDRS
      scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE
      improved in both groups after treatment, but faster in group 1 than in group 2.
      There were fewer adverse effects in group 1 than in group 2. CONCLUSIONS: rTMS
      has the same antidepressant efficacy as fluoxetine and may have the additional
      advantage of some motor improvement and earlier cognitive improvement, with fewer
      adverse effects.

PMID- 15258225
TI  - Psychological characteristics of patients with newly developed psychogenic
      seizures.
AB  - OBJECTIVES: To assess psychopathological symptoms and history of childhood trauma
      in patients with newly developed psychogenic seizures. METHODS: Using validated
      scales, 178 patients from the general population diagnosed with newly developed
      seizures were assessed, at a point in time when the nature of their seizures was
      yet unknown to either doctors or patients. After standardised neurological
      examination, 138 patients were diagnosed with non-psychogenic seizures (NPS),
      while 40 patients were found to have psychogenic seizures (PS). To evaluate
      possible differences between the genders and the diagnostic groups, univariate
      analyses of variance were done. RESULTS: PS patients reported significantly more
      comorbid psychopathological complaints, dissociative experiences, anxiety, and
      self-reported childhood trauma than NPS patients. In addition, PS patients had
      lower quality of life ratings than NPS patients. These effects were not modulated
      by gender. CONCLUSIONS: The results of the present study indicate that patients
      with newly developed PS constitute a group with complex psychopathological
      features that warrant early detection and treatment.

PMID- 15258226
TI  - Axonal degeneration and inflammation in acute optic neuritis.
AB  - AIMS: To investigate whether plasma biomarkers for axonal injury and inflammation
      are related to loss and recovery of visual function in acute optic neuritis (ON).
      METHODS: Eighteen patients with ON and 14 controls were investigated in a
      longitudinal, prospective study. Plasma phosphorylated neurofilament heavy chain
      (NfHSMI35; a surrogate marker of axonal injury), nitric oxide metabolites (NOx),
      and citrulline (surrogate markers of inflammation) were measured. RESULTS:
      Patients with ON had higher median plasma NfHSMI35 values than controls (0.17
      versus 0.005 ng/ml; p < 0.05) and higher NOx values (49 versus 35.5 microM; p <
      0.001). Plasma NfHSMI35 values correlated inversely with visual acuity at
      presentation (R = -0.67; p = 0.01). NfHSMI35 was higher in patients with poor
      recovery of visual acuity than in those with good recovery (0.25 ng/ml versus
      0.09 ng/ml; p < 0.05). Three of four patients with high NfHSMI35 and high NOx
      values experienced a poor recovery as opposed to only one of five with high NOx
      but normal NfH(SMI35) values. CONCLUSIONS: NfHSMI35, a surrogate marker for
      axonal damage, is a prognostic indicator and should be considered in the design
      of neuroprotective treatment strategies.

PMID- 15258227
TI  - Genetic heterogeneity in ten families with myoclonus-dystonia.
AB  - BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with autosomal
      dominant inheritance and reduced penetrance but may also occur sporadically.
      Recently, mutations in the epsilon-sarcoglycan gene (SGCE) were shown to cause M
      D. Furthermore, single variants in the dopamine D2 receptor (DRD2) and DYT1 genes
      were found in combination with SGCE mutations in two M-D families, and another M
      D locus was recently mapped to chromosome 18p11 in one family. METHODS: The
      authors clinically and genetically characterised ten consecutive cases with
      myoclonus-dystonia; seven familial and three sporadic. Twenty nine M-D patients
      and 40 unaffected family members underwent a standardised clinical examination by
      a movement disorder specialist. Index cases were screened for mutations in the
      SGCE, DYT1, and DRD2 genes and for deletions of the SGCE gene. Suitable mutation
      negative families were tested for linkage to the SGCE region and to chromosome
      18p11. RESULTS: Two SGCE mutations were detected among the seven familial but no
      mutation in the sporadic cases. Haplotype analysis at the new M-D locus was
      compatible with linkage in two families and excluded in another family,
      suggesting at least one additional M-D gene. There were no obvious clinical
      differences between M-D families with and without detected mutations. CONCLUSION:
      M-D is genetically heterogeneous with SGCE mutations accounting for the disease
      in only part of the clinically typical cases.

PMID- 15258228
TI  - Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect.
AB  - Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for
      approximately 20% of patients with familial amyotrophic lateral sclerosis (FALS).
      In this study, sequence analysis of exons 1-5 of SOD1 in a large German cohort
      with FALS was performed. Among 75 affected patients, who were not obviously
      related probands with a positive family history, nine had missense mutations in
      SOD1. Four of the nine probands carry the same R115G mutation in exon 4 of the
      SOD1 gene. Genotyping with markers from the SOD1 locus revealed a common
      haplotype and shared allelic characteristics in these patients. These findings
      suggest that the R115G mutation in the German population originates from a common
      founder.

PMID- 15258229
TI  - Magnetic resonance imaging abnormalities with septic encephalopathy.
AB  - A 48 year old woman, status post renal transplantation six years earlier, died
      after a two week illness characterised by fever, recurrent seizures, and coma.
      Widespread abnormalities were seen on neuroimaging. A diagnosis of septic
      encephalopathy was established on postmortem. We describe the magnetic resonance
      imaging findings of bilateral basal ganglia, thalamic, cerebellar, brainstem, and
      cerebral abnormalities in this patient, which correlate with the pathophysiology
      of septic encephalopathy.

PMID- 15258230
TI  - Raised intracranial pressure presenting with spontaneous periorbital bruising:
      two case reports.
AB  - The venous drainage of the orbit is known to be via the ophthalmic and vortex
      veins which communicate with the cavernous sinus. We describe two patients with
      raised intracranial pressure presenting with periorbital bruising. In one patient
      dural venous sinus thrombosis was demonstrated and it is suspected that the cause
      of the raised intracranial pressure may have been the same in the second. We
      suggest that the abrupt rise of pressure in the cerebral venous system was
      transmitted via the cavernous sinus to the orbital venous system.

PMID- 15258231
TI  - Dissection of the brain supplying arteries over the life span.
AB  - Cervical artery dissection (CAD) is being increasingly diagnosed due to improved
      neuroimaging methods. The mean age of patients with CAD is about 40 years, with a
      peak between 40 and 45 years of age. Proven data on the incidence of CAD in older
      patients are missing. Therefore, whether CAD should also be considered as a
      probable cause of cerebral ischemic events in the elderly was investigated. All
      consecutive patients referred to our clinic with a diagnosis of cerebral ischemia
      from January 1999 until June 2000 were thoroughly assessed for the presence of
      CAD. In addition, the records of all stroke patients treated in our department
      from January 1995 to December 1998 were analysed retrospectively for a diagnosis
      of CAD. A total of 34 patients (11 women) had suffered from internal carotid (n =
      29) or vertebral artery (n = 5) dissection. Their mean (SD) age was 50.3 (14.6)
      years, with 32.4% being older than 60 years. Clinical presentation of CAD did not
      differ depending on the patients' age. The results show that CAD is a possible
      cause of cerebral ischemia in the elderly and thus has also to be considered in
      the diagnostic investigation in this patient group.

PMID- 15258232
TI  - Is the common carotid artery intima-media thickness associated with functional
      outcome after acute ischaemic stroke?
AB  - BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is an
      independent and early marker of generalised atherosclerosis. Brain affected by
      atherosclerosis may be more vulnerable to an ischaemic insult. OBJECTIVE: To
      investigate the association between CCA-IMT and functional outcome after an acute
      ischaemic stroke. DESIGN: Prospective cohort analysis. METHODS: 284 consecutive
      patients (mean (SD) age, 68.7 (12.7) years, 126 (44%) female) with an acute
      ischaemic stroke had carotid ultrasonography, carried out by a single operator.
      Demographic data, vascular risk factors, initial stroke severity, and brain
      imaging findings were recorded. Outcome was assessed at seven days from stroke
      onset, at discharge from hospital, and at one year post-stroke. RESULTS: CCA-IMT
      was not significantly associated with adverse short or long term functional
      outcome in univariate analysis, or after adjustment in a multivariate logistic
      regression analysis for demographic data, initial stroke severity, conventional
      vascular risk factors, and the characteristics of the ischaemic lesion. Age and
      initial stroke severity were the only independent predictors of outcome.
      CONCLUSIONS: CCA-IMT was not associated with adverse functional outcome after an
      ischaemic stroke. Adding CCA-IMT in a prediction model for stroke outcome would
      probably not improve the power of the model.

PMID- 15258233
TI  - White matter abnormalities on MRI in neuroacanthocytosis.

PMID- 15258234
TI  - Disruption of facial affect processing in word deafness.

PMID- 15258235
TI  - A case of acute urinary retention caused by periaqueductal grey lesion.

PMID- 15258236
TI  - Combination of thalamic Vim stimulation and GPi pallidotomy synergistically
      abolishes Holmes' tremor.

PMID- 15258237
TI  - No association of the mitochondrial DNA A12308G polymorphism with increased risk
      of stroke in patients with the A3243G mutation.

PMID- 15258238
TI  - Early symptoms of brain tumours.

PMID- 15258239
TI  - Five year follow up of a patient with spinal and bulbar muscular atrophy treated
      with leuprorelin.

PMID- 15258240
TI  - Cessation of migraine following central retinal vein occlusion.

PMID- 15258241
TI  - Transition from paediatric to adult neurological services.

PMID- 15258242
TI  - Effect of a multidisciplinary clinic on survival in amyotrophic lateral
      sclerosis.

PMID- 15258243
TI  - Outcome of contemporary surgery for chronic subdural haematoma: evidence based
      review.

PMID- 15258244
TI  - Mesodiencephalic targeting of stimulating electrodes in patients with tremor
      caused by multiple sclerosis.

PMID- 15258245
TI  - Assessing tremor reduction and quality of life following thalamic deep brain
      stimulation for the treatment of tremor in multiple sclerosis.

PMID- 15258247
TI  - Influence of peroxisome proliferator-activated receptor gamma activation by its
      endogenous ligand 15-deoxy Delta12,14 prostaglandin J2 on nitric oxide production
      in term placental tissues from diabetic women.
AB  - Diabetes induces alterations which condition placental remodelling. The levels of
      nitric oxide (NO) (a modulator of placental invasiveness, differentiation and
      proliferation) were higher in term placental explants from diabetic patients when
      compared to controls. Peroxisome proliferator-activated receptor gamma
      (PPARgamma) activation by its endogenous ligand 15-deoxy
      Delta(12,14)prostaglandin J(2) (15dPGJ(2)), is a differentiating factor of
      adipocytes and other cell types, such as trophoblasts. 15dPGJ(2) is also able to
      down-regulate NO production in different cell types. Our study evaluated the
      levels of 15dPGJ(2) and PPARgamma and the influence of PPARgamma activation by
      15dPGJ(2) on the production of NO, in term placental tissues from control, pre
      gestational and gestational diabetic patients. Our results showed that 15dPGJ(2)
      was present in human term placenta, and that its levels were diminished in
      gestational (P<0.05) and pre-gestational (P<0.002) diabetic women when compared
      to controls. Exogenous 15dPGJ(2) addition (2 x 10(-6) mol/l) down-regulated NO
      production in placenta from control (P<0.001) and pre-gestational diabetic
      (P<0.01) patients, but failed to do so in gestational diabetic women, whose
      placental PPARgamma expression was diminished in comparison to controls
      (P<0.001). As the exogenous activation of PPARgamma prevented NO overproduction
      in placenta from pre-gestational diabetic women, it may have the potential to
      improve fetal outcome in this pathology.

PMID- 15258248
TI  - Where does bacterial replication start? Rules for predicting the oriC region.
AB  - Three methods, based on DNA asymmetry, the distribution of DnaA boxes and dnaA
      gene location, were applied to identify the putative replication origins in 120
      chromosomes. The chromosomes were classified according to the agreement of these
      methods and the applicability of these methods was evaluated. DNA asymmetry is
      the most universal method of putative oriC identification in bacterial
      chromosomes, but it should be applied together with other methods to achieve
      better prediction. The three methods identify the same region as a putative
      origin in all Bacilli and Clostridia, many Actinobacteria and gamma
      Proteobacteria. The organization of clusters of DnaA boxes was analysed in
      detail. For 76 chromosomes, a DNA fragment containing multiple DnaA boxes was
      identified as a putative origin region. Most bacterial chromosomes exhibit an
      overrepresentation of DnaA boxes; many of them contain at least two clusters of
      DnaA boxes in the vicinity of the oriC region. The additional clusters of DnaA
      boxes are probably involved in controlling replication initiation. Surprisingly,
      the characteristic features of the initiation of replication, i.e. a cluster of
      DnaA boxes, a dnaA gene and a switch in asymmetry, were not found in some of the
      analysed chromosomes, particularly those of obligatory intracellular parasites or
      endosymbionts. This is presumably connected with many mechanisms disturbing DNA
      asymmetry, translocation or disappearance of the dnaA gene and decay of the
      Escherichia coli perfect DnaA box pattern.

PMID- 15258249
TI  - Frequent recombination in telomeric DNA may extend the proliferative life of
      telomerase-negative cells.
AB  - For cells on the path to carcinogenesis, the key to unlimited growth potential
      lies in overcoming the steady loss of telomeric sequence commonly referred to as
      the 'end-replication problem' that occurs with each cell division. Most human
      tumors have reactivated telomerase, a specialized reverse transcriptase that
      directs RNA-templated addition of telomeric repeats on to chromosomal termini.
      However, approximately 10% of tumors maintain their telomeres through a
      recombination-based mechanism, termed alternative lengthening of telomeres or
      ALT. Here we demonstrate that telomeric DNA undergoes a high rate of a particular
      type of recombination visualized cytogenetically as sister chromatid exchange
      (SCE), and that this rate is dependent on genotype. A novel model of ALT is
      presented in which it is argued that telomeric exchanges, if they are unequal and
      occur at a sufficiently high frequency, will allow cells to proliferate
      indefinitely without polymerase-mediated extension of telomeric sequence.

PMID- 15258250
TI  - Design and in vivo characterization of self-inactivating human and non-human
      lentiviral expression vectors engineered for streptogramin-adjustable transgene
      expression.
AB  - Adjustable transgene expression is considered key for next-generation molecular
      interventions in gene therapy scenarios, therapeutic reprogramming of clinical
      cell phenotypes for tissue engineering and sophisticated gene-function analyses
      in the post-genomic era. We have designed a portfolio of latest generation self
      inactivating human (HIV-derived) and non-human (EIAV-based) lentiviral expression
      vectors engineered for streptogramin-adjustable expression of reporter
      (AmyS(DeltaS), EYFP, SAMY, SEAP), differentiation-modulating (human C/EBP-alpha)
      and therapeutic (human VEGF) transgenes in a variety of rodent (CHO-K1, C2C12)
      and human cell lines (HT-1080, K-562), human and mouse primary cells (NHDF, PBMC,
      CD4+) as well as chicken embryos. Lentiviral design concepts include (i) binary
      systems harboring constitutive streptogramin-dependent transactivator (PIT) and
      PIT-responsive transgene expression units on separate lentivectors; (ii)
      streptogramin-responsive promoters (P(PIR8)) placed 5' of desired transgenes;
      (iii) within modified enhancer-free 3'-long terminal repeats; and (iv)
      bidirectional autoregulated configurations providing streptogramin-responsive
      transgene expression in a lentiviral one-vector format. Rigorous quantitative
      analysis revealed HIV-based direct P(PIR)-transgene configurations to provide
      optimal regulation performance for (i) adjustable expression of intracellular and
      secreted product proteins, (ii) regulated differential differentiation of muscle
      precursor cell lines into adipocytes or osteoblasts and (iii) conditional
      vascularization fine-tuning in chicken embryos. Similar performance could be
      achieved by engineering streptogramin-responsive transgene expression into an
      autoregulated one-vector format. Powerful transduction systems equipped with
      adjustable transcription modulation options are expected to greatly advance
      sophisticated molecular interventions in clinically and/or biotechnologically
      relevant primary cells and cell lines.

PMID- 15258251
TI  - Critical role of lysine 204 in switch I region of Galpha13 for regulation of
      p115RhoGEF and leukemia-associated RhoGEF.
AB  - Heterotrimeric G proteins of the G12 family regulate the Rho GTPase through
      RhoGEFs that contain an amino-terminal regulator of G protein signaling (RGS)
      domain (RGS-RhoGEFs). Direct regulation of the activity of RGS-RhoGEFs p115 or
      leukemia-associated RhoGEF (LARG) by Galpha13 has previously been demonstrated.
      However, the precise biochemical mechanism by which Galpha13 stimulates the
      RhoGEF activity of these proteins has not yet been well understood. Based on the
      crystal structure of Galphai1 in complex with RGS4, we mutated the Galpha13
      residue lysine 204 to alanine (Galpha13K204A) and characterized the effect of
      this mutation in its regulation of RGS-RhoGEFs p115 or LARG. Compared with wild
      type Galpha13, Galpha13K204A induced much less serum-response factor activation
      when expressed in HeLa cells. Recombinant Galpha13K204A exhibits normal function
      in terms of nucleotide binding, basal GTP hydrolysis, and formation of
      heterotrimer with betagamma. We found that lysine 204 of Galpha13 is important
      for interaction with the RGS domain of p115 or LARG and for the GTPase-activating
      protein activity of these proteins. In addition, the K204A mutation of Galpha13
      impaired its regulation of the RhoGEF activity of p115 or LARG. We conclude that
      lysine 204 of Galpha13 is important for interaction with RGS-RhoGEFs and is
      critically involved in the regulation of their activity.

PMID- 15258252
TI  - Mutation in nucleotide-binding domains of sulfonylurea receptor 2 evokes Na-ATP
      dependent activation of ATP-sensitive K+ channels: implication for dimerization
      of nucleotide-binding domains to induce channel opening.
AB  - The ATP-sensitive K+ (KATP) channel is composed of a sulfonylurea receptor (SUR)
      and a pore-forming subunit, Kir6.2. SUR is an ATP-binding cassette (ABC) protein
      with two nucleotide-binding domains (NBD1 and NBD2). Intracellular ATP inhibits
      KATP channels through Kir6.2 and activates them through NBDs. However, it is
      still unknown how ATP-bound NBDs activate KATP channels. A prokaryotic ABC
      protein, MJ0796, which is entirely NBD, forms a dimer in the presence of Na-ATP
      when its glutamate at position 171 is substituted with glutamine. Mg2+ or K+
      destabilizes the dimer. We made the corresponding mutation in the NBD1 (D834N)
      and/or NBD2 (E1471Q) of SUR2A and SUR2B. As measured in the inside-out
      configuration of the patch-clamp method, SUR2x(D834N, E1471)/Kir6.2 channels
      mediated significantly larger currents in the presence of internal 1 mM Na-ATP
      than K-ATP alone or Mg-ATP. The response to Na-ATP resulted from an increase in
      the open probability but not single-channel amplitude of the channels and was
      abolished by glibenclamide (10(-5) M). In the presence of 1 mM Mg2+ -free ATP,
      Na+ increased the activity of the channels in a concentration-dependent manner.
      The Na-ATP-dependent activation was never observed with KATP channels including
      either the wild-type SUR2x, SUR2x(D834N), or SUR2x(E1471). Nicorandil activated
      SUR2x(D834N, E1471Q)/Kir6.2 channels more strongly in the presence of Na-ATP than
      K-ATP alone, whereas the reverse was true for wild-type SUR2x/Kir6.2 channels.
      Therefore, it is likely that NBDs of SUR2x dimerize in response to ATP and
      nicorandil. The dimerization induces the opening of the KATP channel, probably by
      causing a conformational change of SUR2x.

PMID- 15258253
TI  - Targeting the neighbor's pool.

PMID- 15258254
TI  - Cellular trafficking of human alpha1a-adrenergic receptors is continuous and
      primarily agonist-independent.
AB  - Alpha1a-adrenergic receptors (alpha1aARs) are present intracellularly and at the
      cell surface in cultured and natural cell models, where they are subject to
      agonist-mediated desensitization and internalization. To explore alpha1aAR
      trafficking, a hemagglutinin (HA)-tagged alpha1aAR/enhanced green fluorescent
      protein (EGFP) fusion protein was expressed in rat-1 fibroblasts and tracked by
      EGFP fluorescence and antibody labeling of surface receptors. Confocal analysis
      of antibody-labeled surface receptors revealed unexpected constitutive
      internalization in the absence of agonist stimulation. In partial agreement, the
      inverse agonist prazosin also caused a modest 20 +/- 2% increase in surface
      receptor levels, suggesting a partial block of constitutive internalization
      caused by decreased basal activation. However, prazosin was unable to prevent
      internalization of antibody-tagged surface receptors observed by confocal
      microscopy or cause obvious redistribution of intracellular receptor to the
      surface, suggesting that the alpha1aAR is internalizing even in a basal-inactive
      state. In contrast to the alpha1aAR, surface labeling of an HA-tagged alpha1b
      EGFP fusion protein did not result in any apparent constitutive internalization.
      Constitutive internalization of the alpha1aAR seems to occur alongside reversible
      agonist-induced internalization, and both seem to involve clathrin-mediated
      endocytosis but not degradation in lysozymes. Surface receptor density must be
      maintained by recycling, because the protein synthesis inhibitor cycloheximide
      has no effect on total or surface receptor density in agonist-treated or
      untreated cells for 6 h. Constitutive agonist-independent trafficking of
      alpha1aARs may provide a novel mechanism by which an internal pool of alpha1aARs
      are maintained and recycled to allow continuous agonist-induced signaling.

PMID- 15258255
TI  - The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual
      properties.
AB  - C-1305 [S-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-v-triazolo[4,5,1
      de]acridin-6-one] is a triazoloacridone with excellent activity in colon cancer
      models. The mechanism of C-1305 is unknown, although similarities in the chemical
      structure between C-1305 and amsacrine suggest common cellular targets. Here, we
      report that C-1305 is a topoisomerase II poison that is able to induce cleavable
      complexes with topoisomerase II in vitro as well as in living cells. Even at
      optimal concentrations, C-1305 is a much weaker inducer of cleavable complexes
      than amsacrine. Because the cytotoxic activities of the two compounds after
      continuous drug exposure are comparable, these findings suggest that the low
      levels of cleavable complexes induced by C-1305 may be unusually toxic. In
      contrast to amsacrine, the cytotoxicity of C-1305 is strongly time-dependent,
      with at least 24 h of drug exposure required for optimal cytotoxicity. The p53
      tumor suppressor is inactivated in the majority of human tumors, including
      colorectal cancers. We therefore compared the long-term cytotoxic effects of C
      1305, amsacrine, and doxorubicin on human cell lines in which the p53 or p21
      pathways have been specifically disrupted by targeted homologous recombination.
      Disruption of p53 and p21 had minor influence on the cytotoxicity of doxorubicin,
      whereas p53 but not p21 disruption was associated with increased resistance to
      amsacrine. In marked contrast, disruption of p53 and p21 was associated with
      increased sensitivity to C-1305. Taken together, our results show that exposure
      to C-1305 is accompanied by the formation of low levels of potent cleavable
      complexes that are selectively toxic toward tumor cells with defective p53
      function.

PMID- 15258256
TI  - Alkaloids indolizidine 235B', quinolizidine 1-epi-207I, and the tricyclic 205B
      are potent and selective noncompetitive inhibitors of nicotinic acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors are key molecules in cholinergic transmission
      in the nervous system. Because of their structural complexity, only a limited
      number of subtype-specific agonists and antagonists are available to study
      nicotinic receptor functions. To overcome this limitation, we used voltageclamp
      recordings to examine the effects of several frog skin alkaloids on acetylcholine
      elicited currents in Xenopus laevis oocytes expressing major types of neuronal
      nicotinic receptors (alpha4beta2, alpha7, alpha3beta2, alpha3beta4, and
      alpha4beta4). We found that the 5,8-disubstituted indolizidine (-)-235B' acted as
      a potent noncompetitive blocker of alpha4beta2 nicotinic receptors (IC50 = 74
      nM). This effect was highly selective for alpha4beta2 receptors compared with
      alpha3beta2, alpha3beta4, and alpha4beta4 receptors. The inhibition of
      alpha4beta2 currents by (-)-235B' was more pronounced as the acetylcholine
      concentration increased (from 10 nM to 100 microM). Moreover, the blockade of
      alpha4beta2 currents by (-)-235B' was voltage-dependent (more pronounced at
      hyperpolarized potentials) and use-dependent, indicating that (-)-235B' behaves
      as an open-channel blocker of this receptor. Several other 5,8-disubstituted
      indolizidines (5-n-propyl-8-n-butylindolizidines), two 5,6,8-trisubstituted
      indolizidines ((-)-223A and (+)-6-epi-223A), and a 1,4-disubstituted
      quinolizidine ((+)-207I) were less potent than (-)-235B', and none showed
      selectivity for alpha4beta2 receptors. The quinolizidine (-)-1-epi-207I and the
      tricyclic (+)-205B had 8.7- and 5.4-fold higher sensitivity, respectively, for
      inhibition of the alpha7 nicotinic receptor than for inhibition of the
      alpha4beta2 receptor. These results show that frog alkaloids alter the function
      of nicotinic receptors in a subtype-selective manner, suggesting that an analysis
      of these alkaloids may aid in the development of selective drugs to alter
      nicotinic cholinergic functions.

PMID- 15258257
TI  - Differential mechanisms of nitric oxide- and peroxynitrite-induced cell death.
AB  - Nitric oxide (NO) contributes to cellular degeneration in various disorders,
      particularly in the nervous system. NO targets cell proteins such as soluble
      guanylyl cyclase, but its detrimental effects are generally attributed to its
      reaction product with superoxide, peroxynitrite. To understand the mechanisms of
      NO-induced cell stress, we studied the effects of the NO donors
      diethylenetriamine and spermine NONOate and the peroxynitrite donor 5-amino-3-(4
      morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1) in SH-SY5Y and NG108-15
      neuroblastoma cells. All three compounds induced a dose- and time-dependent
      decrease in viable cells, which was not blocked by the soluble guanylyl cyclase
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. The two NONOates were
      approximately 15-fold more potent in SH-SY5Y than in NG108-15 cells, whereas the
      EC50 values of SIN-1 in SH-SY5Y and NG108-15 cells were in the same order. This
      led us to conclude that the mechanisms of NO and peroxynitrite did not converge.
      This was supported by our other findings. NONOates induced DNA fragmentation and
      an increase in cellular caspase-3 activity that preceded the gradual decline in
      cell viability. In contrast, SIN-1 induced a transient decline in ATP levels and
      a delayed loss of cell viability with no significant increase in caspase-3
      activity or DNA laddering. Moreover, post-treatment with insulin inhibited
      caspase-3 activation and loss of cell viability in NONOate- but not in SIN-1
      exposed cells. These findings suggest that NO is a potent toxin independent of
      peroxynitrite formation.

PMID- 15258258
TI  - Chronic nicotine treatment leads to induction of tyrosine hydroxylase in locus
      ceruleus neurons: the role of transcriptional activation.
AB  - Chronic nicotine treatment (two daily subcutaneous injections administered
      approximately 12 h apart for 14 days) is associated with long-term inductions of
      tyrosine hydroxylase (TH) protein and TH mRNA in locus ceruleus (LC) neurons.
      These increases persist for at least 3 days after the final nicotine injection in
      LC cell bodies and for at least 7 to 10 days in LC nerve terminal regions. We
      tested whether this long-term response is due to sustained stimulation of TH gene
      transcription rate. A semiquantitative reverse transcription-polymerase chain
      reaction assay was developed to assess changes in the levels of TH RNA primary
      transcripts; these changes are an indirect measurement of changes in TH gene
      transcription rate. TH RNA primary transcript levels increase rapidly in the LC
      after a single nicotine administration and return to basal levels by 24 h. A
      similar rapid and transient induction of LC TH RNA primary transcripts occurs
      after chronic nicotine administration. In contrast, TH RNA primary transcript
      levels remain elevated for a sustained period of time (at least 1 day) in the
      adrenal medulla after chronic nicotine administration. Similar rapid, but
      transient changes in LC TH RNA primary transcript levels are observed after
      repeated immobilization stress. These results suggest that TH gene transcription
      rate in the LC is stimulated rapidly after each nicotine injection; however, in
      contrast to the adrenal medulla, there is no sustained transcriptional response
      elicited by chronic nicotine treatment or repeated immobilization stress in the
      LC, suggesting that post-transcriptional mechanisms may also play a role in these
      long-term responses.

PMID- 15258259
TI  - Silencing the formylpeptide receptor FPR by short-interfering RNA.
AB  - A double-stranded short-interfering RNA (siRNA) was designed to attenuate the
      expression and function of the formylpeptide receptor FPR, a G protein-coupled
      receptor mediating migration and activation of phagocytic leukocytes in response
      to bacterial chemotactic formylpeptides. Retrovirus-based constructs were
      generated to introduce FPR-siRNA into a rat leukemia cell line transfected to
      overexpress FPR. Cells infected with FPR-siRNAT28, which targets the nucleotides
      926 to 944 of FPR mRNA corresponding to the third extracellular loop of the
      putative receptor protein, showed significantly reduced expression of FPR mRNA
      and protein, in association with impaired calcium mobilization and chemotactic
      responses to peptide agonists. Direct transduction of synthetic FPR-siRNAT28 into
      human macrophages also inhibited the expression of FPR and abrogated cell
      chemotaxis and the release of superoxide anions induced by the bacterial
      formylpeptide. FPR-siRNA additionally abrogated the expression and function of
      FPR in a human malignant glioma cell line. Our study demonstrates successful
      application of siRNA to silence a G protein-coupled chemoattractant receptor
      involved in inflammation and suggests the potential to use this approach in
      studies of receptor regulation and prevention of undesirable side effects
      associated with FPR activation.

PMID- 15258260
TI  - P2Y2 receptor activation regulates the expression of acetylcholinesterase and
      acetylcholine receptor genes at vertebrate neuromuscular junctions.
AB  - At the vertebrate neuromuscular junction (nmj), ATP is known to be coreleased
      with acetylcholine from the synaptic vesicles. We have previously shown that the
      P2Y1 receptor is localized at the nmj. Here, we extend the findings to show that
      another nucleotide receptor, P2Y2, is also localized there and with P2Y1 jointly
      mediates trophic responses to ATP. The P2Y2 receptor mRNA in rat muscle increased
      during development and peaked in adulthood. The P2Y2 receptor protein was shown
      to become restricted to the nmjs during embryonic development, in chick and in
      rat. In both rat and chick myotubes, P2Y1 and P2Y2 are expressed, increasing with
      differentiation, but P2Y4 is absent. The P2Y2 agonist UTP stimulated there
      inositol trisphosphate production and phosphorylation of extracellular signal
      regulated kinases, in a dose-dependent manner. These UTP-induced responses were
      insensitive to the P2Y1-specific antagonist MRS 2179 (2'-deoxy-N6-methyl
      adenosine 3',5'-diphosphate diammonium salt). In differentiated myotubes, P2Y2
      activation induced expression of acetylcholinesterase (AChE) protein (but not
      control alpha-tubulin). This was shown to arise from AChE promoter activation,
      mediated by activation of the transcription factor Elk-1. Two Elk-1-responsive
      elements, located in intron-1 of the AChE promoter, were found by mutation to act
      in this gene activation initiated at the P2Y2 receptor and also in that initiated
      at the P2Y1 receptor. Furthermore, the promoters of different acetylcholine
      receptor subunits were also stimulated by application of UTP to myotubes. These
      results indicate that ATP regulates postsynaptic gene expressions via a common
      pathway triggered by the activation of P2Y1 and P2Y2 receptors at the nmjs.

PMID- 15258261
TI  - Mre11 deficiency in Arabidopsis is associated with chromosomal instability in
      somatic cells and Spo11-dependent genome fragmentation during meiosis.
AB  - The Mre11/Rad50/Nbs1 complex is involved in many aspects of chromosome
      metabolism. Aberrant function of the complex is associated with defects in the
      DNA checkpoint, double-strand break repair, meiosis, and telomere maintenance. In
      this article, we report the consequences of Mre11 dysfunction for the stability
      of mitotic and meiotic chromosomes in Arabidopsis thaliana. Although plants
      homozygous for a T-DNA insertion in a conserved region of the MRE11 gene are
      viable, they exhibit growth defects and are infertile. Analysis of mitotic
      chromosomes prepared from the mutant plants revealed abundant dicentric
      chromosomes and chromosomal fragments. Fluorescence in situ hybridization showed
      that anaphase bridges are often formed by homologous chromosome arms. The
      frequency of chromosome fusions was not reduced in mre11 ku70 double mutants,
      suggesting that plants possess DNA end-joining activities independent of the
      Ku70/80 and Mre11 complexes. Cytogenetic examination of pollen mother cells
      revealed massive chromosome fragmentation and the absence of synapsis in the
      initial stages of meiosis. The fragmentation was substantially suppressed in
      mre11 spo11-1 double mutants, indicating that Mre11 is required for repair but
      not for the induction of Spo11-dependent meiotic DNA breaks in Arabidopsis.

PMID- 15258263
TI  - Length regulation and dynamics of individual telomere tracts in wild-type
      Arabidopsis.
AB  - Although length of the telomeric DNA tract varies widely across evolution, a
      species-specific set point is established and maintained by unknown mechanisms.
      To investigate how telomere length is controlled in Arabidopsis thaliana, we
      analyzed bulk telomere length in 14 wild-type accessions. We found that telomere
      tracts in Arabidopsis are fairly uniformly distributed throughout a size range of
      2 to 9 kb. Unexpectedly, telomeres in plants of the Wassilewskija ecotype
      displayed a bimodal size distribution, with some individuals harboring telomeres
      of 2 to 5 kb and others telomeres of 4 to 9 kb. F1 and F2 progeny of a cross
      between long and short telomere parents had intermediate telomeres, implying that
      telomere length in Arabidopsis is not controlled by a single genetic factor. We
      provide evidence that although global telomere length is strictly regulated
      within an ecotype-specific range, telomere tracts on individual chromosome ends
      do not occupy a predetermined length territory. We also demonstrate that
      individual telomere tracts on homologous chromosomes are coordinately regulated
      throughout development and that telomerase acts preferentially on the shortest
      telomeres. We propose that an optimal size for telomere tracts is established and
      maintained for each Arabidopsis ecotype.

PMID- 15258262
TI  - Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis.
AB  - MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) are small noncoding RNAs
      that have recently emerged as important regulators of mRNA degradation,
      translational repression, and chromatin modification. In Arabidopsis thaliana, 43
      miRNAs comprising 15 families have been reported thus far. In an attempt to
      identify novel and abiotic stress regulated miRNAs and siRNAs, we constructed a
      library of small RNAs from Arabidopsis seedlings exposed to dehydration,
      salinity, or cold stress or to the plant stress hormone abscisic acid. Sequencing
      of the library and subsequent analysis revealed 26 new miRNAs from 34 loci,
      forming 15 new families. Two of the new miRNAs from three loci are members of
      previously reported miR171 and miR319 families. Some of the miRNAs are
      preferentially expressed in specific tissues, and several are either upregulated
      or downregulated by abiotic stresses. Ten of the miRNAs are highly conserved in
      other plant species. Fifty-one potential targets with diverse function were
      predicted for the newly identified miRNAs based on sequence complementarity. In
      addition to miRNAs, we identified 102 other novel endogenous small RNAs in
      Arabidopsis. These findings suggest that a large number of miRNAs and other small
      regulatory RNAs are encoded by the Arabidopsis genome and that some of them may
      play important roles in plant responses to environmental stresses as well as in
      development and genome maintenance.

PMID- 15258264
TI  - Homologs of plant PsbP and PsbQ proteins are necessary for regulation of
      photosystem ii activity in the cyanobacterium Synechocystis 6803.
AB  - The mechanism of oxygen evolution by photosystem II (PSII) has remained highly
      conserved during the course of evolution from ancestral cyanobacteria to green
      plants. A cluster of manganese, calcium, and chloride ions, whose binding
      environment is optimized by PSII extrinsic proteins, catalyzes this water
      splitting reaction. The accepted view is that in plants and green algae, the
      three extrinsic proteins are PsbO, PsbP, and PsbQ, whereas in cyanobacteria, they
      are PsbO, PsbV, and PsbU. Our previous proteomic analysis established the
      presence of a PsbQ homolog in the cyanobacterium Synechocystis 6803. The current
      study additionally demonstrates the presence of a PsbP homolog in cyanobacterial
      PSII. Both psbP and psbQ inactivation mutants exhibited reduced photoautotrophic
      growth as well as decreased water oxidation activity under CaCl(2)-depleted
      conditions. Moreover, purified PSII complexes from each mutant had significantly
      reduced activity. In cyanobacteria, one PsbQ is present per PSII complex, whereas
      PsbP is significantly substoichiometric. These findings indicate that both PsbP
      and PsbQ proteins are regulators that are necessary for the biogenesis of
      optimally active PSII in Synechocystis 6803. The new picture emerging from these
      data is that five extrinsic PSII proteins, PsbO, PsbP, PsbQ, PsbU, and PsbV, are
      present in cyanobacteria, two of which, PsbU and PsbV, have been lost during the
      evolution of green plants.

PMID- 15258265
TI  - The oxylipin signal jasmonic acid is activated by an enzyme that conjugates it to
      isoleucine in Arabidopsis.
AB  - Despite its importance in a variety of plant defense responses, our understanding
      of how jasmonic acid (JA) functions at the biochemical level is limited. Several
      amino acid conjugates of JA were tested for their ability to complement the JA
      insensitive Arabidopsis thaliana mutant jar1-1. Unlike free JA, JA-Ile inhibited
      root growth in jar1-1 to the same extent as in the wild type, whereas JA-Val, JA
      Leu, and JA-Phe were ineffective inhibitors in both genotypes. Thin-layer
      chromatography and gas chromatography-mass spectrometry (GC-MS) analysis of
      products produced in vitro by recombinant JAR1 demonstrated that this enzyme
      forms JA-amido conjugates with several amino acids, including JA-Ile. JA-Val, 
      Leu, -Ile, and -Phe were each quantified in Arabidopsis seedlings by GC-MS. JA
      Ile was found at 29.6 pmole g(-1) fresh weight (FW) in the wild type but was more
      than sevenfold lower in two jar1 alleles. JA-Leu, -Val, and -Phe were present at
      only low levels in both genotypes. Expression of wild-type JAR1 in transgenic
      jar1-1 plants restored sensitivity to JA and elevated JA-Ile to the same level as
      in the wild type. The ethylene precursor 1-aminocyclopropane-1-carboxylic acid
      (ACC) conjugated to JA was also found in plant tissue at 18.4 pmole g(-1) FW. JA
      ACC was determined not be an effective jasmonate root inhibitor, and
      surprisingly, was twofold higher in the mutants than in the wild type. This
      suggests that another JA-conjugating enzyme(s) is present in Arabidopsis.
      Synthesis of JA-ACC might provide a mechanism to coregulate the availability of
      JA and ACC for conversion to the active hormones JA-Ile and ethylene,
      respectively. We conclude that JAR1 is a JA-amino synthetase that is required to
      activate JA for optimal signaling in Arabidopsis. Plant hormone activation by
      conjugation to amino acids and the enzymes involved in their formation were
      previously unknown.

PMID- 15258266
TI  - A systemic small RNA signaling system in plants.
AB  - Systemic translocation of RNA exerts non-cell-autonomous control over plant
      development and defense. Long-distance delivery of mRNA has been proven, but
      transport of small interfering RNA and microRNA remains to be demonstrated.
      Analyses performed on phloem sap collected from a range of plants identified
      populations of small RNA species. The dynamic nature of this population was
      reflected in its response to growth conditions and viral infection. The
      authenticity of these phloem small RNA molecules was confirmed by bioinformatic
      analysis; potential targets for a set of phloem small RNA species were
      identified. Heterografting studies, using spontaneously silencing coat protein
      (CP) plant lines, also established that transgene-derived siRNA move in the long
      distance phloem and initiate CP gene silencing in the scion. Biochemical analysis
      of pumpkin (Cucurbita maxima) phloem sap led to the characterization of C. maxima
      Phloem SMALL RNA BINDING PROTEIN1 (CmPSRP1), a unique component of the protein
      machinery probably involved in small RNA trafficking. Equivalently sized small
      RNA binding proteins were detected in phloem sap from cucumber (Cucumis sativus)
      and lupin (Lupinus albus). PSRP1 binds selectively to 25-nucleotide single
      stranded RNA species. Microinjection studies provided direct evidence that PSRP1
      could mediate the cell-to-cell trafficking of 25-nucleotide single-stranded, but
      not double-stranded, RNA molecules. The potential role played by PSRP1 in long
      distance transmission of silencing signals is discussed with respect to the
      pathways and mechanisms used by plants to exert systemic control over
      developmental and physiological processes.

PMID- 15258267
TI  - Import pathways of chloroplast interior proteins and the outer-membrane protein
      OEP14 converge at Toc75.
AB  - Most chloroplast outer-membrane proteins are synthesized at their mature size
      without cleavable targeting signals. Their insertion into the outer membrane is
      insensitive to thermolysin pretreatment of chloroplasts and does not require ATP.
      It has therefore been assumed that insertion of outer-membrane proteins proceeds
      through a different pathway from import into the interior of chloroplasts, which
      requires a thermolysin-sensitive translocon complex and ATP. Here, we show that a
      model outer-membrane protein, OEP14, competed with the import of a chloroplast
      interior protein, indicating that the two import pathways partially overlapped.
      Cross-linking studies showed that, during insertion, OEP14 was associated with
      Toc75, a thermolysin-resistant component of the outer-membrane protein-conducting
      channel that mediates the import of interior-targeted precursor proteins. Whereas
      almost no OEP14 inserted into protein-free liposomes, OEP14 inserted into
      proteoliposomes containing reconstituted Toc75 with a high efficiency. Taken
      together, our data indicate that Toc75 mediates OEP14 insertion, and therefore
      plays a dual role in the targeting of proteins to the outer envelope membrane and
      interior of chloroplasts.

PMID- 15258268
TI  - The SENSITIVE TO FREEZING2 gene, required for freezing tolerance in Arabidopsis
      thaliana, encodes a beta-glucosidase.
AB  - The sensitive to freezing2-1 (sfr2-1) mutation causes freezing sensitivity in
      Arabidopsis thaliana. By mapping, transgenic complementation, and sequencing,
      sfr2-1 was revealed to be a mutation in gene At3g06510. A new knockout allele was
      obtained, and its identical freezing-sensitive phenotype confirmed that the SFR2
      gene product is essential for freezing tolerance. Transcription of SFR2 was
      observed to be constitutive rather than stress inducible and was distributed
      throughout most aerial tissues. SFR2 encodes a protein homologous to family 1
      glycosyl hydrolases (beta-glycosidases), but the predicted AtSFR2 protein is
      divergent from all other family 1 beta-glycosidases of Arabidopsis, showing
      closer homology to the sequences of several beta-glycosidases from thermophilic
      archea and bacteria. After purification from a heterologous expression system,
      AtSFR2 displayed a specific hydrolytic activity against beta-d-glucosides.

PMID- 15258269
TI  - The epidemic of violence against healthcare workers.

PMID- 15258270
TI  - Assessing and intervening on OSH programmes: effectiveness evaluation of the
      Wellworks-2 intervention in 15 manufacturing worksites.
AB  - AIMS: (1) To develop a transparent and broadly applicable method for assessing
      occupational safety and health (OSH) programmes or management systems; (2) to
      assess OSH programmes in a sample of manufacturing worksites; and (3) to
      determine whether a management focused occupational health intervention results
      in greater improvement in OSH programmes compared to minimal intervention
      controls. METHODS: OSH programmes were assessed using an adaptation of the US
      Occupational Safety & Health Administration's 1995 Program Evaluation Profile.
      Scores were generated from 91 binary indicator variables grouped under four
      "Essential Elements". Essential Element scores were weighted to contribute to an
      overall programme score on a 100 point scale. Seventeen large manufacturing
      worksites were assessed at baseline; 15 sites completed the 16 month intervention
      and follow up assessments. RESULTS: There was considerable variation in Essential
      Element scores across sites at baseline as judged by our instrument, particularly
      in "management commitment and employee participation" and "workplace analysis".
      Most sites scored highly on "hazard prevention and control" and "training and
      education". For overall OSH programme scores, most sites scored in the 60-80%
      range at baseline, with four sites scoring below 60%, suggesting weak programmes.
      Intervention sites showed greater improvements than controls in the four
      programme elements and in overall programme scores, with significantly greater
      improvements in "management commitment and employee participation". CONCLUSIONS:
      The OSH programme assessment method used is broadly applicable to manufacturing
      work settings, and baseline profiles suggest needs for improvement in OSH
      programmes in most such worksites. Despite a small sample size, results showed
      that sustained management focused intervention can result in improvement in these
      OSH programme measures.

PMID- 15258271
TI  - The association between occupational factors and adverse health outcomes in
      chronic obstructive pulmonary disease.
AB  - BACKGROUND AND AIMS: Despite recognition that occupational exposures may make a
      substantive contribution to the aetiology of COPD, little is known about the
      potential role of work related factors in COPD related health outcomes. METHODS:
      Prospective cohort study using structured telephone interviews among a random
      sample of adults aged 55-75 reporting a COPD condition (emphysema, chronic
      bronchitis, or COPD). Using multivariate models adjusting for smoking and
      demographic factors, the separate and combined associations were estimated
      between occupational exposure to vapours, gas, dust, or fumes (VGDF) and leaving
      work due to lung disease (respiratory related work disability) with health
      outcomes and utilisation ascertained at one year follow up. RESULTS: Of 234
      subjects, 128 (55%) reported exposure to VGDF on their longest held jobs, 58
      (25%) reported respiratory related work disability, and 38 (16%) subjects
      reported both. Combined exposure to VGDF and respiratory related work disability
      (rather than either factor alone) was associated with the greatest risk at follow
      up of frequent (everyday) restricted activity days attributed to a breathing or
      lung condition (OR 3.8; 95% CI 1.4 to 10.1), emergency department (ED) visit (OR
      3.9; 95% CI 1.4 to 10.5), and hospitalisation (OR 7.6; 95% CI 1.8 to 32).
      CONCLUSIONS: Among persons with COPD, past occupational exposures and work
      disability attributed to lung disease, particularly in combination, appear to be
      risk factors for adverse health related outcomes.

PMID- 15258272
TI  - Ergonomic stressors and upper extremity musculoskeletal disorders in automobile
      manufacturing: a one year follow up study.
AB  - AIMS: To estimate the one year cumulative incidence and persistence of upper
      extremity (UE) soft tissue disorders, in a fixed cohort of automotive
      manufacturing workers, and to quantify their associations with ergonomic
      exposures. METHODS: At baseline and at follow up, cases of UE musculoskeletal
      disorders were determined by interviewer administered questionnaire and
      standardised physical examination of the upper extremities. The interview
      obtained new data on psychosocial strain and updated the medical and work
      histories. An index of exposure to ergonomic stressors, obtained at baseline
      interview, was the primary independent variable. Cumulative incidence and
      persistence of UE disorders (defined both by symptoms and by physical examination
      plus symptoms) were analysed in relation to baseline ergonomic exposures,
      adjusting for other covariates. The incidence of new disorders was modelled using
      multivariate proportional hazards regression among workers who were not cases in
      the first year and the prevalence on both occasions was modelled by repeated
      measures analysis. RESULTS: A total of 820 workers (69% of eligible cohort
      members) was examined. Follow up varied slightly by department group but not by
      baseline exposure level or other characteristics. Among the non-cases at
      baseline, the cumulative incidence of UE disorders was 14% by symptoms and 12% by
      symptoms plus examination findings. These rates increased with index of physical
      exposures primarily among subjects who had the same jobs at follow up as at
      baseline. Increased exposure during follow up increased risk of incidence. The
      persistence of UE disorders from baseline to follow up examination was nearly 60%
      and somewhat associated with baseline exposure score. CONCLUSIONS: These
      longitudinal results confirm the previous cross sectional associations of UE
      musculoskeletal disorders with exposure to combined ergonomic stressors. The
      exposure-response relation was similar for incident cases defined by symptoms
      alone and those confirmed by physical examination.

PMID- 15258273
TI  - No association between the use of cellular or cordless telephones and salivary
      gland tumours.
AB  - AIM: To investigate the association between the use of cellular or cordless
      telephones and the risk for salivary gland tumours. METHODS: Cases were assessed
      from the six regional cancer registries in Sweden. Four controls matched for sex
      and age in five year age groups were selected for each case. A total of 293
      living cases and 1172 controls were included. RESULTS: There were 267 (91%)
      participating cases and 1053 (90%) controls. Overall no significantly increased
      risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue
      phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI
      0.68 to 1.43) for use of cordless phones. Similar results were found for
      different salivary gland localisations. No effect of tumour induction period or
      latency was seen, although few subjects reported use for more than 10 years.
      CONCLUSIONS: No association between the use of cellular or cordless phones and
      salivary gland tumours was found, although this study does not permit conclusions
      for long term heavy use.

PMID- 15258274
TI  - Mortality and cancer incidence among alachlor manufacturing workers 1968-99.
AB  - BACKGROUND: Alachlor is the active ingredient in pre-emergent herbicide
      formulations that have been used widely on corn, soybeans, and other crops. It
      has been found to cause nasal, stomach, and thyroid tumours in rodent feeding
      studies at levels that are much higher than likely human exposures. AIMS: To
      evaluate mortality rates from 1968 to 1999 and cancer incidence rates from 1969
      to 1999 for alachlor manufacturing workers at a plant in Muscatine, Iowa.
      METHODS: Worker mortality and cancer incidence rates were compared to
      corresponding rates for the Iowa state general population. Analyses addressed
      potential intensity and duration of exposure. RESULTS: For workers with any
      period of high alachlor exposure, mortality from all causes combined was lower
      than expected (42 observed deaths, SMR 64, 95% CI 46 to 86) and cancer mortality
      was slightly lower than expected (13 observed deaths, SMR 79, 95% CI 42 to 136).
      Cancer incidence for workers with potential high exposure was similar to that for
      Iowa residents, both overall (29 observed cases, SIR 123, 95% CI 82 to 177) and
      for workers exposed for five or more years and with at least 15 years since first
      exposure (eight observed cases, SIR 113, 95% CI 49 to 224). There were no cases
      of nasal, stomach, or thyroid cancer. CONCLUSIONS: There were no cancers of the
      types found in toxicology studies and no discernible relation between cancer
      incidence for any site and years of alachlor exposure or time since first
      exposure. Despite the small size of this population, the findings are important
      because these workers had chronic exposure potential during extended
      manufacturing campaigns, while use in agriculture is typically limited to a few
      days or weeks each year.

PMID- 15258275
TI  - Lung function changes in coke oven workers during 12 years of follow up.
AB  - AIMS: To investigate the effect of exposure to coke oven emissions on the lung
      function of coke oven workers. METHODS: The study population, followed from 1978
      and 1990, was 580 male workers with at least two sets of lung function
      measurements (FVC, FEV1, FEV1/FVC, and FEF25-75%). An annual rate of change (time
      slope) for age and height adjusted lung function index was estimated for each
      subject. This "time slope" was then treated as the response variable in a
      weighted multiple regression analysis with selected predictors. RESULTS: For all
      580 subjects, each year of working in the "operation" group (the most exposed)
      was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3
      ml/year). After the exclusion of 111 subjects without detailed work history, the
      above finding was confirmed and each year of exposure in "operation" was also
      found to increase the FEV1 decline by around 0.8 ml/year (95% CI 0.1 to 1.4
      ml/year). CONCLUSIONS: These findings are consistent with the results of previous
      cross-sectional studies. Work duration in the most exposed position in the coke
      ovens was associated with increased annual decline for FVC and FEV1. The
      estimated effect of one year of work exposure in "operation" is equivalent, in
      terms of the reduction in lung function, to an estimated 2.1 pack-years of
      smoking for FVC and 1.2 pack-years of smoking for FEV1.

PMID- 15258276
TI  - Increased urinary excretion of 8-hydroxydeoxyguanosine in engine room personnel
      exposed to polycyclic aromatic hydrocarbons.
AB  - BACKGROUND: Previous investigations indicate that engine room personnel on ships
      are exposed to polycyclic aromatic hydrocarbons (PAH) from oil and oil products,
      with dermal uptake as the major route of exposure. Several PAH are known
      carcinogens and mutagens. AIMS: To investigate the urinary excretion of a marker
      for oxidative DNA damage, 8-hydroxydeoxy-guanosine (8OHdG), in engine room
      personnel, and to study the association between 8OHdG and 1-hydroxypyrene (1OHP),
      a biological marker for PAH exposure. METHODS: Urine samples were collected from
      engine room personnel (n = 36) on 10 Swedish and Norwegian ships and from
      unexposed controls (n = 34) with similar age and smoking habits. The exposure to
      oils, engine exhaust, and tobacco smoke 24 hours prior to sampling was estimated
      from questionnaires. The urinary samples were frozen for later analyses of 8OHdG
      and 1OHP by high performance liquid chromatography. RESULTS: Excretion in urine
      of 8OHdG (adjusted to density 1.022) was similar for controls (mean 18.0 nmol/l,
      n = 33), and for those who had been in the engine room without skin contact with
      oils (mean 18.7 nmol/l, n = 15). Engine room personnel who reported skin contact
      with oil had increased excretion of 8OHdG (mean 23.2 nmol/l, n = 19). The
      difference between this group and the unexposed controls was significant. The
      urinary levels of ln 1OHP and ln 8OHdG were significantly correlated, and the
      association was still highly significant when the effects of smoking and age were
      accounted for in a multiple regression analysis. CONCLUSION: Results indicate
      that exposure to PAH or possibly other compounds from skin contact with oils in
      engine rooms may cause oxidative DNA damage.

PMID- 15258277
TI  - Evaluation of the protective effectiveness of gloves from occupational exposure
      to 2-methoxyethanol using the biomarkers of 2-methoxyacetic acid levels in the
      urine and plasma.
AB  - AIMS: To evaluate the protective effectiveness of gloves from occupational
      exposure to 2-methoxyethanol (2-ME); and to examine the association of 2
      methoxyacetic acid (MAA) in urine and plasma collected simultaneously from low 2
      ME exposure and high 2-ME exposure workers in a semiconductor copper laminate
      circuit board manufacturing plant. METHODS: Eight hour time weighted breathing
      zone monitoring was performed to verify the 2-ME exposure classification between
      workers in regular and special operations. Urine and plasma samples were
      simultaneously collected from 74 exposed and 80 non-exposed workers. MAA
      concentrations in the urine (UMAA) and plasma (PMAA) were measured using
      previously published methods. Three types of gloves worn by workers (cotton,
      rubber, and no gloves) were recorded by direct observations in the workplace and
      validated by person-to-person interview. Protective effectiveness indices (PEI)
      were used to evaluate the glove effectiveness. RESULTS: There was no detectable 2
      ME/MAA in the air, or in urine and plasma samples in non-exposed workers. The
      average UMAA and PMAA in special operations were 72.63 mg/g Cr. and 29.72 mg/l,
      significantly higher than values in regular operations (5.44 mg/g Cr. and 2.58
      mg/l, respectively). PMAA showed satisfactory correlation to UMAA in all
      participants from both regular and special operations. The rubber gloves provided
      significant reduction in 2-ME uptake, whereas cotton gloves provided little
      protection with fluctuating effectiveness, based on PEI estimates. CONCLUSIONS:
      PMAA, similar to UMAA, could serve as a specific biomarker for 2-ME exposure.
      Wearing impermeable rubber gloves during high risk tasks can reduce major 2-ME
      exposure. Other improvements, including engineering control, should be provided
      to diminish worker exposure to 2-ME in occupational environments.

PMID- 15258278
TI  - Determination of serum IgG antibodies to Bacillus anthracis protective antigen in
      environmental sampling workers using a fluorescent covalent microsphere
      immunoassay.
AB  - AIMS: To evaluate potential exposure to Bacillis anthracis (Ba) spores in
      sampling/decontamination workers in the aftermath of an anthrax terror attack.
      METHODS: Fifty six serum samples were obtained from workers involved in
      environmental sampling for Ba spores at the American Media, Inc. (AMI) building
      in Boca Raton, FL after the anthrax attack there in October 2001. Nineteen sera
      were drawn from individuals both pre-entry and several weeks after entrance into
      the building. Nine sera each were drawn from unique individuals at the pre-entry
      and follow up blood draws. Thirteen donor control sera were also evaluated.
      Individuals were surveyed for Ba exposure by measurement of serum Ba anti
      protective antigen (PA) specific IgG antibodies using a newly developed
      fluorescent covalent microsphere immunoassay (FCMIA). RESULTS: Four sera gave
      positive anti-PA IgG results (defined as anti-PA IgG concentrations > or = the
      mean microg/ml anti-PA IgG from donor control sera (n = 13 plus 2 SD which were
      also inhibited > or = 85% when the serum was pre-adsorbed with PA). The positive
      sera were the pre-entry and follow up samples of two workers who had received
      their last dose of anthrax vaccine in 2000. CONCLUSION: It appears that the
      sampling/decontamination workers of the present study either had insufficient
      exposure to Ba spores to cause the production of anti-PA IgG antibodies or they
      were exposed to anthrax spores without producing antibody. The FCMIA appears to
      be a fast, sensitive, accurate, and precise method for the measurement of anti-PA
      IgG antibodies.

PMID- 15258279
TI  - Asymptomatic sensitisation to grapes in a sample of workers in the wine industry.
AB  - AIMS: To assess the prevalence of sensitisation to grapes (Vitis vinifera var.
      agiorghitiko) in a population with repeated exposure to grape allergens through
      direct cutaneous contact as well as through the gastrointestinal tract. METHODS:
      One hundred and twenty subjects were enrolled in each of four groups: grape
      harvesters, winery workers in selection of grapes, winery workers operating de
      stemming/crushing/pressing machines, and administrative personnel. Sensitisation
      to grapes was examined by skin prick-to-prick tests with fresh fruit and juice.
      RESULTS: Eight harvesters and five workers in grape selection had positive
      reaction to the grapes tested. No machine operators or administrative personnel
      had positive tests. The likelihood of sensitisation was estimated at 3.7% per
      year of occupation by logistic regression analysis. None of the employees
      reported symptoms associated with sensitisation to grapes. CONCLUSION:
      Asymptomatic sensitisation to grapes was detected only in workers handling the
      fruit, suggesting that sensitisation is more likely to occur through cutaneous
      exposure and/or minor wounding than through the gastrointestinal tract.
      Prevalence rates were high and the clinical impact needs to be further
      investigated.

PMID- 15258280
TI  - Reactive airways dysfunction syndrome caused by bromochlorodifluoromethane from
      fire extinguishers.
AB  - Although the neurological and cardiovascular effects of Freons have been
      extensively described, the respiratory effects have been less well documented. We
      report four cases of occupational asthma following accidental exposure to
      bromochlorodifluoromethane (Halon 1211) due to release of the contents of a fire
      extinguisher. All subjects developed an irritative reaction of the upper airways
      and lower respiratory symptoms immediately after exposure. Non-specific bronchial
      hyperreactivity was present for at least two months in all subjects and was still
      present more than two years after exposure in one case. The diagnosis of reactive
      airways dysfunction syndrome can be adopted in at least three of these four
      cases.

PMID- 15258281
TI  - Urinary excretion half life of trichloroacetic acid as a biomarker of exposure to
      chlorinated drinking water disinfection by-products.
AB  - AIMS: To measure accurately urinary elimination half life of trichloroacetic acid
      (TCAA). METHODS: A longitudinal pilot exposure/intervention study measured the
      elimination half life of TCAA in urine. Beverage consumption was limited to a
      public water supply and bottled water of known TCAA concentration, and ingestion
      volume was managed. The five participants limited fluid consumption to only the
      water provided. Consumption journals were kept by each participant and their
      daily first morning urine (FMU) samples were analysed for TCAA and creatinine.
      TCAA elimination half life curves were generated from a two week washout period
      using TCAA-free bottled water. RESULTS: Individual elimination half lives ranged
      from 2.1 to 6.3 days, for single compartment exponential decay, the model which
      fit the data. CONCLUSION: Urinary TCAA is persistent enough to be viable as a
      biomarker of medium term (days) exposure to drinking water TCAA ingestion within
      a range of realistic concentrations.

PMID- 15258282
TI  - Excess risk of kidney disease in a population living near industrial plants.
AB  - Runcorn has been a site of chemical industry activity for over a century, where
      tons of toxic chemicals are released annually to air and water. Excess kidney
      disease mortality (nephritis, nephrotic syndrome, and nephrosis) was found in the
      population living within 2 km of the industrial plants (standardised mortality
      ratio (SMR) in males 131 (95% CI 90 to 185) and females 161 (95% CI 118 to 214))
      compared to a reference population (northwest England)). Risk of hospital
      admissions for kidney disease in Halton (comprising the towns of Runcorn and
      Widnes) was higher than in the less industrial, nearby town of Warrington. The
      standardised admission ratio (SAR) in Halton was 115 (95% CI 107 to 124) for
      males and 126 (95% CI 117 to 137) for females; and in Warrington 91 (95% CI 85 to
      97) for males and 84 (95% CI 78 to 91) for females compared to the Warrington and
      Halton area as a whole. The excess risk of kidney disease in the Runcorn area
      requires further investigation.

PMID- 15258283
TI  - Can delta-aminolevulinic acid dehydratase 2 allele exert certain protective
      measures against the neurotoxic effects of lead?

PMID- 15258284
TI  - Current concepts of irritant contact dermatitis.

PMID- 15258285
TI  - Membrane lipid patterns typify distinct anaerobic methanotrophic consortia.
AB  - The anaerobic oxidation of methane (AOM) is one of the major sinks of this
      substantial greenhouse gas in marine environments. Recent investigations have
      shown that diverse communities of anaerobic archaea and sulfate-reducing bacteria
      are involved in AOM. Most of the relevant archaea are assigned to two distinct
      phylogenetic clusters, ANME-1 and ANME-2. A suite of specific (13)C-depleted
      lipids demonstrating the presence of consortia mediating AOM in fossil and recent
      environments has been established. Here we report on substantial differences in
      the lipid composition of microbial consortia sampled from distinct compartments
      of AOM-driven carbonate reefs growing in the northwestern Black Sea. Communities
      in which the dominant archaea are from the ANME-1 cluster yield internally
      cyclized tetraether lipids typical of thermophiles. Those in which ANME-2 archaea
      are dominant yield sn-2-hydroxyarchaeol accompanied by crocetane and crocetenes.
      The bacterial lipids from these communities are also distinct even though the
      sulfate-reducing bacteria all belong to the Desulfosarcina/Desulfococcus group.
      Nonisoprenoidal glycerol diethers are predominantly associated with ANME-1
      dominated communities. Communities with ANME-2 yield mainly conventional, ester
      linked diglycerides. ANME-1 archaea and associated sulfate-reducing bacteria seem
      to be enabled to use low concentrations of methane and to grow within a broad
      range of temperatures. Our results offer a tool for the study of recent and
      especially of fossil methane environments.

PMID- 15258286
TI  - Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not
      memory T lymphocyte responses.
AB  - Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T
      lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T
      lymphocyte response remain unclear. We explored this issue in the simian human
      immunodeficiency virus/rhesus monkey model in the course of assessing the
      relative immunogenicity of vaccine regimens that included a cytokine-augmented
      plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant
      vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant
      fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude
      of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus
      boosted monkeys was substantially greater than that seen in the monkeys immunized
      with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses
      decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys
      by the time of viral challenge. Consistent with these comparable memory T cell
      responses, the clinical protection seen in all groups of experimentally
      vaccinated monkeys was similar. This study, therefore, indicates that the steady
      state memory, rather than the peak effector vaccine-elicited T lymphocyte
      responses, may be the critical immune correlate of protection for a CTL-based HIV
      vaccine.

PMID- 15258287
TI  - Biological activity of nitric oxide in the plasmatic compartment.
AB  - There exist reaction products of nitric oxide (NO) with blood that conserve its
      bioactivity and transduce an endocrine vasomotor function under certain
      conditions. Although S-nitrosated albumin has been considered the major species
      subserving this activity, recent data suggest that additional NO species, such as
      nitrite, nitrated lipids, N-nitrosamine, and iron-nitrosyl complexes, may
      contribute. We therefore examined the end products of NO reactions in plasma and
      blood in vitro and in vivo by using reductive chemiluminescent assays and
      electron paramagnetic resonance spectroscopy. We found that NO complexes in
      plasma previously considered to be S-nitrosated albumin were <10 nM after
      elimination of nitrite and were mercury-stable, consistent with iron-nitrosyl or
      N-nitrosamine complex. During clinical NO gas inhalation protocols or in vitro NO
      donor treatment of human plasma, S-nitroso-albumin did not form with NO exposure
      <2 microM, but plasma methemoglobin was detectable by paramagnetic resonance
      spectroscopy. Consistent with this formation of methemoglobin, human plasma was
      found to consume approximately 2 microM NO at a rate equivalent to that of
      hemoglobin. This NO consumption was mediated by the reaction of NO with plasma
      haptoglobin-hemoglobin complexes and limited slower reaction pathways required
      for S-nitrosation. These data suggest that high-affinity, metal-based reactions
      in plasma with the haptoglobin-hemoglobin complex modulate plasmatic NO reaction
      products and limit S-nitrosation at low NO flux. The studies further suggest that
      alternative NO reaction end products in plasma, such as nitrite, N-nitrosamines,
      iron-nitrosyls, and nitrated lipids, should be evaluated in blood NO transport
      along the vasculature.

PMID- 15258288
TI  - Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at the single
      molecule level.
AB  - IgG transport within and across cells is essential for effective humoral
      immunity. Through a combination of biochemical and in vivo analyses, the MHC
      class I-related neonatal Fc receptor (FcRn) is known to play a central role in
      delivering IgGs within and across cells. However, little is known about the
      molecular and cellular mechanisms that are involved in the exocytosis of IgG from
      cells that express FcRn. Here, we use single-molecule fluorescence microscopy to
      analyze exocytic processes in FcRn-GFP-transfected human endothelial cells. We
      show that exocytosis can occur by means of multiple modes that range from
      complete fusion of the exocytic vesicle with the plasma membrane to a slower
      release mode ("prolonged release") that only involves partial mixing of membrane
      contents. Even for prolonged release, diffusion of FcRn into the plasma membrane
      can occur, indicating that FcRn is directly involved in IgG exocytosis. The
      slower-release mode is characterized by periodic, stepwise release of IgG, rather
      than the rapid burst that is observed for complete-fusion events. Analyses of
      single-molecule tracks suggest that IgG may be bound to FcRn for several seconds
      after exocytosis. Unexpectedly, after diffusion out of the exocytic site, IgG and
      FcRn molecules can also migrate back into the epicenter of the release site. Such
      retrograde movement may represent a mechanism for FcRn retrieval. Our studies
      provide insight into the events that lead to IgG exocytosis.

PMID- 15258289
TI  - Characterization of synthetic DNA bar codes in Saccharomyces cerevisiae gene
      deletion strains.
AB  - Incorporation of strain-specific synthetic DNA tags into yeast Saccharomyces
      cerevisiae gene-deletion strains has enabled identification of gene functions by
      massively parallel growth rate analysis. However, it is important to confirm the
      sequences of these tags, because mutations introduced during construction could
      lead to significant errors in hybridization performance. To validate this
      experimental system, we sequenced 11,812 synthetic 20-mer molecular bar codes and
      adjacent sequences (>1.8 megabases synthetic DNA) by pyrosequencing and Sanger
      methods. At least 31% of the genome-integrated 20-mer tags contain differences
      from those originally synthesized. However, these mutations result in anomalous
      hybridization in only a small subset of strains, and the sequence information
      enables redesign of hybridization probes for arrays. The robust performance of
      the yeast gene-deletion dual oligonucleotide bar-code design in array
      hybridization validates the use of molecular bar codes in living cells for
      tracking their growth phenotype.

PMID- 15258290
TI  - Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration.
AB  - Integrated hepadnaviral DNA in livers and tumors of chronic hepatitis B patients
      has been reported for many years. In this study, we investigated whether
      hepatitis B virus DNA integration occurs preferentially at sites of cell DNA
      damage. A single I-SceI homing endonuclease recognition site was introduced into
      the DNA of the chicken hepatoma cell line LMH by stable DNA transfection, and
      double-strand breaks were induced by transient expression of I-SceI after
      transfection of an I-SceI expression vector. Alteration of the target cleavage
      site by imprecise nonhomologous end joining occurred at a frequency of
      approximately 10(-3) per transfected cell. When replication of an avian
      hepadnavirus, duck hepatitis B virus, occurred at the time of double-strand break
      repair, we observed integration of viral DNA at the site of the break with a
      frequency of approximately 10(-4) per transfected cell. Integration depended on
      the production of viral double-stranded linear DNA and the expression of I-SceI,
      and integrated DNA was stable through at least 17 cell divisions. Integration
      appeared to occur through nonhomologous end joining between the viral linear DNA
      ends and the I-SceI-induced break, because small deletions or insertions were
      observed at the sites of end joining. The results suggest that integration of
      hepadnaviral DNA in infected livers occurs at sites of DNA damage and may
      indicate the presence of more widespread genetic changes beyond that caused by
      viral DNA integration itself [corrected].

PMID- 15258291
TI  - Prospects for inferring very large phylogenies by using the neighbor-joining
      method.
AB  - Current efforts to reconstruct the tree of life and histories of multigene
      families demand the inference of phylogenies consisting of thousands of gene
      sequences. However, for such large data sets even a moderate exploration of the
      tree space needed to identify the optimal tree is virtually impossible. For these
      cases the neighbor-joining (NJ) method is frequently used because of its
      demonstrated accuracy for smaller data sets and its computational speed. As data
      sets grow, however, the fraction of the tree space examined by the NJ algorithm
      becomes minuscule. Here, we report the results of our computer simulation for
      examining the accuracy of NJ trees for inferring very large phylogenies. First we
      present a likelihood method for the simultaneous estimation of all pairwise
      distances by using biologically realistic models of nucleotide substitution. Use
      of this method corrects up to 60% of NJ tree errors. Our simulation results show
      that the accuracy of NJ trees decline only by approximately 5% when the number of
      sequences used increases from 32 to 4,096 (128 times) even in the presence of
      extensive variation in the evolutionary rate among lineages or significant biases
      in the nucleotide composition and transition/transversion ratio. Our results
      encourage the use of complex models of nucleotide substitution for estimating
      evolutionary distances and hint at bright prospects for the application of the NJ
      and related methods in inferring large phylogenies.

PMID- 15258292
TI  - A (very) short history of diets for gout.

PMID- 15258293
TI  - Uptake of influenza vaccination in rheumatology patients.

PMID- 15258294
TI  - Rheumatologists and breasts: immunosuppressive therapy for granulomatous
      mastitis.

PMID- 15258295
TI  - Bilateral anterior uveitis as an unusual manifestation of Kikuchi-Fujimoto
      disease.

PMID- 15258296
TI  - Are evidence-based guidelines being followed for the monitoring of ocular
      toxicity of hydroxychloroquine? A nationwide survey of practice amongst
      consultant rheumatologists and implications for clinical governance. Comment on
      the article by Samanta et al.

PMID- 15258297
TI  - Adherence to guidelines for the monitoring of antimalarial-related retinal
      toxicity.

PMID- 15258299
TI  - Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis.

PMID- 15258300
TI  - Methotrexate and folic acid: what is the optimal combination?

PMID- 15258302
TI  - Joint examination skills: are rheumatology specialist registrars adequately
      trained?

PMID- 15258304
TI  - Comparison of different kits in the detection of autoantibodies to cardiolipin
      and [beta]2-glycoprotein 1: comment on the article by Audrain et al.

PMID- 15258307
TI  - Responses against complex antigens in various models of CD4 T-cell deficiency:
      surprises from an anti-CD4 antibody transgenic mouse.
AB  - The most common models of CD4 T-cell deficiency are mice exogenously injected
      with anti-CD4 antibody (Ab), CD4 knockout (CD4-/-) and major histocompatibility
      complex (MHC) class II knockout (class II-/-) mice. We recently described the
      anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This
      review compares this new GK mouse model with the widely available class II-/- and
      CD4-/- mice, when exposed to complex antigens (foreign grafts and during
      bacterial or viral infection). We highlight here the cytometric and functional
      differences (including Ab isotype, viral or bacterial clearance, and graft
      survival) among these CD4 cell-deficient models. For example, whereas grafts are
      generally rejected in class II-/- and CD4-/- mice as quickly as in wild-type
      mice, they survive longer in GK mice. Also, CD4-/- mice produce IgG against both
      simple model and complex antigens, but class II-/- and GK mice produce small
      amounts of IgG2a against complex antigens but not simple model antigens. These
      differences harbinger the caveats in the use of these various mice.

PMID- 15258308
TI  - Manipulation of iron to determine survival: competition between host and
      pathogen.
AB  - Iron is an essential nutrient that can determine cellular survival. Many
      organisms have evolved sophisticated mechanisms for iron uptake and transport to
      support their growth. The dual dependence on iron of both the host and invading
      pathogen initiates a competition for this nutrient following infection.
      Microorganisms have developed various strategies to acquire iron from the host.
      These are counter-balanced by an iron-withholding strategy that the host deploys
      as part of its defense system. This strategy, involving many iron-regulatory
      proteins, mediates iron depletion at the mucosal surfaces, in the extracellular
      environment, and within the cells. Iron is sequestered into storage by the host
      in order to deprive the pathogens of this factor and to prevent their
      proliferation. This system can be compromised. In particular, new evidence is
      emerging that suggests that viruses are able to specifically target and regulate
      proteins involved in iron homeostasis. This review focuses on the procedures
      employed by the host and viruses to regulate iron as a means of defense and
      survival, respectively.

PMID- 15258309
TI  - The role of CD94/NKG2 in innate and adaptive immunity.
AB  - CD94/NKG2 is a heterodimer expressed on natural killer (NK) and a small subset of
      T cells. This receptor varies in function as an inhibitor or activator depending
      on which isoform of NKG2 is expressed. The ligand for CD94/NKG2 is HLA-E in human
      and its homolog, Qa1 in mouse, which are both nonclassical class I molecules that
      bind leader peptides from other class I molecules. Although <5% of CD8 T cells
      express the receptor in a naive mouse, its expression is upregulated upon
      specific recognition of antigen. Similar to NK cells, most CD8 T cells that
      express high levels of CD94 co-express NKG2A, the inhibitory isoform. The
      engagement of this receptor can lead to a blocking of cytotoxicity. However,
      these receptors have also been implicated in the cell survival of both NK and CD8
      T cells. The level of CD94 expression is inversely correlated with the level of
      apoptosis in culture. Thus, CD94/NKG2 receptors may regulate effector functions
      and cell survival of NK cells and CD8 T cells, thereby playing a crucial role in
      the innate and adaptive immune response to a pathogen.

PMID- 15258311
TI  - The role of complement activation in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease in which dyslipidemia,
      inflammation, and the immune system play an important pathogenetic role. A role
      in atherogenesis was demonstrated for monocyte/macrophages, complement system,
      and T-lymphocytes. Complement activation and C5b-9 deposition occurs both in
      human and experimental atherosclerosis. Complement C6 deficiency has a protective
      effect on diet-induced atherosclerosis, indicating that C5b-9 assembly is
      required for the progression of atherosclerotic lesions. The maturation of
      atherosclerotic lesions beyond the foam cell stage was shown to be strongly
      dependent on an intact complement system. C5b-9 may be responsible for cell
      lysis, and sublytic assembly of C5b-9 induces smooth muscle cell (SMC) and
      endothelial cell (EC) activation and proliferation. All these data suggest that
      activation of the complement system plays an important role in atherogenesis.

PMID- 15258313
TI  - Structure of the Ly49 family of natural killer (NK) cell receptors and their
      interaction with MHC class I molecules.
AB  - Natural killer (NK) cells are an essential component of the innate immunity
      toward tumors and virally infected cells. The function of NK cells is regulated
      by a precise balance between inhibitory and activating signals. These signals are
      mediated by NK cell receptors that bind either classical MHC class I molecules or
      their structural relatives such as MICA, ULBP, RAE-1, and H-60. Two separate
      families of NK cell receptors have been identified: the immunoglobulin-like
      family (KIR, LIR) and C-type lectin-like family (Ly49, NKG2D, and CD94/NKG2).
      Here we summarize the structure of Ly49 C-type lectin-like proteins hitherto
      solved (Ly49A, Ly49C and Ly49I) and their interaction with MHC class I molecules
      as determined by the co-crystal structure of Ly49A/H-2Dd and Ly49C/H-2Kb.

PMID- 15258314
TI  - Assessment of a cellular vaccination approach consisting of crawling dendritic
      cells (CDCs) transduced with HSV-1-Deltapac vectors.
AB  - Crawling dendritic cells (CDCs) and herpes simplex virus-1 (HSV-1) amplicon
      vectors were utilized in this study: (1) to evaluate whether CDCs can be
      transduced by HSV-1 amplicon vectors; (2) to assess the effects of HSV-1
      infections on structure and functions of CDCs; (3) to assess the capabilities of
      the transduced CDC to express, process, and present the transgene products; and
      (4) to induce in vitro and in vivo priming of T cells and B cells. CDC supported
      amplicon-mediated transgene expression while retaining the ability to perform
      mixed lymphocyte reaction (MLR) and priming of naive T cells. Then it was tested
      whether transduced CDC were able to initiate immunity against either the amplicon
      particle and/or the product encoded by the delivered transgene by injecting
      groups of mice with transduced CDCs expressing GFP or LacZ. Spleen cells of these
      mice were stimulated by co-incubation with cells expressing: (1) either one of
      the transgenes (GFP or LacZ), (2) peptides of beta-gal, or (3) peptides of HSV-1
      glycoprotein B (gB). Interestingly, no significant cytotoxic T lymphocyte (CTL)
      activity against the transgenes or against gB was observed. In contrast, mice
      developed high levels of antibodies against gB and LacZ.Mainly, the findings that
      CDCs not only express amplicon-delivered transgene, but were able to induce MLR
      and priming of naive T cells against the transduced antigen, open up unexpected
      possibilities and the likelihood to use CDCs as a vehicle for cellular
      immunization against any transduced antigens. However, these results indicate
      that HSV-1 amplicon-transduced CDCs induce effective priming and a humoral
      response, but no strong cell-mediated immune response.

PMID- 15258312
TI  - The immune system in the elderly: activation-induced and damage-induced
      apoptosis.
AB  - Apoptosis is a complex cell-death process that allows cells to die in a
      controlled fashion. Our overall health relies to a great extent on the proper
      balance between the normal removal of damaged or unneeded cells via apoptosis and
      proliferation of the cells that comprise our body. Increasing evidence suggests
      that apoptosis is involved in many physiological processes and pathological
      conditions. It plays an important role during development, in maintaining tissue
      homeostasis, in responding to cellular damage, and in preventing neoplastic
      diseases. Apoptosis is a key regulator of clonotypic diversity generation during
      lymphocyte ontogenesis and is essential for the proper function of the immune
      system, controlling lymphocyte activation and clonal expansion following
      antigenic stimulation. There are various types of apoptosis, induced by different
      kinds of stimuli and in cells and tissues of different natures. On the basis of
      the nature of the apoptosis-inducing stimuli, two main apoptotic pathways can be
      identified: an activation-induced apoptosis, initiated by a variety of signals,
      such as the binding of ligands to their death-promoting receptors on the cell
      surface, and a damage-induced apoptosis, triggered by a damage to the nucleous or
      other cellular components. Apoptosis is markedly involved in many changes
      characteristic of immunosenescence, such as thymic involution, alteration of T
      cell repertoire, accumulation of memory/effector cells, and autoimmunity. The
      intense investigation of the age-related changes occurring in cell-death
      phenomena and on their precise impact on aging has resulted in controversial
      data. During senescence, the activation-induced and damage-induced apoptotic
      pathways could be differentially modulated, with variable impacts on the aging
      process. Changes in either of these two main apoptotic networks that may occur
      during aging could lead to disease. A correct modulation of apoptosis may be
      useful for prolonging the lifespan or at least reducing age-related degenerative
      and inflammatory pathologies and neoplastic diseases whose incidence increases
      with age. Careful study of literature together with personal experience in the
      field of senescence causes us to propose a new reading register that better
      explains and integrates many of the apparently discordant results.

PMID- 15258315
TI  - Mammalian sensitivity to elemental gold (Au degrees).
AB  - There is increasing documentation of allergic contact dermatitis and other
      effects from gold jewelry, gold dental restorations, and gold implants. These
      effects were especially pronounced among females wearing body-piercing gold
      objects. One estimate of the prevalence of gold allergy worldwide is 13%, as
      judged by patch tests with monovalent organogold salts. Eczema of the head and
      neck was the most common response of individuals hypersensitive to gold, and
      sensitivity can last for at least several years. Ingestion of beverages
      containing flake gold can result in allergic-type reactions similar to those seen
      in gold-allergic individuals exposed to gold through dermal contact and other
      routes. Studies with small laboratory mammals and injected doses of colloidal
      gold showed increased body temperatures, accumulations in reticular cells, and
      dose enhancement in tumor therapy; gold implants were associated with tissue
      injuries. It is proposed that Au degrees toxicity to mammals is associated, in
      part, with formation of the more reactive Au+ and Au3+ species.

PMID- 15258316
TI  - Plasma selenium decrease during pregnancy is associated with glucose intolerance.
AB  - There is an increased requirement for selenium during pregnancy, presumably for
      fetal growth, which manifests as decreasing maternal blood and tissue selenium
      concentrations. These decreases are greater in pregnant women with gestational or
      preexisting diabetes. We measured selenium status and glucose tolerance between
      wk 12 and 34 of gestation in 22 pregnant women. We found that the increase in
      blood glucose in response to an oral glucose challenge at 12 wk gestation and the
      increase in fasting glucose during pregnancy were inversely correlated with
      plasma selenium concentration. Women with lower plasma glutathione peroxidase
      activities during pregnancy also tended to have higher fasting glucose levels.
      These inverse relationships between selenium status and glucose tolerance are
      consistent with earlier observations that suggest a link between selenium and
      glucose metabolism. The observation that changes in serum glucose were not
      accompanied by changes in insulin suggests that selenium may affect glucose
      metabolism downstream from insulin, or through independent energy regulatory
      pathways such as thyroid hormone.

PMID- 15258317
TI  - Effect of zinc supplementation on hematological parameters in athletes.
AB  - The hematological effects of oral supplementation of zinc to training athletes
      are reported in the present study. A total of 30 subjects between 16 and 22 yr of
      age volunteered to participate in a 4-wk study. They were equally divided into
      three groups. Group 1 acted as resting controls receiving daily doses of 3 mg
      Zn/kg body wt. Group 2 was actively engaged in wrestling and exercised for 90-120
      min, 5 d a week. Group 3 was also actively engaged in wrestling and exercised for
      90-120 min, 5 d a week, but they were supplemented with 3 mg Zn/kg body wt per
      day. The erythrocyte, leukocyte, and thrombocyte counts and the hemoglobin values
      of all subjects participating in the study were measured before and after
      exercise at the beginning and at the end of the 4-wk study period. In all groups,
      there were no significant differences in the measured parameters before and after
      exercise. At the end of the supplementation period, the parameters of the
      subjects in groups 1 and 3 were significantly higher than those of group 2, both
      before (p<0.005) and after (p<0.05) exercise. These results suggest that zinc
      supplementation has a positive effect on hematological parameters in athletes.

PMID- 15258318
TI  - Effect of arsenic (AsIII) on glutathione-dependent enzymes in liver and kidney of
      the freshwater fish Channa punctatus.
AB  - The possible role of glutathione-dependent enzymes in the liver and kidney of the
      freshwater fish Channa punctatus has been studied after exposure to arsenic
      trioxide for different durations. Activities of glutathione-S-transferases,
      glutathione peroxidase, glutathione reductase, and catalase decreased in the
      liver and kidney as a result of the initial increase in arsenic concentration in
      the liver and kidney. However, during longer exposures, a decline in arsenic
      concentration corresponded with improved enzyme activity. Because arsenic
      manifests its toxicity by inducing oxidative stress, the antioxidant enzymes,
      especially the glutathione-dependent enzymes, play a protective role in arsenic
      toxicity.

PMID- 15258319
TI  - Airborne manganese exposure differentially affects end points of oxidative stress
      in an age- and sex-dependent manner.
AB  - Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese
      in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or
      manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We
      assessed biochemical end points indicative of oxidative stress in five brain
      regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum.
      Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA
      levels, and total glutathione (GSH) levels were determined for all five regions.
      Although most brain regions in the three groups of animals were unaffected by
      manganese exposure in terms of GS protein levels, there was significantly
      increased protein (p<0.05) in the hippocampus and decreased protein in the
      hypothalamus of young male rats exposed to manganese phosphate as well as in the
      aged rats exposed to 0.1 mg/m3 MnSO4. Conversely, GS protein was elevated in the
      olfactory bulb of females exposed to the high dose of MnSO4. Statistically
      significant decreases (p<0.05) in MT and GS mRNA as a result of manganese
      exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the
      young male rats, in the hypothalamus in the young female rats, and in the
      hippocampus in the senescent males. Total GSH levels significantly (p<0.05)
      decreased in the olfactory bulb of manganese exposed young male rats and
      increased in the olfactory bulb of female rats exposed to manganese. Both the
      aged and young female rats had significantly decreased (p<0.05) GSH in the
      striatum resulting from manganese inhalation. The old male rats also had depleted
      GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3
      manganese phosphate exposure. These results demonstrate that age and sex are
      variables that must be considered when assessing the neurotoxicity of manganese.

PMID- 15258320
TI  - Zinc sulfate in the prevention of total-body irradiation-induced early
      hematopoietic toxicity: a controlled study in a rat model.
AB  - Exposure to ionizing total-body radiation suppresses hematopoiesis, resulting in
      decreased production of blood cells. Many researchers have demonstrated the
      critical role of zinc (Zn) in diverse physiological processes, such as growth and
      development, maintenance and priming of the immune system, and tissue repair. The
      aim of the present study was to determine the effects of zinc sulfate (40 mg/kg
      and 80 mg/kg) on early hematopoietic toxicity, caused by total-body irradiation
      (TBI) of rats with a single dose of 8 Gy. Both in the Zn 40 and in the Zn 80
      groups, there were significantly increased white blood cell (WBC) count, when
      compared with control group. The WBC count was higher in the control group than
      in the TBI group. This result was statistically significant (p<0.05). Both the
      TBI+Zn 40 and the TBI+Zn 80 groups had a significantly protected WBC count
      against TBI. No difference was detected in any final measurement of thrombocyte
      count and hemoglobin level with direct comparison among all groups, with the
      exception that the hemoglobin level in the Zn 80 group compared to the control
      group. Whereas hemoglobin level in the control group was at a median figure of
      13.98 g/dL (13.30-14.80), it was at a median figure of 14.25 g/dL (14.10-15.50)
      in the Zn 80 group. It would be worthwhile studying the effect of oral zinc
      sulfate supplements in radiation-treated cancer patients, in the hope of reducing
      radiation-induced toxicity.

PMID- 15258310
TI  - Mucosal immunity: overcoming the barrier for induction of proximal responses.
AB  - Vaccination represents one of the most efficacious and cost-effective medical
      interventions. It is the only medical intervention proven to eliminate disease at
      a global level. Many of the pathogens against which we most require adequate
      vaccines infect via the highly exposed mucosal surfaces. For this reason the
      mucosa is often considered the first, and sometimes only, line of defense.
      Therefore, responses that protect the local mucosa are vital. In this review, we
      first explore the immunological mechanisms that protect the mucosa. We then
      review the literature of mucosal vaccines within the principles of antigenic
      composition, dose, and danger, highlighting the need and niche for the next
      generation of mucosal vaccines.

PMID- 15258321
TI  - Levels of lipid peroxidation, superoxide dismutase, and Na+/K+ ATPase in some
      tissues of rats exposed to a Nigerian-like diet and cadmium.
AB  - The purpose of the present study was to examine the role of a wholly compounded
      Nigerian-like diet on the activities of superoxide dismutase (SOD) and Na+/K+
      ATPase and level of lipid peroxidation in oral cadmium toxicity. Nine-week-old
      Wistar albino rats (100 +/- 2.0 g) were exposed to 100 ppm cadmium in drinking
      water and the Nigerian-like diet (low in protein and high in carbohydrates and
      fiber) for 16 wk. The results obtained indicate that cadmium reduced weight gain
      and increased fecal output of rats, which was further potentiated by the Nigerian
      like diet. Cadmium was concentrated in the intestine, liver, and kidney, with the
      highest level observed in the kidney, followed by the liver. The Nigerian-like
      diet reduced the concentration of cadmium in these tissues. Cadmium increased
      lipid peroxidation and inhibited SOD and Na+/K+ ATPase in the tissues. These were
      also aggravated in rats fed the Nigerian-like diet. Because the Nigerian-like
      diet increased lipid peroxidation and inhibited SOD and Na+/K+ ATPase in the
      tissues, it rendered rats more susceptible to cadmium toxicity.

PMID- 15258322
TI  - Validation of method for total selenium determination in yeast by flame atomic
      absorption spectrometry.
AB  - A procedure using open digestion followed by flame atomic absorption spectrometry
      is described for measuring the total selenium content of Se-enriched yeast. The
      limits of detection and quantitation were 2.5 mg/L and 5 mg/L Se, respectively.
      The signal response was linear over the range of 5-50 mg/L Se, and the average
      recovery from spiked samples was 98.9%. The validated method was used to measure
      the Se content of Se-enriched yeast reference material and produced a result of
      2145 +/- 38 mg/kg (n = 3), which is in good agreement with the certified level of
      2125 +/- 65 mg/kg.

PMID- 15258323
TI  - Positive correlation between plasma concentrations in copper and leptin in
      healthy Kuwatis.

PMID- 15258324
TI  - HAART in India: heartening prospects & disheartening problems.

PMID- 15258325
TI  - Disturbances of haemostasis in diabetes mellitus.
AB  - Diabetes mellitus is associated with disturbances in haemostasis that could
      contribute to the development of thrombotic complications.The present study was
      undertaken to determine the behavior of coagulation variables and fibrinolytic
      system in diabetes mellitus. Forty five diabetic patients and forty five matched
      controls were evaluated by doing the following haemostatic parameter, prothrombin
      time, partial thromboplastin time, thrombin time, coagulation factors assay II,
      VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, alpha2
      antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of
      fibrinogen, alpha2- antiplasmin, & PAI and lower level of protein C. Other
      haemostatic parameters did not show statistically significant difference between
      diabetic patients and control group. Significantly elevated levels of PAI, alpha2
      antiplasmin together with low protein C level in diabetic patients may result in
      the disturbance of haemostatic balance favoring thrombotic events. CONCLUSION:
      High levels of plasma fibrinogen, alpha2A- antiplasmin with low plasma protein C
      activity could lead to a prothrombotic tendency in insulin dependent diabetic
      patients. Moreover, in non-insulin dependent diabetic patients, the above
      mentioned parameters together with high levels of ADP-induced platelet
      aggregation and plasminogen activator inhibitor may increase the risk of
      thrombotic complications. Obesity can be considered as an additional risk factor
      for development of thrombosis in diabetic patients.

PMID- 15258326
TI  - GSTT1 gene deletion is associated with lung cancer in Mexican patients.
AB  - Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in
      the deactivation of carcinogens, several tobacco-derived carcinogens, and
      xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus,
      deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null
      genotype) may play a role in the induction of lung cancer by smoking. We studied
      the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178
      healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung
      cancer patients. Comparisons between groups showed that there was an increased
      lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients
      showed significant differences when compared with controls: nonsmokers, passive
      smokers, and smokers. Twenty-one percent of lung cancer patients carried the
      deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among
      passive smokers, and 5% among smokers. Thus, there is a significant association
      between this genotype and the possibility to risk of developing lung cancer.

PMID- 15258327
TI  - Clinical interest of the combined use of serum CD26 and alpha-L-fucosidase in the
      early diagnosis of colorectal cancer.
AB  - The purpose of this study was to assess if the combination of CD26 and alpha-L
      fucosidase has a role in the diagnosis of colorectal cancer, paying particular
      attention to the stages in which the tumour is not yet disseminated. CD26
      concentration and alpha-L-fucosidase activity were determined in sera from 110
      colorectal cancer patients and 46 donors. The combination of CD26 and alpha-L
      fucosidase showed a specificity of 100% with a sensitivity of 64% in the
      diagnosis of colorectal cancer. Interestingly, the combination of both markers
      had a sensitivity of 75% in the stage I at the highest specificity (100%),
      providing also high sensitivity levels for the other non-disseminated stages (66%
      for stages II and III). In conclusion, the combined use of CD26 and alpha-L
      fucosidase offers high sensitivity with high specificity in the diagnosis of
      colorectal cancer, especially at the earliest stage (TNM I).

PMID- 15258328
TI  - Receiver operating characteristic (ROC) to determine cut-off points of biomarkers
      in lung cancer patients.
AB  - The role of biomarkers in disease prognosis continues to be an important
      investigation in many cancer studies. In order for these biomarkers to have
      practical application in clinical decision making regarding patient treatment and
      follow-up, it is common to dichotomize patients into those with low vs. high
      expression levels. In this study, receiver operating characteristic (ROC) curves,
      area under the curve (AUC) of the ROC, sensitivity, specificity, as well as
      likelihood ratios were calculated to determine levels of growth factor biomarkers
      that best differentiate lung cancer cases versus control subjects. Selected cut
      off points for p185(erbB-2) and EGFR membrane appear to have good discriminating
      power to differentiate control tissues versus uninvolved tissues from patients
      with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at
      least 90% for selected cut-off points for p185(erbB-2) membrane, EGFR membrane,
      and FASE when comparing between control versus carcinoma tissues from lung cancer
      cases. Using data from control subjects compared to patients with lung cancer, we
      presented a simple and intuitive approach to determine dichotomized levels of
      biomarkers and validated the value of these biomarkers as surrogate endpoints for
      cancer outcome.

PMID- 15258330
TI  - Utility of free/total prostate specific antigen (f/t PSA) ratio in diagnosis of
      prostate carcinoma.
AB  - The discovery that PSA exists in serum in both free and complexed forms led to
      development of immunoassays specific for different PSA forms. This helped in
      measuring free PSA in the presence of PSA-ACT (PSA-alpha antichymotrypsin), hence
      it was possible to calculate the percent free PSA or free to total PSA ratio,
      measurement of which was helpful in reducing the number of unnecessary biopsies
      significantly, while maintaining a high clinical sensitivity for detection of
      cancer. The study was performed on 103 consecutive male patients (mean age 68 +/-
      10.8 years SD) comprising of 90 patients with benign disease (87%) and 13
      prostate carcinoma patients (13%), who had histologically proven prostate cancer.
      Patients with total PSA between 2-25 ng/ml were included in the study. 30 normal
      healthy males with age 58 +/- 10 years, served as control. Serum total PSA and
      free PSA were analyzed using streptavidin biotin EIA method (M/s Roche
      Diagnostics, Germany). The mean total PSA in normal healthy control subjects was
      1.86 +/- 1.07 ng/ml. It was increased significantly in diseased condition. Its
      mean concentration in carcinoma patients was 12.6 +/- 5.3 ng/ml and in benign
      patients it was 6.3 +/- 4.6 ng/ml. The free to total PSA ratio in all the three
      groups was significantly different (p < 0.004) from each other. In carcinoma
      patients, mean f/t PSA ratio was 0.12 +/- 0.06 as compared to 0.21 +/- 0.11 and
      0.28 +/- 0.17 in benign patients and in control respectively. The sensitivity and
      specificity of the test was calculated at different f/t PSA ratio cutoff. At 0.1
      cutoff value, sensitivity of the test was 54% and specificity was 83%. The
      positive predictive value (ppv) was 32% and negative predictive value (npv) was
      92%. From cutoff value of 0.12 to 0.16, sensitivity was increased from 54% to 85%
      but specificity was reduced from 78% to 67%. The ppv did not show much change and
      npv was increased from 92% to 97%. Increasing the cut off value thereafter showed
      no change in sensitivity but specificity was further reduced to 40%, therefore in
      this patient series, f/t PSA ratio cutoff of 0.16 was found to be the appropriate
      cutoff value. Combination of this ratio cutoff with other parameters like serum
      total PSA, DRE and TRUS helped in increasing the sensitivity of the test and this
      also helped in reducing the number of unnecessary biopsies. In 103 men who were
      biopsied, 13 (12.6%) prostatic carcinoma were identified. Among these 13 cancer
      patients, 9 patients had abnormal findings in DRE.7 individuals out of these 9,
      also had free to total PSA ratio lower than 0.16 and would have been biopsied and
      diagnosed anyway. If we use only f/t PSA ratio less than 0.16, to decide whom to
      biopsy, we would have biopsied and diagnosed 11/13 cases i.e. sensitivity of 85%
      but If we decide to biopsy those patients who had abnormal DRE and those who had
      low f/t PSA ratio, we could identify 13/13 carcinoma i.e. 100% sensitivity.
      Combining the f/t PSA ratio with total PSA, DRE and TRUS findings could help in
      reducing the number of unnecessary biopsies. 37 patients who were negative for
      malignancy having total PSA in the range of 5-20 ng/ml, normal DRE and TRUS
      findings, have been biopsied but with combination of total PSA in the range of 5
      20 ng/ml, normal findings in digital rectal examination and TRUS and f/t PSA
      ratio more than 0.16 (cutoff), we could have avoided 16 biopsies which were
      unnecessary that means there was 43% reduction in unnecessary biopsies.

PMID- 15258329
TI  - Cervical acid phosphatase: a biomarker of cervical dysplasia and a potential
      surrogate endpoint for colposcopy.
AB  - BACKGROUND: In 2000, cervical acid phosphatase (CAP) has been recently described
      as a biomarker labeling abnormal squamous cells on Pap smears (USPTO #6,143,512).
      The enzyme activity is presented as a red, granular deposit on a modified
      Papanicolaou background. This unique property was utilized for development of
      MarkPap technology intended for cervical cancer screening. MATERIAL/PATIENTS &
      METHODS: We conduct a multicenter, random assignment, assessor blinded, 2-group
      (test and control), split-sample designed clinical trial on 1,500
      subject/specimens to assess safety and efficacy of the new test, in comparison
      with the control, for cervical cancer screening in standard Pap test environment.
      Safety is measured with frequency, severity and relation of adverse events.
      Efficacy is measured with primary endpoints (portion of positive/abnormal
      specimens detected, and the false negative rate). At the end of the follow-up
      period (two years) when the study will be completed, other efficacy endpoints
      such as accuracy (sensitivity/specificity) and predictive values will be added to
      the method evaluation. Here we present in interim analysis. RESULTS: In April
      2003, the recruitment was completed and the first twelve hundred cases have been
      evaluated. There was no serious or related adverse event in both groups. Minor,
      unrelated adverse events were rare and insignificantly distributed in both
      groups. PRIMARY ENDPOINTS: A: Portion of positive/abnormal specimens detected: Pe
      (new test) = 0.166, Ps (Pap control): 0.082; Ps' (ACS reported value for US in
      year 2000): 0.07. Pe >/= Ps + delta, for delta = 0.5Ps. B. False negative rate:
      Pe = 0.05, Ps' = 0.10. Confidence intervals: 95% CI: Test [0.148-0.193], Pap
      control [0.068-0.098]. OR = 2.26. chi2 = 40.69101 is greater than the critical
      value of 3.841 (P < 0.01). CONCLUSION: We concluded that CAP had added to
      visibility of Pap test and has enabled cytoscreeners to significantly improve the
      detection of positive/abnormal specimens and reduce false negative rate. We
      discuss this unique property of CAP with emphasis on using it as a surrogate
      endpoint for colposcopy and eventual removal of a cervical lesion that, if
      untreated, could progress into cancer.

PMID- 15258331
TI  - Proteomics in diagnostics.

PMID- 15258332
TI  - The use of urine proteomic and metabonomic patterns for the diagnosis of
      interstitial cystitis and bacterial cystitis.
AB  - The advent of systems biology approaches that have stemmed from the sequencing of
      the human genome has led to the search for new methods to diagnose diseases.
      While much effort has been focused on the identification of disease-specific
      biomarkers, recent efforts are underway toward the use of proteomic and
      metabonomic patterns to indicate disease. We have developed and contrasted the
      use of both proteomic and metabonomic patterns in urine for the detection of
      interstitial cystitis (IC). The methodology relies on advanced bioinformatics to
      scrutinize information contained within mass spectrometry (MS) and high
      resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to
      distinguish IC-affected from non-affected individuals as well as those suffering
      from bacterial cystitis (BC). We have applied a novel pattern recognition tool
      that employs an unsupervised system (self-organizing-type cluster mapping) as a
      fitness test for a supervised system (a genetic algorithm). With this approach, a
      training set comprised of mass spectra and 1H-NMR spectra from urine derived from
      either unaffected individuals or patients with IC is employed so that the most
      fit combination of relative, normalized intensity features defined at precise m/z
      or chemical shift values plotted in n-space can reliably distinguish the cohorts
      used in training. Using this bioinformatic approach, we were able to discriminate
      spectral patterns associated with IC-affected, BC-affected, and unaffected
      patients with a success rate of approximately 84%.

PMID- 15258333
TI  - Serum protein expression profiling for cancer detection: validation of a SELDI
      based approach for prostate cancer.
AB  - Multiple studies have reported that analysis of serum and other bodily fluids
      using surface enhanced laser desorption/ionization time of flight mass
      spectroscopy (SELDI-TOF-MS) can identify a "fingerprint" or "signature" of
      spectral peaks that can separate patients with a specific disease from normal
      control patients. Ultimately, classification by SELDI-TOF-MS relies on spectral
      differences in position and amplitude of resolved peaks. Since the
      reproducibility of quantitation, resolution and mass accuracy of the SELDI-TOF
      MS, or any high throughput mass spectrometric technique, has never been
      determined this method has come under some skepticism as to its clinical
      usefulness. This manuscript describes a detailed design of a three-phase study to
      validate the clinical usefulness of SELDI-TOF-MS in the identification of
      patients with prostatic adenocarcinoma (PCA). At the end of this validation
      study, the usefulness of the general SELDI-TOF-MS approach to identifying
      patients with PCA will be demonstrated and how it compares with PCA diagnosis by
      measuring prostate specific antigen.

PMID- 15258334
TI  - Novel approaches to visualization and data mining reveals diagnostic information
      in the low amplitude region of serum mass spectra from ovarian cancer patients.
AB  - The ability to identify patterns of diagnostic signatures in proteomic data
      generated by high throughput mass spectrometry (MS) based serum analysis has
      recently generated much excitement and interest from the scientific community.
      These data sets can be very large, with high-resolution MS instrumentation
      producing 1-2 million data points per sample. Approaches to analyze mass spectral
      data using unsupervised and supervised data mining operations would greatly
      benefit from tools that effectively allow for data reduction without losing
      important diagnostic information. In the past, investigators have proposed
      approaches where data reduction is performed by a priori "peak picking" and
      alignment/warping/smoothing components using rule-based signal-to-noise
      measurements. Unfortunately, while this type of system has been employed for gene
      microarray analysis, it is unclear whether it will be effective in the analysis
      of mass spectral data, which unlike microarray data, is comprised of continuous
      measurement operations. Moreover, it is unclear where true signal begins and
      noise ends. Therefore, we have developed an approach to MS data analysis using
      new types of data visualization and mining operations in which data reduction is
      accomplished by culling via the intensity of the peaks themselves instead of by
      location. Applying this new analysis method on a large study set of high
      resolution mass spectra from healthy and ovarian cancer patients, shows that all
      of the diagnostic information is contained within the very lowest amplitude
      regions of the mass spectra. This region can then be selected and studied to
      identify the exact location and amplitude of the diagnostic biomarkers.

PMID- 15258335
TI  - Diagnostic proteomics: serum proteomic patterns for the detection of early stage
      cancers.
AB  - The ability to interrogate thousands of proteins found in complex biological
      samples using proteomic technologies has brought the hope of discovering novel
      disease-specific biomarkers. While most proteomic technologies used to discover
      diagnostic biomarkers are quite sophisticated, "proteomic pattern analysis" has
      emerged as a simple, yet potentially revolutionary, method for the early
      diagnosis of diseases. Utilizing this technology, hundreds of clinical samples
      can be analyzed per day and several preliminary studies suggest proteomic pattern
      analysis has the potential to be a novel, highly sensitive diagnostic tool for
      the early detection of cancer.

PMID- 15258336
TI  - Characterization of plasma membrane proteins from ovarian cancer cells using mass
      spectrometry.
AB  - To determine how the repertoire of plasma membrane proteins change with disease
      state, specifically related to cancer, several methods for preparation of plasma
      membrane proteins were evaluated. Cultured cells derived from stage IV ovarian
      tumors were grown to 90% confluence and harvested in buffer containing CHAPS
      detergent. This preparation was centrifuged at low speed to remove insoluble
      cellular debris resulting in a crude homogenate. Glycosylated proteins in the
      crude homogenate were selectively enriched using lectin affinity chromatography.
      The crude homogenate and the lectin purified sample were prepared for mass
      spectrometric evaluation. The general procedure for protein identification began
      with trypsin digestion of protein fractions followed by separation by reversed
      phase liquid chromatography that was coupled directly to a conventional tandem
      mass spectrometer (i.e. LCQ ion trap). Mass and fragmentation data for the
      peptides were searched against a human proteome data base using the informatics
      program SEQUEST. Using this procedure 398 proteins were identified with high
      confidence, including receptors, membrane-associated ligands, proteases,
      phosphatases, as well as structural and adhesion proteins. Results indicate that
      lectin chromatography provides a select subset of proteins and that the number
      and quality of the identifications improve as does the confidence of the protein
      identifications for this subset. These results represent the first step in
      development of methods to separate and successfully identify plasma membrane
      proteins from advanced ovarian cancer cells. Further characterization of plasma
      membrane proteins will contribute to our understanding of the mechanisms
      underlying progression of this deadly disease and may lead to new targeted
      interventions as well as new biomarkers for diagnosis.

PMID- 15258337
TI  - SELDI-TOF serum profiling for prognostic and diagnostic classification of breast
      cancers.
AB  - Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass
      spectrometry has emerged as a successful tool for serum based detection and
      differentiation of many cancer types, including breast cancers. In this study, we
      have applied the SELDI technology to evaluate three potential applications that
      could extend the effectiveness of established procedures and biomarkers used for
      prognostication of breast cancers. Paired serum samples obtained from women with
      breast cancers prior to surgery and post-surgery (6-9 mos.) were examined. In
      14/16 post-treatment patients, serum protein profiles could be used to
      distinguish these samples from the pre-treatment cancer samples. When compared to
      serum samples from normal healthy women, 11 of these post-treatment samples
      retained global protein profiles not found in healthy women, including five low
      mass proteins that remained elevated in both pre-treatment and post-treatment
      serum groups. In another pilot study, serum profiles were compared for a group of
      30 women who were known BRCA-1 mutation carriers, half of whom subsequently
      developed breast cancer within three years of the sample procurement. SELDI
      protein profiling accurately classified 13/15 women with BRCA-1 breast cancers
      from the 15 non-cancer BRCA-1 carriers. Additionally, the ability of SELDI to
      distinguish between the serum profiles from sentinel lymph node positive and
      sentinel lymph node negative patients was evaluated. In sentinel lymph node
      positive samples, 22/27 samples were correctly classified, in comparison to the
      correct classification of 55/71 sentinel lymph node negative samples. These
      initial results indicate the utility of protein profiling approaches for
      developing new diagnostic and prognostic assays for breast cancers.

PMID- 15258338
TI  - Foreword: 12th European Conference On Clinical Hemorheology, Sofia, Bulgaria,
      June 22-26, 2003 eurosummer school on biorheology, Varna, Bulgaria, June 29-30,
      2003.

PMID- 15258339
TI  - From hyperviscosity to endothelial dysfunction: a return trip?

PMID- 15258340
TI  - Hemorheology and vascular control mechanisms.
AB  - Blood rheology is a well-known determinant of tissue perfusion and, according to
      the Poiseuille relation, hemodynamic resistance in a constant-geometry vascular
      network is directly proportional to blood viscosity. However, this direct
      relationship cannot be observed in all in vivo studies. Further, there are
      several reports indicating marked differences between the in vivo and ex vivo
      flow properties of blood. These differences can be explained, in large part, by
      considering special hemorheological mechanisms (e.g., Fahraeus-Lindqvist effect,
      axial migration) that are of importance in the microcirculation. Additionally,
      the influence of altered rheological properties of blood and its components on
      vascular control mechanisms requires consideration: (1) There is an indirect
      relation between blood rheology and microvascular tone that is mediated by tissue
      oxygenation, with a compensatory vasodilation occurring if tissue perfusion is
      impaired due to hemorheological deterioration; (2) Blood rheology may influence
      vascular tone through alterations of wall shear stress, which in turn determines
      endothelial generation of vasoactive substances (e.g., nitric oxide). This latter
      point is of particular relevance to the field of clinical hemorheology, since
      enhanced red blood cell aggregation has been shown to affect nitric oxide
      synthesis and thus control of vascular smooth muscle tone. Such multiple pathways
      by which hemorheological changes can affect vascular resistance help to explain
      the continuing difficulty of predicting correlations between in vivo and ex vivo
      hemorheological behavior; they also suggest the need for continued experimental
      studies in this area.

PMID- 15258341
TI  - Basic factors determining the hemorheological disorders in the microcirculation.
AB  - Hemorheological properties and disorders are very specific in the
      microcirculation since blood is actually not a fluid in the capillaries and in
      the adjacent arterioles and venules. This is because almost half of the blood
      volume constitutes the red and white blood cells whose size is commensurable with
      the microvessels lumen. Based on perennial investigations we concluded that the
      advancement of blood in capillaries is primarily dependent on the "structure" of
      the flowing blood that determines the resistance to blood advancement in the
      microvessels rather than on the well-known hydrodynamic relationships
      characteristic for the larger blood vessels. Basing on the perennial research of
      the hemorheological disorders in the microvessels we succeeded to specify the
      principal factors determining the blood flow resistance in the microcirculation.
      These factors are as follows: the erythrocyte enhanced aggregability > their
      deformability > the local hematocrit > the blood plasma viscosity. Solution of
      these theoretical problems is very important for the theory and practical
      medicine, since the blood rheological disorders in the microcirculation play a
      significant role in development and outcome of such essential diseases as the
      cerebral and cardiac infarcts, the diabetus mellitus, arterial hypertension,
      tumor grow, and many others.

PMID- 15258342
TI  - Erythrocytes and platelet adhesion to endothelium are mediated by specialized
      molecules.
AB  - Erythrocytes in normal conditions have weak interactions with other blood cells
      and endothelial cells while in pathological circumstances they can adhere to
      endothelium and aggregate or agglutinate to blood cells. Erythrocyte adhesion was
      found to be abnormal in sickle cell anemia and diabetes mellitus and correlated
      to the vascular complications. Further studies demonstrated that VLA-4 adhesion
      molecule (alpha4beta1) present on erythrocytes bound to vascular cell adhesion
      molecule (VCAM-1) of the endothelium. In addition, the blood group Lutheran
      molecule (LU) overexpressed on sickle erythrocytes bind to laminin present on
      cells or in the intercellular space. In diabetes mellitus the formation of
      advanced glycation end products (AGE) by reaction between carbohydrates and free
      aminogroups of lysine is responsible for red blood cell membrane glycation. AGEs
      present on RBCs bind to the receptor for AGE (RAGE) on endothelium, activating
      endothelial cells. A molecule related to blood group Rhesus was demonstrated to
      belong to the intercellular adhesion molecule (ICAM) family. ICAM-4 binds to
      integrins present on leukocytes (CD11-CD18) and on platelets (alpha2beta4)
      offering a surface, which can be involved in thrombosis. The identification of
      erythrocytes adhesion molecules open a new way to understand thrombotic processes
      and vascular dysfunction.

PMID- 15258343
TI  - From hemorheology to vascular mechanobiology: An overview.
AB  - Almost all of the cells of the human body are subjected to mechanical stresses.
      In endothelial cells, mechanical stresses can vary from some milli-Pascal (shear
      stress) to one ore more Pascal (hydrostatic pressure). Now it is know that
      mechanical stresses have a decisive part cellular physiology. However, if the
      main biological effects of mechanical stress are well related, the mechanisms
      allowed the relation between mechanical stress to physiological phenomenon remain
      nearly unknown (mechanotransduction phenomenon). In this work, through personal
      results and published works, the authors considers all the effects of mechanical
      stresses and the possible hypothesis.

PMID- 15258344
TI  - Hemorheological aspects of the metabolic syndrome: markers of insulin resistance,
      obesity or hyperinsulinemia?
AB  - The metabolic syndrome is a major health problem in western countries, due to the
      deleterious metabolic consequences of sedentarity and rich diet in the large part
      of the population who exhibits the so-called "thrifty phenotype". This syndrome,
      which is at high risk for diabetes and atherothrombosis is associated with
      hemorheologic abnormalities. Initially, insulin resistance was considered as the
      core of the syndrome. However, it becomes clear that the syndrome is a cluster in
      which the combined effects of obesity, insulin resistance, and hyperinsulinemia
      can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects
      (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the
      respective importance of each of these factors. Subjects were divided in 6 groups
      according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured
      with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4),
      highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that
      whole blood viscosity at high shear rate is higher in obese subjects (p<0.01).
      Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012
      (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper
      quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect
      of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The
      aggregability index "M1" is increased when SI<1.1 in both obese and nonobese
      subjects. No clear effect of either SI or obesity on hematocrit is observed. On
      the whole, obesity and insulin resistance both impair blood rheology by acting on
      red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate
      reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is
      rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the
      metabolic syndrome is far to be only a reflect of insulin resistance alone.

PMID- 15258345
TI  - Hemorheological disturbances in the overtraining syndrome.
AB  - Contemporary sports imply huge training volumes, with thus an increasing danger
      of overloading. The timely detection of the state of overloading in the organism
      as a whole or in skeletal muscles presents a difficult and complicated problem. A
      standardized questionnaire has been proposed by the French consensus group on
      overtraining of the Societe Francaise de Medecine du Sport (SFMS) and allows the
      calculation of a "score" that may help to quantify the early clinical symptoms of
      the overtraining syndrome in sportsmen submitted to a heavy training program. We
      previously reported that this overtraining score is correlated with blood
      viscosity due to a correlation of this score with plasma viscosity and
      hematocrit. When subjects with a high score were compared to subjects with a
      lower score they appeared to have a higher blood viscosity at native (but not
      corrected) hematocrit, explained by higher values in both plasma viscosity and
      hematocrit. By contrast, there was no difference in RBC deformability and
      aggregation. Therefore, the early signs of overtraining in elite sportsmen are
      associated with a hemorheologic pattern that suggests some degree of reversal of
      the "autohemodilution" which characterizes fitness. In a further study we
      reported that the feeling of heavy legs in overtrained athletes is related to
      impaired hemorheology. Although well matched with controls for age and body
      composition, subjects with a complaint of heavy legs had higher plasma viscosity
      and a higher red cell aggregation as measured with laser backscattering. These
      findings suggest that the feeling of heavy legs in overtrained athletes are
      related to hemorheologic disturbances. In the light of the recent concept
      explaining this syndrome by a mild chronic inflammatory reaction, the
      investigation of hemorheology in overtraining can be a promising area for
      hemorheologists, providing both markers and likely pathophysiological
      explanations for some symptoms of this situation.

PMID- 15258346
TI  - Hemorheological disturbances as a marker of diabetic foot syndrome deterioration.
AB  - Diabetes mellitus is associated with vascular abnormalities. Hemorheological
      variables as well as the transcutaneous oxygen pressure (TcPO2) were measured in
      38 diabetic patients with critical limb ischemia to assess whether these
      variables could be of value to follow the deterioration in foot disease. Patients
      with previous history of foot ulcers or frank ulcers on presentation were
      followed for foot care. After a 12-month follow-up, they were divided into 2
      subgroups based on the regression of foot disease: 30% of patients improved foot
      ischemia, i.e., healed or improved ulcer, while the remainder 70% deteriorated,
      i.e., impaired ulcer or underwent an amputation. RBC aggregation, plasma
      viscosity and fibrinogen level observed at baseline visit, were significantly
      higher in the patients who deteriorated. Blood viscosity values at both shear
      rates high and low were not significantly different between the 2 subgroups.
      TcPO2 was significantly lower in patients who deteriorated compared with those
      who improved. With regard to prognostic values, RBC aggregation parameters and
      fibrinogen level offered the highest positive predictive values (of 89%, 94%, and
      88% respectively), comparable to that associated with TcPO2 (94%). Further
      analyses showed that combining markers of hemorheology with TcPO2 especially when
      TcPO2 value is in the range of 10-30 mmHg, may improve prognostic value for the
      management of the diabetic foot disease.

PMID- 15258347
TI  - Improving thrombolysis with encapsulated plasminogen activators and clinical
      relevance to myocardial infarction and stroke.
AB  - Our efforts have focused on investigating the potential benefit of encapsulated
      thrombolytic agents for treatment of clot-based crises. Liposome encapsulated
      plasminogen activators (LEPAs) have demonstrated improved thrombolysis in vivo in
      multiple laboratories. Compared to free agents, LEPAs demonstrate faster
      reperfusion times, reduced residual clot masses, and more rapid and complete
      restoration of blood flow. We have encapsulated streptokinase in both liposomes
      (LESK) and polymer microcapsules (MESK). Both formulations demonstrated
      reductions in reperfusion times, residual clot mass, and improved return of flow
      compared to identical dosages of free streptokinase in a thrombosed rabbit
      carotid, with MESK resulting in comparable or even greater improvements. In
      addition, marked reductions in bleeding complications and ventricular infarct
      size have been observed in a canine model of acute myocardial infarction. The
      mechanism for MESK has recently been explored in our laboratory using multiple
      microscopic techniques. MESK appears to resist adsorption to the leading edge of
      the thrombus, a common limitation for the permeation of free plasminogen
      activators. By avoiding adsorption and penetrating the thrombus, greater spatial
      distribution of the agent within the clot can be achieved. This data suggests
      that encapsulation of streptokinase could provide a therapeutic option for
      treatment of thrombosed arteries.

PMID- 15258348
TI  - Polymorphonuclear leukocyte: rheology, metabolism and integrin pattern in
      vascular atherosclerotic disease and in type 2 diabetes mellitus.
AB  - Leukocytes, and in particular polymorphonuclear cells (PMN), play a role in the
      organ injury that characterizes the progression of vascular atherosclerotic
      disease (VAD) and diabetes mellitus (DM). We enrolled subjects with VAD, subjects
      with type 2 DM (DM2) and subjects with VAD and DM2. We evaluated the initial
      relative flow rate (IRFR) of PMN, using the St. George Filtrometer, the PMN
      membrane fluidity, labelling intact PMN cells with the fluorescent probe 1.4
      (trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH), the PMN cytosolic Ca2+
      content marking the cells with the fluorescent probe Fura 2-AM and the PMN
      integrin profile using the flow cytofluorimetry. All these evaluations were
      effected at baseline and after activation with 4-phorbol-12-myristate-13-acetate
      (PMA). At baseline and after activation the IRFR did not distinguish normal
      subjects from any group of patients. The PMN membrane fluidity at baseline
      differentiated only normal from DM2 subjects, while after activation no
      significant variation of this parameter was observed in normal, VAD, DM2 and VAD
      DM2 subjects. The PMN cytosolic Ca2+ content, at baseline, discriminated only
      normal from VAD subjects with DM2, while after activation a significant increase
      of this parameter was evident in DM2 subjects and in VAD subjects with DM2.
      Regarding the PMN integrin pattern we observed, at baseline and after activation,
      a complex and non-univocal behaviour. In conclusion, the PMN rheological and
      metabolic pattern found in these groups of patients showed only small functional
      alterations while the integrin pattern was significantly different from that of
      normal subjects and added specific elements which may have potential
      therapeutical implications.

PMID- 15258349
TI  - Measurement of platelet aggregation during antiplatelet therapy in ischemic
      stroke.
AB  - Aspirin, ticlopidine and clopidogrel are used as a pharmacological means to
      efficiently decrease the number of reoccurrence of ischemic stroke (100-325
      mg/d). This antiplatelet treatment could prevent the secondary stroke by
      approximately 22%. Laboratory effective platelet inhibition for the clinician,
      and methods for routine screening evaluation for the laboratory were studied. (1)
      For the standardisation of platelet aggregation technology blood samples of 150
      healthy persons were studied in 5 centres. CARAT TX computerised optical
      aggregometer was used for measuring with collagen (2 microg/ml), epinephrine (10
      microM), arachidonic acid 0.5 mM and ADP 5 microM as inductors. (2) Laboratory
      tests were compared in each centres performed in platelet-rich plasma of ischemic
      cardiovascular and stroke patients (n=823) taking 100-325 mg aspirin/d. (3) Blood
      samples of 555 ischemic stroke patients treated with aspirin (100-325 mg/d), 96
      patients treated with ticlopidine (500 mg/d), and 67 patients treated with
      clopidogrel (75 mg/d) were evaluated, respectively.(1) The mean of maximal
      aggregation (%) - 2SD of untreated controls (n=150) were detected for collagen
      with 64%, epinephrine 59% and ADP 62%. (2) In 823 aspirin treated patients were
      found similar inhibition in different centres with same methods for
      standardisation. The mean inhibition level was in case of collagen 38%,
      epinephrine 37% and ADP 61%. (3) The distribution of ineffective platelet
      inhibition was detected in 17% of aspirin group (collagen and epinephrine), 4% of
      ticlopidine and 18% of clopidogrel group with ADP, respectively. Our findings
      were in the stroke cohort: effective inhibition levels: 36% in aspirin group, 73%
      in ticlopidine and 25% treated with clopidogrel. Platelet aggregation tests could
      help to find the optimal, and "custom taylored" dose of antiaggregating drugs in
      the secondary prevention of ischemic stroke.

PMID- 15258350
TI  - Hemorheological methods in drug research.
AB  - Development of new drugs is a sophisticated process that requires several,
      different methods. In our experiments we have applied two rheological models to
      study experimental and clinically used drugs. The antioxidant properties of
      several agents were estimated by erythrocyte filtration technique. The known
      antioxidant compound vitamin E was used to validate our measurements. An
      experimental cardioprotective agent, H-2545 provided significant protection
      against oxidative changes in red blood cell filterability (p<0.001). Although
      some of the examined, known cardiovascular drugs also showed significant
      antioxidant effect, they were less efficient than H-2545 and the scavenger effect
      of this novel agent exceeded the antioxidant properties of vitamin E.
      Modification of mexiletine with a pyrroline ring improved significantly its
      antioxidant capacity suggesting this molecular segment to be responsible for the
      antioxidant effect. In our second model the antiplatelet effect of experimental
      poly(ADP-ribose) polymerase (PARP) inhibitors was evaluated. Two widely used
      antiplatelet agents: acetyl salicylic acid and eptifibatide served as controls in
      the validation of the measurements. PARP inhibitors reduced ADP-induced platelet
      aggregation in a dose-dependent manner (p<0.05). However, their hindrance on
      platelet aggregation waned as the concentration of ADP rose. Regarding the
      platelets' role in the development of ischemic vascular diseases, the
      antiaggregating property of PARP inhibitors may exert additional beneficial
      effects on tissue blood supply under conditions of compromised vascular flow.

PMID- 15258351
TI  - An expert system for cutaneous blood flow in melanocytic skin lesions.
AB  - A basic tool in microcirculation research is laser Doppler fluxmetry (LDF). The
      chaotic behaviour of the measured LDF-time series acquires mathematical tools
      like, for instance, Wavelets. The notion of contrast is known as useful tool to
      measure differences between two LDF-time series [K. Brauer, Chaos, Attraktoren
      und Fraktale, Logos, Berlin, 2002]. The one time series arises from the blood
      flow in healthy skin and the other from a pigmented symmetric contra lateral skin
      lesion. Our approach is based on taking the contrast from all shorter non
      overlapping time intervals of approximate length 5 or 10 seconds. This gives a
      sample or more precisely, a time series of contrast values. Our goal is an expert
      system to decide between malign and beligne lesions by estimating the probability
      for a maligne lesion. As a data base we again use the same data set as [H.-M.
      Hafner, K. Brauer, M. Eichner, A. Steins, M. Mohrle, A. Blum and M. Junger,
      Wavelet analysis of cutaneous blood flow in melanocytic skin lesions, J. Vasc.
      Res., submitted]. The statistical tool is logistic regression. We can show that
      93% of data are correctly classified. If we check the expert system against the
      independent data base of the Greifswald dermatology department we get 78%
      correctly classified cases. Further work must be done to find a well distributed
      data base for an expert release system.

PMID- 15258352
TI  - Effect of LDL apheresis on oxygen tension in skeletal muscle in patients with
      cardiac allograft vasculopathy and severe lipid disorder.
AB  - In this study, the extent to which intramuscular pO2 is influenced by a single
      HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) was
      investigated in 10 patients with cardiac allograft vasculopathy (CAV) and severe
      lipid disorder. For this purpose, a sterile flexible pO2 microcatheter was
      inserted into the anterior tibial muscle and pO2 monitoring was begun 10 minutes
      before starting apheresis treatment. The intramuscular pO2 values were recorded
      continuously until the end of apheresis treatment and a subsequent 30-minute
      further observation phase. The patients with CAV and severe lipid disorder
      presented with 11.6+/-3.8 mmHg significantly and pathologically reduced
      intramuscular pO2 (p<0.001). LDL apheresis resulted in a significant increase in
      pO2 in the anterior tibial muscle. Thirty minutes after the end of HELP
      apheresis, intramuscular partial oxygen pressure had increased by 162% and showed
      values at this point, 30.3+/-9.8 mmHg, similar to those found in healthy
      subjects.

PMID- 15258353
TI  - Monitoring of myocardial oxygen tension in a beating heart: results of an animal
      model.

PMID- 15258354
TI  - Menopause, hormone replacement therapy and hemorheology.

PMID- 15258355
TI  - Biomaterial-microvasculature interaction on polymers after implantation in mice.
AB  - Biomaterial research is expected to forward new materials to be used as, e.g.,
      implant materials or as scaffolds for tissue engineering. It is central for such
      a scaffold material to create the track on which those cells can inhabitate the
      scaffold needed to rebuild functional tissue substitutes. For the biointegration
      of the implant with the native cellular tissue this must be able to grow on the
      material surface. For the elimination of the degradation products and the
      adeqaute transport of nutrients/gases within the newly formed tissue the
      angiogenesis of new blood vessels is thought to play an important role. In the
      present study, a new biomaterial, a non-porous polymeric AB-network based on
      oligo (epsilon-hydroxycaproat) and oligobutylacrylat, was implanted in animals.
      Male NMRI mice were implanted subcutaneously for one week to nine weeks.
      Immediately after the explantation, the probes were examined histologically.
      Already one week after implantation, there was a strong tissue-integration of the
      polymer. Importantly, blood vessels appeared at the polymer surface. At nine
      weeks after implantation the tissue integration was stronger than after one week
      and blood vessels were still observed in the periimplant tissue. The mechanism of
      the early integration of the polymer is not clear. The relationship between the
      new periimplant vessels and the integration of the polymer has to be studied.

PMID- 15258356
TI  - Endothelium and hemorheology.
AB  - Hemorheological alterations which can be found in ischaemic vascular diseases are
      well known and widely studied; less clear is the relationship between these
      alterations and endothelial function. Our studies showed that modifications in
      endothelial function caused by physical stress are associated with a worsening in
      hemorheological parameters mainly in patients affected by ischaemic vascular
      diseases: major vascular alterations have been found in patients with very high
      levels of plasma markers endothelial dysfunction. The control of the basal tone
      of the vessels is given by the complex interaction between vasoconstrictor and
      vasodilator endothelial factors and when this equilibrium is broken we have the
      endothelial dysfunction. From a methodological point of view we can find an
      endothelial dysfunction index determining the various substances produced by the
      endothelium, but it is very difficult to have a value which clearly identifies
      the real state of the endothelial alteration. The function of the NO, which is
      one of the more powerful endogenous vasodilators and whose synthesis is catalysed
      by nitric oxide synthase (NOS), can be determined by the ratio between blood
      concentrations of citrulline and arginine (the co-product and the precursor of
      the way of NO synthesis), which represents the level of activity of the enzyme. A
      very affordable index of the endothelial dysfunction is the asymmetric
      dimethylarginine (ADMA), a powerful endogenous inhibitor of NOS; in fact several
      studies demonstrated a strong relationship between ischaemic vascular diseases
      and high levels of plasma ADMA. Evaluation of these parameters is measured by
      means of high performance liquid chromatography (HPLC): this technique provides
      very affordable results and allows to obtain evaluations of substances in very
      small concentrations, like ADMA.

PMID- 15258357
TI  - Blood rheology in patients with diabetes mellitus.
AB  - Blood rheology is now receiving increasing attention as an important potential
      contributory factor to diabetic angiopathy. This study was designed to provide
      evidence for and against early hemorheological abnormalities in diabetes mellitus
      (DM). For this purpose, blood viscosity, RBC aggregation, hematocrit, and plasma
      protein's levels of both fibrinogen and albumin were measured in 86 uncomplicated
      patients with DM (45 type 1 and 41 type 2). Patients with HbA1c < 7.5% were
      considered as having good glycemic control (GGC), while those with HbA1c > 8.5%
      as having poor glycemic control (PGC). Patients with type 1 DM showed normal
      blood viscosity at both shear rates high and low, while native hematocrit,
      fibrinogen, and RBC aggregation were significantly elevated and albumin
      significantly reduced when compared with healthy volunteers. Patients with type 2
      DM showed more marked impairments associated with an increased low shear rate
      blood viscosity, when compared with patients with type 1 DM. Comparison between
      two subgroups of patients, both of which with type 1 DM and of similar disease
      duration of <5 yrs, with GGC or PGC showed that impaired blood rheology does
      depend on the quality of glycemic control. Differences were attenuated after a
      disease duration of >15 yrs. These findings suggest that early hemorheological
      impairments in patients with type 1 DM are dependent upon the glycemic control.
      In contrast, hemorheological impairments appear to be inevitable after a mean
      disease duration of 15 yrs even if there is a GGC. Aggravation of hemorheological
      abnormalities in patients with type 2 DM might depend upon the hemorheological
      effects of other metabolic abnormalities related to insulin resistance rather
      than the quality of glycemic control.

PMID- 15258358
TI  - Effects of dietary triglycerides on rheological properties of human red blood
      cells (abstract).
AB  - Atherogenic diets rich in saturated fat and cholesterol influence the blood
      viscosity and red blood cell (RBC) aggregability, the parameters associated with
      increased risk of circulatory disorders. However, little is known about the
      effect of triglycerides, which are the major dietary lipid form in humans, on
      blood rheology. Therefore, we studied the effects of postprandial plasma
      triglyceride levels on human RBC indices, hematological parameters, RBCs
      aggregation velocity and whole blood viscosity. For this purpose, whole blood was
      collected 2 hours after high-fat or low-fat meal. Proteins, triglycerides and
      cholesterol levels of plasma were analysed, and RBCs rouleaux formation rate was
      measured in 70% autologous plasma using a low-shear rheoscope. There were no
      significant differences in hematological parameters, RBC indices, whole blood
      viscosity, plasma protein and cholesterol content between high-fat and low-fat
      blood samples. However, a significant increase in rouleaux formation rate was
      observed in samples with high postprandial triglyceride levels, when compared
      with low-triglyceride samples. Plasma triglyceride levels correlated
      significantly with rouleaux formation rate. In conclusion, these results suggest
      that diet-dependent alterations of plasma triglyceride levels as well as possible
      changes in the cell membrane lipid composition lead to RBC hyperaggregability.

PMID- 15258359
TI  - Blood rheology as a marker of venous hypertension in patients with venous
      disease.
AB  - During chronic venous insufficiency (CVI), several microvascular functional
      abnormalities, due to venous hypertension, develop. To look for blood rheological
      consequences of venous hypertension "VH", whole blood viscosity and its main
      determinants were measured in 11 normal controls and 36 patients with CVI exposed
      to a short-term experimental VH. Patients were subdivided into 2 groups according
      to the severity of their disease. Blood was taken from a foot vein before and
      after VH, which was induced by appling a pneumatic tourniquet to 100 mmHg for 15
      minutes. Whole blood viscosity at low and high shear rates, red blood cell (RBC)
      aggregation, RBC rigidity, plasma viscosity and proteins as well as red and white
      blood cell (WBC) counts were recorded. Patients at baseline, i.e., before
      application of the tourniquet, showed several hemorheological abnormalities such
      as an increased RBC aggregation, increased low shear rate viscosity, and a
      significant elevation in plasma fibrinogen level. Patients with more severe CVI
      had more marked hemorheological changes. The short term VH in patients led to
      further aggravation of these changes. There were also at baseline lower values,
      however not significantly, of hematocrit and RBC count, suggesting that
      hemoconcentration is not a feature of CVI. These same parameters were slightly,
      however not significantly, increased after VH, indicating a fluid escape into the
      extravascular space. A significant fall in WBC count was also observed after VH,
      in keeping with the white cell trapping hypothesis. In conclusion, even a short
      term VH is able to induce several hemorheological impairments, which are probably
      involved in the failure of the microcirculation and hence the initiation of
      tissue damage in patients with CVI.

PMID- 15258360
TI  - Possible involvement of oxidative stress in exercise-mediated platelet
      activation.
AB  - In this study, we have attempted to verify whether a single bout of strenuous
      exercise performed by sedentary healthy individuals may interfere with the
      mechanisms controlling platelet sensitivity through exercise-related
      modifications of plasma oxidant/antioxidant equilibrium. Strenuous exercise
      resulted in an increased ADP- and collagen-evoked platelet aggregation associated
      with modified membrane fluidity and ion homeostasis. We also observed an enhanced
      plasma accumulation of secondary products of lipid peroxidation together with an
      increased susceptibility of low density lipoprotein (LDL) to in vitro oxidation
      and a decreased total plasma antioxidant potential. Notably, an acute elevation
      of nitrite/nitrate (NOx) amount was detected in plasma, whilst a decreased NOx
      content was measured in platelets. Findings of the current study suggest that
      oxidative stress induced by acute strenuous exertion may interfere with platelet
      responsiveness by promoting ox-LDL-mediated platelet activation and by decreasing
      platelet-derived nitric oxide bioactivity.

PMID- 15258361
TI  - In vitro effects of melatonin on the filtrability of erythrocytes in SNP-induced
      oxidative stress.
AB  - Erythrocyte deformability is one of the most important charactheristics of
      erythrocytes for an effective microcirculatory function and is affected from a
      number of factors, including the oxidative-damage-induced by nitric oxide (NO).
      This study was performed to investigate the effects of in vitro melatonin
      incubation on the antioxidant status and deformability of erythrocytes in sodium
      nitroprusside (SNP), a nitric oxide donor, induced oxidative stress. 40 blood
      samples taken from the adult healthy people were divided into 4 groups randomly
      and incubated with saline, SNP (1 mM), melatonin (MEL, 1 mM), MEL + SNP and SNP +
      L-NAME (5 mM) respectively. Relative filtration rate (RFR), relative filtration
      time (RFT) and relative resistance (Rrel) were determined as the indexes of
      erythrocyte filterability. In addition, malondialdehyde (MDA, as an index of
      lipid peroxidation) and the antioxidant activities of glutathione peroxidase (GSH
      Px), superoxide dismutase (SOD) and catalase (CAT) were also determined in the
      red blood cells of all groups revealing the oxidant-antioxidant activity. RFT and
      the Rrel of the erythrocytes incubated with SNP increased significantly (p<0.05)
      whereas the RFR of the erythrocytes decreased (p<0.05) in comparison to all
      groups. This reduction in RFR was prevented with both L-NAME or MEL incubation.
      Furthermore, MEL was found to be significantly efficient in preventing the
      erythrocytes from lipid peroxidation in these groups. In addition, GSH-Px and SOD
      activities were elevated with SNP incubation reflecting the oxidative stress in
      erythrocytes, whereas the CAT activity remained unchanged. Melatonin has no
      significant effect on the GSH-Px and CAT activity but, it caused a significant
      decrease in SOD activity (p<0.05). These results reveal that, melatonin can
      protect the erythrocytes from impaired deformability in SNP-induced oxidative
      stress due to antioxidant effects as revealed by lipid peroxidation and
      antioxidant enzyme activities.

PMID- 15258362
TI  - The in vivo antioxidant effectiveness of alpha-tocopherol in oxidative stress
      induced by sodium nitroprusside in rat red blood cells.
AB  - Reactive oxygen species avidly reacts with nitric oxide (NO) producing cytotoxic
      reactive nitrogen species capable of nitrating proteins and damaging other
      molecules which leads to the reduction of erythrocyte deformability. The aim of
      this investigation was to assess the importance of alpha-tocopherol (Vit-E) in
      the total antioxidant status of the erythrocytes in sodium nitroprusside (SNP), a
      nitric oxide donor, induced oxidative stress and its relation to erythrocyte
      deformability. Male Swiss Albino rats were used in 4 groups, comprising of 10
      animals in each group. The first group was the control, and the other groups were
      administered SNP (10 mg/kg, i.p.), Vit-E (10 mg/kg, i.p.) + SNP, and SNP + L-NAME
      (10 mg/kg, i.p.), respectively. Relative filtration rate (RFR), relative
      filtration time (RFT) and relative resistance (Rrel) were determined as the
      indexes of erythrocyte deformability. In addition, malondialdehyde (MDA, as an
      index of lipid peroxidation) and nitric oxide levels and the antioxidant
      activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and
      catalase (CAT) were also determined in the red blood cells of all groups
      revealing the oxidant-antioxidant activity. RFT and the Rrel of the erythrocytes
      of the SNP-treated rats increased significantly (p<0.05) whereas the RFR of the
      erythrocytes decreased (p<0.05) in comparison to all groups reflecting the
      impaired deformability. This reduction in RFR was prevented with both L-NAME or
      Vit-E incubation. Vit-E has also reduced the Rrel of the erythrocyte which
      reveals that it has improved the erythrocyte deformability. Lipid peroxidation
      was suppressed by Vit-E and L-NAME significantly, where the red blood cell
      deformability was improved. Furthermore, SOD and CAT activities were
      significantly stimulated with SNP treatment (p<0.05), where as GSH-Px remained
      unchanged. In the contrary, GSH-Px activity was triggered significantly by Vit-E
      administration, whereas the SOD and CAT activities were reduced (p<0.05). As a
      result, these data reveal that Vit-E improves the erythrocyte deformability in
      SNP-induced oxidative stress by its antioxidant effects on the lipid peroxidation
      and antioxidant enzyme activities.

PMID- 15258363
TI  - Reciprocal relationships between blood lactate and hemorheology in athletes:
      another hemorheologic paradox?
AB  - Blood lactate increases during exercise. Although this increase was classically
      interpreted as a "Pasteur-like effect" resulting from anaerobiosis, it is now
      clear that it mostly results from a shift in the balance of oxidation of
      substrates in the muscle, with carbohydrate becoming the predominant fuel.
      However, we have repeatedly observed that the rise in blood lactate during
      exercise is correlated to blood viscosity and red cell aggregation. More recently
      we investigated this issue with the modelling of postexercise lactate kinetics,
      that allows a fair evaluation of lactate production by muscles (gamma1) and
      lactate disappearance (gamma2). Postexercise red cell aggregation (Myrenne M1)
      appears to be correlated to gamma2. Thus microcirculatory adaptations influenced
      by red cell aggregation may influence lactate disposal, adding its effect to that
      of the balance between carbohydrates and fat. On the other hand, the rise in
      blood lactate seems to induce some alterations in erythrocyte rheology at
      exercise. Correlations between its concentrations during exercise and erythrocyte
      rigidity support the concept that lactate, at least when it rises above the 4
      mmol.l(-1) threshold impairs red cell deformability. Moreover, it seems that
      endurance training influences erythrocyte response to lactate. While lactate did
      not in vitro affect erythrocyte aggregation, it impaired (as expected)
      erythrocyte deformability in sedentary subjects but it (unexpectedly) improved it
      in trained subjects. This difference may be due to training-induced adaptations
      in erythrocyte metabolism, including transmembrane transfer via monocarboxylate
      transporters which show marked alterations in this context. This specific
      training-induced pattern of response to lactate may provide an alternative
      explanation to the exercise-induced arterial hypoxemia that occurs in such
      athletes.

PMID- 15258364
TI  - Blood fluidity is related to the ability to oxidize lipids at exercise.
AB  - We previously reported in rugbywomen correlations between RBC deformability and
      the ability to oxidize at exercise more lipids. This surprising finding might of
      course be spurious, or reflect the importance of the balance of substrates at
      exercise on baseline parameters that regulate blood rheology. Actually, the
      capacity of skeletal muscle to utilize either lipid or carbohydrate as fuels
      strongly influences whole body metabolism both at rest and during exercise. While
      the healthy skeletal muscle has substantial metabolic flexibility and is able to
      switch from predominantly lipid o oxidation during fasting or endurance exercise
      to increased glucose oxidation in conditions of insulin stimulation, obese
      individuals and those with type 2 diabetes manifest higher lipid oxidation during
      insulin-stimulated conditions despite lower rates of lipid oxidation during
      fasting or prolonged exercise. A low ability to oxidize and to periodically
      deplete triglyceride in muscle is associated with raised blood lipids. In
      addition, high carbohydrate oxidation rates in the mitochondrion are likely to
      promote more free radical generation. An increase in either blood lipids or free
      radicals is likely to induce profound hemorheological effects. We present here
      hemorheological studies in various populations with the use of exercise
      calorimetry in order to assess this switch of substrates. These studies further
      evidence negative correlations between the ability to oxidize lipids at exercise
      and parameters of blood viscosity. Correlations found between RBC deformability
      and the ability to oxidize at exercise more lipids may be due to effects of
      endurance training on lipid oxidation which may in turn modify both lipid
      metabolism and free radical generation, thus influencing RBC rheology.

PMID- 15258365
TI  - Ultrasound scattering from concentrated suspensions of aggregated red cells in
      shear flow.
AB  - Ultrasound scattering technique is used to investigate dynamics of reversible
      fractal aggregates in dense suspensions and analyze shear break-up processes of
      Rayleigh fractal clusters. On the basis of an homogenous fractal flocculation and
      the hybrid scattering model in the Rayleigh scattering regime, a first order
      expression of the ultrasound scattering cross-sectional area per unit of volume
      (backscattering coefficient) is derived for a dense distribution of correlated
      Rayleigh fractal clusters. From the scaling laws for shear break-up of reversible
      aggregates in concentrated suspensions, a rheo-acoustical study is then proposed
      to describe the shear stress dependence of the low frequency scattered power per
      unit of volume. In a second part, experimental flow dependent changes of the
      ultrasound backscattering coefficient in a plane-plane flow geometry were
      reported to analyze shear break-up processes of hardened or deformable red cell
      aggregates in polymer solution (neutral dextran polymer). Rheo-acoustical
      experiments were examined within the framework of the effective mean field
      approximation and the proposed rheo-acoustical model. The ability of ultrasound
      scattering to determine the critical disaggregation shear stress inducing a
      complete disaggregation and to give quantitative information on particle surface
      adhesive energy are finally analyzed.

PMID- 15258367
TI  - Experimental determination of blood permittivity and conductivity in simple shear
      flow.
AB  - The paper is concerned with the determination of blood permittivity and
      conductivity in Poiseuille and Couette simple shear flows. The experimental
      procedure, based on dielectric spectroscopy, evidences the sensitivity of blood
      electric properties to the applied frequency and local shear rate magnitude. The
      method evidences the possibility to correlate (for well-defined flow geometry)
      magnitude of shear rate, and consequently the shear stress level, with spectra
      permittivity of blood.

PMID- 15258366
TI  - Blood flow resistance with vibration and its effect on blood cell migration.
AB  - The present study investigated the effect of transverse vibration on the hemo
      rheological characteristics of blood flow using a newly designed pressure
      scanning capillary viscometer. As a transverse vibration was applied, aggregated
      blood cells become disaggregated. Frequency of vibration was found to be the main
      parameter causing hemo-rheological changes. For RBC suspension in a non
      aggregating medium (Dextran 40), increasing frequency of vibration caused
      decreased flow resistance. Meanwhile, flow resistance for whole blood increased
      with frequency of vibration. These seemingly contradictory results could be
      interpreted without conflict when a comprehensive mechanism of cell migration
      under vibration is elucidated. The present study confirmed that vibration
      diminishes RBC aggregation, which triggers two different cell migration
      mechanisms and subsequently resulted in either increasing or decreasing the flow
      resistance.

PMID- 15258368
TI  - Type 2 diabetics with higher plasma viscosity exhibit a higher blood pressure.
AB  - Among hemorheologic parameters, plasma viscosity is one of the most studied in
      epidemiology, so that it has emerged as an independent risk factor. In diabetes,
      plasma viscosity is frequently elevated. For this reason we tried to define
      characteristics of non-insulin dependent diabetics with high plasma viscosity
      (>1.45 mPa.s) and whether they were more insulin resistant and/or exhibited other
      hemorheologic disturbances. 12 subjects (age 56.1+/-11.7; BMI 28.6+/-4.8) were
      thus found to have a value of plasma viscosity >1.45 mPa.s. They were compared to
      20 age and BMI-matched NIDDMs. Patients have similar insulin sensitivity, HbA1c,
      and fibrinogen. RBC aggregation, rigidity and hematocrit were not significantly
      different. Whole blood viscosity at high shear rate was slightly higher (p=0.05).
      When corrected for hematocrit whole blood viscosity is no longer different.
      However, hematocrit was not lower in subjects with hpl >1.45. By contrast blood
      pressure was markedly higher (systolic: 177.5+/-2.5 mmHg vs 140+/-8 mmHg, p<10(
      8); diastolic 110+/-14 vs 83+/-9 mmHg, p<10(-9); mean 132+/-18 mmHg vs 102+/-7
      mmHg p<10(-9)). Therefore, in NIDDM, higher plasma viscosity, regardless insulin
      resistance and adiposity, is strongly related to blood pressure.

PMID- 15258369
TI  - Evaluation of the hemorheological and neurosonographic relationship in patients
      with cerebrovascular diseases.
AB  - During the last fifteen years some of our priority scientific topics of research
      were hemorheological and neurosonographic investigations in 229 patients with
      different forms of cerebrovascular diseases (CVD): 75 patients with asymptomatic
      CVD (ACVD), 65 patients with transient ischemic attacks (TIAs) and 89 patients
      with chronic unilateral cerebral infarctions (UCI). The findings were compared
      with 70 healthy persons. The main estimated hemorheological parameters were
      hematocrit (Hct), apparent whole blood viscosity (WBV), plasma viscosity (PV) and
      fibrinogen (Fib). They were correlated with the following sonographic parameters,
      obtained by extracranial and transcranial Doppler sonography: blood flow
      velocities (BFV) and peripheral resistance index of Pourcelot (RP) of the major
      arteries of the head and the basal cerebral arteries and vasomotor reactivity
      indices (VMRI) of the middle cerebral arteries (MCA). Among the hemorheological
      variables the correlations of Hct with the velocity sonographic parameters
      predominated in all groups. Significant positive correlations between Hct, WBV
      and the RP of the internal carotid artery and MCA were found in patients with
      CVD. In UCI the increase in Hct and Fib was associated with a decrease in BFV of
      the collateral circulation where aging and high mean blood pressure were
      additional risk factors for impairment of the cerebral hemodynamics. Plasma
      viscosity was found to correlate with cerebral VMRI of MCA in patients with UCI.
      The clinical impact of these findings and their relation to the therapeutic
      strategy in CVD are discussed.

PMID- 15258370
TI  - Hemorheological and hemodynamic effects of high molecular weight polyethylene
      oxide solutions.
AB  - Hemorheological and hemodynamic effects of high molecular weight polyethylene
      oxide (PEO) solutions have been studied in vitro and in vivo at 30 experimental
      dogs. The rheological behaviour of the PEO solutions and of blood samples has
      been assessed by rotational viscometers at 20 degrees C, 25 degrees C and 37
      degrees C. An addition of PEO solutions to the blood in vitro has modified its
      rheological behavior, depending on the shear rates, concentration and
      temperature. Saline with aqueous PEO solutions at the concentration of 500 ppm
      has been infused into the blood circulation of the experimental dogs to achieve
      the total concentration in blood of 20-30 ppm. The following parameters cardiac
      output, mean arterial blood pressure, central venous pressure, pulse frequency,
      blood volume flow in the femoral artery, total vascular resistance and blood
      viscosity before and after the infusion of PEO solutions have been studied. The
      main observed effect was a decrease of the hemodynamic resistance in the
      cardiovascular system up to 40% below the baseline after infusion of PEO
      solutions.

PMID- 15258371
TI  - Extension of equations for predicting viscosity parameters with whole body
      bioelectrical impedance to a sedentary population.
AB  - In a previous paper we determined predictive equations for predicting viscosity
      parameters with whole body Bioelectrical impedance (BIA) in athletes. We have
      tried to extend this analysis to a sedentary population. 36 sedentary obese or
      insulin resistant patients (40.36+/-2.30 years; 85.77+/-3.54 kg; 165.93+/-1.56
      cm) were enrolled into this study. Body composition was assessed with a
      multifrequency bioelectrical impedancemeter Dietosystem Human IM Scan that uses
      low intensity at the following frequencies: 1, 5, 10, 50 and 100 kHz. Analysis
      was performed with the software Master 1.0 that gives the choice among 25
      published equations for body composition calculation. Viscometric measurements
      were done at 1000 s(-1) with a falling ball viscosimeter (MT 90 Medicatest).
      Hematocrit was measured with microcentrifuge. Two hemorheological parameters were
      independently correlated with impedance (Z) measurements at 50 kHz: whole blood
      viscosity (WBV) (r=0.541, p=0.01) and hematocrit (Hct) (r=-0.686, p=0.01). New
      equations slightly different from those we report in the previous paper were
      found. These findings confirm our previous reports of relationships between whole
      body electric properties and factors of blood viscosity in athletes and allow the
      use of BIA to a sedentary population. Obviously, extension of this study will be
      needed to determine if BIA can be used to generalize predictive equations in both
      sedentary and trained individuals.

PMID- 15258372
TI  - Hemorheological disorders and arteriolar resistance during ischemic heart
      disease.
AB  - It could be conjectured that the hemorheological disorders are involved in
      development of the ischemic heart disease. But this fact was so far
      insufficiently cleared up. The present studies were carried out in patients with
      various forms of chronic ischemic heart disease. We investigated the most
      significant factor of rheological disorders in the microcirculation, the
      erythrocyte aggregability, with a technique that provided us with the direct and
      quantitative data. Simultaneously we investigated in the same patients the tone
      of the resistance arteries of the hand with an original non-invasive technique.
      We found that the erythrocyte aggregability increased almost twice in the blood
      of investigated patients as compared to the healthy control group. The
      aggregability was positively correlated with severity of the disease. The most
      pronounced hemorheological disorders were found in the patients with the heart
      failure. As to the arteriolar resistance index, it was increased only in 45
      percent of all the investigated patients and no significant difference between
      the patients with the heart failure and without it was found available. We
      concluded that the blood rheological disorders represent themselves a factor that
      plays a significant role in pathogenesis of development of the heart disease.

PMID- 15258373
TI  - Effect of nitric oxide initial blood levels on erythrocyte aggregability during
      12 hours from ischemic stroke onset.
AB  - The aim of study was the investigation of blood nitric oxide (NO) and nitrates
      (NO2) levels in 12 hours of ischemic stroke onset and establishment of
      correlation of these data with erythrocyte aggregability and initial ischemic
      lesion size. 48 patients, aged 45 to 70 years, 26 female, 22 male were
      investigated. Glasgow Coma Scale (GCS) and National Institute Health Stroke Scale
      (NIHSS) assessed initial neurological impairment. Patients were divided in mild
      and severe stroke groups. Control comprised 20 healthy individuals. Ischemic
      lesions were evaluated on conventional MRI scans. NO levels were measured by
      electron paramagnet resonance (EPR) method. NO2 levels were defined by
      spectrophotometer method. Erythrocyte aggregability index (EAI) was measured by
      sound method [Biorheology 30(2) (1993), 153-161]. Pearson correlation and
      multivariate model of logistic regression was applied. Significant negative
      correlation was established between NO initial blood levels and the EAI (r=-0.75;
      p<0.001), as well as between blood NO2 and NO initial levels and ischemic lesion
      size (r=-0.79, p<0.01; r=-0.61, p<0.02, respectively). Endothelialy derived NO
      correlates with erythrocyte aggregability and probably has a positive impact on
      restoration of cerebral blood flow in the initial stage of acute brain ischemia.

PMID- 15258374
TI  - Blood rheological abnormalities in the microcirculation during experimental
      traumatic shock.
AB  - OBJECTIVE: To find whether the principal indices of blood rheological disorders
      related to the microcirculation undergo drastic changes during the traumatic
      shock. METHODS: RBC aggregability and deformability, as well as the systemic
      hematocrit, were assessed in white laboratory rats with the techniques that
      provided us with direct and quantitative data. RESULTS: We found that in the
      experimental animals the RBC aggregability was sharply increased, the RBC
      deformability significantly decreased, while the systemic hematocrit underwent
      considerable lowering during the traumatic shock. CONCLUSION: The blood
      rheological properties are significantly disordered during development of the
      traumatic shock.

PMID- 15258375
TI  - Do hemorheological alterations play any role in the development of thrombotic
      events in Behcet's disease?
AB  - Behcet's disease (BD) is associated with an increased thrombotic risk, although
      the prothrombotic mechanisms are not clearly defined. Alterations in blood
      rheology, specially increased erythrocyte aggregation has been suggested to play
      an important role in the development of thrombotic events in patients with
      Behcet's disease. In order to ascertain whether any rheological parameter could
      be involved in the pathogenesis of thrombotic events in Behcet's disease we have
      determined plasmatic lipids, fibrinogen, hematocrit, erythrocyte aggregation
      (Myrenne aggregometer), erythrocyte deformability (Rheodyn SSD), blood viscosity
      (Brookfield viscosimeter), plasma viscosity (Fresenius capillary viscosimeter)
      and erythrocyte indexes in Behcet's patients with a non-active disease when
      sampling, and a well matched control group. The patient group was made up of 40
      Behcet's patients (20 male, 20 female aged 43+/-12 years) and the control group
      comprised 70 healthy volunteers (24 male, 46 female aged 45+/-13 years). Twelve
      of the 40 Behcet's patients have had a previous documented history of deep vein
      thrombosis at least six months before entering the study, and the other 28 did
      not. When patients and controls were compared, patients showed a statistically
      higher fibrinogen level (p=0.002), plasma viscosity (p=0.003), blood viscosity
      (p=0.021) and erythrocyte aggregation (p=0.049), the other rheological parameters
      not being statistically significant. No differences were observed in the
      rheological parameters when patients with and without a previous thrombotic
      episode were compared. Our results suggest that rheological alterations do not
      seem to play any role in the development of thrombotic events in patients with
      Behcet's disease.

PMID- 15258376
TI  - Rheological profile in severe and morbid obesity. Preliminary results.
AB  - The association of hemorheological alterations with morbid obesity remains a
      question of debate. In order to ascertain whether morbid obese subjects show
      certain hemorheological alterations which might be involved in the higher
      thrombotic risk which characterizes these subjects, we determine glucose, plasma
      lipids, apolipoproteins, fibrinogen, hematocrit, blood viscosity (Brookfield
      DVIII viscosimeter), both at native and corrected hematocrit of 45%, plasma
      viscosity (Fresenius capillary viscosimeter), erythrocyte aggregation (Myrenne
      aggregometer), both at stasis and at 3 s(-1) at 45% hematocrit and erythrocyte
      indexes in 41 morbid obese subjects (32 female, 9 male aged 33+/-10 years), and
      in a well matched non-obese control group (40 female, 15 male, aged 32+/-10
      years). Mean BMI in the morbid obese group was 44.9+/-6.7 kg/m2 vs 23.5+/-4.8
      kg/m2 in the control group (p<0.001). Morbid obese subjects when compared with
      the control group showed a statistically higher glucose level (p<0.001), LDL
      cholesterol (p=0.019), triglycerides (p<0.001), apoB (p=0.019), apoB/A1
      (p<0.001), fibrinogen (p<0.001), erythrocyte aggregation (p<0.001), and a
      statistically lower HDL-cholesterol (p<0.001). No differences between both groups
      were observed regarding total-cholesterol, plasma viscosity, blood viscosity and
      hematocrit (p=0.109; p=0.690; p=0.510; p=0.950), respectively. After the
      adjustment for BMI, differences in glucose, LDL-cholesterol, triglycerides, apoB,
      apoB/A1, and erythrocyte aggregation did not reach the statistical significance,
      and differences in fibrinogen were borderline significant (p=0.051), showing a
      direct effect of BMI on the detected differences between obese and non-obese. Our
      results suggest that in morbid obese subjects the increased fibrinogen levels and
      the altered lipid profile associated with their higher BMI, could in addition to
      its known mechanisms on haemostasis, favour both venous and arterial thrombotic
      events by enhancing erythrocyte aggregation.

PMID- 15258377
TI  - Effect of a hypocaloric diet on lipids and rheological profile in subjects with
      severe and morbid obesity. A follow-up study.
AB  - Discrepant results have been published regarding modifications of rheological
      parameters in obese subjects after a low caloric diet (LCD). In order to
      ascertain whether a decrease in BMI associated to a LCD, is accompanied by
      changes in the hemorheological parameters, we determined in 41 morbid obese
      subjects (32 female, 9 male aged 33+/-10 years) BMI, glucose, plasmatic lipids
      and apolipoproteins, fibrinogen, blood viscosity (Brookfield viscosimeter),
      plasma viscosity (Fresenius capillary viscosimeter), erythrocyte aggregation
      (Myrenne aggregometer), hematocrit and erythrocyte indexes, before starting on a
      LCD and 1 and 3 months after. During the first month obese subjects received a
      very low caloric diet (VLCD) (Modifast) providing 458 kcal per day. The second
      and third month they received a LCD providing 1500 kcal/day for men and 1200
      kcal/day for women. One month after starting on a VLCD, a statistical significant
      decrease in glucose (p<0.001), Total-cholesterol (p<0.001), LDL-cholesterol
      (p<0.001), triglycerides (p=0.012), apoB (p<0.001) and erythrocyte aggregation
      (p<0.001) were observed together with a concomitant decrease in BMI (p<0.001).
      The expected decrease in HDL-cholesterol associated with a low fat diet was also
      noted in these individuals. No changes in fibrinogen, hematocrit, blood viscosity
      or plasma viscosity were observed. At 3 months only a slight increase in BMI was
      observed regarding the one month period, glucose being the only parameter which
      remained statistically lower. All the other significant parameters returned to
      their basal values at 3 months. VLCD (Modifast) is associated to a significant
      decrease in BMI with the corresponding improvement in glucose, lipids and
      erythrocyte aggregation at one month. However a LCD alone does not produce a
      further decrease in weight and both lipids and erythrocyte aggregation return to
      the basal situation at three months.

PMID- 15258378
TI  - Influence of plasmatic lipids on the hemorheological profile in healthy adults.
AB  - Some hemorheological parameters constitute risk factors for ischemic
      cardiovascular events. Most of these hemorheological factors are determined by
      the erythrocyte intrinsic properties and the high molecular weight plasmatic
      proteins, especially fibrinogen. The contribution of the plasmatic lipids to
      hemorheological factors is not well established. With this aim we determined
      hemorheological parameters in 112 healthy volunteers (62 males, 50 females) aged
      35+/-10 years, range 19-54 years, members of our hospital staff. A complete set
      of rheological test was performed. Blood viscosity (BV) 230 sec(-1), plasma
      viscosity (PV), erythrocyte aggregation index (EAI), erythrocyte elongation index
      (EEI), hematocrit and fibrinogen. We also determined plasmatic lipids including
      total cholesterol (T-Ch) and its fractions (HDL-Ch, LDL-Ch, VLDL-Ch),
      triglycerides, lipoproteins (Apo B, Apo A(1), B/A(1)). Exclusion criteria were
      concomitant cardiovascular risk factors or any other associated pathology. Our
      results show a positive correlation between BV 230 sec(-1) and triglycerides
      (r=0.335) and negative with HDL-Ch (r=-0.451) (p=0.01), respectively; PV shows a
      positive correlation with T-Ch (r=0.297), LDL-Ch (r=0.298) and Apo B/A (r=0.290)
      (p=0.01). The EEI was negatively correlated with TG (p=0.05). Of all the
      rheological parameters evaluated, EAI is the factor which shows the highest
      significant correlation with plasmatic lipids: T-Ch (r=0.515), TG (r=0.303), LDL
      Ch (r=0.507) and Apo B/A ratio (r=0.403); (p=0.01). These results suggest that
      plasmatic lipids contribute to modulate the blood rheological properties, slowing
      blood flow, favouring the development of atherothrombotics events, especially in
      stenotic areas or bifurcations in the vascular tree.

PMID- 15258379
TI  - Local hemorheological disorders during chronic inflammation.
AB  - Hemorheological parameters were investigated before, during, and after the
      standard burn of the distal part of the rabbits' ear shell (54 degrees C for 3
      minutes). The erythrocyte aggregation was investigated with the "Georgian
      technique" and the local hematocrit was determined by centrifugation of blood
      samples from the inflammatory focus. In addition, we determined the size of the
      inflammatory edema in the ear shell. We found that the erythrocyte aggregability
      rised by 3.7 times in the venous blood flowing out from the inflammation focus
      while the hematocrit increased 1.6 times as compared to the microcirculation in
      the contralateral (control) ear shall. The thickness of this latter related to
      edema development increased three times. All the mentioned changes disappeared
      within five days after start of the experiments. We concluded that in the aseptic
      inflammatory foci the erythrocyte aggregability increases considerably in the
      microcirculation producing capillary stases and enhancing the local hematocrit.
      The hemorheological disorders were not spread to other parts of the circulatory
      bed.

PMID- 15258380
TI  - Direct beneficial effect of insulin on blood rheological disorders in the
      microcirculation.
AB  - Under both the in vivo and in vitro conditions we investigated the insulin effect
      on the most significant factor disturbing the blood rheological disorders in the
      microcirculation, the red blood cell aggregability. The in vivo studies we
      carried out in the 42 insulin treated diabetic patients (diabetes mellitus type
      II), as well as conducted the in vitro investigations of the blood both of the
      diabetic patients (24) and of the healthy people (20) where the insulin was added
      to the blood ex vivo. The RBC aggregability in blood investigated with the
      "Georgian technique" was found significantly enhanced, by about 100 per cents in
      the diabetic patients. Under the in vivo conditions insulin administered
      intravenously decreased the RBC aggregability almost to the normal level in
      diabetic patients. In addition, in the in vitro studies we found that the insulin
      lowered significantly the RBC aggregability when it was significantly enhanced by
      addition of Dextran-500, as well as in the blood of patients with the ischemic
      brain infarcts. The decreasing effect on the RBC aggregability was observed even
      in the healthy control group where the RBC aggregability was in a normal range.

PMID- 15258381
TI  - Are there two functionally distinguished Neu5Gc pools with respect to rouleau
      formation on the bovine red blood cell?
AB  - Bovine red blood cells (RBCs) do not exhibit any aggregation tendency in
      autologous plasma and, therefore, all bovine rouleaux obtained in vitro are
      regarded as artificial. The present study reports the bovine RBC rouleau
      formation by either bovine or human fibrinogen and Ca2+ ions. The phenomenon was
      induced through two-step cell incubation: in 0.9% NaCl and 1% bovine albumin at
      37 degrees C for 30 min followed by 20 hrs incubation at 30 degrees C in the
      fresh solution supplemented with 10 mM glucose. Its mechanism is unknown. During
      the incubation the number of N-glycolylneuraminic acid molecules per cell
      decreased from 48.1 to 44.9 amoles, which accounted for 7%. The treatment of RBCs
      with V. cholerae sialidase under the same conditions resulted in a 94% drop in
      the Neu5Gc quantity and did not induce the rouleau formation in the same
      fibrinogen preparation. The preliminary results rise a question whether the bulk
      of sialic acid is required in the aggregation of bovine erythrocytes under static
      conditions. Only a minor pool of Neu5Gc seems to be responsible for suppression
      of the phenomenon.

PMID- 15258382
TI  - On the interrelationships between erythrocyte aggregation, plasma viscosity and
      the total peripheral resistance in arterial hypertension.
AB  - A probable conjunction of hemodynamic- and rheological variables was tested in
      hypertensive patients. Most pronounced correlation was fixed for some indices
      (sizable in value for plasma viscosity and small but distinct for blood pressure
      and ZSR) vs. total peripheral resistance. These results of a small scale
      elaboration are encouraging to get up a study extension.

PMID- 15258383
TI  - Plasma lipid levels, blood rheology, platelet aggregation, microcirculation state
      and oxygen transfer to tissues in young and middle-aged healthy people.
AB  - It has been reported that dyslipidemia is associated with rheological and
      microcirculatory abnormalities in patients with ischaemic heart disease. However,
      it is not known how this system changes in men and women with ageing. In healthy
      young and middle-aged subjects the following parameters were evaluated: total
      plasma cholesterol, triglycerides and HDL-cholesterol levels, deformability of
      erythrocytes, red blood cell and platelet aggregations, blood and plasma
      viscosity, neutrophils' cytosolic [Ca2+]i and microviscosity of the bilayer's
      total lipid phase and the annular near-protein zone of the membranes. Using
      intravital computer-associated microscopic system we investigated the
      microcirculation of bulbar conjunctiva. Oxygen transfer characteristics were
      measured with a Radiometer TCM2 monitor. It is evident from the data obtained
      that in men of middle age the total plasma cholesterol and triglyceride levels
      are higher in comparison with other groups. The rheological behavior of red blood
      cell and platelet aggregations in men differ from that in women. Neutrophils
      activation in healthy subjects was not recorded. Our results show that changes of
      the blood rheological properties of men 35-50 years old can lead to disturbances
      of the microcirculation.

PMID- 15258384
TI  - Hemorheological and antioxidant effects of Ascovertin in patients with sclerosis
      of cerebral arteries.
AB  - The clinical trials on 31 patients with arteriosclerosis and I-II stage
      discirculatory encephalopathy to assess an ability of Ascovertin to limit
      hemorheology abnormalities were carried out. In patients with discirculatory
      encephalopathy was a distinct increase in blood viscosity which was induced by
      disturbances of cell rheological factors: increase in aggregation of erythrocytes
      and decrease in their deformability were observed in comparison with indices in
      the group of healthy volunteers. No difference in plasma viscosity and fibrinogen
      was found. The treatment with Ascovertin in patients with discirculatory
      encephalopathy improved their attention, memory, mental performance, normalized
      sleep, releaved headache, decreased fatiquebility, led to the decrease in blood
      viscosity values, the reduction of pathological erythrocyte hyper aggregation and
      the improvement of erythrocyte deformability. We partly connect this clinical
      effect and hemorheology activity of Ascovertin with its antioxidant property-
      there was found impressive lipid peroxidation suppression. No significant changes
      in hemorheological and lipid peroxidation indices were observed in patients
      without Ascovertin.

PMID- 15258385
TI  - Lipid peroxidation in the erythrocytes under condition of their increased
      aggregation.
AB  - The aim of the present study was investigation of the lipid peroxidation changes
      within the erythrocytes under conditions of increased RBC aggregation. This
      latter was produced both in the in vitro and in vivo conditions by the addition
      of Dextran T-500. For the in vitro studies blood samples were taken from the
      cubital veins of 15 healthy subjects. During the in vivo studies 10 ml of the 10
      percent Dextran T-500 solution was administered intravenously in six chinchilla
      rabbits. Another six animals were treated with rheopolyglucyne. The RBC
      aggregation in blood was investigated with the "Georgian technique". The
      malondialdehyde (the end product of lipid peroxidation) was determined in all
      cases by its reaction with thiobarbituric acid. We found that in the in vitro
      conditions, as well as in the in vivo studies, the lipid peroxidation was
      significantly increased in the erythrocytes during the enhanced RBC aggregation
      induced by addition of Dextran T-500. Therefore we suppose that the elevated RBC
      aggregation cause an increase of cell's lipid peroxidation and it is possible to
      think that appropriate prooxidant: antioxidant balance is shifted toward the pro
      oxidants in the erythrocytes.

PMID- 15258386
TI  - Regional and systemic hemorheological disorders during feet diabetic gangrene.
AB  - We investigated the RBC aggregability in the patients with the foot diabetic
      gangrenes: in the venous blood samples taken from the damaged foot before its
      amputation, as well as from the cubital vein (the systemic circulation). The RBC
      aggregability was investigated with the "Georgian technique" that is sensitive
      and provided us with direct and quantitative data. We found that the RBC
      aggregability was higher by about 20%, in the blood flowing from the gangrenous
      tissue than in the systemic circulation. Therefore, the sources of the systemic
      hemorheological disorders were the primarily damaged tissues. Taking into account
      that the blood is uninterruptedly flowing and mixing together in the whole
      circulatory bed we conclude that in the systemic circulation a certain
      compensatory mechanism provide for a partial normalization of the blood
      rheological properties, since the RBC aggregability never reaches the level in
      the blood of the healthy people.

PMID- 15258387
TI  - Hemorheological disorders in the microcirculation following hemorrhage.
AB  - We analysed hemorheological disorders in the microcirculation of intestinal
      mesenterium of adult laboratory rats following massive exsanguinations when the
      mean arterial pressure dropped and then the hemorrhagic shock developed in the
      animals. The mesenteric microcirculation was analysed by the Texture Analysis
      System (Leitz, Wetzlar): (a) diameters of the afferent arterioles, capillaries,
      and efferent venules; (b) the blood flow velocity; (c) microvascular blood flow
      changes (during the RBC aggregation); (d) local microvascular hematocrit; and (e)
      the transformation of capillaries into plasmatic microvessels. During development
      of the hemorrhagic shock we found that the blood flow velocity decreased in all
      microvessels, there was an increased RBC aggregation which gradually enhanced in
      the mesenteric microvessels' lumen causing blood flow slowing down till
      appearance of stases. A part of the capillaries transformed into plasmatic
      vessels. Therefore the microcirculation demonstrated a significant decrease, this
      being related both to the lowered pressure gradient and to specific
      hemorheological disorders in the capillary networks.

PMID- 15258388
TI  - Effects of sample temperature on red blood cell shape in septic patients.
AB  - Several recent in vitro studies have observed that alterations in red blood cell
      (RBC) rheology depend on sample temperature. This possibility could limit the in
      vivo validity of the assessment of RBC shape. We investigated the effects of
      sample temperature on RBC shape estimated by flow cytometry in septic patients
      compared with those of volunteers. 0.5 ml of blood was placed at 4 degrees C,
      room temperature (20 degrees C) or at 37 degrees C. RBCs were analyzed at 30
      minutes (T30) by flow cytometry and results compared to baseline measures. With
      the flow cytometry technique, the RBC shape of healthy volunteers shows a bimodal
      distribution related to the biconcave form. On this histogram, we calculated the
      second Pearson coefficient of dissymmetry--PCD--representing the asymmetry of
      this histogram. At baseline, RBC PCD was increased in septic patients
      representing a more spherical shape compared to volunteers (-0.73+/-0.18 versus 
      0.95+/-0.05; p=0.007). For both groups, RBC shape estimated by the flow cytometry
      technique was not modified by the temperature of the sample. We conclude that
      estimation of RBC shape by flow cytometry is not influenced by the temperature of
      the sample. The present study validates the flow cytometry technique to assess
      RBC shape in vitro.

PMID- 15258389
TI  - Measurement of blood viscosity using a pressure-scanning capillary viscometer.
AB  - A newly designed pressure-scanning capillary viscometer is extended to measure
      the viscosity of whole blood over a range of shear rates without the use of
      anticoagulants in a clinical setting. In the present study, a single measurement
      of pressure variation with time replaces the flow rate and pressure drop
      measurements that are usually required for the operation of a capillary tube
      viscometer. Using a pressure transducer and capillary, we measured the variation
      of pressure flowing through capillary tube with respect to time, p(t), from which
      viscosity and the shear rate were mathematically calculated. For water and
      anticoagulant-added bloods, there was an excellent agreement found between the
      results from the pressure scanning capillary viscometer and those from a
      commercially available rotating viscometer. Also, the pressure-scanning capillary
      viscometer measured the viscosity of whole blood without heparin or EDTA. This
      new method overcomes the drawbacks of conventional viscometers in the measurement
      of whole blood viscosity. First, the pressure-scanning capillary viscometer can
      accurately and consistently measure the whole blood viscosity over a range of
      shear rates in less than 2 min without any anticoagulants. Second, this design
      provides simplicity (i.e., ease of operation, no moving parts, and disposable)
      and low cost.

PMID- 15258390
TI  - Generalized predictive equation for hematocrit by biological impedancemetry.
AB  - Bioelectrical impedancemetry (BIA) has been used to evaluate hemorheological
      parameters from whole body measurements. In a previous study, we have determined
      a set of predictive equations for hematocrit, whole blood viscosity and plasma
      viscosity in athletes. In another previous study, we also found other predictive
      equations in sedentary lean and obese subjects. This study aims at developing
      more generalized BIA-derived predictive equations for hemorheological parameters
      in both sedentary and trained individuals. 72 subjects, either athletes,
      sedentary obese or insulin resistant patients (33.57+/-1.60 yr; 80.81+/-2.06 kg;
      171.03+/-1.19 cm) were enrolled into the study. Body composition was assessed
      with a multifrequency bioelectrical impedancemeter (Dietosystem Human IM Scan)
      using low intensity at the following frequencies: 1, 5, 10, 50 and 100 kHz.
      Viscometric measurements were done at 1000 s(-1) with a falling ball viscosimeter
      (MT 90 Medicatest). Hematocrit (Hct) was measured with microcentrifuge.
      Hematocrit was correlated with impedance (Z) measurements at 50 kHz (r=-0.591,
      p=0.01). A generalized empirical predictive equation can thus be proposed. These
      findings further suggest that one can predict hematocrit in the general
      population with whole body electric properties.

PMID- 15258391
TI  - A device for biomechanical investigations of the viscoelastic characteristics of
      vital and artificial arterial segments.
AB  - The viscoelastic characteristics--modulus of elasticity, natural frequency,
      coefficient of viscosity and low-frequency resonance curve can be used as
      diagnostic indicators, at assessment of the direct effect of vasoactive drugs,
      and at selection of natural and artificial arterial prostheses. The aim of this
      work is a device for measurement of the viscoelastic characteristics of
      cylindrical segments of arteries in vitro and of arterial prostheses to be
      developed. The cylindrical segment is subjected to low frequency sinusoidal
      pulsations of the inner pressure. On the basis of the amplitude of the response
      oscillations of the wall, measured using the volume pulsations of the segment,
      the resonance curve is built so that the dynamic characteristics--modulus of
      elasticity, natural frequency, and coefficient of viscosity can be calculated.
      The living specimens are perfused with nutrition solution for keeping the quasi
      physiological conditions. In the same way, cylindrical segments of rubber and
      artificial human prostheses were investigated. The sensitivity and the accuracy
      of the device are given. The construction permits to keep the vitality of native
      animal's specimens when the measurements are carried out.

PMID- 15258392
TI  - Human bone marrow granulocyte-macrophageal colonies (GM-Cs) in vitro: myeloid
      cells in health and in cases of myeloid leukemia.
AB  - The morphological characteristics of granulocyte/macrophageal (GM-) colonies and
      clusters, obtained in vitro (in semi-solid agar cultures) from bone marrow
      hematopoietic myeloid progenitors pertain to leukocyte hemorheology of healthy
      persons and patients with myeloid leukemias. The morphological features of in
      vitro growing myeloid progenitors, granulocytes and macrophages of healthy
      persons differ in their cell size, shape and degree of differentiation from the
      cultivated marrow cells in cases of acute and chronic myeloid leukaemia. In this
      malignant disease, the rheological properties of leukocytes
      (granulocytes/macrophages) were found to provide diagnostic information. Further
      studies should be undertaken to examine whether the method could be useful in
      defining survival, prognosis and therapeutical approach in cases of myeloid
      leukemia.

PMID- 15258393
TI  - Electron density and electrostatic potential of KMnF3: a phase-transition study.
AB  - Three accurate X-ray diffraction experiments (Mo Kalpha, T = 190, 240 and 298 K)
      were carried out to track the temperature dependence of the electron density in
      the cubic perovskite potassium manganese trifluoride, KMnF3, from room
      temperature to just above that of the phase transition to the tetragonal
      structure (186 K), and to correlate the parameters of the critical points with
      the phase-transition mechanism. The data obtained were approximated by the Hansen
      Coppens multipole model expanded up to hexadecupoles; the anharmonicity of the
      atomic displacements up to the fourth level was considered. Topological analysis
      shows only two types of chemical bond at room temperature, Mn-F and K-F. However,
      at low temperature the K-F bonds blocking the rotation of the MnF6 octahedra are
      weakened and new Mn-K bonds are formed to keep the crystal structure from
      disintegrating. The Mn-K bonds become stronger as the temperature approaches 186
      K. This rearrangement of chemical bonds can be regarded as a precursor effect,
      which starts 50-60 degrees above the phase-transition temperature. The effective
      one-particle potential of the F atom has a single minimum at 298 K and four well
      separated minima (with a shift of 0.2 A from the equilibrium position towards the
      structural holes) at 190 K. Parameters of the critical points of the electron
      density indicate closed-shell type interactions between K-F and Mn-K pairs,
      whereas the Mn-F bond can be considered as an intermediate type. The topology of
      the electrostatic potentials is discussed as well.

PMID- 15258394
TI  - Variation of large-scale regularity in modulated structures of Ca2CoSi2O7 studied
      by a simulation method.
AB  - The period of two-dimensional modulation in Ca2CoSi2O7 varies with temperature (q
      = 0.285-1/3). The change in the modulated structure with the variation of q has
      been clarified by the construction of the structures using various q values and
      the modulation amplitudes determined at 293 K [q = 0.2913 (1), tetragonal]. The
      features of the modulated structures are characterized by the formation of CaO6
      polyhedra and the variable distribution of bundles along the c-axis, composed of
      four arrays of CaO6 polyhedra and an array of CoO4 tetrahedra. The formation of
      octagonal arrangements of the bundles is a typical feature of the structures in
      the incommensurate phase. Large-scale regularities with sizes much larger than
      the modulation wavelength are also formed in the structures.

PMID- 15258395
TI  - Structure of a high-pressure phase of vanadium pentoxide, beta-V2O5.
AB  - A high-pressure phase of vanadium pentoxide, denoted beta-V2O5, has been prepared
      at P = 6.0 GPa and T = 1073 K. The crystal structure of beta-V2O5 has been
      studied by X-ray and neutron powder diffraction, and high-resolution transmission
      electron microscopy. The V atoms are six-coordinated within distorted VO6
      octahedra. The structure is built up of quadruple units of edge-sharing VO6
      octahedra linked by sharing edges along [010] and mutually connected by sharing
      corners along [001]. This arrangement forms layers of V4O10 composition in planes
      parallel to (100). The layers are mutually held together by weak forces. beta
      V2O5 is metastable and transforms to alpha-V2O5 at 643-653 K under ambient
      pressure. Structural relationships between beta- and alpha-V2O5, and between beta
      V2O5 and B-Ta2O5-type structures are discussed. The high-pressure beta-V2O5 layer
      structure can be considered as the parent of a new series of vanadium oxide
      bronzes with cations intercalated between the layers.

PMID- 15258396
TI  - Li(3+delta)V6O13: a short-range-ordered lithium insertion mechanism.
AB  - The structures of Li3V6O13 and Li(3+delta)V6O13, delta approximately 0.3, have
      been determined by single-crystal X-ray diffraction. Both compounds have the
      space group C2/m, with very similar cell parameters. In Li3V6O13, the Li atoms
      are found in the Wyckoff positions 4(i) and 2(b) with multiplicities of four and
      two, respectively. Since Li3V6O13 exhibits no superstructure reflections, it is
      concluded that Li3V6O13 contains one disordered lithium ion in an otherwise
      ordered centrosymmetric structure. On inserting more lithium into the structure,
      the Li(3+delta)V6O13 phase is formed with the homogeneity range 0 < delta < 1. It
      is concluded that the site for the extra inserted lithium ion is closely coupled
      to the position of the disordered lithium ion in Li3V6O13. A mechanism for this
      behaviour and for the further formation of the Li6V6O13 end-phase in the LixV6O13
      system is proposed.

PMID- 15258397
TI  - Synchrotron X-ray and ab initio studies of beta-Si3N4.
AB  - Almost absorption- and extinction-free single-crystal synchrotron X-ray
      diffraction data were measured at 150, 200 and 295 K for beta-Si3N4, silicon
      nitride, at a wavelength of 0.7 A. The true symmetry of this material has been
      the subject of minor controversy for several decades. No compelling evidence
      favouring the low-symmetry P6(3) model was identified in this study.

PMID- 15258398
TI  - Structural manifestations of proton transfer in complexes of 2,6-dichlorophenols
      with pyridines.
AB  - DFT B3LYP/6-31G(d,p) calculations were performed to describe the proton transfer
      reaction pathway in the 2,6-dichlorophenolate of pyridine. The aim of these
      calculations was to establish the character of the dependence of the structure
      parameters on the proton transfer and comparing the results with known
      structures, e.g. the 2,6-dichloro-4-nitro- and pentachlorophenolates of
      pyridines. To make this comparison more reliable, the calculations were repeated
      with the use of a reaction-field correction with the Onsager radius and electric
      permittivity taken from the solid-state measurements. The calculations show that
      the second approach gives a better description of the structural modifications
      during the proton transfer.

PMID- 15258399
TI  - Bis(1-chloro-2,2,4,4-tetramethyl-3-oxocyclobutan-1-yl)pentasulfane: an occupancy
      modulated structure.
AB  - The title compound crystallizes in the space group P2(1)/n and may be described
      by a partial ordering of a 1:1 disordered P2(1)/a parent structure with the c
      axis halved. The pentasulfane chain completes a full turn of a helix, which gives
      molecules containing left- or right-handed helices similar spatial requirements
      and allows them to be interchanged. The structure can be redescribed as
      containing 0.732 (1) of an ordered P2(1)/n structure and 0.268 (1) of a 1:1
      disordered P2(1)/a structure, implying that 0.134 (1) of the molecule sites
      contain molecules of the opposite hand to that predicted by an ordered P2(1)/n
      structure. It is found that the average molecular position in the asymmetric unit
      is not the same for each component and that these structural differences must be
      recognized to obtain a satisfactory refinement.

PMID- 15258400
TI  - Analysis of the less common hydrogen bonds involving ester oxygen sp3 atoms as
      acceptors in the crystal structures of small organic molecules.
AB  - An analysis of hydrogen bonds involving ester Osp3 atoms as acceptors has been
      performed based on the data extracted from the Cambridge Structural Database
      [Allen (2002). Acta Cryst. B58, 380-388; version 5.25, November 2003], using the
      ConQuest package to evaluate the stereochemical and electronic properties of the
      acceptors. Evidence for the existence of this particular type of hydrogen bond
      and its structural function in crystal packing is presented. Using a cut-off
      limit on residual indices of R < 0.05 (for the structures with hydrogen bonds
      involving an oxygen as part of the donor group) and R < 0.085 (for nitrogen as
      part of the donor group), 230 structures out of the total CSD entries of 298,100
      were found to contain hydrogen bonds with the ester Osp3 atoms as acceptors. The
      hydrogen-bond donors include water molecules, hydroxyl groups, primary and
      secondary amines and, in a few cases, imino groups. Four modes of the
      participation of the ester Osp3 atoms in hydrogen bonding are detected: as a
      single acceptor, as a double acceptor, as a single acceptor of a H atom involved
      in an intermolecular bifurcated hydrogen bond, and as a shared acceptor function
      with the ester Osp2 atom in a bifurcated hydrogen bond. The role of such directed
      noncovalent interactions in crystal packing is demonstrated by a small gallery of
      selected structures.

PMID- 15258401
TI  - Rigid backbone moiety of KNI-272, a highly selective HIV protease inhibitor:
      methanol, acetone and dimethylsulfoxide solvated forms of 3-[3-benzyl-2-hydroxy-9
      (isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4,7-diazanonanoyl]-N-tert
      butyl-1,3-thiazolidine-4-carboxamide.
AB  - When crystals of kynostatin (KNI)-272, a highly selective HIV protease inhibitor
      containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid],
      were grown in three different solvent systems (methanol, acetone and
      dimethylsulfoxide solutions), the local conformations around the
      hydroxymethylcarbonyl (HMC) moiety, which mimics the structure of the transition
      state, were similar in all three forms. The peptide backbones were slightly bent,
      but their structures differed from typical sheets, turns or helixes. Although the
      isoquinoline ring at the N-terminal showed conformational variations, a
      remarkable similarity was observed in the C-terminal region, including the HMC
      moiety. Moreover, the conformational characteristics of the uncomplexed forms
      resembled those of the inhibitor within the KNI-272-HIV protease complex. This
      suggests that the structure of the C-terminal region of KNI-272 is rigid or very
      stable.

PMID- 15258402
TI  - 2-Hydroxyisophthalic acid: hydrogen-bonding patterns in the monohydrate and the
      tetraphenylphosphonium salt. An instance of dramatic acidity enhancement by
      symmetric, internally hydrogen-bonded anion stabilization.
AB  - The monohydrate of the title phenolic diacid (C8H6O5.H2O, 2-hydroxybenzene-1,3
      dioic acid or 3-carboxysalicylic acid) adopts a planar conformation, with the
      phenol hydrogen internally hydrogen-bonded to the carbonyl of one highly ordered
      carboxyl, which, in turn, donates a hydrogen bond to the oxygen of water. The
      second carboxyl is disordered and hydrogen-bonded both to water and to the
      disordered carboxyl of a centrosymmetrically related neighbor in a static
      disorder arrangement extending over two full asymmetric units. The water accepts
      either one or two hydrogen bonds and donates a long bifurcated hydrogen bond
      shared equally by O atoms of the phenol and the disordered carboxyl. The hydrogen
      bonding includes no standard carboxyl pairing and is entirely two-dimensional.
      The resulting planar ribbons stack translationally at a distance of 3.413 (8) A,
      in an offset arrangement having non-translational interplanar distances of 0.821
      (5) and 2.592 (6) A. This structure is compared with two previously reported for
      this compound. The title compound forms a monoanion, whose tetraphenylphosphonium
      salt is described (C32H25O5P, tetraphenylphosphonium 2,6-dicarboxyphenolate,
      tetraphenylphosphonium 2-oxidoisophthalic acid or tetraphenylphosphonium 3
      carboxysalicylate). The phenol oxygen is the site of formal negative charge on
      the anion, which is stabilized in a planar arrangement by symmetrical hydrogen
      bonds from both ortho-carboxyl groups. The energetics of this arrangement, the
      phenol and carboxyl acidities, and factors affecting those acidities and
      providing anion stabilization are discussed.

PMID- 15258403
TI  - Sizes of molecules in organic crystals: the Voronoi-Dirichlet approach.
AB  - The sizes of more than 100,000 molecules in organic crystals have been assessed
      as the volumes of molecular Voronoi-Dirichlet polyhedra. The average molecular
      volumes for all crystals are shown to be nearly equal to the corresponding values
      in homomolecular (consisting of identical molecules) crystals. The validity of
      the Voronoi-Dirichlet approach in determining molecular sizes is substantiated
      and the reasons for the variations in the molecular volumes are discussed. It is
      shown that a molecule increases its volume if it is surrounded by a good deal of
      high-row (i.e. an element with more than ten protons) atoms or if there is
      disorder in the crystal structure.

PMID- 15258404
TI  - Ab initio structure determination of the hygroscopic anhydrous form of alpha
      lactose by powder X-ray diffraction.
AB  - Annealing of alpha-lactose monohydrate at 408 K yielded a mixture of this
      compound with hygroscopic anhydrous alpha-lactose. A powder X-ray diffraction
      pattern of this mixture was recorded at room temperature. The starting structural
      model of hygroscopic alpha-lactose was found by a Monte Carlo simulated-annealing
      method. The final structure was obtained through Rietveld refinements, with soft
      restraints on interatomic bond lengths and bond angles, and crystalline energy
      minimization to locate the H atoms of the hydroxy groups. The crystalline
      cohesion is achieved by networks of O-H...O hydrogen bonds that differ from those
      of the monohydrate phase. The width of the Bragg peaks is interpreted by a
      phenomenological microstructural approach in terms of isotropic size effects and
      anisotropic strain effects.

PMID- 15258405
TI  - Supramolecular structures of substituted alpha,alpha'-trehalose derivatives.
AB  - The structures of five substituted alpha,alpha'-trehalose trehalose derivatives
      have been determined, and these are compared with those of four previously
      published analogues. In 2,2',3,3',4,4'-hexaacetato-6,6'-bis-O-methylsulfonyl
      alpha,alpha'-trehalose, C26H38O21S2, where the molecules lie across twofold
      rotation axes in the space group C2, a single C-H...O=S hydrogen bond links the
      molecules into sheets. 2,2',3,3',4,4'-Hexaacetato-6,6'-bis-O-(4-toluenesulfonyl)
      alpha,alpha'-trehalose, C38H46O21S2, crystallizes with Z' = 2 in the space group
      P2(1)2(1)2(1) and a combination of three C-H...O hydrogen bonds, each having a
      carbonyl O atom as an acceptor, and a C-H...pi(arene) hydrogen bond link the
      molecules into a three-dimensional framework. 2,2',3,3',4,4'-Hexaacetato-6,6'
      diazido-alpha,alpha'-trehalose, C24H32N6O15, crystallizes as a partial ethanol
      solvate and three C-H...O hydrogen bonds link the substituted trehalose molecules
      into a three-dimensional framework. In 2,2',3,3'-tetraacetato-6,6'-bis(N
      acetylamino)-alpha,alpha'-trehalose dihydrate, C24H36N2O15...2H2O, the
      substituted trehalose molecules lie across twofold rotation axes in the space
      group P2(1)2(1)2 and a three-dimensional framework is generated by the
      combination of O-H...O and N-H...O hydrogen bonds. The diaminotrehalose molecules
      in 6,6'-diamino-alpha,alpha'-trehalose dihydrate, C12H24N2O9...2(H2O), lie across
      twofold rotation axes in the space group P4(3)2(1)2: a single O-H...N hydrogen
      bond links the trehalose molecules into sheets, which are linked into a three
      dimensional framework by O-H...O hydrogen bonds.

PMID- 15258406
TI  - Isomeric iodo-N-(nitrobenzyl)anilines: interplay of hard and soft hydrogen bonds,
      iodo...nitro interactions and aromatic pi...pi stacking interactions.
AB  - Molecules of 2-iodo-N-(4-nitrobenzyl)aniline, 4-O2NC6H4CH2NHC6H4I-2' (1) are
      linked into chains by C-H...O hydrogen bonds. In the isomeric compound 3-iodo-N
      (4-nitrobenzyl)aniline (2) a combination of N-H...O and C-H...O hydrogen bonds
      and iodo...nitro and aromatic pi...pi stacking interactions links the molecules
      into a three-dimensional framework structure. The two-dimensional supramolecular
      structure of 4-iodo-N-(4-nitrobenzyl)aniline (6) is built from a combination of C
      H...O and N-H...pi(arene) hydrogen bonds and aromatic pi...pi stacking
      interactions. 2-Iodo-N-(2-nitrobenzyl)aniline (7) crystallizes with two molecules
      in the asymmetric unit and these molecules are linked into ladders by a
      combination of N-H...O and C-H...O hydrogen bonds and iodo...nitro and aromatic
      pi...pi stacking interactions. Comparisons are made between the supramolecular
      structures of these compounds and those of other isomers, in terms both of the
      types of direction-specific intermolecular interactions exhibited and the
      dimensionality of the resulting supramolecular structures.

PMID- 15258407
TI  - Structural features controlling the binding of beta-carbolines to the
      benzodiazepine receptor.
AB  - Beta-carbolines are a class of drug which can interact with a high affinity with
      the benzodiazepine (BDZ) binding site of the GABAA receptor. The present paper,
      aimed at obtaining a deeper insight into the structure-properties relationships
      of this class of molecules, reports the crystal structures of four beta
      carbolines: ZK93423 (3-carboethoxy-4-methoxymethyl-6-benzyloxy-beta-carboline),
      ZK91296 (3-carboethoxy-4-methoxymethyl-5-benzyloxy-beta-carboline), FG7142 (N
      methyl-3-carbamoyl-beta-carboline) and the low-affinity ligand harmine
      hydrochloride (1-methyl-7-methoxy-beta-carboline). This set of structural data is
      completed by the X-ray structures of other carbolines of known biological
      activity retrieved from the Cambridge Crystallographic Database and by the
      structures of beta-CCE (3-carboethoxy-beta-carboline), 6-PBC (3-carboethoxy-4
      methoxymethyl-6-isopropoxy-beta-carboline), PRCC (3-isopropoxy-beta-carboline)
      and ZK93426 (3-carboethoxy-4-methyl-5-isopropoxy-beta-carboline), which have been
      obtained by molecular-mechanics simulations. The structural features of all these
      molecules have been compared according to the stereochemical model we proposed in
      1987. The structural comparison is integrated by the Free-Wilson analysis on 32
      beta-carbolines of known binding affinity data.

PMID- 15258409
TI  - Diabetes mellitus in Tropical Chronic Pancreatitis Is Not Just a Secondary Type
      of Diabetes.
AB  - AIMS: In chronic calcific pancreatitis of the tropics, etiology and relationship
      to developing diabetes mellitus are unknown. Some consider these cases a
      straightforward secondary type of diabetes, while others suggest selective beta
      cell impairment. Testing pancreatic function, we investigated whether selective
      beta-cell impairment triggers diabetes associated with tropical pancreatitis.
      METHODS: At a Bangladeshi research institute, 8 chronic tropical pancreatitis and
      no diabetes mellitus subjects, 14 fibrocalculous pancreatic diabetics and 27
      matched healthy controls underwent arginine (endocrine pancreatic function) and
      secretin (exocrine pancreatic function assessment) stimulation tests. RESULTS:
      All patients with clinically-diagnosed, chronic pancreatitis demonstrated
      pronounced exocrine pancreatic dysfunction with beta-cell functioning differing
      significantly between the two groups. Compared to controls, patients having
      tropical pancreatitis and no diabetes showed normal plasma C-peptide values at
      baseline and after arginine stimulation, while fibrocalculous pancreatic
      diabetics demonstrated a typical diabetic pattern for plasma C-peptide levels. In
      contrast, pancreatic alpha-cell functioning (glucagon response to arginine) was
      preserved in both pancreatitis groups. CONCLUSION: A preserved pancreatic alpha
      cell function in diabetics with advanced chronic pancreatitis of the tropics
      supports the concept of two different pathogenic mechanisms, one eliciting
      chronic pancreatitis and the other selective pancreatic beta-cell impairment and
      subsequent diabetes mellitus.

PMID- 15258410
TI  - Uveitis: a potentially blinding disease.
AB  - Uveitis (intraocular inflammation) is a potentially blinding group of, probably
      autoimmune, conditions predominantly occurring in the working age group. Although
      the aetiology is unknown in most cases, many patients have an associated
      underlying systemic disease. Central vision loss, in the form of cystoid macular
      oedema, is the commonest type of visual impairment. Although historical incidence
      and prevalence data exists, little is known about the degree of vision loss
      experienced, and the social and financial consequences of having temporary or
      permanent visual impairment in this age group. The literature is also full of
      uncontrolled studies and case reports of different modalities of drug therapy for
      uveitis. This article attempts to raise the awareness of uveitis as an important
      sight-threatening group of conditions by highlighting the paucity of evidence
      based data on epidemiological, quality of life, socioeconomic, and therapeutic
      aspects.

PMID- 15258411
TI  - Ocular blood flow velocity determined by color Doppler imaging in diabetic
      retinopathy.
AB  - PURPOSE: To measure and investigate changes of blood flow velocity by color
      Doppler imaging in the ophthalmic artery (OA), central retinal artery (CRA) and
      short posterior ciliary arteries (PCA) in diabetic retinopathy (DR) and to
      compare the results with those in healthy control subjects. METHODS: In this
      investigation we included 44 eyes of 44 diabetic patients with different stages
      of DR forming group NPDR (11 eyes with mild and 11 eyes with moderate
      nonproliferative DR) and group SNPDR/PDR (19 eyes with severe nonproliferative
      and 3 eyes with proliferative DR) and 22 eyes of 22 healthy age- and sex-matched
      subjects forming control group HC. With color Doppler imaging we measured the
      peak systolic velocity (PSV, cm/s) and end-diastolic velocity (EDV, cm/s) of
      blood flow in the OA, CRA and PCA. The resistance index of each vessel was then
      calculated. Statistical analysis comparing the results of groups NPDR, SNPDR/PDR
      and HC was carried out. Statistical significance was set at p < 0.05. RESULTS:
      There was a statistically significant increase in PSV in the OA in group
      SNPDR/PDR compared with group HC (35.71 +/- 6.90 vs. 31.45 +/- 4.32 cm/s; mean +/
      SD). There was a statistically significant decrease in PSV in the CRA in group
      NPDR compared with group HC (8.50 +/- 1.62 vs. 10.61 +/- 1.75 cm/s; mean +/- SD)
      and in group SNPDR/PDR compared with group HC (7.34 +/- 1.78 vs. 10.61 +/- 1.75
      cm/s; mean +/- SD), also there was a statistically significant decrease in EDV in
      group SNPDR/PDR compared with group HC (2.05 +/- 0.53 vs. 3.00 +/- 0.81 cm/s;
      mean +/- SD). A statistically significant decrease in EDV in the PCA in group
      SNPDR/PDR compared with group HC (2.95 +/- 1.04 vs. 3.95 +/- 0.98 cm/s; mean +/-
      SD) was found, also there was a statistically significant increase in the
      resistance index in group SNPDR/PDR compared with group NPDR (0.72 +/- 0.05 vs.
      0.67 +/- 0.07; mean +/- SD) and in group SNPDR/PDR compared with group HC (0.72
      +/- 0.05 vs. 0.67 +/- 0.05; mean +/- SD). CONCLUSIONS: In this investigation,
      color Doppler imaging was used to determine significant changes of blood flow
      velocity in the OA, CRA and PCA in DR compared with healthy control subjects and
      the changes of blood flow velocity become further significant considering the
      progression of DR. This points to the presence of circulatory changes in the OA,
      CRA and PCA in diabetic patients with DR.

PMID- 15258412
TI  - Staining of intraocular lenses with various dyes: a study of digital image
      analysis.
AB  - PURPOSE: To evaluate the interaction of various intraocular lens (IOL) materials
      with commonly used dyes. MATERIALS AND METHODS: One IOL of each of the five
      groups (polymethylmethacrylate, silicone, three-piece hydrophobic acrylic, single
      piece hydrophobic acrylic and single-piece hydrophilic acrylic) was bathed in
      trypan blue 0.1%, fluorescein sodium 2% and indocyanine green (ICG) 0.5% for 15
      min. Digital photographs of the IOLs were obtained prior to bathing and after the
      15-min bath in each dye. The same IOLs were immersed in the same dye for another
      15 min and digital images were reobtained to depict the 30-min dye uptake. New
      IOLs from the group that exhibited visible colour change after the 15-min bath
      were then bathed in twofold dilution and if there was still visible dye uptake,
      fourfold dilution was performed, repeating the 15-min bath and digital
      photography. The images were then processed using Adobe Photoshop 5.1 to get mean
      luminosity and red-green-blue values. These values were compared between the
      groups and the undyed control. Also, dye washout was observed in serum-containing
      vials. RESULTS: None of the polymethylmethacrylate, silicone and hydrophobic
      acrylic IOLs were stained with the dyes used. The only IOL material that changed
      colour was hydrophilic acrylic and did so with all dyes. The most marked colour
      change was with fluorescein sodium 2%, the least was with trypan blue 0.05%.
      Twofold dilution of trypan blue and fourfold dilutions of fluorescein sodium and
      ICG still stained the hydrophilic acrylic IOL; however, fourfold dilution of
      trypan blue did not cause a significant colour change. Trypan blue washed out
      within 6 h, while the IOL stained with ICG remained stained for longer than 24 h.
      COMMENT: Hydrophilic acrylic IOLs should be used with caution together with dyes
      since this material demonstrates marked dye uptake and washout may also take some
      time.

PMID- 15258413
TI  - Triamcinolone acetonide facilitates removal of the epiretinal membrane and
      separation of the residual vitreous cortex in highly myopic eyes with retinal
      detachment due to a macular hole.
AB  - PURPOSE: To study the usefulness of intravitreal triamcinolone acetonide
      injection during vitrectomy in highly myopic eyes with retinal detachment due to
      a macular hole. METHODS: Pars plana vitrectomy was performed in 6 patients with
      retinal detachment resulting from a highly myopic eye with a macular hole. After
      separation of the posterior hyaloid and removal of any visible epiretinal
      membrane, triamcinolone acetonide was injected over the posterior pole. Excised
      specimens were evaluated by transmission electron microscopy. RESULTS: Upon
      injection of triamcinolone acetonide, the entire epiretinal membrane and residual
      vitreous cortex could be visualized in all patients. The epiretinal membrane and
      residual posterior vitreous cortex were completely removed. Successful
      reattachment was performed without retinal damage in all cases. Electron
      microscopy revealed a cellular epiretinal membrane within a collagenous matrix
      lining the smooth internal surface of the internal limiting membrane. No
      complications related to the use of triamcinolone acetonide were encountered.
      CONCLUSION: Intraoperative visualization of the epiretinal membrane and residual
      posterior vitreous cortex with triamcinolone acetonide was found to be a useful
      adjunct to vitrectomy. Using triamcinolone acetonide during vitrectomy may
      facilitate both removal of the epiretinal membrane around the macular hole and
      separation of the residual vitreous cortex from the retina in highly myopic eyes
      with retinal detachment.

PMID- 15258414
TI  - The effects of hormone replacement therapy on ocular surface and tear function
      tests in postmenopausal women.
AB  - PURPOSE: To prospectively investigate the impact of various hormone replacement
      therapies (HRT) on ocular surface and tear function tests. METHODS: A total of 70
      women in the postmenopausal period were enrolled in the study. The groups
      consisted of 16 women who were not on HRT (group 1), 29 women who were on HRT
      with tibolone (group 2) and 25 women who received estradiol plus
      medroxyprogesterone acetate treatment (group 3). All patients underwent tear film
      break-up time (TFBUT), Schirmer's test and conjunctiva cytology at the time of
      enrollment and at 6 months' follow-up. RESULTS: Patients in group 2 showed
      improved Schirmer's test and TFBUT results (p < 0.001); however, no significant
      changes occurred in group 1 and group 3 patients (p > 0.05). Conjunctival
      cytology scores did not differ at the time of enrollment and at 6 months' follow
      up in all groups. CONCLUSIONS: This is the first comparative clinical study on
      the effects of tibolone and estradiol plus medroxyprogesterone acetate on ocular
      surface and tear function tests. HRT with tibolone seems to improve tear function
      tests in postmenopausal women.

PMID- 15258415
TI  - Levels of human tissue kallikrein in the vitreous fluid of patients with severe
      proliferative diabetic retinopathy.
AB  - The aim of this study was to determine the levels of human tissue kallikrein in
      the vitreous fluid of patients with severe proliferative diabetic retinopathy
      (PDR). Tissue kallikrein levels were measured using a specific ELISA (range: 0.4
      25 ng/ml) in 7 vitreous fluids from eyes with severe PDR. Seven vitreous samples
      from eyes which underwent vitrectomy because of rhegmatogenous retinal detachment
      served as non-PDR controls. Enzymatic activity was also tested by an amidolytic
      assay using a chromogenic substrate. In the PDR patients, vitreous tissue
      kallikrein was <0.4 ng/ml (5 eyes) or very low (0.52 and 0.58 ng/ml). Vitreous
      tissue kallikrein was <0.4 ng/ml in all non-PDR controls. These results were
      confirmed by the amidolytic test. Results suggest that vitreous tissue kallikrein
      probably plays either a secondary or no role in the pathogenesis of PDR.

PMID- 15258416
TI  - Deep sclerectomy with various implants: an experimental and histopathologic study
      in a rabbit model.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effectiveness of various implants
      used in experimental deep sclerectomy and to report tissue reactions developed to
      these implants histopathologically. MATERIALS AND METHODS: Forty eyes of 40 New
      Zealand white albino rabbits underwent deep sclerectomy with various implants.
      The rabbits were divided into four groups; each consisted of 10 eyes. Deep
      sclerectomy was performed using copolymer materials in group 1, silicone
      materials in group 2 and chromic catgut suture in group 3. No implants were used
      in the control group (group 4). Clinical and histopathological examinations were
      performed to investigate the effectiveness of implants. RESULTS: Mean
      preoperative intraocular pressure (IOP) was 14.4 +/- 1.6 mm Hg in group 1, 14.5
      +/- 1.8 mm Hg in group 2, 13.8 +/- 1.5 mm Hg in group 3 and 14.5 +/- 1.2 mm Hg in
      group 4. The final postoperative IOPs were 10.7 +/- 0.9, 10.6 +/- 0.8, 13.5 +/-
      1.0, and 14.5 +/- 1.4 mm Hg, respectively. At 2 months, the decrease in IOPs from
      baseline and the persistence of the filtering bleb were significantly marked in
      group 1 and group 2 (p < 0.001). Histopathological evaluation revealed that
      copolymer and silicone materials formed a smooth and regular intrascleral space.
      There were no foreign body reaction, tissue destruction or fibrosis in group 1
      and group 2, but chromic catgut sutures caused severe fibrosis and inflammatory
      reaction in group 3. Mean histopathologic score of group 1, group 2, group 3 and
      group 4 was 0.7 +/- 0.5, 0.8 +/- 0.5, 2.4 +/- 0.6, and 0.1 +/- 0.3, respectively.
      CONCLUSION: Copolymer or silicone materials may increase the success rate of
      surgery by maintenance of a large and regular intrascleral space after deep
      sclerectomy and prevention of collapse of the flap.

PMID- 15258417
TI  - Pars plana vitrectomy without long-acting gas tamponade for primary
      rhegmatogenous retinal detachment.
AB  - PURPOSE: To report the anatomical and visual results of primary pars plana
      vitrectomy (PPV) without long-acting gas tamponade to repair primary
      rhegmatogenous retinal detachments (RRDs). METHODS: Twenty-seven consecutive
      patients (27 eyes) with peripheral retinal tears and new RRDs were treated
      according to the surgical protocol. Patients underwent PPV with fluid-air
      exchange and endolaser treatment to repair the RRD. Neither long-acting gas nor
      silicone oil tamponade was combined with PPV. All patients were followed from 6
      to 26 months with an average follow-up of 11 months. Reattachment of the retina
      and visual outcome were compared to the results of previously published studies.
      RESULTS: Reattachment was achieved in 24 of 27 eyes (89%) with a single
      operation, and in all 27 (100%) eyes, the retina was ultimately reattached with
      subsequent operations. The median initial visual acuity was 0.4, and the median
      final visual acuity was 1.0. CONCLUSIONS: Primary PPV with fluid-air exchange
      alone and laser treatment is a safe, effective method for the repair of primary
      retinal detachments. The anatomical reattachment rate and the visual acuity
      obtained with this technique appear to be at least as good as those reported in
      the literature for primary PPV combined with long-acting gas tamponade.

PMID- 15258418
TI  - Eyelid tumors in children: a clinicopathologic study of a 10-year review in
      southern Taiwan.
AB  - PURPOSE: To describe the clinical and histopathologic characteristics of eyelid
      tumors in children in southern Taiwan. METHODS: Patients younger than 17 years
      old with histologically confirmed eyelid tumors treated at Chang Gung Memorial
      Hospital (Kaohsiung) during 1991-2000 were subjected to a retrospective analysis.
      Patients with inflammation, granulation, hordeolum, chalazion and orbital or
      conjunctival extension were excluded. RESULTS: Totally, 78 patients (46 boys and
      31 girls) with eyelid tumors were included. The 4 most common tumors, in order of
      frequency, were epidermal cysts (23.1%), dermoid cysts (17.9%), squamous cell
      papillomas (11.5%), and compound nevi (9%). Recurrence was noted in only 1 case
      (of a ductal cyst) after surgical excision during the 3-year follow-up period.
      CONCLUSIONS: Epithelial tumors and dermoid cysts are the most common eyelid
      tumors of children in southern Taiwan. Surgical excision produced good results.
      Malignant eyelid tumors are rare in children.

PMID- 15258419
TI  - Influence of indocyanine green staining on the biomechanical strength of porcine
      internal limiting membrane.
AB  - PURPOSE: Indocyanine green (ICG) has recently been introduced to stain
      selectively the internal limiting membrane (ILM) of the retina for ILM peeling.
      The aim of the present in vitro study was to examine the effect of ICG staining
      on the biomechanical properties of porcine ILM. METHODS: Two parallel 10 x 7 mm
      strips of central retina were prepared from each of the 40 porcine eyes. 0.005%
      ICG staining combined with white light illumination for 3 min was performed.
      Unstained, nonilluminated and 0.1% glutaraldehyde-treated specimens were used as
      controls. Biomechanical-force elongation measurements were performed using an
      automated material tester. The absorption spectrum of the ICG solution and the
      emission spectrum of the light source was measured. RESULTS: After ICG staining
      of the retina combined with 3 min of illumination, a significant increase in
      ultimate force by 45% and a decrease in ultimate elongation by 24% was found.
      Without light exposure, there was no such effect, suggesting a light-dependent
      process. After 30 min of 0.1% glutaraldehyde treatment, there was an increase in
      ultimate force by 107% and a decrease in ultimate elongation by 66.6%. The
      absorption spectrum of the light source was continuous in the range from 400 to
      800 nm including the absorption peak of ICG at 700 nm. CONCLUSIONS: ICG staining
      of the retina including the ILM causes a significant increase in the
      biomechanical stiffness thereby facilitating ILM peeling. The effect is due to a
      photosensitizing effect of ICG leading to collagen cross-linking.

PMID- 15258420
TI  - Bilateral central retinal vein occlusion associated with multiple myeloma.
AB  - PURPOSE: To report a case of simultaneous bilateral central retinal vein
      occlusion (CRVO) associated with multiple myeloma. METHODS: A 65-year-old woman
      had sudden, painless loss of vision in both eyes for 20 days. Ophthalmologic
      examination revealed bilateral CRVO. Appropriate medical workup was conducted,
      and multiple myeloma was diagnosed as the underlying cause. RESULTS: Clinical
      support and chemotherapy effectively controlled paraprotein production, leading
      to improvement of both systemic and ocular alterations. CONCLUSIONS: Many
      conditions have been noted to be associated with CRVO. Based on a Medline search,
      this is the first report of simultaneous bilateral CRVO as the first
      manifestation of multiple myeloma, illustrating the need for a primary care
      ophthalmologist to be involved in the basic assessment for associated underlying
      diseases in retinal disorders.

PMID- 15258421
TI  - Early and late assessment of internal drainage of chronic dacryocystitis.

PMID- 15258423
TI  - Resistance of cultured human skin fibroblasts from old and young donors to
      oxidative stress and their glutathione peroxidase activity.
AB  - BACKGROUND: It has been suggested that oxidative stress is involved in the aging
      process and that the resistance of animals to oxidative stress may decrease with
      advancing aging. However, there are only a limited number of reports of studies
      on the relationship between aging and resistance to oxidative stress. OBJECTIVE:
      The aim of this work is to examine the relationship between the resistance of
      human skin fibroblasts to oxidative stress and donor age, and the relevance of
      antioxidant enzyme activities to this resistance. METHODS: Percent cell survival
      was determined by the trypan blue exclusion test and the neutral red method.
      Superoxide dismutase activity was assayed by the method of Oyanagi, catalase
      activity by the method of Aebi, and glutathione peroxidase activity by the method
      of Flohe and Gunzler. Reduced glutathione concentration was measured by the
      method of Griffith. Antioxidant enzyme mRNA levels were estimated by reverse
      transcription polymerase chain reactions (RT-PCR). RESULTS: The percent survivals
      of cultured human skin fibroblasts, derived from young and old donors (referred
      to as young and old cells, respectively), under oxidative stress from hydrogen
      peroxide, linoleic acid hydroperoxide, or ultraviolet light B were examined. Old
      cells were more resistant to such oxidative stress than young cells. The activity
      of glutathione peroxidase was higher by 46.1% in old cells than in young cells,
      although there was no difference between their relative glutathione peroxidase
      mRNA levels. Further, there was no difference between their activities of
      copper/zinc superoxide dismutase, manganese superoxide dismutase, or catalase.
      However, the relative mRNA levels of copper/zinc superoxide dismutase and
      manganese superoxide dismutase were lower by 13.9 and 20.9% in old cells than in
      young cells, respectively, while there was no difference between the levels of
      catalase. CONCLUSIONS: These results suggest that old cells are more resistant to
      oxidative stress than young cells, presumably because of an increase in cellular
      glutathione peroxidase activity.

PMID- 15258424
TI  - Long-term influence of perinatal asphyxia on the social behavior in aging rats.
AB  - BACKGROUND: Various groups have been addressing the question of whether perinatal
      asphyxia (PA) affects the behavior of young animals, but no information is
      available on long-term effects of PA on the behavior in aged rats, although it
      has been postulated that PA may lead to neurological and psychiatric deficits in
      adult life. OBJECTIVE: We, therefore, decided to study the effects of PA on
      social and anxiety-related behaviors in 2-year-old rats, using a noninvasive
      animal model resembling the clinical situation. METHODS: For the behavioral
      studies, the open-field test, the elevated plus-maze test, and a social
      interaction test in pairs were performed. Magnetic resonance imaging of the brain
      was selected to rule out neuropathological changes due to the aging process per
      se, as well as asphyxia-induced pathologies in the brain areas known to play an
      important role in the modulation of behavior. RESULTS: The social interaction
      test revealed a statistically significant increase in the number of social
      grooming episodes and the time spent running alone, whereas the numbers of social
      sniffing and fighting episodes and the time spent running together were decreased
      in the asphyxiated group. The elevated plus- maze test revealed a higher presence
      of entries into the closed arm. Furthermore, sniffing and self-grooming episodes
      were significantly increased in the asphyxiated group. CONCLUSIONS: We found a
      significantly decreased social aggressiveness and an increased social contact
      behavior as well as increased anxiety levels in the asphyxiated animals. The
      present findings may provide important information on the long-term behavioral
      sequelae of PA in the aged individual.

PMID- 15258425
TI  - Impaired lipid metabolism in aged mice as revealed by fasting-induced expression
      of apolipoprotein mRNAs in the liver and changes in serum lipids.
AB  - BACKGROUND: Changes in apolipoprotein (Apo) metabolism can cause an increased
      incidence of diseases such as cardiovascular disorders and diabetes with
      advancing age. Limited reports are available on this topic, however. OBJECTIVE:
      To investigate age-related changes in mobilization of stored lipid, we studied
      the effects of fasting on the gene expression of Apos in the liver as well as
      serum triglyceride (TG) and cholesterol levels in the serum. METHODS: Using young
      (6- to 8-month-old) and old (24- to 28-month-old) fasted and re-fed mice,
      Northern blots of hepatic mRNAs for Apos A-I, A-IV, C-II, C-III, and liver-type
      fatty acid-binding protein and HPLC analyses of serum lipids were conducted.
      RESULTS: Fasting induced 4- and 20-fold increases in the mRNA of Apo C-II and A
      IV, respectively, in young mice while only 1.1- and 7-fold increases,
      respectively, were detected in old mice. In contrast, the Apo C-III gene
      expression was significantly reduced by fasting in the young mice but the
      reduction was small in the old. In view of the stimulating effect of Apo C-II and
      A-IV and the inhibiting effect of C-III on lipoprotein lipase (LPL), these
      findings suggest that the fasting-induced activation of LPL may be considerably
      decreased in old mice. The amount of TG in very low-density lipoprotein (VLDL), a
      major form of the transport of TG to peripheral tissues, was significantly
      greater in the young than in the old mice. Despite possible activation of LPL by
      fasting, the amount of TG in VLDL, a major form of the transport of TG to
      peripheral tissues, was significantly greater in the young mice than in the old.
      It is indicated that the synthesis of VLDL in the liver is high in the young but
      low in the old mice, which also may be true for the rate of transport of TG.
      CONCLUSION: The present findings suggest that mobilization of lipids is impaired
      in old animals due to decreased gene expression of Apos, possibly leading in the
      long run to excessive lipid accumulation in tissues such as the liver, adipose
      tissues and blood vessels even in normal feeding, and resulting in an increased
      incidence of age-related diseases.

PMID- 15258426
TI  - Different C-reactive protein kinetics in post-operative hip-fractured geriatric
      patients with and without complications.
AB  - BACKGROUND: Hip fracture is a frequent injury in the elderly, and is associated
      with a high incidence of functional impairment, complications and mortality.
      OBJECTIVE: To determine kinetics of C-reactive protein (CRP), fibrinogen and
      erythrocyte sedimentation rate (ESR) in hip-fractured patients over a 1-month
      post-operative period; to examine the relationship of these parameters to
      cognition, operation type, post-operational complications, functional level 1
      month post-operatively and 6-month mortality. METHODS AND SUBJECTS: 32 aged
      patients operated on for hip fracture were prospectively followed-up for 6
      months. Fracture, type of operation and anesthetic risk were recorded. Cognition
      was evaluated by the Mini-Mental State Examination and pre-fracture functional
      level evaluated by the Katz Index of ADL. Follow-up included complications,
      mortality and functional outcome. CRP, fibrinogen and ESR were assessed during
      the first 10 h post-fracture; 48-60 h, and 7 and 30 days post-operatively,
      respectively. RESULTS: Only CRP kinetics were found to differ in patients with
      complications vs. those without, as a group (p = 0.006), and in patients
      suffering infections, delirium and cardiovascular complication vs. patients with
      no complications (p = 0.06, 0.03, 0.02, respectively). Mean (+/-SEM) CRP 48-60 h
      post-operatively was 20.9 +/- 2.1 and 13.1 +/- 1.6 mg/dl in complicated and
      uncomplicated patients, respectively (p = 0.002). The mean CRP 48-60 h post
      operatively was highly correlated with the CRP area under the curve, R = 0.88 (p
      < 0.001). A cut-off level of 15 mg/dl for CRP, 48- 60 h post-operatively, was
      calculated for patients with complications (sensitivity 93%, specificity 65%, p =
      0.003). CRP, fibrinogen and ESR were not related to fracture or type of
      operation, cognition, anesthetic risk, 1-month post-operative functioning and 6
      month mortality. CONCLUSIONS: CRP measurement in elderly patients operated for
      hip fracture may be valuable in assessing and monitoring complications.

PMID- 15258427
TI  - Relationship between somatotype and blood pressure in a group of
      institutionalized Venezuelan elders.
AB  - BACKGROUND: Somatotype, as an indirect measure of estimating body composition,
      provides an easy and comprehensive picture of body shape. Multiple investigations
      have shown the existence of an association between somatotype components and
      cardiovascular disease. OBJECTIVE: The aim of the present study was to examine
      the association of somatotype with blood pressure during ageing. METHODS: The
      Heath-Carter anthropometric somatotype and both systolic (SBP) and diastolic
      (DBP) blood pressures were recorded. The sample included 809 healthy
      institutionalized elders (370 males and 439 females) from geriatric units in
      Caracas, Venezuela. Ages ranged from 60 to 102 years. Product-moment correlation
      coefficients between somatotype components and both blood pressure readings were
      calculated. Principal component analysis and homogeneity analysis by means of
      alternative least squares tests were also performed. RESULTS: Females were more
      endomorphic and mesomorphic than males. Males were more ectomorphic than females.
      SBP showed a downward tendency with age in males, while in females the tendency
      was for the SBP to increase. Correlations among variables were from low to
      moderate and ranged from -0.37 to +0.34 in males, and from -0.18 to +0.32 in
      females. Correlations tended to be stronger in the younger age group and
      differences between sexes were found. A negative tendency in the correlation
      between ectomorphy and both SBP and DBP was found, except for the oldest age
      group, for which the correlation was positive. Endomorphy and mesomorphy showed a
      stable correlation pattern with blood pressure in males, while in females this
      pattern was more irregular and less consistent. CONCLUSION: Individuals with high
      levels of SBP and DBP had mean somatotypes, which were similar to those of other
      male groups characterized by myocardial infarct, coronary heart disease and the
      risk of hypertension, indicating that these somatotypes may be associated with
      cardiovascular risk factors. In particular, our results indicate that individuals
      who present a cardiovascular risk profile are more endomorphic and mesomorphic
      and less ectomorphic than those with a lower cardiovascular risk profile.

PMID- 15258428
TI  - Association of pulmonary function with cognitive performance in early, middle and
      late adulthood.
AB  - BACKGROUND: Pulmonary function has been associated with some measures of
      cognitive performance, mostly in late adulthood. This study investigated whether
      this association is present for a range of cognitive measures, at three stages of
      adulthood, and whether it remains after controlling for demographic, health and
      lifestyle factors. METHOD: The relationship between forced expiratory volume at 1
      s (FEV1), a measure of pulmonary function, and cognitive test performance was
      examined in three cohorts aged 20-24, 40-44 and 60-64. RESULTS: After controlling
      for demographic variables, smoking, physical activity, and respiratory disease,
      significant associations between FEV1 and cognitive test performance were evident
      in each age group for most cognitive measures. The association between FEV1 and
      measures of speed increased with age. CONCLUSION: FEV1 has a small but reliable
      positive association with cognitive test performance throughout adulthood,
      possibly reflecting a common physiological factor.

PMID- 15258429
TI  - CT diagnosis and outcome of primary brain tumours in the elderly: a cohort study.
AB  - BACKGROUND: The incidence of primary brain tumours (PBT) increases with age.
      Survival outcome depends on the treatment modality and histological type of the
      tumour. OBJECTIVES: To compare the survival outcome between those who had brain
      biopsy and those who did not among those who had PBT diagnosed by computerised
      tomography (CT). METHODS: We analysed data from 82 elderly patients who were
      admitted to a UK centre with close links to a neurosurgical unit. RESULTS: Age
      range was 62-99 years (median 74 years); 49 males and 33 females. 44 cases (54%)
      had brain biopsies of which 2 (5%) were not PBT. Both cases were malignant
      conditions, 1 case of metastasis and 1 leiomyosarcoma. Of 42 PBT, 34 (77%) were
      malignant gliomas. The remaining 8 cases were 4 astrocytomas, 2 meningiomas, 1
      cerebellar tumour and 1 cerebral lymphoma. Initial clinical misdiagnosis of
      cerebrovascular disease (CVA) or transient ischaemic attack (TIA) was very
      common, 70% in our cohort. Those who had brain biopsy were younger (median age
      72, range 62-81) compared to those who did not have brain biopsy (median age 77,
      range 65-91). A survival analysis for those who died comparing biopsy-proven
      malignant tumours (combined gliomas and astrocytomas (n = 37)) and those who did
      not have a biopsy (n = 37) showed that the latter had a shorter median time to
      receive definitive treatment after diagnosis, 8.0 days (95% CI; 5.4, 8.6) (n =
      20) compared to 40.0 days (95% CI; 32.5, 47.5) (n = 26) but shorter median length
      of survival, 47.0 days (95% CI; 32.3, 61.7) compared to 81.0 days (95% CI; 66.7,
      95.3) for those who had brain biopsy. Subgroup analysis of malignant gliomas
      between patients aged < or =70 years and those >70 years showed no significant
      difference in median length of survival, 74.0 days (95% CI; 54.0, 94.0) vs. 85.0
      days (95% CI; 59.0, 111.0), respectively. CONCLUSIONS: Our findings suggest that
      the older elderly are less likely to have aggressive therapy, and more likely to
      be diagnosed initially as cerebrovascular event (CVA/TIA). However, when they
      were given similar definitive treatment, their survival is comparable with their
      younger counterparts and therefore, age alone should not contraindicate radical
      treatment. Elderly patients should be selected for radical treatment on existing
      criteria, but age itself should not preclude radical treatment where it is
      otherwise appropriate to offer it.

PMID- 15258430
TI  - Do white matter changes have clinical significance in Alzheimer's disease?
AB  - BACKGROUND: Although white matter changes visible with MRI are generally
      considered to result from ischemia, it has become clear that these changes also
      appear in patients with Alzheimer's disease (AD). However, their significance in
      AD is unknown. OBJECTIVE: We evaluated the clinical significance of white matter
      changes in AD. METHODS: Ninety-six AD patients (79.4 +/- 5.92 years old) and 48
      age-matched control subjects (80.0 +/- 7.03 years old) participated in the study.
      Three neuroradiologists assessed the degree of periventricular hyperintensities
      (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas'
      rating scale. We examined whether there was a difference in the severity and the
      histogram pattern of the white matter changes, or in vascular factors
      (hypertension, diabetes mellitus, and ischemic heart disease) between the two
      groups. We also analyzed the association between the severity of the white matter
      changes and the degree of dementia (MMSE score and disease duration). RESULTS:
      There were no differences in the vascular factors between AD and control
      subjects. The degree of PVH in AD was severe compared with that in the control
      subjects. In histograms of the number of subjects with each degree of PVH
      severity, the distribution of AD patients had peaks at both the low and
      intermediate degrees of PVH, while most of the controls had a low degree of PVH.
      There was no difference in the degree or the histogram pattern of DWMH between
      the two groups. The severity of white matter changes was not associated with
      severity of dementia in AD. CONCLUSIONS: Although PVH might have several
      causative factors, and may have some clinical significance, the change itself
      does not contribute to the progression of AD.

PMID- 15258431
TI  - Living will, resuscitation preferences, and attitudes towards life in an aged
      population.
AB  - BACKGROUND: The growth of life-sustaining medical technology and greater
      attention to medical care at the end of life have provoked interest in issues
      related to advance care planning. OBJECTIVE: To investigate how having a living
      will (LW), resuscitation preferences, health condition, and life attitudes are
      related in home-dwelling elderly people. METHODS: In a cross-sectional
      descriptive study, detailed assessments were made of 378 home-dwelling elderly
      individuals participating in a cardiovascular prevention study (DEBATE Study).
      The participants were inquired about a preexistence of a written document (LW)
      concerning life-sustaining care, preferences of cardiopulmonary resuscitation
      (CPR) in their current situation, and attitudes towards life. General health,
      physical and cognitive functioning, the presence of depression, and quality of
      life were also assessed. RESULTS: Forty-four of the 378 participants (12%) had a
      LW. As compared with those without one (n = 334), there were more women [82%
      (36/44) vs. 63% (210/334)] and widows [57% (25/44) vs. 41% (135/334)] among those
      with a LW. They were also more educated and considered their health to be better.
      Despite having a LW, 46% (20/44) of them preferred CPR in their current
      condition, a proportion not statistically different from the 58% (194/334) of the
      individuals without a LW. In the whole sample, 39% (149/378) of the individuals
      preferred to forgo CPR. As compared with those preferring CPR, they were older,
      more often women, and widowed. Participants preferring to forgo CPR had a poorer
      quality of life, were more lonely, and showed signs of depression more often than
      those preferring CPR. The preference to forgo CPR was related to attitudes
      towards life regardless of physical or cognitive functioning. CONCLUSIONS: Having
      a LW does not reduce the reported preference of CPR which is related more to
      current mental status and life attitudes. In-depth assessment of the patient's
      preferences should be performed in any comprehensive care plan.

PMID- 15258432
TI  - Within-person variability as a dynamic measure of late-life development: new
      methodologies and future directions.
AB  - BACKGROUND: Intra-individual variability is becoming a focus of research in
      behavioural gerontology due to theoretical and methodological advances.
      OBJECTIVE: New directions in the study of intra-individual variability are
      described and unanswered questions are proposed. METHODS: Papers from the special
      issue of Gerontology on Intra-individual Change are reviewed. RESULTS: Key
      findings and approaches from this set of papers are identified, including types
      of latent growth curve models that incorporate dynamic elements and applications
      to the study of late-life cognition and affect. Theoretical issues that remain
      unresolved are outlined. CONCLUSION: Dynamic approaches to the measurement of
      change provide novel methods to answer new questions and evaluate existing
      theories. The focus on intra-individual variability adds a valuable dimension to
      gerontological research that may refine the way we describe behaviour and measure
      change.

PMID- 15258433
TI  - A case of emphysematous cystitis.

PMID- 15258434
TI  - The diagnosis of dementia is unspecified--report of a pilot survey of dementia in
      belgrade.

PMID- 15258435
TI  - The implications of different approaches to evaluating intervention: evidence
      from the study of language delay/disorder.
AB  - There is a pressure to both identify and expand the evidence base with regard to
      the treatment of speech and language disorders in children, as there is in other
      areas of speech and language therapy. This paper addresses two sources of
      evidence, a systematic review and meta-analysis of early language interventions
      and the monitoring of an early language target for socially disadvantaged
      children in Sure Start programmes in England. There is a growing number of
      efficacy studies in the field of speech and language disorders in children. For
      example, in a recent review for the Cochrane Collaboration in the UK 36 articles
      reporting a total of 33 different trials. Twenty-five of these articles provided
      sufficient information for use in a series of meta-analyses. The results indicate
      that speech and language therapy may be effective for children with phonological
      or expressive vocabulary difficulties. There is mixed evidence concerning the
      effectiveness of intervention for children with expressive syntax difficulties
      and little evidence available considering the effectiveness of intervention for
      children with receptive language difficulties. No significant differences were
      found between interventions administered by trained parents and clinicians. A
      number of gaps in the evidence base are identified. But such reviews are
      essentially retrospective and, while the results may be interesting for
      practitioners, they do not provide the whole picture. The paper then turns to a
      very different data set and the role of population monitoring, an approach to
      assessing the value of interventions which has not hitherto been used in any area
      of speech and language therapy. The data are derived from a year-on-year
      monitoring of the language output of 2-year-olds in Sure Start programmes in
      England. This is a programme funded by central government in the UK to reduce the
      impact of social disadvantage on children, parents and their communities. The
      practice and policy implications of these two different sources of information
      are considered. Who is the consumer of such information and what can they do with
      it once they have it?

PMID- 15258436
TI  - Occupational safety and health aspects of voice and speech professions.
AB  - A well-functioning voice is an essential tool for one third of the labour force.
      Vocal demands vary to a great extent between the different voice and speech
      professions. In professions with heavy vocal loading (e.g. school and
      kindergarten teachers), occupational voice disorders threatening working ability
      are common. Vocal loading is a combination of prolonged voice use and additional
      loading factors (e.g. background noise, acoustics, air quality) affecting the
      fundamental frequency, type and loudness of phonation or the vibratory
      characteristics of the vocal folds as well as the external frame of the larynx.
      The prevention and treatment of occupational voice disorders calls for improved
      occupational safety and health (OSH) arrangements for voice and speech
      professionals. On the basis of epidemiological and acoustic-physiological
      research, the presence of risk to vocal health can be substantiated. From the
      point of view of the physical load on the vocal apparatus, loading-related
      physiological changes (adaptation) may play a role in the occupational risk.
      Environmental factors affect vocal loading changes. In teaching professions, the
      working environment is shared with children, who benefit from amendments of OSH
      legislation concerning their teachers.

PMID- 15258437
TI  - 21st century literacy for a diverse world.
AB  - Literacy demands in the 21st century require that proficient readers do more than
      'read along the lines' or decode words and know their meaning. Proficient readers
      must be able to 'read between the lines', making relevant inferences to
      interpret, analyze, and synthesize information in texts; and 'read across the
      lines', applying these critical reading processes to multiple texts for purposes
      of problem-raising and problem-solving. This article will review literature on
      the cognitive and linguistic skills necessary for reading along the lines in a
      variety of scripts; the nature of the language and cognitive skills essential for
      the text comprehension necessary for reading between and across the lines, and
      the ways that culture and language influence text comprehension.

PMID- 15258438
TI  - A comparison of alcohol abusers who have and have not experienced blackouts.
AB  - This study examined the proposition that the experience of alcoholic blackouts is
      related to other indices of cerebral involvement in the alcoholic process. In
      particular it was suggested that those who experience alcoholic blackouts would
      also show signs of the effects of alcoholic damage in the form of lower scores on
      cognitive functions vulnerable to the effects of long-term alcohol abuse. While
      some evidence was found linking the experience of blackout to the severity of the
      alcohol problem, no relationship was found between cognitive functioning and the
      experience of blackout. The possibility that different mechanisms may underlie
      the various cognitive sequelae of alcohol abuse is raised.

PMID- 15258439
TI  - Interrater reliability of the structured interview for DSM-IV personality in an
      opioid-dependent patient sample.
AB  - We examined the interrater reliability of the Structured Interview for DSM-IV
      Personality (SIDP-IV) in an opioid-dependent patient sample at the criterion as
      well as at the diagnostic level for both categorical and dimensional data. At the
      criterion level (Cohen's kappa ranging from 0.76 to 0.93 and intraclass
      correlation coefficient ranging from 0.67 to 0.97) as well as at the diagnostic
      level (Cohen's kappa ranging from 0.66 to 1.00 and intraclass correlation
      coefficient ranging from 0.88 to 0.99), the reliability was excellent. The
      results suggest the SIDP-IV to be an adequate instrument for the assessment of
      personality disorders in opioid-dependent patients.

PMID- 15258440
TI  - Buprenorphine maintenance: office-based treatment with addiction clinic support.
AB  - INTRODUCTION: Buprenorphine has already been registered in 27 European countries
      for maintenance therapy in opioid-dependent patients. In our office-based
      prescription study we applied sublingual buprenorphine, initiating the treatment
      at the addiction clinic with subsequent treatment at the offices of general
      practitioners (GPs) to evaluate its efficacy and feasibility in two different
      treatment settings. METHODS: Sixty opioid-dependent patients were studied for a
      period of 15 weeks. The first 3 weeks of treatment initiation took place at the
      addiction clinic, followed by 12 weeks of treatment by GPs. Mean outcome measures
      were retention rate and additional consumption of illicit substances in addition
      to the evaluation of whether buprenorphine can be prescribed successfully by GPs.
      RESULTS: The retention rate was 57% (n = 34). No significant differences occurred
      between the treatment phases at the specialized addiction unit and the GPs'
      offices. During the 15-week period a significant improvement in well-being and a
      significant reduction in craving for heroin (p < 0.001) and cocaine (p < 0.001)
      could be calculated for patients stabilized on a mean dose of 16 mg
      buprenorphine. Furthermore a significant reduction in additional consumption of
      opioids (p < 0.001) was found. DISCUSSION: Our results show the involvement of
      office-based prescription, which should further encourage colleagues to treat
      opioid-dependent subjects with buprenorphine to make more treatment options for
      this target group available.

PMID- 15258441
TI  - Medical assessment in drug addicts: reliability and validity of the Cumulative
      Illness Rating Scale (Substance Abuse version).
AB  - OBJECTIVE: To adapt the Cumulative Illness Rating Scale for its use in substance
      abuse patients (CIRS-SA) and to assess the reliability, internal consistency, and
      validity of the instrument. METHOD: One-hundred outpatients of both sexes, 62 men
      and 38 women, with a mean (SD) age of 32.4 (7.9) years (range 19-57), all of them
      fulfilling the DSM-IV criteria for any substance abuse disorder. Internal
      consistency was calculated with Cronbach's alpha coefficient. Test-retest and
      interrater reliability was assessed with the intraclass correlation coefficient
      and Wilcoxon z. Validity of the scale was assessed with Kendall's tau correlation
      coefficient. RESULTS: The final CIRS-SA version had a total of 13 items.
      Cronbach's alpha coefficient was 0.57. All intraclass correlation coefficients
      were above 0.7, and some items showed exact coincidence. The stability of the
      CIRS-SA scale in a 1-month test re-test reassessment was demonstrated. The CIRS
      SA score showed a significant correlation with all consultant scores. CONCLUSION:
      CIRS-SA is a reliable and valid instrument to assess and to determine
      systematically the physical condition of substance abusers in whom infections,
      particularly by the HIV, are highly prevalent.

PMID- 15258442
TI  - Progression of a general substance use pattern among adolescents in Switzerland?
      Investigating the relationship between alcohol, tobacco, and cannabis use over a
      12-year period.
AB  - Many studies have shown that different risk or problem behaviors in adolescence
      are interrelated. Given the increased use of various substances among adolescents
      in the United States and in most European countries, the question emerges whether
      there are more substance use "specialists" or a progression of a general
      substance use pattern. If the latter is the case, the interrelatedness of the
      different substances should remain stable over time in a representative sample
      and among subgroups characterized by gender and language. Data from 4,146 15-year
      olds in Switzerland surveyed in 1986, 1994 and 1998 were analyzed, using
      confirmatory factor analyses based on polychoric correlations. Smoking,
      drunkenness and cannabis use greatly increased over the 12-year period. However,
      in the different survey years, the factor structure did not differ for all 15
      year-olds in general or for subgroups. This progression of a general pattern
      refers to an increased normalization of recreational substance use in general,
      not only of cannabis use. Favorable attitudes towards general substance use are a
      challenge to substance use prevention in adolescence, and reveal a need for more
      research on such a progression in other countries.

PMID- 15258443
TI  - Stability of successful long-term adjustment in alcohol dependence: a follow-up
      study 15 years after the first long-term follow-up.
AB  - From a large consecutive sample (n = 1,312) of hospital-treated alcoholics with
      multiaxial ratings, 105 were chosen for personal examination two decades after
      the subjects' first admission (1949-1969) for alcohol problems. To study patterns
      of successful adjustment, 70 were chosen on the basis of a good social adjustment
      (health insurance data) at follow-up, whereas the control subjects had been
      granted a disability pension. The first follow-up was carried through in 1982
      1983. In 1998-1999, the same 105 subjects were studied concerning mortality rate
      and adjustment patterns. In the good social adjustment group, 33% had deceased as
      compared with 63% in the control group (p < 0.01). Twenty-three out of 44
      surviving subjects accepted a personal interview. Favourable adjustment was
      generally reported as being stable over the follow-up period. Several subjects
      reported stable non-problem drinking and others a change between abstinent and
      non-abstinent adjustment patterns.

PMID- 15258444
TI  - Readiness to change in a clinical sample of problem drinkers: relation to alcohol
      use, self-efficacy, and treatment outcome.
AB  - According to the transtheoretical model of behaviour change, individuals addicted
      to psychotropic drugs typically cycle through a sequence of five discrete stages
      (precontemplation, contemplation, preparation, action, and maintenance) before
      achieving sustained long-term abstinence and moderation, respectively. A number
      of English-language questionnaires have been developed to assess client
      motivation in accordance with the stages of change approach. The present study
      aimed to expand the research on the transtheoretical model by establishing the
      factor structure of a German-language version of the Stages of Change Readiness
      and Treatment Eagerness Scale (SOCRATES) in a large sample of alcohol-dependent
      inpatients (n = 350). Furthermore, the relation of client motivation to alcohol
      use, self-efficacy and treatment outcome at 3-month follow-up was examined.
      Exploratory factor analysis revealed three separate dimensions of readiness to
      change (Taking Steps, Recognition, and Ambivalence). The factorial structure of
      the German-language SOCRATES corresponded almost exactly to that of the original
      version. Readiness to change accounted for 9.4% of the variance in treatment
      outcome. Moreover, readiness to change was positively related to pretreatment
      self-efficacy.

PMID- 15258445
TI  - Treatment of early diagnosed HCV infection in hemodialyzed patients with
      interferon-alpha. Treatment of hepatitis C.
AB  - BACKGROUND: Acute and early diagnosed hepatitis C virus (HCV) infections are rare
      diagnoses. Patients on regular dialysis treatment (RDT) are at risk of acquiring
      HCV infection. AIMS OF THE STUDY: (1) To determine the efficacy and safety of two
      phase induction treatment of acute and early diagnosed HCV infections in patients
      on RDT, and (2) to establish the importance of serum HCV RNA testing at defined
      time points of treatment for the prediction of the therapeutic effect.
      THERAPEUTIC PROTOCOL: Antiviral treatment consisted of two different phases:
      phase A therapy was interferon (IFN)-alpha 2b 10 million units (MU) s.c.
      administered daily for 21 days followed by phase B with IFN-alpha 2b 3 MU s.c.
      administered 3 times weekly for 12 weeks. RESULTS: (1) Efficacy of the treatment:
      A sustained virological response (SVR) was achieved in a total of 13/18 patients
      (72%). SAFETY: We did not observe any serious side effects of the treatment. The
      most pronounced side effect was the myelosuppression caused by IFN-alpha. (2) SVR
      prediction: Patients with negative serum HCV RNA at day 6 achieve SVR more
      frequently than those with positive HCV RNA at day 6 (p = 0.074). CONCLUSIONS:
      Treatment of acute and early diagnosed HCV infections in hemodialyzed patients is
      much more effective than treatment of chronic infection. Even relatively high
      doses of IFN at the beginning of therapy (10 MU daily) are tolerated well by the
      patients.

PMID- 15258446
TI  - New advances on the functions of epidermal growth factor receptor and ceramides
      in skin cell differentiation, disorders and cancers.
AB  - Recent advances in understanding of the biological functions of the epidermal
      growth factor and epidermal growth factor receptor (EGF-EGFR) system and ceramide
      production for the maintenance of skin integrity and barrier function are
      reported. In particular, the opposite roles of EGFR and ceramide cascades in
      epithelial keratinocyte proliferation, migration and terminal differentiation are
      described. Moreover, the functions of ceramides in the epidermal permeability
      barrier are reviewed. The alterations in EGFR signaling and ceramide metabolism,
      which might be involved in the etiopathogenesis of diverse skin disorders and
      cancers, are described. New progress in understanding of skin organization, which
      might provide the basis for the design of new transcutaneous drug delivery
      techniques as well as for the development of new therapies of skin disorders and
      cancers, are reported.

PMID- 15258447
TI  - Using skin models to assess the effects of a protection cream on skin barrier
      function.
AB  - BACKGROUND: There is a basic necessity to understand the mechanisms of the
      protective effects of emulsions. This would promote the development of protective
      cosmetics and therefore improve the prevention and treatment of occupational skin
      diseases. However, for such studies, no reliable skin model is available.
      OBJECTIVE: An in vitro skin model test was developed to evaluate the protective
      mechanism of cosmetic ingredients. METHODS: The efficacy of three products was
      assessed by an in vivo test (Repetitive Occlusive Irritation Test) and then 3
      dimensional skin model tests were carried out. RESULTS: In vivo test results
      demonstrate that the best protection against sodium dodecyl sulphate is offered
      by a multiple emulsion. In the case of a skin model test, sodium dodecyl sulphate
      led to cell damage, an increase in pro-inflammatory markers and some barrier
      lipids. The multiple emulsion increased the content of skin lipids, without
      inducing irritation or cell death. CONCLUSION: Skin models react similarly to
      sodium dodecyl sulphate compared to human skin and therefore they are suitable to
      study barrier repair after sodium dodecyl sulphate damage. It is likely that the
      superior protective effect of the multiple emulsion in vivo is based on the
      increased amount of skin barrier lipids.

PMID- 15258448
TI  - Characterization of transport of chlorhexidine-loaded nanocapsules through
      hairless and wistar rat skin.
AB  - Nanocapsules appear a promising approach as a drug system for topical
      application. However, the transport mechanism of nanocapsule-associated drug
      through the skin is still being questioned. In the present study, the transport
      of chlorhexidine-loaded poly(epsilon-caprolactone) nanocapsules through full
      thickness and stripped hairless rat skin was investigated in static-diffusion
      cell. The chlorhexidine permeation profiles fitting the Fickian diffusion model
      showed that the drug encapsulation reduced the percutaneous drug absorption
      through stripped skin. Possible nanocapsule transport within skin conducts was
      suggested from the analysis of permeation parameters and confirmed by confocal
      laser microscopy studies. Furthermore, the chlorhexidine permeation and drug
      release data were highly correlated, suggesting that the magnitude of
      percutaneous absorption was controlled by the diffusion across the polymeric
      carrier. The behavior of nanocapsules at the skin interface was investigated by
      contact angle and surface tension measurements. The small 'wetting' of the
      nanocapsule on the stratum corneum surface preserved the mechanical integrity of
      the carrier characterized by a high specific surface at the skin interface. The
      flexibility of the nanocapsules assured a satisfying bioadhesion to the skin,
      whereas the rigidity of the carrier limited the molecular 'spill' into the skin
      and controlled the drug delivery to the skin.

PMID- 15258449
TI  - The use of ozone as an oxidizing agent to evaluate antioxidant activities of
      natural substrates.
AB  - Ozone, the main component of photochemical smog and air pollution, can damage the
      skin by oxidizing stratum corneum enzymes, lipids and structural proteins. We
      have developed a rapid screening assay to determine free radical scavenging
      capacity of various active ingredients that are frequently used in personal care
      products. Several known antioxidants including vitamin C, vitamin E analog
      Trolox, walnut seed extract, lipoic acid and ergothioneine inner salt were
      assayed for their ability to neutralize ozone-induced oxidation of beta
      phycoerythrin, a fluorescent reporter protein derived from algae. The free
      radical scavenging capacities of these antioxidants were quantified and compared.
      The results demonstrate that this assay is a valuable primary screening tool for
      identifying antioxidant activity of natural or synthetic substrates that can be
      used in personal care products to protect the uppermost layer of our skin from
      oxidizing damage induced by O3.

PMID- 15258450
TI  - Percutaneous penetration of topically applied melatonin in a cream and an
      alcoholic solution.
AB  - In a clinical study, the skin penetration properties of melatonin 0.01% in a
      cream and 0.01 and 0.03% in a solution were investigated by evaluation of the
      serum melatonin levels over a 24-hour time course in 15 healthy volunteers. Blood
      samples for melatonin measurements were taken at 9.00 a.m. before applying the
      test preparations and 1, 4, 8 and 24 h after application. The measurements were
      carried out by radioimmunoassay for melatonin. In 15 volunteers, the serum levels
      of melatonin before application of the topical preparations were between 0.6 and
      15.9 pg/ml. After application of the 0.01% melatonin cream, there was a steady
      increase starting from 9.00 a.m. up to a mean serum value of 9.0 pg/ml at 9.00
      a.m. the next day. The solution of 0.01% melatonin also showed an increase,
      starting from 5.00 p.m., up to a mean melatonin level of 12.7 pg/ml 24 h after
      application. The solution containing 0.03% melatonin resulted in elevated
      melatonin levels 1 and 8 h after application. The values were 18.1 and 19.0
      pg/ml. The cumulative melatonin values for each preparation were 7.1, 8.6 and
      15.7 pg/ml, respectively. This study shows that the strongly lipophilic substance
      melatonin is able to penetrate through the skin and leads to dose- and galenic
      dependent melatonin levels in the blood. No increase of melatonin above the
      physiological range was observed.

PMID- 15258451
TI  - Haloperidol attenuates beta-amyloid-induced calcium imbalance in human
      fibroblasts.
AB  - BACKGROUND: Antipsychotics are widely used in the treatment of behavioral and
      psychological symptoms of dementia. A low frequency of Alzheimer's disease in
      patients with schizophrenia is reported, and it has been proposed that
      antipsychotic medications, such as haloperidol, may be responsible. Disruption of
      intracellular calcium levels is considered to play a key role in beta-amyloid
      induced neurotoxicity in Alzheimer's disease. Haloperidol has also been reported
      to interact with calcium homeostasis through dopamine-2 and sigma-1 receptors,
      and other, yet unknown mechanisms. OBJECTIVE: Therefore, we investigated whether
      differences in the basal intracellular free calcium levels of cultured cutaneous
      fibroblasts--cells that do not express dopamine-2 and sigma-1 receptors--derived
      from sporadic Alzheimer patients and from age-matched control individuals after
      haloperidol treatment might be present. METHODS: Intracellular calcium level was
      measured in Fura-2AM-loaded human fibroblasts by dual wavelength
      spectrofluorimetry. RESULTS: Alzheimer cells exhibited significantly lower
      calcium level as compared to the control cultures. Exposure of fibroblasts to
      beta-amyloid peptide resulted in increased calcium concentration of the control
      cells, but not of Alzheimer fibroblasts. Co-incubation of cultures with a
      therapeutic dose of haloperidol blocked the beta-amyloid-induced elevation of
      calcium. CONCLUSION: This finding indicates that haloperidol efficiently
      countervails ionic imbalance and suggests that it may serve as a potential agent
      in alleviating neurotoxic effects of beta-amyloid peptide.

PMID- 15258452
TI  - Topical activity of ascorbic acid: from in vitro optimization to in vivo
      efficacy.
AB  - We present here a new cosmetic formula system containing 3% ascorbic acid based
      on an optimized oil-in-water (O/W) emulsion. This formulation demonstrated a good
      long-term stability of the active ingredient and also of the emulsion itself. It
      could be deduced from in vitro release studies that this O/W emulsion enabled a
      better release of the hydrophilic active agent than an alternative W/O emulsion.
      By measuring the ultraweak photon emission, which is a well-established parameter
      for the oxidative stress in the skin, the high in vivo antioxidant capacity of 3%
      ascorbic acid was demonstrated after 1 week of product application. This placebo
      controlled study also proved that ascorbic acid in an O/W cream reduced oxidative
      stress in human skin significantly better than the derivative sodium ascorbyl-2
      phosphate, a more stable vitamin C replacement commonly used in cosmetic
      formulations. With increasing age, the number of papillae in the epidermal-dermal
      junction zone in human skin are reduced. This implies a possible consequence of
      reduced mechanical resistance of the skin and impaired supply of the epidermis
      with nutrients. In a 1-month placebo-controlled study on 25 human volunteers, a
      significant increase in the number of dermal papillae after application of the 3%
      ascorbic acid cream was demonstrated, using a confocal laser scanning microscope.
      Fine lines and wrinkles are a characteristic sign of aged and especially photo
      aged skin. Application of 3% ascorbic acid in a 12-week placebo-controlled usage
      study indicated a significant reduction of facial wrinkles. Altogether, 3%
      ascorbic acid in a cosmetic O/W emulsion has been shown to be appropriately
      stable and to enable a good release of the active agent in vitro as a
      precondition for a high efficacy in vivo. Application in vivo resulted in a
      significant reduction of oxidative stress in the skin, an improvement of the
      epidermal-dermal microstructure and a reduction of fine lines and wrinkles in
      aged skin. These results were received within a relatively short period of time
      of product application.

PMID- 15258455
TI  - Stop place coding: an acoustic study of CV, VC#, and C#V sequences.
AB  - This study investigated stop + vowel coarticulation as a coding mechanism for
      differentiation of stop place categories in an F2-defined stimulus space. Locus
      equations (LEs) were used to index the extent of coarticulation in three
      contexts: (1) onset stop + vowel utterances [.CV]; (2) within-syllable vowel +
      coda stop utterances [VC#], and (3) across-syllable/word coda stop + vowel
      utterances [C#V]. Five speakers of American English and 2 speakers of Persian
      produced [CV1.CV2] (English and Persian), [tV1C#V2t] (English) and [dV1C#V2t]
      (Persian) tokens with voiced labial, alveolar/dental, and velar stops surrounded
      by a variety of vowels. In the across-syllable/word boundary condition [C#V2] the
      extent of anticipatory coarticulation was much reduced relative to traditionally
      measured onset [CV2] syllables. LE slopes derived across the syllable/word
      boundary, however, still differed between stop places in the same order as onset
      CVs. LE slopes derived from within-syllable [V1C#] sequences, however, did not
      differ between stop places.

PMID- 15258456
TI  - On the back of the tongue: dorsal sounds in Australian languages.
AB  - In this paper we provide an overview of dorsovelar articulations and acoustics in
      several Australian Aboriginal languages, and we compare these results with data
      from English. We examine languages that have a single dorsal, as well as
      languages that have two dorsal places of articulation. Using direct palatography
      and F2 transition measures, we show that Australian languages appear to have a
      distinct velar target for each of the three major vowel contexts, with a high
      degree of coarticulation between each velar allophone and its following vowel
      target, whilst English has only two velar targets--back and non-back, with a
      lower degree of coarticulation between velar allophones and their corresponding
      vowel targets. Thus, whilst the range of allophonic variation for velars extends
      further back in the Australian Aboriginal languages than in English, there
      appears to be no difference in the articulation of velars in the front vowel
      context. Drawing on results from the biomechanics, language acquisition, speech
      perception and acoustics literatures, we suggest that this result may be due to
      conflict between systemic constraints imposed by the place-rich consonant systems
      of Aboriginal languages and universal acoustic constraints on the identity of
      front-velar sounds, which may contribute to the instability of such articulations
      and the relative infrequency of velar + high vowel combinations in the world's
      languages.

PMID- 15258457
TI  - Programmed cell death in the development of the vertebrate inner ear.
AB  - Programmed cell death is known to be an essential process for accurate ontogeny
      during the normal development of the inner ear. The inner ear is a complex
      sensory organ responsible for equilibrium and sound detection in vertebrates. In
      all vertebrates, the inner ear develops from a single ectodermic patch on the
      surface of the embryo's head, which undergoes a series of morphological changes
      to give rise to the complex structure of the adult inner ear. Enlargement and
      morphogenesis of the inner ear primordium is likely to depend on cellular
      division, growth, migration, differentiation and apoptosis. Here we describe the
      regions of programmed cell death that contribute to the final morphological
      aspect of the adult inner ear. The few studies that focus on the molecules that
      control this process during inner ear development indicate that the molecules and
      intracellular signaling pathways activated during the apoptotic response in the
      inner ear are similar to the previously described for the nervous system. In this
      review, we will describe some of the growth factors and key pathways that
      regulate pro- and anti-apoptotic signals and how they cross talk to determine the
      apoptotic or survival fate of cells in the development of the inner ear.

PMID- 15258458
TI  - Chondroptosis: a variant of apoptotic cell death in chondrocytes?
AB  - Evidence has accumulated in recent years that programmed cell death (PCD) is not
      necessarily synonymous with the classical apoptosis, as defined by Kerr and
      Wyllie, but that cells use a variety of pathways to undergo cell death, which are
      reflected by different morphologies. Although chondrocytes with the hallmark
      features of classical apoptosis have been demonstrated in culture, such cells are
      extremely rare in vivo. The present review focuses on the morphological
      differences between dying chondrocytes and classical apoptotic cells. We propose
      the term 'chondroptosis' to reflect the fact that such cells are undergoing
      apoptosis in a non-classical manner that appears to be typical of programmed
      chondrocyte death in vivo. Unlike classical apoptosis, chondroptosis involves an
      initial increase in the endoplasmic reticulum and Golgi apparatus, reflecting an
      increase in protein synthesis. The increased ER membranes also segment the
      cytoplasm and provide compartments within which cytoplasm and organelles are
      digested. In addition, destruction occurs within autophagic vacuoles and cell
      remnants are blebbed into the lacunae. Together these processes lead to complete
      self-destruction of the chondrocyte as evidenced by the presence of empty
      lacunae. It is speculated that the endoplasmic reticulum pathway of apoptosis
      plays a greater role in chondroptosis than receptor-mediated or mitochondrial
      pathways and that lysosomal proteases are at least as important as caspases.
      Because chondroptosis does not depend on phagocytosis, it may be more
      advantageous in vivo, where chondrocytes are isolated within their lacunae. At
      present the initiation factors or the molecular pathways involved in
      chondroptosis remain unclear.

PMID- 15258459
TI  - Id-1 expression and cell survival.
AB  - The Id (inhibitor of differentiation or DNA binding) helix-loop-helix (HLH)
      proteins are a group of dominant negative regulators of basic HLH transcriptional
      factors which promote cell differentiation. Recent evidence has revealed that Id
      proteins, especially Id-1, are also able to promote cell proliferation and cell
      cycle progression through inactivation of tumour suppressor and activation of
      growth promoting pathways in mammalian cells. In addition, upregulation of Id-1
      has been found in many types of human cancer and its expression levels are also
      associated with advanced tumour stage. Furthermore, ectopic expression of Id-1 in
      human cancer cells is able to induce cell proliferation under sub-optimal
      conditions and protect the cells against apoptosis. These lines of evidence
      strongly indicate Id-1 as a positive regulator of cell growth and its expression
      may be a key factor required for tumour cell proliferation. This review will
      discuss recent evidence on the role of Id-1 in cell proliferation and survival,
      and its significance in malignant transformation. In addition, we will highlight
      the recent development in the understanding of the molecular mechanisms
      responsible for the action of Id-1 in promoting cell survival and tumourigenesis.
      Finally, the therapeutic implications through inactivation of Id-1 in the
      treatment of human cancer will also be addressed.

PMID- 15258460
TI  - Immune modulation and apoptosis induction: two sides of the antitumoral activity
      of imiquimod.
AB  - Imiquimod, the first member of the imidazoquinoline family of immune response
      modifiers, has proven good clinical efficacy against basal cell carcinomas and
      actinic keratoses in several independent studies. In addition, there is recent
      evidence that imiquimod is also efficacious against other tumors such as
      cutaneous metastases of malignant melanoma or vascular tumors. Imiquimod exerts
      its antitumoral effect, at least in part, through binding to TLR-7 and TLR-8 on
      dendritic cells followed by secretion of a multitude of proinflammatory
      cytokines. The net result of this proinflammatory activity is a profound tumor
      directed cellular immune response. However, recent experimental and clinical data
      indicate that imiquimod also possesses considerable direct pro-apoptotic activity
      against tumor cells both in vitro and in vivo. This novel mode of action appears
      to be independent of membrane bound death receptors, but involves caspase
      activation. Induction of apoptosis by imiquimod is, at least in part, presumably
      mediated through Bcl-2-dependent release of mitochondrial cytochrome c and
      subsequent activation of caspase-9. The structural analogue, resiquimod,
      exhibited very limited, if any, such pro-apoptotic activity, possibly due to its
      lacking ability to enter the cell. Bypassing molecular mechanisms of apoptosis
      deficiency by a topical compound may be of great utility for treating certain
      cutaneous tumors.

PMID- 15258461
TI  - BAX Inhibitor-1, an ancient cell death suppressor in animals and plants with
      prokaryotic relatives.
AB  - BAX Inhibitor-1 (BI-1) was originally described as testis enhanced gene
      transcript in mammals. Functional screening in yeast for human proteins that can
      inhibit the cell death provoking function of BAX, a proapoptotic Bcl-2 family
      member, led to functional characterisation and renaming of BI-1. The
      identification of functional homologues of BI-1 in plants and yeast widened the
      understanding of BI-1 function as an ancient suppressor of programmed cell death.
      BI-1 is one of the few cell death suppressors conserved in animals and plants.
      Computer predictions and experimental data together suggest that BI-1 is a
      membrane spanning protein with 6 to 7 transmembrane domains and a cytoplasmic C
      terminus sticking in the endoplasmatic reticulum and nuclear envelope. Proteins
      similar to BI-1 are present in other eukaryotes, bacteria, and even viruses
      encode BI-1 like proteins. BI-1 is involved in development, response to biotic
      and abiotic stress and probably represents an indispensable cell protectant. BI-1
      appears to suppress cell death induced by mitochondrial dysfunction, reactive
      oxygen species or elevated cytosolic Ca(2+) levels. This review focuses on the
      present understanding about BI-1 and suggests potential directions for further
      analyses of this increasingly noticed protein.

PMID- 15258462
TI  - Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy.
AB  - Aberrantly expressed or mutated proteins in cancer cells evoke immune
      recognition, but host reactions are usually insufficient to prevent disease
      progression. Vaccination with irradiated tumor cells engineered to secrete
      granulocyte-macrophage colony stimulating factor (GM-CSF) augments host immunity
      through improved tumor antigen presentation by recruited dendritic cells and
      macrophages. By analyzing the immune response of a metastatic melanoma patient
      who achieved a long-term response to vaccination, we identified melanoma
      inhibitor of apoptosis protein (ML-IAP) as a target for immune-mediated tumor
      destruction. Vaccination stimulated a coordinated cellular and humoral reaction
      to ML-IAP that was associated with extensive tumor necrosis, whereas lethal
      disease progression was linked with the loss of ML-IAP expression and the absence
      of intra-tumoral lymphocyte infiltrates. These findings demonstrate that ML-IAP
      can serve as a tumor rejection antigen, although additional vaccine targets will
      be required to circumvent immune escape and tumor heterogeneity.

PMID- 15258463
TI  - The viral death effector Apoptin reveals tumor-specific processes.
AB  - Several natural proteins, including the cellular protein TRAIL and the viral
      proteins E4orf4 and Apoptin, have been found to exert a tumor-preferential
      apoptotic activity. These molecules are potential anti-cancer agents with direct
      clinical applications. Also very intriguing is their possible utility as sensors
      of the tumorigenic phenotype. Here, we focus on Apoptin, discussing recent
      research that has greatly increased our understanding of its tumor-specific
      processes. Apoptin, which kills tumor cells in a p53- and Bcl-2-independent,
      caspase-dependent manner, is biologically active as a highly stable, multimeric
      complex consisting of 30 to 40 monomers that form distinct superstructures upon
      binding cooperatively to DNA. In tumor cells, Apoptin is imported into the
      nucleus prior to the induction of apoptosis; this contrasts with the situation in
      primary or low-passage normal cell cultures where nuclear translocation of
      Apoptin is rare and inefficient. Apoptin contains two autonomous death-inducing
      domains, both of which exhibit a strong correlation between nuclear localization
      and killing activity. Nevertheless, forced nuclear localization of Apoptin in
      normal cells is insufficient to allow induction of apoptosis, indicating that
      another activation step particular to the tumor or transformed state is required.
      Indeed, a kinase activity present in cancer cells but negligible in normal cells
      was recently found to regulate the activity of Apoptin by phosphorylation.
      However, in normal cells, Apoptin can be activated by transient transforming
      signals conferred by ectopically expressed SV40 LT antigen, which rapidly induces
      Apoptin's phosphorylation, nuclear accumulation and the ability to induce
      apoptosis. The region on LT responsible for conferring this effect has been
      mapped to the N-terminal J domain. In normal cells that do not receive such
      signals, Apoptin becomes aggregated, epitope-shielded and is eventually degraded
      in the cytoplasm. Finally, Apoptin interacts with various partners of the human
      proteome including DEDAF, Nmi and Hippi, which may help to regulate either
      Apoptin's activation or execution processes. Taken together, these recent
      advances illustrate that elucidating the mechanism of Apoptin-induced apoptosis
      can lead to the discovery of novel tumor-specific pathways that may be
      exploitable as anti-cancer drug targets.

PMID- 15258465
TI  - Mitochondrial translocation of p53 and mitochondrial membrane potential (Delta
      Psi m) dissipation are early events in staurosporine-induced apoptosis of wild
      type and mutated p53 epithelial cells.
AB  - The mitochondrial localization of p53 is an important event in p53-dependent
      apoptosis. Some p53 mutants defective for transcription also facilitate apoptosis
      through changes of the mitochondria. Here, apoptosis of HeLa and CaSki cells
      (p53(wt)), C33A and HaCat cells (p53(mt)) and SaOs-2 cells (p53 deficient) was
      induced by 300 nM staurosporine. We showed that wild-type p53, as well as p53
      mutants, were transiently located to the mitochondria with changes in the
      mitochondrial membrane potential (Delta Psi m). However, in C33A cells harboring
      a p53 mutated on its DNA binding domain, Delta Psi m collapse and Sub-G1 DNA
      content were reduced compared to p53(wt) cells, whereas no significant difference
      was observed in HaCat cells with a p53 mutated on UV hot spots. In addition,
      inhibition of the mitochondrial permeability transition pores by cyclosporine A
      significantly reduced the Delta Psi m loss and the sub-G1 DNA content in p53
      positive cells. These results indicate that Delta Psi m collapse is an early and
      necessary event, which plays an important role in apoptosis of immortal mammalian
      cells.

PMID- 15258464
TI  - 2-MeOE2bisMATE induces caspase-dependent apoptosis in CAL51 breast cancer cells
      and overcomes resistance to TRAIL via cooperative activation of caspases.
AB  - 2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite which
      inhibits tubulin polymerisation and has anti-tumour and anti-angiogenic activity.
      2-MeOE2 induces apoptosis in a wide range of cancer cell types and has recently
      been demonstrated to cooperate with TRAIL to induce apoptosis in breast cancer
      cells. 2-Methoxyoestradiol-3,17-bis-O,O-sulphamate (2-MeOE2bisMATE) is a
      sulfamoylated derivative of 2-MeOE2 with enhanced activity and improved
      pharmacokinetic properties, and 2-MeOE2bisMATE is a promising candidate for early
      clinical trials. It is important, therefore, to understand the mechanisms by
      which 2-MeOE2bisMATE acts, and whether it retains the ability to cooperate with
      TRAIL. We demonstrate that 2-MeOE2bisMATE-induced apoptosis of CAL51 breast
      cancer cells was associated with rapid activation of caspase 3 and 9, but not
      caspase 8 (as measured by BID cleavage) and was completely prevented by the
      caspase inhibitor zVADfmk. Interfering with Fas- or TRAIL-receptor function did
      not prevent 2-MeOE2bisMATE-induced apoptosis. Whereas CAL51 cells were resistant
      to TRAIL-induced apoptosis, 2-MeOE2bisMATE and TRAIL cooperated to induce cell
      death. This apoptosis was associated with enhanced activation of caspases, but
      not increased expression of the DR5 TRAIL receptor, previously demonstrated to be
      induced by 2-MeOE2. Therefore, 2-MeOE2bisMATE-induced apoptosis is dependent on
      caspases and like 2-MeOE2, 2-MeOE2bisMATE can overcome resistance to TRAIL by
      stimulating activation of downstream caspases. Our results suggest that 2
      MeOE2bisMATE and TRAIL might be a particularly effective combination of anti
      cancer agents.

PMID- 15258466
TI  - Differentiation-induced HL-60 cell apoptosis: a mechanism independent of
      mitochondrial disruption?
AB  - HL-60 cell differentiation into neutrophil like cells is associated with their
      induction of apoptosis. We investigated the cellular events that occur pre and
      post mitochondrial permeability transition to determine the role of the
      mitochondria in the induction of differentiation induced apoptosis. Pro-apoptotic
      Bax was translocated to and cleaved at the mitochondrial membrane in addition to
      t-Bid activation. These processes contributed to mitochondrial membrane
      disruption and the release of cytochrome c and Smac/DIABLO. The release of
      cytochrome c was caspase independent, as the caspase inhibitor Z-VAD.fmk, which
      inhibited apoptosis, did not block the release of cytochrome c. In contrast, the
      release of Smac/DIABLO was partially inhibited by caspase inhibition indicating
      differential release pathways for these mitochondrial pro-apoptotic factors. In
      addition to caspase inhibition we assessed the effects of the Bcl-2 anti
      apoptotic family on differentiation induced apoptosis. BH4-Bcl-xl-TAT recombinant
      protein did not delay apoptosis, but did block the release of cytochrome c and
      Smac/DIABLO. Bcl-2 over-expression also inhibited differentiation induced
      apoptosis but was associated with the inhibition of the differentiation process.
      Differentiation mediated mitochondrial release of cytochrome c and Smac/DIABLO,
      may not trigger the induction of apoptosis, as BH4-Bclxl-TAT blocks the release
      of pro-apoptotic factors from the mitochondria, but does not prevent apoptosis.

PMID- 15258467
TI  - Intestinal ischemic preconditioning: less xanthine accumulation relates with less
      apoptosis.
AB  - Ischemic preconditioning has shown to reduce apoptosis in the intestinal mucosa
      during ischemia/reperfusion. This study evaluated if the decrease of apoptotic
      events found during preconditioning could be related with a reduction of the
      substrate (i.e., xanthine/hypoxanthine) available for xanthine oxidase (XO).
      Animals were randomly assigned to the following study groups: C, control; I/R,
      ischemia/reperfusion; P+I/R, ischemic preconditioning; P+I/R+H/X, ischemic
      preconditioning plus hypoxanthine/xanthine, and P+I/R+H/X+Allo, ischemic
      preconditioning plus hypoxanthine/xanthine plus allopurinol. Caspase-3 activity,
      DNA fragmentation and TUNEL staining increased in the I/R group compared to
      control. Ischemic preconditioning (P+I/R group) was able to reverse these
      apoptotic variables to a level similar to that of control rats. The addition of
      hypoxanthine/xanthine to rats subjected to ischemic preconditioning (P+I/R+H/X
      group) showed the highest apoptotic activity; however, further addition of
      allopurinol (P+I/R+H/X+Allo group) decreased significantly apoptotic activity and
      events. In conclusion, intestinal ischemic preconditioning is able to reduce
      apoptosis during the following sustained ischemia/reperfusion event because of a
      reduced accumulation of xanthine/hypoxanthine nucleotide.

PMID- 15258468
TI  - Degradation of GFP-labelled POM121, a non-invasive sensor of nuclear apoptosis,
      precedes clustering of nuclear pores and externalisation of phosphatidylserine.
AB  - The nuclear pore membrane protein POM121 is specifically degraded during
      apoptosis by a caspase-3-dependent process enabling early detection of apoptosis
      in living cells expressing POM121-GFP. Here we further investigated temporal
      aspects of apoptotic degradation of POM121-GFP. We demonstrate that decreased
      POM121-GFP fluorescence precedes annexin V-labelling of apoptotic cells. This
      indicates that degradation of the nuclear pore complex starts prior to
      redistribution of plasma membrane phosphatidylserine, which serves as a signal
      for phagocytotic elimination of apoptotic cells. Furthermore, a caspase-resistant
      GFP-labelled mutant of POM121 resisted degradation even in late apoptosis and was
      detected in clustered nuclear pores. Thus, it can be concluded that loss of
      POM121-GFP is a specific sensor of the activation of caspase-3-dependent
      proteolysis at the nuclear pores.

PMID- 15258470
TI  - Increase in the ratio of mitochondrial Bax/Bcl-XL induces Bax activation in human
      leukemic K562 cell line.
AB  - The p53- and Bcl-2-negative leukemic K562 cell line showed resistant to DNA
      damage-induced Bax activation and apoptosis. The constitutive balanced ratio of
      Bax/Bcl-XL in K562 mitochondria allowed the formation of active Bax and
      cytochrome c release from mitochondria in the presence of a BH3-only protein,
      tBid, in a cell-free system. Bax transfection led to Bax undergoing a
      conformational change, translocation to mitochondria and homo-oligomerization but
      not apoptosis in the K562 cell line. After treatment with UV light, while Bcl-XL
      but not Bax translocated to mitochondria in K562, both Bax and Bcl-XL
      translocated to mitochondria in the Bax stable transfectant K/Bax cells. The
      increased ratio of Bax/Bcl-XL in K/Bax mitochondria led to an increased
      conformationally changed Bax, formation of the homo-multimer of Bax-Bax, and a
      reduced hetero-dimerization of Bax-Bcl-XL. Increased proportion of active Bax was
      accompanied with increased percentage of apoptosis. We therefore demonstrate that
      direct increase in the ratio of mitochondrial Bax/Bcl-XL can induce Bax
      activation in the p53- and Bcl-2-negative leukemic cells. Increased Bcl-XL
      translocation and failure in Bax translocation from cytosol to mitochondria play
      important roles in preventing Bax activation.

PMID- 15258469
TI  - Tissue-specificity of apoptosis in hepatoma-derived cell lines.
AB  - Apoptosis is known to play a critical role in development and homeostasis in
      metazoans. Although apoptotic responses vary widely among cell types, the
      underlying mechanisms responsible for these differences are not known. In order
      to understand the molecular basis for these differences, we have studied a cell
      culture model comparing hepatoma cells to dedifferentiated cell lines derived
      from them. We recently reported evidence suggesting that a common regulatory
      locus affects both liver-specific function and sensitivity to lipopolysaccharide
      (LPS)-mediated apoptosis. Here, we show that dedifferentiated hepatoma cells
      undergo apoptosis in response to multiple compounds, including sorbitol (to
      induce hyperosmotic shock), TNF alpha and the microtubule damaging agent
      vinblastin. In contrast, the hepatoma parental cells fail to undergo apoptosis in
      response to any of the compounds tested. Further analysis of LPS-mediated cell
      death found that antioxidants N-acetylcysteine and alpha-tocopherol partially
      prevented apoptosis. Lastly, evidence is presented showing that LPS-mediated cell
      death of the hepatoma variant cell lines is caspase-dependent. These results
      suggest that pathways dictating hepatic phenotype also affect general cellular
      survival mechanisms in response to multiple agents. The dedifferentiated cells
      provide a model to examine the influence of cell-type specific expression on
      apoptotic signaling.

PMID- 15258471
TI  - Apoptotic cell death kinetics in vitro depend on the cell types and the inducers
      used.
AB  - INTRODUCTION: In vitro exposure of cells to a fluorochrome-labeled inhibitor of
      caspases (FLICA) labels cells after caspase activation and arrests further
      progress of apoptotic cell death. The labeled apoptotic cells can be quantified
      in relation to time of apoptosis induction with flow cytometry. Loss of membrane
      integrity (late apoptosis and cell death) was measured with exposure to propidium
      iodide (PI). From the labeling patterns with FLICA and PI the apoptotic cell
      death kinetics was calculated. METHODS: HL60 cells and human umbilical vein
      endothelial cells (HUVECs) were incubated in the presence of the fluorescent
      inhibitor of caspases, FAM-VAD-FMK (20 mM, FLICA) for up to 48 h. Apoptosis was
      induced by Camptothecin (CPT, 0.15 microM) or by a mixture of tumour necrosis
      factor alpha (TNF-alpha, 3 nM)-Cycloheximide (CHX, 50 microM). Samples were
      counterstained with PI. RESULTS: Incubation of HL60 cells with CPT induced
      apoptosis in 92% of cells within the first 18 h at a rate of 5% per hour while
      incubation with TNF-alpha/CHX resulted in apoptosis in 76% of the cells within
      the first 6 h at a rate of 12% per hour. Incubation of HUVECs with TNF-alpha/CHX
      induced apoptosis in 65% of the cells within the first 18 h at a rate of 3.7% per
      hour during the first 6 h of the incubation. During incubation with TNF-alpha/CHX
      the remaining viable HL60 cells and HUVECs entered apoptosis within 48 h at an
      approximate rate of 0.2 per hour. However, on the road of the cell death, HL60
      cells showed a transit from the viable (FLICA-/PI-) to early (FLICA+/PI-) and
      further to late apoptotic phase (FLICA+/PI+), while HUVECs entered directly from
      the viable to the late apoptotic stage. CONCLUSION: Apoptotic turnover rate
      depends on the stimulus used to induce apoptosis, while the type of the cell
      determines the way of the transition within the apoptotic cascade.

PMID- 15258472
TI  - Satisfaction with surgical outcomes and the phenomenology of embodiment.

PMID- 15258473
TI  - Understanding the meaning of satisfaction with treatment outcome.
AB  - OBJECTIVE: Although satisfying patients is an important goal in health care, what
      is meant by satisfaction in relation to treatment outcome is not clear. The
      objective of this study was to explore patients' perspectives on the meaning of
      satisfaction with treatment outcome. DESIGN: We conducted a qualitative
      exploratory study. SETTING: This study was conducted at an adult tertiary care
      hospital. PATIENTS: Individuals who had undergone elective hand surgery were
      included in this study. INTERVENTION: In-depth, open-ended interviews in which 31
      participants described their experience of a hand condition, how they evaluated
      the outcome of surgical interventions, and what it meant to be satisfied or
      dissatisfied with these outcomes were examined. ANALYSIS: : Interview transcripts
      were analyzed using Gadow's conceptualization of embodiment states: "object body"
      (disunity between the affected hand and the self) or "cultivated immediacy"
      (harmony between the hand and the self). RESULTS: Eight of 9 dissatisfied
      individuals were categorized as "object body" and 15 of 19 satisfied individuals
      were in, or in transition to, "cultivated immediacy". These states fluctuated and
      were also dependent on context (eg, social setting) and time since surgery.
      CONCLUSION: In relation to the outcome of hand surgery, satisfaction was
      experienced as a relative lack of tension between the patient's sense of self and
      the affected hand (ie, satisfaction was having a hand that could be lived with
      unself-consciously). Emotional and social effects of interventions and the
      influence of context should be considered in future measures of satisfaction with
      treatment outcome. Finally, interventions directed toward facilitating patients'
      experience of body-self unity could promote satisfaction with treatment outcome.

PMID- 15258474
TI  - Testing a new theory of patient satisfaction with treatment outcome.
AB  - OBJECTIVES: Theories of patient satisfaction with treatment outcome have not been
      developed and tested in healthcare settings. The objectives of this study were to
      test a new theory linking patient satisfaction and embodiment (body--self unity)
      and examine it in relation to other competing theories. DESIGN: We conducted a
      prospective cohort study. SETTING: This study was conducted at a tertiary care
      hospital. PATIENTS: We studied 122 individuals undergoing elective hand surgery.
      METHODS: Satisfaction with treatment outcome approximately 4 months after surgery
      was examined against the following factors (representing 7 theories of
      satisfaction): 1) overall clinical outcome, 2) patients' a priori self-selected
      important clinical outcomes, 3) foresight expectations, 4) hindsight
      expectations, 5) psychologic state, 6) psychologic state in those with poor
      outcomes, and 7) embodiment. ANALYSIS: Seven hypotheses were tested first using
      univariate analyses and then multivariable regression analysis. RESULTS:
      Satisfaction with treatment outcome was significantly associated with embodiment.
      Three confounders--the extent to which surgery successfully addressed patients'
      most important reason for surgery, hindsight expectations, and workers'
      compensation--were also significant. The final model explained 84% of the
      variance in a multidimensional measure of satisfaction with treatment outcome.
      CONCLUSION: This research suggests that satisfaction with treatment outcome could
      be facilitated by developing strategies to improve body--self unity, and
      eliciting and addressing the patient's most important reason for undergoing
      treatment.

PMID- 15258476
TI  - The impact of international medical graduate status on primary care physicians'
      choice of specialist.
AB  - BACKGROUND: Approximately one fourth of practicing physicians in the United
      States graduated from medical schools in other countries. It is unknown how the
      role of international medical graduate status affects physician decision-making.
      OBJECTIVE: The objective of this study was to determine whether a primary care
      physicians' knowledge of a specialist's international medical graduate status
      affects his or her decision to refer patients to that specialist. RESEARCH DESIGN
      AND SUBJECTS: We studied a national, cross-sectional study of primary care
      physicians who see adult patients. The sample was drawn from the American Medical
      Association Physician's Professional Data. Each physician received 2 clinical
      case vignettes describing a patient for whom referral to a specialist was
      considered necessary. Each vignette was followed by 5 vignette specialist
      descriptions with medical school graduate status varied randomly alongside other
      physician characteristics. MEASURE: We measured the decision to refer to an
      international versus U.S. medical graduate specialist. RESULTS: Of 1054 eligible
      physicians, 623 (59.1%) responded. Respondents were significantly more likely to
      refer to a U.S. medical graduate (USMG) compared with an international medical
      graduate (IMG) (63% vs. 54%, P <0.05). After adjustment for age, race, sex, and
      referral characteristics of the vignette specialists, a positive referral
      decision was noted in a higher proportion of vignettes in which the vignette
      specialist was described as a USMG versus an IMG (63% vs. 51%, P <0.05).
      CONCLUSION: With other factors being equal, vignette specialists described as
      IMGs versus USMGs were significantly less likely to be associated with a positive
      referral decision. Although specialist IMG status, relative to other factors,
      might not have a major effect on referral decisions, it is possible that negative
      views of international medical graduates could lead to suboptimal choices in
      referral decisions. Potentially, a patient could be referred to an USMG who
      happens to have inferior clinical skills than an IMG with superior clinical
      skills.

PMID- 15258475
TI  - Cost measurement in economic evaluations of health care: whom to ask?
AB  - PURPOSES: The purposes of this study were 1) to investigate the feasibility of
      using providers' administrative systems for the assessment of healthcare
      utilization in economic evaluations performed alongside multicenter studies, 2)
      to assess the convergent validity of patients' and providers' reports of care,
      and 3) to investigate whether differences between providers' and patients'
      reports are related to age, gender, health, recall period, and volumes of care.
      METHODS: Data were obtained as part of a cost-utility analysis alongside a
      multicenter clinical trial in patients with rectal cancer. For a sample of 179
      patients from 49 hospitals, data on hospitalizations, outpatient visits,
      medications, and care products during the first year after treatment were
      obtained from the patients by questionnaire or diary. For all patients, hospitals
      were contacted for information on hospitalizations and outpatient visits. For a
      subsample of 94 patients, 86 pharmacists and 10 suppliers of stoma care products
      were contacted for information on medications and care products. RESULTS:
      Response by providers of care was high, ranging from 84% to 100%. With respect to
      hospital days and outpatient visits, we found no significant differences between
      patients' and providers' reports. For medications and care products, agreement
      was lower, with providers reporting up to 2 times more product types and costs
      than patients. Providers failed to report 20% to 25% of all products, whereas
      patients failed to report 50% to 60% of all products. CONCLUSIONS: Patients'
      reports seem as valid as providers' reports for hospital days and outpatient
      visits. For medications and care products, we recommend the use of reports from
      providers of care, whenever feasible, because they much less underestimate
      volumes and costs than patients.

PMID- 15258477
TI  - Sensitivity of an AIDS case-finding algorithm: who are we missing?
AB  - OBJECTIVE: The objective of this study was to determine the sensitivity of an
      AIDS case-finding algorithm. METHOD: This study applied the AIDS case-finding
      algorithm to paid Medicaid claims linked to New Jersey AIDS surveillance data and
      assesses its sensitivity across subgroups of patients. FINDINGS: Of the 7183
      cases with confirmed AIDS, based on the state's registry information, 95% (n =
      6818) were correctly detected using all Medicaid claims, including pharmacy. For
      patients in a community-based waiver program, covered by Medicare, diagnosed with
      a severe mental illness, or continuously enrolled in Medicaid, with regular
      contact with the medical system, the algorithm identified almost all patients. To
      further evaluate algorithm performance, it was used with 2 groups of interest to
      researchers. For AIDS patients in the last 6 months of life, 88% were correctly
      detected without use of pharmacy claims and 95% when pharmacy claims were
      included. For pregnant women, data from the 6 months before the latest delivery
      date identify 27% of pregnant women without pharmacy claims and 41% when pharmacy
      claims were included. Using claims made after the latest delivery date, 81% of
      pregnant women were detected without pharmacy claims and 93% when pharmacy claims
      were included CONCLUSION: Results demonstrate that a multilevel screen can be
      used with Medicaid claims to effectively to detect most patients with AIDS.
      Detection is lower for some subgroups, and the absence of pharmacy claims can
      compromise detection.

PMID- 15258478
TI  - A pilot trial of a telecommunications system in sleep apnea management.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is an effective therapy
      for obstructive sleep apnea syndrome (OSAS), although many patients have
      difficulty adhering to this therapy. The purpose of this study was to investigate
      the effectiveness of totally automated telephone technology in improving
      adherence to prescribed CPAP therapy. RESEARCH DESIGN: This pilot study was a
      randomized clinical trial in 30 patients being started on CPAP therapy for OSAS.
      Patients were randomly assigned to use of a computer telephone system designed to
      improve CPAP adherence (telephone-linked communications for CPAP [TLC-CPAP]) in
      addition to usual care (n = 15) or to usual care alone (n = 15) for a period of 2
      months. TLC-CPAP is a computer-based system that monitors patients' self-reported
      behavior and provides education and reinforcement through a structured dialogue.
      MEASURES: A sleep symptoms checklist and the Functional Outcomes of Sleep
      Questionnaire were administered at study entry and at 2-month follow up. Hours of
      CPAP use at effective mask pressure were measured by the CPAP device, stored in
      its memory, and retrieved at the 2-month visit. RESULTS: At 2 months, patients
      randomized to TLC-CPAP had fewer reported sleep-related symptoms (9.4 vs. 13.4, P
      = 0.047) than those receiving usual care. The average nightly CPAP use in the TLC
      CPAP group was 4.4 hours compared with 2.9 hours (P = 0.076) in the usual-care
      group. CONCLUSIONS: This pilot study suggests that patients with OSAS started on
      CPAP and a concurrently administered automated education and counseling system
      had better CPAP adherence and better control of OSAS symptoms.

PMID- 15258479
TI  - Relationship between general practitioner certification and characteristics of
      care.
AB  - BACKGROUND: The introduction of mandatory or quasimandatory certification
      processes for general/family doctors has become common in many countries,
      including Australia. Whether certification effects the care provided is rarely
      investigated. OBJECTIVES: The objective of this study was to determine whether
      certification of general/family physicians is associated with clinical
      performance. RESEARCH DESIGN: We conducted a secondary comparative analysis of
      data from an Australian national cross-sectional survey (April 2000-March 2002).
      SUBJECTS: Subjects consisted of a random sample of 1982 general practitioners
      (GPs) METHODS: Each participant provided demographic details and information
      about 100 consecutive patient encounters (total 197,500). We compared
      characteristics of certified and uncertified general practitioners (GPs), their
      patients, encounters, problems, management actions, and tested 34 performance
      indicators. We investigated whether differences identified in descriptive
      analyses were explained by other factors. RESULTS: Of 1975 GPs who indicated
      certification status, 659 (33.4%) were vocationally certified. Certificants were
      more likely to be female, younger, Australian graduates, working fewer sessions,
      in larger practices, in accredited practices, and using computers for clinical
      purposes. Their patients were younger, more often female, and less likely to hold
      a healthcare concession card. Their consultations were longer; they prescribed
      fewer medications and more clinical treatments and procedures, ordered more
      pathology tests, and referred more to other health professionals. After
      adjustment for GP/practice, patient and morbidity differences, certificants had
      longer consultations, did more therapeutic procedures, prescribed less overall,
      prescribed fewer nonsteroidal antiinflammatory drugs in the elderly, and fewer
      antibiotics for upper respiratory infections. CONCLUSION: Certification of
      general practitioners has a significant association with consultation behavior
      and patient management.

PMID- 15258480
TI  - Social support and risk-adjusted mortality in a frail older population.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that social
      support is an important predictor of mortality in a frail older population
      receiving formal long-term care services. RESEARCH DESIGN AND METHODS: The
      analysis is based on 3138 individuals enrolled in 28 Programs of All-Inclusive
      Care for the Elderly (PACE). Information about the enrollees is obtained from
      dataPACE. Semiparametric Cox proportional hazards models are estimated to assess
      the importance of individual risk factors, program effect, and social support.
      RESULTS: The introduction of the social support variables into the mortality
      model containing the sociodemographic, health needs, and the PACE-site indicator
      variables results in a significant improvement of the overall model fit. Several
      social support variables are statistically significant predictors of mortality.
      Controlling for all participant and caregiver characteristics, participants whose
      caregiver is a spouse have a significantly lower risk of mortality (hazard ratio
      = 0.63) compared with those whose caregiver is not a spouse. Furthermore,
      caregivers' assistance with meals confers a significantly lower risk of morality
      (hazard ratio = 0.66) compared with no assistance with meals. CONCLUSIONS: This
      study shows that certain aspects of informal caregiving are important factors
      enhancing survival in a population of frail, nursing home-certifiable individuals
      enrolled in a health program that already provides extensive services, including
      personal care, chores, and meals. Further research to better differentiate
      between the affective versus the instrumental dimensions of social support is
      needed to guide programs on how to balance the use of resources to provide both
      the necessary formal services and the support for the informal caregivers.

PMID- 15258482
TI  - Validity of procedure codes in International Classification of Diseases, 9th
      revision, clinical modification administrative data.
AB  - BACKGROUND: Administrative hospital discharge data are widely used to assess
      quality of care in patients undergoing certain procedures. However, little is
      known about the validity of administrative coding of procedure data. We conducted
      a detailed chart review to evaluate the accuracy and completeness of information
      on procedures in administrative data. METHODS: We randomly selected 1200 hospital
      separations in the period April 1, 1996, to March 31, 1997, from administrative
      discharge data of 3 acute adult hospitals in Calgary, Alberta, Canada. Each
      separation record in administrative data contains up to 10 procedure coding
      fields. The corresponding medical charts were reviewed for recording presence or
      absence of procedures. We then determined sensitivity to quantify the accuracy of
      coding presence of procedures in administrative data when these are present in
      the chart data (criterion standard). RESULTS: The agreement between the 2
      databases varied greatly across 35 procedures studied. The sensitivity ranged
      from 0% to 94%. Of 6 major procedures studied, validity of coding was generally
      good, with 5 procedures having coding sensitivity of 69% and over and only 1
      (lysis of peritoneal adhesion) with a low sensitivity of 41%. In contrast, many
      minor procedures had low sensitivities. Of 29 minor procedures studied,
      sensitivity was lower than 50% for 15 procedures, between 50% and 79% for 10, and
      80% and over for 4. CONCLUSION: Validity of information on procedures in
      administrative discharge data appears to be related to type of procedures. Major
      procedures that are usually performed in operating rooms are reasonably well
      coded. Meanwhile, minor procedures that are routinely performed on wards or in
      radiology departments are generally undercoded.

PMID- 15258481
TI  - Understanding the factors underlying disparities in cancer screening rates using
      the Peters-Belson approach: results from the 1998 National Health Interview
      Survey.
AB  - BACKGROUND: Cancer screening rates vary substantially by race and ethnicity. We
      applied the Peters-Belson approach, often used in wage discrimination studies, to
      analyze disparities in cancer screening rates between different groups using the
      1998 National Health Interview Survey. METHODS: A regression model predicting the
      probability of getting screened is fit to the majority group and then used to
      estimate the expected values for minority group members had they been members of
      the majority group. The average difference between the observed and expected
      values for a minority group is the part of the disparity that is not explained by
      the covariates. RESULTS: The observed disparities in colorectal cancer screening
      (5.88%) and digital rectal screening (8.54%) between white and black men were
      explained fully by the difference in their covariate distributions. Only half of
      the disparity in the observed screening rates (13.54% for colorectal and 17.47%
      for digital rectal) between white and Hispanic men was explained by the
      difference in covariates between the groups. The entire disparity observed in
      mammography screening rates for black and Hispanic women (2.71% and 6.53%,
      respectively) compared with white women was explained by the difference in
      covariate distributions. CONCLUSIONS: We found that the covariates that explain
      the disparity in screening rates between the white and the black population do
      not explain the disparity between the white and the Hispanic population. Knowing
      how much of a health disparity is explained by measured covariates can be used to
      develop more effective interventions and policies to eliminate disparity.

PMID- 15258483
TI  - Improving identification of Hispanic males in Medicare: use of surname matching.
AB  - OBJECTIVES: Medicare administrative and claims files maintained by the Centers
      for Medicare and Medicaid Services (CMS) are frequently used to examine racial
      and ethnic disparities in healthcare use. However, identification of Hispanic
      ethnicity for beneficiaries in the Medicare claims files is problematic, greatly
      limiting the use of these administrative data for examining race/ethnicity
      differences. This article reports on 2 studies assessing the effectiveness of a
      Hispanic surname match for improving the accuracy of race/ethnicity codes for
      elderly males in the Medicare data sets. METHODS: Study 1 used survey data to
      compare a Medicare race code + Spanish surname composite indicator to self
      identification as Hispanic. Study 2 used Medicare administrative files and U.S.
      Census 2000 data to identify how well the Medicare race code alone and the
      Medicare race code + Spanish surname composite indicator compared with estimates
      obtained from census data for 16 U.S. counties dispersed across 5 states.
      RESULTS: Using self-identification as the gold standard, including the Spanish
      surname match increased accuracy for Hispanics and whites compared with the
      Medicare race code alone. The Spanish surname match also dramatically improved
      the Medicare code's estimation of elderly Hispanic and white males compared with
      county-level census data. CONCLUSIONS: Augmenting the Medicare race code with a
      match to Spanish surnames yields substantial improvement in the identification of
      elderly Hispanic and white non-Hispanic male Medicare beneficiaries. Using
      surname information to supplement the Medicare race code could greatly enhance
      researchers' ability to examine healthcare equity.

PMID- 15258484
TI  - Economies of scale in institutional review boards.
AB  - BACKGROUND: Research with human subjects is essential for most clinical and
      social science research. As such, the ethical treatment of subjects, including
      the role of Institutional Review Boards (IRBs), is of paramount concern. The
      prevailing system of IRBs in the United States reflects an integrated approach in
      which research organizations have their own local IRB. Recent regulatory changes
      and a few high-profile problems have prompted proposals for greater investments
      in IRBs. OBJECTIVES: We conducted regression analyses, looking at how IRB size
      was associated with IRB costs (economies of scale). RESEARCH DESIGN: We studied
      data from a cross-sectional survey. SUBJECTS: We studied IRBs at Veterans Affairs
      (VA) and VA-affiliated medical centers (n = 109); 81 (73%) IRB administrators
      completed the survey. Fourteen of the administrators had missing data and were
      excluded from final analysis, leaving a sample of 67. MEASURES: The primary
      dependent variable was IRB costs in 2001, which we estimated from the survey.
      Independent variables included IRB size measured as the number of actions (ie,
      number of initial reviews, amendments, continuing/annual reviews, and
      harms/adverse event reports) reviewed by the IRB in the last year. RESULTS: The
      results indicate that very large economies of scale exist, especially for IRBs
      that handle fewer than 150 actions per year. CONCLUSIONS: A discussion of the
      costs of benefits of having 3000 to 5000 local IRBs in the United States is
      warranted because other organizational arrangements could be economically and
      socially advantageous.

PMID- 15258486
TI  - Multidetector computed tomography technology: current status and emerging
      developments.
AB  - By virtue of its speed and isotropic resolution of thin slices, multidetector-row
      computed tomography (MDCT) offers unique advantages over previous single-detector
      row CT, with improved temporal and spatial resolution. This review describes the
      historical perspective and growth trends of MDCT scanners and highlights the
      current status and emerging developments in multidetector technology based on
      presentations at the symposium "Advances in Multidetector CT," under the auspices
      of the Institute for Advanced Medical Education in Washington, DC.

PMID- 15258487
TI  - Computed tomography contrast enhancement principles and the use of high
      concentration contrast media.
AB  - Numerous pharmacokinetic and physiologic interactions are involved in the
      utilization of iodinated contrast in computed tomography. Patient related
      factors, injection related variables including contrast material concentration,
      and intravascular and organ specific imaging techniques are but a few of the
      principles that must be understood. With the advancement of faster CT scanners,
      these factors must be considered for optimal contrast enhancement.

PMID- 15258488
TI  - Advances in multidetector computed tomography: applications in neuroradiology.
AB  - The improvement in multidetector computed tomography has had a tremendous impact
      on neuroimaging. Some of these strides include imaging in the setting of acute
      stroke with the advent of perfusion computed tomography, and studying
      intracranial aneurysms and, to some extent, carotid artery disease. The purpose
      of this article is to review these applications as they were outlined at the
      "Advances in Multidetector CT" meeting held in Washington, DC, September 13-14,
      2003.

PMID- 15258489
TI  - Abdominal imaging with multidetector computed tomography: state of the art.
AB  - This article is based on lectures which were given at the Multidetector Computed
      Tomography Conference in Washington, D.C. on September 13-14, 2003. Specifically,
      this article summarizes the Abdominal Imaging Section of this meeting. It is not
      an exhaustive review, but it rather attempts to highlight key points related to
      preoperative MDCT of the liver, MDCT of pancreas, MDCT urography and MDCT of
      thoracoabdominal and spinal trauma.

PMID- 15258490
TI  - Multidetector computed tomography and blunt thoracoabdominal trauma.
AB  - Computed tomography has had an increasing role in the evaluation of patients
      after blunt trauma. Important findings in thoracic trauma include acute traumatic
      aortic injury, pneumothorax, hemothorax, pulmonary contusions and lacerations,
      mediastinal hematoma, and diaphragmatic rupture. The solid abdominal viscera may
      lacerate; infarct; or suffer vascular, ductal, or pyelocalyceal disruption. The
      bladder and intestines may rupture. In abdominal pelvic trauma, the direction of
      applied force often results in an identifiable constellation of injuries. This
      article reviews how multidetector computed tomography (MDCT) is used in the
      trauma patient. Technical advances of increased cephalocaudad coverage speed and
      improved z-axis resolution intrinsic to MDCT, together with effective contrast
      utilization, make MDCT invaluable in the setting of trauma.

PMID- 15258491
TI  - Multidetector computed tomography imaging of the spine.
AB  - This article discusses applications of multidetector computed tomography imaging
      of the spine as they were presented at the "Advances in Multidetector CT" meeting
      held in Washington, DC, September 13-14, 2003. These include imaging the spine in
      the setting of trauma, postoperative fusion, chronic pain, radiculopathy, or bony
      lesions and performing image-guided biopsies.

PMID- 15258492
TI  - Computed tomography angiography: state-of-the-art imaging using multidetector-row
      technology.
AB  - Multidetector-row computed tomography (MDCT) is an essential diagnostic modality
      for many clinical algorithms. This is particularly true with regard to the
      evaluation of cardiovascular disease. As a result of increased image acquisition
      speed, improved spatial resolution, and greater scan volume, MDCT angiography
      (computed tomography angiography [CTA]) has become an excellent noninvasive
      imaging technique, replacing intra-arterial digital subtraction angiography for
      most vascular territories. The clinical success of CTA depends on precise
      synchronization of image acquisition with optimal vascular enhancement. As
      technology continuously evolves, however, this task can be challenging. It
      remains important to have a fundamental knowledge of the principles behind
      technical parameters and contrast medium administration. This article reviews
      these essential principles, followed by an overview of current clinical
      applications.

PMID- 15258493
TI  - Radiation exposure and projected risks with multidetector-row computed tomography
      scanning: clinical strategies and technologic developments for dose reduction.
AB  - A substantial increase in computed tomography (CT) scanning with availability of
      state-of-the-art multidetector-row CT scanners has generated debate about its
      safety and considerable interest in formulating clinical and technologic
      strategies to reduce radiation exposure. This review describes the magnitude of
      radiation exposure associated with CT scanning and projected radiation risks as
      well as clinical strategies and major technologic innovations for reducing
      radiation dose to patients undergoing CT scanning.

PMID- 15258494
TI  - New aspects on critical care medicine training.
AB  - Recently, three fundamental changes have been introduced in medical education,
      all of particular importance to critical care medicine: (1) clinical teaching and
      medical practice now emphasize evidence-based medicine, (2) patient safety
      aspects are increasingly stressed, and (3) use of simulation in medical training
      is spreading rapidly. In 1999, the disturbingly high frequency of life
      threatening or even lethal medical complications was emphasized by the Institute
      of Medicine in the book To Err Is Human. The Institute of Medicine recommended
      establishing interdisciplinary team training programs incorporating efficient
      methods such as simulation. Although simulation has been used by the aviation
      industry and the military for several decades, only during the past decade has
      this become a teaching method in medicine. Currently, two full-scale computerized
      simulators are available: METI, provided by Medical Education Technologies,
      Sarasota, Florida, and SimMan, manufactured by Laerdal Medical, in Stavanger,
      Norway. The simulation center at the University of Pittsburgh Medical Center was
      established in 1994 and has grown quickly to its current large facility, where,
      in academic year 2003 to 2004, approximately 8000 healthcare professionals were
      trained on the SimMan. Courses taught include clinical procedures and decision
      making in perioperative medicine, acute medicine, pharmacology, anesthesiology,
      airway management, bronchoscopy, pediatric versus adult crisis management,
      critical events in obstetrics, and crisis team training. Advantages of simulation
      training over traditional medical education methods include (1) provision of a
      safe environment for both patient and student during training in risky
      procedures, (2) unlimited exposure to rare but complicated and important clinical
      events, (3) the ability to plan and shape training opportunities rather than
      waiting for a suitable situation to arise clinically, (4) the ability to provide
      immediate feedback, (5) the opportunity to repeat performance, (6) the
      opportunity for team training, and (7) lower costs, both direct and indirect.
      Within the next decade, use of computerized simulators for evidence-based
      education and training in medicine is expected to develop considerably and spread
      rapidly into a very important domain of medical schools throughout the entire
      world.

PMID- 15258495
TI  - Medical technology in the intensive care unit.

PMID- 15258496
TI  - Personal commentary on the diagnosis and treatment of circulatory shock states.

PMID- 15258497
TI  - Sepsis: current status, future prospects.

PMID- 15258498
TI  - Advances in the understanding of acute respiratory distress syndrome: summarizing
      a decade of progress.

PMID- 15258499
TI  - Acute respiratory distress syndrome, the critical care paradigm: what we learned
      and what we forgot.
AB  - In the last several years, we definitely learned that the acute respiratory
      distress syndrome lung is small, nonhomogeneous, and that mechanical ventilation
      in this baby lung may cause physical damage as well as inflammatory reaction. The
      clinical benefit of the gentle lung treatment, based on a decrease of
      global/regional stress and strain into the lung, has been finally proved.
      However, we forgot the importance of lung perfusion and its distribution in this
      syndrome and, besides a low tidal volume, we still do not know how to handle the
      other variables of mechanical ventilation. Measurements of variables as
      transpulmonary pressure and end expiratory lung volume, for a rational setting of
      mechanical ventilation, should be introduced in routine clinical practice.

PMID- 15258500
TI  - Research: advances in cell biology relevant to critical illness.
AB  - During the past decade, enormous advances have been made in cell biology. Major
      advances included the publication of the human genome sequence, the development
      of proteomics, and DNA microarray technologies and techniques to selectively
      "silence" genes using short strands of double-stranded RNA. Some areas of great
      progress that are particularly relevant to critical care medicine include huge
      improvements in our understanding of the signal transduction pathways involved in
      the innate immune response and adaptation to hypoxia. Other areas of important
      progress include improvements in our understanding of how inflammation causes
      derangements in epithelial structure and function and impairs cellular
      utilization of oxygen.

PMID- 15258501
TI  - Ethical issues in the intensive care unit.

PMID- 15258502
TI  - Critical care in difficult areas.
AB  - Critical care in India has grown very rapidly in the past decade. The Indian
      Society of Critical Care Medicine has developed into a strong national body that
      has established its own journal, academic program, and Web site. Its annual
      national congresses are well organized and very well attended and have a high
      degree of academic content. International publications have started coming out of
      India despite limitations. International recognition of the standards of critical
      care in India has begun. Besides other common patients seen everywhere, those
      with tropical diseases form a significant group of patients in Indian ICUs.
      Development of guidelines, starting formal training through a certificate course,
      and formation of a resuscitation council have been some of the other achievements
      of Indian Society of Critical Care Medicine. A number of problems still exist in
      the field of critical care in India. Considering that India as a portal for
      medical tourism, growth of this field is expected in the next decade.

PMID- 15258503
TI  - Intensive care in developing countries in the Western Pacific.
AB  - The rapid economic, scientific, and technologic development in Asia probably is
      the most important in the world today. Eventually, the development of health care
      and critical care medicine in the Western Pacific will be affected. Even with the
      problems that have to be faced, the future of critical care medicine in the
      region looks promising.However, the leaders of critical care medicine in each
      country should identify the model of intensive care practice that is the most
      appropriate for their country. Each country needs to assign an appropriate rank
      of priority to intensive care. There is a great need for simple, inexpensive
      therapeutic interventions and methods for monitoring critically ill patients that
      can be shown to be effective. Efficient systems for transporting critically
      patients are also needed. Simple ventilators with inexpensive monitors and
      defibrillators are the technology that is most needed. Good referral systems and
      greater use of physician extenders, such as nurse practitioners, to provide
      enhanced access to specialist care for critical illness should be promoted. A few
      high-standard ICUs with good facilities for education and training should be
      organized on a regional basis in each country.

PMID- 15258504
TI  - [The frequency and impact of skin diseases in France].

PMID- 15258505
TI  - ["Bilan": a word to be banished! But what about the "bilan" itself?].

PMID- 15258506
TI  - [Relationship between clinical findings of patients with bullous pemphigoid and
      antigens recognized by their circulating antibasement membrane zone antibodies].
AB  - INTRODUCTION: Clinical features and extent of bullous pemphigoid lesions differed
      widely among patients. The pathogenic role of anti-BPAG2 antibodies has been
      recently demonstrated. The aim of this study was to analyze the relationship
      between clinical features of bullous pemphigoid patients and the antigens
      recognized by their serum. PATIENTS AND METHODS: One hundred and twelve bullous
      pemphigoid patients were included in this prospective multicenter study.
      Inclusion criteria were the following: 1) diagnosis of bullous pemphigoid
      established on the presence of 3 of the 4 clinical features of bullous
      pemphigoid, histological picture of bullous pemphigoid and positive direct
      immunofluorescence; 2) serum available for immunoblotting studies. The clinical
      and biological findings were prospectively recorded on standard forms. Sera were
      collected and analyzed using indirect immunofluorescence and immunoblotting on
      human epidermal extracts. RESULTS: Analysis of patient's clinical features
      depending on the antigens recognized by their serum showed that patients whose
      serum contained anti-BPAG1 antibodies had more frequently pruritus, blisters on
      the lower limbs and a positive indirect immunofluorescence. Patients whose serum
      contained anti-BPAG2 antibodies had blisters more frequently localized on the
      head, and a more frequently negative indirect immunofluorescence. Patients whose
      serum was negative by immunoblotting had less frequently urticarial and/or
      eczematous lesions, bullae less frequently localized on the lower part of the
      trunk, abdomen and lower limbs, lower eosinophilia and a more frequently negative
      indirect immunofluorescence. CONCLUSION: Patients with circulating anti-BPAG1
      antibodies exhibited the most typical, clinical and biological features of
      bullous pemphigoid.

PMID- 15258507
TI  - [Frequency of associated malignancies in cutaneous lymphomas: a retrospective
      study of 86 cases].
AB  - INTRODUCTION: The initial staging and follow-up of cutaneous lymphomas is far
      from being standardized. In this retrospective study, we describe the results of
      systematic laboratory investigations dedicated to a better definition of the TNM
      stage for the detection of associated malignancies. PATIENTS AND METHODS: This
      was a retrospective, descriptive, single centre study, including all cases of
      cutaneous lymphomas seen in the department of dermatology, university hospital of
      Reims, between 1987 and 2001. Data systematically recorded for each patient
      included clinical, biological, histological and molecular (cutaneous or
      circulating T or B clone) findings, imaging (thoracic and abdominal computed
      tomography scan; or chest X-ray and abdominal ultrasound tomography) and bone
      marrow histology (for B-cell cutaneous lymphomas only). RESULTS: In cutaneous T
      cell lymphomas (n=63 including 47 mycosis fongoides), imaging revealed deep lymph
      nodes in 4 cases, a carcinoma of the kidney in one case, and a benign tumour in 6
      cases. A T-cell clone was detected in the skin in 19/33 cases and in peripheral
      blood in 17/31 cases. In cutaneous B-cell lymphomas (n=23), imaging showed
      splenomegaly in 2 cases, a B-cell clone was detected in 3/12 cases in the skin,
      and bone marrow histology was normal in 21/22 cases. Among patients with
      cutaneous T-cell lymphomas, 14/63 (22 p. 100) had an associated malignancy. In
      8/14 cases, the diagnosis of the associated malignancy was made prior to that of
      the cutaneous T-cell lymphoma. In 4 cases, the interval between the previous
      malignancy and the diagnosis of lymphoma was <or=2 Years, and in 2 other cases
      the malignancy was discovered on the occasion of the staging of the T-cell
      cutaneous lymphoma. CONCLUSION: Laboratory investigations in cutaneous lymphomas
      are necessary to research deep lymph nodes, especially in case of high stage T
      cell lymphomas. In exceptional cases they can reveal an associated malignancy,
      which is usually detected by clinical examination. In cutaneous B-cell lymphoma,
      bone marrow histology or cytology is generally normal hence may not be justified
      in low grade or localized cutaneous B-cell lymphomas.

PMID- 15258508
TI  - [Squamous cell carcinoma on a leg ulcer in the West Indies].
AB  - INTRODUCTION: The epidemiology of carcinoma developing on a leg ulcer is poorly,
      although high incidence rates are reported in Africa. PATIENTS AND METHODS:
      Retrospective study of cases reported in Guadeloupe, a tropical country with a
      large population from African descent and with high quality health care level.
      RESULTS: Sixteen cases, mean age 71, were diagnosed over a 10-Year period in the
      only referral hospital. The annual incidence was an estimated 0.4/100,000.
      Preceding ulcers had a long course (mean of 27 Years) and had various causes.
      Social distress was the rule (14/16 patients). One third of the clearly
      differentiated (15/16) squamous cell-type tumors exhibited metastatic extension
      on presentation. At Year 3, the mortality rate was of 40 p. cent. The best
      survival rate (6 remissions/8 cases) was associated with primary limb amputation.
      DISCUSSION: Malignant ulcers appeared more frequent in Guadeloupe than in the
      influent countries of the North, but with an instance 4-fold lower than in
      Africa. Like many other tropical diseases, socio-behavioral factors may play a
      major role.

PMID- 15258510
TI  - [Strip papular mucinosis associated with systemic sclerosis].
AB  - INTRODUCTION: Other than discreet infra-clinical mucinous deposits observed
      during many inflammatory dermatoses, clinically visible dermal mucinosis can
      sometimes be associated with collagenosis. It is usually lupus and very rarely
      scleroderma. In this case, no confusion with papular mucinosis must be made. CASE
      REPORT: A 51 year-old woman presented with infiltrated erythematous lesions in
      strips on the inner sides of the thighs and legs, associated with myalgia,
      arthralgia and puffy fingers. Mixed connective tissue disease was the initial
      diagnosis. The clinical picture was rapidly completed by sclerodactylia,
      telangiectasia, a Raynaud's syndrome and esophageal involvement leading to the
      diagnosis of CREST-type systemic scleroderma. The biopsy of the erythematous
      strip lesions revealed a dermal mucinosis. Treatment with hydroxychloroquine led
      to the regression of the mucinous lesions and the stabilization of the
      scleroderma, which, four years later, had not developed further. DISCUSSION:
      Dermal mucinosis can accompany lupus erythematosus, in rare cases dermatomyositis
      and, in exceptional cases, scleroderma. The clinical presentation varies with
      large infiltrated plaques, reticulated or papulo-nodular lesions. Conversely,
      strip lesions such as those observed in our patient have never been reported till
      now. The association of a localized dermal mucinosis and a scleroderma must not
      lead to the erroneous diagnosis of papular mucinosis of clearly differing
      prognosis. The occurrence of a mucinosis during collagenosis might be related to
      enhanced synthesis of mucin by the fibroblasts mediated by the inflammatory
      cytokines, increased in this context.

PMID- 15258509
TI  - [Becaplermin gel (Regranex gel)].
AB  - Becaplermine gel (Regranex) is an hydrogel which contains 100 microg of Platelet
      Derived Growth Factor-BB (rhPDGF-BB) per gram. Regranex is presented in 15-gram
      multidose tubes. It has been approved as adjuvant treatment for neuropathic
      diabetic ulcerations of less than 5 cm2, extending into the subcutaneous tIssue,
      in the absence of ischemia, in conjunction with a standardised program of
      appropriate wound care, (control of infection, sharp debridement, provision of a
      moist environment and avoidance of pressure on the wound). PDGF-BB promotes
      cutaneous wound healing by increasing proliferation and migration of dermal
      fibroblasts and extracellular matrix deposition. PDGF also promotes chemotaxis of
      neutrophils, monocytes and smooth muscle cells in wounds. Topical application of
      rhPDGF-BB speeds wound healing and promotes granulation tIssue formation,
      synthesis of extracellular matrix and the inflammatory phase of the wound healing
      process in healthy and healing-impaired animal models. In clinical trials in
      humans, accelarated healing has been demonstrated in patients with lower
      extremity diabetic neuropathic ulcers and decubitus sores by increasing
      granulation tIssue formation and epithelialization. Local toxicity studies in
      humans were negative (repeated becaplermin gel application under occlusion to
      intact or abraded skin, dermal sensitization tests). Pharmacokinetic studies in
      humans have shown that systemic absorption after topical applications was
      minimal. In trials, systemic and local tolerance were excellent. Reported adverse
      effects were similar in incidence and in nature in all groups. The 0.01% Regranex
      gel is safe and easy to use, with single daily application. It is currently the
      only commercially available topical growth factor for use in cutaneous wound
      healing.

PMID- 15258511
TI  - [Photodistribution of varicella in an adult].
AB  - INTRODUCTION: Exacerbation of viral exanthema has been described after different
      types of aggression such as sun exposure. Photoaggravation of varicella is
      unusual. CASE REPORT: We report the case of a 25 year-old woman who presented
      with varicella mainly distributed on the neckline and the top of the back. During
      the viral incubation she had been sunburnt in these areas. DISCUSSION: The
      clinical lesions and the evolution of a photoaggravated varicella differs from
      those of classical varicella. The vesicles are selectively distributed on areas
      previously sunburned or suntanned. The more tanned or more erythematous the area
      is, the greater the number of lesions. They are often at the same stage of
      development and the course can be shortened with only one or two progressive
      phases. Inflammatory modifications secondary to ultraviolet exposure induces in
      photoexposed areas an increase in vascular flow and also an increase in capillary
      permeability, which can promote diapedesis of the lymphocytes or the transit of
      viral particles. Therefore, sun exposure during the incubation of the virus can
      enhance the deposit of viral pArticles in the cutaneous areas submitted actinic
      stress. The amount of virus in sun exposed areas is greater than in the non
      exposed ones.

PMID- 15258512
TI  - [Particular histological features of a case of Sweet's syndrome induced by G
      CSF].
AB  - BACKGROUND: Sweet's syndrome may occur during medullar aplasia, especially after
      treatment with exogenous growth factors such as G-CSF. In this context, Sweet's
      syndrome presents particular histological features that we detail in this
      observation. CASE REPORT: A 50 year-old man was treated for multiple myeloma with
      a mobilizating chemotherapy prior to autologous stem cell transplantation. Four
      days after the onset of G-CSF, he presented with a febrile generalized eruption
      of erythematous infiltrated lesions. Histological examination of a skin biopsy
      showed a neutrophilic infiltrate associated with atypical xanthomized histiocytes
      and vascular hyperplasia with marked endothelial turgescence. Treatment with a
      short cause of oral corticosteroids was efficient. DISCUSSION: The classical
      histological features of Sweet's syndrome consist in a dermal neutrophilic
      infiltrate with edema. In our patient, we noticed the presence of atypical
      histiocytes among the dermal neutrophilic infiltrate. These histiocytes are
      described in maculo-papular eruptions induced by G-CSF, and should not be
      confused with a malignant infiltrate associated with a hemopathy. Vascular
      hyperplasia may be related to the angiogenic properties of G-CSF. Knowledge of
      these histological features would enable clinicians and histologists to recognize
      the appropriate diagnosis.

PMID- 15258513
TI  - [Late onset of a chronic septic granulomatous disease].
AB  - INTRODUCTION: Chronic septic granulomatosis is a disease characterized by an
      impaired bactericidal potential of the neutrophilic polynuclear. The cutaneous
      manifestations rarely reveal the disease, but are of considerable interest in the
      diagnosis, notably during the late onset forms. We report such a case. CASE
      REPORT: A 15 year-old girl, born of consanguine parents, had a history of
      visceral leishmaniasis and hepatic hydatidosis. For the past 3 years she had
      developed dermatitis lesion on the face and skin folds, chronic folliculitis and
      suppurating axillary and inguinal lymphoadenitis. The absence of a reduction in
      tetrazolium nitro blue led to the diagnosis of chronic septic granulomatosis.
      Prophylactic treatment stabilized the cutaneous lesions. DISCUSSION: Chronic
      septic granulomatosis regroups various severe and recurrent manifestations. Its
      transmission is usually X-linked recessive or, on rare occasions, autosomal
      recessive. The clinical manifestations leading to the diagnosis are often of very
      early onset. They are principally pneumonia due to apergillus fumigatus and
      lymphoadenitis. Cutaneous involvement, although less common, must not be
      neglected because it can lead to the diagnosis of late onset forms, as in our
      patient.

PMID- 15258514
TI  - [Adenocarcinoma of the umbilicus].
AB  - INTRODUCTION: Most of the umbilical neoplastic processes are metastatic whereas
      primary adenocarcinoma is scarce and hard to distinguish from a secondary
      process. Our observation illustrates this difficulty. OBSERVATION: A fifty year
      old woman had developed chronic omphalitis over several years. She consulted for
      a multinodular, erythemato-violine, oozing and deep infiltrating tumor of the
      umbilicus which had been developing for two months. The anatomopathological
      exploration of a biopsy of the lesion suggested a clearly differentiated
      adenocarcinoma whose digestive origin was the most likely. Investigations for a
      primary neoplasm were negative. Polychemotherapy was efficient with eight months
      recline. DISCUSSION: Umbilical metastases are referred to as Sister Marie Joseph
      nodule. They essentially correspond to a metastatic localization of an intra
      abdominal adenocarcinoma. The major problem consists in distinguishing a Sister
      Marie Joseph nodule where the neoplasm remains indefinite from an adenocarcinoma
      developed from an embryonic remainder. The existence in our patient's case
      history of a chronic omphalitis developing for Years and the negative tests for a
      primary neoplasm suggest a primary adenocarcinoma of the umbilicus.

PMID- 15258515
TI  - [Fixed drug eruption induced by sulfaguanidine].
AB  - INTRODUCTION: Fixed drug eruption is a lesion induced by drugs. The family of
      drugs usually incriminated are sulfonamides, tetracyclines and pyrazols. We
      describe nine cases of fixed drug eruption induced by sulfaguanidine, a
      sulfonamide with local action. CASE REPORTS: All the patients presented one or
      more fixed drug eruption reactivation lesions induced by sulfaguanidine as self
      medication for diarrhea. The number of lesions increased in 7 cases after
      reactivation. The delay in occurrence of the fixed drug eruption decreased during
      the different episodes. The lesions predominated on the hands in 8 cases of 9.
      DISCUSSION: The sulfaguanidine must be added to the list of drug-induced fixed
      drug eruptions with limited absorption from the gastrointestinal tract.

PMID- 15258516
TI  - [Isotretinoin and increase in breast volume].

PMID- 15258517
TI  - [Treatment of actinic keratosis with topical imiquimod (Aldara): the cutaneous
      erosion appears beneficial].

PMID- 15258518
TI  - [Superficial granulomatous pyoderma associated with an adenocarcinoma of the
      colon].

PMID- 15258519
TI  - [Painful erythema of the forefoot].

PMID- 15258520
TI  - [Vesicular-bullous lesion of a finger followed by disseminated eruption].

PMID- 15258521
TI  - [Dermatitis and skin injuries from aquatic animals and flora].

PMID- 15258522
TI  - [Sturge-Weber-Krabbe syndrome (or encephalo-trigeminal angiomatosis)].

PMID- 15258523
TI  - [Psoriasis].

PMID- 15258524
TI  - [Epithelial antimicrobial peptides: local innate defense effector molecules].

PMID- 15258525
TI  - [Mutations in the gene coding for the extra-cellular 1 matricial protein in
      lipoid proteinosis].

PMID- 15258526
TI  - [Birt-Hogg-Dube syndrome and kidney neoplasia].

PMID- 15258527
TI  - [Plaques of trichoblastoma].

PMID- 15258528
TI  - [Side effects of interferon alpha2a and b].

PMID- 15258530
TI  - Intracytoplasmic sperm injection. Accomplishments and qualms.
AB  - AIM: Intracytoplasmic sperm injection (ICSI) is now the preferred technique for
      treatment of male factor infertility and many children have been born worldwide.
      However, concerns about the risk of transmitting genetic defects and development
      of ICSI children have been raised. We report clinical outcome of ICSI in Cornell
      University and results of screening for genetic defects in ICSI parents and their
      children. METHODS: Pregnancy and obstetrical outcomes as well as congenital
      malformations were analyzed. Chromosomal karyotyping and Yq deletion assessments
      were performed on blood samples. In addition, medical and developmental outcome
      were assessed in 3 and 5 year old ICSI children. RESULTS: We have performed 8 575
      ICSI cycles with ejaculated spermatozoa that resulted in a 75.4% fertilization
      and a 42.8% clinical pregnancy rates while for surgically retrieved specimen
      resulted in 66%, 48.8% respectively. The incidence of Y deletion was within the
      expected range for an infertile population, with identical deletions transmitted
      to the male offspring. There were no differences in cognitive, motor and
      behavioral development observed between ICSI children and these conceived
      naturally. CONCLUSION: The large majority of infertile men were treatable by
      ICSI, which resulted in the transmission of a specific abnormality but did not
      enhance the incidence of de novo deletions. There is no indication that ICSI
      children develop more congenital defects or express a lower psychomotor
      development that children conceived naturally. Nonetheless, genetic screening and
      counseling of couples undergoing ICSI would seem to be appropriate.

PMID- 15258531
TI  - Preimplantation diagnosis for aneuploidies in assisted reproduction.
AB  - At least one half of oocytes and preimplantation embryos are aneuploid and have
      to be avoided from transfer in in vitro fertilization (IVF) patients of advanced
      reproductive age. This can now be done by preimplantation genetic diagnosis,
      which has recently become an integral part of assisted reproduction technologies
      and was shown to improve implantation rate and reduce spontaneous abortions after
      implantation. The experience of approximately 5000 preimplantation genetic
      diagnosis (PGD) cycles performed for poor prognosis IVF patients have already
      resulted in birth of approximately 1000 apparently healthy children, suggesting
      that this novel technique is safe and reliable, and may in future replace the
      current IVF practice of preselection of embryos for transfer based on
      morphological parameters.

PMID- 15258532
TI  - The use of cryopreserved mature and immature spermatozoa in assisted
      reproduction.
AB  - Treatment of severe male subfertility has become available since the
      intracytoplasmic injection of a single sperm into an oocyte was successfully
      applied for the first time in 1992. Moreover, with the use of fresh and
      cryopreserved epididymal and testicular spermatozoa for this procedure,
      fertilization and pregnancies could be accomplished. This review addresses the
      development and performance of these techniques and discusses achievements and
      problems as well as future aspects of the feasibility of early spermatid
      injection. Furthermore, limitations of these procedures and concerns with regard
      to genetic and epigenetic risks of using immature gametes are discussed.

PMID- 15258533
TI  - Surgical sperm retrieval for assisted reproduction.
AB  - Intra-cytoplasmic sperm injection (ICSI) has revolutionized the treatment of male
      infertility by requiring only a single sperm to allow men whose infertility was
      previously considered to be uncorrectable to father a biological offspring. As a
      result, surgical sperm retrieval for assisted reproduction has developed to
      support this therapy. Microsurgical techniques have been applied to either
      identify areas of active spermatogenesis within the testis or to aspirate sperm
      containing fluid or tissue. The combination of these techniques with in vitro
      fertilization (IVF)/ICSI has been shown to be a powerful approach to the
      treatment of azoospermic men. The availability of sperm cryopreservation offers
      an additional advantage, negating the need for synchronization of sperm retrieval
      and ovulation. Thus, the advanced methods for sperm retrieval discussed in this
      review also provide therapeutic options, as compared the traditional diagnostic
      testicular biopsy.

PMID- 15258534
TI  - Assisted hatching.
AB  - Assisted hatching entails the opening or thinning of the zona pellucida before
      embryo transfer in order to improve the results of in vitro fertilization (IVF)
      and intracytoplasmic sperm injection (ICSI). The technique can be performed
      mechanically, chemically or with a laser beam. A piezoelectric method has also
      been described. Meta-analyses of randomised trials have shown that assisted
      hatching increases the clinical pregnancy, implantation and on-going pregnancy
      rates in patients with poor prognosis for IVF and ICSI, particularly those with
      repeated implantation failure. The technique is not without risks, and has been
      associated with an increased incidence of monozygotic twinning. Nevertheless, it
      remains an invaluable tool in assisted reproductive technology.

PMID- 15258535
TI  - The effect of sperm DNA damage on assisted reproduction outcomes. A review.
AB  - The quality of sperm DNA is very important in maintaining the reproductive
      potential of men. Sperm DNA is resistant to many types of insults that occur
      during its journey from the testis to time it reaches the oocyte for
      fertilization. During natural conception, a selection process occurs that allows
      only sperm with intact DNA to fertilize an oocyte. When assisted reproductive
      techniques (ART) are used, some or all of this selection process is bypassed. As
      a result, sperm with damaged DNA may fertilize an oocyte. Damage to sperm nuclear
      DNA negatively affects assisted and natural fertility. Increasingly, sperm DNA is
      being recognized as an independent measure of sperm quality that may have better
      diagnostic and prognostic capabilities than standard sperm parameters. This
      review summarizes the available evidence for the role of sperm DNA damage in
      assisted fertility. Two important facts are obvious from the available evidence:
      1) men with spermatozoal DNA damage appears to have a decreased ability to father
      offspring, 2) spermatozoa with abnormal DNA can fertilize an oocyte, which may
      progress to a live birth. Infertile men who are planning to undergo ART
      procedures with their partner should have their sperm evaluated for DNA damage.
      The results of this evaluation may be used to counsel the couple about their
      chances for live birth and for genomic abnormalities in their offspring.

PMID- 15258536
TI  - Mental development of children conceived using intracytoplasmic sperm injection.
      The current evidence.
AB  - There are biologically plausible reasons why children conceived using
      intracytoplasmic sperm injection (ICSI) may be at increased risk for delayed
      mental development. The first controlled study of mental development in ICSI
      children which was published in 1998 found 1 year old ICSI children to be at
      significantly increased risk for developmental delay compared with both in vitro
      fertilization (IVF) and naturally conceived control children. These results
      encouraged several groups of investigators to further study developmental
      outcomes for ICSI children in order to clarify the level of risk, if any. This
      review considers the currently available evidence from published studies which
      included control groups and a standardized measure of infant or child
      development. The 9 publications included in the review include a total of 969
      ICSI children and 828 controls (343 IVF, 485 naturally conceived). All studies
      indicate that the majority of children conceived using ICSI have normal mental
      development, and most have not found ICSI children to be at increased risk for
      developmental delay. The evidence to date suggests that ICSI per se is not an
      independent risk factor for delayed child development, but that demographic
      factors such as level of maternal education and social class are more important
      determinants of developmental outcome for ICSI children.

PMID- 15258537
TI  - [Etiopathogenesis of endometriosis related infertility].
AB  - In the last years the entire scientific community has devoted remarkable
      resources to the understanding of endometriosis. In spite of this, endometriosis
      remains one of the most complex gynecological diseases, in nearly all of its
      physiopathological aspects and implications. In particular, the association
      between endometriosis and infertility has proven to be complex and it has been
      widely discussed. It is generally accepted that moderate/severe endometriosis
      related sterility is due to mechanical factors, namely to the
      distortion/subversion of the regular pelvic anatomy. On the contrary, the factors
      behind infertility/subfertility related to minimal/mild endometriosis are less
      clear. None of the hypothesized mechanisms exhaustively explained the infertility
      related to endometriosis, while it is possible that such disease is caused by
      multiple factors altogether. The aim of this thorough review of the international
      literature is to analyze the main etiological factors (i.e. alterations in oocyte
      maturation and/or growth, defects of fertilization, impairments of implantation
      or aberrant immunological mechanisms) that are potentially involved, as well as
      the role that each of the above mentioned factors has in determining the
      endometriosis related infertility/subinfertility.

PMID- 15258538
TI  - [The meaning of fertility control in an integrated world].
AB  - Modern contraception was born out of the momentum of the demographic explosion
      that characterised the 20th century; today the phenomenon has acquired complexity
      because it is interconnected with population aging which is already very evident
      in the industrialised West, but is about to explode in the developing world too.
      Modern contraception played a decisive role in slowing down demographic growth
      which is now at a point below replacement level in numerous industrialised
      countries, including Italy. A phenomenon that has, unfortunately, often
      accompanied family planning education campaigns has been that of coercion: in the
      most highly populated countries and thus in those countries most exposed to the
      severe consequences of ultra-rapid increases in the population, governments and
      particularly zealous public servants have often resorted to more or less forced
      sterilisation and even abortion in order to achieve their targets. All of this
      ended in 1994 when the Cairo International Conference for Cooperation and
      Development recognised and sanctioned the new integrated concept of Reproductive
      Health. This new concept mandates that family planning and modern contraception
      must be integrated with all other interventions aimed at creating a state of
      psychophysical wellbeing in everything that concerns reproduction. Today then it
      is absolutely impossible to speak of "family planning", "fertility control" or
      "contraception" in isolated fashion; it is necessary to insert interventions in
      these fields into the global context of all other interventions in matters of
      reproduction. Finally, it should be recalled that in the 2nd half of the 20th
      century, after hundreds of thousands of years, homo sapiens performed at least 2
      revolutions: the contraceptive revolution, which permitted sexuality without
      reproduction, and the reproductive revolution, which permitted reproduction
      without sexuality. Given the speed of these changes it should not surprise that
      they were received with suspicion, not to say fear or panic. Progress should,
      however, be welcomed favourably provided it does not change the essence of the
      relationship between parents and children and the biological balance that
      sustains them.

PMID- 15258539
TI  - [Role of Doppler velocimetry of uterine arteries and ambulatory blood pressure
      monitoring in detecting pregnancies at risk for preeclampsia].
AB  - AIM: The aim of this study is to evaluate the performance of ambulatory blood
      pressure monitoring (ABPM) in association with Doppler velocimetry of uterine
      arteries in the detection of preeclampsia (PE). METHODS: In a prospective study,
      22 patients at risk for the development of PE have been en-rolled: 17 were
      nulliparous women with increased resistances in uterine arteries at 24 weeks and
      5 had an obstetric history of PE. All patients were tested with ABPM and uterine
      arteries Doppler velocimetry. A resistance index (RI) higher than 0.62 for the
      Doppler velocimetry and a diastolic midline estimating statistic of rhythm
      (MESOR) higher than 68 for the ABPM were considered abnormal. Patients were
      followed longitudinally until delivery. The occurrence of PE and low birth weight
      were considered as gestational outcomes endpoints. RESULTS: Overall, the mean
      gestational age at delivery was 36.3+/-3.4 weeks (range 29.4-41). Six out of 22
      (27.2%) patients developed PE; 4 out of 22 (18%) newborns were small for
      gestational age (SGA) <5 degrees percentile. In the prediction of PE, ABPM in
      association with Doppler velocimetry showed a positive predictive value (PPV) of
      42% and a negative predictive value (NPV) of 90%, for the development of low
      birth weight the PPV was 33% and the NPV 100%. CONCLUSION: This study shows that
      ABPM in association with Doppler velocimetry evaluation is a useful test to
      detect patients at high risk for the development of PE.

PMID- 15258540
TI  - [Effects of hormonal replacement therapy on breast density in postmenopausal
      women].
AB  - AIM: Recent studies have indicated that conventional hormonal replacement therapy
      (HRT) is associated with an increase in breast density. The aim of this non
      randomised prospective study was to evaluate the effects of HRT and Tibolone on
      breast density in postmenopausal women. METHODS: The study population included 41
      healthy women, who were on different HRT regimens and completed their 5-year
      mammographic follow-up. Before starting HRT, a baseline mammography was performed
      and repeated at 12-month interval during the follow-up. The patients, 41 healthy
      postmenopausal women, received 2 different treatments: continuous transdermal
      estrogen 50 microg/day plus sequential MPA 10 mg/day for 12 days at cycle (21
      patients), Tibolone 2.5 mg/day (20 patients). RESULTS: An increase in breast
      density was present in 25% of women receiving estrogen plus MPA. There was no
      mammographic breast density increase in Tibolone group; 9.5% of women receiving
      Tibolone showed reduced breast density. The modifications of breast density were
      reported during the 1st year of therapy. CONCLUSION: These findings show that
      different HRT regimens have different effects on breast density. Tibolone does
      not significantly affect breast density, so it may be a preferable therapy for a
      larger group of postmenopausal women, including those with a familiar history of
      breast cancer and those with breast density.

PMID- 15258541
TI  - [Thrombophilic syndrome associated to phenotypic resistance to activated protein
      C in postmenopausal women].
AB  - AIM: Hormone replacement therapy (HRT) may reduce the risk of cardiovascular
      events in healthy postmenopausal women. However recent studies suggest a 2-4 fold
      increased risk of idiopathic venous thromboembolism (VTE) among users of HRT. Our
      aim was to evaluate the overall effect of HRT on hemostatic variables probably
      related to increased VTE risk reported in epidemiological studies. METHODS:
      Therefore, 100 healthy postmenopausal women aged 45-60 years divided into 50 HRT
      non-users and 50 HRT users were examined. The authors assayed on the automated
      coagulometer ACL7000 (Instrumentation Laboratory, Milan) the procoagulant
      proteins: factor VIII (VIII:C) and factor VII (VII:C); the natural anticoagulant
      proteins: antithrombin (ATIII), protein C (PC), protein S (PS) and the resistance
      to anticoagulant action of activated protein C (APC-Resistance). The free tissue
      factor pathway inhibitor (TFPI) was measured with an ELISA method (Diagnostica
      Stago; France, Roche). The in vivo coagulation and fibrinolysis activation was
      evaluated by the assays of prothrombin fragment 1+2 (F1+2) and plasmin-
      antiplasmin complexes (PAP) using ELISA techniques. RESULTS: Increased levels of
      FVIII:C and FVII:C were observed in HRT users and HRT non-users women compared to
      controls (FVIII:C= 126+/-58%, 120+/-59% vs 85+/-15% p=0.0001; FVII: C 113+/-23%,
      103+/-19% vs 90+/-16% p=0.0001). The activation peptides were significantly
      different compared to those found in control subjects; higher values were
      observed in HRT users compared to HRT non-users (F1+2=1.11+/-0.44 nM, 077+/-0.31
      nM vs 0.45+/-0.35 p=0.00001; P-AP= 606+/-406 ng/ml, 514+/-205 ng/ml vs 235+/-59
      p=0.0001). The ATIII and the PC were similar among the 3 different groups of
      subjects, but reduced levels of PS were observed in HRT users (PS 93+/-23%, 105+/
      22% vs 109+/-12 p=0.0001). The mean normalized APC sensitivity ratio (APC-SR) was
      lower in the two populations of women as compared with that of controls (nAPC-SR
      1.02+/-0.7, 1.02+/-0.8 vs 1.1+/-25 p=0.02). The values of free TFPI were reduced
      in HRT users compared to HRT non-users (9.1+/-1.9 ng/ml, 10.1+/-2.3 ng/ml vs
      4.6+/-1.5 ng/ml p<0.0001). CONCLUSION: HRT appears to be associated to a shift in
      the procoagulant-anticoagulant balance towards a procoagulant state. The changes
      in hemostatic system could explain the increased risk of VTE in healthy
      postmenopausal women during HRT, nevertheless this risk could be higher in women
      known to have a congenital or acquired thrombophilic state.

PMID- 15258542
TI  - The incidence of chromosomal anomalies in fetuses affected by mild renal
      pyelectasis.
AB  - AIM: The aim of this study was to evaluate the clinical significance of
      borderline fetal pyelectasis, whether it is associated with chromosomal
      aberration or is the expression of a structural defect of the urinary tracts.
      METHODS: We carried out echographies on 2900 pregnant women in the 2nd trimester
      of their pregnancies between January 1998 and March 2002 at the Department of
      Obstetrics, Gynaecology and Neonatology. Any patient with fetuses affected by
      borderline pyelectasis in association with other echographic markers of
      aneuploidy and in women 35 years of age and older with fetuses presenting
      isolated pyelectasis underwent amniocentesis for karyotyping. RESULTS: We
      discovered 2.1% (62 cases) of borderline pyelectasis in the general population.
      The karyotype was normal in all cases of isolated pyelectasis; 3/5 of the fetuses
      with borderline renal pyelectasts associated with other risk factors showed a
      chromosomal aberration. CONCLUSION: In accordance with existing documentation,
      the results of our research confirmed that isolated borderline pyelectasis does
      not increase the risk of chromosomopathies; this latter is significantly more
      frequent when pyelectasis is present in older pregnant women (>35 years of age)
      or is associated with other sonographic markers of chromosomal anomalies
      (choroids plexus cysts, cystic hygroma etc.). Prenatal cytogenetic tests of the
      fetal karyotype are to be recommended in older mothers and/or in presence of
      associated echographic anomalies. In this study we propose an early diagnosis of
      mild forms of pyelectasis which are misdiagnosed by superficial echographies, but
      which can be associated with chromosomopathy.

PMID- 15258543
TI  - Sexually transmitted diseases and pelvic inflammatory disease.
AB  - AIM: The aim of this study was to determine the prevalence in the Turin area of
      the pathogens most implicated in pelvic inflammatory disease (PID), with
      particular regard to which risk factors the population taken into consideration
      is exposed to. METHODS: From January 1st 1997 to December 31(st) 2001, 13809
      women, aged between 14-54, all subjects being fertile and sexually active, were
      examined for the first time at St. Anna Hospital in Turin for the diagnosis of
      sexually transmitted diseases (STDs). A total of 5559 unselected patients were
      divided into 2 groups according to the presence (1721) or absence (3838) of
      subjective symptoms related to PID. Both groups underwent a cervico-vaginal
      bacteriological test for common pathogens, Candida spp., T. vaginalis, bacterial
      vaginosis, C. trachomatis, Mycoplasma spp., N. gonorrhoeae. The prevalence of
      each micro-organism was coupled with the anamnestic data collected from a pre
      determined questionnaire submitted to all patients. The questionnaire collected
      personal data: age at the time of first sexual intercourse; the number of
      partners in the last 6 months; the type of contraceptives used. Statistical
      analysis was performed using a chi squared test. RESULTS: In our analysis 2
      factors proved to be decisive for a correct PID diagnosis: a subjective
      symptomatology and an anamnesis mainly focused on risk factor evaluation. This
      result is in accordance with what has been emphasized many times in the
      literature, i.e. many of these infections have only a few or no symptoms at all.
      CONCLUSION: Greater attention to the anamnestic data collection would therefore
      be the key to focusing the clinical investigations on those who are at a major
      risk to contracting STDs.

PMID- 15258544
TI  - [Preliminary results of the Italian epidemiological study on vulvo-vaginitis].
AB  - AIM: The aim of this work was to evaluate the prevalence of symptomatic vulvo
      vaginal infections among the Italian female population and the diagnostic
      approach of 158 Italian gynaecologists. METHODS: A total of 1644 patients were
      enrolled in this survey. A presumed diagnosis of vulvovaginal infection was made
      according to specific clinical and laboratory criteria (pH e sniff test) in 902
      (55.4%) cases, whereas a definitive diagnosis was made in 1439 (87.5%) cases. The
      definitive diagnoses were as follows: 844 (51.3%) vulvovaginal mycosis, 327
      (19.9%) bacterial vaginosis, 110 (6.7%) trichomonal infection, 100 (6.1%)
      aspecific bacterial vaginitis, 58 (3.5%) non-infectious vaginitis. As assessed by
      typing, mycosis were mainly due to Candida albicans infections in 459 cases
      (78%). CONCLUSION: From the survey it is possible to infer that: 1) only thanks
      to the employed microbiological diagnostic tests a definitive diagnosis was made
      in 702 patients without a previous presumed diagnosis; 2) mycotic infections were
      underestimated; 3) Candida albicans was the most common species causing female
      low genital tract mycotic infections. In conclusion, these data underline the
      importance of laboratory examinations in the diagnosis of low genital tract
      infections for the ambulatory gynaecological practice.

PMID- 15258545
TI  - Haemoglobin E in pregnancy. A case report. Diagnosis, familiar study and
      counselling, follow up until delivery and new-born observation.
AB  - Haemoglobin E is a beta chain variant quite common in Southeastern Asia. The case
      of a gravid Thai woman with a microcytic anaemia is reported. The diagnosis of
      homozygous haemoglobin E was suspected on the basis of ethnic considerations when
      analysis of her haemoglobin showed the absence of normal HbA1 and about 100% of a
      variant Hb with electrophoretic mobility with HbC and HbA2. Identification of the
      haemoglobin variant was performed by using an association of alkaline
      electrophoresis on agarose gel, acid electrophoresis on agarose gel, haemoglobin
      isoelectrofocusing, high performance liquid chromatography. A study of
      haemoglobin pattern in the partner, parents and siblings was also performed.
      Pregnancy continued without any problems until the 40th week when a caesarean
      section was performed due to a difficult labour with foetal distress. The
      haemoglobin pattern of the new-born was studied at birth and after 1 year; as
      expected, it was quite normal at birth and a heterozygous condition for HbE was
      observed after 1 year. HbE, in even heterozygous and homozygous states, gives a
      mild clinical picture but its association with other haemoglobinopathies, such as
      a double heterozygous state (i.e. HbE/beta Thalassaemia) gives rise to a severe
      transfusion dependent thalassaemia syndrome. It is the authors' opinion that only
      a strict interaction between obstetricians and pathologists is the possible
      correct answer to the new diagnostic question proposed by a rapidly evolving
      inter-ethnic society.

PMID- 15258546
TI  - [Ultrasonographic evaluation of timing in emergency cervical cerclage].
AB  - The aim of the present paper is to utilise endovaginal ultrasonography as an
      instrument for establishing the most appropriate moment for carrying out cervical
      cerclage after interrupting uterine contractions in a situation of near
      miscarriage. A patient at 20 weeks and 4 days of gestation, with contractions,
      integral membranes and complete dilatation, was laid in the Trendelemburg
      position, keeping the bladder moderately full, and given tocolytic therapy. After
      14 days cerclage was carried out on a reconstituted neck. At 37 weeks and 1 day,
      the patient delivered a female newborn weighing 3.100 g. The Trendelemburg
      position, the moderately full bladder and tocolytic therapy with endovaginal
      ultrasonographic monitoring can move the timing of surgery forward so as to
      render it safer and more useful for prognostic purposes.

PMID- 15258547
TI  - [Outcome of pregnancy in patient with cloacal dysgenesis].
AB  - The cloacal dysgenesis or persistent cloaca is an anomaly included in urogenital
      tract malformations (UGM) and, in particular, in anomalies due to a missed
      development of the urogenital septum. The UGM occur during 6-11th weeks of
      gestation owing to a stop and/or alteration of the normal development and
      subdivision process of the cloaca, the embryonic structure from which gives
      origin to the ano-rectal segment of midgut, bladder, ureters, vagina and uterus.
      The case of a patient submitted to many surgical treatments for urogenital tract
      congenital malformations is described; when pregnant, she carried other pregnancy
      until the 34th week of gestation, giving birth a newborn by cesarean section. The
      patient was checked constantly for her general conditions and, in particular, her
      renal functions by an active collaboration between internist, nephrologist and
      gynecologist.

PMID- 15258548
TI  - [Prevention and treatment of congenital toxoplasmosis: organization protocol].
AB  - AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of
      debate among obstetricians, pediatricians and epidemiologists. There is no
      consensus about antenatal screening and diagnostic tests, nor there is about
      treatment for presumed infection in pregnancy. As an example of this type of
      organisation for health care delivery, a regional model has been promoted as a
      multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis.
      The model had been designed on the national guidelines of the National Health
      Institute (Istituto Superiore di Sanita, ISS). METHODS: Suspected maternal
      infections are referred and seen as outpatients at our centre on a specific day
      of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity
      titres) are performed at the Institute of Virology of the University of Bari, and
      patients are started on spiramycin. All cases of true or presumed seroconversion
      are counselled for amniotic fluid sampling and the sample is sent to ISS. In
      cases of late seroconversion and positive amniotic fluid results, patients are
      prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until
      the end of pregnancy. A fetal-neonatal follow-up is performed in all cases.
      RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis
      infection have been referred (average 60 cases per year). We have been able to
      reclute, since the adoption of the national network protocol, 1/3 of presumed
      regional cases with a positive increasing trend. CONCLUSION: The service for
      prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from
      the adoption of this protocol, which combines adherence to a national network and
      pays respect to regional requirements.

PMID- 15258549
TI  - Nuchal translucency as an important ultrasound screening tool for the early
      diagnosis of first trimester chromosomal abnormalities. A preliminary experience.

PMID- 15258550
TI  - [Intractable post-partum hemorrhage].

PMID- 15258551
TI  - [Herpes simplex virus and working women].

PMID- 15258552
TI  - [Bone density and mineral metabolism in calcitonin-deficiency patients].
AB  - AIM: Calcitonin is a hormone secreted by thyroid C-cells. Its primary effect
      seems to be a direct inhibition of bone degradation, but the physiological
      function of calcitonin in humans is still uncertain. The role of this hormone in
      the development of osteoporosis is unknown, but few authors have shown bone mass
      reduction in thyroidectomy patients. METHODS: To investigate the influence of
      calcitonin deficiency on bone turnover, 9 males (age 31 to 66 years) submitted to
      total thyroidectomy in 1996 for non-toxic goitre have been studied. These
      patients received thyroxine treatment at individual dose but never with
      suppressed TSH levels. Moreover 8 sex-, age- and Body Mass Index-matched normal
      subjects have also been studied as control group. RESULTS: Calcitonin was
      undetectable in thyroidectomized patients, while the mean value was 7.1+/-3.2
      pg/ml in the control group. At bone ultrasonography 50% of patients showed
      osteopenia, while only 1 subject showed osteopenia in the control group. The mean
      calcium serum level of patients was significant lower than in the control group
      (p<0.001). Calcium urinary level was increased in patients than controls. PTH
      serum levels were statistically decreased (p<0.001) in patients more than in
      controls. Osteocalcin showed a significantly (p<0.05) lower bone formation in
      patients than in controls, while the markers of resorption, deoxypyridinoline and
      N-terminal telopeptide of type I collagen, suggested an increased bone turnover
      in calcitonin-deficiency patients. CONCLUSION: The results of this study show
      that the chronic lack of calcitonin in total thyroidectomized patients may play a
      role in increased bone degradation and osteopenia with a higher risk of bone
      fracture.

PMID- 15258553
TI  - Pioglitazone reduces blood pressure in non-dipping diabetic patients.
AB  - AIM: The association between insulin resistance and hypertension is firmly
      established and has been extensively investigated. Thiazolidinediones (TZD), a
      class of oral hypoglycemic agents that act as insulin sensitizers have been
      demonstrated, in many in vivo and in vitro studies, to possess antihypertensive
      properties. Whether the ability of TZD to lower blood pressure (BP) should be
      ascribed to a reduction of insulin resistance, or to a direct vasodilating
      effect, is matter of debate. Since blunted BP nocturnal dipping precedes overt
      hypertension and is associated with an increased risk of adverse cardiovascular
      events, we evaluated the pioglitazone effects on BP in non-dipper type 2 diabetic
      patients. METHODS: Forty non-dipper diabetic patients were randomly assigned to
      metformin + placebo (M) or metformin + pioglitazone 30 mg (MP) and submitted to
      24 hours blood pressure monitoring at the beginning and after 8 weeks. RESULTS:
      After 8 weeks of treatment in subjects on metformin + pioglitazone 30 mg (group
      MP1), we found a reduction of nocturnal blood pressure values (mean nocturnal
      systolic BP 128.05+/- 1.23 vs 122.8+/-2.3 mmHg; p<0.02; mean nocturnal diastolic
      BP 81.2+/-0.99 vs 75.65+/-0.93 mmHg; p<0.005). The observed improvements in BP
      were independent from changes in metabolic parameters. CONCLUSION: The obtained
      data show that pioglitazone was effective in reducing BP values in non-dipping
      diabetic patients. The reduction of BP values was independent from amelioration
      of the metabolic picture: that suggest the hypothesis that these ameliorations
      may be also due to a direct antihypertensive action exerted by pioglitazone.

PMID- 15258554
TI  - Von Recklinghausen's neurofibromatosis associated with duodenal somatostatinoma.
      A case report and review of the literature.
AB  - Somatostatin producing duodenal carcinoids are rare, comprising a mere 2% of
      small bowel carcinoids and 5-10% of all duodenal tumors. Since the 1st case
      described by Kaneko in 1979 more than 50 cases have been reported in the world
      literature. From these reports, it is gradually emerging that duodenal
      somatostatinomas may show a strong association with von Recklinhausen's
      neurofibromatosis (VRNF) as a distinct neuroendocrine syndrome. A case of a
      patient affected by VRNF associated with duodenal somatostatinoma with consequent
      obstructive jaundice is reported. The authors discuss the characteristics of
      these tumors and review the literature. A total of 27 patients with Von
      Recklinghausen's disease associated with immunohistologically proved duodenal
      somatostatinoma have been identified and compared with 29 duodenal
      somatostatinoma not associated with VRNF, and with 32 cases of pancreatic
      somatostatinomas.

PMID- 15258555
TI  - [Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a
      case report].
AB  - The case of a 62-year-old woman with severe post-menopausal hirsutism is
      described. Her clinical history revealed regular menstrual periods until
      menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non
      insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism,
      which had developed in the previous 3 years, with a deeping of the voice.
      Examination showed android obesity, hypertension and severe hirsutism involving
      the face and the trunk. Endocrine evaluation pointed out regular adrenal
      function, serum total and free-testosterone in the adult male range, with normal
      androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH
      and FSH were inappropriately low for her post-menopausal age. Computed tomography
      of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol
      scan was negative. A further pelvic transvaginal ultrasonography revealed a small
      cystic formation near the right ovary and a slight increase in the size of the
      left ovary. The patient underwent bilateral ovariectomy. Histological examination
      showed a lipoid cell tumor within the left ovary. Immunohistochemical studies
      were positive for inhibin and cytokeratin. After surgery, serum testosterone fell
      to normal levels, gonadotropins increased to menopausal levels, confirming that
      the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism
      greatly improved. Periodic hormonal tests remained normal and CT of the abdomen
      and pelvic ultrasonography did not show alterations at a 3 years follow-up.

PMID- 15258556
TI  - High-sensitivity C-reactive protein: clinical importance.
AB  - High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that
      predicts incident myocardial infarction, stroke, peripheral arterial disease, and
      sudden cardiac death among healthy individuals with no history of cardiovascular
      disease, and recurrent events and death in patients with acute or stable coronary
      syndromes. hsCRP confers additional prognostic value at all levels of
      cholesterol, Framingham coronary risk score, severity of the metabolic syndrome,
      and blood pressure, and in those with and without subclinical atherosclerosis.
      hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L are associated with
      lower, moderate, and higher cardiovascular risks, respectively. This article
      summarizes epidemiologic data on the relation between CRP and atherothrombotic
      disease and provides clinical guidelines for hsCRP screening in cardiovascular
      risk assessment.

PMID- 15258557
TI  - Telomere length predicts neutrophil recovery in the absence of G-CSF after
      autologous peripheral blood stem cell transplantation.
AB  - SUMMARY: Haemopoietic regeneration after autologous peripheral blood progenitor
      cell (PBPC) transplantation can be delayed in some patients despite adequate
      infusion of CD34(+) cells. This suggests variability in the proliferation
      potential of the implanted cells, a capacity that may be predicted by their
      telomere length. To test this theory, telomere length was measured on stored
      apheresis samples from 36 patients aged 46.6+/-11.1 years, who had undergone
      successful autologous PBPC transplantation with a median of 5.6 x 10(6)/kg (1.3 x
      10(6)-36.1 x 10(6)/kg) CD34(+) cells. The mean PBPC telomere length for the
      cohort was 9.4+/-2.3 kbp. For patients who did not receive G-CSF post
      transplantation (n=7), days to absolute neutrophil recovery (ANC), >/=0.1, 0.5
      and 1.0 x 10(9) cells/l, were significantly inversely correlated with telomere
      length of the infused PBPC (r=-0.88, -0.81, -0.77, respectively; P<0.05,).
      However, no correlation was found for patients who received G-CSF from day 1 post
      transplantation (n=20). These data suggest that for transplantation with
      sufficient CD34(+) cells, neutrophil recovery is less efficient in patients
      receiving infusions of cells with short telomeres, but this deficiency can be
      corrected with adequate post transplantation administration of G-CSF. Bone Marrow
      Transplantation (2004) 34, 439-445. doi:10.1038/sj.bmt.1704607 Published online
      19 July 2004

PMID- 15258558
TI  - Clinical outcomes of patients with impaired left ventricular ejection fraction
      undergoing autologous bone marrow transplantation: can we safely transplant
      patients with impaired ejection fraction?
AB  - Experience with autologous bone marrow transplantation (ABMT) in patients with
      impaired left ventricular ejection fraction (LVEF) or heart failure (HF) is
      limited. We identified 308 consecutive patients who underwent ABMT for Hodgkin's
      or non-Hodgkin's lymphoma at our institution (1996-2003). Patient
      characteristics, clinical course and overall survival were compared between
      patients with preserved ( > or = 50%) or impaired ( < 50%) LVEF. Of the 308
      patients identified, 20 had baseline impaired LVEF (four with LVEF < or = 40%,
      all NYHA class I-II HF). None of the patients with post-ABMT echocardiogram had
      worsened LVEF (n = 7). Among the 20 patients with impaired LVEF, four patients
      had reversible cardiac complications post-ABMT (including worsening HF). The two
      deaths observed in the impaired LVEF group were both due to noncardiac causes.
      The 5-year survival was similar between patients with preserved and impaired LVEF
      (P = 0.43). Careful selection of patients with stable, mild-to-moderate HF and
      impaired LVEF for ABMT can achieve similar long-term survival. As medical care
      for HF and ABMT improves, the exclusion criteria for ABMT with regard to HF and
      impaired LVEF should be re-examined.

PMID- 15258559
TI  - Continuous infusion idarubicin and oral busulfan as conditioning for patients
      with acute myeloid leukemia aged over 60 years undergoing autologous stem cell
      transplantation.
AB  - There is growing interest in autologous stem cell transplantation (ASCT) for
      elderly patients with acute myeloid leukemia (AML). While mortality and toxicity
      from ASCT have been reduced, relapse rate is still high. In a prospective study,
      we investigated the feasibility of a new conditioning regimen consisting of high
      dose idarubicin plus busulfan in AML patients aged over 60 years undergoing ASCT.
      A total of 14 patients (median age: 64 years) received 2 days continuous infusion
      of idarubicin at 20 mg/m2/day, followed by 3 days of oral busulfan (4 mg/kg/day)
      as conditioning. No case of transplant-related mortality occurred. The median
      number of days to neutrophil ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l)
      recovery was 11 and 12, respectively. Cardiac toxicity was absent, while 12
      patients (86%) had grade 3-4 mucositis. After a median follow-up of 9 months from
      ASCT, nine of 14 patients are alive in continuous complete remission (CR), four
      have relapsed at 3, 6, 8 and 9 months, and one died in CR1 from gastric cancer.
      Our data demonstrate the feasibility of a conditioning regimen based on high-dose
      idarubicin plus busulfan in elderly AML patients. Results concerning reduction of
      relapse rate need confirmation in a larger series with longer follow-up.

PMID- 15258560
TI  - Severe multiorgan failure after parvovirus B19 infection in an allogeneic stem
      cell transplant recipient.

PMID- 15258561
TI  - Monitoring of minimal residual disease using WT1 assay for patients with chronic
      myeloid leukemia who undergo allogeneic stem cell transplantation.

PMID- 15258562
TI  - Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation:
      incidence, risk factors and outcomes.
AB  - Recent studies suggest that cancer patients may be at increased risk for
      supraventricular tachyarrhythmias (SVTA). We have observed clinically significant
      SVTA in patients undergoing hematopoietic stem cell transplantation occurring at
      a median of 6 days post transplant, manifesting as atrial fibrillation/flutter or
      regular narrow-complex tachycardia and persisting for a median of 3 days (range,
      0-8). All patients received aggressive medical therapy and/or electrical
      cardioversion to restore sinus rhythm and to re-establish hemodynamic stability.
      Non-Hodgkin's lymphoma (NHL) was the most common diagnosis (53%), and a case
      control analysis in those patients demonstrated that SVTA occurred in 12% of
      patients and was associated with older age and pre-existing cardiac conditions.
      In conclusion, patients undergoing HSCT are at moderate risk for developing SVTA,
      particularly older patients with a diagnosis of NHL. These arrhythmias are
      clinically significant, and are a marker for increased mortality and prolonged
      hospital stay. Additional studies are needed to identify high-risk patients who
      may benefit from prophylactic anti-arrhythmic therapy.

PMID- 15258563
TI  - Detection and expression of human BK virus sequences in neoplastic prostate
      tissues.
AB  - BK virus (BKV) is ubiquitous in the human population and establishes a lifelong,
      subclinical persistent infection in the urinary tract. When the immune system is
      compromised, it can cause severe disease in the kidney and bladder. Detection of
      BKV sequences in urinary tract neoplasms has led to the postulate that this virus
      may induce human oncogenesis through the function of its large tumor antigen
      (TAg). In this study, examination of prostate tumor tissue sections using in situ
      hybridization shows the presence of BKV sequences in atrophic epithelium.
      Solution polymerase chain reaction on DNA extracted from the tissues and sequence
      analysis of the products reveal the presence of BKV regulatory and early region
      sequences. In addition, immunohistochemical analysis using monoclonal antibodies
      specific to TAg or p53 shows the expression of TAg in some of the samples and p53
      staining that can be correlated to TAg expression. Although the normal cellular
      localization of TAg and p53 is nuclear, double immunofluorescence labeling with
      anti-p53 and TAg antibodies indicates colocalization of p53 and TAg to the
      cytoplasm in the glandular epithelial cells of the sections. Although BKV DNA was
      found in benign and atrophic lesions, TAg and p53 coexpression was observed only
      in atrophic lesions.

PMID- 15258564
TI  - Possible role of FLICE-like inhibitory protein (FLIP) in chemoresistant ovarian
      cancer cells in vitro.
AB  - Chemoresistance is a major therapeutic problem and the current knowledge on
      cellular mechanisms involved is incomplete. In the present study, we have
      investigated the possible involvement of Fas-associated death domain-like
      interleukin-1beta-converting enzyme (FLICE)-like inhibitory protein (FLIP) in
      ovarian cancer resistance by comparing chemosensitive (OV2008) and chemoresistant
      (C13*) ovarian cancer cells treated with cisplatin in vitro, and/or transfected
      with FLIP sense cDNA or FLIP small interfering RNA (siRNA) and determining FLIP
      protein content, cleavage of caspase-8 and caspase-3 and apoptosis. Cisplatin
      significantly decreased FLIP protein level, induced cleavage of caspase-8 and
      caspase-3 and apoptosis in a concentration-dependent manner in cisplatin
      sensitive but not -resistant cells. While overexpression of FLIP-attenuated
      cisplatin-induced cleavage of caspase-8 and caspase-3 and apoptosis in
      chemosensitive cells, downregulation of FLIP in chemoresistant cells by siRNA
      increased apoptosis induced by cisplatin. These results suggest that FLIP plays a
      significant role in the regulation of apoptosis in human ovarian cancer cells and
      their sensitivity to cisplatin. This cell survival factor may be an important
      determinant in chemoresistance in ovarian cancer and may serve as a molecular
      target for the development of novel therapy for chemoresistant ovarian cancer.

PMID- 15258565
TI  - XIAP and survivin as therapeutic targets for radiation sensitization in
      preclinical models of lung cancer.
AB  - Survivin and XIAP are members of inhibitors of apoptosis (IAPs) family. They are
      upregulated in various malignancies. Inactivation of these molecules has resulted
      in chemosensitization. The purpose of this study was to determine whether
      inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer
      model. Transient transfection of H460 cells with antisense oligonucleotides
      (ASOs) against either molecule has specifically reduced their expression, by
      Western analysis. Results from 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and clonogenic assays suggest that inhibition of survivin or
      XIAP greatly decreased cell survival following irradiation. A significantly
      increased number of apoptotic cells were detected when H460 cells were treated
      with either antisurvivin, anti-XIAP or both ASOs (P=0.03, 0.0003 and 0.01,
      respectively) plus irradiation. H460 xenografts that were treated with ASOs plus
      radiotherapy demonstrated growth delay beyond 15 days. Growth delay in the groups
      of combined treatment was greater than that in other groups. However, treatment
      with ASOs alone did not affect tumor growth delay in mice, but decreased the
      survival of H460 cells in culture. Antisense treatment did not cause any
      mortality or weight loss during the 32 days of study. These data suggest that
      inhibition of survivin or XIAP radiosensitizes H460 lung cancer cells by
      upregulating apoptosis and downregulating cell survival. Combination of
      radiotherapy and inhibition of survivin and XIAP through the antisense approach
      results in improved tumor control by radiotherapy in a mouse model of lung
      cancer.

PMID- 15258566
TI  - AKAP12/Gravin is inactivated by epigenetic mechanism in human gastric carcinoma
      and shows growth suppressor activity.
AB  - AKAP12/Gravin, one of the A-kinase anchoring proteins (AKAPs), functions as a
      kinase scaffold protein and as a dynamic regulator of the beta2-adrenergic
      receptor complex. However, the biological role of AKAP12 in cancer development is
      not well understood. The AKAP12 gene encodes two major isoforms of 305 and 287
      kDa (designated AKAP12A and AKAP12B, respectively, in this report). We found that
      these two isoforms are independently expressed and that they are probably under
      the control of two different promoters. Moreover, both isoforms were absent from
      the majority of human gastric cancer cells. The results from methylation-specific
      PCR (MSP) and bisulfite sequencing revealed that the 5' CpG islands of both
      AKAP12A and AKAP12B are frequently hypermethylated in gastric cancer cells.
      Treatment with DNA methyltransferase inhibitor and/or histone deacetylase
      inhibitor efficiently restored the expression of AKAP12 isoforms, confirming that
      DNA methylation is directly involved in the transcriptional silencing of AKAP12
      in gastric cancer cells. Hypermethylation of AKAP12A CpG island was also detected
      in 56% (10 of 18) of primary gastric tumors. The restoration of AKAP12A in AKAP12
      nonexpressing cells reduced colony formation and induced apoptotic cell death. In
      conclusion, our results suggest that AKAP12A may function as an important
      negative regulator of the survival pathway in human gastric cancer.

PMID- 15258567
TI  - ATM activity contributes to the tumor-suppressing functions of p14ARF.
AB  - P14/p19ARF (ARF) plays a major role in the activation of p53 by oncogenic
      signals. The biochemical basis of this has not been fully elucidated. We report
      here that forced expression of p14ARF enhances phosphorylation of p53 serine 15
      (p53S15) in NIH3T3, IMR90 and MCF7 cells. Ectopic expression of the oncogenes c
      myc, E2F1 and E1A, all of which activate p53 at least partially via ARF, lead to
      p53S15 phosphorylation in IMR90 cells. In addition, ectopic expression of p53
      also results in p53S15 phosphorylation, suggesting that this is a common event in
      the ARF-p53 tumor suppression system. Furthermore, p53-, p14ARF-, c-myc- and E2F1
      , but not E1A-, induced p53S15 phosphorylation was substantially reduced in AT
      fibroblasts (GM05823). Downregulation of ATM in MCF7 cells using RNA interference
      (RNAi) technology significantly attenuated p14ARF- and p53-induced
      phosphorylation of p53S15. Ectopically expressed ARF in NIH3T3 cells induced ATM
      nuclear foci and activated ATM kinase. Functionally, ectopic expression of p14ARF
      and c-myc inhibited the proliferation of IMR90 but not ATM null GM05823 cells,
      and p14ARF-induced inhibition of MCF7 cell proliferation was significantly
      attenuated by downregulation of ATM by RNAi. Taken together, these data show a
      functional role for ATM in ARF-mediated tumor suppression.

PMID- 15258568
TI  - Nucleosomes facilitate their own invasion.
AB  - DNA wrapped in nucleosomes is sterically occluded, creating obstacles for
      polymerase, regulatory, remodeling, repair and recombination complexes, which
      require access to the wrapped DNA. How such complexes recognize and gain access
      to their DNA target sites is not known. Here we report the direct detection of a
      dynamic equilibrium conformational transition in nucleosomes that greatly
      increases the distance between the end of the nucleosomal DNA and the histone
      core. We quantified the equilibrium constant for this transition under
      physiological conditions. As predicted by these findings, addition of LexA
      protein to nucleosomes containing the LexA target site drives this conformational
      equilibrium toward the unwrapped, accessible state, simultaneously allowing
      stable LexA binding. This inherent property of nucleosomes allows any protein,
      whether an energy-dependent machine or a passive binder, to gain access even to
      buried stretches of nucleosomal DNA.

PMID- 15258569
TI  - Identification, function and structure of the mycobacterial sulfotransferase that
      initiates sulfolipid-1 biosynthesis.
AB  - Sulfolipid-1 (SL-1) is an abundant sulfated glycolipid and potential virulence
      factor found in Mycobacterium tuberculosis. SL-1 consists of a trehalose-2
      sulfate (T2S) disaccharide elaborated with four lipids. We identified and
      characterized a conserved mycobacterial sulfotransferase, Stf0, which generates
      the T2S moiety of SL-1. Biochemical studies demonstrated that the enzyme requires
      unmodified trehalose as substrate and is sensitive to small structural
      perturbations of the disaccharide. Disruption of stf0 in Mycobacterium smegmatis
      and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively.
      The structure of Stf0 at a resolution of 2.6 A reveals the molecular basis of
      trehalose recognition and a unique dimer configuration that encloses the
      substrate into a bipartite active site. These data provide strong evidence that
      Stf0 carries out the first committed step in the biosynthesis of SL-1 and
      establish a system for probing the role of SL-1 in M. tuberculosis infection.

PMID- 15258570
TI  - Allosteric inhibition of protein tyrosine phosphatase 1B.
AB  - Obesity and type II diabetes are closely linked metabolic syndromes that afflict
      >100 million people worldwide. Although protein tyrosine phosphatase 1B (PTP1B)
      has emerged as a promising target for the treatment of both syndromes, the
      discovery of pharmaceutically acceptable inhibitors that bind at the active site
      remains a substantial challenge. Here we describe the discovery of an allosteric
      site in PTP1B. Crystal structures of PTP1B in complex with allosteric inhibitors
      reveal a novel site located approximately 20 A from the catalytic site. We show
      that allosteric inhibitors prevent formation of the active form of the enzyme by
      blocking mobility of the catalytic loop, thereby exploiting a general mechanism
      used by tyrosine phosphatases. Notably, these inhibitors exhibit selectivity for
      PTP1B and enhance insulin signaling in cells. Allosteric inhibition is a
      promising strategy for targeting PTP1B and constitutes a mechanism that may be
      applicable to other tyrosine phosphatases.

PMID- 15258571
TI  - Clostridium perfringens epsilon-toxin shows structural similarity to the pore
      forming toxin aerolysin.
AB  - Epsilon-toxin from Clostridium perfringens is a lethal toxin. Recent studies
      suggest that the toxin acts via an unusually potent pore-forming mechanism. Here
      we report the crystal structure of epsilon-toxin, which reveals structural
      similarity to aerolysin from Aeromonas hydrophila. Pore-forming toxins can change
      conformation between soluble and transmembrane states. By comparing the two
      toxins, we have identified regions important for this transformation.

PMID- 15258572
TI  - Structure-function defects of human mitochondrial DNA polymerase in autosomal
      dominant progressive external ophthalmoplegia.
AB  - Progressive external ophthalmoplegia (PEO) is a mitochondrial disorder associated
      with mutations in the POLG gene encoding the mitochondrial DNA polymerase (pol
      gamma). Four autosomal dominant mutations that cause PEO encode the amino acid
      substitutions G923D, R943H, Y955C and A957S in the polymerase domain of pol
      gamma. A homology model of the pol gamma catalytic domain in complex with DNA was
      developed to investigate the effects of these mutations. Two mutations causing
      the most severe disease phenotype, Y955C and R943H, change residues that directly
      interact with the incoming dNTP. Polymerase mutants exhibit 0.03-30% wild-type
      polymerase activity and a 2- to 35-fold decrease in nucleotide selectivity in
      vitro. The reduced selectivity and catalytic efficiency of the autosomal dominant
      PEO mutants predict in vivo dysfunction, and the extent of biochemical defects
      correlates with the clinical severity of the disease.

PMID- 15258573
TI  - Contact-damage-resistant ceramic/single-wall carbon nanotubes and
      ceramic/graphite composites.
AB  - There has been growing interest in incorporating single-wall carbon nanotubes
      (SWNTs) as toughening agents in brittle ceramics. Here we have prepared dense
      Al(2)O(3)/SWNT composites using the spark-plasma sintering (SPS) method. Vickers
      (sharp) and Hertzian (blunt) indentation tests reveal that these composites are
      highly contact-damage resistant, as shown by the lack of crack formation.
      However, direct toughness measurements, using the single-edge V-notch beam
      method, show that these composites are as brittle as dense Al(2)O(3) (having a
      toughness of 3.22 MPa m(0.5)). This type of unusual mechanical behaviour was also
      observed in SPS-processed, dense Al(2)O(3)/graphite composites. We argue that the
      highly shear-deformable SWNTs or graphite heterogeneities in the composites help
      redistribute the stress field under indentation, imparting the composites with
      contact-damage resistance. These composites may find use in engineering and
      biomedical applications where contact loading is important.

PMID- 15258574
TI  - Polymer-assisted deposition of metal-oxide films.
AB  - Metal oxides are emerging as important materials for their versatile properties
      such as high-temperature superconductivity, ferroelectricity, ferromagnetism,
      piezoelectricity and semiconductivity. Metal-oxide films are conventionally grown
      by physical and chemical vapour deposition. However, the high cost of necessary
      equipment and restriction of coatings on a relatively small area have limited
      their potential applications. Chemical-solution depositions such as sol-gel are
      more cost-effective, but many metal oxides cannot be deposited and the control of
      stoichiometry is not always possible owing to differences in chemical reactivity
      among the metals. Here we report a novel process to grow metal-oxide films in
      large areas at low cost using polymer-assisted deposition (PAD), where the
      polymer controls the viscosity and binds metal ions, resulting in a homogeneous
      distribution of metal precursors in the solution and the formation of uniform
      metal-organic films. The latter feature makes it possible to grow simple and
      complex crack-free epitaxial metal-oxides.

PMID- 15258575
TI  - Surface-mediated gene transfer from nanocomposites of controlled texture.
AB  - Safe and efficient gene delivery would have great potential in gene therapy and
      tissue engineering, but synthetic biomaterial surfaces endowed with efficient
      gene-transferring functions do not yet exist. Inspired by naturally occurring
      biomineralization processes, we co-precipitated DNA with inorganic minerals onto
      cell-culture surfaces. The DNA/mineral nanocomposite surfaces obtained not only
      supported cell growth but also provided high concentrations of DNA in the
      immediate microenvironment of the cultured cells. Gene transfer from the
      engineered surfaces was as efficient as an optimized commercial lipid
      transfection reagent; in addition, the extent of gene transfer was adjustable by
      varying the mineral composition. DNA/mineral nanocomposite surfaces represent a
      promising system for enhancing gene transfer and controlling the extent of gene
      transfer for various biomedical applications, including tissue engineering or
      gene therapy of bone.

PMID- 15258576
TI  - Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness.
AB  - Allergic asthma is a complex syndrome characterized by airway obstruction, airway
      inflammation and airway hyper-responsiveness (AHR). Using a mouse model of
      allergen-induced AHR, we previously demonstrated that CD8-deficient mice develop
      significantly lower AHR, eosinophilic inflammation and interleukin (IL)-13 levels
      in bronchoalveolar lavage fluid compared with wild-type mice. These responses
      were restored by adoptive transfer of antigen-primed CD8(+) T cells. Previously,
      two distinct populations of antigen-experienced CD8(+) T cells, termed effector
      (T(EFF)) and central memory (T(CM)) cells, have been described. After adoptive
      transfer into CD8-deficient mice, T(EFF), but not T(CM), cells restored AHR,
      eosinophilic inflammation and IL-13 levels. T(EFF), but not T(CM), cells
      accumulated in the lungs, and intracellular cytokine staining showed that the
      transferred T(EFF) cells were a source of IL-13. These data suggest an important
      role for effector CD8(+) T cells in the development of AHR and airway
      inflammation, which may be associated with their Tc2-type cytokine production and
      their capacity to migrate into the lung.

PMID- 15258577
TI  - P2X7 receptor inhibition improves recovery after spinal cord injury.
AB  - Secondary injury exacerbates the extent of spinal cord insults, yet the
      mechanistic basis of this phenomenon has largely been unexplored. Here we report
      that broad regions of the peritraumatic zone are characterized by a sustained
      process of pathologic, high ATP release. Spinal cord neurons expressed P2X7
      purine receptors (P2X7R), and exposure to ATP led to high-frequency spiking,
      irreversible increases in cytosolic calcium and cell death. To assess the
      potential effect of P2X7R blockade in ameliorating acute spinal cord injury
      (SCI), we delivered P2X7R antagonists OxATP or PPADS to rats after acute impact
      injury. We found that both OxATP and PPADS significantly improved functional
      recovery and diminished cell death in the peritraumatic zone. These observations
      demonstrate that SCI is associated with prolonged purinergic receptor activation,
      which results in excitotoxicity-based neuronal degeneration. P2X7R antagonists
      inhibit this process, reducing both the histological extent and functional
      sequelae of acute SCI.

PMID- 15258578
TI  - T cells express a phagocyte-type NADPH oxidase that is activated after T cell
      receptor stimulation.
AB  - T cell receptor (TCR) stimulation induces rapid generation of reactive oxygen
      species, although the mechanisms for this are unclear. Here we found that T cells
      expressed a functional phagocyte-type nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase. TCR crosslinking induced oxidase activation through the
      recruitment of preformed Fas ligand and Fas. TCR stimulation induced three
      separable events generating reactive oxygen species: rapid hydrogen peroxide
      production independent of Fas or NADPH oxidase; sustained hydrogen peroxide
      production dependent on both Fas and NADPH oxidase; and delayed superoxide
      production that was dependent on Fas ligand and Fas yet independent of NADPH
      oxidase. NADPH oxidase-deficient T cells showed enhanced activation of the kinase
      Erk and a relative increase in T helper type 1 cytokine secretion. Thus, mature T
      cells express a phagocyte-type NADPH oxidase that regulates elements of TCR
      signaling.

PMID- 15258579
TI  - B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends
      on Pax5.
AB  - Immunoglobulin heavy chain rearrangement (V(H)-to-DJ(H)) occurs only in B cells,
      suggesting it is inhibited in other lineages. Here we found that in the mouse
      V(H) locus, methylation of lysine 9 on histone H3 (H3-K9), a mark of inactive
      chromatin, was present in non-B lineage cells but was absent in B cells. As
      others have shown that H3-K9 methylation can inhibit V(D)J recombination on
      engineered substrates, our data support the idea that H3-K9 methylation inhibits
      endogenous V(H)-to-DJ(H) recombination. We also show that Pax5, a transcription
      factor required for B cell commitment, is necessary and sufficient for the
      removal of H3-K9 methylation in the V(H) locus and provide evidence that one
      function of Pax5 is to remove this inhibitory modification by a mechanism of
      histone exchange, thus allowing B cell-specific V(H)-to-DJ(H) recombination.

PMID- 15258580
TI  - An X-to-autosome retrogene is required for spermatogenesis in mice.
AB  - We identified the gene carrying the juvenile spermatogonial depletion mutation
      (jsd), a recessive spermatogenic defect mapped to mouse chromosome 1 (refs. 1,2).
      We localized jsd to a 272-kb region and resequenced this area to identify the
      underlying mutation: a frameshift that severely truncates the predicted protein
      product of a 2.3-kb genomic open reading frame. This gene, Utp14b, evidently
      arose through reverse transcription of an mRNA from an X-linked gene and
      integration of the resulting cDNA into an intron of an autosomal gene, whose
      promoter and 5' untranslated exons are shared with Utp14b. To our knowledge,
      Utp14b is the first protein-coding retrogene to be linked to a recessive
      mammalian phenotype. The X-linked progenitor of Utp14b is the mammalian ortholog
      of yeast Utp14, which encodes a protein required for processing of pre-rRNA and
      hence for ribosome assembly. Our findings substantiate the hypothesis that
      mammalian spermatogenesis is supported by autosomal retrogenes that evolved from
      X-linked housekeeping genes to compensate for silencing of the X chromosome
      during male meiosis. We find that Utp14b-like retrogenes arose independently and
      were conserved during evolution in at least four mammalian lineages. This
      recurrence implies a strong selective pressure, perhaps to enable ribosome
      assembly in male meiotic cells.

PMID- 15258581
TI  - Mutations in EFHC1 cause juvenile myoclonic epilepsy.
AB  - Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand
      mal seizures. We previously mapped and narrowed a region associated with JME on
      chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1,
      which encodes a protein with an EF-hand motif. Mutation analyses identified five
      missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave
      in affected members of six unrelated families with JME and did not occur in 382
      control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture
      neurons induced apoptosis that was significantly lowered by the mutations.
      Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage
      dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials
      overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C
      terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+)
      currents that were reversed by the mutations associated with JME.

PMID- 15258582
TI  - Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause
      childhood-onset severe retinal dystrophy.
AB  - We identified three consanguineous Austrian kindreds with 15 members affected by
      autosomal recessive childhood-onset severe retinal dystrophy, a genetically
      heterogeneous group of disorders characterized by degeneration of the
      photoreceptor cells. A whole-genome scan by microarray analysis of single
      nucleotide polymorphisms (ref. 2) identified a founder haplotype and defined a
      critical interval of 1.53 cM on chromosome 14q23.3-q24.1 that contains the gene
      associated with this form of retinal dystrophy. RDH12 maps in this region and
      encodes a retinol dehydrogenase proposed to function in the visual cycle. A
      homozygous 677A-->G transition (resulting in Y226C) in RDH12 was present in all
      affected family members studied, as well as in two Austrian individuals with
      sporadic retinal dystrophy. We identified additional mutations in RDH12 in 3 of
      89 non-Austrian individuals with retinal dystrophy: a 5-nucleotide deletion
      (806delCCCTG) and the transition 565C-->T (resulting in Q189X), each in the
      homozygous state, and 146C-->T (resulting in T49M) and 184C-->T (resulting in
      R62X) in compound heterozygosity. When expressed in COS-7 cells, Cys226 and Met49
      variants had diminished and aberrant activity, respectively, in interconverting
      isomers of retinol and retinal. The severe visual impairment of individuals with
      mutations in RDH12 is in marked contrast to the mild visual deficiency in
      individuals with fundus albipunctatus caused by mutations in RDH5, encoding
      another retinal dehydrogenase. Our studies show that RDH12 is associated with
      retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the
      photoreceptor cells.

PMID- 15258583
TI  - VEGF links hippocampal activity with neurogenesis, learning and memory.
AB  - An enriched environment is associated with hippocampal plasticity, including
      improved cognitive performance and increased neurogenesis. Here, we show that
      hippocampal expression of vascular endothelial growth factor (VEGF) is increased
      by both an enriched environment and performance in a spatial maze. Hippocampal
      gene transfer of VEGF in adult rats resulted in approximately 2 times more
      neurogenesis associated with improved cognition. In contrast, overexpression of
      placental growth factor, which signals through Flt1 but not kinase insert domain
      protein receptors (KDRs), had negative effects on neurogenesis and inhibited
      learning, although it similarly increased endothelial cell proliferation.
      Expression of a dominant-negative mutant KDR inhibited basal neurogenesis and
      impaired learning. Coexpression of mutant KDR antagonized VEGF-enhanced
      neurogenesis and learning without inhibiting endothelial cell proliferation.
      Furthermore, inhibition of VEGF expression by RNA interference completely blocked
      the environmental induction of neurogenesis. These data support a model in which
      VEGF, acting through KDR, mediates the effect of the environment on neurogenesis
      and cognition.

PMID- 15258584
TI  - A constitutively active cryptochrome in Drosophila melanogaster.
AB  - Light-activated cryptochrome (CRY) regulates circadian photoresponses in
      Drosophila melanogaster. Removing the carboxy (C) terminus to create CRYDelta
      produces, in yeast, a light-independent, constitutively active form. Here we show
      that flies overexpressing CRYDelta have a longer free-running period of locomotor
      activity, as well as altered cycling kinetics of the clock proteins timeless
      (TIM) and period (PER). Moreover, at the cellular level, they show a reduction in
      the level of TIM and in the nuclear localization of TIM and PER in two
      significant clusters of behavioral pacemaker cells: the large and the small
      ventral lateral neurons (LN(v)s). These effects are similar to those seen in wild
      type flies under continuous light and suggest a regulatory role for the C
      terminus of CRY on the photosensitive, photolyase-like part of the protein.

PMID- 15258585
TI  - A morphological basis for orientation tuning in primary visual cortex.
AB  - Feedforward connections are thought to be important in the generation of
      orientation-selective responses in visual cortex by establishing a bias in the
      sampling of information from regions of visual space that lie along a neuron's
      axis of preferred orientation. It remains unclear, however, which structural
      elements-dendrites or axons-are ultimately responsible for conveying this
      sampling bias. To explore this question, we have examined the spatial arrangement
      of feedforward axonal connections that link non-oriented neurons in layer 4 and
      orientation-selective neurons in layer 2/3 of visual cortex in the tree shrew.
      Target sites of labeled boutons in layer 2/3 resulting from focal injections of
      biocytin in layer 4 show an orientation-specific axial bias that is sufficient to
      confer orientation tuning to layer 2/3 neurons. We conclude that the anisotropic
      arrangement of axon terminals is the principal source of the orientation bias
      contributed by feedforward connections.

PMID- 15258586
TI  - The type 1 equilibrative nucleoside transporter regulates ethanol intoxication
      and preference.
AB  - Adenosine is an important mediator of ethanol intoxication. In vitro, ethanol
      stimulates adenosine signaling by inhibiting the type 1 equilibrative nucleoside
      transporter (ENT1), whereas chronic ethanol exposure downregulates ENT1. It is
      not known, however, whether ENT1 is important for ethanol intoxication or
      consumption in vivo. Here we report that ENT1-null mice show reduced hypnotic and
      ataxic responses to ethanol and greater consumption of alcohol as compared with
      their wild-type littermates. These features are associated with a decrease in
      adenosine tone, as measured indirectly as a reduction in A(1) receptor-mediated
      inhibition of glutamate excitatory postsynaptic currents (EPSCs) in the nucleus
      accumbens, leading to increased phosphorylation of CRE-binding protein (CREB) in
      the striatum. Treatment with an A(1) receptor agonist decreases EPSC amplitude
      and reduces ethanol consumption in ENT1-null mice. Our results indicate that ENT1
      has a physiological role in ethanol-mediated behaviors and suggest that decreased
      A(1) adenosine receptor function promotes alcohol consumption.

PMID- 15258587
TI  - Abnormal cortical voice processing in autism.
AB  - Impairments in social interaction are a key feature of autism and are associated
      with atypical social information processing. Here we report functional magnetic
      resonance imaging (fMRI) results showing that individuals with autism failed to
      activate superior temporal sulcus (STS) voice-selective regions in response to
      vocal sounds, whereas they showed a normal activation pattern in response to
      nonvocal sounds. These findings suggest abnormal cortical processing of socially
      relevant auditory information in autism.

PMID- 15258588
TI  - Rapid vesicular translocation and insertion of TRP channels.
AB  - The broadly expressed transient receptor potential (TRP) family of ion channels
      are permeant to cations, most resulting in increased intracellular calcium.
      However, their regulation and gating is not well understood. Here, we report that
      growth factor stimulation initiates the rapid translocation of the transient
      receptor potential ion channel, TRPC5, from vesicles held in reserve just under
      the plasma membrane. This process, which we term 'rapid vesicular insertion of
      TRP' (RiVIT), dramatically increases membrane-associated TRPC5 channels and
      functional TRPC5 current, resulting in tight spatial-temporal control of these
      Ca(2+)-permeant nonselective channels. Epidermal growth factor (EGF)-induced
      incorporation of functional TRP channels requires phosphatidylinositide 3-kinase
      (PI(3)K), the Rho GTPase Rac1 and phosphatidylinositol 4-phosphate 5-kinase
      (PIP(5)K alpha). The increase in TRPC5 availability affects neurite extension
      rates in cultured hippocampal neurons, and may be a general mechanism for
      initiating Ca(2+) influx and cell morphological changes in response to stimuli.

PMID- 15258589
TI  - MLK3 is required for mitogen activation of B-Raf, ERK and cell proliferation.
AB  - The ERK group of mitogen-activated protein kinases (MAPKs) is essential for cell
      proliferation stimulated by mitogens, oncogenic ras and raf (ref. 1). All MAPKs
      are activated by MAP3K/MEK/MAPK core pathways and the Raf proto-oncoproteins,
      especially B-Raf, are ERK-specific MAP3Ks (refs 1-3). Mixed lineage kinase-3
      (MLK3) is a MAP3K that was thought to be a cytokine-activated, and comparatively
      selective, regulator of the JNK group of MAPKs (refs 1, 4-6). Here we report that
      silencing of mlk3 by RNAi suppressed mitogen and cytokine activation not only of
      JNK but of ERK and p38 as well. Silencing mlk3 also blocked mitogen-stimulated
      phosphorylation of B-Raf at Thr 598 and Ser 601, a step required for B-Raf
      activation. Furthermore, silencing mlk3 prevented serum-stimulated cell
      proliferation and the proliferation of tumour cells bearing either oncogenic Ki
      Ras or loss-of-function neurofibromatosis-1 (NF1) or NF2 mutations. The
      proliferation of tumour cells containing activating B-raf or raf-1 mutations was
      unaffected by silencing mlk3. Our results define an unexpected role for MLK3 in
      mitogen regulation of B-Raf, ERK and cell proliferation.

PMID- 15258590
TI  - Neogenin mediates the action of repulsive guidance molecule.
AB  - Repulsive guidance molecule (RGM) is a recently identified protein implicated in
      both axonal guidance and neural tube closure. The avoidance of chick RGM in the
      posterior optic tectum by growing temporal, but not nasal, retinal ganglion cell
      axons is thought to contribute to visual map formation. In contrast to ephrins,
      semaphorins, netrins and slits, no receptor mechanism for RGM action has been
      defined. Here, an expression cloning strategy identified neogenin as a binding
      site for RGM, with a sub-nanomolar affinity. Consistent with selective axonal
      responsiveness to RGM, neogenin is expressed in a gradient across the chick
      retina. Neogenin is known to be one of several netrin-binding proteins but only
      neogenin interacts with RGM. The avoidance of RGM by temporal retinal axons is
      blocked by the anti-neogenin antibody and the soluble neogenin ectodomain. Dorsal
      root ganglion axons are unresponsive to RGM but are converted to a responsive
      state by neogenin expression. Thus, neogenin functions as an RGM receptor.

PMID- 15258591
TI  - RGM and its receptor neogenin regulate neuronal survival.
AB  - Repulsive guidance molecule (RGM) is an axon guidance protein that repels retinal
      axons upon activation of the neogenin receptor. To understand the functions of
      RGM-neogenin complexes in vivo, we used gene transfer technology to perturb their
      expression in the developing neural tube of chick embryos. Surprisingly, neogenin
      over-expression or RGM down-expression in the neural tube induces apoptosis.
      Neogenin pro-apoptotic activity in immortalized neuronal cells and in the neural
      tube is associated with the cleavage of its cytoplasmic domain by caspases. Thus
      neogenin is a dependence receptor inducing cell death in the absence of RGM,
      whereas the presence of RGM inhibits this effect.

PMID- 15258592
TI  - The neurotrophin-receptor-related protein NRH1 is essential for convergent
      extension movements.
AB  - Early spherical Xenopus laevis embryos are transformed into a streamlined shape
      through convergent extension movements. Here we report that a p75(NTR)-related
      transmembrane protein, NRH1, has an essential function in the regulation of these
      movements. NRH1 was expressed in marginal zone tissues of the gastrula and in the
      posterior ectoderm of the neurula. Attenuation of the NRH1 function inhibited
      convergent extension movements in the embryo and in activin-treated animal caps.
      NRH1 activated downstream effectors of the Wnt/planar cell polarity pathway:
      small GTPases and the cascade of MKK7-JNK. Furthermore, gain- and loss-of
      function phenotypes of NRH1 were rescued by co-injection of dominant-negative and
      constitutively active forms of these downstream effectors, respectively,
      suggesting that NRH1 functions as a positive modulator of planar cell polarity
      signalling. Interestingly, NRH1 does not require Dishevelled (Xdsh) for the
      activation of these downstream effectors or translocation of Xdsh to the
      membrane, suggesting that NRH1 signalling interacts with planar cell polarity
      signalling downstream of Xdsh. This demonstrates an essential role for p75(NTR)
      related signalling in early embryonic morphogenesis.

PMID- 15258593
TI  - Direct proteomic mapping of the lung microvascular endothelial cell surface in
      vivo and in cell culture.
AB  - Endothelial cells can function differently in vitro and in vivo; however, the
      degree of microenvironmental modulation in vivo remains unknown at the molecular
      level largely because of analytical limitations. We use multidimensional protein
      identification technology (MudPIT) to identify 450 proteins (with three or more
      spectra) in luminal endothelial cell plasma membranes isolated from rat lungs and
      from cultured rat lung microvascular endothelial cells. Forty-one percent of
      proteins expressed in vivo are not detected in vitro. Statistical analysis
      measuring reproducibility reveals that seven to ten MudPIT measurements are
      necessary to achieve > or =95% confidence of analytical completeness with current
      ion trap equipment. Large-scale mapping of the proteome of vascular endothelial
      cell surface in vivo, as demonstrated here, is advisable because distinct protein
      expression is apparently regulated by the tissue microenvironment that cannot yet
      be duplicated in standard cell culture.

PMID- 15258594
TI  - In vivo cancer targeting and imaging with semiconductor quantum dots.
AB  - We describe the development of multifunctional nanoparticle probes based on
      semiconductor quantum dots (QDs) for cancer targeting and imaging in living
      animals. The structural design involves encapsulating luminescent QDs with an ABC
      triblock copolymer and linking this amphiphilic polymer to tumor-targeting
      ligands and drug-delivery functionalities. In vivo targeting studies of human
      prostate cancer growing in nude mice indicate that the QD probes accumulate at
      tumors both by the enhanced permeability and retention of tumor sites and by
      antibody binding to cancer-specific cell surface biomarkers. Using both
      subcutaneous injection of QD-tagged cancer cells and systemic injection of
      multifunctional QD probes, we have achieved sensitive and multicolor fluorescence
      imaging of cancer cells under in vivo conditions. We have also integrated a whole
      body macro-illumination system with wavelength-resolved spectral imaging for
      efficient background removal and precise delineation of weak spectral signatures.
      These results raise new possibilities for ultrasensitive and multiplexed imaging
      of molecular targets in vivo.

PMID- 15258595
TI  - Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation.
AB  - Dendrimers are hyperbranched macromolecules that can be chemically synthesized to
      have precise structural characteristics. We used anionic, polyamidoamine,
      generation 3.5 dendrimers to make novel water-soluble conjugates of D(+)
      glucosamine and D(+)-glucosamine 6-sulfate with immuno-modulatory and
      antiangiogenic properties respectively. Dendrimer glucosamine inhibited Toll-like
      receptor 4-mediated lipopolysaccharide induced synthesis of pro-inflammatory
      chemokines (MIP-1 alpha, MIP-1 beta, IL-8) and cytokines (TNF-alpha, IL-1 beta,
      IL-6) from human dendritic cells and macrophages but allowed upregulation of the
      costimulatory molecules CD25, CD80, CD83 and CD86. Dendrimer glucosamine 6
      sulfate blocked fibroblast growth factor-2 mediated endothelial cell
      proliferation and neoangiogenesis in human Matrigel and placental angiogenesis
      assays. When dendrimer glucosamine and dendrimer glucosamine 6-sulfate were used
      together in a validated and clinically relevant rabbit model of scar tissue
      formation after glaucoma filtration surgery, they increased the long-term success
      of the surgery from 30% to 80% (P = 0.029). We conclude that synthetically
      engineered macromolecules such as the dendrimers described here can be tailored
      to have defined immuno-modulatory and antiangiogenic properties, and they can be
      used synergistically to prevent scar tissue formation.

PMID- 15258596
TI  - Systematic identification of abundant A-to-I editing sites in the human
      transcriptome.
AB  - RNA editing by members of the ADAR (adenosine deaminases acting on RNA) family
      leads to site-specific conversion of adenosine to inosine (A-to-I) in precursor
      messenger RNAs. Editing by ADARs is believed to occur in all metazoa, and is
      essential for mammalian development. Currently, only a limited number of human
      ADAR substrates are known, whereas indirect evidence suggests a substantial
      fraction of all pre-mRNAs being affected. Here we describe a computational search
      for ADAR editing sites in the human transcriptome, using millions of available
      expressed sequences. We mapped 12,723 A-to-I editing sites in 1,637 different
      genes, with an estimated accuracy of 95%, raising the number of known editing
      sites by two orders of magnitude. We experimentally validated our method by
      verifying the occurrence of editing in 26 novel substrates. A-to-I editing in
      humans primarily occurs in noncoding regions of the RNA, typically in Alu
      repeats. Analysis of the large set of editing sites indicates the role of editing
      in controlling dsRNA stability.

PMID- 15258597
TI  - De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB
      signalling.
AB  - NF-kappaB transcription factors mediate the effects of pro-inflammatory cytokines
      such as tumour necrosis factor-alpha and interleukin-1beta. Failure to
      downregulate NF-kappaB transcriptional activity results in chronic inflammation
      and cell death, as observed in A20-deficient mice. A20 is a potent inhibitor of
      NF-kappaB signalling, but its mechanism of action is unknown. Here we show that
      A20 downregulates NF-kappaB signalling through the cooperative activity of its
      two ubiquitin-editing domains. The amino-terminal domain of A20, which is a de
      ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63
      (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an
      essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The
      carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then
      functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked
      ubiquitin chains, thereby targeting RIP for proteasomal degradation. Here we
      define a novel ubiquitin ligase domain and identify two sequential mechanisms by
      which A20 downregulates NF-kappaB signalling. We also provide an example of a
      protein containing separate ubiquitin ligase and DUB domains, both of which
      participate in mediating a distinct regulatory effect.

PMID- 15258598
TI  - Chronic pneumonia despite adaptive immune response to Mycobacterium bovis BCG in
      MyD88-deficient mice.
AB  - To assess the role of Toll-like receptor (TLR) signalling in host response to
      mycobacterial infection, mice deficient in the TLR adaptor molecule myeloid
      differentiation factor 88 (MyD88) were infected with the vaccine strain
      Mycobacterium bovis (BCG), and the immune response and bacterial burden were
      investigated. Macrophages and dendritic cells from MyD88-deficient mice
      stimulated in vitro with BCG mycobacterial antigens produced very low levels of
      proinflammatory cytokines, while the expression of costimulatory molecules such
      as CD40 and CD86 was preserved. Upon systemic infection with BCG (2 x 10(6) CFU
      i.v.) MyD88-deficient mice developed confluent chronic pneumonia with two log
      higher CFU than wild-type mice. Interestingly, the infection was controlled in
      liver and spleen and there was efficient systemic T-cell priming with high
      IFNgamma production by CD4+ splenic T cells in MyD88-deficient mice. Lung
      infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon
      specific restimulation, and a reduced capacity to produce nitric oxide and IL-10.
      In summary, despite the dramatic reduction of the innate immune response, MyD88
      deficient mice were able to mount an efficient T-cell response to mycobacterial
      antigens, which was however insufficient to control infection in the lung,
      resulting in chronic pneumonia in MyD88-deficient mice.

PMID- 15258599
TI  - Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial
      mesenchymal transition of lens epithelium in mice.
AB  - We examined the effect of adenovirus-mediated transient expression of Smad7, an
      inhibitory Smad in TGFbeta/activin signaling, on injury-induced epithelial
      mesenchymal transition (EMT) of lens epithelium in mice. A volume of 3 microl of
      adenoviral solution was injected into the right lens of adult male C57BL/6 mice
      (n=56) at the time of capsular injury made using a hypodermic needle under
      general anesthesia. A mixture of recombinant adenovirus carrying CAG promoter
      driven Cre (Cre adv) and mouse Smad7 complementary DNA (Smad7 adv) was
      administered to induce Smad7 expression, while control lenses were treated with
      Cre adv alone. After healing intervals of 2, 3, 5, and 10 days, animals were
      killed 2 h after labeling with bromodeoxyuridine (BrdU) and eyes were processed
      for histology. During healing, marked expression of Smad7 was observed in lens
      epithelial cells in the Smad7 adv group with loss of nuclear translocation of
      Smads2/3, while little Smad7 and abundant nuclear Smads2/3 were seen in cells in
      the Cre adv group. Lens epithelial cells in the Cre adv control group exhibited a
      fibroblastic appearance at days 5 and 10 and the capsular break was sealed with
      fibrous tissue, while Smad7 adv-treated cells around the capsular break retained
      their epithelial morphology and the break was not sealed. Expression of snail
      mRNA, and alpha-smooth muscle actin, lumican, and collagen VI proteins, markers
      of EMT, was observed in control-treated eyes, but not in cells of the Smad7 adv
      group at day 5 with minimal expression at day 10. Additionally, cell
      proliferation increased in epithelium infected with Smad7 adv consistent with
      suppression of injury-induced upregulation of TGFbeta1 in epithelium. We conclude
      that gene transfer of Smad7 in mice prevents injury-induced EMT of lens
      epithelial cells and sealing of the capsular break with fibrous tissue.

PMID- 15258600
TI  - The Ahmed Glaucoma Valve in refractory glaucoma: experiences in Indian eyes.
AB  - PURPOSE: To evaluate the efficacy of the Ahmed Glaucoma Valve implant in
      refractory glaucomas in Indian eyes. MATERIALS AND METHODS: A retrospective
      review was conducted on the charts of 122 eyes of 122 patients with refractory
      glaucoma treated with Ahmed Glaucoma Valve implant placement at Guru Nanak Eye
      Centre, New Delhi between January 1996 and December 1999. The main outcome
      measure was success at the last follow-up. Success was defined as an intraocular
      pressure (IOP) of 22 mmHg or less and 5 mmHg or more and at least a 30% reduction
      in IOP without visually devastating complications or additional glaucoma surgery.
      RESULTS: The mean postoperative IOP (17.29+/-3.79 mmHg) was significantly
      (P<0.001) lower than the mean preoperative IOP (31.47+/-7.86 mmHg) at last follow
      up (mean 12.51+/-8.37 months; range 3-24 months). The cumulative probability of
      success by Kaplan-Meier analysis was 85.95% at 12 months and 82.83% at 24 months.
      The mean number of postoperative antiglaucoma medications (0.75+/-0.80) was also
      significantly lower (P<0.001) than the mean preoperative number of antiglaucoma
      medications (2.83+0.72). The most common complication was corneal-tube contact,
      which occurred in five (4.10%) eyes. Retinal detachment occurred postoperatively
      in one eye with the clinical diagnosis of neovascular glaucoma secondary to
      Eale's disease. Two patients had tube extrusion requiring repositioning and
      reinforcement with scleral patch graft. CONCLUSIONS: Ahmed Glaucoma Valve
      implantation is an effective and relatively safe therapy for the treatment of
      refractory glaucoma in Indians.

PMID- 15258601
TI  - Foveal avascular zone in diabetic retinopathy: quantitative vs qualitative
      assessment.
AB  - PURPOSE: To describe the relations between foveal avascular zone (FAZ) size and
      outline in patients presenting diabetic retinopathy. METHODS: 110 high-quality
      fluorescein angiograms from 110 diabetics were chosen from our digital retinal
      image databank. Patients with significant media opacities, macular scars, macular
      hard exsudates, high ametropia, and associated macular pathology were excluded.
      Both FAZ perimeter and surface area were measured with image analysis software.
      FAZ outline was graded according to ETDRS report Number 11 (from 0=normal to
      4=capillary outline completely destroyed). Data were compared to that of 31
      healthy controls. FAZ surface in diabetics was compared to that of controls and
      FAZ surface was compared to FAZ grade, FAZ perimeter and retinopathy stage in
      diabetics. Quantitative variables were compared using the U-test of Mann-Whitney
      or Kruskal-Wallis test and correlations between quantitative variables were
      estimated with the Spearmann coefficient. RESULTS: All patients presented
      diabetic retinopathy (54 BDR, 30 PPDR, 26 PDR). FAZ size was larger in diabetics
      than controls (P<0.001). In diabetics, FAZ size increased with FAZ grade
      (P<or=0.006 except between grades 1 and 2=NS) and with retinopathy stage
      (P<or=0.024). As retinopathy advanced, there was a higher proportion of altered
      FAZ outlines (P=0.003). CONCLUSIONS: This study confirms capillary alteration to
      be the cause of increase in FAZ size in diabetics and presents an alternative
      evaluation method of the FAZ to FAZ size measurement. No qualitative studies
      using the ETDRS FAZ grading scale have been performed to our knowledge.

PMID- 15258602
TI  - The successful use of infliximab in resistant relapsing polychondritis and
      associated scleritis.

PMID- 15258603
TI  - Varying effects of corneal thickness on intraocular pressure measurements with
      different tonometers.
AB  - AIMS: To compare the intraocular pressure (IOP) measurements using the Goldmann
      applanation tonometer (GAT), noncontact tonometer (NCT), and ocular blood flow
      tonometer (OBFT), and to evaluate the effects of varying central corneal
      thickness (CCT) on the readings. METHODS: Ultrasound pachymetry and tonometry
      were performed on 170 eyes. Using the corrected GAT values that took CCT into
      account as the standard, we calculated the NCT and OBFT measurement errors
      related to the CCT variable by a linear regression model. Group comparisons were
      performed with the chi2 test and one-way ANOVA test. The correlation between the
      various tonometer measurements was analysed by Pearson's correlation method.
      RESULTS: Both the NCT (r=0.872, P<0.001) and OBFT measurements (r=0.861, P<0.001)
      were highly correlated with the GAT measurements. IOP measurements using the
      three tonometers were all correlated with CCT (all P<0.001), with the NCT
      measurements showing the greatest regression coefficient (beta=0.063, r=0.650)
      and the GAT measurements the least (beta=0.037, r=0.496). A linear regression
      model indicated that a 10 microm change in CCT resulted in a NCT measurement
      deviation of 0.47-0.98 mmHg and an OBFT measurement deviation of 0.29-0.81 mmHg.
      CONCLUSION: Pressure readings with the GAT, NCT, and OBFT are all affected by
      CCT, with the NCT being the one most affected and the GAT the least. Our findings
      suggest CCT an essential variable to consider in interpreting IOP readings,
      especially for the NCT measurements.

PMID- 15258604
TI  - Ultrastructure of vitreomacular traction syndrome associated with persistent
      hyaloid artery.
AB  - AIM: To demonstrate the ultrastructure of vitreomacular traction associated with
      persistent hyaloid artery. METHODS: Pars plana vitrectomy was performed in a 66
      year-old man with progressive vitreomacular traction associated with a persistent
      hyaloid artery. Epimacular tissue was peeled and processed for transmission
      electron microscopy. RESULTS: Ultrastructural analysis revealed multiple sheets
      of cellular and collagenous components. Myofibroblasts and newly formed collagen
      were the predominant features. Fibrous astrocytes, fibroblasts, macrophages, and
      basement membrane were also present. CONCLUSION: The cellular composition of the
      epimacular tissue and high cellular activity suggest that persistence of the
      hyaloid artery may contribute to the development of vitreomacular traction.

PMID- 15258605
TI  - Bilateral acute uveitis and conjunctivitis after zoledronic acid therapy.

PMID- 15258606
TI  - Multifocal electroretinogram and optical coherence tomography of commotio retinae
      and traumatic macular hole.

PMID- 15258607
TI  - Retinal detachment following surgery for congenital cataract: presentation and
      outcomes.
AB  - AIMS: To review the current management and outcomes of retinal detachment
      following cataract surgery in childhood. METHODS: A retrospective review of 59
      eyes of 52 patients. RESULTS: In 37% of patients, the fellow eye was blind
      (<3/60). The macula was detached at presentation in 81% of eyes. The detachment
      was obscured by residual lens matter, or a miotic pupil in 67% of eyes that had
      cataract surgery before 1970, but in only 30% of eyes operated after 1970. The
      retina was reattached with one operation in 59% of eyes, and final reattachment
      was achieved in 81%. No retina was reattached by scleral buckling alone. Visual
      outcomes were slightly better in eyes that had retinal detachment repair after 1
      January 1998. Nine patients were blind in both eyes at the latest follow-up.
      CONCLUSIONS: Retinal detachment following childhood cataract surgery remains a
      serious condition. There has been some improvement in the prognosis due to a
      combination of advances in childhood cataract surgery as well as to improvements
      in the management of retinal detachment. Early recognition and prompt surgery,
      using an internal approach, may prevent blindness in most cases.

PMID- 15258608
TI  - Underestimating the importance of amblyopia: flawed methodology?

PMID- 15258609
TI  - Relationship of gender, body mass index, and axial length with central retinal
      thickness using optical coherence tomography.
AB  - BACKGROUND: Optical coherence tomography (OCT) acquires cross-sectional retinal
      images with high resolution using low-coherence interferometry. Few studies have
      studied the effect of demographic data and ocular parameters that may affect
      central retinal thickness. In this study, these factors were used as parameters
      to analyse if any significant relationship exists with central retinal thickness.
      METHODS: Volunteers with a best-corrected visual acuity of 6/12 or better and no
      evidence of ocular abnormalities or interventions were recruited from October
      2001 to March 2003. Body mass index (BMI), autorefraction, and keratometry
      recordings were measured, followed by applanation tonometry and A-scan
      ultrasonography. The central retinal thickness of the right eye was analysed
      using a scan length of 3 cm. Another 25 eyes were selected for interobserver
      reproducibility. RESULTS: In all, 117 normal subjects (60 male and 57 female
      subjects) were recruited. The mean thickness of the central retina with a
      diameter of 1 mm was 203+/-23 microm for male and 189+/-20 microm for female
      subjects. Age, intraocular pressure, and keratometric readings were not
      significantly correlated with central retinal thickness. Using multiple
      regression, gender, BMI, axial length, and signal-to-noise ratio (P<0.05) were
      significantly associated with the central retinal thickness. The intraclass
      correlation coefficient was 0.98 for interobserver reproducibility. CONCLUSION:
      OCT has a high interobserver reproducibility. The male gender, larger BMI, and
      longer axial length are associated with a significantly thicker central retina
      and these parameters should be considered for assessing retinal thickening and
      baseline comparisons in future studies.

PMID- 15258610
TI  - Deep sclerectomy in one eye vs deep sclerectomy with collagen implant in the
      contralateral eye of the same patient: long-term follow-up.
AB  - PURPOSE: To compare prospectively the results of deep sclerectomy (DS) vs deep
      sclerectomy with collagen implant (DSCI). METHODS: Randomized prospective trial
      involving 26 eyes (13 patients) with medically uncontrolled primary and secondary
      open angle glaucoma. Collagen implant was randomly assigned to one eye of each
      patient. RESULTS: The mean follow-up period was 49.5 (SD 20) months for the DS
      treated eyes, and 56.5 (SD 14) months for the DSCI-treated eyes (P=0.4). The mean
      preoperative intraocular pressure (IOP) was 24.1 (SD 7) mmHg for the DS-treated
      eyes, and 25.3 (SD 6) mmHg for the DSCI-treated eyes (P=0.5). The mean IOP at the
      first postoperative day was 6.4 (SD 3) mmHg for the DS-treated eyes, and 3.7 (SD
      2) mmHg for the DSCI-treated eyes (P=0.05). The mean IOP at 12 months
      postoperative day was 15.4 (SD 3) mmHg for the DS group, and 10.4 (SD 4) mmHg for
      the DSCI-treated eyes (P=0.04), while at 48 months it was 16 (SD 3) mmHg for the
      DS group, and 10 (SD 4) mmHg for the DSCI-treated eyes (P=0.005). Complete
      success rate, defined as an IOP lower than 21 mmHg without medication, was 38%
      (5/13 patients) at 48 months for the DS-treated eyes, and 69% (9/13 patients) for
      the DSCI-treated eyes. Qualified success rate: patients who achieved IOP below 21
      mmHg with or without medication, was 69% (9/13 patients) at 48 months and 100%
      (13/13 patients) for the DSCI group. The mean number of medications was reduced
      from 2.4 (SD 0.8) to 1.1 (SD 1) after DS, and was reduced from 2.2 (SD 0.7) to
      0.4 (SD 0.6) in the DSCI group (P=0.001). For those eyes treated with DSCI, IOP
      was 3.21 mmHg lower than for those treated with DS (P<0.0001). CONCLUSION: The
      use of a collagen implant in DS seems to enhance the success rates, provides
      significantly lower IOP levels, and lowers the need for postoperative
      medications.

PMID- 15258611
TI  - Comparing the effects of travoprost and brinzolamide on intraocular pressure
      after phacoemulsification.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP) lowering effect of travoprost
      and brinzolamide within the first 24 h after phacoemulsification cataract
      surgery. METHODS: This prospective, randomized, double-masked, controlled study
      comprised 90 eyes of 90 consecutive patients with senile cataract who had
      uneventful phacoemulsification surgery. Eyes in the first group received
      travoprost 0.0015%, second group received brinzolamide 1%. Eyes in the third
      group received balanced salt solution and were used as control. One drop was
      instilled immediately after surgery. IOP was measured 24 h preoperatively, 6 and
      24 h postoperatively. Analysis of variance, Student's-t and chi2-tests were used
      for statistical analyses. RESULTS: Preoperatively IOP was not significantly
      different among the three groups (P = 0.653). At 6 and 24 h postoperatively IOP
      was lower in both travoprost and brinzolamide group when compared to control
      group (P = 0.018 and 0.015 at 6 h, P = 0.010 and 0.007 at 24 h between travoprost
      and brinzolamide group was not significant (P = 0.744 at 6 h and P = 0.672 at 24
      h). CONCLUSION: Both travoprost and brinzolamide significantly lowered IOP after
      small incision phacoemulsification cataract surgery within the first 24 h without
      any side effect.

PMID- 15258612
TI  - Invasive and noninvasive uveal melanomas have different adhesive properties.
AB  - AIMS: To establish if invasive and noninvasive uveal melanomas have differences
      in expression of adhesion molecules, and whether their adhesive interactions with
      the extracellular matrix (ECM) and endothelium vary. METHODS: Cells from an
      invasive and noninvasive uveal melanoma cell line and hepatic and dermal
      microvascular endothelial cells were assessed by flow cytometry for adhesion
      molecule expression. Tumour cell adhesion to ECM substrates (collagens I and IV,
      fibronectin, laminin, and vitronectin) and endothelial cells was also
      investigated using a commercially available assay or a fluorescence-based in
      vitro assay, respectively. The significance of results comparing cell lines was
      determined using a Student's t-test, whereby P-values of less than 0.05 were
      taken as significant. RESULTS: alpha1- and alpha4-integrins were not expressed by
      noninvasive cells, but were detected on invasive cells. The invasive cell line
      also expressed higher levels of other integrins than the noninvasive line.
      Correspondingly, invasive cells adhered in higher numbers to ECM substrates and
      endothelial cells, and for the latter, the difference was highly significant
      (P<0.001). No preference in adhesion of invasive cells for the hepatic
      endothelium was observed. CONCLUSIONS: Successful attachment to and migration
      through the ECM, basement membrane, and endothelium are vital processes involved
      in malignant progression. Differential expression of alpha1- and alpha4-integrins
      by invasive and noninvasive cells infers a role for these receptors in invasion,
      while the ability of invasive cells to adhere more efficiently to the endothelium
      suggests that this is a critical factor in uveal melanoma invasion.

PMID- 15258613
TI  - Crystal structure of human otubain 2.
AB  - Ubiquitylation, the modification of cellular proteins by the covalent attachment
      of ubiquitin, is critical for diverse biological processes including cell cycle
      progression, signal transduction and stress response. This process can be
      reversed and regulated by a group of proteases called deubiquitylating enzymes
      (DUBs). Otubains are a recently identified family of DUBs that belong to the
      ovarian tumour (OTU) superfamily of proteins. Here, we report the first crystal
      structure of an OTU superfamily protein, otubain 2, at 2.1 A resolution and
      propose a model for otubain-ubiquitin binding on the basis of other DUB
      structures. Although otubain 2 is a member of the cysteine protease superfamily
      of folds, its crystal structure shows a novel fold for DUBs. Moreover, the active
      site cleft is sterically occluded by a novel loop conformation resulting in an
      oxyanion hole, which consists uniquely of backbone amides, rather than the
      composite backbone/side-chain substructures seen in other DUBs and cysteine
      proteases. Furthermore, the residues that orient and stabilize the active-site
      histidine of otubain 2 are different from other cysteine proteases. This
      reorganization of the active-site topology provides a possible explanation for
      the low turnover and substrate specificity of the otubains.

PMID- 15258614
TI  - Analysis of developing maize plastids reveals two mRNA stability classes
      correlating with RNA polymerase type.
AB  - The plastid genome is transcribed by two distinct RNA polymerases, the PEP
      encoded by the plastid genome and the NEP encoded in the nucleus. Initial models
      of plastid transcription held that the NEP is responsible for the transcription
      of housekeeping genes needed early in development, and that the PEP transcribes
      genes required for photosynthesis. Recently, this model was challenged by the
      discovery that all plastid genes are transcribed by NEP in PEP-deficient tobacco
      plastids, suggesting that mRNA turnover may have a strong role in previously
      observed transcription patterns. In this study, we provide evidence that the NEP
      enzyme level decreases as plastids mature. In contrast, production of mRNAs by
      NEP increases as plastids mature, yet their accumulations remain constant. These
      results suggest that as plastids mature NEP may become more active, and that mRNA
      turnover varies between transcripts synthesized by NEP and PEP.

PMID- 15258616
TI  - The manipulation of immunity. Conference on from allergy to cancer: new
      perspectives for therapeutic vaccination.

PMID- 15258615
TI  - Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent protein
      degradation.
AB  - Known activities of the ubiquitin-selective AAA ATPase Cdc48 (p97) require one of
      the mutually exclusive cofactors Ufd1/Npl4 and Shp1 (p47). Whereas Ufd1/Npl4
      recruits Cdc48 to ubiquitylated proteins destined for degradation by the 26S
      proteasome, the UBX domain protein p47 has so far been linked exclusively to
      nondegradative Cdc48 functions in membrane fusion processes. Here, we show that
      all seven UBX domain proteins of Saccharomyces cerevisiae bind to Cdc48, thus
      constituting an entire new family of Cdc48 cofactors. The two major yeast UBX
      domain proteins, Shp1 and Ubx2, possess a ubiquitin-binding UBA domain and
      interact with ubiquitylated proteins in vivo. Deltashp1 and Deltaubx2 strains
      display defects in the degradation of a ubiquitylated model substrate, are
      sensitive to various stress conditions and are genetically linked to the 26S
      proteasome. Our data suggest that Shp1 and Ubx2 are adaptors for Cdc48-dependent
      protein degradation through the ubiquitin/proteasome pathway.

PMID- 15258618
TI  - Dyslipidaemia in South Africa.

PMID- 15258617
TI  - A mechanism for the proapoptotic activity of ursodeoxycholic acid: effects on Bcl
      2 conformation.
AB  - Ursodeoxycholic acid (UDCA), a relatively nontoxic bile acid, enhanced the
      apoptotic response of tumor cells to both photosensitizers that cause photodamage
      to Bcl-2 and to the nonpeptidic Bcl-2/Bcl-x(L) antagonist HA14-1. The latter
      agent binds to the surface pocket formed by the BH1, BH2 and BH3 domains of Bcl-2
      and Bcl-x(L). Fluorescence polarization studies indicated that affinity of HA14-1
      for Bcl-2 was enhanced in the presence of UDCA. Moreover, Bcl-2 photodamage was
      promoted by UDCA using a photosensitizing agent with affinity for the endoplasmic
      reticulum, a site of Bcl-2 localization. Fluorescence resonance energy transfer
      (FRET) studies revealed that the proximity of Bcl-2 to a hydrophobic
      photosensitizing agent embedded in liposomes was enhanced by UDCA. Since
      photodamage will occur only if a protein is in close contact with a
      photosensitizing agent, we propose that these findings support the hypothesis
      that UDCA causes a conformational change in Bcl-2, promoting HA14-1 binding and
      enhancing affinity for certain membrane-bound photosensitizers.

PMID- 15258619
TI  - New development in HDL.

PMID- 15258620
TI  - Lp(a) and apoE polymorphisms in young South African Indians with myocardial
      infarction.
AB  - The lipoprotein(a) [Lp(a)] and apolipoprotein E (apoE) polymorphisms have been
      shown to be important genetic determinants of cardiovascular risk. Their effect
      on coronary heart disease (CHD) is less clear, particularly in Asian Indians who
      are at high risk for this disease. The aim of this study was to examine the
      association of the Lp(a) promoter pentanucleotide repeat polymorphism and the
      apoE codon 112 and 158 genotypes in 195 young South African Indian patients (< or
      = 45 years) with myocardial infarction (MI). Results were compared with 300
      healthy age-matched control subjects drawn from the same community and 107
      unaffected siblings (18-45 years). In addition, fasting lipograms were performed
      on all patients and a detailed history of conventional risk factors and family
      background was obtained. Of the six different Lp(a) alleles detected, the 8
      repeat sequence was most frequently seen. However, no difference in frequencies
      existed between patient and control groups. The most frequently occurring apoE
      genotype in the three study groups was E3/E3 (patients 71%; siblings 70%;
      controls 70%). A significant difference in the E3/E4 genotype was seen between
      patients and controls (23% vs 14%; p = 0.018) and between siblings and controls
      (24% vs 14%; p = 0.027). These patients were also more likely to have
      significantly higher low-density lipoprotein (LDL) and lower high-density
      lipoprotein (HDL) levels (p = 0.005 and 0.045, respectively). No association was
      observed between any of the Lp(a) or apoE genotypes and conventional risk factors
      such as smoking, diabetes, hypertension, obesity or a family history of CHD. In
      conclusion, the apoE3/E4 genotype is strongly associated with the incidence of
      myocardial infarction in young South African Indians. This genotype also
      adversely affects LDL and HDL cholesterol levels, both of which contribute to
      premature atherosclerosis. In contrast, the Lp(a) pentanucleotide repeat
      polymorphism does not appear to have any aetiological role in MI in this
      population.

PMID- 15258621
TI  - A single-centre retrospective observational study to evaluate the change in total
      cholesterol and LDL cholesterol in hyperlipidaemic patients switched from
      atorvastatin to simvastatin.
AB  - The clinical effects of switching from one HMG Co-A reductase inhibitor
      (atorvastatin) to another therapeutic agent within the same class (simvastatin)
      were examined in this observational study. Levels of total-C, LDL-C, HDL-C and
      triglycerides from 100 patients were compared before and after switching, and the
      maintenance, improvement or loss of lipid control was assessed. There was a
      significant increase in total-C and triglycerides (p < 0.05) following the switch
      from atorvastatin to simvastatin. A number of patients showed > or = 10%
      variation in lipid levels after switching. The high intrapatient variation seen
      in this study strongly suggests that therapeutic substitution is associated with
      an unpredictable response in plasma lipid levels and their control. This would
      have practical implications for physicians who are considering a switch of this
      nature.

PMID- 15258622
TI  - Cardiovascular risk factors in type 2 diabetic Nigerians with clinical diabetic
      nephropathy.
AB  - This study aimed to assess the distribution of cardiovascular risk factors among
      subjects with type 2 clinical diabetic nephropathy, since in diabetic subjects,
      the excess mortality in cardiovascular events is primarily related to
      nephropathy. The study group consisted of 162 subjects with type 2 diabetes
      mellitus and persistent proteinuria, and the control group was 80 type 2 diabetic
      subjects without nephropathy. In the study group there were 81 male and 81 female
      subjects whose mean age was 53.4 +/- 6.3 years. There was no significant
      consumption of alcohol and cigarette use in the population. The mean waist-hip
      ratio (WHR) was 0.97 and 0.96 in male and female subjects, respectively. The mean
      body mass index (BMI) of the subjects was 25.5 +/- 5.2 (males: 24.4 +/- 4.3,
      females: 27.2 +/- 5.5). A total of 106 subjects, made up of 45 male (27.8%) and
      61 female (37.7%) subjects, were hypertensive as compared with 16 controls (20%).
      There was a significant difference in systolic blood pressure (p < 0.05) between
      the obese and non-obese subjects. One hundred and thirty three subjects (82.1%)
      had serum total cholesterol below 200 mg% as compared with 74 (92.5% ) in the
      control. Seventy-eight subjects (48.1%) had left ventricular hypertrophy. Males
      had a higher tendency of developing left ventricular hypertrophy (p = 0.04).
      Stroke and peripheral vascular disease respectively occurred more commonly in
      type 2 diabetes mellitus subjects with nephropathy [7 (4%) and 44 (27.2%)]
      compared to type 2 diabetic subjects without nephropathy [0 (0% ) and 9 (11.3% )]
      (p < 0.05). We found that there is a high prevalence of cardiovascular risk
      factors among Nigerian subjects with clinical diabetic nephropathy.

PMID- 15258623
TI  - Progressive familial heart block type II (PFHBII): a clinical profile from 1977
      to 2003.
AB  - An evaluation of a 38-year-old Caucasian woman, who was referred to Tygerberg
      Hospital (Western Cape Province, RSA) with Wenckebach second-degree or possibly
      complete atrioventricular (AV) block that had progressed from first-degree AV
      block, identified a family history of the cardiac conduction system disorder
      progressive familial heart block type II (PFHBII). This prompted a retrospective
      clinical review of the subjects described in the original study, as well as
      additional family members who had not been examined in the original study.
      Progression of clinical features was observed, but more importantly, PFHBII was
      clinically redefined as an AV nodal disorder, which may progress to dilated
      cardiomyopathy (DCM).

PMID- 15258624
TI  - Isolated right ventricular infarction mimicking anterior myocardial infarction
      presenting with cardiogenic shock.
AB  - This is a rare case of an isolated right ventricular infarction (RVI), presenting
      with cardiogenic shock and an electrocardiograph (ECG) mimicking a large anterior
      myocardial infarction. The patient was treated successfully with primary
      percutaneous coronary intervention to a sub-totally occluded co-dominant right
      coronary artery (RCA).

PMID- 15258625
TI  - Cardiac amyloidosis presenting as pseudo-hypertrophic cardiomyopathy.
AB  - Both cardiac amyloidosis and hypertrophic cardiomyopathy may result in excessive
      hypertrophy of the myocardium, which can be seen on echocardiography. While in
      most patients the two conditions are easily differentiated, we present in this
      report a case of amyloidosis that mimicked hypertrophic cardiomyopathy so closely
      that it required endomyocardial biopsy to establish the diagnosis.

PMID- 15258627
TI  - Innateness and the instinct to learn.
AB  - Concepts of innateness were at the heart of Darwin's approach to behavior and
      central to the ethological theorizing of Lorenz and, at least to start with, of
      Tinbergen. Then Tinbergen did an about face, and for some twenty years the term
      'innate' became highly suspect. He attributed the change to Lehrman's famous 1953
      critique in which he asserted that classifying behaviors as innate tells us
      nothing about how they develop. Although Lehrman made many valid points, I will
      argue that this exchange also led to profound misunderstandings that were
      ultimately damaging to progress in research on the development of behavior. The
      concept of 'instincts to learn', receiving renewed support from current
      theorizing among geneticists about phenotypic plasticity, provides a potential
      resolution of some of the controversies that Lehrman created. Bioacoustical
      studies, particularly on song learning in birds, serve both to confirm some of
      Lehrman's anxieties about the term 'innate', but also to make a case that he
      threw out the genetic baby with the bathwater. The breathtaking progress in
      molecular and developmental genetics has prepared the way for a fuller
      understanding of the complexities underlying even the simplest notions of innate
      behavior, necessary before we can begin to comprehend the ontogeny of behavior.

PMID- 15258626
TI  - Cardiovascular complications of acute cocaine poisoning: a clinical case report.
AB  - We present a case of an accidental cocaine overdose with various cardiovascular
      and neurological complications and ECG features of Brugada syndrome. It is
      imperative that clinicians know how to recognise and manage the symptoms of
      cocaine overdose because of the exceedingly rapid progression of the 'cocaine
      reaction' to a fatal outcome.

PMID- 15258628
TI  - From birdsong to speech: a plea for comparative approaches.
AB  - Human language and speech are unique accomplishments. Nevertheless, they share a
      number of characteristics with other systems of communication, and investigators
      have thus compared them to birdsong and the vocal signaling of nonhuman primates.
      Particular interesting parallels concern the development of singing and speaking.
      These behaviors rely on auditory perception, subsequent memorization and finally,
      the generation of vocal imitations. Several mechanisms help young individuals to
      deal with the various challenges during the time of signal development. Specific
      differences aside, astounding parallels can be found also in how a human and a
      particularly accomplished bird like the Common Nightingale Luscinia megarhynchos
      treat the experience of many different sound patterns or songs. As a consequence
      of such exposure, both human infants and young birds eventually acquire large
      repertoires of verbal or vocal signals. These achievements, however, require
      access to specific memory mechanisms which are well adapted to the purposes they
      serve, thereby allowing them to fulfil their species typical roles. With such
      aspects as a reference, birdsong is an excellent biological model for memory
      research and also an appropriate system for the study of evolutionary strategies
      in a very successful class of organisms.

PMID- 15258629
TI  - Rules of song development and their use in vocal interactions by birds with large
      repertoires.
AB  - Songbirds are well known for settling their disputes by vocal signals, and their
      singing plays a dominant role. Most studies on this issue have concentrated on
      bird species that develop and use small vocal repertoires. In this article we
      will go farther and focus on examples of how species with large song repertoires
      make use of their vocal competence. In particular, we will outline the study of
      interaction rules which have been elucidated by examining time- and pattern
      specific relationships between signals exchanged by territorial neighbors. First
      we present an inquiry into the rules of song learning and development. In birds
      with large song repertoires, the ontogeny of such rules proceeds along a number
      of trajectories which help in understanding the often remarkable accomplishments
      of adult birds. In both approaches, our model species will be the Common
      Nightingale Luscinia megarhynchos that has been investigated intensively in the
      field and in the laboratory.

PMID- 15258630
TI  - Approaches to the mechanisms of song memorization and singing provide evidence
      for a procedural memory.
AB  - There is growing evidence that, during song learning, birds do not only acquire
      'what to sing' (the inventory of behavior), but also 'how to sing' (the singing
      program), including order-features of song sequencing. Common Nightingales
      Luscinia megarhynchos acquire such serial information by segmenting long strings
      of heard songs into smaller subsets or packages, by a process reminiscent of the
      chunking of information as a coding mechanism in short term memory. Here we
      report three tutoring experiments on nightingales that examined whether such
      'chunking' was susceptible to experimental cueing. The experiments tested whether
      (1) 'temporal phrasing' (silent intersong intervals spaced out at particular
      positions of a tutored string), or (2) 'stimulus novelty' (groups of novel song
      types added to a basic string), or (3) 'pattern similarity' in the phonetic
      structure of songs (here: sharing of song initials) would induce package
      boundaries (or chunking) at the manipulated sequential positions. The results
      revealed cueing effects in experiments (1) and (2) but not in experiment (3). The
      finding that birds used temporal variables as cues for chunking does not require
      the assumption that package formation is a cognitive strategy. Rather, it points
      towards a mechanism of procedural memory operating in the song acquisition of
      birds.

PMID- 15258631
TI  - Evidence of tutoring in the development of subsong in newly-fledged Meyer's
      Parrots Poicephalus meyeri.
AB  - Subsongs are vocal trials uttered by young birds to practice songs. Among
      songbirds, subsongs are displayed by individuals in their first year of life.
      Studies on Zebra Finches Poephila guttata suggest that the juveniles learn their
      songs from a vocal tutor, their father. In this study we examine the subsongs in
      six captive-born Meyer's Parrots Poicephalus meyeri, from fledging time to
      weaning. Recordings of songs from chicks and fathers were analyzed for
      similarities in frequency and time parameters. With age, the subsongs of the
      chicks became more similar to the vocalizations of the fathers with 20%
      similarity rating in the first week after fledging to 100% at weaning time.
      Moreover, fledged chicks were exposed to a wide range of stimuli from several
      species of parrots breeding pairs caged nearby but chicks exclusively learned
      their fathers' songs. Our data support the hypothesis that Meyer's Parrots are
      vocal learners and use their father as their tutor.

PMID- 15258632
TI  - A memory like a female Fur Seal: long-lasting recognition of pup's voice by
      mothers.
AB  - In colonial mammals like fur seals, mutual vocal recognition between mothers and
      their pup is of primary importance for breeding success. Females alternate
      feeding sea-trips with suckling periods on land, and when coming back from the
      ocean, they have to vocally find their offspring among numerous similar-looking
      pups. Young fur seals emit a 'mother-attraction call' that presents individual
      characteristics. In this paper, we review the perceptual process of pup's call
      recognition by Subantarctic Fur Seal Arctocephalus tropicalis mothers. To
      identify their progeny, females rely on the frequency modulation pattern and
      spectral features of this call. As the acoustic characteristics of a pup's call
      change throughout the lactation period due to the growing process, mothers have
      thus to refine their memorization of their pup's voice. Field experiments show
      that female Fur Seals are able to retain all the successive versions of their
      pup's call.

PMID- 15258633
TI  - Identification and analysis of vocal communication pathways in birds through
      inducible gene expression.
AB  - The immediate-early gene zenk is an activity-dependent gene highly induced in
      auditory processing or vocal motor control brain areas when birds engage in
      hearing or producing song, respectively. Studies of the expression of zenk in
      songbirds and other avian groups will be reviewed here briefly, with a focus on
      how this analysis has generated new insights on the brain pathways and mechanisms
      involved in perceptual and motor aspects of vocal communication and vocal
      learning.

PMID- 15258634
TI  - Vocal mechanisms in birds and bats: a comparative view.
AB  - Vocal signals play a very important role in the life of both birds and
      echolocating bats, but these two unrelated groups of flying vertebrates have very
      different vocal systems. They nevertheless must solve many of the same problems
      in producing sound. This brief review examines avian and microchiropteran motor
      mechanisms for: 1) coordinating the timing of phonation with the vocal motor
      pattern that controls its acoustic properties, and 2) achieving respiratory
      strategies that provide adequate ventilation for pulmonary gas exchange, while
      also facilitating longer duration songs or trains of sonar pulses.

PMID- 15258636
TI  - Are communication activities shaped by environmental constraints in reverberating
      and absorbing forest habitats?
AB  - In the dense vegetation of temperate or tropical forests, communication processes
      are constrained by propagation-induced modifications of the transmitted sounds.
      The presence of leaves, trunks and branches induces important sound reverberation
      and absorption leading to diminution of the signal energy as well as qualitative
      modifications. The aim of this paper is to briefly review the different
      strategies used by birds to manage with these constraints. At the emitter's
      level, an adapted emission behavior which takes into account both the physical
      heterogeneities of the forest environment and the temporal variations of the
      acoustic constraints, is especially useful to control the active space of
      signaling. The coding of information into acoustic parameters that have different
      susceptibility to propagation constraints is also of great interest. At the
      receiver's level, an adaptive reception behavior (listening post) and a great
      tolerance to sound degradation during the decoding process are the keys to an
      optimal communication process.

PMID- 15258635
TI  - Combination sensitivity and processing of communication calls in the inferior
      colliculus of the Moustached Bat Pteronotus parnellii.
AB  - Many animals use complex communication calls in social behaviors. In some species
      we know the features in the calls that elicit particular behaviors, but we do not
      understand how the auditory system encodes the calls. Nor do we understand the
      mechanisms underlying neural selectivity to calls. Our studies of the auditory
      midbrain of the Moustached Bat Pteronotus parnellii have revealed a neural
      mechanism important for generating selective responses to calls. Neurons that
      integrate information across different frequencies show selectivity to
      communication calls. "Combination sensitivity" may be a common mechanism for
      encoding complex sounds because it is also important for encoding echolocation
      signals.

PMID- 15258637
TI  - Degradation of song in a species using nesting holes: the Pied Flycatcher
      Ficedula hypoleuca.
AB  - The habitat, but also the nest hole of a hole-nesting species, will degrade the
      song during transmission. We investigated how the sounds degrade in a sound
      transmission experiment with the song of the Pied Flycatcher Ficedula hypoleuca
      (Muscicapidae). Ten different song elements were transmitted to microphones
      placed inside and outside a nest box. On average, song degradation was much
      greater inside than outside the nest boxes, especially with respect to excess
      attenuation and blurring of the song elements. Being inside a nest box therefore
      strongly reduces a Pied Flycatcher's possibility of detecting and recognizing
      songs or eavesdropping on singing interactions.

PMID- 15258638
TI  - Does the environment constrain avian sound localization?
AB  - A bird needs to keep track not only of social interactions of conspecifics but
      also of their changing locations in space by determining their directions and
      distances. Current knowledge of accuracy in the computation of sound source
      location by birds is still insufficient, partly because physiological mechanisms
      of few species are studied in well defined laboratory settings, while field
      studies are performed in a variety of species and complex environments. Velocity
      gradients and reverberating surfaces may conceivably induce inaccuracy in sound
      source location (mainly elevation) by distorting the directional cues. However,
      most birds possess an inherently directional pressure difference receiver, which
      enhances the directional cues (mainly azimuth), and a computational mechanism in
      their auditory pathways to suppress echoes of redirected sound.

PMID- 15258639
TI  - Strategies that facilitate or counter eavesdropping on vocal interactions in
      songbirds.
AB  - Most territorial songbirds live in communication networks where eavesdropping on
      vocal interactions may constitute an important option for gathering information
      regarding the relative dominance, condition and quality of individuals being
      eavesdropped upon. The relatively low costs and risks of eavesdropping, together
      with the obvious advantages of gaining such comparative information about other
      individuals, predict eavesdropping to be a widespread phenomenon even though it
      is not necessarily advantageous for the participants to be eavesdropped upon.
      Special eavesdropper strategies that facilitate eavesdropping (how best to
      eavesdrop) may therefore have evolved together with strategies for interacting
      that either co-facilitate (public signaling) or counter eavesdropping directly
      (private signaling) or indirectly by preventing any subsequent negative
      consequences of being eavesdropped upon (anonymity). This paper reviews the
      predictions for the strategies and also gives examples supporting their use by
      territorial songbirds in connection with vocal interactions.

PMID- 15258640
TI  - Penguins and their noisy world.
AB  - Penguins identify their mate or chick by an acoustic signal, the display call.
      This identification is realized in a particularly constraining environment: the
      noisy world of a colony of thousands of birds. To fully understand how birds
      solve this problem of communication, we have done observations, acoustic
      analysis, propagation and playback experiments with 6 species of penguins studied
      in the field. According to our results, it appears that penguins use a
      particularly efficient "anti-confusion" and "anti-noise" coding system, allowing
      a quick identification and localization of individuals on the move in a noisy
      crowd.

PMID- 15258641
TI  - Tonal vocalizations in a noisy environment: an approach to their semi-automatic
      analysis and examples of its application.
AB  - Vocalizations with an emphasized fundamental are common in many species of
      animals. Such calls can presumably be sufficiently described by measures of their
      fundamental shape or 'contour'. Here we describe a software we developed to
      analyze such vocalizations semi-automatically. The software is particularly
      designed to cope with vocalizations recorded in a noisy environment. Some of the
      algorithms implemented (e.g. signal detection, contour detection, contour
      measurement, validation) and some preliminary applications dealing with calls of
      different species of birds are presented. Finally, we briefly discuss the
      possible significance of such vocalizations.

PMID- 15258642
TI  - Causes and consequences of song amplitude adjustment in a territorial bird: a
      case study in nightingales.
AB  - Vocal amplitude, one of the crucial factors for the exchange of acoustic signals,
      has been neglected in studies of animal communication, but recent studies on song
      variation in Common Nightingales Luscinia megarhynchos have revealed new insights
      into its importance in the singing behavior of territorial birds. In nightingales
      song amplitude is not maximized per se, but is individually regulated according
      to the level of masking background noise. Also, birds adjust their vocal
      intensity according to social variables, as in male-male interactions. Moreover,
      during such interactions, males exploited the directionality of their songs to
      broadcast them in the direction of the intended receivers ensuring the most
      effective signal transmission. Studies of the development of this typical long
      range signaling suggest that sound level is highly interrelated with overall
      developmental progression and learning, and thus should be viewed as an integral
      part of song ontogeny. I conclude that song amplitude is a dynamic feature of the
      avian signal system, which is individually regulated according to the ecological
      demands of signal transmission and the social context of communication.

PMID- 15258643
TI  - Evolution of acoustic communication in crickets: phylogeny of Eneopterinae
      reveals an adaptive radiation involving high-frequency calling (Orthoptera,
      Grylloidea, Eneopteridae).
AB  - Evolution of dominant frequencies in songs of Eneopterinae crickets was studied
      with respect to phylogeny. Two characters are optimized on the tree: the first
      describes the frequency resulting from the vibration of the harp (Fda), and the
      second is due to the vibration of other tegminal areas (Fdb). Fda was found to be
      relatively stable through the subfamily. Its low ancestral state is replaced by a
      high Fda only once, resulting in high-frequency calling in [Cardiodactylus
      (Lebinthus-Agnotecous)]. A high Fdb component is added to the low ancestral Fda
      in Eneoptera guyanensis, resulting in frequency modulation. The onset of high Fd
      in this first subclade is accompanied by a high cladogenesis rate, which supports
      a hypothesis of adaptive radiation for high frequencies. The effectiveness of
      high-frequency calling is discussed in relation to the species behavior ecology.

PMID- 15258644
TI  - Acoustic evolution in crickets: need for phylogenetic study and a reappraisal of
      signal effectiveness.
AB  - Cricket stridulums and calls are highly stereotyped, except those with greatly
      modified tegmina and/or venation, or "unusual" frequency, duration and/or
      intensity. This acoustic diversity remained unsuspected until recently, and
      current models of acoustic evolution in crickets erroneously consider this clade
      homogeneous for acoustic features. The few phylogenetic studies analyzing
      acoustic evolution in crickets demonstrated that acoustic behavior could be
      particularly labile in some clades. The ensuing pattern for cricket evolution is
      consequently extremely complex. We argue that: (1) phylogeny should always be
      considered when analyzing acoustic evolution, whatever characters are considered
      (signals, stridulums or behaviors). Consequently, future studies should be
      devoted to entire clades, and not consider isolated taxa; character and character
      state definitions should allow significant reconstructions of character
      evolutionary transformations; and homologies should be carefully defined for all
      characters, including behavior. (2) The factors responsible for song
      effectiveness should be reconsidered and hypotheses on their potential influence
      on signal evolution tested jointly by phylogenies (for example, to assess
      correlated transformations of acoustic and ecological features), and population
      studies (for example, to correlate call range and population structure, or test
      the predation risk associated with a signal structure). Better understanding
      these points should help clarifying acoustic evolution in crickets.

PMID- 15258645
TI  - Bioacoustic investigations and taxonomic considerations on the Cicadetta montana
      species complex (Homoptera: Cicadoidea: Tibicinidae).
AB  - Recent bioacoustic investigations have shown that Cicadetta montana Scopoli 1772
      is a complex of morphologically similar sister species that are best
      characterized by their song patterns. At the type locality of C. montana, only
      mountain cicadas with simple, long lasting song phrases were heard, recorded and
      collected. Therefore, we have good reasons to suggest that this type of song is
      characteristic for C. montana s. str. Boulard described a song of C. montana from
      France with phrases composed of a long and a short echeme; this type of song is
      characteristic for cicadas morphologically corresponding to C. montana var.
      brevipennis Fieber 1876; we suggest to raise this taxon to species level. On the
      basis of specific song, Puissant and Boulard described C. cerdaniensis from
      Pyrenees. A similar case was the discovery and description of C. montana
      macedonica Schedl 1999 from Macedonia; since these Macedonian cicadas are
      sympatric with at least two other cryptic species in the C. montana group and
      molecular investigations showed substantial genetic differences between C.
      macedonica and C. montana or C. brevipennis, we conclude that this taxon should
      also be raised to species level. Songs of closely related C. podolica and Korean
      mountain cicada are presented as well.

PMID- 15258646
TI  - Complex communication signals: the case of the Blue-black Grassquit Volatinia
      jacarina (Aves, Emberizidae) song. Part I--a structural analysis.
AB  - The song of the Blue-black Grassquit Volatinia jacarina is different for every
      individual and the structural differences between individuals are quite complex.
      Samples of songs from different Brazilian localities, as well as from Venezuela
      and Mexico, were studied through a comparative analysis of their sonograms. From
      the structural point of view, the results show a song composed of a single note
      that is compacted in a "window" between 2 and 13 kHz and rarely occupying more
      than half of a second. The note is essentially pure and is repeatedly uttered
      with a high level of fidelity. A global frequency modulation decreases from the
      beginning to the end of the song. The main song components are referred to as
      "Blocks" and are of three types: "Vibrations" (Buzzes or Vibratos), "Arabesques"
      (complex notes) and "Isolated Modulations" (simple syllables). Among other
      characteristics are double voices, which are quite diverse and probably function
      as codes for individual recognition. This song is considered a special case where
      a signature system has been developed to a high level of inter-individual
      variability.

PMID- 15258647
TI  - How a simple and stereotyped acoustic signal transmits individual information:
      the song of the White-browed Warbler Basileuterus leucoblepharus.
AB  - The White-browed Warbler Basileuterus leucoblepharus, a common bird of the
      BrazilianAtlantic forest, emits only one distinct song type in the context of
      territorial defense. Individual or neighbor-stranger recognition may be more
      difficult when birds share similar songs. In fact, the analysis of songs of
      different individuals reveals slight differences in the temporal and the
      frequency domains. Effectively, a careful examination of the signals of different
      individuals (21) by 5 complementary methods of analysis reveals first, that one
      or two gaps in frequency occur between two successive notes at different moments
      of the song, and second, that their temporal and frequency positions are
      stereotyped for each individual. Playback experiments confirm these findings. By
      propagation experiments, we show that this individual information can be only
      transmitted at short range (< 100 m) in the forest. In regard to the size and the
      repartition of territories, this communication process appears efficient and
      adaptive.

PMID- 15258648
TI  - Comparative analysis of the song of the Rufous-collared Sparrow Zonotrichia
      capensis (Emberizidae) between Campinas and Botucatu, Sao Paulo State, Brazil.
AB  - The regional dialects or regiolects of the Rufous-collared Sparrow Zonotrichia
      capensis were compared between Campinas (47 degrees 06'W-22 degrees 90'S) and
      Botucatu (48 degrees 44'W-22 degrees 88'S), Sao Paulo State, Southeastern Brazil.
      Songs of 88 individuals from thirteen localities were recorded. Sonograms showed
      that two areas presented more homogeneous songs, forming two regiolects. In 11
      localities most individuals shared the same song type. At the other two
      localities, they sang up to 5 different song types. This occurs at the boundaries
      of the regiolects, and was also where individuals singing more than one song type
      were found. Similarities between song types were not related to geographic
      distance between the respective singers. A comparative analysis showed
      similarities in these regiolects with song of populations from Northeastern
      Brazil.

PMID- 15258649
TI  - Acoustic communication in the Red-vented Bulbul Pycnonotus cafer.
AB  - This paper deals with acoustic communication in the Red-vented Bulbul Pycnonotus
      cafer. This species emits a high variety of vocal signals that can be classified
      on the basis of their acoustical features and context of production. Individuals
      sang throughout the year and most songs were discrete and stereotyped. The songs
      were composed of strophes (phrases) with minor structural variations of elements
      that were preceded and followed by a temporal gap (3 to 12 s). Most strophes were
      composed of 2 to 6 elements that were often dissimilar in structure and ranging
      from 0.98 to 4.5 kHz. The biological function of the song appeared to be to
      maintain pair bonds and to synchronize breeding activities. Different types of
      context-specific calls were identified. Individuals produced Type-I alarm calls
      (fast and wide-band, 1.03 to 6.36 kHz) under low predation pressure andType-II
      calls (narrow frequency range, 1.37 to 3.39 kHz) under high predation pressure.
      Roosting calls were fast and wide-band signals phonetically similar to Type-I
      alarm calls. Three types of begging/contact calls were recorded in
      nestlings/fledglings. Greeting calls and flight calls were composed of complex
      phrases, like song, but were short and used for proximate functions.

PMID- 15258650
TI  - Variation in the behavioral responses of Budgerigars Melopsittacus undulatus to
      an alarm call in relation to sex and season.
AB  - In the Budgerigar Melopsittacus undulatus, the significance of a conspecific
      alarm call was investigated in two seasons, winter and spring. Two qualitatively
      different behavioral responses were displayed by the receivers in reply to
      playbacks: call(s) and/or taking flight(s). The comparative analysis of the
      number of birds responding to the alarm and to the control signals revealed two
      major facts: 1) in both seasons, the responses to the alarm signal were only
      observed for females, not for males, 2) qualitatively, females exhibited a great
      inter-season variability in their behavioral responses to the hearing of an alarm
      call. In winter, the females were more predisposed to emit acoustic responses
      while in spring they mainly took flight.

PMID- 15258651
TI  - Modulation by steroid hormones of a "sexy" acoustic signal in an Oscine species,
      the Common Canary Serinus canaria.
AB  - The respective influence of testosterone and estradiol on the structure of the
      Common Canary Serinus canaria song was studied by experimentally controlling
      blood levels of steroid hormones in males and analyzing the consequent effects on
      acoustic parameters. A detailed acoustic analysis of the songs produced before
      and after hormonal manipulation revealed that testosterone and estradiol seem to
      control distinct song parameters independently. The presence of receptors for
      testosterone and estradiol in the brain neural pathway controlling song
      production strongly suggests that the observed effects are mediated by a steroid
      action at the neuronal level.

PMID- 15258652
TI  - Isolation induced changes in Guinea Pig Cavia porcellus pup distress whistles.
AB  - Guinea Pig Cavia porcellus pups emit high-pitched distress whistles when
      separated from their mother. In order to assess the influence of the duration of
      a brief isolation period on whistle acoustic structure, we recorded the distress
      whistles of six 8-day old pups separated for 15 min from their group in a novel
      environment and compared the mean values of the first and last 30 whistle notes.
      Acoustic analysis revealed, throughout the session, a significant decrease in
      whistle duration, an increase in mean frequency and a tendency for a decrease in
      number of harmonics in the first part of the note. Results demonstrate that,
      throughout a brief isolation period, the vocal response of Guinea Pig pups to
      isolation undergoes structural changes possibly related to time-dependent changes
      in motivational state.

PMID- 15258653
TI  - The song of the Brazilian population of Humpback Whale Megaptera novaeangliae, in
      the year 2000: individual song variations and possible implications.
AB  - The song of the Brazilian population of the Humpback Whale Megaptera novaeangliae
      was studied in its breeding and calving ground, the Abrolhos Bank, Bahia, Brazil,
      from July to November 2000. Aural and spectral analyses of digital recordings
      were completed for approximately 20 song cycles, totaling 5 hours of song from 10
      different recording events. We identified 24 note types, organized in five
      themes. All songs presented the same themes and the order in which they were sung
      did not vary. We registered the appearance of a note type and the disappearance
      of a phrase ending, which indicate that the song changed as the season
      progressed. Moreover, we detected individual variation in the way singers
      performed certain complex note types. As songs are transmitted culturally, it is
      likely that singers have different abilities to compose and/or learn new notes.
      If, as it has been previously suggested, 'new' songs are preferred to 'old' ones,
      these more able singers will be sending out information about their learning
      abilities that could be used by other whales to decide whether or not to interact
      with them.

PMID- 15258654
TI  - Analysis of whistles produced by the Tucuxi Dolphin Sotalia fluviatilis from
      Sepetiba Bay, Brazil.
AB  - From July 2001 to June 2002, we recorded a total of 2 h 55 min of Tucuxi Dolphin
      Sotalia fluviatilis vocalizations from Sepetiba Bay, Brazil (22 degrees 35'S-44
      degrees 03'W). A total of 3350 whistles were analyzed quantitative and
      qualitatively and were divided into 124 types, by visual inspection of sonograms.
      The following parameters were measured: Initial Frequency, Final Frequency,
      Minimum Frequency, Maximum Frequency, Duration, Number of Inflections, Frequency
      at the Inflection Points, Frequency at 1/2, 1/4, and 3/4 of whistle duration,
      Presence of Frequency Modulation and Harmonics. Ascending type whistles (N =
      2719) were most common, representing 82% of the total. Dolphin behavior and
      average group size observed during recording influenced the whistle's
      quantitative and qualitative parameters. The results demonstrate the great
      diversity of whistles emitted and indicate a functional role of these
      vocalizations during the observed behaviors.

PMID- 15258655
TI  - Differences in the whistle characteristics and repertoire of Bottlenose and
      Spinner Dolphins.
AB  - Several methods have been used to compare the whistles produced by dolphins. The
      two methods used in this study are: (1) a classification of whistle contours in
      six categories (i.e. constant frequency, upsweep, downsweep, concave, convex, and
      sine) and (2) the extraction of frequency and time parameters from each whistle
      contour. Bottlenose Dolphin Tursiops truncatus whistles are described in the same
      way when comparing whistle contour distributions in each of the six categories
      and whistle frequency and time parameters using Discriminant Function Analysis.
      For Spinner Dolphin Stenella longirostris whistles, each method describes
      whistles differently. Several facts may explain these differences in describing
      dolphin whistles, such as a greater fluidity of Spinner Dolphin groups when
      compared to Bottlenose Dolphin groups, greater geographic variation in the
      whistles of Bottlenose Dolphins than in those of Spinner Dolphins, an average
      beginning frequency 16% lower than the average ending frequency in Spinner
      Dolphin whistles compared to a varied relationship for Bottlenose Dolphins, and
      stricter criteria used to define whistle contour categories in the study of
      Spinner Dolphin whistles than in the Bottlenose Dolphin whistle study.

PMID- 15258656
TI  - Long-distance calls in Neotropical primates.
AB  - Long-distance calls are widespread among primates. Several studies concentrate on
      such calls in just one or in few species, while few studies have treated more
      general trends within the order. The common features that usually characterize
      these vocalizations are related to long-distance propagation of sounds. The
      proposed functions of primate long-distance calls can be divided into extragroup
      and intragroup ones. Extragroup functions relate to mate defense, mate attraction
      or resource defense, while intragroup functions involve group coordination or
      alarm. Among Neotropical primates, several species perform long-distance calls
      that seem more related to intragroup coordination, markedly in atelines.
      Callitrichids present long-distance calls that are employed both in intragroup
      coordination and intergroup contests or spacing. Examples of extragroup directed
      long-distance calls are the duets of titi monkeys and the roars and barks of
      howler monkeys. Considerable complexity and gradation exist in the long-distance
      call repertoires of some Neotropical primates, and female long-distance calls are
      probably more important in non-duetting species than usually thought. Future
      research must focus on larger trends in the evolution of primate long-distance
      calls, including the phylogeny of calling repertoires and the relationships
      between form and function in these signals.

PMID- 15258657
TI  - Vocal sequential exchanges and intragroup spacing in the Northern Muriqui
      Brachyteles arachnoides hypoxanthus.
AB  - Sequential exchanges of vocalizations (staccatos and neighs) emitted by Northern
      Muriquis Brachyteles arachnoides hypoxanthus were recorded at the Biological
      Station of Caratinga, Minas Gerais State, Brazil. Staccatos and neighs containing
      larger proportion of short elements were preferentially produced during short
      range exchanges; neighs, produced by a larger number of participants, were
      typical of long-range exchanges. Staccatos emitted by animals feeding in a
      dispersed manner contained a larger proportion of tonal elements than those
      emitted by muriquis feeding in a cohesive manner. Sequential exchanges seem thus
      to be constituted by two inter-related subsystems of calls that aid muriquis to
      coordinate intragroup spacing, despite the poor visibility of the habitat.

PMID- 15258658
TI  - Bioacoustics of human whistled languages: an alternative approach to the
      cognitive processes of language.
AB  - Whistled languages are a valuable heritage of human culture. This paper gives a
      first survey about a new multidisciplinary approach to these languages. Previous
      studies on whistled equivalents of languages have already documented that they
      can provide significant information about the role of rhythm and melody in
      language. To substantiate this, most whistles are represented by modulations of
      frequency, centered around 2000 Hz (+/- 1000 Hz) and often reach a loudness of
      about 130 dB (measured at 1m from the source). Their transmission range can reach
      up to 10 km (as verified in La Gomera, Canary Island), and the messages can
      remain understandable, even if the signal is deteriorated. In some cultures the
      use of whistled language is associated with some "talking musical instruments"
      (e.g. flutes, guitars, harps, gongs, drums, khens). Finally, whistles as a means
      of conveying information have some analogues in the animal kingdom (e.g. some
      birds, cetaceans, primates), providing opportunities to compare the acoustic
      characteristics of the respective signals. With such properties as a reference,
      the project reported here has two major tasks: to further elucidate the many
      facets of whistled language and, above all, help to immediately stop the process
      of its gradual disappearance.

PMID- 15258659
TI  - Communication by unvoiced speech: the role of whispering.
AB  - Most studies on whispering deal with its production and perception, neglecting
      its communicative role. I have focused on this, especially some social and
      psychobiological objectives. I have combined a general inquiry into the use of
      unvoiced speech with stimulus-response experiments on particular signal
      properties. (1) Analyses of answers to queries revealed that judgments about
      whispering depend on the social contexts. In the private domain it plays a
      clearly positive role, but in the public domain it is more problematical. Two
      causative factors were identified as relevant: (a) an 'ingroup' function of
      whispering which could induce negative 'outgroup' effects in co-listeners, and
      (b) a psychobiological component of whispering which could affect the auditory
      vigilance of co-listeners who were not addressed personally by the signaling, but
      often wanted to understand a whispered message. (2) Analyses of experimental data
      confirmed the relevance of these factors. Additionally, they showed that unvoiced
      speech has a limited transmission range, and is easily masked by background
      noise. Taken together, the results suggest that whispering is explained best as a
      close-distance signal adapted for private use among partners.

PMID- 15258660
TI  - Bits and q-bits as versatility measures.
AB  - Using Shannon information theory is a common strategy to measure any kind of
      variability in a signal or phenomenon. Some methods were developed to adapt
      information entropy measures to bird song data trying to emphasize its
      versatility aspect. This classical approach, using the concept of bit, produces
      interesting results. Now, the original idea developed in this paper is to use the
      quantum information theory and the quantum bit (q-bit) concept in order to
      provide a more complete vision of the experimental results.

PMID- 15258661
TI  - Species richness and relative abundance of birds in natural and anthropogenic
      fragments of Brazilian Atlantic forest.
AB  - Bird communities were studied in two types of fragmented habitat of Atlantic
      forest in the State of Parana, southern Brazil; one consisted of forest fragments
      that were created as a result of human activities (forest remnants), the other
      consisted of a set of naturally occurring forest fragments (forest patches).
      Using quantitative data obtained by the point counts method in 3 forest patches
      and 3 forest remnants during one year, species richness and relative abundance
      were compared in those habitats, considering species groups according to their
      general feeding habits. Insectivores, omnivores, and frugivores presented similar
      general tendencies in both habitats (decrease of species number with decreasing
      size and increasing isolation of forest fragment). However, these tendencies were
      different, when considering the relative abundance data: the trunk insectivores
      presented the highest value in the smallest patch while the lowest relative
      abundance was in the smallest remnant. In the naturally fragmented landscape,
      time permitted that the loss of some species of trunk insectivores be compensated
      for the increase in abundance of other species. In contrast, the remnants
      essentially represented newly formed islands that are not yet at equilibrium and
      where future species losses would make them similar to the patches.

PMID- 15258662
TI  - Automated bioacoustic identification of species.
AB  - Research into the automated identification of animals by bioacoustics is becoming
      more widespread mainly due to difficulties in carrying out manual surveys. This
      paper describes automated recognition of insects (Orthoptera) using time domain
      signal coding and artificial neural networks. Results of field recordings made in
      the UK in 2002 are presented which show that it is possible to accurately
      recognize 4 British Orthoptera species in natural conditions under high levels of
      interference. Work is under way to increase the number of species recognized.

PMID- 15258663
TI  - Identification of Tibicen cicada species by a Principal Components Analysis of
      their songs.
AB  - Specific identification of three Tibicen cicadas, T. japonicus, T. flammatus and
      T. bihamatus, by their chirping sounds was carried out using Principal Components
      Analysis (PCA). High quality recordings of each species were used as the
      standards. The peak and mean frequencies and the pulse rate were used as the
      variables. Out of 12 samples recorded in the fields one fell in the vicinity of
      T. japonicus and all other were positioned near T. bihamatus. Then the cluster
      analysis of the PCA scores clearly separated each species and allocated the
      samples in the same way.

PMID- 15258664
TI  - Application of automated bioacoustic identification in environmental education
      and assessment.
AB  - Developments in electronics and computer science have led to the introduction of
      an automated bioacoustic identification device used to resolve commonly
      encountered problems in the identification of animal species in the field. This
      technology aids our auditory observations, and also improves the quality of
      biological surveys and environmental monitoring. In this paper the future roles
      and possibilities of bioacoustics are discussed, providing some examples from the
      realm of environmental education and monitoring that focus on the use of nature
      sounds.

PMID- 15258665
TI  - Compact and user-friendly ultrasound acquisition systems optimized for field
      recording.
AB  - A compact and rugged hardware interface for laptop-based ultrasound recording in
      the field has been developed. The versatile devices overcome the limitations and
      drawbacks of previously available solutions. The accompanying recording software
      enables flexible hard disk recording for both manual and automated operation.

PMID- 15258666
TI  - Natural sound archives: past, present and future.
AB  - Recordings of wild animals were first made in the Palearctic in 1900, in the
      Nearctic in 1929, in Antarctica in 1934, in Asia in 1937, and in the Neotropics
      in the 1940s. However, systematic collecting did not begin until the 1950s.
      Collections of animal sound recordings serve many uses in education,
      entertainment, science and nature conservation. In recent years, technological
      developments have transformed the ways in which sounds can be sampled, stored and
      accessed. Now the largest collections between them hold altogether around 0.5
      million recordings with their associated data. The functioning of a major archive
      will be described with reference to the British Library Sound Archive. Preserving
      large collections for the long term is a primary concern in the digital age.
      While digitization and digital preservation has many advantages over analogue
      methods, the rate of technology change and lack of standardization are a serious
      problem for the world's major audio archives. Another challenge is to make
      collections more easily and widely accessible via electronic networks. On-line
      catalogues and access to the actual sounds via the internet are already available
      for some collections. Case studies describing the establishment and functioning
      of sound libraries in Mexico, Colombia and Brazil are given in individually
      authored sections in an Appendix.

PMID- 15258668
TI  - Testicular infarction and rupture after blunt trauma--use of diagnostic
      ultrasound.
AB  - We report the case of a 23-year-old male who suffered localised testicular
      infarction and rupture following blunt trauma. This pathology is rare after blunt
      trauma and has not been previously described in literature. The appearance on
      ultrasound resembled malignancy, necessitating orchidectomy. An overview of the
      pathology of testicular trauma as well as its management is given with particular
      emphasis on the use diagnostic ultrasound in testicular trauma.

PMID- 15258669
TI  - The physiology constant database of teen-agers in Beijing.
AB  - Physiology constants of adolescents are important to understand growing living
      systems and are a useful reference in clinical and epidemiological research.
      Until recently, physiology constants were not available in China and therefore
      most physiologists, physicians, and nutritionists had to use data from abroad for
      reference. However, the very difference between the Eastern and Western races
      casts doubt on the usefulness of overseas data. We have therefore created a
      database system to provide a repository for the storage of physiology constants
      of teen-agers in Beijing. The several thousands of pieces of data are now divided
      into hematological biochemistry, lung function, and cardiac function with all
      data manually checked before being transferred into the database. The database
      was accomplished through the development of a web interface, scripts, and a
      relational database. The physiology data were integrated into the relational
      database system to provide flexible facilities by using combinations of various
      terms and parameters. A web browser interface was designed for the users to
      facilitate their searching. The database is available on the web. The statistical
      table, scatter diagram, and histogram of the data are available for both anonym
      and user according to queries, while only the user can achieve detail, including
      download data and advanced search.

PMID- 15258670
TI  - Physical fitness and functional ability of children with intellectual disability:
      effects of a short-term daily treadmill intervention.
AB  - Persons with intellectual disability (ID) and associated multiple disabilities
      have been found by many researchers to be a population with deficient physical
      fitness measures, which can be explained by an inactive lifestyle, a result of
      lack of awareness of the positive physical effects of physical exercise, or lack
      of motivation for any motor activity. Various plans for physical exercise have
      been put forward, but many are found impractical in nonresearch-based
      intervention. In this study, 15 children with ID on a motor functioning level of
      7-14 months used a treadmill daily for 2 months. Our findings indicated a most
      significant improvement in the level of physical fitness of the participants (p <
      0.005), as measured by pulse at rest and during effort. The improvement in
      physical fitness modestly (r = 0.5), but significantly (p < 0.05), correlated
      with a significant (p < 0.0007) improvement in functional ability of the
      participating children. Further examination a year after intervention terminated
      showed a return to preintervention pulse-at-rest values. The research examined
      the treadmill training method and found that it can be operated with the support
      of an unskilled staff person under the supervision of a physiotherapist. The
      research was performed under real-life conditions, enabling relatively easy
      implementation in the existing conditions of special education centers. This
      method is a type of exercise that is easy to operate without entailing long-term
      budgetary expenses and might improve the health status of children with ID, who
      are a population at risk for developing heart-related diseases at a young age.

PMID- 15258671
TI  - Primary infertility and azoospermia due to congenital bilateral absent vas
      deferens in the presence of a solitary kidney.

PMID- 15258672
TI  - Plutonium in the arctic marine environment--a short review.
AB  - Anthropogenic plutonium has been introduced into the environment over the past 50
      years as the result of the detonation of nuclear weapons and operational releases
      from the nuclear industry. In the Arctic environment, the main source of
      plutonium is from atmospheric weapons testing, which has resulted in a relatively
      uniform, underlying global distribution of plutonium. Previous studies of
      plutonium in the Kara Sea have shown that, at certain sites, other releases have
      given rise to enhanced local concentrations. Since different plutonium sources
      are characterised by distinctive plutonium-isotope ratios, evidence of a
      localised influence can be supported by clear perturbations in the plutonium
      isotope ratio fingerprints as compared to the known ratio in global fallout. In
      Kara Sea sites, such perturbations have been observed as a result of underwater
      weapons tests at Chernaya Bay, dumped radioactive waste in Novaya Zemlya, and
      terrestrial runoff from the Ob and Yenisey Rivers. Measurement of the plutonium
      isotope ratios offers both a means of identifying the origin of radionuclide
      contamination and the influence of the various nuclear installations on inputs to
      the Arctic, as well as a potential method for following the movement of water and
      sediment loads in the rivers.

PMID- 15258674
TI  - Philosophy of science: how to identify the potential research for the day after
      tomorrow?
AB  - We were asked to participate in a workshop to assist the European Commission on
      how to choose financial support for high-potential, basic research projects that
      can give new scientific breakthroughs and thus contribute significantly to the
      positive development of society, industry, and economy for the day after
      tomorrow. At this workshop, we analyzed the problem in some detail using
      experience from our own research on the global quality of life. We would suggest
      that the most promising projects have the following characteristics: (1) they are
      led by a brilliant researcher who considers his/her research to be "sweet
      science", who wants to explain the anomalies of his/her field of science, and who
      lives in a nonmainstream scientific paradigm; (2) they are deeply engaged in the
      philosophical problems of their research field, they are searching eagerly for a
      new understanding and a new theory, giving new tools for measurement and creating
      change, and results are taken as feedback on all levels from tool to theory and
      philosophy; (3) they are focused on the key point(s), which is an essential
      feature of the universe that creates global change if intervened upon. At the
      NEST Pathfinder 2005 Topic Identification Workshop, Brussels 28 May 2004 entitled
      "Measuring the Impossible", we advised the European Commission Research
      Directorate to allocate funds for projects focusing on the state of consciousness
      -how to understand it, how to map it, and how to develop it.

PMID- 15258675
TI  - Antioxidant capacity of cultured mammalian cells estimated by ESR method.
AB  - In the present study, the antioxidant capacity against hydrogen peroxide (H2O2),
      one of the stress-inducing agents, was investigated in two distinct cell lines: L
      41 (human epithelial-like cells) and HLF (human diploid lung fibroblasts), which
      differ in tissue origin, life span in culture, proliferate activity, and special
      enzyme system activity. The cell antioxidant capacity against H2O2 was estimated
      by the electron spin resonance (ESR) spin-trapping technique in the Fenton
      reaction system via Fe+2 ion action with H2O2 resulting in hydroxyl radical
      generation. The effects of catalase inhibitors, such as sodium azide and 3-amino
      1,2,4-triazole, on the antioxidant capacity of cells were tested. Based on our
      observation, it can be concluded that the defensive capacity of cells against
      H2O2 depends on the ratio between catalase/GPx/SOD and H2O2, especially at high
      stress situations, and the intracellular balance of these enzymes are more
      important than the influence of the single component.

PMID- 15258676
TI  - Snoezelen: children with intellectual disability and working with the whole
      family.
AB  - Snoezelen, or controlled multisensory stimulation, was first introduced in Israel
      in 1993. This paper presents a new concept of working with the whole family in
      the Snoezelen room with the participation of a social worker. The purpose was to
      facilitate family encounters with the child, to enable parents and siblings to
      become better acquainted with the resident through his/her strengths and special
      abilities, to encourage parental involvement in the care, to encourage increased
      visits, to improve quality of life (QOL) for the resident, and to reinforce a
      better relationship between resident, family, and home. Sessions were divided
      into two major parts. The first segment (duration 20-40 min) was free activity
      and the second was more structured (duration 15-30 min). Case stories are
      presented to illustrate the positive effects of this approach. Snoezelen can be
      used with the entire family with the participation of a social worker and can add
      new dimensions to communication.

PMID- 15258677
TI  - Clinical profiles, occurrence, and management of adolescent patients with HAIR-AN
      syndrome.
AB  - The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans
      (HAIR-AN) is a subphenotype of the polycystic ovary syndrome. It is one of the
      most common causes of menstrual problems, hyperandrogenic symptoms, and insulin
      resistance among young women. Review of clinical data in an outpatient adolescent
      clinic showed that of the 1,002 young women (ages 10-21 years) attending the
      clinic over a 2-year period, 50 (5%) were diagnosed with HAIR-AN syndrome. Mean
      age of the patients was 15.5, initial mean weight at diagnosis was 94.5 kg, and
      the mean BMI was 33.33 kg/m2. Patients were treated with a weight-stabilization
      and -reduction program, oral contraceptive pills, and in most cases metformin. Of
      the patients, 80% were compliant with the follow-up and treatment regimen, 60%
      maintained or reduced their weight, 95% had regular menstrual cycles, and in most
      patients, the acne and/or hirsutism were the same or better than at the start of
      treatment. We conclude that HAIR-AN syndrome is a common disease in young women
      and multifaceted, aggressive treatment appears to be effective in reducing the
      severity of symptoms and preventing further consequences.

PMID- 15258678
TI  - Long-term evaluation of the use of the transdermal contraceptive patch in
      adolescents.
AB  - The transdermal contraceptive patch, Ortho Evra, was approved in December 2001
      and released on the market in June 2002. In this study, we reviewed clinical data
      of young women who started the patch between June 2002 and December 2003 in the
      adolescent medicine clinic at a university-based outpatient center. A total of 62
      patients started the patch in that period and two of them were lost to follow-up.
      Mean age of patients was 17.9 years and mean length of use was 10 cycles. Only 10
      patients (16.7%) discontinued use. Reasons for discontinuation were moderate to
      severe skin irritation (3 patients, 5%), complete detachment (3 patients, 5%),
      and economic reasons (4 patients, 6.7%). Compliance was excellent overall and the
      side-effects profile was good. No pregnancies occurred during this period. These
      results confirmed that the transdermal contraceptive patch is easy to use and an
      effective method of birth control that may be better tolerated by young women. It
      also seemed to improve contraceptive compliance in this population.

PMID- 15258680
TI  - The relationship between lower extremity functional strength and severity of
      peripheral arterial disease.
AB  - The purposes of this study were to (1) determine if peripheral arterial disease
      (PAD) severity is related to deficits in lower extremity functional strength, (2)
      identify covariates that might affect the relationship between lower extremity
      functional strength and severity of PAD, and (3) determine if the relationship
      between lower extremity functional strength and severity of PAD still persists
      after statistically controlling for significant covariates. A total of 144
      patients were grouped into tertiles according to disease severity. Patients
      having an ankle-brachial index (ABI) of 0.76 to 0.90 were classified as having
      mild PAD (high ABI group), 0.51 to 0.75 classified as having moderate PAD
      (moderate ABI group), and 0.36 to 0.50 as having severe PAD (low ABI group).
      Lower extremity functional strength was assessed using the chair-stand test where
      the time to complete 5 consecutive stand-to-sit transfers was recorded. Patients
      were also characterized on ambulatory function and clinical characteristics. The
      moderate ABI group took significantly (p < 0.05) less time (13.49 +/- 0.49 s) to
      complete the chair-stand test than the low ABI group (15.86 +/- 0.63 s). Both
      daily physical activity level and total 6-minute walk distance were identified as
      significant covariates (p < 0.05) of lower extremity functional strength. After
      controlling for daily physical activity level and total 6-minute walk distance,
      no significant differences (p > 0.05) in the time to complete the chair-stand
      test existed between the ABI groups. These findings indicate that the greater
      impairment in lower extremity functional strength in patients with severe PAD is
      explained by their lower physical activity level and poorer overall walking
      ability.

PMID- 15258681
TI  - Anticardiolipin antibodies as a risk factor of atherosclerosis in intermittent
      claudication.
AB  - Anticardiolipin antibodies have been associated as a risk factor of
      atherosclerosis. The aim of this study was to evaluate the association between
      anticardiolipin antibodies and intermittent claudication. Forty consecutive
      patients (33 men, 7 women; age range: 45-84 years, mean 65.5) who were seen in
      the angiology and vascular surgery department with intermittent claudication were
      evaluated. Exclusion criteria included prior revascularization, angioplasty, or a
      history of thrombosis of a lower limb. Forty individuals (23 men, 17 women; age
      range: 58-82 years, mean 67.1) who attended a support group for senior citizens
      and who were apparently healthy formed the control group. Anticardiolipin
      antibodies were evaluated by means of enzyme-linked immunosorbent assay (ELISA)
      for quantitative measurement of immunoglobulin G (IgG) and IgM antibodies against
      cardiolipins in serum. IgG levels were considered normal when < 7, borderline
      from 7 to 10, and elevated at > 10 GPL units/mL; IgM levels were normal when < 4,
      borderline from 4 to 7, and elevated at > 7 MPL, as recommended by the test
      manufacturers. Statistical analysis used the relative risk test with a confidence
      interval of 95%. Twenty-three patients from the study group and 6 individuals
      from the control group were found to have elevated levels of anticardiolipin
      antibodies giving a relative risk of 3.833 (ranging from 1.749 to 8.4; p value <
      0.0001). In conclusion, patients who have elevated levels of anticardiolipin
      antibodies present a 3.8 times greater risk of developing intermittent
      claudication.

PMID- 15258682
TI  - Effects of policosanol and ticlopidine in patients with intermittent
      claudication: a double-blinded pilot comparative study.
AB  - Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects.
      The present study was undertaken to compare the effects of policosanol and
      ticlopidine in patients with moderately severe intermittent claudication (IC).
      The study had a 4-week baseline step, followed by a 20-week double-blinded,
      randomized treatment period. Twenty-eight eligible patients were randomized to
      policosanol 10 mg or ticlopidine 250 mg tablets twice daily (bid). Walking
      distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature
      25 degrees C) were assessed before and after 20 weeks of treatment. Both groups
      were similar at baseline. Compared with baseline, policosanol significantly
      increased (p < 0.01) mean values of initial (ICD) and absolute (ACD) claudication
      distances from 162.1 to 273.2 m and from 255.8 to 401.0 m, respectively.
      Ticlopidine also raised significantly (p < 0.01) ICD (166.2 to 266.3 m) and ACD
      (252.9 to 386.4 m). Comparisons between groups did not show significant
      differences. Policosanol, but not ticlopidine, significantly (p < 0.05), but
      modestly, increased the ankle/arm pressure ratio. After 10 weeks, policosanol
      significantly (p < 0.001) lowered low-density lipoprotein-cholesterol (LDL-C),
      total cholesterol (TC) (p < 0.01), and TC/HDL-C and raised (p < 0.05) high
      density lipoprotein-cholesterol (HDL-C). At study completion, policosanol lowered
      (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased (p < 0.01)
      HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the
      lipid profile variable. Policosanol induced modest, but significant, reductions
      (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine.
      Treatments were well tolerated and did not impair safety indicators. Three
      ticlopidine patients (21.4%) withdrew from the trial, only 1 owing to a serious
      adverse experience (AE) (unstable angina). Three other ticlopidine patients
      experienced mild AE (headache, diarrhea, and acidity). It is concluded that
      policosanol (10 mg bid) can be as effective as ticlopidine (250 mg bid) for
      improving walking distances of claudicant patients, and it could be advantageous
      for the global risk of these individuals owing to its cholesterol-lowering
      effects. This study is, however, just a pilot comparison, so that further studies
      in larger sample sizes are needed for definitive conclusions of the comparative
      effects of both drugs on patients with IC.

PMID- 15258683
TI  - Reproductive history in women with lower limb ischemia.
AB  - The purpose of this study was to identify reproductive factors that may
      contribute to the development of arteriosclerosis in the leg arteries by
      comparing the reproductive history of women with lower limb ischemia to a
      reference group of women. All 173 female patients treated for chronic lower limb
      ischemia with surgical or endovascular procedures performed from 1994 to 1996 at
      a university clinic received a validated questionnaire to which 116 (67%)
      responded. The reference group, 348 women, 197 (57%) of whom responded, was
      recruited randomly from the hospital catchment area. The 2 groups were similar
      regarding age at menopause and menarche, pregnancies, salpingo-oophorectomies,
      and hormone replacement therapy. There was a higher number of women who had used
      oral contraceptives in the reference group than in the patient group (53% vs 16%,
      p < 0.001). The same results were found when comparing the subgroup of patients
      younger than 55 years to the references. No association between reproductive
      history and development of lower limb ischemia could be found. Our results
      support that use of oral contraceptives early in life is not associated with an
      increased risk for lower limb ischemia.

PMID- 15258684
TI  - Hypothesis: a potential role for the vasa vasorum in the maintenance of vein
      graft patency.
AB  - Autologous saphenous vein is the most commonly used conduit for coronary artery
      bypass surgery with more than 50% grafts occluding within 10 years. In
      conventional preparation the vein undergoes considerable surgical trauma with
      damage to the outer layers during harvesting. Within these regions are situated
      the vasa vasorum and small vessels providing oxygen and nutrients to the vessel
      wall. Certain vasa vasorum terminate in the vessel lumen where it is suggested
      that they have a physiological role. Preservation of the vasa vasorum of
      saphenous veins used as bypass conduits may play an important role in the
      maintenance of graft patency.

PMID- 15258685
TI  - Cigarette smoking increases plasma concentrations of vascular cell adhesion
      molecule-1 in patients with coronary artery disease.
AB  - Cigarette smoking adversely affects endothelial function and increases risk of
      coronary artery disease (CAD). The pathogenesis of coronary atherosclerosis is
      currently thought to involve interactions between inflammatory cells and vascular
      endothelium. Adhesion molecules play a pivotal role in the accumulation of
      inflammatory cells at the endothelium. Little is known about the role of
      cigarette smoking in this atherosclerotic inflammatory process. The aim of this
      study was to evaluate the effects of cigarette smoking on the plasma
      concentrations of soluble vascular cell adhesion molecule-1 (VCAM-1) in patients
      with CAD. The soluble VCAM-1 level was quantified in smoking CAD patients (n =
      19) in comparison to those from patients with CAD alone (n = 10). Plasma
      concentrations of soluble VCAM-1 were measured by enzyme-linked immunosorbent
      assay. The soluble VCAM-1 level was found significantly higher in smokers than in
      nonsmokers (32.1279 +/- 21.6421 vs 9.4570 +/- 7.8138 ng/mL, p < 0.01), and in
      patients with previous myocardial infarction (MI) than in those without previous
      MI, but not significant statistically (27.7279 +/- 22.8813 vs 17.8170 +/- 15.9172
      ng/mL, p > 0.05). No significant difference was observed for soluble VCAM-1
      levels between hypertensive and nonhypertensive patients, multivessel and one
      vessel disease, or anterior and inferior MI localizations. The present study
      suggests that in patients with CAD, smoking leads to elevated levels of soluble
      VCAM-1 that may clarify one of the mechanisms of its accelerating effect on the
      atherosclerotic process.

PMID- 15258686
TI  - Frequency of provoked coronary spasms in patients undergoing coronary
      arteriography using a spasm provocation test via intracoronary administration of
      ergonovine.
AB  - There are no data concerning the incidence of provoked coronary arterial spasms
      via intracoronary administration of ergonovine (ER). This study sought to
      establish the incidence of spasms due to intracoronary injection of ER in
      Japanese patients who underwent coronary angiography. The subjects were 596
      consecutive patients (369 men, mean age 64.2 +/- 10.3 years) who were studied
      with a selective ER test. ER was administered in total doses of 40 microg into
      the right coronary artery and 64 microg into the left coronary artery. A positive
      spasm was defined as a total or subtotal occlusion. Coronary vasospasms were
      determined in 173 patients (29.0%). Spasms occurred often in patients with
      ischemic heart disease (43.3%); during effort and rest in patients with angina
      (46.3%), exertional angina (27.7%), recent myocardial infarction (36.7%), healed
      myocardial infarction (34.1%), and especially in patients with rest angina
      (55.5%), but were relatively uncommon in patients with nonischemic heart disease
      (3.7%). The incidence of provoked coronary spasms in this study was 2.2-2.6 times
      higher than in previous reports with intravenous ER administration. More spasms
      were superimposed on significant atherosclerotic lesions than on nonfixed
      atherosclerotic lesions (42.8% vs 24.0%, p < 0.01). No serious or irreversible
      complications were observed in this study. In conclusion, intracoronary
      administration of ER was a safe and reliable test. Compared with Caucasian
      patients, in Japanese patients, coronary arterial spasms occurred 2-3 times more
      frequently with various cardiac disorders.

PMID- 15258687
TI  - Intima-media thickness and arterial distensibility in Behcet's disease.
AB  - The etiology of Behcet's disease, a systemic vasculitis, is unknown. Vascular
      involvement may be seen in 25% of patients with Behcet's disease. Vasculitis make
      the prognosis of Behcet's disease severe. The aim of this study is to examine the
      structural and functional changes and relations of these changes with progression
      and prognosis of Behcet's disease. For this purpose, 40 patients with Behcet's
      disease and 40 healthy volunteer control subjects were analyzed, additionally
      patients with Behcet's disease were divided into 2 subgroups as those with
      vascular complications and those without vascular complications. Intima-media
      thickness and arterial distensibility were measured in all subjects with carotid
      artery ultrasonography. Carotid artery distensibility was significantly lower in
      the patient group compared to the control group (0.67 +/- 0.2, 0.93 +/- 0.4, p <
      0.05), and carotid artery IMT was significantly higher (0.59 +/- 12, 0.80 +/-
      0.11, p < 0.05). A statistically significant increase in IMT has been detected
      (0.77 +/- 11, 0.86 +/- 11, p < 0.05) in patients with Behcet's disease with
      vascular involvement compared to patients with Behcet's disease without vascular
      involvement, arterial distensibility in patients with vascular disease was
      similar with those who has no vascular disease (0.69 +/- 0.25, 0.63 +/- 0.25, p >
      0.05). There was a significant negative linear regression between arterial
      distensibility and systolic blood pressure (SBP) (B = -1 x 10(-2), p < 0.05), and
      a significant positive linear regression has also been found between IMT and SBP
      and diastolic blood pressure (DBP) and pulse pressure (PP) (B = 6.8 x 10(-3) for
      SBP, p < 0.05, B = 6.9 x 10(-3) for DBP, p < 0.05, B = 6 x 10(-3) for PP, p <
      0.05). As a result, IMT increases and AD decreases in patients with Behcet's
      disease compared to results in the control group. Although more studies are
      required for this subject, use of noninvasive parameters such as IMT and AD,
      which reflect the structural and functional characteristics of vasculature, may
      be useful to define disease progression and subjects at high risk.

PMID- 15258688
TI  - Antiphospholipid syndrome in Greece: clinical and immunological study and review
      of the literature.
AB  - The aim of this paper is to analyze the epidemiologic, clinical, and immunologic
      characteristics of the antiphospholipid syndrome (APS), primary or secondary, in
      autoimmune patients from Northern Greece. Sixty-seven patients with APS were
      included (9 men, 13.4%, and 58 women, 86.6%). Fifty-two (77.6%) patients had
      secondary APS and 15 had primary APS (22.4%). The mean age was 46.0 +/- 15.4
      years and the mean follow-up period was 62.7 +/- 15.0 months. Medical records
      were retrospectively analyzed from January 1994 until December 2001, according to
      a preestablished protocol. Eight patients (11.9%) had arterial thrombosis, 12
      (17.9%) had vein thrombosis, 12 (17.9%) had thrombocytopenia, 20 (29.8%) had
      neurologic disorders, and 51.6% of the women in reproductive age had, at least 2
      fetal losses (higher frequency in primary APS). Thirty-six patients (53.7%) had
      increased levels of both immunoglobulin G (IgG) and IgM anticardiolipin
      antibodies (ACA), 19 (28.4%) had IgG ACA only, and 12 (17.7%) had IgM ACA only.
      Antinuclear antibodies (ANA) were detected in 46 (68.6%) patients, and
      antineutrophil cytoplasmic antibodies (ANCA) in 29 (43.3%). All patients were
      prophylactically treated with aspirin (50-100 mg/day) and low-molecular-weight
      heparin and/or intravenous immunoglobulins-IVIGs occasionally (pregnant women).
      The findings of this study are, generally, similar to those described by others.
      Miscarriages seem to be more frequent in women with primary APS (p < 0.05),
      compared to other studies. Differences between these findings and those described
      by others concerning epidemiologic, clinical, or immunologic data are discussed.

PMID- 15258689
TI  - Tuberculous pericardial effusion: features, tamponade, and computed tomography.
AB  - The clinical features with particular reference to tamponade and mediastinal
      adenopathy were studied in tuberculous pericardial effusion. Tamponade is a
      frequent complication and the recognition of tuberculous etiology can be
      difficult. Involvement of the pericardium is mostly from mediastinal lymph nodes
      that have not been studied. This was a prospective cohort study. All patients had
      large effusions, and underwent pericardiocentesis and chest computed tomography.
      Patients with tuberculosis had specific therapy. Others with viral/idiopathic
      effusion served as controls for the computed tomography studies. There were 26
      patients with tuberculosis: 18 had tamponade on echocardiography. All had
      symptoms. Fever (n = 23) and dyspnea (n = 20) were the most frequent presenting
      symptoms. Pericardial rub was heard in 14, and 3 had enlarged cervical or
      axillary nodes. Pulmonary tuberculosis was present in 6. Tuberculin skin test
      measured 17 +/- 3.3 mm. The biopsy specimen showed a granuloma in 22 of 24. All
      26 had mediastinal lymph nodes > 10 mm with a mean size of 19.5 +/- 8.6 mm that
      disappeared (81%) or regressed (19%) on treatment (p < 0.001). Aortopulmonary
      nodes were most frequently enlarged (65.4%) and hilar the least. Three required
      pericardiectomy. At follow-up all were doing well. None with viral/idiopathic
      effusion had lymph node enlargement. Fever, dyspnea, and tamponade were frequent
      with tuberculosis. The prognosis was good with specific therapy. Mediastinal
      nodes were enlarged in all and only with tuberculosis and not with
      viral/idiopathic effusion. Nodes disappeared or regressed with treatment. In the
      appropriate clinical context, mediastinal lymph node enlargement on chest
      computed tomography along with a strongly positive skin test results could help
      in the diagnosis of a tuberculous etiology of pericardial effusion.

PMID- 15258690
TI  - Acute diastolic dysfunction due to pneumomediastinum following positive end
      expiratory pressure--a case report.
AB  - A 78-year-old woman was admitted for pulmonary embolism requiring orotracheal
      intubation and positive end-expiratory pressure. The pulmonary angiography
      confirmed a massive pulmonary embolism as suggested by echocardiography. Heparin
      and recombinant tissue plasminogen activator were successfully administrated;
      nevertheless, cardiogenic shock developed. A diastolic morphology of the right
      left cardiac pressures, despite a normalization of lung vasculature, was
      discovered by a repeated cardiac catheterization and pulmonary angiography. No
      tamponade was detected by echocardiography. Computed tomography demonstrated a
      large pneumomediastinum caused by positive end-expiration pressure, as a cause of
      the acute diastolic dysfunction. The patient died of a cardiac arrest after an
      unsuccessful drainage attempt.

PMID- 15258691
TI  - Cardiac displacement with a congenital complete left-sided pericardial defect in
      a patient with exertional angina pectoris--a case report.
AB  - A 71-year-old man with exertional chest pain was admitted to the hospital. A
      chest roentgenogram exhibited levoposition of the heart. An electrocardiogram
      showed clockwise rotation in the precordial leads and ST depression in V6, V7,
      V8, and V9 as well as in II, III, aVF leads associated with chest pain in a
      treadmill exercise test. The congenital complete left-sided pericardial defect
      could not be diagnosed preoperatively, but it was confirmed by thoracotomy.

PMID- 15258692
TI  - Reversible atrial lead dysfunction of DDD pacemaker after recent inferior
      myocardial infarction--a case report.
AB  - A patient with DDD pacemaker had pacing dysfunction following an inferior
      myocardial infarction. The threshold of that implanted right atrial pacing lead
      was abnormally high but the generator was normal. A temporary lead was inserted
      into the high right atrium near the appendage and near the low atrium for testing
      of threshold, which was abnormally high in these 2 places. Forty days after stent
      implantation in the proximal segment of the right coronary artery, the threshold
      spontaneously returned to normal. The change threshold of electrode-tissue
      interface in the right atrium was suspected due to hibernation of right atrium
      ischemia.

PMID- 15258693
TI  - Permanent myocardial dysfunction caused by high-voltage electrical injury--a case
      report.
AB  - Electrical injury, particularly alternating current, may lead to disease of
      conducting tissue or to myocardial damage, or even may cause sudden death. In the
      present case, the authors report a 22-year-old man who sustained extensive upper
      extremity trauma from a high-voltage electrical injury and manifested clinical
      signs of left ventricular heart failure.

PMID- 15258694
TI  - Pseudo-lesion of internal mammary artery graft and left anterior descending
      artery during percutaneous transluminal angioplasty--a case report.
AB  - New lesions appearing during coronary angioplasty may be due to spasms,
      dissection, and thrombosis. Straightening of the tortuous vessels by guidewire
      may produce transient angiographic pseudo-lesions, which mimic severe artery
      damage. An additional case is reported, in which simultaneous artifactual lesions
      involved the internal mammary artery and the left anterior descending coronary
      artery, mimicking thrombosis and dissection. Recognition of this entity is
      essential to avoid unnecessary interventions and potentially harmful
      complications.

PMID- 15258695
TI  - Inferior vena cava filter ensnarement by central line guide wires--a report of 4
      cases and brief review.
AB  - Ensnarement of inferior vena cava filters with central line guide wires is an
      infrequent complication that has been sporadically reported. The authors present
      4 patients who experienced this complication. They review the literature, make
      recommendations to avoid this preventable complication, and recommend what to do
      once the complication occurs.

PMID- 15258696
TI  - Differential gene expression during pre-symbiotic interaction between Tuber
      borchii Vittad. and Tilia americana L.
AB  - Ectomycorrhizal formation is a highly regulated process involving the molecular
      reorganization of both partners during symbiosis. An analogous molecular process
      also occurs during the pre-symbiotic phase, when the partners exchange molecular
      signals in order to position and prepare both organisms for the establishment of
      symbiosis. To gain insight into genetic reorganization in Tuber borchii during
      its interaction with its symbiotic partner Tilia americana, we set up a culture
      system in which the mycelium interacts with the plant, even though there is no
      actual physical contact between the two organisms. The selected strategies,
      suppressive subtractive hybridisation and reverse Northern blots, allowed us to
      identify, for the first time, 58 cDNA clones differentially expressed in the pre
      symbiotic phase. Sequence analysis of the expressed sequence tags showed that the
      expressed genes are involved in several biochemical pathways: secretion and
      apical growth, cellular detoxification, general metabolism and both mutualistic
      and symbiotic features.

PMID- 15258697
TI  - Chemosensitivity and radiosensitivity profiles of four new human epithelial
      ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFbeta-RII,
      KRAS2, TP53 and/or CDNK2A.
AB  - To address the cellular basis for the response to ovarian cancer treatment, we
      characterized the chemosensitivity and radiosensitivity of four human epithelial
      ovarian cancer cell lines that harbor different genetic alterations. The TOV-21G,
      TOV-81D, OV-90, and TOV-112D cell lines were derived from ovarian tumors (TOV) or
      ascites (OV) from chemotherapy- and radiotherapy-naive patients and were
      characterized by their mutation spectrum of BRCA2, TGFbeta-RII, KRAS2, TP53, and
      CDKN2A. Cells were monitored for survival following exposure at various
      concentrations to different cytotoxic agents including cisplatin, camptothecin or
      paclitaxel or to different doses of gamma-irradiation. At the lowest doses, the
      TGFbeta-RII-mutated and KRAS2-mutated cell line, TOV-21G, and the BRCA2-mutated
      cell line, TOV-81D, demonstrated a significantly higher sensitivity to cisplatin
      and gamma-irradiation than the TP53-mutated cell lines, TOV-112D and OV-90. At
      higher doses, differences between the TP53-mutated lines were observed with TOV
      112D being less sensitive to cisplatin than OV-90 that also harbors a CDNK2A
      mutation. All cell lines were similarly sensitive to high doses of gamma
      irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not
      significantly different between all cell lines, irrespective of the mutation
      status of BRCA1, BRCA2, TGFbeta-RII, KRAS2, TP53, and CDKN2A. The observed
      responses to treatment are consistent with the current knowledge concerning
      BRCA2, TGFbeta-RII, KRAS2, TP53, and/or CDKN2A aberrant function.

PMID- 15258698
TI  - Pharmacokinetics of platinum after oral or intravenous cisplatin: a phase 1 study
      in 32 adult patients.
AB  - AIMS: To develop a population pharmacokinetic model for simultaneous analysis of
      oral/intravenous cisplatin data in order to estimate the mean population
      pharmacokinetic parameters, mainly the bioavailability, of cisplatin and to
      evaluate the influence of covariates on the pharmacokinetic variability. METHODS:
      Pharmacokinetic and demographic data were collected from 32 adult patients (20
      males/12 females, age range 47-76 years) receiving 30-min infusions or an oral
      formulation of cisplatin, 10-30 mg/m2, for various malignancies. Both total
      plasma and ultrafilterable or unbound platinum concentrations were determined.
      RESULTS: Unbound and total platinum concentrations were ascribed to a two
      compartment model, with first-order absorption and elimination. The oral
      bioavailability (F) population estimates were, respectively, 0.39 and 0.30 with
      associated intersubject variabilities (ISV) of 24% and 26%. Peak concentrations
      following oral dosing occurred at 1.0 h and 1.6 h for unbound and total platinum,
      respectively. Clearance (CL) and central distribution volume (V1) of unbound
      platinum were significantly related to body surface area (BSA). The CL and V1
      mean estimates were, respectively, 37 l/h and 23 l with an associated ISV of 15%.
      The final pharmacokinetic models were validated using 1000 bootstrap samples of
      the original datasets. CONCLUSIONS: Both unbound and total platinum data allowed
      a fair evaluation of oral cisplatin disposition, with close estimations for both
      absorption rates and oral bioavailability. These results also support the
      conventional dose adjustment of cisplatin based on BSA.

PMID- 15258700
TI  - Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of [18F]fluorodeoxy
      D-glucose positron emission tomography (FDG-PET) on the primary staging of
      patients with small-cell lung cancer (SCLC). METHODS: FDG-PET was performed in
      120 consecutive patients with SCLC during primary staging. In addition, brain
      examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or
      computed tomography (CT) were performed in 91 patients. Results of FDG-PET were
      compared with those of conventional staging procedures. FDG-PET detected markedly
      increased FDG uptake in the primary tumours of all 120 patients (sensitivity
      100%). RESULTS: Complete agreement between FDG-PET results and other staging
      procedures was observed in 75 patients. Differences occurred in 45 patients at 65
      sites. In 47 sites the FDG-PET results were proven to be correct, and in ten,
      incorrect. In the remaining eight sites, the discrepancies could not be
      clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly
      upstaging ten patients to extensive disease and downstaging three patients by not
      confirming metastases of the adrenal glands suspected on the basis of CT. Only
      1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect
      brain metastases. In all cases the stage migration led to a significant change in
      the treatment protocol. Sensitivity of FDG-PET was significantly superior to that
      of CT in the detection of extrathoracic lymph node involvement (100% vs 70%,
      specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%,
      specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than
      cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97%
      vs 100%). CONCLUSION: The introduction of FDG-PET in the diagnostic evaluation of
      SCLC will improve the staging results and affect patient management, and may
      reduce the number of tests and invasive procedures.

PMID- 15258701
TI  - Antibody-based cancer therapies: back to "polyclonals"?

PMID- 15258702
TI  - Congenital (infantile) pseudarthrosis of the fibula associated with osteofibrous
      dysplasia.
AB  - We describe a recently noted association of congenital (infantile) pseudarthrosis
      of the lower leg with osteofibrous dysplasia. The patient was a 2-year-old boy
      who presented with a deformed left ankle joint and three cutaneous cafe-au-lait
      spots. Radiography demonstrated pseudarthrosis of the left distal fibula and a
      round lucent lesion adjacent to the proximal part of the pseudarthrosis.
      Histologically, the surgically removed fibula with pseudarthrosis showed a
      fibromatosis-like fibrovascular proliferation and nonspecific reparative changes.
      The focal lucent area demonstrated a fibro-osseous lesion, which was
      histologically identical to osteofibrous dysplasia. This case provides further
      evidence that osteofibrous dysplasia may be associated with congenital
      (infantile) pseudarthrosis of the lower leg.

PMID- 15258703
TI  - Stress fracture of the medial clavicle secondary to nervous tic.
AB  - The clinical and radiological characteristics of swelling in the region of the
      medial clavicle may suggest the presence of a neoplastic or inflammatory lesion.
      This report describes a 27-year-old man with a painful tumor-like lesion over the
      medial clavicle, which was found to be a stress fracture caused by a nervous tic
      resulting from mental stress.

PMID- 15258704
TI  - MRI of angiomatoid fibrous histiocytoma.
AB  - Angiomatoid fibrous histiocytoma is a rare soft tissue tumor of low-grade
      malignancy. We present the case of a 32-year-old man who complained of soreness
      and numbness over his left arm and hand over the previous 2 months and of having
      a palpable mass over his left upper back for 4 years. Magnetic resonance imaging
      (MRI) showed an intramuscular soft tissue mass in the left scapular region. The
      tumor mass was seen to have multiple cystic components with fluid-fluid levels.
      Histological examination showed multiple cystic spaces filled with blood lakes
      and hemosiderin deposits in the solid part of the tumor. After the initial
      surgery, the patient had local recurrences over 2.5 years. The
      immunohistochemical study at the second surgery showed that the recurrent tumor
      was strongly positive for the histiocytic marker CD68, and the myoid trait
      desmin. Histological diagnosis was compatible with angiomatoid fibrous
      histiocytoma.

PMID- 15258705
TI  - MHC class IIB gene sequences and expression in quails (Coturnix japonica)
      selected for high and low antibody responses.
AB  - Two quail lines, H and L, which were developed for high (H) and low (L) antibody
      production against inactivated Newcastle disease virus antigen, were used to
      examine differences in the organization, structure and expression of the quail
      Mhc class IIB genes. Four Coja class IIB genes in the H line and ten Coja class
      IIB genes in the L line were identified by gene amplification using standard and
      long-range PCRs and sequencing of the amplified products. RFLP analysis,
      sequencing and gene mapping revealed that the H line was fixed for a single class
      IIB haplotype, which we have designated CojaII-02HL- CojaII-01HL. In contrast,
      evidence was found for two class IIB haplotypes segregating in the L line. Some
      individuals were found to be homozygous for haplotype CojaII-08L- CojaII-07L and
      others were found to be heterozygous CojaII-08L- CojaII-07L/ CojaII-02HL- CojaII
      01HL. However, expression of CojaII-02HL- CojaII-01HL was not detected in the L
      line. SRBC immunization induced a measurable antibody response in the serum and a
      line-specific class IIB gene expression in the peripheral white blood cells.
      CojaII-01HL was expressed at the highest level in the H line and CojaII-07L in
      the L line. The expression of the class IIB mRNA reached the highest level at
      approximately 1 week after the primary antibody response and then declined
      exponentially. The antibody and class IIB gene expression data obtained in
      response to SRBC immunization provide further evidence that quails within the L
      line had reduced immunocompetence compared with those in the H line.

PMID- 15258706
TI  - Distribution of HLA class I altered phenotypes in colorectal carcinomas: high
      frequency of HLA haplotype loss associated with loss of heterozygosity in
      chromosome region 6p21.
AB  - HLA class I loss or down-regulation is a widespread mechanism used by tumor cells
      to avoid tumor recognition by cytotoxic T lymphocytes, and thus favor tumor
      immune escape. Multiple mechanisms are responsible for these HLA class I
      alterations. In different epithelial tumors, loss of heterozygosity (LOH) at
      chromosome region 6p21.3, leading to HLA haplotype loss, occurs in 6-50% of all
      cases depending on the tumor entity. In this paper we report the frequency of LOH
      at 6p21 in 95 colorectal carcinomas (CRC) previously analyzed for altered HLA
      class I expression with immunohistological techniques. We used PCR microsatellite
      amplification of selected STR markers located on Chromosome 6 to identify LOH
      with DNA from microdissected tumor tissues and the surrounding stroma. Sequence
      specific oligonucleotide analysis was performed in microdissected stroma and
      tumor cells for HLA typing, and to detect HLA haplotype loss. A high frequency
      (40%) of HLA haplotype loss was found in CRC. Eight tumors showed microsatellite
      instability. We sometimes observed two or more mechanisms responsible for HLA
      alteration within the same HLA-altered phenotype, such as LOH and HLA class I
      total loss. In 25 tumors (26%) no HLA class I alteration could be identified.
      These data are potentially relevant for CRC patients undergoing T-cell-based
      immunotherapy.

PMID- 15258707
TI  - DNA ploidy as a prognostic factor in muscle invasive transitional cell carcinoma
      of the bladder.
AB  - Radical cystectomy represents the treatment of choice for muscle-infiltrative
      bladder carcinoma; however, about 50% of patients relapse and die from the
      disease. In the present study, the prognostic significance of the DNA ploidy in
      transitional cell carcinoma of the urinary bladder (TCCB) is analyzed. The study
      was carried out on 66 patients with TCCB who underwent radical cystectomy. DNA
      ploidy was determined by flow cytometry (FCM) on paraffin-embedded specimens, and
      the results were analyzed and correlated with the tumor malignancy grade and
      stage and the clinical course. Forty of the 66 tumors studied (63%) were
      aneuploid. Aneuploid status was correlated with higher tumor T stage (P < 0.001)
      and grade (P < 0.001). Median follow up was 68 months (range: 12-105). Median
      survival was significantly longer in patients with diploid tumors (> 60 vs 45
      months, P < 0.001). All patients with diploid tumors were alive and free of
      bladder cancer during follow-up, in contrast to only 30% of patients with
      aneuploid tumors. DNA ploidy was an independent prognostic factor, as shown by
      multivariate analysis (P = 0.006). All patients with pT > or = 3b and diploid
      tumors were alive at the time of analysis as opposed to none with aneuploid
      tumors. The results of this study suggest that DNA ploidy can provide prognostic
      information on patients with muscle invasive carcinoma of the bladder and might
      represent a means of selection for postoperative management.

PMID- 15258708
TI  - MR spectroscopy of cervical spinal cord in patients with multiple sclerosis.
AB  - MR spectroscopy (MRS) of the brain in patients with multiple sclerosis has been
      well studied. However, in vivo MRS of the spinal cord in patients with MR
      spectroscopy has not been reported to our knowledge. We performed MRS of normal
      appearing cervical spinal cords in multiple sclerosis patients and in healthy
      controls. N-acetyl aspartate was shown to be reduced within the cervical spinal
      cord of multiple sclerosis patients when compared with healthy controls. This
      finding supports axonal loss and damage within even normal-appearing spinal cords
      of multiple sclerosis patients.

PMID- 15258709
TI  - How does the blood leave the brain? A systematic ultrasound analysis of cerebral
      venous drainage patterns.
AB  - The internal jugular veins are considered to be the main pathways of cerebral
      blood drainage. However, angiographic and anatomical studies show a wide
      anatomical variability and varying degrees of jugular and non-jugular venous
      drainage. The study systematically analyses the types and prevalence of human
      cerebral venous outflow patterns by ultrasound and MRI. Fifty healthy volunteers
      (21 females; 29 males; mean age 27+/-7 years) were studied by color-coded duplex
      sonography. Venous blood volume flow was measured in both internal jugular and
      vertebral veins in the supine position. Furthermore, the global arterial cerebral
      blood volume flow was calculated as the sum of volume flows in both internal
      carotid and vertebral arteries. Three types of venous drainage patterns were
      defined: a total jugular volume flow of more than 2/3 (type 1), between 1/3 and
      2/3 (type 2) and less than 1/3 (type 3) of the global arterial blood flow. 2D TOF
      MR-venography was performed exemplarily in one subject with type-1 and in two
      subjects with type-3 drainage. Type-1 drainage was present in 36 subjects (72%),
      type 2 in 11 subjects (22%) and type 3 in 3 subjects (6%). In the majority of
      subjects in our study population, the internal jugular veins were indeed the main
      drainage vessels in the supine body position. However, a predominantly non
      jugular drainage pattern was found in approximately 6% of subjects.

PMID- 15258710
TI  - Are the configuration and neck morphology of experimental aneurysms predictable?
      A technical approach.
AB  - Aneurysm configuration and neck morphology are important factors in the decision
      for cerebral aneurysm therapy, i.e., clipping versus coiling. The aim of our
      study was to create various aneurysm configurations in a predictable and
      reproducible way in an animal model. In our recently proposed endovascular
      approach to produce bifurcation aneurysms in the rabbit, the right common carotid
      artery (CCA) is surgically exposed and distally ligated, and a sheath is advanced
      retrogradely into the CCA, the base of which is proximally occluded using a
      Fogarty balloon. Subsequently, elastase is injected via a microcatheter that is
      placed directly distal to the balloon and allowed to incubate for 20 min. After
      removal of the sheath, saccular aneurysms begin to form within 2 weeks. For
      greater variability in aneurysm size and neck morphology, we modified two
      parameters of this formerly established elastase-induced aneurysm model--the
      distance between the balloon and sheath and the level of balloon position--before
      the elastase was endoluminally incubated in 15 rabbits. Three weeks after
      aneurysm induction, the size and configuration of the aneurysms were controlled
      using DSA. Our results confirm that balloon occlusion in the brachiocephalic
      trunk results in broad-based aneurysms, whereas balloon occlusion in the CCA
      gives rise to circumscribed aneurysm necks. By increasing the distance between
      the balloon and sheath, the rabbits developed significantly larger aneurysms. The
      balloon-sheath distance and the level of balloon occlusion proved to be
      parameters whose modifications result in predictable and reproducible aneurysm
      variants that can be used for the testing of endovascular devices.

PMID- 15258712
TI  - Probability detection mechanisms and motor learning.
AB  - The automatic detection of patterns or regularities in the environment is central
      to certain forms of motor learning, which are largely procedural and implicit.
      The rules underlying the detection and use of probabilistic information in the
      perceptual-motor domain are largely unknown. We conducted two experiments
      involving a motor learning task with direct and crossed mapping of motor
      responses in which probabilities were present at the stimulus set level, the
      response set level, and at the level of stimulus-response (S-R) mapping. We
      manipulated only one level at a time, while controlling for the other two. The
      results show that probabilities were detected only when present at the S-R
      mapping and motor levels, but not at the perceptual one (experiment 1), unless
      the perceptual features have a dimensional overlap with the S-R mapping rule
      (experiment 2). The effects of probability detection were mostly facilitatory at
      the S-R mapping, both facilitatory and inhibitory at the perceptual level, and
      predominantly inhibitory at the response-set level. The facilitatory effects were
      based on learning the absolute frequencies first and transitional probabilities
      later (for the S-R mapping rule) or both types of information at the same time
      (for perceptual level), whereas the inhibitory effects were based on learning
      first the transitional probabilities. Our data suggest that both absolute
      frequencies and transitional probabilities are used in motor learning, but in
      different temporal orders, according to the probabilistic properties of the
      environment. The results support the idea that separate neural circuits may be
      involved in detecting absolute frequencies as compared to transitional
      probabilities.

PMID- 15258713
TI  - Stretch reflexes in human abdominal muscles.
AB  - Homonymous and heteronymous reflex connections of the abdominal muscles were
      investigated by the application of a tap to the muscle belly and observation of
      surface electromyographic responses. Reflex responses of the following abdominal
      muscles were investigated both ipsilateral and contralateral to the tap: rectus
      abdominis (RA), external oblique (EO) and internal oblique (IO). Reflexes were
      evoked in each of the homonymous muscles with latencies and estimated conduction
      velocities compatible with being evoked by Ia muscle afferents and having a
      monosynaptic component. Short latency heteronymous excitatory reflex connections
      were also observed in muscles on both ipsilateral and contralateral sides in
      response to the same stimulus. The latencies of the crossed responses were only
      marginally longer than responses evoked in the respective ipsilateral muscle.
      Moreover, the reflexes evoked in the IO muscle from ipsilateral and contralateral
      IO muscle afferents were of comparable amplitude, as were those reflexes evoked
      in ipsilateral and contralateral EO and RA muscles when tapping IO. These
      similarities in the reflex characteristics on the ipsilateral and contralateral
      sides suggest that abdominal muscle afferents activate similar pathways to
      muscles on both sides of the body. It follows that if the homonymous stretch
      reflex of abdominal muscles have a monosynaptic component, then a similar
      monosynaptic pathway activates synergistic motoneurones, not only ipsilaterally
      but also contralaterally.

PMID- 15258714
TI  - Proportional myoelectric control of a virtual object to investigate human
      efferent control.
AB  - We used proportional myoelectric control of a one-dimensional virtual object to
      investigate differences in efferent control between the proximal and distal
      muscles of the upper limbs. Eleven subjects placed one of their upper limbs in a
      brace that restricted movement while we recorded electromyography (EMG) signals
      from elbow flexors/extensors or wrist flexors/extensors during isometric
      contractions. By activating their muscles, subjects applied virtual forces to a
      virtual object using a real-time computer interface. The magnitudes of these
      forces were proportional to EMG amplitudes. Subjects used this proportional EMG
      control to move the virtual object through two tracking tasks, one with a static
      target and one with a moving target (i.show $132#e., a sine wave). We
      hypothesized that subjects would have better control over the virtual object
      using their distal muscles rather than using their proximal muscles because
      humans typically use more distal joints to perform fine motor tasks. The results
      indicated that there was no difference in subjects' ability to control virtual
      object movements when using either upper arm muscles or forearm muscles. These
      results suggest that differences in control accuracy between elbow joint
      movements and wrist joint movements are more likely to be a result of motor
      practice, proprioceptive feedback or joint mechanics rather than inherent
      differences in efferent control.

PMID- 15258715
TI  - Planning short pointing sequences.
AB  - An experiment tested the hypothesis that fast, short sequences of movements are
      planned as a whole, before movement inception. The experimental task consisted of
      pointing to either one (one-step condition), or two (two-step condition) visual
      targets aligned along the mid-sagittal axis in a horizontal plane. There were
      nine possible arrangements of the targets resulting from all combinations of
      three distances (5, 10, 15 cm), and two trial orders (blocked or random).
      Performances were characterised by reaction time (RT), movement kinematics, and
      spatial accuracy. Compared with one-step trials, the first movements of two-step
      trials had longer RTs (length effect), particularly in random sessions, and when
      the sequences included short-distance targets. There were also differences in
      duration (one-target advantage), velocity profile and spatial accuracy that did
      not depend on the characteristics of the second movement. The results are
      inconsistent with the assumption that two-step sequences are planned as a whole.
      Instead, they are in keeping with the alternative hypothesis that part of the
      preparation of the second step takes place during the execution of the first
      step.

PMID- 15258716
TI  - Assessing methylphenidate preference in ADHD patients using a choice procedure.
AB  - RATIONALE: Methylphenidate (MPH) is widely used in the treatment of attention
      deficit hyperactivity disorder (ADHD) and is associated with positive clinical
      effects across a wide range of domains. Despite the clinical effectiveness of
      MPH, concern has arisen with respect to its abuse potential. OBJECTIVES: To
      assess MPH preference in adults diagnosed with ADHD using a choice procedure and
      to evaluate the relationship among drug preference, therapeutic efficacy, and
      abuse potential in a clinical sample. METHODS: Participants were ten volunteers
      (ages 18-22 years) with ADHD who were receiving MPH treatment. Preference was
      assessed using a double-blind choice procedure with four sampling sessions
      wherein subjects received either placebo or MPH and eight choice sessions when
      they chose either capsule or no capsules. RESULTS: Overall, MPH was chosen
      significantly more often than placebo (chi2=52.5; P<0.001) and participants were
      equally separated into groups of those who chose MPH reliably (MPH choosers) and
      those who did not (MPH non-choosers). MPH decreased ADHD symptoms and resulted in
      lower ratings of stimulant effects among MPH choosers. MPH choosers also reported
      higher levels of baseline ADHD symptoms. CONCLUSIONS: Despite higher preference
      of MPH than placebo in this clinical sample, other measures of abuse potential
      were not elevated, and MPH choosers were more symptomatic than non-choosers. As
      such, MPH preference in ADHD populations likely reflects therapeutic efficacy
      rather than abuse potential. Future work should examine MPH choice in diagnosed
      and non-diagnosed populations to further explore the role of clinical efficacy in
      the preference of this stimulant drug.

PMID- 15258717
TI  - The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique
      clinical effects of clozapine.
AB  - RATIONALE: Clozapine is a unique antipsychotic, with efficacy against positive
      symptoms in treatment-resistant schizophrenic patients, and the ability to
      improve cognition and treat the negative symptoms characteristic of this disease.
      Despite its unique clinical actions, no specific molecular mechanism responsible
      for these actions has yet been described. OBJECTIVES AND METHODS: To
      comprehensively profile a large library of neuropsychiatric drugs, including most
      antipsychotics, at human monoamine receptors using R-SAT, an in vitro functional
      assay. RESULTS: Profiling revealed that N-desmethylclozapine (NDMC), the
      principal metabolite of clozapine, but not clozapine itself, is a potent and
      efficacious muscarinic receptor agonist, a molecular property not shared by any
      other antipsychotic. To further explore the role of NDMC muscarinic receptor
      agonist properties in mediating the physiological actions of clozapine,
      systemically administered NDMC was found to stimulate the phosphorylation of
      mitogen-activated protein kinase (MAP kinase) in mouse CA1 hippocampal neurons,
      an effect that was blocked by scopolamine, confirming central M1 muscarinic
      receptor agonist activity in vivo. Lastly, an analysis of clozapine and NDMC
      serum levels in schizophrenic patients indicated that high NDMC/clozapine ratios
      better predicted improvement in cognitive functioning and quality of life than
      the levels of either compound alone. CONCLUSIONS: The muscarinic receptor agonist
      activities of NDMC are unique among antipsychotics, and provide a possible
      molecular basis for the superior clinical effects of clozapine pharmacotherapy.

PMID- 15258719
TI  - Neonatal isolation enhances maintenance but not reinstatement of cocaine self
      administration in adult male rats.
AB  - RATIONALE: Previously, we demonstrated that neonatal isolation increases
      acquisition of cocaine self-administration in adult male rats. OBJECTIVE: Now we
      examine whether neonatal isolation enhances maintenance and cocaine-induced
      reinstatement of extinguished self-administration behavior. To test the
      specificity of the effect, a separate study examined maintenance of food
      responding. METHODS: Litters were subjected to neonatal isolation (individual
      isolation; 1 h/day; postnatal days 2-9) or were non-handled. In experiment 1,
      adult male rats trained to self-administer cocaine (0.5 mg/kg per infusion; fixed
      ratio 3 or FR3) were tested under fixed and progressive ratio (PR) schedules with
      different cocaine doses (0.125-1.0 mg/kg per infusion). After cocaine self
      administration was extinguished, cocaine (0.5 or 2 mg/kg)-induced reinstatement
      of responding was assessed. In experiment 2, responding for food under an FR15
      and two PR schedules were assessed in separate groups of neonatally isolated and
      non-handled male rats. RESULTS: Neonatally isolated rats responded for low
      cocaine doses at higher rates and infused more cocaine relative to non-handled
      rats under both FR and PR schedules. However, there are no group differences in
      cocaine-induced reinstatement or in responding for food under the PR schedules.
      However, neonatally isolated rats lever pressed for food at lower rates under the
      FR schedule. CONCLUSIONS: Together with our previous studies, the results of the
      present study suggest that the early life stress of neonatal isolation enhances
      cocaine-taking (acquisition and maintenance) at lower doses but does not alter
      drug-induced cocaine-seeking (reinstatement) behavior.

PMID- 15258718
TI  - Efficacy of low and higher dose extended-release venlafaxine in generalized
      social anxiety disorder: a 6-month randomized controlled trial.
AB  - RATIONALE: There is a need for new pharmacological treatments for generalized
      social anxiety disorder (GSAD), which is a common, often disabling condition.
      OBJECTIVE: To compare the efficacy and safety over 6 months duration of two dose
      ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD.
      METHOD: Twenty-eight-week, double-blind, multi-center study in 386 adult
      outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER
      fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150-225
      mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety
      Scale (LSAS). Secondary efficacy variables included, among others, the proportion
      of responders on the CGI Global Improvement Item (score 1 or 2), and the
      proportion of remitters (defined as an LSAS score of <or=30). RESULTS:
      Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150-225
      mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients
      receiving venlafaxine ER (at any dose), 58% responded to treatment compared to
      33% of those receiving placebo (P<0.001); corresponding remission rates were 31%
      and 16% (P<0.01). There were no differences in outcome according to venlafaxine
      ER dosage. CONCLUSIONS: Venlafaxine ER was effective in the treatment of GSAD.
      The comparable efficacy at low and higher doses may indicate that norepinephrine
      reuptake blockade does not contribute to therapeutic effect in GSAD. This
      hypothesis should be tested using agents with specific actions on norepinephrine
      reuptake blockade.

PMID- 15258720
TI  - Distribution and sub-cellular localization of the aflatoxin enzyme versicolorin B
      synthase in time-fractionated colonies of Aspergillus parasiticus.
AB  - Aflatoxins are highly toxic and carcinogenic fungal secondary metabolites. At
      least 18 enzyme activities are required for aflatoxin biosynthesis in the
      filamentous fungus Aspergillus parasiticus. One of these enzymes, versicolorin B
      synthase (VBS), catalyzes bisfuran ring closure in versiconal hemiacetal (a
      reaction near the middle of the pathway) to form versicolorin B. This reaction is
      required for the subsequent activation to aflatoxin B1-8,9 epoxide, a highly
      reactive and toxic aflatoxin metabolite, and is important for aflatoxin toxicity.
      We analyzed the localization of VBS in the aflatoxin-producing strain A.
      parasiticus SU-1 grown on solid media using a colony fractionation technique
      developed previously. A highly specific polyclonal antibody, raised against a
      maltose-binding protein-VBS fusion protein synthesized in Escherichia coli, was
      used to detect VBS in SU-1 grown on a rich solid medium via immunofluorescence
      confocal laser scanning microscopy (CLSM) and immunogold transmission electron
      microscopy (TEM). VBS was detected in both vegetative hyphae and in asexual
      developmental structures, called conidiophores. Western blot and CLSM analyses
      demonstrated the highest abundance of VBS in colony fraction S2 consisting of
      cells that had grown for 24-48 h; this fraction also contained the highest levels
      of newly developed conidiophores and the highest abundance of aflatoxin B1,
      consistent with VBS abundance. At the subcellular level, CLSM and TEM detected
      VBS distributed throughout the cytoplasm and concentrated in ring-like structures
      surrounding nuclei. It is uncertain whether enzymatically active VBS is present
      in either or both locations.

PMID- 15258721
TI  - Do vegetarians have a normal bone mass?
AB  - Public health strategies targeting the prevention of poor bone health on a
      population-wide basis are urgently required, with particular emphasis being
      placed on modifiable factors such as nutrition. The aim of this review was to
      assess the impact of a vegetarian diet on indices of skeletal integrity to
      address specifically whether vegetarians have a normal bone mass. Analysis of
      existing literature, through a combination of observational, clinical and
      intervention studies were assessed in relation to bone health for the following:
      lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets,
      consumption of animal versus vegetable protein, and fruit and vegetable
      consumption. Mechanisms of action for a dietary "component" effect were examined
      and other potential dietary differences between vegetarians and non-vegetarians
      were also explored. Key findings included: (i) no differences in bone health
      indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for
      protein effects on bone with high protein consumption (particularly without
      supporting calcium/alkali intakes) and low protein intake (particularly with
      respect to vegan diets) being detrimental to the skeleton; (iii) growing support
      for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of
      action currently remaining unclarified. The impact of a "vegetarian" diet on bone
      health is a hugely complex area since: 1) components of the diet (such as
      calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key
      lifestyle factors which are important to bone (such as physical activity) may be
      different; 3) the tools available for assessing consumption of food are
      relatively weak. However, from data available and given the limitations
      stipulated above, "vegetarians" do certainly appear to have "normal" bone mass.
      What remains our challenge is to determine what components of a vegetarian diet
      are of particular benefit to bone, at what levels and under which mechanisms.

PMID- 15258722
TI  - Reduced bone mineral density in male renal transplant recipients: evidence for
      persisting hyperparathyroidism.
AB  - BACKGROUND: Osteoporosis is increasingly recognized as a major source of
      morbidity following renal transplantation. The aim of this cross-sectional study
      was to determine the prevalence of osteoporosis in a cohort of male transplant
      recipients and examine factors that may influence their bone loss. METHODS: Bone
      mineral density (BMD) and biochemical markers of bone metabolism were measured in
      134 out of 154 male renal allograft recipients in our center. RESULTS: The mean
      age of the patients was 49.7 years (range 26-76) with a median of 6 years post
      transplant. Only 17% had normal BMD, 30% were osteoporotic at either hip or
      spine, and this proportion rose to 41% if the ultradistal radius was included.
      Parathyroid hormone (PTH) was negatively correlated with BMD at all skeletal
      sites. In a multiple regression model, independent predictors of femoral neck BMD
      included body mass index (p=0.004), diabetes (p=0.025), and PTH (p=0.049). The
      only independent predictor of BMD at the ultradistal radius was PTH (p<0.001).
      Nineteen men sustained a total of 25 appendicular fractures after transplantation
      (median time to fracture was 3 years). Prevalent vertebral fractures were only
      identified in five men. PTH was elevated in 72.4% of patients (mean PTH 142 +/-
      118 pg/ml). Bone resorption markers were increased in 48% of patients. PTH was
      positively correlated with serum carboxyterminal telopeptide of type 1 collagen
      (r=0.473, p<0.001) and procollagen type 1 amino terminal propeptide (r=0.419,
      p<0.001). CONCLUSIONS: Osteopenia and osteoporosis are common in male transplant
      recipients, and the hip and radius are the most severely affected sites. Elevated
      rates of bone resorption driven by hyperparathyroidism appear to be the most
      important contributing factor.

PMID- 15258723
TI  - Estrogen receptor alpha gene analysis in osteoporosis and familial osteoporosis.
AB  - Estrogens are important determinants of bone mineral density (BMD) mediating
      their effects via estrogen receptor alpha (ERalpha) and beta (ERbeta). The strong
      genetic predisposition to osteoporosis, and the fact that alterations in the
      aminoterminal region of ERalpha have been linked to bone disturbances, prompted
      us to identify genetic alterations in exon 1 and exon 2 of ERalpha in
      osteoporotic individuals. Sixty-two unrelated normal subjects (age 46.1+/-9.5
      years) and 72 unrelated osteoporotic subjects (age 52.3+/-7.9 years) were
      studied. Their menopausal status was pre- and perimenopausal. We also included 30
      related osteoporotic individuals (mother-daughter or sister-sister relationship)
      (age 46.2+/-12.8 years) belonging to 14 families who where also pre- and
      perimenopausal. DNA was extracted from peripheral blood, exons 1 and 2 were
      amplified by polymerase chain reaction (PCR) and were further submitted to
      denaturing gradient gel electrophoresis (DGGE), single stranded conformational
      polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and sequence
      analysis. Bone turnover markers were also determined. Two polymorphisms were
      identified in exon 1 (codons 10 and 87) in both normal and osteoporotic women.
      Statistical analysis revealed no difference (P>0.05) in the ERalpha genotype
      frequencies within osteoporotic families as compared with the same genotypes in
      the unrelated normal or osteoporotic subjects. Codon 10, codon 87 polymorphisms
      were not related to BMD or bone turnover markers. No other mutations were found
      in exons 1 and 2 in all subjects studied. Genetic alterations in exons 1 and 2 of
      ERalpha are not associated to osteoporosis and familial osteoporosis. Moreover,
      the codon 10 and codon 87 polymorphisms do not seem to be correlated with BMD and
      bone turnover markers.

PMID- 15258724
TI  - Practice patterns in the diagnosis and treatment of osteoporosis after a
      fragility fracture: a systematic review.
AB  - Fragility fractures are a strong indicator of underlying osteoporosis (OP). With
      the risk of future fracture being increased 1.5- to 9.5-fold following a
      fragility fracture, the diagnosis and treatment of OP in men and women with
      fragility fractures provides the opportunity to prevent future fragility
      fractures. This review describes the current status of practice in investigation
      and diagnosis of OP in men and women with fragility fractures, the rates and
      types of postfracture treatment in patients with fragility fractures and OP,
      interventions undertaken in this population, and the barriers to OP
      identification and treatment. A literature search performed in Medline,
      Healthstar, CINAHL, EMBASE, PreMedline, the Cochrane Central Register of
      Controlled Trials, and the Cochrane Database of Systematic Reviews identified 37
      studies on OP diagnosis, treatment, and interventions. The studies varied in
      design methodology, study facilities, types of fractures, and pharmacological
      treatments. Some studies revealed that no patients with fragility fractures
      received investigation or treatment for underlying OP. Investigation of OP by
      bone mineral density was low: 14 of 16 studies reported investigation of less
      than 32% of patients. Investigation by bone mineral density resulted in high
      rates of OP diagnosis (35-100%), but only moderate use of calcium and vitamin D
      (8-62%, median 18%) and bisphosphates (0.5-38%) in patients investigated
      postfracture. Studies on barriers to OP identification and treatment focused on
      various groups of health practitioners. Barriers included the cost of therapies,
      time and cost of resources for diagnosis, concerns about medications, and the
      lack of clarity regarding the responsibility to undertake this care.

PMID- 15258726
TI  - Transfusion-transmitted malaria.

PMID- 15258727
TI  - Co-morbidity and acute decompensations of COPD requiring non-invasive positive
      pressure ventilation.
AB  - OBJECTIVE: To assess the prevalence and the impact of chronic and/or acute non
      respiratory co-morbidity on short and longer-term outcome of non-invasive
      positive pressure ventilation (NIPPV) in acute decompensations of chronic
      obstructive pulmonary disease (COPD) with acute hypercapnic respiratory failure
      (AHRF). DESIGN AND SETTING: An observational study in a three-bed respiratory
      monitoring unit in a respiratory ward of a non-university hospital. PATIENTS: We
      grouped 120 consecutive COPD patients requiring NIPPV for AHRF (pH 7.28+/-0.05,
      PaO2/FIO2 ratio 192+/-63, PaCO2 78.3+/-12.3 mmHg) according to whether NIPPV
      succeeded (n=98) or failed (n=22) in avoiding the need for endotracheal
      intubation and whether alive (n=77) or dead (n=42) at 6 months. MEASUREMENTS AND
      RESULTS: The prevalence of chronic and acute co-morbidity was, respectively, 20%
      and 41.7%; most of the cases were cardiovascular. In-hospital NIPPV failure was
      greater in patients with than in those without chronic (33.3% vs. 14.6%) or acute
      co-morbidity (32% vs. 8.6%). Six-month mortality was worse in patients with than
      in those without chronic (54.2% vs. 30.5%) or more than one acute co-morbidity
      (66.7% vs. 30.8%). Multiple regression analysis predicted in-hospital NIPPV
      failure by acute co-morbidity and forced expiratory volume in 1 s, while death at
      6 months was predicted by having more than one acute co-morbidity, non
      cardiovascular chronic co-morbidity and Activities of Daily Living score.
      CONCLUSIONS: Chronic and acute co-morbidities are common in COPD patients with
      AHRF needing NIPPV and their presence influences short and longer-term outcome.

PMID- 15258728
TI  - Pulmonary endothelium in acute lung injury: from basic science to the critically
      ill.
AB  - BACKGROUND: Pulmonary endothelium is an active organ possessing numerous
      physiological, immunological, and metabolic functions. These functions may be
      altered early in acute lung injury (ALI) and further contribute to the
      development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium
      is strategically located to filter the entire blood before it enters the systemic
      circulation; consequently its integrity is essential for the maintenance of
      adequate homeostasis in both the pulmonary and systemic circulations. Noxious
      agents that affect pulmonary endothelium induce alterations in hemodynamics and
      hemofluidity, promote interactions with circulating blood cells, and lead to
      increased vascular permeability and pulmonary edema formation. OBJECTIVE: We
      highlight pathogenic mechanisms of pulmonary endothelial injury and their
      clinical implications in ALI/ARDS patients.

PMID- 15258729
TI  - Emotional strain, communication, and satisfaction of family members in the
      intensive care unit compared with expectations of the medical staff: experiences
      from a Norwegian University Hospital.
AB  - OBJECTIVES: To determine satisfaction in regard to information concerning, and
      support and facilities for relatives in the intensive care unit (ICU), and to
      compare this with the staff's expectations on these issues; to determine
      relatives' degree of psychological distress and use of hypnotics, anxiolytics,
      and antidepressants; finally, to compare the distress of relatives of survivors
      and relatives of non-survivors. DESIGN: Prospective study. SETTING: University
      affiliated ICU. METHODS: Relatives of 50 patients who survived at least 6 days in
      the ICU and relatives of 18 non-survivors who stayed for at least 24 h
      anonymously completed a mailed questionnaire at home 4 weeks after treatment in
      the ICU. Forty-three staff members (69%) answered the questionnaire. The degree
      of satisfaction was measured on a five-point scale (0-4). MAIN RESULTS: The
      average satisfaction scores were 3.4+/-0.6 SD for relatives of survivors and
      3.4+/-0.5 for relatives of non-survivors. Staff expected a significantly lower
      degree of satisfaction, with a score of 2.9+/-0.5 (P<0.001). The distress scores
      of relatives of survivors (2.7+/-1.0) were no higher than the ones of relatives
      of non-survivors (2.4+/-0.6) during the ICU stay, but significantly lower than
      staff expectations (3.2+/-0.5) (P<0.01). The use of medication was moderate.
      CONCLUSIONS: The relatives' satisfaction was greater than anticipated by the
      staff. Staff generally expected a higher degree of distress among relatives than
      was actually the case. Relatives were very satisfied with the support and
      communication in the ICU despite substantial distress. Relatives of survivors and
      non-survivors were equally satisfied.

PMID- 15258730
TI  - Hydrostatic mechanisms may contribute to the pathogenesis of human re-expansion
      pulmonary edema.
AB  - OBJECTIVE: The primary objective was to test the hypothesis that clinical re
      expansion pulmonary edema is predominantly due to increased permeability of the
      alveolar-capillary barrier. A secondary objective was to determine if the
      alveolar epithelium was functionally intact in patients with re-expansion
      pulmonary edema by measuring net alveolar epithelial fluid transport in a subset
      of patients. DESIGN: Retrospective study of mechanically ventilated patients with
      re-expansion pulmonary edema. SETTING: Two academic tertiary care hospitals.
      PATIENTS: Seven patients with acute onset of re-expansion pulmonary edema after
      tube thoracostomy or thoracentesis. INTERVENTIONS: Pulmonary edema fluid and
      plasma were collected at the time of onset of re-expansion edema. MEASUREMENTS
      AND RESULTS: Contrary to our hypothesis, the mean initial edema fluid to plasma
      protein ratio was 0.58+/-0.21, supporting a hydrostatic mechanism of edema
      formation. Four of the patients had an initial edema fluid to plasma protein
      ratio of less than 0.65, consistent with pure hydrostatic pulmonary edema, while
      the others had a slight increase in permeability (edema fluid to plasma ratios of
      0.67, 0.71 and 0.77), perhaps due to capillary stress failure from hydrostatic
      stress. Alveolar fluid clearance (mean 9.8+/-8.0%/h) was intact in the subset of
      three patients in whom it was measured. CONCLUSIONS: This study provides the
      first direct evidence that hydrostatic forces may contribute to the development
      of re-expansion pulmonary edema.

PMID- 15258731
TI  - Oxygen transport-the oxygen delivery controversy.

PMID- 15258732
TI  - Fluids reverse the early lipopolysaccharide-induced albumin leakage in rodent
      mesenteric venules.
AB  - OBJECTIVE: Volume resuscitation is clinically beneficial in patients with sepsis,
      but few data exist concerning the effects of fluid administration on early events
      in the inflammatory process. Vascular permeability, leukocyte rolling and
      leukocyte adhesion in the rodent mesenteric microcirculation were assessed in
      vivo using intravital microscopy, and the effect of fluid administration on
      lipopolysaccharide (LPS)-induced changes recorded. DESIGN: Prospective, repeated
      measures study. SETTING: University hospital laboratory. SUBJECTS: Male Wistar
      rats in six groups. INTERVENTIONS: All animals underwent intravital microscopic
      examination of mesenteric post-capillary venules. LPS or vehicle was applied
      topically. Animals received either no additional fluids, 0.9% saline (16 ml/kg
      per h) or 5% human albumin (16 ml/kg per h) commencing 30 min prior to
      LPS/vehicle administration. MEASUREMENTS AND MAIN RESULTS: Leukocyte rolling,
      firm adhesion and blood velocity were observed directly. Vascular permeability
      was assessed using the flux of fluorescently labelled albumin into the
      interstitium. LPS significantly increased the median (IQR) number of leukocytes
      rolling and firmly adherent relative to baseline (at 60 min rolling increased
      from 12.0 (10.3-13.8) to 40.3 (36.0-47.5) cells/min; adhesion increased from 1 (1
      2) to 17 (12-26) cells/100 microm; n=5, p<0.01). Transvascular albumin flux was
      significantly increased 45 min after LPS application (p<0.01), but not after
      vehicle. Administration of either 0.9% saline (n=5) or 5% human albumin (n=6),
      significantly attenuated LPS-induced increases in albumin flux (p<0.05),
      leukocyte rolling (p<0.01) and adhesion (p<0.01). Fluid administration did not
      appear to alter shear rates. CONCLUSIONS: Pre-emptive volume administration with
      either saline or albumin prevented early LPS-induced microcirculatory changes by
      an undefined effect that is unrelated to changes in microvascular flow.

PMID- 15258733
TI  - [The value of instrumented gait analysis in infantile cerebral palsy].
AB  - The technique of instrumented gait analysis enables the physician to exactly
      document spastic gait disorders. Time-distance parameters, joint kinematics and
      kinetics, dynamic EMG recordings and the measurement of energy consumption
      provide an extensive insight into gait problems. This method is used not only for
      diagnostic purposes but also to monitor the effects of therapeutic interventions.
      A significant limitation is the specialist knowledge necessary to interpret the
      data. For an adequate assessment, the gait data must be supplemented by clinical
      and radiological findings. When interpreting gait analysis reports, technical
      errors must always be born in mind. The subjectivity of individual interpretation
      is the major reason for the considerable variability in the treatment
      recommendations for similar patients.

PMID- 15258734
TI  - [Surgical treatment of secondary hip dislocation in cerebral palsy].
AB  - The surgical treatment of secondary dislocation of the hip is one of the most
      challenging issues in cerebral palsy. The selection and application of adequate
      surgical techniques require an outstanding knowledge of pathophysiology in order
      to achieve a good outcome with minimal operative expenditure. The hips of
      cerebral palsied children show no pathological findings at birth. The dislocation
      of the hip is a secondary process, due to the influence of permanently
      deteriorating muscle dysbalances that first cause a decentration and finally
      result in a complete dislocation. Physiotherapeutic treatment supports the
      development of gait, muscle balance and weight bearing in the early childhood,
      however, severe hip dislocation can not be prevented with physiotherapy alone.
      Surgical treatment aims to prevent hip dislocation in order to maintain the
      ability to walk and to sit, and to avoid secondary skin ulcers. Soft tissue
      release is performed to neutralize muscle dysbalances. Progressive dislocation
      requires extended surgical treatment. The combination of soft tissue release,
      varisation osteotomy and acetabular osteotomy enable an adequate repositioning of
      the hip and have proved to preserve hips from reluxation. Palliative operations
      including soft tissue release in combination with angulation osteotomy, and
      proximal femoral head resection are restricted to failed reconstruction
      operations or severe luxations, and are performed to attempt pain reduction or
      the facilitation of perineal care. Surgical planning distinguishes patients able
      to walk from those who are unable to walk or to sit without support. The
      manifestation of cerebral palsy and the aim of adequate pain reduction and the
      maintenance of statomotoric abilities also have a great impact on surgical
      planning. The treatment of secondary hip dislocation in cerebral palsy is
      facilitated by the use of a graduated treatment concept with early preventive
      soft tissue release, extended reconstruction and optional palliative care.

PMID- 15258735
TI  - Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation
      end product, are associated with proliferative diabetic retinopathy and macular
      oedema.
AB  - AIMS/HYPOTHESIS: Diabetic retinopathy is a frequent microvascular complication.
      In search of novel risk markers, we analysed the association between serum levels
      of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML)
      and prevalence of advanced stages of retinopathy in Type 2 diabetic patients
      without nephropathy. METHODS: We carried out a case-control study of Type 2
      diabetic patients with and without advanced stages of diabetic retinopathy.
      Retinopathy and macular oedema were defined according to standard criteria. Serum
      levels of CML were estimated by means of a novel competition-based ELISA assay.
      RESULTS: Serum levels of CML were significantly different between age-matched
      controls (n=792; mean value +/- SD: 521+/-134 ng/ml), Type 2 diabetic patients
      without severe retinopathy (821+/-141 ng/ml; p<0.0001) and Type 2 diabetic
      patients with proliferative retinopathy (1182+/-346 ng/ml; p<0.0001). Levels of
      CML greater than 1000 ng/ml represented a 25-fold increase in risk of
      proliferative retinopathy. Receiver operating characteristics analysis revealed a
      CML threshold of 1087 ng/ml (100% sensitivity, 93% specificity) for clinically
      significant macular oedema. CONCLUSIONS/INTERPRETATION: High serum levels of CML
      were associated with advanced stages of retinopathy. Serum levels were shown to
      be a progressive risk marker, whereby a level of more than 1000 ng/ml induced a
      25-fold increase in risk of proliferative retinopathy and clinically significant
      macular oedema. Our data suggest that serum levels of CML provide a novel risk
      marker for advanced stages of diabetic retinopathy in Type 2 diabetic patients.

PMID- 15258736
TI  - Long-term evaluation of a structured outpatient education programme for
      intensified insulin therapy in patients with Type 1 diabetes: a 12-year follow
      up.
AB  - AIMS/HYPOTHESIS: This study was conducted to evaluate the long-term outcome of a
      structured outpatient diabetes teaching and treatment programme (DTTP) for
      intensified insulin therapy in patients with Type 1 diabetes, which aims to
      improve metabolic control without increasing the risk of severe hypoglycaemia.
      METHODS: All 123 diabetic outpatients (age 41+/-14 years; 64 women; BMI 23.5+/
      3.1; diabetes duration 17+/-11 years; HbA1c 7.9+/-1.6%; 32 patients with a
      history of severe hypoglycaemia; 18 with overt nephropathy; 22 with proliferative
      retinopathy) who participated in the DTTP between June 1989 and June 1990 were
      invited for follow-up visits after 3, 6 and 12 years. RESULTS: Out of the 123
      patients, 11 died during the follow-up period, two were lost for follow-up, and
      one was not willing to participate in re-evaluation after 12 years. Mean HbA1c
      levels decreased from 7.9+/-1.6% to 7.1+/-1.2% (p<0.01) after 3 years, and were
      7.8+/-1.5% (NS) and 7.8+/-1.2% (NS) after 6 and 12 years respectively. Frequency
      of hypoglycaemia decreased from 0.49 episodes per patient per year to 0.14 after
      3 years (p<0.01), 0.19 after 6 years (p<0.01) and 0.16 after 12 years (p<0.01).
      Of the participants, 41% were able to lower HbA1c levels without episodes of
      severe hypoglycaemia and to maintain this improvement at all follow-up visits
      over the 12-year period. At follow-up, intensified insulin therapy was carried
      out by 94% of the patients. CONCLUSIONS/INTERPRETATION: A sustained reduction of
      the incidence of severe hypoglycaemia was observed in patients with Type 1
      diabetes after participation in a structured outpatient DTTP over a 12-year
      period.

PMID- 15258737
TI  - Large-scale studies of the functional K variant of the butyrylcholinesterase gene
      in relation to Type 2 diabetes and insulin secretion.
AB  - AIMS/HYPOTHESIS: Polymorphisms of the butyrylcholinesterase gene (BCHE) are
      reported to associate with Alzheimer's disease and a recent study found a
      significant association of the BCHE K variant (G1615A/Ala539Thr) with Type 2
      diabetes. The objectives of our study were to examine whether the BCHE K variant
      is associated with Type 2 diabetes or estimates of pancreatic beta cell function
      in large-scale populations of glucose-tolerant Caucasians. METHODS: The variant
      was genotyped in association studies comprising a total of 1408 Type 2 diabetic
      patients and 4935 glucose-tolerant control subjects. Genotype-phenotype studies
      were carried out in the 4935 glucose-tolerant control subjects. RESULTS: There
      was no difference in allele frequency between Type 2 diabetic patients and
      control subjects (20.3% [95% confidence interval: 18.8-21.8] vs 20.4% [19.6
      21.2], non-significant). In the genotype-phenotype studies we found no consistent
      association with BMI, fasting or post-OGTT plasma glucose, serum insulin or serum
      C-peptide levels. CONCLUSIONS/INTERPRETATION: The present study does not support
      the suggestion that the BCHE K polymorphism is associated with Type 2 diabetes or
      with estimates of pancreatic beta cell function in large-scale Danish Caucasian
      populations.

PMID- 15258738
TI  - Type 2 diabetes mellitus--genes or intrauterine environment? An embryo transfer
      paradigm in rats.
AB  - AIMS/HYPOTHESIS: The familial predisposition to Type 2 diabetes mellitus is
      mediated by both genetic and intrauterine environmental factors. In the normal
      course of events, maternal genes always develop in the same uterus, thus
      restricting studies aimed at investigating the relative contribution of these
      factors. We have developed an embryo transfer paradigm in rats to overcome this
      difficulty. METHODS: Euglycaemic female Wistar rats were superovulated and mated
      with male Wistar rats. The following day, fertilised eggs were transferred into
      pseudo-pregnant female Wistar rats or hyperglycaemic Goto Kakizaki (GK) rats.
      Pregnancies were allowed to go to term. Offspring were weighed at 6 weeks, 3
      months and 6 months of age and an intravenous glucose tolerance test was carried
      out at 6 months of age. RESULTS: Offspring from Wistar into Wistar embryo
      transfers (n=20) were not significantly hyperglycaemic compared to the non
      manipulated Wistar stock colony (n=26). However, offspring from Wistar gametes
      reared in hyperglycaemic GK mothers (n=51) were significantly lighter at 6 weeks
      of age (156+/-4.1 g vs 180+/-6.1 g [mean +/- SEM], p<0.01) and significantly more
      hyperglycaemic at 6 months of age (fasting glucose 6.6+/-0.18 mmol/l vs 4.8+/
      0.21 mmol/l, mean blood glucose during glucose tolerance test 14.3+/-0.31 mmol/l
      vs 11.1+/-0.28 mmol/l, p<0.01) than Wistar gametes transferred back into
      euglycaemic Wistar mothers. When GK rats were superovulated and mated together,
      transfer of 1-day-old embryos into pseudo-pregnant Wistar dams did not alleviate
      hyperglycaemia in adult offspring. CONCLUSIONS/INTERPRETATION: In GK rats, a
      euglycaemic intrauterine environment cannot overcome the strong genetic
      predisposition to diabetes. However, in Wistar rats with a low genetic risk of
      diabetes, exposure to hyperglycaemia in utero significantly increases the risk of
      diabetes in adult life.

PMID- 15258739
TI  - Isolation and mapping of resistance gene analogs from the Avena strigosa genome.
AB  - Degenerate primers based on conserved regions of the nucleotide binding site
      (NBS) domain (encoded by the largest group of cloned plant disease resistance
      genes) were used to isolate a set of 15 resistance gene analogs (RGA) from the
      diploid species Avena strigosa Schreb. These were grouped into seven classes on
      the basis of 60% or greater nucleic acid sequence identity. Representative clones
      were used for genetic mapping in diploid and hexaploid oats. Two RGAs were mapped
      at two loci of the linkage group AswBF belonging to the A. strigosa x A. wiestii
      Steud map, and ten RGAs were mapped at 15 loci in eight linkage groups belonging
      to the A. byzantina C. Koch cv. Kanota x A. sativa L. cv. Ogle map. A similar
      approach was used for targeting genes encoding receptor-like kinases. Three
      different sequences were obtained and mapped to two linkage groups of the
      hexaploid oat map. Associations were explored between already known disease
      resistance loci mapped in different populations and the RGAs. Molecular markers
      previously linked to crown rust and barley yellow dwarf resistance genes or
      quantitative trait loci were found in the Kanota x Ogle map linked to RGAs at a
      distance ranging from 0 cM to 20 cM. Homoeologous RGAs were found to be linked to
      loci either conferring resistance to different isolates of the same pathogen or
      to different pathogens. This suggests that these RGAs identify genome regions
      containing resistance gene clusters.

PMID- 15258740
TI  - Identification and genetic characterization of an Aegilops tauschii ortholog of
      the wheat leaf rust disease resistance gene Lr1.
AB  - Aegilops tauschii (goat grass) is the progenitor of the D genome in hexaploid
      bread wheat. We have screened more than 200 Ae. tauschii accessions for
      resistance against leaf rust (Puccinia triticina) isolates,which are avirulent on
      the leaf rust resistance gene Lrl. Approximately 3.5% of the Ae. tauschii
      accessions displayed the same low infection type as the tester line Thatcher Lrl.
      The accession Tr.t. 213, which showed resistance after artificial infection with
      Lrl isolates both in Mexico and in Switzerland, was chosen for further analysis.
      Genetic analysis showed that the resistance in this accession is controlled by a
      single dominant gene,which mapped at the same chromosomal position as Lrl in
      wheat. It was delimited in a 1.3-cM region between the restriction fragment
      length polymorphism (RFLP) markers ABC718 and PSR567 on chromosome 5DL of
      Ae.tauschii. The gene was more tightly linked to PSR567(0.47 cM) than to ABC718
      (0.79 cM). These results indicate that the resistance gene in Ae. tauschii
      accession Tr.t. 213 is an ortholog of the leaf rust resistance gene Lrlof bread
      wheat, suggesting that Lrl originally evolved in diploid goat grass and was
      introgressed into the wheat D genome during or after domestication of
      hexaploidwheat. Compared to hexaploid wheat, higher marker polymorphism and
      recombination frequencies were ob-served in the region of the Lrl ortholog in Ae.
      tauschii. The identification of LrlAe, the orthologous gene of wheatLrl, in Ae.
      tauschii will allow map-based cloning of Lrlfrom this genetically simpler,
      diploid genome.

PMID- 15258742
TI  - [Voice-improving laser-surgical therapy in amyloidosis of the larynx].
AB  - Laryngeal amyloidosis is relatively uncommon, accounting for only 0.2-1.5% of all
      laryngeal tumours. Hoarseness, dysphagia and stridor are potential clinical
      symptoms. A systemic amyloidosis should be excluded even though symptoms are only
      apparent in the head and neck region. For the localised form, surgical excision
      of the excess tissue is performed. We discuss the development of the disease,
      together with its diagnostics and therapy, based on the case report of a 42 year
      old female patient.

PMID- 15258743
TI  - [Completion pneumonectomy. Indications and results].
AB  - Completion pneumonectomy (CP) is widely known to be associated with high
      morbidity and lethality. However, in certain instances, it offers the only chance
      for cure. The results of the following CPs (N=86) were investigated: progressive
      or recurrent benign disease (N=6, group I), recurrence of a malignant tumor
      (N=41, group II), and complication after lung resection (N=39, group III). Right
      completion pneumonectomy was carried out in 48 cases and left completion
      pneumonectomy in 38. The overall 30-day lethality of CP was 20.2%, 0% in group I,
      10% n group II, and 33.3% n group III. This lethality was significantly higher on
      the right side (29.8%) than on the left (7.7%; P=0.014). Differentiation between
      emergency and urgent indications resulted in 30-day lethalities of 54% and 23%,
      respectively. This difference is significant (P=0.002). The 30-day lethality for
      patients with anastomotic or stump insufficiency was 41% (P=0.002). Five-year
      survival was 26% in the group of patients with malignant disease and 32% in those
      with complications after lung resection. The results show: the lethality of CP
      remains high, especially after complications from operating in emergency
      conditions. However, considering the long-term survival, CP is certainly
      justified.

PMID- 15258744
TI  - [Long-term cosmetic results following thyroid resection].
AB  - BACKGROUND: The long-term cosmetic results following thyroid resection may soon
      become more relevant because minimally invasive techniques are also being
      promoted. PATIENTS AND METHODS: Two hundred forty-four patients were
      prospectively enrolled for a questionnaire regarding long-term results following
      thyroid resection. Ninety of these patients were clinically examined. RESULTS:
      The cosmetic results were judged by more than 90% of the patients as excellent or
      good. Women were slightly more critical about their results (P=0.06). Some kind
      of wound infection was reported in 4.1%, hypertrophic scar in 4.1%, and mild
      dysphagia in 7%. The results were not associated with the kind or extent of
      resection. The length of the scars was 4 cm (range 3-7) and the width 2 mm (range
      1-4). The surgeons also judged the scars as good or excellent in most cases but
      were more critical than the patients. CONCLUSION: Since the long-term results of
      conventional surgery are, in most cases, so good, it seems difficult to improve
      the results by new minimally invasive techniques.

PMID- 15258745
TI  - [What is evidence based in the therapy of pelvic floor insufficiency?].

PMID- 15258746
TI  - [Obstructed defecation].
AB  - Adequate therapy of obstructed defecation (pelvic outlet obstruction) is often
      challenging, as the etiology and clinical symptoms include a wide range of
      disorders. Standardized diagnostic assessment has to differentiate between
      obstructed defecation caused by either pelvic outlet obstruction or slow transit
      constipation. Additionally, morphologic changes of colon, rectum, or the pelvic
      floor have to be separated from functional disorders. Providing defecography or
      dynamic MR of the pelvic floor, common causes of outlet obstruction such as
      sigmoidoceles, in which surgery is indicated, and rectal prolapse can be
      diagnosed with high accuracy. However, the diagnosis and therapeutic options in
      symptomatic rectocele and intussusception are controversial. Patients with
      functional disorders such as rectoanal dyssynergia are candidates for
      conservative treatment (biofeedback). To identify patients who will benefit from
      surgery for obstructed defecation, careful patient selection remains the crucial
      issue in diagnostic assessment.

PMID- 15258747
TI  - [Differential diagnosis in descending perineum syndrome].
AB  - Clinical symptoms in descending perineum syndrome show considerable variations,
      ranging from obstructed defecation to combined fecal and urinary incontinence and
      including different types of prolapse. Differential diagnosis has to compete with
      this complexity. Common pelvic floor disorders associated with descending
      perineum are rectocele, rectal prolapse, enterocele, and sigmoidocele.
      Standardized diagnostic tools include detailed history and clinical examination
      with proctorectoscopy as well as anorectal manometry, endoanal ultrasound,
      defecography, and dynamic MR of the pelvic floor. The diagnosis and proposed
      therapy have to be developed within an interdisciplinary concept.

PMID- 15258748
TI  - [Fecal incontinence].
AB  - Diagnosis and management of fecal incontinence requires exact understanding of
      the anatomic and pathophysiologic principles involved and demands a methodical,
      stepwise approach. Despite the potential appeal of surgical intervention, a
      considerable number of patients can be helped by comparatively simple,
      noninvasive measures. Initial treatment should be medical, including biofeedback
      in combination with a bowel management program. In the presence of a severely
      denervated pelvic floor, physiotherapeutic techniques rarely give rise to a
      satisfactory and long-lasting response. Obvious external sphincter defects and
      patients who failed medical management are treated surgically. Many injuries of
      the external sphincter can be treated by direct sphincter repair. If patients
      with intact external sphincters are unresponsive to medical measures, descending
      perineum and resultant idiopathic fecal incontinence will improve by radio
      frequency delivery, sacral nerve stimulation, or postanal plication. Patients
      with complex neurologic disorders or extensive sphincter defects or who have
      undergone previous unsuccessful attempts at repair of the puborectalis itself
      should be considered for dynamic gracilis plastic or an artificial sphincter.

PMID- 15258749
TI  - [Controversies in the treatment of carotid stenoses. Present state of research
      and evidence-based medicine].
AB  - Endarterectomy for extracranial carotid stenosis has proven to be effective in
      the prophylaxis of carotid-related strokes by prospective, randomised trials
      (ECST, NASCET, ACAS, ACST). The safety and efficiency of carotid stenting has to
      be proven in prospective randomised trials comparing surgery and endovascular
      treatment.

PMID- 15258750
TI  - [Organ transplantation in human immunodeficiency virus-infected patients. Results
      of a survey in German transplantation centres].
AB  - BACKGROUND: Despite considerable advances following the introduction of highly
      active antiretroviral therapy, organ transplantation is usually denied
      categorically for human immunodeficiency virus (HIV) patients, and it is
      presented in German transplantation law as a contraindication. Today, this should
      be questioned critically. METHOD: A survey at all 87 German transplant centres
      was done concerning (1) how many HIV-positive patients were transplanted before
      and after February 2000, (2) willingness of the centres to transplant HIV
      infected patients in the future, and (3) course of transplanted HIV patients so
      far. RESULTS: With a response rate of 78%, 39% of the questioned centres were
      accepting HIV patients in the future for transplantation, and 39% rejected this.
      Twenty percent voted for individual case decision. Three centres had practiced
      liver transplantation in 11 patients. CONCLUSION: The decision to transplant HIV
      positive patients in Germany is mostly based on individual cases and not refused
      in general. However, prospective studies on this issue are justified and needed.

PMID- 15258751
TI  - [Expandable cages: biomechanical comparison of different cages for ventral
      spondylodesis in the thoracolumbar spine].
AB  - INTRODUCTION: Due to a recent increase in the commercial availability of
      expandable cages for vertebral body replacement, this study was designed to gain
      more information about their biomechanical properties. All three expandable cages
      evaluated in this study are approved for clinical use, but little knowledge about
      their biomechanical properties exists. MATERIAL AND METHODS: Human thoracolumbar
      spines (T11 to L3) ( n=32) were tested in flexion, extension, axial rotation, and
      lateral bending with a nondestructive stiffness method. Three-dimensional
      displacement was measured using an optical measurement system. All motion
      segments were tested intact. After L1 corporectomy, cages were implanted and the
      following groups ( n=8 each) were tested: (1) meshed titanium cage (nonexpandable
      cage, DePuy Acromed), (2) X-tenz (expandable cage, DePuy Acromed), (3) Synex
      (expandable Cage, Synthes), and (4) VBR (expandable cage, Ulrich). Finally,
      posterior stabilization and posterior-anterior stabilization, both using USS
      (Synthes), and anterior plating (LCDCP, Synthes) was applied. The mean apparent
      stiffness values, ranges of motion, and neutral and elastic zones were calculated
      from the corresponding load/displacement curves. RESULTS: No significant
      differences were found between the in vitro biomechanical properties of
      expandable and nonexpandable cages. Compared to the intact motion segment,
      isolated anterior stabilization using cages and anterior plating significantly
      decreased stiffness and increased range of motion in all directions. Additional
      posterior stabilization significantly increased stiffness and decreased range of
      motion in all directions compared to the intact motion segment. Combined anterior
      posterior stabilization demonstrated the greatest stiffness results. CONCLUSION:
      Design variations of expandable cages for vertebral body replacement do not show
      any significant effect on the biomechanical results. There was no significant
      difference found, between the biomechanical properties of expandable and non
      expandable cages. After corporectomy, isolated implantation of expandable cages
      plus anterior plating was not able to restore normal stability of the motion
      segment. As a consequence, isolated anterior stabilization using cages plus LCDCP
      should not be used for vertebral body replacement in the thoraco-lumbar spine.

PMID- 15258752
TI  - [Differential diagnosis of saccular aneurysms of the isthmus aortae: example of a
      penetrating atherosclerotic ulcer. Case-report and review of the literature].
AB  - Most aneurysms of the isthmus aortae, particularly those following thoracic
      trauma, are most likely to be diagnosed as acute dissecting or post-traumatic
      pseudoaneurysms. Furthermore, penetrating atherosclerotic ulcers in patients with
      atherosclerosis, congenital aneurysms such as ductus diverticulum and Kommerell's
      diverticulum, luetic aneurysms, and saccular aneurysms associated with Marfan's
      syndrome have to be included in the list of differential diagnoses. In view of
      the severe effect of any open thoracic surgical intervention, exact preoperative
      diagnosis is crucial. We report the case of a 73-year-old male patient who was
      accidentally diagnosed with an aneurysm of the atherosclerotic isthmus aortae.
      The aneurysm extended from the aorta to the dorsal site. The sacciform aneurysm
      (4.5 cm) was resected electively. Based upon localisation and pathomorphological
      findings, a penetrating ulcer was diagnosed. We also present a review of the
      current literature and give a survey of the differential diagnoses of aneurysms
      of the aortic isthmus: penetrating atherosclerotic ulcus, acute (traumatic)
      dissecting aneurysm, post-traumatic pseudoaneurysm, ductus diverticulum,
      Kommerell's diverticulum, syphilitic aneurysm, and sacciform aneurysm due to
      Marfan's syndrome.

PMID- 15258753
TI  - Gefitinib ('IRESSA', ZD1839) inhibits EGF-induced invasion in prostate cancer
      cells by suppressing PI3 K/AKT activation.
AB  - PURPOSE: Androgen-independent prostate cancer (AI-PC) is characterized by a
      higher invasive potential compared to hormone-responsive prostate cancer. A
      therapeutic option for AI-PC should thus be targeted to suppress not only cell
      proliferation, but also the invasive ability of the cells. Here, we investigated
      the effect of the epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor gefitinib ('IRESSA', ZD1839) on EGF-stimulated invasion and
      proliferation in two androgen-independent prostate cancer cell lines PC3 and
      DU145. In addition, we determined the effect of the compound on EGF-stimulated
      PI3 K/AKT pathway activation, in view of the key role exerted by this pathway in
      carcinoma cell invasion. METHODS: Cell proliferation was determined by thymidine
      incorporation in the nuclei. Cell cycle analysis was performed by flow cytometry.
      Invasion through matrigel in vitro was measured by using Boyden chambers. PI3 K
      activity was measured by immunokinase assay and AKT phosphorylation was evaluated
      by Western blot analysis. RESULTS: Gefitinib inhibits invasion through matrigel
      and collagen in response to EGF in both cell lines. In addition, we confirm the
      inhibitory effect of the compound on basal and EGF-induced cell proliferation.
      Such an effect was accompanied by accumulation of the cells in the G0/G1 phase of
      the cell cycle. The effect of the compound is due, as expected, to suppression of
      EGF-induced autotransphosphorylation of EGFR. In addition, we demonstrate here
      that gefitinib inhibits EGF-induced activation of PI3 K/AKT pathway in both cell
      lines. CONCLUSION: Overall, our results demonstrate that gefitinib is able to
      suppress invasion and proliferation of AI-PC cells by suppressing EGF-stimulated
      activation of the PI3 K/AKT pathway and support a possible use of the drug in the
      treatment of advanced PC to limit not only proliferation but also invasion to
      other districts.

PMID- 15258754
TI  - Quality of adjuvant CMF chemotherapy for node-positive primary breast cancer: a
      population-based study.
AB  - PURPOSE: Adjuvant 'classical' oral cyclophosphamide, methotrexate, and 5
      fluorouracil (CMF) has long been the mainstay of adjuvant chemotherapy for
      premenopausal breast cancer patients. The Comprehensive Cancer Center North
      Netherlands (CCCN) breast cancer working group performed a retrospective audit of
      treatment guideline adherence and quality of CMF in hospitals in the CCCN area.
      METHODS: The CMF treatment data of 251 consecutive axillary lymph node-positive
      breast cancer patients <50 years old, diagnosed between 1993 and 1996, were
      analyzed. RESULTS: Ninety-four patients (42%) completed adjuvant CMF without dose
      adjustment or delay. Overall median relative dose intensity (RDI) was 92.6 (IQR
      85.5-97.7). Sixty patients (24%) had an RDI <85, and 7% had an RDI <65.
      Myelotoxicity was the main reason for reductions and delays. Of 176 irradiated
      patients, 96% received radiotherapy simultaneously with CMF. Median CMF dose
      intensity nor median duration differed between patients who underwent mastectomy,
      mastectomy and radiotherapy, or breast-conserving therapy. Radiotherapy did not
      influence the median RDI (94 without versus 92 with radiotherapy). G-CSF,
      administered at least once to 76 patients, did not result in a higher median RDI.
      Median RDI was slightly higher when >3 patients/year (P=0.014) were treated by
      one specialist or >10 patients classified for adjuvant chemotherapy yearly in a
      hospital (P=0.037). CONCLUSION: The adherence to CMF treatment guidelines was
      generally good. Simultaneous radiotherapy did not affect the median RDI of CMF. G
      CSF had no impact on the median RDI but patient volume did influence the RDI.

PMID- 15258755
TI  - A comprehensive in vitro characterization of pancreatic ductal carcinoma cell
      line biological behavior and its correlation with the structural and genetic
      profile.
AB  - There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL)
      that are used by researchers worldwide. Detailed data about their differentiation
      status and genetic alterations are present in the literature, but a systematic
      correlation with cell biological behavior is often lacking. PDCL ( n=12) were
      clustered by source of tumor cell (ascites, primary tumor, metastasis), and the
      data of functional cell biology were correlated with the reported structural and
      genetic profiles. Major histocompatibility complex expression, chemosensitivity
      and aneuploidia appeared to be related to the source of PDCL, and proliferative
      capacity appeared to be related to the grade of differentiation. No correlation
      between genetic/structural features of PDCL and biological behavior was found.
      All the cell lines appeared generally insensitive to in vitro treatment with 5
      fluorouracil and showed variable degrees of susceptibility to gemcitabine,
      raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated
      apoptosis but were significantly sensitive to the pro-apoptotic effect of
      inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha
      and interferon gamma]. PDCL were characterized for the secretion of several
      factors relevant to the tumor-immune cross talk. Vascular endothelial growth
      factor, CCL2, CCL5 and transforming growth factor beta were the factors most
      frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and
      sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1beta
      and TNFalpha were always undetectable. In conclusion, a clear correlation between
      structural/genetic features and function could not be detected, suggesting the
      weakness of a "morphological" classification for the in vitro studies of
      pancreatic cancer.

PMID- 15258756
TI  - Array comparative genomic hybridisation analysis of gamma-irradiated human
      thyrocytes.
AB  - The susceptibility of thyroid epithelium to radiation-induced carcinogenesis is
      well recognised. In this context, thyroid carcinogenesis is associated with
      specific somatic ret/papillary thyroid carcinoma (PTC) rearrangements and
      morphologically with the papillary phenotype. Previous studies have demonstrated
      the possibility of inducing ret rearrangements in vitro using X-rays. The purpose
      of our study was to assess whether gamma (gamma) radiation using a Caesium 137
      source can induce specific ret rearrangements in a human thyroid epithelial cell
      culture model. We further hypothesised that if radiation-induced thyroid
      carcinogenesis is associated with non-random rearrangement events, then DNA copy
      gain and loss induced by irradiation may also occur in a non-random manner. We
      irradiated SV40-immortalised human thyroid epithelial cells with incremental
      doses of gamma-radiation and, using TaqMan reverse-transcription polymerase chain
      reaction, looked for the presence of the common ret rearrangements. Cohorts
      showing evidence of ret/PTC chimeric transcripts were further analysed using
      microarray comparative genomic hybridisation (CGH) to detect copy gain and loss
      associated with radiation. Four Grays of gamma-radiation was sufficient to induce
      ret/PTC-3. In this model, transcripts of ret/PTC-1 were not detected, and we
      suggest that the type of radiation may influence the resulting rearrangement that
      occurs. Using array CGH, we have demonstrated a predominant pattern of
      subtelomeric deletions occurring in association with this radiation cohort and
      raise the possibility that chromosome 10 may be a hotspot for radiation-induced
      damage for as yet unknown reasons.

PMID- 15258757
TI  - Lymphoepithelioma-like carcinoma of the submandibular salivary gland associated
      with Epstein-Barr virus in a North African woman.

PMID- 15258759
TI  - Potential mechanisms of low-temperature tolerance of C4 photosynthesis in
      Miscanthus x giganteus: an in vivo analysis.
AB  - Miscanthus x giganteus (Greef & Deuter ex Hodkinson & Renvoize) is unique among
      C4 species in its remarkable ability to maintain high photosynthetic productivity
      at low temperature, by contrast to the related C4 NADP-malic enzyme-type species
      Zea mays L. In order to determine the in vivo physiological basis of this
      difference in photosynthesis, water vapor and CO2 exchange and modulated
      chlorophyll fluorescence were simultaneously monitored on attached leaf segments
      from plants grown and measured at 25/20 degrees C or 14/11 degrees C (day/night
      temperature). Analysis of the response of photosynthesis to internal CO2
      concentration suggested that ribulose bisphosphate carboxylase/oxygenase
      (Rubisco) and/or pyruvate orthophosphate dikinase (PPDK) play a more important
      role in determining the response to low temperature than does phosphoenolpyruvate
      carboxylase (PEPc). For both species at both temperatures, the linear
      relationship between operating efficiency of whole-chain electron transport
      through photosystem II (Phi(PSII)) and the efficiency of CO2 assimilation
      (Phi(CO2)) was unchanged and had a zero intercept, suggesting the absence of non
      photosynthetic electron sinks. The major limitation at low temperature could not
      be solely at Rubisco or at any other point in the Calvin cycle, since this would
      have increased leakage of CO2 to the mesophyll and increased Phi(PSII)/Phi(CO2).
      This in vivo analysis suggested that maintenance of high photosynthetic rates in
      M. x giganteus at low temperature, in contrast to Z. mays, is most likely the
      result of different properties of Rubisco and/or PPDK, reduced susceptibility to
      photoinhibition, and the ability to maintain high levels of leaf absorptance
      during growth at low temperature.

PMID- 15258760
TI  - Proteomic analysis of molecular response to oxidative stress by the green alga
      Haematococcus pluvialis (Chlorophyceae).
AB  - Rapidly growing, green motile flagellates of Haematococcus pluvialis can
      transform into enlarged red resting cysts (aplanospores) under oxidative stress
      conditions. However, it is not known what initial molecular defense mechanisms
      occur in response to oxidative stress, and may ultimately lead to cellular
      transformation. In this study, global-expression profiling of cellular proteins
      in response to stress was analyzed by two-dimensional gel electrophoresis, image
      analysis, and peptide mass fingerprinting. Oxidative stress was induced in
      cultures of green flagellates by addition of acetate and Fe2+, and exposure to
      excess light intensity. Overall, 70 proteins were identified with altered
      expression patterns following stress induction. Some key proteins involved in
      photosynthesis and nitrogen assimilation were down-regulated, whereas some
      mitochondrial respiratory proteins were transiently up-regulated after the onset
      of stress. Most of the identified proteins, particularly those from the families
      of superoxide dismutase, catalase, and peroxidase, were transiently up-regulated,
      but reverted to down-regulation during the 6 days of stress. On the other hand,
      cellular accumulation of the antioxidant astaxanthin occurred well after
      initiation of oxidative stress and reached its maximum cellular level after six
      or more days of stress. It appears that the early stress response involves
      multiple enzymatic defense processes that play a critical role upon onset of
      stress and also during the early transition of green vegetative cells to red
      cysts. As cyst development continues, the intensive, enzyme-mediated initial
      responses were largely replaced in mature red cysts by accumulation of the
      molecular antioxidant astaxanthin. This study provides the first direct evidence
      for a massive, and concerted up-regulation of multiple antioxidative defense
      mechanisms, both spatially and temporarily, to protect H. pluvialis cells against
      oxidative stress.

PMID- 15258761
TI  - Localization of two homologous Arabidopsis kinesin-related proteins in the
      phragmoplast.
AB  - During plant cytokinesis, kinesin-related motor proteins are believed to play
      critical roles in microtubule organization and vesicle transport in the
      phragmoplast. Previously, we reported that the motor AtPAKRP1 was associated with
      the plus end of phragmoplast microtubules in Arabidopsis thaliana [Lee Y-RJ, Liu
      B (2000) Curr Biol 10:797-800]. In this paper, we report a full-length cDNA from
      the same organism, which encodes a polypeptide 74% identical to AtPAKRP1. This
      AtPAKRP1-like protein--AtPAKRP1L--and AtPAKRP1 share similar domain structures
      along the polypeptides. Peptide antibodies were raised and purified to
      distinguish the two polypeptides in vitro and in vivo. When monospecific anti
      AtPAKRP1 and anti-AtPAKRP1L antibodies were used in immunofluorescence, they both
      decorated the plus end of phragmoplast microtubules at all stages of phragmoplast
      development. Their localization patterns were indistinguishable from each other.
      By using bacterially expressed fusion proteins of motor-less versions of both
      polypeptides, it was revealed that AtPAKRP1 and AtPAKRP1L were able to interact
      with themselves and with each other. Using T-DNA insertional mutants, it was also
      demonstrated that AtPAKRP1 and AtPAKRP1L were not required for each other's
      localization. Our results therefore indicate that AtPAKRP1 and AtPAKRP1L are both
      expressed in the same cells, and likely have identical functions in the
      phragmoplast by forming either homodimers or heterodimers.

PMID- 15258762
TI  - Intracellular localization of VDAC proteins in plants.
AB  - Voltage-dependent anion channels (VDACs) are porin-type beta-barrel diffusion
      pores. They are prominent in the outer membrane of mitochondria and facilitate
      metabolite exchange between the organelle and the cytosol. Here we studied the
      subcellular distribution of a plant VDAC-like protein between plastids and
      mitochondria in green and non-green tissue. Using in vitro studies of dual-import
      into mitochondria and chloroplasts as well as transient expression of
      fluorescence-labeled polypeptides, it could be clearly demonstrated that this
      VDAC isoform targets exclusively to mitochondria and not to plastids. Our results
      support the idea that plastids evolved a concept of solute exchange with the
      cytosol different from that of mitochondria.

PMID- 15258763
TI  - Electrophysiological and proarrhythmic parameters in transmural canine left
      ventricular needle biopsies.
AB  - This study was designed to validate the use of small, transmural, left
      ventricular biopsies in the dog for investigations of electrophysiological and
      proarrhythmic properties of the heart. This technique could facilitate
      pharmacological in vitro testing in remodelled hearts of both man and animal.
      Small, transmural, semi-cylindrical, left-ventricular biopsies from dogs with
      normal sinus rhythm (SR) were characterized electrophysiologically and compared
      with biopsies from electrically remodelled hearts from dogs with chronic,
      complete AV-block (CAVB). In at least five biopsy segments recordings were made
      to determine the action potential duration (APD), the transmural gradient of
      repolarization, the maximal transmural dispersion (deltatM(max)) and presence of
      early after-depolarizations (EADs) at different pacing cycle lengths (PCLs) in
      the absence and presence of a class-III agent, ibutilide (10(-6) M). The biopsies
      showed stable and normal AP characteristics, a conduction velocity of 0.22 +/-
      0.05 m/s and normal frequency dependence of the APD. The location of the longest
      APD varied, thus creating transmural repolarization gradients with differing
      morphology. Ibutilide prolonged the APD, accentuated repolarization gradients and
      induced EADs. CAVB biopsies had significantly longer APDs, a larger dispersion of
      repolarization and showed more EADs in the presence of ibutilide than SR
      biopsies. We conclude that this biopsy technique provides coherent and valid
      transmural electrophysiological data in dogs under various conditions.

PMID- 15258764
TI  - Oestradiol rapidly inhibits Ca2+ signals in ciliary neurons through classical
      oestrogen receptors in cytoplasm.
AB  - Oestrogen plays a key role in a great variety of actions in the nervous system,
      either through classical or alternative pathways. The classical pathways are
      initiated after oestrogen binding to the oestrogen receptors ERalpha or ERbeta,
      which translocate from the cytoplasm to the nucleus and act there as
      transcription factors. Alternative pathways are initiated at the plasma membrane
      and cytoplasm, via binding to classical or non-classical ERs. Using isolated
      ciliary ganglion neurons from the chick embryo and Ca2+ imaging, we demonstrated
      that a 10-min exposure to 17beta-oestradiol reduces Ca2+ influx through the
      plasma membrane. This effect was not reproduced by oestradiol conjugated to
      bovine serum albumin, which does not cross the plasma membrane, indicating that
      17beta-oestradiol was acting intracellularly. ERalpha was detected in the
      cytoplasm by immunostaining and its involvement in the regulation of Ca2+ influx
      by ICI182,780 inhibition. The phosphatidylinositol-3 kinase (Pi3-kinase)
      inhibitor wortmannin and the nitric oxide synthase (NOS) inhibitor Nomega-nitro-L
      arginine methyl ester (L-NAME) both blocked the oestradiol effect. The oestradiol
      effect was reproduced by 8Br-cGMP and abolished in the presence of the cGMP
      dependent protein kinase (PKG) inhibitor KT5823. Our study indicates that 17beta
      oestradiol can regulate Ca2+ influx via PI3-kinase, NOS and PKG after activation
      of cytoplasmic ER.

PMID- 15258765
TI  - Chloride transport in the renal proximal tubule.
AB  - The renal proximal tubule is responsible for most of the renal sodium, chloride,
      and bicarbonate reabsorption. Micropuncture studies and electrophysiological
      techniques have furnished the bulk of our knowledge about the physiology of this
      tubular segment. As a consequence of the leakiness of this epithelium,
      paracellular ionic transport--in particular that of Cl(-)--is of considerable
      importance in this first part of the nephron. It was long accepted that proximal
      Cl(-) reabsorption proceeds solely paracellularly, but it is now known that
      transcellular Cl(-) transport also exists. Cl(-) channels and Cl(-)-coupled
      transporters are involved in transcellular Cl(-) transport. In the apical
      membrane, Cl(-)/anion (formate, oxalate and bicarbonate) exchangers represent the
      first step in transcellular Cl(-) reabsorption. A basolateral Cl(-)/HCO(3)(-)
      exchanger, involved in HCO(3)(-) reclamation, participates in the rise of
      intracellular Cl(-) activity above its equilibrium value, and thus also
      contributes to the creation of an outwardly directed electrochemical Cl(-)
      gradient across the cell membranes. This driving force favours Cl(-) diffusion
      from the cell to the lumen and to the interstitium. In the basolateral membrane,
      the main mechanism for transcellular Cl(-) reabsorption is a Cl(-) conductance,
      but a Na(+)-driven Cl(-)/HCO(3)(-) exchanger may also participate in Cl(-)
      reabsorption.

PMID- 15258766
TI  - Extracellular Mg(2+) blocks endothelin-1-induced contraction through the
      inhibition of non-selective cation channels in coronary smooth muscle.
AB  - This study investigated the effects of changing the extracellular [Mg(2+)]
      ([Mg(2+)](o)) on endothelin-1 (ET-1)-induced contraction of rabbit coronary
      artery smooth muscle and the involvement of non-selective cation (NSC) channels
      in this response. Increased [Mg(2+)](o) shifted the concentration/contraction
      relationship curve of ET-1 to the right. In whole-cell patch clamp recordings, ET
      1 (10(-7) M) induced a long-lasting inwards current (94.7+/-7.2 pA) that was
      inhibited by 8 mM [Mg(2+)](o) (45.3+/-4.4%) and NSC channel blockers (10(-3) M
      streptomycin and 10(-3) M La(3+)), but not by the voltage-dependent Ca(2+)
      channel blocker nicardipine. The current/voltage (I/V) curve was linear.
      Furthermore, in pressurized arteries, the ET-1-induced contraction was also
      inhibited by La(3+) and streptomycin, but not by nicardipine. U-73122, a
      selective phospholipase C (PLC) inhibitor and staurosporine and GF 109203X, which
      block protein kinase C (PKC), reduced ET-1-activated NSC currents by 54.2+/-5.1%,
      60.3+/-5.5% and 48.5+/-2.9%, respectively. The inwards current was increased by 1
      oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12,13-dibutyrate (PDBu), which
      activate PKC selectively. Like transient receptor potential channel (TRPC3)
      currents, ET-1-activated NSC currents had a linear I/V relationship, were blocked
      by flufenamate and activated by a diacylglycerol analogue. These results suggest
      that [Mg(2+)](o) blocks ET-1-induced contraction of coronary arteries by
      inhibiting NSC channels. Activation of PLC and PKC might be involved in
      activation of NSC channels.

PMID- 15258767
TI  - Lack of association of delta-aminolevulinic acid dehydratase genotype with
      cytogenetic damage in lead workers.
AB  - OBJECTIVE: The objective of this study was to evaluate the correlations of
      genetic polymorphism of genotypes delta-aminolevulinic acid dehydratase (ALAD),
      blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges
      (SCEs), and high SCE frequency cells (HFCs) in lead workers. METHODS: Three
      groups of lead workers were included in the study: high lead exposure group (26
      workers), low lead exposure group (31 workers) and control group (30 controls who
      lived in an area uncontaminated by lead). Blood samples were taken from all
      subjects and analyzed for lead levels, ALAD genotype and SCE levels. RESULTS:
      Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin
      levels than the controls. There were no differences among the three groups
      regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2
      genotype was not detected in any of the three groups. There were no significant
      differences among the three groups for BLLs, ZPP and hemoglobin levels based on
      ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were
      significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P <
      0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the
      high lead exposure group than in the low lead exposure group (16.1%) and the
      control group (10%). There appeared to be an interaction effect on HFC
      percentages between smoking and lead exposure. When multiple regression analysis
      was used, the factors that affected SCE levels were lead exposure and smoking,
      but ALAD genotypes did not have any significant effect. CONCLUSIONS: A
      significant association existed between both SCE and HFC levels and lead
      exposure. However, different ALAD genotypes were not found to be associated with
      levels of blood lead and ZPP in the three groups.

PMID- 15258768
TI  - Development of nerves expressing P2X3 receptors in the myenteric plexus of rat
      stomach.
AB  - Development of neurones and fibres expressing P2X3 receptors in the myenteric
      plexus of rat stomach and coexistence of the P2X3 receptor with calbindin,
      calretinin and NOS during postnatal development, were investigated with
      immunostaining methods. Extrinsic nerves expressing P2X3 receptors appeared as
      early as E12 and were localised in the trunk and branches of the vagus nerve,
      which extended rapidly onto the whole rat stomach from E12 to E14. Intrinsic
      neurone cell bodies with P2X3-immunoreactivity in the myenteric ganglia were
      first demonstrated postnatally at P1, and at P14, when the number of neurones
      expressing the P2X3 receptor peaked at 45%. P2X3 receptor-immunoreactivity
      decreased subsequently, and at P60 only about 11% were P2X3-immunoreactive.
      Intraganglionic laminar nerve endings and intramuscular arrays were first
      demonstrated postnatally at P1 and P7, respectively. In the early postnatal days,
      there were many growth cone-like structures with strong P2X3 immunostaining
      associated with these endings and arrays. Double-immunostaining showed that 9-15%
      of P2X3-immunoreactive neurones in the gastric myenteric plexus expressed
      calbindin D-28 k only in the early postnatal days, while 14-21% of neurones from
      P1 to P60 increasingly expressed calretinin. About 20% of neurones with P2X3
      immunoreactivity coexpressed NOS throughout perinatal development.

PMID- 15258769
TI  - Dynamic imaging of cellular interactions with extracellular matrix.
AB  - Adhesive and proteolytic interactions of cells with components of the
      extracellular matrix (ECM) are fundamental to morphogenesis, tissue assembly and
      remodeling, and cell migration as well as signal acquisition from tissue-bound
      factors. The visualization from fixed samples provides snapshot-like, static
      information on the cellular and molecular dynamics of adhesion receptor and
      protease functions toward ECM, such as interstitial fibrillar tissues and
      basement membranes. Recent technological developments additionally support the
      dynamic imaging of ECM scaffolds and the interaction behavior of cells contained
      therein. These include differential interference contrast, confocal reflection
      microscopy, optical coherence tomography, and multiphoton microscopy and second
      harmonic generation imaging. Most of these approaches are combined with
      fluorescence imaging using derivates of GFP and/or other fluorescent dyes.
      Dynamic 3D imaging has revealed an unexpected degree of dynamics and turnover of
      cell adhesion and migration as well as basic mechanisms that lead to proteolytic
      remodeling of connective tissue by stromal cells and invading tumor cells.

PMID- 15258770
TI  - Alteration of podocytes in a murine model of crescentic glomerulonephritis.
AB  - Recent observations suggest a central role of podocytes in crescent formation. In
      experimental glomerulonephritis podocytes disrupt the parietal epithelial layer
      and attach on its basement membrane, thus forming bridges between the tuft and
      Bowman's capsule, and they are a major constituent of crescents. In order to
      explain these findings we hypothesize that inflammation triggers motility in
      podocytes. In the present study we asked whether podocytes display alterations
      which suggest a migratory behavior in glomerulonephritis. Glomerulonephritis was
      induced in mice by injection of a rabbit serum against the glomerular basement
      membrane. The kidneys were perfusion-fixed 6 days later and examined by light and
      electron microscopy as well as by immunohistochemistry. In glomerulonephritis the
      apical cytoplasm of podocytes displayed numerous actin-containing
      microprotrusions. Cortactin, a protein involved in the regulation of actin
      polymerization, was predominantly expressed in foot processes of podocytes in
      control mice. It was redistributed to the cell body in glomerulonephritis. In
      untreated mice betal-integrin was restricted to the foot processes. In
      glomerulonephritis it was additionally found in the cytoplasm and in the apical
      cell membrane. Recycling of integrins is a crucial event in initiation of cell
      migration. ICAM-1 and CD44, the ligation of which induces migratory behaviors,
      were absent from healthy podocytes but expressed by some podocytes in
      glomerulonephritis. Thus, in glomerulonephritis podocytes display some
      characteristic features of migrating cells. This might explain their ability to
      break through the parietal epithelium and to become a constituent of early
      crescents.

PMID- 15258771
TI  - Blood-brain barrier disruption in the hypothalamus of young adult spontaneously
      hypertensive rats.
AB  - Vascular permeability and endothelial glycocalyx were examined in young adult
      spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), and Wistar Kyoto
      rats (WKY) as a control, in order to determine earlier changes in the blood-brain
      barrier (BBB) in the hypothalamus in chronic hypertension. These rats were
      injected with horseradish peroxidase (HRP) as an indicator of vascular
      permeability. Brain slices were developed with a chromogen and further examined
      with cationized ferritin, a marker for evaluating glycocalyx. Staining for HRP
      was seen around vessels in the hypothalamus of SHR and SHRSP, but was scarce in
      WKY. The reaction product of HRP appeared in the abluminal pits of endothelial
      cells and within the basal lamina of arterioles, showing increased vascular
      permeability in the hypothalamus of SHR and SHRSP, whereas there were no leaky
      vessels in the frontal cortex of SHR and SHRSP, or in both areas of WKY. The
      number of cationized ferritin particles binding to the capillary endothelial
      cells was decreased in the hypothalamus of SHR and SHRSP, while the number
      decreased in the frontal cortex of SHRSP, compared with those in WKY. Cationized
      ferritin binding was preserved in some leaky arterioles, while it was scarce or
      disappeared in other leaky vessels. These findings suggest that BBB disruption
      occurs in the hypothalamus of 3-month-old SHR and SHRSP, and that endothelial
      glycocalyx is markedly damaged there without a close relationship to the early
      changes in the BBB.

PMID- 15258772
TI  - Applications of an efficient method for comparing immunogold labelling patterns
      in the same sets of compartments in different groups of cells.
AB  - Quantitative immunoelectron microscopy often involves determining the
      distributions of gold label in different intracellular compartments and then
      drawing comparisons between compartments in the same sample of cells or between
      experimental groups of cells. In the case of within-group comparisons, recent
      developments in the estimation of relative labelling index and labelling density
      make it possible to test whether or not particular compartments are
      preferentially labelled. These methods are ideally suited to analysing gold label
      restricted to volume (organelle) or surface (membrane) compartments but may be
      modified to analyse label localised in mixtures of both. Here, a simple and
      efficient approach to drawing between-group comparisons for label associated with
      organelles and/or membranes is presented. The method relies on multistage random
      sampling of specimens (via blocks and microscopic fields) followed by simply
      counting gold particles associated with different compartments. The distributions
      of raw gold counts in different groups are then compared by contingency table
      analysis with statistical degrees of freedom for chi-squared values being
      determined by the number of compartments and the number of experimental groups of
      cells. Compartmental chi-squared values making substantial contributions to the
      total chi-squared values then identify where the main between-group differences
      reside. The method requires no information about compartment size (for example,
      organelle profile area or membrane trace length) and does not even depend
      critically on standardising between-group magnification. Its application is
      illustrated using datasets from immunolabelling studies designed to localise the
      KDEL receptor, phosphatidyl-inositol 4,5-bisphosphate, GLUT4 and rab4 at the
      electron microscopic level.

PMID- 15258774
TI  - The effect of specific gravity of perfluorocarbon liquid on the retina after
      experimental vitreous substitution.
AB  - PURPOSE: To evaluate the histological changes in the retina after experimental
      vitreous substitution with various amounts of perfluorophenanthrene (PFPH).
      METHODS: Thirty-two rabbit eyes were mechanically vitrectomized and filled up
      with 0.8 cc or 0.2 cc highly purified PFPH. The substance remained for 1 week (4
      eyes), 2 weeks (8 eyes), 4 weeks (10 eyes) or 8 weeks (10 eyes). Eight eyes
      underwent the same surgical procedure without PFPH exchange to serve as a control
      group. A histological comparison of corresponding areas in the center and in the
      periphery of the inferior retina ensued. RESULTS: After 2 weeks, nuclear drop
      downs and irregularities of the outer plexiform layer and of both nuclear layers
      were observed centrally in the eyes with a 0.8 cc substitution. The changes
      proceeded to irregularities and cell loss of all retinal layers with focal areas
      of complete destruction of the retinal architecture after 8 weeks. In contrast,
      single nuclear drop-downs, wrinkling of the outer nuclear layer and cell loss in
      the photoreceptor layer were observed in the peripheral retina at the end of the
      observation period. In those eyes where 0.2 cc PFPH was exchanged nuclear drop
      downs were found after 2 weeks, leading to focal thinning of the outer plexiform
      layer and irregularities of the outer nuclear layer after 4 weeks with an
      insignificant increase after 8 weeks. At this time these histological alterations
      were comparable with those that we observed after 2 weeks in the eyes with a 0.8
      cc tamponade in a corresponding area. CONCLUSIONS: Even high purification of PFPH
      does not prevent retinal damage. The different results in different areas after
      vitreous substitution with 0.2 cc and with 0.8 cc demonstrate that the high
      specific gravity of the substance may also play a role in the development of
      histological changes after extended tamponade.

PMID- 15258775
TI  - The age-dependent decrease in the myogenic response of retinal arterioles as
      studied with the Retinal Vessel Analyzer.
AB  - PURPOSE: To study the age-dependent change in myogenic response of retinal
      arterioles. METHODS: Fifty-one healthy volunteers with at least ten persons in
      each of the five age decades (I-V) between 20 and 69 years were subjected to
      diameter measurement of retinal arterioles using the Retinal Vessel Analyzer
      (RVA) during rest and during an increase in the systemic blood pressure when
      lifting hand weights. The transmural pressure in the retinal arterioles during
      the procedures was estimated from the blood pressure and the intraocular pressure
      and was compared to the accompanying diameter response. RESULTS: The retinal
      arteriolar diameter showed a significant decrease as a function of increasing
      weight for the two younger age groups below the age of 40 years (P=0.007, group
      I, and P=0.049, group II), compatible with perfect autoregulation, whereas no
      such change was observed in persons above this age (P=0.41, 0.053, 0.29 for
      groups III-V, respectively). CONCLUSION: Studies on autoregulation in retinal
      disease should consider the normal age-related decrease in diameter response of
      retinal arterioles when the blood pressure is changed.

PMID- 15258776
TI  - Verteporfin photodynamic therapy for extrafoveal choroidal neovascularisation in
      pathologic myopia.
AB  - BACKGROUND: To report long-term functional and morphological outcome of
      verteporfin photodynamic therapy (PDT) for classic extrafoveal choroidal
      neovascularisation (CNV) secondary to pathologic myopia. METHODS: This
      retrospective case series included three eyes of three consecutive patients with
      classic extrafoveal CNV secondary to pathologic myopia, who underwent PDT at a
      tertiary retinal referral centre. Change in visual acuity and fluorescein leakage
      was the main outcome criteria. RESULTS: The patients were followed up an average
      of 36 months (33-40 months). In all eyes increase of visual acuity (one eye 1
      ETDRS line, two eyes 2 ETDRS line) and no fluorescein leakage of the CNV were
      seen. CONCLUSIONS: PDT can achieve long-term improvement of the visual acuity and
      morphological stability in selected cases with classic extrafoveal CNV in
      pathologic myopia. Large scale randomised studies are warranted for assessment of
      the benefit of PDT in such eyes.

PMID- 15258777
TI  - Aqueous humor levels of cytokines are related to vitreous levels and progression
      of diabetic retinopathy in diabetic patients.
AB  - BACKGROUND: Cytokine levels are elevated in the ocular fluid of diabetic
      patients. It is unclear whether aqueous humor levels of vascular endothelial
      growth factor (VEGF) and interleukin-6 (IL-6) are related to the vitreous fluid
      levels of these substances and to the progression of diabetic retinopathy.
      METHODS: Aqueous humor and vitreous fluid samples were obtained during cataract
      and vitreous surgery from ten eyes of ten patients with diabetic macular edema
      and 26 eyes of 26 patients with proliferative diabetic retinopathy (PDR). The
      VEGF and IL-6 levels in aqueous humor, vitreous fluid, and plasma were measured
      by enzyme-linked immunosorbent assay. RESULTS: VEGF and IL-6 levels in aqueous
      humor were significantly correlated with those in vitreous fluid (rho=0.793 and
      rho=0.737, respectively). VEGF levels in aqueous humor and vitreous fluid were
      significantly correlated with the corresponding IL-6 levels (rho=0.631 and
      rho=0.687, respectively). The aqueous and vitreous levels of VEGF were
      significantly correlated with the severity of diabetic retinopathy (rho=0.659 and
      rho=0.771, respectively). Aqueous and vitreous levels of IL-6 were also
      significantly correlated with the severity of diabetic retinopathy (rho=0.742 and
      rho=0.746, respectively). Aqueous and vitreous levels of both VEGF and IL-6 were
      significantly higher in the patients with active PDR than those in quiescent PDR.
      CONCLUSIONS: Our results suggest that there is a significant relationship between
      VEGF and IL-6 levels in aqueous humor and in vitreous fluid. Measurement of the
      aqueous levels of VEGF and IL-6 may be useful to analyze the pathogenesis of
      diabetic retinopathy and to predict disease activity.

PMID- 15258778
TI  - Subfoveal hemorrhage after verteporfin photodynamic therapy in treatment of
      choroidal neovascularization.
AB  - BACKGROUND: To identify the frequency of new subfoveal hemorrhage and its impact
      on visual acuity 2 weeks following verteporfin photodynamic therapy (PDT) in the
      treatment of predominantly classic subfoveal choroidal neovascularization (CNV)
      secondary to age-related macular degeneration (AMD). METHODS: Retrospective,
      noncomparative, consecutive, interventional case series. At a tertiary retinal
      referral center, 104 eyes of 97 consecutive patients with predominantly classic
      subfoveal CNV were treated by PDT. Morphological outcomes include new subfoveal
      hemorrhage assessed on the photo review (pretreatment, 2 and 12 weeks after PDT).
      Visual acuity outcomes include moderate (3-5 ETDRS lines) and severe (6 and more
      ETDRS lines) loss of visual acuity at 2 weeks after PDT. RESULTS: In this study,
      104 eyes of 97 patients were analyzed. CNV in all eyes was secondary to AMD. New
      subfoveal hemorrhage was found in 22% (23/104) of the eyes 2 weeks following PDT.
      17.4% (4/23) of the eyes with new subfoveal hemorrhage had moderate or severe
      loss of visual acuity. In such eyes the 12-week examination revealed considerable
      resorption of the new subfoveal hemorrhage with some improvement of visual
      acuity. CONCLUSIONS: In 3.8% of the eyes that underwent PDT for predominantly
      classic subfoveal CNV secondary to AMD, new subfoveal hemorrhage may result in
      moderate or severe loss of visual acuity within 2 weeks. In all eyes with new
      subfoveal hemorrhage, considerable resorption of the hemorrhage and some
      improvement of the visual acuity were seen at 12 weeks. Candidates for PDT should
      be informed about the low risk of this complication.

PMID- 15258779
TI  - Sleep-related non epileptic motor disorders.
AB  - Sleep-related non epileptic motor disorders represent a frequent but often
      neglected or trivialized source of neurological disability. In recent decades,
      the widespread adoption of videopolygraphic techniques has better characterized
      already known nosographic entities and described a bewildering variety of
      previously unrecognized clinical entities (such as REM sleep behaviour disorder,
      sleep-related eating disorder, benign neonatal sleep myoclonus, facio-mandibular
      myoclonus during sleep, fragmentary hypnic myoclonus, propriospinal myoclonus at
      the wake-sleep transition, rhythmic feet movements during sleep, etc). The scope
      of the neurophysiological investigations of sleep related disorders has therefore
      been much expanded. However, advances in the semeiology and clinical description
      of sleep-related movement disorders has rarely been matched by adequate
      understanding of the underlying pathophysiological mechanisms, or by major
      advances in treatment. The main sleep-related motor disorders are described here,
      following the only classification currently available, e. g. that offered by the
      International Sleep Disorders Classification of the American Sleep Disorders
      Association, which is more a classification of diseases of sleep than of movement
      disorders. The increasing use of functional neuroimaging in vivo and of updated
      neurophysiological and molecular techniques in man and in the experimental animal
      will hopefully lead to a better understanding of these disorders in terms of
      pathophysiology of disordered motor control.

PMID- 15258781
TI  - Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised
      alpha-fetoprotein.
AB  - We describe three patients from two families with progressive spinocerebellar
      ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and
      hypercholesterolaemia. Two siblings had identical clinical features, with late
      childhood onset of symptoms and slow progression, requiring crutches to walk at
      ages 37 and 38 years. Another patient developed ataxia aged 13 years and became
      wheel-chair bound by 20 years of age. Although they all had raised serum AFP
      levels, their clinical, immunological, biochemical, cytogenetic and molecular
      genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive
      investigation including imaging, biochemical and genetic studies excluded other
      known ataxias. Their clinical features most closely resemble the phenotype of a
      single consanguineous Japanese family with four individuals affected by
      spinocerebellar ataxia, peripheral neuropathy, raised AFP and
      hypercholesterolaemia. Homozygosity mapping has identified a locus in this
      Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible
      linkage to 9q34, suggesting these may be the first Caucasian families described
      with this disorder.

PMID- 15258780
TI  - Psychiatric aspects of Parkinson's disease--an update.
AB  - In patients with Parkinson's disease (PD) disturbances of mental state constitute
      some of the most difficult treatment challenges of advanced disease, often
      limiting effective treatment of motor symptoms and leading to increased
      disability and poor quality of life. This article provides an update on the
      current knowledge of these complications and the use of old and new drugs in
      their management. Mental state alterations in PD include depression, anxiety,
      cognitive impairment, apathy, and treatment-related psychiatric symptoms. The
      latter range from vivid dreams and hallucinations to delusions, manic symptoms,
      hypersexuality, dopamine dysregulation syndrome and delirium. While some of these
      symptoms may be alleviated by anti-parkinsonian medication, especially if they
      are off-period related, treatment-related phenomena are usually exacerbated by
      increasing the number or dosage of antiparkinsonian drugs. Elimination of
      exacerbating factors and simplification of drug regimes are the first and most
      important steps in improvement of such symptoms. However, the advent of atypical
      antipsychotics such as clozapine has dramatically helped the management of
      treatment-related psychiatric complications in PD. In patients with dementia
      associated with PD cognitive functioning and behavioural problems appear to
      respond to cholinesterase inhibitors, such as rivastigmine or donepezil.
      Depression is a common problem in early as well as advanced PD, and selective
      serotonin reuptake inhibitors, reboxetine, and tricyclic antidepressants have
      been reported to be effective and well tolerated antidepressants. Randomised,
      controlled studies are required to assess the differential efficacy and
      tolerability of antidepressants in patients with PD, including the newer
      antidepressants with serotonergic and noradrenergic properties.

PMID- 15258782
TI  - Frequency, timing and outcome of gastrostomy tubes for amyotrophic lateral
      sclerosis/motor neurone disease--a record linkage study from the Scottish Motor
      Neurone Disease Register.
AB  - AIMS: To describe the frequency, timing and outcome from gastrostomy in
      amyotrophic lateral sclerosis/motor neurone disease (ALS/MND). METHODS: The
      Scottish MND Register, a population based disease register (1989-1998), with
      record linkage to the Scottish Morbidity 1 dataset of hospital discharges coded
      for gastrostomy procedure was used. Descriptive statistics of patients undergoing
      gastrostomy were extracted. Survival analysis used Kaplan Meier and Cox
      proportional hazards methods. RESULTS: For patients diagnosed between 1989-98,
      142 percutaneous endoscopic gastrostomy (PEG) insertion episodes were identified
      in 1226 patients, 130 of which occurred before the censoring date of 31 December
      1999.Annually, on average, 5% of all revalent patients underwent gastrostomy, and
      this rate appeared to double between 1989-98. The cumulative incidence of
      gastrostomy was 11%. Mean age at PEG tube insertion was 66.8 years, with a mean
      disease duration of 24 months. Median survival from PEG tube insertion was 146
      days. The 1 month mortality after gastrostomy was 25%. Gastrostomy did not confer
      a survival advantage compared with no gastrostomy. CONCLUSIONS: We found that
      gastrostomy feeding tubes are being inserted more frequently in people with
      ALS/MND. An unexpectedly high early mortality was detected which probably
      reflects a lack of selection bias compared with previously published data. It is
      possible that changes in the practice of gastrostomy placement since 1998 result
      in better outcomes for patients with ALS/MND. Prospective studies are required to
      assess the risks and benefits of enteral nutrition in ALS/MND.

PMID- 15258783
TI  - Diffusion-weighted MRI of spinal cord infarction--high resolution imaging and
      time course of diffusion abnormality.
AB  - Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted
      (DW) MRI has been established as a highly sensitive technique for assessing acute
      cerebral ischemia, its role in spinal cord infarction remains to be determined.
      The purpose of this study is to present the signal characteristics of acute
      spinal cord ischemia using DWMRI within the first two days and after one week.
      MRI including DW imaging (DWI) was performed in three patients with acute spinal
      cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated
      after one week in two patients. Two initial scans included EPI DW sequences in
      transverse and sagittal orientation. The remaining examinations were performed
      with an optimised high-spatial resolution DWI sequence in the transverse plane.
      The diagnosis of spinal cord ischemia was established by imaging, clinical
      history and CSF analysis. T2 signal abnormality and restricted diffusion was
      demonstrated in all initial examinations. Transverse DW sequences had the highest
      sensitivity. The spinal infarctions were mainly located in the centre of the
      spinal cord and the grey matter. Contrast enhancement was absent. After one week,
      the restricted diffusion had normalised (pseudo normalisation) whereas the T2
      signal changes had become more prominent. Restricted diffusion in the course of
      spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a
      diffusion abnormality can be found after few hours, it does not last for longer
      than one week. At this time, the establishment of the diagnosis has to rely
      mainly on T2-weighted images with additional post contrast T1-weighted images
      being useful.

PMID- 15258784
TI  - Cerebral microembolism during transcatheter closure of patent foramen ovale.
AB  - BACKGROUND: Although transcatheter closure of patent foramen ovale (PFO) and
      atrial septal defect (ASD) has become a commonly performed intervention, the
      incidence of cerebral embolism with or without neurological deficits during such
      procedures has not been studied. METHODS: We monitored the middle cerebral artery
      in two different depths (48 mm and 53 mm) by continuous transcranial Doppler
      ultrasound during transcatheter PFO closure in 35 consecutive patients (F/M
      20/15, mean age 47 +/- 11 years) and during ASD closure in 8 patients (F/M 7/1,
      mean age 45 +/- 5 years). All automatically detected high intensity transient
      signals (HITS) were manually reviewed to eliminate artifacts. RESULTS: HITS were
      detected in 33 of 35 patients (96%) with a median rate of 8 (interquartile range
      4-19, range 2-29) HITS. The highest rates were observed when the septum was
      crossed with the guide wire (median 2; IQR 0-12; range 0-25) and when the left
      atrial disc was deployed (median 2; IQR 1-4; range 0-13). Despite this high rate
      of cerebral microembolism no clinically apparent neurological or
      neuropsychological deficit was observed. CONCLUSIONS: Silent cerebral embolism
      frequently occurs during transcatheter PFO and ASD closure. The peak of HITS at
      the time of crossing the septum with the guide wire may support the hypothesis
      that cerebral emboli in patients with PFO may originate from the septum itself.
      This may represent an alternative mechanism to the generally assumed paradoxical
      embolism.

PMID- 15258785
TI  - Symptomatic human neurocysticercosis--age, sex and exposure factors relating with
      disease heterogeneity.
AB  - OBJECTIVE: To evaluate the relevance of exposure and host biological factors in
      the heterogeneity of the clinical, radiological and inflammatory picture of
      neurocysticercosis (NCC). METHODS: 105 Mexican symptomatic NCC patients confirmed
      by imaging were studied before they received any specific treatment. The
      relationships studied were those between a) the patients' characteristics
      (gender, age and level of exposure), b) the type of clinical picture and c) the
      radiological and inflammatory characteristics of the disease (number, aspect,
      localization of the parasites, and CSF leukocyte counts). RESULTS: Seizures were
      the most frequent symptom and multiple subarachnoid cysticerci the most frequent
      localization. Symptomatology related to the developmental stage, number and
      localization of the parasites as well as the CSF leukocyte-counts. The total
      number of cysticercal lesions and of vesicular cysticerci increased with
      age,whereas the number of colloidal cysticerci decreased. CSF leukocyte-counts
      were higher in women than in men. Levels of exposure did not correlate with the
      clinical and radiological pictures. CONCLUSIONS: The variability found in the
      number, stage, localization and inflammation in the parasite lesions is strongly
      associated with the heterogeneity of NCC symptoms. The increased number of
      vesicular cysticerci and the decreased number of degenerating cysticerci with
      aging, as well as the prominence of inflammation in women suggest that immuno
      endocrinological factors may play a role in susceptibility and pathogenesis. The
      data also show that with increasing age and exposure there is no increment in
      severity, a suggestion that there might be ways of regulating pathogenicity.

PMID- 15258786
TI  - Gender-specific risk of perioperative complications in carotid endarterectomy
      patients with contralateral carotid artery stenosis or occlusion.
AB  - Carotid endarterectomy (CEA) has been shown to be effective in stroke prevention
      in selected patients. Some studies, however, identified gender as an independent
      risk factor for perioperative CEA complications demonstrating an increased rate
      of perioperative stroke or death in women. Furthermore, contralateral internal
      carotid artery (ICA) occlusion has been associated with higher rates of
      perioperative CEA complications. Therefore, we sought to analyse the gender
      specific risk of perioperative CEA complications between patients with or without
      contralateral ICA stenosis or occlusion. We retrospectively analysed 212
      consecutive CEA patients (male = 156, Female = 56) for their gender-specific,
      perioperative risk of stroke, transient ischemic attack (TIA), restenosis and
      cardiac complications in the presence (62%) or absence (38%) of a contralateral
      ICA stenosis/occlusion. In women but not in men, risk of perioperative ischemic
      events (stroke, TIA) or re-stenosis (p = 0.036) and combined perioperative
      complications (ischemic events, re-stenosis or cardiac complications; 38.2 % vs.
      9.1%; p = 0.028) was significantly increased in the presence of a contralateral
      ICA stenosis or occlusion. Furthermore, in the presence of a contralateral ICA
      stenosis/occlusion the number of perioperative ischemic events (p = 0.008) and
      combined perioperative complications (38.2 % vs. 14.3%; p = 0.006) was
      significantly higher in female than in male patients. Our study suggests that
      women with contralateral ICA stenosis or occlusion may have a significantly
      higher risk for perioperative CEA complications than other subgroups of CEA
      patients. This risk increase seems to be gender-specific and, if confirmed in
      larger prospective studies, may influence ICA stenosis therapy in the presence of
      a contralateral ICA stenosis/occlusion in female patients.

PMID- 15258787
TI  - Familial adolescent-onset scoliosis and later segmental dystonia in an Irish
      family.
AB  - Adolescent-onset scoliosis occurs more frequently than expected in primary adult
      onset cervical dystonia and a genetic association between the conditions has been
      postulated. The authors report a family in which four members have adult-onset
      cervical and/or brachial dystonia, two of whom have coexistent scoliosis. Four
      other individuals have isolated childhood- or adolescent-onset scoliosis.
      Adolescent-onset scoliosis may represent part of the dystonia phenotype in this
      family.

PMID- 15258788
TI  - Hereditary haemochromatosis is unlikely to cause movement disorders--a critical
      review.
AB  - Hereditary haemochromatosis (HH) is a common autosomal recessive systemic iron
      overload disorder in which CNS manifestations, particularly movement disorders,
      have been reported. We report a 63-year-old woman with familial HH with a four
      year history of progressive gait disturbance, chorea, and mild cervical and
      laryngeal dystonia. Her movement disorder was thought to be related to the
      haemochromatosis. On further investigation, analysis for the Huntington's disease
      expansion was positive. A review of the seven published cases of movement
      disorders associated with HH as well as data concerning brain iron deposition in
      this condition leads us to debate the causal link between movement disorders and
      HH. We suggest that movement disorders are rare in association with HH, and that
      such patients should be thoroughly investigated for another cause for their
      movement disorder.

PMID- 15258789
TI  - Lack of association between polymorphisms of the toll-like receptor 4 gene and
      cerebral ischemia.
AB  - Toll-like receptor-4 (TLR4), an important mediator of the innate immune response,
      is expressed in atherosclerotic lesions. The common single nucleotide exchange
      (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function
      and to be associated with a decreased risk of carotid atherosclerosis. Therefore,
      we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral
      ischemia. We studied the prevalence of two common polymorphisms of the TLR4 gene
      (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross
      sectional study including 769 patients either with type 1 or type 2 diabetes
      mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a
      case-control study (study 2) including 128 consecutive patients with cerebral
      ischemia, mean age 60 +/- 10.9 years and 139 control subjects, and (3.) a case
      control study (study 3) including 171 young adults aged < 50 years with cerebral
      ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile
      were detected by restriction length analysis. The prevalence of the TLR4
      genotypes was essentially the same between patients with cerebral ischemia and
      control subjects in all 3 study populations. Furthermore, there was also no
      association with the subgroup of atherosclerotic stroke in both case-control
      studies populations. Although TLR4 polymorphisms are associated with a decreased
      risk of carotid atherosclerotic lesions, our findings indicate that they do not
      influence the prevalence of cerebral ischemia. This implies that the Asp299Gly
      TLR4-allele might have a protective role in carotid atherosclerosis, but not in
      cerebral ischemia.

PMID- 15258790
TI  - The long-term outcome of anti-Jo-1-positive inflammatory myopathies.
AB  - OBJECTIVE: To determine the response to treatment and the long-term outcome of
      patients with the antisynthetase syndrome associated with anti-Jo-1-antibodies.
      PATIENTS AND METHODS: A total of 12 patients with histologically proven myositis
      and anti-Jo-1-autoantibodies were evaluated over a mean follow-up period of 66.4
      months. In all patients neuromuscular function tests, electromyographic
      examinations, pulmonary function tests and high-resolution-computed tomography of
      the lungs were performed regularly. RESULTS: Muscle function improved in all
      patients with treatment, and a complete clinical response was achieved in 5
      patients. Pulmonary function worsened in 1 patient, who died from respiratory
      failure, but normalised in 4 patients. Arthropathy progressed despite improvement
      of myositis and pulmonary status in 2 patients. Discontinuation of treatment was
      facilitated in 1 patient, although long-term therapy was required in 10 patients.
      In 2 patients with refractory disease, treatment with intravenous immunoglobulins
      was successful. Severe side effects of treatment occurred in 7 patients and
      overall mortality rate was one of 12 (8 %). CONCLUSION: The antisynthetase
      syndrome associated with anti-Jo-1-antibodies requires long-term
      immunosuppressive therapy in most patients. Whereas a complete clinical response
      of muscular symptoms is frequent, continued deterioration of the pulmonary system
      may occur despite immunosuppressive treatment, and may lead to fatal outcome. An
      interdisciplinary therapeutic approach is necessary for best possible results in
      these patients.

PMID- 15258791
TI  - Emotional incontinence in Chinese stroke patients--diagnosis, frequency, and
      clinical and radiological correlates.
AB  - Of the few studies published on poststroke emotional incontinence (PSEI), none
      has investigated a consecutive stroke cohort in a Chinese patient population. The
      objective of this study was to examine the frequency and the clinical and
      radiological correlates of PSEI in Chinese stroke patients in Hong Kong. Three
      months after their admission, a psychiatrist interviewed 127 stroke patients who
      were consecutively admitted to the medical wards of a university-affiliated
      regional hospital. The presence of PSEI was defined according to both Kim's and
      House's criteria. The frequency of PSEI was 17.9% according to Kim's criteria and
      6.3% according to House's criteria. The kappa between the two sets of criteria
      was 0.34. Univariate analysis found that PSEI was associated with a younger age,
      previous history of depression, a higher National Institute of Health Stroke
      Scale total score and cortical infarcts. Multivariate logistic regression
      suggested that past history of depression and cortical infarcts were independent
      predictors for PSEI. In conclusion, PSEI is relatively common among Chinese
      stroke survivors. A previous history of depression or cortical lesions were
      independent predictors for PSEI. There is a need for a revision of the diagnostic
      criteria for PSEI.

PMID- 15258792
TI  - Marked increase of beta-amyloid(1-42) and amyloid precursor protein in
      ventricular cerebrospinal fluid after severe traumatic brain injury.
AB  - Severe traumatic brain injury (TBI) may result in widespread damage to axons,
      termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by
      synaptic and axonal degeneration together with senile plaques (SP). SP are mainly
      composed of aggregated beta-amyloid (Abeta), which are peptides derived from the
      amyloid precursor protein (APP). Apart from TBI in itself being considered a risk
      factor for AD, severe head injury seems to initiate a cascade of molecular events
      that are also associated with AD. We have therefore analysed the 42 amino acid
      forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP)
      in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28
      patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss
      sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a
      significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to
      day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11.
      There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1
      to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged
      after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta
      expression may occur as a secondary phenomenon after TBI with axonal damage. The
      unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF
      Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42)
      does not reflect Abeta metabolism in the central nervous system (CNS).

PMID- 15258793
TI  - Peripheral neuropathy in HTLV-I infected individuals without tropical spastic
      paraparesis/HTLV-I-associated myelopathy.
AB  - Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the
      classical neurological manifestation of HTLV-I. Only a few studies have described
      isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335
      infected individuals without TSP/HAM were evaluated for the presence of PN and 45
      of them showed evidences of peripheral nervous system involvement. Of these 21
      patients had isolated PN, defined by clinical and/or electrophysiological
      criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal
      degeneration in 2 and segmental demyelination in 1. Therefore, peripheral
      neuropathy can be found as an isolated manifestation of HTLV-I infection. We
      conclude that HTLV-I infection should be investigated in patients with PN of
      unknown origin.

PMID- 15258794
TI  - Transient monocular blindness: the controversial role of the ophthalmic artery-
      response to Rutgers et al. in J Neurol (2003) 250:501-502.

PMID- 15258796
TI  - Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to
      hypothalamic lesion in a case of multiple sclerosis.

PMID- 15258797
TI  - Are vigabatrin-associated visual field constrictions asymptomatic?

PMID- 15258798
TI  - Viper snakebite causing symptomatic intracerebral haemorrhage.

PMID- 15258799
TI  - Comment on "The codon 129 polymorphism of the prion protein gene influences
      earlier cognitive performance in Down syndrome subjects"--by Del Bo et al. in J
      Neurol (2003) 250:688-692.

PMID- 15258800
TI  - Spectral analysis of heart rate variability in multiple system atrophy and
      unexplained sporadic ataxia.

PMID- 15258801
TI  - Basal ganglia involvement of a patient with SCA 17--a new form of autosomal
      dominant spinocerebellar ataxia.

PMID- 15258803
TI  - Bernard Brouwer (1881-1949).

PMID- 15258802
TI  - Miller Fisher syndrome--a presenting clinical manifestation of lung cancer in a
      previously apparently healthy individual.

PMID- 15258806
TI  - Genomic instability in both wild-type and telomerase null MEFs.
AB  - To examine chromosome instability in the absence of telomerase, we established
      mouse embryonic fibroblast (MEF) lines from late generation mTR-/- and wild-type
      animals and examined metaphases using telomere fluorescence in situ hybridization
      (FISH) and spectral karyotyping (SKY). In early passages, mTR-/- G6 cell lines
      showed more chromosome ends with no telomere signal, more chromosome end-to-end
      fusions and greater radiosensitivity than wild-type lines. At later passages,
      however, the rate of genomic instability in the wild-type MEFs increased to a
      level similar or higher than seen in the mTR-/- G6 cell lines. This high degree
      of instability in wild-type MEF lines suggests that post-crisis MEFs should not
      be considered genetically defined cell lines. Surprisingly, the increased
      radiosensitivity seen in early passage mTR-/- G6 cultures was lost after crisis.
      Both post-crisis mTR-/- G6 MEFs and wild-type MEFs showed loss of p53 and gamma
      H2AX phosphorylation in response to irradiation, indicating a loss of DNA damage
      checkpoints.

PMID- 15258807
TI  - Coding properties of Oxytricha trifallax (Sterkiella histriomuscorum)
      macronuclear chromosomes: analysis of a pilot genome project.
AB  - The macronuclear genomes of spirotrichous ciliates are almost entirely polyploid,
      single-gene chromosomes ("nanochromosomes"). We recently performed a pilot genome
      project for a member of this group, Oxytricha trifallax ( Sterkiella
      histriomuscorum), in which approximately 2000 nanochromosomes were cloned at
      random and end-sequenced. Here we describe the global properties of the coding
      regions predicted for these molecules, including nucleotide composition, codon
      usage, and intron properties. In identifying splice donor, acceptor and branch
      sites, we found that longer introns in Oxytricha have a stronger signal at the
      donor site than do smaller introns, as has been found for Caenorhabditis elegans
      and Drosophila, despite the overall small size of the introns. A systematic
      search for multi-gene chromosomes identified 11 candidate nanochromosomes. We
      compare the results from this large dataset with those obtained from earlier
      studies and with statistics recorded from ciliates and other eukaryotes.

PMID- 15258808
TI  - The centromeric regions of potato chromosomes contain megabase-sized tandem
      arrays of telomere-similar sequence.
AB  - Telomere-similar sequences have been found in non-telomeric regions in various
      eukaryotic species. Centromeric regions often harbor such interstitial telomeric
      repeats (ITRs). We isolated a 2.8 kb ITR, pSbTC1, in a diploid potato species
      Solanum bulbocastanum. DNA sequences related to the pSbTC1 family are widely
      distributed in different Solanum species. The pSbTC1-related sequences are
      organized into tandem arrays and located mainly in the centromeric regions of
      potato chromosomes. Most notably, the pSbTC1-related sequences have undergone
      extensive amplification and a single array can span up to multiple megabases.
      These results suggest that the pSbTC1-related sequences are not simple relics of
      ancient events in karyotype evolution, such as chromosomal fusions. We also
      demonstrated that the pSbTC1-related sequences are heavily methylated and are
      associated with highly condensed centromeric heterochromatin.

PMID- 15258810
TI  - An unusual presentation of neck dermoid cyst.
AB  - Congenital masses are the most common non-inflammatory neck lesions in children.
      Although usually present at birth, they can appear at any age. Dermoid cysts are
      benign lesions of congenital origin usually presenting as a midline neck mass.
      They rarely appear in the lateral region of the neck. Lateral cervical dermoid
      cyst is presented as a rare, unusual case, and differential diagnosis and
      management are discussed in light of recent literature.

PMID- 15258809
TI  - The Nijmegen breakage syndrome gene and its role in genome stability.
AB  - NBS1 is the key regulator of the RAD50/MRE11/NBS1 (R/M/N) protein complex, a
      sensor and mediator for cellular DNA damage response. NBS1 potentiates the
      enzymatic activity of MRE11 and directs the R/M/N complex to sites of DNA damage,
      where it forms nuclear foci by interacting with phosphorylated H2AX. The R/M/N
      complex also activates the ATM kinase, which is a major kinase involved in the
      activation of DNA damage signal pathways. The ATM requires the R/M/N complex for
      its own activation following DNA damage, and for conformational change to develop
      a high affinity for target proteins. In addition, association of NBS1 with PML,
      the promyelocytic leukemia protein, is required to form nuclear bodies, which
      have various functions depending on their location and composition. These nuclear
      bodies function not only in response to DNA damage, but are also involved in
      telomere maintenance when they are located on telomeres. In this review, we
      describe the role of NBS1 in the maintenance of genetic stability through the
      activation of cell-cycle checkpoints, DNA repair, and protein relocation.

PMID- 15258811
TI  - Histological features and malignant transformation of inverted papilloma.
AB  - Inverted papilloma (IP) is a primarily benign epithelial neoplasm with a
      propensity to transform to squamous cell carcinoma (SCC). Neither the etiology of
      IP nor the factors responsible for malignant transformation are fully known to
      date. A considerable number of histopathological grading systems have been
      suggested. It was the aim of this study to find histological parameters in IP
      that allow a prognosis concerning the occurrence of malignant transformation. In
      a group of 93 cases of IP, the patients' records, histological specimens and a
      questionnaire were evaluated. Thirteen patients had suffered a recurrence of a
      previously treated IP. SCC in the IP had been diagnosed in 12 of the cases. The
      histological specimen showed increased counts of mitosis and dyscariosis in the
      IP. All other histological parameters did not show a significant difference
      between the groups. History and symptoms proved to be nonspecific as well.
      Patients in the group with SCC were significantly older at the first diagnosis of
      IP than patients without carcinoma. This group also included a higher portion of
      male patients. Patients fulfilling the named histological criteria combined with
      male gender and higher age are a high-risk group in the necessary long-term
      follow-up.

PMID- 15258812
TI  - Inverted malignant pilomatricoma of the neck.
AB  - Malignant pilomatricoma is an uncommon malignant follicular adnexal tumor with a
      predilection for the head and neck among older males. We report the case of a
      male with an inverted malignant pilomatricoma of the left neck. The initial
      diagnostics and the treatment pointed to carcinoma of unknown primary (CUP
      syndrome). The preoperative diagnostic tests included ultrasound examination, CT
      scan and fine-needle aspiration cytology. However, the preoperative diagnostics
      did not provide any further information, leading to doubts concerning the
      initially proposed diagnosis. Histology of the resected tumor revealed a
      malignant pilomatricoma. We report the clinical presentation and the management
      of this case and discuss the clinical and histological findings.

PMID- 15258813
TI  - Long-term disease-free survival effected by gemcitabine in a heavily pretreated
      patient with recurrent ovarian carcinoma.
AB  - INTRODUCTION: Gemcitabine has been shown to have modest activity and low and well
      tolerated toxicity in heavily pretreated patients with recurrent ovarian
      carcinoma. CASE REPORT: A 46-year-old patient with recurrent ovarian carcinoma
      who failed with two previous lines of chemotherapy has for the last 40 months
      received third-line chemotherapy with gemcitabine. This has resulted in an
      extraordinary long-term disease-free survival of 38 months. Toxicity has been low
      and well tolerated. CONCLUSION: Gemcitabine seems to be an attractive agent for
      salvage chemotherapy in ovarian carcinoma patients who failed with prior lines of
      chemotherapy.

PMID- 15258814
TI  - Successful and safe treatment of hypertrichosis by high-intensity pulses of
      noncoherent light in a patient with hepatoerythropoietic porphyria.
AB  - Hypertrichosis is a common feature in cutaneous porphyrias, characterized by high
      accumulation of photoreactive porphyrins. Photothermolysis induced by noncoherent
      light (755-1200 nm) and energy fluence of 42 J/cm(2) was applied to a patient
      with hepatoerythropoietic porphyria. Hypertrichosis was almost completely removed
      after seven sessions without development of skin lesions.

PMID- 15258816
TI  - Pulmonary metastasectomy for pediatric solid tumors.
AB  - Most pediatric thoracic malignancy is pulmonary disease secondary to solid tumors
      of childhood. The management of isolated pulmonary metastases in adulthood is
      well documented. Little has been published to document the long-term outcome of
      pulmonary metastasectomy in childhood. A retrospective study was undertaken to
      assess the results of surgery for isolated pulmonary metastases. Twenty children
      underwent surgery over 12 years (mean follow-up 8 years). Five had Wilms' tumor
      (mean age 51 months), eight had osteogenic sarcoma (mean age 141 months), three
      had rhabdomyosarcoma (mean age 92 months), two had hepatoblastoma (mean age 30
      months) and two had teratoma (mean age 72 months). Four had bilateral synchronous
      metastases and thoracotomies, and one had bilateral metachronous metastases and
      thoracotomies. Nineteen children were discharged well within 10 days of surgery.
      There was one early complication: a death due to pneumonia. Four children
      subsequently died postoperatively with cranial metastases (mean 29 months
      postoperatively). The remaining 16 children remain alive and well. As part of the
      combined therapy, these results would support an aggressive surgical approach to
      this disease. Preoperative assessment should include contrast enhanced computed
      tomogram of the head and chest as well as chest X-ray taken immediately
      preoperatively to exclude metastases. Bilateral synchronous and metachronous
      thoracotomy is well tolerated in childhood.

PMID- 15258817
TI  - The evolution of stereotactic guidance in neuroendoscopy.
AB  - OBJECTIVES: To evaluate the advantages and limitations of the utilized system in
      accordance with the operative indications of stereotactic neuroendoscopy.
      PATIENTS AND METHODS: We reviewed our collective experience of computer-assisted
      stereotaxy (frame-based and frameless) and virtual endoscopy in neuroendoscopic
      surgery from 1982 to 2003. Sterotactic guiding systems (frame-based and
      frameless) have been used to perform more than 450 neuroendoscopic operations at
      our institute. RESULTS: Even though image guidance is not essential in all cases,
      technological developments have definitely been one of the major factors in
      improving outcomes. Planning endoscopic trajectory and intraoperative orientation
      within the ventricular system or other cavities are the main indications for its
      application. CONCLUSIONS: No surgical tool, no matter how accurate, can be a
      substitute for thoughtful and methodical pre-operative planning. Image-guided
      technologies are applied in order to make endoscopic surgery safer, faster and
      more easily reproducible. Despite the high initial cost of the equipment, overall
      expenses are expected to be reduced because of greater operative efficiency and
      shorter hospital stay.

PMID- 15258818
TI  - The separation of Guatemalan craniopagus twins.
AB  - CASE REPORT: The particularities of the surgical procedure for the separation of
      craniopagi twins performed at UCLA in 2002 are presented. The main difficulty for
      the neurosurgeons was that the twins shared a common sagittal sinus and that one
      of the sisters had a poorly developed collateral venous system, thus anticipating
      a set of postoperative clinical problems. During surgery, the response of the
      brain to the progressive occlusion of the venous bridges was monitored with EEG
      and Doppler ultrasound. One of the sisters had a large intracerebral hematoma
      that was evacuated and later developed hydrocephalus, which was treated with a
      ventriculoperitoneal shunt. OUTCOME: One of the sisters had a basically
      uneventful recovery while the other contracted E. coli meningitis 8 months after
      surgery, thus impairing her motor and cognitive development. DISCUSSION: The
      details and intricacies of the anesthesia and plastic surgery are also outlined.

PMID- 15258819
TI  - Ethics and conjoined twins.
AB  - INTRODUCTION: The birth of live conjoined twins in a community can draw
      considerable attention to the appropriate ethical issues. DISCUSSION: The
      management requires the skills of a multi-disciplinary team of clinicians who
      have seldom faced the challenge. The team leader must draw together principles of
      a medical, social, cultural, religious and legal nature in reaching the best
      outcome. Often the basic question is whether one child should die or both? At
      times the question is raised whether it is justifiable to sacrifice one life to
      save the other. In these days of high technology, surgeons can be tempted to go a
      bridge too far. In reaching this decision there can be numerous hidden conflicts
      of interest. Increasingly the final decision needs to be made and approved by the
      courts so as to protect the rights of the twins and to ensure surgical
      intervention is not an unlawful act.

PMID- 15258820
TI  - [Blinking activity during visual display terminal work. Part 1: Ocular discomfort
      and pathophysiological principles].
AB  - Up to three-fourths of visual display operators complain about ocular discomfort
      after lengthy work at a monitor. The increase of displays at work has resulted in
      a problem area with growing impact for the economy and healthcare. Symptoms
      overlapping the complaints of dry eye disease point to the joint
      pathophysiological origin. In numerous studies the drastic decrease in blinking
      frequency was shown to be an essential cause of dry eye symptoms. Lid movements
      not only have the purpose of smoothing the precorneal tear film ("windshield
      effect"), but also affect the composition and stability of the different layers.
      Unfortunately, previous work has often been limited by the heterogeneity of
      measurement settings, leading to inconsistent results.

PMID- 15258821
TI  - MR imaging of gastric cancer in vitro: accuracy of invasion depth diagnosis.
AB  - The purpose of this study was to evaluate the accuracy of grading cancerous
      invasion of the gastric wall in vitro using magnetic resonance (MR) imaging.
      Twelve specimens of gastric carcinoma were examined at 1.5-T using a small, loop
      surface coil. They were imaged within 2 days of fixation in formalin. The field
      of view was 30 mm; the matrix size was 256x256, and the section thickness was 2
      mm. T1-weighted, T2-weighted and short inversion time inversion recovery (STIR)
      images were obtained. Two radiologists evaluated the MR images independently, and
      in discrepant cases, consensus was obtained through discussion. Findings on MR
      images were compared with histopathologic findings. All T1-weighted, T2-weighted
      and STIR images depicted the normal gastric wall as consisting of six layers.
      STIR images depicted normal six layers most clearly. Histologically, the
      cancerous invasion was found to extend into the mucosa in 4 of the 12 specimens,
      the submucosa in 3, the muscularis propria in 2, the subserosa in 2 and the
      serosa in 1. The grading by MR imaging matched the histopathologic findings for
      all 12 tumors. The overall accuracy was 100%. Thus, MR imaging in vitro was
      sufficiently accurate for grading cancerous invasion of the gastric wall.

PMID- 15258822
TI  - Four-dimensional volume contrast ultrasound imaging of the gallbladder compared
      with tissue harmonic imaging: preliminary experience.
AB  - Comparison of volume contrast US imaging with tissue harmonic imaging for the
      evaluation of gallbladder lesions and determination of the adequate slice
      thickness in volume contrast US imaging were performed. Forty-one patients who
      had gallbladder lesions (polyps in 26, stones in 12, and sludge in 3) were
      enrolled in our study. A Voluson 730 Expert US scanner was used throughout.
      Volume contrast US imaging with slice thicknesses of 3, 5, 10 and 15 mm and
      tissue harmonic imaging of the gallbladder were obtained. Two abdominal
      radiologists reviewed the masked images and graded by consensus these images
      using a five-point scale [from grade 1, (best), to grade 5, (worst)], based on
      the sharpness of the anterior gallbladder wall, internal artifact, lesion
      conspicuity and acoustic shadowing from stone. Volume contrast US imaging with
      thin slice thicknesses (3 or 5 mm) was judged superior to both tissue harmonic
      imaging and with thick slice thicknesses (10 or 15 mm), with respect to the
      sharpness of the anterior wall and lesion conspicuity ( P<0.001). In terms of
      internal artifact, volume contrast imaging with thin slice thicknesses was
      significantly superior to both tissue harmonic imaging and volume contrast
      imaging with a 15 mm thickness ( P<0.001) and was judged to be marginally better
      than with a 10 mm thickness ( p>0.01). With regard to acoustic shadowing, volume
      contrast imaging with thin slice thicknesses was also significantly better than
      with thick slice thicknesses ( P<0.01), and it was also marginally better than
      tissue harmonic imaging ( P>0.01). Volume contrast US imaging with thin slice
      thicknesses provides a better image quality with fewer artifacts than three other
      types of images for the evaluation of gallbladder diseases.

PMID- 15258824
TI  - Sonoanatomy of the ulnar nerve in the cubital tunnel: a multicentre study by the
      GEL.
AB  - The objective is to determine the normal appearance of the ulnar nerve on a
      posterior axial sonogram section of the elbow through the medial epicondyle and
      the humeroulnar joint space. Ultrasound evaluation was carried out on 400 elbows
      with measurement of the ulnar nerve cross-sectional area and ulnar nerve-cortex
      distance, as well as recording of apparent ulnar nerve division. Factors that
      significantly influenced the study variables were sought by statistical analysis.
      Mean cross-sectional area of the ulnar nerve at the elbow was 7.9 +/- 3.1 mm2
      overall. Values were lower in females than in males and increased between 40 and
      60 years of age. The ulnar nerve-cortex distance was 0.8 +/- 0.4 mm and varied
      widely across individuals. Apparent ulnar nerve division at the elbow was noted
      in about one-fifth of individuals, with no difference between females and males
      or between the right and left elbows. When present, apparent division was often
      bilateral and was not associated with changes in cross-sectional area or in
      distance from the medial epicondyle cortex. This study provides normative data on
      ulnar nerve sonoanatomy at the elbow and establishes that apparent ulnar nerve
      division at the elbow is a normal variant.

PMID- 15258823
TI  - Assessment of ventricular function and mass by cardiac magnetic resonance
      imaging.
AB  - Cardiac magnetic resonance imaging is currently the technique of choice for
      precise measurements of ventricular volumes, function and left ventricular (LV)
      mass. The technique is 3D and hence independent of geometrical assumptions; this,
      along with its excellent definition of endocardial and epicardial borders, makes
      it highly accurate and reproducible. Cardiac magnetic resonance (CMR) is
      particularly useful in research, as it is highly sensitive to small changes in
      ejection fraction and mass, and only a small number of subjects are required for
      a study. The excellent reproducibility makes temporal follow-up of any individual
      patient in the clinical setting a realistic possibility. This review examines the
      merits of CMR and describes the techniques used.

PMID- 15258826
TI  - Computed tomographic appearance of urachal adenocarcinomas: review of 25 cases.
AB  - Twenty-five cases of surgically proven urachal carcinomas were retrospectively
      reviewed. The radiological archives at the Armed Forces Institute of Pathology
      were searched for cases of surgically proven urachal carcinomas that had a
      computed tomographic (CT) scan as a part of their radiologic evaluation. CT
      images from all cases were evaluated to determine tumor morphology, presence and
      localization of calcification, extent of bladder invasion and metastases. Tumor
      size at presentation averaged 6 cm. Twenty-one of 25 (84%) were mixed cystic
      solid lesions and 4/25 (16%) were completely solid. Calcifications were present
      in 18/25 (72%), with 11 peripherally located, 3 central only and 4 both. Bladder
      wall invasion was present in 23/25 (92%), but was seen as an intraluminal mass in
      only 13/25 (52%). The bulk of the mass was extravesicular in 22/25 (88%).
      Metastases were present in 12/25 (48%). Our series supports observations from
      other smaller series that a midline, calcified, supravesicular mass is highly
      suspicious, if not pathognomonic, for urachal carcinoma.

PMID- 15258825
TI  - Magnetic resonance angiography virtual endoscopy in the assessment of pulmonary
      veins before radiofrequency ablation procedures for atrial fibrillation.
AB  - Magnetic resonance angiography (MRA) is a safe and non-invasive imaging method
      that can readily depict the pulmonary veins (PV), whose imaging has acquired
      momentum with the advent of new techniques for radiofrequency ablation of atrial
      fibrillation (AF). We evaluated whether virtual endoscopy from 3D MRA images (MRA
      VE) is feasible in studying the morphology of PV. Fifty patients with AF
      underwent pre-ablative MRA (1.5 T). Images were acquired with axial T-2 weighted
      and 3D-SPGR sequences after intravenous administration of Gd-DTPA and automatic
      triggering. Postprocessing was performed by an experienced radiologist with
      maximum intensity projection (MIP) and virtual endoscopy software (Navigator,
      GEMS). The venoatrial junction was visualized with MRA-VE in 49 of 50 patients
      (98.0%). Twenty-seven patients (55.1%) had two ostia on both sides, 13 patients
      (26.5%) had two ostia on the right and a single common ostium on the left, 5
      patients (10.2%) had accessory PV and 4 patients (8.2%) had both an accessory
      right PV and a single common ostium on the left. Flythrough navigation showed the
      number and spatial disposition of second-order PV branches in 48 out of 49
      patients (98.0%). MRA-VE is an excellent tool for at-a-glance visualization of
      ostia morphology, navigation of second-generation PV branches and easy
      endoluminal assessment of left atrial structures in pre-ablative imaging.

PMID- 15258827
TI  - Effect of new manganese contrast agent on tissue intensities in human volunteers:
      comparison of 0.23, 0.6 and 1.5 T MRI, a part of a phase I trial.
AB  - To evaluate the effect of a new oral manganese contrast agent (CMC-001) on
      magnetic resonance imaging (MRI) intensities at different magnetic field
      strengths. Twelve healthy volunteers underwent abdominal MRI 1 week before and
      within 2.5-4.5 h after CMC-001 (MnCl(2) and absorption promoters dissolved in
      water) intake at three different MR scanners of 0.23, 0.6 and 1.5 T. Image
      contrast and intensity enhancement of liver and pancreas were analysed relatively
      to muscle and fat intensities. Manganese blood levels were followed for 24 h.
      Whole-blood manganese concentration levels stayed within the normal range. The
      liver intensities on T2w images decreased about 10% for the 1/2 contrast dose and
      about 20% for the full contrast dose independent of the field strength. The liver
      intensities on T1w images increased more than 30% for 1/2 contrast dose and over
      40% for full contrast dose. The maximum T1 enhancement was achieved at the
      highest field. Pancreas intensities were not affected. Contrast between liver,
      muscle and fat intensities increased with magnetic field, as well as standard
      errors of the volunteer-averaged intensities. Oral intake of CMC-001 influences
      liver intensities and does not affect pancreas intensities at different magnetic
      field strengths.

PMID- 15258829
TI  - Zooidogamy in the Late Permian genus Glossopteris.
AB  - We describe details of anatomically preserved fossil glossopterid ovules from the
      Late Permian of Queensland, Australia, that contain several pollen tubes at
      various stages of releasing flagellated sperm. Each sperm is approximately 12.7
      microm long and 13.9 microm wide, with a conspicuous spiral structure comprised
      of a series of dots that resemble the position of basal bodies of flagella
      aligned along the multilayered structure (MLS). This configuration is similar to
      the helically arranged flagella in the sperm of cycads, Ginkgo, and many
      pteridophytes. However, the motile gametes of Glossopteris are considerably
      smaller than those of Ginkgo and cycads, and more similar in size, number of
      basal bodies, and number of gyres in their helix to pteridophyte forms.
      Glossopteris thus shares the intermediate stage of motile male gamete formation
      and apparently that of haustorial pollen tubes with cycads and Ginkgo.

PMID- 15258828
TI  - Regulated expression of green fluorescent protein in Debaryomyces hansenii.
AB  - The broad range of environmental conditions under which Debaryomyces hansenii can
      grow, and its production of lipolytic and proteolytic enzymes, have promoted its
      widespread use. The present work represents a preliminary characterization of D.
      hansenii for heterologous expression and secretion of green fluorescent protein
      (GFP). Six heterologous expression vectors were used to address protein
      production efficiency under regulated expression conditions. Protein expression
      in D. hansenii seems to be similar to that in Saccharomyces cerevisiae, with
      transcription being controlled by almost all of the S. cerevisiae and D. hansenii
      inducible promoters tested, with the exception of the alcohol dehydrogenase 2
      gene promoter from S. cerevisiae. Extracellular protein levels in D. hansenii
      were lower than in S. cerevisiae when Saccharomyces signal peptides were used.

PMID- 15258830
TI  - Psoas abscess in patients infected with the human immunodeficiency virus.

PMID- 15258831
TI  - In vitro activity of voriconazole and other antifungal agents against clinical
      isolates of Candida glabrata and Candida krusei.
AB  - The antifungal susceptibility of 309 Candida glabrata and 63 Candida krusei
      clinical isolates was tested via the Sensititre YeastOne-3 system (Trek
      Diagnostic Systems, East Grinstead, UK) to compare the in vitro activity of
      voriconazole with that of five other antifungal agents (amphotericin B,
      fluconazole, itraconazole, ketoconazole, and flucytosine). Voriconazole was
      highly active (MIC90, 0.5 microg/ml) against isolates of both species, including
      those for which the MICs of itraconazole and fluconazole were high (MIC90s of
      itraconazole, 2 microg/ml for C. glabrata and 0.5 microg/ml for C. krusei; MIC90s
      of fluconazole, 32 microg/ml for C. glabrata and 64 microg/ml for C. krusei).
      Ketoconazole MIC90 values for both species were identical to those of
      voriconazole. The MIC90 of amphotericin B was similar for both species (0.125
      microg/ml for C. glabrata and 0.25 microg/ml for C. krusei). As expected,
      flucytosine was only moderately active against C. krusei isolates (MIC90, 16
      microg/ml) but was highly active against C. glabrata isolates (MIC90, 0.03
      microg/ml). Potential cross-resistance within the azole class was noted for some
      strains of C. glabrata (5.5%) that presented high MIC values for all the azoles
      tested. In order to consider voriconazole a viable alternative to other triazoles
      for the treatment of infections caused by Candida species, susceptibility testing
      of all clinically significant isolates of C. glabrata and C. krusei is
      recommended because of the potential for azole cross-resistance. The Sensititre
      YeastOne-3 seems to be a suitable commercial tool for this purpose.

PMID- 15258833
TI  - A 1-Mb critical region in six patients with 9q34.3 terminal deletion syndrome.
AB  - Patients with 9q34.3 terminal deletion usually show a clinically recognizable
      phenotype characterized by specific facial features (microcephaly, flat face,
      arched eyebrows, hypertelorism, short nose, anteverted nostrils, carp mouth and
      protruding tongue) in combination with severe mental retardation, hypotonia, and
      other anomalies. We analyzed six unrelated patients with a various 9q34.3
      terminal deletion. While having different-sized 9q34.3 deletions, all of these
      patients shared several distinctive anomalies. These anomalies are likely to
      arise from a commonly deleted region at distal 9q34.3. Fluorescence in situ
      hybridization (FISH) analysis using a dozen BAC clones mapped at the 9q34.13
      q34.3 region defined the shortest region of deletion overlap (SRO) as a 1-Mb
      segment proximal to 9qter containing eight known genes. Possible candidate genes
      delineating specific phenotypes of the 9q34.3 terminal deletion syndrome are
      discussed.

PMID- 15258832
TI  - Laboratory detection of group B Streptococcus for prevention of perinatal
      disease.
AB  - Group B Streptococcus (GBS) or Streptococcus agalactiae emerged in the 1970s as
      the leading cause of neonatal morbidity and mortality. Today, GBS remains one of
      the leading causes of sepsis and meningitis in newborns despite important
      prevention efforts, including the issuance of recommendations for prevention of
      perinatal GBS disease by the American College of Obstetricians and Gynecologists,
      the Centers for Disease Control and Prevention, and the American Academy of
      Pediatrics in 1996/1997. The gastrointestinal tract is the natural human
      reservoir for GBS and is the likely source of vaginal colonization. GBS disease
      in newborns usually results from ascending spread of GBS into the amniotic fluid,
      which leads to neonatal colonization and to invasive disease in some infants.
      This review analyzes the various laboratory methods available for the detection
      of GBS from clinical samples collected from pregnant women and will discuss their
      impact in the prevention of neonatal GBS infections and in the rationalization of
      antibiotic use. The recent commercial availability of a rapid and highly
      sensitive real-time polymerase chain reaction assay suitable for the specific
      detection of GBS from vagino-rectal samples obtained from pregnant women during
      delivery, which is approved by the US Food and Drug Administration, provides
      improvements in the accuracy and rapidity of GBS colonization screening compared
      to the standard culture-based method using the recommended selective enrichment
      broth.

PMID- 15258834
TI  - An association analysis between ApoA1 polymorphisms and the high-density
      lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese.
AB  - Association studies were performed to confirm the effect of polymorphisms in
      apolipoprotein A1 ( ApoA1) on the high-density lipoprotein cholesterol (HDL-C)
      level and the incidence of myocardial infarction (MI). A sequence analysis
      identified nine polymorphisms in ApoA1. After considering linkage disequilibrium,
      four polymorphisms in ApoA1 and four polymorphisms in the 5'-flanking regions and
      3'-flanking regions from the JSNP database were determined in 1,880 subjects
      recruited from the Suita study, which represents the general population in Japan.
      Of the eight polymorphisms tested, the ApoA1 T84C polymorphism had the greatest
      effect on the levels of HDL-C ( P=0.0005, P(c)=0.0040 corrected by the Bonferroni
      method) and triglyceride ( P<0.0001, P(c)=0.0008). The ApoA1 MspI polymorphism
      was not associated with HDL-C or triglyceride levels. We confirmed that the ApoA1
      T84C polymorphism was associated with the HDL-C level but not the triglyceride
      level in patients with MI ( n=637). Moreover, this polymorphism was associated
      with the incidence of MI in male subjects ( P=0.0326). A logistic analysis
      indicated that the frequency of MI in the CC genotype was lower than that in the
      CT+TT genotype ( P=0.0145, OR=0.4955, 95% CI: 0.2746-0.8525). The ApoA1 T84C
      polymorphism is an important marker for the HDL-C level and may be a new risk
      marker for MI in Japanese.

PMID- 15258835
TI  - Tetraether-linked membrane monolayers in Ferroplasma spp: a key to survival in
      acid.
AB  - Ferroplasma acidarmanus thrives in hot, extremely low pH, metal-rich solutions
      associated with dissolving metal sulfide ore deposits. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and thin layer
      chromatography analyses of F. acidarmanus membranes indicate that tetraether
      lipids predominate, with at least three core lipid structures. NMR measurements
      indicate that the cytoplasmic pH of F. acidarmanus is approximately 5.6. The
      optimal growth pH is approximately 1.2, and the lowest growth pH is approximately
      0.0. Thus, these organisms maintain pH gradients across their membranes that
      approach 5 pH units. Tetraether lipids were originally thought to be specifically
      associated with thermophiles but are now known to be widely distributed within
      the archaeal domain. Our data, in combination with recently published results for
      thermophilic and mesothermophilic acidophilic archaea, indicate that there may be
      a stronger association between tetraether lipids and tolerance to acid and/or
      large metal ion gradients.

PMID- 15258836
TI  - Spinal fusion in children with spina bifida: influence on ambulation level and
      functional abilities.
AB  - The aim of this study was to determine the influence of spinal fusion on
      ambulation and functional abilities in children with spina bifida for whom early
      mobilization was stimulated. Ten children (three males and seven females) with
      myelomeningocele were prospectively followed. Their mean age at operation was 9.3
      years (standard deviation (SD): 2.4). Spinal curvature was measured according to
      Cobb. Pelvic obliquity and trunk decompensation were measured as well. The
      ambulation level was scored according to Hoffer, and functional abilities, as
      well as the amount of caregiver assistance, were documented using the Pediatric
      Evaluation of Disability Inventory. All patients were assessed before surgery and
      three times after surgery, with a total follow-up duration of 18 months after
      surgery. After spinal fusion, magnitude of primary curvature decreased
      significantly (p=0.002). Pelvic obliquity and trunk decompensation did not
      change. In spite of less immobilization as compared with other reported
      experiences, ambulation became difficult in three out of four patients who had
      been able to ambulate prior to surgery. Functional abilities and amount of
      caregiver assistance concerning self-care (especially regarding dressing upper
      and lower body, and self-catheterization) and mobility (especially regarding
      transfers) showed a nonsignificant trend to deterioration within the first 6
      months after surgery, but recovered afterwards. From pre-surgery to 18 months
      after surgery, functional skills on self-care showed borderline improvement
      (p=0.07), whereas mobility did not (p=0.2). Mean scores on caregiver assistance
      improved significantly on self-care (p=0.03), and borderline on mobility
      (p=0.06), meaning that less caregiver assistance was needed compared with pre
      surgery. The complication rate was high (80%). In conclusion, within the first 6
      months after spinal fusion, more caregiver assistance is needed in self-care and
      mobility. It takes about 12 months to recover to pre-surgery level, while small
      improvement is seen afterwards. After spinal fusion, ambulation often becomes
      difficult, especially in exercise walkers. These findings are important for
      health-care professionals, in order to inform and prepare the patients and their
      parents properly for a planned spinal fusion.

PMID- 15258837
TI  - Therapeutic options and results following fixed atlantoaxial rotatory
      dislocations.
AB  - Atlantoaxial rotatory dislocation (AARD) represents a rare pathological condition
      of the upper cervical spine that is frequently misdiagnosed, leading to a delay
      in therapy. In a long-term assessment of clinical and radiological results, three
      different therapeutic options with regard to the length of the dislocation
      therapy interval (DTI) were evaluated. Twenty-six patients were treated for AARD
      from December 1988 until April 2000. Proper diagnosis was established after an
      average interval of 15 months. Three different therapeutical protocols were
      followed in order to reduce the dislocation: (1) closed transoral reposition
      under general anesthesia; (2) temporary transoral fixation utilizing the Harms T
      plate; (3) definitive transoral fusion. The eight patients treated by closed
      reduction had the best pain relief. The average visual analogue scale (VAS) score
      was 96.6 points, while the rotatory motion of the upper cervical spine, as
      assessed by dynamic MRI, was 25.3 degrees to each side. The length of the
      dislocation-therapy-interval (DTI) averaged 1.4 months. A mean VAS Score of 92.3
      points was recorded in the ten patients treated with a temporary fixation of
      C1/C2. In this subgroup the DTI had an average length of 5.3 months. The mean
      rotation to each side was 13.9 degrees . In the eight patients who underwent
      definitive fusion the mean VAS score was 60.6 points, while the average length of
      the DTI was 40.5 months. In conclusion, the clinical outcome and the subjective
      well-being following AARD deteriorates with increasing length of the dislocation
      therapy interval.

PMID- 15258838
TI  - Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies.
AB  - Peripheral neuropathy is a major dose-limiting side effect of many
      chemotherapeutic agents. The type and degree of neuropathy depend on the
      chemotherapy drug, dose-intensity, and cumulative dose. Disabling peripheral
      neuropathy has a significant negative impact on quality of life. Accordingly, a
      reliable assessment of chemotherapy-induced peripheral neurotoxicity is
      necessary, especially if potential neuroprotective agents are to be investigated.
      Chemoprotectants are agents that have been developed to ameliorate the toxicity
      associated with cytotoxic drugs. They aim to provide site-specific protection for
      normal tissues, without compromising antitumor efficacy. Several chemoprotectant
      compounds have been studied in recent clinical trials. These trials must include
      sufficient dose-limiting events for study and assessment of both toxicity and
      antitumor effect. A future avenue of investigation includes the identification of
      patients at higher risk for the development of peripheral neuropathy based on
      their genotype. Identification of these higher-risk patients may enable us to
      devise prevention strategies prior to the onset of this potentially debilitating
      complication.

PMID- 15258839
TI  - Communication training for health professionals who care for patients with
      cancer: a systematic review of effectiveness.
AB  - BACKGROUND: Effective communication is increasingly recognised as a core clinical
      skill. However, there is evidence that health and social care professionals still
      lack basic communication skills. PURPOSE: To assess the effectiveness of
      different communication skills training courses for health professionals in
      cancer care. METHODS: We searched six computerised databases and augmented this
      with a follow-up of references and grey (unpublished) literature. We included all
      studies evaluating communication training and assessed methodological quality
      according to the standard grading system of the Clinical Outcomes Group. Data on
      author, year, setting, objectives, study design and results were extracted and
      compared in tabular format. RESULTS: A total of 47 studies potentially assessing
      communication training in the area of cancer care were identified. Sixteen papers
      were included describing 13 interventions. Four were randomised controlled trials
      (RCTs) (grade I), with samples ranging from 72 to 233 subjects. The others were
      all grade III. Eleven interventions trained health professionals, two trained
      medical students. The outcomes measured included communication skills as assessed
      on audio or video, professionals' self-report and patient assessment. All the
      interventions demonstrated modest improvements (effect sizes ranged 0.15-2) and
      one found deterioration in the outcomes measured. CONCLUSION: Communication
      training improves basic communication skills. Positive attitudes and beliefs are
      needed to maintain skills over time in clinical practice and to effectively
      handle emotional situations.

PMID- 15258840
TI  - Alternaria spores in the atmosphere of Sydney, Australia, and relationships with
      meteorological factors.
AB  - Alternaria spores are found in the atmosphere in many locations around the world.
      They are significant from a human health perspective because they have been known
      to trigger allergic respiratory disease such as asthma and hay-fever. The
      presence of Alternaria spores in the atmosphere has been related to
      meteorological factors in past studies, but this has not been done previously in
      Sydney, Australia. This paper reports the results of such a study in Sydney.
      Alternaria spore concentration data for the period 19 August 1992 to 31 December
      1995 were examined with meteorological data for the same period. The daily
      Alternaria spore concentration was compared to the meteorological data for the
      same day and for up to 3 days previously. The analysis methods were Spearman's
      rank correlation and multiple regression. Alternaria spores appear in the
      atmosphere of Sydney year-round, although they peak over spring, summer, and
      autumn. A number of meteorological factors, including mean, minimum, and maximum,
      temperature, dew point temperature, and air pressure, are significantly
      correlated with the atmospheric concentration of Alternaria spores. Some of these
      meteorological variables (temperature and dew point temperature) show significant
      correlations with a 1, 2, and 3 day lag, as well as for the same day. Regression
      models indicate that up to 31.1% of the variation in Alternaria spore
      concentration can be explained by meteorological factors. There is potential for
      the results of this study to be used by public health authorities in the
      prediction of Alternaria spore concentrations in Sydney.

PMID- 15258841
TI  - [What is needed to develop a headache? Anatomical and pathophysiological
      implications].
AB  - The shared anatomical and physiological substrate for headache syndromes is the
      neural innervation of the cranial circulation. Evidence suggests, that the
      observed dilatation of vessels in trigeminal pain is not inherent to a specific
      headache syndrome but rather a feature of the physiology of the trigeminal neural
      innervation of the cranial circulation. Moreover, the impact of vascular changes
      for the generation of headaches remains elusive. The trigeminal nerve innervates
      blood vessels within ipsilateral meninges. Upon activation neuropeptides such as
      CGRP are released. Blockade of both the trigeminal nerve system and neuropeptides
      are crucial targets for headache alleviating drugs. While these mechanisms are
      well known the events within and outside the CNS which initiate headaches are
      poorly understood. This article will review the anatomy and physiology of the
      trigeminovascular system which demand renewed consideration of the neural
      influences in many primary headaches.

PMID- 15258842
TI  - Relationship between acute pyelonephritis, renal scarring, and vesicoureteral
      reflux. Results of a coordinated research project.
AB  - Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can
      subsequently lead to diverse complications. We prospectively evaluated 147
      females and 122 males (mean age 3.5 years) with APN in order to analyze the
      relationship between the presence of PRD, at the time of cortical renal
      scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and
      presence of vesicoureteral reflux (VUR). There were 152 children studied after
      the first proven UTI. VUR was present in 150 children. PRD was observed in 170
      children. There were no significant differences between boys and girls. PRD was
      found in 36.4% of children younger than 1 year and in 70.1% of those older than 1
      year ( P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children
      without VUR ( P<0.0001). Of children with a first episode of UTI, 55.9% developed
      PRD as did 72.6% of those with recurrent UTI ( P=0.004). Our results showed that
      PRD in children with APN is important, especially in the presence of VUR,
      recurrent UTI, and older age.

PMID- 15258843
TI  - Influence of diet on atherogenic risk in children with renal transplants.
AB  - Cardiovascular disease is one of the main causes of morbidity and mortality in
      recipients of renal transplants. Although the risk for cardiovascular disease is
      in part genetically determined, it may also be influenced by diet. The aim of the
      present study was to analyze the cross-sectional association of dietary intake of
      nutrients with biochemical markers of atherogenic risk. The influence of diet on
      the plasma profile of fatty acids was specifically investigated. Twenty-nine
      children and adolescents (mean age 14 years, range 6-18 years) with stable renal
      transplants and on a normal diet recorded their food intake for a period of 3
      days. The mean calorie intake was 40.6 kcal/kg per day (protein provided 16% of
      total calories, carbohydrates 45%, and fat 39%). Plasma levels of total
      cholesterol and low-density lipoprotein-cholesterol were significantly and
      positively related to intake of monounsaturated fatty acids ( r=0.66, P =0.007
      and r =0.62, P =0.02, respectively) and to plasma levels of elaidic acid, a trans
      fatty acid ( r=0.43, P =0.02 and r =0.54, P =0.01, respectively). Insulin
      resistance, estimated from values of plasma glucose ( r=0.70, P =0.03), plasma
      insulin ( r=0.59, P =0.02), and HOMA index ( r=0.62, P =0.01), was also directly
      related to the intake of monounsaturated fatty acids. Plasma plasminogen
      activator inhibitor-1 activity correlated positively with total fat intake (
      r=0.59, P =0.04). Plasma levels of homocysteine were negatively related to the
      intake of carbohydrates ( r=-0.62, P =0.02). We conclude that reasonable dietary
      recommendations to minimize the atherogenic risk in children with stable renal
      transplants should include a protein intake adjusted to the requirements for age,
      a large intake of carbohydrates leading to a low glycemic load, and a fat intake
      of less than 30% of the total calorie intake. The amount of monounsaturated and
      trans fatty acids in the diet should be especially limited. A sufficient intake
      of polyunsaturated fatty acids, with an adequate ratio between omega 6 and omega
      3 components, should also be provided.

PMID- 15258844
TI  - Cystatin C is a suitable marker of glomerular function in children with cancer.
AB  - Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on
      nephrotoxicity in childhood cancer are scanty, in part because of the
      difficulties in obtaining reliable markers of glomerular function. We used serum
      cystatin C (cysC) to assess glomerular function. CysC was compared with serum
      creatinine concentration (S(Cr)), the endogenous creatinine clearence ( C(Cr)),
      and the calculated Counahan formula ( C(Counahan)) in children with leukemia and
      solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay.
      Serum and urinary creatinine concentrations were determined by the Jaffe method.
      Samples were obtained from 258 children, including 92 receiving anticancer
      chemotherapy, 108 long-term survivors, 40 children without any renal disease, and
      18 patients with chronic renal insufficiency. CysC of patients on current
      chemotherapy was assessed both before and after treatment. Significant
      correlations were found between cysC and S(Cr) and between 1/cysC and C(
      Counahan). CysC increased significantly after cisplatin, methotrexate,
      cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest
      that cysC measurement can be used to characterize glomerular function in children
      with cancer.

PMID- 15258845
TI  - Natural history of multicystic kidney conservatively managed: a prospective
      study.
AB  - We report the long-term clinical results of conservative management of children
      with unilateral multicystic dysplastic kidneys (MCDK). Between 1989 and 2002, 43
      children with MCDK detected by prenatal ultrasonography were prospectively
      followed. At birth, ultrasonography confirmed the prenatal findings in all cases.
      Patients underwent a radioisotope scan and micturating cystogram in order to
      confirm the diagnosis and to exclude other uropathies. Follow-up ultrasound (US)
      examinations were performed at 6-month intervals during the first 2 years of life
      and yearly thereafter. The mean follow-up time was 42 months (range 12-156
      months). Two children developed hypertension during follow-up. In total 257 US
      scans were performed. The mean number of US scans per patient was 6 (range 3-10).
      US scans demonstrated partial involution of the MCDK in 30 (70%) cases and
      complete involution in 8 (19%). The absolute MCDK length remained almost
      unchanged in 5 children (11%). The estimated median time of complete involution
      of the MCDK was 122 months [95% confidence interval (CI)=86-158 months]. A total
      of 33 (76.7%) contralateral kidneys underwent compensatory hypertrophy, reaching
      a renal length above the 95th percentile during follow-up. The estimated median
      time for the occurrence of compensatory hypertrophy was 30 months (95% CI=15-45
      months). In conclusion, the natural history of MCDK is usually benign but
      patients must have long-term follow-up with US scans and blood pressure
      measurements.

PMID- 15258847
TI  - Reversible end-stage renal disease in an adolescent patient with methylmalonic
      aciduria.

PMID- 15258846
TI  - Measurement of renal functional reserve in children.
AB  - Renal functional reserve was measured during 89 studies in 78 children as the
      difference between the baseline glomerular filtration rate (GFR) and that
      following a protein meal. GFR was measured using creatinine as the filtration
      marker in children pre-treated with cimetidine. The children had been on a diet
      free of meat, fish, and fowl for 24 h. The protein meal to stimulate GFR was
      derived from milk, cheese, eggs, and baked goods. The increase in GFR following
      the protein meal was due mainly to an increase in the glomerular filtration of
      creatinine, with a small contribution by decreased serum creatinine
      concentration. This study confirmed that renal functional reserve can be measured
      using a meat-free protein meal to stimulate GFR. The protocol employed is a
      relatively noninvasive and inexpensive procedure for identifying glomerular
      hyperfiltration in children.

PMID- 15258848
TI  - Seed-caching responses to substrate and rock cover by two Peromyscus species:
      implications for pinyon pine establishment.
AB  - We examined whether pinyon mice ( Peromyscus truei) and brush mice ( P. boylii)
      could act as directed dispersal agents of pinyon pine ( Pinus edulis) through
      differential responses to soil particle size and rock cover. In field
      experiments, we allowed mice to either cache pinyon seeds or recover artificially
      cached seeds (pilfer) from quadrats containing large- or small-particle soils.
      Both species placed most (70%) seed caches in small-particle soil. Pilfering was
      the same from both particle sizes in the first year, while more seeds were
      pilfered from large-particle soils in the second year. In separate experiments,
      rock cover interacted with soil particle size, with both species placing over 50%
      of their caches in small-particle soil with rock cover. Overall, we found greater
      seed-caching in small-particle soils near rocks, with equal or lower pilfering
      from small-particle soils, suggesting more seeds would survive in small-particle
      soils near rock cover. Three lines of evidence supported the hypothesis that mice
      could act as directed dispersers by moving pinyon seeds to beneficial microsites
      for germination and establishment. First, in greenhouse experiments, pinyon seed
      germination was 4 times greater in small-particle soil cores than in large
      particle soil cores. Second, soils near rocks had significantly higher water
      content than areas of open soil at the driest time of the year, a critical factor
      for seedling survival in the arid southwestern USA. Third, 75% of juvenile pinyon
      trees were growing in small-particle soils, and 45% were growing near rock
      nurses.

PMID- 15258849
TI  - Competitive interactions between parasitoid larvae and the evolution of
      gregarious development.
AB  - We report experiments using two closely related species of alysiine braconids
      directed at understanding how gregarious development evolved in one subfamily of
      parasitoid wasps. Theoretical models predict that once siblicide between
      parasitoid wasps has evolved, it can only be lost under stringent conditions,
      making the transition from solitary to gregarious development exiguous.
      Phylogenetic studies indicate, however, that gregariousness has independently
      arisen on numerous occasions. New theoretical models have demonstrated that if
      gregarious development involves reductions in larval mobility, rather than a lack
      of fighting ability (as in the older models), the evolution of gregariousness is
      much more likely. We tested the predictions of the older tolerance models
      (gregariousness based on non-fighting larval phenotypes) and the reduced mobility
      models (gregariousness based on non-searching larval phenotypes) by observing
      larval movement and the outcome of interspecific competition between Aphaereta
      genevensis (solitary) and A. pallipes (gregarious) under multiparasitism.
      Differences in larval mobility matched the prediction of the reduced mobility
      model of gregarious development, with the solitary A. genevensis having larvae
      that are much more mobile. The proportion of hosts producing the solitary species
      significantly declined after subsequent exposure to females of the gregarious
      species. This contradicts the prediction of the older models (fighting vs non
      fighting phenotypes), under which any competitive interactions between solitary
      and gregarious larvae will result in a highly asymmetrical outcome, as the
      solitary species should be competitively superior. The observed outcome of
      interspecific competition offers evidence, with respect to this subfamily, in
      favour of the new models (searching vs non-searching phenotypes).

PMID- 15258850
TI  - Neurotoxicant-induced animal models of Parkinson's disease: understanding the
      role of rotenone, maneb and paraquat in neurodegeneration.
AB  - The etiologic basis of Parkinson's disease (PD), the second most common age
      related neurodegenerative disorder, is unknown. Recent epidemiological and
      experimental studies indicate that exposure to environmental agents, including a
      number of agricultural chemicals, may contribute to the pathogenesis of this
      disorder. Animal models are important tools in experimental medical science for
      studying the pathogenesis and therapeutic intervention strategies of human
      diseases. Since many human disorders do not arise spontaneously in animals,
      characteristic functional changes have to be mimicked by neurotoxic agents.
      Recently, agricultural chemicals, when administrated systemically, have been
      shown to reproduce specific features of PD in rodents, thus opening new routes
      for the development of animal models for this disorder. In addition to a brief
      historical overview of the toxin-induced PD models, this study provides a
      detailed description of exiting models in which Parkinsonism is initiated via the
      exposure of animals to such agricultural chemicals as rotenone, paraquat, and
      maneb. Suggested neurotoxicity mechanisms of these chemicals are considered, and
      the major lessons learned from the analysis of pesticide-induced PD models are
      discussed.

PMID- 15258851
TI  - Physical mapping of a rice lesion mimic gene, Spl1 , to a 70-kb segment of rice
      chromosome 12.
AB  - The rice lesion mimic mutant spotted leaf 1 ( spl1) was first identified in the
      rice ( Oryza sativa) cultivar Asahi in 1965. This mutant displayed spontaneous
      disease-like lesions in the absence of any pathogen, and was found to confer
      resistance to multiple isolates of rice blast. We employed a map-based cloning
      strategy to localize the Spl1 gene. A total of ten cleaved amplified polymorphic
      sequence (CAPS) markers linked to the Spl1 gene were identified and mapped to an
      8.5-cM region on chromosome 12. A high-resolution genetic map was developed using
      these ten CAPS markers and a segregating population consisting of 3202
      individuals. A BAC contig containing four BAC clones was constructed, and Spl1
      was localized to a 423-kb region. Seven spl1 mutants were obtained from the IR64
      deletion mutant collection, and molecular analysis using these mutants delimited
      the Spl1 gene to a 70-kb interval, covered by two BAC clones. These results
      provide the basis for cloning this gene, which is involved in cell death and
      disease resistance in rice.

PMID- 15258852
TI  - Molecular genetics of the Alhambra (Drosophila AF10) complex locus of Drosophila.
AB  - The Alhambra (Alh) gene is the Drosophila homologue of the human AF10 gene. AF10
      has been identified as a fusion partner of MLL, a human homologue of the fly gene
      trithorax, in infant leukemias. The endogenous function of human AF10 is not
      known, but may be vital to its role in acute leukemia. This prompted us to
      analyse Alh function. We describe here the genetic organisation of the Alh locus
      in D. melanogaster. We show that an independent lethal complementation group
      encoding a muscle protein (Mlp84B) is located within an Alh intron. We have
      already shown that the leucine zipper (LZ) domain of ALH activates several
      Polycomb group-responsive elements. We further demonstrate that the LZ domain on
      its own bears the Alh vital function, since it is necessary and sufficient for
      rescue of Alh mutant lethality. Finally, we demonstrate that, in contrast to a
      previous report, Alh does not affect position-effect variegation.

PMID- 15258853
TI  - Antifilarial activity of Zoanthus species (Phylum Coelenterata, Class Anthzoa)
      against human lymphatic filaria, Brugia malayi.
AB  - The chloroform methanol (1:1) extract of an unidentified green zoanthus (Phylum
      Coelenterata, Class Anthozoa) showed promising in vitro adulticidal activity with
      a lethal concentration of 125 microg/ml on Brugia malayi. This extract brought
      about a 52.2% reduction in circulating microfilariae of B. malayi when
      administered to infected Mastomys coucha at 250 mg/kg, orally for 5 consecutive
      days. Further fractionation of the extract led to the recovery of four fractions,
      which were evaluated simultaneously in both in vitro and in vivo systems against
      B. malayi. The chloroform fraction at 250 mg/kg orally for 5 days exhibited the
      highest macrofilaricidal action (42.5%), closely followed by the insoluble n
      butanol fraction (34.3%), the soluble hexane fraction (32.4%), and the soluble n
      butanol fraction (20.4%). In addition, the hexane soluble fraction caused 44.3%
      sterilization of the surviving female parasites. Two compounds isolated were
      found devoid of antifilarial activity.

PMID- 15258854
TI  - [Chemotherapy of the hormone-refractory prostate cancer].
AB  - The scepticism dominating the chemotherapy of the hormone-refractory prostate
      cancer (HRPC) has been replaced by a wave of enthusiasm. Phase II studies with
      taxane-containing combination therapies could achieve high response rate in some
      cases, and HRPC can not longer be deemed resistant to chemotherapy. It remains to
      be seen whether the combinations offer a survival advantage. This will be tested
      in phase III studies. Palliative chemotherapy should be considered in patients
      with HRPC if the initial hormone therapy was effective for a short time only and
      after several hormone therapies have been completed. Since chemotherapy is not
      yet an established standard therapy of HRPC, patients should be, if possible,
      included in clinical studies.

PMID- 15258855
TI  - [Xanthinuria with xanthine lithiasis in a patient with Lesch-Nyhan syndrome under
      allopurinol therapy].
AB  - PURPOSE: It is the intention of this report to identify appropriate analytical
      tests which allow for the monitoring of allopurinol treatment of patients with
      Lesch-Nyhan syndrome and the prevention of uric acid or xanthine lithiasis.
      MATERIALS AND METHODS: A 12 year old boy with Lesch-Nyhan syndrome presented with
      signs of compulsive automutilation, motoric and mental retardation and cerebral
      palsy. Paraclinical patient showed hyperuricemia and significant hyperuricosuria.
      During administration of allopurinol (200 mg/d) he developed fever, an urinary
      tract infection and dilatation of pelviureteric junction which was suspected of
      being nephrolithiasis. During hospitalisation, the purine metabolism was
      intensively monitored. The allopurinol treatment was adjusted according to
      clinical and laboratory data. RESULTS: The renal scanning diagnostic showed the
      develepment of a functionally impaired left kidney. Later this kidney had no part
      in tubulo-secretorical function. It was necessary to remove surgical two renal
      stones. The composition of the stones was exclusively xanthine. Serum
      concentration and urinary excretion of xanthine and hypoxanthine were massively
      enlarged. The elimination of uric acid in urine was normal. But subsequently, the
      left kidney had to be removed despite intensive care. CONCLUSION: Lesch-Nyhan
      syndrome is a disorder caused by congenital absence of the enzyme
      hypoxanthineguanine phosphoribosyltransferase and an increase of the enzyme
      activity of adenine phosphoribosyltransferase. Treatment should be adjusted to
      patient's age and weight. An adapt treatment with allopurinol and optimal fluid
      intake reduce the risk of uric acid or xanthine lithiasis. Laboratory monitoring
      includes testings for serum concentration and urinary excretion of uric acid,
      xanthine and hypoxanthine. Sole a normal concentration of uric acid is not
      sufficient for therapy control. Assessment of the urine sediment by microscopy or
      infrared spectroscopy will enable early detection of uric acid or xanthine
      lithiasis.

PMID- 15258856
TI  - [Investigation of diabetic men with erectile dysfunction to determine coronary
      flow reserve (CFR) and cardiac risk under medication with sildenafil (Viagra)].
AB  - PURPOSE: Since Sildenafil (Viagra) has become available, there have been reports
      of death and cardiac risks associated with its use. As large doses of Sildenafil
      medication is often prescribed particularly in diabetic patients with erectile
      dysfunction (ED), our study was designed to evaluate the coronary flow reserve
      (CFR) and possible resulting cardiac risk specifically in diabetic men. MATERIALS
      AND METHODS: Because these men often suffer from clinically significant ischaemic
      heart problems without their knowledge and without symptoms, all of our patients
      were examined by treadmill ECG and CFR. RESULTS: In 44 men (35 - 74 years) with
      type I and II diabetes also suffering from ED objectified by FCDS measurement of
      the penile vessels, a surprisingly high rate of objective cardiac problems were
      found, which were then verified by coronary angiography. These patients are at
      risk for ischaemic problems during Sildenafil-assisted intercourse and were
      excluded from further study. Interestingly, only 3 of theses 11 men would have
      been detected by conventional examinations. Patients free of coronary stenosis
      who received 50 mg Sildenafil (20 patients) showed no cardiac problems during
      treadmill exercise and CFR measurement. CONCLUSIONS: Coronary flow reserve in
      diabetic men lies at the lower end of the normal range, but is not further
      decreased by Sildenafil. However, diabetics with ED frequently showed coronary
      artery stenosis that was not clinically symptomatic. Furthermore, conventional
      cardiological examinations often fail to detect these patients, although they are
      at ischaemic risk during medically assisted intercourse. Furthermore, although 5
      of 20 men who received Sildenafil had an increase in penile blood flow without
      sexual stimulation, only 7 of 20 were responders to Sildenafil after take home
      medication. Thus, Sildenafil medication is not a suitable test medication for
      organic erectile dysfunction.

PMID- 15258857
TI  - [The relationship between uretero-cloacal structure in birds and sigmoidorectal
      pouch surgery].
AB  - PURPOSE: The present study was planned to investigate morphological, functional
      and histological properties of the natural ureterocloacal for in birds as well as
      to provide an appropriate information which may contribute to rectosigmoidal
      pouch surgery and to decrease its complications. MATERIALS AND METHODS: Thirty
      chickens (Gallus domesticus, 26 broilers, 4 layers) with a mean weight of 1870 +/
      88 g were used for this study. Histological and morphological evaluation of the
      cloaca was performed. Urethral reflux was estimated using X-rays. RESULTS: We
      found that the cloaca had three parts from cranial to caudal: coprodeum, urodeum
      and proctodeum respectively. A coprourodeal fold (CUF) between the coprodeum and
      urodeum and a uroproctodeal fold between the urodeum and proctodeum were
      detected. Settling of the muscle clusters both in the ureter and urodeum near the
      opening area appeared to be a strong sphincter structure and the ureters are
      opened to a structure covered by a transitional epithelium, which is similar to
      bladder in humans (connecting two identical epithelia). According to X-rays
      following the administration of a radio-opaque substance, there was no ureteral
      reflux in any of them. CONCLUSIONS: The natural urointestinal structure in birds
      has a spontaneous ureterointestinal anti-reflux opening. The coprourodeal fold
      that prevents the mixing of faeces and urine, inhibits the effects of increased
      pressure and prevents the reflux of urine to the upper segments is provided with
      many of desired hinders properties for urointestinal diversion.

PMID- 15258858
TI  - [Ureteropelvic stenosis, agenesia of the contralateral kidney and sinistral
      inferior vena cava].
AB  - INTRODUCTION: Ureteropelvic stenosis occurs as a result of intraluminal or
      extraluminal alterations at the ureteropelvic junction. It is the most common
      cause of upper urinary tract obstruction. CASE REPORT: We report about a rare
      case of a man with ureteropelvic junction obstruction and a renal pelvic stone
      accompanied by other congenital anomalies, including a sinistral inferior vena
      cava and agenesis of the opposite kidney. Multiple vessels were present in front
      of the renal pelvis, while the renal vein itself was situated dorsal to the left
      renal pelvis, resulting in compression and obstruction of the ureteropelvic
      junction. Dismembered pyeloplasty using the Anderson-Hynes technique was
      performed placing the ureter dorsal to the renal vein. CONCLUSION: Various
      vascular anomalies, especially in the region of the vena cava, can result in
      renal vasculature abnormalities and development of secondary ureteropelvic
      stenosis. Ureteropelvic stenosis may coexist with other congenital defects.

PMID- 15258859
TI  - [Suprapubic adenomectomy].

PMID- 15258860
TI  - Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as
      the cause of Bardet-Biedl syndrome (BBS3).
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic human
      disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac
      malformations, learning disabilities, and hypogenitalism. Eight BBS loci have
      been mapped, and seven genes have been identified. BBS3 was previously mapped to
      chromosome 3 by linkage analysis in a large Israeli Bedouin kindred. The rarity
      of other families mapping to the BBS3 locus has made it difficult to narrow the
      disease interval sufficiently to identify the gene by positional cloning. We
      hypothesized that the genomes of model organisms that contained the orthologues
      to known BBS genes would also likely contain a BBS3 orthologue. Therefore,
      comparative genomic analysis was performed to prioritize BBS candidate genes for
      mutation screening. Known BBS proteins were compared with the translated genomes
      of model organisms to identify a subset of organisms in which these proteins were
      conserved. By including multiple organisms that have relatively small genome
      sizes in the analysis, the number of candidate genes was reduced, and a few genes
      mapping to the BBS3 interval emerged as the best candidates for this disorder.
      One of these genes, ADP-ribosylation factor-like 6 (ARL6), contains a homozygous
      stop mutation that segregates completely with the disease in the Bedouin kindred
      originally used to map the BBS3 locus, identifying this gene as the BBS3 gene.
      These data illustrate the power of comparative genomic analysis for the study of
      human disease and identifies a novel BBS gene.

PMID- 15258861
TI  - Accuracy of ED triage of psychiatric patients.
AB  - The study objective was to determine the accuracy of initial triage assessment
      (ITA) in directing behavioral emergency patients to appropriate medical or
      psychiatric care, and to identify variables that enhance triage accuracy. A
      cohort study of 436 adult patients with 1 of 10 behavioral-related complaints was
      conducted. ITA compared with the final ED diagnosis, both of which were
      classified as either "medical" or "psychiatric." Patient triage characteristics
      correlated with the final ED diagnosis using logistic regression. Sensitivity of
      ITA for predicting a medical final ED diagnosis was 70% (95% CI 60.1, 78.5) and
      specificity 85% (95% CI 80.6, 88.7). ITA agreed with final ED diagnosis in 344
      (81.3%) and these patients had a significantly shorter ED length of stay (4.50 v
      5.90 hours, p=0.03). Dementia, past psychiatric history, family history of
      psychiatric illness, and ITA were significant predictors of final ED diagnosis.
      ITA is a fair predictor of the final ED diagnosis, but could be enhanced by
      screening for dementia and past psychiatric history. Improved triage accuracy
      could reduce length of stay for such patients.

PMID- 15258862
TI  - Cosmetic outcomes of facial lacerations repaired with tissue-adhesive,
      absorbable, and nonabsorbable sutures.
AB  - The objective of this study was to compare the 9- to 12-month cosmetic outcome of
      facial lacerations closed with rapid-absorbing gut suture (RG),
      octylcyanoacrylate (OC), or nylon suture (NL). We hypothesized that no important
      differences would exist between these methods. This prospective, randomized study
      enrolled consecutive patients with facial lacerations when experienced physician
      assistants were on duty for wound closure. Patients returned at 9 to 12 months
      for cosmetic evaluation. Two blinded physicians performed visual analog cosmesis
      scale (VACS) scoring, and the patient completed a VAS satisfaction score. One
      hundred forty-five patients were enrolled. Nine-month follow up occurred in 84
      patients. The maximum difference within each evaluator's set of scores was 3.6
      mm, well below the minimum clinically important difference (MCID) of 10 to 15 mm.
      We did not detect clinically important differences in cosmetic outcome at 9 to 12
      months in patients with facial lacerations closed with RG, OC, or NL, although RG
      or OC could be preferred to eliminate follow-up visits for suture removal.

PMID- 15258863
TI  - The utility of screening laboratory studies in pediatric patients with sickle
      cell pain episodes.
AB  - The purpose of this study was to determine whether blood counts discriminate
      between sickle cell pain episodes that lead to successful discharge from the
      emergency department (ED) and those that result in complications. This
      retrospective review compared the hemoglobin, reticulocyte count, and white blood
      cell count with differential during complicated and uncomplicated ED visits.
      Complicated visits were pain episodes followed by admission, by readmission
      within 48 hours, by acute chest syndrome, by an aplastic crisis, or by the
      administration of blood or antibiotics. There were 2 statistically important
      differences between complicated and uncomplicated pain episodes. Children
      successfully discharged were younger than those experiencing a complicated visit
      (8.9 v 11.2, P = 0.04). At a difference of 0.4 g/dL, the change in hemoglobin
      from baseline among children with complicated versus uncomplicated pain crises
      was not clinically useful. Routinely performed blood counts do not reliably
      identify the course of sickle cell pain crises.

PMID- 15258864
TI  - Gas flow rates through transtracheal ventilation catheters.
AB  - The purpose of the study was to measure gas flow rates using different methods of
      transtracheal ventilation. Wall oxygen flow (WOF) at 10 and 15L/min, and a self
      inflating ventilation bag (SIVB) were used to deliver gas flow through three
      transtracheal catheters: 13, 14, and 16 gauge (5 trials each). WOF mean gas flow
      rates (L/min) through the 16G, 14G, 13G catheters, respectively were: 15.7, 15.7,
      16.8 at 15L/min, 10.5, 10.5, 10.3 at 10 L/min, and 5.7, 7.5, 7.7 via SIVB. SIVB
      gas flow was not continuous since it required the bag to reinflate, which reduces
      its calculated flow rate. A 500 cc tidal volume can be delivered within 3 seconds
      (WOF) and 5 seconds (SIVB). Catheter size did not substantially affect gas flow
      rates (Poiseuille's law not applicable). Transtracheal ventilation is best done
      by using WOF, but if a device to perform this is not available, then an SIVB may
      still be sufficient.

PMID- 15258865
TI  - Mass smallpox immunization program in a deployed military setting.
AB  - A prospective, observational study of immunizing over 6,000 active-duty troops
      against smallpox in a 4-week time period was conducted. It focused on the
      complications of the vaccine and lost workdays. Comparison is made to the
      complication rates of earlier smallpox immunization programs. In direct response
      to elevated bioterrorism concerns, the United States military and civilian first
      responders have begun a mass smallpox immunization program. This article reviews
      the experience with implementing such a program in a forward-deployed location
      while maintaining military readiness. The objectives were to assess the impact of
      a mass smallpox immunization program on operations in a forward-deployed military
      setting and to comment on lessons learned in the screening and immunization
      process. From January 16, 2003 through February 11, 2003 6,002 members of the
      United States military were immunized in a forward-deployed location. Information
      was obtained using data from the Air Force Complete Information Tracking
      Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan
      to calculate the following Main Outcome Measures data: (1)Percentage of
      individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC
      criteria, (3) Number of serious complications, (4) Number of life-threatening
      complications, and (5) Number of manpower days lost as a complication of the
      vaccine. A total of 6,739 individuals were screened for vaccination with 6,348
      (94%) remaining eligible for the vaccine. The "take" rate for the vaccine was
      98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The
      immunization program produced an additional 156 medical visits (2.6% of patients
      required one visit). A total of 0.55% of immunized individuals lost one or more
      work days. In conclusion, a mass smallpox vaccination program can be effectively
      administered in a forward-deployed military setting despite high tempo military
      operations with minimal operational impact.

PMID- 15258866
TI  - Ability of CT to alter decision making in elderly patients with acute abdominal
      pain.
AB  - The study objective was to assess the ability of computerized tomography (CT) to
      alter clinical decision-making in the evaluation of elderly Emergency Department
      (ED) patients with abdominal pain. A prospective, observational cohort study of a
      convenience sample of ED patients, 65 years of age, with abdominal or flank pain
      of 1-week duration was conducted. ED attending physicians completed a structured
      data collection instrument recording 5 primary endpoints before and after CT.
      Change in frequency of each of these 5 endpoints from pre- to post-CT comprised
      the target outcome variables. Of 104 eligible patients, CT altered the admission
      decision in 26% (95%CI 18, 34%)]; need for surgery in 12% (95% CI 6%, 18%); need
      for antibiotics in 21% (95% CI 13%, 29%) and suspected diagnosis in 45% (95% CI
      35%, 55%). The proportion of cases in which physicians reported a high degree of
      certainty in the suspected diagnosis increased from 36% pre-CT (95%CI 26,44%) to
      77% post-CT (95% CI 69, 85%). Diagnosis and disposition were altered by CT in
      about one-half and one-quarter of patients, respectively, concurrent with a
      doubling in diagnostic certainty. CT has the ability to significantly alter
      clinically important decisions in elderly patients with abdominal pain.

PMID- 15258867
TI  - Unpowered scooter injuries reported to the Consumer Product Safety Commission:
      1995-2001.
AB  - There has been a marked increase in the use of unpowered scooters over the past
      few years. Along with this, there has been an increase in injuries related to
      their use. The objective of this study was to review the unpowered scooter
      related injury reports compiled by the United States Consumer Product Safety
      Commission (CPSC) and to describe the scope and type of injuries sustained. A
      consecutive case series of injuries sustained by individuals using unpowered
      scooters between January 1995 and June 2001 was compiled by the CPSC and was made
      available for review. Data collected included general demographics, date and type
      of injury, a brief description of the event, treatment, and outcomes. Data are
      reported using descriptive statistics. During the study period, 469 unique cases
      of unpowered scooter-related injuries were compiled by the CPSC and reviewed for
      the present analysis. The median age of those injured was 10 years (range, 1-70
      y) with 63% male. Of those injured, 24 (5.1 %) required hospitalization. The most
      frequent injuries were lacerations (26%), fractures (22%), and contusions (16%).
      Of interest; 15 deaths were reported. A broad spectrum of injuries was reported
      to the CPSC related to the use of unpowered scooters. Although most injuries were
      relatively minor, there were 15 deaths reported. Although most injuries occurred
      in older children and young adolescents, the very young and adults were not
      immune from injuries. The risk of injury from unpowered scooters and the need for
      safety awareness should be stressed to all individuals including the very young
      and adults.

PMID- 15258868
TI  - ED presentation of neutropenic enterocolitis in adult patients with acute
      leukemia.
AB  - The purpose of this study was to investigate the initial clinical features and
      subsequent outcomes in patients with adult leukemia with typhlitis or neutropenic
      enterocolitis. A retrospective review of 10 episodes of neutropenic enterocolitis
      in nine patients (age range, 21-71 years) with acute leukemia from March 1, 1990,
      through February 28, 2002, was conducted. In clinical presentations, fever
      appears in all patients, followed by abdominal pain or tenderness (90%) and
      diarrhea (60%), respectively. In particular, three cases were coincidentally
      diagnosed as leukemia before any chemotherapy. The most common diagnostic
      modality used for the diagnosis of neutropenic enterocolitis was computed
      tomography (CT) scan (seven episodes). Medical treatments, including broad
      spectrum antibiotics, bowel rest, and total parenteral nutrition, were applied to
      seven patients. Laparotomy with bowel resection was performed on two patients
      with bowel necrosis and severe peritonitis. Of all nine cases, six were fatal as
      a result of sepsis, a common complication of neutropenic enterocolitis. As the
      incidence of neutropenic enterocolitis increases in patients with acute leukemia,
      EPs should be alert and make an early diagnosis of this rapidly deteriorated and
      life-threatening disease.

PMID- 15258869
TI  - Does morphine change the physical examination in patients with acute
      appendicitis?
AB  - The objective of this study was to determine if judicious dosing of morphine
      sulfate can provide pain relief without changing important physical examination
      findings in patients with acute appendicitis. We conducted a prospective,
      randomized, double-blind crossover design. Patients scheduled for appendectomy
      were randomized to two groups. Group A received 0.075 mg/kg intravenous morphine
      sulfate and 30 minutes later received placebo. The sequence of medication was
      reversed in group B. Patients were examined by a surgical resident and an EM
      attending before and after receiving medication. Six explicit physical
      examination findings were documented as absent, indeterminate, or present.
      Physicians were also asked if they felt overall examination findings had changed
      after medication. Patient's visual analog scale (VAS) was recorded before each
      medication and at study completion. Thirty-four patients were enrolled and full
      data were available for 22 patients. Neither morphine nor placebo caused a
      significant change in individual examination findings. Three patients in both
      groups were judged to have a change in their examination after medication. The
      median change in VAS was 20 mm after morphine and 0 mm after placebo (P =.01). In
      this pilot study, patients with clinical signs of appendicitis were treated with
      morphine and had significant improvement of their pain without changes in their
      physical examination.

PMID- 15258870
TI  - Patient expectations for pain relief in the ED.
AB  - The objective of the study was to assess patient expectations for pain relief in
      the ED. A convenience sample of 522 patients with pain and 144 patients without
      pain were enrolled in a prospective observational study at a university ED.
      Patients reported a mean expectation for pain relief of 72 % (95% CI 70-74).
      Eighteen percent expected complete (100%) pain relief in the ED. Patient
      expectations for pain relief were poorly correlated (r = 0.150) with initial pain
      intensity. Patients without pain reported a mean expectation for pain relief of
      74% (95% CI 71-77) if they had presented with pain. There were no differences in
      patient expectations for pain relief based on age or gender. Patients expect a
      large percentage of their pain to be relieved in the ED, and many expect complete
      analgesia. Patient expectations for pain relief do not vary based on age, gender
      or pain intensity.

PMID- 15258871
TI  - Tracheal rupture complicating emergent endotracheal intubation.
AB  - Tracheal rupture is rare in clinical practice. We present 2 female patients with
      tracheal rupture after emergent endotracheal intubation from different injury
      mechanisms; penetrating injury of using stylet during intubation in one case and
      overinflation of cuff of the endotracheal tube under rapid sequence intubation in
      another. The lesions of rupture could be detected by bronchoscopy and
      reconstructive 3-dimensional computed tomography. Both cases received surgical
      repair without complication. In our report, reconstructive 3-dimensional computed
      tomography scrupulously detected the rupture sites and provided the noninvasive
      modality for diagnosis. We review the literature of tracheal rupture after
      emergent endotracheal intubation in respects of the diagnosis, the possible
      mechanisms of the injury, and suggest strategies of management.

PMID- 15258872
TI  - Echocardiographic visualization of acute pulmonary embolus and thrombolysis in
      the ED.
AB  - Echocardiography has been used to diagnose acute right-sided dysfunction arising
      from pulmonary embolism (PE). Rarely, it can visualize the embolic material in
      the right heart cavities. We report a case of acute PE that was seen in the right
      ventricle and right pulmonary artery using bedside transthoracic echocardiography
      in the ED. As a result of the prompt diagnosis of a massive embolus and
      associated right ventricular dysfunction, the patient was treated with
      thrombolytics. Serial echocardiographs confirmed the response to therapy and the
      dissolution of thrombi. In this report, echocardiographic findings of acute PE
      and indications of thrombolytics in PE are also reviewed from the literature.
      Based on available evidence, those patients who present with cardiogenic shock
      from PE, and young patients with acute PE leading to right ventricular
      dysfunction benefit the most from early thrombolytic therapy.

PMID- 15258873
TI  - Combined computed tomography venography and pulmonary angiography for the
      diagnosis PE and DVT in the ED.
AB  - The purpose of this study is to evaluate the usefulness of combined computed
      tomography venography and pulmonary angiography (CTVPA) in the diagnosis of
      venous thromboembolic (VTE) disease in the emergency department (ED). CTVPA
      images and clinical data of 73 nonselected patients with suspected pulmonary
      embolism (PE) and/or deep venous thrombosis (DVT) were retrospectively assessed.
      CTVPA correctly identified 33 of 34 patients with VTE disease, including 7
      patients with PE alone, 11 patients with DVT alone, and 16 patients with both PE
      and DVT. Among the 27 patients with DVT, CTVPA disclosed thrombosis involving the
      abdominal and pelvic veins in 4 patients, and isolating to the inferior vena cava
      and iliac vein in one patient. CTVPA showed high accuracy in the diagnosis of
      both PE and DVT, in comparison with lower extremity venous sonography and
      ventilation-perfusion scintigraphy. In 26 (66%) of the 39 patients without of
      evidence VTE, CTVPA provided important ancillary information that suggests
      additional or alternative diagnoses. CTVPA is therefore an appropriate single
      diagnostic tool for evaluation VTE disease in the ED.

PMID- 15258874
TI  - Altered consciousness and lethargy from compromised intestinal blood flow in
      children.
AB  - Altered state of consciousness and lethargy could be early and cardinal
      complaints in diseases that actually originate within the abdomen. Thirteen
      children were seen at our departments in whom impairment of the individual's
      mental state preceded the appearance of common gastrointestinal symptoms. Whereas
      in infants with intussusception of childhood neurological signs and symptoms have
      been rarely mentioned, references to an altered state of consciousness and
      lethargy in volvulus, strangulation or bowel incarceration have not been
      previously reported. Recognition of this possibility, however, should be taken
      into account in the diagnostic work-up of children presenting with inexplicable
      alterations of their mental state.

PMID- 15258875
TI  - Procedural sedation use in the ED: management of pediatric ear and nose foreign
      bodies.
AB  - This is the first report of which we are aware that describes the use of
      procedural sedation for the emergency department management of ear and nose
      foreign bodies in children < 18 years of age. During a 5.5-year period, we
      identified 312 cases of children with a foreign body in a single orifice (174
      ear, 138 nose). Procedural sedation was performed in 23% of cases (43 ear, 28
      nose) and ketamine was used most commonly (92%). Emergency physicians had a high
      rate of success in removing foreign bodies (84% ear, 95% nose) and a low
      complication rate. Procedural sedation had a positive effect on the success rate
      as more than half of the sedation cases had undergone failed attempts without
      sedation by the same physician. Emergency physicians should have familiarity with
      this indication for procedural sedation.

PMID- 15258876
TI  - Bedside emergency ultrasonography in the evaluation of a perirectal abscess.

PMID- 15258877
TI  - Subdural hematoma after diagnostic lumbar puncture.

PMID- 15258878
TI  - Patterns of heroin overdose-induced pulmonary edema.

PMID- 15258879
TI  - The effectiveness of wireless telephone communication technology on ambient noise
      level reduction within the ED.

PMID- 15258880
TI  - Coronary embolus secondary to a prosthetic mitral valve and subtherapeutic
      anticoagulation.

PMID- 15258881
TI  - Podagra, is it always gout?

PMID- 15258882
TI  - Tension chylothorax caused by occult trauma.

PMID- 15258883
TI  - Changes in pediatric toxic dose of acetaminophen.

PMID- 15258884
TI  - Spontaneous reduction of a small bowel intussusception in a patient with Henoch
      Schonlein purpura.

PMID- 15258885
TI  - The emergent airway: what drugs and adjuncts do emergency physicians prefer?

PMID- 15258886
TI  - Ecstasy overdose: rapid cooling leads to successful outcome.

PMID- 15258887
TI  - Late administration of pralidoxime in organophosphate (fenitrothion) poisoning.

PMID- 15258888
TI  - Dichlorvos poisoning after intramuscular injection.

PMID- 15258889
TI  - No QT interval prolongation associated with quetiapine overdose.

PMID- 15258890
TI  - Acute human immunodeficiency virus infection presenting with erythema multiforme.

PMID- 15258891
TI  - Prediction of survival from cardiopulmonary resuscitation by CPR instructors.

PMID- 15258892
TI  - Corneal abrasion from Vick's Vapor.

PMID- 15258893
TI  - Endothelial cell barrier regulation by sphingosine 1-phosphate.
AB  - Disruption of vascular barrier integrity markedly increases permeability to fluid
      and solute and is the central pathophysiologic mechanism of many inflammatory
      disease processes, including sepsis and acute lung injury (ALI). Dynamic control
      of the endothelial barrier involves complex signaling to the endothelial
      cytoskeleton and to adhesion complexes between neighboring cells and between
      cells and the underlying matrix. Sphingosine 1-phosphate (S1P), a biologically
      active lipid generated by hydrolysis of membrane lipids in activated platelets,
      organizes actin into a strong cortical ring and strengthens both intercellular
      and cell-matrix adherence. The mechanisms by which S1P increases endothelial
      barrier integrity remain the focus of intense basic research. The downstream
      structural changes induced by S1P interact to decrease vascular permeability to
      fluid and solute, which translates into a reduction lung edema formation in
      animal models of ALI, thus suggesting a potentially life-saving therapeutic role
      for vascular barrier modulation in critically ill patients.

PMID- 15258894
TI  - Thrombogenic and atherogenic activities of lysophosphatidic acid.
AB  - Lysophosphatidic acid (LPA) has been identified as a biologically active lipid in
      mildly-oxidized LDL, human atherosclerotic lesions, and the supernatant of
      activated platelets. The evidence that LPA has thrombogenic and atherogenic
      activities has increased substantially in recent years. Supporting the
      thrombogenic activity of LPA, analysis of the core region of human carotid
      plaques revealed recently the presence of alkyl- and acyl-molecular species from
      LPA with high platelet-activating potency (16:0 alkyl-LPA, 20:4 acyl-LPA). LPA,
      lipid extracts of atherosclerotic plaques, and the lipid-rich core elicited shape
      change and, in synergy with other platelet stimuli, aggregation of isolated
      platelets. This effect was completely abrogated by prior incubation of platelets
      with LPA receptor antagonists. Furthermore, LPA at concentrations approaching
      those found in vivo, induced platelet shape change, aggregation, and platelet
      monocyte aggregate formation in blood. LPA-stimulated platelet aggregation was
      mediated by the ADP-stimulated activation of the P2Y(1) and P2Y(12) receptors.
      Supporting its atherogenic activity, LPA is a mitogen and motogen to vascular
      smooth muscle cells (VSMCs) and an activator of endothelial cells and
      macrophages. Recently, LPA has been identified as an agonist of the peroxisome
      proliferator activating receptor gamma (PPARgamma), which is a key regulator of
      atherogenesis. LPA elicits progressive neointima formation, which is fully
      abolished by GW9662, an antagonist of PPARgamma. We propose that LPA plays a
      central role in eliciting vascular remodeling and atherogenesis. Furthermore,
      upon rupture of lipid-rich atherosclerotic plaques, LPA may trigger platelet
      aggregation and intra-arterial thrombus formation. Antagonists of LPA receptors
      might be useful in preventing LPA-elicited thrombus formation and neointima
      formation in patients with cardiovascular diseases.

PMID- 15258895
TI  - Mechanisms of cardioprotection by lysophospholipids.
AB  - The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphosphatidic acid
      (LPA) reduce mortality in hypoxic cardiac myocytes. S1P is also cardioprotective
      in both mouse and rat models of cardiac ischemia/reperfusion (I/R) injury.
      Although these results are consistent with prior work in other cell types, it is
      not known what signaling events are critical to cardioprotection, particularly
      with respect to ceramide and the preservation of mitochondrial function, which is
      essential for cardiac cell survival. Neither receptor regulation nor signaling
      has been studied during I/R in the heart with or without the application of S1P
      or LPA. The role of sphingosine kinase in I/R and in ischemic preconditioning
      (IPC) has not been defined, nor has the fate or function of S1P generated by this
      enzyme, particularly during preconditioning or I/R, been elucidated. Whether S1P
      infused systemically in animal models of myocardial infarction in which survival
      is an end-point will be hemodynamically tolerated has not been determined. If
      not, the substitution of agents such as the monosialoganglioside GM-1, which
      activates sphingosine kinase, or the development of alternative ligands for S1P
      receptors will be necessary.

PMID- 15258896
TI  - Sphingosine 1-phosphate and its G protein-coupled receptors constitute a
      multifunctional immunoregulatory system.
AB  - The lysophospholipid growth factors sphingosine 1-phosphate (S1P) and
      lysophosphatidic acid (LPA) are generated by many cells involved in immunity,
      including macrophages, dendritic cells, mast cells, and platelets, with resultant
      lymph and plasma concentrations of 0.1-1 microM. All immune cells express
      distinctive profiles of G protein-coupled receptors (GPCRs) for S1P and LPA,
      which are regulated developmentally and by cellular activation. For T-cells,
      constitutive S1P signaling through their principal S1P(1) GPCR inhibits
      chemotactic responses to chemokines, with lesser suppression of proliferation and
      cytokine production. These S1P-S1P(1) GPCR signals tonically reduce T-cell
      chemotactic sensitivity to chemokines and thereby limit homing of blood and
      spleen T-cells to secondary lymphoid tissues. S1P(1) GPCR antagonists evoke
      lymphopenia by permitting blood T-cells to enter lymph nodes and blocking S1P(1)
      GPCR-dependent T-cell efflux from lymph nodes. Inversely, there is a longer than
      normal persistance in blood and a decrease in lymphoid transit time for T-cells
      overexpressing transgenic S1P(1) GPCRs. The immunotherapeutic potential of S1P(1)
      GPCR antagonists derives from their capacity to limit T-cell access to organ
      grafts and autoimmune antigens without reducing their other intrinsic functional
      capabilities. Lysophospholipids and their GPCRs thus constitute an
      immunoregulatory system of sufficient prominence for pharmacological targeting in
      transplantation, autoimmunity and immunodeficiency.

PMID- 15258897
TI  - Lysophosphatidic acid production and action: validated targets in cancer?
AB  - The completion of the human genome project, the evolution of transcriptional
      profiling and the emergence of proteomics have focused attention on these areas
      in the pathophysiology and therapy of cancer. The role of lysophospholipids as
      potential mediators in cancer pathophysiology, screening and management has taken
      a major leap forward with the recent cloning of several enzymes involved in the
      metabolism of lysophospholipids. Lysophospholipids, although small molecules,
      contain a high "informational" content. Differences include the nature of the
      phosphate head group, the regiochemistry of the fatty acyl chain on the glyceryl
      backbone, the presence of ether versus ester linkages to the backbone, and the
      length and saturation of the fatty acyl or alkyl chain. This informational
      content is sufficient to result in a marked structure function activity
      relationship at their cognate receptors. Thus the emerging discipline of
      "functional lipidomics" is likely to prove as important as genomics and
      proteomics in terms of early diagnosis, prognosis, and therapy. Lysophospholipid
      levels are elevated in vivo in a number of pathophysiological states including
      ascitic fluid from ovarian cancer patients indicating a role in the
      pathophysiology of this devastating disease. Although controversial, levels of
      specific lysophospholipids may be altered in the blood of cancer patients
      providing a potential mechanism for early diagnosis. Several of the enzymes
      involved in the metabolism of lysophospholipids are aberrant in ovarian and other
      cancers. Further, the enzymes are active in the interstitial space, rendering
      them readily accessible to the effects of inhibitors including antibodies,
      proteins, and small molecules. In support of a role for lysophospholipids in the
      pathophysiology of cancer, expression of receptors for lysophospholipids is also
      aberrant in cancer cells from multiple different lineages. All of the cell
      surface receptors for lysophospholipids belong to the G protein coupled receptor
      family. As over 40% of all drugs in current use target this family of receptors,
      lysophospholipid receptors are highly "druggable." Indeed, a number of highly
      specific agonists and antagonists of lysophospholipid receptors have been
      identified. A number are in preclinical evaluation as therapeutics. We look
      forward to the next several years when the role of lysophospholipids in
      physiology and the pathophysiology and management of cancer and other diseases
      are fully elucidated.

PMID- 15258898
TI  - Inhibition of phenylephrine-induced cardiac hypertrophy by docosahexaenoic acid.
AB  - Many of the cardiovascular benefits of fish oil result from the antiarrhythmic
      actions of the n-3 polyunsaturated lipids docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA). The beneficial effects of DHA/EPA in patients with
      coronary artery disease and myocardial infarction may also result from modulation
      of the myocardial hypertrophic response. Hypertrophy was assessed in neonatal
      cardiomyocytes exposed to phenylephrine (PE) by measuring cell surface area,
      total protein synthesis ((14)C leucine incorporation), and the organization of
      sarcomeric alpha-actinin and by monitoring expression of atrial natriuretic
      factor (ANF). We report that PE induced a twofold increase in cell surface area
      and protein synthesis in cardiomyocytes. The hypertrophied cardiomyocytes also
      exhibited increased expression of ANF in perinuclear regions and organization of
      sarcomeric alpha-actinin into classical z-bands. Treatment of cardiomyocytes with
      5 microM DHA effectively prevented PE-induced hypertrophy as shown by inhibition
      of surface area expansion and protein synthesis, inhibition of ANF expression,
      and prevention of alpha-actinin organization into z-bands. DHA treatment
      prevented PE-induced activation of Ras and Raf-1 kinase. The upstream inhibition
      of Ras --> Raf-1 effectively prevented translocation and nuclear localization of
      phosphorylated extracellularly regulated kinase 1 and 2 (Erk1/2). These effects
      consequently led to inhibition of nuclear translocation, and hence, activation of
      the downstream signaling enzyme p90 ribosomal S6 kinase (p90(rsk)). These results
      indicate that PE-induced cardiac hypertrophy can be minimized by DHA. Our results
      suggest that inhibition of Ras --> Raf-1 --> Erk1/2 --> p90(rsk) --> hypertrophy
      is one possible pathway by which DHA can inhibit cardiac hypertrophy. In vivo
      studies are needed to confirm these in vitro effects of DHA.

PMID- 15258899
TI  - Increased density of retinal pigment epithelium in cd81-/- mice.
AB  - Our laboratories have focused on the role of the tetraspanin CD81 in the
      regulation of mitotic activity. Previously we have shown that antibodies directed
      against CD81 can block the proliferation of cultured retinal pigment epithelial
      (RPE) cells. The present study investigates the role of this protein by analyzing
      the structure of the adult retina in mice with a null mutation of cd81. Adult
      cd81(-/-) mice were produced by crossing two inbred strains, NIHS-BC/Tac and
      129X1/SvJ, carrying the cd81 mutation as heterozygotes (+/-). Seven cd81(-/-)
      mice and 11 wildtype (cd81(+/+)) littermates were anesthetized and perfused with
      paraformaldehyde. The eyes were removed and processed for examination by light
      and electron microscopy. In general, the retinas of the cd81(-/-) mice appeared
      normal. However, upon close examination, there was an 18% increase in the number
      of RPE nuclei in the cd81(-/-) mice. The photoreceptor layer of the cd81(-/-)
      mice was significantly thinner than that of the wild-type mice, even though there
      was no difference in the total thickness of the retinas in the two groups of
      mice. At the electron microscopic level we did not observe any differences in
      cell-cell junctions in the retinas of the cd81(-/-) mice as compared to their
      wild-type littermates. These data support a role for CD81 controlling cell-cycle
      and the number of RPE nuclei in the mouse retina.

PMID- 15258900
TI  - Effect of DNA loop anchorage regions (LARs) and microinjection timing on
      expression of beta-galactosidase gene injected into one-cell rabbit embryos.
AB  - The conditions favoring expression of a reporter gene microinjected into a male
      pronucleus of naturally ovulated and fertilized rabbit eggs have been studied.
      Injection of the reporter gene during S phase of the cell-cycle allows the
      highest level of expression of the gene. Incorporation of DNA loop anchorage
      regions (LARs) into constructs upstream and/or downstream of the reporter gene
      significantly increased the efficiency of expression. In all cases the expression
      of the microinjected gene started after a period of transcriptional quiescence,
      i.e., together with the expression of the host genome. Correct targeting of
      microinjected constructs within the nuclei via interaction of LAR elements with
      receptor sites on the nucleoskeleton may facilitate expression of injected DNA
      constructs as well as their integration into host cell DNA.

PMID- 15258901
TI  - In situ non-invasive spectral discrimination between bone cell phenotypes used in
      tissue engineering.
AB  - Raman micro-spectroscopy was used to discriminate between different types of bone
      cells commonly used in tissue engineering of bone, with the aim of developing a
      method of phenotypic identification and classification. Three types of bone cells
      were analysed: human primary osteoblasts (HOB), retroviral transfected human
      alveolar bone cells with SV40 large T antigen (SV40 AB), and osteoblast-like
      human osteosarcoma derived MG63 cell line. Unsupervised principal component
      analysis (PCA) and linear discriminant analysis (LDA) of the Raman spectra
      succeeded in discriminating the osteosarcoma derived MG63 cells from the non
      tumour cells (HOB and SV40 AB). No significant differences were observed between
      the Raman spectra of the HOB and SV40 AB cells, confirming the biochemical
      similarities between the two cell types. Difference spectra between tumour and
      non-tumour cells suggested that the spectral discrimination is based on the fact
      that MG63 osteosarcoma derived cells are characterised by lower concentrations of
      nucleic acids and higher relative concentrations of proteins compared to the non
      tumour bone cells. A supervised classification model (LDA) was built and showed
      high cross-validation sensitivity (100%) and specificity (95%) for discriminating
      the MG63 cells and the non-tumour cells, with 96% of the cells being correctly
      classified either as tumour or non-tumour derived cells. This study proves the
      feasibility of using Raman spectroscopy to identify in situ phenotypic
      differences in living cells.

PMID- 15258902
TI  - Volvariella volvacea lectin activates mouse T lymphocytes by a calcium dependent
      pathway.
AB  - The immunomodulatory lectin, Volvariella volvacea lectin (VVL), isolated from the
      edible mushroom, Volvariella volvacea, has been shown to stimulate the expression
      of Th1 cytokines and the proliferative activity of mouse splenocytes (She et al.
      [1998]: Biochem Biophys Res Comm 247:106-111). In order to elucidate the
      mechanisms underlying these activities, we conducted a kinetic analysis of the
      early and late activation markers in mouse T lymphocytes: (1) flow cytometric
      analysis of calcium influx, (2) induction of activation molecules (CD25 and
      CD69), (3) expression and DNA-binding activity of the nuclear factor of activated
      T cells (NFAT), NFkappaB, and activation protein-1 (AP-1), (4) translational
      production of cytokines (interleukin-2 (IL-2) and interferon-gamma (IFNgamma)),
      and (5) cell proliferation by expression of proliferating cell nuclear antigen
      (PCNA) and tritiated thymidine incorporation. All results showed that VVL induced
      a rapid expression of CD69, CD25, NFAT, IL-2, and PCNA in a dose- and time
      dependent manner, leading to lymphocyte proliferation. These effects brought
      about by VVL were more potent than those stimulated by equimolar concentrations
      of mitogenic lectin, concanavalin A (Con A). Cell activation and proliferation
      were mediated through a calcium-dependent pathway as demonstrated by a VVL
      induced increase of intracellular calcium influx, and a proliferation inhibition
      by the Ca-dependent phosphatase calcineurin blocker-cyclosporin A (CsA). Taken
      all data together, VVL is a lectin which activates lymphocyte through successive
      calcium influx, nuclear localization of NFAT transcription factor, induction of
      activation markers, CD25 and CD69, intracellular cytokine production, and cell
      proliferation.

PMID- 15258903
TI  - Vasopressin phosphorylates HSP27 in aortic smooth muscle cells.
AB  - Administration of arginine vasopressin (AVP) time-dependently induced the
      phosphorylation of heat shock protein 27 (HSP27) at Ser-15 and Ser-85 in smooth
      muscle of aorta in vivo. The AVP-induced phosphorylation of HSP27 at Ser-15 and
      Ser-85 was inhibited by a V1a receptor antagonist but not by a V2 receptor
      antagonist. In cultured aortic smooth muscle A10 cells, AVP markedly stimulated
      the phosphorylation of HSP27 at Ser-15 and Ser-85. The AVP-induced
      phosphorylation of HSP27 was attenuated by SB203580 and PD169316, inhibitors of
      p38 mitogen-activated protein (MAP) kinase, but not by PD98059, a MEK inhibitor.
      These results strongly suggest that AVP phosphorylates HSP27 via p38 MAP kinase
      in aortic smooth muscle cells.

PMID- 15258904
TI  - Dual effect of heparin on cultured adult rat cardiomyocytes.
AB  - Heparin has been widely reported to inhibit the growth of several cell types
      including neonatal rat cardiac myocyte (NRCM) but its effect on adult rat
      ventricular myocyte (ARVM) is unknown. To determine whether heparin is able to
      modulate ARVM protein synthesis capacity and if so which pathway is involved in
      this response, ARVM were cultured in presence or absence of 5% human serum and
      exposed to heparin (2-2,000 microg/ml) or its analogue xylan (0.5 and 50
      microg/ml), and either the Ca(2+) chelator BAPTA/AM (10 microg/ml), or the
      calcineurin inhibitor FK506 (10 microg/ml), and heparinase I (0.1-10 U/ml) for 2
      days. The protein synthesis (PS) was measured after 24 h incorporation of [14C]
      Phenylalanine in ARVM. Independently of the serum presence, heparin and xylan
      altered PS in a bimodal dose-dependent manner. At high doses, heparin and xylan
      (2,000 and 50 microg/ml, respectively) either had no effect (without serum) or
      inhibited PS (with serum). In absence of serum, low doses of heparin or xylan (20
      and 0.5 microg/ml, respectively) amplified the PS process in ARVM (2-fold, P <
      0.05). FK506 inhibited the trophic response to 20 microg/ml heparin alone (-39%,
      P < 0.05). In presence of serum, the heparin induced-trophic effect, that was not
      significantly altered by FK506, was inhibited by BAPTA/AM (-32%, P < 0.05).
      Finally, heparinase I that increased PS in NRCM had no effect on ARVM growth.
      This study strongly suggests that heparin dose-dependently modulated PS in ARVM,
      this result being not observed in neonatal cells. Different mechanisms involving
      intracellular Ca(2+) play a role in the PS response of ARVM to low concentrations
      of heparin, the intracellular pathways depending on the presence of serum.

PMID- 15258905
TI  - Differential control of apoptosis by DJ-1 in prostate benign and cancer cells.
AB  - DJ-1 is a conserved protein reported to be involved in diverse cellular processes
      ranging from cellular transformation, control of protein-RNA interaction,
      oxidative stress response to control of male infertility, among several others.
      Mutations in the human gene have been shown to be associated with an autosomal
      recessive, early onset Parkinson's disease (PARK7). The present study examines
      the control of DJ-1 expression in prostatic benign hyperplasia (BPH-1) and cancer
      (PC-3) cell lines in which DJ-1 abundance differs significantly. We show that
      while BPH-1 cells exhibit low basal level of DJ-1 expression, stress-inducing
      agents such as H(2)O(2) and mitomycin C markedly increase the intracellular level
      of the polypeptide. In contrast, DJ-1 expression is relatively high in PC-3
      cells, and incubation with the same cytotoxic drugs does not modulate further the
      level of the polypeptide. In correlation with the expression of DJ-1, both
      cytotoxic agents activate the apoptotic pathway in the prostatic benign cells but
      not in PC-3 cells, which are resistant to their action. We further demonstrate
      that incubation of BPH-1 cells with TNF-related-apoptosis-inducing-ligand/Apo-2L
      (TRAIL) also enhances DJ-1 expression and that TRAIL and H(2)O(2) act additively
      to stimulate DJ-1 accumulation but synergistically in the activation of the
      apoptotic pathway. Time-course analysis of DJ-1 stimulation shows that while DJ-1
      level increases without significant lag in TRAIL-treated cells, there is a delay
      in H(2)O(2)-treated cells, and that the increase in DJ-1 abundance precedes the
      activation of apoptosis. Unexpectedly, over-expression of DJ-1 de-sensitizes BPH
      1 cells to the action of apoptotic-inducing agents. However, RNA-interference
      mediated silencing of DJ-1 expression results in sensitization of PC-3 cells to
      TRAIL action. These results are consistent with a model in which DJ-1 is involved
      in the control of cell death in prostate cell lines. DJ-1 appears to play a
      differential role between cells expressing a low but inducible level of DJ-1
      (e.g., BPH-1 cells) and those expressing a high but constitutive level of the
      polypeptide (e.g., PC-3 cells).

PMID- 15258906
TI  - In vitro and in vivo prevention of HIV protease inhibitor-induced insulin
      resistance by a novel small molecule insulin receptor activator.
AB  - Protease inhibitor (PI) therapy for the treatment of patients infected with human
      immunodeficiency virus is frequently associated with insulin resistance and
      diabetic complications. These adverse effects of PI treatment result to a large
      extent from their inhibition of insulin-stimulated glucose transport. Insulin
      receptor (IR) activators that enhance the insulin signaling pathway could be
      effective in treating this resistance. However, there are no agents reported that
      reverse inhibition of insulin action by PIs. Herein, we describe the effects of
      TLK19781. This compound is a non-peptide, small molecule, activator of the IR. We
      now report in cultured cells, made insulin resistant HIV by PI treatment, that
      TLK19781 both increased the content of insulin-stimulated GLUT4 at the plasma
      membrane, and enhanced insulin-stimulated glucose transport. In addition, oral
      administration of TLK19781 with the PI, indinavir improved glucose tolerance in
      rats made insulin resistant. These results suggest, therefore, that IR activators
      such as TLK19781 may be useful in treating the insulin resistance associated with
      PIs.

PMID- 15258907
TI  - Heme oxygenase-1 protects against apoptosis induced by tumor necrosis factor
      alpha and cycloheximide in papillary thyroid carcinoma cells.
AB  - Heme oxygenase-1 (HO-1) plays a role in the resistance to apoptosis of several
      types of cells, but its role in the development of thyroid cancer is unknown. In
      this study, we investigated the regulation of HO-1 in human papillary thyroid
      carcinoma cells (KAT5). The results show that HO-1 is significantly induced by
      hemin and cadmium. In addition to inducing HO-1, hemin and cadmium also cause a
      rise in the levels of p21, a cyclin-dependent kinase inhibitor. Cells with
      increased levels of HO-1 and p21 were more resistant to apoptotic stimuli than
      cells with normal levels. The cells resistant to apoptosis also displayed an
      increased arrest at the G(0)/G(1) phase of the cell-cycle. The induced levels of
      HO-1 and p21 were significantly reduced by p38 mitogen-activated protein kinase
      (p38 MAPK) and extracellular-regulated kinase (ERK) inhibitors. More importantly,
      KAT5 cells regained their sensitivity to apoptotic stimuli after they were
      treated with these kinase inhibitors, indicating that p38 MAPK and ERK are
      required for the resistance to apoptosis conferred by HO-1. Furthermore, we
      demonstrated that increased levels of HO-1 and p21 expression are associated with
      an increase in the activity of NF-kappaB and that inhibiting NF-kappaB leads to a
      block in the induction of HO-1 and p21. In summary, this study reveals that an
      increase in the level of HO-1 markedly reduces the sensitivity of papillary
      thyroid carcinoma cells to apoptotic stimuli. The HO-1 pathway of apoptosis
      resistance is associated with an increase in the levels of p21, involves a p38
      MAPK and ERK-mediated mechanism and can be suppressed by inhibiting NF-kappaB.

PMID- 15258908
TI  - Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the
      JNK/p38-Bax-dependent mitochondrial pathway.
AB  - Death-associated protein (Daxx) deletion mutant (aa 501-625) has been known to be
      an inducer of apoptosis. In this study, we observed that the Bax-dependent
      mitochondrial death signaling pathway plays an important role in Daxx501-625
      induced apoptosis. Daxx fragment-induced activation of caspase-9 and -3 was
      mediated through the apoptosis signal-regulating kinase 1 (ASK1)-MEK-c-Jun-N
      terminal kinase (JNK)/p38-Bax pathway. By overexpressing JNK-binding domain (JBD)
      of JIP1, a JNK-inhibitory protein, and treatment with SB203580, a specific p38
      inhibitor, DU-145 cells were made resistant to Daxx501-625-induced apoptosis.
      Capase-3 deficiency, Bax deficiency, or overexpression of a dominant-negative
      caspase-9 mutant prevented apoptosis, even though the Daxx501-625 fragment still
      activated the ASK1-MEK-MAPK pathway. Interestingly, Daxx501-625-induced Bcl-2
      interacting domain (Bid) cleavage was suppressed in the dominant-negative caspase
      9 mutant cells, whereas Bim was still phosphorylated in these cells. These
      results suggest that cleavage of Bid occurs downstream of caspase-9 activation.
      In contrast, phosphorylation of Bim is upstream of caspase-9 activation. Taken
      together, our results suggest that Daxx501-625-induced apoptosis is mediated
      through the ASK1-MEK-JNK/p38-Bim-Bax-dependent caspase pathway.

PMID- 15258909
TI  - Soluble form of Jagged1: unique product of epithelial keratinocytes and a
      regulator of keratinocyte differentiation.
AB  - Notch signaling pathway is an important regulator of epithelial differentiation.
      Recent studies have characterized multiple ligands, including Jagged1, as
      mediators of Notch signaling. In this work, an alternatively spliced transcript
      of Jagged1 was isolated in yeast two-hybrid screening through interaction with
      thrombospondin-1. This transcript, devoid of sequences encoding the transmembrane
      and intracellular domains of Jagged1, was specific for keratinocytes.
      Furthermore, the truncated Jagged1 polypeptide devoid of the intracellular domain
      was detected prominently in the suprabasal keratinocyte layer in neonatal
      epithelia. The soluble form of Jagged1, when expressed as a tagged polypeptide
      was efficiently secreted into the culture medium and the N-terminal signal
      sequence became cleaved off upon secretion. Direct contact between a cell
      presenting the transmembrane form of Jagged1 and a Notch-expressing cell has been
      proposed as a prerequisite for the signaling event. However, the soluble form of
      Jagged1, when present in the cell culture medium, was sufficient to induce
      keratinocyte differentiation. These observations suggest a novel mechanism of how
      Jagged1 can target cells beyond the direct cell-cell contact in developing
      epithelia.

PMID- 15258910
TI  - Expression and DNA-binding activity of MYCN/Max and Mnt/Max during induced
      differentiation of human neuroblastoma cells.
AB  - Amplification of MYCN is one of the most important prognostic markers for
      neuroblastoma and is correlated with rapid tumor progression and poor prognosis.
      MYCN belongs to the Myc/Max/Mad/Mnt network of proteins that regulate
      proliferation, apoptosis, and differentiation. It is well established that MYCN
      is downregulated during induced differentiation of neuroblastoma cells carrying
      an amplified MYCN gene, but very little is known about other components of the
      network, i.e., the Max, Mad, and Mnt proteins, during this process. In this study
      we show that Mad and Mnt expression was only modestly regulated in
      differentiating SK-N-BE(2) neuroblastoma cells, while MYCN was rapidly
      downregulated. This downregulation was reflected in a decreased MYCN/Max DNA
      binding activity while the Mnt/Max binding did not change during differentiation.
      In parallel experiments we also analyzed the Myc/Max/Mad expression and DNA
      binding capacity during induced differentiation in the MYCN single copy
      neuroblastoma cell line SH-SY5Y. In this cell line only modest changes in
      expression of the components of the MYCN/Max/Mad/Mnt network was detected, but
      since the cell line expresses relatively low levels of MYCN and c-Myc, these
      changes might be of functional significance. Cell cycle analyses of SK-N-BE(2)
      demonstrated an increase in the G1-phase fraction after RA-treatment. These data
      show that the decreased MYCN expression and MYCN DNA-binding is correlated with
      retarded cell cycle progression. Furthermore, when Mad1 or Mnt was overexpressed
      in SK-N-BE(2) cells they retained the capacity to differentiate, underscoring the
      notion that MYCN downregulation, and not changes in Mad/Mnt expression, is
      essential for neuroblastoma cell differentiation.

PMID- 15258911
TI  - Lysophospholipids and their G protein-coupled receptors in biology and diseases.

PMID- 15258912
TI  - Metabolic pathways and physiological and pathological significances of lysolipid
      phosphate mediators.
AB  - Lysophosphatidic acid and sphingosine 1-phosphate are structurally simple and
      physiologically very important lysophospholipids. Because they possess distinct
      structural backbones (glycerol and sphingosine, respectively), there are
      different metabolic pathways for their intracellular production. Recently,
      several key enzymes that produce or degrade these lysolipid phosphate mediators
      extracellularly have been characterized. This review focuses on the physiological
      and pathophysiological significances of the extracellular metabolic pathways
      involving recently characterized exo-type lysophospholipase D, ecto-type
      phospholipase A, and ecto-type lipid phosphate phosphatase.

PMID- 15258913
TI  - Generation and metabolism of bioactive sphingosine-1-phosphate.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lysosphingophospholipid that has
      been implicated in the regulation of vital biological processes. Abundant
      evidence indicates that S1P acts as both an intracellular messenger and an
      extracellular ligand for a family of five specific G protein-coupled S1P
      receptors (S1PRs). Cellular levels of S1P are tightly regulated in a spatio
      temporal manner through its synthesis catalyzed by sphingosine kinases (SphKs)
      and degradation by S1P lyase (SPL) and specific S1P phosphohydrolases. Over the
      past decade, the identification and cloning of genes encoding S1P metabolizing
      enzymes has increased rapidly. Overexpression and deletion of these enzymes has
      provided important insights into the intracellular and the "inside-out" functions
      of S1P. The purpose of this review is to summarize the current knowledge of S1P
      metabolizing enzymes, their enzymatic properties, and their roles in the control
      of cellular functions by S1P.

PMID- 15258914
TI  - Lipid phosphate phosphatases and related proteins: signaling functions in
      development, cell division, and cancer.
AB  - Lipid phosphates initiate key signaling cascades in cell activation.
      Lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are produced by
      activated platelets. LPA is also formed from circulating lysophosphatidylcholine
      by autotaxin, a protein involved tumor progression and metastasis. Extracellular
      LPA and S1P stimulate families of G-protein coupled receptors that elicit diverse
      responses. LPA is involved in wound repair and tumor growth. Exogenous S1P is a
      potent stimulator of angiogenesis, a process vital in development, tissue repair
      and the growth of aggressive tumors. Inside the cell, phosphatidate (PA),
      ceramide 1-phosphate (C1P), LPA, and S1P act as signaling molecules with distinct
      functions including the stimulation of cell division, cytoskeletal rearrangement,
      Ca(2+) transients, and membrane movement. These observations imply that
      phosphatases that degrade lipid phosphates on the cell surface, or inside the
      cell, regulate cell signaling under physiological and pathological conditions.
      This occurs through attenuation of signaling by the lipid phosphates and by the
      production of bioactive products (diacylglycerol, ceramide, and sphingosine).
      Three lipid phosphate phosphatases (LPPs) and a splice variant dephosphorylate
      LPA, PA, CIP, and S1P. Two S1P phosphatases (SPPs) act specifically on S1P. In
      addition, there is family of four LPP-related proteins (LPRs, or plasticity
      related genes, PRGs). PRG-1 expression in neurons has been reported to increase
      extracellular LPA breakdown and attenuate LPA-induced axonal retraction. It is
      unclear whether the LRPs dephosphorylate LPA directly, stimulate LPP activity, or
      bind LPA and S1P. Also, the importance of extra- versus intra-cellular actions of
      the LPPs and SPPs, and the individual roles of different isoforms is not firmly
      established. Understanding the functions and regulation of the LPPs, SPPs and
      related proteins will hopefully contribute to interventions to correct
      dysfunctions in conditions such as wound repair, inflammation, angiogenesis,
      tumor growth, and metastasis.

PMID- 15258915
TI  - Structural and functional characteristics of S1P receptors.
AB  - The sphingosine-1-phosphate (S1P) family of G protein-coupled receptors (GPCR)
      regulates essential cellular processes such as proliferation, migration,
      cytoskeletal organization, adherens junction assembly, and morphogenesis. S1P, a
      product from the breakdown of sphingomyelin, binds to the five members of this
      receptor family, S1P(1), S1P(2), S1P(3), S1P(4), and S1P(5), previously referred
      to as endothelial differentiation gene (EDG)-1, -5, -3, -6, and -8. S1P receptors
      are widely expressed in different tissues, so it is not surprising that the S1P
      receptor family regulates many physiological processes, such as vascular
      maturation, cardiac development, lymphocyte trafficking, and vascular
      permeability. FTY720, a new S1P receptor agonist, is undergoing clinical trials
      as an immunosuppressor. Understanding the physiological role of these receptors
      and the basics of the ligand-receptor interaction will potentially provide new
      therapies to control a variety of diseases.

PMID- 15258916
TI  - Novel clusters of receptors for sphingosine-1-phosphate,
      sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for
      "old" ligands.
AB  - The (lyso)phospholipid mediators sphingosine-1-phosphate (S1P), lysophosphatidic
      acid (LPA), sphingosylphosphorylcholine (SPC), and phosphatidic acid (PA)
      regulate diverse cellular responses such as proliferation, survival and death,
      cytoskeletal rearrangements, cell motility, and differentiation among many
      others. Signaling is complex and many signaling events are mediated through the
      activation of cell surface seven transmembrane (7TM) G protein coupled receptors.
      Five high affinity receptors for S1P have been identified so far and named S1P(1,
      2,3,4,5) (formerly referred to as endothelial differentiation gene (edg)1, 5, 3,
      6, 8). Recently, the orphan receptor GPR63 was identified a low affinity S1P
      receptor structurally distant from the S1P(1-5) family. The orphan GPR3, 6, 12
      cluster, phylogenetically related to the edg and melanocortin receptors appears
      to be subject to modulation by S1P and SPC although all three receptors are
      strong constitutive stimulators of the Galphas-adenylyl cyclase (AC) pathway and
      would not require additional ligand stimulation but rather inverse agonism to
      control activity. Ovarian cancer G protein coupled receptor 1 (OGR1) and GPR4,
      two structurally closely related receptors were assigned in functional and
      binding studies as high affinity molecular targets for SPC. Very recently,
      however, both OGR1 and GPR4 were described as receptors endowed with the ability
      to signal cells in response to protons. LPA exerts its biological effects through
      the activation of G protein coupled LPA(1-3) receptors (formerly referred to as
      edg2, 4, 7). A fourth high affinity LPA receptor has been identified: P2Y9
      (GPR23) structurally related to nucleotide receptors and phylogenetically quite
      distant from the high affinity LPA(1-3) cluster. This review attempts to give an
      overview about the existing families of lysophosholipid receptors and the
      spectrum of lipid agonists they use as high or low affinity ligands to relay
      extracellular signals into intracellular responses. Recently deorphaned lipid
      receptors, within and outside the known lipid receptor clusters will receive
      particular attention.

PMID- 15258917
TI  - Lysophospholipid receptor-dependent and -independent calcium signaling.
AB  - Changes in cellular Ca(2+) concentrations form a ubiquitous signal regulating
      numerous processes such as fertilization, differentiation, proliferation,
      contraction, and secretion. The Ca(2+) signal, highly organized in space and
      time, is generated by the cellular Ca(2+) signaling toolkit. Lysophospholipids,
      such as sphingosine-1-phosphate (S1P), sphingosylphosphorylcholine (SPC), or
      lysophosphatidic acid (LPA) use this toolkit in a specific manner to initiate
      their cellular responses. Acting as agonists at G protein-coupled receptors, S1P,
      SPC, and LPA increase the intracellular free Ca(2+) concentration ([Ca(2+)](i))
      by using the classical, phospholipase C (PLC)-dependent pathway as well as PLC
      independent pathways such as sphingosine kinase (SphK)/S1P. The S1P(1) receptor,
      via protein kinase C, inhibits the [Ca(2+)](i) transients caused by other
      receptors. Both S1P and SPC also act intracellularly to regulate [Ca(2+)](i).
      Intracellular S1P mobilizes Ca(2+) in intact cells independently of G protein
      coupled S1P receptors, and Ca(2+) signaling by many agonists requires SphK
      mediated S1P production. As shown for the FcepsilonRI receptor, PLC and SphK may
      contribute specific components to the overall [Ca(2+)](i) transient. Of the many
      open questions, identification of the intracellular S1P target site(s) appears to
      be of particular importance.

PMID- 15258918
TI  - G protein mediated signaling pathways in lysophospholipid induced cell
      proliferation and survival.
AB  - Agonist activation of a subset of G protein coupled receptors (GPCRs) stimulates
      cell proliferation, mimicking the better known effects of tyrosine kinase growth
      factors. Cell survival or apoptosis is also regulated via pathways initiated by
      stimulation of these same GPCRs. This review focuses on aspects of signaling by
      the lysophospholipid mediators, lysophosphatidic acid (LPA), and sphingosine 1
      phosphate (S1P), which make these agonists uniquely capable of modulating cell
      growth and survival. The general features of GPCR coupling to specific G
      proteins, downstream effectors and signaling cascades are first reviewed. GPCR
      coupling to G(i) and Ras/MAPK or to G(q) and phospholipase generated second
      messengers are insufficient to regulate cell proliferation while G(12/13)/Rho
      engagement provides additional complementary signals required for cell
      proliferation. Survival is best predicted by coupling to G(i) pathways that
      regulate PI3K and Akt, but other signals generated through different G protein
      pathways are also implicated. The unique ability of LPA and S1P to concomitantly
      stimulate G(i), G(q), and G(12/13) pathways, given the proper complement of
      expressed LPA or S1P receptors, allows these receptors to support cell survival
      and proliferation. In pathophysiological situations, e.g., vascular disease,
      cancer, brain injury, and inflammation, components of the signaling cascade
      downstream of lysophospholipid receptors, in particular those involving Ras or
      Rho, may be altered. In addition, up or downregulation of LPA or S1P receptor
      subtypes, altering their ratio, and increased availability of the
      lysophospholipid ligands at sites of injury or inflammation, likely contribute to
      disease and may be important targets for therapeutic intervention.

PMID- 15258919
TI  - Lysophospholipids in development: Miles apart and edging in.
AB  - Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are endogenous
      bioactive lipids that participate in the regulation of mammalian cell
      proliferation, apoptosis, migration, and angiogenesis. These processes are each
      critical for successful embryogenesis, raising the possibility that
      lysophospholipid signaling may contribute to normal animal development. In fact,
      recent studies in developmental model systems have established that S1P and LPA
      are necessary for diverse developmental programs including those required for
      morphogenesis of vertebrate reproductive, cardiovascular and central and
      peripheral nervous systems (PNS), as well as the establishment of maternal-fetal
      circulation and the immune system. Genetic, morphological, and biochemical
      characterization of developmental model systems offer powerful approaches to
      elucidating the molecular mechanisms of lysophospholipid signaling and its
      contributions to animal development and postnatal physiology. In this review, the
      routes of S1P and LPA metabolism and our current understanding of
      lysophospholipid-mediated signal transduction in mammalian cells will be
      summarized. The evidence implicating lysophospholipid signaling in the
      development of specific vertebrate systems will then be reviewed, with an
      emphasis on signals mediated through G protein-coupled receptors of the Edg
      family. Lastly, recent insights derived from the study of simple metazoan models
      and implications regarding lysophospholipid signaling in organisms in which Edg
      receptors are not conserved will be explored.

PMID- 15258920
TI  - LPA in neural cell development.
AB  - Lysophosphatidic acid (LPA) elicits diverse cellular responses through cell
      surface LPA receptors in nervous system-derived cells and cell lines. The
      developing nervous system is one of the major loci for LPA receptor expression.
      Recent studies have also revealed that metabolic pathways of LPA are present in
      the nervous system. A growing body of literature suggests a crucial role for LPA
      in neuronal development processes, including neurogenesis, neuronal migration,
      neuritogenesis, and myelination.

PMID- 15258921
TI  - Genetics and cell biology of lysophosphatidic acid receptor-mediated signaling
      during cortical neurogenesis.
AB  - Lysophosphatidic acid (LPA) is a small lysophospholipid that signals through G
      protein coupled receptors (GPCRs) to mediate diverse cellular responses. Two LPA
      receptors, LPA(1) and LPA(2), show gene expression profiles in mouse embryonic
      cerebral cortex, suggesting roles for LPA signaling in cerebral cortical
      development. Here, we review loss-of-function and gain-of-function models that
      have been used to examine LPA signaling. Genetic deletion of lpa(1) or both
      lpa(1) and lpa(2) in mice results in 50-65% neonatal lethality, but not obvious
      cortical phenotypes in survivors, suggesting that compensatory signaling systems
      exist for regulating cortical development. A gain-of-function model, approached
      by increasing receptor activation through exogenous delivery of LPA, shows that
      LPA signaling regulates cerebral cortical growth and anatomy by affecting
      proliferation, differentiation and cell survival during embryonic development.

PMID- 15258922
TI  - Radiation-induced genomic instability: a role for secreted soluble factors in
      communicating the radiation response to non-irradiated cells.
AB  - Radiation induced genomic instability can be described as the increased rate of
      genomic alterations occurring in the progeny of an irradiated cell. Its
      manifestations are the dynamic ongoing production of chromosomal rearrangements,
      mutations, gene amplifications, transformation, microsatellite instability,
      and/or cell killing. In this prospectus, we present the hypothesis that cellular
      exposure to ionizing radiation can result in the secretion of soluble factors by
      irradiated cells and/or their progeny, and that these factors can elicit
      responses in other cells thereby initiating and perpetuating ongoing genomic
      instability.

PMID- 15258923
TI  - Locus of fragility in robust breast cancer system.
AB  - Functional heterogeneous redundancy of breast cancer makes this tumor to be
      robust. Signaling mechanisms which control cancer responses are crucial for
      controlling robustness. Identification of locus of fragility in cancer represents
      basic mechanism to target robustness. The goal of this prospect is to present
      locus of fragility in breast cancer robust system, and how disruption of this
      locus induces failure of robustness. My recent research show, that locus of
      fragility in breast cancer cells is suppression of nitric oxide (NO). When it was
      targeted, dynamics of cancer to generate robustness failed that it blocked cancer
      cell proliferation dependent on the NO/Rb pathway, blocked cell migration and
      angiogenesis dependent on the VEGF/PI3K/AKT/NO/ICAM-1 pathway, and induced breast
      cancer cell apoptosis through the NO/ROCK/FOXO3a signaling pathway. This tiny and
      trivial perturbation in breast cancer cells such as suppression of NO represents
      locus of fragility (weakness) and new approach for breast cancer chemotherapy.

PMID- 15258924
TI  - Ime2p and Cdc28p: co-pilots driving meiotic development.
AB  - Meiosis can be considered an elaboration of the cell division cycle in the sense
      that meiosis combines cell-cycle processes with programs specific to meiosis.
      Each phase of the cell division cycle is driven forward by cell-cycle kinases
      (Cdk) and coordinated with other phases of the cycle through checkpoint
      functions. Meiotic differentiation is also controlled by these two types of
      regulation; however, recent study in the budding yeast S. cerevisiae indicates
      that progression of meiosis is also controlled by a master regulator specific to
      meiosis, namely the Ime2p kinase. Below, I describe the overlapping roles of
      Ime2p and Cdk during meiosis in yeast and speculate on how these two kinases
      cooperate to drive the progression of meiosis.

PMID- 15258926
TI  - Expression and function of periostin-isoforms in bone.
AB  - Periostin was originally identified in MC3T3-E1 osteoblast-like cells. We have
      identified an isoform of periostin referred to as periostin-like-factor (PLF). It
      is homologous to other proteins such as fasciclin I (fas I), MPB70, betaIG-H3,
      and Algal-CAMs. All of these proteins are implicated in regulating cell adhesion.
      PLF and the other isoforms of periostin differ in their C-terminal sequences. PLF
      and periostin differ in two specific regions, between 673 and 699 amino acids
      (aa) and 785-812 aa. Periostin isoforms are expressed in vivo and in vitro during
      the stages of osteoblast differentiation and maturation. Their mRNAs are present
      in pre-osteoblast cells as detected by in situ hybridization, and the proteins
      are between 86 and 93 kD in size as determined by Western blot analysis.
      Antisense oligonucleotides and antibodies directed against the isoforms of
      periostin were used to block the activity of these proteins. In both cases, the
      levels of osteoblast-specific-differentiation markers were markedly reduced
      suggesting a role for these proteins in osteoblast differentiation.

PMID- 15258925
TI  - A(3) adenosine receptor deficiency does not influence atherogenesis.
AB  - Atherosclerosis is a multifactorial disease, the progression of which is
      modulated by several factors, including inflammation and hypercholesterolemia.
      The A(3) adenosine receptor (A(3)AR) has been reported to affect mast cell
      degranulation leading to inflammation, as well as to influence cardiovascular
      homeostasis. Here, we show that its deletion can also impact vascular smooth
      muscle cell (VSMC) proliferation in vitro. Based on these observations, we
      hypothesized that A(3)AR deficiency would affect atheromatous lesion development
      in vivo. Our results indicate that the expression of the matrix enzyme lysyl
      oxidase (LO) is increased while the proliferation potential of VSMC is decreased
      in A(3)AR-null aortas. This is in accordance with the previously reported inverse
      correlation between LO level and proliferation. Nevertheless, we found that A(3)
      deficiency does not protect vessels against atherogenesis. This was demonstrated
      in mouse models of high fat diet-induced atherosclerosis and guidewire-induced
      femoral artery injury. We conclude that the contributions of the A(3)AR to
      inflammation and to modulating LO levels are not significant enough to control
      vascular response to injury.

PMID- 15258933
TI  - When chemistry met biology.

PMID- 15258927
TI  - Mitochondrial P2Y-Like receptors link cytosolic adenosine nucleotides to
      mitochondrial calcium uptake.
AB  - ATP is a known extracellular ligand for cell membrane purinergic receptors.
      Intracellular ATP can work also as a regulatory ligand via binding sites on
      functional proteins. We report herein the existence of P2Y(1)-like and P2Y(2)
      like receptors in hepatocyte mitochondria (mP2Y(1) and mP2Y(2)), which regulate
      mCa(2+) uptake though the uniporter. Mitochondrial P2Y(1) activation stimulates
      mCa(2+) uptake; whereas, mP2Y(2) activation inhibits mCa(2+) uptake. ATP acts
      preferentially on mP2Y(2) receptors, while ADP and AMP-PNP stimulate both the
      mP2Y(1) and mP2Y(2). PPADS inhibits ADP stimulated mP2Y(1)-mediated mCa(2+)
      uptake. In addition, UTP, a selective P2Y(2) agonist, strongly inhibits mCa(2+)
      uptake. The newly discovered presence and function of these receptors is
      significant because it explains increased mCa(2+) uptake in the setting of low
      cytosolic [ATP] and, therefore, establishes a mechanism for direct feedback in
      which cytosolic [ATP] governs mitochondrial ATP production through regulation of
      mCa(2+) uptake.

PMID- 15258934
TI  - Two birds with one metallic stone: single-pot catalysis of fundamentally
      different transformations.
AB  - Advances in metal catalysis have revolutionized organic synthesis, with the scope
      of metal-catalyzed reactions now covering nearly all areas of carbon-carbon,
      carbon-hydrogen, and carbon-heteroatom bond formation. For years, the goal was to
      develop catalysts that were highly selective for a single transformation.
      However, a promising current area of research is the use of a single catalyst to
      mediate more than one transformation in a selective manner. Whereas much early
      work was focused on using a catalyst for several similar transformations, recent
      investigations have shown that it is also possible to employ a single catalyst
      for several very different transformations in a single reaction sequence. This
      Minireview focuses on methods in which the mechanisms of the transformations are
      fundamentally very different.

PMID- 15258935
TI  - Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers.
AB  - This review addresses the fabrication and properties of novel polyelectrolyte
      microcapsules, with an emphasis on their mechanical and permeability properties.
      Ease of preparation through layer-by-layer self assembly, accurate control over
      wall thickness as well as flexibility in the choice of constituents make these
      capsules very promising for numerous applications in materials and life science.
      Moreover, by engineering the inner and outer interfaces, these capsules can be
      used as microreactors for precipitation, crystallization, and polymerization
      reactions, as well as enzymatic, and heterogeneous catalysis.

PMID- 15258936
TI  - Stereospecific and stereodivergent construction of quaternary carbon centers
      through switchable directed/nondirected allylic substitution.

PMID- 15258937
TI  - Iterative deoxypropionate synthesis based on a copper-mediated directed allylic
      substitution.

PMID- 15258938
TI  - Two metal ions coordinated to a purine residue tolerate each other well.

PMID- 15258939
TI  - Cobalt(I)-catalyzed asymmetric [2+2+2] cycloaddition of alkynes and nitriles:
      synthesis of enantiomerically enriched atropoisomers of 2-arylpyridines.

PMID- 15258940
TI  - Highly sensitive protease assay using fluorescence quenching of peptide probes
      based on photoinduced electron transfer.

PMID- 15258941
TI  - Fabrication of polymer nanofibers and carbon nanofibers by using a salt-assisted
      microemulsion polymerization.

PMID- 15258942
TI  - Enzyme microarrays: On-chip determination of inhibition constants based on
      affinity-label detection of enzymatic activity.

PMID- 15258943
TI  - Supramolecular control over the stereochemistry of diene polymers.

PMID- 15258944
TI  - A molecular ball bearing mediated by multiligand exchange in concert.

PMID- 15258946
TI  - Synthesis and structure of [Ag26In18S36Cl6(dppm)10(thf)4][InCl4(thf)]2--a
      combined approach of theory and experiment.

PMID- 15258947
TI  - Ga2O3 and GaN semiconductor hollow spheres.

PMID- 15258945
TI  - The C-glycoside analogue of the immunostimulant alpha-galactosylceramide
      (KRN7000): synthesis and striking enhancement of activity.

PMID- 15258948
TI  - Polyhedral ferrous and ferric siloxanes.

PMID- 15258949
TI  - Electron transfer in a Hg-SAM//SAM-Hg junction mediated by redox centers.

PMID- 15258950
TI  - Dehydroxylation route to surface modification of mesoporous silicas by using
      grignard reagents.

PMID- 15258951
TI  - Molecular [(SnO)6] trapped by two [R2Si2O3] fragments: X-ray single-crystal
      structure of [(SnO)6(R2Si2O3)2].

PMID- 15258952
TI  - Transition-metal-catalyzed reactions involving imidazolium salt/N-heterocyclic
      carbene couples as substrates.

PMID- 15258953
TI  - A dimetallic cage with a long ellipsoidal cavity for the fluorescent detection of
      dicarboxylate anions in water.

PMID- 15258954
TI  - Kinetic control over the thermal stability of the In-H bond: synthesis and
      characterization of amido indium hydride complexes.

PMID- 15258956
TI  - Population and group structure of western lowland gorillas (Gorilla gorilla
      gorilla) at Lokoue, Republic of Congo.
AB  - During a 17-month study at the Lokoue clearing in Odzala National Park, Republic
      of Congo, we identified 377 western lowland gorillas. This population included 31
      solitary males, 37 breeding groups, and eight nonbreeding groups. Its age- and
      sex-class structure was similar to those observed at two other clearings in the
      same forest block. However, the size of breeding groups varied with site (either
      clearing or forest sites). At Lokoue, breeding groups (mean size: 8.2 gorillas;
      range: 3-15) included a single silverback male and, on average, 3.2 adult
      females. Nonbreeding groups (mean size: 5.5; range: 2-15) were devoid of adult
      females. Five of the nonbreeding groups were composed predominantly of
      blackbacks, subadult males, and juveniles, and thus fit the definition of all
      male groups previously observed in mountain gorillas. Our study confirms that 1)
      one-male breeding groups are the norm in western gorillas, and 2) all-male groups
      occur in this species. Despite frequent changes in members due to migrations of
      the males, the persistence of these all-male groups indicates that they may play
      an important role in the life of migrating males. Variations in population
      structure, and group composition and type among gorilla populations are
      discussed. However, a further understanding of the evolution of group-living in
      gorillas requires detailed ecological studies conducted in parallel with studies
      of the population structure and dynamics of these groups.

PMID- 15258957
TI  - Ecological correlates of abundance in the Tana mangabey (Cercocebus galeritus).
AB  - I investigated the ecological correlates of abundance in the Tana mangabey
      (Cercocebus galeritus), one of the world's most endangered primates, with the
      goal of recommending management strategies. I systematically selected 31 forest
      fragments throughout the mangabey's 60-km distribution along the lower Tana River
      in southeastern Kenya. Within the 31 fragments, I measured vegetation structure,
      food abundance, and human forest product use in 107 belt transects, and conducted
      370 mangabey surveys. I used a weighted multiple regression analysis to determine
      whether there was a dependence between the selected forest attributes and the
      mean number of mangabey groups per fragment. Fragment area and density of trees >
      or =10 cm diameter at breast height (DBH) were the only variables that
      significantly correlated with the variation in mangabey abundance. No additional
      variables were significant when the analysis was limited to forest fragments
      inside the Tana River Primate National Reserve (TRPNR) or to fragments outside
      the TRPNR. When I estimated the resources available before recent human forest
      product use by adding nonharvested and harvested variables, the total basal area
      of the top 15 food species became significant. This was only within the TRPNR,
      however. Management, therefore, should focus on increasing forest area, density
      of trees > or =10 cm DBH, and coverage of food trees throughout the mangabey's
      distribution. Solutions must be found for the problem of forest clearing, and
      forest product use must be better managed to protect the habitat of this
      critically endangered primate. The significance of food abundance only within the
      TRPNR suggests a need to collect dietary data from mangabey groups in fragments
      toward the southern limit of the mangabey's distribution, where plant species
      composition differs from that in fragments in which dietary data have been
      previously collected.

PMID- 15258958
TI  - Nuclear integrations of mitochondrial DNA in gorillas.
AB  - Great ape systematics, particularly at the species level and below, is currently
      under debate, due in part to the recent influx of molecular data. The phylogenies
      of previously published mitochondrial control region (or D-loop) DNA sequences in
      gorillas show deep splits within West African gorillas (Gorilla gorilla gorilla),
      and very high levels of nucleotide diversity in this subspecies. Here we
      demonstrate that several previously reported D-loop haplotypes from West African
      gorillas are in all likelihood nuclear integrations of mitochondrial DNA. Revised
      estimates of the amount and pattern of mitochondrial DNA diversity in gorillas
      are provided, revealing two reciprocally monophyletic and highly divergent groups
      of gorillas, concurrent with their geographic distribution.

PMID- 15258959
TI  - Brain structure variation in great apes, with attention to the mountain gorilla
      (Gorilla beringei beringei).
AB  - This report presents data regarding the brain structure of mountain gorillas
      (Gorilla beringei beringei) in comparison with other great apes. Magnetic
      resonance (MR) images of three mountain gorilla brains were obtained with a 3T
      scanner, and the volume of major neuroanatomical structures (neocortical gray
      matter, hippocampus, thalamus, striatum, and cerebellum) was measured. These data
      were included with our existing database that includes 23 chimpanzees, three
      western lowland gorillas, and six orangutans. We defined a multidimensional space
      by calculating the principal components (PCs) from the correlation matrix of
      brain structure fractions in the well-represented sample of chimpanzees. We then
      plotted data from all of the taxa in this space to examine phyletic variation in
      neural organization. Most of the variance in mountain gorillas, as well as other
      great apes, was contained within the chimpanzee range along the first two PCs,
      which accounted for 61.73% of the total variance. Thus, the majority of
      interspecific variation in brain structure observed among these ape taxa was no
      greater than the within-species variation seen in chimpanzees. The loadings on
      PCs indicated that the brain structure of great apes differs among taxa mostly in
      the relative sizes of the striatum, cerebellum, and hippocampus. These findings
      suggest possible functional differences among taxa in terms of neural adaptations
      for ecological and locomotor capacities. Importantly, these results fill a
      critical gap in current knowledge regarding great ape neuroanatomical diversity.

PMID- 15258960
TI  - Seasonal variations in the activity budget of Japanese macaques in the coniferous
      forest of Yakushima: effects of food and temperature.
AB  - Seasonal variations in the activity budget of Japanese macaques in the coniferous
      forest of Yakushima were studied over the course of 1 year. On an annual basis,
      they spent 38% of the daytime feeding, 16% traveling, 14% in social interactions,
      and 32% engaged in resting. The effects of temperature and food-related factors
      (i.e., food distribution, feeding speed, and food abundance) on the seasonal
      variations of activity budget were examined by stepwise multiple regression
      analysis. When the temperature was low, the macaques decreased traveling and
      feeding time, in accordance with the prediction that endothermal animals save
      energy under severe thermoregulatory cost. When the feeding speed of available
      foods was slow, they spent more time feeding. When high-quality foods were
      abundant, they decreased feeding time. These macaques did not respond to
      fluctuations in food distribution. The present results indicate the importance of
      temperature, in addition to food-related factors, as a determinant of activity
      budgets.

PMID- 15258961
TI  - Persistent infection of SARS coronavirus in colonic cells in vitro.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) can produce
      gastrointestinal symptoms. The intestinal tract is the only extrapulmonary site
      where viable viruses have been detected. This study examined seven established
      human intestinal cell lines, DLD-1, HCT-116, HT-29, LoVo, LS-180, SW-480 and SW
      620, for their permissiveness to SARS-CoV infection. The results showed that only
      LoVo cells were permissive to SARS-CoV infection as evident by positive findings
      from indirect immunofluorescence staining for intracellular viral antigens, in
      situ hybridization for intracellular viral RNA, and electron microscopy for
      intracellular viral particles. In contrast to Vero cells, SARS-CoV did not
      produce cytopathic effects on LoVo cells. However, LoVo cells were found to be
      highly permissive for productive infection with a high viral titre (>3 x 10(7)
      viral copies/ml) produced in culture supernatant following a few days of
      incubation. SARS-CoV established a stable persistent chronic infection that could
      be maintained after multiple passages. Being a cell line of human origin, LoVo
      cells could be a useful in vitro model for studying the biology and persistent
      infection of SARS-CoV. Our results on the expression of angiotensin-converting
      enzyme 2 (ACE2), a recently identified cellular receptor for SARS-CoV, in these
      cell lines indicated that it might not be the sole determinant for cells to be
      susceptible to SARS-CoV infection.

PMID- 15258962
TI  - HIV therapy after treatment interruption in patients with multiple failure and
      more than 200 CD4+ T lymphocyte count.
AB  - The aim of the study was to investigate the safety and efficacy of a salvage
      therapy initiated after interrupting treatment in patients with virological
      failure and more than 200 CD4(+) T lymphocyte count. In this prospective study,
      77 patients who received failing regimens had stopped completely all medication
      for 3 months before starting an optimised regimen consisting of 3-5 drugs.
      Patients were tested for HIV resistance before and after treatment interruption.
      Discontinuation of therapy for 3 months was associated with a median increase in
      HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L
      and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven
      percent of patients showed a shift from a drug resistant genotype to a wild-type
      genotype based on the major resistance mutations. Forty-seven percent of patients
      with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12
      months after treatment resumption whereas none of those without a genotype shift
      did so (P = 0.03). However, the genotypic shift was not associated with a
      sustained virological response by multivariate analysis. The use of a new
      therapeutic class of compound in the salvage regimen was the only predictor of
      the sustained virological response. Salvage therapy with 3-5 drugs after
      interrupting treatment for 3 months can be a safe and effective strategy provided
      the HIV disease is not too advanced. Randomised trials in this population are
      needed to assess the clinical benefit of this strategy.

PMID- 15258963
TI  - Resistance profiles observed in virological failures after 24 weeks of
      amprenavir/ritonavir containing regimen in protease inhibitor experienced
      patients.
AB  - Amprenavir (APV) is an HIV protease inhibitor (PI) used for the treatment of
      either naive or PI-experienced HIV-infected patients. Several genotypic
      resistance pathways in protease gene have been described to be associated to
      unboosted APV failure (I50V, V32I + I47V, I54L/M, or less commonly I84V, which
      may be accompanied by one ore more accessory mutations such as L10F, L33F,
      M46I/L). The aims of this study were to investigate the efficacy up to week 24 of
      an APV plus ritonavir containing regimen in PI experienced patients and to
      determine the genotypic resistance profiles emerging in patients failing to this
      therapy. Forty-nine, PI experienced but APV naive patients were treated with APV
      (600 mg bid) plus ritonavir (100 mg bid). By intent-to-treat analysis, the median
      decrease in viral load (VL) was -1.32 log10 (min +0.6; max -2.8) and -1.46 log10
      (min +0.5; max -2.8) 12 and 24 weeks after initiating APV plus ritonavir regimen,
      respectively. Twelve patients harboured a VL >200 copies/ml at week 24. Among
      these patients, the selection of mutations previously described with the use of
      APV as first PI (V32I, L33F, M46I/L, I50V, 54M/L, and I84V) was observed.
      However, in some cases, mutations classically described after the use of other
      PIs (V82F and L90M) were selected but always with APV-specific mutations. There
      was no relation between the resistance pathways selected with either APV or
      ritonavir plasma minimal concentration, but higher APV plasma minimal
      concentration were associated with a lower rate of resistance mutations
      selection.

PMID- 15258964
TI  - Evolution of genotypic and phenotypic resistance to Enfuvirtide in HIV-infected
      patients experiencing prolonged virologic failure.
AB  - Four heavily antiretroviral-experienced HIV-infected patients had significant
      plasma HIV-RNA reductions (>1 log) after beginning an Enfuvirtide (ENF)-based
      rescue regimen. However, all had viral rebound shortly thereafter, sustaining
      high levels of plasma viremia over 80 weeks. These patients developed rapidly
      genotypic and phenotypic resistance to ENF. Mutations within the HR1 env region
      were selected (N43D in three and G36V/D in one), resulting in high-level
      phenotypic resistance to ENF. Interestingly, two patients had a sustained CD4+ T
      cell increase and two maintained stable CD4+ T-cell counts despite virologic
      failure under ENF. The possible mechanisms involved in this response were
      examined. Changes in virus tropism from R5 to R5/X4 were observed in two
      patients, in parallel with increases in ENF phenotypic resistance. Low levels of
      T-cell activation, T-cell turnover, and cytotoxic T lymphocyte (CTL) activity
      were found in all four patients. An overall increase in the proportion of viruses
      released from cells of the macrophage lineage was observed. In summary, single
      mutations at the HR1 env region result in significant loss of susceptibility to
      ENF. Despite virologic failure, these patients may maintain elevated CD4+ counts
      through a reduction in their overall immune activation.

PMID- 15258965
TI  - Drug resistance mutations and newly recognized treatment-related substitutions in
      the HIV-1 protease gene: prevalence and associations with drug exposure and real
      or virtual phenotypic resistance to protease inhibitors in two clinical cohorts
      of antiretroviral experienced patients.
AB  - This study aimed at identifying HIV-1 protease amino acid changes associated with
      protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions
      were correlated with the number of experienced PIs, reaching statistical
      significance only for those at positions 3, 44, and 74. The correspondence
      multivariate model demonstrated that > or =3 experienced PIs and substitutions or
      mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross
      resistance, including resistance for lopinavir and amprenavir in this cohort of
      patients who were naive for these drugs.

PMID- 15258966
TI  - HBV and HCV prevalence and viraemia in HIV-positive and HIV-negative pregnant
      women in Abidjan, Cote d'Ivoire: the ANRS 1236 study.
AB  - A retrospective survey estimating the prevalence of hepatitis viruses B (HBV) and
      C (HCV) was conducted on samples taken in 1,002 African pregnant women (501
      diagnosed as HIV-1 positive and 501 HIV-1 negative) participating in a clinical
      trial program conducted in Abidjan, Cote d'Ivoire (West Africa). Hepatitis B
      markers studied were HBs antigen (HBsAg), and if positive, HBe antigen/anti-HBe
      antibodies and HBV DNA. Two third generation (G3) HCV enzyme immunoassays (EIAs)
      were used for primary HCV screening. All anti-HCV antibody-positive sera were
      assessed further with supplementary assays (one another G3 EIA, RIBA 3.0, and HCV
      RNA). HCV genotypes were also determined. HBsAg was found in a similar proportion
      among HIV-positive (45/499, 9.0%, 95% confidence interval [95% CI], 6.6-11.9) and
      HIV-negative (40/498, 8.0%, 95% CI, 5.8-10.8) women (P = 0.58). The diagnosis of
      chronic hepatitis B, based on HBV DNA positive results, was more frequent in HIV
      positive women (26.7%), compared to HIV-negative women (9.4%) (P = 0.06). In the
      case of hepatitis C infection, after supplementary testing allowing the
      elimination of frequent false-positive screening results, a prevalence rate of
      about 1% was found, both in HIV-positive (6/501, 1.2%, 95% CI, 0.44-2.59) and HIV
      negative (4/501, 0.8%, 95% CI, 0.22-2.03) women (P = 0.53). Of the 10 samples
      confirmed positive and assessed for HCV RNA, eight (80%) were viraemic and
      belonged to HCV genotypes 1 or 2. The relative high frequency of HIV/HBV
      coinfection in Cote d'Ivoire emphasises the need for monitoring the risk of
      hepatotoxicity by antiretroviral therapy in such patients. We propose an accurate
      and cost-efficient algorithm for HCV diagnosis in Africa.

PMID- 15258967
TI  - Genetic variability of hepatitis C virus in chronically infected patients with
      viral breakthrough during interferon-ribavirin therapy.
AB  - Little is known about hepatitis C virus (HCV) breakthrough during antiviral
      therapy, although it would help in understanding HCV resistance to current
      antiviral treatments. To analyse the implication of virological factors and the
      vigour of humoral immune responses in this phenomenon, we studied nine chronic
      hepatitis C patients with a viral breakthrough during IFN/ribavirin combination
      therapy, as well as five responders and five non-responders. The IRES and regions
      coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and
      the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and
      during breakthrough, and after treatment. The major variant sequence was obtained
      by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in
      all patients and sequencing after cloning in seven genotype 1b-infected patients.
      Humoral responses against HCV epitopes were also analysed. The major sequences of
      IRES, PePHD, and NS5B remained stable during treatment, regardless of the
      treatment response. However, the capsid protein and the regions flanking PePHD
      showed sequence variations in breakthrough patients, although no specific
      mutation was identified. The variable V3 region of NS5A, but not the PKR-binding
      domain and the ISDR, seemed to be associated with differences in response to
      treatment. The analysis of HCV quasispecies revealed no characteristic pattern
      during treatment in breakthrough patients, whose HCV genome profiles looked most
      similar to that of non-responders. The humoral response was similar between
      groups. In conclusion, viral breakthrough does not seem to be due to selection of
      resistant strains with signature mutations.

PMID- 15258968
TI  - Mutations of the interferon sensitivity-determining region (ISDR) correlate with
      the complexity of hypervariable region (HVR)-1 in the Japanese variant of
      hepatitis C virus (HCV) type 1b.
AB  - Hepatitis C virus (HCV) genotype 1b comprises mainly two subtypes in Japan, each
      named for its geographic prevalence (Japan-specific, J type; worldwide, W type).
      Because the newly identified subtypes have not been fully characterized, the
      present study directed this issue from virological viewpoints such as
      hypervariable region (HVR)-1 as well as interferon (IFN) sensitivity-determining
      region (ISDR). Fifty chronic hepatitis patients with HCV 1b (31 men and 19 women;
      mean age 50.5 years) were enrolled, and J/W type was determined according to
      envelope 1 (E1) sequence as described previously (23 J type and 27 W type).
      Correlations between age, number of HVR-1 clones, HVR-1 diversity, and ISDR
      mutations were analyzed in J and W type patients independently. In addition, the
      sequences of the three HCV regions obtained for the determination of the above
      genetic factors were studied phylogenetically. The number of HVR-1 clones was
      significantly higher for J type in comparison with W type (P = 0.044). In the J
      type-infected patients, the ISDR mutation number was correlated inversely with
      HVR-1 clone number (P = 0.0001, r = -0.734) and HVR-1 diversity (P = 0.0001, r = 
      0.722). However, this correlation was not observed in the W type patients. W type
      patients showed a significant correlation between age and HVR-1 clone number (P =
      0.015, r = 0.462). Phylogenetic study revealed that the nonstructural (NS) 5A
      sequence, which is obtained for ISDR type determination, can distinguish between
      J and W types. The inverse correlation in J type patients between ISDR mutations
      and HVR-1 complexity may explain the usefulness of the ISDR for prediction of IFN
      response only in Japanese patients. This suggests that the ISDR is not directly
      related to IFN responsiveness, but the degree of HVR-1 complexity may be more
      important.

PMID- 15258969
TI  - Hepatitis C virus among self declared non-injecting sexual partners of injecting
      drug users.
AB  - While much is known about hepatitis C virus (HCV) among injecting drug users
      (IDUs), there is scant information about the risk of HCV infection to non
      injecting sexual partners of injecting drug users; it is possible that such
      individuals may have a greater risk of acquiring HCV than any other group barring
      injecting drug users. This study examines the prevalence of HCV among a
      population of non-injecting sexual partners of injecting drug users. Unlinked
      anonymous testing for anti-HCV of residual sera stored following the named HIV
      testing of specimens originally from persons who had indicated to their attending
      clinicians that they were non-injecting sexual partners of injecting drug users.
      The prevalence of anti-HCV among the sexual partners was 4.1% (25/611) overall,
      6.4% (13/202) among heterosexual male and 3.0% (12/397) among the heterosexual
      female partners. None of the homosexual/bisexual partners were HCV antibody
      positive (0/12). Although we cannot be sure how non-injecting partners of
      injecting drug users acquire their HCV infection, having a relationship with
      someone who injects drugs may place an individual at appreciable risk of being
      infected; such individuals should consider being tested for HCV.

PMID- 15258970
TI  - Consumption of uncooked deer meat as a risk factor for hepatitis E virus
      infection: an age- and sex-matched case-control study.
AB  - It was reported previously food-borne transmission of hepatitis E virus (HEV) to
      humans from deer meat. The present study attempted to clarify whether eating
      uncooked deer meat is a major epidemiological risk factor for HEV infection in
      Kasai, a city in western Japan. In total, 45 volunteer subjects with experience
      of eating raw deer meat were enrolled. An equivalent number of people from the
      same area who had never eaten raw deer meat served as controls. The subjects and
      controls had comparable age and sex distributions. Serum anti-HEV IgG and anti
      hepatitis A virus (HAV) IgG levels were measured in all 90 volunteers. There was
      no significant difference in age, overseas travel history, or rate of anti-HAV
      antibody positivity between the subjects and controls. Eight (17.7%) of the
      subjects but only one (2.2%) of the controls had measurable serum anti-HEV IgG
      levels (P = 0.014). Anti-HAV prevalence did not differ between the anti-HEV
      positive and negative groups. The results suggest that eating uncooked deer meat
      is an epidemiological risk factor for HEV infection in the studied area. In
      countries such as Japan where deer meat is sometimes eaten raw, attention must be
      paid to this route of HEV infection.

PMID- 15258971
TI  - One-year survey of astrovirus infection in children with gastroenteritis in a
      large hospital in Hungary: occurrence and genetic analysis of astroviruses.
AB  - Human astroviruses (HAstV) are the causative agents of viral gastroenteritis
      mainly in children worldwide. This study investigated the epidemiology and
      genotype diversity of HAstVs detected in children admitted to hospital with
      gastroenteritis in Hungary. Stool samples were collected from children with
      diarrhea at the Municipal "Szent Laszlo" Hospital, Budapest, Hungary, between
      January 2002 and December 2002. Of 2,758 samples, 607 were negative for both
      rotaviruses and bacterial pathogens and were tested for astroviruses using a
      reverse transcriptase-polymerase chain reaction (RT-PCR) targeting the open
      reading frame (ORF2), capsid region. Astrovirus was detected in 10 samples (1.6%)
      by RT-PCR. Astrovirus infection was more frequent among children 49 to 60 months
      of age. Genotyping of positive samples was performed by type-specific RT-PCR and
      confirmed by sequence analysis. Phylogenetic analysis was performed using a 203
      nucleotide consensus length of the 3'-end of the capsid gene. Type-specific RT
      PCR and sequence analysis detected genotypes 1 (50%), 4 (30%), 3 (10%), and 8
      (10%) among the children admitted to hospital. Genotype 1 was the predominant
      genotype, but genotypes 3, 4, and 8 were also present indicating the importance
      of emerging genotype 8 infections. Two distinct genotype 4 variants were observed
      during this study. Sequence analysis confirmed type-specific RT-PCR results in
      the capsid region. This is the first comprehensive report on the occurrence of
      HAstV infections in Central/Eastern Europe.

PMID- 15258972
TI  - Assessment of CMV load in solid organ transplant recipients by pp65 antigenemia
      and real-time quantitative DNA PCR assay: correlation with pp67 RNA detection.
AB  - After bone marrow (BM) or solid-organ (SO) transplantation viremic
      Cytomegalovirus (CMV) infection is observed frequently. Quantitative assay of CMV
      in blood helps the management of this clinical condition. In the present report,
      83 samples from 39 solid organ recipients, three CMV assays were compared
      simultaneously for the first time: the Nuclisens CMV pp67 assay (nucleic acid
      sequence-based amplification, NASBA), an "in-house" quantitative real-time PCR
      assay (TaqMan) for CMV DNA, and pp65 antigenemia. The relation between CMV DNA
      and pp65 antigenemia, the quantitative assays, was evaluated on a larger group
      including 251 blood samples from 118 solid organ recipients. Real-time PCR
      provided the best results; > or =130 CMV DNA copies/2 x 10(5) peripheral blood
      leukocytes (PBLs) predicted > or =1 pp65 antigen positive (Ag+) cell/2 x 10(5)
      PBLs. By taking pp65 antigenemia as the "gold standard," the sensitivity of CMV
      DNA quantitation and of the pp67 RNA assay were 0.95 and 0.20, respectively,
      while the corresponding specificity values were 0.50 and 0.93. When real-time PCR
      was considered as the "gold standard," the sensitivity and specificity of the
      pp65 antigenemia were 0.65 and 0.91, respectively. Among the three tests
      examined, the sensitivity of the pp67 RNA assay was the lowest. On the other
      hand, the pp67 RNA assay was highly specific and effective in pinpointing high
      viremia patients. The present report, by providing predictive values for all
      three diagnostic profiles, DNA load, antigenemia, and pp67RNA, is a contribution
      for validation of real-time PCR as a new standard for quantitative assessment of
      CMV viremia in clinical settings.

PMID- 15258973
TI  - Cytomegalovirus antiviral resistance associated with treatment induced UL97
      (protein kinase) and UL54 (DNA polymerase) mutations.
AB  - HCMV-related illness due to infections with antiviral resistant virus was
      verified by phenotypic and genotypic assays in 17% (8/47) of high-risk
      immunocompromised Australian patients. Selective PCR-sequencing of UL97 (protein
      kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral
      sensitivity, identified the majority (6/8) of resistant strains through detection
      of mutations known to confer antiviral resistance. Additionally, eight UL54
      (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V)
      of unknown phenotype were identified in six specimens from patients with clinical
      evidence of antiviral resistant infections. One isolate was resistant to
      ganciclovir (GCV) and another resistant to PFA on phenotypic testing where
      mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of
      correlation between phenotype and genotype. Selective PCR-sequencing of UL97 (PK)
      and UL54 (DNApol) provided rapid and comprehensive results, but missed some
      resistance detected by phenotypic assays. A combination of phenotypic and
      genotypic assays is recommended for complete analysis of CMV antiviral
      resistance, as well as further definition of the clinical relationship between
      novel UL54 (DNApol) mutations and antiviral resistance.

PMID- 15258974
TI  - Molecular markers of clonality and identity in Epstein-Barr virus-associated B
      cell lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease may be
      polyclonal, oligoclonal, or monoclonal. The degree of tumor clonality reflects
      the disease pathogenesis and may have implications for disease diagnosis,
      prognosis, and treatment. In this study, specimens of EBV-associated B-cell
      lymphoproliferative disease obtained from immunocompromised hosts were analyzed
      for molecular markers of cellular and virologic clonality and virologic identity.
      Each tumor specimen was assessed for immunoglobulin gene JH region rearrangement,
      the structure of the EBV genome termini, and the EBV genotype(s) present using a
      new EBV genotyping assay based upon LMP-1 gene sequence variation. The results of
      the JH rearrangement and EBV termini assays were generally concordant in their
      assessment of tumor specimen clonality, and both assays contributed to
      establishing clonal identity between different tumor specimens. The EBV
      genotyping assay did not significantly contribute to the assessment of tumor
      clonality but did established clear virologic identity between different tumor
      specimens obtained from the same individual. In one individual, these three
      assays together characterized a multi-focal, monoclonal tumor that may have
      arisen through clonal selection after sequential infections with two different
      EBV genotypes. In summary, the JH rearrangement and EBV termini assays each
      provided different but complementary information on tumor clonality, while the
      EBV genotyping assay proved most useful for establishing virologic identity among
      tumors. Utilization of these three assays together may provide new insight into
      the pathogenesis of EBV-associated B-cell lymphoproliferative disease.

PMID- 15258975
TI  - Prevalence and distribution of HSV-1, VZV, and HHV-6 in human cranial nerve
      nuclei III, IV, VI, VII, and XII.
AB  - The etiology of idiopathic cranial nerve palsies often remains unresolved. It has
      been hypothesised that viral reactivation of herpesviruses in the corresponding
      nuclei in the brainstem is the cause. We investigated the distribution of herpes
      simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) in nuclei that are
      associated with peripheral sensory ganglia [oculomotor (nIII), facial (nVII)
      nuclei] and in nuclei that are not associated with peripheral sensory ganglia
      [trochlear (nIV), abducens (nVI), and hypoglossal (nXII) nuclei] of five human
      brainstems. Samples of the cranial nerve nuclei and adjacent control tissue were
      taken from histological sections after precise identification of every single
      nucleus and control tissue. DNA and RNA amplification methods were used to
      determine the prevalence and distribution of HSV-1 and VZV. The distribution of
      human herpes virus type 6 (HHV-6) was also determined and served as a control,
      since HHV-6 infection has never been associated with idiopathic cranial nerve
      palsies. HSV-1 was distributed at random in all cranial nerve nuclei and control
      tissue, whereas VZV DNA was not detected in any of the samples examined.
      Surprisingly, HHV-6 was present in almost all samples where HSV-1 was also
      present, however, the latency associated transcript (LAT) of HSV-1 was not found
      in any of the samples positive for HSV-1 DNA. The absence of LAT in the samples
      positive for HSV-1 and the distribution of HSV-1 and HHV-6 do not support the
      hypothesis that idiopathic cranial nerve palsies result from viral reactivation
      in the brainstem nuclei.

PMID- 15258976
TI  - Detection of high-risk human papillomavirus E6 and E7 oncogene transcripts in
      cervical scrapes by nested RT-polymerase chain reaction.
AB  - The oncogenic potential of the high-risk human papillomavirus (HPV) genotypes
      (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) depends on the
      expression of the two viral oncogenes E6 and E7. Thus, the detection of HPV E6/E7
      oncogene transcripts could serve as a factor in the evaluation of a risk of
      development of cervical intraepithelial neoplasia (CIN) and its progression to
      cervical cancer. A nested RT-PCR assay for the detection of E6/E7 oncogene
      transcripts of all known high-risk HPV genotypes was established. In the study
      described, 779 high-risk HPV-DNA-positive cervical scrapes exhibiting all grades
      of CIN, including non-dysplastic cervical mucosa (CIN 0), were examined. Spliced
      E6/E7 oncogene transcripts of all the high-risk HPVs were detected in numerous
      samples, with an overall detection rate of 47%. In 227 cases with agreement
      between the cytologic and histologic findings, the prevalence increased with
      lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%; CIN III, 84%. Multiple
      transcriptionally active high-risk HPVs were detected in 12% (33/279) of patients
      with multiple high-risk HPV infections. This work sets the stage for a
      prospective follow-up study currently being undertaken to evaluate the prognostic
      relevance of the detection of high-risk HPV E6/E7 oncogene transcripts for the
      persistence of a high risk HPV infection, and the possible evolution and further
      development of a CIN. Future applications of the assay described may include the
      monitoring of women in studies investigating antiviral treatment or vaccination.

PMID- 15258977
TI  - Analysis of human papillomavirus type-16 variants in Italian women with cervical
      intraepithelial neoplasia and cervical cancer.
AB  - Human papillomavirus type 16 (HPV-16) classes (E, AA, As, Af1, Af2) and their
      variants have different geographic distribution and different degrees of
      association with cervical lesions. This study was designed to examine HPV-16
      variants among Italian women and their prevalence in case patients (affected by
      invasive cervical carcinoma or cervical intraepithelial neoplasia grade 2-3 and
      cervical intraepithelial neoplasia grade 1), versus control subjects with normal
      cervical epithelium (controls). A total of 90 HPV-16 positive cervical samples
      from women of Italian Caucasian descent have been tested, including 36 invasive
      cervical carcinomas, 21 with cervical intraepithelial neoplasias grade 2-3, 17
      with cervical intraepithelial neoplasia grade 1 and 16 controls. HPV-16 was
      detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV
      16 classes and subclasses were identified by direct nucleotide sequencing of the
      region coding for the E6 and the E7 oncoproteins, the MY09/11-amplified highly
      conserved L1 region, and the long control region (LCR). Among the 90 HPV-16
      samples, nine viral variants have been identified belonging to the European (Ep
      T350 and E-G350) and non-European (AA and Af-1) branches. The E-G350 is the
      prevalent variant in all analyzed different disease stages being present in 55.5%
      of ICC, 52.4% of cervical intraepithelial neoplasias 2-3, 47.1% of cervical
      intraepithelial neoplasia grade 1, and 50.0% of control samples. The non-European
      variants AA and Af1, rarely detected in control samples, represent 33.3% of all
      HPV-16 infections in invasive cervical carcinoma (with a peak of 19.4% and 13.9%,
      respectively), showing a statistically significant increase in frequency in more
      advanced lesions (chi(2) trend = 7.2; P < 0.05). The prevalence of HPV-16 Ep
      T350, however, is higher in controls (43.7%) and in of cervical intraepithelial
      neoplasia grade 1 (41.2%) than in cervical intraepithelial neoplasia grade 2-3
      (28.6%) and in invasive cervical carcinoma (11.1%) cases strongly suggesting lack
      of progression for pre-neoplastic lesions associated with such variant. The
      increased frequency of non-European variants in invasive lesions suggests that
      they are more oncogenic than European variants. This could have implications for
      future diagnostic and therapeutic strategies.

PMID- 15258978
TI  - New point of care test is highly specific but less sensitive for influenza virus
      A and B in children and adults.
AB  - The importance of rapid diagnosis of influenza has increased with the
      availability of neuraminidase inhibitors, which need to be commenced within 48 hr
      of symptom onset. Furthermore, the recent development of influenza-like clinical
      syndromes with novel aetiologies (severe acute respiratory syndrome, SARS) has
      increased the need for rapid and accurate near-patient diagnosis. A new, modified
      point of care (POC) diagnostic test (ZstatFlu) was assessed on 469 nasopharyngeal
      aspirates (NPAs) and 260 nose/throat swabs (TS) taken from children and adults.
      The test was specific (77-98%) for all specimen types for influenza virus A and
      B, depending upon incubation conditions. However, it was less sensitive,
      detecting 65-77% of specimens confirmed as positive on culture, direct
      immunofluorescence or PCR testing. A positive test is useful, for both directing
      initiation of therapy in the clinician's office, and making a positive diagnosis
      of influenza in patients with influenza-like clinical syndromes.

PMID- 15258980
TI  - Antigenic characterisation of influenza B virus with a new microneutralisation
      assay: comparison to haemagglutination and sequence analysis.
AB  - Although the haemagglutination inhibition assay is considered the "gold standard"
      for antigenic characterisation of influenza viruses, some limitations of this
      technique are well known. A new microneutralisation assay, as a tool for
      antigenic characterisation of influenza B viruses, has been standardised and its
      performance evaluated in comparison with the haemagglutination inhibition test in
      the light of molecular characterisation of the haemagglutinin. Twelve B viruses
      belonging to the two lineages and the four sub-lineages discriminated by
      phylogenetic analysis of HA were tested. The microneutralisation assay clearly
      distinguishes viruses belonging to different lineages and, in addition,
      discriminates strains belonging to different sub-lineages that are poorly or not
      discriminated using the haemagglutination inhibition test. This new
      microneutralisation assay could provide a useful tool for antigenic
      characterisation of circulating influenza viruses and contribute, together with
      the haemagglutination inhibition test and sequence analysis of the haemagglutinin
      and neuraminidase, in the choice of the strain for use in vaccine composition.

PMID- 15258979
TI  - Genetic diversity of influenza B virus: the frequent reassortment and
      cocirculation of the genetically distinct reassortant viruses in a community.
AB  - To characterize the genetic diversity of influenza B viruses isolated during one
      influenza season, the antigenic and genetic relationships among 20 strains of
      influenza B virus isolated in February and March 2001 at one pediatric clinic in
      Yamagata City, Japan, were investigated. The HA gene and seven other gene
      segments were phylogenetically divided into three distinct sublineages
      (Harbin/7/94-, Tokyo/6/98-, and Shiga/T30/98-related lineage) of the
      Yamagata/16/88-like lineage. The NS genes of the viruses belonging to the
      Harbin/7/94-related lineage have additional three nucleotides at positions 439
      447, and were phylogenetically distinguishable from those of the currently
      circulating Yamagata/16/88- and Victoria/2/87-like lineages, but were closely
      related to that of the Yamagata/16/88-like lineage isolated before 1994.
      Moreover, four strains of influenza B virus isolated in the same community
      between 2002 and 2003 were further examined. Phylogenetic analysis revealed that
      a virus of Victoria/2/87-like lineage isolated in 2003 had acquired the NA, NS,
      M, and PA gene segments from a Shiga/T30/98-like virus, and two strains of
      Harbin/7/94-related lineage had acquired the various gene segments from
      Shiga/T30/98-like virus through a reassortment event. These results indicate that
      genetically distinct multiple viruses can combine to cause an influenza B
      epidemic in a community and that the frequent reassortment among these viruses
      plays a role in generating the genetic diversity of influenza B viruses.

PMID- 15258981
TI  - Circulating cytokines and chemokines in acute symptomatic parvovirus B19
      infection: negative association between levels of pro-inflammatory cytokines and
      development of B19-associated arthritis.
AB  - The aim of the study was to characterise the profile and clinical correlates
      (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in
      symptomatic acute parvovirus B19 infection. Serum was examined from cases of
      acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and
      in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA),
      rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of
      cytokines/chemokines was measured in duplicate using the Bioplex Protein Array
      system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1
      beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1),
      granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth
      factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic
      infection was characterised by specific IgG positivity (83%), serum B19 DNA
      positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma,
      MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis
      were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients
      without arthritis, while those with rash had lower levels of TGF-beta 1. It is
      concluded that cytokine levels following acute symptomatic infection with
      parvovirus B19 indicate a state of immune activation. The profile of circulating
      mediators may provide insights into the possible pathogenesis of particular
      clinical manifestations of this infection.

PMID- 15258982
TI  - Genetic diversity of respiratory syncytial virus isolated during an epidemic
      period from children of northeastern Brazil.
AB  - Outbreaks of human respiratory syncytial virus (HRSV) are the leading cause of
      serious acute lower respiratory viral disease in many countries in different
      continents. Data on clinical and epidemiological aspects of HRSV infections in
      this country have been reported, but there is lack of data regarding the
      molecular epidemiology of this virus in Salvador. The genetic variability of HRSV
      isolated during an outbreak in Salvador, Brazil (1999) has been analysed. Partial
      sequences of the G protein gene of 13 isolates from antigenic group A and 4
      isolates from antigenic group B of HRSV were determined. Nucleotide sequences of
      C-terminal G gene were compared to sequences of HRSV isolates from countries of
      South America and from the rest of the world available at the GenBank. Brazilian
      group A and B isolates were clustered into previously characterised genotypes:
      GA5, GA2, GA7, and GB3, SAB3, respectively. This is the first study of GA7 and
      SAB3 genotypes circulation in South American countries. It is interesting to
      point out that viruses isolated in Salvador appear to be closer related with
      those from Montevideo-Uruguay and Buenos Aires, Argentina strains, suggesting
      circulation of similar strains among different South American countries in
      different seasons. Moreover, viruses closely related genetically circulated in
      the same year in Salvador and distant places such as Mozambique, supporting the
      previous suggestion on the complexity of HRSV strain circulation patterns, and
      the high capability of HRSV spreading world-wide.

PMID- 15258983
TI  - Nosocomial outbreak of respiratory syncytial virus subgroup B variants with the
      60 nucleotides-duplicated G protein gene.
AB  - In January 2001, 20 children among 40 residents under 2 years old at a nursery
      home in Sapporo, Japan had respiratory symptoms and were confirmed as having
      respiratory syncytial virus (RSV) infection by a conventional diagnostic kit.
      Nasopharyngeal aspirates were collected from four RSV-positive patients and total
      RNA was extracted directly from the specimens for the analysis of RSV grouping
      and genotyping. All four RSV strains had the same G protein gene sequence of
      subgroup B and were assigned to identical strains. Interestingly, the G protein
      gene had a duplication of 60 nucleotides at the C-terminal third of the G protein
      gene in which three nucleotides differed each other. The predicted polypeptide is
      lengthened by 20 amino acids. The clinical picture of these cases was not
      different from those of patients with other RSV strains. These novel mutations
      were thought to be introduced in vivo.

PMID- 15258984
TI  - Characterization of rotavirus strains from hospitalized and outpatient children
      with acute diarrhoea in Sao Paulo, Brazil.
AB  - From August 1994 to July 1995, 234 faecal samples from children with or without
      acute diarrhoea were collected and tested. The group of children with acute
      diarrhoea (A) was subdivided into two subgroups: subgroup A(1) was made up of
      children with severe diarrhoea, dehydrated and who needed hospitalization and
      subgroup A(2) was composed of children who only needed outpatient care. Group B
      was composed of children without acute diarrhoea (controls). Rotavirus was
      detected in 36.7% (18/49), 22.0% (15/68) and 1.7% (2/117) patients in groups
      A(1), A(2) and B, respectively. Of the 35 positive samples in which rotaviruses
      were detected the VP7 genotypes G1, G2, G3, G5 and the mixture (G2 + G5) were
      found in 40.0, 11.4, 11.4, 22.9 and 2.9% of the samples, respectively. Also, the
      VP4 genotypes P[8], P[4] and P[6] were detected in 57.1, 31.4 and 5.7%,
      respectively. Rotavirus VP6 subgroups I and II were detected at a frequency of
      22.4 and 54.3%, respectively. Rotavirus RNA segments had short and long
      electrophoresis profiles in 20.0 and 51.4% of the cases, respectively. The
      severity of the disease was not related to a specific G and P types, subgroup or
      electropherotype.

PMID- 15258985
TI  - Virus diversity and an outbreak of group C rotavirus among infants and children
      with diarrhea in Maizuru city, Japan during 2002-2003.
AB  - A total of 236 fecal specimens collected from infants and children with
      gastroenteritis in Maizuru city, Japan from July 2002 to June 2003, were tested
      for the presence of rotaviruses, noroviruses, sapoviruses, astroviruses, and
      adenoviruses by RT-PCR, PAGE, RPHA, and latex agglutination methods. Among
      diarrheal viruses detected, group A rotavirus was the most prevalent (32.2%; 76
      of 236) followed by norovirus GII (21.2%; 50 of 236), group C rotavirus (10.2%;
      24 of 236), adenovirus (3.8%; 9 of 236), sapovirus (2.5%; 6 of 236), astrovirus
      (1.3%; 3 of 236), and norovirus GI (0.8%; 2 of 236), respectively. It is
      noteworthy that group C rotavirus infection was apparently confined only within
      the period of 5 months (December 2002 through April 2003). This pattern of
      infection implied that the outbreak of group C rotavirus in these patients, which
      was the first outbreak of gastroenteritis attributed to group C rotavirus in
      Maizuru city. Moreover, about half (12 of 24) of group C rotavirus infected cases
      were confined to infants and young children less than 3 years old. Another
      interesting feature of the study was the demonstration of the mixed infections
      with group C rotavirus and group A rotavirus, as well as group C rotavirus and
      norovirus GII in 20.8% (5 of 24) and 8.3% (2 of 24), respectively. This is the
      first report of gastroenteritis associated with the mixed infections with group C
      rotavirus and other viral enteropathogens such as norovirus. The results indicate
      that group C rotavirus could infect not only older children and adults but also
      infants and young children under 3 years old.

PMID- 15258986
TI  - Differential expression of immunoregulatory genes in male and female Norway rats
      following infection with Seoul virus.
AB  - Males of many species are more susceptible than females to infections caused by
      parasites, bacteria, fungi, and viruses. Following inoculation with Seoul virus,
      male rats have more virus present in target organs and shed virus longer than
      females. The goal of this study was to test the hypothesis that variation in the
      expression of genes associated with immune function mediates sex differences in
      hantavirus infection. Using DNA microarrays, we examined changes in gene
      expression in lung tissue during the early (when animals are viremic and shedding
      virus; Day 15 post-inoculation (p.i.)) and late (animals have low levels of
      infectious virus, but high antibody titers; Day 40 p.i.) phases of infection in
      adult male and female rats. After normalizing the gene expression levels from
      infected animals to the gene expression levels from same-sex uninfected controls,
      our data revealed that 1,813 genes were differentially expressed between the
      sexes during infection. The expression of key transcriptional factors (e.g., eIF
      2 alpha, NF-kappa B, IRF-1, NF-IL-6, and STAT6) and genes that encode for
      proinflammatory (e.g., TNF alpha R, IL-1R, and IL-1RAcP), antiviral (e.g., IFN
      gamma R and Mx proteins), T cell (e.g., CD3 and TCR), and Ig superfamily (e.g.,
      IgM, IgG, and MHC class I and II) proteins was higher in females than males.
      Conversely, males had higher expression of heat shock protein genes (e.g., hsp70)
      suggesting that cellular stress is elevated in males. These data provide
      candidate genes and cellular pathways that may underlie sex differences in
      responses to Seoul virus and possibly other hemorrhagic fever viruses.

PMID- 15258987
TI  - Molecular and cellular basis of restenosis after percutaneous coronary
      intervention: the intertwining roles of platelets, leukocytes, and the
      coagulation-fibrinolysis system.
AB  - The major limitation of percutaneous coronary intervention (PCI) is restenosis.
      Restenosis is considered to be an overreaction of the natural healing process
      after traumatic balloon dilatation. An elaborate web of cellular and molecular
      responses, including the interaction of platelets, leukocytes, and the
      coagulation-fibrinolysis system, as well as the secretion of various growth
      factors and pro-inflammatory cytokines, contributes to neointimal hyperplasia and
      the development of restenosis. Moreover, platelet and neutrophil activation after
      stenting appears to be different from that after balloon angioplasty alone.
      Pharmacotherapy targeting the cell-to-cell interaction between platelets and
      neutrophils may potentially offer an effective treatment strategy against
      restenosis after PCI.

PMID- 15258988
TI  - Tissue pathology in undergraduate medical education: atrophy or evolution?
AB  - Changes are occurring in undergraduate medical curricula and there is limited
      published information about how contemporary tissue pathology is taught. The aim
      of this study was to collect information on this topic and to invite expert
      opinion about best teaching practice. A postal questionnaire survey of medical
      schools in the UK was performed, with a response rate of 23/28 schools (82%). The
      two most striking findings were the variation in teaching and learning strategies
      between schools and the spirit of the respondents, some relishing the challenges
      associated with reorganization and some thoroughly demoralized. The main concerns
      about pathology teaching were a feeling of lack of ownership of the content
      taught, an overall lack of visibility of tissue pathology in teaching and
      assessment, and staff shortages. Respondents valued the autopsy as an educational
      tool but were finding it increasingly difficult to provide. On the other hand,
      key opportunities for pathology teaching were highlighted through the
      questionnaire. The potential for developments in information technology and the
      possibility of creating national forums to develop core curricula and generate e
      resources was recognized. The findings of this study will provide a milestone
      against which future change in pathology education can be measured.

PMID- 15258989
TI  - Stress responses of PML nuclear domains are ablated by ataxin-1 and other
      nucleoprotein inclusions.
AB  - The polyglutamine diseases are characterized by expansion of triplet CAG repeats
      that encode polyglutamine tracts in otherwise unrelated proteins. One plausible
      explanation for the neurodegeneration of these disorders proposes that inclusions
      of such proteins sequester other significant nuclear proteins in inactive form.
      The present study shows that PML protein is sequestered by inclusions of the
      pathogenic mutant form of the polyglutamine protein ataxin-1 and that this
      sequestration removes from the nucleus the free 0.2-1 microm diameter PML nuclear
      domains (PML-NDs), together with at least one of their many cargo proteins
      (Sp100). The present study demonstrates that this sequestration can be effected
      equally by another nuclear protein, RED, which lacks a polyglutamine tract, but
      expresses a polar zipper repeat. The sequestered PML-NDs no longer respond to
      stress signals (heat shock or ionizing radiation) to which they are normally
      sensitive. In both cases, there is independent evidence that the cells initiate
      other responses to their injury (nuclear translocation of heat shock protein or
      generation of gamma-H2AX-rich nuclear foci, respectively). The data thus provide
      strong evidence that multiple species of nuclear inclusion functionally sequester
      PML-NDs. This mechanism is likely to distort cellular responses to injury of many
      different types.

PMID- 15258990
TI  - Genetic lineage of poorly differentiated gastric carcinoma with a tubular
      component analysed by comparative genomic hybridization.
AB  - Analysis of cell lineage is based on the use of genetic markers inherent to the
      lineage to be analysed. The breakpoints of unbalanced translocations, and the
      pattern of chromosomal loss/gain determined by comparative genomic hybridization
      (CGH), have been previously used to demonstrate lineages in diffuse-type gastric
      carcinoma. Signet ring cell carcinoma was shown to progress to poorly
      differentiated adenocarcinoma, and early diffuse-type gastric carcinoma to
      advanced diffuse-type gastric carcinoma. The present study focuses on poorly
      differentiated adenocarcinoma with a tubular component to clarify its derivation.
      CGH and array CGH were applied to DNA extracted from multiple portions of
      individual tumours and amplified by degenerate oligonucleotide-primed (DOP) PCR
      and the changes common to the samples in each tumour (stemline changes) were
      compared between the tumours with and those without a tubular component. Within
      individual tumours, the samples from the tubular component and those from the
      other components had common stemline changes and a very similar frequency pattern
      of chromosomal changes, indicating their common derivation. Frequent stemline
      changes were 8q+, 7p+, 3q+, 20q+, and 10p+, and these were different from those
      in the tumours without a tubular component. It was noticed that there were two
      subgroups in the tumours with a tubular component: one with 5p+, 6p+, 7p+, and
      10p+, and the other without these changes. The latter had cytogenetic and
      clinicopathological features similar to those of the tumours without a tubular
      component. Analysis of the clonal evolution process by constructing dendrograms
      for each tumour gave results consistent with the notion that the latter subgroup
      may derive from signet ring cell carcinoma and the former from tubular
      adenocarcinoma.

PMID- 15258991
TI  - Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma in an animal
      model of 'Helicobacter heilmannii' infection.
AB  - While Helicobacter pylori is accepted as the dominant human gastric bacterial
      pathogen, a small percentage of human infections have been associated with
      another organism, commonly referred to as 'Helicobacter heilmannii', which is
      more prevalent in a range of animal species. This latter bacterium has been seen
      in association with the full spectrum of human gastric diseases including
      gastritis, peptic ulceration, and gastric carcinomas, including gastric B-cell
      mucosa-associated lymphoid tissue (MALT) lymphoma. This study describes an
      analysis of the pathogenic potential of a number of 'H heilmannii' isolates in an
      animal model of gastric MALT lymphoma. BALB/c mice were infected with ten
      different 'H heilmannii' isolates originating from both human and animal hosts.
      The animals were examined at various time points for up to 28 months after
      infection. The infected animals initially developed a chronic inflammatory
      response within 6 months. This histological response increased in severity with
      the length of infection, with the development of overt lymphoma in some animals
      18 months after infection. MALT lymphomas were detected in up to 25% of the
      infected animals. The prevalence of lymphoma was dependent on the length of
      infection and the origin of the infecting isolates. A range of other histological
      features accompanied the lymphocytic infiltration, including invaginations of the
      gastric epithelium and associated hyperplastic tissue, mucus metaplasia, and a
      small number of diffuse large B-cell lymphomas. The ability to manipulate
      experientially the presence of the bacterium in the animal model will allow
      further studies examining the role of antigen drive in the development of
      Helicobacter-associated MALT lymphoma.

PMID- 15258992
TI  - Evidence for acid-induced loss of Cdx2 expression in duodenal gastric metaplasia.
AB  - Gastric metaplasia in the duodenum (GMD) is characterized by transdifferentiation
      of intestinal epithelial cells into gastric foveolar cells within the duodenal
      mucosa. GMD is often associated with duodenal ulceration. Higher duodenal acidity
      due to increased gastric acid output into the duodenum has been implicated in the
      development of GMD. Intestinal development and homeostasis are controlled by the
      homeobox transcription factor Cdx2, which is considered to be the master
      regulator of intestinal differentiation. Using immunohistochemistry, the present
      study shows that GMD is associated with loss of expression of Cdx2 and its target
      gene product sucrase-isomaltase. Quantitative RT-PCR experiments using the
      intestinal cell line Caco2 revealed that Cdx2 and sucrase-isomaltase were down
      regulated and gastric mucins MUC5AC and MUC6 were up-regulated under acidic
      culture conditions. Thus, it is suggested that increased acid exposure leads to
      GMD by impairing the transcription of Cdx2 and subsequently that of its intestine
      specific target genes.

PMID- 15258994
TI  - Change of HER-2/neu status in a subset of distant metastases from breast
      carcinomas.
AB  - It is assumed that HER-2/neu status remains consistent in breast carcinoma during
      metastatic spread, but in most previous studies primary tumours were compared
      with concurrent regional lymph node metastases. The present study investigated 31
      breast carcinomas and their corresponding lymph node and distant metastases for
      HER-2/neu status by immunohistochemistry (HercepTest) and fluorescence in situ
      hybridization (FISH) (PathVysion). In 14 cases, serum HER-2/neu (SHER-2) was
      measured sequentially using the Bayer Immuno 1 HER-2/neu assay. Comparing HER
      2/neu immunohistochemistry of primary tumours and distant metastases case by
      case, increased HER-2/neu expression was found in the distant metastases in 15
      cases (48.4%), three (9.7%) of which showed an increase from score 0 to score 3+.
      In contrast, lymph node metastases showed the same HER-2/neu expression as the
      primary tumours, confirmed by FISH. Two cases, which showed HER-2/neu score 3+
      and HER-2/neu amplification in the primary tumours, revealed increased SHER-2
      levels above 50 ng/ml at the first measurement. Five of the 14 cases (36%) showed
      an increase of SHER-2 above 50 ng/ml towards the end of the patients' life. On
      the basis of these results, there is evidence that in a subset of breast
      carcinomas, HER-2/neu amplification and overexpression occur de novo in distant
      metastases at a late disease stage.

PMID- 15258993
TI  - Expression of Sonic hedgehog pathway genes is altered in colonic neoplasia.
AB  - The Hedgehog (Hh) signalling pathway is crucial for normal development and
      patterning of numerous human organs including the gut. Hh proteins are also
      expressed during gastric gland development and gastric epithelial differentiation
      in adults. Recently, dysregulation of these developmentally important genes has
      been implicated in cancer, leading to the present study of the expression of Hh
      signalling proteins in colon cancer. In this study, normal colon and colonic
      lesions (hyperplastic polyp, adenoma, and colonic adenocarcinoma) were examined
      by immunohistochemistry using antibodies against Hh signalling molecules: the
      secreted protein Sonic hedgehog (SHH), its receptor Patched (PTCH), and the PTCH
      associated transmembrane protein Smoothened (SMOH). The study shows that Hh
      signalling pathway members are expressed in normal colonic epithelium. SHH was
      expressed at the top of the crypts and in a few basally located cells, while PTCH
      was detected in the neuroendocrine cells and SMOH at the brush border of
      superficial epithelium. RT-PCR analysis of laser-microdissected crypts from
      normal human colon confirmed that mRNAs encoding these proteins were expressed in
      colonic epithelium. Expression of SHH, PTCH, and SMOH was up-regulated in
      hyperplastic polyps, adenomas, and adenocarcinomas of the colon, and SHH
      expression correlated with increased expression of the proliferation marker Ki-67
      in all lesions examined. To address whether the Hh signalling pathway is
      functional in the gut, the effect of Shh on epithelial cells in vitro was
      explored by treating primary murine colonocytes with either Shh peptide or
      neutralizing anti-Shh antibody. The proportion of cells in the S-phase was
      assessed by bromodeoxyuridine (BrdU) incorporation. It was found that exogenous
      Shh promotes cell proliferation in colonocytes, while anti-Shh inhibits
      proliferation, suggesting that Shh is required during proliferation of epithelial
      cells in vitro. It is suggested that SHH is required during epithelial
      proliferation in the colon and that there is a possible role for Hh signalling in
      epithelial colon tumour progression in vivo.

PMID- 15258995
TI  - Metastatic dissemination of human malignant oral keratinocyte cell lines
      following orthotopic transplantation reflects response to TGF-beta 1.
AB  - This study examined the behaviour of nine human malignant oral keratinocyte cell
      lines following orthotopic transplantation to the floor of the mouth of athymic
      mice. Tumourigenesis, local spread, and metastatic dissemination were correlated
      with known cellular responses to transforming growth factor-beta 1 (TGF-beta 1).
      Six of nine cell lines were tumourigenic; four of these cell lines showed local
      spread which was characterized by vascular and bone invasion. Metastatic spread
      was uncommon, with only 9% of animals with primary tumours developing metastases
      and these were almost exclusively found in the regional lymph nodes; there was
      one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not
      reflect the clinical stage of the original tumours. Cell lines that were
      resistant to TGF-beta 1-induced growth inhibition were more likely to form
      primary tumours, exhibit local spread, and metastasize than cells that were
      growth-inhibited by the ligand. The data demonstrate that tumourigenicity and
      tumour behaviour in this orthotopic mouse model varied between cell lines and
      that the pattern of local invasion and metastasis was similar to that seen in
      human oral cancer. Furthermore, cell lines that were refractory to the growth
      inhibitory effects of TGF-beta 1 behaved more aggressively than cells that
      underwent ligand-induced cell-cycle arrest.

PMID- 15258996
TI  - The developmentally regulated neural crest-associated glycotope HNK-1 predicts
      metastasis in cutaneous malignant melanoma.
AB  - Aberrant glycosylation is a common feature of metastatic sub-clones of malignant
      tumours and in uveal melanoma in particular, the HNK-1 glycotope has been
      positively correlated with poor prognosis. So far, no such correlation has been
      investigated in cutaneous melanoma. In order to do so, HNK-1 expression was
      evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated
      with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression
      was analysed in metastatic deposits (19 distant cutaneous metastases and six
      sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis
      revealed a positive association between HNK-1 expression and metastasis (p <
      0.005) and multivariate Cox regression analysis adjusted for the standard
      prognostic markers ulceration and vertical tumour thickness confirmed HNK-1
      expression as an independent prognostic marker. HNK-1 expression was preserved in
      42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were
      devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited
      HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant
      melanoma is an independent prognostic marker of metastasis. Differential HNK-1
      expression at the metastatic sites implies that its expression is modulated by
      the surrounding environment. As HNK-1 is also transiently expressed during
      migration of melanocyte precursor cells derived from the neural crest,
      recapitulation of this transient expression might occur during metastatic spread
      of cutaneous malignant melanoma.

PMID- 15258997
TI  - Homogeneous immunophenotype and paucity of secondary genomic aberrations are
      distinctive features of endemic but not of sporadic Burkitt's lymphoma and
      diffuse large B-cell lymphoma with MYC rearrangement.
AB  - The present study has compared immunohistological marker expression profiles and
      genomic imbalances in seven African endemic Burkitt's lymphomas (eBLs) with those
      in ten European B-cell lymphomas with MYC rearrangement as shown by fluorescence
      in situ hybridization (FISH) analysis. eBLs showed a typical histomorphology and
      a homogeneous immuno-profile: CD10+, CD38+, CD77+, bcl-2-, and IgM+. Epstein-Barr
      virus (EBV) DNA was present in all cases. On comparative genomic hybridization
      (CGH), only three out of six eBLs showed imbalances (median number of imbalances
      = 2), with gains on chromosome 17 in two eBLs. The European lymphomas were all
      highly proliferating, with a Ki-67 index of at least 90%, and included seven with
      morphology typical of sporadic Burkitt's lymphoma (sBL) and three immunoblastic
      diffuse large B-cell lymphomas with MYC rearrangement (MYCre+DLBCL). In contrast
      to eBL, the immuno-profiles of the European lymphomas were less homogeneous and
      inconsistent for CD10, CD38, CD77, IgM and bcl-2 expression. EBV DNA was not
      detected. In five of seven sBLs, CGH showed a higher number of imbalances (median
      = 6), with recurrent gains on chromosome 1q (3/7) and losses on 12q and 17p
      (2/7), whereas all three MYCre+DLBCLs had fewer imbalances (median = 4), with
      gains on 17q in two of three lymphomas. It is concluded that eBL has a
      homogeneous immunohistology and few secondary genomic aberrations, whereas MYC
      rearranged and highly proliferating European B-cell lymphomas are a heterogeneous
      group that includes sBL and a subgroup of diffuse large B-cell lymphomas.

PMID- 15258998
TI  - CDK9/CYCLIN T1 expression during normal lymphoid differentiation and malignant
      transformation.
AB  - CDK9 is a member of the CDC2-like family of kinases. Its cyclin partners are
      members of the CYCLIN T family (T1, T2a, and T2b) and CYCLIN K. The CDK9/CYCLIN
      T1 complex is very important in the differentiation programme of several cell
      types, controlling specific differentiation pathways. Limited data are available
      regarding the expression of CDK9/CYCLIN T1 in haematopoietic and lymphoid
      tissues. The aim of this study was to analyse the expression of the CDK9/CYCLIN
      T1 complex in lymphoid tissue, in order to assess its role in B- and T-cell
      differentiation and lymphomagenesis. CDK9/CYCLIN T1 expression was found by
      immunohistochemistry in precursor B and T cells. In peripheral lymphoid tissues,
      germinal centre cells and scattered B- and T-cell blasts in interfollicular areas
      expressed CDK9/CYCLIN T1, while mantle cells, plasma cells, and small resting T
      lymphocytes displayed no expression of either molecule. CDK9/CYCLIN T1 expression
      therefore appears to be related to particular stages of lymphoid
      differentiation/activation. CDK9 and CYCLIN T1 were highly expressed in lymphomas
      derived from precursor B and T cells, from germinal centre cells, such as
      follicular lymphomas, and from activated T cells (ie anaplastic large cell
      lymphomas). Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma also
      showed strong nuclear staining. Diffuse large B-cell, Burkitt's lymphomas, and
      peripheral T-cell lymphomas, among T-cell lymphoproliferative disorders, showed a
      wide range of values. No expression of CDK9 or CYCLIN T1 was detected in mantle
      cell and marginal zone lymphomas. However, at the mRNA level, an imbalance in the
      CDK9/CYCLIN T1 ratio was found in follicular lymphoma and diffuse large B-cell
      lymphomas with germinal centre phenotype, and in the cell lines of classical
      Hodgkin's lymphomas, Burkitt's lymphomas, and anaplastic large cell lymphoma, in
      comparison with reactive lymph nodes. These results suggest that the CDK9/CYCLIN
      T1 complex may affect the activation and differentiation programme of lymphoid
      cells. The molecular mechanism through which the CDK9/CYCLIN T1 complex is
      altered in malignant transformation needs to be elucidated.

PMID- 15258999
TI  - Lumican expression is associated with the formation of mesenchyme-like elements
      in salivary pleomorphic adenomas.
AB  - Pleomorphic adenomas are the most common salivary gland tumour. Although this
      tumour is considered to be of epithelial origin, it contains 'mesenchyme'-like
      elements histologically. Lumican is a keratan sulphate proteoglycan that belongs
      to the small leucine-rich repeat (LRR) proteoglycans and has been reported to be
      associated with cartilage formation. These findings suggest that lumican
      expression may be related to the chondroid component in pleomorphic adenomas. To
      investigate this hypothesis, the present study investigated the expression and
      localization of lumican in 20 normal human salivary glands and 35 pleomorphic
      adenomas. Firstly, immunohistochemistry for lumican was performed with pepsin
      pretreatment. In normal salivary glands, lumican was deposited in the periductal
      regions. In pleomorphic adenomas, it was predominantly deposited in the hyaline
      (100%) and fibrous areas (89.4%). In 16 tumours (66.7%), lumican was also
      deposited in the chondroid areas. Without pepsin pretreatment, lumican was
      identified in myoepithelial cells in myxoid areas, lacuna cells in chondroid
      areas, and in the cytoplasm of inner ductal cells. In situ hybridization revealed
      lumican mRNA expression mainly in the inner cells, the neoplastic myoepithelial
      cells, and the lacuna cells. These results suggest that lumican is associated
      with the formation of 'mesenchyme'-like structures in pleomorphic adenomas. In
      conclusion, normal salivary glands express lumican, which appears to be related
      to stromal maintenance, and pleomorphic adenomas express lumican mRNA and
      protein, which may play important roles in the formation of 'mesenchyme'-like
      areas in this type of tumour.

PMID- 15259000
TI  - Glycosylphosphatidylinositol-specific phospholipase D immunoreactivity is present
      in islet amyloid in type 2 diabetes.
AB  - Numerous apolipoproteins associate with amyloid plaques. A minor high-density
      lipoprotein-associated protein, glycosylphosphatidylinositol-specific
      phospholipase D (GPI-PLD), has recently been described by the authors and others.
      Since GPI-PLD is synthesized by, and secreted from, pancreatic islet beta cells,
      the present study examined the hypothesis that GPI-PLD associates with islet
      amyloid. GPI-PLD immunoreactivity was examined in pancreatic tissues from type 2
      diabetic and non-diabetic humans. GPI-PLD binding to heparan sulphate
      proteoglycan was determined in the absence or presence of heparan sulphate or
      heparin. Fibril formation from human islet amyloid polypeptide was determined in
      the absence or presence of GPI-PLD. In non-diabetics, GPI-PLD immunoreactivity
      was present and co-localized with insulin, as opposed to co-localizing with
      amyloid in diabetics. No immunoreactivity for apolipoprotein A-I was present in
      islet cells or islet amyloid. Heparan sulphate proteoglycan, which is commonly
      present in most amyloid, bound GPI-PLD in vitro. GPI-PLD inhibited the formation
      of amyloid fibrils from synthetic islet amyloid polypeptide in vitro. GPI-PLD is
      therefore present in islet amyloid and appears to derive from local production
      from islets. This localization likely derives from interaction between GPI-PLD
      and heparan sulphate proteoglycan. Since GPI-PLD also inhibited islet amyloid
      polypeptide fibril formation in vitro, it is concluded that GPI-PLD may play a
      role in islet amyloid formation in type 2 diabetes.

PMID- 15259001
TI  - Increased expression of matrix metalloproteinases in the murine zymosan-induced
      multiple organ dysfunction syndrome.
AB  - Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue
      damage in several inflammatory diseases. Since the multiple organ dysfunction
      syndrome (MODS) is thought to result from systemic inflammation, overactivation
      of MMPs could contribute to the organ damage observed. The expression and
      activity of several MMPs were studied in a murine model for MODS. Sixty mice were
      given an aseptic intraperitoneal injection of lipopolysaccharide, followed, after
      6 days, by zymosan. At days 2, 5, 8, 12, and 16 after the injection of zymosan,
      the liver, lungs, spleen, and kidneys were collected from groups of mice for
      either RNA extraction, gelatinase zymography and collagenase (MMP-1 and -13)
      assays (six mice per time point), or immunohistochemistry (three mice per time
      point). A group of nine mice did not receive zymosan and acted as controls. The
      expression of MMP-2 mRNA in zymosan-treated mice was strongly up-regulated in
      liver tissue only. For MMP-9, this was the case in all organs examined.
      Quantitative gelatin zymography demonstrated the near complete absence of any
      gelatinase activity in tissues from control mice. However, in the liver, lungs,
      and especially the spleen of zymosan-treated animals, significantly increased
      activity of proform and active MMP-2 and -9 was observed with time. Overall, MMP
      1 and -13 activities were very low in all samples from the liver and lungs. In
      the spleen, however, high levels of MMP-1 and -13 were observed in zymosan
      treated animals. Immunohistochemical staining for MMP-2 was detected in the liver
      and spleen, but not in lung and kidney tissue of zymosan-treated animals.
      Staining for MMP-9 could be detected in liver, lung, and spleen tissues of
      zymosan-treated mice. For both MMPs, staining appeared to be limited to
      phagocytes. In conclusion, the data suggest a role for MMPs, especially MMP-9, in
      the pathogenesis of MODS.

PMID- 15259003
TI  - Commentary: Sorting the wheat from the chaff: identifying demyelinating
      components of the myelin oligodendrocyte glycoprotein (MOG)-specific autoantibody
      repertoire.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is the only myelin protein known to
      initiate a demyelinating autoantibody response in EAE, an animal model for
      multiple sclerosis (MS). The pathophysiological significance of MOG-specific
      autoantibodies in MS is, however, controversial, as high titer antibody responses
      to MOG are also found in many patients with non-demyelinating neurological
      diseases. In this issue of the European Journal of Immunology, von Budingen et
      al. demonstrate that demyelination in a primate model of MOG-induced EAE is
      mediated by MOG-specific antibodies directed against discontinuous, rather than
      linear, MOG epitopes. This functional segregation of pathogenic vs. non
      pathogenic autoantibodies in terms of epitope specificity may be crucial to
      understand the relevance of MOG-specific responses in human disease. This
      commentary discusses these findings in the context of the structure and
      immunobiology of MOG, and their implications with respect to antibody-mediated
      demyelination in MS.

PMID- 15259004
TI  - Frontline: Epitope recognition on the myelin/oligodendrocyte glycoprotein
      differentially influences disease phenotype and antibody effector functions in
      autoimmune demyelination.
AB  - Preliminary observations of humoral immunity against the myelin oligodendrocyte
      glycoprotein (MOG) in experimental allergic encephalomyelitis (EAE) and human
      multiple sclerosis (MS) suggest that a subset of anti-MOG autoantibodies directed
      against conformational epitopes is of pathogenic predominance. Here, we provide
      proof that in marmoset EAE, autoantibodies reactive against conformational
      epitopes of MOG are not only responsible for aggravating demyelination, but also
      an essential factor for disease dissemination in space within the central nervous
      system, a hallmark for typical forms of human MS. In terms of effector
      mechanisms, IgG deposition and complement activation occur exclusively in
      association with presence of these conformational antibodies, while
      microglial/macrophage activation appears to be a common immunopathological
      finding regardless of the fine determinant specificity of anti-MOG antibodies.
      These findings highlight for the first time the complex heterogeneity of function
      and pathogenicity in the polyclonal anti-MOG antibody repertoire of outbred
      species. Because the linear and conformational antibody determinants of MOG are
      shared between marmosets and humans, these results are directly relevant to
      understanding effector mechanisms of organ damage in MS.

PMID- 15259005
TI  - Commentary: Regulated equilibrium between opposite signals: a general paradigm
      for T cell function?
AB  - The co-signaling receptors specific for the different members of the B7 molecular
      family are cell surface glycoproteins that are essential to modulate and tune the
      TCR-mediated activation of T lymphocytes. The common characteristic is that their
      function appears to be dependent on the engagement of TCR by antigenic peptides
      presented in the MHC context by antigen-presenting cells. Interestingly, co
      signaling molecules can be distinguished into costimulators and co-inhibitors,
      the prototype being represented by CD28 and CTLA-4, respectively. In the case of
      costimulators, the co-signals integrate the signal originated from the TCR
      resulting in optimal T cell activation (two-signal model). In the case of co
      inhibitors, the co-signals would moderate and/or switch off the Ag-dependent T
      cell activation, thus acting as negative regulators of immune responses. The
      growing number of novel co-signaling molecules has recently highlighted the need
      to integrate the two-signal model with the emerging data on the different co
      inhibitory interactions. Thus, a model has been proposed based on the idea that
      the TCR signal alone cannot take a full decision on the nature of the functional
      outcome following an antigen-specific stimulation and that this final event is
      governed by the co-signaling molecules.

PMID- 15259006
TI  - Frontline: Characterization of BT3 molecules belonging to the B7 family expressed
      on immune cells.
AB  - New members of the B7 family have been recently described as regulators of T cell
      activation and function. Butyrophilin (BT) has also been related to the B7 family
      by sequence similarity analyses. We present a new subfamily called BT3, which
      belongs to the B7/BT family. The BT3 subfamily comprises three members (BT3.1,.2
      and.3) that exhibit 95% identity and form a monophylogenetic group along with the
      BT-related members. High expression levels of BT3 transcripts were detected in
      lymphoid tissues (mainly spleen, lymph node and PBL). Using anti-BT3 mAb we could
      demonstrate BT3 expression on immune cells including T, B and NK cells, monocytes
      and dendritic cells as well as hematopoietic precursors and some tumor cell
      lines. As described earlier for PDL-1 and ICOS-L, BT3 molecules are expressed on
      endothelial cells and up-regulated upon activation by IFN-gamma or TNF-alpha. The
      BT3.1 counter-receptor (BT3.1-R) was analyzed by means of binding experiments
      using BT3.1-Ig soluble protein. The BT3.1-R is not CD28, CTLA-4, ICOS, PD-1 or
      BTLA and seems restricted to some T cell and hematopoietic cell lines.
      Altogether, these data describe new members of the B7/BT family that may play a
      role in regulation of the immune response.

PMID- 15259007
TI  - Disruption of the stratum corneum allows potent epicutaneous immunization with
      protein antigens resulting in a dominant systemic Th2 response.
AB  - The skin is an important immunological organ with an outer protective layer, the
      stratum corneum forming a barrier between the skin-associated lymphoid tissue and
      the environment. We show that gently removing the stratum corneum with adhesive
      tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion
      by T cells from draining lymph nodes and high levels of specific IgE and IgG1
      with no IgG2a showed that the immune responses induced following epicutaneous
      antigen exposure are strongly Th2 biased. Similar responses were obtained with
      different antigens and mouse strains. In contrast, subcutaneous immunization with
      antigen delivery into the dermis was less potent and gave predominantly Th1
      responses. Removal of the stratum corneum increased expression of MHC class II,
      CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to
      migrate. Rapid migration from epidermis to draining lymph node was obtained,
      however, by exposure to antigen after removal of the stratum corneum, suggesting
      that maturation and migration of Langerhans cells are independently regulated
      events. These results suggest that antigen presentation by Langerhans cells gives
      predominantly Th2 responses. This may provide an explanation for allergic
      sensitization to some antigens. It may also be a useful non-invasive, non
      adjuvant-dependent method of vaccination.

PMID- 15259008
TI  - Diverse populations of T cells with NK cell receptors accumulate in the human
      intestine in health and in colorectal cancer.
AB  - T cells expressing NK cell receptors (NKR) display rapid MHC-unrestricted
      cytotoxicity and potent cytokine secretion and are thought to play roles in
      immunity against tumors. We have quantified and characterized NKR+ T cells
      freshly isolated from epithelial and lamina propria layers of duodenum and colon
      from 16 individuals with no evidence of gastrointestinal disease and from tumor
      and uninvolved tissue from 19 patients with colorectal cancer. NKR+ T cell
      subpopulations were differentially distributed in different intestinal
      compartments, and CD161+ T cells accounted for over one half of T cells at all
      locations tested. Most intestinal CD161+ T cells expressed alpha beta TCR and
      either CD4 or CD8. Significant proportions expressed HLA-DR,CD69 and Fas ligand.
      Upon stimulation in vitro, CD161+ T cells produced IFN-gamma and TNF-alpha but
      not IL-4. NKT cells expressing the Valpha24Vbeta11 TCR, which recognizes
      CD1d,were virtually absent from the intestine, but colonic cells produced IFN
      gamma in response to the NKT cell agonist ligand alpha-galactosylceramide. NKR+ T
      cells were not expanded in colonic tumors compared to adjacent uninvolved tissue.
      The predominance, heterogeneity and differential distribution of NKR+ T cells at
      different intestinal locations suggests that they are central to intestinal
      immunity.

PMID- 15259009
TI  - Reactive oxygen species induced by the deletion of peroxiredoxin II (PrxII)
      increases the number of thymocytes resulting in the enlargement of PrxII-null
      thymus.
AB  - In the thymus, CD4+ or CD8+ single-positive (SP) thymocytes develop and mature by
      positive and negative selection or undergo "death by neglect". CD4+ or CD8+ SP
      then circulate to other lymphoid tissues. We have investigated the role of
      reactive oxygen species (ROS) in thymocyte development using peroxiredoxin II
      (PrxII)-null mice. The level ofROS in PrxII-null thymocytes is higher than that
      in wild-type mice. Deletion of the PrxII gene leads to enlargement of the thymus
      in young (9 weeks) and old (64 weeks) mice. The increased number ofthymocytes in
      PrxII-null thymus is related to reduced hypodiploid cell formation. For mice on a
      normal diet, the ratio of SP to double-positive (DP) thymocytes in thymus of
      PrxII-null mice is lower than that in wild-type mice. After food restriction,
      which leads to increased ROS production, this ratio becomes much higher in PrxII
      null thymus. The amount of apoptosis, induced by food restriction orby the
      injection of dexamethasone, is consistently lower in PrxII-null thymocytes than
      in wild-type thymocytes. In the presence of low serum concentrations, PrxII
      deleted T cells proliferate more vigorously after stimulation with concanavalin
      A. Phytohemagglutinin- or OKT3-stimulated proliferation of human peripheral blood
      mononuclear cells is also higher in the presence of lower serum concentrations.
      Collectively, the results suggest for the first time that thymocyte maturations
      and proliferations are regulated by ROS levels induced by the deletion of PrxII
      gene in vivo.

PMID- 15259010
TI  - Essential role for platelet-activating factor-induced NF-kappaB activation in
      macrophage-derived angiogenesis.
AB  - Activated monocyte-macrophages have been implicated in tumor angiogenesis via
      their capacity to produce many potent angiogenic factors. However, the mechanisms
      leading to production of these angiogenic factors in macrophages remain to be
      elucidated. In this study, we demonstrated by use of a mouse Matrigel
      implantation model that mouse peritoneal macrophages induce angiogenesis. mRNA
      expression and protein synthesis of macrophage-derived crucial angiogenic factors
      such as IL-1, TNF-alpha, basic fibroblast growth factor, and vascular endothelial
      growth factor (VEGF) were blocked by platelet-activating factor (PAF) receptor
      antagonists. It was also observed that inhibitors of NF-kappaB blocked macrophage
      production of these angiogenic factors. Gene expression and protein synthesis of
      the angiogenic factors cited above were also inhibited in IkappaBalpha-mutated
      macrophages. VEGF is the most potent angiogenic factor in macrophage-induced
      angiogenesis. PAF antagonists or NF-kappaB inhibitors also inhibit the capacity
      of conditioned medium from LPS-stimulated human peripheral blood monocytes to
      induce sprouting of porcine pulmonary arterial endothelial cells. These data
      indicate that PAF-induced NF-kappaB activation is a common upstream pathway
      leading to the production of crucial macrophage-derived angiogenic factors. This
      will provide an important clue for a better understanding of mechanisms involved
      in tumor angiogenesis.

PMID- 15259011
TI  - Biological function of the soluble CEACAM1 protein and implications in TAP2
      deficient patients.
AB  - Interactions of natural killer (NK) cells with MHC class I proteins provide the
      main inhibitory signals controlling NK killing activity. It is therefore
      surprising to learn that TAP2-deficient patients suffer from autoimmune
      manifestations only occasionally in later stages of life. We have previously
      described that the CEACAM1-mediated inhibitory mechanism of NK cytotoxicity plays
      a major role in controlling NK autoreactivity in three newly identified TAP2
      deficient siblings. This novel mechanism probably compensates for the lack of MHC
      class I-mediated inhibition. The CEACAM1 protein can also be present in a soluble
      form and the biological function of the soluble form of CEACAM1 with regard to NK
      cells has not been investigated. Here we show that the homophilic CEACAM1
      interactions are abrogated in the presence of soluble CEACAM1 protein in a dose
      dependent manner. Importantly, the amounts of soluble CEACAM1 protein detected in
      sera derived from the TAP2-deficient patients were dramatically reduced as
      compared to healthy controls. This dramatic reduction does not depend on the
      membrane-bound metalloproteinase activity. Thus, the expression of CEACAM1 and
      the absence of soluble CEACAM1 observed in the TAP2-deficient patients
      practically maximize the inhibitory effect and probably help to minimize
      autoimmunity in these patients.

PMID- 15259012
TI  - Lack of dendritic cell maturation by the plant toxin ricin.
AB  - Several bacterial toxins either promote or inhibit the maturation of human
      monocyte-derived DC. Since the potent plant toxin ricin exploits the same cell
      entry pathway used by these bacterial toxins and shares identical catalytic
      activity with some of them, we have studied the capacity of ricin to induce DC
      maturation in vitro. Here, we show that in contrast to the bacterial proteins,
      ricin neither induces DC maturation nor interferes with LPS-induced DC
      maturation. There is no correlation between the absence of DC maturation and
      ricin dysfunction. Indeed, some of the ricin variants retain significant
      ribotoxicity and catalytic activity. We have extended these observations to
      ebulin-1, suggesting that this may be a general characteristic of plant-derived
      cytotoxic ribosome-inactivating toxins. The human immune system may therefore
      have evolved to recognize and rapidly respond to the bacterial proteins, whilst
      being less responsive to the equivalent plant cytotoxins. Understanding the
      effect of ricin on professional APC may provide insights into the generation of
      an anti-ricin vaccine and into the use of inactivated ricin A chains as delivery
      vectors as part of a vaccination protocol.

PMID- 15259013
TI  - Peritoneal and splenic B-1 cells are separable by phenotypic, functional, and
      transcriptomic characteristics.
AB  - B-1 cells constitute a distinct B cell population with unique phenotypic and
      functional characteristics. Although the origin of B-1 cells remains
      controversial, B-1 cells in different locations are generally considered to be
      part of the same pool. To determine the validity of this assumption, we examined
      peritoneal and splenic B-1 cells isolated by flow cytometric cell sorting from
      normal mice for several features. We found that splenic B-1 cells differ from
      peritoneal B-1 cells in terms of surface antigen expression, viability ex vivo,
      immunoglobulin secretion in vitro, stimulated cell cycle progression, and
      expression of Notch family, Notch-dependent, and Notch-associated genes. These
      results indicate that splenic and peritoneal B-1 cells are not the same and thus
      dispute the notion that B-1 cells are uniform, and may suggest that different
      subpopulations of B-1 cells arise separately, home individually, and/or are
      heavily influenced by local environmental factors.

PMID- 15259014
TI  - CD4-induced down-regulation of T cell adhesion to B cells is associated with
      localization of phosphatidyl inositol 3-kinase and LFA-1 in distinct membrane
      domains.
AB  - We have previously shown that binding of anti-CD4 antibody inhibit LFA-1
      dependent adhesion between CD4+ T cells and B cells in a p56(lck) and a PI3
      kinase-dependent manner. In this work, we investigated with two different T cell
      lines (Jurkat and A201) whether CD4 binding could alter interactions of the
      proteins putatively involved in this adhesion regulatory pathway. Anti-CD4
      binding was shown to induce a transient association between PI3-kinase and LFA-1,
      which took place in different regions of the plasma membrane. It was detected in
      detergent soluble membrane but also in detergent insoluble membrane consisting in
      raft microdomains, composed of GM1 and/or GM3 gangliosides. These results show
      that anti-CD4 Ab could modify the interaction between LFA-1 and signaling
      molecules, such as PI3-kinase and induce, in part, their recruitment in raft
      domains. By using specific inhibitors, raft integrity and CD4 association with
      GM3 were found necessary for observing the CD4-dependent inhibition of LFA-1
      mediated adhesion. These results strongly suggest that these molecular
      rearrangements in the membrane are necessary to induce down-regulation of LFA-1
      mediated adhesion.

PMID- 15259015
TI  - A conserved sequence in the mouse variable T cell receptor alpha recombination
      signal sequence 23-bp spacer can affect recombination.
AB  - Although the V-gene segments coding for the TCR alpha and delta chains are mixed
      together in the alpha delta locus and are recombined by the same processes, some
      gene segments (TRAV) are rearranged only with TCR Jalpha gene segments, some
      (TRDV) only with TCR Ddelta gene segments and some (TRADV) with both. To date, no
      molecular signal is known that can characterize these three different types of
      gene segments. Studying the recombination signal sequences (RSS) of all mouse TCR
      V-gene segments we observed that 80% of the TRAV contain a palindrome sequence
      (CTGCAG) or its related variant CTGTAG in their 23-bp spacer. Using gel-shift
      assays we show that these sequences are specifically recognized by some nuclear
      proteins that are expressed by fresh thymocytes, fresh lymphocytes and tumor
      cells. Recombination assays on plasmid substrates in a pre-B cell line showed
      that RSS containing the CTGCAG sequence can impair recombination. From the
      protein fractions containing the CTGCAG-binding activity, three proteins were
      identified: G3BP1 (a nucleic-acid-binding protein with a proposed helicase
      activity) and two proteins from the high-mobility group (HMG) family--HMGB2 and
      HMGB3. We hypothesize that these proteins can affect recombination at the TCR
      alpha delta locus.

PMID- 15259016
TI  - Knockdown of C-terminal Src kinase by siRNA-mediated RNA interference augments T
      cell receptor signaling in mature T cells.
AB  - C-terminal Src kinase (Csk) controls the Src family kinase Lck, which is
      essential for T cell antigen receptor (TCR)-mediated signaling. For the first
      time, we here report the effects of acute elimination of Csk in Jurkat T cells
      and primary T cells using short interfering (si) RNA. In both cell types, 70-85%
      knockdown of Csk was achieved within 48 h. No alterations in surface expression
      of CD3, CD4 or CD8, or in Lck protein level were observed. Phosphorylation of
      Y505 in Lck was markedly reduced and a concomitant 4-5-fold increase in Lck Y394
      phosphorylation was observed both in normal and Jurkat T cells. Kinase assays
      revealed 2-3-fold higher Lck activity. In Jurkat cells, basal levels of zeta
      chain phosphorylation were elevated, and spontaneous NFAT-AP-1 activation
      occurred, indicating aberrant Lck kinase activity. After TCR triggering, Csk
      knockdown cells revealed faster and stronger, but not sustained, phosphorylation
      of Lck Y394 and zeta chains compared to control. TCR-induced activation of NFAT
      AP-1 and TCR/CD28-stimulated IL-2 secretion occurred at weaker stimuli and with
      augmented responses in Csk knockdown Jurkat and primary T cells, respectively.
      Altogether, these data suggest that acute elimination of Csk in T cells without
      evolution of compensatory mechanisms results in aberrant Lck activity and
      augmented TCR-stimulated responses.

PMID- 15259017
TI  - Quantitative trait loci (QTL) analysis reveals a close linkage between the hinge
      region and trimeric IgA dominancy in a high IgA strain (HIGA) of ddY mice.
AB  - Polymerization of IgA has been suggested as one of the causes of mesangial
      deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy,
      established by selective mating of ddY mice. This strain is characterized by a
      unique profile of the IgA molecule that is dominantly polymeric and has high
      serum levels with intense IgA deposition on the mesangium. We carried out
      quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA
      with BALB/c mice. Significant linkage of polymeric IgA in serum samples was
      identified around D12Mit263, which is close to the gene of the immunoglobulin
      heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain
      revealed marked differences between BALB/c and HIGA mice. Furthermore, most
      differences were focussed on the hinge region. The DBA/2J strain, which has the
      same amino acid sequence in the hinge region as the HIGA strain, also showed
      polymeric IgA dominance but low IgA levels in sera. Size fraction analysis
      revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA
      mice. In conclusion, the hinge region plays a key role in trimeric IgA formation
      in HIGA mice.

PMID- 15259018
TI  - Signaling assemblies formed in mast cells activated via Fcepsilon receptor I
      dimers.
AB  - Although aggregation of the Fcepsilon receptor I (FcepsilonRI) is necessary for
      Ag-mediated mast cell triggering, the relationship between the extent of the
      FcepsilonRI aggregation and subsequent biochemical and topographical events is
      incompletely understood. In this study, we analyzed the activation events induced
      by FcepsilonRI dimers, elicited by binding of anti-FcepsilonRI mAb to rat
      basophilic leukemia cells. We found that, in contrast to extensively aggregated
      FcepsilonRI, receptor dimers (1) induced a less extensive association of
      FcepsilonRI with detergent-resistant membranes, (2) delayed the tyrosine
      phosphorylation and membrane recruitment of several signaling molecules, (3)
      triggered a slower but more sustained increase in concentration of free
      cytoplasmic calcium, (4) induced degranulation which was not inhibited at higher
      concentrations of the cross-linking mAb, and (5) failed to produce clusters of
      FcepsilonRI, Syk kinase and Grb2 adapter in osmiophilic membranes, as detected by
      immunogold electron microscopy on membrane sheets. Despite striking differences
      in the topography of FcepsilonRI dimers and multimers, biochemical differences
      were less pronounced. The combined data suggest that FcepsilonRI-activated mast
      cells propagate signals from small signaling domains formed around
      dimerized/oligomerized FcepsilonRI; formation of large FcepsilonRI aggregates in
      osmiophilic membranes seems to promote both strong receptor triggering and rapid
      termination of the signaling responses.

PMID- 15259019
TI  - Characterization of HLA-DR- and TCR-binding residues of an immunodominant and
      genetically permissive peptide of the 16-kDa protein of Mycobacterium
      tuberculosis.
AB  - The 16-kDa protein of Mycobacterium tuberculosis represents an important
      antigenic target during bacillary latency and, consequently, should be considered
      as candidate subunit vaccine component. In this study, we have used CD4 T cell
      clones that recognize the peptide p91-110, an immunodominant and genetically
      permissive epitope, in the context of five different HLA-DR molecules and
      truncated and substituted variants of this peptide, to identify the minimal
      binding sequence (HLA-DR-binding core) and the minimal stimulatory sequence (TCR
      binding core), as well as the residues that contact HLA-DR molecules and the TCR.
      We have found a common 9-mer sequence, spanning amino acids 93-101, as the
      binding core for HLA-DR1, -DR11, -DR13 and -DR7, but a longer (13-mer) sequence
      spanning amino acids 92-104 was required for binding to the HLA-DR15 molecules.
      F(93) was required for binding to all the tested HLA-DR molecules, hence allowing
      us to identify it as the N-terminal primary anchor residue (P1). Additionally,
      the binding requirements for other residues varied considerably between the
      tested alleles: A(94) for HLA-DR15, V(99) for HLA-DR1, -DR15, -DR11 and -DR7,
      R(100) for HLA-DR11 and -DR13, and L(104) for HLA-DR15. Concerning the residues
      of p91-110 peptide required for binding to the TCR, the pepscan analysis results
      would support the contention that P(-1) E(92), P6 F(98) would be important TCR
      contact sites because their substitutions led to full loss of T cell activation.
      Moreover, P8 R(100) is found to be critical residue in binding to HLA-DR11- and 
      DR13-restricted T cell clones, without influencing binding to the relevant HLA-DR
      molecule. Our results could be useful to design peptides with altered HLA anchor
      residues or TCR interaction sites to achieve remarkable increase in activity and
      to study their vaccine potential.

PMID- 15259020
TI  - Mice deficient in invariant-chain and MHC class II exhibit a normal mature B2
      cell compartment.
AB  - The role of the invariant chain (Ii), an MHC class II-associated chaperone, in B
      cell development is controversial. Ii deficient mice (Ii(-/-) mice) show a defect
      in B cell development. This defect has been attributed to the absence of a
      fragment liberated from the Ii by intramembranous proteolysis. It was proposed
      that this fragment is required for activation of the NF-kappaB pathway as a means
      of controlling B cell maturation. The opposing view holds that defects in the
      assembly of MHC class II molecules result in impaired B cell development. Here we
      demonstrate that a lack of Ii indeed causes defects in B cell development, with
      fewer mature B cells in the periphery as previously reported, but that in a
      compound-mutant from which both Ii and all MHC class II subunits are absent, B
      cell development is normal. We suggest that neither Ii itself, nor the MHC class
      II products are required for normal B cell development.

PMID- 15259021
TI  - PLCgamma2 regulates Bcl-2 levels and is required for survival rather than
      differentiation of marginal zone and follicular B cells.
AB  - B cells from phospholipase C (PLC)gamma2-deficient mice express reduced levels of
      the pro-survival protein Bcl-2 and show a defect in the development of
      transitional T3 and marginal zone (MZ) B cells that reflects reduced B cell
      survival. Introduction of a bcl-2 transgene restored the numbers of MZ, T3 and
      follicular B cells in PLCgamma2(-/-) mice. Restricting the B cell repertoire in
      PLCgamma2-deficient mice by the introduction of a BCR transgene resulted in a
      striking reduction in the number of IgM-positive B cells and a paucity of IgD
      expressing cells in the spleen which was also rescued by the bcl-2 transgene. BCR
      stimulated ERK and IkappaBalpha phosphorylation were PLCgamma2 dependent, while
      calcium flux was reduced, but not abrogated, in the absence of PLCgamma2,
      suggesting an ancillary role for PLCgamma1. The bcl-2 transgene rescued
      development of PLCgamma2(-/-) B cells and serum IgM levels but did not restore
      BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest
      that PLCgamma2 performs a critical role in B cell development through regulation
      of survival rather than differentiation.

PMID- 15259022
TI  - Gamma delta T cells inhibit in vitro growth of the asexual blood stages of
      Plasmodium falciparum by a granule exocytosis-dependent cytotoxic pathway that
      requires granulysin.
AB  - Several reports have stated the ability of gamma delta T cells to inhibit the
      growth of the asexual blood stages of Plasmodium falciparum in vitro. However,
      little information is available about the mechanisms involved. In this study, in
      vitro systems were used to study the role of the granule exocytosis-dependent
      cytotoxic pathway in the growth inhibition/killing of P. falciparum by human
      gamma delta T cells. Our results show that the inhibition requires cell-to-cell
      contact and that gamma delta T cells kill the asexual blood stages of P.
      falciparum through a granule exocytosis-dependent cytotoxic pathway after
      recognition of certain ligands or molecules expressed on the surface of infected
      erythrocytes or merozoites. The in vitro inhibitory capacity of gamma delta T
      cells was strongly correlated with the expression of granulysin in the cytotoxic
      granules, while non-inhibitory CD4+ and CD8+ T cells expressed very little,
      implicating a role for granulysin in parasite inhibition. This was further
      suggested by the addition of neutralizing anti-granulysin antibodies, which
      abrogated the parasite inhibitory capacity of the gamma delta T cells. Taken
      together, our results suggest that the capacity of gamma delta T cells for
      inhibition/killing of P. falciparum is based on the granule exocytosis-dependent
      cytotoxic pathway and that the presence of granulysin is essential to maintain
      efficient killing.

PMID- 15259023
TI  - Macrophage colony-stimulating factor-, granulocyte-macrophage colony-stimulating
      factor-, or IL-3-dependent survival of macrophages, but not proliferation,
      requires the expression of p21(Waf1) through the phosphatidylinositol 3
      kinase/Akt pathway.
AB  - Mouse bone marrow-derived macrophages proliferate in the presence of macrophage
      colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating
      factor, or IL-3, but undergo apoptosis in their absence. Inhibition of
      extracellular signal-regulated kinases (ERK)-1/2 blocks growth factor-dependent
      proliferation but not survival, indicating that the two processes require
      independent signaling pathways. Although M-CSF induces the activation of other
      kinase pathways, such as c-Jun N-terminal kinase, p38, and phosphatidylinositol 3
      kinase (PI-3K), these pathways are not required for proliferation. However, PI-3K
      is the only one necessary for the induction of survival, as demonstrated using
      the inhibitors LY294002 and Wortmannin. Growth factors also activate Akt kinase
      and a transient expression of the cdk inhibitor p21(Waf1), which inhibits
      apoptosis but is not required for proliferation. PI-3K inhibitors also block
      growth factor-dependent expression of p21(Waf1) and the activation of Akt.
      Moreover, the survival induced by cyclosporin A or decorin is also dependent on
      the PI-3K/Akt kinases and p21(Waf1). These findings demonstrate that the
      induction of p21(Waf1) through the PI-3K/Akt pathway is a general survival
      response of macrophages. Our results show that growth factors in macrophages use
      two pathways: one for proliferation, mediated by ERK, and the other for survival,
      which requires the PI-3K/Akt kinases and p21(Waf1).

PMID- 15259024
TI  - Functional expression of CD134 by neutrophils.
AB  - CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor superfamily
      expressed on activated T cells. Here, we show that human peripheral blood
      neutrophils express CD134. Activation of CD134 by soluble CD134 ligand (OX40
      ligand/gp34) resulted in delayed caspase-3 activation and consequently in delayed
      neutrophil apoptosis in vitro. Moreover, CD134 ligand, like G-CSF, maintained
      anti-apoptotic Mcl-1 levels and inhibited cleavage of the pro-apoptotic Bcl-2
      family members Bid and Bax in these cells, suggesting that CD134-mediated signals
      block apoptosis pathways proximal to mitochondria activation. In conclusion,
      CD134 regulates neutrophil survival, suggesting that this molecule does not only
      contribute to adaptive but also to innate immune responses.

PMID- 15259025
TI  - A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte
      endothelium interactions under shear stress.
AB  - Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule mediating
      leukocyte interactions with blood vessels during leukocyte extravasation.
      Molecularly VAP-1 is a cell-surface-expressed ecto-enzyme belonging to the group
      of semicarbazide-sensitive amine oxidases (SSAO; EC 2.4.6.3), which deaminate
      primary amines. Here we asked whether peptides displaying a suitable free amine
      group could be a substrate or inhibitor of SSAO and thus regulate VAP-1-mediated
      leukocyte adhesion. On the basis of a molecular model of VAP-1, we designed
      synthetic peptides that fit to the substrate channel of VAP-1. One of these
      lysine-containing peptides effectively inhibits VAP-1-dependent lymphocyte
      rolling and firm adhesion to primary endothelial cells under physiologically
      relevant shear conditions. The same peptide inhibits the SSAO activity of
      endothelial and recombinant VAP-1 in a selective and long-lasting manner. We also
      show that all enzymatically active VAP-1 is displayed on the cell surface. Our
      results suggest that, in addition to soluble amines, specific cell-surface-bound
      molecules containing free NH(2) groups in a suitable position may modulate the
      enzymatic activity of SSAO. Moreover, the inhibitory peptide diminishes leukocyte
      interactions with endothelial cells under conditions of shear, and thus it may be
      useful to treat inflammatory conditions.

PMID- 15259026
TI  - IL-8 induces a specific transcriptional profile in human neutrophils: synergism
      with LPS for IL-1 production.
AB  - IL-8 is an inflammatory CXC chemokine involved in neutrophil recruitment and
      activation in various inflammatory conditions. The transcriptional profile
      induced by IL-8 in human neutrophils was analyzed using high-density
      oligonucleotide arrays and compared with that of the prototypic phagocyte
      activator LPS. As expected, LPS induced a major effect on the cell transcriptome,
      upregulating 116 (0.93%) and downregulating 70 (0.56%) of the transcripts. IL-8
      induced a less profound modulation of the cell transcriptome, with upregulation
      of 30 (0.25%) and downregulation of 6 (0.04%) of the transcripts. Although the
      two proinflammatory mediators induced partially overlapping transcriptional
      profiles (50.0% of IL-8-responsive genes were concordantly regulated by LPS), IL
      8 also modulated a significant number of genes unresponsive to LPS, including
      soluble mediators, membrane receptors, signaling molecules, and regulators of
      transcription and translation. A set of IL-8-inducible genes was related to cell
      motility, possibly a strategy to prepare for migration into tissues. Analysis of
      the IL-8-responsive gene IL-1beta at the protein level revealed that transcript
      induction was not followed by protein production. Neutrophils stimulated with IL
      8, however, showed a significant increase in IL-1beta secretion after subsequent
      exposure to LPS. Thus, the effect of IL-8 at the transcriptional level could
      provide a synergistic effect with microbial products for neutrophil activation.

PMID- 15259027
TI  - Secretory phospholipase A2 induces dendritic cell maturation.
AB  - High level of phospholipase A(2) (PLA(2)) activity is found in serum and
      biological fluids during the acute-phase response (APR). Extracellular PLA(2) in
      fluids of patients with inflammatory diseases such as sepsis, acute pancreatitis
      or rheumatoid arthritis is also associated with propagation of inflammation.
      PLA(2) activity is involved in the release of both pro- and anti-inflammatory
      lipid mediators from phospholipids of cellular membranes or circulating
      lipoproteins. PLA(2) may thus generate signals that influence immune responses.
      Here, group III secretory PLA(2) were tested for their ability to promote
      generation of functionally mature human dendritic cells (DC). PLA(2) treatment of
      differentiating monocytes in the presence of granulocyte/macrophage colony
      stimulating factor and IL-4 yielded cells with phenotypical and functional
      characteristics of mature DC. This maturation was dependent on the dose of
      PLA(2), and PLA(2)-generated DC stimulated IFN-gamma secretion by allogeneic T
      cells. The effects of PLA(2) on DC maturation was mainly dependent on enzyme
      activity and correlated with the activation of NF-kappaB, AP-1 and NFAT. The data
      suggest that transient increase in PLA(2) activity generates signals that promote
      transition of innate to adaptive immunity during the APR.

PMID- 15259028
TI  - Pre-exposure to sub-saturating concentrations of HLA class I antibodies confers
      resistance to endothelial cells against antibody complement-mediated lysis by
      regulating Bad through the phosphatidylinositol 3-kinase/Akt pathway.
AB  - Allografts transplanted across HLA-sensitization results in an antibody-mediated
      rejection known as hyperacute rejection. Depleting anti-graft antibodies from the
      recipient by plasmapheresis prior to transplantation can prevent this rejection.
      We developed an in vitro model using polyclonal HLA class I antibodies obtained
      from highly sensitized patients awaiting transplantation,and analyzed their
      ability to provide signals following binding to human aortic endothelial cells
      (EC). Using this model, we show that EC undergo caspase 3-dependent cell death by
      apoptosis upon exposure to saturating concentrations of HLA class I antibodies
      and complement accompanied by loss of Akt activation and phosphorylation of Bad.
      In contrast, exposure of EC to sub-saturating concentrations of HLA class I
      antibodies conferred resistance towards antibody/complement-mediated lysis termed
      accommodation. Accommodated EC exhibited reduction in the expression of the
      adhesion molecules ICAM-1 and VCAM-1 and a significant increase in the expression
      of anti-apoptotic genes Bcl-xL, Bcl-2 and heme oxygenase-1. Further, induction of
      phosphatidylinositol 3-kinase (PI3K) and Akt activities that facilitate the
      phosphorylation of Bad were also noted. In conclusion, exposure of sub-saturating
      concentrations of HLA class I antibodies results in the induction of PI3K/Akt
      pathway that confers resistance to endothelial cells against antibody/complement
      mediated cell death.

PMID- 15259029
TI  - Significant NK cell activation associated with decreased cytolytic function in
      peripheral blood of HIV-1-infected patients.
AB  - One of the hallmarks of HIV-1 infection is represented by the finding of massive
      T cell activation in peripheral blood lymphocytes of infected patients. An
      impairment of NK cell function during HIV-1 infection is also detected, and is
      associated with decreased expression of natural cytotoxicity receptors (NCR). In
      this study we tried to determine whether also NK cells are affected by relevant
      activation and whether this could be associated with decreased NK cell function.
      In 18 viremic HIV-1-infected patients, freshly drawn purified peripheral NK cells
      displayed significant levels of activation with an incomplete pattern (HLA
      DR(+)CD69(+)CD25(-)NKp44(-)). Activated (HLA-DR(+)CD69(+)) peripheral NK cells
      expressed an NCR(dull) phenotype as determined by cytofluorometric analysis in
      all the patients, and did not derive from a homogeneous/oligoclonal expansion in
      vivo as analyzed by expression of HLA-specific inhibitory NK cell receptors. As
      determined by cytotoxicity assays, activated NK cells showed a decreased
      cytolytic function in HIV-1-infected patients. Thus, the decrease in NK cell
      function observed during HIV-1 infection is associated not only with decreased
      NCR expression, but also with significant and incomplete NK cell activation in
      vivo. These results suggest a consistent continuous involvement of the innate
      immune response in the failure to control viral replication.

PMID- 15259030
TI  - Regulatory gamma delta T cells in Heymann nephritis express an invariant
      Vgamma6/Vdelta1 with a canonical CDR3 sequence.
AB  - Gammadelta T cells are expanded in human IgA nephropathy and in a rat model of
      adriamycin (ADR)-induced nephropathy. Despite different diseases and species,
      these renal gammadelta T cells use a restricted set of gammadelta T cell receptor
      (TCR) genes. To explore whether this phenomenon of post injury expansion of
      gammadelta T cells occurs in autoimmune-mediated glomerulonephritis, we studied
      gammadelta TCR genes in Heymann nephritis (HN). Gammadelta T cells were increased
      in HN kidneys (p<0.001). These gammadelta T cells predominantly expressed
      Vgamma6/Vdelta1 genes and used canonical matching sequences previously seen in
      the other models of renal injury. Gammadelta T cells from the kidneys expressed
      high levels of TGF-beta, IL-4 and IL-5. The gammadelta T cells from both ADR
      treated and HN kidneys expressed NKG2D, the NK cell-activating receptor. These
      results demonstrate that the majority of gammadelta T cells in the HN kidney use
      a canonical Vgamma6/Vdelta1 TCR--the gammadelta TCR previously described in the
      rat ADR-treated kidney. The restriction in gammadelta TCR seen in two completely
      different models of kidney injury and the expression of an innate activating
      molecule NKG2D suggests that the gammadelta T cells may be responding to tissue
      stress from injury and producing a regulatory response.

PMID- 15259031
TI  - Antigenicity and immunogenicity of peptide analogues of a low affinity peptide of
      the human telomerase reverse transcriptase tumor antigen.
AB  - Human telomerase reverse transcriptase (hTRT) is a potential target for
      therapeutic vaccination against cancer. Therefore, it is critically important to
      identify T cell epitopes useful to induce cytotoxic T cell responses. Here we
      used a positional scanning combinatorial peptide library to identify peptide
      analogues for a previously characterized low affinity hTRT peptide (p572). From
      an initial library containing over 300 billion different peptides and through
      successive rounds of selection, we retained 72 candidate peptide analogues for
      further assessment of antigenicity and in vivo immunogenicity in HLA A2.1
      transgenic mice. While antigenically cross-reactive with p572, only a fraction of
      these peptides was immunogenic in mice. Immunogenicity appeared to correlate with
      the stability of binding to the MHC molecule and the presence of HLA A2.1 anchor
      residues in position 2 and 9. Two peptides differing by five residues from the
      reference p572 (p49 and p50) were more effective than p572 in inducing CTL cross
      reacting with p572 in HLA A2.1-transgenic mice. Both peptides also expanded
      specific CTL in peripheral blood lymphocytes of normal human volunteers ex vivo.
      The present study shows that positional scanning combinatorial peptide libraries
      can be used to identify hTRT peptide analogues for inclusion in a cancer vaccine.

PMID- 15259032
TI  - Rubella virus and birth defects: molecular insights into the viral teratogenesis
      at the cellular level.
AB  - BACKGROUND: In utero rubella virus (RV) infection of a fetus can result in birth
      defects that are often collectively referred to as congenital rubella syndrome
      (CRS). In extreme cases, fetal death can occur. In spite of the availability of a
      safe and effective vaccine against rubella, recent worldwide estimates are that
      more than 100,000 infants are born with CRS annually. RECENT PROGRESS: Recently,
      several significant findings in the field of cell biology, as well as in the RV
      replication and virus-cell interactions, have originated from the authors'
      laboratory, and other researchers have provided insights into RV teratogenesis.
      It has been shown that 1) an RV protein induces cell-cycle arrest by generating a
      subpopulation of tetraploid nuclei (i.e., 4N DNA) cells, perhaps representative
      of the tetraploid state following S phase in the cell cycle, due to its
      interaction with citron-K kinase (CK); 2) RV infection induces apoptosis in cell
      culture, and 3) CK functional perturbations lead to tetraploidy, followed by
      apoptosis, in specific cell types. CONCLUSIONS: Based on several similarities
      between known RV-associated fetal and cellular manifestations and CK deficiency
      associated phenotypes, it is reasonable to postulate that P90-CK interaction in
      RV-infected cells interferes with CK function and induces cell-cycle arrest
      following S phase in a subpopulation, perhaps representative of tetraploid stage,
      which could lead to subsequent apoptosis in RV infection. Taking all these
      observations to the fetal organogenesis level, it is plausible that P90-CK
      interaction could perhaps be one of the initial steps in RV infection-induced
      apoptosis-associated fetal birth defects in utero.

PMID- 15259033
TI  - In vivo hyperglycemia and its effect on Glut-1 expression in the embryonic heart.
AB  - BACKGROUND: Maternal diabetes exposes embryos to periods of hyperglycemia.
      Glucose is important for normal cardiogenesis, and Glut-1 is the predominant
      glucose transporter in the embryo. METHODS: Pregnant mice were exposed to 6 or 12
      hr hyperglycemia during organogenesis using intraperitoneal (IP) injections of D
      glucose on gestational day (GD) 9.5 (plug = GD 0.5). Embryos were examined for
      morphology and total cardiac protein, and embryonic hearts were evaluated for
      Glut-1 protein and mRNA expression immediately after treatment (GD 9.75, GD
      10.0), as well as on GD 10.5 and GD 12.5. RESULTS: IP glucose injections were
      effective in producing sustained maternal hyperglycemia. Maternal hyperglycemia
      for 6 or 12 hr on GD 9.5, followed by normoglycemia, produced a decrease in
      overall size and total cardiac protein in embryos evaluated on GD 10.5 but no
      difference on GD 12.5. Cardiac Glut-1 expression was immediately upregulated in
      embryos exposed to 6 or 12 hr maternal hyperglycemia. On GD 10.5, cardiac Glut-1
      expression was not different in embryos exposed to maternal hyperglycemia for 6
      hr but was downregulated in embryos exposed for 12 hr. On GD 12.5, cardiac Glut-1
      expression in embryos exposed to maternal hyperglycemia on GD 9.5 for 6 or 12 hr,
      followed by normoglycemia, was not different from controls. The temporal pattern
      was the same for Glut-1 protein and mRNA expression. CONCLUSIONS: Hyperglycemia
      induced alterations in Glut-1 expression likely interfere with balance of glucose
      available to the embryonic heart that may affect cardiac morphogenesis.

PMID- 15259035
TI  - Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR)
      polymorphism associated with neural tube defects in southern Brazil.
AB  - BACKGROUND: The importance of metabolic factors in neural tube defects (NTDs) has
      been the focus of many investigations. Several authors have suggested that
      abnormalities in homocysteine metabolism, such as hyperhomocysteinemia, folate
      deficiency, and low vitamin B12, may be responsible for these malformations and
      that both nutritional factors and genetic abnormalities are associated with them.
      METHODS: We conducted a case-control study to investigate the influence of
      biochemical and genetic factors in NTDs in infants in southern Brazil. Levels of
      folate, vitamin B12, total homocysteine (t-Hcy) and the 677C>T and 1298A>C
      polymorphisms of the MTHFR gene were analyzed in 41 NTD child-mother pairs and 44
      normal child-mother control pairs. RESULTS: Subjects in the case group had a
      higher mean blood folate level than those in the control group. The level of
      vitamin B12 was lower in mothers in the NTD group than in control mothers (p =
      0.004). The level of t-Hcy was not different in the two groups, but t-Hcy and
      vitamin B12 were correlated (p = 0.002). There was no difference in the genotype
      distribution for 677C>T and 1298A>C polymorphisms of MTHFR in the case and
      control pairs. The level of t-Hcy was correlated with 677TT. CONCLUSIONS: Despite
      the small sample in this study, we suggest that low vitamin B12 and,
      consequently, hyperhomocysteinemia are important risk factors for NTDs in our
      population.

PMID- 15259034
TI  - Developmental consequences of abnormal folate transport during murine heart
      morphogenesis.
AB  - BACKGROUND: Folic acid is essential for the synthesis of nucleotides and methyl
      transfer reactions. Folic acid-binding protein one (Folbp1) is the primary
      mediator of folic acid transport into murine cells. Folbp1 knockout mouse embryos
      die in utero with multiple malformations, including severe congenital heart
      defects (CHDs). Although maternal folate supplementation is believed to prevent
      human conotruncal heart defects, its precise role during cardiac morphogenesis
      remains unclear. In this study, we examined the role of folic acid on the
      phenotypic expression of heart defects in Folbp1 mice, mindful of the importance
      of neural crest cells to the formation of the conotruncus. METHODS: To determine
      if the Folbp1 gene participates in the commitment and differentiation of the
      cardiomyocytes, relative levels of dead and proliferating precursor cells in the
      heart were examined by flow cytometry, Western blot, and immunohistostaining.
      RESULTS: Our studies revealed that impaired folic acid transport results in
      extensive apoptosis-mediated cell death, which concentrated in the
      interventricular septum and truncus arteriosus, thus being anatomically
      restricted to the two regions of congenital heart defects. Together with a
      reduced proliferative capacity of the cardiomyocytes, the limited size of the
      available precursor cell pool may contribute to the observed cardiac defects.
      Notably, there is a substantial reduction in Pax-3 expression in the region of
      the presumptive migrating cardiac neural crest, suggesting that this cell
      population may be the most severely affected by the massive cell death.
      CONCLUSIONS: Our findings demonstrate for the first time a prominent role of the
      Folbp1 gene in mediating susceptibility to heart defects.

PMID- 15259036
TI  - Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in
      the Philippines.
AB  - BACKGROUND: Vitamin deficiencies induce oral clefts in animal experiments, but
      the role of specific nutrients in human oral clefts is uncertain. METHODS:
      Associations between maternal vitamin B-6 and folate status and risk of
      nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in
      case-control studies at two sites in the Philippines--Negros Occidental and
      Davao. Cases were mothers of affected children and control mothers were those who
      had no children with oral clefts. RESULTS: The risk of having a CL/P-affected
      child increased with increasing tertile of vitamin B-6 deficiency in both Negros
      Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for
      sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI,
      2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers
      with lower versus higher plasma folate levels. Increasing tertiles of plasma
      folate were marginally associated with an increased risk of clefts in both sites
      combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94
      2.70). Increasing tertiles of erythrocyte folate were associated with a decreased
      risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90;
      OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR,
      1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent
      associations between folate status and CL/P risk appeared to be a result of
      statistical interaction between folate, vitamin B-6, and case-control status that
      produced different results in study areas of higher versus lower prevalence of
      vitamin B-6 deficiency. CONCLUSIONS: Poor maternal vitamin B-6 status was
      consistently associated with an increased risk of CL/P at two sites in the
      Philippines. Folate-CL/P associations were inconsistent and may be related to the
      vitamin B-6 status or other characteristics of the populations under study.

PMID- 15259037
TI  - Epidemiologic characteristics of anotia and microtia in California, 1989-1997.
AB  - BACKGROUND: There is a paucity of epidemiologic information about the external
      ear malformations anotia and microtia. METHODS: Using data from a large
      population-based registry, we explored prevalences and maternal/infant
      characteristics associated with anotia and microtia. Data were derived from the
      California Birth Defects Monitoring Program, a population-based active
      surveillance system for collecting information on infants and fetuses with
      congenital malformations using multiple source ascertainment. Approximately 2.5
      million births (live-born and stillborn) occurred during the ascertainment
      period, 1989-1997. Information on maternal and infant/fetal characteristics was
      obtained from California birth certificate and fetal death files. RESULTS: The
      prevalence of anotia/microtia was 2.50 per 10,000 live births and stillbirths.
      Isolated cases, i.e., those live births and stillbirths with no other
      accompanying anomaly diagnoses, revealed a prevalence of 0.63 per 10,000, whereas
      among nonisolated cases, the prevalence was 1.53 per 10,000 live births and
      stillbirths. Prevalences of isolated anotia/microtia were substantially higher
      among U.S.-born Hispanics, foreign-born Hispanics, and Asians compared to non
      Hispanic whites, with relative risks ranging from three- to seven-fold. Similar
      prevalences for maternal race/ethnicity (except for Asians) were observed for
      live births and stillbirths with nonisolated cases of anotia/microtia, but the
      magnitude of risks were lower than those observed for isolated cases. Prevalence
      of nonisolated anotia/microtia was substantially lower among women whose
      education was 12 years or more. CONCLUSIONS: These data reveal descriptive
      epidemiologic features of anotia/microtia most notably substantial risks
      associated with race/ethnic groups and lower maternal education. Additional study
      for factors associated with these characteristics could reveal clues for the
      etiology of these ear anomalies.

PMID- 15259038
TI  - Developmental evaluation of children born to mothers occupationally exposed to
      waste anesthetic gases.
AB  - BACKGROUND: The etiology of developmental delay in children is frequently
      unknown. Increasing evidence supports the possibility that environmental and
      occupational factors might be part of the basis for such delays. This study
      focuses on the development of children born to mothers who were exposed during
      their pregnancy to waste anesthetic gases. METHODS: The study population included
      40 children aged 5-13 years born to female anesthesiologists and nurses working
      in operating rooms (OpRs) exposed to waste anesthetic gases, and 40 unexposed
      children born to female nurses and physicians who worked in hospitals during
      their pregnancy but did not work in OpRs. The unexposed group was matched for
      children's age and gender and maternal occupation (nurses vs. doctors). By means
      of standardized developmental tests, the present study population was evaluated
      for their medical and neurodevelopmental state. Questionnaires were given for the
      detection of attention and activity levels as perceived by the parents.
      Additional questionnaires dealt with information concerning developmental
      milestones, maternal and fetal morbidity, and gynecological history. RESULTS: No
      differences were noted between the groups as newborns or in developmental
      milestones at the age of 5-13 years; however, the mean score of gross motor
      ability was significantly lower in the exposed versus the unexposed group.
      Additionally, the mean score of the DSM-III-R Parent-Teacher Questionnaire (PTQ)
      (i.e., measure of inattention/hyperactivity) was higher in the exposed group. The
      level of exposure, as measured by the number of weekly hours in the OpRs, was
      significantly and negatively correlated with fine motor ability and the score of
      IQ performance. CONCLUSIONS: Our study supports the hypothesis that occupational
      exposure to anesthetic gases might be a risk factor for minor neurological
      deficits of children born to mothers who work in OpRs and therefore indicates the
      need for more studies in this area and perhaps more caution among OpR pregnant
      women and employers.

PMID- 15259039
TI  - Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a
      population from the northern United Kingdom.
AB  - BACKGROUND: A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase
      (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due
      to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white,
      U.S. citizens carrying at least one 2x 28-bp repeat allele have recently been
      shown to be at a four-fold increased risk of spina bifida (SB). We investigated
      the association between this polymorphism and risk of NTD in families affected by
      NTDs and controls from the northern United Kingdom (UK). METHODS: PCR was
      performed on genomic DNA extracted from blood or mouth swabs of family members
      affected by NTDs (mothers, fathers, and cases), and unaffected controls (mothers
      and infants) to determine the number of 28-bp repeat units within the promoter
      region of TYMS. Case-control and TDT analyses of the influence of TYMS genotype
      on risk of NTD, or NTD pregnancy, were conducted. RESULTS: Odds ratio (OR)
      analysis indicated that individuals carrying the 2x 28-bp repeat allele either in
      homozygous or heterozygous form, are not at increased risk of NTDs, or of having
      an NTD affected pregnancy. Control population allele frequencies are seen to be
      markedly different between the U.S. controls and those in this study.
      CONCLUSIONS: TYMS polymorphism appears to be not universally associated with NTD
      risk across Caucasian samples. The elevated risk of spina bifida in U.S. samples
      appears to be driven by an unusually low risk allele (2x 28 bp) frequency in
      control samples. Family based (TDT) testing of U.S. samples is therefore
      advocated.

PMID- 15259041
TI  - Income-related inequality in health and health care in the European Union.

PMID- 15259042
TI  - Explaining the differences in income-related health inequalities across European
      countries.
AB  - This paper provides new evidence on the sources of differences in the degree of
      income-related inequalities in self-assessed health in 13 European Union member
      states. It goes beyond earlier work by measuring health using an interval
      regression approach to compute concentration indices and by decomposing
      inequality into its determining factors. New and more comparable data were used,
      taken from the 1996 wave of the European Community Household Panel. Significant
      inequalities in health (utility) favouring the higher income groups emerge in all
      countries, but are particularly high in Portugal and - to a lesser extent - in
      the UK and in Denmark. By contrast, relatively low health inequality is observed
      in the Netherlands and Germany, and also in Italy, Belgium, Spain Austria and
      Ireland. There is a positive correlation with income inequality per se but the
      relationship is weaker than in previous research. Health inequality is not merely
      a reflection of income inequality. A decomposition analysis shows that the
      (partial) income elasticities of the explanatory variables are generally more
      important than their unequal distribution by income in explaining the cross
      country differences in income-related health inequality. Especially the relative
      health and income position of non-working Europeans like the retired and disabled
      explains a great deal of 'excess inequality'. We also find a substantial
      contribution of regional health disparities to socio-economic inequalities,
      primarily in the Southern European countries.

PMID- 15259043
TI  - Explaining income-related inequalities in doctor utilisation in Europe.
AB  - This paper presents new international comparative evidence on the factors driving
      inequalities in the use of GP and specialist services in 12 EU member states. The
      data are taken from the 1996 wave of the European Community Household Panel
      (ECHP). We examine two types of utilisation (the probability of a visit and the
      conditional number of positive visits) for two types of medical care: general
      practitioner and medical specialist visits using probit, truncated Negbin and
      generalised Negbin models. We find little or no evidence of income-related
      inequity in the probability of a GP visit in these countries. Conditional upon at
      least one visit, there is even evidence of a somewhat pro-poor distribution. By
      contrast, substantial pro-rich inequity emerges in virtually every country with
      respect to the probability of contacting a medical specialist. Despite their
      lower needs for such care, wealthier and higher educated individuals appear to be
      much more likely to see a specialist than the less well-off. This phenomenon is
      universal in Europe, but stronger in countries where either private insurance
      cover or private practice options are offered to purchase quicker and/or
      preferential access. Pro-rich inequity in subsequent visits adds to this access
      inequity but appears more related to regional disparities in utilisation than to
      other factors. Despite decades of universal and fairly comprehensive coverage in
      European countries, utilisation patterns suggest that rich and poor are not
      treated equally.

PMID- 15259044
TI  - On the interpretation of a concentration index of inequality.
AB  - This paper aims to add a more intuitive understanding to the concept of a
      concentration index for measuring relative inequality with an application of
      health-related measures by income. A new redistribution interpretation and an
      existing redistribution interpretation of the Gini are presented and applied to
      the concentration index. Both indicate the share of the total amount of any
      variable that needs redistributing in a particular way from rich to poor (or vice
      versa) to achieve a concentration index equal to zero. The characteristics of
      these redistribution schemes are compared. The paper also draws attention to the
      relationship between a concentration index, a correlation coefficient with
      relative income rank and a coefficient of variation of the variable of interest.
      These relationships are illustrated using data on inequality in dental care
      utilisation in European countries taken from the European Community Household
      Panel survey.

PMID- 15259045
TI  - Determinants of access to physician services in Italy: a latent class seemingly
      unrelated probit approach.
AB  - We examine access to general practitioners and specialists who work in the public
      and private sectors in Italy using a seemingly unrelated system of probits. We
      use a latent class formulation that provides a rich and flexible functional form
      and can accommodate non-normality of response probabilities. The empirical
      analysis shows that patient behavior can be clustered in two latent classes. We
      find that income strongly influences the mix of services. Richer individuals are
      less likely to seek care from GP's and more likely to seek care from specialists,
      and especially private specialists. Health status and societal vulnerability are
      the most important indicators of class membership.

PMID- 15259046
TI  - Access to physician services: does supplemental insurance matter? evidence from
      France.
AB  - In France, public health insurance is universal but incomplete, with private
      payments accounting for roughly 25% of all spending. As a result, most people
      have supplemental private health insurance. We investigate the effects of such
      insurance on the utilization of physician services using data from the 1998
      Enquete sur la sante et la protection sociale, a nationally representative survey
      of the non-institutionalized French population. Our results indicate that
      insurance has a strong and significant effect on the utilization of physician
      services. Individuals with supplemental coverage have substantially more
      physician visits than those without. While French patients have greater freedom
      than patients in other countries to choose to see a specialist rather than a
      general practitioner, we find no evidence that supplemental insurance affects
      this decision.

PMID- 15259047
TI  - The effect of private insurance access on the choice of GP/specialist and
      public/private provider in Spain.
AB  - This paper sheds light into the investigation of differential patterns of
      utilisation of physician services by populations subgroups that is emerging in a
      number of studies. Using Spanish data from the National Health Survey of 1997 we
      try to explain the distinct role of the type of insurance on the choice between
      specialists and GPs and its intertwining with the choice between private and
      public providers. We estimate a two-stages probit to conclude that differences in
      insurance access is the main determinant of both, the choice of sector and the
      kind of physician contacted, giving rise to very different patterns of
      consumption of GP and specialist visits. People with only public insurance go 2.8
      times to the GP per one time that they visit a specialist; individuals with
      duplicate coverage have a ratio of GP/specialist visits equal to 1.4 (the
      combination being public GP and private specialist) and people with only private
      insurance access actually have an 'inverted' pattern of visits: they contact
      specialists more often than GPs. Age, sex and health and public supply
      characteristics also have a distinct and interesting impact on these choices.
      Finally, equity concerns based on the implied assumption that specialists care is
      superior to general practitioner care are discussed.

PMID- 15259048
TI  - Measuring horizontal inequity in Belgian health care using a Gaussian random
      effects two part count data model.
AB  - We estimate the determinants of utilisation of physician and hospital services in
      Belgium using a one- and two-part panel count data model, and a one- and two-part
      pooled count data model. We conclude that the two-part panel count data model is
      most appropriate as it controls for unobserved heterogeneity and allows for a two
      part decision-making process. The estimates of the determinants of utilisation of
      health care are then used to calculate indices of horizontal inequity. We find
      that inequity for general practitioner and hospital services is stable across
      time and in favour of low-income individuals, in the sense that, overall, they
      consume more than one would expect on the basis of their need, albeit the indices
      for hospital care are not significant. Horizontal equity applies to specialist
      care in all years, but from 1999 onwards, some evidence (although not
      statistically significant) of pro-rich inequity is found.

PMID- 15259049
TI  - Measuring inequality in self-reported health-discussion of a recently suggested
      approach using Finnish data.
AB  - Health surveys often include a general question on self-assessed health (SAH),
      usually measured on an ordinal scale with three to five response categories, from
      'very poor' or 'poor' to 'very good' or 'excellent'. This paper assesses the
      scaling of responses on the SAH question. It compares alternative procedures
      designed to impose cardinality on the ordinal responses. These include OLS,
      ordered probit and interval regression approaches. The cardinal measures of
      health are used to compute and decompose concentration indices for income-related
      inequality in health. Results are provided using Finnish data on 15D and the SAH
      questions. Further evidence emerges for the internal validity of a method used in
      a pioneering study by van Doorslaer and Jones which was based on Canadian data on
      the McMaster Health Utility Index Mark III (HUI) and SAH. The study validates the
      conclusions drawn by van Doorslaer and Jones. It confirms that the interval
      regression approach is superior to OLS and ordered probit regression in assessing
      health inequality. However, regarding the choice of scaling instrument, it is
      concluded that the scaling of SAH categories and, consequently, the measured
      degree of inequality, are sensitive to characteristics of the chosen scaling
      instrument.

PMID- 15259050
TI  - To what extent do people prefer health states with higher values? A note on
      evidence from the EQ-5D valuation set.
AB  - The EQ-5D general population valuation set (or 'tariff') is increasingly being
      used in the evaluation of health care interventions and has been recommended by
      the National Institute for Clinical Excellence (NICE) for use in cost-utility
      analyses of health technologies. To be of use to decision-makers, the health gain
      implied by changes in health state values must reflect individual preferences. At
      the simplest level, if State A has a higher mean value than State B, then the
      majority of people should consider a move from B to A to be a good thing. In this
      paper, we examine the extent to which this is true by re-analysing data from the
      general population study used to derive the EQ-5D tariff. We show that, on
      average, the difference in value between two states has to be as large as 0.20
      (on a scale where one represents full and zero represents death) for 70% of
      respondents to agree with the sign of that difference (never mind its size).
      Results such as these have important implications for the use of the EQ-5D tariff
      that has been generated from these data.

PMID- 15259051
TI  - Inhibitors arrest myofibrillogenesis in skeletal muscle cells at early stages of
      assembly.
AB  - A three-step model for myofibrillogenesis has been proposed for the formation of
      myofibrils [Rhee et al., 1994: Cell Motil. Cytoskeleton 28:1-24; Sanger et al.,
      2002: Adv. Exp. Med. 481:89-105]: premyofibril to nascent myofibril to mature
      myofibril. We have found two chemically related inhibitors that will arrest
      development at both the first and second step. Cultured quail embryonic skeletal
      myoblasts were treated with ethyl methane sulfonate (EMS) or 2-aminoethyl
      methanesulfonate (MTSEA+). When the myoblasts fused in the presence of either of
      these compounds, myosheets rather than myotubes formed. Treated cells were fixed
      and immunostained against multiple proteins commonly found in muscle cells.
      Protein expression and localization throughout the myosheet were similar to that
      of developing myotube tips. Cells treated with high concentrations of EMS (10 mM)
      stained for non-muscle myosin II, sarcomeric alpha-actinin, and tropomyosin. No
      zeugmatin (Z-band region of titin) or muscle myosin II antibody staining was
      detected in fibers in this treatment group. These fibers are comparable to
      premyofibrils in control myotubes. At lower concentrations of EMS (7.5 to 5 mM),
      fibers that formed stained for muscle myosin II and titin as well as for non
      muscle myosin IIB, sarcomeric alpha-actinin, and tropomyosin. Muscle myosin II
      was in an unbanded pattern. These fibers are comparable to nascent myofibrils
      observed during normal myofibrillogenesis. Similar effects to those obtained by
      treating cells with EMS were obtained when we treated cultured cells with MTSEA+
      (5 mM) and stained them with sarcomeric alpha-actinin. MTSEA+ is chemically
      related to EMS, and is a well-known inhibitor of ryanodine receptors in skeletal
      muscle cells. Some abnormalities such as nemaline-like rods and other protein
      aggregates also appear within the myosheet during EMS and MTSEA+ treatment.
      Removal of these two inhibitors of myofibrillogenesis allows the premyofibrils
      and nascent myofibrils to form mature myofibrils.

PMID- 15259052
TI  - Keratocyte-like locomotion in amiB-null Dictyostelium cells.
AB  - Starved Dictyostelium amoebae continuously change their shape and they are
      elongated along the front-rear axis during locomotion. In contrast, we found that
      disruption of the amiB gene, which had been identified as a gene required for the
      aggregation process during development, caused these cells to move in a manner
      similar to fish keratocytes. Starved amiB- cells were elongated laterally and had
      one large lamellipodium along the front side arc of the cell. These cells moved
      unidirectionally for long distances maintaining the half-moon shape, and this
      movement followed the predictions of the graded radial extension model, which was
      originally developed to describe the keratocyte movements. Furthermore, the
      distributions of actin, Arp2, and myosin II in amiB- cells were similar to those
      in keratocytes. Therefore, locomotion by keratocytes and amiB- cells appears to
      be driven by similar mechanisms of cytoskeletal regulation. Double knockout cells
      lacking both AmiB and myosin II were still able to move unidirectionally in a
      keratocyte-like manner, although the frequency of those movements was lower.
      Thus, myosin II is dispensable for the unidirectional movement, though it likely
      functions in the maintenance of the characteristic half-moon shape. This mutant
      cell can be a useful tool for further molecular genetic analysis of the mechanism
      of cell locomotion.

PMID- 15259053
TI  - Calmodulin/calmodulin-dependent protein kinase II mediates SAAF-induced motility
      activation of ascidian sperm.
AB  - Ca2+-influx and membrane hyperpolarization by sperm-activating and -attracting
      factor (SAAF) released from the unfertilized egg of the ascidians Ciona cause a
      transient increase in cAMP, which triggers activation of sperm motility. We
      demonstrated here the presence of Ca2+-binding protein, calmodulin (CaM), and CaM
      dependent kinase II (CaMKII) in the sperm. CaM antagonist, W-7, and CaMKII
      inhibitor, KN-93, suppressed SAAF-induced membrane hyperpolarization, increase in
      cAMP, and activation of sperm motility, but inactive analogues of W-7 and KN-93,
      namely W-5 and KN-92, respectively, did not. Subsequent addition of K+ ionophore,
      valinomycin, hyperpolarized the plasma membrane, increased cAMP, and conferred
      motility to the immotile sperm even in the presence of W-7 and KN-93. Addition of
      IBMX activated motility of sperm, which has been immobilized by W-7 and KN-93.
      These suggest that increased [Ca2+]i through influx of Ca2+ by SAAF binds to CaM
      to activate CaMKII. The activated CaMKII may cause membrane hyperpolarization to
      increase cAMP, which triggers the activation of sperm motility in Ciona.

PMID- 15259054
TI  - Auto-reverse nuclear migration in bipolar mammalian cells on micropatterned
      surfaces.
AB  - A novel assay based on micropatterning and time-lapse microscopy has been
      developed for the study of nuclear migration dynamics in cultured mammalian
      cells. When cultured on 10-20-microm wide adhesive stripes, the motility of C6
      glioma and primary mouse fibroblast cells is diminished. Nevertheless, nuclei
      perform an unexpected auto-reverse motion: when a migrating nucleus approaches
      the leading edge, it decelerates, changes the direction of motion, and
      accelerates to move toward the other end of the elongated cell. During this
      process, cells show signs of polarization closely following the direction of
      nuclear movement. The observed nuclear movement requires a functioning
      microtubular system, as revealed by experiments disrupting the main cytoskeletal
      components with specific drugs. On the basis of our results, we argue that auto
      reverse nuclear migration is due to forces determined by the interplay of
      microtubule dynamics and the changing position of the microtubule organizing
      center as the nucleus reaches the leading edge. Our assay recapitulates specific
      features of nuclear migration (cell polarization, oscillatory nuclear movement),
      while it allows the systematic study of a large number of individual cells. In
      particular, our experiments yielded the first direct evidence of reversive
      nuclear motion in mammalian cells, induced by attachment constraints.

PMID- 15259055
TI  - Dynamics of cell adhesion and motility in living cells is altered by a single
      amino acid change in E-cadherin fused to enhanced green fluorescent protein.
AB  - E-Cadherin regulates epithelial cell adhesion and is critical for the maintenance
      of tissue integrity. In sporadic diffuse-type gastric carcinoma, mutations of the
      E-cadherin gene are frequently observed that predominantly affect putative
      calcium binding motifs located in the linker region between the second and third
      extracellular domains. A single amino acid change (D370A) as found in a gastric
      carcinoma patient reduces cell adhesion and up-regulates cell motility. To study
      the effect of this mutation on the dynamics of cell adhesion and motility in
      living cells, enhanced green fluorescent protein (EGFP) was C-terminally fused to
      E-cadherin. The resulting mutant E-cadherin-EGFP fusion protein with a point
      mutation in exon 8 (p8-EcadEGFP) and a wild-type E-cadherin-EGFP fusion construct
      (wt-EcadEGFP) were expressed in human MDA-MB-435S cells. Fluorescent images were
      acquired by time-lapse laser scanning microscopy and E-cadherin was visualized
      during contact formation and in moving cells. Spatial and temporal localization
      of p8- and wt-EcadEGFP differed significantly. While wt-EcadEGFP was mainly
      localized at lateral membranes of contacting cells and formed E-cadherin puncta
      and plaques, p8-EcadEGFP-expressing cells frequently formed transient cell-cell
      contacts. During random cell migration, p8-EcadEGFP was found in lamellipodia. In
      contrast, wt-EcadEGFP localized at lateral cell-cell contact sites in low or non
      motile cells. Inhibition of the epidermal growth factor (EGF) receptor, which
      plays a major role in lamellipodia formation and cell migration, reduced the
      motility of p8-EcadEGFP-expressing cells and caused lateral membrane staining of
      p8-EcadEGFP. Conversely, EGF induced cell motility and caused formation of
      lamellipodia that were E-cadherin positive. In conclusion, our data show that
      mutant E-cadherin significantly alters the dynamics of cell adhesion and motility
      in living cells and interferes with the formation of stable cell-cell contacts.

PMID- 15259056
TI  - NDP kinase moves into developing primary cilia.
AB  - Inmunofluorescence staining of murine NIH3T3 fibroblasts grown at high density
      shows that conventional nucleoside diphosphate (NDP) kinases A and B localize to
      a sensory organelle, the primary cilium. Similar results are obtained with
      Xenopus A6 kidney epithelial cells, suggesting that NDP kinases are a universal
      component of the primary cilium. The translocation of NDP kinase into primary
      cilia depends on size, taking place only when cilia reach a critical length of 5
      6 microm. In mature cilia, NDP kinases are distributed along the ciliary shaft in
      a punctate pattern that is distinct from the continuous staining observed with
      acetylated alpha-tubulin, a ciliary marker and axonemal component. Isolation of a
      fraction enriched in primary cilia from A6 cells led to the finding that ciliary
      NDP kinase is enzymatically active, and is associated with the membrane and the
      matrix, but not the axoneme. In contrast, acetylated alpha-tubulin is found in
      the axoneme and, to a lesser extent, in the membrane. Based on the tightly
      regulated translocation process and the subciliary distribution pattern of NDP
      kinase, we propose that it plays a role in the elongation and maintenance of
      primary cilia by its ability to regenerate the GTP utilized by ciliary
      microtubule turnover and transmembrane signaling.

PMID- 15259058
TI  - Clinicopathologic analysis of esophageal and cardiac cancers and survey of
      molecular expression on tissue arrays in Chaoshan littoral of China.
AB  - AIM: To investigate clinical and pathologic data of esophageal carcinoma (EC) and
      cardiac carcinoma (CC) among residents in Chaoshan region of China. METHODS:
      Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC
      in the Chaoshan population were collected and analyzed. Moreover, Chaoshan
      esophageal carcinoma tissue arrays were made for high-throughput study. RESULTS:
      Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average
      age of the occurrence of EC was 54.6 years, and of CC was 58.1 years. For both EC
      and CC, age at diagnosis was a little younger in Chaoshan region than in most
      other areas. The most commonly affected site of esophageal carcinoma was the
      middle third of esophagus (72.0%); the second was the lower third (15.3%). The
      main gross type of esophageal carcinoma was ulcerative type (41.50%); the
      medullary type was the second (39.6%). Squamous cell carcinoma accounted for the
      overwhelming majority of esophageal cancer (96.4%); adenocarcinoma accounted for
      the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal
      carcinoma tissue arrays were easily for high-throughput study, and tissue cores
      with a diameter of 1.5 mm could better keep more structure for molecular
      expression study. CONCLUSION: Both EC and CC are common in males. The average
      occurrence age of EC and CC is younger in Chaoshan than in most other regions of
      China. The most commonly affected site of esophageal carcinoma was the middle
      third of esophagus (72.0%). Squamous cell carcinoma accounted for the
      overwhelming majority of esophageal cancer; adenocarcinoma accounted for the
      overwhelming majority of cardiac carcinoma. Tissue arrays technology is
      applicable for rapid molecular profiling of large numbers of cancers in a single
      experiment.

PMID- 15259057
TI  - Hepatitis E: an overview and recent advances in vaccine research.
AB  - Hepatitis E virus (HEV) is an unclassified, small, non-enveloped RNA virus, as a
      causative agent of acute hepatitis E that is transmitted principally via the
      fecal-oral route. The virus can cause large water-born epidemics of the disease
      and sporadic cases as well. Hepatitis E occurs predominantly in developing
      countries, usually affecting young adults, with a high fatality rate up to 15-20%
      in pregnant women. However, no effective treatment currently exists for hepatitis
      E, and the only cure is prevention. But so far there are no commercial vaccines
      for hepatitis E available in the world. Although at least four major genotypes of
      HEV have been identified to date, only one serotype of HEV is recognized. So
      there is a possibility to produce a broadly protective vaccine. Several studies
      for the development of an effective vaccine against hepatitis E are in progress
      and the best candidate at present for a hepatitis E vaccine is a recombinant HEV
      capsid antigen expressed in insect cells from a baculovirus vector. In this
      article, the recent advances of hepatitis E and the development of vaccine
      research for HEV including recombinant protein vaccine, DNA vaccine and the
      recombinant hepatitis E virus like particles (rHEV VLPs) are briefly reviewed.

PMID- 15259059
TI  - Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas.
AB  - AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human
      esophageal squamous cell carcinoma. METHODS: Quantitative reverse transcription
      polymerase chain reaction (RT-PCR), western blotting, immunohistoc-hemistry and
      immunofluorescence were used to assess the expression level of COX-2 in
      esophageal tissue. RESULTS: COX-2 mRNA levels were increased by >80-fold in
      esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue.
      COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma
      tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was
      performed to directly show expression of COX-2 in tumor tissue. CONCLUSION: These
      results suggest that COX-2 may be an important factor for esophageal cancer and
      inhibition of COX-2 may be helpful for prevention and possibly treatment of this
      cancer.

PMID- 15259060
TI  - Gastric malignancies in Northern Jordan with special emphasis on descriptive
      epidemiology.
AB  - AIM: To study the epidemiology of gastric malignancies in Jordan as a model for
      Middle East countries where such data is scarce. METHODS: Pertinent
      epidemiological and clinicopathological data for 201 patients with gastric
      malignancy in north of Jordan between 1991 and 2001 were analyzed. RESULTS: Male:
      female ratio was 1.8:1. The mean age was 61.2 years, and 8.5% of the patients
      were younger than 40 years of age. The overall age-adjusted incidence was
      5.82/100 000 population/year. The age specific incidence for males raised from
      1.48 in those aged 30-39 years to 72.4 in those aged 70-79 years.
      Adenocarcinomas, gastric lymphomas, malignant stromal tumors, and carcinoids were
      found in 87.5%, 8%, 2.5%, and 2% respectively. There was an average of 10.1-month
      delay between the initial symptoms and the diagnosis. Only 82 patients underwent 
      curative   gastrectomy. Among adenocarcinoma groups, Lauren intestinal type was
      the commonest (72.2%) and the distal third was the most common localization
      (48.9%). The mean follow up for patients with gastric adenocarcinoma was 25.1 mo
      (range 1-132 mo). The 5-year survival rates for stages I (n=15), II (n=41), III
      (n=59), and IV (n=53) were 67.3%, 41.3%, 5.7%, and 0% respectively (P=0.0001).
      The overall 5 year survival was 21.1%. CONCLUSION: Despite low incidence, some
      epidemiological features of gastric cancer in Jordan mimic those of high-risk
      areas. Patients are detected and treated after a relatively long delay. No
      justification in favor of a possible gastric cancer screening effort in Jordan is
      supported by our study; rather, the need of an earlier diagnosis and subsequent
      better care.

PMID- 15259061
TI  - Identification of tumor markers using two-dimensional electrophoresis in gastric
      carcinoma.
AB  - AIM: To study the differential expression of proteins in normal and cancerous
      gastric tissues, and further identify new molecular markers for diagnosis and
      prognosis of gastric carcinoma, as well as develop new therapeutic targets of the
      disease. METHODS: Matched pairs of tissues from 6 gastric cancer patients were
      analyzed for their two-dimensional electrophoresis (2DE) profiles. Soluble
      fraction proteins from human normal and cancerous gastric tissue were separated
      in the first dimension by isoelectric focusing on immobilized pH gradient (IPG,
      pH3-10) strips, and by 125 g/L sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) in the second dimension with silver nitrate staining.
      Protein differential expression was analyzed by use of image analysis software to
      find out candidates for gastric cancer-associated proteins. RESULTS: Nine protein
      spots overexpressed in tumor tissues as compared with noncancerous regions. In
      the next step, 9 tumor-specific spots were cut off from Coomassie Brilliant Blue
      staining gels, digested in gel with L-1-tosylamide-2-phenylethyl chloromethyl
      ketone (TPCK)-trypsin. Protein identification was done by peptide mass
      fingerprinting with matrix assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF-MS). In total, 5 tumor-specific protein spots
      corresponding to 5 different polypeptide chains were identified, including
      annexin V, carbonic anhydrase, prohibitin, fibrin beta and fibrinogen fragment D.
      Among these 5 spots, the potential significance of the differential expressions
      is discussed. CONCLUSION Differential expression analysis of proteomes may be
      useful for the development of new molecular markers for diagnosis and prognosis
      of gastric carcinoma.

PMID- 15259062
TI  - Therapeutic effects and prognostic factors in three-dimensional conformal
      radiotherapy combined with transcatheter arterial chemoembolization for
      hepatocellular carcinoma.
AB  - AIM: To evaluate the therapeutic efficacy of three-dimensional conformal
      radiotherapy (3D-CRT) combined with transcatheter arterial chemoembolization
      (TACE) on the patients with hepatocellular carcinoma (HCC). METHODS: Between 1998
      and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63
      patients had a Okuda stage I lesion and 31 patients had stage II. The median
      tumor size was 10.7 cm (range 3.0-18 cm), and liver cirrhosis was present in all
      the patients. There were 43 cases of class A and 51 class B. TACE was performed
      using lipiodol, 5-fluorouracil, cisplatin, doxorubicin hydrochloride and
      mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE
      only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after
      TACE. All patients were irradiated with a stereotactic body frame and received 4
      8 Gy single high-dose radiation for 8-12 times at the isocenter during a period
      of 17-26 d (median 22 d). RESULTS: The median follow-up was 37 mo (range 10-48
      mo) after diagnosis. The response rate was 90.5%. The overall survival rate at 1
      , 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median
      survival of 25 mo. On univariate analysis, age (P=0.026), Child-Pugh
      classification for cirrhosis of liver (P=0.010), Okuda stage (P=0.026), tumor
      size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose
      (P=0.000) proved to be significant factors for survival. On multivariate
      analysis, age (P=0.024), radiation dose (P=0.001), and tumor size (P=0.000) were
      the significant factors. CONCLUSION: 3D-CRT combined with TACE is an effective
      and feasible approach for HCC. Age, radiation dose and tumor size were found to
      be significant prognostic factors for survival of patients with HCC treated by 3D
      CRT combined with TACE. Further study for HCC is needed to improve the treatment
      efficacy.

PMID- 15259063
TI  - Transfection of IL-2 and/or IL-12 genes into spleen in treatment of rat liver
      cancer.
AB  - AIM: To test the efficacy of gene therapy in rat liver tumor. METHODS: A
      retroviral vector GCIL12EIL2PN encoding human IL-2 (hIL-2) and mouse IL-12 (mIL
      12) fused gene and its packaging cell were constructed. The packaging cell lines
      contained of IL-2 and/or IL-12 genes were injected intrasplenically to transfect
      splenocyte at different time. The therapeutic effect, immune function and toxic
      effect were evaluated. RESULTS: The average survival times of the 4 groups using
      IL genes at days 1, 3, 5 and 7 after tumor implantation were 53.3+/-3.7, 49.3+/
      4.2, 31.0+/-2.1 and 24.3+/-1.4 d respectively in IL-2/IL-12 fused gene group,
      25.0+/-2.5, 23.5+/-2.0, 18.3+/-2.4 and 12.0+/-1.8 d respectively in IL-2 gene
      treatment group, and 39.0+/-4.8, 32.0+/-3.9, 23.0+/-2.5 and 19.4+/-2.1 d
      respectively in IL-12 gene treatment group (P<0.01, n=10). In the IL-12/IL-2
      fused gene treatment group, 30% of rats treated at days 1 and 3 survived more
      than 60 d and serum mIL-12 and hIL-2 levels were still high at day 3 after
      treatment. Compared with IL alone, NK cell activity was strongly stimulated by IL
      2/IL-12 gene. Microscopy showed that livers were infiltrated by a number of
      lymphocytes. CONCLUSION: IL-2 and/or IL-12 genes injected directly into spleen
      increase serum IL-2 and IL-12 levels and enhance the NK cell activity, which may
      inhibit the liver tumor growth. The therapy of fused gene IL-2/IL-12 is of low
      toxicity and relatively high NK cell activity. Our data suggest that IL-2/IL-12
      fused gene may be a safe and efficient gene therapy for liver tumor. The gene
      therapy should be administrated as early as possible.

PMID- 15259064
TI  - Combined gene therapy of endostatin and interleukin 12 with polyvinylpyrrolidone
      induces a potent antitumor effect on hepatoma.
AB  - AIM: To study the antitumor effect of combined gene therapy of endostatin and
      interleukin 12 (IL-12) with polyvinylpyrrolidone (PVP) on mouse transplanted
      hepatoma. METHODS: Mouse endostatin eukaryotic plasmid (pSecES) with a mouse
      Igkappa signal sequence inside and mouse IL-12 eukaryotic plasmid (pmIL-12) were
      transfected into BHK-21 cells respectively. Endostatin and IL-12 were assayed by
      ELISA from the supernant and used to culture endothelial cells and spleen
      lymphocytes individually. Proliferation of the latter was evaluated by MTT. H22
      cells were inoculated into the leg muscle of mouse, which was injected
      intratumorally with pSecES/PVP, pmIL-12/PVP or pSecES+pmIL-12/PVP repeatedly.
      Tumor weight, serum endostatin and serum IL-12 were assayed. Tumor infiltrating
      lymphocytes, tumor microvessel density and apoptosis of tumor cells were also
      displayed by HE staining, CD31 staining and TUNEL. RESULTS: Endostatin and IL-12
      were secreted after transfection, which could inhibit the proliferation of
      endothelial cells or promote the proliferation of spleen lymphocytes. Tumor
      growth was highly inhibited by 91.8% after injection of pSecES+pmIL-12/PVP
      accompanied by higher serum endostatin and IL-12, more infiltrating lymphocytes,
      fewer tumor vessels and more apoptosis cells compared with injection of
      pSecES/PVP, pmIL-12/PVP or vector/PVP. CONCLUSION: Mouse endostatin gene and IL
      12 gene can be expressed after intratumoral injection with PVP. Angiogenesis of
      hepatoma can be inhibited synergisticly, lymphocytes can be activated to
      infiltrate, and tumor cells are induced to apoptosis. Hepatoma can be highly
      inhibited or eradiated.

PMID- 15259065
TI  - Analysis of clinical effect of high-intensity focused ultrasound on liver cancer.
AB  - AIM: To evaluate the clinical effect of high-intensity focused ultrasound (HIFU)
      in the treatment of patients with liver cancer. METHODS: HIFU treatment was
      performed in 100 patients with liver cancer under general anesthesia and by a
      targeted ultrasound. Evaluation of efficacy was made on the basis of clinical
      symptoms, liver function tests, AFP, MRI or CT before and after the treatment.
      RESULTS: After HIFU treatment, clinical symptoms were relieved in 86.6%(71/82) of
      patients. The ascites disappeared in 6 patients. ALT (95+/-44) U/L and AST (114+/
      58) U/L before HIFU treatment were reduced to normal in 83.3%(30/36) and
      72.9%(35/48) patients, respectively, after the treatment. AFP was lowered by more
      than 50% in 65.3%(32/49) patients. After HIFU treatment, MRI or CT findings
      indicated coagulation necrosis and blood supply reduction or disappearance of
      tumor in the target region. CONCLUSION: HIFU can efficiently treat the patients
      with liver cancer. It will offer a significant noninvasive therapy for local
      treatment of liver tumor.

PMID- 15259066
TI  - Honokiol induces apoptosis through p53-independent pathway in human colorectal
      cell line RKO.
AB  - AIM: To investigate the signal pathway of honokiol-induced apoptosis on human
      colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes
      were involved in honokiol-treated RKO cells. METHODS: Cell cycle distribution and
      subdiploid peak were analyzed with a flow cytometer and DNA fragment with
      electrophoresis on agarose gels. Transcriptional level of Bax, Bcl-2, Bid and Bcl
      xl was accessed by RT-PCR. Western blotting was used to measure p53 protein
      expression and other factors related to apoptosis. Proliferation inhibition of
      two cell lines (RKO, SW480) with high expression of p53 and one cell line with
      p53 negative expression (LS180) was monitored by MTT assay. RESULTS: Honokiol
      induced RKO cell apoptosis in a dose-dependent manner. The mRNA expression level
      and protein level of Bid were up-regulated while that of Bcl-xl was down
      regulated, but no changes in Bax and Bcl-2 were observed. Western blotting showed
      p53 expression had no remarkable changes in honokiol-induced RKO cell apoptosis.
      LS180 cells treated with honokiol exhibited apparent growth inhibition like RKO
      cells and Sw480 cells. CONCLUSION: Honokiol can induce RKO cells apoptosis
      through activating caspase cascade by p53-indepenent pathway.

PMID- 15259067
TI  - Natural history of chronic hepatitis C in patients on hemodialysis: case control
      study with 4-23 years of follow-up.
AB  - AIM: Hepatitis C virus (HCV) infection is very common among end-stage kidney
      disease patients on hemodialysis, but its natural history is not known. METHODS:
      In this study, 189 dialysis patients (case) positive for HCV antibodies who were
      followed up for more than 4 years were compared with twice as many sex/age
      matched controls with chronic hepatitis C who were diagnosed in the same month as
      the case and followed up for comparable periods. The longest follow-up was 23
      years in dialysis cases. The disease activities were graded into "asymptomatic"
      if ALT was less than 40 (35 in cases) IU/L, "low activities" if ALT was 40 (35)
      79 IU/L, and "high activities" if ALT was above 80 IU/L during the last or latest
      4 year period. RESULTS: All 25 dialysis cases who were followed up for more than
      15 years were asymptomatic and 15 of them were negative for HCV RNA. Of the 50
      controls followed up for more than 15 years, 34 had high activities, and none
      cleared HCV RNA. There were 60 controls who were asymptomatic, but they were all
      positive for HCV RNA, while 22.3% of asymptomatic dialysis cases were RNA
      negative. No dialysis patients with chronic hepatitis C progressed to cirrhosis,
      whereas the disease progressed to cirrhosis in more than one quarter of the
      controls. These differences were highly significant (P<0.0001). CONCLUSION:
      Chronic hepatitic C among hemodialysis patients is mild in disease activity, and
      is not progressive, perhaps due to immunological abnormalities in these patients.
      Hepatic C virus is frequently cleared in asymptomatic dialysis patients during a
      long course. A possible mechanism for viral clearance is viral particle
      destruction on the surface of the dialyzer membrane.

PMID- 15259068
TI  - Initial steroid-free immunosuppression after liver transplantation in recipients
      with hepatitis C virus related cirrhosis.
AB  - AIM: Steroids can increase hepatitis C virus (HCV) replication. After liver
      transplantation (LTx), steroids are commonly used for immunosuppression and acute
      rejection is usually treated by high steroid dosages. Steroids can worsen the
      outcome of recurrent HCV infection. Therefore, we evaluated the outcome of HCV
      infected liver recipients receiving initial steroid-free immunosuppression.
      METHODS: Thirty patients undergoing LTx received initial steroid-free
      immunosuppression. Indication for LTx included 7 patients with HCV related
      cirrhosis. Initial immunosuppression consisted of tacrolimus 2X0.05 mg/kg.d po
      and mycophenolate mofetil (MMF) 2X15 mg/kg.d po. The tacrolimus dosage was
      adjusted to trough levels in the target range of 10-15 microg/L during the first
      3 mo and 5-10 microg/L thereafter. Manifestations of acute rejection were
      verified histologically. RESULTS: Patient and graft survival of 30 patients
      receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2
      years. Acute rejection occurred in 8/30 patients, including 1 HCV infected
      recipient. All HCV-infected patients had HCV genotype II (1b). HCV seropositivity
      occurred within the first 4 mo after LTx. The virus load was not remarkably
      increased during the first year after LTx. Histologically, grafts had no severe
      recurrent hepatitis. CONCLUSION: From our experience, initial steroid-free
      immunosuppression does not increase the risk of acute rejection in HCV infected
      liver recipients. Furthermore, none of the HCV infected patients developed
      serious chronic liver diseases. It suggests that it may be beneficial to avoid
      steroids in this particular group of patients after LTx.

PMID- 15259069
TI  - Genotype and phylogenetic characterization of hepatitis B virus among multi
      ethnic cohort in Hawaii.
AB  - AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been
      evaluated previously. The aim of the present study was to evaluate the
      distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS:
      Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by
      genetic methods. Three complete genomes and 61 core promoter/precore regions of
      HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61
      carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C.
      Genotypes A, B and C were obtained from the carriers whose ethnicities were
      Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian,
      respectively. All cases of genotype B were composed of recombinant strains with
      genotype C in the precore plus core region named genotype Ba. HBeAg was detected
      more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and
      basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in
      genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at
      nucleotide (nt) position 1858 (C-1858). However there was no significant
      difference in clinical characteristics between C-1858 and T-1858 variants. Based
      on complete genome sequences, phylogenetic analysis revealed one patient of
      Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia
      with T-1858. In addition, two strains from Asian ethnicities were clustered with
      known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C
      are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution
      of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

PMID- 15259070
TI  - HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding.
AB  - AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21
      promoter and explore its possible mechanism for influencing p53 function.
      METHODS: p53 function of transactivation on p21 promoter was studied with a
      luciferase reporter system in which the luciferase gene is driven by p21
      promoter, and the p53-DNA binding ability was observed with the use of
      electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A
      expression vectors were used to transfect hepatoma cell lines to observe whether
      HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence
      and p53 transactivation on p21 promoter. Western blot experiment was used for
      detection of HCV NS5A and p53 proteins expression. RESULTS: Relative luciferase
      activity driven by p21 promoter increased significantly in the presence of
      endogenous p53 protein. Compared to the control group, exogenous p53 protein also
      stimulated p21 promoter driven luciferase gene expression in a dose-dependent
      way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53
      transactivation on p21 promoter with increase of the dose of HCV NS5A expression
      plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA
      sequence and, when co-transfected with increased dose of HCV NS5A expression
      vector, the p53 binding affinity to its DNA gradually decreased and finally
      disappeared. Between the Huh 7 cells transfected with p53 expression vector alone
      or co-transfected with HCV NS5A expression vector, there was no difference in the
      p53 protein expression. CONCLUSION: HCV NS5A inhibits p53 transactivation on p21
      promoter through abrogating p53 binding affinity to its specific DNA sequence. It
      does not affect p53 protein expression.

PMID- 15259071
TI  - Early diagnosis of bacterial and fungal infection in chronic cholestatic
      hepatitis B.
AB  - AIM: To investigate the early diagnostic methods of bacterial and fungal
      infection in patients with chronic cholestatic hepatitis B. METHODS: One hundred
      and one adult in-patients with chronic hepatitis B were studied and divided into
      3 groups: direct bilirubin (DBil)/total bilirubin (TBil) > or = 0.5, without
      bacterial and fungal infection (group A, n=38); DBil/TBil <0.5, without bacterial
      and fungal infection (group B, n=23); DBil/TBil> or = 0.5, with bacterial or
      fungal infection (group C, n=40). The serum biochemical index and pulse rate were
      analyzed. RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP) and DBil/ALP
      in group A increased compared with that in group B. The level of ALP in group C
      decreased compared with that in group A, whereas the level of TBil, DBil and
      DBil/ALP increased (ALP: 156+/-43, 199+/-68, respectively, P<0.05; TBil: 370+/
      227, 220+/-206, respectively, P<0.01; DBil: 214+/-143, 146+/-136, respectively,
      P<0.01; DBil/ALP: 1.65+/-1.05, 0.78+/-0.70, respectively, P<0.001). The level of
      DBil and infection affected DBil/ALP. Independent of the effect of DBil,
      infection caused DBil/ALP to rise (P<0.05). The pulse rate in group A decreased
      compared with that in group B (63.7+/-6.4, 77.7+/-11.4, respectively, P<0.001),
      and the pulse rate in group C increased compared with that in group A (81.2+/
      12.2, 63.7+/-6.4, respectively, P<0.001). The equation (infection=0.218 pusle
      rate +1.064 DBil/ALP -16.361), with total accuracy of 85.5%, was obtained from
      stepwise logistic regression. Pulse rate (> or =80/min) and DBil/ALP (> or =1.0)
      were used to screen infection. The sensitivity was 62.5% and 64.7% respectively,
      and the specificity was 100% and 82.8% respectively. CONCLUSION: Bacterial and
      fungal infection deteriorate jaundice and increase pulse rate, decrease serum ALP
      and increase DBil/ALP. Pulse rate, DBil/ALP and the equation (infection=0.218
      pusle rate+1.064 DBil/ALP-16.361) are helpful to early diagnosis of bacterial and
      fungal infection in patients with chronic cholestatic hepatitis B.

PMID- 15259072
TI  - Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor
      kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter
      pylori-infected non-cardiac gastric adenocarcinoma.
AB  - AIM: Several epidemiological studies have demonstrated a close association
      between Helicobacter pylori (H pylori) infection and non-cardiac carcinoma of the
      stomach. H pylori infection induces active inflammation with neutrophilic
      infiltrations as well as production of oxygen free radicals that can cause DNA
      damage. The DNA damage induced by oxygen free radicals could have very harmful
      consequences, leading to gene modifications that are potentially mutagenic and/or
      carcinogenic. The aims of the present study were to assess the effect of H pylori
      infection on the expression of inducible nitric oxidative synthase (iNOS) and the
      production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative
      DNA injury in human gastric mucosa with and without tumor lesions, and to assess
      the possible factors affecting cell death signaling due to oxidative DNA damage.
      METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens
      were obtained from surgical resection. We determined the level of 8-OHdG
      formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death
      signaling (including nuclear factor-kappaB(NFkappaB), MEKK-1, Caspase 3, B Cell
      lymphomal leukemia-2 (Bcl-2), inhibitor of apoptosis protein (IAP) and myeloid
      cell leukemia-1 (Mcl-1)) by Western-blot assay. RESULTS: The concentrations of 8
      OHdG, iNOS, NFkappaB, Mcl-1 and IAP were significantly higher in cancer tissues
      than in adjacent non-cancer tissues. In addition, significantly higher
      concentrations of 8-OHdG, iNOS, NFkappaB, Mcl-1 and IAP were detected in patients
      infected with H pylori compared with patients who were not infected with H
      pylori. Furthermore, 8-OHdG, iNOS, NFkappaB, Mcl-1 and IAP concentrations were
      significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients.
      CONCLUSION: Chronic H pylori infection induces iNOS expression and subsequent DNA
      damage as well as enhances anti-apoptosis signal transduction. This sequence of
      events supports the hypothesis that oxygen-free radical-mediated damage due to H
      pylori plays a pivotal role in the development of gastric carcinoma in patients
      with chronic gastritis.

PMID- 15259073
TI  - Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion
      induced liver injury in rats via nitric oxide.
AB  - AIM: To determine whether Saiko-keishi-to (TJ-10), a Japanese herbal medicine,
      could protect liver injury induced by gut ischemia/reperfusion (I/R), and to
      investigate the role of NO. METHODS: Male Wistar rats were exposed to 30-min gut
      ischemia followed by 60 min of reperfusion. Intravital microscopy was used to
      monitor leukocyte recruitment. Plasma tumor necrosis factor (TNF) levels and
      alanine aminotransferase (ALT) activities were measured. TJ-10 1 g/(kg.d) was
      intragastrically administered to rats for 7 d. A NO synthase inhibitor was
      administered. RESULTS: In control rats, gut I/R elicited increases in the number
      of stationary leukocytes, and plasma TNF levels and ALT activities were mitigated
      by pretreatment with TJ-10. Pretreatment with the NO synthase inhibitor
      diminished the protective effects of TJ-10 on leukostasis in the liver, and the
      increase of plasma TNF levels and ALT activities. Pretreatment with TJ-10
      increased plasma nitrite/nitrate levels. CONCLUSION: TJ-10 attenuates the gut I/R
      induced hepatic microvascular dysfunction and sequential hepatocellular injury
      via enhancement of NO production.

PMID- 15259074
TI  - KAI1 gene expression in colonic carcinoma and its clinical significances.
AB  - AIM: To investigate KAI1 gene expression in the progression of human colonic
      carcinoma and its clinical significances. METHODS: KAI1 expression was detected
      by in situ hybridization and immunohistochemistry in the 4 established cell lines
      of colorectal carcinoma with different metastatic potentials, and in 80 specimens
      of colonic carcinoma, 21 colonic carcinoma specimens with lymphatic metastasis
      and 20 controls of normal colonic mucosa. RESULTS: The expressions of KAI1 in
      HT29 and SW480 cell lines were higher than those in LoVo and SW620. The
      expression of KAI1 gene was significantly higher in colorectal carcinoma compared
      with normal colonic mucosa and lymphatic metastasis (chi(2)=46.838, P<0.01). The
      expression of KAI1 gene had no relationship with histological grade. The KAI1
      expressions in Dukes A and B carcinoma were higher at both mRNA and protein
      levels compared to Dukes C carcinoma (chi(2)=16.061, P<0.05). The expression of
      KAI1 in colonic carcinoma specimens with lymphatic metastasis was almost lost.
      The results of in situ hybridization were in concordance with
      immunohistochemistry. CONCLUSION: KAI1 is highly related to the metastasis of
      colonic carcinoma and may be a useful indicator of metastasis in colonic
      carcinoma.

PMID- 15259075
TI  - Influence of serum from liver-damaged rats on differentiation tendency of bone
      marrow-derived stem cells.
AB  - AIM: Recent studies in both rodents and humans indicated that bone marrow (BM)
      derived stem cells were able to home to the liver after they were damaged and
      demonstrated plasticity in becoming hepatocytes. However, the question remains as
      to how these stem cells are activated and led to the liver and where the signals
      initiating the mechanisms of activation and differentiation of stem cells
      originate. The aim of this study was to investigate the influence of serum from
      liver-damaged rats on differentiation tendency of bone marrow-derived stem cells.
      METHODS: Serum samples were collected from rats treated with a 2
      acetylaminofluorene (2-AAF) /carbon tetrachloride (CCl(4)) program for varying
      time points and then used as stimulators of cultured BM stem cells. Expression of
      M(2)- and L-type isozymes of rat pyruvate kinase, albumin as well as integrin
      beta1 were then examined by reverse transcription polymerase chain reaction (RT
      PCR) to estimate the differentiation state of BM stem cells. RESULTS: Expression
      of M(2)-type isozyme of pyruvate kinase (M(2)-PK), a marker of immature
      hepatocytes, was detected in each group stimulated with experimental serum, but
      not in controls including mature hepatocytes, BM stem cells without serum
      stimulation, and BM stem cells stimulated with normal control serum. As a marker
      expressed in the development of liver, the expression signal of integrin-beta1
      was also detectable in each group stimulated with experimental serum. However,
      expression of L-type isozyme of pyruvate kinase (L-PK) and albumin, marker
      molecules of mature hepatocytes, was not detected in groups stimulated with
      experimental serum. CONCLUSION: Under the influence of serum from rats with liver
      failure, BM stem cells begin to differentiate along a direction to hepatocyte
      lineage and to possess some features of immature hepatocytes.

PMID- 15259076
TI  - Pathophysiological significance of a reaction in mouse gastrointestinal tract
      associated with delayed-type hypersensitivity.
AB  - AIM: To explore the pathophysiological significance of delayed type
      hypersensitivity (DTH) reaction in mouse gastrointestinal tract induced by an
      allergen 2,4-dinitrochlorobenzene (DNCB). METHODS: BALB/c mice were randomly
      divided into control and DTH(1-6) groups. After sensitized by DNCB smeared on the
      abdominal skin, the mice were challenged with DNCB by gavage or enema. The
      weight, stool viscosity and hematochezia were observed and accumulated as disease
      active index (DAI) score; the gastrointestinal motility was represented by active
      charcoal propulsion rate; the colon pathological score was achieved by
      macropathology and HE staining of section prepared for microscopy; and the
      leukocyte migration inhibitory factor (LMIF) activity was determined by indirect
      capillary assay of the absorbance (A) of migrated leukocytes. RESULTS: Active
      charcoal propulsion rates of small intestine in the DNCB gavages groups were
      significantly higher than that in the control group (P<0.01). The DAI scores and
      pathological score in DNCB enema groups were also higher than that in the control
      group (P<0.05), and there were significant rises in LMIF activity in DNCB enema
      groups as compared with control groups (P<0.01). CONCLUSION: Mouse
      gastrointestinal DTH reaction could be induced by DNCB, which might facilitate
      the mechanism underlying the ulcerative colitis.

PMID- 15259077
TI  - Hepatitis B virus X gene induces human telomerase reverse transcriptase mRNA
      expression in cultured normal human cholangiocytes.
AB  - AIM: To study the transcriptional regulation of human telomerase reverse
      transcriptase (hTERT) mRNA in normal human cholangiocytes (HBECs) after hepatitis
      B virus X (HBx) gene transfection and to elucidate the possible mechanism of HBV
      infection underlying cholangiocarcinoma. METHODS: HBECs were cultured in vitro
      and co-transfected with a eukaryotic expression vector containing the HBx coding
      region and a cloning vector containing coding sequences of enhanced green
      fluorescent protein (EGFP) using lipid-mediated gene transfer. The transfection
      efficiency was determined by the expression of EGFP. The expressions of hTERT
      mRNA and HBx protein in HBECs were detected by RT-PCR and immunocytochemical
      stain, respectively. RESULTS: The transfection efficiencies were about 15% for
      both HBx gene expression plasmid and empty vector. No hTERT mRNA was expressed in
      HBECs when transfected with OPTI-MEM medium and empty vector, but a dramatic
      increase was observed for hTERT mRNA expression in HBECs when transfected with
      HBx expression vector. HBx protein was only expressed in HBECs when transfected
      with HBx expression vector. CONCLUSION: HBx transfection can activate the
      transcriptional expression of hTERT mRNA. Cis-activation of hTERT mRNA by HBx
      gene is the primary mechanism underlying the proliferation, differentiation and
      tumorigenesis of biliary epithelia.

PMID- 15259078
TI  - In vitro anti-coxsackievirus B(3) effect of ethyl acetate extract of Tian-hua
      fen.
AB  - AIM: To investigation the anti-coxsackievirus B(3) (CVB(3m)) effect of the ethyl
      acetate extract of Tian-hua-fen on HeLa cells infected with CVB(3m). METHODS:
      HeLa cells were infected with CVB(3m) and the cytopathic effects (CPE) were
      observed through light microscope and crystal violet staining on 96-well plate
      and A(600) was detected using spectrophotometer. The protective effect of the
      extract to HeLa cells and the mechanism of the effect were also evaluated through
      the change of CPE and value of A(600). RESULTS: The extract had some toxicity to
      HeLa cells at a higher concentration while had a marked inhibitory effect on cell
      pathological changes at a lower concentration. Consistent results were got
      through these two methods. We also investigated the mechanism of its anti-CVB(3m)
      effect and the results indicated that the extract represented an inhibitory
      effect through all the processes of CVB(3m) attachment, entry, biosynthesis and
      assemble in cells. CONCLUSION: The results demonstrate that the ethyl acetate
      extract of Tian-hua-fen has a significant protective effect on HeLa cells
      infected with CVB(3m) in a dose-dependent manner and this effect exists through
      the process of CVB(3m) attachment, entry, biosynthesis and assemble in cells,
      suggesting that the ethyl acetate extract of Tian-hua-fen can be developed as an
      anti-virus agent.

PMID- 15259080
TI  - Therapeutic plasma exchange in patients with hyperlipidemic pancreatitis.
AB  - AIM: To clarify the effectiveness of plasma exchange by comparing the mortality
      and morbidity before and after the intervention of plasma exchange. METHODS:
      Plasma exchange has been available as an optional therapy for hyperlipidemic
      pancreatitis since August 1999 in our hospital. The patients were assorted into 2
      groups (group I: before August 1999 and group II: after August 1999). Group I
      consisted of 34 patients (before the availability of plasma exchange). Group II
      consisted of 60 patients (after the availability of plasma exchange). Twenty
      patients in group II received plasma exchange after giving their consent. The
      mortality and morbidity were compared between group I and group II. Furthermore,
      the patients with severe hyperlipidemic pancreatitis (Ranson's score > or = 3)
      were analyzed separately. The mortality and morbidity were also compared between
      those receiving plasma exchange (group A) and those who did not receive plasma
      exchange (group B). RESULTS: There was no statistical difference in the
      mortality, systemic and local complications between group I and group II. When
      the patients with severe hyperlipidemic pancreatitis were analyzed separately,
      there was no statistical difference between group A and group B. CONCLUSION:
      Plasma exchange can not ameliorate the overall mortality or morbidity of
      hyperlipidemic pancreatitis. The time of plasma exchange might be the critical
      point. If patients with hyperlipidemic pancreatitis can receive plasma exchange
      as soon as possible, better result may be predicted. Further study with more
      cases is needed to clarify the role of plasma exchange in the treatment of
      hyperlipidemic pancreatitis.

PMID- 15259079
TI  - FR167653 attenuates murine immunological liver injury.
AB  - AIM: To study the effect of FR167653 on immunological liver injury (ILI) in mice.
      METHODS: ILI was established by tail vein injection of 2.5 mg Bacillus Calmette
      Guerin (BCG), and 10 d later with 10 mg lipopolysaccharide (LPS) in 0.2 mL saline
      (BCG plus LPS). Alanine aminotransferase (ALT), aspartate aminotransferase (AST)
      in sera and malondialdehyde (MDA), glutathione peroxidase (GSHpx) contents in
      liver homogenates were assayed by spectrophotometry. The levels of tumor necrosis
      factor-alpha (TNF-alpha) and nitric oxide (NO) levels in sera were determined
      using ELISA. Interleukin-1 (IL-1) produced by peritoneal macrophages was
      determined by the method of (3)H-infiltrated cell proliferation. The nuclear
      factor-kappa B (NF-kappaB) p65 in liver tissue was analyzed with reverse
      transcription polymerase chain reaction (RT-PCR). Liver samples collected were
      stained with hematoxylin and eosin. RESULTS: FR167653 (50, 100, 150 mg/kg) could
      significantly decrease the serum transaminase (ALT, AST) activity and MDA content
      in liver homogenate, and improve reduced GSHpx level of liver homogenate. Liver
      histopathological examination showed FR167653 (100, 150 mg/kg) significantly
      reduced inflammatory cells infiltration and liver cells necrosis. FR167653 (50,
      100, 150 mg/kg) significantly lowered TNF-alpha and NO levels in serum, and IL-1
      produced by peritoneal macrophages. Moreover, expression of NF-kappaB mRNA in
      liver tissue of ILI induced by BCG plus LPS was significantly reduced by
      FR167653. CONCLUSION: All results showed that FR167653 had significant inhibitory
      action on ILI in mice.

PMID- 15259081
TI  - Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide
      following acute necrotizing experimental pancreatitis.
AB  - AIM: In previous experiments we have demonstrated that by administering low doses
      of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L
      arginine (Arg)-induced pancreatitis is accelerated. In rats that were also
      diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not
      observed. The aim of this study was to deduce whether the administration of
      exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in
      diabetic-pancreatitic rats. METHODS: Male Wistar rats were used for the
      experiments. Diabetes mellitus was induced by administering 60 mg/kg body mass of
      STZ intraperitoneally (i.p.), then, on d 8, pancreatitis was induced by 200
      mg/100 g body mass Arg i.p. twice at an interval of 1 h. The animals were
      injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 ?g/kg of CCK-8
      and/or 2 IU mixed insulin (300 g/L short-action and 700 g/L intermediate-action
      insulin) for 14 d after pancreatitis induction. Following this the animals were
      killed and the serum amylase, glucose and insulin levels as well as the plasma
      glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic
      contents of DNA, protein, amylase, lipase and trypsinogen were measured.
      Pancreatic tissue samples were examined by light microscopy on paraffin-embedded
      sections. RESULTS: In the diabetic-pancreatitic rats treatment with insulin and
      CCK-8 significantly elevated pw/bm and the pancreatic contents of protein,
      amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered
      in combination with insulin also elevated the number of acinar cells with mitotic
      activities, whereas CCK-8 alone had no effect on laboratory parameters or the
      mitotic activities in diabetic-pancreatitic rats. CONCLUSION: Despite the
      hypertrophic effect of CCK-8 being absent following acute pancreatitis in
      diabetic-rats, the simultaneous administration of exogenous insulin restored this
      effect. Our results clearly demonstrate that insulin is necessary for the
      hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.

PMID- 15259082
TI  - Effects of terlipressin on systolic pulmonary artery pressure of patients with
      liver cirrhosis: an echocardiographic assessment.
AB  - AIM: Portopulmonary hypertension is a serious complication of chronic liver
      disease. Our aim was to search into the effect of terlipressin on systolic
      pulmonary artery pressure among cirrhotic patients. METHODS: Twelve patients (6
      males and 6 females) with liver cirrhosis were recruited in the study. Arterial
      blood gas samples were obtained in sitting position at rest. Contrast enhanced
      echocardiography and measurements of systolic pulmonary artery pressure were
      performed before and after the intravenous injection of 2 mg terlipressin.
      RESULTS: Of 12 patients studied, the contrast enhanced echocardiography was
      positive in 5, and the positive findings in contrast enhanced echocardiography
      were reversed to normal in two after terlipressin injection. The mean systolic
      pulmonary artery pressure was 25.5+/-3.6 mmHg before terlipressin injection, and
      was 22.5+/-2.5 mmHg after terlipressin (P=0.003). The systolic pulmonary artery
      pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin
      injection, systolic pulmonary artery pressure was <25 mmHg in four of these cases
      (58.3% vs 25%, P=0.04). CONCLUSION: Terlipressin can decrease the systolic
      pulmonary artery pressure in patients with liver cirrhosis.

PMID- 15259083
TI  - Empirical antibiotic treatment with piperacillin-tazobactam in patients with
      microbiologically-documented biliary tract infections.
AB  - AIM: To report our experience with empiric antimicrobial monotherapy
      (piperacillin/tazobactam, of which no data are available in such specific
      circumstances) in microbiologically-documented infections in patients with benign
      and malignant conditions of the biliary tract. METHODS: Twenty-three patients, 10
      with benign and 13 with malignant conditions affecting the biliary tree and
      microbiologically-documented infections were recruited and the efficacy of
      empirical antibiotic therapy was assessed. RESULTS: The two groups featured
      similar demographic and clinical data. Overall, the infective episodes were most
      due to Gram negative agents, more than 60% of such episodes (mostly in malignant
      conditions) were preceded by invasive instrumental maneuvers. Empirical
      antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in
      more than 80% of cases. No deaths were reported following infections. CONCLUSION:
      An empiric therapeutic approach with piperacillin/tazobactam is highly effective
      in biliary tract infections due to benign or malignant conditions.

PMID- 15259084
TI  - Determination of glycated hemoglobin in patients with advanced liver disease.
AB  - AIM: To evaluate the glycated hemoglobin (HbA(1c)) determination methods and to
      determine fructosamine in patients with chronic hepatitis, compensated cirrhosis
      and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA(1c)
      values were determined in 15 patients with compensated liver cirrhosis and in 20
      patients with chronic hepatitis using the ion-exchange high performance liquid
      chromatography and the immunoassay methods. Fructosamine was determined using
      nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis
      had HbA(1c) results below the non-diabetic reference range by at least one
      HbA(1c) method, while fructosamine results were either within the reference range
      or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis)
      had HbA(1c) results below the non-diabetic reference range by at least one
      HbA(1c) method. In patients with chronic hepatitis treated with ribavirin, 50% of
      HbA(1c) results were below the non-diabetic reference using at least one of the
      HbA(1c) methods. CONCLUSION: Only evaluated in context with all liver function
      parameters as well as a red blood count including reticulocytes, HbA(1c) results
      should be used in patients with advanced liver disease. HbA(1c) and fructosamine
      measurements should be used with caution when evaluating long-term glucose
      control in patients with hepatic cirrhosis or in patients with chronic hepatitis
      and ribavirin treatment.

PMID- 15259085
TI  - Expression and localization of c-Fos and NOS in the central nerve system
      following esophageal acid stimulation in rats.
AB  - AIM: To determine the distribution of neurons expressing c-Fos and nitric oxide
      synthase (NOS) in the central nerve system (CNS) following esophageal acid
      exposure, and to investigate the relationship between c-Fos and NOS. METHODS:
      Twelve Wistar rats were randomly divided into two equal groups. Hydrochloric acid
      with pepsin was perfused in the lower part of the esophagus for 60 min. As a
      control, normal saline was used. Thirty minutes after the perfusion, the rats
      were killed and brains were removed and processed for c-Fos immunohistochemistry
      and NADPH-d histochemistry. Blood pressure (BP), heart rate (HR), and respiratory
      rate (RR) during the experimental procedures were recorded every 10 min. RESULTS:
      There were no significant differences in BP, HR and RR between the two groups. c
      Fos immunoreactivity was significantly increased in rats receiving acid plus
      pepsin perfusion in amygdala (AM), paraventricular nucleus (PVN), parabrachial
      nucleus (PBN), nucleus tractus solitarius and dorsal motor nucleus of vagus
      (NTS/DMV), nucleus ambiguous (NA), reticular nucleus of medulla (RNM) and area
      postrema (AP). NOS reactivity in this group was significantly increased in PVN,
      PBN, NTS/DMV, RNM and AP. c-Fos and NOS had significant correlation between PVN,
      PBN, NTS/DMV, RNM and AP. CONCLUSION: Acid plus pepsin perfusion of the esophagus
      results in neural activation in areas of CNS, and NO is likely one of the
      neurotransmitters in some of these areas.

PMID- 15259086
TI  - Effect of octreotide on human pancreatic cancer cells after transfected with
      somatostatin receptor type 2 gene.
AB  - AIM: To observe the effect of octreotide on apoptosis rate of human pancreatic
      cancer cells PC-3 after transfected with somatostatin receptor type 2 (SST2)
      gene. METHODS: SST2 plasmid was transfected into PC-3 cells by liposome. Result
      of transfection was detected by immunocytochemical staining and Western blotting.
      Apoptosis rates of PC-3 cells under different dosages of octreotide were measured
      by MTT assay and flow cytometry (FCM). RESULTS: Apoptosis rate caused by
      octreotide of transfected PC-3 cells was 7.56+/-1.06% at the dosage of 0.20
      microg/mL, 9.25+/-1.73% at the dosage of 0.40 microg/mL and 14.18+/-2.71% at the
      dosage of 0.80 microg/mL. Apoptosis rate caused by octreotide of non-transfected
      PC-3 cells was 5.76+/-0.75% at the dosage of 0.20 microg/mL, 6.69+/-0.80% at the
      dosage of 0.40 microg/mL and 7.26+/-1.28% at the dosage of 0.80 microg/mL.
      Transfected PC-3 cells growth inhibition rate caused by octreotide was 9.36+/
      1.34% at the dosage of 0.20 microg/mL, 12.03+/-1.44% at the dosage of 0.40
      microg/mL and 20.23+/-4.21% at the dosage of 0.80 microg/mL. Non-transfected PC-3
      cells growth inhibition rate caused by octreotide was 6.44+/-0.66% at the dosage
      of 0.20 microg/mL, 7.65+/-0.88% at the dosage of 0.40 microg/mL and 9.29+/-1.32%
      at the dosage of 0.80 microg/mL. We found that octreotide caused higher apoptosis
      rate and inhibition rate in transfected groups than in non-transfected groups
      (P<0.05) at the tested dosages (0.20, 0.40 and 0.80 microg/mL). CONCLUSION:
      Deficiency of SST2 was probably the major reason why octreotide had little effect
      on PC-3 cells. Transfecting SST2 gene could strengthen the ability of octreotide
      of killing PC-3 cells. It provided an experimental evidence for using both
      octreotide and transfection with SST2 gene on clinical treatment of pancreatic
      cancer.

PMID- 15259087
TI  - Inhibitory effect of Huangqi Zhechong decoction on liver fibrosis in rat.
AB  - AIM: To assess the inhibitory effect of Huangqi Zhechong decoction on hepatic
      fibrosis in rats induced by CCl(4) plus alcohol and high fat low protein diet.
      METHODS: Male SD rats were randomly divided into hepatic fibrosis model group,
      control group and 3 treatment groups consisting of 12 rats in each group. Except
      for the normal control group, all the rats were subcutaneously injected with
      CCl(4) at a dosage of 3 mL/kg. In 3 treated groups, either high-dose group (9
      mL/kg), or medium-dose group (6 mL/kg), or low-dose group (3 mL/kg) was daily
      gavaged with Huangqi Zhechong decoction, and saline vehicle was given to model
      and normal control rats. Enzyme-linked immunosorbent assay (ELISA) and
      biochemical examinations were used to determine the changes of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA),
      laminin (LN), type-III-procollagen-N-peptide (PIIIP), and type IV collagen
      content in serum, and hydroxyproline (Hyp) content in liver after sacrificing the
      rats. Pathologic changes, particularly fibrosis were examined by hematoxylin and
      eosin (HE) and Van Gieson staining. RESULTS: Compared with the model control
      group, serum ALT, AST, HA, LN, PIIIP and type IV collagen levels dropped markedly
      in Huangqi Zhechong decoction groups, especially in the medium-dose Huangqi
      Zhechong decoction group (1 954+/-576 U/L vs 759+/-380 U/L, 2 735+/-786 U/L vs 1
      259+/-829 U/L, 42.74+/-7.04 ng/mL vs 20.68+/-5.85 ng/mL, 31.62+/-5.84 ng/mL vs
      14.87+/-1.45 ng/mL, 3.26+/-0.69 ng/mL vs 1.47+/-0.46 ng/mL, 77.68+/-20.23 ng/mL
      vs 25.64+/-4.68 ng/mL, respectively) (P<0.05). The Hyp content in liver tissue
      was also markedly decreased (26.47+/-11.24 mg/mgprot vs 9.89+/-3.74 mg/mgprot)
      (P<0.01). Moreover, the stage of the rat liver fibrosis in Huangqi Zhechong
      decoction groups was lower than that in model group, and more dramatic drop was
      observed in medium-dose Huangqi Zhechong decoction group (P<0.01). CONCLUSION:
      Huangqi Zhechong decoction can inhibit hepatic fibrosis resulted from chronic
      liver injure, retard the development of cirrhosis, and notably ameliorate the
      liver function. It may be a safe and effective therapeutic drug for patients with
      fibrosis.

PMID- 15259088
TI  - Transanal approach in repairing acquired rectovestibular fistula in females.
AB  - AIM: To summarize the operative experience of the transanal approach in acquired
      rectovestibular fistula repair. METHODS: Ninety-six cases of acquired
      rectovestibular fistula in young females were analyzed retrospectively. The
      etiology and operative procedure were discussed. Operative essential points were,
      the patient was laid in prone frog position, with the knees and hips flexed at
      90(o); the perineum was elevated; and the anal opening was exposed. Four stay
      sutures were applied to the margin of the fistular orifice in the anal opening at
      points 3, 6, 9 and 12 o'clock. A circular incision of mucosa surrounding the stay
      sutures was made. The fistula was dissected from its anal opening to its
      vestibular opening. The wound of vestibule was sutured, and the rectoanal wound
      was then sutured transversely. RESULTS: All the 96 patients recovered
      uneventfully from operation with a successful rate of 93.75%. CONCLUSION: The
      transanal approach in the treatment of the acquired rectovestibular fistula is a
      simple and feasible technique.

PMID- 15259089
TI  - Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy.
AB  - A 62-year-old Japanese man who was positive for hepatitis B surface antigen
      (HBsAg) and anti-HBe antibody, underwent chemotherapy for non-Hodgkin's lymphoma
      (NHL). Mutations were detected in the precore region (nt1896) of HBV. Because
      steroid-containing regimen may cause reactivation of hepatitis B virus (HBV) and
      hepatitis may progress to be fulminant after its withdrawal, we administered CHO
      (CPA, DOX and VCR) therapy and the patient obtained complete response. However,
      he developed acute exacerbation of hepatitis due to HBV reactivation. Recovery
      was achieved with lamivudine (100 mg/d) and plasma exchange. The present case
      suggests that acute exacerbation of hepatitis can occur with steroid-free
      regimen. Because the efficacy of the prophylactic use of lamivudine has been
      reported and the steroid enhances curability of malignant lymphoma, the steroid
      containing regimen with prophylaxis of lamivudine should be evaluated further.

PMID- 15259090
TI  - Alverine citrate induced acute hepatitis.
AB  - Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE
      search on January 2004 revealed only 1 report implicating the hepatotoxicity of
      this agent. A 34-year-old woman was investigated because of the finding of
      elevated liver function tests on biochemical screening. Other etiologies of
      hepatitis were appropriately ruled out and elevated enzymes were ascribed to
      alverine citrate treatment. Although alverine citrate hepatotoxicity was related
      to an immune mechanism in the first case, several features such as absence of
      predictable dose-dependent toxicity of alverine citrate in a previous study and
      absence of hypersensitivity manifestations in our patient are suggestive of a
      metabolic type of idiosyncratic toxicity.

PMID- 15259092
TI  - [Informing the child and his/her family].

PMID- 15259091
TI  - Pregnant woman with fulminant hepatic failure caused by hepatitis B virus
      infection: a case report.
AB  - AIM: To report the experience in successfully treating pregnant women with severe
      hepatitis. METHODS: Comprehensive medical treatments were performed under strict
      monitoring. RESULTS: Pregnant woman with severe hepatitis was successfully
      rescued. CONCLUSION: Vital measures taken in the treatment of pregnant women with
      severe hepatitis include termination of the pregnancy at a proper time and
      control of various complications, such as disseminated intravascular coagulation
      (DIC), hepatorenal syndrome, hepatic encephalopathy and infection.

PMID- 15259093
TI  - [The medical information of parents: a philosophic viewpoint].

PMID- 15259094
TI  - [The medical information: a psychanalytic viewpoint].

PMID- 15259095
TI  - [Informing the child and his/her family: legal aspects].

PMID- 15259096
TI  - [Information and ambulatory pediatrics: for an ethical reflexion].

PMID- 15259097
TI  - [Informing patients and families about genetic renal diseases].

PMID- 15259098
TI  - [Child's and parents' information: their experience].

PMID- 15259099
TI  - [Personal child health record: informativity and confidentiality].

PMID- 15259100
TI  - [Confidentiality and school].

PMID- 15259101
TI  - [Ethics and pediatrics: the media].

PMID- 15259102
TI  - [Informing the child and his/her family].

PMID- 15259103
TI  - [Chronic viral hepatitis C].

PMID- 15259104
TI  - [Osteoclastic giant cell tumor of the pancreas. A rare pancreatic variant of
      neoplasia].

PMID- 15259105
TI  - [Gastric metastatis due to Merkel cell carcinoma: a rare cause of gastric
      bleeding].

PMID- 15259106
TI  - A potential role for beta-carotene in avian embryonic development.
AB  - Vitamin A is essential for vertebrate embryonic development; dietary carotenoids
      are the primary source of vitamin A since animals cannot synthesize it de novo.
      To study the role of beta-carotene during embryonic development, we analyzed in
      chick embryos the expression of beta,beta-carotene 15,15'-oxygenase (beta-oxy)
      which cleaves beta-carotene to produce two molecules of retinal. Beta-oxy
      transcripts were detected in one-and-a-half- to five-day-old embryo homogenates
      and in situ hybridization in five-day-old embryos, revealing their presence in
      tissues including the central nervous system, lungs, limbs, and cardiovascular
      system. Moreover, we detected beta-oxy enzymatic activity in extracts from five
      day-old embryos as well as small amounts of beta-carotene in the egg yolk. These
      results indicate that beta-oxy is present during early developmental stages,
      raising the possibility that yolk-stored beta-carotene is utilized as a source of
      vitamin A. Thus, our results suggest that beta-carotene could play an important
      role in early avian embryonic development as a local source of vitamin A in
      specific tissues.

PMID- 15259107
TI  - WHO pushing to rapidly scale-up TB/HIV programmes.

PMID- 15259114
TI  - Diagnosis and management if insulinomas.

PMID- 15259115
TI  - Evidenced-based medicine: weakness revealed.

PMID- 15259116
TI  - Evidence-based medicine: "It depends".

PMID- 15259118
TI  - Evidence-based medicine: common sense discarded.

PMID- 15259117
TI  - Evidence-based medicine: a fallacious concept.

PMID- 15259119
TI  - Visual vignette. Somatostatin receptor scintigraphy.

PMID- 15259120
TI  - Undertreatment of osteoporosis in residents of nursing homes: population-based
      study with use of the Systematic Assessment of Geriatric Drug Use via
      Epidemiology (SAGE) database.
AB  - OBJECTIVE: To determine the proportion of nursing home residents >65 years of age
      with osteoporosis who were receiving antiosteoporosis pharmacotherapy and to
      identify the predictors of administration of such drugs. METHODS: We identified
      29,357 patients with osteoporosis documented on the Minimum Data Set collected on
      residents of all nursing home facilities in 5 states during the period from 1992
      through 1996. A multiple logistic regression model was used for analysis, with
      the dependent variable being use of any antiosteoporosis drug. RESULTS: Among the
      nursing home residents with osteoporosis, 25% received antiosteoporosis drugs.
      Women were more likely than men to receive antiosteoporosis drugs (adjusted odds
      ratio [OR], 1.41; 95% confidence interval [CI], 1.26 to 1.57). Both increasing
      age and level of cognitive impairment were inversely related to receipt of
      antiosteoporosis drugs. A history of fracture or falls was not predictive of use
      of such drugs. Treatment was less likely for nursing home residents with > or = 6
      medical conditions (OR 0.55, 95% CI 0.51 to 0.59); those admitted to a nursing
      home from a hospital (OR 0.86, 95% Cl 0.80 to 0.92); and those with a terminal
      prognosis (OR 0.60,95% CI 0.42 to 0.87). CONCLUSION: The majority of nursing home
      residents with osteoporosis in this study did not receive drug therapy for this
      disabling and treatable disease. Although acceptable reasons may exist in some of
      these residents,others--especially the oldest old--may not be receiving adequate
      care.

PMID- 15259121
TI  - Thyrotoxic hypokalemic periodic paralysis in a Native American patient: case
      report and literature review.
AB  - OBJECTIVE: To describe a rare case of thyrotoxic hypokalemic periodic paralysis
      in a half Native American and half African American person. METHODS: We present a
      case of a man of Native American descent with thyrotoxic periodic paralysis and
      review the pertinent literature. RESULTS: In a 53-year-old man with untreated
      hyperthyroidism, bilateral lower extremity weakness developed as a result of
      hypokalemia. Two months before admission, the patient had thyroid function test
      results that were consistent with hyperthyroidism. He also had undergone a
      thyroid radioiodine uptake study and scan, which demonstrated a diffuse 60%
      uptake in the thyroid at 24 hours. His symptoms resolved promptly after treatment
      with potassium, a 3-adrenergic blocking agent, and propylthiouracil. The
      pathophysiologic features of this disorder have not been entirely elucidated but
      most likely involve a sudden increase in intracellular shift of potassium and
      progressive depolarization of the resting membrane potential. Therapy consists of
      replacing the potassium and treating the cause. CONCLUSION: Thyrotoxic
      hypokalemic periodic paralysis, although rare in the Native American and African
      American population, should be considered in the differential diagnosis of
      hypokalemia and flaccid paralysis. Timely recognition and prompt treatment can
      reduce the risk of severe morbidity.

PMID- 15259122
TI  - Artificially low hemoglobin A1c caused by use of dapsone.
AB  - OBJECTIVE: To describe a case of artifactually decreased hemoglobin Alc (HbAlc)
      attributable to use of dapsone. METHODS: We present a detailed case report and
      results of a related literature search. In addition, potential causes of
      artifactually lowered HbAlc values are discussed. RESULTS: A 35-year-old patient
      with type I diabetes had high home-monitored blood glucose values, high clinic
      plasma glucose determinations, increased fructosamine levels, and low HbAlc
      values. The lowering of the HbAlc level was associated with use of dapsone, and
      the decrease in HbAlc value was proportional to the dose of dapsone. A literature
      search revealed one previous report of artifactual lowering of the HbAlc value,
      in which high methemoglobin levels were found and thought to be the cause of the
      artifactually decreased HbA1c. CONCLUSION: By increasing methemoglobin levels and
      decreasing erythrocyte survival, dapsone can artifactually lower HbA1c.
      Clinicians should be aware of this potential side effect of dapsone.

PMID- 15259123
TI  - Lichen amyloidosus and chronic urticaria.

PMID- 15259124
TI  - Endocrine-related resources fron the National Institutes of Health.

PMID- 15259125
TI  - National Hormone and Peptide Program (NHPP): new recombinant hormones,
      hypothalamic peptides, natural hormones, new antisera, and expanded hormone assay
      services available.

PMID- 15259126
TI  - Patient information from the Hormone Foundation. Osteoporosis and women's health.

PMID- 15259127
TI  - Abstracts of the Euroconference Angiogenesis II. June 19-20, 2003. Paris, France.

PMID- 15259138
TI  - Gastric carcinogenesis.

PMID- 15259140
TI  - Pseudopancreatitis and choledochal cyst.

PMID- 15259143
TI  - Intestinal obstruction by eosinophilic jejunitis.
AB  - Eosinophilic enteritis is an uncommon disease that rarely develops as a surgical
      emergency. Although it may be associated with infestation by Ancylostoma caninum,
      its etiology is unknown and often related to a personal or family history of
      atopy. A transmural involvement may cause intestinal obstruction--more frequently
      in the jejunum--or even acute abdomen, which may or may not be accompanied by
      intestinal perforation. The latter two conditions tend to be more commonly
      associated with ileum disease, causing pain in the lower right quadrant of the
      abdomen. Patient history, eosinophil count--which may be paradoxically reduced
      when the disease appears in this way--, ultrasonography, and/or CT lead to the
      suspicion of this condition before a surgical procedure is considered. A
      definitive diagnosis, however, must be reached by means of an anatomopathological
      study. Macroscopically, intestinal loops exhibit a thickened appearance with an
      elastic consistency. Laparoscopic intestinal biopsy may play a major role in the
      diagnosis of disease.

PMID- 15259145
TI  - [Patient information. Traveller's diarrhea].

PMID- 15259147
TI  - Influencing prescribing habits?

PMID- 15259146
TI  - Images in emergency medicine. Cutaneous Anthrax.

PMID- 15259148
TI  - [Papillary cystic solid tumor of the pancreas. Three different ways of
      presentation].

PMID- 15259149
TI  - Severe hypercapnia caused by acute heroin overdose.

PMID- 15259150
TI  - Building evidence for early initiation of clopidogrel loading in non-ST-segment
      elevation acute coronary syndromes: going past the American College of
      Cardiology/American Heart Association guidelines.

PMID- 15259152
TI  - [Spanish language].

PMID- 15259151
TI  - [Primary leiomyosarcoma of the gallbladder].

PMID- 15259153
TI  - Emergency physicians in the military: a sequel.

PMID- 15259154
TI  - What military emergency physicians really do.

PMID- 15259155
TI  - Military emergency medicine.

PMID- 15259156
TI  - Emergency physicians in the United States Military.

PMID- 15259158
TI  - Appropriate interhospital patient transfer.

PMID- 15259157
TI  - Endovascular repair of abdominal aortic aneurysm in a kidney transplant patient
      with 4-year follow-up.

PMID- 15259159
TI  - Code of ethics for emergency physicians.

PMID- 15259160
TI  - Legal sanctions and rehabilitation for driving under the influence.

PMID- 15259161
TI  - Anaphylaxis after Rattlesnake bite.

PMID- 15259162
TI  - Boerhaave's syndrome in a healthy adolescent male presenting with
      pneumomediastinum.

PMID- 15259163
TI  - Tricyclic antidepressant treatment ambiguities.

PMID- 15259164
TI  - The smallpox vaccine and coronary artery disease: a personal perspective.

PMID- 15259165
TI  - When is zero zero?

PMID- 15259166
TI  - Physical examination can exclude clinically important cervical spine injury.

PMID- 15259167
TI  - Picking a winner among decision aids.

PMID- 15259168
TI  - Fluoroquinolones should be avoided in myasthenia gravis.

PMID- 15259169
TI  - Fracture of the delicate bamboo: a diagnostic pitfall.

PMID- 15259170
TI  - Acute multiple thrombosis as early presentation of lung cancer.

PMID- 15259171
TI  - Decision rules for computed tomographic scans in children after head trauma.

PMID- 15259173
TI  - The Combitube as rescue device: recommended use of the small adult size for all
      patients six feet tall or shorter.

PMID- 15259174
TI  - Facing an outbreak of highly transmissible disease: problems in emergency
      department response.

PMID- 15259175
TI  - Peripheral arterial disease.

PMID- 15259176
TI  - Neck pain.

PMID- 15259177
TI  - Erectile dysfunction.

PMID- 15259178
TI  - Tough trade-offs: medical bills, family finances and access to care.
AB  - About 20 million American families-representing 43 million people-reported
      problems paying medical bills in 2003, according to a new study by the Center for
      Studying Health System Change (HSC). While uninsured families are more likely to
      have medical bill problems, two-thirds of families with problems paying medical
      bills have health insurance coverage. Of all families with medical bill problems,
      almost two-thirds reported difficulty paying for other basic necessities-rent,
      mortgage payments, transportation or food-as a result of medical debt. People in
      families with medical bill problems also reported much greater trouble getting
      care because of cost concerns-one in three did not get a prescription drug, one
      in four delayed care and one in eight went without needed care.

PMID- 15259179
TI  - Images in emergency medicine. Secondary syphilis with Jarisch-Herxheimer
      reaction.

PMID- 15259181
TI  - I don't want to hear about the "standard of care".

PMID- 15259180
TI  - Frequent attenders to an accident and emergency department.

PMID- 15259182
TI  - Droperidol and the black box warning.

PMID- 15259183
TI  - Out-of-hospital rescue oxygenation and tracheal intubation with the intubating
      laryngeal mask airway in a morbidly obese patient.

PMID- 15259184
TI  - Lies, damned lies, and statistics...

PMID- 15259185
TI  - Change of shift. An emergency department lullaby.

PMID- 15259186
TI  - Change of shift. Checking my pulse.

PMID- 15259187
TI  - Change of shift. Four score and seven years.

PMID- 15259188
TI  - Change of shift. Cardiovert me, I have marathons to run.

PMID- 15259189
TI  - Literature watch.

PMID- 15259190
TI  - Global biotech expansion taking cues from Bayh-Dole.

PMID- 15259191
TI  - Navigating US conflict-of-interest rules when commercializing research.

PMID- 15259192
TI  - Do the social sciences create phenomena?: the example of public opinion research.
AB  - This paper is an investigation into the philosophy and the history of the social
      sciences. Some philosophers of the social sciences have suggested that a key
      feature of the natural sciences is their capacity to create phenomena, and that
      the social sciences do not meet this criterion. We suggest, to the contrary, that
      the social sciences can and do create phenomena, in the sense of new ways of
      describing and acting that have been used to produce all sorts of effects. Like
      the natural sciences, the social sciences create their phenomena through the
      procedures that are established to discover them. But the creation of phenomena
      is a complex, technically difficult and contested process and its success rare.
      Historically, this argument is developed through a case-study of the development
      and evolution of public opinion research in the USA and Britain. We argue that by
      the 1950s public opinion produced a version of the world that had entered 'into
      the true'. Special attention is given to technical considerations in the
      development of public opinion research, especially the genealogy of a particular
      research technology, that of the representative sample. Whilst we are not
      concerned with demarcation criteria, we argue that there are some important
      differences between the social and the natural sciences; that the former have a
      less concentrated 'spatial mix' and a slower 'tempo of creativity'. None the
      less, in this particular case, the social sciences have played a key role in the
      creation of opinioned persons and an opinionated society.

PMID- 15259193
TI  - Elite formation under occupation: the internal stratification of palestinian
      elites in the West Bank and Gaza Strip.
AB  - This paper examines the internal stratification of Palestinian elites in the West
      Bank and Gaza Strip under Israeli occupation. Our general aim is to clarify the
      extent to which social and political subordination to outside rule influences the
      development of indigenous elites in stateless societies. In contrast to nation
      state societies, such elites may be horizontally stratified into a wider range of
      institutional settings, and vertically stratified by anti-occupation activism
      alongside the attainment of occupational prestige. In addition, context-specific
      determinants of their stratification patterns, such as refugee status,
      regionality, and country in which educational credentials were acquired, should
      be considered. A secondary content analysis of interviews conducted by the
      Palestinian Panorama centre with 249 elite members reveals, that the vertical
      stratification of Palestinian elites along occupational attainment and anti
      occupation activism constitutes two quite independent status dimensions. A
      multinomial logit regression shows that, horizontally, elite groups are embedded
      in four distinct types of institutional activity, further demonstrating the multi
      faceted formation of Palestinian elites. Contextual resources, such as refugee
      versus non-refugee status, regionality, and the acquiring of Western credentials,
      have differential effects on the vertical and horizontal stratification of
      Palestinian elites. The implications of these findings for further research on
      elite formation in the post-Oslo Palestinian society and in other stateless
      societies are discussed in conclusion.

PMID- 15259194
TI  - Beyond the racist/hooligan couplet: race, social theory and football culture.
AB  - This paper draws on recent research to explore the changing cultures of racism in
      English football. Starting from a critical analysis of key themes in the
      literature on football it seeks to show that existing analytical frameworks need
      to be reworked if they are going to adequately account for the complex forms
      through which racism is expressed in contemporary football cultures. In the
      course of this analysis we question some of the ways in which the issue of racism
      in football is collapsed into broader accounts of 'hooliganism' and other forms
      of violence among football fans. From this starting point the paper draws on some
      elements of our empirical research in order to outline an alternative way of
      framing the issues of racism and multicultrralism in football.

PMID- 15259195
TI  - Repartnering: the relevance of parenthood and gender to cohabitation and
      remarriage among the formerly married.
AB  - This paper is an exploratory analysis of the impact of current and anticipated
      parenthood on cohabitation and remarriage among those formerly living in marriage
      type relationships. The focus on children is embedded within a broader analysis
      of repartnering which takes account of other factors, including gender.
      Quantitative and qualitative analyses are used, with a multivariate analysis of
      repartnering patterns, using data from the General Household Survey, being
      complemented by in-depth interview data examining the attitudes of the formerly
      married to future relationships. The paper demonstrates that parenthood has a
      statistically significant effect on the likelihood of formerly married women
      repartnering, with a higher number of children being associated with a lower
      probability of repartnering. The presence of children can work against
      repartnering in a variety of ways. Children place demands on their parents and
      can deter or object to potential partners. Parents may see their parental role as
      more important than, and a barrier to, new relationships. However, mothers are
      typically looking for partners for themselves rather than fathers for their
      children. Among formerly married people without children, the desire to become a
      parent encourages repartnering. The paper concludes that parenthood should be a
      key consideration in analyses of repartnering.

PMID- 15259196
TI  - Idealist thought, social policy and the rediscovery of informal care.
AB  - Recent work in the history of welfare has suggested a need to reconsider the
      status of some conceptual frameworks within sociology and social policy studies
      regarding the meaning of 'social welfare' and the 'welfare state'. In this
      context, the present article argues in particular that the marked upswing of
      interest in informal care in the UK beginning in the 1970s reflected, at least in
      part, a reaction, itself not so far adequately understood, to some features of
      the work of Richard Titmuss and 'traditional social administration', work which,
      on examination, reveals a distinctive 'idealist' core, unsympathetic to research
      into familial patterns of caring. Similarities with 'classic' British idealism,
      broadly defined, at the end of the nineteenth and beginning of the twentieth
      centuries are reviewed. This idealist thought emerges too as unresponsive to
      informal care, even though contemporary non-idealist thought had discussed it.
      The article concludes that the (unacknowledged) persistence and influence of
      idealist modes of social thought diverted attention away from informal care;
      informal care was in fact not 'discovered' in the 1970s, it was rediscovered as
      idealist preconceptions about the nature of 'real' welfare were discarded. The
      sense of 'discovery' reflected prevailing and dubious historigraphical
      interpretations of the meaning of 'social welfare' and the status of the
      ('classic') 'welfare state'.

PMID- 15259197
TI  - Who killed whom?: victimization and culpability in the social construction of
      murder.
AB  - Based on in-depth interviews with relatives of people convicted of murder, this
      article examines the ways in which everyday understandings of 'murder' are
      socially constructed, as revealed by the narratives of murderers' relatives. To
      this end, interviewees' explanations of the killings are analysed and a
      distinction is drawn between interviewees who understood the killings committed
      by their relatives as manslaughter and those who accepted the murder verdict. In
      defining the offences in this way, interviewee s identified the significance of
      victimization and culpability to understandings of interpersonal violence.
      Through the analysis of interview data, it is possible to examine the ways in
      which 'murder' is seen to have occurred only when particular criteria of
      victimization and culpability are met.

PMID- 15259198
TI  - Theorizing fear of crime: beyond the rational/irrational opposition.
AB  - Much has been written about the 'social problem' of fear of crime in the
      criminological and sociological literature in recent years. We would argue that
      thus far in this literature, however, there has been too much emphasis on the
      question 'How rational is people's fear of crime?', a question that largely
      reduces the complexity of the phenomenon and positions a 'biased' lay response
      against an 'expert' objective judgment. In this article, we review different
      epistemological perspectives that can be offered to understand in greater depth
      the fear of crime phenomenon. We place particular emphasis on those hermeneutic
      perspectives that go beyond the models of the rationalist, individualistic
      subject to exploring issues of symbolic representation, discourse and the micro -
      and macro-contexts in which fear of crime is experienced and given meaning. We
      also draw upon two case studies from our own empirical research into fear of
      crime, conducted with the intention of exploring the situated narratives,
      cultural representations and different levels of symbolic meaning that contribute
      to the dynamic constitution of fear.

PMID- 15259199
TI  - The norm and the text: Denzin and Lincoln's handbooks of qualitative method.
AB  - Qualitative methods have lately enjoyed enhanced legitimacy and are increasingly
      used in academic and applied social research. Yet the field is marked by
      controversy about virtually every key tenet of qualitative inquiry, from matters
      of epistemology to purely practical matters of relations with research subjects.
      Not only is the practice of qualitative research hotly contested, consensus is
      lacking about the purpose of qualitative research and whether it has a
      distinctive role to play relative to other approaches to the study of social
      phenomena. Against this context, the handbooks of qualitative method edited by
      Norman Denzin and Yvonna Lincoln represent a significant attempt to capture the
      breadth of contemporary approaches to qualitative method. The article examines
      key contributions from the handbooks, drawing on these to develop a view of
      qualitative method from a pragmatic, realist perspective. Among the issues
      considered are the significance of relativism, subjectivity, post-modernism and
      feminist method, the politicization of the purposes of qualitative research, the
      debate over criteria of validity, and the move to treat qualitative research as
      an entertainment rather than a scientific practice.

PMID- 15259200
TI  - "The visible skeleton series": the art of Laura Ferguson.
AB  - Laura Ferguson's The Visible Skeleton Series constitutes an artistic self
      representation of scoliosis. Ferguson employs high-tech medical imaging and
      innovative graphical techniques to suggest a novel view of her skeletal
      "deformity." This section presents introductions to the series by a historian of
      medicine and by the artist herself, and offers personal and professional
      reflections on the work from an orthopedic surgeon, a social worker with lived
      experience of cleft lip, and a retired pediatric forensic pathologist.

PMID- 15259201
TI  - A "small-world" network hypothesis for memory and dreams.

PMID- 15259202
TI  - Ethical pluralism without complementarity.
AB  - Grinnell, Bishop, and McCullough (2002) have proposed extending Bohr's notion of
      complementarity from the realm of quantum physics to that of bioethics, arguing
      that many ethical disputes cannot in principle be resolved. On this view, we
      should give up the aim of reaching all-things-considered moral verdicts on a
      variety of disputed questions, settling instead for a holism of irreducibly
      complementary perspectives. I discuss a number of difficulties with this
      proposal, and argue that the desire for inclusiveness that motivates it is
      properly captured through a different approach to ethical pluralism already
      familiar in moral philosophy, which does allow for resolution.

PMID- 15259203
TI  - Hitler's penicillin.
AB  - During the Second World War, the Germans and their Axis partners could only
      produce relatively small amounts of penicillin, certainly never enough to meet
      their military needs; as a result, they had to rely upon the far less effective
      sulfonamides. One physician who put penicillin to effective use was Hitler's
      doctor, Theodore Morell. Morell treated the Fuhrer with penicillin on a number of
      occasions, most notably following the failed assassination attempt in July 1944.
      Some of this penicillin appears to have been captured from, or inadvertently
      supplied by, the Allies, raising the intriguing possibility that Allied
      penicillin saved Hitler's life.

PMID- 15259204
TI  - Therapy with saffron and the goddess at Thera.
AB  - This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100
      BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus
      carturightianus and its active principle, saffron, are the primary subjects at
      Xeste 3. Several lines of evidence suggest that the meaning of these frescoes
      concerns saffron and healing: (1) the unusual degree of visual attention given to
      the crocus, including the variety of methods for display of the stigmas; (2) the
      painted depiction of the line of saffron production from plucking blooms to the
      collection of stigmas; and (3) the sheer number (ninety) of medical indications
      for which saffron has been used from the Bronze Age to the present. The Xeste 3
      frescoes appear to portray a divinity of healing associated with her
      phytotherapy, saffron. Cultural and commercial interconnections between the
      Therans, the Aegean world, and their neighboring civilizations in the early 2nd
      millennium BCE indicate a close network of thematic exchange, but there is no
      evidence that Akrotiri borrowed any of these medicinal (or iconographic)
      representations. The complex production line, the monumental illustration of a
      goddess of medicine with her saffron attribute, and this earliest botanically
      accurate image of an herbal medication are all Theran innovations.

PMID- 15259205
TI  - Vignettes from psychiatric training, 1945-1951.

PMID- 15259206
TI  - Skepticism, statistical methods, and the cigarette: a historical analysis of a
      methodological debate.
AB  - The discipline of modern "risk factor" epidemiology was in its formative stages
      in the early 1950s, when epidemiologic studies revealed a strong association
      between cigarette smoking and lung cancer mortality. Many medical scientists and
      physicians were reluctant to accept these studies as a demonstration of causation
      because the methods were "statistical" and involved data collected in
      uncontrolled conditions outside the laboratory. But a substantial number of
      senior biostatisticians and epidemiologists also voiced concerns, albeit more
      methodologically sophisticated, about the quality of the evidence at the time.
      Statistical methods were just beginning to work their way into medicine and
      public health, and many epidemiologists and statisticians were concerned about
      the potential misuse of these methods by untrained investigators. When studies of
      smoking and lung cancer gained increasing publicity and were being used to
      recommend public health policies, some prominent epidemiologists and
      statisticians highlighted this debate in their efforts to pursue methodological
      reform. Participants in the debate over smoking and lung cancer saw the need for
      explicit and rigorous standards for evaluating etiologic hypotheses, but they
      held conflicting views about what those standards should be. These diverging
      views reflect an underlying tension within the discipline of epidemiology between
      the search for "objective" methods of scientific inference and the practical
      needs of public health research that persists today.

PMID- 15259207
TI  - Establishing the mental health baseline.
AB  - This paper introduces a new organization, cognitive-web.org, whose goal is to
      make cognitive tests available on the internet, and thereby to provide users with
      a "mental health baseline" against which to assess their cognitive function over
      time. These tests will provide information about changes in cognitive function
      during normal aging and in dementia.

PMID- 15259208
TI  - The meaning of natural childbirth.
AB  - The term "natural childbirth" encompasses a variety of methods, including the
      Lamaze, Bradley, and home-birth approaches, which place more or less reliance on
      medical technology. Aristotle's analysis of three levels of human activity-
      digestion and reproduction, perception and locomotion, and abstract thinking--and
      Pellegrino and Thomasma's classification of the "living body," "lived body," and
      "lived self," provide a principled framework in which each of these childbirth
      practices can be considered natural.

PMID- 15259209
TI  - "What's my DNA worth, anyway?": a response to the commercialization of
      individuals' DNA information.
AB  - Extensive enthusiasm surrounds the potential for human DNA information to sustain
      and enhance the pharmaceutical industry's profitability. Nevertheless, persons
      whose health makes their DNA of commercial interest are routinely expected simply
      to give their DNA and the information in it to pharmaceutical or genomics
      companies or their academic intermediaries, voluntarily and without compensation.
      This state of affairs is increasingly recognized as paradoxical, but it is
      favored by conventional bioethical opinion. Given that most DNA information is
      now collected for commercial purposes and is worth considerably more than is
      generally imagined, bioethical objections to compensation of individuals for
      their DNA information are inappropriate. This paper suggests approaches by which
      individuals and representative governments and patient interest groups can
      negotiate compensation. Appreciable attitudinal change is required if those
      individuals personally involved are to be included fairly in the
      commercialization of human DNA information. Ultimately, however, such change is
      necessary if commercial genetic research is to respect human dignity and human
      rights.

PMID- 15259210
TI  - A traffic of dead bodies.

PMID- 15259211
TI  - ADSA Foundation Scholar Award: defining dairy flavors.
AB  - Production and consumption of dairy foods continue to increase annually. Further,
      new ingredient applications for dairy foods continue to expand. With continued
      production and consumption, there is also increased competition. Increased
      competition exists regionally, nationally, and globally. Processors as well as
      product developers must find ways to maximize existing markets and expand into
      new markets. A consistent high quality product is necessary to maintain
      competitiveness. Although microbial safety and stability are key ways to define
      quality, flavor is one method of defining quality that is often assumed or
      overlooked. The aggressive and competitive nature of today's market demands more
      precise and powerful tools for defining flavor and flavor quality. Traditional as
      well as more recent methods for evaluating dairy flavor are reviewed. The
      application of defining sensory flavors to fundamental research on flavor
      chemistry, product understanding, and effective marketing is addressed.

PMID- 15259212
TI  - Invited review: beta-lactoglobulin: binding properties, structure, and function.
AB  - beta-Lactoglobulin (beta-LG) is the major whey protein of ruminant species and is
      also present in the milks of many, but not all, other species. Its amino-acid
      sequence and 3-dimensional structure show that it is a lipocalin, a widely
      diverse family, most of which bind small hydrophobic ligands and thus may act as
      specific transporters, as does serum retinol binding protein. Bovine beta-LG
      binds a wide range of ligands, but this may not be the reason for its presence in
      milk. In reviewing the structure and physicochemical properties of the protein,
      we present the structures of the ligands cholesterol (at a resolution of 2.0A, R
      = 0.221; Rfree = 0.295) and vitamin D2 (at a resolution of 2.4A, R = 0.212; Rfree
      = 0.297) each bound to the central binding cavity of bovine beta-LG at pH 7.3.
      Neither ligand is fully visible in the electron density maps, and the less well
      ordered regions are the polar end groups at the mouth of the binding site. In a
      separate experiment, a mercury ion was bound to the free Cys121 (at a resolution
      of 2.2A, R = 0.218; Rfree = 0.288) in a way that transmitted a small structural
      change through Asp137 via Arg148 to the dimer interface. It is not clear if the
      known dissociation that arises from the reaction of beta-LG with HgCl2 results
      from this perturbation. In reviewing the structural studies that reveal the
      ligand binding sites for long-chain fatty acids, retinoids, and steroids, only
      the central location, common to all lipocalins so far examined, is occupied under
      the conditions used. We find that there is no crystallographic evidence of
      another ligand binding site in our crystals grown in approximately 1.3 M citrate,
      although low ionic strength studies in solution indicate the possible presence of
      at least one other low affinity site. The apparent ability of the binding site to
      accommodate a wide range of ligands may point to a possible physiological
      function. However, by considering the lipocalin family in general, and the
      species distribution of beta-LG in particular, some speculation as to the
      physiological function can be made. beta-Lactoglobulin has been reported as being
      implicated, inter alia, in hydrophobic ligand transport and uptake, enzyme
      regulation, and the neonatal acquisition of passive immunity. However, these
      functions do not appear to be consistent between species. Sequence comparisons
      among members of the lipocalin family reveal that glycodelin, found in the human
      endometrium during early pregnancy, is the most closely related to beta-LG.
      Although the function of glycodelin is also unknown, it appears to have effects
      on the immune system and/or to be involved in differentiation. It is proposed
      that beta-LG, over-expressed in the lactating mammary gland of many, but not all,
      species, is primarily an important source of amino acids for the offspring of
      those animals that produce it, but that this function arose by gene duplication
      from the physiologically essential glycodelin. The other functions that have been
      associated with beta-LG in the neonate are, therefore, fortuitous.

PMID- 15259213
TI  - Invited review: formation of keratins in the bovine claw: roles of hormones,
      minerals, and vitamins in functional claw integrity.
AB  - Keratins are the characteristic structural proteins of the highly cornified
      epidermis of the skin, feathers, and hoof. Keratin proteins provide the
      structural basis for the unique properties of the biomaterial horn and its
      protective function against a wide range of environmental factors. Hoof horn is
      produced through a complex process of differentiation (keratinization) of
      epidermal cells. Formation and biochemical binding of keratin proteins and
      synthesis and exocytosis of intercellular cementing substance (ICS) are the
      hallmarks of keratinization. It is finalized by the programmed death of the
      living epidermal cells, i.e., cornification, that turns the living epidermal
      cells into dead horn cells. The latter become connected by the intercellular
      cementing substance. The functional integrity of hoof horn essentially depends on
      a proper differentiation, i.e., keratinization of hoof epidermal cells.
      Keratinization of hoof epidermis is controlled and modulated by a variety of
      bioactive molecules and hormones. This process is dependent on an appropriate
      supply of nutrients, including vitamins, minerals, and trace elements. Regulation
      and control of differentiation and nutrient flow to the epidermal cells play a
      central role in determining the quality and, consequently, the functional
      integrity of hoof horn. Decreasing nutrient supply to keratinizing epidermal
      cells leads to horn production of inferior quality and increased susceptibility
      to chemical, physical, or microbial damage from the environment. A growing body
      of evidence suggests that hormones, vitamins, minerals, and trace elements play
      critical roles in the normal development of claw horn and correct keratin
      formation.

PMID- 15259214
TI  - Short communication: impact of formulation on ice cream microstructures: an
      oscillation thermo-rheometry study.
AB  - Oscillation thermo-rheometry was used to underline the existence of the different
      microstructures in ice cream. Varying ice cream formulations illustrated the
      impact of each ingredient, i.e., fat, proteins, and lipid emulsifiers, and their
      interactions on the establishment of different networks.

PMID- 15259215
TI  - Short communication: growth characteristics of Streptococcus uberis in UHT
      treated milk.
AB  - Streptococcus uberis is an important environmental pathogen associated with
      bovine mastitis as well as with high total bacterial numbers in bulk tank milk.
      This study was conducted to determine whether S. uberis reproduction is likely to
      contribute to high bacterial numbers in bulk tank milk. Four S. uberis raw milk
      isolates were individually inoculated into UHT-treated milk and incubated at 4.4
      or 7 degrees C for up to 5 d to simulate appropriate cooling; at 10 degrees C for
      5 d to simulate marginally inadequate cooling; at 21 or 25 degrees C for 7 h to
      simulate ambient temperatures; or at 32 degrees C for 7 h to simulate elevated
      temperature conditions. None of the S. uberis isolates grew at either 4.4 or 7
      degrees C. Streptococcus uberis growth at 10 degrees C appeared to be ribotype
      specific. Although ribotype 116-520-S-1 isolates did not grow at 10 degrees C,
      ribotype 116-520-S-2 isolate numbers increased up to 3.5 log10 cfu/mL within 5 d.
      Generation times were calculated as 2.7 +/- 0.1 h, 2.1 +/- 0.1 h, and 1.0 +/- 0.1
      h for 116-520-S-1 isolates and 1.8 +/- 0.4 h, 1.3 +/- 0.3 h, and 0.8 +/- 0.1 h
      for 116-520-S-2 isolates at 21, 25, and 32 degrees C, respectively. Our results
      suggest that high numbers of S. uberis in bulk tank milk are more likely to
      reflect high numbers of S. uberis shed by mastitic cows, rather than
      multiplication of these organisms under cooling conditions required for
      production of Grade A milk.

PMID- 15259216
TI  - Composition and aroma compounds of Ragusano cheese: native pasture and total
      mixed rations.
AB  - Raw milk from 13 cows fed TMR supplemented with native pasture and from 13 cows
      fed only TMR on one farm was collected separately 4 times with an interval of 15
      d between collections. Two blocks (14 kg each) of cheese were made from each
      milk. The objective was to determine the influence of consumption of native
      plants in Sicilian pastures on the aroma compounds present in Ragusano cheese.
      Milk from cows that consumed native pasture plants produced cheeses with more
      odor-active compounds. In 4-mo-old cheese made from milk of pasture-fed cows, 27
      odor-active compounds were identified, whereas only 13 were detected in cheese
      made from milk of total mixed ration-fed cows. The pasture cheeses were much more
      rich in odor-active aldehyde, ester, and terpenoid compounds than cheeses from
      cows fed only total mixed ration. A total of 8 unique aroma-active compounds
      (i.e., not reported in other cheeses evaluated by gas chromatography olfactory)
      were detected in Ragusano cheese made from milk from cows consuming native
      Sicilian pasture plants. These compounds were 2 aldehydes ([E,E]-2,4-octadienal
      and dodecanal), 2 esters (geranyl acetate and [E]-methyl jasmonate), 1 sulfur
      compound (methionol), and 3 terpenoid compounds (1-carvone, L(-) carvone, and
      citronellol). Geranyl acetate and (E)-methyl jasmonate were particularly
      interesting because these compounds are released from fresh plants as they are
      being damaged and are part of a possible plant defense mechanism against damage
      from insects. Most of the odor-active compounds that were unique in Ragusano
      cheese from pasture-fed cows appeared to be compounds created by oxidation
      processes in the plants that may have occurred during foraging and ingestion by
      the cow. Some odor-active compounds were consistently present in pasture cheeses
      that were not detected in the total mixed ration cheeses or in the 14 species of
      pasture plants analyzed. Either these compounds were present in other plants not
      analyzed, created in the rumen or in cheese after the pasture-plant material had
      been consumed, or the compounds were lost in the method of sample extraction used
      for the plant analysis (i.e., steam distillation) versus the solid-phase
      microextraction method used for the cheeses. This research has demonstrated
      clearly that some unique odor-active compounds found in pasture plants can be
      transferred to the cheese.

PMID- 15259217
TI  - Production of a high gel strength whey protein concentrate from cheese whey.
AB  - In order to develop a process for the production of a whey protein concentrate
      (WPC) with high gel strength and water-holding capacity from cheese whey, we
      analyzed 10 commercially available WPC with different functional properties.
      Protein composition and modification were analyzed using electrophoresis, HPLC,
      and mass spectrometry. The analyses of the WPC revealed that the factors closely
      associated with gel strength and water-holding capacity were solubility and
      composition of the protein and the ionic environment. To maintain whey protein
      solubility, it is necessary to minimize heat exposure of the whey during
      pretreatment and processing. The presence of the caseinomacropeptide (CMP) in the
      WPC was found to be detrimental to gel strength and water-holding capacity. All
      of the commercial WPC that produced high-strength gels exhibited ionic
      compositions that were consistent with acidic processing to remove divalent
      cations with subsequent neutralization with sodium hydroxide. We have shown that
      ultrafiltration/diafiltration of cheese whey, adjusted to pH 2.5, through a
      membrane with a nominal molecular weight cut-off of 30,000 at 15 degrees C
      substantially reduced the level of CMP, lactose, and minerals in the whey with
      retention of the whey proteins. The resulting WPC formed from this process was
      suitable for the inclusion of sodium polyphosphate to produce superior functional
      properties in terms of gelation and water-holding capacity.

PMID- 15259218
TI  - Reduced-fat cheddar cheese manufactured using a novel fat removal process.
AB  - Normally, reduced-fat Cheddar cheese is made by removal of fat from milk prior to
      cheese making. Typical aged flavor may not develop when 50% reduced-fat Cheddar
      cheese is produced by this approach. Moreover, the texture of the reduced-fat
      cheeses produced by the current method may often be hard and rubbery. Previous
      researchers have demonstrated that aged Cheddar cheese flavor intensity resides
      in the water-soluble fraction. Therefore, we investigated the feasibility of fat
      removal after the aging of Cheddar cheese. We hypothesized the typical aged
      cheese flavor would remain with the cheese following fat removal. A physical
      process for the removal of fat from full-fat aged Cheddar cheese was developed.
      The efficiency of fat removal at various temperatures, gravitational forces, and
      for various durations of applied forces was determined. Temperature had the
      greatest effect on the removal of fat. Gravitational force and the duration of
      applied force were less important at higher temperatures. A positive linear
      relationship between temperature and fat removal was observed from 20 to 33
      degrees C. Conditions of 30 degrees C and 23,500 x g for 5 min removed 50% of the
      fat. The removed fat had some aroma but little or no taste. The fatty acid
      composition, triglyceride molecular weight distribution, and melting profile of
      the fat retained in the reduced-fat cheeses were all consistent with a slight
      increase in the proportion of saturated fat relative to the full-fat cheeses. The
      process of fat removal decreased the grams of saturated fat per serving of cheese
      from 6.30 to 3.11 g. The flavor intensity of the reduced-fat cheeses were at
      least as intense as the full-fat cheeses.

PMID- 15259219
TI  - Changes in the proportions of soluble and insoluble calcium during the ripening
      of cheddar cheese.
AB  - In cheese, the concentration and form of residual Ca greatly influences texture.
      Two methods were used to determine the proportions of soluble (SOL) and insoluble
      (INSOL) Ca in Cheddar cheese during 4 mo of ripening. The first method was based
      on the acid-base buffering curves of cheese and the second was based on the
      extraction of the aqueous phase ("juice") of cheese under high pressure and
      determining the concentration of SOL Ca in the juice using atomic absorption
      spectroscopy. When cheese was acidified there was a strong buffering peak at pH
      approximately 4.8, which was due to the solubilization of residual colloidal
      calcium phosphate (CCP) of milk that remained in cheese as INSOL Ca phosphate.
      The area of this buffering peak in cheese was expressed as a percentage of the
      original area of this peak in milk and was used to estimate the concentration of
      residual INSOL Ca phosphate in cheese. There were no significant differences
      between the 2 methods. The proportions of INSOL Ca in cheese decreased from
      approximately 73 to approximately 58% between d 1 and 4 mo. These methods will be
      useful techniques to study the role of Ca in cheese texture and functionality.

PMID- 15259220
TI  - Factors affecting solubility of calcium lactate in aqueous solutions.
AB  - Calcium lactate (CaL2) crystal formation on the surface of cheese continues to be
      a widespread problem for the cheese industry despite decades of research. To
      prevent those crystals from forming, it is necessary to keep the concentration of
      CaL2 below saturation level. The limited data available on the solubility of CaL2
      at conditions appropriate for the storage of cheese are often conflicting. In
      this work, the solubility of L(+)-CaL2 in water was evaluated at 4, 10, and 24
      degrees C, and the effects of salt and pH at those temperatures were
      investigated. The effects of additional calcium and lactate ions on solubility
      also were studied. The results suggested that temperature and the concentration
      of lactate ions are the main factors influencing the solubility of CaL2, with the
      other parameters having limited effect.

PMID- 15259221
TI  - Effect of bST and reproductive management on reproductive performance of Holstein
      dairy cows.
AB  - The objective was to determine the effects of bovine somatotropin (bST) and two
      artificial insemination (AI) protocols on reproductive performance of Holstein
      cows. Lactating cows (n = 840) were assigned at 37 d in milk (DIM) to one of four
      treatments in a 2 x 2 factorial arrangement. Treatments consisted of either bST
      (500 mg/14 d) starting at 63 +/- 3 DIM or no bST (control), with cows either
      submitted for timed AI following a synchronized ovulation (Ovsynch) protocol or
      assigned to receive AI based on estrus detection (ED). Two injections of PGF2, at
      37 +/- 3 and 51 +/- 3 DIM were used to presynchronize estrous cycles. Cows then
      received an injection of GnRH at 63 +/- 3 DIM, followed 7.5 d later by PGF2. Cows
      assigned to ED treatments were inseminated after observed estrus during a 7-d
      period. Cows in Ovsynch treatments received a second GnRH injection 48 h after
      the last PGF2alpha and received timed AI 16 to 18 h later. Pregnancy was
      diagnosed by ultrasound at 31 d after AI and confirmed 14 d later. Frequency of
      anovulation (18.5%) at 63 DIM was similar across treatments, but proportions of
      anovulatory cows decreased quadratically as body condition at 70 DIM increased
      from 2.25 to 3.75. Estrus detection rate after PGF2alpha tended to be lower in
      multiparous cows receiving bST, and bST reduced returns to estrus in nonpregnant
      cows. Conception rates were higher in cows receiving AI after ED and bST improved
      conception rates to first AI in cyclic cows by reducing embryonic mortality.
      Pregnancy loss was similar for cows inseminated following ED or the Ovsynch
      protocol. There was a positive impact of bST on fertility of cyclic cows
      inseminated at fixed time or at detected estrus, but effective resynchronization
      protocols are needed to optimize reinsemination of non-pregnant bST-treated cows.

PMID- 15259222
TI  - Hot topic: effects of frequent milking in early lactation on milk yield and udder
      health.
AB  - A field study was conducted to evaluate the influence of milking frequency (3 or
      6 times/d [3x or 6x, respectively]) during the initial 21 d of lactation on milk
      and milk component yield and mammary gland health as indicated by somatic cell
      count. During 2 seasons, spring and fall, multiparous cows were milked 6 times/d
      until d 21 of lactation and then returned to the 3 times/d frequency for the
      remainder of lactation (6x; n = 9). Multiparous cows milked 3 times/d from the
      beginning of lactation served as a control group (3x; n = 17). With the exception
      of milking frequency, all other aspects of management, including housing, milk
      harvesting, and feeding, were identical between the groups and were consistent
      with industry norms. Retrospective analysis of Dairy Herd Improvement Association
      records was used to evaluate milk yield, milk component yield, and somatic cell
      scores. As expected, 6x cows produced more milk on the first test day than 3x
      cows. Compared with 3x cows, higher milk yields persisted for 6x cows from test
      day 2 through 6, indicating a persistent effect of early lactation milking
      frequency on milk yield potential for that lactation. Milk component yield
      followed a similar pattern: 6x cows produced significantly more protein, fat, and
      total solids than did control cows throughout the study. With regard to udder
      health, 6x cows had lower somatic cell counts at the first test day relative to
      3x cows and had reduced somatic cell scores for the first 3 mo of lactation,
      which suggests that early lactation milking frequency influences the mammary
      gland capacity to resist infection in addition to improving milk production
      efficiency.

PMID- 15259223
TI  - Moderate inflammatory reaction during experimental Escherichia coli mastitis in
      primiparous cows.
AB  - Nineteen primiparous cows were experimentally infected in 2 quarters with 1 x
      10(4) (group A) or 1 x 10(6) (group B) cfu of Escherichia coli P4:O32 per quarter
      within 2 to 4 wk after parturition. Blood and milk samples were collected from
      all primiparous cows at regular time intervals from d -4 to d +3 relative to
      inoculation. Milk production rapidly decreased in both groups during E. coli
      mastitis, but recovery appeared to be faster in group B at d + 1 postinfusion
      (p.i.). The milk production losses in the noninfected quarters were substantial
      on the day of inoculation, which is probably due to pronounced systemic effects.
      However, on d + 2 p.i. milk production in the noninfected quarters nearly reached
      preinfection levels, indicating a moderate clinical severity following
      intramammary inoculation. None of the other severity criteria evolved towards a
      severe response pattern. Reticulorumen motility was inhibited in both groups
      during E. coli mastitis. The clinical episode was short lasting in both groups.
      Rectal temperature, heart rate, blood leukocyte count, number of colony-forming
      units, milk somatic cell count and several indicators for the disintegration of
      the blood-milk barrier returned to normal values within 24 to 72 h p.i.
      Primiparous cows reacted with a moderate inflammatory response following
      intramammary infusion with a relatively high dose of E. coli. Despite the use of
      a high inoculum dose, primiparous cows in both groups showed pronounced
      resistance against severe intramammary E. coli infection. A possible effect of
      the inoculum dose could be present, however, further research into the effect of
      the inoculum dose on the inflammatory response should be performed.

PMID- 15259224
TI  - Exogenous TGF-beta1 promotes stromal development in the heifer mammary gland.
AB  - The objectives of this study were to determine the local effects of transforming
      growth factor-beta1 (TGF-beta1) on mammary epithelial and stromal cell
      proliferation and expression of the TGF-beta1 responsive genes c-myc and
      fibronectin. A single slow-release plastic pellet containing 5 microg of TGF
      beta1 and 20 mg of BSA was implanted in the parenchyma of the right rear quarter
      of the mammary gland of 9-mo-old prepubertal heifers. A control pellet containing
      20 mg of BSA was implanted in the left rear quarter of each heifer. All heifers
      were treated with bromodeoxyuridine (BrdU) at 4, 12.5, and 22 h after the pellets
      were implanted to label proliferating cells. Two hours after the last BrdU
      injection, the animals were euthanatized, and their mammary glands were
      recovered. Proliferation of mammary stromal cells was significantly higher in TGF
      beta1-treated quarters than in BSA-treated, control quarters (3.5 vs. 1.8% BrdU
      positive cells). This result coincided with a lack of significant effect of TGF
      beta1 on proliferation of mammary epithelial cells and apoptosis. By quantitative
      reverse transcriptase-polymerase chain reaction, we found that c-myc gene
      expression was unchanged after TGF-beta1 treatment, but fibronectin gene
      expression was increased 3-fold in TGF-beta1-treated quarters compared with BSA
      treated, control quarters. Thus, we concluded that TGF-beta1 selectively acts on
      the stromal compartment of the bovine mammary gland by increasing cell
      proliferation and gene expression of the extracellular matrix protein
      fibronectin.

PMID- 15259225
TI  - Comparison of ovarian function and circulating steroids in estrous cycles of
      Holstein heifers and lactating cows.
AB  - Ovarian function was compared between nulliparous heifers (n = 29; 10 to 16 mo
      old) and lactating Holstein cows (n = 31; 55.9 +/- 3.5 d postpartum). Follicular
      dynamics, corpus luteum growth, and regression, and serum steroid concentrations
      were evaluated through ultrasonography and daily blood sampling. Most heifers (27
      of 29) but only 14 of 31 cows had typical spontaneous estrous cycles after cycles
      were initiated. Twelve cows had atypical cycles, and 5 became anovulatory during
      the study. The 12 cows with atypical estrous cycles had low serum estradiol after
      luteolysis and failed to ovulate the dominant follicle present at luteolysis.
      Heifers and cows with typical cycles were compared directly. Interovulatory
      intervals were similar between heifers (22.0 +/- 0.4 d) and cows (22.9 +/- 0.7
      d). Those animals had estrous cycles with either 2 (15 heifers; 11 cows), 3 (9
      heifers; 2 cows), or 4 follicular waves (3 heifers; 1 cow). Cows ovulated later
      after luteolysis than heifers (5.2 +/- 0.2 vs. 4.6 +/- 0.1 d, respectively), and
      had more multiple ovulations (17.9 vs. 1.9%). Maximal serum estradiol
      concentration preceding ovulation was lower in cows than in heifers (7.9 +/- 0.8
      vs. 11.3 +/- 0.6 pg/mL) even though ovulatory follicles were larger in cows (16.8
      +/- 0.5 vs. 14.9 +/- 0.2 mm). Similarly, maximal serum progesterone concentration
      was lower for cows (5.6 +/- 0.5 vs. 7.3 +/- 0.4 ng/mL), whereas maximal volume of
      luteal tissue was larger for cows than heifers (11,120 +/- 678 vs. 7303 +/- 308
      mm3). Thus, higher incidence of reproductive anomalies in lactating cows, such as
      low conception rate, ovulation failure, delayed ovulation, and multiple
      ovulations, may be due to lower circulating steroid concentrations in spite of
      larger ovulatory follicles and luteal structures.

PMID- 15259226
TI  - The effects of feeding fish oil on uterine secretion of PGF2alpha, milk
      composition, and metabolic status of periparturient Holstein cows.
AB  - The objectives were to determine the effect of dietary fish oil (FO) on uterine
      secretion of PGF2alpha, milk production, milk composition, and metabolic status
      during the periparturient period. Holstein cows were assigned randomly to diets
      containing FO (n = 13) or olive oil (OO, n = 13). Cows were fed prepartum and
      postpartum diets that provided approximately 200 g/d from 21 d before the
      expected parturition until 21 d after parturition. The FO used contained 36%
      eicosapentaenoic acid (EPA, C20:5, n-3) and 28% docosahexaenoic acid (DHA, C22:6,
      n-3). Blood samples were obtained from 14 d before the due date until d 21
      postpartum. A total of 6 FO and 8 OO cows without periparturient disorders were
      used in the statistical analyses of PGF2alpha-metabolite (PGFM) and metabolite
      concentrations. Length of prepartum feeding with OO or FO did not differ.
      Proportions of individual and total n-3 fatty acids were increased in caruncular
      tissue and milk of cows fed FO. The combined concentrations of EPA and DHA in
      caruncular tissue were correlated positively with the number of days supplemented
      with FO. Cows fed FO had reduced concentrations of plasma PGFM during the 60 h
      immediately after parturition compared with cows fed OO. Concentrations of
      prostaglandin H synthase-2 mRNA and protein in caruncular tissue were unaffected
      by diet. Production of milk and FCM were similar between cows fed the two oil
      diets. However, cows fed FO produced less milk fat. Feeding FO reduced plasma
      concentrations of glucose. Dietary fatty acids given during the periparturient
      period can reduce the uterine secretion of PGF2alpha in lactating dairy cows and
      alter the fatty acid profile of milk fat.

PMID- 15259227
TI  - Effects of storage time and thawing methods on the recovery of Mycoplasma species
      in milk samples from cows with intramammary infections.
AB  - This study was executed to determine the effects of storage and thawing on the
      viability of Mycoplasma spp. in milk from cows with intramammary infections. The
      trial was designed using a control sample and seven handling regimens subjected
      to two methods of thawing. There was a significant treatment effect on the
      recovery of colony-forming units in milk samples when comparing the control
      sample with handling regimens 1 through 7. There was a continuous decline in log
      (10) mean number of cfu/mL recovered. Mean concentrations were 6.29, 4.64, 3.69,
      3.01, 1.86, 4.41, 4.13, and 3.18 for control and handling regimens 1 to 7,
      respectively. To determine the best thawing method, handling regimen 1 through 7
      samples were thawed using two methods. On average, more mycoplasma were recovered
      from milk samples thawed at ambient temperature (4.04 cfu/mL) than milk samples
      thawed in a 37 degrees C water bath (3.76 cfu/mL). A final comparison was made
      between individual treatments. With the exception of the handling regimen 5 to 6
      pair-wise comparison, all pair-wise comparisons between handling regimens were
      significantly different. The results of this study indicate that storage and
      thawing of milk samples is harmful to mycoplasma organisms. Fresh samples should
      be used to improve detection of Mycoplasma spp. from milk of infected cattle. If
      frozen samples are used, then length of storage time should be minimized, and
      thawing milk at ambient temperature will improve recovery of mycoplasma as
      opposed to thawing in a 37 degrees C water bath.

PMID- 15259228
TI  - Management practices and heifer characteristics associated with early lactation
      somatic cell count of Belgian dairy heifers.
AB  - Associations between somatic cell counts (SCC) from heifers between 5 and 14 d in
      milk (DIM) and both herd-management practices and heifer characteristics were
      studied for 1912 heifers in 159 dairy herds in Flanders (Belgium). In higher
      producing herds and in herds with an average calving age of heifers > 27 mo, SCC
      of heifers was lower than in less-producing herds or in herds with an average
      calving age < or = 27 mo. Heifers raised in herds with a higher bulk-milk somatic
      cell count had higher SCC. In herds in which heifers calved on slatted floors,
      heifers had lower SCC compared with herds in which heifers calved on nonslatted
      floors. A significant difference in SCC was observed between provinces. At the
      heifer level, SCC decreased with increasing DIM. On average, heifers calving in
      April to June had higher SCC, compared with those calving in the other months of
      the year. In the multilevel regression models, nearly all the variations of SCC
      resided at the heifer level, indicating that preventive measures against udder
      health problems in freshening dairy heifers should, in the short term, focus more
      on factors that vary between heifers than on factors that vary between herds.
      However, for the long term, the need to identify new, and to implement known,
      herd-level strategies is important.

PMID- 15259229
TI  - Low doses of bovine somatotropin during the transition period and early lactation
      improves milk yield, efficiency of production, and other physiological responses
      of Holstein cows.
AB  - The objectives of this experiment were to determine whether low doses of bovine
      somatotropin (bST) during the transition period and early lactation period
      improved dry matter intake (DMI), body weight (BW), or body condition score
      (BCS); provoked positive changes in concentrations of somatotropin, insulin,
      insulin-like growth factor-I (IGF-I), glucose, nonesterified fatty acids, and Ca;
      or improved milk yield (MY) response without obvious adverse effects on health
      status. Eighty-four multiparous Holstein cows completed treatments arranged in a
      2 x 3 x 2 factorial design that included prepartum and postpartum bST, dry period
      (30 d dry, 30 d dry + estradiol cypionate, and 60 d dry), and prepartum anionic
      or cationic diets. Biweekly injections of bST began at 21 +/- 3 d before expected
      calving date through 42 +/- 2 d postpartum (control = 0 vs. bST = 10.2 mg of
      bST/d; POSILAC). At 56 +/- 2 d in milk, all cows were injected with a full dose
      of bST (500 mg of bST/14 d; POSILAC). During the prepartum period and during the
      first 28 d postpartum, no differences in mean BW, BCS, or DMI were detected
      between the bST treatment group and the control group. During the first 10 wk of
      lactation, cows in the bST treatment group had greater mean MY and 3.5% fat
      corrected milk yield and lower SCC than did cows in the control group. When cows
      received a full dose of bST, an increase in milk production through wk 21 was
      maintained better by cows in the bST group. Mean concentrations of somatotropin,
      IGF-I, and insulin differed during the overall prepartum period (d -21 to -1).
      During the postpartum period (d 1 to 28), cows in the bST group had greater mean
      concentrations of somatotropin and IGF-I in plasma. Concentrations of Ca around
      calving did not differ because of bST treatment. Results suggest that changes in
      concentrations of blood measures provoked by injections of bST during the
      transition period and early lactation period resulted in improved metabolic
      status and production of the cows without apparent positive or negative effects
      on calving or health.

PMID- 15259230
TI  - Visceral tissue mass and rumen volume in dairy cows during the transition from
      late gestation to early lactation.
AB  - The objectives were to measure the effects of transition and supplemental barley
      or rumen-protected protein on visceral tissue mass in dairy cows and the effects
      of transition and barley on rumen volume and liquid turnover. Cows were
      individually fed a grass silage-based gestation ration to meet energy and protein
      requirements for body weight stasis beginning 6 wk before expected calving. A
      corn silage-based lactation ration was individually fed ad libitum after calving.
      In the visceral mass study, 36 cows were randomly assigned to one of 3 dietary
      treatments: basal ration or basal ration plus either 800 g dry matter (DM) of
      barley meal per day or 750 g DM of rumen-protected soybean protein per day. Cows
      were slaughtered at 21 and 7 d before expected calving date or at 10 and 22 d
      postpartum. Visceral mass and rumen papillae characteristics were measured. Diets
      had little effect on visceral mass. The mass of the reticulo-rumen, small
      intestine, large intestine, and liver was, or tended to be, greater at 22 d
      postpartum but not at 10 d postpartum before DM intake had increased. Rumen
      papillae mass increased at 10 d postpartum, perhaps in response to increased
      concentrates. Mesenteric fat decreased after calving, reflecting body fat
      mobilization. Ten rumen-cannulated cows were fed the basal gestation ration alone
      or supplemented with 880 g of barley meal DM. Rumen volumes and liquid dilution
      rates were measured at 17 and 8 d before calving and at 10, 20, and 31 d
      postpartum. Feeding barley had no effects. After calving, rumen DM volume and
      liquid dilution rate increased, but liquid volume did not increase. Changes in
      gastrointestinal and liver mass during transition were apparently a consequence
      of changes in DM intake and nutrient supply and not initiation of lactation per
      se.

PMID- 15259231
TI  - Effect of simultaneous thawing of multiple 0.5-mL straws of semen and sequence of
      insemination on conception rate in dairy cattle.
AB  - The objectives of this study were to determine 1) the effect of simultaneous
      thawing of multiple 0.5-mL straws of semen and sequence of insemination (first,
      second, third, or fourth) on conception rates in dairy cattle, 2) whether the
      conception rates achieved following AI by professional AI (PAI) technicians and
      herdsman-inseminators (HI) differed, and 3) the effect of elapsed time from
      initiation of thawing straws of semen to seminal deposition on conception rates
      in dairy cattle. Four dairies with PAI and four with HI participated in the
      study. Initial data recorded included beginning thaw time, cow identification
      number, and time of seminal deposition. Herd records were retrieved following
      pregnancy diagnosis. Conception rates of dairy cows (n = 1025) were not affected
      by sequence of insemination (first, second, third, or fourth). Conception rates
      for herds using PAI were 40, 47, 41, and 50%. Conception rates for herds using HI
      were 24, 20, 33, and 30%. Average conception rates of dairy cows differed between
      PAI and HI (45 vs. 27%, respectively). The difference in mean conception rate
      achieved by PAI and HI was not attributable to milk production, parity, service
      number or stage of lactation. The elapsed time from initial thaw to completion of
      fourth AI was shorter for PAI than for HI, 7.6 vs. 10.9 min, respectively.
      Although the average conception rate differed between PAI and HI, elapsed time
      from initial thaw to completion of fourth AI and sequence of insemination (first,
      second, third, or fourth) had no effect on conception rate within inseminator
      group.

PMID- 15259232
TI  - Short communication: influence of Staphylococcus aureus intramammary infection on
      serum copper, zinc, and iron concentrations.
AB  - The goal of the present study was to characterize changes in serum trace mineral
      concentrations in cattle with experimentally induced Staphylococcus aureus
      mastitis. Nine primiparous Holstein-Friesian cattle were challenged with
      approximately 150 cfu of Staph. aureus ATCC29740 by intramammary infusion on d 6,
      7, and 8 of lactation. Serum Cu, Zn, and Fe concentrations were determined
      immediately before and at 24, 48, and 72 h after the final intramammary infusion
      of Staph. aureus. Infection status (cfu/mL of Staph. aureus), milk somatic cell
      count, and mastitis score were also determined at these times. Infection resulted
      in a decrease in mean serum Cu, Zn, and Fe concentrations to 89, 83, and 81% of
      preinfection concentrations at 24 h postchallenge. One-way analysis of variance
      for repeated measures demonstrated a significant change in serum zinc
      concentration. The reductions in trace mineral concentrations were of less
      magnitude than observed following experimental E. coli mastitis.

PMID- 15259233
TI  - All-trans retinoic acid is increased in the acute phase-related hyporetinemia
      during Escherichia coli mastitis.
AB  - Blood vitamin A profiles, including concentrations of retinol and its active
      metabolite retinoic acid, were assessed during the peripartum period and during
      experimentally induced Escherichia coli mastitis in heifers. Serum retinol
      decreased in all animals in the immediate postpartum period and normalized within
      1 wk after parturition. No significant changes were detectable in the
      concentrations of retinoic acid isomers during puerperium. Following intramammary
      E. coli infusion, all cows showed moderate symptoms of systemic disease besides
      the local signs of inflammation. The presence of a systemic acute-phase reaction
      was documented by fever, increase in serum amyloid A, and decrease in serum
      albumin. Retinol concentration in serum also decreased spectacularly during
      coliform mastitis, and the decline was clearly related to the timing of the acute
      phase response. Moreover, a significant increase of all-trans retinoic acid,
      mirrored by a lowering of 13-cis retinoic acid, was detected during the same time
      period. The 9-cis isomer of retinoic acid was present in all samples, but it
      remained below the quantification limit. Results confirmed the decrease in serum
      retinol during the peripartum period of dairy cows. Furthermore, the study
      established that profound changes in vitamin A metabolism occur during the acute
      phase reaction of coliform mastitis in heifers. The bovine infection model
      reproduced the acute phase-related hyporetinemia, as previously observed in
      humans and rats. In addition, all-trans retinoic acid was found to be the most
      abundant circulating acid isomer during mastitis, providing an indication for a
      possible key role of all-trans retinoic acid in the modulation of the immune
      response.

PMID- 15259234
TI  - Prediction of body lipid change in pregnancy and lactation.
AB  - A simple method to predict the genetically driven pattern of body lipid change
      through pregnancy and lactation in dairy cattle is proposed. The rationale and
      evidence for genetically driven body lipid change have their basis in
      evolutionary considerations and in the homeorhetic changes in lipid metabolism
      through the reproductive cycle. The inputs required to predict body lipid change
      are body lipid mass at calving (kg) and the date of conception (days in milk).
      Body lipid mass can be derived from body condition score and live weight. A key
      assumption is that there is a linear rate of change of the rate of body lipid
      change (dL/dt) between calving and a genetically determined time in lactation
      (T') at which a particular level of body lipid (L') is sought. A second
      assumption is that there is a linear rate of change of the rate of body lipid
      change (dL/dt) between T' and the next calving. The resulting model was evaluated
      using 2 sets of data. The first was from Holstein cows with 3 different levels of
      body fatness at calving. The second was from Jersey cows in first, second, and
      third parity. The model was found to reproduce the observed patterns of change in
      body lipid reserves through lactation in both data sets. The average error of
      prediction was low, less than the variation normally associated with the
      recording of condition score, and was similar for the 2 data sets. When the model
      was applied using the initially suggested parameter values derived from the
      literature the average error of prediction was 0.185 units of condition score (+/
      0.086 SD). After minor adjustments to the parameter values, the average error of
      prediction was 0.118 units of condition score (+/- 0.070 SD). The assumptions on
      which the model is based were sufficient to predict the changes in body lipid of
      both Holstein and Jersey cows under different nutritional conditions and
      parities. Thus, the model presented here shows that it is possible to predict
      genetically driven curves of body lipid change through lactation in a simple way
      that requires few parameters and inputs that can be derived in practice. It is
      expected that prediction of the cow's energy requirements can be substantially
      improved, particularly in early lactation, by incorporating a genetically driven
      body energy mobilization.

PMID- 15259235
TI  - Relationships between milk urea and production, nutrition, and fertility traits
      in Israeli dairy herds.
AB  - The objectives of this study were to identify and evaluate production and
      environmental factors that influence milk urea (MU) in Israeli dairy herds, to
      analyze the relationships between MU concentration and nutritional variables, and
      to examine a possible association between MU and pregnancy rate (PR). Production
      and environmental data were obtained from the Israeli Dairy Herd Improvement
      (DHI) Center (n = 1,279,600). Programmed total mixed rations (feeds and
      quantities) on milk-test day were collected from 42 dairy herds. Data on 36,073
      cows that were inseminated close to milk-test day and pregnancy diagnosis results
      were obtained from the DHI data bank. Highly significant positive relationships
      were found between MU concentration and milk yield and fat percentage;
      relationships between MU and milk total protein percentage and somatic cell count
      were negative. Milk urea levels were higher during the summer months and were
      higher for adult cows. These levels increased as lactation progressed. Milk urea
      was positively associated with dietary levels of crude protein, ruminal
      digestible protein, and neutral detergent fiber contents; it was negatively
      associated with ration energy and nonstructural carbohydrate contents.
      Significant influences of specific feeds on MU were detected. A significant
      negative association was found between MU level and PR. Least squares means for
      PR for cows in the lowest and highest MU quartiles were 38.4 and 36.1%,
      respectively. Increasing levels of MU were negatively related to reproductive
      performance of dairy cows, but the risk of nonpregnancy caused by high levels of
      MU was lower than reported in previous studies.

PMID- 15259236
TI  - Short communication: effects of nonesterified fatty acids on lymphocyte function
      in dairy heifers.
AB  - This in vitro study was performed to assess the effects of various concentrations
      of nonesterified fatty acids (NEFA) on lymphocyte function of heifers. Nine
      Holstein heifers were studied. Peripheral blood mononuclear cells were incubated
      with various concentrations of NEFA (0, 0.0625, 0.125, 0.25, 0.5, 1, and 2
      mmol/L). The mixture of NEFA was represented by C16:0 (30%), C16:1 (5%), C18:0
      (15%), C18:1 (45%), and C18:2 (5%). The DNA synthesis was diminished at
      concentrations of NEFA of 2, 1, and 0.5 mmol/L. The IgM secretion was inhibited
      at concentrations of NEFA of 2, 1, 0.5, and 0.25 mmol/L. Secretion of IFN-gamma
      was depressed at concentrations of NEFA of 2, 1, 0.5, 0.25, and 0.125 mmol/L.
      Increases of plasma NEFA might contribute to explain the higher incidence of
      infections observed in cows suffering from energy deficit.

PMID- 15259237
TI  - The effect of housing and methionine intake on hoof horn hemorrhages in
      primiparous lactating Holstein cows.
AB  - This study investigated the effects of housing and nutrition on the development
      of hoof horn disease (as identified by the appearance of hoof horn hemorrhages)
      in primiparous lactating Holstein cows. The first objective was to investigate
      whether replacing butyl rubber mats in cubicles (free stalls) with thicker
      mattresses filled with chopped rubber would significantly reduce hoof horn
      hemorrhages, and if this reduction would so affect the level of hoof horn
      hemorrhages as to make it similar to that observed in primiparous cows in straw
      yards. The second objective was to investigate the effect of methionine
      supplementation for the first 13 wk of lactation on the development of such
      hemorrhages. This study confirmed that both sole and white line hemorrhages
      increase during early lactation in housed cows, although the pattern of
      development of white line hemorrhages is not identical to that of sole
      hemorrhages. Housing primiparous cows in straw yards after calving significantly
      reduced the development of hoof horn hemorrhages, but replacing cubicle mats with
      thicker mattresses had no significant effect. Providing 115% of calculated
      methionine requirements had no significant impact on the development of hoof horn
      hemorrhages.

PMID- 15259238
TI  - Pregnancy in dairy cows after synchronized ovulation regimens with or without
      presynchronization and progesterone.
AB  - Two experiments examined pregnancy after synchronized ovulation (Ovsynch) with or
      without progesterone (P4) administered via controlled internal drug release
      (CIDR) intravaginal inserts. In experiment 1, 262 lactating cows in one herd were
      in 3 treatments: Ovsynch (n = 91), Ovsynch + CIDR (n = 91), and control (n = 80).
      The Ovsynch protocol included injections of GnRH 7 d before and 48 h after an
      injection of PGF20. Timed artificial insemination (TAI; 57 to 77 d postpartum)
      was 16 to 20 h after the second GnRH injection. Cows in the Ovsynch + CIDR group
      also received a CIDR (1.9 g of P4) insert for 7 d starting at first GnRH
      injection. Control cows received A-I when estrus was detected using an electronic
      estrus detection system. Based on serum P4, 44.1% of cows were cyclic before
      Ovsynch. Pregnancy rates at 29 d (59.3 vs. 36.3%) and 57 d (45.1 vs. 19.8%) after
      TAI and embryo survival (75.9 vs. 54.5%) from 29 to 57 d were greater for Ovsynch
      + CIDR than for Ovsynch alone. In experiment 2, 630 cows in 2 herds received TAI
      at 59 to 79 d postpartum after 6 treatments. Estrous cycles were either
      presynchronized (2 injections of PGF2alpha 14 d apart; n = 318) or not
      presynchronized (n = 312). Within those groups, Ovsynch was initiated 12 d after
      second presynchronization PGF2alpha, and used alone (n = 318) or with CIDR
      inserts for 7 d (1.38 g of P4/insert, n = 124 or 1.9 g of P4/insert, n = 188).
      Before Ovsynch, 80% of cows were cyclic. Presynchronization increased pregnancy
      (46.8 vs. 37.5%) at 29 d after TAI, but CIDR inserts had no effect on pregnancy
      in experiment 2. Overall embryonic survival between 29 and 57 d in experiment 2
      was 57.7%. Use of CIDR inserts with Ovsynch improved conception and embryo
      survival in experiment 1 but not in experiment 2, in part due to differing
      proportions of cyclic cows at the outset. Presynchronization before Ovsynch
      enhanced pregnancy rate.

PMID- 15259239
TI  - Ruminal biohydrogenation in Holstein cows fed soybean fatty acids as amides or
      calcium salts.
AB  - Fatty amides of high oleate fats and calcium salts of palm oil were reported to
      resist biohydrogenation by ruminal microorganisms. This study was conducted to
      determine whether converting polyunsaturated fat sources to amides and calcium
      salts had equal ability to resist biohydrogenation. A total mixed ration
      consisting of forage and concentrate contained (dry basis): 1) 2.45% soybean oil
      (SBO), 2) 2.75% calcium salt of SBO, 3) 2.75% amide of SBO, or 4) 2.75% of a
      mixture of the calcium salt and amide (80:20, wt/wt) of SBO. The 4 diets were fed
      ad libitum to 4 multiparous lactating Holstein cows fitted with ruminal cannulas
      in a 4 x 4 Latin square with 21-d periods. Omasal samples were taken to measure
      postruminal fatty acid content and determine the extent of ruminal
      biohydrogenation. Adding SBO to the diets as either calcium salts or amides
      increased omasal flow of C18:2 (n-6) from 25 to 39 g/d. Omasal flow of C18:1
      increased from 36 to 49 g/d when SBO was fed to cows as calcium salts, but
      increased to 86 g/d when SBO was fed as amides. Adding the soybean amide to the
      diet more than doubled the delivery of C18:1 (n-9) to the omasum of lactating
      cows, but it also increased trans fatty acid production in the rumen accompanied
      by milk fat depression. In this study, calcium salts and amide derivatives of
      fatty acids were both effective in enhancing omasal flow of unsaturataed fatty
      acids in lactating dairy cows. Amides were more effective than calcium salts for
      increasing the postruminal flow of oleic acid.

PMID- 15259240
TI  - Short communication: docosahexaenoic acid promotes vaccenic acid accumulation in
      mixed ruminal cultures when incubated with linoleic acid.
AB  - Previous studies found that feeding dairy cows a blend of fish and soybean oils
      enhanced milk vaccenic acid (VA) and conjugated linoleic acid (CLA)
      concentrations more than when the oils were fed separately. In these studies, the
      authors concluded that a component in fish oil was stimulating ruminal VA
      production from other sources of unsaturated fatty acids; however, that component
      was not identified. The objective of this study was to determine whether
      docosahexaenoic acid (DHA), an omega-3 fatty acid (FA) in fish oil, is the active
      component that promotes trans-C18:1 FA, VA in particular, accumulation using
      cultures of mixed ruminal microorganisms. Treatments consisted of control,
      control plus 5 mg of DHA (DH), control plus 30 mg of soybean oil (SBO), and
      control plus 5 mg of DHA and 30 mg of SBO (DHSBO). Treatments were incubated in
      triplicate in 125-mL flasks, and 5 mL of culture contents was taken at 0 and 24 h
      for fatty acid analysis by gas-liquid chromatography. After 24 h of incubation,
      the level of trans-C18:1 FA (14.1 and 11.7 mg/culture) and VA (13.0 and 10.2
      mg/culture) increased more with added DHA than with added SBO, respectively.
      Combining DHA and SBO yielded higher quantities of trans-C18:1 FA (21.3
      mg/culture) and VA (19.8 mg/culture) in the cultures than either fat source
      alone. These data suggest that DHA is the component in fish oil that promotes VA
      accumulation when incubated with linoleic acid.

PMID- 15259241
TI  - Fat digestion in veal calves fed milk replacers low or high in calcium and
      containing either casein or soy protein isolate.
AB  - The hypothesis tested was that the inhibitory effect of dietary soy protein
      versus casein on fat digestion in veal calves would be smaller when diets were
      fed with high instead of low calcium content. Male calves, 1 wk of age, were fed
      1 of 4 experimental milk replacers in a 2 x 2 factorial design. There were 19
      animals per dietary group. The milk replacers contained either casein or soy
      protein isolate as variable protein source and were either low or high in
      calcium. Body weight gain was not significantly affected by the experimental
      diets. Soy protein isolate versus casein significantly reduced apparent fat
      digestibility. High versus low calcium intake also depressed fat digestion. The
      protein effect was smaller (2.9% units) for the high than the low calcium diets
      (3.6% units), but the interaction did not reach statistical significance. Soy
      protein isolate versus casein raised fecal bile acid excretion and so did high
      versus low calcium intake. The difference in bile acid excretion between the soy
      and casein containing diets was significantly greater for the high than low
      calcium diets. The absorption of phosphorus, calcium, and magnesium was higher
      for the casein diets than for the soy-containing diets. This study shows for the
      first time that soy protein isolate versus casein depressed fat digestion and
      raised fecal bile acid excretion in veal calves.

PMID- 15259242
TI  - Nitrogen balance, microbial protein production, and milk production in dairy cows
      fed fodder beets and potatoes, or barley.
AB  - Fourteen multiparous midlactation dairy cows were used in a change-over
      experiment with 3 periods and 3 diets to evaluate the effects of fodder beets and
      potatoes on N metabolism, microbial protein production, and milk production. A
      basal ration of alfalfa/grass silage offered ad libitum, 1 kg of grass hay and 1
      kg of heat-treated rapeseed cake was supplemented with 5 kg DM of either rolled
      barley/raw potatoes 80:20 (BAP), fodder beets/raw potatoes 80:20 (BEP) or rolled
      barley (BA). Urine and feces were collected quantitatively from 8 cows and
      ruminal samplings, and evacuations were performed on 4 cannulated cows. Intake
      and production did not differ between BAP and BA, but the BEP diet lowered intake
      of both silage and total ration by 0.9 kg DM. Daily yield of energy-corrected
      milk (ECM) was decreased by 1.7 and 2.3 kg compared with BAP and BA,
      respectively. Milk urea concentration was 1 mM lower with the BEP diet. The
      proportion of feed N recovered in milk was 20 to 21% for all diets. With the BEP
      diet, urinary N amount and proportion were reduced correspondingly to the lower
      total N intake. Fecal N amount remained unchanged, and hence nitrogen apparent
      digestibility decreased by 5 percentage units with the BEP diet. Microbial
      protein production, assessed by allantoin excretion, tended to be highest with
      the BAP diet. Acetate proportion of VFA was lowered by the BEP diet, while
      proportions of propionate and butyrate both tended to increase. Different
      fermentation patterns, probably related to differences in rumen microbiota, could
      explain why changes in energetic efficiency and milk composition reported in the
      literature did not occur in the actual experiment when roots replaced barley.
      Compared with barley, roots appeared to have a greater negative effect on silage
      intake in conjunction with a prewilted silage with high intake potential allowed
      ad libitum and this decreased milk production by a magnitude corresponding to the
      lower intake of ME.

PMID- 15259243
TI  - Feeding 2-hydroxy-4-(methylthio)-butanoic acid to periparturient dairy cows
      improves milk production but not hepatic metabolism.
AB  - Forty-eight Holstein cows, entering second or later lactation, were utilized to
      determine the effects of 2-hydroxy-4-(methylthio)-butanoic acid (HMB) on milk
      production, hepatic lipid metabolism, and gluconeogenesis during the
      periparturient period. Cows were fed one of 3 diets as TMR starting 21 d before
      expected calving. These diets contained 0 (the basal diet), 0.09 (+HMB), or 0.18
      (++HMB)% HMB. From parturition to 84 DIM, cows were fed diets that contained 0,
      0.13, or 0.20% HMB. Prepartum and postpartum dry matter intakes were similar
      among cows fed the basal diet, +HMB and ++HMB. There was a quadratic effect on
      milk yield such that cows fed +HMB had the greatest milk yield; yields of milk by
      cows fed the basal diet and ++HMB were similar. This led to trends for increased
      yields of 3.5% fat-corrected milk and total solids when cows were fed +HMB.
      Percentages of fat, protein, and total solids in milk were not affected by
      treatment. Despite differences in milk yield, calculated energy balance was not
      affected by treatment. Plasma concentrations of NEFA, beta-hydroxybutyrate, and
      glucose were not different among treatments. Liver triglyceride content was
      similar among treatments on d 1 postpartum and was increased for cows consuming
      +HMB on d 21 postpartum compared with the other dietary treatments. Capacities
      for metabolism of [1-14C]palmitate by liver slices in vitro were not affected by
      treatment; however, conversion of [1-14C]propionate to CO2 and glucose decreased
      as the amount of HMB consumed by cows increased on d 21 postpartum. Cows
      consuming +HMB had greater days to first ovulation compared with cows consuming
      the basal diet and ++HMB as measured by plasma progesterone concentrations. These
      data suggest that adding HMB to low Met diets to achieve a predicted Met supply
      of approximately 2.3% of metabolizable protein supply is beneficial for
      increasing milk production but does not appear to benefit hepatic energy
      metabolism during early lactation.

PMID- 15259244
TI  - Effect of zinc source and dietary level on zinc metabolism in Holstein calves.
AB  - Forty-eight Holstein male calves were stratified by origin and body weight and
      randomly assigned to one of 4 treatment groups. Dietary treatments were
      administered in 2 phases. In phase 1, treatment groups received the basal diet
      with no supplemental Zn (control), basal diet plus 20 mg of Zn/kg of DM as ZnSO4
      or Zn proteinate (ZnProt), or basal diet plus 20 mg of Zn/kg of DM with 50% of
      the Zn supplied from each source (ZnM) for 98 d. In phase 2, calves continued to
      receive the same Zn source fed in phase 1; however, half of the calves in each
      treatment group were randomly selected to receive 500 mg of Zn/kg of DM (HiZnSO4,
      HiZnProt, HiZnM) for 14 d. Gain, feed intake, and feed efficiency of calves were
      not affected by treatment in either phase of the experiment. Treatment had no
      affect on plasma Zn concentration or alkaline phosphatase activity in phase 1,
      but liver Zn concentration was greater in calves fed ZnSO4 than those fed ZnProt.
      In phase 2, plasma Zn was greater in calves fed HiZnProt and HiZnM than in those
      fed HiZnSO4. Liver Zn was greater in calves fed HiZnProt than in those fed
      HiZnSO4. Duodenal Zn concentrations were greater in calves supplemented with
      HiZnProt and HiZnM than those supplemented with HiZnSO4. Liver metallothionein
      was greater in calves that received 500 mg of Zn/kg than in calves that received
      20 mg of Zn/ kg, but was not affected by Zn source. Calves fed HiZnProt and HiZnM
      had greater kidney Zn concentrations than those fed HiZnSO4. Heart, spleen,
      testicular, and bone Zn concentrations were not affected by Zn source. Hoof wall
      samples contained nearly 3-fold greater Zn concentrations than hoof sole. Calves
      fed ZnSO4 had greater Zn concentration in hoof wall samples than those fed ZnM.
      Hoof sole Zn concentration was not affected by Zn source or concentration. Plasma
      and tissue Zn concentrations at harvest were generally similar in calves
      supplemented with 20 mg of Zn/kg from ZnSO4 or ZnProt. However, when supplemented
      at 500 mg of Zn/kg, ZnProt was absorbed to a greater extent than ZnSO4, based on
      higher plasma, liver, duodenal, and kidney Zn concentrations.

PMID- 15259245
TI  - A multivariate approach to modeling shapes of individual lactation curves in
      cattle.
AB  - Milk test-day records of 5728 lactations of Italian Simmental cows were analyzed
      with multivariate factor analysis in order to extract 2 common factors, whose
      scores were used as quantitative measures of 2 main features of lactation curve
      shape-i.e., the increasing rate of yield in the first part of lactation and the
      rate of decline of milk yield after the lactation peak. The 2 indices,
      objectively derived from the correlation matrix of original test-day records,
      showed a high discriminant power in separating lactation curves with different
      shapes. The weak correlation between the 2 factors (0.11), together with the high
      correlation of factors and the total 305-d yield (about 0.70), suggests that an
      increase in lactation yield could be achieved by acting only on one of the 2
      factors related to lactation-curve shape, with the other kept constant at a
      medium or low value. The suitability of the 2 factors as descriptors of lactation
      patterns has been confirmed by the relationships found between factor scores and
      the main environmental effects known to affect the shape of the lactation curve,
      such as parity and season of calving.

PMID- 15259246
TI  - Electrical conductivity of milk: ability to predict mastitis status.
AB  - Electrical conductivity (EC) of milk has been introduced as an indicator trait
      for mastitis over the last decade, and it may be considered as a potential trait
      in a breeding program where selection for improved udder health is included. In
      this study, various EC traits were investigated for their association with udder
      health. In total, 322 cows with 549 lactations were included in the study. Cows
      were classified as healthy or clinically or subclinically infected, and EC was
      measured repeatedly during milking on each quarter. Four EC traits were defined;
      the inter-quarter ratio (IQR) between the highest and lowest quarter EC values,
      the maximum EC level for a cow, IQR between the highest and lowest quarter EC
      variation, and the maximum EC variation for a cow. Values for the traits were
      calculated for every milking throughout the entire lactation. All EC traits
      increased significantly (P < 0.001) when cows were subclinically or clinically
      infected. A simple threshold test and discriminant function analysis was used to
      validate the ability of the EC traits to distinguish between cows in different
      health groups. Traits reflecting the level rather than variation of EC, and in
      particular the IQR, performed best to classify cows correctly. By using this
      trait, 80.6% of clinical and 45.0% of subclinical cases were classified
      correctly. Of the cows classified as healthy, 74.8% were classified correctly.
      However, some extra information about udder health status was obtained when a
      combination of EC traits was used.

PMID- 15259247
TI  - Phenotypic and genetic influences on test-day measures of acetone concentration
      in milk.
AB  - The objectives of this study were to estimate heritability of acetone
      concentration in milk, based on monthly samples of milk obtained as part of a
      routine milk testing program, and to evaluate the feasibility of using such data
      in a genetic evaluation program for selection against ketosis incidence. Milk
      samples were collected from January to December of 1999 in herds enrolled in the
      Ontario Dairy Herd Improvement Association, and acetone concentration was
      measured using an inline chemical procedure. The original data included more than
      50,000 records. Because ketosis is generally a problem during early lactation,
      only the single test with the fewest days in milk was retained. In addition, data
      were retained only for cows with pedigree information. The final data set
      included 10,375 records. Among these data, only 6.56% had detectable levels of
      acetone. Acetone data were log-transformed prior to statistical analysis. Simple
      ANOVA indicated that herd, parity number, days in milk, and month of test had
      significant effects on acetone concentration. Acetone levels increased with
      lactation number and were higher in early lactation. Three approaches were
      applied for genetic analysis. First, REML was used with a simple linear animal
      model. Then, a separate procedure used data augmentation and Gibbs Sampling to
      obtain continuously distributed underlying values for records with zero acetone
      concentration, and these data were analyzed with both an animal and sire model.
      Heritability of acetone concentration was less than 1% for all 3 analyses. Herd
      effects accounted for about 5% of the phenotypic variance. Low estimates of
      heritability were due either to low actual levels of genetic variance or
      inability to detect all of the genetic variance present, due to infrequent
      recording during the early part of the lactation. Genetic evaluation based on
      recording of acetone concentration on a monthly basis seems of little use as a
      selection tool to decrease incidence of ketosis.

PMID- 15259248
TI  - The survival of foot-and-mouth disease virus in raw and pasteurized milk and milk
      products.
AB  - The Foot-and-Mouth Disease virus (FMDV) is not a public health threat, but it is
      highly contagious to cloven-footed animals. The virus is shed into milk up to 33
      h before there are apparent signs of the disease in dairy cows, and, in extreme
      cases, signs of disease may not appear for up to 14 d. During this time, raw milk
      can serve as a vector for spread of the disease both at the farm and during
      transport to the processing plant by milk tanker. Raw milk and milk products fed
      to animals have the potential to cause infection, but the potential for
      pasteurized milk products to cause infection is largely unknown. Current minimum
      pasteurization standards may not be adequate to eliminate FMDV in milk
      completely. The purpose of this paper is to assess the literature on the thermal
      resistance of FMDV in milk and milk products, to identify the risks associated
      with ingestion of pasteurized products by animals, and to lay a strategy to
      prevent the spread of FMDV from contaminated milk.

PMID- 15259249
TI  - Road safety is no accident: a call for global action.

PMID- 15259250
TI  - Global strengthening of care for the injured.

PMID- 15259251
TI  - Avian influenza and influenza pandemics.

PMID- 15259252
TI  - Use of medicinal plants and pharmaceuticals by indigenous communities in the
      Bolivian Andes and Amazon.
AB  - OBJECTIVE: To investigate, by means of household surveys, the use of medicinal
      plants and pharmaceuticals in Apillapampa, a large Andean community of Quechua
      peasants, and in six small communities of Yuracare-Trinitario "slash-and-burn"
      cultivators of the National Park Isiboro-Secure (the NPIS) in the Bolivian
      Amazon. METHODS: A total of 12% of households in Apillapampa and nearly all
      households in the NPIS were interviewed about their use of medicinal plants and
      pharmaceuticals for treating illnesses. Informants were also asked to name any
      medicinal plants they knew. FINDINGS: In spite of the presence of a primary
      health care service (PHC) with medical doctor in Apillapampa, an equal number of
      informants used medicinal plants and pharmaceuticals. In the NPIS, the prevalent
      use of medicinal plants or pharmaceuticals in any community depended on the
      distance of the community from the nearest village and from a PHC with medical
      doctor (r = 0.85 and r = -0.96; both P = 0.05. The NPIS communities' knowledge of
      plants expressed as the average number of medicinal plants mentioned correlated
      positively and negatively with distance from the nearest village and use of
      pharmaceuticals, respectively (r= 0.95, P < 0.005 and r = -0.90, P < 0.05,
      respectively). CONCLUSION: The cultural importance of traditional medicine and
      the physical isolation of communities, both in general and from PHCs, are factors
      that influence the use of and knowledge about medicinal plants.

PMID- 15259253
TI  - Current and future worldwide prevalence of dependency, its relationship to total
      population, and dependency ratios.
AB  - OBJECTIVE: To estimate the number of people worldwide requiring daily assistance
      from another person in carrying out health, domestic or personal tasks. METHODS:
      Data from the Global Burden of Disease Study were used to calculate the
      prevalence of severe levels of disability, and consequently, to estimate
      dependency. Population projections were used to forecast changes over the next 50
      years. FINDINGS: The greatest burden of dependency currently falls in sub-Saharan
      Africa, where the "dependency ratio" (ratio of dependent people to the population
      of working age) is about 10%, compared with 7-8% elsewhere. Large increases in
      prevalence are predicted in sub-Saharan Africa, the Middle East, Asia and Latin
      America of up to 5-fold or 6-fold in some cases. These increases will occur in
      the context of generally increasing populations, and dependency ratios will
      increase modestly to about 10%. The dependency ratio will increase more in China
      (14%) and India (12%) than in other areas with large prevalence increases.
      Established market economies, especially Europe and Japan, will experience modest
      increases in the prevalence of dependency (30%), and in the dependency ratio (up
      to 10%). Former Socialist economies of Europe will have static or declining
      numbers of dependent people, but will have large increases in the dependency
      ratio (up to 13%). CONCLUSION: Many countries will be greatly affected by the
      increasing number of dependent people and will need to identify the human and
      financial resources to support them. Much improved collection of data on
      disability and on the needs of caregivers is required. The prevention of
      disability and provision of support for caregivers needs greater priority.

PMID- 15259254
TI  - Rubella serosurveys at three Aravind Eye Hospitals in Tamil Nadu, India.
AB  - OBJECTIVE: To determine the susceptibility of female eye hospital staff to
      rubella infection and the potential risk for hospital-based rubella outbreaks.
      METHODS: A prospective cohort study on the seroprevalence of rubella IgG
      antibodies was conducted at three large eye hospitals in Coimbatore, Madurai and
      Tirunelveli, Tamil Nadu, India, where young children with eye abnormalities
      attributable to congenital rubella are treated. A total of 1000 female hospital
      employees aged 18-40 years agreed to participate and gave written informed
      consent. FINDINGS: The proportions of rubella-seronegative women were: 11.7% at
      Coimbatore, with a 95% confidence interval (CI) of 8.1-16.5; 15% at Madurai (95%
      CI = 12.3-18.1), and 20.8 at Tirunelveli (95% CI = 14.7-28.6). For the entire
      cohort the proportion seronegative was significantly higher among married women
      (21.5%) than among single women (14.0%) (P = 0.02). Rates of seronegativity were
      highest among physicians and lowest among housekeepers. All 150 seronegative
      women in the study sample accepted a dose of rubella vaccine. CONCLUSION: These
      are the first rubella serosurveys to have been reported from eye hospitals in any
      country. The relatively high rate of susceptibility indicated a risk of a rubella
      outbreak, and this was reduced by vaccinating all seronegative women. A policy
      has been established at all three hospitals for the provision of rubella vaccine
      to new employees. Other hospitals, especially eye hospitals and hospitals in
      countries without routine rubella immunization, should consider the rubella
      susceptibility of staff and the risk of hospital-based rubella outbreaks.

PMID- 15259255
TI  - Risk factors of infant and child mortality in rural Burkina Faso.
AB  - OBJECTIVE: The aim of the study was to quantify the effect of risk factors for
      childhood mortality in a typical rural setting in sub-Saharan Africa. METHODS: We
      performed a survival analysis of births within a population under demographic
      surveillance from 1992 to 1999 based on data from a demographic surveillance
      system in 39 villages around Nouna, western Burkina Faso, with a total population
      of about 30000. All children born alive in the period 1 January 1993 to 31
      December 1999 in the study area (n = 10 122) followed-up until 31 December 1999
      were included. All-cause childhood mortality was used as outcome variable.
      FINDINGS: Within the observation time, 1340 deaths were recorded. In a Cox
      regression model a simultaneous estimation of hazard rate ratios showed death of
      the mother and being a twin as the strongest risk factors for mortality. For
      both, the risk was most pronounced in infancy. Further factors associated with
      mortality include age of the mother, birth spacing, season of birth, village,
      ethnic group, and distance to the nearest health centre. Finally, there was an
      overall decrease in childhood mortality over the years 1993-99. CONCLUSION: The
      study supports the multi-causation of childhood deaths in rural West Africa
      during the 1990s and supports the overall trend, as observed in other studies, of
      decreasing childhood mortality in these populations. The observed correlation
      between the factors highlights the need for multivariate analysis to disentangle
      the separate effects. These findings illustrate the need for more comprehensive
      improvement of prenatal and postnatal care in rural sub-Saharan Africa.

PMID- 15259256
TI  - Do family-planning workers in China support provision of sexual and reproductive
      health services to unmarried young people?
AB  - OBJECTIVE: To ascertain the perspectives of family-planning service providers in
      eight sites in China on the provision of sexual and reproductive health services
      to unmarried young people. METHODS: Data were drawn from a survey of 1927 family
      planning workers and 16 focus group discussions conducted in eight sites in China
      in 1998-99. FINDINGS: Family-planning workers recognized the need to protect the
      sexual health of unmarried young people and were unambiguous about the need for
      government agencies to provide information and education on sexual and
      reproductive health to unmarried young people; however, perceptions about the
      appropriate age for and content of such education remained conservative. While
      about 70% of family-planning workers were willing to provide contraceptives to
      unmarried young people, and about 60% approved government provision of
      contraceptive services to unmarried young people, only one quarter agreed that
      the services could be extended to senior high schools. CONCLUSION: Family
      planning workers in China are ambivalent about the provision of sexual and
      reproductive health services to unmarried young people, which potentially poses a
      significant obstacle to the adoption of safe sex behaviours by young people, as
      well as to the provision of sexual and reproductive health information and
      services to young unmarried people in China. Training programmes for family
      planning workers are urgently needed to address this issue.

PMID- 15259257
TI  - Cost effectiveness of a latrine revision programme in Kabul, Afghanistan.
AB  - INTRODUCTION: We assessed a household latrine revision intervention implemented
      in Kabul, Afghanistan for evidence of a reduction in diarrhoeal disease. METHODS:
      A case-control design involving 1238 cases and 625 controls was used. Logistic
      regression modelling was performed both for children < 5 years and < or = 11
      years, and the parameter estimates were later used with results from a stratified
      cluster sample survey. This survey used a verbal autopsy methodology to enable an
      estimation of the number of deaths averted over a 1-year period. A cost
      effectiveness analysis using direct and indirect costs for the intervention was
      then conducted and the results compared with primary health care interventions
      identified from a Medline search. FINDINGS: Conditional logistic regression
      showed that patients were less likely than controls to live in households with
      revised latrines (odds ratio (OR) 0.57, 95% confidence interval (CI) = 0.42-0.77
      for children < 5 years, and OR 0.53, 95% = CI 0.41-0.67 for children < or = 11
      years). The results from the survey of cause-specific mortality by verbal autopsy
      enabled estimation of the number of deaths averted over a 1-year period due to
      the intervention; these estimations were 235 (95% CI = 109-360) for children < 5
      years and 285 (95% CI = 180-397) for children < or = 11 years. Estimates of cost
      effectiveness ranged from approximately US dollars 1800 to US dollars 4100 per
      death averted depending on age and payer perspective. CONCLUSION: These estimates
      are conservative because only 1 year of effectiveness is considered, yet they
      compare favourably with a review of other paediatric interventions. These results
      are important because funding for sanitation interventions is often limited by
      the belief that the interventions are not cost-effective.

PMID- 15259258
TI  - Reconsidering empirical cotrimoxazole prophylaxis for infants exposed to HIV
      infection.
AB  - Infants with HIV infection are vulnerable to Pneumocystis carinii pneumonia (PCP)
      during their first year of life. WHO and the Joint United Nations Programme on
      HIV/AIDS now recommend that all children of HIV-positive mothers receive
      prophylactic cotrimoxazole against PCP from six weeks of age and continue this
      therapy until exposure through breast milk ceases-and the infant is confirmed to
      be HIV-negative (rarely before one year of age). Empirical prophylaxis invokes a
      trade-off between possible benefit to the infant versus the risk of resistance to
      antibiotics and antimalarials. From a critical analysis of the literature, we
      offer a conceptual model demonstrating how, under certain circumstances, a policy
      of mass cotrimoxazole prophylaxis may be counterproductive.

PMID- 15259259
TI  - Cotrimoxazole prophylaxis for infants exposed to HIV infection.

PMID- 15259260
TI  - Rates, barriers and outcomes of HIV serostatus disclosure among women in
      developing countries: implications for prevention of mother-to-child transmission
      programmes.
AB  - This paper synthesizes the rates, barriers, and outcomes of HIV serostatus
      disclosure among women in developing countries. We identified 17 studies from
      peer-reviewed journals and international conference abstracts--15 from sub
      Saharan Africa and 2 from south-east Asia--that included information on either
      the rates, barriers or outcomes of HIV serostatus disclosure among women in
      developing countries. The rates of disclosure reported in these studies ranged
      from 16.7% to 86%, with women attending free-standing voluntary HIV testing and
      counselling clinics more likely to disclose their HIV status to their sexual
      partners than women who were tested in the context of their antenatal care.
      Barriers to disclosure identified by the women included fear of accusations of
      infidelity, abandonment, discrimination and violence. Between 3.5% and 14.6% of
      women reported experiencing a violent reaction from a partner following
      disclosure. The low rates of HIV serostatus disclosure reported among women in
      antenatal settings have several implications for prevention of mother-to-child
      transmission of HIV (pMTCT) programmes as the optimal uptake and adherence to
      such programmes is difficult for women whose partners are either unaware or not
      supportive of their participation. This article discusses these implications and
      offers some strategies for safely increasing the rates of HIV status disclosure
      among women.

PMID- 15259261
TI  - EU faces world's fastest growing HIV epidemic.

PMID- 15259262
TI  - Clinical trials without ethical review under the spotlight.

PMID- 15259263
TI  - Growing road traffic death toll requires action from all sectors, urges new
      report.

PMID- 15259264
TI  - Viral abundance and a high proportion of lysogens suggest that viruses are
      important members of the microbial community in the Gulf of Trieste.
AB  - Epifluorescence microscopy and transmission electron microscopy were applied to
      study virioplankton community in the Gulf of Trieste (northern Adriatic Sea). The
      total viral abundance was in a range between 2.5 x 10(9)/L and 2.9 x 10(10)/L and
      was positively correlated with trophic status of the environment. Viruslike
      particles were significantly correlated with bacterial abundance in all samples
      studied. Correlations with other physicochemical or biological parameters were
      not significant. The data suggest that, because of the substantial fraction of
      tailed viruses present (26%), bacteriophages are an important component of the
      virioplankton community in the Gulf of Trieste. The abundance of viruslike
      particles in the seawater changed at hour intervals in a range from 1.3 x 10(9)/L
      to 5.1 x 10(9)/L. A significant fraction (71%) of the bacterial isolates was
      inducible in vitro by mitomycin C, and a high occurrence (51%) of lysogenic
      isolates with more than one phage morphotype present in the lysate was detected.
      The presence of lysogenic bacteria in the seawater was confirmed in situ with a
      mitomycin C induction experiment on the natural bacterial population. Results
      suggest that virioplankton is an abundant component of the microbial community in
      the Gulf of Trieste.

PMID- 15259265
TI  - Abundance, distribution, and diversity of viruses in alkaline, hypersaline Mono
      Lake, California.
AB  - Mono Lake is a large (180 km2), alkaline (pH approximately 10), moderately
      hypersaline (70-85 g kg(-1)) lake lying at the western edge of the Great Basin.
      An episode of persistent chemical stratification (meromixis) was initiated in
      1995 and has resulted in depletion of oxygen and accumulation of ammonia and
      sulfide beneath the chemocline. Although previous studies have documented high
      bacterial abundances and marked seasonal changes in phytoplankton abundance and
      community composition, there have been no previous reports on the occurrence of
      viruses in this unique lake. Based on the high concentrations and diversity of
      microbial life in this lake, we hypothesized that planktonic viruses are also
      abundant and diverse. To examine the abundance and distribution of viruses and
      bacteria, water samples were collected from four stations along 5 to 15 vertical
      depths at each station. Viral abundance ranged from 1 x 10(8) to 1 x 10(9) mL(
      1), among the highest observed in any natural aquatic system examined so far.
      Increases (p < 0.1) in viral densities were observed in the anoxic bottom water
      at multiple stations. However, regression analysis indicated that viral abundance
      could not be predicted by any single environmental parameter. Pulsed field gel
      electrophoresis revealed a diverse viral community in Mono Lake with genome sizes
      ranging from approximately 14 to >400 kb with most of the DNA in the 30 to 60 kb
      size range. Cluster analysis grouped the anoxic bottom-water viral community into
      a unique cluster differentiating it from surface and mid-water viral communities.
      A hybridization study using an indigenous viral isolate as a probe revealed an
      episodic pattern of temporal phage distribution with strong niche stratification
      between oxic and anoxic waters.

PMID- 15259266
TI  - Quantitative importance, composition, and seasonal dynamics of protozoan
      communities in polyhaline versus freshwater intertidal sediments.
AB  - The quantitative importance and composition of protozoan communities was
      investigated in sandy and silty intertidal sediments of a polyhaline and a
      freshwater site in the Schelde estuary. Total biomass of the protozoans studied,
      integrated over the upper 4 cm of the sediment, ranged from 41 to 597 mg C m(-2)
      and was in the same order of magnitude at the polyhaline and the freshwater
      intertidal site. Nanoheterotrophs were the dominant protozoans, in terms of both
      abundance and biomass. Ciliate abundances appeared to be largely determined by
      physical constraints, namely, the amount of interstitial space and hydrodynamic
      disturbances. It remains unclear which factors control nanoheterotrophic
      abundances and biomasses, which showed comparatively little seasonal and between
      site fluctuations. Salinity differences were clearly reflected in the protozoan
      community composition. The dominant role of sessile ciliates is a unique feature
      of sediments in the freshwater tidal reaches, which can be attributed to the
      dynamic nature of sedimentation and resuspension processes associated with the
      maximum turbidity zone. Based on biomass ratios and estimated weight-specific
      metabolic rates, protozoa possibly accounted for approximately 29 to 96% of the
      estimated combined metabolic rate of protozoan and metazoan consumers at our
      sampling stations in late spring/early autumn. The contribution of protozoa to
      this combined metabolic rate was higher at the sandy than at the silty stations
      and was mainly accounted for by the nanoheterotrophs. These data emphasize the
      potential importance of small protozoa in sediments and suggest that protozoa are
      important components of benthic food webs.

PMID- 15259267
TI  - Vertical distribution of nitrogen-fixing phylotypes in a meromictic, hypersaline
      lake.
AB  - We investigated the diversity of nitrogenase genes in the alkaline, moderately
      hypersaline Mono Lake, California to determine (1) whether nitrogen-fixing
      (diazotrophic) populations were similar to those in other aquatic environments
      and (2) if there was a pattern of distribution of phylotypes that reflected redox
      conditions, as well as (3) to identify populations that could be important in N
      dynamics in this nitrogen-limited lake. Mono Lake has been meromictic for almost
      a decade and has steep gradients in oxygen and reduced compounds that provide a
      wide range of aerobic and anaerobic habitats. We amplified a fragment of the
      nitrogenase gene (nifH) from planktonic DNA samples collected at three depths
      representing oxygenated surface waters, the oxycline, and anoxic, ammonium-rich
      deep waters. Forty-three percent of the 90 sequences grouped in nifH Cluster I.
      The majority of clones (57%) grouped in Cluster III, which contains many known
      anaerobic bacteria. Cluster I and Cluster III sequences were retrieved at every
      depth indicating little vertical zonation in sequence types related to the
      prominent gradients in oxygen and ammonia. One group in Cluster I was found most
      often at every depth and accounted for 29% of all the clones. These sequences
      formed a subcluster that contained other environmental clones, but no cultivated
      representatives. No significant nitrogen fixation was detected by the 15N2 method
      after 48 h of incubation of surface, oxycline, or deep waters, suggesting that
      pelagic diazotrophs were contributing little to nitrogen fluxes in the lake. The
      failure to measure any significant nitrogen fixation, despite the detection of
      diverse and novel nitrogenase genes throughout the water column, raises
      interesting questions about the ecological controls on diazotrophy in Mono Lake
      and the distribution of functional genes in the environment.

PMID- 15259268
TI  - Pseudomonas aeruginosa isolated from marine environments in Tokyo Bay.
AB  - Pseudomonas aeruginosa is a pathogenic bacterium that has been thoroughly
      investigated since the 19th century and is generally regarded as a freshwater or
      terrestrial organism. In 1995, it was reported that the OprP porin, an outer
      membrane protein corresponding to that of this bacterium, was widely distributed
      as a dissolved component in seawater. This finding led us to investigate the
      presence of P. aeruginosa in marine environments. Both culture-independent and 
      dependent methods were applied to seawater samples obtained in Tokyo Bay during
      four cruises. The DVC-FA (direct viable count-fluorescent antibody) technique
      showed that cells reactive to an antibody against P. aeruginosa were widely
      present in the bay, i.e., 10(3) to 10(4) cells/mL in the inner bay, and 10(2) to
      10(3) cells/mL at the mouth. Bacterial cells isolated by selective medium were
      identified by three methods: the presence of oprI and oprL, two outer membrane
      lipoprotein genes specific to P. aeruginosa; the API20 NE kit; and 16S rDNA
      sequence analysis. The results confirmed that the majority of isolates from the
      bay were P. aeruginosa. Immuno-chemical analyses of the seawater results indicate
      that P. aeruginosa is commonly present in coastal marine environments and sheds
      OprP.

PMID- 15259269
TI  - Predator/prey interaction between Pfiesteria piscicida and Rhodomonas mediated by
      a marine alpha proteobacterium.
AB  - The dinoflagellate Pfiesteria piscicida coexists with bacteria in aquatic
      environments and as such, may interact with them at the physiological level. This
      study was designed to investigate the influence of bacteria, present in a clonal
      culture of Pfiesteria piscicida, on the predator/prey relationship of this
      dinoflagellate with the alga Rhodomonas. A series of replenishment experiments
      with bacteria isolated from P. piscicida clonal culture and the bacteria-free P.
      piscicida derived from the same culture were carried out. In the presence of
      bacteria, the number of P. piscicida increased significantly when incubated with
      alga Rhodomonas. This enhanced growth was almost entirely due to the increased
      consumption rate of Rhodomonas by P. piscicida since in bacteria-free (axenic)
      cultures Rhodomonas were consumed at significantly reduced rates relative to
      cultures with bacteria. Subsequent replenishment experiments with individual
      bacterial isolates showed that a single isolate was responsible for the increased
      predation rate of P. piscicida. The presence or absence of this specific
      bacterium determined the outcome of the interaction between P. piscicida and
      Rhodomonas. Partial sequence analysis of the 16S rDNA of this isolate indicated
      that it was a novel marine alpha proteobacterium with sequence similarities to a
      Roseobacter sp. and a bacterium recently isolated from a toxic dinoflagellate
      Alexandrium sp.

PMID- 15259270
TI  - Archaeal community structure and pathway of methane formation on rice roots.
AB  - The community structure of methanogenic Archaea on anoxically incubated rice
      roots was investigated by amplification, sequencing, and phylogenetic analysis of
      16S rRNA and methyl-coenzyme M reductase (mcrA) genes. Both genes demonstrated
      the presence of Methanomicrobiaceae, Methanobacteriaceae, Methanosarcinaceae,
      Methanosaetaceae, and Rice cluster I, an uncultured methanogenic lineage. The
      pathway of CH4 formation was determined from the 13C-isotopic signatures of the
      produced CH4, CO2 and acetate. Conditions and duration of incubation clearly
      affected the methanogenic community structure and the pathway of CH4 formation.
      Methane was initially produced from reduction of CO2 exclusively, resulting in
      accumulation of millimolar concentrations of acetate. Simultaneously, the
      relative abundance of the acetoclastic methanogens (Methanosarcinaceae,
      Methanosaetaceae), as determined by T-RFLP analysis of 16S rRNA genes, was low
      during the initial phase of CH4 production. Later on, however, acetate was
      converted to CH4 so that about 40% of the produced CH4 originated from acetate.
      Most striking was the observed relative increase of a population of
      Methanosarcina spp. (but not of Methanosaeta spp.) briefly before acetate
      concentrations started to decrease. Both acetoclastic methanogenesis and
      Methanosarcina populations were suppressed by high phosphate concentrations, as
      observed under application of different buffer systems. Our results demonstrate
      the parallel change of microbial community structure and function in a complex
      environment, i.e., the increase of acetoclastic Methanosarcina spp. when high
      acetate concentrations become available.

PMID- 15259272
TI  - Impact of clay minerals on sulfate-reducing activity in aquifers.
AB  - Previous studies have shown that sulfate-reduction activity occurs in a
      heterogeneous manner throughout the terrestrial subsurface. Low-activity regions
      are often observed in the presence of clay minerals. Here we report that clays
      inhibit sulfate reduction activity in sediments and in a pure culture of
      Desulfovibrio vulgaris. Clay minerals including bentonite and kaolinite inhibited
      sulfate reduction by 70-90% in sediments. Intact clays and clay colloids or
      soluble components, capable of passing through a 0.2-microm filter, were also
      inhibitory to sulfate-reducing bacteria. Other adsorbent materials, including
      anion or cation exchangers and a zeolite, did not inhibit sulfate reduction in
      sediments, suggesting that the effect of clays was not due to their cation
      exchange capacity. We observed a strong correlation between the Al2O3 content of
      clays and their relative ability to inhibit sulfate reduction in sediments (r2 =
      0.82). This suggested that inhibition might be a direct effect of Al3+ (aq) on
      the bacteria. We then tested pure aluminum oxide (Al2O3) and showed it to act in
      a similar manner to clay. As dissolved aluminum is known to be toxic to a variety
      of organisms at low concentrations, our results suggest that the effects of clay
      on sulfate-reducing bacteria may be directly due to aluminum. Thus, our
      experiments provide an explanation for the lack of sulfate-reduction activity in
      clay-rich regions and presents a mechanism for the effect.

PMID- 15259271
TI  - Analysis of diversity among 3-chlorobenzoate-degrading strains of
      Rhodopseudomonas palustris.
AB  - The phenotypic and genetic characteristics of 14 strains of the purple nonsulfur
      bacterium Rhodopseudomonas palustris were studied to assess diversity within this
      species. While all strains had certain phenotypic characteristics in common,
      including the ability to metabolize benzoate and degrade 2- and 3-chlorobenzoate,
      there were also significant differences among the strains such as the rate of
      growth in media containing benzoate as a carbon source. Genetic characterization
      of the strains revealed there were three divergent lineages in the species. Based
      on 16S rRNA gene sequences, the 14 strains could be grouped into three distinct
      clusters (A, B, and C), and this clustering was congruent with that based on gene
      sequences of form II ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO).
      Although BOX-PCR genomic DNA fingerprints of all 14 strains exhibited
      differences, analysis of the fingerprint images and UPGMA/product-moment analysis
      of similarities showed there were three groupings that were entirely consistent
      with clusters based on other characteristics of the strains. Thus, regardless of
      the method of analysis used, strains in groups A and B consistently clustered
      together and were separate from those of group C. These results suggest that
      strains in groups A-B and C represent phylogenetically related clones that have
      diverged from one another. This indicates that at least three lineages of
      Rhodopseudomonas palustris exist among the strains included in this study, and
      that each may be particularly well adapted to a distinct ecological niche.

PMID- 15259273
TI  - Comparison of the phenotypes and genotypes of biofilm and solitary epiphytic
      bacterial populations on broad-leaved endive.
AB  - The discovery that biofilms are ubiquitous among the epiphytic microflora of
      leaves has prompted research about the impact of biofilms on the ecology of
      epiphytic microorganisms and on the efficiency of strategies to manage these
      populations for disease control and to ensure food safety. Biofilms are likely to
      influence the microenvironment and phenotype of the microorganisms they harbor.
      However, it is also important to determine whether there are differences in the
      types of bacteria within biofilms compared to those outside of biofilms so as to
      better target microorganisms via disease control strategies. Broad-leaved endive
      (Cichorium endivia var. latifolia) harbors biofilms containing fluorescent
      pseudomonads. These bacteria can cause considerable post-harvest losses when this
      plant is used for manufacturing minimally processed salads. To determine whether
      the population structure of the fluorescent pseudomonads in biofilms is different
      from that outside of biofilms on the same leaves, bacteria were isolated
      quantitatively from the biofilm and solitary components of the epiphytic
      population on leaves of field-grown broad-leaved endive. Population structure was
      determined in terms of taxonomic identities of the bacteria isolated, in terms of
      genotypic profiles, and in terms of phenotypic traits related to surface
      colonization and biofilm formation. The results illustrate that there are no
      systematic differences in the composition and structure of biofilm and solitary
      populations of fluorescent pseudomonads, in terms of either genotypic profiles or
      phenotypic profiles of the strains. However, Gram-positive bacteria tended to
      occur more frequently within biofilms than outside of biofilms. We suggest that
      leaf colonization by fluorescent pseudomonads involves a flux of cells between
      biofilm and solitary states. This would allow bacteria to exploit the advantages
      of these two types of existence; biofilms would favor resistance to stressful
      conditions, whereas solitary cells could foster spread of bacteria to newly
      colonizable sites on leaves as environmental conditions fluctuate.

PMID- 15259274
TI  - Engineering root exudation of Lotus toward the production of two novel carbon
      compounds leads to the selection of distinct microbial populations in the
      rhizosphere.
AB  - The culture of opine-producing transgenic Lotus plants induces the increase in
      the rhizosphere of bacterial communities that are able to utilize these molecules
      as sole carbon source. We used transgenic Lotus plants producing two opines,
      namely mannopine and nopaline, to characterize the microbial communities directly
      influenced by the modification of root exudation. We showed that opine-utilizers
      represent a large community in the rhizosphere of opine-producing transgenic
      Lotus. This community is composed of at least 12 different bacterial species, one
      third of which are able to utilize the opine mannopine and two thirds the opine
      nopaline. Opine utilizers are diverse, belonging to the Gram-positive and 
      negative bacteria. We described two novel mannopine-utilizing species, Rhizobium
      and Duganella spp., and five novel nopaline-utilizing species, Duganella, Afipia,
      Phyllobacterium, Arthrobacter, and Bosea spp. Although opine utilizers mostly
      belong to the alpha-Proteobacteria, Rhizobiaceae family, there is little overlap
      between the populations able to utilize each of the two opines produced by the
      plants. Noticeably, in the rhizosphere of transgenic Lotus, only the opine
      mannopine favors the growth of Agrobacterium tumefaciens, the bacterium from
      which opines have been characterized. The diversity of opine utilizers from the
      rhizosphere of Lotus plants is greater than that observed from any other
      environment. Therefore, transgenic plants with engineered exudation constitute an
      excellent tool to isolate and characterize specific microbial populations.

PMID- 15259275
TI  - The relationship between microbial community structure and functional stability,
      tested experimentally in an upland pasture soil.
AB  - Soil collected from an upland pasture was manipulated experimentally in ways
      shown previously to alter microbial community structure. One set of soil was
      subjected to chloroform fumigation for 0, 0.5, 2, or 24 h and the other was
      sterilised by gamma-irradiation and inoculated with a 10(-2), 10(-4), 10(-6), or
      10(-8) dilution of a soil suspension prepared from unsterilized soil. Following
      incubation for 8 months, to allow for the stabilization of microbial biomass and
      activity, the resulting microbial community structure (determined by PCR-DGGE of
      bacterial specific amplification products of total soil DNA) was assessed. In
      addition, the functional stability (defined here as the resistance and resilience
      of short-term decomposition of plant residues to a transient heat or a persistent
      copper perturbation) was determined. Changes in the active bacterial population
      following perturbation (determined by RT-PCR-DGGE of total soil RNA) were also
      monitored. The manipulations resulted in distinct shifts in microbial community
      structure as shown by PCR-DGGE profiles, but no significant decreases in the
      number of bands. These shifts in microbial community structure were associated
      with a reduction in functional stability. The clear correlation between altered
      microbial community structure and functional stability observed in this upland
      pasture soil was not evident when the same protocols were applied to soils in
      other studies. RT-PCR-DGGE profiles only detected a shift in the active bacterial
      population following heat, but not copper, perturbation. We conclude that the
      functional stability of decomposition is related to specific components of the
      microbial community.

PMID- 15259276
TI  - Should epidemiology, the media and quangos determine clinical practice?

PMID- 15259277
TI  - The Million Women Study: potential biases do not allow uncritical acceptance of
      the data.
AB  - BACKGROUND: The findings in the Million Women Study (MWS) have been interpreted
      by some as providing final and definitive evidence that hormone therapy (HT)
      (estrogen alone or estrogen plus a progestin) increases the risk of breast
      cancer. METHODS: A critical review of the MWS evidence. CRITIQUE: It is
      established that women who attend for routine mammography are not representative
      of the population at large: HT is more common among attenders, as is the
      occurrence of breast cancer. The MWS cohort comprised women who were invited to
      enroll when they were scheduled for mammography. Especially in that setting, HT
      users could more commonly have enrolled because of enhanced anxiety about breast
      cancer risk, women already aware of breast lumps could also selectively have
      enrolled--and women who both used HT, and who were aware of breast lumps, could
      have been the most motivated to participate. Thus, it was possible that the
      selective detection of as yet undiagnosed breast cancer among HT users could have
      accounted for the small associations between HT and breast cancer observed. The
      data supported that possibility. The incidence of breast cancer at or soon after
      recruitment was higher than in the population at large; HT was more common than
      in the population at large; the time intervals from recruitment to the diagnosis
      of breast cancer, or death, were implausibly short; and, in clinical and
      pathological terms, discordance in the risk of breast cancer among current users
      of HT, and among those who had recently stopped could most plausibly be explained
      by detection bias. Additional defects in the MWS, pointed in correspondence,
      included failure to properly specify zero time; and failure to record
      discontinued HT use or cross-overs, with resultant misclassification of the time,
      type, and duration of HT. The MWS report also contained multiple errors-
      sufficient to raise doubts about the care with which the study was carried out,
      and reviewed. Finally, findings in the MWS were discordant with those reported in
      other studies. CONCLUSIONS: Based on the MWS findings, it is not possible to
      distinguish between bias and causation as alternative explanations for the
      observed associations, and the conclusion that it has been established that HT
      increases the risk of breast cancer is not justified.

PMID- 15259278
TI  - Guidelines for the hormone treatment of women in the menopausal transition and
      beyond.

PMID- 15259279
TI  - Different cerebrovascular effects of medroxyprogesterone acetate and
      norethisterone acetate in the New Zealand White rabbit.
AB  - OBJECTIVE: The lack of a cardioprotective effect of hormone replacement therapy
      (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS)
      and Women's Health Initiative (WHI) may in part be explained by the progestin
      used. The aim of this study was to elucidate the effect of different progestins
      on cerebrovascular reactivity in an animal model. METHODS: Fifty-six
      ovariectomized New Zealand White rabbits were randomized into seven groups
      receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10
      mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens
      (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day +
      1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the
      basilar and posterior cerebral arteries were mounted in myographs for tension
      recordings. Concentration-response curves to potassium, acetylcholine, sodium
      nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and
      endothelin-1 were established. RESULTS: Treatment with MPA caused a significant
      increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p <
      0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium
      (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to
      endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when
      compared with NETA. This difference was neutralized in the groups receiving the
      combined treatment of MPA + CEE and NETA + E2. No overall differences were seen
      between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment
      causes a higher development in arterial tension compared with NETA, indicating
      that different progestins may display different cerebrovascular effects. However,
      when accompanied by estrogens, as in the case of HRT, this difference is
      eliminated.

PMID- 15259281
TI  - Comparison of the effects of two different types of calcium supplementation on
      markers of bone metabolism in a postmenopausal osteopenic population with low
      calcium intake: a double-blind placebo-controlled trial.
AB  - OBJECTIVE: To investigate calcium supplements in postmenopausal women. Calcium
      supplements in postmenopausal women with a low calcium intake have been shown to
      prevent osteoporotic vertebral fracture, but calcium is variably absorbed and
      often poorly tolerated, which may limit effectiveness. METHODS: The study
      compared the efficacy and tolerability of 500 mg/day of calcium in the form of
      ossein-hydroxyapatite (OHC) versus 500 mg/day of tricalcium phosphate (TCP) and
      placebo in the prevention of postmenopausal bone loss. This was a prospective
      randomized study enrolling 153 postmenopausal osteopenic women. Serum and urine
      markers of bone turnover were collected at 3 and 6 months. Bone density
      measurement was performed at baseline and 6 months in all participants, and at 12
      months in women taking OHC. RESULTS: At 3 and 6 months, both TCP and OHC
      decreased serum markers of bone formation significantly, compared with placebo.
      At 6 months, TCP and OHC decreased osteocalcin by 9.9% and 12.3%, respectively;
      the aminoterminal propeptide of type I procollagen (PINP) was decreased by 5.3%
      and 6.3%, respectively; bone-specific alkaline phosphatase was decreased by 4.3%
      and 6.7%, respectively, compared with baseline. The effects on bone resorption
      markers or on bone mineral density did not reach statistical significance,
      although OHC increased bone density by 0.8% at the spine at 12 months. Both forms
      of calcium were well tolerated and did not differ from placebo in terms of side
      effects. CONCLUSIONS: While both OHC and TCP were well tolerated and
      significantly reduced bone turnover markers, the effect of ossein-hydroxyapatite
      seems slightly superior to that of tricalcium phosphate.

PMID- 15259280
TI  - Endometrial safety and tolerability of triphasic sequential hormone replacement
      estradiol valerate/medroxyprogesterone acetate therapy regimen.
AB  - OBJECTIVE: Two randomized comparative multicenter studies were conducted to
      establish the endometrial safety and tolerability of a triphasic sequential
      hormone replacement estradiol valerate/medroxyprogesterone acetate (E2V/MPA)
      therapy regimen. METHODS: Study 1 was a randomized, double-blind, clinical phase
      III study in 399 postmenopausal women, following parallel-group design with two
      groups. The duration of study treatment was 12 or 13 cycles of 28 days. A double
      dummy technique was used to ensure blinding in the study. The investigational
      drugs were E2V/MPA triphasic and E2V/MPA biphasic (Diviseq and Divina,
      respectively; Orion Pharma). In study 2, a total of 341 subjects were randomly
      allocated by computer into two parallel groups receiving either E2V/MPA or
      estradiol/norethisterone acetate triphasic (E2/NETA, Trisequens; Novo Nordisk
      A/S) for 12-13 cycles. The study was an open, clinical phase III trial with a
      randomized, parallel-group design. Endometrial biopsies combined with
      transvaginal ultrasound were undertaken before and at the end of treatment during
      the progestogen phase. Bleeding patterns and symptom control were assessed
      throughout both studies. RESULTS: E2V/MPA triphasic was found to have similar
      endometrial effects and bleeding patterns to those with E2V/MPA biphasic and
      E2/NETA triphasic. Climacteric symptoms were relieved as quickly and effectively
      as with the two comparator treatments. No adverse drug reactions specific to
      E2V/MPA triphasic were observed. At the end of the study, the proportions of
      secretory samples were 67.1% for the combined E2V/MPA triphasic groups, 65.6% for
      the E2V/MPA biphasic group and 71.6% for the E2/NETA triphasic group. One case of
      hyperplasia occurred in the E2V/MPA triphasic group. Thus the incidence of
      hyperplasia for the combined groups was 0.33%. CONCLUSIONS: The triphasic E2V/MPA
      regimen was well tolerated and produced endometrial effects similar to those of
      the two comparators. Extending estrogen during the so-called treatment-free week
      with a lower dose of estradiol was effective in controlling vasomotor symptoms.

PMID- 15259282
TI  - Decision-making about hormone replacement therapy by women in England and
      Scotland.
AB  - OBJECTIVE: The aim of this study was to explore women's decision-making about the
      balance of risks and benefits of taking hormone replacement therapy (HRT) based
      on the latest evidence from the Women's Health Initiative (WHI) trial of combined
      HRT. METHODS: Women aged 50-69 years, who were eligible for the Women's
      International Study of long Duration Oestrogen after Menopause (WISDOM) trial,
      were invited to participate in one of eight focus groups. Participants were asked
      to discuss their views about taking HRT based on the latest international
      evidence. RESULTS AND CONCLUSIONS: Eighty-two women participated overall.
      Qualitative content analysis was applied to the discussion transcripts. Women
      regarded the decisions they make about taking HRT as highly personal, and, for
      women currently taking HRT, the overwhelming reason for continuation was
      perceived improvement in quality of life regardless of either the risks or the
      benefits in the longer term.

PMID- 15259283
TI  - A comparative study of breast cell proliferation during hormone replacement
      therapy: effects of tibolon and continuous combined estrogen-progestogen
      treatment.
AB  - OBJECTIVE: To use the fine-needle aspiration (FNA) biopsy technique to compare
      the effects of tibolone, conventional hormone replacement therapy (HRT) and
      placebo on breast cell proliferation in postmenopausal women. METHODS: A total of
      91 women were randomized to receive either estradiol 2 mg plus norethisterone
      acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective
      double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1
      monoclonal antibody. RESULTS: From the 83 women who completed the study, a total
      of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were
      evaluable for MIB-1 content. Women with assessable biopsies were younger, had a
      lower body mass index, and had higher levels of sex hormone binding globulin and
      insulin-like growth factor-I than women in whom the cell yield was insufficient.
      During treatment with E2/NETA, there was an increase in proliferation (percentage
      of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No
      significant changes were recorded during treatment with tibolone or placebo.
      There was a negative association between proliferation and serum levels of total
      (r(s) = -0.29, p < 0.05) and free (rs = -0.31, p < 0.03) testosterone.
      CONCLUSIONS: Tibolone seems to have little influence on breast cell
      proliferation.

PMID- 15259285
TI  - The effects of dietary supplementation with isoflavones from red clover on
      cognitive function in postmenopausal women.
AB  - OBJECTIVE: To examine the effects of dietary isoflavone supplementation with an
      extract from red clover on cognitive function in postmenopausal women. DESIGN:
      Thirty postmenopausal women aged greater than 60 years received either two
      tablets of an extract of aglycone isoflavones from red clover (each containing
      formononetin 25 mg, biochanin 2.5 mg and less than 1 mg of daidzein and
      genistein) for 6 months in a randomized, controlled clinical trial. Cognitive
      function tests were performed at baseline and at the end of isoflavone or placebo
      therapy. RESULTS: Isoflavone supplementation was associated with an apparent
      improvement in block design (a test of visual-spatial intelligence) compared to
      placebo (isoflavone +12%, placebo -3%; p = 0.03), no improvement in verbal memory
      compared to an improvement on placebo (isoflavone +1%, placebo +29%; p = 0.023)
      and a deterioration in digit recall compared to placebo (isoflavone -6%, placebo
      +12%; p = 0.029). However, these findings were not statistically significant when
      corrections were made for potential chance findings due to multiple comparisons.
      CONCLUSION: Isoflavone supplementation does not appear to have major short-term
      effects on cognitive function in postmenopausal women. However, further clinical
      trials are required to determine whether small effects or long-term effects on
      cognitive function occur during isoflavone supplementation.

PMID- 15259284
TI  - A low-dose start in hormone replacement therapy provides a beneficial bleeding
      profile and few side-effects: randomized comparison with a conventional-dose
      regimen.
AB  - OBJECTIVE: To compare bleeding control, efficacy and safety of two dose-ranging
      continuous combined hormone replacement therapy (HRT) regimens with those of a
      conventional continuous combined HRT. METHODS: An open, 2-year, multicenter study
      was conducted in 393 postmenopausal women recruited from 16 study sites. The
      women were randomized to three continuous combined HRT regimens. One group (n =
      131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of
      medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V +
      5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone
      acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was
      increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect
      of dose increase on bleeding control. RESULTS: The E2V/MPA regimens with a lower
      estrogen dose induced less bleeding and other adverse effects during the first
      six cycles than did the E2/NETA regimen. Bleeding disturbances and breast
      tenderness resulted in significantly more discontinuations in the E2/NETA group.
      After the estrogen dose increase in the E2V/MPA regimens, all groups showed
      comparable bleeding patterns and adverse effect profiles. The lower E2V dose was
      as effective as standard-dose E2 in relieving climacteric symptoms. All regimens
      provided excellent endometrial safety. No hyperplasias were reported.
      CONCLUSIONS: Continuous combined HRT should be started, and continued, with the
      lowest effective doses. An increase of the estrogen dose is recommended only if
      the initial dose is not sufficient for symptom control.

PMID- 15259286
TI  - Low-dose oral combination of 17beta-estradiol and norethisterone acetate in
      postmenopausal women decreases factor VII, fibrinogen, antithrombin and
      plasminogen activator inhibitor-1.
AB  - OBJECTIVE: Controversies still persist concerning hormone replacement therapy
      (HRT) and its effects upon blood coagulation and fibrinolysis. This study was
      carried out to evaluate possible effects of continuously administered low-dose
      17beta-estradiol (E2) and norethisterone acetate (NETA) on coagulation and
      fibrinolytic factors. METHODS: We conducted a randomized double-blind, placebo
      controlled, 1-year study in 120 healthy postmenopausal women. The three groups
      consisted of a placebo group (n = 40), a group receiving oral continuous combined
      E2 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined
      E2 1 mg and NETA 0.5 mg (n = 40). RESULTS: The two low doses of E2-NETA induced
      significantly lower plasma levels of factor VII, fibrinogen, antithrombin and
      plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatmen
      CONCLUSIONS: Low-dose E2 (1 mg) in combination with NETA resulted in favorable
      changes of factor VII activity and fibrinogen, compared with placebo. The lower
      plasma levels of PAI-1 may lead to increased fibrinolytic activity. These
      findings suggest a decreased risk of developing coronary heart disease.
      Antithrombin activity was also reduced, which may increase the risk of developing
      venous thromboembolism. The clinical significance of the lower levels of these
      factors remains to be clarified.

PMID- 15259287
TI  - Factors associated with total cholesterol levels in women around menopause
      attending menopause clinics in Italy.
AB  - OBJECTIVE: To obtain data on correlates of total cholesterol (TC) levels in women
      around menopause attending menopause clinics in Italy. METHODS: Since 1997, a
      large cross-sectional study has been conducted concerning the characteristics of
      women around the time of the menopause attending a network of first-level
      menopause out-patient clinics in Italy for general counselling about the
      menopause or treatment of menopausal symptoms. Women observed consecutively at
      the participating centers were eligible for the study. Up to March 2000, TC was
      measured in 23 018 cases, which are considered in this analysis. RESULTS: The
      adjusted mean level of TC rose with age, from 216 mg/dl in women aged < 50 years
      to 234 mg/dl in those aged > 57 years. Mean TC increased with body mass index
      (BMI, kg/m2), being 224 mg/dl in women with BMI < 24, 227 mg/dl in those with BMI
      24-26 and 228 mg/dl in those with BMI > 26. Considering menopausal status, the
      crude mean TC level was 216 mg/dl in premenopausal women, 227 mg/dl in women
      reporting a surgical menopause and 229 mg/dl in women reporting a natural
      menopause. These differences were still present when the analysis took into
      account the effect of age and other potential covariates, the adjusted values
      being 221, 225 and 227, respectively. Similar findings emerged when we considered
      the distribution of study subjects according to selected levels of TC (< 210, 210
      250, 251-290, < 290). For example, the odds ratio of TC 210-250 mg/dl and > 250
      mg/dl vs. < 210 mg/dl was, respectively, 1.8 and 2.8 in women aged > 57 years in
      comparison with women aged < 50 years. The corresponding odds ratio values for
      women with a BMI > 26 vs. < 24, and for women in spontaneous menopause vs.
      premenopause, were all 1.2 (all statistically significant). CONCLUSIONS: This
      analysis, based on a large data set, confirms the role of overweight as a
      determinant of TC in postmenopausal women, and indicates the role of the
      menopause as a determinant of TC level in women aged 50-60 years.

PMID- 15259288
TI  - Well-being at onset of hormone replacement therapy: comparison between two
      continuous combined regimens.
AB  - OBJECTIVES: To compare the effect on well-being of two continuous combined
      hormone replacement therapies (HRTs) in women starting treatment ('starters') and
      women switching from mainly sequential HRT ('switchers'). METHODS: This was a
      randomized, double-blind, 1-month trial, in which 249 postmenopausal women were
      treated with either conjugated estrogen plus medroxyprogesterone acetate (CE/MPA
      0.625 mg/5 mg) or 17beta-estradiol plus norethisterone acetate (E2/NETA 2 mg/1
      mg) continuously. Twelve items for measuring climacteric symptoms and well-being
      were reported daily on a validated symptom scale. RESULTS: Women taking CE/MPA
      reported lower scores for breast tenderness (p = 0.005), depression (p = 0.019),
      irritability (p = 0.004) and tension (p = 0.048), compared with women taking
      E2/NETA. Compared with pretreatment, both groups developed side-effects during
      the first week: breast tenderness, swelling and depression (p < 0.05). Starters,
      but also switchers, improved in sweats (p < 0.001 and p = 0.030). Compared with
      pretreatment ratings, switchers reported higher scores for breast tenderness (p <
      0.001), depression (p = 0.050) and negative effects on daily life (p < 0.001),
      whereas starters reported only physical side-effects (p < 0.05). A history of
      premenstrual syndrome (PMS) predicted high scores for swelling (p = 0.023),
      depression (p = 0.024), tension (p = 0.009), irritability (p = 0.027), headache
      (p < 0.001) and negative effects on daily life (p < 0.001). CONCLUSIONS: CE/MPA
      0.625 mg/5 mg is better tolerated than E2/NETA 2 mg/1 mg, and starters react
      differently from switchers. Side-effects occur more quickly than benefits with
      HRT, and are more frequent in women with previous PMS.

PMID- 15259289
TI  - Safety and efficacy of drospirenone used in a continuous combination with 17beta
      estradiol for prevention of postmenopausal osteoporosis.
AB  - OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous
      drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total
      of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year
      prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body
      as well as endometrial thickness, markers of bone turnover and serum lipids were
      measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol
      combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine,
      hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups
      versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum
      osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps
      67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol
      and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively
      (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained
      unchanged. No significant dose-related effects were found. Endometrial thickness
      increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus
      placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a
      positive effect on BMD and a potentially beneficial effect on lipids. Although
      endometrial thickness increased slightly, the safety of the endometrium was
      assured, as no cases of hyperplasia or cancer occurred.

PMID- 15259290
TI  - HT and WHI: the baby and the bathwater.

PMID- 15259291
TI  - Intravitreal taurolidine against experimental Staphylococcus epidermidis
      endophthalmitis in rabbits.
AB  - PURPOSE: Taurolidine is a broad spectrum, non-antibiotic antimicrobial agent, not
      previously tested against infectious endophthalmitis. The efficacy of
      intravitreal taurolidine in the treatment of experimental Staphylococcus
      epidermidis endophthalmitis was evaluated and compared with vancomycin in a
      rabbit model. METHODS: The right eyes of 34 albino rabbits were infected with an
      intravitreal inoculum of S. epidermidis (10(5) colony-forming units/0.1 ml). The
      right eyes of four rabbits (group 7) were not infected and served as uninfected
      controls. 24 hours after inoculation of bacteria the animals were divided into
      the following treatment groups: group 1 (7 rabbits) received intravitreal
      taurolidine at 24 hours and group 2 (7 rabbits) received at 48 hours. Group 3 (7
      rabbits) received vancomycin at 24 hours and group 4 (7 rabbits) at 48 hours.
      Group 5 (3 rabbits) received polyvinylpyrrolidone at 24 hours and group 6 (3
      rabbits) at 48 hours. Clinical scoring was performed at 24, 48 and 72 hours. At
      72 hours post inoculation, vitreous samples were collected for quantitative
      microbiological studies and then, the eyes were enucleated for histopathological
      scorings. RESULTS: The clinical and histopathological examinations revealed
      significant amelioration of inflammation in eyes treated with taurolidine and
      vancomycin when compared with polyvinylpyrrolidone. The eyes treated with
      taurolidine also had significantly lower colony forming units than the eyes
      treated with polyvinylpyrrolidone and taurolidine rendered many eyes sterile.
      CONCLUSION: Taurolidine is expected to be a potential agent for treatment of S.
      epidermidis endophthalmitis.

PMID- 15259292
TI  - Measurement procedures in confocal choroidal laser Doppler flowmetry.
AB  - PURPOSE: To estimate a practical number of measurements within a series of
      recordings with a confocal choroidal laser Doppler flowmeter, capable of
      providing an adequate statistical power for future studies. METHODS: Ten
      independent measurements of choroidal blood flow were obtained within 30 minutes
      in one randomly selected eye of 24 subjects. In 12 subjects, subsequent series of
      10 measurements were also obtained 2 and 7 days after baseline assessment.
      Average and median values of these series were calculated for the choroidal blood
      flow parameters velocity, volume, and flux, using either the first 3, the first
      4, the first 5, the first 6, the first 7, the first 8, the first 9, or all 10
      measurements. The variance between the series was analyzed using non-parametric
      tests. RESULTS: The average values of a series of independent measurements
      decreased with an increasing number of independent measurements. More than 5-7
      independent recordings did not markedly influence the estimate of the average
      value of choroidal blood flow parameter for an individual. Baseline measurements
      showed markedly higher values than subsequent series. Average values obtained
      with 6 independent measurements seem to provide a reasonable level of statistical
      power for paired comparisons, 13 subjects providing a 80% power at a probability
      level of 0.05 to find a significant difference of 15% between two means.
      CONCLUSION: It seems recommendable that experimental measurements with a confocal
      choroidal laser Doppler flowmeter are preceded by a session of familiarization
      and that average values of series of at least 6 measurements are used.

PMID- 15259293
TI  - A new paradigm for corneal wound healing research: the white leghorn chicken
      (Gallus gallus domesticus).
AB  - PURPOSE: To evaluate the chicken cornea as a model for corneal wound healing
      research. METHODS: We conducted studies on normal chicken corneas and on corneas
      following mechanical debridement and photorefractive keratectomy (PRK). RESULTS:
      The chicken cornea possesses six distinct layers that resemble the layers of the
      human cornea, including a substantial Bowman's layer measuring 5.2 +/- 0.3 microm
      thick. Reepithelialization time was 44.8 +/- 1.1 hours with a sliding rate of
      75.3 +/- 3.2 microm/hour following mechanical debridement and 54.4 +/- 2.8 hours
      with a sliding rate of 63.3 +/- 3.2 microm/hour for PRK-treated corneas.
      Biomicroscopic haze post-PRK peaked at 4-6 weeks and regressed until 20 weeks
      post-PRK. Histologic and clinical observations of wound healing strongly
      paralleled that noted in humans. CONCLUSION: The chicken cornea's morphology and
      wound healing response render it a useful model for corneal wound healing
      investigations.

PMID- 15259294
TI  - Blood-retinal barrier breakdown induced by activation of protein kinase C via
      vascular endothelial growth factor in streptozotocin-induced diabetic rats.
AB  - PURPOSE: To investigate (1) the mechanism of blood-retinal barrier breakdown
      induced by protein kinase C (PKC) activation (2) the relationship between PKC
      activation and vascular endothelial growth factor (VEGF) in 2-week streptozotocin
      induced diabetes. METHODS: Retinal PKC activities, retinal and vitreous
      concentration of VEGF protein were conducted by enzyme-linked immunoabsorbent
      assay (ELISA). Retinal VEGF mRNA expression was analyzed by semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR). Blood-retinal barrier
      breakdown was quantified using the Evans blue technique. Alteration of retinal
      VEGF and blood-retinal barrier were observed after intravitreal injection of PKC
      inhibitor, GF109203X, in 2-week diabetic rats. RESULTS: Two weeks of diabetes in
      rats resulted in elevation of retinal PKC specific activities, retinal and
      vitreous VEGF, and retinal vascular permeability. Retinal VEGF and retinal
      vascular permeability were decreased after intravitreal injection of GF109203X
      (10(-5), 10(-6) mol/L) in a dose-dependent manner. CONCLUSIONS: The results from
      this study showed that enhanced expression of VEGF and PKC in early diabetes and
      the blood-retinal barrier breakdown of early diabetic retinopathy induced by PKC
      activation may be partly due to the upregulation of VEGF. PKC inhibitor could
      reverse the blood-retinal barrier breakdown.

PMID- 15259295
TI  - Neuronal gene expression and function in the growth-stimulated R28 retinal
      precursor cell line.
AB  - PURPOSE: Proliferative retinal progenitor cells that express neuronal
      characteristics are potentially useful for developmental studies and as
      experimental graft material. The continuously-growing R28 retinal cell line has
      been distributed to over 60 laboratories for a variety of studies, yet has not
      been fully characterized. In this study, we tested the hypothesis that the
      proliferative R28 retinal cell line contains subpopulations of cells that express
      neuronal mRNAs and proteins characteristic of CNS neurons. METHODS: To this end,
      we sought to determine the potential retinal, neuronal, and growth-related
      characteristics of this retinal cell line through gene expression profiling,
      coupled with confirmatory immunocytochemistry and electrophysiology. RESULTS:
      Despite expression of growth-stimulatory oncogenes and growth-promoting factors,
      subpopulations of R28 cells express abundant retinal and neuronal markers, as
      well as the functional capacity to respond to specific neurotransmitters such as
      dopamine, acetylcholine, serotonin, and glycine. CONCLUSION: Proliferative R28
      cells retain functional neuronal properties that may prove useful in future
      studies of neuronal differentiation and development.

PMID- 15259296
TI  - Controlled-release oxycodone is better tolerated than intravenous
      tramadol/metamizol for postoperative analgesia after retinal-surgery.
AB  - PURPOSE: We assessed the clinical efficacy and tolerance of controlled-release
      oxycodone (CRO), comparing it with intravenous tramadol/metamizol combination in
      this prospective, randomised, double-blind study of 35 ASA physical status I-III
      patients undergoing retinal-surgery. METHODS: General anaesthesia using
      remifentanil and propofol was performed for surgery. On arrival in the recovery
      room patients were randomly allocated to two groups. The controlled-release
      oxycodone group (CRO Group) received 10 mg CRO. 12 h after the initial dose
      another 10 mg CRO were administered. Simultaneously with the initial CRO dose,
      and every 4 h up to 24 h postoperatively, the CRO Group received intravenous
      isotonic saline infusion. On arrival in the recovery room the tramadol/metamizol
      group (TM Group) received a placebo tablet, and 12 h later a second placebo.
      Simultaneously 100 mg tramadol combined with 1 g metamizol were administered
      intravenously every 4 h until 24 h postoperatively. All patients had access to
      intravenous opioid rescue medication. RESULTS: The AUC for quality of analgesia
      was significantly higher in the CRO Group than in the TM Group (p = 0.0023).
      Patient rated quality of analgesia significantly higher in the CRO Group than in
      the TM Group 8 h (p = 0.048), 16 h (p = 0.009) and 24 h (p = 0.001)
      postoperatively. There was no statistical difference in AUC for pain scores
      between groups (p = 0.205). The CRO Group experienced significantly less nausea
      than the TM Group (p = 0.012). Six patients in the TM Group in contrast to none
      in the CRO Group interrupted the study before finishing the study protocol (p =
      0.022). CONCLUSIONS: We conclude that CRO administered twice in the first 24 h
      postoperatively is superior to intravenous tramadol/metamizol for postoperative
      analgesia after retinal surgery, with fewer adverse events and greater patient
      satisfaction.

PMID- 15259298
TI  - Are routine preoperative medical tests needed with cataract surgery? Study of
      visual acuity outcome.
AB  - PURPOSE: The aim of this prospective randomized clinical trial was to investigate
      whether routine medical testing before cataract surgery reduced the rate of
      ocular surgical complications and to study its impact on visual acuity outcome.
      METHODS: The study was carried out in an academic medical center in Brazil, at
      State University of Campinas, between 10 February 2000 and 10 January 2001. The
      scheduled cataract operations were randomly assigned to one of two groups: 1) to
      be preceded by routine medical testing (the "routine-testing group") or 2) not to
      be preceded by routine medical testing (the "selective-testing group"). If the
      patient was assigned to the selective-testing group, it was requested that no
      preoperative testing be performed unless the patient presented with a new or
      worsening medical problem that would warrant medical evaluation with testing. In
      the case of patients assigned to the routine-testing group, three tests were
      requested: a 12-lead electrocardiogram, a complete blood count, and measurements
      of serum glucose. Ocular surgical complications, preoperative and postoperative
      best-corrected visual acuity were recorded on a standardized form. RESULTS: The
      sample of 1025 patients scheduled to undergo cataract surgery was comprised of
      512 assigned to the routine-testing group and of 513 assigned to the selective
      testing group. The two groups had similar proportions of operations canceled and
      not subsequently rescheduled, 2% in each group. The cumulative rate of ocular
      surgical complications was similar in the two groups, 20.5% in the routine
      testing group and 19.3% in the selective-testing group (p = 0.624). The
      preoperative and the postoperative best-corrected visual acuity were similar in
      both groups (p = 0.999 in the former and p = 0.664 in the latter). CONCLUSIONS:
      The results of this study suggest that routine medical testing before cataract
      surgery did not reduce the rate of ocular surgical complications and did not
      influence visual acuity outcome.

PMID- 15259297
TI  - Chloroquine causes lysosomal dysfunction in neural retina and RPE: implications
      for retinopathy.
AB  - Chronic use of chloroquine has been shown to induce numerous pathophysiological
      defects in the retina. This drug has the ability to alter pH of intracellular
      compartments and lysosomal function of the retinal pigment epithelium (RPE) and
      retinal neurons may constitute the basis of chloroquine retinopathy. The aim of
      the current study was to investigate pathogenic alterations in retinal cells
      continuously exposed to chloroquine using appropriate in vivo and in vitro
      models. Male hooded Lister rats were implanted with osmotic mini pumps which
      released chloroquine continuously over a period of seven days. The eyes were
      processed for electron microscopy and ultrastructural abnormalities determined in
      the neural retina and quantified using stereology in the retinal pigment
      epithelium (RPE). RPE were also exposed to chloroquine in vitro and lysosomal pH
      changes were investigated using a pH sensitive probe. Degradative capacity was
      also analysed using FITC labeled rod outer segments (ROS). Chloroquine-treated
      animals displayed several ultrastructural abnormalities including numerous
      membranous cytoplasmic bodies (MCBs) in retinal neurons. Cone photoreceptors
      displayed numerous MCBs although rods did not. The RPE of the treated groups all
      showed significantly higher numbers of lysosomal associated organelles (LAO) than
      the control group (p < 0.001). The in vitro experiments demonstrated chloroquine
      mediated rises in lysosomal pH and an increase in lysosome/phagosome accumulation
      of ROS in the chloroquine treated group (p < 0.01). The current study
      demonstrates that chloroquine disrupts lysosomal function in retinal neurons and
      RPE. The evidence presented provides a clear pathogenic basis for the functional
      defects experienced by patients with chloroquine retinopathy.

PMID- 15259299
TI  - Efficacy of verteporfin photodynamic therapy on laser-induced choroidal
      neovascularization and the ancillary effect on diabetic microvasculopathy.
AB  - PURPOSE: To demonstrate the efficacy of photodynamic therapy (PDT) in treating
      choroidal neovascularization (CNV) induced by laser photocoagulation for diabetic
      macular edema and its ancillary effect on surrounding diabetic microvascular
      abnormalities. METHODS: A retrospective interventional case series study in a
      clinical practice setting of four patients with proliferative diabetic
      retinopathy and clinically significant macular edema who had developed classic
      CNV in proximity to the area of previous laser photocoagulation. The lesions were
      treated with verteporfin PDT and followed with serial fluorescein angiography.
      RESULTS: Compared to the pre-treatment angiogram, an acute reduction in leakage
      from CNV was noted as soon as 5 days post-PDT and persisted in some areas up to
      three months post-treatment within the zone of the typical dark choroid pattern.
      No evidence of any closure of microaneurysms was noted. CONCLUSIONS: Serial
      fluorescein angiograms demonstrate that PDT appears to have a beneficial effect
      on CNV induced by laser photocoagulation for diabetic macular edema without any
      tangible beneficial effect on diabetic microvasculopathy. PDT had no effect on
      existing microaneurysms.

PMID- 15259300
TI  - [Type 1 and type 2 diabetes: clinical parallels].

PMID- 15259301
TI  - [Type 1 and type 2 diabetes: molecular parallels].

PMID- 15259302
TI  - [Type 2 diabetes and B cell deficit].

PMID- 15259303
TI  - [Adipose tissue cytokines and insulin resistance].

PMID- 15259304
TI  - [2004 Apollinaire Bouchardat prize. Muscle gene expression regulation by insulin.
      Abnormalities in type 2 diabetes].

PMID- 15259305
TI  - [Why and how to evaluate physical activity?].

PMID- 15259306
TI  - [Physical activity in the adolescent: reality or challenge?].

PMID- 15259307
TI  - [Metabolic effects of physical activity in the type 2 diabetic].

PMID- 15259308
TI  - [Type 2 diabetes: what exercise for which diabetic and how to prescribe?].

PMID- 15259309
TI  - [Glucagon 2004: homage to Roger Assan].

PMID- 15259310
TI  - [GIP and GLP-1: multiplicity of regulator mechanisms for insulin secretion].

PMID- 15259311
TI  - [GLP-2 peptide(glucagon-like peptide-2) controls energetic homeostasis by actions
      on proliferation and cytoprotection in the gastrointestinal epithelium].

PMID- 15259312
TI  - [Miniglucagon: is the precursor a traitor to its family or a genius? ].

PMID- 15259313
TI  - [Should hormone replacement therapy for menopause be continued in diabetic
      women?].

PMID- 15259314
TI  - [Allergy to insulin in 2003].

PMID- 15259316
TI  - [Psychosomatic approach].

PMID- 15259315
TI  - [Driving accidents and diabetes: risks and prevention].

PMID- 15259317
TI  - [Tension parameters, cardiovascular risk, objective and beneficial therapeutics
      in arterial hypertension].

PMID- 15259318
TI  - [Arterial remodeling on diabetes].

PMID- 15259319
TI  - [Arterial pressure: normal values, measurement techniques, treatment and
      objective thresholds].

PMID- 15259320
TI  - [Arterial hypertension during diabetes, choice of antihypertensive treatment].

PMID- 15259321
TI  - [Maurice Derot Prize 2004. Should C-peptide be put in the insulin bottle?].

PMID- 15259322
TI  - Lichtheim's "house".

PMID- 15259323
TI  - A revised method for analysing neglect using the landmark task.
AB  - In order to better disentangle 'perceptual' and 'response' biases in neglect
      patients, Bisiach and his co-workers developed a new version of the 'landmark
      task'. In their version, subjects are required to choose which is the longer
      (first condition) or the shorter (second condition) of the two portions of a pre
      bisected horizontal line. Two indices were proposed, for the purpose of measuring
      perceptual and response bias respectively. The perceptual bias index (PB) is the
      constant error across conditions, while the response bias index (RB) is the
      degree of response consistency between conditions. Although valuable in a
      clinical context, these indices are not mathematically independent of one
      another. Furthermore, they do not exploit all of the information available in a
      given set of landmark data, since the responses made at the different landmark
      locations are all averaged together. To overcome these problems, we propose two
      new indices that can be derived from the revised landmark task. Our perceptual
      bias index is the Point of Subjective Equality (PSE)--the mean landmark location
      that appears to be halfway along the line. The response bias index, M, is the
      mean probability of making a response that opposes the patient's subjective
      midpoint. PSE and M are mathematically independent of each other and use most of
      the landmark information. The method and its theoretical foundation are
      summarized, and illustrative data obtained from brain damaged patients and
      control subjects are presented. Finally, computational procedures are provided
      for both PSE and M.

PMID- 15259324
TI  - Spatiotemporal dynamics of attention in visual neglect: a case study.
AB  - Patients with visual neglect are often unaware of contralesional visual stimuli.
      Recent studies have demonstrated non-spatial as well as spatial deficits in
      allocating attention in neglect patients. We examined the spatiotemporal dynamics
      of directing attention in a patient with neglect for visual objects appearing in
      the left side of space by using a version of the attentional blink paradigm.
      presenting two visual stimuli in succession. The first target (T1) was presented
      at fixation. The location of the second target (T2) and time between the two
      targets was varied. When T2 appeared to the left, the patient required more time
      between targets to identify both accurately, compared to when T2 appeared at
      fixation or to the right. Our findings demonstrate a spatial and temporal
      gradient of attention. The results are discussed with respect to current models
      of visual processing in visual neglect.

PMID- 15259325
TI  - The use of optokinetic stimulation in rehabilitation of the hemineglect disorder.
AB  - The aim of this study was to investigate whether it is possible to strengthen the
      rehabilitation of spatial hemineglect by combining standard training for spatial
      scanning with optokinetic stimulation. A simple randomized design was used: one
      group of neglect patients was treated with a combination of the two techniques,
      and a second group received only the standard treatment. Both treatments were
      given for six consecutive weeks and produced significant improvements. However,
      addition of the optokinetic stimulation did not improve the patients'
      performance. Also, none of the independent variables (i.e., presence/absence of
      hemianopia) predicted the positive effect occasionally observed in individual
      patients.

PMID- 15259326
TI  - Biographical knowledge: modality-specific or modality-neutral?
AB  - A number of patients have been reported who produce more semantic information in
      response to faces than to names, and vice versa (e.g., Eslinger et al., 1996). It
      has sometimes been claimed that these patterns are consistent with the hypothesis
      that faces and names gain access to separate, modality-specific, biographic
      knowledge systems. Resolving this debate has proved somewhat difficult, however,
      given limitations of existing data. Not only are there relatively few patients
      showing these particular patterns of differentiation, but also testing has often
      not been sufficiently thorough to rule out alternative accounts. In this paper,
      we present results of two studies investigating biographical knowledge
      differences in neurological patients and healthy adult controls. The first study
      focused on two patients who appeared to access more information about famous
      people in response to their names than to their faces. On superficial analysis,
      this pattern could be seen to support the notion of modality-specific
      biographical knowledge systems. However, closer examination revealed that, for
      both cases, the findings could be explained by a difficulty in face recognition,
      rather than by assuming separate semantic representations for faces and names.
      The second study investigated the role of face and name cues in accessing
      biographical information in younger and older healthy adults. We found that
      accuracy in retrieval of biographical information was significantly better with
      name cues for both groups. Results from these studies not only highlight the
      processes that must be examined in order to demonstrate modality-specific
      differences conclusively, but also reveal a fundamental bias in retrieval of
      biographical knowledge that has not been addressed in research of this nature.

PMID- 15259327
TI  - Evidence for a new conceptualization of semantic representation in the left and
      right cerebral hemispheres.
AB  - Two experiments are reported that examined qualitative differences in how
      semantic information is represented in the two hemispheres. In the first
      experiment, items that were associatively related but did not share semantic
      features or membership in semantic categories produced priming when delivered to
      the LH (RVF) but not to the RH (LVF). In the second experiment items that shared
      semantic features but were neither associates nor in the same category produced
      priming in the RH (LVF), but not in the LH (RVF). Together, the two experiments
      support the theory that, in the right hemisphere, semantic memories are
      represented within a distributed system, on the basis of semantic features,
      whereas, in the left hemisphere representations are, as in local models,
      relatively more holistic, and are connected via associative links.

PMID- 15259328
TI  - Metaphor comprehension in right brain-damaged patients with visuo-verbal and
      verbal material: a dissociation (re)considered.
AB  - Metaphor comprehension was investigated in 50 right-hemisphere damaged (RHD)
      patients and 38 control subjects in two experimental conditions: a visuo-verbal
      and a verbal test. In the visuo-verbal test, subjects had to match a metaphorical
      sentence with one of four pictures representing the correct metaphorical meaning,
      the literal meaning, a control metaphor and a control literal meaning. In the
      verbal test, a metaphorical sentence had to be matched to a correct written
      metaphorical interpretation, a literal or a control interpretation. On both
      tests, the number of correct metaphorical responses in the RHD group was lower
      than in the control group. However, RHD patients performed more poorly in the
      visuo-verbal than in the verbal condition. Interestingly, when they selected the
      wrong response, the RHD patients tended to select the literal one only in the
      visuo-verbal condition. Context does not seem to be responsible for the
      dissociation between the two tests. The influence of the RHD patients' major
      visuo-spatial deficits was also checked, to exclude their role in the tendency to
      be literal with visuo-verbal material. Results are discussed in the perspective
      of an integration deficit.

PMID- 15259329
TI  - A new standardized set of ecological pictures for experimental and clinical
      research on visual object processing.
AB  - A new set of 174 pictures in black-and-white, coloured and spatially filtered
      versions, taken from photographs of real objects belonging to different semantic
      categories, was realised for experimental and clinical research on visual object
      processing. Two samples, one of English speakers and one of Italian speakers,
      were tested in order to provide the normative data for each picture, in both
      black-and-white and coloured versions, in relation to familiarity, visual
      complexity and name agreement.

PMID- 15259330
TI  - Left on the right or viceversa: a case of "alternating" constructional
      allochiria.
AB  - We describe a patient with an ischemic right frontal lesion and mild left neglect
      who showed a systematic tendency to transpose drawings on one side of the page,
      which varied depending on the starting point (left or right) of his graphic
      productions. When not specifically cued, the patient started to draw in the
      ipsilesional (right) side and tended to show allochiria on the right, but
      occasionally, or under specific instructions, the patient started drawing from
      the left side and then showed a complete reversion of his spatial transpositions.
      To clarify the basic mechanisms underlying such a peculiar constructional
      phenomenon, we performed a series of experimental investigations, including
      extended copying tasks, a clock-marking test (to mark the position of single
      hours on a clock-face), and a line bisection task with progressive left-toright
      or right-to-left stimulus presentation. Findings suggested that "alternating"
      allochiria in copying and drawing from memory tasks is an epiphenomenon of a
      basic inability to move attention and action away from the starting point of
      graphic productions. The present case study, contrasted with observations on
      other brain-damaged patients, demonstrates that allochiria may have different
      neuro-cognitive bases and offers new insights for theoretical interpretations of
      unilateral spatial neglect.

PMID- 15259331
TI  - Malingering and retrograde amnesia: the historic case of the Collegno amnesic.
AB  - Assessment of feigned cognitive disorders is an important field of
      neuropsychology because of its applications to forensic settings. Strategies for
      detecting malingering in amnesia are available for anterograde amnesia. Less
      attention has been given to malingering in retrograde amnesia. The case of the
      'Smemorato di Collegno' (The Collegno Amnesic) is probably the most famous case
      of malingered retrograde amnesia ever known in Italy. In 1926, a man who appeared
      to have lost all his autobiographical memories and identity spent nearly a year
      in the Collegno asylum of Turin without a name. He was later initially identified
      as Giulio Canella, Director of the 'Scuola Normale di Verona' who had disappeared
      during the war in 1916. He was suspected of later identified as being Mario
      Bruneri, a petty crook from Turin who played the part of an amnesic whose
      retrograde memory gradually returned. A lengthy investigation was required before
      this conclusion was reached. Several clinicians and renowned academics evaluated
      the case, but only Alfredo Coppola, diagnosed "malingered retrograde amnesia"
      using a method that was extremely innovative for the times. The aim of the
      present paper is to review the original cognitive evaluation and the strategies
      used for malingering detection in the "Collegno case". The outcome of the case is
      then discussed in the light of present-day forensic neuropsychology and the level
      of advancement of mental examination achieved in the 1920s in Europe is
      highlighted.

PMID- 15259332
TI  - Statistical methods for single-case studies in neuropsychology: comparing the
      slope of a patient's regression line with those of a control sample.
AB  - Performance on some neuropsychological tests is best expressed as the slope of a
      regression line. Examples include the quantification of performance on tests
      designed to assess the accuracy of time estimation or distance estimation. The
      present paper presents methods for comparing a patient's performance with a
      control or normative sample when performance is expressed as slope. The methods
      test if there is a significant difference between a patient's slope and those
      obtained from controls, yield an estimate of the abnormality of the patient's
      slope, and provide confidence limits on the level of abnormality. The methods can
      be used with control samples of any size and will therefore be of particular
      relevance to single-case researchers. A method for comparing the difference
      between a patient's scores on two measures with the differences observed in
      controls is also described (one or both measures can be slopes). The methods
      require only summary statistics (rather than the raw data from the normative or
      control sample); it is hoped that this feature will encourage the development of
      norms for tasks that use slopes to quantify performance. Worked examples of the
      statistical methods are provided using neuropsychological data and a computer
      program (for PCs) that implements the methods is described and made available.

PMID- 15259333
TI  - Cortex, countercurrent context, and dimensional integration of lifetime memory.
AB  - The correlation between relative neocortex size and longevity in mammals
      encourages a search for a cortical function specifically related to the life
      span. A candidate in the domain of permanent and cumulative memory storage is
      proposed and explored in relation to basic aspects of cortical organization. The
      pattern of cortico-cortical connectivity between functionally specialized areas
      and the laminar organization of that connectivity converges on a globally
      coherent representational space in which contextual embedding of information
      emerges as an obligatory feature of cortical function. This brings a powerful
      mode of inductive knowledge within reach of mammalian adaptations. It combines
      item specificity with classificatory generality, as embodied in "latent semantic
      analysis" algorithms. Its neural implementation is proposed to depend on an
      obligatory interaction between the oppositely directed feedforward and feedback
      currents of cortical activity, in countercurrent fashion. Direct interaction of
      the two streams along their cortex-wide local interface supports a scheme of
      "contextual capture" for information storage responsible for the lifelong
      cumulative growth of a uniquely cortical form of memory termed "personal
      history." This approach to cortical function helps elucidate key features of
      cortical organization as well as cognitive aspects of mammalian life history
      strategies.

PMID- 15259334
TI  - The Calvinist cortex: penetrating evolutionary predestination. Commentary on
      "Cortex, countercurrent context, and dimensional integration of lifetime memory"
      by Bjorn Merker.

PMID- 15259335
TI  - Local versus global recurrency commentary on: Cortex, countercurrent context, and
      dimensional integration of lifetime memory by Bjorn Merker.

PMID- 15259336
TI  - Tribute to Elizabeth Bates.

PMID- 15259337
TI  - [Congenital percutaneous aortic valvuloplasty in 70 subjects with congenital
      aortic stenosis, mid-term results].
AB  - OBJECTIVE: To evaluate mid-term results with Percutaneous aortic valvuloplasty
      (PAV). MATERIAL AND METHODS: Records of 70 patients treated with percutaneous
      aortic valvuloplasty with at least 6 months follow-up were reviewed. RESULTS: The
      70 patients with PAV aged 3 months to 36 years, mean 10.5 +/- 10.6 years, 40)
      63%) were male and 26 (37%) female. Initial systolic peak gradient decreased from
      84 +/-20 to 31 +/- 16 mmHg (p < 0.05), while the reduction percentage ranged from
      25 to 100%, mean 60 +/- 22. Balloon/aortic annulus index was 0.9 +/- 0.17. Ten
      (14.1 %) patients developed aortic insufficiency after PAV. Follow-up ranged from
      6 to 168 months, mean +/- 48 months. At end of follow-up, 21 patients (30%) were
      considered failed cases and 49 (70%) patients had a successful outcome.
      CONCLUSIONS: This study showed a series with the longest follow-up in Latin
      America with PAV. New prospective and multicentric studies are needed in this
      region.

PMID- 15259338
TI  - [Giant clivus chordomas. Are extensive surgeries really justified?].
AB  - Because of their location and biological behavior, clivus chordomas are tumors
      that still represent a great challenge, mainly when they have reached huge
      dimensions. In this paper we have selected the patients with the biggest clivus
      chordomas to analyze if they really can be helped with the current surgical
      procedures with the morbidity that it implies. Eleven patients with giant clivus
      chordomas were included. All of them were operated on following the recent
      criteria of Cranial Base Surgery. It was mainly analyzed, if the degree of the
      resection had any relation to the postoperative functional outcome and the
      disease-free survival time; it was also evaluated if there existed a correlation
      between the pathologic findings and the clinical course. It was possible to get a
      total resection in 8 patients and partial in 3. In all cases there was an evident
      improvement in their postoperative functional outcome, specially in those with
      complete resections. The disease-free survival time was also greater in the
      patients with more ample resections. There was not any correlation among the
      histologic variety of tumors (typical or chondroid) and the clinical prognosis.

PMID- 15259339
TI  - [Abnormal pre-surgical tests and their association with tramp-surgical
      hemorrhagic complication in elective surgery].
AB  - MAIN OBJECTIVE: To determine whether abnormal preoperative coagulation tests
      (PCT) are related to trans-surgical bleeding complication (TSBC) during elective
      surgical procedures. MATERIAL AND METHODS: Adult patients, undergone some
      elective surgical procedure in a tertiary care medical center, in Merida,
      Yucatan, Mexico in whom TSBC was looked for, were selected in a non-random
      fashion and included. TSBC was considered when bleeding in the surgical bed was >
      or =300 ml. Prothrombin time (PT) and partial thromboplastin time (PTT) were the
      PCT measured and compared against TSBC. To analyze data, inferential statistics
      was used. RESULTS: Eighty four males (49%) and 86 females (51%), were included.
      PT, PTT or both were requested to 100% of the them. PT was prolonged in 26 (15%),
      and PTT was prolonged in 14 (8%) patients. TSBC was documented in 30 patients
      (18%), although among those with and without bleeding, neither PT averages
      difference (P=0.76), nor PTT averages difference (P= 0.83), were statistically
      significant. In comparing TSBC and its relationship to abnormal PCT, again
      neither PT nor PTT were associated with bleeding (Fisher's exact tests for each:
      P= 0.41 and P= 1.0, respectively). CONCLUSION: In this sample, abnormal PCT were
      not associated with TSBC.

PMID- 15259340
TI  - [Hospital mortality at the Manuel Velasco Suarez National Institute of Neurology
      and Neurosurgery (1995-2001)].
AB  - To improve health policies directed toward ameliorating quality and also to
      characterize the profile of patients who attend medical centers, it is necessary
      to determine causes of mortality in any healthcare organization. OBJECTIVE: To
      analyze time-trend hospital mortality at the Manuel Velasco Suarez National
      Institute of Neurology and Neurosurgery (MVS-NINN) between 1995 and 2001.
      METHODS: Data were taken from database of morbidity, and mortality of MVS-NINN.
      All cases were coded by the International Classification of Disease (10th
      edition). We calculated specific rates of mortality and time-trends during a 7
      year-period. RESULTS: When main causes of mortality were included in these
      analyzes, rates of hospital mortality at MVS-NINN showed a non-significant
      tendency to decrease during this period. CONCLUSIONS: Decline of mortality time
      trend is generally in accordance with increasing life expectancy of Mexican
      population; this increase is due to progress in medical knowledge and to new
      technological and therapeutic advances, especially in the third level
      institutions such as this institute.

PMID- 15259341
TI  - [Open vs. closed abdomen in acute peritonitis. A comparative study].
AB  - INTRODUCTION: Open abdomen is a management alternative that, however, is not
      exempt from complications. We evaluated, in a comparative manner, the handling
      with open abdomen (OA) against closed abdomen (CA) in treatment of patients with
      severe peritonitis for traumatic lesion. MATERIAL AND METHODS: We carried out an
      observational, retrospective, longitudinal, and comparative study. It included
      patients managed with diagnosis severe peritonitis due to abdominal trauma
      between 1998 and 2000. They were divided into two groups, according to management
      with OA or CA. We compared age, sex, trauma type, severity of lesion, morbility
      and mortality. RESULTS: 12 patients were managed with OA, which presented longer
      hospitalization and 24 with CA who in turn presented a greater lesion severity.
      There were statistical differences in other parameters, including complications
      and mortality. However, patients managed with OA frequently presented more
      complications. DISCUSSION: OA does not improve morbility and mortality of
      patients, although they presented less severe lesions that those managed with CA.

PMID- 15259342
TI  - [Association of the HLA-DQB*0501, allele of the major histocompatibility complex
      with gastric cancer in Mexico].
AB  - Etiology of gastric cancer is related to environmental and host factors,
      Helicobacter pylori infection is the main environmental factor, but it has been
      also proposed that some major histocomnpatibility complex genes are related to
      susceptibility and resistance to develop Helicobacter pylori associated gastric
      diseases. The aim of this study was to study distribution and frequency of some
      HLA -DQ genes, among Mexican patients harboring gastric diseases. We studied 20
      subjects suffering from gastric cancer and 40 subjects harboring Helicobacter
      pylori-associated chronic gastritis. Diagnosis was confirmed by biopsy. HLA
      genotyping was performed by a polymerase chain reaction procedure. Ninety nine
      healthy individuals were also utilized for comparative purposes. Patients with
      gastric cancer displayed high frequency of HLA-DQA1*0601 (p = 0.003; OR = 20.9,
      95% CI = 2.11-506.2) and HLA-DQB1*0501 alleles, the latter when compared to
      patients with chronic gastritis (p = 0.04; OR = 3.58, 95% CI = 1.05-12.5) and to
      healthy individuals (p = 0.002; OR = 4.5, 95% CI =1.59-12.7). According to our
      results, in addition to Helicobacter pylori infection, there are immunogeneic
      markers of the HLA-DQ region, which are determinant in confering susceptibility
      for gastric cancer.

PMID- 15259343
TI  - [New tendencies in teaching medicine. Learning strategy in medicine].

PMID- 15259344
TI  - [Historical perspective of smallpox in Mexico: emergence, elimination, and risk
      of reemergence due to bioterrorism].
AB  - Smallpox has been considered a disease of historical interest. However, given the
      2001 terrorist events in the U.S. with intentional release of spores of Bacillus
      anthracis, and the current political worldwide agenda, the risk of bioterrorism
      has become a global public health concern. The risk of an intentional release of
      Variola virus as a biological weapon mandates a critical review of the historical
      impact of the disease in our country and the possible risk of its intentional
      reemergence. Smallpox was introduced into susceptible Indian populations in the
      Americas in the 16th century, contributing to the collapse of the Aztec Empire.
      Francisco Xavier Balmis start a vaccination campaign in the New World, and his
      efforts are considered the first eradication campaign of vaccine preventable
      diseases. Due to his efforts, smallpox was eliminated in Mexico in 1951. In the
      posteradication era, there is small but finite risk of intentional release of
      Variola virus. In response to this risk, Mexico has developed a comprehensive
      National preparedness plan. The impact of a new epidemic of smallpox will be
      considered a catastrophic event from both a historical and public health
      perspectives.

PMID- 15259345
TI  - [Phosphorylation of tau and Alzheimer's disease].
AB  - Tau is an important component of neuronal cytosqueleton; the protein stabilizas
      microtubules, maintains cell shape and axonal transport mechanisms. However, for
      unknown reasons tau experiments important postranslation modifications including
      enhanced phosphorilation due to unbalanced activity between kinases and
      phosphatases, affecting its normal biological function. Under these circumstances
      tau begins to aggregate into neurofibrillary tangles (NFTS) complexes which are
      pathological hallmarks of Alzheimer's disease together with senile plaques. This
      review is mainly concerned with the role that different kinase play into the
      regulation of tau structure and function.

PMID- 15259346
TI  - [Forty three-years-old woman with high blood pressure, respiratory tract
      infection, asthenia, adynamia, hyporexia, and icteric tint].

PMID- 15259347
TI  - [Giant cell glioblastoma. Case report].
AB  - Glioblastomas (World Health Organization, (WHO), grade IV) are the most frequent
      and malignant neoplasms of the human nervous system. Giant cells glioblastomas, a
      subtype of these, account for less than 1% of all brain toumors and up to 5% of
      glioblastomas. We present the case of a female who was diagnosed and treated for
      a right intra and paraventricular giant cell glioblastoma. We enfatize the
      importance of histological features of this toumor related to its prognosis.

PMID- 15259348
TI  - [Acute pancreatitis, diabetes, and sacoidosis. Case report and review of the
      literature].
AB  - INTRODUCTION: Sarcoidosis is a systemic, chronic, granulomatous disease of
      unknown cause. Pancreatic affection is rare and even more rare is the association
      among sarcoidosis, acute pancreatitis and diabetes mellitus. This is the first
      case reported in Mexico. CASE REPORT: Male 29 years. Sarcoidosis is diagnosed
      from the patient age of 20 years, with intermittent episodes affecting
      articulate, ophthalmic, cutaneous, lung and central nervous system. At 22 years
      of age the patient was diagnostic with diabetes mellitus. He was admitted with
      severe acute pancreatitis, that causes him to die. DISCUSSION: Diabetes mellitus
      is due to sarcoidotic infiltration of pancreas. Acute pancreatitis has been
      related with inflammatory or secondary process to frequent presence of
      hypercalcemia in the sarcoidosis. Diagnosis is not easy. This type of
      pancreatitis responds to treatment with steroids.

PMID- 15259349
TI  - [The long way toward Mexican cardiology].
AB  - The evolution of medical thought from the precientific phase during Renaissance
      toward the beginning of scientific phase in the XVII Century is reviewed. This
      phase was dominated by the great event of the discovery of blood circulation. The
      irradiation of this doctrine was parallel to that of Copernican theory. Harvey,
      the starter of experimental method in medicine, graduated at the University of
      Padua, where previously studied Copernicus. There he was influenced by Galileo's
      teaching, from whom adopted the quantitative focussing for his physiological
      research. His monograph Exercitatio anatomica de motu cordis... was present in
      Mexico, although it is not possible to establish when it arrived here. Only in
      the physiological treatise of doctor Marcos Joseph Salgado (1727) the blood
      circulation is described following Harvey's doctrine. Studies in the
      cardiovascular field began here during French intervention at the same time of
      the development of our Academy of Medicine. The first observations, concerning
      the blood vessels, were of surgical interest. Between 1870 and 1900, around 30
      thesis related to cardiovascular system were presented at Mexican Medical School
      and various books related to this field were published. At the end of XIX century
      and in the beginning of the XX, some cardiovascular pharmacological
      investigations were done at the National Medical Institute under the direction of
      Dr. Fernando Altamirano. However only toward the middle of XX century it was
      possible to create and sistematize a cardiological specialty, thanks to the
      foresight of Dr. Ignacio Chavez. Cardiology today constitutes a mother discipline
      fragmented in a great number of subspecialities, each one having own
      characteristics, methodology and focussing.

PMID- 15259350
TI  - [Diaphragmatic eventration case report].

PMID- 15259351
TI  - [A new susceptibility locus for asthma].

PMID- 15259352
TI  - [The general physician, essential actor in the medicine of the future].

PMID- 15259353
TI  - [Questions to illustrate the role of philanthropy in healthcare services
      planning].

PMID- 15259355
TI  - Transmural distribution of iron in the hypoxic and reoxygenated rabbit left
      ventricular myocardium.
AB  - Transmural distribution of low molecular weight iron (LMWI), total iron, and
      protein carbonyls (PC) was investigated in the perfused rabbit heart under
      aerobic conditions, and after 60 min hypoxia followed or not by 3 min
      reoxygenation. In the aerobic perfused hearts, LMWI, total iron and PC did not
      show significant transmural differences. Hypoxia increased LMWI and PC levels,
      which were significantly higher in the subendocardium than in the subepicardium;
      further significant changes were not observed after reoxygenation. Total iron
      showed no transmural difference and was not significantly affected by both
      hypoxia and reoxygenation. Free iron was undetectable in the myocardial effluent
      of all experimental groups. Thus, hypoxia favors myocardial iron
      decompartmentalisation and oxidative stress, which are significantly greater in
      the inner than in the outer ventricular layers. Such findings may add further
      insight into the problem of the vulnerability of the mammalian subendocardium to
      injury induced by oxygen deprivation.

PMID- 15259356
TI  - Protective effect of metallothioneins against oxidative stress evaluated on wild
      type and MT-null cell lines by means of flow cytometry.
AB  - It is generally accepted that metallothioneins (MTs) are devoted to the
      regulation of the metabolism of essential trace metals and to chelation of toxic
      metals. Nowadays, there is increasing evidence that MTs also act as free radical
      scavengers. We employed wild type mouse embryo fibroblast cell line, GKA1, and
      its MT-null variant, GKA2, in order to correlate the presence of MTs to the
      sensitivity of cells to reactive oxygen species (ROS), spontaneously generated by
      the aerobic cellular metabolism, or chemically induced by hydrogen peroxide. The
      absence of MTs in GKA2 cells was unambiguously correlated to higher sensitivity
      to ROS attack, as evaluated by detection and quantification of 8-oxo-2'
      deoxyguanosine (8-oxo-G), the first product of oxidative attack to DNA, using
      Fluorescence-Activated Cell Sorter (FACS). When compared to MT-null cell line,
      the wild type cells (GKA1) were less sensitive to ROS attack. In GKA1 cells, MT
      biosynthesis is readily induced by Cd2+ treatment, and such an induction caused a
      further decrease in sensitivity to ROS injury. On the contrary, the MT-null cells
      (GKA2) expressed no detectable metallothioneins either constitutively, or after
      heavy metal pretreatment. Indeed, in GKA2 cell line, pretreatment with Cd2+ did
      not reduce but even enhanced the oxidative stress.

PMID- 15259357
TI  - The oxidative DNA base damage in testes of rats after intraperitoneal cadmium
      injection.
AB  - Cadmium is known to be a carcinogenic metal that especially its compounds have
      sufficient evidence in both humans and experimental animals beneath its
      environmental effects. Testis tissue is highly sensitive to the effects of
      cadmium. It is proposed that cadmium also increases oxygen derived free radicals
      and lipid peroxidation. As indicators of oxidative DNA damage, 6 oxidative DNA
      bases were determined by using Gas Chromatography/Mass Spectrometry-Selected Ion
      Monitoring technique. 45 Sprague-Dawley rats (225-300 g) were used as
      experimental animals and were divided into 3 groups of 15 rats. A single 2 mg
      NaCl/kg body wt, 0,5 and 1,25 mg CdCl2/kg body wt were injected intraperitoneally
      to control, low and high dose groups, respectively. 5-OH Cytosine, 8-OH Adenine
      and Fapy Guanine lesions were elevated significantly in high dose group in the
      first day. A clear dose-response relationship was seen between dose groups and 8
      OH Adenine levels related with time in all periods. There was a significant dose
      response relationship in 2-OH Adenine, Fapy Guanine and 8-OH Guanine, especially
      in the second week suggesting the inhibition of XPA protein by cadmium after
      first week. In contrast, the observation of a significant decrease of 5-OH
      Cytosine levels after first week showed that cadmium could not affect the enzymes
      repairing the cytosine base lesions.

PMID- 15259358
TI  - Copper-induced oxidative stress and antioxidant defence in Arabidopsis thaliana.
AB  - Content of reactive oxygen species (ROS): O2*-, H2O2 and OH* as well as
      activities of antioxidant enzymes: superoxide dismutase (SOD), guaiacol
      peroxidase (POX) and catalase (CAT) were studied in leaves of Arabidopsis
      thaliana ecotype Columbia, treated with Cu excess (0, 5, 25, 30, 50, 75, 100, 150
      and 300 microM). After 7 days of Cu action ROS content and the activity of SOD
      and POX increased, while CAT activity decreased in comparison with control.
      Activities of SOD, POX and CAT were correlated both with Cu concentration (0-75
      microM) in the growth medium and with OH* content in leaves. Close correlation
      was also found between OH* content and Cu concentration. Oxidative stress in A.
      thaliana under Cu treatment expressed in elevated content of O2*-, H2O2 and OH*
      in leaves. To overcome it very active the dismutase- and peroxidase-related (and
      not catalase-related, as in other plants) ROS scavenging system operated in A.
      thaliana. Visual symptoms of phytotoxicity: chlorosis, necrosis and violet
      colouring of leaves as well as a reduction of shoot biomass occurred in plants.

PMID- 15259359
TI  - Interactions between toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co,
      Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements in the tissues of cattle from NW Spain.
AB  - Since the toxicity of one metal or metalloid can be dramatically modulated by the
      interaction with other toxic or essential metals, studies addressing the chemical
      interactions between trace elements are increasingly important. In this study
      correlations between the main toxic (As, Cd, Hg and Pb) and nutritional essential
      (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements were evaluated in the tissues
      (liver, kidney and muscle) of 120 cattle from NW Spain, using Spearman rank
      correlation analysis based on analytical data obtained by ICP-AES. Although
      accumulation of toxic elements in cattle in this study is very low and trace
      essential metals are generally within the adequate ranges, there were significant
      associations between toxic and essential metals. Cd was positively correlated
      with most of the essential metals in the kidney, and with Ca, Co and Zn in the
      liver. Pb was significantly correlated with Co and Cu in the liver. A large
      number of significant associations between essential metals were found in the
      different tissues, these correlations being very strong between Ca, Cu, Fe, Mn,
      Mo and Zn in the kidney. Co was moderately correlated with most of the essential
      metals in the liver. In general, interactions between trace elements in this
      study were similar to those found in polluted areas or in experimental studies in
      animals receiving diets containing high levels of toxic metals or inadequate
      levels of nutritional essential elements. These interactions probably indicate
      that mineral balance in the body is regulated by important homeostatic mechanisms
      in which toxic elements compete with the essential metals, even at low levels of
      metal exposure. The knowledge of these correlations may be essential to
      understand the kinetic interactions of metals and their implications in the trace
      metal metabolism.

PMID- 15259360
TI  - Acidity of exogenous metal ion in the activation of calcineurin.
AB  - The pH dependent activation of calcineurin by exogenous metal ion was studied
      over the pH range from 6.5 to 9.0 in increments of 0.5 pH units. Calcineurin
      activated by Co2+, Ni2+, or Mg2+ was characterized and compared to the pH
      dependency of the Mn(2+)-activated enzyme (Martin, B.L., and Graves, D.J. (1986)
      J. Biol. Chem. 261, 14545-14550). The pH dependency of the kinetic parameters
      varied with metal ion and subsequent analysis yielded estimates for the pKa
      values for the enzyme-metal ion and the enzyme-metal ion-substrate complexes with
      each of the exogenous metal ions characterized. The evaluated pK(a)s for enzyme
      metal ion (EM) complexes showed an inverse relationship with the pK(a)s of the
      M(2+)-H2O complex. In contrast, variation of the pK(a)s for the enzyme-metal ion
      substrate (EMS) complexes showed no trend. These data support the hypothesis that
      exogenous metal ion functions to facilitate a proton transfer before the turnover
      of substrate with the acidity of the exogenous metal ion as a primary determinant
      of its participation.

PMID- 15259361
TI  - The stereoisomers of pyochelin, a siderophore of Pseudomonas aeruginosa.
AB  - The Pseudomonas aeruginosa siderophore pyochelin is obtained from the bacterial
      culture medium as a mixture of two epimers. Chromatically isolated pure
      stereoisomers equilibrate readily in most solvents. Experiments will be reported
      which allow to isolate one of the isomers in pure form and which shed some
      additional light on the epimerization reaction.

PMID- 15259362
TI  - Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the
      yeast Candida albicans to amphotericin B and miconazole.
AB  - Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory
      concentration) levels of Cu(ClO4)2 6H2O and [Cu(phendio)3](ClO4)2 4H2O (phendio =
      1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and
      amphotericin B required to achieve the MIC90 whereas pre-growth in AgClO4 and
      [Ag(phendio)2]ClO4 resulted in a small decrease in the relevant MIC90 values. The
      copper complexes reduce the oxygen consumption of C. albicans while the silver
      complexes increase oxygen consumption. In addition, pre-growth of cells in the
      copper complexes resulted in a lower ergosterol content while the silver
      complexes induced an elevation in ergosterol synthesis. The ability of copper and
      silver complexes to alter the susceptibility of C. albicans to miconazole and
      amphotericin B may be influenced by their action on respiration, since reduced
      respiration rates correlate with reduced cellular ergosterol which is the target
      for amphotericin B. Lower levels of ergosterol have previously been associated
      with elevated tolerance to this drug. In the case of reduced sensitivity to
      miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise
      to fewer toxic side products once biosynthesis is inhibited by miconazole.

PMID- 15259363
TI  - Lanthanide ions promote the hydrolysis of 2,3-bisphosphoglycerate.
AB  - The 31P NMR studies showed that lanthanide ions promote the site-specific
      hydrolysis of 2,3-Bisphosphoglycerate (BPG) at pH 7.4 by cleaving the 2'
      phosphomonoester bond. The effect of fourteen trivalent lanthanide ions and Sc3+,
      and Y3+ were compared by the percentage of hydrolysis obtained by determining the
      inorganic phosphate produced. All the trivalent lanthanide ions promote the
      hydrolysis, but Sc3+ not. Among them, Ce3+ affects the reaction mostly. This was
      mainly attributed to the autooxidation of Ce3+ to Ce4+, since the promoting
      effect of Ce3+ is related to the increasing Ce4+ amount in the solution and
      depressed by adding sulphite. Ce4+ promotes the hydrolysis more efficiently than
      Ce3+ do. The pseudo first-order rate constant for the hydrolysis of BPG by
      Ce(SO4)2 (18.7 mM) at pH 1 and pH 2, 37 degrees C is 3.1 h(-1) and 0.65 h(-1)
      respectively. A mechanism with a hydroxo species as reactive intermediate was
      proposed for the trivalent lanthanide ions. The site-specificity was explainable
      by this mechanism.

PMID- 15259364
TI  - Lack of reversal effect of EDTA treatment on cadmium induced renal dysfunction: a
      fourteen-year follow-up.
AB  - The aim of this study was to evaluate the effect of ethylenediaminetetraacetic
      acid (EDTA) on cadmium (Cd) induced renal dysfunction. Seventeen workers (14
      males, 3 females) were diagnosed with occupational Cd poisoning in 1986. These
      individuals had between 7 to 39 years of Cd exposure. From 1986 to 1999, patients
      received periodic EDTA therapy as part of their follow-up, all at the same
      hospital. Levels of urinary cadmium (UCd) and urinary beta2-microglobulin (B2M)
      were measured before and after each annual EDTA treatment period. Renal
      dysfunction was defined as urinary B2M > 0.8 mg/g Cr (creatinine). In these
      workers, patients with UCd level higher than 10 microg/g Cr in 1986 had abnormal
      B2M excretions (> or = 0.8 mg/g Cr) or trended to have abnormal B2M levels during
      the treatment period. However, in subjects with UCd concentration lower than 10
      microg/g Cr in 1986, their urinary B2M excretions either remained normal (< 0.8
      mg/g Cr) or returned to normal during the treatment period. The prevalence of
      renal dysfunction increased during the follow up period regardless of whether UCd
      levels increased or not, indicating a progressive renal dysfunction despite
      removal from Cd exposure. Our results suggest that reversibility of renal
      dysfunction caused by Cd related to the level of Cd exposure at the time of
      removal from exposure: renal dysfunction could be reversed if initial UCd < 10
      microg/g Cr, but was irreversible when UCd > 10 microg/g Cr. Repeated
      examinations on these 17 Cd exposed workers from 1986 to 1999 also revealed that
      periodic administration of EDTA had no beneficial effects on chronic Cd-induced
      renal dysfunction.

PMID- 15259365
TI  - Effects of AZT on cellular iron homeostasis.
AB  - 3'-azido-3'-deoxythymidine (AZT), the first chemotherapeutic drug approved by FDA
      for treatment of HIV-infected patients and still used in combination therapy, has
      been shown to induce, upon prolonged exposure, severe bone marrow toxicity
      manifested as anemia, neutropenia and siderosis. These toxic effects are caused
      by inhibition of heme synthesis and, as a consequence, transferrin receptor (TfR)
      number appears increased and so iron taken up by cells. Since iron overload can
      promote the frequency and severity of many infections, siderosis is viewed as a
      further burden for AIDS patients. We have previously demonstrated that AZT
      treated K562 cells showed an increase of the number of TfRs located on the
      surface of the plasma membrane without affecting their biosynthesis, but slowing
      down their endocytotic pathway. In spite of the higher number of receptors on the
      plasma-membrane of AZT-treated cells, intracellular accumulation of iron showed a
      similar level in control and in drug-exposed cells. The chelating ability of AZT
      and of its phosphorylated derivatives, both in an acellular system and in K562
      cells, was also checked. The results demonstrated that AZT and AZTMP were
      uneffective as iron chelators, while AZTTP displayed a significant capacity to
      remove iron from transferrin (Tf). Our results suggest that AZT may be not
      directly involved in the iron overloading observed upon its prolonged use in AIDS
      therapy. The iron accumulation found in these patients is instead caused by other
      unknown mechanisms that need further studies to be clarified.

PMID- 15259366
TI  - Differential effects of cadmium on blood lymphocyte subsets.
AB  - This work was designed to analyze the possible dose dependent effects of cadmium
      on the blood lymphocyte subset distribution and if these effects are related to
      circulating cadmium concentration. For that purpose, adult male rats were exposed
      for one month to 0, 5, 10, 25, 50 or 100 ppm of cadmium chloride (CdCl2) in the
      drinking water. B lymphocytes decreased in peripheral blood with the doses of 5
      and 10 ppm of CdCl2. From the dose of 25 ppm on, B cells increased. T lymphocytes
      were increased with the doses of 25, 50 and 100 ppm of CdCl2. The lower doses of
      the metal induced opposite effects. CD4+ and CD8+ cells decreased with the doses
      of 5 and 10 ppm whereas they were increased with the dose of 25 ppm of CdCl2 on.
      From the dose of 10 ppm on, cadmium concentration was increased. The results on
      the distribution of blood lymphocyte subsets suggest that cadmium inhibits the
      humoral and cellular immune response with the lower doses of the metal used, and
      opposite effects were detected with the higher doses, the effect not being
      dependent on the circulating cadmium.

PMID- 15259367
TI  - Monitoring of cobalt(II) uptake and transformation in cells of the plant
      associated soil bacterium Azospirillum brasilense using emission Mossbauer
      spectroscopy.
AB  - Interaction of cobalt(II) at micromolar concentrations with live cells of the
      plant-growth-promoting rhizobacterium Azospirillum brasilense (strain Sp245) and
      further transformations of the metal cation were monitored using 57Co emission
      Mossbauer spectroscopy (EMS). Cell suspensions of the bacterial culture (2.4 x
      10(8) cells ml(-1)) were doped with radioactive 57CoCl2 (1 mCi; final
      concentration 2 x 10(-6) M 57Co2+), kept under physiological conditions for
      various periods of time (from 2 min up to 1 hour) and then rapidly frozen in
      liquid nitrogen. Analysis of emission Mossbauer spectra of the frozen aqueous
      suspensions of the bacterial cell samples shows that the primary absorption of
      cobalt(II) at micromolar concentrations by the bacterial cells is rapid and
      virtually complete, giving at least two major forms of cobalt(II) species bound
      to the cells. Within an hour, the metal is involved in further metabolic
      transformations reflected by changes occurring in the spectra. The Mossbauer
      parameters calculated from the EMS data by statistical treatment were different
      for suspensions of live and dead (thermally killed) bacterial cells that had been
      in contact with 57Co2+ for 1 h, as well as for the cell-free culture medium
      containing the same concentration of 57Co2+. Chemical after-effects of the
      nuclear transition (57Co --> 5 7Fe), which provide additional information on the
      chemical environment of metal ions, are also considered. The data presented
      demonstrate that EMS is a valuable tool for monitoring the chemical state of
      cobalt species in biological matter providing information at the atomic level in
      the course of its uptake and/or metabolic transformations.

PMID- 15259368
TI  - Antennae: the strongest magnetic part of the migratory ant.
AB  - Pachycondyla marginata (P.m.), a migratory and termitophageous ant, hunting only
      the termite species Neocapritermes opacus, migrates significantly oriented 13
      degrees with respect to the magnetic North-South axis. Results of hysteresis
      curves at room temperature of four Pachycondyla marginata heads, thorax, pairs of
      antennae and abdomens, oriented parallel to the magnetic field, indicate that the
      antennae give the strongest saturation magnetization, suggesting this sensory
      organ as being also a magnetic sensory organ. The total saturation magnetization
      in a whole P.m. is composed by 42 +/- 3%, 24 +/- 3%, 19 +/- 3% and 15 +/- 3% of
      antennae, head, thorax and abdomen contributions, respectively. The abdomen
      hysteresis curve presents a wasp-waisted loop with Hcr/Hc of 4.75, characteristic
      of mixed magnetic systems.

PMID- 15259369
TI  - The structure of salmochelins: C-glucosylated enterobactins of Salmonella
      enterica.
AB  - Salmochelins represent novel carbohydrate containing catecholate siderophores,
      which are excreted by Salmonella enterica and uropathogenic Escherichia coli
      strains under low-iron stress. While previous analytical data showed salmochelins
      to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure
      remained elusive. Structure elucidation with electrospray ionization-Fourier
      transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D
      NMR now revealed that salmochelins are enterobactin-related compounds, which are
      beta-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key
      compound salmochelin S4 is a twofold beta-C-glucosylated enterobactin analogue.
      Comparison of partial structures of salmochelin with a C-glycosylated compound
      previously characterized by another group strongly suggest that salmochelins
      represent the long sought compounds termed Salmonella resistance factors (SRF) or
      pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12
      confers the ability to produce salmochelins. A detailed analysis proved iroB to
      be the sole gene with glycosyltransferase activity necessary for salmochelin
      production. Salmochelins compared to enterobactin are the better siderophores in
      the presence of serum albumin. This may indicate for salmochelins a considerably
      more important role for pathogenic processes in certain Escherichia coli and
      Salmonella infections than formerly assigned to enterobactin. This conclusion is
      supported by the location of the iro genes on pathogenicity islands of
      uropathogenic E. coli strains.

PMID- 15259370
TI  - Towards quality specifications in extra-analytical phases of laboratory activity.

PMID- 15259371
TI  - Quality indicators and specifications for the extra-analytical phases in clinical
      laboratory management.
AB  - BACKGROUND: Quality management systems should cover all the steps involved in the
      overall testing and non-testing processes. AIM: To identify quality indicators
      for extra-analytical processes in the clinical laboratory and to specify
      acceptability limits, in order to provide a useful tool for continuous
      improvement of laboratory service. METHODS: A literature review by Medline search
      was performed using the keywords: Q-Tracks and Q-probes alone, and management,
      error, mistake, and indicator crossed with quality, laboratory and medicine. The
      indicators retrieved were organized according to the various laboratory
      processes. Their expression was standardized in relation to the total activity of
      each process reported in each paper reviewed. The magnitude of the errors
      reported was considered to be the current state of the art for the extra
      analytical step and was proposed as the quality specification. RESULTS: Examples
      of indicators and specifications for the pre-analytical process: Analytical
      request: Error in patient identification (0.08%), request unintelligible (0.1%).
      SAMPLING: Requested but not collected (7%), redraws (2%). Transport and reception
      of samples: Inadequate transportation conditions (0.005%), hemolyzed sample
      (0.2%). Examples of indicators and specifications for the post-analytical
      process: Report validation: Test not performed (1.4%), test performed but not
      requested (1.1%). Intra-laboratory reports: Laboratory reporting errors (0.05%),
      delivery outside specified time (11%). Consulting service: average time to
      communicate critical values for inpatients (6 min). CONCLUSIONS: These extra
      analytical indicators and their specifications, expressed in a standardized
      manner, constitute a preliminary basis for comparison of individual laboratory
      performance with the purpose of improving laboratory quality.

PMID- 15259372
TI  - Pitfalls and drawbacks in screening of congenital disorders of glycosylation.
AB  - Congenital disorders of glycosylation include a group of diseases, each of them
      caused by different protein (mostly enzyme) impairment due to a specific gene
      defect. The many subtypes are classified according to clinical features,
      enzymology and molecular genetic analyses. Problems in diagnostics arise from the
      great diversity in clinical presentation, usually age-related, and different
      severities of individual types of these, by far underdiagnosed, diseases. Also
      the biochemical findings tend to vary, even within a single type. No one
      screening test, common for all types, is available so far. Several methods of
      choice may be used in the first approach; other procedures must follow for
      detailed typing of the defect. Possible drawbacks and pitfalls in the diagnostics
      from the viewpoint of our 3-year studies and practical screening experience are
      presented.

PMID- 15259373
TI  - Activity of eosinophils and immunoglobulin E concentration in the peritoneal
      fluid of women with endometriosis.
AB  - Autoinflammatory phenomena, including autoantibody production and atopy, have
      been regarded as associated with endometriosis. The present study investigates
      the activity of eosinophils and the distribution of immunoglobulin E
      concentrations in the peritoneal fluid of women with early endometriosis. The
      study group consisted of 30 patients with laparoscopically diagnosed early
      endometriosis. The healthy control group consisted of 18 females with no evident
      changes in the abdominal cavity and no endometrial foci. Concentrations of
      immunoglobulin E in serum and peritoneal blood were determined by enzyme
      immunoassay. The activity of eosinophils was estimated according to the
      expression of the early activation molecule CD69 by the flow cytometry method.
      The concentrations of immunoglobulin E in the peripheral blood and peritoneal
      fluid were similar in both groups. However, the count of CD69+ eosinophils was
      higher in the peritoneal fluid of women with endometriosis. The results indicate
      that activated eosinophils accumulate in the peritoneal fluid in early
      endometriosis and can play a significant role in the pathogenesis of the disease.

PMID- 15259374
TI  - Rapid generation of detailed loss of heterozygosity profiles for routine
      diagnosis of gliomas.
AB  - Aberrations in the genomes of gliomas seem to correlate well with clinical
      parameters. Pertinent studies, however, rely on highly sophisticated methods,
      they require large amounts of high-quality sample material and/or they demand
      profound analytical expertise. Consequently, molecular tumour analysis has not
      yet been widely implemented in routine laboratory applications. We have developed
      an easy-to-perform approach for the rapid derivation of a detailed loss-of
      heterozygosity profile from individual gliomas. DNA of PCR quality is extracted
      in a one-step procedure from routinely obtained material. A microsatellite-based
      marker set is used to detect the deletion status of genomic regions (i) with
      established diagnostic relevance, (ii) recurrently found deleted in gliomas, or
      (iii) generally associated with tumour suppressor activity. The complete profile
      comprises 25 regions and is generated from 64 markers multiplexed into 18
      reactions. Illustratively, we present findings from an anaplastic
      oligodendroglioma; the molecular data for this tumour allow refined diagnostic
      and prognostic statements that could not be derived from histology alone. Our
      approach should prove useful in the routine diagnosis of gliomas. Simultaneously,
      research data for many highly relevant regions are generated in a comparatively
      simple and inexpensive way.

PMID- 15259375
TI  - Presence of secretory group IIa and V phospholipase A2 and cytosolic group
      IValpha phospholipase A2 in chondrocytes from patients with rheumatoid arthritis.
AB  - Both secretory and cytosolic phospholipase A2 enzymes have been implicated in the
      pathogenesis of arthritis in animal models, but the exact expression patterns of
      the enzymes in diseased human joint tissue are uncertain. We investigated the
      messenger RNA expression of group IIa, IValpha and V phospholipase A2 and
      localized the presence of group IIa and IValpha phospholipase A2 at protein
      levels in articular cartilage from patients with rheumatoid arthritis,
      osteoarthritis and patients with non-arthritic joints. Both group IIa
      phospholipase A2 messenger RNA and protein were detected in all samples
      independent of diagnosis, but were far more prominent in cartilage from
      rheumatoid arthritis samples. In cartilage with rheumatoid arthritis, the enzyme
      was detected both within the chondrocytes and in the extracellular matrix,
      whereas only few osteoarthritic cartilage samples showed positive staining in the
      matrix. In the cartilage matrix of non-arthritic controls, group IIa
      phospholipase A2 was totally absent. Messenger RNA for the group IValpha and V
      phospholipase A2 was, except for one osteoarthritic cartilage sample, exclusively
      detected in rheumatoid arthritic cartilage. For group IValpha phospholipase A2
      this was also confirmed at the protein level. These results suggest that each
      phospholipase A2 enzyme has distinct roles in both healthy and diseased joint
      tissue, and that the diversity and amount of enzyme correlate with the grade of
      inflammation and disease severity.

PMID- 15259376
TI  - Neurokinin B levels in maternal circulation during early pregnancy.
AB  - Neurokinin B levels were measured between the 10th-20th weeks of pregnancy, i.e.,
      prior to the development of clinical symptoms, in women who developed
      preeclampsia or delivered a growth-restricted baby. No difference was found in
      plasma neurokinin B levels, although neurokinin B levels increased slightly
      towards term.

PMID- 15259377
TI  - Cl- regulates cryoglobulin structure: a new hypothesis for the physiopathological
      mechanism of temperature non-dependent cryoprecipitation.
AB  - Cryoglobulins are pathological cold-precipitable immunoglobulins associated with
      a number of infectious, autoimmune and neoplastic disorders. Patients, when
      exposed to low temperatures, show symptoms related to intravascular precipitation
      of such immunoglobulins. The formation of cryoaggregates induced by exposure to
      cold temperature is the key pathogenetic mechanism. The subsequent intravascular
      precipitation can account for some clinical signs of peripheral vasculitis, but
      fails to explain the precipitation of cryoglobulins in regions where no
      significant temperature changes take place. We studied, in vitro, the activity of
      different ions on temperature-dependent aggregation of cryoglobulins and found
      that the concentration of Cl- present in solution is the most important variable
      that controls the size and the rate of formation of aggregates, both at low
      temperature and at 37 degrees C. We suggest that chloride anion could be the most
      important factor involved in the pathogenesis of events in visceral regions, such
      as in the kidneys, where no temperature changes occur but where the local Cl-
      concentration changes to maintain blood electrolytic homeostasis and acid-basic
      equilibrium. Moreover, identification of a specific structural domain responsible
      for Cl- binding may provide new targets for drugs selectively designed to
      interfere with cryoglobulin aggregation.

PMID- 15259378
TI  - Urine labeling with orally applied marker substances in drug substitution
      therapy.
AB  - The compliance of 581 drug addicts attending six methadone substitution
      outpatient clinics was determined over a period of 18 months. Urine from these
      patients was labeled following oral administration of low molecular weight
      polyethylene glycols as marker substances. These substances were measured in
      approx. 5800 urine samples. A protocol for applying marker substances and ways to
      prevent substitution of urine samples were evaluated. Normal values for marker
      substances in urine were determined. The results suggest that this labeling
      procedure is a new diagnostic tool to prevent manipulation of urine samples by
      drug addicts receiving substitution therapy.

PMID- 15259379
TI  - Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in
      normal subjects and patients with heart failure.
AB  - The derangement of neuro-endocrine control of circulation influences both disease
      evolution and response to treatment in patients with heart failure, but little
      data are available about the complex relationships between the degree of neuro
      hormonal activation and clinical severity. We studied the relationships between
      cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological
      markers in a prospective cohort of 105 consecutive patients with cardiomyopathy
      (77 men and 28 women, mean age 66.7+/-12.4 years, range 33-89 years). We assayed
      the circulating levels of CNHs (atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP)), plasma renin activity (PRA), aldosterone, cortisol,
      adrenaline, noradrenaline, thyroid hormones and thyroid stimulating hormone
      (TSH), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The
      concentrations of all CNHs and neurohormones were higher in patients with heart
      failure compared to normal subjects, except for free triiodothyronine (FT3),
      which was below normal values. ANP was positively related to NYHA class, IL-6,
      adrenaline, noradrenaline and cortisol, while negatively with ejection fraction
      and FT3. BNP was positively related to age, NYHA class, IL-6, TNF-alpha,
      adrenaline, noradrenaline and cortisol, while negatively with ejection fraction
      and FT3. A stepwise multiple linear regression indicated that plasma ANP depended
      only on ejection fraction, adrenaline and noradrenaline values, while for plasma
      BNP variation NYHA class contributed too. Our data confirm a progressive
      activation of hormonal and immunological systems in patients with heart failure.
      Furthermore, CNH circulating levels in heart failure are affected not only by
      cardiac function and disease severity, but also by activation of neuro-hormonal
      and stress-related cytokine systems, as well as by the thyroid hormones, even on
      usual medical treatment.

PMID- 15259380
TI  - Clinical utility of serum holotranscobalamin as a marker of cobalamin status in
      elderly patients with neuropsychiatric symptoms.
AB  - Early diagnosis of cobalamin deficiency is crucial, owing to the latent nature of
      this disorder and the resulting possible irreversible neurological damage. A
      normal serum cobalamin concentration does not reliably rule out a functional
      cobalamin deficiency and there does not at present seem to be any single
      diagnostic approach to achieve this diagnosis. A new marker for cobalamin status
      is the serum concentration of cobalamin bound to transcobalamin II (holoTC).
      Because methods suitable for routine use have been unavailable until recently,
      the clinical value of low holoTC is still uncertain. Furthermore, there is at the
      moment no gold standard or true reference method to diagnose subtle cobalamin
      deficiency, which makes evaluation of the clinical usefulness of holoTC and the
      estimation of sensitivity and specificity problematic. In this study, we aimed to
      assess whether low holoTC concentrations are congruent with other biochemical
      signs of cobalamin deficiency in a group of psychogeriatric patients. The
      findings in the present study show that holoTC is strongly related to serum
      cobalamin (0.68; p<0.001 in both patients and controls). Distribution of the
      different markers for cobalamin/folate status in the 33 patients with low levels
      of serum holoTC (below 40 pmol/l) showed that 17 patients had normal levels of
      the other markers for cobalamin status. This may indicate poor specificity of low
      holoTC for cobalamin deficiency. In 23 out of 176 patients with normal levels of
      holoTC we observed pathological levels of other markers for cobalamin deficiency.
      The use of holoTC in the present study group did not give significant additional
      information other than that given by serum cobalamin and therefore cannot be
      recommended in this clinical setting.

PMID- 15259381
TI  - Comparison of serum creatinine, uric acid, albumin and glucose in male
      professional endurance athletes compared with healthy controls.
AB  - Owing to considerable physical, endocrinological and metabolic adaptations, the
      analysis of biochemical data in elite and top-class athletes requires caution.
      With the aim to identify metabolic and biochemical adaptations to particular
      lifestyle conditions, such as regular and strenuous physical exercise, we
      measured the concentration of serum albumin, creatinine, uric acid and glucose in
      80 male professional cyclists, 37 male members of the Italian national cross
      country ski team and 60 male healthy sedentary controls at rest. At variance with
      earlier investigations, endurance athletes showed significantly decreased
      concentrations of serum creatinine (controls: 83.1+/-11.0 micromol/l; skiers:
      78.0+/-8.4 micromol/l; p<0.05; cyclists: 73.8+/-10.4 micromol/l; p<0.01), uric
      acid (controls: 362+/-69 micromol/l; skiers: 331 +/-70 micromol/l; p<0.05;
      cyclists: 312+/-61 micromol/l; p<0.01) and glucose (controls: 5.35+/-0.54 mmol/l;
      skiers: 4.94+/-0.41 mmol/l; p<0.01; cyclists: 4.94+/-0.42 mmol/l; p<0.01). The
      concentration of serum albumin was also decreased in athletes, but the difference
      did not reach statistical significance (controls: 4.76+/-0.26 g/l; skiers: 4.71+/
      0.22 g/l; p=0.384; cyclists: 4.68+/-0.22 g/l; p=0.393). Results of the present
      investigation demonstrate that values of laboratory testing lying outside
      conventional reference limits calculated on sedentary populations might express
      physiological adaptations to regular and demanding physical aerobic activity,
      emphasizing the need for the estimation of reliable reference limits in elite and
      professional athletes, to avoid equivocal interpretation of results within
      clinical and anti-doping contests.

PMID- 15259382
TI  - Low S-adenosylmethionine concentrations found in patients with severe
      inflammatory bowel disease.
AB  - BACKGROUND: S-adenosylmethionine is a methyl donor in many cellular reactions
      including detoxification of constantly produced hydrogen sulphide in the colon. A
      reduced capacity to detoxify hydrogen sulphide may be implicated in the
      pathogenesis of inflammatory bowel disease. S-adenosylmethionine could be low if
      this assumption is correct. We compared S-adenosylmethionine concentrations in
      whole blood in patients with severe and moderate inflammatory bowel disease with
      healthy reference persons. METHODS: S-adenosylmethionine concentrations in whole
      blood were measured using high-pressure liquid chromatography. Patients with
      Crohn's disease (n=21), ulcerative colitis (n=7) and healthy age-matched
      reference persons (or controls) (n=17) were studied. RESULTS: S
      adenosylmethionine concentrations were significantly decreased in patients with
      severe inflammatory bowel disease (mean 1.10 mg/l) as compared to patients with
      moderate Crohn's disease and ulcerative colitis (mean 1.83 mg/l) and reference
      persons (mean 1.84 mg/l). Statistically significant inverse correlations were
      found between S-adenosylmethionine concentration and activity index (p<0.01 and
      R2=0.86) as well as Crohn's disease activity index (p<0.01 and R2=0.50) scores.
      CONCLUSIONS: Low concentrations of S-adenosylmethionine were found in patients
      with severe inflammatory bowel disease. Future studies will show whether S
      adenosylmethionine is a marker for disease activity and a possible tool for
      investigation of sulphur toxicity as a causative mechanism in inflammatory bowel
      disease.

PMID- 15259383
TI  - Reference ranges for two automated chemiluminescent assays for serum insulin-like
      growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3).
AB  - Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP
      3) have become essential tools in the diagnostic work-up of disorders of the
      somatotropic axis in children and adults. The aim of this study was to evaluate
      the automated IMMULITE IGF-I and IGFBP-3 assays and to establish reference limits
      -central 95% intervals, median, 0.1 and other centiles as clinically relevant--as
      a function of age from 797 females and 787 males, from the first week of life
      through the ninth decade. Pubertal children were classified by sex and by sexual
      maturation (Tanner stage). IGF-I and IGFBP-3 levels were also assayed in 20
      pediatric patients each with growth hormone deficiency (GHD) and Turner syndrome
      (UTS), before and during 12 months of recombinant growth hormone (rhGH) therapy,
      as well as in 11 adult patients with GHD and seven with acromegaly before
      therapy. Both the IGF-I and IGFBP-3 assays were accurate, specific and
      sufficiently sensitive to measure IGF-I and IGFBP-3 in serum with good linearity
      and recovery. In the IGF-I assay, potential interference from IGFBPs was
      eliminated by blocking with excess IGF-II. Circulating IGF-I and IGFBP-3
      concentrations, and their ratio IGF-I/IGFBP-3, were age-dependent, showing low
      levels immediately after birth, a typical pubertal peak for girls and boys, and a
      pronounced decline after puberty, reaching a plateau in early adulthood. In
      adults IGF-I and IGFBP-3 levels decreased smoothly but steadily with age.
      Children with GHD and UTS had low circulating IGF-I and IGFBP-3 levels which
      increased to normal reference limits under therapy with rhGH. Adult GHD patients
      showed IGF-I levels below the age-related median; untreated acromegalic patients
      mostly had IGF-I and IGFBP-3 levels above the age-related 97.5th centile. In
      conclusion, the automated IMMULITE IGF-I and IGFBP-3 assays are reliable tools in
      the diagnosis of pathologies of the GH/IGF axis and in the follow-up of their
      therapies.

PMID- 15259384
TI  - The influence of freezer storage of urine samples on the BONN-Risk-Index for
      calcium oxalate crystallization.
AB  - This study was performed to quantify the effect of a 1-week freezer storage of
      urine on its calcium oxalate crystallization risk. Calcium oxalate is the most
      common urinary stone material observed in urolithiasis patients in western and
      affluent countries. The BONN-Risk-Index of calcium oxalate crystallization risk
      in human urine is determined from a crystallization experiment performed on
      untreated native urine samples. We tested the influence of a 1-week freezing on
      the BONN-Risk-Index value as well as the effect of the sample freezing on the
      urinary osmolality. In vitro crystallization experiments in 49 native urine
      samples from stone-forming and non-stone forming individuals were performed in
      order to determine their calcium oxalate crystallization risk according to the
      BONN-Risk-Index approach. Comparison of the results derived from original sample
      investigations with those obtained from the thawed aliquots by statistical
      evaluation shows that i) no significant deviation from linearity between both
      results exists and ii) both results are identical by statistical means. This is
      valid for both, the BONN-Risk-Index and the osmolality data. The differences in
      the BONN-Risk-Index results of both procedures of BONN-Risk-Index determination,
      however, exceed the clinically acceptable difference. Thus, determination of the
      urinary calcium oxalate crystallization risk from thawed urine samples cannot be
      recommended.

PMID- 15259385
TI  - First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay
      -Lp(a) SRM 2B.
AB  - Lipoprotein(a) is an important predictor of cardiovascular disease risk. The lack
      of internationally accepted standardization has impeded the broad application of
      this lipoprotein in laboratory medicine. The International Federation of Clinical
      Chemistry and Laboratory Medicine (IFCC), through its Working Group on
      Lipoprotein(a) and together with research institutions and several diagnostic
      companies, have succeeded in developing an international reference material that
      is intended for the transfer of a lipoprotein(a) concentration to manufacturers'
      master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert
      Committee on Biological Standardization as the 'First WHO/IFCC International
      Reference Reagent for Lipoprotein(a) for Immunoassay'. The assigned unitage of
      0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus
      reference method for lipoprotein(a) and will enable conformity by diagnostic
      companies to the European Union's Directive on In vitro Diagnostic Medical
      Devices for the metrological traceability of calibrator materials.

PMID- 15259386
TI  - Myeloma cells produce sialyl salivary-type amylase.

PMID- 15259387
TI  - Neuropsychological impairment in veterans who are HIV-positive.
AB  - The purpose of this study was to compare the neuropsychological functioning of 12
      veterans who were HIV-positive to 21 age-matched veterans who were HIV-negative.
      Consistent with expectations, the HIV-positive group was found to perform more
      poorly in areas related to attention and concentration, immediate and delayed
      verbal recall, immediate and delayed visual recall, visual learning, and tasks
      requiring psychomotor speed, while a number of language tasks were left intact.
      This was similar to dysfunction often seen in HIV-related dementia cases.
      However, this group was also significantly more impaired in confrontation naming,
      planning, mental calculations, and abstract thought when compared to the HIV
      negative group. Comorbid substance abuse found in the majority of our HIV
      positive subjects was thought to contribute to the HIV-related dysfunction.

PMID- 15259388
TI  - Control of saccades in Parkinson's disease.
AB  - Parkinson's patients (PD) made pro- and antisaccades: In the no-delay condition,
      the target appeared concurrent with the GO signal. In the delay condition, the
      target appeared before the signal for movement. Second, we probed spatial working
      memory in PD. Subjects looked to the remembered locations of sequential targets.
      In the no-delay prosaccade condition, PD had faster reaction times, made more
      express saccades, and exhibited hypometria. In the no-delay antisaccade
      condition, PD had longer reaction times and made more direction errors. In the
      delay tasks, PD made more direction errors and had more difficulty withholding a
      movement. PD made more sequencing errors in the spatial working memory task.
      These findings are consistent with a basal ganglia pathophysiology influencing
      eye movement processing in the frontal cortex.

PMID- 15259389
TI  - The relation between APOE status and neuropsychological memory test performance:
      an analysis of the Canadian Study of Health and Aging.
AB  - This study examined the relationship between two risk factors for dementia, the
      apolipoprotein (APOE) epsilon4 allele and poor memory test performance.
      Participants were from the Canadian Study of Health and Aging, a 4-year
      longitudinal population-based study. Persons with no cognitive impairment who had
      an epsilon4 allele but whose memory was average or better were not at increased
      risk of developing dementia after five years. Risk was increased for those with
      below average memory and no epsilon4 allele, but was particularly increased for
      those with below average memory and an epsilon4 allele. While the APOE epsilon4
      allele was associated with slightly lower memory test performance for persons
      without cognitive impairment at baseline, it only increased their risk of
      developing dementia if their memory was below average.

PMID- 15259390
TI  - "Clockness" in the detection of dementia: a semantic-conceptual effect.
AB  - We studied aspects of clock cognition that might underlie the sensitivity of the
      CDT in screening for dementia of the Alzheimer type (DAT). Two groups, 15
      patients with mild-moderate DAT and 15 controls, were assessed with the CDT and
      specially designed tests of clock-related cognition. Patients were impaired on
      the CDT, but they did not differ from controls in copying a clock face or
      selecting the correct representation of a given time. Patients were worse than
      controls at distinguishing between clock and nonclock objects, detecting
      anomalies in clocks, and in setting time irrespective of response format. These
      findings suggest that semantic-conceptual aspects of clock-related cognition are
      important in discriminating between patients with DAT and controls.

PMID- 15259391
TI  - A case study of strategic infarct dementia investigated with the cognitive
      assessment system.
AB  - Two subjects with brain lesions who were matched on demographic variables were
      tested on the Cognitive Assessment System (CAS). AK had been dependent on
      caregivers after a frontal aneurysm 6 years previously despite intact receptive
      and expressive language skills and motor functions. GM sustained multiple
      infarcts although he continued to function well on his own. Nonparametric
      analysis showed that AK's T scores on CAS subtests were lower than that of GM's
      based on a comparison with a heterogeneous group of brain-damaged patients (p <
      .003). The CAS's broad range of complexity of items within subtests, apparent
      sensitivity in differentiating rates of cognitive decline in dementia, and
      convergence with dementia rating scales suggests that it could be useful for
      assessment of strategic infarct dementia.

PMID- 15259392
TI  - Predictors of cognitive change from preclinical to clinical Alzheimer's disease.
AB  - We examined individual-difference variables in relation to the rate of change in
      global cognitive performance, measured by the MMSE, from 3 years prior to
      diagnosis of Alzheimer's disease (AD) to the time of diagnosis. The population
      based sample consisted of 230 incident AD persons who were followed over a 3-year
      interval. The average annual decline in MMSE was 1.81 points. Being older and
      acquiring additional diseases during the 3 years preceding diagnosis predicted a
      faster rate of decline in global cognitive functioning. However, other individual
      difference variables such as sex, education, depression, vitamin levels (vitamin
      B12 and folic acid), apolipoprotein status, and social network did not
      precipitate the rate of decline in the preclinical phase of AD.

PMID- 15259393
TI  - Changes to the object recognition system in patients with dementia of the
      Alzheimer's type.
AB  - Do DAT patients show category-specific deficits in object identification, and do
      they arise from semantic or visual damage? Participants decided whether line
      drawings of living and nonliving objects matched names at superordinate, basic,
      or subordinate levels. Patients were most impaired with superordinate decisions.
      Controls had most difficulty with subordinate decisions. No category-specific
      deficit was found with patients. Impaired superordinate decisions by the patients
      support semantic damage. If category-specific deficits arise from damaged
      semantics, they should have been found. Since they were not, and since patients
      performed subordinate decisions the best, a visual basis to category specificity
      is supported. Finally, a living advantage was found with normal observers which
      cannot be spurious due to differences in concept familiarity since living and
      nonliving objects were matched for this variable.

PMID- 15259394
TI  - Verbal learning and visuomotor attention in Alzheimer's disease and geriatric
      depression.
AB  - We compared the verbal learning and visuomotor attention of 34 Alzheimer's
      patients and 18 depressive patients. Verbal learning was assessed using The
      Hopkins Verbal Learning Test--Revised (HVLT--R); visuomotor attention was
      assessed using the Trail Making Test (TMT). The Alzheimer's patients had
      significantly lower scores on immediate and delayed recall of a word list. There
      was a nonsignificant trend in this group toward a fewer number of true positives
      and a greater number of false positives. Alzheimer's patients were significantly
      slower on Trails A, with a nonsignificant trend toward slower performance on
      Trails B. No difference was observed in accuracy of attentional processing. The
      results are discussed in terms of other factors, such as stage of cognitive
      decline, which might have influenced the findings.

PMID- 15259395
TI  - In vivo neuroanatomy of Alzheimer's disease: evidence from structural and
      functional brain imaging.
AB  - In vivo structural (CT, MRI) and functional (SPECT, PET) brain imaging techniques
      have been widely used to study the neuroanatomy and neurophysiology of
      Alzheimer's disease (AD) and to identify definite biological markers of the
      disease. We used meta-analytic methods to synthesize this literature to determine
      what neuroanatomical structures best differentiate patients with AD from healthy
      normal controls. A total of 125 studies published between 1984 and 2000 that
      included 3543 patients with AD and 1698 normal healthy controls met inclusion
      criteria. We found that measures of the temporal cortices, including the
      amygdala, hippocampus, and inferior temporal lobes, along with the anterior
      cingulate cortex, associated with the largest magnitudes of effects and, hence,
      could serve as the most useful structures to help clinicians differentiate AD
      from healthy normal aging.

PMID- 15259396
TI  - Encoding and retrieval in aging and memory loss, a fMRI study.
AB  - Mild cognitive impairment (MCI) is a term for nondemented individuals with memory
      complaints and deficits greater than age-adjusted normal performance. Functional
      MRI (fMRI) may be a more sensitive method than other techniques to reveal
      functional abnormalities in individuals with MCI, only a proportion of whom
      progress to Alzheimer's disease (AD). fMRI was carried out while subjects (four
      MCI, five age-matched normal controls, and one AD) performed incidental encoding
      (deep and shallow) and recognition tasks for colored and black and white
      photographs contrasted to baseline fixation. fMRI revealed interesting
      dissociations between activation patterns and behavioral performance when
      comparing the MCI and AD to the NC.

PMID- 15259397
TI  - Cognitive impairment in dementia: correlations with atrophy and cerebrovascular
      disease quantified by magnetic resonance imaging.
AB  - This project assessed the contributions of atrophy and cerebrovascular disease
      (CVD) to cognitive impairment in dementia. Ten individuals with clinically
      diagnosed pure VaD were age-, sex-, and education-matched to individuals with AD.
      All participants underwent neuropsychological testing and MRI which were
      processed to generate quantitative indices of atrophy and CVD. A linear
      regression, including thalamic lesion and vCSF volumes, predicted cognitive
      status (R2 = .74; p < .0005). Three VaD subgroups were identified: thalamic
      lesion (n = 4), hippocampal infarcts (n = 3), and other (n = 3). In participants
      without thalamic lesion, vCSF predicted general cognition (R2 = .48), hippocampal
      atrophy predicted memory impairment (R2 = .33), and white matter lesions
      predicted executive dysfunction (R2 = .48). Both atrophy and CVD burden
      correlated highly with cognitive impairment and should be simultaneously assessed
      in studies of brain-behaviour relations in dementia.

PMID- 15259399
TI  - rCBF/SPECT in the evaluation of inner-city minority patients with a history of
      impaired memory: a pilot blind read pre- and poststudy.
AB  - Eight patients (seven women), mean +/- SD T1 age 68.57 +/- 12.43 years, average
      educational level 5.83 +/- 3.70 years, had two Tc-99m ECD SPECT examinations
      separated by an average 8.49 +/- 5.59 months. Patients were imaged using standard
      Harlem Hospital acquisition and processing protocols with approximately 30 mCi of
      ECD on a Prism 3000 triple head gamma camera. Images were interpreted by an
      independent reader blinded to the patients' clinical history and imaging date. T1
      psychiatric diagnosis was seven Alzheimer's dementia (AD) and one depression.
      Eight T1 images were interpreted as abnormal, six indicative of AD. Binomial 95%
      two-tail confidence interval for T1 agreement between diagnosis and
      interpretation was 0.25 0.63 0.92. T2 diagnosis was seven AD and one none. Seven
      T2 images were abnormal and indicative of AD, and one was normal. T2 confidence
      interval was 0.34 0.75 0.97. These findings suggest SPECT's value in assessing AD
      in uneducated socioeconomically disadvantaged geriatric patients.

PMID- 15259398
TI  - Nicotine and sensory memory in Alzheimer's disease: an event-related potential
      study.
AB  - The auditory mismatch negativity (MMN) event-related brain potential (ERP)
      reflects the storage of information in acoustic sensory memory. Thirteen patients
      with probable Alzheimer's disease (AD), 6 receiving treatment with the
      cholinesterase inhibitor (ChEI) tacrine (tetrahydroaminoacridine, THA) and 7
      receiving no treatment, were administered 2 mg of nicotine polacrilex and
      placebo. MMNs were recorded with 1- and 3-s interstimulus intervals pre- and
      postplacebo/nicotine administration. In nontreated patients, amplitudes were
      decreased from pre- to postplacebo recordings but remained stable in THA-treated
      patients. Comparison of pre- and postnicotine MMNs found amplitude increases with
      nicotine in nontreated but not THA-treated patients. MMN latencies were shortened
      by nicotine in both treatment groups. These exploratory findings suggest that
      nicotine-improved strength of acoustic sensory memory traces and speed of
      acoustic sensory discrimination in AD are differentially affected by chronic ChEI
      treatment.

PMID- 15259400
TI  - Evaluation of prospective memory training for individuals with mild Alzheimer's
      disease.
AB  - Prospective memory (PM) refers to the timely execution of a previously formed
      intention. PM deficits are one of the earliest measurable deficits in Alzheimer's
      disease (AD; Huppert & Beardsall, 1993) and yet, there has been little systematic
      research devoted to identifying ways in which these deficits can be compensated
      for or minimized. In this pilot study, individuals with mild AD participated in a
      new training program aimed at improving PM performance on an experimental PM
      task. PM training consisted of errorless learning and spaced retrieval techniques
      taught in six sessions in subjects' homes. Results showed that compared to
      untrained AD controls. AD patients who received PM training performed a PM task
      successfully across 7 weeks posttreatment (over 90% accuracy; controls 16-33%
      accuracy).

PMID- 15259401
TI  - Therapy for anomia in semantic dementia.
AB  - Semantic dementia is a commonly accepted term for a language disorder resulting
      from neurodegenerative changes due to frontotemporal dementia. An intervention
      program was designed to halt and/or decelerate the effects of progressive anomia
      in AK, a 63-year-old female with semantic dementia. Pictorial stimuli were
      selected and labeled with their respective names and a description most relevant
      to AK's experience. Daily homework assignments were carried out, during which AK
      looked at the picture, read the label aloud, and read the description. Positive
      short-term effects of treatment were observed on treated items.

PMID- 15259402
TI  - Differential memory impairment in dementia with Lewy bodies and Alzheimer's
      disease.
AB  - This study was conducted in order to elucidate the functioning of the Central
      Executive System of Working Memory (WM) and to clarify the status of other
      cognitive functions in Dementia with Lewy bodies (DLB) and Alzheimer's disease
      (AD). Fourteen DLB, 22 AD, and 23 control subjects were assessed with the dual
      task paradigm and other cognitive tests. When compared with controls, DLB
      subjects performed more poorly in concurrent conditions on semantic WM tasks, and
      AD subjects performed more poorly on the spatial WM task. The DLB subjects had an
      inferior verbal span and AD subjects, an inferior recall on the CVLT. These data
      suggest relative impairments of verbal and semantic WM in DLB and relative
      impairments of spatial WM and verbal episodic memory in AD.

PMID- 15259403
TI  - Evidence for a shrinking span of personal and present existence in dementia of
      the Alzheimer's type.
AB  - Severely impaired episodic memory deprives patients with Alzheimer's disease (AD)
      of a sense of personal continuity in their daily lives, yet there are no tests
      that accurately measure this impairment. Recently, Zakzanis, Leach, and
      Moscovitch (1999) examined the integrity of memory function in terms of temporal
      continuity in a way that would engage the patient in everyday behavior, such as
      informal conversation, but still allow memory function to be quantified. The task
      allowed the measurement of the duration of continuous, conscious experience of
      the present and was therefore termed "span of temporal continuity (STC)." Given
      that we were able to document static and growing STCs, we wanted to know whether
      our measure could track progressive memory loss. Accordingly, we followed a
      patient we believed was in the very early stages of AD to measure the change of
      his STC longitudinally. Along with his STC, we present our neuropsychological and
      brain imaging findings over the course of the investigation.

PMID- 15259404
TI  - Noncognitive symptoms in Alzheimer disease and caregivers distress in Chile.
AB  - This study describes the profile of noncognitive symptoms in Chilean AD patients
      and its effects on the caregiver's mental health. In a sample of 26 urban
      dwelling AD patients, 21 of them women, age range 63-90 years, diagnosed using
      NINCDS-ADRDA, the intensity and frequency of noncognitive symptoms and caregivers
      distress was assessed using NPI. Seventeen caregivers were first degree
      relatives. The most prevalent symptoms were apathy, irritability, and anxiety.
      The least were euphoria, hallucinations, and disinhibition. The most stressful
      conditions were disinhibition and agitation: the best well-tolerated were
      euphoria and anxiety. Caregivers responded most frequently with feelings of
      concern and depression. Few of them reported to be ashamed. These results may
      reflect cultural differences and represents the first description of this reality
      in Chile.

PMID- 15259405
TI  - Quality of pasteurised milk and cream produced by on-farm dairies.

PMID- 15259406
TI  - Bloodborne virus infections in dialysis units: a mini-review.

PMID- 15259407
TI  - Improving sexual health--local data are needed to improve local responsiveness.

PMID- 15259408
TI  - Assessment of pasteurisation of milk and cream produced by on-farm dairies using
      a fluorimetric method for alkaline phosphatase activity.
AB  - The alkaline phosphatase test is used as an indicator of adequate pasteurisation
      of milk and cream. A proprietary fluorimetric technique (Fluorophos) is a
      sensitive and quantitative method for the determination of alkaline phosphatase
      (ALP) activity in milk products. Currently, adequate pasteurisation of milk
      products is regarded as confirmed in samples that contain a residual bovine ALP
      activity of < or =500 mU/litre. This is equivalent to the statutory acceptable
      level of 4ug phenol/ml required by the EC analytical method. The purpose of the
      present study was to assess the effectiveness of pasteurisation of milk and cream
      produced by on-farm dairies. In a longitudinal study over a four-year period,
      4,999 samples of milk and cream were collected from 130 on-farm dairies and from
      two large commercial dairies in NW England for comparison. Bovine ALP activity of
      >500 mU/litre was deemed as a failure and was found in 3.5% of whole milk, 2.4%
      semiskimmed milk, 5.0% of skimmed milk, and 39% of cream samples from on-farm
      dairies. Bovine ALP activity of >100 and <500 mU/litre was found in 18.4% of
      whole milk, 9.3% of semi-skimmed milk, 13.2% skimmed milk and 44.5% of cream
      samples from on-farm dairies. Results with skimmed milk samples showed
      significantly lower bovine ALP activity than whole milk. All 409 milk and cream
      samples from two large commercial dairies passed the fluorimetric test at less
      than 500 mU/litre of bovine ALP, and 99% of these milk and cream samples had
      bovine ALP activity of less than 100 mU/litre. The presence of residual bovine
      phosphatase indicates a failure and may be due to either inadequate
      pasteurisation or post pasteurisation contamination with raw milk. Residual
      bovine phosphatase was demonstrated in 108/114 (94.7%) of milk samples with a
      bovine ALP activity greater than 500 mU/litre, i.e. true failures. Of more
      concern is that residual bovine phosphatase was found in 395/401 (98.5%) of
      samples that gave bovine ALP activity greater than 100 mU/litre but equal to or
      less than 500 mU/litre. Residual bovine phosphatase was demonstrated in 37/108
      (30.2%) of cream samples with bovine ALP activity greater than 500 mU/litre.
      Presence of reactivated bovine phosphatase is not an indication of a failure but
      can mask the presence of residual bovine phosphatase. Reactivated bovine
      phosphatase was found in 74/106 (69.8%) of cream samples. Our results confirm
      that the more sensitive fluorimetric method is suitable for testing pasteurised
      whole milk and semiskimmed milk, but for statutory purposes the acceptable level
      of residual bovine phosphatase should be <100 mU/litre. Our findings have
      highlighted a potential problem when testing skimmed milk and cream samples from
      on-farm dairies. To ensure public safety we need more stringent standards for the
      ALP test and new methods that will accurately confirm that pasteurisation of
      these products has been achieved.

PMID- 15259409
TI  - Public health management of a suspected case of rabies.
AB  - A female nurse, recruited from the Philippines five months previously, developed
      meningo-encephalitis and was hospitalised. She was later transferred to a
      hospital in a neighbouring region for specialist treatment. Rabies was part of a
      differential diagnosis and decisions on public health intervention had to be made
      in the absence of a firm diagnosis or clinical history. These decisions centred
      on what infection control measures should be put into effect and when. Issues
      included the leadership and composition of the incident management team, the
      coordination of consistent approaches between the health regions and
      organisations involved, the different priorities of those forming the team and,
      in particular, contacts with the media and meeting public anxieties.

PMID- 15259410
TI  - Audit of rabies post-exposure prophylaxis in England and Wales in 1990 and 2000.
AB  - The objectives were to compare rabies post-exposure prophylaxis issued by the
      Public Health Laboratory Service (PHLS) in 1990 and in 2000, to evaluate their
      appropriateness, and to make recommendations for future issue of rabies post
      exposure prophylaxis in England and Wales. The method was to review all rabies
      vaccine and immunoglobulin issues by PHLS in 1990 and 2000 with evaluation
      against Department of Health recommendations. The PHLS issued prophylaxis to 656
      people in 1990 and 295 people in 2000. The fall is attributable to control
      measures in Western Europe leading to a lower risk of exposure in countries in
      the region. Vaccine was still issued for exposures in countries with a category
      of 'no risk' (15 individuals) including rabies immunoglobulin in six cases.
      Immunoglobulin was frequently not issued for exposures in high-risk countries but
      the reasons were not always evident from the information provided; in many cases
      treatment had probably been started abroad. Delay before contacting the PHLS fell
      between 1990 and 2000 (p = 0.003). Dogs continue to be the most common animal
      exposure reported, and their rabies status is generally unknown. The most
      frequent site of bite was the leg. Prophylaxis was issued for exposure to some
      animals which have never been known to transmit rabies. Successful control
      measures in Europe have reduced the need for rabies prophylaxis in UK residents
      who travel abroad. More detailed information should be collected in future on
      aspects such as pre-exposure vaccination and treatment started abroad to
      facilitate future audit of appropriateness of treatment. A repeat audit should be
      carried out to evaluate the impact of a death from European Bat Lyssavirus 2
      infection in a UK bat handler in November 2002.

PMID- 15259411
TI  - Surveillance of sexually transmitted infections in the West Midlands using
      anonymised individual patient datasets from genitourinary medicine clinics.
AB  - Sexually transmitted infections (STIs) declined in the UK during the 1980s and
      early 1990s but have increased substantially since 1995. Within the overall
      increase there are important differences in the epidemiology of these infections.
      The current, aggregate system of STI data collection in the UK provides limited
      demographic information and is unable to fully explain these differences. More
      useful information can be obtained using an enhanced surveillance system that
      collects disaggregate, anonymised, individual patient data including ethnic group
      and truncated postcode of residence. Such a system has been set up in the West
      Midlands NHS region. The methodology of the project is described here along with
      the findings to date. These findings confirm that the burden of STIs
      disproportionately affects young persons, men who have sex with men, black ethnic
      minority groups and those living in urban areas. Identifying the groups at
      greatest risk in this way enables interventions to be more usefully targeted.

PMID- 15259412
TI  - Do real time 'flu spotter rates warn us about impending emergency admissions and
      deaths?
AB  - This study aimed to determine how general practice influenza surveillance ('flu
      spotter) data related to hospital admissions and deaths in Scotland during the
      winter period. 'Flu spotter rates correlated well with influenza-related
      emergency admissions and deaths, and deaths from all causes, particularly during
      'peak' influenza years. They may be used in a predictive model for influenza
      related hospital admissions and deaths.

PMID- 15259413
TI  - Group A streptococcal bacteraemia in Yorkshire and the Humber: evidence of
      another problematic infection among injecting drug users.
AB  - It has been estimated that in England and Wales, in 2002, 15% of all invasive
      group A streptococcal (GAS) cases were amongst injecting drug users (IDUs). This
      study sought to clarify the extent of this problem in the Yorkshire and Humber
      region by asking laboratories for further information on reported cases. In our
      region we found that there was a near doubling of cases, from 64 reports of GAS
      bacteraemia in the first six months of 2001, to 121 reports in the same period of
      2003. We estimated that 34% of all GAS cases, more than twice the previous
      national estimate, occurred in IDUs and that the proportion of cases occurring in
      IDUs nearly doubled from 2001 to 2002. Our findings should be viewed within the
      context of the increasing reports of several other problematic infections in
      IDUs.

PMID- 15259415
TI  - Outcome for adult contacts of smear-positive pulmonary tuberculosis in the
      absence of X-ray follow-up: 2000-03.
AB  - The effects of the policy change in X-ray follow-up of adult tuberculin-positive
      close contacts of sputum microscopy positive pulmonary tuberculosis made by the
      Joint Tuberculosis Committee of the British Thoracic Society in 2000 were
      monitored prospectively from late 2000 until the end of 2003. No cases in
      contacts that could have been detected by interval X-rays at three and 12 months
      were found. The data, on 291 cases, support the abandonment of X-ray follow-up in
      favour of an 'inform and advise' strategy after an initial normal chest X-ray in
      this category of tuberculosis contact.

PMID- 15259414
TI  - Management of pertussis in a nurse at a special care baby unit.
AB  - A case of pertussis in a nurse at a special care baby unit prompted the
      identification of both neonates and healthcare staff with significant exposure to
      the index case. Respiratory tract samples were collected from all neonates
      involved and prophylactic erythromycin given. Only healthcare staff who developed
      symptoms were investigated and offered treatment. Though no secondary cases were
      identified in this instance, the importance of the early recognition of pertussis
      in adult healthcare workers is highlighted.

PMID- 15259416
TI  - Immunity and exposure to hepatitis A virus in pre-adolescent children from a
      multi-ethnic inner city area.
AB  - Seroprevalence data among ethnic minority groups within England and Wales are
      rare. An opportunistic approach was taken to test residual oral fluid, collected
      from pre-adolescent school children from an ethnically diverse region of
      northwest England, for anti-hepatitis A virus (HAV) IgG. Individual data on
      ethnicity and country of birth were also available. Of the 257 children who
      consented to participate, 62% were of South Asian ethnic origin. The overall
      seroprevalence was 18.8%, higher than 13.1% reported from a recent population
      based survey in England and Wales among a mainly Caucasian population of the same
      age. The only factor significantly associated with HAV seropositivity in a
      multivariable logistic regression model was birth of the child abroad.
      Association with the place of birth of the child, but not that of the parent
      indicates that infection within this group occurs mainly abroad. Larger studies
      among ethnic minority groups are needed to investigate this claim further.

PMID- 15259417
TI  - Prevention of perinatal hepatitis B transmission in a health authority area: an
      audit.
AB  - The aim of this audit was to provide baseline measurement of antenatal hepatitis
      B virus (HBV) screening uptake, coverage of HBV vaccination in infants born to
      high- and low-risk HBsAg carrier mothers, completion of post-vaccination
      serological testing, outcome for vaccinated infants, and an assessment of the
      factors that influenced the effectiveness of the whole programme. Methods
      included identifying HBV positive pregnancies by laboratory results, and follow
      up of at-risk infants by a GP survey. Uptake of antenatal HBV screening was
      99.9%. Thirty-one HBV positive pregnancies were identified, and twenty-nine
      infants were followed up. The overall HBV vaccination completion rate was 93%.
      Fifty per cent of eligible infants were tested for hepatitis carriage, the
      majority of whom were high-risk infants. None had acquired HBV infection and all
      had gained adequate immunity. We conclude that, although the local screening
      programme has been implemented effectively, there is inconsistency in the follow
      up of infants at high and low risk of acquiring HBV.

PMID- 15259418
TI  - Case of cryptic malaria.
AB  - We report a case of falciparum malaria in a renal transplant patient with no
      history of foreign travel. Three weeks previously she had been a hospital
      inpatient with cellulitis and had stayed on the same ward as a man with
      falciparum malaria acquired in Nigeria. There were no cases of malaria in other
      patients on the ward at the same time. The parasites from the two cases were
      genotypically indistinguishable. Despite a thorough investigation, reviewed by an
      expert external panel, no clear route of infection between the cases was
      identified. Patients with malaria should be considered highly infectious by the
      parenteral route. They should be managed with the infection control precautions
      used for patients with bloodborne virus infections. Our case reinforces the need
      for high levels of compliance with universal infection control procedures.

PMID- 15259419
TI  - Why, which, how, who, when? A personal view of smallpox vaccination for the
      2000s.
AB  - The uncertainty about the extent of proliferation of smallpox virus holdings
      since the early 1990s, and particularly whether terrorist groups or so-called
      rogue states might now hold the virus, confronts potential target countries with
      a continuing dilemma. An increasingly large majority of their populations have
      never been vaccinated, and those who have been vaccinated may have become
      susceptible to smallpox again. Yet recent attempts by the United States and other
      governments to persuade large numbers of key personnel and others to accept
      vaccination have at least partially failed and a different long-term strategy is
      needed. This strategy should be based on surveillance of rash illnesses, improved
      public education, more refined contingency planning and a new approach to
      smallpox vaccination. The last should if possible be based on cell-grown, less
      reactogenic vaccines, even though it may be some years before these can become
      available. Meanwhile this article examines other expedients including the use of
      existing lymph vaccines.

PMID- 15259420
TI  - Needle-stick injuries presenting to GP practices across north Wales.

PMID- 15259421
TI  - The behaviour of microbes.
AB  - Viruses and bacteria have complex interactions with their hosts, beyond mere
      replication in them. They range from those that are detrimental, to others that
      may be non-pathogenic or even beneficial. Molecular techniques can help to
      unravel these interactions, sometimes revealing phenomena that benefit host as
      well as microbial populations.

PMID- 15259422
TI  - A standard approach.

PMID- 15259423
TI  - Safe driving for business.
AB  - On the 1 December 2003 a new law came into effect banning the use of hand held
      mobile telephones whilst driving. This article looks at the background to this
      new law, considers whether business drivers should be provided with hands free
      telephones and offers assistance for organisations that wish to develop a safe
      driving policy for their staff.

PMID- 15259424
TI  - Psychological, neuropsychological, and electrocortical effects of mixed mold
      exposure.
AB  - The authors assessed the psychological, neuropsychological, and electrocortical
      effects of human exposure to mixed colonies of toxigenic molds. Patients (N =
      182) with confirmed mold-exposure history completed clinical interviews, a
      symptom checklist (SCL-90-R), limited neuropsychological testing, quantitative
      electroencephalogram (QEEG) with neurometric analysis, and measures of mold
      exposure. Patients reported high levels of physical, cognitive, and emotional
      symptoms. Ratings on the SCL-90-R were "moderate" to "severe," with a factor
      reflecting situational depression accounting for most of the variance. Most of
      the patients were found to suffer from acute stress, adjustment disorder, or post
      traumatic stress. Differential diagnosis confirmed an etiology of a combination
      of external stressors, along with organic metabolically based dysregulation of
      emotions and decreased cognitive functioning as a result of toxic or metabolic
      encephalopathy. Measures of toxic mold exposure predicted QEEG measures and
      neuropsychological test performance. QEEG results included narrowed frequency
      bands and increased power in the alpha and theta bands in the frontal areas of
      the cortex. These findings indicated a hypoactivation of the frontal cortex,
      possibly due to brainstem involvement and insufficient excitatory input from the
      reticular activating system. Neuropsychological testing revealed impairments
      similar to mild traumatic brain injury. In comparison with premorbid estimates of
      intelligence, findings of impaired functioning on multiple cognitive tasks
      predominated. A dose-response relationship between measures of mold exposure and
      abnormal neuropsychological test results and QEEG measures suggested that toxic
      mold causes significant problems in exposed individuals. Study limitations
      included lack of a comparison group, patient selection bias, and incomplete data
      sets that did not allow for comparisons among variables.

PMID- 15259425
TI  - Neural autoantibodies and neurophysiologic abnormalities in patients exposed to
      molds in water-damaged buildings.
AB  - Adverse health effects of fungal bioaerosols on occupants of water-damaged homes
      and other buildings have been reported. Recently, it has been suggested that mold
      exposure causes neurological injury. The authors investigated neurological
      antibodies and neurophysiological abnormalities in patients exposed to molds at
      home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling,
      tremors, and muscle weakness in the extremities). Serum samples were collected
      and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for
      antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside
      GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin,
      chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and
      mycotoxins were also determined with ELISA, as reported previously.
      Neurophysiologic evaluations for latency, amplitude, and velocity were performed
      on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and
      amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with
      documented, measured exposure to molds had elevated titers of antibodies
      (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve
      conduction studies revealed 4 patient groupings: (1) mixed sensory-motor
      polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3)
      sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no
      neurophysiological abnormalities (n = 20, normal controls). All groups showed
      significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG)
      of antibodies to neural antigens when compared with 500 healthy controls. Groups
      1 through 3 also exhibited abnormal neurophysiologic findings. The authors
      concluded that exposure to molds in water-damaged buildings increased the risk
      for development of neural autoantibodies, peripheral neuropathy, and
      neurophysiologic abnormalities in exposed individuals.

PMID- 15259426
TI  - Studies on the role of fungi in Sick Building Syndrome.
AB  - Sick Building Syndrome is a term used to describe symptoms in humans which result
      from problems with indoor air quality. Common complaints include dyspnea, flu
      like symptoms, watering eyes, and allergic rhinitis. Although there is likely no
      single cause for Sick Building Syndrome, fungal contamination in buildings has
      increasingly been associated with this spectrum of symptoms. The authors describe
      2 case studies, and other experimentation, that have investigated the role of
      fungi in the occurrence of Sick Building Syndrome.

PMID- 15259427
TI  - Analysis for mycotoxins: the chemist's perspective.
AB  - Mycotoxins are fungal metabolites that pose a health risk to exposed animals and
      humans. In recent years, concern has mounted regarding human exposure to
      mycotoxins via inhalation of mold spores produced in damp buildings and homes.
      Although mycotoxins can be detected in such buildings, reliable means for
      measuring an occupant's level of exposure to most mycotoxins are lacking. The
      author briefly reviews the chemical methods currently available for mycotoxin
      analysis, outlining accepted practices and discussing the limitations of these
      measurements.

PMID- 15259428
TI  - Organophosphorus ester-induced chronic neurotoxicity.
AB  - Organophosphorus compounds are potent neurotoxic chemicals that are widely used
      in medicine, industry, and agriculture. The neurotoxicity of these chemicals has
      been documented in accidental human poisoning, epidemiological studies, and
      animal models. Organophosphorus compounds have 3 distinct neurotoxic actions. The
      primary action is the irreversible inhibition of acetylcholinesterase, resulting
      in the accumulation of acetylcholine and subsequent overstimulation of the
      nicotinic and muscarinic acetylcholine receptors, resulting in cholinergic
      effects. Another action of some of these compounds, arising from single or
      repeated exposure, is a delayed onset of ataxia, accompanied by a Wallerian-type
      degeneration of the axon and myelin in the most distal portion of the longest
      tracts in both the central and peripheral nervous systems, and is known as
      organophosphorus ester-induced delayed neurotoxicity (OPIDN). In addition, since
      the introduction and extensive use of synthetic organophosphorus compounds in
      agriculture and industry half a century ago, many studies have reported long
      term, persistent, chronic neurotoxicity symptoms in individuals as a result of
      acute exposure to high doses that cause acute cholinergic toxicity, or from long
      term, low-level, subclinical doses of these chemicals. The author attempts to
      define the neuronal disorder that results from organophosphorus ester-induced
      chronic neurotoxicity (OPICN), which leads to long-term neurological and
      neurobehavioral deficits. Although the mechanisms of this neurodegenerative
      disorder have yet to be established, the sparse available data suggest that large
      toxic doses of organophosphorus compounds cause acute necrotic neuronal cell
      death in the brain, whereas sublethal or subclinical doses produce apoptotic
      neuronal cell death and involve oxidative stress.

PMID- 15259429
TI  - Atmospheric transport of mold spores in clouds of desert dust.
AB  - Fungal spores can be transported globally in clouds of desert dust. Many species
      of fungi (commonly known as molds) and bacteria--including some that are human
      pathogens--have characteristics suited to long-range atmospheric transport. Dust
      from the African desert can affect air quality in Africa, Europe, the Middle
      East, and the Americas. Asian desert dust can affect air quality in Asia, the
      Arctic, North America, and Europe. Atmospheric exposure to mold-carrying desert
      dust may affect human health directly through allergic induction of respiratory
      stress. In addition, mold spores within these dust clouds may seed downwind
      ecosystems in both outdoor and indoor environments.

PMID- 15259430
TI  - The way we build now.
AB  - Vernacular building for humans evolved in much the same way that shelter evolved
      for birds and animals: largely by trial and error, and experience. Healthy
      accommodation is critical for the survival of all species, and the existence of
      molds and fungal spores in the air and food supply has been part of the
      evolutionary equation. With human intervention, the environment has been changed
      by the use of chemical products and the availability of cheap energy, at a rate
      outpacing evolutionary adaptation. The interaction of these challenges with
      building design and human health is significant. Relevant factors should be
      explored, and their effects understood, so that solutions in building can be
      developed before the use of fossil fuels must be abandoned altogether.

PMID- 15259431
TI  - Proactive approaches for mold-free interior environments.
AB  - Interior design education and practice can contribute to the prevention of mold
      growth in indoor environments. The authors provide an overview of current
      thinking within the interior design educational and professional communities
      regarding proactive approaches to achieving mold-free building interiors,
      including identification of current best practices for the prevention of mold
      problems in buildings. They also discuss the development of certification
      programs. A review of recent literature points to the need for interior designers
      to be educated to specify the use of ecologically sound materials that support
      the health of building occupants. The authors present trade-offs between best
      practices for designing mold-free indoor environments (including considerations
      of cost, maintenance, and operation) and occupant comfort, health, and well
      being.

PMID- 15259432
TI  - Creating mold-free buildings: a key to avoiding health effects of indoor molds.
AB  - In view of the high costs of building diagnostics and repair subsequent to water
      damage--as well as the large medical diagnostic and healthcare costs associated
      with mold growth in buildings--commitment to a philosophy of proactive preventive
      maintenance for home, apartment, school, and commercial buildings could result in
      considerable cost savings and avoidance of major health problems among building
      occupants. The author identifies common causes of mold growth in buildings and
      summarizes key building design and construction principles essential for
      preventing mold contamination indoors. Physicians and healthcare workers must be
      made aware of conditions within buildings that can give rise to mold growth, and
      of resulting health problems. Timely advice provided to patients already
      sensitized by exposure to molds could save these individuals, and their families,
      from further exposures as a result of inadequate building maintenance or an
      inappropriate choice of replacement housing.

PMID- 15259433
TI  - Lipoic acid as a potential first agent for protection from mycotoxins and
      treatment of mycotoxicosis.
AB  - Mycotoxins--toxic substances produced by fungi or molds--are ubiquitous in the
      environment and are capable of damaging multiple biochemical mechanisms,
      resulting in a variety of human symptoms referred to collectively as
      "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with
      respect to their ultimate damage, but also in their routes of detoxification.
      This suggests potential therapeutic options for the challenging treatment of
      mycotoxicosis. In this brief review, the author examines the use of lipoic acid
      as an example of an inexpensive and available nutrient that has been shown to
      protect against, or reverse, the adverse health effects of mycotoxins.

PMID- 15259434
TI  - Treatment of cancer with mushroom products.
AB  - Cancer has been attributed to 3 causes: pollution, infection, and poor nutrition.
      Conventional treatments include surgery, chemotherapy, and radiotherapy. The
      author proposes that immunotherapy also be considered. Among other environmental
      influences, dietary deficiencies and carcinogenic viral infections must be
      investigated and treated wherever possible. It has been suggested that mushrooms,
      in particular, have a structure that is immunomodulatory because it resembles the
      proteoglycan structure in the human extracellular matrix, and both are
      metabolically active. Inasmuch as mitochondria have a bacterial origin,
      proteoglycans may have a mushroom origin. The author describes a study which
      shows that natural killer cells can double in number with 8 wk of treatment with
      Coriolus versicolor. Also described is an epidemiological survey of cancer deaths
      among Flammulina velutipes farmers in Japan, which found that the mushroom
      farmers had lower rates of cancer deaths than controls who were not involved in
      mushroom farming.

PMID- 15259435
TI  - Summary of the 5th International Conference on Bioaerosols, Fungi, Bacteria,
      Mycotoxins, and Human Health.
AB  - Risk assessment of bioaerosols indoors has been summarized in terms of human
      health effects (e.g., allergy, infection, and irritation), but neurotoxicity has
      been a topic of heated debate <fseif@esceng.com>. However, this debate has been
      resolved rather clearly by evidence presented at this conference (and at the 21st
      Annual International Symposium on Man and His Environment in Health and Disease,
      Dallas, Texas, June 2003) which showed that neurotoxicity, as well as pulmonary
      and immune dysfunction, can result from exposure to molds in the indoor
      environment. Toxicity is apparent, and confirming studies are being published.
      For more information regarding the conference, visit
      <http://www.bioaerosol.org/index.html>. For details on the research summarized
      herein, please contact the presenting authors via their e-mail addresses. This
      reference system should aid in the dissemination of information that is current
      but not yet published.

PMID- 15259436
TI  - This regulator works for the governator.

PMID- 15259437
TI  - One hospital's dubious approach to reducing uncompensated care.

PMID- 15259438
TI  - Compensation monitor. Providers retain upper hand over health plans.

PMID- 15259439
TI  - The new consensus favoring IOM's definition of quality.

PMID- 15259441
TI  - Some plans take advantage of managed Medicare redux.

PMID- 15259440
TI  - P&T committees in position to reduce medication errors.

PMID- 15259442
TI  - Health plans respond as microbes develop resistance techniques.

PMID- 15259443
TI  - The formulary files. Use of attention-deficit medications surges 369 percent in
      children under 5.

PMID- 15259444
TI  - Welcome to the brave, new (electronic) world, doctor.

PMID- 15259445
TI  - Laronidase opens door to treat other rare disorders.

PMID- 15259446
TI  - CDC begins to provide resources for workplace wellness programs.

PMID- 15259447
TI  - Managed care outlook. The bigger they (MCOs) are, the better they'll do.

PMID- 15259448
TI  - Coagulation, inflammation and myocardial dysfunction in unstable coronary artery
      disease and the influence of glycoprotein IIb/IIIa inhibition and low molecular
      weight heparin.
AB  - Patients with unstable coronary artery disease (CAD) have an increased risk of
      subsequent myocardial infarction and death. This study evaluated the safety and
      efficacy of treatment with glycoprotein IIb/IIIa inhibition in addition to
      aspirin, low molecular-weight heparin and its influence on coagulation and
      inflammation. Also, early and differentiated risk assessment utilising markers of
      inflammation, myocardial damage and dysfunction were evaluated. The Global
      Utilisation of Strategies To open Occluded arteries-IV (GUSTO-IV) trial
      randomised 7800 patients with unstable CAD to 24 or 48 hours infusion of
      abciximab or placebo in addition to routine treatment with aspirin and heparin or
      dalteparin. Baseline levels of creatinine, C-reactive protein (CRP), troponin T
      (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. At
      selected sites, all patients received subcutaneous dalteparin (n=974), in stead
      of heparin infusion (n=6826). In a sub-population of dalteparin treated patients
      (n=404), serial measurements of markers of coagulation, fibrinolysis and
      inflammation were also performed. Addition of abciximab to dalteparin as the
      primary treatment of unstable CAD was not associated with any significant
      reduction in cardiac events but a doubled risk of bleedings. The combination of
      abciximab with dalteparin seemed as safe when used with heparin. Despite full
      dose dalteparin and aspirin there was a simultaneous activation of the
      inflammation, coagulation and fibrinolysis systems without any influence of the
      abciximab treatment. Elevated levels of CRP, TnT, and NT-proBNP and reduced
      creatinine clearance were independently related to short and long-term mortality.
      The best prediction of high and low risk was provided by a combination of NT
      proBNP and creatinine clearance. Any detectable elevation of TnT and reduced
      creatinine clearance, but neither elevation of CRP nor NT-proBNP, were also
      independently associated to a raised risk of subsequent myocardial infarction.

PMID- 15259449
TI  - A two- stage surgery for severe femoral neck deformity due to fibrous dysplasia:
      a case report.
AB  - Various kinds of surgical treatments have been reported for varus deformity of
      the proximal femur due to fibrous dysplasia. We report a case of two-stage
      corrective osteotomy for severe varus-retroversion deformity of the femoral neck
      due to monostotic fibrous dysplasia. The patient was an 18 year-old man. On
      initial examination, the spina malleollar distance was 88 cm on the right side
      and 83 cm on the left. Plain radiography showed prominent varus deformity of his
      left proximal femur. The morphology was 130 degrees on the right side and 85
      degrees on the left. Computed tomography revealed 60 degree retroversion of the
      femoral neck. A two-stage surgery was performed, consisting of curettage and bone
      grafting followed by corrective osteotomy 16 months later. A 55 degree valgus
      osteotomy was performed in the subtrochanteric region. After osteotomy and 40
      degree internal rotation of the shaft, a 130 degree angle plate was used for
      osteosynthesis. Postoperative radiological examination showed a morphology of 140
      degrees and computed tomography revealed a 20 degree retroversion of the femoral
      neck. No recurrence or varus deformity was seen at four years after surgery.
      Although the leg length discrepancy was 2.5 cm, the patient had no difficulty in
      one foot standing and no restriction of ADL (activity of daily living). The well
      known progressive varus Shepherd's crook deformity in the polyostotic form of
      fibrous dysphasia is associated with limb shortening, limping, and occasionally
      chronic fatigue fractures with disabling pain. Various kinds of surgical
      treatments have been reported for this type of varus deformity. Curettage and
      bone grafting is one of the most common and simple treatments. However, this
      method often gives bad results as the grafted bones are absorbed and that the
      progress of varus deformity van not to be prevented. We report a case of two
      stage corrective osteomy forsevere varus-retroversion deformity of the femoral
      neck due to monostotic fibrous dysplasia.

PMID- 15259450
TI  - Field distribution of compound muscle action potentials of the calf muscles in
      rabbits.
AB  - The purpose of this study is to verify that compound muscle action potentials
      (CMAPs) generated a stationary potential and to examine extension of the CMAPs
      away from the stimulated muscle. A referential derivation and/or bipolar
      derivation to record the stationary potentials were carried out following tibial
      nerve stimulation at the popliteal fossa in 10 rabbits. After recording a bipolar
      and/or referential derivation, wave changes were monitored before and after
      severing the tibial nerve. The change of the wave by compressing or direct
      electrical stimulation to the calf muscle was also monitored. In referential
      derivatives, the stationary waves were observed on top of the skull in all the
      rabbits examined with the peak latency of the potentials from 3.78 msec to 5.04
      msec. In bipolar derivations, the upper limits of the stationary waves recorded
      were the trunks. The peak latencies were from 2.35 msec to 5.46 msec with an
      average of 4.12 msec. By analyzing the results from severing the tibial nerves,
      compressing the calf muscles, and direct electrical stimulation of the calf
      muscle, the origin of these stationary potentials was determined to be CMAPs of
      the calf muscles. These findings suggest contamination of the stationary
      potentials originated by CMAPs for recording of any evoked potentials when motor
      nerves are stimulated.

PMID- 15259451
TI  - Using the MEDLINE database to study the concept of urinary tract infections in
      different domains of medicine.
AB  - As a way of exploring differences between medical domains regarding management of
      urinary tract infections, we investigated the MEDLINE database for differences in
      indexing patterns. Further, our intention was to assess the MEDLINE database as a
      source for studying medical domains. We examined the use of main headings,
      subheadings and the level of main headings in six medical domains that manage
      urinary tract infections. Many intuitive but also some counterintuitive results
      were found indicating that the MEDLINE database is difficult to use for studying
      medical domains mainly due to unclear semantics both in the headings and the
      indexing process, which results in variability in indexing. This variability
      probably hides significant results. We also conclude that the differences found
      indicate that in addition to differences between domains, there are also large
      variations within domains.

PMID- 15259452
TI  - Obesity related measurements and joint space width in patients with knee
      osteoarthritis.
AB  - BACKGROUND: The aim of this study is to analyze the relationship between body
      mass index and obesity related measurements and tibiofemoral joint space which
      have been the principal method of radiographic evaluation in progression and
      therapeutic trials of knee osteoarthritis. METHODS: Fifty-five female patients
      with the diagnosis of osteoarthritis in knees according to the criteria of
      American College of Rheumatology in knees were included in the study. The mean
      age of patients was 57,42+/-8,60(SD) years with a range of 42-77. Medial and
      lateral compartment joint space widths were measured on antero-posterior knee
      radiography. Body mass index, triceps, biceps, subscapular and suprailiac
      skinfold thickness, waist and hip circumference were measured. Body composition
      was determined by dual energy X-ray absorpsiometry (DEXA) (Norland XR 46) and
      total lean mass (g), total fat mass (g), trunk lean mass, trunk fat mass, abdomen
      lean mass, abdomen fat mass measurements were recorded. RESULTS: Patients with
      body mass index>30 were accepted as obese patients. According to these criteria
      33 of the 55 patients were obese. Tibial medial compartment and tibial lateral
      compartment measurements of obese patients were significantly lower than nonobese
      patients (p=0,000, p=0,003 respectively). Body mass index was correlated with
      total lean mass, total fat mass, trunk fat mass, abdominal fat mass, leg fat
      mass. Tibial medial compartment and tibial lateral compartment space measurements
      were negatively correlated with body mass index. CONCLUSION: Our results revealed
      significant difference in both medial and lateral joint spaces of obese and
      nonobese patients with knee osteoarthritis. Medial and lateral joint spaces of
      obese patients were narrower than nonobese osteoarthritis patients. The more body
      mass index had the patients the narrower joint space they had displayed. However
      body composition analysis and obesity related measurements did not show
      additional correlation with tibial compartment measurement.

PMID- 15259453
TI  - Is there an association between rumination and self-reported physical health? A
      one-year follow-up in a young and an elderly sample.
AB  - Cross-sectional studies have suggested an association between rumination and
      subjective health. The aim of the present study was to investigate in a
      longitudinal design whether rumination was related to self-reported physical
      health. A total of 96 young (age range 20-35) and 110 elderly (age range 70-85)
      participants completed questionnaires measuring rumination, negative affect, life
      events, and self-reported physical health at baseline and at 1-year follow-up.
      Multiple linear regressions showed a significant association between self
      reported physical health at time I only for the elderly and negative affect
      mediated the association. At follow-up, rumination was significantly associated
      with self-reported physical health only for the young and the association was
      only partly mediated by negative affect. In conclusion, rumination is associated
      with poorer self-reported physical health, but the association depends on the age
      of the individual as well as time span studied.

PMID- 15259454
TI  - Spousal support satisfaction as a modifier of physiological responses to marital
      conflict in younger and older couples.
AB  - We investigated linkages between spousal support satisfaction and affective,
      cortisol, and blood pressure responses to conflict in two samples, 85 newlyweds
      and 31 older couples, married an average of 42 years. Couples were admitted to a
      hospital research unit and provided self-reports regarding the support received
      from their spouses. After a baseline period, couples engaged in a 30-min conflict
      discussion during which time blood was drawn for cortisol assessment. After the
      conflict, newlyweds' blood pressure was measured. Among newlywed wives, greater
      spousal support satisfaction was associated with smaller changes in negative
      affect and cortisol responses to conflict. Notably, newlywed wives and husbands
      demonstrated lower blood pressure after conflict when spousal support
      satisfaction was higher. In contrast, older husbands (but not wives) exhibited
      greater cortisol responses when spousal support satisfaction was lower. These
      relationships provide a window on mechanisms linking marriage and health for men
      and women across the life span.

PMID- 15259455
TI  - The stress of being chronically ill: from disease-specific to task-specific
      aspects.
AB  - The assumption that disease-related stressors are exclusive for particular
      diagnoses characterizes many studies of chronically ill patients. In this study
      the perceptions of 1305 patients from 10 different chronic disease categories
      were compared with respect to a number of important stressors. Differences were
      found in the amount and type of stressors experienced, but these differences
      could not solely be explained by type of disease. Personal characteristics such
      as age, sex, education level, living situation, and illness duration were also
      important in determining the degree and type of stress experienced. The
      implications of these findings for stress/coping research as well as the clinical
      implications are discussed.

PMID- 15259456
TI  - Understanding soft drink consumption among male adolescents using the theory of
      planned behavior.
AB  - This study identified factors that influence regular soda consumption among 564
      male students, aged 13-18 years, attending North Los Angeles County public high
      schools. Participants completed a group-administered Theory of Planned Behavior
      based questionnaire. Almost all of the participants, 96.5%, reported that they
      currently drink soda, 60.2% reported drinking two glasses of soda or more per day
      during the past year. Students reported drinking regular soda more than diet soda
      and reported drinking phosphoric acid containing soda (cola) more than
      nonphosphoric acid containing soda (noncola). Attitude, subjective norm, and
      perceived behavioral control were significant predictors of intention to drink
      regular soda and together explained 61% of its variance. Our results suggest that
      parents, teachers/coaches, and health professionals should encourage the
      perception that there are other healthier drinks that quench thirst better than
      soft drinks and taste good, and that soda should not be excessively available at
      home.

PMID- 15259457
TI  - The PedsQL in pediatric asthma: reliability and validity of the Pediatric Quality
      of Life Inventory generic core scales and asthma module.
AB  - The PedsQL is a modular instrument designed to measure health-related quality of
      life (HRQOL) in children and adolescents ages 2-18. The PedsQL 4.0 Generic Core
      Scales were developed to be integrated with the PedsQL Disease-Specific Modules.
      The PedsQL3.0 Asthma Module was designed to measure pediatric asthma-specific
      HRQOL. The PedsQL was administered to 529 families. Internal consistency
      reliability was demonstrated for the PedsQL 4.0 Total Score (alpha = 0.90 child,
      0.91 parent report) and Asthma Module (average alpha = 0.71 child, 0.86 parent
      report). The PedsQL 4.0 distinguished between healthy children and children with
      asthma. The validity of the PedsQL Asthma Module was demonstrated through
      intercorrelations with a previously standardized asthma disease- specific
      instrument. Responsiveness was demonstrated through patient change over time as a
      result of clinical intervention. The results demonstrate the reliability,
      validity, and responsiveness of the PedsQL required for an outcome measure in
      pediatric asthma clinical trials and research.

PMID- 15259458
TI  - The effects of untreated bednets on malaria infection and morbidity on the Kenyan
      coast.
AB  - A study was conducted in order to determine whether children that slept under
      untreated bednets were protected against both malaria infection and clinical
      disease compared with children not sleeping under bednets. The study was
      conducted in Kilifi District, Kenya, during the malaria season (June-August,
      2000) and involved 416 children aged < or = 10 years. Data collected from a cross
      sectional survey showed evidence of protection against malaria infection among
      children sleeping under untreated bednets in good condition compared with those
      not using nets (adjusted odds ratio [AOR] = 0.4, 95% CI 0.22-0.72, P = 0.002).
      There was no evidence of a protective effect against infection when comparing
      those that used untreated bednets that were worn and those not using nets (AOR =
      0.75, 95% CI 0.34-1.63, P = 0.47). When these same children were followed-up
      during the malaria season, there was evidence of a lower rate of clinical malaria
      among those that used untreated nets in good condition (adjusted incidence rate
      ratio = 0.65, 95% CI 0.45-0.94, P = 0.022), while the rate of clinical malaria
      among those that used untreated bednets that were worn was similar to that of
      those that did not use bednets. In the face of persistent failure of communities
      to take up net retreatment, there is hope that untreated nets will offer some
      protection against malaria infection and disease compared with not using nets at
      all.

PMID- 15259459
TI  - No effect of recall period length on prevalence of self-reported haematuria in
      Schistosoma haematobium-endemic areas.
AB  - Assessing prevalence of haematuria by interview is commonly used as a rapid
      method to identify communities for mass treatment of Schistosoma haematobium
      infection. We analysed, using 21 published studies, to what extent the prevalence
      estimates of haematuria were affected by the length of the recall period for
      which respondents were requested to report symptoms. There was a strong positive
      association between prevalence of haematuria and infection, but no effect of
      recall period length. This suggests that the choice of recall period is of minor
      importance in control programmes or studies based on reported haematuria.

PMID- 15259461
TI  - Sri Lankan cutaneous leishmaniasis is caused by Leishmania donovani zymodeme MON
      37.
AB  - Sri Lankan cutaneous leishmaniasis (CL), once considered sporadic, is fairly
      widespread in some parts of the country. Identification of 5 isolates from 4 CL
      patients by enzyme analysis during 2002 showed that they were all Leishmania
      donovani zymodeme MON-37, the parasite which also causes visceral leishmaniasis
      in India and East Africa.

PMID- 15259460
TI  - Transmission of Plasmodium falciparum in urban Yaounde, Cameroon, is seasonal and
      age-dependent.
AB  - Data on malaria transmission intensity and prevalences of asexual parasites and
      of gametocytes were obtained in an urban district of Yaounde, Cameroon. The
      transmission level from mosquito to human was determined by indoor night capture
      of mosquitoes on human volunteers, revealing a calculated entomological
      inoculation rate of 34 infectious bites per person per year. Only Anopheles
      gambiae and A. funestus contributed to malaria transmission and their
      distribution was seasonal. Cross-sectional surveys every 2 months from July 1999
      to May 2000 (n = 965) showed average annual prevalences of 35% Plasmodium
      falciparum asexual parasites (range 29-38%) and 4.4% gametocytes (range 0-6.7%).
      Prevalence of high parasitaemia (> 400 parasites/microL) and of gametocytes was
      seasonal. Prevalence of asexual parasitaemias and of gametocytaemias was age
      dependent. The potential infectious reservoir in this area is dominated by the
      age group 0-15 years, representing 75% of carriers of asexual parasites (P <
      0.001), 85% of carriers of high parasitaemias (P < 0.001), and 83% of gametocyte
      carriers (P = 0.03). Full year logistic models developed from the available data
      accurately predicted parasite prevalences in subsequent analyses, thus permitting
      a precise determination of study samples for intervention and seroepidemiology
      studies, and analysis of the infectious reservoir in this area.

PMID- 15259462
TI  - Prevalence and risk factors associated with Helicobacter pylori infection in
      native populations from Brazilian Western Amazon.
AB  - We evaluated the prevalence of, and factors associated with, Helicobacter pylori
      infection in 222 subjects from 3 distinct communities of native populations (Uru
      Eu-Wau-Wau Indians and 2 riverine communities living on the banks of the Machado
      river and in Portuchuelo) living in isolation in the rainforest of Brazilian
      Western Amazon. The overall prevalence was 78.8% (95% CI 72.7-83.9). The
      prevalence was higher in the Machado river community compared with Portuchuelo
      (chi2 = 3.84, P = 0.05), but no significant difference was observed between the
      Machado river community and the Uru-Eu-Wau-Wau Indians. Logistic regression
      showed that residential crowding and age were factors associated with the
      presence of H. pylori infection. Acquisition of the bacterium started early in
      life and by the age of 2 years 50% of children were infected. The prevalence
      increased with age, reaching near universal levels during adulthood (97.9%).
      Residential crowding was high with a global index of 3.3 persons/room (SD = 1.8),
      varying significantly between the 3 communities (P = 0.001). These data provide
      further evidence supporting direct person-to-person spread of the bacterium.

PMID- 15259464
TI  - Detection of circulating Leishmania chagasi DNA for the non-invasive diagnosis of
      human infection.
AB  - A polymerase chain reaction (PCR) assay for the detection of Leishmania spp. DNA
      in peripheral blood was optimized and evaluated for the diagnosis of human
      visceral leishmaniasis (VL) in Brazil during May 2001 to December 2002.
      Optimization of the technique resulted in a detection limit of 1.65 fg of
      purified L. (L.) chagasi DNA, equivalent to 1.65 x 10(-2) parasites. Leishmania
      DNA was detected in the blood of 48 of 53 patients with parasitologically
      confirmed VL, which corresponds to a sensitivity of 91%. No DNA was detected in
      the peripheral blood of 15 healthy, non-exposed volunteers, giving a specificity
      of 100%. We conclude that detection of parasite DNA in peripheral blood offers a
      non-invasive, sensitive and rapid method for the detection of VL caused by L.
      (L.) chagasi.

PMID- 15259463
TI  - Simultaneous identification of the four human Plasmodium species and
      quantification of Plasmodium DNA load in human blood by real-time polymerase
      chain reaction.
AB  - The incidence of imported malaria cases in travellers returning from endemic
      areas has considerably increased over the last few years. The microscopical
      examination of stained blood films is the gold standard method to confirm
      clinical suspicion of malaria but diagnosis is difficult in the case of mixed
      infections, low-grade parasitaemia, or forms altered by uncompleted treatment. We
      have developed a real-time polymerase chain reaction (PCR) for the simultaneous
      identification of the 4 human Plasmodium spp. and quantification of Plasmodium
      DNA in human blood. The rapid turnaround and reduction in the risk of PCR product
      carryover are major advantages compared with conventional PCR. In combination
      with conventional tests, this method could be a powerful tool for the diagnosis
      of malaria infections among travellers from endemic areas and during the follow
      up of patients in reference centres involved in travel and tropical medicine.
      Quantitative real-time PCR could also be used for the follow-up of patients
      during drug resistance studies managed by national malaria programmes, the
      testing of new drugs, and vaccine trials.

PMID- 15259465
TI  - Evaluation of newer diagnostic methods for the detection and differentiation of
      Entamoeba histolytica in an endemic area.
AB  - We evaluated the colorimetric polymerase chain reaction (PCR)-based method for
      the detection and differentiation of Entamoeba spp. and compared the efficacy of
      E. histolytica-specific antigen detection in faeces with the detection of
      specific antibodies to E. histolytica-specific antigen in faeces, by enzyme
      linked immunosorbent assay. Faecal samples were obtained from patients attending
      hospital in Chandigarh, India, from March 2001 to February 2002. The PCR-based
      colorimetric method was found to be the most sensitive (100%) and it could
      differentiate between pathogenic and non-pathogenic Entamoeba spp. The present
      study also emphasized that the antigen detection system may prove to be a better
      diagnostic tool than the antibody detection system in endemic areas.

PMID- 15259466
TI  - Epidemiology of Strongyloides stercoralis in north-east Thailand: application of
      the agar plate culture technique compared with the enzyme-linked immunosorbent
      assay.
AB  - Cross-sectional surveys of parasitic infection were performed using the agar
      plate culture technique (APCT) and modified formalin-ethyl acetate concentration
      technique (MFECT) to assess the true prevalence of Strongyloides stercoralis
      relative to other parasites in north-east Thailand. The enzyme-linked
      immunosorbent assay (ELISA) for diagnosis of S. stercoralis infection was used to
      estimate the seroprevalence for comparison with coproprevalence. Faecal and serum
      samples were collected from study participants during October-November 2000.
      Within the sample population of 332 rural northeast Thais from 3 communities, S.
      stercoralis was the most common parasitic infection (average 28.9%, range 27.7
      30.3%) as determined by APCT; by MFECT the average was 5.4% (range 1.8-8.6%).
      Other intestinal parasites by order of prevalence were Opisthorchis viverrini
      (average 14.2%, range 8.6-19.4%), hookworm (average 12.3%, range 4-20.2%),
      Echinostoma sp. (7.5%), Giardia intestinalis (0.9%), Trichuris trichiura (0.6%),
      and Taenia sp., Hymenolepis nana and Entamoeba coli (all 0.3%). In an analysis of
      a subset of the sample population for which serum samples were available (n =
      120), coproprevalence by APCT was 33.3% (range 27-53.8%) and seroprevalence was
      47.5% (range 29.7-57.9%) by modified unit-based ELISA and 34.2% (range 21.6
      42.1%) by conventional optical density (OD)-based ELISA. Taking APCT as the
      reference method for diagnosis of strongyloidiasis, the sensitivity and
      specificity of the OD-based ELISA were 65% and 81.3%, respectively, and of the
      unit-based ELISA were 77.5% and 71.3%, respectively. Our results indicate that S.
      stercoralis is the predominant parasite in rural north-east Thailand, and that
      APCT and ELISA should be used as complementary diagnostic methods for community
      based parasite surveys, at least among those in high-risk groups.

PMID- 15259467
TI  - The operation, quality and costs of a district hospital laboratory service in
      Malawi.
AB  - Laboratory services are run down in many low-income countries, severely
      constraining their input to patient care and disease surveillance. There are few
      data about the quality and cost of individual components of the laboratory
      service in poorer countries, yet this information is essential if optimal use is
      to be made of scarce resources. Staff time, range of tests, workload, and safety
      procedures were monitored over 12 months (1997-98) in a typical district hospital
      laboratory in Malawi. Data were collected to calculate the total economic cost of
      these services. Of the 31203 tests performed, 84% were to support blood
      transfusion and diagnosis of malaria and tuberculosis (TB). Test quality was
      reasonable for malaria and TB microscopy and blood transfusion, but poor for
      haemoglobin estimation. The cost per test ranged from US dollars 0.35 for
      haemoglobin to US dollars 11.7 per unit of blood issued and the total annual cost
      of the laboratory service was US dollars 32618. Blood transfusion and microscopy
      for malaria and TB comprised the majority of tests. Ensuring that these tests are
      of the highest quality will therefore have the most impact in reducing wastage of
      laboratory resources. Inadequate quality of haemoglobin estimations is a
      particular problem. The findings of this study are likely to be relevant to other
      low-income countries with similar disease burdens.

PMID- 15259468
TI  - Skewing of cytokine profiles towards T helper cell type 2 response in visceral
      leishmaniasis patients unresponsive to sodium antimony gluconate.
AB  - Thirty-two parasitologically confirmed visceral leishmanisis (VL) patients and 23
      healthy, age- and gender-matched controls were recruited between April 2001 and
      March 2002 and studied for intracellular cytokine production after stimulation in
      vitro using a Fluorescence Activated Cell Sorter-based intracellular cytokine
      assay. The VL patients were given i.m. sodium antimony gluconate at a dose of 20
      mg/kg bodyweight daily for 28 d and were grouped as responders (n = 11) or non
      responders (no response after 28 d of treatment; n = 21). Clinically, the non
      responders had longer duration of illness (P < 0.05), larger spleen size (P <
      0.05), and higher parasite load (P < 0.05) than responders. The percentage of T
      helper (Th) cells producing interferon-gamma (IFN-gamma) was significantly higher
      (P < 0.001) in responders than non-responders. Non-responders had higher IFN
      gamma production than control subjects (P < 0.001). The percentage of Th cells
      producing interleukin-4 (IL-4) was significantly higher in non-responders than
      responders (P = 0.003) as well as in healthy subjects (P < 0.001). The frequency
      of IL-4 producing cells in responders and control subjects was similar (P= 0.65).
      The cytokine polarization index, as calculated by the formula loge IFN-gamma
      producing cells/loge IL-4 producing cells, was significantly lower in non
      responders compared with both responders and control subjects (P = 0.003 and P <
      0.001, respectively). The overall cytokine bias in non-responders was skewed
      towards a IL-4 dominance or Th2-like response and this was primarily due to
      induction of IL-4.

PMID- 15259469
TI  - Case reports: intra-aural tick infestations in humans in Sri Lanka.
AB  - Intra-aural tick infestation was detected in 29 patients presenting with acute
      ear pain in the central province of Sri Lanka during June 1999 to January 2002.
      The ages ranged from 9 months to 67 years. All showed oedematous aural canals and
      enlarged adjacent lymph nodes. Of 30 ticks removed, 29 were nymphs of Dermacentor
      auratus and 1 and male Hyalomma marginatum isaaci.

PMID- 15259470
TI  - Case reports: acute hookworm infection: an unusual cause of profuse watery
      diarrhoea in returned travellers.
AB  - We describe 3 returned travellers who developed profuse watery diarrhoea
      associated with marked blood eosinophilia. Delayed appearance of ova in stool
      samples caused difficulty in establishing diagnoses of acute hookworm infection.
      Low activity of ivermectin against hookworm resulted in failure of empiric
      treatment with this agent prior to parasitological diagnosis.

PMID- 15259471
TI  - Neurocysticercosis in children: clinical findings and response to albendazole
      therapy in a randomized, double-blind, placebo-controlled trial in newly
      diagnosed cases.
AB  - The clinical findings of neurocysticercosis, diagnosed primarily on the basis of
      computed tomography (CT), and response to albendazole therapy in a randomized,
      double-blind, placebo-controlled trial were studied in 72 newly diagnosed
      children aged 1.5-12 years admitted to hospital in New Delhi, India, during March
      to July 2000. The lesions by initial CT were mostly single with perilesional
      oedema, and were located in the parietal lobes. The most common clinical finding
      was partial seizure (79.2%). The outcome of the albendazole trial was assessed
      through changes in CT lesions and status of seizure after 6 months of follow-up;
      about 55% of the lesions had disappeared and about 80% of the children were
      seizure-free. The frequency of healing of CT lesions in the albendazole-treated
      group and placebo group was 54.2% and 55.2%, respectively, and the frequency of a
      seizure-free state in the albendazole-treated group and placebo group was 87.5%
      and 77.5%, respectively; the differences were not statistically significant.
      Changes in lesions by CT and the recurrence of seizures after 6 months of follow
      up were not related to the number of lesions by initial CT and albendazole was
      not beneficial in neurocysticercosis in children with ring-enhancing lesions in
      CT.

PMID- 15259472
TI  - Age, temperature, and parasitaemia predict chloroquine treatment failure and
      anaemia in children with uncomplicated Plasmodium falciparum malaria.
AB  - The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been
      increasing in sub-Saharan Africa and parts of South America over the last 2
      decades, and has been associated with increased anaemia-associated morbidity and
      higher mortality rates. Prospectively collected clinical and parasitological data
      from a multicentre study of 788 children aged 6-59 months with uncomplicated P.
      falciparum malaria were analysed in order to identify risk factors for
      chloroquine treatment failure and to assess its impact on anaemia after therapy.
      The proportion of chloroquine treatment failures (combined early and late
      treatment failures) was higher in the central-eastern African countries
      (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%).
      Using logistic regression, predictors of early treatment failure included younger
      age, higher baseline temperature, and greater levels of parasitaemia. We conclude
      that younger age, higher initial temperature, and higher baseline parasitaemia
      predict early treatment failure and a higher probability of worsening anaemia
      between admission and days 7 or 14 post-treatment.

PMID- 15259473
TI  - No benefits from combining chloroquine with artesunate for three days for
      treatment of Plasmodium falciparum in Guinea-Bissau.
AB  - The use of a combination of chloroquine and artesunate has been suggested for
      treatment of malaria in Africa. We used concomitant as well as sequential
      medication with these 2 drugs in relation to each drug separately for children
      infected with Plasmodium falciparum in Guinea-Bissau from March 2000 to November
      2001. By block-randomization, 474 children with symptomatic malaria were divided
      into 4 groups and given either a total of 8 mg artesunate per kg bodyweight for 3
      d, a total of 25 mg chloroquine base per kg bodyweight for 3 d, both drugs
      concomitantly for 3 d, or both drugs in sequence. All children were followed
      weekly for 5 weeks. On day 28, parasites had been detected in 40% of the children
      who were treated with artesunate only compared with 21% treated with chloroquine,
      20% treated with artesunate in combination with chloroquine, and 16% treated with
      artesunate and chloroquine in sequence; on day 35 the corresponding percentages
      were 48%, 29%, 27%, and 24%, respectively. The outcome of the combination of
      chloroquine and artesunate in the doses studied was similar to the outcome of
      chloroquine monotherapy regardless of whether the 2 drugs are given concomitantly
      (relative risk [RR] = 0.93, 95% CI 0.56-1.53, P = 0.76) or in sequence (RR =
      0.78, 95% CI 0.47-1.28, P = 0.32). Thus, neither an antagonistic, an additive, or
      a synergistic effect of the 2 drugs was indicated.

PMID- 15259474
TI  - Case report: combination artemether-lumefantrine and haemolytic anaemia following
      a malarial attack.
AB  - A case of a patient who was admitted to hospital in Paris, France, in February
      2001 with autoimmune haemolytic anaemia, probably due to artemether-lumefantrine
      therapy, is presented. Such a complication has previously been observed in
      patients receiving drugs containing aryl-amino-alcohols but never before in a
      patient receiving lumefantrine and may be associated with the increase in
      episodes of blackwater fever seen in recent years.

PMID- 15259475
TI  - Monitoring of Plasmodium vivax sensitivity to chloroquine in vitro in Thailand.
AB  - The sensitivity of Plasmodium vivax to chloroquine in vitro was investigated in
      patients admitted to the Bangkok Hospital for Tropical Diseases, Thailand,
      between September 2001 and May 2002. Of 42 isolates, 34 were successfully tested
      for parasite sensitivity to chloroquine in vitro; the results showed a
      significant decrease in sensitivity compared with data published in 1989 and
      1995: the IC50 and IC90 were 187.2 and 1217.9 ng/mL blood, respectively, an
      approximate 4-fold decrease in sensitivity in comparison with other data from the
      past 2 decades. A number of in vitro tests were performed simultaneously using
      both WHO microplates and our own laboratory-prepared pre-dosed microplates under
      the same conditions and there was no significant difference between the results.

PMID- 15259476
TI  - Efficacy of a 14-day primaquine regimen in preventing relapses in patients with
      Plasmodium vivax malaria in Mumbai, India.
AB  - We studied the antirelapse efficacy of a supervised 14-d 15 mg/d regimen of
      primaquine therapy (n = 131) compared with no antirelapse therapy (n = 142) in
      273 patients with confirmed Plasmodium vivax malaria in Mumbai, India, between
      July 1998 and April 2000. There were 6/131 (4.6%) recurrences in patients given
      primaquine compared with 13/142 (9.2%) in those not given antirelapse therapy. In
      the 14-d primaquine group, polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) genotyping analysis of pre- and post-treatment blood
      samples was done for the 6 patients who had a recurrence of parasitaemia and the
      results gave a true relapse rate of 2.29% (3/131), 2 samples were classified as
      reinfections and 1 sample did not amplify. Our results indicate probable
      resistance to the 14-d regimen of primaquine for the first time in India and
      illustrate the need to (i) monitor patients given this regimen and (ii) carry out
      comparative studies between primaquine and new drugs such as tafenoquine and
      bulaquine for preventing relapses.

PMID- 15259477
TI  - Effectiveness of primaquine terminal prophylaxis against late primary attacks of
      Plasmodium vivax malaria: a case-control study among troops of the Republic of
      Korea army.
AB  - Plasmodium vivax malaria is an important cause of morbidity among troops
      operating in endemic areas near the Demilitarized Zone in the Republic of Korea
      (ROK). The ROK Army has been administering antimalarial chemoprophylaxis to those
      troops at greatest risk of malaria since 1997. The number of recipients increased
      from 15000 in 1997 to 90000 in 2001. We undertook a case-control study to
      estimate the effectiveness of primaquine prophylaxis against late primary attacks
      of P. vivax malaria in ROK Army troops. Microscopically confirmed cases of P.
      vivax malaria were identified through hospital-based surveillance. Controls were
      matched by unit. Between 1 November 2001 and 31 May 2002, 68 cases and 137
      matched controls with confirmed chemoprophylaxis status were enrolled. The
      estimated effectiveness of primaquine prophylaxis was 32% (95% CI 23-63%). Our
      results suggest that the effectiveness of primaquine prophylaxis against late
      primary attacks of P. vivax malaria may be insufficient for soldiers of the ROK
      Army.

PMID- 15259478
TI  - New World cutaneous leishmaniasis in returned travellers: treatment failures
      using intravenous sodium stibogluconate.
AB  - Treatment outcome was determined among a cohort of travellers who returned to the
      UK between February 2000 and February 2001 with New World cutaneous leishmaniasis
      caused by species of the Leishmania (Viannia) subgenus. Among 18 patients who
      completed treatment with 20 mg/kg/d of i.v. sodium stibogluconate (NaSb) for 20
      d, early relapse of disease occurred in 2 patients with regional dissemination in
      1 and mucocutaneous involvement in the other. Drug susceptibility testing in
      vitro of the clinical isolate from 1 of these patients confirmed tolerance to
      high concentrations of NaSb.

PMID- 15259479
TI  - Long-lasting reduction of Brugia timori microfilariae following a single dose of
      diethylcarbamazine combined with albendazole.
AB  - The long-term effect of a single oral dose of 6 mg/kg bodyweight of
      diethylcarbamazine (DEC) combined with 400 mg albendazole (ALB) on the
      microfilariae (mf) of the lymphatic filarial parasite Brugia timori was studied
      on Alor island, Indonesia from April 2001 to April 2002. Before treatment the
      geometric mean of the mf density in 96 infected study subjects was 150 mf/mL
      night blood (range 1-5696 mf/mL). One year after treatment 69 subjects (72%) were
      mf-negative and the overall geometric mean mf density reduced to 3 mf/mL (0-2456
      mf/mL). The reduction of mf was more pronounced 1 year after treatment compared
      with 6 months after treatment. It can be concluded that a single dose of DEC +
      ALB leads to a long-term and progressive suppression of B. timori mf for at least
      1 year. Therefore, DEC+ ALB can be recommended as an effective strategy to
      control B. timori infection in the framework of the Global Programme to Eliminate
      Lymphatic Filariasis.

PMID- 15259480
TI  - Schistosomiasis prophylaxis in vivo using N,N-diethyl-m-toluamide (DEET).
AB  - Topical N,N-Diethyl-m-toluamide (DEET) was studied as a schistosomiasis
      prophylactic in vivo for the use of individuals with limited exposure. Fifteen
      subjects, on a 3-week expedition to Lake Malawi in September 2001, applied 50%
      DEET to their skin after exposure to lake water. No subjects developed evidence
      of a new infection at 3-month follow-up.

PMID- 15259481
TI  - Comparison of two single-day regimens of triclabendazole for the treatment of
      human pulmonary paragonimiasis.
AB  - A well-tolerated single-day treatment regimen is required for the community-based
      treatment of pulmonary paragonimiasis. To identify an optimal single-day
      treatment regimen, an open clinical trial was performed to compare the efficacy
      of 2 single-day regimens of triclabendazole. From 1991 to 1993, a total of 154
      Ecuadorian patients were allocated to receive either a single dose or 2 doses of
      10 mg/kg triclabendazole. Treatment with both regimens was associated with a
      rapid parasitological response (determined by clearance of Paragonimus eggs from
      sputum), resolution of most clinical symptoms and radiological signs, and only
      mild adverse effects. At 3 months after treatment, the cure rate (clearance of
      eggs from sputum) was 90.9% in the 2-dose group and 84.4% in the single-dose
      group. Re-treatment with a second 2-dose regimen was curative in all remaining
      patients by 1 year of follow-up. Our findings show that both single-day treatment
      regimens of triclabendazole were highly effective in the treatment of pulmonary
      paragonimiasis and suggest that patients should be re-examined at 3 months to
      determine the need for repeat treatment.

PMID- 15259482
TI  - Temporal variations in immune responses to conserved regions of Plasmodium
      falciparum merozoite surface proteins related to the severity of a prior malaria
      episode in Gabonese children.
AB  - We measured cellular and humoral responses to conserved regions of Plasmodium
      falciparum merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) at different
      times during and after acute infection in matched groups of Gabonese children who
      presented with either mild or severe malaria. We used an MSP-1(19) recombinant
      protein and peptides corresponding to conserved epitopes in MSP-1 and MSP-2 N-
      and C-terminal regions. The prevalences of peptide-induced cell-mediated
      responses were maximal in both groups when they were healthy, but were
      consistently higher in the mild malaria group, whereas peptide-specific antibody
      responses were consistently highest in the severe malaria group. Recombinant MSP
      1(19) protein-specific antibody levels in the 2 groups were similar both prior to
      and 1 month post-treatment but declined later when the children were healthy and
      parasite-free, to a significantly lower level in those admitted with severe
      malaria, reflecting the profile of the predominant MSP-1(19)-specific
      immunoglobulin G1 isotype. This finding implies a defect in the ability of
      children with a history of severe malaria to maintain an antibody response
      putatively associated with immunity to P. falciparum malaria.

PMID- 15259483
TI  - Antileishmanial antibodies in an outbreak of visceral leishmaniasis in eastern
      Sudan: high antibody responses occur in resistant subjects and are not predictive
      of disease.
AB  - A 3-year longitudinal survey was carried out from 1998 to 2000 in a village in
      eastern Sudan where a visceral leishmaniasis (VL) outbreak occurred. Leishmania
      specific antibodies were analysed by enzyme-linked immunosorbent assay and
      immunoblotting. Immunoblot analysis detected antibodies to Leishmania in 80% of
      the healthy subjects and half of them harboured high immunoglobulin (Ig) G
      antibody levels, similar to those of VL patients. These antibodies belonged to
      the IgG1 and IgG3 subclasses but neither their respective levels nor the
      immunoblot recognition patterns were predictive of VL. During this epidemic, a
      large proportion of subjects had a high antileishmanial antibody response,
      indicating that they were infected by Leishmania though most of them remained
      healthy during the whole study period. These results obtained in the context of
      an outbreak contrast with those obtained from studies performed in endemic areas
      characterized by lower parasite transmission levels. Furthermore, the clinical
      and serological follow-up of our study subjects showed that VL occurred mainly in
      subjects who had been serologically positive for 5-24 months rather than
      resulting from primo infection by the parasite.

PMID- 15259484
TI  - Immunotherapy of american cutaneous leishmaniasis in Venezuela during the period
      1990-99.
AB  - Of a total of 11532 Venezuelan patients with American cutaneous leishmaniasis
      (ACL) receiving immunotherapy with a combined vaccine containing heat-killed
      Leishmania promastigotes and bacille Calmette-Guerin (BCG) during the period 1990
      99, we evaluated 5341 from 4 widely separated geographical states. Clinical
      healing varied from 91.2 to 98.7%, with an average of 95.7%. Adverse reactions
      were mild and limited to those associated with BCG vaccination alone.
      Immunotherapy failures in 143 patients included 54.5% with typical localized
      ulcers and 45.5% with non-mucosal intermediate cutaneous leishmaniasis (ICL).
      Less than 2% of the patients in this study had lesions suggestive of ICL. The
      disproportionately large number of immunotherapy failures in the ICL group
      suggests that it should not be used as monotherapy in this group. Weaker
      reactivity to purified protein derivative in immunotherapy failures, while not
      statistically significant in the small group reported here, suggests the
      possibility that these patients develop a relatively torpid immune response. The
      high percentage of clinical cures achieved with immunotherapy, associated with
      few secondary effects and low cost, support the use of immunotherapy in the
      routine treatment of localized ACL.

PMID- 15259485
TI  - Relationship between bacille Calmette-Guerin vaccination, Mantoux test
      positivity, and geohelminth infection.
AB  - To investigate the potential protective effects of Bacille Calmette-Guerin (BCG)
      vaccination scar and sensitization to tuberculin against geohelminth infections,
      we conducted a cross-sectional study among school age children in rural
      communities in Pichincha Province in Ecuador where BCG vaccination is routinely
      given at birth. A total of 944 children aged 8-14 years were evaluated for the
      presence of BCG scars and sensitization to tuberculin, and underwent faecal
      examination for geohelminth parasites. BCG scars were present in 88.2% of
      children and positive Mantoux tests were observed in 19.1% of children.
      Geohelminth prevalence was high with 70.3% infected with any parasite, 52.1% with
      Ascaris lumbricoides, 52.3% with Trichuris trichiura, 7.6% with Ancylostoma
      duodenale, and 3.0% with Strongyloides stercoralis. In multivariate analyses, the
      presence of BCG vaccine scars was not significantly associated with infections
      with any geohelminth parasite (adjusted odds ratio [AOR] = 0.74, 95% CI 0.43
      1.28, P = 0.28), but an inverse association was observed for infections with S.
      stercoralis that was of borderline statistical significance (AOR = 0.38, 95% CI
      0.15-1.00, P = 0.05). There were no associations between sensitization to
      tuberculin and infection with geohelminth parasites. The data provide little
      support for an important protective role of neonatal BCG vaccination or current
      mycobacterial sensitization against geohelminth infections.

PMID- 15259486
TI  - Eosinophilia and progression to active tuberculosis in HIV-1-infected Ugandans.
AB  - It has been suggested that type 1 immune responses protect against tuberculosis
      (TB), while type 2 responses, such as those induced by helminths, may suppress
      protective responses and increase susceptibility to TB. Factors associated with
      progression to active TB were investigated in a cohort of HIV-1-infected Ugandan
      adults, a group at high risk of TB. High rates of subsequent progression to
      active TB were associated with eosinophil counts > or = 0.4 x 10(9)/L at
      enrolment. Eosinophilia at enrolment was associated with male gender, low socio
      economic status, high CD4+ T cell counts, and schistosomiasis, but adjusting for
      these factors did not explain the association of eosinophilia with progression to
      active TB (adjusted rate ratio = 2.76, P = 0.004). Eosinophilia is most likely to
      be indicative of a type 2 immune response induced by helminth infection in this
      Ugandan cohort, but the mechanism of the observed association between
      eosinophilia and risk of TB remains to be determined.

PMID- 15259487
TI  - Evaluation of the upper esophageal sphincter (UES) using simultaneous high
      resolution endoluminal sonography (HRES) and manometry.
AB  - The aim of this study was to characterize the motion, morphology, and pressure of
      the upper esophageal sphincter (UES). The UES and its surrounding structures were
      evaluated in seven normal subjects and four human cadavers, using simultaneous
      high-resolution endoluminal sonography and manometry. The UES musculature on
      ultrasound is a C-shaped structure with an angle of 107 +/- 19 degrees. The mean
      peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA)
      of 0.87 +/- 0.33 cm2. During swallowing, the UES moved in an orad direction.
      Localizing the UES sonographically, the peak UES pressure in the cadavers was
      19.7 +/- 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than
      the upper esophageal body. In the cadaver studies, the UES was imaged in
      conjunction with a significant increase in pressure, indicating that the pressure
      is due to passive mechanical conformational changes.

PMID- 15259488
TI  - Effect of phasic contractions and tone of the proximal stomach on triggering of
      transient lower esophageal sphincter relaxation.
AB  - We hypothesized that transient lower esophageal sphincter relaxation (TLESR) is
      triggered by a discrete motor event, i.e., a phasic contraction or a tonic change
      of the proximal stomach. The combined esophageal manometry-gastric barostat
      tracings obtained from 11 healthy subjects during 2-hr continuous isobaric
      gastric distension were reviewed. Volume waves, i.e., phasic contractions, were
      analyzed in the 1 and 5 min before onset of each TLESR and in corresponding
      control periods. Intrabag volume, i.e., proximal gastric tone, was also measured
      in the 5-min periods. The number of volume waves was similar in the 1- and 5-min
      pre-TLESR and control periods (0 [0-1], median [IQ range], vs 0 [0-1] and 4 [0.8
      5] vs 3 [2-4], respectively], and so were their amplitude, duration, and
      frequency distribution. Five-minute intrabag volume was also similar (529 +/- 77
      [mean +/- SE] vs 532 +/- 74 ml). Our observations suggest that TLESR is not
      triggered by a preceding phasic contraction or by a different tone of the
      proximal stomach.

PMID- 15259489
TI  - Electrogastrography differentiates reflux disease with or without dyspeptic
      symptoms.
AB  - Many patients with gastroesophgeal reflux disease (GERD) may also have
      overlapping symptoms of dyspepsia. This study was to examine if GERD patients
      could be separated into meaningful groups based on their gastric myoelectrical
      characteristics. The study included 20 GERD patients with dyspeptc symptoms
      (GERD+) and 17 patients with GERD. Gastric myoelectrical activity was assessed
      using cutaneous electrodes to record electrogastrograms (EGGs). The GERD+
      patients ingested smaller volumes of water compared to patients with GERD (P <
      0.05). At baseline, the percentage of gastric myoelectrical power in the normal 3
      cpm range was significantly less in patients with GERD+ compared with the GERD
      subjects (P = 0.01). Power in the bradygastria range was significantly greater in
      patients with GERD+ (P = 0.005). The GERD+ group had a significant increase in
      the percentage of power in the tachygastria range later after ingesting the water
      load (P < 0.01). In conclusion, this study has shown that more gastric
      dysrhythmias were detected in the GERD+ patients accompanied with altered
      perception of stomach fullness.

PMID- 15259490
TI  - Effects of intestinal electrical stimulation on intestinal dysrhythmia and
      symptoms in dogs.
AB  - The aim of this study was to investigate the effect of intestinal electrical
      stimulation on small intestinal dysrhythmia and motion sickness-like symptoms
      induced by vasopressin. Female dogs chronically implanted with two pairs of
      electrodes on jejunum serosa were used in a four-session study. Saline and
      vasopressin were infused in sessions 1 and 2, respectively. Sessions 3 and 4 were
      the same as session 2, except a long- or short-pulse intestinal electrical
      stimulation was applied on the proximal pair of electrodes. Intestinal slow waves
      and motion sickness-like symptoms were recorded in each session. Results were as
      follows. (1) Vasopressin induced intestinal dysrhythmia, uncoupling of slow
      waves, and vomiting and motion sickness-like symptoms (P < 0.05, ANOVA). (2)
      Intestinal electrical stimulation with long pulses, but not short pulses, was
      capable of preventing vasopressin-induced intestinal dysrhythmia. (3) Intestinal
      electrical stimulation with short pulses, but not long pulses, prevented vomiting
      and the motion sickness-like symptoms. It is concluded that vasopressin induces
      intestinal dysrhythmia. Long-pulse intestinal stimulation normalizes vasopressin
      induced intestinal slow-wave abnormalities with no improvement in symptoms. Short
      pulse stimulation prevents emetic symptoms induced by vasopressin but has no
      effect on slow waves. These data suggest different mechanisms involved with
      different methods of intestinal stimulation.

PMID- 15259491
TI  - Vagal afferent is involved in short-pulse gastric electrical stimulation in rats.
AB  - This study investigated the effect of gastric electrical stimulation (GES) on
      vagal activity and its possible vagal afferent-mediated mechanisms. Sixty rats
      implanted with gastric serosal electrodes were divided into six groups (control,
      vehicle, local capsaicin, perivagal capsaicin, systemic capsaicin, and vagotomy).
      GES with six sets of parameters was performed in the control group; and GES with
      one set of effective parameters was performed in the other five groups. Spectral
      analysis of heart rate variability was used to assess vagal activity. Regular
      gastric slow waves were recorded in the control rats with a frequency of 4.8
      cycles/min. Vagotomy significantly reduced the frequency of the gastric slow wave
      but did not induce dysrhythmia. Capsaicin did not alter the gastric slow wave.
      Short-pulse (300-microsec) GES significantly increased vagal activity at a
      frequency four times the intrinsic slow-wave frequency. Stimulation at a lower
      frequency or with a long pulse (300 msec) had no effect on vagal activity.
      Vagotomy or capsaicin administered perivagally, systemically, or locally
      abolished the effect of GES on the vagal activity. GES with short but not long
      pulses is capable of altering vagal activity. This effect is mediated by
      capsaicin-sensitive vagal afferent fibers.

PMID- 15259492
TI  - Loss of sympathetic coordination appears to delay gastrointestinal transit in
      patients with spinal cord injury.
AB  - Patients with spinal cord injury (SCI) often suffer from many gastrointestinal
      (GI) complaints, while delayed GI transit exists in these patients. We are
      interested in whether the lost sympathetic activity is one of the mechanisms
      leading to disturbed GI transit in these subjects. Using a noninvasive hydrogen
      breath test representing orocecal transit time (OCTT) to study GI transit, 36 SCI
      patients and 12 age- and sex-matched healthy volunteers were enrolled in our
      study. Meanwhile, electrocardiogram was performed for all subjects. Finally,
      spectral analysis of heart rate variability (HRV) was then obtained to assess
      their sympathovagal balance. SCI patients had higher occurrences of GI symptoms,
      e.g., nausea/vomiting, belching/hiccup, and constipation, compared to controls (P
      < 0.05). OCTT was delayed in SCI patients compared to controls (180.8 +/- 10.7 vs
      98.3 +/- 14.4 min; P < 0.001). The OCTTs of SCI patients were negatively
      correlated with their low frequencies of HRV (r = -0.384, P = 0.021). In
      addition, OCTT was further delayed in quadriplegic patients than paraplegic
      patients (195.8 +/- 14.5 vs 143.6 +/- 19.4 min; P = 0.031). However, neither the
      SCI etiology, the injury duration, nor the high frequency of HRV had any
      influence on the delayed OCTT in SCI patients. We conclude that the GI transit of
      SCI patients is delayed. This transit disturbance is probably due to loss of
      sympathetic activity, which is one of the essential components in the
      coordination of GI peristalsis.

PMID- 15259493
TI  - Impaired gastric myoelectrical activity in patients with Parkinson's disease and
      effect of levodopa treatment.
AB  - The aim of this study was to evaluate gastric myoelectrical activity in patients
      with Parkinson's disease during and after levodopa treatment. Thirteen
      Parkinson's patients and 13 age-matched Parkinson's-free controls were enrolled.
      Electrogastrography was used to record gastric myoelectrical activity in all
      subjects for 30 min before and 30 min after a standard meal. In the group with
      Parkinson's disease, gastric myoelectrical activity was recorded during both the
      "on" (with levodopa treatment) and the "wearing-off" (without levodopa for at
      least 12 hr) periods. Results were as follows. (1) The patients without treatment
      showed a significantly lower percentage of regular slow waves and a significantly
      higher instability coefficient of the dominant frequency; (2) the patients showed
      an absence of the normal postprandial increase in gastric slow wave frequency
      which was seen in the controls: and (3) treatment with levodopa resulted in an
      improvement in the fed state, including a marginal increase in the percentage of
      regular slow waves (P = 0.1), a significant decrease in the instability
      coefficient, and an enhanced postprandial power increase. In conclusion, patients
      with Parkinson's disease have reduced slow wave rhythmicity and an impaired
      postprandial response in gastric myoelectrical activity. These abnormalities may
      be partially corrected with levodopa treatment in the fed state.

PMID- 15259494
TI  - Diminished retention of food in the proximal stomach correlates with increased
      acidic reflux in patients with gastroesophageal reflux disease and dyspeptic
      symptoms.
AB  - This work aimed at evaluating the intragastric distribution of food in patients
      with GERD and dyspepsia and its relationship to acidic reflux episodes. Gastric
      emptying and food retention in the proximal stomach were evaluated by
      scintigraphy in 12 healthy subjects and 19 patients with GERD and dyspepsia after
      a liquid test meal. Patients also underwent 24-hr esophageal pH monitoring, which
      included a 2-hr postprandial period following a similar test meal. Total gastric
      emptying was similar in patients and controls, whereas proximal gastric retention
      (AUCprox/AUCtot) was significantly decreased in patients (mean +/- SD: 0.48 +/-
      0.07 vs. 0.56 +/- 0.06; P = 0.02). Within the GERD-dyspepsia group, a significant
      negative correlation was found between proximal gastric retention and the number
      of acidic reflux episodes. We concluded that abnormally decreased retention of
      gastric contents in the proximal stomach after a liquid meal may contribute to
      the pathogenesis of acidic reflux episodes in patients with GERD and dyspepsia.

PMID- 15259495
TI  - Gastric emptying and gastrointestinal transit of liquid in awake rats is delayed
      after acute myocardial infarction.
AB  - The outcome of acute myocardial infarction (AMI) on gastrointestinal motor
      behavior was assessed in awake rats. Under anesthesia, they were submitted to
      thoracotomy followed or not by occlusion of the left coronary artery. Next day,
      they were gavage fed (1.5 ml) with phenol red in 5% glucose solution and
      sacrificed 10, 20, or 30 min later. Each subset consisted of 7 to 19 animals. Dye
      recovery in the stomach, proximal, mid, and distal small intestine was obtained
      by spectrophotometry. Infarcted left ventricle plus septum area was about 48.9 +/
      2.8, 55.1 +/- 6.7, and 54.1 +/- 8.1% (respectively, for 10-, 20-, and 30-min
      subsets). AMI increased gastric dye retention by 25.5, 51.3, and 65.1%
      (respectively, for 10-, 20-, and 30-min subsets), while it decreased mid small
      intestine retention at 30 min (45.3%) as well as distal retention at 10 min
      (90.5%) and 20 min (90%). A positive correlation (rS = 0.64) was found between
      infarcted area and gastric retention values at 10 min. AMI also increased (P <
      0.05) central venous pressure values in all subsets (3.8 +/- 0.2 vs. -2.1 +/-
      1.5, 1.4 +/- 0.1 vs. 0.5 +/- 0.2, and 1.6 +/- 0.4 vs. -0.2 +/- 0.3 cm H2O), while
      it decreased (P < 0.05) mean arterial pressure (95.0 +/- 2.6 vs. 110.0 +/- 3.9
      and 106.0 +/- 2.0 vs. 113.0 +/- 3.0 mm Hg, respectively, at 10 and 30 min), and
      increased (P < 0.05) the 10-min heart rate values (429.6 +/- 11.3 vs. 374.0 +/-
      19.8 bpm). Omeprazole pretreatment did not alter this phenomenon. In another
      group of rats, cardiac chemoreflex stimulation by i.v. phenylbiguanide increased
      gastric dye retention by 51.1%. In conclusion, AMI delays the gastric emptying
      and gastrointestinal transit of liquid in awake rats.

PMID- 15259496
TI  - Chronic visceral hypersensitivity renders defecation more susceptible to stress
      via a serotonergic pathway in rats.
AB  - Visceral hypersensitivity, intestinal dysmotility, and stress play major roles in
      irritable bowel syndrome. However, the significance of visceral hypersensitivity
      in stress-induced changes of colorectal motor function is not conclusive. A rat
      model of chronic visceral hypersensitivity was induced by mechanical colorectal
      irritation during postnatal development. Defecation and colonic transit time were
      not different between the visceral hypersensitivity and the control groups at
      baseline. Stress and a 5-hydroxytryptamine (5-HT) agonist both resulted in a
      significant increase in defecation in the visceral hypersensitivity group
      compared with the controls. Prior administration of granisetron, a 5-HT3 receptor
      antagonist, inhibited stress-induced changes in defecation in the visceral
      hypersensitivity group as well as the controls. Stress-induced acceleration of
      colonic transit was not significantly different between the two groups. Our
      results indicate that chronic visceral hypersensitivity can modulate the effect
      of stress on defecation via a serotonergic pathway and suggest that visceral
      hypersensitivity may be related to the susceptibility of the defecative response
      to stressful events in patients with irritable bowel syndrome.

PMID- 15259497
TI  - Schatzki ring and Barrett's esophagus: do they occur together?
AB  - Our purpose was to determine the prevalence of Barrett's esophagus in the
      presence of Schatzki ring. We performed a retrospective case-control study with
      an endoscopic database. Barrett's esophagus was present in 3 of 409 (0.73%)
      patients with Schatzki ring and in 16 of 888 (1.80%) patients without Schatzki
      ring. Short segment Barrett's esophagus was present in 3 cases and 10 controls.
      Long segment Barrett's esophagus was present in no cases and six controls.
      Logistic regression models adjusting for the presence of a hiatal hernia revealed
      a significant decrease in the odds of Barrett's esophagus in cases compared to
      controls (OR, 0.24; 95% CI, 0.07-0.87; P = 0.029). Barrett's esophagus is less
      prevalent in patients with Schatzki ring compared to patients without Schatzki
      ring. Long segment Barrett's esophagus was not observed in patients with Schatzki
      ring. A responsible protective effect or mutually exclusive pathophysiology
      should be considered.

PMID- 15259498
TI  - Herpes simplex virus type 1 esophagitis in an immunocompetent adolescent.

PMID- 15259499
TI  - Helicobacter pylori down-regulates the receptors of vascular endothelial growth
      factor and angiopoietin in vascular endothelial cells: implications in the
      impairment of gastric ulcer healing.
AB  - Once a peptic ulcer has developed, angiogenesis plays a critical role in its
      healing by enhancing the microcirculation in the healing site. Previous reports
      have shown that Helicobacter pylori infection delays the healing of chronic
      gastric ulcers. To elucidate the mechanism of delayed ulcer healing caused by H.
      pylori, we investigated the angiogenic phenotype and expression of receptors of
      angiogenic growth factors in vascular endothelial cells. After human umbilical
      vein endothelial cells (HUVECs) were treated with H. pylori water extract,
      angiogenic phenotype was determined by capillary tube formation and DNA synthesis
      assay. The expressions of the receptors of vascular endothelial growth factor and
      angiopoietin-1/-2 were assessed by reverse transcription-polymerase chain
      reaction and Western blot analysis in HUVECs and by double immunofluorescent
      staining in gastric mucosa. Angiogenic signaling in HUVECs was evaluated by using
      a quantitative intracellular calcium mobilization assay. H. pylori water extract
      significantly inhibited capillary tube formation and DNA synthesis and down
      regulated the expressions of receptors of vascular endothelial growth factor and
      angiopoietin in HUVECs. H. pylori water extract suppressed vascular endothelial
      growth factor-induced intracellular calcium signaling in HUVECs. H. pylori may
      inhibit the expression of angiogenic growth factor receptors in vascular
      endothelial cells, which could explain, in part, the delayed healing of gastric
      ulcer by H. pylori.

PMID- 15259500
TI  - Gastric acid normosecretion is not essential in the pathogenesis of mild erosive
      gastroesophageal reflux disease in relation to Helicobacter pylori status.
AB  - In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is
      considered to be one of the most important factors, but little is known about the
      degree of gastric acid secretion in GERD patients. In this study, we evaluated it
      in GERD patients and control subjects by 24-h intragastric pH, and serological
      and histological investigations, in relation to Helicobacter pylori (H. pylori)
      status. In H. pylori-negative GERD patients gastric acid secretion was similar to
      that in H. pylori-negative control subjects. In H. pylori-positive GERD patients,
      in particular, mild GERD patients, it decreased significantly compared to that in
      H. pylori-negative control subjects, but the degree of decrease was smaller than
      in H. pylori-positive control subjects. Results of serological and histological
      evaluation were supportive. In conclusion, in some GERD patients, gastric acid
      secretion was significantly decreased. Increased or maintained gastric acid
      secretion was not essential in the pathogenesis of mild GERD.

PMID- 15259502
TI  - Effect of steroid therapy for late dumping syndrome after total gastrectomy:
      report of a case.

PMID- 15259501
TI  - Serum pepsinogens as a predicator of the topography of intestinal metaplasia in
      patients with atrophic gastritis.
AB  - The importance of atrophic gastritis with intestinal metaplasia is related to the
      fact that it increases the risk of gastric cancer development. The aim of this
      study is to evaluate the diagnostic potential of serum pepsinogens in predicting
      the topography of intestinal metaplasia. Both dye endoscopy and 13C-urea breath
      test were carried out in 878 subjects. Serum pepsinogen I, pepsinogen II, and IgG
      antibody to Helicobacter pylori were measured. The overall prevalence of
      intestinal metaplasia was higher in subjects with lower PG I/II ratios and lower
      PG I values. Based on ROC curves, a cutoff value for pepsinogen I/II ratio of
      less than 3.0 would have identified intestinal metaplasia with a sensitivity of
      71.7% and a specificity of 66.7% in Helicobacter pylori-positive subjects. It is
      possible that serum pepsinogens could be used as a screening test for high-risk
      subjects with intestinal metaplasia.

PMID- 15259504
TI  - Usefulness of gallbladder ejection fraction estimation to predict the recurrence
      of biliary pain in patients with symptomatic gallstones who did not undergo
      cholecystectomy.
AB  - This study was performed to evaluate any predictable factors associated with
      recurrence of biliary pain in symptomatic gallstone patients who did not undergo
      cholecystectomy because of operative risk, advanced age, and/or their refusal.
      The relationships among age, gender, body mass index, frequency of biliary pain
      before diagnosis, period between the last symptom attack and the hospital visit,
      size and number of gallstones, gallbladder ejection fraction (GBEF), compliance
      of ursodeoxycholic acid therapy, and recurrence of biliary pain were examined.
      The recurrence of biliary pain developed in 15 of 31 patients during the median
      29-month follow-up. The cumulative 1-, 2-, and 3-year recurrence rates of biliary
      pain were 22.8, 40.9, and 53.0% and significantly associated with abnormal GBEF
      (hazard ratio, 3.12; 95% CI, 1.10-8.87; P = 0.032). In symptomatic gallstone
      patients with abnormal GBEF, cholecystectomy is strongly advisable because of the
      high risk of repeated pain attacks.

PMID- 15259503
TI  - Chronic alcohol-induced alterations in the pancreatic secretory control
      mechanisms.
AB  - Chronic alcohol ingestion appears to increase susceptibility of the pancreas to
      pancreatitis through multiple mechanisms. The aim of the current study was to
      determine the effect of chronic low- and high-dose alcohol consumption on the
      neurohormonal control of the exocrine pancreas in rats. Male Wistar rats were fed
      Lieber DeCarli liquid control-, low-, and high-dose alcohol diets for 3 months.
      Pancreatic exocrine secretion was measured under basal and 2-deoxy-D-glucose (2
      DG)-, CCK-, bethanechol-, or meal-stimulated conditions while on chronic alcohol
      diets and after 2-DG or CCK stimulation during alcohol withdrawal in awake rats.
      Chronic alcohol ingestion was associated with a dose-related inhibition of basal
      pancreatic protein secretion, which was reversed upon alcohol withdrawal. Low
      dose alcohol feeding had no effect on bethanechol-stimulated pancreatic secretion
      but altered 2-DG-stimulated pancreatic secretion. In chronic high-dose alcohol
      rats, meal- and bethanechol-stimulated protein secretion was significantly
      potentiated during early and late phases. The response to CCK appeared to be
      disinhibited, whereas the response to 2-DG was uniformly blunted. Upon withdrawal
      of low-dose alcohol, the response to 2-DG was potentiated, whereas with the
      withdrawal of high-dose alcohol, the response to CCK was potentiated. Adaptation
      to chronic alcohol consumption differs depending on the alcohol dose. The most
      significant effects were seen after high-dose alcohol withdrawal, with apparent
      loss of central inhibitory regulation combined with exaggerated response at the
      acinar cell level. This combination of factors could increase susceptibility to
      acute alcoholic pancreatitis through a hyperstimulation mechanism.

PMID- 15259505
TI  - TGF-beta and p53 staining in CT-guided and endoscopic ultrasound fine-needle
      aspirates of pancreatic adenocarcinoma.
AB  - Our purpose was to determine if fine-needle aspirates of pancreatic
      adenocarcinoma would produce material amenable to tumor marker staining and to
      correlate the expression of TGF-beta and p53 with patient and tumor data. One
      hundred twenty specimens were analyzed. TGF-beta was positive in 26% of cases and
      had no correlation with patient's age, sex, survival, stage, grade, or size. p53
      was positive in 22% of the cases and correlated only with grade 1 tumors.
      Expression of TGF-beta and p53 can be tested on preserved cytologic specimens.
      This is the largest study to date correlating TGF-beta and p53 expression in
      pancreatic adenocarcinoma and patient demographics, prognosis, and tumor
      attributes. This is also the first study that did not select for surgical
      candidates. TGF-beta expression does not appear to have prognostic significance
      in pancreatic cancer. p53 was more common in well-differentiated tumors and may
      be an early mutation lost in more poorly differentiated tumors.

PMID- 15259506
TI  - Elevated resistive index in the hepatic artery as a predictor of fulminant
      hepatic failure in patients with acute viral hepatitis: a prospective study using
      Doppler ultrasound.
AB  - To assess the sensitivity and specificity of the resistive index of the hepatic
      artery, which is related to the vascular resistance of the artery, for the
      prediction of fulminant hepatic failure, we performed Doppler ultrasonography
      examinations on the hepatic arteries of 72 patients with acute viral hepatitis
      (25 of whom developed fulminant hepatic failure and 47 of whom recovered without
      developing fulminant hepatic failure) as well as the hepatic arteries of age- and
      sex-matched controls. The mean resistive index of the hepatic arteries in
      patients who developed fulminant hepatic failure was significantly larger than
      that of patients who recovered without developing fulminant hepatic failure (P <
      0.01). When a resistive index cutoff level of 0.74 was used, an 84% sensitivity
      and a 94% specificity were obtained for the prediction of fulminant hepatic
      failure. An elevated resistive index of the hepatic artery may be useful for
      predicting the patient's clinical outcome and determining the need for a liver
      transplantation in patients with acute viral hepatitis.

PMID- 15259507
TI  - Impaired hepatocyte regeneration in toll-like receptor 4 mutant mice.
AB  - Multiple lines of evidence suggest a role for endogenous lipopolysaccharides in
      toxin-induced liver injury. Toll-like receptor 4 has recently been implicated as
      a cell surface receptor important for lipopolysaccharide responsiveness. In these
      experiments, we sought to determine the role of toll-like receptor 4 in acute
      liver injury by carbon tetrachloride by utilizing the naturally occurring toll
      like receptor 4 mutant and wild-type mice strains. Mice were injected with either
      carbon tetrachloride or the carrier. Serum transaminase levels peaked at 24 hr
      after carbon tetrachloride administration for both wild-type and mutant mice,
      with no significant histological difference in initial liver injury between the
      two groups. However, an overall decrease in hepatocyte proliferation was found in
      the mutant mice. Examination of the liver tissue revealed significant decreases
      in intrahepatic expressions of proinflammatory mediators. In conclusion, our
      results suggest that toll-like receptor 4 is important in the hepatic
      regenerative response to CCl4 liver injury via its role in modulating the
      inflammatory response to hepatic injury.

PMID- 15259508
TI  - Risk factors for hepatocellular carcinoma in patients with cirrhosis.
AB  - Recent research suggests an increase in the incidence of hepatocellular carcinoma
      (HCC) in the United States, which may be related to an upsurge in the sequelae of
      chronic liver disease from hepatitis C virus. In addition to factors related to
      the underlying etiology of liver disease, a number of host factors such as age,
      gender, and ethnic background may be associated with this increased risk. The aim
      of this study was to evaluate a number of potential risk factors for HCC in
      patients with cirrhosis. Patients with biopsy proven HCC were identified from our
      pathology and cancer registry databases. All those without histologic or clinical
      cirrhosis and non-HCC hepatic malignancies were excluded. Cirrhotic patients
      without HCC were also selected from the Cleveland Clinic unified transplant
      database and were designated controls. Extensive clinicodemographic data were
      obtained from the databases and chart reviews. When available, paraffin-embedded
      liver biopsy blocks were obtained for HFE gene analysis. Univariate comparisons
      were made with chi-square and Fisher's exact test and multivariate analysis was
      carried out with logistic regression. A total of 760 patients were included in
      this study, 244 documented cases of HCC and 516 cirrhotic controls without HCC.
      Patients' age (RR = 3.1 [2.6-3.8]; P < 0.0001), male gender (RR = 3.4 [2.3-5.1];
      P < 0.0001), African-American ethnicity (RR = 3.1 [1.6-5.8]; P = 0.0005), and
      other non-Caucasian ethnicity (RR = 6.9 [3.2-14.4]; P < 0.0001) were
      independently associated with HCC. Restricting the analysis to HCV-related
      cirrhosis, the same risk factors remained independently associated with HCC: age
      (decade; RR = 2.3 [1.6-3.4]; P < 0.0001), male gender (RR = 2.9 [1.2-7.0]; P =
      0.02), African-American ethnicity (RR = 3.1 [1.3-7.4]; P = 0.009), and other non
      Caucasian ethnicity (RR = 15.8 [1.9-134]; P = 0.01). Iron studies did not reveal
      an increased risk for iron overload or HFE mutation. Male gender, advancing age,
      and non-Caucasian ethnic background are independently associated with HCC.

PMID- 15259509
TI  - Hypercoagulable states in patients with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) patients have an increased risk for venous
      thromboembolism, mainly portal venous thrombosis (PVT). The aim of this study was
      to assess the role of acquired and hereditary thrombotic risk factors in HCC
      patients. Thirty-one patients with HCC, 30 patients with cirrhosis but without
      HCC or PVT, and 48 matched healthy controls were studied. Mean levels of plasma
      protein C, protein S, antithrombin, and serum lipoprotein (a) were significantly
      lower in patients with HCC and in the cirrhotic group compared to the healthy
      controls. Mean serum homocysteine levels were significantly higher in patients
      with HCC compared to cirrhotics and healthy controls. The prevalence of activated
      protein C resistance, factor V Leiden mutation, prothrombin gene mutation
      G20210GA, and C677T methylenetetrahydrofolate reductase polymorphism was not
      significantly different among the three groups. In conclusion, thrombophilic
      defects are common in HCC patients and they might contribute to the observed
      thrombotic complications in this malignancy.

PMID- 15259510
TI  - Immune escape mechanism: defective resting and stimulated leukocyte-endothelium
      interaction in hepatocellular carcinoma of the rat.
AB  - Hepatocellular carcinoma represents an increasing therapeutic challenge due to
      its high incidence and early metastasis. Numerous studies have demonstrated the
      influence of the vascular system on tumor growth and development. In addition,
      the role of leukocyte-endothelium interaction in tumor vessels is of particular
      significance with regard to immunological tumor therapy. In this study we used an
      experimental in vivo animal model that allows a quantitative analysis on vessel
      morphology, microcirculation, and leukocyte-endothelium interaction. The vessel
      architecture in tumor tissue was found to be extremely heterogeneous, with a
      consecutively variable blood flow velocity. Following superfusion with
      chemotactic factors (fMLP, LB4), the leukocyte-endothelium interaction in tumor
      tissue with respect to leukocyte sticking was significantly reduced in comparison
      to healthy liver tissue. In conclusion, one of the main mechanisms for the
      reduced leukocyte-endothelium interaction in tumor tissue seems to be a decreased
      expression of adhesion molecules such as ICAM-1, indicating an effective immune
      escape mechanism for this tumor.

PMID- 15259511
TI  - Therapeutic management algorithm in cirrhotic and noncirrhotic patients in
      primary or secondary liver masses.
AB  - The treatment of hepatic tumors in cirrhotic and noncirrhotic patients still
      represents a major issue in decision making for oncologists and surgeons. The
      high mortality of open liver surgery, particularly in cirrhotic patients, has
      pushed physicians to research new modalities. In this review paper we summarize
      the available and alternative methods for the treatment of liver masses using new
      modalities and a minimally invasive approach, which will benefit the quality of
      life of the patients. We also outline therapeutic plan options.

PMID- 15259512
TI  - Relationship of abuse history and other risk factors with obesity among female
      gastrointestinal patients.
AB  - Little is know about the relationship of abuse history and other risk factors
      with being overweight and obese among gastrointestinal patients. The purpose of
      this study was to assess the relative risk of abuse history on being overweight
      and obese among 239 female gastrointestinal patients. Forty-one percent of the
      patients were found to be overweight or obese, 49% reported a history of physical
      abuse, and 42% had a sexual abuse history. A history of physical abuse (odds
      ratio = 1.34, P < 0.03), being nonwhite (odds ratio = 2.66, P < 0.01), being
      older (odds ratio = 1.03 for each year older, P < 0.02), and having fewer years
      of schooling (odds ratio = 1.11, P < 0.05) were found to be strongly associated
      with being overweight and/or obese. Among the female patients referred for
      gastrointestinal disorders at a university-based gastrointestinal clinic, a high
      proportion was overweight or obese. Physical abuse history and several
      demographic factors were significantly related to being overweight and obese in
      this clinical population.

PMID- 15259513
TI  - Comparative studies of superoxide production by microbial wall product-primed
      neutrophils in ulcerative colitis.
AB  - A diminished tolerance to the normal gut bacterial flora has been suggested to be
      pathogenic in ulcerative colitis (UC) and the aim of this study was to evaluate
      the priming effect of selected bacterial wall products on UC neutrophil
      granulocytes. Neutrophils from 10 UC patients and 10 healthy controls were primed
      with bacterial lipoprotein (BLP) or lipopolysaccharide (LPS) and subsequently
      activated. Extracellular superoxide production was measured by the cytochrome c
      reduction assay. Priming neutrophils with BLP or LPS dose dependently increased
      the superoxide production in both UC and controls (P < 0.01), and BLP was more
      potent than LPS (P < 0.05). No differences were found between UC and controls. UC
      neutrophils do not seem to have an intrinsic abnormality with reduced tolerance
      to bacterial substances. However, bacterial wall products such as BLP modify
      neutrophil tissue-destruction mechanisms and might be pivotal for perpetuation of
      chronic colonic inflammation.

PMID- 15259514
TI  - Perforation of a solitary diverticulum of sigmoid colon in an incarcerated
      scrotal hernia.

PMID- 15259515
TI  - Severe recurrent gastrointestinal bleeding due to angiodysplasia in a Bernard
      Soulier patient: an onerous medical concomitance.

PMID- 15259516
TI  - Comparison of fentanyl versus meperidine for analgesia in pediatric
      gastrointestinal endoscopy.
AB  - This study compared the safety and efficacy of fentanyl and meperidine for
      analgesia in pediatric gastrointestinal endoscopy. In a double-blind, randomized
      trial, 24 patients (11 males) received either fentanyl (1 microg/kg) or
      meperidine (1 mg/kg). These analgesics were administered in unmarked syringes by
      an investigator who did not participate in the procedure or in the evaluation of
      the patient's sedation. There were 17 Caucasians and 7 African-Americans whose
      mean age was 10.4 +/- 4.4 years. Thirteen patients received meperidine and 11
      received fentanyl. Midazolam was given to all patients as needed to provide
      sufficient sedation for the procedure. Study subjects underwent EGD (n = 17) or
      colonoscopy (n = 7). There were no differences as assessed by patient,
      endoscopist, or assistant for tolerance, discomfort, procedure ease, recovery
      time, complications, heart rate, blood pressure, or oxygen saturation. We
      conclude that meperidine and fentanyl are equally effective in providing
      analgesia for pediatric gastrointestinal endoscopy.

PMID- 15259517
TI  - Recurrent diplopia after consuming alcoholic beverages.

PMID- 15259518
TI  - Is ophthalmologic follow-up for corneal abrasions needed?

PMID- 15259519
TI  - Effects of omega-3 fatty acids on cardiovascular health.

PMID- 15259520
TI  - Should risk factors for breast cancer influence evaluation of breast
      abnormalities?

PMID- 15259521
TI  - Medical methods for first-trimester abortion.

PMID- 15259522
TI  - Gowning in newborn and special-care nurseries.

PMID- 15259523
TI  - Intensive management of gestational diabetes.

PMID- 15259524
TI  - Travel immunizations.
AB  - Advising travelers on vaccine-preventable illnesses is increasingly becoming the
      responsibility of primary care physicians. The approach to vaccine
      recommendations should be based on a thorough assessment of the risks for travel
      related diseases, the time available before trip departure, and current knowledge
      of the epidemiology of vaccine-preventable diseases. Routine childhood
      vaccinations should be reviewed in all travelers and updated as necessary. Yellow
      fever vaccination may be required for entry by countries that lie within a yellow
      fever zone or for travelers coming from an endemic area to prevent introduction
      of the disease. Immunization against hepatitis B virus should be considered in
      travelers who expect to have close contact with local populations that have high
      rates of hepatitis B transmission. Japanese encephalitis vaccine should be
      offered to travelers who plan prolonged trips to rural areas in southeast Asia or
      the Indian subcontinent during the transmission season. Typhoid fever
      immunization is recommended for travelers who may be exposed to potentially
      contaminated food and drink. Preexposure rabies vaccination should be considered
      in travelers who plan a prolonged duration of stay in a remote area or who engage
      in activities that might involve working near animals or that could attract
      animals. Physicians should be aware of the adverse events and contraindications
      associated with each travel vaccine.

PMID- 15259525
TI  - Information from your family doctor. Travel vaccines.

PMID- 15259526
TI  - Evaluation and management of nonulcer dyspepsia.
AB  - When no organic cause for dyspepsia is found, the condition generally is
      considered to be functional, or idiopathic. Nonulcer dyspepsia can cause a
      variety of symptoms, including abdominal pain, bloating, nausea, and vomiting.
      Many patients with nonulcer dyspepsia have multiple somatic complaints, as well
      as symptoms of anxiety and depression. Extensive diagnostic testing is not
      recommended, except in patients with serious risk factors such as dysphagia,
      protracted vomiting, anorexia, melena, anemia, or a palpable mass. In these
      patients, endoscopy should be considered to exclude gastroesophageal reflux
      disease, peptic or duodenal ulcer, and gastric cancer. In patients without risk
      factors, consideration should be given to empiric therapy with a prokinetic agent
      (e.g., metoclopramide), an acid suppressant (histamine-H2 receptor antagonist),
      or an antimicrobial agent with activity against Helicobacter pylori. Treatment of
      patients with H. pylori infection and nonulcer dyspepsia (rather than peptic
      ulcer) is controversial and should be undertaken only when the pathogen has been
      identified. Psychotropic agents should be used in patients with comorbid anxiety
      or depression. Treatment of nonulcer dyspepsia can be challenging because of the
      need to balance medical management strategies with treatments for psychologic or
      functional disease.

PMID- 15259527
TI  - Management of corneal abrasions.
AB  - Corneal abrasions result from cutting, scratching, or abrading the thin,
      protective, clear coat of the exposed anterior portion of the ocular epithelium.
      These injuries cause pain, tearing, photophobia, foreign body sensation, and a
      gritty feeling. Symptoms can be worsened by exposure to light, blinking, and
      rubbing the injured surface against the inside of the eyelid. Visualizing the
      cornea under cobalt-blue filtered light after the application of fluorescein can
      confirm the diagnosis. Most corneal abrasions heal in 24 to 72 hours and rarely
      progress to corneal erosion or infection. Although eye patching traditionally has
      been recommended in the treatment of corneal abrasions, multiple well-designed
      studies show that patching does not help and may hinder healing. Topical
      mydriatics also are not beneficial. Initial treatment should be symptomatic,
      consisting of foreign body removal and analgesia with topical nonsteroidal anti
      inflammatory drugs or oral analgesics; topical antibiotics also may be used.
      Corneal abrasions can be avoided through the use of protective eyewear.

PMID- 15259528
TI  - Information from your family doctor. Corneal abrasions.

PMID- 15259530
TI  - Counseling for breastfeeding.

PMID- 15259531
TI  - Do ACE inhibitors decrease mortality in patients with hypertension?

PMID- 15259529
TI  - Omega-3 fatty acids.
AB  - Omega-3 fatty acids have been shown to significantly reduce the risk for sudden
      death caused by cardiac arrhythmias and all-cause mortality in patients with
      known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil
      are rich sources of the omega-3 fatty acids eicosapentaenoic acid and
      docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary
      sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3
      fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty
      acids, which are present in most seeds, vegetable oils, and meat, are
      prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat
      hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant
      drug interactions with omega-3 fatty acids. The American Heart Association
      recommends consumption of two servings of fish per week for persons with no
      history of coronary heart disease and at least one serving of fish daily for
      those with known coronary heart disease. Approximately 1 g per day of
      eicosapentaenoic acid plus docosahexaenoic acid is recommended for
      cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce
      elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness
      and the number of tender joints in patients with rheumatoid arthritis (at least 3
      g per day). Modest decreases in blood pressure occur with significantly higher
      dosages of omega-3 fatty acids.

PMID- 15259532
TI  - Painful red eye after surgery.

PMID- 15259535
TI  - Sleep disorders in Parkinson's disease.
AB  - Depression, dementia, and physiologic changes contribute to the high prevalence
      of sleep disturbances in patients with Parkinson's disease (PD). Antiparkinsonian
      drugs also play a role in insomnia by increasing daytime sleepiness and affecting
      motor symptoms and depression. Common types of sleep disturbances in PD patients
      include nocturnal sleep disruption and excessive daytime sleepiness, restless
      legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, sleep
      walking and sleep talking, nightmares, sleep terrors, and panic attacks. A
      thorough assessment should include complete medical and psychiatric histories,
      sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale
      evaluation. Polysomnography or actigraphy may also be indicated. Treatment should
      address underlying factors such as depression or anxiety. Hypnotic therapy for
      sleep disturbances in PD patients should be approached with care because of the
      risks of falling, agitation, drowsiness, and hypotension. Behavioral
      interventions may also be useful.

PMID- 15259536
TI  - Sleep disorders in Alzheimer's disease and other dementias.
AB  - Patients with dementias, such as Alzheimer's disease (AD), often have nocturnally
      disrupted sleep. Clinically, this may present as agitation during the nighttime
      hours, which may affect as many as a quarter of AD patients during some stage of
      their illness. Sleep disturbance in AD may be multifactorial and involve sleep
      disordered breathing and disrupted chronobiology, both often characterized by
      excessive daytime napping. Polysomnographically, AD patients show decreased rapid
      eye movement (REM) sleep in proportion to the extent of their dementia; some
      evidence suggests that cholinesterase inhibitors, commonly used pharmacologic
      agents for cognitive loss in AD, may increase REM sleep measures. Unfortunately,
      such agents may also induce insomnia and vivid dreams. There have been no
      randomized clinical trials of sedative-hypnotic medications specifically targeted
      at AD patients with sleep problems. Evidence suggests that sedative-hypnotics,
      such as benzodiazepine site-specific agonists, may have a role in some cases,
      whereas atypical antipsychotics may be necessary in other cases. There are also
      reports of successful interventions with nonpharmacologic options (eg, exercise,
      illumination). The utility of melatonin as a hypnotic in this population appears
      equivocal.

PMID- 15259537
TI  - The enigma of dental amalgam.

PMID- 15259538
TI  - Endodontic posts.

PMID- 15259539
TI  - Novel porcelain laminate preparation approach driven by a diagnostic mock-up.
AB  - One critical step in the porcelain laminate technique is the achievement of
      sufficient ceramic thickness. At least two different strategies for tooth
      preparation can be found in the literature: (1) earlier simplified techniques
      included the use of depth cutters guided by the existing tooth surface-however,
      that approach did not take into consideration alterations of the tooth owing to
      aging, wear, or loss of enamel and thus led to greater risks for dentin
      exposures; (2) more recent and sophisticated methods have integrated an additive
      diagnostic procedure (ie, wax-up or mock-up) to compensate for tooth aging or
      severe existing loss of tooth substance. This approach allows for more enamel
      preservation and, as a consequence, more predictable bonding, biomechanics, and
      esthetics. The present article illustrates in detail the latest development in
      tooth preparation for porcelain laminates. This technique combines the time
      efficiency of earliest methods with the rationale and diagnostic foundations of
      the more recent techniques. CLINICAL SIGNIFICANCE: Using this new laminate
      porcelain preparation approach, clinicians should be able to produce not only
      more accurate preparations, but also higher-quality tooth preparations in a time
      efficient fashion.

PMID- 15259540
TI  - Direct composite resin restorations: a review of some clinical procedures to
      achieve predictable results in posterior teeth.
AB  - The interest of patients in having tooth-colored restorations and the development
      of techniques and materials that make these restorations easier have contributed
      to make the esthetic restoration of posterior teeth popular. The direct use of
      composites in posterior teeth is a technique-sensitive procedure. Some
      difficulties, nevertheless, can be overcome or at least minimized by a heedful
      clinician by paying thorough attention to the various stages of the restorative
      technique. The present article seeks to review some concepts about this adhesive
      restorative procedure and to illustrate the possibilities of the technique with
      clinical reports. CLINICAL SIGNIFICANCE: The direct posterior composite
      restorative technique offers the possibility of closely matching the natural
      optical characteristics of the lost tooth structure. Aimed at showing the
      potential of this technique, this article presents two step-by-step case reports
      and also reviews some concepts related to these clinical procedures.

PMID- 15259541
TI  - Influence of phosphoric acid pretreatment on self-etching bond strengths.
AB  - PURPOSE: The purpose of this investigation was to evaluate the influence of
      phosphoric acid pretreatment on shear bond strength of two self-etching bonding
      systems to enamel and dentin. MATERIALS AND METHODS: Forty-eight extracted third
      human molar teeth were mounted, embedded into polystyrene resin, polished with
      600-grit aluminum oxide papers, and randomly divided into four groups (n = 12):
      group 1-Clearfil Liner Bond 2V (Kuraray Co. Ltd., Osaka, Japan); group 2-One Up
      Bond F (Tokuyama Corp., Tokyo, Japan); group 3-phosphoric acid (Condicionador
      Dental Gel, Dentsply Ind. Com. LTDA, Rio de Janeiro, Brazil) and Clearfil Liner
      Bond 2V; group 4-phosphoric acid and One Up Bond F. In groups 3 and 4 the
      substrate was pre-etched for 15 seconds with 37% phosphoric acid, rinsed, and
      dried with an air stream. In all groups adhesive systems were applied according
      to manufacturers' instructions and light cured; then a restorative composite
      resin (TPH Spectrum, Dentsply Ind. Com. LTDA) was placed in a polytef matrix and
      cured. The specimens were stored in humidity for 7 days at 37 degrees C. The
      shear bond strength test was performed in a universal test machine with a
      crosshead speed of 0.5 mm/min. All procedures were repeated for the dentin
      evaluation. Mean values were analyzed with two-way analysis of variance and
      Duncan tests (p < .05). RESULTS: The values obtained are listed in decreasing
      order: enamel-group 3 = 24.6 MPa, group 4 = 23.6 MPa, group 1 = 19.2 MPa, group 2
      = 8.5 MPa; dentin-group 1 = 17.2 MPa, group 2 = 16.1 MPa, group 4 = 13.1 MPa,
      group 3 = 11.3 MPa. CONCLUSIONS: Under the conditions of this study, enamel
      etching with 37% phosphoric acid provided statistically significant higher shear
      bond strength values, regardless of the adhesive system. However, in dentin, for
      Clearfil Liner Bond 2V, phosphoric acid pretreatment negatively affected bond
      strength values. CLINICAL SIGNIFICANCE: The use of self-etching systems in
      composite-to-enamel bonding restorative techniques still needs improvement when
      compared with the high bond strengths obtained with phosphoric acid treatment.
      However, lower shear bond strengths were observed in dentin when phosphoric acid
      was used in association with either adhesive system.

PMID- 15259542
TI  - Surface roughness of packable composite resins polished with various systems.
AB  - PURPOSE: The aim of this study was to evaluate the surface roughness of four
      packable composite resins, SureFil (Dentsply, Petropolis, Rio de Janeiro,
      Brazil), Prodigy Condensable (Kerr Co., Orange, CA, USA), Filtek P60 (3M do
      Brasil, Sao Paulo, Brazil), and ALERT (Jeneric/Pentron, Inc., Wallingford, CT,
      USA) and one microhybrid composite resin (Filtek Z250, 3M do Brasil) after
      polishing with four finishing systems. MATERIALS AND METHODS: Twenty specimens
      were made of each material (5 mm in diameter and 4 mm high) and were analyzed
      with a profilometer (Perthometer S8P, Perthen, Mahr, Germany) to measure the mean
      surface roughness (Ra). The specimens were then divided into four groups
      according to the polishing system: group 1--Sof-Lex (3M do Brasil), group 2-
      Enhance (Dentsply), group 3--Composite Finishing Kit (KG Sorensen, Barueri, Sao
      Paulo, Brazil), and group 4--Jiffy Polisher Cups (Ultradent Products, Inc., South
      Jordan, UT, USA). The specimens were polished and then evaluated for Ra, and the
      data were subjected to analysis of variance, analysis of covariance, and Tukey's
      test (p = .05). RESULTS: The mean Ra of SureFil polished with Sof-Lex was
      significantly lower than that of KG points. Prodigy Condensable polished with
      Enhance showed a significantly less rough surface than when polished with Sof
      Lex. Filtek P60 did not exhibit a significant difference with the various
      polishing systems. For ALERT the lowest mean Ra was obtained with Sof-Lex and the
      highest mean Ra with KG points. Regarding Filtek Z250, polishing with KG and
      Jiffy points resulted in a significantly lower mean Ra than when polished with
      Enhance. CONCLUSIONS: Packable composite resins display variable roughness
      depending on the polishing system used; the Sof-Lex disks and Jiffy points
      resulted in the best Ra values for the majority of the materials tested. CLINICAL
      SIGNIFICANCE: The Sof-Lex disks and the Jiffy points produced the smoothest
      surfaces for the tested resin composites. As a result, they should be considered
      for clinical use as preferred polishing systems for these resin composites.

PMID- 15259543
TI  - Desensitizing agent efficacy during whitening in an at-risk population.
AB  - BACKGROUND: Nightguard vital bleaching (NGVB) has gained acceptance among
      dentists and patients as a simple and effective procedure to lighten discolored
      teeth. Although the efficacy and predictability of NGVB have been well
      established, it has been documented that patients undergoing the procedure may
      experience side effects such as tooth sensitivity (TS) and gingival irritation
      (GI). A previous NGVB study suggested that selected participants might benefit
      from a regimen of a desensitizing agent (DSA) to decrease or prevent TS during
      whitening. PURPOSE: The purpose of this study was to determine whether the daily
      use of an active DSA (UltraEZ, Ultradent Products Inc., South Jordan, UT, USA)
      during NGVB would decrease TS in a population at risk for TS when compared with a
      placebo. MATERIALS AND METHODS: Forty subjects participated in this single-blind
      randomized clinical trial. All participants had indicated that they had
      preexisting TS or other risk factors for TS during NGVB. To evaluate TS caused by
      the tray alone, participants wore custom-fitted maxillary whitening trays
      containing no DSA or whitening solution during week 1. Next, participants were
      randomly assigned to apply either the active DSA or placebo daily for 14 days in
      the trays for 30 minutes prior to whitening. The placebo was the same formulation
      as UltraEZ but without the desensitizing agents (3% potassium nitrate and 0.11%
      by weight fluoride ion). The bleaching solution was a 10% carbamide peroxide
      whitening solution (Opalescence, Ultradent Inc.). Post treatment, participants
      were followed up for 1 week, during which time they used neither trays nor
      solutions. Throughout the study, participants completed a daily diary to record
      their perceptions of TS and the time spent wearing the tray with the whitening
      solution. RESULTS: Forty-one percent of the active group had at least 1 day of TS
      during treatment compared with 78% of the placebo group. The difference was
      statistically significant (p = .027) using the two-tailed Fisher exact test.
      CLINICAL SIGNIFICANCE: This study suggests that the use of an active 3% potassium
      nitrate and 0.11% fluoride desensitizing agent for 30 minutes prior to whitening
      may decrease tooth sensitivity when compared with a placebo in a population at
      risk for tooth sensitivity.

PMID- 15259544
TI  - Positioning self-etching adhesives: versus or in addition to phosphoric acid
      etching?

PMID- 15259545
TI  - Talking with patients. Dental caries.

PMID- 15259546
TI  - Thirty years of limb salvage.

PMID- 15259547
TI  - The use of a closed expandable prosthesis for pediatric sarcomas.
AB  - PURPOSE: The purpose of this paper is to review our experience with a non
      invasive expandable prosthesis for skeletally immature patients following limb
      salvage for malignant tumors about the knee. MATERIALS & METHODS: Between 1998
      and 2002, Repiphysis prostheses (Wright Medical Technology, Memphis, Tenn.) were
      implanted in 18 patients. 16 patients had at least 12 months follow-up. There
      were 10 males and 8 females. The diagnosis was Stage IIB osteosarcoma in all
      patients. Sites included femur 14, and 4 proximal tibias. The average age was
      10.7 years (range 8-16); the average age for males was 12 years and females, 9
      years. Fifteen of the prostheses were implanted at the time of surgical resection
      and the remainder was conversions of previous surgery. RESULTS: Follow-up
      averaged 24.8 months (range 12-47). Fourteen patients have undergone a total of
      58 lengthening procedures. Average expansion 38 mm per patient (range, 10-76 mm).
      An average of 8.5 mm per lengthening procedure. There was only one failure to
      lengthen. ISOLS functional scores averaged 83.5%. For those with a current
      functional prosthesis, the ISOLS score averaged 94%. Three patients have reached
      maximal expansion and converted to a conventional prosthesis. There were
      complications in 7 patients: 2 expandable component fractures, 1 femoral
      component fracture, 2 stem fractures, 1 stem loosening and 1 deep infection. Of
      the two expandable component fractures, 1 patient reached full expansion and was
      converted to an endoprosthesis. The femoral component fracture and 2 stem
      fractures were revised to a new prosthesis 13 months post-op and are functioning
      well. The 1 loose stem was revised to an APC. CONCLUSIONS: The Repiphysis
      prosthesis utilizes energy stored in a spring that is held compressed by a
      locking mechanism. Controlled release of the locking mechanism via an external
      electromagnetic field allows for lengthening of the device. In our early
      experience, the functional results were excellent similar to conventional modular
      devices. Complications should be anticipated but are salvageable. This device
      allows limb salvage in pediatric patients when amputation would be otherwise
      chosen.

PMID- 15259548
TI  - How to improve the incorporation of massive allografts?
AB  - The incorporation of a bone graft is the result of creeping and substitutional
      activities that remove the original grafted bone and replace it by newly formed
      bone from the host cells. However, this intricate process is very limited in time
      and space. A bone allograft is poorly remodeled and is almost non viable even
      after several years of implantation. This lack of vitality accounts for the high
      rate of complications such as non union and fracture. One way to minimize the
      allograft complications is to improve its incorporation. The process of
      incorporation in animals and human beings is reviewed as well as the various
      avenues for a biologic improvement either through modulation on the host: the
      immune response, the inhibition of bone resorption, the use of bone morphogenetic
      proteins, the autogenous cell augmentation or through processing the bone
      allograft: bisphosphonate adsorption or bone perforations. In 2002, biologic
      enhancement of the incorporation is still in its infancy but will be in a near
      future a reality through influence on both the host and the allograft.

PMID- 15259549
TI  - Bacterial contamination of musculoskeletal allografts.
AB  - Based on the indications in the literature of the transmission of highly
      pathogenic bacteria in musculoskeletal allograft implants, the cultural results
      for allografts removed and implanted in conditions of asepsis between 1997 and
      2000 in BTM were analyzed: 4014 allografts (3117 from a living donor, 897 from a
      cadaver) and 3479 implants (2191 with allografts from living donors and 1288 with
      allografts from cadavers). Explanted tissues: these were positive to culture in
      292 out of 3117 (9.4%) allografts from living donors; the bacteria isolated
      showed low pathogenicity. Out of 897 allografts 117 cadaver donors bacteria with
      low pathogenicity were isolated in 68 (7.6%) and high pathogenicity in 12 (1.3%).
      Implants: cultures were positive in 116/2191 (5.3%) implants with allografts from
      living donors and in 55/1288 (4.3%) implants with allografts from cadavers. The
      bacteria isolated are the same as those shown in the explants. In living donors
      contamination is similar as regards incidence and type of microorganism to that
      observed in surgical theatres during routine surgery. Contamination seems to be
      greater in allografts removed from cadavers who died as a result of trauma, in
      the presence of positive hemocultures, prolonged catheterization and intubation,
      explantation of the pelvis and removal of several organs and tissues prior to
      musculoskeletal allograft.

PMID- 15259550
TI  - Tissue engineering for cartilage repair: in vitro properties of a hyaluronan
      derivative.
AB  - Association of biomaterials with autologous cells can provide a new generation of
      implantable devices for cartilage and bone repair. Such scaffolds should provide
      a performed three-dimensional shape, prevent cells from floating out of the
      defect, have sufficient mechanical strength, facilitate uniform spread of cells,
      and stimulate the phenotype of transplanted cells. Hyaff-11 is a recently
      developed hyaluronic-acid based biodegradable polymer, that has been shown to
      provide successful cell scaffolds for tissue-engineered repair. The aim of this
      study was to evaluate in vitro the potential of Hyaff-11 to support the growth of
      human chondrocytes and to maintain their original phenotype. Our data indicate
      that human chondrocytes seeded on Hyaff-11 express and produce collagen type II
      and aggrecan and downregulate the production of collagen type I. These results
      provide an in vitro demonstration of therapeutic potential of Hyaff-11 as a
      delivery vehicle in tissue-engineered repair of articular cartilage defects.

PMID- 15259551
TI  - Establishment of a new human immortalized chondrocyte cell line.
AB  - Chondrocytes from human adult articular healthy cartilage were transfected in
      primary culture with a plasmid containing two human papilloma virus type 16 early
      function genes: E6 and E7, using the highly efficient cationic liposome-mediated
      (lipofection) procedure. The transfection was verified by reverse transcriptase
      polymerase chain reaction analysis of E7 mRNA and by immunofluorescence
      localization of the E7 protein in the cell cytoplasm. The established chondrocyte
      cell line was examined in monolayer and in two culture conditions that were
      described to re-induce differentiated characteristics: culturing in a serum-free
      defined medium and seeding on a hyaluronan-based three-dimensional biomaterial.
      Immortalized cells were able to re-express the main markers of chondrocyte
      phenotype, both at mRNA and protein levels, under the two defined cultured
      conditions used. The cell line that we obtained may be a useful tool for
      increasing our knowledge of the genetic and biochemical events involved in the
      processes of cartilage growth and differentiation, and of the etiopathogenesis of
      many rheumatic diseases.

PMID- 15259552
TI  - Hyaluronan-based biomaterial (Hyaff-11) as scaffold to support mineralization of
      bone marrow stromal cells.
AB  - Various techniques are widely used to repair bone defects, association of
      hyaluronan-based biodegradable polymers (Hyaff-11) with bone marrow stromal cells
      (BMSC) promises to provide successful cell scaffolds for tissue-engineered repair
      of bone tissue. We evaluate in vitro and in vivo the potential of Hyaff-11 to
      facilitate mineralization of BMSC. Rat BMSC were seeded on Hyaff-11 and their
      differentiation were assessed at different time points. Osteogenic
      differentiation was investigated in vitro analysing the expression of alkaline
      phosphatase and osteocalcin. Mineralization of bone defects was evaluated also in
      vivo implanting Hyaff-11 scaffold combined with BMSC in large segmental radius
      defects. In vitro, we found a decrease expression of alkaline phosphatase and an
      increase of osteocalcin. In vivo, our data showed that mineralization was induced
      and basic fibroblast growth factor contributed to this process. These results
      provide a demonstration to therapeutic potential of Hyaff-11 as appropriate
      carrier vehicle for differentiation and mineralization of BMSC and for the repair
      of bone defects.

PMID- 15259553
TI  - Ceramic-ceramic coupling. Total hip arthroplasty in young patients.
AB  - Between 1994 and 2000 at the 7th Division of the Rizzoli Orthopaedic Institute a
      total of 123 total hip arthroplasties were implanted in 105 patients aged under
      40 years (mean age 32 years). In most of the cases the patient was affected with
      osteoarthrosis secondary to congenital hip dysplasia (35%) or osteonecrosis
      (29%). In all of the cases the same type of cup was press-fitted with alumina on
      alumina bearing surfaces. The stem was cemented in 4 cases. Six of the patients
      were submitted to prosthetic revision surgery: 1 as a result of deep infection, 2
      recurring dislocation, 3 aseptic loosening of one of the components. Radiographic
      evaluation did not reveal signs of periprosthetic osteolysis. We did not observe
      any cases of rupture of the alumina head or any problems related to the
      modularity of the implant. The authors wish to stress the reliability of using
      alumina on alumina in a population with high functional demand.

PMID- 15259554
TI  - Trochanteric arthroplasty in the treatment of sequelae after septic arthritis of
      the hip in infancy.
AB  - The authors describe 17 patients submitted to trochanteric arthroplasty between
      1979 and 1999 at the Division of Pediatric Orthopaedics and Traumatology of the
      Rizzoli Orthopaedic Institute. There were 9 females and 8 males aged from 1 to 8
      years (mean of 4) affected with the sequelae of septic arthritis of the hip with
      complete destruction of the epiphysis and of the femoral neck (types IVB and V
      according to the Hunka classification system). Mean follow-up was 9 years
      (minimum 1, maximum 23). Surgery is described and indications are discussed: this
      is the only type of treatment that may be offered in place of conservative
      treatment.

PMID- 15259555
TI  - Osteorticular amyloidosis in a patient under dialysis treated by total hip
      arthroplasty: case report and review of the literature.
AB  - The authors present the case of a patient affected by kidney failure, who had
      been undergoing dialysis for several years when areas of osteolysis and bone
      resorption in the proximal femur and pathologic fracture appeared. She was
      treated surgically by hybrid total hip arthroplasty. The patient also complained
      of pains in other joints. The bone tissue taken from the osteolytic area was
      examined histologically. The test showed the presence of an amyloid substance.
      Microradiography and X-ray diffractometry carried out on the same samples
      confirmed the lack of mineralisation due to the presence of aluminum ions,
      presumably derived from dialysis. The high concentration of this element was
      confirmed by resum assay with spectrophometry in atomic absorption. Considering
      the results of the aforementioned tests, the patient was put on dialysis using a
      polymethylmethacrylate filter.

PMID- 15259557
TI  - Four-part displaced proximal humeral fractures: treatment with hemiarthroplasty.
AB  - Between 1996 and 2000 a total of 25 hemiarthroplasties of the shoulder in just as
      many patients were carried out. A total of 15 were followed-up (minimum 1 year,
      maximum 5 years, mean 2.5 years; mean age 75.5 years). The Constant score showed
      a mean of 73.26 points (with a maximum score of 90 and a minimum of 40). One
      patient obtained a reduced Constant score (40 points) because of severe lesions
      of the rotator cuff and continuous pain, even during the night. Patients reported
      that they were satisfied in 75% of cases. We believe that the integrity of the
      cuff is an essential condition for final success, alongside important indications
      such as type of fracture, bone quality, age and motivations of the patient, with
      respect for rules governing method of implantation and protocols for
      rehabilitation used.

PMID- 15259556
TI  - Fractures and dislocations of the lower cervical spine: surgical treatment. A
      review of 83 cases.
AB  - The authors examine 83 consecutive cases of fracture and dislocation of the lower
      cervical spine submitted to surgery over a period of 5 years. Sixty-five patients
      were monitored with minimum 5-months follow-up, 5 died, 13 could not be traced.
      Lesions were classified based on the method proposed by Argenson3 with the
      purpose of identifying guidelines for surgical treatment. Thus, different methods
      are proposed based on the type of lesion and on any neurologic deficit.
      Intersomatic fusion with anterior approach is the method of choice in most
      lesions. The exception to this is monoarticular dislocations that cannot be
      reduced, so that reduction by posterior approach associated with discectomy and
      anterior fusion are recommended. Circumferential fusion is proposed for traumatic
      spondylolistheses, complete dislocations with unsatisfactory anterior reduction,
      in lesions in flexion-extension and rotation associated with complete spinal cord
      injury, in order to favor functional rehabilitation free from ortheses. The need
      to review many cases of traumatic lesions of the lower cervical spine (LCS)
      collected over a relatively short period of time derives from the need to
      identify guidelines that will help the surgeon in his or her choice of the type
      of surgery to perform on the patient with emergency injury. The basic premise, as
      for other sites of traumatic injury, resides in an efficient classification
      (corresponding to the anatomic injury and of immediate and intuitive application)
      to which options for treatment may be related. In particular, an evaluation of
      the type of approach (anterior, posterior, combined) and of the sequence of
      surgical stages is essential to obtaining effective results with an acceptable
      complication rate. Finally, treatment must be definitive, and in cases of severe
      spinal cord injury it must allow for rapid rehabilitation and freedom from the
      use of ortheses.

PMID- 15259558
TI  - The torsion angle of the patellar tendon. A new CT parameter used for
      classification and treatment planning in femoropatellar syndrome.
AB  - The authors report a study conducted on 107 CT scans taken between January and
      December 2001 in 76 patients affected with femoropatellar pain, that did not
      benefit from physiotherapy. It is the purpose of this study to present a new CT
      scan parameter denominated torsion angle of the patellar tendon (TAPT) and to
      define an algorithm of treatment for this complex pathology based on the changes
      revealed by CT scan according to the Lyonese protocol. CT scan based on the
      Lyonese protocol provides an explanation of the symptoms and the objectivity via
      traditional parameters in 59.63% of patients. Thanks to the introduction of this
      new parameter (TAPT), which allows us to reveal the presence of an extrarotation
      of the proximal metaphysis of the tibia, the percentage of sensitivity with CT
      scan has been increased to 83.92%.

PMID- 15259559
TI  - Neurogenic arthropathy of the knee due to chronic alcoholism: two case reports.
AB  - The authors report two cases of neurogenic arthropathy of the knee in patients
      affected by chronic alcoholism. The aim of the authors is to discuss the
      etiopathogenic theory (neurotraumatic or/and neurovascular) as well as the
      mechanism by which alcohol damages joints.

PMID- 15259560
TI  - Post-traumatic osteolysis of the pubis: clinical case.

PMID- 15259561
TI  - Visual processing of the zebrafish optic tectum before and after optic nerve
      damage.
AB  - Although the zebrafish has become an important model in visual neuroscience,
      little has been done to examine the processing of its higher visual centers. The
      purpose of this work was twofold. The first purpose was to examine the physiology
      of the zebrafish retinotectal system and its relationship to retinal physiology.
      Spectral sensitivity functions were derived from visually evoked tectal responses
      and these functions were compared to the functions of electroretinogram (ERG)
      responses obtained using the same stimulus conditions. The second purpose was to
      examine the recovery of visual functioning of the tectum following optic nerve
      damage. The optic nerves of adult zebrafish were damaged (crushed), and tectal
      visual processing was assessed following damage. The results showed that the
      spectral sensitivity functions based on the On-responses of the tectum and ERG
      were qualitatively similar. The functions based on each response type received
      similar cone contributions including both nonopponent and opponent contributions.
      However, the spectral sensitivity functions based on the Off-responses of the
      tectum and ERG differed. The results also showed that the zebrafish visual system
      is capable of neural regeneration. By 90 days following an optic nerve crush, the
      spectral sensitivity function based on the tectal On-response was similar to
      functions obtained from normal zebrafish. Although the tectal Off-response did
      recover, the spectral sensitivity based on the Off-response was not the same as
      the function of normal zebrafish. These results support the notion that different
      levels of the visual system process information differently and that the
      zebrafish visual system, like those of other lower vertebrates, is capable of
      functional regeneration.

PMID- 15259562
TI  - Identification of retinal neurons in a regressive rodent eye (the naked mole
      rat).
AB  - The retina consists of many parallel circuits designed to maximize the gathering
      of important information from the environment. Each of these circuits is
      comprised of a number of different cell types combined in modules that tile the
      retina. To a subterranean animal, vision is of relatively less importance.
      Knowledge of how circuits and their elements are altered in response to the
      subterranean environment is useful both in understanding processes of regressive
      evolution and in retinal processing itself. We examined common cell types in the
      retina of the naked mole-rat, Heterocephalus glaber with immunocytochemical
      markers and retrograde staining of ganglion cells from optic nerve injections.
      The stains used show that the naked mole-rat eye has retained multiple ganglion
      cell types, 1-2 types of horizontal cell, rod bipolar and multiple types of cone
      bipolar cells, and several types of common amacrine cells. However, no labeling
      was found with antibodies to the dopamine-synthesizing enzyme, tyrosine
      hydroxylase. Although most of the well-characterized mammalian cell types are
      present in the regressive mole-rat eye, their structural organization is
      considerably less regular than in more sighted mammals. We found less precision
      of depth of stratification in the inner plexiform layer and also less precision
      in their lateral coverage of the retina. The results suggest that image formation
      is not very important in these animals, but that circuits beyond those required
      for circadian entrainment remain in place.

PMID- 15259563
TI  - An examination of the variables that affect express saccade generation.
AB  - The frequency with which express saccades are generated under a variety of
      conditions in rhesus monkeys was examined. Increasing the gap time between
      fixation spot termination and target onset increased express saccade frequency
      but was progressively less effective in doing so as the number of target
      positions in the sample was increased. Express saccades were rarely produced when
      two targets were presented simultaneously and the choice of either of which was
      rewarded; a temporal asynchrony of only 17 ms between the targets reinstated
      express saccade generation. Express saccades continued to be generated when the
      vergence or pursuit systems was coactivated with the saccadic system.

PMID- 15259564
TI  - L-type calcium channels mediate transmitter release in isolated, wide-field
      retinal amacrine cells.
AB  - Transmitter release in neurons is triggered by intracellular Ca2+ increase via
      the opening of voltage-gated Ca2+ channels. Here we investigated the voltage
      gated Ca2+ channels in wide-field amacrine cells (WFACs) isolated from the white
      bass retina that are functionally coupled to transmitter release. We monitored
      transmitter release through the measurement of the membrane capacitance (Cm). We
      found that 500-ms long depolarizations of WFACs from -70 mV to 0 mV elicited
      about a 6% transient increase in the Cm or membrane surface area. This Cm jump
      could be eliminated either by intracellular perfusion with 10 mM BAPTA or by
      extracellular application of 4 mM cobalt. WFACs possess N-type and L-type voltage
      gated Ca2+ channels. Depolarization-evoked Cm increases were unaffected by the
      specific N-type channel blocker omega-conotoxin GVIA, but they were markedly
      reduced by the L-type blocker diltiazem, suggesting a role for the L-type channel
      in synaptic transmission. Further supporting this notion, in WFACs the synaptic
      protein syntaxin always colocalized with the pore-forming subunit of the retinal
      specific L-type channels (Cav1.4 or alpha1F), but never with that of the N-type
      channels (Cav2.2 or alpha1B ).

PMID- 15259566
TI  - The type 1 polyaxonal amacrine cells of the rabbit retina: a tracer-coupling
      study.
AB  - The type 1 polyaxonal (PA1) cell is a distinct type of axon-bearing amacrine cell
      whose soma commonly occupies an interstitial position in the inner plexiform
      layer; the proximal branches of the sparse dendritic tree produce 1-4 axon-like
      processes, which form an extensive axonal arbor that is concentric with the
      smaller dendritic tree (Dacey, 1989; Famiglietti, 1992a,b). In this study,
      intracellular injections of Neurobiotin have revealed the complete dendritic and
      axonal morphology of the PA1 cells in the rabbit retina, as well as labeling the
      local array of PA1 cells through homologous tracer coupling. The dendritic-field
      area of the PA1 cells increased from a minimum of 0.15 mm2 (0.44-mm equivalent
      diameter) on the visual streak to a maximum of 0.67 mm2 (0.92-mm diameter) in the
      far periphery; the axonal-field area also showed a 3-fold variation across the
      retina, ranging from 3.1 mm2 (2.0-mm diameter) to 10.2 mm2 (3.6-mm diameter). The
      increase in dendritic- and axonal-field size was accompanied by a reduction in
      cell density, from 60 cells/mm2 in the visual streak to 20 cells/mm2 in the far
      periphery, so that the PA1 cells showed a 12 times overlap of their dendritic
      fields across the retina and a 200-300 times overlap of their axonal fields.
      Consequently, the axonal plexus was much denser than the dendritic plexus, with
      each square millimeter of retina containing approximately 100 mm of dendrites and
      approximately 1000 mm of axonal processes. The strong homologous tracer coupling
      revealed that approximately 45% of the PA1 somata were located in the inner
      nuclear layer, approximately 50% in the inner plexiform layer, and approximately
      5% in the ganglion cell layer. In addition, the Neurobiotin-injected PA1 cells
      sometimes showed clear heterologous tracer coupling to a regular array of small
      ganglion cells, which were present at half the density of the PA1 cells. The PA1
      cells were also shown to contain elevated levels of gamma-aminobutyric acid
      (GABA), like other axon-bearing amacrine cells.

PMID- 15259565
TI  - Physiological response properties of displaced amacrine cells of the adult ferret
      retina.
AB  - The ganglion cell layer (GCL) of the mammalian retina contains a large number of
      neurons called displaced amacrine cells (DACs) that do not project to the optic
      nerve. However, with the exception of the rabbit starburst amacrine cell little
      is known regarding the function of this large population due to the difficulty
      experienced in making physiological recordings from these neurons. We have
      overcome these difficulties and have used whole-cell patch-clamp techniques to
      examine the intrinsic membrane properties of DACs in the ferret retina. Our
      results indicate a large degree of diversity in their intrinsic membrane
      properties. In response to maintained depolarizing current injection, DACs
      responded with graded depolarization or by eliciting either transient or
      sustained bursts of spiking activity. At the resting membrane potential, 10% of
      the DACs generated spontaneous spikes in either an apparently random manner or at
      the peak of intrinsic waves of depolarization. The resting membrane activity of
      the remaining DACs recorded could be classified into three groups that were
      quiescent (28%), had robust uncorrelated synaptic activity (30%), or underwent
      slow waves of depolarization (42%). Diversity was also revealed in the membrane
      currents recorded in voltage-clamp where some DACs were quiescent (19%), or
      exhibited robust nonrhythmic synaptic events (42%). The remaining DACs exhibited
      waves of oscillatory activity (39%), characterized by either rhythmic bursts of
      synaptic events (17%) or slow inward currents (22%). Bath application of 50
      microM biccuculine or 150 microM picrotoxin had no effect on the waves of
      activity, however, the gap junction blocker, carbenoxolone (100 microm), blocked
      both oscillatory patterns. By including Lucifer yellow and biocytin in the
      recording pipette, it was possible to determine the morphology of recorded
      neurons and group them based on dendritic extent as small-, medium-, or large
      field DACs. There were few relationships between these morphologically defined
      groups and their intrinsic membrane properties. The present study provides the
      first in-depth examination of the intrinsic membrane properties of DACs in the
      ferret retina and provides new insights into the potential roles these neurons
      play in the processing of visual information in the mammalian retina.

PMID- 15259567
TI  - Immuocytochemical analysis of spatial organization of photoreceptors and amacrine
      and ganglion cells in the tiger salamander retina.
AB  - In the present study, using double- or triple-label immunocytochemistry in
      conjunction with confocal microscopy, we aimed to examine the population and
      distribution of photoreceptors, GABAergic and glycinergic amacrine cells, and
      ganglion cells, which are basic but important parameters for studying the
      structure-function relationship of the salamander retina. We found that the outer
      nuclear layer (ONL) contained 82,019 +/- 3203 photoreceptors, of which 52% were
      rods and 48% were cones. The density of photoreceptors peaked at approximately
      8000 cells/mm2 in the ventral and dropped to approximately 4000 cells/mm2 in the
      dorsal retina. In addition, the rod/cone ratio was less than 1 in the central
      retina but larger than I in the periphery. Moreover, in the proximal region of
      the inner nuclear layer (INL3), the total number of cells was 50,576 +/- 8400.
      GABAergic and glycinergic amacrine cells made up approximately 78% of all cells
      in this layer, including 43% GABAergic, 32% glycinergic, and 3% GABA/glycine
      colocalized amacrine cells. The density of these amacrine cells was approximately
      6500 cells/mm2 in the ventral and approximately 3200 cells/mm2 in the dorsal
      area. The ratio of GABAergic to glycinergic amacrine cells was larger than 1.
      Furthermore, in the ganglion cell layer (GCL), among a total of 36,007 +/- 2010
      cells, ganglion cells accounted for 65.7 +/- 1.5% of the total cells, whereas
      displaced GABAergic and glycinergic amacrine cells comprised about 4% of the
      cells in this layer. The ganglion cell density was approximately 1800 cells/mm2
      in the ventral and approximately 600 cells/mm2 in the dorsal retina. Our data
      demonstrate that all three major cell types are not uniformly distributed across
      the salamander retina. Instead, they exhibit a higher density in the ventral than
      in the dorsal retina and their spatial arrangement is associated with the retinal
      topography. These findings provide a basic anatomical reference for the
      electrophysiological study of this species.

PMID- 15259568
TI  - Role of the cervico-ocular reflex in the "flying" pigeon: interactions with the
      optokinetic reflex.
AB  - We studied the cervico-ocular reflex (COR) alone and in combination with the
      optokinetic (OKN) reflex in head-fixed pigeons. We analyzed these responses in
      two behavioral conditions: (1) animals were hung in a harness ("resting"
      condition); and (2) animals were additionally submitted to a frontal airflow that
      provoked a flight posture ("flying" condition). In both conditions, cervical
      stimulation provoked a slow phase of very low gain (around 0.05) in the opposite
      direction to that of the stimulation and fast phases triggered near the head-body
      alignment in the same direction as the stimulation. The slow phase showed a phase
      lag of 20 deg at 0.5 Hz. The gain of the slow phase was not modified by the
      velocity, amplitude, or frequency of the stimuli. This gain was not changed by
      the presence of a fixed visual surround. When cervical stimuli (0.05-0.5 Hz) were
      added to an optokinetic stimulation (30 deg/s) in the "resting" condition, the
      slow phase velocity (SPV) of the optokinetic reflex was modulated with a time
      course close to that produced by the cervico-ocular reflex alone. The SPV was
      alternately increased and decreased round the SPV level corresponding to the
      steady-state OKN. In the "flying" condition, optokinetic-cervical stimulation
      provoked an eye beating field and a strong SPV modulation synchronized with the
      position of the cervical stimulation. The number of nystagmic beats (OKN) and the
      amplitude and velocity of the fast phases were modulated in correlation with the
      SPV. Consequently, the optokinetic response was increased or decreased according
      to whether the cervical stimuli were in the reverse direction or in the same
      direction as the optokinetic stimulation, respectively. These data are
      interpreted as an improvement of gaze stabilization by the COR. This mechanism is
      context dependent, since it is strongly reinforced during the flight.

PMID- 15259569
TI  - All amacrine cells in the rabbit retina possess AMPA-, NMDA-, GABA-, and glycine
      activated currents.
AB  - Physiological properties of ligand-activated currents were characterized for
      morphologically identified AII amacrine cells in the rabbit retina by using whole
      cell recordings in a superfused retina slice preparation. The AII amacrine cells
      were identified based on their distinct narrow-field, bistratified morphology. In
      the present study, the whole-cell recordings from AII amacrine cells synaptically
      isolated from presynaptic influences demonstrated the presence of glutamate AMPA
      (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors, but no
      kainate receptors. The presence of only AMPA receptors on rabbit AII amacrine
      cells is in contrast to an earlier study on rabbit AII amacrine cells by
      Bloomfield and Xin (2000), but consistent with previous studies on rat AII
      amacrine cells. In addition, NMDA (N-methyl-D-aspartate) -activated currents
      blocked by the NMDA antagonist D-AP7 (D-2-amino-7-phosphonoheptanoic acid) were
      found on the AII amacrine cells. These most likely extrasynaptic NMDA-activated
      currents were attenuated by the presence of Co2+ interacting with Mg2+ and Ca2+
      as they competed for divalent cation-binding sites within the NMDA channel. AII
      amacrine cells also possessed GABA (gamma-aminobutyric acid) -activated currents
      that were unaffected by the GABAc receptor antagonist TPMPA (1,2,5,6
      tetrahydropyridine-4-yl methylphosphinic), but were completely blocked by the
      GABA(A) antagonist bicuculline. This indicates that the major inhibitory inputs
      were mediated by only GABA(A) receptors located directly on the AII amacrine
      cells. Furthermore, although the AII amacrine cells were glycinergic amacrine
      cells, they also possessed glycine-activated currents that may be mediated by
      autoreceptors.

PMID- 15259570
TI  - Phonetic and phonological perspectives on speech production in cleft lip and
      palate.

PMID- 15259571
TI  - Is presurgery and early postsurgery performance related to speech and language
      outcomes at 3 years of age for children with cleft palate?
AB  - This study examined the relationship between presurgery speech measures and
      speech and language performance at 39 months as well as the relationship between
      early postsurgery speech measures and speech and language performance at 39
      months of age. Fifteen children with cleft lip and palate participated in the
      study. Spontaneous speech samples were obtained in the children's homes at
      presurgery/ 9 months, postsurgery/13 months and again at 39 months of age.
      Correlational analyses revealed a lack of association between speech measures
      presurgery and early postsurgery and speech outcome measures at 39 months.
      Significant negative correlations were noted for true canonical babbling ratio
      presurgery and mean length of utterance (MLU) at 39 months, as well as for size
      of true consonant inventory presurgery, and both language outcome measures at 39
      months (MLU and number of different words). Significant positive correlations
      were noted for percentage of true stops produced postsurgery and both language
      measures at 39 months. Variables that may have influenced speech and language
      development from presurgery to 39 months are discussed.

PMID- 15259572
TI  - The impact of early infant jaw-orthopaedics on early speech production in
      toddlers with unilateral cleft lip and palate.
AB  - The purpose of study was to investigate the impact of pre-surgical Infant
      Orthopaedics (IO) on consonant production at 18 months of age in children with
      Unilateral Cleft Lip and Palate (UCLP) and to compare the consonant production to
      that of age-matched children without clefts. The first ten children in a
      consecutive series of 20 with UCLP received IO and the following ten did not.
      Both groups had soft palate repair at 6.3 months of age. The cleft in the hard
      palate was unrepaired. Ten normally developing children without clefts served as
      controls. Nine children in each group accomplished the study. Phonetic
      transcriptions of consonants were made from audiotape recordings obtained during
      a 45-60 minute interactive session. No significant differences in the number of
      consonant tokens or of consonant types were found between the UCLP children with
      and without IO but both groups had significantly lower numbers than the control
      group. There was no significant difference in frequency of different manners or
      places of articulation of plosives between the UCLP groups. The frequency of
      occurrence of bilabial and dental consonant placements of plosives were
      significantly higher in the control group than in both UCLP groups.

PMID- 15259573
TI  - Abnormal patterns of tongue-palate contact in the speech of individuals with
      cleft palate.
AB  - Individuals with cleft palate, even those with adequate velopharyngeal function,
      are at high risk for disordered lingual articulation. This article attempts to
      summarize current knowledge of abnormal tongue-palate contact patterns derived
      from electropalatographic (EPG) data in speakers with cleft palate. These data,
      which have been reported in 23 articles published over the past 20 years, have
      added significantly to our knowledge about cleft palate speech. Eight abnormal
      patterns of tongue-palate contact are described and illustrated with data from
      children and adults with repaired cleft palate. The paper also discusses some of
      the problems in interpreting EPG data from speakers with abnormal craniofacial
      anatomy and emphasizes the importance of quantifying relevant aspects of tongue
      palate contact data. Areas of research requiring further investigation are
      outlined.

PMID- 15259574
TI  - Compensatory articulatory behaviours in adolescents with cleft palate: comparing
      the perceptual and instrumental evidence.
AB  - A combination of perceptual and electropalatographic (EPG) analysis is used to
      investigate speech production in three adolescent speakers with a history of
      cleft palate. All the subjects still sound markedly atypical. Their speech output
      is analysed in three conditions: diadochokinetic tasks; single word production;
      connected speech. Comparison of the EPG and perceptual data reveals important
      lingual behaviours which were not identified by perceptual analysis alone.
      Lingualpalatal contact patterns previously noted in the speech of younger
      speakers with cleft palate are identified, as well as some lingual behaviours not
      previously reported in the literature. Similarities and differences between the
      individual speakers' profiles are discussed, as is the considerable inter- and
      intra-speaker variability identified in the data, and the speech output is
      discussed with reference to the notion of compensatory articulation.

PMID- 15259575
TI  - Single-word intelligibility in speakers with repaired cleft palate.
AB  - Many speakers with repaired cleft palate have reduced intelligibility, but there
      are limitations with current procedures for assessing intelligibility. The aim of
      this study was to construct a single-word intelligibility test for speakers with
      cleft palate. The test used a multiple-choice identification format, and was
      based on phonetic contrasts which are problematic for speakers with cleft palate.
      Fifteen Cantonese speakers with repaired cleft palate served as speakers. The
      intelligibility score of each speaker was calculated, based on the number of
      words correctly identified by eight naive listeners. The most problematic
      contrasts, based on mean error proportions, were place of articulation (stops and
      nasals), stop versus fricative, and stop versus affricate. The most robust
      contrasts were also determined, and physiological and language-specific
      interpretations offered. Single-word intelligibility could be predicted with 91%
      accuracy using three phonetic contrasts. The importance of an 'explanatory'
      intelligibility test, for focusing treatment and monitoring severity, is
      discussed.

PMID- 15259576
TI  - Laparoscopic intragastric resection of gastric stromal tumor located at the
      esophago-cardiac junction.
AB  - We performed laparoscopic intragastric surgery (LIGS) for gastric stromal tumors
      located at the esophago-cardiac junction (ECJ) in 7 patients. The tumors measured
      27 to 75 mm in diameters. Histologically, there were 4 cases of gastrointestinal
      stromal tumors, 2 leiomyomas, and 1 schwannoma. LIGS was performed with 1 camera
      port (10 mm) inserted by the open method and two 5-mm working ports inserted by
      puncturing the stomach. Tumors were enucleated or resected with appropriate
      margins confirming the muscle layer of the stomach wall and retrieved orally by
      gastrofiberscope. The mean surgical duration was 141.4 minutes. Recent patients
      took their first meal on day 3 postoperatively and were discharged within a week.
      There were no complications including stenosis or gastroesophageal reflux in any
      patient to date. LIGS is a feasible surgical option for gastric stromal tumors
      located at ECJ.

PMID- 15259577
TI  - Long-term complications of laparoscopic ventral and incisional hernia repair.
AB  - To date, there have been no long-term follow-up studies of the results of
      laparoscopic ventral and incisional hernia repair. We evaluated the long-term
      complications of these repairs over a mean follow-up period of 64 months. Between
      March 1993 and April 2000, we retrospectively evaluated 9 patients who underwent
      ventral or incisional hernia repair with prosthetic material and one patient who
      received laparoscopic primary closure of a hernia defect. The prosthetic material
      polypropylene was used in one patient and an expanded-polytetrafluoroethylene
      patch was used in the other 8. In one patient, the hernia was closed directly. In
      7 patients, the prosthesis was fixed by stapling or tacking with no transfacial
      suture fixation and a 2-cm prosthesis overlap. In 2 later patients, we modified
      our technique by fixing the prosthesis by stapling or tacking with transfacial
      suture fixation and using prosthesis overlap of more than 3 cm. There were 2
      episodes of hernia recurrence (20%), one of which required reoperation. Both
      occurred in patients in whom we used the unmodified repair technique. One of the
      patients in whom we used the unmodified technique developed a seroma which
      resolved spontaneously without antibiotic therapy. One patient in whom we used
      the modified technique developed infection (10%) requiring removal of the
      prosthetic material. The 2 episodes of hernia recurrence occurred 40 months after
      laparoscopic treatment, and the case of infection occurred 11 months after
      treatment. There were no episodes of recurrence in patients who received the
      unmodified surgery and had hernia defects less than 42 cm2. To perform safe and
      effective laparoscopic repair of ventral or incisional hernias, it is necessary
      to use a prosthetic overlap of more than 3 cm from the edge of the hernia gate
      and to use transfacial suture fixation with nonabsorbable sutures. In addition,
      patients who undergo laparoscopic ventral or incisional hernia repair should be
      observed for more than 5 years.

PMID- 15259578
TI  - Abandoned endoscopic procedures.
AB  - Intraoperatively, it may be prudent at times to abandon or defer the intended
      therapeutic procedure due to adverse prevailing conditions. A decision to abandon
      or defer an endoscopic procedure would necessarily result in less morbidity
      compared with conventional open surgery. A retrospective review of endoscopic
      procedures that were abandoned or deferred and subsequent patient outcomes were
      noted. Between January 1998 to May 2003, 48 procedures out of a total of 11,550
      endoscopic surgical procedures had to be abandoned. Previously unsuspected
      intraabdominal malignancy was the cause in 32 patients. Anesthesia-related
      problems led to the decision in 6 patients. Coincidental tuberculosis and failure
      in accessing the target organ were the cause in two patients each. An ectopic
      gallbladder, an absent gallbladder, a pancreatic phlegmon, and a failure to
      achieve proper single-lung ventilation led to the decision in one patient each.
      In two patients, presence of dense intraabdominal adhesions that precluded
      further progress led the surgeon to abandon the surgery. The patients with
      intraabdominal malignancy were staged for their disease and treated accordingly.
      Nine patients without malignancy who had their operation deferred due to diverse
      reasons were operated on a later date, whereas 4 patients were lost to follow-up.
      The 9 patients who underwent operation at a later date are well on follow-up.
      Four patients with intraabdominal malignancy died, whereas the others are well in
      follow-up after being treated according to the stage of their disease. Certain
      adverse situation encountered intraoperatively may lead the surgeon to change the
      approach to surgery and abandon the procedure. He may consider operation at a
      suitable time later or consider a different treatment altogether. The morbidity
      consequent to such a decision is much less if the operative approach is an
      endoscopic one.

PMID- 15259579
TI  - Video-assisted open thyroid lobectomy through a small incision.
AB  - To examine if postoperative morbidity may occur in gasless video-assisted thyroid
      lobectomy, 111 patients with solitary nodules were treated either by gasless
      video-assisted lobectomy or by conventional lobectomy. Operating time needed for
      video-assisted lobectomy significantly exceeded that needed for conventional
      surgery. No death, massive hemorrhage, wound hematoma, wound infection, or
      permanent recurrent laryngeal nerve injury occurred in patients treated by either
      video-assisted or conventional lobectomy. Damage to the external branch of the
      superior laryngeal nerve occurred in 6 (10.2%) patients following conventional
      surgery but in no patients following video-assisted lobectomy (P = .0289).
      Transient recurrent laryngeal nerve palsy occurred in 5 (8.5%) patients after
      conventional surgery and in 3 (5.8%) patients after video-assisted surgery (P =
      .7209). It is noteworthy that morbidity occurs in video-assisted lobectomy. The
      general principles of thyroid surgery should be followed to avoid the occurrence
      of complications.

PMID- 15259580
TI  - Mediastinal neurogenic tumors and video-assisted thoracoscopy: always the right
      choice?
AB  - Neurogenic mediastinal tumors in adults are generally benign lesions and for this
      reason are ideal candidates for resection by video-assisted thoracoscopy (VAT).
      Usual contraindications to VAT are the dimension of the tumor (greater than 6
      cm), its position (apex, posterior costodiaphragmatic angle), and/or the presence
      of intraspinal growth (the so-called "dumbbell tumors"). This study reviewed a
      single-institution 10-year experience approaching mediastinal neurogenic tumors
      routinely by VAT, even in cases of the above mentioned contraindications. From
      January 1992 to December 2002, 15 consecutive mediastinal neurogenic tumors were
      operated by VAT (11 females, mean age 43 years, range 16-67). Mean operating time
      was 99 minutes (range 60-180). No conversion thoracotomy was required. The 2
      cases of "dumbbell tumor" in this series were treated by laminectomy followed by
      VAT. Two patients had a Claude-Bernard-Horner syndrome after removal of lesion at
      the level of T1-T2. Mean postoperative stay was 5.5 days. Histologic diagnosis
      was schwannoma in 12 cases (Antoni type A in 7 cases, type B in 4 cases, mixed
      type in 1 case) and neurofibroma in 3 cases. Results from this 10-year experience
      confirmed that VAT can be the standard approach for neurogenic tumors in adults
      without negative effect on radicality of resection and safety of the procedure.

PMID- 15259581
TI  - Exposure of splenic hilum increases safety of laparoscopic splenectomy.
AB  - Laparoscopic splenectomy is becoming the gold standard technique for the
      treatment of hematological disorders of the spleen. Hemostasis is a fundamental
      step during laparoscopic splenectomy leading some authors to develop several
      techniques to control splenic vessels such as hand assistance, preoperative
      splenic artery embolization, and the use of vascular linear staplers. However,
      intraoperative bleeding is usually due to inadequate exposure of the hilar
      splenic vessels itself. The authors describe a standardized technique for the
      exposure of splenic pedicle using an endoscopic triangular retractor. We have
      been used this technique in 16 consecutive laparoscopic splenectomies with
      minimal blood loss. The present technique may increase the safety of laparoscopic
      splenectomy with adequate exposure of the splenic hilum reducing the conversion
      rate and intraoperative blood loss.

PMID- 15259582
TI  - Ectopic gallbladder: laparoscopic cholecystectomy.
AB  - An unusual case of ectopic retroplaced gall bladder is reported. In our patient,
      this congenital anomaly was detected on ultrasonography and confirmed by CT scan,
      MRCP, and ERCP. Laparoscopic cholecystectomy was performed without complications.
      The importance of proper preoperative investigations is emphasized for accurate
      diagnosis, to rule out biliary tract anomalies, and to properly plan surgical
      approach and management.

PMID- 15259583
TI  - Laparoscopic colectomy for obstructing sigmoid cancer with prior insertion of an
      expandable metallic stent.
AB  - We report a patient with obstructing cancer of the sigmoid colon initially
      treated with a self-expanding metallic stent. The metallic stent successfully
      relieved the intestinal obstruction, and laparoscopic anterior resection was
      performed subsequently. The use of this approach in the management of patients
      with obstructing colorectal cancer is discussed.

PMID- 15259584
TI  - Laparoscopic suture rectopexy for rectal prolapse in a 22-month-old child.
AB  - We present the case of a 22-month-old female child who presented with severe
      recurrent rectum prolapse. The patient was successfully managed using the
      laparoscopic simple suture rectopexy approach with 5-mm instruments employing two
      3-0 nonabsorbable sutures on either side of the rectum to secure it to the
      presacral fascia. There was no blood loss, and the procedure was completed
      without complication. The child was followed up for a period of 24 months with
      good results.

PMID- 15259585
TI  - Bilateral endoscopic adrenalectomy for Cushing's syndrome in a patient with
      polycystic liver and kidney disease.
AB  - Microadenomectomy via a transsphenoidal approach is today's treatment of choice
      to achieve normal cortisol blood levels in patients with ACTH-secreting pituitary
      tumors. Should neurosurgery fail, bilateral adrenalectomy is recommended. Today
      the endoscopic, transabdominal or retroperitoneal adrenalectomy is regarded as
      the gold standard for the operation of endocrine-active adrenal tumors.
      Therefore, in principle, the question of the indication for the endoscopic
      operation no longer arises but only the question of the technical feasibility in
      individual cases. We report on a patient with a pituitary-dependent Cushing's
      syndrome after a twice-repeated unsuccessful transsphenoidal adenomectomy and
      with additional polycystic kidney and liver disease, who underwent bilateral
      retroperitoneoscopic adrenalectomy. Despite the massive enlargement of both
      kidneys, it was possible to safely perform a bilateral retroperitoneoscopic
      adrenalectomy. In the case of marked bilateral cystic kidneys, a bilateral
      retroperitoneoscopic adrenalectomy in Cushing's syndrome is technical possible
      and a safe and effective method of treatment.

PMID- 15259586
TI  - The da Vinci robot in right adrenalectomy: considerations on technique.
AB  - The da Vinci Robotic System (Intuitive Surgical, Mountain View, CA) became
      available at the General Surgery Department of Camposampiero Hospital in May
      2001. From May 2001 to October 2002, 139 robotic operations were performed, one
      of which was a right adrenalectomy for a right adrenal mass. The progressive
      growth of the mass was the indication for surgical excision. Surgical
      adrenalectomy was successfully completed with da Vinci Robotic System using 5
      ports (3 for the robotic system, 2 as service trocars). The wrist-like movements
      of the instrument's tip easily enabled the detachment of the right hepatic lobe
      from the gland and vessel isolation, while the 3-dimensional vision facilitated
      dissection of the veins from the vena cava.

PMID- 15259587
TI  - Laparoscopic management of antenatally-diagnosed abdominal cysts in newborns.
AB  - We report two newborns each detected to have a large intra-abdominal cyst on
      antenatal ultrasonography. Postnatal imaging confirmed presence of the cysts and
      showed a complex cyst with multiple septae in the first patient and evidence of
      bleeding in both. Laparoscopy performed on the 14th and 19th day of life,
      respectively, showed ovarian cysts with hemorrhage and torsion. The cysts were
      treated successfully by laparoscopic oopherectomy. Histopathology revealed an
      ovarian gonadoblastoma in the first patient and a simple cyst with calcification
      in the second. Both patients remain well at a follow up of six and four months.
      Laparoscopic treatment of antenatally detected cystic abdominal masses is a
      feasible option in the newborn.

PMID- 15259588
TI  - Howard Kelly's minimally invasive autopsy circa 1882.

PMID- 15259589
TI  - Increased gallbladder trypsin in acute cholecystitis indicates functional
      disorder in the sphincter of Oddi and could make EPT a logical procedure.

PMID- 15259590
TI  - Genetic determinants: is there an "atherosclerosis gene"?
AB  - It is now clear that atherosclerotic disease is a chronic inflammatory disease
      triggered by a sequence of events initiated at sites with turbulent flow under
      normal conditions such as in the coronary arteries or at bifurcations or where
      normal laminar flow is replaced by turbulent flow because of vessel pathologies.
      Normally, laminar flow is protected by generation of NO by endothelial NO
      synthase (eNOS), which becomes activated via stretch activated channels. When the
      flow turns turbulent, such protective NO generation ceases, leading to
      endothelial cell activation and lipid deposition into the extra-cellular space.
      There, lipoproteins and specifically phospholipids become oxidized by cells of
      the monocytic-macrophage lineage. Only when the LDL-cholesterol level is high
      enough lipid peroxidation products are generated in sufficient amounts to
      perpetuate the disease by generating a feed forward loop of endothelial cell
      activation leading to an inflammatory response. That inflammatory response might
      also be added by bacterial or viral infections such as Chlamydia pneumoniae or
      viruses. The disease then progresses to a chronic inflammatory state, whereby the
      immune system seems to contribute significantly and markers of chronic
      inflammation such as fibrinogen, leukocytes, PAI-1 and CRP are found increased.

PMID- 15259591
TI  - Periodic fever syndromes--a clinical overview.
AB  - Most hereditary periodic fever syndromes known today have their onset in the
      first year of life. Only two, namely Familial Mediterranean Fever (FMF) and TNF
      Receptor Associated Periodic Syndrome (TRAPS) occur later, with most patients
      having become symptomatic by their twentieth birthday. Therefore this review will
      concentrate on FMF and TRAPS, the latter being a very rare disease, while the
      former has become somewhat more common in mid-Europe as a result of migration.

PMID- 15259592
TI  - [Natural therapy instead of chemistry? Probiotics in gastroenterology].
AB  - Probiotics are living microorganisms that upon ingestion exert health benefits.
      The impact of probiotics on gut flora represents a new and interesting
      therapeutic approach in a number of diseases of the gastrointestinal tract.
      According to actual publications and guidelines of medical societies, the
      clinical relevance of probiotics can be described as follows: (a) In the case of
      ulcerative colitis, available data demonstrate benefits of probiotic therapy. (b)
      The available data regarding pouchitis are limited, but the therapeutic effect
      seems to be excellent. (c) In the case of Crohn's disease, the role of probiotics
      is not clearly defined, thus the results of new trials have to be awaited before
      probiotic therapy is recommended. (d) Further indications such as antibiotic
      associated diarrhea, acute pancreatitis or irritable bowel syndrome have been
      reported recently. The results of these clinical trials have been encouraging,
      but they often included only a small number of patients and therefore a clear-cut
      assessment seems difficult at the moment.

PMID- 15259593
TI  - [On the involvement of the temporomandibular joint in rheumatoid arthritis].
AB  - 64 patients with rheumatoid arthritis (RA) were examined for temporomandibular
      joint (TMJ) symptoms as well as for the severity and incidence of their symptoms.
      In detailed interviews, a total of 34 patients (53.1%) reported TMJ symptoms, the
      main complaints being problems during opening and closing of the mouth (45.2%).
      RA patients with TMJ symptoms differed significantly from those without TMJ
      symptoms (p < 0.01) in the duration (121.7 +/- 100.5 months vs. 37.1 +/- 27.6
      months) and the state of activity of the basic disease. The patients subjectively
      evaluated the severity of the TMJ symptoms as mild to moderate (grade: 2-3;
      severity: 241 +/- 1.01). Almost 70% reported occasional symptoms, 22.5% frequent
      symptoms and 10.6% permanent symptoms (p < 0.01). 61.8% (21/34) of the patients
      showed no radiographic change in the shape of the TMJ condyle, whereas 11.8%
      (4/34) demonstrated a change on one side an 26.4% (9/34) a change on both sides.
      There was no difference in the severity of the TMJ symptoms between patients with
      an unchanged condyle (n = 21; severity: 2.33 +/- 0.96) and patients with changes
      in condylar shape (n = 13; severity: 2.5 +/- 1.12). A frequent involvement of the
      temporomandibular joint in RA can be considered certain. The symptoms, which were
      generally moderate, can cause a marked impairment of daily used functions, such
      as chewing and speaking.

PMID- 15259594
TI  - Microalbuminuria: prevalence in hypertensives and diabetics.
AB  - BACKGROUND: Microalbuminuria is the mild elevation of urinary albumin excretion
      and reflects the progression of clinical nephropathy and cardiovascular disease
      and mortality risks of diabetic and hypertensive patients. The aim of this study
      was to determine the prevalence of and risk factors for microalbuminuria amongst
      Turkish people who had diabetes and/or hypertension and were older than 35 years
      of age. METHODS: In this cross-sectional study, from a pool of 7708 people over
      35 years of age living in the Park Health Centre Area of Ankara, Turkey, we
      randomly selected 550 out of 926 hypertensive and/or diabetic patients. The area
      is also the research district of Ankara University Medical Faculty's Public
      Health Department. The results of 493 of those examined for microalbuminuria are
      represented in the study. An immunospecific dipstick Micral Test II was used for
      microalbuminuria screening and Medi-test urinary strip for macroalbuminuria.
      Additionally, blood pressure levels were recorded, fasting blood glucose levels
      were measured by Glucotrend and questionnaire forms were filled out. Chi square
      and logistic regression analyses were used for statistical analyses. RESULTS: In
      the study population, 439 patients were hypertensive, 194 patients were diabetic
      and of these, 140 were both hypertensive and diabetic. Overall prevalence of
      microalbuminuria was 19.1% and macroalbuminuria was 4.4% in the study group.
      Microalbuminuria prevalence was 18.9% in the hypertensive group and 21.7% in the
      diabetic group. In the hypertensive group, diastolic pressure level, male sex and
      type of accommodation, in the diabetic group, duration of diabetes, fasting blood
      glucose levels and type of accommodation were all influential factors for
      microalbuminuria according to the results of the multiple logistic regression
      analyses. CONCLUSION: Our study shows a high prevalence of microalbuminuria in
      both hypertensive and diabetic patients, males being at Special risk. Lowering of
      diastolic blood pressure and amelioration of living Standards should be the first
      goal of treatment according to our results.

PMID- 15259595
TI  - [Panic disorder and angina pectoris].
AB  - Panic attacks are a frequently cited cause of noncardiac chest pain. A strict
      separation of the internist's job (i. e., ruling out an "organic" cause of the
      patient's complaints) from the psychiatrist's job (e. g., diagnosing and treating
      panic disorder if present) may not always be the most efficient way of diagnostic
      work-up. We present the case of a 56-year-old female referred to our institution
      for elective coronary arteriography. Significant cardiovascular risk factors and
      symptoms compatible with unstable angina illustrate the common problem of a high
      probability of cardiac pathology in a patient with possible psychiatric symptoms.
      A modified SCID-interview complementing the coronary angiography results finally
      led to the definite diagnosis in this patient after symptoms had been present for
      over 20 years.

PMID- 15259596
TI  - Fungal toxicity with special reference to mycotoxins.
AB  - Mycotoxins are fungal secondary metabolites formed by consecutive series of
      enzyme-catalysed reactions from a few biochemically simple intermediates of
      primary metabolism. These mycotoxins can enter the human and animal food chain by
      direct or indirect contamination. Mycotoxins are equally harmful to animal and
      human beings. Realizing the importance of mycotoxins to the health of man and
      animals there have been concentrated efforts to develop highly sensitive
      analytical methods for detection and proper determination of mycotoxins in food,
      mixed feeds and feed ingredients, animal tissue, blood, urine and milk. Most of
      the mycotoxins are identified and most current research on it is concentrated on
      increasing sensitivity accuracy and reproducibility and above all to decrease the
      time of determination. A detailed review of mycotoxin and their detection is
      summarised in the paper.

PMID- 15259597
TI  - Impact of urbanization on Bellandur Lake, Bangalore--a case study.
AB  - Lake and river water is the prime source for drinking, irrigation and other
      domestic purposes. Bellandur Lake is one of the major Lakes of Bangalore city.
      The addition of effluents from urbanized Bangalore city has changed the
      characteristics of the Lake from being a natural ecologically healthy Lake to an
      artificial reservoir of domestic sewage and industrial effluents. The DO of the
      Bellandur Lake water ranged from 3.8-6.3 mg/l. The Bellandur lake water BOD
      ranged from 89-99 mg/l due to absorption of pollutants by aquatic flora in lake
      system. If the present state of affairs continues for long, the Bellandur Lake
      may soon become an ecologically inactive Lake.

PMID- 15259598
TI  - Determination of a limiting nutrient regulating algal biomass using in situ
      experiments of nutrient enrichment bioassay (NEB) and empirical relations of
      nutrients and chlorophyll-a.
AB  - Long-term nutrient contents and nutrient ratios indicated that phosphorus was a
      potential limiting element for algal growth. In situ experiments of nutrient
      enrichment bioassay supported the evidence of P-limitation. However, regression
      analyses of log10-transformed chlorophyll-a (CHL) against TP (R2 values < 0.25)
      showed that seasonal CHL was not closely related to flux of phosphorus during all
      seasons. Also, two dimensional graphical approach of Trophic State Index (TSI)
      showed that most values of TSI (CHL) -TSI (TP) and TSI (CHL) -TSI (SD) were less
      than zero, indicating factors other than phosphorus limited algal biomass (CHL 
      TP < 0), and that non-algal particles dominated light attenuation (CHL -SD < 0).
      The weak empirical relations and trophic deviations were explained well by the
      experiment of NEB-II that was conduced during a period of high inorganic
      turbidity. Overall results suggest that phosphorus is the primary element
      regulating the system productivity, but the system also were highly influenced by
      rapid flushing and high inorganic turbidity.

PMID- 15259599
TI  - Identification of ecologically significant habitats for urban nature
      conservation: a case study in Turkey.
AB  - Given the rapid urbanization of Turkey, sustained productivity of natural
      resources should be an integral part of any urban development policy. The
      biogeochemical cycles and ecosystem services link urban and rural ecosystems. It
      is, therefore, essential that ecologically significant habitats along urban-rural
      continuum be protected to secure public and environmental health. This
      necessitates their identification and the establishment of administrative and
      legal foundations for urban nature conservation in the management of urban
      habitats, should be established Ecological analysis of urban habitats of
      Karsiyaka led to the identification of 19 ecologically significant habitats.
      Nature conservation priority was rated, using rarity, species richness,
      stratification, site age, and area of the habitats. Ecologically significant
      habitats made up about 54 ha of the total urban green space of 289 ha in
      Karsiyaka. The total number of plant species was estimated to be 273.

PMID- 15259600
TI  - Characterization of alkaline phosphatases of some potent phosphate removers.

PMID- 15259601
TI  - Bioaccumulation of fenvalerate technical grade in different organs of the frog
      Haplobatrachus tigerinus (Daudin).
AB  - Bioaccumulation studies of fenvalerate were conducted on Indian bullfrog
      Haplobatrachus tigrinus (Daudin) after exposure to sublethal intraperitoneal dose
      of technical grade fenvalerate (1/3 LD50 i.e. 116.66 microg/kg body weight) at 3,
      6, 12, 24, 48 and 72 hours schedule. The tissues viz., muscle, liver, kidney,
      testis, brain, and whole body accumulation was analysed for residue estimations.
      In all the tissues, analysed maximum residue was recovered in the initial stages
      of exposure (3 and 6 hours). However, in brain the residues remained up to 72
      hours. In the whole body, analysis after 3 hours of exposure 78.65% residue was
      recovered and by the time 72 hours passed only, 9.4% residue was recovered. The
      decline in residue levels along with the period of exposure indicates the fast
      acting nature of fenvalerate and metabolites.

PMID- 15259602
TI  - Ultra-structural observations on the lymphoid organs of the freshwater catfish,
      Clarias batrachus (Linnaeus).
AB  - Light microscopic and ultra-structural studies of the lymphoid tissues such as
      blood immunocytes, spleen and pronephros of the freshwater catfish, Clarias
      batrachus, were carried out. The peripheral blood showed nucleated erythrocytes,
      total leucocytic count (TLC) more than that observed in mammalian blood and
      leucocytes with morphological appearance similar to the mammalian white blood
      cells (WBCs). The spleen and pronephros showed presence of numerous lymphocytes,
      monocytes and nucleated red blood cells (RBCs) along with hemosiderin-containing
      macrophages. The morphology of lymphoid organs of the catfish has been discussed
      in light of the evolution of the immune system in this class of vertebrates.

PMID- 15259603
TI  - The effect of lead bioaccumulation on haem biosynthetic enzymes in fish.
AB  - The bioaccumulations of lead in the liver and hepatic microsomes of fish after 1,
      3, 7, 14, 28, and 45 days exposure were studied. In addition, the relationship
      between the bioaccumulated lead in both hepatic microsomes and the liver and
      their haem biosynthetic enzymes were studied. Lead toxicity was shown to result
      in a depression of the microsomal mixed function oxidase system, as assessed by a
      decrease in hepatic microsomal cytochrome P-450 and b5 content and by a decrease
      in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase.
      Lead had a more marked effect on cytochrome P-450 than b5. The activity of the
      rate-limiting enzyme of haem biosynthesis, delta-aminolevulinic acid synthase,
      was inversely correlated with the microsomal cytochrome P-450 content. The
      activity of the heam biosynthetic enzymes delta-aminolevulinic acid dehydratase,
      coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead
      pretreatment. The activity of the haem catabolic enzyme, haem oxygenase, was
      increased by concentration and length of time to lead exposure.

PMID- 15259604
TI  - Research of usability of tree leaves and soil in determining the contribution of
      industry and traffic to air pollution in Bozuyuk (Turkey) region.
AB  - In industrialized regions like Bozuyuk, generally density of settlement and
      traffic is also observed. As a result of this density, the metal pollution that
      results from either industrial activities or traffic shall affect the air quality
      negatively. In determining this effect and sources thereof inspection of the
      depositing of heavy metals, which cause pollution, on the tree leaves and in the
      soil, and making comments by comparing with the values in the same kinds of
      plants and soil in the clean region has been aimed. For this purpose, zinc,
      copper, chromium, cadmium, iron, nickel, lead analysis have been carried out in
      order to determine the accumulation of pollution in plants and soils resulting
      from heavy industry and vehicles around Bozuyuk (Turkey) region which is close to
      highway. These analyses have been carried out on washed and unwashed tree leave
      samples and surface soil from ten locations. Data used in the results were the
      average values of a series of data obtained from the experimental studies.

PMID- 15259605
TI  - Effect of kinetin on leaf protein content and its profile in mung bean under salt
      stress.
AB  - Application of NaCl resulted in about 67% reduction in amino acid content and 24%
      reduction in buffer soluble protein content in mung bean [Vigna radiata (L.)
      Wilczek.] leaf as compared with the control. Gel electrophoretic profile of
      buffer soluble protein content in leaf of mung bean showed an extra band in
      between 29 kD and 45 kD in stress protein profile as compared with control. It
      was noted that the foliar spray of kinetin (6-furfuryl aminopurine) used in the
      present study was able to overcome up to certain extent the adverse effects of
      stress caused by NaCl.

PMID- 15259606
TI  - Autecology of the tailed jay butterfly Graphium agamemnon (Lepidoptera :
      Rhopalocera : Papilionidae).
AB  - The Tailed Jay Graphium agamemnon is one of the attractive papilionid butterflies
      that enliven the environment of Visakhapatnam. It occurs throughout the year. It
      lays eggs singly on young leaves of the mast tree Polyalthia longifolia var.
      pendula (Annonaceae). The eggs take 3-4 days to hatch. The larvae go through 5
      instars over a period of 15-16 days. The pupal period is 13-14 days. The total
      period from egg to adult emergence spans over 33-36 days. Based on this short
      life cycle, and larval and pupal development success studied every month, this
      butterfly can be multivoltine with a minimum of 7-8 broods in a year. Both CI and
      GR decreased with the age of larva, their average figures being 3.78 and 0.43
      respectively. AD values are high (average 92%) and decreased through successive
      instars. Both ECD and ECI followed a similar pattern with an increase from instar
      I up to II, then a decrease up to IV and again an increase in instar V and the
      highest value is with fifth instar. Adults frequently visited flowers (12-35
      flowers in a min) spending 1.0 to 3.2 seconds on a flower. The nectar
      concentration ranged between 16 and 58%. Peak foraging activity mostly fell
      between 0900-1000 h. The proboscis received pollen in most of the floral species
      visited, thus satisfying one of the characteristics of butterfly pollination.
      Being a fast and strong flier it is treated as "high energy" pollinator promoting
      cross-pollination.

PMID- 15259607
TI  - Hepato and nephrotoxicity in rat exposed to endosulfan.
AB  - The indiscriminate and injudicious use of pesticides particularly endosulfan in
      agriculture and animal husbandry practices has considerably increased the risk of
      human health hazard. The present work was therefore undertaken to evaluate the
      toxic effect of endosulfan on the vital organs viz. liver and kidney of rat. Oral
      administration of endosulfan at the dose level of 10 mg/kg b.wt./day for two and
      four weeks showed toxic interference with the biochemistry and histology of rat
      liver and kidney. The biochemical parameters viz. Aspartate amino transferase,
      alanine amino transferase, acid phosphatase, alkaline phosphatase, bilirubin urea
      and creatinine were increased which clearly showed the hepato and nephrotoxic
      effect of endosulfan. Histopathologically the size of liver was increased,
      sinusoidal dilation, pyknotic nuclei, cytoplasmic degranulation and various
      nuclear aberrations were observed. Similarly pathological alterations viz.
      chronic glomerulonephritis, glomerulosclerosis, odenoma and glomerulus deposits
      were observed in the kidney.

PMID- 15259608
TI  - Physicochemical and microbiological assessment of Oko-oba--a Nigerian abattoir.
AB  - The physicochemical and microbiological assessments of Oko-oba abattoir were
      carried out during dry and wet season to determine whether the waste discharges
      are within tolerable limits. All the physicochemical parameters studied showed
      seasonal variations. Higher temperature and lower pH values were recorded during
      the dry season than wet season. Similarly, the BOD of wastewater from the slab
      decreases from 10000 mg/ml during the dry season to 6000 mg/ml in the wet season.
      Conversely, the BOD of the final waste discharge was 4000 mg/ml during the dry
      season and 3,500 mg/ml during the wet season. The COD showed similar trend, with
      values ranging from 12,200 to 18,500 mg/ml depending on the season. The suspended
      solid values ranged from 1200 to 1950 mg/ml. The phosphate and nitrate ions were
      in the range of 41-75 mg/l and 22.5- 960 mg/ml respectively. Heavy metals
      detected were Chromium at 104 -114 mg/ml, Copper 16 -75 mg/ml and Iron 55- 114
      mg/ml. The following bacteria species were also encountered: B. cereus, E. coli,
      P. aeruginosa, S. aureus, S. faecalis, S. lactis, Micrococcus sp, A. aerogenes,
      P. vulgaris, and S. typhi. The results showed significantly high level of
      pollutants in the waste discharged.

PMID- 15259609
TI  - Effects of farmyard manure and chemical fertilizers on the nutritional status of
      the loquat trees.
AB  - The nutritional status of the loquat trees was investigated using cattle manure
      and commercial fertilizers for three years. The farmyard manure increased N, P,
      K, Mg, Fe and Zn contents of the leaves. No significant difference was found
      between the fertilizer types for trunk growth. Yield efficiency was nearly
      doubled by application of farmyard manure. Fertilizers did not affect the weight
      and shape of the fruits; however, commercial fertilizers led the lower total
      acidity in fruits. It was concluded that the loquat trees grown in sandy soils
      could fulfill their principal nutrient requirements for growth and commercial
      yield with application of farmyard manure.

PMID- 15259610
TI  - Brainstem auditory evoked responses in young urban and rural boys--a comparison.
AB  - Brainstem auditory evoked responses (BAER) were studied in a total of 194 boys in
      the age group between 10-15 yrs taken from a busy metropolitan city and also from
      a relatively quiet town in order to compare their values and to look into the
      probable cause of the difference between them, if any. BAER were tested with the
      help of Compact-4 (Nicolet, USA) instrument using the standard technique. In
      general, the BAER values of the two sample populations were found to be almost
      similar with no gross differences in terms of peak latency and inter peak
      latencies. The values were found to be comparable to adult male values as
      reported earlier.

PMID- 15259611
TI  - Effect of the extract of Thespesia populnea leaves on mice testis.
AB  - Male swiss mice were administered with the leaf extract of Thespesia populnea at
      a daily dose of 400 mg/kg body weight for 15 days and the testis were subjected
      to structural analysis. The structure of the seminiferous tubule in the testis of
      treated animal was elongated. Sertoli cells were enlarged in its structure and
      spermatids became round and disintegrated. It is suggested that the extract of T.
      populnea treatment leads to pathological changes in the seminiferous tubules,
      Sertoli cells and spermatids of the testis.

PMID- 15259612
TI  - Heavy metal pollution in various canals originating from river Yamuna in Haryana.
AB  - Heavy metal pollution due to Fe, Ni, Pb, Cd, Co and Zn in the water of major
      canals originating from the river Yamuna in Haryana was studied. All these metals
      except Zn were found to be present in the Western Yamuna Canal (WYC) exceeding
      the maximum permissible limits. In the Sunder branch (SB), the heavy metal
      concentration was relatively more. Concentrations of the metals were, however,
      relatively less in the highly eutrophicated waters of Agra canal and Gurgaon
      canal as compared to that in WYC but Fe concentration were much higher. Except Zn
      and Ni the metal concentrations exceeded the standard permissible limits in these
      canals also.

PMID- 15259613
TI  - Hydrobiological study of lake Mirik in Darjeeling Himalayas.
AB  - Some hydrobiological features of lake Mirik, situated in the Darjeeling Himalayas
      were studied during May to October, 2000. Water temperature showed abrupt
      fluctuations. The pH was generally acidic. Dissolved oxygen increased steadily
      with increasing rainfall and recorded highest in late August (12.6 mgl(-1)). The
      gross primary productivity had a highest value of 87.50 mg C m(-3) hr(-1).
      Chlorophyceae and Cyanophyceae were identified among phytoplanktons. Zooplanktons
      were represented by Cladocerans and Copepods. The study revealed higher
      concentration of nutrients at certain pockets of the lake, which points to
      increasing human influences in the system, and, the water cannot serve as a
      scarcity alternative for drinking purpose.

PMID- 15259614
TI  - Effect of cybil on reproductive success of wild Drosophila melanogaster.
AB  - Cybil (a synthetic pyrethroid) was used to assess its impact on the reproductive
      success in F1 and F2 generations of wild Drosophila melanogaster. The LC50 has
      been estimated as 0.0267 microl/100 ml food. Reproductive success has been found
      to be affected in addition to fecundity and pupation following toxicity of cybil.

PMID- 15259615
TI  - Antimicrobial resistance among enteric bacteria, isolated from runoff of the
      Gangotri glacier, western Himalaya India.
AB  - An attempt has been made to study antimicrobial resistance among the coliforms,
      faecal coliforms and faecal streptococci isolated from the runoff of the Gangotri
      glacier. The number of multiple antibiotic resistances (MAR) coliform isolates
      increases from upper stretch (33.33%) to lower stretch (83.33%). All faecal
      coliforms (100%) and faecal streptococci (100%) of lower stretch of study area
      showed multiple antibiotic resistances. Among coliforms, the value of Antibiotic
      resistance index (ARI) was found maximum in lower stretch (0.34) followed by
      middle stretch (0.29) and upper stretch (0.25).

PMID- 15259616
TI  - Sensitivity of newly released varieties of rice to herbicides.
AB  - A field experiment was carried out during Kharif 1999 at experimental farm of CSK
      HPKV Palampur to check the sensitivity of newly released varieties to herbicides
      in direct seeded puddled rice. Experiment was conducted in randomized block
      design with nine treatment combinations each replicated thrice. Treatments
      consisted of combinations of three-weed control methods viz., two hand weeding,
      butachlor 2.0 kg/ha and pretilachlor 0.8 kg/ha and three rice varieties RP-2421,
      HPR-957 and HPR-927. It can be concluded from the study that HPR-957 was
      sensitive to butachlor 2.0 kg/ha and pretilachlor 0.8 kg/ha herbicides.

PMID- 15259617
TI  - Assessing acute middle cerebral artery ischemic stroke by quantitative electric
      tomography.
AB  - This paper focuses on the application of quantitative electric tomography (qEEGT)
      to map changes in EEG generators for detection of early signs of ischemia in
      patients with acute middle cerebral artery stroke. Thirty-two patients were
      studied with the diagnosis of acute ischemic stroke of the left middle cerebral
      artery territory, within the first 24 hours of their clinical evolution. Variable
      Resolution Electrical Tomography was used for estimating EEG source generators.
      High resolution source Z-spectra and 3- dimensional images of Z values for all
      the sources at each frequency were obtained for all cases. To estimate
      statistically significant increments and decrements of brain electric activity
      within the frequency spectra, the t-Student vs. Zero test was performed. A
      significant increment of delta activity was observed on the affected vascular
      territory, and a more extensive increment of theta activity was detected. A
      significant alpha decrement was found in the parieto-occipital region of the
      affected cerebral hemisphere (left), and in the medial and posterior region of
      the right hemisphere. These findings suggest that qEEGT Z delta images are
      probably related to the main ischemic core within the affected arterial
      territory; penumbra, diaschisis, edema, might explain those observed theta and
      alpha abnormalities. It was concluded that qEEGT is useful for the detection of
      early signs of ischemia in acute ischemic stroke.

PMID- 15259618
TI  - Visual assessment of selected high amplitude frontopolar slow waves of sleep:
      differences between healthy subjects and apnea patients.
AB  - Slow wave sequences with individually defined amplitude criterion were selected
      manually from frontopolar sleep EEG of eight healthy control subjects and eight
      patients with sleep apnea syndrome. Healthy subjects had clearly more time
      occupied by slow wave sequences in all night sleep. Closer examination revealed
      that the difference in the amount of slow wave sequence time between the groups
      was statistically significant only in the first NREM sleep episode. In other
      words, healthy subjects had more time with slow wave sequences in the first NREM
      sleep episode, where sleep pressure is supposed to be highest. The lower amount
      of slow wave sequences in the apnea patients might reflect the fragmented sleep
      of the patients, inhibiting cortical synchronization.

PMID- 15259619
TI  - Attentional distraction of CNV depending on the spatial focus.
AB  - To investigate the distraction of spatial attention to the task-irrelevant visual
      stimuli, contingent negative variation (CNV) was measured by using a forewarned
      reaction time task in 20 healthy subjects. The lasting emission of light,
      irrelevant to the CNV task, at each perimetric angle of 15 degrees, 30 degrees or
      45 degrees to the fixated point was presented to the subjects. The amplitude of
      early CNV was small only under the light-emission at the angle of 30 degrees. Our
      results indicate that attention is distracted even by the lasting, task
      irrelevant stimuli and that distraction is dependent on the focusing function of
      attention.

PMID- 15259620
TI  - Correlation between P300 and EEG rhythm in schizophrenia.
AB  - We hypothesized that cognitive deficits reflected by P300 abnormality and
      distorted EEG rhythm in schizophrenia, which might share the subcortical
      generation system, could be closely associated with each other. Our goal is to
      assess the relationship between P300 and EEG rhythm generation in schizophrenics.
      Quantitative EEG (QEEG) in resting condition and P300 during auditory oddball
      paradigm were recorded with 25 unmedicated patients. Additionally, lateral
      ventricular-brain ratio (LV-BR), which partially reflects thalamic volume, was
      measured using CT scan. Brief Psychotic Rating Scale (BPRS) and Scale for
      Assessment of Negative Symptoms (SANS) were also rated. P300 amplitudes at Pz
      positively correlated with theta and slow alpha power before pharmacotherapy,
      however, the correlation tended to be confined to fast alpha after
      pharmacotherapy. BPRS and SANS showed no significant correlation with QEEG. High
      frequency bands such as fast alpha and beta showed trends to correlate negatively
      to LV-BR. The lack of correlation between P300 amplitudes and fast alpha power
      before pharmacotherapy, which was restored after pharmacotherapy, might indicate
      thalamocortical dysfunction in schizophrenia.

PMID- 15259621
TI  - The relationship between bilateral spike and wave complexes and focal discharges
      in patients with partial epilepsy.
AB  - The goal of this study was to investigate in patients with partial epilepsy the
      relationship between bilateral spike and wave (BSW) complexes of a generalized
      epilepsy and the focal spikes of partial epilepsy. For the study 300 patients
      were collected, all with focal epilepsy on their last hospital visit: 150 were
      well controlled (C) and 150 were uncontrolled (U), and the number of EEGs was 674
      in the C and 804 in the U groups. BSW were seen at some time in 25% of all
      patients, more often in the U than C patients, especially the irregular 3/sec
      form. The bilateral complexes at times appeared at the onset of the epilepsy,
      usually at the same time with focal discharges, mainly from temporal or frontal
      areas. The U patients showed these complexes at a younger age than the C group
      and continued to be seen often into the 30s, occasionally into the 60s age group.
      The other presentation of the BSW was years after the onset of the focal
      discharges, usually temporal or frontal in location and more often seen in the U
      than C group. The U group showed spikes, many in number as active foci, more
      often than the C group. The discussion deals with the possibility that these
      bilateral spike and wave complexes may represent a reflection of a lowered
      threshold to a seizure.

PMID- 15259622
TI  - Generalized spike-wave discharges with focal onset in a patient with head trauma
      and diffuse cerebral lesions: a case report with EEG and cranial MRI findings.
AB  - The role of cerebral lesions associated with absence seizures, outside the
      frontal lobe, has not been demonstrated by both electroencephalography and
      neuroimaging techniques until now, to our knowledge. We present a case with
      absence seizures and EEGs with generalized 3 Hz spike-wave patterns that were
      preceded by a burst of spike-waves on the right parieto-occipital region. The
      patient had a history of head trauma, and cranial MRI revealed lesions that might
      be responsible for the seizures. The patient's lateralized and localized EEG
      findings were probably a representation of secondary bilateral synchrony (SBS).
      The mechanism of SBS is considerably more complex than a simple triggering of
      generalized spike-wave complexes from a single cortical focus.

PMID- 15259623
TI  - Factors in the interictal record predicting an ictal episode: a case study.
AB  - This report deals with a patient with intractable seizures, who had 64 subdural
      electrodes implanted onto the left frontal and temporal cerebral cortex in
      anticipation of probable seizure surgery. One specific region on the left frontal
      lobe proved to be the focus for both the interictal spikes and also for the ictal
      activity. Our goal was to determine what electrical characteristics in the
      interictal record predicted the ictal episodes. The number of interictal spikes
      and also the amount of fast activity (15-128/sec) progressively increased before
      each of the 5 ictal episodes; an analysis showed that the number of spikes and
      their frequency proved the more significant variable. One other characteristic
      that changed before the ictal episodes was a great decrease in the interval
      between spikes as an example of a diminishing variability or increasing
      periodicity. Thus, the important factors in the interictal record that lead to an
      ictal event are the number of spikes, the amount of fast activity and the
      decreasing variability between the spikes.

PMID- 15259624
TI  - A case of mild Alzheimer's disease accompanied by periodic synchronous
      discharges.
AB  - Periodic synchronous discharges (PSD) on the electroencephalogram can be observed
      in diseases such as Creutzfeldt-Jakob disease, hypoxic encephalopathy and
      Alzheimer's disease (AD). However, in previously reported cases of AD with PSD,
      PSD have only been found many years after the diagnosis of AD. We recently
      encountered a patient with mild AD accompanied by transient PSD. To our
      knowledge, this is the first case report to suggest that PSD can occur in mild
      AD.

PMID- 15259625
TI  - Heroes in community psychiatry: Professor Gerald Caplan.

PMID- 15259626
TI  - Reassessing treatment environments after two decades: client and staff
      perceptions of an Italian community mental health service environment, then and
      now.
AB  - Community-based psychiatric services and programs developed in accordance with
      the 1978 Italian psychiatric reform have now been in operation for a quarter of a
      century. The paper presents the results of a study in which three treatment
      environments of South-Verona, i.e. a general hospital psychiatric ward, a
      community mental health center (CMHC) and two residential facilities have been
      investigated using the Ward Atmosphere Scale (WAS) and the Community Oriented
      Programs Environment Scale (COPES). Staff and patient ratings have been collected
      in the three environments thus allowing comparisons between respondents and
      settings. For the ward and the CMHC, whose staff had already been interviewed
      almost twenty years before, a comparison between studies was also possible.
      Results seem to show that original policies, attitudes and staff commitment have
      successfully survived the passage of time with only minor adjustments and that
      the single-staff module of South-Verona may have effectively contributed in this
      respect.

PMID- 15259627
TI  - The Camberwell Assessment of Need and Behaviour and Symptom Identification Scale
      as routine outcome measures in a psychiatric disability rehabilitation and
      support service.
AB  - While routine outcome measurement is being progressively introduced into mental
      health services, there is little evidence of its potential in disability
      rehabilitation and support services. We report the introduction of a measure of
      need and a self-report measure of mental health problems in such a service in
      which most of the consumers have a principal diagnosis of a schizophrenia
      spectrum disorder. We found that just over half of the consumers with a key
      worker were able and willing to complete these instruments. On average,
      consumers' self-ratings suggested only moderate levels of mental health problems,
      and consumers with schizophrenia identified lower levels of need than their key
      workers. Assessments of need showed more stability over time than assessments of
      mental health problems.

PMID- 15259628
TI  - The impact of day hospital closure on social networks, clinical status, and
      service use: a naturalistic experiment.
AB  - OBJECTIVE: Little research is conducted on service closures. We examined the
      social, clinical and service use impact of the closure of a partial
      hospitalisation service (day hospital) on its users. METHODS: Patients attending
      the closing day hospital were studied at closure and one year after, and compared
      to patients at an unchanged day hospital. RESULTS: The closure did not increase
      use of inpatient beds, primary care or emergency room. Overall clinical
      improvements were similar for both groups as were costs. Social networks of the
      discharged patients decreased. CONCLUSIONS: Closures of services need to be as
      carefully evaluated as new developments.

PMID- 15259629
TI  - Changes in attitudes towards mental illness following exposure.
AB  - Attitudes towards mental patients influence the treatment they receive and
      decisions of policymakers. It is important to modify attitudes of students who
      may work with them. Psychopathology course students (45 visited a mental
      institution, 56 volunteered in it, and 12 neither) and 53 introductory psychology
      students participated in this study. Benevolence, mental hygiene etiology and
      interpersonal etiology (opinions about mental illness scale) improved from
      beginning to end of year. Working proved more important than visiting or
      studying. Visiting increased social restrictiveness. Therefore, a small amount of
      exposure (a visit) can be detrimental. These results point to the possible
      superiority of prolonged, intimate exposure, on an equal basis, in changing
      attitudes towards mental health patients.

PMID- 15259630
TI  - Community-based prevention for suicide in elderly by depression screening and
      follow-up.
AB  - The aim of the study was to evaluate the outcome of a community-based prevention
      program against suicides among the elderly aged 65 and over in the Japanese rural
      town of Joboji (population 7,010), using a quasi-experimental design with two
      neighboring control areas. During the 10-year implementation of the program based
      on strategies including screening for depression, follow up with mental health
      care or psychiatric treatment and health education on depression, the relative
      risks estimated by the age-adjusted odds ratios for both males and females were
      reduced to almost one quarter more than a regional historical trend, with a
      better response to education for females than for males. A community-based
      management for later-life depression with mental health care supported by the
      psychiatric treatment can be effective against suicide among the elderly for both
      males and females.

PMID- 15259631
TI  - Factors influencing social distance toward people with mental illness.
AB  - BACKGROUND: When identifying ways to reduce stigmatization because of mental
      illness it is crucial to understand contributing factors. Social distance-the
      willingness to engage in relationships of varying intimacy with a person--is an
      indicator of public attitudes toward persons with mental illness. METHODS:
      Multiple linear regression analysis of the results of a vignette-based opinion
      survey conducted on a representative population sample in Switzerland (n = 594).
      RESULTS: The level of social distance increases if situations imply 'social
      closeness.' The vignette describing a person with schizophrenia, attitudes to
      general aspects of mental health (lay helping, community psychiatry), emotions
      toward those affected, and the attitude toward consequences of mental illness
      (medical treatment, medication side effects, negative sanctions, e.g. withdrawal
      of the driver license) were found to predict social distance. Demographic factors
      such as age, gender, and the cultural background influence social distance. The
      explained variance (R2) is 44.8%. CONCLUSIONS: Social distance is a multifaceted
      concept influenced by, e.g., socio-economic and cultural factors, but also by the
      respondent's general attitude toward (mental) health issues. These results
      suggest that more knowledge about mental illnesses, especially schizophrenia, may
      increase social distance. The findings presented here may help to focus anti
      stigma campaigns not only on transmission of knowledge, but on integrating
      different approaches.

PMID- 15259632
TI  - The concepts of transient and secular equilibrium are incorrectly described in
      most textbooks, and incorrectly taught to most physics students and residents.
      For the proposition.

PMID- 15259633
TI  - The concepts of transient and secular equilibrium are incorrectly described in
      most textbooks, and incorrectly taught to most physics students and residents.
      Against the proposition:.

PMID- 15259634
TI  - Comparative skin dose measurement in the treatment of anal canal cancer:
      conventional versus conformal therapy.
AB  - The subject of this work was to compare the effect of Conventional and Conformal
      techniques, used for anal canal cancer treatments, on the skin dose deposition.
      Skin dose was measured on a Rando phantom using XR-T GAFCHROMIC film. A skin
      surface dose histogram was constructed and a skin dose profile in the sagittal
      direction of the perineal region was measured, for both techniques. The measured
      skin dose in the anterior and posterior region of the skin exposed to radiation
      is from two to ten times higher when using a conventional technique. In the
      perineal region, an 85% of the prescription isodose line spreads over 25% of the
      perineum for conformal technique as compared to 65% with conventional techniques.
      In addition, conformal technique dose profiles confine better the anatomical
      position of the anal verge than conventional techniques. Results presented in
      this work confirm clinically observed improvement in the radiation-induced
      dermatitis when using the conformal technique.

PMID- 15259635
TI  - Elastographic versus x-ray CT imaging of radio frequency ablation coagulations:
      an in vitro study.
AB  - Techniques to image elasticity parameters (i.e., elastography) have recently
      become of great interest to researchers. In this paper we use conventional
      ultrasound elastography and x-ray CT to image radio frequency (RF) ablation sites
      of excised canine liver enclosed in gelatin. Thermal coagulations of different
      sizes were produced by applying the RF procedure for various times and end point
      temperatures. Dimensions, areas and volumes computed from CT and elastography
      were compared with those on whole mount pathology specimens. Ultrasound
      elastography exhibited high contrast for the thermal coagulations and performed
      better than CT. The correlation between pathology and elastography for this
      sample set of 40 thermal coagulations (r = 0.94 for volume estimation, r = 0.87
      for area estimation) is better than the correlation between pathology and CT (r =
      0.89 for volume estimation, r = 0.82 for area estimation).

PMID- 15259636
TI  - Quantitation of respiratory motion during 4D-PET/CT acquisition.
AB  - We report on the variability of the respiratory motion during 4D-PET/CT
      acquisition. The respiratory motion for five lung cancer patients was monitored
      by tracking external markers placed on the abdomen. CT data were acquired over an
      entire respiratory cycle at each couch position. The x-ray tube status was
      recorded by the tracking system, for retrospective sorting of the CT data as a
      function of respiration phase. Each respiratory cycle was sampled in ten equal
      bins. 4D-PET data were acquired in gated mode, where each breathing cycle was
      divided into ten 500 ms bins. For both CT and PET acquisition, patients received
      audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then
      correlated according to their respiratory phases. The respiratory periods, and
      average amplitude within each phase bin, acquired in both modality sessions were
      then analyzed. The average respiratory motion period during 4D-CT was within 18%
      from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in
      the duration of each 4D-CT bin. This small uncertainty enabled good correlation
      between CT and PET data, on a phase-to-phase basis. Comparison of the average
      amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by
      bin basis show a maximum deviation of approximately 15%. This study has proved
      the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in
      most cases consistent between PET and CT sessions, thereby improving both the
      attenuation correction of PET images, and co-registration of PET and CT images.
      On the other hand, in two patients, there was an increased partial irregularity
      in their breathing motion, which would prevent accurately correlating the
      corresponding PET and CT images.

PMID- 15259637
TI  - A method to improve spatial resolution and smoothness of intensity profiles in
      IMRT treatment planning.
AB  - In IMRT optimization, the size of beamlets used for optimizing the beam intensity
      distributions is a planner-selected parameter. The appropriate setting for the
      beamlet size is critical to the outcome of IMRT planning. With too small beamlets
      the dose calculation can be inaccurate, and the resulting intensity profiles can
      be unnecessarily complex and difficult to generate. Relatively simple intensity
      profiles can be obtained using large beamlets. However, this may compromise the
      conformity of the dose distribution. In this paper we present a method, in which
      multiple beamlet matrices displaced from each other by a shift in MLC leaf travel
      direction are used instead of the single beamlet matrix per beam in a
      conventional method, to achieve finer spatial resolution for the intensity
      distribution than the given beamlet size. Two test cases were used to assess the
      method by the resultant DVHs and dose distributions and characteristic indices of
      the intensity profiles. The results show that this method can produce optimized
      dose distributions that are similar to those produced by the conventional inverse
      planning method with the benefit of smoother intensity profiles that are easier
      to deliver with a computer controlled MLC.

PMID- 15259638
TI  - Physical performance evaluation of a 256-slice CT-scanner for four-dimensional
      imaging.
AB  - We have developed a prototype 256-slice CT-scanner for four-dimensional (4D)
      imaging that employs continuous rotations of a cone-beam. Since a cone-beam scan
      along a circular orbit does not collect a complete set of data to make an exact
      reconstruction of a volume [three-dimensional (3D) image], it might cause
      disadvantages or artifacts. To examine effects of the cone-beam data collection
      on image quality, we have evaluated physical performance of the prototype 256
      slice CT-scanner with 0.5 mm slices and compared it to that of a 16-slice CT
      scanner with 0.75 mm slices. As a result, we found that image noise, uniformity,
      and high contrast detectability were independent of z coordinate. A Feldkamp
      artifact was observed in distortion measurements. Full width at half maximum
      (FWHM) of slice sensitivity profiles (SSP) increased with z coordinate though it
      seemed to be caused by other reasons than incompleteness of data. With regard to
      low contrast detectability, smaller objects were detected more clearly at the
      midplane (z = 0 mm) than at z = 40 mm, though circular-band like artifacts
      affected detection. The comparison between the 16-slice and the 256-slice
      scanners showed better performance for the 16-slice scanner regarding the SSP,
      low contrast detectability, and distortion. The inferiorities of the 256-slice
      scanner in other than distortion measurement (Feldkamp artifact) seemed to be
      partly caused by the prototype nature of the scanner and should be improved in
      the future scanner. The image noise, uniformity, and high contrast detectability
      were almost identical for both CTs. The 256-slice scanner was superior to the 16
      slice scanner regarding the PSF, though it was caused by the smaller transverse
      beam width of the 256-slice scanner. In order to compare both scanners
      comprehensively in terms of exposure dose, noise, slice thickness, and transverse
      spatial resolution, K=Dsigma2ha3 was calculated, where D was exposure dose (CT
      dose index), sigma was magnitude of noise, h was slice thickness (FWHM of SSP),
      and a was transverse spatial resolution (FWHM of PSF). The results showed that
      the K value was 25% larger for the 16-slice scanner, and that the 256-slice
      scanner was 1.25 times more effective than the 16-slice scanner at the midplane.
      The superiority in K value for the 256-slice scanner might be partly caused by
      decrease of wasted exposure with a wide-angle cone-beam scan. In spite of the
      several problems of the 256-slice scanner, it took a volume data approximately
      1.0 mm (transverse) x 1.3 mm (longitudinal) resolution for a wide field of view
      (approximately 100 mm long) along the zeta axis in a 1 s scan if resolution was
      defined by the FWHM of the PSF or the SSP, which should be very useful to take
      dynamic 3D (4D) images of moving organs.

PMID- 15259639
TI  - Feldkamp-type VOI reconstruction from super-short-scan cone-beam data.
AB  - Based on the fan-beam reconstruction formula recently developed by Noo et al.
      [Phys. Med. Biol. 47, 2525-2546 (2002)] we develop a Feldkamp-type algorithm for
      the reconstruction of a volume of interest (VOI) from super-short-scan data. With
      either a circular or spiral scanning locus in our VOI reconstruction scheme, we
      first estimate fan-beam data from cone-beam data using the popular "cosine
      correction" scheme, and perform reconstruction based on Noo's FBP-type fan-beam
      reconstruction. Our proposed algorithm is tested using the three-dimensional (3
      D) Shepp-Logan phantom. The experimental results show that the new algorithm can
      be applied to multi-source 4-D CT with significantly superior temporal resolution
      and temporal consistency relative to the Katsevich algorithm, which is the state
      of the art for exact helical cone-beam reconstruction.

PMID- 15259640
TI  - Development and validation of a CT-3D rotational angiography registration method
      for AVM radiosurgery.
AB  - In this paper a novel technique is proposed and validated for radiosurgery
      treatment planning of arteriovenous malformations (AVMs). The technique was
      developed for frameless radiosurgery by means of the CyberKnife, a nonisocentric,
      linac-based system which allows highly conformed isodose surfaces to be obtained,
      while also being valid for other treatment strategies. The technique is based on
      registration between computed tomography (CT) and three-dimensional rotational
      angiography (3DRA). Tests were initially performed on the effectiveness of the
      correction method for distortion offered by the angiographic system. These
      results determined the registration technique that was ultimately chosen. For CT
      3DRA registration, a twelve-parameter affine transformation was selected, based
      on a mutual information maximization algorithm. The robustness of the algorithm
      was tested by attempting to register data sets increasingly distant from each
      other, both in translation and rotation. Registration accuracy was estimated by
      means of the "full circle consistency test." A registration quality index
      (expressed in millimeters) based on these results was also defined. A hybrid
      subtraction between CT and 3DRA is proposed in order to improve 3D
      reconstruction. Preprocessing improved the ability of the algorithm to find an
      acceptable solution to the registration process. The robustness tests showed that
      data sets must be manually prealigned within approximately 15 mm and 20 degrees
      with respect to all three directions simultaneously. Results of the consistency
      test showed agreement between the quality index and registration accuracy stated
      by visual inspection in 20 good and 10 artificially worsened registration
      processes. The quality index showed values smaller than the maximum voxel size
      (mean 0.8 mm compared to 2 mm) for all successful registrations, while it
      resulted in much greater values (mean 20 mm) for unsuccessful registrations. Once
      registered, the two data sets can be used for CyberKnife treatment planning.
      Target delineation is performed on 3DRA while dose calculation and DRR generation
      are performed on CT. In conclusion, a method was developed for using 3DRA images
      for AVM frameless radiosurgery treatment planning. The method proved to be
      feasible, robust, and accurate for clinical use. 3DRA can be performed at
      different times or locations compared to standard, frame based stereotactic
      angiography. Unlike two-dimensional angiography, 3DRA allows examination of the
      shape of the AVM and of the surrounding target from any arbitrary point of view
      during treatment planning. The method can be applied to any case of intermodality
      registration, is operator-independent, and allows estimation of registration
      quality. Further research is desirable to improve time resolution in order to
      distinguish between feeding and draining vessels.

PMID- 15259641
TI  - Quantitative characterization of edge enhancement in phase contrast x-ray
      imaging.
AB  - The aim of this study was to model the edge enhancement effect in in-line
      holography phase contrast imaging. A simple analytical approach was used to
      quantify refraction and interference contrasts in terms of beam energy and
      imaging geometry. The model was applied to predict the peak intensity and
      frequency of the edge enhancement for images of cylindrical fibers. The
      calculations were compared with measurements, and the relationship between the
      spatial resolution of the detector and the amplitude of the phase contrast signal
      was investigated. Calculations using the analytical model were in good agreement
      with experimental results for nylon, aluminum and copper wires of 50 to 240
      microm diameter, and with numerical simulations based on Fresnel-Kirchhoff
      theory. A relationship between the defocusing distance and the pixel size of the
      image detector was established. This analytical model is a useful tool for
      optimizing imaging parameters in phase contrast in-line holography, including
      defocusing distance, detector resolution and beam energy.

PMID- 15259642
TI  - Design and tests of a portable mini gamma camera.
AB  - Design optimization, manufacturing, and tests, both laboratory and clinical, of a
      portable gamma camera for medical applications are presented. This camera, based
      on a continuous scintillation crystal and a position-sensitive photomultiplier
      tube, has an intrinsic spatial resolution of approximately 2 mm, an energy
      resolution of 13% at 140 keV, and linearities of 0.28 mm (absolute) and 0.15 mm
      (differential), with a useful field of view of 4.6 cm diameter. Our camera can
      image small organs with high efficiency and so it can address the demand for
      devices of specific clinical applications like thyroid and sentinel node
      scintigraphy as well as scintimammography and radio-guided surgery. The main
      advantages of the gamma camera with respect to those previously reported in the
      literature are high portability, low cost, and weight (2 kg), with no significant
      loss of sensitivity and spatial resolution. All the electronic components are
      packed inside the minigamma camera, and no external electronic devices are
      required. The camera is only connected through the universal serial bus port to a
      portable personal computer (PC), where a specific software allows to control both
      the camera parameters and the measuring process, by displaying on the PC the
      acquired image on "real time." In this article, we present the camera and
      describe the procedures that have led us to choose its configuration. Laboratory
      and clinical tests are presented together with diagnostic capabilities of the
      gamma camera.

PMID- 15259643
TI  - Classification of breast tissue density by optical transillumination
      spectroscopy: optical and physiological effects governing predictive value.
AB  - Preventive oncology is in need of a risk assessment technique that can identify
      individuals at high risk for breast cancer and has the ability to monitor the
      efficacy of a risk reducing intervention. Optical transillumination spectroscopy
      (OTS) gives information about breast tissue composition and tissue density. OTS
      is noninvasive and in contrast to mammography, uses nonionizing radiation. It is
      safe and can be used frequently on younger women, potentially permitting early
      risk detection and thus increasing the time available for risk reduction
      interventions to assert their influence. Before OTS can be used as a risk
      assessment and/or monitoring technique, its predictive ability needs to be
      demonstrated and maximized through the construction of various mathematical
      models relating OTS and breast tissue density, and hence, risk. To establish a
      correlation between OTS and mammographic density principal components analysis
      (PCA), using risk classification, is calculated. The PCA scores are presented in
      three-dimensional cluster plots and a plane of differentiation that separates the
      high and low tissue densities is used to calculate the predictive value.
      Stratification of PCA for measurement position on the breast in cranial-caudal
      projection is introduced. Analysis of PCA scores as a function of the volunteer's
      age and body mass index (BMI) is examined. A small but significant correlation
      between the component scores and age or BMI is noted but the correlation is
      dependent on the tissue density category examined. Correction of the component
      scores for age and BMI is not recommended, since a priori knowledge of a woman's
      breast tissue density is required. Stratification for the center and distal
      measurement positions provide a predictive value for OTS above 96%.

PMID- 15259644
TI  - A model to predict bladder shapes from changes in bladder and rectal filling.
AB  - The purpose of this study is to develop a model that quantifies in three
      dimensions changes in bladder shape due to changes in bladder and/or rectal
      volume. The new technique enables us to predict changes in bladder shape over a
      short period of time, based on known urinary inflow. Shortly prior to the
      treatment, the patient will be scanned using a cone beam CT scanner (x-ray volume
      imager) that is integrated with the linear accelerator. After (automated)
      delineation of the bladder, the model will be used to predict the short-term
      shape changes of the bladder for the time interval between image acquisition and
      dose delivery. The model was developed using multiple daily CT scans of the
      pelvic area of 19 patients. For each patient, the rigid bony structure in follow
      up scans was matched to that of the planning CT scan, and the outer bladder and
      rectal wall were delineated. Each bladder wall was subdivided in 2500 domains. A
      fixed reference point inside the bladder was used to calculate for each bladder
      structure a "Mercator-like" 2D scalar map (similar to a height map of the globe),
      containing the distances from this reference point to each domain on the bladder
      wall. Subsequently, for all bladder shapes of a patient and for all domains on
      the wall individually, the distance to the reference point was fitted by a linear
      function of both bladder and rectal volume. The model uses an existing bladder
      structure to create a new structure via expansion (or contraction), until the
      expressed volume is reached. To evaluate the predictive power of the model, the
      jack-knife method was used. The errors in the fitting procedure depended on the
      part of the bladder and range from 0 to 0.5 cm (0.2 cm on average). It was found
      that a volume increase of 150 cc can lead to a displacement up to about 2.5 cm of
      the cranial part of the bladder. With the model, the uncertainty in the position
      of the bladder wall can be reduced down to a maximum value of about 0.5 cm in
      case the bladder volume increase is known. Furthermore, it was found that a
      change in rectal filling causes a shift of the bladder, while its shape is hardly
      influenced. In conclusion, we developed a model that describes the bladder shape
      and position as a function of the bladder volume and the rectal filling. The
      model accurately describes the complex shape of the bladder as it works on each
      domain of the bladder separately.

PMID- 15259645
TI  - A multimodality vascular imaging phantom with fiducial markers visible in DSA,
      CTA, MRA, and ultrasound.
AB  - The objective was to design a vascular phantom compatible with digital
      subtraction angiography, computerized tomography angiography, ultrasound and
      magnetic resonance angiography (MRA). Fiducial markers were implanted at precise
      known locations in the phantom to facilitate identification and orientation of
      plane views from three-dimensional (3-D) reconstructed images. A vascular conduit
      connected to tubing at the extremities of the phantom ran through an agar-based
      gel filling it. A vessel wall in latex was included around the conduit to avoid
      diffusion of contrast agents. Using a lost-material casting technique based on a
      low melting point metal, geometries of pathological vessels were modeled. During
      the experimental testing, fiducial markers were detectable in all modalities
      without distortion. No leak of gadolinium through the vascular wall was observed
      on MRA after 5 hours. Moreover, no significant deformation of the vascular
      conduit was noted during the fabrication process (confirmed by microtome slicing
      along the vessel). The potential use of the phantom for calibration, rescaling,
      and fusion of 3-D images obtained from the different modalities as well as its
      use for the evaluation of intra- and inter-modality comparative studies of
      imaging systems are discussed. In conclusion, the vascular phantom can allow
      accurate calibration of radiological imaging devices based on x-ray, magnetic
      resonance and ultrasound and quantitative comparisons of the geometric accuracy
      of the vessel lumen obtained with each of these methods on a given well defined 3
      D geometry.

PMID- 15259646
TI  - Geometrical accuracy and fusion of multimodal vascular images: a phantom study.
AB  - The aim of this work was to compare the geometrical accuracy of x-ray
      angiography, magnetic resonance imaging (MRI), x-ray computed tomography (XCT),
      and ultrasound imaging (B-mode and IVUS, or intravascular ultrasound) for
      measuring the lumen diameters of blood vessels. An image fusion method was also
      developed to improve these measurements. The images were acquired from a phantom
      that mimic vessels of known diameters. After acquisition, the multimodal images
      were coregistered by manual alignment of fiducial markers, and then by
      maximization of mutual information. The fusion method was performed by means of a
      fuzzy logic modeling approach followed by a combination process based on a
      possibilistic theory. The results showed (i) the better geometrical accuracy of
      XCT and IVUS compared to the other modalities, and (ii) the better accuracy and
      smaller variability of fused images compared to single modalities, with respect
      to most diameters investigated. For XCT, the error varied from 0.4% to 5.4%,
      depending on the vessel diameter that ranged from 0.93 to 6.24 mm. For IVUS, the
      error ranged from -0.3% to 1.7% but the smallest vessel (0.93 mm) could not be
      investigated because of the probe size. Compared to others fusion schemes, the
      XCT-MRI fused images provided the best results for both accuracy (from -1.6% to
      0.2% for the three largest vessels) and robustness (mean relative error of 1.9%).
      To conclude, this work underlined both the usefulness of the multimodality
      vascular phantom as a validation tool and the utility of image fusion in the
      vascular context.

PMID- 15259647
TI  - Description and characterization of the novel hyperthermia- and thermoablation
      system MFH 300F for clinical magnetic fluid hyperthermia.
AB  - Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep
      tissues by overcoming limitations of conventional heat treatments. After
      infiltration of the target tissue with nanosized magnetic particles, the power of
      an alternating magnetic field is transformed into heat. The combination of the
      100 kHz magnetic field applicator MFH 300F and the magnetofluid (MF), which both
      are designed for medical use, is investigated with respect to its dosage
      recommendations and clinical applicability. We found a magnetic field strength of
      up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture
      height up to 300 mm. The specific absorption rate (SAR) can be controlled
      directly by the magnetic field strength during the treatment. The relationship
      between magnetic field strength and the iron normalized SAR (SAR(Fe)) is only
      slightly depending on the concentration of the MF and can be used for planning
      the target SAR. The achievable energy absorption rates of the MF distributed in
      the tissue is sufficient for either hyperthermia or thermoablation. The fluid has
      a visible contrast in therapeutic concentrations on a CT scanner and can be
      detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and
      practicability for heat treatment in deep regions of the human body.

PMID- 15259648
TI  - Feasibility of optimizing the dose distribution in lung tumors using fluorine-18
      fluorodeoxyglucose positron emission tomography and single photon emission
      computed tomography guided dose prescriptions.
AB  - The information provided by functional images may be used to guide radiotherapy
      planning by identifying regions that require higher radiation dose. In this work
      we investigate the dosimetric feasibility of delivering dose to lung tumors in
      proportion to the fluorine-18-fluorodeoxyglucose activity distribution from
      positron emission tomography (FDG-PET). The rationale for delivering dose in
      proportion to the tumor FDG-PET activity distribution is based on studies showing
      that FDG uptake is correlated to tumor cell proliferation rate, which is shown to
      imply that this dose delivery strategy is theoretically capable of providing the
      same duration of local control at all voxels in tumor. Target dose delivery was
      constrained by single photon emission computed tomography (SPECT) maps of normal
      lung perfusion, which restricted irradiation of highly perfused lung and imposed
      dose-function constraints. Dose-volume constraints were imposed on all other
      critical structures. All dose-volume/function constraints were considered to be
      soft, i.e., critical structure doses corresponding to volume/function constraint
      levels were minimized while satisfying the target prescription, thus permitting
      critical structure doses to minimally exceed dose constraint levels. An intensity
      modulation optimization methodology was developed to deliver this radiation, and
      applied to two lung cancer patients. Dosimetric feasibility was assessed by
      comparing spatially normalized dose-volume histograms from the nonuniform dose
      prescription (FDG-PET proportional) to those from a uniform dose prescription
      with equivalent tumor integral dose. In both patients, the optimization was
      capable of delivering the nonuniform target prescription with the same ease as
      the uniform target prescription, despite SPECT restrictions that effectively
      diverted dose from high to low perfused normal lung. In one patient, both
      prescriptions incurred similar critical structure dosages, below dose
      volume/function limits. However, in the other patient, critical structure dosage
      from the nonuniform dose prescription exceeded dose-volume/function limits, and
      greatly exceeded that from the uniform dose prescription. Strict compliance to
      dose-volume/ function limits would entail reducing dose proportionality to the
      FDG-PET activity distribution, thereby theoretically reducing the duration of
      local control. Thus, even though it appears feasible to tailor lung tumor dose to
      the FDG-PET activity distribution, despite SPECT restrictions, strict adherence
      to dose-volume/function limits could compromise the effectiveness of functional
      image guided radiotherapy.

PMID- 15259650
TI  - Geometric studies on variable radius spiral cone-beam scanning.
AB  - The goal is to perform geometric studies on cone-beam CT scanning along a three
      dimensional (3D) spiral of variable radius. First, the background for variable
      radius spiral cone-beam scanning is given in the context of electron-beam
      CT/micro-CT. Then, necessary and sufficient conditions are proved for existence
      and uniqueness of PI lines inside the variable radius 3D spiral. These results
      are necessary steps toward exact cone-beam reconstruction from a 3D spiral scan
      of variable radius, adapting Katsevich's formula for the standard helical cone
      beam scanning. It is shown in the paper that when the longitudinally projected
      planar spiral is not always convex toward the origin, the PI line may not be
      unique in the envelope defined by the tangents of the spiral. This situation can
      be avoided by using planar spirals whose curvatures are always positive. Using
      such a spiral, a longitudinally homogeneous region inside the corresponding 3D
      spiral is constructed in which any point is passed by one and only one PI line,
      provided the angle omega between planar spiral's tangent and radius is bounded by
      [omega - 90 degrees] < or = < epsilon for some positive epsilon < or = 32.48
      degrees. If the radius varies monotonically, this region is larger and one may
      allow epsilon < or = 51.85 degrees. Examples for 3D spirals based on logarithmic
      and Archimedean spirals are given. The corresponding generalized Tam-Danielsson
      detection windows are also formulated.

PMID- 15259649
TI  - Solid-state fluoroscopic imager for high-resolution angiography: physical
      characteristics of an 8 cm x 8 cm experimental prototype.
AB  - In this paper, the performance of an 8 cm x 8 cm three-side buttable charge
      coupled device (CCD)-based imager specially designed for high-resolution
      fluoroscopy and operating in fluoroscopic (30 frames/second) mode is presented in
      terms of the presampling modulation transfer function (MTF), noise power spectrum
      (NPS), and detective quantum efficiency (DQE). The 8 cm x 8 cm CCD imager is
      coupled to a 450 microm thick CsI:Tl scintillator by nondemagnifying (straight,
      1:1) fiberoptics. The CCD imager has a fundamental pixel pitch of 39 microm and
      incorporates an optically opaque interline (data) channel. The CCD imager was
      operated at 156 microm pixel pitch by binning 4 x 4 adjacent pixels prior to
      readout. The fluoroscopic image lag was measured and accounted for in the DQE
      estimate to provide lag-corrected DQE. The measured limiting spatial resolution
      at 10% presampling MTF with the imager operated at 156 microm pixel pitch
      (Nyquist sampling limit: 3.21 cy/mm) was 3.6 cy/mm. In the pulsed fluoroscopic
      mode, the first-frame image lag was less than 0.9%. The lag-corrected DQE(0) of
      approximately 0.62 was achieved even at a low fluoroscopic exposure rate of 1
      microR/frame. Grid phantom measurements indicate no appreciable distortion.
      Results from DQE and image lag measurements at fluoroscopic exposure rates
      combined with the high spatial resolution observed from the MTF suggest that this
      type of imager or its variants may be a potential candidate for high-resolution
      neuro-interventional imaging, cardiovascular imaging, pediatric angiography, and
      small animal imaging. Since the CCD is three-side buttable, four such CCD modules
      can be joined to form a 2 x 2 matrix providing a field of view of 16 cm x 16 cm.

PMID- 15259651
TI  - The design and the dosimetry of bi-nuclide radioactive ophthalmic applicators.
AB  - A novel type of applicator for the treatment of intra-ocular tumors has been
      developed, based on the two radionuclides 106Ru/106Rh and 125I. The dose
      distribution of this ophthalmic plaque combines advantageous features of both
      radionuclides and can be optimally adapted to a tumor thickness in the range 6.5
      9 mm, a size which is beyond the dosimetric limitations of the 106Ru/106Rh plaque
      therapy. Compared with 125I plaques a bi-nuclide plaque allows to maintain the
      tumor dosage while the dose in the irradiated volume outside of the target volume
      is significantly reduced. Consequently, radiosensitive structures within the eye
      can be spared more effectively. Dedicated methods have been developed for the
      dosimetry of this plaque. These methods are based on our own extensive dosimetric
      investigations with plastic scintillators. The precondition was the availability,
      developed in recent years, of a more accurate determination of the absolute dose
      rate to water of beta- and low energy emitters.

PMID- 15259652
TI  - A procedure to determine the radiation isocenter size in a linear accelerator.
AB  - Measurement of radiation isocenter is a fundamental part of commissioning and
      quality assurance (QA) for a linear accelerator (linac). In this work we present
      an automated procedure for the analysis of the stars-shots employed in the
      radiation isocenter determination. Once the star-shot film has been developed and
      digitized, the resulting image is analyzed by scanning concentric circles
      centered around the intersection of the lasers that had been previously marked on
      the film. The center and the radius of the minimum circle intersecting the
      central rays are determined with an accuracy and precision better than 1% of the
      pixel size. The procedure is applied to the position and size determination of
      the radiation isocenter by means of the analysis of star-shots, placed in
      different planes with respect to the gantry, couch and collimator rotation axes.

PMID- 15259653
TI  - Electron beam therapy with coil-generated magnetic fields.
AB  - This paper presents an initial study on the issues involved in the practical
      implementation of the use of transverse magnetic fields in electron beam therapy.
      By using such magnetic fields the dose delivered to the tumor region can increase
      significantly relative to that deposited to the healthy tissue. Initially we
      calculated the magnetic fields produced by the Helmholtz coil and modified
      Helmholtz coil configurations. These configurations, which can readily be used to
      generate high intensity magnetic fields, approximate the idealized magnetic
      fields studied in our previous publications. It was therefore of interest to
      perform a detailed study of the fields produced by these configurations. Electron
      beam dose distributions for 15 MeV electrons were calculated using the ACCEPTM
      code for a 3T transverse magnetic field produced by the modified Helmholtz
      configuration. The dose distribution was compared to those obtained with no
      magnetic field. The results were similar to those obtained in our previous work,
      where an idealized step function magnetic field was used and a 3T field was shown
      to be the optimal field strength. A simpler configuration was also studied in
      which a single external coil was used to generate the field. Electron dose
      distributions are also presented for a given geometry and given magnetic field
      strength using this configuration. The results indicate that this method is more
      difficult to apply to radiotherapy due to its lack of symmetry and its
      irregularity. For the various configurations dealt with here, a major problem is
      the need to shield the magnetic field in the beam propagation volume, a topic
      that must be studied in detail.

PMID- 15259654
TI  - A graph-searching method for MLC leaf sequencing under constraints.
AB  - A new leaf-sequencing algorithm for step-and-shoot IMRT that is based on a graph
      searching technique is described. An iterative process guided by a quantitative
      measure for the complexity of the initial or residual intensity pattern is used
      to identify the field segments shaped by a multileaf collimator (MLC). Given a
      user selected number of intensity levels, the algorithm searches deliverable
      segment candidates considering all intensity levels and two collimator positions
      separated by 90 degrees. The candidates for each intensity level are obtained as
      the least number of segments to cover the areas with equal or higher intensity.
      The shape of a deliverable segment is adjusted by leaving out certain beam
      elements for later delivery if this results in a simpler residual intensity
      pattern and the segment is still deliverable. For a MLC design that does not
      allow leaf interdigitation, it is initially assumed that a single segment cannot
      cover two disjoined areas. Among all candidates the segment with the greatest
      reduction of the complexity of the residual intensity distribution is chosen for
      the current step of iteration. The iterative process generates a set of
      deliverable segments of simply connected areas. These segments are combined later
      under specific MLC constraints. Different orders of segment combination are
      considered for minimizing the beam-on time. The final segments are sequenced to
      minimize the leaf travel. This algorithm has been tested using randomly generated
      intensity distributions and clinical cases for the Varian, Siemens, and Elekta
      MLC systems. The results show that as the number of intensity levels is
      increased, the numbers of segments and MUs increase only modestly. Using two
      collimator angles results in decreases in the required number of segments and the
      number of monitor units that can be as much as 20%.

PMID- 15259655
TI  - Incorporation of an iterative, linear segmentation routine into a mammographic
      mass CAD system.
AB  - In previous research, we have developed a computer-aided detection (CAD) system
      designed to detect masses in mammograms. The previous version of our system
      employed a simple but imprecise method to localize the masses. In this research,
      we present a more robust segmentation routine for use with mammographic masses.
      Our hypothesis is that by more accurately describing the morphology of the
      masses, we can improve the CAD system's ability to distinguish masses from other
      mammographic structures. To test this hypothesis, we incorporated the new
      segmentation routine into our CAD system and examined the change in performance.
      The developed iterative, linear segmentation routine is a gray level-based
      procedure. Using the identified regions from the previous CAD system as the
      initial seeds, the new segmentation algorithm refines the suspicious mass borders
      by making estimates of the interior and exterior pixels. These estimates are then
      passed to a linear discriminant, which determines the optimal threshold between
      the interior and exterior pixels. After applying the threshold and identifying
      the object's outline, two constraints on the border are applied to reduce the
      influence of background noise. After the border is constrained, the process
      repeats until a stopping criterion is reached. The segmentation routine was
      tested on a study database of 183 mammographic images extracted from the Digital
      Database for Screening Mammography. Eighty-three of the images contained 50
      malignant and 50 benign masses; 100 images contained no masses. The previously
      developed CAD system was used to locate a set of suspicious regions of interest
      (ROIs) within the images. To assess the performance of the segmentation
      algorithm, a set of 20 features was measured from the suspicious regions before
      and after the application of the developed segmentation routine. Receiver
      operating characteristic (ROC) analysis was employed on the ROIs to examine the
      discriminatory capabilities of each individual feature before and after the
      segmentation routine. A statistically significant performance increase was found
      in many of the individual features, particularly those describing the mass
      borders. To examine how the incorporation of the segmentation routine affected
      the performance of the overall CAD system, free-response ROC (FROC) analysis was
      employed. When considering only malignant masses, the FROC performance of the
      system with the segmentation routine appeared better than the previous system.
      When detecting 90% of the malignant masses, the previous system achieved 4.9
      false positives per image (FPpI) compared to the post-segmentation system's 4.2
      FPpI. At 80% sensitivity, the respective FPpI were 3.5 and 1.6.

PMID- 15259656
TI  - Treatment planning dosimetric parameters for 192Ir seed at short distances:
      effects of air channels and neighboring seeds based on Monte Carlo study.
AB  - The dose distributions around two different arrangements of a single radioactive
      192Ir seed in water, (1) with air channels at the ends, and (2) surrounded by two
      nonactive ("dummy") seeds on both longitudinal ends, were calculated using MCNP4C
      Monte Carlo simulations at distances up to 1 cm. The contributions from beta
      particles and electrons emitted by 192Ir were included in the calculations. The
      effects of (a) the air channels at the seed ends and (b) the interference effect
      of the dummy seeds on the dose distribution were quantified and compared. It was
      found that the dummy seeds do not cause significant dose reduction for radial
      distances beyond 0.05 cm from the seed center. It is decided to report the dose
      rate values and the dosimetric parameters in TG43 format for a single seed with
      air channels for use in treatment planning computer systems. The dose rate
      constant (at 1 cm) of 192Ir seed, lambda, is 1.108 cGyU(-1) h(-1). The values of
      radial dose function, g(r), are within 1% from the TG43 recommended polynomial
      fit, except for distances within 0.08 cm. The anisotropy function, F(r, theta),
      attains large values near the seed ends and shallow angles (up to 8), as well as
      many values greater than 2 at the 20 degrees polar angle. Treatment planning
      systems involving intravascular brachytherapy do not compromise the accuracy for
      dosimetry of multiple seed trains by summing single seed values in water.

PMID- 15259657
TI  - Evaluation of the new cesium-131 seed for use in low-energy x-ray brachytherapy.
AB  - Characterization measurements and calculations were performed on a new medical
      seed developed by IsoRay Inc. in Richland, Washington, that utilizes the short
      lived isotope 131Cs. This model has recently received FDA 510(k) clearance. The
      objective of this work was to characterize the dosimetric properties of the new
      seed according to the AAPM Task Group 43 recommendations. Cesium-131 is a low
      energy x-ray emitter, with the most prominent peaks in the 29 keV to 34 keV
      region. The intended application is brachytherapy for treating cancers in
      prostate, breast, head and neck, lung, and pancreas. The evaluations performed
      included air-kerma strength, radial dose function, anisotropy in phantom, half
      life, energy spectra, and internal activity. The results indicate the CS-1 seeds
      have a dose-rate constant of 0.915 cGy hr(-1) U(-1) in water, dose penetration
      characteristics similar to 125I and 103Pd, anisotropy function values on the
      order of 0.71 at short distances and small angles, and an average anisotropy
      factor of 0.964. The overall dosimetric characteristics are similar to 125I and
      103Pd seeds with the exception of half-life, which is 9.7 days, as compared to 17
      days for 103Pd and 60 days for 125I. The shorter half-life may offer significant
      advantages in biological effectiveness.

PMID- 15259658
TI  - Automatic generation of anatomy-based MLC fields in aperture-based IMRT.
AB  - We have developed an algorithm to automatically generate anatomy-based MLC
      fields. For each beam, a first field is adjusted to the projection of the target
      in a beam's eye view, allowing subsequent fields to be derived from this
      conformal field by removing the overlapping surface of each organ at risk,
      respectively. The projections are based on a surface sampling of the anatomical
      structures. On top of the MLC mechanical constraints, verification constraints
      are imposed on the MLC segments, in order to get reliable dosimetry using a
      commercial dose calculation engine. Thus, in each direction, the aperture's cross
      section must be greater than a specified threshold, in our case 2 cm.
      Furthermore, junctions are not tolerated in order to avoid underdosage, for
      instance from the tongue-and-groove effect. The use of such MLC fields simplifies
      the verification process. The performance of the algorithm is illustrated for
      head and neck, thorax and prostate cases. Only a fraction of a second of CPU time
      is required to perform the segmentation for each beam.

PMID- 15259659
TI  - Simultaneous optimization of beam orientations, wedge filters and field weights
      for inverse planning with anatomy-based MLC fields.
AB  - As an alternative between manual planning and beamlet-based IMRT, we have
      developed an optimization system for inverse planning with anatomy-based MLC
      fields. In this system, named Ballista, the orientation (table and gantry), the
      wedge filter and the field weights are simultaneously optimized for every beam.
      An interesting feature is that the system is coupled to Pinnacle3 by means of the
      PinnComm interface, and uses its convolution dose calculation engine. A fully
      automatic MLC segmentation algorithm is also included. The plan evaluation is
      based on a quasi-random sampling and on a quadratic objective function with
      penalty-like constraints. For efficiency, optimal wedge angles and wedge
      orientations are determined using the concept of the super-omni wedge. A bound
      constrained quasi-Newton algorithm performs field weight optimization, while a
      fast simulated annealing algorithm selects the optimal beam orientations.
      Moreover, in order to generate directly deliverable plans, the following
      practical considerations have been incorporated in the system: collision between
      the gantry and the table as well as avoidance of the radio-opaque elements of a
      table top. We illustrate the performance of the new system on two patients. In a
      rhabdomyosarcoma case, the system generated plans improving both the target
      coverage and the sparing of the parotide, as compared to a manually designed
      plan. In the second case presented, the system successfully produced an adequate
      plan for the treatment of the prostate while avoiding both hip prostheses. For
      the many cases where full IMRT may not be necessary, the system efficiently
      generates satisfactory plans meeting the clinical objectives, while keeping the
      treatment verification much simpler.

PMID- 15259660
TI  - An observer study comparing spot imaging regions selected by radiologists and a
      computer for an automated stereo spot mammography technique.
AB  - We are developing an automated stereo spot mammography technique for improved
      imaging of suspicious dense regions within digital mammograms. The technique
      entails the acquisition of a full-field digital mammogram, automated detection of
      a suspicious dense region within that mammogram by a computer aided detection
      (CAD) program, and acquisition of a stereo pair of images with automated
      collimation to the suspicious region. The latter stereo spot image is obtained
      within seconds of the original full-field mammogram, without releasing the
      compression paddle. The spot image is viewed on a stereo video display. A
      critical element of this technique is the automated detection of suspicious
      regions for spot imaging. We performed an observer study to compare the
      suspicious regions selected by radiologists with those selected by a CAD program
      developed at the University of Michigan. True regions of interest (TROIs) were
      separately determined by one of the radiologists who reviewed the original
      mammograms, biopsy images, and histology results. We compared the radiologist and
      computer-selected regions of interest (ROIs) to the TROIs. Both the radiologists
      and the computer were allowed to select up to 3 regions in each of 200 images
      (mixture of 100 CC and 100 MLO views). We computed overlap indices (the overlap
      index is defined as the ratio of the area of intersection to the area of
      interest) to quantify the agreement between the selected regions in each image.
      The averages of the largest overlap indices per image for the 5 radiologist-to
      computer comparisons were directly related to the average number of regions per
      image traced by the radiologists (about 50% for 1 region/image, 84% for 2
      regions/image and 96% for 3 regions/image). The average of the overlap indices
      with all of the TROIs was 73% for CAD and 76.8% +/- 10.0% for the radiologists.
      This study indicates that the CAD determined ROIs could potentially be useful for
      a screening technique that includes stereo spot mammography imaging.

PMID- 15259661
TI  - MRI/TRUS data fusion for prostate brachytherapy. Preliminary results.
AB  - Prostate brachytherapy involves implanting radioactive seeds (I125 for instance)
      permanently in the gland for the treatment of localized prostate cancers, e.g.,
      cT1c-T2a N0 M0 with good prognostic factors. Treatment planning and seed
      implanting are most often based on the intensive use of transrectal ultrasound
      (TRUS) imaging. This is not easy because prostate visualization is difficult in
      this imaging modality particularly as regards the apex of the gland and from an
      intra- and interobserver variability standpoint. Radioactive seeds are implanted
      inside open interventional MR machines in some centers. Since MRI was shown to be
      sensitive and specific for prostate imaging whilst open MR is prohibitive for
      most centers and makes surgical procedures very complex, this work suggests
      bringing the MR virtually in the operating room with MRI/TRUS data fusion. This
      involves providing the physician with bi-modality images (TRUS plus MRI) intended
      to improve treatment planning from the data registration stage. The paper
      describes the method developed and implemented in the PROCUR system. Results are
      reported for a phantom and first series of patients. Phantom experiments helped
      characterize the accuracy of the process. Patient experiments have shown that
      using MRI data linked with TRUS data improves TRUS image segmentation especially
      regarding the apex and base of the prostate. This may significantly modify
      prostate volume definition and have an impact on treatment planning.

PMID- 15259662
TI  - Treatment plan optimization incorporating respiratory motion.
AB  - Similar to conventional conformal radiotherapy, during lung tomotherapy, a motion
      margin has to be set for respiratory motion. Consequently, large volume of normal
      tissue is irradiated by intensive radiation. To solve this problem, we have
      developed a new motion mitigation method by incorporating target motion into
      treatment optimization. In this method, the delivery-breathing correlation is
      determined prior to treatment plan optimization. Beamlets are calculated by using
      the CT images at the corresponding breathing phases from a dynamic (four
      dimensional) image sequence. With the displacement vector fields at different
      breathing phases, a set of deformed beamlets is obtained by mapping the dose to
      the primary phase. Optimization incorporating motion is then performed by using
      the deformed beamlets obtained by dose mapping. During treatment delivery, the
      same breathing-delivery correlation can be reproduced by instructing the patient
      to breathe following a visually displayed guiding cycle. This method was tested
      using a computer-simulated deformable phantom and a real lung case. Results show
      that treatment optimization incorporating motion achieved similar high dose
      conformality on a mobile target compared with static delivery. The residual
      motion effects due to imperfect breathing tracking were also analyzed.

PMID- 15259663
TI  - Practicability of protontherapy using compact laser systems.
AB  - Protontherapy is a well-established approach to treat cancer due to the favorable
      ballistic properties of proton beams. Nevertheless, this treatment is today only
      possible with large scale accelerator facilities which are very difficult to
      install at existing hospitals. In this article we report on a new approach for
      proton acceleration up to energies within the therapeutic window between 60 and
      200 MeV by using modern, high intensity and compact laser systems. By focusing
      such laser beams onto thin foils we obtained on target intensities of 6 x 10(19)
      W/cm2, which is sufficient to produce a well-collimated proton beam with an
      energy of up to 10 MeV. These results are in agreement with numerical simulations
      and indicate that proton energies within the therapeutic window should be
      obtained in the very near future using such economical and very compact laser
      systems. Hence, this approach could revolutionize cancer treatment by bringing
      the "lab to the hospital-rather than the hospital to the lab".

PMID- 15259664
TI  - An extensive log-file analysis of step-and-shoot intensity modulated radiation
      therapy segment delivery errors.
AB  - We present a study to evaluate the monitor unit (MU), dosimetric, and leaf-motion
      errors found in the delivery of 91 step-and-shoot IMRT treatment plans performed
      at three nominal dose rates using a dual modality high energy Linac (Varian 2100
      C/D, Varian Medical Systems Inc., Palo Alto, CA) equipped with a 120-leaf
      multileaf collimator (MLC). The analysis was performed by studying log files
      generated by the MLC controller system. Recent studies by our group have
      validated that the automatically generated MLC log files accurately record the
      actual system delivery. A total of 635 beams were delivered at three nominal dose
      rates: 100, 300, and 600 MU/min. The log files were manually retrieved and
      analysis software was developed to extract the recorded MU delivery and leaf
      positions for each segment. Our analysis revealed that the magnitude of segment
      MU errors were independent of the planned segment MUs. Segment MU errors were
      found to increase with dose rate having maximum errors per segment of +/-1.8 MU
      at 600 MU/min, +/-0.8 MU at 300 MU/min, and +/-0.5 MU at 100 MU/min. The total
      absolute MU error in each plan was observed to increase with the number of plan
      segments, with the trend increasing more rapidly for higher dose rates. Three
      dimensional dose distributions were recomputed based on the observed segment MU
      errors for three plans with large cumulative absolute MU errors. Comparison with
      the original treatment plans indicated no clinically significant consequences due
      to these errors. In addition, approximately 80% of the total segment deliveries
      reported at least one collimator leaf moving at least 1 mm (projected at
      isocenter) during segment delivery. Such errors occur near the end of segment
      delivery and have been previously observed by our group using a fast video-based
      electronic portal imaging device. At 600 MU/min, between 5% and 23% of the plan
      MUs were delivered during leaf motion that had exceeded a 1 mm position
      tolerance. These leaf motion errors were not included in the treatment plan
      recalculations performed in this study.

PMID- 15259665
TI  - Impact of resolution and noise characteristics of digital radiographic detectors
      on the detectability of lung nodules.
AB  - One of the unanswered questions in digital radiography is the connection between
      physical image quality metrics and clinical detection performance. In this paper,
      we examine the impact of two physical metrics, resolution and noise, on the
      detectability of nodules in a pulmonary background for specific digital
      radiographic detectors. A detection experiment was performed on a simulated image
      set using anatomical backgrounds from a high-quality lung radiograph and three
      different simulated nodule sizes (2-3.5 mm). The resolution and noise of the
      resulting images were modified using existing routines to simulate a selenium
      based and a cesium iodide-based flat-panel detector at comparable exposures. A
      location-known-exactly (LKE) observer performance experiment was performed in
      which four experienced chest radiologists and three physicists specializing in
      chest radiology scored the images. The data from the observer experiment were
      analyzed by receiver operating characteristic (ROC) methodology. The
      detectability, as measured by the parameter Az, was higher for the selenium
      detector than the cesium iodide detector for all nodule sizes by an average of
      8.5%. For one nodule size (2.75 mm), the difference between detectors was
      statistically significant (p < 0.01). The findings indicate that for the
      particular task studied, the superior resolution performance of the selenium
      based detector provided better detectability of subtle lung nodules even though
      the images had greater noise than images obtained with the cesium iodide
      detector.

PMID- 15259666
TI  - Monte Carlo calculation of the sensitivity of a commercial dose calibrator to
      gamma and beta radiation.
AB  - The detection process used in a commercial dose calibrator was modeled using the
      GEANT 3 Monte Carlo code. Dose calibrator efficiency for gamma and beta emitters,
      and the response to monoenergetic photons and electrons was calculated. The model
      shows that beta emitters below 2.5 MeV deposit energy indirectly in the detector
      through bremsstrahlung produced in the chamber wall or in the source itself.
      Higher energy beta emitters (E > 2.5 MeV) deposit energy directly in the chamber
      sensitive volume, and dose calibrator sensitivity increases abruptly for these
      radionuclides. The Monte Carlo calculations were compared with gamma and beta
      emitter measurements. The calculations show that the variation in dose calibrator
      efficiency with measuring conditions (source volume, container diameter,
      container wall thickness and material, position of the source within the
      calibrator) is relatively small and can be considered insignificant for routine
      measurement applications. However, dose calibrator efficiency depends strongly on
      the inner-wall thickness of the detector.

PMID- 15259667
TI  - Extended parallel backprojection for standard three-dimensional and phase
      correlated four-dimensional axial and spiral cone-beam CT with arbitrary pitch,
      arbitrary cone-angle, and 100% dose usage.
AB  - We have developed a new approximate Feldkamp-type algorithm that we call the
      extended parallel backprojection (EPBP). Its main features are a phase-weighted
      backprojection and a voxel-by-voxel 180 degrees normalization. The first feature
      ensures three-dimensional (3-D) and 4-D capabilities with one and the same
      algorithm; the second ensures 100% detector usage (each ray is accounted for).
      The algorithm was evaluated using simulated data of a thorax phantom and a
      cardiac motion phantom for scanners with up to 256 slices. Axial (circle and
      sequence) and spiral scan trajectories were investigated. The standard
      reconstructions (EPBPStd) are of high quality, even for as many as 256 slices.
      The cardiac reconstructions (EPBPCI) are of high quality as well and show no
      significant deterioration of objects even far off the center of rotation. Since
      EPBPCI uses the cardio interpolation (CI) phase weighting the temporal resolution
      is equivalent to that of the well-established single-slice and multislice cardiac
      approaches 180 degrees CI, 180 degrees MCI, and ASSRCI, respectively, and lies in
      the order of 50 to 100 ms for rotation times between 0.4 and 0.5 s. EPBP appears
      to fulfill all required demands. Especially the phase-correlated EPBP
      reconstruction of cardiac multiple circle scan data is of high interest, e.g.,
      for dynamic perfusion studies of the heart.

PMID- 15259668
TI  - Comment on "In vivo diode dosimetry for routine quality assurance in IMRT".

PMID- 15259669
TI  - Newly-formed axonal branches of rat sciatic neurons sprouting in the spinal cord
      after peripheral axotomy.
AB  - A retrograde method of nerve tracing using a recombinant adenovirus was applied
      to experimental regeneration of peripheral nerves to study the sprouting position
      of the regenerating axon. This enabled us to see the entire length of the axons
      on a whole-mount neural specimen. The peroneal nerve was transsected and infected
      with this virus, and the tibial nerve was transsected and sutured in eight Wistar
      rats. Four to five weeks later, labelled axons appeared in the tibial nerve, some
      of which could be traced from the tibial nerve to the spinal cord without making
      a connection with other labelled fibres. Control experiments negated the
      possibilities of transneuronal immigration or contamination of the virus. When
      the peroneal and tibial nerves were double-labelled with fluorescent tracers four
      weeks after their transsection, double-labelled motor neurons appeared. Based on
      these findings, we conclude that regenerating branches do sprout in the spinal
      cord after axotomy.

PMID- 15259670
TI  - Arterial anatomy of the lower lip.
AB  - The arterial anatomy of the lower lip was investigated in 12 sides of six fresh
      cadavers that had been injected systemically with a lead oxide and gelatin
      mixture. We found that the blood supply of the lower lip was derived from the
      facial artery and three dominant labial arteries: the inferior labial artery, the
      horizontal labiomental artery, and the vertical labiomental artery. The inferior
      labial artery was derived from the facial artery or superior labial artery, and
      ran through the submucous tissue horizontally. The horizontal labiomental artery
      arising from the facial artery was located between the depressor labii inferioris
      muscle and orbicularis oris muscle. The vertical labiomental artery arose from
      the submental artery. These three arteries provided small vessels that traversed
      vertically. These small vessels and the small branches of the facial artery, that
      run superficial and deep to the orbicularis oris muscle, formed a vascular
      network in subcutaneous and submucous tissues and minute vessels branched off to
      the skin, mucosa, and muscles.

PMID- 15259671
TI  - Treatment of paralytic lagophthalmos by loading the lid with a gold plate and
      lateral canthopexy.
AB  - Various methods of managing patients with lagophthalmos secondary to paralysis of
      the facial nerve have been reported. While addition of a gold plate facilitates
      displacement of the upper eyelid downwards, coaptation of the lid margin is often
      incomplete because of coexisting ectropion of the lower lid. The outcome
      obtainable from loading the lid with a gold plate alone is often unsatisfactory.
      To manage the deformity by combining the loading of the lid with gold plate and
      lateral canthopexy is technically simple. Morbidity is minimal as it can be done
      under local anaesthesia. Adequacy of coaption of the palpebral margin could be
      assessed immediately. We have managed a total of seven (mainly elderly) such
      patients between 1999 and 2000 in our hospitals. The outcome was generally
      satisfactory and there were no complications.

PMID- 15259672
TI  - Role of vascularised tissue transfer after oncological resection in the upper
      extremity.
AB  - We reviewed 12 patients who had had vascularised tissue transfer after
      oncological resection in the upper extremity. All patients had immediate
      reconstruction, and one had a double tissue transfer. Tissues used were skin
      flaps, free muscles, and vascularised fibulas, for resurfacing the wound, motor
      recovery, and reconstruction of large bony defects, respectively. All the
      patients returned early to their daily activities. Although local recurrences
      were encountered in two patients, they were again rendered disease-free by
      salvage operations. Two patients had secondary reconstructions using pedicle
      latissimus dorsi flaps for late problems, including one of the two patients who
      developed a local recurrence. The mean functional score using the system devised
      by the Musculoskeletal Tumor Society was 84%. All the upper extremities were
      successfully rescued with satisfactory function. Vascularised tissue transfer was
      invaluable for achieving both curative resection of the tumour and a useful upper
      extremity.

PMID- 15259673
TI  - Split skin graft reconstruction in vaginal agenesis: a long-term follow-up.
AB  - Fifteen women who had isolated congenital vaginal agenesis reconstructed by the
      split skin inlay grafting technique at a mean age of 19 (0.5) years, were
      followed up 2-33 years after the operation. The reconstruction had been
      functionally successful in all patients. No patient reported dyspareunia,
      exceptional dryness, or disturbing vaginal discharge. All the women had
      established normal, stable relationships with men. Their general recollection of
      the hospital stay and treatment was favourable. The importance of a thorough
      preoperative and postoperative explanation was emphasised by the patients, as
      well as their wish for long term contact with a specialist in gynaecology who was
      well aware of their special problems. In conclusion, the good functional results
      have been accompanied by stable social and psychological relationships.

PMID- 15259675
TI  - Total modular wrist prosthesis: a new design.
AB  - The common modes of failure of total wrist arthroplasty have been fracturing,
      loosening, pain on pronation and supination, and muscle soft-tissue imbalance. To
      overcome some of these problems a total modular wrist prosthesis has been
      designed for use both as a primary prosthesis and for revision surgery. An
      uncemented and cemented radial component, secure fixation in three metacarpal
      bones, and an unconstrained and constrained version account for the modularity,
      including optional treatment of the distal radioulnar joint. We present the
      design of the prosthesis including the preliminary clinical and radiographic
      results after a mean follow-up of 20 months in 32 patients of whom four have had
      earlier implants revised.

PMID- 15259674
TI  - Treatment of severe deformities of the toenails by the modified Zadik method with
      artificial skin.
AB  - A number of operations have been devised to treat ingrowing toenails and pincer
      nails, and they have given good aesthetic and functional results. However, there
      have been few reports of operations for the treatment of severe nail deformities
      caused by damage to the matrix of the nail by injury, or by inappropriate removal
      of the nail or intractable onychomycosis or cardiovascular or neurological
      disorders. In 1950, Zadik reported a radical technique for ingrown nails and
      pincer nails: after avulsion of the nail, the matrix was excised completely and
      the posterior nail wall was sutured to the nail bed as an advancement flap. We
      have treated 23 severe deformities other than ingrown nails and pincer nails in
      14 patients by the modified Zadik method with artificial skin. As a result,
      symptoms including pain were alleviated in all patients. The nail plate did not
      regenerate, and no patient had aesthetic complaints.

PMID- 15259676
TI  - Arthrodesis for chronic static scapholunate dissociation: a prospective study in
      12 patients.
AB  - Twelve patients had limited arthrodesis between the scaphoid and the lunate for
      chronic static scapholunate dissociation using internal plate osteosynthesis. The
      median time between the injury and surgery was 50 months (range 9-180). They were
      followed up for a year postoperatively. Preoperative symptoms were pain,
      functional impairment, and restricted movement. During operation the scapholunate
      interosseous ligament was completely torn and the scaphoid malrotated in all
      patients. The range of motion was measured preoperatively and postoperatively,
      and the unaffected side used for control. For all patients except one
      postoperative extension, flexion, and radial deviation had considerably
      decreased. However, supination increased in seven of 12 patients postoperatively
      and so did pronation in seven of 12 patients. One patient (case 12) had an
      improved range of motion postoperatively in all directions. The mean grip
      strength was 76% of the unaffected side preoperatively, and has increased to 85%
      postoperatively. We found that bone healing was rare and most arthrodeses healed
      by a fibrous union. We found no correlation with preoperative arthrosis and
      clinical outcome. One patient had retired from work before operation because of
      back pain and one because of age. Two patients had taken early retirement because
      of wrist pain, and one patient was still on sick-leave at the follow-up a year
      postoperatively. Five patients returned to full-time work and two patients to
      part-time work. Four patients were on long-term sick-leave preoperatively and
      three of them returned to their previous occupations. Analysis of the patients'
      subjective outcome (including pain and functional scores) showed overall
      satisfaction, and objective data show that scapholunate arthrodesis for chronic
      static scapholunate dissociation provides substantial improvement over the
      preoperative condition.

PMID- 15259677
TI  - Intramedullary bone cementing for the treatment of Colles fracture in elderly
      patients.
AB  - Eighteen patients with Colles fractures, mean age 70 years (range 55-91), were
      treated by intramedullary bone cementing. The best indication for this technique
      was an unstable extra-articular Colles fracture with osteoporosis. Bone cement
      was packed into the canal that was made by curettage of intramedullary cancellous
      bone from the dorsal fracture site. Intramedullary cementing caused little
      bleeding from the medullary canal and no irritation of the extensor tendons.
      Because of rigid fixation, patients could use the affected hand for light
      activities without any external orthosis the day after surgery. Cortical healing
      was seen in all cases within three months and there was no cement loosening or
      other complications during the mean 28 month (range 6-43) follow up period.
      Intramedullary bone cementing is one of the optimal treatments for Colles
      fractures in elderly patients.

PMID- 15259678
TI  - Three cases of successful microvascular ear replantation after bite avulsion
      injury.
AB  - We present three cases of sub-total amputation of the external ear caused by bite
      avulsion injury. The ears were all successfully replanted despite us being unable
      to perform a venous anastomosis in one case. These outcomes support attempted
      microsurgical replantation for total or sub-total amputations of the ear, as
      successful replantation is the most effective surgical option.

PMID- 15259679
TI  - Use of the SpaceMaker balloon dissector for repair of sacral pressure sores.
AB  - Most of the techniques that have been suggested for closure of sacral pressure
      sores use musculo-cutaneous flaps. We report our experience in three patients
      using the SpaceMaker balloon dissector. The dissector was inserted into the
      subgluteal maximus muscle plane to expand the muscle and overlying skin, thereby
      forming bilateral sliding and tension-free musculocutaneous flaps. The procedure
      is simple, safe, bloodless, and combines the advantages of advancement of a
      muscle flap and expansion.

PMID- 15259680
TI  - Use of an arterialised venous skin flap in the replantation of an amputated
      thumb.
AB  - We report the replantation of an amputated thumb using a venous skin flap,
      harvested from the volar surface of the forearm, to make up the soft tissue
      defect, and to restore the vascular continuity to the thumb.

PMID- 15259681
TI  - HIPAA: updates, problems, and reminders.

PMID- 15259682
TI  - Supply and demand: lessons learned at Toys "R" Us.

PMID- 15259683
TI  - HIS/RIS/PACS integration: getting to the gold standard.
AB  - The technology for acquiring, storing, retrieving, displaying, and distributing
      images has advanced dramatically in recent years. The push is toward enterprise
      wide image management solutions, where digital images from radiology, cardiology,
      and other "ologies" are seamlessly linked with information from clinical
      information systems and other databases, and they are accessed seamlessly from a
      single point of end-user interaction. The "gold standard" of system integration
      would provide the platform for improved workflow, patient throughput and patient
      safety, as well as decreased cost. Unfortunately, the gold standard remains
      elusive in most healthcare environments, even those with new systems. One of the
      earliest issues that plagued the progress of hospital information
      system/radiology information systems/picture archiving and communication systems
      (HIS/RIS/PACS) integration was a matter of language between Health Level-7 (HL7)
      and DICOM. This barrier was solved by the broker--a software and hardware device
      that accepts HL7 messages from the RIS then translates, or maps, the data to
      produce DICOM messages for transmission to the PACS. Technologist workflow
      requires patient and exam information from the RIS to flow to the modality. The
      broker provides support for this by taking advantage of the DICOM Modality
      Worklist (DMWL). Two primary problems are inherent in most brokered
      configurations. Workflow is driven by paper, and RIS information flows in 1
      direction only, which leads to duplicative databases. Overcoming the limitations
      of HIS/RIS/PACS connectivity requires industry accepted communication
      protocols/rules. To facilitate this, the Integrating the Health Care Enterprise
      (IHE) initiative was developed. The goal of IHE is to provide end-users improved
      access to critical patient and clinical information across all systems within the
      healthcare delivery network. While the IHE initiative began to facilitate more
      efficient, predictable, and functional integration between disparate systems,
      vendors still had technology hurdles to overcome. System integration continues to
      be significantly hampered, not by technology limitations, but instead by business
      and political issues. In response to these challenges, several vendors have begun
      to offer consolidated RIS/PACS solutions and/or HIS/RIS/PACS solutions.
      Consequently, the prospect of the gold standard appears to be on the horizon.
      Single vendor consolidated systems are not, however, feasible for deployment in
      many healthcare organizations, and they are not necessarily the panacea.

PMID- 15259684
TI  - Integrating digital systems: commitment and collaboration.
AB  - One year ago, the radiology department at Ball Memorial Hospital, a 350-bed
      facility in Muncie, IN, was completely film-based. The need to support a new all
      digital, 35-room emergency department (ED) hastened the facility's transition to
      a digital environment. Today, with the exception of mammography, the hospital's
      imaging services are now digital. To develop and implement the project, the
      hospital formed an internal implementation team. An independent consultant was
      also hired to evaluate the impact of these new technologies and to provide an
      estimated cost payback. After research, site visits, and vendor demonstrations,
      the hospital selected a single vendor for its picture archiving and communication
      system (PACS), digital radiography (DR), computed radiography (CR), and overall
      project management. The DR system was installed in the ED to provide digital
      image capture for a full range of trauma exams. The ED also initially began
      utilizing a Web-based PACS distribution originally implemented for after-hours
      teleradiology. The majority of the hospital's imaging studies are captured with 2
      multi-cassette CR systems that serve 7 exam rooms in the radiology department.
      The hospital also installed remote operations panels to expedite entry of patient
      and exam information. Technologists readily embraced both CR and DR systems. The
      Web distribution system now transmits images to hospital-based computers and to
      150 remote referring physicians. The PACS platform automatically e-mails key
      images and radiology reports to referring physicians. Authorized physicians can
      also request reports and images on an as-needed basis. The PACS vendor had
      previously performed multiple integrations with the radiology information system
      (RIS) vendor; the integration of PACS and RIS was extremely smooth. One of the
      critical components of a successful conversion is experienced, dedicated
      management. The hospital retained professional project management services to
      facilitate implementation and to ensure adequate training for all users.

PMID- 15259685
TI  - Paperless medical records: reinventing the patient experience.
AB  - At North Shore Magnetic Imaging Center, the patient paper medical record system
      was becoming very cumbersome, and it served as a source of frustration for
      everyone involved: patients, technologists, radiologists, and staff members. The
      center's mapping of a typical patient experience indicated that, from the initial
      phone call scheduling an exam to a completed visit (claim processed and payment
      received), a record could be handled by as many as 20 sets of hands! In June
      2002, the center's growth and a concern that patients were losing a one-on-one
      experience with the medical staff led to an evaluation of workflow processes
      existing at that time. The evaluation began with a survey of staff members,
      center management, radiologists, and referring physicians. Their responses
      indicated 3 common themes: stress, overload, and frustration over systems in
      place. Comments from the survey were grouped into 3 areas: Continue to Do, Stop
      Doing, and Start Doing. The Start Doing responses provided solid objectives. The
      center set out to establish a breakthrough project that included all stakeholders
      -patients, staff, management, and radiologists. The Reinvention Project had 2
      primary goals: move to a paperless environment and increase the level of patient
      care. The project was divided into internal and external teams. The internal
      team, called the Reinvention Team, was responsible for the actual hands-on
      aspects of the process. There were numerous external teams; each had defined
      roles and specific outcomes for achievement. The external teams' responsibilities
      included implementing an Internet protocol telephone system; researching voice
      recognition; restructuring job descriptions, training manuals, and performance
      evaluations; and conducting a patient-centered focus group.

PMID- 15259686
TI  - PACS--and beyond. A journey to the digital promised land.
AB  - A successful picture archiving and communication system (PACS) integration
      depends on much more than the technology; marketing also plays a large role. This
      fact was evident from the inception of the PACS project at Boca Raton Community
      Hospital (BRCH). Strategic and effective marketing efforts should target
      technologists, nurses, physicians (including radiologists), administration, and
      colleagues in other departments. The buy-in of these users is critical to the
      project's success. BRCH's first marketing effort took place during the initial
      PACS presentation made to the hospital's board of directors. Once approval was
      given and a 6-month implementation target was set, a strategic and effective
      marketing/education plan commenced. Posters, brochures, t-shirts, and promotional
      items were distributed in a coordinated effort to target hospital staff and
      referring physician offices. Through its "Got PACS?" branding and other identity
      materials, BRCH implemented a marketing plan that informed, educated, and engaged
      PACS users.

PMID- 15259687
TI  - The future is now....

PMID- 15259688
TI  - New guidance criteria for central venous catheters.

PMID- 15259689
TI  - Finances: keeping a watchful eye on business.

PMID- 15259690
TI  - Conflict resolution in healthcare management.
AB  - Conflict causes decided tension in the workplace and often produces poor
      professional outcomes. A manager dealing with conflict can experience a crisis of
      confidence and often ends up second-guessing himself or herself, regardless of
      how a situation has been handled. In some organizations, conflict is not viewed
      positively or as an opportunity for improvement. In these organizations, most
      individuals will see conflict as being unproductive, unpleasant, and a waste of
      time and energy. Yet, conflict provides employees with critical feedback on how
      things are going. When viewed in a positive context, even personality conflicts
      may provide information to the healthcare manager about what is not working in
      the organization. If conflict is not directed and controlled, it can have
      damaging effects in the workplace, stifling the growth of departments and
      deflating employee morale. Our job as healthcare managers is to deal with
      conflict so that it does not decrease productivity or detract from the provision
      of patient-centered care. There are 4 general sources for interpersonal conflict:
      personal differences, informational deficiency, role incompatibility, and
      environmental stress. There are 5 common responses used in dealing with conflict:
      forcing, accommodating, avoiding, compromising, and collaborating. Healthcare
      managers should become comfortable with using all of these approaches.

PMID- 15259691
TI  - Developing and building relationships with referring physicians.

PMID- 15259692
TI  - AHRA publishes updated Compensation & Benefits Survey.

PMID- 15259693
TI  - Schizo-ville.

PMID- 15259694
TI  - A differentiated assessment of the future of biotechnology. A perspective from an
      EU member state.

PMID- 15259695
TI  - TCDD biomonitoring and exposure to Agent Orange: still the gold standard.

PMID- 15259696
TI  - Formation and emission of chloroanisoles as indoor pollutants.
AB  - GOAL, SCOPE AND BACKGROUND: Complaints by residents of frame-houses about musty
      odour in the houses has become an increasing problem within the last years. An
      additional problem is that the odour is transferred to clothes and skin. The
      persons themselves do not recognize the smell after a while because of
      adaptation. Serious social problems are the result. For a long time, the smell
      was explained to be from mould due to construction-based humidity problems.
      However, in an increasing number of houses, no indications were found for
      elevated levels of mould growth. METHODS: Air and material samples were taken
      from 5 houses, which show typical musty odours, and analysed with respect to
      chlorophenols and chloroanisoles. Additionally, some samples were analysed for
      lindane and its metabolites, because lindane was commonly used together with
      pentachlorophenol (PCP) for wood protection. RESULTS AND DISCUSSION: Meticulous
      analysis resulted in the identification of chloroanisoles, mainly 2,3,4,6
      tetrachloroanisole. These substances are known from corky wines and from
      contamination of food from pentachlorophenol (PCP) treated pallets and result
      from microbiological metabolic processes. Pentachlorophenol was commonly used to
      protect wood from fungi in Germany mainly in the later 60s and 70s. Details of
      these processes, as well as effective methods to identify chloroanisoles in the
      problem houses, are described. CONCLUSIONS: Chloroanisoles formed by metabolism
      of PCP have been well known to contaminate food or wine. Here, they were
      identified and are probably responsible for the musty odours in the frame houses.
      Since it is quite clear that these substances were not components of building
      materials used in the houses, an explanation for chloroanisole formation is
      proposed. Localized dampness probably favours microbial growth associated with
      metabolic conversion of chlorophenols to the corresponding chloroanisoles,
      primarily 2,3,4,6-tetrachloroanisol, which spread throughout the buildings,
      resulting in the observed odours. RECOMMENDATIONS AND OUTLOOK: The group of
      chloroanisoles has been recognized as important indoor pollutants as they possess
      musty odours at extremely low concentrations, e.g. for 2,4,6-trichloroanisole in
      a range of 5-10 ppt in air (Staples 2000). On the basis of currently available
      toxicological data, exposure of the occupants to the concentrations of
      chloroanisoles measured is not associated with a health risk. No correlation
      could be observed between concentrations of chloroanisoles and PCP in house dust
      and indoor air. However, chloroanisoles are good indicators for possible PCP
      treatment of wood in frame houses and their detection should initiate
      investigations on PCP contamination. Research is continuing to identify the
      microorganisms involved and to devise a remediation procedure for affected
      houses.

PMID- 15259697
TI  - (M)VOC and composting facilities. Part 2: (M)VOC dispersal in the environment.
AB  - BACKGROUND, AIMS AND SCOPE: Composting facilities are known to release odorous
      volatiles due to biodegradation of municipal waste and plant residues. Although
      odour perception and its grading is influenced by experience, attitude and
      adaptation, these emissions have created a lack of acceptance for residents in
      the vicinity of composting facilities. Enclosure of compost pile halls,
      ventilation systems and biofilters are often insufficient to minimise the burden
      of compost-derived compounds in the air. Moreover, economic considerations forced
      smaller communities to establish less sophisticated facilities with open storage
      areas and other relevant sources for wind-borne dispersal of bioaerosols. Aim of
      the present study was to characterise the immission and dispersal of microbial
      volatiles (MVOC) and, besides, to find coincidences between MVOC and compost
      odour. METHODS: In the course of this study, the surroundings of two composting
      facilities, differing in their type of process engineering, were investigated for
      emission of volatiles in the environment. Both microbially and plant-derived
      substances were assessed, several of which have low odour thresholds. Air samples
      were taken in distances ranging from 50 to 800 m in a downwind direction from
      each facility. RESULTS AND DISCUSSION: Compost-derived and microbial volatile
      organic compounds (MVOC) were found at distances of up to 800 m from the
      composting facilities. Terpenes like alpha-pinene, camphene and camphor were the
      dominant compounds and coincided with typical compost odour, whereas several
      typical MVOC were not found at greater distances. The terpenes in combination
      with certain MVOC may play an important role in the perception of compost odour.
      Exposure concentrations were not of toxicological relevance, but sensory
      irritation and psychohygienic effects due to an annoyance potential of such
      compounds should not be dismissed. RECOMMENDATIONS AND OUTLOOK: Although terpenes
      are generally associated with pleasant odour characteristics, they seemed to
      contribute to malodours in a mixture with other VOC, in this context of volatile
      waste from compost facilities. Malodorous emissions from biowaste have to be
      considered as sources of health complaints and the investigation of mixtures of
      compost-derived volatiles is still inevitable. Exposure levels have to be
      discussed taking VOC mixtures into account. Within composting facilities,
      technical devices have to be improved to minimise dispersal of volatiles to
      prevent residents from immissions eventually causing health complaints.

PMID- 15259698
TI  - First assessment of the PM10 and PM2.5 particulate level in the ambient air of
      Belgrade city.
AB  - INTENTION, GOAL, SCOPE, BACKGROUND: As the strong negative health effect of
      exposure to the inhalable particulate matter PM10 in the urban environment has
      been confirmed, the study of the mass concentrations, physico-chemical
      characteristics, sources, as well as spatial and temporal variation of
      atmospheric aerosol particles becomes very important. OBJECTIVE: This work is a
      pilot study to assess the concentration level of ambient suspended particulate
      matter, with an aerodynamic diameter of less than 10 microm, in the Belgrade
      central urban area. Average daily concentrations of PM10 and PM2.5 have been
      measured at three representative points in the city between June 2002 and
      December 2002. The influence of meteorological parameters on PM10 and PM2.5
      concentrations was analyzed, and possible pollution sources were identified.
      METHODS: Suspended particles were collected on Pure Teflon filters by using a
      Mini-Vol low-volume air sampler (Airmetrics Co., Inc.; 5 l min(-1) flow rate).
      Particle mass was determined gravimetrically after 48 h of conditioning in a
      desiccator, in a Class 100 clean room at the temperature T = 20 degrees C and at
      about 50% constant relative humidity (RH). RESULTS AND DISCUSSION: Analysis of
      the PM10 data indicated a marked difference between season without heating-
      (summer; mean value 56 microg m(-3)) and heating season--(winter; mean value 96
      microg m3); 62% of samples exceeded the level of 50 microg m(-3). The impact of
      meteorological factors on PM concentrations was not immediately apparent, but
      there was a significant negative correlation with the wind speed. CONCLUSIONS:
      The PM10 and PM2.5 mass concentrations in the Belgrade urban area had high
      average values (77 microg m(-3) and 61 microg m(-3)) in comparison with other
      European cities. The main sources of particulate matter were traffic emission,
      road dust resuspension, and individual heating emissions. When the air masses are
      coming from the SW direction, the contribution from the Obrenovac power plants is
      evident. During days of exceptionally severe pollution, in both summer and winter
      periods, high production of secondary aerosols occurred, as can be seen from an
      increase in PM2.5 in respect to PM10 mass concentration. RECOMMENDATION AND
      OUTLOOK: The results obtained gave us the first impression of the concentration
      level of particulate matter, with an aerodynamic diameter of less than 10 microm,
      in the Belgrade ambient air. Due to measured high PM mass concentrations, it is
      obvious that it would be very difficult to meet the EU standards (EEC 1999) by
      2010. It is necessary to continue with PM10 and PM2.5 sampling; and after
      comprehensive analysis which includes the results of chemical and physical
      characterization of particles, we will be able to recommend effective control
      measures in order to improve air quality in Belgrade.

PMID- 15259699
TI  - Sensitivity analyses of woody species exposed to air pollution based on
      ecophysiological measurements.
AB  - GOAL, SCOPE AND BACKGROUND: Air pollution has been of a major problem in the
      Pearl River Delta of south China, particularly during the last two decades.
      Emissions of air pollutants from industries have already led to damages in
      natural communities and environments in a wide range of the Delta area. Leaf
      parameters such as chlorophyll fluorescence, leaf area (LA), dry weight (DW) and
      leaf mass per area (LMA) had once been used as specific indexes of environmental
      stress. This study aims to determine in situ if the daily variation of
      chlorophyll fluorescence and other ecophysiological parameters in five seedlings
      of three woody species, Ilex rotunda, Ficus microcarpa and Machilus chinensis,
      could be used alone or in combination with other measurements for sensitivity
      indexes to make diagnoses under air pollution stress and, hence, to choose the
      correct tree species for urban afforestation in the Delta area. METHODS: Five
      seedlings of each species were transplanted in pot containers after their
      acclimation under shadowing conditions. Chlorophyll fluorescence measurements
      were made in situ by a portable fluorometer (OS-30, Opti-sciences, U.S.A). Ten
      random samples of leaves were picked from each species for LA measurements by
      area-meter (CI-203, CID, Inc., U.S.A). DW was determined after the leaf samples
      were dried to a constant weight at 65 degrees C. LMA was calculated as the ratio
      of DW/LA. Leaf N content was analyzed according to the Kjeldhal method, and the
      extraction of pigments was carried out according Lin et al. RESULTS AND
      DISCUSSION: The daily mean Fv/Fm (Fv is the variable fluorescence and Fm is the
      maximum fluorescence) analysis showed that Ilex rotunda and Ficus microcarpa were
      more highly resistant to pollution stress, followed by Machilus chinensis,
      implying that the efficiency of photosystem II in I. rotunda was less affected by
      air pollutants than the other two species. Little difference in daily change of
      Fv/Fm in I. rotunda between the polluted and the clean site was also observed.
      However, a relatively large variation of Fv/Fm appeared in the other two species,
      particularly in M. chinensis, suggesting that they were more sensitive to air
      pollutants than I. rotunda. The mean LA was reduced for all species growing at
      the polluted site. The mean LMA for all species exceeded the sclerophylly
      threshold given by Cowling and Campbell and increased for those under pollution
      stress, which could be explained as one of the acclimation strategies for plants
      to air pollution stress. Little difference in leaf chlorophyll content was
      observed in F. microcarpa and M. chinensis, while remarkable differences were
      found in I. rotunda growing at the polluted and the clean site. Content of leaf
      carotenoids was largely reduced in I. rotunda growing at the polluted site, but
      increased in F. microcarpa and M. chinensis, compared with plants growing at the
      clean site. Plants growing at the clean site had a lower leaf N content than
      those growing at the polluted site. In addition, species with a higher resistance
      to pollution stress showed less difference in leaf N content than those sensitive
      species. CONCLUSION: Based on Fv/Fm measurements of the three woody species, I.
      rotunda showed the highest resistance to air pollutants from ceramic industries,
      followed by F. microcarpa. M. chinensis was the most sensitive species to air
      pollution, had lowest capacities to cope with the air pollution stress, which was
      consistent with visual injury symptoms observed in the crown profiles of plants
      at the polluted site. Fv/Fm, LAM, LA, leaf pigments and N content could be used
      alone or in combination to diagnose the extent of the physiological injury. The
      ratio of Fv/Fm, however, was the best and most effective parameter.
      RECOMMENDATION AND OUTLOOK: Tree species which have higher air-pollutant
      resistance, as diagnosed by such ecophysiological parameters, should be
      considered first and planted widely for urban afforestation or forest
      regeneration in areas where the forest was seriously degraded or forest health
      was markedly effected by the same kind of air pollutants.

PMID- 15259700
TI  - Modelling critical levels of ozone for the forested area of Austria.
      Modifications of the AOT40 concept.
AB  - GOAL, SCOPE AND BACKGROUND: Ozone is the most important air pollutant in Europe
      for forest ecosystems and the increase in the last decades is significant. The
      ozone impact on forests can be calculated and mapped based on the provisional
      European Critical Level (AOT40 = accumulated exposure over a threshold of 40 ppb,
      10,000 ppb x h for 6 months of one growing season calculated for 24 h day(-1)).
      For Norway spruce, the Austrian main tree species, the ozone risk was assessed in
      a basis approach and because the calculations do not reflect the health status of
      forests in Austria, the AOT40 concept was developed. METHODS: Three approaches
      were outlined and maps were generated for Norway spruce forests covering the
      entire area of Austria. The 1st approach modifies the AOT40 due to the assumption
      that forests have adapted to the pre-industrial levels of ozone, which increase
      with altitude (AOTalt). The 2nd approach modifies the AOT40 according to the
      ozone concentration in the sub-stomata cavity. This approach is based on such
      factors as light intensity and water vapour saturation deficit, which affect
      stomatal uptake (AOTsto). The 3rd approach combines both approaches and includes
      the hemeroby. The pre-industrial ozone level approach was applied for
      autochthonous ('natural') forest areas, the ozone-uptake approach for non
      autochthonous ('altered') forest areas. RESULTS AND DISCUSSION: The provisional
      Critical Level (AOT40) was established to allow a uniform assessment of the ozone
      risk for forested areas in Europe. In Austria, where ozone risk is assessed with
      utmost accuracy due to the dense grid of monitoring plots of the Forest Inventory
      and because the continuously collected data from more than 100 air quality
      measuring stations, an exceedance up to the five fold of the Critical Level was
      found. The result could lead to a yield loss of up to 30-40% and to a severe
      deterioration in the forest health status. However, the data of the Austrian
      Forest Inventory and the Austrian Forest Damage Monitoring System do not reflect
      such an ozone impact. Therefore, various approaches were outlined including the
      tolerance and avoidance mechanisms of Norway spruce against ozone impact. Taking
      into consideration the adaptation of forests to the pre-industrial background
      level of ozone, the AOT40 exceedances are markedly reduced (1st approach). Taking
      into account the stomatal uptake of ozone, unrealistic high amounts of
      exceedances up to 10,000 ppb x h were found. The modelled risk does not
      correspond with the health status and the wood increment of the Austrian forests
      (2nd approach). Consolidating the forgoing two approaches, a final map including
      the hemeroby was generated. It became clear that the less natural ('altered')
      forested regions are highly polluted. This means, that more than half of the
      spruce forests are endangered by ozone impact and AOT40 values of up to 30,000
      ppb x h occur (3rd approach). CONCLUSIONS: The approaches revealed that a
      plausible result concerning the ozone impact on spruce forests in Austria could
      only be reached by combining pre-industrial ozone levels, ozone flux into the
      spruce needles and the hemeroby of forests.

PMID- 15259701
TI  - Photodegradation of polychlorinated dibenzo-p-dioxins and dibenzofurans in soil
      with vegetable oil.
AB  - GOAL, SCOPE AND BACKGROUND: This study was carried out to investigate the effect
      of olive oil on the photodegradation of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) in contaminated sawmill soil. Previous studies had shown
      that the solubility of PCDD/Fs in olive oil is high and a rapid photodegradation
      of PCDD/Fs takes place in olive oil when irradiated with ultraviolet (blacklight)
      lamps. The efficiency of this treatment method was evaluated under more practical
      conditions. These included the use of sunlight irradiation and a lower-grade
      olive oil, without a preliminary extraction of soil with olive oil. METHODS: A 1
      cm layer of contaminated sawmill soil was blended with 20 weight-% of olive oil
      and exposed to sunlight for four weeks. In another experiment, a new dose of
      olive oil was added at the middle of the exposure period. The PCDD/F
      concentrations of the soils were monitored periodically. RESULTS AND DISCUSSION:
      A reduction in the concentration of 2,3,7,8-chlorinated PCDD/Fs by 59% and in WHO
      TEQ in contaminated sawmill soil by 48% was attained after blending the soil with
      two doses (20 + 20%) of olive oil and exposing the mixture to sunlight for four
      weeks. Photodegradation with only one dose of olive oil was less efficient. This
      suggests that periodical additions of olive oil would be needed to maintain a
      proper degradation rate. After the oil additions, the WHO-TEQ content of the soil
      declined with first order reaction half-lives of 19.2 to 19.7 d. The overall half
      life during the four-week treatment, however, was 30 d. CONCLUSION: A significant
      reduction in the PCDD/F concentration of aged sawmill soil can be achieved with a
      relatively simple olive oil-sunlight treatment. RECOMMENDATIONS AND OUTLOOK: Some
      theoretical and technological questions need to be solved before using the
      investigated soil decontamination method in larger-scale applications. The
      functions of vegetable oils in photodegradation processes should be studied in
      more detail. The amount of oil that is needed for a proper solubilisation and
      photodegradation of PCDD/Fs should be minimised. Moreover, special care should be
      taken to prevent mobilisation of PCDD/Fs to the surrounding environment and to
      avoid leaving bioavailable residuals of PCDD/Fs in soil.

PMID- 15259702
TI  - Chlorinated dibenzo-p-dioxins and dibenzofurans in the Baltic herring and sprat
      of Estonian coastal waters.
AB  - BACKGROUND, AIMS AND SCOPE: The concentration of chlorinated dibenzo-p-dioxins
      and dibenzofurans in many fish from the Baltic requires monitoring, since it
      approaches or exceeds the European Union threshold limit value of 4 pg TEQ/g wet
      weight of fish for human consumption. The concentrations, expressed in TEQs, are
      important for toxicology and regulations, but hide the concentrations of the
      individual congeners, which are important for other environmental sciences,
      source allocation, and for the detection of measurement errors. This report
      evaluates the results of a survey reported earlier only in the terms of the TEQ
      concentrations. METHODS: Principal Component Analysis (PCA) was used to reduce
      the dimensions of the data (17 = 7 chlorinated dibenzo-p-dioxin and 10
      chlorinated dibenzofuran congeners) to three principal components. This
      facilitated the interpretation of the congener profiles. Slopes of the congener
      concentrations as a function of age of the fish were estimated by least squares
      regression. The results were compared with a large set of data for lake trout
      from Lake Ontario. RESULTS AND DISCUSSION: The congener profiles of Baltic
      herring are less scattered than those of sprat. The profiles of herring from the
      central Baltic differ from those of herring from the Gulf of Riga and both appear
      to be affected relatively minimally by the age of the fish. The congener profiles
      of herring from the western Gulf of Finland are similar to those from the central
      Baltic, those from middle Gulf of Finland are similar to those from the Gulf of
      Riga. Both seem to be more affected by age of the fish than the profiles of the
      first two groups. The concentrations of several pentachloro- and hexachloro
      dibenzo-p-dioxins and dibenzofurans increase with the age of the fish CONCLUSION:
      PCA is a good technique for the evaluation of the congener profiles. The
      resulting loading and score plots provide a good graphic summary of the
      multidimensional data. Additional analyses are needed to confirm the observed
      profile patterns. A comparison with the results of a long-term monitoring from
      another area shows that the age of the fish is a more important factor than the
      year of capture. RECOMMENDATION AND OUTLOOK: The surveys should continue for a
      number of years and the results should be presented and evaluated both in terms
      of the TEQs as well as in terms of weight concentrations. Since the
      concentrations do not appear to change very much from year to year, it would be
      better to carry out surveys only every 3-4 years and, instead, stratify the
      sampling according to age and gender of the fish, and to analyze replicate
      extracts by replicate measurements. The inclusion of unmarked replicate samples
      would be a good quality assurance measure. It would be desirable to analyze
      additional parts of the food chain in order to understand the fate of the
      compounds in the ecosystem.

PMID- 15259704
TI  - The World Congress on Industrial Biotechnology and Bioprocessing. Orlando,
      Florida, USA, April 21-23, 2004.

PMID- 15259705
TI  - Miniature lamellar grating interferometer based on silicon technology.
AB  - We present a lamellar grating interferometer realized with microelectromechanical
      system technology. It is used as a time-scanning Fourier-transform spectrometer.
      The motion is carried out by an electrostatic comb drive actuator fabricated by
      silicon micromachining, particularly by silicon-on-insulator technology. For the
      first time to our knowledge, we measure the spectrum of an extended white-light
      source with a resolution of 1.6 nm at a wavelength of 400 nm and of 5.5 nm at 800
      nm. The wavelength accuracy is better than 0.5 nm, and the inspected wavelength
      range extends from 380 to 1100 nm. The optical path difference maximum is 145
      microm. The dimensions of the device are 5 mm x 5 mm.

PMID- 15259703
TI  - Significance of platinum group metals emitted from automobile exhaust gas
      converters for the biosphere.
AB  - INTENTION, GOAL, SCOPE, BACKGROUND: Following the introduction of automobile
      catalytic converters the platinum group metals (PGM) platinum (Pt), palladium
      (Pd) and rhodium (Rh) gain on increasing interest in environmental research as
      these metals are emitted with exhaust fumes into the environment. Consequently,
      elevated PGM levels were found in different environmental matrices such as road
      dusts, soils along heavily frequented roads, sediments of urban rivers etc.
      Accordingly, the effects of increasing PGM emissions on the biosphere are
      controversially discussed. OBJECTIVE: This paper summarizes the present knowledge
      on the biological availability of PGM to plants and animals. As biological
      availability is one of the most decisive factors determining the toxicological
      potential of xenobiotics, this information is very important to evaluate the
      possible threat of the noble metals to ecosystems. RESULTS AND DISCUSSION: The
      availability of soluble as well as particle bound PGM to terrestrial plants was
      demonstrated in several studies. Experimental investigations revealed uptake of
      Pt, Pd and Rh also by aquatic plants. Additionally, the biological availability
      of the noble metals for animals has been verified in experimental studies using
      soluble metal salts, catalytic converter model substances, sediments of urban
      rivers, road dust or tunnel dust as metal sources. These studies refer mainly to
      aquatic animals. Beside of free living organisms, in particular worms
      parasitizing fish demonstrated a high potential to accumulate PGM. This could be
      of great interest in respect of biomonitoring purposes. Generally, for plants as
      well as for animals Pd turns out to be the best available metal among the PGM.
      Compared to other heavy metals, the biological availability of PGM from road dust
      to zebra mussels (Dreissena polymorpha) ranged between that of Cd and Pb.
      CONCLUSION: Especially chronic effects of PGM on the biosphere can not be
      excluded due to (1) their cumulative increase in the environment, (2) their
      unexpected high biological availability and bioaccumulation and (3) their unknown
      toxicological and ecotoxicological potential. However, it appears that acute
      effects on ecosystems due to anthropogenic PGM emission are not likely.
      RECOMMENDATION AND OUTLOOK: Research on environmental PGM contamination of the
      biosphere, especially the fauna, and on long-term toxicity of low PGM
      concentrations is highly appreciated. These studies require very sensitive
      analytical techniques to determine PGM even in low sample amounts. Research has
      to be done in particular on reliable determination of (ultra) trace levels of Pd
      and Rh as the lack of data on these two metals is mainly due to analytical
      problems.

PMID- 15259706
TI  - Fabric inspection by near-infrared machine vision.
AB  - Fabrics that have superstructures of colored squares, bands, etc., superimposed
      upon the basic web structure can be advantageously analyzed by use of near
      infrared (NIR) illumination and a conventional monochrome camera. The reduction
      in contrast of the superstructure signal in the NIR image facilitates inspection
      of the fabric's structure and defect segmentation. Underdetection and
      misdetection errors are noticeably reduced. This inspection takes advantage of
      the residual sensitivity of a monochrome camera, which can reach 1000 nm. The
      light source is an array of NIR LEDs emitting in a band to which the camera is
      still sensitive. NIR visual inspection can be performed by machines or by humans.
      In the latter case the observer looks at the NIR image of the fabric displayed on
      a TV monitor.

PMID- 15259707
TI  - Polarizing binary diffraction grating beam splitter.
AB  - We report a polarizing beam splitter that uses binary phase gratings written onto
      a liquid-crystal spatial light modulator. These gratings produce several linearly
      polarized diffracted orders and a zeroth-order beam whose polarization state can
      be completely controlled. Experimental results are shown.

PMID- 15259708
TI  - Bessel X waves in two- and three-dimensional bidispersive optical systems.
AB  - We show that new families of two- and three-dimensional nondiffracting Bessel X
      waves are possible in linear bidispersive optical systems. These X waves can be
      observed in both bulk and waveguide configurations as well as in photonic crystal
      lattices that simultaneously exhibit normal and anomalous dispersive-diffractive
      properties in different spatial or spatiotemporal coordinates.

PMID- 15259709
TI  - Efficient single-photon counting at 1.55 microm by means of frequency
      upconversion.
AB  - We demonstrate efficient single-photon detection at 1.55 microm by means of sum
      frequency mixing with a strong pump at 1.064 microm in periodically poled lithium
      niobate followed by photon counting in the visible region. This scheme offers
      significant advantages over existing InGaAs photon counters: continuous-wave
      operation, higher detection efficiency, higher counting rates, and no
      afterpulsing. We achieved single-photon upconversion efficiency of 90% at 21.6 W
      of circulating power in a resonant pump cavity with a 400-mW Nd:YAG laser. We
      observed high background counts at strong circulating pump powers due to
      efficient upconversion of pump-induced fluorescence photons.

PMID- 15259710
TI  - Frequency-resolving spatiotemporal wave-front sensor.
AB  - We report on a high-resolution wave-front sensor that measures the complete
      spatial profile of any frequency component of a laser field containing multiple
      frequencies. This probe technique was developed to address the necessity of
      measuring the spatial overlap of the carrier field with each sideband component
      of the field exiting the output port of a gravitational-wave interferometer. We
      present the results of an experimental test of the probe, where we were able to
      construct the spatial profile of a single radio-frequency sideband at the level
      of -50 dBc.

PMID- 15259711
TI  - Intercomparison of monochromatic source facilities for the determination of the
      relative spectral response of erythemal broadband filter radiometers.
AB  - The relative spectral responses of erythemally weighted broadband radiometers
      determined at three different laboratories are compared, and the systems are
      described. The results of measurements of four different broadband radiometers
      are discussed. Although the common dynamic range of the measured relative
      spectral responses is approximately 10(4), the differences in the relative
      spectral response functions are lower than 20%. These differences are related
      mostly to measurement uncertainties and differences in the spectral response
      facilities.

PMID- 15259712
TI  - Multiple-beam interference patterns in optical fiber generated with ultrafast
      pulses and a phase mask.
AB  - We compare the cladding patterns present in grating structures fabricated with an
      ultrafast laser and a phase mask with a cw beam interference model. We find that
      the observed patterns agree well with the model results for picosecond pulses;
      however, for femtosecond pulses, we show that the full bandwidth and the pulsed
      nature of the sources must be considered because the pattern can be affected by
      group-velocity walk-off. An interesting consequence of order walk-off is the
      possibility of pure two-beam interference generation with a phase mask in the
      femtosecond pulse regime.

PMID- 15259713
TI  - Pulse collisions in the stretched-pulse fiber laser.
AB  - We report the observation of a new regime of operation in the stretched-pulse
      fiber laser in which two groups of bound pulses travel in the cavity at different
      velocities. The pulse groups collide periodically and remain apparently unaltered
      after the collisions. The observed group-velocity difference is shown to exhibit
      a strong dependence on the time interval between the pulses in each bound state.

PMID- 15259714
TI  - Fabrication of helical long-period fiber gratings by use of a CO2 laser.
AB  - We present a method of helical long-period fiber grating (H-LPFG) fabrication by
      use of a CO2 laser for use as an optical torque sensor. A conventional optical
      fiber grating has periodic vertical index changes along its fiber axis, but a H
      LPFG has a screw-type index modulation. The helical index modulation is obtained
      with the asymmetric index change caused by a single-side laser beam exposure. The
      H-LPFG shows peak shifts with codirectional or contradirectional torsion to the
      helix. Also, the polarization-dependent loss is measured to be relatively small
      compared with that of a conventional long-period fiber grating.

PMID- 15259715
TI  - Technique for referencing of fiber-optic intensity-modulated sensors by use of
      counterpropagating signals.
AB  - We present a new all-optical fiber-referencing scheme for intensity-modulated
      sensors. It consists of a closed loop traversed by sensing and reference optical
      signals in opposite directions. With the proposed scheme the noise induced by
      power fluctuations of the optical source and mechanical perturbations can be
      greatly reduced. We experimentally demonstrate the efficiency of the scheme and
      discuss its use in a sensor array.

PMID- 15259716
TI  - Multiwavelength pulse generator using time-lens compression.
AB  - We demonstrate a novel method of generating a multiwavelength pulse train by use
      of time-lens compression. In addition to pulse compression, this time lens
      simultaneously displaces the pulses according to their center wavelengths,
      resulting in a temporally evenly spaced multiwavelength pulse train. We further
      demonstrate a new aberration-correction technique based on the temporal analog of
      a spatial correction lens to improve the quality of the compressed pulses.
      Through the use of cw distributed-feedback lasers and electro-optic phase
      modulators, the all-fiber system allows complete tunability of temporal spacing,
      spectral profile, and repetition rate.

PMID- 15259717
TI  - Accurate sensitivity in optically preamplified direct detection.
AB  - We present a novel model for calculating the bit error rate in optical
      communication systems in the case of on-off keying intensity modulation and
      optically preamplified direct detection. The model accounts for the intersymbol
      interference and is based on the Laguerre photon-count probability distribution
      predicted by photodetection theory. For a non-return-to-zero modulation format an
      accurate value of the sensitivity for a quantum-limited receiver of 33.9
      photons/bit is obtained.

PMID- 15259718
TI  - Random-hole optical fiber evanescent-wave gas sensing.
AB  - Research on development of optical gas sensors based on evanescent-wave
      absorption in random-hole optical fibers is described. A process to produce
      random-hole optical fibers was recently developed that uses a novel in situ
      bubble formation technique. Gas molecules that exhibit characteristic vibrational
      absorption lines in the near-IR region that correspond to the transmission window
      for silica optical fiber have been detected through the evanescent field of the
      guided mode in the pore region. The presence of the gas molecules in the holes of
      the fiber appears as a loss at wavelengths that are characteristic of the
      particular gas species present in the holes. An experimental setup was
      constructed with these holey fibers for detection of acetylene gas. The results
      clearly demonstrate the characteristic absorptions in the optical spectra that
      correspond to the narrow-line absorptions of the acetylene gas, and this
      represents what is to our knowledge the first report of random-hole fiber gas
      sensing in the literature.

PMID- 15259719
TI  - Hollow Bragg fiber bundles: when coupling helps and when it hurts.
AB  - Coupling between leaky modes of collinear hollow-core Bragg fibers is considered.
      It is found that coupling is unusually strong because of resonant effects in the
      interfiber cavity when the fibers are touching each other and decreases
      dramatically with the first tens of nanometers of fiber separation. However,
      residual coupling with a strength proportional to the fiber radiation loss is
      long range, decreasing as an inverse square root of the interfiber separation and
      exhibiting periodic variation. The possibility of building a directional coupler
      from touching Bragg fibers is discussed in view of the findings.

PMID- 15259720
TI  - Efficient method for the extraction of the conditional probability distribution
      of polarization mode dispersion.
AB  - A new method for obtaining the probability density function of polarization mode
      dispersion (PMD) conditioned on the measured PMD value at an offset optical
      frequency is introduced. This method is advantageous in its ability to accurately
      and efficiently estimate the conditional distribution far in the tails.

PMID- 15259721
TI  - Dependence of the brillouin frequency shift on strain and temperature in a
      photonic crystal fiber.
AB  - The dependence of the Brillouin frequency shift on strain in a photonic crystal
      fiber (PCF) was measured at a wavelength of 1320 nm for the first time to the
      authors' knowledge. Together with measurements of the dependence of the Brillouin
      frequency shift on temperature in the PCF, we demonstrate the feasibility of the
      highly precise simultaneous measurement of temperature and strain by use of the
      PCF in a distributed Brillouin sensing system with a spatial resolution of 15 cm.

PMID- 15259722
TI  - Confocal thermal-lens microscope.
AB  - The use of a confocal detection scheme in a dual-beam thermal-lens microscope is
      presented. The scheme allows the measurement of absorption factors down to 1.2 x
      10(-7) in a 0.35-microm3 volume by use of a heating laser power of 100 mW
      incident upon the sample. Results are presented that prove that a 450-nm axial
      resolution is possible when a 1.2 water immersion objective lens with a N.A. of
      1.2 is used.

PMID- 15259723
TI  - Spectral and temporal speckle field measurements of a random medium.
AB  - The zero-mean circular complex Gaussian field statistics of a random medium are
      experimentally demonstrated in the optical domain, thus verifying this key
      assumption of statistical optics. Using a frequency-tunable laser source in a
      fixed-path-length interferometer, we obtain optical field fluctuations in the
      time and frequency domains that clearly show that the ensemble-averaged temporal
      intensity converges to the photon transit time distribution, which for the
      samples used is in excellent agreement with a diffusion model.

PMID- 15259724
TI  - Control of spontaneous emission by complex nanostructures.
AB  - Spontaneous emission in the presence of complex nanostructures is discussed by
      use of a calculational scheme that permits us to deal with interfaces of
      arbitrary shape. Control over the field associated with the emission is shown to
      be attainable. In particular, decay rates are offered for geometries that lead to
      focusing and collimation of near- and far-field distributions. Emission from
      axially symmetric gratings is shown to lead to narrow angular distributions of
      emission, and focusing at the foci of dielectric ellipsoids is achieved for
      dimensions comparable with the wavelength. In the latter case the total emission
      rate for two atoms in an ellipsoidal cavity is shown to be enhanced in a way that
      deviates from the predictions of the Dicke effect by means of intermediate- and
      far-field contributions.

PMID- 15259725
TI  - Subhertz-linewidth Nd:YAG laser.
AB  - Light from a Nd:YAG laser at 1064 nm is independently stabilized to two Fabry
      Perot etalons situated on separate vibration-isolation platforms. A heterodyne
      beat measurement shows their relative frequency stability to be at the part-in
      10(15) level at 5 s and the relative linewidth to be less than 1 Hz.

PMID- 15259726
TI  - Tunable resonant optical microcavities by self-assembled templating.
AB  - Micrometer-scale optical cavities are produced by a combination of template
      sphere self-assembly and electrochemical growth. Transmission measurements of the
      tunable microcavities show sharp resonant modes with Q factors of >300 and 25
      fold local enhancement of light intensity. The presence of transverse optical
      modes confirms the lateral confinement of photons. Calculations show that
      submicrometer mode volumes are feasible. The small mode volumes of these
      microcavities promise to lead to a wide range of applications. in microlasers,
      atom optics, quantum information, biophotonics, and single-molecule detection.

PMID- 15259727
TI  - Single-frequency thulium-doped distributed-feedback fiber laser.
AB  - We have successfully demonstrated a single-frequency distributed-feedback (DFB)
      thulium-doped silica fiber laser emitting at a wavelength of 1735 nm. The laser
      cavity is less than 5 cm long and is formed by intracore UV-written Bragg
      gratings with a phase shift. The laser is pumped at 790 nm from a Ti:sapphire
      laser and has a threshold pump power of 59 mW. The laser has a maximum output
      power of 1 mW in a single-frequency, single-polarization radiation mode and is
      tunable over a few nanometers. To the best of the authors' knowledge, this is the
      first report of a single-frequency DFB fiber laser that uses thulium as the
      amplifying medium. The lasing wavelength is the longest demonstrated with DFB
      fiber lasers and yet is among the shortest obtained for thulium-doped silica
      fiber lasers.

PMID- 15259728
TI  - Improving the diffuse optical imaging spatial resolution of the cerebral
      hemodynamic response to brain activation in humans.
AB  - We compare two geometries of sources and detectors for optimizing the diffuse
      optical imaging resolution of brain activation in humans. Because of limitations
      in the instruments' dynamic range, most diffuse optical brain activation images
      have used only nonoverlapping measurements. We demonstrate theoretically and with
      a human experiment that a simple geometry of sources and detectors can provide
      overlapping measurements within the limitation of instrumentation dynamic range
      and produce an image resolution and localization accuracy that is twofold better.

PMID- 15259729
TI  - Quantitative phase-contrast imaging of cells with phase-sensitive optical
      coherence microscopy.
AB  - We describe a method for en face phase-contrast imaging of cells with a fiber
      based differential phase-contrast optical coherence microscopy system. Recorded
      en face images are quantitative phase-contrast maps of cells due to spatial
      variation of the refractive index and (or) thickness of various cellular
      components. Quantitative phase-contrast images of human epithelial cheek cells
      obtained with the fiber-based differential phase-contrast optical coherence
      microscopy system are presented.

PMID- 15259730
TI  - Do fluorescence decays remitted from tissues accurately reflect intrinsic
      fluorophore lifetimes?
AB  - Fluorescence spectroscopy and imaging methods, including fluorescence lifetime
      sensing, are being developed for noninvasive tissue diagnostics. The purpose of
      this study was to identify and quantify those factors affecting the accurate
      recovery of fluorophore lifetimes from inhomogeneous tissues in vivo. A Monte
      Carlo code was developed to numerically simulate time-resolved fluorescence
      measurements on layered epithelial tissues. Simulations were run with
      experimental parameters matching previously reported clinical studies in the
      gastrointestinal tract. The results demonstrate that variations in fluorescence
      decay time as large as those detected clinically between normal and premalignant
      tissues (approximately 2 ns) could be simulated by variations in tissue
      morphology or biochemistry, even when intrinsic fluorophore lifetimes were held
      constant.

PMID- 15259731
TI  - Four-wave mixing of light beams with engineered orbital angular momentum in cold
      cesium atoms.
AB  - We report an experimental demonstration that shows that the spatial structure
      carried by engineered coherent superpositions of light beams with orbital angular
      momentum can be mapped into the nonlinear polarization induced in a cloud of cold
      cesium atoms. The structure of such polarization was revealed by nearly
      degenerate four-wave-mixing processes.

PMID- 15259732
TI  - Periodically poled lithium niobate waveguide sum-frequency generator for
      efficient single-photon detection at communication wavelengths.
AB  - We present a device to facilitate single-photon detection at communication
      wavelengths based on continuous-wave sum-frequency generation with an
      upconversion efficiency exceeding 90%. Sum-frequency generation in a periodically
      poled lithium niobate waveguide is used to upconvert signal photons to the near
      infrared, where detection can be performed efficiently by use of silicon
      avalanche photodiodes.

PMID- 15259733
TI  - Self-channeling of subgigawatt femtosecond laser pulses in a ground-state
      waveguide induced in the hollow core of a photonic crystal fiber.
AB  - Femtosecond laser pulses with powers below the blowup threshold for self-focused
      beams are shown to experience spatial self-action in hollow-core photonic crystal
      fibers filled with argon, nitrogen, and atmospheric air. Regardless of the
      transverse field distribution at the input of the fiber, the output beam pattern
      in this regime tends to a circularly symmetric profile, corresponding to a ground
      state waveguide induced by laser pulses inside a hollow fiber.

PMID- 15259734
TI  - Polarization-insensitive cross correlation using two-photon absorption in a
      silicon photodiode.
AB  - We present experimental measurements of the polarization dependence of two-photon
      absorption in silicon photodiodes at 1550 nm, and we offer a simple theory that
      explains our observations. Based on this theory, we propose and demonstrate that
      it is possible to construct an optical cross-correlation system that is
      polarization insensitive, provided that one of the two input polarization states
      can be controlled.

PMID- 15259735
TI  - Optically active second-harmonic generation from a uniaxial fluid medium.
AB  - We have shown that optically active second-harmonic generation is allowed in a
      uniaxial fluid medium. A homeotropically aligned chiral smectic-A liquid crystal
      was used as an example. Phase matching was achievable by angle tuning. Chiral
      nonlinear susceptibility for the liquid crystal was deduced. The signal dropped
      precipitously as the sample underwent the transition from smectic-A to isotropic.

PMID- 15259736
TI  - Discrete propagation and spatial solitons in nematic liquid crystals.
AB  - We investigate, for the first time to our knowledge, the discrete propagation of
      near-infrared light in a voltage-controlled array of channel waveguides in
      undoped nematic liquid crystals under planar anchoring conditions. This novel
      geometry enables us to drive the system from one-dimensional bulk diffraction to
      discrete propagation and, for larger excitations, to discrete spatial solitons,
      or nematicons. The observed phenomena are adequately described by a scalar model
      that encompasses the voltage-dependent reorientational response of the material.

PMID- 15259737
TI  - Unification of radar phenomena as spacetime curvature: prediction and observation
      of an affine-phase effect.
AB  - The many properties of radar echoes and other radiative systems were recently
      described by Gabriel [J. Opt. Soc. Am. A 19, 946 (2002)] as lower-dimensional
      projections of simple forms in special relativity. A broader treatment including
      coherent phenomena is summarized, in which the phase properties of radar images
      and interferograms are also shown to have a simple unified structure. Their
      apparent complexity is a result of projection onto the lower dimension(s) of the
      observation. A predicted new property, locally scalable (affine) phase, is
      observed in a radar interferogram.

PMID- 15259738
TI  - Correlation matrix of a completely polarized, statistically stationary
      electromagnetic field.
AB  - It is shown that, for a 3 x 3 correlation matrix Wij(r, r, omega), (i, j = x, y,
      z) of the electric vector of a random, stationary electromagnetic field to
      represent a field that is completely polarized at a point r and frequency omega,
      each element of the matrix must factorize. More precisely, a necessary and
      sufficient condition for the correlation matrix to represent a fully polarized
      field at a point r is that the matrix has the form Wij(r, r, omega) =
      epsilon(i)*(r, omega)epsilon(j)(r, omega), where epsilon(i)(r, omega) (i = x, y,
      z) are deterministic functions, i.e., that all pairs of the Cartesian components
      of the electric field at a point r and frequency omega are completely correlated.

PMID- 15259739
TI  - Interferometric measurement of the degree of polarization and control of the
      contrast of intensity fluctuations.
AB  - We introduce a technique for determining the polarimetric characteristics of
      light by measuring the contrast of the intensity fluctuations in an
      interferometric setup. The method permits simultaneous measurement of the degree
      of polarization and of the second normalized Stokes component, which is related
      to the ellipsometric parameters azimuth and ellipticity, based on only two
      measurements. We also show that by using. phase modulation we can increase the
      signal-to-noise ratio as much as 40% under certain conditions.

PMID- 15259740
TI  - Time-domain mid-infrared frequency-comb spectrometer.
AB  - A novel type of Fourier-transform infrared spectrometer (FTIR) is demonstrated.
      It is based on two Ti:sapphire lasers emitting femtosecond pulse trains with
      slightly different repetition frequencies. Two mid-infrared beams-derived from
      those lasers by rectification in GaSe-are superimposed upon a detector to produce
      purely time-domain interferograms that encode the infrared spectrum. The
      advantages of this spectrometer compared with the common FTIR include ease of
      operation (no moving parts), speed of acquisition (100 micros demonstrated), and
      not-yet-shown collimated long-distance propagation, diffraction-limited
      microscopic probing, and electronically controllable chemometric factoring.
      Extending time-domain frequency-comb spectroscopy to lower (terahertz) or higher
      (visible, ultraviolet) frequencies should be feasible.

PMID- 15259741
TI  - Generation of femtosecond anti-stokes pulses through phase-matched parametric
      four-wave mixing in a photonic crystal fiber.
AB  - Phase-matched parametric four-wave mixing in higher-order guided modes of a
      photonic crystal fiber is shown to result in an efficient decay of 40-fs 800-nm
      Ti:sapphire laser pump pulses into an anti-Stokes signal with a central
      wavelength around 590-600 nm and a Stokes signal centered at 1.25 microm. The
      photonic crystal fiber is designed in such a way as to minimize the group
      velocity dispersion at the pump wavelength, phase match the parametric four-wave
      mixing process, and reduce the group delay between the pump and the anti-Stokes
      pulses. The duration of the anti-Stokes pulse under these conditions, as shown by
      cross-correlation frequency-resolved optical gating measurements, is less than
      200 fs.

PMID- 15259742
TI  - Oscillation of the refractive index at the focal region of a femtosecond laser
      pulse inside a glass.
AB  - The temporal evolution of refractive-index change produced by a tightly focused
      femtosecond (fs) laser pulse inside a soda-lime glass plate was investigated by
      use of a transient lens method with subpicosecond time resolution. An oscillating
      behavior of the light intensity in the central region of the probe beam was
      observed 0-1500 ps after irradiation of the plate. The oscillation was
      interpreted in terms of a rapid temperature increase and the ensuing propagation
      of the pressure wave. This study is to our knowledge the first real-time
      observation of refractive-index change inside a glass induced by a fs laser
      pulse.

PMID- 15259743
TI  - Femtosecond direct space-to-time pulse shaping in an integrated-optic
      configuration.
AB  - We demonstrate femtosecond operation of an integrated-optic direct space-to-time
      pulse shaper for which there is a direct mapping (no Fourier transform) between
      the spatial position of the masking function and the temporal position in the
      output waveform. The apparatus is used to generate trains of more than 30 pulses
      as an ultrafast optical data packet over approximately an 80-ps temporal window.

PMID- 15259744
TI  - Precise frequency transfer through a fiber network by use of 1.5-microm mode
      locked sources.
AB  - We report the precise transfer of radio-frequency signals by use of the pulse
      repetition frequency of mode-locked laser sources at 1.5 microm transmitting
      through a fiber network. The passive transfer instability through a 6.9-km fiber
      is below 3 x 10(-14) at 1 s, which is comparable with the optical carrier
      frequency transfer of a narrow-linewidth cw laser. The instability of the
      measurement system is below 7 x 10(-15) at 1 s. It is noted that the pulsed mode
      of operation offers almost an order-of-magnitude improvement in stability at 1 s
      over that with a sinusoidal amplitude modulation on an optical carrier.

PMID- 15259745
TI  - Measurement of the carrier-envelope phase of few-cycle laser pulses by use of
      asymmetric photoionization.
AB  - Using numerical solutions of the time-dependent Schrodinger equation for a
      hydrogen and a helium atom in a linearly polarized, few-cycle laser field, we
      calculate the photoelectron left-right asymmetry measured by two opposing
      detectors placed along the laser polarization vector, with the laser focus in the
      center. We find a simple dependence of this asymmetry on carrier-envelope (CE)
      phase phi for laser intensities slightly below the tunneling regime, which may
      allow us to measure (or to calibrate) and to stabilize the CE phase. In
      particular, we suggest that the condition of zero asymmetry for few-cycle pulses
      may be useful for both these goals.

PMID- 15259746
TI  - Alosetron use drops dramatically with risk management.

PMID- 15259747
TI  - Effective leadership is vital to pharmacy's future.

PMID- 15259748
TI  - Rural, small hospitals face JCAHO challenges.

PMID- 15259749
TI  - New immunosuppressant class not without serious concerns.

PMID- 15259750
TI  - Caremark's gain is Medco's loss.

PMID- 15259751
TI  - Electronic adverse-drug-reaction-reporting program.

PMID- 15259752
TI  - West Nile virus infection.
AB  - PURPOSE: The epidemiology, virology, and transmission of West Nile virus (WNV)
      are reviewed, and the clinical features, diagnosis, and treatment of WNV
      infection are examined. SUMMARY: WNV infection is caused by a flavivirus
      transmitted from birds to humans through the bite of culicine mosquitoes. WNV was
      discovered in the blood of a febrile woman from Uganda's West Nile province in
      1937. The first case of domestically acquired WNV infection was reported in the
      United States in 1999 in New York. Since then, WNV infection has spread rapidly
      across the United States, with 9306 confirmed cases and 210 deaths reported from
      45 states in 2003. It is still not clear how WNV was introduced into North
      America. WNV is a small, single-stranded RNA virus and a member of the Japanese
      encephalitis virus antigenic complex. While most humans infected with WNV are
      asymptomatic, some may develop an influenza-like illness. Disease surveillance
      remains the cornerstone for the early recognition and control of WNV. We describe
      one case of WNV infection with an update on the disease. Strategies for the
      prevention and control of this infection are reviewed. CONCLUSION: There is no
      established treatment for WNV infection. Currently, prevention and control are
      the only measures that help decrease the morbidity and mortality associated with
      WNV infection. As the number of cases escalates and the geographic distribution
      of WNV infection widens, the epidemic will continue to pose a major challenge to
      clinicians in the coming years. There is an urgent need for more research on the
      pathogenesis and treatment of WNV infection.

PMID- 15259753
TI  - Enfuvirtide: first fusion inhibitor for treatment of HIV infection.
AB  - PURPOSE: The mechanism of action, pharmacokinetics, clinical efficacy, adverse
      effects, and availability of enfuvirtide are discussed. SUMMARY: To date, 20
      antiretrovirals have been approved by FDA for the treatment of HIV infection. The
      recent approval of enfuvirtide offers a new and fourth class of antiretroviral
      agents called fusion inhibitors. Enfuvirtide is indicated for use in treatment
      experienced patients who have evidence of viral replication despite receiving
      current therapy. The drug is a 36-amino-acid synthetic peptide that prevents
      completion of the HIV fusion sequence. Absolute bioavailability after
      subcutaneous injection is 84%. Clinical trials indicate that adding enfuvirtide
      to a salvage regimen in heavily treated patients may lead to an improved
      virologic response. Up to a 1.48 log decrease in the viral load was seen at 48
      weeks when enfuvirtide was combined with an optimized background regimen.
      Patients who have at least two or more active drugs in the regimen, a CD4+ cell
      count of >100 cells/mm3, and previous exposure to two or more antiretrovirals
      prior to starting enfuvirtide appear to respond best. The most common adverse
      effect, occurring in 98% of all enfuvirtide recipients, is an injection-site
      reaction that generally can be managed nonpharmacologically. A much less common
      but more significant concern is an increased risk of bacterial pneumonia.
      Enfuvirtide is available through the Fuzeon Progressive Distribution Program. The
      annual cost of therapy is about 24,000 dollars. CONCLUSION: Enfuvirtide is the
      first fusion inhibitor available for the treatment of HIV infection. The drug is
      indicated for use with other antiretroviral agents in treatment-experienced
      patients who have evidence of HIV replication despite ongoing antiretroviral
      treatment.

PMID- 15259754
TI  - Prescription-filling rates for key medications in Veterans Affairs patients after
      coronary artery bypass grafting.
AB  - PURPOSE: The six-month prescription-filling rates for key secondary-prevention
      drugs in Department of Veterans Affairs (VA) patients who had undergone coronary
      artery bypass grafting (CABG) were studied. METHODS: Patient records for elective
      CABG from April 2000 through March 2002 (divided into four six-month periods)
      were analyzed. The study population included 8925 CABG-only patients surviving to
      hospital discharge. For each six-month period and in aggregate, the primary study
      endpoint was the six-month prescription-filling rate. RESULTS: Across the four
      six-month periods, prescription-filling rates increased for all categories of
      medications studied. There were modest progressive increases for lipid-lowering
      agents, statins, -blockers, angiotensin-converting-enzyme Inhibitors, and
      angiotensin-receptor blockers. The antithrombotic-filling rate averaged 88.5%.
      Filling rates for aspirin were much higher than for aspirin alternatives.
      CONCLUSION: Prescription-filling rates for post-CABG medications in VA facilities
      were generally high and suggested compliance with guidelines for the prevention
      of cardiovascular events.

PMID- 15259755
TI  - Trends in child and teen nonprescription drug abuse reported to a regional poison
      control center.
AB  - PURPOSE: Trends in child and teen nonprescription drug abuse reported to a
      regional poison control center over a 10-year period were examined. METHODS:
      Human exposures to toxic substances reported to the Utah Poison Control Center
      between January 1990 and December 1999 were reviewed. Cases were selected for
      analysis if the exposure involved a nonprescription drug, the patient was 6-19
      years old, and the reason for exposure was intentional abuse. Frequencies and
      cross-tabulations were calculated to identify trends in nonprescription drug
      abuse. RESULTS: There were 2214 reports of intentional drug abuse among children
      and teenagers 6-19 years old. Of those, 844 (38.1%) involved nonprescription
      drugs. The percentage of exposures Involving nonprescription products varied
      every year and declined over time. Exposures were slightly more common In males
      (51.7%). The site of exposure was a residence in 65% of cases and a school in 10%
      of cases. The majority of patients with exposures (68.4%) were treated In a
      health care facility. The most common types of nonprescription medications abused
      were drugs with anticholinergic properties, caffeine, dextromethorphan, and
      nonprescription stimulants. CONCLUSION: Reports of the Intentional abuse of
      nonprescription drugs by children and teenagers were common at a regional poison
      control center. There was significant variation in the type of nonprescription
      medication most commonly abused. The knowledge of these trends may assist public
      health policymakers, physicians, pharmacists, and child educators in their
      attempts to curb nonprescription drug abuse. drugs.

PMID- 15259756
TI  - Effect of warfarin nonadherence on control of the International Normalized Ratio.
AB  - OBJECTIVE: The frequency and causes of ab- errant International Normalized Ratios
      (INRs) in warfarin recipients and the percentage explainable by warfarin
      nonadherence were studied. METHODS: The medical records of patients whose
      warfarin therapy was monitored by a telephone-based anticoagulation service in a
      Midwestern urban hospital between March 2000 and March 2001 were reviewed for
      causes of out-of-range INRs, the percentage of out-of-range INRs attributable to
      warfarin nonadherence, and demographic and clinical variables predictive of
      nonadherence. RESULTS: Data from 347 patients were studied. The cohort yielded
      4305 INRs, of which 1002 (23%) were out of range (lower than 1.8 or higher than
      3.4). Thirty-six percent of the out-of-range INRs were due to warfarin or dietary
      nonadherence, 9% were due to medical systems problems (including drug
      interactions), 18% were due to a change in clinical status, and 38% were
      idiopathic. Age younger than 65 years, age greater than 80 years, and living
      closer to the laboratory were predictive of warfarin nonadherence. CONCLUSION:
      Warfarin nonadherence was the most common cause of explainable aberrant INRs in
      patients taking warfarin. Age younger than 65 years, age greater than 80 years,
      and living close to the laboratory were predictive of warfarin nonadherence.

PMID- 15259757
TI  - Clinical and economic benefits of a meropenem dosage strategy based on
      pharmacodynamic concepts.
AB  - PURPOSE: The clinical and economic outcomes of a meropenem dosage strategy based
      on pharmacodynamic concepts are retrospectively reviewed. METHODS: The medical
      records of all patients receiving at least one day of meropenem at a large
      teaching hospital during 2002 were reviewed. Patients were included if they were
      clinically evaluable, had no prior successful antibiotic therapy, and received a
      meropenem dosage appropriate for renal function. Clinical outcomes were evaluated
      by the rate of response (days to normalization of temperature or lymphocyte
      count) and success rate. A cost-minimization analysis was performed from the
      hospital's perspective for level 1, 2, and 3 costs. The average wholesale price
      of meropenem for 2002 and the cost for one hospital day at our institution were
      used to calculate economic outcomes. RESULTS: Of the 136 patients identified as
      receiving at least one dose of meropenem, 85 met inclusion criteria, of whom 45
      received meropenem 500 mg every six hours and 40 received meropenem 1000 mg every
      eight hours. No significant differences in demographics, site of infection,
      meropenem-related length of stay, or rate of response were found. Clinical
      success rates were similar between groups (p = 0.862). Patients taking the 500-mg
      regimen received less meropenem during treatment than those in the 1000-mg group
      (13 g versus 18 g, respectively) (p = 0.012). Median level 1 and 2 costs were
      significantly lower for the 500-mg regimen (p = 0.009 and p = 0.008,
      respectively). Level 3 costs were not significantly different. CONCLUSION: A
      pharmacodynamically designed meropenem dosage strategy of 500 mg every six hours
      yielded similar clinical outcomes to a regimen of 1000 mg every eight hours and
      reduced the daily drug acquisition costs associated with antibiotic therapy.

PMID- 15259758
TI  - Pharmacist-managed service providing penicillin allergy skin tests.
AB  - PURPOSE: A penicillin allergy skin-testing service run by pharmacists is
      described. SUMMARY: A board-certified allergist trained pharmacists at a tertiary
      care teaching hospital to administer penicillin allergy skin tests and interpret
      the results. A major objective of the service was to avoid unnecessary use of
      vancomycin and quinolones in patients claiming but not actually having a
      penicillin allergy. Patients with a severe type I reaction to penicillin during
      the preceding five years, patients with a confirmed history of a type II-IV
      reaction to penicillin, and severely immunosuppressed patients were not eligible
      for testing. As of July 2003, 26 patients had been enrolled in the service. A
      type I penicillin reaction was ruled out by the drug allergy history for 3
      patients. The results were negative in 22 of the 23 patients who received skin
      testing, and in 1 the result was indeterminate. A penicillin or a beta-lactam
      antibiotic was administered to all 26 patients. No patient had a significant
      adverse reaction to skin testing or drug administration. CONCLUSION: A pharmacist
      managed penicillin allergy skin-testing service was well received by physicians
      and showed potential to avoid unnecessary use of alternative antibiotics.

PMID- 15259759
TI  - Fat-globule size in a propofol emulsion containing sodium metabisulfite.
AB  - PURPOSE: The size distribution of fat globules from previously unopened,
      unexpired vials of Gensia Sicor's 1% propofol injectable lipid emulsion was
      studied. METHODS: Fat globules in 20-mL samples from 50- and 100-mL vials of
      Gensia Sicor's 1% propofol emulsion containing 0.025% sodium metabisulfite were
      measured and counted by a laser-based, single-particle optical sensing technique.
      Measurements were performed during May 2001, June 2002, and October 2002,
      corresponding, respectively, to 17-21, 5-9, and 1-5 months before the vials'
      expiration dates, depending on the lot. Between measurements, the vials were
      stored at 4-22 degrees C. It was assumed that the pH for all lots was 4.5-6.4.
      Two separate lots of the innovator propofol emulsion (AstraZeneca) containing
      EDTA and having a labeled pH of 7.0-8.5 were analyzed in October 2002 in a post
      hoc assessment as the vials neared their expiration date. RESULTS: In May 2001,
      the volume-weighted percentage of fat globules with a diameter of >5 microm
      (PFAT5) was <0.05% for all seven Gensia Sicor lots. In four of the lots, PFAT5
      increased significantly between May 2001 and June 2002. In all seven lots, PFAT5
      increased significantly between May 2001 and October 2002. The two lots of the
      AstraZeneca product, tested two or three months before expiration, had low PFAT5
      values. CONCLUSION: In samples from unopened, unexpired, and properly stored
      vials of Gensia Sicor propofol formulated at pH 4.5-6.4, PFAT5 increased over 18
      months and in most cases exceeded 0.05% by the end of the study.

PMID- 15259760
TI  - Estimating the volume of prefilled bags of 5% dextrose injection.

PMID- 15259761
TI  - Pharmacist interventions in electronic drug orders entered by prescribers.

PMID- 15259762
TI  - Carvedilol and metoprolol European trial: do the results merit challenge?

PMID- 15259763
TI  - Sequence similarities of protein kinase substrates and inhibitors with
      immunoglobulins and model immunoglobulin homologue: cell adhesion molecule from
      the living fossil sponge Geodia cydonium. Mapping of coherent database
      similarities and implications for evolution of CDR1 and hypermutation.
AB  - Sequences of immunoglobulin (Ig) domains of adhesive molecule GSAMS from the
      living fossil sponge Geodia cydonium were compared with the important motif of
      peptide protein kinase substrates and inhibitors (PKSI), detail PKSI sequences,
      and a common template sequence, derived from structures determined previously. We
      found the site-restricted sequence similarities to these peptide sequences
      predominantly in the GSAM Ig1 domain of GSAMS in the domain region related to
      corresponding Ig similarities detected earlier. Additional sequence block-related
      analysis revealed the presence of CDR1-like segments within PKSI-related regions
      and resulted in the detection of increased numbers of hypermutation motifs just
      in the CDR1-like segment of GSAM Ig1 (GSAM(cdrl.1)). In the following database
      searches with PKSI-related regions and GSAM(cdr1.1) we looked for: (i) peptide
      similarities present in the context of Ig domains or related structures in a
      large range of species from Archaea to Vertebrata, and (ii) some special
      nucleotide similarities.

PMID- 15259764
TI  - Evolutionary relatedness between glycolytic enzymes most frequently occurring in
      genomes.
AB  - More than 100 sequenced genomes were searched for genes coding for the enzymes
      involved in glycolysis in an effort to find the most frequently occurring ones.
      Triosephosphate isomerase (TIM), glyceraldehyde-3-phosphate dehydrogenase (GAPD),
      phosphoglycerate kinase (PGK) and enolase (ENOL) were found to be present in 90
      investigated genomes all together. The final set consisted of 80 prokaryotic and
      10 eukaryotic genomes. Of the 80 prokaryotic genomes, 73 were from Bacteria, 7
      from Archaea. Two microbial genomes were also from Eucarya (yeasts). Eight
      genomes of nonmicrobial origin were included for comparison. The amino acid
      sequences of TIMs, GAPDs, PGKs and ENOLs were collected and aligned, and their
      individual as well as concatenated evolutionary trees were constructed and
      discussed. The trees clearly demonstrate a closer relatedness between Eucarya and
      Archaea (especially the concatenated tree) but they do not support the hypothesis
      that eukaryotic glycolytic enzymes should be closely related to their alpha
      proteobacterial counterparts. Phylogenetic analyses further reveal that although
      the taxonomic groups (e.g., alpha-proteobacteria, gamma-proteobacteria,
      firmicutes, actinobacteria, etc.) form their more or less compact clusters in the
      trees, the inter-clade relationships between the trees are not conserved at all.
      On the other hand, several examples of conservative relatedness separating some
      clades of the same taxonomic groups were observed, e.g., Buchnera along with
      Wigglesworthia and the rest of gamma-proteobacteria, or mycoplasmas and the rest
      of firmicutes. The results support the view that these glycolytic enzymes may
      have their own evolutionary history.

PMID- 15259765
TI  - Disruption of the RAD51 gene sensitizes S. cerevisiae cells to the toxic and
      mutagenic effects of hydrogen peroxide.
AB  - The RAD51 gene was disrupted in three different parental wild-type strains to
      yield three rad51 null strains with different genetic background. The rad51
      mutation sensitizes yeast cells to the toxic and mutagenic effects of H2O2,
      suggesting that Rad51-mediated repair, similarly to that of RecA-mediated, is
      relevant to the repair of oxidative damage in S. cerevisiae. Moreover, pulsed
      field gel electrophoresis analysis demonstrated that increased sensitivity of the
      rad51 mutant to H2O2 is accompanied by its decreased ability to repair double
      strand breaks induced by this agent. Our results show that ScRad51 protects yeast
      cells from H2O2-induced DNA double-strand breakage.

PMID- 15259766
TI  - A new group of potential antituberculotics: hydrochlorides of piperidinylalkyl
      esters of alkoxy-substituted phenylcarbamic acids.
AB  - A group of 31 of alkoxy-substituted phenylcarbamic acids with the alkoxy group in
      ortho, meta or para position, and methyl or ethoxymethyl attached to the ethylene
      moiety in position 1, including both basic ethyl esters and derivatives branched
      on ethylene, were evaluated for in vitro antimycobacterial activity against
      Mycobacterium tuberculosis, M. kansasii, and M. avium. To describe the structure
      antimycobacterial activity relationships (QSARs), an approach based on a
      combination of the Free-Wilson analysis was used to express the influence of the
      substituents on the ethylene group as well as the position of the alkoxy groups
      on the phenyl ring and of the hydrophobicity of alkyls. In vitro
      antimycobacterial activity becomes higher with increasing hydrophobic properties
      of the alkoxy groups. The para- and meta-substituted derivatives were more active
      than the ortho-substituted ones. Substitution of ethylene in position 1 by methyl
      increased the activity against M. tuberculosis, a similar substitution by
      ethoxymethyl increased the activity against M. kansasii. The most active
      compounds were piperidinyl-1-(ethoxymethyl)ethylesters of heptoxyphenylcarbamic
      acids.

PMID- 15259767
TI  - Bacterial diversity in Malan ice core from the Tibetan Plateau.
AB  - Three ice core samples were collected from the Malan ice core drilled from the
      Tibetan Plateau, and three 16S rDNA clone libraries by direct amplification from
      the ice-melted water were established. Ninety-four clones containing bacterial
      16S rDNA inserts were selected. According to restriction fragment-length
      polymorphism analysis, 11 clones were unique in the library from which they were
      obtained and used for partial sequence and phylogenetic analysis, and compared
      with 8 reported sequences from the same ice core at depth 70 m. Differences among
      the samples were apparent in clone libraries. The phylotypes were dominated by
      the Proteobacteria group, Acinetobacter sp. and Cytophaga-Flavobacterium
      Bacteroides (CFB) group. They accounted for 92.5% (Proteobacteria), 100%
      (Acinetobacter sp.), 34.4% (CFB) and 100% (beta-Proteobacteria) in the clone
      libraries from the samples at ice depths 35, 64, 70, and 82 m, respectively. The
      Acinetobacter sp. was only found in the deposition at ice depth 82 m and closely
      clustered with gamma-Proteobateria. Two members (Malan A-21 and 101) of alpha
      Proteobacteria from the sample of 35 m and two (Malan B-26 and 48) of beta
      Proteobacteria of 64 m were loosely clustered (< 95% similarity) with known
      bacteria, represented new genera in ice bacteria.

PMID- 15259769
TI  - Hydroxylation of progesterone by some Trichoderma species.
AB  - Thirty-three isolates belonging to six species of the genus Trichoderma were
      tested for the ability to hydroxylate progesterone to 11alpha-, 11beta-,
      11alpha,17alpha- and 6beta, 17alpha-derivatives, and epicortisol. T. aureoviride,
      T. harzianum, T. polysporum and T. pseudokoningii produced 11alpha
      hydroxyprogesterone. T. harzianum and T. hamatum can form only the 11beta-isomer.
      T. koningii and T. hamatum produced 11alpha-, 11beta-, 11alpha,17alpha- and
      6beta,11alpha-hydroxy derivatives. 11alpha, 11beta, 6beta,11alpha- and
      11alpha,17alpha-hydroxyprogesterones and epicortisol are produced by T.
      aureoviride and T. pseudokoningii. Cortisol was produced only when the medium was
      fortified by 10 g/L peptone. This is the first record of conversion of
      progesterone to mono-, di- and trihydroxyprogesterones by these Trichoderma
      species.

PMID- 15259768
TI  - Physiological and morphological changes in autolyzing Aspergillus nidulans
      cultures.
AB  - Physiological and morphological changes in carbon-limited autolyzing cultures of
      Aspergillus nidulans were described. The carbon starvation arrested conidiation
      while the formation of filamentous and "yeast-like" hyphal fragments with
      profoundly altered metabolism enabled the fungus to survive the nutritional
      stress. The morphological and physiological stress responses, which maintained
      the cellular integrity of surviving hyphal fragments at the expense of autolyzing
      cells, were highly concerted and regulated. Moreover, sublethal concentrations of
      the protein synthesis inhibitor cycloheximide or the mitochondrial uncoupler 2,4
      dinitrophenol completely blocked the autolysis. In accordance with the
      propositions of the free-radical theory of ageing reactive oxygen species
      accumulated in the surviving fragments with a concomitant increase in the
      specific superoxide dismutase activity and a continuous decrease in cell
      viability. Glutathione was degraded extensively in carbon-starving cells due to
      the action of gamma-glutamyltranspeptidase, which resulted in a glutathione
      glutathione disulfide redox imbalance during autolysis.

PMID- 15259770
TI  - Physiology of Anabaena khannae and Chlorococcum humicola under fluoride stress.
AB  - Sodium fluoride showed pH-dependent physiological responses in the two test
      microalgae Anabaena khannae and Chlorococcum humicola. A. khannae showed severe
      membrane damage with fluoride at low pH with leakage of pigments and
      electrolytes. Annihilation of photosynthesis along with inhibition in 14C uptake
      was observed at pH 6 with 50 mg/L fluoride. While respiration was less affected
      in the cyanobacterium, C. humicola showed 30 % inhibition in respiratory
      activity. Resistance of C. humicola to fluoride toxicity has been attributed to
      the hindrance provided by the thick cell envelope, intracellular compartmentation
      and increase in extracellular pH as a consequence of its metabolism.

PMID- 15259771
TI  - Combined infection of Ixodes ricinus with three Borrelia burgdorferi sensu lato
      genotypes.
AB  - Ixodes ricinus ticks were collected by random collections from western and
      central Slovakia during the years 1996-98. The midgut content of 240 ticks was
      examined by dark-field microscopy and submitted for cultivation for the presence
      of borrelias. Spirochetes were found in 21 unfed and host-seeking adults and
      nymphs (8.8%). By the analysis of restriction fragment length polymorphism (RFLP)
      one sample from unfed I. ricinus male from western Slovakia was identified as a
      triple infection of Borrelia burgdorferi sensu stricto, B. garinii and B.
      afzelii. The simultaneous presence of different B. burgdorferi genospecies in one
      midgut sample (triple infection in the tick) could be observed only after the
      multipart amplification of denaturated DNA and subsequent pooling of the products
      for further analysis.

PMID- 15259772
TI  - Synergic activity of selenium and probiotic bacterium Enterococcus faecium M-74
      against selected mutagens in Salmonella assay.
AB  - Concentrated extracts of MRS (De Man-Rogosa-Sharpe) media in which probiotic
      bacterium Enterococcus faecium strain M-74 was grown exerted different
      antimutagenic activity against ofloxacin-, N-methyl, N'-nitro-N-nitrosoguanidine-
      and sodium 5-nitro-2-furylacrylate-induced mutagenicity in Salmonella typhimurium
      assay depending on the presence (+Se) or absence of disodium selenite
      pentahydrate (-Se). The antimutagenicity of MRS(+Se) extract was higher than that
      of MRS(-Se) extract. Selenium enhanced also the antimutagenic effect of both live
      and killed cells of E. faecium M-74, respectively. The live bacteria decreased
      the mutagenicity of selected substances more than killed cells. Synergic activity
      of selenium with the bacterium was also manifested.

PMID- 15259773
TI  - Characterization of a complex restriction-modification system detected in
      Staphylococcus aureus and Streptococcus agalactiae strains isolated from
      infections of domestic animals.
AB  - Characterization of classic type II restriction-modification systems (RMS)
      (restriction endonucleases and modification methyltransferases) was carried out
      in isolates of Staphylococcus aureus and Streptococcus agalactiae obtained from
      clinical material. Among the 100 isolates of S. aureus two different RMS type II
      were detected. The first was expressed in isolates 32 and 33 (Sau32 I and Sau33
      I); the targeting sequence was determined as 5'-GGN CC-3' (Sau96 I isoschizomer).
      The second was found in isolates no. 90, 93, 96*, and 98 (Sau90 I, Sau93 I,
      Sau96* I, Sau98 I) and enzymes recognized sequence 5'-CTY RAG-3' (SmlI
      isoschizomer). Analysis of 40 isolates of S. agalactiae revealed only one RMS; it
      was detected in two isolates (no. 16 and 23; Sag16 I and Sag23 I). Restriction
      endonuclease expressed by these isolates cleaved DNA in sequence 5'-CTG CA/G-3'
      (PstI isoschizomer). In RMS-positive S. aureus and S. agalactiae isolates plasmid
      DNA capable of replication in Escherichia coli and Bacillus subtilis was also
      detected and isolated.

PMID- 15259774
TI  - Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a
      part of defense mechanisms.
AB  - To investigate whether hemocytes of Bombyx mori (Lepidoptera) larvae produce
      reactive oxygen species (ROS) as part of the oxidative killing of invading
      pathogens, the production of ROS was measured as a luminol- and lucigenin
      enhanced chemiluminescence of unstimulated or stimulated (zymosan particles,
      phorbol myristate acetate, calcium ionophore, rice starch or Xenorhabdus
      nematophila) hemolymph. No detectable ROS production was found. The spontaneous
      and activated ROS production measured with hemocytes, i.e. under the conditions
      when the antioxidative potential of hemolymph plasma was eliminated, was again
      undetectable. Likewise, ROS production by isolated hemocytes was observed by
      spectrophotometric (NBT test, cytochrome c assay) and fluorimetric (using
      dihydrorhodamine and hydroethidine probes) methods. Hence none of the
      experimental approaches used indicated the production of ROS by hemocytes of B.
      mori larvae as part of their immune response.

PMID- 15259775
TI  - Proteolytic activity in Serratia marcescens clinical isolates.
AB  - Exoproteinase production was demonstrated in 64 clinical isolates of S.
      marcescens. A significant relationship was found between the site of origin
      (autopsy material, hemocultures, various other sources), proteinase activity, and
      LD50 of the analyzed isolates. The number of exoproteinases varied during a 14-h
      incubation in batch cultures; the most frequently found was a 57.5-kDa proteinase
      which was observed in all analyzed strains. The exoproteinase production was
      shown to be related to strain virulence.

PMID- 15259777
TI  - What are production diseases, and how do we manage them?
AB  - The term "Production Diseases" referred traditionally to those diseases induced
      by management practices, metabolic diseases are typical examples. Recently, the
      term "Production related diseases" has been enhanced to include other traits,
      such as infertility, and diseases such as mastitis and lameness that might
      involve infectious agents but exacerbated by nutritional or managemental factors.
      The presentation deals with Production Diseases in the context of integrated herd
      health programs, using periparturient diseases and traits as an example. Studies,
      based on 9377 lactations of cows calving in the period 1995 through 1998 from the
      author's practice in 7 Israeli Holstein herds, show that most periparturient
      diseases and traits are followed by increased culling, lower production
      associated with late peaks and lower persistency, and impaired fertility. The
      effects are independent of other diseases, and at times are long lasting.
      Production Diseases are often multifactorial and appear at the same stage of
      lactation. Independent relationships among them must be established, so that
      common cause effects, direct and indirect causal associations, and incidental
      relationships can be differentiated. Control of Production Diseases often
      involves various disciplines and therefore calls for a "multivariate approach".
      Such an approach, centered on the herd, has led to the adaptation of integrated
      programs for herd health. The programs are characterized by the adaptation of
      multidisciplinary, multifactorial, and a population approach to clinical
      entities. Preventive measures and routine examinations are the hard core of
      programs, but deeper involvement in nutrition, production and economics is called
      for. A routine monitoring and causal analysis of periparturient traits and
      diseases, production, fertility and abortions are carried out, relevant data are
      processed, and monitoring reports are issued routinely. Five different linear
      regression models evaluate factors responsible for losses of a) peak milk yield;
      b) economy corrected (ECM) peak milk yield; c) extended 305-d milk yield; d)
      daily 3.5% FCM in the first 90 days in milk; and e) persistencies. Three
      different logistic and linear regression models evaluate factors that contribute
      to a) "non pregnancy to first service"; b) unobserved heat; and c) open days.
      Narrowing down the field of investigation is essential for an intervention to be
      efficient. Conclusions are drawn from the epidemiological study and the proposed
      recommendations are weighed with cost/benefit considerations. Possible losses are
      quantified and used with expected return value in decision analysis. Production
      Diseases are at times the outcome of managemental mistakes brought about by the
      drive for higher yields. Integrated herd health programs help to control the
      negative effects of management by enhancing production under optimal feeding and
      management regimens. The estimated contribution of improved management to the
      Israeli national herd phenotypic increase in yield, and the improved fertility
      that followed the increase in milk yield presented, show that the goal is within
      reach.

PMID- 15259778
TI  - Bovine spongiform encephalopathy (BSE)--infectious, contagious, zoonotic or
      production disease?
AB  - In 1986, a new progressive neurological condition similar to scrapie of sheep and
      goats was recognised in cattle in the United Kingdom (UK), and was named bovine
      spongiform encephalopathy (BSE). There is an ongoing discussion whether BSE
      should be classified as infectious, contagious, or zoonotic, and if it fits the
      definition of a production disease. The objective of this work is to briefly
      describe the main characteristics of transmissible spongiform encephalopathies
      (TSE), to review the epidemiology of BSE, and to address the question of how to
      classify BSE. TSEs are characterised as chronic wasting diseases with spongiform
      vacuolation and the accumulation of infectious prion protein (PrP(Sc)) in the
      central nervous system. TSE infectivity is very difficult to inactivate. Cattle
      BSE most likely originated from sheep scrapie, although this will remain to be an
      issue for debate. The disease can be transmitted from cattle to a range of
      species, and has resulted in smaller TSE epidemics in domestic cats, zoo cats and
      zoo ruminants, and in humans. Transmission in the field occurred through feed
      containing ruminant-derived protein, and measures to prevent the recycling of
      infectivity have proven effective to reduce the number of new infections.
      Mandatory reporting of clinical suspects combined with targeted screening of risk
      populations is needed to assess the BSE status of a country. Infection studies
      and the transmissibility to other species classify BSE as infectious and
      zoonotic. Absence of excretion of the agent, and therefore of horizontal
      transmission, categorise BSE as non-contagious. However, BSE is a multifactorial
      infectious disease that is dependent on management factors (mainly feeding), and
      therefore fits into the broader definition of production diseases.

PMID- 15259776
TI  - Tick saliva in anti-tick immunity and pathogen transmission.
AB  - When feeding on vertebrate host ticks (ectoparasitic arthropods and potential
      vectors of bacterial, rickettsial, protozoal, and viral diseases) induce both
      innate and specific acquired host-immune reactions as part of anti-tick defenses.
      In a resistant host immune defense can lead to reduced tick viability, sometimes
      resulting in tick death. Tick responds to the host immune attack by secreting
      saliva containing pharmacologically active molecules and modulating host immune
      response. Tick saliva-effected immunomodulation at the attachment site
      facilitates both tick feeding and enhances the success of transmission of
      pathogens from tick into the host. On the other hand, host immunization with
      antigens from tick saliva can induce anti-tick resistance and is seen to be able
      to induce immunity against pathogens transmitted by ticks. Many pharmacological
      properties of saliva described in ticks are shared widely among other blood
      feeding arthropods.

PMID- 15259779
TI  - Research School for Animal Production and Health (RAPH)--a description of a
      Danish research education initiative.

PMID- 15259780
TI  - Ethical perspectives on production diseases in farm animals.

PMID- 15259781
TI  - Co-ordinated interdisciplinary efforts on research in animal production and
      health.
AB  - The objectives are to review results and experiences from interdisciplinary
      research projects in Research Centre for the Management of Animal Production and
      Health (CEPROS) concerning scientific content, organisation, and collaboration.
      The Centre has been founded as a result of an agreement between four
      institutions: the Danish Institute of Agricultural Sciences (DIAS), the Danish
      Veterinary Laboratory (DVL), the Danish Veterinary Institute for Virus Research
      (DVIV) and The Royal Veterinary and Agricultural University (KVL). CEPROS is a
      "research centre without walls" and is physically located as an integrated part
      of the four institutions named above. The Centre has close collaboration with the
      industry. The superior goals of the Centre are to co-ordinate fundamental and
      applied research and simultaneously integrate the veterinary and the production
      oriented livestock research within animal health and welfare, taking into
      consideration the production economics and reduced use of medication. The
      assignment of the Centre is to initiate and carry out research, aiming to
      investigate the influence of breeding and production systems on animal health and
      welfare as well as on production and product quality. The Centre has since 1997
      established 16 interdisciplinary research projects dealing with cattle, pigs,
      poultry, or mink. The scientific content can be divided into three research
      clusters: A. Management of animal production and health in production systems, B:
      Pathogenesis of production diseases, and C. Animal health economics. In Cluster
      A, the physical environments of production systems have been investigated,
      broader definitions of the concept health have been established and used in
      identification of risk factors. Cluster B has investigated physiological,
      immunological and genetic mechanisms behind development of production diseases
      and how to apply this knowledge in disease prevention. The cluster in animal
      health economics has developed decision support tools for disease control in
      swine and cattle herds. The interdisciplinary research groups organised in a
      centre without walls are found very useful for dealing with complex issues. The
      initial phases in the projects may be long as it takes time for different
      researchers to define common goals and identify methods. The individual
      researcher must get some insight in other disciplines without loosing his/her own
      area of expertise. In order to reach a synthesis of the different parts of a
      project, it is important that the project is well organised and there is
      participation of researchers with both specialised insight and researchers with a
      more broad insight in the problems. It is also important that the integration
      process is balanced, and not too many research disciplines are included in the
      same project.

PMID- 15259782
TI  - Medication of production animals--cure of malfunctioning animals or production
      systems?
AB  - Medication is used in all intensive animal productions. However, the increasing
      problems with resistant bacteria in all animal productions and in humans are
      supported by a number of reports. Special attention is given to the risk for
      transmitting food-borne (multi) resistant zoonotic agents to humans due to
      failure in antibiotic treatment resulting in lower cure rates or higher case
      fatality rates. The use of medication in humans per se is capable of selecting
      for resistance in human pathogens. Nevertheless, the amount of used
      medication/antimicrobials in treatment of Danish production animals goes far
      beyond the amount used for human consumption. The increase in consumption has not
      been followed by a similarly increased mortality, e.g. illustrated by the number
      of rendered animals, increased use of injection medicine for veterinary
      treatments of diseased animals, or increased number of remarks on the carcasses
      from the slaughterhouses. Medication in animal production is facing its limits
      and relevant economic alternatives have to be developed. The strategy for the
      future must concentrate on using medication only for clinically diseased animals
      and not as a strategic treatment of the whole herd in order to maximise growth
      and camouflage of suboptimal production systems and insufficient management.

PMID- 15259783
TI  - Uptake of colostral immunoglobulins by the compromised newborn farm animal.
AB  - Neonatal mortality is very high in farm animals (approximately 10%) and disease
      resistance is greatly influenced by an adequate passive immunisation just after
      birth. In piglets, foals, calves and lambs, the intestinal absorption of
      immunoglobulins from their mother's colostrum occurs mainly by a non-specific
      endocytosis of macromolecules, but the details of the absorption process, and the
      mechanisms regulating its cessation after 1-2 days of colostrum exposure, remain
      poorly understood. In both normal and 'compromised' (premature, growth-retarded,
      hypoxic, lethargic) newborn farm animals, the intestinal capacity to absorb
      macromolecules is influenced by both diet- and animal-related factors. Thus,
      macromolecule uptake is severely reduced in response to premature birth and when
      macromolecules are to be absorbed from diets other than species-specific
      colostrum. On the other hand, fetal growth retardation, in vitro embryo
      production, or a stressful birth process are unlikely to reduce the ability of
      the intestine to absorb immunoglobulins from colostrum. More knowledge about the
      diet- and animal-related factors affecting intestinal immunoglobulin uptake will
      improve the clinical care of 'compromised' newborn farm animals. The present text
      gives a brief introduction to the process of intestinal immunoglobulin absorption
      in large farm animals and describe some recent results from the author's own
      studies in pigs, calves and lambs.

PMID- 15259784
TI  - Colostrum--more than just an immunoglobulin supplier.

PMID- 15259785
TI  - Objective measurement of health pigs--application of acute phase proteins.

PMID- 15259786
TI  - Epidemiological studies based on small sample sizes--a statistician's point of
      view.
AB  - We consider 3 basic steps in a study, which have relevance for the statistical
      analysis. They are: study design, data quality, and statistical analysis. While
      statistical analysis is often considered an important issue in the literature and
      the choice of statistical method receives much attention, less emphasis seems to
      be put on study design and necessary sample sizes. Finally, a very important
      step, namely assessment and validation of the quality of the data collected seems
      to be completely overlooked. Examples from veterinary epidemiological research
      and recommendations for each step are given together with relevant references to
      the literature.

PMID- 15259787
TI  - Bovine endotoxicosis--some aspects of relevance to production diseases. A review.
AB  - This review describes some circumstances where endotoxins of gram negative
      bacteria may be related to the pathogenesis of some common production diseases.
      Decisive evidence for the pathogentical role of endotoxins remains scarce, and
      therefore an interdisciplinary background covering epidemiological, biological,
      biochemical, clinical and experimental aspects is given. Several authors have
      suggested that endotoxins play a significant role for the development of diseases
      such as laminitis, abomasal displacement, sudden death syndrome of feed-lot
      steers etc. While the biological, biochemical and clinical pictures of bovine
      endotoxicosis is quite well known, and certainly may resemble the clinical and
      biochemical pictures seen in some of the before mentioned diseases, it is however
      still not clear how or when endotoxins would gain parenteral access. This review
      describes excerpts of the biology of endotoxins, key clinical signs and the
      biochemistry associated to these. It is described how ruminal acidosis may
      facilitate the translocation of endotoxin from the intestinal/ruminal contents to
      the portal and eventually the systemic bloodstream. The function of the liver
      hence becomes central, and the role of hepatic fatty infiltration around
      parturition is discussed. The review finally suggest that acute ruminal acidosis
      may be viewed as an analogue to the human syndrome Gut-Derived Infectious Toxic
      Shock (GITS), where shock is propagated primarily by the translocation of
      bacterial endotoxin from the gut.

PMID- 15259788
TI  - Causes, risk factors, and prevention of laminitis and related claw lesions.

PMID- 15259789
TI  - Endothelium-dependent vasorelaxant effects of the aqueous extracts of the
      Eucommia ulmoides Oliv. leaf and bark: implications on their antihypertensive
      action.
AB  - The vascular effects of three extract preparations from the Chinese medicinal
      herb, Eucommia ulmoides Oliv., which is historically an active ingredient
      commonly used in antihypertensive herbal prescriptions in China, were
      investigated with isometric contraction using isolated rat aortic and dog carotid
      rings. Both aqueous extracts isolated from eucommia leaf (L) and bark (B)
      concentration dependently caused endothelium-dependent relaxation in vessels
      precontracted with 1 microM phenylephrine (PE), but the methanol extract of the
      leaf (M) had no effect. Vessels precontracted with KCl and de-endothelialized
      vessels precontracted with PE were not affected by B or L. The endothelium
      dependent relaxation evoked by B and L was either abolished or substantially
      inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB),
      indicating the involvement of the nitric oxide (NO) synthase pathway in the
      vasorelaxant action of B and L. The relaxation to the aqueous extract of eucommia
      bark was not inhibited with 1 microM atropine, but was inhibited by 3-5 mM
      tetraethylammonium (TEA) and 3 mM 4-aminopyridine. This suggests that the
      endothelium-dependent, NO-mediated relaxation evoked by the aqueous eucommia
      extracts was not mediated via the activation of endothelium muscarinic receptors
      and may involve the activation of K+ -channels. Results in this study have
      provided the first evidence on the in vitro vasorelaxant action of E. ulmoides
      Oliv. that forms the pharmacological basis for its well-documented
      antihypertensive action.

PMID- 15259790
TI  - Time-dependent lipid response on fluvastatin therapy of patients with
      hypercholesterolemia sensitive to apoE phenotype.
AB  - Sixty-seven male patients with hypercholesterolemia, divided into three groups
      according to apolipoprotein E phenotype (33 with apoE3/ 3 phenotype, E3 group; 23
      with 2/2 or 2/3, E2+ group; 11 with 4/4 or 4/3, E4+ group), received daily 20-40
      mg of fluvastatin for 12 weeks. The levels of triglyceride (TG), cholesterol
      (Chol), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein
      cholesterol (HDL-C) were measured after 0, 4, 8 and 12 weeks on fluvastatin and
      after 4 weeks washout period. Lipid percentage changes (delta) were not
      associated with apoE phenotype for any treatment time. Cholesterol decreased by
      14% after 12 weeks and HDL-C increased by 14-16% after 12 weeks for three
      phenotype groups. deltaTG, deltaChol, deltaLDL-C were associated positively,
      while negatively for deltaHDL-C, with the corresponding basal lipid values for
      the three groups. The positive deltaTG values occurred at a low basal TG0 level
      and became negative at TG0 > 1.6-1.9 mM. For E3 and E4+ groups, only a single
      parameter contributed significantly into a variation of lipid percentage changes.
      For the E2+ group, TG0 and Chol0 contributed in a reciprocal manner into
      deltaTG12/0, both positively into deltaChol8/0; Chol0 and HDL-C0 both negatively
      contributed into deltaHDL-C12/0. HDL-C0 contributed reciprocally into LDL-C
      variability for E2+ and E4+ groups. Three effects seem to contribute differently
      into lipid response among patients with different apoE phenotype: the inhibition
      of hepatic and lipoprotein lipase activities, the competition between TG-rich and
      low-density lipoproteins for LDL-receptor and the accumulation of intermediate
      density lipoproteins in patients bearing E2 isoform.

PMID- 15259791
TI  - Comparison of the in vivo coronary action of endothelin-1 and vasopressin role of
      nitric oxide and prostanoids.
AB  - To compare the coronary effects of endothelin-1 and vasopressin, as well as the
      role of nitric oxide (NO) and prostanoids in these effects, blood flow in the
      left circumflex (73 animals) or left anterior descending (19 animals) coronary
      artery (coronary flow) was electromagnetically measured, and both peptides were
      intracoronarily injected in anesthetized goats under control conditions and after
      intravenous administration of the inhibitor of NO synthesis NW-nitro-L-arginine
      methyl ester (L-NAME, 47 mg/kg, nine animals) or the inhibitor of cyclooxygenase
      meclofenamate (6-8 mg/kg, seven animals). In every animal, both endothelin-1 and
      vasopressin reduced coronary flow in a dose-dependent way, but these reductions
      by 0.03, 0.1 and 0.3 nmol of endothelin-1 (16%, 33% and 66%, respectively) were
      significantly higher than those by the equimolar doses of vasopressin (11%, 22%
      and 35%, respectively). After L-NAME treatment, the reductions of coronary flow
      by both peptides were augmented, and this augmentation was about two times higher
      for endothelin-1 than for vasopressin. Meclofenamate treatment did not affect the
      reductions of coronary flow caused by both peptides. Therefore, we suggest that
      endothelin-1 is more effective than vasopressin for producing coronary
      vasoconstriction, but vasopressin also produces remarkable coronary
      vasoconstriction. Also, it is suggested that NO may play a more relevant role for
      modulating the coronary vasoconstriction by endothelin-1 than by vasopressin, and
      that cyclooxygenase products may not be involved in the coronary effects of these
      two peptides.

PMID- 15259792
TI  - Omapatrilat increases renal endothelin in deoxycorticosterone acetate-salt
      hypertensive rats.
AB  - Vasopeptidase inhibitors are a new class of antihypertensive drugs that are
      single molecules having dual inhibitory action on angiotensin-converting enzyme
      (ACE) and neutral endopeptidase (NEP). The best known drug in this class is
      omapatrilat, which has been proposed to be more efficacious than ACE inhibitors
      because of its ability to inhibit NEP and prevent the breakdown of atrial
      peptides and bradykinin. However, survival of endothelin (ET) may also be
      enhanced and therefore, NEP inhibitors may have limited efficacy under conditions
      of low renin and high ET production. The purpose of the current study was to
      contrast the effects of the ACE inhibitor, enalapril, with omapatrilat in a model
      of established hypertension where ACE inhibitors are ineffective, the
      deoxycorticosterone acetate (DOCA)-salt-treated rat. Two weeks after starting
      DOCA-salt treatment, rats were given either enalapril (10 mg/kg/day) or
      omapatrilat (30 mg/kg/day) for 5 days. Mean arterial pressure (MAP) measured by
      radiotelemetry in untreated DOCA-salt rats increased from 102 +/- 2 to 181 +/- 12
      mm Hg (P<.05) as a result of DOCA-salt treatment for 3 weeks. MAP was unaffected
      by either enalapril (189 +/- 3 mm Hg) or omapatrilat (184 +/- 8 mm Hg). DOCA-salt
      treatment significantly increased urinary ET excretion compared to baseline (1.6
      +/- 0.2 vs. 0.5 +/- 0.1 pmol/day). Administration of omapatrilat significantly
      increased urinary ET excretion in DOCA-salt rats (2.9 +/- 0.4 pmol/day) compared
      to enalapril-treated (1.6 +/- 0.2 pmol/day) or untreated (1.5 +/- 0.1 pmol/day)
      rats. These results indicate that combined ACE/NEP inhibition does not lower
      blood pressure in a model of established hypertension with high ET activity.
      These results also support the hypothesis that combined ACE/NEP inhibition can
      increase renal ET production.

PMID- 15259793
TI  - Chronic effects of toremifene on the vasculature of menopause-induced rats.
AB  - During menopause, women have a higher propensity for developing cardiovascular
      diseases. Recent studies have shown that treatment with selective estrogen
      receptor modulators (SERMs) improves cardiovascular status in menopausal women.
      The mechanisms involved, however, have not been elucidated. The present study
      evaluates the effect of toremifene (10 mg/kg/day), a new member of SERM family,
      on the vasculature of ovariectomized (Ovx) Sprague-Dawley rats that have been
      treated with the drug for a 4-week period. Age-matched sham, Ovx-untreated, and
      Ovx 17beta-estradiol-treated rats were used as controls. Aortic rings from
      treated and untreated animals were used to determine vascular responses to
      norepinephrine, acetylcholine, and sodium nitroprusside. Systolic blood pressure
      (SBP), plasmatic nitric oxide (NO) concentration, estrogen levels, aortic wall
      thickness, and cholesterol profiles were also determined. Toremifene displaces
      the concentration-response curve (CRC) for the acetylcholine-induced relaxation
      to the left and increases the Emax by 34% (from 59.2 +/- 4.2% in Ovx-untreated to
      90.2 +/- 3.1% in Ovx-treated rats, n = 9, P < .05). Toremifene increases the Emax
      (by 22%) without modifying the EC5o for the NE-induced contraction. In addition,
      toremifene amplifies the relaxing responses to sodium nitroprusside compared to
      Ovx-untreated group (P < .05). SBP was significantly reduced in the Ovx
      toremifene-treated group when compared to the Ovx-untreated group (124 +/- 3.5 mm
      Hg for Ovx toremifene-treated vs. 161 +/- 4.3 mm Hg for Ovx-untreated, n = 10, P
      < .05). Rats treated chronically with toremifene also exhibited a significantly
      higher plasmatic NO levels, and a decrease in basal resting tension and aortic
      wall thickness. The drug, however, did not affect the plasmatic high-density
      lipoprotein (HDL)/total cholesterol ratio. These results suggest that chronic
      administration of toremifene improves cardiovascular performance in menopause
      induced rats by reversing endothelial dysfunction and decreasing vascular resting
      tone. Thus, use of toremifene may help to diminish total peripheral resistance
      and improve cardiovascular status in Ovx rats.

PMID- 15259794
TI  - Wound dis-ease.

PMID- 15259795
TI  - Dressing the discomfort: managing radiation therapy-induced dermatitis.

PMID- 15259796
TI  - United Ostomy Association issues advocacy report card.

PMID- 15259797
TI  - Individualized care.

PMID- 15259798
TI  - Spring update.

PMID- 15259799
TI  - Hemophilia and maggots: from hospital admission to healed wound.

PMID- 15259800
TI  - A retrospective evaluation of digital wound imaging to predict response to
      hyperbaric oxygen treatment.
AB  - As new wound care treatments become available, correct initial treatment
      selection and dynamic modification of regimens, based on wound response to
      treatment, must be applied to improve outcomes and reduce cost. One alternative
      is wound morphometry using digital wound images to evaluate wound response to
      treatment in realtime. To determine whether wound area measurements taken during
      the first 3 weeks of hyperbaric oxygen treatment predict eventual treatment
      response and how demographic and disease factors impact hyperbaric oxygen
      treatment response, a retrospective study using digital wound images, demographic
      data, and available clinical laboratory values was conducted. Participants
      included 29 wound care patients with nonhealing wounds of the lower extremities
      receiving treatment at a hyperbaric wound care facility. Conventional wound care
      (ie, debridement, dressing changes, and topical agents) plus hyperbaric oxygen
      treatment (100% oxygen breathing at 2.4 atmospheres absolute for 90 minutes)
      given once every weekday for up to 20 weeks was provided. Graphical analysis of
      normalized wound area over time revealed two groups: minimal responders (n=13)
      and robust responders (n=16). Minimal response was characterized by delayed onset
      of wound area reduction and virtual cessation of reduction by week 3. Robust
      response was continuous, sustained, and resulted in average wound area reduction
      of 80% by end of treatment, compared to 47% in minimally responsive patients.
      Age, blood glucose, and serum creatinine significantly affected the wound healing
      response to hyperbaric oxygen treatment (P<0.05). Digital images obtained during
      the first 3 weeks of treatment predicted if a patient is minimally responsive to
      hyperbaric oxygen treatment with 100% accuracy. Area measurements obtained in
      this manner can be used to identify patients minimally responsive to hyperbaric
      oxygen treatment, enabling rapid assessment of treatment response to make timely
      changes in therapy in order to optimize treatment outcomes.

PMID- 15259801
TI  - Lateral rotation mattresses for wound healing.
AB  - Continuous lateral rotation therapy utilizes mattresses and beds that move the
      patient in a regular pattern around a longitudinal axis. Although these devices
      have been used for several decades for other medical purposes, literature is
      scant regarding their role in the treatment of skin breakdown in the bedridden,
      difficult-to-reposition patient. A descriptive study was undertaken to ascertain
      the rate of wound healing and number of weeks to achieve wound closure when
      continuous lateral rotation therapy was employed in patients with partial
      thickness (n=10) and full-thickness (n=20) ulcers on the trunk or pelvis.
      Patients receiving the services of Advanced Therapy Surfaces in home or long-term
      care between March 15, 2002 and April 1, 2003 were enrolled. Partial-thickness
      wounds healed at an average rate of 16.68% per week, with an average time for
      continuous lateral rotation therapy of 9.25 weeks. Full-thickness wounds healed
      at an average rate of 14.38% per week (time to healing 11.25 weeks). No
      additional areas of skin breakdown were observed. These encouraging results
      suggest that additional research is warranted.

PMID- 15259802
TI  - Mysterious calciphylaxis: wounds with eschar--to debride or not to debride?
AB  - Calciphylaxis is a confusing disease process that affects people with end-stage
      renal disease. The prognosis of this increasingly common condition is poor and
      mortality rates range from 60% to 80% related to wound infection, sepsis, and
      organ failure. Its presenting sign is skin necrosis related to calcification of
      the arteriole microvasculature. The disease is painful and debilitating,
      particularly due to the necrotic wounds. Aggressive wound care to prevent
      infection is vital when eschar does not protect the wound and drainage is
      present, but debridement is contraindicated for wounds covered with dry,
      noninfected eschars. The decision to debride is based on the patient's total
      clinical picture. Patients with calciphylaxis have poor healing potential due to
      ischemia and comorbidity factors such as diabetes mellitus, peripheral vascular
      disease, and obesity. The goal of care is prevention of infection and pain
      management. Some of the sensitizers and challengers responsible for the chemical
      imbalance leading to the arteriole calcification, as well as risk factors and
      clinical manifestations of calciphylaxis, are reviewed. A discussion of treatment
      focuses on wound care of stable necrotic ulcers and a case report illustrating
      the progression of calciphylaxis is presented.

PMID- 15259803
TI  - New techniques in image-guided percutaneous biopsy.
AB  - Image-guided percutaneous biopsy is a well-established and safe technique for
      obtaining tissue specimens from various regions of the body and plays a crucial
      role in patient management. Improvements in needle designs, development of new
      biopsy techniques, and continual advances in image-guidance technology have
      improved the safety and efficacy of the procedure. Lesions previously considered
      relatively inaccessible can now be safely biopsied. This review looks at the
      recent technologic developments in image guidance for percutaneous biopsy
      procedures. Improvements in needle design and other innovations intended to
      enhance the diagnostic yield of biopsy specimens are briefly discussed. Also
      described are some new techniques and unconventional approaches that help provide
      safe access to difficult-to-reach lesions.

PMID- 15259804
TI  - Vascular radiology in trauma.
AB  - It's been 30 years since an endovascular technique to control traumatic
      hemorrhage was first described. Despite major technical advances in both
      diagnostic and therapeutic technology, and a great deal of experience since then,
      endovascular techniques are rarely considered as part of frontline management for
      vascular trauma. This review considers the literature and calls for better
      planning and implementation of diagnostic and image-guided therapeutic
      facilities. Endovascular techniques should be an essential part of vascular
      trauma management along with endovascular specialists, partners in trauma teams.

PMID- 15259805
TI  - Primary stenting of focal atherosclerotic infrarenal aortic stenoses: long-term
      results in 13 patients and a literature review.
AB  - We conducted this study to investigate the value of primary stent implantation
      for the endovascular treatment of focal atherosclerotic stenoses of the
      infrarenal abdominal aorta. The data of 13 patients with a localized complex
      infrarenal aortic stenosis who underwent primary stenting was retrospectively
      evaluated. The patients (6 females, 7 males) had a mean age of 57.3 +/- 9.1 years
      (mean +/- SD). In all patients, the aortic diameter was measured on CT sections,
      and a self-expanding endoprosthesis was primarily implanted followed by
      dilatation with single or double balloons. In 3 patients, additional distal
      stenoses were also endovascularly treated. The procedure was technically
      successful in all patients. No complications occurred except for 2 minor groin
      hematomas. During the 43 +/- 23 months (mean +/- SD) follow-up (range: 12-96
      months), all stented aortic segments remained patent. Clinical patency was lost
      in 4 patients, which was due to atherosclerosis or restenosis distal to the
      aorta. In view of the excellent early and long-term results, we believe that
      primary stenting should be considered the first line treatment in properly
      selected patients with focal atherosclerotic infrarenal stenoses of the abdominal
      aorta.

PMID- 15259806
TI  - Clinical outcome after intrahepatic venous stent placement for malignant inferior
      vena cava syndrome.
AB  - We evaluated the clinical outcome of malignant inferior vena cava (IVC) syndrome
      after intrahepatic IVC stent placement by retrospective analysis of 50
      consecutive patients (25 men, 25 women, age 32-83 years) with malignant IVC
      syndrome who were treated with intrahepatic stent placement. Gianturco-Rosch-Z
      (GRZ) stents (n = 45), and Wallstents (n = 5) were inserted. Clinical outcome was
      assessed from patients' records using a score based on leg swelling,
      scrotal/vulvar edema, ascites and anasarca before and after stent placement, as
      well as at last follow-up visit before death. Clinical follow-up was supplemented
      by duplex sonography in 36 patients. Inferior venocavography was performed in 5
      patients prior to re- intervention. Follow-up time ranged from 1 to 932 days
      (mean 62 days). Mean pressure gradient in the IVC was reduced from 14 +/- 4.1
      mmHg before to 2.9 +/- 3.2 mmHg after stent placement (p < 0.001). Four patients
      had stent occlusion, 2 of whom were successfully re-stented. Primary and
      secondary patency was 59% and 100%, respectively at 540 days. Immediate clinical
      data were available in 44 patients: 38 improved; 6 did not respond. Last follow
      up visit data were available in 36 patients: 24 showed persistent symptom relief
      till death. All symptom scores were significantly improved after stent placement
      (p < 0.001) and with the exception of ascites, remained significantly improved (p
      < 0.05) until the last follow-up. Increased serum bilirubin was a common
      characteristic of clinical failures and recurrences. Intrahepatic IVC stent
      placement resulted in significant symptomatic relief in patients with malignant
      IVC syndrome. Palliation was effective even in patients with a very short life
      expectancy.

PMID- 15259807
TI  - Incidence of important hemobilia following transhepatic biliary drainage: left
      sided versus right-sided approaches.
AB  - Our purpose here is to describe our experience with important hemobilia following
      PTBD and to determine whether left-sided percutaneous transhepatic biliary
      drainage (PTBD) is associated with an increased incidence of important hemobilia
      compared to right-sided drainages. We reviewed 346 transhepatic biliary drainages
      over a four-year period and identified eight patients (2.3%) with important
      hemobilia requiring transcatheter embolization. The charts and radiographic files
      of these patients were reviewed. The side of the PTBD (left versus right), and
      the order of the biliary ductal branch entered (first, second, or third) were
      recorded. Of the 346 PTBDs, 269 were right-sided and 77 were left-sided. Of the
      eight cases of important hemobilia requiring transcatheter embolization, four
      followed right-sided and four followed left-sided PTBD, corresponding to a
      bleeding incidence of 1.5% (4/269) for right PTBD and 5.2% (4/77) for left PTBD.
      The higher incidence of hemobilia associated with left-sided PTBD approached, but
      did not reach the threshold of statistical significance (p = 0.077). In six of
      the eight patients requiring transcatheter embolization, first or second order
      biliary branches were accessed by catheter for PTBD. All patients with left-sided
      bleeding had first or proximal second order branches accessed by biliary drainage
      catheters. In conclusion, a higher incidence of hemobilia followed left-versus
      right-sided PTBD in this study, but the increased incidence did not reach
      statistical significance.

PMID- 15259808
TI  - Are TIPS stent-grafts a contraindication for future liver transplantation?
AB  - Our purpose was to assess the feasibility of orthotopic liver transplantation
      (OLT) in patients priorly having undergone transjugular intrahepatic
      portosystemic shunt (TIPS) with an expanded tetrafluoroethylene (e-PTFE)-covered
      endoprosthesis. In 48 patients an e- PTFE-covered endoprosthesis was inserted to
      treat severe complications of portal hypertension. In 36 patients the
      endoprosthesis was inserted during TIPS creation (de novo TIPS); in the other 12
      patients the endoprosthesis was placed to repermeabilize the previously created,
      but occluded bare stent (revision TIPS). Eight of them (5 de novo and 3 revision
      cases) later underwent an OLT. The hospital records of these patients were
      reviewed from initial admission, through TIPS, the pre-OLT period, and OLT to
      current postoperative status. Five de novo and 3 revision cases underwent OLT 4
      279 days (mean delay: 80.8 days) after TIPS procedure. All OLT's were performed
      under veno-venous bypass surgery. De visu surgical inspection confirmed correct
      positioning of the fully patent stent graft, starting in the portal vein and
      ending at the junction of the hepatic vein to the inferior caval vein. No
      surgical difficulty was observed during proximal or distal clamping or during
      resection of the diseased liver. Correctly positioned e-PTFE-covered nitinol
      endoprostheses do not interfere with a later OLT and may not be considered as a
      contraindication in patients who need a TIPS as a bridge to OLT.

PMID- 15259809
TI  - Resolved abdominal aortic aneurysms following stent graft treatment: a report of
      five cases.
AB  - Complete aneurysm resolution is the hallmark of successful endoluminal stent
      graft treatment. We describe 5 patients in whom an abdominal aortic aneurysm
      (AAA) disappeared completely at mid-term follow-up after endovascular stent-graft
      placement. We reviewed 45 patients (43 men and 2 women) who underwent AAA repair
      using an endovascular technique, from April 1997 to December 2001. Mean AAA
      diameter was 58.3 mm. On 48-month follow-up, 12 aneurysms had not changed in
      size, 4 had grown, 16 had shrunk, and 5 had resolved completely. We describe
      these 5 patients in detail. The 5 patients were all men, mean age 68 years: their
      mean aneurysmal sac diameter was 54 mm. The only common finding in all of them
      was patency of lumbar and inferior mesenteric arteries at pre-procedure
      evaluation as well as at follow-up. Mean time to complete resolution was 18
      months. No major complications were encountered. AAA may resolve completely after
      endovascular stent-graft implantation. Patent side branches may perhaps
      contribute to AAA disappearance by antegrade flow. A larger patient population
      should be reviewed, however, before any statistical conclusion can be drawn.

PMID- 15259810
TI  - Use of a mixture of gadolinium and iodinated contrast for angiography.
AB  - The purpose of this study was to determine if the image quality of gadolinium
      digital subtraction angiography (DSA) can be improved by the addition of small
      quantities of iodinated contrast to gadolinium. The optical density (OD) of a
      mixture of four parts gadolinium-based contrast to one part iodinated contrast
      was measured through a phantom study and compared to that of full-strength
      gadolinium, full strength iodinated contrast, and a 20% solution of iodinated
      contrast. We also compared the clinical image quality of the mixture of
      gadolinium-based contrast and iodinated contrast relative to full-strength
      gadolinium and full strength iodinated contrast during DSA. The DSA image quality
      of the gadolinium-iodinated contrast mixture was significantly improved relative
      to images obtained with full-strength gadolinium and compared favorably to that
      obtained with full-strength iodinated contrast. The phantom data showed that the
      OD of the gadolinium-iodinated contrast mixture was much greater than that of
      full strength gadolinium and the 20% iodinated contrast solution. The increase in
      OD was greater than that expected from a simple additive effect of the OD of the
      contrast agents. Adding a small amount of iodinated contrast to gadolinium
      results in a significant improvement in the radiographic density and DSA image
      quality of gadolinium. This simple technique appears to overcome one of the major
      limitations of gadolinium-based angiography-poor radiographic density-while
      continuing to minimize the volume of administered iodinated contrast.

PMID- 15259811
TI  - Combined therapy of radiofrequency ablation and ethanol injection of rabbit
      liver: an in vivo feasibility study.
AB  - Our purpose was to compare the effects of percutaneous radiofrequency ablation
      (RFA) combined with percutaneous ethanol injection (PEI) on the extent of
      ablation in in vivo rabbit liver tissue as compared with either therapy alone.
      Twenty-two New Zealand white rabbits were included in this study and allocated
      into three groups: group A: conventional RFA (n = 6); group B: PEI (n = 6): group
      C: combined RFA and PEI (n = 10). For combined RFA and PEI, under ultrasound
      guidance, 1 mL of absolute ethanol was injected into the target area of the liver
      parenchyma through a 21-gauge Chiba needle before performing RFA. RFA was
      performed using a 17-gauge internally cooled electrode with 1-cm active tip, and
      RF energy (30 W) was applied for 3 minutes, with or without ethanol injection.
      After RFA or PEI, contrast-enhanced computed tomography and CT-pathologic
      correlation were performed. The short-axis and long-axis diameters of thermal
      lesions of each group were compared. All procedures were technically successful
      and a total of 38 lesions were produced. The mean short-axis and long-axis
      diameter of the coagulation necrosis in rabbits of group C (combination of RFA
      and PEI), were significantly larger than those of other groups: group A: 10.3 +/-
      2 mm and 11.4 +/- 2 mm: group B: 3.1 +/- 1 mm and 4.3 +/- 2 mm: group C: 12.8 +/-
      3 mm and 17.8 +/- 6 mm (p < 0.05). On contrast-enhanced CT scan, the lesions of
      rabbits of the group C appeared to be more frequently irregular compared to those
      of group A (20% in group A vs. 67% in group C). There were three complications
      including two localized hematomas and one cardiopulmonary failure. Combined RFA
      and PEI could increase the dimension of coagulation necrosis without increasing
      complications and therefore, may be successfully used for treating larger
      lesions.

PMID- 15259813
TI  - Reasonable safety ranges.

PMID- 15259812
TI  - Response of balloon-expandable endoprosthetic metallic stents subjected to over
      expansion in vitro.
AB  - We attempted to evaluate the in vitro behavior and performance of balloon
      expandable endoprosthetic metallic stents subjected to over-expansion (OE).
      Seventy-two balloon-expandable endoprosthetic stents, representing 22 models from
      six manufacturers, were overexpanded in vitro. Stents were initially expanded to
      their maximum manufacturer- recommended diameter and then over-expanded
      incrementally to their endpoints. Endpoints for OE were either stent
      disarticulation or an inability to undergo further expansion despite balloon
      insufflation to maximum burst pressure. Measurements of stent dimensions were
      recorded at each overexpanded diameter and comparisons were made to
      manufacturer's specifications. A total of 288 balloon-driven expansions were
      performed on 72 stents. Sixteen stents were expanded to large diameters (> or =
      16 mm), 20 stents underwent OE of 50% or greater. One model tended to
      disarticulate after OE greater than 50%. There were five models that had a
      tendency to disarticulate after minimal OE. Five models were resistant to OE (25%
      or less OE) but did not disarticulate. Nearly all stents showed some degree of
      foreshortening with OE, while 36 stents underwent foreshortening of 30% or more.
      Models that are not recommended for OE include Intrastent, Intrastent
      DoubleStrut, NIR Royale and Omniflex. Good candidates for OE include Intrastent
      DoubleStrut LD, Palmaz large, Medtronic Extra Support Biliary Plus and Medtronic
      Flexible Biliary. Palmaz XL remains the only model available for expansion from
      20 to 28 mm in diameter. For the remaining stents, OE is possible, however,
      caution should be used.

PMID- 15259814
TI  - Nuts and bolts count, too!

PMID- 15259815
TI  - Rupture of true aneurysms of the pancreaticoduodenal arcade: treatment with
      transcatheter arterial embolization.
AB  - We present 2 cases of ruptured true aneurysms of the pancreaticoduodenal arcade,
      underscoring the role of transcatheter arterial embolization (TAE) as the initial
      treatment of choice in pancreaticoduodenal arcade aneurysm. Ruptured true
      aneurysms of the pancreaticoduodenal artery (PDA) are uncommon and few cases have
      been reported, whereas false aneurysms are seen more often. The first patient we
      describe is a 63-year-old woman with an aneurysm of the PDA initially treated by
      TAE. The second case is a 67-year-old woman with an aneurysm of the inferior PDA
      post-operatively treated by TAE. In both patients TAE via a combined superior
      mesenteric artery and celiac axis approach was successful. Follow-up contrast
      enhanced computed tomography showed prolonged occlusion of both aneurysms. A
      review of the literature concerning TAE supports our experience that TAE of
      ruptured aneurysms of the pancreaticoduodenal arcade, when feasible, is at least
      as effective as conventional surgery, but with lower morbidity and mortality.
      Therefore, TAE should be the initial treatment of choice in this group of
      patients.

PMID- 15259816
TI  - Transcatheter arterial embolization for large pancreaticoduodenal artery aneurysm
      with mechanically detachable coils.
AB  - Large aneurysms (5.5 and 3.6 cm in diameter) arising from the inferior
      pancreaticoduodenal artery located just near the main superior mesenteric artery
      were incidentally diagnosed in two patients. Transcatheter arterial embolization,
      packing mechanically detachable coils and microcoils into the aneurysms, was
      performed while the inflated balloon catheter was placed near the neck of the
      aneurysms. The procedures were successfully performed and no aneurysmal rupture
      or bowel ischemia was noted during follow-up. Balloon-assisted transcatheter
      arterial embolization with mechanically detachable coils seems to be an effective
      and safe treatment for large inferior pancreaticoduodenal aneurysms.

PMID- 15259817
TI  - Transhepatic embolization of a recanalized congenital hepatic arterioportal
      fistula with NBCA and coils.
AB  - Congenital hepatic arterioportal fistula is a treatable cause of portal
      hypertension. Transarterial embolization is a widely accepted endovascular
      treatment approach. Here, a case of a recanalized congenital hepatic
      arterioportal fistula after prior transarterial coil embolization that was
      successfully treated with percutaneous transhepatic embolization with coils and N
      butyl 2-cyanoacrylate is reported. The percutaneous transhepatic approach can be
      an effective alternative for patients with recanalized hepatic arterioportal
      fistula who have undergone prior transarterial coil embolization, and N-butyl 2
      cyanoacrylate can be used as an embolic material in addition to metallic coils to
      achieve quick and total occlusion.

PMID- 15259818
TI  - Aortopulmonary window: a rare adult case demonstration by echocardiography, MRI,
      CE-MRA and angiography.

PMID- 15259819
TI  - Computed tomographic findings of syphilitic aortitis.
AB  - We describe the computerized tomographic (CT) findings of the aortic wall in a
      case of acute-phase syphilitic arteritis. The delayed phase of the contrast
      enhanced CT shows a double-ring configuration of the thick thoracic aortic wall,
      which is similar to CT findings previously reported for Takayasu arteritis. We
      speculate that the resemblance of the CT findings for these two diseases accounts
      for their similar histopathological features.

PMID- 15259820
TI  - Carotid-carotid bypass prior to endoluminal exclusion in a patient with acute
      type B aortic dissection.

PMID- 15259821
TI  - Transcatheter embolization of pulmonary artery false aneurysm associated with
      primary pulmonary hypertension.
AB  - A 29-year-old woman with primary pulmonary hypertension presented with recurrent
      hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass
      surrounded by consolidation related to parenchymal hemorrhage. Pulmonary
      angiography suggested that the mass was a pulmonary artery false aneurysm. After
      a microcatheter was superselectively inserted into the parent artery of the false
      aneurysm, the false aneurysm was successfully treated by transcatheter
      embolization with coils. Her hemoptysis has never recurred.

PMID- 15259822
TI  - Primary cardiac lymphoma: helical CT findings and radiopathologic correlation.

PMID- 15259823
TI  - Schizophrenia and theory of mind.

PMID- 15259824
TI  - Social cognition, brain networks and schizophrenia.
AB  - BACKGROUND: A better understanding of the neural basis of social cognition
      including mindreading (or theory of mind) and empathy might help to explain some
      deficits in social functioning in people with schizophrenia. Our aim was to
      review neuroimaging and neuropsychological studies on social cognition, as they
      may shed light on the neural mechanisms of social cognition and its dysfunction
      in patients with schizophrenia. METHOD: A selective literature review was
      undertaken. RESULTS: Neuroimaging and neuropsychological studies suggest
      convergence upon specific networks for mindreading and empathy (the temporal
      cortex, amygdala and the prefrontal cortex). The frontal lobe is likely to play a
      central role in enabling social cognition, but mindreading and empathic abilities
      may require relatively different weighting of subcomponents within the same
      frontal-temporal social cognition network. CONCLUSIONS: Disturbances in social
      cognition may represent an abnormal interaction between frontal lobe and its
      functionally connected cortical and subcortical areas. Future studies should seek
      to explore the heterogeneity of social dysfunction within schizophrenia.

PMID- 15259825
TI  - Do people with schizophrenia display theory of mind deficits in clinical
      interactions?
AB  - BACKGROUND: Having a 'theory of mind' (ToM) means that one appreciates one's own
      and others' mental states, and that this appreciation guides interactions with
      others. It has been proposed that ToM is impaired in schizophrenia and
      experimental studies show that patients with schizophrenia have problems with
      ToM, particularly during acute episodes. The model predicts that communicative
      problems will result from ToM deficits. METHOD: We analysed 35 encounters (> 80 h
      of recordings) between mental health professionals and people with chronic
      schizophrenia (out-patient consultations and cognitive behaviour therapy
      sessions) using conversation analysis in order to identify how the participants
      used or failed to use ToM relevant skills in social interaction. RESULTS:
      Schizophrenics with ongoing positive and negative symptoms appropriately reported
      first and second order mental states of others and designed their contributions
      to conversations on the basis of what they thought their communicative partners
      knew and intended. Patients recognized that others do not share their delusions
      and attempted to reconcile others' beliefs with their own but problems arose when
      they try to warrant their delusional claims. They did not make the justification
      for their claim understandable for their interlocutor. Nevertheless, they did not
      fail to recognize that the justification for their claim is unconvincing.
      However, the ensuing disagreement did not lead them to modify their beliefs.
      CONCLUSIONS: Individuals with schizophrenia demonstrated intact ToM skills in
      conversational interactions. Psychotic beliefs persisted despite the realization
      they are not shared but not because patients cannot reflect on them and compare
      them with what others believe.

PMID- 15259826
TI  - North Wales randomized controlled trial of cognitive behaviour therapy for acute
      schizophrenia spectrum disorders: outcomes at 6 and 12 months.
AB  - BACKGROUND: Recent reviews of randomized controlled trials have concluded that
      cognitive behaviour therapy (CBT) is effective, as an addition to standard care,
      in the treatment of people suffering from schizophrenia. Most of the trials have
      been conducted with stabilized out-patients. The aim of this trial was to
      evaluate the effectiveness of CBT for in-patients suffering acute psychotic
      episodes, when delivered under conditions representative of current clinical
      practice. METHOD: Consecutive admissions meeting criteria were recruited. After
      screening, 43 were assigned at random to a treatment-as-usual (TAU) control group
      and 47 were assigned to TAU plus CBT. At baseline, 6 months and 12 months,
      patients were rated on symptoms and social functioning. CBT (maximum 25 sessions)
      began immediately after baseline assessment. RESULTS: The CBT group gained
      greater benefit than the TAU group on symptoms and social functioning. A larger
      proportion of the CBT group (60%) than the TAU group (40%) showed reliable and
      clinically important change, and none of them (v. 17%) showed reliable
      deterioration compared with baseline. CONCLUSIONS: CBT for patients suffering
      acute psychotic episodes can produce significant benefits when provided under
      clinically representative conditions.

PMID- 15259827
TI  - A randomized controlled trial of a brief intervention for families of patients
      with a first episode of psychosis.
AB  - BACKGROUND: Carers' satisfaction with psychiatric services related to information
      and advice is generally poor. This may be particularly true for services trying
      to meet the needs of ethnically diverse communities. It is important that
      services attempt to ameliorate carers' concerns as early as possible. The authors
      aimed to assess the impact of a brief educational and advice support service on
      carers of patients with a first episode of psychotic illness. METHOD: Carers of
      all patients identified with a first episode of psychosis in a defined
      psychiatric catchment area of North London were invited to participate. Following
      consent from patients and relatives, relatives were randomly allocated to receive
      (in addition to usual services) a brief intervention comprising education and
      advice about the disorder from a support team or to usual care from community
      psychiatric services. RESULTS: One hundred and six carers were recruited to the
      study. Take-up of the intervention was less than expected and the intervention
      had little impact. The authors found no differences over time between the
      randomized arms for relatives' satisfaction (F = 23, p = 0 .4, df = 1) or number
      of days spent by patients in hospital over nine months from entry to the trial
      (F= 1.7, p= 0.18, df = 1). CONCLUSIONS: It was found that the support and advice
      intervention for families had little impact on their satisfaction or on patients'
      outcomes. However, failure to take up the intervention threatens the conclusions
      as the power to show an effect was reduced. Although family interventions, in
      general, are considered an important adjunct to the treatment of patients with
      chronic psychosis, there may be difficulties in providing an educational and
      support intervention shortly after first onset. How and when psychiatric services
      provide information and advice to carers of people newly diagnosed with a
      psychosis requires further study.

PMID- 15259828
TI  - Characteristics and circumstances of homicidal acts committed by offenders with
      schizophrenia.
AB  - BACKGROUND: While men with schizophrenia are at higher risk of displaying
      homicidal behaviours compared with the general population, very little is known
      about the circumstances related to the triggering of such violent acts among
      offenders with schizophrenia. The main goal of the present investigation was to
      describe the surrounding context, psychotic symptoms, target characteristics and
      other circumstantial factors associated with homicidal acts committed by men with
      schizophrenia, with or without an additional antisocial personality disorder
      (APD). METHOD: Comprehensive clinical and research interviews, as well as
      multiple sources of information including reports from social workers and police
      officers, criminal records, witness statements and questionnaires completed by
      friends, acquaintances and family members were used to determine specific
      characteristics surrounding the homicidal acts. RESULTS: Overall, a significant
      majority of homicides were considered as the consequence of psychotic symptoms;
      they mostly involved someone who knew the offender; and they usually occurred in
      a private residence. However, the subgroup of offenders with both schizophrenia
      and APD were less likely to be judged as responding to psychotic symptoms; they
      assaulted a non-relative more frequently, and they were more likely to have used
      alcohol and to be involved in an altercation with the victim prior to the
      incident than offenders without APD. CONCLUSION: Even for such extreme acts as
      homicides, the circumstances affecting the occurrence of violence among offenders
      with schizophrenia may differ when an additional APD diagnosis is present, which
      would have important implications for prevention and treatment programmes.

PMID- 15259829
TI  - Cognitive test performance in relation to psychotic symptoms and paranoid
      ideation in non-demented 85-year-olds.
AB  - BACKGROUND: Clinical studies suggest that psychotic and paranoid states in late
      life are associated with cognitive dysfunction. However, it is not clear whether
      this finding would be observed in general population samples of non-demented
      elderly, particularly after adjustment for potential confounding factors. METHOD:
      A representative sample of non-demented 85-year-olds living in the community or
      in institutions in Goteborg, Sweden (N = 347) was examined using a psychiatric
      and physical examination (including a medical history), key-informant interview,
      psychometric testing and review of medical records. Individuals with psychotic
      symptoms and paranoid ideation were compared with the mentally healthy regarding
      tests of verbal ability, inductive logical reasoning, spatial ability, perceptual
      speed, basic arithmetic, primary memory and secondary memory. RESULTS: Non
      demented 85-year-olds with psychotic symptoms or paranoid ideation performed
      specifically worse on tests measuring verbal ability, logical reasoning and two
      tests of spatial ability after adjustment for sex, education, hearing impairment,
      visual deficits, somatic disorders, depression, 3-year-mortality rate and
      incident dementia. CONCLUSIONS: Psychotic symptoms and paranoid ideation were
      associated with lower performance on cognitive tests related to verbal ability,
      logical reasoning and spatial ability in non-demented 85-year-olds after
      adjustment for potential confounders.

PMID- 15259830
TI  - Smooth pursuit deficits in schizophrenia, affective disorder and obsessive
      compulsive disorder.
AB  - BACKGROUND: In schizophrenia, affective disorders, and obsessive-compulsive
      disorder (OCD) dysfunction of frontal neuronal circuits has been suggested. Such
      impairments imply corresponding oculomotor deficits. METHOD: Eye movement
      response to foveofugal and foveopetal step-ramp stimuli was recorded within the
      same study design in patients with schizophrenia (N= 16), affective disorder (N=
      15), and OCD (N= 18) and compared with controls (N=23) using infra-red reflection
      oculography. RESULTS: In the foveofugal task steady-state velocity was lower in
      all patient groups compared with controls. Post-saccadic eye velocity was also
      decreased in patients with schizophrenia and affective disorder. In the
      foveopetal stimulus steady-state velocity was reduced in schizophrenic patients,
      only. Changes of saccadic latencies or position errors were not found in any of
      the patient groups. Also, pursuit latency was unchanged and initial eye
      acceleration was not decreased. CONCLUSIONS: Unaltered saccadic parameters
      indicate intact motion perception in cortical visual area V5. Therefore, the
      observed deficit of pursuit maintenance implies a dysfunction of frontal networks
      in all patient groups including the pursuit region of the frontal eye field
      (FEF). In patients with schizophrenia and affective disorder reduced post
      saccadic pursuit initiation may indicate an impaired interaction between the
      pursuit and the saccadic system.

PMID- 15259831
TI  - Is the female preponderance in major depression secondary to a gender difference
      in specific anxiety disorders?
AB  - BACKGROUND: While a female preponderance in unipolar depression is a consistent
      finding in community-based studies, determinants remain speculative. This study
      aimed to examine whether a female preponderance in certain anxiety disorders
      drives a gender difference in depression. METHOD: The relevant data from the
      National Comorbidity Study (NCS) are analysed. RESULTS: We observed a biphasic
      pattern in the emergence of a female preponderance in the depressive and anxiety
      disorders, with an initial pre-pubertal or early adolescent onset, and after
      attenuation in early to middle adulthood, re-emergence in mid- to late-adulthood.
      Analyses focused on determinants of the initial female preponderance. Female
      gender, presence of an anxiety disorder and variable ages of onset in the anxiety
      disorder all contributed to the increased chance of an initial depressive
      episode. Some specificity in linking the onset of depressive temporally in early
      adolescence with two anxiety disorders was demonstrated, specifically generalized
      anxiety disorder and panic disorder. CONCLUSIONS: The separate anxiety disorders
      and their age of onset had variable links with depression, but female gender
      remained a significant predictor of depression after accounting for the effects
      of prior anxiety.

PMID- 15259832
TI  - Gender differences in heritability of depressive symptoms in the elderly.
AB  - BACKGROUND: The present study aimed to investigate the relative importance of
      genetic and environmental influences on depressive symptoms in the elderly.
      METHOD: Depressive symptoms were assessed through the Center for Epidemiological
      Studies-Depression (CES-D) scale. The CES-D scale was administered to 959 twin
      pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male
      DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A
      dichotomous depressed state variable was constructed based on CES-D cut-offs and
      self-reported use of antidepressant medication. Structural equation models were
      fitted to the data to dissect genetic and environmental variance components.
      RESULTS: The sex-specific heritability estimates for depressive symptoms were 14%
      for males and 29% for females and 23% when constrained to be equal for men and
      women. The prevalence of clinically significant depressive symptoms was 16% for
      men and 24% for women. Heritability estimates for the dichotomous depressed state
      measure were 7% for males and 49% for females in the full model and 33% when
      constrained to be equal. CONCLUSION: Our results suggest that depressive symptoms
      in the elderly are moderately heritable, with a higher heritability for women
      than men, although differences in heritability estimates were not statistically
      significant.

PMID- 15259833
TI  - Cortisol does not mediate the suppressive effects of psychiatric morbidity on
      natural killer cell activity: a cross-sectional study of patients with early
      breast cancer.
AB  - BACKGROUND: There is evidence that depression impairs natural killer cell
      activity (NKA); this could have implications for anti-tumour immunity. Our aim
      was to examine the role of the hypothalamic-pituitary-adrenal (HPA) axis in
      suppressing NKA in a population of patients with early breast cancer, screened
      for depression. Secondary aims were to study the relationship between
      psychological, endocrine and immune variables and baseline tumour
      characteristics. METHOD: A cross-sectional population of female patients (n=55)
      with early breast cancer was sampled prior to primary surgery. Structured
      interview and psychometric instruments measured psychological distress. Flow
      cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for
      use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning
      saliva samples were collected to measure free cortisol levels. Tumour
      characteristics were obtained from hospital laboratory data. RESULTS: A high rate
      of psychological morbidity (40%) was observed in the population. NKA was reduced
      in those with past or current psychiatric illness compared to those without (344
      v. 553 LU20 and 455 v. 569 LU20 respectively, p < 0.05 for both). Cortisol was
      not related to psychological status but was modestly positively correlated to
      NKA. A positive correlation was observed between the Fighting Spirit subscale of
      the Mental Adjustment to Cancer Scale and tumour size (r=0.383, p=0.012).
      CONCLUSIONS: Our data support the evidence that psychological morbidity is
      associated with immune dysfunction; however, the most obvious candidate mediator
      of this effect, the HPA axis, does not appear responsible for this effect.
      Possible reasons for this are discussed.

PMID- 15259834
TI  - Clinical response augments NK cell activity independent of treatment modality: a
      randomized double-blind placebo controlled antidepressant trial.
AB  - BACKGROUND: Major depressive disorder (MDD) has been associated with alterations
      in immune function. Suppression of natural killer (NK) cell activity (NKCA)
      reliably characterizes immunological alterations observed in MDD. Antidepressant
      pharmacotherapy has been associated with modulation of NKCA. Previous
      investigations into antidepressant modulation of NKCA have not employed
      randomized double-blind placebo controlled designs. Thus, it is unknown whether
      treatment-associated changes in immune function are due to drug, placebo, or
      spontaneous remission effects. The present investigation examined the effect of
      antidepressant treatment on NKCA utilizing a randomized double-blind placebo
      controlled experimental design. METHOD: Patients (N = 16) met DSM-IV criteria for
      MDD and were randomly assigned to drug (N = 8; citalopram, 20 mg/day) or placebo
      (N = 8) under double-blind conditions. Severity and pattern of depressive
      symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). NK cell
      function was measured using a standard chromium-release assay and NK cell number
      assessed by flow cytometry. HDRS scores, NK cell function, and NK cell numbers
      were collected at 0, 1, 2 and 4 weeks of treatment. RESULTS: Clinical response
      was associated with augmented NKCA independent of treatment condition. Failure to
      respond to treatment resulted in significantly reduced NKCA over treatment
      interval. CONCLUSIONS: The present results suggest that alterations in the
      depressive syndrome, regardless of therapeutic modality, may be sufficient to
      modulate NKCA during antidepressant trials and thus may significantly impact on
      co-morbid health outcomes in MDD.

PMID- 15259835
TI  - The nosology of sub-acute and chronic fatigue syndromes that follow infectious
      mononucleosis.
AB  - BACKGROUND: A previous principal components analysis of symptoms occurring after
      infectious mononucleosis suggested that a discrete fatigue syndrome occurs, which
      is independent of psychiatric disorder. This work has not been replicated and no
      latent class analysis of subjects has been published. METHOD: We prospectively
      examined a cohort of 150 American primary care patients 2 and 6 months after the
      onset of corroborated infectious mononucleosis. A subset of 50 subjects was
      studied 4 years after onset. We performed principal components analyses of both
      psychological and somatic symptoms and latent class analyses of subjects.
      RESULTS: Principal components analyses consistently delineated two fatigue
      factors at 2 and 6 months and one fatigue factor at 4 years. These factors were
      separate from a mixed anxiety and depressive factor. A four-class solution for
      the latent class analyses consisted of most subjects with few symptoms, a few
      with many symptoms, a group with predominantly mood symptoms and some subjects
      with fatigue symptoms. CONCLUSIONS: The symptoms of the principal factors with
      fatigue were similar to those previously described. Both the factors and classes
      were independent of an equally delineated mood factor and class. These results
      support the existence of two discrete chronic fatigue syndromes after infectious
      mononucleosis, one of which is still demonstrable 4 years after onset.

PMID- 15259836
TI  - Association between childhood trauma and physical disorders among adults in the
      United States.
AB  - BACKGROUND: The goal of this investigation was to determine the association
      between self-reported childhood trauma and physical disorders among adults in the
      United States. METHOD: Data were drawn from the National Comorbidity Survey
      (N=5877). Multiple logistic regression analyses were used to determine the
      associations between childhood physical abuse, sexual abuse, and childhood
      neglect and the likelihood of specific physical disorders among adults. RESULTS:
      Childhood physical abuse, sexual abuse and neglect were associated with a
      statistically significantly increased risk of a wide range of physical illnesses
      during adulthood. After adjusting for demographic characteristics, lifetime
      anxiety and depressive disorders, alcohol and substance dependence, and all types
      of trauma: results showed that childhood physical abuse was associated with
      increased risk of lung disease (OR= 1.5 (1.1, 2.2)), peptic ulcer (OR= 1.5 (1.03,
      2.2)) and arthritic disorders (OR= 1.5 (1.1, 2.2)); childhood sexual abuse was
      associated with increased risk of cardiac disease (OR = 3.7 (1.5, 9.4)); and
      childhood neglect was associated with increased risk of diabetes (OR=2 2 (1.1,
      4.4)) and autoimmune disorders (OR =4.4 (1.7, 11.6)). CONCLUSIONS: Consistent
      with previous work, these results suggest that self-reported childhood trauma is
      associated with increased risk of a range of physical illnesses during adulthood.
      Future research that includes replication of these findings using prospectively
      assessed physical and mental disorders with objectively measured biological data
      using a longitudinal design, including other known risk factors for these
      diseases and more detailed information on specific forms of abuse, is needed to
      understand the potential mechanisms of these links.

PMID- 15259837
TI  - Neuroticism, a central link between somatic and psychiatric morbidity: path
      analysis of prospective data.
AB  - BACKGROUND: Neuroticism and somatic complaints are linked, and the aim of this
      study is to disentangle which mechanisms may be responsible for this association.
      METHOD: In a stratified sample of 7076 adults (18-65 years), neuroticism, 22 self
      reported chronic somatic conditions and five broad CIDI-diagnosed psychiatric
      syndromes were assessed at baseline and, in 3625 (51%) subjects, 3 years later.
      Using path analysis we examined whether neuroticism has direct links with future
      somatic morbidity and, conversely, whether morbidity at baseline is linked with
      higher neuroticism later on. RESULTS: Neuroticism at baseline is associated with
      psychiatric and somatic morbidity at follow-up after 3 years (31% and 24%,
      respectively, are direct associations, i.e. unmediated by each other or
      neuroticism at follow-up and independent of morbidity at baseline). Conversely,
      somatic and psychiatric morbidity at baseline are associated with increased
      neuroticism at follow-up (27% and 15%, respectively, are direct associations).
      CONCLUSIONS: Neuroticism raises risk for psychiatric and somatic morbidity but
      also results from them. It represents a central nexus in the process of morbidity
      accumulation.

PMID- 15259838
TI  - The relationship between social support, depression and treatment for depression
      in people with multiple sclerosis.
AB  - BACKGROUND: Studies have been fairly consistent in finding a relationship between
      social support and depression. However, little is known about the relationship
      between depression and social support in the context of treatment for depression.
      This study examined the effects of treatment for depression on social support
      among patients with multiple sclerosis (MS). METHOD: Sixty-three moderately
      depressed MS patients received 16 weeks of cognitive behaviour therapy (CBT),
      supportive expressive group psychotherapy (SEGP) or sertraline. Depression was
      measured using the Beck Depression Inventory and social support was measured
      using Arizona Social Support Interview Schedule. RESULTS: Treatment for
      depression was associated with significant increases in perceived social support,
      utilized social support and satisfaction with support, as well as reduction in
      need for emotional support. There were no significant changes in structural
      support or need for physical support. There were also no differences in change in
      social support across treatments. All changes in social support were fully
      explained by depression. Improvements in utilized social support and satisfaction
      with social support were fully mediated by improvements in depression. Baseline
      depression predicted improvements in perceived support and need for emotional
      support. CONCLUSIONS: These findings suggest that improvements in social support
      among MS patients during treatment for depression can be explained by depression.
      However, different domains of social support may be differentially sensitive to
      changes in depression.

PMID- 15259839
TI  - No evidence for links between autism, MMR and measles virus.
AB  - BACKGROUND: We examined whether, in the UK, there is an increased risk of autism
      (AD) following exposures, in early life, to: (1) wild measles; (2) live
      attenuated measles, alone or in combination as MMR; and (3) the alteration of the
      mumps strain within MMR. METHOD: We conducted time trend analyses of 2407 AD
      subjects born between 1959-93; and for comparison, 4640 Down's syndrome (DS)
      subjects born between 1966-93. Between 1968-86, we correlated variations in AD
      and DS births with wild measles incidence. Between 1959-93, we tested for abrupt
      changes in the long-term AD birth trend for the effects of introducing: (1)
      monovalent measles vaccines in 1968; (2) MMR immunization in 1988; and (3) the
      'overnight switch' from mixed use of Urabe MMR to exclusive use of Jeryl-Lynn MMR
      in 1992. Incidence rate ratios (IRRs) were used as measures of association.
      RESULTS: We found no significant association between AD births and exposure
      (prenatal and postnatal up to 18 months age) to population rates of measles
      infections, and no 'step-up' increase in AD births associated with the
      introduction of monovalent measles and MMR vaccines, and changing mumps strain.
      An unexpected reduction in AD births of 21% (95% CI 6.9-33.3%; P=0.005) among the
      post-1987 birth cohorts was detected. CONCLUSION: No increased risk of AD
      following exposures to wild measles and vaccinations with monovalent measles, and
      Urabe or Jeryl-Lynn variants of MMR was detected. The precise meaning of the
      detected AD births reduction is unclear. Our study cannot exclude rare
      complications of MMR, given its correlational design.

PMID- 15259840
TI  - Continuation cognitive-behavioural therapy maintains attributional style
      improvement in depressed patients responding acutely to fluoxetine.
AB  - BACKGROUND: Little is known about how continuation and maintenance cognitive
      behavioural therapy (CBT) influences important psychological constructs that may
      be associated with long-term outcome of major depressive disorder. The goal of
      this study was to examine whether CBT would help maintain attributional style
      changes experienced by patients during acute phase fluoxetine treatment. METHOD:
      Three hundred and ninety-one patients with major depressive disorder were
      enrolled in an open, fixed-dose 8 week fluoxetine trial. Remitters to this acute
      phase treatment (N= 132) were randomized to receive either fixed-dose fluoxetine
      (meds only) or fixed-dose fluoxetine plus cognitive-behavioural therapy
      (CBT+meds) during a 6-month continuation treatment phase. The Attributional Style
      Questionnaire (ASQ) was completed by patients at three time points - acute phase
      baseline, continuation phase baseline and continuation phase endpoint. Analysis
      of covariance was used to compare continuation phase ASQ composite score changes
      between groups. RESULTS: Patients in both treatment groups experienced
      significant gains in positive attributional style during the acute phase of
      treatment. Continuation phase ASQ composite change scores differed significantly
      between treatment groups, with the CBT + meds group maintaining acute phase
      positive attributional style changes, and the meds only group exhibiting a
      worsening of attributional style. The two treatment groups did not significantly
      differ in rates of relapse and final continuation phase visit HAMD-17 scores.
      CONCLUSIONS: In this sample, the addition of CBT to continuation
      psychopharmacological treatment was associated with maintenance of acute
      treatment phase attributional style gains. Further research is needed to evaluate
      the role of such gains in the long-term course of depressive illness.

PMID- 15259841
TI  - Results from randomized, controlled trials of the effects of cognitive
      remediation on neurocognitive deficits in patients with schizophrenia.

PMID- 15259842
TI  - [Facial nerve schwannomas. Report of a case].
AB  - Facial nerve schwannomas are relatively uncommon lesions. The clinical features
      depend upon the localization and extent of the lesion. The most common presenting
      symptom is that of a slowly progressive facial nerve palsy, because of facial
      schwannoma usually are located near the geniculate ganglion. A case of facial
      schwannoma is reported: a woman presenting a sudden facial palsy did not respond
      to medical and rehabilitation treatment. First, a Bell's palsy was diagnosed and
      then the facial nerve schwannoma with imaging techniques. A review about facial
      nerve schwannomas is reported.

PMID- 15259843
TI  - [Review of acute otomastoiditis in the paediatric population. Our cases].
AB  - The introduction of antibiotics has decreased the number of acute mastoiditis as
      complication of otitis media in children. However, this pathology still is a
      serious infection. Its incidence has increased in the last years and goes on
      getting diagnostic and therapeutic problems. We are reporting an own review about
      18 children diagnosed as acute otomastoiditis, hospitalized in a 10 years period,
      with ages between 10 months and 14 years. We have analysed different parameters
      standing out the otoscopic and radiologic findings, clinical symptoms, previous
      antibiotic treatment, type of surgical intervention performed and complications.

PMID- 15259844
TI  - [The incidence of thyroid carcinoma in Hashimoto's thyroiditis. Our experience
      and literature review].
AB  - The incidence of thyroid carcinoma in Hashimoto's thyroiditis has been widely
      debated and it is notorious in many published series. The possibility of an
      immunological and autoimmune mechanism in the etiopathogenia of papillary
      carcinomas stimulating lymphocytic infiltration has been suggested. We are
      reporting an our review of 4 cases of Hashimoto's concomitant with papillary
      thyroid carcinoma recorded between 1991 and 2001. The clinical data and
      complementary tests performed before the surgery are reported. Three patients
      were operated by total thyroidectomy and the other by hemithyroidectomy on a
      previous one whose diagnosis was malignant. We estimate the coexistence of
      papillary Ca. and Hashimoto's disease in 36.4% (4 of 11) in our case history.

PMID- 15259845
TI  - [Cervical abscess after hemithyroidectomy. An unusual complication].
AB  - Cervical abscesses secondary to hemithyroidectomy are an uncommon complication.
      We report the clinical case of a 37 years-old male, diagnosed and operated for
      nodular goiter, who suffered a paratracheal purulent collection three weeks
      later. He was reoperated by drainage of the neck abscess and antibiotic
      hospitalary treatment during 8 days. In a control CT showed an improvement
      despite the presence of a seroma on the surgical wound. Cervical exploration was
      normal two weeks later. Thyroid surgery is catalogued as clean and does requires
      antibiotic therapy. This must only be kept for cases of surgical wound infection
      or local abscess and both of them are rare in the literature.

PMID- 15259846
TI  - [Laryngeal actinomycosis].
AB  - Actinomycosis is a rare infectious disease in our practice and clinically it is
      charactherized by the presence of granulomatous lesions of subacute or chronic
      evolution. Most of the cases of actinomycosis are localised in the cervico-facial
      area, being the laryngeal one uncommon. We present a clinical case of a 53 years
      old male diagnosed of primary laryngeal actinomycosis and we realise a
      bibliographic revision on this subject emphazising the diagnosis techniques and
      the differential diagnosis of this kind of lesions.

PMID- 15259847
TI  - [Tertiary hyperparathyroidism. Report of 5 cases].
AB  - Tertiary hyperparathyroidism represents an autonomous proliferation state of the
      parathyroid glands that takes place in spite of performing a renal
      transplantation in patients with chronic renal failure due to the illness. We are
      reporting 5 own clinical cases collected in a 14 years period corresponding to 2
      men and 3 women, with ages between 43 and 53, that were sent from Nephrology for
      surgical intervention. The AP result was hyperplasia in 4 samples and 1 adenoma
      in the rest. 2 transitory hypocalcemias were registered but not recurrential
      palsies. After the surgery we got the normalization of hypercalcemia in all of
      them and improvement of skeletal symptoms.

PMID- 15259848
TI  - [Stenon or Stensen duct. How sholud we call the secretory duct of the parotid
      gland? Brief biography of its discoverer].
AB  - The duct of the parotid gland had been indiscriminately named Stenon's duct or
      Stensen's duct. In order to establish its origin we carried out a biographic
      search and a brief revision of the life of the great anatomist, geologist,
      palaeontologist, bishop and finally Saint Nicolaus Stensen.

PMID- 15259849
TI  - [Respiratory orofacial and occlusion disorders associated with adenotonsillar
      hypertrophy].
AB  - AIM: Describe the effects of tonsil hyperplasia on the respiratory system,
      orofacial structures and the occlusion in children who present with it, showing
      the recognizable signs and symptoms for the dentist, the pediatrician and the
      otorhinolaryngologist to carry out an early diagnosis and proper treatment.
      MATERIAL AND METHOD: A bibliographical review of the topic has been performed by
      means of search in Medline, using as key words "tonsil hypertrophy" or "tonsil
      hyperplasia" and limiting the search to the last 10 years, studies in human
      beings and articles in English language whenever these included an abstract.
      RESULTS: The tonsil hyperplasia is the most frequent cause of the obstructive
      sleep apnea syndrome (OSAS) and snoring in children. These patients often present
      swallowing and speech problems, oral breathing, "adenoidal face", elongated and
      narrow face, small and triangular chin, mandibular retrognathia, highly-arched
      palate, decrease of the intermolar distance and protrusion of superior incisor
      teeth, with several types of dental malocclusion. CONCLUSIONS: It is very
      important to bear in mind that a multidisciplinary approach, specially amongst
      otorhinolaryngologists, pediatricians and dentists, is necessary for the
      diagnosis and treatment of a patient with adenotonsillar hyperplasia.

PMID- 15259850
TI  - [Maxillary fungal sinusitis by Zygomicetos. Report of a case in an
      immunocompetent patient].
AB  - We report the clinical case of a 36 years old female without significant previous
      history who was diagnosed with an acute maxillary sinusitis with not responding
      to antibiotic treatment. After her admission we asked for a CT which showed an
      occupation in the left maxillary sinus with a calcified area inside suggesting a
      mycetoma. The patient was operated by Functional Endoscopy Sinusal Surgery (FESS)
      plus Caldwell-Luc techniques sending the obtained sample for microbiological
      study, that was reported as sinusal mycosis by Zygomicetos. The postsurgical
      evolution was satisfactory.

PMID- 15259851
TI  - Direct determination of Pb(II) and Cd(II) ions as impurities in some homeopathic
      drugs by using stripping voltammetry.
AB  - The conditions for identification and quantilication of Pb(II) and Cd(II) ions as
      impurities in homeopathic preparations by stripping voltammetry were established.
      The tests proved that the method was of high selectivity. The detection limits
      were 0.78 ng/mL and 1.56 ng/mL for Pb(II) and Cd(II) ions, respectively. The
      method was characterised by: repeatability of measurements, a wide range of
      linearity and satisfactory percent recovery. The Pb(II) and Cd(II) ions were
      detected in examined drugs as impurities at concentrations of 1.23 ? 9.5 ng/mL
      and 1.66 ? 3.7 ng/mL for Pb(II) and Cd(II), accordingly.

PMID- 15259852
TI  - Application of UV-derivative spectra for determination of four
      antihyperlipidaemic drugs in pharmaceutical formulations.
AB  - A method for the determination of bezafibrate, ciprofibrate, fenofibrate and
      gemfibrozil in pharmaceutical formulations by first-, second- and third-
      derivative spectrophotometry is described, using "peak-peak" and "peak-zero"
      measurements. The calibration graphs were linear in the range 2-20 microg x mL(
      1) for all the compounds investigated. No interference was found from tablet
      excipients at the selected wavelengths and assay conditions. The developed
      methods were found to be validated and showed good precision and reproducibility
      (RSD = 1.57%, 0.78%, 1.45%, and 1.36%, respectively).

PMID- 15259853
TI  - The stability of 5-aminolevulinic acid and its ester derivatives.
AB  - Application of 5-aminolevulinic acid (ALA) and its esters for treatment of cancer
      and other disorders became a rapidly developing branch of photodynamic diagnosis
      and therapy. For clinical use, solutions of ALA (must be buffered to
      physiological pH. Unfortunately, in such conditions they are unstable. Two
      molecules of ALA condense and 2.5-(beta-carboxyethyl)-dihydropyrazine and 2.5
      (beta-carboxyethyl)-pyrazine are formed. Although, numerous eleborations relate
      to stability of ALA alone very little or none is known about the stability of
      ester derivatives of ALA. The present investigations have comprised the stability
      of ALA and its esters at 37 degrees C in respect of pH. concentration and time of
      reaction. The studies showed that ALA esters alike ALA undergo dimerisation at pH
      near 5. Moreover, it is possible that at pH>5.5 hydrolysis of the esters occurs,
      but this elaboration do not comprise explanation of this phenomenon.

PMID- 15259854
TI  - Dissolution behaviour of nalidixic acid solid dispersions using water soluble
      dispersion carriers.
AB  - The oral bioavailability of nalidixic acid (NA) is low due to its poor solubility
      and slow dissolution. Solid dispersions of NA containing varying concentrations
      of polyvinylpyrrolidone (PVP), beta-cyclodextrin (BCD) and sodium starch
      glycolate (SSG) were prepared by solvent evaporation technique in an attempt to
      improve dissolution rate of NA. Physical characterization of NA, physical
      mixtures (PM) and solid dispersions were investigated by a variety of analytical
      methods including scanning electron microscopy (SEM), infrared (IR) spectroscopy
      and powder X-ray diffraction (XRD). SEM was useful in the verification of
      possible nalidixic acid inclusion in the dispersion system by studying its
      surface and shape characteristics of different samples. IR analysis demonstrated
      no strong interaction between the drug and the carrier exists in the solid
      dispersions. The degree of crystallinity of nalidixic acid decreased and also
      differed with the dispersion systems of different carriers. Disolution studies
      indicated that the dissolution rate and percent dissolution efficiency (DE) were
      significantly increased in the solid dispersions compared with drug alone. The
      relative potency of the carriers to enhance the dissolution rate of nalidixic
      acid was in the order: BCD > PVP > SSG. The dissolution rate of the drug in the
      solid dispersions was faster when the ration of the drug to carrier was smaller.
      F-test suggests that first order model may be used for explaining the kinetics of
      drug release from all the solid dispersion systems.

PMID- 15259856
TI  - Influence of a novel platinum compound--cis-dichloro (dimethylsulphoxide) (1-beta
      D-rybofuranosyl-1,2,4-triazolo-3-arboxyamide) platinum (II)--"Pt-rib-1"--on cell
      cycle and apoptosis in ClS91 and B16 mouse melanoma in vitro.
AB  - Cisplatin has a significant role in the treatment of selected human tumors
      including advanced melanoma, but new platinum compounds are still in focus of
      search for better properties. Modern drug design is often based on studies
      detecting the abilities of tested drug to induce apoptosis and disturb cell
      cycle. Aim of the study was to establish the influence of a platinum complex Pt
      rib-1 on cell cycle and apoptosis occurrence in mouse melanoma B16 and ClS91
      cells. Pt-rib-1 is a ribavirin derivative. previously characterized and described
      as cytotoxic to B16 and ClS91 mouse melanoma cells in vitro. The new platinum
      complex (Pt-rib-1); cis- dichloro (dimethylsulphoxide) (1- beta- D-ribofuranosyl-
      1,2,4-triazolo -3- carboxyamide) platinum (II) was supplied.
      Cisdiaminodichloroplatinum (II), (cisplatin) was used in control groups. To
      detect apoptotic and necrotic cells, Annexin V- conjugated with fluorescein
      isothiocyanate (Annexin V-FITC, Immunotech) and propidium iodide (IP, Immunotech)
      were used. Apoptosis detection were done using fluorescence microscopy and flow
      cytometry. The total DNA content within the cell indicated phase of the cell
      cycle. DNA content was measured using flow cytometry. Values given represent the
      mean from three determinations. Results were presented as mean +/- standard
      deviation (SD). Statistical analysis was done using t-Student test. There were
      70.4% of apoptotic cells in the ClS91 culture after 24 h incubation with Pt-rib-1
      at a concentration of 2.04 x 10(-3) M (4 x IC50). In B16 group, 83.2 per cent of
      apoptotic cells was found after 24h incubation with Pt-rib-1 at high
      concentration (2.30 x 10(-3) M). A 24-h experiment shows a threshold at a
      concentration higher than 3 x IC50 responsible for apoptosis induction in B16 and
      ClS91 cells. After 48 h incubation with Pt-rib-1 the per cent of apoptotic cells
      increased gradually with rising concentrations of Pt-rib-1 up to a final
      concentration of 2.04 x 10(-3) M and 0.92 x 10(-3) M in ClS91 and B16 groups,
      respectively. Cell accumulation was observed in S phase after 48 h incubation
      with Pt-rib-1. The per cent of cells in S phase increased from 31 to 51.1% and
      38.8 to 50.0% in ClS91 and B16 culture, respectively. There were no B16 and ClS91
      cells in G2/M phase after incubation with higher concentrations of Pt-rib-1 (from
      0.2 to 2.0 x 10(-5) M/dm3). Pt-rib-1 partially exhibits action of cisplatin.
      which has no specific influence on cell cycle and ribavirin. probably responsible
      for DNA synthesis delay.

PMID- 15259855
TI  - Comparison of viability of B16 and Cl S91 cells in three cytotoxicity tests:
      cells counting, MTT and flow cytometry after cytostatic drug treatment.
AB  - In this study, results of three tests assessing viability of B16 and Cl S91 mouse
      melanoma cells after exposure to cytostatic drugs were compared: alive cell
      counting test after fixing with ethyl alcohol, MTT test and annexin V-FITC flow
      cytometry test. On the grounds of the obtained results the last mentioned method
      was recognized to be the most accurate and the least faulty. It was stated that
      mouse melanoma B16 cells are more sensitive to actinomycin D. cytosine
      arabinoside, cisplatin and dacarbazine than mouse melanoma Cl S91 cells. Mouse
      melanoma Cl S91 cells are more sensitive to vincristine than B16 cells.

PMID- 15259857
TI  - Synthesis and conformation analysis of 3-substituted derivatives of 1H,3H
      pyrido[2,3-d] pyrimidin-4-one of expected depressive nervous system. Part III.
AB  - Four series of new 1-aryl (heteroaryl) piperazinylacetyl derivatives of 1H,3H
      pyrido[2,3-d] pyrimidin-4-one VIIa-o were synthesised. Substrates for the
      synthesis of VIa-d were obtained from the respective 3H-pyrido[2.3-d]pyrimidines
      IVa-d in the reaction with NaBH4. Compounds VIa-d were prepared by
      chloroacetylation. The obtained 1-chloroacetyl derivatives in the reaction with
      respective aryl (heteroaryl) piperazine formed 1-aminoacetyl derivatives of 2
      phenyl-1 H.3H-pyrido[2.3-d]pyrimidin-4-one compounds VII1a-n. The structure ol
      compounds was analysed by 1H, 13C NMR spectroscopy.

PMID- 15259858
TI  - Synthesis of pyrido[2,1-c][1,2,4]triazine,1,2,4 triazolo[4,3-a] pyridine and 2
      (substituted-pyrazolyl)nicotinonitrile and their effect on Biomphalaria
      alexandrina snail enzymes.
AB  - The reaction of 2-hydrazino-4-(4-methoxyphenyl)-6-pheny-nicotinonitrile 3 with
      halo compounds yielded 4a-c,5,6. Heating 3 with carbon disulphide gave 7-(4
      methoxyphenyl)-5-phenyl-3-thioxo-2,3-dihydro [1,2,4-] triazolo [4,3-a] pyridine-8
      carboxylic amide 7. The behaviour of 3 towards some alpha,beta-unsaturated
      nitriles ,ethoxymethylene and ketene dithioacetal derivatives has been
      investigated, affording 9a-c,11a-c,13a-c,16a,b respectively. The activity of
      compounds 4a,5,6 and 7 have been investigated as molluscicidal.

PMID- 15259859
TI  - Flavonoids from flowers of Malva crispa L. (Malvaceae).
AB  - The following flavonoids were isolated and identified from the flowers of Malva
      crispa L.: kaempferol 3-O-beta-glucopyranoside, 3-O-(6"-tran-p-coumaroyl)-beta-D
      glucopyranoside, 7-O-beta-D-glucopyranoside, 3-O-alpha-L-rhamnopyranosyl (1-->6)
      beta-D-glucopyranoside and 3,7-O-diglucoside as well as quercetin 3-O-beta-D
      glucopyranoside, 3-O-alpha-L-rhamnopyranosyl (1-->6) -beta-D-glucopyranoside and
      apigenin 7-O-beta-D-glucopyranoside. Their structures were established by
      chemical analysis, UV, 1H and 13C NMR spectrometry.

PMID- 15259860
TI  - The quantitative determination of phenolic acids and antimicrobial activity of
      Symphoricarpos albus (L.) Blake.
AB  - The content of phenolic acids was determined in the extracts and fractions from
      leaves, flowers and fruits of Symphoricarpos albus (L.) Blake (Caprifoliaceae) by
      the Arnov's method. Antimicrobial activity of all extracts against Gram-positive
      anti Gram-negative microorganisms has been tested.

PMID- 15259862
TI  - Exploring effects of different antioxidants on dexamethasone-induced lipid
      peroxidation using common laboratory markers.
AB  - As a part of our ongoing effort to explore drug-induced lipid peroxidation in
      relation to drug-induced toxicity, our recent observations on lipid peroxidation
      induction potential of dexamethasone, a commonly used glucocorticoid compound in
      inflammatory and allergic conditions, has been presented considering lipid
      peroxidation a possible mediator of toxicity. An attempt was made to see the
      suppressive actions of some conventional antioxidant compounds, viz, ascorbic
      acid, alpha-tocopherol and probucol on dexamethasone-induced lipid peroxidation.
      It was found from the study that dexamethasone increased malondialdehyde content
      vis-a-vas decreased the level of reduced glutathione significantly in the liver
      homogenate. This suggests that dexamethasone caused a significant extent of lipid
      peroxidation which may be related to the toxic potential of the drug. It was
      further found all of the above antioxidants could suppress dexamethasone-induced
      lipid peroxidation to the significant extent.

PMID- 15259861
TI  - Effects of epsilon-aminocaproiloaminoacids on the amidolytic activity of tissue
      plasminogen activator, urokinase and kallikrein.
AB  - Effect of three epsilon-aminocaproylaminoacids with a significant
      antifibrinolytic activity on amidolytic activity of tissue plasminogen activator
      (t-PA), urokinase and kallikrein was examined. epsilon-Aminocaproyl-S-benzyl)-L
      cysteine and epsilon-aminocaproyl-L-norleucine were weak inhibitors of
      kallikrein. Weak activation of t-PA activity was observed at high concentration
      of the tested compounds. Only one of the examined dipeptides was a weak inhibitor
      of amidolytic activity of urokinase.

PMID- 15259863
TI  - Cerebral pathophysiology and critical care neurology: basic hemodynamic
      principles, cerebral perfusion, and intracranial pressure.
AB  - Pediatric neurologic intensive care differs from standard pediatric intensive
      care in two important respects. First, the diagnosis, monitoring, and management
      of problems related to disorders of cerebral perfusion and intracranial pressure
      (ICP) are central to nearly all of pediatric neurologic and neurosurgical
      intensive care. Second, various clinical problems normally encountered in the
      intensive care unit (ICU) have additional implications when associated with
      neurologic disease. Regardless of the cause, treatment should be undertaken as
      expeditiously as possible and should be based on the principles of resuscitation,
      reducing the volume of the intracranial contents, and reassessment. This chapter
      aims to outline some basic principles underlying the diagnosis and management of
      elevated ICP in children.

PMID- 15259864
TI  - Evaluation of coma and brain death.
AB  - Coma is a nonspecific sign of widespread central nervous system impairment
      resulting from various metabolic and structural etiologies. The rapid recognition
      of this neurologic emergency and results from the history, physical examination,
      and early investigative studies are key to the identification and treatment of
      its underlying cause. The prognosis for recovery depends greatly on the
      underlying etiology as well as on its optimal treatment, which seeks to preserve
      neurologic function and maximize the potential for recovery by reversing the
      primary cause of brain injury, if known, and preventing secondary brain injury
      from anoxia, ischemia, hypoglycemia, cerebral edema, seizures, infections, and
      electrolyte and temperature disturbances. Brain death must be diagnosed with
      similar care and precision, and families approached compassionately about the
      diagnosis and their decisions regarding organ donation.

PMID- 15259865
TI  - Neonatal intensive care neurology.
AB  - The pediatric neurologist's role in the neonatal intensive care unit is described
      in four clinical settings: (1) assessment of outcome in neonatal encephalopathy,
      (2) treatment of seizures in full-term infants, (3) assessment and treatment of
      intraventricular hemorrhage with posthemorrhagic hydrocephalus, and (4)
      assessment of outcome in preterm infants. Emphasis is placed on the evidenced
      based information available in these settings and on new therapies on the
      horizon. Using evidence-based information, the pediatric neurologist can
      accurately assess prognosis in the neonatal period, and this can provide the
      basis for a rational assessment of newer therapies in neonatal intensive care.

PMID- 15259866
TI  - The treatment of status epilepticus.
AB  - Status epilepticus (SE) is a life-threatening emergency that requires prompt
      treatment, including basic neuroresuscitation principles (the ABCs),
      antiepileptic drugs to stop the seizure, and identification of etiology.
      Symptomatic SE is more common in younger children. Treating the precipitating
      cause may prevent ongoing neurologic injury and facilitates seizure control. A
      systematic treatment regimen, planned in advance, is needed, including one for
      refractory status epilepticus (RSE). Here we emphasize definitions, clinical and
      electroencephalography stages, early treatment, special circumstances that may
      require immediate seizure control, and treatment of RSE. Because much clinical
      research in SE has been done in adults, we indicate the patient population
      studied.

PMID- 15259867
TI  - Cerebrovascular disorders.
AB  - Arterial ischemic stroke is being recognized more commonly in the pediatric
      population. The etiologies differ greatly from those seen in adults. The most
      common etiologies are congenital heart disease and sickle cell disease. Children
      may present with or without hemiparesis and may have fever, headache, and
      depressed level of consciousness. A high index of suspicion is needed to diagnose
      stroke. Although clinical studies are scarce in children, besides early
      diagnosis, early specialized care with careful attention to detail ensuring
      adequate oxygenation and ventilation, prevention of hyperthermia and seizures,
      and maintenance of blood pressure and metabolic balance are important and likely
      improve outcome in these children. Selective children may also benefit from
      anticoagulant therapy, and, as the interval to diagnosis decreases, thrombolytic
      therapy may become an option although safety data are required. Children with
      acute stroke should be rapidly transported to and cared for in a pediatric center
      with a specialized stroke team or access to acute stroke protocols.

PMID- 15259868
TI  - Neuromuscular problems of the critically ill neonate and child.
AB  - This review presents insights gained over 24 years of clinical and laboratory
      evaluations of children, newborn to 18 years of age, who present with acute
      weakness in the intensive care setting. The differential diagnosis of
      neuromuscular disorders in these cases begins with recognition of three
      categories-the infant and toddler, the older child and adolescent, and the child
      with critical illness-within which predisposition to specific disorders may be
      identified. Disorders originating from anterior horn cell, peripheral nerve,
      neuromuscular junction, and muscle cell are discussed with emphasis on
      presentation and electrophysiologic findings. Nerve conduction studies,
      electromyography, electroencephalography, cerebrospinal fluid analysis, and
      magnetic resonance imaging each play important diagnostic roles in the
      differentiation of neuromuscular disorders in the critically ill child. Case
      studies suggest the wide range of presentations these disorders may make to the
      pediatrician or pediatric neurologist.

PMID- 15259869
TI  - Neurosurgical aspects of critical care neurology.
AB  - The management of the pediatric neurosurgical patient requires a detailed
      understanding of the diagnosis and management of disorders of ICP. Frequently the
      care of these patients will require collaboration between several different teams
      of physicians. Most important, frequent and clear communication between the ICU
      physician and the neurosurgeon will facilitate the delivery of the best-quality
      care to these children. This chapter will identify and discuss issues relevant to
      neurosurgeons and intensive care physicians taking care of children with complex
      problems related increased intracranial pressure.

PMID- 15259870
TI  - Ethical issues in pediatric critical care neurology.
AB  - Ethical issues in the critical care unit frequently arise in children with
      neurological problems. These ethical issues frequently challenge our medical
      management of such cases and can be quite problematic. This article reviews key
      ethical issues that may arise including informed consent, futility,
      justice/rationing, clinical research conduct and the severely compromised patient
      who is in either a permanent vegetative or minimally conscious state.

PMID- 15259871
TI  - Novelty seeking in adulthood: increases accompany decline.
AB  - Using stereotypes, researchers have predicted that novelty seeking declines in
      adulthood. Through this cross-sectional study, the authors revealed that only the
      external sensational type of novelty seeking declined, whereas the internal
      sensational and internal and external cognitive types remained stable or
      increased. A population of 233 adults (152 men, 81 women) completed the Novelty
      Experiencing Scale (P. H. Pearson, 1970). Correlational analyses revealed that
      older men sought novelty more frequently through cognition than did younger men
      and that older women were less likely than were younger women to seek novelty
      through their senses. Multivariate analysis of variance, 2 x 5 (Gender x Age),
      showed that cognitive novelty seeking increased significantly among participants
      younger than 50 years of age. Sensational novelty seeking was lower among women
      older than 40 years and among men older than 50 years. The analyses revealed no
      significant Gender x Age interactions.

PMID- 15259872
TI  - Environmental and individual influences on Australian young adults' likelihood of
      attending university: a follow-up study.
AB  - In this longitudinal study, which is a follow-up analysis of a previous
      investigation (K. Marjoribanks, 2002a), the author examined environmental and
      individual influences on the likelihood of Australian young adults attending
      university. Participants were 5,181 Anglo-Australian (parents born in Australia,
      English was the language of the family), 460 Asian, 699 English (parents born in
      England), 746 European, and 163 Middle Eastern students (M age = 14.7 years, when
      the study began). The analyses indicated that Asian, European, and Middle Eastern
      young adults were more likely to attend university than were young adults from
      Anglo-Australian and English families, and young women had higher odds of
      attending university than did young men. Family social status variations in the
      likelihood of university attendance could be explained by differences in
      individual characteristics and proximal learning environments. Adolescents'
      individual characteristics and proximal learning environments combined to have a
      large independent association with the decision to attend university.

PMID- 15259873
TI  - Did Columbus hypothesize or predict that if he sailed due west, he would arrive
      at the Indies?
AB  - A review of the literature in science education shows that most students have
      difficulties in hypothetico-deductive reasoning. The author's objective in this
      study was to investigate the abilities of high school teachers and university
      teachers to understand the difference between the terms hypothesis and prediction
      in the everyday context of Columbus's discovery of America. The author asked 83
      high school and university teachers enrolled in a methodology course to elaborate
      and to explain a prediction and a hypothesis based on Columbus's discovery.
      Results, based on written responses, showed that most teachers (approximately
      60%) did not understand the difference between a hypothesis and a prediction. The
      author also observed that many teachers did provide a satisfactory description of
      what they considered to be a hypothesis and a prediction. However, the difficulty
      for the teachers consisted in operationalizing (elaborating and understanding)
      the difference between a hypothesis and a prediction. Some teachers explicitly
      elaborated and classified a prediction as a hypothesis and, at times, the
      teachers elaborated the two terms in the same manner, without being aware of the
      contradiction. The study has educational implications by showing that, just like
      students, teachers have difficulties with the elaboration and understanding of
      the concepts of hypothesis and prediction. Given the importance of such concepts
      for all research programs, it is essential that appropriate teaching strategies
      be implemented.

PMID- 15259874
TI  - Assisted reproduction versus spontaneous conception: a comparison of the
      developmental outcomes in twins.
AB  - The use of assisted reproductive technology is increasing rapidly. Research,
      although sparse, has resulted in inconsistent findings as to the developmental
      prognosis for infants conceived by assisted reproductive techniques such as in
      vitro fertilization and the use of fertility drugs. In the present study, the
      authors compared twins who were spontaneously conceived with those who were
      conceived through assisted reproductive technology. The authors found differences
      in birth weight and gestational age. Infants conceived by assisted reproductive
      technology fared worse than did those who were spontaneously conceived. The
      authors found no differences between the groups in mental development at 24
      months of age, but they found evidence of differences in physical development.
      Implications of the findings are discussed.

PMID- 15259875
TI  - Challenging behaviors in young children: the father's role.
AB  - In this study, the authors examined the parenting practices, developmental
      expectations, and stress levels of 136 fathers and the challenging and prosocial
      behaviors of their 1- to 5-year-old children. In addition, the authors
      systematically addressed fathers' qualitative concerns about their parenting. The
      authors divided the participants into 4 groups and controlled for family
      socioeconomic status (SES) and the focus child's gender. Results showed a
      significantly higher use of corporal and verbal punishment and parenting stress
      among lower income fathers. Secondary analyses demonstrated a significant effect
      of paternal disciplinary practices that emphasized the frequent use of corporal
      and verbal punishment on child behavior problems, regardless of SES level. On a
      positive note, fathers from both lower and higher SES groups had reasonable
      developmental expectations for their boys and girls, and they reported similar
      frequencies of their children's prosocial behavior. The authors discuss the need
      for early parent education programs that include fathers and that teach specific
      strategies to address child behavior problems.

PMID- 15259876
TI  - Correlates of aggression in African American and Puerto Rican children.
AB  - The authors examined a cross-sectional interrelationship of psychosocial domains
      as they relate to aggression in a group of African American and English-speaking
      Puerto Rican children living in New York City. The population included 80
      biological children of African American and Puerto Rican young adults who had
      been participating in the authors' ongoing longitudinal study, and 77 mothers or
      mother substitutes (rearing mothers) of those children. The authors performed
      hierarchical multiple regression analysis. The results indicated that (a) the
      child's personality and maternal attributes were significantly related to the
      child's aggression, despite control on all of the other domains and (b) the
      ethnic identification and discrimination domain was no longer related to the
      child's aggression with control on the mother-child relationship domain or on the
      child's personality domain. The findings have implications for clinical practice
      and public policy.

PMID- 15259877
TI  - Illicit drug use and risky sexual behavior among African American and Puerto
      Rican urban adolescents: the longitudinal links.
AB  - The authors assessed whether (a) early illicit drug use predicted later risky
      sexual activity, (b) early risky sex predicted later illicit drug use, and (c)
      common factors affected both risky sexual behavior and illicit drug use. African
      American and Puerto Rican youth completed questionnaires in their classrooms at
      Time 1 (T1) and face-to-face interviews with the authors in their homes 5 years
      later at Time 2 (T2). Logistic regression analyses showed the association between
      T1 illicit drug use and T2 risky sexual activity and between T1 risky sexual
      behavior and T2 illicit drug use. With few exceptions, T1 illicit drug use was
      associated with all of the T2 risky sexual behaviors. After controlling for
      demographic factors, the authors found that multiple sex partners at T1 was not
      related to illicit drug use at T2. Condom use at T1 was related to illicit drug
      use at T2, whereas sexually transmitted diseases and adolescent pregnancy were
      not related to this drug use. The findings indicated that assessments of and
      treatments for substance use should focus on the risky sexual behaviors that seem
      to accompany illicit drug use.

PMID- 15259878
TI  - Changing investment in activities and interests in elders' lives: theory and
      measurement.
AB  - Socioemotional selectivity and gerotranscendence, newer theories with roots in
      the disengagement theory of aging, provided the theoretical framework for a new
      measure of perceived change in investment in a variety of pursuits. The 30-item
      Change in Activity and Interest Index (CAII) was given to a sample of 327
      outpatients aged 65-94. Items with at least 30% decreased investment responses
      included Entertaining in my home, Concern with others' opinions, Shopping and
      buying things, and Attending social events with new people. Principal Components
      Analysis of the index with dichotomous recoding (less vs. more or same
      investment) resulted in four factors: Active Instrumental (AI), Social
      Intellectual (SI), Spiritual Concerns (SC), and Transcendence (TR). Support for
      socioemotional selectivity and gerotranscendence is evident in the reported
      increase of importance of SI pursuits, with concurrent decrease in importance of
      AI activities among these respondents. Zero-order correlations of component
      scores with study variables suggest that AI and SI are more clearly related to
      older age, functional impairment, and negative affect than are SC and TR. The
      CAII appears to tap several dimensions of change in interests; the index gives
      geriatric mental health practitioners and researchers a tool to measure an aspect
      of social development that has been neglected in gerontology.

PMID- 15259879
TI  - Age-related health stereotypes and illusory correlation.
AB  - This experiment investigated how age-related health stereotypes affect people's
      judgments of younger and older patients' medical compliance. Previous research
      has shown that stereotypes of young adults include healthy components, but
      stereotypes of older adults include both healthy and unhealthy components
      (Hummert, 1990). We predicted that younger patients in poor health would violate
      people's expectations about health in younger individuals. As a result of this
      violation, people would perceive younger patients to be more non-cooperative than
      older patients. On the other hand, because people's stereotypes of older patients
      contain both good and poor health components, non-cooperative older patients
      would be no more memorable than cooperative older patients. These hypotheses were
      supported by data showing that both younger and older participants formed
      illusory correlations between younger patients and non-cooperative behavior, but
      not between older patients and non-cooperative behavior. Implications for how age
      related health stereotypes might affect beliefs about compliance and healthcare
      policy are discussed.

PMID- 15259880
TI  - Revisiting the generation gap: exploring the relationships of parent/adult-child
      dyads.
AB  - There is some evidence that older parents and their adult children may evaluate
      their relationships with each other in different ways. To date, we know little
      about what may account for these discrepancies. This investigation compares the
      perceptions of intergenerational solidarity among 2,590 adult-child/older-parent
      dyads from the National Survey of Families and Households. Further, this study
      examines a social structural model to test the relative contribution of
      individuals' sociodemographic and social structural positions to the
      correspondence between generational perceptions of solidarity. The findings
      indicate that there is a high degree of disagreement between how adult children
      and their parents view their relationship. Parents are more likely to report
      greater relationship quality, while children report greater contact and exchanges
      of assistance. While a number of variables influence the correspondence between
      generations, the strongest and most consistent predictors are sex, age, child's
      marital status, and residential proximity.

PMID- 15259881
TI  - Personal experience of aging in the children of a parent with dementia.
AB  - We investigated whether adults with a parent with dementia experience their
      personal aging differently than adults whose parents do not have dementia. Semi
      structured interviews were conducted with 25 adults who had a parent with
      dementia and 25 controls. We found that, although in a general sense the two
      groups were quite similar in their personal experiences of aging, there were
      specific differences. The children of parents with dementia had a health-concept
      in which there was substantial emphasis on mental health. Moreover, they linked
      the dementia of their parent to their own aging and worried about developing a
      dementia syndrome themselves. They also held different attitudes with regard to
      end-of-life decisions. Finally, participants having a parent with dementia gave
      more extensive answers to simple questions. This overall response suggests more
      involvement with growing older and finitude in the children of parents with
      dementia.

PMID- 15259882
TI  - A comparison of collaborative and individual everyday problem solving in younger
      and older adults.
AB  - To understand the conditions under which age differences in everyday problem
      solving performance occur, this study investigated individual and collaborative
      problem solving. Younger (24 females, 24 males; M age = 19.98, SD = 1.43) and
      older adults (25 females, 24 males; M age = 71.14, SD = 6.65) worked either alone
      or with a same-sex friend to plan a cross-country trip to attend a wedding. Age
      differences favoring younger adults were found on three of eight performance
      measures: two component completion accuracy variables (i.e., city completion, Mt.
      Rushmore completion) and a composite variable that assessed overall performance.
      Younger adults also completed the task faster than did older adults.
      Collaborators out-performed individuals on the composite measure of overall
      performance and frequency of planning errors. Females committed more planning
      errors than males did. Younger and older adults' performances were predicted by
      different variables; however, basic abilities were not consistently significant
      predictors of performance for either younger or older adults. The results of the
      study suggest that task characteristics may differentially influence older and
      younger adults' collaborative performance.

PMID- 15259883
TI  - Older persons' perceptions of the frequency and meaning of elderspeak from
      family, friends, and service workers.
AB  - Older persons (N = 159) were surveyed for their impressions of and experiences
      with elderspeak from friends, same-age family members, younger family members,
      familiar service workers, and unfamiliar service workers. Two dimensions,
      "warmth" and "superiority," emerged in the judgments of elderspeak from all five
      speaker types. Respondents perceived more warmth and less superiority in
      elderspeak from friends than they did in elderspeak from unfamiliar service
      workers. Among younger seniors, elderspeak was received primarily from unfamiliar
      service workers, whereas among nursing home residents, elderspeak was received
      from all speaker types. Variation thus exists in the covert experiences of
      elderspeak from different sources, and in the frequency of receipt of elderspeak
      from different sources.

PMID- 15259884
TI  - Beyond money and survival: the meaning of paid work among older women.
AB  - This article explores the meaning and experiences of paid work for older women.
      Taped, in-person interviews were conducted with 53 ethnically and economically
      diverse women, 55 to 84 years old. The interview guide contained open-ended
      questions regarding the meaning of work, reasons for working, and the centrality
      of work to personal identity. Participants discussed the following topics:
      independence from men; lost dreams and regrets related to paid work and
      educational opportunities; being responded to as mother by co-workers and
      supervisors; and working above and beyond the call of duty.

PMID- 15259885
TI  - The effects of emotional content and aging on false memories.
AB  - After studying a list of words related to a nonpresented lure word, people often
      falsely recall or recognize the nonpresented lure. Older adults are particularly
      susceptible to these forms of false memories. The age-related false memory
      enhancement likely occurs because older adults do not encode, or later retrieve,
      items in enough detail to allow them to discriminate between presented words and
      other associated but nonpresented items. Pesta, Murphy, and Sanders (2001)
      suggested that the emotional salience of the lures may provide distinctiveness,
      so that individuals would be less likely to endorse an emotional lure as a
      studied item than to endorse a neutral lure. In the present investigation, young
      and older adults were less likely to falsely recall or recognize emotional, as
      compared with neutral, lures. Both age groups appeared capable of using the
      distinctiveness of the emotional lures to reduce, although not to eliminate,
      false recall and recognition.

PMID- 15259886
TI  - Dissociating semantic and phonological maintenance using fMRI.
AB  - Functional magnetic resonance imaging (fMRI) distinguished regions of neural
      activity associated with active maintenance of semantic and phonological
      information. Subjects saw a single word for 2 sec, and following a 10-sec delay,
      made a judgment about that word. In the semantic task, subjects focused on the
      meaning of the word and decided whether a second word was synonymous with it. In
      the phonological task, subjects repeated the word silently and decided whether it
      shared a vowel sound with a nonsense word. Analyses allowed for isolation of
      neural activity during the maintenance delay. Semantic maintenance elicited
      greater activity in bilateral inferior frontal gyrus and left middle temporal
      gyrus regions of interest (ROI). In contrast, there was greater activity for
      phonological maintenance in the left superior parietal ROI. These results show a
      frontal-temporal network involved in actively maintaining the meanings of words,
      and they indicate that semantic and phonological maintenance processes are
      dissociable within working memory.

PMID- 15259887
TI  - When does word meaning affect immediate serial recall in semantic dementia?
AB  - Patients with semantic dementia can show superior immediate recall of words that
      they still understand relatively well, as compared with more semantically
      degraded words, suggesting that conceptual knowledge makes a major contribution
      to phonological short-term memory. However, a number of studies have failed to
      show such a recall difference, challenging this view. We examined the effect of
      several methodological factors on the recall of known and degraded words in 4
      patients with semantic dementia, in order to investigate possible reasons for
      this discrepancy. In general, our patients did exhibit poorer recall of the
      degraded words and made more phonological errors on these items. In addition, set
      size affected the magnitude of the recall advantage for known words. This finding
      suggests that semantic degradation influenced the rate of learning in the
      immediate recall task when the same items were presented repeatedly. The methods
      used to select known and degraded items also impacted on the recall difference.
      List length, however, did not affect the advantage for known words. The coherence
      of items in phonological short-term memory was affected by their semantic status,
      but not by the length of the material to be retained. The implications of these
      findings for the role of semantic and phonological representations in verbal
      short-term memory are discussed.

PMID- 15259888
TI  - Effect of name agreement on prefrontal activity during overt and covert picture
      naming.
AB  - In recent neuroimaging studies, various tasks have been used to examine
      prefrontal cortex involvement in semantic retrieval and selection. One such task,
      picture naming, has yielded inconsistent results across studies. One potential
      explanation for this inconsistency is that the magnitude of prefrontal activity
      during picture naming depends on the extent to which a given picture evokes a
      single reliable meaning. To test this hypothesis, fMRI activity in the prefrontal
      cortex was measured while subjects named pictures with either high or low name
      agreement. In Experiment 1, subjects named black-and-white line drawings, either
      covertly or overtly. Across both modalities, we found more left inferior frontal
      gyrus (LIFG) activity when the subjects named low-agreement pictures than when
      they named high-agreement pictures. No significant difference in head movement
      was detected between the two modalities. In Experiment 2, we replicated the
      effect of name agreement on LIFG activity during picture naming, using black-and
      white photographs. These results provide further support for the idea that the
      LIFG mediates selection among competing alternatives and suggest a means for
      understanding the naming deficits observed in nonfluent aphasia.

PMID- 15259889
TI  - Recall and recognition are equally impaired in patients with selective
      hippocampal damage.
AB  - In two recent studies, the hypothesis that recall is more severely impaired than
      recognition in patients with damage thought to be limited to the hippocampus was
      tested. Yonelinas et al. (2002) reported findings that appeared to support this
      hypothesis, whereas Manns, Hopkins, Reed, Kitchener, and Squire (2003) found that
      recall and recognition were equally impaired. An analysis of the individual
      subject data from the two studies revealed that the apparent disagreement stemmed
      from the inclusion of a single outlying recognition score for 1 of the 55 control
      subjects in Yonelinas et al. (2002). When that outlier was excluded, the studies
      were in agreement that recognition and recall are substantially and similarly
      impaired in these patients. Yonelinas et al. (2002) also analyzed remember/know
      judgments and ROC data in an effort to show that recollection is selectively
      impaired in patients, but these analyses also raise problems.

PMID- 15259890
TI  - The neurobiology of adaptive learning in reading: a contrast of different
      training conditions.
AB  - fMRI was used to investigate the separate influences of orthographic,
      phonological, and semantic processing on the ability to learn new words and the
      cortical circuitry recruited to subsequently read those words. In a behavioral
      session, subjects acquired familiarity for three sets of pseudowords, attending
      to orthographic, phonological, or (learned) semantic features. Transfer effects
      were measured in an event-related fMRI session as the subjects named trained
      pseudowords, untrained pseudowords, and real words. Behaviorally, phonological
      and semantic training resulted in better learning than did orthographic training.
      Neurobiologically, orthographic training did not modulate activation in the main
      reading regions. Phonological and semantic training yielded equivalent behavioral
      facilitation but distinct functional activation patterns, suggesting that the
      learning resulting from these two training conditions was driven by different
      underlying processes. The findings indicate that the putative ventral visual word
      form area is sensitive to the phonological structure of words, with
      phonologically analytic processing contributing to the specialization of this
      region.

PMID- 15259891
TI  - Contributions of the human pulvinar to linking vision and action.
AB  - In 3 patients with unilateral pulvinar lesions, we tested the pulvinar's role in
      selective attention processing. Each patient completed four variants of a flanker
      interference task in which they reported the color of a square of a specified
      size while ignoring an irrelevant flanker that appeared either contralesionally
      or ipsilesionally to the target. The main finding was that when target location
      was not known and target and flanker were associated with competing responses,
      reaction times to contralesional targets were longer than those to ipsilesional
      targets. Our findings suggest that pulvinar damage produces a contralesional
      deficit in response competition.

PMID- 15259893
TI  - The influence of protease inhibitor resistance profiles on selection of HIV
      therapy in treatment-naive patients.
AB  - Although protease inhibitors (PIs) have dramatically improved outcomes in HIV
      infected patients, half still fail treatment with PI-based combination therapy.
      Genetic pressure from incomplete viral suppression rapidly selects for HIV
      variants with protease gene mutations that confer reduced susceptibility to PI
      drugs. A number of specific amino acid substitutions have been associated with PI
      resistance. However, high-level resistance to individual PIs requires the
      accumulation of several primary and secondary mutations, developing along drug
      specific, step-wise pathways. HIV variants resistant to saquinavir and ritonavir
      usually contain L90M and V82A substitutions, respectively. Indinavir resistance
      may be linked to substitutions at positions 46 or 82. Resistance to nelfinavir is
      primarily associated with D30N but may alternatively be found with L90M.
      Resistance during exposure to amprenavir can follow development of I50V, which
      also may confer resistance to lopinavir. Failure during treatment with atazanavir
      is closely linked to 150L. The overlapping of these pathways can lead to multiple
      PI resistance, limiting therapeutic options in antiretroviral-experienced
      patients. Reduced susceptibility to more than one PI is most likely to be
      associated with amino acid substitutions at six positions: 10, 46, 54, 82, 84 and
      90. Other mutations (D30N, G48V, I50V or I50L) are relatively specific for
      particular PIs and are less likely to produce cross resistance. Certain
      resistance mutations selected by exposure to one PI may actually increase
      susceptibility to others. Patients newly diagnosed with HIV infection are
      increasingly found to harbour virus that is resistant to the more commonly used
      drugs. Newer PIs may select for mutations that result in less cross resistance
      with older agents.

PMID- 15259892
TI  - Laterality effects in the recognition of depth-rotated novel objects.
AB  - The dissociable neural subsystems theory proposes that left-hemisphere (LH)
      performance is dominated by a viewpoint-invariant (VI) recognition subsystem,
      whereas right-hemisphere (RH) performance is dominated by a viewpoint-dependent
      (VD) subsystem (Marsolek, 1999). Studies supporting this theory have used
      familiar objects and, therefore, may have been confounded by characteristics
      beyond perceptual features. Experiment 1, a lateralized sequential-matching task
      with novel objects, showed VD recognition in both hemispheres. In Experiment 2,
      some participants learned semantic associations for four novel objects, whereas
      others were exposed to the novel objects without the semantic associations. Both
      groups later performed a depth-rotated lateralized sequential-matching task. The
      participants who had learned semantic associations showed greater VD performance
      in the RH than in the LH; however, the participants in the control group showed
      equivalent VD performance in both hemispheres. The results suggest that
      hemispheric differences in VD performance may be partially attributable to an LH
      advantage for semantic processing.

PMID- 15259894
TI  - Genotypic determinants of the virological response to tenofovir disoproxil
      fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.
AB  - OBJECTIVE: To assess the genotypic determinants of the virological response to
      tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral
      (ARV)-experienced patients receiving TDF as a part of a salvage therapy. METHODS:
      HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the
      French expanded access program receiving a stable TDF-including regimen for 3
      months or more. Reverse transcriptase mutations associated with the viral load
      decrease at month 3 with a P-value <0.15 were retained for the construction of a
      mutation score. The score was then validated using a multivariate analysis and
      bootstrap resampling method. RESULTS: The strongest association with decrease in
      viral load was observed with a set of seven mutations (TDF mutation score) that
      consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations.
      The RT K65R mutation and the insertions at codon 69 were not included in the
      analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the
      absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF
      with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7
      log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the
      decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered
      possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6,
      previous use of amprenavir, indinavir and lopinavir, and co-prescription of
      didanosine were associated with a worse virological response. The bootstrap
      analysis showed the robustness of the TDF mutation score. CONCLUSION: In ARV
      experienced patients receiving TDF-containing regimens, a score derived from
      seven reverse transcriptase mutations was shown to be independently predictive of
      the virological response.

PMID- 15259895
TI  - Interferon-lamivudine combination is no better than lamivudine alone in anti-HBe
      positive chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Results of studies using lamivudine and interferon
      combination in the treatment of chronic hepatitis B are not consistent or
      conclusive. This study aimed to evaluate the efficacy of interferon plus
      lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B.
      METHODS: Eighty patients were treated with either lamivudine or lamivudine plus
      simultaneously started interferon. Patients were assigned in groups according to
      random allocation rule. Lamivudine was given 150 mg/day for 96 weeks in each
      group; interferon was administered 10 MU three times a week for 24 weeks in the
      combination therapy group. RESULTS: Alanine aminotransferase (ALT) normalization
      was achieved earlier in patients treated with lamivudine alone. At the end of
      treatment, there was no difference between the groups with respect to HBV DNA
      negativity, ALT normalization and breakthrough rate. Histological improvement was
      remarkable in each group, but fibrosis score and necro-inflammatory activity were
      much lower in lamivudine-treated patients. CONCLUSIONS: Addition of interferon to
      the lamivudine regimen does not increase the effectiveness of the treatment.
      Considering the side effects of interferon treatment, this combination seems not
      to be convenient for anti-HBe-positive chronic hepatitis B.

PMID- 15259896
TI  - Safety and efficacy of once-daily didanosine, tenofovir and nevirapine as a
      simplification antiretroviral approach.
AB  - OBJECTIVE: To assess the efficacy and safety of a once-daily antiretroviral
      regimen in HAART-experienced subjects with long-lasting viral suppression.
      METHODS: One-hundred-and-sixty-nine patients with chronically suppressed viral
      load (limit of detection <50 copies/ml) were recruited. Based on patient
      willingness to simplify treatment, 84 of them continued receiving their usual
      treatment (BID Group) and 85 switched to once-daily
      didanosine/tenofovir/nevirapine (QD Group) in a non-randomized fashion. RESULTS:
      At week 48, the proportion of patients with viral suppression in the QD and in
      the BID Group, respectively, was 97 vs 100% in the per-protocol analysis (P =
      0.497), and 76 vs 86% for the intention-to-treat analysis (P = 0.176).
      Nevertheless, CD4 count decreased in the QD Group, with a mean decline of 95
      cells/mm3 (95% CI: 45-145). Twelve subjects in the QD Group (14%) discontinued
      treatment due to adverse events, mainly nevirapine-related hepatitis (6%). No
      significant differences regarding the rate of acute pancreatitis or peripheral
      neuropathy were observed between both groups. A significant improvement in the
      lipid profile was only seen in the QD Group. High levels of adherence were
      observed in both groups during follow-up, as well as a good quality of life. At
      week 48, a reduction in effort to take medication (P < or = 0.001) and an
      increment in the satisfaction with the treatment (P < 0.001) was only seen in the
      QD group. No differences were observed in median nevirapine trough levels between
      patients on twice-daily nevirapine at baseline (4820 ng/ml) and subjects in the
      QD Group (6090 ng/ml, P = 0.30). CONCLUSION: Treatment simplification to a once
      daily antiretroviral regimen based on didanosine, tenofovir and nevirapine may be
      a valid approach in HIV-infected subjects with long-lasting viral suppression.
      Combination of standard doses of didanosine and tenofovir may have contributed to
      the CD4 cell decline observed with this QD regimen.

PMID- 15259897
TI  - Simple linear model provides highly accurate genotypic predictions of HIV-1 drug
      resistance.
AB  - Drug resistance is a major obstacle to the successful treatment of HIV-1
      infection. Genotypic assays are used widely to provide indirect evidence of drug
      resistance, but the performance of these assays has been mixed. We used standard
      stepwise linear regression to construct drug resistance models for seven protease
      inhibitors and 10 reverse transcriptase inhibitors using data obtained from the
      Stanford HIV drug resistance database. We evaluated these models by hold-one-out
      experiments and by tests on an independent dataset. Our linear model outperformed
      other publicly available genotypic interpretation algorithms, including decision
      tree, support vector machine and four rules-based algorithms (HIVdb, VGI, ANRS
      and Rega) under both tests. Interestingly, our model did well despite the absence
      of any terms for interactions between different residues in protease or reverse
      transcriptase. The resulting linear models are easy to understand and can
      potentially assist in choosing combination therapy regimens.

PMID- 15259898
TI  - In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and
      tenofovir.
AB  - Emergence of lamivudine-resistant hepatitis B virus (HBV) is a major concern in
      human immunodeficiency virus (HIV) and HBV coinfected patients. Following
      selection of resistant mutants, hepatitis flare or rapid progression to cirrhosis
      may occur. Treatment of patients with new nucleotide analogues such as adefovir
      dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF) has shown good efficacy in
      controlling wild-type or lamivudine-resistant HBV replication. The purpose of
      this study was to assess the in vitro efficacy of new nucleotide analogues on HBV
      strains isolated from lamivudine-treated patients. After purification of HBV DNA
      from patient sera, the whole HBV genome was PCR-amplified and cloned. Drug
      sensitivity was measured after transfection of the isolated full genomes into
      HepG2 cells and measurement of HBeAg, HBsAg and viral replication in the culture
      media under increasing drug concentrations. A wild-type strain isolated from an
      untreated patient served as control. In a clinical study of ADV (Gilead 460i
      study), seven of the 35 patients carried HBV strains with the triple lamivudine
      resistance-associated amino-acid changes rtV173L/L180M/M204V at baseline.
      Although all patients responded to ADV in this clinical study, the serum HBV
      reduction was lower in the seven patients with the triple mutation (median -3.3
      log copies/ml) compared to the patients who had only the rtL180M/M204V mutations
      (median -4.1 log copies/ml) at week 48 (P=0.04, Mann-Whitney test). In our in
      vitro system, lamivudine IC50 on lamivudine-resistant HBV carrying amino-acid
      substitutions rtL180M and rtM204V within the polymerase encoding region increased
      by more than 16,000-fold (from 6 nM to over 100 microM) when compared to wild
      type HBV. For ADV and TDF, comparison of wild-type and lamivudine-resistant HBV
      IC50 (rtL180M-M204V) showed, respectively, 2.85-fold (from 0.07 to 0.2 microM)
      and 3.3-fold (from 0.06 to 0.2 microM) increases, indicating a mild decrease of
      both drug activities, in vitro. At the ADV concentration of 0.1 microM, presence
      of the V173L mutation reduced the inhibition of HBsAg production from 50 to 30%
      (P<0.01) and the viral replication from 45 to 32% (P<0.01, Mann-Whitney).
      Conversely, tenofovir had similar potency on both HBV mutation profiles with 60%
      inhibition of HBsAg production and 45% inhibition of viral replication at 0.1
      microM. Our study supports the high efficacy of ADV and TDF seen in patients
      after lamivudine breakthrough. The excellent activity of TDF on lamivudine
      resistant virus independently of the resistance mutation profile offers an
      interesting treatment alternative to HIV-HBV coinfected patients.

PMID- 15259899
TI  - Prophylactic and therapeutic effects of small interfering RNA targeting SARS
      coronavirus.
AB  - OBJECTIVES: To identify and characterize the siRNA duplexes that are effective
      for inhibition of SARS-CoV infection and replication in the non-human primate
      cells. This in vitro study will serve as the foundation for development of novel
      anti-SARS therapeutics. METHODS: 48 siRNA sequences were designed for targeting
      regions throughout entire SARS-CoV genome RNA including open-reading frames for
      several key proteins. Chemically synthesized siRNA duplexes were transfected into
      foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The
      inhibitory effects of the siRNAs were evaluated for reductions of intracellular
      viral genome copy number and viral titres in the cell culture medium measured by
      Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to
      achieve potent inhibition of SARS-CoV infection and replication. A prolonged
      prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for
      at least 72 h was observed. Combination of active siRNA duplexes targeting
      different regions of the viral genome resulted in therapeutic activity of up to
      80% inhibition. CONCLUSION: Chemically synthesized siRNA duplexes targeting SARS
      CoV genomic RNA are potent agents for inhibition of the viral infection and
      replication. The location effects of siRNAs were revealed at both genome sequence
      and open-reading frame levels. The rapid development of siRNA-based SARS-CoV
      inhibitors marked a novel approach for combating newly emergent infectious
      diseases.

PMID- 15259900
TI  - Infrequent transmission of HIV-1 drug-resistant variants.
AB  - Transmission of drug-resistant variants is influenced by several factors,
      including the prevalence of drug resistance in the population of HIV-1-infected
      patients, HIV-1 RNA levels and transmission by recently infected patients. In
      order to evaluate the impact of these factors on the transmission of drug
      resistant variants, we have defined the population of potential transmitters and
      compared their resistance profiles to those of newly infected patients.
      Sequencing of pol gene was performed in 220 recently infected patients and in 373
      chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal
      drug-resistance profiles of potential transmitters were estimated by weighting
      resistance profiles of chronically infected patients with estimates of the Swiss
      HIV-1-infected population, the prevalence of exposure to antiviral drugs and the
      proportion of infections attributed to primary HIV infections. The drug
      resistance prevalence in recently infected patients was 10.5% (one class drug
      resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis
      revealed significant clustering for 30% of recent infections. The drug-resistance
      prevalence in chronically infected patients was 72.4% (one class: 29%; two
      classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission
      relative to wild-type was reduced both for one class drug resistance (minimal and
      maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011,
      respectively), and for two to three class drug resistance (odds ratios: 0.05 and
      0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels
      explained the low transmission of drug-resistant variants. These data suggest
      that drug-resistant variants and in particular multidrug-resistant variants have
      a substantially reduced transmission capacity.

PMID- 15259901
TI  - Prevalence of lipoatrophy and mitochondrial DNA content of blood and subcutaneous
      fat in HIV-1-infected patients randomly allocated to zidovudine- or stavudine
      based therapy.
AB  - INTRODUCTION: Mitochondrial toxicity resulting from mitochondrial DNA (mtDNA)
      depletion is suggested to be involved in the pathogenesis of lipodystrophy.
      METHODS: We cross-sectionally assessed lipodystrophy both clinically and
      radiographically in patients who, 4 years before, had been enrolled in a
      randomized comparative trial of stavudine- or zidovudine-based therapy. mtDNA
      content was measured in peripheral blood mononuclear cells (PBMCs) and
      subcutaneous adipose tissue from the thigh and back. RESULTS: Twenty-eight of the
      45 patients enrolled in the original trial were included. Despite comparable
      exposure to stavudine or zidovudine (51 and 50 months, respectively), lipoatrophy
      prevalence by intent-to-treat analysis was significantly greater in stavudine
      recipients (82 vs 9%, P=0.0001). Likewise, those allocated to stavudine had
      significantly less peripheral fat. In an analysis restricted to patients who had
      remained on randomly allocated nucleoside reverse transcriptase inhibitors
      (NRTIs), mtDNA in PBMCs decreased after the start of treatment in both groups
      (P<0.0001) (-73% for stavudine and -67% for zidovudine, P=0.11), resulting in
      significantly lower levels in patients with lipoatrophy (P=0.007). The mtDNA
      content in subcutaneous adipose tissue from the thigh, but not from the back, was
      significantly lower in patients allocated to stavudine compared to zidovudine
      (P=0.01). mtDNA in adipose tissue from either location did not differ
      significantly between those with or without lipoatrophy. DISCUSSION: This study
      objectively confirms that regimens containing stavudine are associated with a
      greater risk of lipoatrophy than those containing zidovudine. mtDNA in PBMCs
      markedly declined with both treatments and was lowest in patients with
      lipoatrophy. The lack of difference in mtDNA in adipose tissue from patients with
      as opposed to without lipoatrophy may have been masked by a relative
      preponderance of stromal and vascular tissue in the subcutaneous tissue samples
      from these patients, combined with compensatory mitochondrial proliferation in
      remaining adipocytes. However, our findings may also suggest that the different
      risk of lipoatrophy observed between NRTIs cannot solely be explained by
      differences in mtDNA depletion directly at the level of peripheral adipose
      tissue.

PMID- 15259902
TI  - Simplified volumetric flow cytometry allows feasible and accurate determination
      of CD4 T lymphocytes in immunodeficient patients worldwide.
AB  - The determination of CD4 cells is of crucial clinical importance for patients
      with AIDS. However, the high costs involved represent limitations for CD4 cell
      counting in developing countries. In order to provide an affordable technique, we
      introduced a simplified volumetric counting (SVC) technique without sample
      manipulations and investigated it in a multicentre study. Blood samples from 434
      healthy donors and immunodeficient patients were tested in eight hospital
      laboratories in Europe, Africa and Asia. CD4 cell counts were compared using in
      house flow cytometric methods and the SVC technique. The SVC method was performed
      on a low-cost flow cytometer (CyFlow SL, Partec, Munster, Germany) after 15 min
      antibody incubation without pre-analytic manipulations, such as washing or
      erythrocyte lysing procedures. Linear regression analysis demonstrated a
      correlation of r=0.942 (Europe), r=0.952 (Africa) and r=0.989 (Asia) between the
      SVC technique and the in-house methods. Bland Altman plot analysis of all patient
      data showed a mean bias between the two methods of +26 CD4 cells in favour of the
      SVC technique (measured range: 6-1905 cells/microl; median CD4 cell count:
      388/microl). Three centres used the FACS-count technique (Becton-Dickinson, San
      Jose, Calif., USA) as an in-house method dispensing with pre-analytic
      manipulations. The comparison of SVC and FACS-count method revealed a mean bias
      of +32 CD4 cells/microl (median CD4 cell count: 349/microl). The accuracy of the
      SVC was tested on standards with known CD4 cell counts (n=6) and was shown to be
      95.2%. The low-cost device and the simplified no-lyse, no-wash test procedure
      reduces the costs per determination and facilitates the use of flow cytometry in
      developing countries.

PMID- 15259903
TI  - Psychosocial determinants of adherence to highly active antiretroviral therapy
      among injection drug users in Vancouver.
AB  - BACKGROUND: Sub-optimal adherence to highly active antiretroviral therapy (HAART)
      among injection drug users (IDUs) is a significant concern. As such, there is an
      urgent need to identify psychosocial determinants of adherence that can be
      incorporated into interventions designed to promote optimal adherence. OBJECTIVE:
      To identify psychosocial determinants of adherence to HAART, as well as self
      reported reasons for missing doses of HAART among HIV-infected IDUs. METHODS: We
      developed an eight-item adherence self-efficacy scale comprised of two sub
      scales: adherence efficacy and self-regulatory efficacy. We examined correlates
      between adherence self-efficacy, outcome expectations, socio-demographic
      characteristics, drug use and risk behaviours, social support and HAART adherence
      among 108 HIV-infected participants in the Vancouver Injection Drug Users Study
      (VIDUS). Pharmacy-based adherence to HAART was obtained through a confidential
      record linkage to the province of British Columbia's HIV/AIDS Drug Treatment
      Program. Participants were defined as adherent if they picked-up 95% of their
      HAART prescriptions. Participants were also asked to indicate reasons for missing
      doses of HAART. Logistic regression was used to identify the factors
      independently associated with adherence to HAART. RESULTS: Seventy-one (66%) HIV
      infected IDUs were less than 95% adherent. Forgetting was the most frequently
      cited reason (27%) for missing doses of HAART. Factors independently associated
      with adherence to HAART included adherence efficacy expectations [OR=1.8 (95% CI:
      1.0-3.1); P=0.039] and negative outcome expectations [OR=0.8 (95% CI: 0.7-0.9);
      P=0.027]. CONCLUSIONS: We found low rates of adherence to HAART among IDUs.
      Psychological constructs derived from self-efficacy theory are highly germane to
      the understanding of adherence behaviour, and interventions that address these
      constructs should be developed and tested among HIV-infected drug users.

PMID- 15259904
TI  - Persistence of multidrug-resistant HIV-1 without antiretroviral treatment 2 years
      after sexual transmission.
AB  - OBJECTIVES: To understand the virological mechanisms of 2-year persistence of
      multidrug-resistant virus without selective antiretroviral pressure in HIV-1
      infected patients. PATIENTS AND METHODS: Two patients were contaminated recently
      by their HIV-1-infected partners, who had received, before the transmission, all
      available antiretroviral drugs and who exhibited a severe therapeutic failure.
      The resistance mutations analysis was performed by clonal sequencing of 1.2 kb of
      pol gene in plasma of index and sources patients. Sequencing of HIV-1 DNA was
      performed in PBMCs of index patients. RESULTS: Genotypic testing performed in
      index patients at time of seroconversion showed resistance mutations to three
      classes of drugs. All mutations were linked on the same viral genome and all
      quasispecies carried all mutations. No wild-type virus was detected. The same
      results were found in source patients and showed that all mutations were
      transmitted. In the index patients, all mutations persisted over 2 years without
      antiretroviral treatment. Moreover, the resistance mutations were all archived in
      the cellular reservoir. Viral load and CD4 count of index patients remained
      unchanged during 2 years of follow-up. DISCUSSION: Only multidrug-resistant
      viruses were detected in the source patients and could be transmitted in index
      patients. In the latter, an expansion of predominant multidrug-resistant
      quasispecies and the 'archival' of all mutations were observed. These results
      explain the persistence of mutations and suggest that it is highly difficult to
      return to a wild-type viral population, sensitive to an antiretroviral treatment.
      The treatment of index patients is limited and the major risk is the transmission
      of these multidrug-resistant viruses. This work was presented in part in the XII
      International HIV Drug Resistance Workshop, Los Cabos, Mexico, June 2003; and in
      the 2nd IAS Conference on HIV Pathogenesis & Treatment, Paris, France, July 2003.

PMID- 15259905
TI  - Pharmacokinetics of once-daily saquinavir/ritonavir in HIV-infected subjects:
      comparison with the standard twice-daily regimen.
AB  - OBJECTIVE: To evaluate the steady-state pharmacokinetics and safety of two once
      daily saquinavir/ritonavir (SQV/RTV) regimens, 1600/100 and 2000/100 mg, in HIV
      positive patients. METHODS: Eighteen HIV-infected adults treated with the
      standard twice-daily SQV/RTV 1000/100 mg regimen were enrolled in this open
      label, two-phase, crossover pharmacokinetic study. The steady-state
      pharmacokinetics of SQV administered with 100 mg RTV were investigated following
      once-daily doses of 1600 mg or 2000 mg or a twice-daily dose of 1000 mg. Plasma
      drug concentrations were determined by high performance liquid chromatography
      tandem mass spectrometry and pharmacokinetic parameters were calculated using a
      non-compartmental model. RESULTS: Compared with SQV 1000 mg twice daily, the Cmax
      of SQV following a 1600 mg and 2000 mg dose increased in a dose-proportional
      manner [geometric mean (95% CI) 1915 (1656-2850) ng/ml for 1000 mg, 2782 (2249
      4330) ng/ml for 1600 mg and 4179 (3429-6105) ng/ml for 2000 mg doses,
      respectively]. SQV Ctrough values were 539 (453-1011), 106 (76-223) and 231 (75
      822) ng/ml, respectively. A SQV Ctrough value greater than 100 ng/ml was achieved
      in all subjects on the twice-daily regimen, in 9/18 (50%) subjects on the
      1600/100 mg once-daily regimen, and in 14/17 (82%) subjects on the 2000/100 mg
      once-daily regimen. The once-daily regimens were well tolerated, with mild-to
      moderate gastrointestinal symptoms being the only events reported by a small
      number of patients. CONCLUSION: This is the first study to evaluate the
      pharmacokinetics of once-daily SQV/RTV 2000/100 mg in HIV-infected subjects. Our
      findings suggest that this regimen may be an alternative to twice-daily 1000/100
      mg doses and should be further evaluated in efficacy studies. The data indicate
      that most patients (14/17) on once-daily 2000/100 mg achieve trough
      concentrations above target values (determined for HIV wild-type) for efficacy of
      SQV with the use of just 100 mg RTV/day and with good tolerability.

PMID- 15259907
TI  - Destabilization of the non-pathogenic, cellular prion-protein by a small
      molecular drug.
AB  - The presence of the normal cellular prion-protein (PrPc) is a prerequisite for
      the development of fatal, neurodegenerative diseases called transmissible
      spongiform encephalopathies (TSEs). We discovered a new biological activity of
      the well-known coumarin antibiotic novobiocin; the treatment of eukaryotic cells
      with novobiocin induces the rapid depletion of PrPc. This activity is shared by
      coumermycin A1, another coumarin with a related molecular structure. Novobiocin's
      effects on the prion-protein are time- and dose-dependent. No permanent damage to
      the treated cells was observed, which continue to proliferate after cessation of
      drug exposure. Most of the cellular proteins are unaffected by novobiocin
      treatment. Pretreatment with geldanamycin, an inhibitor of the aminoterminal
      ATPase of heat-shock protein 90 (Hsp90) partially antagonizes novobiocin's
      depletory activity. Concurrent treatment with the protease inhibitor chymostatin
      completely prevents PrPc loss. Here we show that the stability of the normal
      cellular prion-protein may be targeted pharmacologically. These findings open up
      a hitherto unknown avenue to the study of TSEs in general and may have
      therapeutic implications.

PMID- 15259906
TI  - Antiretroviral treatment alters relationship between MCP-1 and neurometabolites
      in HIV patients.
AB  - OBJECTIVE: The relationships between neurometabolites and macrophage
      chemoattractant protein (MCP-1) in serum and cerebrospinal fluid (CSF) were
      evaluated in HIV patients before and after antiretroviral treatment. DESIGN:
      Prior studies found higher CSF MCP-1 levels in patients with HIV-associated
      dementia compared to those in neuroasymptomatic. We hypothesized that CSF MCP-1
      levels would correlate inversely to neuronal metabolites [including N-acetyl
      compounds, glutamate+glutamine, as assessed by principal component analyses
      (PCA)] and positively to glial metabolites (including myo-inositol and choline
      compounds). METHODS: Thirty-nine antiretroviral-naive HIV patients were evaluated
      prospectively with proton magnetic resonance spectroscopy (1H MRS), and serum and
      CSF MCP-1 measurements prior to highly active antiretroviral therapy (HAART); 31
      of these patients completed follow-up studies after 3 months of HAART but only 24
      had follow-up CSF studies. RESULTS: After HAART, brain metabolites and clinical
      signs showed no change despite improvements in systemic (CD4 counts, plasma viral
      load, MCP-1) and CSF (viral load and MCP-1) variables. CSF, but not serum, MCP-1
      levels correlated inversely with the neuronal component (from PCA) prior to
      treatment (r=-0.59, P=0.0008). Conversely, after 3 months of HAART, the glial
      component (from PCA) correlated positively with CSF MCP-1 levels (r=0.70,
      P=0.0002; ANCOVA interaction for treatment status, P=0.003). CONCLUSIONS: These
      findings suggest that higher CSF MCP-1 levels are associated with neuronal
      dysfunction in untreated patients. After 3 months of HAART, the decreased
      systemic factors (viral burden, systemically derived MCP-1) no longer associate
      with neuronal dysfunction, but subjects with the strongest glial response in the
      brain continue to produce the highest levels of MCP-1.

PMID- 15259908
TI  - IL-7/IL-7 receptor system regulation following IL-2 immunotherapy in HIV-infected
      patients.
AB  - Interleukin-2 (IL-2) and IL-7 are the most intriguing molecules in immune-based
      HIV infection treatment. An in vitro IL-2/IL-7 cross-talk due to IL-2-driven IL-7
      receptor-alpha-chain (IL-7R alpha) down-modulation, potentially blocking IL-7
      signalling has been described. We investigated the in vivo IL-2 effect on IL-7/IL
      7R system, measuring free IL-7, and IL-7R alpha CD4 and CD8 in 12 HIV-positive
      patients enrolled in a randomized IL-2 trial. Compared to HAART alone, IL-2
      induced a parallel expansion in total and naive CD4, TRECs and IL-7 plasma
      levels, with no IL-7R alpha CD4 and IL-7R alpha CD8 changes (P>0.05), suggesting
      that in vivo IL-2 boosts IL-7 production without down-modulating IL-7R alpha,
      preserving IL-7-mediated T-lymphocyte homeostatic regulation. Our data confirm
      the pivotal role of IL-2 and IL-7 in the regulation of T-lymphocyte homeostasis
      in HIV infection.

PMID- 15259909
TI  - Epstein-Barr virus load correlating with clinical manifestation and treatment
      response in a patient with angioimmunoblastic T-cell lymphoma.
AB  - Epstein-Barr virus (EBV)-associated lymphoma may arise secondary to
      angioimmunoblastic T-cell lymphoma (AITL). The prognosis is poor despite
      chemotherapy and experimental therapies. We report on a 40-year-old woman with
      AITL without obvious immunodeficiency in which EBV-associated lymphoma developed.
      The occurrence and size of enlarged lymph nodes correlated strongly with the EBV
      load in serum (EBVL). Treatment with valacyclovir at the early stage resulted in
      a drastic more than 3 log10 decrease of EBVL and complete remission. However,
      valacyclovir had to be stopped after 6 months due to side effects, and the
      lymphoma reoccurred 3 months later associated with increasing EBVL. Eventually
      started cytotoxic chemo- and anti-CD20 therapy resulted only in partial
      remission. The lymphoma progressed and 33 months after it was diagnosed the
      patient died. This case report demonstrates the close association of EBVL and
      AITL and a beneficial effect of antiviral therapy at an initial stage of disease
      manifestation.

PMID- 15259910
TI  - Highly active antiretroviral therapy for injection drug users: physician
      recommended strategies for enhanced adherence.

PMID- 15259911
TI  - Juvenile periodontitis--a review of literature.
AB  - Juvenile Periodontitis (JP), a condition that was previously regarded as a rare
      disease has of recent come into the fore as a model for the study of inflammatory
      periodontal disease. It has also been found to be considerably more common in
      occurrence than previously thought. This article reviews the literature on the
      epidemiology, aetiology, pathogenesis, clinical features, histopathological and
      immunological findings, differential diagnosis, treatment and prognosis of JP.
      The objective of this article is to give the clinician the current opinions of
      researchers in all aspects of the disease as compared to previous age long views.
      It is observed that there are contradictory reports on the epidemiology, etiology
      and treatment of the disease and hence the need for further studies in these
      areas.

PMID- 15259912
TI  - Prevalence of cigarette smoking in young Nigerian females.
AB  - Cigarette smoking is a very important public health problem globally, with
      patterns of smoking varying in different regions of the world. The negative
      impact of smoking on health is well known but the increasing rate of smoking
      amongst the youth including females is note worthy. The objective of this study
      is to determine the prevalence of smoking in young Nigerian females with a view
      to defining the size of this social problem and outlining possible control
      measures. The setting for the study was secondary (post-primary) schools in
      Anambra State, South east of Nigeria. The study, a cross-sectional survey,
      involved eight (8) schools selected by multistage sampling technique. A
      Structured questionnaire was designed for the study. A total of 1,200 female
      secondary school students were involved. The mean age of the respondents was
      16.06 +/- 1.36 years. The main religious denominations were Roman Catholic 69.7%,
      Anglicans 23.6%, Pentecostal 5.7%, Islam 0.4% and others 0.4%. Ninety two point
      seven percent (92.7%) were single, 2.9% were married and 4.4% engaged. Fifty
      seven point four percent (57.4%) were day students while 42.6% were boarders.
      Smoking prevalence was 7.7%. Smoking was started at the mean age of 12.6 +/- 3.8
      years. The number of cigarettes smoked per day has a median of 2 sticks, Marital
      status significantly affected smoking prevalence as the married had more tendency
      to smoke than the unmarried. Though the number of day students who smoked were
      more than the boarders, the significance could not be demonstrated statistically
      due to the small number of subjects who smoke. Parents educational status did not
      show any significant influence on the smoking habit. We conclude that the
      prevalence of cigarette smoking in young Nigerian females is relatively low.
      Intervention at this stage will be timely but effective strategies to curb the
      habit will require identification of other factors that may be contributing to
      the social menace.

PMID- 15259914
TI  - Factors associated with growth faltering in children from rural Saudi Arabia.
AB  - Recent studies on the growth of children in Saudi Arabia have revealed that
      children under two years of age suffer from faltering growth when compared with
      the American reference population. The present study aims to identify parental
      and child characteristics associated with faltering growth among the children in
      a rural area of Saudi Arabia. A cross-sectional study of all women with a child
      less than three years of age in a rural community in NorthWestern part of Saudi
      Arabia was undertaken. Anthropometric measurements, socio-demographic and
      fertility variables were collected using a structured questionnaire. The
      indicators of growth were derived from the data and univariate and logistic
      models fitted to determine potential risk factors. There were 332 children, sex
      ratio 1.35 and 94.3% were less than 2 years of age. A low frequency (1.5%) had
      low weight for height, 11.4% low weight for age and 36.1% low height for age when
      compared with the American NCHS reference population. Multiple logistic
      regression suggested birth space > 2 years (OR = 0.44, 95% CI = 0.25 - 0.77),
      father's with primary or intermediate education (OR = 0.45, 95% CI = 0.25-0.90),
      birth weight > 2500 gms. (OR = 0.8, 95% CI = 0.03-0.75), male birth (OR = 2.60,
      95%. CI = 1.54-4.59) were variables statistically and independently associated
      with faltering growth. The pattern of growth of children under 2 years deviated
      negatively from their NCHS-WHO reference. This is similar to the previous
      findings from urban communities in Saudi Arabia. This growth faltering could be
      attributed partly to the inadequacy of the reference to compare growth pattern of
      children in all geographical areas, of the world. While the effects of different
      dietary habits may not be ruled out, it may be important to develop a different
      anthropometrics and nutrients growth chart that could be more appropriate to
      compare variation of infant growth in all nations of the world.

PMID- 15259913
TI  - Sexual activity among adolescents in Ilorin, Kwara State, Nigeria.
AB  - With the aid of a self-administered questionnaire, sexual activity was
      investigated among 1,200 students aged 10-19 years. Two hundred and sixty-four
      (23.7%) respondents indicated they were sexually active. The mean age at first
      intercourse was 11.3 years (SD=5.8 years), while the average number of sex
      partner was 2-3. Multiple sexual partners were found in 99 (69.2%) of the males
      and in 16 (32.7%) of the females (P < 0.05). Males were more sexually active, 189
      (32.8%) compared with 73 (13.7%) females (P=0.000001; RR=2.4 (1.88-3.05). Two
      hundred and fifty-three (23.4%) ofthose respondents who claimed to be highly
      religious had sexual intercourse compared with 7 (50%) of those who claimed not
      to be religious (P=0.02; PR=0.47 (0.27-0.80). Those whose parents lived together
      were less likely to be sexually active. 184 (21.2%) versus 47 (34.8%) (P=0.005).
      It is therefore concluded that our adolescents especially males remain sexually
      active. It also demonstrates the dramatic lowering of age at first intercourse.
      Family supervision and level of religious activity were recognized as factors
      that have significant impact on sexual activity. Preventive efforts must
      therefore focus on these issues with the active involvement of the Pediatrician,
      parents and religious leaders.

PMID- 15259915
TI  - The pattern of stillbirth in a secondary and a tertiary hospital in Ibadan,
      Nigeria.
AB  - Stillbirths contribute a remarkable proportion to perinatal mortality in
      developing countries. Perinatal mortality rate (PMR) is still very high in these
      countries, ranging from 60 to 120 per 1000 total births, compared with 10 to 20
      per 1000 total births in Europe. A descriptive review epidemiological study was
      carried out over a 3 year period, 1978-1980 inclusive, in two major hospitals in
      Ibadan city, capital of Oyo State in the South Western part of Nigeria, using
      structured questionnaires. The study revealed an overall prevalence rate of
      stillbirths of 63/1000 total births. Fresh stillbirths with no visible congenital
      malformations predominate. Some of the risk factors observed from this study to
      be associated with stillbirths in Nigeria include teenage and advanced maternal
      age (< or = 19 years and > or = 35 years), high party and past history of
      spontaneous abortions. As preventive measures, efforts should be made to improve
      antenatal and obstetric services. The data collected serves as a baseline for
      further research on this topic.

PMID- 15259916
TI  - Antibacterial and antifungal activities of Quassia undulata and Quassia amara
      extracts in vitro.
AB  - Extracts of Quassia undulata and Quassia amara (Simaroubaceae) were screened for
      in vitro antibacterial and antifungal properties respectively. A total of eight
      extracts, comprising hexane and methanol extracts of the leaves and stems of each
      of the two plants were investigated. At a concentration of 5 mg/ml all eight
      extracts exhibited marked antibacterial and antifungal activities in most cases
      higher than the standard reference drugs included in the study. The extracts
      inhibited the growth of Escherichia coli, Streptococcus faecalis, Stapylococcus
      aureus and Aspergillus niger, even when the standard reference drugs utilized in
      the study did not. Quassia amara leaf methanol extract singularly exhibited the
      highest activities in both assays, which included the use of six clinical strains
      of bacteria and five fungi. The agar cup (10 mm diameter) diffussion and broth
      dilution techniques were used in both assays, utilising eleven human pathogenic
      microorganisms. Ampicillin and tioconazole were also included in the assay as
      reference compounds, while methanol was used as control. Diameter of zones of
      inhibition ranged between 11.0-29.0 mm for the tested extracts/drugs. All the
      extracts have shown impressive activities against the commonly encountered
      microorganisms and have thus confirmed the folklore uses of the plants in the
      African ethnomedicine.

PMID- 15259917
TI  - Determination of physicochemical properties of halofantrine.
AB  - The physicochemical properties of halofantrine hydrochloride (HF HCl)--a
      phenanthrene methanol antimalarial, were determined practically in this study
      since such experimental values are still unknown. The solubility in different
      solvents were determined and found to be 0.67%w/v in methanol (slightly soluble);
      0.4%w/v in both n-octanol and acidified acetonitrile (slightly soluble); 0.09%w/v
      (very slightly soluble) and less than 0.002%w/v in warm water (50 degrees C)
      (practically insoluble). Halofantrine hydrochloride was found to be practically
      insoluble in water (at room temperature), n-hexane and phosphate buffer solution
      of pH 7.4. The partition coefficient between n-octanol and water gave a log p in
      the range of 3.20-3.26 (mean 3.20 +/- 0.04) and this was at variance with the log
      P of 8.5 estimated theoretically in literature. The value also confirms the
      lipophilicity of HF HCl. The ionisation constant (pKa) determined in partly
      aqueous solvent (40% methanol) ranged between 8.10 and 8.20 (mean 8.18 +/- 0.05)
      and confirms the monobasicity of halofantrine. This value also differed from the
      theoretical estimation of 9.6. The values obtained confirm the often
      unpredictable and erratic absorption of HF HCl, which bears direct relationship
      to the physicochemical properties and support the need for better formulations
      with improved drug delivery potentials.

PMID- 15259918
TI  - Pattern of tooth loss in Nigerian juvenile and plaque-induced chronic
      periodontitis patients.
AB  - The aim of this study was to determine the pattern of tooth loss in chronic
      periodontitis patients and hence help the clinician to plan preventive treatment
      against the loss of these teeth. Dental record notes of all the subjects, the
      periapical radiographs and actual intra-oral examinations of the juvenile
      periodontitis patients were done to determine the number and types of tooth loss.
      It was observed that the pattern of tooth loss in both groups of chronic
      periodontitis (plaque Induced periodontitis (PIP) and juvenile periodontitis (JP)
      was different as the most frequently lost teeth in PIP was incisors and lower
      incisor in JP while the least lost in PIP was the upper canines and the lower
      premolars in JP.

PMID- 15259919
TI  - The quality of life of chronic epileptic patients in Ibadan, Nigeria.
AB  - Epilepsy is a disease that significantly impairs the quality of life of the
      sufferers. Measures of quality of life have been developed to assess the overall
      impact of management on the patients. While studies on quality of life have been
      previously carried out in Nigerians, a standardised and validated inventory has
      not been used for this purpose because these are just being developed. Thirty-two
      epileptics (24 males and 8 females) attending the Neurology clinic of the
      University College Hospital, Ibadan, were studied. Each subject had complete
      physical examination and elecroencephalography. A short screening quality of life
      questionnaire (QOLIE 10) was administered to the subjects during routine clinic
      visits. The commonest aspect of quality of life affected in the subjects was
      feeling of energy, which was impaired in 15 (46.8%) subjects. This was followed
      by memory problems in 11 (34.4%). Fear of experiencing the next seizure was
      reported by eight (25.8%) of subjects. Only five (16.7%) and three (10.3%) of the
      subjects respectively reported work and social limitations like attending social
      occasions. No subject reported difficulty with driving or operating machinery, or
      mental disturbances. Energy and memory deficits are the major problems affecting
      the quality of life of epileptics in this study. Most subjects did not consider
      physical and social limitations important.

PMID- 15259920
TI  - The Ibadan glaucoma study.
AB  - To obtain epidemiological data on the prevalence and risk factors for open angle
      glaucoma in hospital workers of African origin, and investigate appropriate
      methods of a rapid, cost-effective screening procedure for glaucoma. A cross
      sectional study of workers in the University College Hospital (UCH) Ibadan, using
      a structured questionnaire for data collection. The variables available for data
      analysis include workers demographic characteristics, visual acuity, pupil
      status, intraocular pressure, cup-disc ratio, central visual fields, family
      history of glaucoma, chronic diseases such as hypertension and diabetes. The data
      was analysed with EPI-INFO version 6.02 for simple analysis, while the SPSS
      package was used for multivariate analysis. A total of two thousand, one hundred
      and nine (2,109) UCH workers participated in the screening exercise for glaucoma.
      A high majority of the workers 1794 (85.1%) were negative to the diagnosis of
      glaucoma, while the remaining 315 (14.9%) were suspected to have glaucoma out of
      which 57 (2.7%) were confirmed as definite glaucoma cases. The prevalence of
      glaucoma among UCH workers was 27 per 1000, 95%, confidence interval = 20 per
      1000, 35 per 1000. Factors associated with glaucoma were relative afferent
      pupillary defect, cup-disc ratio greater than 0.7, intraocular pressure, family
      history of glaucoma and the presence of chronic diseases such as diabetes. The
      left eye appears to have a higher probability of ocular problems compared with
      the right eye. The prevalence of glaucoma among hospital workers was 2.7% The cup
      disc ratio appears to be a better diagnostic tool for glaucoma since it gives the
      best positive predictive value (with a cut-off point of 0.7) than all other
      variables.

PMID- 15259921
TI  - Caring for the terminally ill: what do the doctors think?
AB  - Patients' perception of end-of-life events varies with cultural norms and values,
      and expectations may differ from clinicians practice and actions. In contemporary
      practice, conflict of ideas often results in patients discharging themselves
      against medical advice. Clinicians (67) that have been in medical practice for at
      least five years at the main tertiary hospital in Benin City were interviewed
      with a semi-structured questionnaire. The main outcome measured was clinicians'
      attitude towards caring for the terminally ill patients and physician assisted
      suicide (PAS). The mean age of the clinicians was 36.89 +/- 7.57, 11 females and
      56 males. Twenty-six clinicians (40%) do not routinely record in the case notes
      details of their discussion on prognosis with their patients. Forty one (62.1%)
      clinicians will not support life while patients are on palliative care, while
      49/66 (74.2%) will transfuse their patients with blood. Thirteen (31.7%) will not
      support life, and will not transfuse blood. Fifty seven (85.1%) clinicians will
      not support euthanasia, 8 of the 9 physicians who will support PAS are males,
      while 6 of the 9 clinicians that will grant patient's request for PAS are
      gynaecologists. All (17) clinicians in Internal Medicine specialty will not
      support PAS, while 51/67 (77.3%) clinicians are of the opinion that patients
      should be routinely informed of the prognosis of their disease. Documentation of
      physician-patients interactions is poor amongst clinicians. Most will not support
      life and physician-assisted suicide for the terminally ill patients. However, in
      clinical practice most will transfuse their patients on palliative care with
      blood and give other life support treatment; an apparent dissociation between
      what clinicians think and what is practised.

PMID- 15259922
TI  - Sonographic evaluation of plaque morphology in haemodynamic and non-haemodynamic
      symptomatic carotid artery stenoses.
AB  - A prospective duplex ultrasound and Colour Doppler imaging studies were performed
      on 52 consecutive patients with 63 carotid arteries (11 patients with bilateral
      carotid interrogation). The cases were classified into two study groups--non
      haemodynamically (< 50%) and haemodynamically (= 50%) significant stenoses in
      relation to clinical events and carotid plaque echomorphology. Of the 63 carotid
      arteries that were evaluated, 36 (57.1%) revealed non-haemodynamic and 27 (42.9%)
      haemodynamic stenoses. Our study confirmed that more than half of the cases with
      hemispheric symptoms (stroke and TIA) were related to nonhaemodynamic stenosis
      accounting for 53.7%. While heterogeneous and homogeneous plaques were seen in
      both study groups with hemispheric symptoms, no heterogeneous plaque was seen in
      haemodynamic stenosis with non-hemispheric symptoms. No statistically significant
      differences were seen between heterogeneous and homogeneous plaques in non
      haemodynamic and haemodynamic cases. Predominantly hypoechoic stenoses,
      representing thrombotic materials are more common in haemodynamic cases of stroke
      accounting for 64.3% and in 76.9% of non-haemodynamic cases in TIA. Plaque
      surface irregularity and ulceration did not seem to be related to the severity of
      stenosis as there was no statistically significant difference in the frequencies.
      However, while irregularly surfaced plaques are of equal frequency in non
      haemodynamic and haemodynamic cases in stroke, there was no ulceration in non
      haemodynamic cases. There was preponderance of irregular surfaced plaques in non
      haemodynamic and ulceration in haemodynamic cases in TIA. Our study showed higher
      frequency of smooth plaque in relation to hemispheric and non-hemispheric
      symptoms in non-haemodynamic stenosis and mainly ulceration/irregular plaques in
      haemodynamic stenosis. The trend of plaque echomorphology and surface
      characteristics in the study groups were highlighted. The pathogenesis of the
      symptoms was discussed. In conclusion, there is more to the occurrence
      hemispheric symptoms than the severity of the stenosis. While flow-limiting
      effects of stenosis in conjunction with or without embolic potentials are causes
      of symptoms in haemodynamic, embolic potentials are the main factors in non
      haemodynamic cases.

PMID- 15259923
TI  - Women with painful breasts without palpable masses: do they really need a
      mammogram?
AB  - This prospective study was carried out over a period of 36 months, and the study
      population was, all the women (726) referred for mammograms on account of painful
      breast(s) without palpable masses. They were matched with the same number of
      asymptomatic women in a control group. The mammographic findings in the women
      with painful breast(s) and no palpable masses were normal in 639 (88%), benign in
      80 (11%), suspicious in 2 (0.3%) and malignant in 5 (0.7%). In the control group
      mammograms showed normal breasts in 625 (86.1%), benign and suspicious lesions in
      87 (12%) and 7 (1.0%) respectively. Malignant lesions were recorded in 7 (0.9%)
      women. The prevalence of breast cancer was similar in women with painful
      breast(s) and the control asymptomatic cases. Our reports show that inspite of
      the pain experienced by the women in this study mammography had a low diagnostic
      yield of malignant lesions, just as it was found in the control group.
      Mammography therefore, in these patients will only provide reassurance.

PMID- 15259924
TI  - Therapeutic effect of TENS on post-IMF trismus and pain.
AB  - The study set out to investigate the therapeutic effect of Transcutaneous
      Electrical Nerve Stimulation (TENS) in the alleviation of pain and post-IMF
      trismus, in patients undergoing jaw exercises to hasten mouth opening after being
      treated for fractures of the mandible. Two groups of patients, with 10 patients
      in each group, were used for the study. The groups were the experimental and the
      control groups. They were all treated for mandibular fractures, and had their
      jaws immobilized for 6 weeks, immediately after which they were started on jaw
      exercises. The Inter-incisal distances and number of acceptable wooden spatulae
      that the jaws could accommodate were noted and recorded. The experimental group
      was then placed on the TENS therapy for 20 minutes, after which the new inter
      incisal distances and the number of acceptable wooden spatulae were recorded. The
      control group had no TENS therapy; the patients only waited for 20 minutes
      without any stimulation, before the new inter-incisal distances and the number of
      acceptable wooden spatulae were measured and recorded. It was observed that the
      inter-incisal distance and the number of acceptable wooden spatulae significantly
      increased in patients in the experimental group compared to the control group. It
      was concluded that TENS could be useful in relieving the pain associated with
      forced mouth-opening exercises aimed at overcoming trismus caused by muscle
      spasm, which is associated with prolonged immobilization of the jaws for the
      treatment of facial fractures.

PMID- 15259925
TI  - Relation of electrocardiographic left ventricular hypertrophy to blood pressure,
      body mass index, serum lipids and blood sugar levels in adult Nigerians.
AB  - Left ventricular hypertrophy (LVH) is considered an independent risk factor even
      in the absence of systemic hypertension. Electrocardiographic (ECG) LVH with
      repolarisation changes has been found in some countries to carry more coronary
      risk than LVH alone. How far this observation is true among adult Nigerians is
      not known. We therefore decided to study adult Nigerians with ECG-LVH with or
      without ST-T waves changes and compare them with normal age matched controls
      (without ECG-LVH) in relation with established modifiable risk factors such as
      systemic hypertension (BP), body mass index (BMI), fasting blood sugar (FBS) and
      serum lipids such as total cholesterol (Tc), low density lipoprotein cholesterol
      (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG).
      Adult Nigerians who were consecutively referred to the ECG laboratory were
      randomly recruited. Three hundred patients were studied. Their blood pressures
      (BP) as well as body mass indices were recorded after recording their resting 12
      read ECG using portable Seward 9953 ECG machine. Their waist-hip ratio (WHR) was
      also recorded. Blood samples were taken to determine their fasting blood sugar
      and serum lipids. Their ECG tracings were read by the cardiologists involved in
      the study while the blood samples were analysed by the chemical pathologist also
      involved in the study. At the end of the ECG reading, the patients were divided
      into 3 groups according to whether there was no ECG-LVH (control group A), ECG
      LVH alone (group B), and ECG-LVH with ST-T waves changes (group C). One hundred
      and fifty (50%) patients belonged to group A, 100 (33.3%) patients to group B and
      50 (16.7%) group C. Group B patients were found to have higher modifiable risk
      factors in form of systemic BP. Tc, LDL-C, and WHR compared to group A. However,
      the group C patients had increased load of these coronary risk factors in terms
      of BP elevation, higher BMI, FBS, and scrum cholesterol compared to group B. In
      addition, more female patients were involved in group C. The mean age of group C
      patients compared to group B was also significantly higher (P<0.001) even though
      no significant age difference was noted between group C and group A patients. It
      is concluded that Nigerians with ECG-LVH with ST-T waves changes have increased
      risk of cardiovascular risk factors compared to normal group A patients and even
      patients with EGC-LVH (group B) alone. Hence, they represent subset of patients
      to be aggressively followed up with multiple risk factors intervention.

PMID- 15259926
TI  - Complement levels and leucocyte phagocytosis in newborn babies.
AB  - Newborn babies face higher risk of infection than adults, but the immunological
      basis of this observation is yet to be fully explained particularly in babies of
      different gestations and birth weights. Sixty-two (62) adults, 55 full-term
      babies, 18 low birth weight babies and 44 normal birth weight babies were
      considered for the study. B-lymphocytes and T-lymphocytes were enumerated by EAC
      rosette and E-rosette respectively. Leucocyte migration and intracellular killing
      were assessed by percentage migration index (%M.I), percentage Candidacidal index
      (%C.I) and bacterial stimulated nitroblue tetrazolium (NBT) dye reduction index
      (%NBT) respectively. Also, serum levels of C3 and C5 were measured by single
      radial immuno-diffusion method. Percentage T cell, C3, C5, %NBT and %C.I were
      lowest in low birth weight babies but % B cell was lowest in full term babies
      while normal birth babies had least %M.I. The present study suggests that
      gestational age and birth weight affect different aspects of immune response.

PMID- 15259927
TI  - A post rotation survey of medical students attitude to radiology.
AB  - The objective of the study is to determine the effect of a three-week radiology
      rotation on the attitudes and knowledge of medical students about the specialty.
      It was found that the students believed in the relevance of radiology in the
      medical school curriculum and its importance to future medical practice. There
      was acceptable level of awareness of radiation protection. However, the rotation
      failed to change the misconception of Radiologists enormous workload with
      resultant bias to the specialty. It is concluded that the rotation had a mixed
      effect on student's knowledge and perception of radiology. This finding is
      comparable with other studies done in industrialized countries. Measures aimed at
      improving the unfavourable attitudes are suggested.

PMID- 15259928
TI  - Prevalence of pregnancy related oral granuloma in a Nigerian population group and
      the possible role of contraceptives.
AB  - A clinicopathological survey on pregnancy related tumours was carried out on 400
      randomly selected pregnant Nigerian women. Fifteen (15) cases of pregnancy
      granuloma or 'epulis gravidanum' were found. Of these subjects, 287 representing
      71.8 percent were on birth control before conception, while 113 or 28.2 percent
      were not. Nine (9) cases of pregnancy tumour were found in the group on birth
      control pills and six (6) in the group not on birth control representing an
      incidence of 3.1 and 5.3 percent respectively. Literature review indicate a
      general incidence of between 0-2.5 percent. Five of the granuloma regressed post
      partum, while ten were excised. Patients were followed 1-2 years post partum and
      no recurrence was recorded, even in patients who have re-commenced on
      contraceptives.

PMID- 15259929
TI  - Use of limbal and central anterior chamber depth measurements in detecting eyes
      with gonioscopically occludable angles and primary angle closure glaucoma in
      Ibadan.
AB  - The routine use of gonioscopy for the evaluation of drainage angles in developing
      countries is not always done because of the busy clinics. The purpose of this
      study was to evaluate the performance of 2 tests: Peripheral Anterior Chamber
      Depth (PACD) measurement and Central Anterior Chamber Depth (CACD) measurement in
      detecting occludable angles and primary angle closure within subjects with
      primary glaucoma and control subjects. Two hundred and forty subjects with
      primary glaucoma and a control group of 250 subjects were studied. PACD was
      measured with the Van Herrick's method while CACD was measured by the technique
      described by Lowe. The findings were compared to the gonioscopic appearance of
      the drainage angles in the two groups. PACD gradings 0 to 2 correctly identified
      28 out of 36 eyes (77.8%) of subjects with PACG who had gonioscopically closed
      angles. The test identified correctly 168 out of 204 eyes (82.4%) with
      gonioscopically open angles among subjects with primary glaucoma. Among subjects
      with no glaucoma, PACD gradings 0 to 2 correctly identified 12 out of the 14 eyes
      with gonioscopically occludable angles, while the test identified 238 eyes
      without occludable angles, gonioscopy identified 236 out of 250 of such eyes. A
      CACD less than 2.5 mm was present in only 21 eyes of 36 eyes with occludable
      angles by gonioscopy among those with PACG. In the other 15 eyes with occludable
      angles, CACD was more than 2.5 mm. PACD performed well in detecting occluded
      angles in this study, CACD was useful but less so than PACD in established cases
      of PACG. Subjects with PACG but whose CACD was 2.5 mm or more may have plateau
      iris. PACD and CACD are both useful methods in identifying occludable angles in
      eyes of Nigerian subjects studied.

PMID- 15259930
TI  - Unusual presentation of NOMA: a case report.
AB  - A case of noma with involvement of other parts of the body from extension and
      spread of cancrum lesion in the oral cavity and primary herpetic stomatitis in a
      two-year-old male patient is reported. The possible routes of infection to other
      parts of the body are discussed. It is expected that this case report will
      stimulate the awareness of health practitioners to this unusual presentation of
      cancrum oris.

PMID- 15259931
TI  - Association of nephrotic syndrome with bronchial asthma: two case reports.

PMID- 15259932
TI  - What is the potential for utilizing the resources in sludge?
AB  - The successful strategy for water protection by biological wastewater treatment
      results in a sludge production of about 20 to 40 kg dry matter per population
      equivalent and year. In the context of regional material fluxes, sewage sludge
      has a low resource potential and a low pollution potential despite the fact that
      it can be characterised as a sink, concentrating wastewater compounds. The mass
      flow of nutrients (N, P) in the sewage sludge is comparatively small as compared
      to the losses of nutrients in agriculture. The most valuable element in the
      sludge is phosphorus, as the availability of phosphorus for the production of low
      cost mineral fertiliser is limited. The most economical means of P-recycling is
      agricultural sludge application, which can also be seen as the option with the
      lowest loss of all valuable compounds of the sludge, and the lowest increase of
      entropy. The reliability of this disposal route for the treatment plant operator
      depends on several major pre-requisites: * reliability in regard to hygiene *
      reliability in regard to long-term soil protection public acceptance
      (politicians, media) * acceptance by all parties involved in sludge application
      and its consequences (farmers, farmer unions, land owners, food industry, food
      trade, retailers, consumers, consumer associations, NGOs, etc.) Only the first
      two prerequisites can be based on scientific research and risk assessment. As a
      consequence, only for these two aspects can quality criteria and adequate
      procedures be developed and introduced into a legal framework and quality
      assurance procedures. The latter two pre-requisites must be addressed in terms of
      sociology, psychology and political science and have a strong educational aspect.

PMID- 15259933
TI  - Sustainable sludge management--what are the challenges for the future?
AB  - Sewage sludge is a serious problem due to the high treatment costs and the risks
      to environment and human health. Future sludge treatment will be progressively
      focused on an improved efficiency and environmental sustainability of the
      process. In this context a survey is given of the most relevant sludge treatment
      options and separate treatment steps. Special attention is paid to those
      processes that are simultaneously focused on the elimination of the risks for
      environment and human health and on the recovery or beneficial use of the
      valuable compounds in the sludge such as organic carbon compounds, inorganic non
      toxic substances, phosphorus and nitrogen containing compounds. Also, a brief
      assessment is given of the specific future technological developments regarding
      the various treatment steps. Furthermore, it is discussed how to assess the
      various pathways which can lead to the required developments. In such an
      assessment the technical and economic feasibility, the environmental
      sustainability, the societal acceptance and the implementation route are
      important factors. The optimal approach also strongly depends on the local and
      regional situation of concern and the relevant current and future boundary
      conditions.

PMID- 15259934
TI  - Contaminants in sludge: implications for management policies and land
      application.
AB  - Policies on sludge (or biosolids) management vary widely, particularly when
      decisions must be made on what to do with the final product. This paper examines
      the two principal rationales with which such decisions are made, and through
      which scientific knowledge is included in the process. These rationales are risk
      analysis (risk assessment and management), and the criterion of sustainability.
      Both are found to be potentially arbitrary due to the difficulty in defining the
      individual constituents necessary to relate environmental phenomena to
      environmental policy. To place the difficulties in a practical context, this
      paper presents research results from three recent projects concerned with
      contaminants in sludge (phosphorus, flocculant polymers, and polymer-surfactant
      aggregates), and uses the findings to exemplify the dilemma encountered in policy
      making. A path forward is proposed.

PMID- 15259935
TI  - Sludge minimization technologies--an overview.
AB  - The management of wastewater sludge from wastewater treatment plants represents
      one of the major challenges in wastewater treatment today. The cost of the sludge
      treatment amounts to more than the cost of the liquid in many cases. Therefore
      the focus on and interest in sludge minimization is steadily increasing. In this
      paper an overview is given for sludge minimization (sludge mass reduction)
      options. It is demonstrated that sludge minimization may be a result of reduced
      production of sludge and/or disintegration processes that may take place both in
      the wastewater treatment stage and in the sludge stage. Various sludge
      disintegration technologies for sludge minimization are discussed, including
      mechanical methods (focusing on stirred ball-mill, high-pressure homogenizer,
      ultrasonic disintegrator), chemical methods (focusing on the use of ozone),
      physical methods (focusing on thermal and thermal/chemical hydrolysis) and
      biological methods (focusing on enzymatic processes).

PMID- 15259936
TI  - Partial ozonation of activated sludge to reduce excess sludge, improve
      denitrification and control scumming and bulking.
AB  - Disposal of sewage sludge is forbidden and agricultural use of stabilized sludge
      will be banned in 2005 in Switzerland. The sludge has to be dewatered, dried,
      incinerated and the ashes disposed in landfills. These processes are cost
      intensive and lead also to the loss of valuable phosphate resources incorporated
      in the sludge ash. The implementation of processes that could reduce excess
      sludge production and recycle phosphate is therefore recommended. Partial
      ozonation of the return sludge of an activated sludge system reduces
      significantly excess sludge production, improves settling properties of the
      sludge and reduces bulking and scumming. The solubilized COD will also improve
      denitrification if the treated sludge is recycled to the anoxic zone. But
      ozonation will partly inhibit and kill nitrifiers and might therefore lead to a
      decrease of the effective solid retention time of the nitrifier, which reduces
      the safety of the nitrification. This paper discusses the effect of ozonation on
      sludge reduction, the operation stability of nitrification, improvement of
      denitrification and gives also an energy and cost evaluation.

PMID- 15259937
TI  - Bacterial composition of activated sludge--importance for floc and sludge
      properties.
AB  - Activated sludge flocs consist of numerous constituents which, together with
      other factors, are responsible for floc structure and floc properties. These
      properties largely determine the sludge properties such as flocculation, settling
      and dewaterability. In this paper we briefly review the present knowledge about
      the role of bacteria in relation to floc and sludge properties, and we present a
      new approach to investigate the identity and function of the bacteria in the
      activated sludge flocs. The approach includes identification of the important
      bacteria and a characterization of their physiological and functional properties.
      It is carried out by use of culture-independent molecular biological methods
      linked with other methods to study the physiology and function, maintaining a
      single cell resolution. Using this approach it was found that floc-forming
      properties differed among the various bacterial groups, e.g. that different
      microcolony-forming bacteria had very different sensitivities to shear and that
      some of them deflocculated under anaerobic conditions. In our opinion, the
      approach to combine identity with functional analysis of the dominant bacteria in
      activated sludge by in situ methods is a very promising way to investigate
      correlations between presence of specific bacteria, and floc and sludge
      properties that are of interest.

PMID- 15259938
TI  - Sludge characterization: the role of physical consistency.
AB  - The physical consistency is an important parameter in sewage sludge
      characterization as it strongly affects almost all treatment, utilization and
      disposal operations. In addition, in many European Directives a reference to the
      physical consistency is reported as a characteristic to be evaluated for
      fulfilling the regulations' requirements. Further, in many analytical methods for
      sludge, different procedures are indicated depending on whether a sample is
      liquid or not, is solid or not. Three physical behaviours (liquid, paste-like and
      solid) can be observed with sludges, so the development of analytical procedures
      to define the boundary limit between liquid and paste-like behaviours
      (flowability) and that between solid and paste-like ones (solidity) is of growing
      interest. Several devices can be used for evaluating the flowability and solidity
      properties, but often they are costly and difficult to be operated in the field.
      Tests have been carried out to evaluate the possibility to adopt a simple
      extrusion procedure for flowability measurements, and a Vicat needle for solidity
      ones.

PMID- 15259939
TI  - The fundamentals of wastewater sludge characterization and filtration.
AB  - The move to greater emphasis on the disposal of wastewater sludges through routes
      such as incineration and the added cost of landfill emplacement puts high demands
      on dewatering technology for these sludges. A clear problem in this area is that
      wastewater sludges are slow and difficult to dewater and traditional methods of
      laboratory measurement for prediction of filtration performance are inadequate.
      This is highly problematic for the design and operational optimisation of
      centrifuges, filters and settling devices in the wastewater industry. The
      behaviour is assessed as being due to non-linear behaviour of these sludges which
      negates the use of classical approaches. These approaches utilise the linear
      portion of a t versus V2 plot (where t is the time to filtration and V is the
      specific filtrate volume) to extract a simple Darcian permeability. Without this
      parameter, a predictive capacity for dewatering using current theory is negated.

PMID- 15259940
TI  - Chemical conditioning of sludge.
AB  - With all the advances made in understanding the structure and composition of
      sewage sludges, chemical conditioning remains a trial and error process, both
      with regard to the type and dose of conditioner needed. Recent studies at
      Virginia Tech have found that biological floc consists of two types of
      biopolymer, material associated with iron and aluminium and material associated
      with calcium and magnesium. These materials behave differently when sludges
      undergo digestion. This results in very different material being released into
      solution during digestion and very different conditioning requirements. This
      study shows that the primary materials released during anaerobic digestion are
      proteins and coagulation of the colloidal protein fraction in solution is the
      primary mechanism for conditioning. For aerobically digested sludges, both
      proteins and polysaccharides make up the colloid fraction, which interferes with
      dewatering. This research also shows that the effectiveness of the digestion
      process as characterized by volatile solids destruction is directly related to
      the chemical dose required for conditioning. That is, as the solids destruction
      increases, the conditioning chemical requirement also increases. Well digested
      sludges dewater more poorly and require more conditioning chemical than those
      with less volatile solids destruction.

PMID- 15259941
TI  - Pilot study of a fluidized-pellet-bed technique for simultaneous solid/liquid
      separation and sludge thickening in a sewage treatment plant.
AB  - A fluidized-pellet-bed separator with movable sludge hoppers was applied in pilot
      scale for the separation and thickening of activated sludge mixture liquid. Under
      the condition of suspension SS around 4,000 mg/L, polymer (CJX103, cationic, MW 5
      x 10(6)) dose at a dry solid ratio of 0.003 and upward flow rate at 5.4 m/hr, the
      fluidized pellet bed performed solid/liquid separation and sludge thickening
      well. The SS concentration of the treated water was about 5 mg/L on average and
      the moisture content of the sludge after screening for 5 min was less than 94%,
      which is much lower than that after conventional settling and thickening and easy
      to be finally disposed. At a higher upward flow rate of 7.2 m/hr, similar results
      could also be obtained but higher polymer dose (solid ratio of 0.004) was
      required. The morphological characteristics and density-size relationship of the
      granular particles formed in the fluidized pellet bed were also investigated by
      image analysis and settling velocity measurement of individual particles. The two
      dimensional fractal dimension was evaluated to be 1.6-1.8, showing a good quasi
      spherical morphology of the granular particles with their density much higher
      than the conventional flocs. The results of the pilot study indicate a possible
      way to innovate the conventional secondary settling and gravitational thickening
      processes for solid/liquid separation and sludge handling, especially for small
      scale wastewater treatment plants to reach the goal of space saving and higher
      treatment efficiency.

PMID- 15259942
TI  - Improvement of anaerobic digestion of sludge.
AB  - Anaerobic digestion improvement can be accomplished by different methods. Besides
      optimization of the process conditions, pretreatment of input sludge and increase
      of process temperature is frequently used. The thermophilic process brings a
      higher solids reduction and biogas production, a high resistance to foaming, no
      problems with odour, better pathogens destruction and an improvement of the
      energy balance of the whole treatment plant. Disintegration of excess activated
      sludge in a lysate centrifuge was proved to cause increase of biogas production
      in full-scale conditions. The rapid thermal conditioning of digested sludge is an
      acceptable method of particulate matter disintegration and solubilization.

PMID- 15259943
TI  - Investigation and assessment of sludge pre-treatment processes.
AB  - The pre-treatment of sludges by disintegration will result in a number of changes
      in sludge properties. Floc destruction as well as cell disintegration will occur.
      This leads to an increase of soluble substances and fine particles. Furthermore,
      biochemical reactions may appear during or immediately after disintegration. The
      influence of disintegration of excess sludge on anaerobic digestion was studied
      in full scale. A stirred ball mill, an ultrasound disintegrator, a lysate
      centrifuge and ozone treatment were used. The results of the degradation process
      were compared to a reference system without pre-treatment. An enhancement of the
      degree of degradation of 7.4% to 20% was observed. The pollution of sludge water
      as well as the dewatering properties of the digested sludge were investigated.
      COD and ammonia in the sludge water were increased and a higher polymer demand
      was observed while the solid content after dewatering stayed almost unchanged.
      Based on these results the cost effectiveness has been assessed taking into
      account different conditions (size of WWTP, cost for disposal, etc.). Capital and
      energy costs are the main factors while the decrease in disposal costs due to the
      reduced amount of sludge is the main profit factor.

PMID- 15259944
TI  - Process performance and change in sludge characteristics during anaerobic
      digestion of sewage sludge with ozonation.
AB  - A new process configuration combining anaerobic digestion with ozonation, and
      operated at long SRT, was studied with the objective of on-site reduction in
      sludge quantity and improving biogas recovery. The process performance with
      respect to solid reduction efficiency and other important process parameters like
      accumulation of inorganic solids, changes in sludge viscosity and dewatering
      characteristics were evaluated from the data of long term pilot scale continuous
      experiments conducted using a mixture of primary and secondary municipal sewage
      sludge. Due to sludge ozonation and long SRT, high VSS degradation efficiency of
      approximately 80% was achieved at a reactor solid concentration of 6.5%. A high
      fraction of inorganic solid (>50%) consisting mainly of acid insoluble and iron
      compounds was found to accumulate in the reactor. The high inorganic content
      accumulated in the digested sludge did not, however, contribute to the observed
      increase in sludge viscosity at high solid concentration. The sludge viscosity
      was largely found to depend on the organic solid concentration rather than the
      total solid content. Moreover, higher inorganic content in the digested sludge
      resulted in better sludge dewaterability. For a quick assessment of the economic
      feasibility of the new process, an economic index based on the unit cost of
      digested sludge disposal to unit electric cost is proposed.

PMID- 15259945
TI  - Anaerobic bioprocessing of sewage sludge, focusing on degradation of linear
      alkylbenzene sulfonates (LAS).
AB  - Anaerobic degradation of sludge amended with linear alkylbenzene sulfonates (LAS)
      was tested in a one stage continuous stirred tank reactor (CSTR) and a two stage
      reactor system consisting of a CSTR as first step and upflow anaerobic sludge bed
      (UASB) reactor as the second step. Anaerobic removal of LAS was only observed at
      the second step but not at the first step. Removal of LAS in the UASB reactors
      was approx. 80% where half was due to absorption and the other half was
      apparently due to biological removal as shown from the LAS mass balance. At the
      end of the experiment the reactors were spiked with 14C-LAS which resulted in
      5.6% 14CO2 in the produced gas. Total mass balance of the radioactivity was
      however not achieved. In batch experiments it was found that LAS at
      concentrations higher than 50 mg/l is inhibitory for most microbial groups of the
      anaerobic process. Therefore, low initial LAS concentration is a prerequisite for
      successful LAS degradation. The results from the present study suggest that
      anaerobic degradation of LAS is possible in UASB reactors when the concentration
      of LAS is low enough to avoid inhibition of microorganisms active in the
      anaerobic process.

PMID- 15259946
TI  - Sludge pre-treatment with pulsed electric fields.
AB  - The anaerobic stabilization process depends - among other things - on the bio
      availability of organic carbon. Through pre-treatment of the sludge which leads
      to the destruction of micro-organisms and to the setting-free of cell content
      substances (disintegration), the carbon can be microbially converted better and
      faster. Moreover, effects on the digestion are likely. However, only little
      experience is available in sludge treatment with pulsed electric fields.
      Laboratory-scale digestion tests have been run to analyse the influence of pulsed
      electric fields on the properties of sludge, anaerobic degradation, sludge water
      reload and foaming of digesters. The results will be compared with those of other
      disintegration methods (high pressure homogeniser, thermal treatment). The effect
      of pre-treatment on the sludge is shown by the COD release. Degrees of
      disintegration have been achieved up to 20%. The specific energy input was high.
      The energy consumption has been decreased by initial improvements (pre-heating to
      55 degrees C). The filament bacteria were partially destroyed. The foam reduction
      in the digesters was marginal. The anaerobic degradation performance has been
      improved in every case. The degradation rate of organic matter increased about
      9%. Due to the increase of degradation, there is a higher reload of the sludge
      water with COD and nitrogen compounds.

PMID- 15259947
TI  - Production of class A biosolids with anoxic low dose alkaline treatment and odor
      management.
AB  - The feasibility of full-scale anoxic disinfection of dewatered and digested
      sludge from Winnipeg, Manitoba with low lime doses and lagoon fly ash was
      investigated to determine if a class A product could be produced. Lime doses of
      50 g, 100 g, and 200 g per kg of biosolids (dry) were used along with fly ash
      doses of 500 g, 1,000 g, and 1,500 g per kg of biosolids (dry). The mixed product
      was buried in eight-10 cubic metre trenches at the West End Water Pollution
      Control Center in Winnipeg. The trenches were backfilled with dirt and trapped to
      simulate anoxic conditions. Sampling cages were packed with the mixed product and
      pathogens non-indigenous to Winnipeg's biosolids. The cages were buried amongst
      the mixed biosolids in the trench. The non-indigenous pathogens spiked in the
      laboratory were the helminth Ascaris suum and the enteric virus reovirus. Samples
      were removed at days 12, 40, 69, 291, and 356 and were tested for the presence of
      fecal Coliform, Clostridium perfringens spores, Ascaris suum eggs, and reovirus.
      The pH, total solids, and free ammonia content of the mixed product were also
      determined for each sample. Odor was quantified for samples at both 291 and 356
      days. Fecal Coliform bacteria and reovirus were completely inactivated for doses
      as low as 100 g lime per kg biosolids (dry) and 50 g lime + 500 g fly ash per kg
      biosolids (dry). Spores of the bacteria C. perfringens experienced a 4-log
      reduction when treated with 100 g lime per kg biosolids and a 5-log reduction
      when treated with doses as low as 50 g lime + 500 g fly ash per kg biosolids
      (dry) after 69 days. Ascaris eggs were completely inactivated in 5 gram packets
      for all treatments involving 100 g lime per kg biosolids (dry) after 69 days.
      Class A pathogen requirements were met for all treatments involving a lime dose
      of at least 100 g per kg biosolids. The odor potential from the produced
      biosolids is also assessed.

PMID- 15259948
TI  - Full scale validation of helminth ova (Ascaris suum) inactivation by different
      sludge treatment processes.
AB  - The Norwegian sewage sludge regulation requires disinfection (hygienisation) of
      all sludges for land application, and one of the criteria is that disinfected
      sludge should not contain viable helminth ova. All disinfection processes have to
      be designed and operated in order to comply with this criterion, and four
      processes employed in Norway (thermophilic aerobic pre-treatment, pre
      pasteurisation, thermal vacuum drying in membrane filter presses and lime
      treatment) have been tested in full scale by inserting semipermeable bags of
      Ascaris suum eggs into the processes for certain times. For lime treatment
      supplementary laboratory tests have been conducted. The paper presents the
      results of the experiments, and it could be concluded that all processes, except
      lime treatment, could be operated at less stringent time-temperature regimes than
      commonly experienced at Norwegian plants today.

PMID- 15259949
TI  - Biotechnology of intensive aerobic conversion of sewage sludge and food waste
      into fertilizer.
AB  - Biotechnology for intensive aerobic bioconversion of sewage sludge and food waste
      into fertilizer was developed. The wastes were treated in a closed reactor under
      controlled aeration, stirring, pH, and temperature at 60 degrees C, after
      addition of starter bacterial culture Bacillus thermoamylovorans. The
      biodegradation of sewage sludge was studied by decrease of volatile solids (VS),
      content of organic carbon and autofluorescence of coenzyme F420. The degradation
      of anaerobic biomass was faster than biodegradation of total organic matter. The
      best fertilizer was obtained when sewage sludge was thermally pre-treated, mixed
      with food waste, chalk, and artificial bulking agent. The content of volatile
      solid and the content of organic carbon decreased at 24.8% and 13.5% of total
      solids, respectively, during ten days of bioconversion. The fertilizer was a
      powder with moisture content of 5%. It was stable, and not toxic for the
      germination of plant seeds. Addition of 1.0 to 1.5% of this fertilizer to the
      subsoil increased the growth of different plants tested by 113 to 164%. The
      biotechnology can be applied in larger scale for the recycling of sewage sludge
      and food wastes in Singapore.

PMID- 15259950
TI  - Integrated, long term, sustainable, cost effective biosolids management at a
      large Canadian wastewater treatment facility.
AB  - The Greater Moncton Sewerage Commission's 115,000 m3/d advanced, chemically
      assisted primary wastewater treatment facility located in New Brunswick, Canada,
      has developed an integrated, long term, sustainable, cost effective programme for
      the management and beneficial utilization of biosolids from lime stabilized raw
      sludge. The paper overviews biosolids production, lime stabilization, conveyance,
      and odour control followed by an indepth discussion of the wastewater sludge as a
      resource programme, namely: composting, mine site reclamation, landfill cover,
      land application for agricultural use, tree farming, sod farm base as a soil
      enrichment, topsoil manufacturing. The paper also addresses the issues of metals,
      pathogens, organic compounds, the quality control program along with the
      regulatory requirements. Biosolids capital and operating costs are presented.
      Research results on removal of metals from primary sludge using a unique
      biological process known as BIOSOL as developed by the University of Toronto,
      Canada to remove metals and destroy pathogens are presented. The paper also
      discusses an ongoing cooperative research project with the Universite de Moncton
      where various mixtures of plant biosolids are composted with low quality soil.
      Integration, approach to sustainability and "cumulative effects" as part of the
      overall biosolids management strategy are also discussed.

PMID- 15259951
TI  - Digestion of sludge and organic waste in the sustainability concept for Malmo,
      Sweden.
AB  - Anaerobic digestion of sludge has been part of the treatment plant in Malmo for
      many years and several projects on optimisation of the digestion process have
      been undertaken in full scale as well as in pilot scale. In order to facilitate a
      more sustainable solution in the future for waste management, solid waste organic
      waste is sorted out from households for anaerobic treatment in a newly built city
      district. The system for treatment of the waste is integrated in a centralised
      solution located at the existing wastewater treatment plant. A new extension of
      the digester capacity enables separate as well as co-digestion of sludge together
      with urban organic waste from households, industry, restaurants, big kitchens,
      food stores, supermarkets, green markets etc. for biogas production and
      production of fertiliser. Collection and pre-treatment of different types of
      waste are in progress together with examination of biogas potential for different
      types of organic waste. Collection of household waste as well as anaerobic
      digestion in laboratory and pilot scale has been performed during the last year.
      It is demonstrated that organic household waste can be digested separately or in
      combination with sludge. In the latter case a higher biogas yield is found than
      should be expected from digestion of the two materials separately. Household
      waste from a system based on collection of organic waste from grinders could be
      digested at mesophilic conditions whereas digestion failed at thermophilic
      conditions.

PMID- 15259952
TI  - Characterization and evaluation of potential reuse options for wastewater sludge
      and combined sewer system sediments in Mexico.
AB  - Combined sewer systems generate sediments that have characteristics similar to
      those of primary sludge. Mexico City has such a system composed of a network of
      pipes, regulation structures (dams, basins) and open channels. The annual
      generation of sediments is estimated at 2.8 Mm3, which includes 0.41 Mm3 of
      sludge. As a result, the total capacity for transporting water is reduced
      considerably, making it necessary to extract yearly an approximate 0.85 Mm3 of
      those materials and to send them to a final disposal site with a capacity that is
      being exhausted. As part of the local Governmental effort, this project evaluates
      the quality of sediments from 6 dams, 4 regulation basins, 2 open channels, and 3
      transfer stations. Also, sludge from 20 wastewater treatment plants was sampled.
      The results showed an important presence of lead and hydrocarbons in some
      sediments, and some sludge samples contained arsenic and nickel above the limits.
      Moreover, microbial levels exceeded the limits in all the sediments and sludge
      samples. Erosion was linked to the generation of an important amount of sediments
      based on lead concentration. A classification was established to determine the
      degree of contamination of the sediments as well as the required treatment to
      allow their potential reuse.

PMID- 15259953
TI  - The influence of operating experiences in the design of the IVAR thermal drying
      plant expansion in Stavanger, Norway.
AB  - The Regional Wastewater Treatment Plant of North Jaeren (IVAR IKS) serves the
      Stavanger conurbation with a population equivalence of 240,000. The site was the
      first in Norway to operate a thermal drying and a pelletising plant for municipal
      sludge. Since the start up in 1992, IVAR has encountered most of the operational
      problems typically associated with thermal drying processes. Considerable
      modifications have been made and lessons learnt resulting in the plant being one
      of the few thermal drying facilities in Norway which continues to operate
      successfully. In general, thermal drying is often considered as a costly, energy
      demanding and complex process requiring careful attention to safety aspects such
      as risks of self-combustion, fires and dust explosions. The paper presents
      general considerations of operating experiences influencing the procurement and
      design stage of the new extended IVAR thermal drying plant. Furthermore, topical
      issues important for resolution of thermal drying problems are also discussed.
      Mass and energy balances for the Stavanger plant are presented.

PMID- 15259954
TI  - Phosphorus recovery--an overview of potentials and possibilities.
AB  - The endeavour towards a sustainable society has led to an interest in the
      recovery and recirculation or reuse of phosphorus from wastewater among
      environmentalists and politicians. In a recent interdisciplinary investigation
      commissioned by the Swedish Environmental Protection Agency, an attempt was made
      to evaluate different possibilities to recover phosphorus from wastewater or its
      fractions; systems based on source separation of urine or of combined toilet
      wastes, on the extraction of phosphorus from sludge, from ashes after
      incineration of sludge or from wastewater as well as the direct recirculation of
      hygienised digested and dewatered sludge were studied. Aspects like technology,
      environmental effects, resource economy, economy, markets, organisational aspects
      and user aspects were studied. In this overview the potential and possibility to
      recover and recirculate phosphorus from wastewater is discussed, mainly based on
      the findings in this investigation.

PMID- 15259955
TI  - Dutch analysis for P-recovery from municipal wastewater.
AB  - There is a considerable practical interest in phosphorus recovery from water
      authorities, elementary P-industry, fertilizer industry and regulators in a
      number of countries. Due to a handful of full-scale plants worldwide, P-recovery
      can be seen as technically feasible. However, the economic feasibility of P
      recovery from sewage can still be judged as dubious. The most important reason
      for this is that the prices of the techniques (in euro/tonne P) are much higher
      compared to the prices of phosphate rock. In this paper an analysis is given to
      recover phosphate from municipal wastewater for the elementary P-industry
      Thermphos International B.V. and the fertiliser industry Amsterdam Fertilizers
      B.V. in The Netherlands. Several scenarios are evaluated and the end products of
      these scenarios are compared to the quality required by both industries. From a
      Dutch study it became clear that all end products from the final sludge treatment
      do not provide a good source of secondary phosphate. As a consequence of this,
      the most preferred possibility for P-recovery is to extract phosphate before
      sludge goes to the final sludge treatment. Different scenarios can be selected
      based on the position of P-recovery in the WWTP configuration, the type of P
      recovery product, and the precipitation technique. Local conditions will
      determine which scenario is the most expedient. Because it is more realistic to
      judge a practical situation instead of theoretical estimations based on
      literature, some local situations have to be assessed in sufficient detail to
      gain more feeling for the expenses and possible savings of P-recovery. One
      important actor that should be involved in the process management around P
      recovery, is the national government. Especially, the Government have the
      responsibility for sustainable development and should have attention for some
      stimulation of P-recovery in The Netherlands. Water authorities and the P- and
      fertilizer industry made already some good steps.

PMID- 15259956
TI  - Direct energy recovery from primary and secondary sludges by supercritical water
      oxidation.
AB  - Supercritical water oxidation (SCWO) oxidizes organic and biological materials
      virtually completely to benign products without the need for stack gas scrubbing.
      Heavy metals are recovered as stabilized solid, along with the sand and clay that
      is present in the feed. The technology has been under development for twenty
      years. The major obstacle to commercialization has been developing reactors that
      are not clogged by inorganic solid deposits. That problem has been solved by
      using tubular reactors with fluid velocities that are high enough to keep solids
      in suspension. Recently, system designs have been created that reduce the cost of
      processing sewage sludges below that of incineration. At 10 wt- % dry solids,
      sludge can be oxidized with virtually complete recovery of the sludge heating
      value as hot water or high-pressure steam. Liquid carbon dioxide of high purity
      can be recovered from the gaseous effluent and excess oxygen can be recovered for
      recycle. The net effect is to reduce the stack to a harmless vent with minimal
      flow rate of a clean gas. Complete simulations have been developed using physical
      property models that accurately simulate the thermodynamic properties of sub- and
      supercritical water in mixtures with O2, N2, CO2, and organics. Capital and
      operating cost estimates are given for sewage sludge treatment, which are less
      costly than incineration. The scenario of direct recovery of energy from sludges
      has inherent benefits compared to other gasification or liquefaction options.

PMID- 15259957
TI  - Sludge thermal oxidation processes: mineral recycling, energy impact, and
      greenhouse effect gases release.
AB  - Different treatment routes have been studied for a mixed sludge: the conventional
      agricultural use is compared with the thermal oxidation processes, including
      incineration (in gaseous phase) and wet air oxidation (in liquid phase). The
      interest of a sludge digestion prior to the final treatment has been also
      considered according to the two major criteria, which are the fossil energy
      utilisation and the greenhouse effect gases (CO2, CH4, N2O) release. Thermal
      energy has to be recovered on thermal processes to make these processes
      environmentally friendly, otherwise their main interest is to extract or destroy
      micropollutants and pathogens from the carbon cycle. In case of continuous energy
      recovery, incineration can produce more energy than it consumes. Digestion is
      especially interesting for agriculture: according to these two schemes, the
      energy final balance can also be in excess. As to wet air oxidation, it is
      probably one of the best ways to minimize greenhouse effect gases emission.

PMID- 15259958
TI  - Experience and lessons learned from sewage sludge pyrolysis in Australia.
AB  - Management of sewage sludge via "publicly acceptable" methods is becoming
      increasingly difficult, primarily due to health and environmental concerns with
      respect to reuse of the product in agriculture. Consequently thermal processes
      are gaining popularity with significantly increased interest being shown in
      pyrolysis and gasification processes, due to their "non-incineration status". One
      such process is the ENERSLUDGE technology which has been developed and
      commercialised by Environmental Solutions International Ltd (ESI). The world's
      first commercial ENERSLUDGE plant is located at the Subiaco Wastewater Treatment
      Plant (WWTP) that was handed over to the client, the Water Corporation of Western
      Australia in June 2001. Extensive design knowledge and operational experience has
      now been accumulated from this commercial pyrolysis facility and future
      applications of the technology will benefit immensely from the lessons learned
      and experience gained from this facility.

PMID- 15259959
TI  - Utilization of sludge in building material.
AB  - Several thermal solidification processes have been developed mainly in Japan.
      They are lightweight aggregates, brick, interlocking tile, char, and slag. A full
      scale plant of them has been successfully operated for more than 10 years. The
      quality of the end products is better than the traditional ones. They are all
      substitutive to existing ones. The Japanese experience proves that all the
      processes are technically feasible, but not economically. Their manufacturing
      cost is always higher than market price. In addition, they consume large amounts
      of energy. However, if they are identified for a process of sludge disposal, all
      of them are worth considering for a big city where there is no place for the
      sludge to go. The end products can be reused inside the city. A new alternative
      is "Portland cement". A Portland cement manufacturer accepts sewage sludge, if
      being paid some amount of money. An average payment is US$100 each 1,000 kg of
      ash or sludge cake. The Portland cement manufacturer accepts either cake or ash
      at the same price. It is about 50 to 30% of the energy cost of thermal
      solidification. The question is which is the better, dewatered cake or
      incinerated ash, for the Portland cement application. The answer is "it depends
      on the distance between the sewage plant and the Portland cement plant."

PMID- 15259960
TI  - Recycling of sludge with the Aqua Reci process.
AB  - Supercritical Water Oxidation (SCWO) is an innovative and effective destruction
      method for organics in sewage sludge. The SCWO process leaves a slurry of
      inorganic ash in a pure water phase free from organic contaminants, which opens
      possibilities for a simple process to recover components like phosphates and/or
      coagulants from the sewage sludge, a process marketed as the Aqua Reci. In a
      continuous pilot plant for the SCWO process digested sludge has been treated. The
      ash has been extracted in lab- and pilot scale with both caustic and acids in
      order to recover phosphates and coagulants. The particle size of the inorganic
      contaminants in the water after the SCWO process is between 1-10 microm, which
      means that it is very reactive. The phosphate, and partly the aluminium, can be
      extracted with caustic as iron and heavy metals are completely insoluble in
      caustic. This is a method to separate the phosphates from the rest of the
      contaminants. However, high calcium content will bind the phosphate as calcium
      phosphate insoluble in caustic. In most cases the calcium content is too high and
      the best solution is to dissolve phosphates and all metals with sulphuric acid.
      From this solution first iron phosphate can be separated and thereafter in a
      second step aluminium and finally heavy metals in a third step. Iron can be
      separated from the phosphate, either by leaching the phosphate with caustic off
      to sodium phosphate leaving a precipitate consisting of iron hydroxide, or the
      iron phosphate can be dissolved in hydrochloric acid followed by a liquid
      extraction process where ferric chloride can be separated leaving a phosphoric
      acid. By the acid dissolving process it is possible to recover phosphate, iron,
      aluminium, and heavy metals from the inorganic since the Aqua Reci process only
      leaves a silica residue representing about 10% of the DS content in the original
      sludge.

PMID- 15259961
TI  - Sustainable biosolids--welcomed practice through community partnership and the
      consequential economic benefits.
AB  - Technically, most people agree that conserving soil organic matter and completing
      nutrient cycles by applying animal manures, treated organic wastes and biosolids
      to land is the most sustainable option in the majority of situations. It is also
      generally the least expensive. There has been a huge amount of research into the
      hazards, and this has concluded that the risks can be managed to acceptable
      levels. But there has been insufficient attention to communicating this
      knowledge, as so often in the scientific and technological arena. Perception is
      reality. Nowadays compliance with regulations (whilst essential) is not enough;
      public and stakeholder attitudes can be of decisive importance. Sometimes policy
      makers speculate what public attitudes might be without really asking them. This
      paper will describe an initiative to create a partnership open to anybody with an
      interest in the use of organic materials on land to develop consensus on good
      practice and to share knowledge. It summarises an attitude survey of more than
      140 organisations, which was then debated at a workshop in July 2002. The
      conclusion from this study was that all parties considered a partnership is
      essential to share knowledge, build mutual trust and agree practices that are
      welcomed by all in the food chain. The paper will describe the steps to
      establishing a partnership organisation, its aims and objectives, the work to
      date and the plans for the future. The Environment Agency considers this very
      important and has largely funded the work to date. The consequences of failing to
      establish welcomed practices would be loss of the facility to use organic
      resources on land.

PMID- 15259962
TI  - Sustainable sludge management in developing countries.
AB  - Worldwide, unsanitary conditions are responsible for more than three million
      deaths annually. One of the reasons is the low level of sanitation in developing
      countries. Particularly, sludge from these regions has a high parasite
      concentration and low heavy metal content even though the available information
      is limited. Different issues needed to achieve a sustainable sludge management in
      developing nations are analysed. Based on this analysis some conclusions arise:
      sludge management plays an important role in sanitation programs by helping
      reduce health problems and associated risks; investments in sanitation should
      consider sludge management within the overall projects; the main restriction for
      reusing sludge is the high microbial concentration, which requires a science
      based decision on the treatment process, while heavy metals are generally low;
      adequate sludge management needs the commitment of those sectors involved in the
      development and enforcement of the regulations as well as those that are directly
      related to its generation, treatment, reuse or disposal; current regulations have
      followed different approaches, based mainly on local conditions, but they favour
      sludge reuse to fight problems like soil degradation, reduced crop production,
      and the increased use of inorganic fertilizers. This paper summarises an overview
      of these issues.

PMID- 15259964
TI  - Why do we resist change?

PMID- 15259963
TI  - Route to synthesize the sludge management processes.
AB  - A route for the synthesis of the treatment train of sewage sludge is proposed,
      and the conceptual design stage is demonstrated, using local sludge as an
      example.

PMID- 15259965
TI  - Migration following crown-lengthening procedure--a case report.
AB  - Periodontal surgery may be accompanied with some postoperative complications such
      as pain, swelling and sloughing, purulence or infection, transient bacteremia,
      nerve trauma, and hemorrhage. In general, a resective surgical intervention may
      implicate reduction in the attachment apparatus. Migration as a postoperative
      complication has never been addressed in the literature. This paper presents a
      case report detailing migration of a tooth, following a surgical preprosthetic
      clinical crown-lengthening procedure, which was repositioned using adjunctive
      orthodontics with a removable maxillary modified Hawley appliance. It is
      incumbent upon the dentist to examine meticulously the occlusal status of the
      teeth prior to a planned surgical intervention and to take measures preventing
      any possible tooth migration during the healing process. Failure to achieve
      occlusal and intra-arch stability may lead to undesired tooth movement in the
      arch postsurgery, affecting future prognosis and complicating any planned
      prosthetic work.

PMID- 15259966
TI  - Accuracy of a robotic system for the reproduction of condylar movements: a
      preliminary report.
AB  - OBJECTIVE: Methods in restorative dentistry have to meet stringent accuracy
      requirements. The accuracy of robotic systems used for the reproduction of
      condylar movements has not been determined. The purpose of this study was to
      assess the accuracy of the robot system, ROSY, a robotlike electronic simulator
      (developed by the author) that reproduces condylar movements previously recorded
      on a patient. METHOD AND MATERIALS: The simulator consists of a custom-designed
      ultrasonic system that records mandibular movements in all three dimensions
      (vertical, horizontal, and coronal) with six degrees of freedom. The simulator
      automatically reproduces all movements around these axes with a robotic system
      with six stepper motors. The accuracy of the simulator was measured for all
      directions in space by registering eccentric jaw positions on both sides of 10
      subjects in two ways: (1) by the ultrasound registration system; and (2)
      simultaneously with an interocclusal recording medium. The standard deviation and
      interquartile range of the differences between the measurements based on these
      two approaches were used to statistically describe the accuracy of ROSY. RESULTS:
      The accuracy of the entire system was better than 0.28 mm. CONCLUSION: The
      electronic simulator comes with an accuracy that may render it suitable for
      clinical applications.

PMID- 15259967
TI  - Clinical application of a new cone-beam computerized tomography system to assess
      multiple two-dimensional images for the preoperative treatment planning of
      maxillary implants: case reports.
AB  - Accurate assessment of the location of the maxillary sinuses, incisive canal, and
      nasal cavity, as well as the height, width, and angulation of bone is essential
      for implant treatment planning. The purpose of this study was to introduce the
      clinical application of a cone-beam computerized tomography system (Ortho-CT) to
      assess multiple two-dimensional (2D) images for the preoperative treatment
      planning of maxillary implants. To evaluate the multiple 2D images scanned using
      the Ortho-CT system the maxillary region placed with radiopaque template in the
      maxilla. Ortho-CT images provided useful information for evaluating the
      morphology of the maxilla, for locating the incisive canal, maxillary sinuses,
      nasal cavity, and for showing the relationship of the template to the bone. It is
      concluded that the Ortho-CT system is a useful aid for diagnosis and treatment
      planning for maxillary implant treatment.

PMID- 15259968
TI  - Resin bonding to sclerotic, noncarious, cervical lesions.
AB  - Noncarious, cervical, wedge-shaped, sclerotic lesions are commonly encountered in
      clinical practice. In such lesions, dentin has been pathologically altered, often
      resulting in partial or complete obliteration of the dentinal tubules. These
      lesions are known to respond to etching and bonding differently from normal
      dentin, leading to complications during clinical treatment. A search of the
      literature was performed to obtain background information on the most commonly
      cited etiologic factors, clinical diagnoses, and morphologic and chemical
      characterizations along with an extensive review of all potential obstacles to
      bonding the most recent adhesives to such a dentinal substrate. Recent progress
      in adaptive strategies to render dentin more receptive to resin bonding is
      emphasized in this article, and the major drawbacks of these strategies are
      discussed.

PMID- 15259969
TI  - An in vitro study of dentin exposure during resin-bonded fixed partial denture
      preparation.
AB  - OBJECTIVES: The aim of this in vitro study was to investigate whether dentin is
      exposed during tooth preparation for resin-bonded fixed partial dentures and, if
      so, to quantify the amount of dentin exposure. METHOD AND MATERIALS: Twenty
      extracted premolars were prepared in the following manner: The palatolingual and
      proximal axial surfaces were reduced by 0.50 mm. Mesial and distal grooves, 1.00
      mm in depth, and mesial and distal occlusal rest seats, measuring 2.00 mm
      buccolingually x 1.50 mm mesiodistally x 1.00 mm deep, were prepared. The
      specimens were stained with a modified van Gieson's stain to identify dentin
      exposure, mounted on a jig to allow standardization, and photographed after 30
      degree rotation to create a panoramic image of each tooth. The image was modified
      and analyzed to measure the percentage of the preparation area that exhibited
      dentin exposure. RESULTS: Dentin exposure was noted in all specimens. The mean
      area of dentin exposure was 11.06 mm2 (16.15% of the preparation area). The
      minimum and maximum areas of dentin exposure were 4.07 mm2 (7.03%) and 19.73 mm2
      (27.28%), respectively. CONCLUSION: Dentin is exposed during resin-bonded fixed
      partial denture preparation if current tooth preparation guidelines are followed,
      despite the commonly made recommendation that the preparation remain within
      enamel. The region of the grooves consistently exhibited exposed dentin; exposure
      at the cervical margin was variable.

PMID- 15259970
TI  - Natural tooth pontic fixed partial denture using resin composite-reinforced glass
      fibers.
AB  - This article describes the rationale and method of using glass fibers reinforced
      with resin composite as an external framework to reuse a patient's own natural
      anterior tooth as a pontic, after extraction.

PMID- 15259971
TI  - Prevalence of fused and geminated teeth in Jordanian adults.
AB  - OBJECTIVES: The purpose of this study was to address the prevalence of dental
      fusion and gemination in a sample of Jordanian dental patients. Frequency
      distributions of these conditions among different types of teeth are also
      presented. METHOD AND MATERIALS: The data were collected from examination of
      radiographs from a random sample of periapical films. In all, 9,373 teeth from
      1,660 dental records at the Faculty of Dentistry, Irbid, Jordan, were evaluated.
      A tooth was recorded having gemination if its crown was enlarged with a normal
      root and the tooth count was normal. A tooth was recorded fused if the tooth
      crown and root were enlarged and the tooth count revealed a missing tooth.
      RESULTS: Fusion and gemination were detected in 18 and 21 teeth, respectively,
      with prevalence of 0.19% and 0.22%, respectively. Therefore, double teeth were
      found in 39 teeth with a prevalence of 0.42%. Maxillary central incisors Were the
      most commonly affected (3.6%), followed by mandibular third molars (0.9%).
      CONCLUSION: Fusion and gemination are uncommon conditions, but they are important
      dental anomalies that could affect any tooth in the mouth. Recognizing the
      condition will facilitate the endodontic, prosthodontic, periodontic,
      orthodontic, and surgical clinical management of such teeth.

PMID- 15259972
TI  - In vitro evaluation of pH changes induced by calcium hydroxide liners.
AB  - OBJECTIVES: Since the highly alkaline pH of calcium hydroxide is considered by
      many to be responsible for its biologic activity, the possible variations of pH
      induced by the different calcium hydroxide liners are accepted as a major
      concern. The aim of the present study was to determine the pH changes of five
      different calcium hydroxide liners and variations of pH levels at different time
      intervals. METHOD AND MATERIALS: The materials tested were Dycal, Life, Calic,
      Dycal VLC, and Calcident 450. Samples were prepared according to manufacturer
      instructions and by using plastic molds; five standard samples from each material
      were prepared. The samples were then placed in separate vials, containing 10 mL
      deionized water (pH 7.0), and stored at room temperature (200C). The pH
      measurements were taken 1 hour, 24 hours, 3 days, and 7 days after mixing. The pH
      variations of each material at the given time intervals were recorded, and the
      means were calculated. RESULTS: Statistical analysis showed significantly high
      differences between the mean pH values induced by each material at all time
      intervals. The highest value for the first-hour measurement was for Dycal VLC,
      and the highest values for the other time intervals were for Calcident 450. The
      pH values of the materials exhibited statistically significant differences among
      all the time intervals. CONCLUSION: All materials changed the pH of deionized
      water toward alkaline.

PMID- 15259973
TI  - Survey of the effectiveness of masking noises during dental treatment--a pilot
      study.
AB  - OBJECTIVE: The aim of this study was to test the effectiveness of a newly
      developed system, using masking noises with specific frequencies and amplitudes,
      adjusted to typical noises experienced during dental treatment such as the high
      speed hand-held drill. METHOD AND MATERIALS: In accordance with an analysis of
      typical noises experienced during dental treatment, masking noises with specific
      frequencies (frequency range 0.02 to 20 kHz) and amplitudes were created, with
      the aim of reducing the patients' awareness of typical treatment noises by
      overlaying frequencies. Two hundred fifty-four outpatients (113 males, 141
      females) with a mean age of 32 years (+/- 10.5 years) were enrolled in this
      study. Patients were treated 15 minutes with and 15 minutes without the masking
      noise. Patients and practitioners filled out questionnaires aimed to evaluate the
      effectiveness of the system, sensitivity to noise (scale 0 to 10; 0 = effective,
      10 = noneffective), psychologic aspects, and statements of fear. RESULTS: There
      was a significant reduction in patients' awareness of noise using this system
      during dental treatment. Most of the patients regarded the masking noise as a
      pleasureable supplementation to common treatment and would select this manner of
      dental treatment employing the device again (81.5%); 48.2% said they were more
      relaxed. The system does not, in principle, interfere with dental treatment, and
      in most instances, the device does not impede the communication between
      practitioners and patients. CONCLUSION: The present study demonstrates that using
      masking noises during dental treatment reduces the sensitivity to drill noise,
      reduces fear and stress, and may be useful in dental practice as an adjunct to
      common dental treatment.

PMID- 15259974
TI  - Naso-orbicular tissue necrosis by Streptococcus parasanguis in a patient with
      Fanconi anemia: clinical and laboratory aspects.
AB  - Fanconi anemia (FA) is a rare autosomal recessive disorder, characterized by
      pancytopenia and progressive hypoplasia of the bone marrow. A 23-year-old woman
      with FA showed severe pancytopenia and developed an abscess on the infraorbicular
      region on the right side of the face that progressed to phlegmon and caused
      tissue necrosis of the nostrils, nasal septum, nasal fossa, and posterior orbital
      region. Laboratory examination showed Streptococcus parasanguis as the etiologic
      agent of the phlegmon. Supportive treatment was recommended due to donor
      incompatibility for bone marrow transplant. The intraoral examination showed
      spontaneous gingival bleeding, edema of the interdental papillae, hematomas on
      the superior and inferior lips, bacterial and fungal infections, and adequate
      oral hygiene. The patient was treated with the administration of an antibiotic
      (imipenem), an antifungal (amphotericin B), and mouth washing with antiseptic
      solutions. Periodontal prophylaxis and orientation to and control of oral hygiene
      and diet were also used during the remission period. For functional and esthetic
      rehabilitation of the alar regions and nasal dorsum, an acrylic resin nasal
      prosthesis was made, supported by a spectacle frame.

PMID- 15259975
TI  - A retrospective study of 60 cases of salivary gland tumors in a Thai population.
AB  - Sixty cases of salivary gland tumors were diagnosed in the Oral Pathology
      Department, Faculty of Dentistry, Mahidol University, Bangkok, Thailand, from
      1973 to 2002. Fifty-two cases (86.7%) involved the intraoral minor salivary
      glands, six cases (10%) were found in the major glands, and two cases (3.3%) were
      intrabony. The predominance of malignant over benign tumors was evident with
      68.3% being malignant and 31.7% benign. Patients ranged in age from 9 to 75
      years. The female to male ratio of benign intraoral salivary gland tumors was 1.4
      to 1 and of malignant types was 1.1 to 1. The principle site of occurrence was
      the palate (65.4%), followed by buccal mucosa (13.5%). Pleomorphic adenoma (30%)
      was the most common benign tumor, and mucoepidermoid carcinoma (44.3%) was the
      most common malignant tumor. Comparing the data from the present study with other
      series, some discrepancies exist.

PMID- 15259976
TI  - Severe hypodontia and asymptomatic bilaterally ectopic impacted teeth in the
      coronoid processes: a case report.
AB  - An asymptomatic case in which severe hypodontia and mandibular ectopic impacted
      teeth in the coronoid processes are visualized through panoramic radiographs, is
      presented.

PMID- 15259977
TI  - The role of lipoid proteinosis in gingival hypertrophy.
AB  - Hyalinosis cutis et mucosae (lipoid proteinosis, Urbach-Wiethe disease) is a rare
      syndrome with autosomal recessive inheritance. The disease is characterized by
      diffuse deposition of a hyalinelike substance in the dermis, submucosal
      connective tissue, and various internal organs. In this study, the patient
      demonstrated classic signs and symptoms of lipoid proteinosis except for gingival
      infiltration. Gingival infiltration is still an unexplainable feature of this
      disease. In the context of this case, the diagnostic significance of the
      microscopic findings of the gingival tissues and the possible factors playing a
      role in gingival hypertrophy, are discussed.

PMID- 15259978
TI  - Idiopathic osteosclerosis (enostosis, dense bone silands, focal periapical
      osteopetrosis).

PMID- 15259979
TI  - [Preliminary linkage analysis on autosomal dominant microphthalmia with 12
      microsatellite markers].
AB  - In this preliminary study a Chinese autosomal dominant microphthalmia family were
      investigated and the linkage analyses were performed with six previously reported
      loci (CHX10, MITF, RX, MCOP, NNO1, NNO2) and six microsatellite markers on
      chromosome 11 as well. The allelic polymorphisms of those microsatellite markers
      were identified by using polymerase chain reaction, polyacrylamide gel
      electrophoresis and silver-staining techniques. The LOD scores between
      microsatellite markers and the disease were obtained by using MLINK software. Our
      results showed that the linkage between the microphthalmia in this family with
      the 6 known loci could be excluded, indicating that the defect gene in this
      microphthalmia family was probably distinct from those of previously reported
      microphthalmia families.

PMID- 15259980
TI  - [Gene delivery system based on low molecular weight polyethylenimine and its
      transfection activity in the skin tissue].
AB  - Low molecular weight polyethylenimine (LMW-PEI) was linked to an expressing
      plasmid contains a green fluorescence protein (GFP) reporter gene and effective
      gene transfer was observed in CM7221 cell line tested. We examined the
      relationship among the molecular weight, structure of PEI and their transfection
      activity and cytotoxicity on CM7221 cell line. We also examined the position and
      continuance time of the GFP reporter gene expressed in the skin tissue of mouse.
      Results showed that LMW-PEI/DNA complexes led to high levels of expression in the
      CM7221 cell line (about 55%). However, with the increasing of PEI molecular
      weight, the transfection activity of PEI was decreasing. There was an increasing
      cytotoxicity with the larger PEI molecules. Further research showed that LMW-PEI
      induced a significant and long-lasting (7 days) expression of the GFP reporter
      gene in the hair vesicle, sweat, gland, sebaceous gland in the mouse skin
      tissues. The LMW-PEI described here is a new, highly efficient and non-cytotoxic
      vector. It would be a useful non-viral vector for gene delivery technology,
      particular useful as simple skin-specific vehicles of therapeutic genes.

PMID- 15259981
TI  - [Relation between root structure and accumulation of anthraquinones of Morinda
      officinalis].
AB  - The histological structures of the roots of Morinda officinalis How of different
      ages were observed, the distribution and accumulation of anthraquinones in the
      root were studied with the help of paraffin section, fluorescent microscope and
      ultraviolet spectrophotometer. The results indicated that the mature structures
      of the roots of M. officinalis were similar to those of common perennial herbs,
      and that the anthraquinones in the root of M. officinalis distributed in
      parenchymatous cells and the content of anthraquinones in the root gradually
      increased in number with age. Based on above mentioned investigation, we came to
      the conclusion that the root of M. officinalis should be collected after four
      years of growing and the top grade root should have well developed phloem and
      thin xylem.

PMID- 15259982
TI  - [The roles of microtubule in internodal cell elongation (Nitellopsis obtusa)].
AB  - The relationship between cell elongation and microtubules (MTs) was investigated
      in characean internodal cells (Nitellops obtusa). First, we examined the
      immunofluorescent localization of MTs in different living stages under confocal
      laser scanning microscope. In young, rapidly elongating cells, MTs were
      predominantly transverse to the long axis of the cell. As the relative growth
      rate fell, transverse MTs gradually decreased, and in non-growing cells,
      longitudinally oriented cortical MTs became most pronounced. Moreover, cells in
      different living stages responded to the treatment of oryzalin (microtubule
      disrupting agent) differently, young active internodal cells seemed to be more
      sensitive. After 40 min incubation of 10 micromol/L oryzalin, nearly all cortical
      MTs in the elongating cells depolymerized. However, in the old, non-growing
      cells, some MT fragments still remained after 3 h treatment of oryzalin. Second,
      we measured the cell growth rates with and without the treatment of oryzalin. In
      young growing cells treated with 10 micromol/L oryzalin, the elongation rates
      were inhibited obviously. When the oryzalin was removed, the elongation rates
      could be recovered to some extent. Interestingly, a time-gap existed between
      microtubule disassembly (40 min) and cessation of cell elongation (100 min). Our
      data confirmed the evidence that MTs are involved in cell elongation.

PMID- 15259983
TI  - [Function of Tra2beta1 proteins in the splicing of neural-specific genes].
AB  - The in vitro studies have shown that Tra2beta1 proteins are important regulators
      in the alternative pre-mRNA splicing in mammalians. To date, the knowledge
      regarding the in vivo function of Tra2beta1 proteins, especially the function in
      regulating the splicing of neural-specific genes and the cell-type specificity of
      the functions is very limited. In the present study, the cell-type specific
      splicing of two neural-specific genes (GluR-B and SMN2), and the function of
      Tra2beta1 proteins in regulation of the splicing were studied in two types of
      cells (COS-1 and PFSK-1) using in vivo splicing models. The results showed that
      the splicing of GluR-B and SMN2 minigenes is cell-type specific, while Tra2beta1
      proteins regulate the splicing of the minigenes in both cell lines in a similar
      pattern. It indicates that the Tra2beta1-regulated splicing of GluR-B and SMN2
      minigenes regulated by Tra2beta1 is not cell-type specific.

PMID- 15259984
TI  - [Cardiomyocyte-like differentiation of human bone marrow mesenchymal stem cells
      after exposure of 5-azacytidine in vitro].
AB  - To investigate the potential of adult mesenchymal stem cells (hMSCs) derived from
      human bone marrow to undergo cardiomyogenic differentiation after exposure of 5
      azacytidine in vitro. A small bone marrow aspirate was taken from the iliac crest
      of human volunteers, and hMSCs were isolated by 1.073 g/mL Percoll and cultured
      in the right cell culturing medium as previously described. The phonotypes of
      hMSCs were identified by flow cytometry. The stem cells were cultured in cell
      culture medium (as control) and medium mixed with 5-azacytidine (5-aza, 3, 5, 10
      micromol/L) (n=5, respectively) for cellular differentiation. We examined
      respectively with immunohischemistry at 21 days of inducement on desmin, cardiac
      specific cardiac troponin I (cTnI), GATA4 & connexin43. The ultrastructures of
      induced cells were examined by transmission electron microscope. The results
      indicated that the hMSCs showed a fibroblast-like morphology with vortex
      distribution in their peak propagation, and express high level of CD44 but
      negative for CD34 and CD45. 20%-30% cells grown after 5, 10 microl/L 5-aza
      treatment connected with adjoining cells and coalesced into myotube structures
      after 14 days. After 21 days of culturing, immunohistochemistry revealed
      expression of desmin, GATA4, cTnI and connexin43 in 5, 10 micromol/L showed
      positive, but no cardiac specific protein were found in neither 3 micromol/L nor
      in control group. The ratio of cTnI positive stained cells in 10 micromol/L group
      were higher than that in 5 micromol/L group (65.3+/-4.7% vs 48.2+/-5.4%, p<0.05).
      Electron microscopy revealed myofilaments were formed. The results indicated that
      purified hMSCs from adult bone marrow can be differentiated into cardiac-like
      muscle cells with 5-aza inducement in vitro and the differentiation is in line
      with the 5-aza concentration.

PMID- 15259985
TI  - [Study on the apoptosis of HL-60 human promyeloid leukaemia cells induced by
      SFPS].
AB  - The inhibition effects of Sargassum fusiforme Polysaccharides (SFPS) on
      proliferation of human HL-60 promyeloid leukemia cells were measured by MTT
      assay. SFPS-induced apoptosis in HL-60 cells was observed by electron microscopy,
      flow cytometry and DNA electrophoresis. The results revealed that SFPS exhibited
      antiproliferative activity which depended on dosage and time. After incubation
      for 24, 36, 48 and 72 h, SFPS had growth inhibitory effect on HL-60 cells with
      IC50 of 390, 362, 402 and 421 mg/L. A ladder-like pattern of DNA fragmentation
      was demonstrated on agarose gel electrophoresis after HL-60 cells induced by SFPS
      at a dose of 300 mg/L and 500 mg/L. Morphological examination by electron
      microscopy showed cells with few microvilli on the surface, chromatin
      condensation and margination, cell shrinkage and the presence of "apoptosis
      bodies". The DNA content analysis of FCM showed pre-G1 cells and increased G2
      period ratio, in addition, it demonstrated that apoptosis induced by SFPS was
      dose-and time-dependent. In conclusion, the antitumor effect of SFPS is relative
      to cell apoptosis and the blocking of G2/M period cells.

PMID- 15259986
TI  - [Expression of human follicle stimulating hormone in insect cells].
AB  - To study the expression of hFSH in insect cells, the cDNA encoding the hFSH beta
      chain was cloned by overlapping-PCR using human chromosome DNA extracted from
      placental tissue as template. Then we constructed expression vector pVL1393/hFSH
      beta using an unfused protein nuclear polyhedrosis virus (AcNPV) expression
      vector. The insect cells (SF9) were cotransfected with the expression vector and
      nuclear polyhedrosis linearized virus DNA, and recombinant viruses AcNPV-hFSH
      beta were collected. The beta subunit of hFSH expressed in plasma of the SF9
      cells was detected by Western blot analysis, and showed apparent molecular masses
      of 21 kDa. After coinfecting SF9 cells with recombinant viruses AcNPV-hFSH beta
      and AcNPV-hCG alpha, secreted heterodimer of hFSH was detected by Western blot
      under non-reducing conditions. The apparent molecular weight of heterodimer was
      about 33 kDa.

PMID- 15259989
TI  - [Establishment of an efficient regeneration system for Chinese cabbage cultured
      in vitro and histological observation of shoot development].
AB  - An efficient plant regeneration system from explants of petiole with cotyledon
      was developed for Chinese cabbage (Brassica campestris ssp. chinensis Makino) in
      our study. High frequency of shoot regeneration was obtained in the medium
      containing BAP 2 mg/L, NAA 0.45 mg/L and 5-7.5 mg/L AgNO3 solution to the half of
      NH4+ concentration's MS basic medium, with 84.3 percent being the highest
      frequency of shoot regeneration in seven Chinese cabbage cultivars and one
      parentage, and the new formed shoots were observed six days after inoculation.
      Factors influencing in vitro explant regeneration were further studied. The
      results showed that there was positive correlation between frequency of shoot
      regeneration and number of shoots per explant. The regeneration plants produced
      flowers and fruits after about 50 days with low temperature treatment from 8
      degrees C to 16 degrees C. Moreover, histological observation indicated that the
      mode of plant regeneration in B. campestris ssp. chinensis was similar to that of
      other Brassica crops, and adventitions buds were formed from globular
      meristematic cluster which derived from the cells of vascular parenchyma at the
      cut surface of petiole.

PMID- 15259987
TI  - [Monocytic differentiation of bone marrow-derived hematopoietic precursors
      controlled by mesenchymal stem cell in absence of exogenous hematopoitic growth
      factors].
AB  - To study the hematopoiesis controlled by mesenchymal stem cell (MSC) in the
      absence of exogenous hematopoietic growth factors in vitro. MSCs were isolated
      and cultured in vitro, and the hematopoietic growth factors secreted by MSCs were
      detected with RT-PCR. Mononuclear cells from bone marrow were seeded in 6-well
      plates in which MSCs had been seeded as feeder cells. After culture for 3 weeks,
      cells in coculture were observed with wright's staining, immunocytochemisty and
      flow cytometry analysis to identify the lineage of hematopoietic cells. The
      results showed that SCF, Flt3 Ligand and M-CSF were detected in MSCs, but G-CSF
      and GM-CSF were not detected. In the coculture system, a number of round shape
      cells grew adherently to the spindle shape MSCs after coculture for 2 weeks.
      Wright's staining displayed that the round shape cells had abundant plasma and
      kidney-shaped or oval nucleus, some cells had typical monocytic morphology, and
      Flow cytometry analysis displayed that the CD45+ round shape cells were positive
      for CD14 and were negative for CD15, CD7, CD19, CD41 and glycoporin A. Our data
      suggested that hematopoietic precursors from bone marrow were able to
      differentiate into monocyte controlled by mesenchymal stem cells in vitro in
      absence of exogenous hematopoitic growth factors, the committed differentiation
      might be regulated by the hematopoietic growth factors secreted by MSCs, and the
      cell-cell contact might also contribute to the differentiation.

PMID- 15259988
TI  - [The role of Cln3 in filamentous growth and invasive growth of Saccharomyces
      cerevisiae].
AB  - Cln3 is one of G1 cyclins in Saccharomyces cerevisiae. In order to study the
      function of Cln3 in cell cycle and morphogenesis, we constructed a cln3 null
      mutant and analyzed its phenotype. Our results indicated that the cln3 null
      mutant was more sensitive to alpha pheromone, and arrested at G1 phase. The
      hypersensitivity to alpha-pheromone was not suppressed by overexpression of SGV1.
      The null mutant showed a different phenotype with that of the other two G1 cyclin
      mutants. The filamentous growth in diploid cells of cln3 mutant was stronger than
      that in wild type cells, while invasive growth of the haploid cells was partially
      inhibited. The results suggested that the Cln3 plays a unique function in
      morphogenesis under a different mechanism with that used by Cln1 and Cln2.

PMID- 15259990
TI  - [Immunocytochemical studies on the phase of differentiation of hatching gland
      cells in brine shrimp, Artemia salina].
AB  - Hatching enzyme (HE), synthesized in hatching gland cells (HGCs), plays vital
      roles in animal hatching. Immunocytochemical techniques employing anti-GST-UVS.2
      antiserum, prepared from Xenopus HE and with specificity to brine shrimp HE, were
      first used to investigate the differentiation and variability of hatching gland
      cells (HGCs) in the hatching process of embryos of brine shrimp, Artemia salina,
      in this study. HGCs with immunoreactivity to anti-GST-UVS.2 antiserum were
      identified, for the first time, in brine shrimp embryos during hatching process.
      Immunocytochemical staining results showed that, (1) HE-positive immunoreactivity
      is really specific to Artemia HE, and its appearance and disappearance are
      closely correlated with the hatching process of Artemia salina. (2) Artemia HGCs,
      first appeared in embryos 5 hours before hatching and disappeared 4 hours after
      hatching, were also a transient type of cells, with an existence period of 9
      hours. (3) The head portion of Artemia embryo is probably the initial position of
      HE secretion, and likely to be the main position of HE secretion as well. The
      detailed process and mechanism need to be studied. (4) The appearance of HGCs is
      in a synchronous mode from places all over the embryos, and their disappearance
      is also in a synchronous mode. (5) The number of HGCs increased gradually along
      with embryo development process and reached a maximum number at hatching.
      Contrarily, the number of HGCs decreased gradually after hatching, and HGCs
      disappeared 5 hours after hatching. However, the intensity of HE-positive
      reaction was almost at the same level at the period of HGCs'presence. (6) Artemia
      HGCs were distributed throughout the body of embryos at all time during their
      presence. Therefore, it can concluded that Artemia HGCs, as a transient type of
      cells, first appeared in embryos 4 hours before hatching and disappeared in
      embryos 5 hours after hatching, and with distinguished patterns of appearance,
      disappearance and distribution in embryos. What is the final destiny of Artemia
      HGCs after hatching? And what is the biological significance of remanet HGCs,
      still existing until 4 hours after hatching, in fresh-hatched Artemia larvae? Is
      it possible that the HGCs are involved in larvae yolk digestion? Moreover, what
      is the molecular mechanism of HGCs' synchronous sudden appearance and
      disappearance? All these questions remain to be further studied and approved.

PMID- 15259991
TI  - At the end of this journey and the beginning of the next.

PMID- 15259992
TI  - Human genetics: can we really eliminate health disparities.

PMID- 15259993
TI  - Predictors of health-promoting behavior of African-American and white caregivers
      of impaired elders.
AB  - Several longitudinal studies have examined declines in health of caregivers, but
      few have explored the health-promoting behavior Because caregivers neglect their
      health, they are at risk for developing a number of physical and psychological
      problems. What is not well known are the factors that contribute to increased
      health-promoting behavior ultimately preventing poor health and premature death.
      Therefore, the purpose of this study was to explore the predictors and the change
      in predictors of health-promoting behavior in African-American and White
      caregivers over a 3-year period. Pender, Murdaugh, and Parsons' (2002) health
      promotion model guided the study. This present study is a secondary data analysis
      of a larger study aimed at examining predictors of health-promoting behavior
      among 66 African-American (n=66) and 110 (n=110) and White caregivers of impaired
      older adults recruited primarily through random digit dialing. The larger data
      set consisted of 391 (N=391) subjects (n=136 African-American; n=255 White). The
      larger prospective study was based on face-to-face interviews. In the original
      study, trained interviewers collected data on depression, psychological distress,
      self-perceived health, religiosity, number of chronic conditions, and demographic
      characteristics using well-established instruments. Data in this present study
      were collected at three time points over a three-year period with one-year
      intervals at Time1 (T1), Time2 (T2), and Time3 (T3). Analysis of the data in this
      present study suggested that, although, the number of health-promoting behaviors
      significantly differed for African-American and White caregivers at T1, T2, and
      T3, no predictors were significantly associated with a change in health-promoting
      behavior over time. Nonetheless, this finding suggests that nurses can develop
      useful information in helping to focus more attention on the health of caregivers
      in the future.

PMID- 15259994
TI  - Socioeconomic status and African Americans' perceptions of cancer.
AB  - A descriptive study was conducted with 139 (N=139) African-Americans (AA) to
      determine the relationship of socioeconomic status (SES) to the perceptions held
      by these individuals regarding cancer screening and early cancer detection,
      cancer risk factors, susceptibility to cancer and thoughts about cancer
      prevention. Findings from this study suggest that among these African-Americans,
      both gender (p = 0.03) and SES (p = 0.01) were significant predictors of
      participants' perceptions regarding cancer risk factors, early cancer detection
      (p = 0.0001), and cancer prevention (p = 0.0001). However there was no
      significant relationship between age, gender SES, and past experience with cancer
      and participants' perceptions of cancer screening and susceptibility to cancer.
      When age and gender were statistically controlled, SES was significantly related
      to participants' perceptions of cancer risk factors, early detection, prevention,
      screening and susceptibility. The findings from this study suggest a need for
      additional research about the relationships between higher SES African-Americans
      and their perceptions of cancer.

PMID- 15259995
TI  - Teenage pregnancy among African-Americans: a qualitative examination of maternal
      education, teenage pregnancy, family dynamics, and conflict resolution.
AB  - This qualitative study is derived from interviews conducted during a larger
      quantitative study that examined facilitators and barrier to communication and
      negotiations in African American families whose teen daughters had one or more
      unwed teen pregnancies. Based on the larger study's findings that the education
      of the teens mother was a statistically significant factor in teen pregnancy, 17
      robust interviews were analyzed in this study and sorted on variables of maternal
      education and teen pregnancies. From the analysis of the data, seven themes
      emerged. Findings indicated that almost all girls reported a lack of contact with
      a father and girls of higher educated mothers tended to have more supportive
      family structures than did girls of lower educated mothers. Most of the families
      rejected the teen pregnancy, although later some accepted the infant. In
      comparison to mothers with a higher level of education, mothers with a lower
      level of education leaned toward more absolutist and negative solutions without
      full discussions about ideas of sex with their teens. Discussion indicated the
      need for interventions based on negotiation principles and tactics.

PMID- 15259996
TI  - Perceptions of overweight and obesity in their community: findings from focus
      groups with urban, African-American caretakers of preschool children.
AB  - Focus groups were conducted with parents, other caretakers, and teachers of
      urban, African-American preschool children attending Head Start. The research
      goal, congruent with the concept of cultural humility, was to elicit target
      population members' perspectives on the nature, importance, prevalence, and
      causes of overweight and obesity in their community, with an emphasis on
      childhood obesity. Themes that emerged revealed that participants defined obesity
      as a more extreme state than the medical definition, these same participants had
      a complex view of the relationships of weight and health, stressed numerous
      environmental factors contributing to obesity. Moreover these participants tended
      to offer suggestions for health professionals and those designing nutrition
      education interventions.

PMID- 15259997
TI  - The love and belonging healthcare needs of HIV infected African-American men upon
      admission to an AIDS dedicated nursing home.
AB  - The purpose of this study was to describe the love and belonging healthcare needs
      of HIV infected African-American men upon admission to an AIDS dedicated nursing
      home. Subjects were 73 (N=73) African-American men 26 to 60 years of age that
      were admitted to an AIDS dedicated nursing home in the Southern New England area
      between 1995 and 1999. Most of the men were single (n = 39) and estranged from
      their immediate families. Many of these men did not have a family member
      supportive of discharge (n = 60) and did not desire discharge back out into the
      community (n = 40). A significant number of these men reported having children (n
      = 40). It has been noted that unmet love and belonging needs lead to a sense of
      loneliness and isolation. Therefore, it is imperative that nurses strive to
      attend to these psychosocial needs in the same manner as they do the physical
      needs of clients entrusted to their care. The African-American men in this study
      found a sense of family in the AIDS dedicated nursing home making it potentially
      a valuable source of needed social support.

PMID- 15259998
TI  - Sociostructural factors influencing health behaviors of urban African-American
      men.
AB  - African-American men are suffering disproportionately from most illnesses.
      Seemingly, action is needed if health disparities that disproportionately affect
      African-American men as compared to their White and female counterparts are to be
      reduced or eliminated. An important step in decreasing common health disparities
      evidenced among African-American men is to understand social factors that act as
      motivators and barriers to seeking care for most of this vulnerable population.
      Following a constructionist epistemology, this study used ethnography to explore
      social structure factors that motivate urban African-American men to seek care.
      Leininger's Culture Care Diversity and Universality Theory guided this study.
      Qualitative interviews were conducted with urban African-American men and other
      individuals in the community to explore understanding, attitudes, and beliefs
      about health. Critical issues examined included social factors associated with
      health seeking behaviors. Themes that emerged from these data indicated that
      critical social factors include: 1) Kinship/significant others; 2) accessibility
      of resources; 3) ethnohealth belief; and 4) accepting caring environment. The
      data also indicated a relationship between these social factors and health
      seeking behaviors of urban African-American men.

PMID- 15259999
TI  - The culture of obesity.
AB  - The purpose of this article is to provide nurses with a model for the culture of
      obesity to more fully understand this distinct cultural group. Although
      individuals from all walks of life are affected by obesity, it occurs at higher
      rates among specific ethnic groups such as African-Americans. Obesity puts
      African-Americans at further risk for health problems such as diabetes,
      hypertension and heart disease. In seeking culturally responsive interventions
      for African-Americans who are obese, it is important to realize that they belong
      to two cultural groups; the African-American culture and the culture of obesity.
      It is hoped that knowledge regarding the culture of obesity, coupled with the
      nurses pre-exiting knowledge about the culture of African-Americans, will provide
      a foundation for the development of culturally responsive nursing interventions
      for African-Americans who are obese. The authors utilized Giger and Davidhizar's
      Transcultural Assessment Model (1999), as the guiding framework to present a
      model of the culture of obesity.

PMID- 15260000
TI  - Eliminating structural and racial barriers: a plausible solution to eliminating
      health disparities.
AB  - It is essential to critically and systematically analyze the literature to
      determine what impact the historical effects of individual and institutional
      racism have had on the prevailing health disparities across racial/ethnic groups
      including African-Americans, Hispanic Americans, Asian Americans, and American
      Indians. Moreover given the historical significance of institutional racism, a
      review of health disparities across ethnic minority groups could ultimately
      ayugment understanding in order to ensure culturally competent health care to
      these vulnerable populations.

PMID- 15260001
TI  - [Legal aspects of medical continuing education].

PMID- 15260002
TI  - The use of tumor necrosis factor neutralization strategies in rheumatologic
      disorders other than rheumatoid arthritis in Lebanon.

PMID- 15260003
TI  - Putting the Public into the public health curriculum: a case study.

PMID- 15260004
TI  - The differential diagnosis.

PMID- 15260005
TI  - Cover note: University of Illinois at Chicago College of Medicine.

PMID- 15260006
TI  - Building a new nursing service: respectability and efficiency in Victorian
      England.

PMID- 15260007
TI  - [Standards, options and recommendations for the use of recombinant erythropoietin
      (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in
      oncology for patient undergoing radiotherapy-update 2003].
AB  - CONTEXT: "The Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of French Cancer Centres
      (FNCLCC), the twenty French cancer centres, and specialists from French public
      universities, general hospitals and private clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and the outcome of cancer patients. The methodology is based on a literature
      review and critical appraisal by a multidisciplinary group of experts, with
      feedback from specialists in cancer care delivery. OBJECTIVES: To update the
      Standards, Options and Recommendations clinical practice guidelines for the use
      of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO)
      in the management of anaemia in oncology for patient undergoing radiotherapy.
      METHODS: The working group identified the questions requiring up-dating from the
      previous guideline. Medline and Embase were searched using specific search
      strategies from January 1999 to October 2002. Literature monitoring was performed
      to identify randomised clinical trials published between October 2002 to November
      2003. In addition several Internet sites were searched in October 2002. RESULTS:
      There is no standard attitude for use of rHuEPO in patients undergoing
      radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT
      cancer receiving radiotherapy alone. In patients undergoing curative
      radiotherapy, it is recommended to correct anaemia under I Og/dL using
      transfusion rather than rHuEPO. When the haemoglobin concentration is between
      12g/dL and 14g/dL initial use of rHuEPO can be an option under certain conditions
      for radiochemotherapy if the risk of anaemia is high with the chemotherapy
      regimen used. Anaemic patients should be included in clinical trials to clarify
      the impact of rHuEPO in terms of local control of the tumour and survival.

PMID- 15260008
TI  - Secondary hyperparathyroidism after removal of a parathyroid adenoma.
AB  - OBJECTIVE: To report a case of secondary hyperparathyroidism after successful
      extirpation of a single parathyroid adenoma. METHODS: We present the clinical,
      pathologic, and laboratory findings in a 29-year-old woman with primary
      hyperparathyroidism. Serum calcium, phosphorus, and parathyroid hormone (PTH)
      concentrations, bone turnover, and results of densitometry studies before and
      after parathyroidectomy were evaluated. RESULTS: A young woman had noted fatigue,
      nervousness, weight loss, back pain, and polyuria for 3 months. She had
      hypercalcemia, hypophosphatemia, high PTH concentrations, and increased markers
      of bone turnover. Subperiosteal bone resorption of the distal phalanges, femoral
      and spine osteopenia, and osteoporosis in the radius were found. A nodule was
      palpated in the right side of the neck and localized by ultrasonography, nuclear
      medicine imaging studies, and computed tomography. A single parathyroid adenoma
      was removed; no other parathyroid lesions were found. Postoperatively,
      hypoparathyroidism developed. Supplementation with intravenously and orally
      administered calcium and vitamin D relieved her symptoms and normalized the serum
      calcium and phosphate concentrations. Subsequently, however, PTH levels were high
      and remained above the upper normal range for 27 weeks of follow-up, while
      calcium concentrations remained normal. These findings were consistent with
      physiologic secondary hyperparathyroidism due to "hungry bone syndrome," in the
      setting of normal renal function. Postoperatively, markers of bone resorption
      declined faster than those of bone formation, and sequential densitometry studies
      showed increments in bone mineral density. CONCLUSION: This patient with primary
      hyperparathyroidism fulfilled the criteria for surgical extirpation of the neck
      mass. The prolonged postoperative increase in PTH level was indicative of
      physiologic secondary hyperparathyroidism that resolved gradually, along with the
      normalization of the increased bone turnover and bone mineral density during the
      40-week observation period.

PMID- 15260009
TI  - The case of the elusive androgen.
AB  - OBJECTIVE: To describe a case of androgen excess and discuss the important
      factors in diagnosis and management. METHODS: A case report is presented of a
      postmenopausal woman who had had severe hirsutism for 18 months. Her history,
      clinical and laboratory findings, treatment, and outcome are chronicled. The
      pertinent literature--especially that related to the differential diagnosis of
      hyperandrogenism--is also reviewed. RESULTS: A 62-year-old woman had progressive
      hirsutism of the face, back, and abdomen as well as alopecia of the scalp, for
      which spironolactone therapy had proved ineffective. Laboratory studies showed a
      testosterone level of 644 ng/dL. Preoperative evaluation pointed to an ovarian
      source of testosterone. After total abdominal hysterectomy and bilateral
      oophorectomy, histologic examination of the ovaries showed bilateral hilar cell
      hyperplasia. Three months later, the serum testosterone level remained high (556
      ng/dL), and repeated computed tomography of the abdomen disclosed a previously
      unseen 9-mm adenoma of the left adrenal gland, which was removed
      laparoscopically. Because of a persistently high testosterone value (546 ng/dL),
      the patient underwent dexamethasone suppression studies, followed by adrenal
      stimulation with corticotropin; no pathologic findings were demonstrated.
      Finally, gonadotropin suppression with nafarelin, 200 mg intranasally daily for 6
      weeks, yielded a prompt and sustainable decrease in the testosterone level. This
      result was associated with dramatic clinical improvement. CONCLUSION: It is
      speculated that the patient had residual testosterone-producing tissue
      originating from primitive mesenchymal cells from the urogenital ridge, which was
      responsive to gonadotropins, in an unidentified abdominal or pelvic site.

PMID- 15260010
TI  - American Association of Clinical Endocrinologists Medical Guidelines for clinical
      practice for the evaluation and treatment of hypogonadism in adult male patients-
      2002 update.
AB  - In these clinical practice guidelines, specific recommendations are made for
      determining the most effective methods of diagnosing and treating hypogonadism in
      adult male patients. The target populations for these guidelines include the
      following: (1) men with primary testicular failure requiring testosterone
      replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin
      deficiency or dysfunction who may have received testosterone replacement therapy
      or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men
      with symptoms relating to testosterone deficiency who could benefit from
      testosterone replacement therapy. Initial hormonal evaluation generally consists
      of a testosterone determination, in conjunction with a free testosterone or sex
      hormone-binding globulin level, inpatients with clear symptoms and signs but
      normal-range total testosterone, follicle-stimulating hormone, luteinizing
      hormone, and prolactin levels. Other possible tests include semen analysis,
      pituitary imaging studies, genetic studies, bone densitometry, testicular
      ultrasonography,testicular biopsy, and specialized hormonal dynamic testing.
      Therapeutic options generally consist of testosterone replacement by injections,
      patches, or topically applied gel in hypergonadotropic patients and in
      hypogonadotropic patients not interested in fertility. In hypogonadotropic
      patients interested in fertility, gonadal stimulation option scan be considered,
      including human chorionic gonadotropin stimulation therapy with or without human
      menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin
      releasing hormone pump therapy. These therapies may be combined with assisted
      reproductive technologies such as in vitro fertilization with intracytoplasmic
      sperm injection, which may allow pregnancy to occur with very low numbers of
      sperm.

PMID- 15260012
TI  - Sour grapes.

PMID- 15260011
TI  - American Association of Clinical Endocrinologists medical guidelines for clinical
      practice for the evaluation and treatment of hyperthyroidism and hypothyroidism.
AB  - These clinical practice guidelines summarize the recommendations of the American
      Association of Clinical Endocrinologists for the diagnostic evaluation of
      hyperthyroidism and hypothyroidism and for treatment strategies in patients with
      these disorders. The sensitive thyroid-stimulating hormone (TSH or thyrotropin)
      assay has become the single best screening test for hyperthyroidism and
      hypothyroidism, and in most outpatient clinical situations, the serum TSH is the
      most sensitive test for detecting mild thyroid hormone excess or deficiency.
      Therapeutic options for patients with Graves' disease include thyroidectomy
      (rarely used now in the United States), antithyroid drugs (frequently associated
      with relapses), and radioactive iodine (currently the treatment of choice). In
      clinical hypothyroidism, the standard treatment is levothyroxine replacement,
      which must be tailored to the individual patient. Awareness of subclinical
      thyroid disease, which often remains undiagnosed, is emphasized, as is a system
      of care that incorporates regular follow-up surveillance by one physician as well
      as education and involvement of the patient.

PMID- 15260013
TI  - Visual vignette. Cutis verticis gyrata (GVG) in acromegaly.

PMID- 15260016
TI  - Heterotopic bone formation following hip arthroplasty in Paget's disease.
AB  - Heterotopic bone formation in soft tissues occurs commonly in Paget's disease
      patients following a primary total hip arthroplasty (THA). The nature of this
      heterotopic bone has not been documented. In this report, we show that the
      heterotopic bone removed 14 years after primary THA in a case of Paget's disease
      was sclerotic, contained prominent mosaic cement lines and showed increased
      remodelling activity on the bone surface. In addition to these typically Pagetic
      histological features, it was noted ultrastructurally that the osteoclasts
      contained characteristic intranuclear viral-like inclusions. In contrast, the
      foreign body macrophages found in the joint pseudocapsule and pseudomembrane,
      which are a population of mononuclear precursor cells from which osteoclasts can
      be formed, did not contain viral-like inclusions. These findings are of interest
      regarding the pathogenesis of heterotopic bone formation following hip
      arthroplasty and the ontogeny of Pagetic osteoclasts.

PMID- 15260017
TI  - Numerical injury assessment scales and scoring systems.

PMID- 15260019
TI  - ["Facial pain" in german textbooks in pain medicine].

PMID- 15260018
TI  - [Current state of wavefront guided corneal surgery to correct refraction
      disorders].
AB  - The present review describes the current status of wavefront-guided corneal
      surgery and up-to-date results. Wavefront-guided LASIK procedures performed to
      date achieved uncorrected vision of i.o or better in a larger number of patients
      than with conventional LASIK surgery, but the "eagle eye" has remained the
      exception. In part of the patients reductions of higher order aberrations could
      be obtained, but in the majority of ca-ses an increase was observed. This
      increase was however less than with conventional LASIK surgery. Correction of
      higher order aberrations has not yet been perfected since the predictability of
      corrections appears to be deserving of improvement on the one hand and
      aberrations are still induced by the technique on the other hand.

PMID- 15260020
TI  - Transfer regulations and cost-effectiveness analysis.
AB  - Recent scholarship on regulatory oversight has focused on cost-benefit analysis
      of prescriptive regulations--regulations that restrict behavior such as pollution
      -and their use to cure market failures, and has overlooked the vast number of
      transfer regulations. Transfer regulations are regulations that channel funds to
      beneficiaries. These regulations are authorized by statutes that establish
      entitlement programs like Medicare and Social Security, pay one-time
      distributions to victims of misfortunes such as natural disasters and the 9/11
      terrorist attack, and fund pork barrel spending. Cost-benefit analysis cannot be
      used to evaluate transfer regulations because all transfer regulations fail cost
      benefit analysis; cost-effectiveness analysis, however, can be used to evaluate
      transfer regulations. Although executive orders appear to require agencies to use
      cost-effectiveness analysis to evaluate transfer regulations that have a large
      economic impact, the agencies' record is dismal. Most agencies fail to perform
      cost-effectiveness analysis, and other agencies perform cost-effectiveness
      analysis incorrectly. More vigorous Office of Management and Budget and,
      possibly, judicial review could improve the quality of distributive regulations.

PMID- 15260021
TI  - The problems of pouring-rights contracts.

PMID- 15260022
TI  - Risk and the welfare state.
AB  - The British welfare state developed as a state-centred response to the problem of
      handling the risks encountered in a typical life-course. The influential work of
      Giddens and others implies that the traditional welfare state is under attack
      from two directions: a changing international politico-economic environment
      limits the freedom of national governments to pursue independent policies
      involving relatively high taxation to finance social spending. At the same time,
      changes in the experience of risk and declining confidence in the expertise of
      welfare state planners and professionals undermine support for state-centred
      solutions. This approach fails to acknowledge that available non-state services
      are often inadequate to meet many everyday life risks and that the authority of
      private sector advisers, insurers and professionals is also increasingly open to
      question. This article discusses whether people reject welfare state solutions to
      problems of risk in the context of research on the perceptions and behaviour of
      people buying or selling their homes, considering provision for long-term care
      needs and defrauding social security carried out by the ESRC's Economic Beliefs
      and Behaviour programme. Individual responses endorse the continued provision of
      state welfare in order to meet unprovided risks alongside disenchantment with the
      record of both state and private professionals and planners and awareness that
      state retrenchment requires greater individual responsibility for meeting one's
      own needs. The theory of risk society requires development to recognize that
      citizens are not necessarily alienated from state welfare.

PMID- 15260023
TI  - Socio-economic re-structuring and employment: the case of minority ethnic groups.
AB  - The consequences of major changes in employment, due to the decline of
      manufacturing and the growth of the service sector, have not been well
      documented, nor theorized, in the sociology of ethnic relations, even in recent
      studies. For example, Blumer's classic argument that economic development adapts
      to 'race relations', rather than the reverse as predicted by the modernization
      school, has not been either empirically resolved or conceptually applied to the
      UK. By adapting data from the Labour Force Survey and the Census, the paper
      begins to fill this gap with a detailed account of three main minority ethnic
      groups, and a separate analysis of male and female employment. It is demonstrated
      that, contrary to assumptions that members of the minority ethnic groups suffered
      most from de-industrialization, they actually did rather well, and in some cases
      did better than the majority population. These findings are re-conceptualized as
      collective social mobility, as part of a review of a number of conceptual
      frameworks in the light of the data.

PMID- 15260024
TI  - Routes of success: influences on the occupational attainment of young British
      males.
AB  - Using data from the National Child Development Study, the paper develops a
      complex path model predicting the occupational grade achieved by 4,298 employed
      British males at age 33. Most British social mobility research has been based in
      the 'class structurationist' tradition, and the paper begins by comparing this
      with the 'status attainment' tradition, which is more common in the USA. The
      class structurationist approach has rarely analysed the factors influencing
      individual occupational attainment, and those working in this tradition in
      Britain have often assumed that people from working-class origins fare worse on
      average than those from the middle class because of factors associated with their
      class disadvantage rather than any difference in individual characteristics such
      as ability or ambition. Status attainment research, however, has generally found
      that individual ability and motivation are the key factors influencing
      occupational attainment, and that class origins count for comparatively little.
      Using various measures of class origins, parental support, qualifications, and
      individual ability and ambition, the paper goes on to develop a linear structural
      equations model which achieves a good fit to the data. The model demonstrates
      that individual ability is by far the strongest influence on occupational
      achievement, that motivation is also important, and that factors like class
      background and parental support, while significant, are relatively much weaker.
      The paper concludes that occupational selection in Britain appears to take place
      largely on meritocratic principles.

PMID- 15260025
TI  - Governing police practice: limits of the new accountability.
AB  - The advent of public-sector managerialism has brought with it a new principle of
      police accountability in Western democracies such as Australia and Britain. The
      new accountability gives emphasis to managerial rather than legal or public
      interest standards, favours external oversight combined with self-regulation
      rather than centralized control, and promotes risk management rather than rule
      enforcement. This article makes use of the experience of an Australian police
      force to show that the new accountability has not been successful in holding
      police accountable, while elements of the old accountability have re-emerged to
      dominate public debates. It is argued that in the area of police governance, the
      neo-liberal state does not necessarily pursue a coherent strategy of 'acting at a
      distance' (cf. Miller and Rose 1990), partly because of the inability of
      accountability technologies to deliver substantially the promised policy outcomes
      and partly because of the sensitivity of its political arm to the public's moral
      outrage against corruption (cf. Garland 1996).

PMID- 15260026
TI  - Norbert Elias and the civilized prison.
AB  - This paper employs an Eliasian perspective to provide an historical overview to
      the contemporary crisis in British prisons. It argues that some of the roots of
      this crisis lie within the very attempts to bring prison development in line with
      the cultural values of modern society.

PMID- 15260027
TI  - The barbarism of civilization: cultural genocide and the 'stolen generations'.
AB  - Norbert Elias suggested that 'civilization' involves the transformation of human
      habitus so that violence of all sorts is gradually subjected to greater and more
      sophisticated forms of management and control, whereas 'decivilization'
      encompasses processes which produce an increase in violence and a breakdown in
      the stability and consistency of on-going social relations. What remains
      unexplored is the extent to which 'civilizing offensives', the self-conscious
      attempts to bring about 'civilization', have revolved around essentially violent
      policies and practices. This paper examines the systematic removal of indigenous
      Australian children from their families, largely for the social engineering
      purpose of the gradual and systematic annihilation of Aboriginal cultural
      identity. At the time, these policies and practices were constructed by most
      observers as contributing to the 'welfare' of Australian Aborigines, and this
      intersection of welfare and violence raises the possibility that civilization and
      decivilization, rather than being different processes which may or may not run
      alongside each other, interpenetrate each other so that, under certain
      circumstances, societies are 'barbaric' precisely in their movement towards
      increasing civilization. It may also be possible to describe the move away from
      the systematic removal of Aboriginal children since the 1970s as itself part of a
      civilizing process, an increasing recognition of the human rights of Australian
      Aborigines and of the inhumanity of those policies and practices. The paper
      concludes by addressing the implications for theories of civilization and
      decivilization, as well as more generally for our contemporary understanding of
      what it means to be a 'civilized' modern citizen.

PMID- 15260028
TI  - The concept of adequate causation and Max Weber's comparative sociology of
      religion.
AB  - Max Weber's The Protestant Ethic and the Spirit of Capitalism, studied in
      isolation, shows mainly an elective affinity or an adequacy on the level of
      meaning between the Protestant ethic and the 'spirit' of capitalism. Here it is
      suggested that Weber's subsequent essays on 'The Economic Ethics of World
      Religions' are the result of his opinion that adequacy on the level of meaning
      needs and can be verified by causal adequacy. After some introductory remarks,
      particularly on elective affinity, the paper tries to develop the concept of
      adequate causation and the related concept of objective possibility on the basis
      of the work of v. Kries on whom Weber heavily relied. In the second part, this
      concept is used to show how the study of the economic ethics of India, China,
      Rome and orthodox Russia can support the thesis that the 'spirit' of capitalism,
      although it may not have been caused by the Protestant ethic, was perhaps
      adequately caused by it.

PMID- 15260029
TI  - Two arguments for 'covert methods' in social research.
AB  - In some 'covert' participant-observation studies, social researchers defend their
      omission of informed consent on the basis of a need to protect subjects from
      apprehension, nervousness, or even criminal prosecution. In other instances,
      researchers contend that deception is rampant in society, and that their methods
      are no more immoral than the behaviour that ordinarily prevails. These defenses
      of covert methods fail to appreciate the range of risks that may be involved, and
      in the latter case, fail to show that these methods are in fact morally
      indistinguishable from the 'deception' that people typically engage in.
      Ultimately, these proposed defenses of covert methods succeed only in arousing
      greater concern about informed consent in social research, and the researcher's
      privilege in bypassing it.

PMID- 15260030
TI  - [On the importance of respiratory viruses].

PMID- 15260031
TI  - [The prognosis of lung cancer: any progress since TNM?].

PMID- 15260032
TI  - [Should we tell the patient the truth?].

PMID- 15260033
TI  - [Evidence based medicine in general, evidence based pulmonology in particular].

PMID- 15260034
TI  - [A quick reader's guide through the labyrinth of the reparation of professional
      diseases].

PMID- 15260035
TI  - [Influenza vaccine: a duty for caregivers].

PMID- 15260036
TI  - [Epidemiology and diagnosis of respiratory syncitial virus in adults].
AB  - INTRODUCTION: Respiratory syncytial virus (RSV) is rarely searched for in
      respiratory infections in adults. This study assessed its frequency and
      diagnosis. METHODS: Three separate studies were conducted in adults presenting
      with (1) a flu-like illness, (2) a lower respiratory tract infection in the
      community, and (3) a severe pneumonia requiring hospitalisation. The diagnosis of
      RSV infection was sought by PCR in all cases, and compared to antigen detection
      and culture in two studies. RESULTS: RSV was identified in 20 (11.7%) of 170
      influenza-vaccinated adults suffering from flu-like symptoms. In the 270 cases of
      non-severe lower respiratory tract illnesses in the community, viruses were
      identified in 86 (31.8%) cases, with RSV accounting for 13 (4.8%). In the 164
      cases of acute bronchitis, a virus was detected in 64 (36.7%) of which 11 (6.3%)
      were RSV, 37 (21.3%) rhinovirus, 5 influenza viruses A and B, and 12 other
      viruses. In the 60 cases of infective exacerbations of chronic bronchitis,
      rhinovirus was detected in 9 (15%) and para-influenza 3 virus in 2 cases. In the
      21 acute pneumonia's, 1 RSV, 1 influenza virus A and 2 rhinovirus cases were
      detected as well as 1 RSV, 1 parainfluenza 3 viruses and 4 rhinovirus cases in
      the 11 lower respiratory tract illnesses in patients with pre-existing lung
      disease. There were overall 19 viral and bacterial associated infections.
      Finally, in the 51 acute pneumonias hospitalised with respiratory distress
      syndrome, a virus was identified in 17 (33.3%) cases, including 3 (5.5%) RSV, 6
      influenza A, 3 rhinovirus, 2 adenovirus, 2 herpes simplex virus and 1
      cytomegalovirus. There were 6 bacterial-associated infections, and 4 were
      hospital-acquired. All RSV-infected patients were old people and had chronic
      pulmonary or cardiac disease. CONCLUSIONS: In adults, RSV is a frequent cause of
      flu-like symptoms. It can sometimes cause lower respiratory tract illness, which
      can be severe, and should be considered in the differential diagnosis in such
      cases. The PCR method is a particularly effective diagnostic test, but as yet is
      not routinely available.

PMID- 15260037
TI  - [Asthma education - the patient's response. The results of an automated analysis
      of an interview].
AB  - INTRODUCTION: Asthma education is a subject of topical interest and is included
      in the current guidelines. Everyone agrees on the importance of the concepts of
      the disease in determining the patient's therapeutic behaviour but there have
      been few studies of the patient's views on asthma education. METHODS: 42
      asthmatics replied to an interview bearing on the following themes: asthma in
      daily life, therapeutic education and methods of education. The interviews were
      analysed by the ALCESTE software programme (analysis of co-occurrent lexemes in
      the simple wording of a text) that extracts the major significant components of a
      text. RESULTS: The first theme was dominated by thoughts about treatment, long
      term rather than acute, and by problems of everyday life and relationships with
      others; the second by the organisation, presentation and form of education and
      the third by thoughts about the information required, its relevance and
      implications. CONCLUSIONS: Asthmatic patients' concepts of therapeutic education
      are poorly defined. There expectations are implicit but they are not fully aware
      of them. Clarifying these factors will be a way of creating a better basis for an
      educational programme.

PMID- 15260039
TI  - [The effects of smoking and the degree of nicotine dependence on aerobic capacity
      in sportsmen].
AB  - AIM: To assess the effects of smoking and the degree of nicotine dependence on
      aerobic capacity in smokers undergoing endurance training. METHODS: 126 smokers
      aged between 18 and 31 years playing in the football teams of the Congolese first
      (n = 64) and second divisions (n = 64) co-operated voluntarily in the study.
      Aerobic capacity was determined by Cooper's running test. Absolute VO2max and
      that related to body weight were subsequently calculated. The degree of nicotine
      dependence of each subject was assessed by the Fagerstrom questionnaire. A
      control group consisted of 125 non-smokers playing at the same level. RESULTS:
      The values of VO2max achieved by the smokers were significantly less (p < 0.05)
      than those achieved by the non-smokers. The first division players had a higher
      aerobic capacity than the second division players. Moreover the analysis of
      variance showed an influence of nicotine dependence on aerobic capacity. The
      subjects who were heavily dependent on nicotine had lower VO2max values than
      those less dependent. Moreover for the same level of dependence there were
      differences between the first and second division players. CONCLUSION: The
      inhalation of tobacco smoke leads to an alteration in aerobic capacity. This is
      directly influenced bythe degree of nicotine dependence whatever the level of
      training of the subject.

PMID- 15260038
TI  - [Malignant pleural mesothelioma: radiotherapy for the prevention of seeding
      nodules].
AB  - INTRODUCTION: Radiotherapy for the prevention of skin nodules appearing at the
      sites of aspiration, needle biopsies, chest drains or surgical incisions is the
      only treatment currently recommended for malignant mesothelioma. METHODS: 59
      patients suffering from this condition were identified from the database of the
      Nantes Regional Cancer Centre. 33 received prophylactic irradiation, 25 did not
      and 1 was excluded. RESULTS: The treated group showed typical demographic and
      histological features. The delay in initiating radiotherapy ranged from 10 to 123
      days and several different treatment regimes were used. In the treated group 7
      out of 32 patients developed nodules following radiotherapy with 4 recurrences in
      the treated and 3 in the untreated areas. The mean interval before recurrence was
      9 months (range 3 to 17 months). The recurrence rate was lower in the treated
      (21%) than in the untreated group (48%;12 out of 25). CONCLUSIONS: The poor
      results compared with the reference series may be explained by a longer follow-up
      (mean 12 months), less thorough treatment of all puncture sites and a very long
      delay before treatment (mean 37 days).

PMID- 15260040
TI  - [What perception have smokers of nicotine and tar yields of cigarettes?].
AB  - INTRODUCTION: Advertising information on cigarette package participate to the
      reduction of health risks from smoking. Impact on smokers has been poorly
      studied. This study intended to determine the smoker perception of nicotine and
      tar yields of cigarettes. METHODS: Consulting in an outpatient smoking cessation
      clinic, 171 smokers answered freely and spontaneously to a questionnaire
      evaluating their perception of nicotine and tar yields, cigarette consumption
      (number and brand), nicotine dependence. Simultaneously, biological tobacco
      markers were measured. RESULTS: The number of cigarettes, nicotine dependence and
      specific tobacco markers were not significantly different according to the
      cigarette type: "full savour", "light" or "ultra light". Women smoked less than
      men and 54% preferred "light" cigarettes versus 37% of men. These smokers were
      entering a tobacco cessation program, it was assumed they had lead a prior
      reflection about their smoking habits. Only 8% of them gave the correct values of
      nicotine and tar yields and 14% gave approximate values. Tar levels were highly
      underestimated. CONCLUSIONS: This study shows that smokers have actually no
      interest for nicotine and tar yields. As the new decree which modifies
      manufacture's obligation concerning the legal mentions, is applicable in January
      2004 in France; our conclusion may change in the future.

PMID- 15260041
TI  - [Breaking bad news by the respiratory physician: a therapeutic process].
AB  - INTRODUCTION: The profession of respiratory medicine is often involved in
      communicating bad news, dealing with handicapping chronic disease or a poor
      prognosis. STATE OF THE ART: Particularly when dealing with a cancer diagnosis,
      the "bad news" process is poorly described in the literature. The communication
      techniques that are used are specific to this highly charged encountered and they
      are neither innate nor widely taught. Yet the performance of the doctor at this
      crucial stage has a bearing on the patient throughout their clinical course and
      later complications. Ethical values, in particular respect of the patient's right
      to autonomy, as well as psychological and practical issues, govern the decision
      of giving the diagnosis to the patient or their next of kin. PERSPECTIVES: From
      the patient's point of view, the breaking of bad news will be language, delivered
      with therapeutic intentions, which describes a significant loss. This language
      has the potential to unleash a mourning process, a calling into question and
      readjustment of direction and future plans. This process and its stages, if
      recognised by the doctor, can be harnessed so thatthe patient can by assisted
      into making correct therapeutic decisions whilst reinforcing their sense of
      autonomy. A study, which looks closely at the mechanisms of this process, and the
      benefits delivered, as well as the necessary training required by doctors,
      remains to be done. CONCLUSION: Breaking bad news to a patient is therefore as
      much a therapeutic process as the sharing of information.

PMID- 15260042
TI  - [Prognostic indicators in stage I non-small cell lung cancer].
AB  - INTRODUCTION: Determinating the prognosis of patients with stage I non-small cell
      lung cancer (NSCLC) is a challenge. Since up to 30% of patients who have
      undergone surgical resection experience recurrence, generally in distant organs,
      it is reasonable to postulate that neo-adjuvant or adjuvant treatments might be
      useful. Better knowledge of prognostic factors could perhaps define which patient
      populations should be targeted with such treatments. STATE OF THE ART: Numerous
      potential prognostic factors, relating to the disease (TNM classification,
      histology, tumor size, blood vessels invasion, micro-metastasis, serum or
      molecular markers), the patient (gender, age, co-morbidity) as well as the
      treatment (delay, resection, lymph node dissection, neo-adjuvant and adjuvant
      treatments), are discussed. PERSPECTIVES: These prognostic factors should be
      integrated into the design of future clinical trials of chemotherapy and/or
      radiotherapy attempting to evaluate the effectiveness of various combinations of
      neo-adjuvant or adjuvant therapies. CONCLUSIONS: These factors may offer the
      opportunity to clinically and biologically characterize the different subgroups
      of patients, leading to a more rational, and perhaps individualized, choice of
      therapy.

PMID- 15260043
TI  - [Micro-metastases and non-small cell lung cancer].
AB  - INTRODUCTION: Non-small cell lung cancer has a poor prognosis, including those
      with operable, apparently localised, disease. Preoperative staging investigations
      and histo-pathological analysis are poor at detecting small clusters of tumour
      cells, particularly in lymph nodes. STATE OF THE ART: New methods based on
      immunohistochemistry, or molecular biology, have been developed to detect these
      so-called micro-metastases. We present a ten-year review of the literature
      published on this topic. PERSPECTIVE: These publications primarily reported on
      the detection of micro-metastases within mediastinal lymph nodes removed at
      operation in order to identify patients at risk of recurrence, for whom adjuvant
      therapy might be offered. CONCLUSIONS: Lymph node micro-metastases have been
      demonstrated to be an independent prognostic factor for survival, especially in
      stage I patients. On the other hand, the presence of bone marrow micro-metastases
      did not appear to be of significant prognostic value in non-small-cell lung
      cancer. Finally, the clinical relevance of circulating tumour cells is still
      debatable, although recent published studies show interesting results.

PMID- 15260045
TI  - [Concordance between two variables: numerical approaches (qualitative
      observations - the kappa coefficient-; quantitative measures].

PMID- 15260044
TI  - [The "COPD emergency 2003" study: a description of the hospital management of
      exacerbations of COPD].
AB  - CURRENT SITUATION: Despite its impact on public health and numerous
      recommendations COPD remains under-diagnosed and its care pathways are not well
      known. Exacerbations are common presentations of the illness and contribute
      greatly to its impact on the health of the individual and the community. Despite
      this the methods of their management in hospital have not been precisely
      described. The purpose of the prospective study "COPD emergency 2003" is to
      describe these different aspects of the management of COPD and to study their
      determining factors. MATERIALS AND METHODS: It is a prospective, multicentre
      observational study of all the exacerbations of COPD managed as emergencies in
      public and private hospitals during a two-month period. Enrolment takes place
      between October 2003 and January 2004. The analysis will begin when the last
      patient has been discharged from hospital. EXPECTED RESULTS: The data obtained
      will allow identification of those aspects of the management of COPD and its
      exacerbations that are heterogeneous or in conflict with the current guidelines
      as well as the patient care pathways. In the future this study should help target
      the approaches aimed at improving the outcomes of patients suffering from COPD.

PMID- 15260046
TI  - [Concordance between two variables: graphical approach (Bland and Altman's
      method)].

PMID- 15260047
TI  - [Late presentation of a traumatic pulmonary arteriovenous malformation].
AB  - INTRODUCTION: Pulmonary arteriovenous malformations (PAVM) are rare, and most
      often of congenital origin. Among secondary causes of PAVM, trauma is
      exceptional. CASE REPORT: We describe here one such case, discovered very late
      over twenty years after a thoracic perforing wound. Recent vascular imaging
      techniques (angio-CT scanning and -RMI) have largely contributed to their
      diagnosis, but direct pulmonary arteriography remains the reference technique
      preoperatively when surgery is required. In all cases, treatment is as
      conservative as possible, and embolization of small sized PAVM, even multiple, by
      coils has become the standard procedure. However, surgery is required when the
      PAVM is large and/or proximal, particularly when its feeding vessel is complex.
      Itwas the case of our patient, who has been cured by a lobectomy. CONCLUSIONS:
      PAVM are rare but should be sytematically searche for in case of hypoxemia along
      with a pulmonary nodule.

PMID- 15260048
TI  - [Bronchial erosion of mediastinal lymphadenopathy associates with Hodgkin's
      disease].
AB  - INTRODUCTION: Erosion of mediastinal adenopathy into the bronchial tree is
      classically associated with tuberculosis. We describe two cases of of such
      bronchial erosion with Hodgkin's disease. CASE REPORT: The first case was of a
      seventy-year old man with a history of pulmonary silicosis. A sub-carenal mass
      was identified during investigation of chronic cough. The bronchoscopy revealed
      an inflammatory stenosis due to Hodgkin's disease. The second case was of a
      thirteen-year old child whose Hodgkin's disease was thought to be in remission
      following treatment. The erosion of mediastinal adenopathy into the main left
      bronchus produced complete left pulmonary atalectasis, which required
      endobronchial stenting. CONCLUSIONS: In both cases, rigid bronchoscopy provided a
      histological diagnosis with diagnosis of Hodgkin's disease in the first case, and
      identification of recurrence in the other one. These cases are unusual. Such
      complications are usually complications of radiotherapy. Classically, erosion of
      mediastinal adenopathy into the bronchial tree is tuberculous in origin but they
      can be neoplasic.

PMID- 15260049
TI  - [Endocrine and pulmonary histiocytosis: a case diagnosed through stereotoxic
      biopsy].
AB  - INTRODUCTION: Despite intensive investigation, the pulmonary lesions of
      Langerhans cell histiocytosis can sometimes prove difficult to yield a diagnosis
      of this potentially multi-focal disease. CASE REPORT: We report the case of a
      sixteen year old woman, who presented with a hypothalamo-hypophyseal mass
      associated with endocrine clinical signs, dyspnoea, and micro-nodular pulmonary
      lesions on computerised tomography. A Langerhans cell histiocytosis was initially
      suspected, but then thought unlikely in the light of negative pulmonary
      investigations and spontaneous regression of the pulmonary lesions. However, an
      increase in the size of the cerebral mass prompted a brain biopsy finally
      confirming the diagnosis of Langerhans cell histiocytosis. CONCLUSIONS: This case
      report identifies a possible dissociation between the clinical courses of
      cerebral and pulmonary Langerhans cell histiocytosis, and confirms the usefulness
      of extra-thoracic biopsies in making a diagnosis on the disseminated form of the
      disease.

PMID- 15260050
TI  - [Pulmonary nocardiosis and broncho-oesophageal fistula in a patient infected with
      HIV].
AB  - INTRODUCTION: We report a case of extensive pulmonary nocardiosis in a patient
      infected with HIV. CASE REPORT: It presented as bilateral cavitated masses and
      bulky necrotic mediastinal lymphadenopathy causing broncho-oesophageal fistulae.
      There was associated infection with Mycobacterium Avium. There was satisfactory
      progress following bipolar oesophageal isolation, nutrition via a jejunostomy and
      antibiotic therapy with co-amoxiclav. Healing of the fistulae after 11 months
      allowed surgical restoration of oesophago-gastric continuity. CONCLUSION: As with
      other bacteria, HIV can modify the clinical spectrum of nocardiosis.

PMID- 15260051
TI  - [Efficacy of gefitinib (Iressa) in the treatment of an inoperable
      bronchioloalveolar cell carcinoma].
AB  - INTRODUCTION: Bronchioloalveolar cell carcinoma (BAC) is a rare bronchial tumour.
      At present the only curative treatment is surgery and inoperable cases are often
      resistant to radio and chemotherapy. CASE REPORT: A 76 year old woman was treated
      surgically for a BAC, stage T2N0M0. Three months later she presented with cough
      and dyspnoea. Investigation revealed recurrence of the disease with bilateral
      pulmonarymetastases. She then received two courses of chemotherapy leading, at
      best, to stabilisation of the disease. At that time the treatment decision was
      simple observation. Six months later when there was progression of the bilateral
      lesions treatment was initiated with gefitinib 250 mg daily. This lead to rapid
      improvement in the clinical symptoms and the chest x-ray and CT scan showed
      evidence of a partial response that persisted one year after the beginning of
      treatment. CONCLUSION: This observation describes the effect of gefitinib in the
      treatment of inoperable BAC for which there is, at present, no effective therapy.

PMID- 15260052
TI  - [Persistent cough in a saxophone player].

PMID- 15260053
TI  - [Should systemic steroids be prescribed for acute exacerbations of COPD, or
      not?].

PMID- 15260054
TI  - [Usefulness of an environmental advisor in a case of invasive pulmonary
      aspergillosis].

PMID- 15260055
TI  - [Diagnosis and staging of lung cancer (2003 update)].

PMID- 15260056
TI  - [Treatment of small cell lung cancer (2003 update)].

PMID- 15260057
TI  - [Treatment of non-small cell lung cancer (2003 update)].

PMID- 15260058
TI  - [Malignant pleural mesothelioma (2003 update)].

PMID- 15260059
TI  - [Pleural metastasis (2003 update)].

PMID- 15260060
TI  - [Clinical practice guideline: drug therapy for corticosteroid-induced
      osteoporosis].

PMID- 15260061
TI  - [Exposure to house respiratory allergens: news for the clinician].

PMID- 15260062
TI  - [Asthma-obesity relationships: what may be concluded in practice?].

PMID- 15260063
TI  - [Difficult asthma: what are the main obstacles?].

PMID- 15260064
TI  - [Churg-Strauss syndrome induced by anti-leukotrienes: fact or fiction?].

PMID- 15260065
TI  - [Respiratory rehabilitation: which are the small ways that work?].

PMID- 15260066
TI  - [Common interstitial pneumopathy, desquamative interstitial pneumopathy, non
      specific interstitial pneumopathy: where is the difference?].

PMID- 15260067
TI  - [Base pulmonary fibrosis associated with summit emphysema: a new clinical
      entity?].

PMID- 15260068
TI  - [Is there still a role for pulmonary biopsy in idiopathic interstitial
      pneumopathy?].

PMID- 15260069
TI  - [Idiopathic pulmonary fibrosis: should corticoids still be used? Which
      immunosuppressive agent, for how long?].

PMID- 15260070
TI  - [Can mandibular advancement prosthesis be used in the treatment of sleep apnea
      syndrome? Arguments for].

PMID- 15260071
TI  - [Can mandibular advancement prosthesis be used in the treatment of sleep apnea
      syndrome? Arguments against].

PMID- 15260072
TI  - [Should the sleep of a snoring child be explored?].

PMID- 15260073
TI  - [Relationships between arterial hypertension and sleep apnea syndrome: what may
      be concluded in practice?].

PMID- 15260074
TI  - [Central apnea in heart failure: is this frequent? should it be treated?].

PMID- 15260075
TI  - [Solitary pulmonary nodule without diagnosis: is it indication for F-18-fluoro
      deoxyglucose scintigraphy (18-FDG-PET-SCAN)?].

PMID- 15260076
TI  - [Excision of lung cancer in "limit" VEMS patients: which preoperative assessment?
      How far can one go?].

PMID- 15260077
TI  - [Surveillance of surgically treated lung cancer: why, when, how?].

PMID- 15260078
TI  - [Non-small cell multifocal lung cancer: should it be surgically treated or not?].

PMID- 15260079
TI  - Research on fear/anxiety.

PMID- 15260081
TI  - Insulin resistance in Japanese adolescents with type 2 diabetes mellitus.
AB  - An oral glucose tolerance test (O-GTT) was conducted in 22 patients with type 2
      diabetes mellitus whose ages at onset were less than 18 years old. They were
      classified into 2 groups, obese and non-obese at onset, and insulin secretory
      function was compared with that of a non-obese healthy group. The results show
      that, in the group of obese subjects with type 2 diabetes mellitus, both values
      of fasting IRI and sigmaIRI were significantly higher than those in the healthy
      group. In the non-obese adolescent group with type 2 diabetes mellitus, both
      values of fasting IRI and sigmaIRI were also significantly higher than those in
      the healthy group, although the difference was not as prominent as in the obese
      subjects with type 2 diabetes mellitus. It was revealed that insulin resistance
      is present not only in obese adolescents with type 2 diabetes mellitus, but also
      in non-obese adolescents with type 2 diabetes mellitus.

PMID- 15260080
TI  - Indexes of insulin resistance using the oral glucose tolerance test (O-GTT) in
      Japanese children and adolescents.
AB  - An oral glucose tolerance test (O-GTT) was conducted in 96 non-obese healthy
      children (7 to approximately 11 years old) and adolescents (12 to approximately
      16 years old) to obtain the index of insulin resistance from the insulin (IRI)
      and C-peptide (CPR) values of fasting. 2-hour postload conditions and the sigma
      values, and the homeostasis model assessment ratio (HOMA-R) by assuming the value
      of the mean + 2SD to be the upper limit of the normal value for each clinical
      variable. The results show that the adolescents, whose insulin resistance is
      thought to increase, showed higher IRI and CPR values of the 2-hour postload
      condition and sigma values compared to those of the children, but there were no
      differences between the 2 age groups in the values of the fasting condition, as
      well as in the HOMA-R values which were calculated from the fasting values. These
      findings indicate that there is a limitation in using fasting values to judge
      insulin resistance. Instead, using the 2-hour postload values and/or the sigma
      values is more appropriate.

PMID- 15260082
TI  - Effect of low-dose ketamine on redistribution hypothermia during spinal
      anesthesia sedated by propofol.
AB  - Mild hypothermia is a common complication during spinal anesthesia and may induce
      a serious adverse outcome. We investigated the effect of low-dose ketamine
      infusion on the core temperature during spinal anesthesia sedated by propofol
      infusion. Twenty patients who were scheduled to undergo spinal anesthesia were
      assigned to one of two groups: after intrathecal injection of bupivacaine,
      patients who received infusion of ketamine (0.3 mg/kg/hr) and propofol (initial
      rate of 10 mg/kg/hr) (KP group), and patients who received infusion of placebo
      (saline) and propofol (initial rate of 10 mg/kg/hr) (P group). The rate of
      propofol administration was reduced as much as possible while maintaining
      sedation with an OAA/S score of 3 or below. The core temperature, forearm
      temperature, and fingertip temperature were recorded before spinal anesthesia,
      and just before (baseline) and 15, 30, 45, and 60 minutes after the start of
      propofol administration. The core temperature, reduction in core temperature from
      baseline (delta CT), and forearm-fingertip temperature gradient were compared
      between the two groups. In the P group, the core temperature linearly decreased
      over time. The core temperature at 30, 45, and 60 minutes was significantly
      higher in the KP group than in the P group (36.3 +/- 0.2 and 35.9 +/- 0.3, at 60
      minutes, mean +/- SD, p < 0.05). The delta CT at 15, 30, 45, and 60 minutes was
      significantly smaller in the KP group than in the P group. There were no
      significant differences in the forearm-fingertip temperature gradient between the
      two groups over the study period. In conclusion, low-dose ketamine administration
      may confer thermoprotection during spinal anesthesia sedated by propofol.

PMID- 15260083
TI  - Mutational analysis of the macrophage scavenger receptor 1 (MSR1) gene in primary
      lung cancer.
AB  - Allelic deletion at chromosome 8p21-25 is an early and frequent event in the
      carcinogenesis and development of various cancers. To facilitate investigation of
      alterations of the macrophage scavenger receptor 1 (MSR1), which is located on
      8p22, and to determine the role of this gene in human carcinogenesis and tumor
      progression, we determined intronic primers designed to amplify the coding
      region. Since frequent deletion of 8p21-23 has been previously reported in lung
      cancer, we searched for mutations throughout the coding sequence of the MSR1 gene
      within a panel of genomic DNA samples obtained from 30 primary lung cancers. Our
      approach, which involved polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) analysis and direct DNA sequencing, revealed nucleotide
      variants of the MSR1 gene in only one of the 30 cases examined, with this sample
      displaying both a 6 bp deletion and a thymine-to-cytosine substitution, the
      latter occurring within intron 7. The 6 bp deletion was located at a DNA
      microsatellite region and the thymine-to-cytosine substitution seemed to be a
      polymorphism. These results suggest that the MSR1 gene is not commonly mutated in
      lung cancer and not important in susceptibility to lung cancer. Further studies
      may focus on alternative mechanisms through which the MSR1 gene might be
      inactivated, such as aberrant DNA methylation, and/or pursue analyses of other
      genes on 8p21-23 for mutational events. Nevertheless, the panel of intronic PCR
      primer pair sequences presented here will facilitate future studies to determine
      the full spectrum and frequency of genetic events that may affect
      expression/activity of the MSR1 gene in human tumors.

PMID- 15260084
TI  - Effect of oral tizanidine on local-anesthetic infiltration pain during epidural
      catheterization.
AB  - PURPOSE: Tizanidine is a clonidine derivative and has the same effects, such as
      sedation, anxiolysis and analgesic response. We evaluated the effect of
      tizanidine on infiltration pain during epidural catheterization. METHODS: Forty
      patients scheduled to undergo epidural anesthesia in elective surgery were
      randomly allocated into two groups. The control group received placebo 60 minutes
      before arrival in the operating room, and the tizanidine group received 3 mg of
      oral tizanidine as premedication 60 minutes before arrival in the operating room.
      Every patient was measured heart rate and blood pressure before receiving placebo
      or premedication and after arrival in the operating room. After an epidural
      catheter was indwelled, the patients were questioned about the infiltrating pain
      of local anesthetic, and the degree was assessed by means of visual analog scale
      score (VAS score, 0 to approximately 100 mm). RESULTS: Blood pressure in the
      operating room was significantly attenuated in the tizanidine group compared to
      the control group (148 +/- 21 mmHg vs 130 +/- 15 mmHg). Heart rate was not
      significantly different between the two groups. Rate-pressure product was
      significantly lower in the tizanidine group (11282 +/- 2960 vs 9592 +/- 2632).
      VAS score in the tizanidine group was significantly lower than that in the
      control group (P <0.001). CONCLUSION: It was possible to reduce the infiltration
      pain of local anesthetic during epidural catheterization by oral administration
      of 3 mg of tizanidine as premedication. Blood pressure and rate-pressure product
      in the operating room were also attenuated by receiving tizanidine. Therefore, we
      recommend premedication with tizanidine for patients undergoing epidural
      catheterization.

PMID- 15260085
TI  - Subcutaneous emphysema after tonsillectomy: a case report.
AB  - We experienced a case of a subcutaneous emphysema after tonsillectomy. The
      patient, a 24-year-old man, complained of a recurrent sore throat and was
      diagnosed as having chronic tonsillitis. Pre-operative general examinations
      revealed no abnormalities. The operation was carried out under general
      anesthesia. The adhesions between the tonsils and the surrounding tissues were
      moderate. The bi-lateral tonsils were easily removed. The recovery period was
      uneventful. On the next morning, marked swelling of the left cheek and
      submandibular area was noted. On palpation, there was a characteristic
      crepitation and softness in these areas. The X-ray examination revealed
      subcutaneous emphysema. There was no finding of airway obstruction. We diagnosed
      him as having a subcutaneous emphysema and administered antibiotics for 5 days.
      From clinical findings, the subcutaneous emphysema was thought to be caused by
      surgical rather than anesthetic factors. The subcutaneous emphysema gradually
      disappeared. One year after the tonsillectomy, the patient is under observation
      as an outpatient and is free from any abnormal symptoms. To avoid this kind of
      complication, we should pay attention to carefully separate the tonsil from its
      fossa and to make appropriate selection of surgical equipments.

PMID- 15260086
TI  - High efficacy of imatinib for recurrent gastrointestinal stromal tumor in the
      jejunum: a case report.
AB  - Gastrointestinal stromal tumor is a mesenchymal tumor of the digestive tract.
      Although there used to be no effective therapy for the tumor, there have been
      many recent reports on the efficacy of imatinib. We report on a 53-year-old
      female patient with a primary tumor of the jejunum who underwent 3 operations. As
      the tumor could not be removed at the 3rd operation, she was given imatinib
      orally. Results showed significant reduction ratios of the tumor area (83.0%) and
      volume (92.2%) at 18 months after starting imatinib administration. Also, the
      mean reduction ratios of the tumor area and volume per month (%/M) after starting
      imatinib treatment showed remarkable results, especially during the initial 3
      weeks: 53.9%/M and 49.5%/M, respectively. Whether imatinib is the first choice of
      treatment for GIST or not, and what is the appropriate dose and period should be
      resolved.

PMID- 15260087
TI  - Interaction between iopamidol and gadopentetate dimeglumine: an in-vitro
      experimental study of direct mixing.
AB  - OBJECTIVE: To determine whether or not there is any interaction between iopamidol
      and gadopentetate dimeglumine (Gd-DTPA) in test tubes using the direct mixing
      manner. MATERIALS AND METHODS: The test solution was prepared by mixing iopamidol
      (Iopamiron 300) and Gd-DTPA (Magnevist) at a ratio of 1:1. The color, viscosity,
      and pH of the mixed solutions were assessed immediately after mixing and 1,3,6,
      and 24 hours after mixing. The concentration of aromatic primary amines, content
      of iopamidol, concentration of free iodine ion, and content of Gd-DTPA in the
      mixed solution were determined, and the presence or absence of spots, other than
      those resulting from iopamidol and Gd-DTPA, was determined using thin layer
      chromatography. These tests were carried out immediately, and 24 hours after
      mixing. Using iopamidol alone and Gd-DTPA alone as controls, the same items were
      examined. RESULTS: There was no significant change in the appearance or pH of the
      mixed iopamidol and Gd-DTPA solution immediately and 1, 3, 6, and 24 hours after
      direct mixing. The study of iopamidol alone or Gd-DTPA alone showed no apparently
      abnormal values or findings. CONCLUSION: The direct mixing of iopamidol and Gd
      DTPA in a test tube results in no significant interaction.

PMID- 15260088
TI  - Long-term follow-up after interbody fusion of the cervical spine.
AB  - The aim of this work was to add to the body of data on the frequency and severity
      of degenerative radiographic findings at adjacent levels after anterior cervical
      interbody fusion and on their clinical impact and to contribute to the insights
      about their pathogenesis. One hundred eighty patients who were treated by
      anterior cervical interbody fusion and who had a follow-up of >60 months were
      clinically and radiologically examined by independent investigators. For all
      patients, the long-term Odom score was compared with the score as obtained 6
      weeks after surgery. For myelopathic cases, both the late Nurick and the Odom
      score were compared with the initial postoperative situation. For the adjacent
      disc levels, a radiologic "degeneration score" was defined and assessed both
      initially and at long-term follow-up. At late follow-up after anterior cervical
      interbody fusion, additional radiologic degeneration at the adjacent disc levels
      was found in 92% of the cases, often reflecting a clinical deterioration. The
      severity of this additional degeneration correlated with the time interval since
      surgery. The similarity of progression to degeneration between younger trauma
      patients and older nontrauma patients suggests that both the biomechanical impact
      of the interbody fusion and the natural progression of pre-existing degenerative
      disease act as triggering factors for adjacent level degeneration.

PMID- 15260089
TI  - Conjoined lumbar nerve roots: a frequently underappreciated congenital
      abnormality.
AB  - Nerve root anomalies are frequently underrecognized on advanced imaging studies
      and may account for some percentage of failed spinal surgical procedures. The
      conjoined nerve root represents the most common nerve root anomaly. It is a well
      known cause of false-positive readings for bulging and herniated disks in
      patients with purely axial neuroimaging studies. A retrospective evaluation of
      consecutive microsurgical lumbar diskectomies in 80 patients during a 5-year
      period was undertaken. A total of four patients (5%) were found intraoperatively
      to have evidence of a conjoined nerve root by the classification of Neidre. None
      was diagnosed preoperatively. Coronal magnetic resonance imaging offers the best
      means of visualizing a conjoined nerve root. The chance for a successful
      operation can be significantly enhanced if the surgeon is prepared to encounter
      this pathology.

PMID- 15260090
TI  - Cervical laminoplasty for subaxial lesion in rheumatoid arthritis.
AB  - Expansive laminoplasty of the cervical spine was performed for 15 patients with
      subaxial lesion (SAL) in rheumatoid arthritis (RA) with or without symptomatic
      occipitocervical pathology. Clinical results were satisfactory, and radiographic
      evaluation revealed that the range of movement of the cervical spine decreased to
      56.3%, spinal alignment was well preserved, and intervertebral slipping advanced
      only slightly. Therefore, expansive laminoplasty is shown to be clinically
      effective in decompressing the subaxial spinal cord without the need for fusion
      of this region, yet it avoids exacerbating or creating significant instability.
      We found that it can serve as a useful procedure for treating spinal cord
      compression caused by SAL in RA. For patients with upper cervical instability,
      laminoplasty with upper cervical fusion appears to be an effective option. In a
      case in which kyphosis was observed preoperatively, its deformity became worse
      after laminoplasty. Thus, it may be advisable to consider subaxial fusion in such
      cases.

PMID- 15260091
TI  - Morphologic evaluation of cervical spine anatomy with computed tomography:
      anterior cervical plate fixation considerations.
AB  - The computed tomography (CT) studies of the cervical spine from 50 males and 50
      females were reviewed to provide morphometric data on a variety of anatomic
      parameters relevant to anterior cervical reconstruction and fixation.
      Measurements were made of the vertebral body width and midsagittal
      anteroposterior (AP) diameter and the distance between the medial borders of the
      longus coli muscles. Distances between adjacent endplates were also measured,
      both at their midpoint and at the anterior margin. Widths of the vertebral bodies
      measure 24.6 +/- 2.4 and 23.0 +/- 2.4 mm in males and females, respectively, with
      the narrowest measuring 17 and 14, respectively. The average midsagittal AP
      diameter of each vertebral body in males was approximately 17-18 mm, with the
      smallest AP diameter measured to be 13 mm. The average midsagittal AP diameter of
      each vertebral body in females was approximately 15-16 mm, with the smallest
      being 10 mm. CT scanning provides excellent osseous detail for the measurement of
      such parameters, and with its widespread use in the evaluation of cervical
      disorders, large numbers of patients can be reviewed.

PMID- 15260092
TI  - Long-term clinical manifestations of retained bullet fragments within the
      intervertebral disk space.
AB  - A retrospective review of 12 patients who were victims of penetrating trauma with
      a bullet or bullet fragments lodged within the intervertebral disk space was
      conducted. The objective of the review was to evaluate the potential systemic
      effects of lead resorption at long-term follow-up. Literature regarding the
      potential for lead toxicity due to retained bullet fragments within the
      intervertebral disk space is lacking. Between January 1969 and June 1993, a total
      of 238 patients with a gunshot wound to the spine were identified. Twelve of the
      238 were found to have a bullet or bullet fragments within the intervertebral
      disk space. All patients were fully screened for evidence of plumbism. The
      average age at time of gunshot injury was 35.8 years; the average time for follow
      up was 7.8 years. One of the 12 patients showed clinical evidence of plumbism.
      The patient subsequently underwent a partial laminectomy and diskectomy with
      excision of the bullet fragments. The patient's complaints, specific for
      plumbism, resolved 2 months postoperatively. We conclude that patients with
      retained lead-based bullet fragments in the intervertebral disk should be
      educated about the rare potential for plumbism due to partial bullet fragment
      resorption and that long-term observation for this disorder is recommended.

PMID- 15260093
TI  - Histopathologic effects of discitis on neural tissues: an experimental study.
AB  - To determine the cause of neurologic symptoms and signs seen in discitis, the
      neural histopathologic effects of discitis were investigated in an experimental
      study carried out on rats. Groups of seven rats each had their intervertebral
      discs inoculated with either Staphylococcus aureus, Klebsiella pneumoniae,
      Pseudomonas aeruginosa, or a control solution. Histopathologic examinations of
      the spinal cord and nerve roots were performed after 3 weeks. On histopathologic
      examination, vacuolar myelopathy in the spinal cord and vacuolar neuropathy
      within the nerve roots near the junction with the spinal cord were found. The
      severity and form of vacuolar myelopathy varied according to the bacteria used
      for inoculation. The myelopathy and neuropathy seen in this rat model of
      bacterial discitis might be the result of an immunologic mechanism and could be
      responsible for the neurologic signs and symptoms of discitis in patients.

PMID- 15260094
TI  - Acinetobacter baumanii meningitis: a rare complication of incidental durotomy.
AB  - Despite the frequency of dural tears in spinal surgery, meningitis is a rare
      complication reported to occur with a frequency of 0.18%. To the best of our
      knowledge, no case of Acinetobacter baumanii meningitis has been reported in the
      literature after a dural tear secondary to lumbar spine discectomy. This case
      highlights the importance of repairing all dural tears and commencing antibiotics
      that cover uncommon bacteria in those who develop symptoms of meningitis in this
      setting.

PMID- 15260095
TI  - Cervical spine loading characteristics in a cadaveric C5 corpectomy model using a
      static and dynamic plate.
AB  - Anterior plates are used to increase the initial stability of anterior cervical
      spine fusions; however, plating has been suggested to cause graft stress
      shielding, leading to reduced fusion rates. The objectives of this study were to
      quantify the effects of graft size and plating (static versus dynamic) and the
      role of the posterior elements on load transmission in anterior cervical fusion.
      A C5 corpectomy was performed on six human cervical spines (C3-C7). An
      instrumented height-adjustable graft and dynamic cervical plate were used to
      measure axial load transmission. Each specimen underwent axial compressive
      testing with dynamic and static plate configurations, optimal and undersized
      graft heights, and posterior elements intact and removed. Dynamic plating allowed
      significantly more load transmission by the graft, particularly in the undersized
      graft configuration. The posterior elements play a significant role in load
      transmission.

PMID- 15260096
TI  - Probabilistic design analysis of the influence of material property on the human
      cervical spine.
AB  - Studies reported previously in the literature have described the importance of
      material variation on the cervical responses and have examined some effects by
      varying the material properties, but there is no systematic approach using
      statistical methods to understand the influence of material variation on a
      cervical spine model under a full range of loading conditions, especially under
      compression and anterior and posterior shear. A probabilistic design system based
      on Monte Carlo simulation methods using Latin hypercube sampling techniques is
      used to analyze the material sensitivity of a C4-C6 cervical spine model
      involving 13 uncertain input parameters on the biomechanical responses and disc
      annulus stresses under compression, anterior shear, posterior shear, flexion,
      extension, lateral bending, and axial rotation. The loading types and range of
      values were as follows: compression, 0-1 mm; anterior shear, 0-2 mm; posterior
      shear, 0-3.5 mm; flexion, extension, lateral bending, and axial rotation. 0-1.8
      Nm with 73.6-N preload. For each case, the load-deflection and key stress values
      at various spinal components were captured after each load step. The model was
      also validated under the same conditions. The minimum and maximum predicted
      responses were within the range of the experimental data. Ignoring compression
      loading, the combined effects on the biomechanical responses of the cervical
      ligaments under the remaining loads are enormous. Their total impacts are almost
      equal to or slightly less than the influence of disc annulus. Results show that
      the fiber mechanical properties did not have a significant effect on the
      compressive stiffness. This study reveals important features that help us
      identify the critical input parameters and enable us to reduce the development
      time of a patient-specific biomechanical model.

PMID- 15260097
TI  - Analysis of the effect of lumbar spine fusion on the superior adjacent
      intervertebral disk in the presence of disk degeneration, using the three
      dimensional finite element method.
AB  - The purpose of this study was to analyze the effect of lumbar spine fusion on the
      superior adjacent intervertebral disk in the context of disk degeneration, using
      a nonlinear three-dimensional finite element method. Detailed L3-L5 motion
      segment models of normal and degenerated intervertebral disks were developed. In
      fusion models, L4-L5 was fixed by either posterolateral fusion or posterior
      lumbar interbody fusion (PLIF). Various loading conditions such as compression
      loading, compression loading plus flexion moment loading, or compression loading
      plus extension moment loading were applied to study the corresponding stress.
      Tresca stress on the posterolateral part of intervertebral annulus fiber and von
      Mises stress on the vertebral endplate (the superior and inferior sides of L3 and
      L4) were reduced in all degenerated disk models compared with the normal disk
      models. The PLIF model showed an increase in the percentage change of stress on
      the vertebral endplate and on the intervertebral annulus fibrosus when flexion
      and extension moment loadings were applied. This finding suggests that surgeons
      should consider the risk of exacerbating degeneration of intervertebral disks by
      undertaking lumbar spine fusion, when degeneration is found in intervertebral
      disks adjacent to vertebrae requiring fusion.

PMID- 15260098
TI  - Kinematics of the thoracic T10-T11 motion segment: locus of instantaneous axes of
      rotation in flexion and extension.
AB  - The purpose of this study was to determine the locations and loci of
      instantaneous axes of rotation (IARs) of the T10-T11 motion segment in flexion
      and extension. An anatomically accurate three-dimensional model of thoracic T10
      T11 functional spinal unit (FSU) was developed and validated against published
      experimental data under flexion, extension, lateral bending, and axial rotation
      loading configurations. The validated model was exercised under six load
      configurations that produced motions only in the sagittal plane to characterize
      the loci of IARs for flexion and extension. The IARs for both flexion and
      extension under these six load types were directly below the geometric center of
      the moving vertebra, and all the loci of IARs were tracked superoanteriorly for
      flexion and inferoposteriorly for extension with rotation. These findings may
      offer an insight to better understanding of the kinematics of the human thoracic
      spine and provide clinically relevant information for the evaluation of spinal
      stability and implant device functionality.

PMID- 15260099
TI  - A biomechanical study of lumbar fusion based on a three-dimensional nonlinear
      finite element method.
AB  - Biomechanical analyses under compression, flexion, and extension loading were
      performed to evaluate the stability of interbody, posterolateral, posterior, and
      facet fusions using a nonlinear three-dimensional finite element method. The
      effects of facet fusion on other lumbar fusions were also examined. A three
      dimensional L4-L5 motion segment model was developed that took into consideration
      the material nonlinearities of ligaments and annular fibers and the contact
      nonlinearities of facet joints. Of all models of fusion, maximum rigidity was
      obtained in the interbody fusion model. In the posterolateral, posterior, and
      facet fusion models under compression, axial displacement and flexion rotation
      were induced. In combination with facet fusion, the interbody, posterolateral,
      and posterior fusion models demonstrated a decrease in axial displacement of
      about 6%, 1%, and 5%, respectively, under compression and a decrease in rotation
      angle of about 22%, 12%, and 48%, respectively, under flexion-extension loading.
      Stress concentration moved principally toward the fusion site, indicating
      increased load transfer across the fusion mass. Our findings suggest that a more
      solid fixation can be expected from lumbar fusion--especially in posterior fusion
      -if facet fusion is performed.

PMID- 15260100
TI  - The treatment of far-out foraminal stenosis below a lumbosacral transitional
      vertebra: a report of two cases.
AB  - Far-out foraminal stenosis with radiculopathy caused by bony spur formation
      secondary to anomalous articulation between the transverse process and the sacral
      ala is rarely reported. We report two cases of unilateral far-out foraminal
      entrapment of the L5 spinal nerve below a transitional vertebra, with a review of
      the literature. The objective of this work was to describe the management of a
      rare far-out foraminal stenosis below a transitional vertebra and to evaluate the
      surgical and conservative procedures and results. In a previous article,
      decompression was performed through an anterior approach. However, we report no
      difficulty with decompression using a posterior approach for one patient. The
      diagnosis was confirmed with computed tomography, magnetic resonance imaging, and
      selective radiculography. First, selective nerve root blocks were performed in
      two cases for the purpose of nonoperative treatment. After failure of
      conservative treatment with selective nerve root block, one patient underwent
      posterior decompression by resection of the bony spur using a posterior approach.
      One patient obtained good relief of radicular pain with only selective nerve root
      block. The other patient obtained good relief of radicular pain after posterior
      decompression was performed. Posterior decompression through the posterior
      approach is an easy, safe, and useful treatment for radicular pain caused by an
      L5 nerve far-out foraminal stenosis below a transitional vertebra when
      conservative treatments have failed to obtain good relief of radicular pain.

PMID- 15260101
TI  - Posterior C2 fixation using bilateral, crossing C2 laminar screws: case series
      and technical note.
AB  - Rigid screw fixation of the axis, for either atlantoaxial fixation or for
      incorporation of C2 into subaxial cervical constructs, provides significant
      stability and excellent long-term fusion results but remains technically
      demanding due to the danger of injury to the vertebral artery. Anatomic
      variability of the foramen transversarium in the body of the axis can preclude
      safe transarticular C1-C2 screw placement in up to 20% of patients. Although more
      recent methods of C2 screw fixation with pedicle screws allow safer fixation in a
      higher number of patients, there remains a significant risk to the vertebral
      artery with C2 pedicle screw placement. The author describes a novel technique of
      C2 rigid screw fixation using bilateral, crossing C2 laminar screws, not
      previously reported in the literature, which does not place the vertebral artery
      at risk during C2 fixation. This technique has been successfully used by the
      author in cases of craniocervical and atlantoaxial fixation as well as for
      incorporation of C2 into subaxial fixations. The technique is illustrated, and
      the author's initial experience in treating 10 patients with crossing, bilateral
      C2 aminar screws for indications of trauma, neoplasm, pseudarthrosis, and
      degenerative disease is reviewed. The possible advantages of C2 fixation with C2
      laminar screws are discussed.

PMID- 15260102
TI  - T12-L1 telescoped chronic dislocation treated by en bloc one-piece spondylectomy
      and spine shortening.
AB  - The author presents a case in which a severe chronic thoracolumbar kyphotic
      posttraumatic deformity was corrected by a one-block spondylectomy with spine
      shortening, using a posterior approach. A 19-year-old paraplegic woman was
      admitted with a chronic deformity of the thoracolumbar spine due to a telescoped
      posterior dislocation of L1 on T12, which had occurred 8 months earlier. Single
      reduction by axial traction was impossible. Surgical correction was achieved by
      means of a total, one-block, L1 spondylectomy and end-to-end apposition of the
      T12 inferior platform onto the L2 superior platform. This was performed through a
      posterior approach. The reduction was fixed by a pedicular instrumentation
      extended from T10 to L4. To our knowledge, this is the first documented case in
      which the spondylectomy was performed in a single block including the vertebral
      body and posterior arch in the same piece. Five years following surgery, the
      clinical result is excellent with complete correction of the deformity and solid
      interbody vertebral fusion. The complete transection of the spinal cord permitted
      this aggressive approach, which would have not been possible in other types of
      pathology.

PMID- 15260103
TI  - Molecular basis of X-linked non-specific mental retardation.
AB  - Mental retardation (MR) is a common disorder, affecting 1-3% of the total
      population. This condition results from failure to develop cognitive abilities
      and intelligence level appropriate for the age group. Mental retardation is
      basically a clinically as well as etiologically heterogeneous type of condition
      and both genetic and non-genetic factors have been found to be involved. There
      are more than 1000 entries in Online Mendelian Inheritance in Man (OMIM) database
      under the name of mental retardation. In recent years 15 genes for X linked non
      specific mental retardation have been identified which provide important clues
      regarding molecular and cellular processes involved in signal transduction
      cascade in central nervous system. Recent advancements in identification and
      characterization of X-linked non-specific mental retardation genes have been
      discussed in this review. Understanding of the molecular pathways of disease
      causing genes would be helpful in developing effective therapeutic approaches for
      mental retardation.

PMID- 15260104
TI  - Immune haemolymph proteins in response to bacterial infection and identification
      of a putative bacteria binding protein in malaria vector Anopheles stephensi.
AB  - Induction of haemolymph proteins in mosquito A. stephensi due to wounding or
      bacterial infection (E. coli) was analyzed using SDS-PAGE. Wounding response of
      pupa revealed subsequent induction of two polypeptides (21 and 74 kDa). Two other
      polypeptides (44 and 57 kDa) were induced commonly in both pupa and adult female
      haemolymph upon bacterial infection. In vitro binding assay revealed
      identification of 44 kDa, a putative bacterial binding protein, a more relevant
      protein for further elucidation of molecular mechanism involved in host parasite
      interactions.

PMID- 15260105
TI  - Lung specific stealth liposomes as antitubercular drug carriers in guinea pigs.
AB  - The problem of patient non-compliance in the management of tuberculosis (TB) can
      be overcome by reducing the dosing frequency of antitubercular drugs (ATD)
      employing drug carriers. This study reports on the intravenous (iv)
      administration of lung specific stealth liposomes encapsulating ATD (rifampicin
      and isoniazid in combination) to guinea pigs and the detailed
      pharmacokinetic/chemotherapeutic studies. Following a single iv administration of
      liposomal drugs, the latter were found to exhibit sustained therapeutic levels in
      plasma for 96-168 hr with half-lives of 24-70 hr, mean residence time (MRT) of 35
      81 hr and organ drug levels up to day 7. The relative bioavailability (as
      compared to oral free drugs) was increased by 5.4-8.9 folds, whereas the absolute
      bioavailability (as compared to iv free drugs) was increased by 2.9-4.2 folds.
      Weekly therapy with liposomal ATD for 6 weeks produced equivalent clearance of
      Mycobacterium tuberculosis from organs as did daily therapy with oral free drugs.
      Hence, intravenous liposomal ATD offer the therapeutic advantage of reducing the
      dosing frequency and improving the patient compliance in the management of TB.

PMID- 15260106
TI  - Modulatory effect of diclofenac on antispasmodic effect of pitofenone in
      cholinergic spasm.
AB  - Biliary, ureteric and intestinal colic are extremely common clinical conditions
      associated with smooth muscle spasm. In the present study, antispasmodic activity
      was carried out against acetylcholine (10-640 ng/ml)-induced contractions on
      guinea pig ileum. Acetylcholine (10-640 ng/ml) induced concentration-dependent
      contraction of smooth muscle. Diclofenac, in varying concentration (9.4 x 10(-5)
      mol/l and 14.1 x 10(-5) mol/l) shifted the concentration response curve of
      acetylcholine to the right without suppressing the maximal response. However, in
      higher concentration diclofenac (18.9 x 10(-5) mol/l) blocked the response in an
      unsurmountable fashion. Further, analgin (11.09 x 10(-5), 16.63 x 10(-5) and
      22.18 x 10(-5) mol/l) in equimolar concentrations did not alter the concentration
      response curve of acetylcholine, but in higher concentration analgin (44.36 x 10(
      5) mol/l) also blocked the response in an unsurmountable fashion. Pitofenone (2.5
      x 10(-6) mol/l) also, shifted the concentration response curve of acetylcholine
      to right in a parallel fashion with no change in maximal response. The present
      study confirms the potent antispasmodic activity of diclofenac-pitofenone
      combination in comparison to analgin-pitofenone in molar equivalent concentration
      (in comparison to diclofenac) against acetylcholine-induced contractions of
      guinea pig ileum.

PMID- 15260107
TI  - Comparative effectiveness of CaNa3DTPA and tiron along with alpha-tocopherol
      against beryllium-induced biochemical alterations in rats.
AB  - The therapeutic efficacy of chelating agents CaNa3DTPA (calcium trisodium
      diethylene triamine penta acetic acid) and Tiron (sodium-4,5-dihydroxy-1,3
      benzene disulphonate) with and without antioxidant, alpha-Tocopherol was
      evaluated in the treatment of beryllium-induced toxicity in female albino rats.
      The animals were exposed to beryllium (as beryllium nitrate) at a dose of 1 mg/kg
      (ip) once a day for 28 consecutive days followed by chelation therapy by
      CaNa3DTPA (0.1 mM/kg, ip) and Tiron (471 mg/kg, ip) with and without alpha
      Tocopherol (25 mg/kg, orally) for 5 consecutive days after toxicant
      administration. Tissue biochemistry revealed severe alterations in liver and
      kidney. A significant fall in total protein and glycogen contents, alkaline
      phosphatase, adenosine tri-phosphatase and succinic dehydrogenase level was
      noticed. On the contrary, an elevation in acid phosphatase was recorded. The
      significant rise in hepatic lipid peroxidation and decreased level of hepatic
      reduced glutathione showed toxicity due to beryllium. CaNa3DTPA with alpha
      Tocopherol showed moderate therapeutic efficacy while Tiron in combination with
      alpha-Tocopherol exerted statistically more beneficial effects to reverse
      biochemical alterations in different variables altered due to beryllium
      intoxication.

PMID- 15260108
TI  - Caffeine in tea plants [Camellia sinensis (L) O. Kuntze]: in situ lowering by
      Bacillus licheniformis (Weigmann) Chester.
AB  - Tea plants (Camellia sinensis) contain 5-6% caffeine that is responsible for the
      stimulating effect of the beverage. As the tolerance to caffeine varies among
      individuals, low caffeine tea would be an ideal alternative. While assessing the
      potential of a few selected bacteria-Bacillus licheniformis, B. subtilis and B.
      firmus, to multiply on nutrient medium supplemented with glucose (5%) and tea
      leaf extract (2%), it was observed that only B. licheniformis could proliferate
      on this medium. Hence, B. licheniformis was used for further studies. Tea plants
      were sprayed with a suspension of B. licheniformis at a dilution of 5 x 10(8)
      CFU/ml containing 0.1% Tween 80 as surfactant. In situ lowering of caffeine from
      tea leaves was evident without affecting the quality of the other tea components.
      Further, there was no change in the morphological and physiological
      characteristics as well. It is suggested that spraying of B. licheniformis may be
      useful in yielding decaffeinated tea with good flavour and aroma.

PMID- 15260109
TI  - Influence of antiangiogenic fraction from Diogenes avarus (Heller) on fertility
      and implantation in mice.
AB  - The methanol extract isolated from hermit crab, D. avarus degenerated ovarion and
      uterine tissues in cyclic and pregnant mice, treated before and after the
      implantation. Immunohistochemical staining using CD31 and Factor VIII specific to
      endothelial cells showed reduction in microvessel density. The hormonal assay
      showed decrease in the progesterone secretion in all experimental mice.

PMID- 15260110
TI  - Antibacterial and antidiarrhoeal effects of alkaloids of Holarrhena
      antidysenterica WALL.
AB  - The alkaloids from the ethanolic extract of H. antidysenterica seeds were
      evaluated for their antibacterial activity against clinical isolates of
      enteropathogenic Escherichia coli (EPEC) in vitro, and their antidiarrhoeal
      activity on castor oil-induced diarrhoea in rats, in vivo. The plasmid DNA, whole
      cell lysate and outer membrane protein profile of a clinical isolate of EPEC was
      determined in presence of alkaloids of H. antidysenterica. The disc diffusion and
      agar well diffusion methods were used to evaluate the antibacterial efficacy. The
      alkaloids showed strong antibacterial activity against EPEC strains. In castor
      oil-induced diarrhoea, alkaloids reduced the diarrhoea with decrease in the
      number of wet faeces in pretreated rats at a dose of 200-800 mg/kg. The loss of
      plasmid DNA and suppression of high molecular weight proteins were observed on
      alkaloids treatment. Taking into account the multiple antibiotic resistance of
      EPEC, the results suggest usefulness of alkaloids of H. antidysenterica seeds as
      antibacterial and antidiarrhoeal agents.

PMID- 15260111
TI  - Effect of amaranth leaves on dimethylhydrazine-induced changes in multicomponent
      antioxidant system of rat liver.
AB  - Effect of prefeeding dehydrated amaranth (A. gangeticus) leaves at 10 and 20%
      levels on a chemical toxicant, dimethylhydrazine (DMH)-induced free radical
      stress in rat liver was evaluated. DMH-induced rise in hepatic malondialdehyde
      (MDA), was diminished by AL. AL intake resulted in a significant increase in
      hepatic glutathione (GSH). The feeding of AL at 10% level increased the hepatic
      glucose-6-phosphate dehydrogenase (G-6-PDH) activity, while that at 20% level
      increased the hepatic glutathione reductase (GSSGR) as well, in addition to G-6
      PDH. Amaranth leaves at 10 and 20% levels of feeding diminished the hepatic
      superoxide dismutase and glutathione peroxidase (GSH-Px) activities. DMH
      influenced adversely the hepatic antioxidant enzyme activities. Simultaneous
      administration of DMH and feeding of AL enhanced the DMH-induced decrease in
      hepatic GSH-Px. DMH enhanced formation of micronuclei was reverted significantly
      by AL intake. Hence, it was concluded that the consumption of AL at 20% level
      reduced DMH-induced impaired antioxidant status in rat liver.

PMID- 15260112
TI  - Antioxidant effect of curcumin in selenium induced cataract of Wistar rats.
AB  - Wistar rat pups treated with curcumin, a natural constituent of Curcuma longa
      before being administered with selenium showed no opacities in the lens. The
      lipid peroxidation, xanthine oxidase enzyme levels in the lenses of curcumin and
      selenium co-treated animals were significantly less when compared to selenium
      treated animals. The superoxidase dismutase and catalase enzyme activities of
      curcumin and selenium co-treated animal lenses showed an enhancement. Curcumin co
      treatment seems to prevent oxidative damage and found to delay the development of
      cataract.

PMID- 15260113
TI  - Relationship of fluorescence and thermal emission from isolated thylakoids under
      light stress conditions.
AB  - Simultaneous measurements of fluorescence and thermal emission have been made by
      a combined fluorescence and photoacoustic techniques on isolated thylakoids
      pretreated by a prolonged illumination of saturating light. The traces of the
      signals are used to calculate four characteristic parameters, energy storage,
      half-saturation intensity, number of photons to close reaction center, and a
      constant for quasi-equlibria between (re)oxidized and reduced quinone acceptors.
      These parameters are used to study the response of photosynthetic apparatus
      functioning under photoinhibition stress. The defense mechanism seems to possess
      an efficient cooperativity of reaction centers under stress conditions.

PMID- 15260114
TI  - Nodulation competitiveness between contrasting phage phenotypes of pigeonpea
      rhizobial strains.
AB  - Competitiveness between (I) lysogenic vs. phage-indicator strains, (II) phage
      resistant vs phage-sensitive strains, and (III) large plaque vs. small plaque
      developing strains was examined under laboratory and field conditions in order to
      study the involvement of these crucial phage sensitivity patterns in the
      competition for nodule occupancy of pigeonpea rhizobia. The phage-indicator
      strain (A039) exhibited higher competitiveness over the lysogenic strain (A025
      Sm(r)); the phage sensitive strain (IHP-195) over the phage resistant strain (IHP
      195 Sm(r)V(r)); and the large plaque developing strain (A059) over the small
      plaque developing strain (IHP195 Sm(r)) in association with pigeonpea cv. bahar
      both under laboratory and field conditions. Dual inoculation of A025 Sm(r) + A039
      and A059 + IHP195 Sm(r) (mixed in equal proportion just before treatment)
      improved the nodule occupancy by inoculant strains against native rhizobia and
      resulted into higher plant dry weight and yield as compared to their application
      as single inoculum. The phage-resistant mutant IHP195 Sm(r)V(r) showed reduced
      competitiveness against native rhizobia, compared to its parental strain. The
      dual inoculation of parental strain and phage-resistant mutant gave the same
      result as the inoculation of parental strain alone.

PMID- 15260115
TI  - Effect of auxins on berberine synthesis in cell suspension culture of Coscinium
      fenestratum (Gaertn.) Colebr--a critically endangered medicinal liana of Western
      Ghats.
AB  - Cell suspension culture of critically endangered Coscinium fenestratum was
      established from young leaf segments on WPM supplemented with auxins. Effect of
      2,4-D, IAA, IBA and NAA was examined on cell growth and berberine production.
      Berberine was synthesized and released continuously into the liquid medium.
      Presence of 2,4-D stimulated cell growth, but was not inhibitory on berberine
      synthesis. On the contrary, NAA stimulated berberine biosynthesis, but was not
      favourable for cell growth. Among the auxins tested, highest yield of berberine
      (5.79 mg/30 ml; 4.14 times to that of control) was obtained with 4 mg/l of NAA,
      while the best cell growth (214.43 mg dry wt., 1.96 times to that of control) was
      observed in the presence of 2 mg/l of 2,4-D. IAA and IBA were not favourable for
      cell growth and berberine synthesis.

PMID- 15260116
TI  - Adrenocortical involvement during diverse stress in soft-shelled turtle Lissemys
      p. punctata Bonnoterre.
AB  - Adrenocortical responses to diverse stressful situations (dehydration,
      formaldehyde treatment and salt loading) were studied in the adult female soft
      shelled turtle, Lissenmys p. punctata. Dehydration, formaldehyde treatment
      (formalin, 1%: 0.1 ml/100 g body weight daily) or salt loading (NaCl, 1%: 0.1
      ml/100 g body weight daily) treatments consecutively for 7 days caused
      hypertrophy of the adrenocortical cells with their nuclear diameter increased,
      and depletions of adrenal cholesterol and ascorbic acid concentrations followed
      by decreased acid phosphatase and alkaline phosphatase activities in turtles.
      Corticosterone levels were elevated in both the adrenal gland and serum of
      turtles after dehydration and formalin stress, but the hormone level remained
      unaltered after salt loading in turtles. The results suggest active involvement
      of adrenal cortex in stress for homeostasis in Lissemys turtles.

PMID- 15260117
TI  - Seminoma in hybrid catfish [Clarias batrachus (Linnaeus) female x Clarias
      gariepinus (Burchell) male].
AB  - Spontaneous testicular tumors, seminoma, were noticed in four male hybrid catfish
      (C. batrachus female x C. gariepinus male) after the age of two years. The
      hybrids showed massive abdominal swelling with catchectic body and free
      lobulated, encapsulated tumors (> 325 g) within the serosanguinous fluid-filled
      peritoneal cavities. The tumor cells were large and polyhedral with prominent
      centrally located nuclei. Other vital organs appeared normal. It seems to be the
      first report of seminoma in hybrid catfish and possibly of genetic cause.

PMID- 15260118
TI  - Effects of garlic (Allium sativum) extract on the heart rate, rhythm and force of
      contraction in frog: a dose-dependent study.
AB  - Garlic juice (dose equivalent to 3.3 g to 33 g garlic) mainly caused bradycardia
      in frog Rana tigerina. The disturbance in ventricular rhythm was observed prior
      to than that of atria. Rhythm was specially disturbed at higher doses causing
      bizarre pattern. Force of contraction of the heart also decreased with higher
      dose of the garlic extract. The results suggest that garlic extract has some
      beneficial effect on heart rate modulating the rate, rhythm and force of
      contraction positively but very high doses may exert non-desirable effects as
      well.

PMID- 15260119
TI  - Role of 5-hydroxytryptamine in Moringa oleifera induced potentiation of
      pentobarbitone hypnosis in albino rats.
AB  - The role of 5-hydroxytryptamine (5-HT) in pentobarbitone (PB) sleeping time,
      gross behaviour, electrical activity of the brain and serum 5-HT level was
      studied in Holtzman strain adult albino rats following treatment with M. oleifera
      (MO). MO (350mg/kg) caused inhibition of awareness, touch response, motor
      activity, righting reflex, and grip strength. It significantly increased the PB
      sleeping time, serum 5-HT level (P<0.001) and alpha-wave activity. These
      observations indicate that the aqueous extract of MO potentiated PB induced
      sleeping time and increased the alpha-wave activity through 5-HT.

PMID- 15260120
TI  - In vitro degradation of cell-wall and digestibility of cereal straws treated with
      anaerobic ruminal fungi.
AB  - Ruminal fungal isolates (Orpinomyces sp.; C-14, Piromyces sp.; C-15, Orpinomyces
      sp.; B-13 and Anaeromyces sp.; B-6), were evaluated under anoxic conditions for
      their effect on in vitro dry matter digestibility, neutral detergent fibre, acid
      detergent fibre and acid detergent lignin using rice and wheat straw as
      substrate. There was no significant effect of the fungal isolates on the
      disappearance of the substrates along with rumen liquor when compared to control.
      The doses of 10(6) cfu/ml of the isolate were found to have maximum degradation
      of straws in comparison to the doses of 10(3) cfu/ml.

PMID- 15260121
TI  - In vitro mass multiplication of Ophiorrhiza mungo Linn.
AB  - A protocol for in vitro mass multiplication of plants through seedling (shoot)
      cultures was established for Ophiorrhiza mungo. Maximum number of adventitious
      shoots per shoot culture (10.4 +/- 1.72) was initiated on MS solid medium
      supplemented with BAP (2.22 microM) after 3 weeks. Shoots were further multiplied
      (12.8 +/- 2.8) through subculture of intact shoots and reculture of nodal
      segments of aseptic shoots (6.5 +/- 0.94) in MS solid medium containing BAP (0.89
      microM). Shoot elongation (1.27 +/- 0.12 cm) was achieved in the medium
      containing GA3 (1.44 microM) in two weeks. Rooting was favoured in basal agar
      medium supplemented with IBA (12.3 microM) plus NAA (1.07 microM). The plants
      were successfully established (100%) in the pots containing sand and top soil
      (1:1) mixture in a period of two weeks.

PMID- 15260122
TI  - Analytical characterization of a sensitive radioassay for tyrosine hydroxylase
      activity in rodent striatum.
AB  - Several buffer compositions with a wide range of pH values have been reported for
      radiometric assay of tyrosine hydroxylase (TH) in biological samples. Assay
      sensitivity becomes a prime concern while analyzing TH in minute samples like
      tissue biopsies or discrete regions of rodent brain wherein lower enzyme levels
      are anticipated due to smaller sample sizes. It was therefore rationalized to
      evaluate relative affinities of three commonly used assay buffers (sodium
      phosphate, sodium acetate, and Tris-acetate) with TH enzyme activity. The impact
      of buffer pH and cofactor concentration on the sensitivity of TH assay was also
      investigated. Striata from rats or mice were homogenized, respectively, with 1.0
      or 0.5 ml of the assay buffer containing 0.5% Triton X-100. The supernatants (200
      microl) were incubated (20 min, 37 degrees C) with 0.8 microCi [3H] L-tyrosine,
      1.5 mM DL-6-methyl-5,6,7,8-tetrahydropterine (6-MPH4), 100 U catalase, and 1.0
      microM dithiothreitol in a total volume of 300 microl. The reaction was
      terminated by 1-ml suspension of activated charcoal in 0.1 M HCl. After
      centrifugation, 200-microl aliquots were mixed with 5 ml of cocktail for
      quantitation of [3H] H2O in supernatant. The results showed significant impact of
      pH rather than the buffer composition on the sensitivity of TH assay. An optimal
      pH range was found to be 5.5-6.0, whereas TH activity was significantly inhibited
      at pH 5.0 and pH 6.8 (F = 55.09, P = 0.000). A significantly high TH activity was
      observed with 1.5 mM 6-MPH4, whereas higher concentrations (3.0-4.5 mM) inhibited
      TH activity (F = 7.47, P = 0.005). Analysis of serially diluted striatal
      homogenates showed a significant correlation between TH activity and sample
      amount. The assay reaction was linear for 20- and 30-min incubation for rat and
      mice striata, respectively.

PMID- 15260123
TI  - Decreased copper-zinc superoxide dismutase activity and increased resistance to
      oxidative stress in glia maturation factor-null astrocytes.
AB  - Glia maturation factor (GMF) is a highly conserved protein found mainly in the
      nervous system. The current work was undertaken to investigate the effect of GMF
      expression in astrocytes on CuZn superoxide dismutase (CuZnSOD or SOD I) and on
      the vulnerability of the cells to H2O2 toxicity. Primary astrocyte cultures were
      derived from mice in which the GMF gene was completely deleted by homologous
      recombination (knockout). Astocytes derived from knockout animals displayed a
      lower level of CuZnSOD activity and protein. The reduction in CuZnSOD was
      restored by transfection with a GMF/adenovirus construct, and the resulting
      increase was blocked by the p38 MAP kinase inhibitor SB203580. There was no
      change in the other isoform of SOD (MnSOD or SOD II). Endogenous H2O2 was lower
      in the knockout cells, and the cells became more resistant to H2O2 toxicity
      compared to the wild type. In the GMF-null cells, concurrent with a decrease in
      CuZnSOD, the function of which is to convert superoxide to H2O2, there was an
      increase in the activity of the two enzymes that degrade H2O2: catalase and
      glutathione peroxidase. By regulating the redox state of the cell, GMF may be
      involved in a wide spectrum of cellular events ranging from survival,
      proliferation, differentiation, to death.

PMID- 15260124
TI  - Anti-narcoleptic agent modafinil and its sulfone: a novel facile synthesis and
      potential anti-epileptic activity.
AB  - We report a facile procedure to synthesize racemic modafinil
      (diphenylmethylsulfinylacetamide), which is now being used in pharmacotherapy,
      and its achiral oxidized derivative (diphenylmethylsulfonyl acetamide). Modafinil
      is of interest more than for its potential anti-narcoleptic activity. It has also
      been reported to have neuroprotective properties and may potentially be effective
      in the enhancement of vigilance and cognitive performance. Finally, it may also
      protect from subclinical seizures that have been implicated as causative factors
      in autistic spectrum disorders and other neurodegenerative conditions. This agent
      can now be synthesized simply and in larger amounts than previously, making it
      more readily available for testing in various research modalities. The described
      procedure also lends itself to production of several other amides of potential
      interest. We are currently in the process of synthesizing and testing several new
      derivatives in this series. The anticonvulsant properties of modafinil and its
      sulfone derivative have not previously been extensively described in the
      literature. It may be of interest to note that the oxidized derivative of
      modafinil is also nontoxic and almost as effective as an anticonvulsant as the
      parent.

PMID- 15260125
TI  - A 5-HT7 heteroreceptor-mediated inhibition of [3H]serotonin release in raphe
      nuclei slices of the rat: evidence for a serotonergic-glutamatergic interaction.
AB  - Midbrain slices containing the dorsal and medial raphe nuclei were prepared from
      rat brain, loaded with [3H]serotonin ([3H]5-HT), superfused, and the electrically
      induced efflux of radioactivity was determined. The nonselective 5-HT receptor
      agonist 5-carboxamido-tryptamine (5-CT; 0.001 to 1 microM) inhibited the
      electrically stimulated [3H]5-HT overflow from raphe nuclei slices (IC50 of 3.34
      +/- 0.37 nM). This effect of 5-CT on [3H]5-HT overflow was antagonized by the 5
      HT7 receptor antagonist SB-258719 (10 microM) and the 5-HT(1B/1D) antagonist SB
      216641 (1 microM), the IC50 values for 5-CT in the presence of SB-258719 and SB
      216641 were 94.23 +/- 4.84 and 47.81 +/- 4.66 nM. The apparent pA2 values for SB
      258719 and SB-216641 against 5-CT were 6.43 and 7.12, respectively. The
      inhibitory effect of 5-CT on [3H]5-HT overflow was weakly antagonized by 10
      microM of WAY-100635, a 5-HT1A receptor antagonist (IC50 6.65 +/- 0.56 nM,
      apparent pA2 4.99). The antagonist effect of SB-258719 (10 microM) on 5-CT-evoked
      [3H]5-HT overflow inhibition was also determined in the presence of 1 microM SB
      216641 or 1 microM SB-216641 and 10 microM WAY-100635, and additive interactions
      were found between the antagonists of 5-HT7 and 5-HT1 receptor subtypes. Addition
      of the Na+ channel blocker tetrodotoxin (1 microM) in the presence of SB-216641
      (1 microM) and WAY-100635 (10 microM) attenuated the inhibitory effect of 5-CT on
      KCl-induced [3H]5-HT overflow. These findings indicate that 5-CT inhibits [3H]5
      HT overflow from raphe nuclei slices of the rat by stimulation of 5-HT7 and 5
      HT(1B/1D receptors, whereas the role of 5-HT1A receptors in this inhibition is
      less pronounced. They also suggest that 5-HT7 receptors are probably not located
      on serotonergic neurons and thus may serve as heteroreceptors in regulation of 5
      HT release in the raphe nuclei. 5-CT (0.1 microM) also inhibited [3H]glutamate
      release, and SB-258719 (10 microLM) suspended this effect. We therefore
      speculated that the axon terminals of the glutamatergic cortico-raphe neurons may
      possess 5-HT7 receptors that inhibit glutamate release, which consequently leads
      to decreased activity of serotonergic neurons. The postulated glutamatergic
      serotonergic interaction in the raphe nuclei was further evidenced by the finding
      that N-methyl-D-aspartate and AMPA enhanced [3H]5-HT release.

PMID- 15260126
TI  - Dopamine receptors in the human dura mater.
AB  - Dopamine receptors (Dar) were studied as a component of the nervous dopaminergic
      system in the human dura mater. Dar were stained in several dural zones
      (vascular, perivascular, intervascular) in different regions (basal, calvarial,
      tentorial, occipital, frontal, parietal, temporal) of the cranial meninges.
      Specimens of human dura mater were harvested from autopsies of 10 elderly male
      subjects (age range, 60-75 years). Dar were labeled with specific (H3) markers,
      studied with radiobinding techniques (including liquid scintillation), stained
      for light microscope autoradiography, and measured by means of quantitative
      analysis of images. All results were evaluated with statistical analysis to
      identify significant results. More dural Dar were found in the basal region than
      in the calvarial one. Moreover, Dar are more abundant in the vascular and
      perivascular dural zone than in the intervascular one. The vascular distribution
      of Dar seemed to indicate that Dar play a role in the control of meningeal blood
      vessels. The location and distribution of D1 and D2 receptors in the human
      cranial dura mater confirmed the presence of a dopaminergic system, which could
      play an important role in controlling blood flow and/or other functions of
      meningeal membranes.

PMID- 15260127
TI  - Organochalcogens affect the glutamatergic neurotransmission in human platelets.
AB  - Blood platelets have repeatedly been suggested as an excellent model for various
      aspects of the synaptic apparatus. Considering that organochalcogens affect some
      parameters of glutamatergic neurotransmission in rats, in the current study we
      evaluated the effect of diphenyl diselenide (PhSe)2, diphenyl ditelluride
      (PhTe)2, and Ebselen on glutamatergic neurotransmission in human platelets.
      (PhTe)2 and (PhSe)2 caused a significant inhibition, but Ebselen did not
      interfere in Na-independent glutamate binding. Dithiothreitol (DTT) did not
      completely prevent the [3H]glutamate binding inhibition caused by 100 microM
      (PhTe)2. (PhSe)2, (PhTe)2, and Ebselen (100 microM) significantly inhibited
      [3H]glutamate uptake, whereas organochalcogens at 1 and 10 microM had no
      significant effect on the [3H]glutamate uptake in human platelets. In this study,
      platelets were demonstrated to be a suitable model for neurotoxicological
      research, and, to the best of our knowledge, this is the first report documenting
      the toxic effects of organochalcogens in human platelets.

PMID- 15260128
TI  - Metabotropic glutamate receptors modulate ischemia-induced GABA release in mouse
      hippocampal slices.
AB  - The involvement of glutamate receptors in GABA release in ischemia was
      investigated in hippocampal slices from adult (3-month-old) and developing (7-day
      old) mice. For in vitro ischemia, the slices were superfused in glucose-free
      media under nitrogen. Ionotropic glutamate receptor agonists failed to affect the
      ischemia-induced basal GABA release at either age. The K(+)-stimulated release in
      the immature hippocampus was potentiated by N-methyl-D-aspartate receptors,
      whereas in adults this release was reduced by both kainate and 2-amino-3-hydroxy
      5-methyl-4-isoxazoleproprionate receptor activation. The group I metabotropic
      receptor agonist (1+/-)-1-aminocyclopentane-trans-1,3-dicarboxylate enhanced the
      basal ischemic GABA release in a receptor-mediated manner in adults, this being
      concordant with the positive modulation of GABAergic neurotransmission by group I
      metabotropic glutamate receptors. (1 +/-)-1-Aminocyclopentane-trans-1,3
      dicarboxylate and (S)-3,5-dihydroxyphenylglycine also enhanced the K(+)
      stimulated release in the developing hippocampus in a receptor-mediated manner.
      Because group I receptors generally increase neuronal excitability, the enhanced
      GABA release may attenuate hyperexcitation or strengthen inhibition, being thus
      neuroprotective, particularly under ischemic conditions. Group III metabotropic
      glutamate receptors were not at all involved in ischemic GABA release in the
      immature mice, but in adults their activation by O-phospho-L-serine potentiated
      the basal release and reduced the K(+)-stimulated release. These opposite effects
      were abolished by the antagonist (RS)-2-cyclopropyl-4-phosphonophenylglycine.
      Metabotropic glutamate receptors, namely group I and III receptors, are able to
      modify the release of GABA from hippocampal slices under ischemic conditions,
      both positive and negative effects being discernible, depending on the age and
      type of receptor activated.

PMID- 15260129
TI  - Interstitial concentrations of amino acids in the rat striatum during global
      forebrain ischemia and potassium-evoked spreading depression.
AB  - The early detection and appropriate treatment of brain ischemia is of paramount
      importance. The interstitial concentrations of neurotransmitter amino acids are
      often used as an index of neuronal injury. However, monitoring of non
      neurotransmitter amino acids may be equally important. We have studied the
      behavior of 10 amino acids during K(+)-induced spreading depression (application
      of 70 mM KCl during 40 min) and global forebrain ischemia (two-vessel occlusion
      with hypotension during 20 min). The concentrations of glutamate, aspartate,
      taurine, GABA, glycine, and alanine, measured in the rat striatum by
      microdialysis, increased during both ischemia and spreading depression, whereas
      glutamine concentrations decreased in both cases. Only ischemia, but not
      spreading depression, led to enhanced release of serine, threonine, and
      asparagine. We thus conclude that an elevation in the interstitial concentrations
      of non-neurotransmitter amino acids is specific to deep ischemic injury to
      nervous tissue. We propose the monitoring of serine, asparagine, and threonine,
      together with excitatory amino acids, as an index of the degree of ischemic brain
      injury.

PMID- 15260130
TI  - Molecular basis of anti-apoptotic effect of immunophilin ligands on hydrogen
      peroxide-induced apoptosis in human glioma cells.
AB  - To clarify the molecular basis of the cytoprotective properties of immunophilin
      ligands (IPLs), the anti-apoptotic effects of IPLs were determined in human
      glioma U251 cells. GPI1046 and V10367, non-immunosuppressive IPLs (NI-IPLs), as
      well as FK506, an immunosuppressive IPL (I-IPL), had cytoprotective effects
      against hydrogen peroxide (H20O)-induced apoptotic cell death in U251 cells. H2O2
      increased both the ratio of bax/bcl-2 and the p53 mRNA expression. However, pre
      treatment with FK506 and V10367 significantly prevented any increase in this
      ratio or p53 mRNA expression. GPI1046 also reduced the ratio of bax/bcl-2 to the
      normal level. In addition, H2O2 significantly increased activities of all three
      caspases, caspase-3, caspase-8, and caspase-9, in comparison with non-H2O2
      controls. However, FK506 prevented the increase of these caspase activities. On
      the other hand, it is well-known that glutathione (GSH) and neurotrophic factor
      (NTF) is related to the induction of apoptosis in neuronal cells. In U251 cells,
      FK506, GPI1046 and V10367 had GSH-activating and NTF-activating effects. Thus,
      the immunosuppressive effect is not essential for the cytoprotective properties
      of IPLs, and IPLs have multiple beneficial properties such as the anti-apoptotic
      effect, GSH-activating effect, and NTF-activating effect, although the anti
      apoptotic effect of NI-IPLs is independent of the regulation of apoptotic
      activators such as caspase-3.

PMID- 15260132
TI  - Role of intracellular calcium stores on the effect of metabotropic glutamate
      receptors on phosphorylation of glial fibrillary acidic protein in hippocampal
      slices from immature rats.
AB  - Phosphorylation of glial fibrillary acidic protein (GFAP) in slices from immature
      rats is stimulated by glutamate via a group II metabotropic glutamate receptor
      (mGluR II) and by absence of external Ca2+ in reactions that are not additive
      (Wofchuk and Rodnight, Neurochem. Int. 24:517-523, 1994). These observations
      suggested that glutamate, via an mGluR, inhibits Ca(2+)-entry through L-type Ca2+
      channels and down-regulates a Ca(2+)-dependent dephosphorylation event coupled to
      GFAP. Because ryanodine receptors are present on internal Ca2+ stores and are
      associated with L-type Ca(2+)-channels, we investigated the possibility that the
      glutamatergic modulation of GFAP phosphorylation involves internal Ca2+ stores
      regulated by ryanodine receptors and whether the Ca2+ originating from these
      stores acts in a similar manner to external Ca2+. The results showed that the
      ryanodine receptor-agonists, caffeine and ryanodine and thapsigargin, all of
      which in appropriate doses increase cytoplasmic Ca2+, reversed the stimulation of
      GFAP phosphorylation given by 1S,3R-ACPD, an mGluR II agonist.

PMID- 15260131
TI  - Extraordinary changes in excitatory amino acid levels in cerebrospinal fluid of
      influenza-associated encephalopathy of children.
AB  - The correlation between the glutamate-glutamine cycle and nitric oxide (NO)
      production in the central nervous system (CNS) of a new type of influenza
      associated encephalopathy in children is discussed. When measurements of several
      amino acids and NOx (nitrite/nitrate) levels in the cerebrospinal fluid (CSF)
      using HPLC-fluorescence and -UV methods, respectively, were made. the CSF
      glutamate levels of patients with the new type of encephalitis were significantly
      lower, and both glutamine and NOx levels were significantly higher than those of
      the control group and the patients of the meningitis group. Results indicate that
      the turnover rate of glutamate in CNS, particularly in the brain, increases in
      the influenza-associated encephalopathy. The high mortality in the disease may
      correlate with the hyperactivity of supra-spinal glutamate neurons and the
      subsequent high activity levels of NOx in CNS.

PMID- 15260133
TI  - High extracellular K+ levels stimulate acetate oxidation in brain slices from
      well and malnourished rats.
AB  - We investigated the effect of high (12, 20, and 50 mM) extracellular K+
      concentrations ([K+]0) on [U-14C] acetate oxidation to CO2 in cerebral cortex
      slices of control and perinatal malnourished rats. High [K+]o increased the
      acetate oxidation, compared with a medium containing 2.7 mM [K+]0. By
      investigating the mechanisms involved in this stimulation, it was shown that (i)
      ouabain (1 mM) and monensin (10 microM) prevented this increase; (ii) in a medium
      with physiological [K+]0 (2.7 mM), the decreasing of [Na+]0 stimulated acetate
      oxidation. These results suggest that the stimulatory effect of [K+]0 on acetate
      oxidation was due to the decreasing of Na1 levels. Considering that malnutrition
      could alter the activity of Na+,K(+)-ATPase and/or other pertinent proteins, its
      effect on acetate oxidation was investigated. The malnutrition, which altered the
      body and cerebral weight of rats, did not modify the acetate oxidation in any
      protocol.

PMID- 15260134
TI  - Inhibition by anandamide and synthetic cannabimimetics of the release of [3H]D
      aspartate and [3H]GABA from synaptosomes isolated from the rat hippocampus.
AB  - Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization
      induced suppression of inhibition or excitation in hippocampus. This mechanism
      may underlie the impairment of some cognitive processes produced by these
      compounds, including short-term memory formation in the hippocampus. In this
      study, we investigated several compounds known to interact with CB receptors,
      evaluating their effects on K(+)-evoked release of [3H]D-aspartate ([3H]D-ASP)
      and [3H]GABA from superfused synaptosomes isolated from the rat hippocampus.
      [3H]D-ASP and [3H]GABA release were inhibited to different degrees by the
      synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2'
      chloroethylamide/N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), as
      well as by the endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2
      AG). Both types of release were also inhibited by capsaicin. The inhibition
      produced by each of the cannabinoid compounds and capsaicin was unaffected by
      capsazepine or by the CB1-receptor antagonists AM-251 and SR141716A. The
      mechanism underlying AEA- and synthetic CB-induced inhibition of the release of
      [3H]GABA and [3H]D-ASP from rat hippocampal synaptosomes might not involve
      activation of presynaptic CB1 receptors.

PMID- 15260135
TI  - The effect of citalopram on gene expression profile of Alzheimer lymphocytes.
AB  - Antidepressants are widely used in the treatment of mood disorders associated
      with dementia, however little information is available on their effect at the
      molecular level. In certain neurodegenerative disorders, such as in Alzheimer's
      disease, lymphocytes have been used to assess mirror changes that thought to
      occur in the brain. Gene expression profiles of lymphocytes from Alzheimer
      patients have been shown to differ from that seen with controls. To address this
      issue in light of antidepressant treatment, we used lymphocytes derived from
      Alzheimer's disease patients and control individuals to assess the impact of the
      selective serotonine reuptake inhibitor citalopram on gene expression using a
      cDNA microarray representing 3200 distinct human genes. Sequences that are
      differentially regulated after treatment with citalopram were identified and
      categorized based on similarities in biological functions. This analysis revealed
      that the overexpression of genes in control and Alzheimer white blood cells by
      citalopram are implicated in cell survival. Apart from this, citalopram did not
      markedly alter genes involved in other molecular functions in control cells. In
      contrast, alteration of genes implicated in ionic currents, cell-adhesion, immune
      mechanism, and adrenergic functions, were also observed in Alzheimer lymphocytes.
      The expression of genes of Alzheimer lymphocytes by citalopram is modulated
      differently which may correlate with the pathology.

PMID- 15260136
TI  - NF-kappaB prevents TNF-alpha-induced apoptosis in an oligodendrocyte cell line.
AB  - Nuclear factor kappa beta (NF-kappaB) inhibits apoptosis in sensory, hippocampal,
      and striatal neurons of the central nervous system. Although several apoptotic
      stimuli have been shown to activate NF-kappaB in oligodendrocytes, the function
      of NF-kappaB in this cell type remains unknown. In this study, we introduced
      plasmids expressing either the p50- or p65-subunit of human NF-kappaB into
      Central Glia-4 (CG-4)--a rat oligodendrocyte precursor cell line-and determined
      the influence of NF-kappaB function on tumor necrosis factor-alpha (TNF-alpha)
      induced apoptosis. Expression of NF-kappaB markedly prevented CG-4 apoptosis,
      with p50 being more effective than p65. This anti-apoptotic activity was
      repressed by IkappaB-alpha, an inhibitor of NF-kappaB. These results imply that
      NF-kappaB acts as a potent inhibitor of TNF-induced apoptosis in
      oligodendrocytes.

PMID- 15260138
TI  - Sequential memory: a developmental perspective on its relation to frontal lobe
      functioning.
AB  - The multidimensional nature of the frontal lobes serves to organize and
      coordinate brain functionings playing a central and pervasive role in human
      cognition. The executive processes implicated in complex cognition such as novel
      problem solving, modifying behavior as appropriate in response to changes in the
      environment, inhibiting prepotent or previous responses, and the implementation
      of schemas that organize behavior over time are believed to be mediated by the
      frontal regions of the brain. Overall, the functioning of the frontal lobes
      assists individuals in goal directed and self-regulatory behavior. Additional
      theories of frontal lobe functioning have focused on its involvement in temporal,
      or time-related domains. The organizational and strategic nature of frontal lobe
      functioning affects memory processes by enhancing the organization of to-be
      remembered information. Among the specific memory systems presumed to be based on
      anterior cerebral structures is the temporal organization of memory. An essential
      component of memory that involves temporal organization is sequential ordering
      entailing the ability to judge which stimuli were seen most recently and the
      temporal ordering of events in memory. Focal lesion studies have demonstrated the
      importance of the frontal lobes on retrieval tasks in which monitoring,
      verification, and placement of information in temporal and spatial contexts of
      critical importance. Similarly, frontal lobe damage has been associated with
      deficits in memory for the temporal ordering, or sequencing, of events. The
      acquisition of abilities thought to be mediated by the frontal lobes, including
      sequential memory, unfolds throughout childhood, serving to condition patterns of
      behavior for the rest of the brain. Development of the frontal regions of the
      brain is known to continue through late adolescence and into early adulthood, in
      contrast to the earlier maturation of other cortical regions. The developmental
      patterns of the frontal lobes are thought to involve a hierarchical, dynamic, and
      multistage process.

PMID- 15260139
TI  - A critical review of the clinical effects of therapeutic irradiation damage to
      the brain: the roots of controversy.
AB  - We critically examined the damaging affects of therapeutic irradiation by
      comparing results from cross-disciplinary studies of early- and late-delayed
      radiotherapy effects. Focus is attained by concentrating on clinical treatment
      issues (volume of brain, dose, timing of effects, age, modality types, and
      stereotactic treatment techniques), rather than on methodological means or
      problems, which is necessary to understand the mechanisms and characteristics of
      radiotherapy-induced behavioral dysfunction including cognition. We make
      observations and hypotheses about the actual risks from radiotherapy that could
      be informative in the treatment decision process, and which may lessen the
      concerns of some patients and their families about the risks they take when
      receiving radiation. Conditions that predispose to radiation injury are reviewed:
      (1) higher doses even to part of the brain versus lower doses to the whole brain,
      (2) combined treatment modalities, (3) malignancy itself, (4) radiation early
      during postnatal brain development, and (5) late-delayed effects (more than 3
      years posttreatment). Current neurocognitive frameworks for understanding
      cognitive change over time in children and adults are summarized, along with the
      literature on effects of brain tumors and treatment on depression. No studies
      have as yet identified candidate brain regions that are more sensitive to
      radiotherapy. Two studies have provided early, preliminary evidence for a
      specific vulnerability of visual attention/memory to the early stage of late
      radiation damage. Furthermore, radiation effects appear severe only in a minority
      of patients. Risk is related to direct and indirect effects of cancer type,
      concurrent clinical factors, and premorbid risk factors.

PMID- 15260140
TI  - Molecular phylogeny of the genus Paramesotriton (Caudata: Salamandridae).
AB  - To elucidate the phylogeny of the genus Paramesotriton (Caudata: Salamandridae),
      we investigated three mitochondrial DNA gene fragments (1207 bp in total) of
      cytochrome b, ND2, and ND4 for its six recognized species. The phylogenetic
      relationships within Paramesotriton were reconstructed by maximum parsimony (MP)
      and maximum likelihood (ML) methods. Phylogenetic trees (MP and ML trees) that
      were constructed from the combined data set of the three gene fragments indicated
      that all six species of Paramesotriton formed a monophyletic group, with P.
      caudopunctatus as basal to the other five species. This result suggests that P.
      fuzhongensis is a valid species in Paramesotriton.

PMID- 15260141
TI  - Species-specific allozyme markers for Appalachian wood-feeding cockroaches
      (Dictyoptera: Cryptocercidae).
AB  - Members of the genus Cryptocercus are wood-feeding cockroaches that live in the
      temperate forests. Nine species are recognized in the genus worldwide: two in
      eastern Eurasia, two in China, and five in the United States. Within the United
      States, one species occurs in the Pacific Northwest and four occur in the
      Appalachian Mountains. Previous studies have revealed the presence of potential
      zones of overlap in distribution among the Appalachian species, raising the
      possibility of hybridization among them. Differences in mitochondrial DNA have
      previously been identified for the Appalachian species. However, to identify
      hybrid individuals one or more species-specific, codominant nuclear markers are
      required. Therefore, our objective was to undertake allozyme analysis of
      enzymatic loci to identify fixed, species-specific alleles for the four
      Appalachian species. We assayed a mean of 42 individuals each from 16 sites for
      allozyme variation for the four species. At 6 of the 33 loci examined, fixed
      alternate alleles were identified; a combination of 2 loci enabled the
      identification of all four species. To identify hybrids in the field, we examined
      42 individuals each from 13 sites in which two or more of the above species occur
      in close proximity for presence of heterozygous individuals at one or more of the
      six fixed loci. No heterozygous individuals were found suggesting the lack of
      hybridization among the Appalachian species.

PMID- 15260137
TI  - Clinical implications and methodological challenges in the study of the
      neuropsychological correlates of cannabis, stimulant, and opioid abuse.
AB  - Chronic consumption of several drugs of abuse (cannabis, stimulants, opioids) has
      been associated with the presence of neuropsychological impairments in a broad
      range of functions. Nevertheless, in recent years neuropsychological research on
      substance abuse has focused on the study of impairments in the executive
      functions linked to the prefrontal cortex and their influence on the personality,
      cognitions, and behaviors of the substance abusers. The aim of our review is,
      first, to summarize the main neuropsychological impairments shown by classic
      studies, as well as these new discoveries in executive functioning; second, to
      consider the mediating role of neuropsychological status on treatment outcomes
      and analyze the impact of these impairments in clinical practice with drug
      addicts; and third, to review the principal methodological challenges associated
      with research in the field of the neuropsychology of substance abuse. We also
      highlight the convenience of intervening in those functions most relevant to the
      abusers' persistence in consumption and risk of relapse.

PMID- 15260142
TI  - Identification of amylase inhibitor deficient mutants in pigeonpea (Cajanus cajan
      (L.) Millisp.).
AB  - We have developed and analyzed several mutant lines (M6 generation) of pigeonpea
      (Cajanus cajan (L.) Millsp.) for the content of defensive proteins and
      antinutritional factors. Inhibitors of proteinase and of amylase, lectins, and
      raffinose family oligosaccharides were analyzed in mature seeds of different
      pigeonpea accessions (untreated) and compared with mutant lines. Proteinase
      inhibitor profiles were similar in terms of number and intensities of activity
      bands but they differ marginally in the activity units in pigeonpea accessions
      and mutants. Pigeonpea mutants showed significant differences in amylase
      inhibitor profiles as well as activity units from those of pigeonpea accessions.
      Interestingly, two mutants (A6-5-1 and A7-3-2) were identified to have absence of
      amylase inhibitor isoforms. Hemagglutinating activity and raffinose family
      oligosaccharides content were found to be significantly higher in mutants than in
      accessions. It is evident from the results that proteinase inhibitors of
      pigeonpea are stable while amylase inhibitors, lectins, and raffinose family
      oligosaccharides show altered expression upon mutagen treatments. These mutants
      will be ideal candidates for further evaluation.

PMID- 15260143
TI  - Polymorphisms in blood proteins of Bos indicus and Bos taurus cattle breeds of
      Cameroon and Nigeria, and description of new albumin variants.
AB  - Polymorphisms in the five blood protein loci albumin (ALB), carbonic anhydrase
      (CA II), vitamin D binding protein (GC), haemoglobin (HBB), and transferrin (TF)
      were investigated in 520 individuals from 12 cattle populations (Bos indicus and
      Bos taurus) in Cameroon and Nigeria by isoelectric focusing with carrier
      ampholytes in ultrathin polyacrylamide gels (PAG-IEF) and by linear gradient
      polyacrylamide gel electrophoresis (PAGE). While all loci in nine populations
      were polymorphic with up to six alleles at the ALB and TF loci: the Namchi
      population showed monomorphism at the CA II locus and Muturu at the ALB, CA II,
      and HBB loci. There was a clear distinction between Bos indicus and Bos taurus
      breeds at the ALB locus with ALBB predominating in indicine and ALBA
      predominating in taurtine breeds. CA IIS, GCA, and HBBA were the most commonly
      occurring alleles in all populations. Two variants not described before were
      demonstrated by PAG-IEF at the ALB locus and named ALBJ and ALBK. Mean effective
      number of alleles as measure of intrabreed diversity was higher in zebu
      populations (2.040-2.288) as compared to taurine breeds (1.349-1.836).
      Significant deviations from Hardy-Weinberg equilibrium occurred in some
      populations at the HBB and TF loci. More haplotypes of ALB/GC occurred in the
      zebu than taurine breeds. ALBAGCA predominated in the taurine populations and
      ALBBGCA in the indicine populations. Influence of zebu genes on the Namchi and
      N'Dama taurine breeds was detected at the ALB, CA II, HBB, and TF loci, and
      estimated at 61.5% and 5.7%, respectively. The high resolution of PAG-IEF in
      screening for polymorphisms within diversity studies was demonstrated.

PMID- 15260144
TI  - Distinct genes produce the alcohol dehydrogenases of pollen and maternal tissues
      in Petunia hybrida.
AB  - Analysis of cDNA clones derived from hypoxic root mRNA of Petunia hybrida has
      revealed the existence of a third active gene encoding alcohol dehydrogenase in
      petunia. A combination of RT-PCR and ADH activity gels provide evidence for the
      selective tissue-specific expression of these three genes in multiple floral
      organs and hypoxically stressed roots. Expression of adh 1 in the plant appears
      to be restricted to immature pollen grains; the other two genes are expressed
      differentially in maternal anther tissues, stigma, petals, and hypoxic root. This
      work underscores the utility of RT-PCR for distinguishing expression patterns of
      closely related genes, clarifies the expression patterns exhibited by members of
      this gene family, and suggests multiple functions for the adh genes of petunia.

PMID- 15260145
TI  - A PCR-based analysis of Hox genes in an earthworm, Eisenia andrei (Annelida:
      Oligochaeta).

PMID- 15260146
TI  - Systematics of tropical eastern Pacific fishes.

PMID- 15260147
TI  - Gymnothorax eurygnathos, a new moray from the Gulf of California (Anguilliformes:
      Muraenidae).
AB  - A new species of moray eel from deep water in the Gulf of California is
      described. It is dark brownish-black with an overall pattern of pale irregular
      blotches; a short, broad head; wide, triangular jaws; deeply serrate and
      partially biserial teeth; dorsal-fin origin above and behind gill opening; and 10
      predorsal, 66 preanal, and 134 total vertebrae. This combination of characters is
      not shared by any other moray species.

PMID- 15260148
TI  - Gordiichthys combibus, a new species of eastern Pacific sand-eel (Anguilliformes:
      Ophichthidae).
AB  - A new species of bascanichthyin ophichthid, Gordiichthys combibus, is described
      from shallow water along the Pacific coast of Colombia. It is the first known
      eastern Pacific species of Gordiichthys and is very similar to G. randalli from
      Puerto Rico. It differs from its other western Atlantic congeners in vertebral
      number and other characters. A key to the genus is provided.

PMID- 15260149
TI  - Aplatophis zorro, a new species of eastern Pacific snake-eel, with comments on
      New World ophichthid distributions (Anguilliformes: Ophichthidae).
AB  - Aplatophis zorro n. sp., the first known eastern Pacific species of this New
      World genus, is described from a shallow water trawl-caught specimen from the
      Golfo de San Miguel, Pacific Panama. It is similar to its only known congener, A.
      chauliodus from the tropical western Atlantic, but differs in its vertebral
      number, dentition, coloration, and other characters. Comments concerning the
      distribution of New World ophichthids are provided.

PMID- 15260150
TI  - Notes on Galapagos grenadiers (Pisces, Gadiformes, Macrouridae), with the
      description of a new species of Coryphaenoides.
AB  - Two unusual specimens of the grenadier genus Coryphaenoides were collected by the
      deep-submersible vehicle Johnson Sea-Link off the Galapagos. Unlike any other
      member of the genus, the snout in these specimens was rounded, non-protruding,
      naked anteriorly and ventrally, with no tubercular scales marking the terminal
      and lateral angles. They are herein described as Coryphaenoides gypsochilus.
      Additional specimens of grenadiers were procured by the Johnson Sea-Link,
      including the second and third specimens of Nezumia ventralis and the first
      record of Caelorinchus canus from these waters. Three species and one subspecies
      of Galapagos grenadiers are endemic.

PMID- 15260151
TI  - A new species of Nezumia (Gadiformes: Macrouridae) from Fieberling Guyot, eastern
      North Pacific Ocean.
AB  - A new species of the macrourine genus Nezumia is described from specimens
      collected from the crest of Fieberling Guyot in the eastern North Pacific Ocean.
      The new species is distinguishable from all other Nezumia species chiefly on the
      basis of a high number of pelvic fin rays, a relatively high number of first
      dorsal fin soft rays, a steep blunt snout lacking scales ventrally, a relatively
      weak suborbital ridge, and a moderately long, thin barbel. Although possibly
      endemic to the Baja California Seamount Province, the new species appears to lack
      close relatives among the other Nezumia species of the eastern North Pacific
      Ocean. It might have arrived there either from a disjunct Tethyan distribution,
      thus retaining close relatives among the Atlantic Ocean species of Nezumia, or by
      way of stepping-stone dispersal from the Indo-west Pacific Ocean.

PMID- 15260152
TI  - A new species of halfbeak, Hyporhamphus naos (Beloniformes: Hemiramphidae), from
      the tropical eastern Pacific.
AB  - The tropical eastern Pacific halfbeak previously considered conspecific with the
      western Atlantic Hyporhamphus unifasciatus (Ranzani 1842) is described as a new
      species, H. naos. It resembles H. meeki from the Atlantic and Gulf coasts of the
      United States in number of gill rakers on the first arch (usually 32-36, mean
      33.6), more than in H. unifasciatus (usually 29-32, mean 30.6), but fewer than in
      other sympatric species of eastern Pacific Hyporhamphus. Results of a three
      treatment ANCOVA (H. naos, H. meeki, and H. unifasciatus) show significant
      differences in slopes and means for all 14 morphometric characters examined, 9 of
      14 characters comparing H. naos with H. unifasciatus, and 7 of 14 comparing H.
      naos with H. meeki. Protein electrophoretic patterns clearly distinguish all
      three species with a number of fixed allelic differences.

PMID- 15260153
TI  - Status of the eastern Pacific agujon needlefish Tylosurus pacificus
      (Steindachner, 1876) (Beloniformes: Belonidae).
AB  - Tylosurus pacificus (Steindachner, 1876) is confirmed to have full species rank
      based on: 1) sympatry with T. acus melanotus at Isla Gorgona and in Panama; 2)
      level of morphological differentiation in numbers of vertebrae, dorsal and anal
      fin rays; and 3) level of mtDNA differentiation. The eastern Pacific agujon
      needlefish is found from the Gulf of California, Mexico, to Peru, including the
      Galapagos Islands.

PMID- 15260154
TI  - Description of a new weakfish, Cynoscion nortoni, from Ecuador with a note on the
      distribution of Umbrina bussingi (Perciformes: Sciaenidae).
AB  - A new sciaenid was found at a fish market on the Ecuadorian coast. Cynoscion
      nortoni, described from 11 specimens, is characterised by a relatively large eye,
      a long head and pectoral fin, a high dorsal fin-ray count and a dark, steel grey
      colour on its dorsum. The specimens were captured over the continental shelf with
      a long line at depths between 100 and 200 meters. Another deep water species,
      Umbrina bussingi, is recorded for the first time from southern Colombia.

PMID- 15260155
TI  - Two new species of Stellifer from inshore waters of the eastern Pacific, with a
      redescription of S. ephelis (Perciformes: Sciaenidae).
AB  - Two new species of Stellifer from the eastern Pacific coast are described.
      Stellifer walkeri n. sp. and S. wintersteenorum n. sp. are both found in coastal
      waters off southern Mexico. They are distinguished from other species of
      Stellifer by having two sharp spines at the lower margin of the preopercle and
      four sensory pores at the tip of the lower jaw. Stellifer wintersteenorum can be
      distinguished from S. walkeri by having jet black pigment on the roof of the
      mouth and pharyngeal cavity. Stellifer wintersteenorum can be further
      distinguished from S. furthii (Steindachner), which also has a black mouth
      lining, by having a pair of short diverticula on the anterior chamber of the gas
      bladder compared with those of S. furthii, which are extended posteriorly as
      long, narrow tubes. Stellifer walkeri is further distinguished from S.
      pizarroensis Hildebrand by having fewer gill rakers (36-38 vs. 51-55) and soft
      anal-fin rays (9 vs. 10-11), and from S. zestocarus Gilbert by having two,
      instead of one preopercular spines, more gill rakers (36-38 vs. 29-32) and a
      smaller eye (4.5-4.8 vs. 3.6-4.2 in head length). Stellifer ephelis Chirichigno,
      which was incompletely described when named, is redescribed based on materials
      from throughout the species' range. A key to the eastern Pacific species of
      Stellifer is also included.

PMID- 15260156
TI  - A new genus and new species of Sciaenidae from the Gulf of Panama (Perciformes:
      Sciaenidae).
AB  - Paranebris bauchotae, a new genus and species of sciaenid from the Gulf of Panama
      is described from three specimens (138-212 mm SL). It is distinguished from all
      other sciaenids by having granulated tooth plates on the jaws and the
      premaxillary tooth plates that are exposed laterally of the lower jaw when the
      mouth is closed. The new genus shares the following characters with the New World
      genus Nebris: a thick fleshy and cartilage gap present between premaxillary bones
      where the ascending processes form an A-frame arch; gas bladder with a pair of
      long U-shaped appendages; and a thick, oval-shaped sagitta with deeply grooved
      caudal section of the sulcus. Paranebris bauchotae is distinct from all Nebris
      species in having a firmer interorbital skin and scale cover (spongy to the touch
      in Nebris), a larger eye (6-7 vs. 8-12 times in head length) and large ctenoid
      scales (vs. small and cycloid in Nebris).

PMID- 15260157
TI  - Wrasses of the Galapagos Islands, with the description of a new deepwater species
      of Halichoeres (Perciformes: Labridae).
AB  - Halichoeres raisneri, new species, is described from three specimens captured by
      the Johnson Sea Link submersible at 114-125 m off Wolf Island, Galapagos.
      Distinctive features of the new species include a dorsally projecting fleshy flap
      along the posterior three-quarters of the upper lip and the absence of a canine
      tooth at the corner of the upper jaw. The body color of freshly caught females is
      pale pink with two yellow stripes and five prominent pink spots above the
      uppermost stripe. Similarities between the new species and other labrids are
      discussed, and a key to the 16 nominal species of Labridae known from the
      Galapagos Islands is provided. Decodon melasma is recorded from the Archipelago
      for the first time.

PMID- 15260158
TI  - A review of the razorfishes (Perciformes: Labridae) of the eastern Pacific Ocean.
AB  - Several new species of the razorfish genus Xyrichtys have been discovered
      recently in the tropical eastern Pacific region. The taxonomy of this group of
      fishes is not clear, since juveniles, females, and males often have different
      color patterns and morphologies, and some species descriptions are incomplete. We
      review the members of this genus in this region based on our recent collections
      and describe the juvenile, initial, and terminal phase color patterns of the Cape
      razorfish, Xyrichtys mundiceps. We question the validity of Xyrichtys perlas,
      which appears to represent the initial phase of X. mundiceps. We conclude that
      six species of Xyrichtys are present in the tropical eastern Pacific, including
      one undescribed species we have collected from the Galapagos Islands and one
      uncollected new species from the Revillagigedos Islands. Xyrichtys mundiceps is
      found in Baja California and in Panama Xyrichtys pavo is a large species found
      throughout the Indo-Pacific and eastern Pacific. Xyrichtys victori is a colorful
      species native to the Galapagos and Cocos Islands, and Xyrichtys wellingtoni is
      apparently endemic to Clipperton Atoll. The undescribed species is known only
      from the Galapagos Islands and has a dark-colored juvenile with extended first
      dorsal fin rays that are not separated from the remainder of the fin. The
      terminal phase of this species is unknown. We present keys to the known juvenile
      and initial phase stages of five species. In addition, we document the allometric
      growth of the head of razorfishes and show that the head shape of small
      individuals of Xyrichtys razorfishes is no different from that of the razorfish
      genus Novaculichthys, and therefore we suggest caution in using this character to
      distinguish these genera.

PMID- 15260159
TI  - Redescription of Ammodytoides gilli, the tropical eastern Pacific sand lance
      (Perciformes: Ammodytidae).
AB  - Ammodytoides gilli (Bean, 1895) is the correct name for the tropical eastern
      Pacific sand lance. Its range is extended from Cabo San Lucas, Baja California
      south to Panama, Ecuador, and the Galapagos Islands. Ammodytes lucasanus Beebe
      and Tee-Van, 1938 is a junior synonym. Types of both nominal species were re
      examined. The species is redescribed based on 50 specimens (42.3-115 mm SL) from
      12 lots and is compared with other known species of Ammodytoides. Changes in
      ontogeny from the smallest known specimen (42.3 mm SL, illustrated) are detailed
      including reduction in the posterior dorsal fin lobe and development of branched
      dorsal and anal fin rays.

PMID- 15260160
TI  - Review of the South American-Antarctic triplefin fish genus Helcogrammoides
      (Perciformes: Tripterygiidae).
AB  - The genus Helcogrammoides comprises three species of small, cryptic shorefishes,
      H. antarcticus, H. chilensis, and H. cunninghami. All three species inhabit
      shallow water along exposed rocky coasts. Specimens reported herein extend the
      known distributions of H. chilensis and H. cunninghami to the vicinity of Lima,
      Peru, approximately 1600 km north of their previously reported northernmost
      records in Chile. Helcogrammoides chilensis and H. cunninghami occur
      sympatrically over most of their ranges in Peru and Chile and are frequently
      taken together in the same field collections. Lectotypes are designated for H.
      chilensis and H. cunninghami. Diagnoses and an identification key are provided
      for the species.

PMID- 15260161
TI  - Protemblemaria perla, a new species of tube blenny (Perciformes: Chaenopsidae)
      from the tropical eastern Pacific.
AB  - Protemblemaria perla, from Isla del Rey, Islas Perlas, Panama, is distinctive in
      having a long unbranched cirrus on the posterior nostril, a U-shaped fleshy ridge
      bearing fleshy flaps and a pair of papillae on the nape, a relatively high number
      (18) of segmented dorsal-fin rays, and small rust-colored spots on the dorsal
      fin. Protemblemaria perla and P. punctata, from the southern Caribbean, share
      several morphological features and form a transisthmian species pair. Although
      the degree of color variation is unknown in P. perla, color varies greatly in P.
      bicirris and P. punctata, both of which have an orange morph.

PMID- 15260163
TI  - The eastern Pacific species of Bathygobius (Perciformes: Gobiidae).
AB  - The circumtropical gobiid genus Bathygobius Bleeker is defined and three Eastern
      Pacific species are redescribed, with first dorsal fin pattern and postorbital
      blotches being shown to be additional characters of diagnostic value. Two
      mainland species are recognised, the Mexican-Panamanian B. ramosus Ginsburg 1947
      and the Panamanian B. andrei (Sauvage 1880). B. ramosus is now reported from
      Clarion Island, Revillagigedos, and also from Cocos Island. Meristic variation of
      ramosus is tabulated for local populations and PCA analysis of their morphometry
      suggests regional differentiation in this species, with Tres Marias and
      Revillagigedos populations clustering away from mainland and Montuosa material.
      An insular species, B. lineatus (Jenyns 1842) from the Galapagos is defined, with
      B. arundelii (Garman 1899) from Clipperton Island and B. l. lupinus Ginsburg 1947
      from Lobos de Afuera, off Peru, placed as nominal subspecies of lineatus. This
      species resembles the Indo-west Pacific B. fuscus and Atlantic basin B. soporator
      more closely than it does ramosus and andrei and may be the product of
      transpacific dispersal. A similar origin for B. ramosus is discussed but it seems
      more likely that both B. ramosus and B. andrei have Caribbean sister species.

PMID- 15260162
TI  - Ptereleotris carinata, a new species of hovering goby (Perciformes:
      Microdesmidae) from the tropical eastern Pacific.
AB  - A new hovering goby or dartfish is described from material collected in Mexico,
      Costa Rica and Panama. It is the only species of the cosmopolitan genus
      Ptereleotris known from the eastern Pacific. It is distinguished from its Western
      Atlantic and Indo-Pacific congeners by its low fin-ray counts, prominent median
      keel on the ventral margin of the head, lanceolate caudal fin with dusky lower
      half and dusky blue or lavender body in adults.

PMID- 15260164
TI  - A preliminary review of the eastern Pacific species of Elacatinus (Perciformes:
      Gobiidae).
AB  - Elacatinus limbaughi is described as new from the Gulf of California. Elacatimus
      digueti is redescribed and Elacatinus inornatus Bussing is synonymyzed with E.
      digueti. Data are presented on geographical variation in Elacatinus puncticulatus
      and E. digueti. Species of the genus Elacatimus are normally associated with
      coral reefs and several of the species clean parasites from other fishes.
      Elacatinus is regarded as distinct from Gobiosoma, based on vertebral and other
      characteristics.

PMID- 15260165
TI  - Revision of the eastern Pacific species of Gobulus (Perciformes: Gobiidae), with
      description of a new species.
AB  - Gobulus birdsongi is described as a new species from the Pacific coast of Panama.
      The two other known species of Gobulus from the eastern Pacific, Gobulus
      crescentalis and G. hancocki are redescribed. Gobulus birdsongi differs from
      other species in the genus in having more numerous second dorsal and anal rays.
      Gobulus hancocki differs from G. crescentalis in having a much smaller eye. The
      genus is distinctive in having reversed countershading, with the ventral surface
      of the body darker than the dorsal surface.

PMID- 15260166
TI  - A new species of Trinectes (Pleuronectiformes: Achiridae), with comments on the
      other eastern Pacific species of the genus.
AB  - A new eastern Pacific achirid, Trinectes xanthurus, has a distinctive yellow or
      light caudal fin, without pattern, to contrast with its relatively dark body.
      This species also has black, posterior margins of the dorsal and anal fins and 21
      22 caudal vertebrae, versus 19-20 for its Pacific coast congeners. It usually is
      found in shallow, continental shelf waters on sand or mud bottoms and ranges from
      Colombia to El Salvador. The genus Trinectes is represented in the eastern
      Pacific by four species. A fifth species usually occurs in Pacific slope
      drainages (freshwater) in Panama. Of these species, only Trinectes fonsecensis is
      found throughout the tropical eastern Pacific, while the other three coastal
      species are confined to tropical waters south of the Golfo de Tehauntepec.

PMID- 15260167
TI  - Redescription of Symphurus diabolicus, a poorly-known, deep-sea tonguefish
      (Pleuronectiformes: Cynoglossidae) from the Galapagos Archipelago.
AB  - Symphurus diabolicus, previously known only from the holotype collected in 501 m
      west of Isla San Cristobal (Chatham Island), Galapagos Archipelago, is re
      described based on the holotype (112.6 mm SL) and 19 additional specimens (61.1
      123.5 mm SL) recently collected from deep waters around the Galapagos
      Archipelago. Symphurus diabolicus is characterized by: an elongate body; narrow
      head with pointed snout; 1-3-2 ID pattern; 106-110 dorsal-fin rays; 89-96 anal
      fin rays; 12 caudal-fin rays; 57-59 total vertebrae; 5 hypurals; extremely small
      scales; no pupillary operculum; large, prominent eyes, with migrated eye near
      dorsal margin of head; relatively short postorbital head length; relatively long
      snout and predorsal lengths; black peritoneum visible through abdominal wall on
      both sides of body; uniform olive green to dark brown ocular-side coloration with
      series of prominent, darker brown, elliptical to rectangular, blotches (not
      usually forming crossbands) along body at bases of dorsal and anal fins; and
      uniformly whitish or light yellow blind side. Symphurus diabolicus appears to be
      endemic to the Galapagos Archipelago, and is relatively common (captured at 16
      different localities) at depths of 308 to 757 m (observed as shallow as 245 m) in
      this region. Examination of this expanded series of specimens confirms the
      validity of S. diabolicus and provides characters to distinguish it from S.
      microlepis Garman, a similar species known only from the holotype taken at
      approximately 530 m off Pacific Panama.

PMID- 15260168
TI  - Introduction to Physidae (Gastropoda: Hygrophila); biogeography, classification,
      morphology.
AB  - Physidae, a world-wide family of freshwater snails with about 80 species, are
      reclassified by progressive characters of the penial complex (the terminal male
      reproductive system): form and composition of penial sheath and preputium,
      proportions and structure of penis, presence or absence of penial stylet, site of
      pore of penial canal, and number and insertions of penial retractor muscles.
      Observation of these characters, many not recognized previously, has been
      possible only by the technique used in anesthetizing, fixing, and preserving.
      These progressive characters are the principal basis of 23 genera, four grades
      and four clades within the family. The two established subfamilies are divided
      into seven new tribes including 11 new genera, with diagnoses and lists of
      species referred to each. Proposed as new are: in Aplexinae, Austrinautini, with
      Austrinauta g.n. and Caribnautu harryi g.n., nom.nov.; Aplexini; Amecanautini
      with Amecanauta jaliscoensis g.n., sp.n., Mexinauta g.n., and Mayabina g.n., with
      M. petenensis, polita, sanctijohannis, tempisquensis spp.nn., Tropinauta
      sinusdulcensis g.n., sp.n.; and Stenophysini, with Stenophysa spathidophallus
      sp.n.; in Physinae, Haitiini, with Haitia moreleti sp.n.; Physini, with
      Laurentiphysa chippevarum g.n., sp.n., Physa mirollii nom.nou.; and Physellini,
      with Chiapaphysa g.n., and C. grijalvae, C. pacifica spp.nn., Utahphysa g.n.,
      Archiphysa g.n., with A. ashmuni, A. sonomae spp.nn., Physella hemphilli sp.n.,
      and Ultraphysella sinaloae g.n., sp.n. The simplest reproductive system is found
      in Austrinauta of the Aplexinae; its penial complex approaches that in the
      related family Lymnaeidae. Within Physinae a close approximation is found in
      Haitia. By these two genera the two subfamilies are drawn close together. Four
      grades of progressive complexity are recognized: (I) penial sheath entirely
      muscular; (II) penial sheath with both glandular and muscular tissue; (III) penis
      with penial stylet or other specialization of the tip of the penis; and (IV) pore
      of penial canal lateral rather than terminal as in the lower grades. In both
      subfamilies there are clades with glandular tissue in the penial sheath, a penial
      sheath subdivided into two parts, and tip of penis specialized in various ways.
      These clades are formalized as new tribes. Of 23 genera of Physidae, 17 occur in
      Pacific drainages of North and Central America, eight of these restricted to the
      region. Concentration of primitive genera along the Pacific coast from Mexico to
      Costa Rica conforms to previous observations that primitive pulmonate families
      are concentrated within, or along the continental margins of, the Pacific Ocean.
      An ancestral origin of Physidae along an ancient eastern Pacific coast is
      probable. From this region the several lineages have spread north, south and east
      in the Americas, and through Siberia to Europe. Although Physinae have fewer
      genera than Aplexinae (11 v. 12), they have more species (47 v. 34). Greater land
      area in the temperate zone has provided more opportunity for speciation of
      Physinae, in contrast to the generally tropical and warm-temperate range of
      Aplexinae. Furthermore, 10 species of Physinae are localized in individual lakes,
      whereas Aplexinae are not lake-dwellers. Both well-developed egg strings and
      capsular strings are found in the spawn of Sibirenauta elongatus. These
      structures have been known in Lymnaeidae, but not hitherto in Physidae; they are
      a link with some marine groups, such as Siphonariidae. Spiral color bands and
      white streaks in the shell of Mexinauta recall those in Lancidae (Lymnaeacea),
      whereas the radula of Physidae is like that of Chilinidae. Physidae thus show
      affinities to various basal stocks of aquatic pulmonates; no clear-cut sister
      group can be recognized. Most species have a restricted range; out of 55 with
      sufficiently detailed information for analysis, 25 are limited to a single 1
      degrees x 1 degrees quadrangle. Only a few species are widespread, on one or even
      two continents. Accordingly, more species of Physidae are threatened by habitat
      destruction than in other families of Hygrophila with generally wider
      distributions. Other features are a key to genera; catalog of more than 430 names
      applied to living Physidae, with original reference, type locality, and location
      of type specimens; summary of museums with types; and glossary.

PMID- 15260169
TI  - A guide to the winged aphids (Homoptera) of Costa Rica.
AB  - This guide is a compilation of limited morphological and biological information
      on the winged morphs of 60 species of aphids that have been collected in Costa
      Rica. It should not be viewed as a definitive taxonomic treatise on the aphids of
      Costa Rica, rather it is a tool that can be used to assist in research on the
      biology, host plant relationships, taxonomy, and virus transmission capabilities
      of aphids. Each species is covered in an identical manner. Morphological and
      biological information is provided in both Spanish and English as well as
      photographs of slide mounted specimens. Keys are provided to help the user in
      identifying the species. Most of the specimens examined were taken in traps
      associated with epidemiological studies. Limited field collecting has generated
      host records and these have been added to a list of the aphids of Central America
      that was compiled by Pamela Anderson and appended in the guide with her
      permission. The authors hope that this book will be useful to entomologists in
      Costa Rica and Central America.

PMID- 15260170
TI  - A cognitive tool to diagnose predominantly inattentive ADHD behavior.
AB  - Poor performance on tests of reading comprehension could be the result of weak
      word-recognition skills, inconsistent attention (ADD), or a combination of the
      two. Identifying the source of the reading disability (RD) reliably has been
      difficult because inconsistent attention interferes with reading and weak word
      recognition skill makes attention wander. The situation is further complicated by
      the fact that there are no objective diagnostic tests for ADD (Breggin, 1998;
      Diller, 1998). We proposed a new model of differential diagnosis of ADHD-I/RD and
      field-tested its utility in two studies. The new diagnostic procedure utilizes
      intra-individual differences seen in the performance of at-risk learners on tasks
      related to reading that vary in the degree of sustained attention required for
      successful performance. The hypothesis is that children whose attention is
      inconsistent would perform more poorly on tests such as listening comprehension,
      which require sustained attention, than on tests such as reading comprehension,
      which are more tolerant of inattention. Such differences will not be seen in the
      test scores of children who have only a reading disability because their
      performance on reading tests is determined more by the difficulty level of the
      tests than by the sensitivity of the tests to attention. The validity of this new
      model was evaluated by determining the relationship between differences seen in
      the scores of tests that differ in their attention requirement and the degree of
      inconsistency in sustained attention as measured by Conners' CPT. The results of
      the two studies indicate this to be a viable approach. The results of the second
      study are presented in this report.

PMID- 15260171
TI  - Executive function and ADHD: a comparison of children's performance during
      neuropsychological testing and real-world activities.
AB  - OBJECTIVE: Current understanding of executive function deficits in Attention
      Deficit/Hyperactivity Disorder (ADHD) is derived almost exclusively from
      neuropsychological testing conducted in laboratory settings. This study compared
      children's performance on both neuropsychological and real-life measures of
      executive function and processing speed. METHOD: The Stroop and Wisconsin Card
      Sorting Task (WCST) were selected as neuropsychological measures, whereas route
      tasks in a videogame and at the zoo were used to index real-life measures.
      Participants comprised a community sample of 22 unmedicated boys with ADHD
      individually matched on age and IQ with 22 normally developing control boys.
      RESULTS: There were no group differences in executive function on the Stroop or
      zoo tasks, but the ADHD group exhibited deficits in set-shifting as assessed by
      the WCST (perseverative errors and responses) and videogame play (fewer
      challenges completed). Also, the ADHD group showed slowed processing speed on the
      Stroop (slower color naming) and zoo activity (longer time to complete task), as
      well as a slower rate of acquisition of the sorting rule on the WCST (more trials
      to complete first category). Efficient and flexible videogame play (number of
      challenges completed) was related positively to efficacy on the Stroop (number of
      items named correctly in the interference and two control conditions) and
      inversely related to set-shifting problems on the WCST (perseverative responses
      and errors). Also, problems in goal-directed behavior at the zoo (number of
      deviations from designated route) were related to problems in set-shifting on the
      WCST (perseverative responding). CONCLUSIONS: Children with ADHD exhibit
      impairments in executive function and processing speed in real-world activities
      as well as in neuropsychological testing. Cognitive deficits detected by
      standardized neuropsychological testing are related to performance difficulties
      in real-world activities.

PMID- 15260172
TI  - Knowledge and attitudes about attention-deficit hyperactivity disorder (ADHD): a
      comparison between practicing teachers and undergraduate education students.
AB  - The knowledge and attitudes of practicing teachers regarding ADHD were compared
      with those of undergraduate education students. Key elements of studies of
      American and Canadian teachers by Jerome, Gordon, and Hustler (1994) and Jerome,
      Washington, Laine, and Segal (1999) were replicated. Information was gathered
      about participants' demographic background (training in ADHD), attitudes towards
      ADHD, and knowledge about its diagnosis and treatment. Results confirmed the
      existence of some knowledge gaps, although both practicing teachers and
      undergraduate education students possessed sound information about ADHD.
      Misconceptions about ADHD primarily concerned dietary treatment. Attitudes and
      knowledge were significantly correlated and most participants regarded ADHD as a
      valid diagnosis with implications for the school setting, and expressed a desire
      for comprehensive training. Despite similar results for both samples, teachers
      achieved higher accuracy on knowledge-based questions. These results are
      discrepant from those of Jerome et al. (1999) who found teachers and students to
      be similar in factual knowledge. Implications of these findings for curriculum
      development in academia and in-service teacher training are highlighted.

PMID- 15260173
TI  - Quality of life of adolescent males with attention-deficit hyperactivity
      disorder.
AB  - Most psychosocial research on attention-deficit/hyperactivity disorder (ADHD) has
      focused on deficits in school, family, or behavioral functioning without
      incorporating perceived quality of life (QoL) or the adolescents' perspective.
      The Youth Quality of Life Instrument--Research Version (YQOL-R), was used to
      assess self-perceived QoL in a community sample of adolescents aged 11-18 years.
      Fifty-five adolescent males with a clinical diagnosis of ADHD were compared to a
      group of 107 adolescents with no chronic conditions (NCC) and a group of 52
      adolescents with mobility impairments (MI). The adolescents with ADHD reported
      significantly lower perceived QoL scores, particularly in the Self and
      Relationship domains, than the NCC group. Their scores were similar to those from
      the group with MI, a group previously shown to have a substandard QoL.
      Interventions to improve self-esteem and social interactions might use QoL
      outcomes in evaluating effectiveness.

PMID- 15260174
TI  - Harm and healing--militarism and peace.

PMID- 15260175
TI  - 'Iraq Water Treatment Vulnerabilities': a challenge to public health ethics.
AB  - A formerly classified US document, 'Iraq Water Treatment Vulnerabilities,'
      provides evidence that ill health was knowingly induced in the population of Iraq
      through the ruination of that country's water purification system. We believe
      that the uncovering of this document should stimulate the public health community
      to clarify principles of public health ethics and to formulate statements giving
      voice to these principles. We propose here two statements, one dealing with the
      broad issue of public health ethics and international relations, and one dealing
      specifically with public health ethics and water purification.

PMID- 15260176
TI  - Social contexts of trauma and healing.
AB  - The social contexts in which the mass trauma of thousands of people occur and in
      which their recovery should progress have qualities that distinguish it in
      important ways from individualised trauma in which a person is a victim of a
      violent attack, rape or a traffic accident. Organised violence, such as wars,
      oppression by dictatorships and massive terrorist attacks are extreme cases in
      which hundreds or thousands of people are exposed to trauma in a short period of
      time. As such, it has multiple consequences that extend beyond the affected
      individuals and the symptoms they suffer. Although the symptoms may be similar,
      the social contexts in which individual victimisation and exposure to organised
      violence happen are very different. The social milieu in which the survivors of
      individual trauma and survivors of mass trauma are embedded is likewise
      different, with important consequences for recovery. Understanding the social
      context of the trauma helps create the right social intervention for healing at
      social and personal levels.

PMID- 15260177
TI  - Psychosocial healing and post-conflict social reconstruction in the former
      Yugoslavia.
AB  - Post-conflict reconstruction encompasses social, physical and political
      reconstruction. Social reconstruction entails rebuilding the human interactions
      that allow a society to function. This involves the healing of psychological and
      social wounds of individuals and society. Psychosocial healing is a process to
      promote psychological and social health of individuals, families and community
      groups. The Medical Network for Social Reconstruction in the Former Yugoslavia
      has pioneered a broad range of psychosocial healing programmes including
      community-integration programmes, development of volunteer action, and training
      of professional and lay people to take part in psychosocial healing. These
      programmes have demonstrated that psychosocial healing can be an effective way to
      heal post-conflict societal trauma and contribute to rebuilding society with an
      improved quality of life.

PMID- 15260178
TI  - Family environment and emotional and behavioural symptoms in adolescent Cambodian
      Refugees: influence of time, gender, and acculturation.
AB  - For young refugees, the turmoil of adolescence is exacerbated by the
      acculturation process that sometimes places them at odds with the traditional
      culture of their ethnic group. The family environment can affect how adolescents
      cross that pivotal period. This paper focuses on the influence of family
      environment, gender and acculturation on the mental health of young refugees from
      early to mid-adolescence. Sixty-seven Cambodian adolescents were followed up from
      early to mid-adolescence. The effects of the youths' acculturation level, gender,
      and family environment and structure on internalising and externalising symptoms
      were analysed through linear regression analyses. Family conflict tends to
      increase from early to mid-adolescence. The association between family
      environment and mental health changes over time and, overall, family environment
      is associated with externalisation whereas gender, acculturation level, and
      family structure influence internalisation. Cambodian girls and boys cope
      differently with the challenges of adolescence in the host country, adopting
      traditional strategies and borrowing new ones from the host culture. Family
      therapy may help the parents and their adolescents address this process of
      change, which is both a source of vulnerability and of fulfilment, and enhances
      the ability of the family to negotiate between the cultural worlds of the home
      and of the host countries.

PMID- 15260179
TI  - Against the militarisation of Europe.

PMID- 15260180
TI  - Greek adaptation of EARS test battery.
AB  - Evaluation of Auditory Responses to Speech (EARS) is a test battery that was
      developed to measure the progress in the performance of children with cochlear
      implant. EARS was compiled in 1996 and is designed to assess hearing and speech
      perception skills in cochlear-implanted children. To date, the test battery has
      been adapted in 17 languages and is in use in various clinics worldwide. The aim
      of this study was to validate and determine the usability of a Greek EARS version
      in children with normal hearing. It was necessary to investigate whether the test
      items are appropriate for the language development in Greek children because of
      temporal and structural differences in language acquisition between Greek and
      English. Seventeen monolingual Greek children with normal hearing have been
      tested, aged 4 to 6 years, with the revised Greek version of EARS. The results
      pointed out the usability of EARS as an auditory test instrument for Greek
      children. Some materials and tasks had to be revised. The children had no
      difficulties with most of the subtests. In two of the seven subtests, children
      had some problems, perhaps due to their higher cognitive demand.

PMID- 15260181
TI  - Muscle activity in professional classical singing: a study on muscles in the
      shoulder, neck and trunk.
AB  - This study aimed to examine whether changes in the activity of shoulder and neck
      muscles have consequences for the activation of primary breathing muscles. It
      further aimed to compare muscle loading levels of professional and student
      singers. Four professional opera singers participated in the study. Previous
      unpublished recordings of 4 to 16 student singers and one opera singer were
      included to allow comparison of EMG loading levels between student and
      professional singers. Electromyographic (EMG) recordings of trapezius (TR),
      sternocleidomastoideus (STM), intercostals (INT), rectus abdominis (RC) and the
      lateral abdominal muscles (OBL) were performed. EMG biofeedback (BF) was
      performed on TR and STM to lower the activity in these two muscles and the
      potential change in EMG activity of INT, RC and OBL were examined. Three singing
      tasks were performed: aria, sustained tones and extreme tones. Each task was
      performed three times with variation in volume or pitch. Following the first
      performance of the singing tasks, the BF session was carried out and muscle
      activity recorded in a repeat performance of the same tasks. The EMG activity
      levels of all muscles were compared before and after BF. We found no significant
      effect of reduced TR/STM activity on the activation of INT, RC and OBL.
      Professional opera singers activated the TR, INT, RC and OBL muscles to higher
      levels than the student singers did. Another finding was large inter-subject
      variation in muscle usage, showing an idiosyncratic composition of the muscle
      contribution to subglottal pressure.

PMID- 15260183
TI  - Measuring the tuning accuracy of thousands singing in unison: an English Premier
      Football League table of fans' singing tunefulness.
AB  - Tunefulness in singing is well understood in the context of solo stage
      performance, singing in small groups and singing in choirs, with or without
      accompaniment, and it can be readily measured under laboratory conditions. When
      thousands of people are singing outside in support of their football team,
      however, the singing is impromptu; there is no conductor, no starting note, and
      generally no accompaniment. This paper describes the measurement of the
      tunefulness of the singing of fans of the twenty clubs in the 2001-2002 English
      Premier League. The technique adopted is unusual in that it makes direct
      reference to the formal definition of pitch as a subjective phenomenon. The
      results are presented in the form of a 2001-2002 English Premier League football
      fans singing league table.

PMID- 15260182
TI  - Effects of two-month vocal exercising with and without spectral biofeedback on
      student actors' speaking voice.
AB  - Twelve student actors (6 males, 6 females) were given voice training for two
      months. Randomly selected, half of the students (3 males, 3 females) was trained
      in the traditional way, while the other half was given biofeedback with real-time
      spectrum analysis. The aim was a ringing voice quality with strong overtones at 3
      5 kHz. Text samples read at different loudness levels were recorded before and
      after training. Fundamental frequency (F0), sound pressure level (SPL) and long
      term-average spectrum (LTAS) analyses were made. Voice quality was evaluated by
      two voice trainers. Sound energy at 3-5 kHz increased by 3-4 dB (1.5-14.5 dB)
      across groups after training. This change, which was slightly larger for the
      biofeedback (BF) group, did not correlate with SPL. F0 increased slightly in the
      BF group and decreased in the control group. The relative dB level of fundamental
      decreased significantly more in the BF group probably suggesting a tighter
      adduction. Voice quality improved in both groups. Visual feedback seems to add
      some efficacy in voice training. However, there is a danger of hyperfunctional
      voice production if other sensory feedback is neglected.

PMID- 15260184
TI  - Speech and voice analysis after near-total laryngectomy and tracheoesophageal
      puncture with implantation of Provox 2 prosthesis.
AB  - Vocal characteristics were compared in two groups of patients who were operated
      on due to laryngeal cancer. One group was composed of patients after near-total
      laryngectomy and the other after total laryngectomy followed by tracheoesophageal
      puncture with implantation of Provox 2 prosthesis. Acoustic analysis was carried
      out using the EZ Voice Plus program and included the following parameters:
      fundamental frequency, jitter, shimmer, harmonic to noise ratio, range of
      fundamental frequency, maximal phonation time and intensity.

PMID- 15260185
TI  - Comparison of alaryngeal voice and speech.
AB  - The aim of the research was to compare voice and speech in three groups of
      alaryngeal speakers: 1) patients using esophageal speech, 2) patients with
      electro-acoustical speech aids and 3) patients with voice prostheses. Acoustic
      analysis and pronunciation tests were used for the analysis. Acoustic analysis
      included fundamental frequency, maximum phonation time, jitter, shimmer and
      intensity. Pronunciation parameters were: phonetic block duration, number of
      syllables in a phonetic block, rate of speech, maximum number of syllables in a
      phonetic block and rate of articulation in a maximal phonetic block. Our results
      demonstrated the advantages of tracheoesophageal puncture with implantation of a
      voice prosthesis over the other two techniques of alaryngeal speech. Voice and
      pronunciation with voice prostheses were closer to normal in many parameters:
      fundamental frequency, maximum phonation time, jitter, shimmer, duration of a
      phonetic block, number of syllables in a phonetic block, rate of speech and rate
      of articulation in maximal phonetic block.

PMID- 15260186
TI  - Interdisciplinary voice examination (screening) for (choir) singers at the
      'Salzburger Sanger Service-Tag 2003'.

PMID- 15260187
TI  - Why is it difficult to see in the fog? How stimulus contrast affects visual
      perception and visual memory.
AB  - Processing visually degraded stimuli is a common experience. We struggle to find
      house keys on dim front porches, to decipher slides projected in overly bright
      seminar rooms, and to read 10th-generation photocopies. In this research, we
      focus specifically on stimuli that are degraded via reduction of stimulus
      contrast and address two questions. First, why is it difficult to process low
      contrast, as compared with high-contrast, stimuli? Second, is the effect of
      contrast fundamental in that its effect is independent of the stimulus being
      processed and the reason for processing the stimulus? We formally address and
      answer these questions within the context of a series of nested theories, each
      providing a successively stronger definition of what it means for contrast to
      affect perception and memory. To evaluate the theories, we carried out six
      experiments. Experiments 1 and 2 involved simple stimuli (randomly generated
      forms and digit strings), whereas Experiments 3-6 involved naturalistic pictures
      (faces, houses, and cityscapes). The stimuli were presented at two contrast
      levels and at varying exposure durations. The data from all the experiments allow
      the conclusion that some function of stimulus contrast combines multiplicatively
      with stimulus duration at a stage prior to that at which the nature of the
      stimulus and the reason for processing it are determined, and it is the result of
      this multiplicative combination that determines eventual memory performance. We
      describe a stronger version of this theory--the sensory response, information
      acquisition theory--which has at its core, the strong Bloch's-law-like assumption
      of a fundamental visual system response that is proportional to the product of
      stimulus contrast and stimulus duration. This theory was, as it has been in the
      past, highly successful in accounting for memory for simple stimuli shown at
      short (i.e., shorter than an eye fixation) durations. However, it was less
      successful in accounting for data from short-duration naturalistic pictures and
      was entirely unsuccessful in accounting for data from naturalistic pictures shown
      at longer durations. We discuss (1) processing differences between short- and
      long-duration stimuli, (2) processing differences between simple stimuli, such as
      digits, and complex stimuli, such as pictures, (3) processing differences between
      biluminant stimuli (such as line drawings with only two luminance levels) and
      multiluminant stimuli (such as grayscale pictures with multiple luminance
      levels), and (4) Bloch's law and a proposed generalization of the concept of
      metamers.

PMID- 15260188
TI  - Learning with arbitrary versus ecological conditioned stimuli: evidence from
      sexual conditioning.
AB  - Laboratory investigations of Pavlovian conditioning typically involve the
      association of an arbitrary conditioned stimulus (CS) with an unconditioned
      stimulus (US) that has no inherent relation to the CS. However, arbitrary CSs are
      unlikely to become conditioned outside the laboratory, because they do not occur
      often enough with the US to result in an association. Learning under natural
      circumstances is likely only if the CS has a preexisting relation to the US.
      Recent studies of sexual conditioning have shown that in contrast to an arbitrary
      CS, an ecologically relevant CS is resistant to blocking, extinction, and
      increases in the CS-US interval and results in sensitized responding and stronger
      second-order conditioning. Although the mechanisms of these effects are not fully
      understood, these findings have shown that signature learning phenomena are
      significantly altered when the kinds of stimuli that are likely to become
      conditioned under natural circumstances are used. The implications of these
      findings for an ecological approach to the study of learning are discussed.

PMID- 15260189
TI  - Configural and contextual prioritization in object-based attention.
AB  - When attention is directed to a location within an object, other locations within
      that object also enjoy an attentional advantage. Recently we demonstrated that
      this object-based advantage is mediated by increased attentional priority
      assigned to locations within an already attended object and not to early sensory
      enhancement due to the "spread" of attention within the attended object
      (Shomstein & Yantis, 2002). At least two factors might contribute to the
      assignment of attentional priority, one related to the configuration of objects
      in a scene and the other related to the probability of target appearance in each
      location imposed by task contingencies. We investigated the relative contribution
      of these factors by cuing one end of one of a pair of rectangles; a subsequent
      target appeared most often in the cued location. We manipulated attentional
      priority setting by varying (1) the probability that a target would appear in
      each of two uncued locations and (2) the cue to target stimulus onset asynchrony
      (SOA). On invalidly cued trials, the target appeared in the high-probability
      location (defined by an absolute spatial location, e.g., upper right) 83% of the
      time and in the low-probability location (e.g., lower left) 17% of the time. In
      both conditions, uncued targets appeared in the cued object half the time and in
      the uncued object half the time. At short SOAs, the same-object and probability
      effects were approximately additive. However, at longer SOAs, the same-object
      effects disappeared, and reaction times depended exclusively on location
      probability. These results suggest that observers adopt an implicit configural
      scanning strategy (in which unattended locations within an attended object have
      high priority) or an implicit contextual scanning strategy (in which objectively
      high-probability locations have high priority) depending on task contingencies
      and the amount of time that is available to deploy attention.

PMID- 15260190
TI  - The role of figure-ground segregation in change blindness.
AB  - Partial report methods have shown that a large-capacity representation exists for
      a few hundred milliseconds after a picture has disappeared. However, change
      blindness studies indicate that very limited information remains available when a
      changed version of the image is presented subsequently. What happens to the large
      capacity representation? New input after the first image may interfere, but this
      is likely to depend on the characteristics of the new input. In our first
      experiment, we show that a display containing homogeneous image elements between
      changing images does not render the large-capacity representation unavailable.
      Interference occurs when these new elements define objects. On that basis we
      introduce a new method to produce change blindness: The second experiment shows
      that change blindness can be induced by redefining figure and background, without
      an interval between the displays. The local features (line segments) that defined
      figures and background were swapped, while the contours of the figures remained
      where they were. Normally, changes are easily detected when there is no interval.
      However, our paradigm results in massive change blindness. We propose that in a
      change blindness experiment, there is a large-capacity representation of the
      original image when it is followed by a homogeneous interval display, but that
      change blindness occurs whenever the changed image forces resegregation of
      figures from the background.

PMID- 15260191
TI  - Warning: attending to a mask may be hazardous to your perception.
AB  - Object substitution is a type of backward masking that occurs when a mask appears
      during visual search for a target. We tested the hypothesis that object
      substitution is an overwriting process triggered by attentional selection of the
      mask. Impeding attentional selection of a mask by embedding it in an array of
      distractors eliminated object substitution. Similarly, object substitution did
      not occur when the mask appeared in advance of the target and, therefore, could
      not capture attention during search for the target. However, masking was
      reinstated when the mask was revealed from background contours at the moment of
      target onset and could therefore capture attention during search. These
      observations demonstrate that attentional selection of the mask is a necessary
      step in this type of masking and suggest that object substitution is active
      overwriting of unattended information triggered by selection of other visual
      information at a nearby location.

PMID- 15260192
TI  - Visual search is slowed when visuospatial working memory is occupied.
AB  - Visual working memory plays a central role in most models of visual search.
      However, a recent study showed that search efficiency was not impaired when
      working memory was filled to capacity by a concurrent object memory task
      (Woodman, Vogel, & Luck, 2001). Objects and locations may be stored in separate
      working memory subsystems, and it is plausible that visual search relies on the
      spatial subsystem, but not on the object subsystem. In the present study, we
      sought to determine whether maintaining spatial information in visual working
      memory impairs the efficiency of a concurrent visual search task. Visual search
      efficiency and spatial memory accuracy were both impaired when the search and the
      memory tasks were performed concurrently, as compared with when the tasks were
      performed separately. These findings suggest that common mechanisms are used to
      process information during difficult visual search tasks and to maintain spatial
      information in working memory.

PMID- 15260193
TI  - The role of spatial working memory in visual search efficiency.
AB  - Many theories have proposed that visual working memory plays an important role in
      visual search. In contrast, by showing that a nonspatial working memory load did
      not interfere with search efficiency, Woodman, Vogel, and Luck (2001) recently
      proposed that the role of working memory in visual search is insignificant.
      However, the visual search process may interfere with spatial working memory. In
      the present study, a visual search task was performed concurrently with either a
      spatial working memory task (Experiment 1) or a nonspatial working memory task
      (Experiment 2). We found that the visual search process interfered with a spatial
      working memory load, but not with a nonspatial working memory load. These results
      suggest that there is a distinction between spatial and nonspatial working memory
      in terms of interactions with visual search tasks. These results imply that the
      visual search process and spatial working memory storage require the same limited
      capacity mechanisms.

PMID- 15260194
TI  - Prioritizing new elements with a brief preview period: evidence against visual
      marking.
AB  - Watson and Humphreys (1997) have proposed that the ability to prioritize new
      elements over old elements involves a time-consuming process (of at least 400
      msec) of active inhibition of the locations of the old elements, which they
      referred to as visual marking. Recently, Donk and Theeuwes (2001) have suggested
      that prioritized selection of new over old elements is an instantaneous process
      related to the luminance change accompanying the appearance of the new elements.
      The aim of the present study was to test these two alternatives by investigating
      whether prioritized selection of new over old elements could be achieved with a
      very short preview of the old elements (50 msec). The results indicated that
      participants were able to prioritize selection of new over old elements when the
      new elements were presented with luminance onset whereas the old elements were
      not. New elements could not be prioritized if both the old and the new elements
      appeared with luminance onset. The results indicated that prioritization of new
      elements is based on an instantaneous process, rather than on a time-consuming
      process.

PMID- 15260195
TI  - Exploring the suffix effect in serial visuospatial short-term memory.
AB  - The suffix effect--the loss of recency induced by a redundant end-of-list item-
      was studied in a visuospatial serial recall task involving the memory for the
      position of dots on a screen. A visuospatial suffix markedly impaired recall of
      the last to-be-remembered dot. The impact on recall was roughly of equal
      magnitude whether the suffix shared attributes with the to-be-remembered dots
      (Experiment 1) or was visually distinct (Experiments 2 and 3). Although the
      presence of a tone suffix also impaired serial memory for the last items in the
      sequence, the impact of a visuospatial suffix was more marked, implying a
      specific as well as a possible general effect of suffix in the visuospatial
      domain (Experiment 4). The suffix effect seems not to be a phenomenon confined to
      verbal material but rather a universal phenomenon possibly related to grouping.

PMID- 15260196
TI  - When visual and verbal memories compete: evidence of cross-domain limits in
      working memory.
AB  - Recently, investigators have suggested that visual working memory operates in a
      manner unaffected by the retention of verbal material. We question that
      conclusion on the basis of a simple dual-task experiment designed to rule out
      phonological memory and to identify a more central faculty as the source of a
      shared limitation. With a visual working memory task in which two arrays of color
      squares were to be compared, performance was unaffected by concurrent recitation
      of a two-digit list or a known seven-digit sequence. However, visual working
      memory performance decreased markedly when paired with a load of seven random
      digits. This was not a simple tradeoff, inasmuch as errors on the visual array
      and high digit load tasks tended to co-occur. Working memory for digits and
      visual information thus are both subject to at least one type of shared limit,
      not just domain-specific limitations. The nature of the shared limit is
      discussed.

PMID- 15260197
TI  - Preparation for a forthcoming task is sufficient to produce subsequent shift
      costs.
AB  - Shifting from one task to another is associated with significant costs. Recently,
      it has been questioned whether the mere preparation for a forthcoming task,
      without the task's actually being executed, is sufficient to establish a new task
      set that results in shift costs when the execution of a task other than the
      prepared task is required. In a go/no-go study, it is shown that the mere
      preparation for a task is sufficient to produce shift costs, but only under
      conditions that encourage participants to engage in advance preparation for a
      precued task despite the possibility that the execution of this task will not
      always be required, because of occasional no-go trials. In addition, considerable
      reductions of shift costs after go trials could be observed under these
      conditions. When such a motivating context was not provided, only negligible
      shift costs were observed after a no-go trial, indicating that no task-set
      configuration had taken place without the need to perform the task. Furthermore,
      under these conditions, prolonging the preparation interval resulted in reaction
      time benefits that were similar for task shifts and repetitions, again indicating
      that no active task-set configuration took place.

PMID- 15260198
TI  - The redundant target effect is affected by modality switch costs.
AB  - When participants have to respond to stimuli of two modalities, faster reaction
      times are observed for simultaneous, bimodal events than for unimodal events (the
      redundant target effect [RTE]). This finding has been interpreted as reflecting
      processing gains for bimodal relative to unimodal stimuli, possibly due to
      multisensory interactions. In random stimulus sequences, reaction times are
      slower when the stimulus is preceded by a stimulus of a different modality
      (modality switch effect [MSE]). Simple reaction time redundant target experiments
      with auditory-visual, visual-tactile, and auditory-tactile stimulus combinations
      were run to determine whether the RTE may be partly explained by MSEs because
      bimodal stimuli do not require a modality switch. In all three modality pairings,
      significant MSEs and RTEs were observed. However, the RTE was still significant
      after reaction times were corrected for the MSE, supporting the hypothesis that
      coactivation occurs independently of modality switch costs.

PMID- 15260199
TI  - The accuracy of spatial information from temporally and spatially organized
      mental maps.
AB  - The way a space is learned can result in a mental map that is either temporally
      or spatially organized (Curiel & Radvansky, 1998). The present study examined the
      availability of spatial information under map learning conditions where either
      temporal or spatial organization has been previously observed. The finding was
      that people were fairly accurate in tasks that explicitly required the use of
      spatial information. However, there was a particular advantage for having a
      spatially organized mental map in a direction judgment task, especially for short
      distances where fine-grained knowledge was required. In contrast, there was no
      clear advantage for either group in a distance estimation task. These data are
      interpreted in the context of Huttenlocher's category adjustment model.

PMID- 15260201
TI  - Loading working memory enhances affective priming.
AB  - Stronger affective priming (Murphy & Zajonc, 1993) with suboptimal (i.e., reduced
      consciousness) than with optimal (i.e., full consciousness) prime presentation
      suggests that nonconscious processes form an important part of emotions. Merikle
      and Joordens (1997) have argued that both impoverished presentation and divided
      attention can produce suboptimal conditions and result in parallel effects. We
      manipulated attention by means of a concurrent working memory load while keeping
      presentation duration constant, as participants evaluated Japanese ideographs
      that were preceded by happy, neutral, or angry faces (affective priming) and male
      or female faces (nonaffective priming). In contrast to nonaffective priming,
      affective priming was larger with divided attention than with focused attention.
      It is concluded that manipulations of stimulus quality and of attention can both
      be used to probe the distinction between conscious and nonconscious processes and
      that the highest chances of obtaining the pattern of stronger priming with
      suboptimal presentation than with optimal presentation occur in the affective
      domain.

PMID- 15260200
TI  - Phonological representation of words in working memory during sentence reading.
AB  - The temporal dynamics of a visual target word's phonological representation was
      examined by presentation of an irrelevant spoken companion word when the
      participant's eyes reached the target's location during sentence reading. The
      spoken word was identical, similar, or dissimilar to the phonological
      specification of the visual target. All spoken words increased the time spent
      viewing the target, with larger effects in the similar and dissimilar spoken word
      conditions than in the identical condition. The reading of posttarget text was
      disrupted when the spoken word was similar but not when it was identical or
      dissimilar to the target. Phonological interference indicates that a word's
      phonological representation remains active after it has been identified during
      sentence reading.

PMID- 15260203
TI  - Spelling and dialect: comparisons between speakers of African American vernacular
      English and White speakers.
AB  - One characteristic of African American vernacular English (AAVE) is final
      obstruent devoicing, where the final consonant of a word like rigid is pronounced
      more like /t/ than /d/. To determine whether this dialect characteristic
      influences adults' spelling, African American and White college students spelled
      words such as rigid and ballot, pronounced by either a speaker of their own
      dialect or a speaker of the other dialect. African Americans, especially those
      who often devoiced final /d/, were more likely than Whites to confuse d and t.
      Both African American and White spellers made more d/t confusions when the words
      were spoken by an African American experimenter than by a White experimenter.
      Thus, the different phonological systems of AAVE and White speakers can cause
      them to make different types of spelling errors. Discussions of AAVE and literacy
      have focused on its syntax, but its phonology must also be considered.

PMID- 15260202
TI  - The ability of the saccadic system to change motor plans in scanning letter
      strings.
AB  - Evidence from recent studies bolsters the idea of preestablished motor plans in
      scanning isolated items. Thus, refixation saccades are preplanned at the same
      time as the primary saccade directed to a peripheral item and are completed with
      fixed amplitudes irrespective of the first fixation position in the item. In
      order to examine the saccadic system's ability to correct the motor plan during
      its execution on the basis of new visual information, an experiment was conducted
      in which 11-letter strings were changed to two 5-letter strings at different
      times after the primary saccade was directed to the stimulus. The results
      demonstrate that the saccadic system is able to cancel the preplanned refixation
      saccade and plan a saccade directed to the next item only when the new visual
      information is available at least 220 msec before the execution of the saccade.

PMID- 15260204
TI  - Evidence accumulation in decision making: unifying the "take the best" and the
      "rational" models.
AB  - An evidence accumulation model of forced-choice decision making is proposed to
      unify the fast and frugal take the best (TTB) model and the alternative rational
      (RAT) model with which it is usually contrasted. The basic idea is to treat the
      TTB model as a sequential-sampling process that terminates as soon as any
      evidence in favor of a decision is found and the rational approach as a
      sequential-sampling process that terminates only when all available information
      has been assessed. The unified TTB and RAT models were tested in an experiment in
      which participants learned to make correct judgments for a set of real-world
      stimuli on the basis of feedback, and were then asked to make additional
      judgments without feedback for cases in which the TTB and the rational models
      made different predictions. The results show that, in both experiments, there was
      strong intraparticipant consistency in the use of either the TTB or the rational
      model but large interparticipant differences in which model was used. The unified
      model is shown to be able to capture the differences in decision making across
      participants in an interpretable way and is preferred by the minimum description
      length model selection criterion.

PMID- 15260206
TI  - Perceptual specificity of priming for compound words not presented.
AB  - Two experiments extended prior work on the perceptual specificity of priming to
      compound words not presented during a study phase. In both experiments,
      perceptual manipulations were employed, and priming was obtained on a word
      fragment completion test (e.g., c_ec_po_nt) where the lexical elements of the
      compounds (check and point) were presented in different study words. In
      Experiment 1, priming was highest when identical fragments for the lexical
      components were presented during the study phase (c_ec_list, needlepo_nt) and
      test phase (c_ec po_nt). In Experiment 2, visual study presentations, but not
      auditory study presentations, led to significant priming. The findings are
      consistent with predictions from transfer-appropriate processing and demonstrate
      perceptual, not lexical (post-perceptual), priming.

PMID- 15260205
TI  - One process is not enough! A speed-accuracy tradeoff study of recognition memory.
AB  - Speed-accuracy tradeoff (SAT) methods have been used to contrast single- and dual
      process accounts of recognition memory. In these procedures, subjects are
      presented with individual test items and are required to make recognition
      decisions under various time constraints. In this experiment, we presented word
      lists under incidental learning conditions, varying the modality of presentation
      and level of processing. At test, we manipulated the interval between each
      visually presented test item and a response signal, thus controlling the amount
      of time available to retrieve target information. Study-test modality match had a
      beneficial effect on recognition accuracy at short response-signal delays (< or
      =300 msec). Conversely, recognition accuracy benefited more from deep than from
      shallow processing at study only at relatively long response-signal delays (> or
      =300 msec). The results are congruent with views suggesting that both fast
      familiarity and slower recollection processes contribute to recognition memory.

PMID- 15260207
TI  - Memory for actions: enactment and source memory.
AB  - Enacting simple action phrases enhances item memory but may not enhance other
      aspects of memory. The present experiment examines the effects of enactment on
      source memory. During the study phase, participants performed some actions
      (subject-performed tasks, SPTs) and observed the experimenter perform other
      actions (experimenter-performed tasks, EPTs). One group performed the SPTs with
      eyes closed, one group with eyes open (the standard condition), and one group
      performed SPTs facing a mirror (EPT presentation was constant across groups). As
      expected, item memory was better for SPTs than for EPTs. More importantly, source
      memory for SPTs was affected by the amount of visual feedback. As predicted by
      the source-monitoring framework, source memory for SPTs decreased as the amount
      of visual feedback increased from none (eyes closed) to moderate (standard
      condition) to maximal (mirror condition). In addition, SPT encoding failed to
      increase source memory and in one condition actually decreased source memory,
      relative to EPT encoding. Thus, enactment dissociated item and source memory,
      enhancing the former but not the latter.

PMID- 15260208
TI  - Haste does not always make waste: expertise, direction of attention, and speed
      versus accuracy in performing sensorimotor skills.
AB  - In two experiments, we examined the attentional mechanisms governing sensorimotor
      skill execution across levels of expertise. In Experiment 1, novice and expert
      golfers took a series of putts under dual-task conditions designed to distract
      attention from putting and under skill-focused conditions that prompted attention
      to step-by-step performance. Novices performed better under skill-focused than
      under dual-task conditions. Experts showed the opposite pattern. In Experiment 2,
      novice and expert golfers putted under instructions that emphasized either
      putting accuracy or speed--the latter intended to reduce the time available to
      monitor and explicitly adjust execution parameters. Novices putted better under
      accuracy instructions. Experts were more accurate under speed instructions. In
      agreement with theories of skill acquisition and automaticity, novice performance
      is enhanced by conditions that allow for on-line attentional monitoring (e.g.,
      skill-focused or accuracy instructions) in comparison with conditions that
      prevent explicit attentional control of skill execution (e.g., dual-task or speed
      constraints). In contrast, the proceduralized skill of experts benefits from
      environments that limit, rather than encourage, attention to execution.

PMID- 15260209
TI  - Strategic processes in false recognition memory.
AB  - In two experiments, the response signal technique (Reed, 1973) was combined with
      the DRM paradigm (e.g., McDermott & Roediger, 1998) to investigate the time
      course of false recognition memory--in particular, how this effect varies along
      the time course of generating a recognition judgment. Across the experiments, in
      addition to standard instructions, there were forewarning instructions
      encouraging the participants to avoid this effect, as well as inclusion
      instructions intended to enhance this tendency. It was found that the false
      memory effect was at its strongest at earlier response signals, diminishing when
      more time was given to make a recognition judgment. The forewarning instructions
      led to a more conservative overall response bias, rather than to a reduction of
      the effect. However, the participants were able to exaggerate this effect in the
      inclusion condition. The results are discussed in terms of the role of strategic
      processing in recognition memory.

PMID- 15260210
TI  - Social identity and community effects on contraceptive use and intentions in
      southern Ethiopia.
AB  - In this study, data gathered in southern Ethiopia are used to explain how ethnic
      and religious identities affect current or intended contraceptive use. The only
      compositionalfactors that increase the likelihood of birth limitation are having
      a member of the family with a higher level of education and community access to
      health services. Compositional factors by themselves do not explain Muslim and
      ethnic variations in contraceptive use and intentions. Village health and
      economic crises do not promote birth limitation. One normative economic factor-
      the practice of sons' inheritance of land from their fathers--considerably
      reduces the likelihood of contraceptive use, but does not account for religious
      and ethnic differentials. No evidence is found of a minority-status effect on
      contraception. Exposure to ethnic and religious diversity in the community of
      residence substantially increases the likelihood of emergent birth limitation,
      especially among the predominant Muslim Silte population.

PMID- 15260211
TI  - Factors associated with contraceptive use in late- and post-apartheid South
      Africa.
AB  - In 1994, South Africa underwent a transition from the institutionalized racism of
      an apartheid state to a nonracial democracy. This study uses data from two
      surveys conducted in the style of the Demographic and Health Surveys to compare
      patterns and predictors of racial differences in modern contraceptive use in the
      late- and post-apartheid periods. Age-group-specific logistic regression models
      show that despite strong state family planning programs targeting black women,
      these women were less likely than nonblacks to practice modern contraception both
      before and after the political transition, even after controlling for large
      racial-group differences in sociodemographic characteristics and the distribution
      of socioeconomic resources. Black, colored, Indian, and white women show
      different patterns of contraceptive use across their reproductive careers; in
      particular, young, unmarried black and colored women show high levels of use. Use
      of injectable contraceptives is also high among black and colored women, whereas
      injectables are not the primary method used by Indian or white women. These
      findings are discussed in light of their research and policy implications.

PMID- 15260212
TI  - The moral lens of population control: condoms and controversies in southern
      Malawi.
AB  - The study presents an investigation of stories about condoms in southern Malawi.
      Malawians' concerns about coercive population control imposed by a national
      government or international cabal provide a moral lens through which condoms and
      other health promotions are viewed, with unknown but probably negative impact on
      the use of condoms. The focus of the study is on the long shadow cast by
      population control because it is underresearched and, in fact, virtually
      unmentioned in most studies of health promotion, yet appears to be common if not
      ubiquitous. Moreover, this long shadow poses a distinct challenge to HIV
      prevention and intervention efforts. The data for the study were gathered by six
      Malawian research assistants in Balaka district, in southern Malawi, who kept
      journals over a period of three years in which they recorded conversations and
      everyday chats that they observed. These journals demonstrate that condoms do not
      arrive in communities as neutral, value-free objects; rather they enter a social
      setting permeated with ideas about health, self-protection, and danger. The lens
      of population control has proved to be both durable and flexible, providing a
      moral context in which both commodities and actors can be understood.
      Disentangling condoms from the symbolic nexus in which they are fused with
      disease, population control, and malevolence will be an ongoing challenge in the
      struggle to prevent the spread of HIV/AIDS in Malawi.

PMID- 15260213
TI  - Condom use within marital and cohabiting partnerships in KwaZulu-Natal, South
      Africa.
AB  - Traditionally, the major focus of condom-promotion strategies has been on
      increasing use outside marriage. This study explores the extent and determinants
      of condom use within marital and cohabiting partnerships in KwaZulu-Natal, South
      Africa. In focus-group discussions, in-depth interviews, and individual survey
      responses, knowledge of condoms as an effective method of dual protection against
      the risk of pregnancy and disease was found to be high. Consistent with numerous
      other studies, this study found widespread disapproval of condom use within
      marriage. Only 14 percent of men and 17 percent of women reported consistent or
      "occasional" condom use. Nevertheless, condom use is much higher among urban,
      more-educated individuals than among their rural, less-educated counterparts.
      Apart from education, perceived risk of HIV infection from the partner is the
      most powerful determinant of use within marital and cohabiting partnerships,
      particularly for women. Resistance to condoms within marital and cohabiting
      partnerships is not immutable, however, and women may not be as powerless to
      protect themselves as is often reported.

PMID- 15260215
TI  - Mauritania 2000-2001: results from the demographic and health survey.

PMID- 15260214
TI  - Relationships between older men and younger women: implications for STIs/HIV in
      Kenya.
AB  - The aim of this study is to contribute to the understanding of motivations for
      cross-generational relationships and how the perception of risk of acquiring
      sexually transmitted infections (STIs) including HIV affects condom use in Kenya.
      Eight focus-group discussions were conducted with women and 28 interviews were
      held with men in four Kenyan towns. Ethnograph 5.0 computer software was used for
      the analysis of data. Women's primary incentive for engaging in such
      relationships is financial; men seek sexual gratification. Pressure from peers
      compels women to find older partners. Although some peers encourage such
      relationships, other groups, especially wives, same-aged boyfriends, and parents,
      disapprove of them. Couples are preoccupied by the threat of discovery. STI/HIV
      risk perception is low, and couples rarely use condoms. Material gain, sexual
      gratification, emotional factors, and recognition from peers override concern for
      STI/ HIV risk. Women's ability to negotiate condom use is compromised by age and
      economic disparities. Programmatic strategies include communicating information
      about such relationships' STI/HIV risk, promoting consistent condom use,
      decreasing peer pressure to pursue such relationships, and improving women's
      access to alternative sources of income.

PMID- 15260216
TI  - Nepal 2001: results from the demographic and health survey.

PMID- 15260217
TI  - Earthworms and litter distribution affect plant-defensive chemistry.
AB  - Studies on plant-defensive chemistry have mainly focused on plants in direct
      interaction with aboveground and occasionally belowground herbivores and
      pathogens. Here we investigate whether decomposers and the spatial distribution
      of organic residues in soil affect plant-defensive chemistry. Litter concentrated
      in a patch (vs. homogeneously mixed into the soil) led to an increase in the
      aucubin content in shoots of Plantago lanceolata. Earthworms increased total
      phytosterol content of shoots, but only when the litter was mixed homogeneously
      into the soil. The phytosterol content increased and aphid reproduction decreased
      with increasing N concentration of the shoots. This study documents for the first
      time that earthworms and the spatial distribution of litter may change plant
      defensive chemistry against herbivores.

PMID- 15260219
TI  - Differences among antimicrobial properties of carrion beetle secretions reflect
      phylogeny and ecology.
AB  - Carrion beetles (Coleoptera: Silphidae) consist of two subfamilies in North
      America. Members of the Silphinae arrive at carcasses during the mid-stage of
      decay and their larvae feed on developing maggots, while members of the
      Nicrophorinae bury and tend carcasses upon which their developing larvae feed.
      The Nicrophorinae maintain the condition of the carcass by applying oral and anal
      secretions that reduce carcass decay apparently through bacterial inhibition,
      although quantification has not been made. We hypothesized that enzymes in the
      oral and anal secretions of the subfamily Nicrophorinae would inhibit bacterial
      growth, while secretions from the subfamily Silphinae would not. The secretions
      were assayed for inhibitory effects with a Microtox Analyzer that monitors the
      decrease in bioluminescence from the bacterium Vibrio fischerii. We found a
      significant difference of bioluminescence in the control compared to secretions
      of 8 out of 10 tested Nicrophorinae (with oral secretions being most active),
      while only anal secretions from Necrodes surinimensis of the Siphinae
      significantly reduced bacterial survival. These data follow the known phylogenic
      relationship in which Necrodes is the closest genus to the Nicrophorinae. The two
      species of Nicrophorinae, which did not show significant reductions in bacterial
      growth, differ ecologically from the others. Thus, the presence of antimicrobial
      compounds in most Nicrophorinae secretions, but not in most other Silphinae,
      represents an adaptation to preserve the buried carcass.

PMID- 15260218
TI  - Semiochemicals from fungal associates of bark beetles may mediate host location
      behavior of parasitoids.
AB  - In laboratory olfactometer bioassays, females of two hymenopteran parasitoid
      species, Roptrocerus xylophagorum (Ratzeburg) (Hymenoptera: Pteromalidae) and
      Spathius pallidus (Ashmead) (Hymenoptera: Braconidae), were attracted to odors
      from bark or bolts of loblolly pine, Pinus taeda L., colonized by bluestain fungi
      (genus Ophiostoma) associated with the parasitoids' bark beetle hosts. Mock
      inoculated bolts and bark were less attractive or unattractive in these
      bioassays. Bark infested with host larvae that lacked their fungal and other
      normal microbial associates was attractive to R. xylophagorum females, but was
      less so than bark infested with larvae possessing their normal complement of
      associated microbes. In contrast, in oviposition bioassays, R. xylophagorum
      females spent approximately equal time searching, made similar numbers of
      oviposition attempts, parasitized similar percentages of hosts, and laid similar
      numbers of eggs in bark fragments infested with either associate-free or
      associate-bearing host larvae. Furthermore, in field bioassays using bluestain
      inoculated or mock-inoculated loblolly pine bolts as sources of attractants, the
      numbers of parasitoids attracted by the two treatments did not differ
      significantly and the two treatments were less attractive than bolts naturally
      infested with bark beetle larvae. Whereas our laboratory olfactometer data
      suggest that bark beetle fungal associates may enhance attraction of some
      parasitoids, our bioassays with associate-free hosts indicate that associate
      produced are not required for short-range host location and parasitization. In
      addition, our field trials indicated that long-range attraction of parasitoids to
      the host-fungi-tree complex is not caused simply by an interaction between
      bluestain fungi and tree tissues.

PMID- 15260220
TI  - Quinone mixture as attractant for necrophagous dung beetles specialized on dead
      millipedes.
AB  - 2-Methyl-1,4-benzoquinone (toluquinone) and 2-methoxy-3-methyl-1,4-benzoquinone
      are the most common components of defensive secretions of juliform millipedes
      (Diplopoda: Juliformia). A natural and a synthetic millipede-defensive secretion
      composed of these two substances attract dung beetles of a few Onthophagus
      species (Coleoptera: Scarabaeidae) that feed mainly on freshly dead millipedes.
      This olfactory mechanism and adaptation to the toxic effects of quinones enables
      them to be the first and exclusive users of this resource.

PMID- 15260221
TI  - Olfactory responses to aphid and host plant volatile releases: (E)-beta-farnesene
      an effective kairomone for the predator Adalia bipunctata.
AB  - The volatiles released from several aphid and host plant species, alone or
      associated, were studied for their infochemical role in prey location. Using a
      four-arm olfactometer, the attraction of several combinations of three aphid
      (Myzus persicae, Acyrthosiphon pisum, and Brevicoryne brassicae) and three plant
      (Vicia faba, Brassica napus, and Sinapis alba) species toward Adalia bipunctata
      larvae and adults was observed. Both predatory larvae and adults were attracted
      only by A. pisum and M. persicae when they were crushed, whatever the host plant.
      (E)-beta-farnesene, the aphid alarm pheromone, was the effective kairomone for
      the ladybird. Plant leaves alone (V. faba, B. napus, and S. alba) or in
      association with nonstressed whole aphids (the three species) did not have any
      attraction for the predator. The B. brassicae specialist aphid is the only prey
      that was not attracted to A. bipunctata larvae and adults, even if they were
      crushed. Release of B. brassicae molecules similar to the host plant
      allelochemicals was demonstrated by GC-MS analysis. The lack of behavioral
      response of the ladybird at short distance toward the cruciferous specialist
      aphid was related only to the absence of (E)-beta-farnesene in the aphid prey
      volatile pattern.

PMID- 15260222
TI  - Constraint of feeding by chronic ingestion of 1,8-cineole in the brushtail possum
      (Trichosurus vulpecula).
AB  - Eucalyptus leaf-eating marsupials such as the brushtail possum (Trichosurus
      vulpecula) ingest large amounts of terpenes, especially 1,8-cineole (cineole)-
      the major component of many eucalyptus oils. Brushtail possums were acclimated to
      a non-Eucalyptus diet with increasing concentrations of cineole (0.5-4.0% wet
      weight) added over 18 d. We measured food and cineole consumption and urinary
      metabolites of cineole. Food intake decreased with cineole content, indicating
      that it was constrained by the maximum tolerable intake of cineole that was 3.8
      +/- 0.2 g kg(-1) or 5.2 +/- 0.3 g kg(-0.75) (mean +/- SE, N = 6). The pattern of
      metabolites was similar at all cineole intakes (56% hydroxycineolic acids, 27%
      cineolic acids, 13% hydroxycineoles, and 4% dihydroxycineoles). In another
      experiment, possums maintained on artificial diet were abruptly presented with 4%
      cineole for 5 d. Food intake fell by 45 +/- 6% (mean +/- SE, N = 6) and mean
      cineole intake was 2.9 +/- 0.3 g kg(-1). There was evidence of induction of
      secondary oxidative pathways, as hydroxycineoles were the major metabolites (48%
      total) on the first day, but rapidly dropped to 15% on subsequent days as the
      acid metabolites increased. These findings indicate that ingestion of cineole is
      not constrained by selective saturation of individual enzymes involved in its
      multiple pathways of oxidation, but rather the total detoxification capacity
      appears to limit feeding on a cineole diet.

PMID- 15260223
TI  - Male urinary chemosignals differentially affect aggressive behavior in male mice.
AB  - Chemical signals modulate aggressive behavior in mice. For example, male urinary
      cues enhance aggression against other adults: a resident mouse attacks a male but
      not a castrated intruder, unless it is anointed with male urine. Our purpose was
      to understand whether molecules excreted with urine also act as aggression
      triggers in a different context. Therefore, the effect of urine, or molecules
      purified from urine, voided by different animals (males or females), was tested
      on the aggression of male mice against pups. Latency to the first attack,
      percentage of pups receiving the first attack, and percentage of attacked pups
      after 5 and 15 min were recorded. At variance with intermale aggression, male
      urinary chemosignals sprayed on pups reduced infanticide, while female urine did
      not. Male urine also delayed infanticide when compared to female urine. Pups
      anointed with low molecular weight dialyzed urine and with the high molecular
      weight protein fraction were attacked later than controls. Pups anointed with
      Major Urinary Proteins (MUPs) also were attacked later. The volatiles retained by
      MUPs act in the same way as adult male urine. MUPs and their ligands did not
      modify biting of food items. The results show that mice do not perceive male
      chemosignals as compulsory aggression triggers but rather can consistently and
      differentially shape their behavior in response to the same molecules according
      to different contextual events.

PMID- 15260224
TI  - A stingless bee (Melipona seminigra) marks food sources with a pheromone from its
      claw retractor tendons.
AB  - By depositing scent marks on flowers, bees reduce both the search time and the
      time spent with the handling of nonrewarding flowers. They thereby improve the
      efficiency of foraging. Whereas in honey bees the source of these scent marks is
      unknown, it is assumed to be the tarsal glands in bumble bees. According to
      histological studies, however, the tarsal glands lack any openings to the
      outside. Foragers of the stingless bee Melipona seminigra have previously been
      shown to deposit an attractant pheromone at sugar solution feeders, which is
      secreted at the tips of their tarsi. Here we show that the claw retractor tendons
      have specialized glandular epithelia within the femur and tibia of all legs that
      produce this pheromone. The secretion accumulates within the hollow tendon, which
      also serves as the duct to the outside, and is released from an opening at the
      base of the unguitractor plate. In choice experiments, M. seminigra was attracted
      by feeders baited with pentane extracts of the claw retractor tendons in the same
      way as it was attracted by feeders previously scent marked by foragers. Our
      results resolve the seeming contradiction between the importance of foot print
      secretions and the lack of openings of the tarsal glands.

PMID- 15260225
TI  - New type of Sesiidae sex pheromone identified from the hornet moth Sesia
      apiformis.
AB  - Two components of the female-produced sex pheromone of the hornet moth, Sesia
      apiformis, were identified as (3Z,13Z)-octadeca-3,13-dien-1-ol (3Z,13Z-18:OH) and
      (2E,13Z)-octadeca-2,13-dienal (2E,13Z-18:Al), a pheromone structure new in
      Sesiidae. Pooled gland extracts showed the two major compounds in a proportion of
      ca. 2:3, while SPME-investigations on single calling females revealed a ratio of
      ca. 1:7. Although the single compounds were not attractive, a 2:3 mixture proved
      to be highly active towards males in field tests. Small amounts of (2E,13Z)
      octadecadienol (2E,13Z-18:OH) were found in the sex pheromone gland of females,
      however, the biological significance of the compound remains unclear. Methyl
      sulfide was found to readily react with 2-alkenals, providing an effective new
      method for the characterization of this type of compound upon GC/MS. The
      derivatives, 1,1,3-tris(methylthio)alkanes, are the products of the addition of
      methyl sulfide to the double bond and the transformation of the carbonyl group
      into the corresponding bis(methylthio)acetal. The mass spectra of these compounds
      are characterized by diagnostic signals at m/z 107 and/or m/z 121. These
      fragments represent the first carbon unit or the first two carbon units of the
      derivative, respectively. The parent signal in the spectra of thiomethyl
      derivatives of 2-alkenals showing no other double bonds is represented by m/z M+ 
      121, formed upon loss of the first two carbon units. By employing a solution of
      methyl sulfide in dimethyl sulfide, the double bond positions in 2E,13Z-18:Al
      could be fully characterized by GC/MS.

PMID- 15260226
TI  - Identification of two sex pheromone components of the potato aphid, Macrosiphum
      euphorbiae (Thomas).
AB  - Females of the potato aphid Macrosiphum euphorbiae exhibit typical calling
      behavior, with virgin female oviparae raising their back legs off the substrate
      to release sex pheromone from glands on the tibia. Airborne collections from
      calling oviparae were analyzed by GC and GC-MS to determine if, like the majority
      of aphids examined to date, they produced (1R,4aS,7S,7aR)-nepetalactol (1) and
      (4aS,7S,7aR)-nepetalactone (2). Both components were present and produced in
      ratios that varied with age from 4:1 to 2:1. The relative stereochemical
      configurations of these components were determined by GC-coinjection of the aphid
      derived sample with synthetic standards on both HP-1 and DB-Wax GC columns. The
      absolute stereochemical configuration of the nepetalactol (determined from
      approximately 15 microg of material in an air entrainment sample) was determined
      as (1R,4aS,7S,7aR)-1 by derivatization of the aphid sample with (S)-(+)-alpha
      methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (Mosher's acid chloride) to
      generate a diastereoisomer that was compared to synthetic samples by NMR
      spectroscopy and GC. In bioassays in the wind tunnel, M. euphorbiae males
      responded to potato plants with oviparae but not to unattacked plants or those
      infested with parthenogenetically reproducing apterae. In no-choice laboratory
      bioassays, the same level of male response was observed to virgins and to the 3:1
      5:1 synthetic blends of nepetalactol (1):nepetalactone (2). However, the time
      taken to reach the source was significantly less to virgin females than to the
      synthetic pheromone blends. In all cases, males walked rather than flew to the
      source. Males showed lower responses to a 1:1 synthetic mixture and did not
      respond to either of the components when presented alone. Under field conditions,
      few M. euphorbiae males were captured in traps baited with different ratios of
      the synthetic pheromone. Possible reasons for the different responses under
      laboratory and field conditions are discussed.

PMID- 15260227
TI  - Trilinolein identified as a sex-specific component of tergal glands in alates of
      Coptotermes formosanus.
AB  - Hexane extracts of the tergal glands from female alates of the Formosan
      subterranean termite Coptotermes formosanus were analyzed by high performance
      liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry
      with collision-induced dissociation. Double bond configuration was determined by
      chemical modifications with gas chromatography-mass spectrometry. A single
      component, identified as the triacylglycerol, trilinolein, was unique to the
      female tergal glands. This compound was not found in other areas of the female
      alate abdomen or in the corresponding area of male alates. Neither gland extract
      nor trilinolein caused a behavioral response from male alates. However,
      significant differences were found between males and females for responses from
      neurons within sensilla of the maxillary palps.

PMID- 15260228
TI  - Composition of chemical attractants affects trap catches of the Australian sheep
      blowfly, Lucilia cuprina, and other blowflies.
AB  - Numbers of Lucilia cuprina (Australian sheep blowfly), Chrysomya spp., and
      Calliphora spp. blowflies caught on sticky traps baited with various synthetic
      attractants or a standard liver/sodium sulfide attractant in western Queensland
      were recorded. Numbers of each genus collected were influenced by the composition
      of the chemical attractants. Attractant mixtures based on 2-mercaptoethanol,
      indole, butanoic/pentanoic acid, and a sodium sulfide solution gave 5- to 20-fold
      higher L. cuprina catches than the liver standard. These blends attracted similar
      numbers of Chrysomya spp. (0.85-2.7x) and fewer Calliphora spp. (0.02-0.2x)
      compared to the liver standard. These synthetic attractants were more effective
      and selective for L. cuprina than the standard liver/sodium sulfide attractant,
      and they can be packaged in controlled-release dispensers to generate constant,
      prolonged release of the attractant.

PMID- 15260229
TI  - Bioactivity of phenanthrenes from Juncus acutus on Selenastrum capricornutum.
AB  - Twenty-five 9,10-dihydrophenanthrenes, four phenanthrenes, a dihydrodibenzoxepin,
      and a pyrene, isolated from the wetland plant Juncus acutus, were tested to
      detect their effects on the green alga Selenastrum capricornutum. Nine of the
      compounds were isolated and identified for the first time. Most of the compounds
      caused inhibition of algal growth. The 9,10-dihydrophenanthrenes 1, 5, 21, and 22
      were the most active.

PMID- 15260231
TI  - Genotyping by mass spectrometry.

PMID- 15260230
TI  - Colorado potato beetle toxins revisited: evidence the beetle does not sequester
      host plant glycoalkaloids.
AB  - The Colorado potato beetle feeds only on glycoalkaloid-laden solanaceous plants,
      appears to be toxic to predators, and has aposematic coloration, suggesting the
      beetle may sequester alkaloids from its host plants. This study tested 4th
      instars and adults, as well as isolated hemolymph and excrement, to determine if
      the beetles sequester, metabolize, or excrete alkaloids ingested from their host
      plants. HPLC analysis showed: that neither the larvae nor the adults sequestered
      either solanine or chaconine from potato foliage; that any alkaloids in the
      beetles were at concentrations well below 1 ppm; and that alkaloids were found in
      the excrement of larvae at approximately the same concentrations as in foliage.
      Analysis of alkaloids in the remains of fed-upon leaflet halves plus excreta
      during 24 hr feeding by 4th instars, as compared to alkaloids in the uneaten
      halves of the leaflets, showed that equal amounts of alkaloids were excreted as
      were ingested. The aposematic coloration probably warns of a previously
      identified toxic dipeptide instead of a plant-derived alkaloid, as the Colorado
      potato beetle appears to excrete, rather than sequester or metabolize, the
      alkaloids from its host plants.

PMID- 15260232
TI  - Development of targeted viral vectors for cardiovascular gene therapy.

PMID- 15260233
TI  - Practical applications of rolling circle amplification of DNA templates.
AB  - Since its recent implementation at one of the world's largest high-throughput
      sequencing centers, the utility of MP-RCA for DNA sequencing has been thoroughly
      validated. However, applications of this technology extend far beyond DNA
      sequencing. While many of these applications have been explored in this chapter,
      the future will undoubtedly add to this growing list.

PMID- 15260234
TI  - Structural analyses of living plant nuclei.
AB  - The nucleus is the cellular organelle in which the bulk of the genomic
      information is stored. From studies using fluorescence microscopy with optical
      sections of fixed cells, a picture of an organized nuclear structure has emerged.
      Recently, the application of the green fluorescent protein (GFP) as a fluorescent
      dye allows the visualization of nuclear dynamics in live cells. Using four
      dimensional fluorescence microscopy, the nuclear structures within an interphase
      nucleus are perceived to have dynamic domains. Structural analyses of a living
      plant nucleus contribute to our understanding of the genome information process
      in a particular cell in multicelluar systems.

PMID- 15260235
TI  - Bacterial ion channels.

PMID- 15260236
TI  - Functional analysis of promoter elements in plants.

PMID- 15260237
TI  - Applications of plant antiviral proteins.

PMID- 15260239
TI  - Delitto perfetto targeted mutagenesis in yeast with oligonucleotides.

PMID- 15260238
TI  - Biosynthesis and metabolism of glutathione in plants.

PMID- 15260240
TI  - The bacterial scaffoldin: structure, function and potential applications in the
      nanosciences.
AB  - Natural protein complexes may provide the best templates for nanometer-scale
      technology and new biomaterials. The bacterial cellulosome is becoming a well
      understood multi-protein complex found in cellulolytic microorganisms. The
      scaffoldin subunits of the bacterial cellulosome function to organize and
      position other protein subunits into the complex. The scaffoldins can also serve
      as an attachment device for harnessing the cellulosome onto the cell surface
      and/or for its targeting to substrate. Biochemical and molecular biological
      evidence have identified a receptor/adaptor type of protein domain pair, called
      "cohesin and dockerin," which is responsible for cellulosome self-assembly. The
      recognition between cohesin and dockerin is generally type and/or species
      specific. More than 80 cohesin and 100 dockerin sequences have been found, mostly
      from anaerobic bacteria. X-ray crystallography and NMR have been used to
      determine the three-dimensional structures of representative cohesin and dockerin
      domains, respectively. The cohesin peptide is about 140 amino acids in length and
      highly conserved in sequence and domain structure. The dockerin domain comprises
      about 70 amino acids and contains two 22 amino acid duplicated regions, each of
      which includes an "F-hand" modification of the EF-hand calcium-binding motif.
      Biochemical evidence and site-directed mutagenesis have confirmed that the two F
      hand motifs are required for function and calcium dependence; at least two amino
      acids from each motif are critical for cohesin-dockerin recognition. In this
      report, we review the structure and function of the scaffoldin of the bacterial
      cellulosome and emphasize a detailed sequence analysis of the cohesin and
      dockerin domains. We also speculate about potential applications in nanoscience
      that may be based on cohesin-dockerin recognition.

PMID- 15260241
TI  - Hybrid peptide-polyketide natural products: biosynthesis and prospects towards
      engineering novel molecules.

PMID- 15260242
TI  - Characterization of protein structure and function at genome scale with a
      computational prediction pipeline.

PMID- 15260243
TI  - Spectral characterization of a color scanner by adaptive estimation.
AB  - A new method of spectral characterization for color scanners by the use of
      adaptive estimation is proposed. It deals with estimation of high-dimensional
      reflectance vectors from low-dimensional scanner response vectors when the
      scanner departs from linearity. We first investigate the spectral linearity of
      the scanner, and then estimate the spectral reflectance adaptively based on the
      local statistics of a set of neighboring training samples. As the proposed
      characterization method does not utilize the mathematically recovered spectral
      responsivity, its inherent inaccuracy is not critical to the spectral
      characterization. Experimental results showed significant advantage of adaptive
      estimation when compared with other methods.

PMID- 15260244
TI  - Statistics of the contrast of coherent images.
AB  - Contrast optimization, also known as image sharpening, is a method that can be
      used to estimate phase errors in coherent images. However, the contrast measure
      of a coherent image is a random variable because of the speckle present in
      coherent images. The variance of this measure puts a limit on the ability of
      contrast optimization to focus an image. We derive the probability distribution
      function of the most common contrast measure, the sum of the pixel intensities
      raised to a power. These statistics are then verified by a number of speckle
      simulations and compared with measured statistics from synthetic aperture sonar
      images. The developed statistics can be used as a tool to understand and improve
      the method of contrast optimization as well as assess its performance for a given
      imaging system. They can also be used to predict the effect of certain image
      processing operations on the contrast.

PMID- 15260245
TI  - Reference structure tomography.
AB  - Reference structure tomography (RST) uses multidimensional modulations to encode
      mappings between radiating objects and measurements. RST may be used to image
      source-density distributions, estimate source parameters, or classify sources.
      The RST paradigm permits scan-free multidimensional imaging, data-efficient and
      computation-efficient source analysis, and direct abstraction of physical
      features. We introduce the basic concepts of RST and illustrate the use of RST
      for multidimensional imaging based on a geometric radiation model.

PMID- 15260246
TI  - Clustered-minority-pixel error diffusion.
AB  - We present a clustered-minority-pixel error-diffusion halftoning algorithm for
      which the quantizer threshold is modified on the basis of the past output and a
      dot activation map. Dot area, dot shape, and dot distribution are more
      controllable than with other clustered-dot halftone algorithms such as Levien's
      algorithm. This method also effectively reduces structured mazelike artifacts in
      midtones that occur in Levien's algorithm. The dot distribution is further
      improved by using different error-diffusion weights for different input gray
      levels.

PMID- 15260247
TI  - Three-dimensional plasma field reconstruction with multiobjective optimization
      emission spectral tomography.
AB  - A novel emission spectral tomography algorithm based on multiobjective
      optimization is proposed. Its reconstruction results for asymmetrical emission
      coefficient fields are studied with computer simulation. The results show that
      this algorithm provides a significant improvement in reconstruction precision and
      convergence over traditional algorithms and is suitable for real-time
      reconstruction of an emission-coefficient field with incomplete data. In an
      experiment of the argon-arc plasma diagnosis, we adopted this algorithm and the
      spectrum relative-intensity method to obtain the three-dimensional distributions
      of temperature, ionization coefficient, and electron (ion) and atom densities.

PMID- 15260248
TI  - Phase imaging with a half-plane aperture.
AB  - A method that effects phase reconstruction from a single image of a phase object
      is presented. The method, which is founded on the iterative transform algorithm,
      more specifically the error reduction version of this algorithm, applies this
      algorithm in an unusual way, in that it attempts to solve the phase problem from
      the measurement of a single image of the object taken by using a half-plane
      aperture rather than its diffraction pattern. A description of the method, an
      analysis of its performance, and suggestions as to its potential application are
      given.

PMID- 15260249
TI  - Fractional finite Fourier transform.
AB  - We show that a fractional version of the finite Fourier transform may be defined
      by using prolate spheroidal wave functions of order zero. The transform is linear
      and additive in its index and asymptotically goes over to Namias's definition of
      the fractional Fourier transform. As a special case of this definition, it is
      shown that the finite Fourier transform may be inverted by using information over
      a finite range of frequencies in Fourier space, the inversion being sensitive to
      noise. Numerical illustrations for both forward (fractional) and inverse finite
      transforms are provided.

PMID- 15260250
TI  - Diffraction-based solid immersion lens.
AB  - A solid immersion lens based on diffraction (dSIL) is proposed as an alternative
      to the conventional design based on refraction. A design analogous to a Fresnel
      zone plate is derived in accordance with the Huygens-Fresnel principle.
      Fabrication of a binary dSIL is achieved by electron-beam lithography and
      reactive-ion etching on LaSF35, with index n = 2.014. Measurement of the point
      spread function is performed with near-field optical microscopy. The results are
      in accord with the expected resolution enhancement of a factor n with respect to
      the diffraction limit.

PMID- 15260251
TI  - Self-reconstruction property of fractional Bessel beams.
AB  - We study the self-reconstruction property of a fractional Bessel beam (FBB),
      where the FBB is described in terms of a Bessel beam of a fractional order for
      both amplitude and azimuthal phase components. The simulation and experimental
      results show that the FBB can overcome a block of obstacles and regenerate itself
      after a characteristic distance. As a comparison, the propagation of a Gaussian
      beam and an integer-order Bessel beam (IBB) through the same obstacles are also
      studied.

PMID- 15260252
TI  - Analysis and design of a concave diffraction grating with total-internal
      reflection facets by a hybrid diffraction method.
AB  - A novel hybrid diffraction method is introduced to simulate the diffraction and
      imaging of a planar-integrated concave grating that has total internal reflection
      (TIR) facets. The Kirchhoff-Huygens diffraction formula is adopted to simulate
      the propagation of the lightwave field in the free-propagation region, and a
      rigorous coupled-wave analysis is used to calculate the polarization-dependent
      diffraction by the grating. The hybrid diffraction method can be used to analyze
      accurately the imaging properties as well as the polarization-dependent
      diffraction characteristics of a concave grating. The dependence of several merit
      parameters of a concave grating with TIR facets on its basic geometric parameters
      is studied. Compared with one with metallic echelle facets, a concave grating
      with TIR facets shows a much lower polarization-dependent loss. Since more
      performance specifications can be considered in the design of a concave grating
      than with the conventional scalar method, design error can be reduced greatly
      with the present hybrid diffraction method.

PMID- 15260253
TI  - Synthesis of birefringent reflective gratings.
AB  - The layer-peeling method for reconstruction of fiber and waveguide gratings is
      extended to the case of birefringent reflective gratings with polarization
      dependent background index and polarization-dependent effective index contrast.
      Using a discrete grating model, we characterize the set of possible reflection
      and transmission Jones matrices and show that for a given wavelength, the total
      structure can be represented by a discrete reflector sandwiched between two
      retardation sections. In reflection the discrete reflector acts as a partial
      polarizer. A method for designing birefringent gratings is developed and tested
      numerically.

PMID- 15260254
TI  - Intrinsic speckle noise in off-axis particle holography.
AB  - In holographic imaging of particle fields, the interference among coherent wave
      fronts associated with particle scattering gives rise to intrinsic speckle noise,
      which sets a fundamental limit on the amount of information that particle
      holography can deliver. It has been established that the intrinsic speckle noise
      is especially severe in in-line holography because of superposition of virtual
      image waves, the direct transmitted wave, and the real image. However, at
      sufficiently high particle number densities, such as those typical in holographic
      particle image velocimetry (HPIV) applications, intrinsic speckle noise also
      arises in off-axis particle holography from self-interference among wave fronts
      that form the real image of particles. To overcome the latter problem we have
      constructed a mathematical model that relates the first- and second-order
      statistical properties of the intrinsic speckle noise to relevant holographic
      system parameters. Consistent with our experimental data, the model provides a
      direct estimate of the information capacity of particle holography. We show that
      the noise-limited information capacity can be expressed as the product of
      particle number density and the extent of the particle field along the optical
      axis. A large angular aperture of the hologram contributes directly to
      achievement of high information capacity. We also show that filtering in either
      digital or optical form is generally ineffective in removing the intrinsic
      speckle noise from the particle image as a result of the similar spectral
      properties of the two. These findings emphasize the importance of angular
      aperture in designing holographic particle imaging systems.

PMID- 15260255
TI  - Bhattacharyya distance as a contrast parameter for statistical processing of
      noisy optical images.
AB  - In many imaging applications, the measured optical images are perturbed by strong
      fluctuations or boise. This can be the case, for example, for coherent-active or
      low-flux imagery. In such cases, the noise is not Gaussian additive and the
      definition of a contrast parameter between two regions in the image is not always
      a straightforward task. We show that for noncorrelated noise, the Bhattacharyya
      distance can be an efficient candidate for contrast definition when one uses
      statistical algorithms for detection, location, or segmentation. We demonstrate
      with numerical simulations that different images with the same Bhattacharyya
      distance lead to equivalent values of the performance criterion for a large
      number of probability laws. The Bhattacharyya distance can thus be used to
      compare different noisy situations and to simplify the analysis and the
      specification of optical imaging systems.

PMID- 15260256
TI  - Modal power decomposition of beam intensity profiles into linearly polarized
      modes of multimode optical fibers.
AB  - We calculate the modal power distribution of a randomly and linearly polarized
      (LP) multimode beam inside a cylindrical fiber core from knowledge of spatial
      intensity profiles of a beam emitted from the fiber. We provide an exact analysis
      with rigorous proofs that forms the basis for our calculations. The beam from the
      fiber end is collimated by a spherical lens with a specific focal length. The
      original LP-mode basis is transformed by the spherical lens and forms another
      orthogonal basis that describes the free-space beam. By using this basis, we
      calculate the modal power distribution from the mutual-intensity profile. This is
      acquired by adopting a well-known mutual-intensity-profile-retrieving technique
      based on measurements of the intensity patterns several times after two
      orthogonal cylindrical lenses with varying separation. The feasibility of our
      decomposition algorithm is demonstrated with simulations.

PMID- 15260257
TI  - Second-order perturbation theory for scattering from heterogeneous rough
      surfaces.
AB  - We propose a model to calculate scattering from inhomogeneous three-dimensional,
      rough surfaces on top of a stratified medium. The roughness is made up of an
      ensemble of deposits with various shapes and permittivities whose heights remain
      small with respect to the wavelength of the incident light. This geometry is
      encountered in the remote sensing of soil surfaces, or in optics wherever there
      are contaminated planar components. Starting from a volume-integral equation
      involving the Green's tensor of the stratified medium, we derive a height
      perturbative expansion up to second-order. Our formulation, which depends
      explicitly on the profiles of each deposit and on the Fresnel coefficients of the
      layered substrate, accounts for double-scattering events and permits an
      evaluation of depolarization in the plane of incidence. Comparisons with rigorous
      calculations in the simplified case of two-dimensional geometries are presented.
      It is shown that the second-order scattering term can be much more important for
      heterogeneous surfaces than for their homogeneous counterparts.

PMID- 15260258
TI  - Optimal control law for classical and multiconjugate adaptive optics.
AB  - Classical adaptive optics (AO) is now a widespread technique for high-resolution
      imaging with astronomical ground-based telescopes. It generally uses simple and
      efficient control algorithms. Multiconjugate adaptive optics (MCAO) is a more
      recent and very promising technique that should extend the corrected field of
      view. This technique has not yet been experimentally validated, but simulations
      already show its high potential. The importance for MCAO of an optimal
      reconstruction using turbulence spatial statistics has already been demonstrated
      through open-loop simulations. We propose an optimal closed-loop control law that
      accounts for both spatial and temporal statistics. The prior information on the
      turbulence, as well as on the wave-front sensing noise, is expressed in a state
      space model. The optimal phase estimation is then given by a Kalman filter. The
      equations describing the system are given and the underlying assumptions
      explained. The control law is then derived. The gain brought by this approach is
      demonstrated through MCAO numerical simulations representative of astronomical
      observation on a 8-m-class telescope in the near infrared. We also discuss the
      application of this control approach to classical AO. Even in classical AO, the
      technique could be relevant especially for future extreme AO systems.

PMID- 15260259
TI  - On- and off-axis statistical behavior of adaptive-optics-corrected short-exposure
      Strehl ratio.
AB  - Statistical behavior of the adaptive-optics- (AO-) corrected short-exposure point
      spread function (PSF) is derived assuming a perfect correction of the phase's low
      spatial frequencies. Analytical expressions of the Strehl ratio (SR) fluctuations
      of on- and off-axis short-exposure PSFs are obtained. A theoretical expression of
      the short SR angular correlation is proposed and used to derive a definition of
      an anisoplanatic angle for AO-corrected images. Several applications of the
      analytical expressions are proposed: AO performance characterization,
      postprocessing imaging, light coupling into fiber, and exoplanet detection from a
      ground-based telescope.

PMID- 15260260
TI  - Correlation and structure functions of Hermite-sinusoidal-Gaussian laser beams in
      a turbulent atmosphere.
AB  - To study the performance of atmospheric optical links by using Hermite-sinusoidal
      Gaussian laset beam sources, we derive the log-amplitude and the phase
      correlation and structure functions of such beams in a turbulent atmosphere. Our
      formulations correctly reduce to the known higher-order mode correlation and
      structure functions, which in turn reduce to the fundamental-mode (TEM00-mode)
      results. Several special cases of our formulation are presented, among which the
      case involving Hermite-cosh-Gaussian dependence is especially noted, since this
      case is of interest to us owing to the nature of cosh dependence exhibiting the
      concentration of the energy in the outer lobes of the beam.

PMID- 15260261
TI  - Corneal surface reconstruction algorithm that uses Zernike polynomial
      representation.
AB  - We developed an algorithm that directly determines Zernike coefficients for the
      corneal anterior surface derived from the reflection image of a stimulus with
      pseudorandom encoding. This algorithm does not need to include calculation of
      corneal height maps. The numerical performance of the algorithm is good. It has
      the potential of determining corneal shape with submicrometer accuracy in
      obtaining Zernike coefficients. When applied to real eye measurements the
      accuracy of the procedure will be limited by the topographer that is used.

PMID- 15260262
TI  - Optimization of a laser satellite communication system with an optical
      preamplifier.
AB  - We derive a model that optimizes the performance of a laser satellite
      communication link with an optical preamplifier in the presence of random jitter
      in the transmitter-receiver line of sight. The system utilizes a transceiver
      containing a single telescope with a circulator. The telescope is used for both
      transmitting and receiving and thus reduces communication terminal dimensions and
      weight. The optimization model was derived under the assumption that the dominant
      noise source was amplifier spontaneous-emission noise. It is shown that, given
      the required bit-error rate (BER) and the rms random pointing jitter, an optimal
      transceiver gain exists that minimizes transmitted power. We investigate the
      effect of the amplifier spontaneous-emission noise on the optimal transmitted
      power and gain by performing an optimization procedure for various combinations
      of amplifier gain and noise figure. We demonstrate that the amplifier noise
      figure determines the optimal transmitted power needed to achieve the desired BER
      but does not affect the optimal transceiver telescope gain. Our numerical example
      shows that for a BER of 10(-9), doubling the amplifier noise figure results in an
      80% increase in minimal transmitted power for a rms pointing jitter of 0.44
      microrad.

PMID- 15260263
TI  - Degree of polarization as an objective method of estimating scattering.
AB  - A new method of determining objectively the amount of scattered light in an
      optical system has been developed. It is based on measuring the degree of
      polarization of the light in images formed after a double pass through the
      system. A dual apparatus composed of a modified double-pass imaging polarimeter
      and a wave-front sensor was used to measure polarization properties and
      aberrations of the system under test. We studied the accuracy of the procedure in
      a system that included a lanthanum-modified lead zirconate titanate (PLZT)
      ceramic plate able to generate variable amounts of scattered light as a function
      of the applied voltage. Changes in the voltage applied to the ceramics plate
      modified significantly the scattering contribution while hardly altering the wave
      front aberration. The degree of polarization was well correlated with the level
      of scattering in the system as determined by direct-intensity measurements at the
      tails of the double-pass images. This indicates that this polarimetric parameter
      provides accurate relative estimates of the amount of scattering generated in a
      system. The technique can be used in a number of applications, for example, to
      determine objectively the amount of scattered light in the human eye.

PMID- 15260264
TI  - Physically correct theoretical prism waveguide coupler model.
AB  - We develop new generalized four-wave-model-based waveguide mode equations for
      both isotropic and anisotropic systems by taking into account the influence of
      the incident light. These new mode equations eliminate the inherent deficiency in
      the conventional waveguide model, in which the action of incident light was
      neglected. Further, a peak-value-search (PVS) numerical method is developed to
      solve the four-wave-model-based mode equations. The PVS method has significant
      advantages in that accurate refractive index and thickness can be obtained
      without prior knowledge of the thickness of the air gap.

PMID- 15260265
TI  - Analysis of arbitrary defects in photonic crystals by use of the source-model
      technique.
AB  - A novel method derived from the source-model technique is presented to solve the
      problem of scattering of an electromagnetic plane wave by a two-dimensional
      photonic crystal slab that contains an arbitrary defect (perturbation). In this
      method, the electromagnetic fields in the perturbed problem are expressed in
      terms of the field due to the periodic currents obtained from a solution of the
      corresponding unperturbed problem plus the field due to yet-to-be-determined
      correction current sources placed in the vicinity of the perturbation.
      Appropriate error measures are suggested, and a few representative structures are
      presented and analyzed to demonstrate the versatility of the proposed method and
      to provide physical insight into waveguiding and defect coupling mechanisms
      typical of finite-thickness photonic crystal slabs.

PMID- 15260266
TI  - Modeling optical properties of liquid-crystal devices by numerical solution of
      time-harmonic Maxwell equations.
AB  - We consider numerical modeling of the optical properties of devices typical of
      beam-steering devices based on liquid-crystal materials: two-dimensional,
      anisotropic and inhomogeneous dielectric properties, periodic in one dimension. A
      mathematical formulation of the system of second-order partial differential
      equations for the components of the time-harmonic electric field is discretized
      by using a finite-element method based on curl-conforming edge elements. The
      discrete equations are also interpreted as equivalent finite-difference
      equations. It is shown how the resulting large sparse complex system of linear
      algebraic equations can be solved by an iterative method with convergence
      accelerated by a preconditioner based on fast Fourier transforms. Benchmarking
      results and the application to a realistic problem are reported. The practical
      limitations of the approach and its advantages and disadvantages compared with
      other approaches are discussed.

PMID- 15260267
TI  - Evanescent wave scattering and local electric field enhancement at ellipsoidal
      silver particles in the vicinity of a glass surface.
AB  - We report on the numerical analysis of the local electric field enhancement of
      nanosized silver ellipsoids placed in the evanescent field near a glass surface.
      Across the visible spectrum the enhancement factor for silver particles varies by
      more than one order of magnitude because of surface-plasmon resonance. Because of
      the spatially inhomogeneous excitation, higher-order modes additionally
      contribute and modify the spectral dependence of the electric field compared with
      plane-wave excitation. Moving the metal particle toward the glass surface
      increases the field enhancement and shifts the plasmon resonance, which in
      addition splits between both ends of the particle. Besides the near-field
      properties of such a probe we also discuss to what extent these local properties
      can be measured in the far field.

PMID- 15260268
TI  - Thermal antenna behavior for thin-film structures.
AB  - I show that under proper conditions, thin-film structures behave as thermal
      sources that are able to emit radiation in well-defined directions over a broad
      spectral band for both p- and s-polarization states of light. This effect results
      from the quantization of modes inside the structure as in a Fabry-Perot
      resonator. A theoretical demonstration of this effect is given by using the
      matrix transfer method. This result is similar to the most efficient reported
      results with gratings but with use of a completely different physical principle
      [Nature 416, 61 (2002)].

PMID- 15260269
TI  - Revisiting sputum smear microscopy.

PMID- 15260270
TI  - Should the 'bleach microscopy method' be recommended for improved case detection
      of tuberculosis? Literature review and key person analysis.
AB  - SETTING: It has been proposed that the sensitivity of direct sputum smear
      microscopy can be improved if sputum is liquefied with sodium hypochlorite (NaOCl
      or household bleach), and concentrated by centrifugation before acid-fast
      staining. OBJECTIVE: To summarise the results of the studies of the bleach method
      for improved sensitivity of sputum microscopy and to describe the opinions and
      knowledge of key persons in National Tuberculosis Control Programmes (NTPs) about
      this method. DESIGN: We searched Medline, EMBASE and Web of Science for studies
      comparing the bleach method to direct sputum smear microscopy in low- or middle
      income countries. Each study was assessed regarding methodology and field
      applicability. We also sent out questionnaires concerning the bleach method to
      key persons in NTPs in 85 countries. RESULTS: In 15 of the 19 studies identified
      there was a statistically significant improvement in the proportion of positive
      tests or sensitivity ranging from 7-253%. The majority (73%) of the key persons
      had heard of the bleach method. Forty-four per cent thought it could improve case
      detection in their countries, while 49% did not know; 93% of them would promote
      the bleach method; the most common reasons for doing so would be recommendations
      from the WHO or the IUATLD, or favourable studies performed in their own country.
      The bleach method was used routinely in only three countries. CONCLUSION: There
      is enough evidence to recommend the evaluation and introduction of the bleach
      method in most settings where mycobacterial culture is not performed routinely.

PMID- 15260271
TI  - Scanty AFB smears: what's in a name?
AB  - SETTING: A tuberculosis control project in Bangladesh. OBJECTIVE: To document the
      frequency and diagnostic value of smears with scanty acid-fast bacilli (AFB)
      (IUATLD/WHO scale, < 10/100 high power fields), and to assess the appropriateness
      of the current positivity threshold. DESIGN: Analysis of databases of laboratory
      registers, patient records and the diagnostic yield of sputum collection
      strategies. RESULTS: Scanty smears constituted about 10% of suspect and almost
      50% of follow-up smears. In suspect series, 10% of scanty 1-9/100 were not
      confirmed by another positive or scanty AFB sputum, compared to 7.5% of results
      at the current cut-off value of 10/100. Considering such results as positive by
      adopting a lower cut-off as low as the 1/100 used in the ATS scale added 1.5%
      false positives at the most. In return, the gain in confirmed positive cases was
      up to 10%, and that in positive results exceeded the incremental yield of the
      third diagnostic sputum. Significance of scanty follow-up smears at the end of
      the intensive phase was suggested by their association with treatment failure and
      unfavourable outcome overall. CONCLUSIONS: Scanty results (IUATLD/WHO scale) are
      not rare and should not be ignored. Adoption of a considerably lower positivity
      threshold would be appropriate in control programmes where basic conditions for
      reliable AFB microscopy, including regular quality assessment, are present.

PMID- 15260272
TI  - Smear examination of two specimens for diagnosis of pulmonary tuberculosis in
      Tiruvallur District, south India.
AB  - SETTINGS: A general hospital and three peripheral health institutions (PHI) in
      Tiruvallur District, south India. OBJECTIVE: To validate the case detection
      strategy for diagnosis of pulmonary tuberculosis by smear microscopy of two
      sputum specimens versus three. METHODS: In the Revised National Tuberculosis
      Control Programme (RNTCP), three smears from every symptomatic patient attending
      the PHI were examined for acid-fast bacilli (AFB) by Ziehl-Neelsen (ZN)
      microscopy. The data from the Tuberculosis Laboratory Registers from the above
      centres were analysed. RESULTS: Of 7843 chest symptomatics who had provided three
      sputum specimens for examination, 895 (11.4%) were smear-positive on at least two
      specimens. Examination of two specimens--first spot and early morning specimens
      (837, 93.5%) or early morning and second spot specimens (843, 94.2%)--yielded the
      highest number of cases. CONCLUSION: The examination of two sputum smears (one
      spot and an early morning) is as effective as examination of three smears.

PMID- 15260273
TI  - Long-term outcome in patients registered with tuberculosis in Zomba, Malawi:
      mortality at 7 years according to initial HIV status and type of TB.
AB  - SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of
      all adult patients who were registered for tuberculosis (TB) treatment 7 years
      previously according to initial human immunodeficiency virus (HIV) status and
      type of TB. DESIGN: A retrospective cohort study of adult patients registered for
      TB treatment between July and December 1995. Follow-up at patients' homes was
      performed at the end of treatment, at 32 months and at 84 months (7 years) from
      the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients
      were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV
      positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152
      (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100
      person-years of observation. HIV-positive patients had higher death rates than
      HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7
      2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6)
      and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than
      in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate
      in TB patients during and after anti-tuberculosis treatment. Adjunctive
      treatments to reduce death rates are urgently needed.

PMID- 15260274
TI  - Isolation of multidrug-resistant tuberculosis strains in patients from private
      and public health care facilities in Nairobi, Kenya.
AB  - SETTING: Health care facilities in Nairobi, Kenya. OBJECTIVE: To document the
      presence of multidrug-resistant tuberculosis (MDR-TB) strains in patients from
      Nairobi between September 1999 and October 2001. DESIGN: Descriptive study.
      RESULTS: Of the 983 referred patients who submitted sputum for culture and drug
      susceptibility testing (DST), 59% were males. Two hundred and nine (21.3%)
      patients had a positive culture, of whom 15.2% had a request for DST against
      isoniazid, rifampicin, streptomycin and ethambutol. Of these, 65 (43.6%) had an
      isolate resistant to one or more drugs, while 17 (11.4%) had MDR-TB. Ten (59.0%)
      cases were referred from public health care facilities while seven (41%) were
      from the private sector. Sixteen isolates were resistant to all four drugs. All
      MDR-TB cases but one were from Nairobi. CONCLUSION: The emergence of MDR-TB in
      Nairobi is a cause for concern. An outbreak would be catastrophic, creating not
      only increased morbidity and mortality but also a tremendous strain on already
      limited health care resources. Lack of policies for the treatment and management
      of MDR-TB and the unavailability of appropriate diagnostic facilities may
      increase its spread. Efforts to prevent outbreaks of MDR-TB should be emphasised.

PMID- 15260275
TI  - The value of counting BCG scars for interpretation of tuberculin skin tests in a
      tuberculosis hyperendemic shantytown, Peru.
AB  - SETTING: The tuberculin skin test (TST) is widely used as a diagnostic or
      screening test for Mycobacterium tuberculosis infection and disease. A peri-urban
      shantytown in the desert hills of south Lima, Peru, highly endemic for
      tuberculosis, and where bacille Calmette-Guerin (BCG) vaccine had been given in
      multiple doses until 1995. OBJECTIVE: To analyze the effect of multiple BCG
      vaccines on TST in a community-based setting. DESIGN: Point-prevalence survey of
      TST reactions of 572 people aged 6-26 years from 255 households. TST reactions
      were compared to the observed number of BCG scars and other potential risk
      factors (age, living with a TST-positive person, and contact with active
      tuberculosis). RESULT: People with two or more scars had significantly larger
      reactions, even after adjusting for potential risk factors. The adjusted
      population attributable fraction of being TST-positive and having two or more BCG
      scars was 26%. CONCLUSION: There is no demonstrated benefit of repeat BCG
      vaccination. We therefore recommend that physicians take into consideration the
      number of BCG scars when interpreting the TST and that programs give no more than
      one BCG vaccination.

PMID- 15260276
TI  - Implementation of the DOTS strategy in prisons at provincial level, Thailand.
AB  - SETTINGS: Sixteen prisons located in four geographic regions in Thailand.
      OBJECTIVES: To assess treatment outcomes of tuberculosis (TB) patients under the
      DOTS strategy in a prison programme. METHOD: The programme prospectively included
      1412 consecutive TB patients registered during Year 1 (June 1999-May 2000), Year
      2 (June 2000-May 2001) and Year 3 (June 2001-May 2002). DOTS implementation
      consisted of government commitment; passive detection by sputum smear microscopy;
      standardised short-course chemotherapy, including directly observed treatment by
      prison nurses; maintenance of drug stocks at provincial health offices; and a
      recording and reporting system. Data were collected using prison TB registers.
      RESULTS: The number of TB patients increased from 348 in Year 1 to 490 in Year 2
      and to 574 in Year 3. New smear-positive patients accounted for 82.0% of the
      total. Of the 1158 new smear-positive cases, 68.7% were cured, 17.6% died, 10.6%
      were transferred out, 2.6% failed, and 0.5% completed treatment. CONCLUSIONS:
      DOTS implementation in these prisons could not achieve the national target to
      cure 85% of new smear-positive cases. More interventions are needed to help
      reduce the deaths and transferred cases that mainly affected the treatment
      outcomes in these settings.

PMID- 15260277
TI  - Ongoing outbreak of tuberculosis in a low-incidence community: a molecular
      epidemiological evaluation.
AB  - SETTING: Federal State of Hamburg, Germany, 1997-2002. OBJECTIVE: To identify the
      pathways of tuberculosis (TB) transmission and to evaluate possible risk factors
      for recent transmission in Hamburg. DESIGN: A prospective, molecular
      epidemiological study was performed. Conventional contact tracing and an indepth
      epidemiological analysis were conducted. RESULTS: A predominant cluster of
      Mycobacterium tuberculosis strains was identified by IS6110 DNA fingerprinting of
      828 TB cases notified during the study period. The cluster expanded from seven
      cases in 1997 to 38 in June 2002. A single source case could not be identified.
      Transmission links were confirmed in 20 cases. Twenty-five patients were regular
      customers at a bar close to the red-light district. Seven patients, including one
      regular customer in the bar, were staying at a nearby hostel for homeless men,
      and four were living in a far-away hostel for alcoholic men. Of the 421 close
      contact persons investigated, 169 (40.1%) had positive tuberculin skin tests, and
      eight became ill (1.9%). Twelve of 20 cases with confirmed recent transmission
      could only be determined a posteriori by fingerprinting. CONCLUSIONS: An ongoing
      outbreak at a local bar indicates chronic alcoholism as a high-risk factor for
      the dissemination of TB in a large metropolitan area. The fact that conventional
      contact tracing is insufficient for the detection of chains of transmission in
      this milieu indicates the need for an improved, location-based approach, e.g.,
      the implementation of an outreach strategy.

PMID- 15260278
TI  - Consecutive-dose pharmacokinetics of rifapentine in patients diagnosed with
      pulmonary tuberculosis.
AB  - OBJECTIVE: To characterise the pharmacokinetics of two consecutive doses of
      rifapentine (RPT) in patients diagnosed with pulmonary tuberculosis at a South
      African hospital. DESIGN: Forty-five patients received RPT doses of 600, 750 and
      900 mg, based on body weight, after receiving a soup-based meal. Doses were
      administered to each subject on study days 1 and 5. All patients had already
      received not less than 4 weeks and not more than 6 weeks of standard
      antimycobacterial therapy (including isoniazid, rifampicin, pyrazinamide and
      ethambutol). Serial blood samples were collected between 0 and 72 h post-dose.
      RPT and 25-desacetyl-RPT concentrations were determined using validated high
      performance liquid chromatography methods. The plasma concentration-time data
      were analysed using a noncompartmental approach and compared to healthy volunteer
      data from a previous study. RESULTS: Median peak plasma concentrations for RPT in
      the patient cohort were 15.19 and 15.48 microg/ml on study days 1 and 5,
      respectively. Time to reach these concentrations was 5.00 and 5.08 h and plasma
      elimination half-lives were 11.63 and 12.03 h, respectively. Areas under the
      plasma concentration-time curve (0-72 h) were 355.81 and 371.89 microg x h/ml on
      the two occasions, respectively. CONCLUSION: A 15 mg/kg dose of RPT was well
      absorbed and well tolerated. The variability observed between individuals and
      between occasions was small, and similar to that seen in data from previous
      studies in healthy volunteers.

PMID- 15260279
TI  - Contact investigation for cases of pulmonary Mycobacterium bovis.
AB  - SETTING: A local tuberculosis control program in San Diego County, California.
      OBJECTIVE: To determine the yield of contact investigations of pulmonary
      Mycobacterium bovis cases. DESIGN: Retrospective review of medical records
      comparing tuberculin skin test (TST) conversion rates found in contact
      investigations of pulmonary M. bovis cases to conversion rates found in contact
      investigations of pulmonary M. tuberculosis cases. RESULTS: For the years 1994
      2001, we identified 77 contacts of pulmonary M. bovis cases and 469 contacts of
      M. tuberculosis cases that met the study criteria. TST conversion rates were not
      significantly different based on species of the source case (13% for M. bovis,
      15% for M. tuberculosis, P = 0.20). This finding was also observed when the
      results were stratified by presence of a cavity on chest X-ray, history of cough
      at diagnosis and human immunodeficiency virus (HIV) status of the source case.
      CONCLUSION: These results suggest that contact investigations for pulmonary M.
      bovis cases should be conducted in the same manner as those conducted for
      pulmonary M. tuberculosis cases.

PMID- 15260280
TI  - Can we improve the management of chronic obstructive respiratory disease? The
      example of asthma in adults.
AB  - SETTING: Zeralda health district, Algeria. OBJECTIVE: To analyse the impact of
      asthma refresher courses on the knowledge, attitudes and practice of general
      practitioners (GPs) working in primary health centres (PHC); to improve the
      system of referral between the PHCs and the district reference centre; and to
      measure the impact of the intervention on the management of asthma patients.
      METHODS: Before and after study: situation analysis with an epidemiological
      survey in the general population and a study of the demand for care in three PHCs
      and an emergency department, three refresher training workshops for voluntary GPs
      and adoption of new consensual methods of collaboration. RESULTS: Despite a
      district asthma prevalence of 1.6%, patients were usually seen in emergency
      situations and sent to the district reference centre for follow-up. The refresher
      courses were attended by 56 GPs. Apart from improvements in knowledge, their
      practices and prescribing habits changed, with more beta-agonists (68.5% after
      vs. 12% before) and inhaled anti-inflammatories (52% vs. 0%), and less
      theophylline (2% vs. 55%), antibiotics (13% vs. 59%) and mucolytics (9% vs.
      73.5%). The referral system was improved as follows: 69 health personnel were
      trained by GPs, recording and reporting forms designed during the workshops were
      implemented, essential emergency drugs were identified and collaboration between
      GPs and specialists at the reference centre was enhanced.

PMID- 15260281
TI  - Prevalence and characteristics of narghile smoking among university students in
      Syria.
AB  - SETTING: Narghile (waterpipe) smoking is increasing in all Arab societies, but
      little is known about its pattern of use. METHODS: In 2003, a cross-sectional
      survey was conducted among students at Aleppo University using an interviewer
      administered questionnaire. A representative sample of 587 students participated
      (278 males, 309 females; mean age 21.8 +/- 2.1 years; response rate 98.8%).
      RESULTS: Ever narghile smoking was seen among 62.6% of men and 29.8% of women,
      while current smoking was seen among 25.5% of men and 4.9% of women. Only 7.0% of
      the men used narghile daily. Age of initiation was 19.2 +/- 2.2 and 21.7 +/- 3.2
      years for men and women, respectively (P < 0.001). The salient feature of
      narghile smoking was its social pattern, where most users initiated and currently
      smoked narghile with friends. Narghile and cigarette smoking were related among
      students, with narghile smoking most prevalent among daily cigarette smokers.
      Multivariate correlates of narghile smoking were being older, male, originating
      from the city, smoking cigarettes, having friends who smoke narghile, and coming
      from a household where a greater number of narghiles were smoked daily.
      CONCLUSIONS: Narghile smoking is prevalent among university students in Syria,
      where it is mainly practiced by men, intermittently, and in the context of social
      activities with friends.

PMID- 15260282
TI  - Lymphoepithelioma-like carcinoma of the lung: experience with ten cases.
AB  - OBJECTIVE: Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare form of
      non-small cell lung cancer predominantly affecting young non-smoking Asians, and
      there has been only limited experience in its palliative chemotherapy and
      radiotherapy. We investigated tumour response, time to progression and survival
      of LELC patients who received such treatment. DESIGN: We prospectively recruited
      patients with confirmed advanced LELC who were treated with chemoradiotherapy in
      our unit, a regional tertiary referral centre for lung cancer treatment. RESULTS:
      There were 10 patients (five males, age 47 +/- 9.8 years, median follow-up 22
      months) with advanced LELC (respectively 1, 4, and 5 patients at TNM stage IIIA,
      IIIB and IV) who received systemic chemotherapy and radiotherapy. The primary
      chemotherapy regimen consisted of 5-fluorouracil/leucovorin/cisplatin. The
      response rates to 5-fluorouracil/leucovorin/cisplatin were 60% partial response,
      10% stable disease, and 30% progressive disease. Eight patients were also given
      local radiotherapy. Five patients received salvage chemotherapy when disease
      progressed after primary chemotherapy. The overall median survival was 23.4 +/-
      4.7 months. CONCLUSION: The encouraging response to combination chemotherapy with
      5-fluorouracil/leucovorin/ cisplatin, although empirical, supports its use with
      radiotherapy in unresectable lymphoepithelioma-like carcinoma of the lung.

PMID- 15260283
TI  - Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful
      tool.
AB  - Diagnosis of tuberculosis is challenging, especially in human immunodeficiency
      virus (HIV) positive persons who may have atypical clinical and radiographic
      features. We report the isolation of Mycobacterium tuberculosis from sputum
      samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest
      radiographs and negative sputum smears for acid-fast bacilli. Six of them had
      strongly positive tuberculin reactions while four were severely immunosuppressed.
      Our observation highlights the utility of routine sputum culture in the diagnosis
      of tuberculosis in high-risk individuals.

PMID- 15260284
TI  - Rapid diagnosis of pulmonary tuberculosis by mycobacteriophage assay.
AB  - We evaluated FASTPlaqueTB, a recently introduced bacteriophage assay for rapid
      detection of Mycobacterium tuberculosis complex in sputum specimens, using 169
      non-duplicate sputum specimens from patients suspected of pulmonary tuberculosis.
      The results of 160 specimens were analysed. FASTPlaqueTB assay detected
      tuberculosis in 77% (46/60) of culture-positive cases. Among the AFB smear
      positive cases (n = 47) it had a sensitivity of 76% and specificity of 60% while
      among AFB smear-negative cases (n = 113) its sensitivity and specificity were 78%
      and 98%, respectively. The overall sensitivity and specificity of the technique
      were 77% and 96%, respectively, and the positive and negative predictive values
      were respectively 92% and 87%. The overall efficiency of the test was 89%. Test
      results were available in 48 h.

PMID- 15260285
TI  - Mycobacterium bovis tuberculosis: from animal to man and back.
AB  - Rare cases of tuberculosis due to Mycobacterium bovis have been described in
      humans who have been exposed to cattle or other infected animals. We report a
      case of tuberculosis in cattle exposed to a patient infected with M. bovis, where
      the strain isolated in the cattle and the patient were identical. As the patient
      is reported to have been exposed and contaminated during childhood, this seems to
      be the first documented case of transmission of M. bovis from animal to man and
      back to animal.

PMID- 15260286
TI  - Successful treatment of multidrug-resistant tuberculosis following drug-induced
      hepatic necrosis requiring liver transplant.
AB  - A 28-year-old female developed multidrug-resistant (MDR) tuberculous
      lymphadenitis following a trip to India. She was initially treated with a four
      drug regimen of first-line anti-tuberculosis medications, but when sensitivities
      indicated resistance to isoniazid and rifampin, her regimen was altered to
      ciprofloxacin (CFX), pyrazinamide (PZA) and ethambutol. She subsequently
      developed a rash, flu-like symptoms and fever, which progressed to acute hepatic
      necrosis despite discontinuation of medication. The clinical presentation and
      subsequent investigations suggested a hypersensitivity reaction, possibly related
      to the quinolone. The patient subsequently had an orthoptic liver transplant;
      second-line anti-tuberculosis medications were restarted to which she responded
      clinically and radiologically. Our findings raise the possibility that the CFX
      and PZA combination was responsible for the hepatic necrosis. The patient also
      illustrates that active, even MDR tuberculosis is not a contraindication to
      hepatic transplant.

PMID- 15260287
TI  - Capacity building for research: report on a UNION Strategic Planning Workshop.
      Report of a workshop held during the International Union Against Tuberculosis and
      Lung Disease World Conference on Lung Health, Montreal, Canada, 7 October 2002.
AB  - The International Union Against Tuberculosis and Lung Disease (UNION) has a
      decade of experience in conducting short courses on research methods for the
      promotion of lung health. In a parallel initiative, the UNION has collaborated
      with the American Thoracic Society (ATS) to develop courses on international
      respiratory epidemiology that have been expanded by the ATS throughout Latin
      America. The two initiatives have similar aims, and the courses offered by the
      two organisations have intentionally been similar in terms of focus and
      complementary in regions targeted. The target regions of the UNION, drawing on
      several decades of experience in offering short courses on tuberculosis, have
      been Africa, the Black Sea Rim, the Middle East and Asia, while the target
      regions of the ATS have been Central and South America. This workshop aimed first
      to provide an opportunity for those who have taught on the courses and those who
      have participated to share their experiences and learn from them, and second to
      provide a basis on which to develop a strategic plan for future courses. This
      report summarises the contributions of the workshop participants and the
      conclusions reached.

PMID- 15260288
TI  - Research methods for promotion of lung health.
AB  - The goal of health research is to develop new knowledge for action to improve
      health. Relevant health research includes study of diseases, their causes and
      their treatment/prevention as well as structure and utilisation of health
      services and policies to improve lung health. As resources are not infinite,
      priorities must be established. These are determined by the relative frequency of
      a condition, how much dysfunction or disability it produces and whether there are
      cost-effective means to deal with it. Epidemiology is the discipline used to
      address these issues. Using it, one can describe the distribution and relative
      importance of a condition (the descriptive study), identify determinants and
      define its natural history (the analytical study), assess methods of prevention,
      cure and amelioration (the experimental study) and evaluate the process and
      outcome of services (health services or operational research). Epidemiology
      addresses itself to determining causation among associated variables.
      Characteristics associated with causation include consistency, strength of
      association, specificity, dose response, temporal relationship, coherence, and
      experimental evidence. Epidemiology can truly be described as the 'basic science
      of public health.' When used strategically, it can create the new knowledge that
      is the cornerstone for improving the health of the whole population.

PMID- 15260289
TI  - EQA for AFB smear microscopy manual.

PMID- 15260290
TI  - Bound and unextractable pesticidal plant residues: chemical characterization and
      consumer exposure.
AB  - Plants are well known to incorporate pesticides into bound and unextractable
      residues that resist solubilization in common laboratory solvents and are
      therefore not accessible to standard residue analysis. A characterization of such
      residues has been proposed for incorporation rates above trigger values of 0.05
      mg kg(-1) parent pesticide equivalents, or percentage values of 10% (United
      States Environmental Protection Agency, 1995) or 25% (Commission of the European
      Communities, 1997) of the total radioactive residue. These trigger values are
      often exceeded. The present review describes the current status of the chemical
      characterization and animal bioavailability of bound and unextractable residues
      that may be xenobiotic in nature or result from natural recycling of simple
      degradation products. The latter case represents a mechanism of detoxification.
      Bound residues have been shown to be covalent or non-covalent in nature. With
      regard to the plant matrix molecules involved, incorporation into proteins,
      lignins, pectins, hemicelluloses and cutins has been demonstrated, and four
      covalent linkage types are known. Animal feeding experiments have revealed cases
      of low as well as high bioavailability. Many of the studies are limited by
      experimental uncertainties and by results only being reported as relative
      percentage values rather than absolute exposure. A preliminary value of absolute
      exposure from bound and unextractable residues is derived here for the first time
      from eight case studies. The mean exposure (ca 1.5 mg kg(-1) pesticidal
      equivalents) exceeds some of the existing maximum residue levels (MRLs) of
      residual free pesticides that are typically in the range of 0.05-1 mg kg(-1). A
      mathematical framework for the correction of current maximum residue levels is
      presented for cases of highly bioavailable bound residues. As bound pesticidal
      residues in food plants could represent a source of significant consumer
      exposure, an experimental test scheme is proposed here. It consists of basic
      chemical characterization, model digestibility tests and, in exceptional cases,
      animal bioavailability and additional toxicological studies.

PMID- 15260291
TI  - Zanthoxylum piperitum (DC), a potential feeding deterrent for mammals: studies
      with Microtus ochrogaster (Wagner).
AB  - Total extract from the fruit of Szechuan pepper (Zanthoxylum piperitum DC), the
      volatile components of the extract and a non-volatile fraction containing
      alkylamides (NVA fraction) are feeding deterrents for rats. The present study
      investigated the effectiveness of these natural repellents in prairie voles
      (Microtus ochrogaster Wagner). Two-choice feeding trials were conducted during
      which food-deprived voles were offered choices between oat-bran wafers. In
      Experiment 1, 10 voles were given three sets of feeding trials, each 2 h long.
      Baseline consumption was established during the first set of two trials by
      offering a choice between two oat-bran wafers dipped in ethanol, the control
      solvent. During the second set of two trials the voles were given a choice
      between an oat-bran wafer dipped in ethanol and a wafer dipped in Zanthoxylum
      extract. During the third set the voles were given a choice between a wafer
      served on top of a screened dish containing a sample of ethanol and a wafer
      served on top of a dish containing a sample of extract. In this manner the voles
      were exposed to volatile compounds emanating from the extract but could not
      contact it. Wafers dipped in extract were almost completely avoided. The volatile
      components of extract also significantly reduced food intake. In Experiment 2,
      habituation to the volatile constituents of extract was examined in 16
      Zanthoxylum-naive voles. Baseline consumption was established by offering two
      wafers served on top of screened dishes containing ethanol. This was followed by
      twelve tests during which a choice between a wafer served above a sample of
      ethanol and a wafer served above a sample of extract was given. The voles failed
      to habituate to the volatile components of extract, consistently consuming less
      of the wafers served above extract. In Experiment 3 a dose-response curve to
      Zanthoxylum extract was established, using 12 stimulus-naive voles. After
      baseline consumption was established, the animals were given two tests each,
      presenting a choice between a control wafer and a wafer dipped in a dilution of
      extract (0.001-100 g liter(-1)). Only concentrations of 10 and 100 g liter(-1)
      reduced food intake. In Experiment 4 the effects of the non-volatile fraction of
      extract were compared to those of whole extract. Vegetable oil was used as
      solvent. Eight stimulus-naive voles were given two tests with a choice between an
      oil-dipped and an extract-dipped wafer. A second group of eight voles received
      two tests with a choice between an oil-dipped and NVA-dipped wafer. Extract
      dipped wafers were avoided, but the NVA fraction had no effect on food
      consumption.

PMID- 15260292
TI  - Comparative activity of Choristoneura fumiferana nucleopolyhedrovirus propagated
      in different hosts.
AB  - The biological activity of the Ireland strain of Choristoneura fumiferana (Clem)
      nucleopolyhedrovirus (CfMNPV) propagated in different hosts was determined to
      provide the basis upon which genetically modified CfMNPV, or other naturally
      occurring isolates, should be compared. Occlusion bodies (OB) derived from CF-203
      cells were significantly larger and more pathogenic than those propagated in vivo
      when tested against the fifth larval instar of C fumiferana (Clem) and C
      occidentalis Freeman. The dose-responses (LD50 and LD95, expressed as occlusion
      bodies per larva) of C fumiferana larvae to in vitro-propagated OBs were 274 and
      5785, respectively. The values of LD50 and LD95 to C occidentalis larvae were 19
      and 118, respectively. There were no significant differences in pathogenicity or
      size when OBs propagated in C fumiferana larvae were tested against either insect
      species, nor were there significant differences for OBs propagated in C
      occidentalis larvae. The LD50 and LD95 of in vivo-produced OBs to C fumiferana
      were 925 and 61988, respectively. The LD50 and LD95 to C occidentalis were 50 and
      453, respectively. OBs propagated in vitro had a mean volume of 13.13 microm3,
      whereas those propagated in vivo ranged from 0.84 to 1.41 microm3. The median
      survival time-responses (ST50) of fifth-instar C fumiferana or C occidentalis
      larvae to OBs propagated in vivo were not significantly different from those
      propagated in vitro at the dosage levels tested. Values of ST50 of C fumiferana
      larvae to in vitro- and in vivo-produced OBs at dosages causing less than 50%
      mortality rangedfrom 9.6 to 9.8 days post-inoculation (dpi), whereas a LD95 dose
      resulted in ST50 values ranging from 7.3 to 7.7 days. ST50 values of C
      occidentalis larvae at dosages causing less than 50% mortality ranged from 9.8 to
      10.2 dpi, whereas a LD95 dose resulted in ST50 values ranging from 9.5 to 9.8
      dpi. The median feeding cessation time-response (FT50) of fifth-instar C
      fumiferana larvae to OBs propagated in vitro (5.7 days) was not significantly
      different from the FT50 of those propagated in vivo in either insect species (5.3
      and 5.7 days) at the dosage level tested (LD95). No significant differences in
      FT50 values were observed between OBs propagated in either larval host. The FT50
      of C occidentalis larvae to OBs propagated in vitro (7.7 days) was not
      significantly different from that to those propagated in vivo in C occidentalis
      larvae (7.6days), but somewhat different (7.2 days) from that to those propagated
      in C fumiferana larvae. Results indicate that CfMNPV can be propagated in vivo in
      either C fumiferana or C occidentalis larvae (or sequentially through both)
      without alteration in infectivity, although the use of the CF-203 cell line
      yields the most biologically active OBs.

PMID- 15260293
TI  - Toxicity of the entomopathogenic fungus, Metarhizium anisopliae (Deuteromycotina:
      Hyphomycetes) to adult females of the blowfly Lucilia sericata (Diptera:
      Calliphoridae).
AB  - The fungus Metarhizium anisopliae (Metchnikoff) (Deuteromycotina: Hyphomycetes)
      is a natural component of soil flora world-wide and is a causal agent of the
      green muscardine diseases of insects. The use of this pathogen as a potential
      biocontrol agent against adult females of the blowfly, Lucilia sericata (Meigen)
      (Diptera: Calliphoridae) was considered. The blowfly L sericata is an
      economically important agent of cutaneous myiasis of sheep, particularly in
      northern Europe. Exposure of flies to suspensions of fungal spores by immersion,
      topical application or tarsal contact with treated surfaces all resulted in high
      levels of fatal infection. Spores suspended in silicone oil resulted in higher
      levels of infection (50-70%) than those formulated in a 0.3 glitre(-1) solution
      of the detergent Tween 80 (10-20%). Spore concentration had a significant effect
      on levels of infection of flies, with the highest levels of mortality (64%)
      resulting from a suspension of 1 x 10(7) conidia ml(-1). The duration of tarsal
      contact had a significant effect on levels of infection. Mean infection levels of
      30% were observed following exposure of free-flying adults to a single spore
      treated, 5 x 15 cm2 cloth surface suspended from the roof of a cage (30 cm cube).
      The implications of the results for the potential use of M anisopliae in the
      biocontrol of blowflies are discussed.

PMID- 15260294
TI  - Degradation and leaching potential of pesticides in biobed systems.
AB  - Biobeds provide a potential solution to pesticide contamination of surface waters
      arising from the farmyard. Previous work has shown that biobeds can effectively
      treat spills and splashes of pesticide. This study investigated the potential for
      biobeds to treat much larger volumes and amounts of pesticide waste not only
      arising from spills but also from washing processes. Two systems were assessed
      using a range of pesticides at the semi-field scale, ie a lined biobed system and
      an unlined system. Studies using the lined biobeds demonstrated that water
      management was crucial, with biobeds needing to be covered to exclude rain-water.
      Once covered, the top of the biobed became hydrophobic, restricting moisture loss
      and resulting in saturated conditions at depth. The drying out of the top layer
      coincided with a measured decrease in microbial biomass in the treated biobeds.
      Applied pesticides were effectively retained within the 0-5 cm layer. Whilst all
      pesticides tested degraded, low moisture content and microbial activity meant
      degradation rates were low. Studies using unlined biobeds showed that only the
      most mobile pesticides leached, and for these > 99% was removed by the system,
      with a significant proportion degraded within 9 months. Peak concentrations of
      the two most mobile pesticides did however exceeded the limits that are likely to
      be required by regulatory bodies. However, it is thought that these limits could
      be reached by optimisation of the system.

PMID- 15260295
TI  - Predicting mortality of phosphine-resistant adults of Sitophilus oryzae (L)
      (Coleoptera: Curculionidae) in relation to changing phosphine concentration.
AB  - Adults of a phosphine-resistant strain of Sitophilus oryzae (L) were exposed to
      constant phosphine concentrations of 0.0035-0.9mg litre(-1) for periods of
      between 20 and 168h at 25 degrees C, and the effects of time and concentration on
      mortality were quantified. Adults were also exposed to a series of treatments
      lasting 48, 72 or 168 h at 25 degrees C, during which the concentration of
      phosphine was varied. The aim of this study was to determine whether equations
      from experiments using constant concentrations could be used to predict the
      efficacy of changing phosphine concentrations against adults of S oryzae. A
      probit plane without interaction, in which the logarithms of time (t) and
      concentration (C) were variables, described the effects of concentration and time
      on mortality in experiments with constant concentrations. A derived equation of
      the form C(n)t = k gave excellent predictions of toxicity when applied to data
      from changing concentration experiments. The results suggest that for resistant S
      oryzae adults there is nothing inherently different between constant and changing
      concentration regimes, and that data collected from fixed concentrations can be
      used to develop equations for predicting mortality in fumigations in which
      phosphine concentration changes. This approach could simplify the prediction of
      efficacy of typical fumigations in which concentrations tend to rise and then
      fall over a period of days.

PMID- 15260296
TI  - Impact of sub-lethal residues of azinphos-methyl on the pheromone-communication
      systems of insecticide-susceptible and insecticide-resistant obliquebanded
      leafrollers Choristoneura rosaceana (Lepidoptera: Tortricidae).
AB  - The effects of sub-lethal residues of azinphos-methyl on pheromone production,
      calling, female attractiveness and the ability of males to locate sources of
      natural and synthetic pheromone were compared in azinphos-methyl-susceptible
      (susceptible) and azinphos-methyl-resistant (resistant) obliquebanded
      leafrollers, Choristoneura rosaceana (Harris). The amount of pheromone in
      susceptible females was reduced by 29-33% after exposure to azinphos-methyl; this
      treatment did not affect the pheromone content of resistant females. Azinphos
      methyl-treated resistant females contained 39-43% less pheromone than azinphos
      methyl-treated susceptible females. Resistant females that were not treated with
      azinphos-methyl contained 35-56% less pheromone than susceptible females that
      were not treated with insecticide. The incidence of calling was reduced by 67
      100% in azinphos-methyl-treated susceptible females; the incidence of calling by
      resistant females was not affected by exposure to azinphos-methyl. The incidence
      of calling by azinphos-methyl-treated susceptible females was 58-100% lower than
      that of azinphos-methyl-treated resistant females. There was no difference in the
      incidence of calling between susceptible and resistant females that had not been
      treated with insecticide. In a flight tunnel, treatment with insecticide reduced
      the attractiveness of susceptible females by 38%; treatment with insecticide did
      not affect the attractiveness of resistant females. There was no difference in
      the proportion of males attracted to susceptible and resistant females that had,
      or had not been treated with insecticide. In an apple orchard, the attractiveness
      of susceptible and resistant females treated with azinphos-methyl was reduced by
      84 and 12%, respectively. The proportion of males attracted to azinphos-methyl
      treated susceptible females was 58% lower than the proportion attracted to
      azinphos-methyl-treated resistant females, whereas, if females were not treated
      with insecticide, the proportion attracted to resistant females was 57% lower
      than the proportion attracted to susceptible females. In a flight tunnel,
      azinphos-methyl did not affect the ability of susceptible or resistant males to
      locate a source of pheromone gland extract. Likewise, in an apple orchard, the
      insecticide treatment had no effect on the ability of susceptible or resistant
      males to locate a source of synthetic pheromone. In a flight tunnel, there was no
      difference in the proportion of azinphos-methyl-treated susceptible and resistant
      males locating a source of pheromone gland extract; however, in the orchard, 39%
      fewer azinphos-methyl-treated resistant males located a source of synthetic
      pheromone than azinphos-methyl-treated susceptible males. A similar proportion of
      susceptible and resistant males that had not been treated with insecticide
      located a source of pheromone gland extract in the flight tunnel, but in the
      orchard, the proportion of resistant males not treated with azinphos-methyl that
      located the source of synthetic pheromone was 32% lower than the proportion of
      susceptible males not treated with this insecticide. The implications of the
      differences in the effect of sub-lethal residues of azinphos-methyl on the
      pheromone communication system of susceptible and resistant moths are discussed
      in relation to the theory of the development of insecticide resistance, the
      detection of resistance in feral populations of moths using sex pheromone-baited
      traps, and the control of moths using sex pheromone-mediated mating disruption.

PMID- 15260297
TI  - Reversal of the inhibition of photosynthesis by herbicides affecting
      hydroxyphenylpyruvate dioxygenase by plastoquinone and tocopheryl derivatives in
      Chlamydomonas reinhardtii.
AB  - Isoxaflutole or pyrazolate inhibition of tocopherol and plastoquinone
      biosynthesis in the green alga Chlamydomonas reinhardtii Dang leads to the
      inactivation of photosystem II and the degradation of its reaction centre D1
      protein when exposed to strong light. Cell-permeable short-chain derivatives of
      plastoquinone and tocopherol were tested in the reversal. Addition of decyl
      plastoquinone reverses herbicide-induced inhibition of photosynthesis and
      inactivation of photosystem II in short-time (1 h) exposure of the algae to high
      light. In high light longer than 1 h, decyl-plastoquinone alone loses
      effectiveness, but a synthetic permeable tocopheryl derivative retards the
      inhibitory effects on photosystem II and on the degradation of the D1 protein.
      This indicates that tocopherol deficiency induced by the herbicides makes a major
      contribution to their secondary mode of action in high light stress.

PMID- 15260298
TI  - Determination of aldicarb, carbofuran and some of their main metabolites in
      groundwater by application of micellar electrokinetic capillary chromatography
      with diode-array detection and solid-phase extraction.
AB  - This paper describes a UV detection method for the pesticides aldicarb and
      carbofuran, and some of their main metabolites, aldicarb-sulfoxide, aldicarb
      sulfone and 3-hydroxy-carbofuran, in ground waters. Micellar electrokinetic
      chromatography (MEKC) with diode-array detection was developed for their
      determination at 210 nm. The experimental study was performed using sodium
      dodecyl sulfate (SDS) at a concentration level of 140 mM, and a buffer of
      borax/HCl 20 mM at pH 8 which gives the best resolution with an analysis time of
      less than 20 min. Different instrumental parameters such as voltage (23 kV),
      injection time (12 s) and temperature (25 degrees C) were optimized. The
      detection limits were in the range 2-7.4 microg glitre(-1) by solid-phase
      extraction (SPE) with a subsequent evaporation step. Groundwater spiked samples
      were pre-concentrated off-line with graphite carbon and subsequently analyzed by
      MEKC with diode-array detection yielding average recoveries between 77 and 97% (n
      = 4) with RSD between 2-7%.

PMID- 15260299
TI  - Changes in susceptibility to conventional insecticides of a Cry1Ac-selected
      population of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae).
AB  - The changes in the susceptibility of the cotton bollworm, Helicoverpa armigera
      (Hubner) to three insecticides (lambda-cyhalothrin, phoxim and endosulfan)
      commonly used for control of this pest in China were monitored by bioassays at
      various generations. The insects were originally collected from Bt cotton fields
      and selected with Cry1Ac over 44 generations. In comparison with a susceptible
      strain, the larval resistance of the Bt-selected populations to Cry1Ac toxin
      increased 106-fold. Simultaneously, the resistance levels to lambda-cyhalothrin,
      phoxim and endosulfan declined dramatically. The results indicated no positive
      cross-resistance between Cry1Ac toxin and the insecticides. Evidence of the lack
      of cross-resistance to three commonly used synthetic insecticides in our
      laboratory-derived Cry1Ac-resistant population may suggest that growers can
      confidently use these insecticides if and when resistance to Cry1Ac cotton does
      occur.

PMID- 15260300
TI  - Development of biodegradable aluminium carboxymethylcellulose matrices for
      mosquito larvicides.
AB  - The use of ecofriendly biodegradable controlled-release formulations of mosquito
      larvicides could reduce the frequency of application and losses due to
      degradation of the insecticide compared with conventional formulations. Among the
      20 matrices developed by entrapping the organophosphorus mosquito larvicide,
      fenthion, in carboxymethylcellulose ionotropically cross-linked with aluminium
      ions which were studied for release profiles, two matrices, CRF3b and CRF5b, were
      found to be stable for 16 and 14 weeks under simulated field conditions. The
      average concentration of fenthion released per week ranged from 0.06 to 3.5 mg
      litre(-1) for CRF3b and 0.09 to 2.72 mg litre(-1) for CRF5b. Of these two
      formulations, CRF3b was the more stable, maintaining the concentration of the
      active ingredient at the level required to effect mosquito control. The
      cumulative release of fenthion per pellet was 80% from CRF3b and 72% from CRF5b.
      Based on the study with fenthion, two similar matrices for triflumuron, a
      benzoylphenylurea insect growth regulator, STAR3b and STAR5b were developed.
      These matrices were stable up to 16 weeks with the average concentration of
      triflumuron released per week ranging from 0.05 to 3.44 mg litre(-1) for STAR3b
      and 0.07 to 2.71 mg litre(-1) for STARSb. The cumulative release of triflumuron
      per pellet was 75% from STAR3b and 76% from STAR5b. From the results of this
      study under simulated conditions, it is estimated that the application of four
      pellets of either fenthion or triflumuron per square metre of the breeding
      surface may play a useful role in controlling Culex quinquefasciatus Say in
      larval habitats for about 4 months.

PMID- 15260301
TI  - Distribution and metabolism of D/L-, L- and D-glufosinate in transgenic,
      glufosinate-tolerant crops of maize (Zea mays L ssp mays) and oilseed rape
      (Brassica napus L var napus).
AB  - The aim of the present study was to determine whether post-emergence application
      of glufosinate to transgenic crops could lead to an increase in residues or to
      the formation of new, hitherto unknown metabolites. Transgenic oilseed rape and
      maize plants were treated separately with L-glufosinate, D-glufosinate or the
      racemic mixture. Whereas about 90% of the applied D-glufosinate was washed off by
      rain and only 5-6% was metabolised, 13-35% of the applied L-glufosinate remained
      in the form of metabolites and unchanged herbicide in both transgenic maize and
      oilseed rape. The main metabolite was N-acetyl-L-glufosinate with total residues
      of 91% in oilseed rape and 67% in maize, together with small amounts, of 5% in
      oilseed rape and 28% in maize, of different methylphosphinyl fatty acids. These
      metabolites were probably formed from L-glufosinate by deamination and subsequent
      decarboxylation. The residues were distributed in all fractions of the plants,
      with the highest contents in treated leaves and the lowest in the grains (0.07
      0.3% in maize and 0.4-0.6% in oilseed rape). There was no indication of an
      accumulation of total residues or of residue levels above the official tolerances
      for glufosinate.

PMID- 15260302
TI  - Synthesis and insecticidal activity of 5-acyloxyimino-5-deoxyavermectin B1
      derivatives.
AB  - Four novel 5-acyloxyimino-5-deoxyavermectin B1 compounds have been synthesized
      from avermectin B1 by selective oxidization of the hydroxy group at C-5, followed
      by oximation and convenient esterification. Their structures were confirmed by
      IR, 1H NMR, 13C NMR and MS. Insecticidal activities of the intermediate oxime and
      the four new acyl derivatives were evaluated against Helicoverpa armigera,
      Spodoptera exigua and Musca domestica.

PMID- 15260303
TI  - Tebuconazole dissipation and metabolism in Tifton loamy sand during laboratory
      incubationt.
AB  - The fungicide tebuconazole is widely used to control soil-borne and foliar
      diseases in peanuts and other crops. No published data are currently available on
      the extent and rate at which this compound degrades in soil. Unpublished data
      summarized in registration documents suggest that the compound is persistent,
      with 300-600 days half-life. We conducted a 63-day laboratory incubation to
      evaluate tebuconazole's dissipation kinetics and impact on soil microbial
      activity in Tifton loamy sand. Tifton soils support extensive peanut production
      in the Atlantic Coastal Plain region of Georgia and Alabama. Products containing
      tebuconazole are applied to an estimated 50% of the peanut acreage in the region.
      At the end of the incubation, 43 (+/-42)% of the parent compound was recovered in
      soil extracts. The first-order kinetic model, which gave a good fit to the
      dissipation data (r2 = 0.857), yielded a soil half-life (t1/2) of 49 days. This
      is 6-12 times more rapid than t1/2 values described in unpublished tebuconazole
      registration documents. Four degradates were identified. Tentative structural
      assignments indicated that degradates were derived from hydroxylation of the
      parent compound and/or chlorophenyl ring cleavage. Cleavage products showed a
      steady increase during the incubation, and on a molar basis were equal to 63% of
      the time zero tebuconazole concentration. No significant effect on soil microbial
      biomass was observed, indicating that when the compound is applied at normal
      agronomic rate it does not impact soil metabolic activity. Use of the soil-half
      life data derived in this study should improve the accuracy oftebuconazole fate
      assessments for Coastal Plain peanut production. The study also indicated that
      environmental assessment of selected degradates may be needed to fully evaluate
      risks of tebuconazole use.

PMID- 15260304
TI  - The interaction of endosulfan with the Collembolan, Proisotoma minuta (Tullberg):
      toxicity, the effects of sub-lethal concentrations and metabolism.
AB  - An increased level of the Collembolan, Proisotoma minuta Tullberg was found in
      the cotton-growing areas of New South Wales, Australia. They were regularly
      exposed to endosulfan, a highly insecticidal compound. Toxicity, sub-lethal
      effects and metabolism of endosulfan were studied in P minuta that had been
      successfully maintained in a plaster of Paris and charcoal mixture substrate with
      freeze-dried yeast as a food. The 168-h LD50 values were 0.011, 0.049 and 0.055
      mg liter(-1) for alpha- and beta-endosulfan and endosulfan sulfate, respectively.
      When P minuta were exposed to non-lethal concentrations of the endosulfans, egg
      production was inhibited. On recovery from the toxic effects of the endosulfans
      they resumed production of viable eggs. Conversion of alpha- and beta-endosulfan
      to endosulfan sulfate was found and the endosulfan sulfate could be further
      metabolized. The rate of metabolism of alpha-endosulfan was greater than that of
      beta-endosulfan and the product of endosulfan sulfate metabolism was not
      identified.

PMID- 15260305
TI  - Responses of the olfactory receptor neurons of the corn stalk borer Sesamia
      nonagrioides to components of the pheromone blend and their inhibition by a
      trifluoromethyl ketone analogue of the main component.
AB  - Two types of olfactory hairs and three types of olfactory receptor neurons (ORN)
      have been characterized on the antennae of male Sesamia nonagrioides Lef for the
      first time. Type A sensilla housed a cell which fired large spikes in response to
      (Z)-11-hexadecenyl acetate (Z11-16:Ac), the major component of the sex pheromone,
      and a second cell firing smaller spikes in response to (Z)-11-hexadecenal (Z11
      16:Ald), a minor component of the pheromone blend. Type B sensilla housed one
      cell firing large spikes to Z11-16:Ac and a cell firing smaller spikes to another
      minor component of the pheromone blend, (Z)-11-hexadecenyl alcohol (Z11-16:OH).
      No cell responding to dodecyl acetate, another minor component of the natural
      extract, was found. Fluorinated ketones were tested as inhibitors of the cell
      responses to pheromone compounds. The fluorinated derivatives tested, (Z)-11
      hexadecenyl trifluoromethyl ketone (Z11-16:TFMK), n-hexadecyl trifluoromethyl
      ketone (16:TFMK), (Z,E)-9,11-tetradecadienyl trifluoromethyl ketone (Z9,E11
      14:TFMK), 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP), (Z)-11-tetradecenyl
      trifluoromethyl ketone (Z11-11:TFMK) and 1,1-difluoro-(Z)-11-hexadecenyl methyl
      ketone (Z11-16:DFMK), had no or only weak excitatory effects. However, the neuron
      responses to the pheromone compounds were significantly decreased in the presence
      of a constant stimulation with Z11-16:TFMK and the effect was reversible. The
      latencies of the responses to the acetate and aldehyde cells were significantly
      increased. The effects were not specific, since Z11-16:TFMK also inhibited the
      responses of the ORNs of Spodoptera littoralis Boisd. Correspondingly, Z9,E11
      14:TFMK, an analogue of the main component of the pheromone of this latter
      insect, inhibited responses of S nonagrioides ORNs. Implications of these results
      on the utilization of Z11-16:TFMK as a communication disruptant are discussed.

PMID- 15260306
TI  - Decision making in controlling virus yellows of sugar beet in the UK.
AB  - Virus yellows is an important disease affecting yield in sugar beet in the UK.
      Myzus persicae (Sulzer) is the most effective and efficient aphid vector of the
      three viruses causing the disease: beet yellows virus, beet mild yellowing virus
      and beet chlorosis virus. Control of virus yellows disease is thus focused on the
      study and control of this aphid species. UK national surveys of virus yellows
      began in 1946 and these data helped to formulate disease forecasting schemes to
      optimise control. Over the years, in addition to improvements in farm hygiene,
      periodic changes and developments in control of the disease have occurred. To
      accommodate these important developments, virus yellows forecasting schemes have
      evolved accordingly. The most recent version has been adapted to take account of
      the current widespread use of imidacloprid seed treatment. Its application offers
      potential to optimise the rational use of aphicides such as imidacloprid so as to
      benefit beet growers and the environment by reducing prophylactic use of seed
      treatment.

PMID- 15260307
TI  - Another brominated flame retardant in the environment.

PMID- 15260308
TI  - Arctic chemistry may explain perfluorinated mystery.

PMID- 15260309
TI  - Ozone pollutant phaseout delayed.

PMID- 15260310
TI  - Scientists analyze the problems of world's poor.

PMID- 15260311
TI  - Common fern may aid communities coping with arsenic contamination.

PMID- 15260312
TI  - Nocturnal chemistry removes NOx.

PMID- 15260313
TI  - Federal buildings increasingly going green.

PMID- 15260314
TI  - Plumbing the depths of D.C.'s drinking water crisis.

PMID- 15260315
TI  - Defining bioavailability and bioaccessibility of contaminated soil and sediment
      is complicated.

PMID- 15260316
TI  - CO2 emission benefit of diesel (versus gasoline) powered vehicles.
AB  - Concerns regarding global warming have increased the pressure on automobile
      manufacturers to decrease emissions of CO2 from vehicles. Diesel vehicles have
      higher fuel economy and lower CO2 emissions than their gasoline counterparts.
      Increased penetration of diesel powered vehicles into the market is a possible
      transition strategy toward a more sustainable transportation system. To
      facilitate discussions regarding the relative merits of diesel vehicles it is
      important to have a clear understanding of their CO2 emission benefits. Based on
      European diesel and gasoline certification data, this report quantifies such CO2
      reduction opportunities for cars and light duty trucks in today's vehicles and
      those in the year 2015. Overall, on a well-to-wheels per vehicle per mile basis,
      the CO2 reduction opportunity for today's vehicles is approximately 24-33%. We
      anticipate that the gap between diesel and gasoline well-to-wheel vehicle CO2
      emissions will decrease to approximately 14-27% by the year 2015.

PMID- 15260317
TI  - Estimation of the production, consumption, and atmospheric emissions of
      pentabrominated diphenyl ether in Europe between 1970 and 2000.
AB  - A European consumption and atmospheric emissions inventory for pentabrominated
      diphenyl ethers (PeBDEs) is derived for the period 1970-2000. This time frame has
      seen a rise in the widespread usage of PeBDE, followed by more recent
      restrictions/bans. It is estimated that a total of 3000-5000 t of PeBDEs was
      produced in Europe during this period, with a further 9000-10,000 t imported in
      finished articles. The main uses for PeBDE are to flame retard consumer products
      as well as in packaging and solid elastomers. Their major stocks are predicted to
      be in polyurethane (flexible) foams with up to 30% in cars; more than 10% in
      furniture foam; and the rest in textiles, building material, packaging, and solid
      applications. Release of PeBDEs from treated products into environmental media
      are estimated with a focus on atmospheric inputs via volatilization from their
      use in cars, upholstered furniture, textiles, television sets, personal
      computers, and other recycled material. Different emission factors are used to
      derive different emission scenarios. A peak in atmospheric emissions of between
      22 and 31 t of BDE-47 is estimated to have occurred around 1997, with a decline
      of approximately 20% in 2000. Comparisons with long-term environmental monitoring
      data revealed that the time trends of human blood and milk concentrations follow
      similar patterns to the generated emissions, while sediment core levels increase
      more slowly, probably because they respond to a mix of atmospheric and catchment
      inputs. The emissions data derived here can be used in a spatially and temporally
      resolved form as input data for multi-media environmental fate modeling.

PMID- 15260318
TI  - PCB loading from sediment in the Hudson River: congener signature analysis of
      pathways.
AB  - The upper Hudson River (NY) was subjected to massive PCB contamination over a
      period of three decades. A large inventory of PCBs remains in contaminated
      sediments of the river, most notably in the Thompson Island Pool. During the
      summer, flow crossing the Thompson Island Pool exhibits a large and consistent
      PCB load gain. This load gain is not associated with scouring flows and is not
      accompanied by an increase in suspended solids. A variety of hypotheses have been
      proposed to explain this load gain, including flux of contaminated porewater and
      dissolution of unverified reservoirs of pure PCBs. A wealth of congener-specific
      PCB data is available for the site throughout the 1990s. Interpretation of the
      Thompson Island Pool load gain is facilitated by examination of the PCB congener
      signature of the gain and comparison to the signature of potential sources. This
      examination suggests that neither the flux of porewater nor the dissolution of
      unaltered Aroclors are the predominant source of the load gain. Instead, the
      congener signature is consistent with a mixed source consisting of porewater flux
      and non-scour flux of contaminated sediments. The non-scour sediment flux, which
      reaches a maximum in the beginning of the summer growing season, is likely driven
      by a variety of biological and anthropogenic processes, including bioturbation by
      benthic organisms, bioturbation by demersal fish, scour by propwash, mechanical
      scour by boats and floating debris in nearshore areas, and uprooting of
      macrophytes.

PMID- 15260319
TI  - Landscape-level approach to assess aquatic exposure via spray drift for
      pesticides: a case study in a Mediterranean area.
AB  - The development of methods to extract information from landscape analysis to
      refine risk assessment is becoming increasingly important. This paper presents
      results from a pesticide surface water exposure assessment at the watershed
      scale, based on a combination of edge of field studies, large-scale monitoring
      studies, and modeling activities with GIS-based landscape analysis methodologies
      covering an area of approximately 3200 ha surrounding the Simeto River in Sicily
      (Italy). The dynamic behavior of the pesticide chlorpyrifos-methyl was modeled in
      two different steps: calculation of the fraction of the application rate that is
      deposited beyond the field edge and simulation of the fate and persistence of the
      pesticide in the aquatic environment. Drift loads showed high spatial
      variability. Considering spray drift deposition as a fraction of the pesticide
      application rate, 60% of the results were < or = 0.02 (equal to 0.04 mg/m2). Only
      8.5% of the results were above 0.5. The highly variability of the landscape
      factors was reflected in the results. More than 60% of the predicted pesticide
      concentrations were less than the limit of quantification (0.05 microg/L),
      affecting about 75% of the total length of the river tract analyzed. Predicted
      pesticide concentrations were higher than 0.1 microg/L in 23% of cases, but this
      corresponded to an insignificant portion of the river (1.2% of the total length).
      These results suggest that management options, such as increased no-spray zones,
      could provide further protection for surface water. These could be modeled to
      illustrate their overall impact. As an alternative, the introduction of a 20-m no
      spray zone clearly reduced potential exposure, and 92% of the water body was
      protected. Estimated data are in agreement with data collected during a field
      monitoring study.

PMID- 15260320
TI  - Identification of the flame retardant decabromodiphenyl ethane in the
      environment.
AB  - The brominated flame retardant decabromodiphenyl ethane, DeBDethane, is marketed
      as an alternative to decabromodiphenyl ether, BDE209. There are currently no data
      available about the presence of DeBDethane in the environment. In this study,
      DeBDethane was positively identified by high-resolution mass spectrometry and
      quantified by low-resolution mass spectrometry with electron capture negative
      ionization in sewage sludge, sediment, and indoor air. It was found in 25 of the
      50 Swedish sewage treatment plants investigated, with estimated levels up to
      about 100 ng/g dry weight. The concentration of DeBDethane in sediment from
      Western Scheldt in The Netherlands was 24 ng/g dry weight, and in an air sample
      from a Swedish electronics dismantling facility it was 0.6 ng/m3. DeBDethane was
      also found together with nonabromodiphenyl ethanes in water piping insulation.
      All samples contained BDE209 in higher concentrations as compared to DeBDethane
      (DeBDethane/BDE209 ratios ranging from 0.02 to 0.7), probably reflecting the
      higher and longer usage of BDE209. There is an ongoing risk assessment within the
      European Union regarding BDE209. Since DeBDethane has similar applications, it is
      important to investigate its environmental behavior before using it to replace
      BDE209.

PMID- 15260321
TI  - Fertilizer characterization: isotopic data (N, S, O, C, and Sr).
AB  - A detailed isotopic characterization (delta15N(Ntotal), delta15N(NO3),
      delta18O(NO3), delta34S(SO4), delta18O(SO4), (delta13C(Ctotal), and 87Sr/86Sr) of
      27 commercial fertilizers used in Spain is presented in this paper. Results
      together with a compilation of fertilizer isotopic published data are used for
      two purposes: (i) to identify the origin of the primary constituents and raw
      materials used in fertilizer manufacture and relate these data with their heavy
      metals and rare earth elements (REE) contents; (ii) to compare the fertilizer
      isotopic signatures with natural values and other anthropogenic pollutants and
      evaluate the usefulness of multi-isotopic analyses to trace fertilizer
      contaminations in future study cases. Isotope data permit us to know, in most
      cases, the origin of the primary constituents of fertilizers, and the 87Sr/86Sr
      ratio distinguishes the origin of the phosphate content--phosphorites or
      carbonatites--which in turn implies a qualitatively defined and potentially
      contaminant presence of REE and heavy metals in fertilizers. Delta15N, delta34S,
      and 87Sr/86Sr have already been used to trace fertilizer contaminations. Their
      utility can be improved by the coupled use of delta15N(NO3)-delta18O(NO3) and
      delta34S(SO4)-delta18O(SO4) to evaluate the fractionation processes that can
      affect contaminants. Moreover, multi-isotopic analyses, using heavy isotopes,
      allow us to see beyond the fractionation effects to the fertilizer stable isotope
      signatures and a better distinction from other anthropogenic contaminants.

PMID- 15260322
TI  - Herbicide runoff along highways. 1. Field observations.
AB  - Herbicides are widely applied along highways to control roadside vegetation, and
      surface water is frequently nearby. To determine whether herbicide runoff along
      highways threatens water quality, a field study was conducted at two sites in
      northern California for three rainy seasons. The herbicides oryzalin, isoxaben,
      diuron, glyphosate, and clopyralid were selected for study to include compounds
      with significant variation in physical/chemical properties. Concentrations of
      herbicides in runoff were monitored for up to 11 storms following herbicide
      application, and 24 samples were collected per storm, providing unprecedented
      temporal detail. Flow-weighted event mean concentrations were calculated for each
      herbicide in each storm and ranged from below detection limits to 43.13 microg/L
      for oryzalin. The least soluble compounds, isoxaben and oryzalin, were detected
      in all storms monitored while the more soluble compounds, diuron and clopyralid,
      declined to levels below detection limits before monitoring was concluded. Very
      small amounts of glyphosate were mobilized, but its transformation product
      aminomethylphosphonic acid was detected at higher concentrations, in more storm
      events, and at greater depth in the soil profile. A first-order model
      successfully described the declining herbicide concentrations in spray zone soil
      and in surface runoff for all sites and herbicides. Fitted first-order
      coefficients were always higher for runoff than for soil, indicating that the
      herbicide that persists in the source zone becomes less available for runoff as
      the time since application increases. The percentage of the applied herbicide
      that was detected in surface runoff over a season ranged from 0.05% to 43.5%, and
      the most critical variables in controlling the variation were the solubility of
      the herbicide and the runoff volume. For a given herbicide and site, the most
      critical factors in determining seasonal herbicide loss to surface water were the
      timing and intensity of the first storm following application, affecting total
      seasonal runoff by up to 2 orders of magnitude. Minimizing runoff of herbicides
      along highways will thus require careful attention to the intrinsic mobility of
      the compound and the timing of its application.

PMID- 15260323
TI  - Herbicide runoff along highways. 2. Sorption control.
AB  - Controversy remains about the importance of nonlinear sorption isotherms,
      desorption rate limitations, and aging effects, collectively referred to as
      nonideal sorption processes, in controlling the fate and transport of organic
      contaminants. Herbicide runoff from highway soils represents a good test case for
      assessing the relative importance of nonideal sorption because runoff flow rates
      are often high, soil-water contacttimes are short, and significant time is
      available for contaminant aging after application. This study examines the
      sorption and desorption of five herbicides with a wide range of properties
      (isoxaben, oryzalin, diuron, clopyralid, and glyphosate) on soil samples from two
      roadsides in northern California and uses the results to examine field runoff
      data from multiple rainy seasons. Nonideal sorption processes do not appear to be
      significant in determining herbicide runoff at the field sites because (i)
      sorption isotherms were linear or slightly nonlinear for all compounds but
      glyphosate, (ii) field runoff concentration ratios between isoxaben and oryzalin
      were consistent with linear partitioning predictions, (iii) runoff leaving the
      site appeared to be in equilibrium with local soil concentrations, and (iv)
      desorption distribution coefficients for aged herbicides on soil samples
      collected from the field site did not differ substantially from those obtained in
      short-term laboratory adsorption experiments. Collectively, these findings
      indicate that linear equilibrium models are adequate for predicting the
      concentration of herbicides in runoff in these field settings and that more
      complicated nonideal models do not need to be invoked. Vegetated slopes
      effectively reduced the herbicide loads, with average removals of 35-80%
      occurring as runoff traversed a 3-m segment 1 m from the edge of the spray zone.

PMID- 15260324
TI  - Quantitative source identification of dioxin-like PCBs in Yokohama, Japan, by
      temperature dependence of their atmospheric concentrations.
AB  - The source and environmental behavior of dioxin-like polychlorinated biphenyls
      (PCBs) together with other PCBs and polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDDs/PCDFs) were evaluated based on analysis of variations in
      their atmospheric concentrations in Yokohama, Japan. Potential factors
      responsible for variations in the atmospheric concentrations of the congeners
      were investigated by principal component analysis and multiple regression
      analysis of the data. Two major variations were seen: one had strong temperature
      dependence, while the other had no significant temperature dependence. A possible
      explanation for this difference is that the former is related to congeners
      released by volatilization (e.g., volatilization from commercial PCB products and
      past polluted environments), while the latter is related to congeners emitted
      from thermal processes. The relative contributions of dioxin-like PCBs released
      by volatilization and those emitted from thermal processes were estimated based
      on the temperature dependence of the atmospheric concentrations. The results
      suggest that both dioxin-like PCBs emitted from thermal processes and those
      released by volatilization are significant sources of air pollution in this area
      in terms of the toxic equivalent (TEQ) for dioxin-like PCBs. We demonstrated that
      the present approach based on variations in atmospheric concentrations can be
      useful in providing a qualitative as well as quantitative understanding of source
      information.

PMID- 15260325
TI  - Polybrominated diphenyl ethers in the sediments of the Great Lakes. 1. Lake
      Superior.
AB  - Sediment cores were taken in 2001 and 2002 in Lake Superior at six locations away
      from lakeshores and segmented at 0.5-5 cm intervals. The year of sediment
      deposition was estimated for each segment of four cores using the 210Pb dating
      technique. Samples were Soxhlet-extracted and cleaned up by silica gel
      fractionation, and the concentrations of 10 polybrominated diphenyl ethers
      (PBDEs) and 19 polychlorinated biphenyls (PCBs) were measured by GC-MS in SIM
      mode. In contrast to recent declining or level-off trends in PCB fluxes, the
      sedimentary records of PBDEs generally show a significant increase in recent
      years. The load of total PBDEs to Lake Superior was estimated to be 2-6 metric
      tons, and the current loading rate was about 80-160 kg yr(-1). With the exclusion
      of decabromodiphenyl ether (BDE209), the surficial concentration of sumPBDE (sum
      of 9 congeners) ranged from 0.5 to 3 ng g(-1), and the current sumPBDEs flux was
      8-31 pg cm(-2) yr(-1). The concentrations of BDE209 were about an order of
      magnitude higher than the sum of other congeners, comprising 83-94% of the total
      PBDE inventory in the sediments. Among the other nine PBDEs detected, congeners
      47 and 99 were the most abundant, and congeners 100, 153, 154, and 183 were also
      detected in all the cores. Congener analysis demonstrated that the pattern of
      PBDEs in Lake Superior sediments differs from those in air and fish.

PMID- 15260326
TI  - Sources of polycyclic aromatic hydrocarbons and hexachlorobenzene in spruce
      needles of eastern Alaska.
AB  - The concentrations of phenanthrene, anthracene, fluoranthene, pyrene,
      benzo[a]anthracene, chrysene, and hexachlorobenzene (HCB) were measured in spruce
      needles at 36 sites in eastern Alaska during early spring. Concentrations of each
      polycyclic aromatic hydrocarbon (PAH) varied by an order of magnitude. Samples
      taken from near the city of Fairbanks had higher concentrations than samples
      taken from more rural areas. Anthropogenic activities near Fairbanks are most
      likely a source of PAHs. Variation in the concentration ratios of isomeric PAHs
      indicates the relative importance of combustion and petrogenic sources. The
      relative combustion contribution is largest in coastal samples and smallest near
      Fairbanks. In contrast, the concentration of HCB varied by only a factor of 2.
      Lipid content of needles and distance from the coast were the major factors
      correlated with the concentration of HCB.

PMID- 15260327
TI  - Arsenite retention mechanisms within estuarine sediments of Pescadero, CA.
AB  - Arsenic, a toxic metalloid, is commonly associated with sulfide minerals in
      anoxic sediments. Here we characterize arsenic(III) retention on sediments from a
      sulfidic estuarine marsh using a series of sorption experiments, and probe the
      structure of retained arsenite with X-ray absorption spectroscopy. Although the
      extent of sorption varied with sampling locations, several adsorption
      characteristics were apparent. A fraction of arsenite adsorbed over the entire pH
      range examined, although it was most extensive at pH greater than 7, and
      conformed to a Langmuir isotherm. Iron sulfide phases were responsible for As
      partitioning in these sediments. Initially, an FeAsS-like precipitate formed with
      a structure similar to those reported for As(III) sorbed on iron sulfides, a
      complex that is highly reactive. Following reaction for 21 d, much of the FeAsS
      like precipitate was converted to As2S3. A drop in the redox potential
      accompanied this conversion, suggesting that the evolution of sulfide and other
      reduced species stabilizes bound arsenic. Processes discerned in this study
      reveal the importance of sulfide minerals in As sequestration within anoxic
      environments.

PMID- 15260328
TI  - Modeling maximum adsorption capacities of soot and soot-like materials for PAHs
      and PCBs.
AB  - Recent studies have shown that not partitioning but adsorption is the main
      mechanism for sorption of hydrophobic organic compounds to soot and soot-like
      materials. For compounds that adsorb by van derWaals forces only, variation in
      soot-water distribution coefficients will result from differences in these forces
      for adsorption, as well as the maximum number of accessible sites. This maximum
      number of accessible sites may a priori be expected to vary due to differences in
      both sorbent characteristics and sorbate dimensions. In this modeling study,
      variation in maximum adsorption capacities is explained from sorbent and sorbate
      properties. Maximum adsorption capacities were calculated using (a) literature
      values for soot-water distribution coefficients for polycyclic aromatic
      hydrocarbons and polychlorobiphenyls on 10 different soot and soot-like materials
      and (b) Langmuir affinities for adsorption at a carbonaceous surface estimated
      using a recently reported method. The variation in maximum adsorption capacities
      could be explained by the variation in sorbent specific surface area, sorbent
      organic carbon content, and the sorbent-sorbate contact area. Furthermore,
      increasing sorbate thickness was related to a decrease in maximum adsorption
      capacities, which points to adsorption in micropores. Maximum adsorption
      capacities decreased by 1-2 orders of magnitude as the contact area increased by
      50%. This points to adsorption sites being hardly larger than sorbates.

PMID- 15260329
TI  - Evidence of uranium and associated trace element mobilization and retention
      processes at Oklo (Gabon), a naturally radioactive site.
AB  - The processes that affect the mobility of uranium and other radionuclides in the
      environment have been largely studied at both the laboratory and the field
      scales. The natural reactors found at the Oklo uranium mine in Gabon constitute a
      unique investigation setting as spontaneous fission reactions occurred two
      billion years ago. Oklo uraninites contain a large amount of other radionuclides
      as a result of the fission process. We have investigated the dissolution behavior
      of four uraninite samples from Oklo as a function of temperature (25 and 60
      degrees C) and bicarbonate concentration (2.7-30 mmol/L). We have also
      investigated the dissolution behavior of minor components of the uraninites
      (i.e., Nd, Cs, Mo, Yb, and Sb) in relation to the dissolution of uranium. The
      results of the reported work are in good agreement with the kinetic rate laws
      derived from other uranium(IV) dioxide studies. Some of the minor components are
      found to be congruently released from the uraninite phase, while it is postulated
      that dissolution from segregated phases might affect the final concentrations of
      some of the rare earth elements, i.e., Nd and Yb. In addition, we have performed
      dissolution studies at 60 degrees C with two uraninites representative of
      different geochemical environments at Oklo, to study the uranium dissolution
      rates as a function of the temperature. This has allowed derivation of apparent
      activation energies for the bicarbonate-promoted oxidative dissolution of the
      Oklo uraninites. The dissolution behavior of the minor components of the
      uraninites at 60 degrees C was found to closely follow the behavior observed at
      25 degrees C. This indicates that similar codissolution mechanisms operate in the
      temperature range studied. The implications for the mobility of uranium and other
      radionuclides in natural and anthropogenic environments are discussed.

PMID- 15260330
TI  - Degradation of fluorotelomer alcohols: a likely atmospheric source of
      perfluorinated carboxylic acids.
AB  - Human and animal tissues collected in urban and remote global locations contain
      persistent and bioaccumulative perfluorinated carboxylic acids (PFCAs). The
      source of PFCAs was previously unknown. Here we present smog chamber studies that
      indicate fluorotelomer alcohols (FTOHs) can degrade in the atmosphere to yield a
      homologous series of PFCAs. Atmospheric degradation of FTOHs is likely to
      contribute to the widespread dissemination of PFCAs. After their bioaccumulation
      potential is accounted for, the pattern of PFCAs yielded from FTOHs could account
      for the distinct contamination profile of PFCAs observed in arctic animals.
      Furthermore, polar bear liver was shown to contain predominately linear isomers
      (>99%) of perfluorononanoic acid (PFNA), while both branched and linear isomers
      were observed for perfluorooctanoic acid, strongly suggesting a sole input of
      PFNA from "telomer"-based products. The significance of the gas-phase peroxy
      radical cross reactions that produce PFCAs has not been recognized previously.
      Such reactions are expected to occur during the atmospheric degradation of all
      polyfluorinated materials, necessitating a reexamination of the environmental
      fate and impact of this important class of industrial chemicals.

PMID- 15260331
TI  - Sorption of 17beta-estradiol and 17alpha-ethinylestradiol by colloidal organic
      carbon derived from biological wastewater treatment systems.
AB  - Sorption coefficients (K(COC)) between 17beta-estradiol (E2), 17alpha
      ethinylestradiol (EE2) and size-fractionated colloidal organic carbon (COC)
      derived from two biological wastewater treatment facilities were quantified by
      fluorescence quenching. The two wastewater treatment systems included a full
      scale activated sludge system (FSAS) and a membrane bioreactor (MBR). The K(COC)
      coefficients were highly variable and ranged between (<1 to 179) x 10(3) L/kgCOC
      for E2 and (<1 to 430) x 10(3) L/kgCOC for EE2 and were higher than expected from
      the analytes octanol-water partition coefficient. Correlations between the molar
      extinction coefficients measured at 280 nm (e280) and K(COC) coefficients were
      weak but stronger for E2 compared to EE2. Attempts at correlating sorption
      behavior with colloidal protein and polysaccharide concentrations were only
      marginally successful (r2 approximately 0.4). These low correlations suggest that
      aromatic content, protein, or polysaccharide concentration can not adequately
      explain E2 and EE2 sorption behavior to COC and that other fractions of the
      organic matter pool play an important role in binding. A substantial portion of
      the aqueous E2 and EE2 concentrations (up to 60%) may be associated with
      colloidal material, suggesting that COC may play a role in the fate and transport
      of E2 and EE2 during the activated sludge process.

PMID- 15260332
TI  - Identifying the sources of subsurface contamination at the Hanford Site in
      Washington using high-precision uranium isotopic measurements.
AB  - In the mid-1990s, a groundwater plume of uranium (U) was detected in monitoring
      wells in the B-BX-BY Waste Management Area at the Hanford Site in Washington.
      This area has been used since the late 1940s to store high-level radioactive
      waste and other products of U fuel-rod processing. Using multiple-collector ICP
      source magnetic sector mass spectrometry, high-precision uranium isotopic
      analyses were conducted of samples of vadose zone contamination and of
      groundwater. The isotope ratios 236U/238U, 234U/238U, and 238U/235U are used to
      distinguish contaminant sources. On the basis of the isotopic data, the source of
      the groundwater contamination appears to be related to a 1951 overflow event at
      tank BX-102 that spilled high-level U waste into the vadose zone. The U isotopic
      variation of the groundwater plume is a result of mixing between contaminant U
      from this spill and natural background U. Vadose zone U contamination at tank B
      110 likely predates the recorded tank leak and can be ruled out as a significant
      source of groundwater contamination, based on the U isotopic composition. The
      locus of vadose zone contamination is displaced from the initial locus of
      groundwater contamination, indicating that lateral migration in the vadose zone
      was at least 8 times greater than vertical migration. The time evolution of the
      groundwater plume suggests an average U migration rate of approximately 0.7-0.8
      m/day showing slight retardation relative to a groundwater flow of approximately
      1 m/day.

PMID- 15260333
TI  - Thermodynamics of peat-, plant-, and soil-derived humic acid sorption on
      kaolinite.
AB  - Humic acids (HAs) form coatings on clays and minerals that can play an important
      role in nutrient and contaminant migration in soil and water. Humic acid-clay
      mineral interactions are known to be affected by pH and ionic strength, but
      little attention has been paid to the effects of temperature. In this paper we
      report the stoichiometry and thermodynamics of interactions of aqueous HAs
      (isolated from two peats, two soils and a marine alga with a method that removes
      lipids) with kaolinite clay, Al2Si2O5(OH)4, at seven temperatures from 5.0 to
      35.0 degrees C in 0.05 M NaCl at pH 3.5. All the sorption isotherms exhibit
      consecutive steps ascribed to HA monolayer and bilayer formation, respectively.
      Site capacity comparisons suggest different HA molecular conformations on
      kaolinite. Linearly correlated enthalpy and entropy changes for HA sorption point
      to the importance of hydration and dehydration in the sorption mechanism.

PMID- 15260334
TI  - Secondary organic aerosol formation from cyclohexene ozonolysis: effect of OH
      scavenger and the role of radical chemistry.
AB  - To isolate secondary organic aerosol (SOA) formation in ozone-alkene systems from
      the additional influence of hydroxyl (OH) radicals formed in the gas-phase ozone
      alkene reaction, OH scavengers are employed. The detailed chemistry associated
      with three different scavengers (cyclohexane, 2-butanol, and CO) is studied in
      relation to the effects of the scavengers on observed SOA yields in the ozone
      cyclohexene system. Our results confirm those of Docherty and Ziemann that the OH
      scavenger plays a role in SOA formation in alkene ozonolysis. The extent and
      direction of this influence are shown to be dependent on the specific alkene. The
      main influence of the scavenger arises from its independent production of HO2
      radicals, with CO producing the most HO2, 2-butanol an intermediate amount, and
      cyclohexane the least. This work provides evidence for the central role of
      acylperoxy radicals in SOA formation from the ozonolysis of alkenes and generally
      underscores the importance of gas-phase radical chemistry beyond the initial
      ozone-alkene reaction.

PMID- 15260335
TI  - Environmental risk assessment of paroxetine.
AB  - Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a
      pharmaceutical compound used for the treatment of depression, social anxiety
      disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety
      disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of
      the parent compound being excreted as metabolites through the urine and feces of
      patients. Therefore PA and metabolites have the potential to be discharged into
      wastewater treatment systems after therapeutic use. PA and its major human
      metabolite (PM) were investigated using studies designed to describe
      physical/chemical characteristics and determine their fate and effects in the
      aquatic environment. A significant portion of the PM entering a wastewater
      treatment plant would be expected to biodegrade given the higher activated sludge
      solids concentrations present in a typical wastewater treatment plant. The
      potential for direct photolysis of PM is also possible based on photolysis
      results for PA itself. These results provide strong support for expecting that PA
      and PM residuals will not persist in the aquatic environment after discharge from
      a wastewater treatment facility. This conclusion is also supported by the results
      of a USGS monitoring study, where no PM was detected in any of the samples at the
      260 ng/L reporting limit. The results presented here also demonstrate the
      importance of understanding the human metabolism of a pharmaceutical so that the
      appropriate molecule(s) is used for fate and effects studies. In addition to the
      PA fate studies, PM was investigated using studies designed to determine
      potential environmental effects and a predicted no effect level (PNEC). The
      average measured activated sludge respiration inhibition value (EC50) for PM was
      82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna
      EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L.
      Fate data were then used in a new watershed-based environmental risk assessment
      model, PhATE, to predict environmental concentrations (PECs). Comparison of the
      calculated PECs with the PNEC allows an assessment of potential environmental
      risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged
      from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from
      approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of
      safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk
      to the environment. In addition, Microtox studies carried out on PM
      biodegradation byproducts indicated no detectable residual toxicity. Any
      compounds in the environment as a result of the biodegradation of PM should be
      innocuous polar byproducts that should not exert any toxic effects.

PMID- 15260336
TI  - Depolymerization of chromophoric natural organic matter.
AB  - Although the importance of natural organic matter (NOM) in the environment and in
      drinking water treatment is well-known, its structure is still ill-defined. The
      fragmentation patterns of NOM treated by irradiation (various wavelengths--185
      400 nm), hydroxyl radicals, chlorine, ozone, and breakdown by a white rot fungus
      were studied to investigate the structure of chromophoric NOM molecules. Size
      exclusion chromatography was used to monitor the size distributions of NOM in two
      natural water waters and two NOM isolates. Three distinct fragmentation patterns
      were observed: ozone attack appeared to be nonsize specific, UV (> or = 254 nm)
      irradiation preferentially removed higher molecular weight chromophores, while
      processes involving hydroxyl radical showed intermediate size specificity. For
      the samples studied, the UV (> or = 254 nm) irradiation-induced fragmentation of
      NOM followed the patterns suggested by a simple trimer depolymerization model,
      supporting the viewpoint that NOM has repeating structural units joined by
      photolabile chemical bonds. The largest molecules reacted most rapidly,
      progressively fragmenting into slower reacting smaller molecules, which initially
      accumulated before breaking down to become nonchromophoric. This dependency of
      rate on molecular size appears to follow from the law of photochemistry which
      states the rate of reaction is proportional to the rate of light absorption:
      larger chromophores had higher molar absorptivities, absorbed more photons, and
      hence reacted faster than smaller chromophores.

PMID- 15260337
TI  - Estimating potential environmental loadings of Cryptosporidium spp. and
      Campylobacter spp. from livestock in the Grand River Watershed, Ontario, Canada.
AB  - Exposure to waterborne pathogens in recreational or drinking water is a serious
      public health concern. Thus, it is important to determine the sources of
      pathogens in a watershed and to quantify their environmental loadings. The
      natural variability of potentially pathogenic microorganisms in the environment
      from anthropogenic, natural, and livestock sources is large and has been
      difficult to quantify. A first step in characterizing the risk of nonpoint source
      contamination from pathogens of livestock origin is to determine the potential
      environmental loading based on animal prevalence and fecal shedding intensity.
      This study developed a probabilistic model for estimating the production of
      Cryptosporidium spp. and Campylobacter spp. from livestock sources within a
      watershed. Probability density functions representing daily pathogen production
      rates from livestock were simulated for the Grand River Watershed in southwestern
      Ontario. The prevalence of pathogenic microorganisms in animals was modeled as a
      mixture of beta-distributions with parameters drawn from published studies.
      Similarly, gamma-distributions were generated to describe animal pathogen
      shedding intensity. Results demonstrate that although cattle are responsible for
      the largest amount of manure produced, other domesticated farm animals contribute
      large numbers of the two pathogenic microorganisms studied. Daily pathogen
      production rates are highly sensitive to the parameters of the gamma
      distributions, illustrating the need for reliable data on animal shedding
      intensity. The methodology may be used for identifying source terms for pathogen
      fate and transport modeling and for defining and targeting regions that are most
      vulnerable to water contamination from pathogenic sources.

PMID- 15260338
TI  - Equilibrium-based sampler for determining Cu2+ concentrations in aquatic
      ecosystems.
AB  - The bioavailability of potentially toxic metals in aquatic systems is frequently
      related to the dissolved free metal ion (M2+) concentration. However, typical
      methods used to determine M2+ are labor intensive or require sophisticated
      equipment. We developed an inexpensive, in situ sampling device--the "gellyfish"-
      that simplifies Cu2+ determinations in seawater. The gellyfish is a thin disk of
      polyacrylamide gel embedded with iminodiacetate (Id) groups bound to immobile
      beads. The sampler operates on the principle that the immobilized Id groups
      equilibrate with the Cu2+ concentration of the surrounding solution. Cu is then
      back-extracted into a known volume of 10% HNO3 and measured by inductively
      coupled plasma mass spectrometry (ICP-MS). In laboratory tests, we varied Cu2+
      concentrations between 10(-12) and 10(-8) M and salinity between 5 and 35 ppt. Id
      bound Cu (CuId(measured)) did not respond to changes in total Cu. However,
      CuId(measured) does increase in a predictable manner with increasing Cu2+, and
      prototype gellyfish precision (average coefficient of variation = 10%) is
      sufficient to resolve small differences in Cu2+ (+/-30%). Modeled Cu uptake,
      based on thermodynamic equilibrium speciation of Id within gellyfish, is a good
      predictor of CuId(measured) (r2 = 0.96 and n = 45).

PMID- 15260339
TI  - Identification of black carbon derived structures in a volcanic ash soil humic
      acid by Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry (FT-ICR MS), coupled with cross-polarization magic angle spinning
      13C nuclear magnetic resonance (NMR) spectroscopy and Kendrick mass defect
      analysis, was used to study the molecular composition of an aromatic carbon-rich
      humic acid extracted from a dark black soil from Iwata, Japan. Black carbon,
      produced by the incomplete combustion of fossil fuels and organic matter, has
      been suggested as a major component of humic acids having intense peaks in the
      aromatic and carboxyl regions of the 13C NMR spectrum. Taking advantage of the
      high resolving power of FT-ICR MS to make precise formula assignments, three
      different types of highly carboxylated polycyclic aromatic compounds were
      identified in the sample: linearly fused aromatic structures, aromatic structures
      linked by carbon-carbon single bonds, and highly condensed aromatic structures.
      These carboxylated aromatic structures have a low mass defect in their mass
      spectra due to their abundance of oxygen and deficiency of hydrogen. This mass
      defect is observed in the vast majority of peaks present in the entire mass
      spectrum, differentiating them from structures that are hydrogen-rich (e.g.,
      fatty acids, proteins, carbohydrates). Thus, we conclude that the bulk of the
      sample analyzed is comprised of these heavily carboxylated, hydrogen-deficient,
      condensed aromatic structures, features believed to be characteristic of black
      carbon-like material.

PMID- 15260340
TI  - Laboratory and field measurements of dry deposition of sulfur dioxide onto
      Chinese loess surfaces.
AB  - Laboratory and field measurements were conducted to examine dry deposition of SO2
      onto Chinese loess surfaces using native soil sampled in the loess plateau,
      China. The field tests were employed in Beijing and Lanzhou, China, by directly
      measuring the dry deposition of SO2 on soil, which uses soil put on a collector
      as an SO2 passive sampling medium. In the laboratory, a high rate of uptake to
      SO2 deposition for Chinese soil surfaces due to the highly alkalinity was found.
      The uptake of SO2 deposition was dependent on the pH soil and relative humidity.
      Furthermore, we evaluated some factors that affect the measurement precision:
      response of SO2 uptake, repeatability, recovery factor, and variability
      associated with the weight and the surface coverage on the collectors. As a
      result, it was shown that the measurement precision was primarily related to the
      ratio of the SO2 deposition amount relative to the sulfur content of the original
      soil. This result was consistent with the field observations. The laboratory and
      field results indicated an excellent agreement on the SO2 uptake inherent in the
      results from the soil surfaces in different regions.

PMID- 15260341
TI  - Contribution to the structural elucidation of 10 isomers of technical p
      nonylphenol.
AB  - Gas chromatography-mass spectrometry (GC-MS) with a 100 m capillary column at
      different oven temperatures is employed to separate isothermally p-nonylphenol
      into 21 isomers. Analysis of the resulting mass spectra of these isomers
      indicates that they could be classified into six groups with respect to different
      configurations of the alpha- and beta-C-atoms on the alkyl chains. Based on these
      basic structures nonylphenol isomers are synthesized and also characterized by GC
      MS. The obtained data elucidate the complete structures of 10 nonylphenol isomers
      of the technical mixture. The most important features of the mass spectra and the
      1H and 13C nuclear magnetic resonance (NMR) spectra of these isomers are
      presented.

PMID- 15260342
TI  - Phytofiltration of arsenic from drinking water using arsenic-hyperaccumulating
      ferns.
AB  - Arsenic contamination of drinking water poses serious health risks to millions of
      people worldwide. Current technologies used to clean arsenic-contaminated water
      have significant drawbacks, such as high cost and generation of large volumes of
      toxic waste. In this study, we investigated the potential of using recently
      identified arsenic-hyperaccumulating ferns to remove arsenic from drinking water.
      Hydroponically cultivated, two arsenic-hyperaccumulating fern species (Pteris
      vittata and Pteris cretica cv. Mayii) and a nonaccumulating fern species
      (Nephrolepis exaltata) were suspended in water containing 73As-labeled arsenic
      with initial arsenic concentrations ranging from 20 to 500 microg L(-1). The
      efficiency of arsenic phytofiltration by these fern species was determined by
      continuously monitoring the depletion of 73As-labeled arsenic concentration in
      the water. With an initial water arsenic concentration of 200 microg L(-1), P.
      vittata reduced the arsenic concentration by 98.6% to 2.8 microg L(-1) in 24 h.
      When the initial water arsenic was 20 microg L(-1), P. vittata reduced the
      arsenic concentration to 7.2 microg L(-1) in 6 h and to 0.4 microg L(-1) in 24 h.
      At similar plant ages, both P. vittata and P. cretica had similar arsenic
      phytofiltration efficiency and were able to rapidly remove arsenic from water to
      achieve arsenic levels below the new drinking water limit of 10 microg L(-1).
      However, N. exaltata failed to reduce water arsenic to achieve the limit under
      the same experimental conditions. The significantly higher efficiency of arsenic
      phytofiltration by arsenic-hyperaccumulating fern species is associated with
      their ability to rapidly translocate absorbed arsenic from roots to shoots. The
      nonaccumulating fern N. exaltata was unable to translocate the absorbed arsenic
      to the shoots. Our results demonstrate that the arsenic-phytofiltration technique
      may provide the basis for a solar-powered hydroponic technique that enables small
      scale cleanup of arsenic-contaminated drinking water.

PMID- 15260343
TI  - Thermal wet oxidation improves anaerobic biodegradability of raw and digested
      biowaste.
AB  - Anaerobic digestion of solid biowaste generally results in relatively low methane
      yields of 50-60% of the theoretical maximum. Increased methane recovery from
      organic waste would lead to reduced handling of digested solids, lower methane
      emissions to the environment, and higher green energy profits. The objective of
      this research was to enhance the anaerobic biodegradability and methane yields
      from different biowastes (food waste, yard waste, and digested biowaste already
      treated in a full-scale biogas plant (DRANCO, Belgium)) by assessing thermal wet
      oxidation. The biodegradability of the waste was evaluated by using biochemical
      methane potential assays and continuous 3-L methane reactors. Wet oxidation
      temperature and oxygen pressure (T, 185-220 degrees C; O2 pressure, 0-12 bar; t,
      15 min) were varied for their effect on total methane yield and digestion
      kinetics of digested biowaste. Measured methane yields for raw yard waste, wet
      oxidized yard waste, raw food waste, and wet oxidized food waste were 345, 685,
      536, and 571 mL of CH/g of volatile suspended solids, respectively. Higher oxygen
      pressure during wet oxidation of digested biowaste considerably increased the
      total methane yield and digestion kinetics and permitted lignin utilization
      during a subsequent second digestion. The increase of the specific methane yield
      for the full-scale biogas plant by applying thermal wet oxidation was 35-40%,
      showing that there is still a considerable amount of methane that can be
      harvested from anaerobic digested biowaste.

PMID- 15260344
TI  - Influence of electrostatics on the oxidation rates of organic compounds in
      heterogeneous Fenton systems.
AB  - Electrostatic effects influence the oxidation rates of charged dissolved organic
      compounds in systems where the hydroxyl radical (*OH) is produced by the iron
      oxide-catalyzed decomposition of hydrogen peroxide (H2O2). Experiments were
      performed using goethite and the *OH probes 14C-labeled formic acid, 2
      chlorophenol (2-CP), and nitrobenzene. At pH 4 and an ionic strength of 0.01 M,
      formic acid (pKa = 3.745) detected a steady-state concentration of *OH ([*OH]ss,
      calculated as a solution average) approximately 50 times higher than the two
      neutral probes did in the same systems, indicating significant enrichment of
      formate at the surface of the positively charged iron oxide where the *OH is
      being produced. Increasing the pH and ionic strength decreased formic acid
      oxidation rates by factors consistent with predicted decreases in electrostatic
      effects. In the presence of high 2-CP concentrations, the [*OH]ss measured by
      formic acid decreased with time, and goethite coagulation increased, due to loss
      of positive charge on the oxide surface as the oxidation products of 2-CP
      complexed surface Fe species. The [*OH]ss detected by 2-CP did not change
      significantly, indicating that neither goethite coagulation nor surface
      complexation of 2-CP oxidation products interfered with the rate of *OH
      generation; however, such an effect could have occurred in experiments using
      dissolved Fe instead of goethite. Model predictions of organic compound oxidation
      rates in mineral-catalyzed Fenton-like systems were improved by taking
      electrostatic effects into account.

PMID- 15260345
TI  - Inhibition of pyrite oxidation by a phospholipid in the presence of silicate.
AB  - The influence of sodium silicate on the ability of a diacetylene-containing
      phospholipid (23:2 diyne PC) to inhibit the oxidation of pyrite at pH 2 and pH 6
      was investigated. The phospholipid used has previously been reported to show up
      to 80% suppression of pyrite oxidation and to show excellent stability down to at
      least pH 2. Pyrite was leached with a solution containing Fe3+ but no coating
      agent and three different solutions or treatments: a lipid treatment, a silicate
      treatment, and a lipid + silicate treatment. Pyrite oxidation was based on iron
      (Fe3+, Fe2+) leached out of a continuous-flow porous-bed reactor system. The
      results show that at pH 6 the silicate and lipid both bind strongly to the pyrite
      surfaces, providing a barrier that inhibits the production and subsequent release
      of oxidation products. The lipid is superior to the silicate in suppressing
      pyrite oxidation at both pH 2 and pH 6. Also, the presence of silicates decreased
      the ability for the lipid to suppress pyrite oxidation, both at pH 2 and pH 6.
      The reaction mechanism for pyrite oxidation at pH 2 is first order for pyrite
      leached by solutions containing only ferric, ferric together with silicate, and
      ferric combined with silicate and lipid. The only treatment that effectively
      prevented pyrite oxidation at pH 2 was the lipid treatment. The Fe speciation
      results are supported by both SEM images and EDS calculations.

PMID- 15260346
TI  - Performance of a household-level arsenic removal system during 4-month
      deployments in Bangladesh.
AB  - A simple arsenic removal system was used in Bangladesh by six households for 4
      months to treat well water containing 190-750 microg/L As as well as 0.4-20 mg/L
      Fe and 0.2-1.9 mg/L P. The system removes As from a 16-L batch of water in a
      bucket by filtration through a sand bed following the addition of about 1.5 g of
      ferric sulfate and 0.5 g of calcium hypochlorite. Arsenic concentrations in all
      but 1 of 72 samples of treated water were below the Bangladesh drinking water
      standard of 50 microg/L for As. Approximately half of the samples also met the
      World Health Organization (WHO) guideline of 10 microg/L. At the two wells that
      did not meet the WHO guideline, observations were confirmed by additional
      experiments in one case ([P] = 1.9 mg/L) but not in the other, suggesting that
      the latter household was probably not following the instructions. Observed
      residual As levels are consistent with predictions from a surface complexation
      model only if the site density is increased to 2 mol/mol of Fe. With the
      exception of Mn, the average concentrations of other inorganic constituents of
      health concern (Cr, Ni, Cu, Se, Mo, Cd, Sb, Ba, Hg, Pb, and U) in treated water
      were below their respective WHO guideline for drinking water.

PMID- 15260347
TI  - MtBE biodegradation in a gravity flow, high-biomass retaining bioreactor.
AB  - The aerobic biodegradation of methyl tert-butyl ether (MtBE), a widely used fuel
      oxygenate, was investigated using a pilot-scale biomass-retaining bioreactor
      called a Biomass Concentrator Reactor (BCR). The reactor was operated for a year
      at a flow rate of 2500 L/d on Cincinnati dechlorinated tap water and an influent
      MtBE concentration of 5 mg/L. Treatment efficiency of MtBE in the reactor during
      stable operations exceeded 99.9%. The upper 95% confidence levels of effluent
      MtBE concentrations and its degradation byproduct tert-butyl alcohol (TBA) were
      2.9 and 0.9 microg/L, respectively, during these stable conditions. In addition,
      the effluent was found to be of better quality than the influent tap water as
      reflected by dissolved organic carbon analysis. Microbial community DNA profiling
      was carried out using denaturing gradient gel electrophoresis (DGGE) of
      polymerase chain reaction amplified 16s rDNA. The BCR was found to be inhabited
      by a wide spectrum of bacterial species, most notably microorganisms related to
      the genera Hydrogenophaga, Methylobacterium, Sphingomonas, and Pseudomonas. These
      organisms were previously reported to be associated with MtBE degradation. With
      the contamination of groundwater by MtBE being a wide-ranging problem throughout
      the United States, it is essential to develop a technology capable of effectively
      remediating such aquifers in order to protect public health and the environment.
      The BCR's simple operation and low maintenance requirements may render it an
      economically attractive approach to remediating groundwater contaminated with
      MtBE.

PMID- 15260348
TI  - Irritable bowel syndrome: a model of the brain-gut interactions.
AB  - Brain-gut interactions are increasingly recognized as underlying pathomechanisms
      of functional gastrointestinal disorders. Bi-directional communication between
      the central nervous system (CNS) and the enteric nervous system (ENS) occurs both
      in health and disease. Various CNS- and gut-directed stressors stimulate the
      brain-gut axis. Processes modulating responsiveness to stressors along the brain
      gut axis involve neural pathways, the immunological, and endocrinological
      mechanisms. Disturbances at every level of neural control of the gastrointestinal
      tract can affect modulation of gastrointestinal motility, secretion, immune
      functions as well as perception and emotional response to visceral events. ENS
      function, central processing, and autonomic regulation play an important role in
      the brain-gut dialogue. Stress and emotions may trigger neuroimmune and
      neuroendocrine reactions via the brain-gut axis. Various non-site specific
      neurotransmitters influence gastrointestinal, endocrine and immune function, as
      well as human behavior and emotional state, depending on their location. The
      physiology of the digestive tract, the subjective experience of symptom, health
      behavior, and treatment outcome are strongly affected by psychosocial factors.
      Recently, a biopsychosocial model of IBS containing physiological, emotional,
      cognitive and behavioral components has been proposed. Rapid progress in
      neurogastroenterology, using new brain imaging techniques, should bring better
      understanding of the brain-gut axis and open new therapeutic perspectives.

PMID- 15260349
TI  - Re: Open access publishing--panacea or Trojan horse?

PMID- 15260350
TI  - Lamellar keratectomy using an automated microkeratome.
AB  - PURPOSE: To evaluate the effectiveness of treating anterior corneal pathology by
      performing a superficial lamellar keratectomy with an automated microkeratome.
      METHODS: Retrospective chart review of 10 eyes (8 patients) seen in a
      subspecialty referral practice for anterior segment disease. With the use of an
      automated microkeratome, a lamellar flap was created, which was then surgically
      excised. RESULTS: Ten eyes of eight patients were followed for a mean of 5.4
      months (range, 4 to 10 months). Subjective visual acuity and/or sensation of
      ocular irritation improved in 10 of 10 eyes. Mean improvement in Snellen best
      corrected visual acuity was 1.8 lines (range, -1 to +3 lines). One patient lost 1
      line of Snellen acuity due to progression of a posterior subcapsular cataract.
      Mean change in spherical equivalent was +0.5 diopters (range, -1.60 to +4.25
      diopters), and mean improvement in corneal clarity (1 to 4 scale) was 1.8. Mean
      preoperative pachymetry was 589.0 microm (range, 507 to 741 microm). Mean
      postoperative pachymetry was 461.3 microm (range, 370 to 564 microm). Recurrence
      of pathology (band keratopathy and Salzmann's nodular degeneration) occurred in
      two patients. In one patient, immunohistochemical staining of corneal tissue from
      the lamellar dissection confirmed the diagnosis of herpes simplex virus type 1
      stromal keratitis, improving the course of postoperative care. CONCLUSION:
      Lamellar keratectomy with the use of an automated microkeratome is a safe and
      effective method for removing superficial anterior corneal opacities. For
      selected cases, it offers specific advantages over other surgical modalities. In
      particular, this procedure may induce far less hyperopic shift than would the
      equivalent amount of tissue removal by performing excimer laser phototherapeutic
      keratectomy.

PMID- 15260351
TI  - Accuracy and precision of EyeSys and Orbscan systems on calibrated spherical test
      surfaces.
AB  - BACKGROUND: It is important to know how well the surface topography can be
      measured with current devices for corneal topographic analysis. There are several
      applications that need an accurate and precise method to measure corneal shape
      and variations, such as the effect of contact lens wear and the different
      refractive surgery techniques. PURPOSE: The aim of this study is to compare the
      accuracy and reproducibility of the measurement of the central curvature on
      calibrated steel balls using the EyeSys videokeratoscope and the Orbscan corneal
      topography system. METHODS: The videokeratoscope (EyeSys Corneal Analysis System
      2000, version 3.1) and the Orbscan corneal topography system (Orbscan II version
      3.0) were used by four trained investigators to measure a series of five uniform
      and calibrated test surfaces with known radius of curvature ranging from 6.13 to
      9.00 mm. RESULT: No statistically significant difference was found between the
      videokeratoscope and Orbscan systems in relation to accuracy or precision. The
      95% confidence limits showed a close agreement between both instruments. The mean
      bias was less than +/-0.05 mm for both devices. The precision of the instruments
      was found to be similar. CONCLUSION: The EyeSys seems to measure more accurately,
      but the accuracy of the Orbscan was also acceptable, suggesting that both
      instruments are accurate and precise enough for research and clinical purposes.
      However, further studies of accuracy and repeatability of topographical
      measurements on human eyes generated by different topographers are necessary.

PMID- 15260352
TI  - Cataract and glaucoma after wear of contact lens soaked in steroid solution: a
      rare complication.
AB  - PURPOSE: To report an unusual case of steroid-induced cataract and glaucoma after
      wearing soft contact lens soaked in steroid solution. METHODS: Case report of a
      28-year-old man who presented with progressive decrease in vision of both the
      eyes of 2 years' duration. He was wearing conventional soft contact lens from the
      past 3 years. He used to buy the lenses from an optician and started storing the
      lenses in steroid solution overnight for the last 2 years. RESULTS: His best
      corrected visual acuity was 20/40 in both the eyes. Anterior segment evaluation
      revealed posterior subcapsular cataract in both the eyes. IOP was 12 mm of Hg in
      the right eye and 22 mm of Hg in the left eye. Fundus examination showed a cup
      disc ratio 0.9:1 in the right eye and 0.8:1 in the left eye. Humphrey visual
      fields revealed incomplete biarcuate scotoma in both the eyes. CONCLUSIONS:
      Steroid-induced cataract and glaucoma in a contact lens wearer is an extremely
      rare complication. To our knowledge, there is no previous case of steroid-induced
      cataract and glaucoma in a conventional soft contact lens wearer. This case
      emphasizes the role of optometrists and ophthalmologists in patient education
      while dispensing contact lenses, especially in developing countries.

PMID- 15260353
TI  - Sunglasses- and photochromic lens-wearing patterns in spectacle and/or contact
      lens-wearing individuals.
AB  - PURPOSE: To determine differences in wearing patterns of sunglasses and/or
      photochromic lenses in spectacle and contact lens wearers, to assess patient
      awareness of the indications for the use of tinted lenses, and to identify
      wearers' lens tint preferences. METHODS: A total of 100 individuals wearing some
      combination of contact lenses and spectacles participated in a survey
      questionnaire composed of 14 questions. Participants were asked if they used
      sunglasses/photochromic lenses, why they used them, their preferred lens tints,
      and temporal and seasonal patterns of use. They were also queried on their
      awareness of the potential adverse effects of ultraviolet radiation (UVR)
      exposure on the health of the eye and appropriate protective measures.
      Participants were categorized based on their use of spectacles and/or contact
      lenses. Demographic characteristics of sex and age were taken into account for
      the analysis. The data were imported and analyzed using commercial statistical
      analysis software. RESULTS: A total of 52% of the participants wore spectacles
      exclusively, while 48% wore some combination of spectacles and contact lenses. In
      the spectacle group, 36% and 20% wore sunglasses and photochromic lenses,
      respectively. In the contact lens group, 20% and 10% wore sunglasses and
      photochromic lenses, respectively. Overall gray was the preferred lens tint,
      especially in the younger age groups. Summer was the primary season for use of
      tinted lenses. Approximately one-third of the sample were not aware of the UVR
      protective properties of their eyewear. A total of 77% believed that UVR could be
      harmful to the eyes, but only a small percentage of the participants wore
      sunglasses or photochromic lenses specifically for UVR protection. CONCLUSION:
      There was no statistically significant difference (P = 0.07) for preference
      between sunglasses versus photochromic lenses and in seasonal patterns for tinted
      lens use among spectacles and contact lens wearers. Spectacle wearers (as well as
      contact lens wearers) used sunglasses more than photochromic lenses (P = 0.004).
      Most of the participants wore sunglasses in the summer and to protect their eyes
      from bright light. Overall gray was the preferred lens tint. Potentially adverse
      effects of UVR exposure to the eye and the importance of proper UVR eye
      protection were not generally appreciated by the subjects queried.

PMID- 15260354
TI  - Candida parapsilosis keratitis following treatment of epithelial ingrowth after
      laser in situ keratomileusis.
AB  - PURPOSE: To present a case of Candida parapsilosis following laser in situ
      keratomileusis (LASIK). METHODS: Retrospective chart review. RESULTS: A case
      report of a 51-year-old woman who underwent bilateral LASIK is presented. Two
      weeks after the procedure, the patient presented with epithelial ingrowth OD. The
      ingrowth was treated with flap lifting and scraping, followed by postoperative
      antibiotics. Four weeks later, the patient presented with numerous interface
      infiltrates. Smears were positive for yeast forms and cultures grew Candida
      parapsilosis. Administration of topical and systemic antifungal therapy resulted
      in clearing of the infection with partial visual recovery. CONCLUSIONS: To our
      knowledge, this represents the first reported case of a post-LASIK Candida
      parapsilosis keratitis. A high degree of suspicion coupled with rapid and
      appropriate treatment can result in visual recovery.

PMID- 15260355
TI  - Contact lens prescribing in a specialist medical contact lens clinic based in an
      NHS hospital: an audit of changing practice.
AB  - PURPOSE: To describe the range of indications for contact lenses and the types of
      lenses being used in an NHS hospital-based specialist medical contact lens clinic
      and contrast this with information from 12 years ago. METHODS: A retrospective
      audit of 596 clinic attendances was performed in the contact lens clinic at the
      Western Eye Hospital between April 2002 and March 2003. The results were compared
      with a similar audit performed in 1991. We used the hospitals electronic records,
      and information on contact lens prescribing was obtained directly from the
      receipts generated by the contact lens department and the accounts department.
      RESULTS: We saw 392 patients with 88.5% of patients requiring 2 or less visits
      per year. The majority of referrals are for high myopia (28.6%) closely followed
      by aphakia (25.2%) and keratoconus (24.7%). This is in contrast to 1991 when 68%
      of referrals were for aphakia and twice as many myopes (17%) were seen as
      keratoconus patients (8%). A total of 560 lenses were prescribed with 68
      different types of lens in use. The seven most commonly used lens types accounted
      for 61% of all lenses prescribed. CONCLUSIONS: Medical contact lens clinics
      provide a specialist service and also provide an important training resource for
      junior ophthalmologists. Safer cataract surgical techniques have had a
      significant impact on the case mix seen in our clinic, with the emphasis moving
      away from aphakic and myopic patients and toward the more challenging to fit eyes
      with keratoconus or postcorneal surgery.

PMID- 15260357
TI  - Subjective symptom of eye dryness and lifestyle factors with corneal
      neovascularization in contact lens wearers.
AB  - PURPOSE: To investigate effects of subjective symptom of eye dryness and
      lifestyle factors on corneal neovascularization (CNV). METHODS: Subjects were 181
      Japanese adults visiting an eye clinic for contact lens (CL) fitting. All
      completed a self-administered questionnaire related to sex, age, lens material
      (rigid gas-permeable or hydrogel lens), and subjective eye dryness. Hydrogel lens
      wearers were restricted to users of either Etafilcon A or Nelfilcon A. The
      lifestyle factors included weekly working hours on visual display terminal,
      smoking history, and duration of CL wear. CNV was graded on a 3-point ordinal
      scale using a slit-lamp and analyzed in logistic regression model: normal
      appearance (CNV 0), congestion and dilatation or vessel penetration < 1.0 mm (CNV
      1), and vessel penetration > or = 1.0 mm (CNV 2). RESULTS: The prevalence of CNV
      2 was 26% (n = 47). Multivariate analysis showed that the following three factors
      were significantly associated with CNV through the stepwise regression model: a
      use of a hydrogel lens (odds ratio [OR], 2.55; confidence interval [CI], 1.04
      6.25), subjective eye dryness (OR, 2.07; CI, 1.01-4.23), and weekly CL use (OR,
      3.08; CI, 1.14-8.00). Additionally, a positive trend was found between the degree
      of weekly CL use and the severity of CNV (P for trend test = 0.002). CONCLUSIONS:
      The prevalence of CNV in the setting of this study seemed to be higher than that
      in previous studies, indicating that a regular eye checkup is of paramount
      importance for eye care. Specifically, ocular symptomology of eye dryness with
      the information of CL use may be carefully explored in future research.

PMID- 15260356
TI  - Evaluation of the corneal effects of topical ophthalmic fluoroquinolones using in
      vivo confocal microscopy.
AB  - PURPOSE: To compare the effects of several fluoroquinolone antibiotics on the
      corneal epithelium and stroma using in vivo confocal microscopy. METHODS: Five
      antibiotic solutions were evaluated: 1) 0.3% ofloxacin (Oflox) solution with
      0.005% benzalkonium chloride (BAC); 2) 0.3% gatifloxacin (Gati) solution with
      0.005% BAC; 3) 0.3% ciprofloxacin (Cipro) solution with 0.006% BAC; 4) 0.5%
      levofloxacin (Levo) with 0.005% BAC; and 5) 0.5% moxifloxacin (Moxi) solution
      with no BAC. Preservative-free artificial tears (Tears) were used as a control.
      New Zealand white rabbits were used for this study (six per solution group). Ten
      days prior to exposure to any solution, central corneal epithelial thickness and
      stromal thickness were measured using in vivo confocal microscopy through
      focusing. Images of the superficial epithelium were also acquired. Both eyes of
      each rabbit then received one drop of the assigned solution six times the first
      day and then four times per day for 6 days. On day 7, in vivo confocal microscopy
      was repeated. RESULTS: A significant decrease in epithelial thickness was induced
      by 7 days of exposure to Levo, Gati, Oflox, and Cipro (P < 0.05, two-way repeated
      measures ANOVA, Tukey test). Tears and Moxi, which do not contain BAC, did not
      induce significant changes in epithelial thickness. No significant changes in
      stromal thickness were detected (P = 0.266), and no keratocyte activation was
      observed for any of the solutions evaluated. CONCLUSION: We have previously used
      confocal microscopy to establish a correlation between epithelial thinning (due
      to superficial cell loss) and slight ocular irritation. The results of this study
      suggest that Moxi induces less damage to the corneal epithelium than other
      antibiotic solutions, perhaps because it does not contain BAC.

PMID- 15260358
TI  - Hydrogel contact lens dehydration in controlled environmental conditions.
AB  - PURPOSE: To ascertain the impact of environmental conditions on hydrogel contact
      lens dehydration. METHODS: Six young adult subjects wore an ACUVUE lens in one
      eye and a Proclear lens in the other eye for 200 minute sessions in arid,
      temperate, and arctic conditions, maintained in a purpose-built environmental
      chamber in an aerospace medical facility. Dehydration was determined by measuring
      lens water content before and after each session using a soft contact lens
      refractometer. Comfort of the lenses was assessed at the conclusion of each
      session. RESULTS: Lens dehydration was similar for the three environmental
      conditions (F2 = 0.3, P = 0.75). There was less dehydration with the Proclear
      lens compared with ACUVUE lens (F1 = 43.0, P = 0.001). No differences were
      detected with respect to lens comfort between the three environmental conditions
      (F2 = 2.0, P = 0.18) or the two lens types (F1 = 1.4, P = 0.29). CONCLUSION: Soft
      contact lens dehydration is unaffected by environmental extremes.

PMID- 15260359
TI  - Laser in situ keratomileusis treatment for myopia after Acanthamoeba keratitis.
AB  - PURPOSE: We report a case of a patient with a history of Acanthamoeba keratitis
      in the right eye who was successfully treated with Laser in situ keratomileusis
      (LASIK) for myopia correction. METHODS: A 39-year-old woman with a history of
      wearing daily soft contact lens had early (epithelial phase) Acanthamoeba
      keratitis in the right eye. The corneal infection resolved with 5 months of
      topical polyhexamethylene biguanide and propamidine treatment. Recurrence of
      Acanthamoeba keratitis did not occur after the first episode, and no scarring of
      the cornea was noted. Laser in situ keratomileusis was performed in both eyes 2
      years later. RESULTS: The patient successfully underwent LASIK procedures in both
      eyes. No complications were observed intraoperatively and postoperatively in the
      right eye. The cornea remained clear 3 months postoperatively, and she achieved
      6/6 uncorrected visual acuity. CONCLUSIONS: Following successful treatment of
      Acanthamoeba keratitis, the LASIK procedure can be performed on previously
      infected cornea with successful results. There is no recurrence of Acanthamoeba
      keratitis at 3-month follow-up.

PMID- 15260360
TI  - Late-stage progressive corneal astigmatism after penetrating keratoplasty for
      keratoconus.
AB  - PURPOSE: Progressive corneal astigmatism occurring at least 10 years after
      penetrating keratoplasty for keratoconus is a late-phase complication of surgery.
      This report characterizes this condition in a series of patients from three
      corneal referral centers in the United States. METHODS: Charts were
      retrospectively reviewed which met the following criteria: penetrating
      keratoplasty performed for keratoconus at least 10 years ago, keratometry or
      simulated keratometry from topography as well as manifest refraction recorded at
      least 6 months after the last suture removal ("baseline"), and an increase in
      corneal astigmatism of at least three D over baseline recorded at least 5 years
      later. Patients who had any other corneal or intraocular surgery performed were
      excluded. RESULTS: Data from 15 patients (11 males and 4 females) who had
      penetrating keratoplasties performed by 8 different surgeons are included in this
      descriptive series. Postoperative follow-up averaged 17.27 years (range 11-24
      years). The average donor button size was 7.83 mm (range 7.25-8.5 mm). Baseline
      corneal astigmatism was obtained an average of 5.2 years after penetrating
      keratoplasty (range 1.5-16 years) and was on average 3.57 +/- 1.8 D (10 with-the
      rule [WTR], 3 against-the-rule [ATR], 2 oblique). Corneal astigmatism
      significantly increased to an average of 11.23 +/- 3.56 D (range 8.00-19.37 D, P
      < 0.0001) and most astigmatism was regular and WTR (9 WTR, 3 ATR, 3 oblique) 15.3
      years (range 10-22 years) after surgery. Inferior steepening on topography was
      often noted, even those with oblique and ATR axes. CONCLUSIONS: High, late-stage,
      regular astigmatism after penetrating keratoplasty for keratoconus is described
      in a series of patients occurring at least 10 years after surgery. Possible
      mechanisms of this progressive astigmatism are recurrence of keratoconus in the
      graft, progressive corneal thinning of the host cornea, or progressive
      misalignment of the graft-host interface over time.

PMID- 15260361
TI  - Recovery of corneal topography and vision following opaque-tinted contact lens
      wear.
AB  - PURPOSE: To investigate corneal changes after wearing cosmetic tinted contact
      lens and the recovery of corneal topography. METHODS: Seven subjects took part in
      the study. Three cosmetic tinted lens types and one control soft contact lens
      were investigated (Crazy Lens, WildEyes, FreshLook, and SofLens Comfort). Lenses
      were worn for 1 hour. Corneal topography data were measured before lens wear,
      with the contact lens in situ and at 0, 10, 20, 30, 60, 90, 120, and 150 minutes
      after lens removal. Height data difference maps were calculated and corneal
      recovery measured. Visual acuity was taken before lens removal and at 1, 10, 30,
      60, 120, and 150 minutes after lens removal. Subjective ratings of haloes and
      ghosting following lens wear were also recorded. RESULTS: For the Crazy Lens,
      concentric rings of steepening and flattening with a mean height change of 2.17
      +/- 0.98 microm (P < 0.05) were found in the central cornea at a location
      corresponding to the edge of the clear pupil diameter. Corneal recovery after
      removal of the Crazy Lens took up to 150 minutes. Visual acuity loss in high
      luminance during Crazy Lens wear was 0.29 LogMAR (P < 0.01). For the WildEyes and
      FreshLook lenses, smaller changes in corneal topography and vision were found
      after 1 hour of lens wear. CONCLUSIONS: Patients who wear cosmetic tinted lenses
      need to be aware of the potential for reduced visual performance, both during
      lens wear and for several hours after lens wear.

PMID- 15260362
TI  - The limbic thalamus.

PMID- 15260363
TI  - An update of the strategic plan for neuropsychiatry.

PMID- 15260364
TI  - Posttraumatic stress disorder: acquisition, recognition, course, and treatment.
AB  - Following exposure to trauma, a large number of survivors will develop acute
      symptoms of posttraumatic stress disorder (PTSD), which mostly dissipate within a
      short time. In a minority, however, these symptoms will evolve into chronic and
      persistent PTSD. A number of factors increase the likelihood of this occurring,
      including characteristic autonomic and hypothalamic-pituitary-adrenal axis
      responses. PTSD often presents with comorbid depression, or in the form of
      somatization, both of which significantly reduce the possibilities of a correct
      diagnosis and appropriate treatment. Mainstay treatments include exposure-based
      psychosocial therapy and selective serotonin reuptake inhibitors, such as
      paroxetine and sertraline, both of which have been found to be effective in PTSD.
      This paper looks at the course of PTSD, its disabling effect, its recognition and
      treatment, and considers possible new research directions.

PMID- 15260365
TI  - Absence of cortical gray matter abnormalities in psychosis of epilepsy: a voxel
      based MRI study in patients with temporal lobe epilepsy.
AB  - The authors retrospectively explored cortical differences between 26 patients
      with temporal lobe epilepsy and psychosis of epilepsy (POE), 24 patients with
      temporal lobe epilepsy (TLE) alone, and 20 healthy comparison subjects. Using
      voxel-based morphometry based on statistical parametric mapping (SPM99), which is
      an unbiased and fully automated technique to test for morphometric differences,
      magnetic resonance imaging (MRI) 3D-datasets were acquired and analyzed. There
      were no significant cortical gray matter differences between the POE and the TLE
      group. Since cortical pathology is prominent in schizophrenia, POE may be a
      clinical entity separate from schizophrenia.

PMID- 15260366
TI  - Poststroke depression and lesion location revisited.
AB  - Seventy patients with one brain infarct on magnetic resonance imaging (MRI) were
      studied 3 months after ischemic stroke by a standardized protocol to detail side,
      site, type, and extent of the brain infarct, as well as severity of white matter
      lesions and brain atrophy. Depression was diagnosed by DSM-III-R and DSM-IV
      criteria. The brain infarcts that affected structures of the frontal-subcortical
      circuits, (i.e., the pallidum and caudate, especially on the left side)
      predisposed stroke patients to depression. The size of the infarcts at these
      sites in the depressed patients was larger. Using a logistic regression analysis,
      the authors found that a brain infarct that affected pallidum was a strong
      independent MRI correlate for poststroke depression (odds ratio = 7.2).

PMID- 15260367
TI  - Dissociation, hemispheric asymmetry, and dysfunction of hemispheric interaction:
      a transcranial magnetic stimulation approach.
AB  - The authors investigated the hypothesis that dissociation may represent a
      functional dysconnectivity syndrome using a transcranial magnetic stimulation
      (TMS) approach. Transcranial magnetic stimulation investigations that included
      motor thresholds and the transcallosal conduction time (TCT) reflecting the
      interhemispheric transfer were performed in 74 right-handed students. All
      subjects completed the Dissociative Experience Scale. The high dissociators had a
      significantly lower left hemispheric excitability than right hemispheric
      excitability. They also had a significantly shorter TCT from the left to the
      right hemisphere than did the low dissociators. These results suggest that the
      neural basis of dissociation may involve a cortical asymmetry with a left
      hemispheric superiority or, alternatively, a lack of right hemispheric
      integration.

PMID- 15260368
TI  - Bilaterally reduced frontal activation during a verbal fluency task in depressed
      patients as measured by near-infrared spectroscopy.
AB  - The present study investigated functional changes of brain oxygenation in
      prefrontal brain areas of nine depressed patients and nine age- and sex-matched
      healthy comparison subjects by using near-infrared spectroscopy. During a verbal
      fluency task, the healthy subjects exhibited the typical activation pattern, with
      a significant increase in oxyhemoglobin and a decrease in deoxyhemoglobin, as
      compared to a resting baseline condition. Patients had significantly lower
      activation bilaterally during the cognitive task, with no significant differences
      in behavioral performance. The results underscore the hypothesis of a functional
      deficit in prefrontal cortex in depression and confirm the feasibility of near
      infrared spectroscopy in measuring functional brain activation.

PMID- 15260369
TI  - Cognitive impairments in cerebellar degeneration: a comparison with Huntington's
      disease.
AB  - To determine the specificity of cognitive impairments in patients with cerebellar
      degeneration (CD), the neuropsychological test performance of 31 CD patients was
      compared to that of 21 patients with Huntington's disease (HD) and 29 normal
      adults. The CD and HD groups did not differ in age, education, or duration of
      illness, and their overall severity on a quantified neurological examination was
      similar. Fifteen neuropsychological test variables were reduced to five
      underlying domains: motor, verbal, spatial, memory, and executive functioning.
      The CD patients had their greatest impairment in the executive domain and their
      least in the memory domain. In contrast, the HD patients had very substantial
      spatial deficits and significant memory impairment, in addition to executive
      dysfunction. The findings indicate that 1) the cognitive impairment in CD is not
      as severe as in HD, and 2) the pattern of deficits in CD, while consistent with a
      subcortical dementia, differs in important ways from that in HD. These
      differences may reflect the involvement of the cerebellar dentate nucleus and the
      striatal nuclei in separate "loops" or closed circuits, linking them with
      specific areas of cerebral neocortex.

PMID- 15260370
TI  - Cognitive dysfunction and depression during treatment with interferon-alpha and
      chemotherapy.
AB  - Trials with interferon-alpha (IFN-alpha) have provided contradictory findings
      regarding the presence of cognitive side effects. The development of depression
      in some patients also raises questions about whether cognitive dysfunction might
      be secondary to an organic, interferon-induced mood disorder. Thirty patients
      with chronic myelogenous leukemia were examined before and during treatment with
      IFN-alpha alone or IFN-alpha and chemotherapy. Increased depressive symptoms and
      declines in information processing and executive functions were observed, but
      depression alone could not account for cognitive dysfunction. There was some
      evidence suggesting that exposure to chemotherapy and higher cumulative IFN-alpha
      dose may contribute to cognitive impairment.

PMID- 15260371
TI  - Twenty-four-hour rhythms of sleep-wake cycle and temperature in Alzheimer's
      disease.
AB  - The authors aimed to examine the difference in 24-hour rhythms of sleep-wake
      cycle and temperature between Alzheimer's disease (AD) patients and elderly
      comparison subjects. The continuous measuring of wrist activity and skin
      temperature was conducted for 96 hours in seven AD patients (age: 77.0 +/- 4.3)
      and 11 normal comparison subjects (age: 74.2 +/-5.2). The mean acrophases and
      amplitudes of the two rhythms in the AD group were not different from those in
      the comparison group. The mean phase difference between the two rhythms, however,
      was significantly lower in the AD group than in the comparison group.

PMID- 15260372
TI  - Autism and familial major mood disorder: are they related?
AB  - Family history studies of autism consistently reveal a large subgroup with a high
      incidence of major mood disorder in family members, suggesting the two entities
      are related clinically and genetically. This review examines this concept,
      comparing current clinlical and biological knowledge of autism and major mood
      disorder, and advances the hypothesis that this subgroup of autism represents an
      early-life phenotype of major mood disorder. If confirmed, this hypothesis would
      suggest that the basic biological defects determining major mood disorders may
      have prominent neurodevelopmental and cognitive dimensions. Testing of the
      hypothesis will depend on genetic studies.

PMID- 15260373
TI  - Ottavio Pompeiano.

PMID- 15260374
TI  - Input/output properties of the lateral vestibular nucleus.
AB  - This article is a review of work in three species, squirrel monkey, cat, and rat
      studying the inputs and outputs from the lateral vestibular nucleus (LVN).
      Different electrophysiological shock paradigms were used to determine the
      synaptic inputs derived from thick to thin diameter vestibular nerve afferents.
      Angular and linear mechanical stimulations were used to activate and study the
      combined and individual contribution of inner ear organs and neck afferents. The
      spatio-temporal properties of LVN neurons in the decerebrated rat were studied in
      response to dynamic acceleration inputs using sinusoidal linear translation in
      the horizontal head plane. Outputs were evaluated using antidromic identification
      techniques and identified LVN neurons were intracellularly injected with biocytin
      and their morphology studied.

PMID- 15260375
TI  - "Critical periods" in vestibular development or adaptation of gravity sensory
      systems to altered gravitational conditions?
AB  - 1. A feature of sensory, neuronal and motor systems is the existence of a
      critical period during their development. Modification of environmental
      conditions during this specific period of life affects development in a long-term
      manner, or even irreversibly. Deprivation is the prefered approach to study the
      existence and duration of critical periods. For gravity sensory systems, space
      flights offer the only opportunity for deprivation conditions. 2. Studies in a
      fish (Oreochromis mossambicus) and an amphibian (Xenopus laevis) revealed a
      significant sensitivity of their roll-induced static vestibuloocular reflex
      (rVOR) to a 9- to 10-day gravity deprivation (microgravity) during a spaceflight.
      In some instances, the rVOR was augmented after the flight as demonstrated in
      young Oreochromis which were launched when their rVOR had not been developed, and
      in Xenopus tadpoles launched after their rVOR had developed. Fish which could
      perform the rVOR at launch were insensitive to microgravity exposure. A similar
      insensitivity to microgravity was observed in Xenopus tadpoles with normal body
      shape which had not yet developed their rVOR at launch. Some tadpoles, however,
      developed an upward bended tail during their space flight; their rVOR was
      significantly depressed after termination of microgravity independent of the age
      at onset of the flight. Hypergravity depressed the rVOR for all so far tested
      developmental stages in both Oreochromis and Xenopus. 3. Both adaptive processes
      during exposure to altered gravity as well as the existence of a critical period
      in vestibular development might be responsible for the modulation of the rVOR
      recorded after exposure to altered gravity. Deprivation studies have to be
      extended to older developmental stages to test the possibility of a critical
      period; however, this approach is limited due to the low number of space flights.

PMID- 15260376
TI  - Meta level concept versus classic reflex concept for the control of posture and
      movement.
AB  - Postural reflexes are replaced soon after birth by automatic reactions that allow
      for volition and cognition. It is still an enigma how this change in postural
      control is achieved. We suggest that the change involves the formation of a
      sensory processing level (meta level) that becomes interleaved in between the
      tight sensor-actuator coupling of the classic reflexes. We assume that the brain
      applies at this level intersensory interactions to reconstruct the physical
      stimuli which are causing the physiological stimuli and sensory signals. The thus
      derived estimates of the physical stimuli are then used as feedback signals in
      the posture control system. We present this concept on the background of the
      classic reflex concept and earlier attempts in the literature to overcome it. The
      earlier attempts were often motivated by the question how the brain prevents
      voluntary movements from being hampered by reflexive stabilisation of posture (so
      called posture-movement problem). We compare our new concept with the classic
      reflex concept in a theoretical approach, by implementing both concepts into
      simple postural control models. In simulations of the two models we superimpose
      external perturbations (the physical stimuli) and a voluntary body lean movement.
      We show that it is possible to achieve successful stimulus compensation and
      unperturbed lean movement with both, the model derived from the new concept and
      the one of the classic reflex concept. With both approaches, the posture-movement
      problem does not arise. Based on preliminary considerations that include
      experimental findings from the literature, however, we conclude that the new
      concept provides more explanatory power than the classic reflex concept.

PMID- 15260377
TI  - Coupling sensory inputs to the appropriate motor responses: new aspects of
      cerebellar function.
AB  - It is known that proprioceptive signals modify the spatial organization of the
      postural reflexes, thus leading to body stability. The neurophysiological basis
      of this phenomenon are at present unknown. The present report documents that, in
      decerebrate cat, body-to-head rotation in the horizontal plane modified the
      preferred response direction to labyrinthine stimulation of the forelimb extensor
      triceps brachii. Such direction resulted always perpendicular to the longitudinal
      body axis of the animal, whatever its relative position with respect to the head
      could be. The rotation of the preferred response direction of the triceps was
      greatly reduced by functional inactivation of the ipsilateral cerebellar vermis.
      On the other hand, following body-to-head displacement, the preferred response
      directions of the corresponding P-cells tended, on the average, to rotate in the
      same direction and by the same angle as the body. We propose that the neck input
      finely tunes parallel vestibular channels, endowed with different spatial and
      temporal properties, impinging upon P-cells, thus modifying their responses to
      animal tilt and, as a consequence, the spatial properties of VS reflexes. It is
      possible that, by a similar mechanism, the cerebellum may contribute to the
      changes in reference frame occurring in sensorimotor transformations of reflex
      and voluntary nature.

PMID- 15260378
TI  - Combined antagonism of aminergic excitatory and amino acid inhibitory receptors
      in the XII nucleus abolishes REM sleep-like depression of hypoglossal
      motoneuronal activity.
AB  - It is hypothesized that the suppression of motor activity (atonia) that occurs
      during REM sleep is caused by the combined inhibition of motoneurons by glycine
      or GABA and withdrawal of excitation mediated by serotonin and norepinephrine.
      However, it is not known whether these mechanisms can fully account for the
      atonia. In urethane-anesthetized, paralyzed and artificially ventilated rats, REM
      sleep-like episodes can be repeatedly elicited by microinjections of a
      cholinergic agonist, carbachol, into the dorsomedial pons. We used this model to
      determine whether microinjections of a combination of antagonists of
      serotonergic, adrenergic, GABA(A) and glycinergic receptors (methysergide,
      prazosin, bicuculline and strychnine) into the XII nucleus can abolish the
      carbachol-induced depression of XII motoneuronal activity. REM sleep-like
      episodes were elicited prior to, and at different times after, antagonist
      microinjections. In all six rats studied, the depression of XII motoneuronal
      activity did not occur when tested 30-60 min after the antagonists, whereas other
      characteristic features of the response (latency, duration, the appearance of
      hippocampal theta rhythm, activation of the cortical EEG, slowing of the
      respiratory rate) remained intact. The carbachol-induced depression partially
      recovered after 2-3 hours. We conclude that the REM sleep-like depression of XII
      motoneuronal activity can be fully accounted for by all or some of the following
      mechanisms: a withdrawal of motoneuronal excitation mediated by norepinephrine
      and serotonin and increased inhibition mediated by GABA and glycine.

PMID- 15260379
TI  - Trace fear conditioning: a role for context?
AB  - Fear conditioning can be rapidly obtained over long trace intervals, but its
      specificity with respect to both time and stimulus is uncertain. Long-trace fear
      conditioning often parallels contextual conditioning, and it is sensitive to
      hippocampal lesions. These properties of trace conditioning are not directly
      addressed by timing models and multiple-time-scale models of conditioning. It is
      proposed that during early stages of conditioning, a joint representation of the
      context and the stimulus trace may underlie conditioned responses, and that
      discriminative processes allow the emergence of specific responses in a later
      stage.

PMID- 15260380
TI  - Change of stretch reflex threshold in spasticity: effect of botulinum toxin
      injections.
AB  - Spasticity is a disorder of hypertonus associated with neurological diseases,
      characterized by a decrease in stretch reflex threshold. Stretch reflex threshold
      of wrist flexors has been recorded in subjects affected by forearm spasticity due
      to acute neurological lesions, occurred from one to sixty-one months before. In
      all the subjects a decreased stretch reflex threshold was recorded and a negative
      correlation between stretch reflex threshold and time of the disease resulted. In
      five subjects affected by mild spasticity the velocity stretch reflex threshold
      was tested one-three months after stroke and then six months later. In three
      cases a further decrease in stretch reflex threshold was recorded. Sixteen
      subjects affected by heavy forearm spasticity (quantified by Ashworth scale),
      were treated with Botulinum toxin injections to reduce spasticity. Fourteen of 16
      subjects were responsive to the antispastic therapy: a decrease of at least 1
      point in the Ashworth scale was detected after the treatment. In all the
      responsive cases an increase of stretch reflex threshold was recorded. The
      results confirm that the stretch reflex threshold is decreased in spastic
      muscles; it decreases progressively in time after the acute lesion. In addition,
      these results demonstrate that the decreased stretch reflex threshold can be
      reversed with Botulinum toxin injections. It is known that Botulinum toxin reduce
      the presynaptic release of Acetylcholine of neuromuscular synapses, but there are
      experimental evidences that it acts even on spindle's fibres, decreasing the
      sensitivity of intrafusal muscle fibres. This effect explains how Botulinum toxin
      increases the stretch reflex threshold in spastic muscles.

PMID- 15260381
TI  - Chronic pain as expression of neural substrates. Issues from the neuronal
      dynamics and mutual relations.
AB  - The Thalamo-Cortical somatosensory loop shows important synaptic re-organization
      in cases of chronic pain. Animal models exhibit severe functional distortions,
      potentially related to the anatomic rearrangements. Connectivity and information
      theoretic measurement represent important tools to quantify the functional
      disarrays. We performed electrophysiological experiments with multisite,
      multielectrode simultaneous recordings in the Thalamus and in the Somatosensory
      Cortex. The recurrent anomalies in the analytic estimates induce to hypothesize a
      potential neurodynamical explanation of the sensory context.

PMID- 15260382
TI  - Does hypnotizability affect human upright stance?
AB  - Subjects highly (Highs) and low susceptible to hypnosis (Lows) show different
      imagery and attentional capabilities and also peculiar somatomotor, vegetative
      and electroencephalographic differences in basal and task conditions. Since
      attention is one of the main component of hypnotic susceptibility and also a
      relevant factor for postural control, the aim of the experiment was to study
      actual differences between Highs and Lows at the eyes closure during upright
      stance. Visual and motor imagery as well as attentional/disattentional
      capabilities were evaluated through psychological tests. Posture was monitored
      though Elite systems during upright stance with open and closed eyes. At the eyes
      closure, Highs and Lows exhibited a different body sway modulation. Possible
      different compensation mechanisms are suggested for the two groups and
      interactions between attentional/arousal systems responsible of hypnotic
      phenomenology and postural control are underlined.

PMID- 15260383
TI  - An avian model of genetic reflex epilepsy.
AB  - The Fayoumi strain of chickens (Fepi) carries a recessive autosomal gene mutation
      in which homozygotes are afflicted with a photogenic and audiogenic reflex
      epilepsy. Seizures consist of stimulus-locked motor symptoms followed by
      generalized self sustained convulsions. EEG recordings show spikes and spike and
      waves patterns at rest which are suppressed during seizures and replaced by a
      desynchronized pattern of activity. Neurones of the prosencephalon discharge in
      bursts at rest, while neurones of the mesencephalon are bursting during seizures.
      Living neural chimeras were obtained by replacing specific embryonic brain
      vesicles in a normal chicken embryo with equivalent vesicles from a Fepi donor.
      These chimeras show that the epileptic phenotype can be totally or partially
      transferred from the Fepi to the normal chickens. Total transfer of photogenic
      and audiogenic seizures was obtained by substitution of both the prosencephalon
      and mesencephalon, while substitution of the prosencephalon alone resulted in
      transfer of interictal paroxysmal activity and substitution of the mesencephalon
      alone resulted principally in transfer of ictal motor symptoms. Increased
      expression of the c-fos protooncogene, as revealed by the western blot technique,
      confirmed the distinct encephalic localizations of the symptoms of the photogenic
      and audiogenic reflex epilepsy of the Fepi shown with the methods of
      electrophysiology and brain chimeras. We conclude that the Fepi is a good model
      of brain stem reflex epilepsy and suggest that the brain stem is a generator of
      some other animal and human genetic reflex "epileptic syndromes".

PMID- 15260384
TI  - Screening patients on long term non-steroidal anti-inflammatory drugs (NSAIDs)
      for nephrotoxicity--why necessary and how frequently?

PMID- 15260385
TI  - Diabetes could cost you your kidneys, act now!

PMID- 15260386
TI  - A longitudinal study of serum creatinine levels in patients of rheumatoid
      arthritis on long term NSAID therapy.
AB  - AIM: Primary: To study the effect of long term NSAID therapy on serum creatinine
      in patients of rheumatoid arthritis. Secondary: To study the effect of
      discontinuation, reduction in the dose or continuation of NSAID and of
      rechallenge. MATERIAL AND METHODS: Case records of RA patients with a minimum two
      years of follow up were analysed. Age, sex, duration of RA, type, dose and
      duration of NSAID and DMARD therapy, co-morbid conditions and serial serum
      creatinine levels were charted. RESULTS: Ninety nine case records were studied.
      Incidence of abnormal creatinine level (renal insufficiency) defined as rise in
      creatinine equal to or above the upper limit of normal was 27.7%. This rise was
      asymptomatic in all patients. No NSAID was particularly associated with an
      increased risk in renal insufficiency. The rise of serum creatinine was
      reversible in most patients irrespective of discontinuation or continuation of
      NSAID but settled at a higher level. Rechallenge resulted in rise of serum
      creatinine in 50% patients. Hypertension, DM, IHD and diuretics carried a higher
      but not statistically significant risk of renal insufficiency. CONCLUSION: NSAID
      induced asymptomatic rise of creatinine in patients of RA on long term NSAIDs is
      common. It is mostly reversible. Regular monitoring of serum creatinine is
      essential.

PMID- 15260387
TI  - A clinical and laboratory profile of Cleistanthus collinus poisoning.
AB  - AIMS: 1. To study the clinical features in patients with Cleistanthus collinus
      poisoning, 2. To study in them the effect of Cleistanthus collinus poisoning on
      the various organ systems and metabolic parameters using standard laboratory
      investigations. METHODS: All patients admitted to the hospital between September
      1998 and April 2000 were studied. Statistical analysis of the results was done
      using chi-square test, Fisher's exact test and Student's 't' test. RESULTS: Forty
      six cases were studied, 15 (32%) of whom died. Eighty percent of the patients
      were in the second to third decade. The female:male ratio was 3:2. Ingestion of
      the poison as a decoction prepared from the leaves and ingestion of a large
      number of leaves otherwise were associated with a poor outcome. While survivors
      remained relatively asymptomatic, fatally poisoned patients presented with
      significant clinical signs and symptoms, however, laboratory abnormalities such
      as hypokalaemia, hyponatremia, an elevated AST/LDH/CPK/CPK-MB, nonspecific ST-T
      changes and QTc prolongation on ECG, metabolic acidosis and hypoxia with widened
      alveolar-arterial oxygen difference (A-aDO2) were seen in both groups.
      CONCLUSION: It is a poisoning seen in the young with significant mortality. Cause
      of death appears to be mainly due to its cardiac and respiratory effects.
      Metabolic disturbances especially hypokalaemia was a prominent feature. Most
      deaths occurred on the 3rd day and all within a week. No specific antidote is
      available.

PMID- 15260388
TI  - Early human safety study of turmeric oil (Curcuma longa oil) administered orally
      in healthy volunteers.
AB  - OBJECTIVE: Turmeric extract and turmeric oil have shown chemoprotective effect
      against chemically-induced malignancies in experimental animals. They can reverse
      precancerous changes in oral submucous fibrosis in humans. The use of turmeric or
      Curcuma longa Linn as a spice and household remedy has been known to be safe for
      centuries. In view of the long term administration required for cancer prevention
      a Phase I clinical trial of turmeric oil (TO) was designed to study the safety
      and tolerance of TO in volunteers for a period of 3 months. MATERIAL AND METHODS:
      Nine healthy volunteers between 20 and 33 years of age were tested for
      haemoglobin, blood counts, liver and kidney functions, bleeding and clotting time
      and serum electrolytes initially and at 1 and 3 months of treatment. They were
      administered 0.6 ml of TO three times a day for 1 month and 1 ml in 3 divided
      doses for 2 months. The acute tolerability study on Day 1 was conducted in a
      Clinical Pharmacology daycare Unit. Blood pressure and pulse were recorded
      frequently on Day 1 and at 24, 48, 72 and 96 hours and fortnightly till 12 weeks.
      Volunteers were daily supervised for TO intake as well as for any side effects
      throughout the study period. RESULTS: Nine volunteers were enrolled for the
      study. One discontinued on 3rd day for allergic skin rashes which, on
      discontinuation of TO, gradually disappeared by two weeks. Another discontinued
      on 7th day for intercurrent fever requiring antibiotic treatment. Seven
      volunteers completed the study. There was no effect of TO, in two doses, on pulse
      and blood pressure and no side effects in acute tolerability study on Day 1.
      There was no effect of TO intake on weight, blood pressure, symptoms and signs
      upto 12 weeks. There was no clinical, haematological, renal or hepatic-toxicity
      of TO at 1 month and 3 months. Serum lipids did not show significant change
      except in one volunteer (reversible). CONCLUSIONS: In view of the potential for
      reversing oral submucous fibrosis, a precancerous condition for oral cancer, TO,
      can be recommended directly for a Phase II trial in patients.

PMID- 15260389
TI  - Beneficial effects of triple drug combination of pioglitazone with glibenclamide
      and metformin in type 2 diabetes mellitus patients on insulin therapy.
AB  - BACKGROUND: The thiazolidinediones are a class of antidiabetes medication that
      enhance the actions of insulin in muscle, liver, and adipose tissue. Data have
      been lacking on their use in combination with both sulfonylurea and metformin
      among patients of type 2 diabetes who are on insulin therapy secondary to failure
      of routine oral hypoglycemic drugs in controlling their diabetes. OBJECTIVE: To
      determine the effects of pioglitazone in combination with sulphonylurea and
      metformin on diabetes control in patients being treated with insulin due to
      secondary failure of oral hypoglycemic agents. PATIENTS: One hundred and twenty
      four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four
      centres in Mumbai, who were being treated with insulin were selected. They were
      switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg
      and pioglitazone 15 mg along with insulin. Study participants were required to
      have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they
      had any of the following: serum creatinine concentration greater than 1.5 mg/dl,
      alanine aminotransferase (ALT) level more than two times the upper limit of
      normal, symptomatic angina, cardiac insufficiency or history of myocardial
      infarction. RESULTS: Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500
      mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P <
      0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p <
      0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p <
      0.01). At 6 months, 43.35% of patients did not need to be continued on insulin.
      The total insulin requirement in 124 patients reduced by 71.81%. There were no
      significant side effects, liver enzymes were within acceptable levels, average
      weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients
      with two requiring hospitalisation, these patients were those who did not stick
      to follow-up schedules. CONCLUSIONS: With proper patient selection, pioglitazone
      with glibenclamide and metformin can be safely used in patients receiving insulin
      with good results.

PMID- 15260390
TI  - Psoriatic arthritis.
AB  - AIM OF THE STUDY: To evaluate the clinical pattern of psoriatic arthritis in
      patients attending a tertiary referral centre in South India. METHODOLOGY: Case
      records of one hundred and sixteen patients with psoriatic arthritis (PsA) who
      had attended our Rheumatology Department were analysed using demographic,
      clinical, laboratory and radiographic variables and the data were compared with
      other studies. RESULTS: Among 116 patients, 78 were males and 38 were females
      (ratio 2:1). Peak incidence (69%) was in the fourth and fifth decades. One
      patient had juvenile psoriatic arthritis (onset <16 years of age). Symmetric
      polyarthritis (48.3%) was the commonest subtype. Arthritis followed the skin
      lesions in 50.8% of patients, preceded in 12.1% and occurred simultaneously in
      37.1%. Knee (66.4%) was the commonest joint involved. Extra-articular features
      like sausage digits (19%), enthesitis (7.8%) and eye manifestations (1.7%) like
      conjunctivitis and uveitis were observed. Psoriasis vulgaris (81%) was the
      commonest psoriatic lesion. Scalp (57.8%) was the most common hidden site. All
      the three patients with DIP arthritis alone had nail lesions. ESR and C-reactive
      protein were elevated in 51.7% and 43.9% of patients respectively. Rheumatoid
      factor was positive in 3.4 % and antinuclear antibody (ANA) was present in 5.4%
      (3/56) of patients. HIV infection was detected in 2.3% (1/44) of patients.
      Radiographic features like sacroiliitis (11.2%), calcaneal spur (7.8%), erosions
      (5.2%) and syndesmophytes (5.2%) were observed. One patient had 'pencil-in-cup
      deformity'. CONCLUSION: Psoriatic arthritis is more common in males. Symmetric
      polyarthritis is the commonest subtype. Arthritis commonly follows the skin
      lesions. Psoriasis vulgaris is the most common skin lesion and scalp is the
      commonest hidden site. ESR and CRP can be normal in psoriatic arthritis.

PMID- 15260391
TI  - Malarial hepatitis.
AB  - AIMS AND OBJECTIVE: To study the clinical, biochemical and histopathological
      changes in the liver of patients of Plasmodium falciparum malaria with jaundice.
      MATERIAL AND METHOD: This study was conducted on 50 PBF confirmed cases of
      Plasmodium falciparum malaria with jaundice. Detailed history, clinical
      examination, biochemical parameters for liver function test and blood for
      hepatitis B and C was done in all patients. Liver biopsy was done for detailed
      histopathological examination in all the 20 patients having serum bilirubin
      between 3 to 10 mg%. All patients were treated by IV/oral quinine using standard
      regimen. RESULTS: Age of the patient was ranging from 15-45 years. All patients
      had jaundice, 70% had pallor, 56% had splenomegaly, 48% had hepatomegaly and 24%
      of cases had coma. Based on serum bilirubin level, the patients were categorized
      in group A (18 patients, serum bilirubin < 3 mg%), in group B (20 patients, serum
      bilirubin 3-10 mg%) and in group C (12 patients, serum bilirubin >10 mg%).
      Histopathological examination done in all the 20 patients of group B, showed
      evidence of swollen hepatocytes (100%), malarial pigment deposition (75%),
      inflammatory infiltrates (60%), congestion of hepatocyte (50%) alongwith
      centrizonal necrosis in 25% of cases. CONCLUSION: The evidence of predominant
      conjugated hyperbilirubinemia, increased levels of AST and ALT along with
      evidence of hepatocellular necrosis in histopathological examination are strong
      evidence of gross hepatocytic dysfunction in patients of Plasmodium falciparum
      malaria with jaundice. Therefore the term malarial hepatitis should not be taken
      as a misnomer.

PMID- 15260392
TI  - Transmission of malaria and its control in the northeastern region of India.
AB  - Let alone the eradication, malaria control itself has amounted to be a challenge,
      and is detrimental to the all round development of the northeastern region of
      India. Focal outbreaks are frequent taking heavy tool on human lives. Plasmodium
      falciparum is the predominant parasite species and is solely responsible for
      increased morbidity and mortality. The region contributes bulk of P. falciparum
      cases for the rest of India, and its proportions are increasing. Efficient
      vectors like Anopheles minimus, Anopheles fluviatilis and Anopheles dirus
      persistently support transmission of malaria. The present review gives a
      comprehensive account of the factors responsible for transmission of the disease
      with focus on vector bionomics, its prevention and control.

PMID- 15260393
TI  - Prayer sign. Diabetic cheiroarthropathy.

PMID- 15260394
TI  - HIV-associated dementia and caudate atrophy.

PMID- 15260395
TI  - Diabetes in old age: an emerging epidemic.
AB  - Diabetes in the elderly is emerging as one of the most important public health
      problems of the 21st century. In developing countries, the majority of people
      with diabetes are in the age range of 45-64 years. A better understanding on the
      pathogenesis of diabetes in the aging population is required to successfully
      treat and prevent its devastating complications. Changes in body composition with
      accumulation of fat in the abdomen is a key factor in the causation of diabetes
      in the aging population. The size and strength of skeletal muscle, a major tissue
      involved in glucose metabolism, also declines leading to muscle weakness and a
      reduction in physical activity. These changes lead to marked reduction in energy
      expenditure and abdominal fat accumulation causing insulin resistance. Recent
      evidence suggests that four months of aerobic exercise can improve muscle
      oxidative capacity similarly in younger and older people, but that insulin
      sensitivity is less likely to improve in older people. It appears that older
      people need to exercise more frequently to improve their insulin sensitivity.
      Diagnosis and management of diabetes in the elderly requires special attention
      since age, genetics, body composition and lifestyle factors all interact.
      Increasing evidence suggests that postprandial hyperglycemia is more sensitive to
      diagnose diabetes in elderly people than in the young. Age related changes in
      body function and cognition demand special caution in the selection of
      hypoglycemic drugs in the elderly. Targets of diabetes therapy in the elderly
      have to be individualized, considering the age of the patient, remaining life
      expectancy and severity of co-morbid conditions. Short acting insulin
      secretogogues are preferred to avoid prolonged and frequent hypoglycemia.
      Judicious choice of insulin sensitizers, timely introduction of insulin,
      meticulous control of hypertension and hyperlipidemia are critical to prevent
      complications.

PMID- 15260396
TI  - Vertigo and dizziness--a clinical approach.
AB  - Dizziness is a term which is used to describe a variety of sensations. It is
      possible to group these complaints into four types: a rotational sensation (Type
      I dizziness), impending faint (Type II dizziness), dysequilibrium (Type III
      dizziness) and vague lightheadness (Type IV dizziness). Type I dizziness or
      vertigo is due to disease of the vestibular system--peripheral or central, and is
      characterized by a feeling of movement relative to one's surrounding. The
      majority of dizzy patients, however, belong to Types II, III and IV, collectively
      called the non-vestibular system disorders. The distinction is usually possible
      by a detailed history and clinical examination, but some special bedside tests-
      the dizziness simulation battery--are often required for properly distinguishing
      the various types of dizziness. Important causes of vertigo and the non
      vestibular system disorders have been discussed with focus on benign positional
      vertigo, acute peripheral vestibulopathy, Menieres' disease, toxic damage to
      labyrinths, perilymph fistula, cerebrovascular disease, multiple sclerosis,
      cerebellopontine angle tumors, basilar migraine, vestibular epilepsy, cervical
      vertigo and phobic postural vertigo.

PMID- 15260397
TI  - Human immunodeficiency virus infection in a patient with systemic lupus
      erythematosus.
AB  - We describe a 47 years lady with systemic lupus erythematosus (SLE) who was
      infected with human immunodeficiency virus (HIV), due to transfusion either by
      blood or platelet concentrate. There was a near remission in the disease and
      during the course of follow up she developed cryptococcal meningitis. The
      approach to the diagnosis of HIV infection in a patient with SLE, the effect of
      SLE on the virus and vice versa and some management issues in this setting are
      discussed.

PMID- 15260398
TI  - Relapsing polychondritis in an elderly male.
AB  - A 65 years patient presented with left ear swelling, swelling of the nasal bridge
      with congestion of the eyes. Clinically there was evidence of left auricular
      chondritis, nasal chondritis and conjunctivitis with a history of multiple
      similar episodes in the past, features suggestive of relapsing polychondritis.
      The patient improved with oral prednisolone.

PMID- 15260399
TI  - Cerebral sparganosis.
AB  - A 22 years male patient presented with recurrent seizures, CT and MRI diagnosis
      of tuberculoma was made and the patient was treated. When seizures persisted, a
      craniotomy was done and the excised mass revealed an abscess with a segment of
      broad solid non-cavitory body, wall with no scolex and loose stroma and smooth
      muscle fibers. A diagnosis of sparganosis cerebral abscess was made. The case is
      reported in view of the rarity of cerebral sparganosis in India and the need for
      awareness of the entity in India.

PMID- 15260400
TI  - Gerhard Armauer Hansen (1814-1912) postal stamps released in France, Norway
      (1973), in India at 12th Int. Leprosy Congress, Delhi 1984.

PMID- 15260401
TI  - Late-onset polymyositis in a case of poikilodermatomyositis.
AB  - A case of poikiloderma developed polymyositis ten years after the onset of skin
      changes. This rare case of poikilodermatomyositis, hitherto not reported from
      Asian continent, is documented.

PMID- 15260402
TI  - Distal spinal muscular atrophy.
AB  - Spinal muscular atrophies (SMA) are clinically heterogenous group of motor system
      disorders characterised by progressive pure lower motor neuron involvement. The
      distal form of SMA is an extremely rare disorder, which presents in the adults
      and has a relatively slow progression with almost no effect on the patients' life
      span. Differential diagnosis of this syndrome include other forms of
      neuromuscular disorders with peroneal muscular atrophy like hereditary motor
      sensory neuropathy (HMSN) and distal myopathies, which need exclusion before
      confirming this rare entity. We present a young male with this disorder and
      briefly discuss the theoretical aspects.

PMID- 15260403
TI  - Primary orbital lymphoma.
AB  - Primary orbital lymphoma is a rare condition involving primarily the lacrimal
      glands. We present the second Indian case of right-sided primary orbital lymphoma
      in an elderly male who presented with the typical features and showed a good
      response to chemotherapy.

PMID- 15260404
TI  - Chronic thromboembolic pulmonary hypertension--diagnosed on spiral CT
      angiography.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a part of the spectrum
      of venous thromboembolism in which pulmonary thrombus fails to resolve, resulting
      in occlusion of the major pulmonary artery. Diagnosis of this disease is
      important as it is potentially curable by pulmonary thromboendarterectomy. A case
      of CTEPH diagnosed non-invasively on spiral computerized (CT) pulmonary
      angiography is reported.

PMID- 15260405
TI  - Physician! Heal thyself.

PMID- 15260406
TI  - Brucellosis as a cause of prolonged fever in an era of pasteurized milk.

PMID- 15260407
TI  - A case of sensory Guillain Barre' syndrome.

PMID- 15260408
TI  - New frontiers of therapy in hemato-oncology.

PMID- 15260409
TI  - Quality of life in type 2 diabetes.

PMID- 15260410
TI  - Is sildenafil safe with alcohol?

PMID- 15260411
TI  - Inverted biceps jerk.

PMID- 15260412
TI  - Surgical treatment of femoral fractures in children. Comparison between external
      fixation and elastic intramedullary nails: a review.
AB  - Femoral fractures represent about 2% of all fractures in childhood. Children with
      femoral fractures always need to be admitted to hospital and the use of resources
      is much higher than for other childhood fractures. During the past decade, there
      has been a trend towards surgical treatment of these fractures, one advantage
      being the shorter time required in hospital. Two common surgical treatment
      options are external fixation (EF) and elastic stable intramedullary nails
      (ESIN). Both methods have their advantages and disadvantages, and neither of them
      solves all of the problems. Used in a complementary manner, they are safe and
      reliable for the treatment of femoral fractures in children, and they give good
      long-term results and few serious complications.

PMID- 15260413
TI  - A cost analysis of three methods of treating femoral shaft fractures in children:
      a comparison of traction in hospital, traction in hospital/home and external
      fixation.
AB  - INTRODUCTION: There is no consensus as to which is best treatment of femoral
      fractures in children. PATIENTS AND METHODS: We performed a cost analysis
      comparing three treatments of femoral shaft fractures in children aged 3-15 years
      at 3 hospitals during the same period (1993-2000). The analysis included total
      medical costs and costs for the care provider and were calculated from the time
      of injury up to 1 year. RESULTS: At hospital 1, treatment consisted of external
      fixation and early mobilization. At hospital 2, the treatment was skin or
      skeletal traction in hospital for 1-2 weeks, followed by home traction. At
      hospital 3, treatment was skin or skeletal traction in hospital until the
      fracture healed. RESULTS: The average total costs per patient were EUR 10,000 at
      hospital 1, EUR 23,000 at hospital 2, and EUR 38,000 at hospital 3.
      INTERPRETATION: The main factor for determining the cost of treatment was the
      number of days in hospital, which was lower in children treated with external
      fixation.

PMID- 15260414
TI  - Femoral shaft fractures in children: elastic stable intramedullary nailing in 31
      cases.
AB  - We report our experience with elastic stable intramedullary titanium nailing
      (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31
      children (20 boys), median age 6 (4-11) years, with ESIN for 29 closed and 2
      grade I open femoral shaft fractures. We reviewed 30 children clinically after
      median 1.5 (1-3) years. Their median hospital stay was 6 (2-20) days. All
      fractures were radiographically united at a median of 7 (5-9) weeks. The nails
      were removed in 29 children after a median of 22 (6-38) weeks postoperatively. At
      follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10
      degrees of internal rotational deformity in 1 child. No angular deformity had
      occurred. Elastic stable intramedullary nailing seems to be a safe method for the
      treatment of femoral shaft fractures in children between 4 and 11 years of age.

PMID- 15260416
TI  - Low accuracy of stem implantation in THR using the CASPAR-system: anteversion
      measurements in 10 hips.
AB  - We studied 10 patients by means of pre- and postoperative CT who underwent
      computer-assisted total hip replacement using the CASPAR-system (OrthoMaquet
      GmbH, Rastatt, Germany). The anteversion angles of the stem and translational
      deviations measured after surgery were compared to the preoperatively planned
      ones as a quality control. We found an average difference of 7.8 degrees (SD 6.3
      degrees; 95% CI 3.3 degrees-12.3 degrees) in the angles and an average difference
      of 1.8 (SD 1.7; 95% CI 0.6-3.0) mm and 1.2 (SD 1.4: 95% CI 0.25-2.2),
      respectively, in the medial and lateral deviation. In conclusion, we could not
      confirm the same accuracy of implant position as that claimed by the
      manufacturer.

PMID- 15260415
TI  - A new CT method for measuring cup orientation after total hip arthroplasty: a
      study of 10 patients.
AB  - BACKGROUND: It is difficult to assess the orientation of the acetabular component
      on routine radiographs. We present a method for determining the spatial
      orientation of the acetabular component after total hip arthroplasty (THA) using
      computed tomography. PATIENTS AND METHODS: Two CT-scans, 10 min apart, were
      obtained from each of 10 patients after THA. Using locally developed software,
      two independent examiners measured the orientation of the acetabular component in
      relation to the pelvis. The measurements were repeated after one week. To be
      independent of the patient position during scanning, the method involved two
      steps. Firstly, a 3D volumetric image of the pelvis was brought into a standard
      pelvic orientation, then the orientation of the acetabular component was
      measured. The orientation of the acetabular component was expressed as operative
      anteversion and inclination relative to an internal pelvic reference coordinate
      system. To evaluate precision, we compared measurements across pairs of CT
      volumes between observers and trials. RESULTS: Mean absolute interobserver angle
      error was 2.3 degrees for anteversion (range 0-6.6 degrees), and 1.1 degrees for
      inclination (range 0-4.6 degrees). For interobserver measurements, the precision,
      defined as one standard deviation, was 2.9 degrees for anteversion, and 1.5
      degrees for inclination. A Student's t-test showed that the overall differences
      between the examiners, trials, and cases were not significant. Data were normally
      distributed and were not dependent on examiner or trial. INTERPRETATION: We
      conclude that the implant angles of the acetabular component in relation to the
      pelvis could be detected repeatedly using CT, independently of patient
      positioning.

PMID- 15260417
TI  - No benefits with computer assistance in triple pelvic osteotomy.
AB  - We evaluated computer-assisted surgery (CAS) used for 21 triple pelvic
      osteotomies on 20 patients with symptomatic acetabular dysplasia and compared the
      intraoperative and immediate postoperative data with those of 32 patients who
      underwent 40 pelvic osteotomies without CAS. The use of the CAS system was
      abandoned during 9/21 operations mostly because of technical and CT data failure.
      The peroperative blood loss and duration of surgery were greater, while
      neurovascular damage occurred less often in the CAS group. We found that the CAS
      system for pelvic osteotomy was not better than conventional methods.

PMID- 15260418
TI  - Acetabular cementing technique in THA--flanged versus unflanged cups, cadaver
      experiments.
AB  - BACKGROUND: There are few studies on the effect of acetabular cup design on
      cement penetration. MATERIAL AND METHODS: We evaluated the effects of an
      acetabular flange on cement pressurization and cement penetration in 12 cadavers.
      Flanged or unflanged cups were implanted in paired human acetabula with simulated
      intraosseous bleeding pressure but without cement pressurization before insertion
      of the cup. Three pressure transducers were used to record intra-acetabular peak
      and average pressures during cup insertion. Following implantation, the whole
      specimens were AP-radiographed and standardized sections through the acetabula
      were microradiographed to evaluate cement penetration. RESULTS: Flanged cups
      produced greater intra-acetabular peak pressures than unflanged cups, but did not
      increase the average intra-acetabular pressure. Cement penetration did not differ
      significantly between the two groups. INTERPRETATION: Our findings do not support
      the use of flanged cups as the sole means of cement pressurization in the
      acetabulum.

PMID- 15260419
TI  - High osteolysis and revision rate with the hydroxyapatite-coated ABG hip
      prostheses: 65 hips in 56 young patients followed for 5-9 years.
AB  - BACKGROUND: There are few reports on the outcome of uncemented HA-coated cups in
      young patients. PATIENTS: I evaluated the 7-year (5-9) results of HA-coated hip
      prosthesis (ABG, Stryker) in a consecutive series of 65 primary arthroplasties on
      56 patients (mean age 44 years). 2 patients were lost to follow-up and 3 died.
      RESULTS: The cumulative survival rate with revision for any reason as endpoint at
      9 years was 98% (95% CI, 96-100) for the stem, 69% (61-77) for the acetabular
      metal backing, and 59% (50-67) for the polyethylene liner. 15 of 65 cups were
      revised on average 6 years after the primary operation and 3 more are planned.
      Revisions were done in 3 hips because of loosening and migration of the cup, and
      in 12 hips because of wear and progressive osteolysis around stable components.
      Only hips with migration had clinical symptoms. Visual inspection of polyethylene
      liners revealed wear of the articulation in all cases, loosening of the locking
      mechanism in 10 cases and nonarticular surface deformity in 7 hips. All original
      stems are in situ although femoral osteolysis was seen in 12 cases and 1 hip was
      reoperated because of periprosthetic traumatic fracture. Despite the high
      revision rate, the clinical improvement was good: the average pre- and
      postoperative Harris Hip Scores at the most recent follow-up were 41 and 90,
      respectively. INTERPRETATION: While the results on the femoral side were good,
      the survival rates of the acetabular cups were poor and we stopped using ABG I
      hip prostheses.

PMID- 15260420
TI  - Catastrophic failure of an uncemented acetabular component due to high wear and
      osteolysis: an analysis of 154 omnifit prostheses with mean 6-year follow-up.
AB  - BACKGROUND: The purposes of this study were (1) to evaluate the wear pattern of
      the hydroxyapatite-coated "Dual Radius" Omnifit cup, (2) to investigate whether
      wear is correlated to any demographic or prosthesis-related factors, and (3) to
      describe micromotion of both the cup and the stem. PATIENTS AND METHODS: 154 hips
      were implanted between 1990 and 1996 and followed for an average of 6 years. Wear
      was measured according to the "Charnley-duo" method and, in 79 hips, with
      radiostereometry IRSA). RSA was also used to evaluate micromotion. We analyzed
      the femoral heads using scanning electron microscopy, energy dispersive X-ray
      spectroscopy and an atomic force microscope. RESULT: 66 cups were revised and had
      a mean annual wear of 0.32 mm compared to 0.12 mm in hips not revised. Osteolytic
      processes were observed in 35 hips but at revision osteolysis was present in 51
      cases. 43/66 sockets were loose. Micromotion evaluated by RSA, weight, age, side,
      size of cup, screws, polyethylene thickness or shelf-life of the polyethylene did
      not correlate to wear, whereas male gender did. INTERPRETATION: It is still
      unclear why about half of our cases had an abnormal wear rate. Annual wear
      exceeding 0.2 mm is prognostic of late failure and should be considered a warning
      sign.

PMID- 15260421
TI  - Effects of polyethylene and TiAlV wear particles on expression of RANK, RANKL and
      OPG mRNA.
AB  - BACKGROUND: Wear debris has been associated with periprosthetic osteolysis and
      loosening of total joint arthroplasties. RANKL (receptor activator of NF-kappaB
      ligand), RANK (receptor activator of NF-kappaB) and OPG (osteoprotegerin) are
      three key molecules which regulate differentiation, survival, fusion, and
      activation of osteoclasts. MATERIAL AND METHODS: We evaluated the effect of TiAIV
      and polyethylene particles on expression of RANK, RANKL and OPG mRNA. We used a
      human monocytic leukemic cell line (THP-1) in this in vitro study. THP-1
      monocytes were differentiated into macrophage-like cells and exposed to
      polyethylene particles and prosthesis-derived TiAIV particles. The supernantant
      was used for measurement of TNFalpha protein and total RNA was extracted from the
      cells. Expression of the genes coding for OPG, RANKL and RANK was analysed at the
      mRNA level using a semiquantitative RT-PCR method. RESULTS: Both polyethylene and
      TiAIV particles induced a significant release of TNFalpha after 6 h of exposure
      and a significant upregulation of RANK mRNA. OPG mRNA expression was transiently
      upregulated after exposure to polyethylene and TiAIV particles. These effects
      were dependent on particle dose. RANKL mRNA was not detectable in our THP-1
      model. In contrast, LPS exhibited a different pattern of RANK/ RANKL/OPG mRNA
      expression. INTERPRETATION: Our findings provide evidence that both polyethylene
      and TiAIV particles induce upregulation of RANK expression in cells of the
      monocytic lineage, which may be important for periprosthetic osteoclastogenesis.

PMID- 15260422
TI  - Neck fracture femoral heads for impaction bone grafting: evolution of stiffness
      and compactness during impaction of osteoarthrotic and neck-fracture femoral
      heads.
AB  - BACKGROUND: The need for safe bone allografts is increasing and preservation of
      femoral heads from patients being operated on with hip arthroplasty should be
      encouraged. However, should we preserve femoral heads from patients operated on
      for neck fracture as tissue mechanical quality may not be satisfactory? MATERIAL
      AND METHODS: We compared the evolution of stiffness and compactness of fresh
      frozen morselized bone obtained from osteoarthrotic femoral heads and those from
      neck fractures. Both materials were also compared after freeze-drying and
      irradiation. We used 6 osteoarthrotic and 6 neck-fracture femoral heads to
      prepare 4 batches of morselized bone. 18 samples from each batch were impacted in
      a contained cylinder. Frozen bone grafts were tested after thawing at room
      temperature for 2 hours and freeze-dried grafts were tested after 30 minutes of
      rehydration. RESULTS: The stiffness of fresh-frozen neck fracture bone was lower
      than that of fresh-frozen osteoarthrotic bone at 150 impactions. The stiffness of
      freeze-dried irradiated bone was higher than that of the fresh-frozen bone and
      did not differ between osteoarthrotic and neck-fracture bone. INTERPRETATION:
      Solvent-treated freeze-dried bone from femoral heads procured during arthroplasty
      for sub-capital hip fractures represents a valuable source of material for
      allografts, addressing concerns regarding serological testing, medical history
      and bone quality.

PMID- 15260423
TI  - Freeze-dried irradiated bone brittleness improves compactness in an impaction
      bone grafting model.
AB  - BACKGROUND: Defatted bone chips with or without freeze-drying and irradiation
      have mechanical advantages as compared to fresh-frozen controls in in vitro
      models of impaction. These improved results have been ascribed to replacement of
      viscous bone marrow by saline and embrittlement of the freeze-dried bone by
      irradiation. MATERIAL AND METHODS: To determine which of these hypotheses is
      correct, we compared the development of stiffness and compactness of morselized
      bone graft that had been: 1) fat-reduced with saline, and 2) fresh-frozen,
      solvent-detergent defatted, 3) freeze-dried irradiated and 4) not irradiated. We
      used 12 osteoarthrotic femoral heads to prepare these four batches of morselized
      bone, and impacted 18 samples from each batch in a cylinder. The frozen bone
      grafts were tested after thawing at room temperature for 2 hours and the freeze
      dried grafts were tested after 30 minutes of rehydration. We monitored the
      development of compactness and stiffness of the material during impaction.
      RESULTS: The stiffness of the freeze-dried irradiated bone was greater than that
      of the other three series after 10, 50 and 150 impactions. The freeze-dried bone
      chips that were not irradiated and the chips defatted with saline alone were less
      stiff than the fresh-frozen control after 150 impactions. INTERPRETATION: The
      brittleness of freeze-dried irradiated bone, caused by loss of the capacity to
      absorb energy in a plastic way, increases the compactness and stiffness of the
      morselized grafts. Washing bone with saline alone or treating bone with solvent
      detergent but no irradiation had no similar mechanical advantage and the bone did
      not impact better than fresh-frozen undefatted bone in our model.

PMID- 15260424
TI  - Standing radiographs underestimate joint width: comparison before and after
      resection of the joint in 34 total knee arthroplasties.
AB  - BACKGROUND: Measurement or estimation of joint width is routinely used in the
      preoperative evaluation of gonarthrosis. To our knowledge, the validity and
      reproducibility of this procedure has not been adequately studied. PATIENTS AND
      METHODS: We measured joint width in 34 knees (medial arthrosis: n = 22, lateral
      arthrosis: n = 12) on preoperative weight-bearing radiographs and on radiographs
      of the corresponding part of the joint after knee arthroplasty. The
      bone/cartilage pieces were placed in anatomical positions and loaded in a jig
      made of perspex. High-density film was used to obtain maximum resolution.
      RESULTS: In medial and lateral arthrosis, the minimum joint widths were median
      0.3 and 0.2 mm smaller on the radiographs of the specimens (p = 0.05, 0.04). In
      lateral arthrosis the differences were more scattered (95% CI: lateral: 0.1 to 
      1.2 mm; medial: 0 to -0.5 mm), suggesting less precise determination.
      INTERPRETATION: In medial arthrosis, the degree of underestimation is usually
      small and acceptable. More pronounced discrepancies could be found in lateral
      arthrosis, calling for the use of further diagnostic measures.

PMID- 15260425
TI  - Magnetic reasonance imaging of the surgically repaired meniscus: a 13-year follow
      up study of 13 knees.
AB  - BACKGROUND: This study was initiated to evaluate the long-term outcome of
      meniscal sutures and to correlate clinical findings with MRI findings. We were
      interested to see if a clinically healed meniscus also showed as such on MRI and
      if degenerative changes were present PATIENTS AND METHODS: We studied
      prospectively 13 patients (7 men) aged between 29 and 50 years, who had undergone
      closed meniscus repair between 1985 and 1988 using an inside-out technique,
      clinically and with MRI, with a mean follow-up time of 13 years. RESULTS:
      Meniscal suture gave good clinical long-term results: all patients got a Hospital
      for Special Surgery score of more than 75%. In all patients the site of the
      previous suture was still visible on MRI, mainly from small metal artefacts in
      the meniscus. 4 of 7 patients with an unrepaired ACL lesion had signs of
      arthrosis and cartilage degeneration. MRI showed signs of mucoid degeneration or
      scar tissue in 6/13 of the patients. INTERPRETATION: We believe that asymptomatic
      meniscal tears produce abnormal MR signals even though they have stable unions,
      and that MR signals at the site of repair represent edematous scar tissue, not
      true nonunions.

PMID- 15260426
TI  - The need for education in evidence-based orthopedics: an international survey of
      AO course participants.
AB  - BACKGROUND: As evidence-based practitioners, surgeons need to understand study
      methodology to critically appraise and conduct research. OBJECTIVE: To determine
      current understanding of study methodology and critical appraisal among
      participants at an international educational meeting. METHODS: We surveyed
      participants attending the 76th and 77th AO Course (December 2002) in Davos,
      Switzerland. We obtained information regarding participant age, gender, clinical
      and research experience, subspecialty area and respondents' roles in the AO
      course. The survey questions were formatted into three areas: evidence-based
      orthopedics, randomization and blinding issues. RESULTS: 532 participants
      completed the questionnaire. They represented 78 countries, the majority of which
      (31%) were from German-speaking countries. A greater proportion of participants
      trusted randomized controlled trials (89%) and meta-analyses of randomized trials
      (81%) when compared with case series and case reports. 60 respondents (11%) had
      never heard of the term "randomization" as a study design method to limit bias,
      and 114 respondents (21%) had never heard of the term "blinding" as a method of
      reducing bias in surgical research. When those who had heard of blinding were
      asked to define the term "double-blind", 20 different definitions resulted.
      Having completed the survey, nine-tenths of the respondents endorsed the need for
      training of surgeons in research methodology.

PMID- 15260427
TI  - The impact of time of admission on major complications and mortality in patients
      undergoing emergency trauma surgery.
AB  - BACKGROUND: Previous studies have shown a relationship between time of admission
      to hospital and mortality rates; however, it is uncertain whether such a
      relationship exists for patients requiring emergency trauma surgery. METHODS: We
      included all trauma patients, except those with moderate to severe burns, who
      presented to a university-affiliated level 1 trauma center and underwent surgery,
      from 1995 until 2001 (n = 1044). We conducted univariate and multivariate
      analyses in which the dependent variables were in-hospital mortality and major
      complications, and the independent variables were the time of presentation to the
      trauma centre (nighttime vs. daytime, weekend vs. weekday, month of year, and
      year), age, sex, injury severity score, type of operative procedure, and total
      number of operative procedures. RESULTS: None of the factors related to time of
      presentation were associated with major complications or mortality. Factors
      predictive of increased mortality were higher ISS (odds ratio 1.07; 95%
      confidence interval 1.03-1.08), older age (1.04; 1.03-1.07), operations involving
      the cardiovascular system (1.7; 1-2.6), "miscellaneous" operative procedures
      (1.8; 1.1-2.9), and major complications (2.4; 1.4-4.2). INTERPRETATION: Time of
      presentation for emergency trauma surgery was not associated with differences in
      major complications or in mortality.

PMID- 15260428
TI  - High local concentrations without systemic adverse effects after impaction of
      netilmicin-impregnated bone.
AB  - BACKGROUND: When cancellous bone is impregnated with antibiotics the subsequent
      release of antibiotics from the bone shows a high early release. Hence, impaction
      of large amounts of netilmicin-impregnated bone may cause toxic netilmicin values
      in serum. PATIENTS AND METHODS: We studied kidney and otovestibular function
      after impacting 50 g of netilmicin-impregnated cancellous bone during revision
      hip or knee arthroplasty in 20 patients. The bone was impacted in the acetabulum
      (n = 8), proximal femur (n = 9) and distal femur/proximal tibia (n = 3). Serum
      creatinine concentration was measured and audiometry was performed before and
      after the operation. Netilmicin concentrations in serum, joint fluid, and in
      urine were recorded postoperatively at regular intervals. We analyzed
      pharmacokinetics in two study groups receiving bone impregnated with netilmicin
      (50 mL), at either 50 mg netilmicin/mL (group I) or 100 mg netilmicin/mL (group
      II). RESULTS: Neither netilmicin-induced renal toxicity, nor otovestibular
      toxicity was registered. Peak serum netilmicin values in group I and group II
      were 0.9 (0.5-1.3) mg/L and 1.8 (0.6-4.0) mg/L, respectively (p = 0.04). Peak
      netilmicin concentrations in wound drainage fluid in group I and group II were
      237 (9-647) mg/L and 561 (196-1132) mg/L, respectively (p = 0.01). In both
      groups, netilmicin was recovered in urine samples for approximately 4 weeks.
      INTERPRETATION: 50 grams of cancellous bone impregnated with 100 mg/mL netilmicin
      solution was impacted in the hip or knee joint with no adverse effects. Extremely
      high local concentrations of netilmicin in joint fluid were recorded
      postoperatively. The use of antibioitic-impregnated cancellous could be an option
      when performing revision of hip and knee prostheses.

PMID- 15260429
TI  - Cigarette smoking delays bone healing: a prospective study of 200 patients
      operated on by the hemicallotasis technique.
AB  - BACKGROUND: Cigarette smoking is known to impede bone healing. The hemicallotasis
      technique is based on an external fixation and delayed healing prolongs treatment
      and increases the risk of further complications. PATIENTS AND METHODS: 200
      patients, 34 smokers and 166 nonsmokers, operated on by the hemicallotasis
      technique in the proximal tibia for deformities of the knee (knee arthrosis in
      186 patients) were consecutively studied. We recorded their preoperative smoking
      habits, postoperative complications and the duration of treatment with external
      fixation. RESULTS: Half of the smokers and one fifth of the nonsmokers developed
      complications. Their mean time in external fixation was 96 (SD 20) days. Smokers
      required an average of 16 days more in external fixation. Delayed healing and
      pseudoarthrosis were commoner in smokers than nonsmokers. The risk ratio for
      smokers to develop complications was 2.5, as compared to nonsmokers.

PMID- 15260430
TI  - Intravenous regional administration of corticosteroids in juvenile chronic
      arthritis.
AB  - BACKGROUND: Treatment of juvenile chronic arthritis patients with longstanding
      multiple joint or tendon involvement that is resistant to medication remains a
      challenge. For 20 years, we have been treating these severely ill patients with
      intravenous regional glucocorticoids (a modified Bier's block). PATIENTS AND
      METHODS: Since 1996, all juvenile chronic arthritis patients have been followed
      prospectively by an occupational therapist who has registered the grip strength
      and range of motion at an average of 6 months after treatment. RESULTS: In 22/40
      wrists and hands, increased grip strength was recorded. The mean grip strength
      increased for the whole group from 47 to 59 N and the flexion lag decreased.
      INTERPRETATION: The effect of intravenous regional steroid treatment may be
      limited from a long-term perspective, but in our series, half of the patients
      showed a considerable improvement after 6 months. Surgical synovectomy can be
      postponed and perhaps even be omitted.

PMID- 15260431
TI  - Arthroplasty for ochronotic arthritis: no failure of 11 replacements in 3
      patients followed 6-12 years.
AB  - BACKGROUND: Alkaptonuria is a rare single-gene disorder characterized by black
      pigmentation of cartilage and other connective tissues. Premature degenerative
      arthritis affects the large joints in many of these of patients. Medical
      treatment is limited to a protein-restricted diet (phenylalanine and tyrosine)
      with surgery reserved for end-stage joint disease. As in other metabolic bone
      diseases, there are concerns about the quality and strength of affected bones and
      therefore the suitability and longevity of replacement arthroplasty. The
      histopathology and outcome of joint replacement for alkaptonuric arthritis is
      unknown and limited to sporadic case reports. PATIENTS AND RESULTS: We describe
      11 joint replacements in 3 patients with alkaptonuric polyarthropathy, including
      shoulder and elbow replacements not previously reported. No prosthetic failures
      occurred in up to 12 years of follow-up. INTERPRETATION: Total joint replacement
      is an acceptable treatment for degenerative joint disease in alkaptonuric
      patients, with implant survival comparable to that found in patients with
      osteoarthritis.

PMID- 15260432
TI  - Potential role of pre-existing blood vessels for vascularization and
      mineralization of osteochondral grafts: an intravital microscopic study in mice.
AB  - BACKGROUND: The aim of this study was to develop an experimental model that
      allows to elude the potential role of the preexisting graft microvasculature for
      vascularization and mineralization of osteochondral grafts. ANIMALS AND METHODS:
      For that purpose, the II-IV metatarsals of fetal DDY-mice known to be
      nonvascularized at day 16 of gestation (M16) but vascularized at day 18 (M18)
      were freshly transplanted into dorsal skin fold chambers of adult DDY mice. Using
      intravital microscopy angiogenesis, leukocyte-endothelium interaction and
      mineralization were assessed for 12 days. RESULTS: Angiogenesis occurred at 32
      hours in M18, but not before 57 hours in M16 (p = 0.002), with perfusion of these
      vessels at 42 hours (p = 0.005) and 65 hours (p = 0.1), respectively. Vessels
      reached a density three times as high as that of the recipient site at day 6,
      remaining constant until day 12 in M18, whereas in M16 vascular density increased
      from day 6 and reached that of M18 at day 12 (p = 0.04). Leukocyte-endothelium
      interaction showed sticker counts elevated by a factor of 4-5 in M18 as compared
      to M16. Mineralization of osteochondral grafts did not differ between M16 and
      M18, which significantly increased in both groups throughout the observation
      period. INTERPRETATION: We propose the faster kinetics in the angiogenic response
      to M18 and the elevated counts of sticking leukocytes to rest on the potential of
      establishing end-to-end anastomoses (inosculation) of the vascularized graft with
      recipient vessels.

PMID- 15260433
TI  - Internet based counseling to remote orthopedic patients.

PMID- 15260434
TI  - No difference between daily and weekly pin site care.

PMID- 15260435
TI  - The C-terminal cytoplasmic tail of claudins 1 and 5 but not its PDZ-binding motif
      is required for apical localization at epithelial and endothelial tight
      junctions.
AB  - Claudins are a family of tetraspan transmembrane proteins that represent the
      major constituents of epithelial and endothelial tight junctions (TJs). They form
      TJ strands representing the major barrier regulating paracellular transport of
      solutes and water. Intracellularly, claudins are connected via a C-terminal PDZ
      binding motif with several TJ-associated proteins containing PDZ domains.
      Although these interactions can provide a link to the actin cytoskeleton, they
      appear to be dispensable for the TJ localization of claudins. To identify TJ
      targeting elements in the C-terminal cytoplasmic domains of the claudins 1 and 5,
      we generated a series of C-terminal deletion mutants and analyzed their
      distribution in polarized epithelial (MDCK) and endothelial (HMEC-1) cells. TJ
      localization was revealed by establishing an in vivo cross-linking approach that
      stabilized claudin-TJ interactions. We show that residues located C-terminal to
      the last transmembrane domain are required for the proper targeting to apical
      TJ.s. While claudin derivatives lacking only the very C-terminal PDZ-binding
      motif continue to localize to TJs, mutants lacking the entire C-terminal
      juxtamembrane sequence do not associate with TJs and accumulate in intracellular
      structures. This indicates that crucial determinants for stable TJ incorporation
      of claudins reside in a cytoplasmic C-terminal sequence which up to now has not
      been implicated in specific protein-protein interactions.

PMID- 15260436
TI  - A novel aspartic proteinase is targeted to the secretory pathway and to the
      vacuole in the moss Physcomitrella patens.
AB  - In seed plants aspartic proteases (APs) are known to reside in storage vacuoles.
      Targeting to this compartment is provoked by a secretory signal peptide and the
      plant-specific insert (PSI). In order to study secretory and vacuolar targeting
      in a seedless plant, the moss Physcomitrella patens, we isolated a cDNA encoding
      PpAP1, a novel aspartic proteinase. Sequence alignment with other members of the
      family of plant APs (EC 3.4.23) revealed a high overall identity and the Pfam
      motifs for aspartic proteinase and PSI were clearly recognised. In phylogenetic
      analysis PpAP1 was placed at a very basal position outside of the bigger
      clusters. Protoplasts transiently expressing the PpAP1 signal peptide fused to
      GFP showed fluorescence in a well-developed ER-Golgi network. A C-terminal fusion
      of GFP to the entire PpAP1 protein showed vacuolar fluorescence in transiently
      transfected protoplasts. Therefore, the vacuole is apparently the in-vivo target
      for PpAP1. In this study the three-dimensional peculiarity of the endomembrane
      continuum of ER and Golgi was visualised in a seedless plant for the first time.
      Above all the functionality of the secretory and the vacuolar targeting signals
      make them become useful tools for biotechnological approaches.

PMID- 15260437
TI  - Mycobacterium tuberculosis and Mycobacterium avium modify the composition of the
      phagosomal membrane in infected macrophages by selective depletion of cell
      surface-derived glycoconjugates.
AB  - The growth of pathogenic mycobacteria in phagosomes of the host cell correlates
      with their ability to prevent phagosome maturation. The underlying molecular
      mechanism remains elusive. In a previous study, we have shown that Mycobacterium
      avium depletes the phagosome membrane of cell surface-derived glycoconjugates (de
      Chastellier and Thilo, Eur. J. Cell Biol. 81, 17-25, 2002). We now extended these
      quantitative observations to the major human pathogen, Mycobacterium tuberculosis
      (H37Rv). At increasing times after infection of mouse bone marrow-derived
      macrophages, cell-surface glycoconjugates were labelled enzymatically with
      [3H]galactose. Subsequent endocytic membrane traffic resulted in a redistribution
      of this label from the cell surface to endocytic membranes, including phagosomes.
      The steady-state distribution was measured by quantitative autoradiography at the
      electron microscope level. Relative to early endosomes, with which phagosomes
      continued to fuse and rapidly exchange membrane constituents, the phagosome
      membrane was depleted about 3-fold, starting during infection and in the course
      of 9 days thereafter. These results were in quantitative agreement with our
      previous observations for Mycobacterium avium. For the latter case, we now showed
      by cell fractionation that the depletion was selective, mainly involving
      glycoproteins in the 110-210 kDa range. Together, these results indicated that
      pathogenic mycobacteria induced and maintained a bulk change in phagosome
      membrane composition that could be of special relevance for survival of
      pathogenic mycobacteria within phagosomes.

PMID- 15260438
TI  - Use of nanotopography to study mechanotransduction in fibroblasts--methods and
      perspectives.
AB  - The environment around a cell during in vitro culture is unlikely to mimic those
      in vivo. Preliminary experiments with nanotopography have shown that nanoscale
      features can strongly influence cell morphology, adhesion, proliferation and gene
      regulation, but the mechanisms mediating this cell response remain unclear. In
      this perspective article, we attempt to illustrate that a possible mechanism is
      direct transmittal of forces encountered by cells during spreading to the nucleus
      via the cytoskeleton. We further try to illustrate that this 'self-induced'
      mechanotransduction may alter gene expression by changing interphase chromosome
      positioning. Whilst the observations described here to show how we think
      nanotopography can be developed as a tool to look at mechanotransduction are
      preliminary, we feel they indicate that topography may give cell biologists a non
      invasive tool with which to investigate in vitro cellular mechanisms.

PMID- 15260439
TI  - Extinction by infection? Effects of disease on biodiversity.

PMID- 15260440
TI  - Suspected adverse reactions, 2003.

PMID- 15260441
TI  - Investigation of trace elements in soil as risk factors in the epidemiology of
      scrapie.
AB  - Scrapie is a fatal transmissible spongiform encephalopathy (TSE) of sheep and
      goats which is thought to be caused by a conformational change of the normal
      prion protein to its pathological isoform. It has been speculated that this
      change may be mediated by an interaction between the prion protein and various
      trace elements, in particular manganese and copper, and that the levels of trace
      elements in soils may therefore be risk factors for TSEs. This hypothesis was
      tested by comparing the level of trace elements in the soils on farms with and
      without scrapie and on those with a higher and lower incidence of the disease.
      The levels of trace elements were obtained from the UK's National Soil Inventory
      and deficiencies reported by farmers. The results provide no evidence that trace
      elements are risk factors for scrapie on farms, and the variations in the levels
      of trace elements in soils at regional scales do not account for the regional
      differences in the prevalence of scrapie.

PMID- 15260442
TI  - Effects of different glucocorticoid treatments on serum acute phase proteins in
      dogs.
AB  - The serum concentrations of haptoglobin, caeruloplasmin, C-reactive protein and
      serum amyloid A were measured in three groups of seven healthy dogs. Group 1
      received a single dose of 1.1 mg/kg methylprednisolone acetate, administered
      subcutaneously; group 2 received 1 mg/kg per day of prednisone administered
      orally for three weeks; and group 3 received 2.2 mg/kg per day of prednisone
      administered orally for seven days. Before the administration of the
      glucocorticoids the serum concentrations of all the acute phase proteins were
      within the authors' laboratory reference ranges. After the administration of the
      drugs there were significant increases in the concentration of haptoglobin in all
      three groups, the increases being larger in groups 2 and 3. In contrast, the
      concentrations of C-reactive protein, caeruloplasmin and serum amyloid A were not
      affected.

PMID- 15260443
TI  - Scoring system for evaluating the stress to cattle of commercial loading and
      unloading.
AB  - The loading and unloading of cattle for road transport is stressful but the
      stress is difficult to evaluate in terms of the welfare of the cattle. Over one
      year, 40 normal commercial journeys in northern Spain were analysed in terms of
      time limits and behavioural events in order to design an objective method for
      assessing the stresses imposed on the animals, and a scoring method was developed
      for assessing the welfare of the animals during loading and unloading. Several
      definitions of time intervals were assessed to calculate a time score per animal,
      and easily observable behavioural events were scored and combined with the time
      score to obtain a total loading/unloading score. More than half of the loadings
      and unloadings involved turns, slips and vocalisations. Mounts and bouts of
      fighting were infrequent and balks and falls were significantly more frequent
      during loading than unloading. The plasma concentrations of cortisol, glucose and
      lactate, the activity of creatine kinase and the pH of the meat 24 hours after
      the animals were slaughtered were also measured. The results indicated that
      loading was more stressful than unloading and that higher scores implied
      significantly higher levels of stress.

PMID- 15260444
TI  - Simple PCR-based test for the detection of canine leucocyte adhesion deficiency.

PMID- 15260445
TI  - Reproductive disturbances and sex chromosome abnormalities in two female river
      buffaloes.

PMID- 15260446
TI  - Temporal shedding and persistence of porcine reproductive and respiratory
      syndrome virus in boars.

PMID- 15260447
TI  - Prevalence of enteropathogenic bacteria and Cryptosporidium species in moose
      (Alces alces) in Norway.

PMID- 15260448
TI  - Funding animal health and welfare.

PMID- 15260449
TI  - Slaughter without prestunning.

PMID- 15260450
TI  - Slaughter without prestunning.

PMID- 15260451
TI  - National Scrapie Plan: Compulsory Scrapie Flocks Scheme.

PMID- 15260452
TI  - Potentially novel segmental polioencephalomyelitis in weaner pigs.

PMID- 15260453
TI  - Polioencephalomyelitis of unknown aetiology in a heifer.

PMID- 15260454
TI  - Parrots and TVs.

PMID- 15260455
TI  - 24-hour cover.

PMID- 15260456
TI  - National Pet Week.

PMID- 15260457
TI  - Does bronchial hyperresponsiveness in asthma matter?
AB  - Bronchial hyperresponsiveness is a fundamental component of the asthmatic
      inflammatory process causing airway narrowing on exposure to a bronchoconstrictor
      stimulus. This in turn causes patients to experience symptoms of breathlessness,
      chest tightness, cough and wheeze. Bronchial challenge tests can be performed in
      the laboratory to establish the degree of bronchial hyperresponsiveness to both
      direct and indirect stimuli. The extent to which asthma pharmacotherapy
      attenuates bronchial hyperresponsiveness is therefore an important measure of
      efficacy. This review article discusses the effects of inhaled and oral asthma
      treatment upon bronchial hyperresponsiveness and highlights how, in conjunction
      with conventional measures of asthma control, it can be used as an aid to
      optimally manage patients.

PMID- 15260458
TI  - Residential exposure to volatile organic compounds and asthma.
AB  - We critically analysed the literature concerning exposure to volatile organic
      compounds and asthma. Observational studies have consistently found a relation
      between volatile organic compounds and indicators of asthma, such as symptoms,
      peak flows, and objectively measured bronchial reactivity. In contrast,
      interventional studies have generally failed to find a relation between exposure
      to residential levels of formaldehyde and other volatile organic compounds and
      asthma. One hypothesis to explain the discrepancy in findings between
      interventional and observational studies is that the effect size is small
      requiring relatively large numbers of study subjects, common in observational
      studies but often not feasible in interventional studies. Another hypothesis is
      that longer duration of exposure is important, a common circumstance in
      observational studies where the home environment is the exposure setting. In
      contrast, duration of exposure in interventional studies is usually of minutes-to
      hours in a chamber. Finally, the observed association in observational studies
      could be confounded by a factor which is a determinant of asthma and is also
      associated with exposure to volatile organic compounds.

PMID- 15260459
TI  - Determinants of the severity of exercise-induced bronchoconstriction in patients
      with asthma.
AB  - AIM: In examining the mechanisms of exercise-induced bronchoconstriction (EIB),
      it is important to determine which factors most strongly affect the severity of
      EIB. We determined such factors in patients with asthma by stepwise multiple
      regression analysis. METHODS: Twenty-three patients with asthma underwent
      pulmonary function tests, methacholine provocation test, and sputum induction.
      Eosinophilic inflammatory indices and airway vascular permeability index (ratio
      of albumin concentrations in induced sputum and serum) were examined in sputum
      samples, and then an exercise test was performed by all asthmatics. RESULTS:
      There was a significant correlation between the severity of EIB and degree of
      eosinophilic inflammation in induced sputum. Moreover, there was a significant
      correlation between the severity of EIB and airway vascular permeability index.
      Although we could not find a significant correlation between the severity of EIB
      and 1-sec forced expired volume, 20% provocation concentration of (PC20)
      methacholine tended to be correlated with the severity of EIB. By stepwise
      multiple-regression analysis, we also found that airway vascular permeability
      index, eosinophil cationic protein levels in sputum, and PC20 methacholine are
      independent predictors of the severity of EIB. CONCLUSION: We found that airway
      vascular hyperpermeability, eosinophilic inflammation, and bronchial
      hyperreactivity are independent factors predicting the severity of EIB.

PMID- 15260460
TI  - Influenza vaccination in patients with asthma: effect on the frequency of upper
      respiratory tract infections and exacerbations.
AB  - Influenza epidemics of variable extent and severity occur every winter and are
      frequently associated with exacerbations of asthma. Accordingly, annual
      vaccination against influenza is recommended for patients with asthma. However,
      there are very limited data concerning its protective effect in this group of
      patients. The aim of this study was to assess the effect of influenza vaccination
      on the frequency of upper respiratory tract infections and also asthma-related
      outcomes such as exacerbation rates, hospital admissions, and rescue courses of
      oral corticosteroids in patients with stable asthma. Between September 15 and
      November 7, 2001, a total of 128 patients with asthma were randomly assigned to
      receive (n = 86) and not to receive vaccine (n = 42). The primary outcome
      measures were frequency of upper respiratory tract infections and exacerbations
      of asthma during the winter following vaccination. Study subjects were asked to
      record the presence and duration of symptoms suggestive of an upper respiratory
      tract infection and call their physician in the presence of conditions suggestive
      of an exacerbation until March 2002. Among the vaccinated group, 48% of the
      patients reported that they had no upper respiratory tract infection during the
      winter following injection, whereas 57% of nonvaccinated participants were upper
      respiratory symptom free during the same period (p > 0.05). The frequency of
      upper respiratory tract infection was also not different between the two groups
      in all severity forms of asthma (p > 0.05). There was no significant difference
      in the frequency of exacerbations of asthma between the two groups during the
      study period (p > 0.05). None of the vaccinated group was hospitalized due to an
      asthma attack; however, two patients (4.8%) in the nonvaccinated group had to be
      hospitalized following an exacerbation (p > 0.05). In summary, our findings do
      not support the protective effect of influenza vaccination for patients with
      asthma. However, no firm conclusions on this effect of the vaccine can be made
      without the data on the rate of influenza epidemic in that season and without the
      knowledge of the cause of upper respiratory tract infections in those patients.
      Therefore, we believe randomized, double-blind, placebo-controlled studies,
      including larger subgroups of severe asthmatics, are needed to evaluate the
      protective effect of influenza vaccination in asthma.

PMID- 15260461
TI  - Immune modulator pidotimod decreases the in vitro expression of CD30 in
      peripheral blood mononuclear cells of atopic asthmatic and normal children.
AB  - Recurrent viral infections are frequently observed in children with atopic
      asthma. In this study we investigated the ability of the synthetic
      immunomodulator pidotimod to affect in vitro the phenotype and/or cytokine
      profile of blood cells in relation to atopic asthma. Peripheral blood mononuclear
      cells were isolated from 13 atopic asthmatic and 9 normal children and stimulated
      in culture with mitogen either in the presence or not of the drug. Expression of
      surface markers was evaluated by flow cytometry, and production of interleukin-4
      and interferon-gamma was measured in supernatants. Pidotimod was able to down
      regulate the expression of CD30 on cells from both atopic and normal subjects.
      Because CD30 has been associated with Th-2 cells, this observation supports the
      possibility of pidotimod being able to affect the Th-1/Th-2 balance in atopic
      asthma.

PMID- 15260462
TI  - Association between traffic volume and health care use for asthma among residents
      at a U.S.-Canadian border crossing point.
AB  - Little information is available about health impacts of the North American Free
      Trade Agreement (NAFTA) traffic-related pollution on residents near the major
      traffic corridors along the U.S.-Canadian border. Here we report on a 10 year
      (1991-2000) retrospective study of commercial traffic volumes across the Peace
      Bridge and health care use for asthma in a residential community, which serves as
      a conduit for traffic crossing between Fort Erie, Ontario, Canada, and Buffalo,
      New York. We hypothesized that commercial traffic pollution was impacting on
      residents in close proximity to the trade corridor. Commercial traffic volumes,
      hospital discharges for asthma, and outpatient visits to area hospitals and
      clinics were analyzed before and after implementation of NAFTA. Results showed a
      positive association between increased commercial traffic volume and increased
      health care use for asthma. Zip codes 14201 and 14213, which surround the Peace
      Bridge Plaza Complex (PBC), had the highest prevalence rates and health care use
      rates for asthma. Statistical analysis showed the findings to be significant (p <
      0.05) in that residential proximity to the PBC was associated with greater
      hospital discharge rates for asthma. The findings were strongest (p < 0.000) in
      the zip codes where the PBC was located (14213) and the major highway I-190
      passed through (14201). A yearly excess of 230.2 adult asthma hospital discharges
      was associated with an increase in traffic volume during the period from 1991 to
      1996 in the study area. This is in contrast to an overall decrease in the
      national rate of hospitalizations for asthma by 7.5% in the same period. The
      results suggest that NAFTA-related commercial traffic has a negative health
      impact on asthmatics living in close proximity to the trade corridor. Health and
      social costs due to traffic pollution need to be included in cost estimates of
      transport decisions related to the NAFTA corridors. Similar health effects due to
      NAFTA traffic need to be studied at other U.S.-Canada border crossing points.

PMID- 15260463
TI  - The reuse of subjects in clinical studies: is a bias introduced? Is there a
      threat to study validity?
AB  - The reuse of subjects in clinical studies to answer specific research questions
      is a common practice. This reuse can take many forms and is at least partly
      related to study efficiency. It is much easier to reuse known subjects who know
      the system(s) or are easy to find than to recruit new ones. A hypothetical
      question is: Are there instances when such practices may not be scientifically
      valid? This question will be addressed from the perspective of the case-control
      and experimental study design.

PMID- 15260464
TI  - Incidence and prevalence of asthma and allergic rhinitis: a cohort study of
      Finnish adolescents.
AB  - Only limited data are available about the incidence of asthma and allergic
      rhinitis based on prospective longitudinal studies throughout childhood into
      adult life. The main purpose of the study was to estimate the incidence rate of
      asthma and allergic rhinitis from birth to early adulthood. We also estimated the
      prevalences of these diseases at 16, 22, and 32 years of age. The data were drawn
      from a follow-up survey of a Finnish urban age cohort (1967 birth cohort, N =
      2269) from age 16 to age 32 years. All data were based on self-report. The
      prevalence of asthma from age 16 to age 32 years changed from 3.0% to 5.0% (males
      from 3.3% to 4.9%; females from 2.7% to 5.1%); and that of allergic rhinitis from
      17.5% to 26.0% (males from 18.7% to 27.8%; females 16.2% to 24.5%), respectively.
      The overall incidence rate of asthma was approximately 2.1 new cases per 1000
      person-years (95% CI = 1.6-2.8). There was a tendency for boys to have a higher
      incidence rate of asthma than girls in childhood before 16 years of age: gender
      difference was reversed from period 17 to 22 years of age. In early adulthood (23
      32 years), incidence rates were equal in both sexes. The incidence rate for
      allergic rhinitis in males was 13.4 per 1000 person-years (95% CI- 11.8-14.8),
      slightly greater than in females, 11.4 (95% CI = 10.1-12.8). Among both genders,
      the highest incidence rate of allergic rhinitis was between 17 and 22 years. Our
      study adds to the limited knowledge on the incidence rates of asthma and allergic
      rhinitis.

PMID- 15260465
TI  - Ratio of omega-6 to omega-3 fatty acids and childhood asthma.
AB  - Asthma is a leading cause of morbidity for children and is a major public health
      problem in Australia. Ecological and temporal data suggest that dietary factors
      may have a role in recent increases in the prevalence of asthma. AIM: The aim of
      conducting this study was to investigate whether childhood asthma was associated
      with the ratio of omega 6 (n-6) to omega 3 (n-3) fatty acids in the diet (n-6:n
      3). METHOD: The Western Australian Pregnancy Cohort Study is a prospective birth
      cohort of 2602 children. Using a nested case-control cross-sectional study design
      within this cohort, a group of children were identified as cases with current
      asthma at 6 or at 8 years of age or as controls with no asthma at 6 or at 8
      years. Dietary details including n-6 and n-3 fatty acid intake data were
      collected by parent response to a questionnaire when the children were 8 years
      old. Logistical regression was used to compare quartiles of n-6:n-3 intake in
      cases and controls. Adjustment was made for covariates: gender, gestational age,
      breastfeeding, older siblings, maternal smoking during pregnancy, maternal age,
      maternal asthma, child's current age in months, body mass index, total energy
      intake, and antioxidant intake (vitamins A, C, E, and zinc). RESULTS: A response
      rate of 83% was achieved by providing complete data from 335 children [49% cases
      with current asthma (n = 166), 51% controls (n = 169)]. Following adjustment for
      covariates the association between the ratio of n-6:n-3 fatty acids and risk for
      current asthma was statistically significant (p = 0.022). CONCLUSION: We found
      evidence for a modulatory effect of the dietary n-6:n-3 fatty acid ratio on the
      presence of asthma in children. Our results provide evidence that promotion of a
      diet with increased n-3 fatty acids and reduced n-6 fatty acids to protect
      children against symptoms of asthma is warranted.

PMID- 15260466
TI  - Determinants of quality of life among people with asthma: findings from the
      Behavioral Risk Factor Surveillance System.
AB  - Asthma is a major contributor to impaired quality of life in the U.S. population.
      Little is known about population-based determinants of quality of life among
      people with asthma, however. Using data from the 2000 Behavioral Risk Factor
      Surveillance System, we examined the associations between selected
      sociodemographic, behavioral, and other determinants and quality of life among
      12,111 participants with current asthma. In multiple logistical regression
      models, three variables--employment status, smoking status, and physical activity
      -were significantly associated with all measures of impaired quality of life
      (poor or fair health, > or = 14 physically unhealthy days, > 14 mentally
      unhealthy days, > or = 14 activity limitation days, or > or = 14 physically or
      mentally unhealthy days). Education was significantly and inversely related to
      impaired quality of life for all measures except activity limitation days. Men
      were less likely than women to report having > or = 14 physically unhealthy days,
      > or = 14 mentally unhealthy days, or > or = 14 physically or mentally unhealthy
      days. Compared with whites, Hispanics were more likely to report being in poor or
      fair health, and African Americans were less likely to report having > or = 14
      physically unhealthy days or > or = 14 physically or mentally unhealthy days. In
      addition, participants with lower incomes were more likely to report impaired
      quality of life for three measures (general health status, > or = 14 physically
      unhealthy days, and activity limitation days). The heaviest participants were
      more likely to be in poor or fair health or to report having more > or = 14
      physically unhealthy days, or > or = 14 physically or mentally unhealthy days.
      Insurance coverage and the time since their last routine checkup were not
      significantly associated with any of the quality-of-life measures. These results
      show that three potentially modifiable factors (smoking status, physical
      activity, body mass index) are associated with quality of life among persons with
      asthma. Furthermore, among people with asthma, the elderly, women, poorly
      educated, and low-income participants are especially likely to experience
      impaired quality of life.

PMID- 15260467
TI  - Myocardial injury during standard treatment of an adult with status asthmaticus.
AB  - Asthma affects 5%-10% of adults in the United States. Older adults (> 65 years)
      with asthma have higher rates of fatal asthma than younger adults. The occurrence
      of a respiratory emergency, such as status asthmaticus, would seem likely to
      create a situation of cardiopulmonary dysfunction conducive to myocardial
      ischemia. However, multiple studies of fatal or near-fatal asthma have failed to
      incriminate myocardial infarction as a contributing factor. We report a patient
      without underlying coronary artery disease who sustained myocardial injury
      consistent with myocardial ischemia and infarction during status asthmaticus
      while receiving recommended treatment without intravenous sympathomimetics or
      theophylline.

PMID- 15260468
TI  - A national survey of asthma knowledge and practices among specialists and primary
      care physicians.
AB  - Asthma is a chronic disorder that causes significant morbidity and mortality and
      requires ongoing chronic care. Approximately two-thirds of people with asthma are
      receiving care from a primary care clinician, such as an internist, family
      practitioner, nurse practitioner, or pediatrician. The other one-third of
      patients are obtaining treatment and ongoing care from specialists, including
      allergists or pulmonologists. The outcomes of asthma care are a subject of
      intense investigation. Many studies focus on pharmacotherapy, allergen control,
      and asthma education as interventions to reduce the morbidity and costs
      associated with asthma. Fewer studies have explored the differences in outcomes
      between asthmatic patients cared for by specialists compared with generalists.
      Even fewer have explored the practice differences between generalists and
      specialists that may relate to outcomes of care. With the advent of national
      asthma guidelines and the high prevalence of asthma seen in primary care
      settings, it is important to investigate the knowledge, attitudes, and practices
      of primary care physicians with regard to asthma.

PMID- 15260469
TI  - Effect of inspiratory flow on methacholine challenge in children.
AB  - Regulation of inspiratory flow alters the outcomes of the methacholine (MHC)
      challenge in adults and cough receptor sensitivity in children. The effect of
      inspiratory flow on the reproducibility of the MHC challenge in children is
      unknown. The aim of this study was to evaluate the effect of inspiratory flow
      alteration on the repeatabilty of the MHC challenge in children with and without
      asthma. Twenty-five children undertook the MHC challenge on three different days
      by using a dosimeter connected to a setup that allowed regulation of inspiratory
      flow and pattern. Children were randomized to commence the challenges at 20 or 60
      L/min, and the last challenge was performed at 20 L/min. The within-subject
      standard deviation, 95% range for change, and doubling dose for the differing
      inspiratory flow (20 vs. 60 L/min) was more than twice that of when inspiratory
      flow was maintained at 20 L/min for both occasions. The range of the "limits of
      agreement" of the Bland and Altman plot was smaller when inspiratory flow was
      constant. For short-term comparative individual studies in children, inspiratory
      flow should be regulated. Laboratories and research measuring change in airway
      hyperrepsonsiveness to MHC should determine and report reproducibility indices of
      the challenge so airway hyperresponsiveness changes can be interpreted
      meaningfully.

PMID- 15260470
TI  - Possible maximal change in the SF-36 of outpatients with chronic obstructive
      pulmonary disease and asthma.
AB  - The purpose of the present study was to investigate the responsiveness of the
      Short Form-36 (SF-36) in patients with chronic obstructive pulmonary disease
      (COPD) and asthma. We studied patients with COPD and asthma who attended our
      outpatient clinic. In the first cross-sectional study, we compared the
      differences in the SF-36 scores between pretreatment patients (152 with COPD and
      174 with asthma) who visited the clinic for the first time and in-treatment
      patients (123 with COPD and 151 with asthma) who had received treatment for > 6
      months. The differences in each scale of the SF-36 ranged from 6.9 to 14.4 in
      COPD patients and from 7.0 to 28.3 in asthma patients. In the second longitudinal
      study, patients who visited for the first time were enrolled, and the initial,
      and, 3-, 6-, and 12-month evaluations of the SF-36 were studied. A total of 136
      COPD patients and 136 asthma patients were enrolled consecutively, and 100
      patients with COPD and 66 patients with asthma completed the year-long
      examinations. In COPD patients, except for bodily pain, the scores in all scales
      of the SF-36 improved significantly during the first 3 or 6 months. In patients
      with asthma, all scale scores of the SF-36 improved significantly during the
      first 3 months. Maximal changes in the SF-36 scores were observed at 6 or 12
      months. Longitudinal maximal changes in each scale approached or exceeded the
      possible maximal changes, which were derived from the differences in the scores
      between pretreatment patients and in-treatment patients in the first cross
      sectional study. Improvements in the SF-36 scores showed moderate to strong
      negative correlations with their baseline scores in patients with COPD and
      asthma. In conclusion, the SF-36 shows sufficient responsiveness in the
      assessment of the health status of patients with COPD and asthma, but these
      responses are strongly influenced by their baseline values.

PMID- 15260471
TI  - Lack of awareness of need to clean CFC-free metered-dose inhalers.
AB  - BACKGROUND: Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were
      introduced into Australia in 1999. Device care instructions were modified (e.g.,
      CFC-free salbutamol inhalers to be washed weekly), but this information was not
      communicated directly to health care professionals. OBJECTIVE: This pilot study
      aimed to assess the level of awareness of device care protocols for CFC-free MDIs
      by patients and their pharmacists. SETTING AND DESIGN: Purchasers of CFC-free
      MDIs were recruited from four community pharmacies. They were interviewed
      regarding information sources, knowledge of propellant change, and awareness of
      and adherence to device care protocols. The dispensing pharmacists were
      interviewed for knowledge of CFC-free device care. The primary outcome variable
      was awareness of the relevant device care protocol. RESULTS: Thirty-nine patients
      were interviewed. Most patients (77%) were aware of the change to CFC-free
      propellant. Only nine patients (23%) were aware of the need to wash the device
      holder, and four patients (10% of total) complied with the specified protocol.
      One of the ten dispensing pharmacists could describe correct device care
      protocols for the CFC-free MDIs. CONCLUSIONS: Although most patients are aware
      that MDIs are now CFC-free, there is a low level of awareness of the device care
      required for these inhalers, and a very low rate of compliance with recommended
      practice. Although the clinical impact of failing to wash the device holder is
      unclear, this added instruction may have substantial implications for patient
      satisfaction and medication delivery. Pharmaceutical manufacturers need to
      highlight to health care professionals any clinically important changes in device
      care instructions, so that appropriate information may be passed on to patients.

PMID- 15260472
TI  - Homology modeling of the human microsomal glucose 6-phosphate transporter
      explains the mutations that cause the glycogen storage disease type Ib.
AB  - Glycogen storage disease type Ib is caused by mutations in the glucose 6
      phosphate transporter (G6PT) in the endoplasmic reticulum membrane in liver and
      kidney. Twenty-eight missense and two deletion mutations that cause the disease
      were previously shown to reduce or abolish the transporter's activity. However,
      the mechanisms by which these mutations impair transport remain unknown. On the
      basis of the recently determined crystal structure of its Escherichia coli
      homologue, the glycerol 3-phosphate transporter, we built a three-dimensional
      structural model of human G6PT by homology modeling. G6PT is proposed to consist
      of 12 transmembrane alpha-helices that are divided into N- and C-terminal
      domains, with the substrate-translocation pore located between the two domains
      and the substrate-binding site formed by R28 and K240 at the domain interface.
      The disease-causing mutations were found to occur at four types of positions: (I)
      in the substrate-translocation pore, (II) at the N-/C-terminal domain interface,
      (III) in the interior of the N- and C-terminal domains, and (IV) on the protein
      surface. Whereas class I mutations affect substrate binding directly, class II
      mutations, mostly involving changes in side chain size, charge, or both, hinder
      the conformational change required for substrate translocation. On the other
      hand, class III and class IV mutations, often introducing a charged residue into
      a helix bundle or at the protein-lipid interface, probably destabilize the
      protein. These results also suggest that G6PT operates by a similar antiport
      mechanism as its E. coli homologue, namely, the substrate binds at the N- and C
      terminal domain interface and is then transported across the membrane via a
      rocker-switch type of movement of the two domains.

PMID- 15260473
TI  - Might the kinetic behavior of hormone-sensitive lipase reflect the absence of the
      lid domain?
AB  - Hormone-sensitive lipase (HSL) is thought to contribute importantly to the
      mobilization of fatty acids from the triacylglycerols (TAGs) stored in
      adipocytes, providing the main source of energy in mammals. To investigate the
      HSL substrate specificity more closely, we systematically assessed the lipolytic
      activity of recombinant human HSL on solutions and emulsions of various vinyl
      esters and TAG substrates, using the pH-stat assay technique. Recombinant human
      HSL activity on solutions of partly soluble vinyl esters or TAG was found to
      range from 35 to 90% of the maximum activity measured with the same substrates in
      the emulsified state. The possible existence of a lipid-water interface due to
      the formation of small aggregates of vinyl esters or TAG in solution may account
      for the HSL activity observed below the solubility limit of the substrate.
      Recombinant human HSL also hydrolyzes insoluble medium- and long-chain
      acylglycerols such as trioctanoylglycerol, dioleoylglycerol, and olive oil, and
      can therefore be classified as a true lipase. Preincubation of the recombinant
      HSL with a serine esterase inhibitor such as diethyl p-nitrophenyl phosphate in
      1:100 molar excess leads to complete HSL inhibition within 15 min. This result
      indicates that the catalytic serine of HSL is highly reactive and that it is
      readily accessible. Similar behavior was also observed with lipases with no lid
      domain covering their active site, or with a deletion in the lid domain. The 3-D
      structure of HSL, which still remains to be determined, may therefore lack the
      lid domain known to exist in various other lipases.

PMID- 15260474
TI  - Rat alpha- and beta-parvalbumins: comparison of their pentacarboxylate and site
      interconversion variants.
AB  - Introduction of a fifth carboxylate into the ligand array of the CD site (via the
      combined S55D and E59D mutations) or the EF site (G98D) of rat alpha-parvalbumin
      substantially increases divalent ion affinity. This behavior, in conflict with
      that seen in model peptide systems, agrees with existing data for rat beta
      parvalbumin [Henzl et al. (1996) Biochemistry 35, 5856-5869]. The complete
      analysis of the S55D/E59D double variant necessitated characterization of alpha
      E59D. Whereas the D59E mutation has minimal influence on beta CD site affinity,
      E59D has a major impact on the alpha CD site, lowering the apparent association
      constant by a factor of 14. The thermodynamic consequences of exchanging the rat
      alpha CD and EF site ligand arrays, which differ at the +z and -x coordination
      positions, were also examined. When the alpha CD array is imported into the EF
      site, it acquires a low-affinity phenotype, in agreement with previous findings
      for beta [Henzl et al. (1998) Biochemistry 37, 9101-9111]. However, when the EF
      ligand array is introduced into the alpha CD binding loop, it retains a high
      affinity signature. This result, contrary to that observed in beta, suggests that
      the influence of the parvalbumin CD site environment supersedes the intrinsic
      behavior of the ligand array, a conclusion further supported by the disparate
      impact of the beta D59E and alpha E59D mutations.

PMID- 15260475
TI  - Energetics and mechanism of Ca2+ displacement by lanthanides in a calcium binding
      protein.
AB  - The displacement of Ca(2+) by trivalent lanthanide ions (Tm(3+)) in a protozoan
      (Entamoeba histolytica) Ca(2+) binding protein has been studied by NMR and
      isothermal calorimetry (ITC). The study provides a basis for understanding the
      behavior of lanthanides when used as a substitute for Ca(2+), the pattern of
      sequential binding, the structural changes involved, the range and magnitude of
      paramagnetic interaction, and the associated energetics and mechanism. The
      progressive Ca(2+) displacement from site III first, followed by displacement
      from site II, I, and IV, as observed during the NMR titration experiments, is
      interpreted in the light of ITC data to provide a deeper insight into the
      intradomain and, for the first time, interdomain cooperativity and information
      about the statistical phenomenon involved in it. A theoretical model governing
      Ca(2+) displacement is provided. The small structural changes involved in Ca(2+)
      displacement by a diamagnetic lanthanide (La(3+)) has also been monitored.

PMID- 15260476
TI  - Backbone dynamics of the RNase H domain of HIV-1 reverse transcriptase.
AB  - Previous NMR relaxation studies of the isolated RNase H domain of HIV-1 reverse
      transcriptase at low pH have revealed that it is substantially more dynamic and
      less ordered than the relatively stable and catalytically active E. coli RNase
      HI. Using more recently developed techniques, we have investigated the dynamic
      behavior of the RNase H domain of HIV-1 reverse transcriptase at a more
      physiological pH (6.8), under a variety of solution conditions: no Mg(2+), 80 mM
      Mg(2+), and 80 mM Mg(2+) plus AMP ligand. In addition, we have repeated the
      previous measurements on a sample containing 100 mM sodium acetate, pH 5.4. Under
      all conditions studied, the order parameters from NMR relaxation analysis are
      uniformly high (>0.8) for most of the domain with the exception of the C-terminal
      region. Subtle differences can be found among the conditions studied, although
      the statistical significance of the differences is marginal. Residues 71-114 show
      a slight increase in order parameter with the addition of 5'-AMP. Conformational
      exchange, measured with CPMG relaxation dispersion experiments in the presence of
      Mg and AMP, were detected for some NH sites, predominantly located in the N
      terminal region of the protein near strands beta2 and beta3 and helix alpha(A)
      (residues 28-69). In contrast with earlier studies indicating pathologically
      extreme dynamic behavior that apparently correlated with inactivity of the
      isolated domain, the relaxation analysis under the conditions of the present
      study yielded parameters that are more similar to those of the active E. coli
      RNase HI. A comparison of the order parameters obtained from a model-free
      analysis of the relaxation data with the B-factors in the crystal structures of
      the RNase H domain, both for the isolated domain and for the full HIV-1 reverse
      transcriptase structure, suggests that the dynamic behavior is similar in all
      cases.

PMID- 15260477
TI  - pH-Dependent conformational changes and topology of a herpesvirus translocating
      peptide in a membrane-mimetic environment.
AB  - Pol peptide, an oligopeptide corresponding to the 27 C-terminal amino acids of
      DNA polymerase from herpes simplex virus type 1, has recently been suggested to
      translocate from endosomal compartments into the cytosol after being
      intracellularly delivered via a protein carrier. While an acidic environment was
      thought to be important for Pol peptide membrane translocation, the mechanism of
      translocation remains unclear. To investigate the influence of an acidic
      environment on the conformational properties of the peptide and on its propensity
      to interact with lipid bilayers, we characterized the structure of Pol peptide at
      different pH values by both circular dichroism (CD) and nuclear magnetic
      resonance (NMR) spectroscopy. The influence of detergent micelles, which mimic
      biological lipid membranes, on the peptide secondary structure was also studied.
      Our CD results indicate that the peptide is in a random conformation in aqueous
      solution at both acidic and basic pH, whereas in the presence of
      dodecylphosphocholine (DPC) micelles, it assumes a partial alpha-helical
      structure which is significantly pH-dependent. An NMR study confirmed that, in
      the presence of DPC micelles, a short C-terminal alpha-helix is present at pH
      6.5, whereas almost two-thirds of the peptide (residues 10-26) fold into an
      extended amphipathic alpha-helix at pH 4.0. The orientation of Pol peptide
      relative to the DPC micelle was investigated using paramagnetic probes at both pH
      4.0 and 6.5. These studies show that the peptide inserts deeply into the micelle
      at pH 4.0, whereas it is more exposed to the aqueous environment at pH 6.5. On
      the basis of these results, a model which might explain the mechanism of
      translocation of Pol peptide from acidic endosomes to the cytosol is discussed.

PMID- 15260478
TI  - N-Terminal domain linkage modulates the folding properties of protein S epidermal
      growth factor-like modules.
AB  - Protein S interacts with activated protein C to play a crucial role in blood
      anticoagulation, and protein S deficiency is associated with increased risk of
      thrombosis. Despite the large volume of functional data available for this
      protein, no atomic resolution structure data have yet been reported. This is due
      at least in part to difficulties encountered when trying to produce fragments
      dissected from the intact protein; however, a few successful strategies have been
      described. In this research we have expressed a number of constructs containing
      protein S epidermal growth factor-like (EGF) domains 1 and 2 in Escherichia coli
      and Pichia pastoris. None of the proteins produced was stably folded as assayed
      by solution nuclear magnetic resonance spectroscopy. We therefore constructed a
      series of non-native protein S EGF concatemers to investigate the role of
      pairwise domain linkage in domain folding. Our results demonstrate that N
      terminal domain linkage can either positively or negatively impact on the
      refolding of an adjacent domain. Furthermore, analysis of the NMR data for EGF3-4
      reveals the expected interdomain NOEs that are characteristic of an extended
      arrangement of calcium-binding EGF domains and a similar average [(1)H]-(15)N
      heteronuclear NOE value for each of the two domains. These results provide the
      first data in support of protein S EGF3-4 adopting the same extended domain
      orientation as observed for the functionally distinct proteins fibrillin-1 and
      the low-density lipoprotein receptor. The results also have important
      implications for future studies, particularly when a dissection approach is used,
      of tandem EGF domains from protein S and other proteins.

PMID- 15260479
TI  - Solution NMR structure and X-ray absorption analysis of the C-terminal zinc
      binding domain of the SecA ATPase.
AB  - The solution NMR structure of a 22-residue Zn(2+)-binding domain (ZBD) from
      Esherichia coli preprotein translocase subunit SecA is presented. In conjunction
      with X-ray absorption analysis, the NMR structure shows that three cysteines and
      a histidine in the sequence CXCXSGX(8)CH assume a tetrahedral arrangement around
      the Zn(2+) atom, with an average Zn(2+)-S bond distance of 2.30 A and a Zn(2+)-N
      bond distance of 2.03 A. The NMR structure shows that ND1 of His20 binds to the
      Zn(2+) atom. The ND1-Zn(2+) bond is somewhat strained: it makes an angle of
      approximately 17 degrees with the plane of the ring, and it also shows a
      significant "in-plane" distortion of 13 degrees. A comprehensive sequence
      alignment of the SecA-ZBD from many different organisms shows that, along with
      the four Zn(2+) ligands, there is a serine residue (Ser12) that is completely
      conserved. The NMR structure indicates that the side chain of this serine residue
      forms a strong hydrogen bond with the thiolate of the third cysteine residue
      (Cys19); therefore, the conserved serine appears to have a critical role in the
      structure. SecB, an export-specific chaperone, is the only known binding partner
      for the SecA-ZBD. A phylogenetic analysis using 86 microbial genomes shows that
      59 of the organisms carry SecA with a ZBD, but only 31 of these organisms also
      possess a gene for SecB, indicating that there may be uncharacterized binding
      partners for the SecA-ZBD.

PMID- 15260480
TI  - Structural studies of two mutants of amicyanin from Paracoccus denitrificans that
      stabilize the reduced state of the copper.
AB  - Mutation of Pro94 to phenylalanine or alanine significantly alters the redox
      properties of the type I copper center of amicyanin. Each mutation increases the
      redox midpoint potential (E(m)) value by at least 140 mV and shifts the pK(a) for
      the pH dependence of the E(m) value to a more acidic value. Atomic resolution
      (0.99-1.1 A) structures of both the P94F and P94A amicyanin have been determined
      in the oxidized and reduced states. In each amicyanin mutant, an electron
      withdrawing hydrogen bond to the copper-coordinating thiolate sulfur of Cys92 is
      introduced by movement of the amide nitrogens of Phe94 and Ala94 much closer to
      the thiolate sulfur than in wild-type amicyanin. This is the likely explanation
      for the much more positive E(m) values which result from each of these mutations.
      The observed decrease in the pK(a) value for the pH dependence of the E(m) value
      that is seen in the mutants seems to be correlated with steric hindrance to the
      rotation of the His95 copper ligand which results from the mutations. In wild
      type amicyanin the His95 side chain undergoes a redox and pH-dependent
      conformational change which accounts for the pH dependence of the E(m) value of
      amicyanin. The reduced P94A amicyanin exhibits two alternate conformations with
      the positions of the copper 1.4 A apart. In one of these conformations, a water
      molecule appears to have replaced Met98 as a copper ligand. The relevance of
      these structures to the electron transfer properties of P94F and P94A amicyanin
      are also discussed.

PMID- 15260481
TI  - Crystallographic and NMR investigation of cobalt-substituted amicyanin.
AB  - Cobalt(II) amicyanin was prepared by replacing the copper of the type I copper
      protein amicyanin from Paracoccus denitrificans with cobalt. The structure of the
      protein and the metal center have been characterized by X-ray crystallography and
      paramagnetic NMR spectroscopy. The crystal structure indicates that Met98, which
      provides an axial sulfur ligand in native amicyanin, is no longer bound to the
      metal in cobalt(II) amicyanin and that a water molecule is recruited from solvent
      to form the fourth metal ligand. This results in a tetrahedral coordination
      geometry for the cobalt ion. NMR studies in solution also indicate that the side
      chain of the methionine residue interacts less strongly with the metal in P.
      denitrificans amicyanin than in Paracoccus versutus amicyanin. The cobalt(II)
      amicyanin crystal structure is different from that of cobalt-substituted azurin
      in which the carbonyl of a glycine residue provides this equivalent ligand. In
      cobalt(II) amicyanin that residue is a proline, for which the oxygen is
      structurally inaccessible, so that the water occupies the position held by the
      glycine carbonyl in cobalt(II) azurin. Such a metal coordination involving water
      has not previously been reported for a native or metal-substituted type I copper
      protein.

PMID- 15260482
TI  - The N-terminal domain of the Drosophila histone mRNA binding protein, SLBP, is
      intrinsically disordered with nascent helical structure.
AB  - Stem-loop binding protein (SLBP) is a 31 kDa protein that is central to the
      regulation of histone mRNAs and is highly conserved in metazoans. In vertebrates,
      the N-terminal domain of SLBP has sequence determinants necessary for histone
      mRNA translation, SLBP degradation, cyclin binding, and histone mRNA import. We
      have used high-resolution NMR spectroscopy and circular dichroism to characterize
      the structural and dynamic features of this domain of SLBP from Drosophila
      (dSLBP). We report that the N-terminal domain of dSLBP is stably unfolded but has
      nascent helical structure at physiological pH and native-like solution
      conditions. The conformational and dynamic properties of the isolated domain are
      mimicked in a longer 175-residue region of the N-terminus, as well as in the full
      length protein. Complete resonance assignments, secondary structure propensity,
      and motional properties of a 91-residue N-terminal domain (G17-K108) of dSLBP are
      reported here. The deviation of (1)H(alpha), (13)C(alpha), and (13)C(beta)
      chemical shifts from random coil reveals that there are four regions between
      residues I28-A45, S50-L57, S66-G75, and F91-N96 that have helical propensity.
      These regions also have small but positive heteronuclear NOEs, interresidue d(NN)
      NOEs, and small but significant protection from solvent exchange. However the
      lack of medium- and long-range NOEs in 3D (15)N- and (13)C-edited spectra, fast
      amide proton exchange rates (all greater than 1 s(-1)), and long (15)N relaxation
      (T(1), T(2)) times suggest that the domain from dSLBP does not adopt a well
      defined tertiary fold. The backbone residual dipolar couplings (RDCs) for this
      domain are small and lie close to 0 Hz (+/-2 Hz) for most residues with no well
      defined periodicity. The implications of this unfolded state for the function of
      dSLBP in regulating histone metabolism are discussed.

PMID- 15260483
TI  - Electrostatic contribution of serine phosphorylation to the Drosophila SLBP-
      histone mRNA complex.
AB  - Unlike all other metazoan mRNAs, mRNAs encoding the replication-dependent
      histones are not polyadenylated but end in a unique 26 nucleotide stem-loop
      structure. The protein that binds the 3' end of histone mRNA, the stem-loop
      binding protein (SLBP), is essential for histone pre-mRNA processing, mRNA
      translation, and mRNA degradation. Using biochemical, biophysical, and nuclear
      magnetic resonance (NMR) experiments, we report the first structural insight into
      the mechanism of SLBP-RNA recognition. In the absence of RNA, phosphorylated and
      unphosphorylated forms of the RNA binding and processing domain (RPD) of
      Drosophila SLBP (dSLBP) possess helical secondary structure but no well-defined
      tertiary fold. Drosophila SLBP is phosphorylated at four out of five potential
      serine or threonine sites in the sequence DTAKDSNSDSDSD at the extreme C
      terminus, and phosphorylation at these sites is necessary for histone pre-mRNA
      processing. Here, we provide NMR evidence for serine phosphorylation of the C
      terminus using (31)P direct-detect experiments and show that both serine
      phosphorylation and RNA binding are necessary for proper folding of the RPD. The
      electrostatic effect of protein phosphorylation can be partially mimicked by a
      mutant form of SLBP wherein four C-terminal serines are replaced with glutamic
      acids. Hence, both RNA binding and protein phosphorylation are necessary for
      stabilization of the SLBP RPD.

PMID- 15260484
TI  - Transmembrane helix 11 of multidrug resistance protein 1 (MRP1/ABCC1):
      identification of polar amino acids important for substrate specificity and
      binding of ATP at nucleotide binding domain 1.
AB  - Human multidrug resistance protein 1 (MRP1) is an ATP binding cassette (ABC)
      transporter that confers resistance to many natural product chemotherapeutic
      agents and can transport structurally diverse conjugated organic anions. MRP1 has
      three polytopic transmembrane domains (TMDs) and a total of 17 TM helices.
      Photolabeling and mutagenesis studies of MRP1 indicate that TM11, the last helix
      in the second TMD, may form part of the protein's substrate binding pocket. We
      have demonstrated that certain polar residues within a number of TM helices,
      including Arg(593) in TM11, are determinants of MRP1 substrate specificity or
      overall activity. We have now extended these analyses to assess the functional
      consequences of mutating the remaining seven polar residues within and near TM11.
      Mutations Q580A, T581A, and S585A in the predicted outer leaflet region of the
      helix had no detectable effect on function, while mutation of three residues
      close to the membrane/cytoplasm interface altered substrate specificity. Two of
      these mutations affected only drug resistance. N597A increased and decreased
      resistance to vincristine and VP-16, respectively, while S605A decreased
      resistance to vincristine, VP-16 and doxorubicin. The third, S604A, selectively
      increased 17beta-estradiol 17-(beta-d-glucuronide) (E(2)17betaG) transport. In
      contrast, elimination of the polar character of the residue at position 590 (Asn
      in the wild-type protein) uniformly impaired the ability of MRP1 to transport
      potential physiological substrates and to confer resistance to three different
      classes of natural product drugs. Kinetic and photolabeling studies revealed that
      mutation N590A not only decreased the affinity of MRP1 for cysteinyl leukotriene
      4 (LTC(4)) but also substantially reduced the binding of ATP to nucleotide
      binding domain 1 (NBD1). Thus, polar interactions involving residues in TM11
      influence not only the substrate specificity of MRP1 but also an early step in
      the proposed catalytic cycle of the protein.

PMID- 15260485
TI  - High-throughput protein structural analysis using site-directed fluorescence
      labeling and the bimane derivative (2-pyridyl)dithiobimane.
AB  - We present a site-directed fluorescence labeling (SDFL) study of 25 different T4
      lysozyme protein samples labeled with the thiol-cleavable fluorophore, (2
      pyridyl)dithiobimane (PDT-Bimane). Our results demonstrate PDT-Bimane can be used
      in cysteine-scanning studies to detect protein secondary structure, and to map
      proximity between sites in proteins by monitoring tryptophan quenching of bimane
      fluorescence. In addition, the reducible nature of PDT-Bimane can be exploited to
      resolve problems often faced in SDFL studies: ensuring specific labeling of
      cysteine residues, determining the extent of free label contamination, and
      accurately determining labeling efficiency even at low concentrations. The
      ability to cleave PDT-Bimane off the protein enables rapid determination of these
      parameters, and positions it as an ideal fluorophore for automated, high
      throughput structural studies of protein folding, the detection of protein
      protein interactions, and the monitoring of real-time conformational changes.

PMID- 15260486
TI  - Altered hydrogen bonding of Arg82 during the proton pump cycle of
      bacteriorhodopsin: a low-temperature polarized FTIR spectroscopic study.
AB  - Light-driven proton transport in bacteriorhodopsin (BR) is achieved by dynamic
      rearrangement of the hydrogen-bonding network inside the membrane protein. Arg82
      is located between the Schiff base region and proton release group, and has a
      major influence on the pK(a) values of these groups. It is believed that Arg82
      changes its hydrogen-bonding acceptors during the pump cycle of BR, stages of
      which are correlated with proton movement along the transport pathway. In this
      study, we compare low-temperature polarized FTIR spectra of [eta(1,2)
      (15)N]arginine-labeled BR in the 2750-2000 cm(-1) region with those of unlabeled
      BR for the K, L, M, and N intermediates. In the K-minus-BR difference spectra,
      (15)N-shifted modes were found at 2292 (-)/2266 (+) cm(-1) and at 2579 (-)/2567
      (+) cm(-1). The former corresponds to strong hydrogen bonding, while the latter
      corresponds to very weak hydrogen bonding. Both N-D stretches probably originate
      from Arg82, the former oriented toward water 406 and the latter toward the
      extracellular side, and both hydrogen bonds are somewhat strengthened upon
      retinal photoisomerization. This perturbation of arginine hydrogen bonding is
      entirely relaxed in the L intermediate where no (15)N-isotope shifts are observed
      in the difference spectrum. In the M intermediate, the frequency is not
      significantly altered from that in BR. However, the polarized FTIR spectra
      strongly suggest that the dipolar orientation of the strongly hydrogen bonded N-D
      group of Arg82 is changed from perpendicular to parallel to the membrane plane.
      Such a change is presumably related to the motion of the Arg82 side chain from
      the Schiff base region to the extracellular proton release group. Additional
      bands corresponding to weak hydrogen bonding were observed in both the M-minus-BR
      and N-minus-BR spectra. Changes in hydrogen-bonding structures involving Arg82
      are discussed on the basis of these FTIR observations.

PMID- 15260487
TI  - Mutational analysis of ABCG2: role of the GXXXG motif.
AB  - ABCG2 (BCRP/MXR/ABCP) is a half-transporter associated with multidrug resistance
      that presumably homodimerizes for function. It has a conserved GXXXG motif in its
      first transmembrane segment, a motif that has been linked with dimerization in
      other proteins, e.g., glycophorin A. We substituted either or both glycines of
      this GXXXG motif with leucines to evaluate the impact on drug transport, ATP
      hydrolysis, cross-linking, and susceptibility to degradation. All mutants also
      carried the R482G gain-of-function mutation, and all migrated to the cell
      surface. The mutations resulted in lost transport for rhodamine 123 and impaired
      mitoxantrone, pheophorbide a, and BODIPY-prazosin transport, particularly in the
      double leucine mutant (G406L/G410L). Basal ATPase activity of the G406L/G410L
      mutant was comparable to the empty vector transfected cells with no substrate
      induction. Despite impaired function, the mutants retained susceptibility to
      cross-linking using either disuccinimidyl suberate (DSS) or the reducible
      dithiobis(succinimidyl propionate) (DSP) and demonstrated a high molecular weight
      complex under nonreducing conditions. Mutations to alanine at the same positions
      yielded fully functional transporters. Finally, we exposed cells to mitoxantrone
      to promote folding and processing of the mutant proteins, which in the leucine
      mutants resulted in increased amounts detected on immunoblot and by
      immunofluorescence. These studies support a hypothesis that the GXXXG motif
      promotes proper packing of the transmembrane segments in the functional ABCG2
      homodimer, although it does not solely arbitrate dimerization.

PMID- 15260488
TI  - Formation of Meta III during the decay of activated rhodopsin proceeds via Meta I
      and not via Meta II.
AB  - Thermal isomerization of the retinal Schiff base C=N double bond is known to
      trigger the decay of rhodopsin's Meta I/Meta II photoproduct equilibrium to the
      inactive Meta III state [Vogel, R., Siebert, F., Mathias, G., Tavan, P., Fan, G.,
      and Sheves, M. (2003) Biochemistry 42, 9863-9874]. Previous studies have
      indicated that the transition to Meta III does not occur under conditions that
      strongly favor the active state Meta II but requires a residual amount of Meta I
      in the initial photoproduct equilibrium. In this study we show that the
      triggering event, the thermal isomerization of the protonated Schiff base, is
      independent of the presence of Meta II and occurs even under conditions where the
      transition to Meta II is completely prevented. We have examined two examples in
      which the transitions from Lumi to Meta I or from Meta I to Meta II are blocked.
      This was achieved using dry films of rhodopsin and rhodopsin reconstituted into
      rather rigid lipid bilayers. In both cases, the resulting fully inactive room
      temperature photoproducts decay specifically by thermal isomerization of the
      protonated Schiff base C=N double bond to an all-trans 15-syn chromophore isomer,
      corresponding to that of Meta III. This thermal isomerization becomes less
      efficient as the conformation of the respective photoproduct approaches that of
      Meta II and is fully absent in a pure Meta II state. These results indicate that
      the decay of the Meta I/Meta II photoproduct equilibrium to Meta III proceeds via
      Meta I and not via Meta II.

PMID- 15260489
TI  - A look within LHCII: differential analysis of the Lhcb1-3 complexes building the
      major trimeric antenna complex of higher-plant photosynthesis.
AB  - The major antenna complex of higher-plant photosynthesis, LHCII, is composed by
      the products of three genes, namely, Lhcb1-2-3. In this paper, the biochemical
      and spectroscopic properties of each of the three gene products were
      investigated. The three complexes were obtained by overexpression of the
      apoproteins in bacteria and refolding in vitro with purified pigments, thus
      allowing detection of differences in the structure/function of the pigment
      binding gene products. The analyses showed that Lhcb1 and Lhcb2 complexes have
      similar pigment binding properties, although not identical, while Lhcb3 is
      clearly different with respect to both pigment binding and spectral properties
      and cannot produce homotrimers in vitro. Heterotrimers containing Lhcb3 together
      with Lhcb1 and/or -2 proteins were obtained upon assembly with Lhcb proteins
      purified from thylakoids. The major functional characteristics of Lhcb3 with
      respect to Lhcb1 and -2 consisted in (i) a red-shift of one specific chlorophyll
      a chromophore, strongly affecting the red-most region of the absorption spectrum
      and (ii) a different specificity for xanthophylls binding to sites L2 and N1.
      These properties make Lhcb3 a relative sink for excitation energy in isolated
      heterotrimers with Lhcb1 + Lhcb2, and potentially, a preferential site of
      regulation of the antenna function in excess light conditions.

PMID- 15260490
TI  - ATR-FTIR spectroscopy studies of iron-sulfur protein and cytochrome c1 in the
      Rhodobacter capsulatus cytochrome bc1 complex.
AB  - Redox transitions in the Rhodobacter capsulatus cytochrome bc(1) complex were
      investigated by perfusion-induced attenuated total reflection-Fourier transform
      infrared (ATR-FTIR) spectroscopy combined with synchronous visible spectroscopy,
      in both the wild type and a cytochrome c(1) point mutant, M183K, in which the
      midpoint potential of heme was lowered from the wild-type value of 320 mV to 60
      mV. Overall redox difference spectra of the wild type and M183K mutant were
      essentially identical, indicating that the mutation did not cause any major
      structural perturbation. Spectra were compared with data on the bovine bc(1)
      complex, and tentative assignments of several bands could be made by comparison
      with available data on model compounds and crystallographic structures. The
      bacterial spectra showed contributions from ubiquinone that were much larger than
      in the bovine enzyme, arising from additional bound and adventitious ubiquinone.
      The M183K mutant enabled selective reduction of the iron-sulfur protein which in
      turn allowed the IR redox difference spectra of ISP and cytochrome c(1) to be
      deconvoluted at high signal/noise ratios, and features of these spectra are
      interpreted in light of structural and mechanistic information.

PMID- 15260491
TI  - Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a
      close structural homologue to D-camphor, the substrate for P450cam.
AB  - Cytochrome P450cin catalyzes the monooxygenation of 1,8-cineole, which is
      structurally very similar to d-camphor, the substrate for the most thoroughly
      investigated cytochrome P450, cytochrome P450cam. Both 1,8-cineole and d-camphor
      are C(10) monoterpenes containing a single oxygen atom with very similar
      molecular volumes. The cytochrome P450cin-substrate complex crystal structure has
      been solved to 1.7 A resolution and compared with that of cytochrome P450cam.
      Despite the similarity in substrates, the active site of cytochrome P450cin is
      substantially different from that of cytochrome P450cam in that the B' helix,
      essential for substrate binding in many cytochrome P450s including cytochrome
      P450cam, is replaced by an ordered loop that results in substantial changes in
      active site topography. In addition, cytochrome P450cin does not have the
      conserved threonine, Thr252 in cytochrome P450cam, which is generally considered
      as an integral part of the proton shuttle machinery required for oxygen
      activation. Instead, the analogous residue in cytochrome P450cin is Asn242, which
      provides the only direct protein H-bonding interaction with the substrate.
      Cytochrome P450cin uses a flavodoxin-like redox partner to reduce the heme iron
      rather than the more traditional ferredoxin-like Fe(2)S(2) redox partner used by
      cytochrome P450cam and many other bacterial P450s. It thus might be expected that
      the redox partner docking site of cytochrome P450cin would resemble that of
      cytochrome P450BM3, which also uses a flavodoxin-like redox partner.
      Nevertheless, the putative docking site topography more closely resembles
      cytochrome P450cam than cytochrome P450BM3.

PMID- 15260492
TI  - GammaM23K, gammaM232K, and gammaL77K single substitutions in the TF1-ATPase lower
      ATPase activity by disrupting a cluster of hydrophobic side chains.
AB  - In crystal structures of the bovine F(1)-ATPase (MF(1)), the side chains of
      gammaMet(23), gammaMet(232), and gammaLeu(77) interact in a cluster. Substitution
      of the corresponding residues in the alpha(3)beta(3)gamma subcomplex of TF(1)
      with lysine lowers the ATPase activity to 2.3, 11, and 15%, respectively, of that
      displayed by wild-type. In contrast, TF(1) subcomplexes containing the
      gammaM(23)C, gammaM(232)C, and gammaL(77)C substitutions display 36, 36, and
      130%, respectively, of the wild-type ATPase activity. The ATPase activity of the
      gammaM(23)C/gammaM(232)C double mutant subcomplex is 36% that of the wild-type
      subcomplex before and after cross-linking the introduced cysteines, whereas the
      ATPase activity of the gammaM(23)C/L(77)C double mutant increased from 50 to 85%
      that of wild-type after cross-linking the introduced cysteines. Only beta-beta
      cross-links formed when the alpha(3)(betaE(395)C)(3)gammaM(23)C double mutant was
      inactivated with CuCl(2). The overall results suggest that the attenuated ATPase
      of the mutant subcomplexes containing the gammaM(23)K, gammaL(77)K, and
      gammaM(232)K substitutions is caused by disruption of the cluster of hydrophobic
      amino acid side chains and that the midregion of the coiled-coil comprised of the
      amino- and carboxyl-terminal alpha helices of the gamma subunit does not undergo
      unwinding or major displacement from the side chain of gammaLeu(77) during ATP
      driven rotation of the gamma subunit.

PMID- 15260493
TI  - Cleavage-site mutagenesis alters post-translation processing of Pro-CCK in AtT-20
      cells.
AB  - Cholecystokinin (CCK) is expressed in the central and peripheral nervous systems
      and functions as a neurotransmitter and neuroendocrine hormone. The in vivo forms
      of CCK include CCK-83, -58, -39, -33, -22, -12, and -8. Tissues in the periphery
      produce the larger forms of CCK, such as CCK-58, whereas the brain primarily
      produces CCK-8. The different biologically active forms of CCK observed in vivo
      may result from cell-specific differences in endoproteolytic cleavage during post
      translational processing. Evidence suggests that cleavages of pro-CCK occur in a
      specific sequential order. To further delineate the progression of cleavages
      during pro-CCK maturation, mutagenesis was used to disrupt putative mono- and
      dibasic cleavage sites. AtT-20 cells transfected with wild-type rat prepro-CCK
      secret CCK-22 and -8. Mutagenesis of the cleavage sites of pro-CCK had profound
      effects on the products that were produced. Substitution of basic cleavage sites
      with nonbasic amino acids inhibits cleavage and leads to the secretion of pathway
      intermediates such as CCK-83, -33, and -12. These results suggest that CCK-58 is
      cleaved to both CCK-33 and -22. Furthermore, CCK-8 and -12 are likely derived
      from cleavage of CCK-33 but not CCK-22. Alanine substitution at the same site
      completely blocked production of amidated products, whereas serine substitution
      did not. The cleavages observed at nonbasic residues in this study may represent
      the activity of enzymes other than PC1 and carboxypeptidase E, such as the enzyme
      SKI-1. A model for the progression of pro-CCK processing in AtT-20 cells is
      proposed. The findings in this study further supports the hypothesis that pro-CCK
      undergoes parallel pathways of proteolytic cleavages.

PMID- 15260494
TI  - Structure-based design of Tet repressor to optimize a new inducer specificity.
AB  - We constructed a mutant of the tetracycline-inducible repressor protein TetR with
      specificity for the tc analogue 4-de(dimethylamino)anhydrotetracycline (4-ddma
      atc), which is neither an antibiotic nor an inducer for the wild-type protein.
      The previously published relaxed specificity mutant TetR H64K S135L displays
      reduced induction by tc but full induction by doxycycline (dox),
      anhydrotetracycline (atc), and 4-de(dimethylamino)-6-demethyl-6-deoxytetracycline
      (cmt3). To create induction specificity for tc derivatives lacking the 4
      dimethylamino grouping such as cmt3 and 4-ddma-atc, the residues at positions 82
      and 138, which are located close to that moiety in the crystal structure of the
      TetR-[tc-Mg](+)(2) complex, were randomized. We anticipated that a residue with
      increased size may lead to sterical hindrance, and screening for 4-ddma-atc
      specific induction indeed revealed the mutant TetR H64K S135L S138I. Out of 24
      exchanges only the addition of S138I to TetR H64K S135L yielded a mutant with a
      pronounced reduction of affinity for atc and dox, while the one for 4-ddma-atc is
      not affected. The ratio of binding constants revealed a 200-fold specificity
      increase for 4-ddma-atc over atc. The contributions of each single mutant to
      specificity indicate that the tc variants bind slightly different positions in
      the TetR tc binding pocket.

PMID- 15260495
TI  - Altered substrate specificity in flavocytochrome b2: structural insights into the
      mechanism of L-lactate dehydrogenation.
AB  - Flavocytochrome b(2) from Saccharomyces cerevisiae is a l-lactate/cytochrome c
      oxidoreductase belonging to a large family of 2-hydroxyacid-dependent
      flavoenzymes. The crystal structure of the enzyme, with pyruvate bound at the
      active site, has been determined [Xia, Z.-X., and Mathews, F. S. (1990) J. Mol.
      Biol. 212, 837-863]. The authors indicate that the methyl group of pyruvate is in
      close contact with Ala198 and Leu230. These two residues are not well-conserved
      throughout the family of (S)-2-hydroxy acid oxidases/dehydrogenases. Thus, to
      probe substrate specificity in flavocytochrome b(2), these residues have been
      substituted by glycine and alanine, respectively. Kinetic studies on the L230A
      mutant enzyme and the A198G/L230A double mutant enzyme indicate a change in
      substrate selectivity for the enzyme toward larger (S)-2-hydroxy acids. In
      particular, the L230A enzyme is more efficient at utilizing (S)-2
      hydroxyoctanoate by a factor of 40 as compared to the wild-type enzyme [Daff, S.,
      Manson, F. D. C., Reid, G. A., and Chapman, S. K. (1994) Biochem. J. 301, 829
      834], and the A198G/L230A double mutant enzyme is 6-fold more efficient with the
      aromatic substrate l-mandelate than it is with l-lactate [Sinclair, R., Reid, G.
      A., and Chapman, S. K. (1998) Biochem. J. 333, 117-120]. To complement these
      solution studies, we have solved the structure of the A198G/L230A enzyme in
      complex with pyruvate and as the FMN-sulfite adduct (both to 2.7 A resolution).
      We have also obtained the structure of the L230A mutant enzyme in complex with
      phenylglyoxylate (the product of mandelate oxidation) to 3.0 A resolution. These
      structures reveal the increased active-site volume available for binding larger
      substrates, while also confirming that the integrity of the interactions
      important for catalysis is maintained. In addition to this, the mode of binding
      of the bulky phenylglyoxylate at the active site is in accordance with the
      operation of a hydride transfer mechanism for substrate oxidation/flavin
      reduction in flavocytochrome b(2), whereas a mechanism involving the formation of
      a carbanion intermediate would appear to be sterically prohibited.

PMID- 15260496
TI  - Antimicrobial 14-helical beta-peptides: potent bilayer disrupting agents.
AB  - The interactions of two amphiphilic and cationic, nine-residue beta-peptides with
      liposomal membranes were studied. These beta-peptides are shown to form 14
      helices in the presence of bilayers. Membrane binding and membrane
      permeabilization occur preferentially in the presence of anionic lipids. The beta
      peptides have the ability to cause tranbilayer diffusion of phospholipids, form
      pores, and promote lipid mixing between liposomes. These beta-peptides have
      previously been shown to display antimicrobial activity comparable to that of a
      longer beta-peptide, beta-17, which adopts a different type of helical
      conformation (12-helix), and to the 23 amino acid (Ala(8,13,18))-magainin-II
      amide, which adopts an alpha-helical conformation. In addition, these 14-helical
      beta-peptides show relatively low hemolytic activity. The biological potency and
      microbial specificity of the 14-helical beta-peptides, despite their relatively
      short length, suggests that 14-helices can be particularly disruptive to
      microbial membranes.

PMID- 15260497
TI  - Salt-induced oligomerization of partially folded intermediates of equinatoxin II.
AB  - Equinatoxin II (EqTxII) is a cytolytic, water-soluble protein which binds to and
      forms cation-selective pores in lipid membranes. To characterize the native and
      denatured states of EqTxII and to elucidate the biological role of its oligomers,
      we have studied salt-dependent heat-induced conformational transitions of EqTxII.
      To this end, we have employed a variety of experimental techniques, including
      differential scanning calorimetry, circular dichroism and light absorption
      spectroscopy, ultrasonic velocimetry, electron microscopy, PAGE, and a hemolytic
      activity assay. This experimental combination has enabled us to monitor and
      structurally and thermodynamically characterize temperature-induced
      conformational transitions and oligomerization of EqTxII at different
      concentrations of NaCl. At pH 3.0 and 25 degrees C, EqTxII retains its native
      conformation and remains hemolytically active over a broad range of NaCl
      concentrations. However, an increase in the salt concentration results in a
      diminution of the thermal stability of EqTxII. Specifically, the calorimetrically
      determined denaturation temperature, T(d), and enthalpy, DeltaH(cal), of the
      toxin decrease with an increase in the salt concentration. Our CD data suggest
      that the heat-induced denatured state of EqTxII lacks rigid tertiary structure
      while exhibiting well-defined secondary structure. The amount of the induced, non
      native secondary structure of EqTxII depends on the solution ionic strength,
      temperature, time of incubation at an elevated temperature, and protein
      concentration. Our combined results suggest that, in the presence of salt, an
      increase in temperature results in formation of the partially unfolded state of
      the toxin that oligomerizes and forms biologically inactive, water-soluble
      aggregates.

PMID- 15260498
TI  - The acyltransferase homologue from the initiation module of the R1128 polyketide
      synthase is an acyl-ACP thioesterase that edits acetyl primer units.
AB  - Type II polyketide synthases (PKSs) synthesize polyfunctional aromatic
      polyketides through iterative condensations of malonyl extender units. The
      biosynthesis of most aromatic polyketides is initiated through an acetate unit
      derived from decarboxylation of malonyl-acyl carrier protein (ACP). Modification
      of this primer unit represents a powerful method of generating novel polyketides.
      We have demonstrated that recombination of the initiation module from the R1128
      PKS with heterologous elongation modules afforded regioselectively modified
      polyketides containing alternative primer units. With the exception of the role
      of the acyltransferase homologue ZhuC, the catalytic cycle of the initiation
      module has been well explored. ZhuC, along with the ketosynthase III homologue
      ZhuH and the ACP(p) ZhuG, is essential for the in vivo biosynthesis of aromatic
      polyketides derived from non-acetate primer units. Here we have studied the role
      of ZhuC using PKS proteins reconstituted in vitro. We show that the
      tetracenomycin (tcm) minimal PKS can be directly primed with non-acetate acyl
      groups. In the presence of approximately 10 microM hexanoyl-ZhuG or approximately
      100 microM hexanoyl-CoA, the tcm minimal PKS synthesized hexanoyl-primed
      analogues of octaketides SEK4 and SEK4b, as well as acetate-primed decaketides
      SEK15 and SEK15b at comparable levels. Addition of ZhuC abolished synthesis of
      the acetate-primed decaketides, resulting in exclusive synthesis of the hexanoyl
      primed octaketides. In the absence of alternative acyl donors, ZhuC severely
      retarded the activity of the tcm minimal PKS. The editing capabilities of ZhuC
      were directly revealed by demonstrating that ZhuC has 100 times greater
      specificity for acetyl- and propionyl-ACP as compared to hexanoyl- and octanoyl
      ACP. Thus, by purging the acetate primer units that otherwise dominate polyketide
      chain initiation, ZhuC (and presumably its homologues in other PKSs such as the
      doxorubicin and frenolicin PKSs) allows alternative primer units to be utilized
      by the elongation module in vivo. The abilities of other alkylacyl primer units
      to prime the tcm minimal PKS were also investigated in this report.

PMID- 15260499
TI  - Characterization of mutant xylanases using fourier transform ion cyclotron
      resonance mass spectrometry: stabilizing contributions of disulfide bridges and N
      terminal extensions.
AB  - Structural properties and thermal stability of Trichoderma reesei endo-1,4-beta
      xylanase II (TRX II) and its three recombinant mutants were characterized using
      electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR)
      mass spectrometry and hydrogen/deuterium (H/D) exchange reactions. TRX II has
      been previously stabilized by a disulfide bridge C110-C154 and other site
      directed mutations (TRX II mutants DS2 and DS5). Very recently, a highly
      thermostable mutant was introduced by combining mutations of DS5 with an N
      terminal disulfide bridge C2-C28 (mutant DB1). Accurate mass measurements of TRX
      II, DS2, DS5, and DB1 verified the expected DNA-encoded protein sequences
      (average mass error 1.3 ppm) and allowed unequivocal assignment of the disulfides
      without chemical reduction and subsequent alkylation of the expected cross-links.
      Moreover, H/D exchange reactions provided means for the detection of a major heat
      induced conformational change comprising two interconverting conformers of very
      different H/D exchange rates as well as allowed the apparent melting temperatures
      (T(m)) to be determined (62.6, 65.1, 68.0, and 82.2 degrees C for TRX II, DS2,
      DS5, and DB1, respectively). Residual activity measurements verified that the
      enzymes inactivated at significantly lower temperatures than expected on the
      basis of the apparent T(m) values, strongly suggesting that the inactivation
      takes place through minor conformational change other than observed by H/D
      exchange. ESI FT-ICR analyses also revealed molecular heterogeneity in DS5 and
      DB1 due to the propeptide incorporation. Resulting unintentional N-terminal
      extensions were observed to further improve the stability of the DB1 mutant. The
      extension of six amino acid residues upstream from the protein N-terminus
      increased stability by approximately 5 degrees C.

PMID- 15260500
TI  - Activation of the flavoprotein domain of gp91phox upon interaction with N
      terminal p67phox (1-210) and the Rac complex.
AB  - A series of truncated forms of His(6)-tagged gp91phox were expressed,
      solubilized, and purified in the presence of 30 microM FAD. The truncated
      gp91phox with the longest sequence in the C-terminal region (221-570) (gp91C)
      showed the highest activity (turnover rate, 0.92) for NADPH diaphorase in the
      presence of either 0.3% Triton X-100 or 0.5% Genapol X-80. Activity was not
      inhibited by superoxide dismutase but was blocked by an inhibitor of the
      respiratory burst oxidase, diphenylene iodonium. The flavinated gp91C contained
      approximately 0.9 mol of FAD/mol of protein (MW 46 kDa) and 12% alpha-helix
      content. In the absence of p47phox, p67phox showed considerable activation of
      gp91C in the presence of Rac. Carboxyl-terminal truncated p67phox (1-210) (p67N),
      which is the minimal active fragment, was fused with Rac or Q61LRac. The fusion
      protein p67N-Rac (or p67N-Q61LRac) showed a 2-fold higher stimulatory effect on
      NBT reductase activity of gp91C than the combination of the individual cytosolic
      p67N and Rac proteins. In contrast, Rac-p67N, a fusion with the opposite
      orientation, showed a smaller significant effect on the enzyme activity. The
      EC(50) values for p67phox, p67N, p67N-Rac, and Rac-p67N were 8.00. 4.35, 2.56,
      and 15.2 microM, respectively, while the K(m) value for NADPH in the presence and
      absence of the cytosolic components was almost the same (40-55 microM). In the
      presence of Rac, p67N or p67phox bound to gp91C with a molar ratio of
      approximately 1:1 but neither p67N nor Rac alone showed significant binding.

PMID- 15260501
TI  - Inhibition of mammalian RNA synthesis by the cytoplasmic Ca2+ buffer BAPTA.
      Analyses of [3H]uridine incorporation and stress-dependent transcription.
AB  - To determine whether oscillations of cytoplasmic [Ca(2+)] might be involved in
      transcription regulated by the unfolded protein response (UPR), dermal
      fibroblasts were loaded with the widely used Ca(2+) buffer BAPTA, which is
      expected to dampen cytoplasmic [Ca(2+)] changes without affecting resting
      [Ca(2+)]. BAPTA inhibited UPR-dependent transcription of the GRP78/BiP and EDEM
      genes. However, BAPTA also blocked cytoplasmic stress-dependent (UPR-independent)
      transcription of the HSP70 gene. These results led to the unexpected
      demonstration that BAPTA was a general inhibitor of cellular RNA synthesis in
      dermal fibroblasts. BAPTA is delivered to the cytoplasm as the acetoxymethyl (AM)
      ester BAPTA/AM, but released AM groups, as well as formaldehyde generated from AM
      breakdown, were ruled out as causes of RNA synthesis inhibition. BAPTA inhibited
      RNA synthesis in all mammalian cell types tested except CHO-K1. GRP78/BiP RNA
      induction in CHO-K1 cells was not blocked by BAPTA. Thus, there does not appear
      to be a critical requirement for cytoplasmic [Ca(2+)] changes in CHO-K1 UPR
      dependent transcription. However, general inhibition of RNA synthesis by the
      [Ca(2+)] buffer BAPTA was unanticipated. This might possibly reflect a fortuitous
      interaction of BAPTA with the RNA synthesis machinery or a requirement for
      [Ca(2+)] changes.

PMID- 15260502
TI  - The conversation continues I.

PMID- 15260503
TI  - The conversation continues II.

PMID- 15260504
TI  - Reactions of the diiron enzyme stearoyl-acyl carrier protein desaturase.
AB  - Stearoyl-acyl carrier protein Delta(9) desaturase (Delta9D) produces oleic acid,
      a nutritionally valuable fatty acid containing a cis double bond between C-9 and
      C-10. This multiprotein diiron enzyme complex reacts with stearoyl-acyl carrier
      protein, reduced [2Fe-2S] ferredoxin, and O(2) to complete the highly
      regiospecific and stereoselective desaturation reaction. Interactions with the
      acyl chain provide stability to the enzyme-substrate complex, give an energetic
      contribution to catalytic selectivity, and help to order the electron transfer,
      O(2) binding, and C-H bond cleavage steps of catalysis. Reactions with natural
      acyl chains indicate the involvement of a highly reactive diiron intermediate
      capable of oxidizing secondary C-H bonds (bond dissociation energy approximately
      95 kcal/mol), but also capable of diagnostic O-atom transfer reactions with the
      appropriate substrate analogues. For soluble Delta9D, the natural reaction may
      initiate at the C-10 position, in contrast to the well-established initial
      reactivity of the membrane enzyme homologue stearoyl-coenzyme A (CoA) Delta(9)
      desaturase at the C-9 position.

PMID- 15260505
TI  - Role of glycosaminoglycans in cellular communication.
AB  - Glycosaminoglycans are of critical importance in intercellular communication in
      organisms. This ubiquitous class of linear polyanions interacts with a wide
      variety of proteins, including growth factors and chemokines, which regulate
      important physiological processes. The presence of glycosaminoglycans on cell
      membranes and in the extracellular matrix also has resulted in their exploitation
      by infectious pathogens to gain access and entry into animal cells. This Account
      examines the structural and physical characteristics of these molecules
      responsible for their interaction with proteins important in cell-cell
      communication.

PMID- 15260506
TI  - Metal ion modulated electron transfer in photosynthetic proteins.
AB  - Photosynthetic purple bacterial reaction center (RC) proteins are ideal native
      systems for addressing basic questions regarding the nature of biological
      electron transfer because both the protein structure and the electron-transfer
      reactions are well-characterized. Metal ion binding to the RC can affect primary
      photochemistry and provides a probe for understanding the involvement of local
      protein environments in electron transfer. The RC has two distinct transition
      metal ion binding sites, the well-known non-heme Fe(2+) site buried in the
      protein interior and a recently discovered Zn(2+) site located on the surface of
      the protein. Fe(2+) removal and Zn(2+) binding systematically affect different
      electron-transfer steps in the RC. Factors involved in the metal ion alteration
      of RC electron transfer may provide a paradigm for other biological systems
      involved in electron transfer.

PMID- 15260507
TI  - Origin, control, and application of supramolecular chirogenesis in bisporphyrin
      based systems.
AB  - The rationalization of various aspects of the mechanism of chirality induction in
      supramolecular assemblies based upon the complexes formed between an ethane
      linked bisoctaethylporphyrin and chiral ligands is described. The influence of
      various controlling factors such as bonding strength, host-guest steric
      interactions, equilibria and thermodynamic parameters, temperature and solvent
      effects, role of the center metal ion, stoichiometry, and phase transition on the
      chirality induction processes have been investigated, and the results and
      implications are discussed. As a result of such detailed understanding, it is
      possible to employ this bisporphyrin system as an effective chirality sensor for
      the determination of absolute configuration.

PMID- 15260508
TI  - Combined spectroscopic/computational studies on Fe- and Mn-dependent superoxide
      dismutases: insights into second-sphere tuning of active site properties.
AB  - Superoxide dismutases (SODs) are metalloenzymes that protect aerobic organisms
      from oxidative damage mediated by the superoxide radical. While the Fe- and Mn
      dependent SODs from E. coli possess virtually identical protein folds and active
      site geometries, they are strictly metal specific. To explore the origin of this
      extraordinary metal-ion specificity and to elucidate the mechanisms by which
      these enzymes tune the geometric and electronic properties, and thus the
      reactivity, of their active-site metal ions, we utilized a combination of
      spectroscopic and computational methods to study the native enzymes, their metal
      substituted derivatives, and several mutant proteins. Results from our research
      described in this Account reveal that second-sphere residues are critically
      involved in controlling both thermodynamic and kinetic properties of the Fe- and
      MnSOD active sites.

PMID- 15260509
TI  - Determining the geometries of transition States by use of antihydrophobic
      additives in water.
AB  - The quantitative effect of cosolvents on the water solubility of hydrophobic
      substrates can be correlated with the effect on reaction rates to determine the
      geometries of transition states for Diels-Alder reactions, the benzoin
      condensation, and alkylations of phenoxide ions and aniline. Some of these
      reactions have transition states with packing of hydrophobic surfaces and some do
      not. Methods were devised to sort out the effect of the cosolvents on solvation
      of hydrophobic surfaces and the effect on solvation of polar groups. The result
      is a set of geometries for these reactions that is consistent with theory.

PMID- 15260510
TI  - Progress in the chemistry of metallabenzynes.
AB  - The synthesis and chemical and structural properties of metallabenzynes are
      reviewed. Reaction of [OsCl(2)(PPh(3))(3)] with HC(triple bonded)CSiMe(3)
      produces the osmabenzyne [Os((triple
      bonded)CC(SiMe(3))=C(CH(3))C(SiMe(3))=CH)Cl(2)(PPh(3))(2)], which undergoes
      electrophilic substitution reactions with HBF(4) and Br(2) to give new
      osmabenzynes. The reactivities and the X-ray diffraction data of osmabenzynes
      indicate that these metallacycles have aromatic properties. Unlike benzyne, which
      is thermally unstable, osmabenzynes are thermally much more stable and can be
      stored for months at room temperature without decomposition. The higher thermal
      stability of osmabenzynes compared to benzyne can be related to the relatively
      smaller ring strain and larger conjugation energy.

PMID- 15260511
TI  - Future options for combination therapy in the management of erectile dysfunction
      in older men.
AB  - The prevalence of erectile dysfunction (ED) has dramatically increased in
      parallel with the aging of the Western industrialised population. The estimated
      prevalence of ED worldwide in 1995 was 152 million men. As the population in
      industrial nations ages, an estimated 322 million men will be affected by ED by
      the year 2025. Oral drug therapy with the phosphodiesterase (PDE) type 5
      inhibitor sildenafil fails in some patients with ED; however, several different
      classes of drugs demonstrate efficacy in treating ED, creating the potential for
      pharmacological combination therapy. Pharmaceutical products that lead to the
      activation of or an increase in cyclic nucleotides (cyclic adenosine
      monophosphate and cyclic guanosine monophosphate), with or without nitric oxide
      donors or nitrates, as well as alpha-adrenoceptor antagonists, have been used to
      treat ED. Sildenafil has been used in combination with alprostadil (prostaglandin
      E1) and administered via intraurethral or intracavernous route. Successful
      intercourse using this combination of agents varies from 47% to 100% following
      failed monotherapy. Various combination therapies for ED are being studied using
      PDE5 inhibitors, together with other agents, alpha-adrenoceptor antagonists, and
      testosterone replacement therapy for men with hypogonadism. The combination of
      centrally acting agents with PDE5 inhibitors, e.g. a regimen of apomorphine plus
      PDE5 inhibitor, is an attractive approach because the two therapies target
      different mechanisms. New PDE5 inhibitors such as vardenafil should be tried
      first as therapy for sildenafil nonresponders before exploring any combination
      therapy options. Preliminary observations of combination therapy have been
      encouraging and provide a scientific rationale for prospective, randomised
      clinical trials with adequate numbers of patients.

PMID- 15260512
TI  - Use of calcium channel antagonists for the treatment of hypertension in the
      elderly.
AB  - Systolic blood pressure and pulse pressure increase continuously throughout adult
      life and the prevalence of arterial hypertension rises accordingly, reaching 53
      78% among those aged 65-74 years. Estimates of the prevalence of isolated
      systolic hypertension in the elderly range from 34-65%, with more women than men
      affected. It has been shown that within all age groups a difference in usual
      systolic blood pressure of 20 mm Hg or a difference in usual diastolic blood
      pressure of 10 mm Hg is associated with an approximately 2-fold difference in the
      risk of dying from stroke or ischaemic heart disease. Intervention trials using
      predominantly diuretics and/or beta-adrenoceptor antagonists have proven the
      efficacy and tolerability of antihypertensive treatment in elderly patients. For
      many years there have been ongoing discussions about the safety of calcium
      channel antagonists, especially in patients with diabetes mellitus. However,
      according to a recently published large prospective, randomised, double-blind,
      controlled clinical trial with more than 33,000 patients enrolled, no indications
      for increased total mortality, cancer rate or gastrointestinal bleeding for
      participants on amlodipine, a long-acting dihydropyridine calcium channel
      antagonist, were found. With calcium channel antagonists, protective effects
      against cardiovascular disease have been proven in large trials with elderly
      patients, particularly against stroke. There is good evidence to suggest that
      calcium channel antagonists may be superior to other antihypertensive agents in
      diabetic patients with isolated systolic hypertension. These agents are well
      tolerated and probably delay the progression of dementia. The lack of adverse
      metabolic effects that, in the case of a diuretic-based regimen, may have
      important long-term implications concerning cardiovascular risk, make calcium
      channel antagonists an attractive choice when antihypertensive treatment
      decisions need to be made in a predominantly overweight or obese elderly
      population.

PMID- 15260513
TI  - Strategies to increase HMG-CoA reductase inhibitor use after acute myocardial
      infarction.
AB  - Coronary artery disease with its accompanying complication of acute myocardial
      infarction (MI) is one of the major causes of death in the modern world. A
      variety of both primary and secondary prevention strategies have been developed
      for the treatment of acute MI. One of the more important of these strategies is
      the prescription of HMG-CoA reductase inhibitors. HMG-CoA reductase inhibitors
      have the potential to positively affect the outcome of acute MI in a variety of
      ways including the reduction of low-density lipoprotein-cholesterol levels and
      stabilisation of the atherosclerotic plaque. Multiple large randomised clinical
      trials have documented the potential of HMG-CoA reductase inhibitors to reduce
      both short- and long-term mortality after acute MI. This benefit exists
      regardless of age, gender, clinical presentation, or even baseline lipid levels.
      However, despite this overwhelming amount of evidence supporting the use of HMG
      CoA reductase inhibitors in the post-MI setting, multiple studies have documented
      the presence of a significant 'treatment gap'. Indeed, often, less than half of
      acute MI patients who would benefit from HMG-CoA reductase inhibitor therapy
      actually receive it. The reasons for the low utilisation of HMG-CoA reductase
      inhibitors in the acute MI patient are many, but may include poor communication,
      the high cost of treatment, the lack of associated symptoms and confusion
      regarding appropriate lipid levels to target. One approach that has been tried to
      address these issues is the development of institutional programmes specifically
      targeted to increase the use of HMG-CoA reductase inhibitors in acute MI
      patients. These programmes, often managed by nurses or pharmacists, have been
      piloted in several institutions. They have been effectively implemented in both
      inpatient and outpatient settings. In most cases they have been implemented
      without a great increase in expense. They have often increased the use of HMG-CoA
      reductase inhibitors to >90%. Most importantly, they have documented a
      significant improvement in the long-term survival of acute MI patients. Based on
      these preliminary studies, it is recommended that the implementation of these
      strategies be considered by most healthcare institutions.

PMID- 15260514
TI  - Herbal supplement use by persons aged over 50 years in Britain: frequently used
      herbs, concomitant use of herbs, nutritional supplements and prescription drugs,
      rate of informing doctors and potential for negative interactions.
AB  - BACKGROUND: The use of herbal and nutritional supplements by older British people
      is increasing and despite the risks of adverse effects and negative herb-drug
      interactions, doctors are often not informed of their use. The number of herbal
      and nutritional supplements used most frequently by older people, and which
      particular herbal extracts are used, are unknown. This study aimed to identify
      how many herbal and nutritional supplements and which herbal extracts are most
      frequently used by British people >50 years of age, and to identify which herb
      drug interactions represent the greatest risk to this age group. METHOD: A self
      completed survey was promoted through websites and a popular magazine aimed at
      people >50 years of age. RESULTS: Respondents (n = 271) used a mean of 2.26
      prescription drugs and 5.91 herbal and nutritional supplements, including 2.66
      herbal extracts. The use of herbal medicines by older British people frequently
      involves the use of several herbs, often involves concomitant use with several
      nutritional supplements, is poorly reported to doctors and places older people at
      risk of negative herb-drug interactions. The most frequently used herbs and
      associated risks of negative interactions with prescription drugs are identified.
      CONCLUSIONS: Older people should be encouraged to report the use of herbs and
      nutritional supplements to their doctors, and doctors should be provided with
      comprehensive and up-to-date information about potential herb-drug interactions.

PMID- 15260515
TI  - Cost effectiveness of memantine in Alzheimer's disease: an analysis based on a
      probabilistic Markov model from a UK perspective.
AB  - BACKGROUND: Clinical trials with memantine, an uncompetitive moderate-affinity
      NMDA antagonist, have shown improved clinical outcomes, increased independence
      and a trend towards delayed institutionalisation in patients with moderately
      severe-to-severe Alzheimer's disease. In a randomised double-blind, placebo
      controlled, 28-week study conducted in the US, reductions in resource utilisation
      and total healthcare costs were noted with memantine relative to placebo. While
      these findings suggest that, compared with placebo, memantine provides cost
      savings, further analyses may help to quantify potential economic gains over a
      longer treatment period. OBJECTIVE: To evaluate the cost effectiveness of
      memantine therapy compared with no pharmacological treatment in patients with
      moderately severe-to-severe Alzheimer's disease over a 2-year period. METHODS: A
      Markov model was constructed to simulate patient progression through a series of
      health states related to severity, dependency (determined by patient scores on
      the Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]
      inventory and residential status ('institutionalisation') with a time horizon of
      2 years (each 6-month Markov cycle was repeated four times). Transition
      probabilities from one health state to another 6 months later were mainly derived
      from a 28-week, randomised, double-blind, placebo-controlled clinical trial.
      Inputs related to epidemiological and cost data were derived from a UK
      longitudinal epidemiological study, while data on quality-adjusted life-years
      (QALYs) were derived from a Danish longitudinal study. To ensure conservative
      estimates from the model, the base case analysis assumed drug effectiveness was
      limited to 12 months. Monte Carlo simulations were performed for each state
      parameter following definition of a priori distributions for the main variables
      of the model. Sensitivity analyses included worst case scenario in which
      memantine was effective for 6 months and one-way sensitivity analyses on key
      parameters. Finally, a subgroup analysis was performed to determine which
      patients were most likely to benefit from memantine. Informal care was not
      included in this model as the costs were considered from National Health Service
      and Personal Social Services perspective. RESULTS: The base case analysis found
      that, compared with no treatment, memantine was associated with lower costs and
      greater clinical effectiveness in terms of years of independence, years in the
      community and QALYs. Sensitivity analyses supported these findings. For each
      category of Alzheimer's disease patient examined, treatment with memantine was a
      cost-effective strategy. The greatest economic gain of memantine treatment was in
      independent patients with a Mini-Mental State Examination score of > or =10.
      CONCLUSION: This model suggests that memantine treatment is cost effective and
      provides cost savings compared with no pharmacological treatment. These benefits
      appear to result from prolonged patient independence and delayed
      institutionalisation for moderately severe and severe Alzheimer's disease
      patients on memantine compared with no pharmacological treatment.

PMID- 15260516
TI  - A regression technique to analyze the second-order nonlinear optical response of
      thin films.
AB  - We present a new technique, based on regression analysis, to determine the second
      order nonlinear optical susceptibility tensor of thin films. The technique does
      not require the absolute levels or phases of measured signals to be mutually
      calibrated. In addition it yields indicators that address the quality of
      theoretical models describing the sample. We use the technique to determine the
      susceptibility tensor of samples of a nonracemic chiral material which have very
      low symmetry (both chiral and anisotropic) and have many independent tensor
      components. The results show the importance of using detailed theoretical models
      that account for the linear optical properties of the sample.

PMID- 15260517
TI  - Jahn-Teller effect for short-lived states: study of the complex potential energy
      surfaces.
AB  - The Jahn-Teller effect for bound electronic states has been investigated for many
      decades. In contrast, nothing is known regarding its occurrence for short-lived
      electronic states. Here we investigate the linear and the quadratic E multiply x
      e Jahn-Teller effect for degenerate resonance states with special regard to the
      complex potential energy surfaces. We find many new phenomena for both the real
      and imaginary parts of the potential energy surfaces including additional minima
      and intersections. Possible simplifications of the equations describing the
      adiabatic potential energy surfaces are discussed. We also briefly investigate
      other Jahn-Teller effects in linear approximation. The theoretical concepts are
      exemplified by calculating ab initio data for the degenerate Pi(*)-type resonance
      states of the tris(boramethyl)amin anion along two different doubly degenerate
      vibrational modes.

PMID- 15260518
TI  - The trust-region self-consistent field method: towards a black-box optimization
      in Hartree-Fock and Kohn-Sham theories.
AB  - The trust-region self-consistent field (TRSCF) method is presented for optimizing
      the total energy E(SCF) of Hartree-Fock theory and Kohn-Sham density-functional
      theory. In the TRSCF method, both the Fock/Kohn-Sham matrix diagonalization step
      to obtain a new density matrix and the step to determine the optimal density
      matrix in the subspace of the density matrices of the preceding diagonalization
      steps have been improved. The improvements follow from the recognition that local
      models to E(SCF) may be introduced by carrying out a Taylor expansion of the
      energy about the current density matrix. At the point of expansion, the local
      models have the same gradient as E(SCF) but only an approximate Hessian. The
      local models are therefore valid only in a restricted region-the trust region-and
      steps can only be taken with confidence within this region. By restricting the
      steps of the TRSCF model to be inside the trust region, a monotonic and
      significant reduction of the total energy is ensured in each iteration of the
      TRSCF method. Examples are given where the TRSCF method converges monotonically
      and smoothly, but where the standard DIIS method diverges.

PMID- 15260519
TI  - Excitation energies from time-dependent density-functional theory beyond the
      adiabatic approximation.
AB  - Time-dependent density-functional theory in the adiabatic approximation has been
      very successful for calculating excitation energies in molecular systems. This
      paper studies nonadiabatic effects for excitation energies, using the current
      density functional of Vignale and Kohn [Phys. Rev. Lett. 77, 2037 (1996)]. We
      derive a general analytic expression for nonadiabatic corrections to excitation
      energies of finite systems and calculate singlet s-->s and s-->p excitations of
      closed-shell atoms. The approach works well for s-->s excitations, giving a small
      improvement over the adiabatic local-density approximation, but tends to
      overcorrect s-->p excitations. We find that the observed problems with the
      nonadiabatic correction have two main sources: (1) the currents associated with
      the s-->p excitations are highly nonuniform and, in particular, change direction
      between atomic shells, (2) the so-called exchange-correlation kernels of the
      homogeneous electron gas, f(xc) (L) and f(xc) (T), are incompletely known, in
      particular in the high-density atomic core regions.

PMID- 15260520
TI  - All-forward semiclassical simulations of nonlinear response functions.
AB  - We propose a quantum trajectory algorithm for computing nonlinear response
      functions of condensed phase molecular systems based on a time-ordered expansion
      of the density matrix. The nth-order response function is expressed as a sum of
      2(n) impulsive response pathways representing trajectories involving zero, one,
      and up to n interactions with short external pulses. These are evaluated using a
      forward propagation algorithm based upon a Liouville space extension of the
      Bohmian propagation method.

PMID- 15260521
TI  - Multiple "time step" Monte Carlo simulations: application to charged systems with
      Ewald summation.
AB  - Recently, we have proposed an efficient scheme for Monte Carlo simulations, the
      multiple "time step" Monte Carlo (MTS-MC) [J. Chem. Phys. 117, 8203 (2002)] based
      on the separation of the potential interactions into two additive parts. In this
      paper, the structural and thermodynamic properties of the simple point charge
      water model combined with the Ewald sum are compared for the MTS-MC real
      /reciprocal-space split of the Ewald summation and the common Metropolis Monte
      Carlo method. We report a number of observables as a function of CPU time
      calculated using MC and MTS-MC. The correlation functions indicate that speedups
      on the order of 4.5-7.5 can be obtained for systems of 108-500 waters for n=10
      splitting parameter.

PMID- 15260522
TI  - Higher-order equation-of-motion coupled-cluster methods.
AB  - The equation-of-motion coupled-cluster (EOM-CC) methods truncated after double,
      triple, or quadruple cluster and linear excitation operators (EOM-CCSD, EOM
      CCSDT, and EOM-CCSDTQ) have been derived and implemented into parallel execution
      programs. They compute excitation energies, excited-state dipole moments, and
      transition moments of closed- and open-shell systems, taking advantage of spin,
      spatial (real Abelian), and permutation symmetries simultaneously and fully
      (within the spin-orbital formalisms). The related Lambda equation solvers for
      coupled-cluster (CC) methods through and up to connected quadruple excitation
      (CCSD, CCSDT, and CCSDTQ) have also been developed. These developments have been
      achieved, by virtue of the algebraic and symbolic manipulation program that
      automated the formula derivation and implementation altogether. The EOM-CC
      methods and CC Lambda equations introduce a class of second quantized ansatz with
      a de-excitation operator (Y), a number of excitation operators (X), and a
      physical (e.g., the Hamiltonian) operator (A), leading to the tensor contraction
      expressions that can be performed in the order of ((...((yx)x)...)x)a or
      ((...((ax)x)...)x)y at the minimal peak operation cost, where x, y, and a are
      basis-set representations (i.e., tensors) of the respective operators X, Y, and
      A. Any intermediate tensor resulting from either contraction order is shown to
      have at most six groups of permutable indices, and this knowledge is used to
      guide the computer-synthesized programs to fully exploit the permutation symmetry
      of any tensor to minimize the arithmetic and memory costs.

PMID- 15260523
TI  - Accurate energetics of small molecules containing third-row atoms Ga-Kr: a
      comparison of advanced ab initio and density functional theory.
AB  - Advanced ab initio [coupled cluster theory through quasiperturbative triple
      excitations (CCSD(T))] and density functional (B3LYP) computational chemistry
      approaches were used in combination with the standard and augmented correlation
      consistent polarized valence basis sets [cc-pVnZ and aug-cc-pVnZ, where n=D(2),
      T(3), Q(4), and 5] to investigate the energetic and structural properties of
      small molecules containing third-row (Ga-Kr) atoms. These molecules were taken
      from the Gaussian-2 (G2) extended test set for third-row atoms. Several different
      schemes were used to extrapolate the calculated energies to the complete basis
      set (CBS) limit for CCSD(T) and the Kohn-Sham (KS) limit for B3LYP. Zero point
      energy and spin orbital corrections were included in the results. Overall,
      CCSD(T) atomization energies, ionization energies, proton affinities, and
      electron affinities are in good agreement with experiment, within 1.1 kcal/mol
      when the CBS limit has been determined using a series of two basis sets of at
      least triple zeta quality. For B3LYP, the overall mean absolute deviation from
      experiment for the three properties and the series of molecules is more
      significant at the KS limit, within 2.3 and 2.6 kcal/mol for the cc-pVnZ and aug
      cc-pVnZ basis set series, respectively.

PMID- 15260524
TI  - Extracting dominant pair correlations from many-body wave functions.
AB  - The singular value decomposition of the n-particle excitation operator as
      determined by coupled cluster or perturbation theory is used to extract the
      dominant and interesting electron-electron correlations from complex molecular
      wave functions. As an example of the very general formalism, the decomposition of
      the T(2) operator obtained from coupled cluster doubles calculations is used to
      analyze the strength and character of pair correlations in a variety of molecules
      with interesting electronic structure. The magnitude of the largest singular
      value(s) determines the strength of the correlation(s), and the corresponding
      right- and left-hand singular vectors characterize the physical and spatial
      nature of the correlations. The primary advantage of this tool over natural
      orbital analysis is that it provides direct associations between the occupied and
      virtual geminals involved in the correlations.

PMID- 15260525
TI  - Reaction path potential for complex systems derived from combined ab initio
      quantum mechanical and molecular mechanical calculations.
AB  - Combined ab initio quantum mechanical and molecular mechanical calculations have
      been widely used for modeling chemical reactions in complex systems such as
      enzymes, with most applications being based on the determination of a minimum
      energy path connecting the reactant through the transition state to the product
      in the enzyme environment. However, statistical mechanics sampling and reaction
      dynamics calculations with a combined ab initio quantum mechanical (QM) and
      molecular mechanical (MM) potential are still not feasible because of the
      computational costs associated mainly with the ab initio quantum mechanical
      calculations for the QM subsystem. To address this issue, a reaction path
      potential energy surface is developed here for statistical mechanics and dynamics
      simulation of chemical reactions in enzymes and other complex systems. The
      reaction path potential follows the ideas from the reaction path Hamiltonian of
      Miller, Handy and Adams for gas phase chemical reactions but is designed
      specifically for large systems that are described with combined ab initio quantum
      mechanical and molecular mechanical methods. The reaction path potential is an
      analytical energy expression of the combined quantum mechanical and molecular
      mechanical potential energy along the minimum energy path. An expansion around
      the minimum energy path is made in both the nuclear and the electronic degrees of
      freedom for the QM subsystem internal energy, while the energy of the subsystem
      described with MM remains unchanged from that in the combined quantum mechanical
      and molecular mechanical expression and the electrostatic interaction between the
      QM and MM subsystems is described as the interaction of the MM charges with the
      QM charges. The QM charges are polarizable in response to the changes in both the
      MM and the QM degrees of freedom through a new response kernel developed in the
      present work. The input data for constructing the reaction path potential are
      energies, vibrational frequencies, and electron density response properties of
      the QM subsystem along the minimum energy path, all of which can be obtained from
      the combined quantum mechanical and molecular mechanical calculations. Once
      constructed, it costs much less for its evaluation. Thus, the reaction path
      potential provides a potential energy surface for rigorous statistical mechanics
      and reaction dynamics calculations of complex systems. As an example, the method
      is applied to the statistical mechanical calculations for the potential of mean
      force of the chemical reaction in triosephosphate isomerase.

PMID- 15260526
TI  - Transmission coefficient calculation for proton transfer in triosephosphate
      isomerase based on the reaction path potential method.
AB  - A global potential energy surface has been constructed through interpolation of
      our recently developed reaction path potential for chemical reactions in enzymes
      which is derived from combined ab initio quantum mechanical and molecular
      mechanical calculations. It has been implemented for the activated molecular
      dynamics simulations of the initial proton transfer reaction catalyzed by
      triosephosphate isomerase. To examine the dynamical effects on the rate constants
      of the enzymatic reaction, the classical transmission coefficient kappa(t) is
      evaluated to be 0.47 with the reactive flux approach, demonstrating considerable
      deviations from transition state theory. In addition, the fluctuations of protein
      environments have small effects on the barrier recrossing, and the transmission
      coefficient kappa(t) strongly depends on the fluctuations of atoms near the
      active site of the enzyme.

PMID- 15260527
TI  - The canonical ensemble via symplectic integrators using Nose and Nose-Poincare
      chains.
AB  - Simulations that sample from the canonical ensemble can be generated by the
      addition of a single degree of freedom, provided that the system is ergodic, as
      described by Nose with subsequent modifications by Hoover to allow sampling in
      real time. Nose-Hoover dynamics is not ergodic for small or stiff systems and the
      addition of auxiliary thermostats is needed to overcome this deficiency. Nose
      Hoover dynamics, like its derivatives, does not have a Hamiltonian structure,
      precluding the use of symplectic integrators which are noted for their long term
      stability and structure preservation. As an alternative to Nose-Hoover, the
      Hamiltonian Nose-Poincare method was proposed by Bond, Laird, and Leimkuhler [J.
      Comput. Phys. 151, 114 (1999)], but the straightforward addition of
      thermostatting chains does not sample from the canonical ensemble. In this paper
      a method is proposed whereby additional thermostats can be applied to a
      Hamiltonian system while retaining sampling from the canonical ensemble. This
      technique has been used to construct thermostatting chains for the Nose and Nose
      Poincare methods.

PMID- 15260528
TI  - Explicitly correlated second order perturbation theory: introduction of a
      rational generator and numerical quadratures.
AB  - A rational generator, which fulfills the cusp conditions for singlet and triplet
      electron pairs, is proposed and applied to explicitly correlated second order
      Moller-Plesset perturbation theory calculations. It is shown that the generator
      in conjunction with frozen geminals improves the convergence of correlation
      energy without introducing any variational parameters in explicitly correlated
      functions. A new scheme for three-electron integrals based on numerical
      quadratures is also illustrated. The method is tested for the convergence of
      reaction enthalpies with various basis sets.

PMID- 15260529
TI  - Ab initio prediction of the potential energy surface and vibrational-rotational
      energy levels of dialuminum monoxide, Al2O.
AB  - The equilibrium structure and potential energy surface of dialuminum monoxide,
      Al(2)O, have been determined from large-scale ab initio calculations using the
      coupled-cluster method, CCSD(T), in conjunction with basis sets of triple-
      through quintuple-zeta quality. The effects of core-electron correlation on the
      calculated molecular parameters were investigated. The vibrational-rotational
      energy levels of the Al(2) (16)O and Al(2) (18)O isotopic species were calculated
      by a variational approach. The predicted energy levels are in remarkably good
      agreement with the available experimental spectroscopic data (from laser-induced
      fluorescence), demonstrating that the Al(2)O molecule is linear at equilibrium in
      its ground electronic state. The reported theoretical data settle controversies
      between the experimental studies about the equilibrium structure and assignment
      of vibrational fundamentals of the Al(2)O molecule.

PMID- 15260530
TI  - Resonance coupling in the fourth OH-stretching overtone spectrum of formic acid.
AB  - The room-temperature vibrational overtone spectra of the formic acid isotopomers
      HCOOH and DCOOH have been recorded in the third and fourth OH-stretching overtone
      regions with intracavity laser photoacoustic spectroscopy. Resonance coupling
      between the OH- and CH-stretching vibrations in HCOOH is clearly identified in
      the fourth overtone region. This is an example of strong coupling across bonds.
      In the third overtone region, no resonance is observed. Vibrational energies and
      intensities of the OH- and CH-stretching overtones and combination bands have
      been calculated with an anharmonic oscillator local mode model. The pure OH
      stretching bright state carries almost all the intensity prior to resonance
      coupling.

PMID- 15260531
TI  - An ab initio correlated study of the potential energy surface for the HOBr.H2O
      complex.
AB  - The potential energy surface (PES) for the HOBr.H(2)O complex has been
      investigated using second- and fourth-order Moller-Plesset perturbation theory
      (MP2, MP4) and coupled cluster theory with single and doubles excitations (CCSD),
      and a perturbative approximation of triple excitations (CCSD-T), correlated ab
      initio levels of theory employing basis sets of triple zeta quality with
      polarization and diffuse functions up to the 6-311++G(3dp,3df ) standard Pople's
      basis set. Six stationary points being three minima, two first-order transition
      state (TS) structures and one second-order TS were located on the PES. The global
      minimum syn and the anti equilibrium structure are virtually degenerated
      [DeltaE(ele-nuc) approximately 0.3 kcal mol(-1), CCSD-T/6-311++G(3df,3pd) value],
      with the third minima being approximately 4 kcal mol(-1) away. IRC analysis was
      performed to confirm the correct connectivity of the two first-order TS
      structures. The CCSD-T/6-311++G(3df,3pd)//MP2/6-311G(d,p) barrier for the syn<-
      >anti interconversion is 0.3 kcal mol(-1), indicating that a mixture of the syn
      and anti forms of the HOBr.H(2)O complex is likely to exist.

PMID- 15260532
TI  - Two-color resonance-enhanced multiphoton ionization study of the lowest Rydberg p
      state of bis(eta6-benzene)chromium and its deuterated derivatives.
AB  - Two-color resonance-enhanced multiphoton ionization (REMPI) spectra of jet-cooled
      (eta(6)-C(6)H(6))(2)Cr(1), (eta(6)-C(6)D(6))(2)Cr(2), and (eta(6)
      C(6)D(6))(eta(6)-C(6)D(5)H)Cr(3) have been measured with use of the 3d(z)2-
      >R4p(x,y) Rydberg transition as the first step of the electronic excitation. The
      0(0) (0) Rydberg component shifts by 59 and 54 cm(-1) to red when one goes from 1
      to 2 and 3, respectively. Surprisingly, the REMPI spectra of 1-3 show very rich
      vibronic structures revealing both totally symmetric vibrations and degenerate
      vibrational modes. Presence of intense peaks corresponding to the e(2g) modes in
      the spectra of 1 and 2 is indicative of Jahn-Teller coupling in the R4p(x,y)
      Rydberg state. Additional REMPI resonances appear on going from 1 and 2 to 3 as a
      result of the symmetry reduction. The vibronic components in the spectra of 1-3
      were assigned on the basis of the selection rules and comparison with the
      vibrational frequencies of the 1 and 2 ground-state molecules. The frequencies of
      over 10 normal vibrations have been determined for the gas-phase 1-3 Rydberg
      state molecules from the REMPI experiment. The wavenumber corresponding to the
      lowest-energy mode (the ring torsion vibration) appears to be 40 cm(-1) in 1 and
      35 cm(-1) in the deuterated complexes. The REMPI peaks are homogeneously
      broadened. The lower lifetime limits for the upper-state components increase on
      going from the vibrationless level to higher-lying vibronic states and on going
      from 1 to the deuterated derivatives.

PMID- 15260533
TI  - The permanent dipole moment of gas-phase para-amino benzoic acid revisited.
AB  - The permanent dipole moment of para-amino benzoic acid has been calculated at
      various theoretical levels, including Hartree-Fock, second-order Moller-Plesset
      perturbation (MP2), coupled cluster singles and doubles (CCSD), and triples
      corrections CCSD(T), and hybrid density functional theory at B3LYP level. It is
      found that the B3LYP method fails to provide correct results for the geometry and
      the permanent dipole moment. These results are significantly improved by MP2
      calculations. Our best estimated dipole moments obtained at CCSD and CCSD(T)
      levels are in good agreement with experiment.

PMID- 15260534
TI  - Perturbation analysis for the rotational spectrum of the NiBr radical in the
      X2Pi3/2 and A2Delta5/2 states.
AB  - The millimeter- and submillimeter-wave spectra of the NiBr radical in the X
      (2)Pi(3/2) and A (2)Delta(5/2) states were observed by a source-modulated
      microwave spectrometer. The NiBr radical was generated in a dc glow discharge
      through the mixture of Br(2) vapor and Ar gas by the sputtering reaction with a
      Ni cathode. Observed transition frequencies were independently analyzed for both
      electronic states using a standard polynomial expression of a Hund's case (c)
      approximation. Anomalous behavior of the effective molecular constants in the X
      (2)Pi(3/2) state was interpreted as the result of the perturbation between the X
      (2)Pi(3/2) and A (2)Delta(5/2) states. The deperturbed molecular constants were
      derived using a simplified supermultiplet Hamiltonian including the interaction
      terms between the two electronic states.

PMID- 15260535
TI  - The role of angular momentum in collision-induced vibration-rotation relaxation
      in polyatomics.
AB  - Vibrational relaxation of the 6(1) level of S(1)((1)B(2u)) benzene is analyzed
      using the angular momentum model of inelastic processes. Momentum-(rotational)
      angular momentum diagrams illustrate energetic and angular momentum constraints
      on the disposal of released energy and the effect of collision partner on
      resultant benzene rotational excitation. A kinematic "equivalent rotor" model is
      introduced that allows quantitative prediction of rotational distributions from
      inelastic collisions in polyatomic molecules. The method was tested by predicting
      K-state distributions in glyoxal-Ne as well as J-state distributions in
      rotationally inelastic acetylene-He collisions before being used to predict J and
      K distributions from vibrational relaxation of 6(1) benzene by H(2), D(2), and
      CH(4). Diagrammatic methods and calculations illustrate changes resulting from
      simultaneous collision partner excitation, a particularly effective mechanism in
      p-H(2) where some 70% of the available 6(1)-->0(0) energy may be disposed into 0-
      >2 rotation. These results support the explanation for branching ratios in 6(1)-
      >0(0) relaxation given by Waclawik and Lawrance and the absence of this pathway
      for monatomic partners. Collision-induced vibrational relaxation in molecules
      represents competition between the magnitude of the energy gap of a potential
      transition and the ability of the colliding species to generate the angular
      momentum (rotational and orbital) needed for the transition to proceed.
      Transition probability falls rapidly as DeltaJ increases and for a given molecule
      collision partner pair will provide a limit to the gap that may be bridged.
      Energy constraints increase as collision partner mass increases, an effect that
      is amplified when J(i)>0. Large energy gaps are most effectively bridged using
      light collision partners. For efficient vibrational relaxation in polyatomics an
      additional requirement is that the molecular motion of the mode must be capable
      of generating molecular rotation on contact with the collision partner in order
      to meet the angular momentum requirements. We postulate that this may account for
      some of the striking propensities that characterize polyatomic energy transfer.

PMID- 15260536
TI  - High resolution infrared spectra of a carbon dioxide molecule solvated with
      helium atoms.
AB  - Infrared spectra of He(N)-CO(2) clusters with N up to about 20 have been studied
      in the region of the CO(2) nu(3) fundamental band ( approximately 2350 cm(-1))
      using a tunable diode laser spectrometer and pulsed supersonic jet source with
      cooled (>-150 degrees C) pinhole or slit nozzles and high backing pressures (<40
      atm). Compared to previous studies of He(N)-OCS and -N(2)O clusters, the higher
      symmetry of CO(2) results in simpler spectra but less information content.
      Discrete rotation-vibration transitions have been assigned for N=3-17, and their
      analysis yields the variation of the vibrational band origin and B rotational
      constant over this size range. The band origin variation is similar to He(N)-OCS,
      with an initial blueshift up to N=5, followed by a monotonic redshift, consistent
      with a model where the first five He atoms fill a ring around the equator of the
      molecule, forcing subsequent He atom density to locate closer to the ends. The B
      value initially drops as expected for a normal molecule, reaching a minimum for
      N=5. Its subsequent rise for N=6 to 11 can be interpreted as the transition from
      a normal (though floppy) molecule to a quantum solvation regime, where the CO(2)
      molecule starts to rotate separately from the He atoms. For N>13, the B value
      becomes approximately constant with a value about 17% larger than that measured
      in much larger helium nanodroplets.

PMID- 15260537
TI  - Vibrationally inelastic collisions in H+ +CO system: comparing quantum
      calculations with experiments.
AB  - State-resolved cross beam experiments [H. Udseth et al., J. Chem. Phys. 60, 3051
      (1974); J. Krutein and F. Linder, J. Chem. Phys. 71, 599 (1979); G. Niedner
      Schatteburg and J. P. Toennies, Adv. Chem. Phys. LXXXII, 553 (1992)], coupled
      with proton energy loss spectroscopy for the inelastic scattering of H(+) from CO
      in the collision range of 10-30 eV show very low vibrational excitation of the
      target molecule. Stimulated by the experimentally observed low vibrational
      inelasticity in the system the ground and the first two low-lying excited
      electronic potential-energy surfaces have been computed using the ab initio
      multireference configuration interaction method. Quantum dynamics has been
      performed on the ground potential energy surface in the framework of vibrational
      close-coupling rotational infinite-order sudden approximation. The various
      computed dynamical attributes such as differential and integral cross sections,
      and average vibrational energy transfer are analyzed in detail, and compared
      successfully with the available experimental results.

PMID- 15260538
TI  - Aqua dissociation nature of cesium hydroxide.
AB  - To understand the mechanism of aqueous base dissociation chemistry, the ionic
      dissociation of cesium-hydroxide in water clusters is examined using density
      functional theory and ab initio calculations. In this study, we report hydrated
      structures, stabilities, thermodynamic quantities, dissociation energies,
      infrared spectra, and electronic properties of CsOH(H(2)O)(n=0-4). With the
      addition of water molecules, the Cs-OH bond lengthened significantly from 2.46 A
      for n=1 to 3.08 A for n=4, which causes redshift in Cs-O stretching frequency. It
      is found that three water molecules are needed for the dissociation of Cs-OH, in
      contrast to the case of strong acid dissociation which requires at least four
      water molecules. However, the dissociation for n=3 could be considered as
      incomplete because a very weak CS em leader OH stretch mode is still present,
      while that for n=4 is complete since the Cs em leader OH mode no longer exists.
      This study can be related with hydration chemistry of cations and anions, and
      extended into the intra- and intercharge-transfer phenomena.

PMID- 15260539
TI  - Experimental and theoretical study of the structures and binding energies of
      eugenol (H2O)n, n=0-2.
AB  - Eugenol (4-Allyl-2-methoxyphenol), a phenol-derivative with an intramolecular -OH
      ...OCH(3) hydrogen bond (H bond), has been studied in a supersonic expansion
      using a number of complementary laser spectroscopic techniques. The mass-resolved
      excitation spectrum of eugenol and its water complexes are reported for the first
      time. The most intense set of bands on the resonantly enhanced multiphoton
      ionization (REMPI) spectrum of eugenol originate in a conformer whose S(1)<--S(0)
      transition is at 35 202 cm(-1) and the ionization threshold at (I(0)<--S(0)) 62
      544+/-150 cm(-1) (7.755+/-0.019 eV). In addition, two low intensity features
      redshifted with respect to the 0(0) (0) transition have been identified as due to
      a second, less stable conformer. Ab initio calculations show that the potential
      energy landscape depicts at least three minima associated with one folded and two
      extended conformers, one of which is the most stable. Clusters of eugenol/water
      were prepared in a supersonic expansion by seeding eugenol and water in noble gas
      He and examined by two-color REMPI (R2PI) and IR-UV double resonance
      spectroscopies. Only one single isomer was observed for both 1:1 and 1:2
      complexes, in contrast with the several stable conformers provided by the
      computations. The dissociation energies of the 1:1 and 1:2 complexes have been
      determined by the fragmentation threshold method and the results compared with
      those from ab initio calculations conducted at the B3LYP and MP2 levels with a
      variety of basis sets.

PMID- 15260540
TI  - State-selected dynamics of the complex-forming bimolecular reaction Cl- +CH3 Cl'-
      >ClCH3+Cl'-: a four-dimensional quantum scattering study.
AB  - Time-independent quantum scattering calculations have been carried out on the
      Walden inversion S(N)2 reaction Cl(-)+CH(3)Cl(')(v(1),v(2),v(3))-->ClCH(3)(v(1)
      ('),v(2) ('),v(3) ('))+Cl('-). The two C-Cl stretching modes (quantum numbers
      v(3) and v(3) (')) and the totally symmetric internal modes of the methyl group
      (C-H stretching vibration, v(1) and v(1) ('), and inversion bending vibration,
      v(2) and v(2) (')) are treated explicitly. A four-dimensional coupled cluster
      potential energy surface is employed. The scattering problem is formulated in
      hyperspherical coordinates using the exact Hamiltonian and exploiting the full
      symmetry of the problem. Converged state-selected reaction probabilities and
      product distributions have been calculated up to 6100 cm(-1) above the
      vibrational ground state of CH(3)Cl, i.e., up to initial vibrational excitation
      (2,0,0). In order to extract all scattering resonances, the energetic grid was
      chosen to be very fine, partly down to a resolution of 10(-12) cm(-1). Up to 2500
      cm(-1) translational energy, initial excitation of the umbrella bending
      vibration, (0,1,0), is more efficient for reaction than exciting the C-Cl
      stretching mode, (0,0,1). The combined excitation of both vibrations results in a
      synergic effect, i.e., a considerably higher reaction probability than expected
      from the sum of both independent excitations, even higher than (0,0,2) up to 1500
      cm(-1) translational energy. Product distributions show that the umbrella mode is
      strongly coupled to the C-Cl stretching mode and cannot be treated as a spectator
      mode. The reaction probability rises almost linearly with increasing initial
      excitation of the umbrella bending mode. The effect with respect to the C-Cl
      stretch is five times larger for more than two quanta in this mode, and in
      agreement with previous work saturation is found. Exciting the high-frequency C-H
      stretching mode, (1,0,0), yields a large increase for small energies [more than
      two orders of magnitude larger than (0,0,0)], while for translational energies
      higher than 2000 cm(-1), it becomes a pure spectator mode. For combined initial
      excitations including the symmetric C-H stretch, the spectator character of the
      latter is even more pronounced. However, up to more than 1500 cm(-1)
      translational energy, the C-H vibration does not behave adiabatically during the
      course of reaction, because only 20% of the initial energy is found in the same
      mode of the product molecule. The distribution of resonance widths and peak
      heights is discussed, and it is found that individual resonances pertinent to
      intermediate complexes Cl(-)...CH(3)Cl show product distributions independent of
      the initial vibrational state of the reactant molecule. The relatively high
      reactivity, of resonance states with respect to excitation of any mode, found in
      previous work is confirmed in the present calculations. However, reactivity of
      intermediate states and reactivity with respect to initial vibrational excitation
      have to be distinguished. There is a strong mixing between the vibrational states
      reflected in numerous avoided crossings of the hyperspherical adiabatic curves.

PMID- 15260541
TI  - Nuclear quadrupole hyperfine structure in the microwave spectrum of HCl-N2O:
      electric field gradient perturbation of N2O by HCl.
AB  - The microwave spectra of six isotopomers of HCl-N(2)O have been obtained in the 7
      19 GHz region with a pulsed molecular beam, Fourier transform microwave
      spectrometer. The nuclear quadrupole hyperfine structure due to all quadrupolar
      nuclei is resolved and the spectra are analyzed using the Watson S-reduced
      Hamiltonian with the inclusion of nuclear quadrupole coupling interactions. The
      spectroscopic constants determined include rotational constants, quartic and
      sextic centrifugal distortion constants, and nuclear quadrupole coupling
      constants for each quadrupolar nucleus. Due to correlations of the structural
      parameters, the effective structure of the complex cannot be obtained by fitting
      to the spectroscopic constants of the six isotopomers. Instead, the parameters
      for each isotopomer are calculated from the A and C rotational constants and the
      chlorine nuclear quadrupole coupling constant along the a-axis, chi(aa). There
      are two possible structures; the one in which hydrogen of HCl interacts with the
      more electronegative oxygen of N(2)O is taken to represent the complex. The two
      subunits are approximately slipped parallel. For H (35)Cl-(14)N(2)O, the distance
      between the central nitrogen and chlorine is 3.5153 A and the N(2)O and HCl
      subunits form angles of 72.30 degrees and 119.44 degrees with this N-Cl axis,
      respectively. The chlorine and oxygen atoms occupy the opposite, obtuse vertices
      of the quadrilateral formed by O, central N, Cl, and H. Nuclear quadrupole
      coupling constants show that while the electric field gradient of the HCl subunit
      remains essentially unchanged upon complexation, there is electronic
      rearrangement about the two nitrogen nuclei in N(2)O.

PMID- 15260542
TI  - Probes of spin conservation in heavy metal reactions: experimental and
      theoretical studies of the reactions of Re+ with H2, D2, and HD.
AB  - A guided ion beam tandem mass spectrometer is used to examine the kinetic energy
      dependence of reactions of the third-row transition metal cation, Re(+), with
      molecular hydrogen and its isotopologues. A flow tube ion source produces Re(+)
      in its (7)S(3) electronic ground state. Reaction with H(2), D(2), and HD forms Re
      H(+)(Re D(+)) in endothermic processes. Modeling of the endothermic reaction
      cross sections yields the 0 K bond dissociation energy of D(0)(Re(+)-H)=2.29+/
      0.07 eV (221+/-6 kJ/mol). The experimental thermochemistry is consistent with ab
      initio calculations, performed here and in the literature. Theory also provides
      the electronic structures of these species and is used to examine the reactive
      potential energy surfaces. Results from reactions with HD provide insight into
      the reaction mechanisms and indicate that the late metal ion, Re(+), reacts
      largely via a statistical mechanism. This is consistent with the potential energy
      surfaces which locate a stable Re H(2) (+)((5)B(2)) complex. Results for this
      third-row transition metal system are compared with the first-row congener
      (Mn(+)) and found to have much higher reactivity towards dihydrogen and stronger
      M(+)-H bonds. These differences can be attributed to efficient coupling among
      surfaces of different spin along with lanthanide contraction and relativistic
      effects.

PMID- 15260543
TI  - A stimulated emission pumping study of the first excited singlet state of
      germylidene (H2C=Ge).
AB  - The A (1)A(2) states of H(2)CGe and D(2)CGe have been explored for the first time
      by A-X laser-induced fluorescence (LIF) spectroscopy of the orbitally forbidden
      S(1)-S(0) transition and stimulated emission pumping (SEP) and wavelength
      resolved fluorescence studies of the allowed B-A electronic transition. Medium
      resolution SEP studies gave the excited A state nu(2), nu(3), nu(4), and nu(6)
      vibrational frequencies for H(2)C(74)Ge and D(2)C(74)Ge. The 4(1) and 6(1) levels
      and higher combination and overtone states are strongly Coriolis coupled, which
      perturbs the rotational subband structure, limiting the accuracy of the
      determination of the vibrational frequencies. High-resolution SEP studies of the
      B-A 0(0) (0) band have allowed us to determine the rotational constants of the A
      state of H(2)C(74)Ge, from which we were able to calculate an approximate r(0)
      structure with the CH bond length constrained to the ground state value. The zero
      point level of D(2)C(74)Ge is substantially perturbed, most plausibly by
      interaction with an excited vibrational level of the nearby triplet (a (3)A(2))
      state.

PMID- 15260544
TI  - Time-resolved electron detachment imaging of the I- channel in I2Br-
      photodissociation.
AB  - The evolution of the I(-) channel in I(2)Br(-) photodissociation is examined
      using time-resolved negative-ion photoelectron imaging spectroscopy. The 388 nm
      photodetachment images obtained at variable delays following 388 nm excitation
      reveal the transformation of the excess electron from that belonging to an
      excited trihalide anion to that occupying an atomic orbital localized on the I(-)
      fragment. With increasing pump-probe delay, the corresponding photoelectron band
      narrows on a approximately 300 fs time scale. This trend is attributed to the
      localization of the excess-electron wave function on the atomic-anion fragment
      and the establishment of the fragment's electronic identity. The corresponding
      band position drifts towards larger electron kinetic energies on a significantly
      longer, approximately 1 ps, time scale. The gradual spectral shift is attributed
      to exit-channel interactions affecting the photodetachment energetics, as well as
      the photoelectron anisotropy. The time-resolved angular distributions are
      analyzed and found consistent with the formation of the asymptotic I(-) fragment.

PMID- 15260545
TI  - An intrinsic reaction coordinate calculation of the torsion-internal rotation
      potential of hydrogen peroxide and its isotopomers.
AB  - Intrinsic reaction coordinate (IRC) calculations of the internal rotation
      (torsional) potentials for H(2)O(2) and its isotopomers HDO(2) and D(2)O(2) were
      carried out at the CCSD(T)/CBS//aug-cc-pVDZ level. Two extrapolation methods were
      used to obtain energies in the complete basis set (CBS) limit. The full IRC
      potential was constructed from scans from the C(2v) (cis) and C(2h) (trans)
      transition states to the equilibrium C(2) (gauche) structure. The IRC potential
      for H(2)O(2) was fit to a five-term Fourier function; coefficients were compared
      with values obtained from spectroscopic data. The twofold IRC torsional
      potentials were used to obtain torsional eigenvalues, which yielded values of the
      transitions between various ntau states. These results compare favorably with
      Raman and near-infrared data. Our calculations provide values of the cis and
      trans barriers of 2495 and 364 cm(-1), respectively, which are in good agreement
      with both previously calculated and experimentally derived values. It appears
      that coupling between torsional motion and other degrees of freedom is not
      significant in these molecules.

PMID- 15260546
TI  - Extra electron in (H2O)24- cluster isomers: a theoretical study.
AB  - The isomers of (H(2)O)(24) (-) tetrakaidecahedral cluster are studied by applying
      the Becke-3-parameter density functional theory and Lee-Yang-Parr correlation
      functional (B3LYP) and 6-311++G** basis set. Three isomers are selected on the
      basis of stabilization energy values. The vertical electron dissociation energies
      (VDE) of these isomers are 1.353, 0.404, and 0.258 eV, respectively. The
      experimental VDE value of 1.31 eV [J. Chem. Phys. 92, 3980 (1990)] for this
      cluster size is in excellent agreement with that calculated for isomer 1,
      suggesting the dominance of this isomer in the experiment. Four water molecules
      in this isomer share most of the -1 charge. These four water molecules have non-H
      bonding H (NHB H) atoms turned toward the cavity, and the inward turned H atoms
      exhibit a significant lowering of O-H stretch frequency compared to that of a
      monomer. Isomers 2 and 3 have all 12 NHB H atoms projected outward and have the 
      1 charge distributed among 7-8 water molecules on the cluster surface.

PMID- 15260547
TI  - Calculations of long-range potential wells for highly excited homonuclear and
      heteronuclear alkali dimers.
AB  - The weakly bound long-range potential curves between a highly excited alkali atom
      M(*)(n(e)s) and a ground state alkali atom M(n(g)s) are calculated using simple
      but reasonably accurate models for long-range dispersion and exchange
      interactions for all homonuclear and heteronuclear combinations. For K(2), where
      experimental results are available, the agreement is quite good (binding energies
      of observed vibrational levels within approximately 10%). We find that at least a
      zero-point vibrational level occurs for n(e)-n(g)</=12.

PMID- 15260548
TI  - Rydberg-valence interactions of CO, and spectroscopic evidence characterizing the
      C' 1Sigma+ valence state.
AB  - Rotationally cold absorption and two-photon ionization spectra of CO in the 90
      100 nm region have been recorded at a resolution of 0.3-1.0 cm(-1). The analyses
      of up to four isotopomers seek to clarify the observations in regions where the
      Rydberg levels built on the ground state X (2)Sigma(+) of the ion interact with
      valence states of (1)Sigma(+) and (1)Pi symmetry. Previous observations of the
      3ssigma, B (1)Sigma(+) Rydberg state, reviewed by Tchang-Brillet et al. [J. Chem.
      Phys. 96, 6735 (1992)], have been extended to energies above its avoided crossing
      with the repulsive part of the D(') (1)Sigma(+) valence state where resonances of
      varying intensities and widths have been attributed to the fully coupled 3ssigma
      or 4ssigma and D(') potentials, and where the B state approaches a second avoided
      crossing with the C(') (1)Sigma(+) valence state [Cooper and Kirby, J. Chem.
      Phys. 87, 424 (1987); 90, 4895 (1989); Chem. Phys. Lett. 152, 393 (1988)].
      Fragments of a progression of weak and mostly diffuse bands, observed for all
      four isotopomers, have been assigned to the C(')<--X transition. The least
      squares modeling of the 4p and 5p complexes reveals the 3ppi, E (1)Pi Rydberg
      state to be one of the perturbers, violating the Deltav=0 selection rule for
      Rydberg-Rydberg interactions on account of its rapid transition with increasing v
      from Rydberg to valence state. A second (1)Pi perturber, very loosely bound and
      clearly of valence type, contributes to the confusion in the published literature
      surrounding the 5p, v=0 complex.

PMID- 15260549
TI  - Photodetachment spectrum of OHF-: three-dimensional study of the heavy-light
      heavy resonances.
AB  - In this work a simulation of the OHF(-) photodetachment spectrum is performed in
      a three-dimensional potential energy surface recently developed for OHF((3)A(")).
      The ground (2)A(') state potential of the anion is calculated in three dimensions
      based on accurate ab initio calculations and the reaction dynamics is studied
      using a wave packet method. The calculated spectrum shows a sequence of bands
      associated to vibrational HF(v) up to v=3. Each band is formed by a continuous
      spectrum and resonant structures. These resonances are associated to the OH-F
      channel well of the (3)A(") PES, in which fragmentation occurs through
      vibrational predissociation. Above the OH(v=0) threshold a new resonant pattern
      appears corresponding to heavy-light-heavy resonances. Special attention is paid
      to the assignment of these resonances because they mediate the reaction dynamics
      in the OH+F collision at low kinetic energies. The sequence of bands is in rather
      good agreement with that appearing in the experimental spectrum, especially at
      higher electron kinetic energies. At low kinetic energies, however, some other
      electronic states may contribute. The resonance structures might be washed out by
      the rotational average and the relatively low energy resolution of the
      experiment.

PMID- 15260550
TI  - Valence electronic charge density of distorted C60- monomers in polymerized KC60
      and RbC60.
AB  - We investigate the valence electronic charge density of the C(60) (-) monomers in
      (C(60) (-))(n) polymer chains in K- and RbC(60) by means of a nonorthogonal tight
      binding formalism using experimental data on the positions of the carbon atoms.
      Various configurations of the C(60) cages are considered. Starting from the ideal
      icosahedral C(60) structure and moving to the realistic, experimentally
      determined spatial configuration of the C(60) cages in K- and RbC(60), we observe
      a systematic increase of the electric quadrupole moments on the C(60) (-)
      monomers. We also confirm the validity of factorizing the charge density of a
      C(60) (-) monomer into an angular and a radial part.

PMID- 15260551
TI  - A finite-size dynamic-scaling approach for the diffusion front of particles.
AB  - The scaling behavior of the diffusion front, originated by the random motion of
      particles under a concentration gradient, is studied by means of the Monte Carlo
      method and solving the diffusion equation. Simulations are performed on the
      square lattice using confined geometries of size MxL, where the gradient is
      established along the M direction while periodic boundary conditions are set
      along the L direction. A dynamic scaling Ansatz is proposed such as the width of
      the front [w(M,t)] scales as w(M,t) approximately M(alpha)f(t/M(alpha/beta)),
      where alpha and beta are the roughness and growing exponents, respectively. This
      proposal is based on the fact that the development of w is constrained by the
      gradient, that decays as M(-1), in contrast to the standard Family-Vicsek scaling
      Ansatz where correlations are constrained by the lateral dimension of the sample.
      It is found that the roughness exponent exhibits a systematic dependence on the
      sample size that can be rationalized in terms of a finite-size correction.
      Extrapolation to the thermodynamic limit gives alpha=4/7, in excellent agreement
      with theoretical predictions linking the diffusion system to the percolation
      problem. The evaluation of the growing exponent gives beta=0.30+/-0.02, leading
      us to the conjecture beta=2/7 for the exact value.

PMID- 15260552
TI  - A theory of electrical conductivity of molten salt. II.
AB  - In molten equivalent salts, a unified relation that the ratio of partial dc
      conductivities is always equal to the inverse mass ratio, viz. sigma(+)/sigma(
      )=m(-)/m(+), has been confirmed in view of microscopic point starting from the
      generalized Langevin equation. It has been newly proved that the memory functions
      assumed to be an exponentially decaying form in the Langevin equation for cation
      and anion are equal to each other. Furthermore, the short time behaviors of
      moving ions are analyzed in terms of their velocity correlation functions,
      according to the combination of generalized Langevin equation and damped Einstein
      oscillator equation. A minor correction for the expression of common friction
      constant derived before has been given. Estimated results for conductivities are
      close to those obtained by computer simulation and also comparable to
      experimental values.

PMID- 15260553
TI  - Spectroscopy of K+ x Rg and transport coefficients of K+ in Rg (Rg=He-Rn).
AB  - Ab initio calculations employing the coupled-cluster method, with single and
      double substitutions and accounting for triple excitations noniteratively
      [CCSD(T)], are used to obtain accurate potential energy curves for the K(+)He,
      K(+)Ne, K(+)Ar, K(+)Kr, K(+)Xe, and K(+)Rn cationic complexes. From these
      potentials, rovibrational energy levels and spectroscopic parameters are
      calculated. In addition, mobilities and diffusion coefficients for K(+) cations
      moving through the six rare gases are calculated, under conditions that match
      previous experimental determinations. A detailed statistical comparison of the
      present and previous potentials is made with available experimental data, and
      critical conclusions are drawn as to the reliability of each set of data. It is
      concluded that the present ab initio potentials match the accuracy of the best
      model potentials and the most reliable experimental data.

PMID- 15260554
TI  - Effect of internal gradients in the nuclear magnetic resonance measurement of the
      surface-to-volume ratio.
AB  - We consider a system of spins diffusing in a static inhomogeneous (nonuniform
      gradient) magnetic field B in a restricted geometry and in the presence of
      surface relaxation. We show that the short-time diffusional decay of nuclear
      magnetization is controlled by the field scattering kernel F(t) identical with
      [B(t)-B(0)](2), which is a measure of the average field inhomogeneity sampled by
      the spins in time t and does not depend on the particular sequence of radio
      frequency pulses used. Magnetization in arbitrary sequences can be
      straightforwardly computed by evaluating elementary integrals of F(t). Diffusion
      takes place while the field is on, so that the spins precess as they diffuse, in
      contrast to the simpler problem of purely classical diffusion considered in [P.
      P. Mitra, P. N. Sen, and L. M. Schwartz, Phys. Rev. B 47, 8565 (1993)] which is
      applicable only to the ideal pulsed-field gradient experiment. We compute the
      short-time asymptotic form of F(t) and find that it depends on the surface-to
      volume ratio (S/V) of the pore space as well as on the average of the gradients
      over the bounding surface. In a system with nonuniform gradients that vary faster
      near the surface than in the bulk, as for internal susceptibility fields, this
      gradient surface average may be much larger than the gradients in the bulk,
      significantly enhancing the apparent S/V. We discuss the application of our
      results to the widely used Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence as
      well as proposing a modification of it, which we term "padded" CPMG, that may be
      preferable in systems with significant surface relaxation. We indicate how each
      sequence can be used to probe the internal fields.

PMID- 15260555
TI  - Vibrational coherence transfer characterized with Fourier-transform 2D IR
      spectroscopy.
AB  - Two-dimensional infrared (2D IR) spectroscopy of the symmetric and asymmetric
      C[Triple Bond]O stretching vibrations of Rh(CO)(2)acac in hexane has been used to
      investigate vibrational coherence transfer, dephasing, and population relaxation
      in a multilevel vibrational system. The transfer of coherence between close-lying
      vibrational frequencies results in extra relaxation-induced peaks in the 2D IR
      spectrum, whose amplitude depends on the coherence transfer rate. Coherence
      transfer arises from the mutual interaction of the bright CO stretches with dark
      states, which in this case reflects the mutual d-pi(*) back bonding of the Rh
      center to both the terminal carbonyls and the acetylacenonate ligand. For 2D IR
      relaxation experiments with variable waiting times, coherent dynamics lead to the
      modulation of peak amplitudes, while incoherent population relaxation and
      exchange results in the growth of the relaxation-induced peaks. We have modeled
      the data by propagating the density matrix with the Redfield equation,
      incorporating all vibrational relaxation processes during all three experimental
      time periods and including excitation reorientation effects arising from
      relaxation. Coherence and population transfer time scales from the symmetric to
      the asymmetric stretch were found to be 350 fs and 3 ps, respectively. We also
      discuss a diagrammatic approach to incorporating all vibrational relaxation
      processes into the nonlinear response function, and show how coherence transfer
      influences the analysis of structural variables from 2D IR spectroscopy.

PMID- 15260556
TI  - Elucidating the initial dynamics of electron photodetachment from atoms in
      liquids using variably-time-delayed resonant multiphoton ionization.
AB  - We study the photodetachment of electrons from sodium anions in room temperature
      liquid tetrahydrofuran (THF) using a new type of three-pulse pump-probe
      spectroscopy. Our experiments use two variably-time-delayed pulses for excitation
      in what is essentially a resonant 1+1 two-photon ionization: By varying the
      arrival time of the second excitation pulse, we can directly observe how solvent
      motions stabilize and trap the excited electron prior to electron detachment.
      Moreover, by varying the arrival times of the ionization (excitation) and probe
      pulses, we also can determine the fate of the photoionized electrons and the
      distance they are ejected from their parent Na atoms. We find that as solvent
      reorganization proceeds, the second excitation pulse becomes less effective at
      achieving photoionization, and that the solvent motions that stabilize the
      excited electron following the first excitation pulse occur over a time of
      approximately 450 fs. We also find that there is no spectroscopic evidence for
      significant solvent relaxation after detachment of the electron is complete. In
      combination with the results of previous experiments and molecular dynamics
      simulations, the data provide new insight into the role of the solvent in
      solution-phase electron detachment and charge-transfer-to-solvent reactions.

PMID- 15260557
TI  - Relaxation dynamics of a linear molecule in a random static medium: a scaling
      analysis.
AB  - We present extensive molecular dynamics simulations of the motion of a single
      linear rigid molecule in a two-dimensional random array of fixed overlapping
      disklike obstacles. The diffusion constants for the center of mass translation,
      D(CM), and for rotation, D(R), are calculated for a wide range of the molecular
      length, L, and the density of obstacles, rho. The obtained results follow a
      master curve Drho(micro) approximately (L(2)rho)(-nu) with an exponent micro=-3/4
      and 1/4 for D(R) and D(CM), respectively, that can be deduced from simple scaling
      and kinematic arguments. The nontrivial positive exponent nu shows an abrupt
      crossover at L(2)rho=zeta(1). For D(CM) we find a second crossover at
      L(2)rho=zeta(2). The values of zeta(1) and zeta(2) correspond to the average
      minor and major axis of the elliptic holes that characterize the random
      configuration of the obstacles. A violation of the Stokes-Einstein-Debye relation
      is observed for L(2)rho>zeta(1), in analogy with the phenomenon of enhanced
      translational diffusion observed in supercooled liquids close to the glass
      transition temperature.

PMID- 15260558
TI  - Study of nonsteady diffusional growth of a droplet in a supersaturated vapor:
      treatment of the moving boundary and material balance.
AB  - A new mathematical treatment of the problem of droplet growth via diffusion of
      molecules from a supersaturated vapor is presented. The theory is based on a
      semiquantitative analysis with good physical arguments and is justified by its
      reasonable predictions. For example it recovers the time honored growth law in
      which, to a high degree of approximation, the droplet radius increases with the
      square root of time. Also, to a high degree of approximation, it preserves
      material balance such that, at any time, the number of molecules lost from the
      vapor equals the number in the droplet. Estimates of the remaining
      approximational error are provided. On another issue, we show that, in contrast,
      the conventional treatment of droplet growth does not maintain material balance.
      This issue could be especially important for the nucleation of another droplet in
      the vicinity of the growing droplet where the rate of nucleation depends
      exponentially on supersaturation. Suggestions for further improvement of rigor
      are discussed.

PMID- 15260559
TI  - Conductivity of solvated electrons in hexane investigated with terahertz time
      domain spectroscopy.
AB  - We present investigations of the transient photoconductivity and recombination
      dynamics of quasifree electrons in liquid n-hexane and cyclohexane performed
      using terahertz time-domain spectroscopy (THz-TDS). Quasifree electrons are
      generated by two-photon photoionization of the liquid using a femtosecond
      ultraviolet pulse, and the resulting changes in the complex conductivity are
      probed by a THz electromagnetic pulse at a variable delay. The detection of time
      domain wave forms of the THz electric field permits the direct determination of
      both the real and the imaginary part of the conductivity of the electrons over a
      wide frequency range. The change in conductivity can be described by the Drude
      model, thus yielding the quasifree electron density and scattering time. The
      electron density is found to decay on a time scale of a few hundred picoseconds,
      which becomes shorter with increasing excitation density. The dynamics can be
      described by a model that assumes nongeminate recombination between electrons and
      positive ions. In addition, a strong dependence of the quasifree electron density
      on temperature is observed, in agreement with a two-state model in which the
      electron may exist in either a quasifree or a bound state.

PMID- 15260560
TI  - NMR measurement of self-diffusion coefficients by slice selection.
AB  - Most of the time, so-called inversion-recovery experiments concern longitudinal
      nuclear magnetization of the whole sample, the region of interest being limited
      by the transmitting-receiving coil. Here we address the question of what occurs
      if the region of interest is purposely limited to a thin slice selected by means
      of procedures employing magnetic field gradients. Gradients of both magnetic
      fields (B(0), the static magnetic field, and B(1), the radio-frequency magnetic
      field) can be used. In this study we resorted essentially to B(1) gradients and
      novel procedures, based on the natural inhomogeneity of the B(1) field delivered
      by a saddle coil, are described. It is obvious that molecules leaving and
      entering the slice during the evolution (recovery) period should influence the
      magnetization recovery. Molecular self-diffusion is responsible for such effects,
      experimentally visible and accounted for by an appropriate theory which has been
      approximated for by permitting an easy physical assessment. This approach should
      lead to alternative methods for measuring self-diffusion coefficients.

PMID- 15260561
TI  - Theory of covariance nuclear magnetic resonance spectroscopy.
AB  - Covariance nuclear magnetic resonance (NMR) spectroscopy provides an effective
      way for establishing nuclear spin connectivities in molecular systems. The
      method, which identifies correlated spin dynamics in terms of covariances between
      1D spectra, benefits from a high spectral resolution along the indirect dimension
      without requiring apodization and Fourier transformation along this dimension.
      The theoretical treatment of covariance NMR spectroscopy is given for NOESY and
      TOCSY experiments. It is shown that for a large class of 2D NMR experiments the
      covariance spectrum and the 2D Fourier transform spectrum can be related to each
      other by means of Parseval's theorem. A general procedure is presented for the
      construction of a symmetric spectrum with improved resolution along the indirect
      frequency domain as compared to the 2D FT spectrum.

PMID- 15260562
TI  - Using path sampling to build better Markovian state models: predicting the
      folding rate and mechanism of a tryptophan zipper beta hairpin.
AB  - We propose an efficient method for the prediction of protein folding rate
      constants and mechanisms. We use molecular dynamics simulation data to build
      Markovian state models (MSMs), discrete representations of the pathways sampled.
      Using these MSMs, we can quickly calculate the folding probability (P(fold)) and
      mean first passage time of all the sampled points. In addition, we provide
      techniques for evaluating these values under perturbed conditions without
      expensive recomputations. To demonstrate this method on a challenging system, we
      apply these techniques to a two-dimensional model energy landscape and the
      folding of a tryptophan zipper beta hairpin.

PMID- 15260563
TI  - Lattice density functional theory of molecular diffusion.
AB  - A density functional theory of diffusion is developed for lattice fluids with
      molecular flux as a functional of the density distribution. The formalism
      coincides exactly with the generalized Ono-Kondo density functional theory when
      there is no gradient of chemical potential, i.e., at equilibrium. Away from
      equilibrium, it gives Fick's first law in the absence of a potential energy
      gradient, and it departs from Fickian behavior consistently with the Maxwell
      Stefan formulation. The theory is applied to model a nanopore, predicting
      nonequilibrium phase transitions and the role of surface diffusion in the
      transport of capillary condensate.

PMID- 15260564
TI  - Ultrafast photoinduced reflectivity transients in doped manganite.
AB  - The temperature and magnetic field dependence of ultrafast photoinduced spin and
      quasiparticle relaxation dynamics is reported in La(0.67)Ca(0.33)MnO(3) and
      LaMnO(3) single crystals and thin films. Both manganites reveal an unusually slow
      ( approximately 10 micros) carrier relaxation process attributed to the spin
      lattice relaxation in localized states. The quasiparticle dynamics is governed by
      the temperature- and magnetic field-dependent pseudogap in
      La(0.67)Ca(0.33)MnO(3), and by the temperature-independent Jahn-Teller gap in
      LaMnO(3). The loss of spectral weight near the Fermi level in
      La(0.67)Ca(0.33)MnO(3) strongy affects the quasiparticle relaxation dynamics as
      temperature increases from below T(C). Our results show that the coupled dynamics
      of charge, spin and lattice is strongly correlated with the distinct gap
      structures in these manganites.

PMID- 15260565
TI  - GeO2 fibers: preparation, morphology and photoluminescence property.
AB  - Nanomicron to submicron fibers of GeO(2) have been prepared using poly(vinyl
      acetate) and germanium dioxide sol by electrospinning followed by high
      temperature calcination. The morphology of the fibers have been studied by
      scanning electron microscopy, transmission electron microscopy, and atomic force
      microscopy. X-ray diffraction indicates that the fibers are single crystal with
      hexagonal alpha-phase quartz-like structure. At room temperature, the fibers show
      photoluminescence under excitation at 325 nm. The fibers may have potential
      applications in one-dimensional optoelectronic nanodevices.

PMID- 15260566
TI  - Thermal physics in carbon nanotube growth kinetics.
AB  - The growth of single wall carbon nanotubes (SWNTs) mediated by metal
      nanoparticles is considered within (i) the surface diffusion growth kinetics
      model coupled with (ii) a thermal model taking into account heat release of
      carbon adsorption-desorption on nanotube surface and carbon incorporation into
      the nanotube wall and (iii) carbon nanotube-inert gas collisional heat exchange.
      Numerical simulations performed together with analytical estimates reveal various
      temperature regimes occurring during SWNT growth. During the initial stage, which
      is characterized by SWNT lengths that are shorter than the surface diffusion
      length of carbon atoms adsorbed on the SWNT wall, the SWNT temperature remains
      constant and is significantly higher than that of the ambient gas. After this
      stage the SWNT temperature decreases towards that of gas and becomes nonuniformly
      distributed over the length of the SWNT. The rate of SWNT cooling depends on the
      SWNT-gas collisional energy transfer that, from molecular dynamics simulations,
      is seen to be efficient only in the SWNT radial direction. The decreasing SWNT
      temperature may lead to solidification of the catalytic metal nanoparticle
      terminating SWNT growth or triggering nucleation of a new carbon layer and growth
      of multiwall carbon nanotubes.

PMID- 15260567
TI  - Brownian dynamics simulations of simplified cytochrome c molecules in the
      presence of a charged surface.
AB  - Simulations were performed for up to 150 simplified spherical horse heart
      cytochrome c molecules in the presence of a charged surface, which serves as an
      approximate model for a lipid membrane. Screened electrostatic and short-ranged
      attractive as well as repulsive van der Waals forces for interparticle and
      particle-membrane interactions are utilized in the simulations. At a distance
      from the membrane, where particle-membrane interactions are negligible, the
      simulation is coupled to a noninteraction continuum analogous to a heat bath
      [Geyer et al., J. Chem. Phys. 120, 4573 (2004)]. From the particles' density
      profiles perpendicular to the planar surface binding isotherms are derived and
      compared to experimental results [Heimburg et al. (1999)]. Using a negatively
      charged structureless membrane surface a saturation effect was found for
      relatively large particle concentrations. Since biological membranes often
      contain membrane proteins, we also studied the influence of additional charges on
      our model membrane mimicking bacterial reaction centers. We find that the onset
      of the saturation occurs for much lower concentrations and is sensitive to the
      detailed implementation. Therefore we suggest that local distortion of membrane
      planarity (undulation), or lipid demixing, or the presence of charged integral
      membrane proteins create preferential binding sites on the membrane. Only then do
      we observe saturation at physiological concentrations.

PMID- 15260568
TI  - The interaction of oxygen with TiC(001): photoemission and first-principles
      studies.
AB  - High-resolution photoemission and first-principles density-functional slab
      calculations were used to study the interaction of oxygen with a TiC(001)
      surface. Atomic oxygen is present on the TiC(001) substrate after small doses of
      O(2) at room temperature. A big positive shift (1.5-1.8 eV) was detected for the
      C 1s core level. These photoemission studies suggest the existence of strong O<-
      >C interactions. A phenomenon corroborated by the results of first-principles
      calculations, which show a CTiTi hollow as the most stable site for the
      adsorption of O. Ti and C atoms are involved in the adsorption and dissociation
      of the O(2) molecule. In general, the bond between O and the TiC(001) surface
      contains a large degree of ionic character. The carbide-->O charge transfer is
      substantial even at high coverages (>0.5 ML) of oxygen. At 500 K and large doses
      of O(2), oxidation of the carbide surface occurs with the removal of C and
      formation of titanium oxides. There is an activation barrier for the exchange of
      Ti-C and Ti-O bonds which is overcome only by the formation of C-C or C-O bonds
      on the surface. The mechanism for the removal of a C atom as CO gas involves a
      minimum of two O adatoms, and three O adatoms are required for the formation of
      CO(2) gas. Due to the high stability of TiC, an O adatom alone cannot induce the
      generation of a C vacancy in a flat TiC(001) surface.

PMID- 15260569
TI  - On the encapsulation of nickel clusters by molecular nitrogen.
AB  - The structures and energetic effects of molecular nitrogen adsorbates on nickel
      clusters are investigated using an extended Huckel model coupled with two models
      of the adsorbate-nickel interaction. The potential parameters for the adsorbates
      are chosen to mimic experimental information about the binding strength of
      nitrogen on both cluster and bulk surface phases of nickel. The first model
      potential is a simple Lennard-Jones interaction that leads to binding sites in
      holes defined by sets of near-neighbor nickel atoms. The second model potential
      has a simple three-body form that forces the model nitrogen adsorbates to bind
      directly to single nickel atoms. Significant rearrangement of the core nickel
      structures are found in both models. A disconnectivity graph analysis of the
      potential energy surfaces implies that the rearrangements arise from low
      transition state barriers and the small differences between available isomers in
      the nickel core.

PMID- 15260570
TI  - Spherical particle in Poiseuille flow between planar walls.
AB  - We study a spherical mesoparticle suspended in Newtonian fluid between plane
      parallel walls with incident Poiseuille flow. Using a two-dimensional Fourier
      transform technique we obtain a symmetric analytic expression for the Green
      tensor for the Stokes equations describing the creeping flow in this geometry.
      From the matrix elements of the Green tensor with respect to a complete vector
      harmonic basis, we obtain the friction matrix for the sphere. The calculation of
      matrix elements of the Green tensor is done in large part analytically, reducing
      the evaluation of these elements to a one-dimensional numerical integration. The
      grand resistance and mobility matrices in Cartesian form are given in terms of 13
      scalar friction and mobility functions which are expressed in terms of certain
      matrix elements calculated in the spherical basis. Numerical calculation of these
      functions is shown to converge well and to agree with earlier numerical
      calculations based on boundary collocation. For a channel width broad with
      respect to the particle radius, we show that an approximation defined by a
      superposition of single-wall functions is reasonably accurate, but that it has
      large errors for a narrow channel. In the two-wall geometry the friction and
      mobility functions describing translation-rotation coupling change sign as a
      function of position between the two walls. By Stokesian dynamics calculations
      for a polar particle subject to a torque arising from an external field, we show
      that the translation-rotation coupling induces sideways migration at right angles
      to the direction of fluid flow.

PMID- 15260571
TI  - The effect of atomic substitution on electron-phonon interactions in negatively
      charged B, N-substituted acenes.
AB  - Electron-phonon interactions in the monoanions of B, N-substituted acenes such as
      B(3)N(3)F(6) (1f) and B(5)N(5)F(8) (2f) are studied, and compared with those in
      the monoanions of B(3)N(3)H(6) (1h) and B(5)N(5)H(8) (2h), and B(3)N(3)D(6) (1d)
      and B(5)N(5)D(8) (2d). The low frequency modes around 500 cm(-1) as well as the
      frequency modes higher than 1000 cm(-1) strongly couple to the lowest unoccupied
      molecular orbitals (LUMO) in 1f and 2f. The total electron-phonon coupling
      constants (l(LUMO)) are estimated to be 2.710 and 2.054 eV for 1f and 2f,
      respectively, and those are estimated to be 0.342 and 0.235 eV for 1d and 2d,
      respectively, while those were estimated to be 0.340 and 0.237 eV for 1h and 2h,
      respectively. That is, the l(LUMO) value increases much more significantly by H-F
      substitution than by H-D substitution in B, N-substituted acenes. The larger
      displacements of B and N atoms in the vibronic active modes in 1f and 2f than
      those in 1d and 2d due to larger atomic mass of fluorine than that of deuterium,
      and the phase patterns difference between the LUMO in 1f and 2f, in which the
      atomic orbitals between N and its neighboring F atoms form strong sigma
      antibonding interactions, and that in 1d and 2d, in which the atomic orbitals
      between two neighboring B and N atoms form weak pi-bonding and pi-antibonding
      interactions, are the main reason why the l(LUMO) value increases much more
      significantly by H-F substitution than by H-D substitution. The reorganization
      energies between the neutral molecules and the corresponding monoanions are
      estimated to be 0.122, 0.063, 0.733, and 0.830 eV for 1h, 2h, 1f, and 2f,
      respectively. Therefore, the estimated reorganization energies between the
      neutral molecules and the corresponding monoanions for 1f and 2f are much larger
      than those for 1h and 2h.

PMID- 15260572
TI  - Embedding and self-organization of nanoparticles in phospholipid multilayers.
AB  - Multilayers of various phospholipids on silicon substrates are used to induce
      spontaneous embedding of nanoparticles deposited from the gas phase. The
      resulting nanoparticle arrangement on the substrate surface is characterized
      using atomic force and scanning electron microscopy. In the intermediate phase
      and the liquid crystalline phase of the lipid, a monolayer is formed around
      individual nanoparticles which leads to an increase in interparticle distances.
      At the same time, the molecular mobility of the multilayers allows for self
      assembly of the particles in regular two-dimensional arrangements.

PMID- 15260573
TI  - Manifestation of grain boundaries in the transport properties of p-sexiphenyl
      films.
AB  - Direct current conductivity of p-sexiphenyl films with 0.2-2.5 microm thickness
      deposited on glass substrates was investigated at temperatures between 10 and 300
      K. The molecular dynamics simulations and quantum chemical calculations of the
      experimentally observed conductivity have shown that there exist at least three
      different states of the films effectively contributing to the observed features
      of the dc conductivity: conductivity caused by proper crystalline states,
      conductivity originated from amorphous-like inter-grain region and caused by
      grain's boundary. Comparison of the experimental data and theoretically
      calculated dependences shows that the main contribution to the observed dc
      conductivity gives grain boundaries between polycrystalline grains and amorphous
      like background, though the latter possesses a relatively low part of the total
      volume.

PMID- 15260574
TI  - Epitaxial growth of pentacene films on Cu110.
AB  - The molecular structure of thin pentacene (C(22)H(14)) films grown on a Cu(110)
      surface has been studied by means of He atom scattering, low energy electron
      diffraction, thermal desorption spectroscopy, x-ray photoelectron spectroscopy,
      and x-ray absorption spectroscopy. Depending on the actual film thickness three
      different crystalline phases have been identified which reveal a characteristic
      reorientation of the molecular plane relative to the substrate surface. In the
      monolayer regime the molecules form a highly ordered commensurate (6.5x2)
      structure with a planar adsorption geometry. For thin multilayers (thickness <2
      nm) a second phase is observed which is characterized by a lateral ((-0.65 5.69)
      ( 1.90 1.37)) structure and a tilting of the molecular plane of about 28 degrees
      around their long axis which remains parallel to the surface. Finally, when
      exceeding a thickness of about 2 nm subsequent growth proceeds with an upright
      molecular orientation and leads to the formation of crystalline films which are
      epitaxially oriented with respect to the substrate. The present study thus
      demonstrates that also on metal substrates highly ordered pentacene films with an
      upright orientation of the molecular planes can be grown. Photoelectron
      spectroscopy data indicate further that thick films do not grow in a layer-by
      layer mode but reveal a significant degree of roughness.

PMID- 15260575
TI  - Phase diagram of the adhesive hard sphere fluid.
AB  - The phase behavior of the Baxter adhesive hard sphere fluid has been determined
      using specialized Monte Carlo simulations. We give a detailed account of the
      techniques used and present data for the fluid-fluid coexistence curve as well as
      parametrized fits for the supercritical equation of state and the percolation
      threshold. These properties are compared with the existing results of Percus
      Yevick theory for this system.

PMID- 15260576
TI  - Modeling diffusion in miscible polymer blend films.
AB  - Recent experiments designed to probe polymer transport in the bulk and in the
      vicinity of surfaces have examined the interdiffusion of multilayer sandwiches of
      isotopically labeled polymers. The measured time dependent concentration profiles
      normal to the surface are typically fit to Fick's law, with a single fitting
      parameter, the mutual binary diffusion coefficient (MBDC). The resulting MBDCs
      are found to vary over a broad range of film thicknesses and time, with the time
      dependence being viewed as a unique signature of the reptation mechanism of long
      chain motion, and the thickness dependence being attributed to the slowing down
      of chain dynamics near surfaces. Since the experiments are conducted at finite
      concentration, the MBDC, which is a product of the bare mobility and the
      concentration derivative of the chemical potential, could be dominated by the
      time and thickness dependence of this second term (which is ignored in Fick's
      law). To quantify this conjecture we consider the more rigorous Cahn formulation
      of the diffusion problem in terms of chemical potential gradients. We use square
      gradient theory to evaluate chemical potentials, and fit the resulting time
      dependent concentration profiles to the analytical solution of Fick's law. By
      thus mimicking the experimental analysis we find that the apparent MBDCs vary
      with time as t(-1/2) at short times, in good agreement with existing experiments.
      We show that this time dependence reflects the system's desire to minimize
      concentration gradients, a fact ignored in Fick's law. Since these arguments make
      no reference to the mechanism of chain motion, we argue that the time dependence
      of MBDC derived from interdiffusion experiments does not provide unequivocal
      support for the reptation mechanism of long chain transport. The MBDC values,
      which also vary with the degree of confinement, are predicted to increase with
      decreasing thickness for model parameters corresponding to experimental systems.
      In contrast, since the experimental fits yield an opposite trend, we suggest that
      the bare mobility of the chains decreases strongly with decreasing thickness.
      These findings strongly support the idea that the chains are "pinned"
      irreversibly to the surfaces, in good agreement with other, independent
      experiments.

PMID- 15260577
TI  - Proton field-cycling nuclear magnetic resonance relaxometry in the smectic A
      mesophase of thermotropic cyanobiphenyls: Effects of sonication.
AB  - Proton field-cycling nuclear magnetic resonance relaxometry is used to study the
      spin-lattice relaxation dispersion of selected standard smectic A liquid crystals
      at different temperatures. Relaxation features at both, in the presence and
      absence of a monochromatic ultrasonic field are considered. We show that the
      laboratory-frame spin-lattice relaxation time is mainly governed by translational
      diffusion. Order director fluctuations (ODF) are less important while rotational
      diffusion seems to be only relevant near the clearing point. Our study suggests
      that sonication enhances the ODF contribution in the SmA mesophase. Within the
      framework of the approach we have outlined, different features associated with
      the ODF mechanism can be investigated.

PMID- 15260578
TI  - Theoretical analysis and computer simulation of fluorescence lifetime
      measurements. I. Kinetic regimes and experimental time scales.
AB  - The configuration-controlled regime and the diffusion-controlled regime of
      conformation-modulated fluorescence emission are systematically studied for
      Markovian and non-Markovian dynamics of the reaction coordinate. A path integral
      simulation is used to model fluorescence quenching processes on a semiflexible
      chain. First-order inhomogeneous cumulant expansion in the configuration
      controlled regime defines a lower bound for the survival probability, while the
      Wilemski-Fixman approximation in the diffusion-controlled regime defines an upper
      bound. Inclusion of the experimental time window of the fluorescence measurement
      adds another dimension to the two kinetic regimes and provides a unified
      perspective for theoretical analysis and experimental investigation. We derive a
      rigorous generalization of the Wilemski-Fixman approximation [G. Wilemski and M.
      Fixman, J. Chem. Phys. 60, 866 (1974)] and recover the 1/D expansion of the
      average lifetime derived by Weiss [G. H. Weiss, J. Chem. Phys. 80, 2880 (1984)].

PMID- 15260579
TI  - Theoretical analysis and computer simulation of fluorescence lifetime
      measurements. II. Contour length dependence of single polymers.
AB  - Fluorescence lifetime measurements in a polymer chain are modeled using a memory
      function expansion, computer simulations, and simple scaling arguments. Unless
      the quenching rate is localized and infinitely fast, the fluorescence lifetime is
      generally not equivalent to the first passage time. The fluorescence lifetime
      distribution is decomposed into memory functions that can be measured separately
      in single-molecule experiments. The leading order of the expansion gives the
      Wilemski-Fixman (WF) approximation, and the convergence of higher order terms
      determines its validity. Simulations of the fluorescence quenching on a Rouse
      chain verify the accuracy of the WF approximation at small contact radii, short
      contour lengths, and small quenching rates. Detailed investigation of the average
      fluorescence lifetime reveals two competing mechanisms: the independent motion of
      end-to-end vector, which dominates at small contact radius, and the slowest
      relaxation of polymer, which dominates at large contact radius. The Wilemski
      Fixman rate is used in combination with scaling arguments to predict the
      dependence of fluorescence lifetime on the contour length. Our predictions for
      the scaling of the average lifetime with the contour length are in good agreement
      with both simulations and recent experiments by Eaton and his group [L. J.
      Lapidus, W. A. Eaton, and J. Hofrichter, Proc. Natl. Acad. Sci. U.S.A. 97, 7220
      (2000)].

PMID- 15260580
TI  - Interplay between shear flow and elastic deformations in liquid crystals.
AB  - We study shear flow in liquid crystal cells with elastic deformations using a
      lattice Boltzmann scheme that solves the full, three-dimensional Beris-Edwards
      equations of hydrodynamics. We consider first twisted and hybrid aligned nematic
      cells, in which the deformation is imposed by conflicting anchoring at the
      boundaries. We find that backflow renders the velocity profile non Newtonian, and
      that the director profile divides into two regions characterized by different
      director orientations. We next consider a cholesteric liquid crystal, in which a
      twist deformation is naturally present. We confirm the presence of secondary flow
      for small shear rates, and are able to follow the dynamical pathway of shear
      induced unwinding, for higher shear rates. Finally, we analyze how the coupling
      between shear and elastic deformation can affect shear banding in an initially
      isotropic phase. We find that for a nematic liquid crystal, elastic distortions
      may cause an asymmetry in the dynamics of band formation, whereas for a
      cholesteric, shear can induce twist in an initially isotropic sample.

PMID- 15260581
TI  - Importance of chirality and reduced flexibility of protein side chains: a study
      with square and tetrahedral lattice models.
AB  - Side chains of amino acid residues are the determining factor that distinguishes
      proteins from other unstable chain polymers. In simple models they are often
      represented implicitly (e.g., by spin states) or simplified as one atom. Here we
      study side chain effects using two-dimensional square lattice and three
      dimensional tetrahedral lattice models, with explicitly constructed side chains
      formed by two atoms of different chirality and flexibility. We distinguish
      effects due to chirality and effects due to side chain flexibilities, since
      residues in proteins are L residues, and their side chains adopt different
      rotameric states. For short chains, we enumerate exhaustively all possible
      conformations. For long chains, we sample effectively rare events such as compact
      conformations and obtain complete pictures of ensemble properties of
      conformations of these models at all compactness region. This is made possible by
      using sequential Monte Carlo techniques based on chain growth method. Our results
      show that both chirality and reduced side chain flexibility lower the folding
      entropy significantly for globally compact conformations, suggesting that they
      are important properties of residues to ensure fast folding and stable native
      structure. This corresponds well with our finding that natural amino acid
      residues have reduced effective flexibility, as evidenced by statistical analysis
      of rotamer libraries and side chain rotatable bonds. We further develop a method
      calculating the exact side chain entropy for a given backbone structure. We show
      that simple rotamer counting underestimates side chain entropy significantly for
      both extended and near maximally compact conformations. We find that side chain
      entropy does not always correlate well with main chain packing. With explicit
      side chains, extended backbones do not have the largest side chain entropy. Among
      compact backbones with maximum side chain entropy, helical structures emerge as
      the dominating configurations. Our results suggest that side chain entropy may be
      an important factor contributing to the formation of alpha helices for compact
      conformations.

PMID- 15260582
TI  - Phase transitions of a polymer threading a membrane coupled to coil-globule
      transitions.
AB  - We theoretically study phase transitions of a polymer threading through a pore
      imbedded in a membrane. We focus on the coupling between a partition of the
      polymer segments through the membrane and a coil-globule transition of the single
      polymer chain. Based on the Flory model for collapse transitions of a polymer
      chain, we calculate the fraction of polymer segments and the expansion factor of
      a polymer coil on each side of the membrane. We predict a first-order phase
      transition of a polymer threading a membrane; polymer segments in one side are
      discontinuously translocated into the other side, depending on solvent conditions
      and molecular weight of the polymer. We also discuss the equilibrium conformation
      of the polymer chain on each side of the membrane.

PMID- 15260583
TI  - Time-dependent density-functional calculations of S0-S1 transition energies of
      poly(p-phenylene vinylene).
AB  - We used time-dependent density-functional-theory (TDDFT) approaches to calculate
      absorption (S(0)-->S(1)) and emission (S(1)-->S(0)) transition energies of poly(p
      phenylene vinylene) (PPV). The absorption and emission energies were estimated to
      be 2.44 and 2.16 eV, respectively, from the extrapolation of calculated results
      for oligomers. Comparisons with available experimental data demonstrated that
      TDDFT is a very reliable tool for investigating the electronic transitions of
      PPV.

PMID- 15260584
TI  - Influence of solvent quality on polymer solutions: a Monte Carlo study of bulk
      and interfacial properties.
AB  - The effect of solvent quality on dilute and semidilute regimes of polymers in
      solution is studied by means of Monte Carlo simulations. The equation of state,
      adsorption near a hard wall, wall-polymer surface tension, and effective
      depletion potential are all calculated as a function of concentration and solvent
      quality. We find important differences between polymers in good and theta
      solvents. In the dilute regime, the physical properties for polymers in a theta
      solvent closely resemble those of ideal polymers. In the semidilute regime,
      however, significant differences are found.

PMID- 15260585
TI  - Assignment of photoelectron spectra of AunO2- (n=2,4,6) clusters.

PMID- 15260586
TI  - Evidence for a bound HeH2 halo molecule by diffraction from a transmission
      grating.
AB  - The HeH2 van der Waals complex has been identified in a molecular beam produced
      by a cryogenic (T0=24.7 K) free jet expansion of a 1% H2 mixture in 99% 4He gas.
      The weakly bound HeH2 complexes in the beam are identified via their first order
      diffraction angles after passing through a 100 nm period transmission grating. An
      electron impact mass spectrometer analysis of the diffraction patterns is used to
      discriminate against ion fragments of the constituent gas clusters.

PMID- 15260587
TI  - Exploring molecular complexity: conical intersections and NH3 photodissociation.
AB  - The role of conical intersections in the photodissociation of the A 1A2" state of
      NH3 is investigated using extended atomic basis sets and a configuration state
      function expansion of approximately 8.5 million terms. A previously unknown
      portion of the 1 1A-2 1A seam of conical intersections with only C(s) symmetry is
      located. This portion of the seam is readily accessible from the equilibrium
      geometry of the A 1A2" state. These conical intersections are expected to play a
      role in the competition between adiabatic and nonadiabatic pathways for NH3(A
      1A2") photodissociation.

PMID- 15260588
TI  - Tetrasulfur, S4: rotational spectrum, interchange tunneling, and geometrical
      structure.
AB  - The rotational spectrum of S4 has been observed for the first time in an
      electrical discharge through sulfur vapor. Two techniques have been used: Fourier
      transform microwave spectroscopy and long-path millimeter-wave absorption
      spectroscopy. Small, but systematic shifts of the measured transition frequencies
      of the normal isotopic species indicate that S4 has C2v symmetry but with a low
      lying transition state of D2h symmetry, yielding interchange tunneling at 14.1(2)
      kHz in its ground vibrational state. From the rotational constants of the normal
      and the single 34S isotopic species, an experimental (r0) structure has been
      derived: S4 is a singlet planar trapezoid with a terminal bond length of 1.899(7)
      A, a central bond of 2.173(32) A, and an S-S-S angle of 103.9(8) degrees. Like
      thiozone (S3), S4 is a candidate for detection in the atmosphere of the Jovian
      moon Io and in other astronomical sources.

PMID- 15260589
TI  - Higher order and infinite Trotter-number extrapolations in path integral Monte
      Carlo.
AB  - Improvements beyond the primitive approximation in the path integral Monte Carlo
      method are explored both in a model problem and in real systems. Two different
      strategies are studied: The Richardson extrapolation on top of the path integral
      Monte Carlo data and the Takahashi-Imada action. The Richardson extrapolation,
      mainly combined with the primitive action, always reduces the number-of-beads
      dependence, helps in determining the approach to the dominant power law behavior,
      and all without additional computational cost. The Takahashi-Imada action has
      been tested in two hard-core interacting quantum liquids at low temperature. The
      results obtained show that the fourth-order behavior near the asymptote is
      conserved, and that the use of this improved action reduces the computing time
      with respect to the primitive approximation.

PMID- 15260590
TI  - Cumulative isomerization probability studied by various transition state wave
      packet methods including the MCTDH algorithm. Benchmark: HCN-->CNH isomerization.
AB  - The 3D cumulative isomerization probability N(E) for the transfer of a light
      particle between two atoms is computed by one time-independent and two time
      dependent versions of the transition state wave packet (TSWP) method. The time
      independent method is based on the direct expansion of the microcanonical
      projection operator on Chebyshev polynomials. In the time-dependent TSWP methods,
      the propagations are carried out by the split operator scheme and the
      multiconfiguration time-dependent Hartree (MCTDH) algorithm. This is the very
      first implementation of the TSWP method in the Heidelberg MCTDH package [G. W.
      Worth, M. H. Beck, A. Jackle, and H.-D. Meyer, The MCDTH package, Version 8.2
      (2000); H.-D Meyer, Version 8.3 (2002). See http://www.pci.uni
      heidelberg.de/tc/usr/mctdh/]. The benchmark is the HCN-->CNH isomerization for
      zero total angular momentum. Particular insights are given into the tunneling
      region. In larger systems, the time-dependent version of TSWP making use of the
      MCTDH algorithm will permit to treat more and more modes quantum mechanically,
      for very accurate results. Therefore, it was important to calibrate the
      implementation. Besides, we also assess the efficiency of a reduced
      dimensionality approach by comparing the new exact 3D calculations of N(E) for
      the HCN-->CNH isomerization with results obtained via 1D or 2D active subspaces.
      This suggests that, it should be possible to take directly benefit of the present
      3D approaches, adapted for triatomic Jacobi coordinates to compute N(E) for H
      transfer in larger systems, via three active coordinates. The prerequisite is
      then the simplification of the reduced 3D kinetic energy operator with rigid
      constraint to take the form corresponding to a pseudo triatomic system in Jacobi
      coordinates with effective masses. This last step is checked in the methoxy
      radical and malonaldehyde. Finally, different ways to obtain reliable
      eigenvectors of the flux operator associated with a dividing surface are
      revisited.

PMID- 15260591
TI  - Asymptotic correction of the exchange-correlation kernel of time-dependent
      density functional theory for long-range charge-transfer excitations.
AB  - Time-dependent density functional theory (TDDFT) calculations of charge-transfer
      excitation energies omegaCT are significantly in error when the adiabatic local
      density approximation (ALDA) is employed for the exchange-correlation kernel fxc.
      We relate the error to the physical meaning of the orbital energy of the Kohn
      Sham lowest unoccupied molecular orbital (LUMO). The LUMO orbital energy in Kohn
      Sham DFT--in contrast to the Hartree-Fock model--approximates an excited
      electron, which is correct for excitations in compact molecules. In CT
      transitions the energy of the LUMO of the acceptor molecule should instead
      describe an added electron, i.e., approximate the electron affinity. To obtain a
      contribution that compensates for the difference, a specific divergence of fxc is
      required in rigorous TDDFT, and a suitable asymptotically correct form of the
      kernel fxc(asymp) is proposed. The importance of the asymptotic correction of fxc
      is demonstrated with the calculation of omegaCT(R) for the prototype diatomic
      system HeBe at various separations R(He-Be). The TDDFT-ALDA curve omegaCT(R)
      roughly resembles the benchmark ab initio curve omegaCT CISD(R) of a
      configuration interaction calculation with single and double excitations in the
      region R=1-1.5 A, where a sizable He-Be interaction exists, but exhibits the
      wrong behavior omegaCT(R)<<omegaCT CISD(R) at large R. The TDDFT curve obtained
      with fxc (asymp) however approaches omegaCT CISD(R) closely in the region R=3-10
      A. Then, the adequate rigorous TDDFT approach should interpolate between the
      LDA/GGA ALDA xc kernel for excitations in compact systems and fxc(asymp) for
      weakly interacting fragments and suitable interpolation expressions are
      considered.

PMID- 15260592
TI  - Dissipative quantum dynamics with the surrogate Hamiltonian approach. A
      comparison between spin and harmonic baths.
AB  - The dissipative quantum dynamics of an anharmonic oscillator coupled to a bath is
      studied with the purpose of elucidating the differences between the relaxation to
      a spin bath and to a harmonic bath. Converged results are obtained for the spin
      bath by the surrogate Hamiltonian approach. This method is based on constructing
      a system-bath Hamiltonian, with a finite but large number of spin bath modes,
      that mimics exactly a bath with an infinite number of modes for a finite time
      interval. Convergence with respect to the number of simultaneous excitations of
      bath modes can be checked. The results are compared to calculations that include
      a finite number of harmonic modes carried out by using the multiconfiguration
      time-dependent Hartree method of Nest and Meyer [J. Chem. Phys. 119, 24 (2003)].
      In the weak coupling regime, at zero temperature and for small excitations of the
      primary system, both methods converge to the Markovian limit. When initially the
      primary system is significantly excited, the spin bath can saturate restricting
      the energy acceptance. An interaction term between bath modes that spreads the
      excitation eliminates the saturation. The loss of phase between two cat states
      has been analyzed and the results for the spin and harmonic baths are almost
      identical. For stronger couplings, the dynamics induced by the two types of baths
      deviate. The accumulation and degree of entanglement between the bath modes have
      been characterized. Only in the spin bath the dynamics generate entanglement
      between the bath modes.

PMID- 15260593
TI  - Classical spin and quantum-mechanical descriptions of geometric spin frustration.
AB  - Geometric spin frustration (GSF) in isolated plaquettes with local spin s, i.e.,
      an equilateral-triangle spin trimer and a regular-tetrahedron spin tetramer, was
      examined on the basis of classical spin and quantum-mechanical descriptions to
      clarify their differences and similarities. An analytical proof was given for how
      the state degeneracy and the total spin S of their ground states depend on the
      local spin s. The quantum-mechanical conditions for the occurrence of GSF in
      isolated plaquettes were clarified, and their implications were explored. Corner
      sharing between plaquettes and how it affects GSF in the resulting spin systems
      was examined.

PMID- 15260594
TI  - Efficient and reliable numerical integration of exchange-correlation energies and
      potentials.
AB  - An adaptive numerical integrator for the exchange-correlation energy and
      potential is presented. It uses the diagonal elements of the exchange-correlation
      potential matrix as a grid generating function. The only input parameter is the
      requested grid tolerance. In combination with a defined cell function the
      adaptive grid generation scales almost linear with the number of basis functions
      in a system. With the adaptive numerical integrator the self-consistent field
      energy error, which is due to the numerical integration of the exchange
      correlation energy, converges with increasing adaptive grid size to a reference
      value. The performance of the adaptive numerical integration is analyzed using
      molecules with first, second, and third row elements. Especially for transition
      metal systems the adaptive numerical integrator shows considerably improved
      performance and reliability.

PMID- 15260595
TI  - Potential energy surface discontinuities in local correlation methods.
AB  - We have examined the occurrence of discontinuities in bond-breaking potential
      energy surfaces given by local correlation methods based on the Pulay-Saebo
      orbital domain approach. Our analysis focuses on three prototypical dissociating
      systems: the C-F bond in fluoromethane, the C-C bond in singlet, ketene, and the
      central C-C bond in propadienone. We find that such discontinuities do not occur
      in cases of homolytic bond cleavage due to the inability of the Pipek-Mezey
      orbital localization method to separate singlet-coupled charges on distant
      fragments. However, for heterolytic bond cleavage, such as that observed in
      singlet ketene and propadienone, discontinuities occur both at stretched
      geometries and near equilibrium. These discontinuities are usually small, but may
      be of the same order of magnitude as the localization error in some cases.

PMID- 15260596
TI  - Parallel iterative reaction path optimization in ab initio quantum
      mechanical/molecular mechanical modeling of enzyme reactions.
AB  - The determination of reaction paths for enzyme systems remains a great challenge
      for current computational methods. In this paper we present an efficient method
      for the determination of minimum energy reaction paths with the ab initio quantum
      mechanical/molecular mechanical approach. Our method is based on an adaptation of
      the path optimization procedure by Ayala and Schlegel for small molecules in gas
      phase, the iterative quantum mechanical/molecular mechanical (QM/MM) optimization
      method developed earlier in our laboratory and the introduction of a new metric
      defining the distance between different structures in the configuration space. In
      this method we represent the reaction path by a discrete set of structures. For
      each structure we partition the atoms into a core set that usually includes the
      QM subsystem and an environment set that usually includes the MM subsystem. These
      two sets are optimized iteratively: the core set is optimized to approximate the
      reaction path while the environment set is optimized to the corresponding energy
      minimum. In the optimization of the core set of atoms for the reaction path, we
      introduce a new metric to define the distances between the points on the reaction
      path, which excludes the soft degrees of freedom from the environment set and
      includes extra weights on coordinates describing chemical changes. Because the
      reaction path is represented by discrete structures and the optimization for each
      can be performed individually with very limited coupling, our method can be
      executed in a natural and efficient parallelization, with each processor handling
      one of the structures. We demonstrate the applicability and efficiency of our
      method by testing it on two systems previously studied by our group,
      triosephosphate isomerase and 4-oxalocrotonate tautomerase. In both cases the
      minimum energy paths for both enzymes agree with the previously reported paths.

PMID- 15260597
TI  - Quantum-classical dynamics of scattering processes in adiabatic and diabatic
      representations.
AB  - We demonstrate the workability of a TDDVR based [J. Chem. Phys. 118, 5302
      (2003)], novel quantum-classical approach, for simulating scattering processes on
      a quasi-Jahn-Teller model [J. Chem. Phys. 105, 9141 (1996)] surface. The
      formulation introduces a set of DVR grid points defined by the Hermite part of
      the basis set in each dimension and allows the movement of grid points around the
      central trajectory. With enough trajectories (grid points), the method converges
      to the exact quantum formulation whereas with only one grid point, we recover the
      conventional molecular dynamics approach. The time-dependent Schrodinger equation
      and classical equations of motion are solved self-consistently and electronic
      transitions are allowed anywhere in the configuration space among any number of
      coupled states. Quantum-classical calculations are performed on diabatic surfaces
      (two and three) to reveal the effects of symmetry on inelastic and reactive state
      to-state transition probabilities, along with calculations on an adiabatic
      surface with ordinary Born-Oppenheimer approximation. Excellent agreement between
      TDDVR and DVR results is obtained in both the representations.

PMID- 15260598
TI  - Non-Hermitian quantum mechanics: wave packet propagation on autoionizing
      potential energy surfaces.
AB  - The correspondence between the time-dependent and time-independent molecular
      dynamic formalisms is shown for autoionizing processes. We demonstrate that the
      definition of the inner product in non-Hermitian quantum mechanics plays a key
      role in the proof. When the final state of the process is dissociative, it is
      technically favorable to introduce a complex absorbing potential into the
      calculations. The conditions which this potential should fulfill are briefly
      discussed. An illustrative numerical example is presented involving three
      potential energy surfaces.

PMID- 15260599
TI  - A multidimensional discrete variable representation basis obtained by
      simultaneous diagonalization.
AB  - Direct product basis functions are frequently used in quantum dynamics
      calculations, but they are poor in the sense that many such functions are
      required to converge a spectrum, compute a rate constant, etc. Much better,
      contracted, basis functions, that account for coupling between coordinates, can
      be obtained by diagonalizing reduced dimension Hamiltonians. If a direct product
      basis is used, it is advantageous to use discrete variable representation (DVR)
      basis functions because matrix representations of functions of coordinates are
      diagonal in the DVR. By diagonalizing matrices representing coordinates it is
      straightforward to obtain the DVR that corresponds to any direct product basis.
      Because contracted basis functions are eigenfunctions of reduced dimension
      Hamiltonians that include coupling terms they are not direct product functions.
      The advantages of contracted basis functions and the advantages of the DVR
      therefore appear to be mutually exclusive. A DVR that corresponds to contracted
      functions is unknown. In this paper we propose such a DVR. It spans the same
      space as a contracted basis, but in it matrix representations of coordinates are
      diagonal. The DVR basis functions are chosen to achieve maximal diagonality of
      coordinate matrices. We assess the accuracy of this DVR by applying it to model
      four-dimensional problems.

PMID- 15260600
TI  - Analytical energy gradients for local second-order Moller-Plesset perturbation
      theory using density fitting approximations.
AB  - An efficient method to compute analytical energy derivatives for local second
      order Moller-Plesset perturbation energy is presented. Density fitting
      approximations are employed for all 4-index integrals and their derivatives.
      Using local fitting approximations, quadratic scaling with molecular size and
      cubic scaling with basis set size for a given molecule is achieved. The density
      fitting approximations have a negligible effect on the accuracy of optimized
      equilibrium structures or computed energy differences. The method can be applied
      to much larger molecules and basis sets than any previous second-order Moller
      Plesset gradient program. The efficiency and accuracy of the method is
      demonstrated for a number of organic molecules as well as for molecular clusters.
      Examples of geometry optimizations for molecules with 100 atoms and over 2000
      basis functions without symmetry are presented.

PMID- 15260601
TI  - Density functional theory study of H and H2 interacting with NiAl(110).
AB  - We present results of extensive density functional theory (DFT) calculations for
      H and H2 interacting with NiAl(110). Continuous representations of the full
      dimensional potential energy surface (PES) for the H/NiAl(110) and H2/NiAl(110)
      systems are obtained by interpolation of the DFT results using the corrugation
      reducing procedure. We find a minimum activation energy barrier of approximately
      300 meV for dissociative adsorption of H2, which is consistent with the energy
      threshold obtained in molecular beam experiments for H2 (nu=0). We explain
      vibrational enhancement observed in experiments as the consequence of vibrational
      softening in the entrance channel over the most reactive surface site. The
      H2/NiAl(110) PES shows a high surface site selectivity: for energies up to 0.1 eV
      above threshold, H2 adsorption can only take place around top-Ni sites (within a
      circle of radius approximately 0.3 A). A strong energetic corrugation is
      observed: energy barriers for dissociation vary by more than 1 eV between the
      most and the least reactive sites. In contrast, geometric corrugation is much
      less pronounced and comparable to that of low index single metal surfaces like Cu
      or Pt.

PMID- 15260603
TI  - Selective infrared photodissociation of protonated para-fluorophenol isomers:
      substitution effects in oxonium and fluoronium ions.
AB  - Isomer-selective infrared photodissociation (IRPD) spectra are obtained for the
      first time for protonated polyfunctional aromatic molecules isolated in the gas
      phase. IRPD spectra of the oxonium and fluoronium isomers of protonated para
      fluorophenol (C6H6FO+) were separately obtained by monitoring resonant photo
      induced H2O and HF loss, respectively. Analysis of the F-H, O-H, and C-H stretch
      wave numbers provides valuable spectroscopic information on the chemical
      properties of these reactive intermediates, in particular on the substitution
      effects of functional groups.

PMID- 15260602
TI  - A simple model for NMR relaxation in the presence of internal motions with
      dynamical coupling.
AB  - In this paper some effects of dynamical coupling between two interaction-carrying
      vectors on the internal auto- and cross-correlation functions are investigated in
      the limit of small amplitude motions. A linearized Langevin approach allows the
      derivation of explicit expressions for these correlation functions and for the
      corresponding order parameters.

PMID- 15260604
TI  - Free energy perturbation study of water dimer dissociation kinetics.
AB  - An efficient approach is described for using accurate ab initio calculations to
      determine the rates of elementary condensation and evaporation processes that
      lead to nucleation of aqueous aerosols. The feasibility of the method is
      demonstrated in an application to evaporation rates of water dimer at 230 K. The
      method, known as ABC-FEP (ab initio/classical free energy perturbation), begins
      with a calculation of the potential of mean force for the dissociation
      (evaporation) of small water clusters using a molecular dynamics (MD) simulation
      with a model potential. The free energy perturbation is used to calculate how
      changing from the model potential to a potential calculated from ab initio
      methods would alter the potential of mean force. The difference in free energy is
      the Boltzmann-weighted average of the difference between the ab initio and
      classical potential energies, with the average taken over a sample of
      configurations from the MD simulation. In principle, the method does not require
      a highly accurate model potential, though more accurate potentials require fewer
      configurations to achieve a small sampling error in the free energy perturbation
      step. To test the feasibility of obtaining accurate potentials of mean force from
      ab initio calculations at a modest number of configurations, the free energy
      perturbation method has been used to correct the errors when some standard models
      for bulk water (SPC, TIP4P, and TIP4PFQ) are applied to water dimer. To allow a
      thorough exploration of sampling issues, a highly accurate fit to results of
      accurate ab initio calculations, known as SAPT-5s, as been used a proxy for the
      ab initio calculations. It is shown that accurate values for a point on the
      potential of mean force can be obtained from any of the water models using ab
      initio calculations at only 50 configurations. Thus, this method allows accurate
      simulations of small clusters without the need to develop water models
      specifically for clusters.

PMID- 15260605
TI  - On the interconversion pathway of HBO<-->BOH.
AB  - The potential energy surfaces have been constructed for the 1A', 3A', and 3A"
      states of HBO by using the multireference perturbation theory with the basis set
      cc-pVTZ (6d,10f). Two stationary points and a transition state have been
      characterized on all the three surfaces, which are in good agreement with
      available experiments and previous calculations. The interconversion pathways
      from metastable boron hydroxide BOH to the considerably more stable HBO are
      expounded based on the nature of the surfaces.

PMID- 15260606
TI  - Nonadiabatic alignment of asymmetric top molecules: rotational revivals.
AB  - The rotational revival structure of asymmetric top molecules, following
      irradiation by an intense picosecond laser pulse, is explored theoretically and
      experimentally. Numerically we solve nonperturbatively for the rotational
      dynamics of a general asymmetric top subject to a linearly polarized intense
      pulse, and analyze the dependence of the dynamical alignment on the field and
      system parameters. Experimentally we use time-resolved photofragment imaging to
      measure the alignment of two molecules with different asymmetry, iodobenzene, and
      iodopentafluorobenzene. Our numerical results explain the experimental
      observations and generalize them to other molecules. The rotational revival
      structure of asymmetric tops differs qualitatively from the intensively studied
      linear top case. Potentially it provides valuable structural information about
      molecules.

PMID- 15260607
TI  - Autoionization and neutral dissociation of superexcited HI studied by two
      dimensional photoelectron spectroscopy.
AB  - Two-dimensional photoelectron spectroscopy of hydrogen iodide (HI) has been
      performed in the photon energy region of 11.10-14.85 eV, in order to investigate
      dynamical properties on autoionization and neutral dissociation of Rydberg states
      HI*(RA) converging to HI+(A 2Sigma1/2(+)). A two-dimensional photoelectron
      spectrum exhibits strong vibrational excitation of HI+(X 2Pi) over a photon
      energy region from approximately 12 to 13.7 eV, which is attributable to the
      autoionizing feature of the 5 dpi HI*(RA) state. A noticeable set of stripes in
      the photon energy region of 13.5-14.5 eV is assigned as resulting from
      autoionization of the atomic Rydberg states of I* converging to I+ (3P0 or 3P1).
      The formation of I* is understood in terms of predissociation of multiple HI*(RA)
      states by way of the repulsive Rydberg potential curves converging to
      HI+(4Pi1/2).

PMID- 15260608
TI  - Some symmetry-induced isotope effects in the kinetics of recombination reactions.
AB  - Symmetry-induced isotope effects in recombination and collision-induced
      dissociation reactions are discussed. Progress on understanding the anomalous
      isotope effects in ozone is reviewed. Then, calculations are performed for the
      simpler reaction xNe+yNe+H<-->xNeyNe+H, where x and y label either identical or
      different isotopes. The atomic masses in the model are chosen so that symmetry is
      the only difference between the systems. Starting from a single potential energy
      surface, the properties of the bound, quasibound, and continuum states of the
      neon dimer are calculated. Then, the vibration rotation infinite order sudden
      approximation is used to calculate cross sections for all possible inelastic and
      dissociative processes. A rate constant matrix that exactly satisfies detailed
      balance is constructed. It allows recombination to occur both via direct three
      body collisions and via tunneling into the quasibound states of the energy
      transfer mechanism. The eigenvalue rate coefficients are determined. Significant
      isotope effects are clearly found, and their behavior depends on the pressure,
      temperature, and mechanism of the reaction. Both spin statistics and symmetry
      breaking produce isotope effects. Under most conditions the breaking of symmetry
      enhances the rates, but a wide spectrum of effects is observed; they range from
      isotope effects with a normal mass dependence to huge, mass-independent isotope
      effects to cancellation and even to reversal of the isotope effects. This is the
      first calculation of symmetry-induced isotope effects in recombination rates from
      first principles. The relevance of the present effects to ozone recombination is
      discussed.

PMID- 15260609
TI  - Observation of a reactive resonance in the integral cross section of a six-atom
      reaction: F+CHD3.
AB  - The title reaction was investigated under crossed-beam conditions at collisional
      energies ranging from about 0.4 to 7.5 kcal/mol. Product velocity distributions
      were measured by a time-sliced, velocity-map imaging technique to explicitly
      account for the density-to-flux transformation factors. Both the state-resolved,
      pair-correlated excitation functions and vibrational branching ratios are
      presented for the two isotopic product channels. An intriguing resonance
      tunneling mechanism occurring near the reaction threshold for the HF+CD3 product
      channel is surmized, which echoes the reactive resonances found previously for
      the F+HD-->HF+D reaction and more recently for the F+CH4 reaction.

PMID- 15260610
TI  - The role of dimers in evaporation of small argon clusters.
AB  - Evaporation of small Lennard-Jones argon clusters has been studied using
      molecular dynamic simulations. An extensive library of clusters with 4, 5, 6, 11,
      and 21 atoms has been obtained from an earlier study. Analysis of the evaporation
      properties of the clusters indicate, that the fraction of dimer evaporations of
      all evaporation events increases with the total energy of the cluster. The
      fraction of evaporated dimers from clusters with a constant lifetime is
      independent of the cluster size for short-lived clusters and increases with
      cluster size for long-lived clusters. Only a few percent of the clusters which
      are long lived enough to participate in vapor-liquid nucleation decay by emitting
      dimers. The mean cluster lifetime as a function of total energy shows the same
      exponentially decreasing trend for monomer and dimer evaporation channels. The
      fraction of trimer evaporations is found to be vanishingly small.

PMID- 15260611
TI  - Quantum dynamics of vibrationally activated OH-CO reactant complexes.
AB  - A six-dimensional wave packet study of the unimolecular decay of vibrationally
      activated OH-CO reactant channel complexes is presented. The ab initio based
      Lakin-Troya-Schatz-Harding potential energy functions for the A' and A" states
      are employed. Good agreement with the experimental product distributions and
      lifetimes of Pond and Lester is found. We are able to confirm that complexes with
      two vibrational quanta of excitation in OH, vOH=2, and no vibrational excitation
      in CO, vCO=0, decay through two pathways. One pathway leads to products (vOH=1,
      vCO=0) with relatively high OH rotational energy and the other leads to products
      (vOH=1, vCO=1) with relatively low OH rotational energy. We also find that the
      lifetime of the A" state is less than the A' state and that there is a propensity
      for A" products.

PMID- 15260612
TI  - The permanent electric dipole moments of calcium monohydride, CaH.
AB  - Numerous branch features in the (0,0) A 2Pi-X 2Sigma+ band system of calcium
      monohydride CaH have been studied by optical Stark spectroscopy. The Stark
      shifts, Stark splittings, and appearance of electric-field-induced transitions in
      the high resolution laser-induced fluorescence spectra are analyzed to produce
      values for the magnitude of the permanent electric dipole moments mid R:micromid
      R: of 2.94(16) D and 2.372(12) D for the X 2Sigma+(v=0) and A 2Pi(v=0) states,
      respectively. A comparison with values predicted from a semiempirical
      electrostatic model and previous ab initio calculations for mid R:micromid R: (X
      2Sigma+) is presented. The change in mid R:micromid R: upon excitation from the X
      2Sigma+ state to the A 2Pi state is rationalized using a simple molecular orbital
      description.

PMID- 15260613
TI  - A combined experimental and computational investigation of the microscopic
      external heavy atom effect in van der Waals clusters.
AB  - We present a combined experimental and computational study of the external heavy
      atom effect in van der Waals clusters of para-difluorobenzene (pDFB) with rare
      gas atoms. Experimentally, clustering with rare-gas atoms is observed to shorten
      significantly the S1 fluorescence lifetime compared with that of the pDFB
      monomer, an effect we interpret in terms of an enhancement of the S1-T1
      intersystem crossing rate. In order to test the validity of this widely held
      assumption, we have calculated the S1-T1 spin-orbit coupling matrix elements in
      the X-pDFB complexes (X=Ne, Ar, Kr) using a multiconfigurational linear response
      approach.

PMID- 15260614
TI  - p-benzoquinone-benzene clusters as potential nanomechanical devices: a
      theoretical study.
AB  - The equilibrium structures and binding energies of the benzene complexes of p
      benzoquinones (PBQ) and its negatively charged anionic species (PBQ- and PBQ2-)
      have been investigated theoretically using second-order Moller-Plesset
      calculations. While neutral p-benzoquinone-benzene clusters (PBQ-Bz) prefer to
      have a parallel displaced geometry (P-c), CH...pi interactions (T-shaped
      geometries) prevail in the di-anionic PBQ-benzene (PBQ2- -Bz) complexes (T-e2-).
      Studies on dianionic p-benzoquinone-benzene clusters showed that two nonbonded
      intermolecular interactions compete in the most stable conformation. One is H
      bonding interaction (C-H...O type) between carbonyl oxygen of p-benzoquinone and
      one of the hydrogen atoms of benzene, and the other is a pi-H interaction between
      pi-electron cloud of PBQ2- and another hydrogen atom of benzene. Blueshifted H
      bonds were observed in T-shaped clusters. The changes in the geometrical
      preference of PBQ-Bz complex upon addition of electrons would be useful in
      designing optimized molecular mechanical devices based on the edge-to-face and
      face-to-face aromatic interactions.

PMID- 15260615
TI  - Taming the rugged landscape: production, reordering, and stabilization of
      selected cluster inherent structures in the X13-nYn system.
AB  - We present studies of the potential energy landscape of selected binary Lennard
      Jones 13 atom clusters. The effect of adding selected impurity atoms to a
      homogeneous cluster is explored. We analyze the energy landscapes of the studied
      systems using disconnectivity graphs. The required inherent structures and
      transition states for the construction of disconnectivity graphs are found by
      combination of conjugate gradient and eigenvector-following methods. We show that
      it is possible to controllably induce new structures as well as reorder and
      stabilize existing structures that are characteristic of higher-lying minima.
      Moreover, it is shown that the selected structures can have experimentally
      relevant lifetimes.

PMID- 15260616
TI  - Phase changes in selected Lennard-Jones X13-nYn clusters.
AB  - Detailed studies of the thermodynamic properties of selected binary Lennard-Jones
      clusters of the type X13-nYn (where n=1, 2, 3) are presented. The total energy,
      heat capacity, and first derivative of the heat capacity as a function of
      temperature are calculated by using the classical and path integral Monte Carlo
      methods combined with the parallel tempering technique. A modification in the
      phase change phenomena from the presence of impurity atoms and quantum effects is
      investigated.

PMID- 15260617
TI  - Exact solution of the excited-state geminate A*+B <==> C*+D reaction with two
      different lifetimes and quenching.
AB  - The authors obtain, in the Laplace transform space, the exact analytic solution
      for the Green function and survival probabilities for the excited-state diffusion
      influenced reversible geminate reaction, A*+B <==> C*+D, with two different
      lifetimes and in the presence of an added quenching process. This extends a
      previous investigation by Popov and Agmon [J. Chem. Phys. 117, 5770 (2002)] of
      the ground-state reaction without quenching. The long-time asymptotic behavior of
      the survival probabilities is obtained in the time domain. It is found to be
      different from the equal-lifetime case. This paper also provides a useful short
      time approximation for the kinetics.

PMID- 15260618
TI  - Fifth-order contributions to ultrafast spectrally resolved vibrational echoes:
      heme-CO proteins.
AB  - The fifth order contributions to the signals of ultrafast infrared spectrally
      resolved stimulated vibrational echoes at high intensities have been investigated
      in carbonmonoxy heme proteins. High intensities are often required to obtain good
      data. Intensity dependent measurements are presented on hemoglobin-CO (Hb-CO) and
      a mutant of myoglobin, H64V-CO. The spectrally resolved vibrational echoes
      demonstrate that fifth order effects arise at both the 1-0 and the 2-1 emission
      frequencies of the stretching mode of the CO chromophore bound at the active site
      of heme proteins. Unlike one-dimensional experiments, in which the signal is
      integrated over all emission frequencies, spectrally resolving the signal shows
      that the fifth order contributions have a much more pronounced influence on the 2
      1 transition than on the 1-0 transition. By spectrally isolating the 1-0
      transition, the influence of fifth order contributions to vibrational echo data
      can be substantially reduced. Analysis of fifth order Feynman diagrams that
      contribute in the vibrational echo phase-matched direction demonstrates the
      reason for the greater influence of fifth order processes on the 1-2 transition,
      and that the fifth order contributions are heterodyne amplified by the third
      order signal. Finally, it is shown that the anharmonic oscillations in
      vibrational echo data of Hb-CO that previous work had attributed strictly to
      fifth order effects arise even without fifth order contributions.

PMID- 15260619
TI  - Enhancement of the recollision rate in diffusion-influenced reactions in an
      inhomogeneous medium.
AB  - Brownian dynamics simulations were performed to determine the first collision and
      recollision rates of spherical reagent particles in a reaction medium made
      heterogeneous by the presence of randomly located inert spherical obstacles in a
      continuum solvent. The recollision rate vp (and hence the overall reactive
      collision rate when activation energy is high) was always enhanced by the
      presence of obstacles, the degree of enhancement increasing with the volume
      fraction occupied by obstacles (phi) and with decreasing reagent concentration
      phiR. Enhancement increased with obstacle size at high phiR, and fell with
      increasing obstacle size at low phiR. The vp-phiR data follow a power law, where
      the scaling factor betap decreased with decreasing obstacle size and increasing
      phi, and the prefactor kp initially increased with phi and then fell (except for
      large obstacles). The behavior of betap appears to be largely due to the
      obstacles reducing the probability that reagent particles escape from each other
      after collision, while the dominant factors responsible for the behavior of kp
      appear to be initially the effect of obstacles in enhancing effective local
      reagent concentration, and then (for small obstacles), their reduction of the
      reagent-particle coordination number. As the energy of activation falls, the
      reactive collision rate becomes less influenced by the reagent recollision rate
      and more influenced by the rate of first collision. For low-activation-energy
      reactions, the presence of obstacles depresses the reactive collision rate if
      reagent concentration is low or if the obstacles are small and their
      concentration high. The fall in the reactive collision rate with decreasing
      activation energy is steeper, the lower the reagent concentration and the smaller
      the obstacles.

PMID- 15260620
TI  - Subcritical wave instability in reaction-diffusion systems.
AB  - We report an example of subcritical wave instability in a model of a reaction
      diffusion system and discuss the potential implications for localized patterns
      found in experiments on the Belousov-Zhabotinsky reaction in a microemulsion.

PMID- 15260621
TI  - Application of Lagrangian theorem-based density-functional approximation free of
      adjustable parameters to nonhard-sphere fluid.
AB  - A recently proposed parameter free version of a Lagrangian theorem-based density
      functional approximation (LTDFA) [S. Zhou, Phys. Lett. A 319, 279 (2003)] for
      hard-sphere fluid is applied to hard-core attractive Yukawa model fluid by
      dividing bulk second-order direct correlation function (DCF) of fluid under
      consideration into hard-core part and tail part. The former is treated by the
      parameter free version of the LTDFA, while the tail part is treated by second
      order functional perturbation expansion approximation as done in a recent
      partitioned DFA [S. Zhou, Phys. Rev. E 68, 061201 (2003)]. Two versions of mean
      spherical approximation (MSA) for the bulk second-order DCF are employed as
      input, one is the less accurate plain MSA whose tail part of the second-order DCF
      is strictly independent of a density argument, the other is the more accurate
      inverse temperature expansion version of the MSA whose tail part is not strictly
      independent of the density argument. Calculational results indicate that
      prediction based on the plain MSA is far more accurate than that based on the
      inverse temperature expansion version of the MSA. The reason is considered to be
      that the partitioned DFA requires that the tail part is highly or completely
      independent of the density argument, the plain MSA, by assuming that the tail
      part is exactly the potential itself, embodies all of the nonlinearities into the
      hard-core part which can be treated satisfactorily by the parameter free version
      of the LTDFA. The present investigation results in a universal method for
      constructing DFA for nonuniform any nonhard-sphere interaction potential fluids.

PMID- 15260622
TI  - Coherent low-frequency motions of hydrogen bonded acetic acid dimers in the
      liquid phase.
AB  - Ultrafast vibrational dynamics of cyclic hydrogen bonded dimers and the
      underlying microscopic interactions are studied in temporally and spectrally
      resolved pump-probe experiments with 100 fs time resolution. Femtosecond
      excitation of the O-H and/or O-D stretching mode gives rise to pronounced changes
      of the O-H/O-D stretching absorption displaying both rate-like kinetic and
      oscillatory components. A lifetime of 200 fs is measured for the v=1 state of the
      O-H stretching oscillator. The strong oscillatory absorption changes are due to
      impulsively driven coherent wave packet motions along several low-frequency modes
      of the dimer between 50 and 170 cm(-1). Such wave packets generated via coherent
      excitation of the high-frequency O-H/O-D stretching oscillators represent a clear
      manifestation of the anharmonic coupling of low- and high-frequency modes. The
      underdamped low-frequency motions dephase on a time scale of 1-2 ps. Calculations
      of the vibrational potential energy surface based on density functional theory
      give the frequencies, anharmonic couplings, and microscopic elongations of the
      low-frequency modes, among them intermolecular hydrogen bond vibrations.
      Oscillations due to the excitonic coupling between the two O-H or O-D stretching
      oscillators are absent as is independently confirmed by experiments on mixed
      dimers with uncoupled O-H and O-D stretching oscillators.

PMID- 15260623
TI  - Monte Carlo simulations of critical cluster sizes and nucleation rates of water.
AB  - We have calculated the critical cluster sizes and homogeneous nucleation rates of
      water at temperatures and vapor densities corresponding to experiments by Wolk
      and Strey [J. Phys. Chem B 105, 11683 (2001)]. The calculations have been done
      with an expanded version of a Monte Carlo method originally developed by
      Vehkamaki and Ford [J. Chem. Phys. 112, 4193 (2000)]. Their method calculates the
      statistical growth and decay probabilities of molecular clusters. We have derived
      a connection between these probabilities and kinetic condensation and evaporation
      rates, and introduce a new way for the calculation of the work of formation of
      clusters. Three different interaction potential models of water have been used in
      the simulations. These include the unpolarizable SPC/E [J. Phys. Chem. 91, 6269
      (1987)] and TIP4P [J. Chem. Phys. 79, 926 (1983)] models and a polarizable model
      by Guillot and Guissani [J. Chem. Phys. 114, 6720 (2001)]. We show that TIP4P
      produces critical cluster sizes and a temperature and vapor density dependence
      for the nucleation rate that agree well with the experimental data, although the
      magnitude of nucleation rate is constantly overestimated by a factor of 2 x
      10(4). Guissani and Guillot's model is somewhat less successful, but both the
      TIP4P and Guillot and Guissani models are able to reproduce a much better
      experimental temperature dependency of the nucleation rate than the classical
      nucleation theory. Using SPC/E results in dramatically too small critical
      clusters and high nucleation rates. The water models give different average
      binding energies for clusters. We show that stronger binding between cluster
      molecules suppresses the decay probability of a cluster, while the growth
      probability is not affected. This explains the differences in results from
      different water models.

PMID- 15260624
TI  - "Cooperativity blockage" in the mixed alkali effect as revealed by molecular
      dynamics simulations of alkali metasilicate glass.
AB  - The relaxation dynamics of a complex interacting system can be drastically
      changed when mixing with another component having different dynamics. In this
      work, we elucidate the effect of the less mobile guest ions on the dynamics of
      the more mobile host ions in mixed alkali glasses by molecular-dynamics (MD)
      simulations. One MD simulation was carried out on lithium metasilicate glass with
      the guest ions created by freezing some randomly chosen lithium ions at their
      initial locations at 700 K. A remarkable slowing down of the dynamics of the
      majority mobile Li ions was observed both in the self-part of the density-density
      correlation function, Fs(k,t), and in the mean-squared displacements. On the
      other hand, there is no significant change in the structure. The motion of the Li
      ions in the unadulterated Li metasilicate glass is dynamically heterogeneous. In
      the present work, the fast and slow ions were divided into two groups. The number
      of fast ions, which shows faster dynamics (Levy flight) facilitated by
      cooperative jumps, decreases considerably when small amount of Li ions are
      frozen. Consequently there is a large overall reduction of the mobility of the Li
      ions. The result is also in accordance with the experimental finding in mixed
      alkali silicate glasses that the most dramatic reduction of ionic conductivity
      occurs in the dilute foreign alkali limit. Similar suppression of the cooperative
      jumps is observed in the MD simulation data of mixed alkali system, LiKSiO3.
      Naturally, the effect found here is appropriately described as "cooperativity
      blockage." Slowing down of the motion of Li ions also was observed when a small
      number of oxygen atoms chosen at random were frozen. The effect is smaller than
      the case of freezing some the Li ions, but it is not negligible. The
      cooperativity blockage is also implemented by confining the Li metasilicate glass
      inside two parallel walls formed by freezing Li ions in the same metasilicate
      glass. Molecular-dynamics simulations were performed on the dynamics of the Li
      ions in the confined glass. Slowing down of the dynamics is largest near the wall
      and decreases monotonically with distance away from the wall.

PMID- 15260625
TI  - Dispersion relations for the convective instability of an acidity front in Hele
      Shaw cells.
AB  - Autocatalytic chemical fronts of the chlorite-tetrathionate (CT) reaction become
      buoyantly unstable when they travel downwards in the gravity field because they
      imply an unfavorable density stratification of heavier products on top of lighter
      reactants. When such a density fingering instability occurs in extended Hele-Shaw
      cells, several fingers appear at onset which can be characterized by dispersion
      relations giving the growth rate of the perturbations as a function of their wave
      number. We analyze here theoretically such dispersion curves comparing the
      results for various models obtained by coupling Darcy's law or Brinkman's
      equation to either a one-variable reaction-diffusion model for the CT reaction or
      an eikonal equation. Our theoretical results are compared to recent experimental
      data.

PMID- 15260626
TI  - Viscosities of liquid CdTe near melting point from ab initio molecular-dynamics
      calculations.
AB  - Recent experimental results for the viscosity of liquid CdTe exhibit disparate
      behavior as a function of temperature. While some measurements show the expected
      Arrhenius-type behavior, other measurements show an anomalous temperature
      dependence indicating an increase in viscosity with increasing temperature. We
      present ab initio molecular-dynamics simulations of liquid cadmium telluride near
      its melting point and use the Stokes-Einstein relation to extract values of the
      viscosity constant. We find no anomalous behavior; the viscosity decreases
      monotonically with temperature and is consistent with an Arrhenius like behavior.
      Although calculated values are slightly smaller than those measured, the
      predicted activation energy agrees well with experiment.

PMID- 15260627
TI  - Chiral exciton wave functions in cylindrical J aggregates.
AB  - We study the exciton wave functions and the optical properties of cylindrical
      molecular aggregates. The cylindrical symmetry allows for a decomposition of the
      exciton Hamiltonian into a set of effective one-dimensional Hamiltonians,
      characterized by a transverse wave number k2. These effective Hamiltonians have
      interactions that are complex if the cylinder exhibits chirality. We propose
      analytical ansatze for the eigenfunctions of these one-dimensional problems that
      account for a finite cylinder length, and present a general study of their
      validity. A profound difference is found between the Hamiltonian for the
      transverse wave number k2=0 and those with k2 not equal 0. The complex nature of
      the latter leads to chiral wave functions, which we characterize in detail. We
      apply our general formalism to the chlorosomes of green bacteria and compare the
      wave functions as well as linear optical spectra (absorption and dichroism)
      obtained through our ansatze with those obtained by numerical diagonalization as
      well as those obtained by imposing periodic boundary conditions in the cylinder's
      axis direction. It is found that our ansatze, in particular, capture the finite
      length effect in the circular dichroism spectrum much better than the solution
      with periodic boundary conditions. Our ansatze also show that in finite-length
      cylinders seven superradiant states dominate the linear optical response.

PMID- 15260628
TI  - Noncatalytic kinetic study on site-selective H/D exchange reaction of phenol in
      sub- and supercritical water.
AB  - The site-selective H/D exchange reaction of phenol in sub- and supercritical
      water is studied without added catalysts. In subcritical water in equilibrium
      with steam at 210-240 degrees C, the H/D exchange proceeds both at the ortho and
      para sites in the phenyl ring, with no exchange observed at the meta site. The
      pseudo-first-order rate constants are of the order of 10(-4) s(-1); 50% larger
      for the ortho than for the para site. In supercritical water, the exchange is
      observed also at the meta site with the rate constant in the range of 10(-6)-10(
      4) s(-1). As the bulk density decreases, the exchange slows down and the site
      selectivity toward the ortho is enhanced. The enhancement is due to the phenol
      water interaction preference at the atomic resolution. The site selectivity
      toward the ortho is further enhanced when the reaction is carried out in
      benzene/water solution. Using such selectivity control and the reversible nature
      of the hydrothermal deuteration/protonation process, it is feasible to synthesize
      phenyl compounds that are deuterated at any topological combination of ortho,
      meta, and para sites.

PMID- 15260629
TI  - Tail molecule dependence of thiolate adsorption on Au(111) surface: Theoretical
      study.
AB  - The adsorption of thiolates with various tail molecules on the Au(111) surface
      has been investigated by first-principles calculations. We have considered six
      typical thiolate molecules, that is, methylthiolate, ethylthiolate,
      ethylenethiolate, acetylenethiolate, benzenethiolate, and thiophenethiolate. It
      is found that these thiolates exhibit little difference in their stable
      adsorption geometries. They are adsorbed at the bridge site with being
      significantly tilted from the surface normal. The adsorption energy of thiolate
      on Au, on the other hand, largely varies depending on the type of tail molecule,
      and is linearly proportional to the binding energy of thiolate with H. We discuss
      the tail molecule dependence in terms of the bonding environment around the C
      atom connected to the head S atom.

PMID- 15260630
TI  - Discrete solution of the electrokinetic equations.
AB  - We present a robust scheme for solving the electrokinetic equations. This goal is
      achieved by combining the lattice-Boltzmann method with a discrete solution of
      the convection-diffusion equation for the different charged and neutral species
      that compose the fluid. The method is based on identifying the elementary fluxes
      between nodes, which ensures the absence of spurious fluxes in equilibrium. We
      show how the model is suitable to study electro-osmotic flows. As an
      illustration, we show that, by introducing appropriate dynamic rules in the
      presence of solid interfaces, we can compute the sedimentation velocity (and
      hence the sedimentation potential) of a charged sphere. Our approach does not
      assume linearization of the Poisson-Boltzmann equation and allows us for a wide
      variation of the Peclet number.

PMID- 15260631
TI  - A Ti-V-based bcc phase alloy for use as metal hydride electrode with high
      discharge capacity.
AB  - The electrochemical characteristics of single bcc phase Ti-30V-15Cr-15Mn alloy
      were investigated. It was demonstrated that the single bcc phase alloy has high
      electrochemical discharge performance at high temperature. Its discharge capacity
      is closely related with temperature and discharge current. The first discharge
      capacities of 580-814 mAh g(-1) of the alloy powder were obtained at discharge
      current of 45-10 mA g(-1) in 6 M KOH solution at 353 K. Although the
      electrochemical cycle life of the alloy is unsatisfactory at present, it opens up
      prospects for developing a new hydrogen storage alloy with high hydrogen capacity
      for use as high performance metal hydride electrodes in rechargeable Ni-MH
      battery.

PMID- 15260632
TI  - Optical emission from C60-molecule-coupled Si nanocrystallites.
AB  - Using C60 molecule as a kind of surface-passivated agent to modify the electronic
      structure of Si nanocrystallites in porous silicon, we disclose that this kind of
      C60/nanocrystalline Si coupling system can show a strong blue emission at
      approximately 460 nm when stored in air for more than one year. After a full
      characterization of the photoluminescence properties, we propose a luminescent
      center in the SiOx layer at the surface of a Si nanocrystallite. It is a pair
      consisting of an oxygen vacancy and an interstitial oxygen. The interstitial
      oxygen also forms a peroxy linkage with a neighboring lattice oxygen. Radiative
      recombination of carriers photogenerated from Si nanocrystallite cores in the
      luminescent centers results in the observed blue photoluminescence. Neutron
      irradiation experiments support our assignment of the blue emission mechanism.
      This work improves the understanding of the origin of blue emission from
      silicon/oxygen-related nanostructured materials.

PMID- 15260633
TI  - The structure of calcium-ammonia solutions by neutron diffraction.
AB  - The microscopic structures of calcium-ammonia solutions have been established by
      using neutron diffraction. Total structure factors measured at 230 K reveal
      immediately the evolution of an uncommonly intense diffraction prepeak in the
      metallic solutions. As concentration is increased from 4 mole percent metal to 10
      mole percent metal (i.e., saturation), this feature intensifies and shifts from
      0.6 to 0.9 A(-1). It is therefore evidence of well developed intermediate-range
      ordering among the solvated cations, and is a microstructural signature of the
      observed strong phase separation of metallic (concentrated) and nonmetallic
      (dilute) solutions. The technique of isotopic labelling of *N by 15N was then
      used in conjunction with difference analysis to focus on the solvent structure in
      metallic solutions at 4 and 10 mole percent metal. These nitrogen-centered
      functions are analyzed in conjunction with classical Monte Carlo computer
      simulation techniques, to provide us with detailed insight into the calcium
      solvation and the extent of hydrogen bonding. We find that calcium is solvated by
      approximately 6-7 ammonia molecules, with a Ca-N distance of around 2.45 A. There
      is evidence of hydrogen bonding among the solvent molecules, even in the
      saturated 10 mole percent metal solution.

PMID- 15260634
TI  - The katoite hydrogarnet Si-free Ca3Al2([OH]4)3: a periodic Hartree-Fock and B3
      LYP study.
AB  - The structure of the Si-free katoite hydrogarnet (116 atoms in the unit cell) has
      been investigated at the periodic ab initio quantum mechanical level with the
      CRYSTAL program, by using a Gaussian type basis set and both the HF and the
      hybrid B3-LYP Hamiltonians. The structure has been fully optimized at various
      pressures in the 0-46 GPa range; the modifications of the structure, and in
      particular of the (OH)4 group, as a function of pressure are analyzed. At the B3
      LYP level and P greater than 15 GPa, a O-H...O interaction of increasing strength
      appears, with important modifications in the local geometry of the tetrahedral
      site. The calculated omega01(O-H) fundamental vibrational frequency at zero
      pressure is in excellent agreement with experiment (3674 and 3663 cm(-1),
      respectively); the omega01(O-H) stretching frequency remains essentially constant
      in the 0-15 GPa interval, whereas it dramatically decreases at higher pressures
      with a corresponding anharmonicity increase, as a consequence of the formation of
      a strong hydrogen bond. The hydration energy of grossular and the formation
      energy of Si-free katoite have also been computed, and the B3-LYP results are in
      quite good agreement with experiment.

PMID- 15260635
TI  - A density-functional study for the liquid-vapor coexistence curve of nitrogen
      fluid.
AB  - We have used a density-functional theory based on the interaction site model to
      predict the liquid-vapor coexistence curve of nitrogen fluid. The pressure and
      chemical potential were calculated from thermodynamic integrations. The different
      paths of thermodynamic integration provide slightly different predictions for the
      liquid-vapor coexistence curve. However, these critical points and coexistence
      curves evaluated by the theory are in qualitative agreement with the experimental
      data. The theoretical coexistence curves scaled to critical constants agree with
      the experimental data quantitatively.

PMID- 15260636
TI  - Potential energy surface for an electron transfer reaction mediated by a metal
      adlayer.
AB  - A model Hamiltonian for electron transfer from a metal electrode to a solvated
      reactant via a metallic adsorbate is proposed. The adsorbates are distributed
      randomly over the electrode surface, and a coherent-potential approximation has
      been employed to treat this randomness. Both the adsorbates and the reactant are
      assumed to interact with the solvent, which is modeled as a bath of phonons with
      frequencies in the classical regime. Both the adiabatic and the nonadiabatic
      potential energy surfaces are calculated, and their dependence on the adsorbate
      coverage is highlighted. In the low coverage regime the potential-energy surfaces
      exhibit features similar to a bridge-assisted electron transfer reaction, whereas
      for higher coverages the surfaces resemble those for direct heterogeneous
      transfer. This change of shape is caused by the metallization of the adsorbate
      layer at higher coverages.

PMID- 15260637
TI  - Optical anisotropy of nanotube suspensions.
AB  - A semimacroscopic model of an optically anisotropic nanotube suspension is
      derived perturbatively from Maxwell's equations in a dielectric medium. We
      calculate leading-order expressions, valid in the dilute and semidilute limits,
      for the intrinsic and form contributions to the complex dielectric tensor in
      terms of the volume fraction, mean orientation, aspect ratio, optical anisotropy,
      and optical contrast of the nanotubes. The birefringence and dichroism are
      derived explicitly to leading order in fluctuations, and the connection with
      depolarized light scattering is established. The results are generalized to
      include tube deformation.

PMID- 15260638
TI  - Theory of bulk, surface and interface phase transition kinetics in thin films.
AB  - We report a theoretical study of phase transition kinetics in confined two
      dimensional systems, motivated by recent experimental results on the amorphous-to
      crystalline transition in supported, thin amorphous water films [E.H.G. Backus,
      M.L. Grecea, A.W. Kleyn, and M. Bonn, Phys. Rev. Lett. (to be published)]. We
      generalize and extend existing theories to simultaneously describe the converted
      (crystalline) fractions in the bulk, at the sample-vacuum surface, and at the
      sample-support interface as a function of time. The general approach presented
      here results in expressions for the time-dependent converted bulk, surface, and
      interface fractions, for arbitrary desorption rate from the thin film, nucleation
      and growth rates and also includes finite nucleation grain size. The converted
      bulk, surface, and interface fractions are calculated for nucleation of the new
      phase occurring (i) in the bulk, (ii) at the support-sample interface, and (iii)
      at the sample surface (sample-vacuum interface), resulting in nine expressions.
      The results demonstrate the advantage of monitoring bulk, surface and interface
      fractions simultaneously to make definite statements regarding the location of
      the nucleation, and to reliably determine the values of the relevant
      crystallization parameters.

PMID- 15260639
TI  - Monte Carlo simulations of antibody adsorption and orientation on charged
      surfaces.
AB  - Monte Carlo simulations were performed to study the adsorption and orientation of
      antibodies on charged surfaces based on both colloidal and all-atom models. The
      colloidal model antibody consists of 12 connected beads representing the 12
      domains of an antibody molecule. The structure of the all-atom antibody model was
      taken from the protein databank. The effects of the surface charge sign and
      density, the solution pH and ionic strength on the adsorption and orientation of
      different colloidal model antibodies with different dipole moments were examined.
      Simulation results show that both the 12-bead and the all-atom models of the
      antibody, for which the dipole moment points from the Fc to (Fab)2 fragments,
      tend to have the desired "end-on" orientation on positively charged surfaces and
      undesired "head-on" orientation on negatively charged surfaces at high surface
      charge density and low solution ionic strength where electrostatic interactions
      dominate. At low surface charge density and high solution ionic strength where
      van der Waals interactions dominate, 12-bead model antibodies tend to have "lying
      flat" orientation on surfaces. The orientation of adsorbed antibodies results
      from the compromise between electrostatic and van der Waals interactions. The
      dipole moment of an antibody is an important factor for antibody orientation on
      charged surfaces when electrostatic interactions dominate. This charge-driven
      protein orientation hypothesis was verified by our simulations results in this
      work. It was further confirmed by surface plasmon resonance biosensor and time-of
      flight secondary ion mass spectrometry experiments reported elsewhere.

PMID- 15260640
TI  - Electromechanical actuation of composite material from carbon nanotubes and
      ionomeric polymer.
AB  - An actuating system composed of nafion ionomeric polymer coated with single
      walled carbon nanotubes electrodes was studied as an electromechanical actuator.
      The actuator gives a sizable mechanical response to low voltages (turn-on voltage
      of approximately 2.5 V) under open-air conditions, i.e., in the absence of a
      surrounding supporting electrolyte. The actuator is active under both dc and ac
      bias and has a strong resonance at low frequencies which is dependent upon the
      size of the actuator. The actuator was studied using Fourier transform infrared
      and vis-NIR spectroscopies, cyclic voltammetry, and by the current-time response
      under an applied step voltage. An analytical model is proposed to understand the
      electrical behavior, which is consistent with the spectroscopic results.

PMID- 15260641
TI  - Combining molecular dynamics and ab initio quantum-chemistry to describe electron
      transfer reactions in electrochemical environments.
AB  - A theoretical model is presented aimed to provide a detailed microscopic
      description of the electron transfer reaction in an electrochemical environment.
      The present approach is based on the well-known two state model extended by the
      novelty that the energy of the two states involved in the electron transfer
      reaction is computed quantum mechanically as a function of the solvent
      coordinate, as defined in the Marcus theory, and of the intensity of an external
      electric field. The solvent conformations defining the reaction coordinate are
      obtained from classical molecular dynamics and then transferred to the quantum
      mechanical model. The overall approach has been applied to the electron transfer
      between a chloride anion and a single crystal Cu(100) electrode. It is found that
      the solvent exerts a strong influence on the equilibrium geometry of the halide
      and hence on the relative energy of the two states involved in the electron
      transfer reaction. Finally, both solvent fluctuations and external field
      facilitate the electron transfer although solvent effects have a stronger
      influence.

PMID- 15260642
TI  - Charge transfer efficiency in hybrid bulk heterojunction composites.
AB  - On the basis of recently published electrochemical measurements, the charge
      transfer efficiency within CdSe nanocrystal/conducting polymer heterojunction
      composites was investigated by means of luminescence interaction strength. It was
      found that poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] and poly-9
      vinylcarbazole luminescence was not totally quenched by nanocrystals, whereas
      poly-3-octylthiophene and polyvinylpyrrolidone was completely quenched. In case
      of poly-3-hexylthiophene, the nanocrystal luminescence was quenched. The results
      are in complete agreement with the electrochemical findings and thus, the CdSe
      nanocrystal/Polyvinylpyrrolidone composite should be a promising material for
      electroluminescent devices.

PMID- 15260644
TI  - Internal structure of dendrimers in the melt under shear: a molecular dynamics
      study.
AB  - The molecular structure of fluids composed of dendrimers of different generations
      is studied using nonequilibrium molecular dynamics (NEMD). NEMD results for
      dendrimer melts undergoing planar Couette flow are reported and analyzed with
      particular attention paid to the shear-induced changes in the internal structure
      of dendrimers. The radii of gyration, pair distribution functions and the fractal
      dimensionality of the dendrimers are determined at different strain rates. The
      location of the terminal groups is analyzed and found to be uniformly distributed
      throughout the space occupied by the molecules. The fractal dimension as a
      function of strain rate displays crossover behavior analogous to the
      Newtonian/non-Newtonian transition of shear viscosity.

PMID- 15260643
TI  - Folding of the GB1 hairpin peptide from discrete path sampling.
AB  - The discrete path sampling technique is used to calculate folding pathways of the
      16-amino acid beta hairpin-forming sequence from residues 41-56 of the B1 domain
      of protein G. The folding time is obtained using master equation dynamics and
      kinetic Monte Carlo simulations, and the time evolution of different order
      parameters and occupation probabilities of groups of minima are calculated and
      used to characterize intermediates on the folding pathway.

PMID- 15260645
TI  - Simple growth models of rigid multifilament biopolymers.
AB  - The growth dynamics of rigid biopolymers, consisting of N parallel
      protofilaments, is investigated theoretically using simple approximate models. In
      our approach, the structure of a polymer's growing end and lateral interactions
      between protofilaments are explicitly taken into account, and it is argued that
      only few configurations are important for a biopolymer's growth. As a result,
      exact analytic expressions for growth velocity and dispersion are obtained for
      any number of protofilaments and arbitrary geometry of the growing end of the
      biopolymer. Our theoretical predictions are compared with a full description of
      biopolymer growth dynamics for the simplest N=2 model. It is found that the
      results from the approximate theory are approaching the exact ones for large
      lateral interactions between the protofilaments. Our theory is also applied to
      analyze the experimental data on the growth of microtubules.

PMID- 15260646
TI  - Nucleation in binary polymer blends: effects of foreign mesoscopic spherical
      particles.
AB  - We study nucleation in binary polymer blends in the presence of mesoscopic
      spherical particles using self-consistent field theory, considering both
      heterogeneous and homogeneous nucleation mechanisms. Heterogeneous nucleation is
      found to be highly sensitive to surface selectivity and particle size, with
      rather subtle dependence on the particle size. Particles that preferentially
      adsorb the nucleating species generally favor heterogeneous nucleation. For
      sufficiently strong adsorption, barrierless nucleation is possible. By comparing
      the free energy barrier for homogeneous and heterogeneous nucleation, we
      construct a kinetic phase diagram.

PMID- 15260647
TI  - Improved theoretical description of protein folding kinetics from rotations in
      the phase space of relevant order parameters.
AB  - A method is introduced to construct a better approximation for the reaction
      coordinate for protein folding from known order parameters. The folding of a two
      state off-lattice alpha helical Go-type protein is studied using molecular
      dynamics simulations. Folding times are computed directly from simulation, as
      well as theoretically using an equation derived by considering Brownian-type
      dynamics for the putative reaction coordinate. Theoretical estimates of the
      folding time using the number of native contacts (Qn) as a reaction coordinate
      were seen to differ quite significantly from the true folding time of the
      protein. By considering the properties of the bimodal free energy surface of this
      protein as a function of Qn and another relevant coordinate for folding Q (the
      total number of contacts), we show that by introducing a rotation in the phase
      space of the order parameters Q and Qn, we can construct a new reaction
      coordinate q that leads to a fivefold improvement in the estimate of the folding
      rate. This new coordinate q, resulting from the rotation, lies along the line
      connecting the unfolded and folded ensemble minima of the free energy map plotted
      as a function of the original order parameters Q and Qn. Possible reasons for the
      remaining discrepancy between the folding time computed theoretically and from
      folding simulations are discussed.

PMID- 15260648
TI  - The influence of polytypic structures on the M011-->M101 solid-solid phase
      transition of n-C36H74: an application of the oblique infrared transmission
      method.
AB  - The molecular displacements on the M011-->M101 phase transition of n
      hexatriacontane (n-C36H74) have been investigated with an IR microscope designed
      for the oblique infrared transmission method. It has been clarified that two
      polytypic structures of the M011 modification, single-layered structure (Mon) and
      double-layered one (Orth II), both transform to the M101 modification of single
      layered structure with their respective mechanisms. On the M011(Mon)-->M101
      transition, the inclination direction of molecular axis is changed by 90 degrees
      through an intermediate state in which the molecular chain is set perpendicular
      to the basal plane of the single crystal. On the other hand, a polymorphic
      polytypic composite structural change on the M011(Orth II)-->M101 transition is
      accomplished through two kinds of molecular displacements occurring alternately
      along the stacking direction of molecular layers.

PMID- 15260649
TI  - Chain elongation suppression of cyclic block copolymers in lamellar microphase
      separated bulk.
AB  - Chain elongation suppression of cyclic block copolymers in microphase-separated
      bulk was determined quantitatively. Solvent-cast and annealed films are confirmed
      to show alternating lamellar structure and their microdomain spacing D increases
      with increasing total molecular weight M according to the relationship D
      proportional, variant M0.59, which agrees quite consistently with the
      theoretically predicted power law, i.e., D proportional, variant M3/5. This
      result is in contrast to the well-established issue for linear block copolymers,
      where the relationship D proportional, variant M2/3 has been confirmed to hold
      both experimentally and theoretically. This means that chain elongation of each
      component block is suppressed considerably, owing to their looped conformation in
      strongly segregated bulk.

PMID- 15260650
TI  - Conformation studies on sol-gel transition in triblock copolymer solutions.
AB  - The gelation of physically associating triblock copolymers in a good solvent was
      investigated by means of the Monte Carlo simulation and a gelation process based
      on the conformation transition of the copolymer that was described in detail. In
      our simulative system, it has been found that the gelation is closely related
      with chain conformations, and there exist four types of chains defined as free,
      dangling, loop, and bridge conformations. The copolymer chains with different
      conformations contribute to the formation of gel in different ways. We proposed a
      conformational transition model, by which we evaluated the role of these four
      types of chains in sol-gel transition. It was concluded that the free chains
      keeping the conformation transition equilibrium and the dangling conformation
      being the hinge of conformation transition, while the chain with loop
      conformation enlarges the size of the congeries and the chain with bridge
      conformations binds the congeries consisted of the copolymer chains. In addition,
      the effects of temperature and concentration on the physical gelation, the
      association of the copolymer congeries, and the copolymer chain conformations'
      distribution were discussed. Furthermore, we employed the structure factor
      analysis to study the association of copolymer conformations and long-range order
      of the simulation system and found our results are in agreement with the previous
      experimental conclusions.

PMID- 15260651
TI  - Percolation-to-droplets transition during spinodal decomposition in polymer
      blends, morphology analysis.
AB  - Phase separation kinetics of the off-critical mixture of polystyrene and
      poly(methylphenylsiloxane) is studied by the time-resolved light scattering and
      optical microscopy. The results from the light scattering experiments are
      correlated with the images obtained by the optical microscopic observation in
      order to find characteristic features of the scattering intensity during the
      percolation-to-droplets morphology transition. At the beginning of the spinodal
      decomposition process only a bicontinuous network is present in the system and
      the light scattering intensity has only one peak. The network coarsens and at the
      same time small droplets appear in the system resulting in a growth of the
      scattering intensity at very small wave vectors. When the large network starts to
      break up into disjoint elongated domains a second peak in the scattering
      intensity appears. Finally, both peaks merge into a single peak at zero wave
      vector, indicating a complete transformation of elongated domains into spherical
      droplets of variable sizes. The comparison of the direct microscopic observations
      with the light scattering spectra shows that the process of breaking up of the
      bicontinuous network starts when the growth of the first peak, corresponding to
      the bicontinuous pattern, becomes very slow (essentially pinned down).

PMID- 15260652
TI  - Preferential hydration and the exclusion of cosolvents from protein surfaces.
AB  - Protein stability is enhanced by the addition of osmolytes, such as sugars and
      polyols and inert crowders, such as polyethylene glycols. This stability
      enhancement has been quantified by the preferential hydration parameter which can
      be determined by experiments. To understand the mechanism of protein stability
      enhancement, we present a statistical mechanical analysis of the preferential
      hydration parameter based upon Kirkwood-Buff theory. Previously, the preferential
      hydration parameter was interpreted in terms of the number of hydration waters,
      as well as the cosolvent exclusion volume. It was not clear how accurate these
      interpretations were, nor what the relationship is between the two. By using the
      Kirkwood-Buff theory and experimental data, we conclude that the contribution
      from the cosolvent exclusion dominantly determines the preferential hydration
      parameters for crowders. For osmolytes, although the cosolvent exclusion largely
      determines the preferential hydration parameters, the contribution from hydration
      may not be negligible.

PMID- 15260653
TI  - Distribution functions for filaments under tension.
AB  - We develop a biased Monte Carlo simulation technique to measure the distribution
      functions of the extension and the end-to-end distance of fluctuating filaments
      stretched by external force. The method is applicable for arbitrary ratio of the
      persistence length to the contour length and for arbitrary forces, and also for
      the case of steric constraints, such as an external wall. The fundamental idea
      underlying the algorithm is to account explicitly for the length-scale dependence
      of the effective elastic moduli. We find that orientational fluctuations and wall
      effects produce non-Gaussian distributions for nearly rigid filaments in the
      small to intermediate force regime. The simulation results are tested against
      analytic expressions for the force-extension curves, both in the semiflexible and
      nearly stiff limits.

PMID- 15260654
TI  - Tracing the phase diagram of the four-site water potential (TIP4P).
AB  - We present here the phase diagram for one of the most popular water models, the
      four-point transferable intermolecular potential (TIP4P) model. We show that
      TIP4P model, does indeed provide a qualitatively correct description of the phase
      diagram of water. The melting line of the five-point transferable intermolecular
      potential (TIP5P) at low pressures is also presented.

PMID- 15260655
TI  - Comment on "The incomplete beta function law for parallel tempering sampling of
      classical canonical systems" [J. Chem. Phys. 120, 4119 (2004)].
AB  - We explain the apparent discrepancy between the analysis of the indicated article
      and that of earlier work cited by it, and present an asymptotic formula that
      encompasses limiting behaviors described in both. (c) 2004 American Institute of
      Physics.

PMID- 15260657
TI  - Kinetic isotope effect in hydrogen transfer arising from the effects of
      rotational excitation and occurrence of hydrogen tunneling in molecular systems.
AB  - Hydrogen kinetic isotope effect with values of alpha identical with
      ln(kH/kT)/ln(kD/kT)>3.3 which are generally ascribed to quantum tunneling of
      hydrogen are shown to arise in O+HCl(DCl,TCl) reactions due to the effects of
      rotational excitation on the distribution of encounters with the critical
      dividing surface. At higher rotational excitations these distributions are
      shifted towards the regions of the critical dividing surface with low barrier
      energies which can lead to a large enhancement of the barrier crossing. This
      effect depends strongly on the hydrogen isotope involved in the reaction and, at
      some temperatures, gives rise to alpha much larger than 3.3. It can be readily
      seen that the effect should arise also in condensed molecular systems, due to
      internal rotations or other vibrations "perpendicular" to the reaction
      coordinate.

PMID- 15260658
TI  - Plane wave packet formulation of atom-plus-diatom quantum reactive scattering.
AB  - We recently interpreted several reactive scattering experiments using a plane
      wave packet (PWP) formulation of quantum scattering theory [see, e.g., S. C.
      Althorpe, F. Fernandez-Alonso, B. D. Bean, J. D. Ayers, A. E. Pomerantz, R. N.
      Zare, and E. Wrede, Nature (London) 416, 67 (2002)]. This paper presents the
      first derivation of this formulation for atom-plus-diatom reactive scattering,
      and explains its relation to conventional time-independent reactive scattering.
      We generalize recent results for spherical-particle scattering [S. C. Althorpe,
      Phys. Rev. A 69, 042702 (2004)] to atom-rigid-rotor scattering in the space-fixed
      frame, atom-rigid-rotor scattering in the body-fixed frame, and finally A+BC
      rearrangement scattering. The reactive scattering is initiated by a plane wave
      packet, describing the A+BC reagents in center-of-mass scattering coordinates,
      and is detected by projecting onto a series of AC+B (or AB+C) plane wave "probe"
      packets. The plane wave packets are localized at the closest distance from the
      scattering center at which the interaction potential can be neglected. The time
      evolution of the initial plane wave packet provides a clear visualization of the
      scattering into space of the reaction products. The projection onto the probe
      packets yields the time-independent, state-to-state scattering amplitude, and
      hence the differential cross section. We explain how best to implement the PWP
      approach in a numerical computation, and illustrate this with a detailed
      application to the H+D2 reaction.

PMID- 15260659
TI  - Efficient hybrid density functional calculations in solids: assessment of the
      Heyd-Scuseria-Ernzerhof screened Coulomb hybrid functional.
AB  - The present work introduces an efficient screening technique to take advantage of
      the fast spatial decay of the short range Hartree-Fock (HF) exchange used in the
      Heyd-Scuseria-Ernzerhof (HSE) screened Coulomb hybrid density functional. The
      screened HF exchange decay properties and screening efficiency are compared with
      traditional hybrid functional calculations on solids. The HSE functional is then
      assessed using 21 metallic, semiconducting, and insulating solids. The examined
      properties include lattice constants, bulk moduli, and band gaps. The results
      obtained with HSE exhibit significantly smaller errors than pure density
      functional theory (DFT) calculations. For structural properties, the errors
      produced by HSE are up to 50% smaller than the errors of the local density
      approximation, PBE, and TPSS functionals used for comparison. When predicting
      band gaps of semiconductors, we found smaller errors with HSE, resulting in a
      mean absolute error of 0.2 eV (1.3 eV error for all pure DFT functionals). In
      addition, we present timing results which show the computational time
      requirements of HSE to be only a factor of 2-4 higher than pure DFT functionals.
      These results make HSE an attractive choice for calculations of all types of
      solids.

PMID- 15260660
TI  - Mapping potential energy surfaces.
AB  - A recently proposed dynamical method [A. Laio and M. Parrinello, Proc. Natl.
      Acad. Sci. U.S.A. 99, 12562 (2002)] allows us to globally sample the free energy
      surface. This approach uses a coarse-grained non-Markovian dynamics to bias
      microscopic atomic trajectories. After a sufficiently long simulation time, the
      global free energy surface can be reconstructed from the non-Markovian dynamics.
      Here we apply this scheme to study the T=0 free energy surface, i.e., the
      potential energy surface in coarse-grained space. We show that the accuracy of
      the reconstructed potential energy surface can be dramatically improved by a
      simple postprocessing procedure with only minor computational overhead. We
      illustrate this approach by conducting conformational analysis on a small organic
      molecule, demonstrating its superiority over traditional unbiased approaches in
      sampling potential energy surfaces in coarse-grained space.

PMID- 15260661
TI  - Perturbation theory corrections to the two-particle reduced density matrix
      variational method.
AB  - In the variational 2-particle-reduced-density-matrix (2-RDM) method, the ground
      state energy is minimized with respect to the 2-particle reduced density matrix,
      constrained by N-representability conditions. Consider the N-electron Hamiltonian
      H(lambda) as a function of the parameter lambda where we recover the Fock
      Hamiltonian at lambda=0 and we recover the fully correlated Hamiltonian at
      lambda=1. We explore using the accuracy of perturbation theory at small lambda to
      correct the 2-RDM variational energies at lambda=1 where the Hamiltonian
      represents correlated atoms and molecules. A key assumption in the correction is
      that the 2-RDM method will capture a fairly constant percentage of the
      correlation energy for lambda in (0,1] because the nonperturbative 2-RDM approach
      depends more significantly upon the nature rather than the strength of the two
      body Hamiltonian interaction. For a variety of molecules we observe that this
      correction improves the 2-RDM energies in the equilibrium bonding region, while
      the 2-RDM energies at stretched or nearly dissociated geometries, already highly
      accurate, are not significantly changed. At equilibrium geometries the corrected
      2-RDM energies are similar in accuracy to those from coupled-cluster singles and
      doubles (CCSD), but at nonequilibrium geometries the 2-RDM energies are often
      dramatically more accurate as shown in the bond stretching and dissociation data
      for water and nitrogen.

PMID- 15260662
TI  - Singular value decomposition applied to the compression of T3 amplitude for the
      coupled cluster method.
AB  - We apply the singular value decomposition to compress the degrees of freedom of
      T3 amplitude for the CCSDT-1 method (compressed CCSDT-1). This method enables us
      to make the number of the T3 amplitudes less than that of the T2 amplitudes,
      making CCSDT-1 calculations much less expensive without losing accuracy. We
      perform test calculations on some atoms and molecules to investigate the
      applicability of this method. Computational results for the electronic energies
      as well as timings of these calculations are presented.

PMID- 15260663
TI  - Second-order Moller-Plesset theory with linear R12 terms (MP2-R12) revisited:
      auxiliary basis set method and massively parallel implementation.
AB  - Ab initio electronic structure approaches in which electron correlation
      explicitly appears have been the subject of much recent interest. Because these
      methods accelerate the rate of convergence of the energy and properties with
      respect to the size of the one-particle basis set, they promise to make
      accuracies of better than 1 kcal/mol computationally feasible for larger chemical
      systems than can be treated at present with such accuracy. The linear R12 methods
      of Kutzelnigg and co-workers are currently the most practical means to include
      explicit electron correlation. However, the application of such methods to
      systems of chemical interest faces severe challenges, most importantly, the still
      steep computational cost of such methods. Here we describe an implementation of
      the second-order Moller-Plesset method with terms linear in the interelectronic
      distances (MP2-R12) which has a reduced computational cost due to the use of two
      basis sets. The use of two basis sets in MP2-R12 theory was first investigated
      recently by Klopper and Samson and is known as the auxiliary basis set (ABS)
      approach. One of the basis sets is used to describe the orbitals and another, the
      auxiliary basis set, is used for approximating matrix elements occurring in the
      exact MP2-R12 theory. We further extend the applicability of the approach by
      parallelizing all steps of the integral-direct MP2-R12 energy algorithm. We
      discuss several variants of the MP2-R12 method in the context of parallel
      execution and demonstrate that our implementation runs efficiently on a variety
      of distributed memory machines. Results of preliminary applications indicate that
      the two-basis (ABS) MP2-R12 approach cannot be used safely when small basis sets
      (such as augmented double- and triple-zeta correlation consistent basis sets) are
      utilized in the orbital expansion. Our results suggest that basis set
      reoptimization or further modifications of the explicitly correlated ansatz
      and/or standard approximations for matrix elements are necessary in order to make
      the MP2-R12 method sufficiently accurate when small orbital basis sets are used.
      The computer code is a part of the latest public release of Sandia's Massively
      Parallel Quantum Chemistry program available under GNU General Public License.

PMID- 15260664
TI  - Continuum equations for magnetic and dielectric fluids with internal rotations.
AB  - Several authors have attempted with varying success to derive a complete set of
      basic equations for the motion of polar fluids having internal rotations and
      hence in a state of polarization disequilibrium. This work develops a complete
      set of governing equations derived on the basis of dynamic balance relationships
      with the dissipation function determined from thermodynamic consideration. The
      magnetization relaxation equation is thereby determined from requirement of
      positive entropy production along with a complete set of constitutive laws
      including antisymmetric terms of the total stress tensor. The analysis employs
      the Minkowski expression of electromagnetic momentum and assumes that the product
      of electromagnetic stress and velocity contributes to the energy balance on the
      same footing as contact stresses of pressure and viscous origin. The work refines
      the treatment of our earlier effort carrying out the analysis to first order in
      the ratio of fluid velocity to light speed throughout.

PMID- 15260665
TI  - A diagrammatic formulation of the kinetic theory of fluctuations in equilibrium
      classical fluids. IV. The short time behavior of the memory function.
AB  - Using a recently developed diagrammatic formulation of the kinetic theory of
      fluctuations in liquids, we investigate the short time behavior of the memory
      function for density fluctuations in a classical atomic fluid. At short times,
      the memory function has a large contribution that is generated by the repulsive
      part of the interatomic potential. We introduce a small parameter that is a
      measure of the softness of the repulsive part of the potential. The diagrams in
      the memory function that contribute to lowest order in that small parameter are
      identified and summed to give an explicit expression for the dominant
      contribution to the memory function at short times. The result leads to a theory
      for fluids with continuous potentials that is similar to the Enskog theory for
      hard sphere fluids.

PMID- 15260666
TI  - Perturbational relativistic theory of electron spin resonance g-tensor.
AB  - We carry out a complete treatment of the leading-order relativistic one-electron
      contributions, arising from the Breit-Pauli Hamiltonian, to the g-tensor of
      electron spin resonance spectroscopy. We classify the different terms and discuss
      their interpretation as well as give numerical ab initio estimates for the F2(-),
      Cl2(-), Br2(-), and I2(-) series, using analytical response theory calculations
      with a multiconfigurational self-consistent field reference state. The results
      are compared to available experimental data. (c) 2004 American Institute of
      Physics

PMID- 15260667
TI  - LocalSCF method for semiempirical quantum-chemical calculation of ultralarge
      biomolecules.
AB  - A linear-scaling semiempirical method, LocalSCF, has been proposed for the
      quantum-chemical calculations of ultralarge molecular systems by treating the
      large-scale molecular task as a variational problem. The method resolves the self
      consistent field task through the finite atomic expansion of weakly nonorthogonal
      localized molecular orbitals. The inverse overlap matrix arising from the
      nonorthogonality of the localized orbitals is approximated by preserving the
      first-order perturbation term and applying the second-order correction by means
      of a penalty function. This allows for the separation of the orbital expansion
      procedure from the self-consistent field optimization of linear coefficients,
      thereby maintaining the localized molecular orbital size unchanged during the
      refinement of linear coefficients. Orbital normalization is preserved
      analytically by the variation of virtual degrees of freedom, which are orthogonal
      to the initial orbitals. Optimization of linear coefficients of localized
      orbitals is performed by a gradient procedure. The computer program running on a
      commodity personal computer was applied to the GroEL-GroES chaperonin complex
      containing 119,273 atoms.

PMID- 15260668
TI  - Six-dimensional vibrational analysis of coupled intermolecular vibrations in a
      binary cluster.
AB  - We report on full- (six-) dimensional calculations of the intermolecular
      vibrations of a binary aromatic-solvent cluster. An exact Hamiltonian for this
      kind of interaction is modified in a general manner in order to perform
      calculations of molecules without symmetry. The binary cluster phenol(H2O)1 is
      used as a test case since its intermolecular vibrations are anharmonic and highly
      coupled. The formulation of the Schrodinger equation leads to a complex-valued
      eigenvalue problem with a dimension larger than two million, which is solved by
      filter diagonalization to obtain both eigenvalues and eigenvectors. With the
      knowledge of the eigenvectors, an interpretation of all eigenvalues is possible
      by a characterization with pseudoquantum numbers that are related to the widely
      used nomenclature of intermolecular normal motions in aromatic(solvent) clusters.

PMID- 15260669
TI  - Absolute intensities of Raman trace scattering from bicyclo-[1.1.1]-pentane.
AB  - Our previous theoretical studies have identified the Raman intensity parameter
      for the bridgehead C-H stretch in bicyclo-[1.1.1]-pentane as the largest for any
      saturated hydrocarbon yet considered, while the methylene C-H parameter is
      predicted to be ordinary. Theoretical methods including self-consistent field,
      static and time dependent density functional theory, and coupled cluster, all
      predict a large bridgehead intensity parameter, but differ widely in the actual
      value. We have synthesized bicyclo-[1.1.1]-pentane and recorded the absolute
      intensity Raman trace scattering spectra. The recorded intensity of a resonance
      polyad in the C-H stretching region has been resolved and distributed onto the
      fundamental modes through an anharmonic resonance analysis from a computed
      quartic force field. The experimental internal coordinate intensity parameters
      have been obtained and compared with those computed. Although the static and
      dynamic density functional values overestimate the parameter by 10%-18%, the
      values predicted at the coupled-cluster level are found to be correct to within
      experimental error.

PMID- 15260670
TI  - Reactions of C(1D) with H2 and its deuterated isotopomers, a wave packet study.
AB  - Using a Chebyshev wave packet method, total and state-resolved reaction
      probabilities (J=0) were calculated for the reactions of C(1D) with various
      hydrogen isotopomers (H2, D2, and HD, nu i=0, j i=0) on a recent ab initio
      potential energy surface. For all the isotopic variants, it was found that the
      initial state specified reaction probabilities have no energy threshold and are
      strongly oscillatory, indicative of the involvement of long-lived resonances in
      this barrierless reaction. The J=0 product vibrational and rotational
      distributions for all three isotopic reactions, and the CH/CD branching ratio for
      the C+HD reaction, show strong dependence on the collision energy, further
      underscoring the important role played by the resonances. The generally decaying
      vibrational distributions and highly excited rotational distributions, which
      corroborate an insertion mechanism, and the dominance of the CD+H channel in the
      C+HD reaction are consistent with existing experimental observations. Initial
      state specified integral cross sections and rate constants were estimated using a
      capture model. The estimated rate constants were found to be close and in the
      order kHD>kH2>kD2. Finally, a method to calculate branching ratio in the C+HD
      reaction is proposed.

PMID- 15260671
TI  - Photodissociation of HCl and small (HCl)m complexes in and on large Ar n
      clusters.
AB  - Photodissociation experiments were carried out at 193 nm for single HCl molecules
      which are adsorbed on the surface of large Ar n clusters and small (HCl)m
      complexes which are embedded in the interior of these clusters. For the surface
      case the size dependence is measured for the average sizes n=140-1000. No cage
      exit events are observed in agreement with the substitutional position of the
      molecule deeply buried in the outermost shell. This result is confirmed by a
      molecular dynamics simulation of the pickup process under realistic conditions
      concerning the experiment and the interaction potentials. The calculations of the
      dissociation process employ the surface hopping model. For the embedded case the
      average sizes covered are m=3 and 6 and n=8-248. The kinetic energy of the H atom
      fragments is measured exhibiting peaks at zero and around 2.0 eV which mark
      completely caged and unperturbed fragments, respectively. The ratio of theses
      peaks strongly depends on the cluster size and agrees well with theoretical
      predictions for one and two closed icosahedral shells, in which the nonadiabatic
      coupling of all states was accounted for.

PMID- 15260672
TI  - Electron attachment on HI and DI in a uniform supersonic flow: thermalization of
      the electrons.
AB  - In order to check the electron thermalization in the CRESU technique (Cinetique
      de Reaction en Ecoulement Supersonique Uniforme, e.g., "reaction kinetics in a
      uniform supersonic flow"), electron attachment on HI and DI has been studied in
      the 48-170 K range. Attachment to HI is exothermic and the reaction is expected
      to be fast and to proceed at a rate close to the capture limit. On the contrary,
      attachment to DI is slightly endothermic, and a strong positive temperature
      dependence of the measured rate coefficient is expected if the electrons are
      thermal. This dependence is not observed, and we conclude that the electrons are
      not in thermal equilibrium with the neutrals in the afterglow. A model, based on
      electron heating by superelastic collisions with the buffer gas, is proposed to
      explain this fact and implications for previously published results are
      discussed.

PMID- 15260673
TI  - Infrared-infrared double resonance spectroscopy of cyanoacetylene in helium
      nanodroplets.
AB  - Infrared-infrared double resonance spectroscopy is used as a probe of the
      vibrational dynamics of cyanoacetylene in helium droplets. The nu1 C-H stretching
      vibration of cyanoacetylene is excited by an infrared laser and subsequent
      vibrational relaxation results in the evaporation of approximately 660 helium
      atoms from the droplet. A second probe laser is then used to excite the same C-H
      stretching vibration downstream of the pump, corresponding to a time delay of
      approximately 175 micros. The hole burned by the pump laser is narrower than the
      single resonance spectrum, owing to the fact that the latter is inhomogeneously
      broadened by the droplet size distribution. The line width of the hole is
      characteristic of another broadening source that depends strongly on droplet
      size.

PMID- 15260674
TI  - Theoretical analysis of singlet and triplet excited states of nickel porphyrins.
AB  - Local density and generalized gradient approximation time-dependent density
      functional methods have been used for calculation of the singlet and triplet
      excited states of nickel-porphine, Ni-tetraphenyloporphine, and Ni
      octaethyloporphyrine. Special attention is paid to metal-ligand transitions and d
      d transitions. It is shown that the lowest exited singlet states of the three
      compounds can be described as a transfer of an electron from the porphine ring to
      the d(x2-y2) orbital of the nickel atom. On the other hand, the lowest excited
      triplet state arises from promotion of an electron between two nickel d orbitals,
      an occupied d(z2) and an empty d(x2-y2). It is proposed that a rapid quenching of
      the excited singlet states is due to an ultrafast intersystem crossing between
      1Eg)and 3Eg or 3B1g states.

PMID- 15260675
TI  - New ab initio potential energy surface for the (HOCO+-He) van der Waals complex.
AB  - A three-dimensional potential energy surface has been calculated for the ground
      electronic state of the HOCO+-He system. The calculations were performed at the
      coupled electron pair approximation level with an extended basis set which
      ensures a balance between accuracy and feasability. The validity of the method
      and of the basis set was tested through calculations of the polarizability of the
      He atom and of the spectroscopic constants of the HOCO+ ion. The calculated
      potential energy surface has been fitted to a spherical harmonic expansion to
      facilitate calculations of rotational excitation of HOCO+ by collisions with He.

PMID- 15260676
TI  - Rotational isomerism of acetic acid isolated in rare-gas matrices: Effect of
      medium and isotopic substitution on IR-induced isomerization quantum yield and
      cis-->trans tunneling rate.
AB  - Rotational isomerization of acetic acid (CH3COOH) is studied in Ar, Kr, and Xe
      matrices. The light-induced trans-->cis reaction is promoted using resonant
      excitation of a number of modes in the 3500-7000 cm(-1) region, and the quantum
      yields for this process are measured for various acetic acid isotopologues and
      matrix materials. For excitation of acetic acid at energies above the predicted
      isomerization energy barrier (> or =4400 cm(-1)), the measured quantum yields are
      in average 2%-3%, and this is one order of magnitude smaller than the
      corresponding values known for formic acid (HCOOH). This difference is
      interpreted in terms of the presence of the methyl group in acetic acid, which
      enhances energy relaxation channels competing with the rotational isomerization.
      This picture is supported by the observed large effect of deuteration of the
      methyl group on the photoisomerization quantum yield. The trans-->cis reaction
      quantum yields are found to be similar for Ar, Kr, and Xe matrices, suggesting
      similar energy relaxation processes for this molecule in the various matrices.
      The IR-induced cis-->trans process, studied for acetic acid deuterated in the
      hydroxyl group, shows reliably larger quantum yields as compared with the trans-
      >cis process. For pumping of acetic acid at energies below the predicted
      isomerization barrier, the trans-->cis reaction quantum yields decrease strongly
      when the photon energy decreases, and tunneling is the most probable mechanism
      for this process. For the cis-->trans dark reaction, the observed temperature and
      medium effects indicate the participation of the lattice phonons in the tunneling
      induced process.

PMID- 15260677
TI  - Molecular beam scattering of NO+Ne: a joint theoretical and experimental study.
AB  - The collision dynamics of the NO+Ne system is investigated in a molecular beam
      scattering experiment at a collision energy of 1055 cm(-1). Employing resonance
      enhanced multiphoton ionization of NO, we measured state-resolved integral and
      differential cross sections for the excitation to various levels of both spin
      orbit manifolds. The dependence of the scattered intensity on the laser
      polarization is used to extract differential quadrupole moments for the collision
      induced angular momentum alignment. The set of cross section data is compared
      with results of a full quantum mechanical close coupling calculation using the
      set of ab initio potential energy surfaces of Alexander et al. [J. Chem. Phys.
      114, 5588 (2001)]. In previous work, it was found that the positions and
      rotational substructures for the lowest bend-stretch vibrational states derived
      from these surfaces agree very well with the observed spectrum of the NO-Ne
      complex. For the same potential, we find that the calculated cross sections show
      a less satisfactory agreement with the experimental data. While the overall Jf
      dependence and magnitude of the integral and differential cross sections are in
      good agreement, noticeable discrepancies exist for the angle dependence of the
      differential cross sections. In general, the calculated rotational rainbow
      structures are shifted towards larger scattering angles indicating that the
      anisotropy of the potential is overestimated in the fit to the ab initio points
      or in the ab initio calculation itself. For most states, we find the measured
      alignment moments to be in excellent agreement with the results of the
      calculation as well as with predictions of sudden models. Significant deviations
      from the sudden models are observed only for those fine-structure changing
      collisions which are dominated by forward scattering. Results of the full quantum
      calculation confirm the deviations for these states.

PMID- 15260678
TI  - Electron-impact ionization of CCl4 and CCl2F2.
AB  - Absolute partial and total cross sections for electron-impact ionization of CCl4
      and CCl2F2 are reported for electron energies from threshold to 1000 eV. The
      product ions are mass analyzed using a time-of-flight mass spectrometer and
      detected with a position-sensitive detector whose output demonstrates that all
      product ion species are collected with equal efficiency irrespective of their
      initial kinetic energies. Data are presented for production of CCl3(+), CCl2(+),
      CCl+, C+, Cl2(+), and CCl3(2+) from CCl4; and for production of CCl(2)F+,
      CClF2(+), CClF(+), (CCl+ + CF2(+)), Cl+, CF+, F+, and C+ from CCl2F2. Data are
      also reported for formation of (CCl2(+),Cl+) and (CCl+, Cl+) ion pairs from CCl4.
      The total cross section for each target is obtained as the sum of the partial
      cross sections. The overall uncertainty in the absolute cross sections for most
      of the singly charged ions is +/- 5-7 %. The present partial cross sections for
      lighter fragment ions are found to be considerably greater than had been
      previously reported but the most recent total cross section measurements agree
      well with those reported here. Neither the binary-encounter-Bethe theory nor the
      Deutsch-Mark theory reproduces the experimental cross sections correctly for both
      targets.

PMID- 15260679
TI  - Quantum Monte Carlo study of the reaction: Cl+CH3OH-->CH2OH+HCl.
AB  - A theoretical study is reported of the Cl+CH3OH-->CH2OH+HCl reaction based on the
      diffusion Monte Carlo (DMC) variant of the quantum Monte Carlo method. Using a
      DMC trial function constructed as a product of Hartree-Fock and correlation
      functions, we have computed the barrier height, heat of reaction, atomization
      energies, and heats of formation of reagents and products. The DMC heat of
      reaction, atomization energies, and heats of formation are found to agree with
      experiment to within the error bounds of computation and experiment. Moller
      Plesset second order perturbation theory (MP2) and density functional theory, the
      latter in the B3LYP generalized gradient approximation, are found to overestimate
      the experimental heat of reaction. Intrinsic reaction coordinate calculations at
      the MP2 level of theory demonstrate that the reaction is predominantly direct,
      i.e., proceeds without formation of intermediates, which is consistent with a
      recent molecular beam experiment. The reaction barrier as determined from MP2
      calculations is found to be 2.24 kcal/mol and by DMC it is computed to be
      2.39(49) kcal/mol.

PMID- 15260680
TI  - Complete quantum control of the population transfer branching ratio between two
      degenerate target states.
AB  - A five-level four-pulse phase-sensitive extended stimulated Raman adiabatic
      passage scheme is proposed to realize complete control of the population transfer
      branching ratio between two degenerate target states. The control is achieved via
      a three-node null eigenstate that can be correlated with an arbitrary
      superposition of the target states. Our results suggest that complete suppression
      of the yield of one of two degenerate product states, and therefore absolute
      selectivity in photochemistry, is achievable and predictable, even without
      studying the properties of the unwanted product state beforehand.

PMID- 15260681
TI  - Rotational energy transfer in NO (A 2Sigma+,v'=0) by N2 and O2 at room
      temperature.
AB  - State-to-state rotational energy transfer (RET) rate coefficients for NO (A
      2Sigma+, v'=0, J=5.5, 11.5, 17.5) were measured for N2 and O2 at room temperature
      using a pump-probe method. The NO A 2Sigma+ state is prepared by 226 nm light and
      the RET is monitored by fluorescence from the D 2Sigma+ v'=0 state, following
      excitation by a time-delayed laser at approximately 1.1 microm. Additionally,
      total collisional removal and final state distributions were measured exciting in
      the Q1+P21 band head, to simulate an NO laser-induced fluorescence atmospheric
      monitoring scheme. Time-resolved modeling is used to understand relaxation
      mechanisms and predict relaxation times in ambient air. H2O at atmospherically
      relevant concentrations does not affect the degree of RET in ambient air.

PMID- 15260682
TI  - Ab initio vibrational state calculations with a quartic force field: applications
      to H2CO, C2H4, CH3OH, CH3CCH, and C6H6.
AB  - For polyatomic molecules, n-mode coupling representations of the quartic force
      field (nMR-QFF) are presented, which include terms up to n normal coordinate
      couplings in a fourth-order polynomial potential energy function. The
      computational scheme to evaluate third-and fourth-order derivatives by finite
      differentiations of the energy is fully described. The code to generate the nMR
      QFF has been implemented into GAMESS program package and interfaced with the
      vibrational self-consistent field (VSCF) and correlation corrected VSCF (cc-VSCF)
      methods. As a demonstration, fundamental frequencies have been calculated by the
      cc-VSCF method based on 2MR-QFF for formaldehyde, ethylene, methanol, propyne,
      and benzene. The applications show that 2MR-QFF is a highly accurate potential
      energy function, with errors of 1.0-1.9% relative to the experimental value in
      fundamental frequencies. This approach will help quantitative evaluations of
      vibrational energies of a general molecule with a reasonable computational cost.

PMID- 15260683
TI  - The chlorobenzene-argon ground state intermolecular potential energy surface.
AB  - Using the coupled cluster singles and doubles including connected triple
      excitations model with the augmented correlation consistent polarized valence
      double zeta basis set extended with a set of 3s3p2d1f1g midbond functions, we
      evaluate the ground state intermolecular potential energy surface of the
      chlorobenzene-argon van der Waals complex. The minima of 420 cm(-1) are
      characterized by Ar atom position vectors of the length 3.583 A, forming an angle
      of 9.87 degrees with respect to the axis perpendicular to the chlorobenzene
      plane. These results are compared to those obtained for similar complexes and to
      the experimental data available. From the potential the three-dimensional
      vibrational eigenfunctions and eigenvalues are calculated and the results allow
      to correct and complete the experimental assignment.

PMID- 15260684
TI  - Observation and analysis of the 2g(1D) ion-pair state of I2: the g/u mixing
      between the 1u(1D) and 2g(1D) states.
AB  - We report the analysis of the 2g(1D) ion-pair state of I2 by perturbation
      facilitated optical-optical double resonance. The present study began with the
      observation of the 2g(1D)-A' 3Pi(2u) emission at around 230 nm during the
      analysis of the ultraviolet emissions originating form the 1u(1D) ion-pair state.
      The identification of this new transition helped us to specify the wavelengths
      for detecting the 2g(1D) state by emission, and also to estimate its absolute
      position. The intermediate states used to observe the 2g(1D) state were the B
      3Pi(0u(+))-b' 2u mixed states by the hyperfine interaction, which allowed us to
      combine the X 1Sigmag(+) ground state with the 2g(1D) state in the (1+1) photon
      excitation following the optical selection rules for one-photon transitions:
      2g(1D)<--b' 2u-B 3Pi(0u(+))<--X 1Sigmag(+). Our analysis covered the 2g(1D) state
      in the 0< or =v< or =12 and 9< or =J< or =40 ranges. The molecular constants and
      Rydberg-Klein-Rees (RKR) potential of the 2g(1D) state were reported. We
      discussed the occurrence of the 2g(1D)-A' 3Pi(2u) emission, when exciting to the
      1u(1D) v=0 state, and attributed it to the g/u mixing between the 2g(1D) and
      1u(1D) states by the hyperfine interaction. The effect of the perturbation on
      measured line intensities and lifetimes was evident.

PMID- 15260685
TI  - Phosphorus hyperfine structure in the electronic spectrum of the HPCl free
      radical.
AB  - The 444 nm 2 0 (1) bands of the A 2A'-X 2A" transition of the jet-cooled HP 35Cl
      and HP 37Cl radicals have been studied at high resolution using the pulsed
      electric discharge technique with a precursor mixture of PCl3 and H2. Spectra
      recorded with linewidths of approximately 360 MHz revealed resolved hyperfine
      structure in both isotopomers arising from the excited state Fermi contact
      interaction of the unpaired electron with the magnetic moment of the 31P nucleus,
      with aF'=0.0641(10) cm(-1) and 0.0636(31) cm(-1) for HP 35Cl and HP 37Cl,
      respectively. No contribution from the ground state, or excited state
      contributions from the hydrogen or chlorine nuclei were resolved, confirming ab
      initio predictions that HPCl is a p pi radical in the X state, and an s sigma
      radical with a substantial contribution from the phosphorus 3s atomic orbital in
      the A state. The free atom comparison method has been used to estimate that the
      singly occupied molecular orbital in the excited state has 14% phosphorus 3s
      character.

PMID- 15260686
TI  - The low-lying electronic excited states of NiCO.
AB  - Highly correlated coupled cluster methods with single and double excitations
      (CSSD) and CCSD with perturbative triple excitations were used to predict
      molecular structures and harmonic vibrational frequencies for the electronic
      ground state X 1Sigma+, and for the 3Delta, 3Sigma+, 3Phi, 1 3Pi, 2 3Pi, 1Sigma+,
      1Delta, and 1Pi excited states of NiCO. The X 1Sigma+ ground state's geometry is
      for the first time compared with the recently determined experimental structure.
      The adiabatic excitation energies, vertical excitation energies, and dissociation
      energies of these excited states are predicted. The importance of pi and sigma
      bonding for the Ni-C bond is discussed based on the structures of excited states.

PMID- 15260687
TI  - Deflection and deceleration of hydrogen Rydberg molecules in inhomogeneous
      electric fields.
AB  - Hydrogen molecules are excited in a molecular beam to Rydberg states around n=17
      18 and are exposed to the inhomogeneous electric field of an electric dipole. The
      large dipole moment produced in the selected Stark eigenstates leads to strong
      forces on the H2 molecules in the inhomogeneous electric field. The trajectories
      of the molecules are monitored using ion-imaging and time of flight measurements.
      With the dipole rods mounted parallel to the beam direction, the high-field
      seeking and low-field-seeking Stark states are deflected towards and away from
      the dipole, respectively. The magnitude of the deflection is measured as a
      function of the parabolic quantum number k and of the duration of the applied
      field. It is also shown that a large deflection is observed when populating the
      (17d2)1 state at zero field and switching the dipole field on after a delay. With
      the dipole mounted perpendicular to the beam direction, the molecules are either
      accelerated or decelerated as they move towards the dipole. The Rydberg states
      are found to survive for over 100 micros after the dipole field is switched off
      before being ionized at the detector and the time of flight is measured. A
      greater percentage change in kinetic energy is achieved by initial seeding of the
      beam in helium or neon followed by inhomogeneous field deceleration/acceleration.
      Molecular dynamics trajectory simulations are presented highlighting the extent
      to which the trajectories can be predicted based on the known Stark map. The
      spectroscopy of the populated states is discussed in detail and it is established
      that the N+=2, J=1, MJ=0 states populated here have a special stability with
      respect to decay by predissociation.

PMID- 15260688
TI  - Cis-cis and trans-perp HOONO: action spectroscopy and isomerization kinetics.
AB  - The weakly bound HOONO product of the OH+NO2+M reaction is studied using the
      vibrational predissociation that follows excitation of the first OH overtone
      (2nu1). We observe formation of both cis-cis and trans-perp conformers of HOONO.
      The trans-perp HOONO 2nu1 band is observed under thermal (223-238 K) conditions
      at 6971 cm(-1). We assign the previously published (warmer temperature) HOONO
      spectrum to the 2nu1 band at 6365 cm(-1) and 2nu1-containing combination bands of
      the cis-cis conformer of HOONO. The band shape of the trans-perp HOONO spectrum
      is in excellent agreement with the predicted rotational contour based on previous
      experimental and theoretical results, but the apparent origin of the cis-cis
      HOONO spectrum at 6365 cm(-1) is featureless and significantly broader,
      suggesting more rapid intramolecular vibrational redistribution or
      predissociation in the latter isomer. The thermally less stable trans-perp HOONO
      isomerizes rapidly to cis-cis HOONO with an experimentally determined lifetime of
      39 ms at 233 K at 13 hPa (in a buffer gas of predominantly Ar). The temperature
      dependence of the trans-perp HOONO lifetime in the range 223-238 K yields an
      isomerization barrier of 33+/-12 kJ/mol. New ab initio calculations of the
      structure and vibrational mode frequencies of the transition state perp-perp
      HOONO are performed using the coupled cluster singles and doubles with
      perturbative triples [CCSD(T)] model, using a correlation consistent polarized
      triple zeta basis set (cc-pVTZ). The energetics of cis-cis, trans-perp, and perp
      perp HOONO are also calculated at this level [CCSD(T)/cc-pVTZ] and with a
      quadruple zeta basis set using the structure determined at the triple zeta basis
      set [CCSD(T)/cc-pVQZ//CCSD(T)/cc-pVTZ]. These calculations predict that the anti
      form of perp-perp HOONO has an energy of DeltaE0=42.4 kJ/mol above trans-perp
      HOONO, corresponding to an activation enthalpy of DeltaH298 (double dagger
      0)=41.1 kJ/mol. These results are in good agreement with statistical simulations
      based on a model developed by Golden, Barker, and Lohr. The simulated
      isomerization rates match the observed decay rates when modeled with a trans-perp
      to cis-cis HOONO isomerization barrier of 40.8 kJ/mol and a strong collision
      model. The quantum yield of cis-cis HOONO dissociation to OH and NO2 is also
      calculated as a function of photon excitation energy in the range 3500-7500 cm(
      1), assuming D0=83 kJ/mol. The quantum yield is predicted to vary from 0.15 to 1
      over the observed spectrum at 298 K, leading to band intensities in the action
      spectrum that are highly temperature dependent; however, the observed relative
      band strengths in the cis-cis HOONO spectrum do not change substantially with
      temperature over the range 193-273 K. Semiempirical calculations of the
      oscillator strengths for 2nu1(cis-cis HOONO) and 2nu1(trans-perp HOONO) are
      performed using (1) a one-dimensional anharmonic model and (2) a Morse oscillator
      model for the OH stretch, and ab initio dipole moment functions calculated using
      Becke, Lee, Yang, and Parr density functional theory (B3LYP), Moller-Plesset
      pertubation theory truncated at the second and third order (MP2 and MP3), and
      quadratic configuration interaction theory using single and double excitations
      (QCISD). The QCISD level calculated ratio of 2nu1 oscillator strengths of trans
      perp to cis-cis HOONO is 3.7:1. The observed intensities indicate that the
      concentration of trans-perp HOONO early in the OH+NO2 reaction is significantly
      greater than predicted by a Boltzmann distribution, consistent with statistical
      predictions of high initial yields of trans-perp HOONO from the OH+NO2+M
      reaction. In the atmosphere, trans-perp HOONO will isomerize nearly
      instantaneously to cis-cis HOONO. Loss of HOONO via photodissociation in the near
      IR limits the lifetime of cis-cis HOONO during daylight to less than 45 h, other
      loss mechanisms will reduce the lifetime further.

PMID- 15260689
TI  - Microwave spectra and the metal-hydrogen bond lengths for the C5H5Mo(CO)3H and
      C5H5W(CO)3H complexes.
AB  - The measurements of rotational spectra and metal-hydrogen bond lengths for
      molybdenum and tungsten hydride complexes were recently completed in our
      laboratory. The W-H and Mo-H bond lengths were obtained from high resolution
      rotational spectra of C5H5Mo(CO)3H, C5H5W(CO)3H, C5H5Mo(CO)3D, and C5H5W(CO)3D.
      Data for five molybdenum and four tungsten isotopomers were obtained for both the
      normal and deuterium-substituted species. The asymmetric-top rotational
      parameters A, B, C, DeltaJ, and deltaJ were determined from the least-squares
      fits and these results indicate that the structures of these complexes are nearly
      rigid. The hydrogen bond lengths were determined for both complexes using
      Kraitchman analyses. The molybdenum-hydrogen bond length for the C5H5Mo(CO)3H
      complex is rMo-H=1.80(1) A. The tungsten-hydrogen bond length for the C5H5W(CO)3H
      complex is rW-H=1.79(4) A. Density functional theory (DFT) calculations of the
      structures were performed to obtain the optimized theoretical structures for
      C5H5Mo(CO)3H and C5H5W(CO)3H. Results obtained from the DFT calculations are in
      good agreement with the experimental parameters, and the Mo-H value is in good
      agreement with previously reported Mo-H bond lengths for similar complexes.

PMID- 15260690
TI  - Numerical and experimental studies of long-range magnetic dipolar interactions.
AB  - We describe several numerical methods developed to analyze the behavior of spin
      polarized liquids in the presence of long-range magnetic dipolar interactions and
      external field gradients. Two of the methods use a discrete lattice of spins. In
      the first we calculate the magnetic field from the lattice of spins directly,
      either in the rotating frame, or in the lab frame. In the second method we
      include the dipolar fields from linear magnetization gradients analytically and
      calculate the dipolar fields from higher order gradients in Fourier space, where
      they are a local function of the magnetization. In the third method the
      magnetization is expanded in a Taylor series and the dipolar fields are
      calculated analytically for each term. The results of these calculations are
      compared to experimental data, in which we use two superconducting quantum
      interference device magnetometers adjacent to a spherical sample of
      hyperpolarized liquid 129Xe to detect the evolution of magnetization gradients.
      In particular, we observe an increase by a factor of 100 of the spin dephasing
      time in a longitudinal magnetic field gradient due to dipolar interactions of the
      spins. While each of the numerical techniques has certain limitations, they are
      generally in agreement with each other and with experimental data.

PMID- 15260691
TI  - Structure of liquid and glassy methanol confined in cylindrical pores.
AB  - We present a neutron scattering analysis of the density and the static structure
      factor of confined methanol at various temperatures. Confinement is performed in
      the cylindrical pores of MCM-41 silicates with pore diameters D=24 and 35 A. A
      change of the thermal expansivity of confined methanol at low temperature is the
      signature of a glass transition, which occurs at higher temperature for the
      smallest pore. This is evidence of a surface induced slowing down of the dynamics
      of the fluid. The structure factor presents a systematic evolution with the pore
      diameter, which has been analyzed in terms of excluded volume effects and fluid
      matrix cross correlation. Conversely to the case of Van der Waals fluids, it
      shows that stronger fluid-matrix correlations must be invoked most probably in
      relation with the H-bonding character of both methanol and silicate surface.

PMID- 15260692
TI  - Thermally stimulated exoelectron emission from solid neon.
AB  - In spite of the negative electron affinity of Ne atoms, appreciable
      concentrations of electrons can be trapped in solid neon layers formed by
      depositing the gas on a cold substrate with concurrent electron irradiation.
      These are trapped at defect sites, and can be promoted into the conduction band
      in an annealing experiment. They can then recombine with positive charges
      producing vacuum ultraviolet "thermoluminescence," but can also be extracted from
      the solid, and detected as an "exoelectron" current. The thermally stimulated
      exoelectron emission profiles of the electron current versus temperature reveal
      two broad features near 7.5 and 10 K. These are shown to correspond to two
      distributions of electron trapping sites with slightly differing activation
      energies. For the narrower, higher temperature maximum, an average activation
      energy of about 23 meV is deduced, in good agreement with predictions based on
      the theory of electronic defect formation.

PMID- 15260693
TI  - Thermodynamic and structural properties of repulsive hard-core Yukawa fluid:
      integral equation theory, perturbation theory and Monte Carlo simulations.
AB  - The thermodynamic and structural properties of purely repulsive hard-core Yukawa
      particles in the fluid state are determined through Monte Carlo simulation and
      modeled using perturbation theory and integral equation theory in the mean
      spherical approximation (MSA). Systems of particles with Yukawa screening lengths
      of 1.8, 3.0, and 5.0 are examined with results compared to variations of MSA and
      perturbation theory. Thermodynamic properties were predicted well by both
      theories in the fluid region up to the fluid-solid phase boundary. Further, we
      found that a simplified exponential version of the MSA is the most accurate at
      predicting radial distribution function at contact. Radial distribution function
      of repulsive hard-core Yukawa particles are also reported. The results show that
      methods based on MSA and perturbation theory that are typically applied to the
      attractive hard-core Yukawa potential can also be extended to the purely
      repulsive hard-core Yukawa potential.

PMID- 15260694
TI  - Specific heat and Lindemann-like parameter of metallic clusters: mono- and
      polyvalent metals.
AB  - The Brownian-type molecular dynamics simulation is revisited and applied to study
      the thermal and geometric properties of four mono- and two polyvalent metallic
      clusters. For the thermal property, we report the specific heat at constant
      volume CV and study the solid-liquid-like transition by scrutinizing its
      characteristic. For the geometric property, we calculate the root mean square
      relative bond-length fluctuation delta as a function of increasing temperature.
      The thermal change in delta reflects the movement of atoms and hence is a
      relevant parameter in understanding the phase transition in clusters. The
      simulated results for the CV of alkali and aluminum clusters whose ground state
      structures exhibit icosahedral symmetry generally show one phase transition. In
      contrast, the tetravalent lead is quite often seen to exhibit two phase
      transitions, a premelting process followed by a progressive melting. In
      connection with the premelting scenario, it is found here that those (magic
      number) clusters identified to be of lesser stability (among other stable ones)
      according to the second energy difference are clusters showing a greater
      possibility of undergoing premelting process. This energy criterion applies to
      aluminum clusters nAl=28 and 38. To delve further into the thermal behavior of
      clusters, we have analyzed also the thermal variation of deltaT and attempted to
      correlate it with CV(T). It turns out that the premelting (if exist) and melting
      temperatures of the smaller size clusters (n less, similar 50) extracted from CV
      do not always agree quantitatively with that deduced from delta.

PMID- 15260695
TI  - Quantum aspects of self-organized periodic chemical reactions.
AB  - It is a remarkable empirical fact, known for a long time, that in certain self
      organized periodic chemical reactions, such as Liesegang's or Belousov
      Zhabotinsky's reactions, the product of molecular weight of precipitate,
      precipitation length period, and speed of precipitation is of the order of
      universal Planck's quantum of action h. Based on the fact that the classical and
      quantum diffusions are processes, which are indistinguishable in the
      configuration space, a quantum criterion in terms of diffusion constants has been
      established. This criterion enables one to find out conditions under which the
      quantum behavior of self-organized periodic reactions can be observed.

PMID- 15260696
TI  - The vibrational spectrum of NF3 and the manifestation of resonant dipole-dipole
      interaction in NF3 solutions in liquid argon.
AB  - Vibrational spectra of trifluoramine, NF3, dissolved in liquid Ar were studied at
      90 K in the concentration range between 2 x 10(-5) and 0.1 mole fraction, using
      Fourier transform spectroscopy. The concentration dependence of the band shapes
      in the region of the combination transitions nu1+nu3, nu2+nu3, and 2nu3 involving
      the strong nu3 mode was studied and the absorption associated with NF3 dimers was
      isolated. This absorption is compared with spectra of NF3 dimers calculated on
      the basis of resonant dipole-dipole interaction between two doubly degenerate
      oscillators. Spectra of pure liquid NF3 were recorded for comparison. Using the
      nu1+nu3 absorption band of the NF3 dimer the distance R between two NF3 molecules
      was determined to be R=4.5(1) A in solution in liquid Ar. This distance is
      compared with the separation between two NF3 molecules in liquid NF3 and with the
      value calculated from the pair distribution function obtained from Monte Carlo
      simulations.

PMID- 15260697
TI  - Accurate theoretical prediction of vibrational frequencies in an inhomogeneous
      dynamic environment: a case study of a glutamate molecule in water solution and
      in a protein-bound form.
AB  - We propose a hierarchical approach to model vibrational frequencies of a ligand
      in a strongly fluctuating inhomogeneous environment such as a liquid solution or
      when bound to a macromolecule, e.g., a protein. Vibrational frequencies typically
      measured experimentally are ensemble averaged quantities which result (in part)
      from the influence of the strongly fluctuating solvent. Solvent fluctuations can
      be sampled effectively by a classical molecular simulation, which in our model
      serves as the first, low level of the hierarchy. At the second high level of the
      hierarchy a small subset of system coordinates is used to construct a patch of
      the potential surface (ab initio) relevant to the vibration in question. This
      subset of coordinates is under the influence of an instantaneous external force
      exerted by the environment. The force is calculated at the lower level of the
      hierarchy. The proposed methodology is applied to model vibrational frequencies
      of a glutamate in water and when bound to the Glutamate receptor protein and its
      mutant. Our results are in close agreement with the experimental values and
      frequency shifts measured by the Jayaraman group by the Fourier transform
      infrared spectroscopy [Q. Cheng et al., Biochem. 41, 1602 (2002)]. Our
      methodology proved useful in successfully reproducing vibrational frequencies of
      a ligand in such a soft, flexible, and strongly inhomogeneous protein as the
      Glutamate receptor.

PMID- 15260698
TI  - Binary phase behavior and aggregation of dilute methanol in supercritical carbon
      dioxide: a Monte Carlo simulation study.
AB  - Configurational-bias Monte Carlo simulations in the Gibbs and isobaric-isothermal
      ensembles using the transferable potentials for phase equilibria force field were
      carried out to investigate the thermophysical properties of mixtures containing
      supercritical carbon dioxide and methanol. The binary vapor-liquid coexistence
      curves were calculated at 333.15 and 353.15 K and are in excellent agreement with
      experimental measurements. The self-association of methanol in supercritical
      carbon dioxide was investigated over a range of temperatures and pressures near
      the mixture critical point. The temperature dependence of the equilibrium
      constants for the formation of hydrogen-bonded aggregates (from dimer to
      heptamer) allowed for the determination of the enthalpy of hydrogen bonding,
      DeltaHHB, in supercritical carbon dioxide with values for DeltaHHB of about 15 kJ
      mol(-1) falling within the range of previously proposed values. No strong
      pressure dependence was observed for the formation of aggregates. Apparently the
      decrease of the entropic penalty and of the enthalpic benefit upon increasing
      pressure or solvent density mostly cancel each other's effect on aggregate
      formation.

PMID- 15260699
TI  - Structures and correlation functions of multicomponent and polydisperse hard
      sphere mixtures from a density functional theory.
AB  - The structures of nonuniform binary hard-sphere mixtures and the correlation
      functions of uniform ternary hard-sphere mixtures were studied using a modified
      fundamental-measure theory based on the weight functions of Rosenfeld [Rosenfeld,
      Phys. Rev. Lett. 63, 980 (1989)] and Boublik-Mansoori-Carnahan-Starling-Leland
      equation of state [Boublik, J. Chem. Phys. 53, 471 (1970); Mansoori et al., J.
      Chem. Phys. 54, 1523 (1971)]. The theoretical predictions agreed very well with
      the molecular simulations for the overall density profiles, the local
      compositions, and the radial distribution functions of uniform as well as
      inhomogeneous hard-sphere mixtures. The density functional theory was further
      extended to represent the structure of a polydisperse hard-sphere fluid near a
      hard wall. Excellent agreement was also achieved between theory and Monte Carlo
      simulations. The density functional theory predicted oscillatory size
      segregations near a hard wall for a polydisperse hard-sphere fluid of a uniform
      size distribution.

PMID- 15260700
TI  - Lifetimes of cagelike water clusters immersed in bulk liquid water: a molecular
      dynamics study on gas hydrate nucleation mechanisms.
AB  - Molecular dynamics simulations were performed to observe the evolution of
      cagelike water clusters immersed in bulk liquid water at 250 and 230 K. Totally,
      we considered four types of clusters--dodecahedral (5(12)) and tetrakaidecahedral
      (5(12)6(2)) cagelike water clusters filled with or without a methane molecule,
      respectively. The lifetimes of these clusters were calculated according to their
      Lindemann index (delta) using the criterion of delta> or =0.07. The lifetimes of
      the clusters at 230 K are longer than that at 250 K, and their ratios are the
      same as the ratio of structure relaxation times of bulk water at these
      temperatures. For both the filled and empty clusters, the lifetimes of 5(12)6(2)
      cagelike clusters are similar to that of 5(12) cagelike clusters. Although the
      methane molecules indeed make the filled cagelike water clusters live longer than
      the empty ones, the empty cagelike water clusters still have the chance of being
      long lived. These observations support the cluster nucleation hypothesis for the
      formation mechanisms of gas hydrates.

PMID- 15260701
TI  - A consistent integral equation theory for hard spheres.
AB  - The standard integral equation approach is used to extract the bridge function
      and other correlation functions of hard spheres fluid. To achieve this, we first
      use a recent consistent closure relation proposed by Bomont et al. [J. Chem.
      Phys. 119, 2188 (2003)] that has already proven to be accurate to describe the
      Lennard-Jones fluid properties. Second, we take advantage of the coherent scheme
      derived by Bomont [J. Chem. Phys. 119, 11484 (2003)] to calculate the excess
      chemical potential, the entropy and some relative transport properties. Very good
      agreement is obtained for structural quantities and thermodynamic properties as
      compared to exact data at densities ranging from 0.1 to 0.9.

PMID- 15260702
TI  - Abnormal IR effects of Pt nanostructured surfaces upon CO chemisorption due to
      interaction and electron-hole damping.
AB  - The abnormal IR effects (AIREs) characterized by a positive-going peak of
      platinum (Pt) nanostructured surface generated in a square-wave potential
      treatment upon CO molecule chemisorption was observed and analyzed with a
      consideration of the interparticle interaction and electron-hole damping between
      nanoislands and CO molecules. A theoretical simulation shows that the islanded
      nanostructured Pt surfaces, which gives rise to interparticle interaction,
      coupling with electron-hole mechanism, may contribute to the origins of positive
      going peak (AIREs) observed by in situ Fourier transformation IR (FTIR)
      experiments.

PMID- 15260703
TI  - Theoretical study of the reaction of acrylonitrile on Si(001).
AB  - Two recent experiments for adsorbed acrylonitrile on the Si(001) surface reported
      different adsorption structures at 110 and 300 K. We investigate the reaction of
      acrylonitrile on Si(001) by first-principles density-functional calculations. We
      find that the so-called [4+2] structure in which acrylonitrile resides between
      two dimer rows is not only thermodynamically favored over other structural models
      but also easily formed via a precursor where the N atom of acrylonitrile is
      attached to the down atom of the Si dimer. The additional initial-state theory
      calculation for the C 1s core levels of adsorbed acrylonitrile provides an
      interpretation for the observed low- and room-temperature adsorption
      configurations in terms of the precursor and [4+2] structures, respectively.

PMID- 15260705
TI  - Aging correlation functions for blinking nanocrystals, and other on-off
      stochastic processes.
AB  - Following recent experiments on power law blinking behavior of single
      nanocrystals, we calculate two-time intensity correlation functions I(t)I(t+t')
      for these systems. We use a simple two state (on and off) stochastic model to
      describe the dynamics. We classify possible behaviors of the correlation function
      and show that aging, e.g., dependence of the correlation function on age of
      process t, is obtained for classes of the on time and off time distributions
      relevant to experimental situation. Analytical asymptotic scaling behaviors of
      the intensity correlation in the double time t and t' domain are obtained. In the
      scaling limit I(t)I(t+t('))-->h(x), where four classes of behaviors are found:
      (i) finite averaged on and off times x=t' (standard behavior); (ii) on and off
      times with identical power law behaviors x=t/t' (case relevant for capped
      nanocrystals); (iii) exponential on times and power law off times x=tt' (case
      relevant for uncapped nanocrystals); (iv) for defected off time distribution we
      also find x=t+t'. Origin of aging behavior is explained based on simple diffusion
      model. We argue that the diffusion controlled reaction A+B <==>AB, when followed
      on a single particle level exhibits aging behavior.

PMID- 15260704
TI  - Rate constant for diffusion-influenced ligand binding to receptors of arbitrary
      shape on a cell surface.
AB  - The theory of ligand binding to receptors on a cell surface suggested by Berg and
      Purcell and generalized by Zwanzig and Szabo uses the assumption that receptors
      are circular absorbing disks on an otherwise reflecting sphere. One of the key
      ingredients of this theory is a solution for the rate constant for ligand binding
      to a single circular receptor on a reflecting plane. We give an exact solution
      for the rate constant for binding to a single elliptic receptor and an
      approximate solution for binding to a single receptor of more general shape. The
      latter was tested by Brownian dynamics simulations. We found that the approximate
      formula predicted the rate constant with better than 10% accuracy for all studied
      receptor shapes. Using our solutions one can find the rate constant for ligand
      binding to a cell covered by N noncircular receptors by means of the Zwanzig
      Szabo formula.

PMID- 15260706
TI  - Molecular alignment of rigid rods in nonrigid spherical pores.
AB  - We have investigated the orientation ordering of two shish-kebab chains confined
      by spherically harmonic potentials through Monte Carlo simulations and asymptotic
      analysis. The rigid rod is modeled as shish-kebab chains consisting of tangent
      hard spheres aligned in the same axis, and the harmonic potential is chosen to
      model nonrigid cavities. We first show that the interactions between a rod and
      the spherically harmonic potential are independent of chain orientation,
      indicating that the alignment of two confined rods arises from the excluded
      volume interactions alone. In the strong fields, the order parameter of two
      confined rods converges to different values, depending on the parity of chain
      length. From asymptotic order parameters, we find that the rods of odd-number
      beads rotate more freely even under the limiting strong confinement. However, the
      two rods of even-number beads are essentially trapped in a configuration of
      perpendicular alignment through intercalation of their central grooves. We
      attribute the dependence of the parity of chain length to the different locations
      of the center-of-mass in a rod for these two cases. Furthermore, we compare the
      shish-kebab chains with different rod models in the simulations, and utilize
      these models to explore the effect of the local rod smoothness on molecular
      alignment. Our findings suggest that increasing local rod smoothness enhances the
      rotational degree of freedom for confined rods, and the effect of local rod
      roughness emerges under strong enough applied potentials.

PMID- 15260707
TI  - Nucleation kinetics of folded chain crystals of polyethylene on active centers.
AB  - Kinetic equations describing formation of nuclei of a new phase on active centers
      from supercooled melt taking into account exhaustion of active centers are solved
      numerically. Basic characteristics of nucleation process (total number of nuclei
      and nucleation rate) of folded chain crystals of polyethylene at low supercooling
      are determined and compared with measured data. Our model gives good coincidence
      with experimental measurements of the total number density of nuclei. Nucleation
      rate reaches some quasistationary limit at sufficiently long time, which is
      approximately 20% of the stationary nucleation rate determined by the standard
      way.

PMID- 15260708
TI  - A Monte Carlo study of fluctuating polymer-grafted membranes.
AB  - Using Monte Carlo simulations of an off-lattice model, we study the elastic
      properties of polymer-grafted membranes. Our results are found to be in good
      agreement with those predicted by the classical path approximation of the self
      consistent field theory and scaling theory based on de Gennes' blob picture. In
      particular, we found that when the membrane is grafted on both sides by brushes
      with same molecular weight N and grafting density sigma, the excess bending
      modulus induced by the polymers scales as N3 sigmaalpha where alpha is consistent
      with 7/3, as predicted by the self-consistent field theory, and 5/2, as predicted
      by the scaling theory. When the polymers are grafted to one side of the membrane
      only, the membrane bends away from the polymers with a spontaneous curvature with
      a scaling that is consistent with both scaling and self-consistent field
      theories. When the thickness of the brush exceeds the membrane's spontaneous
      radius of curvature, the bending modulus approaches a constant which is of the
      same order as the bending modulus of the bare membrane.

PMID- 15260709
TI  - Charge and energy dynamics in photo-excited poly(para-phenylenevinylene) systems.
AB  - We report results from simulations of charge and energy dynamics in poly(para
      phenylenevinylene) (PPV) and PPV interacting with C60. The simulations were
      performed by solving the time-dependent Schrodinger equation and the lattice
      equation of motion simultaneously and nonadiabatically. The electronic system and
      the coupling of the electrons to the lattice were described by an extended three
      dimensional version of the Su-Schrieffer-Heeger model, which also included an
      external electric field. Electron and lattice dynamics following electronic
      excitations at different energies have been simulated. The effect of additional
      lattice energy was also included in the simulations. Our results show that both
      exciton diffusion and transitions from high to lower lying excitations are
      stimulated by increasing the lattice energy. Also field induced charge separation
      occurs faster if the lattice energy is increased. This separation process is
      highly nonadiabatic and involves a significant rearrangement of the electron
      distribution. In the case of PPV coupled to C60, we observe a spontaneous charge
      separation. The separation time is in this case limited by the local
      concentration of C60 molecules close to the PPV chain.

PMID- 15260710
TI  - Long-range ordered structures in diblock copolymer melts induced by combined
      external fields.
AB  - The structure of diblock copolymer melts under a single external electric or
      shear field, as well as under combined orthogonal external fields was
      investigated using a cell dynamic system. The phase structure was determined by
      coupling the effects of the external fields with the original structure of the
      bulk free of external fields. The single electric or shear field generated long
      range cylinders in asymmetric A4mB6m diblock copolymers and distorted lamellae in
      symmetric A5mB5m diblock copolymers. Successive orthogonal shear followed by an
      electric external field generated long-range lamellae in symmetrical A5mB5m
      systems. However, the simultaneous orthogonal electric and shear fields could
      more easily form long-range lamellae than the sequential orthogonal fields. The
      dynamical processes in diblock copolymer melts under orthogonal fields have been
      also examined.

PMID- 15260711
TI  - Dynamical origin of enhanced conformational searches of Tsallis statistics
      sampling.
AB  - The characteristic sampling dynamics of importance samplings driven by the
      Tsallis weight [C. Tsallis, J. Stat. Phys. 52, 479 (1988)] has been analyzed in
      terms of recently developed Langevin stochastic model by considering the effects
      of the density of states and the potential smoothing of the Tsallis
      transformation. Our study reveals that the fixed points, which are determined by
      the crossing points of the statistical temperature and the Tsallis effective
      temperature, play a critical role in overall dynamics of the Tsallis statistics
      sampling. The dynamical origin of enhanced conformational searches of the Tsallis
      weight has been investigated by unveiling the intimate relationship between the
      sampling dynamics and the stability change of corresponding fixed points. Based
      on this stochastic analysis, we propose one effective method to realize a broad
      energy distribution in the Tsallis statistics sampling by determining optimal
      Tsallis parameters systematically based on preliminary canonical samplings. The
      effectiveness of our method has been validated in the folding simulation of Met
      Enkephalin and liquid-solid transition simulation of Lennard-Jones cluster
      systems.

PMID- 15260712
TI  - The Adam-Gibbs equation and the out-of-equilibrium alpha relaxation of glass
      forming systems.
AB  - The temperature dependence of the alpha-relaxation time out of equilibrium has
      been investigated by means of dielectric relaxation in a series of fragile glass
      formers including several polymers. The influence of physical aging on this
      behavior has also been studied. The experimental results have been quantitatively
      compared with the predictions of the Adam-Gibbs equation. It has been found that,
      whereas for small molecule glass formers the experimental values of the apparent
      activation energy agree quite well with the prediction of the Adam-Gibbs
      equation, for polymers the experimental activation energy values are
      systematically higher. Moreover, whereas for small molecule glass formers the
      experimental values of the apparent activation energy remains essentially
      unaffected by physical aging, for polymers a pronounced reduction of the
      experimental apparent activation energy is observed. These results are found to
      be consistent with the Adam-Gibbs equation if a significant temperature variation
      of the configurational entropy in the investigated temperature range would occur
      for nonannealed polymers, being the possible variation hardly noticeable for the
      small molecules. With this assumption, all the obtained results would support the
      validity of the Adam-Gibbs equation for describing the temperature dependence of
      the time scale of the alpha-relaxation also out of equilibrium, at least for
      fragile glass formers.

PMID- 15260713
TI  - Comment on "Multicomponent nucleation: Thermodynamically consistent description
      of the nucleation work" [J. Chem. Phys. 120, 3749 (2004)].
AB  - In the above cited paper, Kashchiev extends the "thermodynamically consistent"
      description of nucleation work to phase formation processes in multicomponent
      systems. It is claimed that this approach is generally applicable widely
      independent on the kind of phase transformation considered. In contrast to this
      statement, it is shown in our Comment that Kashchiev's approach is theoretically
      not well founded. It contains, in addition, a number of assumptions, which are
      not generally fulfilled. Because of this his method cannot give, in general, a
      satisfactory determination of the work of critical cluster formation in
      nucleation theory. An experimental example is given verifying our conclusions.

PMID- 15260714
TI  - Evaluation of multicenter one-electron integrals of noninteger u screened Coulomb
      type potentials and their derivatives over noninteger n Slater orbitals.
AB  - Multicenter integrals over noninteger n Slater type orbitals with integer and
      noninteger values of indices u of screened Coulomb type potentials,
      f(u)(eta,r)=r(u-1)e(-etar), and their first and second derivatives with respect
      to Cartesian coordinates of the nuclei of a molecule are described. Using
      complete orthonormal sets of Psi(alpha) exponential type orbitals and rotation
      transformation of two-center overlap integrals, these integrals are expressed
      through the noncentral potential functions depending on the molecular auxiliary
      functions A(k) and B(k). The series expansion formulas derived for molecular
      integrals of screened Coulomb potentials and their derivatives are especially
      useful for the computation of multicenter electronic attraction, electric field,
      and electric field gradient integrals. The convergence of series is tested for
      arbitrary values of parameters of potentials and orbitals.

PMID- 15260715
TI  - Approximate generation of full-dimensional ab initio van der Waals surfaces for
      high-resolution spectroscopy.
AB  - A method for the generation of highly accurate, nearly-exact, full-dimensional
      interaction energy surfaces for weakly interacting subsystems is proposed. The
      method is based on the local expansion of the exact interaction energy surface in
      the Taylor series with respect to intramolecular coordinates. It is shown that
      without any significant loss of accuracy this expansion can be limited to a few
      low-order terms. This leads to significant savings in computations of the full
      dimensional interaction energy surfaces. Also a method for the direct calculation
      of the interaction energy surface of reduced dimensionality, corresponding to
      averaging over the intramolecular vibrations, without explicit knowledge of the
      full-dimensional surface, is presented. The main ideas and computational features
      of the proposed scheme are comprehensively tested for the Ar-HF system.

PMID- 15260716
TI  - Sign-consistent dynamical couplings between ab initio three-center wave
      functions.
AB  - We present a method to ensure the sign consistency of dynamical couplings between
      ab initio three-center wave functions. The method also allows to systematically
      "diabatize" avoided crossings between two potential energy surfaces, including
      conical intersections. Illustrations are presented for H(3)(+), LiH(2)(+), and
      NH(2)(5+) quasimolecules.

PMID- 15260717
TI  - Fock space multireference coupled cluster method with full inclusion of connected
      triples for excitation energies.
AB  - We report the initial Fock space multireference coupled cluster method with the
      full inclusion of single, double, and triple excitations (FS-CCSDT) for the (1,1)
      sector. We present pilot applications for calculating excitation energies for the
      N(2) molecule and the Ne atom. The performance of the current model, along with
      the FS-CCSD one, has been studied in comparison with the equation-of-motion
      coupled-cluster and the similarity transformed methods.

PMID- 15260718
TI  - Quantum tunneling dynamics in multidimensional systems: a matching-pursuit
      description.
AB  - Rigorous simulations of quantum tunneling dynamics in model systems with up to 20
      coupled degrees of freedom are reported. The simulations implement an extension
      of the recently developed matching-pursuit/split-operator Fourier-transform
      method to complex-valued coherent-state representations. The resulting method
      recursively applies the time-evolution operator, as defined by the Trotter
      expansion to second order accuracy, in dynamically adaptive coherent-state
      representations generated by an approach that combines the matching-pursuit
      algorithm with a gradient-based optimization method.

PMID- 15260719
TI  - Anharmonic quantum contribution to vibrational dephasing.
AB  - Based on a quantum Langevin equation and its corresponding Hamiltonian within a c
      number formalism we calculate the vibrational dephasing rate of a cubic
      oscillator. It is shown that leading order quantum correction due to
      anharmonicity of the potential makes a significant contribution to the rate and
      the frequency shift. We compare our theoretical estimates with those obtained
      from experiments for small diatomics N(2), O(2), and CO.

PMID- 15260720
TI  - Quantum dynamics calculations using symmetrized, orthogonal Weyl-Heisenberg
      wavelets with a phase space truncation scheme. II. Construction and optimization.
AB  - In this paper, we extend and elaborate upon a wavelet method first presented in a
      previous publication [B. Poirier, J. Theo. Comput. Chem. 2, 65 (2003)]. In
      particular, we focus on construction and optimization of the wavelet functions,
      from theoretical and numerical viewpoints, and also examine their localization
      properties. The wavelets used are modified Wilson-Daubechies wavelets, which in
      conjunction with a simple phase space truncation scheme, enable one to solve the
      multidimensional Schrodinger equation. This approach is ideally suited to
      rovibrational spectroscopy applications, but can be used in any context where
      differential equations are involved.

PMID- 15260721
TI  - Quantum dynamics calculations using symmetrized, orthogonal Weyl-Heisenberg
      wavelets with a phase space truncation scheme. III. Representations and
      calculations.
AB  - In a previous paper [J. Theo. Comput. Chem. 2, 65 (2003)], one of the authors
      (B.P.) presented a method for solving the multidimensional Schrodinger equation,
      using modified Wilson-Daubechies wavelets, and a simple phase space truncation
      scheme. Unprecedented numerical efficiency was achieved, enabling a ten
      dimensional calculation of nearly 600 eigenvalues to be performed using direct
      matrix diagonalization techniques. In a second paper [J. Chem. Phys. 121, 1690
      (2004)], and in this paper, we extend and elaborate upon the previous work in
      several important ways. The second paper focuses on construction and optimization
      of the wavelength functions, from theoretical and numerical viewpoints, and also
      examines their localization. This paper deals with their use in representations
      and eigenproblem calculations, which are extended to 15-dimensional systems. Even
      higher dimensionalities are possible using more sophisticated linear algebra
      techniques. This approach is ideally suited to rovibrational spectroscopy
      applications, but can be used in any context where differential equations are
      involved.

PMID- 15260722
TI  - Electron pair localization function: a practical tool to visualize electron
      localization in molecules from quantum Monte Carlo data.
AB  - In this work we introduce an electron localization function describing the
      pairing of electrons in a molecular system. This function, called "electron pair
      localization function," is constructed to be particularly simple to evaluate
      within a quantum Monte Carlo framework. Two major advantages of this function are
      the following: (i) the simplicity and generality of its definition; and (ii) the
      possibility of calculating it with quantum Monte Carlo at various levels of
      accuracy (Hartree-Fock, multiconfigurational wave functions, valence bond,
      density functional theory, variational Monte Carlo with explicitly correlated
      trial wave functions, fixed-node diffusion Monte Carlo, etc). A number of
      applications of the electron pair localization function to simple atomic and
      molecular systems are presented and systematic comparisons with the more standard
      electron localization function of Becke and Edgecombe are done. Results
      illustrate that the electron pair localization function is a simple and practical
      tool for visualizing electronic localization in molecular systems.

PMID- 15260723
TI  - Theoretical investigation of substituted anthraquinone dyes.
AB  - We have investigated with computational chemistry techniques the visible spectra
      of substituted anthraquinones. A wide panel of theoretical methods has been used,
      with various basis sets and density functional theory (DFT) functionals, in order
      to assess a level of theory that would lead to converged excitation energies. It
      turns out that the hybrid Becke-Lee-Yang-Parr and Perdew-Burke-Erzenrhof
      functionals with the 6-31G (d,p) atomic basis set provide reliable lambda(max)
      when the solvent effects are included in the model. Combining the results of both
      DFT schemes allows the prediction of lambda(max) with a standard deviation
      limited to 13 nm.

PMID- 15260724
TI  - Intermolecular interaction in an open-shell pi-bound cationic complex: IR
      spectrum and coupled cluster calculations for C2H2+-Ar.
AB  - The intermolecular potential energy surface (PES) of Ar interacting with the
      acetylene cation in its (2)Pi(u) ground electronic state is characterized by
      infrared photodissociation (IRPD) spectroscopy and quantum chemical calculations.
      In agreement with the theoretical predictions, the rovibrational analysis of the
      IRPD spectrum of C(2)H(2) (+)-Ar recorded in the vicinity of the antisymmetric CH
      stretching fundamental (nu(3)) is consistent with a vibrationally averaged T
      shaped structure and a ground-state center-of-mass separation of R(c.m.) = 2.86
      +/- 0.09 A. The nu(3) band experiences a blueshift of 16.7 cm(-1) upon
      complexation, indicating that vibrational excitation slightly reduces the
      interaction strength. The two-dimensional intermolecular PES of C(2)H(2) (+)-Ar,
      obtained from coupled cluster calculations with a large basis set, features
      strong angular-radial coupling and supports in addition to a global pi-bound
      minimum also two shallow side wells with linear H-bound geometries. Bound state
      rovibrational energy level calculations are carried out for rotational angular
      momentum J = 0-10 (both parities) employing a discrete variable representation
      distributed Gaussian basis method. Effective spectroscopic constants are
      determined for the vibrational ground state by fitting the calculated rotational
      energies to the standard Watson A-type Hamiltonian for a slightly asymmetric
      prolate top.

PMID- 15260725
TI  - Intramolecular vibrational energy redistribution in bridged azulene-anthracene
      compounds: ballistic energy transport through molecular chains.
AB  - Intramolecular vibrational energy flow in excited bridged azulene-anthracene
      compounds is investigated by time-resolved pump-probe laser spectroscopy. The
      bridges consist of molecular chains and are of the type (CH(2))(m) with m up to 6
      as well as (CH(2)OCH(2))(n) (n=1,2) and CH(2)SCH(2). After light absorption into
      the azulene S(1) band and subsequent fast internal conversion, excited molecules
      are formed where the vibrational energy is localized at the azulene side. The
      vibrational energy transfer through the molecular bridge to the anthracene side
      and, finally, to the surrounding medium is followed by probing the red edge of
      the azulene S(3) absorption band at 300 nm and/or the anthracene S(1) absorption
      band at 400 nm. In order to separate the time scales for intramolecular and
      intermolecular energy transfer, most of the experiments were performed in
      supercritical xenon where vibrational energy transfer to the bath is comparably
      slow. The intramolecular equilibration proceeds in two steps. About 15%-20% of
      the excitation energy leaves the azulene side within a short period of 300 fs.
      This component accompanies the intramolecular vibrational energy redistribution
      (IVR) within the azulene chromophore and it is caused by dephasing of normal
      modes contributing to the initial local excitation of the azulene side and
      extending over large parts of the molecule. Later, IVR in the whole molecule
      takes place transferring vibrational energy from the azulene through the bridge
      to the anthracene side and thereby leading to microcanonical equilibrium. The
      corresponding time constants tau(IVR) for short bridges increase with the chain
      length. For longer bridges consisting of more than three elements, however,
      tau(IVR) is constant at around 4-5 ps. Comparison with molecular dynamics
      simulations suggests that the coupling of these chains to the two chromophores
      limits the rate of intramolecular vibrational energy transfer. Inside the bridges
      the energy transport is essentially ballistic and, therefore, tau(IVR) is
      independent on the length.

PMID- 15260726
TI  - Ultrafast predissociation dynamics of water molecules excited to the electronic C
      and D states.
AB  - Two-photon excitation with femtosecond laser pulses in the spectral range 240-250
      nm was used to prepare vapor phase H(2)O and D(2)O in the C (1)B(1) and D (1)A(1)
      states. Both states are predissociated via the B (1)A(1) state, forming excited
      OH/OD(A (2)Sigma(+)) as well as ground state OH/OD(X (2)Pi). We used ultrashort
      infrared probe pulses (1.65-2.42 microm) to control the ratio between these
      excited and ground state fragments originating from the dissociation process.
      Time resolved detection of the OH/OD(A (2)Sigma(+)) --> OH/OD(X (2)Pi)
      fluorescence allows us to monitor the dynamics of the predissociation. For the
      heterogeneous predissociation out of the C(1)B(1) state life times of (0.5 +/-
      0.1) ps and (1.2 +/- 0.1) ps were found for H(2)O and D(2)O, respectively. The
      purely homogeneous character of the predissociation out of the D (1)A(1) state
      was monitored.

PMID- 15260727
TI  - Theoretical determination of highly excited states of K2 correlated adiabatically
      above K4p + K4p.
AB  - The electronic structure of the K(2) molecule is revisited to describe the 36
      highly excited states dissociating into the three limits K(4s) + K(4f), K(4s) +
      K(6p), and K(4s) + K(5d), which have not yet been investigated theoretically.
      Potential energy curves and spectroscopic constants are (re)displayed for the
      98(1,3)Lambda(g,u) ((+,-)) molecular states correlated adiabatically to the
      limits up to K(4s) + K(5d). For the 10 states dissociating adiabatically into
      K(4p) + K(4p) and limits above for which experimental data are available,
      averaged errors of present results are found to be Delta R(e) = 0.07a(0), Delta
      T(e) = 50 cm(-1), Delta omega(e) = 0.8 cm(-1) and Delta D(e) = 60 cm(-1). Full
      energy data are available at the following address http://lasim.univ
      lyon1.fr/allouche/k2.html

PMID- 15260728
TI  - Theoretical investigations of the N2H2+ cation and of its reactivity.
AB  - Accurate ab initio calculations have been performed in order to investigate both
      the stable isomers and the reactivity of the N(2)H(2)(+) cation. In addition to
      the trans-HNNH(+) isomer already observed in the photoelectron studies, a
      formaldehyde type (isodiazene cation) and H(2)O(2)-like isomers are found. At the
      coupled cluster level of theory, the isodiazene cation is calculated to be as
      stable as trans-HNNH(+). We have also studied the reactivity of N(2)H(2)(+) and
      its implication on the reactive processes involving N(2)/N(2)(+) and
      H(2)(+)/H(2), H/H(+) and HN(2)(+)/HN(2), and HN and HN(+) by performing suitable
      one-dimensional cuts of the six-dimensional potential energy functions of the
      lowest electronic states of H(2)N(2)(+). We have pointed out the crucial role of
      this tetratomic intermediate cation and the importance of the short range
      internuclear distances during these processes. In the case of N(2)/N(2)(+) and
      H(2)(+)/H(2) reactions, we have shown that the initial orientation of the
      reactants may influence the N(2)H(2)(+) tetratomic intermediate: One can expect
      to form the trans isomer preferentially if the internuclear axes of the
      H(2)/H(2)(+) and the N(2)(+)/N(2) molecules are parallel to each other when these
      diatoms are colliding and after intramolecular isomerization process. However, if
      the internuclear axes of the diatomics are perpendicular to each other, the
      isodiazene cation is formed preferentially. Different branching ratios are
      expected for each collision scheme. These reactive processes are found to involve
      vibronic, Renner-Teller and spin-orbit couplings between the electronic states of
      N(2)H(2)(+). These interactions mix these electronic states, leading to the
      formation of atomic, diatomic, and triatomic species via the decomposition of the
      N(2)H(2)(+) intermediate complex.

PMID- 15260729
TI  - Electron collisions with trifluorides: BF3 and PF3 molecules.
AB  - Absolute total cross sections (TCSs) for electron scattering from boron
      trifluoride (BF(3)) and phosphorus trifluoride (PF(3)) molecules have been
      measured using a linear transmission method. The electron energy ranges from 0.6
      to 370 eV for BF(3) and from 0.5 to 370 eV for PF(3). The TCS energy dependence
      for BF(3) exhibits two very pronounced enhancements: resonantlike narrow feature
      located near 3.6 eV with the maximum value of 19.2 x 10(-20) m(2), and
      intermediate energy very broad enhancement with two humps, one centered around 21
      eV (18.8 x 10(-20) m(2) in the maximum) and the other near 45 eV (19.5 x 10(-20)
      m(2)). For PF(3) the TCS has quite different low-energy dependence: at 0.5 eV it
      has a high value of 70 x 10(-20) m(2) and decreases steeply towards higher
      energies. Beyond the minimum near 5.5 eV, the TCS reveals two distinct humps: the
      resonant one centered near 11 eV with the peak value of 32.9 x 10(-20) m(2) and
      the second one much broader around 35 eV (27.9 x 10(-20) m(2)). The present TCSs
      for trifluorides are compared to each other as well as to previous TCS data for
      selected perfluorides and to results for their perhydrided counterparts. The
      differences and similarities in the shape and magnitude of TCSs are pointed out.

PMID- 15260730
TI  - Photoassociation spectroscopy of ultracold Cs below the 6P1/2 limit.
AB  - We have performed high precision photoassociation spectroscopy of ultracold
      cesium gas. Using trap-loss fluorescence detection and controlling the background
      cesium pressure we were able to photoassociate atoms into excited states of
      ultracold molecules with large detunings up to 56 cm(-1) below the Cs(6S(1/2)) +
      Cs(6P(1/2)) atomic asymptote. Vibrational progressions are assigned to 0(g)(-),
      0(u)(+), and 1(g) long-range states. By fitting the spectral data to the LeRoy
      Bernstein expression, the effective coefficients of the leading long-range
      interactions and the vibrational quantum number at dissociation are obtained. In
      addition we have observed spectral perturbations between states of the same
      symmetry belonging to different asymptotes (6P(1/2) and 6P(3/2)). The
      perturbations are manifested through irregular vibrational level spacings and are
      especially pronounced in the 0(u)(+) symmetry. Many observed rotational levels
      indicate d- and higher partial wave contributions to the photoassociation cross
      section in the presence of trapping laser light, while spectral regions with only
      weak features suggest nodes in the lower state wave functions corresponding to
      the two ground state atoms asymptote.

PMID- 15260731
TI  - Quantum treatment of the Ar-HI photodissociation dynamics.
AB  - A wave packet simulation of the ultraviolet photolysis dynamics of Ar-HI(upsilon
      = 0) is reported. Cluster photodissociation is started from two different initial
      states, namely, the ground van der Waals (vdW) and the first excited vdW bending
      state, associated with the Ar-I-H and Ar-H-I isomeric forms of the system,
      respectively. Formation of Ar-I radical products is investigated over the energy
      range of the cluster absorption spectrum. It is found that the yield of bound Ar
      I radical complexes is typically 90%-100% and 70%-80% for the initial states
      associated with the Ar-I-H and Ar-H-I isomers, respectively. This result is in
      agreement with the experimentally observed time-of-flight spectrum of the
      hydrogen fragment produced after Ar-HI photodissociation. The high Ar-I yield is
      explained mainly by the small amount of energy available for the radical that is
      converted into internal energy in the photofragmentation process, which enhances
      the Ar-I survival probability. Quantum interference effects manifest themselves
      in structures in the angular distribution of the hydrogen fragment, and in
      pronounced rainbow patterns in the rotational distributions of the Ar-I radical.

PMID- 15260732
TI  - Franck-Condon simulation of the single-vibronic-level emission spectra of
      HPCl/DPCl and the chemiluminescence spectrum of HPCl, including anharmonicity.
AB  - Restricted-spin coupled-cluster single-double plus perturbative triple excitation
      [RCCSD(T)] potential energy functions (PEFs) were calculated for the X (2)A" and
      A (2)A' states of HPCl employing the augmented correlation-consistent polarized
      valence-quadruple-zeta (aug-cc-pVQZ) basis set. Further geometry optimization
      calculations were carried out on both electronic states of HPCl at the RCCSD(T)
      level with all electron and quasirelativistic effective core potential basis sets
      of better than the aug-cc-pVQZ quality, and also including some core electrons,
      in order to obtain more reliable geometrical parameters and relative electronic
      energy of the two states. Anharmonic vibrational wave functions of the two states
      of HPCl and DPCl, and Franck-Condon (FC) factors of the A (2)A'-X (2)A"
      transition were computed employing the RCCSD(T)/aug-cc-pVQZ PEFs. Calculated FC
      factors with allowance for Duschinsky rotation and anharmonicity were used to
      simulate the single-vibronic-level (SVL) emission spectra of HPCl and DPCl
      reported by Brandon et al. [J. Chem. Phys. 119, 2037 (2003)] and the
      chemiluminescence spectrum reported by Bramwell et al. [Chem. Phys. Lett. 331,
      483 (2000)]. Comparison between simulated and observed SVL emission spectra gives
      the experimentally derived equilibrium geometry of the A (2)A' state of HPCl of
      r(e)(PCl) = 2.0035 +/- 0.0015 A, theta(e) = 116.08 +/- 0.60 degrees, and r(e)(HP)
      = 1.4063+/-0.0015 A via the iterative Franck-Condon analysis procedure.
      Comparison between simulated and observed chemiluminescence spectra confirms that
      the vibrational population distribution of the A (2)A' state of HPCl is non
      Boltzmann, as proposed by Baraille et al. [Chem. Phys. 289, 263 (2003)].

PMID- 15260733
TI  - Calculation of the photodetachment cross sections of the HCN- and HNC- dipole
      bound anions as described by a one-electron Drude model.
AB  - The Drude model for treating the interaction of excess electrons with polar
      molecules is extended to calculate continuum functions and to evaluate
      photodetachment cross sections. The approach is applied to calculate the cross
      sections for photodetachment of dipole-bound electrons from HCN(-) and HNC(-). In
      addition, an adiabatic model separating the angular and radial degrees of freedom
      of the excess electron is introduced and shown to account in a qualitative manner
      for the cross sections.

PMID- 15260734
TI  - Dissociation of the ground state vinoxy radical and its photolytic precursor
      chloroacetaldehyde: electronic nonadiabaticity and the suppression of the
      H+ketene channel.
AB  - This work is a study of the competition between the two unimolecular reaction
      channels available to the vinoxy radical (CH(2)CHO), C-H fission to form
      H+ketene, and isomerization to the acetyl radical (CH(3)CO) followed by C-C
      fission to form CH(3) + CO. Chloroacetaldehyde (CH(2)ClCHO) was used as a
      photolytic precursor to the vinoxy radical in its ground state; photodissociation
      of chloroacetaldehyde at 193 nm produces vinoxy radicals with internal energies
      spanning the G3//B3LYP calculated barriers to the two available unimolecular
      reaction channels. The onset of the CH(3) + CO channel, via isomerization to the
      acetyl radical, was found to occur at an internal energy of 41 +/- 2 kcal/mol,
      agreeing well with our calculated isomerization barrier of 40.8 kcal/mol.
      Branching to the H+ketene channel was too small to be detected; we conclude that
      the branching to the H+ketene channel must be at least a factor of 200 lower than
      what is predicted by a RRKM analysis based on our electronic structure
      calculations. This dramatic result may be explained in part by the presence of a
      conical intersection at planar geometries along the reaction coordinate leading
      to H+ketene, which results in electronically nonadiabatic recrossing of the
      transition state.

PMID- 15260735
TI  - Formation of HXeO in a xenon matrix: indirect evidence of production, trapping,
      and mobility of XeO (1(1)Sigma+) in solid Xe.
AB  - IR spectroscopy, laser induced fluorescence (LIF), and thermoluminescence (TL)
      measurements have been combined to monitor trapping, thermal mobility, and
      reactions of oxygen atoms in solid xenon. HXeO and O(3) have been used as IR
      active species that probe the reactions of oxygen atoms. N(2)O and H(2)O have
      been used as precursors for oxygen atoms by photolysis at 193 nm. Upon annealing
      of matrices after photolysis, ozone forms at two different temperatures: at 18-24
      K from close O ...O(2) pairs and at approximately 27 K due to global mobility of
      oxygen atoms. HXeO forms at approximately 30 K reliably at higher temperature
      than ozone. Both LIF and TL show activation of oxygen atoms around 30 K.
      Irradiation at 240 nm after the photolysis at 193 nm depletes the oxygen atom
      emission at 750 nm and reduces the amount of HXeO generated in subsequent
      annealing. Part of the 750 nm emission can be regenerated by 266 nm and this
      process increases the yield of HXeO in annealing as well. Thus, we connect oxygen
      atoms emitting at 750 nm with annealing-induced formation of HXeO radicals. Ab
      initio calculations at the CCSD(T)/cc-pV5Z level show that XeO (1(1)Sigma(+)) is
      much more deeply bound [D(e) = 1.62 eV for XeO --> Xe+O((1)D)] than previous
      calculations have predicted. Taking into account the interactions with the medium
      in an approximate way, it is estimated that XeO (1(1)Sigma(+)) has a similar
      energy in solid xenon as compared with interstitially trapped O((3)P) suggesting
      that both possibly coexist in a low temperature solid. Taking into account the
      computational results and the behavior of HXeO and O(3) in annealing and
      irradiations, it is suggested that HXeO may be formed from singlet oxygen atoms
      which are trapped in a solid as XeO (1(1)Sigma(+)).

PMID- 15260736
TI  - Theoretical calculations of infrared absorption, vibrational circular dichroism,
      and two-dimensional vibrational spectra of acetylproline in liquids water and
      chloroform.
AB  - Infrared absorption, vibrational circular dichroism, and two-dimensional infrared
      pump-probe and photon echo spectra of acetylproline solutions are theoretically
      calculated and directly compared with experiments. In order to quantitatively
      determine interpeptide interaction-induced amide I mode frequency shifts, high
      level quantum chemistry calculations were performed. The solvatochromic amide I
      mode frequency shift and fluctuation were taken into account by carrying out
      molecular dynamics simulations of acetylproline dissolved in liquids water and
      chloroform and by using the extrapolation method developed recently. We first
      studied correlation time scales of the two amide I vibrational frequency
      fluctuations, cross correlation between the two fluctuating local mode
      frequencies, ensemble averaged conformations of the acetylproline molecule in
      liquids water and chloroform. The corresponding conformations of the
      acetylproline in liquids water and chloroform are close to the ideal 3(10) helix
      and the C(7) structure, respectively. A few methods proposed to determine the
      angle between the two transition dipoles associated with the amide I vibrations
      were tested and their limitations are discussed.

PMID- 15260737
TI  - Thermal conductivity, thermal effusivity, and specific heat capacity near the
      lower critical point of the binary liquid mixture n-butoxyethanol-water.
AB  - Experimental investigations on binary liquid mixtures near the critical mixing
      point are presently leading to a controversy about the anomaly in the thermal
      conductivity. A photopyroelectric technique is used to determine the thermal
      conductivity and the effusivity of the binary liquid mixture n-butoxyethanol
      water at its critical concentration near the critical mixing point. It is proven
      that, contrary to previous reports, there is no critical enhancement in the
      thermal conductivity. The specific heat capacity is calculated from these results
      and compared with the results from measurements performed by adiabatic scanning
      calorimetry.

PMID- 15260738
TI  - Theory of excluded volume equation of state: higher approximations and new
      generation of equations of state for entire density range.
AB  - A novel theory of an equation of state based on excluded volume and formulated in
      two preceding papers for gases and gaseous mixtures is extended to the entire
      density range by considering higher (beginning from the third) approximations of
      the theory. The algorithm of constructing higher approximations is elaborated.
      Equations of state are deduced using the requirement of maximum simplicity and
      contain a single free parameter to be chosen by reason of convenience or
      simplicity or to be used as a fitting parameter with respect to the computer
      simulation database. In this way, precise equations of state are derived for the
      hard-sphere fluid in the entire density range. On the side, the theory reproduces
      most known earlier equations of state for hard spheres and determines their place
      in the hierarchy of approximations. Equations of state for van der Waals fluids
      are also presented, and their critical parameters are estimated.

PMID- 15260739
TI  - Relationship between cohesive energy density and hydrophobicity.
AB  - It has been recently claimed that the large cohesive energy density of water is
      the ultimate cause of the poor solubility of nonpolar compounds in water. In
      order to test the validity of this idea, we analyze the difference in solubility
      between light water and heavy water of several nonpolar compounds. Even though
      the cohesive energy density of D(2)O is larger than that of H(2)O, nonpolar
      compounds are slightly more soluble in D(2)O than H(2)O. In such case
      experimental data do not support the correctness of the large cohesive energy
      density as the ultimate cause of hydrophobicity. We show that D(2)O is a slightly
      better solvent than H(2)O for nonpolar compounds because it is slightly less
      costly to create a cavity in the former liquid. This is because there is slightly
      more void volume in heavy water than in light water.

PMID- 15260740
TI  - Electronic structure of crystalline copper phthalocyanine.
AB  - The electronic structure of copper-phthalocyanine (CuPc) has been studied both
      experimentally and theoretically. Experiments have been performed on alpha and
      beta crystalline phases, using photoemission spectroscopy to probe core levels
      and valence band spectra. Different photon energies have been used, in order to
      probe different sample depths. Only minor differences have been observed in the
      experimental data on the two different phases, except for a small charge effect
      on the beta phase crystal. First-principles calculations have been performed
      using the density functional for molecular and three-dimensional periodic solids
      (Dmol(3)) code on both the single CuPc molecule and the beta phase, allowing the
      identification of the different atomic and angular contributions to the
      experimental density of states. In particular, the highest occupied molecular
      level is mainly due to Cu and N states. The comparison between theoretical data
      obtained for the CuPc in the beta phase and in the single molecule shows that the
      interchain interaction between the molecules is negligible, whereas slightly
      stronger intrachain interactions occur.

PMID- 15260741
TI  - Pores in bilayer membranes of amphiphilic molecules: coarse-grained molecular
      dynamics simulations compared with simple mesoscopic models.
AB  - We investigate pores in fluid membranes by molecular dynamics simulations of an
      amphiphile-solvent mixture, using a molecular coarse-grained model. The
      amphiphilic membranes self-assemble into a lamellar stack of amphiphilic bilayers
      separated by solvent layers. We focus on the particular case of tensionless
      membranes, in which pores spontaneously appear because of thermal fluctuations.
      Their spatial distribution is similar to that of a random set of repulsive hard
      disks. The size and shape distribution of individual pores can be described
      satisfactorily by a simple mesoscopic model, which accounts only for a pore
      independent core energy and a line tension penalty at the pore edges. In
      particular, the pores are not circular: their shapes are fractal and have the
      same characteristics as those of two-dimensional ring polymers. Finally, we study
      the size-fluctuation dynamics of the pores, and compare the time evolution of
      their contour length to a random walk in a linear potential.

PMID- 15260742
TI  - Scattering of O2 from AL111.
AB  - Experimental results are presented for the scattering of well-defined beams of
      molecular oxygen incident on clean Al(111). The data consist of scattered angular
      distributions measured as a function of incident angle, and for fixed incident
      angle, the dependence on surface temperature of the angular distributions. The
      measurements are interpreted in terms of a scattering theory that treats the
      exchange of energy between the translational and rotational motions of the
      molecule and the phonons of the surface using classical dynamics. The dependence
      of the measured angular distributions on incident beam angle and temperature is
      well explained by the theory. Rotational excitation and quantum excitation of the
      O(2) internal stretching mode are briefly discussed.

PMID- 15260743
TI  - Computer simulations of adsorption and diffusion for binary mixtures of methane
      and hydrogen in titanosilicates.
AB  - Equilibrium molecular dynamics (MD) simulations of equimolar mixtures of hydrogen
      and methane were performed in three different titanosilicates: naturally
      occurring zorite and two synthetic titanosilicates, ETS-4 and ETS-10. In
      addition, single-component MD simulations and adsorption isotherms generated
      using grand canonical Monte Carlo simulations were performed to support the
      mixture simulations. The goal of this study was to determine the best membrane
      material to carry out hydrogen/methane separations. ETS-10 has a three
      dimensional pore network. ETS-4 and zorite have two-dimensional pore networks.
      The simulations carried out in this study show that the increased porosity of ETS
      10 results in self-diffusion coefficients for both hydrogen and methane that are
      higher in ETS-10 than in either ETS-4 or zorite. Methane only showed appreciable
      displacement in ETS-10. The ability of the methane molecules to move in all three
      directions in ETS-10 was demonstrated by the high degree of isotropy shown in the
      values of the x, y, and z components of the self-diffusion coefficient for
      methane in ETS-10. From our simulations we conclude that ETS-10 would be better
      suited for fast industrial separations of hydrogen and methane. However, the
      separation would not result in a pure hydrogen stream. In contrast, ETS-4 and
      zorite would act as true molecular sieves for separations of hydrogen and
      methane, as the methane would not move through membranes made of these materials.
      This was indicated by the near-zero self-diffusion coefficient of methane in ETS
      4 and zorite.

PMID- 15260744
TI  - The density distributions of the counterions and the coions confined in two
      similarly charged plates.
AB  - By using the field-theoretic method, we established a unified systematic
      formulation of a model of counterions and coions confined in two similarly
      charged plates, and calculated the density distributions of counterions and
      coions with various coupling parameters by the two methods: Poisson-Boltzmann
      (PB) approach and the strong coupling (SC) theory, respectively. We also
      performed Monte Carlo simulations, and obtained the density distributions of
      counterions and coions with several different coupling parameters. Comparing our
      theoretical results with those from Monte Carlo simulation, we find that the PB
      approach is valid when the coupling parameter Xi is smaller than 1, but, as Xi >
      or = 1, the results by the PB approach deviate from the corresponding Monte Carlo
      simulation data, and the deviation gets larger with the coupling parameter
      increasing. This shows that the PB approach is completely invalid when the
      coupling parameter is equal to 1 or larger than 1. For the latter case, the
      development trend of the distribution curve calculated by SC theory agrees with
      that from Monte Carlo simulation as the coupling parameter increases. This
      demonstrates that the SC theory can give a qualitative available explanation on
      the density distribution of the counterions in the system in which the coupling
      parameters are strictly confined.

PMID- 15260745
TI  - Electric-field driven director oscillations in a nematic liquid crystal: a NMR
      investigation.
AB  - We have investigated the oscillatory behavior of the nematic director for 4
      pentyl-4'-cyanobiphenyl (5CB) when it is subjected to a static magnetic field and
      a sinusoidal electric field. In these experiments the two fields were inclined at
      about 50 degrees and the frequency of the electric field was varied from several
      hertz to approximately 1000 Hz. The director orientation was measured using time
      resolved deuterium NMR spectroscopy since this has the advantage of being able to
      determine the state of director alignment in the sample. In fact, for all of the
      frequencies studied the director is found to remain uniformly aligned. Since the
      diamagnetic and dielectric anisotropies are both positive the director oscillates
      in the plane formed by the two fields. These oscillations were observed to
      continue for many cycles, indicating that the coherence in the director
      orientation was not lost during this motion. The maximum and minimum angles made
      by the director with the magnetic field were determined, as a function of
      frequency, from the NMR spectrum averaged over many thousand cycles of the
      oscillations. At low frequencies (several hertz) these limiting angles are
      essentially independent of frequency but as the frequency increases the two
      angles approach each other and become equal at high frequencies, typically 1000
      Hz. Our results are well explained by a hydrodynamic theory in which the
      sinusoidal time dependence of the electric field is included in the torque
      balance equation. This analysis also shows that, for a range of frequencies
      between the high and low limits, these NMR experiments can give dynamic as well
      as static information concerning the nematic phase.

PMID- 15260746
TI  - Investigating the dominant corrections to the strong-stretching theory for dry
      polymeric brushes.
AB  - The accuracy of strong-stretching theory (SST) is examined against a detailed
      comparison to self-consistent field theory (SCFT) on dry polymeric brushes with
      thicknesses of up to approximately 17 times the natural chain extension. The
      comparison provides the strongest evidence to date that SST represents the exact
      thick-brush limit of SCFT. More importantly, it allows us to assess the
      effectiveness of proposed finite-stretching corrections to SST. Including the
      entropy of the free ends is shown to rectify the most severe inaccuracies in SST.
      The proximal layer proposed by Likhtman and Semenov provides another significant
      improvement, and we identify one further effect of similar importance for which
      there is not yet an accurate treatment. Furthermore, our study provides a
      valuable means of rejecting mistaken refinements to SST, and indeed one such
      example is revealed. A proper treatment of finite-stretching corrections is vital
      to a wide range of phenomena that depend on a small excess free energy, such as
      autophobic dewetting and the interaction between opposing brushes.

PMID- 15260747
TI  - Interactions between spherical colloids mediated by a liquid crystal: a molecular
      simulation and mesoscale study.
AB  - Monte Carlo simulations and dynamic field theory (DyFT) are used to study the
      interactions between dilute spherical particles, dispersed in nematic and
      isotropic phases of a liquid crystal. A recently developed simulation method
      (expanded ensemble density of states) was used to determine the potential of mean
      force (PMF) between the two spheres as a function of their separation and size.
      The PMF was also calculated by a dynamic field theory that describes the
      evolution of the local tensor order parameter. Both methods reveal an overall
      attraction between the colloids in the nematic phase; in the isotropic phase, the
      overall attraction between the colloids is much weaker, whereas the repulsion at
      short range is stronger. In addition, both methods predict a new topology of the
      disclination lines, which arises when the particles approach each other. The
      theory is found to describe the results of simulations remarkably well, down to
      length scales comparable to the size of the molecules. At separations
      corresponding to the width of individual molecular layers on the particles'
      surface, the two methods yield different defect structures. We attribute this
      difference to the neglect of density inhomogeneities in the DyFT. We also
      investigate the effects of the size of spherical colloids on their interactions.

PMID- 15260748
TI  - Effect of solvent quality on the conformations of a model comb polymer.
AB  - The effect of solvent quality on the equilibrium structure of a densely branched
      comb polymer is investigated based on the structure factor analyses by off
      lattice Monte Carlo simulations. First, theta temperature (theta(infinity)) must
      be determined to identify the solvent condition. We locate the characteristic
      temperature theta(A)(N) at which the second virial coefficient vanishes and the
      transition temperature theta(R)(N) at which radius of gyration R(g) of the chain
      varies most rapidly with temperature, i.e., d(2)R(g)/dT(2)|(theta(R)) = 0. N
      represents the total number of monomers of a comb. As N --> infinity, theta(A)
      and theta(R) coincide to a point that is identified as the true theta temperature
      (theta(infinity)). The structure factors of the main chain, the side chain, and
      the whole polymer are calculated, respectively. It is found that at T =
      theta(infinity), the structural factors S(qR(g)) for the overall comb polymers
      match quite well with those of their Gaussian counterparts. When T<
      theta(infinity), the overall comb polymer assumes collapsed conformations,
      similar to a homogeneous sphere. However, the structure factor of the side chain
      indicates that it always remains in an expanded state regardless of the solvent
      condition. It is attributed to the strong interactions between side chains. The
      same effect leads to enhanced rigidity of the main chain in comparison to the
      linear chain, as clearly observed from the rescaled Kratky plot.

PMID- 15260749
TI  - A computer simulation study of water drying at the interface of protein chains.
AB  - This study investigated the water drying (cavitation) in the interfacial region
      of two chains of a dimeric protein by nanosecond molecular dynamics simulations
      using explicit water representation. Separation-induced cavity of water was
      directly observed in the region. We evaluated the separation length scale of two
      chains on which the drying transition occurs, and the average number of water
      molecules that are expelled from the interfacial region during the transition.
      The obtained values can be rationalized by Kelvin equation for finite lateral
      size of confinement [K. Lum and A. Luzar, Phys. Rev. E 56, R6283 (1997)]. Also,
      we found that the drying transition is accompanied by an exponential reduction in
      the average hydrogen-bond number per interfacial water molecule. The results of
      this study may deepen the understanding of how hydrophobic interaction drives the
      assembly of protein chains.

PMID- 15260750
TI  - Protein and solvent dynamics: how strongly are they coupled?
AB  - Analysis of Raman and neutron scattering spectra of lysozyme demonstrates that
      the protein dynamics follow the dynamics of the solvents glycerol and trehalose
      over the entire temperature range measured 100-350 K. The protein's fast
      conformational fluctuations and low-frequency vibrations and their temperature
      variations are very sensitive to behavior of the solvents. Our results give
      insight into previous counterintuitive observations that protein relaxation is
      stronger in solid trehalose than in liquid glycerol. They also provide insight
      into the effectiveness of glycerol as a biological cryopreservant.

PMID- 15260751
TI  - Theory of dynamic barriers, activated hopping, and the glass transition in
      polymer melts.
AB  - A statistical mechanical theory of collective dynamic barriers, slow segmental
      relaxation, and the glass transition of polymer melts is developed by combining,
      and in some aspects extending, methods of mode coupling, density functional, and
      activated hopping transport theories. A coarse-grained description of polymer
      chains is adopted and the melt is treated as a liquid of segments. The theory is
      built on the idea that collective density fluctuations on length scales
      considerably longer than the local cage scale are of primary importance in the
      deeply supercooled regime. The barrier hopping or segmental relaxation time is
      predicted to be a function primarily of a single parameter that is chemical
      structure, temperature, and pressure dependent. This parameter depends on the
      material-specific dimensionless amplitude of thermal density fluctuations
      (compressibility) and a reduced segmental density determined by the packing
      length and backbone characteristic ratio. Analytic results are derived for a
      crossover temperature T(c), collective barrier, and glass transition temperature
      T(g). The relation of these quantities to structural and thermodynamic properties
      of the polymer melt is established. A universal power-law scaling behavior of the
      relaxation time below T(c) is predicted based on identification of a reduced
      temperature variable that quantifies the breadth of the supercooled regime.
      Connections between the ratio T(c)/T(g), two measures of dynamic fragility, and
      the magnitude of the local relaxation time at T(g) logically follow. Excellent
      agreement with experiment is found for these generic aspects, and the crucial
      importance of the experimentally observed near universality of the dynamic
      crossover time is established. Extensions of the theory to treat the full chain
      dynamics, heterogeneity, barrier fluctuations, and nonpolymeric thermal glass
      forming liquids are briefly discussed.

PMID- 15260752
TI  - Universal scaling, dynamic fragility, segmental relaxation, and vitrification in
      polymer melts.
AB  - Our theory of dynamic barriers, slow relaxation, and the glass transition of
      polymers melts is numerically applied using parameters relevant to real
      materials. The numerical results are found to be in qualitative agreement with
      all the approximate analytic expressions previously derived with quantitative
      differences on the order of approximately 20-30% or much less. The analytic
      prediction of a universal temperature dependence of the alpha relaxation time,
      and its intimate connection with the idea of a nearly universal crossover time,
      is established. Inter-relations between the breadth of the deeply supercooled
      regime, two definitions of the dynamic fragility, and the magnitude of the fast
      local Arrhenius process at the glass transition temperature are demonstrated and
      system-specific limitations identified. A quantitative application to segmental
      relaxation over 16 orders of magnitude in a polyvinylacetate melt yields
      encouraging results regarding the accuracy of the theory. The theoretical
      relaxation time results are well fit by multiple empirical forms (generally
      containing an assumed singular aspect) using parameters consistent with
      experimental studies. No physical significance is ascribed to this finding, but
      it does provide additional support for the temperature dependence of the alpha
      relaxation process predicted by the theory.

PMID- 15260753
TI  - Isomer abundance of small carbon clusters formed in buffer He gas.
AB  - We calculated the isomer spectrum of carbon clusters of 3-36 atoms, and performed
      molecular dynamics simulations of the cluster growth in buffer helium gas,
      showing that the isomers with potentials higher than those of the most stable
      clusters form with considerable probabilities under common experimental
      conditions.

PMID- 15260754
TI  - Bounds to average interelectronic angles in Hartree-Fock theory of atoms.
AB  - The average interelectronic <angle theta12> is the expectation value of the angle
      thetaij (0 < or = thetaij < or = pi) subtended by the position vectors ri and rj
      of a pair of electrons i and j. In the Hartree-Fock theory of atoms, we point out
      that the angle <theta12> and its subshell-pair components <theta12>nl,n'l' are
      bounded from above and below, where n and l are the principal and azimuthal
      quantum numbers. The upper bounds for <theta12>nl,n'l' with 0 < or = l, l' < or =
      3 are 9pi/16 (=101.25 degrees), 135pi/256 (approximately 94.922 degrees),
      265pi/512 (approximately 93.164 degrees), and 129pi/256 (approximately 90.703
      degrees) for sp, pd, df, and sf pairs, respectively, while they are pi/2 (=90
      degrees ) for the other ll' pairs, independent of n and n'. A weighted sum of
      these subshell-pair bounds gives an upper bound to <theta12>. The lower bounds
      are pi/2 in all the cases.

PMID- 15260755
TI  - Few-states models for three-photon absorption.
AB  - Few-states models are derived for the calculation of three-photon absorption
      matrix elements. Together with earlier derived few-states models for two-photon
      absorption, the models are evaluated against results from response theory
      calculations that provide the full sum-over-states values. It is demonstrated
      that not even for systems with charge-transfer character, where few-states models
      for two-photon absorption are in excellent agreement with response theory, do the
      models provide a quantitatively correct description for three-photon absorption.
      The convergence behavior, merits, and shortcomings of the models are elucidated
      in some detail. The role of various characteristics of the electronic structure,
      such as symmetry, charge transfer, and conjugation--important for the formation
      of a large three-photon cross section--is analyzed. As for two-photon absorption
      cross sections, it is essential to consider generalized few-states models also
      for three-photon absorption, that is, to account for dipolar directions and laser
      beam polarization. Despite their poor quantitative performance, it is argued that
      few-states models at times can be useful for interpretation purposes when applied
      to three-photon absorption.

PMID- 15260756
TI  - Conjugate-gradient optimization method for orbital-free density functional
      calculations.
AB  - Orbital-free density functional theory as an extension of traditional Thomas
      Fermi theory has attracted a lot of interest in the past decade because of
      developments in both more accurate kinetic energy functionals and highly
      efficient numerical methodology. In this paper, we developed a conjugate-gradient
      method for the numerical solution of spin-dependent extended Thomas-Fermi
      equation by incorporating techniques previously used in Kohn-Sham calculations.
      The key ingredient of the method is an approximate line-search scheme and a
      collective treatment of two spin densities in the case of spin-dependent extended
      Thomas-Fermi problem. Test calculations for a quartic two-dimensional quantum dot
      system and a three-dimensional sodium cluster Na216 with a local pseudopotential
      demonstrate that the method is accurate and efficient.

PMID- 15260757
TI  - Exact decoupling of the Dirac Hamiltonian. I. General theory.
AB  - Exact decoupling of positive- and negative-energy states in relativistic quantum
      chemistry is discussed in the framework of unitary transformation techniques. The
      obscure situation that each scheme of decoupling transformations relies on
      different, but very special parametrizations of the employed unitary matrices is
      critically analyzed. By applying the most general power series ansatz for the
      parametrization of the unitary matrices it is shown that all transformation
      protocols for decoupling the Dirac Hamiltonian have necessarily to start with an
      initial free-particle Foldy-Wouthuysen step. The purely numerical iteration
      scheme applying X-operator techniques to the Barysz-Sadlej-Snijders (BSS)
      Hamiltonian is compared to the analytical schemes of the Foldy-Wouthuysen (FW)
      and Douglas-Kroll-Hess (DKH) approaches. Relying on an illegal 1/c expansion of
      the Dirac Hamiltonian around the nonrelativistic limit, any higher-order FW
      transformation is in principle ill defined and doomed to fail, irrespective of
      the specific features of the external potential. It is shown that the DKH method
      is the only valid analytic unitary transformation scheme for the Dirac
      Hamiltonian. Its exact infinite-order version can be realized purely numerically
      by the BSS scheme, which is only able to yield matrix representations of the
      decoupled Hamiltonian but no analytic expressions for this operator. It is
      explained why a straightforward numerical iterative extension of the DKH
      procedure to arbitrary order employing matrix representations is not feasible
      within standard one-component electronic structure programs. A more sophisticated
      ansatz based on a symbolical evaluation of the DKH operators via a suitable
      parser routine is needed instead and introduced in Part II of this work.

PMID- 15260759
TI  - Classical trajectory calculations of intramolecular vibrational energy
      redistribution. I. Methanol-water complex.
AB  - Intramolecular vibrational energy redistributions of the O-H stretching (nuOH)
      vibration for the methanol monomer and its water complex, the methanol-water
      dimer, are investigated by using ab initio full-dimensional classical trajectory
      calculations. For the methanol monomer, in the high-energy regime of the 5nuOH
      overtone, the time dependence of the normal-mode energies indicates that energy
      flowed from the initial excited O-H stretching mode to the C-H stretching mode.
      This result confirms the experimental observation of energy redistribution
      between the O-H and C-H stretching vibrations [L. Lubich et al., Faraday Discuss.
      102, 167 (1995)]. Furthermore, a lot of dynamical information in the time domain
      is contained in the power spectra, whose density is given by the Fourier
      transformation of the total momentum obtained from trajectory calculations. For
      the methanol-water hydrogen-bonded complex, at the high-energy level of the 5nuOH
      overtone, the calculated power spectrum shows considerable splitting and
      broadening, indicating significant energy redistribution through strong coupling
      between the O-H stretching vibration and other vibrations. It is thus clear that
      the A-H...B hydrogen-bond formation facilitates energy redistribution subsequent
      to the vibrational excitation of the hydrogen-bonded A-H stretching mode.

PMID- 15260758
TI  - Thermal decomposition of peroxy acetyl nitrate CH3C(O)OONO2.
AB  - The thermal decomposition of peroxy acetyl nitrate (PAN) is investigated by low
      pressure flash thermolysis of PAN highly diluted in noble gases and subsequent
      isolation of the products in noble gas matrices at low temperatures and by
      density functional computations. The IR spectroscopically observed formation of
      CH3C(O)OO and H2CCO (ketene) besides NO2, CO2, and HOO implies a unimolecular
      decay pathway for the thermal decomposition of PAN. The major decomposition
      reaction of PAN is bond fission of the O-N single bond yielding the peroxy
      radical. The O-O bond fission pathway is a minor route. In the latter case the
      primary reaction products undergo secondary reactions whose products are
      spectroscopically identified. No evidence for rearrangement processes as the
      formation of methyl nitrate is observed. A detailed mapping of the reaction
      pathways for primary and secondary reactions using quantum chemical calculations
      is in good agreement with the experiment and predicts homolytic O-N and O-O bond
      fissions within the PAN molecule as the lowest energetic primary processes. In
      addition, the first IR spectroscopic characterization of two rotameric forms for
      the radical CH3C(O)OO is given.

PMID- 15260760
TI  - Classical trajectory calculations of intramolecular vibrational energy
      redistribution. II. Phenol-water complex.
AB  - Ab initio classical trajectory calculations have been applied to the
      intramolecular vibrational energy redistribution process of an O-H stretching
      vibration for phenol cation, [phenol]+, and its hydrogen-bonded water complex,
      [phenol-water]+. In phenol cation, a single narrow peak in the power spectrum,
      obtained by Fourier transformation of the autocorrelation function of its total
      momentum, indicates that the initial energy given to the O-H stretching
      oscillator of the phenol moiety is conserved and no energy flow occurs. On the
      other hand, for phenol-water cation, the calculated broadened power spectrum
      implies that the initial energy is not conserved and the energy flow causes an
      energy redistribution among various vibrational modes.

PMID- 15260761
TI  - Calculation of converged rovibrational energies and partition function for
      methane using vibrational-rotational configuration interaction.
AB  - The rovibration partition function of CH4 was calculated in the temperature range
      of 100-1000 K using well-converged energy levels that were calculated by
      vibrational-rotational configuration interaction using the Watson Hamiltonian for
      total angular momenta J = 0-50 and the MULTIMODE computer program. The
      configuration state functions are products of ground-state occupied and virtual
      modals obtained using the vibrational self-consistent field method. The Gilbert
      and Jordan potential energy surface was used for the calculations. The resulting
      partition function was used to test the harmonic oscillator approximation and the
      separable-rotation approximation. The harmonic oscillator, rigid-rotator
      approximation is in error by a factor of 2.3 at 300 K, but we also propose a
      separable-rotation approximation that is accurate within 2% from 100 to 1000 K.

PMID- 15260762
TI  - Isomeric interconversion in the linear Cl(-)-HD anion complex.
AB  - The rotationally resolved infrared photodissociation spectrum of Cl(-)-HD is
      measured in the HD stretch region. Two Sigma-Sigma bands are observed,
      corresponding to transitions from the ground state [the (nuHD = 0, n = 0) level]
      and first excited intermolecular bend state [the (nuHD = 0, n = 1) level]. The
      (nuHD = 0, n = 0) and (nuHD = 0, n = 1) states are predominantly associated with
      the linear Cl-...DH and Cl-...HD geometries, respectively. The spectrum is
      complicated by perturbative interactions between levels of the (nuHD = 0, n = 0)
      and (nuHD = 0, n = 1) rotational manifolds and between levels of the (nuHD = 1, n
      = 0) and (nuHD = 1, n = 1) rotational manifolds. A global fit to the transition
      frequencies, taking the lower and upper state perturbations into account, yields
      zero-order rotational and centrifugal distortion constants and allows us to
      establish that the (nuHD = 0, n = 1, J" = 0) level lies 13.7 cm(-1) above the
      (nuHD = 0, n = 0, J" = 0) level. Rovibrational energy level calculations
      performed using a recent ab initio potential energy surface confirm the picture
      emerging from the experimental data and provide good agreement with measured
      molecular parameters. The results emphasize the importance of quantum mechanical
      interconversion between two isomeric structures of a simple anion complex.

PMID- 15260763
TI  - Replacement equivalence of H- and argon in small (Ar)nH- clusters from optimized
      structure calculations.
AB  - The structural properties of some of the smaller ionic clusters of argon atoms
      containing the atomic impurity H-, ArnH- with n from 2 up to 7, are examined
      using different modeling for the interactions within each cluster and by
      employing different theoretical treatments, both classical and quantum, for the
      energetics. The same calculations are also carried out for the corresponding
      neutral homogeneous clusters Ar(n+1). The results of the calculations, the
      physical reliability of the interactions modeling, and the similarities and the
      difference between the anionic and the neutral complexes are discussed in some
      detail. The emerging picture shows that, due to specific features of the employed
      atom-atom potentials, the ArnH- and Ar(n+1) clusters present very similar
      structures, where the H- dopant substitutes for one of the outer Ar atoms but
      does not undergo as yet solvation within such small clusters.

PMID- 15260764
TI  - Excited state electronic structures and dynamics of NOCl: a new potential
      function set, absorption spectrum, and photodissociation mechanism.
AB  - A set of analytical potential energy surfaces (PESs) for six singlet excited
      states of NOCl are constructed based on multireference configuration interaction
      calculations. The total absorption cross section at the energy range of 2-7 eV is
      calculated by quantum dynamics calculations with the present PESs and transition
      dipole moments. The calculated absorption spectrum agrees well with the
      experiment. It is also found that the A band with the absorption maximum at 6.3
      eV is attributed to the transition to the 4 1A' state, though the excitations to
      the 3 1A' and 3 1A" states contribute to the spectrum at the energy range between
      4 and 5 eV. The spin-forbidden transitions are concluded to be negligibly weak.
      The mechanism of photodissociation reaction at the energy region corresponding to
      the A band is examined. The nonadiabatic transition rates from the 4 1A' state to
      lower singlet and triplet states are estimated by Fermi's golden rule, and the
      transitions to the 1 1A' and 3 1A' states induced by vibronic coupling are found
      to be the predominant dissociation pathways. The experimentally observed energy
      dependence of the recoil anisotropy of the fragments is discussed based on the
      calculated nonadiabatic transition rates.

PMID- 15260765
TI  - Preparation and resolution of molecular states by coherent sequences of phase
      locked ultrashort laser pulses.
AB  - We study the application of nonlinear wave packet interferometry to the
      preparation and resolution of the overlaps of nonstationary nuclear wave
      functions evolving in an excited electronic state of a diatomic molecule. It is
      shown that possible experiments with two phase-locked ultrashort pulsepairs can
      be used to determine a specific vibrational wave packet state in terms of
      coherent states of the ground electronic state. We apply this scheme to an
      idealized molecule with harmonic potential energy surfaces and to the X <-- B
      transition states of the iodine molecule. Our results indicate that this scheme
      is very promising as a potential tool to quantum control.

PMID- 15260766
TI  - First principles simulation of the UV absorption spectrum of ethylene using the
      vertical Franck-Condon approach.
AB  - A new method which we refer to as vertical Franck-Condon is proposed to calculate
      electronic absorption spectra of polyatomic molecules. In accord with the short
      time picture of spectroscopy, the excited-state potential energy surface is
      expanded at the ground-state equilibrium geometry and the focus of the approach
      is more on the overall shape of the spectrum and the positions of the band
      maxima, rather than the precise position of the 0-0 lines. The Born-Oppenheimer
      approximation and the separability of the excited-state potential energy surface
      along the excited-state normal mode coordinates are assumed. However, the
      potential surface is not necessarily approximated as harmonic oscillator
      potentials along the individual normal modes. Instead, depending upon the nature
      of the potential surface along a particular normal mode, it is treated either in
      the harmonic approximation or the full one-dimensional potential is considered
      along this mode. The vertical Franck-Condon approach is applicable therefore even
      in cases where the excited state potential energy surface is highly anharmonic
      and the conventional harmonic Franck-Condon approach is inadequate. As an
      application of the method, the ultraviolet spectrum of ethylene between 6.2 eV
      (50,000 cm(-1)) and 8.7 eV (70,000 cm(-1)) is simulated, using the Similarity
      Transformed Equation of Motion Coupled-Cluster method to describe the required
      features of the potential energy surfaces. The spectrum is shown to be a result
      of sharp doublet structures stemming from the pi --> 3s (Rydberg) state
      superimposed on top of a broad band resulting from the pi --> pi* (valence)
      state. For the Rydberg state, the symmetric C=C stretch and the torsion mode
      contribute to the spectrum, while the broad valence band results from excitation
      into the C=C stretch, CH2 scissors, and the torsion mode. For both states, the
      potential along the torsion mode is highly anharmonic and the full treatment of
      the potential along this mode in the vertical Franck-Condon method is required.

PMID- 15260767
TI  - High-resolution kinetic energy release distributions and dissociation energies
      for fullerene ions Cn+, 42 < or = n < or = 90.
AB  - We have measured the kinetic energy released in the unimolecular dissociation of
      fullerene ions, Cn+ --> C(n-2)+ + C2, for sizes 42 < or = n < or = 90. A three
      sector-field mass spectrometer equipped with two electric sectors has been used
      in order to ensure that contributions from isotopomers of different masses do not
      distort the experimental kinetic energy release distributions. We apply the
      concept of microcanonical temperature to derive from these data the dissociation
      energies of fullerene cations. They are converted to dissociation energies of
      neutral fullerenes with help of published adiabatic ionization energies. The
      results are compared with literature values.

PMID- 15260768
TI  - Density functional investigations of the properties and thermochemistry of UF6
      and UF5 using valence-electron and all-electron approaches.
AB  - The structural properties and thermochemistry of UF6 and UF5 have been
      investigated using both Hartree-Fock and density functional theory (DFT)
      approximations. Within the latter approach, the local spin-density approximation,
      the generalized gradient approximation, and hybrid density functionals were
      considered. To describe the uranium atom we employed small-core (60 electrons)
      and large-core (78 electrons) relativistic effective core potentials (RECPs), as
      well as the all-electron approximation based on the two-component third-order
      Douglas-Kroll-Hess Hamiltonian. For structural properties, we obtained very good
      agreement with experiment with DFT and both large and small-core RECPs. The best
      match with experiment is given by the hybrid functionals with the small-core
      RECP. The bond dissociation energy (BDE) was obtained from the relative energies
      of the fragments [UF6 --> UF5 + F], corrected for zero-point energy and spin
      orbit interaction. Very good agreement was found between the BDE obtained from
      all-electron calculations and those calculated with the small-core RECP, while
      those from the large-core RECP are off by more than 50%. In order to obtain good
      agreement with experiment in the BDE it is imperative to work with hybrid density
      functionals and a small-core RECP.

PMID- 15260769
TI  - The Xe shielding surfaces for Xe interacting with linear molecules and spherical
      tops.
AB  - The 129Xe nuclear magnetic resonance spectrum of xenon in gas mixtures of Xe with
      other molecules provides a test of the ab initio surfaces for the intermolecular
      shielding of Xe in the presence of the other molecule. We examine the electron
      correlation contributions to the Xe-CO2, Xe-N2, Xe-CO, Xe-CH4, and Xe-CF4
      shielding surfaces and test the calculations against the experimental temperature
      dependence of the density coefficients of the Xe chemical shift in the gas
      mixtures at infinite dilution in Xe. Comparisons with the gas phase data permit
      the refinement of site-site potential functions for Xe-N2, Xe-CO, and Xe-CF4
      especially for atom-Xe distances in the range 3.5-6 A. With the atom-atom
      shielding surfaces and potential parameters obtained in the present work,
      construction of shielding surfaces and potentials for applications such as
      molecular dynamics averaging of Xe chemical shifts in liquid solvents containing
      CH3, CH2, CF3, and CF2 groups is possible.

PMID- 15260770
TI  - Vibrational and rotational dynamics of cyanoferrates in solution.
AB  - Ultrafast infrared spectroscopy has been used to measure vibrational energy
      relaxation (VER) and reorientation (Tr) times for the high frequency vibrational
      bands of potassium ferrocyanide and ferricyanide (CN stretches), and sodium
      nitroprusside (SNP, CN, and NO stretches) in water and several other solvents.
      Relatively short VER times (4-43 ps) are determined for the hexacyano species and
      for the NO band of SNP, but the CN band of SNP relaxes much more slowly (55-365
      ps). The solvent dependence of the VER times is similar for all the solutes and
      resembles what has been previously observed for triatomic molecular ions [Li et
      al., J. Chem. Phys. 98, 5499 (1993)]. Anisotropy decay times are also measured
      from the polarization dependence of the transient absorptions. The Tr times
      determined for SNP are different for the different vibrational bands; for the
      nondegenerate NO mode of nitroprusside (SNP) they are much longer (>15 ps),
      correlate with solvent viscosity, and are attributed to overall molecular
      rotation. The short Tr (<10 ps) times for the CN band in SNP and for the
      hexacyanoferrates are due to dipole orientational relaxation in which the
      transition moment rapidly redistributes among the degenerate modes. There is no
      evidence of intramolecular vibrational relaxation (IVR) to other high frequency
      modes. VER times measured for hexacarbonyls and SNP in methanol are similar,
      which suggests that the generally faster VER for the latter is in part because
      they are soluble in more strongly interacting polar solvents. The results are
      compared to those for small ions and metal carbonyls and are discussed in terms
      of the importance of solute charge and symmetry on VER.

PMID- 15260771
TI  - Phase behavior of n-alkanes in supercritical solution: a Monte Carlo study.
AB  - We present a coarse-grained model for n-alkanes in a supercritical solution,
      which is exemplified by a mixture of hexadecane and CO2. For pure hexadecane, the
      Monte Carlo simulations of the coarse-grained model reproduce the experimental
      phase diagram and the interfacial tension with good accuracy. For the mixture,
      the phase behavior sensitively depends on the compatibility of the polymer with
      the solvent. We present a global phase diagram with critical lines, which is in
      semiquantitative agreement with experiments. In this context we developed two
      computational schemes: The first adopts Wang-Landau sampling to the off-lattice
      grand canonical ensemble, the second combines umbrella sampling with an
      extrapolation scheme to determine the weight function. Additionally, we use
      Wertheim's theory (TPT1) to obtain the equation of state for our coarse-grained
      model of supercritical mixtures and discuss the behavior for longer alkanes.

PMID- 15260772
TI  - A Kirkwood-Buff derived force field for the simulation of aqueous guanidinium
      chloride solutions.
AB  - A force field for the simulation of aqueous guanidinium chloride solutions is
      presented. The force field was parametrized to reproduce the experimental density
      and Kirkwood-Buff integrals as a function of composition. Consequently, a
      reasonable description of the salt activity is obtained. The model also performs
      well for other properties such as the relative permittivity and enthalpy of
      mixing.

PMID- 15260773
TI  - Coupled reference interaction site model/simulation approach for thermochemistry
      of solvation: theory and prospects.
AB  - We present a new methodology for computing solvation free energy, which is based
      upon the reference interaction site model (RISM)/hypernetted chain (HNC)
      solvation free energy expression, but which substitutes radial distribution
      functions taken from simulations for those calculated by simultaneous solution of
      the RISM and HNC equations. Consequently, solvation free energy can be obtained
      from a single molecular dynamics or Monte Carlo simulation. Here we describe in
      detail the coupled RISM/simulation approach, and offer some error analysis.
      Finally we give the results of its application to a set of small test molecules
      in aqueous solution. The success shown in some of our results demonstrates that
      the coupled RISM/simulation approach is worth considering further as a
      potentially useful tool in studies of solvated systems, such as aqueous molecular
      biosystems.

PMID- 15260774
TI  - Theoretical calculations of effective exchange integrals by spin projected and
      unprojected broken-symmetry methods. III. Cluster models of three-dimensional
      KNiF3 solid.
AB  - Previously, we have performed the spin-polarized hybrid-density functional theory
      (HUDFT) calculations for elucidating magnetic properties of the two-dimensional
      (2D) K2NiF4 and K2CuF4 solids. In Part I, it has been concluded that the half-and
      half-(HH-) type HUDFT method is one of the best calculation methods for these
      species. On the other hand, in Part II, we have demonstrated that potential
      curves for cluster models of K2CuF4 and KCuF3 are reasonably calculated by the HH
      type HUDFT method under the approximate spin projection, and the lattice
      distortion resulted by Jahn-Teller effect is expressed as the second-order
      polynomial. In this study, we pay attention to the three-dimensional (3D)
      magnetic interactions in KNiF3. Our effective exchange integral Jab schemes for
      3D cluster models such as KNi8F12 (4) with and without point charges have
      provided the reasonable Jab values (-30.24-34.48 cm(-1)), in comparison with the
      experimental one (-30.58 cm(-1)). The 3D magnetic interactions have been
      investigated from viewpoints of the Mulliken spin density and charge density
      populations, the natural orbital analysis, and chemical indices. Point charges
      located in positions of fluorine anion adjacent to cluster model have reproduced
      Jab values well. Roles of potassium as counter cation in KNiF3 solid were also
      investigated. It was concluded that potassium has a role of stabilizing the 3D
      magnetic structures. Finally, the mutual relationships between broken-symmetry
      and symmetry-adapted approaches are discussed on the basis of chemical indices.

PMID- 15260775
TI  - Photodissociation of diiodomethane in acetonitrile solution and fragment
      recombination into iso-diiodomethane studied with ab initio molecular dynamics
      simulations.
AB  - Photodissociation of diiodomethane (CH2I2) in acetonitrile solution has been
      studied with ab initio molecular dynamics simulations, which show how the iso
      diiodomethane photoproduct (CH2I-I) can be formed. The first excited state,
      described by the "restricted open-shell Kohn-Sham" density functional method, is
      dissociative and photoexcitation of diiodomethane induces a breaking of one of
      the C-I bonds. In the simulations, we observe that energy dissipation to the
      surrounding solvent is essential in the formation of a stable iso-diiodomethane
      molecule. The caging effect of the solvent results in a recombination of the CH2I
      and I fragments into iso-diiodomethane on a picosecond time scale. The molecular
      dynamics simulations enable us to study the cage effect as well as the relaxation
      of intermediates and the distribution of energy. The CH2I fragment is formed
      vibrationally excited along the C-I stretching mode. After recombination of the
      CH2I and I fragments, iso-diiodomethane shows a strong vibration excitation in
      the CH2 group, which could be used as a fingerprint of the proposed mechanism.

PMID- 15260776
TI  - Nuclear and electron spin relaxation in paramagnetic complexes in solution:
      effects of the quantum nature of molecular vibrations.
AB  - A model of the paramagnetic relaxation enhancement is developed in terms of
      electron-spin relaxation caused by the zero-field splitting (ZFS) fluctuating in
      time due to a coupling between the electron-spin variables and quantum
      vibrations. The ZFS interaction provides a coupling between the electron-spin
      variables and vibrational degrees of freedom, and is represented as a Taylor
      series expansion in a set of vibrational modes (normal coordinates). A two-level
      harmonic oscillator subsystem is assumed, and the electron-spin relaxation
      associated with T2V and T1V vibrational relaxation is considered. The description
      of vibrationally induced electron-spin dynamics is incorporated into the
      calculations of the paramagnetic relaxation enhancement by the Solomon
      Bloembergen-Morgan approach as well as in the framework of the general slow
      motion theory. The theoretical predictions are compared with the experimental
      paramagnetic relaxation enhancement values for the Ni(H2O)6(2+) complex in
      aqueous solution. The parameters required by the model are obtained from quantum
      chemical and molecular dynamics studies. Comparison is made between the current
      model and its recently published classical counterpart.

PMID- 15260777
TI  - Optical linear response function with linear and diagonal quadratic electron
      vibration coupling in mixed quantum-classical systems.
AB  - Optical linear response function of linearly and quadratically coupled mixed
      quantum-classical condensed phase systems is derived. The linear response
      function is derived using Kapral's formalism of statistical mechanics in mixed
      quantum-classical systems. Our mixed quantum-classical linear dipole moment
      correlation function J(t) is compared with the full quantum J(t) [Y. J. Yan and
      S. Mukamel, J. Chem. Phys. 85, 5908 (1986)] in the high temperature limit. Model
      calculations and discussion of our results are presented. Various formulas of
      Franck-Condon factors for both linear and quadratic coupling are discussed.

PMID- 15260778
TI  - The role of intermolecular polarization for the stability of lithium
      intercalation compounds of alpha- and beta-perylene.
AB  - Lithium intercalation compounds of alpha- and beta-perylene are investigated by
      photoelectron spectroscopy. Spectroscopic data together with a Born-Haber cycle
      provide information on the formation enthalpy of those materials. This approach
      allows understanding the amount of charge transferred from the alkali metal atoms
      to the pi system, and illuminates the role of molecular versus solid-state
      properties in the formation of the intercalation compounds. In the bulk of alpha
      perylene material, molecular dimerization survives upon intercalation which
      reduces the Madelung energy of the intercalation compound but increases the
      electron-accepting capability of the organic system and facilitates the
      ionization of lithium atoms in the molecular solid environment. The lower
      ionization potential results in a larger charge transfer (about two electrons per
      molecule) in alpha-perylene compared to the monomeric system, beta-perylene.

PMID- 15260779
TI  - Dewetting at soft viscoelastic interfaces.
AB  - The dewetting transition of thin liquid films (approximately 100 nm) at soft
      viscoelastic interfaces is analyzed theoretically. It is shown that viscoelastic
      losses in the soft material can drastically increase the time to complete the
      dewetting. Thus, the influence of the thinning of the liquid film, due to the
      hydrodynamic drainage caused by the external applied pressure, has to be
      considered too. The squeezing pressure coupled with the hydrodynamic drainage may
      slow down the dewetting to almost zero growth rate of the dry zone; in this case
      a trapped rim of fluid should be observed.

PMID- 15260780
TI  - Photodissociation of ICN at the liquid/vapor interface of water.
AB  - The photodissociation of ICN adsorbed at the liquid/vapor interface of water is
      studied using classical molecular dynamics with nonadiabatic surface hopping. The
      cage escape, geminate recombination to form ICN and INC and the subsequent
      vibrational relaxation of these two molecules (on their ground electronic states)
      is compared with the same process in bulk water and with previous
      photodissociation studies at liquid interfaces. We find that the reduced surface
      density and weaker solvent-solute interactions give rise to reduced rate of
      nonadiabatic transitions and that the probability for cage escape at the
      interface is significantly enhanced due to the possibility that one or both of
      the photodissociation fragments desorb into the gas phase. The overall desorption
      probability varies from 75% to 92% for ICN initially located just below the Gibbs
      surface (50% bulk density) to ICN located just above the Gibbs surface,
      respectively. The corresponding geminate recombination probabilities are 18% and
      9%, respectively. The vibrational relaxation rate of the recombined ICN is slower
      than in the bulk by a factor of 2.3.

PMID- 15260781
TI  - A SPR and AFM study of the effect of surface heterogeneity on adsorption of
      proteins.
AB  - The effect of chemical heterogeneity of surfaces on the adsorption of proteins
      was investigated using model surfaces prepared by self-assembly of omega
      functionalized alkanethiols on gold substrates. Surface plasmon resonance was
      used to monitor the adsorption kinetics of bovine serum albumin (BSA) and the
      morphology of the adsorbed BSA was imaged with tapping mode atomic force
      microscopy. The experiments show that the morphology of the adsorbed protein
      layer was altered significantly only when the surface heterogeneity was
      distributed in a patchwise manner on a nanometer length scale, which is
      commensurate with the dimension of the protein. In contrast to linear flexible
      polymers where the initial adsorption rate remained unchanged upon introduction
      of the chemical heterogeneity, the initial rate for the globular protein changed
      from the value observed on homogeneous surfaces and was dependent on the
      heterogeneous distribution of the chemical sites.

PMID- 15260782
TI  - Growth kinetics, structure, and morphology of para-quaterphenyl thin films on
      gold(111).
AB  - The adsorption, desorption, and growth kinetics as well as the thin film
      morphology and crystal structure of p-quaterphenyl (4P) grown under ultrahigh
      vacuum conditions on single crystalline Au(111) have been investigated. Thermal
      desorption spectroscopy (TDS) reveals two distinct first-order peaks attributed
      to monolayer desorption followed by a zero-order multilayer desorption. The
      saturation coverage of the full 4P monolayer has been quantitatively measured
      with a quartz microbalance to be 8 x 10(13) molecules/cm2. Using low energy
      electron diffraction the structures of the 0.5 and 1 ML (monolayer) adsorbates
      have been studied, showing highly regular arrangements of the 4P molecules, which
      are affected by the (111) surface structure. At the transition from 0.5 to 1 ML a
      structural compression of the overlayer has been observed. The behavior of
      thicker 4P films has been investigated by combined TDS-XPS (XPS-x-ray
      photoelectron spectroscopy). A temperature-induced recrystallization process at
      about 270 K has been observed for a 7 nm thick 4P film grown at 93 K,
      corresponding to a transition from a disordered layerlike growth to a crystalline
      island growth. Ex situ optical microscopy and atomic-force microscopy
      investigations have revealed needle-shaped 4P islands. Applying x-ray diffraction
      the crystalline order and epitaxial relationship of the 4P films with 30 nm and
      200 nm mean thicknesses have been determined.

PMID- 15260783
TI  - Vibrational effects in laser-driven molecular wires.
AB  - The influence of an electron-vibrational coupling on the laser control of
      electron transport through a molecular wire that is attached to several
      electronic leads is investigated. These molecular vibrational modes induce an
      effective electron-electron interaction. In the regime where the wire electrons
      couple weakly to both the external leads and the vibrational modes, we derive
      within a Hartree-Fock approximation a nonlinear set of quantum kinetic equations.
      The quantum kinetic theory is then used to evaluate the laser driven, time
      averaged electron current through the wire-leads contacts. This formalism is
      applied to two archetypical situations in the presence of electron-vibrational
      effects, namely, (i) the generation of a ratchet or pump current in a symmetrical
      molecule by a harmonic mixing field and (ii) the laser switching of the current
      through the molecule.

PMID- 15260784
TI  - Structure prediction of high-pressure phases for alkali metal sulfides.
AB  - For a given chemical system we present a systematic approach to predict
      structures, which may exist at high pressure, by investigating the global
      enthalpy landscape. We combine global optimizations, based on empirical potential
      energy functions, and local optimizations (volume, cell shape, and atomic
      positions) on both Hartree-Fock and density functional theory level. We predict
      the existence of high-pressure phases for the alkali metal sulfides of the
      composition M2S (M = Li, Na, K, Rb, Cs), together with the transition pressures
      among these phases.

PMID- 15260785
TI  - Motion of spheres along a fluid-gas interface.
AB  - A system of many spherical particles, suspended in a quiescent fluid and touching
      a planar free fluid-gas interface, is considered. Stick fluid boundary conditions
      at the sphere surfaces are assumed. The free surface boundary conditions are
      taken into account with the use of the method of images. For such a quasi-two
      dimensional system, the one-sphere resistance operator is calculated numerically.
      Moreover, the corresponding friction and mobility tensors are constructed from
      irreducible multipole expansion. Finally, the long-distance terms of the two
      sphere mobility tensor are evaluated explicitly up to the order of 1/r3, where r
      is the interparticle distance. Experiments which have motivated this work are
      outlined.

PMID- 15260786
TI  - Atomistic mechanisms for the (1 x 1) <==> hex surface phase transformations of
      Pt(100).
AB  - The atomistic mechanisms and dynamics of the (1 x 1) --> hex surface
      reconstruction of the clean Pt(100) and its lifting upon CO adsorption have been
      studied by means of both density functional theory and molecular dynamics
      simulations based on the modified embedded-atom method. It was found that during
      the surface reconstruction from the square (1 x 1) to the approximately 20% more
      dense (quasi)hexagonal phase, the required extra atoms are extracted from the
      second layer, leaving highly mobile subsurface vacancies, even in the presence of
      adatom islands or steps. These vacancies will, by surface diffusion, coalesce to
      form steps. In contrast, during the reverse process--where the hex surface
      reconstruction is lifted upon adsorption of CO--the roughly 20% excess surface
      atoms are in a collective manner ejected to form chains of adatoms. In turn,
      these adatoms coalesce into islands and steps by surface diffusion. A result of
      the two totally different mechanisms is that the reconstruction process can be
      concluded not to be the reverse of the deconstruction process.

PMID- 15260787
TI  - Ab initio study of small graphitic cones with triangle, square, and pentagon
      apex.
AB  - Accurate geometries of carbon nanocones of different sizes with a triangle,
      square or pentagon at the apex have been determined for the first time using a
      quantum chemical optimization method. The structure close to the apex is
      distorted from an ideal conical surface. The charging effect of the central
      defect is quite different from that predicted by tight-binding calculations. The
      symmetry behavior of the frontier orbitals and the size of the highest occupied
      molecular orbital-lowest unoccupied molecular orbital gap versus cone type and
      size is explained. The density of states quickly converges towards that of
      graphite when the size of the cone increases. In comparison to previous results
      in the literature it is found that the local densities of states of cones, that
      are locally different but belong to the same topo-combinatoric class, share
      common features.

PMID- 15260788
TI  - Spectroscopic study of J aggregates of amphiphilic merocyanine dyes formed in
      their pure Langmuir films.
AB  - It is known that an amphiphilic merocyanine dye, 3-carboxymethyl-5-[2-(3
      octadecyl-2(3H)- benzothiazolylidene)ethylidene]-2-thioxo-4-thiazolidinone (DS)
      and its derivatives DSe and 6MeDS form J aggregates under the presence of
      metallic cations, although the dyes' static dipole moments must be favorable for
      H aggregates. A metal-free J aggregate of 6MeDS has been generated in its pure
      Langmuir films and transferred onto CaF2 substrates to investigate the molecular
      environment around the carboxylic group born by the dye. Combining visible and
      infrared spectroscopy, geometrical consideration based on ab initio calculations,
      and simulation of the excitation energy, a structural model of this J aggregate
      has been proposed. With this model, formation of intermolecular carboxyl-keto
      hydrogen bonds, which can compensate the electrostatic disadvantage of the J
      aggregate under the presence of water, has been suggested. As for another
      derivative of DS, DO, similar discussion has been made for its Mg2+ -containing J
      aggregate, which is found in this work. In addition, the proposed structural
      model can tell the cause of the difference in the tendency to J aggregate among
      6MeDS, DSe, DS, and DO.

PMID- 15260789
TI  - Li intercalation in TiO2 anatase: Raman spectroscopy and lattice dynamic studies.
AB  - Raman spectra of the electrochemically lithiated TiO2 anatase are reported. They
      evidence spectral features induced by Li intercalation in the high-frequency
      region. Emergence of these lines supports recent hypothesis [M. Wagemaker et al.,
      J. Am. Chem. Sec. 125, 840 (2003)] for formation of short Li-O valence bonds.
      This suggestion is verified by the lattice dynamics simulation based on the
      potential model with Li-O force constants extrapolated from known studies of the
      lithium oxide compounds. The obtained results confirm assumption of multiple Li
      positions and provide assignment of all the observed spectral features.

PMID- 15260790
TI  - The essential role of H-F substitution in the electron-phonon interactions and
      electron transfer in the negatively charged acenes.
AB  - The single charge transfer through acenes, partially H-F substituted acenes, and
      fluoroacenes is discussed. The reorganization energies between the neutral
      molecules and the corresponding monoanions for partially H-F substituted acenes
      lie between those for acenes and fluoroacenes. The delocalization of the lowest
      unoccupied molecular orbitals (LUMO) by substituting hydrogen atoms by fluorine
      atoms with the highest electronegativity in every element is the main reason why
      the reorganization energy between the neutral molecule and the monoanion for
      partially H-F substituted acenes lies between those for acenes and fluoroacenes.
      This result implies that the negatively charged partially H-F substituted acenes
      would be better conductors with rapid electron transfer than the negatively
      charged fluoroacenes if we assume that the overlap of the LUMO between partially
      H-F substituted acenes is not significantly different from that between two
      neighboring fluoroacenes. The structures of the monoanions of acenes,
      fluoroacenes, and partially H-F substituted acenes are optimized under D2h
      geometry, and the Jahn-Teller effects in the monoanions of benzene and
      fluorobenzene are discussed. The vibration effect onto the charge transfer
      problem is also discussed. The C-C stretching modes around 1500 cm(-1) are the
      main modes converting the neutral molecules to the monoanions in acenes,
      fluoroacenes, and partially H-F substituted acenes. It can be confirmed from the
      calculational results that the C-C stretching modes around 1500 cm(-1) the most
      strongly couple to the LUMO in these molecules. The main reason why the total
      electron-phonon coupling constants (lLUMO) for the monoanions of acenes in which
      four outer hydrogen atoms are substituted by fluorine atoms are larger than those
      for the monoanions of acenes in which several inner hydrogen atoms are
      substituted by fluorine atoms is suggested. The relationships between the
      electron transfer and the electron-phonon interactions are discussed. The plot of
      the reorganization energies against the lLUMO values is found to be nearly
      linear. In view of these results, the relationships between the normal and
      superconducting states are briefly discussed.

PMID- 15260791
TI  - Polyelectrolyte shells of copolymer micelles in aqueous solutions: a Monte Carlo
      study.
AB  - Multimolecular micelles, formed by polystyrene-block-poly(methacrylic acid) in
      water, are studied by lattice Monte Carlo method. Electrostatic interactions are
      calculated in the mean-field approximation by solving the Poisson-Boltzmann
      equation. The model is parametrized according to available experimental data. The
      dependence of micellar size on pH and ionic strength is calculated and compared
      with experimental data. A special attention is devoted to the behavior in
      solutions with a low ionic strength.

PMID- 15260792
TI  - High frequency acoustic excitations in ordered diblock copolymer studied by
      inelastic x-ray scattering.
AB  - The phonon propagation in lamellar nanostructures formed via self-assembling of
      short styrene-b-isoprene (SI) as well as of its more incompatible styrene-b
      (ethylene-alt-propylene) (SEP) counterpart was studied by inelastic x-ray
      scattering. Irrespective of the physical state of the block copolymers, a single
      acoustic phonon was observed in SI (ordered and disordered) and SEP (ordered). At
      GHz frequencies, inelastic light scattering from the same samples revealed very
      small dispersion in the sound phase velocity but a short phonon lifetime.

PMID- 15260793
TI  - The evolution dynamics of model proteins.
AB  - Explicit simulations of protein evolution, where protein chains are described at
      a molecular, although simplified, level provide important information to
      understand the similarities found to exist between known proteins. The results of
      such simulations suggest that a number of evolutionary-related quantities, such
      as the distribution of sequence similarity for structurally similar proteins, are
      controlled by evolutionary kinetics and do not reflect an equilibrium state. An
      important result for phylogeny is that a subset of the residues of each protein
      evolve on a much larger time scale than the other residues.

PMID- 15260794
TI  - Thermodynamics of soft anisotropic contact lines.
AB  - Contact lines arising from the intersection of interfaces between liquids and
      nematic liquid crystals are representative models of soft anisotropic contact
      lines. This paper presents the thermodynamics of soft anisotropic contact lines
      and the derivation of the one dimensional (1D) Gibbs-Duhem adsorption equation.
      Consistency between the 1D Gibbs-Duhem equation and the classical equations of
      lineal nematostatics is shown. Using a phase space that takes into account
      thermodynamics, liquid crystalline order, and geometric variables, the
      generalized nematic line Gibbs-Duhem equation reveals the presence of couplings
      between curvature, torsion, adsorption, temperature, and average molecular
      orientation. Merging the thermodynamic analysis with nematostatics results in a
      model for contact line shape and orientation selection. The ability of an
      adsorbed solute to orient the director and to bend and twist the contact line is
      predicted. The thermodynamic origin of preferred orientation at a straight
      contact line is established.

PMID- 15260795
TI  - Comparison of molecular dynamics with hybrid continuum-molecular dynamics for a
      single tethered polymer in a solvent.
AB  - We compare a newly developed hybrid simulation method which combines classical
      molecular dynamics (MD) and computational fluid dynamics (CFD) to a simulation
      consisting only of molecular dynamics. The hybrid code is composed of three
      regions: a classical MD region, a continuum domain where the dynamical equations
      are solved by standard CFD methods, and an overlap domain where transport
      information from the other two domains is exchanged. The exchange of information
      in the overlap region ensures that momentum, energy, and mass are conserved. The
      validity of the hybrid code is demonstrated by studying a single polymer tethered
      to a hard wall immersed in explicit solvent and undergoing shear flow. In
      classical molecular dynamics simulation a great deal of computational time is
      devoted to simulating solvent molecules, although the solvent itself is of no
      direct interest. By contrast, the hybrid code simulates the polymer and
      surrounding solvent explicitly, whereas the solvent farther away from the polymer
      is modeled using a continuum description. In the hybrid simulations the MD domain
      is an open system whose number of particles is controlled to filter the
      perturbative density waves produced by the polymer motion. We compare
      conformational properties of the polymer in both simulations for various shear
      rates. In all cases polymer properties compare extremely well between the two
      simulation scenarios, thereby demonstrating that this hybrid method is a useful
      way to model a system with polymers and under nonzero flow conditions. There is
      also good agreement between the MD and hybrid schemes and experimental data on
      tethered DNA in flow. The computational cost of the hybrid protocol can be
      reduced to less than 6% of the cost of updating the MD forces, confirming the
      practical value of the method.

PMID- 15260796
TI  - Interplay of secondary structures and side-chain contacts in the denatured state
      of BBA1.
AB  - The denatured state of a miniprotein BBA1 is studied under the native condition
      with the AMBER/Poisson-Boltzmann energy model and with the self-guided enhanced
      sampling technique. Forty independent trajectories are collected to sample the
      highly diversified denatured structures. Our simulation data show that the
      denatured BBA1 contains high percentage of native helix and native turn, but low
      percentage of native hairpin. Conditional population analysis indicates that the
      native helix formation and the native hairpin formation are not cooperative in
      the denatured state. Side-chain analysis shows that the native hydrophobic
      contacts are more preferred than the non-native hydrophobic contacts in the
      denatured BBA1. In contrast, the salt-bridge contacts are more or less
      nonspecific even if their populations are higher than those of hydrophobic
      contacts. Analysis of the trajectories shows that the native helix mostly
      initiates near the N terminus and propagates to the C terminus, and mostly forms
      from 3(10)-helix/turn to alpha helix. The same analysis shows that the native
      turn is important but not necessary in its formation in the denatured BBA1. In
      addition, the formations of the two strands in the native hairpin are rather
      asymmetric, demonstrating the likely influence of the protein environment.
      Energetic analysis shows that the native helix formation is largely driven by
      electrostatic interactions in denatured BBA1. Further, the native helix formation
      is associated with the breakup of non-native salt-bridge contacts and the
      accumulation of native salt-bridge contacts. However, the native hydrophobic
      contacts only show a small increase upon the native helix formation while the non
      native hydrophobic contacts stay essentially the same, different from the
      evolution of hydrophobic contacts observed in an isolated helix folding.

PMID- 15260797
TI  - Free volume properties of a linear soft polymer: a computer simulation study.
AB  - Molecular dynamics simulation of a linear soft polymer has been performed and the
      free volume properties of the system have been analyzed in detail in terms of the
      Voronoi polyhedra of the monomers. It is found that there are only small density
      fluctuations present in the system. The local environment of the monomers is
      found to be rather spherical, even in comparison with liquids of atoms or small
      molecules. The monomers are found to be, on average, eight coordinated by their
      nearest geometric neighbors, including intra-chain and inter-chain ones. The
      packing of the monomers is found to be rather compact, in a configuration of 1900
      monomers there are, on average, only three voids large enough to incorporate a
      spherical particle as large as a monomer, indicating that the density of the
      large vacancies in the system is considerably, i.e., by a few orders of magnitude
      lower than in molecular liquids corresponding to roughly the same reduced
      densities.

PMID- 15260798
TI  - Oppositely charged colloidal binary mixtures: a colloidal analog of the
      restricted primitive model.
AB  - The equilibrium phase diagram of a colloidal system composed of 1:1 mixture of
      positive and negative particles with equal charge is studied by means of Monte
      Carlo simulations. The system is the colloidal analog of the restricted primitive
      model (RPM) for ionic fluids. A liquid-gas transition is found in the low
      temperature-low-density region, similar to the liquid-gas transition in the RPM.
      The fluid-crystal transition is also studied, and the liquid phase is shown to be
      stable in a narrow range of temperatures. In the liquid, the pair distribution
      function shows alternating layers of particles with opposite sign of charge
      surrounding every particle. In the vapor phase, clusters of particles are
      observed, again in agreement with the RPM. However, a decreasing distribution of
      clusters is obtained, instead of the discrimination between charged and neutral
      clusters found in the RPM.

PMID- 15260799
TI  - Biomolecular free energy profiles by a shooting/umbrella sampling protocol,
      "BOLAS".
AB  - We develop an efficient technique for computing free energies corresponding to
      conformational transitions in complex systems by combining a Monte Carlo ensemble
      of trajectories generated by the shooting algorithm with umbrella sampling.
      Motivated by the transition path sampling method, our scheme "BOLAS" (named after
      a cowboy's lasso) preserves microscopic reversibility and leads to the correct
      equilibrium distribution. This makes possible computation of free energy profiles
      along complex reaction coordinates for biomolecular systems with a lower
      systematic error compared to traditional, force-biased umbrella sampling
      protocols. We demonstrate the validity of BOLAS for a bistable potential, and
      illustrate the method's scope with an application to the sugar repuckering
      transition in a solvated deoxyadenosine molecule.

PMID- 15260800
TI  - Optically nonlinear energy transfer in light-harvesting dendrimers.
AB  - Dendrimeric polymers are the subject of intense research activity geared towards
      their implementation in nanodevice applications such as energy harvesting
      systems, organic light-emitting diodes, photosensitizers, low-threshold lasers,
      and quantum logic elements, etc. A recent development in this area has been the
      construction of dendrimers specifically designed to exhibit novel forms of
      optical nonlinearity, exploiting the unique properties of these materials at high
      levels of photon flux. Starting from a thorough treatment of the underlying
      theory based on the principles of molecular quantum electrodynamics, it is
      possible to identify and characterize several optically nonlinear mechanisms for
      directed energy transfer and energy pooling in multichromophore dendrimers. Such
      mechanisms fall into two classes: first, those where two-photon absorption by
      individual donors is followed by transfer of the net energy to an acceptor;
      second, those where the excitation of two electronically distinct but neighboring
      donor groups is followed by a collective migration of their energy to a suitable
      acceptor. Each transfer process is subject to minor dissipative losses. In this
      paper we describe in detail the balance of factors and the constraints that
      determines the favored mechanism, which include the excitation statistics,
      structure of the energy levels, laser coherence factors, chromophore selection
      rules and architecture, possibilities for the formation of delocalized excitons,
      spectral overlap, and the overall distribution of donors and acceptors.
      Furthermore, it transpires that quantum interference between different mechanisms
      can play an important role. Thus, as the relative importance of each mechanism
      determines the relevant nanophotonic characteristics, the results reported here
      afford the means for optimizing highly efficient light-harvesting dendrimer
      devices.

PMID- 15260802
TI  - Effects of pH on Helicobacter pylori binding to human gastric mucins:
      identification of binding to non-MUC5AC mucins.
AB  - Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer.
      The microbe is found in the gastric mucus layer where a pH gradient ranging from
      acidic in the lumen to neutral at the cell surface is maintained. The aim of the
      present study was to investigate the effects of pH on H. pylori binding to
      gastric mucins from healthy individuals. At pH 3, all strains bound to the most
      charged MUC5AC glycoform and to a putative mucin of higher charge and larger size
      than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast,
      at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC
      and to smaller mucin-like molecules, including MUC1. H. pylori binding to the
      latter component(s) seems to occur via the H-type-1 structure. All strains bound
      to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains
      at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound
      strains occurred both at neutral and acidic pH. The binding properties at acidic
      pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH
      occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on
      the glycoprotein. Our work shows that microbe binding to membrane-bound mucins
      must be considered in H. pylori colonization, and the potential of these
      glycoproteins to participate in signalling events implies that microbe binding to
      such structures may initiate signal transduction over the epithelial layer.
      Competition between microbe binding to membrane-bound and secreted mucins is
      therefore an important aspect of host-microbe interaction.

PMID- 15260801
TI  - Dual sensitivity of sarcoplasmic/endoplasmic Ca2+-ATPase to cytosolic and
      endoplasmic reticulum Ca2+ as a mechanism of modulating cytosolic Ca2+
      oscillations.
AB  - The effects of ER (endoplasmic reticulum) Ca2+ on cytosolic Ca2+ oscillations in
      pancreatic acinar cells were investigated using mathematical models of the Ca2+
      oscillations. We first examined the mathematical model of SERCA
      (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) to reproduce the highly co
      operative inhibitory effect of Ca2+ in the ER lumen on ER Ca2+ uptake in the
      acinar cells. The model predicts that luminal Ca2+ would most probably inhibit
      the conversion of the conformation state with luminal Ca2+-binding sites (E2)
      into the conformation state with cytoplasmic Ca2+-binding sites (E1). The SERCA
      model derived from this prediction showed dose-response relationships to
      cytosolic and luminal Ca2+ concentrations that were consistent with the
      experimental data from the acinar cells. According to a mathematical model of
      cytosolic Ca2+ oscillations based on the modified SERCA model, a small decrease
      in the concentration of endoplasmic reticulum Ca2+ (approx. 20% of the total) was
      sufficient to abolish the oscillations. When a single type of IP3R (IP3 receptor)
      was included in the model, store depletion decreased the spike frequency.
      However, the frequency became less sensitive to store depletion when we added
      another type of IP3R with higher sensitivity to the concentration of free Ca2+ in
      the cytosol. Bifurcation analysis of the mathematical model showed that the loss
      of Ca2+ from the ER lumen decreased the sensitivity of cytosolic Ca2+
      oscillations to IP3 [Ins(1,4,5)P3]. The addition of a high-affinity IP3R did not
      alter this property, but significantly decreased the sensitivity of the spike
      frequency to IP3. Our mathematical model demonstrates how luminal Ca2+, through
      its effect on Ca2+ uptake, can control cytosolic Ca2+ oscillations.

PMID- 15260803
TI  - Why is open-access publishing the answer?

PMID- 15260804
TI  - Electroporation enhances transfection efficiency in murine cutaneous wounds.
AB  - Transfection of wounds with DNA-encoding growth factors has the potential to
      improve healing, but current means of nonviral gene delivery are inefficient.
      Repeated high doses of DNA, necessary to achieve reliable gene expression, are
      detrimental to healing. We assessed the ability of in vivo electroporation to
      enhance gene expression. Full-thickness cutaneous excisional wounds were created
      on the dorsum of female mice. A luciferase- encoding plasmid driven by a CMV
      promoter was injected at the wound border. Following plasmid administration,
      electroporative pulses were applied to injection sites. Pulse parameters were
      varied over a range of voltage, duration, and number. Animals were euthanized at
      intervals after transfection and the luciferase activity measured. Application of
      electric pulses consistently increased luciferase expression. The electroporative
      effect was most marked at a plasmid dose of 50 micro g, where an approximate
      tenfold increase was seen. Six 100- micro s-duration pulses of 1750 V/cm were
      found to be the most effective in increasing luciferase activity. High numbers of
      pulses tended to be less effective than smaller numbers. This optimal
      electroporation regimen had no detrimental effect on wound healing. We conclude
      that electroporation increases the efficiency of transgene expression and may
      have a role in gene therapy to enhance wound healing.

PMID- 15260805
TI  - Growth hormone effects on hypertrophic scar formation: a randomized controlled
      trial of 62 burned children.
AB  - The hypercatabolism after massive pediatric burns has been effectively treated
      with recombinant human growth hormone, an anabolic agent that stimulates protein
      synthesis and abrogates growth arrest. While experimental studies have shown
      increased potential for fibrosis induced by growth hormone therapy, adverse
      effects on human scars have not been investigated. Our aim was to evaluate
      hypertrophic scar formation in 62 patients randomized to receive injections of
      0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge
      until 1 year after burn. Scar scales were used to evaluate scar-severity at
      discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to
      treatment. Computer-assisted planimetry allowed quantification of percentage of
      hypertrophic scar formation. Types I and III collagens were localized and
      quantified in scars and normal skin of patients from both groups, using
      immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth
      factor-1 blood levels helped assess compliance. Statistical analysis showed that
      scar hypertrophy significantly increased from 6 to 12 months after injury in both
      groups, while decreasing at 18-24 months postburn. Types I and III collagens were
      statistically increased in the reticular layer of scars from both groups when
      compared to paired normal skin. Insulin-like growth factor-1 was significantly
      increased in the recombinant human growth factor-treated group. No differences
      were seen when recombinant human growth factor and control groups were compared
      using the scar scales, planimetry, or immunohistochemistry. We concluded that
      recombinant human growth hormone therapy did not adversely affect scar formation
      and should not contraindicate the administration of recombinant human growth
      hormone as a therapeutic approach to severely burned children.

PMID- 15260806
TI  - Predictive and monitoring value of matrix metalloproteinase-9 for healing quality
      after sinus surgery.
AB  - Functional endoscopic sinus surgery is considered the standard therapeutic
      procedure for chronic rhinosinusitis and nasal polyposis after failure of medical
      treatment. We tested the hypothesis that the healing outcome after surgery was
      correlated to the secretion profile of gelatinase-B (matrix metalloproteinase-9
      [MMP-9]) and transforming growth factor-beta1 (TGF-beta1) in nasal fluid. We
      performed a prospective study in 36 patients bilaterally operated for chronic
      rhinosinusitits or nasal polyposis and the healing quality was evaluated until 6
      months after surgery by standardized nasal endoscopy, using a visual analog
      scale. Before functional endoscopic sinus surgery and during the postoperative
      period, TGF-beta1 and MMP-9 in nasal secretions were measured by enzyme-linked
      immunosorbent assay. Both MMP-9 and TGF-beta1 showed a significant increase
      initially after surgery. The healing quality after 6 months was significantly and
      independently correlated to preoperative MMP-9 concentrations in nasal secretions
      (p = 0.03), initial disease (p = 0.03), and previous sinus surgery (p = 0.004).
      Furthermore, concentrations of MMP-9 were significantly lower in patients with
      good healing (visual analog scale < 3) from week 3 to month 6 compared to
      patients with poor healing. MMP-9 is the first objective factor suitable to
      predict and monitor the healing quality after sinus surgery, indicating MMP-9 as
      a possible therapeutic target.

PMID- 15260807
TI  - Comparison of oxidative stress biomarker profiles between acute and chronic wound
      environments.
AB  - Increasing evidence implicates excessive reactive oxygen species (ROS) generation
      and ROS-derived degradation products in the pathogenesis of many skin diseases.
      While numerous attempts have been made to identify prognostic biomarkers of wound
      healing in skin, these have met with limited success. This study examined the
      profiles of various oxidative stress biomarkers, namely total protein carbonyl
      content (from protein oxidation), malondialdehyde content (from lipid
      peroxidation), and the total antioxidant capacities, in acute wound fluid (n= 10)
      and chronic wound fluid (n= 12), using a rapid, noninvasive collection technique.
      Protein carbonyl content was quantified spectrophotometrically and by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis/Western blotting, following
      2,4-dinitrophenylhydrazine derivitization. Malondialdehyde levels were similarly
      quantified, following N-methyl-2-phenylindole derivitization. Total antioxidant
      capacity was determined via wound fluid inhibition of cytochrome C reduction by a
      superoxide radical flux. Acute wound fluid contained higher protein carbonyl
      content than chronic wound fluid, particularly evident following sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis/Western blot analysis under
      nonreducing and reducing conditions (p < 0.001 and p < 0.02, respectively),
      related to significantly higher protein levels (p = 0.0005) in acute wound fluid.
      Human serum albumin ( approximately 66 kDa) was identified as the most prominent
      protein oxidized in both acute and chronic wound fluid, which may contribute to
      the reduced albumin and total protein levels in chronic wound fluid. No
      significant difference (p > 0.1) in malondialdehyde levels or total antioxidant
      capacities were determined between acute and chronic wound fluids, although
      chronic wound fluid exhibited significantly higher total antioxidant capacities
      (p < 0.005), accounting for variations in wound fluid protein content. These
      findings suggest an adaptation in the antioxidant profiles of chronic wound fluid
      to counteract the loss of consumed antioxidants in the chronic wound environment.
      This study highlights the roles of ROS/antioxidants in skin wound healing, their
      possible involvement in chronic wounds and the potential value of ROS-induced
      biomarkers in wound healing prognosis.

PMID- 15260808
TI  - Alpha-smooth muscle actin in pathological human disc nucleus pulposus cells in
      vivo and in vitro.
AB  - That a contractile actin isoform has been found in cells of other cartilage
      tissues in healing and disease states prompted this investigation of the presence
      of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral
      disc tissue. The presence of this isoform has been reported in human
      intervertebral disc specimens obtained at autopsy from subjects for whom there
      were no reported symptoms. An objective of this study was to evaluate the cell
      density and percentage of alpha-SMA-containing cells in pathological nucleus
      pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally,
      explants of nucleus pulposus material were cultured to determine how alpha-SMA
      expression changed with time in vitro. Seventy-six 5-mm diameter explants
      (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1,
      2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained
      with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically,
      cells were categorized as to alpha-SMA phenotype (positive or negative), and the
      areal cell density was determined. The evaluation of the cultured nucleus
      pulposus explants also included documentation of the percentage of cells that
      were round or elongated and the percentage of the cells that were part of a group
      (group: >/= 2 cells). Every nucleus pulposus section exhibited the presence of
      alpha-SMA-containing cells, which accounted for approximately 24 percent of the
      cells in vivo. In vivo, the cell density was significantly higher in older
      individuals (p = 0.02). The average time for cell outgrowth from the explants was
      8.6 days. Approximately 10-15 percent of the cells in the explants stained
      positive for alpha-SMA. The time in culture had no significant effect on any of
      the outcome measures except the percentage of alpha-SMA-containing cells that
      were round (p = 0.008), with values decreasing through 4 weeks and then slightly
      rising at 6 weeks. The role of alpha-SMA in intervertebral disc pathology
      warrants further investigation.

PMID- 15260809
TI  - Human beta-defensin-2 expression is increased in chronic wounds.
AB  - First identified in psoriatic epidermis and subsequently in other inflammatory
      cutaneous lesions, human beta-defensin-2 (hbetaD-2) is one of two endogenous
      antimicrobial peptides related to defensins in plants and animals. Our objective
      was to determine the expression of hbetaD-2 after injury and in chronic wounds.
      Biopsies of normal ipsilateral thigh skin and wound edges were taken from nine
      consecutive patients with venous leg ulcers (day 1) and from the same biopsy
      sites 2 days later (day 3). Sequential samples were also obtained from intact or
      meshed bilayered bioengineered skin consisting of neonatal human keratinocytes
      and dermal fibroblasts in a collagen matrix. Specimens were processed and
      immunostained for hbetaD-2 using a polyclonal rabbit antibody. In both human
      tissues and bioengineered skin, staining for hbetaD-2 was confined to the upper
      epidermal layers, sparing the basal cells. Analysis of 26 tissue samples from
      patients showed that normal skin had no hbetaD-2 expression but that marked up
      regulation occurred after wounding by day 3. Conversely, chronic ulcers showed
      moderate-to-strong immunostaining for hbetaD-2 at baseline on day 1, with little
      or no change in intensity after wounding by day 3. In vitro, bioengineered skin
      showed increased distribution of cytoplasmic hbetaD-2 immunostaining after
      meshing. We conclude that the expression of hbetaD-2 is up-regulated after
      injury. Chronic wounds uniformly show a constitutively high baseline expression
      of hbetaD-2, possibly due to ongoing tissue injury and bacterial colonization.

PMID- 15260810
TI  - Pig chondrocyte xenoimplants for human chondral defect repair: an in vitro model.
AB  - The objective of this study was to evaluate the use of cultured porcine
      chondrocyte xenotransplantation for the repair of human chondral defects. Two
      millimeter-diameter defects were drilled into explants of femoral cartilage from
      healthy adult donors. No cells were implanted in the chondral defects of the
      control group, while pig chondrocytes from normal femoral cartilage were
      deposited into the treated chondral defects. Cartilage explants were cultured for
      4, 8, and 12 weeks. Tissue sections were processed for standard histologic
      staining and immunostaining with monoclonal antibodies against types I and II
      collagen, chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and
      integrin subunit beta1. The porcine origin of chondrocytes was confirmed using a
      specific pig monoclonal anti-CD46. Repair was only observed in the cell-treated
      defects. Mono- or bilayers of cells were detected after 4 culture weeks on the
      bottom of the defects, while after 8-12 weeks a repair tissue filled near 30-40
      percent of the defect. At 8 weeks, the newly synthesized tissue was composed of a
      fibrous mesh including some cells. However, at 12 weeks it showed a hypercellular
      hyaline-like region. This hypercellular region showed excellent bonding with the
      native cartilage, cells were located in numerous lacunae, and a high content of
      proteoglycans as indicated by an intense toluidine blue stain was observed. The
      repaired tissue showed positive immunostaining for both type I and II collagen,
      as well as chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and
      integrin subunit beta1. Positive staining for porcine anti-CD46 was localized
      exclusively in the neo-synthesized tissue. We conclude that xenotransplantation
      of pig chondrocytes can repair, in an in vitro model, defects in human articular
      cartilage.

PMID- 15260811
TI  - Bioelastic membranes for topical application of a thromboxane synthetase
      inhibitor for protection of skin from pressure injury: a preliminary study.
AB  - A previous study showed that topical exposure to bioelastic-thromboxane
      synthetase inhibitor-matrix resulted in local tissue concentrations of
      thromboxane synthetase inhibitor sufficient for thromboxane synthetase
      inhibition. The objective of this research was to use an animal model to
      determine if a dressing having controlled release of thromboxane synthetase
      inhibitor (dazmegrel) could be used to prevent tissue breakdown over pressure
      points, i.e., lesion at the assistive device-skin interface. The animal model
      studies utilized the greyhound, a dog that has thin skin, angular conformation,
      limited body fat and is predisposed to pressure ulcers similar to those occurring
      in humans. The model uses a short-limb walking cast on one pelvic limb with the
      severity of the dermal pressure lesions induced over the medial malleolus
      controlled by the amount of padding in the cast and length of time the cast is in
      place. The bioelastic matrix loaded with dazmegrel provided protection from
      shearing and pressure skin injury over the medial malleolus, as evidenced by a
      decrease in epidermal abrasion/ulceration as measured with planimetry.
      Histopathologic evaluation of the skin over the medial malleolus indicated a
      protective function of the bioelastic matrix as measured as lower numbers of
      neutrophils, lymphocytes, and decreased collagen density compared to such numbers
      when no bioelastic matrix was present. These studies provided evidence that
      bioelastic-thromboxane sythetase inhibitor- matrix helps in preventing or
      reducing the severity of pressure lesions, e.g., assistive device-skin interface
      wounds.

PMID- 15260812
TI  - AlphaV integrins play an important role in myofibroblast differentiation.
AB  - Transforming growth factor-beta1 is a potent mediator of the differentiation of
      fibroblasts into myofibroblasts, which is characterized by the appearance of the
      cytoskeletal protein alpha-smooth muscle actin. The aim of this study was to
      investigate the role of integrin extracellular matrix receptors in transforming
      growth factor-beta1-induced myofibroblast differentiation. We show that blockade
      of the alphav and/or beta1 integrins prevents the transforming growth factor
      beta1-induced myofibroblast differentiation, seen by the increased expression of
      alpha-smooth muscle actin and enhanced collagen gel contraction in three human
      fibroblast cell lines (from the mouth, skin, and kidney). Further, blockade of
      alphav specific integrins alphavbeta5 and alphavbeta3 suppressed myofibroblast
      differentiation in fibroblasts from the mouth and skin; however, in the kidney
      cells, the prevention of differentiation was seen only with blockade of
      alphavbeta5 integrin but not alphavbeta3. A possible reason for this result may
      be different degrees of responsiveness to transforming growth factor-beta1
      treatment seen from different anatomical origins of the cell lines. These data
      indicate a novel role for alphav integrins in the differentiation of human
      fibroblasts from the mouth, skin, and kidney into myofibroblasts and suggest that
      there is a common differentiation pathway.

PMID- 15260814
TI  - Quantitative and reproducible murine model of excisional wound healing.
AB  - The goal of animal wound healing models is to replicate human physiology and
      predict therapeutic outcomes. There is currently no model of wound healing in
      rodents that closely parallels human wound healing. Rodents are attractive
      candidates for wound healing studies because of their availability, low cost, and
      ease of handling. However, rodent models have been criticized because the major
      mechanism of wound closure is contraction, whereas in humans reepithelialization
      and granulation tissue formation are the major mechanisms involved. This article
      describes a novel model of wound healing in mice utilizing wound splinting that
      is accurate, reproducible, minimizes wound contraction, and allows wound healing
      to occur through the processes of granulation and reepithelialization. Our
      results show that splinted wounds have an increased amount of granulation tissue
      deposition as compared to controls, but the rate of reepithelialization is not
      affected. Thus, this model eliminates wound contraction and allows rodents'
      wounds to heal by epithelialization and granulation tissue formation. Given these
      analogies to human wound healing, we believe that this technique is a useful
      model for the study of wound healing mechanisms and for the evaluation of new
      therapeutic modalities.

PMID- 15260813
TI  - Firsthand cigarette smoke alters fibroblast migration and survival: implications
      for impaired healing.
AB  - Although it is known that high levels of cigarette smoke lead to cell death,
      little is known about the effects of low-to-moderate levels of smoke components
      that are found in vivo, such as those experienced by cells in tissues. Clinical
      studies and experimental data show that smokers heal poorly and are more prone to
      develop fibrotic diseases. Here we show the effects of first-hand cigarette smoke
      on fibroblasts, cells that are critically involved in these processes. Using
      doses of smoke found in the tissues of smokers and a variety of cell and
      molecular approaches, we show that these doses of cigarette smoke do not cause
      cell death but rather stimulate fibroblasts to produce stress response and
      survival proteins such as interleukin-8, PKB/Akt, p53, and p21 that in turn
      contribute to an increase in cell survival. In addition, smoke-treated cells show
      a decrease in cell migration, which can be explained by the increased cell
      adhesion and alterations in cytoskeletal elements. We also show that these levels
      of smoke cause changes in mitochondrial morphology with a minimum loss of
      function and these changes are the result of exposure to reactive oxygen species.
      We conclude that the increase in cell survival may lead to a build-up of
      connective tissue in the area of a wound, potentially leading to delayed healing
      and/or fibrosis and that the alterations in the cytoskeleton and in cell adhesion
      result in inhibition of cell migration, a process that could lead to nonclosure
      of the wound for lack of proper fibroblast migration to form the healing tissue.

PMID- 15260816
TI  - Induction of latent human cytomegalovirus by conventional gamma irradiation and
      prevention by treatment with INACTINE PEN110.
AB  - BACKGROUND AND OBJECTIVES: Two different leucocyte-inactivation technologies-
      gamma irradiation and INACTINE PEN110--were evaluated for their effects on cell
      associated human cytomegalovirus (CMV). MATERIALS AND METHODS: In vitro CMV
      infected cells were spiked into leucoreduced red blood cell concentrates (RCC) or
      medium at a final concentration of 0.5 - 1 x 10(7) cells/ml to mimic non
      leucoreduced levels of leucocytes. The spiked RCC/medium was divided into three
      equal units and treated with gamma irradiation at the US Food and Drug
      Administration (FDA)-approved dose of 25 Gy, with 0.1% v/v PEN110 at 22 degrees C
      for 24 h, or stored at 4 degrees C as a control. The treated and control cells
      were recovered and tested using infectivity, viability and polymerase chain
      reaction (PCR) assays. RESULTS: Gamma-irradiated CMV-infected cells produced
      active virus, as shown by both infectivity assays and PCR quantification of viral
      DNA. PCR analysis demonstrated higher CMV DNA levels in gamma-irradiated,
      latently infected monocytic THP-1 cells than untreated control cells. The
      increased virus production in gamma-irradiated cells was paralleled by an
      increased metabolic rate and the development of enlarged multinuclear cells. In
      contrast, PEN110 treatment terminated virus replication and completely
      inactivated the infected cell. CONCLUSIONS: These results demonstrate that gamma
      irradiation, at levels currently used to treat RCC, has the capacity to induce
      expression of CMV, whereas PEN110 inhibits CMV replication and efficiently
      inactivates the infected cells.

PMID- 15260817
TI  - Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant
      and emergent viral pathogens in plasma-derived products.
AB  - BACKGROUND AND OBJECTIVES: Human plasma is the source of a wide variety of
      therapeutic proteins, yet it is also a potential source of viral contamination.
      Recent outbreaks of emergent viral pathogens, such as West Nile virus, and the
      use of live vaccinia virus as a vaccine have prompted a reassessment of the viral
      safety of plasma-derived products. The purpose of this study was to evaluate the
      efficacy of current viral inactivation methods for West Nile and vaccinia viruses
      and to reassess the use of model viruses to predict inactivation of similar viral
      pathogens. MATERIALS AND METHODS: Virus-spiked product intermediates were
      processed using a downscaled representation of various manufacturing procedures.
      Virus infectivity was measured before and after processing to determine virus
      inactivation. RESULTS: The results demonstrated effective inactivation of West
      Nile virus, vaccinia virus and a model virus, bovine viral diarrhoea virus,
      during pasteurization, solvent/detergent treatment and caprylate treatment.
      Caprylate provided rapid and effective inactivation of West Nile virus, vaccinia
      virus, duck hepatitis B virus and Sindbis virus. Inactivation of West Nile virus
      was similar to that of bovine viral diarrhoea virus. CONCLUSIONS: This study
      demonstrates that procedures used to inactivate enveloped viruses in
      manufacturing processes can achieve inactivation of West Nile virus and vaccinia
      virus. In addition, the data support the use of model viruses to predict the
      inactivation of similar emergent viral pathogens.

PMID- 15260818
TI  - The in vitro quality of washed, prestorage leucocyte-depleted red blood cell
      concentrates.
AB  - BACKGROUND AND OBJECTIVES: No data are currently available on the quality of
      washed prestorage leucocyte-depleted red blood cell concentrates (RCCs).
      MATERIALS AND METHODS: Five groups of RCCs stored in additive solution (SAG-M)
      were washed. The groups differed in the age of RCCs (2-5 days or 11-15 days), the
      temperature during the washing procedure and a 6-h storage period (4 degrees C or
      room temperature) and the washing solution (saline, SAG-M or 5% albumin). We
      measured ATP, 2,3-diphosphoglycerate (2,3-DPG), haemolysis, blood cell count,
      Na(+), K(+), pH, pO(2), pCO(2) and lactate, before and after the washing
      procedure and hourly during the 6-h postwash storage period. RESULTS: The
      erythrocyte ATP content increased by 2-13%, relative to the baseline value,
      during the washing procedure. The 2,3-DPG level decreased by 15-35% in 2-6-day
      old RCCs and by 30-40% in 11-15-day-old RCCs (relative to baseline values) during
      the washing procedure. In RCCs that were washed and stored at room temperature,
      and in 2-week-old RCCs, a further decrease in 2,3-DPG of up to 40%, relative to
      the baseline value, was observed during the 6-h postwash time-period.
      CONCLUSIONS: Washing of RCCs stored in SAG-M results in a considerable,
      significant loss of erythrocyte 2,3-DPG, especially in older RCCs. This loss
      increases in during a 6-h storage period postwash, even at 4 degrees C. This loss
      of erythrocyte quality might well outweigh the benefits of washed SAG-M RCCs
      during massive transfusion in neonates.

PMID- 15260819
TI  - Content and functional activity of von Willebrand factor in apheresis plasma.
AB  - BACKGROUND AND OBJECTIVES: Von Willebrand Factor (VWF) is a complex high
      molecular-weight (HMW) plasma glycoprotein playing a critical role in primary and
      secondary haemostasis. Owing to its multimeric structure and sensitivity to
      proteolysis, VWF can be used as a marker of the impact of collection procedures
      on the characteristics of plasma for transfusion and for fractionation. We
      studied VWF content, functional activity and HMW multimers in plasmas collected
      by five different automated apheresis collection procedures. MATERIALS AND
      METHODS: Five series of 30 plasma units were obtained from volunteer donors at
      two collection sites using Haemonetics PCS2 machines with Revision (Rev) F, Rev
      G, high-separation core (HSC), or filter core (FC) procedures, or Baxter-Fenwall
      Autopheresis-C (Auto-C). VWF antigen (VWF:Ag), ristocetin cofactor (VWF:RCo)
      activity and HMW multimers were first determined in 10 randomly selected plasma
      donations collected with Rev G, HSC, FC and Auto-C procedures. Then, the same
      analyses and the collagen binding (VWF:CB) activity were determined in the pools
      of 30 donations from each of the five procedures and compared with two normal
      plasma pools (NPP1 and NPP2). A reference plasma (RP) was used to calibrate each
      assay. RESULTS: There were a greater number of group O individuals in the Rev F,
      Rev G and FC donors than in the HSC and Auto-C donors. The mean VWF:Ag level was
      > 100 IU/dl, VWF:RCo activity was > 90 U/dl, the VWF:RCo/Ag ratio was close to 1,
      and the percentage of 11-15 mers was above 100% of RP in the 10 individual plasma
      units from Rev G, HSC, FC, and Auto-C and in their respective pools. The mean
      percentage of multimers > 15 mers, relative to RP, was significantly less in Rev
      G plasmas (48 +/- 17%; range 32-91%), compared with Auto-C, HSC and FC plasmas (P
      = 0.0211; 0.0257; and 0.0376, respectively). The VWF:CB activity of the 30
      donation pools was 61 and 60 U/dl in Auto C and HSC, 50 U/dl in Rev F and FC, and
      43 U/dl in the Rev G pool. The VWF:CB/Ag ratio was 0.54 (Auto-C), 0.49 (HSC),
      0.46 (Rev F), 0.45 (FC) and 0.37 (Rev G), compared with 0.81and 0.92 in NPPs. The
      percentage of VWF multimers of 11-15 mers in apheresis plasma and NPP was normal.
      VWF multimers > 15 mers ranged from 38 to 64% of that of RP plasma, and was 111
      and 112% in NPPs. CONCLUSIONS: The VWF:Ag, VWF:RCo activity and 11-15 mer VWF
      multimers were well preserved in all plasma units from each of the five apheresis
      procedures. The VWF:CB activity and the percentage of multimers > 15 mers in
      apheresis plasma was less than in normal plasma pools and differed slightly among
      procedures.

PMID- 15260820
TI  - Recombinant activated factor VII (NovoSeven): addition to replacement therapy in
      acute, uncontrolled and life-threatening bleeding.
AB  - BACKGROUND AND OBJECTIVES: Recombinant activated factor VII (rFVIIa, NovoSeven)
      has been used off-label for various conditions. A protocol for its use in acute,
      uncontrolled life-threatening bleeding, was devised and employed. A
      haematologist/transfusion specialist was assigned as a member of the team.
      MATERIALS AND METHODS: The clinical data were reviewed and summarized. A scoring
      system for the assessment and monitoring of coagulopathy was employed. Each
      parameter of prothrombin time (PT), activated partial thromboplastin time (aPTT),
      platelet number and fibrinogen level was allocated points according to the degree
      of abnormality. Three scoring levels emerged. RESULTS: Between April 2001 and
      April 2003, 13 patients received rFVIIa for acute, uncontrolled life-threatening
      bleeding. Nine of 13 patients remained alive for 15 days or longer after rFVIIa
      infusion. All patients who experienced a reduction or cessation of bleeding after
      rFVIIa infusion, also had a lower coagulopathy score after replacement therapy,
      prior to rFVIIa infusion, compared with their score at rFVIIa request. There was
      a reduction in the average use of blood products after rFVIIa infusion. The
      coagulopathy score was statistically predictive of response to rFVIIa and
      survival. CONCLUSIONS: In an area where very little data exists, we report the
      usefulness of rFVIIa. We propose that transfusion replacement should aim to
      correct coagulopathy before infusion of rFVIIa and that a
      haematologist/transfusion specialist should be involved in the management of
      these patients. A prognostically significant coagulopathy scoring system is
      offered.

PMID- 15260821
TI  - The serological and genetic basis of the cis-AB blood group in Korea.
AB  - BACKGROUND AND OBJECTIVES: The cis-AB blood group is rare, although relatively
      common amongst Koreans. The serological characteristics and genetic basis of
      Korean cis-AB blood donors were investigated. MATERIALS AND METHODS: Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP), designed to
      detect the cis-AB01 allele, was performed on 194 AB samples which demonstrated
      weak or unusual expression of either or both of the A or B antigens. RESULTS AND
      CONCLUSIONS: Sixty cis-AB01 donors were identified. cis-AB01/O01 or O02 were the
      most common genotypes (36/60) detected only in A(2)B(3) donors, and cis-AB01/B101
      (nine of 60) was the least common genotype identified only in A(2)B donors.
      Surprisingly cis-AB01/A102 (15/60) was identified in a variety of phenotypes
      (A(1)B(3), A(1)B(x) or el, A(int)B(3)).

PMID- 15260822
TI  - First human immunodeficiency virus-1 group O infection in a European blood donor.

PMID- 15260823
TI  - Apoptosis of T and B lymphocytes, natural killer cells and monocytes contained in
      packed red blood cells.

PMID- 15260824
TI  - Transfusion safety in the hospital.

PMID- 15260826
TI  - Chlamydia--host cell interactions: recent advances on bacterial entry and
      intracellular development.
AB  - Bacteria of the Chlamydiales order are very successful intracellular organisms
      that grow in human and animal cells, and even in amoebae. They fulfill several
      essential functions to enter their host cells, establish an intracellular
      environment favorable for their multiplication and exit the host cell. They
      multiply in a unique organelle called the inclusion, which is isolated from the
      endocytic but not the exocytic pathway. A combination of host cell factors and of
      proteins secreted by the bacteria, from within the inclusion, contribute to the
      establishment and development of this inclusion. Here we review recent data on
      the entry mechanisms and maturation of the inclusion.

PMID- 15260827
TI  - Annexin-actin interactions.
AB  - The actin cytoskeleton is a malleable framework of polymerised actin monomers
      that may be rapidly restructured to enable diverse cellular activities such as
      motility, endocytosis and cytokinesis. The regulation of actin dynamics involves
      the coordinated activity of numerous proteins, among which members of the annexin
      family of Ca2+- and phospholipid-binding proteins play an important role.
      Although the roles of annexins in actin dynamics are not understood at a
      mechanistic level, annexins have the requisite properties to integrate Ca2+
      signaling with actin dynamics at membrane contact sites. In this review we
      discuss the current state of knowledge on this topic, and consider how and where
      annexins may fit into the complex molecular machinery that regulates the actin
      cytoskeleton.

PMID- 15260828
TI  - Protein kinase C-alpha and -delta are required for FcalphaR (CD89) trafficking to
      MHC class II compartments and FcalphaR-mediated antigen presentation.
AB  - Studies have demonstrated that receptor-mediated signaling, receptor/antigen
      complex trafficking, and major histocompatibility complex class II compartments
      (MIIC) are critically related to antigen presentation to CD4+ T cells. In this
      study, we investigated the role of protein kinase C (PKC) in FcalphaR/gammagamma
      (CD89, human IgA receptor)-mediated internalization of immune complexes and
      subsequent antigen presentation. The classical and novel PKC inhibitor,
      Calphostin C, inhibits FcalphaR-mediated antigen presentation and interaction of
      MIIC and cargo vesicle (receptor and antigen). PKC-alpha, PKC-delta, and PKC
      epsilon were recruited to lipid rafts following FcalphaR crosslinking, the extent
      of which was determined by the phenotype of the gamma chain. Mutant gamma chain
      with an FcgammaRIIA ITAM (immunoreceptor tyrosine-based activation motif) insert
      was less able to recruit PKC and trigger antigen presentation. Both PKC isoform
      specific peptide inhibitors and short interfering RNA (siRNA) showed that PKC
      alpha and PKC-delta, but not PKC-epsilon, were required for association of cargo
      vesicle and MIIC and for FcalphaR-mediated and soluble antigen presentation.
      Inhibition of PKC (classical and novel) did not alter major histocompatibility
      class II biosynthesis, assembly, transport, or plasma membrane stability. PKC's
      role in facilitating interaction of cargo vesicle and MIIC is likely due to
      regulation of vesicle biology required for fusion of cargo vesicles to MIIC.

PMID- 15260829
TI  - Dynamic nucleation of Golgi apparatus assembly from the endoplasmic reticulum in
      interphase hela cells.
AB  - Models of Golgi apparatus biogenesis and maintenance are focused on two
      possibilities: one is self-assembly from the endoplasmic reticulum, and the other
      is nucleation by a stable template. Here, we asked in three different
      experimental situations whether assembly of the Golgi apparatus might be
      dynamically nucleated. During microtubule depolymerization, the integral membrane
      protein p27 and the peripheral Golgi protein GM130, appeared in newly formed,
      scattered Golgi elements before three different Golgi apparatus cisternal
      enzymes, whereas GRASP55, a medial peripheral Golgi protein, showed, if anything,
      a tendency to accumulate in scattered Golgi elements later than a cisternal
      enzyme. During Golgi formation after brefeldin A washout, endoplasmic reticulum
      exit of Golgi resident enzymes could be completely separated from that of p27 and
      GM130. p27 and GM130 accumulation was onto newly organized perinuclear
      structures, not brefeldin A remnants, and preceded that of a cisternal enzyme.
      Reassembly was completely sensitive to guanosine 5'-diphosphate-restricted Sar1p.
      When cells were microinjected with Sar1pWT DNA to reverse a guanosine 5'
      diphosphate-restricted Sar1p endoplasmic reticulum-exit block phenotype, GM130
      and p27 collected perinuclearly with little to no exit of a cisternal enzyme from
      the endoplasmic reticulum. The overall data strongly indicate that the assembly
      of the Golgi apparatus can be nucleated dynamically by GM130/p27 associated
      structures. We define dynamic nucleation as the first step in a staged organelle
      assembly process in which new component association forms a microscopically
      visible structure onto which other components add later, e.g. Golgi cisternae.

PMID- 15260830
TI  - Continual expression of Rab5(Q79L) causes a ligand-independent EGFR
      internalization and diminishes EGFR activity.
AB  - The amount of cell-surface Epidermal Growth Factor Receptor (EGFR) available to
      secreted ligand (EGF) dictates a cell's ability to mediate cell proliferation,
      differentiation or migration. Multiple factors regulate EGFR cell-surface
      expression including the rates of protein synthesis and protein degradation, and
      the endocytic trafficking of both stimulated and unstimulated EGFR. Rab5 is a 25
      kDa protein that is localized to the plasma membrane and the early endosome. Its
      exact molecular function, however, remains controversial. We have used stable and
      transient expression systems in HeLa cells to examine the consequence of
      continual, overexpression of wild-type and activated mutants of rab5 on EGFR
      localization and signaling. Continual expression of constitutively activated
      mutants of rab5 causes a ligand-independent redistribution of EGFRs into
      intracellular vesicles that can not be blocked with an antagonistic antibody. The
      net result is a decrease in the level of cell-surface EGFRs available for ligand
      stimulation. Thus, rab5 activation regulates EGFR signaling by facilitating the
      internalization of the unliganded EGFR.

PMID- 15260831
TI  - Targeting of proteins derived from self-processing polyproteins containing
      multiple signal sequences.
AB  - The 18aa 2A self-cleaving oligopeptide from foot-and-mouth disease virus can be
      used for co-expression of multiple, discrete proteins from a single ORF. 2A
      mediates a co-translational cleavage at its own C-terminus and is proposed to
      manipulate the ribosome into skipping the synthesis of a specific peptide bond
      (producing a discontinuity in the peptide backbone), rather than being involved
      in proteolysis. To explore the utility of the system to target discrete
      processing products, self-processing polyproteins comprising fluorescent proteins
      flanking 2A were constructed, permutating both the type of signal sequence and
      the location within the polyprotein. A polyprotein comprising a protein bearing
      an N-terminal signal sequence, 2A, then a protein lacking any signal sequence,
      was constructed. Interestingly, both proteins were translocated into the
      endoplasmic reticulum. Despite the discontinuity in the peptide backbone, the
      mammalian ribosome:translocon complex did not disassemble--the second protein
      (lacking any signal) 'slipstreamed' through the translocon formed by the first
      (signal-bearing) protein. These polyprotein systems provide a novel method of
      targeting proteins to different subcellular sites by transfection with a plasmid
      encoding a single ORF. The inclusion of a fluorescent reporter enables
      visualisation of expression levels, whilst inclusion of a selectable marker
      enables stable cell-lines to be established rapidly.

PMID- 15260832
TI  - Prointegrin maturation follows rapid trafficking and processing of MT1-MMP in
      Furin-Negative Colon Carcinoma LoVo Cells.
AB  - Understanding the function of invasion-promoting membrane type-1 matrix
      metalloproteinase (MT1-MMP) is of paramount importance for understanding cancer
      biology. MT1-MMP is synthesized in cells as a latent zymogen that requires the
      cleavage of its prodomain to exert the proteolytic activity. The mature alphav
      integrin subunit is also generated by endoproteolytic cleavage of the alphav
      subunit precursor (pro-alphav). Cleavage by furin is considered to be a principal
      event in the activation of both MT1-MMP and pro-alphav. To elucidate the
      alternative activation pathway of MT1-MMP and pro-alphav, we employed furin
      negative LoVo cells, which co-express MT1-MMP with integrin alphavbeta3. In these
      cells the MT1-MMP proenzyme was rapidly trafficked to the plasma membrane via an
      unconventional Brefeldin A-resistant pathway and, then, autocatalytically
      processed on the cell surface. Next, the MT1-MMP activity converted the cell
      surface-associated pro-alphav into the mature alphav integrin, represented by the
      disulfide-bonded heavy and light chains, and promoted the formation of the
      functional integrin alphavbeta3 heterodimer. These events stimulated cell
      motility in vitro, and malignant invasion and tumor growth in vivo. Our data
      suggest that in furin-negative colon carcinoma cells MT1-MMP is autocatalytically
      processed and the active protease then operates as a prointegrin convertase. Our
      findings argue strongly that the processing by furin is not a prerequisite for
      the activation of MT1-MMP.

PMID- 15260833
TI  - Prescription for a healthy future.

PMID- 15260834
TI  - An evaluation of a volunteer-support program for families at risk.
AB  - A descriptive comparative design was used to evaluate the Cottage Community Care
      Pilot Project, a family support/child protection initiative linking trained
      volunteers with "vulnerable" first-time parents. Fifty-eight eligible and
      consenting families enrolled in the program and formed the intervention group. A
      further 35 eligible families consented to participate in the evaluation and
      received assessments only and formed the comparison group. No differences were
      evident between the intervention and comparison groups on parenting readiness.
      For the intervention group (n = 25), improvements occurred in seven aspects of
      family functioning (items on the Scale of Family Functioning) when contrasted to
      the comparison group (n = 24). Two areas of family functioning were found to be
      statistically significant: access to social support (p = 0.02) and age
      appropriate expectations of infants (p < 0.001). Participants reported
      satisfaction with the program, and the study emphasized the need to include all
      families, not just those at risk. This evaluation supports the continued
      development of volunteer-support programs and the active role that public health
      nurses play in the growth and development of children in our communities.

PMID- 15260835
TI  - Evaluating the needs of children with asthma in home care: the vital role of
      nurses as caregivers and educators.
AB  - To date, few evaluations have examined issues specific to children's asthma
      management in their homes. This study examined the characteristics, risk factors,
      and needs of children with asthma, and the impact of home health nurses on
      improving parents'/family caregivers' knowledge about asthma triggers and
      management. The medical records of children, </=19 years, residing in New York
      City, who were admitted to home care with asthma in 1999 (n = 1,007) were
      reviewed retrospectively to collect a wide range of data. The majority of
      children with asthma in home care were </=5 years, male, racial/ethnic
      minorities, and hospital referred. Approximately one in four children with asthma
      suffered from additional comorbidities. Home environmental triggers included
      dust/dust mites, animal dander, mold, perfumes/detergents, and cigarette smoke.
      Notable psychosocial triggers were family tensions, physical activity,
      anxiety/stress, and friends/peer pressure. Most parents/family caregivers had
      inadequate knowledge about recognition of asthma attacks and its triggers and
      management. Discharge assessments suggested that home health nurses can help
      improve caregivers' knowledge about asthma management. Children with asthma in
      home care have diverse needs, receive few nurse home visits, and have
      parents/family caregivers in need of more intensive education on asthma symptom
      recognition and management.

PMID- 15260836
TI  - School-based youth health nurses: roles, responsibilities, challenges, and
      rewards.
AB  - A case study and focus-group discussions were conducted with 10 youth health
      nurses (nurses) employed in the recently introduced School-Based Youth Health
      Nurse Program (SBYHNP) to identify their roles, responsibilities, and
      professional development needs. Major roles are support, referral, health
      promotion, and marketing. Clients include high school students, teachers, and
      parents; the majority of whom are female and aged 13-16 years. Health issues
      addressed during individual consultations are predominantly psychosocial but also
      include medical, sexual health and sexuality issues, health surveillance, and
      risk-taking behaviors. Nurses also provide clients with health information and
      promote enhanced personal skill development during these consultations. Health
      promotion strategies undertaken by nurses were predominantly health education and
      health information displays. Nurses reported marketing their role and function
      within the school to be an essential and often difficult aspect of their role.
      Professional development through the SBYHNP was excellent; however, there was
      concern relating to the availability of future educational opportunities. The
      SBYHNP provides nurses with a new, challenging, autonomous role within the school
      environment and the opportunity to expand their role to incorporate all aspects
      of the health-promoting schools' framework.

PMID- 15260837
TI  - Collaboration between nurses and agricultural teachers to prevent adolescent
      agricultural injuries: the Agricultural Disability Awareness and Risk Education
      Model.
AB  - Nearly 2 million children live or work on America's farms and ranches. Despite
      the increasing mechanization of production agriculture in the United States,
      children still constitute a considerable portion of the work force on farms and
      ranches. When adjusted for actual work exposure time, adolescent injury rates on
      agricultural establishments surpass those of adults (Castillo, D. N., Landen, D.
      D., & Layne, L. A. (1994). American Journal of Public Health, 84, 646-649). This
      project, headed by two public health nurses, developed and tested an agricultural
      safety curriculum [Agricultural Disability Awareness and Risk Education (AgDARE)]
      for use in high school agriculture classes. Students who participated in AgDARE
      scored significantly higher in farm safety attitude and intent to change work
      behavior than the control group. School and public health nurses, working
      together with agriculture teachers, may make an effective team in reducing
      injuries among teen agricultural workers.

PMID- 15260838
TI  - The Baby Think It Over experience to prevent teen pregnancy: a postintervention
      evaluation.
AB  - An evaluation was conducted to describe the personal impact of the "In Your Care"
      pregnancy prevention intervention program using Baby Think It Over infant
      simulator. Data was collected regarding the attitudes, actual and intended sexual
      practices, feelings, and opinions of participants 2 or 3 years after the
      intervention. Student recommendations for program continuation and improvement
      were also solicited. Male and female 11(th) grade students in rural and suburban
      Midwestern communities, who had experienced the program 2 or 3 years earlier,
      completed surveys and were interviewed in focus groups. Participants vividly
      recalled and described the simulated experience in statements that reflected
      insight and feelings about parental responsibility and the consequences of teen
      pregnancy. The teens also made several recommendations for enhancing the program.
      The findings suggest that simulated experiences can be a powerful strategy for
      effective learning about complex decisions regarding the risks of sexual activity
      and the realities of parenting.

PMID- 15260839
TI  - Personal narratives of adolescent mothers-to-be: contraception, decision making,
      and future expectations.
AB  - Results not discussed in a previously published qualitative study (Spear, 2001)
      are presented in this article. Analysis of the personal narratives of eight
      pregnant adolescents who attended an alternative school for pregnant teens
      yielded the following categories: decision making, contraceptive behavior and
      sexual attitudes, and future expectations. The findings revealed that decisions
      regarding pregnancy were made with little deliberation and some participants
      implied that pregnancy was planned. Although knowledgeable about how to prevent
      pregnancy, participants did not consistently practice contraception and their
      sexual experiences were marked by indifference and lacked intimacy. Future
      expectations consistently included support from the fathers of their unborn
      children. Implications for nursing practice and further research are discussed.

PMID- 15260840
TI  - Family matters: how mothers of adolescent parents experience adolescent pregnancy
      and parenting.
AB  - Family support has been demonstrated to be essential for successful long-term
      outcomes of low-income, African American adolescent mothers and their children
      [Apfel, N., & Seitz, V. (1996). Urban girls: Resisting stereotypes, creating
      identities. NY: New York University Press]. Family support may also be essential
      for the continued paternal involvement of unmarried, low-income, African American
      adolescent fathers. Twenty mothers of unmarried, low-income, African American
      adolescent parents were individually interviewed for this qualitative study to
      describe the experiences of paternal grandmothers (mothers of adolescent fathers)
      and maternal grandmothers (mothers of adolescent mothers) during transition to
      fatherhood for unmarried, low-income, African American adolescent fathers.
      Findings are presented according to the six factors of transition conditions from
      the nursing model of transitions [Schumacher, K., & Meleis, A. I. (1994). Image,
      26, 119-127]: meanings, expectations, level of knowledge and skill, the
      environment, level of planning, and emotional and physical well-being. Findings
      indicate that transition to parenthood and grandparenthood is often abrupt and
      complicated for unmarried, low-income, African American adolescent parents and
      their families. Paternal and maternal grandmothers continue to act as primary
      parents for their adolescents while compensating for the lack of skills and
      attributes for the adolescents' children. Findings from this study can be used to
      design developmentally and culturally appropriate health care interventions that
      can support these families during this complex process.

PMID- 15260841
TI  - Development of a student nurses' clinic for homeless men.
AB  - A nursing clinic for homeless men was developed by a faculty member and her
      senior community health nursing students in a city mission over a 2.5-year
      period. The development of this clinic and a conceptualization of their nursing
      roles are described. Nursing care focused on promoting access to primary care
      through screening and referral and through nursing interventions of education,
      counseling, advocacy, and collaboration. Because the Student Nurses' Clinic was
      instrumental in clarifying and conceptualizing what nurses can do to promote
      primary care, mission administrators and staff gained insights about nursing and
      are better prepared to plan programs for the health care needs of the homeless
      men-the "guests" at the mission.

PMID- 15260842
TI  - Comparisons of motivation, health behaviors, and functional status among elders
      in residential homes in Korea.
AB  - This study compared the changes in health behaviors, motivation, and functional
      status between motivation enhancement exercise-program participants and program
      dropouts over 6 months. A total of 73 older adults living in residential homes
      participated in the study. Face-to-face interviews were conducted at pretest and
      then at 10 weeks and 6 months in the program. The participants exercised using
      traditional Korean dance movements for 50 min, 4 times per week, for 6 months.
      The subjects were classified as participants or dropouts by using a cutoff
      attendance rate of 80%. Repeated ANOVA revealed the following results over 6
      months: 1 The motivation to perform health behaviors, especially for perceived
      benefits, improved significantly for the participants than for the dropouts. 2
      Significant differences in the performance of overall health behaviors and
      exercise-related behaviors were found between the participants and the dropouts.
      3 The sickness impact profile (SIP) of the participants improved significantly,
      compared with the dropouts. Significant group differences were found for total
      SIP, physical dimensions, and enjoyment of recreation and pastimes. In
      conclusion, the study found that the 6-month motivation enhancement program was
      effective in motivating older adults to perform health behaviors and to improve
      their functional status.

PMID- 15260843
TI  - The Black-White perception gap and health disparities research.
AB  - Reducing and eliminating racial and ethnic health disparities has become a
      national research priority. This research agenda requires new research frameworks
      that encompass the social determinants of health and the translation pathways of
      these social contexts into physiological morbidity. Within these sociobiological
      research frameworks, identity and emotions are seen as crucial links in the
      causal pathways from stressors to biological responses. In this country, the
      lived social reality of African American individuals is experienced through the
      color of their skin. Their identity is bound with the racial inequities of our
      society. It has been suggested that the emotions of anger and frustration
      resulting from this institutionalized racial discrimination are an emotional
      causative pathway to the pathophysiology contributing to the health disparities
      experienced by African Americans. However, as much as we espouse the concept of
      cultural competency in health care, until recently, there has been very little
      honest dialogue about how race and racism influences health. This article will
      explore the Black-White cultural perception gap and attempt to provide insight on
      the relationship to African American health and implications for health
      disparities research.

PMID- 15260844
TI  - From miasma to fractals: the epidemiology revolution and public health nursing.
AB  - If public health nursing is truly a synthesis of public health science and
      nursing science, then nurses must keep track of current developments in public
      health science. Unfortunately, the public health nursing literature has not kept
      pace with revolutionary developments in epidemiology, one of the sciences that
      informs population-focused nursing practice. Most epidemiology chapters in
      community health nursing texts do not reflect the intellectual development that
      has taken place in epidemiology over the past two decades. The purpose of this
      article therefore is to facilitate an updated synthesis by (a) reviewing the
      development of epidemiology and the focus of public health nursing practice
      through three historical eras, (b) discussing current controversies and tensions
      within epidemiology, (c) introducing an emerging paradigm in epidemiology based
      on an ecosocial perspective, and (d) discussing the congruence of this
      perspective with the evolving theory and practice of public health nursing.

PMID- 15260845
TI  - Aberrant methylation of p14(ARF), p15(INK4b) and p16(INK4a) genes and location of
      the primary site in pulmonary squamous cell carcinoma.
AB  - Aberrant methylation of cytosines in CpG islands of the promoter regions of tumor
      suppressor genes is found in human tumors as a common mechanism of gene
      silencing. We investigated the methylation status of the chromosome 9p21 gene
      cluster (p14(ARF), p15(INK4b) and p16(INK4a) genes) by methylation-specific
      polymerase chain reaction in 20 central and 40 peripheral types of pulmonary
      squamous cell carcinoma (SqCC) in order to determine the differences between the
      pathogeneses of the central and peripheral types of SqCC. The frequencies of
      methylation were 30% for the p14(ARF) gene, 20% for the p15(INK4b) gene and 40%
      for the p16(INK4a) gene in the central type and 25% for the p14(ARF) gene, 10%
      for the p15(INK4b) gene and 38% for the p16(INK4a) gene in the peripheral type.
      Cases in which there was methylation of the p16(INK4a) gene had a higher smoking
      index in the peripheral type (P = 0.007). This trend was not detected in the
      central type. Methylation of two or three genes was observed in 55% of
      methylation in at least one gene of the central type but in only 17% of the
      peripheral type. This overlap methylation of the chromosome 9p21 gene cluster was
      found more frequently in the central type (P = 0.02). These findings suggest one
      of the epigenetic differences between the central and peripheral types of SqCC.

PMID- 15260846
TI  - Coexpression of heparanase, basic fibroblast growth factor and vascular
      endothelial growth factor in human esophageal carcinomas.
AB  - Heparan sulfate (HS), which is degraded by heparanase, plays an important role in
      cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir
      for various growth factors such as basic fibroblast growth factor (bFGF) and
      vascular endothelial growth factor (VEGF). In the present study, we examined the
      immunohistochemical expression of heparanase, bFGF and VEGF, and evaluated the
      correlation between their expression and microvessel density (MVD) in human
      esophageal carcinomas. Heparanase, bFGF and VEGF were immunolocalized
      predominantly to the carcinoma cells, but they were also localized to the
      endothelial cells of microvessels near the carcinoma cell nests. In carcinomas
      with invasion of the muscular layer or adventitia, heparanase staining was
      stronger at the invasive areas of carcinomas than the intraepithelial spread.
      Expression of heparanase and bFGF and the degree of MVD were associated with
      tumor invasion, lymph node metastasis and pathological stages. Cases with
      positive staining for heparanase, bFGF or VEGF tended to have a higher MVD than
      those without staining, and carcinomas with concomitant expression of heparanase,
      bFGF and VEGF showed the highest MVD. The level of heparanase mRNA expression was
      directly correlated with the MVD. In addition, heparanase-positive cases had a
      higher positive ratio of bFGF and VEGF compared with the heparanase-negative
      cases. These data suggest the possibility that heparanase may contribute to not
      only cancer cell invasion but also angiogenesis probably through degradation of
      HS in the ECM and release of bFGF and VEGF from the HS-containing ECM.

PMID- 15260847
TI  - Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin
      dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative
      chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator
      of chemosensitivity to 5-fluorouracil.
AB  - High expression of thymidylate synthase (TS) is allegedly associated with the
      chemoresistance to 5-fluorouracil (5-FU) in colorectal cancers. However, low TS
      expression does not necessarily imply chemosensitivity. Inactivation of
      p16(INK4a) correlates with poor prognosis in various cancers. We
      immunohistochemically evaluated the relationship between the expression of TS,
      p16(INK4a), CDK4 and cyclin D1 and the effect of 5-FU-based chemotherapy in
      colorectal cancers. After antigen retrieval, immunoperoxidase staining was
      performed on the paraffin-embedded, biopsy and surgical specimens of 37 advanced
      colorectal cancers preoperatively treated with peroral administration of 5-FU
      derivatives. As a control group, 31 colorectal cancers without preoperative
      treatment were analyzed. High TS expression was found in 23 (74%) of 31 tumors
      resected from histological non-responders and in 19 (61%) of 31 controls but in
      none of six responders. High p16(INK4a) expression was seen in 83% of the
      responders, 52% of the non-responders and 32% of the controls. The TS
      low/p16(INK4a)-high phenotype was noted in 83% of the responders, but only in 3%
      of the non-responders (P = 0.0001). Induction of p16(INK4a) expression after
      chemotherapy was predominantly seen in the responders. Neither CDK4 nor cyclin D1
      expression was related to the chemotherapeutic effects. In conclusion, the
      combination of low expression of TS and induction of p16(INK4a) after
      chemotherapy can be important indicators of the sensitivity to 5-FU-based
      chemotherapy in colorectal cancers.

PMID- 15260848
TI  - Phenotypic alterations of mucins and cytokeratins during gallbladder
      carcinogenesis.
AB  - In order to evaluate the significance of altered expression of mucin and
      cytokeratin during gallbladder carcinogenesis, we characterized the expressional
      profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31
      adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal
      gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1
      expression was absent. However, in adenomas, dysplasias and carcinomas, the
      expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was
      elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder
      epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently
      associated with carcinomas and showed a higher grade of atypia than those without
      these antigens. In carcinomas, MUC1 expression was related to invasive growth,
      lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was
      related to non-invasive growth. CK7 was diffusely expressed in almost all
      lesions, but carcinomas with a loss of CK7 expression showed poor survival. In
      conclusion, normal gallbladder mucosa has a gastric phenotype, but during
      carcinogenesis and tumor progression, the gastric phenotype is gradually lost and
      the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in
      the gallbladder.

PMID- 15260849
TI  - Mechanism of transepithelial elimination of elastic fibers in keratoacanthoma.
AB  - Transepithelial elimination of elastic fibers is frequently seen in
      keratoacanthoma. However, the mechanism underlying this elastic fiber transport
      is not yet fully understood. We investigated the process by comparing the related
      features of 27 cases of keratoacanthoma, eight cases of squamous cell carcinoma
      and 11 cases of seborrheic keratosis (control). Microscopically, transepithelial
      elimination of elastic fibers was specifically observed in keratoacanthomas.
      Elastic fibers were surrounded by keratoacanthoma cell membrane and were
      ultrastructurally associated with hemidesmosomes and the basement membrane.
      Collagen fibrils were also observed within small, membrane-delineated vesicles
      within cells in the lower layers of the tumor. Also noted was strong expression
      of matrix metalloproteinase-1, which was detected by immunohistochemical analysis
      and in situ hybridization. Western blotting showed significantly stronger
      labeling of matrix metalloproteinase-1 in samples of keratoacanthoma than in
      normal epidermis. In contrast, squamous cell carcinomas and seborrheic keratosis
      exhibited none of the aforementioned characteristics. We propose that
      keratoacanthoma cells entrap, lift and eliminate elastic fibers as they
      proliferate and keratinize toward the epidermal surface, while simultaneously
      phagocytosing collagen fibrils. In that regard, matrix metalloproteinase-1
      appears to play a key role in the degradation of collagen fibrils.

PMID- 15260850
TI  - Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic
      and neoplastic breast lesions, with particular reference to early carcinogenesis.
AB  - In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in
      breast carcinogenesis, we have studied the expression of 14-3-3sigma
      immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ
      (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for
      estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger
      protein (Efp) was also carried out. Immunohistochemically, expression of 14-3
      3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to
      23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to
      IDC, while p53 showed an inverse staining pattern to that of ERalpha. The
      expression of Efp showed no significant difference among the three breast
      lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a
      tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis
      was then carried out on columnar cell hyperplasia with atypia (CCHA), in which
      the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested
      that it might be possible that CCHA is a precancerous lesion.

PMID- 15260851
TI  - Oncocytic adrenocortical carcinomas: a pathological and immunohistochemical study
      of four cases in comparison with conventional adrenocortical carcinomas.
AB  - Clinicopathological features of four cases of oncocytic adrenocortical carcinomas
      were studied. All tumors were large, circumscribed tumors with average size and
      weight of 11.5 cm and 586 g, respectively. The cut surfaces were yellow or brown
      and tan with areas of hemorrhage, necrosis, fibrosis, myxoid and cystic change.
      The tumor cells were exclusively oncocytic with a diffuse or compact and solid
      arrangement. Nuclear atypia was identified but mitosis was rare. Capsular
      invasion was identified in all tumors and vascular invasion was identified in one
      tumor. All tumors were immunoreactive for vimentin and inhibins. Immunoreactivity
      for pancytokeratin, synaptophysin and S-100 protein was variable and focal. All
      tumors had low proliferative indices, of less than 1%, and were negative for p53
      protein. Ultrastructurally, the cytoplasm of tumor cells showed numerous
      mitochondria in a compact arrangement. Oncocytic adrenocortical carcinomas showed
      a similar sex ratio, slightly older mean age, similar left predilection, slightly
      smaller size and lighter weight compared with the conventional carcinomas. We
      suggest that most oncocytic adrenocortical carcinomas might be low-grade
      malignancies with less aggressive histological features compared with
      conventional carcinomas. However, they should be excised completely because of
      the likelihood of recurrence and metastasis during the follow-up period.

PMID- 15260852
TI  - Pulmonary synovial sarcoma with polypoid endobronchial growth: a case report,
      immunohistochemical and cytogenetic study.
AB  - A rare case of primary pulmonary synovial sarcoma with polypoid endobronchial
      growth in a 42-year-old Japanese woman is described. Left upper sleeve lobectomy
      was performed for the polypoid tumor measuring 2.5 cm in the left major bronchus
      and the patient was treated with adjuvant chemotherapy. Three years later, a
      recurrent tumor was discovered. Microscopically, this tumor was characterized by
      a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles
      and covered by the thin normal bronchial epithelium. Immunohistochemically, tumor
      cells were positive for vimentin, and focally positive for pancytokeratin
      recognized by AE1/AE3, cytokeratin 7 and epithelial membrane antigen. A chimera
      gene, SYT-SSX1, was detected. Recently, primary pulmonary synovial sarcoma is an
      increasingly recognized clinical entity; however, most of these tumors present as
      a parenchymal mass. The present case is a unique example of primary synovial
      sarcoma of endobronchial polypoid type. This case suggests that pulmonary
      synovial sarcoma might originate from bronchial submucosal stromal tissue.

PMID- 15260853
TI  - Proximal-type epithelioid sarcoma in a 36-year-old man: closer immunoelectron
      microscopic resemblance of the tumor cells to epithelial cells than to
      mesenchymal cells.
AB  - Proximal-type epithelioid sarcoma (PES) is a rare neoplasm. We report a case of
      PES that arose in the perineal subcutis of a 36-year-old Japanese man who died
      within 4 months of the first clinical sign, probably due to massive pulmonary
      metastases. In the present study, we analyzed the tumor obtained at surgery,
      immunohistochemically, immunoelectron-microscopically and genetically. Although
      the tumor cells in the patient expressed both cytokeratin and vimentin
      immunohistochemically, they showed epithelial characteristics immunoelectron
      microscopically because they had tonofilaments constructed of cytokeratin, not
      vimentin. In addition, the cytokeratins expressed on the tumor were glandular
      type keratins. These findings indicate that PES may be a form of carcinoma in
      soft tissue. To ascertain the possible origin of the tumor, we compared the tumor
      immunohistochemically with fetal tissues. Although notochord and fetal peritoneal
      mesothelium were similar to the tumor antigenically, we could not confirm the
      specific origin of the tumor. Furthermore, the p53-WAF1 pathway did not
      contribute to tumorigenesis in the patient because the tumor had no mutation in
      exons 5-8 of the p53 gene and was immunohistochemically positive for WAF1.

PMID- 15260854
TI  - Malignant rhabdoid tumor of the liver: case report and literature review.
AB  - A case of malignant rhabdoid tumor (MRT) occurring as a primary hepatic neoplasm
      in a 12-month-old Japanese female infant is presented. The patient had a slight
      fever for 2 weeks and presented with a palpable mass in her left hypochondrial
      region. After admission, the hepatic artery was embolized due to intra-abdominal
      hemorrhage arising from the tumor. The patient received chemotherapy with
      cisplatin, cyclophosphamide and adriacin. Despite treatment, the patient
      developed dyspnea, pancytopenia and disseminated intravascular coagulation.
      Rupture of the tumor resulted in death within 3 weeks. A limited abdominal
      autopsy revealed that the liver weighed 1240 g and was occupied by multiple
      hemorrhagic and/or necrotic tumor nodules. Histologically, neoplastic cells had
      an abundant eosinophilic cytoplasm containing paranuclear inclusions, and
      vesicular nuclei with a centrally located prominent nucleolus. Ultrastructurally,
      the cytoplasmic inclusions were composed of whorled filaments measuring 10 nm.
      Immunohistochemically, almost all of the neoplastic cells were positive for
      vimentin and cytokeratins (CK) 8 and 18, some were positive for CK 7 and 19,
      while none were positive for CK 1, 10, 13-17 and 20. The tumor cells did not
      express desmin, myoglobin, and alpha-fetoprotein. We found 18 cases of MRT of the
      liver published in English language literature and then, adding the present case,
      we summarized the 19 cases. Hepatic MRT is an uncommon neoplasm. However, it
      should be considered in the differential diagnosis of an aggressive liver
      neoplasm in childhood.

PMID- 15260855
TI  - Anal canal neuroendocrine carcinoma with Pagetoid extension.
AB  - A case of anal canal neuroendocrine carcinoma with Pagetoid intraepithelial
      extension is presented. An 80-year-old man was admitted to hospital with a
      complaint of pain in the anorectal region. Clinical examination revealed a hard
      and fixed mass in the anal canal, and subsequent biopsy of the lesion showed it
      to be a carcinoma. The surgically resected specimen showed a solid tumor
      measuring 3.4 x 3.2 cm within the area from the surgical anal canal to the
      anatomical anal canal. Tumor cells proliferated predominantly with compact nests.
      Many tumor cells had a high nuclear-to-cytoplasmic ratio, dispersed chromatin,
      and conspicuous nucleoli. Additionally, neoplastic cells focally formed a
      glandular structure. Some polygonal neoplastic cells were small with round
      nuclei. A rosette-like arrangement was also focally observed. In addition, tumor
      cells exhibited Pagetoid extension into the overlying epithelium of the
      histological anal canal. Both the underlying original neoplastic cells and the
      Pagetoid spreading tumor cells showed cytoplasmic granules positive for Grimelius
      staining and immunopositivity for carcinoembryonic antigen, synaptophysin and
      cytokeratins 7 and 20. These findings are highly suggestive of neuroendocrine
      differentiation of adenocarcinoma cells. To the best of our knowledge, this is
      the first case of anal canal neuroendocrine carcinoma with Pagetoid extension
      into the overlying epithelium of the histological anal canal.

PMID- 15260856
TI  - Systemic granulomatous necrotizing vasculitis in a MPO-ANCA-positive patient.
AB  - We present a case of myeloperoxidase antineutrophil cytoplasmic antibody (MPO
      ANCA)-associated vasculitis that demonstrated a systemic granulomatous lesion at
      autopsy. The patient initially showed anorexia, general malaise and anemia. Colon
      fiber was examined to detect the bleeding site, which revealed ischemic mucosal
      damage associated with venous fibrin thrombus. Because a high titer of MPO-ANCA
      was found, ANCA-associated vasculitis was suspected and the patient was started
      on steroid pulse therapy. However, anemia, renal failure and respiratory failure
      worsened and the patient died of sudden cardiac failure 2 days after the start of
      the therapy. An autopsy revealed systemic arteritis in multiple organs including
      the kidneys, liver, spleen, gastrointestinal system and genital organs that
      indicated fibrinoid necrosis accompanied by granulomatous reaction with
      multinucleated giant cells; the granulomatous reaction further extended along the
      splenic capsule. Glomerulonephritis and diffuse pulmonary damage, which are
      common in MPO-ANCA-associated vasculitis, were almost absent but parapleural
      fibrosis was present. The direct cause of death was presumed to be hemorrhagic
      shock due to rupture of an aneurysm in the gastric subserosa. As far as we know,
      this is the first case of a systemic granulomatous reaction in MPO-ANCA-positive
      vasculitis, although the cause of the granulomatous lesion is unknown.

PMID- 15260857
TI  - Clear cell adenocarcinoma of the tunica vaginalis of the testis with an adjacent
      uterus-like tissue.
AB  - Testicular and paratesticular neoplasms that resemble the common epithelial type
      of ovarian tumor are quite rare. Paratesticular clear cell carcinoma is very
      uncommon in the testis, with no reported cases of a tumor arising from the tunica
      vaginalis in the literature to our knowledge. The present case shows that it is
      highly malignant and metastatic. The differential diagnosis of the tumor was made
      after thorough clinical, pathological and immunohistochemical investigations,
      from the mesothelioma of the tunica vaginalis, paratesticular serous papillary
      carcinoma, carcinoma of the rete testis, epididymal adenocarcioma, yolk sac tumor
      of the testis and metastatic carcinoma. The tumor showed Bcl-2 and Her-2/neu
      immunoreactivity, but was non-reactive for p53. This tumor, with a uterus-like
      structure as a paratesticular tumor-like mass, was composed of endometrial-type
      glands and stroma surrounded by bundles of smooth muscle, and is the third
      example of this kind of structure in English written literature. The patient,
      having normal external genitalia and fertility, represents the first reported
      case of paratesticular malignant differentiation of mullerian-type epithelium in
      the normal gonadal state. Mullerian-type epithelium located in the vicinity of
      the testis and/or endometriotic metaplasia of the mesothelium of the tunica
      vaginalis might be the possible origins for this uterus-like structure, and as a
      result, for this tumor.

PMID- 15260859
TI  - Aggression and moral development: integrating social information processing and
      moral domain models.
AB  - Social information processing and moral domain theories have developed in
      relative isolation from each other despite their common focus on intentional harm
      and victimization, and mutual emphasis on social cognitive processes in
      explaining aggressive, morally relevant behaviors. This article presents a
      selective summary of these literatures with the goal of showing how they can be
      integrated into a single, coherent model. An essential aspect of this integration
      is Crick and Dodge's (1994) distinction between latent mental structures and
      online processing. It is argued that moral domain theory is relevant for
      describing underlying mental structures regarding the nature and boundaries of
      what is moral, whereas the social information processing model describes the
      online information processing that affects application of moral structures during
      peer interactions.

PMID- 15260860
TI  - Returning to roots: on social information processing and moral development.
AB  - Social information processing theory has been posited as a description of how
      mental operations affect behavioral responding in social situations. Arsenio and
      Lemerise (this issue) proposed that consideration of concepts and methods from
      moral domain models could enhance this description. This paper agrees with their
      proposition, although it suggests that numerous additional concepts about the
      nature of latent mental structures (e.g., working models, schemas, scripts,
      object relations, classical conditioning) provide equally compelling refinements
      to processing theory. Furthermore, theoretical and methodological challenges in
      integrating latent mental structures into processing theory remain.

PMID- 15260861
TI  - Finding commonalities: social information processing and domain theory in the
      study of aggression.
AB  - The Arsenio and Lemerise (this issue) proposal integrating social information
      processing (SIP) and domain theory to study children's aggression is evaluated
      from a domain theory perspective. Basic tenets of domain theory rendering it
      compatible with SIP are discussed as well as points of divergence. Focus is
      directed to the proposition that domains constitute latent structures of SIP.
      Latent structures are described as cogenerative elements of online processing
      rather than cumulative stores of social information. Microgenetic studies of the
      reciprocal role of productive systems described within SIP and latent structures
      attributed to domain theory are proposed as important to the study of children'
      aggression. Domain theory studies of social exclusion and bullying are proposed
      as rich contexts for future research.

PMID- 15260862
TI  - Extended households and the life course of young mothers: understanding the
      associations using a sample of mothers with premature, low birth weight babies.
AB  - This paper examined whether the greater average schooling and employment, and
      lower parenting competence, of young mothers who reside with adult relatives
      reflect preexisting differences versus potential causal mechanisms. The sample
      included 554 young mothers (ages 13 to 25; nearly two thirds African American)
      from the Infant Health and Development Program (IHDP) a random-assignment
      intervention study of premature, low birth weight babies followed 8 times from
      birth to age 3. Ordinary least squares, fixed-effects, and random-effects models
      indicated that young mothers of low birth weight babies sorted into extended
      households based on preexisting characteristics that were correlated with their
      lower parenting skills and knowledge. In contrast, coresidence predicted greater
      schooling or employment across models, with some variations for different
      subgroups.

PMID- 15260863
TI  - Socioeconomic status and health in adolescents: the role of stress
      interpretations.
AB  - The role of psychological interpretations in the relationship between low
      socioeconomic status (SES) and physiological responses was tested. One hundred
      high school students (ages 15-19) watched videos of ambiguous and negative life
      situations, and were interviewed about their interpretations. Lower SES was
      associated with greater threat interpretations during ambiguous (but not
      negative) situations and with greater diastolic blood pressure and heart rate
      reactivity. Threat interpretations partially mediated relationships between SES
      and reactivity. General life events (e.g., lack of positive life events), rather
      than specific life events (e.g., exposure to violence), partially explained the
      relationship between low SES and threat interpretations. Results suggest that the
      larger social environment helps explain how adolescents approach new social
      situations, which in turn has implications for adolescent physical health.

PMID- 15260864
TI  - Infant vocal-motor coordination: precursor to the gesture-speech system?
AB  - This study was designed to provide a general picture of infant vocal-motor
      coordination and test predictions generated by Iverson and Thelen's (1999) model
      of the development of the gesture-speech system. Forty-seven 6- to 9-month-old
      infants were videotaped with a primary caregiver during rattle and toy play.
      Results indicated an age-related increase in frequency of vocal-motor
      coordination, greater coordination with arm (specifically right arm) than leg or
      torso movements, and a temporal pattern similar to that in adult gesture-speech
      coproductions. Rhythmic vocalizations (consonant-vowel repetitions) were more
      likely to occur with than without rhythmic movement, and with rhythmic manual
      than with nonmanual activity, and the rate of vocal-manual coordination was
      higher in babblers than in prebabblers.

PMID- 15260866
TI  - High antenatal maternal anxiety is related to ADHD symptoms, externalizing
      problems, and anxiety in 8- and 9-year-olds.
AB  - Associations between antenatal maternal anxiety, measured with the State Trait
      Anxiety Inventory, and disorders in 8- and 9-year-olds were studied prospectively
      in 71 normal mothers and their 72 firstborns. Clinical scales were completed by
      the mother, the child, the teacher, and an external observer. Hierarchical
      multiple regression analyses showed that maternal state anxiety during pregnancy
      explained 22%, 15%, and 9% of the variance in cross-situational attention deficit
      hyperactivity disorder symptoms, externalizing problems, and self-report anxiety,
      respectively, even after controlling for child's gender, parents' educational
      level, smoking during pregnancy, birth weight, and postnatal maternal anxiety.
      Anxiety at 12 to 22 weeks postmenstrual age turned out to be a significant
      independent predictor whereas anxiety at 32 to 40 weeks was not. Results are
      consistent with a fetal programming hypothesis.

PMID- 15260865
TI  - Speech perception in infancy predicts language development in the second year of
      life: a longitudinal study.
AB  - Infants' early phonetic perception is hypothesized to play an important role in
      language development. Previous studies have not assessed this potential link in
      the first 2 years of life. In this study, speech discrimination was measured in 6
      month-old infants using a conditioned head-turn task. At 13, 16, and 24 months of
      age, language development was assessed in these same children using the MacArthur
      Communicative Development Inventory. Results demonstrated significant
      correlations between speech perception at 6 months of age and later language
      (word understanding, word production, phrase understanding). The finding that
      speech perception performance at 6 months predicts language at 2 years supports
      the idea that phonetic perception may play an important role in language
      acquisition.

PMID- 15260867
TI  - Shape and the first hundred nouns.
AB  - This paper reports evidence from a longitudinal study in which children's
      attention to shape in a laboratory task of artificial noun learning was
      correlated with a rate shift in noun acquisitions. Eight children were tested in
      the laboratory at 3-week intervals beginning when they had less than 25 nouns in
      their productive vocabulary (M age=17 months). Children were presented with a
      novel word generalization task at each session. Additionally, the study examined
      the kinds of words the children learned early, based on parent reports, and the
      statistical regularities inherent in those vocabularies. The results indicate
      that as children learned nouns, they also learned to attend to shape in the novel
      word task. At the same time, children showed an acceleration in new noun
      production outside of the laboratory.

PMID- 15260868
TI  - Cross-linguistic analysis of vocabulary in young children: spanish, dutch,
      French, hebrew, italian, korean, and american english.
AB  - The composition of young children's vocabularies in 7 contrasting linguistic
      communities was investigated. Mothers of 269 twenty-month-olds in Argentina,
      Belgium, France, Israel, Italy, the Republic of Korea, and the United States
      completed comparable vocabulary checklists for their children. In each language
      and vocabulary size grouping (except for children just learning to talk),
      children's vocabularies contained relatively greater proportions of nouns than
      other word classes. Each word class was consistently positively correlated with
      every other class in each language and for children with smaller and larger
      vocabularies. Noun prevalence in the vocabularies of young children and the
      merits of several theories that may account for this pattern are discussed.

PMID- 15260869
TI  - Reciprocal influences among relational self-views, social disengagement, and peer
      stress during early adolescence.
AB  - This study examined reciprocal-influence models of the association between
      relational self-views and peer stress during early adolescence. The first model
      posited that adolescents with negative self-views disengage from peers, creating
      stress in their relationships. The second model posited that exposure to peer
      stress fosters social disengagement, which elicits negative self-views.
      Participants were 605 early adolescents (M age = 11.7). As part of a 3-wave
      longitudinal study adolescents reported on self-views and stress, and teachers
      reported on social disengagement. As hypothesized, negative self-views predicted
      social disengagement, which contributed to peer stress. Stress predicted
      subsequent disengagement and negative self-views. These findings suggest that
      adolescents and their environments participate in reciprocal-influence processes
      that account for cross-temporal continuity in personal attributes of youth and
      their social experiences.

PMID- 15260870
TI  - Relative roles of general and complementation language in theory-of-mind
      development: evidence from Cantonese and English.
AB  - Complex complements are clausal objects containing tensed verbs (e.g., that she
      cried) or infinitives (e.g., to cry), following main verbs of communication or
      mental activities (e.g., say, want). This research examined whether English- and
      Cantonese-speaking 4-year-olds' complement understanding uniquely predicts their
      representation of other minds (i.e., theory of mind). Results showed that neither
      meaning of main verbs (communication vs. desire) nor complement structure (tensed
      vs. infinitival) affected the correlation between complement understanding and
      theory of mind. More important, the correlation became insignificant after
      controlling for general language comprehension. These findings led to the
      conclusion that the syntax of complement per se does not contribute uniquely to
      theory-of-mind development; general language comprehension is a more important
      factor to consider.

PMID- 15260871
TI  - The development of symbol-infused joint engagement.
AB  - Fifty-six children were observed longitudinally from 18 to 30 months of age
      interacting with their mothers during a Communication Play that contained 8
      scenes designed to encourage interacting, requesting, commenting, and narrating.
      Of primary concern was how often symbols infused the child's states of engagement
      with people and objects and how experience in such symbol-infused states related
      to language acquisition. Findings indicate that symbols increasingly infuse joint
      engagement, and that both the timing and the trajectory vary widely among
      typically developing toddlers, especially during the last half of the 2nd year.
      Moreover, variations in amount of symbol-infused supported joint engagement may
      both be influenced by variations in the onset of language and contribute to
      differences in language facility at 30 months.

PMID- 15260872
TI  - Assessing attachment security with the Attachment Q Sort: meta-analytic evidence
      for the validity of the observer AQS.
AB  - The reliability and validity of the Attachment Q Sort (AQS; Waters & Deane, 1985)
      was tested in a series of meta-analyses on 139 studies with 13,835 children. The
      observer AQS security score showed convergent validity with Strange Situation
      procedure (SSP) security (r = .31) and excellent predictive validity with
      sensitivity measures (r = .39). Its association with temperament was weaker (r =
      .16), which supports the discriminant validity of the observer AQS. Studies on
      the stability of the observer AQS are still relatively scarce but they have
      yielded promising results (mean r = .28; k = 4, n = 162). It is concluded that
      the observer AQS, but not the self-reported AQS, is a valid measure of
      attachment.

PMID- 15260873
TI  - Factor structure of the pictorial scale of perceived competence and social
      acceptance with two pre-elementary samples.
AB  - Competing models of the factorial structure of the Pictorial Scale of Perceived
      Competence and Social Acceptance (PSPCSA) were tested for fit using multisample
      confirmatory factor analysis. The best fitting model was tested for invariance
      (a) across samples of middle-class (n = 251) and economically disadvantaged (Head
      Start, n = 117) kindergarten children (whose ages ranged from 67 to 86 months),
      and (b) over time (at the end of preschool and kindergarten) for the Head Start
      sample. For kindergarten children, regardless of socioeconomic status, the factor
      structure of the PSPCSA was consistent with the 2-factor model of Competence and
      Acceptance. This model also fit reasonably well for Head Start children at the
      end of their preschool year. However, in addition to providing broad support for
      the dimensionality of the measure, our findings highlight important concerns
      about the PSPCSA.

PMID- 15260874
TI  - Maternal parenting and children's conscience: early security as moderator.
AB  - Socialization research is shifting from direct links between parenting and
      children's outcomes toward models that consider parenting in the context of other
      factors. This study proposed that the effects of maternal responsive, gentle
      parenting on child conscience are moderated by the quality of their relationship,
      specifically, early security. A 2-process model of early conscience development
      was proposed and confirmed in this longitudinal study. The child's security and
      trust in the caregiver, assessed at 14 months in the Strange Situation, rendered
      him or her receptive and eager to accept the caregiver's socialization agenda.
      That early security then enhanced the effectiveness of parental adaptive
      parenting style, observed from 14 to 45 months, in terms of promoting conscience
      at 56 months, which encompassed moral conduct, moral cognition, and moral self.

PMID- 15260875
TI  - Children's perception of gap affordances: bicycling across traffic-filled
      intersections in an immersive virtual environment.
AB  - This study examined gap choices and crossing behavior in children and adults
      using an immersive, interactive bicycling simulator. Ten- and 12-year-olds and
      adults rode a bicycle mounted on a stationary trainer through a virtual
      environment consisting of a street with 6 intersections. Participants faced
      continuous cross traffic traveling at 25 mph or 35 mph and waited for gaps they
      judged were adequate for crossing. Children and adults chose the same size
      temporal gaps, but children left far less time to spare between themselves and
      the approaching vehicle when they crossed the intersection. Relative to adults,
      children delayed in getting started and took longer to reach the roadway.
      Discussion focuses on developmental changes in how children coordinate self
      movement with object movement.

PMID- 15260876
TI  - Maternal DHA and the development of attention in infancy and toddlerhood.
AB  - Infants were followed longitudinally to document the relationship between
      docosahexaenoic acid (DHA) levels and the development of attention. Erythrocyte
      (red-blood cell; RBC) phospholipid DHA (percentage of total fatty acids) was
      measured from infants and mothers at delivery. Infants were assessed in infant
      control habituation at 4, 6, and 8 months augmented with psychophysiological
      measures, and on free-play attention and distractibility paradigms at 12 and 18
      months. Infants whose mothers had high DHA at birth showed an accelerated decline
      in looking over the 1st year and increases in examining during single-object
      exploration and less distractibility in the 2nd year. These findings are
      consistent with evidence suggesting a link between DHA and cognitive development
      in infancy.

PMID- 15260877
TI  - General and task-related experiences affect early object interaction.
AB  - The effects of 2 weeks of no, general, and task-related enhanced movement
      experiences on 8- to 12-week-old infants' (N = 30) hand and foot interactions
      with objects were assessed using standard video and motion analysis. For hand
      object interaction ability, general and task experience led to greater success
      than did no experience, and task experience led to greater success than did
      general experience. Only general experience led to greater success for foot
      object interaction ability. Experiences therefore resulted in differential
      effects depending on which limbs infants used. The results suggest that different
      movement experiences can advance infants' earliest object interactions. They also
      indicate that even early purposeful behaviors result from a complex interplay of
      experience, current ability, and task demands.

PMID- 15260878
TI  - Prenatal cocaine exposure: a comparison of 2-year-old children in parental and
      nonparental care.
AB  - Effects of prenatal cocaine exposure and parental versus nonparental care on
      outcome at 2 years of age were examined. The sample included 83 cocaine-exposed
      and 63 nonexposed children and their caregivers; 49 and 34 of the cocaine-exposed
      children experienced parental and nonparental care, respectively. Prenatal drug
      exposure was not related directly to children's outcome at 2 years of age.
      However, compared with cocaine-exposed children in parental care, those in
      nonparental care experienced a more optimal environment and performed better in
      several developmental domains at 2 years of age in spite of being at greater
      neonatal risk. Further analyses suggested that this protective effect of
      nonparental care was in part due to nonkin rather than kin care.

PMID- 15260879
TI  - Effects on blood glucose, insulin, lipid and proatherosclerotic parameters in
      stable type 2 diabetic subjects during an oral fat challenge.
AB  - BACKGROUND: Restriction of fat intake has been effective in improving insulin
      sensitivity in obese and type 2 diabetic subjects, but what effects the
      recommended diet (less than 30% of total calories from fat) have not been
      elucidated in subjects with type 2 diabetes. The purpose of this study was to
      test the effects of oral fat challenge, composing 30% calories of a meal, on
      blood glucose, insulin, lipid, leptin, plasminogen activator inhibitor-1 (PAI-1)
      and tumor necrosis factor-alpha (TNF-alpha). DESIGN AND METHODS: Blood glucose,
      insulin, lipid, leptin, TNF-alpha and PAI-1 were compared in 14 type 2 diabetic
      patients and 10 normal subjects after an oral fat challenge upto 2 hours
      (fasting, 15 min, 30 min, 45 min, 60 min, 90 min and 120 min). RESULTS:
      Postprandial glucose, total cholesterol, leptin, PAI-1 levels did not differ
      significantly from levels at fasting. Serum triglyceride increased significantly
      from baseline only in diabetic patients (P = 0.042). Serum insulin increased
      postprandially in both groups (P = 0.028 in diabetic group and P = 0.055 in
      normal group), with displaying a prolonged insulin response in diabetic subjects.
      TNF-alpha decreased postprandially in both groups without significant difference,
      although diabetic patients have higher baseline levels (P = 0.024 compared to
      normal subjects). CONCLUSIONS: Oral fat load does not have an acute effect on
      blood glucose, total cholesterol, leptin and PAI-1 levels in both type 2 diabetic
      and normal subjects. TNF-alpha value showed decreased trend in both diabetic and
      normal subjects. The tendency of a delayed postprandial insulin response and
      elevated serum triglyceride level in diabetic subjects might be related to
      insulin resistance at the level of adipose tissue. Additional research is needed
      to assess the impact of the use of fat contents on the macronutrient composition
      of the diet, and potentially healthy and nutritional benefits for patients with
      diabetes.

PMID- 15260880
TI  - Heart rate analysis in normal subjects of various age groups.
AB  - BACKGROUND: Analysis of heart rate variation (HRV) has become a popular
      noninvasive tool for assessing the activities of the autonomic nervous system
      (ANS). HRV analysis is based on the concept that fast fluctuations may
      specifically reflect changes of sympathetic and vagal activity. It shows that the
      structure generating the signal is not simply linear, but also involves nonlinear
      contributions. Linear parameters, Power spectral indice (LF/HF) is calculated
      with nonlinear indices Poincare plot geometry(SD1,SD2), Approximate Entropy
      (ApEn), Largest Lyapunov Exponent (LLE) and Detrended Fluctuation Analysis(DFA).
      The results show that, with aging the heart rate variability decreases. In this
      work, the ranges of all linear and nonlinear parameters for four age group normal
      subjects are presented with an accuracy of more than 89%. As a pre-analysis step,
      the HRV data is tested for nonlinearity using surrogate data analysis and the
      results exhibited a significant difference in the ApEn, LLE, SD1/SD2 and DFA
      parameters of the actual data and the surrogate data. METHODS: The heart rate is
      analyzed using the various time domain parameters, frequency domain parameter and
      nonlinear parameters like Poincare geometry, ApEn, LLE and DFA. RESULTS: In this
      work, the different linear and nonlinear parameters evaluated show a particular
      range for various cardiac abnormalities. And the results of these were subjected
      to 't' test with more than 89% confidence interval giving excellent 'p' values in
      all cases. CONCLUSIONS: Heart rate variability (HRV) signal can be used as a
      reliable indicator of state of the heart. It becomes less random with the
      aging(less chaotic). This is evaluated by using various time domain, frequency
      domain and nonlinear parameters like SD1/SD2, ApEn, LLE alphas and alphal.
      Different ranges of non-linear parameters for various age groups are presented
      with 'p' value < or = 0.12.

PMID- 15260881
TI  - Mechanical properties of the porcine bile duct wall.
AB  - BACKGROUND AND AIM: The function of the common bile duct is to transport bile
      from the liver and the gall bladder to the duodenum. Since the bile duct is a
      distensible tube consisting mainly of connective tissue, it is important to
      obtain data on the passive mechanical wall properties. The aims of this study
      were to study morphometric and biomechanical wall properties during distension of
      the bile duct. METHODS: Ten normal porcine common bile ducts were examined in
      vitro. A computer-controlled volume ramp infusion system with concomitant
      pressure recordings was constructed. A video camera provided simultaneous
      measurement of outer dimensions of the common bile duct. Wall stresses and
      strains were computed. RESULTS: The common bile duct length increased by 25% from
      24.4 +/- 1.8 mm at zero pressure to 30.5 +/- 2.0 mm at 5 kPa (p < 0.01). The
      diameter increased less than 10% in the same pressure range from 8.6 +/- 0.4 mm
      to 9.3 +/- 0.4 mm (p < 0.01). The stress-strain relations showed an exponential
      behavior with a good fit to the equation: sigma = alpha x (exp(betaepsilon) - 1).
      The circumferential stress-strain curve was shifted to the left when compared to
      the longitudinal stress-strain curve, i.e. the linear constants (alpha values)
      were different (p < 0.01) whereas the exponential constants (beta values) did not
      differ (p > 0.5). CONCLUSION: The porcine bile duct exhibited nonlinear
      anisotropic mechanical properties.

PMID- 15260882
TI  - Randomized comparison of the effects of the vitamin D3 adequate intake versus 100
      mcg (4000 IU) per day on biochemical responses and the wellbeing of patients.
AB  - BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic
      and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but
      there has been no report focusing on use of this dose. METHODS: We compared
      effects of these doses on biochemical responses and sense of wellbeing in a
      blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001
      25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001.
      Biochemical responses were followed at subsequent visits that were part of
      clinical care; 37 patients completed a wellbeing questionnaire in December 2001
      and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51
      nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a
      wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In
      Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 +/- 9 (SD)
      nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79
      +/- 30 nmol/L for the 15 mcg/day group, and 112 +/- 41 nmol/L for the 100 mcg/day
      group. Both doses lowered plasma parathyroid hormone with no effect on plasma
      calcium. Between December and February, wellbeing score improved more for the 100
      mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In
      Study 2, 25(OH)D averaged 39 +/- 9 nmol/L, and winter wellbeing scores improved
      with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for
      vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was
      associated with improved wellbeing. The 100 mcg/day dose produced greater
      responses. Since it was ethically necessary to provide a meaningful dose of
      vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing
      response, particularly for those on the lower dose. This work confirms the safety
      and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed
      additional vitamin D.

PMID- 15260883
TI  - A pediatric digital storytelling system for third year medical students: the
      virtual pediatric patients.
AB  - BACKGROUND: Computer-based patient simulations (CBPS) are common, effective,
      instructional methods for medical students, but have limitations. The goal of
      this project was to describe the development of a CBPS designed to overcome some
      of these limitations and to perform an online evaluation. METHODS: In 1996,
      patients and families experiencing a common pediatric problem were interviewed,
      photographed and a chart review completed. A digital storytelling template was
      developed: 1. patient's story, evaluation and clinical course, 2. problem-based
      approach to the evaluation, and 3. discussion of disease process. The media was
      digitized and placed onto the Internet. The digital stories and a 10-question
      online survey were pilot tested. Online survey responses were collected from 1999
      2003. Overall use of the digital stories was measured by computer server logs and
      by the number of hyperlinks to the CBPS. RESULTS: Eight stories were created
      using this system. Over 4.5 years, 814,148 digital story pages were read by
      362,351 users. Hyperlink citations from other websites to the CBPS were 108.
      Online survey respondents (N = 393) described the overall quality as excellent or
      very good (88.4%). The stores were clearly written (92%) at an appropriate level
      (91.4%). Respondents felt they could begin to evaluate a similar case
      presentation (95.4%), and would remember the case in the future (91%).
      CONCLUSIONS: A new type of CBPS, the digital storytelling system, has been
      developed and evaluated which and appears to be successful in overcoming some of
      the limitations of earlier CBPS by featuring patient's stories in their own
      words, by focusing on problems rather than diseases, and by having stories that
      are quick for students to work through.

PMID- 15260884
TI  - Complementary and alternative medical therapies for chronic low back pain: What
      treatments are patients willing to try?
AB  - BACKGROUND: Although back pain is the most common reason patients use
      complementary and alternative medical (CAM) therapies, little is known about the
      willingness of primary care back pain patients to try these therapies. As part of
      an effort to refine recruitment strategies for clinical trials, we sought to
      determine if back pain patients are willing to try acupuncture, chiropractic,
      massage, meditation, and t'ai chi and to learn about their knowledge of,
      experience with, and perceptions about each of these therapies. METHODS: We
      identified English-speaking patients with diagnoses consistent with chronic low
      back pain using automated visit data from one health care organization in Boston
      and another in Seattle. We were able to confirm the eligibility status (i.e.,
      current low back pain that had lasted at least 3 months) of 70% of the patients
      with such diagnoses and all eligible respondents were interviewed. RESULTS:
      Except for chiropractic, knowledge about these therapies was low. Chiropractic
      and massage had been used by the largest fractions of respondents (54% and 38%,
      respectively), mostly for back pain (45% and 24%, respectively). Among prior
      users of specific CAM therapies for back pain, massage was rated most helpful.
      Users of chiropractic reported treatment-related "significant discomfort, pain or
      harm" more often (23%) than users of other therapies (5-16%). Respondents
      expected massage would be most helpful (median of 7 on a 0 to 10 scale) and
      meditation least helpful (median of 3) in relieving their current pain. Most
      respondents indicated they would be "very likely" to try acupuncture, massage, or
      chiropractic for their back pain if they did not have to pay out of pocket and
      their physician thought it was a reasonable treatment option. CONCLUSIONS: Most
      patients with chronic back pain in our sample were interested in trying
      therapeutic options that lie outside the conventional medical spectrum. This
      highlights the need for additional studies evaluating their effectiveness and
      suggests that researchers conducting clinical trials of these therapies may not
      have difficulties recruiting patients.

PMID- 15260885
TI  - Effectiveness of vasectomy using cautery.
AB  - BACKGROUND: Little evidence supports the use of any one vas occlusion method.
      Data from a number of studies now suggest that there are differences in
      effectiveness among different occlusion methods. The main objectives of this
      study were to estimate the effectiveness of vasectomy by cautery and to describe
      the trends in sperm counts after cautery vasectomy. Other objectives were to
      estimate time and number of ejaculations to success and to determine the
      predictive value of success at 12 weeks for final status at 24 weeks. METHODS: A
      prospective, non-comparative observational study was conducted between November
      2001 and June 2002 at 4 centers in Brazil, Canada, the UK, and the US. Four
      hundred men who chose vasectomy were enrolled and followed for 6 months. Sites
      used their usual cautery vasectomy technique. Earlier and more frequent than
      normal semen analyses (2, 5, 8, 12, 16, 20, and 24 weeks after vasectomy) were
      performed. Planned outcomes included effectiveness (early failure based on semen
      analysis), trends in sperm counts, time and number of ejaculations to success,
      predictive value of success at 12 weeks for the outcome at 24 weeks, and safety
      evaluation. RESULTS: A total of 364 (91%) participants completed follow-up. The
      overall failure rate based on semen analysis was 0.8% (95% confidence interval
      0.2, 2.3). By 12 weeks 96.4% of participants showed azoospermia or severe
      oligozoospermia (< 100,000 sperm/mL). The predictive value of a single severely
      oligozoospermia sample at 12 weeks for vasectomy success at the end of the study
      was 99.7%. One serious unrelated adverse event and no pregnancies were reported.
      CONCLUSION: Cautery is a very effective method for occluding the vas. Failure
      based on semen analysis is rare. In settings where semen analysis is not
      practical, using 12 weeks as a guideline for when men can rely on their vasectomy
      should lessen the risk of failure compared to using a guideline of 20
      ejaculations after vasectomy.

PMID- 15260886
TI  - Oxidative stress in term small for gestational age neonates born to
      undernourished mothers: a case control study.
AB  - BACKGROUND: The objective of this study was to assess the status of oxidative
      stress in term small for gestational age (SGA) newborn infants born to
      undernourished mothers by estimating levels of erythrocyte superoxide dismutase
      (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord
      blood and comparing them to healthy appropriate for gestational age (AGA)
      controls. This was done in a case control design at a tertiary level teaching
      hospital. METHODS: We included 20 singleton healthy SGA newborn infants born
      between 38-40 weeks to undernourished mothers with a) post-pregnancy weight < 50
      kg or height < 145 cm AND b) hemoglobin < 8.0 g/dL or serum albumin < 2.5 g/dL.
      An equal number of age and sex matched AGA newborn infants born to healthy
      mothers served as Controls. Mothers with other risk factors and newborns with
      complications during delivery or immediate newborn period were excluded. MDA,
      SOD, catalase and reduced glutathione were measured in the cord blood of all
      neonates and compared between the groups (unpaired t test); levels were also
      correlated to maternal weight, height, hemoglobin, and albumin by both univariate
      (pearsonian correlation) and multivariate (multiple regression) analysis.
      RESULTS: The activity of MDA was increased (5.33 +/- 0.72 vs 2.55 +/- 0.22
      nmol/mL; P < 0.0001) while levels of superoxide dismutase (493.6 +/- 54.9 vs.
      786.8 +/- 79.1 U/g Hb; P < 0.0001), catalase (1.48 +/- 0.24 vs. 2.31 +/- 0.20 U/g
      Hb; P < 0.0001) and reduced glutathione (2.84 +/- 0.37 vs 6.42 +/- 0.23 Umol/g
      Hb, P < 0.0001) were decreased in term SGA born to undernourished mothers as
      compared to term AGA born to healthy mothers. On univariate analysis, all the
      markers of oxidative stress correlated significantly with maternal parameters (P
      < 0.005). On multivariate analysis, maternal albumin and hemoglobin accounted for
      maximum correlation with the markers of oxidative stress. CONCLUSIONS:
      Intrauterine malnutrition is associated with significant oxidative stress in
      small for gestational age neonates born at term to malnourished mothers.

PMID- 15260887
TI  - Assessing harmful effects in systematic reviews.
AB  - BACKGROUND: Balanced decisions about health care interventions require reliable
      evidence on harms as well as benefits. Most systematic reviews focus on efficacy
      and randomised trials, for which the methodology is well established. Methods to
      systematically review harmful effects are less well developed and there are few
      sources of guidance for researchers. We present our own recent experience of
      conducting systematic reviews of harmful effects and make suggestions for future
      practice and further research. METHODS: We described and compared the methods
      used in three systematic reviews. Our evaluation focused on the review question,
      study designs and quality assessment. RESULTS: One review question focused on
      providing information on specific harmful effects to furnish an economic model,
      the other two addressed much broader questions. All three reviews included
      randomised and observational data, although each defined the inclusion criteria
      differently. Standard methods were used to assess study quality. Various
      practical problems were encountered in applying the study design inclusion
      criteria and assessing quality, mainly because of poor study design, inadequate
      reporting and the limitations of existing tools. All three reviews generated a
      large volume of work that did not yield much useful information for health care
      decision makers. The key areas for improvement we identified were focusing the
      review question and developing methods for quality assessment of studies of
      harmful effects. CONCLUSIONS: Systematic reviews of harmful effects are more
      likely to yield information pertinent to clinical decision-making if they address
      a focused question. This will enable clear decisions to be made about the type of
      research to include in the review. The methodology for assessing the quality of
      harmful effects data in systematic reviews requires further development.

PMID- 15260888
TI  - Characterization of HPV16 L1 loop domains in the formation of a type-specific,
      conformational epitope.
AB  - BACKGROUND: Virus-like particles (VLPs) formed by the human papillomavirus (HPV)
      L1 capsid protein are currently being tested in clinical trials as prophylactic
      vaccines against genital warts and cervical cancer. The efficacy of these
      vaccines is critically dependent upon L1 type-specific conformational epitopes.
      To investigate the molecular determinants of the HPV16 L1 conformational epitope
      recognized by monoclonal antibody 16A, we utilized a domain-swapping approach to
      generate a series of L1 proteins composed of a canine oral papillomavirus (COPV)
      L1 backbone containing different regions of HPV16 L1. RESULTS: Gross domain
      swaps, which did not alter the ability of L1 to assemble into VLPs, demonstrated
      that the L1 N-terminus encodes at least a component of the 16A antigenic
      determinant. Finer epitope mapping, using GST-L1 fusion proteins, mapped the 16A
      epitope to the L1 variable regions I and possibly II within the N-terminus.
      CONCLUSIONS: These results suggest that non-contiguous loop regions of L1 display
      critical components of a type-specific, conformational epitope.

PMID- 15260889
TI  - A molecular 'signature' of primary breast cancer cultures; patterns resembling
      tumor tissue.
AB  - BACKGROUND: To identify the spectrum of malignant attributes maintained outside
      the host environment, we have compared global gene expression in primary breast
      tumors and matched short-term epithelial cultures. RESULTS: In contrast to
      immortal cell lines, a characteristic 'limited proliferation' phenotype was
      observed, which included over expressed genes associated with the TGFbeta signal
      transduction pathway, such as SPARC, LOXL1, RUNX1, and DAPK1. Underlying this
      profile was the conspicuous absence of hTERT expression and telomerase activity,
      a significant increase in TbetaRII, its cognate ligand, and the CDK inhibitor,
      p21CIP1/WAF1. Concurrently, tumor tissue and primary cultures displayed low
      transcript levels of proliferation-related genes, such as, TOP2A, ANKT, RAD51,
      UBE2C, CENPA, RRM2, and PLK. CONCLUSIONS: Our data demonstrate that commonly used
      immortal cell lines do not reflect some aspects of tumor biology as closely as
      primary tumor cell cultures. The gene expression profile of malignant tissue,
      which is uniquely retained by cells cultured on solid substrates, could
      facilitate the development and testing of novel molecular targets for breast
      cancer.

PMID- 15260890
TI  - The molecular basis of electroporation.
AB  - BACKGROUND: Electroporation is a common method to introduce foreign molecules
      into cells, but its molecular basis is poorly understood. Here I investigate the
      mechanism of pore formation by direct molecular dynamics simulations of
      phospholipid bilayers of a size of 256 and of more than 2000 lipids as well as
      simulations of simpler interface systems with applied electric fields of
      different strengths. RESULTS: In a bilayer of 26 x 29 nm multiple pores form
      independently with sizes of up to 10 nm on a time scale of nanoseconds with an
      applied field of 0.5 V/nm. Pore formation is accompanied by curving of the
      bilayer. In smaller bilayers of ca. 6 x 6 nm, a single pore forms on a nanosecond
      time scale in lipid bilayers with applied fields of at least 0.4 V/nm,
      corresponding to transmembrane voltages of ca. 3 V. The presence of 1 M salt does
      not seem to change the mechanism. In an even simpler system, consisting of a 3 nm
      thick octane layer, pores also form, despite the fact that there are no charged
      headgroups and no salt in this system. In all cases pore formation begins with
      the formation of single-file like water defects penetrating into the bilayer or
      octane. CONCLUSIONS: The simulations suggest that pore formation is driven by
      local electric field gradients at the water/lipid interface. Water molecules move
      in these field gradients, which increases the probability of water defects
      penetrating into the bilayer interior. Such water defects cause a further
      increase in the local electric field, accelerating the process of pore formation.
      The likelihood of pore formation appears to be increased by local membrane
      defects involving lipid headgroups. Simulations with and without salt show little
      difference in the observed pore formation process. The resulting pores are
      hydrophilic, lined by phospholipid headgroups.

PMID- 15260891
TI  - Editorial: The informatics of post-translational modification and its
      implications for systems biology.

PMID- 15260892
TI  - From masking repeats to identifying functional repeats in the mouse
      transcriptome.
AB  - The back-to-back release of the mouse genome and the functionally annotated RIKEN
      mouse full-length cDNA collection was an important milestone in mammalian
      genomics. Yet much of the data remain to be explored in terms of biological
      effects and mechanisms. For example, interspersed repeats account for 39 per cent
      of the mouse genome sequence and 11 per cent of representative transcripts. A
      considerable number of transposable repeat elements are still active and
      propagating in mouse compared with human. While existing repeat databases and
      tools assist the classification of repeats or identification of new repeats,
      there is little bioinformatic support towards exploring the extent and role of
      repeats in transcriptional variation, modulation of protein function, or gene
      regulatory events. Since the mouse is used as a model organism to study human
      genes and their disease associations, this review focuses on information
      extraction and collation that captures the functional context of repeats in mouse
      transcripts to facilitate the biological interpretation and extrapolation of
      findings to the human.

PMID- 15260893
TI  - Probabilistic methods of identifying genes in prokaryotic genomes: connections to
      the HMM theory.
AB  - In this paper, we review developments in probabilistic methods of gene
      recognition in prokaryotic genomes with the emphasis on connections to the
      general theory of hidden Markov models (HMM). We show that the Bayesian method
      implemented in GeneMark, a frequently used gene-finding tool, can be augmented
      and reintroduced as a rigorous forward-backward (FB) algorithm for local
      posterior decoding described in the HMM theory. Another earlier developed method,
      prokaryotic GeneMark.hmm, uses a modification of the Viterbi algorithm for HMM
      with duration to identify the most likely global path through hidden functional
      states given the DNA sequence. GeneMark and GeneMark.hmm programs are worth using
      in concert for analysing prokaryotic DNA sequences that arguably do not follow
      any exact mathematical model. The new extension of GeneMark using the FB
      algorithm was implemented in the software program GeneMark.fba. Given the DNA
      sequence, this program determines an a posteriori probability for each nucleotide
      to belong to coding or non-coding region. Also, for any open reading frame (ORF),
      it assigns a score defined as a probabilistic measure of all paths through hidden
      states that traverse the ORF as a coding region. The prediction accuracy of
      GeneMark.fba determined in our tests was compared favourably to the accuracy of
      the initial (standard) GeneMark program. Comparison to the prokaryotic
      GeneMark.hmm has also demonstrated a certain, yet species-specific, degree of
      improvement in raw gene detection, ie detection of correct reading frame (and
      stop codon). The accuracy of exact gene prediction, which is concerned about
      precise prediction of gene start (which in a prokaryotic genome unambiguously
      defines the reading frame and stop codon, thus, the whole protein product), still
      remains more accurate in GeneMarkS, which uses more elaborate HMM to specifically
      address this task.

PMID- 15260894
TI  - Computational approaches for the analysis of gene neighbourhoods in prokaryotic
      genomes.
AB  - Gene order in prokaryotes is conserved to a much lesser extent than protein
      sequences. Only some operons, primarily those that encode physically interacting
      proteins, are conserved in all or most of the bacterial and archaeal genomes.
      Nevertheless, even the limited conservation of operon organisation that is
      observed provides valuable evolutionary and functional clues through multiple
      genome comparisons. With the rapid growth in the number and diversity of
      sequenced prokaryotic genomes, functional inferences for uncharacterized genes
      located in the same conserved gene neighborhood with well-studied genes are
      becoming increasingly important. In this review, we discuss various computational
      approaches for identification of conserved gene strings and construction of local
      alignments of gene orders in prokaryotic genomes.

PMID- 15260895
TI  - MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and
      sequence alignment.
AB  - With its theoretical basis firmly established in molecular evolutionary and
      population genetics, the comparative DNA and protein sequence analysis plays a
      central role in reconstructing the evolutionary histories of species and
      multigene families, estimating rates of molecular evolution, and inferring the
      nature and extent of selective forces shaping the evolution of genes and genomes.
      The scope of these investigations has now expanded greatly owing to the
      development of high-throughput sequencing techniques and novel statistical and
      computational methods. These methods require easy-to-use computer programs. One
      such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA)
      software, with its focus on facilitating the exploration and analysis of the DNA
      and protein sequence variation from an evolutionary perspective. Currently in its
      third major release, MEGA3 contains facilities for automatic and manual sequence
      alignment, web-based mining of databases, inference of the phylogenetic trees,
      estimation of evolutionary distances and testing evolutionary hypotheses. This
      paper provides an overview of the statistical methods, computational tools, and
      visual exploration modules for data input and the results obtainable in MEGA.

PMID- 15260896
TI  - Bioinformatics for glycomics: status, methods, requirements and perspectives.
AB  - The term 'glycomics' describes the scientific attempt to identify and study all
      the glycan molecules - the glycome - synthesised by an organism. The aim is to
      create a cell-by-cell catalogue of glycosyltransferase expression and detected
      glycan structures. The current status of databases and bioinformatics tools,
      which are still in their infancy, is reviewed. The structures of glycans as
      secondary gene products cannot be easily predicted from the DNA sequence. Glycan
      sequences cannot be described by a simple linear one-letter code as each pair of
      monosaccharides can be linked in several ways and branched structures can be
      formed. Few of the bioinformatics algorithms developed for genomics/proteomics
      can be directly adapted for glycomics. The development of algorithms, which allow
      a rapid, automatic interpretation of mass spectra to identify glycan structures
      is currently the most active field of research. The lack of generally accepted
      ways to normalise glycan structures and exchange glycan formats hampers an
      efficient cross-linking and the automatic exchange of distributed data. The
      upcoming glycomics should accept that unrestricted dissemination of scientific
      data accelerates scientific findings and initiates a number of new initiatives to
      explore the data.

PMID- 15260897
TI  - Delineation of modular proteins: domain boundary prediction from sequence
      information.
AB  - The delineation of domain boundaries of a given sequence in the absence of known
      3D structures or detectable sequence homology to known domains benefits many
      areas in protein science, such as protein engineering, protein 3D structure
      determination and protein structure prediction. With the exponential growth of
      newly determined sequences, our ability to predict domain boundaries rapidly and
      accurately from sequence information alone is both essential and critical from
      the viewpoint of gene function annotation. Anyone attempting to predict domain
      boundaries for a single protein sequence is invariably confronted with a plethora
      of databases that contain boundary information available from the internet and a
      variety of methods for domain boundary prediction. How are these derived and how
      well do they work? What definition of 'domain' do they use? We will first clarify
      the different definitions of protein domains, and then describe the available
      public databases with domain boundary information. Finally, we will review
      existing domain boundary prediction methods and discuss their strengths and
      weaknesses.

PMID- 15260898
TI  - Jemboss reloaded.
AB  - Bioinformatics tools are freely available from websites all over the world. Often
      they are presented as web services, although there are many tools for download
      and use on a local machine. This tutorial section looks at Jemboss, a Java-based
      graphical user interface (GUI) for the EMBOSS bioinformatics suite, which
      combines the advantages of both web service and downloaded software.

PMID- 15260900
TI  - A placebo-controlled study of lofexidine in the treatment of children with tic
      disorders and attention deficit hyperactivity disorder.

PMID- 15260902
TI  - Effects of the atypical antipsychotic olanzapine on reproductive function and
      weight gain in female rats.
AB  - Sexual dysfunction is a major, although poorly understood, side-effect of
      treatment with antipsychotic drugs. We have recently show marked disruption of
      reproductive function and weight gain in female rats treated subchronically with
      risperidone and haloperidol. The aim of the present study was to examine further
      the potential relationship between reproductive dysfunction and weight gain in
      female rats treated with olanzapine. The effects of olanzapine on weight gain,
      food and water intake, intra-abdominal fat, the oestrous cycle and uterine weight
      were assessed in group-housed adult female hooded-Lister rats. Olanzapine (0.5
      4.0 mg/kg i.p.) or vehicle was administered once daily for 21 days and body
      weight, food and water intake measured, with histological examination of vaginal
      lavage to determine the stage of the oestrous cycle. On day 22, animals were
      sacrificed and intra-abdominal fat, wet and dry uterine weights measured.
      Olanzapine induced significant weight gain with concomitant increases in food and
      water intake and intra-abdominal fat without an effect on the oestrous cycle, wet
      and dry uterine weights or plasma prolactin levels. These results confirm the
      ability of olanzapine to induce weight gain in female rats on unrestricted normal
      diet with a concomitant increase in food and water intake and increased intra
      abdominal fat. These effects of olanzapine were produced in the absence of any
      apparent impairment in reproductive function, in contrast to the substantial
      disruption of oestrous and uterine atrophy previously shown in rats treated with
      risperidone and haloperidol.

PMID- 15260903
TI  - Effects of amisulpride, risperidone and chlorpromazine on auditory and visual
      latent inhibition, prepulse inhibition, executive function and eye movements in
      healthy volunteers.
AB  - In view of the evidence that cognitive deficits in schizophrenia are critically
      important for long-term outcome, it is essential to establish the effects that
      the various antipsychotic compounds have on cognition, particularly second
      generation drugs. This parallel group, placebo-controlled study aimed to compare
      the effects in healthy volunteers (n = 128) of acute doses of the atypical
      antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of
      chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process:
      auditory and visual latent inhibition, prepulse inhibition of the acoustic
      startle response, executive function and eye movements. The drugs tested were not
      found to affect auditory latent inhibition, prepulse inhibition or executive
      functioning as measured by the Cambridge Neuropsychological Test Battery and the
      FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed
      a trend to disrupt visual latent inhibition. Although amisulpride did not affect
      eye movements, both risperidone and chlorpromazine decreased peak saccadic
      velocity and increased antisaccade error rates, which, in the risperidone group,
      correlated with drug-induced akathisia. It was concluded that single doses of
      these drugs appear to have little effect on cognition, but may affect eye
      movement parameters in accordance with the amount of sedation and akathisia they
      produce. The effect risperidone had on latent inhibition is likely to relate to
      its serotonergic properties. Furthermore, as the trend for disrupted visual
      latent inhibition following amisulpride was similar in nature to that which would
      be expected with amphetamine, it was concluded that its behaviour in this model
      is consistent with its preferential presynaptic dopamine antagonistic activity in
      low dose and its efficacy in the negative symptoms of schizophrenia.

PMID- 15260904
TI  - Effects of quetiapine and haloperidol on prepulse inhibition of the acoustic
      startle (eyeblink) response and the N1/P2 auditory evoked response in man.
AB  - Contraction of the orbicularis oculi muscle in response to a sudden loud sound
      (acoustic startle response) and the N1/P2 component of the auditory evoked
      potential are both attenuated when a brief low-intensity stimulus is presented 30
      500 ms before the 'startle-eliciting' stimulus (PPI). Here, we report the effects
      of the 'atypical' antipsychotic drug quetiapine and the 'conventional'
      antipsychotic haloperidol on these responses. Sixteen males (aged 19-38 years)
      participated in four sessions at 7-day intervals, in which they received
      quetiapine 12.5 mg, quetiapine 25 mg, haloperidol 3 mg and placebo, according to
      a balanced double-blind design. Electromyographic (EMG) responses of the
      orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a
      20-min session, 2 h after treatment. Subjects received 40 trials in which 1-kHz
      sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms,
      85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean
      amplitudes of the EMG response and the N1/P2 potential were derived from the
      pulse-alone trials and, in each case, percentage PPI was calculated. Serum
      prolactin was measured after each treatment, and autonomic (heart rate, blood
      pressure, salivation) and psychological (visual analogue self-ratings of mood and
      alertness, critical flicker fusion frequency) measures were taken before and
      after each treatment. Quetiapine 12.5 mg and 25 mg significantly reduced the
      amplitude of the EMG response without altering its inhibition by prepulses;
      haloperidol had no effect on EMG response amplitude or PPI. Neither drug affected
      N1/P2 amplitude or PPI of this response. Quetiapine, but not haloperidol, reduced
      subjective alertness and critical flicker fusion frequency. Haloperidol, but not
      quetiapine, elevated serum prolactin level. The ability of quetiapine to
      attenuate the startle response may reflect its sedative action.

PMID- 15260905
TI  - The influence of schizotypy traits on prepulse inhibition in young healthy
      controls.
AB  - Deficits in sensorimotor gating or prepulse inhibition (PPI) have been
      demonstrated repeatedly in patients with schizophrenia or with schizotypal
      personality disorder, but not consistently in schizotypal non-psychiatric
      controls. The appearance of normal PPI in this group has been interpreted as
      reflecting a discontinuous underlying vulnerability to psychosis in high-risk
      groups. An alternative interpretation is that underlying vulnerability to
      psychosis is continuously distributed in the normal population (Claridge, 1972,
      1987), and therefore that performance on information processing tasks should vary
      continuously with increasing levels of schizotypy in non-clinical populations. We
      attempted to examine further the notion of a continuous relationship between PPI
      and schizotypy in 44 (17 female, 27 male) healthy, non-smoking subjects
      controlling for menstrual phase. In this selected sample, the findings do not
      support a continuum model, and suggest that PPI deficits may indeed be the result
      of a discontinuous neurophysiological change in those with psychotic illness,
      rather than one continuously distributed in the normal population.

PMID- 15260906
TI  - QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations.
AB  - The role of certain drug metabolizing enzymes in cardiotoxicity, such as CYP2D6
      for thioridazine, has been suggested. Risperidone has been shown to inhibit the
      delayed rectifier leading to lengthening of cardiac repolarization. The heart
      rate corrected QT (QTc) interval lengthening has been reported in psychiatric
      patients receiving risperidone under steady-state conditions. CYP2D6 is involved
      in the metabolism of risperidone to 9-hydroxy (OH)-risperidone. CYP2C9 enzyme is
      also involved in the metabolism of several psychotropic drugs, although there are
      no data about its implication in risperidone metabolism. The present study aimed
      to evaluate the influence of CYP2D6 and CYP2C9 genotypes, and plasma
      concentrations of risperidone and 9-OH-risperidone on the QTc interval in
      patients under steady-state conditions. The relevance of CYP2D6 and CYP2C9
      genotypes on risperidone metabolism was also analysed. Thirty-five White European
      psychiatric patients receiving risperidone monotherapy were studied. QTc interval
      was longer (p < 0.05) in subjects with one active CYP2D6 gene compared to those
      with two. The number of CYP2D6 active genes was related to the dose-corrected
      plasma concentration of risperidone (p < 0.05), the active moiety (risperidone
      plus 9-OH-risperidone) (p < 0.05) and the risperidone/9-OH-risperidone ratio (p <
      0.05). CYP2C9 genotypes were not related to plasma concentrations of risperidone
      or 9-OH-risperidone, nor QTc interval. The results suggest that CYP2D6, but not
      CYP2C9, may be related to QTc lengthening during treatment with risperidone. The
      effect of the CYP2D6 genotype in risperidone metabolism is also shown.

PMID- 15260907
TI  - The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in
      healthy volunteers.
AB  - Previous studies suggest a modulatory role of serotonin (5-HT) in experimentally
      induced panic attacks. In the current study, we investigated the acute effects of
      5-HT precursor l-5-hydroxytryptophan (5-HTP) on the response to panicogenic
      challenge with cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. Thirty
      two subjects were randomized to receive either 200 mg of 5-HTP or placebo with
      the CCK-4 challenge following in 90 min in a double-blind, parallel-group design.
      The results showed a nonsignificant difference between the groups in panic rate
      (19% after 5-HTP and 44% after placebo, p = 0.13) with a trend for lower
      intensity of symptoms after 5-HTP (p = 0.08). Further analysis by gender revealed
      that females in the 5-HTP group had a significantly lower panic rate and
      intensity of cognitive symptoms whereas, in males, the effect of 5-HTP was
      limited to lowering the intensity of somatic panic symptoms. Thus, an increased
      availability of 5-HT may have a gender-dependent protective effect in CCK-4
      induced panic.

PMID- 15260908
TI  - Tolerability of high-dose venlafaxine in depressed patients.
AB  - High doses of antidepressants are often used for treatment-resistant depression.
      Venlafaxine, a dual serotonin and noradrenaline reuptake inhibitor, has been
      shown to have a tolerable side-effect profile in previous studies using doses of
      up to 375 mg/day. We investigated the tolerability of higher than currently
      recommended doses of venlafaxine using the UKU side-effect rating scale. Seventy
      outpatients fulfilling DSM-IV criteria for major depressive disorder were
      recruited into two demographically matched groups according to their daily dosage
      of venlafaxine: high dose n = 35 (> or = 375 mg/day, range 375-600 mg, average
      437 mg/day) or standard dose n = 35 (< 375 mg/day, range 75-300 mg, average 195
      mg/day. Clinical characteristics were noted and the UKU side-effect rating scale
      was administered to a subsample of patients. The most frequently reported
      complaints in both groups were increased fatigue (48%), concentration
      difficulties (48%), sleepiness/sedation (37%), failing memory (44.4%) and weight
      gain (29.6%). Apart from weight gain, the complaints were found to be experienced
      significantly more severely by the high-dose group. Six patients discontinued
      venlafaxine due to intolerable side-effects but only two of these patients were
      on a high dose. There was a tendency for mildly raised blood pressure in 10% of
      patients on an average dose of 342 mg/day. However, no difference between the two
      groups was found. This preliminary open study demonstrates that venlafaxine is
      tolerated at higher than British National Formulary recommended doses (i.e. up to
      600 mg daily). However, increased frequency and severity of reported side-effects
      in the high-dose group are not associated with increased rates of
      discontinuation.

PMID- 15260909
TI  - A double-blind, randomized, 26-week study comparing the cognitive and psychomotor
      effects and efficacy of 75 mg (37.5 mg b.i.d.) venlafaxine and 75 mg (25 mg mane,
      50 mg nocte) dothiepin in elderly patients with moderate major depression being
      treated in general practice.
AB  - To investigate the efficacy and cognitive and psychomotor effects of venlafaxine
      and dothiepin in elderly patients with moderate major depression. A prospective,
      randomized, double-blind, parallel-group, active comparator controlled study was
      conducted. Eighty-eight patients (aged > or = 60 years) were enrolled. Each
      patient received either venlafaxine (immediate release formulation) 37.5 mg twice
      per day or dothiepin 25 mg mane followed by 50 mg nocte for 26 weeks. Efficacy
      was assessed with the Montgomery-Asberg Depression Rating Scale and the Hamilton
      Depression Rating Scale. A psychometric test battery to assess cognitive
      function, activities of daily living and sleep consisted of Critical Flicker
      Fusion (CFF), Short-term Memory--Kim's Game, Cognitive Failures Questionnaire,
      Milford Epworth Sleepiness Scale, Leeds Sleep Evaluation Questionnaire, and an
      Accident Scoring Questionnaire. Quality of Life Questionnaires (Short Form 36 and
      Quality of Life in Depression Scale) were also administered. Venlafaxine
      significantly (p < 0.05) raised CFF scores compared to baseline but had no effect
      on any other measure. Dothiepin significantly (p < 0.05) lowered CFF threshold,
      and increased ratings of both sedation and difficulty in waking. The results
      showed that venlafaxine at doses of 37.5 mg b.i.d. in elderly depressed patients
      is free from disruptive effects on cognitive function and psychomotor
      performance.

PMID- 15260910
TI  - Noradrenergic activity is associated with response to pindolol in aggressive
      Alzheimer's disease patients.
AB  - Loss of noradrenergic (NE) neurones in the locus ceruleus and compensatory
      changes in NE activity have been described in Alzheimer's disease (AD), but have
      never been linked to treatment. The hypothesis of this study was that central NE
      responsivity would predict aggression response to treatment with a NE medication,
      pindolol. Fifteen institutionalized AD subjects [Mini-Mental State Examination
      (MMSE), mean 3.3 +/- 4.6] with significant behavioural disturbances
      (Neuropsychiatric Inventory Score, mean 30.6 +/- 14.6) were studied. Growth
      hormone (GH) response to clonidine challenge (5 microg/kg) was used as a measure
      of central NE responsivity. Subjects were then randomized to 7 weeks of treatment
      with pindolol, maximum dose 20 mg b.i.d., or an identical placebo capsule in a
      cross-over design. The primary outcome measure was change on the retrospective
      Overt Aggression Scale (r-OAS). Five of 11 completers (45%) had decreased total r
      OAS scores. There was significant improvement noted on the r-OAS verbal
      aggression subscale (paired t = -2.5, p = 0.03) compared to placebo, but not r
      OAS total. Higher baseline aggression, higher MMSE and lower GH response
      predicted improvement in aggression, accounting for 82% of the variance (r =
      0.91, F = 10.5, p = 0.006). Changes in NE responsivity, as reflected by a blunted
      GH response to clonidine challenge and more severe aggression, were associated
      with better response to the NE agent pindolol. Individual patient
      characteristics, including underlying neurotransmitter changes, may be useful for
      predicting response to therapy.

PMID- 15260911
TI  - Pharmacokinetic/pharmacodynamic assessment of tolerance to central nervous system
      effects of a 3 mg sustained release tablet of rilmenidine in hypertensive
      patients.
AB  - Previous single-dose studies have shown clear blood pressure-lowering effects of
      a potential sustained release (SR) profile of rilmenidine, with concentration
      dependent effects on the central nervous system. The aim of this study was to
      evaluate potential changes in concentration-effect-relationships for these
      central nervous system effects during a 4-week treatment period with an
      experimental SR formulation of rilmenidine 3 mg once daily in 15 mild-to-moderate
      hypertensive patients. The central nervous system effects of the treatment were
      evaluated using saccadic eye movements for sedative effects and visual analogue
      scales for subjective effects on alertness, mood and calmness. Measurements for
      pharmacokinetic and pharmacodynamic evaluations were performed on the first day
      of the treatment period and repeated after 1 week and 4 weeks of treatment. Drug
      concentrations increased during the study, whereas treatment related reductions
      in saccadic peak velocity (SPV) remained similar on all three study days. The
      slopes of the concentration-effect-curves for SPV remained unchanged throughout
      the study, while the intercepts tended to increase as a result of increased pre
      dose values. Similar effects were observed for visual analogue scales for
      alertness: pre-dose values increased significantly during the study, while the
      size of the treatment responses (slopes) remained unaltered. The reasons for
      these adaptations cannot be determined but may include drug tolerance and
      habituations to study procedures. Blood pressure control remained stable and
      adequate throughout the study.

PMID- 15260912
TI  - Recreational drug use: patterns from a South Wales self-report survey.
AB  - This study aimed to examine patterns of illicit recreational drug use, alcohol
      consumption, and smoking in a community-based population sample. A postal
      questionnaire survey was conducted of people who were selected at random from the
      Electoral registers of Cardiff and Merthyr Tydfil. Twelve percent of respondents
      reported illicit recreational drug use in the last year, and 7% in the last
      month. Among respondents aged under 25 years, 34% (39% of males and 31% of
      females) had used illicit drugs in the last year, and 19% (23% of males and 17%
      of females) in the last month. Twenty-one percent of respondents smoked (20% of
      males and 22% of females). Twenty-seven percent of respondents reported drinking
      more alcohol than currently recommended sensible limits (36% of males and 21% of
      females). Among respondents aged under 25 years, 53% of men and 38% of women
      drank over these limits. Illicit drug use was associated with heavy alcohol
      consumption and, in particular, with smoking. Smoking and heavy alcohol
      consumption combined was most strongly associated with illicit drug use. Rates of
      illicit recreational drug use were higher than have previously been reported for
      Wales. Illicit drug use and smoking varied with age, sex, work status and
      geographical location, whereas heavy alcohol consumption varied with age, sex and
      work status, but not geographical location. Both smoking and alcohol consumption
      were associated with illicit drug use, with smokers who were also heavy drinkers
      being those most likely to report illicit drug use.

PMID- 15260913
TI  - Factors associated with recreational drug use.
AB  - This study aimed to examine demographic, lifestyle, mental health and personality
      factors associated with illicit recreational drug use, heavy alcohol consumption
      and smoking in a community-based population sample. A postal questionnaire survey
      was conducted of people who were selected at random from the Electoral registers
      of Cardiff and Merthyr Tydfil. Illicit drug use was associated with risk taking,
      neuroticism, being male, having a higher education qualification, not being
      married, being unemployed, being aged under 25 years, smoking, heavy alcohol
      consumption and living in Cardiff. Smoking was associated with anxiety,
      depression, being female, lower income and educational qualifications, looking
      after the family or home, being aged over 25 years, illicit drug use and heavy
      alcohol use. Heavy alcohol consumption was associated with not being depressed,
      experiencing sleeping problems, risk taking, being male, higher income, no higher
      educational qualification, not being married, being a student, being aged under
      25 years, smoking and illicit drug use. Illicit drug use, smoking and heavy
      alcohol use were strongly associated with each other. Illicit drug use was
      associated with alcohol use and, to an even greater extent, with smoking. Illicit
      drug and alcohol use were associated with similar characteristics, but smoking
      was associated with a rather different demographic combination.

PMID- 15260914
TI  - Introduction to systematic reviews.

PMID- 15260915
TI  - Folate for depressive disorders: systematic review and meta-analysis of
      randomized controlled trials.
AB  - The objective of this review was to determine the effectiveness, adverse effects
      and acceptability of folate in the treatment of depression. Electronic databases
      (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression,
      Anxiety and Neurosis Controlled Trials Register) and reference lists were
      searched, and authors, experts and pharmaceutical companies contacted to identify
      randomized controlled trials that compared treatment with folic acid or 5'
      methyltetrahydrofolic acid to an alternative treatment, for patients with a
      diagnosis of depressive disorder. Three randomized trials (247 participants) were
      included. Two studies assessed the use of folate in addition to other treatment,
      and found that adding folate reduced Hamilton Depression Rating Scale (HDRS)
      scores on average by a further 2.65 points [95% confidence interval (CI) 0.38
      4.93]. Fewer patients treated with folate experienced a reduction in their HDRS
      score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The
      remaining study found no statistically significant difference when folate alone
      was compared with trazodone. The identified trials did not find evidence of any
      problems with the acceptability or safety of folate. The limited available
      evidence suggests folate may have a potential role as a supplement to other
      treatment for depression. It is currently unclear if this is the case both for
      people with normal folate levels, and for those with folate deficiency.

PMID- 15260916
TI  - Transcranial magnetic stimulation: applications for neuropsychopharmacology.
AB  - Transcranial magnetic stimulation (TMS) provides new possibilities for studying
      localized changes in the electrical properties of the human cortex. TMS combined
      with electromyography (EMG) has revealed that drugs blocking Na(+) or Ca(2+)
      channels such as phenytoin, lamotrigin or carbamazepine change the motor
      threshold without affecting intracortical inhibition or facilitation. Gabaergic
      agents vigabatrin, lorazepam, diazepam, baclofen and ethanol do not affect the
      motor threshold, but increase intracortical inhibition and decrease facilitation.
      N-methyl-D-aspartate receptor antagonists riluzole, dextromethorphan and
      memantine have similar effects. Dopamine receptor antagonists such as
      haloperidol, but not sulpiride, decrease intracortical inhibition and increase
      intracortical facilitation. Other monoamines, such as serotonin and
      noradrenaline, may have some modulating effect on the cortical excitability.
      However, TMS combined with EMG gives only indirect evidence about the
      excitability of the motor cortex because spinal mechanisms may contribute to the
      results. Cortical excitability can be studied directly by combining TMS with
      brain imaging methods such as electroencephalography (EEG). Motor and non-motor
      areas can be stimulated and subsequent brain activity can be measured. Ethanol
      has been shown to modulate EEG responses evoked by motor-cortex TMS, the effects
      being largest at the right prefrontal cortex, meaning that ethanol would have
      changed the functional connectivity. Furthermore, alcohol decreases amplitudes of
      EEG responses after the left prefrontal stimulation mainly in anterior parts of
      the cortex, which may be associated with the decrease of the prefrontal cortical
      excitability. Taken together, TMS provides a new insight to the actions of
      central nervous system drugs at the cortical level.

PMID- 15260917
TI  - Pharmacokinetic interactions of drugs with St John's wort.
AB  - There is a worldwide increasing use of herbs which are often administered in
      combination with therapeutic drugs, raising the potential for herb-drug
      interactions. St John's wort (Hypericum perforatum) is one of the most commonly
      used herbal antidepressants. A literature search was performed using Medline (via
      Pubmed), Biological Abstracts, Cochrane Library, AMED, PsycINFO and Embase (all
      from their inception to September 2003) to identify known drug interaction with
      St John's wort. The available data indicate that St John's wort is a potent
      inducer of CYP 3A4 and P-glycoprotein (PgP), although it may inhibit or induce
      other CYPs, depending on the dose, route and duration of administration. Data
      from human studies and case reports indicate that St John's wort decreased the
      blood concentrations of amitriptyline, cyclosporine, digoxin, fexofenadine,
      indinavir, methadone, midazolam, nevirapine, phenprocoumon, simvastatin,
      tacrolimus, theophylline and warfarin, whereas it did not alter the
      pharmacokinetics of carbamazepine, dextromethorphan, mycophenolic acid and
      pravastatin. St John's wort decreased the plasma concentration of the active
      metabolite SN-38 in cancer patients receiving irinotecan treatment. St John's
      wort did not alter the pharmacokinetics of tolbutamide, but increased the
      incidence of hypoglycaemia. Several cases have been reported that St John's wort
      decreased cyclosporine blood concentration leading to organ rejection. St John's
      wort caused breakthrough bleeding and unplanned pregnancies when used
      concomitantly with oral contraceptives. It also caused serotonin syndrome when
      coadministered with selective serotonin-reuptake inhibitors (e.g. sertaline and
      paroxetine). Both pharmacokinetic and pharmacodynamic components may play a role
      in these interactions. Because the potential interaction of St John's wort with
      other drugs is a major safety concern, additional systematic research on herb
      drug interactions and appropriate regulation in herbal safety and efficacy is
      needed.

PMID- 15260918
TI  - Oral transmucosal abuse of transdermal fentanyl.
AB  - Transdermal fentanyl is an opioid analgesic that is effective on chronic pain,
      and which appears to be advantageous due to several factors such as ease of
      administration, the relatively stable serum concentration and long dose
      intervals. Nevertheless, the danger of abuse and dependence exists among patients
      who are prescribed fentanyl patches. We present a case of transdermal fentanyl
      abuse, where the administration route of the drug was changed. Our patient, who
      had no history of substance abuse and who suffered from chronic nonmalignant
      pain, used the fentanyl transdermal patches as oral transmucosal medication,
      raising the dose by ten-fold. This abuse of the drug was only for analgesic
      purposes without seeking anxiolysis and/or euphoria. After treatment and
      progressive reduction of fentanyl, the patient remains in good condition, and is
      currently taking the initial dose of the drug transdermally, without having
      experienced any withdrawal symptoms.

PMID- 15260919
TI  - Does quetiapine have mood altering properties?
AB  - We present a series of three cases who developed manic symptoms on introduction
      of quetiapine to their medication regime. All were male, with long-standing
      psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well
      maintained on medication until their deterioration which prompted a review of
      their medication. The dose range of prescribed quetiapine was 300-800 mg daily.
      Two patients had previously received antidepressants without displaying manic
      symptoms. The mania subsided on withdrawal of quetiapine in two patients. The
      third patient continued on quetiapine but with the addition of zuclopenthixol
      depot. Sodium valproate was prescribed to the other two patients, and quetiapine
      was discontinued. These cases indicate that a side-effect of quetiapine may be
      mood elevation. An ability to elevate mood while controlling psychoses would be
      helpful in the treatment of post-psychotic and bipolar depression. Its clinical
      importance in the control of manic episodes, for which atypical antipsychotics
      are used increasingly, is uncertain.

PMID- 15260920
TI  - Death, dependence and deception.

PMID- 15260922
TI  - When to consider urethrolysis after sling surgery.

PMID- 15260923
TI  - The medical therapy of prostatic symptoms trial.

PMID- 15260924
TI  - The relationship between erectile dysfunction and lower urinary tract symptoms:
      epidemiological, clinical, and basic science evidence.
AB  - Lower urinary tract symptoms (LUTS) and sexual dysfunction are highly prevalent
      in aging men. Both conditions also are significant contributors to overall
      quality of life. New data have emerged to indicate potential links in
      epidemiological, physiologic, pathophysiologic, and treatment aspects of these
      two entities. There are numerous publications based on sophisticated community
      and clinical-based data, suggesting a strong and consistent association between
      LUTS and erectile dysfunction (ED). The association is supported by the
      consistent linear relationship of more severe LUTS with more severe ED. The link
      between ED and LUTS has biologic plausibility given the four leading theories of
      how these diseases inter-relate.

PMID- 15260925
TI  - Mechanistic insights into the role of alpha1adrenergic receptors in lower urinary
      tract symptoms.
AB  - Although alpha(1)AR antagonists have been used for more than two decades to treat
      lower urinary tract symptoms (LUTS), we have little understanding of the
      mechanistic basis of their efficacy and their role in the development of LUTS. It
      is clear that alpha(1)ARs play a critical role in bladder dysfunction and recent
      data suggest that alpha(1)AR subtype switching may play a key role in this
      pathophysiology, providing support for use of alpha(1)(d)AR-selective antagonists
      in treating irritative symptoms. This review seeks to summarize current levels of
      understanding in this field and discusses new concepts that suggest increased
      levels of complexity involving cross-talk in multiple receptor systems. Effective
      therapeutic modalities likely will involve increased subtype selective alpha(1)AR
      antagonists and other pharmacodynamic factors.

PMID- 15260926
TI  - The use of baseline clinical measures to predict those at risk for progression of
      benign prostatic hyperplasia.
AB  - Although histologic changes of benign prostatic hyperplasia (BPH) begin in men
      when they are in their thirties, symptomatic BPH characterized by lower urinary
      tract symptoms (LUTS) typically do not develop for several decades. Progression
      of BPH may lead to significant voiding symptoms, acute urinary retention, and the
      need for prostate surgery. However, developing LUTS is not inevitable for men
      with histologic evidence of BPH. The ability to predict those men who are at risk
      for BPH progression is increasingly important because of recent evidence provided
      by the Medical Therapy of Prostate Symptoms study. This landmark study
      demonstrated that 5alpha-reductase inhibitors, alone or in combination with
      selective alpha-blockers, can delay or prevent the progression of BPH. In
      addition, the most important and consistent predictive factors for BPH
      progression are baseline prostate-specific antigen and prostate volume.
      Integration of these clinical parameters into clinical practice is influencing
      the decision regarding which men should observe or initiate treatment. This
      article highlights recent studies regarding the use of baseline clinical
      parameters on predicting BPH progression.

PMID- 15260927
TI  - The role of 5-alpha-reductase inhibition as monotherapy in view of the MTOPS
      data.
AB  - Medical treatment for the symptoms of benign prostatic hyperplasia (BPH) consists
      of a blockers and 5-alpha-reductase inhibitors. Data suggest that 5-alpha
      reductase inhibitors can prevent progression of BPH and reduce the risk of BPH
      related surgery, especially in men with large-volume prostates. Results from the
      largest randomized, prospective, placebo-controlled trial, the Medical Therapy of
      Prostatic Symptoms trial, have been presented. These results support the notion
      of using 5-alpha-reductase inhibitors for the prevention of BPH progression and
      BPH-related surgery. Furthermore, long-term 5-alpha-reductase inhibitor
      monotherapy, although slow in onset, is a viable therapy for symptom relief in
      men with mild to moderate symptoms.

PMID- 15260928
TI  - Ejaculatory disorders and lower urinary tract symptoms.
AB  - A growing body of literature supports the observed association between lower
      urinary tract symptoms and sexual dysfunction. The causal relationship between
      these two conditions has not been determined. Ejaculatory function is an
      important aspect of sexual functioning and recent studies have shown a high
      prevalence of this ejaculatory dysfunction in men with lower urinary tract
      symptoms. Furthermore, the degree of bother associated with ejaculatory
      dysfunction is quite high, making it an important problem for patients. Thus,
      health care providers should have a heightened sense of awareness for the
      presence of ejaculatory dysfunction and appropriate patient counseling should be
      undertaken before initiation of specific treatments for lower urinary tract
      symptoms.

PMID- 15260929
TI  - Long-term treatment outcomes of CoreTherm microwave feedback thermotherapy.
AB  - The gold standard for definitive management of symptomatic benign prostatic
      hypertrophy is transurethral resection of the prostate (TURP). Despite its
      efficacy, TURP has significant morbidity/mortality concerns such as hemorrhage
      and transurethral resection syndrome. This is especially worrisome for the
      medically high-risk patient, but the high rates of retrograde ejaculation found
      with TURP also pose a problem for young patients. A minimally invasive,
      outpatient alternative to TURP that has long-term efficacy, low
      morbidity/mortality, and provides a cost-effective advantage is in high demand.
      This review article discusses microwave thermotherapy as such an option and
      reports the long-term experience with the CoreTherm (CoreTherm Operations AB,
      Sweden) device.

PMID- 15260930
TI  - Epidemiology of inflammation and prostate cancer.

PMID- 15260931
TI  - The use of saw palmetto versus finasteride for the treatment of
      prostatitis/chronic pelvic pain syndrome.

PMID- 15260932
TI  - Multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome.

PMID- 15260933
TI  - Chronic pelvic pain syndrome and voiding dysfunction.
AB  - Chronic prostatitis/chronic pelvic pain syndrome is a disease that is mainly
      characterized by three parameters: pain in the suprapubic and pelvic area,
      presence or absence of white blood cells in expressed prostatic secretions, and
      voiding disorders of various degrees. The causative factors underlying this very
      common condition are poorly understood. Therapeutic options (ie, antimicrobial
      treatment) often are based on the presence of an inflammatory reaction in the
      expressed prostatic secretions, but the benefit of recurring or prolonged courses
      of antimicrobial agents is highly variable. Observations have been made regarding
      functional and structural changes in the lower urinary tract that are suggestive
      to have an impact on the pathogenesis of chronic pelvic pain syndrome.

PMID- 15260934
TI  - Acupuncture for chronic prostatitis/chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is prevalent in
      urological practice and has a significant impact on quality of life. Standard
      therapies often fail to achieve sustainable amelioration of symptoms. This
      article attempts to show that neuromodulatory treatment in the form of
      electroacupuncture can be a minimally invasive and effective treatment for
      CP/CPPS that is refractory to standard therapies. This neuromodulatory therapy
      lends support to the hypothesis that the end stage of CP/CPPS may be a
      neuropathic pain syndrome.

PMID- 15260935
TI  - Fluoroquinolone antimicrobial agents in the treatment of prostatitis and
      recurrent urinary tract infections in men.
AB  - Chronic bacterial prostatitis is the most frequent cause for recurrent urinary
      tract infection in young and middle-aged men. The selection of an appropriate
      antimicrobial agent that has optimal pharmacokinetics for urine and prostatic
      secretion and tissue is important in both entities. Fluoroquinolones possess
      several pharmacologic characteristics that favor them for treatment of urinary
      tract infection and prostatitis. The pharmacokinetics of fluoroquinolones and the
      theoretical background of drug penetration into the prostate are outlined.
      Analyzing the concentrations of various fluoroquinolones in urine, prostatic and
      seminal fluid, and in prostatic tissue, it becomes obvious that the
      fluoroquinolones differ in plasma concentrations and in their concentrations at
      these sites. Nevertheless, overall, the concentrations at the site of infection
      of most of the fluoroquinolones should be sufficient for the treatment of chronic
      bacterial prostatitis and vesiculitis and recurrent urinary tract infection in
      men caused by susceptible pathogens.

PMID- 15260936
TI  - Prostatitis: the cost of disease and therapies to patients and society.
AB  - Prostatitis is an elusive clinical phenomenon that has become a synonymous term
      to describe a plethora of lower urinary tract symptoms in men including urinary
      problems, sexual dysfunction, and pelvic pain. Although symptom presentation has
      been standardized, an accurate, consistent clinical diagnosis continues to be
      elusive at best. As a result, recurrence is common, quality of life is
      compromised, and the patients and society feel the cost of this disease.

PMID- 15260937
TI  - Minimally invasive therapies for prostatitis.
AB  - A plethora of reports describe a number of promising new minimally invasive
      treatment modalities available to patients with chronic prostatitis. This article
      reviews these studies, with most evaluating treatments using heat or
      intraprostatic injection. The results are difficult to compare because of the
      inconsistencies in study design, modalities of treatment, and outcome measures.
      Standard criteria for assessing symptom severity in chronic prostatitis recently
      have been developed and prospective clinical trials are underway to evaluate
      minimally invasive therapies for this debilitating condition. Until definitive
      data from these trials are available, minimally invasive therapies most likely
      will continue to be empirical and not a standard of care.

PMID- 15260938
TI  - Pharmacologic prophylaxis of post-traumatic stress disorder.

PMID- 15260940
TI  - Anxiety disorders and schizophrenia.
AB  - Anxiety symptoms and disorders have long been described in schizophrenia. This
      article reviews the epidemiology, phenomenology, and neurobiologic underpinnings
      of comorbid anxiety symptoms and disorders in schizophrenia. Recent literature
      was obtained by Medline searches using key words relating to schizophrenia and
      anxiety symptoms or disorders. There is some evidence that anxiety may be a core
      symptom dimension in schizophrenia, although further work is required. There is
      evidence that comorbid obsessive-compulsive disorder, panic disorder, post
      traumatic stress disorder, and social anxiety disorder are all more common than
      expected by chance in schizophrenia, although additional work is needed to
      determine the mechanisms that underlie these associations and their clinical
      implications. In the interim, however, the data emphasize the importance of
      assessing and treating comorbid anxiety symptoms and disorders in schizophrenia.

PMID- 15260939
TI  - Genetics of anxiety disorders.
AB  - There is considerable evidence that genetic determinants play a major role in the
      etiology of anxiety. Investigations into susceptibility genes for anxiety are
      well underway, particularly for panic disorder and obsessive-compulsive disorder
      and more broadly defined anxiety-related traits, such as neuroticism and harm
      avoidance. This review will discuss some of the core issues related to diagnosis
      and molecular genetic methodology, followed by a review of recent molecular
      genetic findings for anxiety. The authors will attempt to highlight the numerous
      convergent and exciting findings. Given the rapid acceleration in knowledge of
      the human genome, a more definitive understanding of the genetic roots of these
      complex conditions may be anticipated in the relatively near future.

PMID- 15260941
TI  - Ethics of research on survivors of trauma.
AB  - Essential elements of all research include balance of risks and benefits,
      unbiased selection of research samples, and assurance of the rights of individual
      participants. This paper highlights some key ethical issues and summarizes recent
      evidence relating to participation in, and conduct of, trauma-focused studies
      with special reference to vulnerable populations (eg, women and children,
      refugees, survivors of human rights violations, and survivors of trauma in the
      developing world). A concise ethical framework, rather than rigid guidelines
      (that may not be applicable to all trauma studies), may be a more useful point of
      reference for investigators and ethics committees or institutional review boards.
      Despite the increased empiric data available to inform ethical dilemmas regarding
      trauma research, more cost-burden analysis research in varying trauma populations
      and careful investigation of factors that contribute to risk and benefit is
      required.

PMID- 15260942
TI  - Integrating pharmacotherapy and psychotherapy in the management of anxiety
      disorders.
AB  - Anxiety disorders are among the most prevalent psychiatric conditions throughout
      the world, and they are responsible for considerable morbidity and functional
      impairment. Patients with these disorders make extensive use of medical
      resources, not only through their use of the mental health system but by frequent
      utilization of primary care and emergency medical services. Although it is common
      clinical practice to combine pharmacotherapy and psychotherapy, some researchers
      have argued that this has not been shown effective in practice and is an
      inefficient use of limited mental health resources. This article will examine the
      evidence supporting integrative therapy for the major Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision anxiety disorders and
      discuss clinical considerations surrounding the use of combined therapies for
      anxiety.

PMID- 15260943
TI  - The molecular neuroimaging of anxiety disorders.
AB  - This paper reviews the molecular neuroimaging of anxiety disorders, and attempts
      to put recent advances in the context of previous findings. Knowledge of the
      metabolic correlates of symptom severity and treatment response in obsessive
      compulsive disorder has been significantly extended, particularly response to
      selective serotonin reuptake inhibitor medication. However, the first
      neuroreceptor studies of serotonin transporter availability in obsessive
      compulsive disorder have proved inconclusive, and further studies are
      anticipated. Reduced 5-HT1A receptor binding has been reported in panic disorder.
      Recent findings have extended the knowledge of hippocampal abnormalities in post
      traumatic stress disorder, and have highlighted the complexity of the association
      between cortisol and the hippocampus in this disorder.

PMID- 15260944
TI  - Patient and family attitudes toward schizophrenia treatment.
AB  - Patient and family member attitudes toward illness, psychopharmacologic and
      nonpharmacologic treatments in schizophrenia, as well as their attitudes toward
      psychiatric research are reviewed here. The authors' recent work investigating
      patient and family member attitudes toward illness, medication, and a new method
      of receiving medication via surgical implants is also presented. The authors
      highlight the importance of understanding patient attitudes so that individual
      treatment plans and new treatments for schizophrenia can be facilitated. The
      important contribution of family members in caring for their loved ones is also
      emphasized. Patient participation in biomedical research is also discussed in the
      context of guiding the treatment of schizophrenia.

PMID- 15260945
TI  - Evaluating and treating the prodromal stage of schizophrenia.
AB  - Identification of a person in the prodromal stage of schizophrenia, before the
      onset of the first episode of psychosis, provides an opportunity for early,
      potentially preventative, interventions. Recent attempts to develop "at risk" or
      "prodromal syndrome" diagnostic criteria have proved to be successful at
      identifying individuals at high risk for psychosis. Preliminary investigations
      find that pharmacologic and psychotherapeutic interventions may reduce the risk
      of psychosis in "at risk" individuals, but until more is known, current treatment
      guidelines recommend close monitoring, therapeutic interventions that address
      identified problems, including supportive or cognitive therapies to reduce the
      functional consequences of the presenting symptoms, family interventions to
      reduce family distress and improve coping, and intervention with schools to
      decrease likelihood of school failure. Pharmacologic intervention targeting the
      prodromal symptoms is not recommended, given the uncertain risk-benefit ratio.

PMID- 15260946
TI  - Approaches for adolescents with an affected family member with schizophrenia.
AB  - Prospective studies of adolescents at risk for schizophrenia (high-risk studies)
      can shed light on the possible premorbid precursors of schizophrenia. Recent
      studies have provided evidence of neurobehavioral, brain structural, physiologic,
      and neurochemical deficits in adolescent nonpsychotic high-risk relatives that
      may date back to childhood or earlier. These results are collectively providing a
      critical window into the inter-relationships between genetic predisposition,
      neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent
      approaches are inherently powerful in mutually informing each other in enriching
      the knowledge of the risk factors that predict the eventual onset of
      schizophrenia. Defining such reliable predictors of the onset of schizophrenia
      may provide us with the tools to better understand the etiology and
      pathophysiology of the illness, and may pave the way for innovative methods of
      treatment and possibly prevention. The authors review the relevant literature in
      this promising field of inquiry and summarize recent findings from high-risk
      studies.

PMID- 15260947
TI  - The genes for schizophrenia: finally a breakthrough?
AB  - A number of susceptibility genes for schizophrenia have recently been identified.
      They have engendered excitement because replicate studies have attained greater
      consistency than in the past. In this review, we outline gene mapping methods,
      and briefly review their strengths and challenges. We also evaluate peer-reviewed
      genetic association studies that have implicated six selected genes: catechol-O
      methyl transferase (COMT), neuregulin 1 (NRG1), dysbindin (DTNBP1), regulator of
      G-protein signaling 4 (RGS4), and G72 and D-amino-acid oxidase (DAAO). The
      available supporting evidence is variable. Though credible evidence is available
      for all of these genes, it is strongest for NRG1 and DTNBP1. Further studies,
      particularly exhaustive analyses of all polymorphisms at each locus, meta
      analyses, and investigations of the likely function of risk alleles (variants)
      are desirable.

PMID- 15260948
TI  - Paying the price at the pump: dystonia from mutations in a Na+/K+ -ATPase.
AB  - Dystonia is a disorder of involuntary sustained muscle contraction, which usually
      affects a focal region of the body but may be generalized and results in twisting
      contorted movements or abnormal postures. Several clinical subtypes of dystonia
      have been delineated and many have a strong inherited basis. In this issue of
      Neuron, de Carvalho Aguiar and colleagues report the identification of missense
      mutations in the gene for the Na+/K+ -ATPase alpha3 subunit (ATP1A3) as a cause
      of rapid-onset dystonia-parkinsonism (RDP, DYT12).

PMID- 15260949
TI  - New roles for an old molecule in axon-glial interaction.
AB  - Axons need to be above a minimum size before they can be ensheathed by myelin
      forming glia. But it has generally been assumed that the axonal signals that
      initiate myelination, whatever they are, would act similarly in both the CNS and
      the PNS. The surprising finding of Chan et al. in this issue of Neuron is that
      NGF can act as a regulator of ensheathment but that it has opposite effects on
      CNS and PNS axons.

PMID- 15260950
TI  - Close encounters: how cortical neurons find and connect to their correct synaptic
      partners depends on the cell type.
AB  - In this issue of Neuron, Stepanyants et al. embark on quantitative analyses of
      the axonal and dendritic arbors of cortical neurons. They test whether the paths
      taken by axons actually bring them closer to their true synaptic partners than
      they would have gotten by chance encounters based on the same axon trajectories.
      The results depend on the type of presynaptic neuron. Inhibitory cells take paths
      that explicitly link them to their actual partners while excitatory axons are as
      likely to have close encounters with actual partners as with other neurons. These
      results suggest that the mechanisms for selectivity depend on the type of
      presynaptic neuron.

PMID- 15260951
TI  - The assembly of neural circuits.

PMID- 15260952
TI  - Problems and solutions for circuits and synapses in Parkinson's disease.

PMID- 15260953
TI  - Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid
      onset dystonia parkinsonism.
AB  - Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal
      dominant movement disorder with variable expressivity and reduced penetrance
      characterized by abrupt onset of dystonia, usually accompanied by signs of
      parkinsonism. The sudden onset of symptoms over hours to a few weeks, often
      associated with physical or emotional stress, suggests a trigger initiating a
      nervous system insult resulting in permanent neurologic disability. We report the
      finding of six missense mutations in the gene for the Na+/K+ -ATPase alpha3
      subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and
      structural analysis of the protein suggest that these mutations impair enzyme
      activity or stability. This finding implicates the Na+/K+ pump, a crucial protein
      responsible for the electrochemical gradient across the cell membrane, in
      dystonia and parkinsonism.

PMID- 15260954
TI  - Multisensory integration of looming signals by rhesus monkeys.
AB  - Looming objects produce ecologically important signals that can be perceived in
      both the visual and auditory domains. Using a preferential looking technique with
      looming and receding visual and auditory stimuli, we examined the multisensory
      integration of looming stimuli by rhesus monkeys. We found a strong attentional
      preference for coincident visual and auditory looming but no analogous preference
      for coincident stimulus recession. Consistent with previous findings, the effect
      occurred only with tonal stimuli and not with broadband noise. The results
      suggest an evolved capacity to integrate multisensory looming objects.

PMID- 15260955
TI  - NGF controls axonal receptivity to myelination by Schwann cells or
      oligodendrocytes.
AB  - Axons dictate whether or not they will become myelinated in both the central and
      peripheral nervous systems by providing signals that direct the development of
      myelinating glia. Here we identify the neurotrophin nerve growth factor (NGF) as
      a potent regulator of the axonal signals that control myelination of TrkA
      expressing dorsal root ganglion neurons (DRGs). Unexpectedly, these NGF-regulated
      axonal signals have opposite effects on peripheral and central myelination,
      promoting myelination by Schwann cells but reducing myelination by
      oligodendrocytes. These findings indicate a novel role for growth factors in
      regulating the receptivity of axons to myelination and reveal that different
      axonal signals control central and peripheral myelination.

PMID- 15260956
TI  - Dap160/intersectin acts as a stabilizing scaffold required for synaptic
      development and vesicle endocytosis.
AB  - We describe the isolation of mutations in dynamin-associated protein 160 kDa
      (dap160), the Drosophila homolog of intersectin, a putative adaptor for proteins
      involved in endocytosis, cytoskeletal regulation, and signaling. We show that
      partial loss-of-function mutants display temperature-sensitive (ts) paralysis,
      whereas null mutants show ts defects in endocytosis. Loss-of-function mutants
      exhibit bouton overgrowth at larval neuromuscular junctions (NMJs), but evoked
      neurotransmission is normal. Mutant NMJs show a mild endocytic defect at 22
      degrees C, which is strongly enhanced at 34 degrees C. The levels of dynamin,
      synaptojanin and endophilin are severely reduced in dap160 mutant NMJs,
      suggesting that Dap160 serves to stabilize an endocytic macromolecular complex.
      Electron microscopy reveals fewer vesicles, aberrant large vesicles, and an
      accumulation of endocytic intermediates at active and periactive zones in mutant
      terminals. Our data suggest that Dap160, like dynamin, is involved in synaptic
      vesicle retrieval at active and periactive zones.

PMID- 15260957
TI  - Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity
      endocytosis and normal synaptic growth.
AB  - Dap160/Intersectin is a multidomain adaptor protein that colocalizes with
      endocytic machinery in the periactive zone at the Drosophila NMJ. We have
      generated severe loss-of-function mutations that eliminate Dap160 protein from
      the NMJ. dap160 mutant synapses have decreased levels of essential endocytic
      proteins, including dynamin, endophilin, synaptojanin, and AP180, while other
      markers of the active zone and periactive zone are generally unaltered.
      Functional analyses demonstrate that dap160 mutant synapses are unable to sustain
      high-frequency transmitter release, show impaired FM4-64 loading, and show a
      dramatic increase in presynaptic quantal size consistent with defects in synaptic
      vesicle recycling. The dap160 mutant synapse is grossly malformed with abundant,
      highly ramified, small synaptic boutons. We present a model in which Dap160
      scaffolds both endocytic machinery and essential synaptic signaling systems to
      the periactive zone to coordinately control structural and functional synapse
      development.

PMID- 15260958
TI  - Subunit rules governing the sorting of internalized AMPA receptors in hippocampal
      neurons.
AB  - Removal of synaptic AMPA receptors is important for synaptic depression. Here, we
      characterize the roles of individual subunits in the inducible redistribution of
      AMPA receptors from the cell surface to intracellular compartments in cultured
      hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not
      GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced
      internalization, homomeric GluR2 enters the recycling pathway, but following
      NMDA, GluR2 is diverted to late endosomes/lysosomes. In contrast, GluR1 remains
      in the recycling pathway, and GluR3 is targeted to lysosomes regardless of NMDA
      receptor activation. Interaction with NSF plays a role in regulated lysosomal
      targeting of GluR2. GluR1/GluR2 heteromeric receptors behave like GluR2 homomers,
      and endogenous AMPA receptors show differential activity-dependent sorting
      similar to homomeric GluR2. Thus, GluR2 is a key subunit that controls recycling
      and degradation of AMPA receptors after internalization.

PMID- 15260959
TI  - Eye opening rapidly induces synaptic potentiation and refinement.
AB  - NMDA receptor (NMDAR)-mediated increases in AMPA receptor (AMPAR) currents are
      associated with long-term synaptic potentiation (LTP). Here, we provide evidence
      that similar changes occur in response to normal increases in sensory stimulation
      during development. Experiments discriminated between eye opening-induced and age
      dependent changes in synaptic currents. At 6 hr after eye opening (AEO), a
      transient population of currents mediated by NR2B-rich NMDARs increase
      significantly, and silent synapses peak. Sustained increases in evoked and
      miniature AMPAR currents occur at 12 hr AEO. Significant changes in AMPAR:NMDAR
      evoked current ratios, contacts per axon, and inputs per cell are present at 24
      hr AEO. The AMPAR current changes are those seen in vitro during NMDAR-dependent
      LTP. Here, they are a consequence of eye opening and are associated with a new
      wave of synaptic refinement. These data also suggest that new NR2B-rich NMDAR
      currents precede and may initiate this developmental synaptic potentiation and
      functional tuning.

PMID- 15260960
TI  - Class-specific features of neuronal wiring.
AB  - Brain function relies on specificity of synaptic connectivity patterns among
      different classes of neurons. Yet, the substrates of specificity in complex
      neuropil remain largely unknown. We search for imprints of specificity in the
      layout of axonal and dendritic arbors from the rat neocortex. An analysis of 3D
      reconstructions of pairs consisting of pyramidal cells (PCs) and GABAergic
      interneurons (GIs) revealed that the layout of GI axons is specific. This
      specificity is manifested in a relatively high tortuosity, small branch length of
      these axons, and correlations of their trajectories with the positions of
      postsynaptic neuron dendrites. Axons of PCs show no such specificity, usually
      taking a relatively straight course through neuropil. However, wiring patterns
      among PCs hold a large potential for circuit remodeling and specificity through
      growth and retraction of dendritic spines. Our results define distinct class
      specific rules in establishing synaptic connectivity, which could be crucial in
      formulating a canonical cortical circuit.

PMID- 15260961
TI  - Amphetamine modulates human incentive processing.
AB  - Research suggests that psychostimulants can physiologically alter dopamine
      kinetics in the ventral striatum (VS) and psychologically enhance mood and
      attention. Using event-related functional magnetic resonance imaging (fMRI), we
      conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the
      effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity
      and affect during incentive processing. In two counterbalanced scanning sessions
      60-180 min after ingesting AMPH or PLAC, 8 healthy volunteers played a game
      involving anticipation and receipt of monetary gains and losses. Group and volume
      of interest analyses suggested that by enhancing tonic over phasic activation,
      AMPH treatment "equalized" levels of VS activity and positive arousal during
      anticipation of both gain and loss. These findings suggest that therapeutic
      effects of amphetamine on incentive processing may involve reducing the
      difference between anticipation of gains and losses.

PMID- 15260962
TI  - Integration of letters and speech sounds in the human brain.
AB  - Most people acquire literacy skills with remarkable ease, even though the human
      brain is not evolutionarily adapted to this relatively new cultural phenomenon.
      Associations between letters and speech sounds form the basis of reading in
      alphabetic scripts. We investigated the functional neuroanatomy of the
      integration of letters and speech sounds using functional magnetic resonance
      imaging (fMRI). Letters and speech sounds were presented unimodally and bimodally
      in congruent or incongruent combinations. Analysis of single-subject data and
      group data aligned on the basis of individual cortical anatomy revealed that
      letters and speech sounds are integrated in heteromodal superior temporal cortex.
      Interestingly, responses to speech sounds in a modality-specific region of the
      early auditory cortex were modified by simultaneously presented letters. These
      results suggest that efficient processing of culturally defined associations
      between letters and speech sounds relies on neural mechanisms similar to those
      naturally evolved for integrating audiovisual speech.

PMID- 15260963
TI  - Prefrontal cortex guides context-appropriate responding during language
      production.
AB  - Although language processing is thought to frequently require cognitive control,
      little is known about the cognitive and neural basis of the control of language.
      Here, we demonstrate that processing of context by the PFC plays an important
      role in the control of language comprehension and production. Using a missing
      letter paradigm and fMRI, we found that increased activation in the PFC (but not
      in posterior regions), while encoding and maintaining context information,
      predicted context-appropriate responses. Furthermore, greater selection demands
      increased activity during responding in the same regions engaged during the
      encoding and maintenance of context. Overall, as in other cognitive task domains,
      these results suggest that PFC context processing plays an important role in the
      control of language.

PMID- 15260964
TI  - The Making of an siRNA.
AB  - An array of gene silencing pathways share a common early step: Dicer cleaves
      double-stranded RNA (dsRNA) into approximately 20-25 nucleotide fragments that
      direct the silencing machinery to specific targets. A recent report in Cell
      reveals how Dicer's two RNase III domains collaborate during dsRNA processing and
      sets the stage for a deeper understanding of Dicer's roles in later phases of
      silencing complex assembly.

PMID- 15260965
TI  - Replication factors license exonuclease I in mismatch repair.
AB  - A key question in the eukaryotic mismatch repair field is how strand excision is
      coordinated with mismatch recognition. In a recent issue of Molecular Cell,
      Dzantiev et al. present evidence that the replication factors PCNA and RFC
      modulate the directionality of EXOI-mediated excision.

PMID- 15260966
TI  - Necessity's sharp pinch.
AB  - In a recent issue of Cell, Hughes and coworkers (Mnaimneh et al., 2004) provide a
      great leap forward in the analysis of essential yeast genes by constructing a
      strain set that expresses each essential gene from a tetracycline-regulatable
      promoter.

PMID- 15260967
TI  - Sef: a MEK/ERK catcher on the Golgi.
AB  - Subcellular compartmentalization is an emerging paradigm in signaling pathways
      including the Ras/MAPK pathway. In a recent issue of Developmental Cell, Torii et
      al. (2004) characterize a new MAPK scaffold, Sef, that resides on the Golgi
      apparatus, binds active MEK/ERK complexes, and permits signaling to cytosolic
      substrates but not nuclear targets.

PMID- 15260968
TI  - JNK regulates expression and autocrine signaling of TGF-beta1.
AB  - TGF-beta1 can induce its own expression by an autoregulatory mechanism. In this
      issue of Molecular Cell, Ventura et al. (2004) show, using JNK-deficient
      fibroblasts, that JNK negatively regulates TGF-beta1 gene expression and,
      consequently, autocrine TGF-beta signaling. The results highlight the
      contributions of JNK signaling in the control of TGF-beta expression and
      signaling, and of autocrine TGF-beta signaling in the JNK-regulated changes in
      cell behavior.

PMID- 15260969
TI  - AtXRN4 degrades mRNA in Arabidopsis and its substrates include selected miRNA
      targets.
AB  - Messenger RNA degradation is an essential step in gene expression that can be
      regulated by siRNAs or miRNAs. However, most of our knowledge of in vivo
      eukaryotic mRNA degradation mechanisms derives from Saccharomyces cerevisiae,
      which lacks miRNAs and RNAi capability. Using reverse genetic and microarray
      analyses, we have identified multiple substrates of AtXRN4, the Arabidopsis
      homolog of the major yeast mRNA degrading exoribonuclease, Xrn1p. Insertional
      mutation of AtXRN4 leads to accumulation of the 3' end of several mRNAs, in a
      manner that correlates with increased stability of the 3' end, and is reversed
      following complementation with AtXRN4. Moreover, 3' products of miRNA-mediated
      cleavage of SCARECROW-LIKE transcripts and several other miRNA target transcripts
      are among those that accumulate in xrn4 mutants. The demonstration that an Xrn1p
      homolog degrades mRNA in a multicellular eukaryote and contributes to the miRNA
      mediated decay pathway of selected targets has implications for XRNs in other
      organisms.

PMID- 15260970
TI  - Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.
AB  - Argonaute proteins associate with small RNAs that guide mRNA degradation,
      translational repression, or a combination of both. The human Argonaute family
      has eight members, four of which (Ago1 through Ago4) are closely related and
      coexpressed in many cell types. To understand the biological function of the
      different Ago proteins, we set out to determine if Ago1 through Ago4 are
      associated with miRNAs as well as RISC activity in human cell lines. Our results
      suggest that miRNAs are incorporated indiscriminately of their sequence into Ago1
      through Ago4 containing microRNPs (miRNPs). Purification of the FLAG/HA-epitope
      tagged Ago containing complexes from different human cell lines revealed that
      endonuclease activity is exclusively associated with Ago2. Exogenously introduced
      siRNAs also associate with Ago2 for guiding target RNA cleavage. The specific
      role of Ago2 in guiding target RNA cleavage was confirmed independently by siRNA
      based depletion of individual Ago members in combination with a sensitive
      positive-readout reporter assay.

PMID- 15260971
TI  - Molecular architecture of the S. cerevisiae SAGA complex.
AB  - The Saccharomyces cerevisiae SAGA complex is a multifunctional coactivator that
      regulates transcription by RNA polymerase II. The 3D structure of SAGA, revealed
      by electron microscopy, is formed by five modular domains and shows a high degree
      of structural conservation to human TFTC, reflecting their related subunit
      composition. The positions of several SAGA subunits were mapped by immunolabeling
      and by analysis of mutant complexes. The Taf (TBP-associated factor) subunits,
      shared with TFIID, occupy a central region in SAGA and form a similar structure
      in both complexes. The locations of two histone fold-containing core subunits,
      Spt7 and Ada1, are consistent with their role in providing a SAGA-specific
      interface with the Tafs. Three components that perform distinct regulatory
      functions, Spt3, Gcn5, and Tra1, are spatially separated, underscoring the
      modular nature of the complex. Our data provide insights into the molecular
      architecture of SAGA and imply a functional organization to the complex.

PMID- 15260972
TI  - AP endonuclease-independent DNA base excision repair in human cells.
AB  - The paradigm for repair of oxidized base lesions in genomes via the base excision
      repair (BER) pathway is based on studies in Escherichia coli, in which AP
      endonuclease (APE) removes all 3' blocking groups (including 3' phosphate)
      generated by DNA glycosylase/AP lyases after base excision. The recently
      discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the
      previously characterized OGG1 and NTH1, generate DNA strand breaks with 3'
      phosphate termini. Here we show that in mammalian cells, removal of the 3'
      phosphate is dependent on polynucleotide kinase (PNK), and not APE. NEIL1 stably
      interacts with other BER proteins, DNA polymerase beta (pol beta) and DNA ligase
      IIIalpha. The complex of NEIL1, pol beta, and DNA ligase IIIalpha together with
      PNK suggests coordination of NEIL1-initiated repair. That NEIL1/PNK could also
      repair the products of other DNA glycosylases suggests a broad role for this APE
      independent BER pathway in mammals.

PMID- 15260973
TI  - The compact chromatin structure of a Ty repeated sequence suppresses
      recombination hotspot activity in Saccharomyces cerevisiae.
AB  - Recombination between repeated DNA sequences can have drastic consequences on the
      integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet
      the mechanism that prevents recombination between them is currently unknown. Ty
      elements, the main family of dispersed repeats in Saccharomyces cerevisiae,
      exhibit low levels of exchange. Other regions in the genome have relatively high
      rates of meiotic recombination (hotspots). We show that a Ty element adjacent to
      the HIS4 recombination hotspot substantially reduces its activity, eliminating
      local DSB formation. We demonstrate that the Ty has a closed (nuclease
      insensitive) chromatin configuration that is also imposed on the flanking DNA
      sequences. The compact chromatin structure is determined by sequences at the N
      terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores
      both open chromatin conformation and DSB formation. The chromatin configuration
      of Ty elements precludes initiation of recombination, thus preventing potentially
      lethal exchanges between repeated sequences.

PMID- 15260974
TI  - The cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer.
AB  - The human cytomegalovirus DNA polymerase consists of a catalytic subunit, UL54,
      and a presumed processivity factor, UL44. We have solved the crystal structure of
      residues 1-290 of UL44 to 1.85 A resolution by multiwavelength anomalous
      dispersion. The structure reveals a dimer of UL44 in the shape of a C clamp. Each
      monomer of UL44 shares its overall fold with other processivity factors,
      including herpes simplex virus UL42, which is a monomer that binds DNA directly,
      and the sliding clamp, PCNA, which is a trimer that surrounds DNA, although these
      proteins share no obvious sequence homology. Analytical ultracentrifugation and
      gel filtration measurements demonstrated that UL44 also forms a dimer in
      solution, and substitution of large hydrophobic residues along the homodimer
      interface with alanine disrupted dimerization and decreased DNA binding. UL44
      represents a hybrid processivity factor as it binds DNA directly like UL42, but
      forms a C clamp that may surround DNA like PCNA.

PMID- 15260975
TI  - A dimerized coiled-coil domain and an adjoining part of geminin interact with two
      sites on Cdt1 for replication inhibition.
AB  - Geminin is a cellular protein that associates with Cdt1 and inhibits Mcm2-7
      loading during S phase. It prevents multiple cycles of replication per cell cycle
      and prevents episome replication. It also directly inhibits the HoxA11
      transcription factor. Here we report that geminin forms a parallel coiled-coil
      homodimer with atypical residues in the dimer interface. Point mutations that
      disrupt the dimerization abolish interaction with Cdt1 and inhibition of
      replication. An array of glutamic acid residues on the coiled-coil domain surface
      interacts with positive charges in the middle of Cdt1. An adjoining region
      interacts independently with the N-terminal 100 residues of Cdt1. Both
      interactions are essential for replication inhibition. The negative residues on
      the coiled-coil domain and a different part of geminin are also required for
      interaction with HoxA11. Therefore a rigid cylinder with negative surface charges
      is a critical component of a bipartite interaction interface between geminin and
      its cellular targets.

PMID- 15260976
TI  - Direct binding of cholesterol to the purified membrane region of SCAP: mechanism
      for a sterol-sensing domain.
AB  - Mammalian cells control their membrane composition by regulating the vesicular
      transport of membrane-bound sterol regulatory element binding proteins (SREBPs)
      from endoplasmic reticulum (ER) to Golgi. Transport is blocked by cholesterol,
      which triggers SCAP, the SREBP escort protein, to bind to Insigs, which are ER
      retention proteins. The cholesterol trigger mechanism is unknown. Using
      recombinant SCAP purified in detergent, we show that cholesterol acts by binding
      with high affinity and specificity to the 767 amino acid octahelical membrane
      region of SCAP. This octahelical region contains a conserved pentahelical sterol
      sensing domain found in six other polytopic membrane proteins. We show that the
      membrane domain of SCAP is a tetramer and that cholesterol binding is inhibited
      by cationic amphiphiles, raising the possibility of allosteric regulation by
      positively charged phospholipids. The current studies show that cells control
      their cholesterol content through receptor-ligand interactions and not through
      changes in the physical properties of the membrane.

PMID- 15260977
TI  - JNK regulates autocrine expression of TGF-beta1.
AB  - The c-Jun NH2-terminal kinase (JNK) has been implicated in the function of
      transforming growth factor beta (TGF-beta). To test the role of JNK, we examined
      the effect of compound disruption of the murine genes that encode the
      ubiquitously expressed isoforms of JNK (Jnk1 and Jnk2). We report that JNK
      deficient fibroblasts isolated from Jnk1-/- Jnk2-/- mice constitutively express
      TGF-beta1. Complementation studies demonstrate that JNK is a repressor of Tgf
      beta1 gene expression. This mechanism of regulation of TGF-beta1 expression by
      JNK represents an unexpected form of cross-talk between two important signaling
      pathways. Together, these data demonstrate that the JNK pathway may contribute to
      the regulation of autocrine TGF-beta1-mediated biological responses in vivo.

PMID- 15260978
TI  - A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases.
AB  - Phosphodiesterases (PDEs) comprise a family of enzymes that modulate the immune
      response, inflammation, and memory, among many other functions. There are three
      types of PDEs: cAMP-specific, cGMP-specific, and dual-specific. Here we describe
      the mechanism of nucleotide selectivity on the basis of high-resolution co
      crystal structures of the cAMP-specific PDE4B and PDE4D with AMP, the cGMP
      specific PDE5A with GMP, and the apo-structure of the dual-specific PDE1B. These
      structures show that an invariant glutamine functions as the key specificity
      determinant by a "glutamine switch" mechanism for recognizing the purine moiety
      in cAMP or cGMP. The surrounding residues anchor the glutamine residue in
      different orientations for cAMP and for cGMP. The PDE1B structure shows that in
      dual-specific PDEs a key histidine residue may enable the invariant glutamine to
      toggle between cAMP and cGMP. The structural understanding of nucleotide binding
      enables the design of new PDE inhibitors that may treat diseases in which cyclic
      nucleotides play a critical role.

PMID- 15260979
TI  - Expanded CAG repeats activate the DNA damage checkpoint pathway.
AB  - Trinucleotide repeats (TNRs) are sequences whose expansion causes several genetic
      diseases and chromosome breakage. We report a novel finding that expanded CAG
      repeats activate the DNA damage response. Mutations in yeast MEC1, RAD9, or RAD53
      genes result in increased rates of fragility of a CAG repeat tract while single
      or double deletions of RAD17 or RAD24 have only a modest effect on TNR fragility,
      indicating that signaling down the Rad9 pathway and not the Rad17-Rad24 pathway
      plays a major role in sensing and repairing CAG-tract breaks. Deletion of CHK1
      had no effect on CAG fragility, suggesting that a Chk1-mediated G2 arrest is not
      required for TNR repair. Absence of Mec1, Ddc2, Rad17, Rad24, or Rad53 also gives
      rise to increased frequency of CAG repeat contractions, indicating that
      components of the checkpoint machinery play an active role in the maintenance of
      both chromosomal integrity and repeat stability at expanded CAG sequences.

PMID- 15260980
TI  - A pre-ribosome with a tadpole-like structure functions in ATP-dependent
      maturation of 60S subunits.
AB  - Analyses of isolated pre-ribosomes yielded biochemical "snapshots" of the
      dynamic, nascent 60S and 40S subunits during their path from the nucleolus to the
      cytoplasm. Here, we present the structure of a pre-60S ribosomal intermediate
      located in the nucleoplasm. A huge dynein-related AAA-type ATPase (Rea1) and the
      Rix1 complex (Rix1-Ipi1-Ipi3) are components of an extended (approximately 45 nm
      long) pre-60S particle. Antibody crosslinking in combination with electron
      microscopy revealed that the Rea1 localizes to the "tail" region and ribosomal
      proteins to the "head" region of the elongated "tadpole-like" structure.
      Furthermore, in vitro treatment with ATP induces dissociation of Rea1 from the
      pre-60S subunits. Rea1 and the Rix1 complex could mediate ATP-dependent
      remodeling of 60S subunits and subsequent export from the nucleoplasm to the
      cytoplasm.

PMID- 15260981
TI  - Genomic run-on evaluates transcription rates for all yeast genes and identifies
      gene regulatory mechanisms.
AB  - Most studies of eukaryotic gene regulation have been done looking at mature mRNA
      levels. Nevertheless, the steady-state mRNA level is the result of two opposing
      factors: transcription rate (TR) and mRNA degradation. Both can be important
      points to regulate gene expression. Here we show a new method that combines the
      use of nylon macroarrays and in vivo radioactive labeling of nascent RNA to
      quantify TRs, mRNA levels, and mRNA stabilities for all the S. cerevisiae genes.
      We found that during the shift from glucose to galactose, most genes undergo
      drastic changes in TR and mRNA stability. However, changes in mRNA levels are
      less pronounced. Some genes, such as those encoding mitochondrial proteins, are
      coordinately regulated in mRNA stability behaving as decay regulons. These
      results indicate that, although TR is the main determinant of mRNA abundance in
      yeast, modulation of mRNA stability is a key factor for gene regulation.

PMID- 15260982
TI  - "Tie-ing" down the hematopoietic niche.
AB  - Interaction of hematopoietic stem cells (HSCs) with their particular
      microenvironment, or niche, is critical for adult hematopoiesis in the bone
      marrow (BM). Arai et al. (this issue of Cell) demonstrate that HSCs that express
      the receptor tyrosine kinase Tie2 are quiescent. Ang-1, the ligand for Tie2,
      enhanced the ability of HSCs to become quiescent and also induced their adhesion
      to bone, protecting them from stresses that suppress hematopoiesis. These data
      suggest that the Ang-1/Tie2 signaling pathway plays a crucial role in the
      maintenance of HSCs in a quiescent state in the BM niche.

PMID- 15260983
TI  - Regulation of WASP: PIP2 Pipped by Toca-1?
AB  - Cdc42 is a key regulator of cell polarity and actin dynamics. One of its
      effectors, WASP, initiates the assembly of new actin filaments. In this issue of
      Cell, show that a previously unknown regulator named Toca-1 is required for Cdc42
      to activate WASP. This discovery changes our picture of how small GTPases and
      multiple other signals converge to stimulate actin polymerization and cell
      motility.

PMID- 15260984
TI  - Going the distance, or not, with neurotrophin signals.
AB  - NGF and NT-3 both signal through TrkA receptors on the axons of developing
      sympathetic neurons, but while NGF supports survival and differentiation, NT-3
      does not. In this issue of Cell, the difference is explained as the ability of
      NGF, but not NT-3, to induce internalization and retrograde transport of
      activated TrkA.

PMID- 15260985
TI  - Polycystins: from mechanosensation to gene regulation.
AB  - Polycystin proteins have been suggested to form mechanosensory transduction
      complexes involved in a variety of biological functions including sperm
      fertilization, mating behavior, and asymmetric gene expression in different
      species. Furthermore, their dysfunction is the cause of cyst formation in human
      kidney disease. This review focuses on the pros and cons of their candidacy as
      mechanically gated channels and on recent findings that have significantly
      advanced our physiological insight.

PMID- 15260986
TI  - Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the
      bone marrow niche.
AB  - The quiescent state is thought to be an indispensable property for the
      maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their
      particular microenvironments, known as the stem cell niches, is critical for
      adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs
      expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and
      comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the
      BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced
      cobblestone formation of HSCs in vitro and maintained in vivo long-term
      repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to
      become quiescent and induced adhesion to bone, resulting in protection of the HSC
      compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1
      signaling pathway plays a critical role in the maintenance of HSCs in a quiescent
      state in the BM niche.

PMID- 15260987
TI  - Derepression by depolymerization; structural insights into the regulation of Yan
      by Mae.
AB  - Yan, an ETS family transcriptional repressor, is regulated by receptor tyrosine
      kinase signaling via the Ras/MAPK pathway. Phosphorylation and downregulation of
      Yan is facilitated by a protein called Mae. Yan and Mae interact through their
      SAM domains. We find that repression by Yan requires the formation of a higher
      order structure mediated by Yan-SAM polymerization. Moreover, a crystal structure
      of the Yan-SAM/Mae-SAM complex shows that Mae-SAM specifically recognizes a
      surface on Yan-SAM that is also required for Yan-SAM polymerization. Mae-SAM
      binds to Yan-SAM with approximately 1000-fold higher affinity than Yan-SAM binds
      to itself and can effectively depolymerize Yan-SAM. Mutations on Mae that
      specifically disrupt its SAM domain-dependent interactions with Yan disable the
      derepression function of Mae in vivo. Depolymerization of Yan by Mae represents a
      novel mechanism of transcriptional control that sensitizes Yan for regulation by
      receptor tyrosine kinases.

PMID- 15260988
TI  - Heritable integration of kDNA minicircle sequences from Trypanosoma cruzi into
      the avian genome: insights into human Chagas disease.
AB  - We demonstrate the genetic transfer of DNA between eukaryotes from different
      kingdoms. The mitochondrial kinetoplast DNA (kDNA) of the intracellular parasite
      Trypanosoma cruzi is transferred to human patients with Chagas disease. This
      transfer was reproduced experimentally in rabbits and chickens. The kDNA is
      integrated into the host genome. In the human chromosomes, five loci were
      identified as integration sites, and the beta-globin locus and LINE-1
      retrotransposons were frequently targeted. Short repeated sequences in the
      parasite and the target host DNAs favor kDNA integration by homologous
      recombination. Introduced kDNA was present in offspring of chronically infected
      rabbits and in chickens hatched from T. cruzi-inoculated eggs. kDNA incorporated
      into the chicken germline was inherited through the F2 generation in the absence
      of persistent infection. kDNA integration represents a potential cause for the
      autoimmune response that develops in a percentage of chronic Chagas patients,
      which can now be approached experimentally.

PMID- 15260989
TI  - The chromosomal passenger complex is required for chromatin-induced microtubule
      stabilization and spindle assembly.
AB  - In cells lacking centrosomes, such as those found in female meiosis, chromosomes
      must nucleate and stabilize microtubules in order to form a bipolar spindle. Here
      we report the identification of Dasra A and Dasra B, two new components of the
      vertebrate chromosomal passenger complex containing Incenp, Survivin, and the
      kinase Aurora B, and demonstrate that this complex is required for chromatin
      induced microtubule stabilization and spindle formation. The failure of
      microtubule stabilization caused by depletion of the chromosomal passenger
      complex was rescued by codepletion of the microtubule-depolymerizing kinesin
      MCAK, whose activity is negatively regulated by Aurora B. By contrast, we present
      evidence that the Ran-GTP pathway of chromatin-induced microtubule nucleation
      does not require the chromosomal passenger complex, indicating that the
      mechanisms of microtubule assembly by these two pathways are distinct. We propose
      that the chromosomal passenger complex regulates local MCAK activity to permit
      spindle formation via stabilization of chromatin-associated microtubules.

PMID- 15260990
TI  - Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP
      complex.
AB  - An important signaling pathway to the actin cytoskeleton links the Rho family
      GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless,
      these previously identified components are not sufficient to mediate Cdc42
      induced actin polymerization in a physiological context. In this paper, we
      describe the biochemical purification of Toca-1 (transducer of Cdc42-dependent
      actin assembly) as an essential component of the Cdc42 pathway. Toca-1 binds both
      N-WASP and Cdc42 and is a member of the evolutionarily conserved PCH protein
      family. Toca-1 promotes actin nucleation by activating the N-WASP-WIP/CR16
      complex, the predominant form of N-WASP in cells. Thus, the cooperative actions
      of two distinct Cdc42 effectors, the N-WASP-WIP complex and Toca-1, are required
      for Cdc42-induced actin assembly. These findings represent a significantly
      revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott
      Aldrich syndrome.

PMID- 15260991
TI  - Single cell profiling of potentiated phospho-protein networks in cancer cells.
AB  - Altered growth factor responses in phospho-protein-driven signaling networks are
      crucial to cancer cell survival and pathology. Profiles of cancer cell signaling
      networks might therefore identify mechanisms by which such cells interpret
      environmental cues for continued growth. Using multiparameter flow cytometry, we
      monitored phospho-protein responses to environmental cues in acute myeloid
      leukemia at the single cell level. By exposing cancer cell signaling networks to
      potentiating inputs, rather than relying upon the basal levels of protein
      phosphorylation alone, we could discern unique cancer network profiles that
      correlated with genetics and disease outcome. Strikingly, individual cancers
      manifested multiple cell subsets with unique network profiles, reflecting cancer
      heterogeneity at the level of signaling response. The results revealed a dramatic
      remodeling of signaling networks in cancer cells. Thus, single cell measurements
      of phospho-protein responses reveal shifts in signaling potential of a phospho
      protein network, allowing for categorizing of cell network phenotypes by
      multidimensional molecular profiles of signaling.

PMID- 15260992
TI  - Recognition of commensal microflora by toll-like receptors is required for
      intestinal homeostasis.
AB  - Toll-like receptors (TLRs) play a crucial role in host defense against microbial
      infection. The microbial ligands recognized by TLRs are not unique to pathogens,
      however, and are produced by both pathogenic and commensal microorganisms. It is
      thought that an inflammatory response to commensal bacteria is avoided due to
      sequestration of microflora by surface epithelia. Here, we show that commensal
      bacteria are recognized by TLRs under normal steady-state conditions, and this
      interaction plays a crucial role in the maintenance of intestinal epithelial
      homeostasis. Furthermore, we find that activation of TLRs by commensal microflora
      is critical for the protection against gut injury and associated mortality. These
      findings reveal a novel function of TLRs-control of intestinal epithelial
      homeostasis and protection from injury-and provide a new perspective on the
      evolution of host-microbial interactions.

PMID- 15260993
TI  - A neurotrophin signaling cascade coordinates sympathetic neuron development
      through differential control of TrkA trafficking and retrograde signaling.
AB  - A fundamental question in developmental biology is how a limited number of growth
      factors and their cognate receptors coordinate the formation of tissues and
      organs endowed with enormous morphological complexity. We report that the related
      neurotrophins NGF and NT-3, acting through a common receptor, TrkA, are required
      for sequential stages of sympathetic axon growth and, thus, innervation of target
      fields. Yet, while NGF supports TrkA internalization and retrograde signaling
      from distal axons to cell bodies to promote neuronal survival, NT-3 cannot.
      Interestingly, final target-derived NGF promotes expression of the p75
      neurotrophin receptor, in turn causing a reduction in the sensitivity of axons to
      intermediate target-derived NT-3. We propose that a hierarchical neurotrophin
      signaling cascade coordinates sequential stages of sympathetic axon growth,
      innervation of targets, and survival in a manner dependent on the differential
      control of TrkA internalization, trafficking, and retrograde axonal signaling.

PMID- 15260994
TI  - FGF22 and its close relatives are presynaptic organizing molecules in the
      mammalian brain.
AB  - Target-derived cues promote local differentiation of axons into nerve terminals
      at sites of synaptic contact. Using clustering of synaptic vesicles in cultured
      neurons as an assay, we purified putative target-derived presynaptic organizing
      molecules from mouse brain and identified FGF22 as a major active species. FGF7
      and FGF10, the closest relatives of FGF22, share this activity; other FGFs have
      distinct effects. FGF22 is expressed by cerebellar granule cells during the
      period when they receive synapses. Its receptor, FGFR2, is expressed by pontine
      and vestibular neurons when their axons (mossy fibers) are making synapses on
      granule cells. Neutralization of FGF7, -10, and -22 inhibits presynaptic
      differentiation of mossy fibers at sites of contact with granule cells in vivo.
      Inactivation of FGFR2 has similar effects. These results indicate that FGF22 and
      its relatives are presynaptic organizing molecules in the mammalian brain and
      suggest new functions for this family of signaling molecules.

PMID- 15260995
TI  - Drug testing the police: some results of urinalysis and hair analysis in a major
      US metropolitan police force.
AB  - This article presents the results of drug screening done between 1985 and 1999 by
      a police department in a major eastern American city. Drug testing data is
      presented for civilians applying for the position of police officer in response
      to public solicitations, officers-in-training who are tested at the end of a two
      year training period, and "sworn" -- i.e., working officers in the field. The
      data includes test results for both urinalysis and hair analysis. The article
      compares the outcome in relationship to the intrinsic differences in time windows
      that the two testing technologies address, and assesses the efficacy of the
      technologies for detection of drug use, and the differences in detection rates
      attributable to each. The urinalysis findings show that of the three categories
      (police applicants, in-training officers, and working officers) applicants have
      drug-positive urinalyses about 2.8 times the rate of working police officers and
      at 16 times the rate for probationary officers. This pattern apparently holds
      true regardless of the size of the tested pool of personnel. Probationary
      officers in every case have the lowest rates of positive urine test results,
      applicants have the highest, and working officers occupy the middle ground. Hair
      analysis, which examines a larger time "window" than urinalysis, shows a higher
      prevalence rate than does urinalysis. The mean rate for hair analysis drug
      positive specimens was found to be 1.36 times that for urinalysis. Consistent
      with the urinalysis results, the applicant pool tested at rates 2-3 times higher
      when using hair analysis than the probationary officers.

PMID- 15260996
TI  - Changing patterns of female suicide: 1986-2000.
AB  - A study was undertaken of the rates and methods of female suicide observed at the
      Forensic Science Centre in South Australia over a 15 year period from 1986 to
      2000. A total of 609 cases of female suicide were found (age range= 13-88 yrs;
      mean= 44 yrs), with 249 drug overdoses, 114 hangings, 100 deaths due to carbon
      monoxide (CO) toxicity, 40 drownings, 35 firearm deaths and 71 miscellaneous
      deaths (including deaths due to self-immolation, jumping from heights and incised
      wounds). The most common age range was 26-50 yrs in all categories except for
      drowning where victims tended to be older. While overall suicide rates in females
      remained unchanged, with no changes in the rates at different ages, significant
      increases in hanging and CO deaths occurred over all age groups (p < 0.05), with
      significant falls in drug overdose deaths in the 10-25 year age group (p < 0.01),
      and significant overall falls in suicides due to gunshot wounds (p < 0.05). No
      changes were observed in female suicides due to drowning. This study has
      demonstrated, therefore, that although no changes in overall suicide rates for
      females occurred, there have been alterations in the types of methods being used.
      Although drug related deaths remained the largest category, hanging deaths, which
      were once uncommon in females, have increased markedly.

PMID- 15260997
TI  - Trans-metatarsal amputation as a complication of child sexual abuse.
AB  - A case of chronic physical abuse and acute sexual abuse via anal penetration
      complicated with disseminated intravascular coagulation (DIC), acute respiratory
      distress syndrome (ARDS), and subsequent bilateral trans-metatarsal amputation is
      reported. A 13-year-old male presented with old cigarette burns on his chest and
      acute anal laceration. Four days after laceration repair, he developed DIC and
      ARDS. The child had to undergo bilateral trans-metatarsal amputation. Due to the
      systemic defects of the child protection system in Turkey, sexual and physical
      abuse were recognized by medical personnel 45 days after admission, child
      protective services never got involved, and prosecution failed to punish the
      perpetrator(s) of this extreme victimization. This is the only reported case of
      bilateral trans-metatarsal amputation due to sexual abuse complicated with DIC
      and ARDS. Social and medico-legal management of sexual abuse is suboptimal in
      Turkey. Within that context, professionals should be trained on how to recognize,
      assess, diagnose and manage victims of child abuse and neglect.

PMID- 15260998
TI  - The end of life decisions -- should physicians aid their patients in dying?
AB  - Decisions pertaining to end of life whether legalized or otherwise, are made in
      many parts of the world but not reported on account of legal implications. The
      highly charged debate over voluntary euthanasia and physician assisted suicide
      was brought into the public arena again when two British doctors confessed to
      giving lethal doses of drugs to hasten the death of terminally ill patients. Lack
      of awareness regarding the distinction between different procedures on account of
      legal status granted to them in some countries is the other area of concern. Some
      equate withdrawal of life support measures to physician assisted suicide whereas
      physician assisted suicide is often misinterpreted as euthanasia. Debate among
      the medical practitioners, law makers and the public taking into consideration
      the cultural, social and religious ethos will lead to increased awareness, more
      safeguards and improvement of medical decisions concerning the end of life.
      International Human Rights Law can provide a consensual basis for such a debate
      on euthanasia.

PMID- 15260999
TI  - Medicolegal evaluation of vascular injuries of limbs in Turkey.
AB  - This study evaluated 372 cases of post-traumatic extremity vessel lesions, for
      which the Forensic Medicine Council, Istanbul, Turkey prepared medicolegal
      evaluation reports between 1998 and 2000. The study group (n = 372) comprised of
      346 men (93.0%) and 26 women (6.9%), and their ages ranged between 6 and 73 years
      (30.18 +/- 6.13). There were 378 artery (74.5%), and 131 vein injuries (25.5%)
      out of a total of 509 limb vascular injuries. The most frequently injured
      arteries and veins were the femoral artery (n = 73), and the deep femoral vein (n
      = 41), respectively. The causes of injuries were as follows: cutting and stabbing
      complements, in 160 cases (43.0%); gunshots in 136 cases (36.6%); traffic
      accidents in 52 cases (14%); work accidents in 23 cases (6.2%); and blunt trauma
      in one case (0.3%). These injuries were accompanied by local nerve lesions
      (27.1%), local bone lesions (37.1%), and injuries to other organs (11.0%). The
      medicolegal assessments by the Forensic Medicine Council showed that there were
      risk of death in 371 cases. Additionally, there was 'organ dysfunction' in 37
      (9.9%) and 'organ loss' in 53 (14.2%) cases. The results of this study suggested
      that the main causes of severe vascular injuries (i.e. those accompanied by bone
      and nerve lesions) had serious consequences such as amputation, permanent
      disorders or loss of function and were caused by gunshot and traffic accidents.

PMID- 15261000
TI  - The use of clinical CCT images in the forensic examination of closed head
      injuries.
AB  - The forensic evaluation of clinical cranial computed tomographies (CCT)
      frequently is the only reliable source of morphological evidence in head injuries
      when the injured individual survives or when death is delayed and autopsy
      findings are characterized by secondary changes. We have reviewed 21 cases where
      clinical CCT examinations were used to establish a medico-legal diagnosis. In 18
      cases falls (n = 13) could be distinguished from blows (n = 5) due to the
      presence and/or absence of coup and contrecoup lesions and linear or depressed
      skull fractures. In two cases the striking object could be identified by digital
      superimposition. The minimum number of blows could be determined in 1 case. Only
      in 3 remaining cases the results were inconclusive. In our experience, CCT scans
      provide an important source of information for the forensic expert. To have
      unbiased access to these information, it is useful to evaluate the CT scans
      personally which requires a basic knowledge of traumatic changes found on
      radiographs.

PMID- 15261001
TI  - Suicide methods in the elderly in South Australia 1981-2000.
AB  - The files of the Forensic Science Centre in Adelaide, Australia were examined
      over a 20-year period from 1981 to 2000 for cases of suicide in individuals aged
      65 years and over. A total of 445 cases were found (13.8% of all suicides) with
      an age range of 65-94 years (average= 73.5 years). All cases had undergone full
      autopsies and police investigation. There were significantly more male than
      female victims; M:F = 330:115 (p < 0.001). Hangings accounted for the highest
      proportion of cases (107/445; 24%) followed by gunshot wounds (96/445; 21.6%),
      drug toxicity (82/435; 18.9%), drowning (66/445; 14.8%), and carbon monoxide
      toxicity (52/445; 11.7%). A miscellaneous group accounted for 42 of 445 cases
      (9.2%). No significant changes occurred in either the total suicide rate or in
      the rates in males and females, except for drowning deaths in males, which showed
      a significant decrease over time (p < 0.01). Female victims tended to avoid
      violent methods such as gunshot wounds in favour of drug overdose. Gunshot wound
      deaths were far less common than published data from other countries would
      indicate, with relative increases in deaths due to hanging, drug toxicity,
      drowning and carbon monoxide toxicity. An awareness of the considerable
      variability that occurs among populations in suicide methods and rates is
      important in determining local requirements for suicide prevention campaigns.

PMID- 15261002
TI  - A survey on the involvement of accident and emergency doctors in medicolegal work
      in Hong Kong.
AB  - This study reports the results from a questionnaire survey on the pattern of
      medico-legal work undertaken by doctors working in Accident & Emergency
      Departments (ED) and their self-evaluation of competency in forensic medicine. A
      total of 155 questionnaires were returned with a response rate of 46%. Only 30%
      (46) respondents were fellows of the Hong Kong College of Emergency Medicine but
      46% (71) had more than 6 years of experience working in the ED. Most of the
      requests for medical report came from police and insurance companies. Fellows had
      more experience writing reports on homicide, sexual assault and child abuse than
      non-fellows did. Nearly all fellows and three quarters (74%) of non-fellows had
      given evidence in courts of law. Physical assault was the commonest and sexual
      assault the least common experience. Most respondents had experience of attending
      district court (83%), followed by coroner inquest (67%), magistracy (66%) and
      high court (45%). Respondents were asked to rate themselves on their competence
      in various subject areas. It can be seen that respondents were less comfortable
      in areas like homicide, child abuse and sexual assault. On the job coaching by a
      senior seems to be the major mode of training. Both fellows (61%) and non-fellows
      (36%) favored some form of courses with a hands-on workshop element in future.

PMID- 15261003
TI  - Penile lesions -- reinforcing the case against suspects of sexual assault.
AB  - In most cases of sexual assault, even following long term abuse, genital and
      extra-genital injuries may be very scarce or literally not found. Though the
      forensic experts customary illustrate to the court that the absence of physical
      trauma does not rule out that the assault had taken place, more substantial
      medical evidence can be helpful in pursuing a conviction. We present three cases
      examined in the National Center of Forensic Medicine in Tel-Aviv in which
      information obtained during questioning of the victims concerning genital
      pathology of the assailant was later verified through examination of the
      suspects. Such data may provide key evidence to get an indictment when the
      assault is perpetrated by a stranger or a person who should not have an intimate
      relationship with the victim. Therefore, acquiring information from the victim
      concerning any pathology of the assailant's genitalia should be part of the
      routine questionnaire form of victims of suspected sexual assault or abuse as
      findings of this sort may become paramount in conviction of perpetrators.

PMID- 15261004
TI  - Sexual arousal and orgasm in subjects who experience forced or non-consensual
      sexual stimulation -- a review.
AB  - The review examines whether unsolicited or non-consensual sexual stimulation of
      either females or males can lead to unwanted sexual arousal or even to orgasm.
      The conclusion is that such scenarios can occur and that the induction of arousal
      and orgasm does not indicate that the subjects consented to the stimulation. A
      perpetrator's defence simply built upon the fact that evidence of genital arousal
      or orgasm proves consent has no intrinsic validity and should be disregarded.

PMID- 15261005
TI  - Poisoning deaths in married women.
AB  - Unnatural deaths of married women amongst the total female deaths have been an
      increasing trend in Indian society during the recent past years. These unnatural
      deaths may be suicide, homicide or even accidents. But these suicides and
      homicides are currently more commonly associated with the dowry disputes. In
      India, dowries are a continuing series of gifts endowed before and after the
      marriage. When dowry expectations are not met, the young bride may be killed or
      compelled to commit suicide, either by burning, poisoning or by some other means.
      Here, in the study, the main objective is to present the different
      epidemiological and medicolegal aspects of poisoning deaths in the married women.
      In a cohort of 200 married female deaths, 35 (18%) were poisoning deaths and
      these were analyzed from both epidemiological and medicolegal aspects. In this
      series, most of the women consumed organophosphorus compound and died within 10
      days. The majority of the affected wives due to dowry problems were below 35
      years of age. Most incidents occurred either during morning hour or during
      daytime.

PMID- 15261006
TI  - Pre-hospital and hospital traumatic deaths in the former homeland of Transkei,
      South Africa.
AB  - This retrospective descriptive study on 274 medicolegal cases was to determine
      the issues related to pre-hospital and hospital deaths in injured patients and to
      determine whether any of the deaths were preventable in the area. Interviews of
      the family members were conducted individually before carrying out autopsies.
      Time of survival after trauma, place of death, and the cause of death were
      recorded along with the demographic information -- age, sex, occupation, and
      personal habits. Umtata General Hospital in the Eastern Cape Province is the
      referral hospital for a surrounding population of about 400,000. Seventy four
      percent (74%) of the victims had been declared, 'presumably dead' at the scene by
      the community or police, and taken to mortuary without any death certification by
      a physician. The rest (26%) were taken to hospital where later they succumbed to
      trauma. Out of these only 4% underwent surgery. The majority (68%) of the victims
      were young ( < 40 years). The causes of deaths were: motor vehicle accidents
      (MVA) 32%, gunshot 24%, stab injury 17%, blunt trauma 9% and miscellaneous (fall
      from height, burns, etc.) 17%. Head and chest injuries were the commonest 50%.
      Only 17% survived from days to weeks. About 75% subjects died within 6 h of the
      trauma. There is a very high pre-hospital (74%) mortality of trauma patients in
      the Transkei region. The fact that members of the community or police and not a
      medical practitioner confirmed deaths raises the ethical issue of right to life.
      Some may actually be alive when they are considered dead. As it appears that 12%
      of pre-hospital deaths are preventable, employing more medical personnel in the
      rural areas along with an effective ambulance service would seem to be required.

PMID- 15261007
TI  - Flying under the influence of alcohol.
AB  - A case of a man arrested for being in charge of an aircraft under the influence
      of alcohol is described. He received a Formal Caution and his pilots licence
      suspended indefinitely. The law and regulations about airplane flying and alcohol
      is discussed.

PMID- 15261008
TI  - Suicide by buflomedil HCl: a case report.
AB  - A man was found dead in his bed by his relatives; a half-empty wrapping of Loftyl
      Plus (the trade name of a vasodilator medications containing buflomedil HCl
      marketed in Italy) was on the bedside table. GC/MS analysis of a blood sample
      collected during the autopsy revealed a buflomedil HCl concentration
      approximately of about 20 times the therapeutic values.

PMID- 15261009
TI  - Synthesis and CMC studies of 1-methyl-3-(pentafluorophenyl)imidazolium quaternary
      salts.
AB  - Critical Micelle Concentration (CMC) of sodium dodecyl sulfate (SDS), an anionic
      surfactant, has been investigated in 30 mM aqueous solutions of 1-benzyl-3
      methylimidazolium chloride (1) and 1-methyl-3-(pentafluorophenyl)imidazolium
      chloride (2). The CMC of SDS is significantly lower in the presence of 2 as
      compared to that of 1. The decreased CMC of SDS in the presence of 2 is in
      accordance with its increased hydrophobicity due to the fluorinated side chain.
      The thermogravimetric analysis of compounds 1 and 2 shows that they are thermally
      stable up to about 290 degrees C.

PMID- 15261010
TI  - Adhesion of Pseudomonas fluorescens on magnetic surfaces.
AB  - The adhesion of Pseudomonas fluorescens (ATCC 700830) to perpendicularly
      polarized magnetic surfaces was recently discovered. The findings have found that
      the magnetic free surfaces from different magnetic polarities have different
      profound effects on the P. fluorescens bacterial adhesion to its surfaces. These
      phenomena can be explained by the surface magnetic effect, which was found to
      affect the surface free energy. An in situ experiment, by contrast microscopy and
      under static conditions, was conducted to determine the influence of magnetic
      surfaces, that are polarized under different external magnetizing field
      strengths, on bacterial adhesion. The effect of different magnetic polarities on
      the surface free energy has also been investigated.

PMID- 15261011
TI  - Bacterial adhesion to glass and metal-oxide surfaces.
AB  - Metal oxides can increase the adhesion of negatively-charged bacteria to surfaces
      primarily due to their positive charge. However, the hydrophobicity of a metal
      oxide surface can also increase adhesion of bacteria. In order to understand the
      relative contribution of charge and hydrophobicity to bacterial adhesion, we
      measured the adhesion of 8 strains of bacteria, under conditions of low and high
      ionic strength (1 and 100 mM, respectively) to 11 different surfaces and examined
      adhesion as a function of charge, hydrophobicity (water contact angle) and
      surface energy. Inorganic surfaces included three uncoated glass surfaces and
      eight metal-oxide thin films prepared on the upper (non-tin-exposed) side of
      float glass by chemical vapor deposition. The Gram-negative bacteria differed in
      lengths of lipopolysaccharides on their outer surface (three Escherichia coli
      strains), the amounts of exopolysaccharides (two Pseudomonas aeruginosa strains),
      and their known relative adhesion to sand grains (two Burkholderia cepacia
      strains). One Gram positive bacterium was also used that had a lower adhesion to
      glass than these other bacteria (Bacillus subtilis). For all eight bacteria,
      there was a consistent increase in adhesion between with the type of inorganic
      surface in the order: float glass exposed to tin (coded here as Si-Sn), glass
      microscope slide (Si-m), uncoated air-side float glass surface (Si-a), followed
      by thin films of (Co(1-y-z)Fe(y)Cr(z))3O4, Ti/Fe/O, TiO2, SnO2, SnO2:F, SnO2:Sb,
      A1(2)O3, and Fe2O3 (the colon indicates metal doping, a slash indicates that the
      metal is a major component, while the dash is used to distinguish surfaces).
      Increasing the ionic strength from 1 to 100 mM increased adhesion by a factor of
      2.0 +/- 0.6 (73% of the sample results were within the 95% CI) showing
      electrostatic charge was important in adhesion. However, adhesion was not
      significantly correlated with bacterial charge and contact angle. Adhesion (A) of
      the eight strains was significantly (P < 10(-25)) correlated with total adhesion
      free energy (U) between the bacteria and surface (A = 2162e(-1.8U)). Although the
      correlation was significant, agreement between the model and data was poor for
      the low energy surfaces (R2 = 0.68), indicating that better models or additional
      methods to characterize bacteria and surfaces are still needed to more accurately
      describe initial bacterial adhesion to inorganic surfaces.

PMID- 15261012
TI  - Microbially induced flotation and flocculation of pyrite and sphalerite.
AB  - Cells of Paenibacillus polymyxa and their metabolite products were successfully
      utilized to achieve selective separation of sphalerite from pyrite, through
      microbially induced flocculation and flotation. Adsorption studies and
      electrokinetic investigations were carried out to understand the changes in the
      surface chemistry of bacterial cells and the minerals after mutual interaction.
      Possible mechanisms in microbially induced flotation and flocculation are
      outlined.

PMID- 15261013
TI  - Effect of ultrasound stimulation on metabolic modulation of pyruvic acid.
AB  - Pyruvic acid lay on the center position of Eremothecium ashbyii metabolic fluxes,
      during fermentation, a high performance liquid chromatography (HPLC) method is
      presented for the simultaneous determination of pyruvic acid in the Eremothecium
      ashbyii cell culture of both with ultrasound stimulation and the control. Dry
      weight and riboflavin are also mentored. The results of this study show that the
      ultrasound stimulation can give rise to pyruvic acid change, at the same time;
      change of pyruvic acid concentration is correlative to that of dry weight of
      mycelium and content of riboflavin.

PMID- 15261014
TI  - A new experimental design for screening Chinese medicine formula.
AB  - In this paper, an appropriate scale screening for traditional Chinese medicine
      formula was developed in according to verified pharmacological experiments with
      uniform optimized experimental design and orthogonal optimized experimental
      design. Meanwhile, a most appropriate match of prescription dosage for curing
      vascular disease was got, which was based on NO value of pharmacodynamics
      experimental data and the endothelial cells configuration which would changed in
      a degree when damaged by hydration diamine. The appropriate scale of the formula
      was Ginkgo extraction: substance A:B:C = 100:20:50:0.01. This formula was more
      optimized and effective than other formula compared by pharmacological and
      validated experiments.

PMID- 15261015
TI  - Extraction of total RNA from Chrysanthemum containing high levels of phenolic and
      carbohydrates.
AB  - Some standard methods are available in total RNA extraction of plant tissue,
      which are effective for the ordinary plants. But it is difficult to extract the
      total RNA from the plants with high levels of phenolic compounds, carbohydrates,
      or other compounds that bind and/or coprecipitate with RNA. In this paper, a
      method was described that used the soluble polyvinylpyrrolidone (PVP), ethanol
      precipitation, phenol extraction and LiCl precipitation. By this method, RNA
      capable of reverse-transcription and polymerase chain reaction (PCR)
      amplification was isolated from Chrysanthemum that contains high levels of
      phenolic compounds and carbohydrates. The OD260/OD280 absorbance ratio is 2, and
      the RNA is intact. Other specialized RNA extraction methods failed to deliver
      suitable product. Bands of PCR products are clearly appearing on the
      polypropylene acyl gel electrophoresis (PAGE) gel, which indicates that the
      purity, concentration and integrity of total RNA were suitable for the sequent
      researches.

PMID- 15261016
TI  - Effect of 1.7 MHz ultrasound on a gas-vacuolate cyanobacterium and a gas-vacuole
      negative cyanobacterium.
AB  - Ultrasonic signals propagated through medium were directly applied to unicellular
      cyanobacterium cell surfaces to investigate the biological effects induced by
      ultrasound. The gas-vacuolate cyanobacterium Microcystis aeruginosa and the gas
      vacuole negative cyanobacterium Synechococcus PCC 7942 responded differently to
      ultrasound. When M. aeruginosa was irradiated by 1.7 MHz ultrasound at 0.6 W cm(
      2) every day, it showed a decrease of nearly 65% in biomass increment, and this
      group's generation time increased twice as much as the control. While
      Synechococcus culture irradiated every day still grew as fast as the control, and
      its final biomass was as much as the control. The value of the electric
      conductivity change (Deltasigma) sharply increased in Microcystis suspension
      during the exposure process, which revealed more ultrasonic cavitation yield in
      liquid related to the gas-vacuolate cyanobacteria. The relative malondialdehyde
      (MDA) content, a quantitative indicator of lipid peroxidation, increased by 65%
      in Microcystis cells and 9% in Synechoccus cells after ultrasonic irradiation.
      Moreover, the membrane permeability, quantified by measuring the relative amount
      of electrolyte leaking out of cells, increased to more than 60% in the
      Microcystis cells. The results indicated that Microcystis cells were susceptible
      to ultrasonic stress. According to Rayleigh-Plesset's bubble activation theory,
      1.7 MHz ultrasound approached the eigenfrequency of gas-vacuolate cells. The
      present investigation suggested the importance of the cavitational effect
      relative to intracellular gas-vacuoles in the loss of cell viability. In summary,
      1.7 MHz ultrasonic irradiation was effective in preventing water-bloom forming
      cyanobacteria from growing rapidly due to changes in the functioning and
      integrity of cellular and subcellular structures.

PMID- 15261017
TI  - Biocompatibility and biostability of a series of poly(carbonate)urethanes.
AB  - In this work, we synthesized several MDI-based poly(carbonate)urethanes (PCU) by
      using four different soft segments, including two aliphatic macrodiols
      (poly(hexyl, ethyl)carbonate diols, MW 2017 and 865, respectively) and two
      aromatic macrodiols (MW approximately 2000 and 1000, respectively), in different
      molar ratios to MDI. We demonstrate that these polymers exhibited various degree
      of micro-phase separation that further influenced their surface protein
      adsorption, platelet activation as well as cellular attachment and growth.
      Polyurethanes based on poly(hexyl, ethyl)carbonate diol with MW 2017 in a molar
      ratio MDI/macrodiol/chain extender of either 3/2/1 or 4/3/1 resulted in greater
      micro-phase separation as well as superior biocompatibility and biostability.

PMID- 15261018
TI  - Study of the diclofenac/phospholipid interactions with liposomes and monolayers.
AB  - The interaction of diclofenac sodium (SD) with soya phosphatidylcholine (SPC) has
      been studied with floating Langmuir monolayers and liposomes. SD was either
      introduced into the subphase of SPC monolayers or co-spread with SPC on an
      aqueous subphase. In both cases, SD caused the surface pressure isotherm to
      become more expanded, thus demonstrating the affinity between SD and SPC. The
      incorporation of SD caused SPC liposomes to have a decreased diameter according
      to light scattering experiments. When SPC liposomes were injected into an aqueous
      subphase, their destruction yielding surface-active monomers could be monitored
      by changes in surface pressure. SD-loaded liposomes displayed a much faster
      kinetics when the surface density of surface-active monomers was plotted against
      time, with rate constants increasing significantly with the SD concentration. The
      kinetic profile can be quantitatively analyzed by plotting ln[1 - (gamma/gamma
      infinity)] versus t1/2.

PMID- 15261019
TI  - Platelet adhesive resistance of polyurethane surface grafted with zwitterions of
      sulfobetaine.
AB  - A possible approach to improve the blood compatibility of poly(etherurethane)s
      (PU) involves the covalent attachment of key molecular on its surface. Recently,
      polymer tailed with zwitterions was found having good blood compatibility. The
      purpose of present study was to design and synthesis a novel nonthrombogenic
      biomaterial by modifying the surface of poly(etherurethane) with zwitterions of
      sulfobetaine via HDI spacer. The films of polyurethane were grafted with
      sulfobetaine by a three-step procedure. In the first step, the film surfaces were
      treated with hexamethylene diisocyanate (HDI) in toluene at 50 degrees C in the
      presence of di-n-butyl tin dilaurate(DBTDL) as a catalyst. The extent of the
      reaction was measured by ATR-IR spectra; a maximum number of free NCO group was
      obtained after a reaction time of 2.5 h. In the second step, the primary amine
      group of N,N-diethylethylenediamine (DEA) or N,N-dimethylethylenediamine (DMA)
      was allowed to react in toluene with isocyanate groups bound on surface. In the
      third step, two kinds of sulfobetaines were formed in the surface through the
      ring-opening reaction between tertiary amine of DMA or DEA and 1,3-
      propanesultone (PS). The reaction process was monitored with ATR-IR spectra and
      XPS spectra. The wettability of films was investigated by water contact angle
      measurement. A platelet adhesion experiment was conducted as a preliminary test
      to confirm the improved blood compatibility of PU. The number of platelets
      adhering to PU decreased greatly compared to original after 1 h and 3 h of
      contact with human plate-rich plasma.

PMID- 15261020
TI  - Blood compatibility of polyurethane surface grafted copolymerization with
      sulfobetaine monomer.
AB  - Surface modification is an effective way to improve the hemocompatibility and
      remain bulk properties of biomaterials. Recently, polymer tailed with zwitterions
      was found having good blood compatibility. In this study, the grafting
      copolymerization of sulfobetaine onto polyurethane surface was obtained through
      two steps. In the first step, polyurethane film coupled with vinyl groups was
      obtained through the reaction between the carboxyl group of acrylic acid (AA) and
      the NH-urethane group of polyurethane by dicyclohexylcarbodiimide (DCC). In the
      second step, sulfobetaine was grafted copolymerization on the surface using AIBN
      as an initiator. The reaction process was monitored with ATR-IR spectra and X-ray
      photoelectron spectroscopy (XPS) spectra. The wettability of films was
      investigated by water contact angle measurement. The blood compatibility of the
      grafted films was evaluated by platelet adhesion in platelet rich plasma (PRP)
      and protein absorption in bovine fibrinogen (BFG). Low platelet adhesion was
      observed on the grafted films incubated in PRP for 1 and 3 h, respectively. The
      protein absorption was reduced on the grafted films after incubated in bovine
      fibrinogen for 2 h. All of these results revealed that the improved blood
      compatibility was obtained by grafting copolymerization with zwitterionic monomer
      of sulfobetaine onto polyurethane film. In addition, introducing vinyl groups
      onto surface through DCC and AA is a novel method to functionalize polyurethane
      for further modification.

PMID- 15261021
TI  - Efficient intracellular delivery of rifampicin to alveolar macrophages using
      rifampicin-loaded PLGA microspheres: effects of molecular weight and composition
      of PLGA on release of rifampicin.
AB  - Monodispersed PLGA microspheres containing rifampicin (RFP) have been prepared by
      solvent evaporation method using a Shirasu porous glass (SPG) membrane. The
      microspheres were spherical and their average diameter was about 2 microm. The
      loading efficiency of rifampicin was dependent on the molecular weight of PLGA.
      The higher loading efficiency was obtained by the usage of PLGA with the lower
      molecular weight, which may be caused by the interaction of the amino groups of
      rifampicin with the terminal carboxyl groups of PLGA. PLGA with the monomer
      compositions of 50/50 and 75/25, of lactic acid/glycolic acid, were used in this
      study. From rifampicin-loaded PLGA microspheres formulated using PLGA with the
      molecular weight of 20,000, rifampicin was released with almost constant rate for
      20 days after the lag phase was observed for the initial 7 days at pH 7.4. On the
      other hand, from rifampicin-loaded PLGA microspheres formulated using PLGA with
      the molecular weight of 5000 or 10,000, almost 90% of rifampicin-loaded in the
      microspheres was released in the initial 10 days. Highly effective delivery of
      rifampicin to alveolar macrophages was observed by the usage of rifampicin-loaded
      PLGA microspheres. Almost 19 times higher concentration of rifampicin was found
      to be incorporated in alveolar macrophages when rifampicin-loaded PLGA
      microspheres were added to the cell culture medium than when rifampicin solution
      was added.

PMID- 15261022
TI  - Correlation between structure and transfection efficiency: a study of DC-Chol-
      DOPE/DNA complexes.
AB  - The supramolecular structural nature of some cationic liposomes-DNA complexes,
      currently used as vehicles in non-viral gene delivery, has been elucidated by
      recent X-ray diffraction experiments. The relationship between the chemico
      physical properties of these self-assembled structures and their transfection
      efficiency is extensively studied. Here we report a first comprehensive
      structural study by using energy dispersive X-ray diffraction, of the complex DC
      Chol--DOPE/DNA (3beta[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol
      dioleoylphosphatidylethanolamine/DNA), which has been classified as one of the
      most effective in in-vivo experiments. Our results show that DC-Chol--DOPE/DNA
      lipoplexes have a columnar inverted hexagonal structure, which is not influenced
      by the cationic liposome/DNA charge ratio. The transfection efficiency of C6 rat
      glioma cells by DC-Chol--DOPE/DNA lipoplexes and the toxicity of lipoplexes to
      cells are dramatically affected by cationic liposome/DNA weight ratio. It seems
      therefore that the lipoplex structures have not any influence on transfection
      efficiency and toxicity in our experimental system.

PMID- 15261023
TI  - The influence of polyelectrolyte charges of polyurethane membrane surface on the
      growth of human endothelial cells.
AB  - A novel technique to introduce free amino groups onto polyester scaffolds via
      aminolyzing the ester groups with diamine has been developed recently. The
      introduction of the free amino groups on these polyester surfaces provides us the
      possibility to modify polymer surface in a simpler manner, e.g. layer-by-layer
      assembly of charged species. By this technique, many negatively and positively
      charged biopolymers were deposited alternatively on polyurethane surface. The
      deposition process was monitored by fluorescence spectroscopy and advancing
      contact angle measurements. The result of human endothelial cells cultured in
      vitro showed that cells on negatively charged surface could not spread and
      flatten well due to the electrostatic repulsion. The lower attachment ratio
      induced the lower proliferation ratio. However, after the surface charge was
      inversed by collagen, both attachment and proliferation ratios increased to
      different extent. Observed under SEM, cells also presented a flat and spreading
      morphology.

PMID- 15261024
TI  - Surface shear rheology of WPI-monoglyceride mixed films spread at the air-water
      interface.
AB  - Surface shear viscosity of food emulsifiers may contribute appreciably to the
      long-term stability of food dispersions (emulsions and foams). In this work we
      have analyzed the structural, topographical, and shear characteristics of a whey
      protein isolate (WPI) and monoglyceride (monopalmitin and monoolein) mixed films
      spread on the air-water interface at pH 7 and at 20 degrees C. The surface shear
      viscosity (etas) depend on the surface pressure and on the composition of the
      mixed film. The surface shear viscosity varies greatly with the surface pressure.
      In general, the greater the surface pressure, the greater are the values of etas.
      The values of etas for the mixed WPI-monoolein monolayer were more than one order
      of magnitude lower than those for a WPI-monopalmitin mixed film, especially at
      the higher surface pressures. At higher surface pressures, collapsed WPI residues
      may be displaced from the interface by monoglyceride molecules with important
      repercussions on the shear characteristics of the mixed films. A shear-induced
      change in the topography and a segregation between domains of the film forming
      components were also observed. The displacement of the WPI by the monoglycerides
      is facilitates under shear conditions, especially for WPI-monoolein mixed films.

PMID- 15261025
TI  - Effects of surfactants on foliar uptake of herbicides - a complex scenario.
AB  - Surfactants are almost always present in herbicide treatment solutions with the
      aim to improve spray droplet retention on and penetration of active ingredients
      (a.i.s) into plant foliage. The effects of surfactants on the foliar uptake of
      herbicides are complex and only partially understood. The influence of a range of
      non-ionic polyoxyethylene surfactants on the uptake of two herbicides, glyphosate
      and 2,4-dichlorophenoxyacetic acid (2,4-D), was compared using three plant
      species, wheat, broad bean and common lambsquarters. Surfactants of higher
      ethylene oxide (EO) content provided greater uptake enhancement for glyphosate,
      whereas those of lower EO content were more beneficial for 2,4-D uptake. Among
      surfactants of the same EO content, those containing a C(13)/C(15) linear alkane
      hydrophobe moiety appeared to be more efficient for promoting the uptake of both
      herbicides. When a suitable surfactant was used, glyphosate uptake into both bean
      and wheat foliage increased steadily with increasing surfactant concentration and
      reached a maximum at 0.5%. In the presence of a constant surfactant, higher
      percentage uptake of herbicide was obtained with higher a.i. concentrations for
      glyphosate, but with lower a.i. concentrations in the case of 2,4-D. In the
      presence of an organosilicone surfactant, the stomatal uptake of glyphosate
      varied with both surfactant concentration and plant species. The effect of non
      silicone surfactants on the cuticular uptake of glyphosate also varied with plant
      species. It can be concluded that the effects of surfactants on foliar uptake of
      herbicides depend not only on their chemical structures (hydrophobe and
      hydrophile moieties) and concentration, but also on the physicochemical
      properties and concentration of a.i.s and the leaf surface character of the plant
      species.

PMID- 15261026
TI  - Relationship between the minute structure and the lodging resistance of rice
      stems.
AB  - The aim of this experiment is to measure the morphological and mechanical
      properties, and to analyze the relationship between the morphology and lodging
      resistance of several different kinds of rice stem. Choose the typical species of
      tall, mid and short stem and hybrid rice, ten individual plants each species (all
      should be caulis), and when paddies are full heading, intercept the third
      internode above the ground. The minute structure characteristics include the size
      of outer diameter, Culm wall thickness, and the number of big and small vascular
      bundles. Mechanical properties include the tensile breaking point and the tensile
      elastic modulus. Based on the above characteristics it is concluded that the
      middle stem has the highest lodging resistance. Thus when we select the high
      yield and lodging resistance species, the middle and rigid stem should be
      considered.

PMID- 15261027
TI  - A dynamic wicking technique for determining the effective pore radius of
      pregelatinized starch sheets.
AB  - A dynamic wicking technique is employed for the first time for the determination
      of the effective mean pore radius of a thin-layer porous food: drum dried
      pregelatinized starch sheets. The technique consists of measuring the penetration
      rate of various n-alkanes in the porous matrix of the starch sheets and using
      this data to calculate the effective pore radius via the Washburn equation. Pore
      sizes in the order of a few nanometers have been determined in the starch sheets
      depending on the drum dryer's operating variables (drum rotation speed, steam
      pressure and starch feed concentration). The conditions for the application of
      the technique in porous foods are discussed as compared to the conditions for
      single capillaries and inorganic porous material measured in other studies.

PMID- 15261028
TI  - Adsorption and desorption of lysozyme on nano-sized magnetic particles and its
      conformational changes.
AB  - Adsorption and desorption of lysozyme on nano-sized magnetic particles and its
      conformational change were studied in this work. Adsorption of lysozyme on nano
      sized magnetic particles (Fe(3)O(4)) was carried out at different pH. Maximum
      adsorption of lysozyme (4.65 mg/m2) occurred at its isoelectric point (pI =
      11.1). Differential scanning calorimetry (DSC) results show that the lysozyme
      adsorbed on magnetic particles did not show any thermal transition over the range
      20-100 degrees C. High desorption of lysozyme from magnetic particles was
      achieved using NaH(2)PO(4) (pH 4.0) (90%) and NaSCN (pH 6.0) (97%) as desorbents.
      The conformational change of the lysozyme desorbed by NaH(2)PO(4) was small,
      while the lysozyme desorbed by NaSCN underwent a significant conformational
      change as measured by the intrinsic fluorescence. Eighty-eight and 82% activity
      was retained in the desorbed enzyme for desorption by NaH(2)PO(4) and NaSCN,
      respectively.

PMID- 15261029
TI  - Complex formation in aqueous medium of partially hydrolysed oat cereal proteins
      with sodium stearoyl-2 lactylate (SSL) lipid surfactant and implications for bile
      acids activity.
AB  - Sodium stearoyl-2 lactylate (SSL) lipid surfactant molecules specifically bind
      partially hydrolysed oat proteins in aqueous medium and significantly enhance the
      dispersion stability of oat cereal preparations. The proposed complexation is
      composition dependent and a greater understanding of the role of both oat
      proteins and lipid surfactant in the effect was gained with data from high
      performance liquid chromatography (HPLC-UV), viscometry and differential scanning
      micro calorimetry. The effect of the lipid surfactant on the degree of
      association is primarily governed by the conformational activity of oat protein
      molecules related to the extent of protein hydrolysed state, as well as protein
      unfolded and subsequent aggregated structures. SSL does not dissociate oat
      proteins into subunits or destroy important hydrophobic contacts already
      stabilising the protein molecules. Although the exact mode of association is
      unknown, the present study demonstrates that such interactions occur in a
      specific manner and suggest selectivity of oat proteins for individual fatty
      acids. The effect of various amounts of bile acids on SSL-oat protein interaction
      was also investigated, as a first attempt to investigate the role of lipid
      surfactant molecules in the known cholesterol-lowering action of oat cereal
      ingredients and to elucidate favourable conditions by which oat cereal can elicit
      hypocholesterolemic effects.

PMID- 15261030
TI  - Characterization of dehydration behavior of untreated and pulverized creatine
      monohydrate powders.
AB  - Creatine, which is well known as an important substance for muscular activity, is
      synthesized from amino acids such as glycine, arginine and ornithine in liver and
      kidney. It then accumulates in skeletal muscle as creatine phosphoric acid. The
      aim of this study was to understand the dehydration behavior of untreated and
      pulverized creatine monohydrate at various temperatures. The removal of crystal
      water was investigated by using differential scanning calorimetry (DSC), X-ray
      powder diffraction and scanning electron microscopy (SEM). The X-ray diffraction
      pattern of untreated and pulverized creatine monohydrate agreed with reported
      data for creatine monohydrate. However, the diffraction peaks of the (100), (200)
      and (300) planes of pulverized creatine monohydrate were much stronger than those
      of untreated creatine monohydrate. On the other hand, the diffraction peaks of
      the (012) and (013) planes of untreated creatine monohydrate were much stronger
      than those of pulverized creatine monohydrate. The dehydration of untreated and
      pulverized creatine monohydrate was investigated at various storage temperatures,
      and the results indicated that untreated and pulverized creatine monohydrate were
      transformed into the anhydrate at more than 30 degrees C. After dehydration, the
      particles of untreated and pulverized creatine anhydrate had many cracks. The
      dehydration kinetics of untreated and pulverized creatine monohydrate were
      analyzed by the Hancock-Sharp equation on the basis of the isothermal DSC data.
      The dehydrations of untreated and pulverized creatine monohydrate both followed a
      zero-order mechanism (Polany-Winger equation). However, the transition rate
      constant, calculated from the slope of the straight line, was about 2.2-7.7 times
      higher for pulverized creatine monohydrate than for untreated creatine
      monohydrate. The Arrhenius plots (natural logarithm of the dehydration rate
      constant versus the reciprocal of absolute temperature) of the isothermal DSC
      data for untreated and pulverized creatine monohydrate were linear. The
      activation energies of dehydration in the 40-60 degrees C range for untreated and
      pulverized creatine monohydrate were 15.02 and 10.1 kJ/mol, respectively.
      Dehydration of untreated creatine monohydrate had a pronounced effect on the
      particle size of the powder. Compared with pulverized creatine monohydrate, the
      particle size of untreated creatine monohydrate was significantly decreased by
      dehydration.

PMID- 15261031
TI  - Surface properties of bamboo fiber and a comparison with cotton linter fibers.
AB  - In order to understand the different touch senses from bamboo and cotton fibers,
      the surface properties of bamboo fiber, e.g., the surface free energy, the
      Lifshitz-van der Waals force, and Lewis acid and base components have been
      determined using the column wicking technique. Taking the traditional cotton
      linter fiber as a reference, this paper shows that both these fibers have the
      similar surface free energies. However, a big difference between these two fibers
      which has been importantly observed is that the bamboo fiber having greater Lewis
      acid component seems to be double than the cotton linter fiber. Since water has
      been found to have such surface property, it is suggested that the bamboo fiber
      touch in the skin of people may like the touch between water and skin of people.
      Meanwhile, other surface properties of these two fibers are compared.

PMID- 15261032
TI  - FT-IRRAS spectroscopic studies of the interaction of avidin with biotinylated
      dendrimer surfaces.
AB  - The interaction of avidin with biotin on a functional Au surface containing
      fourth generation amine-terminated polyamidoamine (G4-NH(2) PAMAM) dendrimers was
      investigated through the use of Fourier transform infrared reflection-adsorption
      spectroscopy (FT-IRRAS). The first step in the fabrication of the functional
      surfaces used was the construction of an aldehyde-terminated self-assembled
      monolayer (SAM) through the treatment of Au-coated glass slides with ethanol
      solutions of self-synthesized 2-hydroxypentamethylene sulfide (HPMS). The as
      formed aldehyde-terminated monolayer was subsequently immersed in methanol
      solutions of G4-NH(2) PAMAM dendrimer to obtain well-organized primary amine
      terminated surfaces. Biotinylation of the amine-terminated layers thus obtained
      was accomplished by use of the N-succinimidyl ester of biotin. Each step of the
      synthetic process, as well as the performance of final surface for protein
      recognition was monitored by FT-IRRAS. In particular, the molecular recognition
      ability was examined and quantified by use of an alkyne dicobalt hexacarbonyl
      probe coupled with avidin. Non-specific adsorption of avidin was determined by
      exposure of the amine-terminated and/or biotinylated surfaces to solutions of
      biotin-saturated avidin. The results indicate that the biotinylated G4-NH(2)
      PAMAM dendrimer layers formed according to this procedure have a high capacity
      for binding avidin with relatively high specificity. The performance of these
      layers (i.e. both binding capacity and specificity) improve substantially when 6
      mercapto-1-hexanol (MH) is present as a co-adsorbent during the formation of the
      initial aldehyde-terminated layers. This effect can be attributed to the dilution
      of the initial aldehyde-terminated SAM, leading to a more favorable spatial
      arrangement of the subsequent biotinylated surfaces.

PMID- 15261033
TI  - Investigation on the effects of diamide on NO production in vascular endothelial
      cells (VEC).
AB  - Nitric oxide (NO) controls several physiological functions of the cardiovascular
      system. The study on the effect of diamide (N(2)H(4).H(2)O) on NO production in
      vascular endothelial cells (VEC) may provide significant reference for VEC's
      modeling in studying cardiovascular diseases. The objective of this study was to
      elucidate how high concentration diamide (V(diamide)/V(culture miedium) = 5 ml/l)
      and low concentration diamide (V(diamide)/V(culture miedium) = 0.5 ml/l) affect
      NO production in a human endothelial cell line (ECV304). After cells were
      incubated with diamide (5 or 0.5 ml/l) for 4, 6, 8 or 10h, respectively, the
      amounts of NO metabolites released by the cells were quantitated and the degree
      of damage of VEC was observed using microscope. The results showed that NO
      production in VEC tended to decrease with the lapse of time in the 0.5 ml/l
      diamide group. In the 5 ml/l diamide group, on the contrary, NO production in VEC
      tended to increase with the lapse of time. At the same time, from the morphologic
      observation, the VEC were damaged severely after treated with 5 ml/l diamide. So
      it could be concluded that the severe damage induced by high concentration
      diamide would have triggered the express of inducible nitric oxide synthases
      (iNOS). Just for the expresssion of iNOS, NO production in VEC treated with high
      concentration diamide occurred abnormally in contrast to the 0.5 ml/l group.

PMID- 15261034
TI  - Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer
      coated microbubbles.
AB  - Langmuir trough methods and fluorescence microscopy were combined to investigate
      the phase behavior and microstructure of monolayer shells coating micron-scale
      bubbles (microbubbles) typically used in biomedical applications. The monolayer
      shell consisted of a homologous series of saturated acyl chain phospholipids and
      an emulsifier containing a single hydrophobic stearate chain and polyethylene
      glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase
      lipids and phase separated from condensed phase lipids. Phase coexistence was
      observed in the form of dark condensed phase lipid domains surrounded by a sea of
      bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area
      fractions and domain morphologies, including networks and other novel structures,
      were observed in each batch of microbubbles. Network domains were reproduced in
      Langmuir monolayers under conditions of heating-cooling followed by compression
      expansion, as well as in microbubble shells that underwent surface flow with
      slight compression. Domain size decreased with increased cooling rate through the
      phase transition temperature, and domain branching increased with lipid acyl
      chain length at high cooling rates. Squeeze-out of the emulsifier at a surface
      pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and
      directly visualized with fluorescence microscopy, although collapse of the solid
      lipid domains occurred at much higher surface pressures. Compression of the
      monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark
      shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier
      was reincorporated upon subsequent expansion. Factors that affect shell formation
      and evolution, as well as implications for the rational design of microbubbles in
      medical applications, are discussed.

PMID- 15261035
TI  - Effect of electrolytes on the surface behavior of rhamnolipids R1 and R2.
AB  - The surface behavior of solutions of the rhamnolipids, R1 and R2, were
      investigated in the absence and presence of an electrolyte (NaCl) through surface
      tension measurements and optical microscopy at pH 6.8. The NaCl concentrations
      studied are 0.05, 0.5 and 1M. Electrolytes directly affect the carboxylate groups
      of the rhamnolipids. The solution/air interface has a net negative charge due to
      the dissociated carboxylate ions at pH 6.8 with strong repulsive electrostatic
      forces between the rhamnolipid molecules. This negative charge is shielded by the
      Na(+) ions in the electrical double layer in the presence of NaCl, causing the
      formation of a close-packed monolayer, and a decrease in CMC, and surface tension
      values. The maximum compaction is observed at 0.5M NaCl concentrations for R1 and
      R2 monolayers, with the R1 monolayer more compact than R2. The larger spaces left
      below the hydrophobic tails of R1 with respect to that of R2, due to the missing
      second rhamnosyl groups are thought to be responsible for the higher compaction.
      The rigidity of both R1 and R2 monolayers increases with the electrolyte
      concentration. The rigidity of the R1 monolayer is greater than that of R2 at all
      NaCl concentrations due to the lower hydrophilic character of R1. The variation
      of CMC values as a function of NaCl concentration obtained from the surface
      tension measurements and critical packing parameter (CPP) calculations show that
      spherical micelles, bilayer and rod like micelles are formed in the rhamnolipid
      solutions as a function of the NaCl concentration. The results of optical
      microscopy supported these aggregation states indicating lamellar nematic liquid
      crystal, cubic lamellar and hexagonal liquid crystal phases in R1 and R2
      solutions depending on the NaCl concentration.

PMID- 15261036
TI  - A synthetic alternative to natural lecithins with antimicrobial properties.
AB  - Two soft biocompatible cationic surfactants from the amino acid arginine, 1,2
      dilauroyl-3-acetylarginyl-rac-glycerol (1212RAc) and 1,2-dimirystoyl-3
      acetylarginyl-rac-glycerol (1414RAc), were prepared. Their physicochemical
      properties show that they can be classified as multifunctional surfactants with
      self-aggregation behaviour comparable to that of short-chain lecithins. The two
      surfactants can simultaneously stabilise water-in-oil (W/O) droplets and oil-in
      water (O/W) droplets, forming multiple emulsions. They have antimicrobial
      activity similar to that of conventional cationic surfactants and are as harmless
      as amphoteric betaines. These surfactants constitute an interesting alternative
      to the diglycerides and lecithins in formulations that require antimicrobial
      properties.

PMID- 15261037
TI  - Role of surface activity in the biological actions of ranitidine and famotidine.
AB  - The role of surface activity has been studied in the biological actions of
      ranitidine (RNT) and famotidine (FMT). The drugs have been shown to generate
      liquid membranes in series with a supporting membrane with the virtue of their
      amphiphilicity. Transport of histamine, acetylcholine, and ions (chloride,
      bicarbonate, potassium, sodium and calcium) have been studied in the presence of
      liquid membranes generated by surface-active RNT and FMT. The data on the
      modifications in the permeability of histamine, acetylcholine and ions indicate
      that the liquid membranes generated by RNT and FMT may play a significant role in
      their biological action. The surface-active nature of the drugs has been
      discussed with relevance to their pharmacological effects.

PMID- 15261038
TI  - A study of molecular complex formation between propyl gallate and ascorbic acid
      in the microemulsion phase of sodium dodecyl sulfate, pentanol and water system.
AB  - The association between two water-soluble antioxidants, i.e. ascorbic acid and
      propyl gallate have been studied by absorption spectroscopy in microemulsion
      formed in sodium dodecyl sulfate/pentanol/water micellar system. It has been
      shown that propyl gallate forms 1:1 molecular complex with ascorbic acid in every
      solution. Evolution of the absorption spectra during the study of molecular
      complex formation goes through well-defined isosbestic points. The association
      constants were calculated using curve-fitting procedure. The observed
      interactions are stronger in the less polar solvents.

PMID- 15261039
TI  - Dehydration of solute-lipid systems: hydration forces analysis.
AB  - Sorption isotherms were obtained for a range of lipid/sugar/water mixtures. These
      were analysed using a simple hydration forces formalism. The results demonstrate
      that this simple analysis can be used to estimate dehydration parameters for
      these relatively complex systems. This in turn provides some insight into the
      location and role of sugars in the hydration behaviour of lipid systems. The
      relevance of these results to the phase behaviour of lipid/sugar mixtures during
      dehydration are discussed.

PMID- 15261040
TI  - Synthesis and micellar characterization of short block length methoxy
      poly(ethylene glycol)-block-poly(caprolactone) diblock copolymers.
AB  - A series of short block length methoxy poly(ethylene glycol)-block
      poly(caprolactone) diblock copolymers was synthesized and characterized in order
      to assess the potential of these copolymers as a micellar drug-delivery system.
      Varying the caprolactone:MePEG weight ratio in the reaction mixture allowed the
      synthesis of diblock copolymers with a MePEG molecular weight of 750 g/mol and
      PCL block lengths of 2, 5 or 10 repeat units. Phase diagrams of aqueous solutions
      of the copolymers were constructed which displayed characteristic cloud points
      and Krafft points. As the degree of polymerization of PCL increased, critical
      micelle concentration (CMC) values decreased from 6.97 x 10(-1) to 3.38 x 10(-3)
      g/l, partition equilibrium coefficients (Kv) increased from 1.09 x 10(4) to 22.2
      x 10(4),and hydrodynamic diameters increased from 12.2 to 19.5 nm. The micelle
      morphology was determined to be spherical by transmission electron microscopy.

PMID- 15261041
TI  - The effect of cetyltrimethyl ammonium bromide on the electrochemical
      determination of thyroxine.
AB  - Electrochemical behavior of thyroxine at a polyvinylpyrrolidone modified carbon
      paste electrode in the presence of cetyltrimethyl ammonium bromide was described.
      Thyroxine underwent totally irreversible oxidation at this system and a well
      defined peak at 0.42 V was obtained. The influence of various surfactants on the
      oxidation of thyroxine was examined by cyclic voltammetry. Chronocoulometry was
      also used to investigate the electrode process. In the range 2 x 10(-7) to 9 x
      10(-6)mol/l, the thyroxine concentration was linear with the oxidation peak
      current and a low detection limit of 8 x 10(-8) mol/l was obtained for 5 min
      accumulation.

PMID- 15261042
TI  - Adsorption of a phospholipid-hydroperoxide glutathione peroxidase into
      phospholipid monolayers at the air-water interface.
AB  - The interfacial behavior differences of two glutathione peroxidase isoforms have
      been investigated. The first isoform is the phospholipid-hydroperoxide
      glutathione peroxidase (EC 1.11.1.12) (GPx-4) isolated from rat testes and the
      second one is the cytosolic glutathione peroxidase (EC 1.11.1.9) (GPx-1) from
      bovine erythrocytes. Injected in the subphase buffer of a Langmuir trough, GPx-4
      was able to adsorb quickly at the air-water interface whereas the GPx-1 was not.
      Then, the protein interaction with phospholipid monolayers was explored. Indeed,
      a monolayer of phospholipids containing a different number of polyunsaturated
      fatty acyl chains was prepared at the air-water interface. Under each kind of
      monolayer, the protein solution was injected and its adsorption was visualized by
      the measurement of successive pressure-area isotherms. We have, then, determined
      the molecular area increase due to the protein adsorption. It was found that the
      GPx-4 is adsorbed in each kind of monolayer tested whereas no molecular area
      increase was detected with the GPx-1. This indicates that the GPx-4 has a higher
      affinity for the interface, recovered or not by lipids, than the GPx-1. Moreover,
      the GPx-4 presents a different affinity for the phospholipid monolayers depending
      on the number of polyunsaturated fatty acyl chains.

PMID- 15261043
TI  - Glycolipid based cubic nanoparticles: preparation and structural aspects.
AB  - Kinetically stable cubic colloidal particle dispersion was produced from a
      glycolipid using a novel preparation strategy based on the dialysis principle.
      The use of synchrotron small-angle X-ray diffraction (SSAXD) permitted the
      identification of exact structure of these dispersed particles in the colloidal
      state. Dynamic light scattering methods were used to obtain size and size
      distributions. A glycoside, 1-O-phytanyl-beta-D-xyloside (beta-XP), that exhibits
      Pn3m cubic phase in an excess aqueous medium, was used as the lipid material. The
      dialysis technique includes controlled stirring action both inside and outside of
      the dialysis membrane tube. Initially, a mixed micellar system composed of beta
      XP, n-octyl-beta-D-glucopyranoside (beta-OG) and a triblock copolymer, Pluronic
      F127 (PL) was prepared in the aqueous medium. About 10 wt.% of PL to lipid weight
      was found to be sufficient to produce stable colloidal dispersions. The mean
      volume diameter of these colloidal particles was found to be in the range of 0.85
      +/-0.05 microm. The cubic phase structure of these colloidal particles is greatly
      depended on the final beta-OG concentration level in the system. Coexistence of
      Im3m and Pn3m cubic structures has been identified in these colloidal particles.
      This coexistence has the characteristics of Bonnet relation, which forms a
      compelling case for the infinite periodic minimal surface (IPMS) descriptions.
      These colloidal particles could restore pure Pn3m phase structure, but a longer
      dialysis time was needed. This work, in general, will open up new possibilities
      for membrane protein reconstitution and other relevant biological applications
      using colloidal cubic lipid particles.

PMID- 15261044
TI  - Ionic liquids as modulators of the critical micelle concentration of sodium
      dodecyl sulfate.
AB  - Critical micelle concentration (CMC) of sodium dodecyl sulfate (SDS), an anionic
      surfactant, has been investigated in aqueous solutions of a variety of room
      temperature ionic liquids (RTILs): 1,3-dimethylimidazolium iodide (Me2IM-I, 2), 1
      butyl-3-methylimidazolium chloride (BMIM-Cl, 3), 1-hexyl-3-methylimidazolium
      chloride (HxMIM-Cl, 4), 1-methyl-3-octylimidazolium chloride (MOIM-Cl), 5, and 1
      methyl-3-octylimidazolium tetrafluoroborate (MOIM-BF4, 6). The CMC of SDS is
      shown to correlate with the nature of the alkyl groups in the RTILs; SDS showed
      appreciably higher CMCs in presence of ionic liquids 2 and 3, whereas in the
      presence of ionic liquids 4, 5, and 6 much smaller CMCs were observed. The nature
      of the gigenions, Cl- or BF4-, has no noticeable effect on the observed CMC
      values.

PMID- 15261045
TI  - Atomic force microscopy study of cellulose surface interaction controlled by
      cellulose binding domains.
AB  - Colloidal probe microscopy has been used to study the interaction between model
      cellulose surfaces and the role of cellulose binding domain (CBD), peptides
      specifically binding to cellulose, in interfacial interaction of cellulose
      surfaces modified with CBDs. The interaction between pure cellulose surfaces in
      aqueous electrolyte solution is dominated by double layer repulsive forces with
      the range and magnitude of the net force dependent on electrolyte concentration.
      AFM imaging reveals agglomeration of CBD adsorbed on cellulose surface. Despite
      an increase in surface charge owing to CBD binding to cellulose surface, force
      profiles are less repulsive for interactions involving, at least, one modified
      surface. Such changes are attributed to irregularity of the topography of protein
      surface and non-uniform distribution of surface charges on the surface of
      modified cellulose. Binding double CBD hybrid protein to cellulose surfaces
      causes adhesive forces at retraction, whereas separation curves obtained with
      cellulose modified with single CBD show small adhesion only at high ionic
      strength. This is possibly caused by the formation of the cross-links between
      cellulose surfaces in the case of double CBD.

PMID- 15261046
TI  - Photophysical properties of pyrene in interaction with the surface of melanin
      particles.
AB  - Melanins perform their biological activity (photoprotection and light enhanced
      chemical reactivity) under the form of porous aggregates on which ions and
      neutral molecules can be adsorbed. For this reason, the photochemistry of natural
      and synthetic melanins must be investigated in the framework of the physico
      chemical theory of the heterogeneous reactions and a detailed knowledge of the
      surface properties, is therefore, necessary. In this work, some surface
      characteristics of melanin particles have been investigated taking advantage of
      the photophysical behaviour of pyrene, a dye widely used in studies of the
      interface properties of micelles and colloidal semiconductors. Our fluorescence
      study has allowed to obtain valuable informations regarding the micro
      environmental polarity of the melanin surface (that influences the vibronic
      structure of the emission spectra), the excimer formation, the lifetimes of the
      emissions and the kinetics of quenching by Cu2+.

PMID- 15261047
TI  - Impact of lipopolysaccharide coating on clay particle wettability.
AB  - Impact of lipopolysaccharide coating on kaolinite and Na-montmorillonite
      wettability was investigated. Kaolinite had greater diiodomethane contact angles,
      smaller water and formamide contact angles than Na-montmorillonite. After
      lipopolysaccharide coating, diiodomethane and formamide contact angles decreased,
      while water contact angles increased for both kaolinite and Na-montmorillonite.
      The decrease and increase in liquid contact angles after lipopolysaccharide
      coating were most pronounced for lipopolysaccharide extracted from Pseudomonas
      aeruginosa, followed by Pseudomonas fluorescens and Echerichia coli. Clay
      particle wettability was determined by particle surface thermodynamic properties.
      Both kaolinite and Na-montmorillonite exhibited a monopolar surface and the
      monopolarity decreased after lipopolysaccharide coating, indicating an increase
      in hydration or surface wetness. The origins of interactions of clay particles
      with water molecules were discussed and related to clay particle water
      wettability.

PMID- 15261048
TI  - Polyurethane vascular catheter surface grafted with zwitterionic sulfobetaine
      monomer activated by ozone.
AB  - Polyurethane (PU) is a conventional biomedical material with favorable
      biocompatibility and excellent mechanical properties and widely used in making
      vascular catheter, but its antithrombogenic property is not good enough to make
      it as a more demanding applicable biomaterial. Surface modification is an
      effective way to improve the hemocompatibility for biomaterials. The purpose of
      present study was to use ozonization method to modify the surface of PU vascular
      catheter slice to improve its antithrombogenicity by grafting N,N-dimethyl-N
      methacryloxyethyl-N-(3-sulfopropyl) ammonium (DMMSA), a zwitterionic sulfobetaine
      monomer. PU vascular catheter (PUVC) grafted with DMMSA (PUVC-g-PDMMSA) was
      characterized by ATR-FTIR and XPS. ATR-FTIR and XPS investigation confirmed the
      graft polymerization. The blood compatibility of the grafted films was evaluated
      by platelet rich plasma (PRP) platelet adhesion study and scanning electron
      microscopy (SEM) was used to observe the morphology of platelet using PU vascular
      catheter (PUVC) as the reference. No platelet adhesion was observed for the
      grafted PUVC slice incubated with PRP at 37 degrees C for 120 min. It is
      significant that this new zwitterionic sulfobetaine grafted PUVC have improved
      antithrobogenicity. It is effective that the inner surface of vascular catheter
      with inner diameter in only 3mm can be grafted with PDMMSA by using ozonization
      method.

PMID- 15261049
TI  - Interaction of flavonoids within organized molecular assemblies of anionic
      surfactant.
AB  - The interaction of various flavonoids (compounds having C6-C3-C6 configuration)
      with sodium dodecyl sulfate (SDS) an anionic surfactant was studied through
      absorption spectroscopy as a function of the concentration of surfactant above
      and below the critical micelle concentration (CMC) of the surfactant. A mechanism
      was proposed for the interaction between these flavonoids and anionic
      surfactants. The approximate number of additive molecules (flavonoids)
      incorporated per micelle was estimated at a particular concentration of SDS.
      Incorporation of additive in micelles shifts the UV absorption bands towards
      higher wavelengths of different magnitude. The spectral shift also depends upon
      the nature of the surfactant head group. The absorption spectra of the flavonoids
      in aqueous solution and in methanol are also reported.

PMID- 15261050
TI  - Associative phase separation of beta-lactoglobulin/pectin solutions: a kinetic
      study by small angle static light scattering.
AB  - Interpolymer complexation between beta-lactoglobulin (beta-lg) and pectin led to
      phase separation. Small angle static light scattering and phase contrast
      microscopy were used to monitor the phase separation of beta-lg/low-methoxyl or
      high-methoxyl-pectin (LM- or HM-pectin) dispersions as they were slowly acidified
      from pH 7 to 4 with glucono-delta-lactone (GDL). The monotonic decrease in
      scattered light intensity with the wave vector was associated with a nucleation
      and growth phase separation mechanism. Microscopic observations and turbidity
      measurements showed the increase of complex amounts with lower pH and at higher
      beta-lg/pectin ratios. The formation of intrapolymer complexes was initiated at
      pH 6.4 with the LM-pectin and at pH 5.0 with the HM-pectin. Local ordering with
      increasing amounts of small complexes was observed as scattered light intensity
      increased at intermediate q values. The beta-lg/LM-pectin complexes at the 5:1
      and the 2:1 weight ratios and the beta-lg/HM-pectin complexes at 5:1 weight ratio
      have fractal structures. The formation of large amounts of small assemblies and
      sedimentation would be responsible for the decrease in the number and volume mean
      diameters and fractal dimension of beta-lg/LM-pectin complexes over time.

PMID- 15261051
TI  - Calorimetric studies of the association of chitin and chitosan with sodium
      dodecyl sulfate.
AB  - The interaction of hydrophobic chitin and chitosan with sodium dodecyl sulfate
      (SDS) has been studied by titration calorimetry at 298.15K. The nature of
      interaction of the surfactant and biopolymers was followed by enthalpy
      interaction profiles. The mixing enthalpy curves were determined by mixing SDS
      solutions above their critical micelle concentration with chitin and chitosan
      suspensions in different concentrations. The Gibbs free energy of aggregation
      values were -23.21, -22.71 and -21.53 kJ mol(-1) for chitin in 0.02, 0.05 and
      0.1% concentration, respectively, and 28.30, 24.38 and 24.20 kJ mol(-1) for
      chitosan in 0.02, 0.05 and 0.1% concentration, respectively. The critical
      aggregation concentration (cac) obtained by calorimetric data gave 6.32, 7.07 and
      9.14 mmol kg(-1) in 0.02, 0.05 and 0.1% concentration, respectively, for chitin
      and 2.09, 4.91 and 5.11 mmol kg(-1) for chitosan in 0.02, 0.05 and 0.1%
      concentration, respectively.

PMID- 15261052
TI  - Systematic evolution of a porous hydroxyapatite-poly(vinylalcohol)-gelatin
      composite.
AB  - Hydroxyapatite (HAp)-poly(vinylalcohol) (PVA)-gelatin nanocomposite was
      biomimetically synthesized and characterized. Fourier transform infrared
      spectroscopy (FT-IR) analysis of hydroxyapatite, hydroxyapatite
      poly(vinylalcohol) and hydroxyapatite-poly(vinylalcohol)-gelatin composites show
      modification of hydroxyl, amide and phosphate bands as a result of chemical
      interaction of hydroxyapatite with the above composite matrices. Transmission
      electron microscopy (TEM) confirmed the time-dependent development of a porous
      structure of hydroxyapatite-poly(vinylalcohol)-gelatin as a consequence of
      nucleation at the HAp aggregate-matrix interface. A literature survey holds great
      promise for the above as scaffolds in terms of increased mechanical properties
      and bioactivity.

PMID- 15261053
TI  - Electrostatic interactions in protein adsorption probed by comparing lysozyme and
      succinylated lysozyme.
AB  - The influence of electrostatic interactions on protein adsorption was studied by
      comparing the adsorption of lysozyme and succinylated lysozyme at silica
      surfaces. The succinylation affects the charge of the protein, but also the
      stability. Although changes in stability can have an influence on adsorption, our
      data show that the primary effect can be entirely understood in terms of
      electrostatic interactions. The adsorbed amount as a function of pH has a maximum
      for both proteins. This maximum coincides with the isoelectric point for
      succinylated lysozyme, and is close to the isoelectric point for lysozyme. At pH
      values where the protein is electrostatically repelled by the sorbent, higher
      ionic strengths increase adsorption, and for electrostatic attraction higher
      ionic strengths decrease adsorption.

PMID- 15261054
TI  - Enhanced affinochromism of polydiacetylene monolayer in response to bacteria by
      incorporating CdS nano-crystallites.
AB  - By incorporating bio-specific receptors, such as p-10,12-pentacosadiyne-1-N
      (3,6,9-trioxaundecylamide)-alpha-D-mannopyranoside (MPDA), into 10,12
      pentacosadiyonic acid (PDA) monolayer, the MPDA/PDA monolayer underwent
      affinochromatic transition in response to the bacteria binding to the receptor.
      Here, we described a new method to study the membrane/macromolececular
      interaction between Escherichia coli (E. coli) and mannose and its relative
      affinochromism by modifying MPDA/PDA with CdS nano-crystallites (MPDA/PDA-CdS).
      CdS not only triggered the strong tropism of the bacteria but also reduced the
      rigidity of the MPDA/PDA backbone, resulting in the enhanced affinochromism. This
      discovery might be of significance in basic biophysical studies of
      membrane/macromolececular and designing novel biosensor.

PMID- 15261055
TI  - Adsorption of albumin and IgG to porous and smooth titanium.
AB  - The possibility to load submicrometer porous titanium surfaces with relatively
      small proteins, albumin and immunoglobulin G (IgG) was investigated. The loading
      ability is of interest due to the possibility of slow release of molecules from
      biomaterial surfaces, and may be important for the manipulation of wound healing
      around prostheses. Iodine-125 (125I) labeled albumin and IgG were adsorbed onto
      smooth and to porous titanium with a pore diameter of 200-300 nm. The smooth and
      porous surfaces were divided into three groups: hydrophilic, hydrophobic, or to
      amine-terminated silane (3-aminopropyltriethoxysilane) that bound proteins via
      glutaraldehyde. The protein solution pH and protein concentrations were varied,
      and the adsorption experiments made without or in the presence of calcium and
      magnesium ions. The adsorbed amounts were quantified with a gamma counter. Two to
      eleven times more proteins adsorbed onto porous than smooth surfaces and the
      adsorbed amounts increased with increasing protein concentration (0.1-10 mg/ml)
      during a constant incubation time. The elutability by sodium dodecyl sulphate
      (SDS) was incomplete on porous surfaces.

PMID- 15261056
TI  - Gelatine/silicate interactions: from nanoparticles to composite gels.
AB  - The possibility to design new composites associating biopolymers with mineral
      phases relies on the understanding and control of their mutual interactions. In
      this work, aqueous solutions of gelatine and sodium silicate were mixed at pH 5,
      37 degrees C and left to stand at 20 degrees C for 1 day. At low gelatine and
      high silicate contents, precipitates were obtained, containing a fixed
      silicon/polymer molar ratio. Scanning electron microscopy (SEM) reveals that they
      are formed of large aggregates of platelets, constituted of closely-packed
      nanoparticles. For high gelatine contents, composite gels were formed consisting
      of silica particles dispersed in the biopolymer matrix. Swelling studies indicate
      that the addition of silica decreases the stability of the gels by inducing
      gelatine depletion in solution. Similar experiments conducted at pH 7 show that
      at this pH, silicates are more effective at precipitating gelatine. A model is
      proposed for the formation of the composites, based on the electrostatic
      interactions arising between silicates and polymer chains. These results are
      discussed in the context of hybrid biomaterials design and biosilicification
      processes.

PMID- 15261057
TI  - Reaction of N-phenyl maleimide with aminosilane monolayers.
AB  - Reaction of N-phenyl maleimide (NPM) with silica surfaces modified with a self
      assembled monolayer of (aminopropyl)triethoxysilane (APTES) was investigated
      using infrared spectroscopy (FTIR), elemental analysis, and titration assays.
      This reaction is of interest as a test case for using amine-maleimide coupling
      for immobilization of biomolecules. Addition of NPM to surface APTES residues was
      consistently sub-stoichiometric, with typical yields of about 75% on monolayers
      with a coverage of 1.15 APTES residues/nm2. Titration analysis found negligible
      presence of imide alkene C=C bonds in modified supports, indicating that addition
      of NPM to APTES proceeded via amine attack at the imide olefinic bond. FTIR
      measurements also revealed presence of amide bands which intensified over periods
      of 10 h. These observations were attributed to a slower secondary process in
      which APTES amines attack imide carbonyls to produce amide linkages. Stability of
      NPM-modified surfaces was examined under room temperature storage in pH 7 buffer
      up to 72 h and for 2 h exposure to buffer at temperatures up to 90 degrees C. It
      was found that stability was determined by robustness of APTES-silica attachment,
      with about 30% loss under the harshest conditions investigated.

PMID- 15261058
TI  - BHK cells behaviour on laser treated polydimethylsiloxane surface.
AB  - The surface of polydimethylsiloxane (PDMS) was modified using a CO2-pulsed laser
      to evaluate the changes in physical and biological properties of the treated
      surface. Attachment of anchorage dependent cells, namely baby hamster kidney
      (BHK) fibroblastic cells, on PDMS surface was investigated in stationary culture
      conditions. BHK cell adhesion and growth on the PDMS surfaces were studied using
      scanning electron microscopy (SEM) and optical microscopy. To evaluate the
      surface wettability, water drop contact angles were determined. The laser treated
      PDMS surfaces showed high hydrophobicity and low cell adhesion, no spreading and
      growth in comparison with the unmodified PDMS. It was found that both the
      wettability and surface structure of the PDMS surface control cell attachment and
      growth.

PMID- 15261059
TI  - Correlated atomic force microscopy and fluorescence lifetime imaging of live
      bacterial cells.
AB  - We report on imaging living bacterial cells by using a correlated tapping-mode
      atomic force microscopy (AFM) and confocal fluorescence lifetime imaging
      microscopy (FLIM). For optimal imaging of Gram-negative Shewanella oneidensis MR
      1 cells, we explored different methods of bacterial sample preparation, such as
      spreading the cells on poly-L-lysine coated surfaces or agarose gel coated
      surfaces. We have found that the agarose gel containing 99% ammonium acetate
      buffer can provide sufficient local aqueous environment for single bacterial
      cells. Furthermore, the cell surface topography can be characterized by tapping
      mode in-air AFM imaging for the single bacterial cells that are partially
      embedded. Using in-air rather than under-water AFM imaging of the living cells
      significantly enhanced the contrast and signal-to-noise ratio of the AFM images.
      Near-field AFM-tip-enhanced fluorescence lifetime imaging (AFM-FLIM) holds high
      promise on obtaining fluorescence images beyond optical diffraction limited
      spatial resolution. We have previously demonstrated near-field AFM-FLIM imaging
      of polymer beads beyond diffraction limited spatial resolution. Here, as the
      first step of applying AFM-FLIM on imaging bacterial living cells, we
      demonstrated a correlated and consecutive AFM topographic imaging, fluorescence
      intensity imaging, and FLIM imaging of living bacterial cells to characterize
      cell polarity.

PMID- 15261060
TI  - UV-ozone modification of plasma-polymerised acetonitrile films for enhanced cell
      attachment.
AB  - Plasma polymerisation is of great interest for modifying the surface properties
      of biomedical devices in order to control, for example, protein adsorption and
      cell attachment. In this paper we present results for plasma-polymerised
      acetonitrile deposited onto silicon or polystyrene substrates. The chemistry of
      films deposited under a range of experimental conditions was studied by X-ray
      photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy
      (FTIR). XPS provided evidence that the elemental composition of the films varied
      with rf power to flow rate parameter (W/F) with films produced at higher W/F
      being deficient in nitrogen. FTIR revealed that the plasma deposited film
      contained a wide range of nitrogen functional groups including amine, imine and
      nitrile. Oxidation of the films by exposure to radiation from a low pressure
      mercury vapour lamp in an air ambient increased the surface oxygen levels from 3
      to 17at.% after 300 s exposure. XPS also revealed that the oxidation process
      proceeded via the formation of carbonyl groups at short exposure times (<60s)
      while longer treatment times (>60s) resulted in an increase in the concentration
      of carboxyl groups. To assess their potential to support cell growth, polystyrene
      culture dishes coated with plasma deposited films and UV-ozone oxidised films
      were seeded with 1BR.3.N human fibroblast cells and incubated for up to 72 h. Un
      oxidised plasma-polymerised acetonitrile films were found to give comparable cell
      attachment densities as tissue culture polystyrene. The greatest cell attachment
      density was found with plasma polymer films which had been UV-ozone treated for
      the longest time (300 s). Enhanced attachment to this surface was attributed to
      the high level of carboxylic groups found on this substrate.

PMID- 15261061
TI  - Cell-cell contact and membrane spreading in an ultrasound trap.
AB  - An ultrasonic standing wave trap [Langmuir 19 (2003) 3635] in which the
      morphologies of 2-D latex-microparticle aggregates, forming a pressure node
      plane, were characterised has been applied here to different cell suspensions
      with increasing order of specificity of cross-linking molecule, i.e. polylysine
      with chondrocytes; wheat germ agglutinin (WGA) with erythrocytes and surface
      receptors on neural cells. The outcome of initial cell-cell contact, i.e. whether
      the cells stuck at the point of contact (collision efficiency = 1) or rolled
      around each other (collision efficiency = 0), was monitored in situ by video
      microscopy. The perimeter fractal dimensions (FD) of 2-D hexagonally symmetric,
      closely packed aggregates of control erythrocytes and chondrocytes were 1.16 and
      1.18, respectively while those for the dendrititc aggregates formed initially by
      erythrocytes in 0.5microg/ml WGA and chondrocytes in 20 microg/ml polylysine were
      1.49 and 1.66. The FDs for control and molecularly cross-linked cells were
      typical of reaction-limited aggregation (RLA) and transport diffusion-limited
      aggregation (DLA), respectively. The FDs of the aggregates of cross-linked cells
      decreased with time to give more closely packed aggregates without clear
      hexagonal symmetry. Suspensions of neural cells formed dendritic aggregates.
      Spreading of inter-cellular membrane contact area occurred over 15 min for both
      erythrocyte and neural cell dendritic aggregates. The potential of the technique
      to characterise and control the progression of cell adhesion in suspension away
      from solid substrata is discussed.

PMID- 15261062
TI  - Characterization of hemoglobin immobilized on gamma-zirconium phosphate.
AB  - The fact that different gamma-zirconium phosphate (gamma-ZrP) preintercalation
      method induced varied degree and type of conformational change of the adsorption
      protein was confirmed by characterization techniques including circular dichroism
      (CD), fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction
      (XRD) analysis. The results indicated that the association of hemoglobin with
      gamma-ZrP preintercalated using butylamine was correlated with conformational
      change in the secondary structure of the protein. gamma-ZrP which was
      preintercalated with tetra (n-butylammonium) hydroxide caused the conformational
      change of Hemoglobin in both the secondary structure and the tertiary structure.
      X-ray powder diffraction analysis was used to analyze the crystalline structure
      of the nanocomposites prepared by relamination. The adsorption isotherms of
      Hemoglobin on different matrices were set up and fitted with Langmuir and
      Freundlich equations.

PMID- 15261063
TI  - Sintering behavior and apatite formation of diopside prepared by coprecipitation
      process.
AB  - Sintering behavior and bioactivity of diopside, CaMgSi(2)O(6), prepared by a
      coprecipitation process were examined for its biomedical applicability. As
      prepared powder was synthesized by adding aqueous ammonia to an ethanol solution
      containing Ca(NO(3))(2).4H(2)O, Mg(NO(3))(2).6H(2)O, and Si(OC(2)H(5))(4) and
      characterized by means of TG-DTA, XRD, and TG-MS. The dried powder was X-ray
      amorphous and crystallized into diopside at 845.5 degrees C. The glass network
      formation by SiO(4) tetrahedra was almost completed below 800 degrees C. The
      bioactivity of the diopside prepared by sintering the compressed powder at 1100
      degrees C for 2h was evaluated by immersion of the sintered body in a simulated
      body fluid (SBF) at 36.5 degrees C. Leaf-like apatite particles were found to be
      formed on the surface of the sintered body and grew with passage of soaking time.
      This apatite-forming behavior in the SBF is related to the dissolution of Ca(II)
      ions from the sintered body in the early stage of immersion. Thus, diopside
      prepared by the coprecipitation process using the metal alkoxide and the metal
      salts was found to have an apatite-forming ability.

PMID- 15261064
TI  - Expression of integrin beta1 and its roles on adhesion between different cell
      cycle hepatocellular carcinoma cells (SMMC-7721) and human umbilical vein
      endothelial cells.
AB  - To investigate expression of integrin beta1 and its roles on adhesion between
      different cell cycle hepatocellular carcinoma cell (HCC) and human umbilical vein
      endothelial cells (HUVEC), the synchronous G1 and S phase HCC were achieved
      through thymine-2-deoxyriboside and colchicines sequential blockage method and
      double thymine-2-deoxyriboside blockage method, respectively. Expression of
      integrin beta1 on hepatocellular carcinoma cells was detected with flow
      cytometer. Further, the adhesive force of HCC to HUVEC and the role of integrin
      beta1 in this adhesive course were studied by micropipette aspiration technique.
      The results showed that percentage of each cyclic phases of the controlled HCC
      (non-synchronous) are: G2 + M phase, 11%; G1 phase, 54%; S phase, 36%; the
      synchronous rates of G1 and S phase HCC amount to 74 and 98%, respectively. The
      expressive fluorescent intensity of integrin beta1 in G1 phase HCC is depressed
      significantly than the values of S phase and controlled HCC. Accordingly, the
      adhesive forces of G1 phase HCC to HUVEC was significantly lower than the value
      of S phase cells (P < 0.01), but it has no remarkable difference when compared
      the adhesive force values of S phase HCC with control; the contribution of
      integrin beta1 was about 50% in the adhesion of HCC to HUVEC. It suggested that
      HCC would be synchronized preferably in G1 and S phase with thymine-2
      deoxyriboside and colchicines, the adhesive molecule integrin beta1 expressed in
      a high lever in HCC and presented differences in vary cell cycle, and integrin
      beta1 played an important roles in adhesion of HCC to HUVEC. Possibly, S phase
      HCC take a great action in this adhesive course.

PMID- 15261065
TI  - Interaction of cubosomes with plasma components resulting in the destabilization
      of cubosomes in plasma.
AB  - Cubosomes are novel dispersed nanoparticles with bicontinuous cubic phases of
      monoolein in their interior. We investigated their disintegration process in
      plasma by in vitro and in vivo studies. Cubosomes were incubated with whole
      plasma or plasma components such as HDL, LDL, and albumin. The lypolysis study
      indicated lipolytic activity of whole plasma towards cubosomes. Gel filtration
      chromatography revealed that HDL, LDL and albumin interacted with cubosomes. HDL
      affected cubosomes' integrity and gave rise to smaller particles which contained
      the components of both cubosomes and HDL. Upon incubation with LDL, cubosomes
      fused with LDL. Albumin was shown to take up monoolein out of the particles.
      Cubosomes were disintegrated by whole plasma as a result of the interaction with
      plasma components. It was concluded that in vivo observation of a long
      circulation time of a hydrophobic substance in cubosomes was due to the sustained
      behavior of cubosome remnant particles.

PMID- 15261066
TI  - Adhesion of Cryptosporidium parvum and Giardia lamblia to solid surfaces: the
      role of surface charge and hydrophobicity.
AB  - Adhesion of Cryptosporidium parvum and Giardia lamblia to four materials of
      different surface charge and hydrophobicity was investigated. Glass beads were
      used with and without three polymer coatings: aminosilines (A0750), fluorosilines
      (T2494), an amino cationic polymer. Surface charge density and hydrophobicity of
      the beads were characterized by measuring the zeta potential (ZP) and the contact
      angle, respectively. Adhesion was derived from batch experiments where negatively
      charged (oo)cysts were mixed with the beads and recovery was determined by
      counting (oo)cysts remaining in suspension using a flow cytometer. Experimental
      results clearly show that adhesion to solid surfaces of C. parvum is different
      from G. lamblia. Adhesion of C. parvum to positively charged, hydrophilic beads
      (82% recovery relative to control) indicated that surface charge was the more
      important factor for C. parvum, dominating any hydrophobic effects. Adhesion of
      G. lamblia cysts to negatively charged, hydrophobic beads (0% recovery relative
      to control) indicated that although hydrophobicity and surface charge both played
      a role in the adhesion of G. lamblia to solid surfaces, hydrophobicity was more
      important than surface charge.

PMID- 15261067
TI  - Membrane properties of binary and ternary systems of ganglioside
      GM1/dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine.
AB  - The membrane properties of the ganglioside GM1 (GM1)/dioleoylphosphatidylcholine
      (DOPC) binary system and GM1/dipalmitoylphosphatidylcholine (DPPC)/DOPC ternary
      system were investigated using surface pressure measurements and atomic force
      microscopy (AFM), and the effect of surface pressure on the properties of the
      membranes was examined. Mixed GM1/DPPC/DOPC monolayers were deposited on mica
      using the Langmuir-Blodgett technique for AFM. GM1 and DOPC were immiscible and
      phase-separated. The AFM image of the GM1/DOPC (1:1) monolayer showed island-like
      GM1 domains embedded in the DOPC matrix. There was no morphological change on
      varying surface pressure. The surface pressure-area isotherm of the GM1/DPPC/DOPC
      (2:9:9) monolayer showed a two-step collapse as in the DPPC/DOPC (1:1) monolayer.
      The AFM image for the GM1/DPPC/DOPC monolayer showed DPPC and GM1 domains in the
      DOPC matrix, and the DPPC-rich phase containing GM1 showed a percolation pattern
      the same as the GM1/DPPC (1:9) monolayer. The percolation pattern in the
      GM1/DPPC/DOPC monolayer changed as the surface pressure was varied. The surface
      pressure-responsive change in morphology of GM1 was affected by the surrounding
      environment, suggesting that the GM1 localized in each organ has a specific role.

PMID- 15261068
TI  - Solution properties of amitriptyline and its partitioning into lipid bilayers.
AB  - Solution properties of a drug and its partitioning into lipid bilayers were
      studied for drug extraction using several different techniques, such as surface
      tension, zeta potential, ultra filtration and UV-Vis spectroscopy. From the
      surface tension study it was found that the presence of salt makes the drug
      molecules more surface-active. Zeta potential revealed the adsorption of the drug
      into the liposome bilayers to be governed mostly by electrostatic forces. The
      drug retention volume was expressed as a capacity factor, K, and that was
      normalized with respect to the amount of the immobilized phospholipids. The K
      values for the positively charged drug on the liposomes decreased in the presence
      of phosphate buffer due to the presence of the oppositely charged ions. The above
      methods can thus be used to understand the mechanism of drug-membrane interaction
      and quantification of drug absorption into liposomes.

PMID- 15261069
TI  - Effects of gemini surfactants on egg phosphatidylcholine bilayers in the fluid
      lamellar phase.
AB  - The influence of 1,4-butanediamonium-N,N'-dialkyl-N,N,N',N'-tetramethyl
      dibromides (CmA, m = 7-16 is the number of alkyl carbons) on the egg yolk
      phosphatidylcholine (EYPC) bilayer thickness and lipid surface area at the
      bilayer-aqueous phase interface is studied using X-ray diffraction on fluid
      lamellar CmA + EYPC + H2O phases as a function of CmA:EYPC and H2O:EYPC molar
      ratios and the alkyl chain length m. At the constant CmA:EYPC = 0.4 and H2O:EYPC
      = 18 molar ratios, the CmA induced bilayer thickness decrease shows a minimum and
      the lipid surface area increase a maximum at the alkyl chain length m = 9. The
      obtained results are discussed in the context of a structural perturbation model
      of the cut-off effect in biological potencies of surfactants which occurs when
      increasing the alkyl substituent chain length above the critical value.

PMID- 15261070
TI  - Surface attachment of nanoparticles using oligonucleotides.
AB  - Colloidal polymer particles are widely used in a variety of applications ranging
      from chromatography to surface modified bioreactors in protein arrays. In the
      present study, surface attachment of polystyrene particles to a polystyrene
      substrate has been performed using oligonucleotide hybridization. Thiolated
      complementary oligomers of cytosine and guanine have been covalently coupled to a
      pyridyl disulphide (PDS) modified polyethyleneglycol tether, forming part of a
      triblock copolymer which is adsorbed to the polystyrene surfaces via hydrophobic
      polypropylene oxide center blocks. The ability to withstand shear forces was
      studied using a laminar flow cell and the uptake of oligomers on the particles
      was quantified using two complementary techniques: UV-spectroscopy and
      sedimentation field flow fractionation. The possibility to tether particles in a
      flow cell suitable for practical use in e.g. a FIA-system is demonstrated.

PMID- 15261071
TI  - Silicon surface modification with a mixed silanes layer to immobilize proteins
      for biosensor with imaging ellipsometry.
AB  - One kind of surface modification method on silicon wafer was presented in this
      paper. A mixed silanes layer was used to modify silicon surface and rendered the
      surface medium hydrophobic. The mixed silanes layer contained two kinds of
      compounds, aminopropyltriethoxysilane (APTES) and methyltriethoxysilane (MTES). A
      few of APTES molecules in the layer was used to immobilize covalently human
      immunoglobulin G (IgG) on the silicon surface. The human IgG molecules
      immobilized covalently on the modified surface could retain their structures well
      and bind more antibody molecules than that on silicon surface modified with only
      APTES. This kind of surface modification method effectively improved the
      sensitivity of the biosensor with imaging ellipsometry.

PMID- 15261072
TI  - Polymerized ion pair amphiphile vesicles with pH-sensitive transformation and
      controlled release property.
AB  - Ion pair amphiphiles (IPA) composed of one proton-deionizable single or double
      alkyl chain ammonium surfactant and one anionic carboxylate surfactant with
      polymerizable dithiolane ring are prepared to develop polymerized microcapsules
      that can recognize pH change and transform itself under basic condition, thus
      releasing encapsulated materials at the desired point. Combination of pH
      sensitivity and polymeric solid structure, if fully developed, endows the IPA
      vesicle with smart function that is highly valuable in drug delivery application.
      Reasons for such high pH-sensitive vesicle transformation are sought from
      combined physical properties such as turbidity, zeta potential, surface tension,
      and release rate of marker through the vesicle membrane.

PMID- 15261073
TI  - Fabrication of alternating polycation and albumin multilayer coating onto
      stainless steel by electrostatic layer-by-layer adsorption.
AB  - Multilayer films consisting of polyethylenimine (PEI) and albumin were
      successfully prepared on biomedical 316L stainless steel surface via
      electrostatic self-assembly of the PEI and albumin. The process of electrostatic
      self-assembly of PEI/albumin was monitored by125I radiolabeling, electrochemical
      impedance spectroscopy (EIS) and atomic force microscopy (AFM). The EIS data
      revealed that the multilayer coating was stable in Tris-HCl (pH 7.35) buffer
      solution for 21 days. 125I radiolabeling experiments indicated that less than 10%
      albumin was eluted by PBS in 45 days. Static platelet adhesion experiments
      indicated that the PEI/albumin deposited on stainless steel could resist platelet
      adhesion effectively. Such an easy processing and shape-independent method may
      have good potential for surface modification of cardiovascular devices.

PMID- 15261074
TI  - Well-ordered self-assembled monolayer surfaces can be used to enhance the growth
      of protein crystals.
AB  - A series of hydrophobic self-assembled monolayers (SAMs) was generated by the
      adsorption of undecanethiol, dodecanethiol, and octadecanethiol onto transparent
      gold-coated glass microscope slides. Protein crystallization trials using
      droplets deposited on the surfaces of the optically transparent SAMs were
      compared to those for which the droplets were deposited on the surfaces of
      conventional silanized glass microscope slides. For the five distinct proteins
      examined in the crystallization trials (i.e., lysozyme, alpha-lactalbumin,
      hemoglobin, thaumatin, and catalase), the SAMs generally afforded, (1) a faster
      rate of crystallization, (2) a larger crystal size; and (3) a broader range of
      crystallization conditions than that afforded by silanized glass. The greatest
      enhancements were observed with the highly ordered SAMs derived from
      octadecanethiol, which are evaluated here for the first time.

PMID- 15261075
TI  - Surface pressure dependence of phospholipase A2 activity in lipid monolayers is
      linked to interfacial water activity.
AB  - The specific activity of pancreatic phospholipase A2 (PLA2) was studied in two
      disparate systems, one involving phosphatidylcholine monolayer at various surface
      pressures at the air-water interface and the other involving a solid-state system
      exposed to various equilibrium relative humidity (ERH). The results were examined
      in terms of thermodynamic activity of water in the interfacial region (aws*) and
      in the hydrated solid phase (aw). In both these physically different systems, the
      specific activity versus aw and aws* profiles of PLA2 were remarkably similar. In
      both cases, the specific activity exhibited a maximum at aw (or aws*)
      approximately 0.3. These results suggested that the mechanism of control of PLA2
      activity at the lipid-water interface might involve modulation of the hydration
      state of the enzyme through control of the thermodynamic activity of water in the
      interfacial region. Extension of these results to biomembranes suggests that one
      of the functions of lipid bilayer might be the control of local water activity at
      the lipid-water interface. In biological membranes, localized subtle changes in
      interfacial water activity may occur as a result of local stretching or
      compression of the membrane facilitated by conformational changes in membrane
      bound receptor proteins.

PMID- 15261076
TI  - Phase behavior of DOPE/TritonX100 (reduced) in dilute aqueous solution: aggregate
      structure and pH-dependence.
AB  - The phase behavior of dilute mixtures of dioleoylphosphatidylethanolamine (DOPE)
      and reduced TritonX100 (TX100(r)) has been investigated at pH 7.4 and 10. Using
      simple turbidity measurements and optical observations, together with cryo
      transmission electron microscopy (cryo-TEM), we estimate the phase boundaries. We
      show that at both pH 7.4 and 10, a very large amount of surfactant is needed for
      the onset of micelle formation (X(TX100(r)) approximately 0.60-0.70) as well as
      for a complete solubilization of DOPE into mixed micelles (X(TX100(r)) > 0.94).
      We find that the micelles that are formed at high TX100(r) concentrations are of
      spherical shape. Increasing the pH from 7.4 to 10 has a comparably small effect
      on the transition from a lamellar (Lalpha) to a micellar (L1) phase. However, the
      reversed hexagonal phase (H(II)) that is present at low surfactant content at pH
      7.4 is absent at pH 10. This is due to the partial negative charge of DOPE at pH
      10. We determine the fraction of charged DOPE (alpha = 0.34) at pH 10 in a 150 mM
      NaCl buffer using zeta-potential (zeta-potential) measurements in combination
      with a Poisson-Boltzmann (PB) model. The intrinsic pK(a) of the primary amino
      group of DOPE, in a pure DOPE membrane, is estimated to 9.15 +/- 0.2.

PMID- 15261077
TI  - Surface activity of thymol: implications for an eventual pharmacological
      activity.
AB  - In the present work, we studied the ability of thymol to affect the organization
      of model membranes and the activity of an intrinsic membrane protein, the GABA(A)
      receptor (GABA(A)-R). In this last aspect, we tried to elucidate if the action
      mechanism of this terpene at the molecular level, involves its binding to the
      receptor protein, changes in the organization of the receptor molecular
      environment, or both. The self-aggregation of thymol in water with a critical
      micellar concentration approximately = 4 microM and its ability to penetrate in
      monomolecular layers of soybean phosphatidylcholine (sPC) at the air-water
      interface, even at surface pressures above the equilibrium, lateral pressure of
      natural bilayers were demonstrated. Thymol affected the self-aggregation of
      Triton X-100 and the topology of sPC vesicles. It also increased the polarity of
      the membrane environment sensed by the electrochromic dye merocyanine. A dipolar
      moment of 1.341 Debye was calculated from its energy-minimized structure. Its
      effect on the binding of [3H]-flunitrazepam ([3H]-FNZ) to chick brain
      synaptosomal membranes changed qualitatively from a tendency to the inhibition to
      a clear activatory regime, up on changing the phase state of the terpene (from a
      monomeric to a self-aggregated state). Above its CMC, thymol increased the
      affinity of the binding of [3H]-FNZ (K(d-control)= 2.9, K(d-thymol)= 1.7 nM)
      without changing the receptor density (B(max-control)= 910, B(max-thymol)= 895
      fmol/mg protein). The activatory effect of thymol on the binding of [ [3H]-FNZ
      was observed even in the presence of the allosteric activator gamma-aminobutyric
      acid (GABA) at a concentration of maximal activity, and was blocked by the GABA
      antagonist bicuculline. Changes in the dipolar arrangement and in the molecular
      packing of GABA(A)-R environment are discussed as possible mediators of the
      action mechanism of thymol.

PMID- 15261078
TI  - The adsorption of human serum albumin (HSA) on CO2 laser modified magnesia
      partially stabilised zirconia (MgO-PSZ).
AB  - Magnesia partially stabilised zirconia (MgO-PSZ), a bioinert ceramic, exhibits
      high mechanical strength, excellent corrosion resistance and good
      biocompatibility, but it does not naturally form a direct bond with bone
      resulting in a lack of osteointegration. The surface properties and structure of
      a biomaterial play an essential role in protein adsorption. As such, changes in
      the surface properties and structure of biomaterials may in turn alter their
      bioactivity. So, the fundamental reactions at the interface of biomaterials and
      tissue should influence their integration and bone-bonding properties. To this
      end, CO2 laser radiation was used to modify the surface roughness, crystal size,
      phase and surface energy of the MgO-PSZ. The basic mechanisms active in improving
      the surface energy were analysed and found to be the phase change and augmented
      surface area. The adsorption of human serum albumin (HSA), which is a non-cell
      adhesive protein, was compared on the untreated and CO2 laser modified MgO-PSZ.
      It was observed that the thickness of the adsorbed HSA decreased as the polar
      surface energy of the MgO-PSZ increased, indicating that HSA adsorbed more
      effectively on the hydrophobic MgO-PSZ surface than the hydrophilic surface. The
      current study provided important information regarding protein-biomaterial
      interactions and possible mechanisms behind the cell interaction and in vivo
      behaviour.

PMID- 15261079
TI  - Interactions between hematological derivatives and dipalmitoyl phosphatidyl
      choline: implications for adult respiratory distress syndrome.
AB  - Blood and its components flood the alveoli in adult respiratory distress syndrome
      (ARDS) and may be responsible for the inhibition of lung surfactant in this
      syndrome. We have evaluated the surface properties of dipalmitoyl
      phosphatidylcholine (DPPC) monolayers-the main component of lung surfactant, in
      the presence of blood and its components. Experiments were performed using a
      Langmuir-Blodgett trough at physiological temperature (37 degrees C), pH 7.0 and
      using 0.9% saline as the sub-phase. Whole blood (WB), membranes obtained from
      whole blood cells (Mem), lysed blood (LB), homogenized blood clot (CLOT), serum
      (SER), platelet rich plasma (PRP), platelet poor plasma (PPP) and individual
      plasma proteins (albumin, fibrinogen) were added to the sub-phase in the
      equivalent proportion of 10 parts of DPPC per million parts (w/v) of
      hematological inhibitor. Cell membranes were found to be the most inhibitory
      agent for DPPC surface activity as evidenced by an increase in the minimum
      surface tension (from 0.818 +/- 0.219 to 7.373 +/- 0.854 mN/m) and percentage
      area change required to reduce the surface tension from 30 to 10 mN/m (from 21.24
      +/- 0.99 to 66.83 +/- 4.44). The inhibitory potential of pure plasma proteins
      differed from those of more complex blood derivatives like platelet rich plasma
      and serum. Whole blood and platelet poor plasma were non-inhibitory, but serum,
      platelet rich plasma and clot significantly increased the minimum surface tension
      of DPPC to 6.819 +/- 0.925, 6.625 +/- 2.261 and 6.060 +/- 0.640 mN/m,
      respectively. These results were statistically significant with one-way analysis
      of variance and Newman-Keul's test (P < 0.05). The present study suggests that,
      not only the presence of the individual blood component(s) in the lung alveoli
      but also their interactions decide their inhibitory capability. Pure plasma
      proteins are not representative of the inhibitory effects of blood derivatives
      like serum, platelet rich plasma and blood cell membranes which would be more
      relevant for inhibitory models of ARDS.

PMID- 15261080
TI  - Biosorption of nickel(II) and copper(II) ions from aqueous solution by
      Streptomyces coelicolor A3(2).
AB  - The biosorption of nickel(II) and copper(II) ions from aqueous solution by dried
      Streptomyces coelicolor A3(2) was studied as a function of concentration, pH and
      temperature. The optimum pH range for nickel and copper uptake was 8.0 and 5.0,
      respectively. At the optimal conditions, metal ion uptake was increased as the
      initial metal ion concentration increased up to 250 mg l(-1). At 250 mg l(-1)
      copper(II) ion uptake was 21.8% whereas nickel(II) ion uptake was found to be as
      high as 7.3% compared to those reported earlier in the literature. Metal ion
      uptake experiments were carried out at different temperatures where the best ion
      uptake was found to be at 25 degrees C. The characteristics of the adsorption
      process were investigated using Scatchard analysis at 25 degrees C. Scatchard
      analysis of the equilibrium binding data for metal ions on S. coelicolor A3(2)
      gave rise to a linear plot, indicating that the Langmuir model could be applied.
      However, for nickel(II) ion, divergence from the Scatchard plot was evident,
      consistent with the participation of secondary equilibrium effects in the
      adsorption process. Adsorption behaviour of nickel(II) and copper(II) ions on the
      S. coelicolor A3(2) can be expressed by both the Langmuir and Freundlich
      isotherms. The adsorption data with respect to both metals provide an excellent
      fit to the Freundlich isotherm. However, when the Langmuir isotherm model was
      applied to these data, a good fit was obtained for the copper adsorption only and
      not for nickel(II) ion.

PMID- 15261081
TI  - Effect of pH and ionic strength on competitive protein adsorption to air/water
      interfaces in aqueous foams made with mixed milk proteins.
AB  - Quantitative analysis of competitive milk protein adsorption to air/water
      interfaces in aqueous foam was performed by capillary electrophoresis (CE). Foams
      were made by whipping protein solutions, in which skim milk powder (SMP) and whey
      protein isolate (WPI) were mixed at 0.5% protein in different proportions at
      different pH values and NaCl concentrations. Preferential adsorption of beta
      casein into foam phases occurred under most solution conditions, if partial
      dissociation of the casein micelles had occurred. Preferential adsorption of beta
      casein was not observed with added Ca2+, due to the re-association of casein
      micelles. Enrichment of caseins into the foam phase was more apparent than that
      of whey proteins. The foamability of SMP demonstrated a continuous improvement
      due to the gradually increasing dissociation of casein micelles when the
      concentration of NaCl increased from 0 to 0.8 M. The foamability of WPI increased
      when NaCl concentration rose from 0 to 0.1 M, and decreased with further increase
      in NaCl concentration. NaCl at low concentration (I < or = 0.4) did not show a
      significant effect on the competitive adsorption among milk proteins, indicating
      that electrostatic interactions do not play a key role in competitive adsorption.
      NaCl at higher concentration, e.g., 0.6 M, caused less whey protein to be
      adsorbed to the air/water interfaces. The whippability of WPI was highest at pH
      4.5 and lowest at pH 3, and that of SMP was the opposite. The proportions of beta
      lactoglobulin and alpha-lactalbumin in the foam phase were lower at acidic pH and
      higher at basic pH, compared with that at natural pH of WPI.

PMID- 15261082
TI  - On the mechanism of stomatocyte-echinocyte transformations of red blood cells:
      experiment and theoretical model.
AB  - This study represents an attempt to achieve a better understanding of the
      stomatocyte-echinocyte transition in the shape of red blood cells. We determined
      experimentally the index of cell shape at various ionic strengths and
      osmolarities for native and trypsin-treated human erythrocytes. For every given
      composition of the outer phase, we calculated the ionic strength in the cells and
      the transmembrane electric potential using a known theoretical model. Next, we
      described theoretically the electric double layers formed on both sides of the
      cell membrane, and derived expressions for the tensions of the two membrane
      leaflets. Taking into account that the cell-shape index depends on the tension
      difference between the two leaflets, we fitted the experimental data with the
      constructed physicochemical model. The model, which agrees well with the
      experiment, indicates that the tension difference between the two leaflets is
      governed by the different adsorptions of counterions at the two membrane
      surfaces, rather than by the direct contribution of the electric double layers to
      the membrane tension. Thus, with the rise of the ionic strength, the counterion
      adsorption increases stronger at the outer leaflet, whose stretching surface
      pressure becomes greater, and whose area expands relative to that of the inner
      leaflet. Hence, there is no contradiction between the bilayer-couple hypothesis
      and the electric double layer theory, if the latter is upgraded to account for
      the effect of counterion-adsorption on the membrane tension. The developed
      quantitative model can be applied to predict the shape index of cells upon a
      stomatocyte-discocyte-echinocyte transformation at varying composition of the
      outer medium.

PMID- 15261083
TI  - Kinetic study on the elastic change of vascular endothelial cells on collagen
      matrices by atomic force microscopy.
AB  - The elasticity of vascular endothelial cells (HUVEC) was measured with an atomic
      force microscopy (AFM, Olympus), and analyzed by applying the Hertz model, and
      those data were compared with ones reported by us previously. The latter
      elasticity data were measured with AFM Instruments (Seiko) on the basis of the
      Young's modulus of gelatin gel, which was obtained from the measurement with a
      tensile tester. The elasticity of HUVEC was concluded to depend on the culture
      period. The elasticity of the cells cultured on type IV collagen for longer than
      4 days led to average elasticity values higher than ca. 10(4)Pa. Moreover, the
      scattered values of elasticity decreased eminently in the AFM measurement of the
      cells at room temperature. A few cells, however, appeared to adhere long and
      tensely on matrix, which seems to one of reasons for relatively high elasticity
      in our previous works. The possibility of such high elasticity was considered to
      change in cell adhesion, anchoring on matrix during a long culture period.

PMID- 15261084
TI  - Research on solid-state fermentation on rice chaff with a microbial consortium.
AB  - A microbial consortium of Trichoderma reesei AS3.3711, Aspergillus niger 3.316
      and Saccharomyces cerevisiaes AS2.399 was constructed to decomposed rice chaff on
      the basis of the characters of each microorganism and the mechanism of
      cellulases. In this experiment, rice chaff was pretreated before fermentation
      with NaOH so that the lignin structure of rice chaff was degraded and
      hemicellulose was dissolved partly, which remove the protection of lignin and
      hemicellulose on cellulose and demolish its special crystal structure. After
      pretreatment, rice chaff can be degraded more easily with the microbial
      consortium. The optimal technical paths and technological methods were achieved
      for intenerating rice chaff with the microbial consortium perfectly through
      orthogonal experiment. According to the technological methods, some experiments
      were done at 30 degrees C with pH 4.5. It was found that the highest filter paper
      enzyme activity (FPA) was 5.64 U/g and the ratio of cellulose degradation (RCD)
      was 28.05%.

PMID- 15261085
TI  - Effect of low frequency ultrasonic stimulation on the secretion of siboflavin
      produced by Ecemothecium Ashbyii.
AB  - The structure of the cell membrane of Ecemothecium ashbyii is considered to be
      one of the main obstacles in the improvement of riboflavin productivity, which
      impedes the release of riboflavin from the cell into the fermentation broth. The
      results of the present study show that stimulation on growth and riboflavin
      biosynthesis phase, the content of riboflavin was most obviously enhanced, as
      compared with the control and the total riboflavin quantity released by
      ultrasonic treatment. The optimal stimulation time was from 104 to 112 h and
      ultrasonic should be loaded every 1.5 h.

PMID- 15261086
TI  - Electrostatic effects on the yield stress of whey protein isolate foams.
AB  - The mechanisms responsible for foam structure are of practical interest within
      the food industry. The yield stress (tau) of whey protein isolate (WPI) foams as
      affected by electrostatic forces was investigated by whipping 10% (w/v) protein
      solutions prepared over a range of pH levels and salt concentrations.
      Measurements of foam overrun and model WPI interfaces, i.e. adsorption kinetics
      as determined via dynamic surface tension and dilatational rheological
      characterization, aided data interpretation. Interfacial measurements were also
      made with the primary whey proteins, beta-lactoglobulin (beta-lg) and alpha
      lactalbumin (alpha-la). Yield stress of WPI foams was dependent on pH, salt type
      and salt concentration. In the absence of salt, tau was highest at pH 5.0 and
      lowest at pH 3.0. The addition of NaCl and CaCl2 up to 400 mM significantly
      increased tau at pH 7.0 but not at pH 3.0. Furthermore, at pH 7.0, equivalent
      molar concentrations of CaCl2 as compared to NaCl increased tau to greater
      extents. Salts had minimal effects on tau at pH 5.0. Comparisons with interfacial
      rheological data suggested the protein's capacity to contribute towards tau was
      related to the protein's potential at forming strong, elastic interfaces
      throughout the structure. The dynamic surface tension data for beta-lg and alpha
      la were similar to WPI, while the interfacial rheological data displayed several
      noticeable differences.

PMID- 15261087
TI  - A quantitative contour analysis of axisymmetric vesicles spontaneously adhering
      onto a substrate.
AB  - The determination of membrane-substrate profile for adherent vesicle using
      confocal reflectance interference contrast microscopy (C-RICM) has pushed for the
      need of advanced mechanics model for interpreting adhesion mechanisms. In this
      work, a model for vesicles or cells adhesion is established, the governing
      equation is derived from the variation of the potential energy at the cohesive
      zone. A closed-form solution is found for vesicle spontaneously adheres to a
      substrate when its shear modulus, micro vanishes. Based on the model and C-RICM
      experiments the magnitude of the adhesion force is calculated for a lipid vesicle
      adheres to a glass substrate.

PMID- 15261088
TI  - Study of the lignin model compound supramolecular structure by combination of
      near-field scanning optical microscopy and atomic force microscopy.
AB  - In this paper, we present a nanoscale study of the supramolecular structure of
      the dehydrogenate polymer (ZL-DHP) lignin model compound. The combination of near
      field scanning optical microscopy (NSOM or SNOM) and atomic force microscopy
      (AFM) has been utilized to explore physicochemical properties of the lignin model
      compound on a scale ranging from individual macromolecules to globular
      supramolecular assemblies. By utilizing NSOM in transmission mode, the optical
      inhomogeneity in the lignin supramolecular structure has been observed for the
      first time. In particular, the transmission-mode NSOM images reveal a combination
      of hollow and layered supramolecular globular structure in the lignin model
      compound. Through the paired use of TappingMode and pulsed-mode AFM, we have also
      confirmed the existence of regions with different rheological properties on the
      single lignin model compound supramolecular assembly.

PMID- 15261089
TI  - Probing small unilamellar EggPC vesicles on mica surface by atomic force
      microscopy.
AB  - Sonicated small unilamellar egg yolk phosphatidylcholine (EggPC) vesicles were
      investigated using atomic force microscopy (AFM) imaging and force measurements.
      Three different topographies (convex, planar, and concave shape) of the EggPC
      vesicles on the mica surface were observed by tapping mode in fluid,
      respectively. It was found that the topography change of the vesicles could be
      attributed to the interaction force between the AFM tip and vesicles. Force
      curves between an AFM tip and an unruptured vesicle were obtained in contact
      mode. During approach, two breaks corresponding to the abrupt penetration of
      upper and lower bilayer of vesicle were exhibited in the force curve. Both breaks
      spanned a distance of around 4 nm close to the EggPC bilayer thickness. Based on
      Hertz analysis of AFM approach force curves, the Young's modulus (E) and the
      bending modulus (kc) for pure EggPC vesicles were measured to be (1.97 +/- 0.75)
      x 10(6)Pa and (0.21 +/- 0.08) x 10(-19)J, respectively. The results show that the
      AFM can be used to obtain good images of intact and deformed vesicles by tapping
      mode, as well as to probe the integrity and bilayer structure of the vesicles.
      AFM force curve compare favorably with other methods to measure mechanical
      properties of soft samples with higher spatial resolution.

PMID- 15261090
TI  - Gliadin effect on fluctuation properties of phospholipid giant vesicles.
AB  - Gliadin is a fraction of wheat gluten, a protein supramolecular complex known for
      its remarkable and biotechnologically relevant viscoelastic properties. Very high
      molecular mass characterise these systems, thus hindering high-resolution
      structural investigations. It is known, however, that these proteins comprise
      rather extended, extensively interassociated structures, which respond for their
      peculiar mechanical behaviour. Besides these properties, some of gluten's
      fractions, such as gliadin, are also known to be involved in a nutritionally
      relevant pathology of auto-immune character, the celiac disease, supposedly
      related to some unusual structural features of the protein. Despite its medical
      relevance, however, the role played by gliadin in the etiology of the celiac
      disease is not sufficiently understood to date. In this work, we investigated the
      role of gliadin on mechanical properties of a membrane model of
      dioleoylphosphatidylcholine (DOPC) giant unilamellar vesicles. The technique of
      micropipette aspiration, coupled to videomicroscopy, was applied. The
      microvesicles, produced by electric field pulsing over metal-covered plates, were
      suctioned into the micropipettes under varying applied pressures. A significant
      increase in the values of the bilayer curvature constant, k(c), was observed,
      with a saturation effect being verified at around 0.02-0.03 gliadin/DOPC mass
      ratio, indicating that the membrane becomes less elastic in the presence of the
      protein. Possible correlations between the observed membrane fluctuation
      properties and the celiac disease etiology are suggested and discussed.

PMID- 15261091
TI  - Study on the interaction between nucleic acids and cationic surfactants.
AB  - The interactions of nucleic acids and cationic surfactants (cetylpyridine bromide
      (CPB) and cetyltrimethylammonium bromide (CTMAB)) in aqueous solution have been
      studied using the techniques of resonance light scattering (RLS) spectroscopy,
      the absorption spectroscopy, zeta potential assay and NMR assignment measurement.
      It is considered that CPB or CTMAB can assemble on the surface of nucleic acid
      via electrostatic and hydrophobic forces, which results in the formation of large
      associate of nucleic acid-cationic surfactant and RLS enhancement of nucleic
      acid. Besides these forces, the pi-pi stacking force between CPB and nucleic acid
      also exists in the associate. In comparison with CTMAB, CPB has larger
      enhancement on RLS of nucleic acid, which is attributed to that the enhancement
      of the former is only due to the absorption of the bases of nucleic acid, while
      the enhancement of the latter is own to the synergetic resonance caused by the
      absorption of both bases of nucleic acid and the pyridyl in CPB. These results
      have important implication for understanding the influence of surfactants on
      nucleic acid functionality in life science.

PMID- 15261092
TI  - Effect of membrane composition on surface states of ganglioside
      GM1/dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine monolayers.
AB  - The surface states of ganglioside GM1 (GM1)/dipalmitoylphosphatidylcholine
      (DPPC)/dioleoylphosphatidylcholine (DOPC) monolayers having various compositions
      were investigated using atomic force microscopy (AFM), and the effect of the
      composition on the surface states of the membrane was examined. The AFM images
      for the ternary system showed a DPPC-rich phase containing GM1 in the DOPC
      matrix, which indicated that the morphology varied as the composition of the
      monolayers changed. The AFM images for the GM1/DPPC/DOPC monolayers having
      (2:9:9) and (4:18:9) molar ratios showed a percolation pattern similar to that
      observed for the GM1/DPPC (1:9) monolayer. The AFM image for the GM1/DPPC/DOPC
      (2:18:9) monolayer showed a dotted pattern with a high topography. Monolayers
      having a higher content of DOPC than DPPC and/or having a higher content of GM1
      showed dot-like domains in the DPPC-rich phase containing GM1. In conclusion, the
      surface states of GM1/DPPC/DOPC monolayers changed depending on the composition.
      These results may be related to a diversity of GM1 in various organs.

PMID- 15261093
TI  - Short-term effects of the nociceptin receptor antagonist Compound B on the
      development of methamphetamine sensitization in mice: a behavioral and c-fos
      expression mapping study.
AB  - The nociceptin antagonist Compound B (CompB) stimulates mesolimbic dopamine
      release and induces a conditioned place preference but has little effect on
      locomotion. As behavioral sensitization often occurs as an epiphenomenon to
      mesolimbic activation and reward, we studied the effect of CompB on behavioral
      sensitization to methamphetamine. Locomotor responses of C57BL6 mice to repeated
      methamphetamine (2 mg/kg s.c.) administration alone or immediately following
      CompB (10 mg/kg s.c.) were recorded for 3 alternating days. Six days later,
      methamphetamine (1 mg/kg s.c.) was administered and locomotor activity monitored
      again before determining neural activity by analysis of c-fos expression.
      Methamphetamine treatment induced a progressive locomotor (behavioral)
      sensitization, with CompB pretreatment enhancing the locomotor response to
      methamphetamine during the early stages only. Previous CompB administration
      little affected methamphetamine-sensitized or acute methamphetamine-induced
      locomotion on the challenge day. Analysis of c-fos expression supported these
      results as of the 36 neuroanatomical regions quantified; very few showed CompB
      dependent responses. However, numerous regions differentially responsive to
      either acute (e.g. ventromedial, ventrolateral and central caudate putamen),
      chronic (e.g. central amygdala, lateral habenula, dorsomedial caudate putamen) or
      sensitized (e.g. medial nucleus accumbens core, central amygdala, lateral
      habenula) methamphetamine treatment were identified, thereby providing a
      comprehensive map of the short and long-term effects of methamphetamine on mouse
      brain activity per se. Thus, despite its mesolimbic activating and rewarding
      properties, CompB has little long-term influence on neural activity, suggesting
      CompB is able to induce short-term increases in hedonic state in the absence of
      locomotion or major long-term effects.

PMID- 15261094
TI  - Firing rates and dynamic correlated activities of ganglion cells both contribute
      to retinal information processing.
AB  - In the present study, the electrical activities of paired retinal ganglion cells,
      under full field light stimuli with a variety of chromatic configurations, were
      recorded from a small functioning piece of retina using multi-electrode array
      (MEA). Neurons that had increased firings at light-ON and -OFF transients and did
      not show color-opponent properties were investigated. Single neuronal analysis
      showed that firing rate of each individual neuron was dependent on the intensity
      of illumination. Multi-unit analyses revealed that adjacent neurons often fired
      in synchrony in response to light stimulation. However, in some cases, the
      strength of correlation between the paired neurons was higher when the retina was
      exposed to red or green light, and the correlation was attenuated when yellow or
      white light was given. This seems to suggest that the ensemble activity of non
      color-opponent ganglion cells might partly participate in color-information
      processing, with the red- and green-pathway inputs influencing each other. Such
      arrangement reflects principle of parsimony: the firing rates of single neuron
      represent the luminance intensity, and the correlated activities may tell the
      brain about the color information.

PMID- 15261095
TI  - Morpho-functional characterization of neuronal cells at different stages of
      maturation in granule cell layer of adult rat dentate gyrus.
AB  - Neurogenesis occurs throughout adult life in dentate gyrus of mammal hippocampus.
      Therefore, neurons at different stages of electrophysiological and morphological
      maturation and showing various, if any, synaptic inputs co-exist in the adult
      granule cell layer, as occurs during dentate gyrus development. The knowledge of
      functional properties of new neurons throughout their maturation can contribute
      to understanding their role in the hippocampal function. In this study
      electrophysiological and morphological features of granule layer cells,
      characterized as immature or mature neurons, without and with synaptic input,
      were comparatively described in adult rats. The patch-clamp technique was used to
      perform electrophysiological recordings, the occurrence of synaptic input evoked
      by medial perforant pathway stimulation was investigated and synaptic input was
      characterized. Cells were then identified and morphologically described via
      detection of biocytin injected through the patch pipette. The neuronal phenotype
      of recorded cells was assessed by immunohistochemistry and single-cell RT-PCR.
      Cells with very low capacitance, high input resistance, depolarized resting
      membrane potential and without synaptic activity were found exclusively at the
      border of the GCL facing hilus; this type of cell expressed the class III beta
      tubulin neuronal marker (mRNA and protein) and did not express a glial marker.
      Immature neuronal cells with progressively increasing capacitance, decreasing
      input resistance and resting membrane potential getting more hyperpolarized
      showed only depolarizing GABAergic synaptic input at first and then also
      glutamatergic synaptic input. Finally, cells showing electrophysiological,
      synaptic, and morphological features of mature granule, expressing the mature
      neuron marker NeuN, were identified.

PMID- 15261096
TI  - Occurrence of limb movement during sleep in rats with spinal cord injury.
AB  - Several studies have shown the occurrence of Periodic Leg Movement (PLM) in
      spinal cord injury patients. The aim of this study was to identify the occurrence
      of limb movements during sleep in spinal cord injury rats and the possible
      involvement of the spinal cord in causing these movements. The animals were
      allocated to spinal cord injury (SCI) and SHAM groups. The two groups were
      submitted to surgery and electrodes inserted to analyze sleep patterns
      (electroencephalogram-ECoG) and muscular activity patterns (eletromyogram-EMG).
      After baseline sleep recording (24 h), the spinal cord injury surgery (level T9)
      was performed on the SCI group rats and sleep was recorded for seven consecutive
      days. After spinal cord injury, 10 of the 11 rats began to present limb movements
      during sleep, while the SHAM group showed no limb movements during the 8-day
      sleep-recording period. In relation to sleep efficiency, the SCI group presented
      alterations during the first few days after spinal cord injury but returned to
      normal values at the end of the 7-day experimental period. The data suggest that
      spinal cord injury rats may be used as models to study PLM in paraplegic
      patients, and that these movements may be generated in the spinal cord itself,
      without the involvement of the cortical structures.

PMID- 15261097
TI  - Nitric oxide pathway in the nucleus raphe magnus modulates hypoxic ventilatory
      response but not anapyrexia in rats.
AB  - Nucleus raphe magnus (NRM) is one of the cellular groups of the brainstem that is
      involved in the physiologic responses to hypoxia and contains nitric oxide (NO)
      synthase. In the present study, we assessed the role of NO pathway in the NRM on
      the hypoxic ventilatory response (HVR) and anapyrexia (a regulated decrease in
      body temperature). To this end, pulmonary ventilation (VE) and body temperature
      (Tb) of male Wistar rats were measured before and after microinjection of N
      monomethyl-L-arginine (L-NMMA, a nonselective nitric oxide synthase inhibitor,
      12.5 microg/0.1 microl) into the NRM, followed by hypoxia. Control rats received
      microinjection of saline. Under resting conditions, L-NMMA treatment did not
      affect pulmonary VE or Tb. Typical hypoxia-induced hyperventilation and
      anapyrexia were observed after saline treatment. L-NMMA into the NRM reduced the
      HVR but did not affect hypoxia-induced anapyrexia. In conclusion, the present
      study indicates that NO in the NRM is involved in HVR, exerts an inhibitory
      modulation on the NRM neurons but does not mediate hypoxia-induced anapyrexia.

PMID- 15261098
TI  - Localization of TREK-1, a two-pore-domain K+ channel in the peripheral vestibular
      system of mouse and rat.
AB  - The distribution of two-pore-domain (2P-domain) K(+) channels of the TREK
      subfamily was studied using immunocytochemistry in the peripheral vestibular
      system of mouse and rat. Using RT-PCR, the mRNA for TREK-1, but not for TREK-2 or
      TRAAK, were detected in mouse vestibular endorgans and ganglia. The TREK-1
      channel protein was immunodetected in both nerve fibers and nerve cell bodies in
      the vestibular ganglion, both afferent fibers and nerve calyces innervating type
      I hair cells in the utricle and cristae. The post-synaptic localization in
      afferent calyces may suggest a neuroprotective role in glutamatergic
      excitotoxicity during ischemic conditions. In non-neuronal cells, TREK-1 was
      immunodetected in the apical membrane of dark cells and transitional cells, both
      of which are involved in endolymph K(+) secretion and recycling. TREK-1 may
      subserve some neuroprotective function in afferent nerve fibers as well as play a
      role in endolymph potassium homeostasis.

PMID- 15261099
TI  - Brain capillary endothelial cells proliferate in response to NGF, express NGF
      receptors and secrete NGF after inflammation.
AB  - Nerve growth factor (NGF) is an important factor regulating survival in
      development and during regenerative or neuroinflammatory processes. The aim of
      this study was to investigate whether brain capillary endothelial cells (BCEC)
      respond to NGF and whether pro-inflammatory substances induce the secretion of
      NGF in these cells. Cells were incubated with the growth factors NGF or vascular
      endothelial growth factor or endothelial cell growth factor, and proliferation
      was observed by incorporation of 5-bromo-2'-deoxy-uridine. NGF-secretion was
      measured by ELISA and expression of the NGF-receptors trkA and p75(NTR) by
      Western blot. Proliferation of BCEC was enhanced by exogenous NGF (1-100 ng/ml.).
      BCEC expressed NGF receptors in vivo (P3, P10, P20, adult) and displayed
      secretion of endogenous NGF ( approximately 20 pg/ml) into the medium. Treatment
      of BCEC with the proinflammatory cytokine interleukin-1beta+lipopolysaccharide
      enhanced expression of p75(NTR) and the secretion of NGF ( approximately 35
      pg/ml). The effects of NGF were blocked by anti-NGF antibodies (5 microg/ml). In
      summary, NGF shows proliferative activity in BCEC, and NGF is secreted after
      inflammation. Therefore, the NGF pathway can modulate BCEC and may influence
      blood-brain barrier functions.

PMID- 15261100
TI  - Dynamics of the contralateral white noise-induced enhancement in the guinea pig's
      middle latency response.
AB  - The peak-to-peak amplitude of temporal middle latency response (MLR) of the
      guinea pig, evoked by a click in the contralateral ear, according to the
      recording side, is increased with the presence of continuous white noise (CWN) in
      the ipsilateral ear and this specialty is defined as the white noise enhancement
      (WNE). This phenomenon is evaluated as an interesting electrophysiological
      finding from the viewpoint of binaural interaction and in this study, its dynamic
      specifications were investigated. After the beginning of ipsilateral CWN,
      significant WNE was observed at 275th ms and it reached to a maximum, with an
      increase more than 40%, at 350th ms. After a habituation occurred, WNE reached to
      20% on the 4th second by gradually decreasing and came to a steady state. In the
      time window between 2 and 5 ms after CWN started, a surprising amplitude decrease
      is observed. Therefore, CWN causes an effect, like a click, in the short-term and
      this on-response type effect originates from low level binaural centers, which
      decreases the MLR amplitude. However, the same CWN increases the MLR amplitude
      (WNE) by the effects over the high level binaural centers in the succeeding
      period, by its continuous characteristic.

PMID- 15261101
TI  - Peripheral axotomy induces depletion of the vesicular glutamate transporter
      VGLUT1 in central terminals of myelinated afferent fibres in the rat spinal cord.
AB  - Myelinated primary afferent axons use glutamate as their principal
      neurotransmitter. We have shown previously that central terminals of myelinated
      tactile and proprioceptive afferents contain the vesicular glutamate transporter
      VGLUT1. Peripheral nerve injury is known to induce changes in the anatomy,
      neurochemistry, and physiology of primary afferents. In this study, we have
      examined the effect of peripheral axotomy on VGLUT1 expression in central
      terminals of myelinated afferents in laminae III-V and lamina IX of the rat
      spinal cord. Bilateral injections of cholera toxin B subunit (CTb) were made into
      the sciatic nerves of rats that had undergone unilateral sciatic nerve
      transection 1, 2, 4, or 8 weeks previously. Immunofluorescence staining and
      confocal microscopy were used to compare levels of VGLUT1 in CTb-labelled boutons
      on the intact and sectioned sides at each postoperative survival time. VGLUT1 was
      depleted from central terminals of transected myelinated afferents in rats
      injected with CTb 1 week after nerve section, and this depletion became more
      severe in animals with longer postaxotomy survival times. By 4 weeks, the level
      of VGLUT1 in CTb-labelled boutons in lamina IX was reduced by over 80% compared
      to that seen in intact (contralateral) afferents, while for boutons in laminae
      III-V, VGLUT1 levels were reduced by 50-70%. This suggests that loss of VGLUT1 is
      more severe in proprioceptive than cutaneous afferents. Depletion of VGLUT1 may
      lead to a decrease in levels of transmitter glutamate in these afferents and thus
      to a reduction in synaptic efficacy.

PMID- 15261102
TI  - Age-related changes of gamma-aminobutyric acid transaminase immunoreactivity in
      the hippocampus and dentate gyrus of the Mongolian gerbil.
AB  - We investigated the age-related changes of gamma-aminobutyric acid transaminase
      (GABA-T, a GABA degradation enzyme) in the hippocampus and dentate gyrus of the
      gerbil at postnatal month 1 (PM 1), PM 3, PM 6, PM 12, and PM 24. Age-related
      changes of GABA-T immunoreactivity were distinct in the hippocampal CA1 region
      and in the dentate gyrus. GABA-T immunoreactivity was weak at PM 1, but at PM 3,
      it had increased significantly, and then increased further. Between PM 6 and PM
      12, strong GABA-T immunoreactivity was found in nonpyramidal cells (GABAergic) in
      the stratum pyramidale of the CA1 region, and at PM 6, strong GABA-T
      immunoreactivity was found in neurons of the dentate gyrus subgranular zone. At
      PM 24, CA1 pyramidal cells showed strong GABA-T immunoreactivity. Western blot
      analysis showed a pattern of GABA-T expression similar to that shown by
      immunohistochemistry at various ages. In conclusion, our results suggest that the
      age-related changes of GABA-T provide important information about the aged brain
      with GABA dysfunction.

PMID- 15261103
TI  - Regulated hypothermia reduces brain oxidative stress after hypoxic-ischemia.
AB  - Regulated hypothermia produces a decrease in core temperature by lowering the
      brain's temperature set-point while maintaining thermoregulation at that lower
      set point. In contrast, forced hypothermia lowers core temperature by
      overwhelming the body's capacity to thermoregulate, but does not change the set
      point. Regulated hypothermia has been shown to be cerebral protective in
      hibernating mammals. The effect of regulated hypothermia on the brain during
      reperfusion from hypoxic-ischemia has not been well studied. We induced regulated
      hypothermia with a neurotensin analogue (NT77) to determine whether it could
      reduce oxidative stress in the brain during reperfusion from asphyxial cardiac
      arrest (ACA) in rats. Mild hypothermia (32-34 degrees C) was induced by brief (4
      h) external cooling (BC), NT77 or prolonged external cooling (24 h) (PC) 30 min
      after resuscitation from 8 min of ACA in rats. Malondialdehyde (MDA) levels in
      the brain were measured during reperfusion to quantitate oxidative stress.
      RESULTS: MDA levels in the hippocampus were elevated at 16 h of normothermic
      reperfusion versus 48 h with BC reperfusion. There was no increase in hippocampal
      MDA levels in the NT77 and PC groups at 24-72 h of reperfusion. Regulated
      hypothermia induced by NT77 reduced oxidative stress in the hippocampus during
      reperfusion from hypoxic-ischemia in comparison to forced brief external cooling
      of the same duration. In addition, the duration of external cooling after
      resuscitation also alters oxidative stress in the brain during reperfusion.

PMID- 15261104
TI  - Therapeutic time window for the neuroprotective action of MK-801 after
      decapitation ischemia: hippocampal slice data.
AB  - Neuroprotective action of MK-801 administrated pre- and postischemically, in vivo
      or in vitro, respectively, was studied on hippocampal slices using decapitation
      ischemia model. Recovery of orthodromic population spikes in CA1 region was
      measured during postischemic incubation of the slices with oxygenated artificial
      cerebrospinal fluid (ACSF). The ability of postischemically applied MK-801 to
      restore the electrical activity dramatically depended on the timing of its
      application during the reoxygenation period. When applied in vitro, together with
      the start of reoxygenation, MK-801 was as effective as in the case of in vivo
      administration before the ischemia. The delay in the in vitro administration for
      only a few minutes led to a dramatic decrease in the drug effectiveness. When
      applied in 30 min after the start of reoxygenation, MK-801 was totally
      ineffective. The dose/response relationship between MK-801 concentration and the
      amplitude of recovered orthodromic population spikes of hippocampal pyramidal
      neurons is logarithmic. The ED(50) value for the action of "postischemic" MK-801
      is ca. 10(-5) M. Preischemic in vivo application of the drug [intraperitoneal
      (i.p.) injection 15 min prior to decapitation] results in ED(50) ca. 0,2 mg/kg.
      The slope of both dose/concentration-response curves is similar. The time course
      of population spike recovery after 90-min ischemia is identical for pre- and
      postischemic action of MK-801 (estimated for ED(50) in both cases). These data
      allow to suggest that "preischemic" MK-801 is predominantly active as a
      neuroprotector only after ischemia, within a short therapeutic window at the
      start of the reoxygenation period.

PMID- 15261105
TI  - Oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene) is neuroprotective and
      inhibits the apoptotic cell death in transient cerebral ischemia.
AB  - Oxidative stress is one of the major pathological factors in the cascade that
      leads to cell death in cerebral ischemia. Here, we investigated the
      neuroprotective effect of a naturally occurring antioxidant, oxyresveratrol, to
      reduce brain injury after cerebral stroke. We used the transient rat middle
      cerebral artery occlusion (MCAO) model of brain ischemia to induce a defined
      brain infarction. Oxyresveratrol was given twice intraperitoneally: immediately
      after occlusion and at the time of reperfusion. Oxyresveratrol (10 or 20 mg/kg)
      significantly reduced the brain infarct volume by approximately 54% and 63%,
      respectively, when compared to vehicle-treated MCAO rats. Also, the neurological
      deficits as assessed by different scoring methods improved in oxyresveratrol
      treated MCAO rats. Histological analysis of apoptotic markers in the ischemic
      brain area revealed that oxyresveratrol treatment diminished cytochrome c release
      and decreased caspase-3 activation in MCAO rats. Also, staining for apoptotic DNA
      showed that the number of apoptotic nuclei in ischemic brain was reduced after
      oxyresveratrol treatment as compared to the vehicle-treated MCAO rats. This dose
      dependent neuroprotective effect of oxyresveratrol in an in vivo stroke model
      demonstrates that this drug may prove to be beneficial for a therapeutic strategy
      to limit brain injury in acute brain ischemia.

PMID- 15261106
TI  - Activation of protein kinase C antagonizes the opioid inhibition of calcium
      current in rat spinal dorsal horn neurons.
AB  - Spinal dorsal horn (SDH) is one of important regions in both nociceptive
      transmission and antinociception. Opioid peptides produce analgesia via
      regulation of neurotransmitter release through modulation of voltage-dependent
      Ca(2+) channel (VDCC) in neuronal tissues. The modulatory effect of micro-opioid
      receptor (MOR) activation on VDCC was investigated in acutely isolated rat SDH
      neurons under the conventional whole-cell patch-clamp recording mode. The Ba(2+)
      current passing through VDCC was reversibly inhibited by a MOR agonist, [D
      Ala(2),N-MePhe(4),Gly(5)-ol]-enkephalin (DAMGO, 1 microM). Among 108 SDH neurons
      tested, VDCC of 39 neurons (36%) were inhibited by MOR activation, while other 69
      neurons (64%) were not affected. The L-, N-, P/Q-, and R-type VDCC components
      shared 58.4+/-18.9%, 29.3+/-12.1%, 8.7+/-7.2%, and 3.4+/-4.8% of the total VDCC,
      respectively. Among VDCC subtypes inhibited by MOR activation, L- and N-types
      were 61.4+/-12.8% and 30.7+/-14.4%, respectively, while both P/Q- and R-types
      were 7.9+/-11.8%. A depolarizing pre-pulse increased the amplitude of VDCC and
      suppressed most of the inhibitory effect of MOR activation. Application of 1
      microM phorbol-12-myristate-13-acetate completely antagonized the inhibitory
      effect of MOR activation without any alteration of basal VDCC amplitude. In
      contrast, the response of MOR activation was not altered by application of 4
      alpha-phorbol (1 microM), 2-[3-Dimethylaminopropyl]indol-3-yl]-3-(indol-3-yl)
      maleimide (GF109203X, 1 microM), forskolin (1 microM), N-(2-[p
      Bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89, 1
      microM). These results indicate that activation of MOR coupled to G-proteins
      inhibits VDCC, and that this G-protein-mediated inhibition is antagonized by PKC
      dependent phosphorylation.

PMID- 15261107
TI  - Evidence for a differential medial prefrontal dopamine D1 and D2 receptor
      regulation of local and ventral tegmental glutamate and GABA release: a dual
      probe microdialysis study in the awake rat.
AB  - The effects of perfusion with two selective dopamine receptor agonists SKF38393
      and pergolide into the medial prefrontal cortex (mPfc) on local and ventral
      tegmental area (VTA) glutamate and gamma-aminobutyric acid (GABA) release were
      investigated using dual probe microdialysis in the awake rat. Intracortical
      SKF38393 (10, 100, 500 microM, 60 min) decreased glutamate and increased GABA
      release in the mPfc but had no effect on either amino acid neurotransmitter in
      the VTA. Intracortical perfusion with the selective GABA(A) receptor antagonist
      bicuculline (0.1 microM, 140 min) reversed the SKF38393 (100 microM, 60 min)
      induced decrease in local glutamate release, while the selective GABA(B) receptor
      antagonist CGP35348 (100 microM, 140 min) was without effect. Intracortical
      pergolide (1 microM, 60 min) was associated with a prolonged reversible decrease
      in local and VTA glutamate release that was also associated with a decrease in
      VTA GABA release, which was reversed in the presence of intracortical raclopride
      (10 microM, 140 min). Taken together, the present findings indicate a
      differential regulation of glutamate and GABA release in the mPfc and VTA by
      dopamine D(1) and D(2) receptors in the mPfc whereby (a) activation of the
      dopamine D(1) receptor in the mPfc decreases local glutamate release possibly via
      a feed-forward activation of the local GABA interneurons; (b) activation of the
      dopamine D(2) receptor in the mPfc inhibits both local glutamate release and the
      excitatory glutamate drive on the VTA.

PMID- 15261108
TI  - Cognitive correlates of Abeta deposition in male and female mice bearing amyloid
      precursor protein and presenilin-1 mutant transgenes.
AB  - Several transgenic mouse models of Alzheimer's disease (AD) have been developed
      that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits.
      However, not all studies have investigated the relationship between the
      development of cognitive impairment and neuropathology. Therefore, temporal
      changes in cognition were investigated in male and female double-mutant
      APPswexPS1.M146V (TASTPM) transgenic mice using an object recognition test and
      correlated with the development of cerebral Abeta neuropathology. Both male and
      female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and
      10 months of age in the object recognition test, compared to wild-type
      littermates. There was no such cognitive impairment at 3 or 4 months of age.
      Quantitative immunohistochemistry using a battery of Abeta antibodies
      demonstrated that cerebral Abeta deposition was first apparent in 3-month-old
      mice, and it increased with age. The early appearance of cerebral Abeta deposits
      in the double-transgenic TASTPM mice supports the evidence that mutations in the
      PS1 gene accelerate Abeta deposition. The cerebral Abeta load was greater in
      female than in male TASTPM mice at all ages investigated. In the electron
      microscope, mature Abeta plaques comprising a fibrillar core surrounded by
      degenerating neurites and reactive glia were first observed in the cortex of
      TASTPM mice at 6 months of age, the same age at which cognitive impairment became
      apparent. These results suggest that the cognitive impairment in TASTPM mice is
      related to the disruption of neural connectivity and not simply Abeta deposition,
      which first occurs 3 months earlier.

PMID- 15261109
TI  - Intracellular pH and KATP channel activity in dorsal vagal neurons of juvenile
      rats in situ during metabolic disturbances.
AB  - Intracellular pH (pH(i)) is an important factor for understanding cellular
      processes associated with the response of central neurons to metabolic
      disturbances such as anoxia or ischemia. In the present study, pH(i) was
      fluorometrically measured in 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescin
      (BCECF)-filled, voltage-clamped dorsal vagal neurons (DVN) of brainstem slices
      from rats during metabolic disturbances activating ATP-sensitive K(+) (K(ATP))
      channels. Chemical anoxia induced by cyanide, rotenone or p-trifluoromethoxy
      phenylhydrazone (FCCP) decreased pH(i) by >0.4 pH units. Untreated neurons with
      normal pH(i) baseline (7.2) responded to glucose-free superfusate after a delay
      of 7-16 min with a progressive fall of pH(i). In contrast, pH(i) increased by
      >0.2 pH units after approximately 10 min in cells that had a mean pH(i) of 6.8
      due to incomplete recovery from a CN(-)induced acid load prior to glucose
      depletion. Metabolic arrest, induced by cyanide in glucose-free solution after 30
      min preincubation in glucose-free saline, caused a progressive glutamate-mediated
      inward current with no change of pH(i). Upon metabolic arrest, depolarization
      evoked pH(i) decreases ( approximately 0.2 pH units) were abolished, whereas
      glucose-free superfusate slightly delayed their recovery without major effects on
      amplitude. The glucose-dependent pH(i) fall coincided with activation of the
      K(ATP) channel-mediated outward current, while K(ATP) currents due to anoxia or
      metabolic arrest could reach their maximum in the absence of a major pH(i)
      change. The results indicate that the anoxic pH(i) decrease is due to enhanced
      glycolysis and lactate formation with often no obvious effect on K(ATP) channel
      activity. The origin of glucose-dependent acidosis and its relation to K(ATP)
      channel activity remain to be determined.

PMID- 15261110
TI  - The protective effect of hypoxic preconditioning on cortical neuronal cultures is
      associated with increases in the activity of several antioxidant enzymes.
AB  - Preconditioning describes a variety of treatments that induce neurons to become
      more resistant to a subsequent ischemic insult. How preconditioned neurons adapt
      to subsequent ischemic stress is not fully understood, but is likely to involve
      multiple protective mechanisms. We hypothesized hypoxic preconditioning induces
      protection by a coordinated up-regulation of antioxidant enzyme activity. To test
      this hypothesis, we developed two in vitro models of ischemia/reperfusion,
      involving oxygen-glucose deprivation (OGD) where neuronal cell death was
      predominantly by necrosis (necrotic model) or programmed cell death (PCD model).
      Hypoxic preconditioning 24 h prior to OGD significantly reduced cell death from
      83% to 22% in the necrotic model and 68% to 11% in the PCD model. Consistent with
      the hypothesis, the activity of the antioxidant enzymes glutathione peroxidase,
      glutathione reductase, and Mn superoxide dismutase were significantly increased
      by 54%, 73% and 32%, respectively, in neuronal cultures subjected to hypoxic
      preconditioning. Furthermore, superoxide and hydrogen peroxide concentrations
      following OGD were significantly lower in the PCD model that had been subjected
      to hypoxic preconditioning.

PMID- 15261111
TI  - Regulation of TRPV2 by axotomy in sympathetic, but not sensory neurons.
AB  - Neuropathic pain results from traumatic or disease-related insults to the nervous
      system. Mechanisms that have been postulated to underlie peripheral neuropathy
      commonly implicate afferent neurons that have been damaged but still project
      centrally to the spinal cord, and/or intact neurons that interact with
      degenerating distal portions of the injured neurons. One pain state that is
      observed following peripheral nerve injury in the rat is thermal hyperalgesia.
      The noxious heat-gated ion channel TRPV1 may be responsible for this increased
      sensitivity, as it is up-regulated in L4 dorsal root ganglion (DRG) neurons
      following L5 spinal nerve lesion (SpNL). The TRPV1 homologue TRPV2 (or VRL-1) is
      another member of the TRPV subfamily of TRP ion channels. TRPV2 is a nonselective
      cation channel activated by high noxious temperatures (>52 degrees C) and is
      present in a subset of medium- to large-diameter DRG neurons. To establish
      whether TRPV2 is endogenous to the spinal cord, we examined its expression in the
      dorsal horn following rhizotomy. We found no significant decrease in TRPV2
      immunoreactivity, suggesting that TRPV2 is endogenous to the spinal cord. In
      order to determine whether TRPV2, like TRPV1, is regulated by peripheral axotomy,
      we performed L5 SpNL and characterized TRPV2 distribution in the DRG, spinal
      cord, brainstem, and sympathetic ganglia. Our results show that peripheral
      axotomy did not regulate TRPV2 in the DRG, spinal cord, or brainstem; however,
      TRPV2 was up-regulated in sympathetic postganglionic neurons following injury,
      suggesting a potential role for TRPV2 in sympathetically mediated neuropathic
      pain.

PMID- 15261112
TI  - Activity-dependent regulation of a chondroitin sulfate proteoglycan 6B4
      phosphacan/RPTPbeta in the hypothalamic supraoptic nucleus.
AB  - The hypothalamic magnocellular neurons, synthesizing arginine vasopressin (AVP)
      and oxytocin, are well known to show structural plasticity during chronic
      physiological stimulation. We have previously reported that 6B4
      phosphacan/receptor-type protein-tyrosine phosphatasebeta (RPTPbeta), a
      chondroitin sulfate proteoglycan is highly expressed in the supraoptic nucleus
      (SON) of adult hypothalamus. Here, we undertook to study the activity-dependent
      regulation of 6B4 phosphacan/RPTPbeta in this system. Double labeling confocal
      microscopy demonstrated in the SON that 6B4 phosphacan/RPTPbeta-immunoreactive
      perineuronal nets were seen around AVP-containing somata and dendrites and its
      distribution pattern was well coincided with that of TAG-1. Quantitative
      immunohistochemical and Western analyses showed that 1-week salt loading, known
      as the chronic physiological stimulation for inducing the structural changes such
      as synaptic remodeling and direct neuronal membrane apposition, decreased 6B4
      phosphacan/RPTPbeta levels in the SON, but did not alter TAG-1 levels. The 6B4
      phosphacan/RPTPbeta levels were returned to control basal values within 3 weeks
      after the cessation of the chronic stimulation. Activity-dependent decreases in
      6B4 phosphacan/RPTPbeta levels of the SON were confirmed when Western and
      immunohistochemical samples were digested with chondroitinase ABC, indicating
      that the decrease in 6B4 phosphacan/RPTPbeta levels was due to disappearance of
      6B4 phosphacan/RPTPbeta core protein rather than increase in chondroitin sulfate
      glycosaminoglycans. With electron microscopy, the electron-dense immunoproducts
      for 6B4 phosphacan/RPTPbeta were found on the membrane surface of axons and glial
      processes, but not at synaptic junctions in control SON, and its immunoreactivity
      was eliminated with the chronic salt loading. The present results indicate that
      the levels of 6B4 phosphacan/RPTPbeta are regulated with activity-dependent
      manner and may be concerned with the structural plasticity seen in the SON.

PMID- 15261113
TI  - Progressive plastic changes in the hand representation of the primary motor
      cortex parallel incomplete recovery from a unilateral section of the
      corticospinal tract at cervical level in monkeys.
AB  - After a sub-total hemisection of the cervical cord at level C7/C8 in monkeys, a
      paralysis of the homolateral hand is rapidly followed by an incomplete recovery
      of manual dexterity, reaching a plateau after about 40-50 days, whose extent
      appears related to the size of the lesion. During a few days after the lesion,
      the hand representation in the contralateral motor cortex disappeared, replaced
      by representations of either face or more proximal body parts. Later, however,
      following a time course (about 40 days) consistent with the functional recovery,
      progressive plastic changes in the contralateral motor cortex took place, as
      demonstrated by a progressive reappearance of digit movements elicited by
      intracortical microstimulation. These progressive plastic changes, which parallel
      the functional recovery, correspond to a reinstallation of a hand representation,
      though substantially diminished in size as compared to pre-lesion. Regarding the
      functional recovery, the motor cortex (including the reestablished hand area)
      contralateral to the unilateral cervical cord lesion played a crucial role in
      reestablishing control on finger movements, as assessed by reversible
      inactivation experiments. In contrast, the motor cortex ipsilateral to the
      cervical cord lesion, with largely intact projections to the spinal cord, did not
      contribute significantly to the recovered movements by the affected hand. These
      observations indicate that the CS fibers spared by the lesion are not sufficient,
      at least in their pre-lesion condition, to control the motoneurones innervating
      the digit muscles and that the pathways conveying signals from the contralateral
      M1 underwent reorganization.

PMID- 15261114
TI  - Functional re-establishment of the perforant pathway in organotypic co-cultures
      on microelectrode arrays.
AB  - Co-cultures of entorhinal cortex (EC) and dentate gyrus (DG) explants are a
      useful model system to study the formation and stabilization of axonal
      projections. We adapted this model system to EC-DG co-cultures on microelectrode
      arrays (MEA) for the characterization of axonal projections on a functional level
      for days and weeks. EC and DG explants were placed on MEA to allow for the
      reconstitution of perforant pathway projections. Connections formed were
      characterized by morphological and electrophysiological analyses to verify
      characteristic features of perforant pathway signal transmission. Morphological
      analysis reveals proper projection of EC neurons into the molecular layer of the
      DG. Examination of synaptic transmission after high frequency stimulation imply
      unidirectional connections that used glutamate receptors of the AMPA/kainate type
      as main mediators of excitatory signal transmission. The system was evaluated by
      the introduction of the NCAM binding peptide C3d. In accordance with in vivo and
      in vitro experiments C3d modulated signal transmission by NCAM-related mechanisms
      resulting in morphological re-arrangements.

PMID- 15261115
TI  - Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in
      the acutely dissociated hippocampus CA1 neurons.
AB  - The characterization of acid-sensing ion channel (ASIC)-like currents has been
      reported in hippocampal neurons in primary culture. However, it is suggested that
      the profile of expression of ASICs changes in culture. In this study, we
      investigated the properties of proton-activated current and its modulation by
      extracellular Ca(2+) and Zn(2+) in neurons acutely dissociated from the rat
      hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly
      decaying inward current and membrane depolarization was induced by exogenous
      application of acidic solution. The current was sensitive to the extracellular
      proton with a response threshold of pH 7.0-6.8 and the pH(50) of 6.1, the
      reversal potential close to the Na(+) equilibrium potential. It had a
      characteristic of acid-sensing ion channels (ASICs) as demonstrated by its
      sensitivity to amiloride (IC(50)=19.6+/-2.1 microM). Either low [Ca(2+)](o) or
      high [Zn(2+)](o) increased the amplitude of the current. All these
      characteristics are consistent with a current mediated through a mixture of
      homomeric ASIC1a and heteromeric ASIC1a+2a channels and closely replicate many of
      the characteristics that have been previously reported for hippocampal neurons
      cultured for a week or more, indicating that culture artifacts do not necessarily
      flaw the properties of ASICs. Interestingly, we found that high [Zn(2+)](o) (>10(
      4) M) slowed the decay time constant of the ASIC-like current significantly in
      both acutely dissociated and cultured hippocampal neurons. In addition, the
      facilitating effects of low [Ca(2+)](o) and high [Zn(2+)](o) on the ASIC-like
      current were not additive. Since tissue acidosis, extracellular Zn(2+) elevation
      and/or Ca(2+) reduction occur concurrently under some physiological and/or
      pathological conditions, the present observations suggest that hippocampal ASICs
      may offer a novel pharmacological target for therapeutic invention.

PMID- 15261116
TI  - Excitatory and inhibitory local circuit input to the rat dorsal motor nucleus of
      the vagus originating from the nucleus tractus solitarius.
AB  - The nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve
      (DMV) constitute sensory and motor nuclei of the dorsal vagal complex,
      respectively. We used whole-cell patch-clamp recordings from DMV neurons in rat
      brain slices and three methods of stimulation (electrical, glutamate microdrop,
      glutamate photostimulation) to test the hypothesis that convergent excitatory and
      inhibitory inputs to DMV neurons originate from intact neurons in multiple NTS
      areas. Electrical stimulation of the NTS resulted in evoked excitatory and
      inhibitory postsynaptic currents (eEPSCs and eIPSCs) in DMV neurons. Stimulation
      of the dorsal NTS with glutamate microdrops, which selectively stimulates the
      soma and dendrites of intact neurons, resulted in 31% of DMV neurons receiving
      eEPSCs, 44% receiving eIPSCs, and 6% receiving convergent excitatory and
      inhibitory inputs. Glutamate photostimulation allowed selective activation of
      intact neurons in multiple, discrete areas of the NTS and resulted in 36% of DMV
      neurons receiving eEPSCs, 65% receiving eIPSCs and 20% receiving both inputs.
      Data obtained by stimulation of multiple NTS areas support the hypothesis that
      there are anatomically convergent inputs to DMV neurons originating from intact
      neurons within the NTS. These data support the hypothesis that there is transfer
      of convergent information from the NTS to the DMV, implying that significant
      sensory-motor processing occurs within the brainstem.

PMID- 15261117
TI  - Involvement of L-type Ca2+ channels in the induction of long-term potentiation in
      the basolateral amygdala-dentate gyrus pathway of anesthetized rats.
AB  - We have recently found that synaptic pathway from the basolateral amygdala (BLA)
      to the dentate gyrus (DG) displays N-methyl-D-aspartate (NMDA) receptor
      independent form of long-term potentiation (LTP), which should be a valuable
      model for elucidating neural mechanisms linking emotion and memory. To explore
      its cellular mechanisms, we investigated the effects of L-type Ca(2+) channel
      blockers on LTP in this pathway of anesthetized rats. Intraperitoneal
      administration of verapamil (3-30 mg/kg) or diltiazem (6-20 mg/kg) significantly
      impaired the induction of LTP following high-frequency stimulation. When
      verapamil was administered after high-frequency stimulation, it did not affect
      the pre-established LTP. These results suggest that activation of L-type Ca(2+)
      channels is necessary for the induction of LTP in the BLA-DG pathway.

PMID- 15261118
TI  - Identification and cellular localisation of NPW1 (GPR7) receptors for the novel
      neuropeptide W-23 by [125I]-NPW radioligand binding and immunocytochemistry.
AB  - Using a novel radioligand, we have identified high-affinity binding sites
      (K(D)=0.44+/-0.13 nM) for the recently discovered peptide, neuropeptide W (NPW),
      in rat brain. Binding density was highest in the amygdala (B(max)=149.9+/-13.8
      fmol/mg protein), thalamic, and hypothalamic nuclei. A similar distribution was
      observed in mouse brain. We have confirmed the identity of these binding sites as
      the G-protein-coupled receptor, NPW(1) (previously designated orphan receptor
      GPR7), using site-directed antisera that revealed receptors were expressed by
      neuronal cell bodies and processes. Additionally, we have demonstrated the
      presence of NPW-like immunoreactivity in neuronal cell bodies in areas projecting
      to the amygdala, such as the dorsal raphe nucleus and ventral tegmental area,
      providing evidence for an emerging new transmitter system.

PMID- 15261119
TI  - Nicotinic modulation of area postrema neuronal excitability in rat brain slices.
AB  - We investigated the functions of nicotinic receptor activation on area postrema
      neurons by making whole-cell recordings in rat brainstem slices. Excitatory
      responses to nicotine application were found in approximately 78% (35/45) of all
      cells tested. Responsive cells included both the cells that display the
      hyperpolarization-activated cation current (I(h)) and cells that do not display
      I(h). An inhibitory effect of nicotine was never seen. Current-clamp recordings
      showed the nicotine-induced depolarization of a cell's membrane potential that
      could be sufficient to cause spontaneous firing. In voltage-clamp recordings,
      many cells showed nicotine-induced inward currents (18.3+/-3.2 pA, n=6) that
      persisted during pharmacological blockade of synaptic transmission (e.g., zero
      [Ca(2+)](out) and 5 mM [Mg(2+)](out), n=6/8). Other two cells, however, showed
      increases in the frequency of excitatory postsynaptic currents (EPSCs), which
      were blocked by CNQX (n=2/8). We analyzed miniature EPSCs (mEPSCs) recorded from
      cells that showed no inward currents but marked increases in the frequency of
      mEPSCs (0.8+/-0.2 to 4.8+/-1.7 Hz, n=4) during nicotine application. Nicotine
      augmented mEPSC amplitude (n=4); however, amplitude distribution was not
      significantly changed in two of four cells tested. We conclude that nicotinic
      receptors in the rat area postrema can excite cells via (1) a direct post- and/or
      extrasynaptic mechanism; and (2) an indirect enhancement of glutamate release.

PMID- 15261120
TI  - CRF1 receptor antagonist CP-154,526 reduces cardiovascular responses during acute
      psychological stress in rabbits.
AB  - We examined the effect of CP-154,526 on cardiovascular changes elicited in
      conscious rabbits by stressful stimuli (loud sound, cage move, pinprick,
      formaldehyde vapour and air-jet stress). CP-154,526 substantially reduced pressor
      and heart rate responses to these stimuli (both vagally and sympathetically
      mediated), and reduced QT shortening during air-jet stress. Blocking of central
      CRF1 receptors attenuates cardiovascular responses to environmental stimuli,
      presumably by affecting brain centres that control cardiovascular functions.

PMID- 15261121
TI  - Induction of activated caspase-3-immunoreactivity and apoptosis in the trigeminal
      ganglion neurons by neonatal peripheral nerve injury.
AB  - Immunohistochemistry for activated caspase-3 and terminal deoxynucleotidyl
      transferease-mediated dUTP-biotin nick end labeling (TUNEL) was performed on the
      trigeminal ganglion after infraorbital nerve transection in newborn rats. The
      injury induced caspase-3-immunoreactivity and DNA fragmentation in neuronal cell
      bodies in the maxillary division of the ganglion ipsilateral to the injury.
      Starting at 16 h post-injury the immunoreactive and TUNEL-positive neurons
      increased and reached the peak at 24 h (7.9% and 8.9%, respectively). Thereafter
      they decreased and returned to the normal control level (<<1%) by 72 h. A double
      staining procedure revealed coexpression of caspase-3-immunoreactivity and DNA
      fragmentation. 75.5% (114/151) of TUNEL-positive neurons expressed the
      immunoreactivity, while 84.4% (114/135) of immunoreactive neurons exhibited DNA
      fragmentation signal. These results suggest that caspase-3 plays an important
      role in apoptotic elimination of neonatally axotomized rodent primary neurons.

PMID- 15261122
TI  - Neurocalcin-immunoreactive neurons in the petrosal ganglion innervate the taste
      bud.
AB  - The distribution and origin of neurocalcin-immunoreactive (NC-ir) nerve fibers in
      the taste bud and carotid body were examined by an immunofluorescence method. In
      the circumvallate papilla of the tongue, NC-ir nerve fibers made subepithelial
      nerve plexuses and occasionally penetrated the taste bud. However, the carotid
      body was devoid of ir nerve fibers. In the petrosal ganglion, 32% of neurons were
      immunoreactive for NC. Such neurons were mostly medium-sized to large, and
      scattered throughout the ganglion. In the superior cervical and intralingual
      ganglia, numerous ir varicose fibers surrounded postsynaptic neurons. However, NC
      ir could not be detected in cell bodies of these neurons. The retrograde tracing
      method indicated that NC-ir petrosal neurons innervated taste buds in the
      circumvallate papilla. NC-ir neurons may have a gustatory function in the
      petrosal ganglion.

PMID- 15261124
TI  - Should simultaneous exercise become the standard for adenosine myocardial
      perfusion imaging?
AB  - Concomitant low-level treadmill exercise with adenosine pharmacologic stress
      (AdenoEx) during radionuclide myocardial perfusion imaging has become commonly
      used in recent years, particularly in large-volume laboratories. A number of
      studies have demonstrated a beneficial impact of AdenoEx protocols. These
      benefits include decreased side effects, improved safety and patient tolerance,
      improved target-to-background ratios because of less subdiaphragmatic activity,
      and improved sensitivity and defect reversibility. In light of these benefits,
      recent reviews and guidelines call for the addition of low-level exercise to
      adenosine stress whenever possible.

PMID- 15261126
TI  - Advances in myocardial contrast echocardiography and the role of adenosine
      stress.
AB  - Advances in contrast echocardiography hold promise for the routine assessment of
      myocardial perfusion. Continued progress may ultimately position myocardial
      contrast echocardiography (MCE) as an imaging modality that can provide
      comprehensive cardiac assessment-anatomic, physiologic, and pathophysiologic.
      Vasodilator stress with adenosine can play an important role in conjunction with
      MCE, particularly as it relates to the noninvasive evaluation of myocardial
      perfusion and coronary blood flow reserve. Adenosine pharmacologic stress testing
      may provide improved test performance through perfusion detection when compared
      with traditional use of dobutamine assessments of regional wall motion
      abnormalities.

PMID- 15261128
TI  - Cardiac positron emission tomography and the role of adenosine pharmacologic
      stress.
AB  - Although single-photon emission computed tomography (SPECT) provides excellent
      diagnostic and prognostic value in the evaluation of coronary artery disease, its
      progress has slowed relative to emerging modalities, such as cardiac positron
      emission tomography (PET). PET imaging provides certain advantages versus SPECT,
      including higher spatial resolution, improved attenuation correction, and the
      capability to perform quantitative measurements at the peak of stress. Cardiac
      PET scanning is a well-validated, reimbursable means to noninvasively assess
      myocardial perfusion, left ventricular function, and viability by dynamically
      imaging positron-labeled radiopharmaceuticals in vivo. For the stress portion of
      rubidium-82 (Rb-82) PET protocols, pharmacologic agents are commonly used because
      of the short half-life of Rb-82. In light of recent advances in cardiac PET
      equipment, the expansion of PET/computed tomography scanners, and the resulting
      potential for streamlined protocols, adenosine may become widely used in
      electrocardiographic-gated rest-stress acquisition protocols with Rb-82 cardiac
      PET. With the resolution of technical issues, cardiac PET has an opportunity to
      become the standard for evaluation of myocardial perfusion in the coming years.

PMID- 15261130
TI  - Cardiovascular magnetic resonance and the role of adenosine pharmacologic stress.
AB  - As an advanced imaging modality, cardiovascular magnetic resonance (CMR) offers
      high spatial resolution and produces unsurpassed images of the heart and its
      function. Clinically, CMR is well established in the assessment of congenital
      heart disease, the aorta, tumors, the pericardium, cardiac mass and function,
      flow measurement, and the structure and function of the right ventricle. CMR has
      demonstrated a high interstudy reproducibility of left ventricular volumes,
      ejection fraction, and mass, making it the ideal noninvasive technique for serial
      measurements. CMR growth areas that are nearing routine clinical application are
      the evaluation of myocardial perfusion, infarction, and viability. In perfusion
      CMR studies, pharmacologic stress is used to increase differences in the first
      pass delivery of the contrast agent between myocardial regions perfused by normal
      and diseased arteries. The most widely used stress modality for CMR perfusion
      studies is adenosine.

PMID- 15261132
TI  - The future of pharmacologic stress: selective A2A adenosine receptor agonists.
AB  - Adenosine and dipyridamole, the currently available vasodilators for myocardial
      perfusion imaging, produce hyperemic coronary flow by stimulating A(2A) adenosine
      receptors on arteriolar vascular smooth muscle cells. However, both vasodilators
      nonselectively activate A(1), A(2B), and A(3) adenosine receptors, which
      contributes to common undesirable effects. In the development of a novel
      pharmacologic stress agent, more selective agonism of the A(2A) receptor subtype
      would be desirable. Currently, 2 selective A(2A) adenosine receptor agonists are
      being evaluated in phase 3 studies as pharmacologic stress agents. The highly
      selective, potent, low-affinity A(2A) adenosine agonist regadenoson (also known
      as CVT-3146) holds significant potential as a pharmacologic stress agent, based
      on available results from experimental and clinical trials. Regadenoson produces
      maximal hyperemia quickly and maintains it for an optimal duration that is
      practical for radionuclide myocardial perfusion imaging. Regadenoson's simple
      rapid bolus administration and short duration of hyperemic effect point to an
      advantage of enhanced control for the clinician.

PMID- 15261134
TI  - Homeostasis in the breast: it takes a village.
AB  - Progression from normal to malignant phenotype involves aberrations in the
      reciprocal interactions of multiple cell types with each other and with other
      components of the microenvironment. In this issue of Cancer Cell, demonstrate
      that progression to breast cancer involves genotypic as well as gene expression
      changes that are cell type-specific, suggesting that targeted therapies delivered
      to the tumor may need to include drugs targeted not only to the tumor cells, but
      also to the other cell types in the tumor microenvironment.

PMID- 15261135
TI  - p53--an examination of sibling support in apoptosis control.
AB  - While p53 family members have distinct nonoverlapping functions, the involvement
      of p63 and p73 in p53-mediated apoptosis is controversial. Results of a recent
      study indicate that at least in thymocytes, p53-dependent apoptosis occurs
      independently of p63 and p73.

PMID- 15261136
TI  - Met decoys: will cancer take the bait?
AB  - Inappropriate Met receptor tyrosine kinase signaling can produce proliferative,
      invasive, angiogenic, and antiapoptotic activities that contribute to malignant
      growth. Met can be activated by paracrine or autocrine mechanisms in a ligand
      dependent fashion, or be constitutively activated by mutation and by other ligand
      independent mechanisms. Because Met is inappropriately expressed in almost all
      types of human cancer, the HGF/SF-Met signaling pathway should be an exceptional
      target for cancer intervention strategies and therapies. In this issue of Cancer
      Cell, two reports show that the extracellular domain of Met is an important
      target for developing anticancer therapies.

PMID- 15261137
TI  - Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma
      syndromes.
AB  - The LKB1 tumor suppressor protein controls the activity of the TSC1/TSC2 tumor
      suppressor complex. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), and
      mutations in either TSC1 or TSC2 cause tuberous sclerosis complex--two syndromes
      characterized by the development of hamartomas. LKB1 activation by energy
      deprivation activates AMPK, which in turn phosphorylates and activates TSC2. TSC2
      activation results in the inactivation of mTOR, a critical regulator of protein
      translation. How mTOR dysregulation after inactivation of LKB1 or TSC1/2
      contributes to hamartoma development is not known. However, hypoxia-inducible
      factor (HIF) and VEGF are regulated by mTOR and are likely to play a contributory
      role.

PMID- 15261138
TI  - Focus on Barrett's esophagus and esophageal adenocarcinoma.

PMID- 15261139
TI  - Molecular characterization of the tumor microenvironment in breast cancer.
AB  - Here we describe the comprehensive gene expression profiles of each cell type
      composing normal breast tissue and in situ and invasive breast carcinomas using
      serial analysis of gene expression. Based on these data, we determined that
      extensive gene expression changes occur in all cell types during cancer
      progression and that a significant fraction of altered genes encode secreted
      proteins and receptors. Despite the dramatic gene expression changes in all cell
      types, genetic alterations were detected only in cancer epithelial cells. The
      CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and
      myofibroblasts, respectively, bind to receptors on epithelial cells and enhance
      their proliferation, migration, and invasion. Thus, chemokines may play a role in
      breast tumorigenesis by acting as paracrine factors.

PMID- 15261140
TI  - Small molecule blockade of transcriptional coactivation of the hypoxia-inducible
      factor pathway.
AB  - Homeostasis under hypoxic conditions is maintained through a coordinated
      transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway
      and requires coactivation by the CBP and p300 transcriptional coactivators.
      Through a target-based high-throughput screen, we identified chetomin as a
      disrupter of HIF binding to p300. At a molecular level, chetomin disrupts the
      structure of the CH1 domain of p300 and precludes its interaction with HIF,
      thereby attenuating hypoxia-inducible transcription. Systemic administration of
      chetomin inhibited hypoxia-inducible transcription within tumors and inhibited
      tumor growth. These results demonstrate a therapeutic window for pharmacological
      attenuation of HIF activity and further establish the feasibility of disrupting a
      signal transduction pathway by targeting the function of a transcriptional
      coactivator with a small molecule.

PMID- 15261141
TI  - Chk1 is haploinsufficient for multiple functions critical to tumor suppression.
AB  - The haploinsufficient tumor suppressor Chk1 is essential for embryonic cells, but
      the consequences of Chk1 loss in adult tissues are unknown. Using conditional
      Chk1 mice, we find that proliferating mammary cells lacking Chk1 undergo
      apoptosis leading to developmental defects. Conditional Chk1 heterozygosity
      increased the number of S phase cells and caused spontaneous DNA damage. Chk1+/-
      epithelia also exhibit a miscoordinated cell cycle in which S phase cells display
      an early mitotic phenotype. These cells maintain high levels of Cdc25A, which can
      promote inappropriate cell cycle transitions. Thus, Chk1 heterozygosity results
      in three distinct haploinsufficient phenotypes that can contribute to
      tumorigenesis: inappropriate S phase entry, accumulation of DNA damage during
      replication, and failure to restrain mitotic entry.

PMID- 15261142
TI  - Targeting the tumor and its microenvironment by a dual-function decoy Met
      receptor.
AB  - Met, the receptor for hepatocyte growth factor (HGF), is activated in human
      cancer by both ligand-dependent and -independent mechanisms. We engineered a
      soluble Met receptor (decoy Met) that interferes with both HGF binding to Met and
      Met homodimerization. By lentiviral vector technology, we achieved local or
      systemic delivery of decoy Met in mice. We provide evidence that in vivo
      expression of decoy Met (1) inhibits tumor cell proliferation and survival in a
      variety of human xenografts, (2) impairs tumor angiogenesis by preventing host
      vessel arborization, (3) suppresses or prevents the formation of spontaneous
      metastases, and (4) synergizes with radiotherapy in inducing tumor regression,
      without (5) affecting housekeeping physiological functions in the adult animal.

PMID- 15261143
TI  - The Sema domain of Met is necessary for receptor dimerization and activation.
AB  - Hepatocyte growth factor (HGF) binds the extracellular domain and activates the
      Met receptor to induce mitogenesis, morphogenesis, and motility. The
      extracellular domain of Met is comprised of Sema, PSI, and four IPT subdomains.
      We investigated the contribution of these subdomains to Met receptor
      dimerization. Our observations indicate that the Sema domain is necessary for
      dimerization in addition to HGF binding. Treatment of Met-overexpressing tumor
      cells with recombinant Sema in the presence or absence of HGF results in
      decreased Met-mediated signal transduction, cell motility, and migration,
      behaving in a manner similar to an antagonistic anti-Met Fab. These data suggest
      that the Sema domain of Met may not only represent a novel anticancer therapeutic
      target but also acts as a biotherapeutic itself.

PMID- 15261144
TI  - p63 and p73 are not required for the development and p53-dependent apoptosis of T
      cells.
AB  - The recent discoveries of p63 and p73, homologs of the tumor suppressor p53,
      raised the possibility of a network of these family members governing cell cycle
      arrest and apoptosis in response to stress. However, mice lacking p73 show no
      tendency for spontaneous tumors, and mutations in p63 or p73 are rare in human
      tumors, rendering any obligate role of these genes in cell death and tumor
      suppression unclear. In an effort to reconcile these incongruent data, we
      examined the genetic interactions between p53, p63, and p73 in well-established
      paradigms of p53-dependent and -independent T cell death using primary,
      genetically defined lymphocytes. Our findings challenge the generality of the
      notion that p63 and p73 are required for p53 function or for apoptosis in T
      cells.

PMID- 15261145
TI  - The LKB1 tumor suppressor negatively regulates mTOR signaling.
AB  - Germline mutations in LKB1, TSC2, or PTEN tumor suppressor genes result in
      hamartomatous syndromes with shared tumor biological features. The recent
      observations of LKB1-mediated activation of AMP-activated protein kinase (AMPK)
      and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical
      and biological relationship between LKB1 and mTOR regulation. Here, we report
      that LKB1 is required for repression of mTOR under low ATP conditions in cultured
      cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the
      hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated
      signaling downstream of mTOR. These findings position aberrant mTOR activation at
      the nexus of these germline neoplastic conditions and suggest the use of mTOR
      inhibitors in the treatment of Peutz-Jeghers syndrome.

PMID- 15261146
TI  - Measuring quality of research: what do they mean and why they mean so?

PMID- 15261147
TI  - Stochastic approaches for modelling in vivo reactions.
AB  - In recent years, stochastic modelling has emerged as a physically more realistic
      alternative for modelling in vivo reactions. There are numerous stochastic
      approaches available in the literature; most of these assume that observed random
      fluctuations are a consequence of the small number of reacting molecules. We
      review some important developments of the stochastic approach and consider its
      suitability for modelling intracellular reactions. We then describe recent
      efforts to include the fluctuation effects caused by the structural organisation
      of the cytoplasm and the limited diffusion of molecules due to macromolecular
      crowding.

PMID- 15261148
TI  - Homology modeling and molecular dynamics study of GSK3/SHAGGY-like kinase.
AB  - Although the GSK3/SHAGGY-like kinase is a highly conserved serine/threonine
      kinase implicated in many signaling pathways in eukaryotes, the lack of knowledge
      of its three-dimensional (3D) structure has hindered efforts to understand the
      binding specificities of substrate and catalytic mechanism. To understand the
      structure-activity relationships, the protein 3D structure was built by using
      homology modeling based on the known X-ray diffraction structure of Glycogen
      synthase kinase-3beta (Gsk3beta) and the model structure was further refined
      using unrestrained molecular dynamics simulations. The research indicates that
      the general 3D organization of the GSK3/SHAGGY-like kinase is a typical kinase
      family and comprises an N-terminal domain of beta-sheet and a larger C-terminal
      domain mainly constituted by alpha-helix. In order to understand the molecular
      interactions between the natural substrate-ATP and GSK3/SHAGGY-like kinase, a 3D
      model of the complex ATP-GSK3/SHAGGY-like kinase is developed by molecular
      docking program, which is helpful to guide the experimental realization and the
      new mutant designs as well. One important finding is that the identification of
      the key binding-site residue of Lys69 which plays an important role in the
      catalysis of GSK3/SHAGGY-like kinase and this is in consistent with experimental
      observation.

PMID- 15261149
TI  - Scoring hidden Markov models to discriminate beta-barrel membrane proteins.
AB  - A new method is presented for identification of beta-barrel membrane proteins. It
      is based on a hidden Markov model (HMM) with an architecture obeying these
      proteins' construction principles. Once the HMM is trained, log-odds score
      relative to a null model is used to discriminate beta-barrel membrane proteins
      from other proteins. The method achieves only 10% false positive and false
      negative rates in a six-fold cross-validation procedure. The results compare
      favorably with existing methods. This method is proposed to be a valuable tool to
      quickly scan proteomes of entirely sequenced organisms for beta-barrel membrane
      proteins.

PMID- 15261150
TI  - Principles of rapid polymerase chain reactions: mathematical modeling and
      experimental verification.
AB  - Polymerase chain reaction (PCR) is an important diagnostic tool for the
      amplification of DNA. The PCR process can be treated as a problem in biochemical
      engineering. This study focuses on the development of a mathematical model of the
      polymerase chain reaction. The PCR process consists of three steps: denaturation
      of target DNA, annealing of sequence-specific oligonucleotide primers and the
      enzyme-catalyzed elongation of the annealed complex (primer:DNA:polymerase). The
      denaturation step separates the double strands of DNA; this model assumes
      denaturation is complete. The annealing step describes the formation of a primer
      fragment complex followed by the attachment of the polymerase to form a ternary
      complex. This step is complicated by competitive annealing between primers and
      incomplete fragments including primer-primer reactions. The elongation step is
      modeled by a stochastic method. Species that compete during the elongation step
      are deoxynucleotide triphosphates dCTP, dATP, dTTP, dGTP, dUTP, and
      pyrophosphate. Thermal deamination of dCTP to form dUTP is included in the model.
      The probability for a species to arrive at the active site is based on its molar
      fraction. The number of random insertion events depends on the average processing
      speed of the polymerase and the elongation time of the simulation. The numerical
      stochastic experiment is repeated a sufficient number of times to construct a
      probability density distribution (PDF). The moment of the PDF and the annealing
      step products provide the product distribution at the end of the elongation step.
      The overall yield is compared to six experimental values of the yield. In all
      cases the comparisons are very good.

PMID- 15261151
TI  - Cluster-C, an algorithm for the large-scale clustering of protein sequences based
      on the extraction of maximal cliques.
AB  - Although the characterization of proteins cannot solely rely upon sequence
      similarity, it has been widely proved that all-vs-all massive sequence
      comparisons may be an effective approach and a good basis for the prediction of
      biochemical functions or for the delineation of common shared properties. The
      program Cluster-C presented here enables a stand-alone and efficient construction
      of protein families within whole proteomes. The algorithm, which is based on the
      detection of cliques, ensures a high level of connectivity within the clusters.
      As opposed to the single transitive linkage method, Cluster-C allows a large
      number of sequences to be classified in such a way that the multidomain proteins
      do not produce a chain-grouping effect resulting in meaningless clusters.
      Moreover, some proteins can be present in several different but relevant
      clusters, which is of help in the determination of their functional domains. In
      the present analysis we used the Z-value, an evaluation of the significance of
      the similarity score, as the criterion for connecting sequences (the user can
      freely define the threshold of the similarity criterion). The clusters built with
      a rather low threshold (Z= 14) include more than 97% of the sequences and are
      consistent with known protein families and PROSITE patterns.

PMID- 15261152
TI  - Evolutionary rate variation and RNA secondary structure prediction.
AB  - Predicting RNA secondary structure using evolutionary history can be carried out
      by using an alignment of related RNA sequences with conserved structure.
      Accurately determining evolutionary substitution rates for base pairs and single
      stranded nucleotides is a concern for methods based on this type of approach.
      Determining these rates can be hard to do reliably without a large and accurate
      initial alignment, which ideally also has structural annotation. Hence, one must
      often apply rates extracted from other RNA families with trusted alignments and
      structures. Here, we investigate this problem by applying rates derived from tRNA
      and rRNA to the prediction of the much more rapidly evolving 5'-region of HIV-1.
      We find that the HIV-1 prediction is in agreement with experimental data, even
      though the relative evolutionary rate between A and G is significantly increased,
      both in stem and loop regions. In addition we obtained an alignment of the 5' HIV
      1 region that is more consistent with the structure than that currently in the
      database. We added randomized noise to the original values of the rates to
      investigate the stability of predictions to rate matrix deviations. We find that
      changes within a fairly large range still produce reliable predictions and
      conclude that using rates from a limited set of RNA sequences is valid over a
      broader range of sequences.

PMID- 15261153
TI  - Cycling in ecological networks: Finn's index revisited.
AB  - A chief cybernetic feature of natural living systems is the recycling of
      nutrients, which tends to enhance stability and is one of the principal causes of
      ecosystem complexity. In 1976, Finn proposed a simple and effective measure
      (later known as the Finn cycling index [FCI]) to assess the quantitative
      importance of cycles in ecosystems. This index was successfully applied as a
      gauge of ecosystem health and maturity in a wide variety of studies. It turns
      out, however, that FCI is biased as a measure of cycling in ecosystems, because
      it does not include all flows engaged in recycling. A new, more inclusive version
      of the index is possible. What is called the comprehensive cycling index (CCI)
      accounts for all of the fluxes generated by cycling. Computing the new measure
      requires a large amount of time, however, even with ad-hoc software. To obviate
      the necessity for such heavy computation, a linear transformation of the FCI into
      the CCI is proposed.

PMID- 15261154
TI  - Multi-class tumor classification by discriminant partial least squares using
      microarray gene expression data and assessment of classification models.
AB  - High-throughput DNA microarray provides an effective approach to the monitoring
      of expression levels of thousands of genes in a sample simultaneously. One
      promising application of this technology is the molecular diagnostics of cancer,
      e.g. to distinguish normal tissue from tumor or to classify tumors into different
      types or subtypes. One problem arising from the use of microarray data is how to
      analyze the high-dimensional gene expression data, typically with thousands of
      variables (genes) and much fewer observations (samples). There is a need to
      develop reliable classification methods to make full use of microarray data and
      to evaluate accurately the predictive ability and reliability of such derived
      models. In this paper, discriminant partial least squares was used to classify
      the different types of human tumors using four microarray datasets and showed
      good prediction performance. Four different cross-validation procedures (leave
      one-out versus leave-half-out; incomplete versus full) were used to evaluate the
      classification model. Our results indicate that discriminant partial least
      squares using leave-half-out cross-validation provides a more realistic estimate
      of the predictive ability of a classification model, which may be overestimated
      by some of the cross-validation procedures, and the information obtained from
      different cross-validation procedures can be used to evaluate the reliability of
      the classification model.

PMID- 15261155
TI  - Presence and localization of epidermal growth factor (EGF)- and EGF-receptor-like
      immunoreactivity in Tetrahymena.
AB  - The presence of EGF- and EGF-receptor-like immunoreactivity in Tetrahymena was
      studied with the help of FITC-labelled monoclonal antibodies, using flow
      cytometry and confocal microscopy. Tetrahymena has endogeneous EGF and treatment
      with it significantly increases the hormone content of the cells. The hormone is
      diffusely localized, particularly in the cytopharynx, where it forms a structure
      larger than 10 microm. EGF-receptors are also demonstrable, particularly in the
      cortical region in connection with cilia, and EGF treatment significantly
      enhances cortical fluorescence. The relationships between these observations and
      literary data on the effects of EGF in Tetrahymena are discussed.

PMID- 15261156
TI  - The comet assay differentiates efficiently and rapidly between genotoxins and
      cytotoxins in quiescent cells.
AB  - Our main aim was to establish the efficiency of the single cell electrophoresis
      technique for differentiating between drugs that bind DNA and those that do not.
      The alkaline comet assay was used to test the responses of human leukocytes
      (quiescent cells) to damage induced by reportedly genotoxic and reportedly
      cytotoxic agents. Incubation of G0 leukocytes for 1 h with the genotoxic agents
      camptothecin and actinomycin C provoked DNA migration, observed as comet figures.
      On the other hand, when cells were treated with the cytotoxic agents cordycepin,
      fluorodeoxyuridine and puromycin, the leukocyte nuclei were indistinguishable
      from those of untreated cells. In addition, we have developed a rapid method
      using non-proliferating cells that requires neither culture nor lymphocyte
      isolation. This method promises to be useful as a rapid in vitro screening assay.

PMID- 15261157
TI  - Cell division induced by mechanical stimulation in starved Tetrahymena
      thermophila: cell cycle without synthesis of macronuclear DNA.
AB  - Starved Tetrahymena thermophila cells underwent synchronous cell division 2 h
      after a mechanical stimulation. The macronucleus showed no obvious increase in
      DNA content before the cell division in the starvation medium, and the DNA
      content was decreased after the cell division. On the other hand, when the
      starved cells were given nutrient-supplied medium immediately after the
      mechanical stimulation, cell division was delayed for 3 h. This period was almost
      the same as that for G1 cells in the stationary culture to first division after
      transfer to fresh nutrient medium. These results suggest that the mechanical
      stimulation induces an early division of starved cells, skipping the macronuclear
      S-phase with the starved cells probably becoming trapped in G1. Starved cells
      that had finished division soon formed mating pairs with cells of the opposite
      type. These observations lead us to propose that cell division in starvation
      conditions may be necessary to reduce macronuclear DNA content prior to the
      mating of T. thermophila.

PMID- 15261158
TI  - Unpolymerized nuclear actin is involved in the activation of CSF-1 gene
      transcription.
AB  - Nuclear actin is a nuclear component in many kinds of eukaryotic cells but its
      function is still not clear. In this study, we overexpressed actin in nuclei and
      found that it promoted transcription of the CSF-1 gene, both exogenous and
      endogenous, approximately two-fold. Cytochalasin B did not affect this function
      of nuclear actin. Our results suggest that nuclear actin plays a role in
      regulating CSF-1 gene transcription, and this role does not depend on actin
      polymerization.

PMID- 15261159
TI  - Effect of stress-induced lipid peroxidation on functions of rat peritoneal
      macrophages.
AB  - The aim of the present study was to investigate the effects of stress-induced
      lipid peroxidation on macrophages' functions. Animals were subjected to 4 h
      immobilization at 4 degrees C in restraining devices. The peritoneal macrophages
      obtained from rats exposed to cold and restraint stress exhibited an increase in
      lipid peroxidation and a decline of chemotaxis and phagocytosis compared with
      control rats. After supplementation with vitamin E, the increment in
      thiobarbituric acid reactive substances (TBARS) content as the oxidative stress
      marker and the decline of chemotaxis and phagocytosis in peritoneal macrophages
      observed during cold-restraint stress was significantly removed. No significant
      change in catalase activity of peritoneal macrophages was observed in groups
      exposed to cold-restraint stress and treated with vitamin E. These findings
      indicate that phagocytic and chemotactic capacities of peritoneal macrophages are
      decreased by cold-restraint stress and this effect of stress may be related to
      lipid peroxidation.

PMID- 15261160
TI  - Enrichment and characterization of mouse putative epidermal stem cells.
AB  - Epidermis, a continuously renewing tissue, is maintained by stem cells that
      proliferate and replenish worn out or damaged cells in the tissue during life.
      Cultured epidermal stem cells have great potential in scientific research and
      clinical application. However, isolating a pure and viable population of
      epidermal stem cells and culturing them has been challenging. In this study,
      putative epidermal stem cells of mouse were isolated by combining Hoechst 33342
      and propidium iodide staining with fluorescence-activated cell sorting. Molecular
      markers expression pattern analysis showed that cytokeratin 14, integrin beta1
      and p63 are expressed in the sorted putative stem cells, but not active beta
      catenin, nestin and involucrin. Our results provide further supporting data that
      mouse putative epidermal stem cells could be successfully isolated by combining
      Hoechst dye staining with fluorescence-activated cell sorting and cultured in
      vitro. The cultured mouse putative epidermal stem cells could be used as a potent
      tool for studying stem cell biology and testing stem cell therapy.

PMID- 15261161
TI  - Cytotoxicity of tamoxifen in normal and tumoral cell lines and its ability to
      induce cellular transformation in vitro.
AB  - Tamoxifen (TAM) is a non-steroidal anti-estrogen used to treat patients with
      estrogen receptor-positive breast cancer and as a chemopreventive agent against
      breast cancer in high risk pre- and post-menopausal women. However, recent
      studies have shown that tamoxifen causes endometrial and hepatic cancer. In this
      study, we examined the effects of tamoxifen (5, 10, 25 and 50 microM) on the
      growth and proliferation of nine tumoral cell lines (UACC62, MCF-7, NCI-460, K
      562, OVCAR-03, PC-03, HT-29, 786-0, NCI-ADR) and non-tumoral cell lines (3T3,
      V79, MDCK, VERO). Chinese hamster lung fibroblasts (V79) were the most sensitive
      lineage to tamoxifen, with 21.6% of the cells showing apoptosis at 50 microM TAM.
      Microscopic analysis showed that, the cellular transformation caused by TAM in
      V79 cells was similar to that seen with 7,12-dimethylbenz(a)anthracene, thus
      indicating the carcinogenicity of TAM.

PMID- 15261162
TI  - An in vitro model to evaluate cell adhesion to metals used in implantation shows
      significant differences between palladium and gold or platinum.
AB  - Adhesion of tissue cells to metallic implants is a major factor that is important
      for proper tissue integration. Adhesion of Swiss mouse 3T3 fibroblasts to gold,
      platinum and palladium surfaces was investigated. Immunofluorescence staining for
      the integrin subunits alphav and beta1 and the focal contact protein vinculin
      revealed that cells growing on gold and platinum expressed many focal contacts.
      In contrast, cells on palladium surfaces had reduced numbers of focal contacts
      shown by vinculin staining and failed to demonstrate expression of alphav and
      beta1 in focal contacts. Spread cell area was also significantly reduced on
      palladium than on other surfaces suggesting that cells on palladium were more
      weakly attached. This may be due to either a different molecular composition of
      focal contacts in cells grown on palladium surfaces or unusual microstructural
      properties of the palladium surface. This model is useful to evaluate adhesion of
      cells to different metal surfaces.

PMID- 15261163
TI  - Altered cyclic expression of epithelial Na+ channel subunits and cystic fibrosis
      transmembrane conductance regulator in mouse endometrium by a low sodium diet.
AB  - Epithelial Na+ channel (ENaC) and cystic fibrosis transmembrane conductance
      (CFTR) have been shown to exhibit cyclic expression patterns in the uterus and
      demonstrated to play important roles in regulating uterine fluid absorption and
      secretion. The present study investigated the effect of a low Na+ diet on the
      cyclic expression of uterine ENaC subunits and CFTR in mice. Ten to 12 weeks old
      ICR mice with synchronized estrus cycle were fed with a low sodium diet for at
      least 2 weeks and the mRNA level of these ion channels was examined by semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). Functional
      channel activities in primary cultures of endometrial epithelia were assessed by
      the short-circuit current (Isc) technique. The characteristic cyclic expression
      of ENaC subunits throughout the estrus cycle remained unchanged but their
      expression levels towards the diestrus stage were drastically elevated. The
      cyclic expression pattern of CFTR was disrupted with suppressed expression
      throughout the cycle. Isc measurements showed that treatment of cultured
      endometrial epithelial cells with aldosterone, the major hormone expected to be
      elevated during the low sodium diet, resulted in prominent increase in ENaC
      channel activity. The altered cyclic expression of uterine ENaC and CFTR by a low
      sodium diet suggests that these ion channels may be affected by elevated
      circulating aldosterone, which may disrupt reproductive events in the uterus.

PMID- 15261164
TI  - 2,4,5-T and 2,4,5-TCP induce oxidative damage in human erythrocytes: the role of
      glutathione.
AB  - The molecular basis of the toxic properties of phenoxy herbicides in humans and
      animals has been insufficiently studied. In this study, damage parameters [levels
      of reduced glutathione (GSH) and total glutathione; activity of glutathione
      reductase (GR); activities of catalase (CAT) and superoxide dismutase (SOD);
      levels of adenine nucleotides and adenine energy charge (AEC)] were measured in
      human erythrocytes exposed in vitro to 2,4,5-trichlorophenoxyacetic acid (2,4,5
      T) and its metabolite 2,4,5-trichlorophenol (2,4,5-TCP). Both 2,4,5-T and 2,4,5
      TCP decreased the level of reduced glutathione (GSH) in erythrocytes in
      comparison to the control, but did not significantly change the total glutathione
      (2GSH + GSSG). This suggests that GSH concentration decreases concomitantly with
      an increase in oxidized glutathione (GSSG). 2,4,5-TCP at 100 ppm significantly
      decreased catalase and SOD activities. 2,4,5-T and 2,4,5-TCP did not
      significantly change the activity of glutathione reductase. 2,4,5-TCP decreased
      the level of ATP and increased the content of ADP and AMP, indicating a fall in
      AEC. 2,4,5-T and 2,4,5-TCP significantly changed the erythrocyte morphology. All
      these data are evidence of oxidative stress in erythrocytes incubated with 2,4,5
      T and 2,4,5-TCP; the stress appears to be more intense in the case of 2,4,5-TCP.

PMID- 15261165
TI  - Carbon dioxide laser resurfacing.
AB  - The carbon dioxide laser has become the gold standard for resurfacing because of
      its predictability, safety, and efficacy. Careful patient selection, well-planned
      preoperative regimens, attention to technique, and close postoperative care all
      contribute to better outcomes. These points as well as possible complications and
      their treatment are reviewed.

PMID- 15261166
TI  - Medium depth peels.
AB  - Medium depth chemical peels offer an excellent tool for skin rejuvenation. The
      improvement in rhytids, dyschromias, and photodamage with relatively little
      downtime confirms its importance in the facial plastic armamentarium.

PMID- 15261167
TI  - Review of nonablative laser resurfacing modalities.
AB  - Because of considerable morbidities and recovery time associated with CO2 laser
      resurfacing,many efforts are being made to discover a less ablative resurfacing
      modality. A thorough review of the literature demonstrates promising but less
      than ideal results for all of the currently used lasers. The clinical efficacy
      does not appear to be as significant as the histologic results that have been
      documented. Our review of the literature also demonstrates that not all of the
      modalities are equal.

PMID- 15261168
TI  - Superficial skin resurfacing.
AB  - Options for both the cosmetic surgeon offering and patients seeking treatment for
      cutaneous aging have expanded greatly in recent years and continue to grow.
      Increasingly sophisticated aesthetic patients are seeking procedures to
      rejuvenate in record numbers,but many are unwilling to tolerate a large amount of
      downtime. In expert hands, ablative laser resurfacing has a long history of
      dramatic results for the treatment of cutaneous aging. During the last decade,
      there have been a growing number of reports of modalities targeting the more
      superficial skin structure. Such modalities offer more modest results without the
      downtime associated with more aggressively ablative procedures. These resurfacing
      techniques include the use of mechanical, chemical, and thermal forces.

PMID- 15261169
TI  - Use of combined modality for maximal resurfacing.
AB  - Resurfacing of the skin plays a substantial role in facial rejuvenation. To
      better prepare the cosmetic surgeon for this endeavor, we have set out to define
      aging skin changes,review resurfacing indications, outline and compare various
      resurfacing practices, and discuss anticipated outcomes in our experience and in
      the current literature. We have found that appropriate patient selection,
      counseling, and technique have yielded a consistent result with a high degree of
      patient satisfaction. Furthermore, outcomes are maximized when one takes
      advantage of multiple modalities, combining resurfacing techniques, or when one
      combines resurfacing with surgical rejuvenation.

PMID- 15261170
TI  - Radiofrequency nonablative tissue tightening.
AB  - Minimally invasive procedures have become an extremely important component of a
      facial cosmetic surgery practice. This article describes a new radiofrequency
      device that tightens soft tissue without ablating the skin. The net result of
      this is a noninvasive brow lift, facelift, or neck lift. This modality does not
      replace current surgical procedures but is an excellent complement to them and a
      treatment option for patients to consider. The author's experience with this
      device is discussed.

PMID- 15261171
TI  - Acne vulgaris.
AB  - Acne vulgaris is a common inflammatory skin condition that presents management
      difficulties to cosmetic surgeons. Acute management and treatment focuses on
      early diagnosis as well as treatment with topical agents, oral antibiotics,
      hormonal therapy,and nonablative chemical peel and laser applications. The
      treatment of postinflammatory scarring must be individualized to address
      potential macular dyschromia, cystic lesions,epithelial bridges, or deep pitted
      scars. A review of interventional options is presented to apply to the spectrum
      of acne scarring as well as a review of the literature to address objectively
      published reports on efficacy.

PMID- 15261172
TI  - Classifying, diagnosing, and treating the complications of resurfacing the facial
      skin.
AB  - Resurfacing describes a broad range of treatments meant to address visible signs
      of aging within the skin. This can be achieved by inducing damage in the
      epidermis, reticular dermis, or even into the papillary dermis. The body's
      ability to repair that damage is responsible for the result. Complications for a
      patient can be broadly categorized as infectious,cicatricial, pigmentary,
      inflammatory (prolonged erythema, contact dermatitis), and systemic. Each of
      these complications is examined with attention to diagnosis and treatment.

PMID- 15261173
TI  - Anti-aging products and cosmeceuticals.
AB  - Topical therapies can be used as a solo treatment or as an adjunct to the various
      surgical options to improve upon and maintain the desired anti-aging results.
      They may also be used as a preventative therapy in younger men and women. Few
      drugs are currently marketed for the treatment and prevention of skin aging,
      whereas many cosmeceuticals,the fastest growing segment of the skin-care market,
      and herbal remedies are touted in the lay press. More than ever, patients are
      looking for a magical elixir that is easy to use,effective, and inexpensive. The
      more commonly used products are covered in this article.

PMID- 15261174
TI  - Erbium:YAG laser skin resurfacing.
AB  - The Erbium:YAG laser is a useful flexible tool for the surgeon interested in
      providing overall skin rejuvenation. With its unique wavelength, greater
      absorption, and less thermal injury, it can offer more precise ablation with
      greater safety and shorter healing times. All skin types as well as all body
      parts can safely be treated, from simple lentigines to deeper rhytides. The
      Erbium:YAG laser is an effective tool for complete skin rejuvenation. System
      specifications and parameters are reviewed along with pathology,uses, and
      techniques including postoperative care, risks, and safety profile.

PMID- 15261176
TI  - Total artificial heart bridge to transplantation: a 9-year experience with 62
      patients.
AB  - BACKGROUND: The SynCardia CardioWest total artificial heart (CardioWest TAH) is a
      biventricular, orthotopic, pneumatic, pulsatile blood pump driven by an external
      console. For each ventricle, the length of the blood-flow path is shorter and the
      inflow and outflow valves are larger than in any other bridge-to-transplant
      device, resulting in greater blood flow at smaller pre-load. Such a device should
      be optimal for bridging transplant candidates who have biventricular failure and
      for whom all other therapies have failed. METHODS: From January 1, 1993, to April
      1, 2002, we prospectively studied 62 consecutive CardioWest TAH implant
      recipients to document safety and efficacy in bridge to transplantation. We used
      multisystem monitoring and multidrug therapy for anti-coagulation in 58 patients
      starting September 1, 1994. RESULTS: Before implantation, patients were
      critically ill with biventricular heart failure. Mortality in this group from the
      time of implantation until transplantation was 23%. Causes of death during device
      support included multi-organ failure (6), sepsis (3), and valve entrapment (2).
      Forty-eight patients underwent transplantation (77%). Forty-two survived to
      hospital discharge (68% of the total, 88% of those undergoing transplantation).
      Adverse events included bleeding (20%), device malfunction (5%), fit
      complications (3%), mediastinal infections (5%), visceral embolus (1.6%), and
      stroke during support (1.6%). The linearized stroke rate was 0.068 events per
      patient-year. CONCLUSIONS: Sixty-eight percent of critically ill transplant
      candidates for whom medical therapy failed were bridged to transplantation with
      the CardioWest TAH and survived long-term. Most deaths that occurred during
      device support were related to pre-implant problems. Infection and stroke were
      rare events. Therefore, we recommend the CardioWest TAH as the biventricular
      bridge-to-transplant device of choice.

PMID- 15261177
TI  - Carvedilol in children with cardiomyopathy: 3-year experience at a single
      institution.
AB  - BACKGROUND: Carvedilol reduces mortality and hospitalization in adults with
      congestive heart failure. Limited information is available about its use in
      children. METHODS: We reviewed the medical records of 24 children with dilated
      cardiomyopathy and left ventricular ejection fraction of <or=40%, who were
      treated with carvedilol as adjunct therapy to angiotensin-converting enzyme
      inhibitors, digoxin and diuretics. RESULTS: Carvedilol was initiated 14.3 +/-
      23.3 (mean +/- SD) months after the diagnosis of cardiomyopathy. Mean age at
      initiation of therapy was 7.2 +/- 6.4 years. The mean initial and maximum doses
      were 0.15 +/- 0.09 and 0.98 +/- 0.26 mg/kg/day. Adverse effects occurred in 5
      patients (21%). Two patients (8%) required discontinuation of the drug within 5
      weeks of the initial dose. The remaining 22 patients tolerated carvedilol for a
      mean follow-up period of 26.6 +/- 14.7 months. Among these 22 patients, mean left
      ventricular ejection fraction improved from 24.6 +/- 7.6% to 42.2 +/- 14.2% (p <
      0.001), and mean sphericity index from 0.86 +/- 0.11 to 0.74 +/- 0.10 (p <
      0.001). New York Heart Association functional class improved in 15 patients
      (68%). One patient (4%) died and 3 (14%) were transplanted. CONCLUSIONS:
      Carvedilol, in addition to standard therapy for dilated cardiomyopathy in
      children improves cardiac function and symptoms; it is well tolerated, with
      minimal adverse effects, but close monitoring is necessary as it might worsen
      congestive heart failure and precipitate asthma. Control studies are necessary to
      assess the effect of carvedilol on mortality and hospitalization rates.

PMID- 15261178
TI  - Interleukin-6 and B-type natriuretic peptide are independent predictors for
      worsening of heart failure in patients with progressive congestive heart failure.
AB  - BACKGROUND: Neurohormones and cytokines have been associated with poor prognosis
      in patients with congestive heart failure. However, direct comparisons between
      them are rare and the best predictor for worsening of heart failure remains to be
      elucidated. The aim of the study was to identify independent predictors for
      worsening of heart failure. METHODS: We studied 100 patients with congestive
      heart failure (LVEF <or=25%). Serum levels of interleukin-6 (IL-6), tumor
      necrosis factor (TNF)-alpha, aminoterminal atrial natriuretic peptide (N-ANP), B
      type natriuretic peptide (BNP), aminoterminal B-type natriuretic peptide (N-BNP),
      norepinephrine (NE) and big endothelin (big ET) were measured at entry into the
      study. Univariate and stepwise multivariate regression analyses were performed to
      compare variables and clinical parameters. The end-point was defined as worsening
      of heart failure. RESULTS: During follow-up (mean 378 days), 30 patients reached
      the defined end-point. Univariate risk factors of worsening of heart failure were
      IL-6 (p = 0.0001), log BNP (p = 0.0001), log N-ANP (p = 0.0259), big ET (p =
      0.0032), log N-BNP (p = 0.0495), NE (p = 0.0013) and LVEF (p = 0.0498).
      Multivariate regression analysis identified IL-6 as the strongest independent
      predictive value for worsening of heart failure (p = 0.0001), followed by log BNP
      (p = 0.0002). Mean IL-6 levels were 1.76 +/- 1.73 in stable patients and 4.62 +/-
      7.98 pg/ml in patients who developed worsening of heart failure. Using a cut-off
      value of 1.66 pg/ml for IL-6 Kaplan-Meier freedom from worsening, heart failure
      was significantly higher in patients below this cut-off point compared with those
      above (p = 0.0002). CONCLUSIONS: IL-6 and BNP independently predict worsening of
      heart failure. A single measurement could help to identify patients at high risk
      for worsening of heart failure and these individuals should be monitored more
      closely.

PMID- 15261179
TI  - Severe diverticulitis after heart, lung, and heart-lung transplantation.
AB  - BACKGROUND: In this study, we reviewed our experience with severe diverticulitis
      in patients who have undergone heart and/or lung transplantation to assess
      whether transplant recipients are at increased risk of having severe
      diverticulitis compared with the general population. METHODS: We reviewed the
      records of patients who underwent heart and/or lung transplantation from 1984 to
      2000, inclusive, and identified patients with severe diverticulitis that required
      surgery or that resulted in death. We compared this incidence with the incidence
      of such complications in the general population, served by the same institution
      during a 2-year period, 1999 to 2000. RESULTS: A total of 953 patients underwent
      transplantation in the study period. The mean follow-up was 57 months, a total
      follow-up of 4528 patient-years. Nine patients (mean age, 54 years) had severe
      diverticulitis that required surgical intervention (8 patients) or that resulted
      in death (1 patient died without surgical intervention). During 1999 to 2000, 16
      patients (mean age, 66 years) from the general population were treated for severe
      diverticulitis that required surgical intervention, 3 of whom died. From census
      and area health data, we found that the study institution serves approximately
      90000 people older than 40 years, with a total follow-up of 180000 patient-years.
      The incidence rate ratio for severe diverticulitis when comparing the transplant
      with the non-transplant groups was 22.2 (95% confidence interval; 9.9-50.0; p <
      0.001). CONCLUSIONS: Patients with severe diverticulitis who have undergone heart
      and/or lung transplantation can be treated surgically with a small mortality
      rate. Transplant recipients probably are at substantially increased risk of
      experiencing severe diverticulitis.

PMID- 15261180
TI  - Predictive value of brain natriuretic peptide in the diagnosis of heart
      transplant rejection.
AB  - AIM: To evaluate the pattern of brain natriuretic peptide (BNP) concentration in
      heart transplant (HT) recipients and its relation to the degree of graft
      rejection determined by endomyocardial biopsy specimen. METHODS: We studied 71
      consecutive HT recipients (62 men, 53 +/- 11 years). The patients underwent 383
      biopsies. Creatinine and BNP concentrations and hemodynamic parameters were
      determined along with the degree of graft rejection using endomyocardial biopsy
      specimens. We considered treatable rejection as International Society for Heart
      and Lung Transplantation Grade >or=2 in the first 90 days and >or=3A thereafter.
      We included a control group of 36 healthy individuals. RESULTS: Brain natriuretic
      peptide concentration was significantly greater among HT recipients (264 +/- 318
      pg/ml) than in controls (17 +/- 16 pg/ml). In the first 90 days, BNP
      concentration was significantly greater among the patients with graft rejection
      (510 +/- 470, n = 84, vs 278 +/- 255, n = 87; p < 0.0001), although the
      corresponding discriminatory capacity was small. After the first 90 days, BNP
      values were similar in patients with and without graft rejection (170 +/- 297, n
      = 17, vs 142 +/- 203, n = 195; p = not significant). Creatinine concentration
      increased with time after transplantation and did not correlate with BNP
      concentration. We observed significant positive correlation between BNP
      concentration and hemodynamic parameters. CONCLUSIONS: Brain natriuretic peptide
      concentration remains increased after HT, with stabilization after the 4th month.
      Brain natriuretic peptide concentrations are slightly greater among patients with
      treatable rejection, particularly in the first 90 days, although BNP
      concentration lacks discriminatory capacity to serve as a guide to performing
      biopsy.

PMID- 15261181
TI  - A longitudinal perspective on neurodevelopmental outcome after infant cardiac
      transplantation.
AB  - BACKGROUND: With improvement in medical outcomes, the current research has
      shifted toward understanding and enhancing the quality of life after pediatric
      heart transplantation. Previous research has indicated that infant heart
      transplant recipients are generally at risk for neurodevelopmental delays;
      however, no longitudinal studies exploring the patterns of development within
      this medical population have been performed. METHODS: Using the Bayley Scales of
      Infant Development-II, 39 children (2 to 38 months of age) who underwent heart
      transplantation in infancy (<1 year) at Loma Linda University Children's Hospital
      were assessed consecutively over time. RESULTS: Mean Mental Development Index
      (MDI) scores for all age groups were within normal limits, except for the age
      ranges of 18 to 23 and 24 to 35 months, which were mildly delayed. Average
      Psychomoter Development Index (PDI) scores for all age groups reflected mildly
      delayed performance, except for the 36- to 38-month age group, which was within
      normal limits. Repeated measures analyses of variance on a sub-set of
      participants with at least 4 consecutive assessments revealed within-subject
      effects on MDI scores (F = 5.7, p < 0.01), but not on PDI scores (F = 1.6, p =
      0.22). Significant decreases in MDI scores at 18 and 28 to 36 months were noted.
      CONCLUSIONS: Motor development in this population was consistently mildly
      delayed. Age-dependent variability in cognitive skills was apparent. The delays
      appeared due to speech/language acquisition (18 months), and abstract
      reasoning/goal-directed behaviors (28 to 36 months). Possible etiologies for
      cognitive delays include test artifacts, auditory functioning and effects of
      immunosuppressive agents. Understanding risk factors in this patient population
      will allow for early and effective intervention.

PMID- 15261182
TI  - Diastolic performance assessed by tissue Doppler after pediatric heart
      transplantation.
AB  - BACKGROUND: Diastolic performance, indexed by tissue Doppler imaging (TDI), has
      been reported to predict cellular rejection in adult heart recipients, but the
      predictive value of TDI after pediatric heart transplantation is unknown.
      METHODS: TDI-derived diastolic performance was studied in 37 pediatric (median
      age 2.54 years) heart recipients in the absence and presence of rejection.
      Maximum velocities in diastole of the left ventricular posterior wall thinning
      (diastvelLVPWmax) and medial mitral valve annulus (MVA) were determined in 160
      echocardiograms from recipients who experienced either no rejection (Group 1, n =
      22) or >or=1 rejection episode(s) (Group 2, n = 14) during the study interval (2
      years). There was 1 death in the immediate post-transplant period not included in
      the analyses. RESULTS: The diastvelLVPWmax determined by TDI in Group 1 increased
      during the first 90 days post-transplant (r = 0.31; p = 0.05), was heart-rate
      dependent (r = 0.591; p < 0.001), and was significantly lower than the veILVPWmax
      determined from digitized M-mode tracings (116 +/- 31 vs 135 +/- 44 mm/s; p <
      0.05). In a sub-group of children transplanted during the study and followed for
      >or=1 year (n = 9), diastvelLPWmax, determined by TDI, was lower in infant
      recipients (n = 6; 106.5 +/- 22 mm/s) than in older recipients (n = 3; 135 +/- 36
      mm/s; p = 0.015). With rejection, diastvelLVPWmax, determined by M mode (147 +/-
      13 vs 104 +/- 11 mm/s; p < 0.05), was decreased compared with baseline recipient
      studies prior to rejection. In contrast, rejection did not significantly change
      diastvelLVPWmax, as determined by TDI. MVA E/A (peak early-to-late diastolic
      velocity ratio) was significantly decreased with rejection (1.37 +/- 0.23 vs 0.92
      +/- 0.22; p < 0.05). As a single parameter, an MVA E/A <1.1 was predictive of
      rejection in 4 of 10 recipients with MVA E/A >or=1.1 pre-rejection. CONCLUSIONS:
      TDI-derived diastvelLVPWmax varied with age at transplant, heart rate and time
      post-transplant. A decrease in TDI-derived MVA E/A, but not diastvelLVPWmax, can
      be of additional predictive value in non-invasive surveillance for rejection in
      pediatric heart recipients.

PMID- 15261183
TI  - A novel sub-population of bone marrow-derived myocardial stem cells: potential
      autologous cell therapy in myocardial infarction.
AB  - BACKGROUND: Several studies have identified beta2-microglobulin-negative (beta2M(
      )) cells as a potential stem cell fraction in the bone marrow of rats and humans.
      We studied the ability of bone marrow-derived beta2M(-) cells to differentiate
      into cardiomyocytes and reconstitute the myocardium in a model of myocardial
      infarction. METHODS: beta2M(-) cells were purified from bone marrow of Lewis rats
      using a magnetic activated cell-sorting technique. beta2M(-) cells, 2.5 x 10(6)
      cells in 100 microl of phosphate-buffered saline (PBS), were transplanted 7 days
      after infarction into a transmural myocardial scar induced by cryoinjury in Lewis
      rats (n = 9). Control Group 1(n = 10) received a 100-microl injection of PBS, and
      Control Group 2 (n = 15) received no injection. The beta2M(-) cells were labeled
      before transplantation, using the membrane fluorescent intercalated dye, PKH26.
      Repopulation was examined at 6 and 8 weeks after transplantation. Differentiation
      of beta2M(-) cells into cardiac myocytes was determined by the colocalization of
      troponin and PKH26 to the same cell, utilizing immunohistochemistry, ultraviolet
      photomicroscopy and fluorescence microscopy on 6-microm serial sections. Area of
      engraftment within the scar was calculated by planimetry. RESULTS: The treatment
      group had multiple islands of de novo-formed myocardium within the fibrous matrix
      of the transmural scar (mean area 35 +/- 4.2% of scar area at 6 and 8 weeks).
      These cells colocalized cardiac-specific troponin and PKH26. Using these
      techniques, no myocardial islands were seen in the control groups. Before
      transplantation, beta2M(-) cells were troponin-negative. CONCLUSIONS: This study
      demonstrates that beta2M(-) cells represent a novel sub-population of bone marrow
      derived stem cells capable of successful and substantial engraftment in areas of
      transmural myocardial scar, with de novo formation of cardiac myocytes. The
      functional significance of this observation is being studied.

PMID- 15261184
TI  - Acute effects of direct cell implantation into the heart: a pressure-volume study
      to analyze cardiac function.
AB  - BACKGROUND: To safely implant cells into the myocardium, we must establish a
      volume that prevents compromising cardiac performance. We studied pressure-volume
      (PV) to investigate the adverse effects of direct cell implantation in the acute
      phase. METHODS: We used 21 minipigs. In the normal heart model, we studied PV by
      measuring various parameters (including end-systolic pressure, end-systolic
      elastance, dp/dtmax, end-diastolic volume, and time constant of isovolumetric
      left ventricular pressure fall [Tau]). We injected solutions into the left
      ventricular free wall (15 cm(2)). Sampling points were at baseline and after
      injection of saline (Group I, n = 4) or of blood (Group II, n = 4) at volumes of
      1 ml and 10 ml up to 30 minutes after injection. In Group II, we injected
      additional blood (10 ml) 4 times. In the ischemic heart model, 1 month after
      ligating the left anterior descending artery, we injected 1 ml saline (Group III,
      n = 4), bone marrow mononuclear cells (10(8) cells/1 ml; Group IV, n = 4), or
      bone marrow stromal cells (10(8) cells/1 ml; Group V, n = 3). We studied PV
      before and after injection. RESULTS: In Group I, we found no significant changes
      in parameters. In Group II, end-diastolic volume after 10-ml injection (24.4 +/-
      3.6 ml) was smaller than end-diastolic volume at baseline (29.5 +/- 5.8 ml, p <
      0.01). Tau after 10-ml injection (39.4 +/- 5.3 msec) was greater than at baseline
      (35.6 +/- 4.0 msec, p < 0.01). One pig died of ventricular fibrillation after a
      20-ml injection of blood. We observed no detrimental effects in Groups III, IV,
      and V. CONCLUSIONS: More than 10 ml cell suspension compromised diastolic
      function. We safely performed direct injection of bone marrow cells (1 x 10(8)/1
      ml).

PMID- 15261185
TI  - Comparison of surgical procedures for vascular and airway anastomoses that
      utilize a modified non-suture external cuff technique for experimental lung
      transplantation in rats.
AB  - BACKGROUND: Lung transplantation in rats is technically difficult and results may
      vary. The non-suture cuff technique (non-suture [NS]), which involves using a
      cuff for anastomoses of vessels and airways, is commonly utilized to perform
      transplant procedures. However, the standard bronchial cuff may occlude the
      lumen, resulting in diminished graft survival. In contrast, the non-suture cuff
      technique for vascular anastomoses with bronchial suturing (bronchial suture
      [BS]), although more technically difficult, is known to have prolonged bronchial
      patency. We developed a "modified" NS technique that uses a larger and longer
      cuff for anastomoses and compared the efficacy of this procedure to the BS
      technique for lung transplantation. METHODS: The BS procedure was performed in
      146 transplant procedures. The modified NS procedure, which uses a larger cuff
      than the standard NS procedure, was performed in 113 procedures. RESULTS:
      Although total ischemic times were comparable, the total operation time in the NS
      group was significantly shorter than in the BS group (p < 0.0001). Bronchial
      leakage occurred in 9.6% of BS group patients and 0% of NS group patients.
      Survival rates were comparable between groups. Although the BS technique is
      widely acknowledged to provide prolonged patency of bronchial anastomosis, graft
      survival in the NS group was observed up 17 months post-transplant. CONCLUSIONS:
      These data show that the NS technique, which is less technically difficult,
      results in shorter operative times compared with the BS procedure, and results in
      durable anastomoses of lung grafts.

PMID- 15261186
TI  - Sexual health issues after lung transplantation: importance of cervical
      screening.
AB  - To determine the incidence and outcomes of human papillomavirus infection and
      cervical abnormalities after lung transplantation, we performed a retrospective
      cross-sectional study of all 166 female recipients who underwent transplantation
      between February 1989 and June 2001 at our institution. The incidence of low
      grade epithelial abnormality of the cervix, cervical intra-epithelial neoplasia
      (CIN) 1, and the earliest pre-cancerous changes of the cervical epithelial cells,
      CIN 3, in the post-transplant cohort was 42.2 and 30, respectively, per 1000
      women screened compared with 8.3 and 6.2 per 1000 women screened (20-69 years
      old) in a large reference population. We conclude that the incidence of cervical
      abnormalities in lung transplant recipients is significantly greater than in the
      general population. The importance of regular surveillance in immunosuppressed
      patients to decrease the burden of disease from this potentially fatal but
      treatable condition is emphasized.

PMID- 15261187
TI  - Pregnancy in heart transplant recipients.
AB  - The aim of this report is to present data from Italian cardiac transplant centers
      assessing pregnancy after cardiac transplantation. Our retrospective survey
      included 10 pregnancies occurring in 7 patients during January 1991 to February
      2002. Eight pregnancies were completed successfully and 2 abortions were reported
      (frequency rate 20%). No complications were observed during pregnancy or after
      delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term.
      One baby presented congenital talipes valgus. Pediatric development was
      uneventful. The data from the literature and our series show that a
      multidisciplinary approach is mandatory. The course of pregnancy is usually
      normal and the maternal and fetal outcomes are usually favorable. Although no
      fetal malformations have been reported, prolonged follow-up of these infants is
      required.

PMID- 15261188
TI  - Orthotopic heart transplantation in a child with histiocytoid cardiomyopathy.
AB  - We report a case of histiocytoid cardiomyopathy in a 30-month-old child. This
      rare disorder has been identified in <100 patients worldwide and no previous
      reports of cardiac transplantation with this condition have been identified. We
      reviewed the clinical and pathologic findings and compared them to previous
      studies.

PMID- 15261189
TI  - Strongyloides hyperinfection syndrome after heart transplantation: case report
      and review of the literature.
AB  - Stronglyoides hyperinfection syndrome (SHS) is an augmentation of the infective
      life cycle of S stercoralis. Immunosuppressed patients, especially those taking
      corticosteroid therapy, are at risk. We present a case of fatal SHS with
      disseminated infection following orthotopic heart transplantation. The patient
      was treated with increased doses of immunosuppressive medications for graft
      rejection, including corticosteroids. A review of the literature describing the
      pathophysiology, host defenses and treatment of SHS is also presented. Diagnostic
      tests for S stercoralis are reviewed. SHS should be part of the differential
      diagnosis in immunosuppressed patients presenting with sepsis or gastrointestinal
      or pulmonary complaints. Pretransplant evaluation for parasitic infections,
      including strongyloidiasis, should occur in endemic areas or in patients at risk
      for occult infestation.

PMID- 15261190
TI  - Bilateral lung transplantation for metastatic leiomyosarcoma.
AB  - As increased experience is gained in the field of lung transplantation, novel
      applications for this life saving therapy will evolve. We have described a case
      of bilateral lung transplantation in a young patient with respiratory failure
      secondary to metastatic leiomyosarcoma that was limited to the lungs. While lung
      transplantation for malignancy remains a controversial area, this case
      illustrates that lung transplantation can provide improved quality and quantity
      of life for highly selected patients with malignant disease.

PMID- 15261191
TI  - Use of catecholamines in cardiac donors: what is the real limit?

PMID- 15261192
TI  - Rapamycin and chronic lung rejection.

PMID- 15261193
TI  - Effects of timing of l-arginine supplementation after deep hypothermic storage
      and reperfusion.

PMID- 15261194
TI  - High-resolution chromoendoscopy in the esophagus.
AB  - The major role for chromoendoscopy in the esophagus is the identification of
      premalignant or early cancerous lesions. In combination with high-resolution or
      magnification endoscopes, chromoendoscopy can potentially increase the diagnostic
      yield of clinically relevant lesions. Preliminary data have indicated a good
      correlation of findings using this technique to histopathologic readings. The
      ultimate goal of chromoendoscopy in combination with high
      resolution/magnification endoscopy is the determination of histology without
      obtaining tissue samples. In this article we review the different stains, the
      technical aspects, and current data in esophageal chromoendoscopy. We summarize
      possible clinical applications of these techniques and future directions of their
      use in esophageal diseases.

PMID- 15261195
TI  - Chromoendoscopy of the colon.
AB  - Chromoendoscopy is a technique that uses tissue stains to better characterize,
      delineate, or highlight the gastrointestinal mucosa. Chromoendoscopy of the colon
      has the potential to significantly aid the endoscopist in the recognition and
      identification of mucosal abnormalities ranging from inflammation to neoplasia.

PMID- 15261196
TI  - Enhanced magnification endoscopy in the upper gastrointestinal tract.
AB  - In diseases such as Barrett's esophagus and celiac disease, the mucosal
      abnormality is patchy or irregular, highlighting the need for targeted biopsies.
      Enhanced magnification endoscopy is an effective, readily available method that
      can be used to assist in target biopsies and endoscopic diagnosis leading to an
      endoscopic classification system. The technique is not difficult and adds only an
      additional 5 to 10 minutes to a standard endoscopic procedure;however, most
      endoscopists never receive instruction in magnification endoscopy during their
      training. The value of this technique is still being explored, but the
      improvement in diagnostic accuracy will have an impact on decreasing morbidity
      and mortality without a large increase in cost. Increased use of this technique
      will aid in the diagnosis of celiac disease and simplify the classification
      system for Barrett's esophagus. Using enhanced magnification endoscopy at
      multiple centers in studies will help to determine the intra- and inter-observer
      variability, define the endoscopic criteria for dysplasia and early neoplastic
      changes, and standardize the visualized mucosal patterns more clearly.

PMID- 15261197
TI  - Photodynamic diagnosis in the gastrointestinal tract.
AB  - Clinical data on photodynamic diagnosis for the detection of premalignant and
      malignant lesions in the gastrointestinal tract are encouraging so far. A major
      benefit of using autofluorescence is the lack of side effects because no
      sensitizer has to be applied.However, highly sophisticated detection systems are
      needed to enhance the weak autofluorescence-based fluorescent signal. New
      prototypes of autofluorescence video endoscopes are under way and will be
      decisive for further clinical use, especially because results of recently
      published studies have been disappointing.

PMID- 15261198
TI  - Endoscopic fluorescence spectroscopic imaging in the gastrointestinal tract.
AB  - Fluorescence detection is one of a series of new optical biopsy techniques that
      have been adapted and evaluated for implementation in gastrointestinal endoscopy.
      Endogenous fluorescence enables the detection of metabolic and structural changes
      in human tissue and thus may offer information for the detection of early stage
      dysplastic and malignant lesions of the mucosa that remain invisible in white
      light endoscopy. Tissue fluorescence can be detected by point-spectroscopic
      sampling of the mucosa or by processing the fluorescence information to generate
      an endoscopic image. Different approaches have been evaluated in pilot studies,
      and the results in terms of high diagnostic sensitivity and specificity are
      encouraging. However, large multi-center trials are necessary to evaluate the
      accuracy and predictability of these new optical tools for the endoscopic
      diagnosis of early cancerous lesions in the gastrointestinal tract.

PMID- 15261199
TI  - Elastic scattering spectroscopy for detection of dysplasia in Barrett's
      esophagus.
AB  - Elastic scattering is a cheap and simple-to-use tool that holds the promise of
      rapid and accurate diagnosis in many applications,including dysplasia arising in
      Barrett's esophagus. It is being developed as an optical biopsy technique, but
      preliminary work shows that it may be possible to use this approach as a field
      detection device. Even as a point measurement technique or optical biopsy, the
      technique may become an invaluable tool to endoscopists. This article focuses on
      elastic scattering spectroscopy (also known as diffuse reflectance spectroscopy).

PMID- 15261200
TI  - The combined use of fluorescence, reflectance, and light-scattering spectroscopy
      for evaluating dysplasia in Barrett's esophagus.
AB  - Intrinsic fluorescence, diffuse reflectance, and light-scattering spectroscopy
      provide complementary information on biochemical and morphologic information
      extending potentially from the molecular to the tissue level. Model-based
      spectral analysis in each case yields results about specific tissue parameters in
      a quantitative manner.Preliminary studies demonstrate that these parameters can
      be used for the development of algorithms that can detect dysplastic changes in
      patients with Barrett's esophagus (BE) with high sensitivity and specificity.
      Studies validating tri-modal spectroscopy based algorithms and real-time
      spectroscopic data analysis are under way to provide a more accurate and
      extensive assessment of the potential of this approach as a clinical noninvasive
      tool that could improve the management and treatment of BE dysplasia.

PMID- 15261201
TI  - Reflectance spectrophotometry for the assessment of mucosal perfusion in the
      gastrointestinal tract.
AB  - Reflectance spectrophotometry (RS) is an optical technology that has been used
      for nearly three decades in the measurement of tissue hemoglobin oxygen
      saturation in the gastrointestinal tract. The technology has evolved
      substantially throughout this period,and commercial devices are now available for
      use in clinical trials. Numerous studies have used RS to investigate the
      importance of mucosal perfusion in disorders such as ulcer disease, portal
      hypertension, and septic shock. More recently, the technique has been applied to
      measure changes in perfusion in response to infusion of vasoactive medications
      and maneuvers such as cardiopulmonary bypass. The results of current trials
      investigating the application of RS in critical care monitoring and vascular
      interventions will likely determine whether the technique will evolve from
      predominantly a research tool to a clinically useful device.

PMID- 15261202
TI  - Optical coherence tomography in the gastrointestinal tract.
AB  - Conventional gastrointestinal endoscopic instruments have provided ready access
      to the mucosal surface of the esophagus, stomach,small intestinal, colon, bile
      duct, and pancreatic duct. The evolution of endoscopic ultrasonography has
      provided an additional dimension to the clinical application of modern endoscopy
      and imaging technology.

PMID- 15261203
TI  - Diagnosis of Barrett's esophagus using optical coherence tomography.
AB  - The presence of Barrett's esophagus (BE) is determined by histopathologic
      analysis of biopsy specimens obtained during upper endoscopy. The accuracy of
      endoscopy for the diagnosis of BE is surprisingly poor, however. Optical
      coherence tomography (OCT) is an optical technology that has shown promise as a
      powerful new tool to study BE. Of all the methods of optical biopsy discussed in
      this issue,perhaps OCT comes closest to this goal in that it provides a two
      dimensional image that correlates with traditional histopathologic excisional
      biopsy.

PMID- 15261204
TI  - In vivo observation of living cancer cells in the esophagus, stomach, and colon
      using catheter-type contact endoscope, "Endo-Cytoscopy system".
AB  - A catheter-type endomicroscope has been developed with a maximum magnifying power
      of 1100 times. Living cancer cells in the esophagus, stomach, and colon were
      successfully observed in high-resolution images. The "Endo-Cytoscopy system"
      (prototype,Olympus Optical, Co., Tokyo, Japan) is a catheter-based probe capable
      of passage through the accessory channel of the endoscope(GIF-1T, Olympus).
      Methylene blue solution was used for vital staining of the in vivo
      gastrointestinal mucosa. Living cells in both normal mucosa and malignant tissue
      were clearly demonstrated in luminal organs. In particular, the nucleus, cell
      body, and nucleolus were clearly demonstrated with high-quality images similar to
      those of conventional cytology. This novel technology has the potential to
      provide an in vivo histologic diagnosis via "optical biopsy" and virtual
      histology.

PMID- 15261205
TI  - In vivo pathology: microendoscopy as a new endoscopic imaging modality.
AB  - Confocal microendoscopy permits direct observation of pathologic change at the
      microscopic level rather than traditional inference based on indirect changes at
      the macroscopic (cell) level. The main benefit includes earlier detection of
      precancerous and cancer conditions through improved biopsy selection and
      examination and more cost-effective solutions to screening and surveillance.
      Numerous outstanding research and commercial groups with varying approaches to
      confocal microendoscopy are allocating significant efforts to making the
      technology commercially available. The initial instruments will likely be geared
      toward screening for and surveillance of esophageal and colon-related conditions.
      Future developments related to greater functionality, improved ease of use, and
      automated analysis are likely to facilitate adoption and use of the technology.
      Clinical gastroenterologists should look forward to the potential of confocal
      microendoscopy as a logical and needed modality to advance the field of
      gastroenterology.

PMID- 15261208
TI  - Reference axes for reconstruction of the knee.
AB  - Knee alignment is an essential problem in reconstructive surgeries of the knee.
      Quite a number of reference parameters have been suggested to help the surgeons
      to get proper alignment during operations. In this article, most commonly used
      reference axes, both for the axial and the rotational, are reviewed, in an
      attempt to highlight their reliabilities and clinical relevance.

PMID- 15261209
TI  - Long-term local effects of carbon fibre in the knee.
AB  - A radiological and histological analysis of five knee joints after a minimum of
      15 years following the implanting of carbon fibre, which had been used as a
      treatment for knee instability, was undertaken. All patients underwent total knee
      replacement for secondary osteoarthritis. Histological analysis demonstrated a
      variable amount of macroscopically visible carbon particles in the synovium,
      hyaline cartilage and menisci. At microscopy these particles were found in
      association with fibrous tissue adjacent to bone with no acute inflammatory
      changes. No intact carbon fibre ligament was noted within the joint, small
      portions of the old ligament were covered with a thin fibrous layer but there was
      no evidence of any structure resembling neo-ligament. Extra articularly the
      carbon fibre was covered with a thick fibrous sheath with no active inflammation
      changes inflammation. In the bone tunnels, the carbon fibre-bone interface showed
      an apposition of the bone to the carbon fibre without any interposing fibrous
      sheath. Carbon fibre bonds directly with the bone without fibrous interposition.

PMID- 15261210
TI  - The accuracy of magnetic resonance imaging in diagnosing chronic posterior
      cruciate ligament injury.
AB  - Magnetic resonance imaging (MRI) is widely believed to be highly accurate in
      diagnosing injuries of the posterior cruciate ligament (PCL). The aim of this
      study was to determine the accuracy of MRI in diagnosing chronic PCL injury. MRI
      was performed on 10 knees with a clinical and arthroscopic diagnosis of a PCL
      injury sustained at least 6 months previously. Seven experienced musculoskeletal
      radiologists subsequently reviewed the scans. Their accuracy in diagnosing a PCL
      injury was 57% (40-80%). Thus, although MRI may be reliable in diagnosing acute
      PCL injury, MRI is not so reliable in evaluating chronic injuries. We postulate
      that, in the case of a chronic PCL injury, healing in continuity may occur,
      producing an intact but lax ligament. As demonstrated by our study, MRI may then
      be less accurate. This should be borne in mind when assessing the MRI scans of a
      suspected chronic PCL injury.

PMID- 15261211
TI  - Regional differences in the healing potential of the meniscus-an organ culture
      model to eliminate the influence of microvasculature and the synovium.
AB  - Meniscal healing is well known to be region-specific, and this is thought to be
      mainly due to its specific vascularity. The purpose of this study was to assess
      regional differences in the intrinsic healing potential of the meniscus, using an
      organ culture model to eliminate the influence of microvasculature and the
      synovium. A full-thickness circular defect, 1.5 mm in diameter, was created in
      the inner avascular zone in meniscal explants from rabbits. As a control, a
      column of 1.5 mm in diameter was removed then replanted in the area where it had
      been obtained (Group C). In the experimental group, a 1.5 mm-diameter meniscal
      graft obtained from the peripheral zone of the same specimen was implanted in the
      damaged area (Group T). These meniscal explants were cultured for 2, 4 or 6
      weeks, and the relationship between the recipient tissue and the graft was
      examined using both gross and histological semiquantitative scoring. The 6-week
      gross-examination showed that the openings were more apparent in Group C, and the
      score of Group T was significantly higher than that of Group C (P=0.0152).
      Histologically, the healing responses after both 4 and 6 weeks of incubation were
      significantly better in Group T than in Group C (P=0.0237, 0.0281). These results
      using organ culture demonstrate that intrinsic healing potential differs even
      without the influence of vascular supply and the synovium, indicating that the
      superior healing potential in the peripheral zone may contribute to the good
      meniscal healing in this location.

PMID- 15261212
TI  - Knee scores in a 'normal' elderly population.
AB  - Many scoring instruments are now available for assessment of outcome after knee
      replacement. We performed a community study to record the three most frequently
      used knee scores in the UK in a 'normal' elderly population with no history of
      knee, hip, spine or lower limb disorder. The Oxford Knee Score (OKS), Bristol
      Knee Score (BKS), and American Knee Society Score (AKSS) were recorded in 100
      volunteers whose mean age was 72 years. Normalised median scores in this
      population were 97% (42-100), 96% (69-100) and 98% (46-100), respectively.
      Significant negative correlations were found to exist between knee score and
      increasing age (P<0.001) and presence of coexistent 'major' medical conditions
      (P<0.001). The 'function' component of each score was the aspect of the score
      most influenced by these demographic variables. Comparison of outcomes after knee
      replacement on the basis of knee scores should take account of demographic
      variables.

PMID- 15261213
TI  - A parallel approach: the impact of schuss radiography of the degenerate knee on
      clinical management.
AB  - Schuss radiographs are PA weight bearing views of the knee taken in 30 degrees of
      flexion. Several studies have shown them to be more sensitive detectors of
      osteoarthritic changes in the knee than standard extension AP views. We compared
      the plans of management proposed by eight consultant orthopaedic surgeons to two
      case presentations of each of a series of 50 patients with tibiofemoral
      osteoarthritis. The clinical and radiological information provided on each
      patient was identical in the two presentations except that on one occasion the
      surgeons were shown the extension AP radiograph while on the other it was
      replaced by the schuss view. The panel altered their management plan in over 40%
      of cases. This represented a reduction of almost 50% in arthroscopies in the
      schuss group with a move towards definitive surgery. The total number of
      procedures proposed was also reduced. The radiograph was useful determining the
      management of patients with predominantly lateral, as well as medial or
      generalised symptoms. We conclude that the schuss radiograph is a valuable tool
      in the assessment of knee osteoarthritis the use of which can alter clinical
      management. By reducing non-therapeutic arthroscopies it may significantly reduce
      total number of operations to be performed in this patient group.

PMID- 15261214
TI  - Reducing lateral skin flap numbness after total knee arthroplasty.
AB  - One hundred and thirteen knees were assessed for lateral skin flap numbness, 5
      227 weeks following IB2 total knee arthroplasty. The final 53 had the numb area
      measured. To define the anatomy of the cutaneous nerves we dissected four
      cadaveric knees. Eighty-six percent of patients had a numb area on objective
      assessment but only 60% had subjective numbness, 62% of which had improved.
      Patients had a larger numb area if they were aware of a numb patch, had a scar
      over 22 cm long or were less than 25 weeks following surgery. We conclude that
      not all patients will get lateral skin flap numbness and improvement occurs with
      time. The area of numbness can be reduced by using a shorter proximal incision,
      which preserves branches of the medial and intermediate cutaneous nerves of
      thigh.

PMID- 15261215
TI  - Effect of total knee arthroplasty on patients' bone quality-ultrasound
      measurement of the calcaneus.
AB  - We used ultrasonographic heel measurements to compare the bone quality of
      patients who underwent total knee arthroplasty (TKA), age-matched controls and
      patients who suffered from hip fracture. The broadband ultrasound attenuation
      (BUA; dB/MHz) of the TKA (70), control (70) and hip fracture (107) groups was
      42.2+/-15.5, 40.2+/-14.9 and 22.9+/-13.3, respectively. The hip fracture group
      was significantly different from both the TKA and control groups (P<0.0001). The
      TKA group had better BUA than the control group, although the difference was not
      significant (P=0.712). The increase in activity after artificial replacement of
      an arthritic joint might result in bone quality equivalent to that of controls.
      Considering that none of TKA patients suffered from hip fracture in the follow-up
      period, which ranged from 62 to 113 months, TKA might contribute to a decrease in
      the risk of later hip fracture, by allowing increased mobility and maintaining or
      improving bone quality.

PMID- 15261216
TI  - Periprosthetic femoral bone loss after total knee arthroplasty: 1-year follow-up
      study of 69 patients.
AB  - The clinical survival of joint arthroplasties is related to the quality of the
      surrounding bone environment. Bone mineral density (BMD) is an important measure
      of bone strength and quality. The aim of this prospective study was to measure
      the quantitative changes in BMD in the distal femur after cemented total knee
      arthroplasty (TKA) in osteoarthrotic knee joints. Sixty-nine patients with TKA
      were scanned postoperatively using dual-energy X-ray absorptiometry (DXA) within
      a week of surgery, and at 3-, 6-, and 12-month follow-ups. An average decrease in
      bone density of 17.1% (mean range of 12.1-22.8%) was measured adjacent to the
      prosthesis at the 12-month follow-up (repeated measures ANOVA P<0.0005). Bone
      loss was most rapid during the first 3 months after TKA. The clinical status and
      function parameters of the knee joint, evaluated by the American Knee Society
      (AKS) score, had improved significantly on the preoperative values at the three-
      and 12-month follow-ups (P<0.0005). However, improvement in the AKS score was not
      associated with periprosthetic BMD change (P=0.204), whereas age (P=0.067) and
      body mass index (P=0.019) correlated with BMD loss for the total metaphyseal
      region of interest (ROI), by repeated measures ANOVA. We suggest that the
      observed periprosthetic bone loss was mainly the result of prosthesis-related
      stress-shielding.

PMID- 15261217
TI  - Performance characteristics of ultrasound of the knee in a general radiological
      setting.
AB  - Ultrasound of the musculoskeletal system is an attractive imaging modality due to
      the lack of ionising radiation, cost and ease of availability. A role has been
      established in the shoulder and pediatric hip but not in the knee. Ultrasound
      studies of the knee performed at six general radiological practices without
      established musculoskeletal expertise were compared with clinical examination in
      56 patients. Final diagnoses were established by arthroscopy and/or MRI. The
      sensitivity and specificity for detection of superficial lesions in the knee were
      88 and 41% for clinical examination and 32 and 59% for ultrasound. For deep
      lesions sensitivity and specificity were 61 and 64% for clinical examination and
      13 and 100% for ultrasound. Ultrasound studies of the knee in a general
      radiological practice do not offer significant information above clinical
      examination.

PMID- 15261218
TI  - The evaluation of the proximal tibiofibular joint for patients with lateral knee
      pain.
AB  - In contrast to important functions of the proximal tibiofibular joint (PTFJ),
      there appear a few clinical and radiological studies concerning the PTFJ
      pathologies. Although almost all of the joints have been investigated in detail
      by MRI, review of the literature reveals none on the pathologies of PTFJ. Thirty
      eight knees of 32 patients with lateral knee pain were evaluated clinically and
      radiologically. All had tenderness over the PTFJ and lateral hamstring tightness.
      MRI examination revealed effusion of the PTFJ in 22 knees and partial ruptures of
      anterior or posterior tibiofibular ligament, lateral collateral ligament or
      biceps femoris tendon in 25 knees. All patients were treated by manipulative
      physiotherapy of the PTFJ and strengthening and stretching exercises of the
      surrounding structures. All patients were followed-up 12-36 months (mean 28
      months) after the treatment protocol, and complete relief of the symptoms was
      recorded in 28 of the 38 knees. Although spontaneous pain was not present in five
      patients, there was tenderness over the PTFJ by palpation. No change in the
      symptoms was recorded in five patients. These results suggest that PTFJ
      pathologies should be kept in mind in the evaluation of lateral knee pain and MRI
      examination provides useful information.

PMID- 15261219
TI  - The role of timing of tourniquet release and cementing on perioperative blood
      loss in total knee replacement.
AB  - The purpose of our study is to estimate the effect of tourniquet release and
      cementing in perioperative blood loss associated with total knee arthroplasty.
      Eighty patients were randomly allocated into two equal groups concerning the
      timing of tourniquet release. Group A: patients with tourniquet release and
      haemostasis before wound closure and group B: patients with tourniquet release
      after skin closure and compressive bandaging. These groups were further
      subdivided in two subgroups (+ and -) depending on cementing or not of the tibial
      tray only. The total blood loss averaged 961 ml in group A and 692 ml in group B,
      while it was estimated 763 ml in the cemented group and 890 ml in the non
      cemented group. The total blood loss within subgroups was Group A+ 904 ml, Group
      A- 1017 ml, Group B+ 622 ml and Group B- 762 ml. The mean number of blood units
      transfused per patient was 4.7 in Group A and 4.0 in Group B, while the mean
      operating time was 79 min and 66 min, respectively. Complications such as deep
      vein thrombosis, haematomata and minor wound complications occurred in patients
      of Group A and Group B, 0 and 2, 0 and 2, 8 and 11, respectively. Intraoperative
      tourniquet release seems to be related with significantly greater blood loss
      (P<0.001) and demands in blood transfusion P<0.05 as well as a longer operating
      time (P<0.001). Cementing of total knee replacements has a better haemostatic
      role compared to non-cemented prosthesis (P<0.05). Even though complications were
      more in postoperative tourniquet release group, no statistically significant
      difference was found between group A and B. Postoperative tourniquet release
      seems to offer better conditions of haemostasis probably due to the better
      controlled fibrolytic activity.

PMID- 15261220
TI  - Inclination of the joint line in supracondylar osteotomy of the femur for valgus
      deformity.
AB  - The inclination of the joint line after supracondylar osteotomy of the femur for
      valgus deformity was studied in 22 patients and 26 knees. The patients (four
      males and 18 females) were 17-77 years old (mean, 49.5 years). The obliquity of
      the joint line was measured in positive degrees (medial inclination) and negative
      degrees (lateral inclination). Mean obliquity was +3.1 degrees in the pre
      operative study and -2.0 degrees in the post-operative study. A more horizontal
      joint line was obtained following surgical treatment (mean correction: 5.0
      degrees ).

PMID- 15261221
TI  - Intra-articular calcification in primary hyperparathyroidism.
AB  - We report a case of intra-articular calcification involving the knee joint
      secondary to primary hyperparathyroidism. This caused significant disability to
      the patient and following excision of the calcified mass the patients knee
      function returned to normal. This feature of hyperparathyroidism has not been
      previously reported.

PMID- 15261222
TI  - Patello-femoral joint pain due to unusual location of localised pigmented
      villonodular synovitis-a case report.
AB  - Localised pigmented villonodular synovitis (PVNS) is a rare condition usually
      affecting the knee. It can be a difficult condition to manage with an average
      delay in diagnosis of 4.4 years. We describe a case of a localised PVNS lesion
      interposed between the patello-femoral joint, presenting as 'anterior knee pain'.
      To our knowledge this has not previously been reported. The lesion was completely
      excised at arthroscopy resulting in complete resolution of symptoms. Solitary
      lesions of PVNS should also be considered in the differential diagnosis of
      unexplained 'anterior knee pain'.

PMID- 15261223
TI  - Arthroscopic repair of chronic capsular defect after popliteal cystectomy.
AB  - We present an arthroscopic repair technique (all inside suture) for chronic
      capsular defect of posterolateral space of knee joint developed after previous
      popliteal cystectomy. We use a transseptal posteromedial viewing portal, and two
      posterolateral working portals. This procedure can be an alternative to an open
      repair technique for a posterior capsular defect after open cystectomy.

PMID- 15261224
TI  - Dementia with Lewy bodies.

PMID- 15261225
TI  - Murray Alexander Falconer and the Guy's-Maudsley Hospital seizure surgery
      program.
AB  - The 1949 appointment of Murray Falconer to the neurosurgical post of Guy's
      Hospital, London, resulted in the creation of an extremely productive seizure
      surgery program, in the early days of this discipline. In association with the
      Institute of Psychiatry at the Maudsley Hospital, his program produced in-depth
      research on the neuropsychiatry, the neuropathology and the psychosocial follow
      up of temporal lobe epilepsy treated by surgical ablation. These results
      constitute a very significant landmark in the history of the early days of the
      neurosurgical attack on refractory epilepsy.

PMID- 15261226
TI  - Photodynamic therapy of brain tumours: evaluation of porphyrin uptake versus
      clinical outcome.
AB  - The objective of this study was to investigate whether the level of the
      photosensitizer haematoporphyrin derivative (HpD) uptake measured in tissue
      samples taken from brain tumour patients was associated with survival post
      treatment with photodynamic therapy (PDT). The mean HpD uptake in tumour tissue
      was significantly higher in glioblastoma multiforme than anaplastic astrocytoma.
      Recurrent tumours had a higher mean uptake compared to primary tumours, which was
      evident in all grades of tumour. Among patients with GBM, there was a significant
      association between greater HpD uptake and survival (HR = 0.26 [0.12, 0.59], p =
      0.001). There was also some evidence of a weak association between greater HpD
      uptake and survival among patients with AA, although the result was inconclusive
      (HR = 0.73 [0.32, 1.71], p = 0.472).

PMID- 15261227
TI  - Endoscopic transnasal intradural repair of anterior skull base cerebrospinal
      fluid fistulae.
AB  - This study presents the techniques and results of endoscopic diagnosis and repair
      of cerebrospinal fluid (CSF) fistulae involving the anterior skull base and
      paranasal sinuses. DESIGN: A retrospective cohort study of all consecutive
      patients undergoing endoscopic repair of anterior skull base CSF fistulae.
      SETTING: Tertiary referral institutions. MATERIALS AND METHODS: Fifty-two
      patients underwent endoscopic repair of CSF fistula. Thirteen cases were
      traumatic in origin, 11 spontaneous not associated with meningoencephalocele and
      12 with meningoencephalocele. Eleven were iatrogenic and five associated with
      transphenoidal pituitary surgery, two acute and three delayed following
      radiotherapy. The average age of patients was 43 and the male to female ratio was
      2:1. A variety of techniques were used to repair the dural defect. In the
      majority of cases placement of a fat plug on the intracranial surface of the dura
      was performed. RESULTS: Forty-seven of the 52 patients had successful primary
      endoscopic repair of the CSF fistula and skull base defect. Five patients
      required a repeat procedure due to early failure of the repair. After an average
      follow-up of 27 months no patient has had any recurrence of leak giving a primary
      closure success rate of 90% and secondary closure rate of 100%. CONCLUSIONS: The
      endoscopic transnasal approach for repair of anterior skull base CSF fistula is a
      reliable technique and is now the procedure of choice for patients presenting
      with this problem.

PMID- 15261228
TI  - A randomized crossover comparative study of aspirin, cilostazol and clopidogrel
      in normal controls: analysis with quantitative bleeding time and platelet
      aggregation test.
AB  - The effects of three antiplatelet drugs, aspirin, clopidogrel and cilostazol,
      were examined and compared using a quantitative bleeding time (QBT) test
      apparatus. In 12 healthy adult male subjects, a QBT test and platelet aggregation
      test were performed before and after medication. Cilostazol was found to be as
      effective as aspirin and clopidogrel in inhibiting platelet aggregation.
      Following the oral administration of aspirin and clopidogrel for 7 days, the
      bleeding time was significantly prolonged. In contrast, none of these QBT
      parameters were altered by the cilostazol treatment. This suggests that
      cilostazol has potent efficacy in inhibiting platelet aggregation without
      prolonging the bleeding time and changing the bleeding pattern.

PMID- 15261229
TI  - Clinical and genetic analysis of a family with PROMM.
AB  - PROMM (proximal myotonic myopathy) and DM2 (myotonic dystrophy Type 2) are
      autosomal dominant multisystem disorders that have both been linked to chromosome
      3q. Recently, the genetic basis of DM2 has been defined by a '(CCTG)(n)'
      expansion mutation in intron 1 of the ZNF9 gene. We identified and studied a
      multigenerational family in which five members had clinical features consistent
      with PROMM. Two affected members were available for detailed clinical,
      electrophysiological, radiological and genetic analysis. Our study confirms that
      the PROMM phenotype is associated with DM2-(CCTG)(n) expansion mutations. In
      addition, our results may extend the clinical spectrum of manifestations to
      include vestibular symptoms.

PMID- 15261230
TI  - Gender disparities in serum electrolytes levels after subarachnoid hemorrhage.
AB  - We retrospectively studied 133 patients with subarachnoid hemorrhage (SAH) to
      assess whether there was any gender disparity in serum electrolytes levels
      throughout the clinical course. Serum concentrations of sodium and potassium were
      measured in all patients, while catecholamines or antidiuretic hormone were
      assessed in a number of cases. Female SAH-patients had lower potassium level
      (3.29 +/- 0.47 mEq/L) than did male patients (3.68 +/-0.38) on the first day of
      SAH. This gender disparity continued to the beginning of the chronic phase and
      disappeared several months later. Mean serum sodium level was lower in the male
      group than in the female group throughout the clinical course. Mean serum levels
      of adrenaline and antidiuretic hormone were characterized by their prominent high
      value on the first day. Serum potassium levels were inversely related to serum
      levels of catecholamines, especially adrenaline, during the acute and subacute
      phases, particularly on the first day.

PMID- 15261231
TI  - Comparative study of pre-operative thymic imaging and pathology in patients with
      myasthenia gravis.
AB  - The objective of our study is to compare the diagnostic significance of
      mediastinal CT and (201)Tl-single-photon emission computed tomography (SPECT)
      with thymic histology in patients with myasthenia gravis (MG). The subjects were
      30 patients with MG who were scheduled to receive thymectomy. They did not
      receive immunosuppressive therapy. The mediastinal CT and (201)Tl-SPECT were
      performed before the thymectomy. As a consequence, 9 patients had thymoma, 11 had
      lymphoid follicular hyperplasia (LFH), and 10 had normal thymus on histologic
      examination after thymectomy. Retrospectively, CT diagnosed the histology of all
      9 patients with thymoma, and 5 of 11 with LFH. (201)Tl-SPECT could detect
      abnormal accumulations in only 6 of 9 cases of thymoma, and 6 of 11 cases of LFH.
      (201)Tl-SPECT could not distinguish thymoma from LFH. We conclude that a CT study
      is recommended as an essential study for the detection of thymic abnormalities in
      pre-operative patients with MG.

PMID- 15261232
TI  - Preliminary study of shunt related death in paediatric patients.
AB  - Hydrocephalus is a condition commonly encountered in paediatric and adult
      neurosurgery and cerebrospinal fluid (CSF) shunting remains the treatment of
      choice for many cases. Despite improvements in shunt technology and technique,
      morbidity and mortality remain. The incidence of early shunt obstruction is high
      with later failures seen less frequently. This review aims to examine mortality
      associated with mechanical failure of CSF shunts within Queensland. Neurosurgical
      and Intensive Care databases were reviewed for cases of mortality associated with
      shunt failure. Eight cases were identified between the years of 1992 and 2002
      with the average age at death 7.7 years. Deaths occurred on average 2 years after
      last shunt revision. Seven of the eight patients lived outside the metropolitan
      area. Shunting remains an imperfect means of treating hydrocephalus. Mortality
      may be encountered at any time post surgery and delays to surgical intervention
      influence this. Alternative measures such as third ventriculostomy or the
      placement of a separate access device should be considered. In the event of
      emergency, a spinal needle could be used to access the ventricle along the course
      of the ventricular catheter.

PMID- 15261233
TI  - Early electroencephalographic findings in patients with anoxic encephalopathy
      after cardiopulmonary arrest and successful resusitation.
AB  - This study investigated whether or not early electroencephalographic (EEG)
      findings and brain computed tomographic (CT) features reflect the prognosis of
      comatose patients for 48 h after cardiopulmonary resuscitation (CPR). EEGs and
      brain CT scans were collected from 21 patients within 72 h after CPR. The EEG
      findings were classified according to the five Hockaday grades. The Glasgow
      outcome scale (GOS) applied 3 months after CPR was used for prognosis. Of the
      nine patients with grade 1 and 2 EEGs, eight had a good outcome (five recovered
      satisfactorily and three remained moderately disabled). Of the eight patients
      with grade 4 and 5 EEGs, seven had a poor outcome (three died and four remained
      in a persistent vegetative state). On the other hand, there was no correlation
      between early CT features and prognosis except for two severe cases, one whose
      gray/white matter interface had disappeared and the other with relatively
      increased density of the thalami, brain stem and cerebellum. These findings
      suggest that EEG is more useful than CT scan as a diagnostic tool for anoxic
      encephalopathy after CPR.

PMID- 15261234
TI  - Diffusion weighted image negative transient ischaemic attack and reversible
      ischaemic neurological deficit. A report of 10 patients with complete recovery.
AB  - Diffusion-weighted magnetic resonance imaging (DWI MRI)-negative transient
      ischaemic attack (TIA) in hyperacute stroke is a well-known clinical entity.
      However, no precise analysis of this phenomenon has been reported. We identified
      10 patients with TIA or reversible ischaemic neurological deficits (RIND) with no
      focal hyperintensity on DWI MRI among 108 consecutive acute stroke patients who
      underwent DWI MRI. In these patients, we analysed the apparent diffusion
      coefficient (ADC) and determined the ipsilateral/contralateral ratio (IC ratio)
      to elucidate factors that may contribute to this phenomenon. Each patient also
      underwent simultaneous magnetic resonance angiography (MRA). The mean IC ratio in
      our study population was 0.976. Of the 10 patients, 7 had a proximal vascular
      stenosis on MRA. We discuss the pathophysiology underlying negative DWI MRI
      results in patients with TIA or RIND.

PMID- 15261236
TI  - Images in neuroscience. Wernicke's syndrome.

PMID- 15261235
TI  - Surgical experience with resection en bloc of intramedullary astrocytomas and
      ependymomas in the cervical and cervicothoracic region.
AB  - We performed 8 operations on 7 patients with benign intramedullary astrocytomas
      and ependymomas in the cervical and cervicothoracic region. All patients
      initially underwent gross total tumor resection en bloc. One patient with an
      astrocytoma showed tumor recurrence postoperatively, and underwent a second
      operation resulting in subtotal removal. The follow-up after the initial surgery
      ranged from 2.7 to 19.7 years (mean 8.5 years). Symptomatic improvement was
      observed in 6 patients after the initial operation. Two patients showed
      postoperative neurological deterioration, one with an ependymoma and the other
      after the second operation. No operative complications or deaths, nor
      postoperative respiratory dysfunction occurred. Benign intramedullary
      astrocytomas and ependymomas of the cervical and cervicothoracic spinal cord can
      be treated by radical resection en bloc with a low morbidity and recurrence, as
      well as acceptable outcomes. We describe here the surgical technique for en bloc
      tumor removal.

PMID- 15261237
TI  - The biocompatibility of BioGlue with the cerebral cortex: a pilot study.
AB  - An in vivo pilot study investigating the biocompatibility of BioGlue as a dural
      sealant is described. Craniotomies were performed in adult Wistar rats. After
      excising the dura, BioGlue was applied directly onto the cerebral cortex and
      sterile Surgicel (Ethicon Inc., Somerville, NJ) placed over the brain in control
      rats. All rats were culled 14 days post-surgery. An inflammatory cell infiltrate
      was found overlying the pia-arachnoid, but this did not extend into the brain
      parenchyma except in instances of mechanical disruption. Immunohistochemical
      staining for glial fibrillary acidic protein (GFAP) showed an increase in gliosis
      in the BioGlue treated rats but the degree of positive staining as well as the
      observed surface inflammation was not significant and possibly would not be
      clinically significant.

PMID- 15261238
TI  - Stent-graft placement in a traumatic internal carotid-internal jugular fistula
      and pseudoaneurysm.
AB  - Traumatic arteriovenous fistulas following carotid artery injuries are rare.
      Treatment of carotid artery-to-jugular vein fistula requires direct closure of
      the fistula or occlusion of the carotid artery above and below the level of the
      fistula, by a surgical or endovascular approach. A 32-year-old man presented with
      a right-sided pulsatile neck swelling 2 days following a stab wound. Neck
      computed tomography demonstrated a vascular mass protruding into the anterior
      neck. Digital subtraction arteriography demonstrated a bilobular large internal
      carotid artery pseudoaneurysm just distal to its bifurcation. There was
      simultaneous opacification of a dilated left internal jugular vein indicating a
      high-flow internal carotid-internal jugular fistula. A balloon-expandable stent
      graft was delivered and successfully positioned across the fistula. The
      arteriovenous fistula and pseudoaneurysm completely disappeared and the right
      internal carotid artery was well preserved. The stent-graft is a promising
      technology to obliterate fistulae and preserve the parent artery with relative
      safety.

PMID- 15261239
TI  - Juvenile pilocytic astrocytoma 'pilomyxoid variant' with spinal metastases.
AB  - We report a case of juvenile pilocytic astrocytoma of the hypothalamic/chiasmatic
      region with cerebrospinal fluid dissemination in a 16-month old girl. The tumour
      in this case had unusual histological features including the abundance of myxoid
      background, the absence of Rosenthal fibres and the presence of an angiocentric
      pattern. These features are consistent with the recently described "variant"
      named pilomyxoid astrocytoma. It remains unclear whether pilomyxoid astrocytoma
      represents an aggressive variant of classical juvenile pilocytic astrocytoma, or
      an entirely distinct clinico-pathological entity. Larger series and new molecular
      techniques may answer this question in the future.

PMID- 15261240
TI  - Intra-arterial thrombolysis in basilar artery occlusion and recent haemorrhagic
      stroke due to arteriovenous malformation.
AB  - We report the case of a young patient suffering from a severe ischaemic stroke
      due to basilar artery occlusion occurring during selective digital subtraction
      angiography. This examination was performed in order to assess an arteriovenous
      malformation in posterior cerebral artery territory responsible for haemorrhagic
      stroke occurring 17 days before. Intra-arterial thrombolysis with urokinase was
      performed and basilar artery recanalization was obtained 8 h after stroke onset.
      Despite the severe neurological impairment, the prolonged symptoms of ischaemia
      and the high bleeding risk due to the recent cerebral haemorrhage in the same
      vascular territory involved in thrombolysis, the treatment determined a very
      favourable clinical outcome.

PMID- 15261241
TI  - Neuromagnetic separation of secondarily bilateral synchronized spike foci: report
      of three cases.
AB  - To demonstrate the high spatiotemporal resolution of magnetoencephalography
      (MEG), we report three cases with focal epilepsy that exhibited bilateral
      synchronized spikes on simultaneous scalp EEG and MEG recording. Constant time
      lags (19.4 +/- 3.0 ms and 20.0 +/- 5.5) between the leading and the following
      contralateral spikes were noted on MEG and the current dipole sources were
      localized in the bilateral homotopic regions symmetrically in Cases 1 and 3. In
      Case 2, MEG indicated leading spikes in the left frontal region, with a time lag
      of 42.3 +/- 8.4 ms to reach the contralateral frontal and bilateral temporal
      regions as well. Chronic subdural EEG recording in Cases 1 and 2 confirmed that
      the leading spike focus in MEG was close to the seizure onset zone in cortical
      EEG. Spatio-temporal analysis of MEG spikes may be useful to identify the primary
      epileptic region in patients with synchronized bilateral epileptiform discharges.

PMID- 15261242
TI  - A discrepancy between Tc-99m HMPAO SPECT and Tc-99m ECD SPECT in Creutzfeldt
      Jacob disease.
AB  - We observed a discrepancy between the perfusion patterns seen in single photon
      emission computed tomography (SPECT) images obtained using technetium-99m
      hexamethyl propylene amine oxime (HMPAO) and SPECT images obtained using
      technetium-99m ethyl cysteinate dimer (ECD) in an 84-year-old man with
      Creutzfeldt-Jacob disease (CJD). HMPAO-SPECT demonstrated a reduction in
      perfusion in the parieto-temporal regions, especially the left temporal area.
      However, ECD-SPECT revealed a significant reduction in the bifrontal regions. At
      autopsy, the characteristic pathological findings of CJD, spongiform vacuolation,
      were most prominent in the bifrontal regions. Thus, the clinical features and the
      pathological findings were more closely correlated with the ECD-SPECT images than
      the HMPAO-SPECT images.

PMID- 15261243
TI  - Gliosarcoma with osteosarcomatous differentiation: review of radiological and
      pathological features.
AB  - Gliosarcoma is a rare tumor of the central nervous system, consisting of
      gliomatous and sarcomatous elements. We present an unusual case of gliosarcoma
      which demonstrated a variation in phenotype over a six month period, changing
      from a gliosarcoma with osteosarcomatous differentiation, to a gliosarcoma with
      no osteosarcomatous component. The initial histological diagnosis was
      glioblastoma multiforme. Fifteen months later the tumor had transformed into a
      gliosarcoma demonstrating osteosarcomatous differentiation, with the majority of
      the tumor consisting of osteoid matrix. Further samples taken six months later
      revealed gliosarcoma with almost no osteosarcomatous component. It is recognized
      that glioblastoma can undergo a change in phenotype, transforming into a
      gliosarcoma. This case demonstrates that ongoing changes in phenotype can occur,
      especially when the tumor has been treated with chemotherapy and radiotherapy. An
      understanding of the pathological progression of gliosarcoma will become
      increasingly important as novel treatments for gliosarcoma and glioblastoma
      become available.

PMID- 15261244
TI  - Factors affecting haemorrhagic transformation in middle cerebral artery
      infarctions.
AB  - OBJECTIVE: Haemorrhagic transformation (HT) affects treatment and prognosis in
      patients with acute ischaemic stroke. The factors affecting haemorrhagic
      transformation in infarcts due to occlusion of middle cerebral artery (MCA) stem
      or branch were investigated. MATERIALS AND METHODS: Of 412 patients who were
      followed in our clinic between January 2001 and December 2001 with acute
      ischaemic stroke, 86 patients with occlusion in MCA stem or branch were enrolled
      in this study. These patients were divided into 2 groups, those with HT (n = 35)
      and without HT (n = 51). Age, sex, systemic arterial hypertension, diabetes
      mellitus, blood glucose level in the acute period, renal and liver function
      tests, systolic and diastolic arterial blood pressure in the acute period,
      previous cerebrovascular disease, leukoaraiosis, modified Rankin Disability Score
      (mRDS) and stroke subtype were evaluated. RESULTS: High blood glucose level in
      the acute period and presence of leukoaraiosis on cranial computerized (CCT)
      tomography were detected as risk factors in development of HT. HT was seen more
      frequently in MCA stem infarction than branch infarction. mRDS were worse in the
      group with HT. In multivariate analysis, there were independent relationships
      between mean blood glucose level on admission, mRDS, presence of diabetes
      mellitus, and MCA stem infarction and development of haemorrhagic transformation
      in patients with MCA territorial infarction.

PMID- 15261245
TI  - Acute ophthalmoplegia with pupillary areflexia associated with anti-GQ1b
      antibody.
AB  - Raised anti-GQ1b antibody is associated with Miller Fisher syndrome, Guillain
      Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff's brain stem encephalitis,
      acute ophthalmoparesis without ataxia and ataxic GBS without opthalmoplegia. We
      report a rare case of acute ophthalmoplegia associated with anti-GQ1b antibody
      that also had pupillary areflexia. A 35-year-old Chinese lady presented with
      external ophthalmoplegia, pupillary areflexia and no other abnormalities of
      cranial nerves, muscle tone, deep tendon reflexes, limb power or cerebellar
      dysfunction. Anti-GQ1b IgG antibody titre was significantly elevated, while
      neuroimaging of brain and orbital structures, nerve conduction study and cerebral
      spinal fluid examination were normal. Pupillary areflexia should be recognized as
      another feature that may be present in conditions associated with raised anti
      GQ1b antibody.

PMID- 15261246
TI  - Longitudinal clivus fracture associated with trapped basilar artery: unusual
      survival with good neurological recovery.
AB  - A 46-year-old motorcyclist sustained severe cranio-facial fractures from a fall
      at 60 km/h. He gradually developed a left hemiparesis and diplopia but retained a
      GCS of 15. CT head scan revealed a longitudinal clivus fracture. MRA of
      intracranial vessels identified a trapped basilar artery. The patient made an
      excellent recovery with residual left abducens palsy on follow-up at 10 weeks.
      Such recovery with minimal residual deficit in the context of this injury has not
      previously been reported. Reported cases to date are reviewed and causative
      mechanisms discussed.

PMID- 15261247
TI  - Subfrontal schwannoma: a case report and literature review.
AB  - Subfrontal schwannomas are rare and usually misdiagnosed preoperatively. We
      present the third reported case of a schwannoma arising from the olfactory nerve.
      The neuroradiological and pathological features of the case, as well as the
      origin of the tumour are discussed.

PMID- 15261248
TI  - A lumbar clear cell meningioma with foraminal extension in a renal transplant
      recipient.
AB  - Spinal meningiomas are characteristically dural based. We report a lumbar clear
      cell meningioma extending into the intervertebral foramen without dural
      attachment which mimics a neurilemmoma. This is a rare finding, with no other
      reported cases in the literature. The importance of recognizing clear cell
      meningioma relates specifically to its inordinately aggressive clinical course.
      Compared to with of spinal clear cell meningiomas reported to date, our case
      showing the extension into the intervertebral foramen and mimicking a
      neurilemmoma is rather unique. Clear cell meningioma may be confused with other
      clear cell tumors, especially with the similar-looking metastatic renal cell
      carcinoma, which should be carefully ruled out in our case - an immunosuppressed
      renal transplant recipient.

PMID- 15261249
TI  - Successful conservative operative management of pineal apoplexy.
AB  - A 71-year-old woman presented with obstructive hydrocephalus caused by a
      haemorrhagic pineal mass. A right ventriculo-peritoneal shunt was inserted with
      successful treatment of the hydrocephalus and resolution of symptoms and signs.
      Post-operative MRI both as an inpatient and at 5 and 18 months showed no contrast
      enhancement of the lesion and there was resolution of the radiographic
      abnormality. She remains symptom-free at 18 months. Previous reports have
      advocated resection of the pineal lesion, but this patient has done well with CSF
      shunting and MRI surveillance.

PMID- 15261250
TI  - Transient global amnesia in a patient with acute unilateral caudate nucleus
      ischemia.
AB  - The pathogenesis and localization of neuronal dysfunction in transient global
      amnesia (TGA) is still disputed more than 40 years after the first description of
      this clinical entity. Previous studies have indicated that structural abnormality
      is rare in TGA. We report a case of TGA in a patient with acute ischemia in the
      body of right caudate nucleus. This provides evidence in support of an ischemic
      hypothesis as the possible etiology of TGA. The role of caudate nucleus in human
      memory is also reviewed.

PMID- 15261251
TI  - Syringomyelia-like manifestation of subacute combined degeneration.
AB  - A 32-year-old male presented with progressive weakness and numbness of both upper
      limbs of one-month duration. The patient had weakness and wasting of small
      muscles of both hands with weak grip. Sensory system revealed graded sensory loss
      to pain, temperature and touch in C5 to T1 distribution and vibration and joint
      position sense from C5 to C8 in the both upper limbs. There was areflexia in the
      upper limbs while there was no motor or sensory deficit in the lower limbs. The
      cortical potential on stimulation of posterior tibial nerve was prolonged on both
      sides. On MR imaging of the cervical spine there was iso to low intense lesion
      which was hyperintense on T2-weighted imaging along the dorsal aspect of the cord
      extending from C2 to C6 level. The axial images showed involvement of the
      posterior column. The serum vitamin B12 level was found to be low. The patient
      responded to parenteral cyanocobalamine therapy and the radiological lesion
      subsequently resolved.

PMID- 15261252
TI  - C2 over C3 spondyloptosis in a case with absent posterior elements. Report of an
      unusual case and analysis of treatment options.
AB  - We report an extremely rare anomaly in a 31-year-old male patient, where the
      posterior elements of the axis were almost completely absent and the anterior
      elements were dislocated anterior to the body of the C3 vertebra. The body of C3
      caused severe compression of the high cervical cord. A radical transoral
      decompression and plate and screw fixation resulted in sustained clinical
      improvement. The relevant literature is briefly reviewed and the treatment
      options in such a case are analyzed.

PMID- 15261253
TI  - Propionibacterium acnes causing delayed subdural empyema - a case report and
      review of literature.
AB  - The authors report a patient who presented with a delayed subdural empyema caused
      by Propionibacterium acnes following excision of a meningioma. This organism
      should be suspected in all patients with delayed empyema especially in the
      presence of implants and immunosuppression. The main features of this pathogen is
      discussed. Surgical drainage and high-dose intravenous penicillin should be the
      recommended therapy.

PMID- 15261254
TI  - Preoperative visualization of microvascular compression of cranial nerve IX using
      constructive interference in steady state magnetic resonance imaging in
      glossopharyngeal neuralgia.
AB  - We report a case of successfully treated glossopharyngeal neuralgia, in whom
      preoperative magnetic resonance imaging (MRI) with a sequence of constructive
      interference in steady-state (CISS) precisely delineated microvascular
      compression to the glossopharyngeal nerve at its cisternal portion. A 70-year old
      female experienced paroxysmal and excruciating pain, starting in the right ear
      and descending to the tongue and throat. The pain was brief, burning and
      triggered by swallowing food and drinks. Preoperative CISS-MRI delineated a small
      vascular loop compressing the glossopharyngeal nerve at its cisternal portion.
      The patient was diagnosed with glossopharyngeal neuralgia, and then,
      microvascular decompression surgery was performed. Intraoperative inspection
      revealed that the glossopharyngeal nerve root was in contact with a small
      arterial loop at its cisternal portion and was deformed as demonstrated by
      preoperative CISS-MRI. The glossopharyngeal nerve was displaced using a piece of
      Teflon felt, freeing it from the arterial loop compression. The patient's
      neuralgia resolved immediately after surgery. During a period of 2-years follow
      up, no recurrence of the neuralgia has occurred. The usefulness of CISS-MRI for
      the diagnosis of glossopharyngeal neuralgia is discussed.

PMID- 15261255
TI  - In vitro monitoring of nanogram levels of puerarin in human urine using flow
      injection chemiluminescence.
AB  - A rapid and sensitive chemiluminescence (CL) determination of puerarin with the
      flow injection technique was presented. It was found that puerarin could enhance
      the CL generated from luminol-KIO(4) system significantly. The increment of CL
      intensity was linear over the concentration of puerarin ranging from 0.3 to 100.0
      ng mL(-1) (r(2)=0.9963), offering a detection limit as low as 0.1 ng mL(-1) (3
      sigma). At a flow rate of 2.0 mL min(-1), one analysis cycle, including sampling
      and washing, could be accomplished in 20 s with a relative standard deviation of
      less than 5.0%. The experimental results demonstrated that the excretive amounts
      of puerarin reached its maximum in 3 h after taking 250 mL green drink containing
      275 mg puerarin, and the puerarin excretive ratio during 24 h was 9.70% in the
      body of volunteers.

PMID- 15261256
TI  - Design and synthesis of cyclic urea compounds: a pharmacological study for
      retinoidal activity.
AB  - Retinoids are natural and synthetic analogues of all-trans retinoic acid (ATRA).
      Cancer and other serious hyperproliferative diseases are attractive therapeutic
      targets for retinoids. We report here the design and synthesis of novel cyclic
      urea compounds with retinoidal activity. YR105 exhibited potent differentiation
      inducing ability toward human promyelocytic leukemia HL-60 cells at the
      concentration of 10(-9)M: its potency was almost equal to that of the native
      ligand, all-trans retinoic acid.

PMID- 15261257
TI  - Synthesis and biological evaluation of novel 4"-alkoxy avermectin derivatives.
AB  - Novel 4"-alkoxy avermectin derivatives were synthesized via rhodium carbenoid
      mediated O-H insertion reaction and tested for antiparasite activity against
      Artemia salina and Caenorhabditis elegans.

PMID- 15261258
TI  - Phenylhomophthalimide-type NOS inhibitors derived from thalidomide.
AB  - Thalidomide shows moderate inhibitory activity toward neuronal nitric oxide
      synthase (nNOS) and inducible NOS (iNOS), but not toward endothelial NOS (eNOS).
      Structural development studies of thalidomide yielded novel phenylhomophthalimide
      type NOS inhibitors with enhanced activity and different subtype selectivity.

PMID- 15261259
TI  - Benzodiazepine inhibitors of the MMPs and TACE. Part 2.
AB  - A series of benzodiazepine MMP/TACE inhibitors bearing polar moieties has been
      synthesized in an effort to optimize inhibitory activity against LPS-stimulated
      TNF production in human monocytes and oral activity in a murine LPS model.

PMID- 15261260
TI  - Rapid cleavage of cyclic tertiary amides of Kemp's triacid: effects of ring
      structure.
AB  - The piperidyl and prolyl amides of Kemp's triacid (7 and 8, respectively) have
      been prepared and their rates of intramolecular acylolysis measured as a function
      of pD. The piperidyl derivative 7 reacts approximately four-times faster (e.g.,
      t(1/2)=3 min at 20 degrees C and pD7.7) than the previously reported pyrrolidyl
      and methylphenethyl amide derivatives, while the prolyl derivative 8 reacts two
      times more slowly (e.g., e.g., t(1/2)=30 min at 20 degrees C and pD7.8).
      Molecular-mechanics calculations indicate that the nonbonded interactions in the
      piperidyl derivative 7 are distinct from those in the prolyl, pyrrolidyl, and
      methylphenethyl amide derivatives, a result that supports the suggestion that
      ground-state pseudoallylic strain contributes to the enormous reactivity of
      Kemp's triacid tertiary amides. In sum, the results reported indicate that the
      Kemp's triacid scaffolding provides a general means of activating tertiary amide
      derivatives.

PMID- 15261261
TI  - Thiourea inhibitors of herpesviruses. Part 3: Inhibitors of varicella zoster
      virus.
AB  - The preparation of alpha-methylbenzyl thioureas and their biological activity
      against varicella zoster virus is described. Several analogs demonstrated
      IC50s<0.1 microM and their SAR are discussed. These compounds represent a novel
      class of potent and selective nonnucleoside inhibitors of varicella zoster virus.

PMID- 15261262
TI  - Low molecular weight thrombin inhibitors with excellent potency, metabolic
      stability, and oral bioavailability.
AB  - Modification of lead compound 1 by reducing lipophilicity in the P3 group
      produced a series of low molecular weight thrombin inhibitors with excellent
      potency in functional assays, metabolic stability, and oral bioavailability.
      These modifications led to the identification of two optimized compounds, 14 and
      16.

PMID- 15261263
TI  - Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based
      adenosine kinase inhibitors.
AB  - Three new approaches have been tested to modify existing pyridopyrimidine and
      alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4
      Amino-substituted pteridines 8a-e were generally less active than corresponding 5
      and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC(50)=7.5 nM
      was superior to its open chain alkynylpyrimidine analog 13g (IC(50)=22 nM) while
      pyrrolopyrimidines such as 17a were inactive.

PMID- 15261264
TI  - Optimization and metabolic stabilization of a class of nonsteroidal
      glucocorticoid modulators.
AB  - The optimization of a series of nonsteroidal glucocorticoid modulators is
      reported. Potent selective GR ligands that have improved metabolic stability were
      discovered typified by the subnanomolar acid 12 (GR binding IC(50)=0.6 nM).

PMID- 15261265
TI  - Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid
      receptor modulator-statin hybrids.
AB  - The synthesis, activity, metabolic stability, and pharmacokinetics of steroidal
      and nonsteroidal glucocorticoid receptor modulator-statin hybrids is reported.
      Potent steroidal antagonist-statin hybrids like 22 (h-GR binding IC(50)=7 nM) and
      nonsteroidal modulator hybrids like 16 (h-GR binding IC(50)=2 nM) were
      discovered. Appending a 'statin'-like diol-acid group to the modulators
      dramatically improved metabolic stability (and in some cases hepatocyte
      activity), but did not impart hepatoselectivity.

PMID- 15261266
TI  - Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator.
AB  - Bile acid conjugates of a selective nonsteroidal glucocorticoid receptor
      modulator were prepared and evaluated. Potent GR binding conjugates that showed
      improved metabolic stability were discovered. However, cellular potency and
      pharmacokinetics were not substantially improved.

PMID- 15261267
TI  - Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as
      potential antimicrobial agents.
AB  - A number of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives were synthesized and
      screened for antibacterial and antifungal activities. All the synthesized
      compounds showed the potent antimicrobial activity. The quantitative structure
      activity relationship investigation was applied to find a correlation between the
      different physicochemical parameters of the compounds studied and their
      biological activity.

PMID- 15261268
TI  - Factor Xa inhibitors based on a 2-carboxyindole scaffold: SAR of neutral P1
      substituents.
AB  - A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is
      described. Structural requirements for neutral ligands, which bind in the S1
      pocket of factor Xa were investigated with the 2-carboxyindole scaffold. This
      privileged fragment assembly approach yielded a set of equipotent, selective
      inhibitors with structurally diverse neutral P1 substituents.

PMID- 15261269
TI  - Novel factor Xa inhibitors based on a 2-carboxyindole scaffold: SAR of P4
      substituents in combination with a neutral P1 ligand.
AB  - A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is
      described. Structural requirements for P4 ligands in combination with a neutral
      biaryl P1 ligand were investigated with the 2-carboxyindole scaffold. A diverse
      set of P4 substituents was identified, which, in conjunction with a biaryl P1
      ligand, gave highly potent factor Xa inhibitors, which were also selective versus
      other proteases and efficacious in various antithrombotic secondary assays.

PMID- 15261270
TI  - Copper dipicolinates as peptidomimetic ligands for the Src SH2 domain.
AB  - The introduction of copper chelates into peptide mimetics creates the Src SH2
      binding ligands and paramagnetic complexes suitable for EPR studies of peptide
      protein interactions. The dipicolinic acid was attached to SH2 domain targeting
      fragments by two different linkers.

PMID- 15261271
TI  - Amino porphyrins as photoinhibitors of Gram-positive and -negative bacteria.
AB  - Twenty four aminoporphyrin derivatives have been tested in vitro for their
      antibacterial photoactivity against Escherichia coli and Staphylococcus aureus.
      Two of these compounds, bearing polyamine units, exhibited a significant activity
      especially against Gram-negative bacteria (E. coli).

PMID- 15261272
TI  - Synthesis of 7 alpha- and 7 beta-spermidinylcholesterol, squalamine analogues.
AB  - Stereoselective synthesis of squalamine dessulfates analogues, 7 alpha and 7 beta
      N-[3N-(4-aminobutyl) aminopropyl]aminocholesterol are reported, using 7 alpha and
      7 beta-aminocholesterol as a key intermediate. It's the first example in which
      the position of spermidine is modified at the steroid ring. These molecules
      showed a comparable antibacteria and fungi activities to squalamine. Then, they
      have a cytotoxic activity on a human non-small cell bronchopulmonary carcinoma
      line (NSCLC-N6).

PMID- 15261273
TI  - Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data.
AB  - Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that
      catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use
      in determining the role of Epi in the central nervous system. Here we demonstrate
      that a routinely used assay for screening PNMT inhibitors is not appropriate for
      those inhibitors having K(i) values less than 1 microM. A revised assay has been
      developed that shows some inhibitors bind two orders of magnitude more tightly
      than previously reported.

PMID- 15261274
TI  - Identification of [(naphthalene-1-carbonyl)-amino]-acetic acid derivatives as
      nonnucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase.
AB  - A novel series of HCV NS5B RNA dependent RNA polymerase inhibitors containing a
      naphthalene carboxamide scaffold were identified by high throughput screening.
      Optimization of substituents by parallel synthesis and the iterative design
      towards understanding structure-activity relationship to improve potency are
      described. Tetra substituted naphthalene 31 displayed potent activity with IC(50)
      of 120 nM against HCV NS5B enzyme and was selective over a panel of polymerases.

PMID- 15261275
TI  - Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2
      (OX(2)R) antagonists.
AB  - Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A
      and B) interacting with two known G-protein coupled receptors (OX(1)R and
      OX(2)R). In addition to other biological functions, the orexin-2 receptor is
      thought to be an important modulator of sleep and wakefulness. Herein we describe
      a series of novel, selective OX(2)R antagonists consisting of substituted 4
      phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3
      ((4S,5S)-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea, which is bound by the
      OX(2)R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the
      OX(2)R over the OX(1)R.

PMID- 15261276
TI  - Bis-quinolinium cyclophanes: toward a pharmacophore model for the blockade of
      apamin-sensitive SKCa channels in sympathetic neurons.
AB  - The synthesis, pharmacological evaluation, and molecular modeling studies of
      unsymmetrical bis-alkylene bis-quinolinium cyclophanes and xylylene-alkylene bis
      quinolinium cyclophanes is described. Two important structural features of the
      pharmacophore for SK(Ca) channel blockade have been identified. These are (i) an
      optimum distance of ca. 5.8A between the centroids of the pyridinium rings of the
      two quinolinium groups and (ii) a preference for conformations having the
      quinolinium groups in a synperiplanar orientation.

PMID- 15261277
TI  - Synthesis and biological activity of 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine CDK
      inhibitors.
AB  - A series of 2-anilino-4-(1H-pyrrol-3-yl)pyrimidines were prepared and evaluated
      for their ability to inhibit cyclin-dependent kinases (CDKs). A number of
      analogues were found to be potent CDK2 and CDK4 inhibitors and to exhibit anti
      proliferative activity against human tumour cell lines. Structure-activity
      relationships and biochemical characterization are presented.

PMID- 15261278
TI  - Rational drug design and synthesis of a selective opioid receptor antagonist on
      the basis of the accessory site concept.
AB  - To newly synthesize a selective opioid receptor antagonist, 17
      (cyclopropylmethyl)-4,5 alpha-epoxy-6 beta,21-epoxymethano-3-hydroxy-6,14
      endoethenomorphinan-7 alpha-(N-phenethyl)carboxamide was first designed from an
      opioid receptor agonist TAN-821 on the basis of the accessory site concept. The
      designed compound antagonized the agonistic effects induced by an opioid receptor
      agonist beta-endorphin on the rat vas deference test. Moreover, the designed
      compound blocked the antinociception induced by beta-endorphin given
      intracerebroventricularly.

PMID- 15261279
TI  - Aminotriazine 5-HT7 antagonists.
AB  - The present studies have identified a series of aminotriazines as novel 5-HT(7)
      receptor antagonists. Compounds 10 and 17 have high affinity for the 5-HT(7)
      receptor and do not bind to either the 5-HT(2C) or 5-HT(6) receptors. These
      compounds produce no agonist effects by themselves, and shift the dose-response
      curve of 5-CT to the right in the manner of an antagonist.

PMID- 15261280
TI  - Diaminopyrimidine and diaminopyridine 5-HT7 ligands.
AB  - The present studies have identified a series of diaminopyrimidines and
      diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes
      of pyrimidines and four regioisomeric classes of pyridines were synthesized and
      analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of
      different regioisomers show clearly the structure-activity relationship with
      position of ring nitrogens.

PMID- 15261281
TI  - Novel (3,5-di-tert-butyl-2-hydroxy-phenylcarbamoyl)-alkanoic acids as potent
      antioxidants.
AB  - A series of novel phenolic antioxidants of amphiphilic structure has been
      synthesized. Investigations into the influence of aliphatic spacer length and
      nature of a hydrophilic anchor on the antioxidant activity allowed elucidating
      certain structure requirements for the membrane-addressed antioxidant designing.

PMID- 15261282
TI  - Structure-activity relationships of methylene or terminal side chain modified
      retinoids on the differentiation and cell death signaling in NB4 promyelocytic
      leukemia cells.
AB  - New structure-activity relationships of a series of methylene or side chain
      modified retinoids on NB4 acute promyelocytic leukemia cells are investigated.
      The differentiation- and apoptosis-inducing potential of these compounds is
      analyzed on the basis of their selective retinoic acid receptor binding profile.

PMID- 15261283
TI  - Pharmacological evaluation of selected arylpiperazines with atypical
      antipsychotic potential.
AB  - Six active compounds, among previously synthesized and screened arylpiperazines,
      were selected and evaluated for the binding affinity to rat dopamine, serotonin
      and alpha(1) receptors. Two compounds with benztriazole group had a 5-HT(2A)/D(2)
      binding ratio characteristic for atypical neuroleptics (>1, pK(i) values).
      Compound 2, 5-[2-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]ethyl]1H-benzotriazole,
      expressed clozapine-like in vitro binding profile at D(2), 5-HT(2A) and alpha 1
      receptors and a higher affinity for 5-HT(1A) receptors than clozapine. Also, it
      exhibited the noncataleptic behavioural pattern of atypical antipsychotics and
      antagonized d-amphetamine-induced hyperlocomotion in rats.

PMID- 15261284
TI  - The development of novel inhibitors of tumor necrosis factor-alpha (TNF-alpha)
      production based on substituted [5,5]-bicyclic pyrazolones.
AB  - Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of
      tumor necrosis factor-alpha (TNF-alpha) production. Many of these compounds show
      low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-alpha
      production in THP-1 cells. This class of molecules was co-crystallized with
      mutated p38, and several analogs showed good oral bioavailability in the rat.
      Oral activity of these compounds in the rat iodoacetate model for osteoarthritis
      is discussed.

PMID- 15261285
TI  - The beta-glucuronyl-based prodrug strategy allows for its application on beta
      glucuronyl-platinum conjugates.
AB  - The use of platinum drugs in antitumour therapy is well established. An important
      drawback of these chemotherapeutics is the lack of selectivity for tumour cells,
      usually resulting in severe toxic side effects. A glucuronyl-platinum conjugate
      was designed and synthesised to test the compatibility of platinum compounds with
      beta-glucuronidase-based prodrug therapy. Instantaneous cleavage of the beta
      glucuronic bond in the glucuronyl-platinum conjugate was observed upon addition
      of beta-glucuronidase resulting in Pt(II)(dach)(4-hydroxybenzylmalonate) and
      glucuronic acid.

PMID- 15261286
TI  - Acyl-CoA: cholesterol acyltransferase inhibitory activities of fatty acid amides
      isolated from Mylabris phalerate Pallas.
AB  - Unsaturated fatty acid amides, 9(Z)-octadecenamide (2) and 9(Z),12(Z)
      octadecadienamide (4) as inhibitors of acyl-CoA: cholesterol acyltransferase
      (ACAT) were isolated from the ethyl acetate extracts of the insect, Mylabris
      phalerate Pallas, and elucidated by their spectroscopic data analysis. Compounds
      2 and 4 inhibited rat liver microsomal ACAT, hACAT-1, and hACAT-2 with IC(50)
      values of 170, 85, and 63 microM for 2 and of 151, 53, and 45 microM for 4,
      respectively.

PMID- 15261287
TI  - Structure-activity relationships of potent and selective factor Xa inhibitors:
      benzimidazole derivatives with the side chain oriented to the prime site of
      factor Xa.
AB  - A series of benzimidazole derivatives with the side chain on the nitrogen atom
      oriented to the prime site of factor Xa (FXa) were designed and synthesized.
      Compounds with substituted aminocarbonylmethyl groups as the side chain showed
      potent FXa inhibitory activity. Compounds 1 and 2 exhibited most potent
      inhibitory activity and were effective as anticoagulants in a DIC model.

PMID- 15261288
TI  - Antioxidative activities of novel diphenylalkyl piperazine derivatives with high
      affinities for the dopamine transporter.
AB  - A new series of diphenylalkyl piperazine derivatives with high affinities for the
      dopamine transporter (DAT), which were modified at both the diphenylalkyl moiety
      and the phenyl ring in the phenylamino moiety of 1-[4,4-bis(4-fluorophenyl)butyl]
      4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1, was evaluated for their
      inhibitory activities against auto-oxidative lipid peroxidation in canine brain
      homogenates. Some of these were approximately equivalent in activity to alpha
      tocopherol as a potent antioxidant with IC(50) values of low micromolar order,
      and the 4-hydroxyphenyl derivative 11 showed the most potent antioxidative
      activity with an IC(50) value of 0.32 microM, exhibiting approximately 5-fold
      more potent activity than alpha-tocopherol. The structure-activity relationship
      (SAR) studies of the antioxidative activity of these derivatives are presented.

PMID- 15261289
TI  - Rational design of potent and selective NH-linked aryl/heteroaryl cathepsin K
      inhibitors.
AB  - Prior reports from our laboratories have identified the nonpeptidic inhibitor 2
      as a potent and selective Cathepsin K (Cat K) inhibitor. Modelling studies
      suggested that the introduction of a NH linker between the P3 aryl and P2
      leucinamide moieties would allow the formation of a H-bond with the Gly66 residue
      of Cat K, hopefully increasing potency. Aniline 4 was thus synthesized and showed
      improved potency over its predecessor 2. Further modelling concluded that a 2
      substituted five membered ring could more adequately place the P3 moiety of 4
      into the S3 pocket of Cat K. The synthesis of the 2-substituted thiophene 5
      confirmed this hypothesis by displaying a slight increase in potency against Cat
      K (>10-fold increase in potency vs 2) and a good selectivity profile against
      Cathepsins B, L, and S. This rationally designed inhibitor 5 also displayed
      increased potency in a functional bone resorption assay (10nM) versus 2 (95 nM).

PMID- 15261290
TI  - A unidirectional crosslinking strategy for HIV-1 protease dimerization
      inhibitors.
AB  - A novel strategy to identify potent HIV-1 protease dimerization inhibitors was
      developed using 12-aminododecanoic acid as a tether to crosslink interfacial
      peptides. The directionality of the southern peptide was changed from N-->C to C-
      >N as compared to previously reported inhibitors. The terminal amine of the
      southern peptide and side chains were further diversified to find essential
      functional groups for dimerization inhibition of HIV-1 protease.

PMID- 15261291
TI  - Alpha,alpha-difluoro-beta-ketophosphonates as potent inhibitors of protein
      tyrosine phosphatase 1B.
AB  - A novel series of inhibitors that contain an aryl alpha,alpha-difluoro-beta
      ketophosphonate group has been synthesized and evaluated against protein tyrosine
      phosphatase 1B. These compounds exhibit strong inhibitory activity, the best of
      which has a K(i) value of 0.17 microM. These results demonstrate that aryl
      alpha,alpha-difluoro-beta-ketophosphonates are powerful phosphotyrosine mimetics
      for the development of potent PTP inhibitors.

PMID- 15261292
TI  - Synthesis and structure-activity relationships of 3,5-diarylisoxazoles and 3,5
      diaryl-1,2,4-oxadiazoles, novel classes of small molecule interleukin-8 (IL-8)
      receptor antagonists.
AB  - A novel series of 3,5-diarylisoxazole and 3,5-diaryl-1,2,4-oxadiazole IL-8
      inhibitors has been identified. These compounds exhibit activity in an IL-8
      binding assay as well as in a functional assay of IL-8 induced elastase release
      from neutrophils. In addition, one of the compounds exhibits oral activity in a
      rat adjuvant arthritis model.

PMID- 15261293
TI  - Molecular mechanisms of adefovir sensitivity and resistance in HBV polymerase
      mutants: a molecular dynamics study.
AB  - Molecular modeling studies of adefovir diphosphate with the wild type and the
      mutant HBV polymerase-DNA complex demonstrated that the increase in adefovir
      sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I)
      is a result of increased van der Waals interaction and is supplemented by the
      decreased affinity of natural substrate toward the mutant HBV polymerase. In the
      case of rtN236T mutant, loss of two hydrogen bonds accompanied by significant
      decrease in electrostatic interactions is observed, which explains the observed
      decrease in drug sensitivity and binding affinity of adefovir diphosphate toward
      the rtN236T mutant HBV polymerase.

PMID- 15261294
TI  - Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived
      indoloazepine.
AB  - The marine sponge metabolite hymenialdisine is a potent inhibitor of a variety of
      kinases including MEK-1, GSK-3 beta, and CK1. In addition, hymenialdisine and
      debromohymenialdisine exhibit inhibition of the G(2) cell cycle checkpoint at
      micromolar concentrations. We report herein the potent inhibition of cell cycle
      kinase Chk2 by the indolic-hymenialdisine indoloazepine 1 (IC(50)=8 nM).

PMID- 15261295
TI  - Monoclonal antibody mediated intracellular targeting of tallysomycin S(10b).
AB  - The potency of tallysomycin S(10b) (TLM S(10b)) an analogue bleomycin was
      enhanced by up to 875-fold when it was conjugated to the internalizing antibody
      BR96. Attachment to the antibody is achieved via a Cathepsin B cleavable linker.
      The enhancement in potency is believed to be a result of cellular uptake of the
      conjugate upon antigen binding followed by rapid release of the drug inside the
      lysosome. This method provides a novel approach for increasing the potency and
      therapeutic index of nominally moderately-active cytotoxic agents.

PMID- 15261296
TI  - Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B
      segment heterosubstituents.
AB  - Modifications of the B-segment of HTI-286 (2) produced a class of analogs
      incorporating heteroatom-substituents. The structure-activity relationship was
      studied. Analogs bearing methylsulfide and fluoride groups exhibited potency
      comparable to that of the parent compound HTI-286 and to paclitaxel in
      cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent
      than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines.
      Several analogs showed strong inhibition of tubulin polymerization.

PMID- 15261297
TI  - P4 cap modified tetrapeptidyl alpha-ketoamides as potent HCV NS3 protease
      inhibitors.
AB  - We describe herein the design, syntheses, and biological evaluation of new series
      of P4 tetrazole and adipic acid, ester, amide capped tetrapeptidyl alpha
      ketoamide based HCV protease inhibitors.

PMID- 15261298
TI  - Design and synthesis of novel Cdc25A-inhibitors having phosphate group as a
      hydrophilic residue.
AB  - Compounds (6a-e) were synthesized by phosphorylation of hydrophobic perhydroindan
      derivatives derived from vitamin D(3), and were found to show strong inhibitory
      activity towards dual-specificity phosphatase Cdc25A (IC(50)=0.7-24.5 microM).

PMID- 15261299
TI  - Synthesis of an immunosuppressant SQAG9 and determination of the binding peptide
      by T7 phage display.
AB  - SQAG9, a new class of immunosuppressive sulfoquinovosylacylglycerol, and its
      biotinylated derivatives have been synthesized. A T7 Phage library, composed of
      random cDNA fragments from Drosophila melanogaster, displayed a possible binding
      peptide of 14 amino acids. The immobilized synthetic peptide on a sensor chip
      showed a dissociation constant of K(D)=1.5 x 10(-6) against SQAG9 in a surface
      plasmon resonance experiment.

PMID- 15261300
TI  - Synthesis, biophysical and biological evaluation of 3,6-bis-amidoacridines with
      extended 9-anilino substituents as potent G-quadruplex-binding telomerase
      inhibitors.
AB  - Telomerase and telomere maintenance are emerging targets for the treatment of
      human cancers. We report here on the targeting of the telomere-telomerase complex
      with a series of small molecules based on an acridine platform. A series of 3,6
      bisamidoacridines with extended 9-anilino sidechains were designed and
      synthesised as potential telomeric G-quadruplex DNA (G4) interacting compounds.
      G4-stabilisation was assessed using a high-throughput FRET (fluorescence
      resonance energy transfer) assay and telomerase inhibition quantified by a
      modified TRAP (telomerase repeat amplification protocol) method. Within the
      series, the compounds showed significant G4-stabilising ability (Delta T(m)
      values of 25-36 degrees C at 1 microM concentration) and telomerase inhibition in
      the nanomolar region ((tel)EC(50) values of 80-318 nM). Furthermore, a direct
      correlation between the FRET and TRAP assays was observed, supporting the use of
      the rapid screening FRET assay for early assessment of potential G4-stabilising
      telomerase inhibitors.

PMID- 15261301
TI  - D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin
      inhibitors.
AB  - Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI
      286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant
      cell lines expressing P-glycoprotein. Amides derived from proline had potency
      comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols
      or its conversion to acidic heterocycles also gave potent analogs. Synthetic
      modifications of the carboxylic acid could be carried out selectively using a
      wide range of synthetic reagents. Proline analog 3 was found to be effective in a
      human xenograft model in athymic mice.

PMID- 15261302
TI  - Methylation analysis of the promoter F of estrogen receptor alpha gene: effects
      on the level of transcription on human osteoblastic cells.
AB  - In this study, the methylation status of the distal promoter F of estrogen
      receptor alfa (ERalpha) gene in human osteoblastic cells was investigated. The
      activity of this promoter is responsible for the ERalpha gene transcription in
      bone tissue. The methylation status of promoter F was here evaluated, for the
      first time, by direct sequencing of bisulfite-treated genomic DNA, at 10 CpG
      specific sites localized in a region of about 800 bp. An heterogeneous
      methylation pattern was observed. The most notable difference was found at four
      particular CpGs, distant from the exon F transcription start site, showing a
      methylation status that correlates with the expression level, being ERalpha mRNA
      transcription reduced in a partially methylated cells but preserved in
      demethylated cells. The other CpG sites, localized around the transcription start
      site, were always demethylated except for MG-63 cells showing the lowest level of
      ERalpha expression. By quantitative RT-PCR analysis we demonstrated that ERalpha
      gene expression was higher in primary osteoblasts than in bone-derived cells (MG
      63 and SaOS-2) and in all cases the ERalpha mRNA is represented by the isoform F.
      The same 10 CpG sites were investigated in non-osseous cell lines and were found
      fully methylated in ERalpha-negative breast cancer cells (MDA-MB-231) and
      completely demethylated in ERalpha-positive breast cancer cells (MCF7). The
      overall results suggest that methylation of the CpG sites inside ERalpha gene
      promoter F here analyzed may contribute to ERalpha transcriptional control,
      directly or indirectly, influencing the tissue specific expression of the gene.

PMID- 15261303
TI  - Steroidogenic factor 1 differentially regulates basal and inducible steroidogenic
      gene expression and steroid synthesis in human adrenocortical H295R cells.
AB  - The significance of steroidogenic factor 1 (SF-1) in adrenal steroidogenesis was
      studied using adrenocortical cell lines transformed with a dominant negative
      mutant of SF-1. Constitutive expression of the mutant did not only impair the
      activity of endogenous SF-1 but also diminish its own expression, suggesting that
      SF-1 was under autoregulation. Inhibition of the endogenous SF-1 activity
      significantly reduced basal and inducible transcription of CYP17, CYP21B and
      CYP11B1, but exhibited little effects on StAR and CYP11A1 expression. Stimulating
      the transformed cells with potassium and cAMP freed CYP11B2 from the mutant
      caused transcriptional inhibition, whereas the transformation abolished induction
      of CYP17 by both stimulants. Consistent with the transcriptional changes of
      steroidogenic genes, basal and inducible synthesis of cortisol and androgens
      drastically declined in the transformed cell lines. The relief of CYP11B2
      repression following the potassium and cAMP stimulation removed the restraint the
      mutant exerted on aldosterone synthesis, and resulted in aldosterone
      overproduction in the stimulated transformed cells. SF-1 also plays a role in
      regulating the adrenocorticotrophic hormone (ACTH) responsiveness of the
      adrenocortical cells. Inhibition of SF-1 activity significantly decreased basal
      expression of ACTH receptor and its induction by potassium and cAMP.

PMID- 15261304
TI  - Comparative evaluation of androgen and progesterone receptor transcription
      selectivity indices of 19-nortestosterone-derived progestins.
AB  - Synthetic 19-nortestosterone-derived progestins show affinity for the androgen
      receptor (AR) and retain varying degrees of androgenic activity. In this study,
      AR- and progesterone receptor (PR)-dependent transcriptional activation induced
      by norethisterone (NET), levonorgestrel (LNG) and gestodene (GSD), and their
      5alpha-reduced derivatives, including limited trypsin digestion of AR in the
      presence of natural and synthetic progestins were investigated. The results
      confirmed the progestogenic activity of the three 19-nortestosterone derivatives,
      which decreases after reduction of the 4-ene-double bound. These compounds were
      able to activate AR-dependent reporter gene expression, LNG and GSD being the
      stronger activators. 5alpha-Reduction of LNG and GSD did not change their
      androgenic transcriptional activity; however, the activation of AR by 5alpha-NET
      was four-fold higher than NET. The highest selectivity transcriptional index, as
      a measure of progestogenicity versus androgenicity, was obtained for NET. The
      5alpha-reduced derivatives had values significantly lower than those of their
      parent compounds. Non-reduced and 5alpha-reduced 19-nortestosterone progestins
      induced virtually identical proteolysis fragmentation patterns of the AR to those
      observed with DHT.

PMID- 15261305
TI  - Association of increased estrogen receptor beta2 expression with parity-induced
      alterations in the rat mammary gland.
AB  - In this study, we investigated the cellular and molecular events involved in
      parity-related alterations in mammary gland (MG) proliferation and
      differentiation. Rat MGs were removed on day 9 of either first (nulliparous),
      second (primiparous) or third (multiparous) pregnancy. Expression of steroid
      hormone receptors along with cellular biomarkers of proliferation and
      differentiation were quantified in all MG tissue compartments by
      immunohistochemistry. Wnt-4 (a Wingless-like morphogenic gene involved in MG
      development), ERbeta and ERbeta2 mRNA were evaluated by RT-PCR analysis. Serum
      levels of mammotrophic hormones were measured. In comparison to nulliparous and
      primiparous rats, multiparous animals exhibited decreased luminal cell
      proliferation and PR levels, whereas alpha-lactalbumin, ERalpha, ERbeta and
      ERbeta2 expression were increased. In myoepithelial cells, while parity induced a
      decrease in proliferative activity, subsequent pregnancies and lactations lead to
      an increased state of differentiation. Our results showed that at least two
      periods of pregnancy and lactation were necessary to modify the studied
      parameters. The lower proliferative activity and higher differentiation state of
      the multiparous MG are associated with both a decreased PR expression and
      increased ERalpha and ERbeta expression. Since ERbeta and/or ERbeta2 isoform
      expression was related to parity history, results suggest that the decreased
      proliferative activity and PR expression observed in the MG of multiparous
      animals may be associated with overexpression of ERbeta and/or the ERbeta2
      isoform, thereby antagonizing the proliferative effects associated with ERalpha.

PMID- 15261306
TI  - A mammalian steroid action inhibitor spironolactone retards plant growth by
      inhibition of brassinosteroid action and induces light-induced gene expression in
      the dark.
AB  - We screened steroid derivatives and found that spironolactone, an inhibitor of
      both 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and aldosterone receptor,
      is an inhibitor of phytohormone brassinosteroid (BR) action in plants. Under both
      dark and light growing conditions, spironolactone induced morphological changes
      in Arabidopsis, characteristic of brassinosteroid-deficient mutants.
      Spironolactone-treated plants were also nearly restored to the wild-type
      phenotype by treatment with additional BRs. In the spironolactone-treated
      Arabidopsis, the CPD gene in the BR biosynthesis pathway was up-regulated,
      probably due to feedback regulation caused by BR-deficiency. Spironolactone
      treated tobacco plants grown in the dark showed expression of light-regulated
      genes as was observed in the deficient mutant. These data suggest that
      spironolactone inhibits brassinosteroid action probably due to the blockage of
      biosynthesis and exerts its activity against plants. Thus, spironolactone, in
      conjunction with brassinosteroid-deficient mutants, can be used to clarify the
      function of BRs in plants and characterize mutants. The spironolactone action
      site was also investigated by feeding BR biosynthesis intermediates to
      Arabidopsis grown in the dark, and the results are discussed.

PMID- 15261307
TI  - Expression of cytochrome P450c17 and other steroid-converting enzymes in the rat
      kidney throughout the life-span.
AB  - We have investigated the metabolism of [14C]-labelled progesterone (P4) and
      dehydroepiandrosterone (DHEA) by kidney tissues of newborn and 7-, 15-, 30-, 60-
      and 365-day-old rats of both sexes. The following enzymes were revealed at all
      ages by radiochemical identification of the corresponding products: 5alpha
      reductase, cytochromes P450c17 and P450c21, 3beta-hydroxysteroid dehydrogenase
      (HSD)/delta5-delta4 isomerase, and 17beta- and 20alpha-HSDs, catalyzing reductive
      reactions. The major P4 metabolites were 5alpha-reduced C21 steroids, whose
      formation was almost completely suppressed by the 5alpha-reductase 4-azasteroid
      inhibitor, PNU 156765. Androstenedione and testosterone were also formed via
      17alpha-hydroxyprogesterone, together with 11-deoxycorticosterone and 20alpha
      dihydroprogesterone. DHEA was mainly converted to androst-5-ene-3beta,17beta
      diol, with smaller amounts of the above androgens. Cytochrome P450c17 mRNA and
      protein were demonstrated by Northern blotting and Western blotting analyses,
      respectively. P450c17 mRNA, assessed by Northern blotting, protein and catalytic
      activity all peaked in the kidney samples at 15 days of life and declined
      thereafter. Cytochrome P450arom was below the level of detection of semi
      quantitative RT-PCR. Since the rat kidney has been previously shown to contain
      cytochrome P450scc as well as androgen and estrogen receptors, it is suggested
      that it is capable of autonomous hormonal steroidogenesis and that renal
      steroids, or nephrosteroids, may act locally, in a paracrine or autocrine
      fashion.

PMID- 15261308
TI  - Regulation of the lipopolysaccharide signal transduction pathway by 17beta
      estradiol in macrophage cells.
AB  - We have previously shown that 17beta-estradiol (E2) prevents the activation of
      brain macrophages, i.e. microglia cells, both in vitro and in vivo. Hormone
      exerts this inhibitory effect by inhibiting pro-inflammatory gene expression. In
      this study we further investigated on the molecular mechanism of E2 action in the
      RAW 264.7 macrophage cell line. We show here that these cells express the alpha
      isoform of the estrogen receptor (ERalpha) and not ERbeta. Similarly to its
      activity in brain macrophages, E2 is able to inhibit the activation program
      induced by lipopolysaccharide (LPS) in RAW 264.7 cells, as shown by the
      inhibitory effect of hormone on the morphological conversion and matrix
      metalloproteinase-9 (MMP-9) expression induced by the endotoxin. In addition, we
      demonstrate that hormone treatment is not associated with a reduction in the
      steady-state expression of Toll-like receptor-4 (TLR-4) and CD14, two components
      of the LPS receptor complex. Our results further confirm the anti-inflammatory
      role of ERalpha in macrophages and propose that the mechanism of hormone action
      on macrophage reactivity involves signaling molecules which are down-stream
      effectors of the LPS membrane receptors.

PMID- 15261309
TI  - In vitro anti-resorptive activity and prevention of ovariectomy-induced
      osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen
      receptor modulator.
AB  - Antiosteoporotic activity of ormeloxifene, a multifunctional SERM, using
      inhibition in parathyroid hormone (PTH) induced resorption of 45Ca from
      prelabeled chick and rat fetal limb bones in chase cultures and modulation of
      certain biochemical markers of bone turnover and bone mineral density (BMD) in
      ovariectomized adult female rats, was investigated. Ormeloxifene concentration
      dependently inhibited PTH-induced resorption of 45Ca from chick fetal femora with
      treated/control (T/C) ratio of 0.71, 0.32 and 0.20 at 50, 100 and 200 microM
      concentration, in comparison to 0.49, 0.53 and 0.95 in case of CDRI-85/287 (a
      pure antiestrogen), tamoxifen and ethynylestradiol (100 microM), respectively.
      Using rat fetal limb bones, ormeloxifene (100 microM) exhibited T/C ratio of
      0.67, in comparison to 1.43 with PTH alone. Heat-killed bones exhibited
      negligible resorption (2.9%; T/C: 0.098) in response to PTH. In adult female
      rats, ormeloxifene (1.25 and 12.5 mg/kg per day) inhibited ovariectomy-induced
      increase in serum total and bone-specific alkaline phosphatase and osteocalcin
      and urine calcium/creatinine ratio to almost intact control level. Ovariectomy
      was accompanied by marked decrease in bone mineral density of isolated femur and
      tibia, being maximum in femur neck (28.3%; P < 0.01) and midshaft (23.7%; P <
      0.01), but only marginal (6.7%; P > 0.05) in region proximal to tibio-fibular
      separation point. Decrease in BMD based on T-/Z-score, too, was >2.5 S.D. than
      mean value of normal young adult/age-matched females. This was prevented by
      ormeloxifene and the effect, though apparently more in females supplemented with
      higher dose of ormeloxifene, was not always significantly different and clear
      dose-response was not evident until BMD data was evaluated on T-/Z-score basis.
      The analysis also demonstrated much higher threshold level of tibia than femur
      and more so for their mid-shafts. Increase in BMD of isolated bones was also
      observed in ormeloxifene-treated intact females, without significantly altering
      biochemical markers of bone turnover or uterine weight. Findings suggest
      potential of ormeloxifene in management of post-menopausal osteoporosis and
      beneficial effect on BMD in women taking this SERM for contraception or any
      hormone-related clinical disorder.

PMID- 15261310
TI  - Extracellular 3beta-hydroxysteroid oxidase of Mycobacterium vaccae VKM Ac-1815D.
AB  - Extracellular 3beta-hydroxysteroid oxidase (SO) has been isolated from cell-free
      cultivation broth at the growth of Mycobacterium vaccae VKM Ac-1815D on glycerol
      mineral medium in the presence of sitosterol. The enzyme is responsible for the
      transformation of 3beta-hydroxy-5-ene- to 3-keto-4-ene-moiety of steroids
      including dehydrogenation of 3beta-hydroxy function followed by delta5-->delta4
      isomerization. 6-Hydroxy-4-sitosten-3-one and 6-hydroxy-4-androsten-3,17-dione
      were revealed among the metabolites at the incubation of the enzyme preparations
      with sitosterol and dehydroepiandrosterone (DHEA), respectively. The enzyme was
      strongly NADH or NADPH dependent. SO has been purified over 300-fold using
      cultivation broth concentration on hollow fibers followed by fractionation by
      ammonium sulphate, column chromatography on DEAE-Toyopearl, hydroxyapatite Bio
      Gel HTP and double gel-filtration on Bio-Gel A 0.5 M. SDS-electrophoresis gave a
      molecular mass estimate of 62 +/- 4 kDa. The purified SO obeyed Michaelis-Menten
      kinetics, double reciprocal plots kinetics revealed Km value towards DHEA 5 x 10(
      4) M. Along with SO activity, 17-hydroxysteroid dehydrogenase (17-OH SDH) and 3
      ketosteroid-1(2)-dehydrogenase (1(2)-SDH) activities were detected in cell-free
      cultivation broth. The extracellular steroid transforming activities of C-17
      ketosteroid producing mycobacteria were hitherto unreported.

PMID- 15261311
TI  - Novel cytotoxic bufadienolides derived from bufalin by microbial hydroxylation
      and their structure-activity relationships.
AB  - Microbial transformation was used to prepare novel cytotoxic bufadienolides.
      Twelve products (3-14) were obtained from bufalin (1) by the fungus Mucor
      spinosus. Their structures were elucidated by high-resolution mass spectroscopy
      (HR-MS) and extensive NMR techniques, including 1H NMR, 13C NMR, DEPT, 1H-1H
      correlation spectroscopy (COSY), two dimensional nuclear Overhauser effect
      correlation spectroscopy (NOESY), heteronuclear multiple quantum coherence
      (HMQC), and heteronuclear multiple bond coherence (HMBC). Compounds 3, 4, 9 and
      11-14 are new mono- or dihydroxylated derivatives of bufalin with novel
      oxyfunctionalities at C-1beta, C-7beta, C-11beta, C-12beta and C-16alpha
      positions. The in vitro cytotoxic activities against human cancer cell lines of 3
      14, together with 16 biotransformed products derived from cinobufagin (15-30)
      were determined by the MTT method, and their structure-activity relationships
      (SAR) were discussed.

PMID- 15261312
TI  - Remifentanil used to supplement propofol does not improve quality of sedation
      during spontaneous respiration.
AB  - STUDY OBJECTIVE: To evaluate whether the use of remifentanil to supplement
      propofol during spontaneous respiration confers any benefits in terms of quality
      of sedation and recovery, or in terms of reduction in propofol requirements.
      DESIGN: Prospective, randomized, double-blind study. SETTING: University
      hospital. PATIENTS: 50 ambulatory adult ASA physical status I and II patients
      scheduled for total colonoscopy. INTERVENTIONS: Patients were randomized to
      receive either propofol alone or propofol plus remifentanil 0.1 microg/kg/min,
      while independently maintaining spontaneous respiration. MEASUREMENTS:
      Cardiovascular and respiratory variables were measured before induction and at 1
      minute intervals thereafter. Recovery from anesthesia was assessed using simple
      verbal commands and the Steward Post Recovery Score. Patient satisfaction was
      measured with a visual analog scale. Computer simulation was used to calculate
      the effect-site concentrations of propofol and remifentanil. MAIN RESULTS: The
      depressant effects on blood pressure and respiratory function were significantly
      higher when propofol and remifentanil were combined. Although the addition of
      remifentanil resulted in a decrease of propofol usage, recovery of anesthesia was
      faster and patient satisfaction was higher when using propofol alone.
      CONCLUSIONS: The addition of remifentanil to propofol during spontaneous
      ventilation offered no benefits compared with the use of propofol alone.

PMID- 15261313
TI  - Acute respiratory distress syndrome of the contralateral lung after reexpansion
      pulmonary edema of a collapsed lung.
AB  - STUDY OBJECTIVE: To report that leukocyte-mediated acute injury may develop in a
      nonhypoxic lung after hypoxia-reoxygenation injury of the hypoxic lung and in
      other systemic organs in patients with reexpansion pulmonary edema. DESIGN: Case
      report analysis with examination of the literature. SETTING: Intensive care unit
      of a university hospital. PATIENTS: Three patients who developed leukocyte
      mediated acute lung injury in the contralateral lung and systemic organ injury
      after ipsilateral reexpansion pulmonary edema of a collapsed lung. MEASUREMENTS:
      To rule out the possibility that the acute lung injury in the contralateral lung
      was an extension of the hypoxia-reoxygenation injury, we analyzed changes in
      leukocyte and platelet count in the peripheral blood in relation to the
      development of pulmonary edema in each lung. Changes in liver enzymes were also
      analyzed to detect hepatic dysfunction as evidence of systemic organ injury. MAIN
      RESULTS: Both leukocyte and platelet counts decreased when reexpansion pulmonary
      edema developed, and decreased further when acute lung injury developed in the
      contralateral lung (F = 8.42, p = 0.037 for leukocytes, and F = 17.66, p = 0.01
      for platelets). Significant hepatic dysfunction developed, as evidenced by
      increases in both serum bilirubin (p = 0.001) and lactic dehydrogenase,
      indicating the presence of systemic organ injury. CONCLUSIONS: The hypoxia
      reoxygenation injury of one lung can induce acute lung injury in the other lung
      and systemic organ injury.

PMID- 15261314
TI  - Increased success rate with infraclavicular brachial plexus block using a dual
      injection technique.
AB  - STUDY OBJECTIVE: To test the hypothesis that dual injection of the local
      anesthetic in coracoid infraclavicular brachial plexus block might enhance both
      sensory and motor block for anesthesia of the upper limb when compared with a
      single-injection technique. DESIGN: Comparative, prospective, randomized,
      investigator-blinded study. SETTING: University-affiliated hospital. PATIENTS: 60
      patients scheduled for surgery of the hand, forearm, or elbow. INTERVENTIONS:
      Patients were randomly assigned to receive either a coracoid infraclavicular
      block guided by nerve stimulator with a single injection technique (Group 1) or a
      dual-injection technique (Group 2). Injection of 40 mL 1.5% mepivacaine was made
      after eliciting one evoked motor response in the upper limb with a nerve
      stimulator for coracoid infraclavicular block in Group 1 and injection of two
      separate doses of 20 mL 1.5% mepivacaine after elicitation of two motor responses
      in Group 2. MEASUREMENTS: Assessment of sensory and motor block in the upper limb
      5 and 20 minutes after the end of the injection of the local anesthetic. The time
      needed to elicit the second response and to inject the second dose of local
      anesthetic was also recorded. MAIN RESULTS: Significantly higher rates of sensory
      block to pinprick on the distributions of axillary, musculocutaneous, radial,
      ulnar, and medial cutaneous of the forearm nerves were found in Group 2 at 20
      minutes. Significantly higher rates of motor block for arm, wrist, and hand
      movements were found in Group 2 at 20 minutes. CONCLUSIONS: Dual injection of
      local anesthetic guided by nerve stimulator increases the efficacy of coracoid
      block when compared with a single injection of the same dose of local anesthetic.

PMID- 15261315
TI  - Utility of letters sent to patients after difficult airway management.
AB  - STUDY OBJECTIVE: To determine whether postoperative "difficult airway" letters,
      which inform a patient that he has a difficult airway, are an effective way to
      communicate with patients and future caregivers. DESIGN: Patient telephone
      survey. SETTING: Tertiary referral and postgraduate teaching hospital. PATIENTS:
      113 (of a total of 142) patients who were mailed a postoperative "difficult
      airway" letter during the time period 2000-2002, and who agreed to participate in
      the survey. INTERVENTIONS AND MEASUREMENTS: The patients who participated in the
      study were asked a series of questions regarding their difficult airway history,
      including whether or not their primary care provider was aware of their
      condition, whether or not the patient had obtained a MedicAlert bracelet or
      necklace as recommended, whether or not they had undergone subsequent surgery,
      and if so had they conveyed their difficult airway history to their surgeon or
      anesthesiologist. MAIN RESULTS: Of the 142 patients who were sent letters, 113
      agreed to participate. Of those who did not, two patients who were contacted
      refused to participate. Twenty-three patients could not be contacted following
      several attempts, and four patients had died. Twenty-eight patients (20%) stated
      they could not remember receiving a letter. Forty-six (41%) stated that they had
      informed their primary care provider about their difficult airway. Twenty-two of
      24 patients (92%) who had undergone subsequent surgery indicated they had
      informed their anesthesiologist about their airway. Twenty-six patients (23%) had
      registered with the MedicAlert Foundation. As a result of the survey, 44 patients
      requested more information about their airway and MedicAlert. CONCLUSIONS: The
      majority of patients who were sent a "difficult airway" letter did not obtain a
      MedicAlert bracelet, although frequently recommended. However, most of the
      patients who subsequently had surgery informed their anesthesiologist or surgeon
      of their airway history. "Difficult airway" letters may have significant utility
      even if patients do not obtain identifying jewelry.

PMID- 15261316
TI  - Effect of intraoperative magnesium infusion on perioperative analgesia in open
      cholecystectomy.
AB  - STUDY OBJECTIVE: To study the role of magnesium sulphate (MgSO4) on analgesic
      requirement, pain, discomfort, and sleep during perioperative period. DESIGN:
      prospective, double-blinded, randomized study. SETTINGS: Operating room and
      recovery ward at a university teaching hospital. PATIENTS: 50 ASA physical status
      I and II patients scheduled for elective open cholecystectomy with general
      anesthesia. INTERVENTIONS: patients were randomly allocated to receive MgSO4 or
      saline intravenously (i.v.). Patients in the magnesium group received 50% MgSO4
      (50 mg kg(-1)) in 100 mL saline and those in the control group received an equal
      volume of saline i.v. during the preoperative period followed by 50 mL hr(-1)
      infusion of either MgSO4 (15 mg kg(-1) hr(-1)) or saline until the end of
      surgery. MEASUREMENTS AND MAIN RESULTS: Morphine requirement, pain during rest
      and on coughing, discomfort, and insomnia were assessed during the postoperative
      period for 24 hours. Intravenous morphine 40 microg kg(-1) increments were given
      to all patients in the postoperative period for analgesia. Patients in the
      magnesium and control groups had similar morphine requirement during the first 24
      hours postoperatively (p = 0.07). Patients in the magnesium group experienced
      less discomfort during the first hour after the operation. They also had better
      sleep quality during the first postoperative night than did the control group
      patients (p < 0.05). The frequency of side effects was similar in the two groups.
      CONCLUSION: Administration of intraoperative MgSO4 as an adjuvant analgesic in
      patients undergoing open cholecystectomy resulted in better pain relief and
      comfort in the first postoperative hour, but it did not significantly decrease
      the postoperative morphine requirement. Magnesium sulphate resulted in better
      sleep quality during the postoperative period, without any significant adverse
      effects. The role of MgSO4 as an adjuvant analgesic in open cholecystectomy needs
      to be studied further.

PMID- 15261317
TI  - Differential pressor response to intravenous ephedrine during recovery from
      deliberate hypotension.
AB  - STUDY OBJECTIVE: To determine whether nitroglycerin or trimethaphan alters
      pressor response to intravenous (i.v.) ephedrine. DESIGN: Prospective, randomized
      study. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA
      physical status I female patients scheduled for mastectomy. INTERVENTIONS:
      Patients were assigned to one of six groups (n = 10 in each). Group 1:
      nitroglycerin + normal saline (NS) i.v., Group 2: nitroglycerin + ephedrine 0.1
      mg/kg i.v., Group 3: nitroglycerin + ephedrine 0.15 mg/kg i.v., Group 4:
      trimethaphan + NS i.v., Group 5: trimethaphan + ephedrine 0.1 mg/kg i.v., and
      Group 6: trimethaphan + ephedrine 0.15 mg/kg i.v. MEASUREMENTS: Hemodynamic
      responses to ephedrine following withdrawal of vasodilators were observed for 15
      minutes. MAIN RESULTS: Ephedrine increased heart rate and mean blood pressure.
      After ephedrine 0.1 mg/kg i.v., the maximum pressor response in the trimethaphan
      group was approximately twofold that of the nitroglycerin group (p = 0.038).
      CONCLUSIONS: Ephedrine restored BP more easily in those patients who had received
      trimethaphan compared with those who had received nitroglycerin for deliberate
      hypotension.

PMID- 15261318
TI  - Rapid sevoflurane induction compared with thiopental.
AB  - STUDY OBJECTIVES: To examine whether the speed of induction of anesthesia with
      sevoflurane/nitrous oxide (N2O) utilizing a 10-second vital capacity rapid
      inhalation induction (VCRII) followed by tidal breathing was similar or faster
      than cautious intravenous (i.v.V) thiopental induction with inhaled N2O. DESIGN:
      Prospective, randomized, double-blinded study. SETTING: Veterans Affairs Medical
      Center. PATIENTS: 50 male ASA physical status I, II, and III patients scheduled
      for general anesthesia. INTERVENTIONS: Patients were randomized to receive either
      8% sevoflurane or i.v. thiopental. Patients were allocated to one of two groups
      of 25 patients each. In both groups, the breathing circuit was initially primed
      for 5 minutes with (4 L/min) and O2 (2 L/min), while the Y-piece was occluded. In
      the sevoflurane group, the circuit was additionally primed with 8% sevoflurane.
      Patients were trained to perform a vital capacity breath. After maximal
      exhalation, the occluding plug was rapidly removed from the Y-piece and connected
      to the facemask. The patient then inspired to vital capacity, held his breath for
      10 seconds, and then was allowed to breathe normally. At the end of the 10-second
      breathhold, and as the patient started normal breathing, either thiopental
      (thiopental group) or normal saline (sevoflurane group) was injected at a rate of
      4 mL every 10 seconds. MEASUREMENTS: A study-blinded observer recorded the time
      to induction, as defined by the time to loss of eyelash reflex, and noted the
      occurrence of side effects. MAIN RESULTS: The speed of induction was the same for
      both groups (p > 0.05). An average of eight breaths was required before loss of
      eyelash reflex. Side effects occurred in 36% of the patients in the thiopental
      group, and 32% in the sevoflurane group (p > 0.05); these were minor and did not
      affect induction. CONCLUSION: Sevoflurane/N2O VCRII as used in this investigation
      is an effective inhalation technique; it resulted in an induction time similar to
      that of slow i.v. thiopental with inhaled N2O.

PMID- 15261319
TI  - Nausea and vomiting after outpatient ACL reconstruction with regional anesthesia:
      are lumbar plexus blocks a risk factor?
AB  - STUDY OBJECTIVE: To track the incidence of in-hospital postoperative nausea and
      vomiting (PONV) requiring postoperative parenteral nursing interventions after
      outpatient reconstruction of the anterior cruciate ligament (ACL) with one of two
      types of regional anesthesia to determine the extent to which various anesthetic
      techniques, preemptive antiemetics, and other factors were associated with the
      lowest probability of PONV. DESIGN: Retrospective chart (database) review of all
      ACL procedures at the University of Pittsburgh Medical Center from August 1997
      through June 1999. SETTING: University medical center. MEASUREMENTS: We reviewed
      our institutional database of 347 consecutive patients undergoing ACL
      reconstruction with either spinal with femoral nerve block (SPI-FNB) or lumbar
      plexus and sciatic nerve block (LUM-SCI). Recorded variables and outcomes
      included gender, history of PONV, intravenous (i.v.) fentanyl before and during
      surgery, preemptive antiemetics given, and parenteral nursing interventions for
      PONV performed. Chi-square tests and logistic regression were used to determine
      factors associated with PONV. MAIN RESULTS: For SPI-FNB, PONV incidence was 13%
      (26/208), but it was higher for LUM-SCI [25%, 34/139, p = 0.002; odds ratio (OR)
      = 2.2]. Regression modeling demonstrated that women (OR = 2.8, p = 0.003) and LUM
      SCI patients (OR = 3.0, p = 0.005) were at greater risk for PONV. The combination
      of dexamethasone (4 to 10 mg i.v.) and perphenazine (1.2 to 2.0 mg i.v.) was
      associated with less PONV (OR = 0.3, p = 0.005). Type of local anesthetic used
      for lumbar plexus block was not associated with PONV incidence. CONCLUSIONS: For
      ACL reconstruction with regional anesthesia, use of LUM-SCI was associated with a
      higher rate of PONV, whereas combination antiemetic prophylaxis with perphenazine
      and dexamethasone was associated with less PONV.

PMID- 15261320
TI  - Increased propofol requirement during succeeding administrations for
      electroconvulsive therapy.
AB  - STUDY OBJECTIVE: To study patients' requirement for propofol dosages during the
      course of repeated deep sedation for electroconvulsive therapy (ECT). DESIGN:
      Prospective study. SETTING: Outpatient psychiatric clinic in a tertiary-care,
      university-affiliated, 1100-bed metropolitan hospital. PATIENTS: 30 patients
      undergoing 5-day successive ECT for depression over a 1-month period.
      INTERVENTIONS: Propofol and subsequently succinylcholine were injected
      intravenously (i.v.) to obtain deep sedation and relaxation followed by a 60 +/-
      5 (SD) joules-ECT. MEASUREMENTS: The dosage that was required to deeply sedate
      the patients, the duration of the ECT, and interval of time to full wakefulness
      and coherent response were measured. MAIN RESULTS: 13 of 30 patients 1) required
      >100% increase in the dose of propofol to achieve the same pharmacological
      prerequisite sedative endpoint, starting from their third treatment onward; 2)
      there was a 35% abbreviated duration of the convulsive activity; and 3) there was
      a 21% shortened interval of time to full wakefulness and coherent communication,
      starting at the fourth propofol injection. CONCLUSIONS: Repeated injections of
      propofol in patients undergoing ECT under deep sedation can induce a tolerance
      like reaction to the drug.

PMID- 15261321
TI  - Small change in capnography led to the detection of an intravascular thrombus.
AB  - This report highlights the importance of accurate interpretation of even small
      intraoperative capnography changes. In this case, an otherwise unexplained sudden
      small decrease in end-expiratory carbon dioxide tension (P(ET)CO2) led to the
      detection of a deep venous thrombus. During the surgery of a 34-year-old woman
      with a known carcinoma of the corpus uteri, who was scheduled for paraaortal
      lymphadenectomy, a sudden decrease in carbon dioxide tension occurred. In careful
      exploration of the surgical field to rule out a thromboembolic event, the
      surgeons noticed an induration of the right iliac vein. A consulting vascular
      surgeon exposed a right-sided, irregular, double-lumen, common iliac vein with a
      thrombus the tip of which floated in the inferior vena cava. Following complete
      thrombectomy, the procedure was accomplished without further adverse events.

PMID- 15261322
TI  - Reexpansion pulmonary edema after resolution of tension pneumothorax in the
      contralateral lung of a previously lung injured patient.
AB  - We present the case of a 19-year-old woman who developed sudden severe left-sided
      tension pneumothorax in the recovery room after undergoing a 6-hour open
      reduction and internal fixation of an anterior and posterior pelvic fracture
      sustained in a motor vehicle accident 4 days prior to surgery. Additional
      preoperative injuries included a right-sided hemopneumothorax, right lung
      contusion, and liver laceration. The left lung was rapidly reexpanded using tube
      thoracostomy. The patient subsequently developed ipsilateral pulmonary edema and
      ultimately acute respiratory distress syndrome, which required vigorous treatment
      over the next several days. It is postulated that a variety of intraoperative and
      immediate postoperative maneuvers may have contributed to the development of this
      near fatal complication.

PMID- 15261323
TI  - Hemorrhagic stroke after spinal anesthesia and minor surgery.
AB  - This report describes a case of hemorrhagic stroke that presented as an
      expressive aphasia after routine hernia repair under spinal anesthesia in an
      otherwise generally healthy middle-aged outpatient. Possible roles of preexisting
      migrainous headaches and perioperative ephedrine are discussed, but, as in most
      cases of perioperative stroke, the possibilities are numerous and the cause of
      the stroke difficult to determine.

PMID- 15261324
TI  - Lumbar discogram resulting from lumbar interlaminar epidural injection.
AB  - Lumbar discography is a diagnostic modality to determine whether the
      intervertebral disc is the cause of pain. The injection of radiopaque contrast
      into the nucleus pulposus of the disc can reveal the internal details of the
      disc. We describe a case of inadvertent lumbar discogram resulting from an
      attempted lumbar interlaminar epidural injection at L5-S1 under fluoroscopy. The
      patient did not have a postdural puncture headache or nerve root irritation. The
      potential triangle in the lateral aspect of spinal cord may be the explanation
      for this situation, because this triangle is composed of the exiting nerve root
      laterally, the lateral margin of the dura medially, and the pedicle as its base.
      The L5-S1 disc is located in the center of the triangle. In our case, the Tuohy
      needle was placed possibly in the center of the triangle, too laterally to
      puncture the dura. Hence, the patient did not suffer from postdural puncture
      headache. The needle was probably inferior to the nerve root, and no obvious
      nerve root trauma or irritation occurred. This potential triangle may provide
      alternative access for lumbar discography at the L5-S1 level.

PMID- 15261325
TI  - Ascending tonic-clonic syndrome secondary to intrathecal Omnipaque.
AB  - A 52-year-old man experienced progressive tonic-clonic activity soon after
      undergoing a myelogram accompanied by an intrathecal injection of Omnipaque. The
      activity progressed to seizures, hyperthermia, and acidosis. He was intubated,
      cooled, and treated symptomatically. His creatinine kinase rose to 60,000 IU/L.
      He eventually recovered completely. This distinct set of clinical signs renders
      the syndrome easily recognizable. Although this syndrome superficially resembles
      malignant hyperthermia, the pathophysiology is different. Survival depends on
      prompt recognition and rapid symptomatic treatment. Treatment with dantrolene
      sodium is not necessary.

PMID- 15261326
TI  - Upper airway obstruction caused by a double-cuffed nasal balloon after
      extubation.
AB  - This case report highlights a situation in which a double-cuffed nasal balloon
      tamponade device can cause an upper airway obstruction. An 89-year-old female
      required general anesthesia for an emergent embolization for right-sided
      epistaxis. The patient had no signs of upper airway obstruction when a double
      cuffed nasal tamponade balloon was in place prior to general anesthesia. However,
      upper airway obstruction occurred immediately after extubation and was corrected
      by cuff deflation. The mechanisms of upper airway obstruction as a result of cuff
      dysfunction and management are discussed.

PMID- 15261327
TI  - Anesthetic considerations of the herbal, kava.
AB  - The herbal remedy, kava, is reviewed, with special focus on the anesthetic
      management of the perioperative patient. Consumption of kava has potential
      cardiovascular consequences that could manifest in the perioperative period. Kava
      may act through inhibition of sodium and calcium channels to cause direct
      decreases in systemic vascular resistance and blood pressure. Kava inhibits
      cyclooxygenase to potentially cause a decrease in renal blood flow and to
      interfere with platelet aggregation. Kava may also cause adverse neurologic
      effects because of benzodiazepine and antidepressant activities on noradrenergic
      and/or serotoninergic pathways that may potentiate benzodiazepine and induction
      anesthetic potency and cause excessive perioperative sedation. Patients often do
      not disclose their use of herbal substances, and drug interaction can occur
      without being suspected as the cause for a change in patient homeostasis. A role
      for patient education about the potential adverse consequences of kava use in the
      perioperative period is suggested.

PMID- 15261328
TI  - The Airway Approach Algorithm: a decision tree for organizing preoperative airway
      information.
AB  - Anticipatory decision-making in airway management requires the integration of
      both history and physical examination findings. Though all airways can be managed
      along some branch of the American Society of Anesthesiologists' (ASA) Difficult
      Airway Algorithm, by predicting specific difficulties and integrating this
      information into an airway approach strategy, emergency branches of the ASA
      algorithm may be avoided. The Airway Approach Algorithm (AAA) consists of five
      clinical questions, with "yes" or "no" answers, to be addressed prior to the
      management of the airway. A positive answer to any question leads the clinician
      to the next, whereas a negative answer directs the operator to a root point of
      the ASA algorithm. The AAA is introduced with the anticipation that trainees in
      Anesthesiology, as well as others, will find it helpful in organizing
      preoperative information concerning the airway.

PMID- 15261329
TI  - In vitro autoradiographic localization of calcitonin and amylin binding sites in
      monkey brain.
AB  - Calcitonin (CT) and amylin are related peptides with potent central actions,
      including suppression of appetite and gastric acid secretion. Little is known
      about the distribution and binding characteristics of amylin receptors in species
      other than rat; therefore, in this study, by using in vitro autoradiography, we
      have mapped the distribution of 125I-rat amylin binding sites in the monkey brain
      and compared this distribution to that of binding sites for 125I-salmon CT (125I
      sCT). Highest densities of 125I-amylin binding were in the hypothalamus,
      including the arcuate nucleus and parts of the ventromedial hypothalamic nuclei,
      and the solitary nucleus. Rostrally, moderate to high density binding was present
      in parts of the preoptic area, bed nucleus of the stria terminalis, amygdala and
      accumbens nucleus (Acb). Caudally, binding of amylin was more restricted, with
      moderate to high density binding present only in dorsal raphe, and area postrema.
      The primary visual cortex displayed strong and periodic CT binding in layer 4.
      The subcortical pattern of distribution of amylin and CT receptors in the monkey
      was similar to that seen previously in the rat, although the relative densities
      of binding to different brain structures were not always conserved. As with rat,
      monkey amylin receptors were a subset of the sites labeled with 125I-sCT.
      Analysis of receptor specificity indicated a greater relative potency of CT
      peptides in competing for 125I-amylin binding in monkey, when compared to rat,
      while, there was a decrease in the relative potency of CT gene-related peptides,
      potentially due to differences the level of receptor activity modifying proteins
      (RAMPs) in monkey versus rat brain. Amylin receptors in primates are likely to
      perform a similar role to those in rats; however, the interaction of the
      receptors with related peptides may differ.

PMID- 15261330
TI  - Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects on
      cytochrome oxidase activity in skeletal muscle and brain.
AB  - In order to furnish a combined model of relevance to human inclusion-body
      myopathy and Alzheimer's disease, transgenic mice expressing human betaAPP-C99 in
      skeletal muscle and brain under the control of the cytomegalovirus/beta-actin
      promoter were produced (Tg13592). These transgenic mice develop Abeta deposits in
      muscles but not in brain. Cell metabolic activity was analyzed in brain regions
      and muscle by cytochrome oxidase (CO) histochemistry, the terminal enzyme of the
      electron transport chain. By comparison to age-matched controls of the C57BL/6
      strain, CO activity was selectively increased in dark skeletal muscle fibers of
      Tg13592 mice. In addition, only increases in CO activity were obtained in those
      brain regions where a significant difference appeared. The CO activity of Tg13592
      mice was elevated in several thalamic nuclei, including laterodorsal,
      ventromedial, and midline as well as submedial, intralaminar, and reticular. In
      contrast, the groups did not differ in most cortical regions, except for
      prefrontal, secondary motor, and auditory cortices, and in most brainstem
      regions, except for cerebellar (fastigial and interpositus) nuclei and related
      areas (red and lateral vestibular nuclei). No variation in cell density and
      surface area appeared in conjunction with these enzymatic alterations. The
      overproduction of betaAPP-C99 fragments in brain without (amyloidosis did not
      appear to affect the metabolic activity of structures particularly vulnerable in
      Alzheimer's disease.

PMID- 15261331
TI  - Detection of nitric oxide synthase (NOS) immunoreactive neurons in the human
      septal area: a matter of method?
AB  - There is a remarkable discrepancy between biochemical and cell morphological
      findings with regard to the presence of NADPH diaphorase/neuronal nitric oxide
      synthase (NOS) in the primate septal area. Whereas considerable concentrations of
      neuronal nitric oxide synthase and high enzyme activities have been measured in
      postmortem human septal nuclei, histochemical studies were either unable to
      detect any nitric oxide synthase immunoreactivity in primate septal neurons, or
      found only a very few nitrergic neurons in this region. This study aimed to
      investigate the possible presence of nitrergic neurons in human the septal region
      in greater detail. After having studied a total of 16 postmortem human brains we
      conclude that the immunohistochemical demonstration of nitric oxide synthase in
      human septal neurons is largely dependent on the mode of tissue handling: in
      brain specimens which were fixed en-bloc with paraffin and embedded in paraplast,
      nitric oxide synthase immunoreactivity is barely detectable, whereas a satisfying
      immunostaining is obtained on free-floating frozen sections after an immersion
      fixation with 4% paraformaldehyde and 0.5% glutaraldehyde, followed by sucrose
      protection of the specimens. We show herein that there are indeed nitric oxide
      synthase-containing neurons in the human septum, thus supporting results from
      previous biochemical studies.

PMID- 15261332
TI  - Substance P (NK1) and somatostatin (sst2A) receptor immunoreactivity in NTS
      projecting rat dorsal horn neurones activated by nociceptive afferent input.
AB  - Spinal neurones that receive inputs from primary afferent fibres and have axons
      projecting supraspinally to the medulla oblongata may represent a pathway through
      which nociceptive and non-nociceptive peripheral stimuli are able to modulate
      cardiorespiratory reflexes. Expression of the neurokinin-1 (NK1) receptor is
      believed to be an indicator of lamina I cells that receive nociceptive inputs
      from substance P releasing afferents, and similarly, sst2A receptor expression
      may be a marker for neurones receiving somatostatinergic inputs. In this study,
      immunoreactivity for these two receptors was investigated in rat spinal neurones
      retrogradely labelled by injections of cholera toxin B or Fluorogold into the
      nucleus of the solitary tract (NTS). In addition, nociceptive activation of these
      labelled cells was studied by immunodetection of Fos protein in response to
      cutaneous and visceral noxious chemical stimuli. NK1 and sst2A receptors in
      lamina I were localised to mainly separate populations of retrogradely labelled
      cells with fusiform, flattened and pyramidal morphologies. Examples of projection
      neurones expressing both receptors were, however observed. With visceral
      stimulation, many retrogradely labelled cells expressing c-fos were
      immunoreactive for the NK1 receptor, and a smaller population was sst2A positive.
      In contrast, with cutaneous stimulation, only NK1 positive retrogradely labelled
      cells showed c-fos expression. These data provide evidence that lamina I neurones
      receiving noxious cutaneous and visceral stimuli via NK1 receptor activation
      project to NTS and so may be involved in coordinating nociceptive and
      cardiorespiratory responses. Moreover, a subpopulation of projection neurones
      that respond to visceral stimuli may receive somatostatinergic inputs of
      peripheral, local or supraspinal origins.

PMID- 15261333
TI  - Identification of neurons with acetylcholinesterase and NADPH-diaphorase
      activities in the centrifugal visual system of the chick.
AB  - The isthmo-optic nuclei (ION) and ectopic neurons, which constitute the
      centrifugal visual system (CVS), are thought to be cholinoceptive and nitrergic.
      However, it is not clear which neurons express these markers, namely the ones
      that project to the retina rather than in neurons that only participate in a
      local circuit. Therefore, to characterize the neurochemical patterns of the
      centrifugal visual system in the post-hatched chick, retinopetal cells of the
      isthmo-optic nuclei and the ectopic region were identified via immunolabeling for
      cholera toxin, a neuronal tracer, which has been injected in the ocular globe.
      Then, double labeled with acetylcholinesterase histochemistry to reveal
      cholinergic synapses, or NADPH-diaphorase histochemistry as a nitrergic marker.
      Briefly, acetylcholinesterase activity was present mainly in cholera toxin
      labeled cell bodies of the isthmo-optic nucleus and the ectopic region indicating
      that retinal projecting neurons of centrifugal visual system comprise a
      cholinoceptive pathway. On the other hand, NADPH-diaphorase histochemistry was
      present in the neuropile and sparse cell bodies inside of the isthmo-optic
      nucleus and in ectopic neurons which were not cholera toxin positive suggesting
      their role in an intrinsic circuit of the centrifugal visual system. These data
      support the idea that these two neurochemical systems are present in distinct
      neuronal populations in the centrifugal visual system.

PMID- 15261334
TI  - Distribution of ACTH immunoreactivity in the diencephalon and the brainstem of
      the dog.
AB  - The present work describes for the first time the anatomical distribution of
      adrenocorticotropic hormone (ACTH) in the diencephalon and the brainstem of the
      dog by means of the indirect immunoperoxidase technique. The distribution found
      in this species agrees well with the pattern found in other mammals and
      particularly confirms much of the findings reported in the cat. An exception to
      that concordance is the presence of ACTH perikarya in the nucleus of the solitary
      tract of the dog, a population that has been described in the rat but not in the
      cat, and in the ventral mesencephalon. This last population spread across the
      ventral tegmental area from the raphe to the cerebral peduncle and appeared to be
      a specific feature of the canine brain. On the other hand, we can not see ACTH
      fibers in the substantia nigra of the dog which could be a characteristic of the
      domestic carnivores, opposite to rodents, since these fibers appeared to be also
      lacking in the cat. Nevertheless, the widespread distribution of ACTH fibers in
      the brain of the dog included many other nuclei containing monoaminergic neurons
      which supported a possible role for ACTH in the regulation of these
      neurotransmitter systems.

PMID- 15261335
TI  - Mechanisms of apoptosis.
AB  - The understanding of the apoptotic program has grown exponentially over the past
      decade. Numerous human diseases have been directly linked to genetic defects in
      the apoptotic pathways, including cancer, neurodegenerative disorders, and
      autoimmune diseases. Caspases initiate and amplify various death signals,
      allowing for selective and ordered cellular demolition. The fine balance between
      pro- and antiapoptotic Bcl-2 family members regulates the cell fate in response
      to many (but not all) stress or signaling pathways. Recent discoveries highlight
      the complex integration of signals from various organelles that determine cell
      fate and the multiple functions of central players in the apoptotic process. It
      is likely that the knowledge obtained in a relatively time will translate into
      better diagnostics and therapies to enhance or retard cell death in the
      appropriate clinical circumstances.

PMID- 15261336
TI  - Altered structure of autoantigens during apoptosis.
AB  - The clustering and concentration of autoantigens at the surface of apoptotic
      cells, in combination with the striking tolerance-inducing function of apoptotic
      cells, have focused attention on abnormalities in apoptotic cell execution and
      clearance as potential susceptibility and initiating factors in systemic
      autoimmunity. Structural changes that occur during cell death may influence the
      immunogenicity of self antigens. This article discusses the modifications that
      autoantigens undergo during cell death, identifies certain proimmune forms of
      apoptotic death in which autoantigen structure is frequently modified, and
      reviews the mechanisms through which such structural changes might lead to
      initiation of an autoimmune response.

PMID- 15261337
TI  - Genetic models for the clearance of apoptotic cells.
AB  - The immunogenic potential of nuclear antigens exposed during apoptosis, together
      with considerable animal data suggesting that impaired apoptotic clearance can
      result in systemic lupus erythematosus (SLE)-like autoimmunity, has lent support
      to the idea that self-immunization with apoptotic debris is a key driving
      mechanism in lupus. The multiple roles of complement receptors, diverse scavenger
      receptors, and intermediate proteins that bind to and opsonize apoptotic cells
      indicate a complex web of interactions leading to the clearance of apoptotic
      debris. Disturbances in parts of this system may lead to lupus or to lupus
      exacerbations. Therapy directed toward augmenting clearance and decreasing
      concomitant inflammation may lead to improved management of SLE.

PMID- 15261338
TI  - The role of death-associated molecular patterns in the pathogenesis of systemic
      lupus erythematosus.
AB  - This article describes apoptotic cell clearance mechanisms and discusses altered
      mechanisms for clearance of dying material, which represents a central pathogenic
      process in the development and acceleration of systemic lupus erythematosus. The
      article also explores ways to use this perspective for a potential direction for
      future treatments.

PMID- 15261339
TI  - Apoptosis and systemic lupus erythematosus.
AB  - Reduced clearance of dying cells by macrophages or increased apoptosis provokes
      accumulation of cellular fragments in various tissues. This process seems to
      induce the uptake of autoantigens from apoptotic nuclei or chromatin by dendritic
      cells (DCs). Then, the DCs present altered self-epitopes to naive T cells. Thus,
      autoreactive T cells are activated accidentally and may now provide T-cell help
      for B cells that present peptides processed from secondary necrotic/late
      apoptotic prey. Impaired phagocytic removal of early apoptotic cells may cause
      accumulation of secondary necrotic cells and debris in the germinal centers of
      secondary lymph organs. The latter bind complement and can, therefore, be trapped
      on the surfaces of follicular DCs (FDCs). B cells may get in contact with
      intracellular autoantigens that had been released during late stages of apoptotic
      cell death and are immobilized by FDCs. Consecutively, B cells that had, for
      example, gained specificity for nuclear auto-antigens during random somatic
      mutations can receive a short-term survival signal. After migration into the
      mantle zone, these autoreactive B cells may finally be activated by autoreactive
      CD4+ T helper cells. B cells then differentiate into memory or plasma cells. The
      plasma cells produce those pathogenic nuclear autoantibodies. Many defects are
      known with respect to the clearance of apoptotic cells and cell material,
      especially that of nuclear origin. Reflecting on the plethora of defects of
      clearance of apoptotic material already demonstrated in systemic lupus
      erythematosus, it is reasonable to argue that, for many patients, failure of
      clearance is at the heart of their disease.

PMID- 15261340
TI  - Nucleosomes in the pathogenesis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is characterized by the development of a large
      array of autoantibodies that primarily are directed against the whole chromatin
      (antinucleosome) and its individual components, dsDNA and histones. Apoptotic
      defects and impaired removal of apoptotic cells could contribute to an overload
      of autoantigens (and in particular of nucleosomes) in circulation or in target
      tissues that could become available to initiate an autoimmune response. In
      susceptible individuals, this can lead to autoantibody-mediated tissue damage. In
      addition to intrinsic or secondary apoptosis/apoptotic cell removal defects,
      certain apoptotic stimuli (eg, UV, viruses) could lead to posttranscriptional
      modifications that generate autoantigen cryptic fragments for which cells of the
      immune system have not been tolerized. Besides their role as a major immunogen in
      lupus, nucleosomes participate in antibody-mediated renal pathogenicity and act
      as a bridging molecule that recognizes heparin sulfate/collagen V components of
      the glomerular basement membrane. New tools that were developed to detect
      antinucleosome antibodies in the serum of patients (by ELISA) have shown the
      specificity and the high sensitivity of antinucleosome antibody reactivity in
      SLE. In particular, antinucleosome could be a useful marker of patients who have
      SLE and lack anti-dsDNA antibodies, a prognosis marker for imminent relapse, and
      a diagnosis marker of lupus nephritis.

PMID- 15261341
TI  - The stimulation of Toll-like receptors by nuclear antigens: a link between
      apoptosis and autoimmunity.
AB  - As immunologists have long understood, effective responses to foreign antigens
      require adjuvants. It is now apparent that the initiation of autoimmune disease
      is comparably facilitated by adjuvant activity. In the case of antinuclear
      antibodies, it seems that DNA itself can serve as an endogenous adjuvant. Similar
      to many of the microbial adjuvants, mammalian DNA mediates its effect through a
      Toll-like receptor--in this case, TLR9.

PMID- 15261342
TI  - DNA as a marker of cell death in systemic lupus erythematosus.
AB  - DNA circulates in the blood in systemic lupus erythematosus, among other
      conditions, and plays a role in immunopathogenesis in the form of immune
      complexes. As shown in experiments in mice, blood DNA levels rise following
      treatments to induce apoptosis and the administration of cells made apoptotic or
      necrotic in vitro. In mice lacking macrophage function, however, blood levels do
      not rise following administration of dead cells. These results indicate that
      circulating DNA may be a marker of cell death, although its levels likely reflect
      a complex process involving the interactions of macrophages with dead and dying
      cells.

PMID- 15261343
TI  - More to death than dying: apoptosis in the pathogenesis of SSA/Ro-SSB/La
      associated congenital heart block.
AB  - The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and
      perpetuate inflammation and eventuate in scarring of the atrioventricular node
      (the signature lesion of congenital heart block) is not yet defined. In vitro and
      in vivo studies suggest that one pathologic cascade that leads to scarring may be
      initiated by way of apoptosis which results in translocation of SSA/Ro-SSB/La
      antigens and subsequent surface binding by maternal autoantibodies. These
      opsonized cardiocytes are phagocytosed by macrophages,which secrete factors that
      modulate fibroblasts into myofibroblasts,a scarring phenotype. The exaggerated
      apoptosis (amplified physiologic apoptosis or defective clearance) that is
      observed in autopsy slides from fetuses who had congenital heart block may
      provide the pivotal clue to understanding the pathogenicity of the maternal
      autoantibodies.

PMID- 15261344
TI  - Apoptosis in rheumatoid arthritis: friend or foe.
AB  - A better understanding of the mechanisms that contribute to the resistance of
      synovial macrophages and fibroblasts to apoptosis will not only provide better
      insights into the mechanisms contributing to the perpetuation of rheumatoid
      arthritis (RA) but will also help identify targets for the development of novel,
      more effective, and long-lasting therapies for the treatment of patients with RA.
      To avoid toxicity, such as the induction of apoptosis of critical organs, the
      mechanisms by which these molecules are targeted and therapy delivered must be
      carefully selected, using the insights obtained from studies characterizing the
      mechanisms that promote chronic inflammation.

PMID- 15261345
TI  - HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in
      arthritis.
AB  - For the second time in recent history, studies directed at the pathogenesis of
      infectious disease have led to the identification of an endogenous mediator of
      arthritis. HMGB1, a 30-kD nuclear and cytoplasmic protein widely studied as a DNA
      binding protein, is a newly described cytokine and a necessary and sufficient
      mediator of lethal sepsis. HMGB1 is passively released during cell necrosis, but
      not apoptosis; it activates an inflammatory response to necrosis,but not
      apoptosis. Furthermore, HMGB1 can also be actively secreted by stimulated
      macrophages or monocytes in a process that requires acetylation of the molecule,
      enabling a translocation from the nucleus to secretory lysosomes. Recent evidence
      indicates that HMGB1 is a mediator of arthritis because of the following: (1) it
      is produced at the site of joint inflammation, (2) it causes the development of
      arthritis when applied to normal joints, and (3) therapies that inhibit HMGB1
      prevent the progression of collagen-induced arthritis in rodents. Anti-HMGB1 may
      be studied in future clinical trials of diseases of excessive production of
      HMGB1, such as severe sepsis and arthritis.

PMID- 15261346
TI  - Apoptosis in osteoarthritis.
AB  - Many studies have shown that apoptotic cell death occurs at an increased rate in
      osteoarthritic cartilage. Whichever type of cell death takes places in articular
      cartilage, it is important to prevent, because it is detrimental to articular
      cartilage maintenance. Thus, it is important to characterize events going on
      during cellular degeneration in more detail. Overall, physicians have reached a
      reasonable level of understanding of the extent of cell death occurring in the
      disease process, but they are still at an early stage in the understanding of the
      mechanisms underlying this process and the means of intervening in this facet of
      cartilage destruction.

PMID- 15261347
TI  - Apoptosis in glomerulonephritis.
AB  - Apoptosis is of fundamental importance and plays a key role in determining the
      outcome of glomerulonephritis. Under ideal circumstances,apoptosis deletes
      infiltrating leukocytes and excess numbers of resident cells that are surplus to
      requirements, thereby facilitating tissue remodeling and the restoration of
      normal tissue architecture. Apoptosis also has a darker side, however, and may be
      responsible for the deletion of critically important resident glomerular cells,
      resulting in hypocellular scarring and loss of renal function. Recent data
      indicate that glomerular cell apoptosis may be manipulated to improve outcome in
      experimental models of renal inflammation. It is hoped that further research will
      provide novel therapeutic strategies for patients with inflammatory
      glomerulonephritis.

PMID- 15261349
TI  - Predictors of outcome in geriatric patients with urinary tract infections.
AB  - A study was conducted to determine the prognosis of geriatric patients with
      urinary tract infections (UTIs) and identify clinical factors associated with
      adverse outcomes. This retrospective, cohort study identified elderly patients
      (age > or =65 years) presenting to an academic, urban Emergency Department (ED)
      during a 16-week period with UTI, suggested by urinalysis and pertinent symptoms.
      There were 37 demographic and clinical variables analyzed as potential predictors
      of outcome. Morbidity was defined as in-hospital death, Intensive Care Unit (ICU)
      admission, hospital length of stay (LOS) >2 days, or hospital intravenous (i.v.)
      antibiotics >2 days. Factors identified by univariate analysis were combined
      using multiple logistic regression to identify independent predictors of
      morbidity. There were 284 patients who met selection criteria. Thirteen patients
      (4.6%) died during hospitalization and 27 (9.5%) had ICU admission, 139 (48.9%)
      had LOS >2 days, and 75 (26.4%) had i.v. antibiotics >2 days. Multivariate
      analysis identified the following variables as independent predictors of adverse
      outcomes: mental status change, frequent UTIs, other nonurinary infections,
      abnormal temperature, tachycardia, hypotension, elevated BUN, hyperglycemia,
      elevated WBC, and relative neutrophilia. Regression models for adverse outcomes
      had sensitivities from 74.8% to 96.2% and specificities from 31.1% to 69.0%. In
      conclusion, this study defines high rates of morbidity for geriatric patients
      with UTIs and describes predictive variables that may help identify low-risk
      patients. These data may lay the foundation for determining specific guidelines
      for disposition of this high-risk patient population.

PMID- 15261350
TI  - Evaluation of unpredictable critical conditions of patients treated in the
      observation unit of the Emergency Department.
AB  - We evaluated unpredictable critical conditions of patients treated in the
      Emergency Department (ED) observation unit, who were transferred into the
      emergency resuscitation room from January 1 through June 30, 2001. A total of 175
      patients were observed for the following critical conditions: dyspnea (51
      patients; 29.14%), hypotension (28; 16.00%), chest pain (18; 10.29%), dysrhythmia
      (15; 8.57%), hematemesis (15; 8.57%), altered mental status (12; 6.85%), shock
      (10; 5.71%), coma (8; 4.57%), apnea (5; 2.86%), hematochezia (3; 1.72%), seizure
      (3; 1.72%), and others (7; 4.00%). The 27 patients who had cardiopulmonary
      resuscitation (CPR), endotracheal tube intubation, or
      cardioversion/defibrillation in the ED suffered an in-ED mortality of 25.9% (7)
      and an in-hospital mortality of 59.2% (16). The remaining 148 patients who
      received appropriate treatment, except for the above, had a lower in-hospital
      mortality (20.28%, 30 patients) (p < 0.05). We should limit the number of
      patients in the observation unit to avoid overloading, and classify patients
      according to their clinical conditions. We should determine whether or not they
      have definite diagnoses or are waiting for hospital admission while receiving
      simple treatments. The observation unit must be provided with well-trained staff
      and suitable physical facilities with support services, and rapid specialty
      consultations must be available.

PMID- 15261351
TI  - Emergency Department evaluation of patients with fever and chemotherapy-induced
      neutropenia.
AB  - We sought to describe the common causes of infection in patients presenting to
      the Emergency Department (ED) with elevated temperature and chemotherapy-induced
      neutropenia and to determine the frequency with which the ED diagnosis of
      infection is consistent with the final hospital discharge diagnosis. We performed
      a structured restrospective chart review of ED patients with fever (T > 38
      degrees C) and neutropenia (absolute neutrophil count < 1000/mm(3)) over a 2-year
      period. Fifty-five episodes of neutropenic fever occurred in 52 patients (mean
      age 52 years, range 18-86 years; 53% men). Twenty-six patients (47%) were found
      to have a specific infection identified. Of these, 21/26 (81%; 95% CI, 70-91%)
      had the source of infection identified while in the ED. All patients who had a
      focal site of infection identified during their hospitalization were diagnosed in
      the ED (100%; 95% CI, 86-100%). The other 5 patients, without a source identified
      in the ED, were found to have bacteremia. The 29 patients without a source
      identified in the ED were hospitalized and had negative blood and urine cultures
      and were discharged to home after resolution of fever. A thorough history,
      physical examination, chest radiograph and urinalysis in the ED identified all
      patients with a focus of infection. Meticulous ED evaluation of patients with
      neutropenia and fever may be sufficient to diagnose most sources of infection;
      however, a significant number of patients without an identifiable focus may have
      bacteremia.

PMID- 15261352
TI  - Electrocardiographic findings in Emergency Department patients with pulmonary
      embolism.
AB  - To assess the pre-study, null hypothesis that there is no difference in the
      electrocardiogram (EKG) findings for Emergency Department (ED) patients who rule
      in vs. rule out for suspected pulmonary embolism, a retrospective review of a
      cohort of patients with pulmonary embolism and their controls was conducted in an
      academic, suburban ED. Patients who were evaluated in the ED during a one-year
      study period for symptoms suggestive of pulmonary embolism were eligible for
      inclusion. All patients with pulmonary embolism and sex- and age-matched controls
      comprised the final study groups. Two board-certified cardiologists reviewed each
      patient's EKG. There were 350 eligible patients identified; 49 patients with
      pulmonary embolism and 49 controls were entered into the study. The most common
      rhythm observed in both groups was normal sinus rhythm (67.3% cases vs. 68.6 %
      controls; p = 1.0). Abnormalities believed to be associated with pulmonary
      embolism occurred with similar frequency in both case and control groups (sinus
      tachycardia [18.8 % vs. 11.8%, respectively; p = 0.40]), incomplete right bundle
      branch block (4.2% vs. 0.0%, respectively; p = 0.24), complete right bundle
      branch block (4.2% vs. 6.0, respectively; p = 1.0), S1Q3T3 pattern (2.1 vs. 0.0,
      respectively; p = 0.49), S1Q3 pattern (0.0 vs. 0.0), and extreme right axis (0.0
      vs. 0.0). New EKG changes were identified more frequently for patients with
      pulmonary embolism (33.3% vs. 12.5% controls; p = 0.03), but specific findings
      were rarely different between cases and controls. In our cohort of ED patients,
      we did not identify EKG features that are likely to help distinguish patients
      with pulmonary embolism from those who rule out for the disease.

PMID- 15261353
TI  - Generalized vaccinia in a deployed military member.
AB  - This case report demonstrates the clinical progression of a case of lesions
      consistent with generalized vaccinia after primary vaccination in an otherwise
      healthy adult. The photographs document the appearance and natural course. The
      progression of the lesions is discussed, documenting the natural progression of
      the disease. This case report includes photographs of the oral lesions consistent
      with generalized vaccinia. Oral generalized vaccinia lesions are not well
      documented in the current medical literature.

PMID- 15261354
TI  - Spontaneous multiple cervical artery dissection: two case reports and a review of
      the literature.
AB  - Although spontaneous cervical artery dissection (CAD) is an uncommon cause of
      stroke in the general population, it accounts for 10-25% of cerebrovascular
      events in young to middle-aged patients. Two or more vessels are involved in
      fewer than 15% of dissections, but multiple spontaneous CADs are likely to be
      underestimated owing to frequent spontaneous recanalization and the possible
      oligo-symptomatic presentation. An extensive review of the literature shows that
      in the last 30 years only 28 cases of multiple CADs have been reported, and that
      in half of these patients symptoms were minor and transient. We describe two
      cases of multiple spontaneous CADs presenting as transient ischemic attack (TIA),
      in which only a specific diagnostic flow-chart allowed us to recognize multiple
      vessel involvement and start the appropriate therapy.

PMID- 15261355
TI  - Undiagnosed Takayasu's arteritis mimicking an acute aortic dissection.
AB  - Takayasu's arteritis (TA) is a vasculitis involving the aorta and its branches.
      We report a case of undiagnosed TA that presented to the Emergency Department
      with a chief complaint of chest pain and signs consistent with an aortic
      dissection.

PMID- 15261356
TI  - Spontaneous uterine rupture as an unusual cause of abdominal pain in the early
      second trimester of pregnancy.
AB  - A case of placenta percreta causing spontaneous uterine rupture is presented.
      This is a rare condition, which may present in the antepartum period as abdominal
      pain, with or without signs of hemorrhagic shock. This entity can lead to
      significant morbidity and mortality if not aggressively managed. A discussion
      follows on the pathophysiology, incidence, risk factors, presentation and
      management of this condition.

PMID- 15261357
TI  - Intentional bupropion overdoses.
AB  - Bupropion is an antidepressant that has recently seen increased usage in smoking
      cessation. This increased usage, along with its potential for causing seizures,
      has renewed interest among clinicians about the effects of this drug. The purpose
      of this study is to describe the clinical course of intentional bupropion
      overdoses in adults and adolescents. This study is a retrospective review of
      intentional bupropion overdoses reported to regional poison centers over a 2-year
      period. Our review included 385 cases. Women accounted for 63% of cases and ages
      ranged from 12 to 57 years. Significant clinical effects were noted in 26% of
      cases. Seizures were reported in 11% of patients. Seizures occurred within 6 h in
      most patients. Other prominent effects included tachycardia, agitation, and
      hallucinations. In conclusion, after a bupropion overdose, patients frequently
      display agitation, tachycardia, hallucinations and seizures. Seizures commonly
      occur within 6 h of the ingestion. However, seizures may occur beyond this time
      frame, particularly if persistent tachycardia, agitation, or hallucinations are
      noted.

PMID- 15261358
TI  - Electrocardiographic manifestations: electrolyte abnormalities.
AB  - Because myocyte depolarization and repolarization depend on intra- and
      extracellular shifts in ion gradients, abnormal serum electrolyte levels can have
      profound effects on cardiac conduction and the electrocardiogram (EKG). Changes
      in extracellular potassium, calcium, and magnesium levels can change myocyte
      membrane potential gradients and alter the cardiac action potential. These
      changes can result in incidental findings on the 12-lead EKG or precipitate
      potentially life-threatening dysrhythmias. We will review the major
      electrocardiographic findings associated with abnormalities of the major cationic
      contributors to cardiac conduction-potassium, calcium and magnesium.

PMID- 15261359
TI  - Event medicine: injury and illness during an expedition-length adventure race.
AB  - To describe the incidence and type of injury and illness occurring during an
      expedition-length adventure race and identify those resulting in withdrawal from
      the event, a prospective cohort study was conducted of the injuries and illness
      treated during the Subaru Primal Quest Expedition Adventure Race trade mark held
      in Colorado July 7-16, 2002. All racers, support crewmembers, and race staff were
      eligible to participate in the study. When a member of the study group received
      medical care due to an injury or illness, the encounter was recorded on a Medical
      Encounter Form. If an injury or illness resulted in withdrawal from the race,
      this was also recorded. Information from the Medical Encounter Forms was used to
      generate the Medical Log. There were 671 individuals eligible to participate in
      the study. A total of 243 medical encounters and 302 distinct injuries and
      illnesses were recorded. There were 179 (59%) injuries and 123 (41%) illnesses.
      Skin and soft tissue injuries and illness were the most frequent (48%), with
      blisters on the feet representing the single most common (32.8%). Second was
      respiratory illness (18.2%), including upper respiratory infection, bronchitis
      and reactive airway disease-asthma. Respiratory illness was the most common
      medical reason for withdrawal from the event. Injuries accounted for almost 60%
      of all injury and illness yet they contributed to less than 15% of the medical
      withdrawals from the race. Blisters accounted for almost one-third of all
      conditions treated. Providers of medical support for expedition-length adventure
      races should be prepared to treat a wide variety of injury and illness.

PMID- 15261360
TI  - The wrist pivot method, a novel technique for temporomandibular joint reduction.
AB  - Temporomandibular joint (TMJ) dislocation is an infrequent dislocation of the
      mandible. The usual technique of reduction, recommended by most Emergency
      Medicine textbooks, consists of downward forces applied to the mandible. In the
      authors' experience this is often painful and requires significant sedation. We
      present a patient in whom the usual manner of TMJ dislocation reduction was
      difficult. We describe a novel technique for TMJ dislocation reduction that uses
      the intrinsic biomechanical properties of the mandible.

PMID- 15261361
TI  - Shortness of breath in the postoperative patient.

PMID- 15261362
TI  - EKG findings associated with situs inversus.

PMID- 15261363
TI  - A unique pattern of injury secondary to seatbelt-related blunt abdominal trauma.

PMID- 15261364
TI  - Diagnosis of appendicitis with ultrasound: case example.

PMID- 15261365
TI  - Growing pains.

PMID- 15261366
TI  - The ten commandments of pediatric Emergency Medicine.

PMID- 15261367
TI  - Observation and critical care in the emergency department: watch what you do!

PMID- 15261370
TI  - [Acinetobacter baumannii, the nosocomial pathogen par excellence].

PMID- 15261368
TI  - Re: Cerebral and coronary air embolism: an intradepartmental suicide attempt.; J
      Emerg Med. 2003 Jul;25(1):29-34.

PMID- 15261371
TI  - Potential cell therapy of heart failure.

PMID- 15261372
TI  - [Anethole dithiolethione: an antioxidant agent against tenotoxicity induced by
      fluoroquinolones].
AB  - Tendinopathy and tendon rupture are the adverse effects observed with
      fluoroquinolone antibiotics in old patients. The aim of this study was to
      investigate the effect of anethole dithiolethione (5-[p-methoxyphenyl]3H-1,2
      dithiole-3-thione) on the oxidative stress induced by three fluoroquinolones
      (pefloxacin, ofloxacin, ciprofloxacin) incubated with rabbit tenocyte cell line.
      Anethole dithiolethione is a well known antioxidant and glutathione inducer.
      Anethole dithiolethione is widely used in human therapy for its choleretic,
      sialogogic properties and recently proposed as cytoprotective agent in lung
      precancerous lesions prevention in smokers. In this purpose, protection against
      oxidative stress induced by fluoroquinolones has been assessed using
      cytofluorimetric probes to quantify cytotoxicity and reactive oxygen species
      production. Fluorescence signal was quantified in 96-well microplates, using cold
      light cytofluorometer. Significant reactive oxygen species production was
      detected after 45 minutes for all fluoroquinolones tested. Anethole
      dithiolethione has been evaluated on this parameter. Anethole dithiolethione
      significantly (*: P<0.05) reduces and normalizes reactive oxygen species induced
      by fluoroquinolones. So, anethole dithiolethione (Sulfarlem), well known for its
      antioxidant and glutathione inducing properties, good tissue diffusion and good
      tolerance in humans, could be beneficially associated to fluoroquinolones, and be
      proposed as a therapeutic adjuvant to prevent oxidative stress and tendinous
      adverse effects induced by xenobiotics and more precisely by fluoroquinolones.

PMID- 15261373
TI  - [The flavonoids effect against vinblastine, cyclophosphamide and paracetamol
      toxicity by inhibition of lipid-peroxydation and increasing liver glutathione
      concentration].
AB  - The paracetamol and cyclophosphamid are metabolized in the liver by the
      cytochrome P450. The formed reactive intermediates are responsible of a
      hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is
      also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoids
      are polyphenols substances of plant origin having some biological and anti
      oxydative properties. However no information is available on their effects on
      glutathion and glutathion-s-transferases. In our research, we valued the effect
      of oral administration of flavonoids (diosmine and quercetine) under shape of
      propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic
      toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way,
      vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the
      paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the
      rat female albinos wistar. We did a blood numeration, an assessment of serum
      activities of transaminases and alkali phosphatases as well as quantification of
      the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated.
      Analyses are done at regular intervals; 1, 3, 7 and 14 days after the
      administration of drugs. In the group of rats treated by the cyclophosphamid
      paracetamol alone we observed since the 1st day, an increase of lipid peroxide
      (MDA) of 120% and a downfall of hepatic glutathion including the group receiving
      the vinblastine (until 210% of reduction). In the same way a severe leucopenia
      and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th
      day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and
      vinblastine). The combination of flavonoids with drugs have clearly reduced the
      effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as
      well as the leucopenia and thrombopenia of the cyclophosphamide are corrected
      entirely. In the same way, we noted a restoration of rates of peroxide and
      glutathion. Flavonoids seem to act by activation of the turn over of the
      glutathion and enzymes stimulating particularly glutathion-s-transferases
      permitting the captation of the reactive metabolites of the studied drugs.

PMID- 15261374
TI  - [High prevalence and incidence of hepatitis C virus infections among dialysis
      patients in the East-Centre of Tunisia].
AB  - Hemodialysed patients are recognised as a group at increased risk of infection
      with hepatitis C virus (HCV). The aim of this study was to determine the
      prevalence and incidence of HCV infection among dialysis patients of the east
      centre part of Tunisia. Two hundred and seventy-six patients dialysed until 2001
      were recruited within seven hemodialysis units located in the cities of Sousse,
      Monastir and Mahdia. The serum markers of HCV infection were tested over the
      period of March 2000-December 2002, by a 3rd generation ELISA test for antibodies
      and by qualitative RT-PCR technique for viral RNA. The prevalence of anti-HCV
      antibodies and of HCV RNA was 32.6% (90 patients) and 25.7% (71 patients),
      respectively. Between 1998 and 2002, 20 new infections were documented in five of
      the seven dialysis units corresponding to an incidence of 2.34% per year, with an
      average time of contamination after the beginning of dialysis of 4.6 years. If
      all the infections are assessed to have occurred during dialysis, the density of
      incidence of HCV contamination was 4.4% per year of dialysis. A high correlation
      was noticed between the presence of HCV markers in serum and the duration of
      dialysis (F = 34.15, P < 0.0001). In the absence of other risk factors
      (transfusion, drug-addiction), these results plead for the nosocomial
      transmission of the observed HCV infections. A phylogenetic analysis of the E2
      hypervariable region of the viral genome is in progress to confirm this
      assumption.

PMID- 15261375
TI  - [hScrib: a potential novel tumor suppressor].
AB  - Establishment and maintenance of epithelial cell polarity rely on finely tuned
      protein networks comprising cell surface molecules, cytoplasmic adaptors, and
      enzymes connected to the actin cytoskeleton. Oncogenes and tumor suppressors
      promote cell proliferation and resistance to apoptosis and, in many cases, alter
      some of these molecular scaffolds, and profoundly affect the epithelial
      cytoarchitecture. Reciprocally, loss of central actors of epithelial polarity
      unleashes normally repressed signaling pathways and perturb the shape and
      functions of epithelial tissues. Among the newcomers impacting on epithelial
      integrity, Scribble is a scaffold protein of a remarkable importance that
      furthermore displays a tumor suppressing activity in Drosophila melanogaster.
      Together with Discs Large (Dlg) and Lethal Giant Larvae (Lgl), two known tumor
      suppressors, Scribble acts on the correct positioning of epithelial junctions
      required to organize functional epithelial sheets. Scribble, Dlg and Lgl proteins
      are well conserved during evolution at the molecular and subcellular level
      implying their potential role in cell polarity and tumorigenesis in humans.
      Recent findings on hScrib, the human orthologue of Scribble, are discussed here.

PMID- 15261376
TI  - [Pharmacogenetics and pharmacogenomics of cancers].
AB  - Sequencing the human genome brings new tools for the individualisation of cancer
      chemotherapy, firstly thanks to the identification of polymorphisms of genes
      involved in anticancer drug metabolism or activity (Pharmacogenetics), and
      secondly thanks to the determination of tumour gene expression profiles and their
      relationship to chemosensitivity and chemoresistance (Pharmacogenomics). A few
      functional polymorphisms have been known for a long time (thiopurine
      methyltransferase, glutathion S-transferases), but several new ones have been
      identified recently, at the level of the genes encoding drug targets (thymidylate
      synthase), at the level of DNA repair enzymes (XPD) or at the level of transport
      proteins (MDR1). On the other hand, the research of correlations between gene
      expression profiles and chemosensitivity has been performed on the in vitro
      models of the National Cancer Institute and may allow crucial improvements in the
      identification of patients who would best take advantage of a specific
      chemotherapy. Clinical trials, first on a retrospective basis, then on a
      prospective one, are implemented to validate this approach.

PMID- 15261377
TI  - Huntington's disease: how does huntingtin, an anti-apoptotic protein, become
      toxic?
AB  - Huntington's disease belongs to a class of inherited neurological disorders that
      are caused by the presence of a polyglutamine expansion in apparently unrelated
      proteins. In Huntington's disease, expansion occurs in the huntingtin protein.
      Together with the characteristic formation of aggregates in the diseased state,
      several post-translational modifications affect huntingtin during the
      pathological process and lead to the dysfunction and eventual death of selective
      neurons in the brain of patients. These mechanisms are not completely described
      but could involve the gain of a new toxic function as well as the loss of the
      beneficial properties of huntingtin.

PMID- 15261378
TI  - [Gaucher disease: clinical, genetic and therapeutic aspects].
AB  - Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and
      one of the rare genetic diseases for which therapy is now available. Partial
      deficiency of glucocerebrosidase is associated with parenchymal disease of the
      liver, spleen, and bone marrow with concomitant anaemia and thrombocytopenia in
      non-neuronopathic, type 1, Gaucher disease. Severe deficiency of
      glucocerebrosidase caused by disabling mutation is additionally associated with
      neurological manifestations in the less common type 2 and type 3 Gaucher
      diseases. Outside of the Ashkenazi Jewish community, a high molecular diversity
      is observed. Clarification of genotype-phenotype relationship and the
      identification of modifier loci that impact on Gaucher disease phenotypes remain
      a critical area for research. Recombinant glucocerebrosidase (imiglucerase) is an
      effective mean of treating type 1 Gaucher disease and should be initiated early
      on in life. Amelioration of hepatosplenomegaly and of haematological
      manifestations is usually apparent within six months. Bone disease responds more
      slowly. Imiglucerase has recently been approved for the treatment of type 3
      Gaucher disease. Enzyme replacement therapy cannot reverse the neurological
      deficits in type 2 or type 3 Gaucher disease. This should prompt further research
      on substrate deprivation and gene therapy.

PMID- 15261379
TI  - [Monoclonal antibodies and therapeutics].
AB  - More than 25 years after their discovery, monoclonal antibodies are now the most
      rapid expanding pharmaceutical viable drugs in clinical trials. The emergence of
      these antibodies was made possible by the development of genetic recombinant
      techniques. It is now possible to obtain engineered antibodies: chimearic or
      humanized or fully human monoclonal antibodies via the use of phage display
      technology or of transgenic mice. These antibodies are tolerable to the human
      immune system and eleven have been approved for therapeutic by the US Food and
      Drug Administration (FDA), the majority of them in the past four years. At least
      an additional 400 monoclonal antibodies are in clinical trials to treat cancer,
      transplant rejection or to combat autoimmune or infectious diseases. Important
      advances have been made in the design of highly specific fragment antibodies,
      fused or not with drugs or radioisotopes, and in the large industrial scale
      production with different expression systems (bacteria, yeasts, mammalian cells
      and transgenic plants and animals). In the next future new molecular promising
      strategies will enhance affinity, stability and expression levels and reduce the
      price of these engineering monoclonal to permit their use to treat a large number
      of diseases.

PMID- 15261380
TI  - The Goodeniaceae.
AB  - The Goodeniaceae family contributes some of the more spectacular wildflowers
      found on the Australian continent. The bright and vibrant colours that
      characterise members of the family has attracted much horticultural interest. A
      number of species have traditionally been used for medicinal purposes by
      indigenous communities, and the phytochemistry of some has been investigated.
      These aspects are considered in this review to determine correspondence between
      the reputed medicinal effects and the bioactivity of the secondary metabolites
      produced.

PMID- 15261381
TI  - Myorelaxant and antispasmodic effects of the aqueous extract of Mitragyna inermis
      barks on Wistar rat ileum.
AB  - Mitragyna inermis is used in the Senegal traditional medicine for treating
      stomach and intestinal disorders. At concentrations of 0.5, 0.75 and 1 mg/ml, the
      aqueous extract of M. inermis bark (AEMIB) significantly induced a decrease of
      the ileal basal tonus, respectively, from 37+/-1, 51+/-1 and 75+/-2% (P<0.05;
      n=5), compared to the baseline values. As well as atropine, AEMIB inhibited
      submaximal contractions induced by 0.01 mg/ml ACh with IC(50) value of
      approximately 0.75 mg/ml (n=5). These results show that AEMIB possesses both
      myorelaxant and antispasmodic actions in the ileum. This may justify the
      pharmacological basis for the popular use of Mitragyna for the treatment of
      gastrointestinal disorders.

PMID- 15261382
TI  - Anti-Helicobacter pylori metabolites from Rhizoctonia sp. Cy064, an endophytic
      fungus in Cynodon dactylon.
AB  - A new benzophenone, named rhizoctonic acid (1), together with three known
      compounds monomethylsulochrin (2), ergosterol (3) and 3beta,5alpha,6beta
      trihydroxyergosta-7,22-diene (4) were isolated through bioassay-guided
      fractionations from the culture of Rhizoctonia sp. (Cy064), an endophytic fungus
      in the leaf of Cynodon dactylon. The structure of the new acid 1 was elucidated
      to be 5-hydroxy-2-(2-hydroxy-6-methoxy-4-methylbenzoyl)-3-methoxybenzoic acid by
      a combination of spectral analyses. Furthermore, the structure of
      monomethylsulochrin 2 was confirmed by 13C-NMR analysis. All four metabolites
      were subjected to a more detailed in vitro assessment of their antibacterial
      action against five clinically isolated and one reference (ATCC 43504)
      Helicobacter pylori strains.

PMID- 15261383
TI  - Anxiolytic effects of Echium amoenum on the elevated plus-maze model of anxiety
      in mice.
AB  - The ethanolic extract of Echium amoenum flowers at the dose of 50 mg/kg increased
      the percentage of time-spent and the percentage of arm entries in the open arms
      of the elevated plus-maze (EPM) and decreased the percentage of time-spent in the
      closed arms of EPM. Moreover, it prolonged the ketamine-induced latency to sleep
      but had no significant effects on total sleeping time induced by ketamine. Also,
      the locomotor activity was affected but not to the same extent as observed for
      diazepam. These results suggested that the extract of E. amoenum seems to possess
      anxiolytic effect with lower sedative activity than that of diazepam.

PMID- 15261384
TI  - Isolation and biological properties of polysaccharide CPS-1 from cultured
      Cordyceps militaris.
AB  - A polysaccharide from the water extract of cultured Cordyceps militaris was
      isolated through ethanol precipitation, deproteination and gel-filtration
      chromatography. Their molecular weight was determined using gel-filtration
      chromatography. The structure of polysaccharide CPS-1 was elucidated by sugar
      analysis, Smith degradation, IR and 13C-NMR spectroscopy. CPS-1 was shown to
      possess a significant antiinflammatory activity and suppressed the humoral
      immunity in mice but had no significant effects on the cellular immunity and the
      non-specific immunity.

PMID- 15261385
TI  - Intermediate reactive oxygen and nitrogen from macrophages induced by Brazilian
      lichens.
AB  - The activity of ten compounds isolated from Brazilian lichen over the release of
      hydrogen peroxide and nitric oxide was evaluated in the culture of peritoneal
      macrophage cells from mice. Salazinic, secalonic A and fumarprotocetraric acids
      were the compounds that induced the greatest release of H2O2, whereas 12R-usnic
      and diffractaic acids induced the release of NO. These results indicate that
      lichen products have potential immunological modulating activities.

PMID- 15261386
TI  - Proteolytic properties of Funastrum clausum latex.
AB  - As part of a screening of latex endopeptidases from plants growing in Argentina,
      the presence of proteolytic activity in the latex of Funastrum clausum stems is
      reported. The proteases present in the crude extract showed the main
      characteristics of the cysteine proteolytic class, i.e. optimum pH at alkaline
      range, isoelectric point (pI) higher than 9.0, and inhibition of proteolytic
      activity by thiol blocking reagents. A remarkable thermal stability was also
      evident in the crude extract. Endosterolytic preference tried on p-nitrophenyl
      esters of N-alpha-carbobenzoxy-L-amino acids was higher for the alanine,
      asparagine and tyrosine derivatives. Preliminary peptidase purification by two
      step ionic exchange showed the presence of two proteolytic fractions with
      molecular masses of approximately 24.0 kDa according to SDS-PAGE.

PMID- 15261387
TI  - Antibacterial activity of Galeola foliata.
AB  - Galeola foliata leaves and stem bark were successively extracted with petrol,
      dichloromethane, ethyl acetate, butanol and methanol. A broad spectrum
      antibacterial activity (24 bacteria and protozoan) was exhibited by both parts. A
      very good level of activity was demonstrated by the CH2Cl2 and EtOAc fractions.
      None of the fractions were active against the moulds.

PMID- 15261388
TI  - Xanthone isolated from Securidaca longependunculata with activity against
      erectile dysfunction.
AB  - 1,7-Dimethoxy-2-hydroxy-xanthone and 1,4-dihydroxy-7-methoxy-xanthone isolated
      from Securidaca longependunculata were tested for their activity on rabbit corpus
      cavernosum in vitro. Only the former relaxed the corpus cavernosum by 63% at 1.8
      x 10(-5) mg/ml.

PMID- 15261389
TI  - Cytotoxic constituents from Plumbago zeylanica.
AB  - The bioassay-guided fractionation of the dichloromethane extract of aerial parts
      of Plumbago zeylanica led to the isolation of beta-sitosterol, beta-sitosteryl
      3beta-glucopyranoside, beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (1),
      lupenone, lupeol acetate, plumbagin and trilinolein. Compound 1 showed cytotoxic
      activity against MCF7 and Bowes cancer cell lines (IC50 113 microM and 152
      microM, respectively), beta-sitosterol inhibited Bowes cell growth (IC50 36.5
      microM) and plumbagin was cytotoxic against MCF7 and Bowes cells (IC50 1.28
      microM and 1.39 microM, respectively).

PMID- 15261390
TI  - Growth responses of Cassia obtusifolia toward human intestinal bacteria.
AB  - 1,2-Dihydroxyanthraquinone (1) was isolated from the seed of Cassia obtusifolia
      through bioassay-guided fractionation. 1,2-Dihydroxyanthraquinone strongly
      inhibited the growth of Clostridium perfringens and Escherichia coli. Structure
      activity relationship revealed that 1,4-dihydroxyanthraquinone (2) and 1,8
      dihydroxyanthraquinone (3) had strong growth-inhibition against C. perfringens.
      In growth-promoting activity, 1,2-, 1,4-, and 1,8-dihydroxyanthraquinones
      exhibited strong growth-promoting activity to Bifidobacterium bifidum.

PMID- 15261391
TI  - Antibacterial activity and cytotoxicity of extractives from Ravenia spectabilis.
AB  - A methanolic extract of Ravenia spectabilis, an isolated alkaloid, arborinine
      plus a fraction comprising arborinine and gamma-fagarine (VLC), showed mild to
      significant in vitro antibacterial activity. In a brine shrimp lethality
      bioassay, the extract and the fraction were found to exhibit moderate
      cytotoxicity having LC50 of 76.26 microg/ml and 14.98 microg/ml, respectively.

PMID- 15261392
TI  - Antimicrobial activity of extracts and some compounds from Calea platylepis.
AB  - The antimicrobial activity of dichloromethane extracts (leaves, flowers and
      underground parts) and some compounds isolated from Calea platylepis were
      evaluated by the well diffusion method.

PMID- 15261393
TI  - 6-Phenylpyrones and 5-methylchromones from Kenya aloe.
AB  - Two new compounds, 10-O-beta-D-glucopyranosyl aloenin (4) and 8-C-beta-D
      glucopyranosyl-7-O-methyl-(R)-aloesol (6), were isolated from a commercial sample
      of Kenya aloe together with the known products aloenin (2), aloenin 2'-p
      coumaroyl ester (3), aloenin aglycone (1), orcinol and acetylorcinol. All
      structures were determined or confirmed by spectral analyses.

PMID- 15261394
TI  - Rings, chains and ladders: ubiquitin goes to work in the neuron.
AB  - Our understanding of neuronal cell biology in the last 10 years has exploded. In
      parallel, our grasp of basic cellular processes, such as protein synthesis and
      protein degradation has also grown exponentially. In this review, we provide an
      in-depth background to details of current knowledge of the Ub/proteasome pathway.
      We also provide examples of recent experiments in neurobiology that suggest a
      central role for targeted protein degradation by the Ub/proteasome pathway to
      ensure proper neuronal function. From the examples provided, it is clear the
      activity of the proteasome is required for neuronal pathfinding during
      development, regulation of synaptic branching and number, and synaptic
      plasticity. We conclude with a discussion of how defects in proteasome pathway
      function may lead to neuronal dysfunction, with specific emphasis on diseases
      characterized by the accumulation of ubiquitin (Ub)-positive inclusions. Our goal
      is to excite the expert neurobiologist to the myriad ways that specific neuronal
      functions could be regulated (or dysregulated) by mechanisms involving the
      Ub/proteasome pathway.

PMID- 15261395
TI  - Basic organization principles of the VOR: lessons from frogs.
AB  - Locomotion is associated with a number of optical consequences that degrade
      visual information processing in the absence of appropriate compensatory
      movements. The resulting retinal image flow is counteracted by coordinated eye
      head reflexes that are initiated by optokinetic and vestibular inputs. The
      contribution of the vestibulo-ocular reflex (VOR) for stabilizing retinal images
      is relatively small in amplitude in frogs but important in function by
      compensating for the non-linearities of the neck motor system. The spatial tuning
      of the VOR networks underlying the angular (AVOR) and linear (LVOR) with respect
      to canal and extraocular motor coordinates is organized in a common, canal
      related reference frame. Thereby, the axes of head and eye rotation are aligned,
      principle and auxiliary VOR connections transform vestibular into motor signals
      and parallel AVOR and LVOR circuits mediate vergence and version signals
      separately. Comparison of these results with data from other vertebrates
      demonstrates a number of fundamental organization principles common to most
      vertebrates. However, the fewer degrees of behavioral freedom of frogs are
      reflected by the absence of, e.g. a functioning velocity storage network or of a
      fixation suppression of the VOR. In vitro experiments with the isolated brainstem
      and branches of N.VIII attached were used to study the putative transmitters of
      vestibular nerve afferent inputs, the postsynaptic receptor subtypes of second
      order vestibular neurons and their dynamic response properties. Evidence is
      presented that suggests that afferent vestibular nerve fibers with different
      dynamic response properties activate different subtypes of glutamate receptors.
      The convergence pattern of monosynaptic afferent nerve inputs from different
      labyrinthine organs onto second-order vestibular neurons is remarkably specific.
      As a rule, second-order vestibular neurons receive converging afferent nerve
      inputs from one semicircular canal and from a specific sector of hair cells on
      one otolith organ. This convergence pattern remains malleable even in adulthood
      and reorganization is initiated by activity-related changes in vestibular nerve
      afferent fibers. The output of second-order vestibular neurons is modified by at
      least three inhibitory control loops. Uncrossed inhibitory vestibular side loops
      appear to control specifically the dynamic response tuning, whereas coplanar
      commissural inhibitory inputs improve mainly the spatial tuning and the
      cerebellar feedback loop controls the response gain. Among the targets of second
      order vestibular projection neurons are extraocular motoneurons and internuclear
      neurons. Extraocular motoneurons differ among each other by the presence of very
      different response dynamics. These differences may represent a co-adaptation to
      the response dynamics of twitch and non-twitch extraocular muscle fibers.
      Different dynamical properties are required for a rapid acceleration of the globe
      at the one end and for the maintenance of a stable eccentric eye position over
      long periods of time at the other end of a continuum of variations in dynamic
      response properties. The maintenance of a given eccentric eye position over long
      periods of time is especially well developed in frogs and assists visual
      surveillance during lurking in the absence of saccades.

PMID- 15261396
TI  - Thiol synthesis and arsenic hyperaccumulation in Pteris vittata (Chinese brake
      fern).
AB  - Pteris vittata (Chinese brake fern) has potential for phytoremediation of As
      contaminated sites. In this study, the synthesis of total thiols and acid-soluble
      thiols in P. vittata was investigated under arsenic exposure. The strong and
      positive correlation between As concentration and acid-soluble thiols in plant
      leaflets suggests that acid-soluble thiols may play a role in As detoxification.
      A major As-induced thiol was purified and characterized. A molecular ion (M + 1)
      of 540 m/z suggests that the thiol was a phytochelatin (PC) with two base units
      (PC(2)). However, the ratios of acid-soluble thiols to As in leaflets exposed to
      As ranged from 0.012 to 0.026, suggesting that only a very small part of As is
      complexed by PC(2). PCs could play a minor detoxification role in this
      hyperaccumulator. A PC-independent mechanism appears to be mainly involved in As
      tolerance, while PC-dependent detoxification seems to be a supplement.

PMID- 15261397
TI  - The effect of ozone on pollen development in Lolium perenne L.
AB  - Perennial ryegrass plants (Lolium perenne L.) were exposed in "Closed-Top
      Chambers" to different ozone concentrations and to charcoal filtered ambient air
      to study the effect of ozone on the development of pollen. Ozone at ambient (65
      nl l(-1), 8h) and elevated (110 nl l(-1), 4h) concentrations affected the
      maturing of pollen by inhibiting starch accumulation in pollen throughout the
      anther. Affected pollen persisted in the vacuolated state while normal pollen in
      the same anther were filled with amyloplasts. The percentage of underdeveloped
      pollen-determined in transversal sections-was significantly higher in exposed
      plants than in plants grown in filtered air. Results indicate that ozone stress
      was responsible for the disrupted development of pollen in L. perenne.

PMID- 15261398
TI  - Evaluation of the BCR sequential extraction procedure applied for two unpolluted
      Spanish soils.
AB  - The procedure of BCR sequential extraction has been applied to five samples from
      two unpolluted soils in southern Spain. Total concentrations of different
      elements have been calculated as the sum of the three fractions of BCR and the
      residue has been measured for each. Also, a total analysis based on INAA or total
      digestion techniques has been performed for the same samples. BCR and total
      analysis closely agreed for As, Pb and Cd. For Cu, Co, Cr and Zn the comparison
      of the results did not provide definitive conclusions concerning the capability
      of BCR in measuring total concentrations. On the other hand, in these cases, a
      certain correlation was found between the concentrations measured and some soil
      characteristics, especially the clay, organic-matter and CaCO(3) contents. BCR
      proved incapable of providing accurate measurements for Ni.

PMID- 15261399
TI  - The effects of the contemporary-use insecticide (fipronil) in an estuarine
      mesocosm.
AB  - To examine the effects of environmentally realistic fipronil concentrations on
      estuarine ecosystems, replicated mesocosms containing intact marsh plots and
      seawater were exposed to three treatments of fipronil (150, 355, and 5000 ng/L)
      and a Control. Juvenile fish (Cyprinidon variegatus), juvenile clams (Mercenaria
      mercenaria), oysters (Crassostrea virginica), and grass shrimp (Palaemonetes
      pugio) were added prior to fipronil in an effort to quantify survival, growth,
      and the persistence of toxicity during the planned 28-day exposure. Results
      indicated that there were no fipronil-associated effects on the clams, oysters,
      or fish. Shrimp were sensitive to the highest two concentrations (40% survival at
      355 ng/L and 0% survival at 5000 ng/L). Additionally, the highest fipronil
      treatment (5000 ng/L) was toxic to shrimp for 6 weeks post dose. These results
      suggest that fipronil may impact shrimp populations at low concentrations and
      further use in coastal areas should be carefully assessed.

PMID- 15261400
TI  - Relationships between metal concentrations in great tit nestlings and their
      environment and food.
AB  - Metal concentrations (Ag, As, Cd, Cu, Hg, Ni, Pb, Zn) were determined in the
      feathers and excreta of nestling great tits (Parus major), in their main
      invertebrate prey (Lepidoptera larvae) and in vegetation samples, all collected
      from four sites along a pollution gradient. Metal contamination in vegetation
      samples increased significantly towards the pollution source. The Ag, As, Hg, Ni
      and Pb concentrations in food samples were significantly higher at the site
      closest to the pollution source compared to the other three sites. Great tit
      nestlings from the site closest to the pollution source had significantly higher
      concentrations of Ag, As, Hg and Pb in their excreta than did nestlings at the
      other three sites. For five metals (Ag, As, Cu, Ni and Pb), we found
      concentrations in caterpillars to be significantly positively correlated with
      vegetation samples. We also found clear significant positive correlations between
      excreta and caterpillars for Ag, As, Hg and Pb and between feathers and
      caterpillars for As and Pb. Our data suggest that excreta are a good monitor for
      the presence and concentrations of non-essential metals in the food and the
      environment of passerine birds.

PMID- 15261401
TI  - Persistent organochlorines in human breast milk collected from primiparae in
      Dalian and Shenyang, China.
AB  - The present study determined the concentrations of organochlorines (OCs) such as
      polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its
      metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds
      (CHLs), hexachlorobenzene (HCB) and tris(4-chlorophenyl)methane (TCPMe) in human
      breast milk collected from primiparae in Dalian and Shenyang, northeastern China
      during 2002. In addition, dioxins and related compounds in pooled samples of
      human breast milk from Dalian and Shenyang were also analyzed. OCs were detected
      in all the human breast milk samples analyzed in this study. The predominant
      contaminants in human breast milk were HCHs, DDTs and HCB, and the levels were
      relatively higher than those in other countries. On the other hand,
      concentrations of dioxins and related compounds, PCBs, and CHLs were relatively
      low. Concentrations of OCs in human breast milk from Dalian, which is located
      along the coast of Bo Hai Strait, were significantly higher than those from
      Shenyang, implying that the residents in Dalian might be mainly exposed to these
      contaminants from seafood. When the relationship between concentrations of OCs in
      human breast milk and age of primiparae was examined, no significant correlation
      was observed. This might be caused by the limited sample numbers and narrow range
      of mother's age and/or recent ban of DDT and HCH production and use. Significant
      correlation between concentrations of TCPMe and DDTs in human breast milk
      suggested that technical DDT might be a source of TCPMe in the Chinese
      population. When daily intakes of DDTs and HCHs to infants through human breast
      milk were estimated, human breast milk from Dalian showed significantly higher
      contribution than Shenyang, implying that infants in Dalian might be at higher
      risk by these contaminants.

PMID- 15261402
TI  - Manganese uptake and accumulation by the hyperaccumulator plant Phytolacca
      acinosa Roxb. (Phytolaccaceae).
AB  - The perennial herb Phytolacca acinosa Roxb. (Phytolaccaceae), which occurs in
      Southern China, has been found to be a new manganese hyperaccumulator by means of
      field surveys on Mn-rich soils and by glasshouse experiments. This species not
      only has remarkable tolerance to Mn but also has extraordinary uptake and
      accumulation capacity for this element. The maximum Mn concentration in the leaf
      dry matter was 19,300 microg/g on Xiangtan Mn tailings wastelands, with a mean of
      14,480 microg/g. Under nutrient solution culture conditions, P. acinosa could
      grow normally with Mn supplied at a concentration of 8000 micromol/l, although
      with less biomass than in control samples supplied with Mn at 5 micromol/l.
      Manganese concentration in the shoots increased with increasing external Mn
      levels, but the total mass of Mn accumulated in the shoots first increased and
      then decreased. At an Mn concentration of 5000 micromol/l in the culture
      solution, the Mn accumulation in the shoot dry matter was highest (258 mg/plant).
      However, the Mn concentration in the leaves reached its highest value (36,380
      microg/g) at an Mn supply level of 12,000 micromol/l. These results confirm that
      P. acinosa is an Mn hyperaccumulator which grows rapidly, has substantial
      biomass, wide distribution and a broad ecological amplitude. This species
      provides a new plant resource for exploring the mechanism of Mn
      hyperaccumulation, and has potential for use in the phytoremediation of Mn
      contaminated soils.

PMID- 15261403
TI  - Concentrations of organotin compounds in sediment and clams collected from
      coastal areas in Vietnam.
AB  - Levels of butyltin (BT) and phenyltin (PT) compounds were determined in sediments
      and clam Meretrix spp. collected from north and central coastal areas in Vietnam.
      Concentrations of TBT in sediments ranged from 0.89 to 34 ng g(-1) dry wt and
      those in clams ranged from 1.4 to 56 ng g(-1) wet wt. The levels of TBT in
      sediments and clams from Vietnam were within limits reported from other
      countries. Further, the TBT level in clams was lower than the tolerable average
      residue level (TARL) estimated based on tolerable daily intake (TDI). Trace
      amounts of PTs were also found in both sediment and clam samples. In sediments
      from north and central Vietnam, the concentrations of TBT were highest in the
      order of Hue (28 ng g(-1) dry wt), Cua Luc (15 ng g(-1) dry wt), Sam Son (6.3 ng
      g(-1) dry wt), and Tra Co (5.5 ng g(-1) dry wt). Among the clams from north and
      central Vietnam, the levels of TBT in clams from Cua Luc were dramatically high
      at 47 ng g(-1) wet wt. TBT formed the principal butyltin species in sediment at
      all sites studied. The ratios of TBT in sediment were higher among BT compounds
      at all study sites. Of total BTs, TBT was the dominant species in clams from
      almost all sites studied. In spatial distribution, TPT showed a pattern similar
      to TBT, suggesting the use of TPT as an antifouling paint. The partition
      coefficient between sediment and calms was calculated. The partition coefficients
      of TBT and TPT were 2.01 (0.56-5.5) and 9.23 (3.1-20), respectively. These
      results show that sediment-bound TBT is a source of contamination to clams in
      addition to dissolved TBT.

PMID- 15261404
TI  - Interactions of metals affect their distribution in tissues of Phragmites
      australis.
AB  - Culms of Phragmites australis were grown in vermiculite in a greenhouse. Some
      plants were exposed to 1000 microg/g Cu or Pb or Zn, or combinations of two or
      three of those metals. When plants reached senescence, they were harvested and
      analyzed for metal concentrations in upper leaves, lower leaves, stems and roots.
      While all metals accumulated in highest concentrations in the roots, Zn
      accumulated in aboveground tissues far more than the other metals. Furthermore,
      the concentration of any one metal in the different tissues was affected by the
      presence of other metals. The amount of copper in upper leaves increased when Zn
      was also present with the Cu. The amount of Cu in roots was increased in the
      presence of Pb and/or Zn. The amount of Zn in lower leaves was reduced when Cu
      was also present along with Zn. Thus, when combinations of metals were present,
      the distribution of metals was altered. The most important interactions appeared
      to be of Cu and Zn, which may reflect competition for binding sites on metal
      binding proteins.

PMID- 15261405
TI  - Changes in the atmospheric deposition of minor and rare elements between 1975 and
      2000 in south Sweden, as measured by moss analysis.
AB  - Elements emitted to the atmosphere are partly exported to more remote areas and
      contribute to the regional and territorial deposition rates. This study is based
      on the principle that carpet-forming bryophytes (pleurocarpic mosses) absorb
      elements and particles from rain, melting snow and dry deposition. We compare the
      concentrations of 60 elements in carpets of the forest moss Pleurozium schreberi
      sampled in 1975 and 2000 within a sparsely inhabited area dominated by forest and
      bogland in south Sweden. As an average for all the 60 elements, the median
      concentration was 2.7 times higher in 1975 than in 2000. The greatest difference
      was measured for Pb, although In, Bi, Ge, V, Sn, As and Ag had more than 5 times
      higher concentrations in 1975 than in 2000. Somewhat lower 1975/2000
      concentration ratios (3.0-3.8) were measured for U, Sb, Cd, W, Ga, Fe, Li, and
      Be. The rare-earth elements (Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb,
      and Lu), except Eu as well as Th, Ni, Al, Ti, Hf, Nb, and Zr, had concentration
      ratios around the average (2.5-2.8). Possible causes of these changes are
      discussed. We conclude that reductions in anthropogenic dust emissions during
      recent decades have decreased the atmospheric deposition over northern Europe of
      most elements in the periodical system, as previously reported for a limited
      number of transition and heavy metals. Changes in the deposition of soil dust
      would be of minor importance to the decreased deposition rates.

PMID- 15261406
TI  - Organochlorine pesticides and polychlorinated biphenyls in California sea lions.
AB  - Concentrations of polychlorinated biphenyls (PCBs), DDTs, chlordanes, HCHs,
      hexachlorobenzene (HCB), dieldrin, heptachlor epoxide, tris(4
      chlorophenyl)methane (TCPMe), and tris(4-chlorophenyl)methanol (TCPMOH) were
      measured in the blubber of California sea lions (Zalophus californianus)
      collected in 2000. DDTs were the most predominant contaminants, followed by PCBs,
      chlordanes, TCPMe, HCHs, TCPMOH, dieldrin, and heptachlor epoxide. Concentrations
      of PCBs and DDTs varied from a few microg/g to several hundreds of microg/g on a
      lipid weight basis. Concentrations of DDTs have declined by an order of magnitude
      over the last three decades in California sea lions; nevertheless, the measured
      concentrations of PCBs and DDTs in California sea lions are still some of the
      highest values reported for marine mammals in recent years. Concentrations of
      organochlorines were highly correlated with one another. Concentrations of PCBs
      and DDTs in the blubber of gray whale, humpback whale, northern elephant seal,
      and harbor seal, and in the adipose fat of sea otter, were lower than the levels
      found in California sea lions, and were in the range of a few to several microg/g
      on a lipid weight basis.

PMID- 15261407
TI  - Mechanisms of lead, copper, and zinc retention by phosphate rock.
AB  - The solid-liquid interface reaction between phosphate rock (PR) and metals (Pb,
      Cu, and Zn) was studied. Phosphate rock has the highest affinity for Pb, followed
      by Cu and Zn, with sorption capacities of 138, 114, and 83.2 mmol/kg PR,
      respectively. In the Pb-Cu-Zn ternary system, competitive metal sorption occurred
      with sorption capacity reduction of 15.2%, 48.3%, and 75.6% for Pb, Cu, and Zn,
      respectively compared to the mono-metal systems. A fractional factorial design
      showed the interfering effect in the order of Pb>Cu>Zn. Desorption of Cu and Zn
      was sensitive to pH change, increasing with pH decline, whereas Pb desorption was
      decreased with a strongly acidic TCLP extracting solution (pH = 2.93). The
      greatest stability of Pb retention by PR can be attributed to the formation of
      insoluble fluoropyromorphite [Pb(10)(PO(4))(6)F(2)], which was primarily
      responsible for Pb immobilization (up to 78.3%), with less contribution from the
      surface adsorption or complexation (21.7%), compared to 74.5% for Cu and 95.7%
      for Zn. Solution pH reduction during metal retention and flow calorimetry
      analysis both supported the hypothesis of retention of Pb, Cu, and Zn by surface
      adsorption or complexation. Flow calorimetry indicated that Pb and Cu adsorption
      onto PR was exothermic, while Zn sorption was endothermic. Our research
      demonstrated that PR can effectively remove Pb from solutions, even in the
      presence of other heavy metals (e.g. Cu, Zn).

PMID- 15261408
TI  - Metal binding by humic acids isolated from water hyacinth plants (Eichhornia
      crassipes [Mart.] Solm-Laubach: Pontedericeae) in the Nile Delta, Egypt.
AB  - Humic acids (HAs) are animal and plant decay products that confer water
      retention, metal and organic solute binding functions and texture/workability in
      soils. HAs assist plant nutrition with minimal run-off pollution. Recent
      isolation of HAs from several live plants prompted us to investigate the HA
      content of the water hyacinth (Eichhornia crassipes [Mart.] Solm-Laubach:
      Pontedericeae), a delicately flowered plant from Amazonian South America that has
      invaded temperate lakes, rivers and waterways with devastating economic effects.
      Hyacinth thrives in nutrient-rich and polluted waters. It has a high affinity for
      metals and is used for phytoremediation. In this work, HAs isolated from the
      leaves, stems and roots of live water hyacinth plants from the Nile Delta, Egypt
      were identified by chemical and spectral analysis and by comparison with
      authentic soil and plant derived HAs. Similar carbohydrate and amino acid
      distributions and tight metal binding capacities of the HAs and their respective
      plant components suggest that the presence of HAs in plants is related to their
      metal binding properties.

PMID- 15261409
TI  - Effect of zinc fertilization on cadmium toxicity in durum and bread wheat grown
      in zinc-deficient soil.
AB  - The effect of increasing application of zinc (Zn) and cadmium (Cd) on shoot dry
      weight and shoot concentrations of Zn and Cd was studied in bread and durum wheat
      cultivars. Plants were grown in severely Zn-deficient calcareous soil treated
      with increasing Zn (0 and 10 mg kg(-1) soil) and Cd (0, 10 and 25 mg kg(-1) soil)
      and harvested after 35 and 65 days of growth under greenhouse conditions. Growing
      plants without Zn fertilization caused severe depression in shoot growth,
      especially in durum wheat and at high Cd treatment. Cadmium treatments resulted
      in rapid development of necrotic patches on the base and sheath parts of the
      oldest leaves of both wheat cultivars, but symptoms were more severe in durum
      wheat and under Zn deficiency. Decreases in shoot dry weight from increasing Cd
      application were more severe in Zn-deficient plants. Severity of Cd toxicity
      symptoms in durum and bread wheat at different Zn treatments did not show any
      relation to the Cd concentrations in shoot. Increasing Cd application to Zn
      deficient plants tended to decrease Zn concentrations in Zn-deficient plants,
      whereas in plants with adequate Zn, concentrations of Zn were either not affected
      or increased by Cd. The results show that durum wheat was more sensitive to both
      Zn deficiency and Cd toxicity as compared to bread wheat. Cadmium toxicity in the
      shoot was alleviated by Zn treatment, but this was not accompanied by a
      corresponding decrease in shoot concentrations of Cd. Our results are compatible
      with the hypothesis that Zn protects plants from Cd toxicity by improving plant
      defense against Cd-induced oxidative stress and by competing with Cd for binding
      to critical cell constituents such as enzymes and membrane protein and lipids.

PMID- 15261410
TI  - Factors affecting the concentrations of lead in British wheat and barley grain.
AB  - The entry of Pb into the food chain is of concern as it can cause chronic health
      problems. The concentration of Pb was determined in cereal grain samples
      collected representatively from British Cereal Quality Surveys in 1982 and 1998
      (n = 176, 250 and 233 for wheat collected in 1982 and 1998, and barley in 1998,
      respectively). In addition, paired soil and grain samples were collected from 377
      sites harvested across Britain in 1998-2000. Wheat grain Pb ranged from below the
      analytical detection limit (0.02 mg kg(-1) dry weight, DW) to 1.63 mg kg(-1) DW,
      and barley grain Pb from <0.02 to 0.48 mg kg(-1) DW. The vast majority of samples
      (>99% for both wheat and barley, excluding Scottish barley samples collected in
      2000) were well below the newly introduced EU limit for the maximum permissible
      concentration of Pb in cereals (0.2 mg kg(-1) fresh weight, equivalent to 0.235
      mg kg(-1) DW). There was a significant reduction in wheat grain Pb in the 1998
      survey compared with the 1982 survey. However, 40 barley samples collected from
      Scotland in 2000 in the paired soil and crop survey showed anomalously high
      concentrations of Pb, with 10 samples exceeding the EU limit. Washing experiments
      demonstrated that surface contamination, introduced during grain harvest and/or
      storage, was the main reason for the high concentrations in these samples. In the
      paired soil and crop surveys, there were no significant correlations between
      grain Pb concentrations with total soil Pb and other soil properties, indicating
      low bioavailability of Pb in the soils and limited uptake and transport of Pb to
      grain. The Pb in cereal grain is likely to originate mainly from atmospheric
      deposition and other routes of surface contamination during harvest and storage.

PMID- 15261411
TI  - Re-evaluation of metal bioaccumulation and chronic toxicity in Hyalella azteca
      using saturation curves and the biotic ligand model.
AB  - Bioaccumulation by Hyalella of all metals studied so far in our laboratory was re
      evaluated to determine if the data could be explained satisfactorily using
      saturation models. Saturation kinetics are predicted by the biotic ligand model
      (BLM), now widely used in modelling acute toxicity, and are a pre-requisite if
      the BLM is to be applied to chronic toxicity. Saturation models provided a good
      fit to all the data. Since these are mechanistically based, they provide
      additional insights into metal accumulation mechanisms not immediately apparent
      when using allometric models. For example, maximum Cd accumulation is dependent
      on the hardness of the water to which Hyalella are acclimated. The BLM may need
      to be modified when applied to chronic toxicity. Use of saturation models for
      bioaccumulation, however, also necessitates the need for using saturation models
      for dose-response relationships in order to produce unambiguous estimates of LC50
      values based on water and body concentrations. This affects predictions of
      toxicity at very low metal concentrations and results in lower predicted toxicity
      of mixtures when many metals are present at low concentrations.

PMID- 15261412
TI  - Clonal variation in heavy metal accumulation and biomass production in a poplar
      coppice culture: I. Seasonal variation in leaf, wood and bark concentrations.
AB  - The use of plants to decontaminate soils polluted by heavy metals has received
      considerable attention in recent years as a low-cost technique. Poplars (Populus
      spp.) can accumulate relatively high levels of certain metals, and have the added
      advantage of producing biomass that can be used for energy production. A short
      rotation coppice culture with 13 poplar clones was established on a former waste
      disposal site, which was moderately polluted with heavy metals. Total content of
      metals in leaves, wood and bark were determined in August and October/November.
      Significant clonal differences in accumulation were found for most metals,
      although clones with the highest concentration of all metals were not found.
      Cadmium, zinc and aluminium were most efficiently taken up. The lowest
      concentration was found in wood; the highest concentrations were generally found
      in senescing leaves, making removal and treatment of fallen leaves necessary.

PMID- 15261413
TI  - Arsenic and heavy metal mobility in iron oxide-amended contaminated soils as
      evaluated by short- and long-term leaching tests.
AB  - Several iron-bearing additives were evaluated for their effectiveness in the
      attenuation of arsenic (As) in various contaminated soils. These were selected
      for their known or potential ability to adsorb As anions, thus changing the
      speciation of As in a soil system. Three soils with different sources of As
      contamination were investigated (canal dredgings, coal fly ash deposits, and low
      level alkali waste). The amendments used were goethite (alpha-FeOOH), iron grit,
      iron (II) and (III) sulphates (plus lime), and lime, applied to the soils at a
      rate of 1% w/w. A series of leachate extraction tests (UKEA, ASTM and modified
      Dutch column leaching test) were conducted on the equilibrated amended soils.
      These were used to firstly evaluate the potential of the amendments as
      immobilising agents, and secondly to compare the short- and long-term durability
      of their effects. Column tests demonstrated the efficiency of iron oxides over
      the longer time scale; these treatments significantly reduced concentrations of
      arsenic in leachates from all treated soils. Amended soils were also observed to
      contain higher levels of lead (Pb) and cadmium (Cd) in their leachates,
      signifying that certain Fe-oxides potentially increased heavy metal mobility in
      treated soils. The conclusions were that whilst Fe-oxides may be used as
      effective in situ amendments to attenuate As in soils, their effects on other
      trace elements, such as Pb and Cd, require careful consideration.

PMID- 15261414
TI  - Prediction of phenanthrene uptake by plants with a partition-limited model.
AB  - The performance of a partition-limited model on prediction of phenanthrene uptake
      by a wide variety of plant species was evaluated using a greenhouse study. The
      model predictions of root or shoot concentrations for tested plant species were
      all within an order of magnitude of the observed values. Modeled root
      concentrations appeared to be more accurate than modeled shoot concentrations.
      The differences of simulated and experimented concentrations of phenanthrene in
      roots and shoots of three representative plant species, including ryegrass,
      flowering Chinese cabbage, and three-colored amaranth, were less than 81% for
      roots and 103% for shoots. Results are promising in that the alpha(pt) values of
      the partition-limited model for root uptake of phenanthrene correlate well with
      root lipid contents. Additionally, a significantly positive correlation is also
      observed between root concentration factors (RCFs, defined as the ratio of
      contaminant concentrations in root and in soil on a dry weight basis) of
      phenanthrene and root lipid contents. Results from this study suggest that the
      partition-limited model may have potential applications for predicting the plant
      PAH concentration in contaminated sites.

PMID- 15261415
TI  - Seasonal variation in the composition and concentration of butyltin compounds in
      marine fish of Taiwan.
AB  - For the first time, strong evidence is presented to demonstrate that the
      accumulations of butyltin compounds (BTs) exhibit seasonal variations with
      respect to their compositions and concentrations in marine fishes. Measurements
      were made on the benthic ponyfish Leiogenathus splendens and lizardfish
      Trachinocephalus myops inhabiting the west coast of Taiwan. In the whole body
      samples of the ponyfish, BT concentrations ranged from 236 to 2501 ng/g wet wt,
      with those in winter considerably higher than in the other seasons (p < 0.05 ).
      In a similar vein, proportions of mono- (MBT), di- (DBT) and tributyltin (TBT)
      differed significantly (p < 0.001) depending upon the season, with TBT (75 and
      50%) dominant in winter and spring and DBT (37 and 57%) and MBT (42 and 24%)
      dominant in summer and autumn, respectively. In the lizardfish, the
      concentrations of BTs were one to two orders of magnitude higher in the liver
      than in the muscle, i.e. 3058-11,473 vs. 36-159 ng/g wet wt, respectively.
      Concentrations of MBT, DBT and TBT in the muscle ranged, respectively, from 5 to
      14, 8 to 35 and 23 to 110 ng/g wet wt, with the major compound being TBT (57-69%)
      in all seasons. However, in the liver, DBT concentrations, ranging from 992 to
      7797 ng/g wet wt, differed seasonally with a descending order of
      autumn>summer>spring (p < 0.05). Meanwhile, TBT (41%) was predominant in spring,
      whereas DBT (50 and 68%) was most heavily concentrated in summer and autumn (p <
      0.001). Seasonally mediated physiological changes, such as dilution due to growth
      and metabolic compensation, may play important roles in forming different BT
      accumulation patterns among seasons and organisms.

PMID- 15261416
TI  - 137Cs contamination in tea and yerba mate in South America.
AB  - Gamma-ray spectra from more than 50 samples of food products available in stores
      of Buenos Aires city were measured using a germanium detector. Activity
      concentrations of 137Cs up to 10 Bq/kg were found in tea and yerba mate
      manufactured in Apostoles, Argentina. Further measurements of tea leaves, yerba
      mate leaves and soils, all coming from a cultivated area in that region, also
      show the presence of 137Cs contamination. The results suggest that the area was
      fertilized with a product that originated in a region affected by the fallout
      from the Chernobyl nuclear plant accident.

PMID- 15261417
TI  - Radon variations during treatment in thermal spas of Lesvos Island (Greece).
AB  - The aim of this paper was to study the variations of radon and daughter nuclei
      during treatment in the thermal spas of Lesvos Island (Greece). For this purpose,
      in the thermal spas of Lesvos we have measured the radon concentrations of
      thermal waters, as well as indoor radon, daughter and coarse particle (>500 nm)
      concentrations. Various instruments and procedures were employed for
      measurements. Radon concentrations of thermal waters were found to lie in the
      range 10 Bq l(-1) and 304 Bq l(-1). Concentration peaks both for radon, radon
      daughter and coarse particle, were found to appear during filling of baths in the
      treatment process. The doses delivered to the bathers during treatment were in
      the range of 0.00670-0.1279 mSv per year, while the doses delivered to personnel
      were below 20 mSv per year.

PMID- 15261418
TI  - Determination of depleted uranium in environmental samples by gamma-spectroscopic
      techniques.
AB  - The military use of depleted uranium initiated the need for an efficient and
      reliable method to detect and quantify DU contamination in environmental samples.
      This paper presents such a method, based on the gamma spectroscopic determination
      of 238U and 235U. The main advantage of this method is that it allows for a
      direct determination of the U isotope ratio, while requiring little sample
      preparation and being significantly less labor intensive than methods requiring
      radiochemical treatment. Furthermore, the fact that the sample preparation is not
      destructive greatly simplifies control of the quality of measurements. Low energy
      photons are utilized, using Ge detectors efficient in the low energy region and
      applying appropriate corrections for self-absorption. Uranium-235 in particular
      is determined directly from its 185.72 keV photons, after analyzing the 235U
      226Ra multiplet. The method presented is applied to soil samples originating from
      two different target sites, in Southern Yugoslavia and Montenegro. The analysis
      results are discussed in relation to the natural radioactivity content of the
      soil at the sampling sites. A mapping algorithm is applied to examine the spatial
      variability of the DU contamination.

PMID- 15261419
TI  - Inverse dependency of particle residence times in ponds to the concentration of
      phosphate, the limiting nutrient.
AB  - 234Th, a commonly used short-lived particle-reactive tracer in marine systems,
      was measured in three different holding pond series at the Rocky Flats
      Environmental Technology Site (RFETS), Colorado, along with its parent nuclide
      238U, to determine steady-state residence times of particle-reactive actinides
      such as Pu, and of particles. Series B ponds, which received industrial effluent
      that includes ortho-phosphate (PO4) and actinides, differed from series A and C
      ponds, which did not. This difference was also evident in the calculated particle
      residence times, which were <1 day for the ponds B4 and B5, where PO4
      concentrations were higher (1.4 and 1.8 mg/l), and 3 and 3.4 days for ponds A3
      and C2, respectively, where ortho-phosphate concentrations were lower (<0.1
      mg/l). Particle residence times thus showed an inverse relationship with the
      concentration of ortho-phosphate, the limiting nutrient in fresh water systems.
      The same relationship to the concentration of ortho-phosphate or any of the other
      nutrient elements was not evident for the residence times of dissolved 234Th,
      which ranged between 0.1 and 2 days. This can be attributed to higher
      concentrations of dissolved and particulate ligands with greater binding
      potential for actinides such as four-valent Th and Pu in ponds with higher ortho
      phosphate concentrations. Regardless of actual ortho-phosphate concentration,
      however, at water residence (holding) times of 1 month in these ponds, particles
      and associated actinides would be expected to be completely removed from the pond
      water to sediments.

PMID- 15261420
TI  - Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South
      America.
AB  - Groundwater samples were analysed for 222Rn, 226Ra, and 228Ra in Guarani aquifer
      spreading around 1 million km2 within four countries in South America, and it was
      found that their activity concentrations are lognormally distributed. Population
      weighted average activity concentration for these radionuclides allowed to
      estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the
      total effective dose or two times higher (0.21 mSv/year) than this limit,
      depending on the choice of the dose conversion factor. Such calculation adds
      useful information for the appropriate management of this transboundary aquifer
      that is socially and economically very important to about 15 million inhabitants
      living in Brazil, Argentina, Uruguay and Paraguay.

PMID- 15261421
TI  - Systematic radium survey in spring waters of Slovenia.
AB  - Radium (226Ra) concentration in 115 Slovenian springs ranged from 7.8 to 43.1 Bq
      m(-3), well below the current Slovenian limit of 1000 Bq m(-3) for drinking
      water. It showed two distributions, one grouped at around 24 Bq m(-3) and the
      other at around 37 Bq m(-3). Contrary to expectation, the level of radium does
      not always relate to the aquifer type. Only at aquifers and springs composed of
      acid, intermediate and basic igneous and metamorphic rocks, did radium
      concentration exceed 36 Bq m(-3) and was below this value at the majority of
      aquifers composed of carbonate and other sedimentary rocks.

PMID- 15261422
TI  - A dynamic compartment model for assessing the transfer of radionuclide deposited
      onto flooded rice-fields.
AB  - A dynamic compartment model has been studied to estimate the transfer of
      radionuclides deposited onto flooded rice-fields after an accidental release. In
      the model, a surface water compartment and a direct shoot-base absorption from
      the surface water to the rice-plant, which are major features discriminating the
      present model from the existing model, has been introduced to account for the
      flooded condition of rice-fields. The model has been applied to the deposition
      experiments of 137Cs on rice-fields that were performed at three different times
      to simulate the deposition before transplanting (May 2) and during the growth of
      the rice (June 1 and August 12), respectively. In the case of the deposition of
      May 2, the root-uptake is the most predominant process for transferring 137Cs to
      the rice-body and grain. When the radionuclide is applied just after
      transplanting (June 1), the activity of the body is controlled by the shoot-base
      absorption and the activity of the grain by the root-uptake. The deposition just
      before ear-emergence (August 12) shows that the shoot-base absorption contributes
      entirely to the increase of both the activities of the body and grain. The model
      prediction agrees within one or two factors with the experimental results
      obtained for a respective deposition experiment.

PMID- 15261423
TI  - Environmental radon studies using solid state nuclear track detectors.
AB  - The results of radon activity recorded in 70 dwellings of Nurpur area, Kangra
      district, Himachal Pradesh, India are reported. LR-115 Type 2 films in the bare
      mode were exposed for four seasons of three months each covering a period of one
      year for the measurement of indoor radon levels. The calibration constant of
      0.020 tracks cm(-2) d(-1) per Bq m(-3) has been used to express radon activity in
      Bq m(-3). The annual average indoor radon concentrations in 17 different villages
      of the area are found to vary from 168+/-46 to 429+/-71. Most of the indoor radon
      values lie in the range of action levels (200-600 Bq m(-3)) recommended by
      International Commission on Radiological Protection.

PMID- 15261424
TI  - Second Heidelberg Thoracic Oncology Symposium on the Diagnosis and Treatment of
      Pleural Mesothelioma--introduction.

PMID- 15261425
TI  - Asbestos and mesothelioma in South Africa.
AB  - Asbestos has been used by man since 4000 before the Christian era (BCE) in many
      different parts of the world and for a wide range of functions. Blue asbestos
      (crocidolite) was first discovered in South Africa in 1805 and within a few years
      was being mined there extensively. Mining reached its peak in 1977 with >380,000
      tons being exported and 20,000 miners employed in the industry. South Africa also
      has large deposits of white asbestos (chrysotile) and brown asbestos (amosite)
      both of which have been mined extensively. At the turn of the 20th century, it
      was noted that those working with asbestos suffered lung disease and in 1960, the
      link between asbestosis and mesothelioma was established in the Kimberley area of
      South Africa. Further studies in the 1970s and 1980s showed an alarming incidence
      of mesothelioma based on pathology reports. The majority of the reported
      mesothelioma cases result from exposure to asbestos in its many uses in secondary
      industry although incidence of the condition among miners is also significant. A
      high proportion of mesothelioma in patients in South Africa is attributed to
      environmental origin with a high incidence of women and children affected.

PMID- 15261426
TI  - The epidemiology of asbestos-related diseases.
AB  - Asbestos has been recognised as a potential health hazard since the 1940s. Of the
      two major species of asbestos; white asbestos (chrysotile) and blue asbestos
      (crocidolite), both of which are hazardous. The workers at extraction facilities
      are at the greatest risk of exposure to asbestos and, therefore, the development
      of asbestos-related diseases, commonly mesothelioma. However, other individuals
      at a high risk of exposure include asbestos-cement workers, insulation workers
      and ship-yard workers. Environmental exposure to asbestos can occur as a result
      of living in areas either characterised by natural outcrops of asbestos or
      asbestos-related materials, or those close to asbestos-producing or -using
      plants. Unfortunately, man-made fibre alternatives to asbestos, such as rock and
      slag-wool and glass wool, have also been shown to have a detrimental effect on
      human health. A characteristic of mesothelioma is that there is a long latency
      period (20-30 years) before the signs and symptoms of the disease become
      apparent. In addition, diagnosis of the disease can be difficult. The use of
      biological markers, such as tissue polypeptide antigen, may play a useful role in
      the early detection of the disease in individuals at risk.

PMID- 15261427
TI  - Malignant pleural mesothelioma in Turkey, 2000-2002.
AB  - Both asbestos and erionite related malignant pleural mesothelioma (MPM) is a
      serious health problem in Turkey. Erionite has a higher potency in the lung than
      asbestos and familial clustering of malignant mesothelioma suggests a genetic
      predisposition to this cancer among affected individuals. Neither Simian virus 40
      (SV40) nor human herpes virus 8 (HHV-8) are co-factors in the pathenogenesis of
      environmentally induced mesothelioma. A survival advantage has been demonstrated
      in patients with asbestos-induced mesothelioma compared with erionite-induced
      mesothelioma. This together with the proliferation index (PI) can be used as an
      independent prognostic factor for patients with malignant pleural mesothelioma.
      It is envisaged that the application of these prognostic approaches together with
      the new TNM staging system will allow investigations to be more precisely carried
      out and evaluated.

PMID- 15261428
TI  - Epidemiology of malignant mesothelioma in Australia.
AB  - In Australia, consumption of asbestos peaked in about 1975 at around 70,000t per
      year--the majority being used for asbestos cement manufacture. Chrysotile,
      amphibole and crocidolite have all been mined in Australia and employment records
      from the single company which mined most of the crocidolite deposits at Wittenoom
      have formed the basis of an ongoing cohort mortality study of the workforce.

PMID- 15261429
TI  - Epidemiology of pleural mesothelioma in Italy.
AB  - The incidence of malignant mesothelioma (MM) in Italy is increasing and is
      assumed to be a consequence of high levels of asbestos exposure. Establishment of
      the National Mesothelioma Registry (ReNaM) and the co-operation of five regional
      centers has allowed the estimation of the incidence of malignant mesothelioma in
      major parts of Italy and the definition of exposure to asbestos.

PMID- 15261430
TI  - Pathological anatomy and molecular pathology.
AB  - The incidence of malignant mesotheliomas in Germany has increased since about the
      mid 1980s, and a further increase is expected until about 2020 due to the peak in
      asbestos processing in Germany between 1965 and 1980. About 90% of the
      mesotheliomas recorded in the files of the German Mesothelioma Registry in Bochum
      are asbestos-related and therefore possibly due to an occupational exposure. In
      2003, 717 mesotheliomas were newly diagnosed at the German Mesothelioma Registry.
      Mesotheliomas are very heterogeneous in terms of histological appearances and of
      prognosis. At present, the diagnostic gold standard is conventional histology in
      combination with additional immunohistochemical analysis. We were not able to
      confirm a promising report that described telomerase reverse transcriptase
      catalytic subunit (TERT) for the differentiation between reactive and neoplastic
      mesothelial lesions, which can be extremely difficult. DNA cytometric analysis
      may also help differentiate between reactive and neoplastic mesothelial lesions.
      There are some characteristic patterns of chromosomal imbalances as detectable by
      comparative genomic hybridization (CGH), but at present, specific chromosomal or
      genetic defects that give rise to a mesothelioma are not known. A reliable
      pathological diagnosis is the basis for therapeutic, prognostic, and medicolegal
      consequences. In general, it can be achieved by thoracoscopic inspection with
      specifically directed biopsy. Furthermore, a description of the peculiarities of
      each mesothelioma by the pathologist might be the key to a more individual
      therapy in the future.

PMID- 15261431
TI  - Pathology of malignant mesothelioma.
AB  - The diagnosis of malignant mesothelioma relies firstly on the identification of
      the mesothelial nature of the neoplastic cell and secondly on the demonstration
      of the invasive properties of the proliferation. The latter aspect cannot be
      achieved by studying cellular material yet, in the right clinical setting, it is
      often possible to make a presumptive diagnosis of malignant mesothelioma based on
      exudates. Differentiation between mesothelial hyperplasia and metastatic
      adenocarcinoma by cytological examination alone is unreliable, so further
      evidence can be gathered from techniques such as histopathology, histochemistry
      and electron microscopy. Immunohistochemistry aims to confirm the mesothelial
      nature of the neoplastic cells while ruling out metastatic lesions. At present
      there is no single reliable marker for neoplastic mesothelioma, although evidence
      has been presented on a large variety of gene products. In an attempt to
      differentiate between hyperplastic mesothelium and malignant mesothelioma, Dhaene
      has been able to show that over 90% of malignant mesotheliomas show telomerase
      activity and express telomerase subunits.

PMID- 15261432
TI  - Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and
      its diagnostic and biological relevance.
AB  - Cadherins and their associated cytoplasmic proteins, catenins, are critical to
      the maintenance of normal tissue integrity and the suppression of cancer
      invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined
      and the role of the cadherin-catenin system in the pathogenesis of MM remains to
      be determined. By means of Western blot analysis and immunohistochemistry the
      expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-,
      beta- and gamma-catenins was studied in nine human MM cell lines and five human
      mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin
      and alpha- and beta-catenins. All but one MM cell line were N-cadherin-positive
      and all of them were also positive for alpha- and beta-catenins. E-cadherin was
      found in six (66.7%) and gamma-catenin in seven (77.8%) MM cell lines. Five of
      these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was
      also P-cadherin-positive. Double immunofluorescence staining revealed the plasma
      membrane co-localisation of both cadherin types in MM cell lines that co
      expressed E- and N-cadherin or E- and P-cadherin, respectively.
      Immunoprecipitation showed complexes of beta-catenin with both cadherin types
      when co-expressed. The results point to upregulation of E-cadherin and gamma
      catenin in most MM cases and demonstrate that cadherin expression is more
      heterogeneous and less mutually exclusive in MM compared with the mesothelium,
      although the biological significance of this finding remains unclear.

PMID- 15261433
TI  - Clinico-pathological and biological prognostic factors in pleural malignant
      mesothelioma.
AB  - In the UK mortality from malignant mesothelioma (MM) is likely to more than
      double over the next 20 years and despite advances in surgery, chemotherapy and
      radiation treatment the overall prognosis for patients remains poor. A number of
      scoring systems based on assessment of clinicopathological features of patients
      with the disease have been developed but the search continues for further
      prognostic indicators. Angiogenesis, tumour necrosis (TN), epidermal growth
      factor receptor (EGFR) expression, cyclooxygenase-2 (COX-2) and matrix
      metalloproteinases (MMPs) have been linked with poor prognosis in some types of
      solid tumour and their relevance as prognostic factors in malignant mesothelioma
      is examined in this paper.

PMID- 15261434
TI  - Prognostic factors in malignant mesothelioma.
AB  - Many prognostic factors have been described in malignant mesothelioma, but only a
      limited number has been validated by prospective, confirmatory studies. These
      include performance status, histology, weight loss and leucocyte count. Their
      value as predictors of patient survival in malignant mesothelioma is limited, as
      is their role in current clinical practice. At this moment their main importance
      is their application in clinical studies, which allows a better delineation of
      the patient group to which the study results can be applied to and a more
      accurate comparison between different studies. The biological prognostic factors
      need confirmation by larger prospective trials and should be analysed with
      respect to the existing prognostic factors. In the future, their use might not be
      limited to the prediction of the patient survival but direct the development of
      new therapies and extend to the molecular prediction of tumour response.

PMID- 15261435
TI  - Staging and response to therapy of malignant pleural mesothelioma.
AB  - Earlier staging systems tended to concentrate on advanced malignant pleural
      mesothelioma (MPM) and considerable variation arose among the different systems.
      This was addressed in 1997 when the International Mesothelioma Interest Group
      (IMIG) staging system was approved. This is not a perfect system as many of the
      distinctions it makes cannot be identified by current computed tomography (CT)
      and magnetic resonance imaging (MRI) scanning. However presurgical staging using
      CT and MRI can be useful in delineating the extent and volume of disease and in
      detecting unexpected advanced disease as well as alerting clinicians to the
      possibility of early stage malignant pleural mesothelioma. Patients response to
      therapy can be measured using the response evaluation criteria in solid tumors
      (RECIST) criteria involving multiple measurements of a single diameter of tumour
      thickness.

PMID- 15261436
TI  - Diagnosis and staging of mesothelioma transthoracic ultrasound.
AB  - Various techniques are used for diagnosing mesothelioma including clinical
      investigation, transthoracic ultrasound, X-ray, computed tomography (CT),
      sonographic support puncture and thorascoscopy with biopsy. Whereas ultrasound
      examination of a normal lung is of limited value, it can be very useful in
      identifying pleural pathological processes. The presence of pleural effusion can
      substantially enhance the usefulness of ultrasound investigations: the liquid of
      the pleural effusion acts as an acoustic window and can enable the detection of
      intrapleural and intrapulmonal processes. Highly soluble transducers can be used
      to visualise pathological findings at the chest wall, enabling the recognition of
      pleural effusions and the diagnosis of pleural thickening, tumour tissue and
      abscesses. Further evidence for diagnosis can be obtained with ultrasound-guided
      puncture, using one of three techniques: sonographic supported puncture,
      sonographic-guided puncture without puncture assistance, and sonographic-guided
      puncture with puncture assistance. Complications such as bleeding, infection and
      local tumour cell propagation can arise.

PMID- 15261437
TI  - The use of magnetic resonance imaging in malignant mesothelioma.
AB  - Magnetic resonance imaging (MRI) is not routinely used in investigations for
      patients with suspected malignant pleural mesothelioma but it can be a useful
      tool in some instances--particularly predicting malignancy in patients with
      asbestos exposure; differentiating between metastatic pleural disease and
      malignant pleural mesothelioma (MPM); assessing patients for radical surgery and
      post treatment evaluation of patients.

PMID- 15261438
TI  - Positron emission tomography in the diagnosis of mesothelioma.
AB  - The increasing incidence of malignant pleural mesothelioma has led to the
      development of new treatment strategies and a need for new diagnostic techniques
      to identify the extent of the disease at an early stage and to evaluate
      treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) are
      helpful in identifying the location and extent of the involved areas but cannot
      always differentiate between benign and malignant processes. Fluorodeoxyglucose
      (FDG)-positron emission tomography (PET) imaging, which in oncology, is based on
      changes in metabolic pathways of glucose, has been shown in a number of studies
      to differentiate malign and benign lesions in patients with asbestos exposure.
      FDG-PET images were also found to provide excellent delineation of the active
      tumour sites. Further evaluations of this technique included a combined
      experimental/clinical study to investigate the difference in rates of FDG uptake
      between malignant and inflammatory cells and processes.

PMID- 15261439
TI  - Asbestos: a clear and present danger--a UK perspective.
AB  - The hazardous nature of asbestos has been recognised for over a hundred years
      yet, despite legislation to protect and compensate workers, the battle for
      adequate compensation continues.

PMID- 15261440
TI  - Malignant mesothelioma--British surgical strategies.
AB  - With the incidence of mesothelioma in the United Kingdom (UK) expected to attain
      epidemic proportions over the next 20 years, prospective randomised evaluation of
      the role of surgery in the treatment of mesothelioma is required so that
      appropriate resource planning can be made. Possible prospective trials to
      evaluate the role of radical surgery are proposed together with the principles
      which must be conceded in the approach to radical surgery, patient selection,
      resectability, operability, treatment modalities, debulking surgery, chemotherapy
      and radiotherapy.

PMID- 15261441
TI  - Radiation therapy of mesothelioma: the Heidelberg experience and future aspects.
AB  - Pleural mesothelioma is a rare but fatal tumour. Numerous attempts to find
      effective treatment approaches have, in general, been disappointing. To date, the
      most promising treatment is surgery, or surgery in combination with radio and
      chemotherapy as a part of a multidisciplinary approach. Preliminary results from
      clinical trials evaluating intensity modulated radiotherapy are encouraging.
      Further randomised trials are proposed.

PMID- 15261442
TI  - Considerations for post-operative radiotherapy to the hemithorax following
      extrapleural pneumonectomy in malignant pleural mesothelioma.
AB  - With growing interest in evaluating extrapleural pneumonectomy (EPP) and post
      operative in selected patients with early stage malignant pleural mesothelioma,
      it is essential that clinical trials should be conducted using a clear and
      reproducible radiotherapy protocol. The considerations which have determined the
      policy of radiotherapy planning and treatment delivery for patients with
      mesothelioma in The Netherlands are given. As well as general considerations such
      as patient selection, target volume and critical organ delineation, a dose
      fractionation scheme, constraints relating to normal tissue, treatment planning,
      the type of external beam equipment, treatment verification and radiation
      toxicity and scoring are all taken into account.

PMID- 15261443
TI  - Chemotherapy for malignant pleural mesothelioma: past results and recent
      developments.
AB  - This review summarises results of previously conducted clinical trials and
      subsequently presents data arising from all phase II-III studies on chemotherapy
      for malignant pleural mesothelioma (MPM) published since the last relevant
      overview. While response rates exceeding 30% have barely been achieved with
      established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and
      their combinations appear somewhat more promising. This applies especially to the
      antimetabolites, and in particular to pemetrexed which produced response rates of
      up to 45% in combination with platinum compounds. Raltitrexed combined with
      oxaliplatin has also been shown to be effective, and gemcitabine--applied as a
      single agent or in combination with cisplatin--as well as vinorelbine appear to
      improve quality of life in patients presenting with MPM. Data can now be more
      precisely analysed by increasingly implemented randomised studies, applying a
      standardised staging system, and distinguishing prognostic groups. While
      chemotherapy for MPM remains a challenging task, important steps have clearly
      been made in the past years to combat this aggressive disease. Publication of
      results from a phase III trial of pemetrexed with cisplatin in a peer reviewed
      journal may soon establish a standard of care.

PMID- 15261444
TI  - The role of Alimta in the treatment of malignant pleural mesothelioma: an
      overview of preclinical and clinical trials.
AB  - Malignant pleural mesothelioma (MPM) is a rare tumor, but its annual incidence is
      rapidly increasing. While most patients have locally advanced disease at
      presentation, to date there is no proven standard chemotherapy for MPM that has
      shown to increase survival in randomized studies. Therefore, the development of
      new therapeutic agents is urgent for this disease. Alimta is a novel,
      multitargeted antifolate with activity as single agent in patients with MPM.
      Recently, a phase III trial showed that the combination of Alimta with cisplatin
      resulted in a significantly increased efficacy compared with cisplatin alone. In
      addition, vitamin supplementation reduced treatment associated toxicities with no
      apparent affect on activity. This review summarizes preclinical and clinical data
      to define the future role of Alimta in the treatment of patients with MPM.

PMID- 15261445
TI  - Moving beyond chemotherapy: novel cytostatic agents for malignant mesothelioma.
AB  - It is now known that vascular endothelial growth factor (VEGF) and platelet
      derived growth factor (PDGF) are autocrine growth factors in malignant
      mesothelioma; epidermal growth factor receptor (EGFR) is also highly
      overexpressed. Cytotoxic drugs that target these growth factors offer fresh
      potential for the treatment of mesothelioma. Clinical trials have recently been
      initiated to evaluate the anti-tumour activity of the VEGF inhibitors SU5416,
      bevacizumab and thalidomide. ZD1839 (Iressa, AstraZeneca), an inhibitor of EGFR
      tyrosine kinase, is also being evaluated. Two clinical trials are planned to
      evaluate the two PDGF inhibitors Gleevec (Imatinib mesylate, STI-571, Novartis
      Pharmaceuticals) and PTK787 (Novartis Pharmaceuticals).

PMID- 15261446
TI  - Malignant mesothelioma. Medical oncology: standards, new trends, trials--the
      French experience.
AB  - Clinical trials investigating new trends in the treatment of stage I and II
      malignant mesothelioma have shown both intra-pleural immunotherapy and systemic
      chemo-immunotherapy to be efficacious. Intra-pleural gamma-interferon (gamma-IFN)
      therapy was associated with tolerable toxicity and an overall response (ORR) rate
      of 19%, while treatment with intra-pleural recombinant interleukin-2 (IL-2) was
      more toxic, but yielded an ORR of 47% in phase I trial and 55% in a phase II
      study. The association of intravenous cisplatin and subcutaneous alpha-interferon
      (alpha-IFN) was also associated with an encouraging ORR of 40% and a median
      survival of 12 months. Treatment with cisplatin, alpha-IFN and mitomycin C was
      associated with moderate toxicity and an ORR of 21% and a median survival of 12
      months. The association of cisplatin, alpha-IFN and IL-2 was, however, extremely
      toxic and resulted in an ORR of 15%. The majority of patients responding to intra
      pleural immunotherapy and systemic chemo-immunotherapy had epithelial type
      mesothelioma. The most encouraging results obtained from trials investigating
      systemic chemotherapy were following treatment with cisplatin, 5-fluorouracil,
      mitomycin C and etoposide, where an ORR of 38% and an overall median survival
      rate of 16 months were achieved. Toxicity was mainly haematological and
      tolerable.

PMID- 15261447
TI  - Malignant mesothelioma--the UK experience.
AB  - In Britain it is estimated that the annual number of mesothelioma deaths will
      rise from approximately 1500 in the year 2000 to a peak of approximately 3000 in
      2020. A database on the natural history of mesothelioma has provided a baseline
      for a new trial at The Royal Marsden looking at early versus delayed chemotherapy
      in mesothelioma as a new approach to treatment. In the UK chemotherapy is usually
      in the form of MVP (mitomycin, vinblastine and cisplatin) or vinorelbine, and
      data have been collected from trials covering both regimens. There is now a
      national working group for mesothelioma (BMIG) and a proposal for a national
      trial is being taken forward, comparing chemotherapy with MVP or single agent
      vinorelbine in addition to active symptom control (ASC) with ASC alone. Novel
      agents are also being investigated and SRL172 has shown some benefits in
      combination with chemotherapy in the treatment of malignant mesothelioma.

PMID- 15261448
TI  - Effects of dietary methylmercury on juvenile Sacramento blackfish bioenergetics.
AB  - Although much is known about the biogeochemical cycling of mercury in the
      environment, relatively little is known about methylmercury (MeHg)
      bioaccumulation in fishes and how chronic sub-lethal exposures affect their
      functioning. Several species of fish in Clear Lake, California have high MeHg
      tissue levels, including Sacramento blackfish, Orthodon microlepidotus, a large
      native cyprinid that is fished commercially. We fed juvenile blackfish one of
      four diets containing MeHg (0.21 mg/kg control; 0.52 mg/kg low; 22.2 mg/kg
      medium; and 55.5 mg/kg high treatments) for 70 days. There were no statistical
      differences (P > 0.05) in food consumption among the treatment groups. By 35 days
      the high treatment group had a significantly depressed growth rate when compared
      to the control group (P < 0.05) and by 70 days both the medium and the high
      groups had significantly lower growth rates (P < 0.05). The high-dose group had a
      significantly (P < 0.05) lower specific growth rate (SGR) compared all other
      treatment groups at 35 days, although by 70 days these differences were not
      significant. The wet/dry muscle mass and muscle mass/total mass ratios, condition
      factor, and resting routine metabolic rates at both 35 and 70 days were
      statistically indistinguishable (P > 0.05) between treatment groups. All
      treatment groups assimilated the dietary MeHg into muscle tissue in a dose
      dependent fashion. Percent assimilation was significantly lower (P < 0.05) in the
      high-dose group compared to the low-dose group at 35 days, (control 53%, low-dose
      61%, medium-dose 50%, and high-dose 40%) but at 70 days assimilation was lower
      (35, 43, 42, and 32%, respectively) and statistically indistinguishable (P >
      0.05) among the treatment groups. Dietary MeHg concentrations and bioaccumulation
      rates were correlated (r2 = 0.98 at 35 days, 0.99 at 70 days). These results may
      contribute to construction of ecosystem mercury models and more informed natural
      resources management at Clear Lake.

PMID- 15261449
TI  - Characterization of a domoic acid binding site from Pacific razor clam.
AB  - The Pacific razor clam, Siliqua patula, is known to retain domoic acid, a water
      soluble glutamate receptor agonist produced by diatoms of the genus Pseudo
      nitzschia. The mechanism by which razor clams tolerate high levels of the toxin,
      domoic acid, in their tissues while still retaining normal nerve function is
      unknown. In our study, a domoic acid binding site was solubilized from razor clam
      siphon using a combination of Triton X-100 and digitonin. In a Scatchard analysis
      using [3H]kainic acid, the partially-purified membrane showed two distinct
      receptor sites, a high affinity, low capacity site with a KD (mean +/- S.E.) of
      28 +/- 9.4 nM and a maximal binding capacity of 12 +/- 3.8 pmol/mg protein and a
      low affinity, high capacity site with a mM affinity for radiolabeled kainic acid,
      the latter site which was lost upon solubilization. Competition experiments
      showed that the rank order potency for competitive ligands in displacing
      [3H]kainate binding from the membrane-bound receptors was quisqualate > ibotenate
      > iodowillardiine = AMPA = fluorowillardiine > domoate > kainate > L-glutamate.
      At high micromolar concentrations, NBQX, NMDA and ATPA showed little or no
      ability to displace [3H]kainate. In contrast, Scatchard analysis using
      [3H]glutamate showed linearity, indicating the presence of a single binding site
      with a KD and Bmax of 500 +/- 50 nM and 14 +/- 0.8 pmol/mg protein, respectively.
      These results suggest that razor clam siphon contains both a high and low
      affinity receptor site for kainic acid and may contain more than one subtype of
      glutamate receptor, thereby allowing the clam to function normally in a marine
      environment that often contains high concentrations of domoic acid.

PMID- 15261450
TI  - Impacts of carbamate pesticides on olfactory neurophysiology and cholinesterase
      activity in coho salmon (Oncorhynchus kisutch).
AB  - Many freshwater aquatic environments in the Pacific Northwest of North America
      contain neurotoxic pesticides, an issue of concern given the use of many of these
      habitats by Pacific salmon (Oncorhynchus sp.). Pesticides such as carbamates are
      known to affect fundamental physiological systems (such as the enzyme
      acetylcholinesterase (AChE)), and have been shown to affect salmonid olfactory
      mediated behaviors. A neurophysiological measure of olfactory function, the
      electro-olfactogram (EOG), was used in this study to examine the impacts of acute
      localized exposure to three carbamates (the insecticide carbofuran, the
      antisapstain IPBC, and the fungicide mancozeb) on olfactory function in the coho
      salmon (Oncorhynchus kisutch). We also examine the potential for these pesticides
      to alter AChE levels in the primary olfactory system and brain with brief
      exposures (30 min to only the olfactory rosette (OR)). In results, we find that
      the EOG in coho salmon is highly sensitive to brief localized exposures of two of
      these three carbamate pesticides. The effective nominal concentration required to
      cause a 50% reduction in EOG amplitude (EC50) for carbofuran was 10.4 microg/l
      and for IPBC was 1.28 microg/l. For mancozeb, the EC50 was higher at 2.05 mg/l.
      All three carbamates also affected AChE activity levels in the OR and brain (BR):
      carbofuran exposure at 200 microg/l significantly inhibited AChE activity in the
      OR, and both IPBC and mancozeb significantly increased AChE activity in BR at
      multiple concentrations with acute localized exposure. These carbamate effects
      highlight the sensitivity of salmon olfactory neurophysiology to pesticides
      acting not only potentially via AChE-inhibition, but also by other currently
      unknown modes of action.

PMID- 15261451
TI  - Gastrointestinal uptake and fate of cadmium in rainbow trout acclimated to
      sublethal dietary cadmium.
AB  - Adult rainbow trout were pre-exposed to a sublethal concentration of dietary Cd
      (500 mg/kg dry wt.) for 30 days to induce acclimation. A gastrointestinal dose of
      radiolabeled Cd (276 microg/kg wet wt.) was infused into the stomach of non
      acclimated and Cd-acclimated trout through a stomach catheter. Repetitive blood
      samples over 24 h and terminal tissue samples were taken to investigate the
      gastrointestinal uptake, plasma clearance kinetics, and tissue distribution of
      Cd. Only a small fraction of the infused dose (non-acclimated: 2.4%; Cd
      acclimated: 6.6%) was internalized across the gut wall, while most was bound in
      the gut tissues (10-24%) or remained in the lumen (16-33%) or lost from the fish
      (approximately 50%) over 24 h. Cadmium loading during pre-exposure produced a
      profound increase of total Cd in the blood plasma (approximately 28-fold) and red
      blood cells (RBC; approximately 20-fold). The plasma Cd-time profiles consisted
      of an apparent rising (uptake) phase and a declining (clearance) phase with a
      maximum value of uptake in 4 h, suggesting that uptake of gastrointestinally
      infused Cd was very rapid. Acclimation to dietary Cd did not affect plasma Cd
      clearance (approximately 0.5 ml/min), but enhanced new Cd levels in the plasma
      (but not in the RBC), and resulted in a longer half-life for plasma Cd. Tissue
      total and new Cd levels varied in different regions of the gastrointestinal
      tract, and overall levels in gut tissues were much greater than in non-gut
      tissues, reflecting the Cd exposure route. Dietary Cd, but not the infused Cd,
      greatly increased total Cd levels of all gut tissues in the order posterior
      intestine (640-fold) > cecae (180-fold) > mid-intestine (94-fold) > stomach (53
      fold) in Cd-acclimated fish relative to naive fish. Among non-gut tissues in the
      Cd-acclimated fish, the great increases of total Cd levels were observed in the
      liver (73-fold), kidney (39-fold), carcass (35-fold), and gills (30-fold). The
      results provide some clear conclusions that may be useful for environmental risk
      assessment of dietary Cd exposure in fish.

PMID- 15261452
TI  - Interference of cadmium and copper with the endocrine control of ovarian growth,
      in the estuarine crab Chasmagnathus granulata.
AB  - The effects of cadmium and copper on the hormonal control of ovarian growth were
      evaluated on the estuarine crab Chasmagnathus granulata, by means of both in vivo
      (14 days exposure) and in vitro (24 h) assays. For both kind of assays, heavy
      metal concentrations of 0 (control), 0.5 mg/L of cadmium or 0.1 mg/L of copper
      were used. No significant (P > 0.05) change of the gonadosomatic index was
      observed in the in vivo assays with intact females exposed to heavy metals, while
      eyestalk-ablated exposed females showed significantly (P < 0.05) lower
      gonadosomatic index values than their respective controls. This latter result led
      us to consider the possibility that the interfered with extra-eyestalk hormones.
      In this sense, no differences were noted between control and heavy metals-exposed
      groups after co-incubating ovary with thoracic ganglion (the source of the gonad
      stimulating hormone). However, when ovary was incubated with methyl farnesoate or
      17-hydroxyprogesterone, 3H-leucine incorporation was significantly lower in the
      heavy metals-exposed groups than in the controls, indicating a possible
      interference of cadmium and copper with the transduction pathway of those
      hormones. On the other hand, ovaries co-incubated in vitro with eyestalk tissue
      and exposed to either heavy metal showed significantly higher 3H-leucine
      incorporation than did the controls, suggesting an inhibitory effect of both
      heavy metals on the secretion of the gonad inhibiting hormone from the eyestalk
      tissue. Interference by copper and cadmium with the transduction mechanisms of
      gonad inhibiting hormone at the ovarian level does not appear to be a viable
      hypothesis, because the addition of eyestalk extracts to the incubation medium
      reversed the effect caused by each heavy metal. The results from the in vitro
      assays were in accordance with those obtained with the intact crabs in vivo.

PMID- 15261453
TI  - DDT in zebra mussels from Lake Maggiore (N. Italy): level of contamination and
      endocrine disruptions.
AB  - The DDT contamination of Lake Maggiore (Northern Italy) has been monitored since
      a serious pollution event occurred in 1996. To assess the environmental risk
      associated with this contamination, bioaccumulation data coupled with
      histopathological markers were evaluated on zebra mussel populations from two
      different contaminated sites from April 2001 to April 2002. Biomonitoring results
      showed high DDT pollution in 2001 because of a flood which transported DDTs still
      contained in the sediments of a polluted river to the lake. DDT concentrations
      reached values of 4-5 microg/g lipids, higher than those recorded in other
      industrialized countries but comparable to levels measured in developing ones. In
      the ovaries of the most highly polluted mussels, histological analyses showed a
      delay in oocyte maturation and a high incidence of pathological pictures mainly
      referable to oocyte degeneration and haemocytic infiltration. Moreover, despite
      the presence of mature sperms, in 2001 first male gamete release occurred about 2
      months later than in females. These results indicated a neuroendocrine
      interference of DDT on Dreissena polymorpha reproduction and also showed that
      these invertebrates can be successfully used to evaluate ecological implications
      due to exposure to endocrine disruptors in freshwater environments.

PMID- 15261454
TI  - Seasonal variations in the effect of zinc pyrithione and copper pyrithione on
      pelagic phytoplankton communities.
AB  - The relationship between environmental factors, community composition and the
      sensitivity of pelagic phytoplankton to the antifouling agents zinc pyrithione
      (ZPT) and copper pyrithione (CPT) was studied using phytoplankton communities
      collected from March until August 2001 in Roskilde fjord, Denmark. Sensitivity to
      ZPT and CPT was measured as EC50 values obtained from dose-response curves of
      photosynthesis to ZPT and CPT. EC50 for ZPT and CPT varied between 2 and 60 nM
      and 4 and 25 nM, respectively. Changes in sensitivity throughout the season were
      related to changes in phytoplankton community composition and density, and to
      nutrient levels. It was found that the variation in sensitivity of ZPT and CPT
      was related to the abundance of the groups Cryptophyceae, Bacillariophycaea and
      Dinophyceae when they were dominating the community. Furthermore, the sensitivity
      to ZPT was increased at low concentrations of phosphate per cell (<0.2
      nmol/cell). For CPT there was a negative correlation between toxicity and
      phosphate concentration in the water. Consequently, in aquatic environments where
      phytoplankton is phosphate limited the effect of ZPT and CPT may be enhanced.

PMID- 15261455
TI  - Structural characterization of the caprine major histocompatibility complex class
      II DQB1 (Cahi-DQB1) gene.
AB  - The major histocompatibility class II genes have been extensively characterized
      in sheep and cattle, whereas in goats the only class II genes that have been
      completely sequenced are DRA and DRB. Herewith, we report the complete coding
      sequence of the goat DQB1 gene. This gene has a single open reading frame of
      786bp, being organized in five exons and displaying 95-97% nucleotide identity
      with its bovine and ovine cDNA orthologous sequences. The structural features of
      the goat DQB1 molecule are well conserved with regard to its mammalian
      orthologues. Conserved glycosilation sites (beta19) and cysteine residues
      (beta15, beta79, beta117, beta173) forming disulfide bridges have been identified
      in the goat DQB1 molecule. The alignment of several Cahi-DQB1 exon 2 sequences
      has allowed to identify five different allelic variants Neighbor-joining
      phylogenetic analysis of caprine, ovine and bovine DQB sequences has allowed to
      ascertain that the five Cahi-DQB1 alleles we have found correspond to three
      different allelic lineages. We have identified fifteen polymorphic positions in
      the Cahi-DQB1 molecule, but only six of them are located in the peptide binding
      region. The high degree of conservation of these polymorphic sites located
      outside the peptide binding region in cattle and sheep suggests that they might
      play a functional role in antigen-presentation to CD4+ T cells.

PMID- 15261456
TI  - Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal
      cells.
AB  - Histone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and
      this is linked to formation of transcriptionally active chromatin in various
      cells. In this study, the effect of HDAC inhibitors (butyrate, trichostatin A
      (TSA)) on the expression of the cathelicidin LL-37 in colon, gastric and
      hepatocellular cells was investigated. METHODS: LL-37 expression was assessed in
      colon, gastric and hepatocellular cancer cells after treatment with HDAC
      inhibitors. In parallel, histone H4 and HMGN2, a non-histone protein, acetylation
      was evaluated. In addition, the intracellular signalling pathway MEK-ERK was
      explored. RESULTS: In contrast to normal colon epithelial cells, gastrointestinal
      cancer cells lacked LL-37 expression. LL-37 was induced following treatment with
      HDAC-inhibitors in all investigated cell lines. This induction was time-dependent
      in butyrate-treated cells while TSA exerted a transient effect. Induction of LL
      37 by butyrate was paralleled by acetylation of the histone H4 and the non
      histone HMGN2. Again, TSA resulted in transient acetylation. Furthermore,
      inhibition of MEK-ERK blocked HDAC inhibitor-induced LL-37 expression in colonic
      and gastric cells. CONCLUSIONS: We have previously shown that butyrate induces LL
      37 in colon epithelial cells. In the present study, we demonstrate that
      cathelicidin expression is modulated by HDAC-inhibitors in various
      gastrointestinal cells including gastric and hepatocellular cells. This is
      paralleled by changes in the acetylation of distinct core proteins suggesting a
      common regulatory mechanism of cathelicidin LL-37 regulation in these cells.

PMID- 15261457
TI  - Identification of a novel GC-rich binding protein that binds to an indispensable
      element for constitutive IRF-4 promoter activity in B cells.
AB  - Interferon regulatory factor-4 (IRF-4) is a lymphoid-specific transcription
      factor that plays crucial roles in the development and the functions of immune
      cells. B lymphocytes express IRF-4 constitutively. In this report, we
      investigated the transcriptional control of IRF-4 in B lymphocytes. Successive
      deletions of the IRF-4 promoter from -4799 revealed that the region between -51
      and -28 (5'-CGCCCGCCCCAGGCCCCGCCCCA-3') was required for the basal promoter
      activity. Mutations in the distal and proximal sites of this GC-rich sequence
      resulted in 62 and 81% reductions in the IRF-4 promoter activity, respectively.
      EMSA observations revealed the formation of a protein complex with the
      corresponding DNA, which was sensitive to mutations in the GC-rich sequences. UV
      photocrosslinking assays identified a novel 60 kDa protein with a similar
      sequence preference. The possible involvement of this factor in the regulation of
      IRF-4 gene expression is discussed.

PMID- 15261458
TI  - SDR grafting of a murine antibody using multiple human germline templates to
      minimize its immunogenicity.
AB  - The humanization of mAbs by complementarity-determining region (CDR)-grafting has
      become a standard procedure to improve the clinical utility of xenogeneic Abs by
      reducing human anti-murine Ab (HAMA) responses elicited in patients. However, CDR
      grafted humanized Abs may still evoke anti-V region responses when administered
      in patients. To minimize anti-V region responses, the Ab may be humanized by
      grafting onto the human templates only the specificity-determining residues
      (SDRs), the residues that are essential for the surface complementarity of the Ab
      and its ligand. Typically, humanization of an Ab, whether by CDR or SDR grafting,
      involves the use of a single human template for the entire VL or VH domain of an
      Ab. We hypothesized, however, that the homology between the human template
      sequences and mAb to be humanized may be maximized by using templates from
      multiple human germline sequences corresponding to the different segments of the
      variable domain. This could be more advantageous in reducing the potential
      immunogenicity of the humanized Ab. This report describes the SDR grafting of the
      murine anti-carcinoembryonic antigen (CEA) mAb COL-1 using three different human
      germline V-kappa sequences as templates for the VL CDRs and another human
      template for the VL frameworks. In competition RIAs, the SDR-grafted COL-1 (HuCOL
      1SDR) completely inhibited the binding of radiolabeled murine COL-1 (mCOL-1) to
      CEA, and showed that its binding affinity is comparable to that of the CDR
      grafted Ab (HuCOL-1). The HuCOL-1SDR showed similar binding reactivity to the CEA
      expressed on the surface of a tumor cell line as the HuCOL-1. More importantly,
      compared to HuCOL-1 and the "abbreviated" CDR-grafted Ab, HuCOL-1SDR showed lower
      reactivity to patients' sera carrying anti-V region Abs to mCOL-1. HuCOL-1SDR,
      which shows a lower sera reactivity than that of the parental Abs while retaining
      its Ag-binding property, is a potentially useful clinical reagent. To the best of
      our knowledge, this is the first time a VL or VH domain of an Ab has been
      humanized by grafting the SDRs onto a human template comprised of several Ab
      sequences. We have shown that humanization of an Ab can be optimized using
      multiple human templates for a single variable domain of an Ab. This approach
      maximizes the homology between the target Ab and the human templates in both the
      frameworks and the CDRs by choosing as the template the human sequence that
      displays the highest local sequence identity to the frameworks and to each of the
      CDRs of the target Ab.

PMID- 15261459
TI  - STAT-1 is activated by IL-4 and IL-13 in multiple cell types.
AB  - While interleukin-4 (IL-4) and interleukin-13 (IL-13) can utilize a common
      receptor, composed of IL-4Ralpha and IL-13Ralpha1, IL-4 can also signal through a
      receptor with IL-4Ralpha and the common gamma chain (gammaC) as its subunits. IL
      4 and IL-13 have been reported to elicit similar biological effects in a number
      of settings, including stimulating Ig isotype switching to IgE and inducing
      chemokines and cytokines in a variety of cell types whereas, depending on the
      receptor expression on responder cells, differential effects such as induction of
      type II helper T cell differentiation by IL-4 but not by IL-13 are also well
      documented. Recent data suggest distinct roles for these two cytokines in the 'in
      vivo' pathology of airway inflammatory diseases such as asthma. In this study, we
      examined the possibility of differential signaling by IL-4 and IL-13 on cells of
      the airway, by comparing expression of receptor chains and activation of
      different Signal Transducer and Activator of Transcription (STAT) family members.
      Five primary cultured cell lines representing four non-immune human lung tissue
      cell types (smooth muscle, epithelium, endothelium, and fibroblast) were
      utilized. While we readily detected expression of IL-4 Ralpha and IL-13Ralpha1 in
      all five cell lines, gammaC was not detectable in any of these cell lines.
      Consistent with previous reports, we detected STAT-6 activation in all five
      airway tissue cell lines examined in response to both cytokines. In addition, we
      also consistently detected STAT-1 activation in all of these cells. This
      observation was extended to include lymphoid as well as myeloid cells that
      express also gammaC chain. In conclusion, while the study found no differences in
      STAT activation in response to the two cytokines, the data show that in addition
      to STAT-6 activation, STAT-1 activation is also a part of the integral signaling
      pathways utilized by IL-4 and IL-13.

PMID- 15261460
TI  - Hypoallergenic and T cell reactive analogue peptides of bovine serum albumin, the
      major beef allergen.
AB  - We recently identified IgE-binding epitopes of bovine serum albumin (BSA), the
      major beef allergen, and found that the major epitope structure contains an EXXV
      motif. Here we report hypoallergenic analogue peptides of BSA that preserve T
      cell reactivity to retain the capacity to induce immunotolerance. Substitution of
      the glutamic acid in the EXXV sequence to aspartic acid leads to a remarkable
      reduction of IgE-binding ability and induces potent T cell proliferation.
      Moreover, in response to the substitutions, the production of INF-gamma is
      markedly increased compared with that elicited by the native peptides. Therefore,
      these analogue peptides represent potential candidates for specific
      immunotherapy.

PMID- 15261461
TI  - Characterization of a new C-type lectin from common carp Cyprinus carpio.
AB  - A new C-type lectin with putative mannose specificity was identified from the
      expressed sequence tag (EST) analysis of cDNA library from common carp head
      kidney (HK), stimulated with concanavalin A and lipopolysaccharide (LPS) during a
      routine EST analysis. The full sequence of 627 bp was identified by 5'-rapid
      amplification of cDNA ends. The gene is composed of 146 amino acid residues,
      including an 18-residue signal peptide for secretion and a single carbohydrate
      recognition domain of approximately 118 residues typical of C-type lectins. Based
      on the predicted structure, this is a calcium dependent C-type lectin with
      putative mannose specificity suggested by the presence of an EPN motif. By
      hemagglutination assay, the mannose specificity of the Ca-CTL was determined.
      Reverse transcription (RT) PCR analysis demonstrated the expression of Ca-CTL
      mRNA in the hematopoietic organs and also the level of expression increased with
      LPS induction. Localization studies by in situ hybridization showed the presence
      of transcripts in the organs.

PMID- 15261462
TI  - Complex regulation of the Csk homologous kinase (Chk) by IL-4 family cytokines
      and IFN-gamma in human peripheral blood monocytes.
AB  - Csk homologous kinase (Chk) is a tyrosine kinase that shares homology with Csk
      and, like Csk, has the potential to inhibit src-family kinase function through
      phosphorylation. In myeloid lineage cells, Chk expression is dependent on
      monocytic differentiation. IL-4 and IL-13 are cytokines involved in monocytic
      differentiation that have recently been shown to induce Chk expression in
      peripheral blood monocytes (PBMs). In this study, we show that two other members
      of the IL-4 family, IL-3 and GM-CSF, can also induce Chk expression at RNA and
      protein levels. Interestingly, Chk induction is both blocked and reversed by IFN
      gamma treatment. Additionally, a short pretreatment with IFN-gamma is sufficient
      to prevent Chk induction, and the effects of IFN-gamma are dependent on protein
      synthesis. Collectively, these results suggest that activation of Chk expression
      and signaling may have a role in the IL-4 family-mediated differentiation of
      myeloid cells, and inhibition of Chk activation may be one mechanism by which IFN
      gamma alters IL-4-mediated affects.

PMID- 15261463
TI  - Threonine at position 6 is not essential for the immunosuppressive activity of
      HLA-DQ(beta164-172)-hexapeptide.
AB  - It has been previously found that the nonapeptide fragment of human leukocyte
      antigen (HLA)-DQ molecule, located in the beta chain 164-172 with the Thr-Pro-Gln
      Arg-Gly-Asp-Val-Tyr-Thr sequence, suppresses the immune response. The
      hexapeptide: Arg-Gly-Asp-Val-Tyr-Thr was the shortest fragment of HLA-DQ showing
      both cellular and humoral immunosuppressive activity, while the analog deprived
      of the last amino acid (Arg-Gly-Asp-Val-Tyr) showed very weak stimulatory
      activity with respect to the humoral immune response. This suggested that the
      threonine residue in the hexapeptide plays an essential role in
      immunosuppression. In this study, the role of the side chain of threonine residue
      was scrutinized in a series of synthetic analogs in which the Thr residue was
      substituted by various amino acids, amides and methyl ester. The synthesized
      peptides were evaluated for their immunosuppressive activity. Our results
      indicate that the substitutions did not significantly affect the immunomodulatory
      properties, revealing that the threonine side chain is not critical for the
      immunosuppressive potency of the peptides. Interestingly, a simple analogue,
      pentapeptide amide H-Arg-Gly-Asp-Val-Tyr-NH2 possessed high immunosuppressive
      potency, comparable to that of cyclosporine.

PMID- 15261464
TI  - A role for the unfolded protein response in optimizing antibody secretion.
AB  - Terminal differentiation of B lymphocytes into antibody(Ab)-secreting plasma
      cells is marked by a sharp rise in immunoglobulin (Ig) biosynthesis that
      increases demand on the protein folding capacity of the endoplasmic reticulum
      (ER). The unfolded protein response pathway (UPR) allows cells to respond to
      challenging conditions within the ER, in part by the activities of the XBP1 and
      ATF6alpha/beta transcription factors. The UPR is activated in differentiating B
      cells, and XBP1 is required for the generation of Ab-secreting plasma cells.
      Therefore, it has been hypothesized that the UPR mediates ER homeostasis as B
      cells transition into high-rate Ab secretion. We sought to test this hypothesis
      in primary murine splenic B cells stimulated to secrete Ab in vitro. Here, we
      report that enforced expression of a dominant-negative ATF6alpha mutant in
      differentiating B cells reduces the output of secreted IgM and increases improper
      release of IgM assembly intermediates. These data indicate that the UPR functions
      to optimize the efficiency of Ab secretion and provide new insight into the
      fundamental role of the UPR in humoral immunity.

PMID- 15261465
TI  - Characterization of porcine CD19 and anti-CD19 monoclonal antibodies.
AB  - CD19 is an important pan B cell marker and co-stimulatory protein in humans and
      mice. Efforts to further characterize B cell ontogeny in swine have been hampered
      by the lack of monoclonal antibodies (mAb) to valuable surface markers like Vpre
      B, CD19, CD34 and CD43. We report here on the complete nucleotide and deduced
      amino acid sequence of porcine CD19, the cross-reactivity of anti-human CD19
      monoclonals and efforts to prepare anti-porcine CD19 mAb to bacterially-expressed
      products. Porcine CD19 is highly homologous to those in the few other species
      studied, i.e. human, mouse and guinea pig, but only in certain domains. Among the
      14 CD19 exons, homology approaches 90% to human CD19 in exons 6, 9, 11 and 12 and
      is approximately 80% with other species in this region. The highly homologous C
      terminal cytoplasmic region contains nine tyrosines including the YEND/E motif
      that binds the SH2 domain of Fyn. Two different porcine CD19 isoforms that differ
      in their 3' UTRs were identified just as in human CD19. Thus, the signaling
      properties of CD19 may be similar to those in humans. On the other hand, only 60%
      sequence similarity was seen in exons 1-5 that encode the N-terminal
      extracellullar region that is involved in ligand binding and is the target of
      CD19-specific mAb. This probably explains why only 1 of the 17 anti-human CD19
      mAb tested recognized swine B cells. Furthermore, when the extracellular domains
      of CD19 were expressed in E. coli, mAbs to the bacterially-expressed product did
      not recognize CD19 on porcine B cells suggesting that carbohydrate-dependent
      conformation may determine antigenicity.

PMID- 15261466
TI  - The case for prospective longitudinal studies in child maltreatment research:
      commentary on Dube, Williamson, Thompson, Felitti, and Anda (2004).

PMID- 15261467
TI  - The importance of retrospective findings in child maltreatment research.

PMID- 15261468
TI  - Assessing the reliability of retrospective reports of adverse childhood
      experiences among adult HMO members attending a primary care clinic.

PMID- 15261469
TI  - Biochemical markers of brain injury: could they be used as diagnostic adjuncts in
      cases of inflicted traumatic brain injury?
AB  - Child abuse is the leading cause of serious traumatic brain injury (TBI) in
      infants and young children (Billmire & Myers, 1985; Bruce & Zimmerman, 1989). The
      incidence of serious or fatal inflicted traumatic brain injury (iTBI) in children
      < 1 year of age is approximately 1 in 3,300 ( Keenan et al., 2003); since many
      cases of iTBI are of mild or moderate severity, the incidence is probably
      significantly higher. Even at an incidence of 1 in 3,300, iTBI is as common as
      the incidence of cystic fibrosis (CF), the most common genetic recessive disease
      in the Caucasian population. Proper diagnosis of iTBI is difficult even for
      experienced and astute physicians because its presentation can be subtle and
      important historical data are often lacking. As a result, misdiagnosis is common
      and can have catastrophic medical consequences for patients and significant
      financial consequences for society ( Ewing-Cobbs et al., 1998; Jenny, Hymel,
      Pitzen, Reinert, & Hay, 1999). Unlike CF for which there are several well
      established screening tests, there are currently no diagnostic adjuncts to help
      physicians screen for possible iTBI.

PMID- 15261470
TI  - A validation study of the Adolescent Dissociative Experiences Scale.
AB  - OBJECTIVE: The purpose of this study was to further the validation process of the
      Adolescent Dissociative Experiences Scale (A-DES). In this study, a 6-item Likert
      response format with descriptors was used when responding to the A-DES rather
      than the 11-item response format used in the original A-DES. METHOD: The internal
      reliability and construct validity of the A-DES were examined by analyzing the
      relationships between A-DES scores, sexual abuse, and behavior. The sample
      consisted of 65 females ranging in age from 11 to 18 who were categorized into
      two groups. Thirty-four adolescents who were not in therapy and who denied a
      history of traumatic experiences formed the nonclinical group. Thirty-one
      sexually abused adolescents who were currently receiving therapy formed the
      clinical group. The adolescent participants completed the A-DES, their parent or
      guardian completed a measure of behavior (the Child Behavior Checklist-CBCL), and
      the therapists of the clinical adolescents completed a Trauma History Form.
      RESULTS: The A-DES discriminated between the nonclinical and clinical sexually
      abused adolescents. However, in post hoc analyses, the A-DES did not discriminate
      between PTSD adolescents and those with other psychiatric diagnoses. Significant
      moderate correlations were found between the A-DES and the CBCL Total behavior
      problem scale and Internalizing and Externalizing scales. CONCLUSIONS: The A-DES
      items are internally consistent, and the A-DES shows promise for screening
      adolescents for pathological dissociation.

PMID- 15261471
TI  - The interrelatedness of multiple forms of childhood abuse, neglect, and household
      dysfunction.
AB  - OBJECTIVE: Childhood abuse and other adverse childhood experiences (ACEs) have
      historically been studied individually, and relatively little is known about the
      co-occurrence of these events. The purpose of this study is to examine the degree
      to which ACEs co-occur as well as the nature of their co-occurrence. METHOD: We
      used data from 8,629 adult members of a health plan who completed a survey about
      10 ACEs which included: childhood abuse (emotional, physical, and sexual),
      neglect (emotional and physical), witnessing domestic violence, parental marital
      discord, and living with substance abusing, mentally ill, or criminal household
      members. The bivariate relationship between each of these 10 ACEs was assessed,
      and multivariate linear regression models were used to describe the
      interrelatedness of ACEs after adjusting for demographic factors. RESULTS: Two
      thirds of participants reported at least one ACE; 81%-98% of respondents who had
      experienced one ACE reported at least one additional ACE (median: 87%). The
      presence of one ACE significantly increased the prevalence of having additional
      ACEs, elevating the adjusted odds by 2 to 17.7 times (median: 2.8). The observed
      number of respondents with high ACE scores was notably higher than the expected
      number under the assumption of independence of ACEs (p <.0001), confirming the
      statistical interrelatedness of ACEs. CONCLUSIONS: The study provides strong
      evidence that ACEs are interrelated rather than occurring independently.
      Therefore, collecting information about exposure to other ACEs is advisable for
      studies that focus on the consequences of a specific ACE. Assessment of multiple
      ACEs allows for the potential assessment of a graded relationship between these
      childhood exposures and health and social outcomes.

PMID- 15261472
TI  - Psychological sequelae of childhood sexual abuse: abuse-related characteristics,
      coping strategies, and attributional style.
AB  - OBJECTIVE: The aim of this study was to test a model predicting the contribution
      of abuse-related characteristics and mediating variables such as coping and
      attributional style in the development of psychological sequelae in adults
      reporting a history of child sexual abuse (CSA). METHODOLOGY: Two hundred and
      eighty-five males and females from three settings (a nonpatient, psychiatric
      outpatient, and psychiatric inpatient) completed a battery of questionnaires that
      included a (1) Sexual History Questionnaire, (2) Ways of Coping Questionnaire,
      (3) Attributional Style Questionnaire, and (4) the SCL-90-R. RESULTS: Of the 285
      participants, 33% reported unwanted or forced sexual contact before the age of 18
      years. Participants who reported a history of CSA also reported higher levels of
      psychological distress when compared to those who did not report a history of
      abuse. In testing the model concerning the relationship between victim-offender
      characteristics, mediating variables and psychological distress in adulthood; two
      abuse-related characteristics (number of offenders and duration of abuse) were
      found to be directly associated with psychological distress in adulthood. Other
      abuse-related variables (i.e., relation with offender, force, resistance, age of
      onset, participation, and frequency of abuse) were found to be related to
      psychological distress in adulthood through the mediation of various coping
      strategies (i.e., Accepting Responsibility, Confrontive Coping) and attributions
      (i.e., internalization of the abuse). CONCLUSIONS: The results of the present
      study further our understanding regarding the relationship between abuse-related
      characteristics, mediating factors such as coping and attributional style and
      psychological distress in adults with a history of CSA. Future research should
      focus on the development of interventions that focus on variables amenable to
      psychotherapy to ameliorate the psychological sequelae of CSA.

PMID- 15261473
TI  - The use of Ecological Momentary Assessment approaches in the study of sexually
      abused children.

PMID- 15261474
TI  - Hypoxia response elements.

PMID- 15261475
TI  - Hypoxia sensing and pathways of cytosolic Ca2+ increases.
AB  - Oxygen-sensing and reactivity to changes in the concentration of oxygen is a
      fundamental property of cellular physiology. This central role is determined,
      mainly, by, to the fact that oxygen represents the final acceptor of electrons,
      derived from the normal cellular metabolism, at the end of the mitochondrial
      respiratory chain. Despite significant advances in molecular characterization of
      various oxygen-sensitive processes, the nature of the oxygen-sensor molecules and
      the mechanisms that link sensors to effects remains unclear. One such controversy
      is about the role and nature of reactive oxygen species (ROS) changes during
      hypoxia. Irrespective of the mechanisms of oxygen sensing, one of the constant
      early responses to hypoxia in almost all cell types is an increase in
      intracellular Ca2+ ([Ca2+]i). In many instances, this increase is mediated by the
      activation of various plasma membrane Ca2+ conductances. Some of these channels
      have specific Ca2+ permeability (e.g. voltage-operated Ca2+ channels), whereas
      others have non-specific cation conductances and are activated by a variety of
      ligands (ligand-operated channels). In the last decade, a large superfamily of
      channels with significant Ca2+ permeability has been progressively identified and
      characterised: the TRP channels. Through their properties, some groups of the TRP
      channels provide a link to the other hypoxia-activated mechanism of [Ca2+]i
      increase: the release of Ca2+ from intracellular Ca2+ stores. Since the [Ca2+]i
      signals, depending on their localization and intensity, are important regulators
      of the subsequent cellular responses to hypoxia, a deeper understanding of the
      mechanisms through which hypoxia regulate the activity of these pathways that
      increase intracellular Ca2+ could point the way towards the development of new
      therapeutic approaches to reduce or suppress the pathological effects of cellular
      hypoxia, such as those seen in stroke or myocardial ischemia.

PMID- 15261476
TI  - Hypoxic vasorelaxation: Ca2+-dependent and Ca2+-independent mechanisms.
AB  - The mechanisms of oxygen sensing in vascular smooth muscle have been studied
      extensively in a variety of tissue types and the results of these studies
      indicate that the mechanism of hypoxia-induced vasodilation probably involves
      several mechanisms that combined to assure the appropriate response. After a
      short discussion of the regulatory mechanisms for smooth muscle contractility, we
      present the evidence indicating that hypoxic vasorelaxation involves both Ca2+
      dependent and Ca2+-independent mechanisms. More recent experiments using
      proteomic approaches in organ cultures of porcine coronary artery reveal
      important changes evoked by hypoxia in both Ca2+-dependent and Ca2+-independent
      pathways.

PMID- 15261477
TI  - Calcium, mitochondria and oxygen sensing in the pulmonary circulation.
AB  - A key event in hypoxic pulmonary vasoconstriction (HPV) is the elevation in
      smooth muscle intracellular Ca2+ concentration. However, there is controversy
      concerning the source of this Ca2+, the signal transduction pathways involved,
      and the identity of the oxygen sensor. Although there is wide support for the
      hypothesis that hypoxia elicits depolarisation via inhibition of K+ channels, and
      thus promotes Ca2+ entry through L-type channels, a significant number of studies
      are inconsistent with this mechanism being either the sole or even major means by
      which Ca2+ is elevated during HPV. There is strong evidence that intracellular
      Ca2+ stores play a critical role, and voltage-independent Ca2+ entry mechanisms
      including capacitative Ca2+ entry (CCE) have also been implicated. There is
      renewed interest in the role of mitochondria in HPV, both in terms of modulators
      of Ca2+ homeostasis per se and as oxygen sensors. There is however considerable
      uncertainty concerning the mechanisms involved in the latter, with proposals for
      changes in redox couples and both an increase and decrease in mitochondrial
      production of reactive oxygen species (ROS). In this article we review the
      evidence for and against involvement of such mechanisms in HPV, and propose a
      model for the regulation of intracellular [Ca2+] in pulmonary artery during
      hypoxia in which the mitochondria play a central role.

PMID- 15261478
TI  - Metabolic stages, mitochondria and calcium in hypoxic/ischemic brain damage.
AB  - Cerebral hypoxia/ischemia leads to mitochondrial dysfunction due to lack of
      oxygen leaving the glycolytic metabolism as a main pathway for ATP production.
      Inhibition of mitochondrial respiration thus triggers generation of lactate and
      hydrogen ions (H+), and furthermore dramatically reduces ATP generation leading
      to disregulation of cellular ion metabolism with subsequent intracellular calcium
      accumulation. Upon reperfusion, when mitochondrial dysfunction is (at least
      partially) reversed by restoring cerebral oxygen supply, bioenergetic metabolism
      recovers and brain cells are able to re-institute their normal ionic homeostatic
      mechanisms. However, the initial restoration of normal mitochondrial function may
      be only transient and followed by a secondary, delayed perturbation of
      mitochondrial respiratory performance seen as a decrease in cellular ATP levels
      and known as "secondary energy failure". There have been several mechanisms
      considered responsible for delayed post-ischemic mitochondrial failure, the
      mitochondrial permeability transition (MPT) being one that is considered
      important. Although the amount of calcium available during early reperfusion in
      vivo is limited, relative to the amount needed to trigger the MPT in vitro; the
      additional intracellular conditions (of acidosis, high phosphate, and low adenine
      nucleotideae levels) prevailing during reperfusion, favor MPT pore opening in
      vivo. Furthermore, the cellular redistribution and/or changes in the
      intracellular levels of pro-apoptotic proteins can alter mitochondrial function
      and initiate apoptotic cell death. Thus, mitochondria seem play an important role
      in orchestrating cell death mechanisms following hypoxia/ischemia. However, it is
      still not clear which are the key mechanisms that cause mitochondrial dysfunction
      and lead ultimately to cell death, and which have more secondary nature to brain
      damage acting as aggravating factors.

PMID- 15261479
TI  - In, out, shake it all about: elevation of [Ca2+]i during acute cerebral
      ischaemia.
AB  - Because of the extensive second messenger role played by calcium, free
      intracellular calcium levels are strictly regulated. Under normal physiological
      conditions, this is achieved through a combination of restricted calcium entry,
      efficient efflux and restricted intracellular mobility. Overall, the process of
      regulating free calcium is dependent on ATP derived from oxidative metabolism.
      Under conditions of cerebral ischaemia, ATP levels fall rapidly and calcium
      homeostasis becomes significantly disturbed resulting in the initiation of
      calcium-dependent neurodegenerative processes. In this review, the mechanisms
      underlying physiological calcium homeostasis and the links between calcium
      disregulation and neurodegeneration will be discussed.

PMID- 15261480
TI  - Calcium and pH homeostasis in neurons during hypoxia and ischemia.
AB  - One of the important events during hypoxia or ischemia in the brain (or other
      organs for that matter, including the myocardium) is the accumulation of Ca2+
      ions intracellularly. Although various studies have shown various sources of and
      routes for Ca2+ entry and accumulation, it is clear now that it is likely that
      there is a multitude rather than a single mechanism for this accumulation. In
      this review, we highlight this Ca2+ accumulation during low O2 states and discuss
      some of the mechanisms leading to accumulation for two main reasons: (a) an
      accumulation of Ca2+ in the cytosol has been proven to be deleterious for cell
      function although this accumulation of Ca2+ and consequences represent only a
      limited view of events that can lead to cell injury during such stress and (b)
      developing therapeutic strategies involving the reduction or elimination of this
      accumulation depends, by and large, on the mechanism of entry. In addition to
      reviewing some of these Ca2+ events, we will also review the relation between pH
      (H+) and Ca2+ since these two ions and their regulation are tied to each other in
      a major way. For example, extracellular acidosis, which can occur during
      ischemia, has a remarkable effect on the function of some of the Ca2+ entry
      routes.

PMID- 15261481
TI  - Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury.
AB  - Acute ischemic and brain injury is triggered by excitotoxic elevation of
      intraneuronal Ca2+ followed by reoxygenation-dependent oxidative stress,
      metabolic failure, and cell death. Studies performed in vitro with neurons
      exposed to excitotoxic concentrations of glutamate demonstrate an initial rise in
      cytosolic [Ca2+], followed by a reduction to a normal, albeit slightly elevated
      concentration. This reduction in cytosolic [Ca2+] is due partially to active,
      respiration-dependent mitochondrial Ca2+ sequestration. Within minutes to an hour
      following the initial Ca2+ transient, most neurons undergo delayed Ca2+
      deregulation characterized by a dramatic rise in cytosolic Ca2+. This prelethal
      secondary rise in Ca2+ is due to influx across the plasma membrane but is
      dependent on the initial mitochondrial Ca2+ uptake and associated oxidative
      stress. Mitochondrial Ca2+ uptake can stimulate the net production of reactive
      oxygen species (ROS) through activation of the membrane permeability transition,
      release of cytochrome c, respiratory inhibition, release of pyridine nucleotides,
      and loss of intramitochondrial glutathione necessary for detoxification of
      peroxides. Targets of mitochondrially derived ROS may include plasma membrane
      Ca2+ channels that mediate excitotoxic delayed Ca2+ deregulation.

PMID- 15261482
TI  - Role of nitric oxide after brain ischaemia.
AB  - Ischaemic stroke is the second or third leading cause of death in developed
      countries. In the last two decades substantial research and efforts have been
      made to understand the biochemical mechanisms involved in brain damage and to
      develop new treatments. The evidence suggests that nitric oxide (NO) can exert
      both protective and deleterious effects depending on factors such as the NOS
      isoform and the cell type by which NO is produced or the temporal stage after the
      onset of the ischaemic brain injury. Immediately after brain ischaemia, NO
      release from eNOS is protective mainly by promoting vasodilation; however, after
      ischaemia develops, NO produced by overactivation of nNOS and, later, NO release
      by de novo expression of iNOS contribute to the brain damage. This review article
      summarizes experimental and clinical data supporting the dual role of NO in brain
      ischaemia and the mechanisms by which NO is regulated after brain ischaemia. We
      also review NO-based therapeutic strategies for stroke treatment, not only those
      directly linked with the NO pathway such as NO donors and NOS inhibitors but also
      those partially related like statins, aspirin or lubeluzole.

PMID- 15261483
TI  - Calcium signaling and neuronal vulnerability to ischemia in the striatum.
AB  - Neurons express extremely different sensitivity to ischemic insults. The neuronal
      vulnerability is region-specific and the striatum is among the most susceptible
      areas to ischemic damage. Projecting GABAergic medium-sized neurons are very
      sensitive to energy metabolism impairment, whereas interneurons are selectively
      spared. However, the reasons for this differential vulnerability are largely
      unknown. Calcium ions (Ca2+) are important intracellular messengers enabling
      several physiological processes. However, excessive Ca2+ influx from the
      extracellular space or release from internal stores can elevate Ca2+ to levels
      that exceed the capacity of single neurons to appropriately buffer such overload.
      This capacity also appears to be a peculiar feature of single neuronal subtypes.
      This review will provide a brief survey of the ionic basis underlying the
      differential responses to in vitro ischemia of distinct striatal neuronal
      subtypes, mainly focusing on the role of Ca2+. The potential relevance of these
      findings in the development of therapeutic strategies for acute stroke will be
      discussed.

PMID- 15261484
TI  - Ca2+-dependent proteases in ischemic neuronal death: a conserved 'calpain
      cathepsin cascade' from nematodes to primates.
AB  - From rodents to primates, transient global brain ischemia is a well known cause
      of delayed neuronal death of the vulnerable neurons including cornu Ammonis 1
      (CA1) pyramidal cells of the hippocampus. Previous reports using the rodent
      experimental paradigm indicated that apoptosis is a main contributor to such
      ischemic neuronal death. In primates, however, the detailed molecular mechanism
      of ischemic neuronal death still remains obscure. Recent data suggest that
      necrosis rather than apoptosis appear to be the crucial component of the damage
      to the nervous system during human ischemic injuries and neurodegenerative
      diseases. Currently, necrotic neuronal death mediated by Ca2+-dependent cysteine
      proteases, is becoming accepted to underlie the pathology of neurodegenerative
      conditions from the nematode Caenorhabditis elegans to primates. This paper
      reviews the role of cysteine proteases such as caspase, calpain and cathepsin in
      order to clarify the mechanism of ischemic neuronal death being triggered by the
      unspecific digestion of lysosomal proteases.

PMID- 15261485
TI  - Glial perspectives of metabolic states during cerebral hypoxia--calcium
      regulation and metabolic energy.
AB  - Cooperation between astrocytes and neurons is a unique interaction between two
      highly specialized cell types of the brain. Therefore, lack of nutrient supply
      during ischemia requires tight coordination of metabolism between astrocytes and
      neurons to keep the brain functions intact. To understand the impact of energy
      limitation on astrocytes, the functions of astrocytes have to be considered: (i)
      supplementation of neuronal cells, (ii) modulation of the extracellular milieu,
      mainly of the glutamate level, and (iii) elimination of reactive oxygen species
      (ROS). In cultured astrocytes and neurons inhibition of oxidative
      phosphorylation, using rotenone, was tested. Interestingly, this had only a
      negligible effect on Ca2+ homeostasis in astrocytes, even in combination with a
      severe glutamate stress. In contrast, in neurons glutamate in the presence of
      rotenone induced Ca2+ deregulation. Ca2+ homeostasis is very critical for cell
      survival. A massive and prolonged Ca2+ rise will lead to deregulation of many
      processes in such a way that the cells affected can hardly survive. Ca2+
      homeostasis depends on the energy-consuming processes, which maintain the steep
      gradient between intracellular and extracellular Ca2+ concentration. Deprivation
      of oxygen and glucose during ischemia leads to a depletion of ATP in the brain,
      due to inhibited glycolytic and mitochondrial activity, whereas energy-consuming
      processes like ion pumps drain the ATP pools. On the other hand, specific
      mechanisms can protect brain structures against the massive insult of ischemia.
      Glycogen, stored in astrocytes, can maintain both neurons and astrocytes alive
      during short limitation of oxygen and glucose. Moreover, astrocytes can fuel ATP
      generation by providing lactate for neurons.

PMID- 15261487
TI  - On the role of Ca2+ in cerebral ischemic preconditioning.
AB  - Cerebral ischemic preconditioning (IPC) represents a potent endogenous method of
      inducing tolerance to otherwise lethal ischemia, both in in vivo and in vitro
      models. Investigation into the mechanism of this phenomenon has yet again
      transformed the way that neuroscientists view Ca2+. Generally viewed as an agent
      of neuronal death, particularly within an excitotoxic setting of cerebral
      ischemia, Ca2+ is now regarded as a key mediator of IPC. Classification of the
      role of Ca2+ in IPC defies simple description, but seems to possess a stimulatory
      role during the tolerance-inducing ischemia and an inhibitory or modulatory role
      during or following the second normally lethal ischemia.

PMID- 15261486
TI  - Cellular neuroprotective mechanisms in cerebral ischemia: Bcl-2 family proteins
      and protection of mitochondrial function.
AB  - Mitochondria are central to brain cell response to ischemia, with critical roles
      in generation of ATP, production of free radicals, and regulation of apoptotic
      cell death. Changes in the permeability of the outer mitochondrial membrane to
      regulators of apoptosis can control ischemic cell death and this permeability is
      directly controlled by the Bcl-2 family of proteins. The Bcl-2 family regulate
      apoptosis by several mechanisms including affecting the formation of apoptotic
      protein-conducting pores in the outer mitochondrial membrane. The anti-apoptotic
      protein Bcl-2 improves neuron survival following various insults, and is
      protective even when administered after stroke onset in a rat model of focal
      ischemia. Despite intense study, the precise molecular mechanisms underlying
      protection by the anti-apoptotic members of the Bcl-2 family are not completely
      understood. This review focuses on the mechanisms by which Bcl-2 family members
      control the permeability of the mitochondrial membrane and influence other
      aspects of mitochondrial function after brain ischemia, concluding with
      discussion of the potential use of Bcl-2 for the treatment of cerebral ischemia.

PMID- 15261488
TI  - Nitric oxide and cerebral ischemic preconditioning.
AB  - Nitric oxide (NO) is an important mediator of cerebral blood flow and metabolism.
      As a vasodilator, NO regulates cerebral blood flow, and couples regional brain
      perfusion with metabolic activity. Following cerebral ischemia, NO levels rise
      significantly due to activation of neuronal nitric oxide synthase by NMDA
      receptor mediated calcium entry. Depending on its tissue and enzymatic source, NO
      may be protective or toxic. This article reviews the effects of NO following
      cerebral ischemia, the signaling pathways through which NO acts, and its
      potential roles in cerebral ischemic preconditioning.

PMID- 15261489
TI  - The role of calcium in hypoxia-induced signal transduction and gene expression.
AB  - Mammalian cells require a constant supply of oxygen in order to maintain adequate
      energy production, which is essential for maintaining normal function and for
      ensuring cell survival. Sustained hypoxia can result in cell death. Sophisticated
      mechanisms have therefore evolved which allow cells to respond and adapt to
      hypoxia. Specialized oxygen-sensing cells have the ability to detect changes in
      oxygen tension and transduce this signal into organ system functions that enhance
      the delivery of oxygen to tissue in a wide variety of different organisms. An
      increase in intracellular calcium levels is a primary response of many cell types
      to hypoxia/ischemia. The response to hypoxia is complex and involves the
      regulation of multiple signaling pathways and coordinated expression of perhaps
      hundreds of genes. This review discusses the role of calcium in hypoxia-induced
      regulation of signal transduction pathways and gene expression. An understanding
      of the molecular events initiated by changes in intracellular calcium will lead
      to the development of therapeutic approaches toward the treatment of
      hypoxic/ischemic diseases and tumors.

PMID- 15261490
TI  - Ion channel regulation by chronic hypoxia in models of acute oxygen sensing.
AB  - Several potentially life-threatening cardiovascular and respiratory disorders
      result in prolonged deprivation of oxygen, which in turn results in significant
      cellular adaptation, or remodelling. An important component of this functional
      adaptation arises as a direct consequence of altered ion channel expression by
      chronic hypoxia. In this review, we discuss current understanding of this hypoxic
      remodelling process, with particular reference to regulation of L-type Ca2+
      channels and high-conductance, Ca2+-sensitive K+ (BK) channels. In systems where
      this remodelling occurs, changes in functional expression of these particular
      channels evokes marked alteration in, or responses to, Ca2+-dependent events.
      Evidence to date indicates that channel expression can be modulated at the
      transcriptional level but, additionally, that crucial post-transcriptional events
      are also regulated by chronic hypoxia. Importantly, such remodelling is, in some
      cases, strongly associated with production of amyloid peptides of Alzheimer's
      disease, implicating chronic hypoxia as a causative factor in the progression of
      specific pathology. Moreover, subtle changes in functional expression of BK
      channels implicates chronic hypoxia as an important regulator of cell
      excitability.

PMID- 15261492
TI  - The Unruptured Intracranial Aneurysm Study-II: a critique of the second study.

PMID- 15261493
TI  - ISUIA-II: the need to share more data.

PMID- 15261494
TI  - Possible harmful effects on central nervous system cells in the use of
      physiological saline as an irrigant during neurosurgical procedures.
AB  - BACKGROUND: Physiologic saline is routinely used as an irrigant in neurosurgery
      especially in Japan. Cerebrospinal fluid (CSF) differs from physiologic saline in
      its concentration of inorganic salts, osmolality, and pH and is completely
      different insofar as it contains glucose, protein, cholesterol, and other lipids.
      The present study was designed to compare the possible functional and morphologic
      deleterious influence of these differences on cultured rat neural cells using
      saline (S), Ringer's solution with glucose (Lactec G, LG; Otsuka Pharmaceutical
      Co.; Tokyo, Japan) and without glucose (Lactec, L; Otsuka Pharmaceutical Co.),
      and an artificial CSF (ACSF). METHODS: Primary cultured rat neurons and
      astrocytes were divided into five groups according to the medium used, the four
      experimental groups (ACSF, L, LG, and S) and one control group (C). At various
      time points up to 24 hours, the rhodamine 123 uptake by neuronal or astrocytic
      cellular mitochondria was evaluated as cell function assessment. Morphologic
      assessment for both neuron and astrocyte culture was carried out with scanning
      electron microscopy (SEM) at the 24-hour time point. RESULTS: SEM showed little
      difference between the C and ACSF groups, whereas morphologic deterioration was
      particularly severe in the S group for both neurons and astrocytes. In the case
      of neuronal mitochondrial activity, the L and S groups demonstrated respectively
      severe and some deterioration, particularly in the mitochondria of the neuronal
      processes. The deleterious effects in mitochondrial activity of the S group were
      even more apparent in the astrocytic cells. CONCLUSION: These results suggest
      that physiologic saline, when used as an irrigant in neurologic surgery, might in
      some circumstances cause damage to exposed and compromised neural cells.

PMID- 15261496
TI  - Linear accelerator thalamotomy.
AB  - BACKGROUND: The capability of performing functional radiosurgery lesions in the
      brain using a dedicated linear accelerator (LINAC) have not yet been
      demonstrated. This study evaluates modern LINAC technology for the creation of a
      sharp, small and functionally eloquent lesion in the thalamus. METHODS: Three
      patients underwent thalamotomy using a dedicated linear accelerator to
      radiosurgery, 2 females and 1 male, ages were 52, 53, and 73 years. Two patients
      presented with unilateral poststroke central pain and 1 with unilateral upper
      extremity pain secondary to metastatic infiltration of the brachial plexus.
      Maximal doses varied from 150 to 200 Gy, delivered by a 5-mm diameter collimator
      and 5 to 8 noncoplanar arcs evenly distributed. RESULTS: All patients gained
      substantial relief of their pain. They were able to reduce their medications and
      improve their activity levels. The patient with end-stage metastatic disease died
      of his malignancy 2 weeks after the treatment. One patient presented with
      recurrence of the pain 4 months after the treatment. No clinical complications
      were noticed. CONCLUSIONS: A dedicated linear accelerator is able to perform a
      precise and circumscribed lesion in the thalamus for pain control. Moreover, it
      proved to be safe, because no complications were observed. For patients using
      chronic anticoagulant therapy or with severe disabilities caused by cardiac,
      pulmonary or malignant diseases, this technique represents an alternative of
      treatment to radiofrequency thalamotomy.

PMID- 15261499
TI  - Angiographic assessment of cerebral circulation time for outcome prediction in
      patients with subarachnoid hemorrhage.
AB  - BACKGROUND: In the acute stage following subarachnoid hemorrhage (SAH), prolonged
      cerebral circulation time reflects increased intracranial pressure (ICP), which
      can lead to irreversible brain damage. We evaluated the ability of cerebral
      circulation time to predict outcome in SAH patients. METHODS: We prospectively
      studied 40 consecutive patients treated for SAH according to standard intensive
      care guidelines. Lateral views in preoperative carotid digital subtraction
      arteriograms (DSA) were used to determine arteriovenous transit time (AVTT),
      defined as interval from initial opacification of the intracranial internal
      carotid artery to that of the Rolandic vein. We then analyzed relationship of
      AVTT to other prognostic parameters and outcome. RESULTS: AVTT depended on
      initial Glasgow Coma Scale score (GCS), ranging from 3.4 to 8.0 seconds (mean:
      5.4) when initial GCS was 13 to 15; from 4.5 to 8.7 seconds (mean: 6.4) when
      initial GCS was 7 to 12; and from 5.8 to 15.0 seconds (mean: 9.1 seconds,
      excluding angiograms with nonfilling) when initial GCS was 3 to 6. AVTT
      correlated significantly with prognosis, longer AVTT predicting poorer outcome.
      No patient with an AVTT above 12 seconds recovered to a functioning state.
      CONCLUSIONS: AVTT obtained from routinely performed acute-phase DSA in SAH
      patients reflects ICP and functional prognosis, representing a cost-effective,
      practical, and reliable outcome predictor.

PMID- 15261501
TI  - Compound depressed skull fractures involving a venous sinus.
AB  - BACKGROUND: Neurosurgeons have always been wary about operating on compound
      depressed skull fractures overlying a venous sinus. Conservative treatment of
      such lesions, however, must be weighed against the benefits of surgery reducing
      sepsis, mass effect, and improving cosmetic appearance. There has been little
      published on this surgical problem and with this in mind, we undertook a review
      of the clinical features, management and outcome of patients presenting to our
      unit with a depressed fracture over a venous sinus. METHODS: A retrospective
      review of all patients presenting with a compound depressed skull fracture over a
      venous sinus from 1997 to 2000. Computer tomography scans and patient records
      were used. RESULTS: Of the 146 patients with depressed skull fractures, 27 (18%)
      were eligible. Of the 27 patients, 14 were treated conservatively and 13 were
      treated with surgery. Intra-operative difficulty was experienced in 6 (46%) of
      those taken to the operating room. Of those treated conservatively 14% developed
      sepsis. CONCLUSION: We feel that a more conservative approach to fractures
      involving a sinus is warranted. If the wound is not contaminated, the risk of
      infection is low. Surgery exposes the patient to the very real risk of massive
      hemorrhage. In instances where there is a clear need for surgery, such as the
      presence of mass effect or deep contamination, adequate precautions should be
      taken.

PMID- 15261505
TI  - Neurophysiological monitoring for safe surgical tethered cord syndrome release in
      adults.
AB  - BACKGROUND: Release of tethered spinal cord by sectioning of the filum terminale
      carries a significant risk of injury to the neighboring motor and sensory nerve
      roots. Intraoperative neurophysiological monitoring techniques can help to
      minimize these adverse neurologic outcomes. METHODS: We performed a retrospective
      review of 67 consecutive patients undergoing tethered cord release. We excluded
      52 pediatric patients which limited our study to 15 adult patients treated during
      a four year period, including patients with a thick filum, low lying conus,
      myelomeningocele, filum tumor, spinal cord malformation, and/or lipoma. Clinical
      outcomes were determined from postoperative follow-up visits. Two patients were
      lost to follow up and were excluded from the clinical outcome analysis.
      Electrical stimulation of the filum terminale and lumbo-sacral nerve roots in
      conjunction with electromyogram (EMG) recording was performed intraoperatively.
      RESULTS: The mean electrical threshold for EMG response during stimulation of the
      filum terminale was 37.1 volts (V), range 15 to 100 V. In comparison, the lowest
      threshold obtained by direct stimulation of the ventral nerve roots was a mean of
      1.46 V, with a range of 0.1 to 7 V. More than 70% of the patients studied
      demonstrated a filum to motor root threshold ratio of 100:1 or greater. No
      patient developed new neurologic symptoms or signs postoperatively. Bowel and
      bladder function improved in 46% of patients, back pain in 39% and motor function
      in 31%. Eight percent reported decline in bladder control and worsening back pain
      postoperatively. CONCLUSIONS: The often dramatic difference in the threshold of
      the filum terminale and adjacent motor nerve roots (100:1) helps to identify,
      isolate, and safely section the filum terminale. Tethered cord release using
      intraoperative neurophysiological monitoring is safe and in the majority of cases
      leads to improvement or at least, stabilization of neurologic function.
      Monitoring prevented intraoperative nerve root injury that might have resulted in
      immediate onset of new neurologic deficits caused by the surgical procedure.

PMID- 15261507
TI  - Spontaneous regression of Langerhans cell histiocytosis: a case report.
AB  - BACKGROUND: Spontaneous regression of Langerhans cell histiocytosis (LCH) has
      been reported in skin, bone, and pulmonary lesions. However, such phenomena in
      the central nervous system (CNS) have not been described previously. CASE
      DESCRIPTION: A case of LCH in the CNS with spontaneous regression is reported. A
      2-year-old boy presented with general convulsion followed by frequent vomiting
      and diabetes insipidus. Magnetic resonance imaging (MRI) scan revealed numerous
      multifocal nodules predominantly in the left frontal lobe. The patient underwent
      surgery to remove part of the frontal lesion. Subsequent to surgery, residual
      lesions showed regression without any additional treatment, and clinical symptoms
      also subsided. The multiple lesions disappeared completely and did not relapse
      during 5-year observation. CONCLUSION: Surgical resection and/or adjuvant therapy
      such as radiation and chemotherapy has been performed for the treatment of LCH in
      the CNS. However, there may be a subgroup of patients with multifocal brain LCH
      that regress spontaneously. Further clinical study is required to establish the
      natural course and prognostic factors of this disease.

PMID- 15261511
TI  - Three-dimensional anisotropy contrast imaging of gliomatosis cerebri: two case
      reports.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) can provide a preoperative diagnosis
      of gliomatosis cerebri, but the findings sometimes do not correspond with the
      clinical symptoms or histologic findings. CASE DESCRIPTION: Three-dimensional
      anisotropy contrast (3DAC) imaging was used to assess damage to the neuronal
      fibers in two patients with gliomatosis cerebri who presented with only mental
      deterioration. Conventional MRI depicted markedly abnormal findings consisting of
      widespread areas of abnormally high signal intensity in the corpus callosum and
      in the bilateral white matter in both cases. In contrast, 3-D AC imaging showed
      no abnormality except for small dark areas in the corpus callosum or white
      matter. CONCLUSION: 3-D AC imaging provides more accurate information about
      damage to the neuronal fibers in cases of gliomatosis cerebri than other MRI
      techniques.

PMID- 15261509
TI  - Therapeutic vancomycin monitoring in children with hydrocephalus during treatment
      of shunt infections.
AB  - BACKGROUND: The successful treatment of shunt infections in children with
      hydrocephalus is still an important problem. Diagnosis of shunt colonization is
      often very difficult. To treat serious central nervous system (CNS) infections,
      intraventricular therapy with antibiotics is necessary to reach adequate
      cerebrospinal fluid (CSF) concentrations and eradicate the infection. For optimal
      management of shunt infections the concentration of administered antibiotics in
      CSF should be measured. The antibiotic dosing could be modified in the individual
      patient after pharmacokinetic studies. METHODS: In our studies, vancomycin was
      applied to 10 children with hydrocephalus (including 6 with a myelomeningocele)
      for therapeutic purposes in shunt infections. The drug was administered IV and/or
      intraventricularly. During treatment the concentration of vancomycin in CSF was
      determined by fluorescence polarization immunoassay (FPIA) method. RESULTS:
      Considerable differences in vancomycin concentrations after the same
      intraventricular antibiotic administration were observed depending on the
      patient. The vancomycin levels determined at study state were often much higher
      than the therapeutic recommended range, and the biologic half-life period
      (T(1/2)) of vancomycin in cerebrospinal fluid after intraventricular
      administration was prolonged. CONCLUSIONS: The results of our studies give
      information about the pharmacokinetics of vancomycin in CSF in a group of
      children with hydrocephalus after intraventricular administration of the drug. In
      our investigation, the administration of doses smaller than 5 mg/24 hours is
      appropriate when the removed volume of CSF will be 20 to 30 mL/24 hours.

PMID- 15261513
TI  - Spontaneous cervical epidural hematoma: case report and literature review.
AB  - BACKGROUND: Spontaneously occurring epidural hematomas for which no etiology is
      identified are rare phenomenon. These are often neurosurgical emergencies;
      therefore, prompt diagnosis and treatment are paramount. Because of the rarity of
      this condition, we have illustrated in this recent case its presentation,
      evaluation and management. METHODS: A 63-year-old male presented to our emergency
      room with right-sided hemiparesis and contralateral hypesthesia, consistent with
      a C5 Brown-Sequard syndrome. An initial evaluation for cerebral infarction was
      unremarkable, including a negative brain magnetic resonance image. Further
      imaging revealed a cervical epidural hematoma of unknown etiology. RESULTS: The
      patient underwent emergent laminectomy for decompression and evacuation of the
      hematoma within 24 hours of his presentation to the emergency room. The patient's
      symptoms improved remarkably after surgery and a 4-month follow-up imaging
      evaluation revealed no recurrence of his hematoma. CONCLUSION: This report
      highlights the various presentations, evaluation, and management options for this
      rare diagnosis. It emphasizes the necessity of prompt diagnosis for possible
      emergent intervention.

PMID- 15261515
TI  - Idiopathic spinal cord herniation: a new theory of pathogenesis.
AB  - BACKGROUND: Idiopathic spinal cord herniation is a rare entity that has been
      described more frequently over the past few years. Its pathophysiology remains
      obscure, however. METHODS: We report a case of spinal cord herniation and review
      the literature extensively. In view of our review, we try to determine the
      clinical features of the condition and the diagnostic measures used, with
      emphasis on the role of magnetic resonance (MR) phase-contrast CSF study. The
      factors affecting the outcome of the condition are also studied including time
      and type of presentation, as well as the surgical procedure performed. The
      pathophysiological mechanisms behind spontaneous herniation are discussed, and a
      new hypothesis is proposed. RESULTS: Idiopathic spinal cord herniation occurs in
      the middle-aged adult, with a preponderance of patients being female. Brown
      Sequard syndrome is the most common clinical presentation and usually progresses
      to spastic paraparesis. MRI typically shows a ventral kink in the thoracic cord,
      with MR phase-contrast imaging proving an important addition to exclude an
      arachnoid cyst. Better outcomes were noted in the patients treated earlier, and
      in those with no spasticity. Widening the dural defect seems to afford better
      results compared to grafting of the defect. The prognosis is favorable after
      correction, though a vertebral body herniation variant may be associated with
      worse outcome. In view of the chronology of events and imaging studies in our
      patient, we hypothesize that herniation occurs as an acquired phenomenon where an
      inflammatory process results in adherence between the spinal cord and the dura,
      with erosion, formation of a dural defect, and then later herniation occurring
      with cerebral spinal fluid (CSF) pulsations. CONCLUSIONS: Idiopathic herniation
      of the spinal cord should be recognized and treated early to reach a favorable
      outcome. It seems to be an acquired condition likely caused by an inflammatory
      event, the nature of which is to be determined.

PMID- 15261518
TI  - Intracranial metastasis of hepatocellular carcinoma: review of 45 cases.
AB  - BACKGROUND: Although extrahepatic metastasis of hepatocellular carcinoma (HCC) is
      not uncommon, intracranial metastasis is relatively rare. METHODS: We reviewed
      HCC cases admitted in our hospital in the past 16 years, and there were only 45
      cases with clinically diagnosed intracranial metastasis. Their age ranged from 14
      to 82 years with the peak in the 3rd and 4th decades, which is much younger than
      the average age of the HCC patients. RESULTS: Of the 45 patients, 39 (39/45,
      86.7%) had hepatitis B related and 20 (20/45, 44.4%) had cirrhosis of the liver.
      Intracranial hemorrhage as the initial manifestation was common in our series
      (18/45, 40%). Hemiparesis was found in 14 cases, scalp mass in 9 cases, headache
      in 13 cases, diplopia in 3 cases (1 ultimately became totally blind), homonymous
      hemianopsia in 2 cases, dysarthria in 3 cases, gait disturbance in 1 case,
      seizure in 3 cases, and aphasia in 1 case. The modes of therapy for patients with
      intracranial metastasis included conservative medical treatment only or surgical
      excision and/or radiotherapy. In this series, elevated AFP was noted in 32
      patients, and alpha fetoprotein higher than several thousands was even noted in
      30 patients; extraordinary high level (>70000) was also seen in more than one
      half of the patients. CONCLUSIONS: HCC patients with intracranial metastasis
      presented a very poor prognosis. In general, they deteriorated rapidly and
      expired without active treatment. Surgical excision of the intracranial
      metastatic mass, followed by radiotherapy, can improve the life quality and
      prolong survival time.

PMID- 15261520
TI  - Opting out of Medicare.

PMID- 15261519
TI  - Falcotentorial plasmacytoma: a case report.
AB  - This is the case report of a 45-year-old lady presenting with headache and
      papilledema. Investigations revealed falcotentorial plasmacytoma. Tumor was
      removed and adjuvant radiotherapy was given. This is curative. There are only 2
      previous cases of plasmacytoma involving falx and tentorium simultaneously. En
      plaque meningioma is the close differential diagnosis.

PMID- 15261521
TI  - Socialized (free) medical care in Cuba part I: a poor state of health!

PMID- 15261523
TI  - New approaches to modelling and analysis of biochemical reactions, pathways and
      networks.

PMID- 15261524
TI  - Quantitative analysis of signaling networks.
AB  - The response of biological cells to environmental change is coordinated by
      protein-based signaling networks. These networks are to be found in both
      prokaryotes and eukaryotes. In eukaryotes, the signaling networks can be highly
      complex, some networks comprising of 60 or more proteins. The fundamental motif
      that has been found in all signaling networks is the protein
      phosphorylation/dephosphorylation cycle--the cascade cycle. At this time, the
      computational function of many of the signaling networks is poorly understood.
      However, it is clear that it is possible to construct a huge variety of control
      and computational circuits, both analog and digital from combinations of the
      cascade cycle. In this review, we will summarize the great versatility of the
      simple cascade cycle as a computational unit and towards the end give two
      examples, one prokaryotic chemotaxis circuit and the other, the eukaryotic MAPK
      cascade.

PMID- 15261525
TI  - Transcriptional control networks of cell differentiation: insights from helper T
      lymphocytes.
AB  - Coordinated programs of gene expression during cell differentiation can be
      controlled by master transcription factors. The differentiation of helper T (Th)
      lymphocytes during the immune response has been shown to occur along alternative
      pathways designated as Th1 and Th2. Induction of the Th1 and Th2 pathways is
      associated with the conversely regulated expression of the master factors T-bet
      and GATA-3, respectively. Both autoactivation and inhibition of GATA-3 play a
      crucial role in this process. We develop mathematical models of the underlying
      regulatory networks to provide a framework for the analysis of experimental data.
      Modeling concepts for gene expression dynamics are introduced, and paradigms for
      the behavior of gene-regulatory networks are reviewed. A mechanistic model for
      the regulation of GATA-3 in Th cells is developed that accounts for
      autoactivation and regulation by external differentiation signals. This system
      works as a bistable switch that enables the triggering of a differentiation
      program by transient inductive signals. GATA-3 inhibitors (such as FOG-1 and ROG)
      modulate GATA-3 expression by yet unidentified mechanisms. Three potential modes
      of inhibition, sequestration by a binding protein, repression of basal
      transcription, and repression of autoactivation, are predicted to have distinct,
      and strongly concentration-dependent, regulatory effects on GATA-3 dynamics.
      Based on these results, we develop a model for the cross-regulation of the
      alternative Th1 and Th2 differentiation programs which are governed by the
      dynamics of T-bet and GATA-3, respectively. The steady states of this model
      correlate with naive, Th1-polarized, and Th2-polarized phenotypes. Our analysis
      makes predictions on the stability of the Th1 and Th2 programs and raises
      questions on the relation between transcription factor regulation and epigenetic
      determination in cell differentiation.

PMID- 15261526
TI  - Mathematical and computational techniques to deduce complex biochemical reaction
      mechanisms.
AB  - Time series data can now be routinely collected for biochemical reaction
      pathways, and recently, several methods have been proposed to infer reaction
      mechanisms for metabolic pathways and networks. In this paper we provide a survey
      of mathematical techniques for determining reaction mechanisms for time series
      data on the concentration or abundance of different reacting components, with
      little prior information about the pathways involved.

PMID- 15261527
TI  - Reaction-diffusion models of development with state-dependent chemical diffusion
      coefficients.
AB  - Reaction-diffusion models are widely used to model developmental processes. The
      great majority of current models invoke constant diffusion coefficients. However,
      the diffusion of metabolites or signals through tissues is frequently such that
      this assumption may reasonably be questioned. We consider several different
      physical mechanisms leading to effective diffusion coefficients in biological
      tissues which vary with the local conditions, including models in which
      juxtacrine signaling results in the diffusion of a signal in the absence of
      material transport. We develop a mathematical formalism for transforming local
      transport laws into diffusive terms. This procedure is appropriate when the
      typical length scale over which the concentrations change significantly is much
      greater than the dimensions of a cell. We review previous developmental models
      which considered the possibility of state-dependent diffusion coefficients. We
      also provide a few new motivating examples.

PMID- 15261528
TI  - Processes controlling metal transport and retention as metal-contaminated
      groundwaters efflux through estuarine sediments.
AB  - Factors affecting the transport and retention of Cd, Cr, Cu, Ni, Pb and Zn in
      acidic groundwaters as they pass through estuarine sediments were investigated
      using column experiments. Acidic groundwaters caused the rapid dissolution of
      iron sulfide (AVS) and other iron and manganese phases from sediments that are
      important for metal binding and buffering. Metal breakthrough to overlying water
      occurred in the order of Ni>Zn>Cd>>Cu>>Cr/Pb. Metal transport increased as the
      sediment permeability increased, reflecting the low resistance to flow caused by
      larger sand-sized particles and the decreased abundance of metal adsorption sites
      on these materials. Metal mobility increased as the groundwater pH decreased, as
      flow rate or metal concentrations increased, and as the exposure duration
      increased. Groundwater Cr and Pb were promptly attenuated by the sediments, the
      mobility of Cu was low and decreased rapidly as sediment pH increased above 4.5,
      while Cd, Ni and Zn were the most easily transported to the surface sediments and
      released to the overlying waters. For groundwaters of pH 3, metal migration
      velocities through sandy sediments were generally 0.5-2% (Cr, Pb), 1-6% (Cu) and
      4-13% (Cd, Ni, Zn) of the total groundwater velocity (9-700 m/yr). The oxidative
      precipitation of Fe(II) and Mn(II) in the groundwaters did not affect metal
      mobility through the sediments. The results indicated that the efflux of acidic
      and metal-contaminated groundwater through estuarine sediments would affect
      organisms resident in sandy sediments more greatly than organisms resident in
      fine-grained, silty, sediments.

PMID- 15261529
TI  - Chemical and enzymatic interactions of Direct Black 38 and Direct Brown 1 on
      release of carcinogenic amines.
AB  - Release of amine products from azo compounds is of considerable interest, since
      most of the metabolized amine products have toxic and carcinogenic characters.
      Moreover, most of the azo dyes are extensively used as coloring agents in inks,
      textiles, leathers, food and pharmaceutical industries. The present study
      emphasis on the quantification and comparison of amines released from water
      soluble dyes by (i) extra cellular protein (ECP) of Streptomyces sp. SS07 and by
      (ii) chemical methods. It has been observed that both the methods release
      considerable quantities of similar type of amine products. Release of amine
      compounds by ECP and chemical reduction in acid and alkaline sweat medium from a
      leather garment sample was also assessed. ECP (0.7852 mg protein/mg of ECP)
      releases benzidine and 4-amino biphenyl from Direct Black 38 and Direct Brown 1
      as stable products at pH 9.2 and at 37 degrees C for a contact period of 24 h. On
      comparison with chemical reduction, it was observed that about 5-20% increase in
      the release of amine products by ECP was observed. However, more than 60% of
      amine products were released by chemical method from leather garment samples than
      direct treatment with ECP.

PMID- 15261530
TI  - Adsorption of bisphenol-A, 17 beta-estradiole and 17 alpha-ethinylestradiole to
      sewage sludge.
AB  - Adsorption of bisphenol-A (CAS 85-05-7), 17 beta-estradiole (CAS 50-28-2) and 17
      alpha-ethinylestradiole (CAS 57-63-6) to activated and to inactivated sludge from
      wastewater treatment plants (WWTPs) was investigated, thus allowing to
      distinguish between pure adsorption and biosorption. For the investigated
      substances the determination of the adsorption kinetics is based on experiments
      performed according to the OECD guideline 106 and on free concentration
      measurements in the liquid phase. The description of the adsorption behaviour
      occurred via Freundlich Adsorption Isotherms. Additionally specific adsorption
      coefficients KD, KOM and KOC were calculated. The results of these calculations
      were compared to KOC values obtained with a HPLC method according to the OECD
      guideline 121. All substances showed a high adsorption affinity to the adsorbent
      and in spite of the application of very high initial concentrations no saturation
      level could be reached. Within a contact time of 24 h, no difference between the
      adsorption to activated and inactivated sludge could be detected. The calculated
      KD values were within a range of about KD = 1000 l kg(-1) for the investigated
      compounds and showed a clear concentration dependency in the case of bisphenol-A.
      Adsorption was also found to depend on pH. The experimentally determined KOC
      values of the investigated substances were significantly higher than the results
      obtained with the HPLC method described in OECD guideline 121.

PMID- 15261531
TI  - Formation of bound residues by naphthalene and cis-naphthalene-1,2-dihydrodiol.
AB  - The formation of bound residues by naphthalene and its metabolite, cis
      naphthalene-1,2-dihydrodiol, in a sediment (1% OC), a silty loam soil (2.9% OC)
      and a peat (26% OC) was examined. The experiments were carried out under both
      sterile and nonsterile conditions for up to 35 days. The samples containing bound
      contaminant were hydrolyzed at an alkaline pH and fractionated using 3,000 and
      500 Da molecular weight cutoff ultrafiltration membranes in series. The results
      for all the geosorbents examined showed that bound residue formation is low for
      naphthalene and between 5 and 20 times higher for the metabolite. The amount of
      bound residues released by hydrolysis was higher for the metabolite than for the
      parent compound for all the samples. The molecular weight distribution of bound
      radioactivity after hydrolysis showed binding to the high molecular weight
      components of the sediment organic matter and to the low molecular weight
      components for soil and peat organic matter when incubated with cis-naphthalene
      1,2-dihydrodiol. Experiments performed with naphthalene-UL-(14)C showed larger
      amounts of bound residue found than in experiments with naphthalene-1-(14)C.

PMID- 15261532
TI  - Environmental distribution of uranium and other trace elements at selected Kosovo
      sites.
AB  - This paper reports the results of a study using lichens as biomonitors to
      investigate the environmental distribution of uranium and other trace elements at
      selected Kosovo sites. The results suggested that the use of depleted uranium
      (DU) ammunitions in Kosovo did not cause a diffuse environmental contamination in
      such a way to have caused a detectable U enrichment in lichens. Also isotopic
      (235)U/(238)U measurements did not indicate the presence of DU particles in
      lichens. The present results also provided no indication of intense environmental
      contamination by the other trace elements analyzed, with the exception of
      Kosovska Mitrovica, where a diffuse environmental contamination by several heavy
      elements such as Pb, Zn, As and Cd was found.

PMID- 15261533
TI  - Profile analysis of ambient and source emitted particle-bound polycyclic aromatic
      hydrocarbons from three sites in northern Greece.
AB  - Polycyclic aromatic hydrocarbons (PAHs) adsorbed to ambient PM(10) were
      determined at three sites in Thessaloniki, northern Greece, during the period
      June 1997-July 1998. Ambient PAH profiles exhibited significant seasonal and
      spatial variations. Source PAH profiles were obtained for a number of urban,
      industrial and geological sources including cement, fertilizer and asphalt
      production, quarry operations, metal electroplating, metal welding and tempering,
      steel manufacture, lead and bronze smelters, metal scrap incineration, oil
      burning, non-catalyst equipped passenger cars, diesel fueled taxies and buses,
      paved road dust and soil dust. Principal component analysis (PCA) and diagnostic
      ratios were employed to compare ambient and source PAH profiles in an attempt to
      recognize compositional patterns. Similarities between the ambient PAH profiles
      and the profiles of certain sources, such as vehicular emissions, oil burning and
      metal industries, were identified.

PMID- 15261534
TI  - Removal of azo and anthraquinone dyes from aqueous solutions by Eichhornia
      Crassipes.
AB  - The rate of adsorption of two azo and four anthraquinone anionic dyes on
      Eichhornia Crassipes (E.C.) has been studied. Raw E.C. and three aminated
      derivatives of E.C. with different nitrogen percent were used as dye adsorbents.
      The parameters studied include the amount of substrate, shaking time, chemical
      structure, concentration of dyestuff and pH of dyeing bath. Simple kinetic
      adsorption models of dynamics and adsorption parameters for the Langmuir and
      Freundlich isotherms were determined. A higher nitrogen percent of aminated E.C.
      showed a higher adsorption capacity than other derivatives. The kinetic
      adsorption models indicate that the decolourization was complete in a relatively
      short time (10 min) and the reaction taking place is of the first order. The
      equilibrium data fit well with the Freundlich model of adsorption for the six
      dyes. Only dye IV (C.I.A Acid Blue 25) conform both Freundlich and Langmuir
      adsorption isotherms.

PMID- 15261535
TI  - Modified Lagrangian method for modeling water quality in distribution systems.
AB  - Previous work has shown that Lagrangian methods are more efficient for modeling
      the transport of chemicals in a water distribution system. Two such methods, the
      Lagrangian Time-Driven Method (TDM) and Event-Driven Method (EDM) are compared
      for varying concentration tolerance and computational water quality time step. A
      new hybrid method (EDMNET) is developed which improves the accuracy of the
      Lagrangian methods. All the above methods are incorporated in an existing
      hydraulic simulation model. The integrated model is run for different network
      problems under varying conditions. The TDM-generated solutions are affected by
      both concentration tolerance and water quality time step, whereas EDM solutions
      are dependent on concentration tolerance. The EDMNET solutions are less sensitive
      to variations in these parameters. The threshold solutions are determined for all
      the methods and compared. The hybrid method simulates the nodal concentrations
      accurately with least maximum segmentation of network and reasonable
      computational effort as compared to the other Lagrangian methods.

PMID- 15261536
TI  - Elevated levels of arsenic in the sediments of an urban pond: sources,
      distribution and water quality impacts.
AB  - The discovery of significantly elevated levels of arsenic (As) in the sediments
      of Spy Pond motivated us to identify the principal As source and to investigate
      the extent of contamination within the pond. Spy Pond is located in Arlington
      (MA, USA), a residential and commercial town with no known history of As use by
      industry or agriculture. Spy Pond is a kettle-hole pond composed of two basins
      (north and south) separated by a shallow sill. Sediment cores from the two basins
      were analyzed for As content by instrumental neutron activation analysis and
      dated by measuring 210Pb activity. The As concentration profiles for the north
      and south basins had maxima that dated to approximately 1962 and approximately
      1956, respectively. These dates are consistent with records of arsenical
      herbicide use, which indicate that between 1960-1968 sodium arsenite (NaAsO2) and
      arsenic oxide (As2O3) were applied to the pond to control aquatic macrophytes.
      Estimates of As loadings to the two basins-- approximately 410 kg ( approximately
      32 kg ha(-1)) to the north and approximately 5800 kg ( approximately 580 kg ha(
      1)) to the south--are consistent with the range of application rates reported for
      other lakes treated with arsenical herbicides. To determine the extent of As
      contamination in the pond, 68 surface sediment samples were analyzed by energy
      dispersive X-ray fluorescence. Arsenic levels ranged from 1 to 2600 ppm in the
      north basin (n = 49) and from 120 to 1100 ppm in the south basin (n = 19).
      Background sediment-As levels for the area are 10-40 ppm. The highest
      concentrations of As in the sediments of Spy Pond are comparable to levels
      measured in lakes contaminated with chemical manufacturing and mining wastes.
      These results are discussed with respect to As remobilization and sediment
      treatment measures planned for the pond.

PMID- 15261537
TI  - Enhancement of photocatalytic activity by metal deposition: characterisation and
      photonic efficiency of Pt, Au and Pd deposited on TiO2 catalyst.
AB  - Pt, Au and Pd deposited TiO2 have been prepared and characterised by surface
      analytical methods such as surface area, XRD, and scanning electron micrograph
      and photophysical characterisation by diffuse reflectance spectroscopy. The
      photocatalytic activity of the doped catalysts was ascertained by the photo
      oxidation of leather dye, acid green 16 in aqueous solution illuminated with low
      pressure mercury lamp ( approximately 254 nm). The effect of metal contents on
      the photocatalytic activity was investigated. The highest photonic efficiency was
      observed with metal deposition level of less than 1 wt%.

PMID- 15261538
TI  - The combined effect of step-feed and recycling on RBC performance.
AB  - The effect of step-feed and recycling on the efficiency of treatment in rotating
      biological contractors (RBCs) was investigated. Experiments were conducted on a
      RBC system consisting of two three-stage units. The two units were operated in
      parallel, one unit as a control with a single feed point and the other in a step
      feed mode. Seven experimental runs were conducted, using a simple synthetic
      wastewater, in which hydraulic loading rates were maintained constant at about
      0.094 m3/m2d and variable COD concentrations (800-1200 mg/L), NH3-N
      concentrations (104-116 mg/L), step-feed ratios (60/40 and 70/30), and
      recirculation modes. Results indicate that improvements in the treatment
      efficiencies of RBC systems may be attained by operating the system in a step
      feed mode as compared to a single point feed mode. Further improvements may also
      be obtained by inducing effluent recirculation to the inlet stage. In both cases,
      levels of improvement have shown to be more pronounced for NH3-N removals and DO
      residual concentrations as compared to COD removals. The combined effect of step
      feed and recirculation of system effluent on NH3-N removal efficiencies is
      appreciable. Comparing removal efficiencies between the control, step feed and
      the combined step-feed/recirculation modes shows an increase of about 26%. For
      COD removals, the effect is not that pronounced as the results for the combined
      modes of operation indicate a limited increase in overall removal efficiency of
      about 3%. Supplementing step feed by a recircutation system also markedly
      improved DO residuals in stages 1 and 2 and to a lower extent in stage 3 of the
      system. Changing the ratio in the step feed system from 60/40% to 70/30%
      exhibited a slight improvement in NH3-N removal efficiencies as well as improved
      residual DO concentrations but very limited effect on COD removals. The use of a
      simple synthetic wastewater in the experiments may limit extrapolation of the
      findings to actual operation.

PMID- 15261539
TI  - A study on pesticide runoff from paddy fields to a river in rural region--1:
      field survey of pesticide runoff in the Kozakura River, Japan.
AB  - Runoff characteristics of nine kinds of herbicides from paddy fields were
      surveyed in the Kozakura River, that is one of the tributaries flowing into the
      Lake of Kasumigaura, over a period of 23 April to 30 June (before and after rice
      transplantation) of year. The flow rates of river water and the concentrations of
      herbicides in the river water were measured every day in May and every 2 days in
      April and June at six survey sites along the river. The runoff characteristics of
      herbicides were elucidated by taking account of the rainfall data, the detailed
      application data (application date and quantities of herbicides applied to each
      paddy field in a region), and their physico-chemical properties. The runoff rates
      (the runoff/application amounts ratio) were calculated for each herbicide,
      resulting in the range of 8.2-22.4%. The runoff rates were correlated fairly well
      with octanol-water partition coefficient, logP(ow), rather than with water
      solubility of herbicides.

PMID- 15261540
TI  - A study on pesticide runoff from paddy fields to a river in rural region--2:
      development and application of a mathematical model.
AB  - A mathematical model was developed to predict the runoff of pesticides from paddy
      fields to a river in a rural region. The model comprises three submodels: (1)
      submodel for river flow, (2) submodel for pesticide behavior in paddy fields, (3)
      submodel for pesticide behavior in a river. The tank model was applied to predict
      the river flow and the paddy water. In order to reproduce the actual behavior of
      pesticides in paddy fields, the kinetics of the transport and reaction mechanisms
      of pesticides applied to paddy fields were considered in the model. The model was
      applied to the Kozakura River Basin where the detailed field survey was
      conducted. The model reflected well the runoff characteristics of pesticides
      obtained from the detailed field survey.

PMID- 15261541
TI  - Removal of carbon and nutrients from domestic wastewater using a low investment,
      integrated treatment concept.
AB  - An integrated chemical-physical-biological treatment concept for the low-cost
      treatment of domestic wastewater is proposed. Domestic wastewater was subjected
      to a chemically enhanced primary treatment (CEPT), followed by treatment in an
      upflow anaerobic sludge blanket (UASB) reactor. In addition, a regenerable
      zeolite was used to remove NH4+, either after CEPT pretreatment or after
      biological treatment in the UASB reactor. The CEPT pretreatment consisted of the
      addition of a coagulant (FeCl3) and an anionic organic flocculant and removed on
      average 73% of the total chemical oxygen demand (COD(t)), 85% of the total
      suspended solids, and 80% of PO4(3-) present in the wastewater. The UASB system,
      which consequently received a low COD(t) input of approximately 140 mg/L, was
      operated using a volumetric loading rate of 0.4 g COD(t)/L. d (hydraulic
      retention time [HRT]=10 h) and 0.7 g COD(t)/L. d (HRT=5 h). For these conditions,
      the system removed about 55% of the COD(t) in its influent, thus producing an
      effluent with a low COD(t) of approximately 50 mg/L. The zeolite, when applied in
      batch mode before the UASB reactor, removed approximately 45% of the NH4+,
      whereas its application as a post-treatment cartridge resulted in almost 100%
      NH4+ removal. The simple design and relatively low operating costs, due to low
      costs of added chemicals and low energy input (estimated at Euro 0.07-0.1 per m3
      wastewater treated), combined with excellent treatment performance, means that
      this system can be used as a novel domestic wastewater treatment system for
      developing countries. Therefore, the system is called a Low Investment Sewage
      Treatment (LIST) system.

PMID- 15261542
TI  - Removal of water pollutants with activated carbons prepared from H3PO4 activation
      of lignin from kraft black liquors.
AB  - Activated carbons with a high BET surface area and a well-developed porosity have
      been prepared from pyrolysis of H3PO4-impregnated lignin precipitated from kraft
      black liquors. Impregnation ratios within the range of 1-3 and activation
      temperatures of 623-873 K have been used, giving rise to carbons with different
      porous and surface chemical structure. Increasing the activation temperature and
      the impregnation ratio leads to a widening of the porous structure with a higher
      relative contribution of mesoporosity. The potential application of these carbons
      for the removal of water pollutants has been investigated by measuring their
      adsorption capacities for phenol, 2,4,5-trichlorophenol and Cr (VI) as
      representative of toxic contaminants found in industrial wastewaters. The results
      obtained compare well and even favorably with those reported in the literature
      for other activated carbons. An impregnation ratio and an activation temperature
      around 2 g H3PO4/g lignin and 700 K, respectively, are recommended as the best
      combination of operating conditions to prepare activated carbons for aqueous
      phase applications although at lower values of these two variables carbons with
      good adsorption capacities are also obtained.

PMID- 15261543
TI  - The effect of a wildfire on stream water quality and catchment water yield in a
      tropical savanna excluded from fire for 10 years (Kakadu National Park, North
      Australia).
AB  - The wet/dry tropics of the Australian savannas are particularly prone to fire due
      to the highly seasonal rainfall and accumulation of grassy fuels. The effect of
      an early dry season wildfire (May, 1998) on the water quality of a seasonally
      flowing stream (December-June) was examined for a lowland savanna forest in
      Kakadu National Park (northern Australia) which had remained unburnt for 10
      years. The water quality variables assessed were: total and volatile suspended
      sediment, phosphorus, nitrogen, iron and manganese. Compared to three years of
      pre-fire water quality data and 5 years of stream flow data, there was no
      detectable impact of the wildfire on the volume of stream flow, mean
      concentrations and the total mass transported by the stream for each water
      quality variable, except possibly nitrogen. The limited effect on water quality
      is attributed primarily to the timing of the wildfire and the low intensity
      relative to fires later in the dry season (September). The retention of canopy
      cover and the accumulation of leaf litter following the wildfire, and the
      catchment's gently undulating terrain all contributed to the negligible impact on
      water quality. Early dry season fires appear to be a viable management option for
      reducing accumulated fuel loads and hence reducing the risk of destructive
      wildfires later in the dry season.

PMID- 15261544
TI  - Magnetite seeded precipitation of phosphate.
AB  - Seeded precipitation of Ca phosphate on magnetite mineral (Fe3O4) surfaces was
      investigated using a Jar Test system in supersaturated solutions at 20 degrees C
      and ionic strength 0.01 mol l(-1) with relative super saturation, 12.0-20.0 for
      HAP. pH of the solution, initial phosphorus concentration and molar Ca/P ratio
      were investigated as the main parameters, which effect the seeded precipitation
      of Ca phosphate. Results showed that there is no pronounced effect of magnetite
      seed, neither positive nor negative on the amount of calcium phosphate
      precipitation. pH was found to be the main parameter that determines the
      phosphate precipitated onto the seed surface. Increasing of the pH of
      precipitation reaction was resulted in the decrease in percentage amount of
      phosphate precipitated onto seed surfaces to total precipitation (magnetite
      seeded precipitation efficiency). It was concluded that the pH dependence of
      magnetite-seeded precipitation should be considered in the light of its effect on
      the supersaturated conditions of solution. Saturation index (SI) of solution with
      respect to the precipitate phase was considered the driving force for the
      precipitation. A simulation programme PHREEQC (Version 2) was employed to
      calculate the Saturation-index with respect to hydroxyapatite (HAP) of the
      chemically defined precipitation system. It was found a good relationship between
      SI of solution with respect to HAP and the magnetite seeded precipitation
      efficiency, a second order polynomial function. Results showed that more
      favorable solution conditions for precipitation (higher SI values of solution)
      causes homogenous nucleation whereas heterogeneous nucleation led to a higher
      magnetite seeded precipitation efficiency.

PMID- 15261545
TI  - Atrazine removal using adsorption and electrochemical regeneration.
AB  - This paper demonstrates the removal of atrazine using a novel carbon-based
      adsorbent to below 1.0 microg l(-1) and its subsequent electrochemical
      regeneration in a simple electrochemical cell. Effective electrochemical
      regeneration can be achieved with a treatment time as low as 20 min over a number
      of adsorption/regeneration cycles using laboratory-prepared solutions. The
      results suggest that electrochemical modification of the particulate surface on
      electrochemical regeneration can result in adsorptive capacities three times
      greater than originally achieved.

PMID- 15261546
TI  - Regeneration of brewery waste water using nanofiltration.
AB  - The brewing industry is a large consumer of groundwater for brewing, rinsing and
      cooling purposes. As regulations become more and more stringent and the cost of
      water increases, water recycling gains interest. This paper investigates the
      possibilities of nanofiltration for the treatment of brewery waste water streams
      in view of recycling. Four different water streams (waste water after biological
      treatment, bottle rinsing water, rinsing water of the brewing room and rinsing
      water of the bright beer reservoir) were filtered with four different
      nanofiltration membranes (UTC-20, UTC-60, Desal-HL-51 and Desal-5-DK). The
      results for the biologically treated waste water were the most promising. For the
      other streams, rejection of organics was insufficient to obtain the required
      quality, mainly due to the high concentrations of organics such as ethanol in the
      feed water. Over the periods considered (3 h) only moderate flux decline (10-40%)
      was observed for most membranes and feed solutions. For Desal-5-DK at high pH, an
      increase of the flux was observed.

PMID- 15261547
TI  - UV disinfection in a model distribution system:; biofilm growth and microbial
      community.
AB  - Two model distribution systems were operated in parallel to investigate the
      impact of UV disinfection on water distribution system biofilms and microbial
      community composition. One system received an influent irradiated with UV light,
      whereas the control received the same influent with no treatment. The biofilm in
      the UV system, as compared to the control, was more responsive (i.e., had a
      greater increase in steady-state density of heterotrophic bacteria) to the
      increased nutrient availability afforded by a decrease in HRT from 12 to 2 h.
      However, the UV treatment did not have a consistent impact on the biofilm
      community, indicating the processes controlling HPC density were independent of
      the specific strains of bacteria forming the biofilm. There was evidence that
      particle shielding contributed to the survival of UV-susceptible bacteria. This
      hypothesis was consistent with the presence of UV-susceptible bacteria in the UV
      system, as well as the high similarity of the biofilm communities in the UV and
      control systems in one of the experiments. To simulate an intrusion event,
      opportunistic pathogens were added to each system after the biofilm community
      reached steady-state. Opportunistic pathogen attachment was not affected by the
      UV treatment, but was instead correlated to the biofilm density of heterotrophic
      bacteria.

PMID- 15261548
TI  - Runoff-related agricultural impact in relation to macroinvertebrate communities
      of the Lourens River, South Africa.
AB  - A field study at the Lourens River, South Africa, was undertaken during the
      pesticide application period between November 2001 and January 2002 in order to
      investigate the potential relation of agricultural pollution to the aquatic
      macroinvertebrate fauna. The upper regions of the Lourens River were free of
      contamination (LR1), whereas subsequent stretches flowing through a 400-ha
      orchard area (LR2) received transient insecticide peaks. Continuously operating
      suspended-particle samplers as well as flood samplers operating during runoff
      events were used to measure pesticide contamination. In addition, various
      physicochemical and morphological parameters were examined. A survey of the
      macroinvertebrate communities associated with the rocky substrates was carried
      out every three weeks. Community indices were calculated using the South African
      Scoring System (SASS 5) for bioassessment of water quality in rivers. The two
      sites differed in pesticide pollution as well as in average turbidity levels (LR1
      5.5 mg/L; LR2 64.3 mg/L), but were similar in bottom substrate composition and
      most other abiotic factors. At the downstream site (LR2), pesticide values of
      0.05 microg/L azinphos-methyl in water as well as 49 microg/kg azinphos-methyl,
      94 microg/kg chlorpyrifos and 122 microg/kg total endosulfan in suspended
      particles were found during runoff conditions. The macroinvertebrate communities
      of the two sampling sites were similar in terms of number of total individuals,
      but differed significantly (ANOVA) in average number of taxa (LR1 11.7, LR2 8.9).
      Seven out of 17 investigated taxa occurred in significantly reduced numbers or
      were even absent at the downstream site LR2. The community characteristics
      determined by SASS 5 showed a significantly less sensitive community structure at
      the downstream site (TS 41; ASPT 4.6), indicating continuously lower water
      quality compared to site LR1 (TS 80; ASPT 6.9). It is concluded that the Lourens
      River macroinvertebrate communities are affected by agricultural pollution, with
      pesticides and increased turbidity as the most important stressors.

PMID- 15261549
TI  - Evaluation of disinfectant efficacy against biofilm and suspended bacteria in a
      laboratory swimming pool model.
AB  - Laboratory reactor systems designed to model specific environments enable
      researchers to explore environmental dynamics in a more controlled manner. This
      paper describes the design and operation of a reactor system built to model a
      swimming pool in the laboratory. The model included relevant engineering
      parameters such as filter loading and turn-overs per day. The water chemistry in
      the system's bulk water was balanced according to standard recommendations and
      the system was challenged with a bacterial load and synthetic bather insult,
      formulated to represent urine and perspiration. The laboratory model was then
      used to evaluate the efficacy of six chemical treatments against biofilm and
      planktonic bacteria. Results showed that the biofilm was able to accumulate on
      coupons and in the filter systems of reactors treated with either 1-3 mg/L free
      chlorine or 10 mg/L polyhexamethylene biguanide (PHMB). All the treatments tested
      resulted in at least a 4 log reduction in biofilm density when compared to the
      control, but shock treatments were the most effective at controlling biofilm
      accumulation. A once weekly shock dose of 10 mg/L free chlorine resulted in the
      greatest log reduction in biofilm density. The research demonstrated the
      importance of studying a biofilm in addition to the planktonic bacteria to assess
      the microbial dynamics that exist in a swimming pool model.

PMID- 15261550
TI  - Sonolysis of natural phenolic compounds in aqueous solutions: degradation
      pathways and biodegradability.
AB  - The sonochemical degradation in water of p-coumaric acid and p
      hydroxybenzaldehyde, compounds that are commonly found in effluents of
      agricultural origin, was investigated using an 80 kHz horn-type sonicator.
      Experiments were performed at initial concentrations varying between 10 and 100
      mg L(-1), an applied power varying between 75 and 150 W and liquid bulk
      temperatures varying between ambient and 70 degrees C. At the conditions in
      question, substrate removal was found to increase with increasing power and
      decreasing initial concentration and temperature. Addition of 1-butanol as a
      radical scavenger at a concentration of 1000 mg L(-1) nearly completely
      suppressed p-coumaric acid degradation. Conversely, addition of radical promoters
      (Fe2+ ions or H2O2) had a positive effect on removal, thus implying that
      degradation proceeds predominantly via hydroxyl radical-induced reactions.
      Reaction intermediates were determined using liquid and gas chromatography and a
      reaction network for p-coumaric acid degradation is suggested. Shake flask tests
      with activated sludge were performed to assess the aerobic biodegradability (in
      terms of chemical oxygen demand removal) before and after sonochemical treatment.
      At the conditions under consideration, the use of ultrasound enhanced the aerobic
      degradability of the substrates in question.

PMID- 15261552
TI  - Uptake of mercury by thiol-grafted chitosan gel beads.
AB  - This study describes the synthesis and characterization of thiol-grafted chitosan
      beads for use as mercury (Hg) adsorbents. Chitosan flakes were dissolved and
      formed into spherical beads using a phase inversion technique, then crosslinked
      to improve their porosity and chemical stability. Cysteine was grafted onto the
      beads in order to improve the adsorption affinity of Hg to the beads. The beads
      possessed an average diameter of 3.2 mm, porosity of 0.9, specific surface area
      of approximately 100 m2/g, average pore size of approximately 120 angstroms, and
      specific gravity of 2.0. Equilibrium and kinetic uptake experiments were
      conducted to study the uptake of Hg by the beads. The adsorption capacity was
      approximately 8.0 mmol-Hg/g-dry beads at pH 7, and decreased with decreasing pH.
      Hg adsorption kinetics was modeled as radial pore diffusion into a spherical bead
      with nonlinear adsorption. Use of the nonlinear Freundlich isotherm in the
      diffusion equation allowed modeling of the uptake kinetics with a single
      tortuosity factor of 1.5 +/- 0.3 as the fitting parameter for all initial Hg
      concentrations, chitosan loadings, and agitation rates. At agitation rates of 50
      and 75 rpm, where uptake rate was reduced significantly due to the boundary layer
      effect, the mass transfer coefficient at the outside boundary was also used as a
      fitting parameter to model the kinetic data. At agitation rates higher than 150
      rpm, pore diffusion was the rate-limiting step. The beads exhibited a high
      initial uptake rate followed by a slower uptake rate suggesting pore diffusion as
      the rate-determining step especially at high agitation rates. Higher uptake rates
      observed in this study compared to those in a previous study of chitosan-based
      crab shells indicate that dissolution and gel formation increase the porosity and
      pore accessibility of chitosan.

PMID- 15261551
TI  - Monitoring marine recreational water quality using multiple microbial indicators
      in an urban tropical environment.
AB  - The microbial water quality at two beaches, Hobie Beach and Crandon Beach, in
      Miami-Dade County, Florida, USA was measured using multiple microbial indicators
      for the purpose of evaluating correlations between microbes and for identifying
      possible sources of contamination. The indicator microbes chosen for this study
      (enterococci, Escherichia coli, fecal coliform, total coliform and C.
      perfringens) were evaluated through three different sampling efforts. These
      efforts included daily measurements at four locations during a wet season month
      and a dry season month, spatially intensive water sampling during low- and high
      tide periods, and a sand sampling effort. Results indicated that concentrations
      did not vary in a consistent fashion between one indicator microbe and another.
      Daily water quality frequently exceeded guideline levels at Hobie Beach for all
      indicator microbes except for fecal coliform, which never exceeded the guideline.
      Except for total coliform, the concentrations of microbes did not change
      significantly between seasons in spite of the fact that the physical-chemical
      parameters (rainfall, temperature, pH, and salinity) changed significantly
      between the two monitoring periods. Spatially intense water sampling showed that
      the concentrations of microbes were significantly different with distance from
      the shoreline. The highest concentrations were observed at shoreline points and
      decreased at offshore points. Furthermore, the highest concentrations of
      indicator microbe concentrations were observed at high tide, when the wash zone
      area of the beach was submerged. Beach sands within the wash zone tested positive
      for all indicator microbes, thereby suggesting that this zone may serve as the
      source of indicator microbes. Ultimate sources of indicator microbes to this zone
      may include humans, animals, and possibly the survival and regrowth of indicator
      microbes due to the unique environmental conditions found within this zone.
      Overall, the results of this study indicated that the concentrations of indicator
      microbes do not necessarily correlate with one another. Exceedence of water
      quality guidelines, and thus the frequency of beach advisories, depends upon
      which indicator microbe is chosen.

PMID- 15261553
TI  - Comment on "Longitudinal dispersion coefficients in natural channels".

PMID- 15261554
TI  - Immunosuppressive treatment in multiple sclerosis.
AB  - Immunosuppressive therapy has been used to treat multiple sclerosis (MS) for over
      30 years based on the hypothesis that MS is a T cell-mediated autoimmune disease.
      The most commonly used immunosuppressive agents in MS are azathioprine,
      cyclophosphamide, methotrexate, and mitoxantrone. Since the interferons and
      glatiramer acetate have become widely used in MS, immunosuppressive agents have
      found a role given as combination therapy or as monotherapy in instances where
      the interferons and glatiramer acetate are not effective in controlling the
      disease. Like the interferons and glatiramer acetate, immunosuppressive drugs are
      most efficacious in stages of MS that have an inflammatory component as evidenced
      by relapses and/or gadolinium-enhancing lesions on MRI or in patients in earlier
      stages of disease where inflammation predominates over degenerative processes in
      the CNS. There is no evidence of efficacy in primary progressive MS or later
      stages of secondary progressive MS. In our studies of cyclophosphamide, we have
      found that although it is a general immunosuppressant that affects both T cell
      and B cell functions, cyclophosphamide has selective immune effects in MS by
      suppressing IL-12- and Th1-type responses and enhancing Th2/Th3 responses (IL-4,
      IL-10, TGF-beta; eosinophils in peripheral blood). Cyclophosphamide and
      mitoxantrone are the most common immunosuppressive drugs used in patients with
      rapidly worsening MS whose disease is not controlled by beta-interferon or
      glatiramer acetate.

PMID- 15261555
TI  - Immunotherapeutic approaches in multiple sclerosis.
AB  - The progress in understanding the mechanisms of T cell activation, inactivation
      and modulation has been translated into different immunotherapeutic strategies
      aiming at treating multiple sclerosis (MS). Key attack points for selective
      immunointervention in MS include modulation of antigen recognition, costimulation
      blockade, induction of regulatory cells, deviation to non-pathogenic or
      protective responses, neutralization of proinflammatory cytokines and
      administration of anti-inflammatory cytokines. In addition, several attempts have
      been made using less specific forms of immunointervention. The two resounding
      successes in the immunotherapy of MS, IFN-failed and glatiramer acetate, contrast
      with the many attempts, equally based on sound reasoning and promising animal
      data. Nevertheless, antigen-based immunointervention will continue to be tested
      clinically, and we will certainly witness the application of more articulate
      strategies able to selectively target cytokine production by Th1 or Th2 cells or
      to modify the Th1/Th2 balance. Perhaps, an effective manipulation of pathogenic
      and protective cells in MS may eventually rely on a combination of antigen- and
      cytokine-based approaches to selectively target autoreactive T cells and divert
      them from autoaggression. Most importantly, new avenues are opening, such as the
      use of chemokine receptor antagonists, and others look very promising, as
      targeting dendritic cells to favour their capacity to induce regulatory T cells.

PMID- 15261556
TI  - Mechanisms of mitoxantrone in multiple sclerosis--what is known?
AB  - The recent publication of the MIMS-study (Mitoxantrone In Multiple Sclerosis) and
      the approval of several health authorities support the use of mitoxantrone in
      patients with active relapsing-remitting or secondary progressive multiple
      sclerosis. This review provides information on data thus far present on the
      putative mechanisms of action of mitoxantrone in the immunopathogenesis of this
      disabling disease.

PMID- 15261557
TI  - Azathioprine and methotrexate in multiple sclerosis.
AB  - Evidence for the effectiveness of immunosuppressive agents in MS is scanty. There
      are few good quality trials; most have methodological limitations, such as a
      small sample size and short duration. Moreover, there is no consistency in
      treatment regimes, patient groups or outcome measures and the clinical benefits
      remain unclear. Although azathioprine appears to reduce the relapse rate in MS
      patients, its effect on disability progression has not been demonstrated.
      Methotrexate may alter the course of disease favourably in patients with
      progressive MS, but the evidence is again sparse.

PMID- 15261558
TI  - Rationale for the use of mitoxantrone in multiple sclerosis.
AB  - Mitoxantrone is a member of the anthracendione family developed to treat
      malignancies and increasingly used to treat multiple sclerosis (MS). It has been
      studied as a treatment for MS since the late 1980s, and is licensed in a number
      of countries for progressive and worsening MS. Review of the published earlier
      open-label, and more recently of controlled trials suggests that mitoxantrone is
      efficacious in cases of worsening MS that have an inflammatory component as
      evidenced by progression with or without superimposed relapses and/or gadolinium
      (Gd) enhancing magnetic resonance (MR) lesions. Today there is no robust evidence
      of efficacy in primary progressive MS or in later stages of secondary progressive
      MS beyond an EDSS score of 6. Relevant immunomodulatory mechanisms act both on T-
      and B-cell function, and mitoxantrone has selective immune effects in MS by
      decreasing levels of TNF-alpha, IL-2, IL-2R-beta1, IL-10 and IFN-gamma. Adverse
      events include nausea, alopecia, infections, menstrual disorders, risk of
      cardiotoxicity and malignancy. Different regimens are used according to different
      regulatory demands in different countries. The two most commonly used regimens
      are every 3 months intravenous (i.v.) 12 mg/m2 for 2 years or 20 mg mitoxantrone
      (i.v.) combined with 1 g methylprednisolone (i.v.) every 4 weeks for 6 months.
      The cumulative life dose in MS patients is 140 mg/m2. Mitoxantrone is currently
      used as a second line drug in MS patients whose disease is not controlled by beta
      interferon or glatiramer acetate. In this review, we will discuss the clinical
      disease patterns of MS patients who are most likely to benefit from mitoxantrone,
      its magnitude of clinical effect, and limitations of using mitoxantrone in MS.
      Mitoxantrone as a second line therapy in non-responders of beta-interferon and
      glatiramer acetate will be assessed. Recent strategies of combination therapy,
      and the optimal dose regimen will also be discussed.

PMID- 15261559
TI  - The argument against the use of cyclophosphamide and mitoxantrone in the
      treatment of multiple sclerosis.
AB  - Mitoxantrone (MITX) and cyclophosphamide (CPM) are potent immunosuppressive
      agents with efficacy in the treatment of multiple sclerosis (MS). Both agents
      appear effective in those patients with active inflammatory disease but are
      probably less effective in patients with a secondary progressive (SP) course
      dominated by a degenerative component. Given these agents are effective patients
      with active inflammation the question arises as to whether they are more
      effective than high dose interferon therapy. Interferon beta administered at high
      dose and high frequency suppresses enhancing lesions by as much as 90% and brings
      about a 35% decrease in relapse rates in addition to decreasing the progression
      of disability. Interferons have an excellent safety profile even after years of
      administration. What then is the advantage of immunosuppressive agents such as
      cyclophosphamide and mitoxantrone over safer and still effective treatments? The
      answer lies in the magnitude of effect in those with the most active and
      aggressive disease states. While interferons are safe and effective in those with
      mild or moderate inflammatory disease states, they are probably not sufficient to
      bring about control in disease that is highly active and resilient. Both
      mitoxantrone and cyclophosphamide have the ability to suppress inflammation that
      may be resistant to therapy with more conservative agents. Given the safety
      profile of these agents their use should be restricted to those patients with
      aggressive disease resistant to treatment with more conservative agents.

PMID- 15261560
TI  - Corticosteroids treatment.
AB  - Corticosteroids (Cs) are widely used for treatment of multiple sclerosis (MS)
      acute relapses because of the potent immunosuppressive and anti-inflammatory
      properties. As for patients with relapsing-remitting (RR) MS, short-term
      administrations of Cs markedly less severity of symptoms and promote faster
      recovery of clinical attacks. Chronic administrations of Cs significantly
      diminish the formation of T1 hypointense lesions and the progression of brain
      atrophy. As for patients with secondary progressive MS treatment with Cs delays
      the time to onset of sustained disability. Finally the association between
      methylprednisolone and interferon beta (IFNbeta) leads the recovery of active
      lesions at greater extent and reduces the formation of neutralizing antibodies
      (NABs) against IFNbeta in patients with RRMS.

PMID- 15261561
TI  - Autologous hemopoietic stem cell transplantation in the treatment of multiple
      sclerosis: rationale and clinical experience.
AB  - Based on the encouraging results of transplantation in animals with experimental
      autoimmune encephalomyelitis (EAE), small-scale phase I/II trials of autologous
      hematopoietic stem cell transplantation (autoHSCT) were initiated in 1995 for the
      treatment of severe cases of multiple sclerosis (MS). More than 200 patients with
      treatment-resistant multiple sclerosis have been transplanted so far, mainly in
      Europe and the USA. The results of these studies appear promising in terms of
      impact on MRI disease parameters and, to a lesser extent, clinical stabilization
      or even improvement. Despite concerns raised by the morbidity and mortality noted
      in the initial pilot studies, a controlled, randomized, phase III trial of
      autoHSCT against the best currently available treatment, i.e., mitoxantrone,
      seems justified and is under way.

PMID- 15261562
TI  - Hematopoietic stem cell transplantation in multiple sclerosis: experimental
      evidence to rethink the procedures.
AB  - Acute immunosuppression with lymphocytic agents given at maximally tolerated
      doses, followed by hematopoietic stem cell rescue achieved by autologous bone
      marrow or peripheral blood stem cell transplantation (BMT), has proved effective
      in various experimental models of autoimmunity. The rationale for such an
      approach in autoimmune diseases is based on the concept of lymphoablation of self
      reactive lymphocytes followed by de novo immune system reconstitution, which, in
      the presence of the autoantigens in the thymus, may reinduce self-tolerance. Our
      previous work shows that in experimental autoimmune encephalomyelitis (EAE),
      autologous/syngeneic BMT not only prevents the appearance of paralytic signs, but
      can also partially reverse chronic disease and induce long-term, antigen-specific
      tolerance. However, there are serious reservations to be considered when
      interpreting these data and before applying similar protocols in patients with
      multiple sclerosis. (1) The model of EAE is not a completely reliable model of
      multiple sclerosis. (2) In animals with chronic EAE, although further relapses
      were prevented, the established paralysis was usually not reversible. According
      to recent data, in chronic multiple sclerosis (MS) lesions, damage caused by
      axonal loss/transection and cortical/spinal cord atrophy is irreversible and
      probably amenable to immunotherapy. (3) Long-term, antigen-specific tolerance may
      be induced with BMT, but not in all cases; in passively induced CR-EAE, many of
      the mice relapsed upon challenge with myelin antigens, which may indicate that
      the presence of the immunizing, myelin antigens (on the site of immunization)
      during the process of immune reconstitution is critical for induction of
      tolerance. Finally, one should weigh the procedure-related risks (including
      mortality of up to 5%) of bone marrow or peripheral stem cell transplantation
      (SCT). A more radical solution for autoimmunity may involve the use of non
      myeloablative allogeneic transplantation.

PMID- 15261563
TI  - Clinical practice of immunosuppressive treatments in multiple sclerosis: results
      of a second international questionnaire.
AB  - Immunosuppressive treatment is a current practice in MS therapy. Mitoxantrone has
      gained largest acceptance. Differences in clinical indications of mitoxantrone,
      cyclophosphamide, azathioprine and methotrexate are described.

PMID- 15261564
TI  - A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide
      (CTX) for 24 months in patients affected by multiple sclerosis on a background
      therapy with interferon-beta study denomination: CYCLIN.
AB  - The authors present and discuss a new protocol for active multiple sclerosis (MS)
      patients. A double blind randomized controlled multicenter study was planned to
      study the effects of a combination regimen therapy: cyclophosphamide plus beta
      interferon versus beta interferon alone on both relapsing-remitting and secondary
      MS patients with active disease. The primary endpoint of this study is the number
      of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are
      new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy,
      number of patients who were relapse-free, number of patients who improved, yearly
      relapses, quality of life, disability and cognitive impairment, frequency of
      neutralizing antibodies, safety of the combination therapy (cyclophosphamide +
      beta interferon). The study will enroll 225 patients in 25 Italian MS centers.
      Eligible for the study are patients with either relapsing-remitting or secondary
      MS according McDonald criteria on 6-24 months beta interferon treatment with
      active disease (new gadolinium enhancing lesion or who experienced a new relapse
      on beta interferon treatment). Clinical evaluation will be performed every 4
      months, MRI yearly. Vital signs and eventual adverse events will be collected
      monthly. The study will last 36 months, 12 for the enrollment phase and 24 for
      the treatment phase. The study will start on April 2004.

PMID- 15261565
TI  - Preliminary analysis of a trial of pulse cyclophosphamide in IFN-beta-resistant
      active MS.
AB  - This was a randomized, single-blind, parallel-group, multicenter trial in MS
      patients with a history of active disease during IFN-beta treatment. Patients
      were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g
      IV (CY/MP) or methylprednisolone (MP) once monthly for 6 months then followed for
      an additional 18 months. All patients received IFN-beta1a for the 24-month study
      period. The primary endpoint was mean change from baseline in the number of
      gadolinium-enhancing (Gd+) lesions. Secondary endpoints included the percentage
      of patients with Gd+ lesions, change in T2 lesion burden, change in brain
      parenchymal fraction (BPF), time to treatment failure, and cumulative probability
      of relapse. Safety was assessed by the incidence of adverse events and the
      results of blood and urine testing. A higher number of patients completed the
      study in the pulse cyclophosphamide group because approximately half as many of
      these patients became treatment failures (26% vs. 52%, p = 0.03). During the
      infusion phase, the mean number of Gd+ lesions declined 70-80% from baseline in
      the CY group vs. a small increase in MP (p = 0.02 and 0.04 at 3 and 6 months). We
      conclude that pulse cyclophosphamide appears to be well tolerated in combination
      with IFN-beta1a. Pulse cyclophosphamide decreases the number of Gd+ lesions in
      patients with active disease on IFN-beta compared to pulse methylprednisolone
      alone. Six doses of pulse cyclophosphamide in combination with IFN-beta1a both
      prevent and delay clinical disease activity in patients with previously active
      disease on IFN-beta alone. Pulse cyclophosphamide is a therapeutic option as
      rescue therapy for patients thought to be interferon non-responders.

PMID- 15261566
TI  - Pixantrone (BBR2778): a new immunosuppressant in multiple sclerosis with a low
      cardiotoxicity.
AB  - Mitoxantrone (MX) has been approved by the Food and Drug Administration for the
      treatment of rapidly progressive multiple sclerosis (MS). Unfortunately, its long
      term administration is prevented by the cardiotoxicity. Pixantrone (PIX) is an
      analogue of MX devoid of toxic effects on cardiac tissue and was developed as a
      replacement for other anthracenediones in cancer patients. With a view to an
      application in MS patients, experimental data demonstrated that PIX is as potent
      as MX in preventing acute experimental allergic encephalomyelitis development as
      well as the occurrence of relapses in the chronic model. Safety data from animal
      studies and from phase II trials in cancer patients confirm a very weak
      cardiotoxicity, if any. A phase I trial with PIX in patients with a rapidly
      progressive MS seems thus warranted.

PMID- 15261567
TI  - New immunosuppressants with potential implication in multiple sclerosis.
AB  - New immunosuppressants are consistently developed to treat autoimmune diseases
      and some of them might have implications in multiple sclerosis (MS). A new
      antiproliferative agent, pixantrone, an analogue of mitoxantrone (MX), has a much
      lower cardiotoxicity and exerts the same potent immunosuppressive effects in
      experimental allergic encephalomyelitis (EAE). A phase I trial in MS patients is
      planned in the next future. New monoclonal antibodies (mAb) and other biological
      constructs containing foreign proteins are developed but their potential
      immunogenicity is a considerable drawback to their long-term administration. In
      addition, their beneficial effects in MS are not evident so far. Small molecules
      targeting the voltage-gated Kv1.3K+ channel regulating CA2+ signaling in T
      lymphocytes, specifically target activated, pathogenic T cells. Already found
      effective in EAE, those agents would be easier to handle than T-cell vaccination.
      Two new immunosuppressants with a unique mechanism of action (FTY720 and
      Epomycine M) selectively impair autoreactive T-cell homing, without affecting the
      other components of the immune response. The potent protective effect of TRY720
      has been demonstrated in EAE and a phase I trial in MS appears warranted.
      Finally, a new concept about immunosuppressive treatments in organ
      transplantation, "tolerogenic immunosuppression", may have potential in MS.

PMID- 15261569
TI  - Binding proteins from alternative scaffolds.
AB  - The use of so-called protein scaffolds for the generation of novel binding
      proteins via combinatorial engineering has recently emerged as a powerful
      alternative to natural or recombinant antibodies. This concept requires an
      extraordinary stable protein architecture tolerating multiple substitutions or
      insertions at the primary structural level. With respect to broader applicability
      it should involve a type of polypeptide fold which is observed in differing
      natural contexts and with distinct biochemical functions, so that it is likely to
      be adaptable to novel molecular recognition purposes. The quickly growing number
      of approaches can be classified into three groups: carrier proteins for the
      display of single variegated loops, scaffolds providing rigid elements of
      secondary structure, and protein frameworks supporting a group of
      conformationally variable loops in a fixed spatial arrangement. Generally, such
      artificial receptor proteins should be based on monomeric and small polypeptides
      that are robust, easily engineered, and efficiently produced in inexpensive
      prokaryotic expression systems. Today, progress in protein library technology
      allows for the parallel development of immunoglobulin (Ig) as well as scaffold
      based affinity reagents. Both biomolecular tools have the potential to complement
      each other, thus expanding the possibility to find an affinity reagent suitable
      for a given application. The repertoire of protein scaffolds hitherto recruited
      for combinatorial protein engineering purposes will probably be further expanded
      in the future, including both additional natural proteins and de novo designed
      proteins, contributing to the collection of libraries available at present. In
      this review both the structural features and the practical use of scaffold
      proteins will be discussed and exemplified.

PMID- 15261570
TI  - Antibodies from phage antibody libraries.

PMID- 15261571
TI  - In-vitro protein evolution by ribosome display and mRNA display.
AB  - In-vitro display technologies combine two important advantages for identifying
      and optimizing ligands by evolutionary strategies. First, by obviating the need
      to transform cells in order to generate and select libraries, they allow a much
      higher library diversity. Second, by including PCR as an integral step in the
      procedure, they make PCR-based mutagenesis strategies convenient. The resulting
      iteration between diversification and selection allows true Darwinian protein
      evolution to occur in vitro. We describe two such selection methods, ribosome
      display and mRNA display. In ribosome display, the translated protein remains
      connected to the ribosome and to its encoding mRNA; the resulting ternary complex
      is used for selection. In mRNA display, mRNA is first translated and then
      covalently bonded to the protein it encodes, using puromycin as an adaptor
      molecule. The covalent mRNA-protein adduct is purified from the ribosome and used
      for selection. Successful examples of high-affinity, specific target-binding
      molecules selected by in-vitro display methods include peptides, antibodies,
      enzymes, and engineered scaffolds, such as fibronectin type III domains and
      synthetic ankyrins, which can mimic antibody function.

PMID- 15261572
TI  - Yeast display of antibody fragments: a discovery and characterization platform.
AB  - Yeast display of antibody fragments has proven to be an efficient and productive
      means for directed evolution of single-chain Fv (scFv) antibodies for increased
      affinity and thermal stability and, more recently, for the display and screening
      of a non-immune scFv and immune Fab libraries. A major strength of yeast display
      as a novel antibody discovery platform is the ability to characterize the binding
      properties, i.e., the affinity and epitope binding characteristics, of a clone
      without the need for subcloning, expression and purification of the scFv. This
      review focuses on novel attributes of yeast display for antibody engineering
      endeavors.

PMID- 15261573
TI  - Expression profiling by high-throughput immunohistochemistry.
AB  - Immunohistochemistry (IHC) provides valuable information on expression of
      proteins within tissues at a cellular and subcellular level. Recent developments
      in the practice of IHC now make it possible to contemplate using this technique
      as a high-throughput expression profiling system. Advances have been made in
      creation and use of tissue microarrays, in automated IHC and in image
      capture/analysis. Each of these technologies are reviewed and issues surrounding
      their use considered. The success of high-throughput IHC is also dependent on
      both generation and screening of appropriate antibodies. Antibody-related issues
      which are likely to affect the success of high-throughput IHC, such as
      specificity, sensitivity, fixation choice, etc., are also considered.

PMID- 15261574
TI  - Automated interpretation of subcellular patterns from immunofluorescence
      microscopy.
AB  - Immunofluorescence microscopy is widely used to analyze the subcellular locations
      of proteins, but current approaches rely on visual interpretation of the
      resulting patterns. To facilitate more rapid, objective, and sensitive analysis,
      computer programs have been developed that can identify and compare protein
      subcellular locations from fluorescence microscope images. The basis of these
      programs is a set of features that numerically describe the characteristics of
      protein images. Supervised machine learning methods can be used to learn from the
      features of training images and make predictions of protein location for images
      not used for training. Using image databases covering all major organelles in
      HeLa cells, these programs can achieve over 92% accuracy for two-dimensional (2D)
      images and over 95% for three-dimensional images. Importantly, the programs can
      discriminate proteins that could not be distinguished by visual examination. In
      addition, the features can also be used to rigorously compare two sets of images
      (e.g., images of a protein in the presence and absence of a drug) and to
      automatically select the most typical image from a set. The programs described
      provide an important set of tools for those using fluorescence microscopy to
      study protein location.

PMID- 15261575
TI  - Multiplexed sandwich assays in microarray format.
AB  - Antibody arrays have evolved into powerful tools for quantifying proteins and
      qualifying their state of activation in complex biological samples. This level of
      analysis holds tremendous promise as part of a diagnostic or prognostic platform.
      In particular, multiplex sandwich ELISA assays performed with microarrays in the
      wells of multi-well plates enable high-throughput analysis of multiple samples
      with multivariate readouts. Here, we compare and review recent advances in
      antibody microarray technology and describe its promises towards the systematic
      analysis of complex biological samples, ranging from profiling patient sera to
      studying intracellular signaling.

PMID- 15261576
TI  - Protein microarray detection strategies: focus on direct detection technologies.
AB  - Protein microarrays are being utilized for functional proteomic analysis,
      providing information not obtainable by gene arrays. Microarray technology is
      applicable for studying protein-protein, protein-ligand, kinase activity and
      posttranslational modifications of proteins. A precise and sensitive protein
      microarray, the direct detection or reverse-phase microarray, has been applied to
      ongoing clinical trials at the National Cancer Institute for studying
      phosphorylation events in EGF-receptor-mediated cell signaling pathways. The
      variety of microarray applications allows for multiple, creative microarray
      designs and detection strategies. Herein, we discuss detection strategies and
      challenges for protein microarray technology, focusing on direct detection of
      protein microarrays.

PMID- 15261577
TI  - Intracellular antibodies for proteomics.
AB  - The intracellular antibody technology has many applications for proteomics
      studies. The potential of intracellular antibodies for the systematic study of
      the proteome has been made possible by the development of new experimental
      strategies that allow the selection of antibodies under conditions of
      intracellular expression. The Intracellular Antibody Capture Technology (IACT) is
      an in vivo two-hybrid-based method originally developed for the selection of
      antibodies readily folded for ectopic expression. IACT has been used for the
      rapid and effective identification of novel antigen-antibody pairs in
      intracellular compartments and for the in vivo identification of epitopes
      recognized by selected intracellular antibodies. IACT opens the way to the use of
      intracellular antibody technology for large-scale applications in proteomics. In
      its present format, its use is however somewhat limited by the need of a
      preselection of the input phage antibody libraries on protein antigens or by the
      construction of an antibody library from mice immunized against the target
      protein(s), to provide an enriched input library to compensate for the suboptimal
      efficiency of transformation of the yeast cells. These enrichment steps require
      expressing the corresponding proteins, which represents a severe bottleneck for
      the scaling up of the technology. We describe here the construction of a single
      pot library of intracellular antibodies (SPLINT), a naive library of scFv
      fragments expressed directly in the yeast cytoplasm in a format such that antigen
      specific intrabodies can be isolated directly from gene sequences, with no
      manipulation whatsoever of the corresponding proteins. We describe also the
      isolation from SPLINT of a panel of intrabodies against a number of different
      proteins. The application of SPLINT on a genome-wide scale should help the
      systematic study of the functional organization of cell proteome.

PMID- 15261578
TI  - Syntheses of arabinogalactans consisting of beta-(1-->6)-linked D
      galactopyranosyl backbone and alpha-(1-->3)-linked L-arabinofuranosyl side
      chains.
AB  - Two arabinogalactosyl nonasaccharides, beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->3)]
      beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->5)
      alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp and beta-D-Galp-(1-->6)
      [alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp-(1-
      >6)-beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp,
      were synthesized as their 4-methoxyphenyl glycosides with 2,3,4,6-tetra-O-benzoyl
      alpha-D-galactopyranosyl trichloroacetimidate (1), 6-O-acetyl-2,3,4-tri-O-benzoyl
      alpha-D-galactopyranosyl trichloroacetimidate (14), 4-methoxyphenyl 3-O-allyl-2,4
      di-O-benzoyl-beta-D-galactopyranoside (2), 4-methoxyphenyl 2,3,4-tri-O-benzoyl
      beta-D-galactopyranoside (5), 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl
      trichloroacetimidate (8), and 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl-(1-
      >5)-2,3-di-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (11), as the
      key synthons. The tetra- (10) and pentasaccharide donor (13), and the tetra- (20)
      and pentasaccharide acceptor (22) were synthesized based on these synthons
      through simple transformations. Coupling of 22 with 10, and coupling of 20 with
      13 and subsequent deacylation gave nonasaccharides 24 and 26, respectively,
      consisting of beta-(1-->6)-linked glactopyranosyl backbone and alpha-(1-->3)
      linked arabinofuranosyl side chains of different size.

PMID- 15261579
TI  - Enzyme-catalysed synthesis of galactosylated 1D- and 1L-chiro-inositol, 1D
      pinitol, myo-inositol and selected derivatives using the beta-galactosidase from
      the thermophile Thermoanaerobacter sp. strain TP6-B1.
AB  - The products from the enzymatic beta-D-galactopyranosylation of 1D-chiro
      inositol, 1D-pinitol, 1D-3-O-allyl-4-O-methyl-chiro-inositol, 1D-3,4-di-O-methyl
      chiro-inositol, 1L-chiro-inositol and myo-inositol in combined yields ranging
      from 46% to 64% have been obtained using the beta-galactosidase isolated from an
      anaerobic extreme thermophile, Thermoanaerobacter sp. strain TP6-B1 and p
      nitrophenyl beta-D-galactopyranoside as the donor. Analysis of the products from
      these reactions reveals information about the acceptor preferences of the enzyme.

PMID- 15261580
TI  - Synthesis of a glucuronic acid and glucose conjugate library and evaluation of
      effects on endothelial cell growth.
AB  - Compounds that alter endothelial cell growth are of interest in the development
      of angiogenesis modulators. A structurally diverse series of saccharide
      derivatives (glycosylamide conjugates) have been synthesized and evaluated for
      their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin
      (HA) reduced BAEC growth by 32% at 10 microg/mL and a number of the novel
      saccharide conjugates from the library were found to mimic the effect of HA as
      they also inhibit endothelial cell survival under identical conditions. Two
      thiophene conjugates, thioglucamide (24% inhibition at 35 microM) and a related
      glucuronide (26% inhibition at 33 microM) were the most potent inhibitors of BAEC
      growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects
      of thioglucamide and HA on absolute cell number were also studied using cell
      counting experiments; thioglucamide (47% after 24 h) was more potent than
      indicated by the MTT assay and initially reduced the BAEC number to a greater
      extent than HA (30% after 24 h); however, its actions were over more rapidly than
      were HA's as cell growth had returned to levels of the control after 72 h where
      HA still caused 25% inhibition. The binding of the monosaccharide conjugates to
      fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was
      investigated to establish the possible mechanism by which glycoconjugates could
      alter growth but there was no general correlation between reduction in viable
      cell population and binding to FGF-2. No glycoconjugate reduced the proliferation
      of mouse mammary epithelial cells, nor did any alter gross cell morphology,
      supporting a proposal that the reduction in BAEC survival by monosaccharide
      conjugates such as thioglucamide is a result of the inhibition of cell
      proliferation rather than being an induction of cytotoxicity. These studies
      indicate that cell biological studies to determine the mechanism of action of the
      simple monosaccharide conjugates may be worthwhile.

PMID- 15261581
TI  - Sugar bislactones by one-step oxidative dimerisation with pyridinium
      chlorochromate versus regioselective oxidation of vicinal diols.
AB  - Synthesis of 10-membered bislactones by PCC oxidation of methyl 2,6-di-O-pivaloyl
      alpha-D-glucopyranoside and methyl 4,6-O-benzylidene-alpha-D-glucopyranoside is
      described, with emphasis on their structure elucidation using the information
      gained by combination of NMR spectroscopic techniques with X-ray diffraction
      data. In alternative, the use of PCC and PCC adsorbed on silica gel or alumina
      for the regioselective oxidation of vicinal diols in sugars is also reported.
      Both bislactones showed antifungal activity against Candida albicans, and were
      slightly active against the bacteria Bacillus subtilis. The bislactone presenting
      pivaloyl protecting groups also promoted some growth inhibition of Staphylococcus
      aureus.

PMID- 15261583
TI  - Synthesis of a D-rhamnose branched tetrasaccharide, repeating unit of the O-chain
      from Pseudomonas syringae pv. Syringae (cerasi) 435.
AB  - The first synthesis of a d-rhamnose branched tetrasaccharide, corresponding to
      the repeating unit of the O-chain from Pseudomonas syringae pv. cerasi 435, as
      methyl glycoside is reported. The approach used is based on the synthesis of an
      opportune building-block, that is the methyl 3-O-allyl-4-O-benzoyl-alpha-D
      rhamnopyranoside, which was then converted into both a glycosyl acceptor and two
      different protected glycosyl trichloroacetimidate donors. Successive couplings of
      these three compounds afforded the target oligosaccharide. The reported synthesis
      is also useful to perform the oligomerization of the repeating unit.

PMID- 15261582
TI  - Kinetic and chemical studies on the isomerization of monosaccharides in N
      methylmorpholine-N-oxide (NMMO) under Lyocell conditions.
AB  - The Lyocell process is a modern and environmentally fully compatible industrial
      fiber-making technology. Cellulosic pulp is dissolved without chemical
      derivatization in a melt of N-methylmorpholine-N-oxide monohydrate (NMMO). In the
      present work, the reactions of monosaccharides under Lyocell conditions were
      investigated in detail, using capillary zone electrophoresis as the analytical
      technique to clarify the composition of reaction mixtures and to follow the
      kinetics. Under Lyocell conditions, xylose and glucose undergo two competitive
      reactions: rapid conversion to nonreducing products, and complete isomerization
      involving the whole carbohydrate backbone, via ketose intermediates. Sugar acids
      are present in minor amounts only, as demonstrated by employing isotopically
      labeled material for NMR techniques.

PMID- 15261584
TI  - Determination of the degree of substitution and its distribution of
      carboxymethylcelluloses by capillary zone electrophoresis.
AB  - A method based on capillary zone electrophoresis (CZE) has been developed to
      determine the degree of substitution (DS) of carboxymethylcellulose (CMC).
      Separations were performed with borate buffer (pH 9, ionic strength 20 mM) as
      background electrolyte in capillaries of 75 microm ID, with an applied voltage of
      10 kV, and for detection UV absorption at 196 nm was measured. The use of an
      internal standard (phthalic acid) to correct for mobility variations resulted in
      a strong improvement of the precision of the DS determination. Experiments with
      indirect UV detection indicated that the peak widths obtained actually reflect
      the variation in mobility, and with that of the DS value, of CMC samples. With
      the proposed method not only the average DS value but also its dispersity could
      be established for technical CMC samples. A small but definite effect of the
      polymeric size on the mobilities was observed. Therefore, DS calibration curves
      will have to be determined for a specific MM range. Since the size effect is
      small, a classification of CMCs as low-, middle-, or high MM will be sufficient
      to obtain accurate data on the DS distribution.

PMID- 15261585
TI  - Synthesis and characterization of camphorsulfonyl acetate of cellulose.
AB  - Novel cellulose derivatives were prepared from reacting (1R)-(+)-camphor-10
      sulfonic chloride (CSC) with cellulose acetate (CA) in acetone and triethylamine.
      The reaction conditions, including reaction time and reactant molar ratios, were
      optimized. The structure of the products was confirmed by means of 1H NMR, 13C
      NMR, FT-IR and elementary analysis. The techniques were also used to determine
      the degree of the substitution of camphorsulfonyl groups (DSCS). The data
      calculated from 1H NMR, 13C NMR, percent grafting (G %) and elementary analysis
      coincided with those from chemical analysis. Compared to cellulose acetate, the
      cellulose derivatives exhibited decreased thermal stability, improved solubility
      in organic solvents and enhanced enantioselectivity towards tyrosine isomers. The
      solubility and enantioselectivity increased with increasing degrees of
      camphorsulfonyl substitution.

PMID- 15261586
TI  - Pectin-chitosan interactions and gel formation.
AB  - The effect of chitosan concentration on the gelation of pectins differing in
      charge density and distribution was examined, through the determination of gel
      stiffness and the binding of chitosan to the gel network. Chitosan acts as a
      crosslinker of concentrated pectin solutions, with its effectiveness showing a
      dependency on charge on the pectin. The networks produced are clear even under
      conditions of charge neutralisation.

PMID- 15261587
TI  - Binuclear copper(II) complexes of 5-N-(beta-ketoen)amino-5-deoxy-1,2-O
      isopropylidene-alpha-D-glucofuranoses: synthesis, structure, and catecholoxidase
      activity.
AB  - The synthesis of 5-amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose (8)
      was carried out via 5-azido-5-deoxy-1,2:3,4-O-diisopropylidene-alpha-D
      glucofuranose (6), its reduction with Raney-Nickel and deprotection. 5-N-(beta
      Ketoen)amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranoses (8a-f) were
      synthesized from 5-amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose and
      beta-ketoenolethers leading to ligands with symmetrically substituted double
      bonds (8a, 8b) and e/z isomeric mixtures with unsymmetrical substitution (8c-f).
      Reaction of the ligands with Cu(II) ions leads to binuclear complexes of the
      general formula Cu2L2. In contrast to copper(II) complexes which are not derived
      from amino carbohydrates the metal centers in the compounds saturate their
      coordination sphere by complexation of additional solvent molecules, interaction
      with neighboring complex molecules, or free hydroxyl groups of the own ligand.
      Residues of the ketoen moiety, R1 and R2, also influence the electronic
      properties of the metal centers. The combination of factors leads to different
      catalytic properties of the complexes in catecholoxidase-like reactions.

PMID- 15261588
TI  - The conformational free-energy map for solvated neocarrabiose.
AB  - A Ramachandran map of the conformational potential of mean force (pmf) for
      neocarrabiose in water was obtained using molecular dynamics (MD) simulations
      with umbrella sampling. The potential energy map calculated in a previous study
      for this molecule in vacuum exhibited a global minimum located at (phi = 81
      degrees, psi = -141 degrees). However, the global minimum on the new pmf map in
      aqueous solution is located in an area centered around (phi = 175 degrees, psi =
      180 degrees), indicating a considerable solvent shift. This new global minimum
      energy solution conformation was found to correspond to the experimental value
      obtained from NMR-NOE measurements, and is also consistent with the experimental
      crystal structure for neocarrabiose and the fiber diffraction conformation for
      iota-carrageenan. The global minimum of the solution pmf and its local topology
      were found to be approximately reproduced by quick vacuum conformational energy
      mapping using several approximations that mimic solvation effects by de
      emphasizing intramolecular hydrogen bonding.

PMID- 15261589
TI  - Molecular dynamics (MD) simulations for the prediction of chiral discrimination
      of N-acetylphenylalanine enantiomers by cyclomaltoheptaose (beta-cyclodextrin,
      beta-CD) based on the MM-PBSA (molecular mechanics-Poisson-Boltzmann surface
      area) approach.
AB  - Molecular dynamics (MD) simulations were performed for the prediction of chiral
      discrimination of N-acetylphenylalanine enantiomers by cyclomaltoheptaose (beta
      cyclodextrin, beta-CD). Binding free energies and various conformational
      properties were obtained using by the MM-PBSA (molecular mechanics Poisson
      Boltzmann/surface area) approach. The calculated relative difference
      (DeltaDeltabinding) of binding free energy was in fine agreement with the
      experimentally determined value. The difference of rotameric distributions of
      guest N-acetylphenylalanine enantiomers complexed with the host, beta-CD, was
      observed after the conformational analyses, suggesting that the conformational
      changes of guest captured within host cavity would be a decisive factor for
      enantiodifferentiation at a molecular level.

PMID- 15261590
TI  - Carbohydrates from Cynanchum otophyllum.
AB  - Four new carbohydrates were isolated from the acidic hydrolysis part of the ethyl
      acetate extract of Cynanchum otophyllum Schneid (Asclepiadaceae). Their
      structures were determined as methyl 2,6-dideoxy-3-O-methyl-beta-D-arabino
      hexopyranosyl-(1-->4)-6-deoxy-3-O-methyl-beta-D-ribo-hexopyranosyl-(1-->4)-6
      deoxy-3-O-methyl-alpha-L-ribo-hexopyranoside (1), methyl 6-deoxy-1,3-di-O-methyl
      beta-D-ribo-hexosyl-(1-->4)-2,6-dideoxy-3-O-methyl-alpha-D-arabino-hexopyranoside
      (2), methyl 2,6-dideoxy-3-O-methyl-beta-D-arabino-hexopyranosyl-(1-->4)-6-deoxy-3
      O-methyl-alpha-L-ribo-hexopyranoside (3), and 2,6-dideoxy-3-O-methyl-beta-D
      arabino-hexopyranosyl-(1-->4)-2,6-dideoxy-3-O-methyl-alpha-D-arabino
      hexopyranosyl-(1-->4)-2,6-dideoxy-3-O-methyl-beta-D-lyxo-hexopyranose (4),
      respectively, by spectral methods.

PMID- 15261591
TI  - Structural analysis of the lipopolysaccharide derived core oligosaccharides of
      Actinobacillus pleuropneumoniae serotypes 1, 2, 5a and the genome strain 5b.
AB  - The structures of the core oligosaccharides of the lipopolysaccharides (LPS) from
      Actinobacillus pleuropneumoniae serotypes 1, 2, 5a and 5b were elucidated. The
      LPS's were subjected to a variety of degradative procedures. The structures of
      the purified products were established by monosaccharide and methylation
      analyses, NMR spectroscopy and mass spectrometry. The following structures for
      the core oligosaccharides were determined on the basis of the combined data from
      these experiments. [carbohydrate formula see text] For serotype 1: R is (1S)
      GalaNAc-(1-->4,6)-alpha-Gal II-(1-->3)-beta-Gal I-(1-->, and R' is H For serotype
      2: R is beta-Glc III-(1-->, and R' is D-alpha-D-Hep V-(1--> For serotypes 5a and
      5b: R is H and R' is D-alpha-D-Hep V-(1--> All oligosaccharides elaborated a
      conserved inner core structure, as illustrated. All sugars were in the pyranose
      ring form apart from the open-chain N-acetylgalactosamine, the identification of
      which in the serotype 1 LPS was of interest.

PMID- 15261592
TI  - The complete structure of the lipooligosaccharide from the halophilic bacterium
      Pseudoalteromonas issachenkonii KMM 3549T.
AB  - Novel lipooligosaccharide components were isolated and identified from the
      lipooligosaccharide fraction of the halophilic marine bacterium Pseudoalteromonas
      issachenkonii type strain KMM 3549T. The complete structure was achieved by
      chemical analysis, 2D NMR spectroscopy and MALDI mass spectrometry as the
      following: [carbohydrate formula see text] All sugars are d-pyranoses. Hep is L
      glycero-D-manno-heptose, Kdo is 3-deoxy-D-manno-oct-2-ulosonic acid, P is
      phosphate, residues and substituents in italic are not stoichiometrically linked.
      In addition, by MALDI mass spectrometry of the intact LOS, the lipid A moiety was
      also identified as a mixture of penta-, tetra- and triacylated species.

PMID- 15261593
TI  - Crystal structures of dihydroxyacetone and its derivatives.
AB  - The crystal and molecular structures of three crystalline forms of the
      dihydroxyacetone dimer, C6H12O6, DHA-dimer: alpha (1a), beta (1b), and gamma
      (1c), the hydrated calcium chloride complex of dihydroxyacetone monomer,
      CaCl2(C3H6O3)(2) x H2O, CaCl2(DHA)2 x H2O (2a), the tetrahydrated calcium
      chloride complex of dihydroxyacetone monomer, CaCl2(C3H6O3) x 4H2O, CaCl2(DHA) x
      4H2O (2b), the dihydroxyacetone monomer, C3H6O3, DHA (2c), and dihydroxyacetone
      dimethyl acetal, C5H12O4, (MeO)2DHA (3) are described. Compounds 1a and 2b
      crystallize in the triclinic system, and 1b,c, 2a,c, and 3 are monoclinic.
      Molecules of all forms of dihydroxyacetone dimer 1a,b, and 1c are the trans
      isomers, with the 1,4-dioxane ring in the chair conformation and the hydroxyl and
      hydroxymethyl groups in axial and equatorial dispositions, respectively. The Ca2+
      ions in 2a and 2b are bridged by the carbonyl O atoms from two symmetry-related
      DHA molecules to form centrosymmetric dimers with Ca...Ca distance of 4.307(2)A
      in 2a and 4.330(2) and 4.305(2)A in two crystallographically independent dimers
      in 2b. DHA molecules coordinate to the Ca2+ ions by hydroxyl and carbonyl oxygen
      atoms. The eight-coordinate polyhedra of Ca2+ are completed by water molecule and
      Cl- ion in 2a and by four water molecules in 2b. The dihydroxyacetone molecules
      in 2a,b, and 2c are in an extended conformation, with both hydroxyl groups being
      synperiplanar (sp) to the carbonyl O atom. All hydroxyl groups in 2c (along with
      water molecules in 2a and 2b) are involved as donors in medium strong and weak
      intermolecular O-H...O hydrogen bonding. Some of them, as well as carbonyl O
      atoms or Cl- ions in 2a and 2b, act as acceptors in C-H...O (and C-H...Cl)
      hydrogen interactions.

PMID- 15261594
TI  - The gel-forming polysaccharide of psyllium husk (Plantago ovata Forsk).
AB  - The physiologically active, gel-forming fraction of the alkali-extractable
      polysaccharides of Plantago ovata Forsk seed husk (psyllium seed) and some
      derived partial hydrolysis products were studied by compositional and methylation
      analysis and NMR spectroscopy. Resolving the conflicting claims of previous
      investigators, the material was found to be a neutral arabinoxylan (arabinose
      22.6%, xylose 74.6%, molar basis; only traces of other sugars). With about 35% of
      nonreducing terminal residues, the polysaccharide is highly branched. The data
      are compatible with a structure consisting of a densely substituted main chain of
      beta-(1-->4)-linked D-xylopyranosyl residues, some carrying single xylopyranosyl
      side chains at position 2, others bearing, at position 3, trisaccharide branches
      having the sequence L-Araf-alpha-(1-->3)-D-Xylp-beta-(1-->3)-l-Araf. The presence
      of this sequence is supported by methylation and NMR data, and by the isolation
      of the disaccharide 3-O-beta-D-xylopyranosyl-L-arabinose as a product of partial
      acid hydrolysis of the polysaccharide.

PMID- 15261595
TI  - Synthesis of pentose-containing disaccharides using a thermostable alpha-L
      arabinofuranosidase.
AB  - To date, the enzymatically-catalysed synthesis of pentose-containing compounds
      has been limited to the production of oligo-beta-(1-->3) and oligo-beta-(1-->4)
      linked xylopyranosides. To our knowledge, no such syntheses have involved
      arabinofuranose or, indeed, any other sugars in the furanose configuration. In
      this report, we describe the use of a thermostable alpha-L-arabinofuranosidase
      for the synthesis of p-nitrophenyl alpha-L-arabinofuranosyl-(1-->2)-alpha-L
      arabinofuranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->2)-beta-D
      xylopyranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranoside
      and benzyl alpha-D-xylopyranosyl-(1-->2)-alpha-L-arabinofuranoside. Importantly,
      this latter compound is synthesised in a highly regiospecific reaction, which
      leads to the production of a single disaccharide.

PMID- 15261596
TI  - Determination of the structures of four new isomeric cyclitols.
AB  - A series of impurities, which were all of the same molecular formula, C17H33NO7,
      were obtained in the process of voglibose synthesis. After isolation and
      purification, four isomeric cyclitols were completely assigned by 2D NMR
      experiments. One of the compounds was established by single-crystal X-ray
      diffraction analysis as 5,6-dideoxy-5-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-1
      C-(methoxycyclohexylmethyl)-D-epi-inositol.

PMID- 15261597
TI  - Reinvestigation of the mercuration-demercuration reaction on alkylated glycals:
      an improved method for the preparation of 2,3-dideoxy-alpha,beta-unsaturated
      carbohydrate enals.
AB  - Alkyl protected glycals can be easily converted into their corresponding
      alpha,beta-unsaturated enals (Perlin aldehydes) in good to very good yields by
      reaction with HgSO4 and aqueous 0.02 N H2SO4 in THF or 1,4-dioxane. While the
      formation of Perlin aldehydes from benzyl-protected glucal and arabinal was
      accomplished by refluxing the reaction mixture in 1,4-dioxane, the benzyl
      protected galactal and methyl-protected glucal, galactal, and arabinal yielded
      aldehydes from this reaction at room temperature using THF or 1,4-dioxane as
      solvent.

PMID- 15261598
TI  - An optimized CZE method for analysis of mono- and oligomeric aldose mixtures.
AB  - An optimized capillary electrophoresis (CZE) method to analyze complex mixtures
      of aldoses was developed. The approach allows simultaneous quantitative analysis
      of all four isomeric aldopentoses, eight aldohexoses, as well as xylo- and
      cellooligosaccharides up to the tetraoses. UV tagging with 4-aminobenzoic acid
      ethyl ester (ABEE) in combination with reductive amination was used as pre-column
      derivatization. With optimum baseline separation and short run times, the method
      is very robust, and especially suited to follow reaction and isomerization
      kinetics of monosaccharides.

PMID- 15261599
TI  - The structure of the O-specific polysaccharide from Ralstonia pickettii.
AB  - The following structure of the Ralstonia pickettii have been determined using NMR
      and chemical methods: -->4)-alpha-D-Rha-(1-->4)-alpha-L-GalNAcA-(1-->3)-beta-D
      BacNAc-(1-->.

PMID- 15261600
TI  - Structure and hydrodynamic properties of the extracellular polysaccharide from a
      mutant strain (RA3W) of Erwinia chrysanthemi RA3.
AB  - The structure of the extracellular polysaccharide (EPS) produced by Erwinia
      chrysanthemi strain RA3W, a mutant strain of E. chrysanthemi RA3, has been
      determined using low pressure size-exclusion and anion-exchange chromatographies,
      high pH anion-exchange chromatography, glycosyl linkage analysis, and 1D 1H NMR
      spectroscopy. The polysaccharide is structurally similar, if not identical, to
      the family of EPS produced by such as E. chrysanthemi strains Ech9, Ech9Sm6, and
      SR260. The molecular weight of EPS RA3W by ultracentrifugation (sedimentation
      equilibrium) and light scattering is compared with those of other E. chrysanthami
      EPSs, as are the viscometric properties.

PMID- 15261601
TI  - Clinical trial database: carrot or stick?

PMID- 15261602
TI  - Carotid surgery to prevent stroke.

PMID- 15261603
TI  - Oral contraceptives and stroke risk: the debate continues.

PMID- 15261604
TI  - Closed doors and false expectations: cell-based therapies for PD.

PMID- 15261605
TI  - Dementia in Parkinson's disease: common and treatable.

PMID- 15261607
TI  - Neuroprotection and pharmacotherapy for motor symptoms in Parkinson's disease.
AB  - Parkinson's disease leads to major disability that impairs the quality of life of
      patients and leads to increased health-care costs. While there is no proven
      neuroprotective treatment, more basic-science research and clinical trials are
      needed to identify drugs that slow or halt the progression of the disorder. The
      mainstay of symptomatic treatment is levodopa. With long-term use, levodopa
      causes motor complications including involuntary movements and response
      fluctuations. These have lead to more cautious prescribing of levodopa. Dopamine
      agonists can be used as an alternative initial therapy to delay the onset of
      motor complications but at the expense of more dopaminergic adverse events,
      poorer control of motor symptoms, and increased cost. Once motor complications
      have developed, adjuvant therapy with dopamine agonists or entacapone can reduce
      off time and levodopa dose. Severe fluctuations that are not controlled by oral
      combination therapy can be controlled with subcutaneous apomorphine injections or
      infusions.

PMID- 15261606
TI  - Immune-mediated components of hereditary demyelinating neuropathies: lessons from
      animal models and patients.
AB  - Most demyelinating forms of Charcot-Marie-Tooth type 1 (CMT1) neuropathy are
      slowly progressive and do not respond to anti-inflammatory treatment. In nerve
      biopsy samples, overt lymphocytic infiltration is absent, but pathological
      features typical of macrophage-related demyelination have been reported. In mouse
      models of CMT1, demyelination was substantially reduced when the mutants were
      backcrossed into an immunodeficient genetic background. A few individual patients
      with CMT1 respond to anti-inflammatory treatment; however, unlike most patients
      with CMT1, these patients show accelerated worsening of symptoms, inflammatory
      infiltrates in nerve biopsies, and clinical features resembling chronic
      inflammatory demyelinating polyneuropathy as well as CMT1. We conclude that in
      patients with typical CMT1 and in animal models, a cryptic and mild inflammatory
      process not responsive to standard anti-inflammatory treatment fosters
      genetically mediated demyelination.

PMID- 15261608
TI  - Medication-overuse headache: a worldwide problem.
AB  - Medication overuse and subsequent medication-overuse headache (MOH) is a growing
      problem worldwide. Epidemiological data suggest that up to 4% of the population
      overuse analgesics and other drugs for the treatment of pain conditions such as
      migraine and that about 1% of the general population in Europe, North America,
      and Asia have MOH. Recent clinical studies gave further insights in clinical and
      pharmacological features, such as critical monthly doses and frequencies. These
      features seem to vary significantly and depend on the primary headache disorder
      and the type of drug that is overused. Along with these findings the new
      international classification of headache disorders has now incorporated
      additional criteria and new headache entities that will facilitate the diagnosis
      of MOH. Withdrawal therapy is the only treatment for this disorder and clear
      restriction of monthly doses is the central requirement for successful
      prevention.

PMID- 15261609
TI  - Cerebral amyloid angiopathy and thrombolysis-related intracerebral haemorrhage.
AB  - Intracerebral haemorrhage is a complication of thrombolytic therapy for acute
      myocardial infarction, pulmonary embolism, and ischaemic stroke. There is
      increasing evidence that cerebral amyloid angiopathy (CAA), which itself can
      cause haemorrhage (CAAH), may be a risk factor for thrombolysis-related
      intracerebral haemorrhage. CAAH and thrombolysis-related intracerebral
      haemorrhage share some clinical features, such as predisposition to lobar or
      superficial regions of the brain, multiple haemorrhages, increasing frequency
      with age, and an association with dementia. In vitro work showed that
      accumulation of amyloid-beta peptide causes degeneration of cells in the walls of
      blood vessels, affects vasoactivity, and improves proteolytic mechanisms, such as
      fibrinolysis, anticoagulation, and degradation of the extracellular matrix. In a
      mouse model of CAA there is a low haemorrhagic threshold after thrombolytic
      therapy compared with that in wild-type mice. To date only a small number of
      anecdotal clinicopathological relations have been reported; neuroimaging advances
      and further study of the frequency and role of CAA in patients with thrombolysis
      related intracerebral haemorrhage are required.

PMID- 15261610
TI  - Homocysteine, B-vitamin supplementation, and stroke prevention: from
      observational to interventional trials.
AB  - BACKGROUND: Homocysteine is an amino acid, the metabolism of which is linked to
      that of several vitamins-especially folic acid, B6, and B12. A high concentration
      of homocysteine in the plasma is linked to vascular disease, including stroke.
      Concentrations of homocysteine can be inexpensively and safely lowered by
      treatment with a combination of folate, vitamin B12, and vitamin B6. However,
      whether the association between high plasma concentrations of homocysteine and
      vascular disease is causal is unclear. RECENT DEVELOPMENTS: Two studies have
      assessed the relation between dietary or supplementary B vitamin intake on the
      risk of stroke. In a prospective observational study of 43?732 healthy men, there
      was an inverse relation between dietary folate intake and the risk of ischaemic
      stroke. The Vitamin Intervention for Stroke Prevention study (VISP) was the first
      large-scale randomised interventional study that investigated the lowering of
      homocysteine concentrations with B vitamins in patients with ischaemic stroke.
      There was an association between baseline homocysteine concentrations and
      vascular risk in this trial. Plasma concentrations of homocysteine were only
      modestly reduced by high-dose versus low-dose formulation, and there was no
      treatment effect on recurrent stroke, coronary events, or deaths. Limitations of
      VISP included that only patients with mild increases in baseline homocysteine
      concentrations were studied, only modest reductions of homocysteine
      concentrations were achieved, and follow up was short. In addition, fortification
      of food with folate and treatment of low vitamin-B12 concentrations may have
      masked the effect of treatment on stroke risk. WHAT NEXT?: When exposure can be
      safely assigned at random, as in the case of B-vitamin therapy, randomised trials
      should be the standard proof to determine the effect of therapy. The results of
      the first randomised clinical trial of B vitamins for secondary prevention of
      stroke were neutral. Larger trials with longer follow-up, selection of patients
      with higher plasma concentrations of homocysteine, and systematic assessment of
      cognitive functions and dementia are needed. In the meantime, homocysteine
      lowering treatment that is cheap and well-tolerated should be considered a
      rational approach in patients at high risk of stroke and high concentrations of
      homocysteine.

PMID- 15261611
TI  - Lewy-body formation is an aggresome-related process: a hypothesis.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative disorder that is
      associated with the formation of intracytoplasmic protein aggregates (Lewy-body
      inclusions) in neurons of the substantia nigra pars compacta and other brain
      areas. These inclusions were discovered over 90 years ago, but the mechanism
      underlying their formation and their relevance to the neurodegenerative process
      are unknown. Recent studies have begun to shed light on the biogenesis of Lewy
      bodies and suggest that they are related to aggresomes. Aggresomes are
      cytoprotective proteinaceous inclusions formed at the centrosome that segregate
      and facilitate the degradation of excess amounts of unwanted and possibly
      cytotoxic proteins. The concept of Lewy bodies as aggresome-related inclusions
      fits well with ongoing discoveries suggesting that altered protein handling might
      contribute to the neurodegenerative process in familial and sporadic forms of PD.

PMID- 15261612
TI  - A roving eye.

PMID- 15261613
TI  - Reduction of wave phenomena in high-field MRI experiments using absorbing layers.
AB  - Wave behavior, such as constructive and destructive interference, can decrease RF
      field homogeneity. As the static magnetic field strengths increase, these effects
      become more significant, resulting in image inhomogeneities. For a surface coil,
      wave interference is due to reflections at boundaries separating regions with
      largely different dielectric constants. An approach is presented to eliminate
      wave reflections through the use of absorbing layers. A one-dimensional plane
      wave model and a three-dimensional finite difference time domain numerical model
      at 470 MHz are presented validating the theoretical effectiveness of the
      approach. The findings are verified experimentally with 1 H MRI on phantoms at
      11.1 T, demonstrating greatly reduced interference patterns in the images.

PMID- 15261614
TI  - Feasibility of diffusion-NMR surface-to-volume measurements tested by
      calculations and computer simulations.
AB  - It has been demonstrated previously that the surface-to-volume ratio S/V can be
      determined from the derivative of the time-dependent diffusion coefficient D(t),
      in the limit t --> 0. Several questions arise concerning the practicality of
      determining S/V by NMR. In particular, how large are the errors generated by (1)
      working outside the t --> 0 limit and (2) measuring D outside the b --> 0 limit,
      both for narrow and full-width gradient pulses? Here b is gamma2G2delta2Delta for
      narrow pulses and gamma2G2t3/12 for broad pulses. These questions are addressed
      by random-walk computer simulations and numerical calculations in geometries
      relevant to small-airways of lung. The results demonstrate that one can work well
      outside the t --> 0 and b --> 0 limits, provided 10-20% accuracy in the measured
      S/V is sufficient. Emphasis is placed on the useful range of times t for which
      NMR determinations of lung S/V are feasible.

PMID- 15261615
TI  - NMR relaxation and pulsed field gradient study of alginate bead porous media.
AB  - Experiments are presented, which correlate molecular displacement with the multi
      exponential T2 relaxation times of water flowing and diffusing through an
      alginate bead pack. Three systems were studied comprising beads of 3, 1 or < mm
      in diameter. T2-resolved propagators were obtained through a combined pulsed
      gradient stimulated echo (PGSTE) and Carr-Purcell-Meiboom-Gill (CPMG) experiment.
      Fourier transformation with respect to q produces a propagator for each echo in
      the CPMG train. Inverse Laplace transformation of the CPMG decays for each point
      (Z) in the propagator produced a two-dimensional propagator. Analysis of these
      two-dimensional propagators provided insight into the transport and exchange
      behaviour of water flowing through this system. This experiment has been
      simulated in a model bead structure and the resulting T2 relaxation time
      behaviour and T2-resolved propagators were found to be in good agreement with the
      experimental data. We also present a theoretical analysis of the response to the
      combined PGSTE/CPMG sequence in the simple model case of Pouseille flow in a
      cylindrical capillary, where diffusion to a surface sink is assumed to be the
      dominant relaxation mechanism.

PMID- 15261617
TI  - Simple modeling of dipolar coupled 7Li spins and stimulated-echo spectroscopy of
      single-crystalline beta-eucryptite.
AB  - Stimulated-echo spectroscopy has recently been applied to study the ultra-slow
      dynamics of nuclear spin-3/2 probes such as 7Li and 9Be in solids. Apart from the
      dominant first-order quadrupolar interaction in the present article also the
      impact of the homonuclear dipolar interactions is considered in a simple way: the
      time evolution of a dipole coupled pair of spins with I = 3/2 is calculated in an
      approximation, which takes into account that the satellite transitions usually do
      not overlap. Explicit analytical expressions describing various aspects of a
      coupled quadrupolar pair subjected to a Jeener-Broekaert pulse sequence are
      derived. Extensions to larger spin systems are also briefly discussed. These
      results are compared with experimental data on a single-crystalline Li ion
      conductor.

PMID- 15261616
TI  - Ultra-high resolution 3D NMR spectra from limited-size data sets.
AB  - The advantage of the filter diagonalization method (FDM) for analysis of triple
      resonance NMR experiments is demonstrated by application to a 3D constant time
      (CT) HNCO experiment. With a 15N-,13C-labeled human ubiquitin sample (1.0 mM),
      high spectral resolution was obtained at 500 MHz in 25 min with only 6-8
      increments in each of the CT dimensions. This data set size is about a factor of
      50-100 smaller than typically required, yet FDM analysis results in a fully
      resolved spectrum with a sharp peak for each HNCO resonance. Unlike Fourier
      transform (FT) processing, in which spectral resolution in each dimension is
      inversely proportional to the acquisition time in this dimension, FDM is a true
      multi-dimensional method; the resolution in all dimensions is determined by the
      total information content of the entire signal. As the CT dimensions of the 3D
      HNCO signal have approximate time-reversal symmetry, they can each be doubled by
      combining the usual four hyper-complex data sets. This apparent quadrupling of
      the data is important to the success of the method. Thus, whenever raw
      sensitivity is not limiting, well-resolved n-dimensional spectra can now be
      obtained in a small fraction of the usual time. Alternatively, to maximize
      sensitivity, evolution periods of faster relaxing nuclei may be radically
      shortened, the total required resolution being obtained through chemical shift
      encoding of other, more slowly relaxing, spins. Improvements similar to those
      illustrated with a 3D HNCO spectrum are expected for other triple-resonance
      spectra, where CT evolution in the indirect dimensions is implemented.

PMID- 15261618
TI  - Multiple quantum inversion in scalar coupled systems with amplitude modulated
      temporally overlapped pulses.
AB  - In this paper we propose the extension of stimulated Raman adiabatic passage, a
      popular technique in optics for population inversion in three-level systems, to
      the NMR regime. The technique employs two amplitude modulated pulses-the first
      connecting the final and intermediate states followed by a second partially
      overlapped in time with it and connecting the ground and intermediate states. We
      present computer simulations demonstrating the applicability of the technique in
      NMR although we are no longer dealing with "pure" states, unlike in optics.
      Double quantum population inversion in two- and three-spin scalar coupled systems
      provides experimental support to our proposal.

PMID- 15261619
TI  - meta-DENSE complex acquisition for reduced intravoxel dephasing.
AB  - Displacement encoding with stimulated echoes (DENSE) with a meta-DENSE readout
      and RF phase cycling to suppress the STEAM anti-echo is described for reducing
      intravoxel dephasing signal loss. This RF phase cycling scheme, when combined
      with existing meta-DENSE suppression of the T1 recovering signal, yields higher
      quality DENSE myocardial strain maps. Phantom and human images are provided to
      demonstrate the technique, which is capable of acquiring phase contrast
      displacement encoded images at low encoding gradient strengths providing better
      spatial resolution and less signal loss due to intravoxel dephasing than prior
      methods.

PMID- 15261620
TI  - Nanoscale NMR velocimetry by means of slowly diffusing tracer particles.
AB  - The resolution of NMR velocimetry is inherently limited by random displacements
      due to molecular self-diffusion, and has so far not extended below a few tens of
      microns. We report here an extension to the nanoscale domain, a result achieved
      by the use of slowly diffusing, NMR-visible core-shell latex particles. These
      particles comprise an oil core surrounded by a solid polymer shell, making
      spheres of diameter 370 nm. Using these particles in the annulus of a concentric
      cylinder Couette cell, we have measured flow-induced displacements down to a few
      hundreds of nanometers, allowing the observation of the solid-to-liquid
      transition of a glassy system. We envisage new possibilities for NMR velocimetry
      as an experimental tool for colloidal chemistry and physics.

PMID- 15261621
TI  - Improved DOSY NMR data processing by data enhancement and combination of
      multivariate curve resolution with non-linear least square fitting.
AB  - The quality of DOSY NMR data can be improved by careful pre-processing
      techniques. Baseline drift, peak shift, and phase shift commonly exist in real
      world DOSY NMR data. These phenomena seriously hinder the data analysis and
      should be removed as much as possible. In this paper, a series of preprocessing
      operations are proposed so that the subsequent multivariate curve resolution can
      yield optimal results. First, the baseline is corrected according to a method by
      Golotvin and Williams. Next, frequency and phase shift are removed by a new
      combination of reference deconvolution (FIDDLE), and a method presented by Witjes
      et al. that can correct several spectra simultaneously. The corrected data are
      analysed by the combination of multivariate curve resolution with non-linear
      least square regression (MCR-NLR). The MCR-NLR method turns out to be more robust
      and leads to better resolution of the pure components than classic MCR.

PMID- 15261622
TI  - Spin-lattice relaxation and a fast T1-map acquisition method in MRI with
      transient-state magnetization.
AB  - The magnetization under the spin-lattice relaxation and the nuclear magnetic
      resonance radiofrequency (RF) pulses is calculated for a signal RF pulse train
      and for a sequence of multiple RF pulse-trains. It is assumed that the transverse
      magnetization is zero when each RF pulse is applied. The result expressions can
      be grouped into two terms: a decay term, which is proportional to the initial
      magnetization M0, and a recovery term, which has no M0 dependence but strongly
      depends on the spin-lattice relaxation and the equilibrium magnetization Meq. In
      magnetic resonance pulse sequences using magnetization in transient state, the
      recovery term produces artifacts and can seriously degrade the function of the
      preparation sequence for slice selection, contrast weighting, phase encoding,
      etc. This work shows that the detrimental effect can be removed by signal
      averaging in an eliminative fashion. A novel fast data acquisition method for
      constructing the spin-lattice relaxation (T1) map is introduced. The method has
      two features: (i) By using eliminative averaging, the curve to fit the T1 value
      is a decay exponential function rather than a recovery one as in conventional
      techniques; therefore, the measurement of Meq is not required and the result is
      less susceptible to the accuracy of the inversion RF pulse. (ii) The decay
      exponential curve is sampled by using a sequence of multiple pulse-trains. An
      image is reconstructed from each train and represents a sample point of the
      curve. Hence a single imaging sequence can yield multiple sample points needed
      for fitting the T1 value in contrast to conventional techniques that require
      repeating the imaging sequence for various delay values but obtain only one
      sample point from each repetition.

PMID- 15261623
TI  - Fast 29Si magic-angle-spinning NMR acquisitions by RAPT-CP 27Al --> 29Si
      polarization transfer.
AB  - Using enhancement of the 27Al central-transition magnetization by applying RAPT
      prior to 27Al --> 29Si cross-polarization, we demonstrate fast acquisition of
      29Si one-dimensional MAS and two-dimensional 27Al-29Si HETCOR spectra on a new
      sialon phase Ba2Al3Si9N13O5.

PMID- 15261624
TI  - Carr-Purcell echo spectra in the studies of lineshape effects. Nonclassical
      hindered rotation of methyl groups in 1,2,3,4-tetrachloro-9,10
      dimethyltriptycene.
AB  - In the standard NMR spectra, the lineshape patterns produced by a molecular rate
      process are often poorly structured. When alternative theoretical models of such
      a process are to be compared, even quantitative lineshape fits may then give
      inconclusive results. A detailed description is presented of an approach
      involving fits of the competing models to series of Carr-Purcell echo spectra.
      Its high discriminative power has already been exploited in a number of cases of
      practical significance. An explanation is given why it can be superior to methods
      based on the standard spectra. Its applicability in practice is now illustrated
      on example of the methyl proton spectra in 1,2,3,4-tetrachloro-9,10
      dimethyltriptycene TCDMT. It is shown that, in the echo spectra, the recently
      discovered effect of nonclassical stochastic reorientation of the methyl group
      can be identified clearly while it is practically nondiscernible in the standard
      spectra of TCDMT. This is the first detection of the effect at temperatures above
      200 K. It is also shown that in computer-assisted interpretation of exchange
      broadened echo spectra, the usual description of the stimulating radiofrequency
      pulses in terms of rotation operators ought to be replaced by a more realistic
      pulse model.

PMID- 15261625
TI  - Transverse relaxation in the rotating frame induced by chemical exchange.
AB  - In the presence of radiofrequency irradiation, relaxation of magnetization
      aligned with the effective magnetic field is characterized by the time constant
      T1rho. On the other hand, the time constant T2rho characterizes the relaxation of
      magnetization that is perpendicular to the effective field. Here, it is shown
      that T2rho can be measured directly with Carr-Purcell sequences composed of a
      train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2rho
      characterizes the relaxation of the magnetization, which under adiabatic
      conditions remains approximately perpendicular to the time-dependent effective
      field. Theory is derived to describe the influence of chemical exchange on T2rho
      relaxation in the fast-exchange regime, with time constant defined as T2rho,ex.
      The derived theory predicts the rate constant R2rho,ex (= 1/T2rho,ex) to be
      dependent on the choice of amplitude- and frequency-modulation functions used in
      the AFP pulses. Measurements of R2rho,ex of the water/ethanol exchanging system
      confirm the predicted dependence on modulation functions. The described
      theoretical framework and adiabatic methods represent new tools to probe
      exchanging systems.

PMID- 15261626
TI  - Transverse relaxation mechanisms in articular cartilage.
AB  - Relaxation rates in the rotating frame (R1rho) and spin-spin relaxation rates
      (R2) were measured in articular cartilage at various orientations of cartilage
      layer to the static magnetic field (B0), at various spin locking field strengths
      and at two different static magnetic field strengths. It was found that R1rho in
      the deep radial zone depended on the orientation of specimens in the magnet and
      decreased with increasing the spin locking field strength. In contrast, R1rho
      values in the transitional zone were nearly independent of the specimen
      orientation and the spin locking field strength. Measurements of the same
      specimens at 2.95 and 7.05 T showed an increase of R1rho and most R2 values with
      increasing B0. The inverse B0 dependence of some R2 values was probably due to a
      multicomponent character of the transverse magnetization decay. The experiments
      revealed that the dominant T1rho and T2 relaxation mechanism at B0 < or = 3 T is
      a dipolar interaction due to slow anisotropic motion of water molecules in the
      collagen matrix. On average, the contribution of scalar relaxation due to rapid
      proton exchange in femoral head cartilage at 2.95 T is about 6% or less of the
      total R1rho at the spin locking field of 1000 Hz.

PMID- 15261627
TI  - Surface normal imaging with a hand-held NMR device.
AB  - Recently the capabilities of single sided nuclear magnetic resonance (NMR)
      devices have been extended towards three-dimensional imaging. This paper details
      the use of a magnetic field sweep coil to obtain spatial resolution in the plane
      normal to the surface of a hand-held NMR device-the NMR-Mobile Universal Surface
      Explorer (MOUSE). One-dimensional depth profiles can be recorded by varying the
      current in the sweep coils. Preliminary results from multi-layer rubber and glass
      sample phantoms demonstrate a sample penetration depth of 7 mm. Two-dimensional
      images were acquired via the inclusion of phase encoding coils. Non-destructive
      cross-sectional images of small rubber phantoms were successfully recorded.

PMID- 15261628
TI  - Restricted diffusion within a single pore.
AB  - The time-dependent diffusion of 3Heatoms perpendicular to the axis of a single
      macroscopically large cylindrical pore is studied using a steady (or constant)
      gradient-recalled echo sequence. Measurements of the effective 3Hediffusion
      coefficient extending from the free-diffusion regime to the motionally averaged
      regime are presented, and are well-described by analytic solutions to the Bloch
      Torrey equation based on the gaussian phase approximation. Our data yield the
      value 0.140(6)m2/s for the self diffusion coefficient of 3Heat a temperature of
      296 K and a pressure of 1.00 Torr. Adaptations of these methods should enable the
      study of complex pore geometries as model systems.

PMID- 15261629
TI  - A distributed equivalent magnetic current based FDTD method for the calculation
      of E-fields induced by gradient coils.
AB  - This paper evaluates a new, low-frequency finite-difference time-domain method
      applied to the problem of induced E-fields/eddy currents in the human body
      resulting from the pulsed magnetic field gradients in MRI. In this algorithm, a
      distributed equivalent magnetic current is proposed as the electromagnetic source
      and is obtained by quasistatic calculation of the empty coil's vector potential
      or measurements therein. This technique circumvents the discretization of
      complicated gradient coil geometries into a mesh of Yee cells, and thereby
      enables any type of gradient coil modelling or other complex low frequency
      sources. The proposed method has been verified against an example with an
      analytical solution. Results are presented showing the spatial distribution of
      gradient-induced electric fields in a multi-layered spherical phantom model and a
      complete body model.

PMID- 15261630
TI  - Nuclear magnetic resonance-compatible furnace for high temperature MR imaging and
      spectroscopy in situ.
AB  - A high temperature magnetic resonance compatible furnace for real time in situ
      monitoring of materials, processes, and chemical reactions with magnetic
      resonance imaging and spectroscopy is described. Design issues are analyzed.
      Example applications are demonstrated with a time sequence of proton images of
      the binder burnout in a porous green ceramic cylinder containing polyethylene
      glycol binder at 200 degrees C, and 7Li images of the molten salt LiCl at 700
      degrees C.

PMID- 15261631
TI  - Analysis of EPR-time profiles of transient radicals with unresolved spectra.
AB  - A method for analysing EPR-time profiles of transient radicals in solution with
      unresolved hyperfine structure is proposed. It is based on considering the
      magnetic field integral of the magnetization, i.e., the total EPR signal
      intensity, instead of single components of overlapping EPR transitions. For a
      radical system involving chemical kinetics, chemically induced electron
      polarization (CIDEP), and spin relaxation, an analytical solution is found for
      the evolution of the integral magnetization in the Laplace domain. The solution
      in the time domain is given for the case of negligible saturation, i.e.,
      omega2(1)T1T2 << 1. The formulae presented are suitable to avoid equivocal multi
      parameter fits when analysing the results of time-resolved continuous-wave EPR
      experiments for the observables, which characterize the chemical kinetics, CIDEP,
      and electron spin relaxation of radical systems.

PMID- 15261632
TI  - High resolution heteronuclear correlation NMR spectroscopy between quadrupolar
      nuclei and protons in the solid state.
AB  - A high resolution two-dimensional solid state NMR experiment is presented that
      correlates half-integer quadrupolar spins with protons. In this experiment the
      quadrupolar nuclei evolve during t1 under a split-t1, FAM-enhanced MQMAS pulse
      scheme. After each t1 period ending at the MQMAS echo position, single quantum
      magnetization is transferred, via a cross polarization process in the mixing
      time, from the quadrupolar nuclei to the protons. High-resolution proton signals
      are then detected in the t2 time domain during wPMLG5* homonuclear decoupling.
      The experiment has been demonstrated on a powder sample of sodium citrate and
      23Na-1H 2D correlation spectra have been obtained. From the HETCOR spectra and
      the regular MQMAS spectrum, the three crystallographically inequivalent Na+ sites
      in the asymmetric unit were assigned. This MQMAS-wPMLG HETCOR pulse sequence can
      be used for spectral editing of half-integer quadrupolar nuclei coupled to
      protons.

PMID- 15261633
TI  - The presence of long-lived spin states in organic solids with rapid molecular
      motions.
AB  - For organic solids with sufficiently mobile molecular segments, the application
      of a long and weak pulse (gammaB1/2pi approximately Hz) can yield inverted sharp
      peaks with linewidths of approximately 100 Hz in the 1H NMR spectra, and the use
      of multi-frequency weak pulses can excite multiple inverted sharp peaks. For
      these compounds, the normal 1H free induction decay (FID) of a static sample
      contains a slowly decaying part, which can be detected by acquisition delay up to
      about 2 ms. The presence of highly mobile molecular segments can also be
      identified by using a "dipolar filter."

PMID- 15261634
TI  - What teenagers are doing right: changes in sexual behavior over the past decade.

PMID- 15261635
TI  - Fast tracking for critical issues in adolescent health and medicine.

PMID- 15261636
TI  - Can changes in sexual behaviors among high school students explain the decline in
      teen pregnancy rates in the 1990s?
AB  - PURPOSE: To explore the utility of using national data from high school students
      to explain changes in national declines in pregnancy rates. Although declines in
      teen pregnancy and birthrates in the 1990s have been welcome news to those
      interested in adolescent health and welfare, the reasons for these declines are
      not readily apparent. Previous attempts to explain these declines focused on the
      period before 1995 and did not directly calculate the impact of improved
      contraceptive use. METHODS: The national Youth Risk Behavior Survey provided
      estimates for sexual activity and contraceptive use among teens aged 15-17 years
      between 1991 and 2001 (n = 31,058). These data were combined with method-specific
      contraceptive failure rates (CFRs) derived from the 1988 and 1995 National Survey
      of Family Growth and pregnancy rates from the National Vital Statistics System.
      We calculated weighted-average CFRs (WACFR) and used the annual rate of change in
      the WACFR and sexual activity to estimate their relative contributions to the
      annual change in risk of pregnancy. Weighted least-squares regression in SUDAAN
      was used to test change over time. RESULTS: Between 1991 and 2001, annual rates
      of change in sexual behaviors were -1.7% for sexual experience and -1.6% for the
      WACFR. Improvements in WACFR resulted primarily from a decline in use of
      withdrawal (from 20% to 13%) and use of no method (from 17% to 13%) and an
      increase in condom use (40% to 51%). Recent sexual intercourse (i.e., intercourse
      during the past 3 months among teens who had ever had intercourse) did not change
      over time. The change in the estimated risk of pregnancy closely approximated the
      annual decline in the pregnancy rates for blacks and Hispanics but underestimated
      the actual decline for whites. Overall, 53% of the decline in pregnancy rates can
      be attributed to decreased sexual experience (95%CI 26% to 79%) and 47% to
      improved contraceptive use (95%CI 21% to 74%). CONCLUSIONS: Use of school-based
      behavior data reflects well the pregnancy experience for school-age black and
      Hispanic adolescents, but does not track well with the pregnancy risk of white
      adolescents. Care should be taken in attributing changes in pregnancy rates to
      changes in behavior, given broad confidence intervals around these estimates.
      These data suggest that both delayed initiation of sexual intercourse and
      improved contraceptive practice contributed equally to declines in pregnancy
      rates among high school-aged teens during the 1990s; however, estimates varied
      among racial and ethnic groups.

PMID- 15261637
TI  - Assessing health risk behaviors among adolescents: the effect of question wording
      and appeals for honesty.
AB  - PURPOSE: To understand how methodological factors influence prevalence estimates
      of health-risk behaviors obtained from surveys, we examined the effect of varying
      question wording and honesty appeals while holding other aspects of the surveys
      constant. METHODS: A convenience sample of students (n = 4140) in grades 9
      through 12 was randomly assigned to complete one of six versions of a paper-and
      pencil questionnaire in classrooms. Each questionnaire version represented a
      different combination of honesty appeal (standard vs. strong) and questionnaire
      type. The questionnaire types varied in wording and in the number of questions
      assessing particular types of behaviors. The questionnaires were based on those
      used in three national surveys--the Youth Risk Behavior Survey, Monitoring the
      Future, and the National Household Survey on Drug Abuse. Logistic regression
      analyses examined how responses to each survey question assessing behavior were
      associated with questionnaire type, honesty appeal, and the interaction of those
      two variables. RESULTS: Among 32 behaviors with different question wording across
      questionnaire types, 12 showed a significant effect of questionnaire type. Among
      45 behaviors with identical question wording across questionnaire types, five
      showed a significant main effect of questionnaire type. Among all 77 behaviors,
      one showed a significant main effect for honesty appeal and two showed a
      significant interaction between honesty appeal and questionnaire type.
      CONCLUSIONS: When population, setting, questionnaire context, mode of
      administration, and data-editing protocols are held constant, differences in
      question wording can create statistically significant differences in some
      prevalence estimates. Varying honesty appeals does not have an effect on
      prevalence estimates.

PMID- 15261638
TI  - Provider self-efficacy and the screening of adolescents for risky health
      behaviors.
AB  - PURPOSE: To examine the extent to which providers' perceived self-efficacy to
      deliver adolescent preventive services relates to their screening practices.
      METHODS: Screening rates were determined by both provider self-reported screening
      practices and the independent report of the adolescent patient. First, 66
      pediatric providers (pediatricians and nurse-practitioners), working in three
      pediatric clinics within a managed care organization, completed surveys
      assessing: (a) self-efficacy for screening adolescent patients in the areas of
      tobacco use, alcohol use, sexual behavior, seat belt use, and helmet use; and (b)
      self-reported screening of adolescents during well-visits over the past month.
      Second, a sample of patients, aged 14 years to 16 years, reported on whether
      their clinicians screened them for these behaviors during a well-visit.
      Adolescents completed reports (N = 323) immediately following the well visit.
      Data were analyzed using Pearson product-moment correlation coefficients.
      RESULTS: Provider self-efficacy to deliver preventive services was correlated
      with self-reported screening in each of the five content areas, ranging from r =
      .24 (p < .05) for seat belt use to r = .51 (p < .001) for helmet use. Provider
      self-efficacy was significantly related to adolescent reports of screening in
      three of the five content areas; r = .25 (p < .05) for sexual behavior and
      tobacco use; and r = .23 (p = .06) for alcohol use. CONCLUSIONS: Providers' self
      efficacy to screen adolescents for risky behaviors was significantly related to
      both clinician self-report and independent adolescent reports of screening during
      well-visits. These findings point to the importance of enhancing clinicians'
      sense of competence to deliver adolescent preventive services.

PMID- 15261639
TI  - Attitudinal and contextual factors associated with discussion of sexual issues
      during adolescent health visits.
AB  - PURPOSE: To examine attitudinal and contextual factors associated with the
      occurrence of sexual health assessments during adolescent primary care visits.
      METHODS: A total of 313 primarily African-American youth aged 11-21 years from 16
      community-based organizations in suburban Maryland and in New York City completed
      questionnaires focusing on sexually transmitted diseases (STD) and health care.
      The analysis examined the relationship of sexual activity, attitudes, and
      presence of the parent at the health care visit with discussion of three sexual
      health topics and testing for STD at the most recent health care visit. Data were
      analyzed using Chi-square tests and logistic regression. RESULTS: Overall, 74% of
      respondents reported that they had talked about at least one sexual health topic
      at their last health care visit but only 32% had discussed all three topics of
      sexual behavior, birth control, and STD. Females were more likely than males to
      discuss birth control although there were no gender differences in the overall
      likelihood of talking about a sexual health topic. Few adolescents initiated
      discussion of sexual issues. Positive attitudes toward discussing sexual issues
      with a provider and absence of a parent at the visit were independently
      associated with higher odds of discussing at least one sexuality topic and STD
      testing. CONCLUSIONS: Although relatively large numbers of adolescents in the
      sample received sexual health assessments, the proportion was below recommended
      guidelines. The opportunity to speak privately with a clinician and having
      positive attitudes about discussing sex with a doctor appear to be important
      influences on the receipt of sexual health assessments. Improving the quality of
      adolescent preventive care will require creating a health care environment that
      facilitates discussion of sexual health issues.

PMID- 15261640
TI  - Heightened vulnerability and increased risk-taking among adolescent chat room
      users: results from a statewide school survey.
AB  - PURPOSE: To profile adolescent Internet chat room users in terms of demographic
      characteristics, psychological and environmental factors, and behavioral risk
      factors. METHODS: The study sample was drawn from respondents to an anonymous
      statewide survey of 50,168 9th-grade public school students and included 40,376
      students who reported Internet access at home and 19,511 who accessed chat rooms.
      Data were collected by the Minnesota Student Survey (MSS), a survey that has been
      administered triennially by the state's education department to public school
      students in grades 6, 9, and 12 since 1989. The MSS includes more than 117
      questions (300 variables) addressing attitudinal, behavioral, and environmental
      issues. Data analysis consisted of comparing the odds of a particular
      characteristic or behavior for chat room users with that of nonusers. Analyses
      were run separately for boys and girls. The homogeneity of odd ratios was tested
      with the Breslow-Day statistic using SPSS for Windows. RESULTS: For boys and
      girls, use of Internet chat rooms was associated with psychological distress, a
      difficult living environment, and a higher likelihood of risky behaviors.
      Although most chat room users did not report serious problems, this group
      included a disproportionate number of troubled individuals. CONCLUSIONS: Because
      chat room use serves as an indicator of heightened vulnerability and risk-taking,
      parents and others need to be aware of potential dangers posed by online contact
      between strangers and youth.

PMID- 15261641
TI  - Prevalence of partner violence in same-sex romantic and sexual relationships in a
      national sample of adolescents.
AB  - PURPOSE: To present the first national prevalence estimates of psychological and
      physical intimate partner violence between adolescents in same-sex relationships.
      METHODS: Analyses focus on 117 adolescents aged 12-21 years (50% female) from
      Wave II of the National Longitudinal Study of Adolescent Health who reported
      exclusively same-sex romantic or sexual relationships in the 18 months before
      interview. Items from the Conflict Tactics Scale were used to measure partner
      violence victimization. Data analysis included computation of prevalence
      estimates and a logistic regression analysis to assess associations between
      sociodemographic characteristics and violence victimization. RESULTS: Almost one
      quarter of adolescents with same-sex romantic or sexual partners reported some
      type of partner violence victimization; about 1 in 10 reported physical
      victimization. Significant sex differences were found (OR = .29, CI = 0.08,
      1.00), with males being less likely than females to report "any violence." Of six
      other sociodemographic characteristics examined, importance of religion (OR =
      .27, CI = 0.07-1.07) and school size (OR = .32, CI = 0.09-1.11) were associated
      with victimization at the p < .10 level. Adolescents who reported that religion
      was important to them and adolescents who attended larger schools were at lower
      risk of "any violence." CONCLUSIONS: As with opposite-sex relationships,
      psychological and minor physical violence victimization is common among
      adolescents involved in same-sex intimate relationships. Males reporting
      exclusively same-sex relationships were less likely than females to report
      experiencing the violence behaviors examined.

PMID- 15261642
TI  - Mental disorder and comorbidity among runaway and homeless adolescents.
AB  - PURPOSE: To investigate prevalence of mental disorder and comorbidity among
      homeless and runaway adolescents in small to medium sized cities in four
      Midwestern states. METHODS: The study presents lifetime, 12-month prevalence, and
      comorbidity rates for five mental disorders (conduct disorder, major depressive
      episode, posttraumatic stress disorder, alcohol abuse, and drug abuse) based on
      UM-CIDI and DISC-R structured interviews from the baseline interviews of a
      longitudinal diagnostic study of 428 (187 males; 241 females) homeless and
      runaway adolescents aged 16-19 years (mean age = 17.4 years, SD = 1.05). The data
      were collected by full-time street interviewers on the streets and in shelters in
      eight Midwestern cities of various populations. Separate logistic regression
      models were used to investigate factors associated with meeting criteria for any
      disorder and two or more disorders. RESULTS: Lifetime prevalence rates were
      compared with rates for same-aged respondents from the National Comorbidity
      Survey (NCS). Homeless and runaway adolescents were six times more likely than
      same-aged NCS respondents to meet criteria for two or more disorders and were
      from two to 17 times more likely to meet criteria for individual disorders than.
      CONCLUSIONS: Homeless and runaway adolescents in small and mid-sized Midwestern
      cities report significant levels of mental disorder and comorbidity that are
      comparable and often exceed that reported in studies of larger magnet cities.

PMID- 15261643
TI  - HIV risk behavior among ethnically diverse adolescents living in low-income
      housing developments.
AB  - PURPOSE: To describe patterns and predictors of HIV risk behaviors among
      ethnically diverse, low-income adolescents. METHODS: Computer-assisted surveys
      were administered to 1172 adolescents between the ages of 12 and 17 years living
      in 15 low-income housing developments in three urban areas in the United States
      to characterize and identify predictors of HIV risk behavior. Data were analyzed
      using multinomial logistic regression to identify variables predictive of "no
      risk," "lower risk," and "higher risk" group classification. RESULTS: Most
      adolescents were not yet sexually active; nonetheless, a subset of youth reported
      high rates of HIV risk-related behaviors. HIV risk was highest among adolescents
      who were older, had weaker intentions to reduce risk, stronger beliefs that their
      sexual partners did not favor risk-reduction, lower risk-reduction behavioral
      skills, higher risk-reduction outcome expectation, and higher rates of substance
      use. CONCLUSIONS: HIV prevention efforts are needed that are tailored to
      ethnically diverse communities of adolescents, including those in early
      adolescence and those at highest risk.

PMID- 15261644
TI  - Familial juvenile hypertrophy of the breast.
AB  - OBJECTIVE: Juvenile (virginal) hypertrophy of the breast (JHB) is a relatively
      rare condition leading to gigantomastia in peripubertal females. The pathology is
      limited usually to the breast, with otherwise normal growth and development and
      without any other deformities. The rapid growth of the breast (bilateral or
      unilateral) in adolescent girls leads to significant physical and psychological
      difficulties. This gigantomastia is treated surgically by breast reduction or
      mastectomy and its modification. Familial JHB was described only once in the
      literature, and its etiology is unknown. RESULTS: We report here on a familial
      pattern of juvenile hypertrophy of the breast accompanied by congenital
      anonychia. To the best of our knowledge, this is the first report of such a
      presentation. Our study dealt with four members of the same family, related
      through their fathers, enduring congenital anonychia of hands and feet with no
      functional limitation and who showed rapid uncontrolled breast enlargement in
      prepubertal age. This was severe enough to cause the curtailment of their social
      activity and cessation of schooling. The mothers of all four patients had normal
      breasts and nails, whereas their fathers had anonychia. The genetic basis for the
      association between the two clinical findings is yet to be determined.
      CONCLUSION: The four girls underwent breast reduction surgery.

PMID- 15261645
TI  - Allergic symptoms and microflora in schoolchildren.
AB  - We studied 867 junior high school children and administered a questionnaire
      documenting allergic symptoms and environmental variables, and measured
      Immunoglobulin E serum levels and the immunoglobulin G titers of serum antibody
      to microflora. A total of 716 subjects were ultimately used for statistics; those
      with at least two of the following allergic symptoms: asthma, rhinitis, eczema,
      or food allergy, showed significantly higher IgG titers to Bactroides vulgatus
      than other groups. This finding suggests that a species of the Bacteroides genus
      of the intestinal microflora tends to affect the gut issues, but further studies
      are needed to clarify this.

PMID- 15261646
TI  - Pattern formation and developmental mechanisms: super-models of development.

PMID- 15261647
TI  - Large-scale analysis of pseudogenes in the human genome.
AB  - Pseudogenes are considered as genomic fossils: disabled copies of functional
      genes that were once active in the ancient genome. Recently, whole-genome
      computational approaches have revealed thousands of pseudogenes in the genomes of
      the human and other eukaryotes. Identification of these pseudogenes can improve
      the accuracy of gene annotation. It also offers new insight on the evolutionary
      history and the stability of the genome as a whole.

PMID- 15261648
TI  - Development through the eyes of functional genomics.
AB  - In many of the model organisms used to study development, it is becoming
      relatively routine to carry out global analyses of gene function. These analyses
      take many forms, from microarray analyses to the construction of physical
      interaction maps to the systematic analyses of loss-of-function phenotypes. Such
      large-scale datasets can be integrated to generate complex gene networks, and we
      explore how these gene networks can contribute to an understanding of
      developmental pathways. In particular, we examine how combining large-scale
      expression experiments and gene networks may move us towards a molecular
      description of the events of development, embodied in a succession of stage
      specific subnetworks sampled from an organism's overall gene network.

PMID- 15261649
TI  - Integrating transcriptional and signalling networks during muscle development.
AB  - A fundamental aspect of developmental decisions is the ability of groups of cells
      to obtain the competence to respond to different signalling inputs. This
      information is often integrated with intrinsic transcriptional networks to
      produce diverse developmental outcomes. Studies in Drosophila are starting to
      reveal a detailed picture of the regulatory circuits controlling the subdivision
      of the dorsal mesoderm, which gives rise to diverse muscle types including
      cardioblasts, pericardial cells, body wall muscle and gut muscle. The combination
      of a common set of mesoderm autonomous transcription factors (e.g. Tinman and
      Twist) and spatially restricted inductive signals (e.g. Dpp and Wg) subdivide the
      dorsal mesoderm into different competence domains. The integration of additional
      signalling inputs with localised repression within these competence domains
      results in diverse transcriptional responses within neighbouring cells, which in
      turn generates muscle diversity.

PMID- 15261650
TI  - Gene regulatory network controlling embryonic specification in the sea urchin.
AB  - The current state of the gene regulatory network for endomesoderm specification
      in sea urchin embryos is reviewed. The network was experimentally defined, and is
      presented as a predictive map of cis-regulatory inputs and functional regulatory
      gene interconnections (updated versions of the network and most of the underlying
      data are at ). The network illuminates the 'whys' of many aspects of zygotic
      control in early sea urchin development, both spatial and temporal. The network
      includes almost 50 genes, and these are organized in subcircuits, each of which
      executes a particular regulatory function.

PMID- 15261651
TI  - The interface between cell and developmental biology.
AB  - Cell differentiation, morphology, migration, polarity, intercellular
      communication and adhesion are all cellular processes that control embryo
      morphogenesis and lie at the interface of cell and developmental biology. The
      interface between these two fields is best illustrated, however, in studies of
      axiation and cytoskeletal remodeling during development. Recent advances reveal
      novel mechanisms for axiation, including the role of RNA and protein degradation
      in regulating the timely expression of morphogenetic signals. Significant
      progress has also been made in identifying components of the cytoskeleton and the
      extracellular matrix that mediate embryonic cell migration and polarity. Cellular
      processes at the interface of cell and developmental biology are overseen by the
      Wnt signaling cascade that coordinates both axiation and cytoskeletal remodeling
      during development.

PMID- 15261652
TI  - Interplay of mechanical deformation and patterned gene expression in developing
      embryos.
AB  - The shaping of the early embryo requires pattern formation as well as geometric
      and topological morphogenesis of the developing tissues. The morphogenetic
      movements that lead to geometric shape changes are controlled by patterned gene
      expression. How particular movements are related to patterning genes, and which
      underlying molecular and cellular mechanisms lead to coordinated macroscopic
      movements that induce morphogenesis, remain the challenging questions of
      embryonic development. How morphogenetic movements could modulate the expression
      of developmental genes is an emerging question, potentially opening new horizons
      in developmental biology. This question instigates the task of characterizing the
      molecular and cellular mechanisms underlying these mechano-transcription events.

PMID- 15261653
TI  - Models of cell signaling pathways.
AB  - Cellular signaling circuits handle an enormous range of computations. Beyond the
      housekeeping, replicating and other functions of individual cells, signaling
      circuits must implement the immensely complex logic of development and function
      of multicellular organisms. Computer models are useful tools to understand this
      complexity. Recent studies have extended such models to include electrical,
      mechanical and spatial details of signaling, and to address the stochastic
      effects that arise when small numbers of molecules interact. Increasing numbers
      of models have been developed in close conjunction with experiments, and this
      interplay gives a deeper and more reliable insight into signaling function.

PMID- 15261654
TI  - Digital three-dimensional models of Drosophila development.
AB  - Digital models of organs, cells and subcellular structures have become important
      tools in biological and medical research. Reaching far beyond their traditional
      widespread use as didactic tools, computer-generated models serve as electronic
      atlases to identify specific elements in complex patterns, and as analytical
      tools that reveal relationships between such pattern elements that would remain
      obscure in two-dimensional sections. Digital models also offer the unique
      opportunity to store and display gene-expression patterns, and pilot studies have
      been made in several genetic model organisms, including mouse, Drosophila and
      Caenorhabditis elegans, to construct digital graphic databases intended as
      repositories for gene-expression data.

PMID- 15261655
TI  - Dictyostelium morphogenesis.
AB  - During starvation-induced Dictyostelium development, up to several hundred
      thousand amoeboid cells aggregate, differentiate and form a fruiting body. The
      chemotactic movement of the cells is guided by the rising phase of the outward
      propagating cAMP waves and results in directed periodic movement towards the
      aggregation centre. In the mound and slug stages of development, cAMP waves
      continue to play a major role in the coordination of cell movement, cell-type
      specific gene expression and morphogenesis; however, in these stages where cells
      are tightly packed, cell-cell adhesion/contact-dependent signalling mechanisms
      also play important roles in these processes.

PMID- 15261656
TI  - Models of morphogenesis: the mechanisms and mechanics of cell rearrangement.
AB  - The directional rearrangement of cells is a key mechanism for reshaping embryos.
      Despite substantial recent progress in understanding the basic signal
      transduction pathways that allow cells to orient themselves in space, the
      extrinsic cues that activate these pathways are just beginning to be understood.
      Even less-well understood are the physical mechanisms cells use to change
      position, especially when those cells are epithelial, and how mechanical forces
      within the embryo affect those movements. Recent studies are providing clues
      regarding how this fundamental process occurs with such remarkable reliability.

PMID- 15261657
TI  - The vertebrate segmentation clock.
AB  - In vertebrate embryos, somite segmentation is controlled by a molecular clock, in
      the form of a transcriptional oscillator that operates in the presomitic
      mesoderm. Most of the genes implicated in the oscillator belong to the Notch
      pathway; a recently discovered exception is the Wnt pathway gene Axin2.
      Experiments have revealed several negative feedback loops that might generate
      oscillations, leading to at least four different theories. The simplest of these
      is based on direct autoinhibition of certain members of the hairy/E(spl) family
      of Notch target genes--Hes7 in the mouse, and her1 and her7 in the zebrafish. A
      mathematical account of this mechanism explains some surprising observations and
      suggests that the period of oscillation is chiefly determined by the
      transcriptional and translational delays--the times required to make a molecule
      of the mRNA and a molecule of the protein.

PMID- 15261658
TI  - Exploring alternative models of rostral-caudal patterning in the zebrafish
      neurectoderm with computer simulations.
AB  - The StarLogo and NetLogo programming environments allow developmental biologists
      to build computer models of cell-cell interactions in an epithelium and visualize
      emergent properties of hypothetical genetic regulatory networks operating in the
      cells. These environments were used to explore alternative models that show how a
      posteriorizing morphogen gradient might define gene-expression domains along the
      rostral-caudal axis in the zebrafish neurectoderm. The models illustrate how a
      hypothetical genetic network based on auto-activation and cross-repression could
      lead to establishment of discrete non-overlapping gene-expression domains.

PMID- 15261659
TI  - Creating a two-dimensional pattern de novo during Arabidopsis trichome and root
      hair initiation.
AB  - During plant epidermal differentiation, root hairs and leaf hairs (trichomes)
      become specified in a regular pattern. Although the underlying mechanisms appear
      to be different in that the position of root hairs is determined by their
      position with respect to the underlying cortical cells and that of the trichomes
      appears to be generated de novo, a common set of genes was found to operate in
      both systems. A complex of transcription factors appears to be involved in
      creating the pattern and cell-cell movement of small transcription factors is
      postulated to mediate cell-cell communication.

PMID- 15261660
TI  - Bio-switches: what makes them robust?
AB  - Ideas of how a system of interacting enzymes can act as a switch are based on the
      concept of bistability of a biochemical network. This means that, because of the
      very structure of a signaling pathway, the system can be in one of two stable
      steady states: active or inactive. Switching from one state to another may then
      occur in response to external stimuli or as a result of internal development.
      However, the bistability of a biochemical network might not be robust enough to
      be the sole mechanism behind bio-switching. On the basis of recent experimental
      data on the cell-cycle G2/M transition during starfish oocyte meiotic maturation,
      it is shown that cooperative phenomena--such as phase changes associated with
      clustering, dissolution of aggregates and so on--may play central roles in
      providing a decisive and irreversible transition.

PMID- 15261661
TI  - Elucidating mechanisms underlying robustness of morphogen gradients.
AB  - Morphogen gradients play a pivotal role in most phases of developmental
      patterning. To ensure proper patterning, reproducible gradients are established
      under diverse environmental conditions and genetic backgrounds. We refer to the
      capacity to buffer fluctuations in gene dosage or environmental conditions as
      'robustness'. By theoretical analysis of mechanisms that facilitate robustness,
      it is possible to unravel the machinery responsible for generating the spatial
      distribution of morphogens.

PMID- 15261662
TI  - Noise, delays, robustness, canalization and all that.
AB  - A biological system such as a developing embryo can withstand many perturbations.
      What is the basis of this robustness both against noise and mutation? Recent
      advances in modeling may throw new light on this old problem. First, recent
      theoretical and experimental work clearly demonstrates the importance of noise
      and time delays for the proper functioning of genetic networks: noise and delays
      are simply part of the normal operating constraints. By contrast, sweeping
      statements have been made recently about a so-called 'robustness' of biological
      processes, based on work that neglects noise and delays completely. I submit that
      studying the stability of complex biological systems with such omissions is an
      unnecessary, inadequate and potentially disastrous simplification. I review the
      existing alternatives and propose using them to construct a modeling framework
      that overcomes all serious limitations.

PMID- 15261663
TI  - Models for the generation of the embryonic body axes: ontogenetic and
      evolutionary aspects.
AB  - Coelenterates including hydra are assumed to be close to the last common ancestor
      before bilaterality evolved. Models based on local self-enhancement and long
      range inhibition account for pattern formation and regeneration along this
      ancestral axis. The body of a hydra-like ancestor evolved into the brain and
      heart of higher organisms, accounting for the close relationship of both
      patterning processes. Bilateria require a long-extended organizing region to
      pattern their dorsoventral axis. Models reveal the difficulties in the generation
      of such a stripe-like organizer and account for different mechanisms realized in
      vertebrates and insects. Common pathways involved in hydra budding and in the
      formation of appendages in higher organisms suggest a possible link.

PMID- 15261665
TI  - Protein folding and quality control in the endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is a highly versatile protein factory that is
      equipped with chaperones and folding enzymes essential for protein folding. ER
      quality control guided by these chaperones is essential for life. Whereas
      correctly folded proteins are exported from the ER, misfolded proteins are
      retained and selectively degraded. At least two main chaperone classes, BiP and
      calnexin/calreticulin, are active in ER quality control. Folding factors usually
      are found in complexes. Recent work emphasises more than ever that chaperones act
      in concert with co-factors and with each other.

PMID- 15261666
TI  - Differential ER exit in yeast and mammalian cells.
AB  - The coat complex COPII forms vesicles at the endoplasmic reticulum to transport a
      variety of cargo proteins to the Golgi structure. Recent biochemical and
      structural studies reveal the molecular mechanism of cargo protein recognition by
      COPII components. Furthermore, there are at least two distinct ER-to-Golgi
      transport carrier structures carrying different cargo proteins in yeast and
      mammalian cells, suggesting several distinct mechanisms for the concentration,
      selection and exit of cargo proteins from the ER. It will be essential to follow
      the dynamics of transitional ER sites and cargo protein concentration within the
      ER in order to understand how these transport processes occur in living cells.

PMID- 15261667
TI  - The roles of enzyme localisation and complex formation in glycan assembly within
      the Golgi apparatus.
AB  - Cell surface glycans govern numerous cell-cell interactions are therefore key
      determinants of multicellular biology. They originate from biosynthetic pathways
      comprising an assembly line of glycosyltransferases within the Golgi compartment.
      Although the mechanisms of Golgi enzyme localisation are still under debate, the
      distribution of these enzymes among the Golgi cisternae can dictate the overall
      structures produced by the cell. Fine-tuning of glycan biosynthetic pathways is
      further accomplished by specific associations among glycosyltransferases.
      Together, localisation and association govern the assembly of complex glycans and
      thereby regulate interactions at the cell surface.

PMID- 15261668
TI  - Molecular basis for Golgi maintenance and biogenesis.
AB  - The Golgi apparatus contains thousands of different types of integral and
      peripheral membrane proteins, perhaps more than any other intracellular
      organelle. To understand these proteins' roles in Golgi function and in broader
      cellular processes, it is useful to categorize them according to their
      contribution to Golgi creation and maintenance. This is because all of the
      Golgi's functions derive from its ability to maintain steady-state pools of
      particular proteins and lipids, which in turn relies on the Golgi's dynamic
      character - that is, its ongoing state of transformation and outgrowth from the
      endoplasmic reticulum. Here, we categorize the expanding list of Golgi-associated
      proteins on the basis of their role in Golgi reformation after the Golgi has been
      disassembled. Information gained on how different proteins participate in this
      process can provide important insights for understanding the Golgi's global
      functions within cells.

PMID- 15261669
TI  - Membrane lipids and vesicular traffic.
AB  - Lipids were long considered to be passive passengers of carrier vesicles with the
      single role of sealing the transport container. We now know that specific
      phospholipids are required for efficient fusion, while others facilitate budding
      and fission. Moreover, the various polyphosphoinositides assist in the
      recruitment from the cytosol of proteins of the transport machinery. Finally, the
      segregation of membrane lipids into different fluid phases appears to serve as a
      'lipid raft' mechanism for protein sorting at various stages of the secretory and
      endocytic pathways. The current challenge is to understand how proteins control
      the metabolism and subcellular localization, and thereby the activity, of the
      various lipids.

PMID- 15261670
TI  - COP and clathrin-coated vesicle budding: different pathways, common approaches.
AB  - Vesicle and tubule transport containers move proteins and lipids from one
      membrane system to another. Newly forming transport containers frequently have
      electron-dense coats. Coats coordinate the accumulation of cargo and sculpt the
      membrane. Recent advances have shown that components of both COP1 and clathrin
      adaptor coats share the same structure and the same motif-based cargo recognition
      and accessory factor recruitment mechanisms, which leads to insights on conserved
      aspects of coat recruitment, polymerisation and membrane deformation. These
      themes point to the way in which evolutionarily conserved features underpin these
      diverse pathways.

PMID- 15261671
TI  - Cargo recognition during clathrin-mediated endocytosis: a team effort.
AB  - Transmembrane proteins destined to endosomes are selectively accumulated in
      clathrin-coated pits at the plasma membrane and rapidly internalized in clathrin
      coated vesicles. The recognition of specific sequence motifs in transmembrane
      cargo by coated-pit proteins confers specificity on the endocytic process.
      Interaction of membrane cargo with the clathrin adaptor protein complex AP-2 is
      the major mechanism of cargo sorting into coated pits in mammalian cells. Recent
      studies have revealed a variety of alternative mechanisms of cargo recruitment
      involving additional adaptor proteins. These alternative mechanisms appear to be
      particularly important during clathrin-mediated endocytosis of signaling
      receptors.

PMID- 15261672
TI  - Not just a sink: endosomes in control of signal transduction.
AB  - Recent studies indicate that endocytic organelles can play a more active role in
      signal propagation and amplification than was recognised before. By deciphering
      the interplay between endocytosis and signalling, we will be able to gain a more
      sophisticated level of understanding of signal transduction mechanisms.

PMID- 15261673
TI  - Membrane traffic during embryonic development: epithelial formation, cell fate
      decisions and differentiation.
AB  - The analysis of membrane trafficking has in the past mainly dealt with single
      cells in culture. Recent studies of membrane trafficking in Drosophila focus on
      how cells are organized in tissues and form epithelia during embryogenesis.
      During these processes, the specific involvement of distinct biosynthetic and
      endocytic routes is starting to be understood. Once organized in epithelia, cells
      communicate with each other to make cell fate decisions through morphogen
      gradients and lateral inhibition. Endocytosis seems to play unexpected roles in
      shaping morphogen gradients and in biasing lateral inhibition events. Once
      committed to a developmental program, cells differentiate. In the case of
      neurons, trafficking through the biosynthetic and endocytic pathways may give the
      necessary speed of response and versatility to axons that navigate through a
      changing environment during pathfinding.

PMID- 15261674
TI  - Exosomes: endosomal-derived vesicles shipping extracellular messages.
AB  - Exosomes are membrane vesicles released into the extracellular environment upon
      exocytic fusion of multivesicular endosomes with the cell surface. They have a
      particular composition reflecting their origin in endosomes as intraluminal
      vesicles. In vitro and in vivo studies support the contribution of exosomes to an
      acellular mode of communication, leading to intercellular transfer of molecules.
      Exosomes may have regulatory functions in the immune system and their application
      in cancer immunotherapy is promising. The mechanisms involved in exosome
      secretion and interaction with target cells are as yet unclear. A better
      understanding of these mechanisms is also essential to determine the link between
      exosomes and retroviruses.

PMID- 15261675
TI  - Signaling and membrane dynamics during phagocytosis: many roads lead to the
      phagos(R)ome.
AB  - Phagocytosis is the mechanism used by specialized cells such as macrophages,
      dendritic cells and neutrophils to internalize, degrade and eventually present
      peptides derived from particulate antigens. This process relies on profound
      rearrangements of the actin cytoskeleton and the plasma membrane to engulf
      particles. Recent work has highlighted the early recruitment of internal
      membranes derived from endocytic compartments and from the endoplasmic reticulum
      to allow plasma membrane extension at the onset of phagocytosis. This ensures
      that the phagosome is rapidly provided with the machinery appropriate for later
      phagocytic functions, including particle degradation and antigen presentation.

PMID- 15261676
TI  - Intracellular and viral membrane fusion: a uniting mechanism.
AB  - Structural and functional analyses have revealed remarkable mechanistic
      similarities between viral and intracellular fusion. Both fusion processes are
      driven by an orchestrated cascade of protein binding and folding reactions. After
      an initial tethering step, activation of the fusion machinery links the opposing
      membranes and protein folding pulls the membranes in close proximity; fusion
      pores form, open and dilate, and the process culminates in the complete merging
      of the lipid bilayers. Viral fusion is mediated by a single fusion protein,
      whereas the intracellular fusion machinery is split into matching halves, the v-
      and t-SNAREs. SNAREs, together with synaptotagmins, emerge as the key machinery
      for regulated exocytosis.

PMID- 15261677
TI  - Epithelial trafficking: new routes to familiar places.
AB  - Research carried out in mammalian epithelial cell systems over the past 25 years
      has delineated pathways and sorting signals involved in polarized delivery of
      plasma membrane proteins. Recently some progress has been made in the
      identification of mechanisms underlying this polarized trafficking and in the
      visualization of trafficking routes in live cells. A promising area of research
      is the study of trafficking functions of novel polarity genes identified in
      Drosophila and Caenorhabditis elegans.

PMID- 15261678
TI  - Microtubule-dependent transport in neurons: steps towards an understanding of
      regulation, function and dysfunction.
AB  - Intracellular transport by microtubule-dependent motors is crucial for neuronal
      survival and function. Recent advances reveal novel strategies for the regulation
      of transport and the attachment of motors to cargoes. Current findings also
      illustrate the importance of directed transport in neuronal biology, including
      microtubule-motor-dependent transduction of neurotrophic signals and axonal
      damage signal complexes. Furthermore, recent data implicating the dysfunction of
      microtubule-dependent transport in the cause and development of several
      neurodegenerative diseases provides evidence for the vital role of transport in
      neuronal and organismal function.

PMID- 15261679
TI  - Controlling the location and activation of Rab GTPases.
AB  - The remarkable degree of specificity with which Rab GTPases recognise distinct
      subsets of intracellular membranes forms the basis of their ability to act as key
      cellular regulators, determining the recruitment of downstream effectors to the
      right membrane at the right time. The molecular mechanisms controlling Rab
      localisation, however, have proved tricky issues to address. It is becoming
      increasingly apparent that multiple factors contribute to the specificity of Rab
      localisation and the close coordination of membrane targeting with Rab
      activation. With important new insights into the mode of action of the general
      Rab regulators REP and RabGDI, as well as the demonstration that novel factors
      such as Yip3/Pra1 act as GDI displacement factors and that signals within Rab
      proteins contribute to targeting specificity, a better understanding of the
      concepts governing Rab recruitment and function is now beginning to emerge. The
      diversity of cellular processes regulated by Rab family members is made possible,
      not only by the wide range of effectors they recruit, but also by the different
      mechanisms regulating their own targeting and activation.

PMID- 15261680
TI  - The building BLOC(k)s of lysosomes and related organelles.
AB  - Hermansky-Pudlak syndrome defines a group of genetic disorders characterized by
      defects in organelles of the endosomal-lysosomal system, most notably melanosomes
      and platelet-dense granules. About a dozen genes have been implicated in the
      pathogenesis of the disease in humans and mice. Most of these genes encode novel
      polypeptides that are not conserved in unicellular eukaryotes. Recent studies
      have revealed that these polypeptides are stable components of at least three
      distinct, ubiquitously expressed protein complexes, named biogenesis of lysosome
      related organelles complex (BLOC)-1, -2 and -3. These findings provide a
      framework for studies on the function of these proteins and the pathogenesis of
      Hermansky-Pudlak syndrome.

PMID- 15261681
TI  - Cardiac structure and function.

PMID- 15261682
TI  - Valvular disease.

PMID- 15261683
TI  - Myocardial ischemia and infarction.

PMID- 15261684
TI  - Angiography and interventional cardiology.

PMID- 15261685
TI  - Cardiac arrhythmias.

PMID- 15261686
TI  - Vascular disease, hypertension, and prevention.

PMID- 15261687
TI  - Pediatric cardiology and adult congenital heart disease.

PMID- 15261688
TI  - Noninvasive imaging.

PMID- 15261689
TI  - Construction and application of a bovine immune-endocrine cDNA microarray.
AB  - A variety of commercial DNA arrays specific for humans and rodents are widely
      available; however, microarrays containing well-characterized genes to study
      pathway-specific gene expression are not as accessible for domestic animals, such
      as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine
      immune-endocrine cDNA array was developed to evaluate genetic pathways involved
      in the immune-endocrine axis of cattle during periods of altered homeostasis
      provoked by physiological or environmental stressors, such as infection,
      vaccination or disease. For this purpose, 167 cDNA sequences corresponding to
      immune, endocrine and inflammatory response genes were collected and categorized.
      Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate
      dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19,
      beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a
      bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a
      partial sequence of the plasmid pACYC177. In addition, RNA extracted from un
      stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S.
      aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood
      leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific
      primers. The endocrine-associated genes were amplified from cDNA derived from un
      stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The
      array was constructed in 4 repeating grids of 180 duplicated spots by coupling
      the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass
      slides. The bovine immune-endocrine arrays were standardized and preliminary gene
      expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated
      and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate
      arrays/cow) in a time course study. Mononuclear cell-derived cytokine and
      chemokine (IL-2, IL-1alpha, TNFalpha, IFN-gamma, TGFbeta-1, MCP-1, MCP-2 and MIP
      3alpha) mRNA exhibited a repeatable and consistently low expression in un
      stimulated cells and at least a two-fold increased expression following 6 and 24
      h ConA stimulation as compared to 0 h un-stimulated controls. In contrast,
      expression of antigen presenting molecules, MHC-DR, MHC-DQ and MHC-DY, were
      consistently at least two-fold lower following 6 and 24 h ConA stimulation. The
      only endocrine gene with differential expression following ConA stimulation was
      prolactin. Additionally, due to the high level of genetic homology between ovine,
      swine and bovine genes, RNA similarly acquired from sheep and pigs was evaluated
      and similar gene expression patterns were noted. These data demonstrate that this
      application-targeted array containing a set of well characterized genes can be
      used to determine the relative gene expression corresponding to immune-endocrine
      responses of cattle and related species, sheep and pigs.

PMID- 15261690
TI  - Cloning and sequencing of badger (Meles meles) interferon gamma and its detection
      in badger lymphocytes.
AB  - The European badger (Meles meles) has been identified as a reservoir for
      Mycobacterium bovis and is implicated in the maintenance and transmission of
      tuberculosis in cattle. There is a need for a sensitive test of M. bovis
      infection in badgers and the current serodiagnostic test used for this purpose
      has low sensitivity. As observed for other species, assay of interferon-gamma
      (IFNgamma) produced in response to M. bovis antigens is a more sensitive test of
      tuberculosis. With this objective in sight, we report the first step in the
      development of an ELISA for badger IFNgamma. The badger IFNgamma gene was cloned
      and sequenced and used to generate a specific polyclonal antibody to the
      cytokine. The gene sequence demonstrated regions that were conserved within the
      IFNgamma genes of other mammals. The badger sequence was most similar to the
      canine, showing similar structural organisation of the gene and 88% amino acid
      identity. Rabbits were immunised with DNA encoding badger IFNgamma and the
      resulting polyclonal antiserum demonstrated specificity for canine IFNgamma by
      immunoblot of a commercial recombinant canine IFNgamma. The antiserum was used to
      detect intracellular badger IFNgamma by flow cytometry analysis of badger
      lymphocytes stimulated with mitogen.

PMID- 15261692
TI  - Induction of auto-anti-idiotypic antibodies specific for antibodies to matrix and
      envelope glycoprotein from pigs experimentally infected with porcine reproductive
      and respiratory syndrome virus.
AB  - Auto-anti-idiotypic antibodies (Aab-2s) specific for antibodies against envelope
      glycoprotein GP5 were previously identified in 10 of 12 pigs experimentally
      infected with porcine reproductive and respiratory syndrome virus (PRRSV). In
      this study, we report in addition the induction of Aab-2s specific for antibodies
      against matrix (M) and envelope glycoprotein GP5 antigens in 38 of 47 pigs
      experimentally infected with PRRSV. Two sets of Aab-2s were induced in the sera,
      one at 21 days post-infection (DPI) and peaked on 35 DPI and another at 49 DPI
      and peaked on 77 DPI. The Aab-2s induced at an early stage were from non-virus
      carrier pigs as defined when they were euthanized on and after 77 DPI. In
      contrast, the Aab-2s induced at a later stage were from virus carrier pigs. These
      Aab-2s possessed the characteristics of internal image Ab-2s and recognized
      shared idiotypes on swine and murine antibodies to the GP5 and M antigens of
      PRRSV. This study further demonstrates that, during the antibody responses to
      PRRSV infection, Aab-2s specific for both anti-M and anti-GP5 antibodies were
      induced. More importantly, the early and late Aab-2s possessed different idiotype
      binding specificities. By detecting and characterizing these Aab-2s, it may be
      possible to identify whether pigs infected with PRRSV will clear the virus or
      become virus carriers.

PMID- 15261691
TI  - Isolation and characterization of pediatric canine bone marrow CD34+ cells.
AB  - Historically, the dog has been a valuable model for bone marrow transplantation
      studies, with many of the advances achieved in the dog being directly
      transferable to human clinical bone marrow transplantation protocols. In
      addition, dogs are also a source of many well-characterized homologues of human
      genetic diseases, making them an ideal large animal model in which to evaluate
      gene therapy protocols. It is generally accepted that progenitor cells for many
      human hematopoietic cell lineages reside in the CD34+ fraction of cells from bone
      marrow, cord blood, or peripheral blood. In addition, CD34+ cells are the current
      targets for human gene therapy of diseases involving the hematopoietic system. In
      this study, we have isolated and characterized highly enriched populations of
      canine CD34+ cells isolated from dogs 1 week to 3 months of age. Bone marrow
      isolated from 2- to 3-week-old dogs contained up to 18% CD34+ cells and this high
      percentage dropped sharply with age. In in vitro 6-day liquid suspension
      cultures, CD34+ cells harvested from 3-week-old dogs expanded almost two times
      more than those from 3-month-old dogs and the cells from younger dogs were also
      more responsive to human Flt-3 ligand (Flt3L). In culture, the percent and number
      of CD34+ cells from both ages of dogs dropped sharply between 2 and 4 days,
      although the number of CD34+ cells at day 6 of culture was higher for cells
      harvested from the younger dogs. CD34+ cells harvested from both ages of dogs had
      similar enrichment and depletion values in CFU-GM methylcellulose assays. Canine
      CD34+/Rho123lo cells expressed c-kit mRNA while the CD34+/Rhohi cells did not.
      When transplanted to a sub-lethally irradiated recipient, CD34+ cells from 1- to
      3-week-old dogs gave rise to both myeloid and lymphoid lineages in the periphery.
      This study demonstrates that canine CD34+ bone marrow cells have similar in vitro
      and in vivo characteristics as human CD34+ cells. In addition, ontogeny-related
      functional differences reported for human CD34+ cells appear to exist in the dog
      as well, suggesting pediatric CD34+ cells may be better targets for gene transfer
      than adult bone marrow. The demonstration of similarities between canine and
      human CD34+ cells enhances the dog as a large, preclinical model to evaluate
      strategies for improving bone marrow transplantation protocols, for gene therapy
      protocols that target CD34+ cells, and to study the engraftment potential of
      various cell populations that may contain hematopoietic progenitor cell activity.

PMID- 15261693
TI  - Increase in gammadelta T cells in the blood of cattle persistently infected with
      bovine leukemia virus following administration of recombinant bovine IFN-gamma.
AB  - To examine the effect of recombinant bovine interferon-gamma (rbIFN-gamma) on
      cattle persistently infected with bovine leukemia virus (BLV), BLV-infected
      cattle were inoculated intraperitoneally with IFN-gamma. All cattle were febrile
      after inoculation with IFN-gamma and then recovered within 48 h. Flow cytometric
      analysis showed that the numbers of CD4+ and CD8+ T cells were decreased for 2-3
      days and then their numbers were recovered. The number of gammadelta T cells
      increased after the fever. In contrast, the number of IgM+ lymphocytes remained
      low for about 1 week. Moreover, the numbers of syncytia produced by peripheral
      blood lymphocytes decreased and remained low compared to that before IFN-gamma
      administration. These results suggest that IFN-gamma induces the up-regulation of
      gammadelta T cells, decreases the number of IgM+ lymphocytes and suppresses the
      growth of BLV in BLV-infected cattle in vivo.

PMID- 15261694
TI  - Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing
      hormone (GnRH-I)--a histological comparison in male animals.
AB  - A N-terminal modified gonadotrophin releasing hormone (GnRH-I, tetanus toxoid
      CHWSYGLRPG-NH2) conjugate was evaluated histologically in a number of male animal
      species (mice, dogs and sheep). The immunogen has previously been shown to be
      highly effective in rats, by suppressing both steroidogenesis and
      spermatogenesis. However, cross-species efficacy of peptide vaccines is known to
      be highly variable. Therefore, a comparative evaluation of reproductive tissues
      from animals immunized against this immunogen adsorbed onto an alum-based
      adjuvant was made. The sheep and dogs were chosen, as use of anti-fertility
      vaccines in these species is important in farming and veterinary practice.
      Changes in testicular size were measured during the immunization period and the
      greatest alteration (attributed to gonadal atrophy) was observed in the rat.
      Following euthanasia, the testicular tissue was evaluated for spermatogenesis.
      The most susceptible species to GnRH-I ablation was the rat, which showed
      significant (P < 0.0001) arrest in spermatogenesis compared with untreated
      controls. Testicular sections taken from treated animals were completely devoid
      of spermatozoa or spermatids, in comparison with 94% of the untreated controls
      showing evidence of spermatogenesis. The immunized mice and rams also showed
      significant arrest (P < 0.0001). There was a 30-45% decrease in spermatogenesis
      and total azoospermia was not apparent. However, the least responsive were the
      dogs, which showed little significant variation compared to untreated animals and
      only a 5% decrease in activity. A comparison of the specific IgG response to GnRH
      I indicated that in sheep and dogs the response was not maintained, unlike in
      rodents, suggesting that suppression of fertility may be due to differences in
      immune responses in different animal species.

PMID- 15261695
TI  - Characteristics of oligodeoxyribonucleotides that induce interferon (IFN)-alpha
      in the pig and the phenotype of the IFN-alpha producing cells.
AB  - The immunostimulatory effects of oligodeoxyribonucleotides (ODN) containing
      unmethylated CpG dinucleotides (CpG-ODN) in certain base contexts have been
      extensively studied in man and mice. One major action is their ability to trigger
      production of massive amounts of interferon-alpha (IFN-alpha) by plasmacytoid
      dendritic cells (PDC), also referred to as natural IFN-alpha/beta producing cells
      (NIPC). The present study using porcine PBMC activated by CpG-ODN or plasmid DNA
      revealed a considerable variation in the IFN-alpha production in response to
      various CpG-ODN constructs. Several phosphodiester ODNs, such as 5'
      TTTTCAATTCGAAGATGAAT 3' (ODN H), and the plasmid pcDNA3 all required pre
      incubation with lipofectin in order to induce IFN-alpha. Intact unmethylated CpGs
      were also important, because methylation or substitution of the cytosines and CpG
      inversion strongly reduced the IFN-alpha induction by single- or double-stranded
      forms of ODN H. Certain CpG-ODNs that contained flanking phosphorothioate or
      phosphodiester poly-G sequences were potent inducers of IFN-alpha without pre
      incubation with lipofectin, for instance the ODN 2216 (5' GGGGGACGATCGTCGGGGGG
      3'). While poly-G sequences have been suggested to increase uptake of ODNs by
      cells, they did not obviate the need for lipofectin when added to the ODN H.
      However, they resulted in up to five-fold increases of the IFN-alpha levels
      caused by ODN H upon lipofection, indicating other enhancing effects of poly-G
      sequences on the induction of IFN-alpha. The identity of the IFN-alpha producing
      cells (IPC) stimulated by CpG-ODN or plasmid DNA was studied by means of flow
      cytometry using combined staining for intracellular IFN-alpha and surface
      markers. Approximately 1-3 IPC/10(3) PBMC were detected, compared to only 3
      IPC/10(4) PBMC stimulated by Aujeszky's disease virus. The IPC frequencies were
      confirmed by detection of IFN-alpha mRNA positive cells by in situ hybridisation.
      The IPC induced by CpG-ODN or plasmid DNA had a similar phenotype, expressing CD2
      and CD4 and intermediate levels of MHC class II and the myeloid marker SWC3, but
      not the markers of T and B cells or monocytes (CD3, CD21 and CD14). Consequently,
      porcine IPC that respond to CpG-DNA seem to correspond to the PDC/NIPC.

PMID- 15261696
TI  - Age related changes in humoral immune response of hybrid striped bass (Morone
      chrysops x Morone saxatilis).
AB  - A number of factors can influence immune function affecting the magnitude and
      duration of specific immune responses. One factor which has been noted to affect
      immune responses is age of animal. In mammals, juveniles have a lower immune
      response when compared to adults. In fish, fry have a lower immune response than
      adults; however, few studies have investigated the immune response in juveniles,
      the age when most fish are reared in aquaculture settings. The humoral immune
      responses of hybrid striped bass (Morone saxatilis x Morone chrysops) at five
      different ages were compared to determine any maturational changes. Fifty fish
      were bath immunized with a commercial Vibrio vaccine at 4, 6, 9, 15, and 19
      months of age. The antibody response in these fish was monitored by an enzyme
      linked immunosorbent assay (ELISA) for 106 days post-vaccination. The magnitude,
      duration, and time to peak level were compared to controls and between the
      different ages using analysis of variance (ANOVA). Younger fish exhibited
      significantly lower antibody levels indicating that juvenile fish may not be able
      to mount as effective an immune response as young adult fish.

PMID- 15261697
TI  - Measurement of phagocytosis and oxidative burst of canine neutrophils: high
      variation in healthy dogs.
AB  - Quantitative analysis of phagocytosis and oxidative burst in canine
      polymorphonuclear (PMN) cells was performed by flow cytometry techniques.
      Different concentrations of phorbol myristate acetate (PMA) were used to modulate
      PMN phagocytosis. A low concentration of PMA (3 nmol) resulted in increased
      phagocytic activity of canine PMN, which could not be enhanced by higher dosages.
      Experiments with a reference cell population showed high losses of PMN, most
      probably by adherence to plastic material. It was possible to avoid this loss by
      layering all ingredients on cushions of Histopaque. However, Histopaque had a
      negative influence on the phagocytic activity of canine PMN. The use of PMA led
      to a dosage-dependent increase in the oxidative burst measured by the production
      of reactive oxygen species (ROS). Cushions of Histopaque were used to avoid cell
      loss. There was no negative influence of Histopaque on ROS formation. Storage of
      canine PMN for 24 h at room temperature had no negative influence on phagocytosis
      or oxidative burst measurements. Variations in the ROS assays conducted by two
      different examiners could be eliminated by use of a Histopaque-cushion.

PMID- 15261698
TI  - Impairment of oxidative burst in porcine neutrophils induced by pseudorabies
      virus.
AB  - Industrial swine production is affected by several serious viral diseases, such
      as pseudorabies, hog cholera, porcine reproductive and respiratory syndrome,
      which are frequently complicated with the increased incidence of bacterial
      complications such as Actinobacillus pleuropneumoniae (APP). This clinical
      observation is suggestive of a virus-bacteria synergism on the pathogenesis. One
      hypothesis is that viruses induce polymorphonuclear cell (PMNs, primarily
      neutrophils) dysfunction resulting in defective antibacterial resistance. The
      purpose of this study was to use the pseudorabies virus (PrV) as a model to
      explore the possibility of virus-induced PMN dysfunctions in pigs. The goals were
      to evaluate, in ex vivo settings, the oxidative burst (OB) function of pig PMNs,
      and to evaluate whether PrV could affect these responses to APP. We found that
      PrV served as a mild OB stimulant (2-fold) to pig PMNs, which also launched a
      significant burst to phorbol 12-myristate 13-diacetate (PMA; 61-fold), to non
      opsonized, heat-killed and formaldehyde-fixed APP (8-fold), and to normal pig
      serum-opsonized APP (34-fold). Interestingly, the PMA-induced OB could be reduced
      50-70% by preincubating PMNs with PrV, and the critical target was not likely the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase itself. Inactivated
      PrV was as efficient as viable PrV at exerting the inhibitory effect. On the
      other hand, PrV exerted a primarily additive effect on APP-induced OB, when the
      cytotoxic effect of APP on PMNs was avoided. The current finding suggests the
      possibility that activated PMNs are susceptible to PrV-induced dysfunction, and
      that the PrV-APP synergism may require upstream stimuli of PMNs to be initiated.

PMID- 15261699
TI  - Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive
      dyskinesia in patients with schizophrenia.
AB  - Several lines of evidence suggest that tardive dyskinesia (TD) may be associated
      with altered dopaminergic neurotransmission. We hypothesized that deranged
      dopamine degradation enzyme activities might be related to the susceptibility to
      TD through altered dopaminergic neurotransmission in the central nervous system.
      In the present study, we investigated the relationship between the gene
      polymorphisms of three dopamine degradation enzymes and TD. We genotyped the
      valine/methionine polymorphism of codon 108/158 in the catechol-O
      methyltransferase (COMT) gene, the 30-bp repeat polymorphism in the promoter of
      the monoamine oxidase A (MAOA) gene, and the A/G polymorphism in intron 13 of the
      monoamine oxidase B (MAOB) gene in 206 Japanese patients with schizophrenia. No
      significant difference was found in total scores on the Abnormal Involuntary
      Movement Scale (AIMS) among the subject groups, sorted according to the COMT,
      MAOA and MAOB genotypes. Moreover, no significant difference was found in allele
      frequencies between patients with TD and patients without TD for any of the
      polymorphisms. As both COMT and MAO genes are involved in degrading
      catecholamines, we also sought evidence for additive and epistatic effects, but
      none was observed. Our data, therefore, do not support the hypothesis that
      polymorphisms in COMT, MAOA, and MAOB genes are involved individually or in
      combination in the predisposition to TD.

PMID- 15261700
TI  - Transcranial magnetic stimulation for auditory hallucinations in schizophrenia.
AB  - It has been suggested that low frequency transcranial magnetic stimulation (TMS)
      over left temporo-parietal cortex may reduce the frequency and intensity of
      auditory hallucinations in schizophrenia. Sixteen patients with hallucinations,
      treatment-resistant for at least 2 months, were randomised into a placebo
      controlled crossover study of TMS at 1 Hz and 80% of motor threshold over left
      temporo-parietal cortex. Treatment periods lasted for 4 days, with daily duration
      escalating from 4 to 8, 12 and 16 min on subsequent days. Each minute of
      stimulation was followed by 15 s of rest to check coil position and allow the
      patient to move, if necessary. Both patients and symptom raters were unaware of
      the treatment condition. Patients' hallucination scores improved from baseline
      with both real and sham TMS, and there was no significant difference between real
      and sham treatments. There was a trend for second treatments, whether sham or
      real, to be more effective than first treatments. Other psychopathology scales
      (apart from positive symptoms) and verbal memory were not affected by real or
      sham TMS. Previous positive studies could not be replicated with these
      parameters. TMS is safe if applied within the protocol used.

PMID- 15261701
TI  - Regulation of central dopamine-2 receptor sensitivity by a proportional control
      thermostat in humans.
AB  - Central dopamine-2 (D2) receptors are importantly involved in the pathogenesis
      and treatment of schizophrenia. Central D2 receptors are also involved in
      thermoregulation. Recently, a type of central nervous system proportional control
      thermostat was described that governs the magnitude of several serotonin receptor
      mediated core body thermoregulatory responses in proportion to both the amount of
      nocturnal melatonin secreted and the minimum level of nocturnal core body
      temperature (Tmin). The present study investigated whether the magnitude of D2
      receptor-mediated hypothermia--a putative index of central D2 receptor
      sensitivity--is also regulated by this proportional control thermostat in humans.
      Twenty healthy subjects had their 02:00 h melatonin concentrations (MT2am) and
      Tmin measured during consecutive sleep episodes and their core body temperature
      responses (TAUC) measured the next two mornings after oral ingestion of either
      the D2 receptor agonist bromocriptine 3.125 mg or placebo. We found that the
      bromocriptine-induced TAUC was significantly and independently correlated with
      both Tmin and MT2am. In conclusion, D2 receptor-mediated hypothermia, an index of
      central D2 receptor sensitivity, is regulated by a proportional control
      thermostat in humans. The abnormal D2 receptor function in schizophrenia could be
      related to dysfunction of this thermostat.

PMID- 15261702
TI  - Electroretinography in patients with winter seasonal affective disorder.
AB  - A retinal sensitivity abnormality has been hypothesized in seasonal affective
      disorder (SAD). To explore this hypothesis, the electroretinogram (ERG) was used
      to assess retinal sensitivity at the level of the rod photoreceptor system. We
      examined 27 depressed patients who met DSM-III-R criteria for major depression,
      recurrent, with a seasonal (winter) pattern and 23 normal control subjects who
      were age-paired and sex-matched as much as possible with the SAD patients. ERG
      testing was performed in dark-adapted, dilated eyes in winter between 10:00 and
      15:00 h. Retinal sensitivity was based on the light stimulus intensity necessary
      to reach a 50-microV amplitude threshold. We found that retinal sensitivity was
      significantly lower (0.21 log units) in SAD patients compared with normal control
      subjects and that 55% of the patients had a retinal sensitivity value one
      standard deviation lower than the mean value of the control subjects. These
      results are consistent with a retinal hyposensitivity hypothesis for SAD, but the
      explanation for lower rod photoreceptor sensitivity in SAD is not known. We
      hypothesize that brain neurotransmitter dysregulation may be at the origin of
      both the mood disorder and retinal sensitivity change.

PMID- 15261703
TI  - Posttraumatic stress disorder among professional and non-professional rescuers
      involved in an earthquake in Taiwan.
AB  - This study investigated the prevalence of posttraumatic stress disorder (PTSD)
      among professional and non-professional rescue workers involved in the 1999 Chi
      Chi Earthquake in Taiwan. One month following the disaster, 252 rescue workers
      (167 professional rescue workers, 85 non-professional volunteers) were surveyed
      with the Chinese version of the Davidson Trauma Scale (DTS-C) and the Chinese
      version of the SPAN (SPAN-C). Non-professional rescuers had significantly higher
      scores than professional rescuers on both the DTS-C and the SPAN-C. The
      prevalences of PTSD, as defined by a DTS-C score > or = 44, among professional
      and non-professional rescuers were 19.8% and 31.8%, respectively. Among the three
      subscales of the DTS-C, only scores on the numbness/avoidance subscale were
      significantly higher in the non-professional than in the professional rescue
      workers. The results of this study suggest that disaster rescue work is
      associated with a high level of stress even for highly trained professionals and
      may lead to mental health problems.

PMID- 15261704
TI  - Face to face: visual scanpath evidence for abnormal processing of facial
      expressions in social phobia.
AB  - Cognitive models of social phobia propose that cognitive biases and fears
      regarding negative evaluation by others result in preferential attention to
      interpersonal sources of threat. These fears may account for the hypervigilance
      and avoidance of eye contact commonly reported by clinicians. This study provides
      the first objective examination of threat-related processing in social phobia. It
      was predicted that hyperscanning (hypervigilance) and eye avoidance would be most
      apparent in social phobia for overt expressions of threat. An infrared corneal
      reflection technique was used to record visual scanpaths in response to angry,
      sad, and happy vs. neutral facial expressions. Twenty-two subjects with social
      phobia were compared with age- and sex-matched normal controls. As predicted,
      social phobia subjects displayed hyperscanning, (increased scanpath length) and
      avoidance (reduced foveal fixations) of the eyes, particularly evident for angry
      faces. The results could not be explained by either medication or co-morbid
      depression. These findings are consistent with theories emphasising the role of
      information processing biases in social phobia, and show promise in the
      application to treatment evaluation in this disorder.

PMID- 15261705
TI  - Effect of mental and physical stress on platelet activation markers in depressed
      patients and healthy subjects: a pilot study.
AB  - Depression represents an independent risk factor for developing ischemic heart
      disease, with platelet hyperactivity possibly serving as an important mediator of
      this association. In this pilot study we analyzed platelet surface activation
      markers in response to two stimuli, mental stress and physical activity. Using
      flow cytometry, we quantified the presence of two functional activation-dependent
      glycoprotein receptors on platelets' surface (P-selectin, GP53). Platelet
      reactivity was assessed as the difference in markers' fluorescence intensity
      before and after stimulation. We included 10 depressed psychiatric inpatients and
      10 age- and sex-matched healthy subjects in our study. There was a significant
      rise in platelet activation markers in both groups associated with the stress
      protocol. When the effect of stressors was analyzed separately, strenuous
      physical activity was found to lead to a significant rise in platelet activation
      markers in depressed patients but not in healthy subjects, although values
      indicated a higher baseline level of activation in healthy subjects. These
      preliminary results lend partial support to the hypothesis of an exaggerated
      platelet reactivity after physical activity in depression, thus possibly
      contributing to an increased cardiovascular risk in this disorder.

PMID- 15261706
TI  - Symptomatological and cognitive predictors of insight in chronic schizophrenia.
AB  - Studies of schizophrenia show lack of agreement about the relationship of
      symptomatological and cognitive factors to insight. In this study, positive and
      negative symptomatology and cognitive function were assessed by the Positive and
      Negative Syndrome Scale (PANSS), the Wisconsin Card Sorting Test (WCST), and the
      Wechsler Adult Intelligence Scale Revised (WAIS-R) in male chronic schizophrenic
      patients in relation to level of insight measured with the Japanese version of
      the Schedule for the Assessment of Insight (SAI-J). Negative symptoms were
      significantly and negatively associated with overall insight, particularly with
      treatment compliance and recognition of mental illness. The present findings
      suggest that aspects of insight such as treatment compliance and recognition of
      mental illness are negatively associated with negative symptoms.

PMID- 15261707
TI  - Predictors of improved mood over time in clinical trials for major depression.
AB  - The objective of this exploratory analysis was to use a repeated measures
      modeling approach to identify potential predictors of improved mood over time in
      patients with major depression. Fifty-one subjects with major depressive disorder
      (MDD) were enrolled in a 1-week single blind placebo lead-in, followed by an 8
      week, double-blind placebo-controlled treatment with either fluoxetine or
      venlafaxine. Hierarchical linear regression models were used to identify baseline
      and placebo lead-in predictors of change in repeated measures of the Hamilton
      Depression Rating Scale (HDRS) during treatment. Non-specific predictors of
      improved mood included decreased prefrontal activity during placebo lead-in as
      measured by quantitative electroencephalographic cordance, lower pretreatment
      depressed mood on the HDRS, shorter duration of current episode, increased
      verbalization of suicidal thoughts, no family history of mood disorders, less
      severe middle insomnia, higher guilt, lower somatic anxiety, and younger age.
      Moderators of improved mood included somatization, paranoid ideation, and self
      reported depressed mood. We also found that change in prefrontal cordance after
      randomization mediated the effects of middle insomnia, suicidal thoughts, and
      family history of mood disorders. We recommend the use of repeated measures
      modeling, and the exploration of relationships among biological and psychological
      factors, for future analyses of clinical trial data.

PMID- 15261708
TI  - Depressive syndrome in major psychoses: a study on 1351 subjects.
AB  - The aim of this study was to investigate depressive symptomatology across
      distinct major psychiatric disorders. A total of 1351 subjects affected by major
      depressive disorder (MDD = 389), bipolar disorder (BP = 511), delusional disorder
      (DD = 93) and schizophrenia (SKZ = 358) were included in our study. Subjects were
      assessed using the Operational Criteria for Psychotic Illness checklist (OPCRIT).
      The most frequently represented depressive symptoms in MDD were Loss of
      energy/tiredness, Loss of pleasure, Poor concentration, and Sleep disorders.
      Compared with MDD, BP had higher occurrences of Agitated activity, Excessive
      sleep, and Increased appetite and/or Weight gain, as well as lower Loss of
      pleasure. In our sample, 32.3% and 26.8% of DD and SKZ, respectively, had quite
      consistent depressive symptomatology, with at least four or more depressive
      symptoms. The most common depressive symptoms were Sleep disorders, Poor
      concentration and Loss of energy/Tiredness, followed by Psychomotor symptoms in
      SKZ only. Excessive self-reproach, Suicidal ideation, and Appetite and/or Weight
      changes were more specific to mood disorders. Finally, compared with SKZ, DD
      suffered from more depressive symptoms and had more severe depressive
      symptomatology. A quite consistent level of depressive symptomatology is
      therefore present in subpopulations of delusional and schizophrenic subjects
      other than in affective subjects. We identified some symptoms that are common
      across all major psychoses and symptoms that are more specific to each group.

PMID- 15261709
TI  - Dimensions of major psychoses: a confirmatory factor analysis of six competing
      models.
AB  - The symptoms of major psychosis aggregate in factors. Models of one to eight
      dimensions have been reported. In the present study, we tested six competing
      factor models, based on the psychotic and affective items of the OPCRIT
      checklist, in a large sample (N = 1294) of patients diagnosed with DSM-IV
      schizophrenia (n = 460), bipolar disorder (n = 726) and delusional disorder (n =
      108). Confirmatory factor analysis was used to test the following models: (1)
      unique psychotic dimension; (2) positive-manic items, negative-depressive items;
      (3) model 2 with the addition of a disorganized factor; (4A) positive, negative,
      depressive and manic dimensions; (4B) model 4A with loss of pleasure (Anhedonia)
      and loss of energy (Apathy) included among depressive instead of negative
      symptoms; and (5) same as model 4B except for the addition of a disorganized
      domain. The four- and five-factor models fit the data much better than simpler
      ones. Between the two four-factor models, M4B emerged as more appropriate than
      M4A. The five-factor solution (M5) displayed the best fit. In conclusion, our
      confirmatory factor analysis in a large sample of psychotic subjects indicated
      that the symptomatology of major psychoses is composed of the following five
      factors: mania, positive symptoms, disorganization, depression and negative
      symptoms.

PMID- 15261710
TI  - Anxious-retarded depression: relation to family history of depression.
AB  - Anxious-retarded depression is a two-dimensionally defined subcategory of
      depression based on high scores for both anxiety and retardation. The anxious
      retarded subcategory is related to melancholia as defined by DSM-IV. Patients
      with this diagnosis exhibit elevated plasma arginine vasopressin (AVP) and a high
      correlation between plasma vasopressin and cortisol, which suggests
      vasopressinergic overactivation of the hypothalamus-pituitary-adrenal (HPA) axis.
      In this report, we present the multidimensional derivation of the anxious
      retarded subcategory from DSM-IV melancholia, and a second step in the validation
      of this anxious-retarded subcategory by exploring its relation to family history
      of depression. The patient sample comprised 89 patients with major depression and
      encompassed 66 patients investigated previously regarding plasma AVP and
      cortisol. All patients were rated for the following three dimensions of
      psychopathology: autonomic dysregulation (anxiety), motivational inhibition
      (retardation), and emotional dysregulation, as well as for family history of
      depression. The dependence of DSM-IV melancholia on the sum scores and the
      dichotomized scores on the three dimensions was investigated by multiple logistic
      regression. Thereafter, the dependence of the family history for depression on
      the same parameters was also investigated. The melancholic subcategory depended
      on the interaction between the sum scores, as well as on the interaction between
      the dichotomized scores for anxiety and retardation that constitute the anxious
      retarded subcategory. Family history for depression depended only on the
      interaction of the dichotomized scores, and thus on the anxious-retarded
      subcategory.

PMID- 15261711
TI  - Concordance of DSM-IV Axis I and II diagnoses by personal and informant's
      interview.
AB  - The validity and reliability of using psychological autopsies to diagnose a
      psychiatric disorder is a critical issue. Therefore, interrater and test-retest
      reliability of the Structured Clinical Interview for DSM-IV Axis I and
      Personality Disorders and the usefulness of these instruments for the
      psychological autopsy method were investigated. Diagnoses by informant's
      interview were compared with diagnoses generated by a personal interview of 35
      persons. Interrater reliability and test-retest reliability were assessed in 33
      and 29 persons, respectively. Chi-square analysis, kappa and intraclass
      correlation coefficients, and Kendall's tau were used to determine agreement of
      diagnoses. Kappa coefficients were above 0.84 for substance-related disorders,
      mood disorders, and anxiety and adjustment disorders, and above 0.65 for Axis II
      disorders for interrater and test-retest reliability. Agreement by personal and
      relative's interview generated kappa coefficients above 0.79 for most Axis I and
      above 0.65 for most personality disorder diagnoses; Kendall's tau for dimensional
      individual personality disorder scores ranged from 0.22 to 0.72. Despite of a
      small number of psychiatric disorders in the selected population, the present
      results provide support for the validity of most diagnoses obtained through the
      best-estimate method using the Structured Clinical Interview for DSM-IV Axis I
      and Personality Disorders. This instrument can be recommended as a tool for the
      psychological autopsy procedure in post-mortem research.

PMID- 15261712
TI  - Development of the Brief Bipolar Disorder Symptom Scale for patients with bipolar
      disorder.
AB  - The Brief Bipolar Disorder Symptom Scale (BDSS) is a 10-item measure of symptom
      severity that was derived from the 24-item Brief Psychiatric Rating Scale
      (BPRS24). It was developed for clinical use in settings where systematic
      evaluation is desired within the constraints of a brief visit. The psychometric
      properties of the BDSS were evaluated in 409 adult outpatients recruited from 19
      clinics within the public mental health system of Texas, as part of the Texas
      Medication Algorithm Project (TMAP). The selection process for individual items
      is discussed in detail, and was based on multiple analyses, including principal
      components analysis with varimax rotation. Selection of the final items
      considered the statistical strength and factor loading of items within each of
      those factors as well as the need for comprehensive coverage of critical symptoms
      of bipolar disorder. The BDSS demonstrated good psychometric properties in this
      preliminary investigation. It demonstrated a strong association with the BPRS24
      and performed similarly to the BPRS24 in its relationship to other symptom
      measures. The BDSS demonstrated superior sensitivity to symptom change, and an
      excellent level of agreement for classification of patients as either responders
      or non-responders with the BPRS24.

PMID- 15261713
TI  - The Rater Applied Performance Scale: development and reliability.
AB  - Previous studies of rater performance and interrater reliability have used
      passive scoring tasks such as rating patients from a videotaped interview. Little
      is known, however, about how well raters conduct assessments on real patients or
      how reliably they apply scoring criteria during actual assessment sessions. With
      growing recognition of the importance of monitoring and review of actual
      evaluation sessions, there is need for a systematic approach to quantify raters'
      applied performance. The Rater Applied Performance Scale (RAPS) measures six
      dimensions of rater performance (adherence, follow-up, clarification, neutrality,
      rapport, and accuracy) based on reviews of audiotaped or videotaped assessment
      sessions or on live monitoring of assessment sessions. We tested this new scale
      by having two reviewers rate 20 Hamilton Depression Scale rating sessions
      ascertained from a multi-site depression trial. We found good internal
      consistency for the RAPS. Interrater (i.e. inter-reviewer) reliability was
      satisfactory for RAPS total score ratings. In addition, RAPS ratings correlated
      with quantitative measures of scoring accuracy based on independent expert
      ratings. Preliminary psychometric data suggest that the RAPS may be a valuable
      tool for quantifying the performance of clinical raters. Potential applications
      of the RAPS are considered.

PMID- 15261715
TI  - Impairment in visual and spatial perception in schizophrenia and delusional
      disorder.
AB  - The Judgment of Line Orientation Test, a visuospatial processing task, was
      administered to normal subjects, to schizophrenic patients and to patients with
      delusional disorder. Significantly better performance was seen in the normal
      subjects than in the schizophrenic and delusional patients. Delusional patients,
      in turn, showed better performance than the schizophrenic patients.

PMID- 15261714
TI  - Analysis of SYNJ1, a candidate gene for 21q22 linked bipolar disorder: a
      replication study.
AB  - Linkage analysis has shown that chromosome 21q22 may contain a candidate gene for
      bipolar disorder (BPD). One potential 21q22 candidate gene we previously analyzed
      is SYNJ1, which encodes synaptojanin 1, an inositol 5-phosphatase. Previous
      mutation screening of SYNJ1 identified three rare functional variants, one of
      which is a polymorphic variant near the intron 12-oxon 12 border. The rare
      variants were found only in a total of four BPD patients and no controls, and a
      trend toward significance was found for the intron 12 polymorphism. In an
      analysis of a new set of 84 bipolar patients, none of the rare variants were
      detected. There was an increase in allele 2 for the intron 12 polymorphism,
      similar to our original study, but the result was not significant. The combined
      data from both studies continue to show a trend toward significance for allele 2
      homozygotes in BPD.

PMID- 15261717
TI  - Immunotoxicological response of the earthworm Lumbricus terrestris following
      exposure to cement kiln dusts.
AB  - Cement kiln dusts are made of a complex mixture of elements. We have evaluated
      the potential negative impact of those dusts on the immune system of the
      earthworm Lumbricus terrestris. We specifically studied cell viability and
      phagocytic activity of coelomocytes extruded during electrical stimulation. We
      used two modes of exposures: in vitro, and soil incubation using OECD artificial
      soil media. Extruded coelomocytes were exposed 18 h in vitro to 10, 100, and 500
      mg L(-1) of cement kiln dust particles. The phagocytosis and the cell viability
      were determined using a double-laser-flow acquisition cytometry system. Using the
      double laser allows us to use a dichlorofluorescein diacetate (DCFDA) marker to
      discriminate the biological cells from the cement kiln dusts. Dead cells are
      marked using propidium iodide (PI). All three exposure levels showed highly
      significant impacts on cell viability and phagocytic activity. The in vivo soil
      incubation was performed using 10, 100, and 1000 mg kg(-1) of cement kiln dusts
      incorporated into the OECD media. Here, to discriminate the biological cells from
      the mineral dusts we only needed to use PI. The day-to-day variability of the in
      vivo assay was high and although we can observe an overall reduction in cell
      viability at the highest concentration tested, no statistically significant
      effects could be observed on either cell viability or phagocytosis.

PMID- 15261716
TI  - Modeling impacts on populations: fathead minnow (Pimephales promelas) exposure to
      the endocrine disruptor 17beta-trenbolone as a case study.
AB  - Evaluation of population-level impacts is critical to credible ecological risk
      assessments. In this study, a predictive model was developed to translate changes
      in fecundity of the fathead minnow (Pimephales promelas) in a short-term
      laboratory toxicity test to alterations in population growth rate. The model
      uniquely combines a Leslie population projection matrix and the logistic
      equation. Application of the model requires only a life table for the organism of
      interest, a measure of carrying capacity for the given population, and an
      estimation of the effect of a stressor on vital rates. The model was applied to
      investigate population dynamics for fathead minnow exposed to the androgen
      receptor agonist 17beta-trenbolone. Organismal-level responses for fathead
      minnows exposed to varying levels of 17beta-trenbolone were used to determine
      projected alterations in a population existing in a small body of water
      containing varying concentrations of the androgen. Fathead minnow populations
      occurring at carrying capacity and subsequently exposed to 0.027 microg/L of
      17beta-trenbolone exhibited a 51% projected decrease in average population size
      after 2 years of exposure. Populations at carrying capacity exposed to
      concentrations of 17beta-trenbolone > or = 0.266 microg/L exhibited a 93%
      projected decrease in average population size after 2 years of exposure. Overall,
      fathead minnow populations exposed to continued concentrations of 17beta
      trenbolone equal to or greater than 0.027 microg/L were projected to have average
      equilibrium population sizes that approached zero.

PMID- 15261718
TI  - A new ultrasound protocol for extrusion of coelomocyte cells from the earthworm
      Eisenia fetida.
AB  - There is mounting evidence that earthworms could be used as a sentinel species
      for soil ecotoxicity evaluation. In this aspect, phagocytosis by coelomocytes was
      shown to be a sensitive biomarker of exposure to xenobiotics. In this paper, we
      introduce a simple method for ultrasound extrusion of earthworm coelomocytes that
      generates a high cell yield, does not interfere with phagocytic competence, and
      requires a minimum of manipulations. Coelomocytes were extruded from the
      earthworm Eisenia fetida using this new ultrasound method and compared with
      ethanol and electrical extrusion. The ultrasonic extrusion showed the highest
      cell recovery with 3.17 +/ -0.8 x 10(6) cells per earthworm compared with 2.22 +/
      0.8 x 10(6) cells per earthworm for electrical extrusion and 1.57 +/- 0.07 x
      10(6) cells per earthworm for ethanol extrusion. No significant differences in
      the cell viability were observed using propidium iodide and flow cytometry with
      viability for extrusion with ethanol of 63.8 +/- 12.7%, electrical 76.8 +/- 7.5%,
      and ultrasound 68.2 +/- 7.8%. To compare the potential effect of extrusion on
      cell quality, the cells extruded using the three methods were subjected to an 18
      h in vitro exposure to methylmercury chloride (MeHgCl; CH3HgCl) with
      concentrations ranging from 10(-9) to 10(-4)M. The half-maximal effective
      concentration (EC50) for inhibition of phagocytosis occurred between 10(-7) and
      10(-6)M. We found no significant differences among the extrusion methods for the
      phagocytic potential of the coelomocytes. This method does not harm the worms and
      can certainly improve collection of coelomocytes from earthworms and therefore
      contribute to the development of bioassays using invertebrates.

PMID- 15261719
TI  - A nonlinear model of stress hormone levels in rats-the interaction between
      pollution and parasites.
AB  - The impact of an infection with a parasite and a simultaneous cadmium exposure on
      the stress hormone levels of rats was studied. To this end, we introduce a
      nonlinear heteroscedastic model, which is able to describe the temporal evolution
      of cortisol concentrations in groups of rats treated by cadmium or parasite
      infection. A thorough analysis gives strong evidence that parasitic infection and
      cadmium exposure affect the stress hormone level of rats in an additive manner.
      Therefore, the host's response to environmental pollution should be studied in
      relation to parasite infections.

PMID- 15261720
TI  - Field application of autometallography and X-ray microanalysis using the
      digestive gland of the common mussel.
AB  - The histological and ultrastructural localization of heavy metals in the
      digestive gland of the mussel, Mytilus galloprovincialis, was evaluated using
      autometallography and X-ray microanalysis on epoxy resin sections. Mussels were
      collected from two populations along Thermaikos gulf (port of Thessaloniki and
      Halastra) and one population in Strymonikos Gulf (Olympiada). With the use of
      autometallography, the light and electron microscopic observations indicated that
      in the digestive gland, the metals are localized in lysosomal structures, such as
      heterolysosomes and the residual bodies of digestive cells. Through both
      techniques, mussels collected from the port of Thessaloniki displayed
      concentrations of metals higher than those recorded in mussels from Halastra and
      Olympiada. This fact is consistent with other reports indicating a similar
      distribution of metals in Thermaikos Gulf and Strymonikos Gulf. The results of
      the study support the use of both techniques, autometallography and X-ray
      microanalysis, as a suite of stress indices for pollution biomonitoring studies.

PMID- 15261721
TI  - Using factorial experiments to study the toxicity of metal mixtures.
AB  - Two-level factorial experiments were employed in this study for understanding and
      predicting the toxicity of binary and ternary metal mixtures. Toxicity of metal
      mixtures with concentrations between the respective EC10 and EC80 values was
      experimentally measured. Models were fit to the experimental data and the
      resultant models were of high quality as reflected by R2 (coefficient of
      determination). Interactions between mixture components were indicated by the
      existence of statistically significant interaction terms in the models. Toxicity
      predictions based on the models were compared with observed toxicity for binary
      and ternary metal mixtures. The models developed did not assume additivity
      between metals, were simple and interpretable, and gave satisfactory predictions
      of the toxicity of metal mixtures in aqueous solutions without requiring
      knowledge on synergism or antagonism.

PMID- 15261722
TI  - Aquatic selenium pollution is a global environmental safety issue.
AB  - Selenium pollution is a worldwide phenomenon and is associated with a broad
      spectrum of human activities, ranging from the most basic agricultural practices
      to the most high-tech industrial processes. Consequently, selenium contamination
      of aquatic habitats can take place in urban, suburban, and rural settings alike-
      from mountains to plains, from deserts to rainforests, and from the Arctic to the
      tropics. Human activities that increase waterborne concentrations of selenium are
      on the rise and the threat of widespread impacts to aquatic life is greater than
      ever before. Important sources of selenium contamination in aquatic habitats are
      often overlooked by environmental biologists and ecological risk assessors due to
      preoccupation with other, higher priority pollutants, yet selenium may pose the
      most serious long-term risk to aquatic habitats and fishery resources. Failure to
      include selenium in the list of constituents measured in contaminant
      screening/monitoring programs is a major mistake, both from the hazard assessment
      aspect and from the pollution control aspect. Once selenium contamination begins,
      a cascade of bioaccumulation events is set into motion which makes meaningful
      intervention nearly impossible. However, this cascade of events need not happen
      if adequate foresight and planning are exercised. Early evaluation and action are
      key. Prudent risk management based on environmentally sound hazard assessment and
      water quality goals can prevent biological impacts.

PMID- 15261723
TI  - Piranhas (Serrasalmus spp.) as markers of mercury bioaccumulation in Amazonian
      ecosystems.
AB  - Mercury (Hg) concentration in fish depends on feeding strategies and age/size
      within the species as well as on water parameters related to acidity and Hg
      speciation. We chose two species of piranhas (Serrasalmus aff. eigenmanni and
      Serrasalmus rhombeus) to test their suitability as markers of Hg bioaccumulation.
      The results of Hg concentrations in piranhas of the Rio Negro, with no history of
      gold-mining activity, are similar to other Amazonian rivers with intensive gold
      mining. An increase in water Hg associated with low pH favored higher mean Hg
      concentrations in the two species. S. rhombeus in this habitat showed a
      consistently higher Hg concentration than S. eigenmanni. This result was
      attributed to fish size because of differences in correlation coefficient between
      S. rhombeus (r = 0.4443; P < 0.0001) and S. eigenmanni (r = 0.1520; P = 0.0135).
      Matching for fish weight resulted in comparable ranges of Hg concentrations
      between the two species.

PMID- 15261724
TI  - Toxic metals in aquatic plants surviving in surface water polluted by copper
      mining industry.
AB  - Concentrations of the metals Al, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn,
      as well as the macronutrients N, P, K, Ca, Mg, and S were measured in water,
      sediments, and the aquatic macrophytes Potamogeton pectinatus and Myriophyllum
      spicatum, growing in surface water receiving sewages and solid wastes from a
      copper smelter and a copper ore processing factory located in the Legnica-Glogow
      copper district in Southwest Poland. The deposition of mineral wastes in this
      area belong to the largest repository in Europe. The plants were able to survive
      at heavily contaminated sites. The concentrations of Cd (up to 0.6-1.7 microg/L
      in water and up to 10.1-12.9 mg/kg in sediments), Cu (up to 29-48 microg/L in
      water and up to 4.6-5.6g/kg in sediments), Pb (up to 1.5-2.2 g/kg in sediments),
      and Zn (up to 167-200 microg/L in water and up to 1.4-1.8 g/kg in sediments)
      seriously exceeded background values. P. pectinatus was able to survive tissue
      concentrations (in mg/kg) of up to 920 Cu, 6240 Mn, 98 Co, and 59 Ni, while M.
      spicatum survived tissue concentrations up to 1040 Cu, 6660 Mn, and 57 Co for.
      Enrichment ratios of elements in plant tissue and in water were much higher than
      those between plant tissue and sediments.

PMID- 15261725
TI  - Effect of a low dose of aluminum on mitotic and meiotic activity, 4C DNA content,
      and pollen sterility in rice, Oryza sativa L. cv. Lalat.
AB  - Aluminum toxicity in acidic soils poses a major threat to plant growth and
      development. The effects of a low dose of aluminum (50 microM, AlCl3) on various
      cytological parameters, including mitotic and meiotic chromosomal divisions, in
      situ nuclear DNA content, interphase nuclear volume (INV), and pollen fertility
      were compared in untreated (controls) and treated rice plants (Oryza sativa cv.
      Lalat). The results showed varied chromosomal abnormalities, including chromosome
      stickiness, laggards, sticky bridge, occurrence of micronuclei, as well as
      binucleate and multinucleated cells, as a result of aluminum treatment. Aluminum
      toxicity also inhibited to a small extent the growth of the rice cultivar Lalat.
      The mitotic and meiotic indexes, even after a prolonged period of recovery, were
      significantly low. The chromosomal anomalies in the meiotic cells persisted, and
      plants exhibited a high percentage of pollen sterility (approximately 64%). The
      nuclear DNA content declined markedly from 11.85 pg in the control to 6.30 pg in
      the treated plants. The INV also varied significantly between the untreated
      (controls) and the treated plants. The occurrences of different types of
      chromosomal aberrations, reduction in the amount of nuclear DNA, and persistence
      of the phytotoxic effects at the post-treatment stage suggest carcinogenic
      effects of aluminum on rice plants. The presence of aluminum in acidic soils
      might thus be extremely hazardous and might cause permanent cytotoxic disorder in
      rice plants.

PMID- 15261726
TI  - Identification of pollution sources by means of moss bags.
AB  - Moss bags containing Scleropodium purum were exposed for 30 days in an industrial
      area in which a chlor-alkali plant (CAP) and a concrete factory (CF) are located
      close to one another (121 m). Following the exposure, the transplanted mosses
      were analyzed to determine levels of Hg, Zn, Ni, and Cr. The enrichment factors
      (EFs) of the metals (final concentration/initial concentration) were calculated;
      the mean values obtained were 26.4 for Hg, 6.6 for Zn, 1.07 for Ni, and 1.0 for
      Cr. Dispersion of Cr and Ni was closely related, probably because they were
      dispersed together on the same particle. The spatial structure of the data was
      examined, and significant fits to the semivariograms were found for Hg, Zn, and
      Cr, using kriging to interpolate the data. Using this technique, it was possible
      to estimate where the maximum concentrations of elements occurred, allowing us to
      distinguish from which focal point they were emitted: Hg from the CAP, and Zn and
      Cr from the CF. The combined use of moss bags and geostatistical techniques
      allowed characterization of the emissions and identification of focal points of
      contamination in the study area.

PMID- 15261727
TI  - Highly toxic thallium in plants from the vicinity of Olkusz (Poland).
AB  - Thallium is a highly toxic metal that plays no role in the metabolism of plants
      or animals. Recent studies using small mammals and bird feathers as bioindicators
      demonstrated for the first time that animals from the vicinity of the Boleslaw
      metal works near Olkusz (southern Poland) had large amounts of thallium in their
      tissues. Because of concern over these reports, four plant species (Plantago
      lanceolata, Biscutella laevigata, Dianthus carthusianorum, Silene vulgaris)
      growing wildly in the same area on a 100-year-old calamine waste heap, as well as
      the waste heap soil, were examined. The average concentration of thallium in the
      waste heap soil was 43 mgTl/kg dry wt, with the highest value 78 mg Tl/kg dry wt.
      P. lanceolata accumulated extremely large amounts of thallium (average, 65 mg
      Tl/kg dry wt; maximum 321 mg Tl/kg dry wt in roots). S. vulgaris and D.
      carthusianorum accumulated much less (averages, 10 and 6.5 mg Tl/kg dry wt,
      respectively). On the other hand, B. leavigata accumulated negligible amounts of
      thallium in its tissues. The concentration of thallium in plants (shoots, roots)
      from the calamine waste heap was 100-1000 times the level normally found in
      plants (0.05 mg Tl/kg dry wt). Possible sources of thallium are discussed and the
      urgent need for large-scale studies on thallium contamination of soils and
      vegetation in Poland, especially its southern regions, which are the most
      industrialized, is pointed out.

PMID- 15261728
TI  - Modulation of flyash-induced genotoxicity in Vicia faba by vermicomposting.
AB  - Cytogenetic effects of pre- and postvermicomposted flyash samples were evaluated
      on the root meristem cells of Vicia faba. Seedlings of V. faba were directly sown
      in flyash and cow dung-soil mixtures (20%, 40%, 60%, and 80%) and the lateral
      roots grown in these test mixtures were sampled at 5 days. Negative control was
      run parallel in cow dung-soil (CS) mixture alone. One set of flyash-cow dung-soil
      (FCS) mixture was subjected to vermicomposting by introducing Eisenia foetida
      species of earthworms for 30 days and the cytogenetic effects were reinvestigated
      through V. faba root meristems. Chemical analysis carried out prior to
      vermicomposting revealed high concentrations of heavy metals such as Cr, Cu, Pb,
      Zn, and Ni in FCS samples. CS samples also showed the presence of these metals.
      Cytogenetic examinations of root meristems exposed to the FCS mixtures showed
      significant inhibition of mitotic index (MI), induction of chromosome aberrations
      (CA), and a significantly increased frequency of mitotic aberrations (MA). The
      increase of the aberrations was dependent on the flyash concentrations. Roots
      grown in CS samples also showed chromosomal and MAs; however, the percentage was
      lower than that observed with FCS and also statistically nonsignificant.
      Cytogenetic analysis of vermicomposted samples of FCS revealed a 15-45% decline
      in the aberration frequencies whereas chemical analysis showed a 10-50% decline
      in the metal concentrations, viz. Cr, Cu, Pb, Zn, and Ni, which indicates E.
      foetida a potential accumulator of heavy metals and the decline in metal
      concentrations may be the cause of the decrease in aberration frequencies. The
      present study indicates the genotoxicity potential of flyash and also the
      feasibility of vermicomposting for cleanup of metal-contaminated soil to mitigate
      the toxicity/genotoxicity.

PMID- 15261729
TI  - Metal content in femoral head spongious bone of people living in regions of
      different degrees of environmental pollution in Southern and Middle Poland.
AB  - The content of calcium, phosphorus, magnesium, potassium, iron, zinc, copper,
      lead, cadmium, arsenic, and silver was evaluated in femoral head spongious bone
      of inhabitants of southern (Silesia, n = 13; Cracow, n = 13) and middle Poland
      (Lodz, n = 12). A total of 38 persons (29 females and 9 males) were included in
      the study. The average age in the Silesian group was 68 +/- 9.9 years old, in the
      group from Cracow 69.2 +/- 9.6 years old, and 68.3 +/- 7.3 years old for the
      inhabitants of Lodz. The AAS method was used to determine the femoral heads metal
      content after microwave mineralization. A similar content of calcium (av 18.4%
      dry weight), phosphorus (av 6.8%), magnesium (av 1883.5 microg/g), potassium (av
      598.1 microg/g), iron (av 59.5 microg/g), zinc (av 90.1 microg/g), copper (av
      90.1 microg/g), arsenic (av 0.3 microg/g), and silver (av 0.03 microg/g) was
      found in every group. Specimens from different regions differed in lead and
      cadmium content, illustrating the differences in environmental pollution
      exposure.

PMID- 15261730
TI  - Acute and subchronic oral toxicity of fluoranthene in F-344 rats.
AB  - We have studied the acute and subchronic oral toxicity of fluoranthene (FLA) in
      male and female F-344 rats. Single acute FLA doses of 0, 1000, 2000, and 3000
      mg/kg body weight (BW) dissolved in peanut oil were administered daily by oral
      gavage. Subchronic doses of 0, 150, 750, and 1500 mg FLA/kg BW/day were
      administered for 90 days in the rats' diet. The toxicological endpoints examined
      included rat body and organ weights, as well as histopathological examinations of
      liver, kidney, stomach, prostate, testes, and ovaries; hematological parameters
      including red blood cell (RBC) counts, white blood cell (WBC) counts, hemoglobin
      (Hgb) concentration, hematocrit (Hct) concentration, mean corpuscular volume
      (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin
      concentration (MCHC); blood chemistry including alanine amino transferase (ALT),
      aspartate amino transferase (AST), blood urea nitrogen (BUN); and urine chemistry
      including glucose, bilirubin, specific gravity, pH, protein, urobilinogen,
      nitrite, occult blood, and leukocytes. In acute toxicity studies, WBC counts were
      significantly decreased and MCHC was significantly increased in both males and
      females at all doses. In the subchronic study, several of the blood cell
      parameters were significantly decreased in males and females after 90 days; RBCs
      (< or = 10877;12%), WBCs (< or = 10877;40%), Hct (< or = 10877;9%), and Hgb (< or
      = 10877;12%). Only BUN in males was significantly increased in the high-dose
      group (1500 mg FLA/kg BW/day) at the 90-day time point. None of the other
      clinical chemistry parameters were affected. The histopathological examinations
      showed significant abnormalities (tubular casts) only in the male kidney at the
      two highest doses after 90 days. We propose a subchronic oral no-observed-adverse
      effect level (NOAEL) of 150 mg/kg BW/day for FLA in rats, based on the
      hematological and renal changes. Overall, our findings indicate that FLA affects
      specific hematological parameters and kidneys, and has a greater effect on males
      than females.

PMID- 15261731
TI  - Dynamics of cytochrome P450 inducers in polluted sites of Sao Paulo city
      reservoirs.
AB  - The first analysis of water pollutants using biomarkers at the Guarapiranga
      Reservoir, which supplies water for one-third of the population of the Sao Paulo
      megalopolis (Brazil), is reported. Studies were performed before and after the
      start of water pumping to the Guarapiranga from the highly polluted Billings
      reservoir. Billings's water was purified by passing through the natural wetland
      located near Guarapiranga. Liver enzymes of Oreochromis niloticus (tilopias)
      obtained from both reservoirs served as biomarkers of pollution in a comparison
      with animals obtained from a reference site. Enhanced levels of total cytochromes
      P450 (3.4 times) and b5 (2.7 times) and activity of cytochrome c (P450) reductase
      (2.2 times) were observed in specimens collected near the water influx from the
      Billings before the pumping started. However, these parameters were significantly
      decreased 3 months later. This effect is probably due to dilution of pollutants
      because of the increased level of water in the Guarapiranga.

PMID- 15261732
TI  - A test battery for the ecotoxicological evaluation of the agri-chemical Environ.
AB  - The ecotoxicological effects of the agri-chemical Environ were evaluated using a
      test battery comprising organisms representing three trophic levels of the
      aquatic ecosystem. The sensitivities of the test species to Environ were as
      follows: Microtox > Daphnia magna > Pseudokirchneriella subcapitata =
      Thamnocephalus platyurus = Oncorhynchus mykiss > Artemia salina > Tetrahymena
      thermophilia. An order of magnitude sensitivity between the test species was
      observed which emphasizes the importance of a test battery approach in the
      assessment of possible ecological consequences of agri-chemicals. In addition,
      the aquatic bioassays were found to be more sensitive (e.g., greater than three
      orders of magnitude for D. magna) than previously reported mammalian toxicity
      data for Environ. Toxicity of Environ was also investigated using fish (RTG-2)
      and human fibroblast cell lines (HepG2 cells) and juvenile O. mykiss. Environ was
      shown to have greater toxicity in the acute lethality test than with the fish
      cell line. However, in vivo/in vitro comparisons in this instance we feel would
      be premature and imprecise owing to valid concerns regarding fish loading rates
      for the in vivo test, and exposure duration with the in vitro test.

PMID- 15261733
TI  - A comparative toxicologic and genotoxic study of the herbicide arsenal, its
      active ingredient imazapyr, and the surfactant nonylphenol ethoxylate.
AB  - The herbicide arsenal 250 NA, its technical-grade active ingredient imazapyr, and
      the surfactant nonylphenol ethoxylate (NP) were evaluated through genotoxicity
      and toxicity studies in different organisms. A comparative study of these three
      compounds was carried out to assess how the addition of surfactant components may
      pose the highest toxicological risk to pesticide formulations. The results showed
      that arsenal, imazapyr, and NP did not cause chromosome aberration in Allium cepa
      nor increase the frequency of micronuclei in mice. However, toxicological
      evaluations showed that NP was the most toxic compound to mice, A. cepa,
      Drosophila melanogaster, and Biomphalaria tenagophila. In this evaluation, it was
      observed that the adverse effects were produced by the surfactant additive of the
      pesticide formulation.

PMID- 15261734
TI  - Effect of fungicide iprodione on soil bacterial community.
AB  - The effect of the fungicide iprodione on soil bacterial communities was studied
      by treating two kinds of soils with different concentrations of iprodione.
      Degradation rates of iprodione in sterile and unsterile soils were also
      investigated. Residues of iprodione were measured by using high-performance
      liquid chromatography (HPLC) and a change of bacterial communities was performed
      with denaturing gradient gel electrophoresis (DGGE) by counting the 16S rDNA band
      on DGGE patterns. The degradation rate of iprodione was slower in sterile soil
      than in unsterile soil in both Da-Hu sandy loam and Kuan-Shi loam. After
      treatment with fungicide, soil bacterial communities were changed and recovered
      rapidly to the original status when incubated at a lower temperature (15 degrees
      C) and a lower iprodione concentration (5 microg/g). At the same temperature but
      with more iprodione (50 microg/g) added, the soil bacterial community increases
      slowly and regains the original status slowly. However, when incubated at the
      higher temperature (30 degrees C), the soil bacterial community is more complex
      than that at the lower temperature. The response of the soil bacterial community
      to the iprodione is faster at the higher than at the lower temperature. At 30
      degrees C and with 50 microg/g iprodione, the amounts of soil bacterial
      communities increased quickly but cannot be reduced to the original status after
      incubation for 23 days.

PMID- 15261735
TI  - Evidence for endocrine disruption in invertebrates.
AB  - The issue of endocrine disruption (ED) in invertebrates has generated remarkably
      little interest in the past compared to research with aquatic vertebrates in this
      area. However, with more than 95% of all known species in the animal kingdom,
      invertebrates constitute a very important part of the global biodiversity with
      key species for the structure and function of aquatic and terrestrial ecosystems.
      Despite the fact that ED in invertebrates has been investigated on a smaller
      scale than in vertebrates, invertebrates provide some of the best documented
      examples for deleterious effects in wildlife populations following an exposure to
      endocrine-active substances. The article provides an overview of the diversity in
      endocrine systems of invertebrates. The principal susceptibility of invertebrates
      to endocrine-active compounds is demonstrated with the case studies of
      tributyltin effects in mollusks and of insect growth regulators, the latter as
      purposely synthesized endocrine disrupters. The additional evidence for ED in
      invertebrates from laboratory and field studies is summarized as an update and
      amendment of the EDIETA report from 1998. Finally, conclusions about the scale
      and implications of the observed effects are drawn and research needs are
      defined.

PMID- 15261736
TI  - Biology of lysenin, a protein in the coelomic fluid of the earthworm Eisenia
      foetida.
AB  - Lysenin is a protein of 33?kDa in the coelomic fluid (CF) of the earthworm
      Eisenia foetida. It differs from other biologically active proteins, such as
      fetidins, eiseniapore, and coelomic cytolytic factor (CCF-1), that have been
      found in Eisenia foetida, in terms of both its biochemical and its biological
      characteristics. The large coelomocytes and free chloragocytes in the typhlosole
      of Eisenia foetida appear to be the cells that produce lysenin since the mRNA for
      lysenin and immunoreactive lysenin have been found in these cells. Lysenin binds
      specifically to sphingomyelin (SM) but not to other phospholipids in cell
      membranes. After binding to the cell membranes of target cells, lysenin forms
      oligomers in an SM-dependent manner, with subsequent formation of pores with a
      hydrodynamic diameter of approximately 3?nm. The biochemical interactions between
      lysenin and SM in cell membranes are responsible for the pharmacological
      activities of lysenin and of CF that contains lysenin in vertebrates, such as
      hemolysis, cytotoxicity, and contraction of smooth muscle in vitro and
      vasodepressor activity and lethality in vivo. When incubated with SM-liposomes,
      CF and lysenin lost some or all of their activity, an observation that suggests
      that SM might be involved in the induction of the various activities of lysenin
      and CF. However, in general, lysenin is neither cytotoxic nor lethal to
      invertebrates. An attempt has been made to explain the differences in the
      responses to lysenin and CF between vertebrates and invertebrates in terms of the
      presence or absence of SM in the various animals. Among Protostomia, SM is absent
      in Lophotrochozoa, with the exception of some molluscan species, but it is
      present in Ecdysozoa, with the exception of Nematomorpha and flies. Among
      Deuterostomia, Echinodermata and Hemichordata lack SM but SM is found in
      Chordata. Thus, the difference in terms of the response to lysenin between
      invertebrates and vertebrates cannot be fully explained by reference to the
      presence or absence of SM in the organism. Lysenin and its antiserum have made it
      possible to localize SM in the cell membranes. They should be a useful tool for
      studies of membrane physiology and the role of SM.

PMID- 15261737
TI  - Testican-1: a differentially expressed proteoglycan with protease inhibiting
      activities.
AB  - Testican-1 is a highly conserved, multidomain proteoglycan that is most
      prominently expressed in the thalamus of the brain, and is upregulated in
      activated astroglial cells of the cerebrum. Several functions of this gene
      product have now been demonstrated in vitro including membrane-type matrix
      metalloproteinase inhibition, cathepsin L inhibition, and low-affinity calcium
      binding. The purified gene product has been shown to inhibit cell attachment and
      neurite extensions in culture. Functions of testican in vivo have yet to be
      demonstrated in knockout mice or other models. Testican has been shown to carry
      substantial amounts of chondroitin sulfate as well as other oligosaccharides, but
      the biological significance of these embellishments is not yet known.

PMID- 15261738
TI  - Transgenic mice as an in vivo model of lymphomagenesis.
AB  - This review covers multiple data obtained on genetically modified mice that help
      to elucidate various intricate molecular mechanisms of lymphomagenesis in humans.
      We are in a "golden age" of mouse genetics. The mouse is by far the most
      accessible mammalian system physiologically similar to humans. Transgenic mouse
      models have illuminated how different genes contribute to human lymphomagenesis.
      Multiple experiments with transgenic mice have not only confirmed the data
      obtained for human lymphomas but also gave additional evidence for the role of
      some genes and cooperative participation of their products in the development of
      human lymphomas. Genes and gene networks detected on transgenic mice can
      successfully serve as molecular targets for tumor therapy. This review
      demonstrates the extraordinary possibilities of transgenic technology, which is
      presently one of the readily available, efficient, and accurate tools to solve
      the problem of cancer.

PMID- 15261739
TI  - Bacterial endocytobionts of ciliophora and their interactions with the host cell.
AB  - Ciliates may be hosts for numerous bacteria, which can occupy almost all cellular
      compartments of the protists. About 200 ciliate species are recorded as hosts of
      different intracellular bacteria, being a small part of the diversity for such
      types of endocytobiosis in nature. In the Paramecium genus alone close to 60
      types of bacteria adapted for intracellular life are known. In this review
      extensive material concerning the variety of endocytobionts, their categories,
      and their interaction with host cells is presented. Special attention is paid to
      endocytobiosis in Paramecium with highly infectious bacteria Holospora, bacteria
      of the Caedibacter and Polynucleobacter genera, methanogenic bacteria, and
      "xenosomes" as well as to life cycles and strategies of bacterial
      endonucleobionts. The above model bacteria and their interactions with hosts have
      not been exhaustively studied. A number of unsolved problems concerning their
      interactions within an endocytobiotic system and their ecological implications
      remain to be studied.

PMID- 15261740
TI  - Basic helix-loop-helix proteins expressed during early embryonic organogenesis.
AB  - The basic helix-loop-helix proteins form a special group of transcription factors
      unique for the eukaryotic organisms. They are crucial for the embryonic
      development of many fundamental organ systems such as muscle, heart, central
      nervous system, hematopoiteic system, and many others. They are very flexible in
      terms of regulating transcription in that they can either promote or repress
      transcription, and do so in many different ways. Basic helix-loop-helix proteins
      can form homo- or heterodimers with other members of the group, and are subject
      to post-transcriptional modifications. In this review, an overview of basic helix
      loop-helix protein classification, biochemical function, and examples of past and
      recent advances in our understanding of embryonic development are presented, with
      emphasis on the vertebrate muscle, heart, brain, and eye.

PMID- 15261741
TI  - Testicular interstitial cells, and steroidogenic detection in the protogynous
      fish, Synbranchus marmoratus (Teleostei, Synbranchidae).
AB  - The swamp eel, Synbranchus marmoratus, is a freshwater protogynic diandric
      species. Primary males develop directly as males while secondary males arise from
      the sex reversal of females. Fishes from Argentine and Brazil inland waters were
      collected, examined and compared for this study. In order to characterize the
      interstitial testicular compartment, light and electron microscopy techniques and
      an enzyme histochemical examination for steroidogenic cells detection were used.
      The interstitial compartment of S. marmoratus is composed of Leydig and myoid
      cells, collagen fibers, blood cells, macrophages,and amyelinic nerves. At the
      ultrastructural level, no differences were observed in the interstitial tissue,
      either between specimens from the different sampling sites or between primary and
      secondary males. Leydig cells are present in all testes examined throughout the
      year. A cytoplasmatic reaction of 3beta-HSD was detected only in Leydig cells
      during sex reversal and in both type of males, mainly during the regressed and
      early maturation classes (autumn and winter). Leydig cells possess the typical
      fine structural characteristics associated with steroidogenesis. Furthermore, in
      both type of males, during sex reversal and after the spawning period, the number
      of granulocytes and macrophages present in the testes increased, suggesting that
      they could be involved in phagocytosis and resorption of damaged cells.

PMID- 15261742
TI  - Sperm structure and spermiogenesis in Coletinia sp. (Nicoletiidae, Zygentoma,
      Insecta) with a comparative analysis of sperm structure in Zygentoma.
AB  - The spermatozoon of Coletinia sp. has a bilayered acrosome, a short nucleus (4
      microm) and a relatively short sperm tail with two mitochondrial derivatives. The
      chromatin is uniformly dense except for several electron-lucid channels or
      strands which permeate the nucleus and which originate in the spermatid as
      invaginations of the nuclear envelope. The invaginations occur mostly or
      exclusively along two meridians of the spermatid that are also characterized by
      the presence of a longitudinal rod of medium electron density. The two rods
      (designated as 'mid-spermatid rods') evidently are instrumental in the formation
      of the electron-lucid channels. The significance of this elaborate system of
      intranuclear channels is not understood. The sperm tail has a 9 + 9 + 2 axoneme
      with each of the nine microtubular doublets accompanied by an accessory
      microtubule; scant intertubular material can also be distinguished. Hence, the
      tail axoneme resembles that of many pterygote insects. Each of the two
      mitochondrial derivatives contains a crystalline inclusion that has periodically
      spaced layers going in different directions on either side of the midline. Two
      synapomorphic traits appear to be shared by Ateluridae and Nicoletiidae, namely
      the invaginations of the nuclear membrane along two meridians of the nucleus and
      the shape of the crystalline inclusions of the mitochondrial derivatives. Four
      species from the family Lepismatidae were also examined as to their sperm
      ultrastructure. Three of them, Allacrotelsa kraepelini, Ctenolepisma longicaudata
      and Ctenolepisma sp., were found to be very similar to the two previously
      examined lepismatids, Thermobia domestica and Lepisma saccharina. On the other
      hand, spermatozoa of Tricholepisma aurea were aggregated in small groups rather
      than pairwise joined as seen in the other lepismatids. Sperm characters are also
      used to reconstruct a phylogenetic hypothesis which suggests a close relationship
      between Ateluridae and Nicoletiidae.

PMID- 15261743
TI  - About the T-system in the myofibril-free sarcoplasm of the frog muscle fibre.
AB  - Previous investigations of the T-system in skeletal muscle fibres described the
      inter-myofibrillar relationships between T-tubules and the sarcoplasmic
      reticulum. They disregarded the arrangement of the T-system in the myofibril-free
      sarcoplasm in the area of muscle fibre nuclei. In the present investigation, the
      T-system was filled by means of lanthanum incubation and the myofibril-free
      sarcoplasm was ultrastructural examined by means of thin (< or = 100 nm) as well
      as thick sections (> 300 nm-1 microm) with the electron microscope. The
      investigation of thick sections revealed that T-tubules meander through this
      myofibril-free sarcoplasm and tangle up at the poles of muscle fibre nuclei and
      in the area of fundamental nuclei of the motor end plate. They are, far from
      myofibrils, in proximity to these nuclei, the Golgi apparatus and mitochondria.
      On basis of this proximity and their openings at the muscle fibre surface, a
      contribution at the drainage of metabolic products and at the local calcium
      control is discussed.

PMID- 15261744
TI  - About the morphological relationships of the sarcoplasmic reticulum in the sole
      plate area of the frog.
AB  - In the present investigation the sole plate area of motor end plates of the frog
      is ultrastructurally examined with different postfixation methods. We
      concentrated in this case on the proof of the smooth and rough sarcoplasmic
      reticulum of the sole plate. The relations of the smooth and rough sarcoplasmic
      reticulum to subsynaptic folds and the local T-system and its connections to
      diads and triads in the sole plate area are represented. The morphological
      differences between mammal and frog are pointed out. The possible functions of
      the sarcoplasmic reticulum in the myofibril-free sarcoplasm are discussed.

PMID- 15261745
TI  - snRNPs are present in the karyosome capsule in the weevil germinal vesicle.
AB  - Within the oocyte nucleus of the apple blossom weevil, Anthonomus pomorum
      (Insecta, Coleoptera) highly condensed and transcriptionaly inactive chromosomes
      form the karyosome. During its formation, within the nucleoplasm numerous,
      variably sized spherical inclusions termed nuclear bodies occur. As oogenesis
      progresses, the karyosome is gradually surrounded by a prominent sheath, the
      karyosome capsule. The function and molecular composition of both the nuclear
      bodies and the karyosome capsule are largely unknown. Using cytochemical methods
      we demonstrate that DNA is confined to the karyosome and there is no
      extrachromosomal DNA accumulations within the nucleoplasm. In addition, none of
      the oocyte nucleus subdomains contain argyrophilic proteins. Our immunoEM study
      revealed that in contrast to similar structures in germinal vesicles in other
      insect species, the nuclear bodies of A. pomorum do not cross-react with
      antibodies recognising small nuclear ribonucleoproteins, coilin or the splicing
      factor SC-35. Unexpectedly, we found that as the karyosome capsule develops,
      mature small nuclear RNAs and proteins containing the Sm epitope associate with
      the capsule material. We suggest that the karyosome capsule is a storage site for
      small nuclear ribonucleoprotein particles, which may be used during early
      embryonic development.

PMID- 15261746
TI  - Ultrastructure of early jurassic fossil plant cuticles: Pachypteris gradinarui
      Popa.
AB  - Exceptional preservation of extinct Pachypteris extra-epidermal cuticle enabled
      the first detailed statistical measurements of its ultrastructure using
      transmission electron microscopy. Pachypteris is a leaf genus of the Mesozoic
      belonging to seed fern foliage of the order Corystospermales. The species studied
      in this paper is Pachypteris gradinarui Popa [Rev. Palaeobot. Palynol. 111 (2000)
      31], based on fossils which are Early Jurassic in age (Hettangian-Sinemurian,
      approximately 205-190 million years old). Both the upper and the lower cuticles
      were thoroughly examined, including the detail of the stomatal complexes and
      epidermal cells. The data obtained from our TEM analysis, together with the
      confidence intervals, were very useful to give precise description of the
      cuticles as they distinguished between upper and lower epidermal and stomatal
      cell types. Moreover a combination of characters was used to develop the first
      dichotomous key based on ultrastructural characters, i.e. not only the total
      thickness of the cuticle but also details and proportions of A cuticle proper and
      B cuticular layer. Comparisons with ultrastructures known from other Pachypteris
      species show that the influence of space and time, diagenetic processes, and/or
      processes related to technical procedures, seem to be minimal within this genus.
      Detailed studies of this type may be very useful for further comparisons among
      other species and at higher taxonomical ranks.

PMID- 15261747
TI  - A contribution to the functional morphology of the midgut gland in phalangiid
      harvestmen Gyas annulatus and Gyas titanus during their life cycle.
AB  - The structure of the midgut gland and its changes in different seasons have been
      examined in the harvestmen Gyas annulatus and Gyas titanus (Arachnida: Opiliones:
      Phalangiidae). In both species, in the epithelium of the midgut gland two
      different types of cells are present: secretory and digestive ones. The secretory
      cells are characterized by plentiful rER and secretory granula. The digestive
      cells are characterized by an apical system of tubules. Both cells are connected
      by prominent specialized junctions. If a secretory cell is in contact with a
      digestive cell, rER cisterna are in close vicinity and parallel to these
      junctions. As found light- and electron microscopically and also histochemically,
      glycogen and lipids are stored in both cells. In both species, glycogen was seen
      to be used as energy compound during overwintering. At the end of their life, the
      digestive cells develop into excretory ones, containing metabolic wastes.

PMID- 15261748
TI  - The presence of a galanin-like peptide in the gut neuroendocrine system of
      Lampetra fluviatilis and Acipenser transmontanus: an immunohistochemical study.
AB  - Galanin is a brain-gut neuropeptide present in the central and peripheral nervous
      systems of vertebrates. In the present survey, the galaninergic and the diffuse
      endocrine systems of the alimentary canal of the river lamprey, Lampetra
      fluviatilis, and the white sturgeon, Acipenser transmontanus, were studied by
      immunohistochemistry. The results show the presence of galanin-like
      immunoreactive endocrine cells in the gut of L. fluviatilis. In addition, a
      galanin-like immunoreactivity was detected in enteric intramural neurons of both
      species. It is conceivable that the galaninergic system plays in both species a
      role in the regulation of the gut muscle contractility and in the modulation of
      mucosal secretive/absorptive processes. In A. transmontanus, the presence of
      galanin-like immunoreactive nerve fibres associated with components of the gut
      associated-lymphoid tissue is possibly correlated with a control of the defensive
      events at this site. The presence of a galanin-like immunoreactivity in the
      neuroendocrine system of these two ancient fishes confirms the hypothesis on the
      early occurrence of this regulative molecule in the gastro-enteric system of
      vertebrates.

PMID- 15261749
TI  - Ultrasound instrumentation.
AB  - Ultrasound is used in all areas of general surgery and many surgical
      subspecialties. The surgeon with ultrasound skills brings a number of advantages
      to clinical practice, including the ability to view dynamic images that are far
      superior to the interpretation of static ultrasound images. However, to obtain
      optimal ultrasound images, the surgeon sonographer must know the equipment well.
      This article provides an overview of the various types of ultrasound
      instrumentation, their settings, their care, and their uses ina variety of
      clinical situations.

PMID- 15261750
TI  - Ultrasound in head and neck surgery: thyroid, parathyroid, and cervical lymph
      nodes.
AB  - Ultrasound (US) of the neck is extremely sensitive in detecting thyroid,
      parathyroid, and cervical lymph node pathology, and is regarded as the most
      complete and cost-effective imaging method for evaluating the thyroid and
      parathyroid glands, as well as for the diagnostic evaluation of the cervical
      lymph node basin. US is widely used in screening high-risk individuals,
      evaluation of palpable and nonpalpable thyroid nodules, needle guidance for
      biopsy of nonpalpable and suspicious nodules, and preoperative evaluation of the
      extent of thyroid neoplasms, as well as in the detection of residual, recurrent,
      or metastatic thyroid tumors, and in observing nonsurgical cases. It has thus
      become an important adjunct to the practice of head and neck surgery.

PMID- 15261751
TI  - Updates in breast ultrasound.
AB  - Ultrasound is becoming an indispensable tool for the surgeon in the diagnosis and
      treatment of a variety of breast problems. Hands-on ultrasound education for
      surgeons and the ongoing improvements in imaging technology have made surgeon
      performed breast ultrasound an effective method of identifying and diagnosing
      breast lesions and have increased the surgeon's ability to perform ultrasound
      guided interventional procedures. This article reviews the current state of
      surgeon-performed breast ultrasound.

PMID- 15261752
TI  - Endoscopic ultrasonography.
AB  - Endoscopic ultrasound (EUS) was introduced in the early 1980s in an attempt to
      improve sonographic imaging of the pancreas. Its uses have been expanded to
      include examination of the upper and lower gastrointestinal tracts, hepatobiliary
      and portal systems,and the anal sphincter; diagnosis and staging of esophageal,
      gastric,and pancreaticobiliary tumors; and evaluation of mediastinal nodes in
      lung cancer. Although EUS has its limitations and is greatly dependent on
      operator skill, it has wide-ranging interventional and therapeutic applications
      that can be expected to increase in the future with technologic advances and
      greater educational opportunities for physicians.

PMID- 15261753
TI  - Laparoscopic ultrasound.
AB  - Laparoscopic ultrasonography is a relative latecomer to the area of surgical
      sonography whose arrival can be attributed to the need for development of
      specialized transducers that could fit through conventional laparoscopic trocars.
      The quality, reliability, and ease of use of such units has evolved rapidly, so
      that laparoscopic ultrasonography may now be performed on a routine basis.
      Laparoscopic ultrasonography allows the surgeon to look into the tissues being
      operated upon, thereby compensating for the inability to physically palpate such
      tissues. Thus, it has not only helped to mimic open surgery, but has also refined
      the current techniques of laparoscopic operations. With the increasing
      availability of equipment, as well as the training of surgeons in this modality,
      laparoscopic ultrasound is quickly becoming an essential tool for the surgeon
      aiming to take laparoscopic surgery to new frontiers.

PMID- 15261754
TI  - Intraoperative ultrasound.
AB  - Intraoperative ultrasound (IOUS) can provide various diagnostic information that
      is otherwise not available, and can guide or assist various surgical procedures
      in real time. With refinement of equipment, IOUS is currently used in a wide
      variety of surgical operations,such as hepatobiliary, pancreatic, endocrine,
      cardiovascular,and neurologic surgery. Our overview of IOUS, including
      instrumentation,techniques, indications, advantages, disadvantages,and future
      perspective, is described in this article. Being safe, quick, accurate, and
      versatile intraoperatively, IOUS is a valuable technique that surgeons are
      recommended to master to improve intraoperative decision making and surgical
      procedures.

PMID- 15261755
TI  - What's new in vascular ultrasound.
AB  - Duplex ultrasound has long been the method of choice in the diagnosis and
      evaluation of deep venous thrombosis and carotid artery stenosis and in
      monitoring lower extremity bypasses. In recent years, innovative procedures and
      technology have fostered new applications for duplex ultrasound, such as
      detection of in-stent stenosis and endoleaks, intraoperative evaluation of in
      situ vein bypasses and monitoring of endovenous procedures, and treatment of
      common femoral pseudoaneurysms. The low cost and noninvasiveness of duplex
      ultrasound make it ideal for such studies,as well as for screening for
      asymptomatic vascular disease.

PMID- 15261756
TI  - Surgeon-performed ultrasound: endorectal ultrasound.
AB  - Endorectal (ERUS) and endoanal (EAUS) ultrasound imaging is increasingly being
      performed by surgeons in the office and outpatient setting for the assessment of
      both benign and malignant disease. Multiple studies have demonstrated the
      accuracy of these modalities in identifying pertinent anatomy and anatomic
      abnormalities. The ultrasound is easily tolerated by most patients, and is easily
      performed with minimal preparation on the patient's part. The ability of the
      surgeon to perform and interpret this straight forward diagnostic procedure
      allows for the simplification of the diagnostic process and a more rapid
      determination of treatment options for the patient.

PMID- 15261757
TI  - Surgeon-performed ultrasound in the ICU setting.
AB  - Evaluation of critically ill patients is often challenging due to altered
      sensorium, underlying disease, and the presence of multiple drains or monitoring
      devices. In such circumstances, the ability of physicians to perform ultrasound
      examinations in the intensive care unit provides a useful diagnostic and
      therapeutic adjunct. In this article,we review the application of surgeon
      performed ultrasonography in the evaluation and management of critically ill
      patients.

PMID- 15261759
TI  - The cytoprotective effect of inulin-type hexasaccharide extracted from Morinda
      officinalis on PC12 cells against the lesion induced by corticosterone.
AB  - High concentration of corticosterone (Cort) 0.2 mM was incubated with PC12 cells
      to simulate the lesion state of brain neurons in depressive illness, it was found
      that the inulin-type oligosaccharides extracted from Morinda officinalis, inulin
      type hexasaccharide (IHS) at the doses of 0.625, 1.25 microM or desipramine (DIM)
      0.25, 1 microM protected the PC12 cells from the lesion induced by Cort. With
      Fura-2/AM labeling assay, DIM 0.25, 1 microM or IHS 2.5, 10 microM attenuated the
      intracellular Ca2+ overloading induced by Cort 0.1 mM for 48 h in PC12 cells.
      Using RT-PCR, treatment with Cort 0.1 mM for 48 h decreased the nerve growth
      factor (NGF) mRNA level in PC12 cells, IHS 5, 10 microM reversed this change. In
      summary, IHS attenuate the intracellular Ca2+ overloading and thereby up-regulate
      the NGF mRNA expression in Cort-treated PC12 cells, which may be consisted at
      least part of the cytopretective effect of IHS. These results also extend
      evidence for our hypothesis that neuroprotective action is one of the common
      mechanisms for antidepressants.

PMID- 15261760
TI  - Molecular process in acute liver injury and regeneration induced by carbon
      tetrachloride.
AB  - Injection of carbon tetrachloride (CCl4) intraperitoneally into model animals
      induces acute liver injury mediated by reactive oxygen species (ROS) as normal
      metabolites in hepatocytes. In this study, the molecular process in this type of
      liver injury was analyzed from the aspect of liver function and regulatory
      factors. Down-regulation of liver-specific genes was accomplished through
      suppression of liver-enriched transcription factors and box A factors found in
      the catalase gene, and induction of NF-kappaB, AP-1 and a novel factor denoted as
      'cx' in the catalase gene. Expression profiles of these genes were restored to
      normal levels in the late stage of injury (48 h). On the other hand, hepatocyte
      growth factor (HGF) and proliferating cell nuclear antigen (PCNA) were induced in
      the early stage (6 h) and 36 h, respectively. Interestingly, ERK2 was transiently
      activated at 3 h CCl4-treatment. These observations suggested that hepatotoxin by
      CCl4-injection concomitantly induces both processes in acute injury and liver
      regeneration.

PMID- 15261761
TI  - Age-related changes of antioxidant enzyme activities, glutathione status and
      lipid peroxidation in rat erythrocytes after heat stress.
AB  - The aim of this study was to determine whether exposure to heat stress would lead
      to oxidative stress and whether this effect varied with different exposure
      periods. We kept 1-, 6- and 12-month-old male Wistar rats at an ambient
      temperature of either 22 degrees C or 40 degrees C for 3 and 7 days and measured
      glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn
      SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px) and
      glutathione-S-transferase (GST) activities and levels of thiobarbituric acid
      reactive substances (TBARS), reduced glutathione (GSH) and oxidized glutathione
      (GSSG) in erythrocytes and determined GSH/GSSG ratio, total glutathione and the
      redox index. G-6-PD and CAT activities were found to be significantly increased
      in 1- and 6-month-old rats after 3 and 7 days of heat stress, but G-6-PD
      activities decreased in 12-month-old rats. Cu, Zn-SOD activity decreased in 1
      month-old rats after heat stress, whereas it increased in 6- and 12-month-old
      rats. GST activity increased in all groups. GSH and total GSH levels and GSH/GSSG
      ratios decreased in 1- and 6-month-old rats but they increased in 12-month-old
      rats after heat stress. GSSG levels increased in 1- and 6-month-old rats but
      decreased in 12-month-old rats after heat stress. TBARS levels increased in all
      groups. Seven days of stress is more effective in altering enzyme activities and
      levels of GSH, GSSG and TBARS. When the effects of both heat stress and aging
      were examined together, it was interesting to note that they mostly influenced G
      6-PD activity.

PMID- 15261762
TI  - 27-Hydroxycholesterol inhibits neutral sphingomyelinase in cultured human
      endothelial cells.
AB  - To study the effect of 27-hydroxycholesterol (27OHC) on the catabolism of
      sphingomyelin, we cultured endothelial cells (ECs) from human umbilical veins
      with 27OHC, then measured activities of acid sphingomyelinase (ASMase) and
      neutral sphingomyelinase (NSMase) and sphingomyelin consumption by using
      [14C]sphingomyelin, and determined NSMase mRNA expressions by RT-PCR method. The
      results indicated that [14C]sphingomyelin accumulated in cells treated with
      27OHC, and that the activities of both NSMase and ASMase were inhibited in ECs
      cultured with 27OHC. To further study the effect of 27OHC on NSMase, we used
      desipramine, an inhibitor of ASMase, to exclude the possible interference of
      ASMase's residual activity at neutral condition. Also, we observed the
      significant inhibition of NSMase activity by using glutathione, an inhibitor of
      NSMase, but found no further impact when 27OHC was added later. To determine
      whether the inhibition of NSMase activity was directly due to the effect of
      27OHC, we exposed cell homogenate to 27OHC, and found no inhibitive effect of
      27OHC on the activity of NSMase. All of our data confirmed that 27OHC had only an
      indirect inhibitive effect on NSMase. Our finding that no change of the NSMase
      mRNA expression by 27OHC indicated that the inhibitive effect of 27OHC on NSMase
      activity occurred at a post-transcriptional level. We suggest that an altered
      membrane fluidity caused by 27OHC could be involved in the inhibited activity of
      NSMase.

PMID- 15261763
TI  - Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells
      via inducing cell cycle arrest and apoptosis.
AB  - Angelica sinensis (Oliv.) Diels, a traditional Chinese medicine, has been widely
      prescribed in treatment of gynecological diseases. Bio-based assays for extracts
      of Angelica sinensis showed that the acetone extract (AE-AS) had dose-dependently
      antiproliferative effect on A549, HT29, DBTRG-05MG and J5 human cancer cells. The
      IC50 values of AE-AS on mentioned cancer cells ranged from 35 to 50 microg/ml
      after 24 h of treatment. After 72 h of exposure, AE-AS (40 microg/ml)
      significantly reduced A549 cell proliferation to 24 +/- 3.2% of control. In A549
      cells, the cell cycle analysis showed that AE-AS induced a significant increase
      in the number of cells in G0/G1, with a concomitant decrease in the number of
      cells in S phase. AE-AS-induced chromatin changes and apoptosis of A549 cells
      were confirmed by Hoechst 33342 DNA staining and annexin V staining. A549 cells
      treated with AE-AS caused activation of caspase-9 and -3, and AE-AS-induced
      apoptosis could be inhibited by the broad-spectrum caspase inhibitor, z-VAD-fmk.
      The Western blot indicated the AE-AS-triggered apoptosis is mediated via
      suppression of Bcl-2 oncoprotein expression rather than p53 or Bax. Besides, AE
      AS decreased the levels of cdk4 protein was observed. These results indicate that
      the AE-AS could induce G1/S arrest and activate the mechanism of apoptosis in
      human cancer cells. Extracts obtained from different methods of fractionation
      might possess distinct bioactivity. These results prompted us to further evaluate
      the in vivo anticancer effects and elucidate the chemical composition profile of
      AE-AS.

PMID- 15261764
TI  - Effect of chronic stress on the cardiac baroreflex in the post-weanling rat.
AB  - There is increasing evidence that early life stressors may program blood pressure
      control mechanisms such that the risk for cardiovascular disease in later life is
      increased. In the present investigation, the effect of repeated restraint/heat
      stress during the two-week period immediately after weaning on baroreflex
      function was determined and the contribution of brain angiotensin II (ANG II) to
      the changes was assessed in young, conscious, freely moving Sprague Dawley rats.
      In rats two weeks post weaning, basal MAP was significantly higher and basal HR
      significantly lower than rats tested immediately after weaning. This change in
      the operating point of HR was not accompanied by any changes in baroreflex
      function. Treatment with chronic icv infusion of losartan, an AT1 receptor
      antagonist, during the two-week period prevented the changes in basal MAP and HR.
      Chronic stress during the two weeks post weaning, whether due to surgical
      implantation of icv cannulae or due to restraint/heat stress, significantly
      shifted the set-point of the baroreflex function to a higher pressure. Chronic
      icv infusion of losartan during the period prevented these effects (at least in
      the case of stress due to the presence of icv cannulae) suggesting a role for
      brain ANG II in the change. Changes in the expression of CRH mRNA in the
      paraventricular nucleus could not explain the stress-related change in baroreflex
      function. If the rightward shift in the baroreflex persists into adulthood, it
      could increase the susceptibility to cardiovascular diseases such as
      hypertension.

PMID- 15261765
TI  - Release of choline in the isolated heart, an indicator of ischemic phospholipid
      degradation and its protection by ischemic preconditioning: no evidence for a
      role of phospholipase D.
AB  - The release of choline as a water-soluble product of phospholipid hydrolysis was
      measured in the perfusate of rat hearts to monitor ischemic membrane degradation
      and its protection by ischemic preconditioning (IPC). Hearts were subjected to
      global ischemia (GI; 30 min of no-flow) followed by 60 min of reperfusion. To
      induce IPC, GI was preceded by four no-flow episodes of 5 min each. Deleterious
      consequences of GI and reperfusion, namely coronary flow reduction, incidence of
      arrhythmias and release of cardiac troponin T, were significantly attenuated by
      IPC. The release of choline increased during reperfusion in a biphasic manner: a
      first phase peaked immediately after GI and was followed by a second, delayed
      phase indicating choline release caused during reperfusion. Only the second phase
      was blocked by both IPC and by AACOCF3 (5 microM), an inhibitor of cytosolic
      phospholipase A2. The activity of phospholipase D (PLD) was unchanged after GI or
      IPC or GI plus IPC. In conclusion, choline release into heart perfusate was found
      to be a useful real-time indicator of phospholipid degradation caused by GI and
      by reperfusion and its protection by IPC. The results supplement previous
      observations on the accumulation of fatty acids in the phospholipid pool. There
      was no evidence for PLD activation by GI or IPC.

PMID- 15261767
TI  - Cytotoxic effects of mammea type coumarins from Calophyllum brasiliense.
AB  - Calophyllum brasiliense (Clusiaceae) is a big tree from the Tropical Rain Forests
      of the American continent. The organic extracts from the leaves yielded coumarins
      of the mammea type: mammea A/BA, A/BB, B/BA, B/BB, C/OA, C/OB, B/BA cyclo F, B/BB
      cyclo F, and isomammeigin. The triterpenoids friedelin and canophyllol, as well
      as the biflavonoid amentoflavone, protocatechuic and shikimic acids, were also
      obtained. Most of the isolated compounds were tested in vitro against K562, U251,
      and PC3 human tumor cell lines. The coumarins were cytotoxic against the three
      cell lines, the highest activity was shown by mammea A/BA (IC50 = 0.04 to 0.59
      microM). The mixtures of mammea A/BA + A/BB, mammea B/BA + B/BB and mammea C/OA +
      C/OB were also highly active (IC50 < 4.05 microM). Friedelin was cytotoxic only
      against PC3, and U251 lines. Inhibition of HIV-1 reverse transcriptase was also
      assayed in vitro; however, none of the tested compounds (250 microM) prevented
      the activity of this enzyme. Most of the isolated compounds were also inactive
      against fourteen bacterial strains; however mammea A/BA + A/BB, and mammea C/OA +
      C/OB inhibited the growth of Staphylococcus aureus, S. epidermidis and Bacillus
      subtilis.

PMID- 15261766
TI  - Protective effect of ginseng extract against apoptotic cell death induced by
      2,2',5,5'-tetrachlorobiphenyl in neuronal SK-N-MC cells.
AB  - Oxidative stress plays an important role in the pathological processes of
      neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous
      environmental contaminants, some of which may be neurotoxic. 2,2',5,5'
      Tetrachlorobiphenyl (PCB 52) induces apoptotic death in human neuronal SK-N-MC
      cells, as demonstrated by gel electrophoresis, which demonstrates the proteolytic
      cleavage of beta-catenin and poly(ADP-ribose) polymerase (PARP) and the
      characteristic ladder patterns of DNA fragmentation. In the present study, we
      investigated whether Panax ginseng extract protect human neuronal SK-N-MC cells
      from PCB 52-induced apoptosis. The addition of 500 microg/ml of ginseng extract
      to a culture medium significantly protected neuronal cell from the apoptosis
      mediated by PCB 52 and remarkably attenuated lipid peroxidation, the generation
      of reactive oxygen species, and DNA fragmentation, and markedly reduced the PCB
      52 induced proteolytic cleavage of beta-catenin and PARP. These results show that
      Panax ginseng extract protects human neuronal SK-N-MC cells from the apoptosis
      induced by PCB 52. We suggest that Panax ginseng extracts may protect neuronal
      cells from oxidative injury.

PMID- 15261768
TI  - Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived
      apoptosis: the role of the MAPK family.
AB  - Gastrodia elata (G. elata) is a traditional Chinese herbal medicine for treating
      headaches, dizziness, tetanus, and epilepsy. In this study, differential methanol
      (MeOH) extracts of G. elata were found to prevent serum-deprived rat
      pheochromocytoma (PC12) cell apoptosis by the MTT assay and Hoechst staining. A
      serine/threonine kinase inhibitor attenuated this protection. G. elata resulted
      in phosphorylation and dephosphorylation of ERK1/2 and JNK1/2-p38 MAPKs (members
      of the serine/threonine kinase family), respectively, as revealed by Western blot
      analysis. An upstream ERK inhibitor attenuated G. elata-induced ERK
      phosphorylation but not protective effect. Although JNK and p38 inhibitors
      attenuated their related enzyme activities during serum deprivation, only JNK
      inhibitor prevented serum-deprived apoptosis. Thus, G. elata prevents serum
      deprived apoptosis through activation of the serine/threonine kinase-dependent
      pathway and suppression of JNK activity.

PMID- 15261769
TI  - An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits hemocytic
      phospholipase A2 (PLA2) in tobacco hornworms Manduca sexta.
AB  - The entomopathogenic bacterium, Xenorhabdus nematophila, induces immunodepression
      in target insects and finally leads to lethal septicemia of the infected hosts. A
      hypothesis has been raised that the bacteria inhibit eicosanoid-biosynthesis
      pathway to interrupt immune signaling of the infected hosts. Here, we show direct
      evidence that X. nematophila inhibits the activity of phospholipase A2 (PLA2),
      the initial step in the eicosanoid-biosynthesis pathway. Inhibition of PLA2 was
      dependent on both incubation time with X. nematophila and the bacterial
      concentration in in vitro PLA2 preparations of Manduca sexta hemocytes. While
      living bacteria inhibited PLA2 activity, heat-killed X. nematophila rather
      increased PLA2 activity. X. nematophila secreted PLA2 inhibitor(s) which were
      detected in the organic, but not aqueous, extract of the bacterial culture
      medium. The PLA2 inhibitory activity of the organic extract was lost after heat
      treatment. These results clearly indicate that X. nematophila inhibits PLA2
      activity, and thereby inhibits eicosanoid biosynthesis which leads to
      immunodepression of the infected hosts.

PMID- 15261770
TI  - Quantification and kinetics of the decline in grass grub endopeptidase activity
      during initiation of amber disease.
AB  - Amber disease in the grass grub (Costelytra zealandica White) (Coleoptera:
      Scarabaeidae), caused by strains of the bacteria Serratia entomophila or S.
      proteamaculans, is characterised by cessation of feeding and clearance of the
      midgut. Analysis of the midgut enzyme activity in diseased grass grub larvae
      showed that proteolytic activity was reduced to low levels. The endopeptidases,
      trypsin, elastase, and chymotrypsin, were all markedly reduced in activity
      whereas the exopeptidases (leucine-aminopeptidase and carboxypeptidase A and B)
      were much less affected. There was no effect on the non-proteolytic enzymes,
      esterase and alpha-amylase. Sequential analysis of enzyme levels in the gut
      during onset of disease showed that proteolytic activity dropped after cessation
      of feeding and preceded gut clearance. In starved, uninfected larvae enzyme
      activity levels remained high, indicating that decline in enzyme activity is not
      associated with absence of food and cessation of feeding, but with the onset of
      disease.

PMID- 15261771
TI  - Histology, ultrastructure, and morphogenesis of a rickettsia-like organism
      causing disease in the oyster, Crassostrea ariakensis Gould.
AB  - Moribund specimens of the oyster, Crassostrea ariakensis Gould, aged 2-3 years
      were collected from Hailing Bay in Yangxi County of Guangdong Province from
      February to May and November to December in the years 2001, 2002, and 2003. A
      massive infection by an obligate intracellular prokaryote, specifically a
      rickettsia-like organism (RLO), was found. Here we report investigations of this
      RLO in the tissues of the oyster C. ariakensis Gould and describe the histology,
      ultrastructure, and morphogenesis of this pathogen in C. ariakensis Gould. Light
      microscopic observations of stained tissues revealed cytoplasmic inclusion bodies
      typical of prokaryote infection in about 87% (26/30) of the oysters. Most
      inclusions were observed in epithelial cells and connective tissues of the gill,
      mantle, and digestive gland of most of the infected oysters. The shape, size, and
      color of inclusions from different tissues were polymorphic. Electron microscopic
      examination of digestive gland, gill, and mantle tissues showed that the RLOs
      were intracytoplasmic. RLOs were often round, dumb-bell-shaped (undergoing binary
      fission), or occasionally rod-shaped and ranged from approximately 0.58 to
      1.20microm in size. The organisms exhibited an ultrastructure characteristic of
      prokaryotic bacteria-like cells, including a trilaminar cell wall, electron-dense
      periplasmic ribosome zone, and a DNA nucleoid. Reproductive stages, including
      transverse binary fission, were observed by TEM. These stages were frequently
      observed within membrane-bound cytoplasmic vacuoles. Hexagonal phage-like
      particles in the cytoplasm of RLOs were also observed.

PMID- 15261772
TI  - Phylogenetic relationships of three new microsporidian isolates from the
      silkworm, Bombyx mori.
AB  - The pathogenicity, mode of transmission, tissue specificity of infection and the
      small subunit rRNA (SSU-rRNA) gene sequences of the three new microsporidian
      isolates from the silkworm Bombyx mori were studied. Out of the three, NIK-2r
      revealed life cycle features and SSU-rRNA gene sequence similar to Nosema
      bombycis, suggesting that it is N. bombycis. The other two, NIK-4m and NIK-3h,
      differed from each other as well as from N. bombycis. NIK-4m was highly
      pathogenic and did not show any vertical transmission, in accordance with the
      apparent lack of gonadal infection, whereas NIK-3h was less pathogenic and
      vertical transmission was not detected but could not be excluded. Phylogenetic
      analysis based on SSU-rRNA gene sequence placed NIK-3h and NIK-4m in a distinct
      clade that included almost all the Vairimorpha species and Nosema species that
      infect lepidopteran and non-lepidopteran hosts, while NIK-2r was included in a
      clade containing almost all the Nosema isolates that infect only lepidopteran
      hosts. Thus, we have presented molecular evidence that one of the three isolates
      is in fact the type species N. bombycis, while the other two isolates are
      Vairimorpha spp. There was distinct separation of microsporidian isolates
      infecting only lepidopteran hosts and those infecting lepidopteran and non
      lepidopteran hosts, reflecting possible co-evolution of hosts and microsporidian
      isolates.

PMID- 15261773
TI  - A nucleopolyhedrovirus from Uranotaenia sapphirina (Diptera: Culicidae).
AB  - In this report we present data on biology, gross pathology, ultrastructure, and
      host range studies of a naturally occurring nucleopolyhedrovirus from the
      mosquito Uranotaenia sapphirina (UrsaNPV). Development of this virus was
      restricted to nuclei of epithelial cells in posterior midgut and distal gastric
      caecum. Occlusion bodies contained numerous singly enveloped rod-shaped virions.
      Early occlusion bodies were irregularly shaped and seemed to subsequently
      coalesce to form larger polyhedra. Mature occlusion bodies had a unique dumbbell
      shape, and lacked a polyhedron envelope and crystalline structure. Developmental
      and structural features of UrsaNPV were generally similar to other mosquito NPVs,
      with major differences in occlusion body shape and size. Transmission tests
      showed that only members of Uranotaenia (Ur. sapphirina and Ur. lowii) were
      susceptible to this virus. Transmission was facilitated by magnesium. Field
      collected Ur. sapphirina larvae had a relatively high rate of dual infections
      with UrsaNPV and UrsaCPV (cypovirus).

PMID- 15261774
TI  - Factors affecting the toxicity of Bacillus thuringiensis var. israelensis and
      Bacillus sphaericus to fourth instar larvae of Chironomus tepperi (Diptera:
      Chironomidae).
AB  - Laboratory bioassays (48h duration, 25+/-1 degrees C) were used to determine the
      toxicity of Bacillus thuringiensis var. israelensis (B.t.i.) and Bacillus
      sphaericus to fourth instar larvae of Chironomus tepperi, a major pest of rice in
      southern Australia. Bioassays were conducted using different combinations of
      larval ages and densities to determine if these factors affected toxicity. The
      effects of temperature and substrate type on B.t.i. toxicity were also
      investigated. Tests were conducted using a commercial B.t.i. formulation
      (VectoBac WDG, 3000ITU/mg), a spore/crystal mixture derived from the VectoBac WDG
      strain, and VectoLex WDG, a commercial B. sphaericus formulation (650ITU/mg).
      VectoBac WDG was highly toxic to fourth instar C. tepperi in bioassays using a
      sand substrate (LC(50) 0.46mg/L, older larvae); younger fourth instar larvae were
      more susceptible (LC(50) 0.20mg/L). Increasing larval densities (from 10 to 30
      per bioassay cup) increased LC(50) values for both age groups, significantly so
      in the case of older larvae (higher density LC(50) 0.80mg/L). Use of a soil
      substrate increased the LC(50) value (older larvae, 10 per cup) to 0.99mg/L.
      Similar differences in toxicity relative to larval age and substrate type were
      found in bioassays using the B.t.i. spore/crystal mixture. VectoBac WDG and the
      spore/crystal mixture both showed similar (approximately 6-fold) declines in
      activity between 30 and 17.5 degrees C. At lower temperatures (between 17.5 and
      15 degrees C), activity of the spore/crystal mixture declined much more rapidly
      than that of VectoBac WDG. VectoLex WDG showed very low toxicity to C. tepperi
      larvae, and the overall impact of larval age and density was relatively minor
      (LC(50) values 1062-1340mg/L). Autoclaving VectoLex WDG did not substantially
      reduce its toxicity (LC(50) 1426mg/L), suggesting that formulation additives
      (i.e., surfactants and other adjuvants) are responsible for much of the toxicity
      occurring at the high product concentrations required to cause C. tepperi
      mortality. Whilst VectoLex WDG was ineffective against C. tepperi, VectoBac WDG
      has the potential to provide selective control of this rice pest at economically
      viable application rates.

PMID- 15261775
TI  - Multiple displacement amplification in combination with high-fidelity PCR
      improves detection of bacteria from single females or eggs of Metaseiulus
      occidentalis (Nesbitt) (Acari: Phytoseiidae).
AB  - Amplifying microbial DNA by the polymerase chain reaction (PCR) from single
      phytoseiid mites has been difficult, perhaps due to the low titer of bacteria and
      to interference by the relatively larger amounts of mite genomic DNA. In this
      paper we evaluate the efficiency of standard and high-fidelity PCR protocols
      subsequent to amplification of the whole genome by a multiple displacement
      amplification (MDA) procedure developed by Dean et al. DNA from the phytoseiid
      Phytoseiulus persimilis (Athias-Henriot) was tested because it lacks a Cytophaga
      like organism (CLO) and we could add known amounts of a plasmid containing a
      cloned 16S rRNA gene fragment from a CLO from Metaseiulus occidentalis (Nesbitt).
      P. persimilis genomic DNA was mixed with the serially diluted plasmid and
      amplified using MDA followed by either standard or high-fidelity PCR. MDA
      followed by high-fidelity PCR was most efficient and successfully amplified an
      expected 1.5-kb band from as little as 0.01fg of the plasmid, which is equivalent
      to about 1 copy. MDA followed by high-fidelity PCR also consistently amplified
      Wolbachia- or CLO-specific products from naturally infected single females or
      eggs of M. occidentalis, which will allow detailed studies of infection frequency
      and transmission of several microorganisms associated with this predatory mite.

PMID- 15261776
TI  - Sitobion avenae alatae infected by Pandora neoaphidis: their flight ability, post
      flight colonization, and mycosis transmission to progeny colonies.
AB  - Epizootics caused by the obligate Entomophthorales pathogen Pandora neoaphidis
      may result from more than one possible means of fungal dissemination among host
      aphids, but we hypothesize that wide dispersal of the fungus is most likely to be
      associated with the flight behavior of migratory alates. We tested this
      hypothesis in a simulation experiment by assessing the flight capability of
      Sitobion avenae alates infected with P. neoaphidis and the potential of their
      post-flight survival, colonization, and mycosis transmission to progeny. A total
      of 281 alates were inoculated with P. neoaphidis, individually flown for up to 5h
      and 9km in a computer-monitored flight mill system and then reared for 10 days on
      wheat seedlings. The infected alates were capable of surviving on average for 2.9
      days (range 1-7 days) and leaving 4.6 nymphs prior to deaths. Transmission of
      fungal infection within progeny colonies occurred after the mother alates died
      from P. neoaphidis mycosis. The level of contagious infection among the nymphs
      reached up to 16.8% within 7 days but varied with the survival time of the
      infected mother alates after flight. Based on stepwise polynomial regression
      analysis, progeny colony size was highly correlated with the interactions of
      flight time with both post-flight survival time and the number of nymphs left per
      alate before death (r2 = 0.997). Progeny mortality on day 5 after colonization
      was inversely correlated with post-flight survival time (r2 = 0.949) whereas
      infection on day 7 was correlated with flight distance and an interaction of post
      flight survival time with fecundity of the infected alates (r2 = 0.970). Progeny
      mortality observed on day 10 was merely correlated to mortality observed on day 5
      (r2 = 0.946). These results indicate a successful transmission of alate-borne P.
      neoaphidis to progeny colonies and further support our hypothesis on the means of
      primary dispersal of aphid epizootics by migratory alates in a geographically
      wide range.

PMID- 15261777
TI  - Discovery of a granulovirus of Pandemis pyrusana (Lepidoptera: Tortricidae), a
      leafroller pest of apples in Washington.
AB  - Pandemis pyrusana (Kearfott) is an important leafroller pest of apples in
      Washington. Surveys for natural enemies discovered a pathogen infecting Pandemis
      leafrollers in an apple orchard in central Washington. The pathogen was
      propagated in the laboratory and light microscopy using an azan stain
      demonstrated that it infected fat body, epidermis, and tracheal matrix cells. The
      virus was identified morphologically as a granulovirus using electron microscopy
      and designated PpGV. Rates of infection were determined for each generation in an
      apple orchard for three years. Infection rates were variable and ranged from 2.6
      to 67% of individuals collected from each generation.

PMID- 15261778
TI  - The long-term effects of DDT exposure on semen, fertility, and sexual function of
      malaria vector-control workers in Limpopo Province, South Africa.
AB  - Hormonally active chemicals in the environment such as DDT have been associated
      with declining male reproductive health, especially semen quality. A cross
      sectional study of 60 workers was performed near the Malaria Control Center (MCC)
      in Tzaneen, Limpopo Province, South Africa. Tests included a questionnaire
      (sexual function, fertility, and job history), a physical examination of the
      reproductive system, and semen analysis (produced via coitus interruptus or
      masturbation). Sperm count, density, and motility using the World Health
      Organization criteria and morphology using the strict Tygerberg criteria were
      determined. Serum o'p' and p'p' isomers of DDE, DDT, and DDD were measured. Forty
      eight (81.0%) participants produced a semen sample, while all completed the
      questionnaires and physical examination. The mean sperm count was 93.8+/-130.3
      million, and sperm density was 74.6+/-85.1 million/mL. The mean normal morphology
      score was 2.5+/-1.8% of subjects. Eighty-four percent of morphology scores were
      below either the WHO or the Tygerberg criteria, with the highest individual score
      being 6%. Self-perceived current problems with sexual function ranged between 10%
      and 20%. The most prevalent genital abnormality was abnormal testis disposition
      at 71%. There were few significant associations between DDT exposure measures
      (measured as years worked at MCC and serum DDT) and reproductive outcomes. p'p'
      DDT was negatively associated with semen count (beta=-3.7+/-1.7; P=0.04; R2=0.05
      adjusted for age, abstinence, physical abnormality, and fever in last 2 months).
      While the semen quality in the study was less than normal, no strong evidence for
      a DDT effect was found.

PMID- 15261779
TI  - The hormonal effects of long-term DDT exposure on malaria vector-control workers
      in Limpopo Province, South Africa.
AB  - DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] compounds, used in many
      developing countries, including South Africa, for the control of malaria vectors,
      have been shown to be endocrine disruptors in vitro and in vivo. The study
      hypothesis was that male malaria vector-control workers highly exposed to DDT in
      the past should demonstrate clinically significant exposure-related anti
      androgenic and/or estrogenic effects that should be reflected in abnormalities in
      reproductive hormone levels. A cross-sectional study of 50 workers from three
      camps situated near the Malaria Control Center (MCC) in Tzaneen was performed.
      Tests included blood sampling before and after a gonadotropin-releasing hormone
      (GnRH) challenge (100 microg). Serum o'p' and p'p' isomers of DDE, DDT, and DDD
      and basal and post-GnRH challenge hormone levels, including luteinizing hormone,
      follicle-stimulating hormone, testosterone, sex hormone-binding globulin,
      estradiol (E2), and inhibin, were measured. The mean number of years worked at
      the MCC was 15.8+/-7.8 years and the mean serum DDT was 94.3+/-57.1 microg/g of
      lipid. Mean baseline E2 levels (62.4+/-29.9 pg/mL) exceeded the laboratory
      reference range. Associations between DDT exposure measures (years worked at the
      MCC and DDT compounds) and hormonal outcomes were weak and inconsistent. The most
      important finding was a positive relationship of baseline E2 and baseline
      testosterone with DDT compounds, especially with p'p'-DDT and -DDD. The strongest
      association found, adjusted for age and SHBG, was between baseline estradiol and
      p'p'-DDT (beta=1.14+/-0.33 pg/mL/microg/ g lipid, P=0.001, R2=0.31, n=46). An
      overall anti-androgenic mechanism best explains the results, but with a number of
      inconsistencies. Associations might be due to chance, as multiple comparisons
      were made. The results therefore do not suggest an overt anti-androgenic or
      estrogenic effect of long-term DDT exposure on hormone levels, but correlations
      do exist in a manner that is not understood.

PMID- 15261780
TI  - Exploration of different methods for measuring DDT exposure among malaria vector
      control workers in Limpopo Province, South Africa.
AB  - DDT compounds are used in many developing countries, including South Africa, for
      the control of malaria vectors. This study investigated biological exposures
      among workers in relation to job history. A cross-sectional study of 59 workers
      at the Malaria Control Centre (MCC) in Tzaneen, South Africa, was performed.
      Tests included a job history questionnaire and the measurement of serum o'p' and
      p'p' isomers of DDE, DDT, and DDD, corrected for serum total lipids. Forty-seven
      (80%) workers donated a blood sample for the determination of serum DDT. The mean
      number of years worked at the MCC (malaria years) was 15.8+/-7.8 years and the
      mean serum DDT was 94.3+/-57.1 microg/g of lipid. There were no significant
      associations between short-to-medium-term serum DDT exposure measures (o'p'-DDE
      and o'p' and p'p' isomers of DDD and DDT) and malaria years. The long-term
      exposure measure, p'p'-DDE, was significantly associated with malaria years
      (beta=3.0+/-1.2 microg/g lipid/year; P=0.001; n=47; adjusted for age), but only
      27% variance of p'p'-DDE was explained. Blood total DDT uncorrected for lipid
      content was strongly related to corrected levels (B=0.74+/-0.48, P=0.00,
      R2=0.77), but uncorrected p'p'-DDE had a weaker association (B=0.0024+/-0.0013,
      P=0.074; R2=0.53) with malaria years than did corrected levels (beta=0.042+/
      0.017; P=0.016; R2=0.56). The results show that serum DDT levels for malaria
      vector-control workers in South Africa with a long-term spraying history are
      high. Job history information on DDT exposures must be very detailed in order to
      provide valid estimates of exposure.

PMID- 15261781
TI  - Exposure to methylmercury in non-fish-eating people in Sweden.
AB  - The extensive use of fish meal as a source of protein for poultry and swine may
      lead to additional exposure to methylmercury (MeHg). We determined the
      concentration of MeHg and inorganic mercury (I-Hg) in blood and total mercury (T
      Hg) in hair in 27 persons (9 men and 18 women, 20-58 years of age) who stated
      that they had consumed no fish for a period of 2 years or more. The participants
      answered a food frequency questionnaire and reported their number of dental
      amalgam fillings. The MeHg concentrations in blood (median, 0.10 microg/L; range,
      0.0-1.0 microg/L) were very low and did not constitute a concern for health
      effects. We also analyzed selenium (Se) in serum. The median concentration was 76
      microg/L (range, 53-103 microg/L), which is in agreement with previous studies of
      the Swedish general population, indicating that the Se status of non-fish-eating
      individuals is not substantially lower than that of people who include fish in
      their diet. We found a significant association (P=0.002) between the number of
      dental amalgam fillings and the I-Hg concentration in blood (median, 0.09
      microg/L; range, 0.03-0.57 microg/L). The T-Hg in hair (median, 0.06 mg/kg;
      range, 0.04-0.32 mg/kg) was significantly associated (R2=0.89; P<0.001) with the
      MeHg in blood, but not with the I-Hg in blood. Therefore, the T-Hg in hair seems
      to reflect MeHg exposure and not I-Hg exposure even in persons with no intake of
      fish.

PMID- 15261782
TI  - Exposure of women to organochlorine pesticides in Southern Spain.
AB  - Organochlorine pesticides are lipophilic compounds that persist in the
      environment. Because of their lipid solubility and resistance to metabolism, some
      of these chemicals accumulate in human tissues. The largest area of intensive
      greenhouse agriculture in Europe is near the Mediterranean coast of Southern
      Spain, where this type of farming has greatly expanded since the 1960s. We
      determined and compared the levels of 15 organochlorine pesticides in the adipose
      tissue and blood of 200 women living in Southern Spain. Aldrin, dieldrin, endrin,
      lindane, methoxychlor, endosulfans, and DDT and its metabolites were identified.
      Detectable concentrations of p,p'-DDE were found in 100% of adipose tissue and
      serum samples. Among the remaining DDTs, p,p'-DDT was the most common, being
      detected in 39% of adipose tissue and 76.5% of serum samples, followed by
      endosulfans I and II, which also were found in both adipose tissue and serum
      samples but at lower concentrations. Endosulfans were followed in frequency by
      lindane, aldrin, and dieldrin. Endrin and methoxychlor were present at a much
      lower frequency compared to those of the other organochlorines. Serum
      concentrations of p,p'-DDE o,p'-DDD, and endosulfan -I, -sulfate, -lactone, and 
      diol were significantly correlated with their adipose tissue concentrations. No
      significant relationships were found between the serum and adipose tissue
      concentrations of the remaining nine compounds determined, raising doubts about
      the equivalent use of fat/serum samples for the exposure assessment of some
      pesticides in epidemiological studies. The results suggested that women of
      reproductive age in Southern Spain have been and are currently exposed to
      organochlorine pesticides. Because many of these chemicals can mobilize during
      pregnancy and lactation, further research is warranted to interpret the health
      consequences for the children of such exposure.

PMID- 15261783
TI  - Association between maternal exposure to elevated ambient sulfur dioxide during
      pregnancy and term low birth weight.
AB  - This retrospective cohort study investigated whether the risk of delivering full
      term (37-44 completed weeks of gestation) low birth weight (LBW) infants is
      associated with differences in exposure to air pollutants in different
      trimesters. Full-term infants (37 completed weeks of gestation) with a birth
      weight below 2500 g were classified as term LBW infants. The study infants
      comprised 92,288 full-term live singletons identified from the Taiwan birth
      registry and born in the city of Taipei or Kaoshiung in Taiwan between 1995 and
      1997. Maternal exposures to various air pollutants including CO, SO2, O3, NO2,
      and PM10 in each trimester of pregnancy was estimated as the arithmetic means of
      all daily measurements taken by the air quality monitoring station nearest to the
      district of residence of the mother at birth. The multivariable logistic
      regression model with adjustment for potential confounders was used to assess the
      independent effect of specific air pollutants on the risk of term LBW. This study
      suggested a 26% increase in term LBW risk given maternal ambient exposure to SO2
      concentration exceeding 11.4 ppb during pregnancy compared to low exposure (<7.1
      ppb) (OR=1.26, 95% CI=1.04-1.53). Since the relative risk of term LBW was
      reassessed according to exposure level in each trimester, mothers exposed to
      >12.4 ppb of SO2 in the last trimester showed 20% higher risk (OR=1.20, 95%
      CI=1.01-1.41) of term LBW delivery than mothers with lower exposure (<6.8 ppb).
      No significant elevation ORs was observed for other air pollutants.

PMID- 15261784
TI  - Selenium in pregnancy: is selenium an active defective ion against environmental
      chemical stress?
AB  - Transportation of selenium from mother to fetus and its possible effects on
      mother's zinc, copper, cadmium, and mercury levels were studied together during
      the first trimester and at term in 216 mothers. Mothers came from three
      geographical places with different selenium intakes. The role of selenium as a
      biomarker for the vital function was estimated by studying the associations
      between tissue or blood selenium content and placental cytochrome P450 enzyme
      activities and the newborn's birth weight. Regardless of the selenium intake of
      the mothers, higher concentrations were found in the cord blood than in mother's
      blood reflecting active transportation of selenium to the fetus. Active smoking
      was associated with higher placental selenium concentrations like it is
      associated with higher placental zinc concentrations. When the cadmium
      concentrations were high in placenta, as in smokers, the transfer of selenium
      from blood to placenta was increased, decreasing the selenium levels in blood. On
      the other hand, the high selenium concentrations in blood were connected to lower
      cadmium concentrations in placenta also in nonsmokers. Selenium had correlations
      with copper and zinc. ECOD activity in placental tissue, mercury in mothers'
      hair, mothers' age, and selenium concentrations in cord blood and placental
      selenium all seem to have connections with xenobiotic-metabolizing enzymes linked
      effects among mothers. These data suggest that selenium has an active role in the
      mother's defense systems against the toxicity of environmental pollutants and the
      constituents of cigarette smoke.

PMID- 15261785
TI  - In vitro effects on macrophages induced by noncytotoxic doses of silica particles
      possibly relevant to ambient exposure.
AB  - The RAW 246.7 macrophage cell line was exposed in vitro to aged crystalline
      silica particles of respirable size for 24 h at a range of doses starting from 15
      microg/2 x 10(6) cells, which is a realistic exposure level of macrophages in the
      airways of ambiently exposed individuals. The particle sample used for the
      experiments was prepared to mimic some aspects of ambient crystalline silica
      particles: size distribution, morphology, and surface reactivity. Our purpose was
      to determine whether a nontoxic quartz load comparable to that of ambient
      exposure would be able to induce macrophage activation and impairment of the
      phagocytic ability, factors altering the lung's capacity to deal with increased
      particle loads (as occurs during high-pollution episodes) or infections and
      affecting the local and systemic responses through the release of biologically
      active compounds (cytokines, reactive oxygen species, NO, isoprostanes). Exposure
      of RAW 264.7 cells to aged silica particles induced macrophage activation
      (evidenced by the morphological features observed with scanning electron
      microscopy and by the release of TNF-alpha and IL-6) and impairment of
      phagocytosis of test particles, even at noncytotoxic doses. The reduction of the
      phagocytic function of the cells after silica treatment was dose-dependent, as
      evidenced by an increase of the population of unphagocytic cells, paralleled by a
      decrease of the actively phagocytizing cell population. We evaluated the
      oxidative stress induced by aged silica particles, quantifying the peroxidation
      products (8-isoprostanes) in the culture media of treated cells, and found a
      strong release at low doses. Isoprostanes are a complex family of compounds which
      have been used as in vivo markers of lipid peroxidation in human disorders, but
      that, as far as we know, have never been evaluated in relation to airborne
      particulate matter exposure. Lipid peroxides are involved in various cellular
      events in the inflammatory response, and isoprostanes are also supposed to exert
      important biological actions on airway and pulmonary vascular smooth muscles and
      on platelets.

PMID- 15261786
TI  - Histopathological changes in the liver, kidneys, and testes of bank voles
      environmentally exposed to heavy metal emissions from the steelworks and zinc
      smelter in Poland.
AB  - Bank voles were trapped in the neighborhood of the Sendzimir steelworks in Krakow
      and the ZGH Boleslaw zinc smelter in Bukowno. The Borecka forest in the north of
      Poland served as a control area. Lead, cadmium, zinc, and iron concentrations
      were analyzed in the liver, kidneys, testes, and femur bones of the bank voles.
      Typically, high levels of lead and cadmium were found in the bones and kidneys,
      respectively. In the femurs of the rodents from Bukowno, 109.26 microg g(-1) dry
      weight of lead was detected. The kidneys of these animals had accumulated 32.98
      microg g(-1) cadmium. Concentrations of zinc and iron in the tissues were at
      physiological levels. No damage was found in the tissues of the bank voles from
      the Borecka forest or in the testes of animals from other areas.
      Histopathological changes in the kidneys of the rodents from Krakow as well as
      changes to the liver and kidneys of the animals from Bukowno were demonstrated.

PMID- 15261787
TI  - Potential assessment of a neural network model with PCA/RBF approach for
      forecasting pollutant trends in Mong Kok urban air, Hong Kong.
AB  - The forecasting of air pollutant trends has received much attention in recent
      years. It is an important and popular topic in environmental science, as concerns
      have been raised about the health impacts caused by unacceptable ambient air
      pollutant levels. Of greatest concern are metropolitan cities like Hong Kong. In
      Hong Kong, respirable suspended particulates (RSP), nitrogen oxides (NOx), and
      nitrogen dioxide (NO2) are major air pollutants due to the dominant usage of
      diesel fuel by commercial vehicles and buses. Hence, the study of the influence
      and the trends relating to these pollutants is extremely significant to the
      public health and the image of the city. The use of neural network techniques to
      predict trends relating to air pollutants is regarded as a reliable and cost
      effective method for the task of prediction. The works reported here involve
      developing an improved neural network model that combines both the principal
      component analysis technique and the radial basis function network and forecasts
      pollutant tendencies based on a recorded database. Compared with general neural
      network models, the proposed model features a more simple network architecture, a
      faster training speed, and a more satisfactory prediction performance. The
      improved model was evaluated with hourly time series of RSP, NOx and NO2
      concentrations monitored at the Mong Kok Roadside Gaseous Monitory Station in
      Hong Kong during the year 2000 and proved to be effective. The model developed is
      a potential tool for forecasting air quality parameters and is superior to
      traditional neural network methods.

PMID- 15261788
TI  - Dioxin-like components in human breast milk collected from Hong Kong and
      Guangzhou.
AB  - The H4IIE rat hepatoma cell line was employed as a cell model to screen 7
      ethoxyresorufin O-deethylase (EROD)-TCDD equivalents (EROD-TEQ) of human breast
      milk samples collected from Hong Kong and Guangzhou, China. The screening methods
      employed a 96-well plate spectrofluorometer-EROD assay. For cell-line validation,
      our results demonstrated a dose-dependent increase in the Ah receptor-mediated
      response (i.e., CYP1A1 mRNA and EROD) of the cells upon exposure to a number of
      known Ah receptor agonists, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      2,3,7,8-tetrachlorodibenzothiophene, benzo[a]pyrene, and beta-naphthaflavone.
      TCDD induced CYP1A1 mRNA and EROD was in a close positive correlation (r=0.98).
      For the screening of dioxin-like compounds, breast milk samples collected during
      lactation weeks 3-5 were used. One hundred (from Hong Kong) and 48 (from
      Guangzhou) breast milk samples were assayed, of which 65% and 68% of the samples,
      respectively, showed detectable dioxin-like activities using the H4IIE cell EROD
      screening method. For sixty-five samples from Hong Kong the mean EROD-TEQ values
      ranged from 58.1 to 96.5 pg/g of milk fat for those aged 21-36 years while 32
      samples from Guangzhou had mean values of 98.8-202.1 pg/g of milk fat. In
      comparisons of the EROD-TEQ values for different age groups from both cities,
      there were no significant differences (P<0.05). However, the mean and median EROD
      TEQ values of the Guangzhou population were in general higher than those of the
      Hong Kong population. The results of the present study indicate that it is
      feasible to use the H4IIE cell-line as a model for screening dioxin-like
      compounds in human breast milk. In addition, the method is rapid and cost
      effective, particularly for a routine and high-throughput sample screening
      analysis, compared to the costly and time-intensive chemical analytical
      techniques.

PMID- 15261789
TI  - The relationship between lysosomal biomarker and organismal responses in an acute
      toxicity test with Eisenia Fetida (Oligochaeta) exposed to the fungicide copper
      oxychloride.
AB  - The LC50 of copper oxychloride for Eisenia fetida was determined, and its effects
      on biomass change and lysosomal damage using neutral red retention times (NRRT)
      of coelomocytes were measured. The aim was to establish whether a lysosomal
      subcellular response, measured as NRRT, could be linked to the LC50 and biomass
      changes. Further, we attempted to establish the ecological relevance of the LC50
      by comparing it to studies previously carried out on the effects of copper
      oxychloride on field earthworm populations. The experiment was conducted over a
      period of 28 days, during which the earthworms were exposed to different
      concentrations of copper oxychloride in artificial soil. The calculated LC50 was
      883 microg g(-1) for copper oxychloride and 519 microg g(-1) for copper. Results
      indicated that changes in coelomocyte membrane stability manifested earlier than
      effects on biomass. Since the NRRT assay was very sensitive and generated an
      early response before changes in biomass or mortality could be measured, it may
      have predictive value and may contribute information during acute toxicity tests,
      which could be of greater ecological relevance than mortality data alone.

PMID- 15261790
TI  - Fruits, fish, and mercury: further considerations.

PMID- 15261792
TI  - Respiratory impairment due to asbestos exposure in brake-lining workers.

PMID- 15261794
TI  - Single maxillary complete denture.
AB  - The single maxillary denture is a complex prosthesis that requires a complete
      understanding of the basics of denture occlusion. Theilemann's formula must be
      applied to each individual patient, and appropriate treatment must be taken to
      assure complete balance in all excursive movements. The basic principles of
      retention, stability, and support should not to be taken for granted, and steps
      must be completed so that all components are working in harmony for success of
      the maxillary denture. Treatment of various patients has been illustrated to
      allow the reader to comprehend better the modalities that can be employed for
      preparing the oral environment before denture insertion thereby ensuring better
      success in treating these classes of patients.

PMID- 15261795
TI  - Implant-retained maxillary overdentures.
AB  - Overdentures supported by osseointegrated implants overcome many of the
      complications observed with overdentures supported by natural teeth. Dental
      implants are free of biologic consequences associated with natural teeth, such as
      dental caries and periodontal disease. Bone undercuts adjacent to implants do not
      mimic those found adjacent to natural tooth roots. Implants are used to provide
      predictable retention, support, and stability for overdenture prostheses. When
      lip or facial support is required, the overdenture is the treatment of choice.
      Likewise the overdenture may improve phonetic deficiencies associated with
      alveolar bone loss.

PMID- 15261796
TI  - The mandibular complete overdenture.
AB  - Mandibular complete overdenture treatment has been available for decades, but its
      use was limited when the treatment relied on retained teeth as overdenture
      abutments. This treatment, however, is currently experiencing more popularity
      than ever before. In fact, dentistry may be experiencing a philosophical shift,
      in which mandibular implant overdenture treatment may become the new standard of
      care for the treatment of the edentulous mandible. Practitioners are looking for
      simplified treatments that can provide cost-effective alternatives to more
      complex implant prosthodontic procedures. Implant overdentures provide a strong
      return for the investment in treatment time and expense and are a treatment
      suited to the lower socioeconomic status of many edentulous patients. The
      clinical outcome of this treatment is significantly better than that achieved
      with conventional mandibular dentures, especially when patients are experiencing
      technical problems because of compromised prosthesis retention or stability.

PMID- 15261797
TI  - Simplified complete dentures.
AB  - Complete denture fabrication can be an enjoyable and profitable facet of a dental
      practice. The key to success is a thorough diagnosis, understanding the patient's
      desires and expectations, and following a standardized sequence of treatment.
      This article describes a modified complete denture technique designed to minimize
      chair time but maintain sound principles of denture construction.

PMID- 15261798
TI  - Complete denture occlusion.
AB  - Lingualized articulation has been advocated by many practitioners over the past
      60 years. It can be achieved using a variety of tooth molds arranged in a number
      of ways that seem to provide the least complicated approach to occlusal
      rehabilitation and to satisfy the needs of the edentulous patient. Clinical
      experience has supported its use during functional and nonfunctional activities
      [17, 18]. The different combinations of tooth molds available from one particular
      tooth manufacturer, and now specific molds designed for lingualized articulation
      by other manufacturers, allows the practitioner to improve the likelihood of
      maximal intercuspation, avoid deflective occlusal contacts, determine cusp height
      for selective occlusal reshaping, and achieve a natural and pleasing appearance.
      The articulation and arrangement of the posterior teeth in lingualized
      articulation assures a standardized arrangement.

PMID- 15261800
TI  - The milled surface as a precision attachment.
AB  - The creation of paralleled, milled surfaces in natural or restored abutment
      teeth, coupled with removable partial denture castings that have optimal contact
      with these preparations, results in a path of insertion and removal that is
      controlled in a manner similar to one using conventional precision attachments.
      Because the milled surfaces are primarily extracoronal, little if any, additional
      tooth reduction is required for adequate mouth preparation. Avoiding additional
      tooth reduction minimizes later abutment fracture. The great increase in
      stability and resistance to rotational movements, when combined with conventional
      posterior clasping, provides a reasonable alternative to the precision attachment
      in providing maximal esthetics for the partially edentulous patients.

PMID- 15261799
TI  - Removable partial denture occlusion.
AB  - No single occlusal morphology, scheme, or material will successfully treat all
      patients. Many patients have been treated, both successfully and unsuccessfully,
      using widely varying theories of occlusion, choices of posterior tooth form, and
      restorative materials. Therefore, experience has demonstrated that there is no
      one righ r way to restore the occlusion of all patients. Partially edentulous
      patients have many and varied needs. Clinicians must understand the healthy
      physiologic gnathostomatic system and properly diagnose what is or may become
      pathologic. Henderson [3] stated that the occlusion of the successfully treated
      patient allows the masticating mechanism to carry out its physiologic functions
      while the temporomandibular joints, the neuromuscular mechanism, the teeth and
      their supporting structures remain in a good state of health. Skills in diagnosis
      and treatment planning are of utmost importance in treating these patients, for
      whom the clinician's goals are not only an esthetic and functional restoration
      but also a lasting harmonious state. Perhaps this was best state by DeVan [55]
      more than 60 years ago in his often-quoted objective. "The patient's fundamental
      need is the continued meticulous restoration of what is missing, since what is
      lost is in a sense irretrievably lost." Because it is clear that there is no one
      method, no one occlusal scheme, or one material that guarantees success for all
      patients, recommendations for consideration when establishing or reestablishing
      occlusal schemes have been presented. These recommendations must be used in
      conjunction with other diagnostic and technical skills.

PMID- 15261801
TI  - Soft liners.
AB  - The article provides a background for understanding the properties of soft liner
      materials, describing associated problems, and discussing clinical applications
      of soft liners in dental practice. Although not a panacea, soft liner materials
      provide the practitioner with a variable tool in providing excellent clinical
      care for patients.

PMID- 15261802
TI  - Denture adhesives.
AB  - An attempt has been made to present an overview of this controversial topic of
      over-the-counter denture adherents. The proper use of a denture adhesive can
      truly provide both dentist and patient with a means of securing a prosthesis
      despite the practitioner's best efforts. It is through a thorough knowledge of
      the attributes and limitations of these products that the dental profession can
      better guide patients in the management of their prosthesis.

PMID- 15261803
TI  - Prosthodontic management of ridge deficiencies.
AB  - The treatment goals in prosthodontics and dental laboratory technology are to
      provide patients with long-term predictable and esthetic outcomes. The
      periodontal tissues define the framework that will maintain ridge height,
      thickness, color, texture, and gingival-tooth frame. The loss of teeth, residual
      ridge resorption and the loss of gingival tissues continue to affect long-term
      and esthetic treatment outcomes. Prosthodontic treatment requires consideration
      of the potential negative tissue effect that time and normal biologic change
      might have on the completed prosthetic design. This article describes alternative
      restorative solutions for clinical conditions that have traditionally been
      managed by surgery, removable prosthodontics, or esthetically compromised fixed
      restorations. Different clinical conditions for tooth-retained and implant
      retained fixed partial dentures as well as the laboratory technology describing
      construction of these different restorations will be discussed.

PMID- 15261805
TI  - Liquid chromatography method for quantifying N-(4-hydroxyphenyl)retinamide and N
      (4-methoxyphenyl)retinamide in tissues.
AB  - A simple and accurate high-performance liquid chromatography (HPLC) method was
      developed to measure levels of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR)
      and its main metabolite N-(4-methoxyphenyl)retinamide (4-MPR) in tissue.
      Following ultrasonic extraction of fresh tissue in acetonitrile (ACN), 4-HPR and
      4-MPR were measured by HPLC with UV absorbance detection at 340 nm, using
      isocratic elution with ACN, H(2)O, and acetic acid. N-(4-ethoxyphenyl)retinamide
      (4-EPR) was employed as an internal standard. The 4-HPR and 4-MPR recovery in
      bovine liver or bovine brain tissue samples spiked with known amounts of 4-HPR
      and 4-MPR ranged from 93 to 110%. The detection limit of the method was 50 ng/ml.
      The method was tested on actual samples from an athymic (nu/nu) mouse carrying a
      subcutaneous tumor xenograft originating from SMS-KCNR neuroblastoma cells. The
      tissues were harvested and analyzed following a 3 day long treatment with
      intraperitoneal injections of 4-HPR/Diluent-12. 4-HPR and the metabolite 4-MPR
      were detected and quantitated in the tested tissues including tumor, liver, and
      brain. This method can be used to quantify 4-HPR and 4-MPR in different tissues
      to determine the bioavailability of 4-HPR.

PMID- 15261806
TI  - Determination of dihydroergocryptine in human plasma and urine samples using on
      line sample extraction-column-switching reversed-phase liquid chromatography-mass
      spectrometry.
AB  - A rapid and sensitive assay for the determination of dihydroergocryptine (DHEC)
      in human plasma and urine samples with dihydroergotamine (DHET) as the internal
      standard was developed. The procedure employs on-line sample preparation using an
      extraction pre-column and an octadecylsilylsilica (ODS) analytical column. After
      centrifugation human plasma or urine were injected onto the pre-column,
      concentrated and extracted, back-flushed onto the analytical column and eluted
      with a binary methanol--aqueous formic acid gradient. Either determination of
      DHEC as well of its mono- and dihydroxy-metabolites was performed by measurement
      of the signal responses from MS detection in the selected reaction monitoring
      (SRM) mode using the transition of the respective parent ions to the common
      daughter ion at m/z=270.2 amu. The limit of quantitation (LOQ) for determinations
      of DHEC in both plasma and urine were 25 pg/ml for injected sample volumes of 400
      microl. Proportionality of signal responses versus concentration was accomplished
      within the range of 25-1000 pg/ml. Recovery of target analyte from plasma was
      99%. Mean values of the coefficients of variation (CV) for the target analyte in
      plasma ranged from 1.7 to 13.8% (within-day) and 5.0 to 9.1% (between-day) and
      accuracy from 91.7 to 102.6% for the within-day and from 95.8 to 98.8% for the
      between-day measurements. The corresponding values for determinations in urine
      were 1.7-14.5% (within-day) and 5.3-11.8% (between-day) for CV and 95.8-110.7%
      (within-day) and 100.1-104.6% (between-day) for accuracy.

PMID- 15261807
TI  - Quantification of Doxorubicin and metabolites in rat plasma and small volume
      tissue samples by liquid chromatography/electrospray tandem mass spectroscopy.
AB  - The anthracycline Doxorubicin (DXR) is used widely for the treatment of human
      malignancies, and drug delivery technologies are under investigation to enhance
      antitumor selectivity and effectiveness. A liquid chromatography-tandem mass
      spectroscopy (LC-MS/MS) method was developed to identify and quantify DXR and key
      metabolites in small-volume biological samples. The assay was linear over the
      therapeutically relevant concentration range (0.125-10,000 nM); in brain tissue,
      the lower limit of quantification was 0.247 nM and the sensitivity was 1.4 pg.
      The ability to quantify DXR and detect metabolite formation may provide insight
      into the toxicity and bioavailability of drug incorporated into carriers such as
      liposomes.

PMID- 15261808
TI  - Unified gas chromatographic-mass spectrometric method for quantitating tyrosine
      metabolites in urine and plasma.
AB  - Tyrosine and many of its catabolites play significant roles in the in the
      toxicity associated with acquired and congenital forms of hypertyrosinemia. We
      now report a specific and sensitive GC/MS method for the simultaneous
      determination of tyrosine metabolites maleylacetone (MA), fumarylacetone (FA),
      succinylacetone (SA), fumarate and acetoacetate in urine and plasma. Tyrosine
      metabolites and an internal standard, 2-oxohexanoic acid (OHA), in urine or
      plasma samples were derivatized to their methyl esters with a 12% boron
      trifluoride-methanol complex (12%BF3-MeOH). The reaction mixture was extracted
      with methylene chloride and analyzed by GC/MS, using a selected ion monitoring
      (SIM) mode. The detection limits were in the range of 0.08-0.4 ng and the
      quantitation limits were 0.2-2 ng. Most of the intraday and interday coefficients
      of variation for three concentrations (low, medium and high) of the analytes were
      below 10%. Sensitivity and selectivity are superior to existing HPLC or enzymatic
      methods and derivatization of samples is simpler than the traditional silylation
      of organic acids used for analysis by GC/MS or derivatization to oximes, followed
      by silylation in the case of the ketoacids, such as SA. Furthermore, the current
      procedure can be performed in aqueous solution, which results in a high
      percentage yield without appreciable analyte degradation or formation of side
      products. Thus far, the method has been successfully applied in the analysis of
      over 5000 urine and plasma samples from humans and rodents.

PMID- 15261809
TI  - Liquid chromatographic method for the quantitative determination of Nepsilon
      carboxymethyllysine in human plasma proteins.
AB  - The modification of the lysine moieties of proteins to Nepsilon
      carboxymethyllysine (CML) is supposed to play a major role in the development of
      long-term complications in patients with diabetes mellitus. This paper presents
      an analytical method for the quantitative determination of CML in plasma
      proteins, which could be used for studying the development of diabetic
      complications. The method is based on isolating proteins from plasma by
      precipitation with trichloroacetic acid and hydrolysing these under acidic
      conditions (6M hydrochloric acid at 110 degrees C for 20 h) to the individual
      amino acids. After hydrolysis, CML is derivatised along with the other amino
      acids to 9-fluorenylmethoxycarbonyl (FMOC) derivatives, which are subsequently
      separated by reversed-phase column liquid chromatography using a 150 mm x 4.6 mm
      C8 column and a mobile phase of 25 mM potassium phosphate buffer (pH 2.0) and
      acetonitrile (80:20 (v/v)) and detected using fluorescence detection (excitation
      at 260 nm and emission at 310 nm). Quantification of the protein-bound CML
      content of a plasma sample is achieved using standard addition. The impact of
      several aspects of the sample preparation and chromatography on method
      performance is discussed. Method evaluation results are reported and show that
      this method is capable of determining CML with good accuracy and precision (below
      10%) in the relevant concentration range (1-10 microg/ml), with a limit of
      detection of 0.2 microg/ml.

PMID- 15261810
TI  - On-line coupling of sequential injection with liquid chromatography for the
      automated derivatization and determination of gamma-aminobutyric acid in human
      biological fluids.
AB  - The principle of sequential injection analysis (SIA) was exploited to develop a
      rapid fully automated and efficient pre-column derivatization procedure coupled
      on-line to liquid chromatography (HPLC). Using the SIA-HPLC derivatization
      protocol gamma-aminobutyric acid (GABA) was determined fluorimetrically in human
      biological fluids with o-phthaldialdehyde (OPA) as derivatization reagent and
      minimum sample pretreatment. A lab-built SIA system was used to handle samples,
      standard solutions and OPA reagent. Appropriate volumes of the reagents were
      introduced in the holding coil of the SIA system and were mixed on propulsion to
      the HPLC loop through a suitable reaction coil. The chemical (pH, c(OPA),
      c(mercaptoethanol)) and instrumental variables (volumes of sample and reagent,
      reaction time) of the reaction were studied and optimized in terms of maximum
      sensitivity. The chromatographic variables (gradient composition of the eluent
      and flow rate) were studied for optimum selectivity and peak characteristics. The
      developed experimental configuration facilitated fully-automated operation thus
      minimizing errors in handling. Additionally the method as a whole provided very
      satisfactory sensitivity, precision and accuracy. Direct determination of GABA in
      human urine and cerebrospinal fluid (CSF) at microg L(-1) (ppb) levels was
      accomplished, with minimum sample pretreatment.

PMID- 15261811
TI  - Liquid chromatographic method for determination of four active saponins from
      Panax notoginseng in rat urine using solid-phase extraction.
AB  - Four major active saponins (ginsenosides Rg1, Rb1, Rd and notoginsenoside R1) in
      Panax notoginseng were determined in rat urine after oral and intravenous
      administration of total saponins of P. notoginseng (PNS), and the urine samples
      were treated with solid-phase extraction (SPE) prior to liquid chromatography. A
      reversed-phase liquid chromatography system with ultraviolet detection and a
      Zorbax SB-C18 column was used. The within-day and between-day assay coefficients
      of variation for the four saponins in urine were less than 7% and the recovery of
      this method was higher than 85%. Using this method, the excretion profile of the
      drug in rat urine after administration of PNS was revealed for the first time.

PMID- 15261812
TI  - Expressional pattern of known and predicted signaling proteins in seven human
      cell lines.
AB  - Although a variety of signaling systems and signaling proteins have been
      described, cell specific expression of these structures has not yet been
      systematically studied. Human amnion, bronchial epithelial, fibroblast, glial,
      kidney, lymphocyte and mesothelial cells were subjected to two-dimensional-gel
      electrophoresis followed by analysis of protein spots by MALDI-TOF and subsequent
      identification by specific software. A series of well-documented signaling
      proteins showed cell specific expressional patterns. Five hypothetical proteins-
      hypothetical 37.5 kDa protein, similar to calsyntenin 1, hypothetical armadillo
      repeat/plakoglobulin ARM-repeat profile containing protein, 11 days embryo cDNA
      clone 2700084k13, hypothetical protein flj22171--so far predicted from their
      nucleic acid sequence only, were identified, complementing already reported
      signaling cascades. An analytical tool for the concomitant determination of a
      large series of signaling structures by an antibody independent protein-chemical
      method is provided.

PMID- 15261813
TI  - Gas chromatography-mass spectrometry determination of matrine in human plasma.
AB  - A method was developed for the quantification of matrine in human plasma using a
      liquid-liquid extraction procedure followed by gas-chromatography-mass
      spectrometry (GC/MS) analysis. Deuterated matrine, an internal standard of the
      analysis, was spiked into the plasma samples before extraction. Linear detection
      responses were obtained for matrine concentrations ranging from 10 to 500 ng/ml.
      The intra-day and inter-day precision ranged from 0.4 to 4.0% and 1.0-3.5%,
      respectively. The intra-day accuracy was between -7.3 and 4.5%. The limit of
      quantification for matrine was 23 ng/ml. The extraction efficiency averaged about
      38%. The validated GC/MS method will be used to quantify matrine in human plasma
      samples collected in a clinical trial study.

PMID- 15261814
TI  - Rapid and sensitive liquid chromatography-tandem mass spectrometric method for
      the quantitation of metformin in human plasma.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS-MS)
      method for the determination of metformin in human plasma using phenformin as
      internal standard has been developed and validated. Sample preparation of plasma
      involved acidification with acetic acid, deproteination with acetonitrile and
      washing with dichloromethane. Samples were then analyzed by HPLC on a short
      Nucleosil C18 column (5 microm, 50 mm x 4.6 mm i.d.) using a mobile phase
      consisting of acetonitrile:methanol:10mM ammonium acetate pH 7.0 (20:20:60,
      v/v/v) delivered at 0.65 ml/min. Detection was performed using an Applied
      Biosystems Sciex API 4000 mass spectrometer set at unit resolution in the
      multiple reaction monitoring (MRM) mode. Atmospheric pressure chemical ionization
      (APCI) was used for ion production. The assay was linear over the range 1-2000
      ng/ml with intra- and inter-day precision of <8.6% and accuracy in the range 91
      110%. The limit of detection was 250 pg/ml in plasma. The method was successfully
      applied to a clinical pharmacokinetic study of an extended-release tablet of
      metformin hydrochloride (500 mg) administered as a single oral dose.

PMID- 15261815
TI  - Determination of flumazenil in human plasma by liquid chromatography-electrospray
      ionisation tandem mass spectrometry.
AB  - A liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI
      MS/MS) method was developed to determine unlabelled flumazenil (Ro 15-1788) in
      human plasma in [11C]flumazenil positron emission tomography (PET) studies. N
      Methyl tri-deuterated flumazenil was used as an internal standard. The analyte
      and internal standard were extracted from plasma samples using solid-phase
      extraction, with a recovery of 78%. This was determined through the convenience
      of radioactivity measurements of 11C-labelled flumazenil. The evaporated and
      reconstituted eluate was analysed by LC-ESI-MS/MS. The calibration curve was
      linear over the tested concentration range of 0.05-0.5 nM (15-150 pg/ml) with a
      correlation coefficient, R2, of 0.998+/-0.001. A high precision was achieved,
      with mean intra-assay and inter-assay relative standard deviations of at most 6
      and 7%, respectively. The accuracy of the method ranged from 95 to 104%. As a
      proof of concept, the validated method was applied in the determination of
      flumazenil in plasma from two healthy volunteers participating in a PET study
      with three repeated investigations. A bolus-infusion protocol was used to achieve
      a constant concentration level of flumazenil. The average plasma concentrations
      ranged from 0.11 and 0.19 nM and all measurements were within the calibration
      standard range. The flumazenil concentrations were relatively constant within
      each scan and the average intra-scan precision was 15%.

PMID- 15261816
TI  - An estimation of the exposure to organophosphorus pesticides through the
      simultaneous determination of their main metabolites in urine by liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid method has been developed for the determination of 4-nitrophenol (PNP)
      (parathion and methyl-parathion metabolite) and 3-methyl-4-nitrophenol (3-Me-PNP)
      (fenitrothion metabolite) in human urine by coupled-column liquid chromatography
      combined with tandem mass spectrometry (LC-LC-MS/MS). The LC-LC-MS/MS approach
      allows the determination at sub-ppb level of free metabolites by injecting the
      urine directly into the system and the total metabolites after a simple enzymatic
      hydrolysis. The method has been validated, obtaining limits of detection of 0.1
      and 0.2 microg/L for 4-nitrophenol and 3-methyl-4-nitrophenol, respectively.
      Additionally, a multi-residue LC-MS/MS method is proposed in order to evaluate
      the levels of other parathion and methyl parathion metabolites. This approach
      allows the simultaneous determination of dimethyl phosphate (DMP), dimethyl
      thiophosphate (DMTP), 4-nitrophenolsulphate and 4-nitrophenolglucuronide without
      tedious sample treatments. The applicability of both methods is demonstrated by
      applying them to various urine samples from an unexposed population and a grower
      who applied methyl parathion. The combination of both methods allows a general
      overview on the presence of different metabolites (free and conjugated) and the
      concentration ratios between them, giving useful information on organophosphorus
      pesticides metabolism and excretion.

PMID- 15261817
TI  - Determination of single-cell gene expression in Arabidopsis by capillary
      electrophoresis with laser induced fluorescence detection.
AB  - We report a new method for the measurement of gene expression in single cells of
      Arabidopsis using capillary electrophoresis with laser-induced fluorescence (CE
      LIF) detection. Initially, the quantitative analysis of APETALA2 (AP2) and LEAFY
      (LFY) was performed by CE-LIF method. The detection limits of AP2 and LFY can
      reach 0.08 and 0.04 ng/ml (signal-to-noise ratio = 3), respectively. This
      protocol coupling with single-cell reverse transcriptase-polymerase chain
      reaction (SC-RT-PCR) has been used to monitor LFY and AP2 expression in
      individual cells from the shoot apical meristem, leaf, root, and stem of
      Arabidopsis, simultaneously. The effect of PCR cycle number on PCR product
      concentrations has been discussed. The changes of LFY expression were determined
      at single-cell level in different Arabidopsis tissues. The relationship between
      gibberallic acid (GA) and LFY expression was also revealed by this method. It was
      shown that the combination between CE-LIF and SC-RT-PCR could provide a highly
      sensitive and selective tool for the determination of different gene expression
      at single-cell level in specific tiny plant tissues.

PMID- 15261818
TI  - Characterization of spirochetal isolates from arthropods collected in South
      Moravia, Czech Republic, using fatty acid methyl esters analysis.
AB  - Aim of this study was to evaluate cellular fatty acid analysis for
      characterization of spirochetes. Strains were isolated from arthropods collected
      in South Moravia, Czech Republic. Fatty acid methyl esters (FAME) profile was
      determined for five Borrelia burgdorferi sensu lato (s.l.) strains isolated from
      Ixodes ricinus ticks, one "Spironema culicis" strain recovered from mosquito
      Culex pipiens and seven spirochetal strains (not identified yet) isolated from
      mosquitoes and blackflies. Analysis was performed using a gas chromatography
      column in conjunction with Microbial Identification System Sherlock (MIDI Inc.,
      Newark, DE, USA). Results obtained on the basis of cluster analysis of FAME
      profiles showed, that the B. burgdorferi sensu lato isolates could be well
      separated from other spirochetal isolates. We recommended method used in this
      study as a useful tool for preliminary identification of spirochetes isolated
      from ticks and dipterans.

PMID- 15261819
TI  - SdFFF monitoring of cellular apoptosis induction by diosgenin and different
      inducers in the human 1547 osteosarcoma cell line.
AB  - Apoptosis is one of the most important phenomena of cellular biology.
      Sedimentation field flow fractionation (SdFFF) has been described as an effective
      tool for cell separation, respecting integrity and viability. Because SdFFF takes
      advantage of intrinsic properties of eluted cells (size, density, shape or
      rigidity), we investigated the capacity of SdFFF in monitoring the early and
      specific biophysical modifications which occurred during cellular apoptosis
      induction. Then, we used, as an in vitro cellular apoptosis model, the
      association between human 1547 osteosarcoma cells and diosgenin, a plant steroid
      known to induce apoptosis. Four other molecules were studied: hecogenin,
      tigogenin, staurosporine and MG132. Our results demonstrated a correlation
      between SdFFF elution profile changes (peak shape modification and retention
      ratio evolution) and effective apoptosis induction. For the first time, we
      demonstrated that SdFFF could be used to monitor apoptosis induction as early as
      6 h incubation, suggesting different applications such as screening series of
      molecules to evaluate their ability to induce apoptosis, or sorting apoptotic
      cells to study apoptosis pathway.

PMID- 15261820
TI  - Determination of long-chain fatty acid acyl-coenzyme A compounds using liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - Acyl-CoAs have important role in fat and glucose metabolism of the cells. In this
      study we have developed an on-line HPLC-ESI-MS/MS method for determination of
      long-chain acyl-CoA compounds in rat liver samples. Six long-chain acyl-CoAs
      (C16:0, C16:1, C18:0, C18:1, C20:0 and C20:4) were separated with a C4 reversed
      phase column using triethylamine acetate and acetonitrile gradient. Negative
      electrospray ionization is very suitable for acyl-CoA compounds and excellent
      MS/MS spectra for long-chain acyl-CoAs can be obtained. MS/MS method with an ion
      trap mass spectrometer makes it possible to identify and quantitate individual
      acyl-CoAs simultaneously. The method proved to be sensitive enough for
      determination of all compounds of interest using 0.4-0.7 g of tissue and was
      validated in the range of 0.1-15.0 pmol/microl.

PMID- 15261821
TI  - Investigation of volatile biomarkers in lung cancer blood using solid-phase
      microextraction and capillary gas chromatography-mass spectrometry.
AB  - In the present work, solid-phase microextraction (SPME) and gas chromatography
      mass spectrometry (GC-MS) was developed for investigation of lung cancer volatile
      biomarkers. Headspace SPME conditions (fiber coating, extraction temperature and
      extraction time) and desorption conditions were optimized and applied to
      determination of volatiles in human blood. To find the biomarkers of lung cancer,
      investigation of volatile compounds in lung cancer blood and control was
      performed by using the present method. Concentrations of hexanal and heptanal in
      lung cancer blood were found to be much higher than those in control blood. The
      two molecules of hexanal and heptanal were regarded as biomarkers of lung cancer.
      By comparison of volatiles in breath and in blood, it is demonstrated that
      hexanal and heptanal in breath were originated from blood and screening of lung
      cancer by breath analysis be feasible. These results show that SPME/GC-MS is a
      simple, rapid and sensitive method very suitable for investigation of volatile
      disease markers in human blood.

PMID- 15261822
TI  - Proteomic analysis of an orthotopic neuroblastoma xenograft animal model.
AB  - Neuroblastoma is the most common extracranial solid tumour of childhood and
      comprises up to 50% of malignancies among infants. There is a great need of
      designing novel therapeutic strategies and proteome analysis is one approach for
      defining markers useful for tumour diagnosis, as well as molecular targets for
      novel experimental therapies. We started by comparing healthy adrenal glands
      (which are the election organs developing primary neuroblastoma, NB, tumours) and
      adrenal glands carrying primary NB tumours, taken from nude mice. Standard maps
      of healthy and tumour samples were generated by analysis with the PDQuest
      software. The comparison between such maps showed up- and down-regulation of 84
      polypeptide chains, out of a total of 700 spots detected by a fluorescent stain,
      Sypro Ruby. Spots that were differentially expressed between the two groups, were
      analysed by MALDI-TOF mass spectrometry and 14 of these spots were identified so
      far. Among these proteins, of particular interest are the down-regulated proteins
      adrenodoxin (21-folds), carbonic anhydrase III (eight-folds) and aldose reductase
      related protein I (eight-folds), as well as the up-regulated protein peptidyl
      propyl cis-trans isomerase A (five-folds). Moreover new proteins, which were
      absent in control samples, were expressed in tumour samples, such as
      nucleophosmin (NPM) and stathmin (oncoprotein 18).

PMID- 15261823
TI  - Detection of endogenous boldenone in the entire male horses.
AB  - Boldenone (1,2-dehydrotestosterone) is a common veterinary anabolic agent. Its
      structure is very similar to testosterone. Testosterone is endogenous in the
      horse, whereas there has been no report concerning the detection of endogenous
      boldenone. This paper reports the direct observation of sulphate conjugate of
      boldenone in equine urine from entires. The detection procedures involved solid
      phase extraction, immunoaffinity column (IAC) purification, and then LC-MS-MS
      analysis on a Q-ToF instrument. The identification of boldenone sulphate has
      provided direct evidence for the endogenous nature of boldenone in entire male
      horses. Quantification data for the normal level of boldenone in Hong Kong
      racehorses will also be discussed.

PMID- 15261824
TI  - Subcellular metabolite profiles of the parent CCRF-CEM and the derived CEM/C2
      cell lines after treatment with doxorubicin.
AB  - Micellar electrokinetic capillary chromatography with laser-induced fluorescence
      detection was used to detect the differences in doxorubicin metabolite
      accumulation in four subcellular fractions isolated from the CCRF-CEM and the
      CEM/C2 human leukemia cell lines. Five fluorescent metabolites and doxorubicin
      make up the metabolite profile of these cell lines upon treatment with 10 microM
      doxorubicin for 12 h, cell lysis, and fractionation by differential
      centrifugation. Based on the relative electrophoretic mobility of synthetic
      standards, we tentatively identify one metabolite as 7-deoxydoxorubicinone and
      suggest that doxorubicinone is not among those metabolites detected. Although the
      obvious difference between the derived cell line (CEM/C2) and the parent cell
      line (CCRF-CEM) is the decreased topoisomerase I activity in the former, the
      results presented here indicate that each cell line has a unique distribution of
      metabolites in each one of four subcellular fractions: nuclear-enriched, heavy
      organelle-enriched, light-organelle-enriched, and cytoplasmic fractions.

PMID- 15261825
TI  - Temporal expression of L-Maf and RaxL in developing chicken retina are arranged
      into mosaic pattern.
AB  - Members of the maf gene family encode basic/leucine zipper transcription factors
      and play important roles during cell differentiation in vertebrate and Drosophila
      development. To investigate the possible roles of chicken lens-specific Maf (L
      Maf)/MafA in retinal development, we analyzed its expression in the developing
      chicken retina. We first determined that L-Maf is expressed in a subset of
      ganglion cells, amacrine cells and rod cells during retinal development. To
      characterize further the L-Maf expressing cells during photoreceptor development,
      we compared the expression patterns of L-Maf and RaxL, a marker of cone cells. We
      found the L-Maf proteins are detectable from E10 between RaxL positive cone cells
      in outer nuclear layer (ONL). Subsequently, the expression of L-Maf is restricted
      to the innermost nuclear cells in the ONL during rod differentiation. In
      contrast, RaxL positive cone cells are distributed in the outermost layer of ONL.
      Furthermore, tangential retinal sections showed that L-Maf positive rods and RaxL
      positive cones form a mosaic pattern during photoreceptor development.

PMID- 15261826
TI  - Changes in the expression and localization of cohesin subunits during meiosis in
      a non-mammalian vertebrate, the medaka fish.
AB  - Until the onset of anaphase, sister chromatids are bound to each other by a multi
      subunit protein complex called cohesin. Since chromosomes in meiosis behave
      differently from those in mitosis, the cohesion and separation of homologous
      chromosomes and sister chromatids in meiosis are thought to be regulated by
      meiosis-specific cohesin subunits. Actually, several meiosis-specific cohesin
      subunits, including Rec8, STAG3 and SMC1beta, are known to exist in mammals;
      however, there are no reports of meiosis-specific cohesin subunits in other
      vertebrates. To investigate the protein expression and localization of cohesin
      subunits during meiosis in non-mammalian species, we isolated cDNA clones
      encoding SMC1alpha, SMC1beta, SMC3 and Rad21 in the medaka and produced
      antibodies against recombinant proteins. Medaka SMC1beta was expressed solely in
      gonads, while SMC1alpha, SMC3 and Rad21 were also expressed in other organs and
      in cultured cells. SMC1beta forms a complex with SMC3 but not with Rad21, in
      contrast to SMC1alpha, which forms complexes with both SMC3 and Rad21. SMC1alpha
      and Rad21 were mainly expressed in mitotically dividing cells in the testis
      (somatic cells and spermatogonia), although their weak expression was detected in
      pre-leptotene spermatocytes. SMC1beta was expressed in spermatogonia and
      spermatocytes. SMC1beta was localized along the chromosomal arms as well as on
      the centromeres in meiotic prophase I, and its existence on the chromosomes
      persisted up to metaphase II, a situation different from that reported in the
      mouse, in which SMC1beta is lost from the chromosome arms in late pachytene
      despite its universal presence in vertebrates.

PMID- 15261827
TI  - Overlapping and distinct expression domains of Zic2 and Zic3 during mouse
      gastrulation.
AB  - The Zic genes are the vertebrate homologues of the Drosophila Odd-paired gene.
      Mutations in two of these genes are associated with human congenital genetic
      disorders. Mutation of human and mouse Zic2 is associated with holoprosencephaly
      which is caused by a defect of ventral forebrain development and mutation of
      human and mouse Zic3 is associated with a X-linked heterotaxy syndrome that
      results from a failure of left-right axis formation. The embryological role of
      the Zic genes in these disorders is not well understood. Here we show that both
      of these genes are expressed prior to and throughout gastrulation. The genes show
      some broad similarities in their expression domains. Both genes however are also
      uniquely expressed in some tissues and these unique domains correlate with
      regions that potentially play a role in the aetiology of the respective genetic
      disorders. During primitive streak stages Zic2 is expressed transiently and
      uniquely in the node and the head process mesendoderm. The head process is known
      to be required for the establishment or maintenance of the ventral forebrain,
      which is the region disrupted in holoprosencephaly. Zic3 is not expressed in the
      node during primitive streak stages but is expressed in and around the node
      beginning from the head fold stages of development. This expression of Zic3
      correlates well with the first steps in the establishment of the left-right axis.
      We also examined the expression of the closely related gene, Zic1, and did not
      detect any transcripts in gastrulation stage embryos.

PMID- 15261828
TI  - Identification of unique, differentiation stage-specific patterns of expression
      of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse
      testis.
AB  - The bromodomain, an evolutionarily conserved motif that binds acetyl-lysine on
      histones, is found in many chromatin-associated proteins, transcription factors,
      and in nearly all known histone acetyltransferases. The BET subclass of
      bromodomain-containing proteins contains two bromodomains and one ET domain and
      consists of at least four members in mouse and human, Brd2, Brd3, Brd4, and Brdt.
      We isolated mouse cDNAs for these genes and studied their expression patterns
      with particular focus on the testis. Northern hybridization revealed that Brd3 is
      most abundant in testis, ovary, placenta, uterus, and brain; that Brd4 is rather
      ubiquitously expressed but is most abundant in mid-gestation embryo, testis,
      ovary, and brain; and that Brdt is specifically expressed in testis. In situ
      hybridization and immunostaining on histological sections of mouse testes
      revealed a strikingly specific and dynamic change of cellular specificity in the
      germ line during the progression of spermatogenesis. Brd4 is expressed in
      spermatogonia, Brdt is only expressed in mid- to late-spermatocytes, Brd2 is
      expressed in diplotene spermatocytes and round spermatids and at low levels in
      spermatogonia, and Brd3 is expressed in round spermatids. This unique expression
      pattern suggests that genes in this subclass are not simply redundant. Rather,
      their expression is tightly regulated in the male germ cell lineage, suggesting
      that they likely have specific roles in different developmental stages and/or
      cell types.

PMID- 15261829
TI  - Lhx2 is expressed in the septum transversum mesenchyme that becomes an integral
      part of the liver and the formation of these cells is independent of functional
      Lhx2.
AB  - Liver development is based on reciprocal interactions between ventral foregut
      endoderm and adjacent mesenchymal tissues. Targeted disruption of the LIM
      homeobox gene Lhx2 has revealed that it is important for the expansion of the
      liver during embryonic development, whereas it appears not to be involved in the
      induction of hepatic fate. It is not known whether Lhx2 is expressed in the
      endodermal or mesenchymal portion of the liver, or if the cells normally
      expressing Lhx2 are absent or present in the liver of Lhx2(-/-) embryos. To
      address this we have analyzed gene expression from the Lhx2 locus during hepatic
      development in wild type and Lhx2(-/-) mice. Lhx2 is expressed in cells of the
      septum transversum mesenchyme adjacent to the liver bud from embryonic day 9. The
      hepatic cords subsequently migrate into and intermingle with the Lhx2+ cells of
      the septum transversum mesenchyme. Lhx2 expression is thereafter maintained in a
      subpopulation of mesenchymal cells in the liver until adult life. In adult liver
      the Lhx2+ mesenchymal cells co-express desmin, a marker associated with stellate
      cells. At embryonic day 10.5, cells expressing the mutant Lhx2 allel are present
      in Lhx2(-/-) livers, and expression of Hlx, hepatocyte growth factor, Hex and
      Prox1, genes known to be important in liver development, is independent of
      functional Lhx2 expression. Thus, Lhx2 is specifically expressed in the liver
      associated septum transversum mesenchyme that subsequently becomes an integral
      part of the liver and the formation of these mesenchymal cells does not require
      functional Lhx2.

PMID- 15261830
TI  - Cloning and expression of mars, a novel member of the guanylate kinase associated
      protein family in Drosophila.
AB  - The Membrane-Associated Guanylate Kinase (MAGUK) family of anchor proteins are
      involved in organising a range of molecules such as cell adhesion molecules,
      receptors, and intracellular signalling molecules at cell junctions. In mammals,
      the PSD-95/SAP-90/hDlg class of MAGUK proteins bind to a family of Guanylate
      Kinase Associated Proteins (GKAPs) that have been found at presumptive synaptic
      sites in neurons. Here we describe the identification of Mars, a novel Drosophila
      protein belonging to the GKAP family. RT-PCR analysis reveals that Drosophila
      mars mRNA and protein are predominantly expressed in embryos and in the adult
      germline. In embryos, mars is expressed in central nervous system and brain, as
      determined by RNA in situ hybridisation. In testes, mars is strongly expressed in
      pre-meiotic germ cells, but is not found in somatic or post-meiotic cells,
      indicating that in addition to their role in neuronal cells, GKAP proteins are
      also likely to play a role in germline development.

PMID- 15261831
TI  - Expression patterns of the coe/ebf transcription factor genes during chicken and
      mouse limb development.
AB  - The COE (Collier/Olf/EBF) family of transcription factors comprises a single
      member in Drosophila and four members in human and mice. We have examined by in
      situ hybridization the expression patterns of each ebf/coe gene during limb
      development in mouse and chicken embryos. Expression of mouse ebf1, 2 and 3 is
      detected in mesenchymal cells from stages E10.5-11, expression of ebf2 being
      restricted to the presumptive zeugopod. Cross sections of mouse and chicken limb
      buds at several stages reveal that ebfs are specifically expressed in the
      connective tissues surrounding chondrogenic condensations and forming tendons.
      They thus represent useful new markers for studying vertebrate limb development,
      particularly formation of ligaments.

PMID- 15261832
TI  - Expression of olfactory receptors in the cribriform mesenchyme during prenatal
      development.
AB  - Olfactory receptors (ORs) are expressed in sensory neurons of the nasal
      epithelium, where they are supposed to be involved in the recognition of suitable
      odorous compounds and in the guidance of outgrowing axons towards the appropriate
      glomeruli in the olfactory bulb. During development, some olfactory receptor
      subtypes have also been found in non-sensory tissues, including the cribriform
      mesenchyme between the prospective olfactory epithelium and the developing
      telencephalon, but it is elusive if this is a typical phenomenon for ORs.
      Monitoring the onset and time course of expression for several receptor subtypes
      revealed that 'extraepithelial' expression of ORs occurs very early and
      transiently, in particular between embryonic stages E10.25 and E14.0. In later
      stages, a progressive loss of receptor expressing cells was observed. Molecular
      phenotyping demonstrated that the receptor expressing cells in the cribriform
      mesenchyme co-express key elements, including Galpha(olf), ACIII and OMP,
      characteristic for olfactory neurons in the nasal epithelium. Studies on
      transgenic OMP/GFP-mice showed that 'extraepithelial' OMP/GFP-positive cells are
      located in close vicinity to axon bundles projecting from the nasal epithelium to
      the presumptive olfactory bulb. Moreover, these cells are primarily located where
      axons fasciculate and change direction towards the anterior part of the
      forebrain.

PMID- 15261833
TI  - her7 and hey1, but not lunatic fringe show dynamic expression during
      somitogenesis in medaka (Oryzias latipes).
AB  - Epithelialized somites form repeatedly from the unsegmented presomitic mesoderm
      (PSM) in the tailbud of vertebrate embryos. Mutant analysis has shown that the
      Delta-Notch pathway is essential for the temporal and spatial control of somite
      formation. Several components of this pathway show cyclic transcription, which is
      driven by a molecular oscillator. This oscillator is thought to act similarly in
      different vertebrates. In this study, we used the Japanese Medaka (Oryzias
      latipes) to examine the expression of three factors of the Delta-Notch cascade
      that are known to show cyclic expression in the PSM of higher vertebrates. We
      report that in contrast to the situation in mice, lunatic fringe (lfng) in medaka
      is expressed in a non-dynamic fashion in the rostral halves of the formed somites
      and the anteriormost PSM. On the other hand, her7, a member of the hairy/Enhancer
      of-split related (Her) gene family, shows cyclic expression in the medaka PSM.
      Although this is similar in zebrafish, there are important differences in the
      distribution of transcripts in the PSM indicating different modes of regulation
      in both fish species. Finally, we show that hey1, another Delta-Notch regulated
      bHLH gene, is dynamically expressed in the PSM of medaka, similar to hey1 in
      zebrafish and the hey2 orthologs in mice and chicken. Interestingly, medaka hey1
      is also expressed in the dorsal aorta and the heart, two tissues where hey2, but
      not hey1, is expressed in zebrafish. This shows that several components of the
      Delta-Notch pathway are differently regulated during somitogenesis in different
      species.

PMID- 15261834
TI  - Expression patterns of three estrogen receptor genes during zebrafish (Danio
      rerio) development: evidence for high expression in neuromasts.
AB  - The estrogen receptor (ER) genes encode a group of nuclear enhancer proteins,
      which are important ligand-activated transcription factors, modulating estrogen
      target gene transcription. In this study we analyzed expression patterns of three
      zebrafish ER genes, esr1, esr2a, and esr2b, during development using whole-mount
      in situ hybridization. High levels of esr2a and esr2b of maternal origin are
      inherited and segregated to the blastomers. After the mid-blastula transition,
      the three genes exhibit similar spatio-temporal patterns of expression. In 24 h
      postfertilization (hpf) embryos, high levels of esr2a and esr2b and low levels of
      esr1 mRNAs are detected in the epidermis, pectoral fin buds, hatching gland and,
      to a lesser extent, developing brain. From 24 hpf onward, the expression of the
      three genes is down-regulated in the epidermis. By 60 hpf, esr2a mRNA is abundant
      in mature primary neuromasts of the anterior line system and by 3 days
      postfertilization (dpf), all mature primary neuromasts in both the anterior and
      posterior lateral line systems express significant levels of esr2a and esr2b
      transcripts. Histological sections show a high level of esr2a transcripts in both
      mechanoreceptive hair cells and supporting cells. The transcripts are still
      detected after neomycin-induced hair cell death, consistent with the presence of
      esr2a transcripts in supporting cells. From 6 dpf onward, esr2a and esr2b
      transcripts are robustly co-expressed in primary neuromasts, branchial arches,
      pectoral fins, and anal papilla, while slight labeling is observed for esr1
      transcripts.

PMID- 15261835
TI  - The mouse frizzled 8 receptor is expressed in anterior organizer tissues.
AB  - Wnt signaling has been shown to be important for axis formation in vertebrates.
      However, no Wnt ligand or receptor has been shown to be specifically expressed in
      all the organizer tissues in the mouse embryo. Here we report that the mouse
      frizzled 8 (mfz8) gene, a Wnt receptor, is expressed in the anterior visceral
      endoderm (AVE) and the anterior primitive streak, which have been shown to
      possess organizer activity. mFz8 is also expressed in the descendents of the
      anterior streak that comprise the anterior mesendoderm (AME) at midgastrulation,
      with subsequent expression in the anterior neurectoderm, which is specified and
      patterned by the AVE and AME. Thus, mfz8 is specifically expressed in the
      organizer tissues that establish the anterior-posterior axis in the mouse embryo.

PMID- 15261836
TI  - Duplicate zebrafish runx2 orthologues are expressed in developing skeletal
      elements.
AB  - The differentiation of cells in the vertebrate skeleton is controlled by a
      precise genetic program. One crucial regulatory gene in the pathway encodes the
      transcription factor Runx2, which in mouse is required for differentiation of all
      osteoblasts and the proper development of a subset of hypertrophic chondrocytes.
      To explore the differentiation of skeletogenic cells in the model organism
      zebrafish (Danio rerio), we have identified two orthologues of the mammalian
      gene, runx2a and runx2b. Both genes share sequence homology and gene structure
      with the mammalian genes, and map to regions of the zebrafish genome displaying
      conserved synteny with the region where the human gene is localized. While both
      genes are expressed in developing skeletal elements, they show evidence of
      partial divergence in expression pattern, possibly explaining why both
      orthologues have been retained through teleost evolution.

PMID- 15261837
TI  - Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse
      development.
AB  - Dystrobrevins are a family of dystrophin-related and dystrophin-associated
      proteins. alpha-dystrobrevin-1 knockout mice suffer from skeletal and cardiac
      myopathies. It has been suggested that the pathology is caused by the loss of
      signalling functions but the exact role of dystrobrevins is largely unknown. We
      have analysed the spatial and temporal expression of alpha-dystrobrevin-1 during
      mouse embryogenesis and found striking developmental regulation and distribution
      patterns. During development this protein was expressed not only in muscle but
      also in the CNS, sensory organs, epithelia and skeleton. Particularly interesting
      was the correlation of alpha-dystrobrevin-1 expression with the induction of
      various differentiation processes in the developing eye, inner ear, pituitary,
      blood-brain barrier, stomach epithelium and areas of the brain, dorsal root
      ganglia and spinal cord. In contrast, this specific expression at the induction
      phase decreased/disappeared at later stages of development.

PMID- 15261838
TI  - Bono1: a gene associated with regions of deposition of bone and dentine.
AB  - We have examined the mRNA expression pattern of the murine expressed sequence tag
      (EST) clone in embryonic and early postnatal mice. Expression was strongly and
      specifically localised to developing bones and odontoblasts in teeth, therefore
      we have named this gene Bono1 (Bone and odontoblasts). Bono1, which has human,
      rat and chicken orthologues designated as FKSG28 was expressed in most
      ossification regions of the head including calvarial bones, skull and jaws.
      Expression was localised to osteoblasts derived from both intramembraneous and
      endochondral ossification processes. Comparative analysis of the expression of
      Bono1 in the mandible with Bone sialoprotein (BSP), a marker of advanced
      osteoblastogenesis, revealed that Bono1 expression starts later in the osteoblast
      cell lineage than BSP. In the tooth, Bono1 was localised in secretory
      odontoblasts. This expression was complementary to BSP, which was only present in
      early pre-odontoblasts. In secretory odontoblasts, Bono1 was shown to be co
      expressed with Dentin sialophosphoprotein (DSPP). In summary, Bono1 was expressed
      in functional osteoblasts and odontoblasts and was associated with regions of
      matrix mineralization.

PMID- 15261839
TI  - Characterization of Xenopus Phox2a and Phox2b defines expression domains within
      the embryonic nervous system and early heart field.
AB  - The closely related homeodomain containing genes, Phox2a and Phox2b, are
      essential for neuronal specification and differentiation within discrete subsets
      of neurons during vertebrate embryogenesis. We have isolated Xenopus Phox2
      homologs, termed Xphox2a and Xphox2b, and characterized their expression during
      early development. In addition, we have characterized a Phox2a splice variant,
      termed Xphox2a.2, which lacks homeo- and C-terminal protein coding domains.
      Xphox2a, Xphox2a.2 and Xphox2b transcripts are expressed in dynamic temporal and
      regional patterns during nervous system development. The expression of Xphox2a
      and Xphox2b is only partially overlapping and includes cranial motor and
      interneuron populations as well as peripheral sympathetic and cranial ganglion
      neurons, sites linked to Phox2 expression in other species. In addition, we have
      identified an early domain of Xphox2a and subsequent Xphox2b expression in
      ventral regions of the embryo, within the developing heart field. XPhox2
      expression within this domain is preceded by the gastrula-stage expression of the
      proneural basic helix-loop-helix transcription factor, Xash1, pointing to a new
      region of action for this group transcription factors during vertebrate
      development.

PMID- 15261840
TI  - Hormone replacement therapy: controversies, pros and cons.
AB  - Hormone replacement therapy (HRT) is a complicated clinical issue that requires
      an in-depth risk/benefit assessment. The term HRT includes both oestrogen plus
      progestin therapy (OPT) and oestrogen-only therapy (OT). Much research has been
      done with the former, but additional research is still needed for the latter.
      This chapter aims to provide a comprehensive overview of the key risks and
      benefits in order to assist clinicians and patients confronting this issue. In
      approaching the vast amount of data on HRT a caveat is in order: many of the
      issues involved are not black and white. The clinical data are often conflicting
      and careful analysis is required. Despite the discrepancies between the various
      HRT studies, there is much to be gleaned from a close examination of the data.
      The primary risks associated with HRT use are related to breast cancer and
      cardiovascular health. Recent clinical trial data have pointed to a slight
      increase in the number of breast cancers among women using HRT compared to
      placebo. With regard to cardiovascular health, the data have shown an increase in
      stroke and (VTE) but there is also evidence of a possible cardioprotective
      effect. The major benefits include relief of menopausal symptoms (including
      vasomotor instability, sexual dysfunction, mood, fatigue and skin issues) and a
      decrease in fracture risk.

PMID- 15261841
TI  - Growth hormone secretagogues: prospects and potential pitfalls.
AB  - The growth hormone secretagogues (GHSs) are the first well-characterised agents
      that rejuvenate the growth hormone (GH)/insulin-like growth factor (IGF-1) axis.
      This property was discovered during investigations of the underlying causative
      mechanisms of age-related endocrine changes. Chronic administration of the long
      acting GHS, MK-0677, reverses the age-related decline in pulse-amplitude of GH
      secretion and restores IGF-1 levels producing profiles typical of young adults.
      This restoration is accompanied by improvements in body composition in frail
      elderly subjects. When given acutely, the GHSs also increase appetite. Following
      cloning and characterisation of the GHS-receptor (GHS-R) an endogenous ligand,
      ghrelin, was isolated and identified. Ghrelin shares the GH releasing and
      orexigenic properties of the GHSs. Studies using Ghsr-null mice confirmed that
      the GHS-R was the ghrelin-receptor; hence, the GHSs should be considered to be
      'ghrelin mimetics.' Ghrelin levels are reported to decline during ageing,
      therefore long-acting GHSs are ideal candidates for ghrelin replacement therapy.

PMID- 15261842
TI  - Androgens and the ageing male.
AB  - Serum testosterone levels peak in early adulthood in men and fall progressively
      with age. Since sex hormone binding globulin increases with age, the unbound
      forms of testosterone (free and bioavailable testosterone) fall more steeply than
      total testosterone levels. Serum testosterone levels below the normal range for
      young healthy adult males provide chemical evidence of androgen deficiency
      independent of the age of the patient. When accompanied by signs or symptoms that
      are compatible with androgen deficiency, treatment with testosterone should be
      considered in older men without evidence of prostate or breast cancer. While such
      therapy for younger hypogonadal men has shown benefit on libido, mood, muscle
      mass, muscle strength, bone mineral density and haematocrit, similar benefits in
      older men have not been as adequately assessed. While there is no convincing
      evidence that testosterone treatment in older men will increase the risk of
      cardiovascular or prostate cancer, long-term, well-controlled studies are lacking
      and needed. Treatment options for older men include injectable, transdermal and
      transbuccal testosterone preparations.

PMID- 15261843
TI  - Dehydroepiandrosterone and ageing.
AB  - Dehydroepiandrosterone (DHEA) is the major steroid produced by the adrenal zona
      reticularis and, in contrast to cortisol and aldosterone, its secretion declines
      with ageing. This has generated major interest in its putative role as an 'anti
      ageing' hormone. However, it is not clear that the age-associated, physiological
      decline in DHEA secretion represents a harmful deficiency. DHEA exhibits its
      action mainly by conversion to sex steroids. In addition, DHEA has neurosteroidal
      properties and may exhibit direct action via specific binding sites on
      endothelial cells. There is convincing evidence for beneficial effects of DHEA in
      patients with adrenal insufficiency and future research will hopefully elucidate
      its role in patients receiving pharmacological glucocorticoid treatment. However,
      in healthy elderly subjects, current evidence from randomised, controlled trials
      does not justify the use of DHEA, with no major beneficial effects reported and,
      in addition, potentially adverse effects on sex steroid-dependent tumour growth
      need to be considered.

PMID- 15261844
TI  - Life extension versus improving quality of life.
AB  - There are two principal directions in ageing research: (i) the quest for
      understanding the mechanisms that determine the length of life and the use of
      such knowledge in order to find a potentially life extending treatment and (ii)
      the attempt to improve the quality of life in the elderly by reversing or
      preventing functional decline of different tissues without primarily extending
      life span. This chapter addresses the importance of assessing the potential
      impact of interventions on quality of life rather than extending life.

PMID- 15261845
TI  - The role of insulin and insulin-like growth factor-I in mammalian ageing.
AB  - Research with invertebrates over the past 10 years has suggested that alterations
      in insulin and/or insulin-like growth factor I (IGF-I) signalling result in
      increased lifespan and retard ageing. In this chapter, we describe the current
      research in mammalian systems with respect to the role of insulin or IGF-I in
      ageing. Using rodent models of caloric restriction and genetic mouse models, e.g.
      the Ames and Snell dwarf mice, fat-specific insulin receptor knockout mice
      (FIRKO) and mice that are heterozygous for the IGF-I receptor (Igf1r+/-),
      investigators have shown that a reduction in plasma levels of insulin and/or IGF
      I or reductions in insulin/IGF-I signalling appear to be correlated with
      increased longevity and retarded ageing.

PMID- 15261846
TI  - Pitfalls of animal model systems in ageing research.
AB  - Often, reports of anti-ageing research using animal models are overly optimistic
      and incomplete. Without having the details of the study (issues inherent with the
      animal models, the condition of the animal colony, the replicability of the
      findings, for example), even the educated public can find it difficult to
      interpret the reports accurately. This chapter provides background information
      about ageing research and animal models in general and arms readers with
      guidelines they can use to assist them when analyzing reports of ageing research
      using those models. The article also uses the guidelines to briefly evaluate
      three anti-ageing treatment candidates: one in the very early stages of testing
      (resveratrol), one that has been proven unfounded as an anti-ageing intervention
      by testing [dehydroepiandrosterone (DHEA)] and one that has undergone testing
      successfully (l-deprenyl).

PMID- 15261847
TI  - Insulin-like growth factor I and bone mineral density: experience from animal
      models and human observational studies.
AB  - The insulin-like growth factor (IGF) system has been linked to the process of
      bone acquisition through epidemiological analyses of large cohorts and in vitro
      studies of bone cells. However, the precise relationship between the expression
      of IGF-I in bone and skeletal homeostasis or pathological conditions such as
      osteoporosis, remains poorly defined. Recent advances in genomic engineering have
      resulted in the development of better in vivo models for testing the role of IGF
      I during development and the maintenance of the adult skeleton. Evidence from
      conditional mutagenesis studies of IGF-I has opened up a new area of in vivo
      analysis. These studies suggest that serum IGF-I levels may represent more than a
      storage depot or permissive factor during skeletal acquisition and that tissue
      IGF-I is essential for normal bone formation. The implications from these animal
      models are far-reaching and suggest that newer approaches for manipulating the
      IGF regulatory system may one day be useful as therapeutic adjuncts for the
      treatment of osteoporosis.

PMID- 15261848
TI  - Endocrinology of anorexia of ageing.
AB  - Appetite and food intake decrease with normal ageing, predisposing to the
      development of under-nutrition. Under-nutrition is common in older people and has
      been implicated in the development and progression of chronic diseases commonly
      affecting the elderly, as well as in increasing mortality. An understanding of
      the factors that contribute to the physiological and pathological declines in
      food intake in older people is likely to aid in the development of effective
      forms of prevention and treatment. Ageing affects many of the endocrine factors
      involved in the control of appetite and feeding but few studies have been
      performed in humans to clarify these changes. Possible hormonal causes of the
      anorexia of ageing include increased activity of cholecystokinin, leptin and
      various cytokines and reduced activity of ghrelin and testosterone.

PMID- 15261850
TI  - TMS and drugs.
AB  - The application of a single dose of a CNS active drug with a well-defined mode of
      action on a neurotransmitter or neuromodulator system may be used for testing
      pharmaco-physiological properties of transcranial magnetic stimulation (TMS)
      measures of cortical excitability. Conversely, a physiologically well-defined
      single TMS measure of cortical excitability may be used as a biological marker of
      acute drug effects at the systems level of the cerebral cortex. An array of
      defined TMS measures may be used to study the pattern of effects of a drug with
      unknown or multiple modes of action. Acute drug effects may be rather different
      from chronic drug effects. These differences can also be studied by TMS measures.
      Finally, TMS or repetitive TMS by themselves may induce changes in endogenous
      neurotransmitters or neuromodulators. All these possible interactions are the
      focus of this in-depth review on TMS and drugs.

PMID- 15261851
TI  - Should transcranial magnetic stimulation research in children be considered
      minimal risk?
AB  - OBJECTIVE: Transcranial magnetic stimulation (TMS) is a neurophysiologic
      technique with research applications. Institutional Review Boards (IRBs) must
      carefully consider potential risks and possible benefits in research involving
      children. The purpose of this study is to provide concise information for
      investigators and IRBs about the safety of single and paired pulse TMS research
      in children. METHODS: This paper has 4 sections: (I) Regulations governing
      research in children are reviewed and applied to the use of TMS. (II) Energy
      imparted by TMS is assessed in terms of theoretical biological risks to human
      subjects. (III) Through MEDLINE review, the empirical evidence of risk from TMS
      is assessed. Reported adverse events, including issues related to risk of
      seizures and of hearing loss, are summarized. (IV) Safety data are presented from
      a study of TMS in children with Tourette Syndrome. RESULTS: No published or
      empirical evidence was found to suggest that single or paired pulse TMS is
      associated with more than minimal risk in children. CONCLUSIONS: IRBs may
      consider well-designed studies using single and paired pulse TMS protocols
      similar to those described in this study as bearing minimal risk to children.
      SIGNIFICANCE: This manuscript may be useful as a reference to IRBs and TMS
      investigators.

PMID- 15261852
TI  - Intra-subject reliability of parameters contributing to maps generated by
      transcranial magnetic stimulation in able-bodied adults.
AB  - OBJECTIVE: This study evaluated the reliability of several parameters
      contributing to topographic motor cortical maps of the extensor digitorum
      communis (EDC) within able-bodied participants, across 3 sessions and from both
      hemispheres with greater precision than previously reported. METHODS: Nine
      healthy right-handed males aged 44-75 years were studied at 3 separate sessions,
      spaced 7-14 days apart. Transcranial magnetic stimulation (TMS) was used to
      elicit motor evoked potentials (MEP) in the contralateral EDC. Closely spaced
      surface electrodes were used to record the MEPs. RESULTS: TMS-related parameters
      did not demonstrate a significant difference within participants across sessions
      and between hemispheres, with the exception of the hotspot distance, center of
      gravity distance, and normalized map volume. Hotspot and COG distances were
      determined from the Euclidean equation to calculate the distance in x,y
      coordinates traveled over sessions: one to two (distance A) and two to three
      (distance B). The hotspot distance, center of gravity distance and normalized map
      volume demonstrated a significant difference between right and left hemispheres,
      within participants. Adjusting for time and examining mean changes for
      hemispheres across sessions revealed that there was a 9-fold greater movement
      over sessions in the left hemisphere among these variables. CONCLUSIONS: TMS
      related parameters are reliable within participants across 3 sessions. These data
      should be useful for planning and interpreting TMS studies using a healthy or
      patient population before and after an intervention.

PMID- 15261853
TI  - EMG for assessing the recovery of voluntary movement after acute spinal cord
      injury in man.
AB  - OBJECTIVE: Multi-channel electromyogram (EMG) was used to examine the pattern and
      time-course of voluntary contraction recovery in subjects with acute traumatic
      spinal cord injury (SCI), concentrating on the latest time after injury at which
      a given muscle would begin to show voluntary recruitment. METHODS: We conducted
      repeated measures of voluntary contractions of 12 lower limb muscles (for all
      subjects) and 12 upper-limb muscles (for subjects with cervical injury),
      beginning within days of the injury and extending for 1 or more years post
      injury. The EMG interference pattern was scored in a blinded fashion from tape
      records. RESULTS: We recruited 229 subjects, including 152 from whom repeated
      measures were made. Several different patterns of recovery were identified. For
      persons with motor-incomplete injury to the cervical or thoracic spine, EMG
      recruitment had not yet occurred by 5 weeks post-injury in roughly 1/2 of all
      lower limb muscles, and prolonged delays between injury and recruitment onset
      were sometimes seen. Injury to the thoracolumbar spine was frequently associated
      with very long delays (i.e. >1 year) between injury and resumption of volitional
      contraction of distal lower limb muscles. DISCUSSION: The incidence of
      neurologically incomplete SCI is rising. In such subjects, delays of 1 or more
      months between injury and the onset of voluntary contraction are common for
      muscles of the distal upper limbs (for cervical injury) and lower limbs. Given
      the abbreviated period of in-patient rehabilitation now routine in the United
      States, these subjects in particular will benefit from frequent follow-up
      evaluations to assess spontaneous recovery and design appropriate rehabilitation
      strategies to maximize functional independence. Moreover, the potential for
      delayed recovery must be considered when designing and implementing novel
      clinical interventions for treating SCI, to better differentiate between
      spontaneous and treatment-related improvements in neurologic function.

PMID- 15261854
TI  - Primary motor cortex activation during action observation revealed by wavelet
      analysis of the EEG.
AB  - OBJECTIVE: We characterised the spectral response of the EEG to median nerve
      stimulation using wavelet analysis, and compared the relative magnitudes of
      effect of several different action-observation conditions on the beta and mu
      'rebound' rhythms. METHODS: EEG responses to median nerve stimulation were
      recorded from 8 normal adult subjects during baseline or action-observation
      conditions. Analysis was performed by convolution of the EEG with a family of
      wavelets. RESULTS: Decreased power in the mu and beta bands characterized the EEG
      following median nerve stimulation until 500 ms post-stimulus, followed by
      increased amplitudes ('rebound') of both rhythms. Execution of movement,
      observation of object-directed movement and observation of somatosensory
      stimulation all caused a decreased rebound of the beta rhythm whereas observation
      of aimless thumb movement did not. CONCLUSIONS: Wavelet analysis of the EEG
      extracted similar features reported in previous studies using bandpass filtering
      with respect to the activation state of the motor cortex during action
      observation. Further, our results show that observation of somatosensory
      stimulation alone is sufficient to cause significant modulation of motor cortex
      activity. SIGNIFICANCE: These results add further details as to what stimuli can
      activate the human mirror neuron system and the analytical techniques used may be
      useful for future studies of clinical populations such as autistic patients.

PMID- 15261855
TI  - Experimental muscle pain increases trapezius muscle activity during sustained
      isometric contractions of arm muscles.
AB  - OBJECTIVE: In the present study, the influence of experimental muscle pain on
      muscle co-ordination and fatigue development during sustained isometric elbow
      flexion was investigated. METHODS: Conventional surface electromyography (EMG)
      was recorded from the biceps brachii, brachioradialis, deltoideus and trapezius
      muscle during isometric elbow flexion at 40% maximum force. Single motor unit
      (MU) conduction velocity in the biceps brachii was assessed using a high spatial
      resolution surface EMG technique. Measurements were performed on 15 healthy
      subjects before, during and after (1) injection of hypertonic (pain condition)
      and (2) isotonic saline (control) into the biceps brachii. The pain intensity was
      assessed on a 10 cm visual analogue scale. RESULTS: The experimental results
      showed in both experimental sessions a fatigue-related increase of the root mean
      square value of EMG (222+/-164% of the baseline), and a decrease of the median
      frequency (118+/-16% of the baseline) in all investigated muscles. A maximum pain
      level of in average 3.2 cm on the visual analogue scale was reached after
      injection of hypertonic saline during contraction. Differences between painful
      and control condition were seen in an increased trapezius activity (230+/-141%)
      during pain. The global EMG activity of the brachioradialis and biceps brachii
      was unaffected by experimental muscle pain in line with unaffected single MU
      conduction velocity in the biceps brachii. Differences in endurance time (mean
      89.3 and 102.3 s, pain and control, respectively) were not significant.
      CONCLUSIONS/SIGNIFICANCE: The findings suggest that upper extremity pain could be
      a possible source for overloading the trapezius muscle and as such is an
      important factor in occupational settings.

PMID- 15261856
TI  - Influences of chemically-induced muscle pain on power output of ballistic upper
      limb movements.
AB  - OBJECTIVE: To analyse the conditioning effects of localised acute muscle pain on
      power output during ipsi- and contra-lateral ballistic arm extensions. METHODS:
      Eight male subjects performed right arm (ipsilateral) and left arm (contra
      lateral) bench press movements. The power output (and force and velocity) of the
      concentric phase of movement was measured before and during muscle pain induced
      by a standardised intramuscular injection of levo-ascorbic acid in the right
      pectoralis major muscle (prime mover muscle) and in the lateral head of the right
      triceps brachii muscle (synergist). RESULTS: The power output of ipsi- and contra
      lateral arm bench press movements was significantly decreased during pain of the
      right pectoralis major muscle, but not during pain of the right lateral triceps
      muscle. The velocity and force were both affected and contributed to the decrease
      in power output. CONCLUSIONS: Acute muscle pain of a prime mover muscle reduces
      ipsi- and contra-lateral motor performance of ballistic upper limb extension.
      This is not a generalised or non-specific inhibitory effect on the motor system,
      since pain failed to modify motor performance when applied to a synergist, non
      prime mover, muscle. A basically bilateral executive cortical plan for ballistic
      upper limb extension could explain the conditioning effect of muscle pain on both
      ipsi- and contra-lateral arm. SIGNIFICANCE: The results presented here
      contributes to the understanding of the conditioning effects of muscle pain on
      movement performance.

PMID- 15261857
TI  - Patterns of abnormal motor cortex excitability in atypical parkinsonian
      syndromes.
AB  - OBJECTIVE: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP),
      and corticobasal-ganglionic degeneration (CBGD) are all clinically characterized
      by an akinetic-rigid syndrome together with a variety of additional signs. We
      hypothesised that these atypical parkinsonian syndromes (APS) will show
      distinctive patterns in their motor output upon transcranial magnetic stimulation
      (TMS) due to their different underlying anatomico-functional deficits. METHODS:
      We performed single and paired-pulse TMS and assessed inhibitory and excitatory
      response parameters from the first dorsal interosseus muscles in 13 patients with
      MSA, 18 with PSP, 13 with CBGD, 15 patients with Parkinson's disease and 17
      healthy subjects. RESULTS: PSP and MSA patients had significantly enlarged
      response amplitudes at rest, reduced intracortical inhibition (ICI) and prolonged
      ipsi- and contralateral silent periods, whereas CBGD patients showed
      significantly increased motor thresholds, smaller response amplitudes at rest,
      shortened contralateral silent period, reduced transcallosal inhibition and a
      reduced ICI. In 22% of APS patients ipsilateral motor responses occurred in upper
      limb muscles irrespective of the underlying disease. CONCLUSIONS: Our results
      indicate that motor cortex disinhibition is predominant in patients with PSP and
      MSA. In CBGD more severe neuronal cell loss in the motor cortex itself may lead
      to hypoexcitability of corticospinal and transcallosal pathways.

PMID- 15261858
TI  - Galvanic evoked vestibulospinal and vestibulocollic reflexes in stroke.
AB  - OBJECTIVE: Following stroke, the startle reflex, mediated via the reticulospinal
      tract, is often facilitated. Vestibulospinal reflexes are another bulbospinal
      reflex, abnormalities of which may contribute to impaired body posture and stance
      following stroke. We recorded galvanic evoked vestibulospinal and vestibulocollic
      reflexes to assess whether these showed similar changes to those for startle
      following stroke affecting the pons and above. METHODS: Twenty-four stroke
      subjects (aged 40-82) were studied in the vestibulospinal part of the study, 21
      stroke subjects (aged 40-81 years) were studied in the vestibulocollic part,
      including 18 studied in both. Transmastoid galvanic (DC) current was used to
      stimulate the vestibular nerve. Vestibulocollic responses were recorded from the
      sternocleidomastoid muscles and vestibulospinal responses from over soleus in
      standing subjects. RESULTS: Vestibulocollic reflex amplitudes and latencies
      showed no significant differences between the two sides. Similarly short latency
      (SL) and medium latency (ML) vestibulospinal reflexes did not differ
      significantly in frequency, latency or amplitude between the affected and
      unaffected legs. CONCLUSIONS: Vestibular reflexes are not facilitated by stroke
      at or above the pontine level. The exaggeration of startle by stroke may be
      specific to this reflex.

PMID- 15261859
TI  - Cognitive tasks augment gamma EEG power.
AB  - OBJECTIVE: Gamma EEG oscillations are low amplitude rhythms in the 30-100 Hz
      range that correlate with cognitive task execution. They are usually reported
      using time-locked averaging of EEG during repetitive tasks. We tested the
      hypothesis that continuous gamma EEG would be measurable during mental tasks.
      METHODS: We investigated sustained human gamma EEG oscillations induced by 8
      cognitive tasks (Visual Checkerboard, Expectancy, Reading, Subtraction, Music,
      Expectancy, Word learning, Word recall, and a Video Segment) in 20 subjects using
      standard digital EEG recording and power spectral analysis. RESULTS: All of the
      cognitive tasks augmented gamma power relative to a control condition (eyes open
      watching a blank computer screen). This enhancement was statistically significant
      at more than one scalp site for all tasks except checkerboard. The Expectancy,
      Learning, Reading and Subtraction tasks expressed the most impressive gamma
      response, up to 5 fold above the control condition and there was some task
      related specificity of the distribution of increased gamma power, especially in
      posterior cortex with visual tasks. CONCLUSIONS: Widespread gamma activation of
      cortical EEG can easily be demonstrated during mental activity. SIGNIFICANCE:
      These results establish the feasibility of measuring high frequency EEG rhythms
      with trans-cranial recordings, demonstrate that sustained gamma EEG activity
      correlates with mentation, and provides evidence consistent with the temporal
      binding model.

PMID- 15261860
TI  - Size matters: effects of stimulus size, duration and eccentricity on the visual
      gamma-band response.
AB  - OBJECTIVE: The effects of stimulus size, duration and eccentricity on the visual
      gamma-band response (GBR) in human EEG were investigated and compared to visual
      evoked potentials (VEPs) in order to differentiate in future (and past)
      experiments whether changes in GBRs are due to stimulus-related (exogenous) or
      cognitive effects. METHODS: EEG was recorded from 23 subjects while they
      performed a simple choice reaction time task requiring discrimination of squares
      and circles. In separate blocks stimulus size, duration, and eccentricity were
      manipulated. EEG was recorded from 64 electrodes. A wavelet transform based on
      Morlet wavelets was employed for the analysis of gamma-band activity. RESULTS:
      Amplitude of the GBR was diminished for small and peripheral stimuli. With short
      stimulus durations ON and OFF responses of the GBR merged into one peak. In
      comparison, VEP amplitudes were less susceptible to stimulus features. In
      contrast to VEP latencies, however, GBR latency did not show a lateralization for
      eccentric stimuli. CONCLUSIONS: In addition to previous experiments which have
      shown a modulation of the GBR by various cognitive processes, the present results
      demonstrate the susceptibility of the GBR in human EEG to exogenous factors, as
      numerous intracortical recordings in non-human primates have shown before. The
      results suggest that the human GBR resides in early visual areas. SIGNIFICANCE:
      The demonstration of the susceptibility of the GBR to stimulus properties implies
      that studies aimed at exploring the involvement of the GBR in information
      processing have to be designed carefully. It also constrains the localization of
      the human GBR.

PMID- 15261861
TI  - Frontal midline theta and the error-related negativity: neurophysiological
      mechanisms of action regulation.
AB  - OBJECTIVE: The error-related negativity (ERN) is an event-related potential (ERP)
      peak occurring between 50 and 100 ms after the commission of a speeded motor
      response that the subject immediately realizes to be in error. The ERN is
      believed to index brain processes that monitor action outcomes. Our previous
      analyses of ERP and EEG data suggested that the ERN is dominated by partial phase
      locking of intermittent theta-band EEG activity. In this paper, this possibility
      is further evaluated. METHODS: The possibility that the ERN is produced by phase
      locking of theta-band EEG activity was examined by analyzing the single-trial EEG
      traces from a forced-choice speeded response paradigm before and after applying
      theta-band (4-7 Hz) filtering and by comparing the averaged and single-trial
      phase-locked (ERP) and non-phase-locked (other) EEG data. Electrical source
      analyses were used to estimate the brain sources involved in the generation of
      the ERN. RESULTS: Beginning just before incorrect button presses in a speeded
      choice response paradigm, midfrontal theta-band activity increased in amplitude
      and became partially and transiently phase-locked to the subject's motor
      response, accounting for 57% of ERN peak amplitude. The portion of the theta-EEG
      activity increase remaining after subtracting the response-locked ERP from each
      trial was larger and longer lasting after error responses than after correct
      responses, extending on average 400 ms beyond the ERN peak. Multiple equivalent
      dipole source analysis suggested 3 possible equivalent dipole sources of the
      theta-bandpassed ERN, while the scalp distribution of non-phase-locked theta
      amplitude suggested the presence of additional frontal theta-EEG sources.
      CONCLUSIONS: These results appear consistent with a body of research that
      demonstrates a relationship between limbic theta activity and action regulation,
      including error monitoring and learning.

PMID- 15261862
TI  - Specific task anticipation versus unspecific orienting reaction during early
      contingent negative variation.
AB  - OBJECTIVE: To investigate whether a warning stimulus in a forewarned reaction
      time task elicits only an unspecific orienting reaction or task specific motor
      cortex activity. METHODS: We examined the time-course of alpha event-related
      desynchronization (ERD) as an indicator for primary motor cortex activation in an
      auditory contingent negative variation (CNV) paradigm with an interstimulus
      interval of 3 s in healthy subjects between 6 and 18 years using a 64 channel
      high-density sensor array. RESULTS: We replicated a wide frontal distribution for
      the initial CNV component (iCNV), while only during late CNV (lCNV) a centro
      parietal negativity resembling the 'Bereitschaftspotential' occurred. However, an
      early alpha-ERD over the central area contralateral to the side of the response
      movement followed the imperative stimulus already during the iCNV-interval. This
      early alpha-ERD was highly significantly lateralised and was even more prominent
      during iCNV than during lCNV indicating an activation of the contralateral
      sensorimotor cortex already during iCNV. CONCLUSIONS: We conclude that early task
      specific preparatory motor processes (which might reflect the retrieval of a
      motor program from memory) were elicited by the warning stimulus. These
      preparatory processes clearly exceeded an unspecific orienting reaction as early
      alpha-ERD was influenced by the side of the anticipated movement.

PMID- 15261863
TI  - Differential effects on the laser evoked potential of selectively attending to
      pain localisation versus pain unpleasantness.
AB  - OBJECTIVE: To determine the effects on the laser evoked potential (LEP) of
      selectively attending to affective (unpleasantness) versus sensory-discriminative
      (localisation) components of pain. METHODS: LEPs, elicited by painful CO2 laser
      stimulation of two areas of the right forearm, were recorded from 62 electrodes
      in 21 healthy volunteers, during three tasks that were matched for generalised
      attention: Localisation (report stimulus location), Unpleasantness (report
      stimulus unpleasantness), Control (report pain detection). LEP components are
      named by polarity, latency, and electrode. RESULTS: N300-T7 peak amplitude was
      significantly greater during Localisation than Unpleasantness. The difference in
      N300-T7 amplitude between Localisation and Control approached significance,
      suggesting an increased amplitude in Localisation compared with Control, rather
      than a reduced amplitude in Unpleasantness. Peak amplitude, latency, and
      topography of N300-FCz, P450, P600-800 (early P3) and P800-1000 (late P3) did not
      differ significantly between tasks. CONCLUSIONS: These results suggest that the
      N300-T7 LEP peak reflects the activity of cerebral generators involved in the
      localisation of pain. The topography of N300-T7 is consistent with a source in
      contralateral secondary somatosensory cortex/insula and maybe primary
      somatosensory cortex. SIGNIFICANCE: This study confirms a role of the lateral
      pain system in the localisation of pain, and distinguishes it from stimulus
      novelty or attention.

PMID- 15261864
TI  - Somatosensory evoked high-frequency oscillations in migraine patients.
AB  - OBJECTIVE: To explore additional evidence concerning generators of somatosensory
      evoked high-frequency oscillations (HFOs). METHODS: We recorded HFOs in migraine
      patients. Subjects were 19 healthy normal subjects and 19 migraineurs. Electrical
      stimuli were delivered alternately to the right and left median nerves at their
      wrists. EEGs were recorded from C3'-Fz, C4'-Fz, Erb1-Erb2, Erb2-Erb1 and Cv6-Fz
      using a 0.3 Hz low-frequency filter and a 3000 Hz high-frequency filter.
      Responses to 5000 stimuli were averaged. For separation of HFOs from underlying
      N20, the digitized wide-band signals were digitally bandpass filtered (400-800
      Hz) and averaged. RESULTS: There were no significant differences in peak
      latencies and amplitudes for N9, N13, N20 and P25 components between normal
      controls and migraineurs. Root-mean-square amplitudes for HFOs in migraineurs
      were significantly diminished compared with normal controls. CONCLUSIONS: A
      diminished inhibitory mechanism in the somatosensory system may exist in
      migraineurs. It remains to determine what cell populations contribute to
      generating HFOs. SIGNIFICANCE: This indicates that there is a dysfunction in
      cortical information processing in the somatosensory cortex of migraineurs.

PMID- 15261865
TI  - Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients
      indicate impaired frontal network processing.
AB  - OBJECTIVE: Integration of sensory information by cortical network binding appears
      to be crucially involved in target detection. Studies in schizophrenia using
      functional and diffusion tensor neuroimaging, event-related potentials and EEG
      coherence indicate an impairment of cortical network coupling in this disorder.
      Previous electrophysiological investigations in animals and humans suggested that
      gamma activity (oscillations at around 40 Hz) is essential for cortical network
      binding. Studies in medicated schizophrenia provide evidence for a reduced gamma
      activity in the context of auditory stimulus processing. This is the first
      investigation of oscillatory activations in the gamma-band in an auditory oddball
      paradigm in unmedicated schizophrenic patients. METHODS: EEG gamma-band responses
      (GBRs) of 15 drug-free schizophrenic patients and 15 age- and gender-matched
      healthy controls were compared. A wavelet transform based on Morlet wavelets was
      employed for the calculation of oscillatory GBRs. RESULTS: In response to
      standard stimuli, early evoked GBRs (20-100 ms), which are supposed to reflect
      auditory cortex activation, did not show significant group differences. However,
      schizophrenic patients showed reduced evoked GBRs in a late latency range (220
      350 ms), particularly after target stimuli. This deficit occurred over right
      frontal scalp regions. Furthermore, significant correlations were observed
      between oscillatory GBRs and clinical parameters in schizophrenic patients.
      CONCLUSIONS: The results are consistent with a relative preserved stimulus
      processing in the auditory cortex as reflected by the early GBR. The reduced late
      GBR is compatible with an abnormal interaction within a frontal lobe network, as
      was postulated by previous neuroimaging studies. SIGNIFICANCE: The present study
      provides evidence for disturbed processing within frontal cortical regions in
      unmedicated schizophrenic patients as indicated by reduced evoked EEG GBRs.

PMID- 15261866
TI  - Cognitive processes in two-point discrimination: an ERP study.
AB  - OBJECTIVE: To elucidate the temporal features of the cognitive process in two
      point discrimination (TPD). METHODS: We measured somatosensory event-related
      potentials (ERPs) in 9 subjects during the TPD task, in which we provided a pair
      of electrical pulses simultaneously, altering the distance between the
      electrodes. We analyzed the TPD-related ERPs and investigated the relationship
      between the potentials and the subjects' judgments. RESULTS: During the TPD task,
      a negative potential approximately 140 ms after the stimulation (N140) was
      enhanced as compared to a stimulus counting task. Two late positive components,
      LPC-1 and LPC-2, whose peak latencies were 300 and 500 ms, respectively, were
      identified only in the TPD task. The LPC-1 was recorded dominantly in the fronto
      central area, while the LPC-2 was detected dominantly in the centro-parietal
      area. The amplitude of the LPC-2 was significantly modulated by the degree of
      consistency in the subjects' judgment. On the other hand, these ERP components
      did not show significant difference between the alternate judgments, i.e. 'one
      point' or 'two-point' judgment. CONCLUSIONS: Our results suggest that the N140 is
      related to the attention toward the stimulation. The LPC-1 and LPC-2 are likely
      to correspond to the processes represented by P3a and P3b, based on their
      temporal and spatial behavior.

PMID- 15261867
TI  - Tempo dependence of middle- and long-latency auditory responses: power and phase
      modulation of the EEG at multiple time-scales.
AB  - OBJECTIVE: We measured the influences of power and phase modulations of
      neuroelectric activity on auditory responses to pure-tone patterns with inter
      onset intervals typical of music. METHODS: Tones were presented to 8 subjects at
      10 different tempos from 150 to 3125 ms and with random intervals. We quantified
      time-frequency (TF) power with respect to a pre-tone-onset baseline and the TF
      phase coherence across trials. Peak-to-peak event-related potential (ERP)
      amplitude values for the middle and long-latency auditory responses were obtained
      for comparison. RESULTS: ERP amplitude, size of power modulation, and amount of
      phase coherence were larger at slower tempos for the long-latency response (LLR)
      but not for the middle-latency response (MLR). Multiple regression analysis
      indicated that for MLR and LLR, phase modulation was a better predictor of ERP
      amplitude than power modulation. CONCLUSIONS: Phase modulation is a better
      predictor of ERP amplitude than power modulation for middle and long-latency
      auditory responses. SIGNIFICANCE: Lack of diminution of the MLR at fast tempos
      indicates its usefulness for studying early cortical processing of music and
      speech patterns.

PMID- 15261868
TI  - Long-range temporal correlations in alpha and beta oscillations: effect of
      arousal level and test-retest reliability.
AB  - OBJECTIVE: The aim of the present study was to evaluate test-retest reliability
      and condition sensitivity of long-range temporal correlations in the amplitude
      dynamics of electroencephalographic alpha and beta oscillations. METHODS: Twelve
      normal subjects were measured two times with a test-retest interval of several
      days. Open- and closed-eyes conditions were used, representing different levels
      of arousal. The amplitude of the alpha and beta oscillations was extracted with
      bandpass filtering and the Hilbert transform. The long-range temporal
      correlations were quantified with detrended fluctuation analysis. RESULTS: The
      amplitude dynamics of the alpha and beta oscillations demonstrated power-law long
      range temporal correlations lasting for tens of seconds. These correlations were
      degraded in the open- compared to the closed-eyes condition. Test-retest
      statistics demonstrated that the long-range temporal correlations had significant
      reliability, which was greatest in the closed-eyes condition. CONCLUSIONS: The
      presence of long-range temporal correlations indicates that the amplitude of
      neuronal oscillations at a given time is dependent on the amplitude at times as
      remote in the past as tens of seconds. The reliability of long-range temporal
      correlations suggests that the mechanisms generating the amplitude fluctuations
      are not perturbed over several days. The systematic changes in the scaling
      exponents at different levels of arousal indicate that these changes occur on
      many time scales (5-80 s) as a result of modifications in the intrinsic dynamics
      of the neuronal oscillations. SIGNIFICANCE: This study demonstrates that the
      dynamics of spontaneous neuronal oscillations possess long-range temporal
      correlations with properties suitable for functional and clinical studies.

PMID- 15261869
TI  - Evaluation of objective methods to diagnose palmar hyperhidrosis and monitor
      effects of botulinum toxin treatment.
AB  - OBJECTIVE: To evaluate (1) if laboratory tests may be a useful complement in
      diagnosing palmar hyperhidrosis and (2) if such tests can be used in the follow
      up examination of treatment effects. METHODS: Repeated measurements of
      evaporation and conductance were made in glabrous skin on hands and compared with
      subjective estimates of the degree of sweating in 20 control subjects and 20
      patients with a history of palmar hyperhidrosis. In addition, 17 patients were
      monitored for up to 6 months after treatment of the hands with botulinum toxin A.
      RESULTS: Before treatment, evaporation in the palms was higher in the patients
      than in the control subjects but skin conductance did not differ between the
      groups. After treatment both evaporation and skin conductance decreased markedly
      in the patients and then slowly returned towards pretreatment values.
      CONCLUSIONS: Measurements of evaporation, but not skin conductance, may be a
      useful objective adjunct when diagnosing palmar hyperhidrosis. Both methods can,
      however, be used to monitor intraindividual changes of sweating over time.

PMID- 15261870
TI  - Blink reflex discloses CNS dysfunction in neurologically asymptomatic patients
      with systemic sclerosis.
AB  - OBJECTIVE: To investigate trigeminal-nerve, brain-stem, and brain function, in
      order to disclose a possible nervous system involvement in neurologically
      asymptomatic systemic sclerosis (SSc) patients. METHODS: Using a standard
      electromyographic (EMG) technique, we recorded the early (R1) and late (R2)
      components of the blink reflex in 35 SSc patients with no history or signs of
      cranial-nerve impairment and 20 control subjects. SSc patients were classified as
      limited or diffuse SSc and also evaluated for disease duration, autoantibody
      pattern (ANA, ACA, Scl70) and skin score (by Rodnan modified method). RESULTS:
      Whereas no SSc patients had an abnormal R1, six (18%) had delayed R2 responses.
      We found no correlation between R2 latency and clinical or laboratory data.
      CONCLUSIONS: Whereas previous studies reported both R1 and R2 abnormalities
      (reasonably due to trigeminal neuropathy) in symptomatic SSc patients, we found
      selective abnormalities of the R2 components in asymptomatic patients. The
      selective R2 abnormality is secondary to a central dysfunction, either because of
      a direct impairment of the polysynaptic circuits in the medulla, or because of a
      decreased cortico-reticular drive on these circuits. The lack of overt trigeminal
      symptoms in our patients favours a suprasegmental dysfunction, possibly due to
      microvascular lesions disseminated in the subcortical white matter.

PMID- 15261871
TI  - A correlative electrophysiologic study of nerve fiber involvement in carpal
      tunnel syndrome using current perception thresholds.
AB  - OBJECTIVE: To relate clinical severity of idiopathic carpal tunnel syndrome (CTS)
      to current perception threshold (CPT). METHODS: Subjects were 51 patients with
      CTS (involving 51 hands), and 50 healthy control subjects (50 hands). Involved
      hands were grouped into three clinical grades (mild, moderate, severe). Using a
      neurometer (Neurotron, Baltimore, MD), we investigated the relationship between
      clinical grade and CPT abnormalities. RESULTS: In the mild CTS group, most hands
      showed CPT abnormalities only at 2000 Hz stimulation. The moderate group included
      a higher percentage of hands showing abnormalities at both 2000 and 250 Hz
      stimulation increased. The severe group included the highest percentage of hands
      with abnormal values at all frequencies tested. CONCLUSIONS: CPT showed
      abnormalities appear progressively from 'higher to lower' frequency stimulations
      relative to the increasing severity of CTS. SIGNIFICANCE: Sensory nerve fiber
      dysfunction apparently begins in larger fibers, extending stepwise to smaller
      fibers as the clinical grade of CTS progresses.

PMID- 15261872
TI  - A comparison between derivation optimization and Cz'-FPz for posterior tibial P37
      somatosensory evoked potential intraoperative monitoring.
AB  - OBJECTIVE: To compare P37 derivation optimization to Cz'-FPz. METHODS: After
      induction in 120 patients, monitoring derivations optimized by mapping FPz, Cz,
      Cz', Pz, C4', C2', C1' and C3'-mastoid to determine the P37 and N37 maximums for
      use as inputs 1 and 2 were compared to Cz'-FPz. This was repeated later in 35
      surgeries. RESULTS: Eleven optimal derivations occurred and usually differed
      between sides. Input 1 was Cz', Pz, Cz, iCi', or Ci' and input 2 was Cc', FPz,
      Ci' or Pz. Even the most frequent Cz'-Cc' derivation was optimal for both sides
      of an individual in only 17% and this was true for Cz'-FPz in only 4%.
      Optimization produced higher amplitudes than Cz'-FPz (P<0.001). The ratio was
      [squareroot of 2] : 1 in 61% of patients and > or =2:1 in 28%, approximately
      halving or quartering averaging times. Optimization assessed decussation,
      disclosing non-decussation in one patient while Cz'-FPz did not. Alterations of
      P37 topography that reduced initially optimal derivation amplitude and made a
      different derivation optimal were demonstrated by repeat optimization in 13 of 35
      patients, preventing misinterpretation in one. While also affected, Cz'-FPz
      neither detected nor adjusted for potentially misleading topographic changes.
      CONCLUSIONS: Higher amplitudes, decussation assessment and topographic adjustment
      make P37 derivation optimization superior to Cz'-FPz for monitoring this highly
      variable potential.

PMID- 15261873
TI  - The refractory period of fast conducting corticospinal tract axons in man and its
      implications for intraoperative monitoring of motor evoked potentials.
AB  - OBJECTIVE: To determine the absolute and relative refractory period (RRP) of fast
      conducting axons of the corticospinal tract in response to paired high intensity
      (HI or supramaximal) and moderate intensity (MI or submaximal) electrical
      stimuli. The importance of the refractory period of fast conducting corticospinal
      tract axons has to be considered if repetitive transcranial electrical
      stimulation (TES) is to be effective for eliciting motor evoked potentials (MEPs)
      intraoperatively. METHODS: Direct (D) waves were recorded from the epidural space
      of the spinal cord in 14 patients, undergoing surgical correction of spinal
      deformities. To assess the absolute and RRPs of the corticospinal tract, paired
      transcranial electrical stimuli at interstimulus intervals (ISI) from 0.7 to 4.1
      ms were applied. Recovery of conditioned D wave at short (2 ms) and long (4 ms)
      ISI was correlated with muscle MEP threshold. The refractory period for
      peripheral nerve was tested in comparison to that for the corticospinal tract. In
      four healthy subjects sensory nerve action potentials of the median nerve were
      studied after stimulation with paired stimuli. RESULTS: HI TES revealed a mean
      duration of 0.82 ms for the absolute refractory period of the corticospinal
      tract, while MI stimulation resulted in a mean refractory period duration of 1.47
      ms. Stimuli of HI produced faster recovery of D wave amplitude during the RRP.
      Furthermore, short trains of transcranial electrical stimuli did not elicit MEPs
      when D wave showed incomplete recovery. A similar influence of stimulus intensity
      on recovery time was found for the refractory period of peripheral nerve.
      CONCLUSIONS: The recovery of D wave amplitude is dependent upon stimulus
      intensity. High intensity produces fast recovery. This is an important factor for
      the generation of MEPs. When HI TES is used to elicit MEPs, short and long ISIs
      are equally effective. When MI TES is used to elicit MEPs, only a long ISI of 4
      ms is effective.

PMID- 15261874
TI  - Movement disorders and AIDS: a review.
AB  - Movement disorders are a potential neurologic complication of acquired immune
      deficiency syndrome (AIDS), and may sometimes represent the initial manifestation
      of HIV infection. Dopaminergic dysfunction and the predilection of HIV infection
      to affect subcortical structures are thought to underlie the development of
      movement disorders such as parkinsonism in AIDS patients. In this review, we will
      discuss the clinical presentations, etiology and treatment of the various AIDS
      related hypokinetic and hyperkinetic movement disorders, such as parkinsonism,
      chorea, myoclonus and dystonia. This review will also summarize current concepts
      regarding the pathophysiology of parkinsonism in HIV infection.

PMID- 15261875
TI  - Characterization of ataxias with magnetic resonance imaging and spectroscopy.
AB  - A wide variety of autosomal transmitted ataxias exist and their ultimate
      characterization requires genetic testing. Common clinical characteristics among
      different ataxia types complicate the choice of the appropriate genetic test.
      Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
      generally show cerebellar or cerebral atrophy and perturbed metabolite levels
      which differ between ataxias. In order to help the clinician accurately identify
      the ataxia type, reported MRI and MRS data in different brain regions are
      summarized for more than 60 different types of autosomal inherited and sporadic
      ataxias.

PMID- 15261876
TI  - Bilateral subthalamic nucleus stimulation results in reversal of alopecia in
      Parkinson's disease.
AB  - Alopecia is a rare but important side effect of anti-parkinsonian medications.
      Our patient was a 72-year-old man with advanced Parkinson's disease (PD) who
      received levodopa and anti-cholinergic drugs and whose head had become almost
      completely bald. As bilateral subthalamic nucleus (STN) stimulation produced
      improvement in his motor symptoms, his drug dosages were reduced postoperatively.
      At 8 months after surgery, hair again covered his entire head. Our study presents
      a new aspect of the benefit of STN stimulation with regard to drug-induced non
      motor symptoms in patient with PD.

PMID- 15261877
TI  - Mutational analysis of parkin gene by denaturing high-performance liquid
      chromatography (DHPLC) in essential tremor.
AB  - OBJECTIVES: To evaluate the relationship between point mutations within the
      parkin gene and essential tremor (ET). BACKGROUND: Essential tremor, the most
      common movement disorder, has long been recognised as an autosomal dominant
      disease. To date the genes involved in ET pathogenesis are still unknown. Several
      authors reported the association of ET with Parkinson's disease (PD). PATIENTS
      AND METHODS: One hundred and ten unrelated ET patients were analysed for point
      mutations within the parkin gene. Experimental conditions for DHPLC mutational
      analysis of the coding region of the parkin gene were set up. RESULTS: Neither
      obvious disruptive mutations, nor mutations previously described in patients with
      Parkinson's disease were identified in the cohort of patients analysed. DHPLC
      analysis detected two already reported polymorphisms [c.1138G>C (V380L) and
      c.1180G>A (D394N)], and four novel rare variants (frequency <1%) [c.645C>A
      (H215Q); c.847C>T (H279H); c.1393G>A (V465M) and c.2695A>G] located within exonic
      regions. Four new polymorphisms [c.413-20T>C; c.872-35G>A; c.872-68C>G; c.1286
      117A>G], and one rare variant (c.934-3C>T) were also found within intronic
      regions. CONCLUSION: Causative sequence variants in the parkin gene have not been
      identified in this cohort of Italian ET patients.

PMID- 15261878
TI  - Comparison of magnetic resonance imaging in subtypes of multiple system atrophy.
AB  - Some abnormal findings in routine MRI have been proposed as helpful
      discriminators for distinguishing multiple system atrophy (MSA) from Parkinson's
      disease (PD). However, what the most distinguishing MRI findings for MSA-p
      (parkinsonism dominant) or MSA-c (cerebellar dominant) are separately has not
      been systematically analyzed. To determine what the most helpful discriminators
      for MSA-p or MSA-c are and whether those findings are correlated with the
      presence of parkinsonism or cerebellar dysfunction, we compared 10 previously
      reported MRI findings in 36 patients with probable MSA-p, 27 patients with
      probable MSA-c and 30 patients with PD separately. In our results, hyperintense
      rim and putaminal atrophy among supratentorial parameters and the parameters of
      infratentorial atrophy were significantly prominent in MSA-p comparing to PD.
      Hyperintense rim showed the highest specificity in MSA-p patients (90.0%) with
      relatively suboptimal sensitivity (72.2%). In MSA-c, all infratentorial
      parameters had strong discriminating power comparing to PD. Signal increase in
      the middle cerebellar peduncle showed the highest specificity (100%) and had fair
      sensitivity (85.2%) in MSA-c. Compared between MSA-p and MSA-c, supratentorial
      parameters were not valid to differentiate MSA-c from MSA-p except for putaminal
      atrophy. On the contrary, infratentorial parameters were good for distinguishing
      MSA-c from MSA-p except dilatation of the fourth ventricle. Parkinsonism was not
      correlated with a hyperintense rim, but cerebellar symptoms were correlated with
      signal increase in the middle cerebellar peduncle. Our findings suggest the
      characteristic MRI can be helpful for differentiating MSA-p and MSA-c from PD,
      respectively, although they do not reflect the presence or lateralization of
      parkinsonism.

PMID- 15261879
TI  - The parkinsonian phenotype of spinocerebellar ataxia type 3 in a Taiwanese
      family.
AB  - We report a parkinsonian phenotype of spinocerebellar ataxia type 3 (SCA3) in
      three female sibs from one Taiwanese family, found in a genetic analysis of 60
      patients from 49 families with familial parkinsonism. Initially, all three
      patients presented with early onset resting tremor, rigidity, bradykinesia, and
      good response to levodopa. In the later stages, peripheral neuropathy developed
      in one sib and mild ataxia in another one. Decreased concentration of dopamine
      transporter in the striatum was demonstrated by (99m)Tc-TRODAT-1 SPECT imaging in
      the two sibs studied. Therefore, SCA3 should be considered as an important
      etiology of familial parkinsonism.

PMID- 15261880
TI  - Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's
      disease.
AB  - We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1
      (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter
      ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers.
      Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097)
      and anterior and posterior putamen (p < 0.0001) of PD patients compared to
      controls. Using the posterior putamen as the main region of interest resulted in
      the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show
      that TRODAT imaging can accurately differentiate early PD patients from controls
      and has the potential to improve the diagnosis of patients with early signs of
      PD.

PMID- 15261881
TI  - Parkinson's disease and thyroid dysfunction.
AB  - BACKGROUND: Although no causal linkage between hypothyroidism and Parkinson's
      disease (PD) has been demonstrated so far, both share common manifestations and
      coexistence can be a source of diagnostic delay and confusion. PURPOSE: To assess
      thyroid function in patients with PD. SCOPE: Ninety-five PD patients and 102 age
      matched controls were assessed for hypothyroidism through clinical evaluation and
      laboratory screening. RESULTS: In the PD group 13.7% were hypothyroid versus
      10.8% in the control group. Statistical analysis did not show a significant
      difference (p = 0.3681). CONCLUSION: Although hypothyroidism was not more
      prevalent in our PD patients in comparison with the control group, we believe
      that given the potential overlap of symptoms and signs, thyroid function should
      be assessed in patients showing worsening of symptoms that cannot be explained by
      disease progression or resistance to therapy adjustment; screening should take
      into account the particular acute effect of levodopa on serum TSH levels.

PMID- 15261882
TI  - Dopamine-transporter imaging and visuo-motor testing in essential tremor,
      practical possibilities for detection of early stage Parkinson's disease.
AB  - BACKGROUND: Essential tremor (ET) is often an alternative diagnosis to
      Parkinson's disease (PD) and some ET patients may later develop PD. Unlike the
      former, PD patients have deficient visuo-motor coordination (VMC). Recently, we
      have attempted to exploit this difference in order to detect PD in ambiguous
      neurological cases. OBJECTIVE: To assess the possibility of using VMC testing for
      screening ET patients prior to [123I]-FP-CIT SPECT imaging. METHODS: Ten
      clinically diagnosed ET patients who showed deficient VMC were subjected to [123I
      FP-CIT] SPECT imaging. We expected these patients to show subnormal striatal
      ligand uptake, as in PD. RESULTS: We found decreased [123I]-FP-CIT uptake in 80%
      of the patients. A significant correlation between ligand uptake and VMC was
      observed. CONCLUSIONS: Impaired VMC is a pertinent indication for further SPECT
      imaging in patients with ET, in order to establish a diagnosis of incipient PD.

PMID- 15261884
TI  - Neural tube programming and craniofacial cleft formation. I. The neuromeric
      organization of the head and neck.
AB  - This review presents a brief synopsis of neuromeric theory. Neuromeres are
      developmental units of the nervous system with specific anatomic content.
      Outlying each neuromere are tissues of ectoderm, mesoderm and endoderm that bear
      an anatomic relationship to the neuromere in three basic ways. This relationship
      is physical in that motor and sensory connections exist between a given
      neuromeric level and its target tissues. The relationship is also developmental
      because the target cells exit during gastrulation precisely at that same level.
      Finally the relationship is chemical because the genetic definition of a
      neuromere is shared with those tissues with which it interacts. The model
      developed by Puelles and Rubenstein is used to describe the neuroanatomy of the
      neuromeres. Although important details of the model are currently being refined
      it has immediate clinical relevance for practicing clinicians because it permits
      us to understand many pathologic states as relationships between the brain and
      the surrounding tissues. Relationships between the processes of neurulation and
      gastrulation have been presented to demonstrate the manner in which neuromeric
      anatomy is established in the embryo. We are now in a position to describe in
      detail the static anatomic structures that result from this system. The
      neuromeric 'map' of craniofacial bones, dermis, dura, muscles, and fascia will be
      the subject of the next part of this series.

PMID- 15261885
TI  - Distinguishing PANDAS from Sydenham's chorea: case report and review of the
      literature.
AB  - Children with Sydenham's chorea and PANDAS (Pediatric autoimmune neuropsychiatric
      disorders associated with streptococcal throat infections) share an array of
      neuropsychiatric symptoms and distinguishing one from the other, especially at
      onset can prove challenging. It is, however, important to distinguish between
      these two post-streptococcal disorders since their response to therapy differs.
      Children with Sydenham's chorea require long-term benzathine penicillin
      prophylaxis to reduce the risk of rheumatic heart disease. In contrast, the
      efficacy of penicillin prophylaxis in preventing tic or obsessive-compulsive
      symptom exacerbations in children with PANDAS remains doubtful. Immunomodulatory
      therapies such as plasma exchange and intravenous immunoglobulin have shown to
      reduce neuropsychiatric symptom severity in children with PANDAS. Tonsillectomy
      may also represent an effective treatment option in children severely affected by
      PANDAS. We present this case to demonstrate the pitfalls in differentiating
      between these two closely associated conditions in a developing country where the
      prevalence of rheumatic fever is high.

PMID- 15261886
TI  - Diagnostic difficulties in a case of primary systemic carnitine deficiency with
      idiopathic dilated cardiomyopathy.
AB  - Blood spot carnitine profiles are widely used to screen for disorders of fatty
      acid oxidation. This case report emphasizes that a borderline concentration of
      free carnitine does not exclude the diagnosis of primary carnitine deficiency.
      Concurrent measurement of carnitine in the plasma and urine is a more sensitive
      test.

PMID- 15261887
TI  - Early onset Charcot-Marie-Tooth type 1B disease caused by a novel Leu190fs
      mutation in the myelin protein zero gene.
AB  - The spectrum of Charcot-Marie-Tooth (CMT) phenotypes segregating with mutations
      in the Myelin Protein Zero (MPZ) gene is wide and ranges from congenital
      hypomyelinating neuropathy (CHN) through demyelinating form of CMT to the axonal
      type of CMT disease. Within 94 MPZ gene mutations reported up to now, only a few
      were identified in the exon 4 of the MPZ gene. In this study we have identified a
      novel Leu190fs mutation in the MPZ gene. The Leu190fs mutation was found in a 14
      year-old girl suffering from Charcot-Marie-Tooth type 1 disease (CMT1) with onset
      in early infancy. Similarly to the other MPZ gene frame-shift mutations reported
      as far the Leu190fs seems to have a dominant negative effect.

PMID- 15261888
TI  - Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the
      nervous system?
AB  - Tissue-type plasmingen activator (tPA) is a highly specific serine proteinase
      that activates the zymogen plasminogen to the broad-specificity proteinase
      plasmin. tPA is found in the blood, where its primary function is as a
      thrombolytic enzyme, as well as in the central nervous system (CNS), where it
      promotes events associated with synaptic plasticity and cell death in a number of
      settings, such as cerebral ischemia and seizures. Neuroserpin is a fully
      inhibitory serine proteinase inhibitor (serpin) that reacts preferentially with
      tPA, and is located in regions of the brain where either tPA message or tPA
      protein are also found, suggesting that neuroserpin is the selective inhibitor of
      tPA in the CNS. There is a growing body of evidence demonstrating the
      participation of tPA in a number of physiologic and pathologic events in the CNS,
      and the role of neuroserpin as the natural regulator of tPA's activity in these
      processes.

PMID- 15261889
TI  - The functions of plasminogen in cardiovascular disease.
AB  - Plasminogen (Plg) and its derivative serine protease, plasmin, together with the
      activators, inhibitors, modulators, and substrates of the Plg network, are
      postulated to regulate a wide variety of biologic responses that could influence
      cardiovascular disease. The development of Plg-deficient mice has provided an
      incisive approach to test these proposed functions in vivo. Several different
      models of atherosclerosis, restenosis, aneurysm, and thrombosis have been
      analyzed in these mice and have demonstrated profound effects of Plg on these
      events as well as on the inflammatory response, which contributes to these
      cardiovascular diseases. Plasmin (ogen) may influence the progression of
      cardiovascular diseases through its degradation of matrix proteins, including
      fibrin; its activation of matrix metalloproteinases; its regulation of growth
      factor and chemokine pathways; or its influence on directed cell migration.
      Dissection of these mechanisms represents a future challenge toward understanding
      the roles of Plg in vivo.

PMID- 15261890
TI  - Cellular and molecular mechanisms of atherosclerosis with mouse models.
AB  - Recently, there has been an explosion in the number of in vivo studies using
      genetically engineered mouse models. Atherosclerosis research using mice began
      with the invention of traditional atherosclerotic mice including low-density
      lipoprotein receptor knockout (LDLR(-/-)) and apolipoprotein E knockout (apoE(-/
      )) mice, which provided tremendous progress in atherosclerosis research. Since
      then, a number of modified atherosclerotic mouse models have been reported to
      generate lesions that more closely characterize human atherosclerotic lesions.
      Those modifications include inflammation, hypertension, proteinases and
      extracellular matrix, glucose metabolism, and immune systems. This article
      focuses on various kinds of mouse models with atherosclerosis and their
      contributions to the current advances of research.

PMID- 15261891
TI  - Lipoxygenase pathways in atherogenesis.
AB  - 15-lipoxygenase-1 (also known as 12/15-LO in mice) and 5-LO/5-LO-activating
      protein (FLAP) cascades play central roles in low-density lipoprotein oxidation
      and leukotriene biosynthesis, respectively. Several genetic and expression
      studies unraveling an association of the 5-LO/FLAP pathway to human
      cardiovascular disease have surfaced recently. Experimental studies in 12/15-LO
      knockout, 15-LO-1 transgenic, and 5-LO knockout mice on atherosclerotic
      backgrounds combined with gene expression data in human coronary artery disease
      have created compelling links that these pathways participate in the etiologic
      progression. However, a few conflicting studies and several unexplained
      mechanistic issues need to be resolved prior to assigning firm roles for LOs in
      cardiovascular disease. Development of novel pharmacologic tools to dissect the
      individual enzymes and receptors in the LO pathways should improve understanding
      of the individual components in the inflammatory aspects of atherosclerosis
      disease progression.

PMID- 15261892
TI  - Plasminogen activator inhibitor 1, fibrin, and the vascular response to injury.
AB  - Intravascular fibrin deposition is believed to play an important role in the
      development of intimal hyperplasia, which is a hallmark of several human vascular
      disorders, including atherosclerosis and restenosis after balloon angioplasty.
      Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor or tissue- and
      urinary-type plasminogen activator, plays a key role in fibrin homeostasis by
      controlling plasmin formation. PAI-1 may also modulate vascular pathology via
      alternative pathways, such as inhibiting activated protein C and altering
      interactions between vascular smooth muscle cells and the extracellular matrix.
      The diverse functional profile of PAI-1 likely accounts for the variation
      observed in its impact on intimal hyperplasia in different disease models. This
      review examines recent studies addressing the vascular function of PAI-1, and
      those assessing the role of fibrin as a downstream mediator of PAI-1's effects.

PMID- 15261893
TI  - Endothelial lipase: a modulator of lipoprotein metabolism upregulated by
      inflammation.
AB  - Both acute and chronic inflammatory states are associated with decreased levels
      of high-density lipoprotein (HDL) cholesterol, yet the underlying mechanism is
      poorly understood. Endothelial lipase (EL), a recently described member of the
      triglyceride lipase family, has been shown to be a key enzyme in HDL metabolism.
      Expression of EL by endothelial cells is upregulated by proinflammatory cytokines
      and is associated with increased EL-specific triglyceride and phospholipase
      activity in vitro. Thus, EL may play an important role in lipid metabolism and
      energy homeostasis in states of acute and chronic inflammation.

PMID- 15261894
TI  - Obesity relationships with community design, physical activity, and time spent in
      cars.
AB  - BACKGROUND: Obesity is a major health problem in the United States and around the
      world. To date, relationships between obesity and aspects of the built
      environment have not been evaluated empirically at the individual level.
      OBJECTIVE: To evaluate the relationship between the built environment around each
      participant's place of residence and self-reported travel patterns (walking and
      time in a car), body mass index (BMI), and obesity for specific gender and
      ethnicity classifications. METHODS: Body Mass Index, minutes spent in a car,
      kilometers walked, age, income, educational attainment, and gender were derived
      through a travel survey of 10,878 participants in the Atlanta, Georgia region.
      Objective measures of land use mix, net residential density, and street
      connectivity were developed within a 1-kilometer network distance of each
      participant's place of residence. A cross-sectional design was used to associate
      urban form measures with obesity, BMI, and transportation-related activity when
      adjusting for sociodemographic covariates. Discrete analyses were conducted
      across gender and ethnicity. The data were collected between 2000 and 2002 and
      analysis was conducted in 2004. RESULTS: Land-use mix had the strongest
      association with obesity (BMI >/= 30 kg/m(2)), with each quartile increase being
      associated with a 12.2% reduction in the likelihood of obesity across gender and
      ethnicity. Each additional hour spent in a car per day was associated with a 6%
      increase in the likelihood of obesity. Conversely, each additional kilometer
      walked per day was associated with a 4.8% reduction in the likelihood of obesity.
      As a continuous measure, BMI was significantly associated with urban form for
      white cohorts. Relationships among urban form, walk distance, and time in a car
      were stronger among white than black cohorts. CONCLUSIONS: Measures of the built
      environment and travel patterns are important predictors of obesity across gender
      and ethnicity, yet relationships among the built environment, travel patterns,
      and weight may vary across gender and ethnicity. Strategies to increase land-use
      mix and distance walked while reducing time in a car can be effective as health
      interventions.

PMID- 15261895
TI  - Body and soul. A dietary intervention conducted through African-American
      churches.
AB  - OBJECTIVES: Body and Soul was a collaborative effort among two research
      universities, a national voluntary agency (American Cancer Society), and the
      National Institutes of Health to disseminate and evaluate under real-world
      conditions the impact of previously developed dietary interventions for African
      Americans. METHODS: Body and Soul was constructed from two successful research
      based interventions conducted in African-American churches. Components deemed
      essential from the prior interventions were combined, and then tested in a
      cluster randomized-effectiveness trial. The primary outcome was fruit and
      vegetable intake measured with two types of food frequency questionnaires at
      baseline and 6-month follow-up. RESULTS: At the 6-month follow-up, intervention
      participants showed significantly greater fruit and vegetable (F&V) intake
      relative to controls. Post-test differences were 0.7 and 1.4 servings for the 2
      item and 17-item F&V frequency measures, respectively. Statistically significant
      positive changes in fat intake, motivation to eat F&V, social support, and
      efficacy to eat F&V were also observed. CONCLUSIONS: The results suggest that
      research-based interventions, delivered collaboratively by community volunteers
      and a health-related voluntary agency, can be effectively implemented under real
      world conditions.

PMID- 15261896
TI  - The prevention paradox, traffic safety, and driving-while-intoxicated treatment.
AB  - BACKGROUND: In San Juan County, New Mexico, a 28-day jail/treatment program for
      first-time driving-while-intoxicated (DWI) offenders was established in 1994 to
      reduce both DWI recidivism and alcohol-related crashes. This paper assesses the
      impact of the program on both outcomes. METHODS: The data are composed of driving
      records of all people arrested for DWI in San Juan County from August 1994
      through December 2001. Subsequent re-arrests and crashes were analyzed to compare
      people who had been sentenced to the jail/treatment program and those who had
      not. Kaplan-Meier survival curves and Cox proportional hazards regression
      analyses were used. Covariates included age, gender, blood alcohol content (BAC),
      number of prior arrests, and ethnicity (Native American, non-Hispanic white, and
      Hispanic). RESULTS: Re-arrest rates were significantly lower for the treatment
      than the nontreatment group. Each of the three major ethnic groups showed similar
      effects. This was not observed for subsequent alcohol-related crashes, possibly
      as a result of insufficient numbers. BAC and number of previous arrests were,
      however, significant risk factors for subsequent crashes. Finally, although BAC
      and previous arrests were important risk factors for subsequent crashes, the vast
      majority of subsequent alcohol-related crashes occurred among people in the
      intermediate risk ranges. CONCLUSIONS: The jail/treatment program is effective in
      reducing the probability of DWI re-arrests. The evidence with respect to crashes
      is equivocal. That most crashes occur to people in the intermediate risk range
      exemplifies the prevention paradox, and means that the courts, which deal most
      severely with high-risk individuals, cannot be expected to have a major impact on
      alcohol-related crashes.

PMID- 15261897
TI  - Public health and correctional collaboration in tuberculosis control.
AB  - OBJECTIVE: To assess the extent that 20 large jail systems and their respective
      public health departments collaborate to prevent and control tuberculosis (TB).
      METHODS: Data were collected through questionnaires sent to jail medical
      directors and TB control directors, interviews, and on-site observation in each
      of the jails. RESULTS: Only 35% of jail systems and health departments reported
      having effective collaboration in TB prevention and control activities. Four
      barriers were reported by a majority of the jail systems: funding (65%), staffing
      (60%), staff training (55%), and communication (55%). Lack of advance notice of a
      patient's release was rated as the greatest barrier to discharge planning. Fifty
      percent of the jail systems reported that they scheduled appointments for soon-to
      be released patients with TB, and 10% did so for patients being treated for
      latent TB infection (LTBI). Fewer patients actually received appointments: seven
      (39%) of 33 released patients with TB had documentation in their medical record
      of appointments, and one of 46 released patients on treatment for LTBI had them.
      Characteristics associated with increased collaboration include having designated
      liaisons between jail systems and health departments and holding periodic
      meetings of staff. CONCLUSIONS: Health departments and jail systems in the same
      jurisdiction have implemented recommendations regarding collaboration to a
      limited extent. Such collaborations need strengthening, especially discharge
      planning and evaluation of TB control activities.

PMID- 15261898
TI  - Prevention of smoking-related deaths in the United States.
AB  - BACKGROUND: Tobacco is the leading cause of death in the United States. The
      majority of people who smoke begin before age 18. OBJECTIVE: Determine the number
      of smoking-attributable deaths and years of potential life lost (YPLL) in adults
      that might be saved through interventions to reduce smoking prevalence among
      children and adolescents. METHODS: Calculation of the smoking-attributable
      mortality and years of potential life lost by age 85 among the cohort of people
      aged 18 in 2000. RESULTS: By age 85, there would be 127,670 smoking-attributable
      deaths among women and 284,502 deaths among men, for a total 412,172 smoking
      attributable deaths in the United States among the cohort of 3,964,704 people
      aged 18 years alive in 2000. Through large-scale multimedia campaigns and a $1
      increase in the price per pack of cigarettes, smoking prevalence could be reduced
      by 26% and would result in an annual savings of 108,466 lives and 1.6 million
      YPLL. CONCLUSIONS: Interventions to decrease smoking prevalence among children
      and adolescents can have large effects on adult mortality.

PMID- 15261899
TI  - Home smoking restrictions. Problems in classification.
AB  - BACKGROUND: Evidence of the effectiveness of smoking restrictions in workplaces
      and other public places is creating awareness of the role of bans in private
      spaces. The purpose of this study was to examine who is affected by strict home
      smoking bans at the household level. METHODS: Using the 1998/1999 Tobacco Use
      Supplement to the U.S. Current Population Survey, we examined the characteristics
      of 43,613 households with two or more adults who responded to the home ban
      question. Analyses were conducted in 2003-2004. RESULTS: An estimated 12% of
      sample households provided inconsistent reports about home smoking bans.
      Multimember households with smokers were substantially less likely to
      consistently report strict home bans. Discrepancies vary systematically by
      smoking behavior, socioeconomic status, and race/ethnicity. Children living with
      smokers are especially at risk of inconsistent adult reports. CONCLUSIONS:
      Analyses should not rely on individual reports of home bans, especially in
      households with smokers and children. Policies should be directed toward
      educating members of households with smokers and children about the importance of
      household bans.

PMID- 15261900
TI  - Cervical cancer among Hmong women in California, 1988 to 2000.
AB  - BACKGROUND: The Hmong immigrated to the United States from Laos after the Vietnam
      conflict ended. Hmong encounter numerous readjustment issues, including health
      care. Traditional Hmong health beliefs and practices encompass more spiritual
      than biological etiologies. Hmong usually seek the first course of treatment from
      traditional healers, as they had in Laos. This practice delays early diagnosis
      and treatment of disease because biomedicine is used only as a last resort. This
      study examined cervical cancer incidence, mortality, and other tumor
      characteristics in the Hmong female population of California between 1988 and
      2000. METHODS: Data from the California Cancer Registry were used to calculate
      annual average incidence, mortality, and age-specific rates for Hmong women
      diagnosed with cervical cancer. The population at risk was estimated with linear
      interpolation using data from the 1990 and 2000 censuses. RESULTS: Hmong women
      experienced incidence and mortality rates three and four times higher than
      Asian/Pacific Islander and non-Hispanic white women, respectively. Fifty-one
      percent of Hmong women chose no treatment, compared to 5.8% for Asian/Pacific
      Islander women and 4.8% for non-Hispanic white women. Hmong women aged >/= 40
      years carried an unequal burden of cervical cancer. They were more likely to be
      diagnosed with cervical cancer at later stages and poorer histologic grades, and
      had a lower survival rate than younger Hmong females. CONCLUSIONS: Cervical
      cancer is clearly a public health issue that threatens the health and well-being
      of Hmong women. Culturally sensitive screening and prevention programs need to be
      developed to target older Hmong women using bilingual and bicultural Hmong women
      health educators using verbal communication.

PMID- 15261901
TI  - Disaggregating data on Asian and Pacific Islander women to assess cancer
      screening.
AB  - BACKGROUND: Although incidence of cancer is increasing among Asian-American and
      Pacific-Islander (AAPI) women, their low cancer screening rates are inadequately
      addressed. Furthermore, the traditional approach of studying the diverse AAPI
      nationalities as one group hides important intra- and inter-group ethnic
      differences in cancer screening, as well as lack of representativeness because
      the surveys are not administered in any AAPI language. To address these problems,
      this study compared cancer screening rates among particular AAPI groups and non
      AAPIs living in an ethnically diverse region. METHODS: This study was conducted
      in 2001-2002 using data from the 1999-2000 Los Angeles County Health Survey, a
      population-based telephone survey that relied on random-digit-dialing techniques.
      Cervical and breast cancer-screening rates were measured, and key determinants of
      screening using bivariate analyses and multivariate logistic regression were
      assessed. RESULTS: AAPIs had lower screening rates than whites, with significant
      variation among AAPI subgroups. Moreover, AAPI women were less likely to have
      undergone cervical cancer screening compared to white women, independent of major
      demographic, socioeconomic, and health status factors. Determinants for receipt
      of cancer screening differed for AAPIs and whites. Immigration factors were
      significant barriers to cancer screening for AAPIs. CONCLUSIONS: These findings
      support the evidence of disparities in receipt of cancer screening services among
      subgroups of AAPI women. Additionally, these findings highlight the importance of
      disaggregating the heterogeneous AAPI population to identify higher-risk
      subgroups and facilitate development of effective targeted interventions.

PMID- 15261903
TI  - Disparities in immunizations among elderly Medicare beneficiaries, 2000 to 2002.
AB  - BACKGROUND: Research reveals that influenza and pneumococcal immunization rates
      among blacks, Asians, and Hispanics significantly trail those of whites. This
      2003 study examines recent trends and disparities for influenza and pneumococcal
      immunizations among elderly, non-institutionalized Medicare beneficiaries.
      METHODS: National samples of approximately 179,000 Medicare fee-for-service
      beneficiaries were surveyed by mail and telephone each year from 2000 to 2002.
      Outcomes include self-reported influenza immunization in the previous year and
      receipt of a pneumococcal immunization ever. RESULTS: Influenza immunization
      dipped in 2001 (69%) and almost rebounded to its 2000 level (73%) in 2002 (72%).
      Very substantial racial and ethnic disparities in the receipt of this preventive
      service exist between non-Hispanic blacks and Hispanics relative to non-Hispanic
      whites. Pneumococcal immunization increased by 2% annually (61%, 63%, and 65%)
      for the same years. However, very substantial racial and ethnic disparities in
      the receipt of this preventive service also exist between non-Hispanic blacks,
      Asians/Pacific Islanders, and Hispanics relative to non-Hispanic whites.
      CONCLUSIONS: Younger, healthier, elderly persons must be encouraged to receive
      these immunizations to achieve the 2010 goal of 90% immunization. To reach that
      goal with no disparities, special efforts will be needed to target racial/ethnic
      minorities.

PMID- 15261902
TI  - Physical inactivity and overweight among Los Angeles County adults.
AB  - OBJECTIVES: The present study examines sociodemographic, health status, health
      behavioral, and health-related self-perception correlates of physical inactivity
      in a large, multiethnic urban population. METHODS: A random-digit-dialed
      telephone survey of a representative sample of 8353 Los Angeles County adults
      aged >/= 18 years was conducted between September 17, 1999 and December 31, 2000.
      Data were analyzed to assess the prevalence and identify independent correlates
      of physical inactivity, defined as <10 minutes of continuous physical activity
      weekly ("sedentary"). RESULTS: Overall, the prevalence of sedentary adults was
      41%. Lower educational attainment, female gender, advancing age, non-U.S.
      birthplace, poorer self-perceived health status, self-perceived depression,
      smoking, leisure-time television watching/computer use, and receiving a diabetes
      diagnosis were significantly related to sedentariness in both bivariate and
      multivariate analyses. CONCLUSIONS: Mental and physical health status were
      prominent correlates of sedentariness. Lower socioeconomic class was also
      associated with sedentary behavior. Further research is needed to understand the
      relationship between self-perceived overweight and sedentary behavior.

PMID- 15261904
TI  - Immunization requirements for childcare programs. Are they enough?
AB  - BACKGROUND: School immunization legislation has resulted in high vaccination
      coverage rates and low rates of vaccine-preventable disease among school
      children. Similar legislation has been directed toward children in licensed and
      regulated childcare programs. The purpose of this investigation was to compare
      immunization coverage among children in and not in childcare. METHODS: For 18
      months during 2001 and 2002, the National Immunization Survey (NIS), a random
      digit-dialing telephone survey, collected information on children aged 19 through
      35 months, including data on enrollment in childcare. Data were analyzed
      retrospectively to determine coverage at 24 months and at the time of the survey.
      Children were considered up-to-date if they had received all recommended
      immunizations for their age. RESULTS: Of the eligible NIS respondents, about 41%
      had a child in childcare at the time of or before the survey. Retrospective
      analysis of children at 24 months showed no significant differences in coverage
      between those in and not in childcare (73.1% vs 71.9%). Likewise, analysis of
      coverage at the time of the survey revealed no significant differences (76.4% vs
      72.6%). CONCLUSIONS: Immunization legislation and regulations have been
      successful in increasing coverage rates in the school population. Similar
      legislation for childcare facilities appears not to have been as effective. Given
      these findings, it seems that new strategies are needed to increase coverage in
      preschool children.

PMID- 15261905
TI  - Healthy passages. A multilevel, multimethod longitudinal study of adolescent
      health.
AB  - PURPOSE: To provide an overview of a multisite, long-term study that focuses on
      risk and protective factors, health behaviors (e.g., dietary practices, physical
      inactivity, tobacco use, and violent activity), and health outcomes (e.g.,
      diabetes, obesity, and sexually transmitted diseases) for a fifth-grade cohort to
      be followed biennially from ages 10 to 20 years. METHODS: A two-stage probability
      sampling procedure was used to select 5250 fifth-grade students from schools in
      Birmingham AL, Houston TX, and Los Angeles CA to ensure a sufficient sample size
      of African Americans, Hispanics, and non-Hispanic whites, to support precise
      statistical inferences. Computer-assisted technology was used to collect data
      from children and their primary caregivers. Teachers and other school personnel
      responded to questionnaires, and observational procedures were used to obtain
      information about schools and neighborhoods. RESULTS: To exploit the multilevel,
      multimethod structure of the data, statistical models include latent-growth
      mixture modeling, multilevel modeling, time-series analysis, survival analysis,
      latent transition analysis, and structural equation modeling. Analyses focus both
      on the co-occurrence and predictors of growth trajectories for different health
      behaviors across time. CONCLUSIONS: By using a prospective research design and
      studying the predictors and time course of multiple health behaviors with a
      multilevel, multimethod assessment protocol, this research project could provide
      an empirical basis for effective social and educational policies and intervention
      programs that foster positive health and well-being during both adolescence and
      adulthood.

PMID- 15261906
TI  - Firearm ownership and storage practices, U.S. households, 1992-2002. A systematic
      review.
AB  - BACKGROUND: Because the presence and improper storage of household firearms are
      risk factors for injury, it is important to understand the prevalence of
      ownership and storage practices within households to help guide intervention
      development. This systematic review of published articles (1992 to 2002) provides
      prevalence estimates of firearm ownership and storage practices in U.S.
      households. METHODS: A search of bibliographic databases (MedLine, CINAHL,
      PsycInfo, Sociological Abstracts) was completed in January 2003. RESULTS:
      Although all were cross-sectional, the 42 articles included in this review varied
      in type; there were seven national and five state prevalence studies, as well as
      studies using clinic-based convenience samples (n =14) and samples of
      professionals (n =10). Published studies indicate that firearms are present in
      about one third of U.S. households. Handguns in particular are present in more
      than half of U.S. households with firearms, or about 19% of all U.S. households.
      The prevalence of firearms and handguns in households with young people was
      similar to the prevalence overall. Firearm ownership was highest in the South.
      CONCLUSIONS: Although the methodologic rigor of published articles varies
      substantially, the literature clearly establishes that firearms are common in
      U.S. households, even in the homes of medical professionals and those with
      children.

PMID- 15261907
TI  - Local knowledge to enable local action.

PMID- 15261908
TI  - Provider compliance with a guideline for treating tobacco use among adults.

PMID- 15261909
TI  - 35th Bethesda Conference. Cardiology's Workforce Crisis: a pragmatic approach.
      Bethesda, Maryland, 17-18 October 2003.

PMID- 15261910
TI  - Working group 1: How to increase the output of cardiologists.

PMID- 15261911
TI  - Working group 2: How to encourage more women to choose a career in cardiology.

PMID- 15261912
TI  - Working group 3: How to encourage more minorities to choose a career in
      cardiology.

PMID- 15261913
TI  - Working group 4: International medical graduates and the cardiology workforce.

PMID- 15261914
TI  - Working group 5: Innovative care team models and processes that might enhance
      efficiency and productivity.

PMID- 15261915
TI  - Working group 6: The role of technology to enhance clinical and educational
      efficiency.

PMID- 15261916
TI  - Working group 7: Enhancing the job "matching" process.

PMID- 15261917
TI  - Working group 8: Defining the different types of cardiovascular specialists and
      developing a new model for training general clinical cardiologists.

PMID- 15261918
TI  - Summary of Task Force recommendations to address the growing shortage of
      cardiologists.

PMID- 15261919
TI  - Cardiac protection during acute myocardial infarction: where do we stand in 2004?
AB  - Despite better outcomes with early coronary artery reperfusion for the treatment
      of acute ST-elevation myocardial infarction (MI), morbidity and mortality from
      acute myocardial infarction (AMI) remain significant, the incidence of congestive
      heart failure continues to increase, and there is a need to provide better
      cardioprotection (therapy that reduces the amount of necrosis that may be coupled
      with better clinical outcome) in the setting of AMI. Since the introduction of
      the concept of cardiac protection over a quarter of a century ago, various
      interventions have been investigated to reduce myocardial infarct size.
      Intravenous beta-blockers administered in the early hours of infarction were
      clearly shown to be of benefit. Intravenous adenosine appeared promising for
      anterior wall AMIs, as did cariporide in some studies. Glucose-insulin-potassium
      infusion was beneficial in certain subgroups of patients, particularly diabetics.
      A variety of other medications were studied with negative or marginal results.
      The best strategy to limit infarct size is early reperfusion with percutaneous
      coronary stenting or thrombolytic therapy. Stenting is superior and should be
      adopted whenever there is a qualified laboratory available. Available resources
      should focus on decreasing time from onset of symptoms to start of reperfusion
      and maintaining vessel patency. Future studies powered to better assess clinical
      outcome are needed for adjunctive therapy with adenosine, K(ATP) channel openers,
      Na(+)/H(+) exchange inhibitors, and hypothermia.

PMID- 15261921
TI  - Rescue angioplasty: does the concept need to be rescued?

PMID- 15261920
TI  - A randomized trial of rescue angioplasty versus a conservative approach for
      failed fibrinolysis in ST-segment elevation myocardial infarction: the
      Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial.
AB  - OBJECTIVES: We sought to compare emergency coronary angiography with or without
      rescue percutaneous coronary intervention (PCI) with conservative treatment in
      patients with failed fibrinolysis complicating ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Most patients with STEMI receive fibrinolytic
      therapy and aspirin. The management of failed fibrinolysis is unclear. METHODS: A
      total of 307 patients with STEMI and failed fibrinolysis were randomized to
      emergency coronary angiography with or without rescue PCI or conservative
      treatment. RESULTS: Thirty-day all-cause mortality was similar in the rescue and
      conservative groups (9.8% vs. 11%, p = 0.7, risk difference [RD] 1.2%, 95%
      confidence interval [CI] -5.8 to 8.3). The composite secondary end point of
      death/re-infarction/stroke/subsequent revascularization/heart failure occurred
      less frequently in the rescue group (37.3% vs. 50%, p = 0.02, RD 12.7%, 95% CI
      1.6 to 23.5), driven by less subsequent revascularization (6.5% vs. 20.1%, p <
      0.01, RD 13.6%, 95% CI 6.2 to 21.4). Re-infarction and clinical heart failure
      were less common in the rescue group (7.2% vs. 10.4%, p = 0.3, RD 3.2%, 95% CI 
      3.3 to 9.9; and 24.2% vs. 29.2%, p = 0.3, RD 5.7%, 95% CI -4.3 to 15.6,
      respectively). Strokes and transfusions were more common in the rescue group
      (4.6% vs. 0.6%, p = 0.03, RD 3.9%, 95% CI 0.5 to 8.6; and 11.1% vs. 1.3%, p <
      0.001, RD 9.8%, 95% CI 4.9 to 19.9, respectively). Left ventricular function at
      30 days was the same in the two groups. CONCLUSIONS: Rescue angioplasty did not
      improve survival by 30 days, but improved event-free survival, almost completely
      due to a reduction in subsequent revascularization. Rescue angioplasty was
      associated with more strokes and more transfusions and did not result in
      preservation of left ventricular systolic function at 30 days.

PMID- 15261922
TI  - The decrease of plaque volume during percutaneous coronary intervention has a
      negative impact on coronary flow in acute myocardial infarction: a major role of
      percutaneous coronary intervention-induced embolization.
AB  - OBJECTIVES: The aim of this study was to evaluate how decreased plaque volume
      during percutaneous coronary intervention (PCI) affects coronary flow in patients
      with acute myocardial infarction (AMI). BACKGROUND: Coronary flow after
      reperfusion therapy is a major determinant of clinical outcomes in patients with
      AMI. However, little is still known about the changes in coronary flow that
      appear after PCI in response to the decreased plaque during the procedure.
      METHODS: The study group comprised 60 patients with AMI who underwent pre- and
      post-PCI intravascular ultrasound (IVUS). Qualitative and quantitative analyses
      were performed on all IVUS procedures. External elastic membrane volume (EEMV),
      lumen volume (LV), and plaque volume (PV) were measured every 1.0 mm to include
      the lesion and reference segments 3.0 mm proximal and distal to the lesion. The
      difference between pre- and post-PCI PV was defined as the index of the decrease
      in plaque volume (DeltaPV). The corrected TIMI frame count (CTFC) was used to
      evaluate coronary flow after PCI. RESULTS: Plaque volume was decreased at post
      PCI IVUS in all 60 patients. Inadequate reflow (CTFC >40) was observed in 13
      patients (21.7%). The decrease in PV was significantly larger in patients with
      inadequate reflow than in those with reflow (49.4 +/- 18.9 vs. 31.7 +/- 15.5
      mm(3), p = 0.0010). Also, DeltaPV was significantly correlated with CTFC after
      PCI (r = 0.415, p = 0.0012). CONCLUSIONS: The decrease in PV during PCI has a
      negative impact on coronary flow after PCI in patients with AMI. Embolization
      induced by PCI may occur in all patients with AMI.

PMID- 15261923
TI  - Frequency, correlates, and clinical implications of myocardial perfusion after
      primary angioplasty and stenting, with and without glycoprotein IIb/IIIa
      inhibition, in acute myocardial infarction.
AB  - OBJECTIVES: We sought to determine the prognostic importance of myocardial
      reperfusion after various contemporary interventional strategies in patients with
      acute myocardial infarction (AMI). BACKGROUND: The frequency, correlates, and
      clinical implications of myocardial perfusion after primary angioplasty in AMI
      have not been examined in a large-scale prospective study. Similarly, whether
      glycoprotein (GP) IIb/IIIa inhibitors and/or stents improve myocardial perfusion
      beyond balloon angioplasty has not been investigated. METHODS: Tissue-level
      perfusion assessed by the myocardial blush grade was evaluated in 1,301 patients
      with AMI randomized to balloon angioplasty versus stenting, each with or without
      abciximab. RESULTS: Despite Thrombolysis In Myocardial Infarction flow grade 3
      restoration in 96.1% of patients, myocardial perfusion was normal in only 17.4%
      of patients, reduced in 33.9%, and absent in 48.7%. Myocardial perfusion status
      post-coronary intervention stratified patients into three distinct risk
      categories, with 1-year mortality rates of 1.4% (normal blush), 4.1% (reduced
      blush), and 6.2% (absent blush) (p = 0.01). Among patients randomized to
      angioplasty, angioplasty + abciximab, stenting, and stenting + abciximab, normal
      myocardial perfusion was restored in 17.7%, 17.0%, 17.5%, and 17.6%, respectively
      (p = 0.95), which was associated with similar 1-year rates of mortality in
      patients randomized to stenting versus angioplasty (4.5% vs. 4.8%, p = 0.91) and
      abciximab versus no abciximab (4.3% vs. 5.0%, p = 0.63). CONCLUSIONS: Restoration
      of normal tissue-level perfusion is a powerful determinate of survival after
      primary PCI in AMI and is achieved in a minority of patients. Neither stents nor
      GP IIb/IIIa inhibitors significantly enhance myocardial perfusion compared to
      balloon angioplasty alone, underlying the similar long-term mortality with these
      different mechanical reperfusion strategies.

PMID- 15261924
TI  - No reflow and the quest to achieve optimal perfusion during the acute phase of
      myocardial infarction.

PMID- 15261925
TI  - Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi formed
      on a collagen surface under blood flow conditions.
AB  - OBJECTIVES: We examined the lytic effects of anti-glycoprotein (GP) IIb/IIIa
      agents on platelet thrombi formed on the collagen surface under blood flow
      conditions. BACKGROUND: Anti-GP IIb/IIIa agents may influence platelet thrombi
      already formed. METHODS: Blood samples were anticoagulated either by the specific
      antithrombin Argatroban (100 microM) or by unfractionated heparin (0.1 U/ml).
      After platelet thrombi were formed on a collagen surface following 6-min
      perfusion of whole blood obtained from eight adult donors containing
      fluorescinated platelets at a wall shear rate of 1,500 s(-1), additional blood
      samples from the same donors either containing or not containing anti-GP IIb/IIIa
      agents (abciximab, eptifibatide, or tirofiban) were perfused on these thrombi.
      The three-dimensional structures of the platelet thrombi were continuously
      observed by laser confocal microscopy equipped with a piezo-electric motor
      control unit and recorded. RESULTS: The platelet thrombi started to dissolve
      after perfusion of blood containing the anti-GP IIb/IIIa agents, whereas their
      growth resumed after subsequent perfusion of control blood. Only a single layer
      of platelets having heights of 3 +/- 1 microm, 3 +/- 2 microm, and 3 +/- 1
      microm, respectively, could be seen after 6-min perfusion of blood containing
      abciximab, eptifibatide, and tirofiban, whereas the initial height of the
      platelet thrombi of 8 +/- 2 microm increased to 11 +/- 4 microm after subsequent
      perfusion of control blood (n = 8). The volume of the platelet thrombi, which was
      3,352 +/- 1,045 microm(3) before starting the second perfusion, was reduced to
      778 +/- 102 microm(3), 812 +/- 122 microm(3), and 856 +/- 144 microm(3) after 6
      min perfusion of blood containing abciximab, eptifibatide, and tirofiban,
      respectively. CONCLUSIONS: We have shown in this study that anti-GP IIb/IIIa
      agents possess the ability to dissolve platelet thrombi.

PMID- 15261926
TI  - Platelet disaggregation: putting time on your side in acute myocardial
      infarction.

PMID- 15261927
TI  - Long-term prognostic significance of left atrial volume in acute myocardial
      infarction.
AB  - OBJECTIVES: The aim of this study was to evaluate the significance of increased
      left atrial (LA) volume determined within the first 48 h of admission as a long
      term predictor of outcome in patients with acute myocardial infarction (MI).
      BACKGROUND: The LA volume reflects left ventricular (LV) diastolic properties.
      Whereas other LV Doppler diastolic characteristics are influenced by acute
      changes in LV function, LA volume is stable and reflects diastolic properties
      before MI. METHODS: Clinical and echocardiographic parameters were prospectively
      collected in 395 consecutive patients with acute MI. Patients with LA volume
      index (LAVI) >32 ml/m(2) (normal + 2 standard deviations) were compared with
      those with LAVI <==32 ml/m(2). Independent clinical and echocardiographic
      prognostic risk factors for five years' mortality were determined by the Cox
      proportional hazard model. RESULTS: Left atrial volume index >32 ml/m(2) was
      found in 63 patients (19%) who had a higher incidence of congestive heart failure
      on admission (24% vs. 12%, p < 0.01), a higher incidence of mitral regurgitation,
      increased LV dimensions, and reduced LV ejection fraction when compared with
      patients with LAVI <==32 ml/m(2). Their five-year mortality rate was 34.5% versus
      14.2% (p < 0.001). Significant independent risk predictors of five years'
      mortality were age (10 years) (odds ratio [OR] 1.45; 95% confidence interval
      [CI]1.14 to 1.86), Killip class >/=2 on admission (OR 2.30; 95% CI 1.29 to 4.09),
      LAVI >32 ml/m(2) (OR 2.22; 95% CI 1.25 to 3.96), diabetes (OR 1.94; 95% CI 1.15
      to 3.28), and LV restrictive filling pattern (OR 1.89; 95% CI 1.09 to 3.31).
      CONCLUSIONS: In patients with acute MI, increased LA volume, determined within
      the first 48 h of admission, is an independent predictor of five-year mortality
      with incremental prognostic information to clinical and echocardiographic data.

PMID- 15261928
TI  - B-type natriuretic peptide at presentation and prognosis in patients with ST
      segment elevation myocardial infarction: an ENTIRE-TIMI-23 substudy.
AB  - OBJECTIVES: We sought to evaluate B-type natriuretic peptide (BNP), alone and in
      comparison to cardiac troponin I (cTnI) and high-sensitivity C-reactive protein
      (hs-CRP), for risk assessment at initial presentation with ST-segment elevation
      myocardial infarction (STEMI). BACKGROUND: Elevated levels of BNP drawn two to
      four days after acute myocardial infarction are associated with higher mortality.
      Sparse data are available on its use at first presentation with STEMI. METHODS:
      We obtained samples from 438 patients presenting within 6 h of STEMI enrolled in
      the Enoxaparin Tenecteplase-Tissue-Type Plasminogen Activator With or Without
      Glycoprotein IIb/IIIa Inhibitor as Reperfusion Strategy in ST-Segment Elevation
      Myocardial Infarction (ENTIRE)-Thrombolysis In Myocardial Infarction (TIMI)-23
      trial. Outcomes were assessed through 30 days. RESULTS: Median BNP was higher in
      patients who died (89 pg/ml, 25th to 75th percentile: 40 to 192), compared with
      survivors (15 pg/ml, 25th to 75th percentile: 8.8 to 32, p < 0.0001). Patients
      with BNP >80 pg/ml were at significantly higher risk of death (17.4% vs. 1.8%, p
      < 0.0001). Cardiac troponin established a gradient of mortality between the
      highest and lowest quartile (7.9% vs. 0%, p = 0.007). C-reactive protein was not
      associated with outcome. After adjustment for cTnI, hs-CRP, and major clinical
      predictors, including age, heart failure, anterior myocardial infarction
      location, heart rate, and blood pressure, a BNP level >80 pg/ml was associated
      with a seven-fold higher mortality risk (odds ratio 7.2, 95% confidence interval
      2.1 to 24.5, p = 0.001). Patients with BNP >80 pg/ml were also more likely to
      have impaired coronary flow (p = 0.049) and incomplete resolution of ST-segment
      elevation (p = 0.05). CONCLUSIONS: Increased concentrations of BNP at initial
      presentation of patients with STEMI are associated with impaired reperfusion
      after fibrinolysis and higher short-term risk of mortality. These data support
      the value of combining markers of hemodynamic stress with traditional approaches
      to risk assessment in acute myocardial infarction.

PMID- 15261929
TI  - Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic
      shock: a report from the SHOCK trial registry.
AB  - OBJECTIVES: We sought to analyze clinical, angiographic, and outcome correlates
      of hemodynamic parameters in cardiogenic shock. BACKGROUND: The significance of
      right heart catheterization in critically ill patients is controversial, despite
      the prognostic importance of the derived measurements. Cardiac power is a novel
      hemodynamic parameter. METHODS: A total of 541 patients with cardiogenic shock
      who were enrolled in the SHould we emergently revascularize Occluded Coronaries
      for cardiogenic shocK (SHOCK) trial registry were included. Cardiac power output
      (CPO) (W) was calculated as mean arterial pressure x cardiac output/451. RESULTS:
      On univariate analysis, CPO, cardiac power index (CPI), cardiac output, cardiac
      index, stroke volume, left ventricular work, left ventricular work index, stroke
      work, mean arterial pressure, systolic and diastolic blood pressure (all p <
      0.001), coronary perfusion pressure (p = 0.002), ejection fraction (p = 0.013),
      and pulmonary artery systolic pressure (p = 0.047) were associated with in
      hospital mortality. In separate multivariate analyses, CPO (odds ratio per 0.20
      W: 0.60 [95% confidence interval, 0.44 to 0.83], p = 0.002; n = 181) and CPI
      (odds ratio per 0.10 W/m(2): 0.65 [95% confidence interval, 0.48 to 0.87], p =
      0.004; n = 178) remained the strongest independent hemodynamic correlates of in
      hospital mortality after adjusting for age and history of hypertension. There was
      an inverse correlation between CPI and age (correlation coefficient: -0.334, p <
      0.001). Women had a lower CPI than men (0.29 +/- 0.11 vs. 0.35 +/- 0.15 W/m(2), p
      = 0.005). After adjusting for age, female gender remained associated with CPI (p
      = 0.032). CONCLUSIONS: Cardiac power is the strongest independent hemodynamic
      correlate of in-hospital mortality in patients with cardiogenic shock. Increasing
      age and female gender are independently associated with lower cardiac power.

PMID- 15261930
TI  - Radial versus femoral approach for percutaneous coronary diagnostic and
      interventional procedures; Systematic overview and meta-analysis of randomized
      trials.
AB  - OBJECTIVES: We sought to compare, through a meta-analytic process, the
      transradial and transfemoral approaches for coronary procedures in terms of
      clinical and procedural outcomes. BACKGROUND: The radial approach has been
      increasingly used as an alternative to femoral access. Several trials have
      compared these two approaches, with inconclusive results. METHODS: The MEDLINE,
      CENTRAL, and conference proceedings from major cardiologic associations were
      searched. Random-effect odds ratios (ORs) for failure of the procedure (crossover
      to different entry site or impossibility to perform the planned procedure), entry
      site complications (major hematoma, vascular surgery, or arteriovenous fistula),
      and major adverse cardiovascular events (MACE), defined as death, myocardial
      infarction, emergency revascularization, or stroke, were computed. RESULTS:
      Twelve randomized trials (n = 3,224) were included in the analysis. The risk of
      MACE was similar for the radial versus femoral approach (OR 0.92, 95% confidence
      interval [CI] 0.57 to 1.48; p = 0.7). Instead, radial access was associated with
      a significantly lower rate of entry site complications (OR 0.20, 95% CI 0.09 to
      0.42; p < 0.0001), even if at the price of a higher rate of procedural failure
      (OR 3.30, 95% CI 1.63 to 6.71; p < 0.001). CONCLUSIONS: The radial approach for
      coronary procedures appears as a safe alternative to femoral access. Moreover,
      radial access virtually eliminates local vascular complications, thanks to a time
      sparing hemostasis technique. However, gaining radial access requires higher
      technical skills, thus yielding an overall lower success rate. Nonetheless, a
      clear ongoing trend toward equalization of the two procedures, in terms of
      procedural success, is evident through the years, probably due to technologic
      progress of materials and increased operator experience.

PMID- 15261931
TI  - Comparison of Mayo Clinic risk score and American College of Cardiology/American
      Heart Association lesion classification in the prediction of adverse
      cardiovascular outcome following percutaneous coronary interventions.
AB  - OBJECTIVES: We compared American College of Cardiology/American Heart Association
      (ACC/AHA) lesion classification with the recently proposed Mayo Clinic risk score
      to predict complications following percutaneous coronary intervention (PCI).
      BACKGROUND: The ability of the ACC/AHA classification system to predict
      complications following PCI has been modest. With the inclusion of patient
      demographics, acuity of presentation, and measure of left ventricular function,
      models with better discriminatory accuracy are presently available. METHODS: The
      Mayo Clinic risk score is constructed by adding integer scores for the presence
      of eight variables. We mapped the lesion-specific risk levels to a patient level
      by counting the number of lesions in each class (A, B1, B2, C, and unknown).
      RESULTS: In 5,064 PCIs, 183 patients (4%) had the primary end point (death, Q
      wave myocardial infarction, stroke, emergency coronary artery bypass graft). Of
      the 7,632 treated lesions, 891 (12%) were unsuccessfully treated with PCI
      (residual stenosis >20%). The discriminatory ability of the Mayo Clinic risk
      score model for prediction of the primary end point, as measured by the c
      statistic, was 0.78 (95% confidence interval [CI] 0.74 to 0.81). The Mayo Clinic
      risk score offered significantly better risk stratification than the ACC/AHA
      lesion classification counts (95% CI for c-statistic difference: 0.05 to 0.15).
      Regarding angiographic success, the ACC/AHA lesion classification was a better
      system (95% CI for c-statistic difference: -0.08 to -0.03 favoring ACC/AHA
      classification), although its absolute ability was modest (c = 0.58).
      CONCLUSIONS: Mayo Clinic risk score offers significantly better prediction for
      cardiovascular complications than the ACC/AHA classification. However, lesion
      classification by ACC/AHA classification is a better predictor for angiographic
      success.

PMID- 15261933
TI  - Potential anti-inflammatory role of activin A in acute coronary syndromes.
AB  - OBJECTIVES: We sought to investigate whether activin A could be involved in the
      immunopathogenesis of acute coronary syndromes. BACKGROUND: Inflammatory
      mechanisms seem to play a pathogenic role in atherosclerosis and acute coronary
      syndromes, but the actual mediators have not been fully identified. Activin A, a
      pleiotropic member of the transforming growth factor-beta cytokine family, has
      recently been suggested to play a role in inflammation. METHODS: We examined the
      role of activin A and its endogenous inhibitor follistatin in patients with
      stable (n = 26) and unstable angina (n = 20) and healthy control subjects (n =
      20) by different experimental approaches. RESULTS: 1) Patients with stable angina
      had raised activin A concentrations, as assessed by protein levels in serum and
      messenger ribonucleic acid levels in peripheral blood mononuclear cells (PBMCs).
      2) Although several activin A-related mediators were upregulated in PBMCs from
      patients with stable angina compared with controls (i.e., activin A and Smad3),
      no changes or even downregulation (i.e., Smad2) were seen in unstable disease. 3)
      The activin type II receptors, representing the primary ligand-binding proteins,
      were downregulated in unstable compared with stable angina. 4) Percutaneous
      coronary intervention induced a decrease in the activin A/follistatin ratio,
      suggesting downregulatory effects on activin A activity. 5) Although activin A
      dose-dependently suppressed the release of inflammatory cytokines from PBMCs in
      angina patients, an opposite effect was found in healthy controls. CONCLUSIONS:
      Our findings suggest an anti-inflammatory potential of activin A in angina
      patients, and such effects may be of particular relevance in unstable angina in
      which several of the activin parameters were downregulated.

PMID- 15261932
TI  - Comparative effects of AT1-antagonism and angiotensin-converting enzyme
      inhibition on markers of inflammation and platelet aggregation in patients with
      coronary artery disease.
AB  - OBJECTIVES: We evaluated whether renin-angiotensin system (RAS) blockade
      attenuates cardiovascular events. BACKGROUND: Because inflammation and enhanced
      thrombogenesis are hallmarks of atherosclerosis, we assessed whether RAS
      inhibition elicits anti-inflammatory and anti-aggregatory effects. METHODS:
      Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP),
      metalloprotease 9 (MMP-9), and interleukin 10 (IL-10) were determined in patients
      with coronary artery disease (CAD) and arterial hypertension six to eight weeks
      after coronary angioplasty (low-density lipoprotein serum levels <150 mg/dl).
      Patients were randomized double-blind to either 20 mg enalapril (ENAL, n = 27) or
      300 mg irbesartan (IRB, n = 21) for 3 months. Blood samples were drawn at
      baseline and at three months. Thromboxane A2-induced platelet aggregation was
      determined turbidimetrically; urine bicyclo-prostaglandin E2 (PGE(2)) and
      inflammatory markers were measured by enzyme-linked immunosorbent assay
      technique. RESULTS: Both treatment regimens enhanced serum IL-10 levels (IRB p <
      0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p <
      0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05). Only IRB reduced serum
      IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas
      ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL). Platelet
      aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p <
      0.001) while urine PGE(2) levels remained unchanged. CONCLUSIONS: Angiotensin
      converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1)
      blockade reduced serum MMP-9 protein/activity to a similar extent, and only AT1
      blockade reduced hsCRP, IL-6, and platelet aggregation in patients with CAD.
      Thus, AT1-blockade appears to exert stronger systemic anti-inflammatory and anti
      aggregatory effects compared with ACE inhibition.

PMID- 15261934
TI  - Is it ever too late to operate on the patient with valvular heart disease?
AB  - All valvular heart disease imparts a hemodynamic burden on the left and/or right
      ventricle. This burden can only be removed effectively by correcting the
      responsible valvular lesion. Although a percutaneous approach is usually used to
      correct mitral stenosis, other valve lesions require surgical intervention. Over
      the past 40 years there has been a persistent improvement in our understanding of
      the pathophysiology of valvular heart disease and in the surgical techniques for
      correcting it. These factors have acted in concert to alter our view of the
      proper timing and applicability of surgery. On one hand it is no longer necessary
      or even advisable to delay surgery until advanced symptoms are present, and thus
      surgery is timed earlier today than it was even a decade ago. On the other hand,
      many but not all patients with far advanced disease, once considered inoperable,
      are now often helped substantially by valve surgery. However, selection of which
      of these very ill patients will or will not benefit from valve surgery remains a
      challenge for all of us. It is this group of patients that is addressed in the
      review.

PMID- 15261935
TI  - Durability of pericardial versus porcine aortic valves.
AB  - OBJECTIVES: This study compares the long-term performance of the Carpentier
      Edwards (CE) porcine bioprosthesis and the CE pericardial bioprosthesis for
      aortic valve replacement (AVR). BACKGROUND: With new bioprostheses on the
      horizon, there is renewed interest in how the long-term durability of current
      pericardial bioprostheses compares with the traditional porcine bioprosthesis.
      METHODS: We reviewed 518 AVR with CE porcine valves from 1974 to 1996 and 1,021
      AVR with CE pericardial valves from 1991 to 2002. The age distribution and
      clinical profiles were similar for both groups. The total (mean) follow-up was
      3,322 (6.4) years for porcine and 2,556 (2.5) years for pericardial. RESULTS:
      Long-term mortality was similar (p = 0.29) for porcine and pericardial, with 10
      year survival rates of 34 +/- 2% and 38 +/- 6%, respectively. Ten-year freedom
      from major adverse cardiac events was also similar for both (respectively):
      thromboembolism (80 +/- 2% and 87 +/- 2%; p = 0.24); endocarditis (98 +/- 1% and
      99 +/- 1%; p = 0.30). However, 10-year freedom from explant was lower for porcine
      (90 +/- 2%) than for pericardial (97 +/- 1%, p = 0.04). Reasons for explant for
      porcine were structural valve deterioration (SVD) (n = 25), endocarditis (n = 4),
      and periprosthetic leak (n = 2). The reasons for explant for pericardial were SVD
      (n = 4), endocarditis (n = 4) and periprosthetic leak (n = 1). CONCLUSIONS: The
      current CE pericardial valve offers better midterm durability than the
      traditional CE porcine valve. Its freedom from SVD and reoperation makes it our
      current bioprosthesis of choice for AVR in appropriately selected patients.

PMID- 15261936
TI  - The choice of valve protheses.

PMID- 15261937
TI  - Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart
      transplantation.
AB  - OBJECTIVES: We studied the outcomes of pediatric patients diagnosed with dilated
      cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic
      variables at the time of presentation. BACKGROUND: The outcome of pediatric DCM
      patients ranges from recovery to a 50% to 60% chance of death within five years
      of diagnosis. The impact of heart transplantation and other emerging therapies on
      the outcomes of pediatric DCM patients is uncertain. METHODS: We performed a
      retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM
      from 1990 to 1999. Routine therapy included use of digoxin, diuretics,
      angiotensin-converting enzyme inhibitors, and heart transplantation. RESULTS: At
      the time of last follow-up, 11 patients (12%) had died without transplantation;
      20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and
      33 (36%) had recovery of left ventricular systolic function. Overall actuarial
      one-year survival was 90%, and five-year survival was 83%. However, actuarial
      freedom from "heart death" (death or transplantation) was only 70% at one year
      and 58% at five years. Multivariate analysis found age <1 year (hazard ratio
      7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to
      be significantly associated with a greater risk of death or transplantation and a
      higher left ventricular shortening fraction at presentation (hazard ratio 0.92),
      with a slightly decreased risk of death or transplantation. CONCLUSIONS:
      Pediatric DCM patients continue to have multiple outcomes, with recovery of left
      ventricular systolic function occurring most frequently. Utilization of heart
      transplantation has led to improved survival after the diagnosis of pediatric
      DCM.

PMID- 15261938
TI  - Progressive left ventricular remodeling in patients with hypertrophic
      cardiomyopathy and severe left ventricular hypertrophy.
AB  - OBJECTIVES: The aim of this study was to determine the natural history of
      patients with hypertrophic cardiomyopathy (HCM) and severe left ventricular
      hypertrophy (LVH) (i.e., maximal left ventricular wall thickness [MLVWT] >/=30
      mm) and whether changes in cardiac morphology influence the course of the
      disease. BACKGROUND: Severe LVH is common in young and rare among elderly
      patients with HCM. This has been explained by a high incidence of sudden death.
      We hypothesized that this age-related difference might be explained by left
      ventricular wall thinning. METHODS: A total of 106 (age 33 +/- 15 years; 71
      males) consecutive patients with severe LVH underwent history taking,
      examination, electrocardiography, echocardiography, cardiopulmonary exercise
      testing, and Holter analysis. Survival data were collected at subsequent clinic
      visits or by communication with patients and their general practioners. In order
      to assess morphologic and functional changes, 71 (67.0%) patients (mean age 31 +/
      15 years; 47 males) followed at our institution underwent serial (>/=1 year)
      assessment. RESULTS: Of the 106 patients, the majority (78 [71.6%]) were <40
      years of age. During follow-up (92 +/- 50 months [range 1 to 169]), 18 (17.0%)
      patients died or underwent heart transplantation (13 sudden cardiac deaths, 2
      heart failure deaths, 1 heart transplantation, 1 stroke, 1 postoperative death).
      Five-year survival from sudden death was 90.1% (95% confidence interval [CI]
      84.0% to 96.3%), and that from heart failure death or transplantation was 97.7%
      (95% CI 94.5 to 100). In patients serially evaluated over 85 +/- 51 months, there
      was an overall reduction in MLVWT of 0.6 mm/year (95% CI 0.31 to 0.81, p =
      0.00004). Wall thinning >/=5 mm was observed in 41 patients (57.7%; age 35 +/- 13
      years; 28 males). On multivariate analysis, the follow-up duration only predicted
      wall thinning (0.6 mm/year, 95% CI 0.38 to 0.85, p < 0.00001). CONCLUSIONS: Left
      ventricular remodeling is common in patients with severe LVH and contributes to
      the low prevalence of severe LVH seen in middle age and beyond.

PMID- 15261939
TI  - Left ventricular hypertrophy in hypertrophic cardiomyopathy: what's in a
      phenotype?

PMID- 15261940
TI  - Importance of ablating all potential right atrial flutter circuits in postcardiac
      surgery patients.
AB  - OBJECTIVES: In patients with atrial flutter (AFL) and postoperative right atrial
      incisional scars, we sought to assess if the use of additional ablative lesions
      that targeted all potential re-entrant circuits, regardless of the presenting
      type of flutter, would prevent long-term recurrence. BACKGROUND: Patients with
      AFL and incisional scars have a complex atrial substrate that may promote
      multiple mechanisms of intra-atrial re-entry. METHODS: Twenty-nine patients with
      single right atrial incisional scars undergoing ablation for scar-dependent (n =
      15) and cavotricuspid isthmus (CTI)-dependent (n = 14) flutter were studied.
      RESULTS: In the scar-dependent group, 9 of 15 (60%) patients had inducible or
      spontaneous CTI-dependent flutter immediately after ablation. In the group with
      CTI flutter, 7 of 14 (50%) patients had scar-related flutter immediately after
      ablation. If a second type of flutter was found during the initial ablation, a
      second ablation was performed either along the isthmus (scar-dependent group) or
      from the scar to another anatomic boundary (isthmus-dependent group). Patients
      were followed for 24 +/- 5 months and 18 +/- 6 months in the scar- and CTI
      dependent groups, respectively. In the scar-dependent group, five of six (83%)
      who underwent only a single flutter line had recurrence at 3 +/- 1 months. In the
      isthmus-dependent group, three of seven (42%) patients who had only one flutter
      line performed had recurrence at 5 +/- 3 months. There was no flutter recurrence
      in patients who initially received two different flutter lines or in patients who
      subsequently underwent a second flutter line at follow-up. CONCLUSIONS: In
      patients with postoperative right atrial incisional scar and flutter, multiple
      ablation lines that target both scar-related and classic isthmuses appear
      necessary to prevent long-term recurrence.

PMID- 15261941
TI  - Platelet indexes in relation to target organ damage in high-risk hypertensive
      patients: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).
AB  - OBJECTIVES: We sought to investigate the relationship between target organ damage
      (TOD) in hypertension and a prothrombotic/hypercoagulable state, using a new
      technique of "platelet lysis" to quantify the amount of P-selectin per platelet
      (pP-sel), and to correlate it with other platelet markers (e.g., mass, volume and
      granularity, soluble P-selectin [sP-sel], and beta-thromboglobulin [beta-TG]).
      BACKGROUND: The increased risk of TOD in hypertension may be related to a
      prothrombotic/hypercoagulable state, with abnormalities in platelets, such as
      increased expression of P-selectin. METHODS: We studied 199 patients (mean age 68
      years, 75% men) with hypertension. Of these, 125 had TOD (e.g., stroke, previous
      myocardial infarction, angina, left ventricular hypertrophy). Values obtained
      were compared with those from 59 healthy normotensive control subjects (mean age
      68 years, 58% men). RESULTS: Hypertensive patients had a higher mean platelet
      volume, mass, pP-sel, sP-sel, and beta-TG and lower platelet granularity (all p <
      0.01), but a similar platelet count, as compared with controls. Within the
      hypertensive group, those with evidence of TOD had significantly larger platelets
      with greater mass but had lower granularity, sP-sel, and pP-sel levels than those
      without TOD, possibly reflecting increased aspirin use. On multivariate analysis,
      aspirin use was a determinant of pP-sel (p = 0.03) and sP-sel (p = 0.01), but the
      use of other drugs or other co-morbidity (e.g., diabetes, smoking) did not
      influence either P-selectin value. CONCLUSIONS: Patients with hypertension have
      evidence of changes in platelet physiology, as reflected by a higher level of pP
      sel. Patients with TOD also had larger platelets, with greater mass, and the use
      of aspirin lowered pP-sel and sP-sel levels. These changes may have implications
      for the pathophysiology of cardiovascular and cerebrovascular disease in
      hypertension.

PMID- 15261942
TI  - The incremental prognostic value of percentage of heart rate reserve achieved
      over myocardial perfusion single-photon emission computed tomography in the
      prediction of cardiac death and all-cause mortality: superiority over 85% of
      maximal age-predicted heart rate.
AB  - OBJECTIVES: We sought to determine whether chronotropic incompetence (CI) adds
      incremental value in predicting cardiac death (CD) and all-cause mortality and to
      determine which marker of CI is superior. BACKGROUND: Chronotropic incompetence,
      defined by either a low percent heart rate (HR) reserve achieved or failure to
      achieve 85% maximal age-predicted heart rate (MA-PHR), is a predictor of
      mortality. These variables have not been examined together in a comprehensive
      myocardial perfusion single-photon emission computed tomographic (SPECT), or MPS,
      model. METHODS: A total of 10,021 patients who underwent exercise MPS, evaluated
      by a summed stress score (SSS), were followed up for 719 +/- 252 days. Percent HR
      reserve = (peak HR - rest HR)/(220 - age - rest HR) x 100, with <80% considered
      abnormal. RESULTS: A total of 2,956 patients (29.5%) had low %HR reserve; 1,331
      (13.3%) achieved <85% MA-PHR; and 1,296 (13.0%) had both. There were 234 deaths
      (93 CDs). On multivariate analysis, the SSS, %HR reserve, and inability to
      achieve 85% MA-PHR were predictors of all-cause mortality and CD (all p < 0.01).
      Myocardial perfusion SPECT was the most powerful predictor of CD (chi-square =
      50). When the %HR reserve and ability to achieve 85% MA-PHR were considered, only
      the former remained a predictor of CD (p = 0.006 vs. p = 0.59). CONCLUSIONS: In a
      comprehensive MPS model, CI was an important predictor of CD and all-cause
      mortality. Percent HR reserve was superior to the ability to achieve 85% MA-PHR
      in predicting CD; MPS was superior to both. Combined with previous studies, the
      findings suggest that %HR reserve should become the standard for assessing the
      adequacy of HR response during exercise testing, and that it should be routinely
      incorporated in risk stratification algorithms.

PMID- 15261943
TI  - Chronotropic incompetence: ready for prime time.

PMID- 15261944
TI  - Impact of pregnancy on the systemic right ventricle after a Mustard operation for
      transposition of the great arteries.
AB  - OBJECTIVES: We sought to determine the impact of pregnancy on the systemic right
      ventricle (RV) after a Mustard operation for transposition of the great arteries.
      BACKGROUND: Dysfunction of the RV remains a continuing problem after a Mustard
      operation. Concerns exist about the potentially deleterious effects of pregnancy
      on this ventricle. METHODS: The records of 16 women who completed 28 pregnancies
      were reviewed for clinical status, echocardiographic evaluation of RV dimensions,
      RV function, and tricuspid regurgitation (TR) before, during, and after
      pregnancy. RESULTS: Women were in New York Heart Association functional class I
      (n = 21) and II (n = 7) before pregnancy. The functional class deteriorated in
      six women, with no return to the pre-pregnancy level after delivery in two. Data
      on RV dimensions were available in 18 pregnancies, on RV function in 21, and on
      TR in 20. Before pregnancy, RV dilation was absent (n = 4), mild/moderate (n =
      12), or severe (n = 2) and progressed in five women (31%), with no recovery in
      all patients at the last follow-up. Right ventricular systolic dysfunction was
      absent (n = 16), mild/moderate (n = 4), or severe (n = 1) before pregnancy and
      progressed in four women (25%), with no recovery in three cases. Tricuspid
      regurgitation was absent (n = 8), mild (n = 9), or moderate (n = 3) before
      pregnancy and deteriorated in eight women (50%), with no recovery in three
      patients. CONCLUSIONS: Pregnancy after a Mustard operation is clinically well
      tolerated but carries a risk of RV dysfunction, which is sometimes irreversible.

PMID- 15261945
TI  - Initial results and medium-term follow-up of stent implantation of patent ductus
      arteriosus in duct-dependent pulmonary circulation.
AB  - OBJECTIVES: This study was designed to assess the safety, efficacy, medium-term
      outcome, and complications of patent ductus arteriosus (PDA) stenting in duct
      dependent pulmonary circulation. BACKGROUND: Patent ductus arteriosus stenting
      has been proposed as an alternative to surgical shunt on account of postoperative
      morbidity and complications of surgical shunting. METHODS: Between April 2000 and
      February 2003, 69 patients with duct-dependent pulmonary circulation underwent
      cardiac catheterization with the intent of PDA stenting as first palliative
      procedure. Patients with critical pulmonary stenosis and pulmonary atresia with
      intact ventricular septum post-radiofrequency valvotomy who had PDA stenting were
      excluded. Thirteen more patients were excluded because of branch pulmonary artery
      (PA) stenosis. The follow-up was by clinical examination, echocardiography, and
      repeat cardiac catheterization at six to nine months following the procedure.
      RESULTS: Patent ductus arteriosus stenting was successful in 51 patients (91.1%)
      and failed in 5 patients (8.9%). The mean narrowest PDA diameter was 1.9 +/- 0.6
      mm. The mean procedure and fluoroscopy time were 95.7 min and 29.4 min,
      respectively. In one patient the stent dislodged and migrated to the left femoral
      artery and another patient developed transient intravascular hemolysis. There was
      no procedure-related mortality. Three patients (5.9%) died one day to two months
      after the procedure. At follow-up (3.2 months to 2.4 years), 8 patients developed
      significant stent stenosis requiring reintervention. Seven patients developed
      worsening of preexisting branch PA stenosis. The freedom from reintervention was
      89% and 55% at 6 months and 1 year, respectively. CONCLUSIONS: Patent ductus
      arteriosus stenting is an attractive alternative to surgical shunt in a majority
      of patients with duct-dependent circulation. An absolute contraindication to this
      technique is the presence of branch pulmonary stenosis.

PMID- 15261946
TI  - Aortico-left ventricular tunnel: 35-year experience.
AB  - OBJECTIVES: The purpose of this study was to review our 35 years of experience
      with aortico-left ventricular tunnel (ALVT), with emphasis on diagnosis, surgical
      details, and follow-up. BACKGROUND: Aortico-left ventricular tunnel is a rare
      congenital anomaly. Neonatal surgery has been advocated in all due to long-term
      concern of valvar aortic regurgitation (AR). METHODS: We identified 11 patients
      from 1963 to August 2002. Clinical, echocardiographic, catheterization, and
      surgical details were reviewed. RESULTS: Eight of 11 patients presented at less
      than six months old (six with congestive heart failure) and three later with a
      murmur, all with clinical evidence of AR. Associated lesions, most commonly
      aortic valve and coronary artery anomalies, were present in 45%. Catheter
      occlusion was considered but not performed in five. Spontaneous occlusion was
      documented in one. Ten had surgery (nine in our institution), seven with direct
      suture and two by patch closure of the aortic end of the AVLT. At follow-up
      (median, 5 years; 1 month to 35 years), all were asymptomatic; three had residual
      ALVT (one moderate, two small/trivial), with at most mild AR. CONCLUSIONS:
      Aortico-left ventricular tunnel is a rare cardiac malformation with a good post
      operative long-term outcome. Associated lesions occurred in 45%. Catheterization
      should be reserved for patients with unclear non-invasive findings or
      transcatheter closure. We recommend surgery for most patients. We report
      spontaneous closure in one patient, prompting consideration of conservative
      follow-up in rare small, asymptomatic AVLT.

PMID- 15261947
TI  - Plasma level of oxidized low-density lipoprotein is an independent determinant of
      coronary macrovasomotor and microvasomotor responses induced by bradykinin.
AB  - OBJECTIVES: We examined the relationship between coronary endothelium-dependent
      vasodilation in response to bradykinin (BK) and plasma levels of oxidized low
      density lipoprotein (oxLDL) in subjects with normal coronary arteries.
      BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of
      coronary endothelial function. Bradykinin plays an important role in regulating
      resting coronary tone and flow-mediated coronary vasomotion. METHODS: Coronary
      blood flow (CBF) in the left anterior descending (LAD) coronary artery was
      assessed by quantitative angiography and a Doppler flow wire in 94 consecutive
      subjects with normal coronary arteries. The plasma oxLDL level was measured by
      enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL.
      RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than
      those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with
      body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 microg/min caused
      dose-dependent increases in diameter and CBF in the LAD coronary artery. By a
      univariate analysis, oxLDL levels significantly correlated with epicardial (r = 
      0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator
      responses to BK at 2.0 microg/min, whereas total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides
      were not associated with these coronary responses. In a stepwise multivariate
      analysis, oxLDL levels were significantly correlated with epicardial and
      resistant coronary vasomotor responses to BK, independent of age, gender, smoking
      status, other lipid levels, BMI, hypertension, and diabetes. CONCLUSIONS: The
      plasma level of oxLDL is an appropriate surrogate for assessing coronary
      endothelial-dependent vasomotor function as estimated by responses to BK compared
      with conventional risk factors for atherosclerosis.

PMID- 15261948
TI  - Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors
      for the repair of infarcted myocardium.
AB  - OBJECTIVES: The present study was designed as a face-to-face functional
      comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived
      hematopoietic progenitors in an animal model of semichronic myocardial
      infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the
      advantage of plasticity and might more effectively regenerate ischemic cardiac
      tissue. However, few data exist on the comparative efficacy of these two cell
      types in semichronic infarcts. METHODS: A myocardial infarction was created by
      coronary ligation in 32 nude rats. Ten days later, rats received in-scar
      injections of human SMs, CD133(+) progenitors, or culture medium. Left
      ventricular function was assessed before and one month after transplantation by
      echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain
      reaction, and in situ hybridization were used to detect cells grafted in the
      hearts. RESULTS: One month after transplantation, left ventricular ejection
      fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in
      CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM
      treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure
      volume loops paralleled these data. Engrafted myotubes were identified in all SM
      treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few
      human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the
      setting of postinfarction scars, the transplantation of bone marrow-derived
      CD133(+) progenitors improves cardiac function, but this benefit is not superior
      to that afforded by myogenic cells.

PMID- 15261949
TI  - Wanted! The best cell for cardiac regeneration.

PMID- 15261951
TI  - Definition of physiological hypertrophy in ultramarathon athletes.

PMID- 15261952
TI  - Echocardiographic limits of left ventricular remodeling in athletes.

PMID- 15261953
TI  - Suggested new upper limit of physiologic cardiac hypertrophy determined in
      Japanese ultramarathon runners must be interpreted cautiously.

PMID- 15261955
TI  - Depression as a risk factor for post-MI mortality.

PMID- 15261956
TI  - Is depression a risk factor for coronary heart disease?

PMID- 15261958
TI  - ACC/AHA key data elements and definitions for measuring the clinical management
      and outcomes of patients with atrial fibrillation: A report of the American
      College of Cardiology/American Heart Association Task Force on Clinical Data
      Standards (Writing Commitee to Develop Data Standards on Atrial Fibrillation).

PMID- 15261959
TI  - Passiflora: a review update.
AB  - This review describes the morphology, microscopy, traditional and folklore uses,
      phyto-constituents, pharmacological reports, clinical applications and
      toxicological reports of the prominent species of the genus Passiflora.
      Flavonoids, glycosides, alkaloids, phenolic compounds and volatile constituents
      have been reported as the major phyto-constituents of the Passiflora species. A
      few species of Passiflora have been used for curing various ailments, the most
      important being Passiflora incarnata Linneaus which possesses significant CNS
      depressant properties. The studies performed by the authors with the newly
      isolated benzoflavone (BZF) moiety from P. incarnata have been discussed. In the
      concluding part, various virgin areas of research on the species of this genus
      have been highlighted with a view to explore, isolate and identify the
      medicinally important phyto-constituents which could be utilized to alleviate
      various diseases affecting the mankind.

PMID- 15261960
TI  - Safety evaluation of neem (Azadirachta indica) derived pesticides.
AB  - The neem tree, Azadirachta indica, provides many useful compounds that are used
      as pesticides and could be applied to protect stored seeds against insects.
      However in addition to possible beneficial health effects, such as blood sugar
      lowering properties, anti-parasitic, anti-inflammatory, anti-ulcer and
      hepatoprotective effects, also toxic effects are described. In this study we
      present a review of the toxicological data from human and animal studies with
      oral administration of different neem-based preparations. The non-aqueous
      extracts appear to be the most toxic neem-based products, with an estimated safe
      dose (ESD) of 0.002 and 12.5 microg/kg bw/day. Less toxic are the unprocessed
      materials seed oil and the aqueous extracts (ESD 0.26 and 0.3 mg/kg bw/day, 2
      microl/kg bw/day respectively). Most of the pure compounds show a relatively low
      toxicity (ESD azadirachtin 15 mg/kg bw/day). For all preparations, reversible
      effect on reproduction of both male and female mammals seem to be the most
      important toxic effects upon sub-acute or chronic exposure. From the available
      data, safety assessments for the various neem-derived preparations were made and
      the outcomes are compared to the ingestion of residues on food treated with neem
      preparations as insecticides. This leads to the conclusion that, if applied with
      care, use of neem derived pesticides as an insecticide should not be discouraged.

PMID- 15261961
TI  - The constituents of essential oil and in vitro antimicrobial activity of
      Micromeria cilicica from Turkey.
AB  - The chemical composition of the essential oil of Micromeria cilicica (Labiatae)
      that has been used in folk medicine were analysed by GC, GC-MS, 1H NMR and 13C
      NMR. The totals of 34 components in hydrodistillation, 30 components in steam
      distillation were detected. The major component characterized in the essential
      oils was pulegone (66.55, 64.10%) and other main components were determined as
      cis-p-menthone (21.71, 25.31%), trans-p-menthone (9.59, 5.59%), nerol (0.35,
      2.49%) and 3-octonol (0.81, 0.25%), respectively. Essential oils obtained by
      hydro and steam distillation and organic solvent extracts of the aerial parts of
      the plant were investigated for antimicrobial activities on several
      microorganisms including bacteria and yeast. Moreover, the main constituent of
      the oil has been tested against the same microorganisms. The extracts and
      pulegone exhibited a significant antibacterial and antifungal activity. The
      activities were increased depend on the amount of extracts and pulegone. Pulegone
      also showed antimicrobial activity, particularly against Candida albicans and
      Salmonella typhimurium. Furthermore Candida albicans is the most susceptible to
      pulegone giving two times the effect of nystatin.

PMID- 15261962
TI  - Effective medicinal plants against enterohaemorrhagic Escherichia coli O157:H7.
AB  - The stimulating effect of subinhibitory concentrations of antibiotics on the
      production of verocytotoxin (VT) by enterohaemorrhagic Escherichia coli (EHEC)
      O157:H7 has been claimed. The purpose of this study was to find an alternative,
      but bioactive medicine for the treatment of this organism. Fifty-eight
      preparations of aqueous and ethanolic extracts of 38 medicinal plant species
      commonly used in Thailand to cure gastrointestinal infections were tested for
      their antibacterial activity against different strains of Escherichia coli,
      including 6 strains of Escherichia coli O157:H7, Escherichia coli O26:H11,
      Escherichia coli O111:NM, Escherichia coli O22; 5 strains of Escherichia coli
      isolated from bovine; and Escherichia coli ATCC 25922. Inhibition of growth was
      primarily tested by the paper disc agar diffusion method. Among the medicinal
      plants tested, only 8 species (21.05%) exhibited antimicrobial activity against
      Escherichia coli O157:H7. Acacia catechu, Holarrhena antidysenterica, Peltophorum
      pterocarpum, Psidium guajava, Punica granatum, Quercus infectoria, Uncaria
      gambir, and Walsura robusta demonstrated antibacterial activity with inhibition
      zones ranging from 7 to 17 mm. The greatest inhibition zone against Escherichia
      coli O157:H7 (RIMD 05091083) was produced from the ethanolic extract of Quercus
      infectoria. Minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) were determined by the agar microdilution method and agar
      dilution method in petri dishes with millipore filter. Both aqueous and ethanolic
      extracts of Quercus infectoria and aqueous extract of Punica granatum were highly
      effective against Escherichia coli O157:H7 with the best MIC and MBC values of
      0.09, 0.78, and 0.19, 0.39 mg/ml, respectively. These plant species may provide
      alternative but bioactive medicines for the treatment of Escherichia coli O157:H7
      infection.

PMID- 15261963
TI  - Antiulcerogenic effects of Campomanesia xanthocarpa.
AB  - Campomanesia xanthocarpa O. Berg., popularly known as "gabiroba", is used in
      Brazilian folk medicine for ulcer treatment. The hydroalcoholic extract of
      Campomanesia xanthocarpa leaves was evaluated for antiulcerogenic activity, acute
      toxicity and phytochemical profile. Oral administration of the extract at 400
      mg/kg proved to be effective in preventing gastric ulceration in rats and did not
      produce toxic symptoms in mice in doses up to 5 g/kg. TLC screening methods
      revealed the presence of flavonoids, saponins and tannins.

PMID- 15261964
TI  - Effect of Brazilian green propolis on the production of reactive oxygen species
      by stimulated neutrophils.
AB  - The activity of a crude ethanol extract of green propolis and its fractions
      obtained by partition with hexane, chloroform and n-butanol was assessed on
      luminol- and lucigenin- enhanced chemiluminescence (CL) produced by rabbit
      neutrophils (PMNs) stimulated with particles of serum-opsonized zymosan (OZ). The
      total production of reactive oxygen species (ROS) by PMNs was measured by the
      luminol-enhanced CL (LumCL) assay and the production of the superoxide anion (O2*
      ) by the lucigenin-enhanced CL (LucCL) assay. All evaluated propolis samples had
      inhibitory effect on the LumCL and LucCL, which was concentration dependent. The
      n-butanol and chloroform fractions displayed the highest inhibitory effect on the
      LumCL produced by PMNs stimulated with OZ, in comparison with both the ethanol
      extract and the hexane fraction. Besides, the hexane fraction was the one which
      presented the highest effect for the LucCL assay. Some isolated compounds from
      both n-butanol and chloroform fractions were also assessed, including
      kaempferide, isosakuranetin, aromadendrine-4'-methyl-ether and 3-prenyl-p
      coumaric acid. Kaempferide presented the highest inhibitory effect on the LumCL
      in comparison with the other compounds. Moreover, under the conditions assessed,
      the studied green propolis samples and isolated compounds were not toxic to the
      rabbit PMNs.

PMID- 15261965
TI  - Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich
      in superoxide dismutase activity.
AB  - The present study was conducted to evaluate in vitro and in vivo the antioxidant
      and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC.,
      Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity.
      Peritoneal macrophages were pre-activated in vitro with 300 IU of interferon
      gamma (IFN-gamma) and were then challenged in culture with IgGl/anti-IgG1 immune
      complexes (IgG1IC) in presence of various CME extracts. The subsequent production
      of free radicals (superoxide anion, nitric oxide, and peroxynitrite) and of pro
      (TNF-alpha) and anti-(IL-10) inflammatory cytokines was evaluated. The CME
      inhibited in a dose-dependent manner the production of superoxide anion with a
      maximal effect at 100 microg/ml. This inhibitory effect of CME appeared to be
      closely linked to the SOD activity because it was dramatically decreased after
      heat inactivation of the SOD activity (HI-CME). In addition, the CME inhibited
      the production of peroxynitrite strengthening the antioxidant properties of this
      CME rich in SOD activity. The production of the pro- and anti-inflammatory
      cytokines, namely TNF-alpha and IL-10, being conditioned by the redox status of
      macrophages we also evaluated the effect of CME and HI-CME on the IgG1IC-induced
      cytokine production. When the SOD activity was present in the CME it promoted the
      IgG1IC-induced production of IL-10 instead of TNF-alpha. These data demonstrated
      that, in addition to its antioxidant properties, the anti-inflammatory properties
      of the CME extract were principally related to its capacity to induce the
      production of IL-10 by peritoneal macrophages. The particular properties of wheat
      gliadin (Triticum vulgare, Poaceae) for the oral delivery of functional proteins
      led us to test it in a new nutraceutical formula based on its combination with
      the CME thus monitoring the SOD activity release during the gastro-intestinal
      digestive process. In these experiments C57BL/6 mice were supplemented orally
      everyday during 28 days with: (1) the placebo, (2) the CME extract alone, (3) the
      gliadin, (4) the CME/gliadin combination, or (5) the HI-CME/gliadin combination
      (SOD inactivated). At the end of the supplementation period all the animals were
      injected intra-peritoneal (i.p.) with the pro-inflammatory cytokine IFN-gamma
      (300 IU) and peritoneal macrophages were harvested 24 h after to test their
      capacities to produce free radicals, TNF-alpha and IL-10 after triggering with
      IgG1IC. We demonstrated that animals supplemented during 28 days with the
      CME/gliadin combination were protected against the pro-inflammatory properties of
      IFN-gamma while the other products were inefficient. These data did not only
      indicate that the SOD activity is important for the antioxidant and anti
      inflammatory properties of the CME extract, but also demonstrated that when the
      SOD activity is preserved during the digestive process by its combination with
      wheat gliadin it is possible to elicit in vivo the pharmacological effects of
      this antioxidant enzyme.

PMID- 15261966
TI  - Evaluation of sedative and anticonvulsant activities of Unmadnashak Ghrita.
AB  - 'Unmadnashak Ghrita' (UG) is a ayurvedic formulation containing Ferula narthex (6
      g), Gardenia gummifera (6 g), Ellataria cardamom (6 g), Bacopa monneri (6 g), and
      cow's ghee (clarified butter fat) (76 g). In the present study,
      neuropharmacological activities of UG were evaluated for its gross behavioural
      effect, pentobarbitone sleeping time, spontaneous locomotor activity, antagonism
      to amphetamine induced hyperlocomotor activity, analgesic activity by tail flick
      test, rota-rod performance (motor coordination test), maximal electroshock (MES)
      induced seizures, and pentylenetetrazol (PTZ) induced convulsions in mice. The
      formulation showed CNS-depressant activity in gross behavioural test, potentiated
      pentobarbitone sleeping time and there was significant decrease in spontaneous
      locomotor count in mice. The formulation also antagonized the behavioral effects
      of CNS-stimulant drug amphetamine, and showed analgesic effect in mice. UG failed
      to affect the motor coordination test. The formulation also protected mice from
      MES and PTZ induced convulsions. These results suggest that UG has CNS-depressant
      and anticonvulsant activity in mice.

PMID- 15261967
TI  - Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula
      in penile tissues of aged and diabetic rats.
AB  - We investigated the mechanisms underlying the effects of an herbal formula (HF)
      in improving erectile dysfunction (ED), particularly in terms of nitric oxide
      (NO)-cGMP pathways. Two different rat models, 24-month-old rats (aging) and 10
      month-old rats maintained chronically high plasma glucose levels (328 +/- 89
      mg/dL) diabetes mellitus (DM), were treated with HF (100 mg/kg per day) for 10
      days. We examined the electrostimulated penile responses, expression and activity
      of three enzymes: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS) and
      caveolin-1 (CaV-1), and cGMP concentration that act upon the major NO-cGMP
      signaling pathways in penile tissue. Effect of HF on cGMP degradation was also
      examined using bovine vascular smooth-muscle cells pretreated with an NO donor, S
      nitroso-N-acetylpenicillamine (SNAP). In aging and DM rats, the severely reduced
      peak intracavernous pressures (ICPs) in penile tissues were restored completely
      after HF treatment, and HF treatment significantly made the latency period
      earlier. Furthermore, the penile expression levels of nNOS, eNOS and CaV-1, Ca2+ 
      dependent NOS activities and cGMP concentrations were increased significantly in
      the HF-treated rats. Particularly, inhibitory effect of HF on cGMP degradation
      was confirmed also in cell system. These results indicate that new HF originated
      from a Korean traditional medicine (Ojayounjonghwon described in 'Dong Ui Bo
      Gam') can ameliorate the ED impaired by peripheral neuropathy and/or angiopathy,
      via the activation of NO-cGMP pathways.

PMID- 15261968
TI  - Evaluation of antinociceptive, anti-inflammatory and antiulcerogenic activities
      of Maytenus ilicifolia.
AB  - Maytenus ilicifolia (Celastraceae) is a native plant from Tropical Atlantic
      Forest (Mata Atlantica, Brazil) called 'espinheira-santa'. This plant is
      traditionally used as anti-inflammatory, analgesic and antiulcerogenic. Many
      studies focusing pharmacological and toxicological aspects of the plant have been
      performed. The aim of this study is to evaluate the efficacy (anti-inflammatory
      and antinociceptive activities and protection against gastric lesions, including
      cytoprotection and healing) and phytochemical profile of hexane and ethylacetate
      extracts of Maytenus ilicifolia. Per os administration of these extracts
      inhibited nociception and formaldehyde-induced paw oedema in mice and carrageenin
      induced paw oedema in rats. Severity of gastric lesions induced by cold-restraint
      stress (-18 degrees C for 45 min) method was also clearly reduced in rats
      considering both cytoprotection and healing aspects. Administration of the
      extracts led to volume gastric and pH increase. These results suggest that hexane
      and ethylacetate extracts of Maytenus ilicifolia may represent an important
      clinical alternative in anti-inflammatory and antiulcerogenic therapeutics,
      though, further experiments should be performed to confirm this assertion.

PMID- 15261969
TI  - Protective effect of total flavones from Elsholtzia blanda (TFEB) on myocardial
      ischemia induced by coronary occlusion in canines.
AB  - This study was undertaken to determine the effect of total flavones from
      Elsholtzia blanda (Benth.) Benth. (TFEB), a traditional Chinese medicine, on
      myocardial ischemia induced by coronary occlusion in Beagle dogs. Infarct size of
      left ventricle, serum activity of creatine kinase-MB (CK-MB) and malondialdehyde
      (MDA), hemorrheologic variables and homodynamic parameters including mean
      arterial pressure (MAP), coronary blood flow (CBF), coronary vascular resistance
      (CVR), end-diastolic pressure of left ventricle (LVEDP), rate of rise and decline
      of left ventricular pressure (+/-dp/dtmax) were measured in this study.
      Administration with TFEB produced a dose-dependent reduction in infarct size.
      TFEB 100 mg/kg exerted notable inhibition in the elevation of serum CK-MB and MDA
      activity. TFEB significantly reduced MAP and CVR. The decrease in CBF also tended
      to be smaller in treated dogs. TFEB improved the recovery of myocardial function
      by depressing the degree of reduction in +/-dp/dtmax and LVEDP. TFEB also showed
      a capacity to resist ischemic damage through lowering blood viscosity. The
      results indicated that TFEB kept heart from ischemic damage due to coronary
      occlusion in Beagle dogs.

PMID- 15261970
TI  - Phoradendron liga (Gill. ex H. et A.) Eichl. (Viscaceae) used in folk medicine:
      anatomical, phytochemical, and immunochemical studies.
AB  - Phoradendron liga (Gill. ex H. et A.) Eichl. is a Viscaceae widely distributed in
      Argentina. It has been commonly used in folk medicine as a substitute of the
      European mistletoe (Viscum album L.) to decrease high blood pressure due to their
      external similarity. In this study, the anatomical features as well as
      micromolecular and macromolecular analysis of this species are reported.
      Anatomical study has shown that Phoradendron liga presents as anatomic features:
      papillous cuticle, clusters in leaves and stems, and isodiametric stone cells
      only in stems. The analysis of flavonoids showed that this species produces C
      glycosylflavones and 3-desoxyproanthocyanidins. Protein study showed a protein
      pattern with components ranging from 14 to 90 kDa and the presence of related
      epitopes between the species was demonstrated by cross recognition using anti
      Phoradendron and anti-Viscum antisera of both species by Western blot assay. In
      addition, a galactose specific lectin (L-Phl) was isolated form Phoradendron liga
      extracts. These results are part of a comprehensive project on Argentine
      hemiparasite species destinated to be applied to quality control of commercial
      samples and disclosed their potential use as a potential source for
      immunomodulatory compounds.

PMID- 15261971
TI  - Anticancer and antiviral activities of Youngia japonica (L.) DC (Asteraceae,
      Compositae).
AB  - Aqueous and ethanol extracts of Youngia japonica (also known as Oriental
      hawksbeard) were tested in vitro for anti-tumor activity against three cell
      lines, human promyelocytic leukaemia (HL-60), human myelogenous leukaemia
      (chronic K-562) and mouse Sarcoma 180 (S-180), and for antiviral activity against
      respiratory syncytial virus (RSV), influenza A virus (Flu A) and herpes simplex
      virus type 1 (HSV-1) by cytopathic effect (CPE) reduction assay. Hot water
      extract of Youngia japonica inhibited cell proliferation and growth of all cancer
      cell lines to various extent. K-562 cells were the most sensitive to the extract
      whereas S-180 cells were the least. It did not show any significant cytotoxic
      effects on normal mammalian Vero cells up to the concentration of 450 microg/mL.
      The ethanol extract of whole plant of Youngia japonica exhibited antiviral
      activity against RSV cultured in HEp-2 cells, but did not have any activity
      against Flu A and HSV-1. Two partially purified fractions (Fr.10 and Fr.11) from
      the 95% ethanol extract exhibited significant anti-RSV with 50% inhibitory
      concentration (IC50) in the range of 3.0-6.0 microg/mL. The ratio of the viral
      titer reduction in the absence (viral control) and presence of the maximal non
      cytotoxic concentration (MNCC) of the Fr.10 and Fr.11 was both estimated to be 1
      x 10(4) (RF, viral titer reduction factors), indicating that their anti-RSV
      activity was high enough to justify for further analysis. Our preliminary
      analysis showed that the antiviral ingredients were likely to contain phenolic
      compounds including tannins by chemical tests.

PMID- 15261972
TI  - Effects of repeated administration of Uncaria hooks on the acquisition and
      central neuronal activities in ethanol-treated mice.
AB  - The effects of the repeated administration of Uncaria hooks were examined on the
      impaired memory acquisition and the level of neurotransmitters in the cortex,
      hippocampus and striatum in ethanol-treated mice, in comparison with those with L
      deprenyl and N-methyl-D-glucamine as positive controls. Ethanol-induced amnesia
      was significantly ameliorated by repeated administration of methanol extract and
      alkaloid fraction of Uncaria hooks, similar to in the positive controls.
      Treatment with methanol extract and alkaloid fraction of Uncaria hooks
      significantly reduced the ethanol-induced increase of dopamine in the
      hippocampus. The 5-hydroxytryptamine and glutamic acid neuronal activities were
      significantly changed by Uncaria hooks, but not by L-deprenyl, in all examined
      brain tissues of ethanol-treated mice. On the other hand, the GABAergic and
      cholinergic neuronal activities did not show any significant changes by Uncaria
      hooks in any of the examined brain tissues of the ethanol-treated animals. The
      results suggest that the extracts of Uncaria hooks exert a beneficial effect on
      ethanol-induced memory impairment, and that the central 5-hydroxytryptaminergic
      and glutaminergic neuronal systems play an important role in the memory
      acquisition of Uncaria hooks.

PMID- 15261973
TI  - Central nervous system effects of the crude extract of Erythrina velutina on
      rodents.
AB  - The aqueous extract (AE) of Erythrina velutina prolonged the sleep duration
      induced by sodium pentobarbital (control: 6.4 +/- 1.2 min; extract 10 mg/kg, 47.1
      +/- 3.9 min; extract 100 mg/kg, 109.4 +/- 7.2 min; F = 243, P < 0.001). In the
      open field, the extract at the doses of 10 and 50 mg/kg did not changed the
      number of crossings, rearings nor groomings. On the other hand, at the dose of
      200 mg/kg it reduced the number of crossings (q = 6.25, P < 0.05) and groomings
      (q = 3.91, P < 0.05). When exposed during three consecutive days to the open
      field, the control animals showed habituation for crossings (F = 17.56, P <
      0.001) and rearings (F = 14.01, P < 0.001). The same was not true for animals
      treated with 10 mg/kg of the extract (crossings: F = 3.59, P > 0.05; rearings: F
      = 3.62, P > 0.05). At the same dose, the extract blocked the acquisition of foot
      shock memory (P = 0.9219) when compared to the control values (P = 0.0078). Our
      data showed that the crude extract of Erythrina velutina at lower doses
      interferes with mnemonic process for different tasks, while at higher doses, the
      sedative and neuromuscular blocking actions are the main effects.

PMID- 15261974
TI  - Antioxidant activity of DHC-1--a herbal formulation.
AB  - DHC-1, a multiherbal formulation, was tested for its antioxidant activity in
      rats. DHC-1 was investigated at dose levels of 100 mg/kg, p.o. and 200 mg/kg,
      p.o., once daily, for 30 days in normal rats. The levels of superoxide dismutase
      (SOD), catalase (CAT), reduced glutathione (GSH), lipid peroxidation, membrane
      bound enzymes like Ca2+ ATPase, Mg2+ ATPase, Na+K+ ATPase, lipids like
      phospholipid, cholesterol, triglyceride and total proteins were estimated in
      liver, kidneys and heart. Liver glucose-6-phosphate-dehydrogenase (G-6-P-D) was
      also determined. The serum levels of GOT, GPT, alkaline phosphatase, lactate
      dehydrogenase and bilirubin were also estimated. The decrease in the serum
      enzymes may be due to the membrane stabilising action of DHC-1. The inhibition of
      lipid peroxidation and enhancement of antioxidant enzymes (SOD and CAT) along
      with reduced GSH by DHC-1 may be attributed to the antioxidant potential of
      various ingredients present in the formulation. Thus, it can be concluded that
      DHC-1 exhibits an antioxidant activity and could prove beneficial in the
      treatment of various disorders associated with the involvement of reactive oxygen
      species.

PMID- 15261975
TI  - Caraway and caper: potential anti-hyperglycaemic plants in diabetic rats.
AB  - The hypoglycaemic effect of aqueous extracts of Carum carvi (CC) and Capparis
      spinosa L. (CS) fruit were investigated in normal and streptozotocin (STZ)
      diabetic rats. After a single dose or 14 daily doses, oral administration of the
      aqueous CC and CS extracts (20 mg/kg) produced a significant decrease on blood
      glucose levels in STZ diabetic rats (P < 0.001); the blood glucose levels were
      nearly normalised 2 weeks after daily repeated oral administration of both
      aqueous CC and CS extracts (20 mg/kg) (P < 0.001). No highly significant changes
      on blood glucose levels were noticed in normal rats after both acute and chronic
      treatments with CS and CC. In addition, no changes were observed in basal plasma
      insulin concentrations after treatment with these plants in either normal or STZ
      diabetic rats indicating that the underlying mechanism of this pharmacological
      activity seems to be independent of insulin secretion. We conclude that aqueous
      extracts of CC and CS exhibit a potent anti-hyperglycaemic activity in STZ rats
      without affecting basal plasma insulin concentrations.

PMID- 15261976
TI  - Phlorizin-like effect of Fraxinus excelsior in normal and diabetic rats.
AB  - The purpose of this study was to determine the underlying mechanism of the
      hypoglycaemic activity of the aqueous extract perfusion of Fraxinus excelsior L.
      (FE) in normal and streptozotocin-induced diabetic rats. The aqueous extract was
      administered intravenously and the blood glucose changes were determined within
      four hours after starting the treatment. Plasma insulin concentrations and
      glycosuria were determined. The aqueous extract at a dose of 10 mg/kg/h produced
      a significant decrease in blood glucose levels in normal rats (P < 0.001) and
      even more in diabetic rats (P < 0.001). This hypoglycaemic effect might be due to
      an extra-pancreatic action of the aqueous extract of FE, since the basal plasma
      insulin concentrations were unchanged after FE treatment. A potent increase of
      glycosuria was observed both in normal and diabetic rats (P < 0.001). We conclude
      that aqueous extract perfusion of FE caused a potent inhibition of renal glucose
      reabsorption. This renal effect might be at least one mechanism explaining the
      observed hypoglycaemic activity of this plant in normal and diabetic rats.

PMID- 15261977
TI  - Effect of garlic (Allium sativum) on lipid peroxidation in experimental
      myocardial infarction in rats.
AB  - The present study was conducted to elucidate the antioxidant role of garlic oil
      in isoproterenol (IPL)-induced myocardial infarction in rats. In myocardial
      necrosis induced by isoproterenol, a significant increase in serum iron content
      with a significant decrease in plasma iron binding capacity, ceruloplasmin
      activity and glutathione (GSH) level were observed. There was also a significant
      increase in lipid peroxides levels on isoproterenol administration. Activities of
      antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GRD)
      were decreased significantly in heart with isoproterenol-induced myocardial
      necrosis. Garlic oil produced a marked reversal of these metabolic changes
      related to myocardial infarction induced by isoproterenol. In conclusion, garlic
      oil exerts its effects by modulating lipid peroxidation and enhancing antioxidant
      and detoxifying enzyme systems.

PMID- 15261978
TI  - Screening of indigenous plants from South Africa for affinity to the serotonin
      reuptake transport protein.
AB  - Seventy five extracts from 34 indigenous plant species used in South African
      traditional medicine or taxonomically related to these were investigated for
      their affinity to the serotonin reuptake transport protein, making use of an in
      vitro serotonin reuptake transport protein binding assay. Aqueous and 70%
      ethanolic extracts of various plant parts were screened and 45 extracts derived
      from 15 plant species showed affinity. The affinity of 12 extracts from four
      plants was characterized as high (more than 50% inhibition at 5, 1, and 0.5
      mg/ml). Plant species with high affinity to the serotonin reuptake transport
      protein included Agapanthus campanulatus, Boophane disticha, Datura ferox and
      Xysmalobium undulatum. Agapanthus campanulatus yielded high activity in aqueous
      extracts from leaves and flowers. Boophane disticha showed high activity both in
      aqueous and ethanolic extracts of leaves and bulbs. Datura ferox showed high
      activity in aqueous extracts from the seeds and Xysmalobium undulatum showed high
      activity in the ethanolic extract of the whole plant.

PMID- 15261979
TI  - Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax
      pictus, Pueraria thunbergiana and Rhus verniciflua.
AB  - The combined extracts obtained from three Chinese herb medicine, Kalopanax
      pictus, Pueraria thunbergiana and Rhus verniciflua, have been used as
      therapeutics for diabetes mellitus in Korea. In the present study, we have
      investigated their possible anti-inflammatory effects by comparing the potency of
      individual extracts with that of the combined extracts. An individual water
      extract prepared from Kalopanax pictus, Pueraria thunbergiana, and Rhus
      verniciflua was named K-1, P-1, and R-1, respectively. Simultaneously, we also
      prepared the combined extracts from above three plant materials by identical
      methods and named KPR-1. These four extracts were further fractionated into the
      EtOAc extracts, and these were designated as K-2, P-2, R-2, and KPR-2,
      respectively. These eight samples were subjected to the nitrite assays in LPS
      induced macrophage 264.7 cells. KPR-2 exhibited the most pronounced effect on the
      inhibition of NO production among all the extracts. KPR-2 also significantly
      decreased PGE2, and TNF-alpha release. In addition, KPR-2 showed in vivo anti
      inflammatory activity against acute paw edema induced by carrageenan in rats.
      When analgesic activity was measured by the acetic acid-induced abdominal
      constriction and hot plate test, KPR-2 showed a dose-dependent inhibition in
      animal models. These results suggested that the mixture extract and successive
      fractionation could lead to the better use of anti-inflammatory medicinal crude
      drugs.

PMID- 15261980
TI  - Investigation of Lepechinia graveolens for its antioxidant activity and phenolic
      composition.
AB  - A bioguided separation of Lepechinia graveolens (Reg.) Epling. (Lamiaceae) for
      antioxidant activity was carried out. The ethyl acetate fraction (EAF) from the
      methanolic extract was chromatographed on Sephadex LH-20 affording five active
      fractions. The radical scavenging activity of each fraction, as well as that of
      the isolated compounds, was tested using three different methods. The major
      isolated antioxidant compounds were identified as luteolin-7-O-glucuronide,
      rosmarinic acid, and rosmarinic acid methyl ester by means of 1H and 13C NMR and
      mass spectrometry. Twenty other minor phenolic compounds were determined by
      liquid chromatography-negative electrospray ionization tandem mass spectrometry.
      They included hydroxycinnamic acid derivatives, flavonoids and phenolic
      diterpenes. The major phenolic compound was found to be rosmarinic acid, which
      was quantitatively determined by high-performance liquid chromatography (HPLC)
      diode array detector (DAD). The content of rosmarinic acid was 2.8% (referred to
      dry weight), this amount being around 30% of the total phenolic content (TPH) of
      the crude extract. It can be concluded that the antioxidant activity of
      Lepechinia graveolens was mainly due to rosmarinic acid, which allows this plant
      species to be considered as a potential new source of this well known natural
      antioxidant.

PMID- 15261981
TI  - Vasorelaxant effect of new neo-clerodane diterpenoids isolated from Croton
      schiedeanus.
AB  - The vasorelaxant effect of two new neo-clerodane diterpenoids, (12R)-12
      hydroxycascarillone and 5beta-hydroxy-cis-dehydrocrotonin, in addition to the
      known cis-dehydrocrotonin and trans-dehydrocrotonin, all them previously isolated
      by us from Croton schiedeanus Schlecht, was studied in isolated aorta rings
      contracted by high K+ (80 mM) or phenylephrine (1 microM). According to their
      IC50 values to KCl induced contraction, the potency order was (12R)-12
      hydroxycascarillone > cis-dehydrocrotonin > 5beta-hydroxy-cis-dehydrocrotonin >
      trans-dehydrocrotonin (0.3, 1.5, 96 and >100 mM, respectively). The possible
      cooperativity between diterpenoid compounds and the predominant flavonoid
      (ayanin) was studied. The vasorelaxant activity of cis-dehydrocrotonin and ayanin
      was increased when both compounds were incorporated simultaneously to the aortic
      rings precontracted with phenylephrine. These results suggest that Croton
      schiedeanus induces its effects via the synergistic actions of several
      vasodilator substances, among which neo-clerodane diterpenoids play an important
      role.

PMID- 15261982
TI  - Acute and chronic antiinflammatory effects of Hedera colchica in rats.
AB  - Hedera helix and Hedera colchica are the members of Araliaceae family. In the
      present study, we tested the possible antiinflammatory effects of crude (CSE) and
      purified (SPE) extracts of Hedera colchica in carrageenan- and cotton pellet
      induced acute and chronic inflammation models in rats. Both CSE and SPE of Hedera
      colchica were found to have antiinflammatory effects. The most potent drug was
      found as indomethacin (90%) in the 4 h measurements, while SPE (83%) and CSE
      (55%) of Hedera colchica in 100 mg/kg doses were found to have quite potent
      effects in acute phase of inflammation, in respect to control values. For testing
      chronic antiinflammatory (antiproliferative) effects, cotton pellet granuloma
      test was conducted. SPE was found as the most potent drug in chronic phase of
      inflammation with an effect of 64.32%. Indomethacin was found more potent than
      the CSE of Hedera colchica, and potency was found as 61.2 and 58%, respectively.

PMID- 15261983
TI  - Effect of Symplocos racemosa Roxb. on gonadotropin release in immature female
      rats and ovarian histology.
AB  - In the present study we are reporting in vivo effect of aqueous extracts of
      Symplocos racemosa Roxb. (Fam. Symplocaceae) on serum FSH and LH levels in
      immature female Sprague-Dawley rats under basal conditions. Symplocos racemosa is
      used in Indian System of Medicine (ISM) for various female disorders. Aqueous
      extract on oral administration significantly stimulated serum FSH level (P <
      0.016) along with the rise in serum LH level (P < 0.001). Moreover,
      histopathological studies revealed enhanced folliculogenesis, presence of mature
      follicles and detached oocytes, which are result of increased FSH and LH levels.
      Further, an increase in the ovary weight of treated animals was found due to
      observed FSH surge. These results are in concordance with the traditional use of
      the drug for female disorders.

PMID- 15261984
TI  - The traditional categories of fluoroacetate poisoning signs and symptoms belie
      substantial underlying similarities.
AB  - Sodium monofluoroacetate (Compound 1080) has been widely used around the world as
      a vertebrate pest control agent. Following ingestion of 1080 there is a latent
      period, during which the compound is metabolised into a toxic form, before the
      onset of symptoms. The timing of this period varies significantly between species
      as does the median lethal dose. Traditionally different species have also been
      classified into groups depending on the primary organ system involved in 1080
      toxicosis (cardiac, nervous, or mixed signs/symptoms). However, general
      acceptance of this method of classification has obscured the fact that several
      signs of fluoroacetate poisoning are common to most vertebrate species. This
      paper reviews five decades of literature on the signs/symptoms of fluoroacetate
      poisoning in vertebrates and concludes that there is little justification for the
      division of animals poisoned by fluoroacetate into symptomatic groups.

PMID- 15261985
TI  - New data on biological effects of chlorhexidine: Fe2+ induced lipid peroxidation
      and mitochondrial permeability transition.
AB  - Chlorhexidine (CHX) is a bis-bis-guanide with anphipatic and antiseptic
      properties and is largely used in dentistry, mainly for management of periodontal
      problems and in oral pre-operatory procedures. The present study concerns the
      effect of CHX on lipid peroxidation, mitochondrial permeability transition (MPT),
      and the interaction of CHX with ferritin (HoSF). CHX (100 microM) increased iron
      release from HoSF by approximately 13-fold when compared to control values. CHX
      also increased iron-dependent lipid peroxidation. MPT induced by CHX was
      protected by ethylene glycol-bis(beta-aminoethyl-ether)-N,N,N',N'-tetraacetic
      acid (EGTA), dithiothreitol (DTT), and cyclosporin A (CsA), showing a Ca2+
      dependent effect, in which oxidation of thiol groups is involved, as well as the
      involvement of the transmembrane proteinaceous pore. BHT, catalase or o
      phenanthroline did not protect MPT induced by CHX. This suggests that a ROS
      independent mechanism is involved in the induction of MPT.

PMID- 15261986
TI  - Comparative effects of technical toxaphene, 2,5-dichloro-3-biphenylol and
      octabromodiphenylether on cell viability, [Ca2+]i levels and membrane fluidity in
      mouse thymocytes.
AB  - Flow cytometric studies of mouse thymocytes show that technical toxaphene (10-20
      ppm) and 2,5-dichloro-3-biphenylol (PCB 9-OH) (5-10 ppm) kill cells and cause an
      increase in intracellular calcium concentration, [Ca2+]i, whereas commercial
      octabromodiphenylether (OBDE) has no effect. The cell death is not a result of
      the rise of [Ca2+]i, since the divalent cation ionophore, ionomycin, causes a
      large elevation in [Ca2+]i without cell death. We have studied effects of these
      compounds on membrane fluorescence polarization, a measure of membrane fluidity,
      using 1,6-diphenyl-1,3,5-hexatriene (DPH). We find that toxaphene causes a
      decrease in membrane fluidity in the concentration range associated with cell
      death, whereas PCB 9-OH causes an increase in fluidity and OBDE has no effect.
      These observations suggest that alterations of membrane fluidity of thymocytes,
      whether it be an increase or decrease, can cause cytotoxicity.

PMID- 15261987
TI  - The effects of tobacco smoke on plasma alpha- and gamma-tocopherol levels in
      passive and active cigarette smokers.
AB  - Tobacco smoke is one of the causes of oxidative stress that is leading to
      attenuation of the antioxidative body protective barrier by means of decreasing
      the levels of intra- and extracellular antioxidants. The effect of tobacco smoke
      on plasma levels of two main forms of Vitamin E, alpha- and gamma-tocopherol, in
      passive smokers (urinary cotinine concentration 50-500 microg/L) and active
      smokers (urinary cotinine concentration >500 microg/L) were studied. Slight, but
      statistically significant decreases in plasma alpha-tocopherol level in passive
      and active smokers in comparison with non-smokers (by 5.7% and 9.2%,
      respectively) were found. The plasma gamma-tocopherol levels remained unchanged.
      The Pearson's correlation coefficient for the plasma alpha-tocopherol level and
      the urinary cotinine concentration in passive and active smokers was -0.431, P =
      0.004 and -0.534, P < 0.001, respectively, and for gamma-tocopherol in similar
      conditions -0.190, P = 0.217 and 0.346, P = 0.027, respectively. The obtained
      results indicate the secondary role that alpha- and gamma-tocopherol play in the
      process of tobacco smoke free radical scavenge, or they may also reflect the body
      increased anti-oxidative mobilization in response to oxidative stress evoked by
      tobacco smoke.

PMID- 15261988
TI  - Potent inhibition of gap junctional intercellular communication by 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in BALB/c 3T3 cells.
AB  - The chlorohydroxyfuranones (CHFs) MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone], MCA [3,4-dichloro-5-hydroxy-2(5H)-furanone], CMCF [3-chloro-4
      (chloromethyl)-5-hydroxy-2(5H)-furanone], and MCF [3-chloro-4-methyl-5-hydroxy
      2(5H)-furanone] are genotoxic disinfection by-products of drinking water
      chlorination. MX, MCA, and MCF also promote foci formation in the two-stage cell
      transformation assay. The cellular mechanisms underlying this apparent
      promotional effect are not known. In the present study, the effects of MX, MCA,
      CMCF, and MCF on gap junctional intercellular communication (GJIC) were measured
      in BALB/c 3T3 cells using the scrape loading dye technique. The effect of MX on
      apoptosis in the same cell line was explored by assaying caspase-3-like protease
      activity. All the four CHFs inhibited GJIC after 30 min exposure in a dose
      dependent fashion but there was a marked difference in the ranges of their active
      concentrations. MX was almost as potent an inhibitor of GJIC (inhibition at
      nanomolar concentrations) as 12-O-tetradecanoylphorbol-13-acetate (TPA) (positive
      control), while MCA was 10 times weaker, CMCF 10,000 times weaker, and MCF 20,000
      times weaker than MX. After prolonged exposure periods (up to 6 h), GJIC
      recovered somewhat upon MX and MCA exposures, the inhibition of GJIC by MCF
      remained constant but CMCF showed an irreversible increasing inhibitory effect.
      MX caused apoptosis as a "window" effect at concentrations 2000-4000-fold higher
      than those needed to inhibit GJIC. The results indicate that MX is a potent
      inhibitor of GJIC in BALB/c 3T3 cells and this inhibition might be one mechanism
      by which MX can promote malignant foci formation. MCA also has a specific
      potential to inhibit GJIC whereas MCF and CMCF affected GJIC at concentrations,
      similar to those evoking genotoxicity in vitro.

PMID- 15261989
TI  - Reduction of erythrocyte catalase and superoxide dismutase activities in male
      inhabitants of a cadmium-polluted area in Jinzu river basin, Japan.
AB  - Cadmium (Cd) is a toxic heavy metal which causes oxidative damage in organisms.
      In this study, we investigated the activities of the antioxidant enzymes
      erythrocyte catalase and copper/zinc superoxide dismutase (Cu/Zn-SOD) in 22 male
      inhabitants of the Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd
      group). The reference group consisted of 21 male inhabitants from an area that
      was not polluted with Cd (reference group). Urinary Cd levels and two renal
      tubular dysfunction markers in urine, alpha1-microglobulin (alpha1-m) level and N
      acetyl-beta-D-glucosaminidase (NAG) activity, were significantly elevated in the
      Cd group. Catalase and Cu/Zn-SOD activities were significantly reduced in the Cd
      group as compared to the reference group. Significant negative correlation was
      observed between the activities of these two antioxidant enzymes and urinary Cd
      levels. We also observed significant negative correlations between activities of
      these two antioxidant enzymes and the renal tubular dysfunction markers. Our
      results indicate that erythrocyte catalase and Cu/Zn-SOD activities are reduced
      as a result of long-term Cd exposure. This may be linked to renal tubular
      dysfunction in the inhabitants of the Cd-polluted area.

PMID- 15261990
TI  - Acute exposure to cobalt induces transient methemoglobinuria in rats.
AB  - We observed transient excretion of dark-brown urine after acute exposure to
      cobalt in rats and investigated the mechanism of it. We injected cobalt into rats
      s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ
      samples at the indicated times after injection. Biochemical and histopathological
      examinations of these samples were conducted. Obvious macroscopic and biochemical
      methemoglobinuria was observed just after injection of cobalt, but the level of
      urinary methemoglobin decreased gradually, almost disappearing by 24 h. The
      levels of cobalt in peripheral blood and urine showed a very similar pattern to
      that of methemoglobinuria. Neither anemia nor bilirubinemia was observed,
      indicating no extrarenal intravascular hemolysis. Pathological examination of the
      kidneys revealed that the glomerular capillaries were filled with red blood cells
      at 1 h after injection. Electron microscopy showed deformed red blood cells in
      the glomerular capillaries and condensed hemoglobin in Bowman's capsule that
      passed through the basement membrane. There were no trends toward increases in
      plasma levels of creatinine or blood urea nitrogen. These results indicate that
      exposure to cobalt induces transient methemoglobinuria through the lysis of red
      blood cells and oxidation of iron in hemoglobin at the glomerular capillaries
      without causing renal dysfunction.

PMID- 15261991
TI  - Effect of in vitro estrogenic pesticides on human oestrogen receptor alpha and
      beta mRNA levels.
AB  - Nine widely distributed pesticides were recently demonstrated to possess
      potential estrogenic properties in oestrogen receptor (ER) transactivation and/or
      E-screen assays. We tested the effect of these nine pesticides on the human
      ERalpha and ERbeta mRNA steady state levels in the mamma cancer fibroblast MCF
      7BUS cells using on-line RT-PCR. Like 17beta-oestradiol (E2), fenarimol
      significantly decreased the ERalpha and increased the ERbeta mRNA level.
      Endosulfan and pirimicarb alone decreased the ERalpha mRNA level weakly. After co
      exposure with E2, all the tested pesticides counteracted the E2-induced decrease
      of the ERalpha mRNA level, but only significantly for prochloraz, dieldrin, and
      tolchlofos-methyl. Alone no pesticides affected the ERbeta mRNA level
      significantly, but chlorpyrifos increased the mRNA level weakly. Co-exposure with
      E2 elicited a significant increased ERbeta mRNA level by prochloraz, fenarimol,
      endosulfan, dieldrin, and tolchlofos-methyl, whereas no significant effect of the
      carbamate pesticides on the ERbeta mRNA level was observed. This study
      demonstrated that organochlor and organophosphorous pesticides possess the
      ability to interfere with the ERalpha and ERbeta mRNA steady state levels.

PMID- 15261992
TI  - Genotoxic potentiality of aqueous extract prepared from Chrysobalanus icaco L.
      leaves.
AB  - Plants have been related to our lives, being used as medicine, regardless of
      scientific evidence of side effects. This work analyses the toxicological effects
      of Chrysobalanus icaco L. aqueous extract, used in different pathologies. It was
      studied through: (i) alteration of plasmid pUC 9.1 topology; (ii) survival of
      bacterial strains submitted, or not, to previous treatment with SnCl2; (iii)
      transformation efficiency of E. coli strain by the treatment with the plasmid pUC
      9.1. In (i), the treatment of the plasmid resulted in DNA single-strand breaks
      (SSB). A decrease of the lethal effect induced by SnCl2 in presence of the
      extract was found, while no C. icaco bacterial survival reduction was observed.
      The transformation efficiency of the plasmid was also reduced. Results suggest
      that the extract could present a potential genotoxic effect, as demonstrated
      either by the induction of SSB in plasmid or in transformation efficiency
      experiments. Finally, it presents an antioxidant action.

PMID- 15261993
TI  - Response to: artemisinin derivatives: toxic for laboratory animals, safe for
      humans?

PMID- 15261995
TI  - Paratuberculosis in farmed and free-living wild ruminants in the Czech Republic
      (1999-2001).
AB  - Due to the occurrence of the infection of Mycobacterium avium subspecies
      paratuberculosis among domestic ruminants and the rapid development of farmed
      deer industry and the market of cloven-hoofed game we have carried surveys of
      paratuberculosis, beginning in 1997, in the most common four species of wild
      ruminants in the Czech Republic [Pavlik et al., Vet. Microbiol. 77 (2000) 231
      251]. From 1999 the prevalence of paratuberculosis has been slightly reduced in
      all three types of husbandry of wild ruminants. Nevertheless paratuberculosis has
      been diagnosed in wild ruminants in three districts, in four game parks and in
      five farms. M. a. paratuberculosis was isolated from 128 (5.3%) out of 2,403 wild
      ruminants of four animal species: 106 red deer, 2 roe deer, 4 fallow deer and 16
      mouflons. In red deer farms, the highest number of clinical paratuberculosis
      cases was in yearling deer. RFLP type B-C1 of M. a. paratuberculosis predominated
      during the second period (1999-2001) in all types of husbandry with no
      relationship to wild ruminant species. New "cattle" RFLP types B-C5 and B-C16 of
      M. a. paratuberculosis were described in infected farmed red deer and one
      "intermediate" RFLP type R-I4 in fallow deer from one game park. The survival of
      M. a. paratuberculosis was found to be 4 months during winter in the pasture
      after destocking of all cattle infected with paratuberculosis. We found that non
      vertebrates, wild ruminants or non-ruminant wildlife can be vectors and
      potentially become a risk factor in the spread of M. a. paratuberculosis
      infection.

PMID- 15261996
TI  - Fecal shedding of Helicobacter spp. by co-housed Australian sea lions (Neophoca
      cinerea) and Australian fur seals (Arctocephalus pusillus doriferus).
AB  - With the emergence of Helicobacter species as agents of gastrointestinal disease
      within a broad range of animal hosts, there is growing awareness of the need to
      identify such species and the potential role(s) they play within the intestine.
      Of interest in this study are captive seals and sea lions, where close proximity
      to one another may enhance the transmission of pathogens, in particular
      Helicobacter. The feces of several captive Australian sea lions and Australian
      fur seals were assessed for the occurrence of Helicobacter over 31 days. The
      presence of Helicobacter, detected by the polymerase chain reaction (PCR) varied
      over time and at times could not be detected. Helicobacter species were detected
      in five of the six animals examined of which two species were identified. This is
      the first report of Helicobacter species in captive seals and demonstrates the
      diversity and potential role(s) they may play in the gut of these animals.

PMID- 15261997
TI  - Antimicrobial resistance and resistance genes in Staphylococcus aureus strains
      from rabbits.
AB  - Fifty-six Staphylococcus aureus isolates recovered between 1998 and 2003 from 31
      rabbit farms with and without problems of chronic staphylococcosis, were screened
      for resistance to enrofloxacin, erythromycin, gentamicin, lincomycin, neomycin,
      penicillin and tetracyclines using the agar dilution test. For penicillin, a disk
      diffusion test was also performed. The detection of tetP(B), tet(K), tet(L),
      tet(M), tet(O), tet(T), tet(W), erm(A), erm(B), erm(C) and mec(A) genes was done
      via a PCR assay. Four isolates showed resistance to erythromycin and lincomycin.
      These isolates were positive for the erm(C) gene in the PCR. Eleven strains were
      resistant to tetracyclines and all harboured the tet(K) gene. In the agar
      dilution test, five isolates showed resistance to penicillin, whereas in the disk
      diffusion test 12 isolates showed resistance. None of these 12 resistant isolates
      carried the mec(A) gene. Only one strain showed resistance to gentamicin, and all
      strains were susceptible to enrofloxacin and neomycin. This study demonstrates
      that resistance to antimicrobial agents in S. aureus isolates originating from
      rabbits is relatively rare compared to resistance in S. aureus isolates
      originating from other animals and humans.

PMID- 15261998
TI  - Mouse mastitis model of infection for antimicrobial compound efficacy studies
      against intracellular and extracellular forms of Staphylococcus aureus.
AB  - Despite the general in vitro susceptibility of Staphylococcus aureus isolates
      that cause infectious bovine mastitis, the pathogen remains difficult to
      eradicate with the available antibiotics. The capacity to survive intracellularly
      has been proposed as a factor contributing to the persistence of S. aureus in the
      bovine mammary gland. The costs associated with the use of cows or goats to
      assess the in vivo efficacy of new antibacterial compounds constitute a major
      drawback. Therefore, in the present study, a mouse model of intramammary
      infection has been characterized for in vivo testing of new experimental drugs.
      An inoculum of 100 CFU of S. aureus per gland caused an important level of
      infection with minimal tissue damage as observed at 24 h post-inoculation. By
      microscopy, polymorphonuclear neutrophil cell infiltration of the infected
      mammary glands was observed to increase over time. At 12-24 h of infection, the
      pathogen was primarily found alive and dividing in neutrophils and occasionally
      within mammary epithelial cells. Intramuscular or intravenous injections of
      cephapirin at t = 0 and 10 h reduced the number of CFU/g of gland in a dose
      dependent manner. In conclusion, the mouse model of infectious mastitis proposed
      here is suitable for primary evaluation of experimental drugs after parenteral
      treatment of intramammary infection with a pathogen such as S. aureus that
      presents both intracellular and extracellular phases of growth.

PMID- 15261999
TI  - Evaluation of the German cockroach (Blattella germanica) as a vector for
      verotoxigenic Escherichia coli F18 in confined swine production.
AB  - German cockroaches are common pests of confined swine production in North
      Carolina and other southeastern states. Vector competence of German cockroaches
      for one of the most important porcine bacterial pathogens, verotoxigenic
      Escherichia coli F18, was evaluated in laboratory bioassays using a culturing
      approach followed by multiplex PCR. In addition, the populations of fecal
      coliforms from the feces of piglets and cockroaches collected from a swine
      nursery were assessed. Viable and virulent cells of E. coli F18 were detected in
      cockroach feces for up to 8 days after the initial exposure. The population of
      fecal coliforms in cockroach feces was high (4.4 x 10(5) CFU g(-1)) and
      comparable to that of piglet feces (1.9 x 10(6) CFU g(-1)). This study
      demonstrates that cockroaches may serve as important mechanical vectors of
      pathogenic E. coli. Integrated management of cockroach populations should be
      incorporated into the disease prevention and control programs in the swine
      industry.

PMID- 15262000
TI  - Attaching and effacing Escherichia coli isolated from dogs in Brazil:
      characteristics and serotypic relationship to human enteropathogenic E. coli
      (EPEC).
AB  - Escherichia coli isolates recovered from 182 fecal specimens from dogs up to five
      months old from the cities of Sao Paulo and Campinas, SP, Brazil, were examined
      by polymerase chain reaction (PCR) for several virulence factors and properties.
      The eae gene was found in 23 isolates of E. coli from 22 dogs, 19 of 146 (13%)
      from dogs with diarrhea and 3 of 36 (8.3%) from dogs with no diarrhea. Two
      different eae+ isolates were recovered from one dog with diarrhea. Isolates from
      two dogs with diarrhea harbored the bfpA gene, and none of the isolates possessed
      genes for enterotoxins, the EAF plasmid or Shiga toxins. PCR showed that, among
      the 23 isolates, eight were positive for beta intimin, six for gamma, two for,
      one for alpha, one for kappa, and five showed no amplification with any of the
      nine pairs of specific intimin primers used. PCR also showed that the LEE (locus
      of enterocyte effacement) was inserted in selC in four isolates, likely in pheU
      in seven isolates, and in undetermined sites in twelve isolates. Fifteen isolates
      adhered to HEp-2 cells and were fluorescence actin staining (FAS) positive. The
      predominant adherence pattern was the localized adherence-like (LAL) pattern. The
      eae-positive isolates belonged to a wide diversity of serotypes, including
      O111:H25, O119:H2 and O142:H6, which are serotypes that are common among human
      EPEC. These results confirmed the presence of EPEC in dogs (DEPEC) with and
      without diarrhea. The virulence factors found in these strains were similar to
      those in human EPEC, leading to the possibility that EPEC may move back and forth
      among human and canine populations.

PMID- 15262001
TI  - Characterization of the pCS20 region of different Ehrlichia ruminantium isolates.
AB  - Heartwater is a serious tick-borne disease of ruminants caused by the rickettsial
      organism Ehrlichia (Cowdria) ruminantium. A diagnostic test, targeting the pCS20
      genomic region and using PCR amplification and probe hybridization, detects E.
      ruminantium infection in ticks and animals. However, only the pCS20 sequence of
      the Crystal Springs E. ruminantium isolate is available and the existence of
      sequence variation amongst different E. ruminantium isolates has not been
      determined. Primers were designed from the published pCS20 sequence to obtain
      sequences of the pCS20 region of various E. ruminantium isolates. These primers
      were unable to amplify the pCS20 region from genomic Welgevonden DNA and genome
      walking was used to characterize the pCS20 region. This technique showed that the
      published pCS20 sequence is from a chimeric clone. Sequences of the pCS20 region
      of 14 different E. ruminantium isolates were determined after amplification with
      newly designed primers. Sequencing data indicated that West African E.
      ruminantium isolates are highly conserved, whereas more variation occurs amongst
      the southern African isolates. These results facilitated the design of a short
      pCS20 probe and a large PCR target that improved the sensitivity of the E.
      ruminantium detection assay.

PMID- 15262002
TI  - Assessment of an optimized dog-culling program in the dynamics of canine
      Leishmania transmission.
AB  - In Brazil, zoonotic visceral leishmaniasis (ZVL) control programs based on the
      mass elimination of seropositive dogs have failed to reduce the number of
      leishmaniasis cases. However, these programs have been done under sub-optimal
      conditions. We studied a cohort of dogs in an urban area in Brazil to determine,
      whether a dog-culling program optimized with: (i) replacement of a relatively low
      sensitivity indirect immune-fluorescent test on blood eluate by a more sensitive
      enzyme-linked immunosorbent assay on serum blood samples; (ii) shortening of the
      time interval from serodiagnosis to removal of dogs; (iii) screening a high
      proportion of the dog population could reduce the incidence of canine Leishmania
      infection (CLI). The study ran from December 1997 to July 2000, with four follow
      up assessments performed at approximately 8-month intervals. All dogs
      seropositive for anti-Leishmania antibodies were promptly eliminated. A large
      number of new dogs immigrated to the study area throughout the study period. They
      comprised 43.8-49.8% of the cohort at each follow-up assessment, and upto 15% of
      them already had Leishmania infection. Overall, 42 news cases of CLI were
      identified, for a crude incidence rate of 11.8 cases per 100 dog-years (95% CI
      8.6-15.6). In the first, second, third and fourth follow-up assessments the
      incidence rates were 8.2 (95% CI 3.0-17.9), 12.2 (95% CI 6.3-21.2), 16.4 (95% CI
      8.5-28.6) and 13.6 (95% CI 7.1-23.8), respectively. There was no statistically
      significant change in these rates throughout the study period. Our results
      suggest that dog-culling programs do not reduce the incidence of CLI, even with
      an optimized intervention. Possible reasons for this failure include: currently
      available serologic methods lack sufficient sensitivity and/or specificity to
      accurately identify all infected dogs warranting removal in order to prevent
      Leishmania transmission; destroyed dogs are immediately replaced by susceptible
      puppies, and quite often, by already infected dogs; and other reservoirs may be
      involved in maintaining canine infection. Further efforts on ZVL control should
      be directed to developing new strategies or to testing control methods already in
      place with properly designed trials.

PMID- 15262003
TI  - Seroprevalence of Toxoplasma gondii and Neospora caninum in captive maned wolves
      (Chrysocyon brachyurus) from southeastern and midwestern regions of Brazil.
AB  - The main purpose of the present study was to investigate the occurrence of
      antibodies against T. gondii and N. caninum in captive maned wolves from Brazil,
      considering that little information is available at the literature about
      infections by these parasites in this wild animal. Serum samples were obtained
      from 59 maned wolves originated from six zoos and from one ecological reserve of
      the southeastern and midwestern regions of Brazil. To detect IgG antibodies
      against T. gondii, an ELISA protocol was used and the results were expressed as
      ELISA reactivity indexes (EI). Serology for N. caninum was carried out by
      indirect fluorescent antibody test (IFAT) and cut-off titers were established at
      1:25 dilution. From the total of the analyzed samples, 44 (74.6%) were
      seropositive for T. gondii and only 5 (8.5%) for N. caninum. Seropositivity for
      T. gondii ranged from 0 to 100% in the seven different origin locals, with rates
      over 50% among the six zoos, whereas no positivity was found in the samples from
      ecological reserve. For N. caninum, seroprevalence varied from 0 to 50% in the
      different locals, with the highest rates also detected in zoos. Seroprevalence
      for T. gondii was strongly related with age, with rates significantly higher
      among adult wolves (91.7%) when compared to newborn or young animals.
      Seropositive samples for N. caninum were found predominantly in adult wolves. For
      both parasites, seroprevalence did not show a significant distinction in relation
      to gender. Although seroprevalence for T. gondii was significantly higher when
      compared to N. caninum in the Brazilian captive maned wolves tested, these
      findings reflect the great exposure of this species to T. gondii and, in lower
      extension, to N. caninum. Also, the present study demonstrated for the first time
      the presence of antibodies to N. caninum in wild life from South America.

PMID- 15262004
TI  - Immune response and antigen recognition in non-pregnant ewes experimentally
      infected with Neospora caninum tachyzoites.
AB  - The cellular and humoral responses as well as the antigen recognition during the
      acute stage of a Neospora caninum (NC) infection were investigated in non
      pregnant ewes. The experimentally infected ewes developed specific
      lymphoproliferative and humoral responses within 2 weeks post-infection (PI). The
      magnitude of the cellular response showed large variations between animals. A
      significant decrease in the proliferative response to Con A mitogen and N.
      caninum, Toxoplasma gondii (TG) antigens was recorded on day 21 post-infection
      (PI). The humoral response and the pattern of antigen recognition were similar
      among infected ewes. Proteins of 44, 42, 40, 39 and 28 kDa were intensively
      recognized by the infected animals during the experiment. The 42 and 28 kDa
      antigens should be considered as useful for the diagnostic of N. caninum
      infection, as the intensity of recognition infection of the other antigens had
      decreased markedly 8 weeks post-infection. For some antigens a sequential
      recognition was recorded. The 59, 54 and 38-37 kDa proteins were frequently
      recognized by infected sera during the first weeks of the infection, but
      recognition of these antigens was absent or rare at the end of the experiment.
      These antigens could be related to the acute stage of the infection.

PMID- 15262005
TI  - Epidemiological aspects of filariosis in dogs on the coast of Parana state,
      Brazil: with emphasis on Dirofilaria immitis.
AB  - The present study determined the prevalence and geographical distribution of
      Dirofilaria immitis and other filariae, from dogs in littoral areas of Parana
      state, in Brazil. This survey spanned eight months, between 1998 and 1999, and
      was also designed to compare the efficacy of different tests for diagnosis of
      heartworm infection in that area. Blood samples were collected from 256 native
      owned dogs distributed along the Parana coastal area. Five diagnostic procedures
      were used: direct smear examination, the Knott's modified test, filtration assay,
      and two heartworm antigen detection kits. A follow-up imaging exam was performed
      to support the heartworm diagnosis. The imaging diagnosis included radiographic
      and ultrasonographic exams of six dogs that had positive results for the
      heartworm antigen detection kits, but showed different microfilarial burdens. The
      presence and severity of radiographic and ultrasonographic signs were compared
      with the results obtained in microfilariae detection and antigen tests.
      Diagnostic parasitology results indicated that 31.25% of the dogs were
      microfilaremic. Three different microfilariae were recovered: D. immitis,
      Dipetalonema reconditum, and the third (mf3) was not identified. D. reconditum
      was the species with the highest prevalence: 22.6%. In general, D. immitis
      prevalence was 5.47% (28.57% occult infections), but it varied along the coast
      and the range was from 0 to 20%. No correlation could be established between the
      overall scores for microfilarial counts (small or large numbers) and the severity
      of radiographic results or the likelihood of detecting filariae in the pulmonary
      artery using echocardiography. The finding of a different type of microfilaria
      (mf) suggested the existence of a third species in Parana state, whose prevalence
      was 4.68%. These results show that to obtain a reliable diagnosis of heartworm
      infection, antigen detection kits are indicated. Knott's test or filtration
      should be performed to confirm microfilaremia and not for diagnosis of heartworm
      infection. Imaging tests support parasitology exams and add more about severity
      of infection. The northern areas, specially Guaraquecaba and Ilha das Pecas,
      presented the highest number of heartworm-infected dogs.

PMID- 15262006
TI  - Efficacy of a single milbemycin oxime administration in combination with
      praziquantel against experimentally induced heartworm (Dirofilaria immitis)
      infection in cats.
AB  - The efficacy of a combination of milbemycin oxime and praziquantel in preventing
      the establishment of experimentally induced heartworm (Dirofilaria immitis)
      infection was investigated in a study involving 24 young domestic short-hair
      cats. The animals were inoculated with 50 infective larvae on day 0. Subsequently
      they were divided into two groups of 12 animals each. The animals in group 1 were
      treated once with medicated tablets containing 4 mg milbemycin (minimum dose 2
      mg/kg body weight) and 10 mg praziquantel (MILBEMAX) on day 30 after infection.
      Cats in group 2 received placebo tablets on the same day. On day 183 post
      infection a blood sample was taken from each animal before euthanasia and
      necropsy. The blood samples were tested for the presence of microfilariae and the
      necropsied animals were examined for the presence of adult worms. Microfilariae
      were not found in any of the investigated cats. No heartworms were found in the
      animals in group 1 (treated with medicated tablets). Out of the 12 placebo
      treated cats 1 was heartworm-free, whereas all the others were found to be
      infected with 1-3 adult heartworms.

PMID- 15262007
TI  - Effects of short-chain fatty acids and lactic acids on survival of
      Oesophagostomum dentatum in pigs.
AB  - The direct influence of intracaecal infusion of short-chain fatty acids (SCFA)
      and lactic acids (LA) on already established Oesophagostomum dentatum infection
      in cannulated pigs was investigated. We tested the hypothesis that the previously
      discovered anti-parasitic effect of inulin is mediated through its metabolic
      products SCFA and LA by infusing into cannulated pigs these compounds in amounts
      approximating to those produced in the pigs large intestine and caecum during the
      metabolism of inulin. The experiment comprised of 18 pigs--2 groups of 9 pigs in
      each. The normal diet used in the experiment was based on barley flour with
      insoluble fibre from oat husk with added soybean meal, vitamins and minerals.
      After 2 weeks of adaptation to the diet all the pigs were inoculated with 6,000
      infective larvae of O. dentatum. Six weeks later, surgery on all pigs was
      performed to install cannulas into caeci. At 7 weeks post-infection (p.i.) the
      SCFA and LA infusion was initiated in Group 1 (experimental) pigs; at the same
      time pigs in Group 2 (controls) were infused with saline. At week 10 p.i., all
      pigs were killed and their worm burdens determined. SCFA and LA infused pigs
      exhibited markedly reduced fecal egg counts and worm recoveries (98 and 92%
      reduction, respectively, compared to saline controls). The results from this
      study demonstrate that SCFA and LA have a significant negative influence on
      established O. dentatum infection in growing pigs. The results also show that the
      type of dietary carbohydrates fed and its intestinal degradation can yield
      metabolic by products that profoundly influence helminth survival.

PMID- 15262008
TI  - Resistance to benzimidazole and macrocyclic lactone anthelmintics in cattle
      nematodes in Argentina.
AB  - In April 2003, persistent scouring and ill-thrift that was reported in calves
      form an intensive beef rearing operation in central Argentina despite treatments
      with benzimidazole and ivermectin. In order to conduct a controlled faecal egg
      count reduction test on this herd, 40 calves 5-8-months-old were selected on the
      basis that they had a nematode eggs per gram (epg) of faeces count greater than
      150. Animals were divided into four groups (1-4) of 10 calves. Calves of groups 1
      3 were treated, respectively, with subcutaneous injection of ivermectin (200
      mcg/kg), ricobendazole (4 mg/kg) and levamisole (7.5 mg/kg), while calves of
      group 4 remained as untreated controls. The egg count reductions carried out 10
      days later were lower than 15% in calves treated with ivermectin and
      ricobendazole, but 100% in animals receiving levamisole. Pooled post-treatment
      faecal cultures showed larval percentages of 92 and 95 for Haemonchus and 8 and 5
      for Cooperia in the faeces of calves treated with ivermectin and ricobendazole,
      respectively. This is the first reported case of Haemonchus parasiting cattle
      showing simultaneous resistance to avermectins and benzimidazole type
      anthelmintics.

PMID- 15262009
TI  - The use of PCR to detect Neospora caninum DNA in the blood of naturally infected
      cows.
AB  - Twelve 2-year old heifers in their fifth month of gestation when pregnancy tested
      were used in this study. Six heifers aborted at approximately 4 months of
      gestation and had blood samples drawn less than 6 weeks after the abortions were
      identified. Blood samples were also drawn from three sero-positive pregnant and
      three sero-negative pregnant heifers. DNA was isolated from the samples and a 350
      bp fragment of the Nc-5 gene was PCR amplified using primer pair Np21+ and Np6+.
      Also, the Internal Transcribed Spacer 1 (ITS1) was PCR amplified using Tim 3 and
      Tim 11 primer pair. The Nc-5 gene fragment was cloned, sequenced and the sequence
      BLAST-tested. Similarly, the ITS1 product was sequenced and BLAST-tested. The
      BLAST test results revealed that Neospora caninum DNA was present in these blood
      samples indicating that polymerase chain reaction can be used in the detection of
      N. caninum DNA in the blood of sero-positive cows.

PMID- 15262010
TI  - The sixth taste?
AB  - Five taste qualities are recognized in humans: sweet, bitter, sour, salty, and
      umami. Rats and some other species may also have a sixth taste. Behavioral and
      electrophysiological data suggest that rats can taste polysaccharides derived
      from starch. Furthermore, the tastes of sugars and polysaccharides appear to
      differ in quality. Rats also discriminate different types of polysaccharide and
      starch molecules. Recent studies indicate that sweet taste is mediated by a T1R2
      and T1R3 receptor complex but the identity of the hypothesized polysaccharide
      taste receptor remains to be established.

PMID- 15262011
TI  - Associations between oral sensation, dietary behaviors and risk of cardiovascular
      disease (CVD).
AB  - We hypothesize that variation in oral sensation influences chronic disease risk
      by impacting dietary behaviors. Bitterness of 6-n-propylthiouracil (PROP) and
      fungiform papilla (FP) number serve as genetic taste markers. Data support that
      nontasters (who taste PROP as least bitter or have lowest FP number) show dietary
      behaviors that increase CVD risk (e.g. higher alcohol intake, greater preference
      for and intake of high-fat and sweet foods) and have greater measured CVD risk
      (e.g. higher blood pressure, less favorable serum lipids). Taste genetics
      interacts with environmental factors (e.g. taste-related pathologies) to affect
      oral sensation, dietary behaviors and disease risk. The generalizability of oral
      sensory and CVD risk relationships has begun to be tested on diverse samples.

PMID- 15262012
TI  - Accumbens dopamine mediates the rewarding effect of orosensory stimulation by
      sucrose.
AB  - To investigate the hypothesis that central dopamine mediates the rewarding effect
      of orosensory stimulation by sucrose that increases eating, specific dopamine
      antagonists were administered prior to sham-feeding tests in which rats ingested
      various concentrations of sucrose. Sham feeding (SF) was used to preserve the
      orosensory stimulation of sucrose while it eliminated sucrose's postingestive
      effects. The antagonists decreased intake as a function of the concentration of
      sucrose. Microstructural analysis of licking demonstrated that the antagonists
      did not affect the motor performance of licking. Thus, the inhibitory effect of
      the antagonists on intake was due to a decrease in the rewarding effect of
      sucrose. Microdialysis experiments demonstrated that dopamine was released in the
      nucleus accumbens during SF and that the synaptic action of dopamine in the
      accumbens was necessary for the normal rewarding effect of orosensory stimulation
      by sucrose.

PMID- 15262013
TI  - Psychophysics: a journey from the laboratory to the clinic.
AB  - Pfaffmann, famous for pioneering work in taste neurophysiology, was a great
      supporter of psychophysics. He wrote: "Indeed it can be said that without
      behavioral study, hand in hand with physiological and anatomical methods, one
      gets only a partial insight: telling where, and to some degree how, but not for
      what!" [The Psychologists, 1974; Chem Senses Flavour 1 (1974) 61]. The
      psychophysical studies he initially encouraged concerned mechanism (e.g. taste
      quality coding), but later methodological advances permitted valid comparisons of
      taste sensations across groups. Quantification of genetic as well as pathological
      variation permits the demonstration of links between oral sensory variation, food
      preferences, diet and health.

PMID- 15262014
TI  - Factors influencing consumption of pork and poultry in the Irish market.
AB  - Comparisons of Irish consumers' beliefs about pork and poultry in the framework
      of Fishbein and Ajzen's Theory of Reasoned Action (TRA) showed that poultry is
      viewed as the tastier, healthier and less expensive of the two meats while pork
      is viewed as the safer meat. The influence of attitudes and important others on
      intention to consume these meats was explored and the findings support the basic
      structure of the TRA model. In this study, both attitudes towards poultry and
      pork consumption and the influence of important others influenced intention to
      consume pork and poultry, but attitude was of greater importance. For poultry,
      health, eating enjoyment, safety and price were most important determinants of
      attitude with environment and animal welfare less so. In the case of pork,
      health, eating enjoyment, safety and animal welfare were most important
      determinants of attitude with environment and price less so. Furthermore,
      doctor's advice influenced the subject norm for both poultry and pork, which in
      turn influenced intention to consume, while dietician's advice only influenced
      the subject norm for pork.

PMID- 15262015
TI  - Talking about taste: using a discursive psychological approach to examine
      challenges to food evaluations.
AB  - This study is concerned with developing the interdisciplinary nature of food
      research, and with examining eating practices as they occur in everyday
      situations. The aim is to demonstrate how discursive approaches may contribute to
      eating research using a specific analytical example. A discursive psychological
      approach is used to examine mealtime conversations from 10 families with the
      analysis focusing on how food evaluations are challenged in interaction-for
      example, asking someone to justify what they think is 'wrong' with the food. Data
      are presented with 7 examples of the 30 challenges that were found within the
      data corpus. The analysis demonstrates how people may be held accountable for
      their expressed taste preferences when being challenged, and how this contributes
      to our understanding of eating as primarily an individual and embodied
      experience. It is argued that a specific and detailed analysis of eating
      interactions provides an alternative way of conceptualising food evaluations as
      discursive rather than mentalistic concepts. A discursive approach also opens up
      practical ways in which the social and familial aspects of eating may be examined
      as they occur as part of food practices.

PMID- 15262016
TI  - Stress and eating: the effects of ego-threat and cognitive demand on food intake
      in restrained and emotional eaters.
AB  - Restrained and emotional eaters overeat in response to stress. To compare
      differential effects of cognitive demand and ego-threatening stressors on
      subsequent chocolate intake, 38 females completed a neutral (control), an ego
      threatening and an incongruent Stroop colour-naming task on three separate
      occasions. Participants were assigned to four groups based on median-split scores
      on the restrained and emotional eating scales of the Dutch Eating Behaviour
      Questionnaire-high restraint/high emotional, high restraint/low emotional, low
      restraint/high emotional and low restraint/low emotional. Higher response
      latencies were observed in the incongruent task, confirming its greater cognitive
      (attentional) demand. Overall intake was enhanced by 23% after ego-threat and 15%
      after the incongruent Stroop task relative to control. Restraint was associated
      with greater intake after both ego-threat and the incongruent task than in the
      control condition. In contrast, emotional eating was associated with greater
      intake after only the ego-threat, relative to control. A positive association
      between reaction time and subsequent intake in all conditions for high
      restraint/low emotional eaters provided support for the limited capacity
      hypothesis. Enhanced intake in emotional eaters is proposed to relate to escape
      from self-awareness. These findings demonstrate differential effects of threat
      and demand on stress-related eating in restrained and emotional eaters.

PMID- 15262017
TI  - Cognitive eating restraint scores are associated with body fatness but not with
      other measures of dieting in women.
AB  - Nearly 50% of women report dieting to lose weight, but the ability of cognitive
      eating restraint (CER) scores to separate women based on indicators of restricted
      intake has not been adequately demonstrated. We examined the ability of the CER
      subscale of the eating inventory to distinguish differences in resting energy
      expenditure (REE), body composition, cortisol, dietary intake, and physical
      activity, in a group of women. Subjects (20.4+/-2.3 years) were divided into high
      (score>9; n=31) and low (score< or =9; n=34) CER groups based on questionnaire
      responses. Indirect calorimetry was used to measure REE and dual-energy X-ray
      absorptiometry to measure body composition. Salivary and 24-hour urinary cortisol
      were measured by bioassays. Food frequency questionnaires and 4-day food records,
      physical activity recalls, and anthropometric measures were completed. Women in
      the high CER group possessed more fat mass (p<0.05) and higher body fat percent
      (p<0.05) and consumed more servings of fruits and vegetables per day (p<0.05)
      compared to women in the low CER group. Differences in other indicators were not
      observed between CER groups. Our findings suggest that cognitive restraint and
      body fatness may not be independent of one another.

PMID- 15262018
TI  - Predicting intentions to consume functional foods and supplements to offset
      memory loss using an adaptation of protection motivation theory.
AB  - The widespread use of dietary supplements and so-called 'functional foods' is
      thought to be partially motivated by self-control of health. However, whilst
      consumers want foods associated with well-being or disease prevention, they are
      unlikely to be willing to compromise on taste or technology. This presents a
      dilemma for promoters of functional foods. Middle-aged consumers' intentions to
      consume functional foods or supplements that may improve memory were tested
      within an adaptation of Protection Motivation theory (PMT). Participants
      evaluated text descriptions of four products described as: having an unpleasant
      bitter taste (Natural-FF); having 'additives' to reduce bitterness (Sweetened
      FF); being genetically modified to enhance function (GM-FF) and Supplements.
      Participants were recruited as being of high and low perceived vulnerability to
      memory failure. In total, 290 middle-aged consumers (aged 40-60 years)
      participated in the study. Motivations to consume the GM-FF were the lowest.
      There were gender differences between intention to consume the supplements,
      Natural-FF and Sweetened-FF and product differences within genders. Women were
      less favourable than men in their attitudes towards genetic modification in
      general. Regression analyses indicated that PM predictors of intention to consume
      functional foods or supplements explained 59-63% of the variance (R2). Overall,
      perceived 'efficacy' (of the behaviour) and self-efficacy were the most important
      predictors of intentions to consume.

PMID- 15262019
TI  - Magical food and health beliefs: a portrait of believers and functions of the
      beliefs.
AB  - The aims of the present two studies were to delineate a portrait of people who
      are attracted to magical beliefs about food and health and to study the self
      reported functions for the beliefs. Participants were Finnish men and women
      ranging in age from 15 to 66 years (N=3261 in study 1 and N=189 in study 2), and
      they filled in either an Internet-based or a paper questionnaire. The believers
      were more often women than men, vegetarians than omnivores, and they relied more
      on alternative medicine, thought in a more intuitive way, and demonstrated more
      eating-disordered thinking than the nonbelievers. Additionally, the believers had
      experienced slightly more negative life events than the nonbelievers in study 1
      but contrary to our hypothesis, they did not differ in their desire for control.
      The believers reported value-expressive function as the most important one served
      by their beliefs, followed by the control and utilitarian functions. The
      emotional, intuitive nature of food beliefs and their connection to values and
      identity are discussed.

PMID- 15262020
TI  - Willingness to try new foods as predicted by social representations and attitude
      and trait scales.
AB  - The structure and predictive ability of social representation of new foods were
      investigated and compared with instruments measuring relevant attitudes and
      traits using a questionnaire quantifying these aspects, completed by 743
      respondents. Based on their rated willingness to try, new foods were categorized
      as modified dairy products, genetically modified (GM), organic, and ethnic
      products (two examples, snails and passion fruit, were treated separately). The
      social representation (SR) consisted of five dimensions: suspicion of novelties,
      adherence to technology, adherence to natural food, eating as an enjoyment, and
      eating as a necessity. The SR dimensions were strong predictors of willingness to
      try GM foods (predicted by adherence to technology) and organic foods (predicted
      by adherence to natural foods). Low food neophobia predicted the rated
      willingness to try snails and passion fruit. Thus, different constructs predicted
      willingness to try different categories of new foods, and as a whole, SR
      dimensions markedly improved the prediction.

PMID- 15262021
TI  - Use of conjoint analysis to assess web-based communications on functional foods.
AB  - This paper reports the results of conjoint analysis of communications about
      functional foods, run with women aged 40 and above, using messages found on the
      Internet. Each of 147 women evaluated 60 concepts, comprising 2-4 phrases per
      concept, with the phrases dealing with an aspect of functional foods. Three
      respondent segments emerged, based on the pattern of individual utilities,
      'health optimists' (no deep interest in functional foods), 'food for life' (food
      for health), and 'food for cure' (looking to functional foods to help live a
      normal life). The utilities of the same elements differed far more across these
      segments than would be expected from conventional classification questionnaires.

PMID- 15262022
TI  - Influence of mother's educational level on food parenting practices and food
      habits of young children.
AB  - The main purpose of the present study is to examine whether differences in
      mothers' food parenting practices by educational level could explain differences
      in food consumption in Flemish preschool children. Three hundred and sixteen
      mothers of children aged 2.5-7 years, completed a self-administered
      questionnaire. Differences by educational level were found in children's and
      mothers' consumption frequencies of fruit, vegetables and soft drinks, and in the
      use of restrictions, verbal praise, negotiation, discouragement of sweets and
      restraining from negative modelling behaviour. Multiple logistic regression
      analyses revealed that mothers' consumption was an independent predictor for all
      four outcome variables; verbal praise was a significant predictor for children's
      vegetable consumption, permissiveness for regular consumption of soft drinks and
      sweets, and, using food as a reward for regular sweet consumption. Differences in
      children's food consumption by mothers' educational level were completely
      explained by mother's consumption and other food parenting practices for fruit
      and vegetables but not for soft drinks.

PMID- 15262023
TI  - Suspicious minds: perceived vitamin content of ordinary and diet foods with added
      fat, sugar or salt.
AB  - Male and female dieters and non-dieters (mean age 18.5 years) rated the vitamin
      levels of ordinary foods (e.g. 'sliced fresh peaches') and counterparts with
      added fat, sugar or salt (e.g. 'sliced fresh peaches with sugar'). Unlike
      previous studies, in addition diet foods ('sugar-free ice cream') were compared
      to their ordinary fat- and/or sugar-rich counterparts ('ice cream'). Some
      respondents believed diet products to be lower in vitamins, particularly when the
      corresponding ordinary food was considered to be wholesome (e.g. milk or
      muffins).

PMID- 15262024
TI  - The role of coronary endothelial function testing in patients suspected for
      angina pectoris.
AB  - Coronary vasomotor function plays an important role in onset and progression of
      coronary artery disease. Suwaidi [Circulation 101 (2000) 948] and Schachinger
      [Circulation 101 (2000) 1899] demonstrated that vasomotor dysfunction has a
      significant impact on events in patients with minimal coronary artery disease.
      Endothelial specific testing can be performed in coronary as well as peripheral
      arteries. However, non-coronary tests have a low correlation with the coronary
      vasomotor response, as assessed by acetylcholine. In large clinical prospective
      placebo-controlled trials, angiotensin-converting enzyme (ACE) inhibitors and
      lipid-lowering drugs reduce morbidity and mortality after myocardial infarction
      or myocardial infarction-induced heart failure. The same drugs restore
      endothelial dysfunction after myocardial infarction, as was demonstrated in small
      experimental and clinical studies. Recent studies in patients with coronary
      artery disease showed a relation with endothelial dysfunction and the occurrence
      of adverse coronary events. For this reason, it is important to develop methods
      to evaluate endothelial function.

PMID- 15262025
TI  - Does aggressive statin therapy offer improved cholesterol-independent benefits
      compared to conventional statin treatment?
AB  - There is currently intense research interest in the properties of HMG-CoA
      reductase inhibitors (statins) beyond their well-documented lipid-lowering
      action. Studies have consistently demonstrated that administration of statin
      therapy decreases levels of the inflammatory marker C-reactive protein (CRP), a
      marker associated with an increased risk of cardiovascular events. This effect
      appears to be independent of the extent of reduction in total or LDL-cholesterol.
      Statins also appear to improve endothelial dysfunction by increasing endothelium
      dependent vasodilatation. There is also evidence that statins inhibit fibrin
      formation and thrombus development, an effect that which would be clinically
      beneficial following plaque fissure or rupture. Early preclinical and clinical
      evidence suggests that there are quantitative differences between statin regimens
      in terms of their cholesterol-independent properties. Trials comparing equipotent
      doses of different statins, based on lipid-lowering efficacy, have not reported
      any differences in cholesterol-independent properties. However, the current
      evidence base indicates that more aggressive statin regimens are associated with
      an enhanced anti-inflammatory effect. Intensive lipid-lowering using statin
      therapy generates a greater reduction in mortality than standard lipid
      management, and it is possible that enhanced cholesterol-independent effects may
      account for some of this excess benefit.

PMID- 15262026
TI  - Improving the acceptability of the atrial defibrillator for the treatment of
      persistent atrial fibrillation: the atrial defibrillator sedation assessment
      study (ADSAS).
AB  - BACKGROUND: To compare the acceptability and effectiveness of three pre
      medication regimens for manually activated cardioversion of recurrent persistent
      atrial fibrillation. METHODS: Eighteen patients implanted with the Jewel AF
      atrial defibrillator for drug-resistant persistent atrial fibrillation only were
      studied in an open-labelled randomised crossover study. Patients were assigned to
      sedation (S) with midazolam elixir, analgesia (A) with morphine sulphate or
      combination therapy (C) with dextromoramide and lorazepam. Pre-medication was
      taken up to 1 h before cardioversion. Patients rotated through each type of
      medication after undertaking at least one cardioversion. Visual analogue scales
      were completed immediately post-cardioversion and 24 h later for pain, anxiety
      and 'unpleasantness'. Higher scores represented a worse outcome. RESULTS: After 2
      years' follow-up, 238 cardioversions were performed with S, 17 with A and 35 with
      C. The mean immediate combined score for S (10.9, 95% confidence interval (CI)
      8.2-13.6) was significantly lower than for A (17.3, 95% CI 15.1-19.5, P = 0.01)
      and for C (15.9, 95% CI 12.3-19.6, P = 0.02). All patients who used S chose it as
      the most favourable pre-medicant. All patients who used A found it the least
      acceptable. CONCLUSION: Sedation rather than analgesia enhanced the acceptability
      of manually activated atrial defibrillation.

PMID- 15262027
TI  - Hepatitis C and the heart: to beat or not to beat.
AB  - BACKGROUND: Many enteroviruses as well as hepatitis C have been increasingly
      found in association with cardiomyopathies, even though, the evidence has been
      inconclusive. METHODS: From 1998 to 2001, at the liver clinic of our community
      based hospital, in the cohort of hepatitis C patients, infection evidence by PCR
      confirmation and echocardiographic measures of left ventricular (LV) function
      were obtained. RESULTS: One hundred-eight patients were identified. Fifty percent
      of them have echocardiographic abnormalities. Patient's mean age was 55 +/- 10
      years; 45% women, 55% men; 32% had LVH, 13.8% had high right ventricular systolic
      pressures, and 4% displayed contractility abnormalities. No cases of dilated or
      hypertrophic cardiomiopathies were found. CONCLUSIONS: Echocardiographic
      abnormalities are not uncommon findings associated with hepatitis C infection,
      however all these findings can easily be explained by existing co-morbidities.
      High right ventricular systolic pressure, suggestive of pulmonary hypertension,
      which may be secondary to portal hypertension, is an independent finding for
      hepatitis C.

PMID- 15262028
TI  - Can enoxaparin safely replace unfractionated heparin during coronary intervention
      in acute coronary syndromes?
AB  - BACKGROUND: Enoxaparin has gained wide acceptance in patients with acute coronary
      syndromes. However, there is uncertainty regarding management of patients who
      require coronary intervention while on enoxaparin. Some physicians withhold the
      morning dose of enoxaparin prior to coronary intervention while others switch
      patients to unfractionated heparin. Both methods do not provide optimal
      anticoagulation in the hours preceding intervention. There are no published
      controlled data to assess the safety of coronary intervention using enoxaparin
      alone in patients with acute coronary syndromes. METHODS: We prospectively
      compared enoxaparin to unfractionated heparin during coronary angiography and
      intervention. Sixty four patients admitted to the coronary care unit (CCU) were
      given enoxaparin twice daily, including on the morning of procedure. Coronary
      angiography and intervention were performed without additional unfractionated
      heparin. The control group comprised of 52 patients admitted to Internal Medicine
      for an acute coronary syndrome. These were also given enoxaparin but the morning
      dose was withheld and unfractionated heparin was used during procedure. RESULTS:
      Patients in both groups had similar baseline characteristics. No significant
      differences were observed between the two groups in procedural success rate,
      complications or bleeding. One year follow up showed similar rates of
      hospitalization and mortality. CONCLUSION: Enoxaparin seems to offer safe and
      effective procedural anticoagulation in patients undergoing percutaneous
      intervention for acute coronary syndromes. Patients given enoxaparin can probably
      have coronary intervention without interruption of enoxaparin treatment and
      without additional procedural anticoagulation. These findings require
      confirmation in larger, randomized trials.

PMID- 15262029
TI  - Association between urokinase-plasminogen activator gene T4065C polymorphism and
      risk of mitral valve prolapse.
AB  - BACKGROUND: Abnormalities of collagen and elastic fibers were found in floppy
      mitral valves (FMV). Urokinase-plasminogen activator (PLAU) was suggested to be
      involved in the pathogenesis of elastin and collagen degradation in arterial
      aneurysm. The role of PLAU genetic variant in mitral valve prolapse (MVP) has not
      been studied. We, therefore, performed a case-controlled study investigating the
      possible relation between the PLAU gene polymorphisms and risk of MVP in Taiwan
      Chinese. METHODS: We studied 100 patients with MVP diagnosed by echocardiography
      and 106 age- and sex-matched normal control subjects. The T4065C and T3995C
      polymorphisms of the PLAU gene were identified by polymerase chain reaction (PCR)
      based restriction analysis. RESULTS: There was a significant difference in either
      the genotype distribution or allelic frequencies between MVP cases and controls
      for PLAU gene T4065C polymorphism (P = 0.0001 and 0.0002, respectively). An odds
      ratio for risk of MVP associated with PLAU T4065C TC genotype was 6.03 (95%
      confidence interval 2.11-14.83). An odds ratio for risk of MVP associated with
      PLAU T4065C T allele was 4.99 (95% confidence interval 1.93-12.91). There was no
      significant difference in either the genotype distribution or allelic frequencies
      between MVP cases and controls for PLAU T3995C polymorphism. Further
      categorization of the MVP patients into mild and severe subgroups revealed no
      statistical difference between these two subgroups for PLAU T4065C and T3995C
      polymorphisms. CONCLUSIONS: This study shows that patients with MVP have a higher
      frequency of PLAU T4065C TC genotype and T allele that supports a role of the
      PLAU T4065C polymorphism in determining the risk of MVP among the Chinese
      population in Taiwan.

PMID- 15262030
TI  - Effects of sinus rhythm restoration in patients with persistent atrial
      fibrillation: a clinical, echocardiographic and hormonal study.
AB  - The hemodynamic consequences of atrial fibrillation (AF) may lead to impairment
      of the left ventricular function and a reduction in exercise capacity. Studies on
      mechanical and neurohormonal remodelling in patients with AF are becoming
      increasingly important. The results could possibly enhance treatment strategies
      of these patients. The aim of this study was to assess changes in exercise
      capacity, echocardiographic findings and plasma atrial natriuretic peptide (ANP)
      concentrations in patients with non-rheumatic persistent AF, before and 30 days
      after successful cardioversion. METHODS: We attempted cardioversion in 42
      consecutive patients, aged 58 +/- 8 years, with persistent non-valvular AF of
      duration 7.1 +/- 7.1 months. They underwent echocardiography examination and
      submaximal exercise testing 24 h before and 30 days after cardioversion. Exercise
      capacity was determined during symptom-limited exercise testing, according to a
      modified Bruce protocol with peak VO2 analysis. Plasma samples of ANP were
      obtained at rest: before, the day after, and 30 days after cardioversion therapy,
      and were prepared by refrigerated centrifugation and stored until
      radioimmunoassay. The control study group, without AF, comprised of 11 subjects.
      RESULTS: Cardioversion was successful in 35 patients. However, in six of the 35
      patients, AF reappeared within 1 month. There were no statistical differences
      before cardioversion in exercise tolerance and ejection fraction of left
      ventricle between the group with successful cardioversion and the group with
      unsuccessful cardioversion or with recurrence of AF. On the 30th day after
      cardioversion we recorded a significant increase in exercise tolerance: duration
      of exercise 13.7 +/- 3.2 versus 9.5 +/- 3.4 min, (P < 0.05); peak oxygen
      consumption 32.2 +/- 3.6 versus 19.85 +/- 3.5 ml/min per kg, (P < 0.05); and
      ejection fraction of left ventricle 58.6 +/- 9.4 versus 52.7 +/- 10.2% (P <
      0.05); in the sinus rhythm group. There was no significant improvement observed
      in the AF group. The mean baseline ANP level was 58.5 +/- 15.7 pg/ml in the study
      group and 34.3 +/- 10.2 pg/ml in the control group (P < 0.01). The successful
      therapy reduced significantly the pretreatment mean plasma ANP concentration from
      58.5 +/- 15.7 to 31.4 +/- 15.0 pg/ml, (P < 0.01); the day after cardioversion, in
      the group of 35 patients. It remained stable for the next 30 days (36.9 +/- 15.2
      pg/ml) in the group of 29 patients who remained in sinus rhythm, and increased to
      53.4 +/- 16.4 pg/ml in the group of six patients who had recurrence of AF. Plasma
      ANP did not change in the group of seven patients with unsuccessful
      cardioversion. CONCLUSIONS: The restoration of sinus rhythm in patients with
      persistent AF was associated with a significant improvement in cardiac
      performance and exercise tolerance 1 month after cardioversion. Such improvement
      was not observed in the group with unsuccessful cardioversion or with AF
      recurrence. The plasma ANP concentration in patients with AF was significantly
      reduced after successful cardioversion and remained stable for a period of 30
      days.

PMID- 15262031
TI  - Is B-type natriuretic peptide-guided heart failure management cost-effective?
AB  - BACKGROUND: Chronic heart failure (CHF) is a common medical problem and B-type
      natriuretic peptide (BNP)-guided heart failure management for outpatients with
      symptomatic CHF was found to reduce the readmission rate and mortality, but the
      costs of treatment may provoke concern in the current cost-conscious clinical
      setting. METHODS: We conducted a cost-effectiveness analysis using a Markov model
      of regular BNP measurement in the outpatient setting. The target population was
      symptomatic CHF patients aged 35-85 years recently discharged from the hospital.
      Intervention was BNP measurement once every 3 months (BNP group) or no BNP
      measurement (clinical group). Clinical and utility data were retrieved from
      published studies. Costs were based on published data in the US. Cost
      effectiveness was measured by $ per quality-adjusted life year (QALY). RESULTS:
      The baseline analysis during the 9-month period after hospitalization showed the
      QALY to be longer for the BNP group (0.57 for the BNP group and 0.55 for the
      clinical group) and the costs were also lower for the BNP group ($9577 and
      10,131). The dominance of the BNP group continued during the 1-year follow-up.
      The incremental costs would be $3491-7787 per QALY. In sensitivity analyses, two
      parameters with strong effects on the cost-effectiveness were the probability of
      the first readmission for CHF in the clinical group and the costs for inpatient
      CHF care. When these two parameters were simultaneously put on the simulation
      model, the incremental costs of the BNP group may exceed $50,000. CONCLUSIONS:
      Introduction of BNP measurement in heart failure management may be cost
      effective.

PMID- 15262032
TI  - A modified and unifying neurogenic hypothesis can explain the natural history of
      chronic Chagas heart disease.
AB  - The pathogenesis of chronic Chagas disease still is an unresolved and
      controversial issue. Parasite persistence and autoimmune responses cannot explain
      the spectrum of chronic Chagas disease. However, a modified neurogenic
      hypothesis, concerning the timing and mechanisms responsible for the cardiac
      parasympathetic damage and for the activation of the sympathetic nervous system
      and of other neurohormonal systems, unifies cardiac remodelling and neurohormonal
      activation to explain most of the events of the natural history of Chagas
      disease.

PMID- 15262033
TI  - Evidence for left ventricular remodeling after percutaneous coronary
      intervention: effect of percutaneous coronary intervention on left ventricular
      ejection fraction and volumes.
AB  - BACKGROUND: Post-stress ejection fraction (EF), end-diastolic (EDV) and end
      systolic (ESV) volumes by gated myocardial perfusion SPECT (MPS) are well
      validated, reproducible and of prognostic significance. However, little is known
      about the impact of percutaneous coronary intervention (PCI) on left ventricular
      volumes and remodeling. METHODS: Thirty-eight patients who underwent MPS before
      and 6 months after PCI were evaluated. MPS were interpreted deriving summed
      stress (SSS), rest (SRS) and difference (SDS = SSS-SRS; extent of ischemia)
      scores. EF, EDV and ESV were generated by QGS trade mark. Pre-PCI MPS were
      compared to post-PCI MPS. RESULTS: Single vessel disease was present in 63% of
      patients. PCI of one vessel was performed in 82% of patients. After 6 months, SSS
      (10.6 +/- 6.3 vs. 2.8 +/- 4.3, p < 0.001) and SDS (8.2 +/- 5.6 vs. 1.4 +/- 2.3, p
      < 0.001) had improved; however, EF did not change significantly (55 +/- 10 vs. 57
      +/- 13, p = ns). Still, EDV (105 +/- 25 ml vs. 96 +/- 25 ml, p = 0.006) and ESV
      (49 +/- 19 ml vs. 41 +/- 18 ml, p = 0.001) were significantly reduced.
      CONCLUSION: Results of MPS documented the beneficial effect of PCI on symptoms
      and extent of ischemia. In addition, the findings showed a significant decrease
      in ESV and EDV after PCI as compared to pre-PCI findings which points to a
      positive effect on left ventricular remodeling even in the absence of significant
      changes in EF.

PMID- 15262034
TI  - The province of Alberta, Canada avoids the hospitalization epidemic for
      congestive heart failure patients.
AB  - BACKGROUND: We assessed the incidence and prevalence of congestive heart failure
      (CHF) in patients diagnosed at the time of hospitalization and patients diagnosed
      in specialists offices without prior hospitalization in order to compare the
      trends in Canada with previously published trends in the USA and other
      industrialized countries. METHODS: Administrative data for Alberta, Canada from 1
      April 1994 to 31 March 2000. RESULTS: There was a small but statistically
      significant decline in the age-sex incident and prevalent hospitalization rates
      for CHF between 1994/1995 (incidence per 1000 of 1.59; 99% CI 1.51, 1.66:
      prevalence per 1000 of 2.31; 99% CI 2.22, 2.40) and the year 1999/2000 (incidence
      per 1000 of 1.24; 99% CI 1.18, 1.30: prevalence per 1000 of 1.97; 99% CI 1.89,
      2.05). Crude hospitalization rate per 1000 also demonstrated a small but
      statistically significant decline between 1994/1995 (2.98; 99% CI 2.88, 3.08) and
      1999/2000 (2.55; 99% CI 2.46, 2.64). The age-sex incident rates of ambulatory
      diagnosis of CHF were similar throughout the 1994/1995-1999/2000 time period
      (0.88; 99% CI 0.82, 0.94 during 1994/1995 and 0.84; 99% CI 0.79, 0.89 during
      1999/2000). The crude mortality percentage for incident hospitalization for CHF
      were similar throughout the 1994/1995-1999/2000 time period (31.0%; 99% CI 28.7,
      33.3 during 1994/1995 and 28.6%; 99% CI 26.3, 30.9 during 1999/2000).
      CONCLUSIONS: We noted a small decrease in the incident, prevalent, and total
      hospitalizations for CHF in the time period 1994/1995-1999/2000. The decrease was
      not the result of a substituted increase in ambulatory diagnosis for CHF.

PMID- 15262035
TI  - Survey of specialized tertiary care facilities for adults with congenital heart
      disease.
AB  - BACKGROUND: Specialized tertiary care facilities developed in response to the
      increasing numbers of adults with congenital heart disease (CHD). Because this
      patient population comprises a relatively new area of specialized cardiovascular
      interest, the first facilities necessarily evolved without preexisting guidelines
      or interaction. OBJECTIVES: To characterize the major features of the six
      original and largest tertiary adults CHD facilities. METHODS: Written
      questionnaire sent to six participating facilities in North America and Europe.
      Information was analyzed centrally. RESULTS: All but one facilities was
      established over 20 years ago, and each cares for over 1500 patients. Hospital
      admissions ranged from 100 to 660 patients/unit/year. Of the total number of
      registered patients, 52-81% had undergone one or more reparative surgeries.
      Reoperations constituted 25-80% of the 50-170 operations/unit/year. Overall mean
      surgical mortality was 1.9%/year. Inpatient and outpatient care was provided in
      adult (n = 4) or both adult and pediatric (n = 2) settings. All six facilities
      enjoyed close collaboration between adult and pediatric cardiologists, cardiac
      surgeons, nurse specialists and cardiac and non-cardiac consultants. Training and
      research were pivotal activities. CONCLUSIONS: Provision of comprehensive care by
      multidisciplinary teams including adult and pediatric cardiologists, cardiac
      surgeons, specialized nurses and other cardiac and non-cardiac consultants was
      the unifying feature for all six tertiary care facilities reported here. There
      were minor differences among them based on available resources, local expertise
      and national health care policies. There appears to be a significant shortfall in
      tertiary care provision for the adult with CHD that requires further planning and
      resource allocation. These data may be useful for new and evolving adult CHD
      services.

PMID- 15262036
TI  - Does hospitalization for congestive heart failure occur more frequently in
      Ramadan: a population-based study (1991-2001).
AB  - OBJECTIVE: Over one billion Muslims fast worldwide during the month of Ramadan.
      Fasting during Ramadan is essentially a radical change in lifestyle for the
      period of one lunar month, so it is important to see the response of congestive
      heart failure patients to this change. Our objective in this study is to
      investigate whether Ramadan fasting has any effect on the number of
      hospitalization for congestive heart failure (CHF) in a geographically defined
      population. METHODS: We conducted a retrospective review of clinical data study
      on all Qatari patients in Qatar for a period of 10 years (January 1991 through
      December 2001) who were hospitalized with heart failure. Patients were divided
      according to the time of presentation in relation to the month of Ramadan, 1
      month before, during and 1 month after Ramadan. The number of hospitalization for
      CHF in various time periods was analyzed. The age of presentation, gender,
      cardiovascular risk factor profiles (smoking status, hypertension,
      hypercholesterolemia, diabetes, pre-existing coronary heart disease) and outcome
      were analyzed. RESULTS: Of the 20,856 patients treated during the 10-year period,
      8446 of them were Qataris with 5095 males and 3351 females. Overall, 2160 Qatari
      patients were hospitalized for CHF and their mean age and standard deviation was
      64.2 +/- 11.5 years, 52.4% were hypertensives, 18.5% had hypercholestrolemia,
      17.7% were current smokers and 56.5% were diabetics. The overall mortality was
      9.7%. The number of hospitalization for CHF was not significantly different in
      Ramadan (208 cases) when compared to a month before Ramadan (182 cases) and a
      month after Ramadan (198 cases); p > 0.37). There was no significant difference
      found in the baseline clinical characteristics or mortality (11.5%, 7.7% and
      9.6%, respectively; p > 0.43) in patients presenting in various time periods.
      CONCLUSION: This population-based study demonstrates that no significant
      difference was found in number of hospitalization for CHF while fasting in
      Ramadan when compared to the non-fasting months.

PMID- 15262037
TI  - 17beta-estradiol preserves endothelial function by reduction of the endogenous
      nitric oxide synthase inhibitor level.
AB  - Previous studies have shown that endothelial dysfunction is associated to an
      increase of endogenous nitric oxide synthase (NOS) inhibitor level and estrogen
      reduces impairment of the endothelium due to oxidized low-density lipoprotein
      (LDL). The purpose of the present study was to investigate the effect of
      estradiol on endothelial dysfunction and the increased level of asymmetric
      dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, induced
      by LDL. Male Sprague-Dawley rats were treated with a single injection of native
      LDL (4 mg/kg) for 48 h. Vasodilator responses to acetylcholine in the aortic
      rings and serum levels of ADMA and malondialdehyde (MDA) were determined.
      Treatment with native LDL markedly reduced endothelium-dependent relaxation to
      acetylcholine in the isolated rat thoracic aortic rings and increased serum
      levels of ADMA and MDA (P < 0.01). Pretreatment with 17beta-estradiol (0.1 or 0.3
      mg/kg) significantly attenuated inhibition of vasodilator responses to
      acetylcholine and elevation of both ADMA and MDA concentration by LDL (P < 0.01).
      These results suggest that estradiol possesses a protective effect on the
      endothelium and the protective effect is related to reduction of ADMA
      concentration by inhibition of lipid peroxidation.

PMID- 15262038
TI  - Utilization of eptifibatide for treatment of severe dissections as a bail-out
      procedure.
AB  - BACKGROUND: It has been shown in several large trials that the inhibition of
      glycoprotein (GP) IIb/IIIa receptors of platelets can reduce the rate of ischemic
      complications following percutaneous transluminal coronary angioplasty (PTCA). We
      sought to determine the efficacy of eptifibatide in patients with severe
      dissections or threatened vessel closure after PTCA in small coronary arteries (<
      2.5 mm). METHODS: Eptifibatide was used in 51 patients after conventional balloon
      angioplasty complicated by severe dissections with or without threatened vessel
      occlusion. Eptifibatide was administered as a double-bolus of 180 microg/kg
      bodyweight, followed by a continuous infusion at a dosage of 2.0 microg/kg min
      over a time period of 20 h. In this situation, the implantation of a coronary
      stent was avoided if a prompt antegrade flow of contrast dye could be maintained.
      RESULTS: Using the GP IIb/IIIa antagonist eptifibatide, it was possible to
      increase or to maintain antegrade blood flow in 28 (55%) patients. In 45% of the
      patient population, however, repeat PTCA was needed, and in four patients (7.8%)
      an intracoronary stent had to be implanted. During hospitalization three (6%)
      patients underwent target lesion revascularization (two Re-PTCAs, one coronary
      bypass graft operation). There were no myocardial infarctions and there was no
      intrahospital death. The cumulative event rate including acute and long term
      events was 25%. CONCLUSIONS: The findings of our study indicate that eptifibatide
      is able to prevent vessel occlusion after PTCA complicated by severe dissections
      with or without threatened vessel occlusion associated with a low-in-hospital
      complication rate.

PMID- 15262039
TI  - Levels of soluble adhesion molecules in various clinical presentations of
      coronary atherosclerosis.
AB  - Adhesion molecules play an important role in the development and course of
      coronary atherosclerosis. In this study, soluble forms of vascular cell adhesion
      molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1), E-selectin and P
      selectin were evaluated in patients with various clinical presentations of
      coronary atherosclerosis and compared them to those with angiographically
      documented normal coronary arteries. Venous plasma samples were collected from 43
      patients with acute myocardial infarction (AMI), 45 with unstable angina pectoris
      (UAP), 34 with stable angina pectoris (SAP) and 29 subjects with normal coronary
      arteries (control). The VCAM-1 level was significantly higher in patients with
      AMI (mean +/- SEM; 799.8 +/- 26.3 ng/ml) than those with UAP (644.2 +/- 26.7
      ng/ml) and SAP (526 +/- 32.5 ng/ml) and controls (270 +/- 26.8 ng/ml). In
      patients with UAP, VCAM-1 was found to be significantly elevated as compared to
      the SAP group and controls. VCAM-1 level was also higher in SAP group than the
      controls. Serum levels ICAM-1 were similar among patients with AMI (424.1 +/-
      15.2 ng/ml), UAP (403 +/- 12.3 ng/ml) and SAP (381.2 +/- 16.2 ng/ml); however,
      levels of ICAM-1 was significantly elevated in these groups as compared to the
      controls (244.3 +/- 11). The mean level of E-selectin was not different in AMI
      and UAP groups (47.2 +/- 2.2 vs. 42.6 +/- 2.1 ng/ml; respectively). However, it
      was significantly higher in acute coronary syndrome groups as compared to SAP
      (33.4 +/- 2.3 ng/ml) and control subjects (30.7 +/- 1.9 ng/ml). Serum levels of E
      selectin were similar in SAP group and controls. For P-selectin, no significant
      difference was observed between AMI and UAP groups (187.5 +/- 7.2 vs. 181.7 +/-
      4.7 ng/ml; respectively), however, it was significantly higher in both groups as
      compared to SAP group (146.1 +/- 7.4 ng/ml) and controls (108 +/- 6.6 ng/ml).
      Serum level of P-selectin was significantly higher in patients with SAP than the
      control group. In conclusion, determination of serum VCAM-1, E-selectin and P
      selectin levels seems more useful for detecting coronary plaque destabilization.

PMID- 15262040
TI  - Effect of age on atrial contribution to ventricular filling after balloon mitral
      valvuloplasty in mitral stenosis.
AB  - OBJECTIVE: Ventricular filling takes place during the conduit and pump functions
      of the atrium. While studying whether relief of mitral valve obstruction improves
      atrial filling, the effect of age on atrial contribution to ventricular filling
      was studied before and after balloon mitral valvuloplasty (BMV) and on follow-up
      at 1 year. METHODS: Patients with mitral stenosis (MS) and sinus rhythm (n = 59)
      were divided into group I (< 18 years, n = 13), group II (< 30 years, n = 29) and
      group III (> 30 years, n = 17). Two-dimensional mitral valve area (MVA in cm2),
      transmitral mean gradient (MG in mm Hg), velocity time integral (VTI in cm) of
      mitral valve flow, VTI contributed by atrial systole (A-VTI), difference between
      total VTI and A-VTI (E-VTI), percentage contribution of A-VTI to the total VTI (A
      %) and difference between A-% before and after BMV (delta-A-%) were noted. Follow
      up data was obtained at 1 year. The change in A-% at follow-up (A-%-FU) was
      calculated as the difference between A-% before BMV and A-% at follow-up.
      RESULTS: There was a similar increase in MVA with a reduction in MG among the
      three groups. Among the three groups, total VTI and E-VTI before and after BMV
      were similar. Before BMV, in all the groups, A-VTI and A-% were similar. After
      BMV, there was increase in A-VTI and A-% in all the groups with a trend to be
      more in younger patients. A-VTI was significantly higher in group I only. But E
      VTI had decreased significantly in all groups and tended to be less in younger
      patients. In younger patients, delta-A-% after BMV was significantly higher (13.2
      +/- 7.6, 7.9 +/- 5.1 and 6.5 +/- 4.5, respectively, in groups I, II and III; p <
      0.01). Correlation coefficient of age against delta-A-% was -0.55 (p < 0.01).
      Correlation coefficients of delta-A-% against post-BMV-MVA and MG were not good.
      At follow-up of 11.3+/-1.2 months, changes achieved in total VTI, A-VTI, E-VTI
      and A-% were maintained. Total VTI, A-VTI, E-VTI and A-% were similar at the time
      of follow-up on comparing the three groups. But younger patients had
      significantly higher A-%-FU (12.1 +/- 5.8, 9.4 +/- 4.6 and 7.3 +/- 3.1,
      respectively, in groups I, II and III; p < 0.01). CONCLUSIONS: Prior to BMV,
      there is an age related reduction in atrial contribution to ventricular filling
      that improves with relief of MS. Advancing age reduces the immediate and late
      recovery of atrial contribution after BMV. This may be due to increasing left
      atrial fibrosis with age that prevents an improvement in atrial pump function.
      The differential improvement in atrial function in younger patients warrants
      earlier intervention in MS to achieve better recovery of atrial function.

PMID- 15262041
TI  - Intermittent hypoxia increases exercise tolerance in elderly men with and without
      coronary artery disease.
AB  - BACKGROUND: Intermittent hypoxia has been suggested to increase exercise
      tolerance by enhancing stress resistance and improving oxygen delivery. Because
      the improvement of exercise tolerance reduces mortality in the elderly with and
      without coronary artery disease intermittent hypoxia might be a valuable
      preventive and therapeutic tool. However, controlled studies are lacking. METHODS
      AND RESULTS: Sixteen males (50-70 years, 8 with and 8 without prior myocardial
      infarction) were randomly assigned in a double-blind fashion to receive 15
      sessions of passive intermittent hypoxia (hypoxia group) or normoxia (control
      group) within 3 weeks. For the hypoxia group each session consisted of three to
      five hypoxic (14-10% oxygen) periods (3-5 min) with 3-min normoxic intervals.
      Controls inhaled only normoxic air in the same way. Exercise tests were performed
      before and after the 3-week breathing program. After 3 weeks of intermittent
      hypoxia peak oxygen consumption had increased compared to normoxic conditions (+
      6.2% vs.-3%, p < 0.001). This improvement was closely related to the enhanced
      arterial oxygen content after hypoxia (r = 0.9, p < 0.001). Both higher
      haemoglobin concentration and less arterial oxygen desaturation during exercise
      contributed to the increase in arterial oxygen content. During sub-maximal
      exercise (cycling at 1 W/kg) heart rate, systolic blood pressure, blood lactate
      concentration, and the rating of perceived exertion were diminished after
      intermittent hypoxia compared to control conditions (all p < 0.05). Changes in
      responses to exercise after intermittent hypoxia were similar in subjects with
      and without prior myocardial infarction. CONCLUSIONS: Three weeks of passive
      short-term intermittent hypoxic exposures increased aerobic capacity and exercise
      tolerance in elderly men with and without coronary artery disease.

PMID- 15262042
TI  - The use of a hydrophilic-coated catheter during transradial cardiac
      catheterization is associated with a low incidence of radial artery spasm.
AB  - BACKGROUND: Radial artery spasm (RAS) is a common complication of transradial
      approach (TRA) to percutaneous coronary angiography (CAG) and coronary
      intervention. Lower friction resistance between catheter and RA wall may reduce
      RAS upon insertion, manipulation, and withdrawal of the catheter. The aim of this
      study was to investigate whether the use of a hydrophilic-coated (HC) catheter,
      which has lower friction coefficient, could reduce the incidence of RAS compared
      with a non-hydrophilic-coated (NHC) catheter. METHODS: A total 250 patients
      attempted diagnostic CAG using 5-French catheters via the TRA between September
      2000 and April 2002. Two hundred thirty-four (93.6%) patients who achieved
      successful coronary cannulation were selected for the study. NHC catheters were
      used in 149 patients (63.7%), and HC catheters were used in 85 patients (36.3%).
      We compared the incidence of RAS between NHC and HC catheters. RESULTS: RAS
      occurred in 17 (7%) patients totally. RAS was less likely to occur in HC group
      (one patient, 1%) than in the NHC group (16 patients, 11%, P = 0.007).
      CONCLUSIONS: We conclude that the use of HC catheters can reduce RAS upon
      insertion, manipulation, and withdrawal of the catheter compared with NHC
      catheters.

PMID- 15262043
TI  - Takayasu's arteritis: results of a university hospital of 45 patients in Turkey.
AB  - BACKGROUND: Takayasu's arteritis (TA) is a rare disease which appears to be most
      common in East Asia. However, the disease has been reported to be worldwide. The
      clinical features of the disease can show variations in different geographical
      areas. The aim of this study is to evaluate clinical, laboratory and radiological
      features and the outcome of patients with TA in our hospital. METHODS: The
      hospital files of patients who were followed with the diagnosis of TA between the
      years 1973 and 2003 in Hacettepe University Hospital were retrospectively
      evaluated. RESULTS: Male/female ratio was 5/40, and the mean age was 34 years (18
      59). Constitutional symptoms were present in 71% of the patients. Claudication
      and pallor of the extremity, decreased extremity pulsations, arterial
      hypertension, and arterial bruits were present in 44%, 56%, 58%, and 27% of the
      patients, respectively. Aortic valvular insufficiency, abdominal aortic aneurism,
      and cardiomegaly were present in four, one, and four patients, respectively. The
      initial complaint of six patients was cerebrovascular events. The distribution of
      the patients according to the angiographic findings was as follows, 56% Type I,
      18% Type II, 22% Type III, and 4% Type IV arteritis. The need for vascular
      surgical interventions were significantly less common in patients who were
      treated with immunosuppressives plus alternate dose steroids (6%) compared to
      patients who were treated only with antiaggregant agents (33%). CONCLUSIONS: The
      demographic and angiographic findings of our patients were similar to previous
      observations from Japan and Italy, and disclose distinct clinical features in
      comparison to other Asian countries. Alternate-day glucocorticoids plus cytotoxic
      drugs may be beneficial and safe in patients with TA.

PMID- 15262044
TI  - Ventricular hypertrophy increases NT-proBNP in subjects with and without
      hypertension.
AB  - BACKGROUND: It has been published that hypertension (HT) must be taken into
      account when using NT-proBNP, but left ventricular (LV) hypertrophy without HT
      could be a cause of NT-proBNP elevation. In a population study we compared NT
      proBNP in subjects with hypertrophy, with and without diagnosis of HT. METHODS:
      We studied 215 subjects from a random sample of 432 people who had declared to
      suffer from dyspnea. These 432 subjects were referred to their hospital where
      blood samples were taken, an echo-Doppler study was performed and a specific
      questionnaire was completed. We got a positive answer from 215, and 52 (24%) have
      LV hypertrophy. RESULTS: When we compared NT-proBNP in non-hypertrophic
      population, 148 +/- 286 pg/ml, with NT-proBNP in LV hypertrophic population, 202
      +/- 209 pg/ml, we found P < 0.001. In the hypertrophic group, when we compared NT
      proBNP (199 +/- 201 pg/ml) in normotensive subjects (LV mass index 170 +/- 70
      g/m2, Vp 50 +/- 18 cm/s, LVEF 62 +/- 8) with NT-proBNP (205 +/- 220 pg/ml) in
      subjects with diagnosis of HT (LV mass index 169 +/- 37 g/m2, Vp 55 +/- 20 cm/s,
      LVEF 64 +/- 10), we found NS. CONCLUSIONS: This population study shows that NT
      proBNP is elevated in patients with LV hypertrophy with or without HT. In LV
      hypertrophy the presence of HT does not influence the peptide levels
      significantly.

PMID- 15262045
TI  - Assessment of ventricular repolarization alterations in subjects with early
      repolarization.
AB  - BACKGROUND: Although the electrocardiographic (ECG) features of early
      repolarization (ER) have been studied extensively, no systematic quantification
      of ventricular repolarization in subjects with ER has been conducted so far.
      METHODS: The objective of the present study was to evaluate ECG and spatial
      vectorcardiographic (VCG) descriptors of ventricular repolarization in ER
      subjects and to associate them with the respective indices of ventricular
      depolarization. A digital 12-lead surface ECG was obtained from 108 young,
      healthy men with ER and 108 age-matched healthy controls. The maximum Q-onset-T
      end interval (QT maximum), the maximum Q-onset-T-peak interval (QTp maximum), the
      respective QT dispersion values (QT maximum-QT minimum), the rate-corrected QTC
      maximum and QTpC maximum, the QRS duration, and the VCG markers spatial T
      amplitude, spatial QRS amplitude and spatial QRS-T angle, were evaluated in ER
      subjects and controls. RESULTS: QT maximum (P = 0.05) and QTp maximum (P = 0.003)
      were higher in ER subjects than in controls, while QTC maximum (P < 0.0001) and
      QTpC maximum (P = 0.002) were lower in ER subjects than in controls. The QRS
      duration (P = 0.013), as well as the spatial T amplitude, the spatial QRS
      amplitude, and the spatial QRS-T angle were higher in ER subjects than in
      controls (P < 0.0001). The spatial T amplitude was not associated with the
      indices of ventricular depolarization neither in ER subjects, nor in controls.
      CONCLUSIONS: Ventricular repolarization, as well as depolarization, is altered in
      young, healthy males with ER compared to age-matched healthy controls.
      Ventricular depolarization and repolarization indices in ER subjects are not
      associated to each other.

PMID- 15262046
TI  - Transesophageal echocardiography for the diagnosis of coronary arteriovenous
      fistula.

PMID- 15262047
TI  - Differential electrocardiographic artifact from implanted thalamic stimulator.
AB  - Electrocardiographic (ECG) artifacts may interfere in ECG interpretation. Body
      movement, tremors, poor skin-electrode contact, recorder malfunction,
      electromagnetic interference and implantable electronic devices are the main
      reasons for ECG artifacts. Transcutaneous nerve and implanted spinal cord
      stimulators have been reported to result in ECG artifacts. With availability of
      newer implantable electronic devices, different ECG artifact patterns are being
      seen. Tremor control device is a newer implanted device used for suppression of
      tremors in patients with essential tremors or Parkinsonian tremors not adequately
      controlled by medications and where the tremor causes a significant functional
      incapacity. A differential pattern of ECG artifacts due to use of an implanted
      tremor control device is reported.

PMID- 15262048
TI  - Combination of traumatic pseudoaneurysm of descending thoracic aorta and bicuspid
      aortic valve endocarditis in a young adult.
AB  - We report on a 26-year-old man who injured in an automobile accident and
      developed post-traumatic bicuspid aortic valve endocarditis associated with
      severe regurgitation. In addition, transesophageal echocardiography (TEE)
      revealed a pseudoaneurysm of the descending thoracic aorta. The combination of
      medical and surgical therapy led to a favorable outcome.

PMID- 15262049
TI  - Atrial fibrillation and prominent J (Osborn) waves in critical hypothermia.
AB  - The J wave is a deflection that appears on the surface ECG as a late delta wave
      following the QRS complex. Also known as an Osborn wave, the J wave has been
      observed in various conditions and diseases. Our case highlights the typical
      electrocardiographic manifestations of hypothermia including the J deflection and
      ST segment elevation during atrial fibrillation. Thorough knowledge of these
      findings is important for prompt diagnosis and treatment of hypothermic states.

PMID- 15262050
TI  - Hybrid treatment strategy for papillary muscle rupture in acute myocardial
      infarction.

PMID- 15262051
TI  - Giant unruptured aneurysm of right valsalva sinus detected by magnetic resonance
      imaging.
AB  - This report describes a 58 -year -old patient with a giant unruptured
      asymptomatic aneurysm of right valsava sinus, as well as the significant
      contribution of magnetic resonance imaging in diagnosis of this cardiovascular
      disorder and identification of its relationship with surrounding thoracic organs.

PMID- 15262052
TI  - Acute blindness as the presenting symptom of ST segment elevation myocardial
      infarction.
AB  - This case report shows acute blindness as the first symptom of a silent anterior
      wall myocardial infarction. Although uncommon, all patients with a ST segment
      elevation myocardial infarction and a simultaneous neurological defect need
      additional assessment.

PMID- 15262053
TI  - Microwave-assisted immunostaining: a new approach yields fast and consistent
      results.
AB  - Advances in microwave technology permitted the development of new antigen
      labeling techniques. The recent microwave development of a true variable wattage
      unit designed for laboratory use and an apparatus for dampening standing wave
      radiation patterns have allowed investigators to better control the conditions
      within a microwave cavity. Thus, operating limits thought to be endemic to
      microwave-assisted protocols could be effectively mitigated. Standard protocols
      for histochemistry call for prolonged incubations and numerous rinses that add
      considerable time to the procedure. Here, we present microwave-assisted staining
      protocols for floating rat brain sections and cultured rat hippocampal cells.
      Acetylcholinesterase (ACHE) histochemistry and immunocytochemistry were conducted
      inside a specially designed and configured laboratory microwave oven. As a
      control additional tissue sections were stained on the bench and treated in the
      same manner as those in the microwave. Labeling was minimal in the control
      tissue, but specific, high contrast staining was present in the microwave group.
      Tissues were evenly stained with minimal background, and anatomical structures
      were easily detected. Also, the differences between lesioned and intact sides of
      the brain were obvious and agreed with previous observations. Microwave-assisted
      methods resulted in significantly shorter protocol times (approximately 10-fold)
      resulting in staining patterns of equal or superior quality to those obtained
      using conventional methods.

PMID- 15262054
TI  - Over-pulsing degrades activated iridium oxide films used for intracortical neural
      stimulation.
AB  - Microelectrodes using activated iridium oxide (AIROF) charge-injection coatings
      have been pulsed in cat cortex at levels from near-threshold for neural
      excitation to the reported in vitro electrochemical charge-injection limits of
      AIROF. The microelectrodes were subjected to continuous biphasic current pulsing,
      using an 0.4V (versus Ag|AgCl) anodic bias with equal cathodal and anodal pulse
      widths, for periods up to 7h at a frequency of either 50Hz or 100Hz. At charge
      densities of 3mC/cm(2), histology revealed iridium-containing deposits in tissue
      adjacent to the charge-injection sites and scanning electron microscopy of
      explanted electrodes revealed a thickened and poorly adherent AIROF coating.
      Microelectrodes pulsed at 2mC/cm(2) or less remained intact, with no histologic
      evidence of non-biologic deposits in the tissue. AIROF microelectrodes challenged
      in vitro under the same pulsing conditions responded similarly, with electrodes
      pulsed at 3mC/cm(2) showing evidence of AIROF delamination after only 100s of
      pulsing at 100Hz (10,000 pulses total), while electrodes pulsed at 2mC/cm(2) for
      7h at 50Hz (1.3 x 10(6) pulses total) showed no evidence of damage. In vitro
      electrochemical potential transient measurements in buffered physiologic saline
      indicate that polarizing the AIROF beyond the potential window for electrolysis
      of water (-0.6 to 0.8V versus Ag|AgCl) results in the observed degradation.

PMID- 15262055
TI  - A novel rodent neck pain model of facet-mediated behavioral hypersensitivity:
      implications for persistent pain and whiplash injury.
AB  - Clinical, epidemiological, and biomechanical studies suggest involvement of
      cervical facet joint injuries in neck pain. While bony motions can cause
      injurious tensile facet joint loading, it remains speculative whether such
      injuries initiate pain. There is currently a paucity of data explicitly
      investigating the relationship between facet mechanics and pain physiology. A
      rodent model of tensile facet joint injury has been developed using a customized
      loading device to apply two separate tensile deformations (low, high; n = 5 each)
      across the C6/C7 joint, or sham (n = 6) with device attachment only. Microforceps
      were rigidly coupled to the vertebrae for distraction and joint motions tracked
      in vivo. Forepaw mechanical allodynia was measured postoperatively for 7 days as
      an indicator of behavioral sensitivity. Joint strains for high (33.6 +/- 3.1%)
      were significantly elevated (P < 0.005) over low (11.1 +/- 2.3%). Digitization
      errors (0.17 +/- 0.20%) in locating bony markers were small compared to measured
      strains. Allodynia was significantly elevated for high over low and sham for all
      postoperative days. However, allodynia for low injury was not different than
      sham. A greater than three-fold increase in total allodynia resulted for high
      compared to low, corresponding to the three-fold difference in injury strain.
      Findings demonstrate tensile facet joint loading produces behavioral sensitivity
      that varies in magnitude according to injury severity. These results suggest that
      a facet joint tensile strain threshold may exist above which pain symptoms
      result. Continued investigation into the relationship between injury mechanics
      and nociceptive physiology will strengthen insight into painful facet injury
      mechanisms.

PMID- 15262056
TI  - Characterization of dopamine transport in crude synaptosomes prepared from rat
      medial prefrontal cortex.
AB  - Accumulating evidence suggests that dopamine (DA) uptake into mesocortical
      neurons may be regulated through mechanisms that are markedly different from
      those observed in nigrostriatal or mesoaccumbens systems. The current studies
      were conducted to develop a rapid and sensitive DA uptake assay in crude
      synaptosomes prepared from the medial prefrontal cortex (mPFC) of a single
      animal. Uptake of DA into the mPFC was saturable, linear with respect to protein
      concentration, time dependent, and sensitive to the effects of monoamine
      transport inhibitors. Saturation analysis revealed the K(m) and V(max) values for
      DA transport in the mPFC were approximately 60 nM and 6.5 pmol/min mg protein,
      respectively. A significant amount of DA uptake in the mPFC was more sensitive to
      inhibition by nisoxetine compared to GBR12909, fluoxetine (FLX), and cocaine
      (COC), suggesting the norepinephrine transporter (NET) plays an important role in
      the clearance of DA within this region. The described assay conditions would be
      useful in examining DA uptake within specific brain regions obtained from a
      single animal.

PMID- 15262057
TI  - The solubilizing detergents, Tween 80 and Triton X-100 non-competitively inhibit
      alpha 7-nicotinic acetylcholine receptor function in Xenopus oocytes.
AB  - Because many studies rely upon detergents to solubilize lipophilic agents such as
      cannabinoid drugs, we examined the effect of commonly employed detergents on the
      function of the cloned alpha(7) subunit of the nicotinic ACh receptor. Homomeric
      alpha(7) receptors were expressed in Xenopus oocytes and the two-microelectrode
      voltage-clamp technique was used to assess their electrophysiological properties.
      The detergents Tween 80 and Triton X-100 reversibly inhibited ACh (100 microM)
      induced inward currents in a concentration-dependent manner, with IC(50) values
      of 610 nM and 1.4 microM, respectively. The effects of these detergents were
      independent of membrane potential, and they were not mediated by endogenous
      Ca(2+)-dependent Cl(-) channels, since they were unaffected by intracellularly
      injected BAPTA, and recorded in Ca(2+)-free bathing solution containing 2 mM
      Ba(2+). Both detergents also decreased the maximal effect of ACh, without
      significantly affecting its EC(50), indicating a non-competitive interaction with
      the nACh alpha(7) receptors. In contrast to the effects of these detergents, we
      found that cholic acid (10 microM), DMSO (10 microM) and Tocrisol (0.01% v/v) did
      not cause a significant effect on nicotinic responses. In conclusion, we
      demonstrate that the detergents Tween 80 and Triton X-100 are potent inhibitors
      of neuronal nACh alpha(7) receptors expressed in Xenopus oocytes, and we suggest
      that studies utilizing these detergents to solubilize lipophilic drugs should be
      scrutinized for such effects.

PMID- 15262058
TI  - A molecular technique for detecting the liberation of intracellular zinc in
      cultured neurons.
AB  - We have previously reported that oxidative stimuli liberate Zn(2+) from
      metalloproteins, a phenomenon that can trigger neuronal cell death. Excessive
      intracellular Zn(2+) in many cell types triggers the expression of genes that
      encode metal binding proteins, such as metallothionein, via the activation and
      nuclear translocation of metal response element (MRE)-binding transcription
      factor-1 (MTF-1). Cd(2+) strongly induces nuclear translocation of MTF-1 in non
      neuronal cells, but it does so by displacing Zn(2+) from its metal binding sites
      within the cell and increasing the intracellular concentration of this ion. Here,
      we describe the use of MRE-driven expression of a luciferase reporter gene as a
      sensitive molecular assay for detecting increases in intracellular zinc
      concentrations. MRE transactivation was induced in primary cortical neurons upon
      brief exposure to Zn(2+) or Cd(2+). Enhanced MRE transactivation was observed
      upon co-exposure of neurons to Cd(2+) together with NMDA, as this metal can
      permeate through the receptor channel. Luciferase expression was observed
      regardless of whether or not neurons had been co-transfected with an MTF-1
      containing plasmid, suggesting the presence of an endogenous MTF-1-like protein.
      Indeed, RT-PCR revealed that MTF-1 mRNA is present in neurons. In contrast, MTF-1
      deficient dko7 cells were only observed to have MRE transactivation when co
      transfected with MTF-1. Our results indicate that Cd(2+) can effectively induce
      transactivation of MRE in neurons by liberating Zn(2+) from its intracellular
      binding sites.

PMID- 15262059
TI  - An automated assay of the behavioral effects of cocaine injections in adult
      Drosophila.
AB  - Introducing Drosophila models in neuropharmacological research helps to discover
      new mechanisms of drug action. In fruit flies, the pharmacobehavioral approach
      has been used to evaluate the effects of drugs of abuse including cocaine.
      Standard procedures of cocaine administration to flies employ drug vaporization
      whereas behavior is evaluated either by trained observers or by videotaping
      followed by analysis via a computer-operated tracking system. Because in
      mammalian studies cocaine is typically administered by injection, a procedure
      that ensures precise and timely dose delivery, we developed a method for
      injecting cocaine into adult Drosophila. To objectively measure the behavioral
      response of flies to cocaine injections, we adapted the standard Drosophila
      Activity Monitoring System (Trikinetics). We found that in wild-type Canton S
      flies, cocaine injections produce a dose-dependent increase in the number of
      hyperactivity bursts and that repeated injections of cocaine produce behavioral
      sensitization. Acute responses to cocaine were observed also in period null
      (per(0)) mutant flies, but in these flies, repeated injections of cocaine did not
      produce sensitization. In conclusion, we developed a method for accurately
      measuring the behavioral effects of cocaine in adult fruit flies that can be
      applied to studies of the mechanisms of behavioral sensitization.

PMID- 15262060
TI  - Evoking defined gaze directions in untrained awake monkeys.
AB  - Monkeys were partially surrounded by opaque screens except for some distant small
      holes through which they observed various stimuli or actions, or well-defined
      background patterns. Gaze direction was measured by an infrared cornea reflection
      method. Without training or reward, the animal's gaze was directed through one of
      the holes for 10-30% of the total time. With holes of appropriately small
      diameter, the gaze direction can be defined within a range of about 1 degree.
      Durations of individual glances through the holes, and dependencies on the nature
      of the displays are reported. The procedure is suited for the
      electrophysiological investigation of natural, especially foveal vision.

PMID- 15262061
TI  - Online prediction of self-paced hand-movements from subthalamic activity using
      neural networks in Parkinson's disease.
AB  - The significance of local field potential (LFP) activity in the subthalamic
      nucleus (STN) of patients with Parkinson's disease is unclear. Here we show that
      it is possible to predict self-paced hand-movements from the oscillatory nature
      of the STN LFP on a trial-by-trial basis. To this end we used a neural networks'
      classification algorithm on features representing different measures of spectral
      activity. Our experiments were simulated to process online LFP signal recordings
      collected beforehand from macroelectrodes implanted in STN. With spectral
      features extracted via wavelet transformation, we were able to predict a
      voluntary hand-movement's onset with 95% sensitivity and 77% specificity. Most
      predictions were made over a second in advance of the movement. We conclude that
      oscillatory LFP activity in STN is directly or indirectly related to processes
      involved in motor preparation. The ability to predict movement in real-time may
      open up several experimental and therapeutic possibilities.

PMID- 15262062
TI  - Quantitative assessment of the effect of CNQX on paired-pulse facilitation in the
      anterior cingulate cortex.
AB  - Paired-pulse facilitation (PPF) is a form of short-term plasticity which has been
      used qualitatively to characterize the action of neuroactive compounds. The aims
      of the present study were to develop a model that allows the quantitative
      assessment of PPF and to evaluate the influence of CNQX, an AMPA receptor
      antagonist, on synaptic plasticity based on parameters derived from this model.
      Experiments were performed on brain slices taken from the coronal anterior
      cingulate cortex (ACC) of Sprague-Dawley rats. Stimulation was applied to layer 5
      of the ACC. In all experiments, the stimuli comprised a pair of biphasic pulses
      generated by an isolated pulse stimulator under software control. An inter-pulse
      interval of 40 ms was employed, and the evoked extracellular field potentials in
      layer 2/3 of the ACC were recorded. An equation was adopted to describe the PPF
      at different stimulation intensities. Nonlinear fitting was used to obtain the
      coefficients of the equation which would allow the description of the
      experimental data. CNQX exerted an influence on the area under the curve for the
      PPF versus stimulation plot by changing the values of the parameter K (the
      voltage causing a half-maximal response). The model was elaborated based on
      features of the ligand-receptor interaction which can be reliably specified
      empirically, and its applicability was illustrated by characterizing the
      influence of CNQX on PPF in the ACC. An algorithm for the assessment of PPF using
      different sets of parameters is also discussed.

PMID- 15262063
TI  - Serial induction of mutations by ethylnitrosourea in PC12 cells: a new model for
      a phenotypical characterization of the neurotoxic response to 6-hydroxydopamine.
AB  - Here we show that the serial generation of allelic mutations by treatment with
      the mutagen ethylnitrosourea (ENU) in PC12 cells provides a new model for the
      phenotypical dissection of biological properties. We tested this approach in the
      neurotoxic 6-OHDA model of Parkinson's disease in PC12 cells which has been
      widely used as an in vitro model for the investigation of the molecular
      pathogenesis of neuronal cell death and for novel treatment approaches. ENU
      treatment at doses of 0.2 and 0.3 mg/ml for 1 h resulted in 35 and 25% surviving
      PC12 cells, respectively, which showed mutation frequencies of approximately 10
      mutations per genome. Clones derived from single ENU treated PC12 cells showed
      marked differences in their resistance against 6-OHDA. The phenotypical analysis
      of resistant and sensitive clones showed a differential transcriptional
      regulation of multiple genes. The applicability of this approach could be
      demonstrated by the identification of the rat TM9SF1 gene coding for a
      transmembrane protein of the nonaspanin superfamily as a regulated gene in PC12
      clones resistant against 6-OHDA. Our data demonstrate the suitability of this
      model for the investigation of the molecular pathogenesis of neurodegeneration
      and for high-throughput analysis, e.g. for drug discovery.

PMID- 15262064
TI  - High-performance liquid chromatography/tandem mass spectrometry assay for the
      determination of 1-methyl-4-phenyl pyridinium (MPP+) in brain tissue homogenates.
AB  - A high-throughput liquid chromatography/tandem mass spectrometry method has been
      developed for the quantitative assessment of 1-methyl-4-phenylpyridinium (MPP+)
      in brain tissue samples. This separation is based on reversed phase
      chromatography using formic acid and acetonitrile as the mobile phase. Using
      gradient separation conditions, MPP+ was resolved within 5 min and detected using
      tandem mass spectrometry in the positive ion electrospray mode. The limit of
      detection for MPP+ was found to be 1 fmol on column with a signal to noise ratio
      of 3:1. The assay has been used routinely in our laboratory for the measurement
      of MPP+ levels in brain tissue from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-treated mice, and can be used to distinguish neuroprotective efficacy and
      monoamine oxidase inhibition.

PMID- 15262065
TI  - Detection of chronic sensorimotor impairments in the ladder rung walking task in
      rats with endothelin-1-induced mild focal ischemia.
AB  - A comprehensive evaluation of the effects of neuroprotection, neurogenesis, and
      compensatory mechanisms on the outcome of ischemic insults requires assessment of
      morphological and functional parameters. Behavioural tests are essential when
      recording performance throughout the time course of an experiment and the results
      bear predictive value in preclinical animal models. The goal of this study was to
      establish a behavioural test procedure for a model of transient focal ischemia
      induced by injection of endothelin-1 (eMCAO) that results in relatively mild
      behavioural deficits. The test protocol used in the present study allows
      evaluation of quantitative and qualitative impairments in skilled motor
      performance and is sensitive to detect chronic deficits at chronic post-ischemic
      time intervals. The ladder rung walking task [J. Neurosci. Methods 115 (2002)
      169] is a motor test that assesses skilled walking and measures both forelimb and
      hindlimb placing, stepping and inter-limb co-ordination. In this study we tested
      the effect of two different technical variants of endothelin-1 application on
      infarct volume and motor skills (1) application via pre-implanted guiding cannula
      in awake animals and (2) via direct injection under halothane anaesthesia. We
      showed that the ladder rung walking task is sensitive in the assessment of loss
      of fine motor function after induction of relatively small lesions. In animals
      with implanted cannulas we found a smaller infarct area and an increase in
      placement errors prior to ischemia animals with eMCAO under anaesthesia showed a
      long lasting impairment of the contralateral forelimb up to 4 weeks post-eMCAO.

PMID- 15262066
TI  - Transmembrane dye labeling and immunohistochemical staining of
      electrophysiologically characterized single neurons.
AB  - Numerous studies have used whole-cell patch recording to characterize the
      electrophysiology of neurons and, via intracellular dye filling, the detailed
      morphology of the same cells. However, it has been difficult to demonstrate the
      presence of small soluble molecules within such cells, because washout of the
      soluble contents of the cell into the patch pipette precludes their later
      detection by immunohistochemistry. This leaves a major gap in our understanding
      of circuits made up of neurochemically heterogeneous neurons. To bridge this gap
      we have developed a transmembrane labeling approach, employing membrane-permeant
      dye in conjunction with perforated patch electrophysiology. Using this method we
      have successfully recorded from juxtaglomerular cells in the olfactory bulb,
      reconstructed the morphology of the cells, and demonstrated expression of soluble
      neurochemical markers within the same cells. This new technique provides a
      reliable means to link the physiology, morphology, and neurochemistry of single
      identified neurons studied using patch-clamp recording.

PMID- 15262067
TI  - Subcellular analysis of aberrant protein structure in age-related
      neurodegenerative disorders.
AB  - Subcellular interactions of neurodegenerative disease proteins may provide a
      basic molecular mechanism underlying neuronal disorders. Each protein may also
      exhibit activities related to normal cell structure and function. It may be
      necessary to develop methodologies to distinguish between normal and abnormal
      intracellular interactions of such proteins in human cells. The latter would
      result in distinct perturbations in cell function depending both on the specific
      protein or nucleic acid interactions as well as its subcellular localization.
      Individual neurodegenerative disorders may be characterized by distinct
      alterations in subcellular neuronal protein structure and function. We developed
      as a basic experimental paradigm a novel human cell system to identify and
      examine such abnormal neuronal protein structures. The basic rationale is that
      neurodegenerative protein interactions would result in the formation of
      intracellular high molecular weight (HMW) complexes in cells from afflicted
      individuals. Following cell fractionation these unique structures could be
      detected by gradient sedimentation coupled with immunoblot analysis. They would
      not be observed in age matched control normal human cells. We now report that
      this procedure has been successfully used to determine a unique subcellular
      alteration of beta-amyloid precursor protein (beta-APP) structure in Alzheimer's
      disease (AD) cells. The latter was not observed in normal cells. Similar
      structural alterations were observed for glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), a protein known to bind to beta-APP in vitro. The utility of this model
      system to interrelate aberrant protein interactions of neurodegenerative disease
      proteins and their subcellular localization is considered.

PMID- 15262068
TI  - Kinetic characterization of novel NR2B antagonists using fluorescence detection
      of calcium flux.
AB  - To facilitate the discovery of novel N-methyl-d-aspartate (NMDA) receptor
      antagonists, we have developed a high-throughput functional assay based on
      fluorescence detection of free intracellular calcium concentrations. Mouse
      fibroblast L(tk-) cells expressing human NR1a/NR2B NMDA receptors were plated in
      96-well plates and loaded with fluorescence calcium indicator fluo-3 AM. NR2B
      antagonists were added after stimulation of NMDA receptors with 10 microM
      glutamate and 10 microM glycine. Changes in fluorescence after the addition of
      the antagonists were fitted by a single exponential equation providing k(obs).
      The concentration dependence of k(obs) was linear for all NR2B antagonists at
      concentrations where k(obs) < 0.2 s(-1). The values of k(obs) for six
      structurally distinct NR2B antagonists were in the range of 1.1 to 7.5 x 10(5) M(
      1)s(-1). These values were several orders of magnitude slower than that obtained
      for diffusion limited Mg(2+) channel block. The rate constants k(off) provided
      the values of t(1/2) for dissociation of NR2B antagonists in the range of 1.8 min
      for ifenprodil to 240 min for the slowest novel antagonist. The IC(50) values
      obtained from the end-point fluorescence measurements agree with K(d) values
      calculated from kinetic measurements. All kinetic constants, obtained using our
      fluorescence method, correlate well with data measured by voltage clamp.

PMID- 15262069
TI  - An ex vivo method for evaluating the biocompatibility of neural electrodes in rat
      brain slice cultures.
AB  - Failure of neural recording electrodes implanted in the brain is often attributed
      to the formation of glial scars around the implant. A leading cause of scar
      formation is the electrode material. Described below is an approach to evaluate
      the biocompatibility of novel electrode materials in a representative three
      dimensional model. The model, brain slice culture, accounts for the response of
      the neural tissue in the absence of the systemic response. While limitations of
      any in vitro model exist, brain slice culture provides an indication of the
      response of neurons and glia in an environment more indicative of the in vivo
      environment than two-dimensional cell culture of glia or neurons alone.
      Polybenzylcyclobutene (BCB) electrodes were developed as test materials for
      flexible electrodes due to ease of processing, low water uptake, and inherent
      flexibility when formed in thin sheets. Biocompatibilty of the BCB neural
      electrodes was evaluated using living brain slices derived from the hippocampal
      regions of 100 g CD rats. Importantly, fewer animals can be used in brain slice
      culture to evaluate the neural tissue response than when using live animals,
      since several slices can be obtained per animal. Cellular response to the
      electrodes was evaluated at 0, 7, and 14 days. At all time points living cells,
      both neurons and glia, were observed in the vicinity of the electrode. In
      addition, cells were observed migrating out from the brain slices onto the shank
      of the BCB electrode. Brain slice culture is shown to be a viable alternative to
      in vivo evaluation, in that the response of both neurons and glia can be
      evaluated in a native three-dimensional state, while sacrificing fewer animals.
      Future in vivo evaluation with BCB will provide definitive answers on the degree
      of glial scarring in response to this new and biocompatible electrode material.

PMID- 15262070
TI  - Electrical stimulation of isolated retina with microwire glass electrodes.
AB  - The development of high-resolution retinal prostheses fabricated from silicon
      wafers presents an interesting problem: how to electrically bridge the space
      between the flat silicon wafer and the curved retinal surface. One potential
      "bridge" is a microwire glass electrode. In this paper we present our results in
      evaluating microwire glass electrodes. We stimulated isolated rabbit retina (n =
      5) with a 0.0256 cm(2) microwire electrode. The current and pulse duration were
      varied from 498 to 1660 microA and 0.1 to 3 ms, respectively. We found that short
      pulses produced more spikes per coulomb and longer pulses produced more spikes
      per milliamp. The optimal pulse duration range of 0.7-1 ms was identified as a
      compromise between the advantages of short and long pulses. Stimulation of
      isolated rabbit retina with microwire glass results in consistent neuronal spike
      formation at safe charge density, 20.7 +/- 4.3 microC/cm(2). We also examined the
      response of retinas (n = 6) to stimulation with a smaller microwire electrode,
      0.0002 cm(2). We found that less current was required (15 microA versus 756
      microA) for a 1 ms pulse, but at the expense of greater charge density (75
      microC/cm(2) versus 29.5 microC/cm(2)). Nonetheless, a 128-fold reduction in area
      resulted in only a 2.7-fold increase in charge density required for a 1 ms pulse
      duration. The results presented here indicate that microwire glass can be used as
      a neural stimulating electrode to bridge the gap between flat microelectronic
      stimulator chips and curved neuronal tissue.

PMID- 15262071
TI  - Generation of functionally competent single bovine adrenal chromaffin cells from
      cell aggregates using the neutral protease dispase.
AB  - A simple and efficient procedure has been developed to enzymatically dissociate
      aggregates of bovine adrenal chromaffin cells in suspension culture into viable,
      responsive single cells. For dissociation, the neutral protease dispase is added
      directly to the culture medium for a minimum of 3 h, followed by incubation of
      the cells in Hank's calcium-magnesium-free balanced salt solution at 37 degrees C
      with intermittent trituration to facilitate dispersion. This procedure generates
      a population of phase-bright single cells that are round in morphology, take up
      the dye neutral red, exclude the dye trypan blue and readily attach to tissue
      culture dishes coated with collagen, fibronectin or polylysine, thereby
      permitting applications that require plated-down conditions. When transferred to
      culture medium, the cells begin to reaggregate. By altering the length of time
      the cells are incubated in culture medium prior to attachment, the degree of
      reaggregation can be controlled to obtain plate-down profiles that consist of
      both isolated cells and cells in aggregates of varying sizes. Returning
      dissociated cells to suspension culture results in the reformation of large cell
      aggregates. Several measures of chromaffin cell function were indistinguishable
      for dissociated cells placed either in monolayer culture or suspension culture
      versus non-dissociated cells, implying that the dissociation procedure does not
      alter cellular responses or cause cellular damage.

PMID- 15262073
TI  - Neural spike classification using parallel selection of all algorithm parameters.
AB  - The Forster-Handwerker template-matching algorithm (J. Neurosci. Methods 31
      (1990) 109) classifies neuronal spikes according to three parameters selected by
      the experimenter prior to running the algorithm. Thousands of different
      combinations of these parameter values are possible producing hundreds of
      different classifications for each input file. Using a 40-processor Linux-based
      parallel computing cluster, we ran their algorithm with an effective sampling of
      all combinations of parameter values in order to generate a list of the
      classifications that can be generated by the algorithm. A distance measure was
      used to quantify the similarity between classifications and then to create a
      distance table containing entries for the distances between all pairs of
      classifications. Using a self-organizing neural network (SON) and the distance
      table we group the classifications by similarity and select the best
      representative classifications that the Forster-Handwerker algorithm can produce.

PMID- 15262072
TI  - A preclinical post laminectomy rat model mimics the human post laminectomy
      syndrome.
AB  - Chronic low back pain with sciatica complicating post laminectomy surgery is
      poorly understood. It is likely that some aspects of persistent pain of the
      syndrome results from spinal facilitation in which there is lowering of pain
      excitation levels. A small animal preclinical model is needed that mimics the
      clinical condition to permit detailed studies of the underlying altered
      neurochemistry of the sensory pathways. We propose herein a rat laminectomy model
      containing the elements required for study of the neurobiology of the condition.
      The model consists of a surgical laminectomy that includes L5 spinal nerve
      manipulation and disc injury, elements necessarily employed in human disc
      herniation surgery. At 8 weeks post laminectomy the proposed model demonstrates
      paraspinous muscle spasm, tail contracture, behavioral pain behavior, tactile
      allodynia, epidural and nerve root scarring, and nerve root adherence by scar to
      the underlying disc and adjacent pedicle. Two underlying pain facilitation states
      are invoked in the clinical condition: (1) an inflammatory state required to
      achieve wound healing; and (2) a nerve injury state resulting from nerve
      manipulation and subsequent epidural scarring, spinal nerve scarring, and spinal
      nerve tethering to the adjacent disc and pedicle. Both pain facilitation states
      are active in the model.

PMID- 15262074
TI  - Nitrogen disruption of synaptoneurosomes: an alternative method to isolate brain
      mitochondria.
AB  - Mitochondria are known to be localized in synaptic and non-synaptic compartments
      in the brain. Synaptoneurosomes, which contain high numbers of mitochondria, may
      act as a major contaminant of currently used isolation techniques. Currently,
      there is no method employed to successfully disrupt synaptoneurosomes and isolate
      both synaptic and non-synaptic mitochondria without structural or functional
      damage. A novel method is reported here for disruption of synaptoneurosomes and
      isolation of total brain mitochondria from synaptic and non-synaptic sources
      using a nitrogen decompression technique. Nitrogen gas was dissolved into crude
      mitochondrial preparations and maintained under constant, moderate pressure.
      After a short incubation, the pressure was released causing the nitrogen to come
      out of solution as growing bubbles, which ruptures cellular and synaptoneurosomal
      membranes. Mitochondria isolated using this rapid technique were bioenergetically
      competent and exhibited functional characteristics comparable to mitochondria
      isolated using traditional techniques. This nitrogen decompression technique will
      allow for further characterization of synaptic pools of mitochondria, which are
      almost exclusively neuronal in origin.

PMID- 15262075
TI  - Quantitative analysis of ankle hypertonia after prolonged stretch in subjects
      with stroke.
AB  - The aims of this study are to validate the hypertonia treatment/assessment system
      and to quantify the immediate effect of prolonged muscle stretch (PMS) on the
      inhibition of ankle hypertonia in stroke patients. For PMS treatment, ankle
      plantarflexors were stretched with a constant torque in 25 subjects with
      hemiplegia and ankle plantarflexors hypertonia. Using the developed hypertonia
      treatment/assessment system, the effects of the PMS treatment were quantified by
      comparing the reactive torque measurements of the ankle joint before and after
      the treatment sessions in terms of elastic (elastic-inertia) (K(ei)) and viscous
      (K(v)) components. It was shown that an application of PMS for 30 min using a
      constant stretching force, approximately 80% of the torque measured at the
      maximal passive ROM dorsiflexion position, significantly reduces both components
      of the ankle joint torque (P < 0.05). The present results suggested that the
      application of PMS with a constant torque could reduce not only the elasticity of
      the hypertonic muscles, but also their viscosity in the stroke patients.

PMID- 15262076
TI  - Improvements in the intraluminal thread technique to induce focal cerebral
      ischaemia in rabbits.
AB  - Although the intraluminal thread technique has been used to induce focal cerebral
      ischaemia in rabbits, its success rate is not high. We, therefore, attempted to
      improve the stability and reproducibility of this method by using thread tips of
      appropriate diameter as determined from the anatomical characteristics of the
      carotid and cerebral arteries of New Zealand white rabbits. Following
      intraarterial injection of casting material, we tested threads of four different
      tip diameters to determine the optimal thread tip that could occlude the middle
      cerebral artery (MCA). 2,3,5-Triphenyltertrazolium chloride (TTC) staining showed
      that, consistent with the intraluminal diameter of the MCA from the arterial
      casts ( 0.50 +/- 0.06 mm), thread with 0.51-0.55 mm tip diameter was optimal for
      the occlusion of the MCA. Ability to induce focal cerebral ischaemia was also
      dependent on variations in the anatomy of the internal carotid artery (ICA),
      especially the origin of the occipital artery. Our results suggest that use of
      appropriately sized thread and accurate manipulation of its tip significantly
      improves the stability and reproducibility of this model.

PMID- 15262077
TI  - Fourier-, Hilbert- and wavelet-based signal analysis: are they really different
      approaches?
AB  - Spectral signal analysis constitutes one of the most important and most commonly
      used analytical tools for the evaluation of neurophysiological signals. It is not
      only the spectral parameters per se (amplitude and phase) which are of interest,
      but there is also a variety of measures derived from them, including important
      coupling measures like coherence or phase synchrony. After reviewing some of
      these measures in order to underline the widespread relevance of spectral
      analysis, this report compares the three classical spectral analysis approaches:
      Fourier, Hilbert and wavelet transform. Recently, there seems to be increasing
      acceptance of the notion that Hilbert- or wavelet-based analyses be in some way
      superior to Fourier-based analyses. The present article counters such views by
      demonstrating that the three techniques are in fact formally (i.e.
      mathematically) equivalent when using the class of wavelets that is typically
      applied in spectral analyses. Moreover, spectral amplitude serves as an example
      to show that Fourier, Hilbert and wavelet analysis also yield equivalent results
      in practical applications to neuronal signals.

PMID- 15262078
TI  - It is time to stop putting children second in the UK and USA.

PMID- 15262079
TI  - A window of opportunity for Africa's health information.

PMID- 15262080
TI  - Health information for all by 2015?

PMID- 15262081
TI  - Modelling the effect of screening for cervical cancer on the population.

PMID- 15262083
TI  - Willing oneself better on placebo--effective in its own right.

PMID- 15262082
TI  - Programming obesity in childhood.

PMID- 15262084
TI  - Non-accidental injury in children: making sense of the courts.

PMID- 15262085
TI  - Genocide: burden of proof and inaction is costing lives in Sudan.

PMID- 15262086
TI  - The future of the cigarette and its market.

PMID- 15262087
TI  - Depression and anxiety in the developing world: is it time to medicalise the
      suffering?

PMID- 15262090
TI  - Pulmonary embolism.

PMID- 15262091
TI  - Pulmonary embolism.

PMID- 15262092
TI  - Pulmonary embolism.

PMID- 15262094
TI  - Pulmonary embolism.

PMID- 15262095
TI  - Pulmonary embolism.

PMID- 15262096
TI  - Rotavirus vaccines.

PMID- 15262097
TI  - Rotavirus vaccines.

PMID- 15262098
TI  - Alcohol intake, serum uric acid concentrations, and risk of gout.

PMID- 15262100
TI  - Developmental dyslexia and zinc deficiency.

PMID- 15262101
TI  - Political neglect in India's health.

PMID- 15262102
TI  - The cervical cancer epidemic that screening has prevented in the UK.
AB  - BACKGROUND: Recent reports suggest that the reduction in mortality achieved by
      the UK national cervical screening programme is too small to justify its
      financial and psychosocial costs, except perhaps in a few high-risk women.
      METHODS: We analysed trends in mortality before 1988, when the British national
      screening programme was launched, to estimate what future trends in cervical
      cancer mortality would have been without any screening. FINDINGS: Cervical cancer
      mortality in England and Wales in women younger than 35 years rose three-fold
      from 1967 to 1987. By 1988, incidence in this age-range was among the highest in
      the world despite substantial opportunistic screening. Since national screening
      was started in 1988, this rising trend has been reversed. INTERPRETATION:
      Cervical screening has prevented an epidemic that would have killed about one in
      65 of all British women born since 1950 and culminated in about 6000 deaths per
      year in this country. However, these estimates are subject to substantial
      uncertainty, particularly in relation to the effects of oral contraceptives and
      changes in sexual behaviour. 80% or more of these deaths (up to 5000 deaths per
      year) are likely to be prevented by screening, which means that about 100000 (one
      in 80) of the 8 million British women born between 1951 and 1970 will be saved
      from premature death by the cervical screening programme at a cost per life saved
      of about pound 36000. The birth cohort trends also provide strong evidence that
      the death rate throughout life is substantially lower in women who were first
      screened when they were younger.

PMID- 15262103
TI  - Association between child and adolescent television viewing and adult health: a
      longitudinal birth cohort study.
AB  - BACKGROUND: Watching television in childhood and adolescence has been linked to
      adverse health indicators including obesity, poor fitness, smoking, and raised
      cholesterol. However, there have been no longitudinal studies of childhood
      viewing and adult health. We explored these associations in a birth cohort
      followed up to age 26 years. METHODS: We assessed approximately 1000 unselected
      individuals born in Dunedin, New Zealand, in 1972-73 at regular intervals up to
      age 26 years. We used regression analysis to investigate the associations between
      earlier television viewing and body-mass index, cardiorespiratory fitness
      (maximum aerobic power assessed by a submaximal cycling test), serum cholesterol,
      smoking status, and blood pressure at age 26 years. FINDINGS: Average weeknight
      viewing between ages 5 and 15 years was associated with higher body-mass indices
      (p=0.0013), lower cardiorespiratory fitness (p=0.0003), increased cigarette
      smoking (p<0.0001), and raised serum cholesterol (p=0.0037). Childhood and
      adolescent viewing had no significant association with blood pressure. These
      associations persisted after adjustment for potential confounding factors such as
      childhood socioeconomic status, body-mass index at age 5 years, parental body
      mass index, parental smoking, and physical activity at age 15 years. In 26-year
      olds, population-attributable fractions indicate that 17% of overweight, 15% of
      raised serum cholesterol, 17% of smoking, and 15% of poor fitness can be
      attributed to watching television for more than 2 h a day during childhood and
      adolescence. INTERPRETATION: Television viewing in childhood and adolescence is
      associated with overweight, poor fitness, smoking, and raised cholesterol in
      adulthood. Excessive viewing might have long-lasting adverse effects on health.

PMID- 15262104
TI  - Effect of a treatment strategy of tight control for rheumatoid arthritis (the
      TICORA study): a single-blind randomised controlled trial.
AB  - BACKGROUND: Present treatment strategies for rheumatoid arthritis include use of
      disease-modifying antirheumatic drugs, but a minority of patients achieve a good
      response. We aimed to test the hypothesis that an improved outcome can be
      achieved by employing a strategy of intensive outpatient management of patients
      with rheumatoid arthritis--for sustained, tight control of disease activity-
      compared with routine outpatient care. METHODS: We designed a single-blind,
      randomised controlled trial in two teaching hospitals. We screened 183 patients
      for inclusion. 111 were randomly allocated either intensive management or routine
      care. Primary outcome measures were mean fall in disease activity score and
      proportion of patients with a good response (defined as a disease activity score
      <2.4 and a fall in this score from baseline by >1.2). Analysis was by intention
      to-treat. FINDINGS: One patient withdrew after randomisation and seven dropped
      out during the study. Mean fall in disease activity score was greater in the
      intensive group than in the routine group (-3.5 vs -1.9, difference 1.6 [95% CI
      1.1-2.1], p<0.0001). Compared with routine care, patients treated intensively
      were more likely to have a good response (definition, 45/55 [82%] vs 24/55 [44%],
      odds ratio 5.8 [95% CI 2.4-13.9], p<0.0001) or be in remission (disease activity
      score <1.6; 36/55 [65%] vs 9/55 [16%], 9.7 [3.9-23.9], p<0.0001). Three patients
      assigned routine care and one allocated intensive management died during the
      study; none was judged attributable to treatment. INTERPRETATION: A strategy of
      intensive outpatient management of rheumatoid arthritis substantially improves
      disease activity, radiographic disease progression, physical function, and
      quality of life at no additional cost.

PMID- 15262106
TI  - Klinefelter's syndrome.
AB  - Klinefelter's syndrome is the most common genetic cause of human male
      infertility, but many cases remain undiagnosed because of substantial variation
      in clinical presentation and insufficient professional awareness of the syndrome
      itself. Early recognition and hormonal treatment of the disorder can
      substantially improve quality of life and prevent serious consequences.
      Testosterone replacement corrects symptoms of androgen deficiency but has no
      positive effect on infertility. However, nowadays patients with Klinefelter's
      syndrome, including the non-mosaic type, need no longer be considered irrevocably
      infertile, because intracytoplasmic sperm injection offers an opportunity for
      procreation even when there are no spermatozoa in the ejaculate. In a substantial
      number of azoospermic patients, spermatozoa can be extracted from testicular
      biopsy samples, and pregnancies and livebirths have been achieved. The frequency
      of sex chromosomal hyperploidy and autosomal aneuploidies is higher in
      spermatozoa from patients with Klinefelter's syndrome than in those from normal
      men. Thus, chromosomal errors might in some cases be transmitted to the offspring
      of men with this syndrome. The genetic implications of the fertilisation
      procedures, including pretransfer or prenatal genetic assessment, must be
      explained to patients and their partners.

PMID- 15262105
TI  - Amniotic fluid S100B protein in mid-gestation and intrauterine fetal death.
AB  - Fetal death in the mid-trimester of pregnancy is unexplained and no reliable
      markers are available to identify at-risk women. We aimed to assess use of alpha
      fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case
      control study in 758 healthy women undergoing amniocentesis at mid-gestation, of
      whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746
      matched controls. Concentrations were corrected for gestational age by conversion
      to multiples of median (MoM) of healthy controls of the same gestational age.
      Concentrations of S100B, but not alpha fetoprotein, were significantly higher
      (p<0.0001) in women who later had spontaneous fetal death (median 4.431 MoM
      [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity,
      specificity, and positive and negative predictive values of S100B as a diagnostic
      test were 100%, suggesting that measurement of this protein at amniocentesis
      could be useful to identify at-risk women.

PMID- 15262107
TI  - Klinefelter's syndrome: a late diagnosis.

PMID- 15262108
TI  - Antimalarial combinations.
AB  - Multidrug resistance has rendered monotherapy for malaria useless in most parts
      of the world, and has also compromised the usefulness of many of the available
      combination chemotherapies. New antimalarial regimens are, therefore, urgently
      needed. We review the various antimalarial combinations that can be used to treat
      otherwise drug-resistant disease, and discuss what defines an ideal antimalarial
      combination regimen.

PMID- 15262109
TI  - Can we achieve health information for all by 2015?
AB  - Universal access to information for health professionals is a prerequisite for
      meeting the Millennium Development Goals and achieving Health for All. However,
      despite the promises of the information revolution, and some successful
      initiatives, there is little if any evidence that the majority of health
      professionals in the developing world are any better informed than they were 10
      years ago. Lack of access to information remains a major barrier to knowledge
      based health care in developing countries. The development of reliable, relevant,
      usable information can be represented as a system that requires cooperation among
      a wide range of professionals including health-care providers, policy makers,
      researchers, publishers, information professionals, indexers, and systematic
      reviewers. The system is not working because it is poorly understood, unmanaged,
      and under-resourced. This Public Health article proposes that WHO takes the lead
      in championing the goal of "Universal access to essential health-care information
      by 2015" or "Health Information for All". Strategies for achieving universal
      access include funding for research into barriers to use of information,
      evaluation and replication of successful initiatives, support for
      interdisciplinary networks, information cycles, and communities of practice, and
      the formation of national policies on health information.

PMID- 15262110
TI  - Determination can win the battle.

PMID- 15262111
TI  - The double duct sign.

PMID- 15262112
TI  - Extent of radical hysterectomy: evolving emphasis.
AB  - OBJECTIVE: As with other oncologic operations, the indications for and the
      technique of radical hysterectomy for cervical cancer has changed considerably
      since its initial conception in the late 19th century. This paper reviews the
      evolution of concepts concerning the extent of radical hysterectomy for cervical
      cancer. METHODS: A Medline literature search was performed through looking for
      articles published in the English language that related to radical hysterectomy
      for cervical cancer. Specific subjects that were searched included technique,
      morbidity, and histopathologic assessment of the parametria. RESULTS: Initial
      emphasis on local control and potential long-term survival gradually shifted to
      reduction of mortality and serious morbidity. Early refinements directed
      attention to the regional lymph nodes, definition of prognostic factors, and
      determination of the population of patients best suited for the operation. During
      the mid to late 20th century, a better understanding of regional and local
      prognostic factors helped clarify the role of adjuvant treatment following
      radical hysterectomy. By the mid 20th century, the mortality and serious
      morbidity rates had fallen substantially, and attention turned to reduction of
      other types of morbidity, especially urinary bladder voiding dysfunction.
      Reduction of much of the serious morbidity (urinary fistulas) and voiding
      dysfunction has been related to modifications of the extent of radical
      hysterectomy. Specific nerve-sparing techniques now have been described. However,
      maintaining full radicality continues to be emphasized at some centers.
      CONCLUSION: The current primary operative approaches to stage 1B cervical cancer
      include full radical hysterectomy, modified radical hysterectomy followed by
      adjuvant therapy in selected patients, radical hysterectomy with nerve-sparing,
      and individualization of surgical management. Studies are needed which further
      elucidate the significance of parametrial micrometastases, further define and
      refine broadly feasible nerve-sparing techniques, and more accurately
      preoperatively identify low and high risk cervical tumors. Optimally, these
      studies will remove adjuvant treatment as a confounding variable.

PMID- 15262113
TI  - Pitfalls in the sentinel lymph node procedure in vulvar cancer.
AB  - OBJECTIVES: There is an increasing interest among gynecologic oncologists to
      implement the sentinel lymph node (SLN) procedure in vulvar cancer patients in
      clinical practice. However, the safety of this promising method of staging still
      has to be proven in a randomized trial. MATERIALS AND METHODS: Two vulvar cancer
      patients are reported to illustrate pitfalls in the sentinel lymph node
      procedure. RESULTS: The phenomena of bypassing the sentinel lymph node and
      confusion about the number of removed sentinel lymph nodes are presented and
      discussed. CONCLUSION: Gynecological oncologists who perform the sentinel lymph
      node procedure in vulvar cancer patients should perform this technique by
      following a strict protocol and within the protection of a clinical trial.

PMID- 15262114
TI  - Immunohistochemical patterns for alpha- and beta-catenin, E- and N-cadherin
      expression in ovarian epithelial tumors.
AB  - OBJECTIVES: This study aims were to analyze and compare the E- and N-cadherin,
      beta- and alpha-catenin expression in benign and malignant epithelial neoplasms
      of the ovary, correlating with tumor staging, histological grade, and presence of
      metastases during evolution. METHODS: Immunohistochemical reactions were
      performed on paraffin-embedded tissues and evaluated according to the number of
      positive, stained cellular structures and reaction intensity for each molecule.
      Information about histological type and grade, tumoral stage, and disease
      evolution was obtained from the patients' clinical records. RESULTS: Most of the
      carcinomas showed more intense beta-catenin reaction (P = 0.02). More than 50% of
      the endometrioid carcinomas showed increased beta-catenin expression, with a
      large number of positive cells and more intense staining, being the same also
      observed for most of the serous benign tumors (P < 0.01). E-cadherin membrane
      expression was frequently observed in carcinomas without metastasis, whereas
      cases with metastases in evolution were negative or showing E-cadherin expression
      only in the cytoplasm (P = 0.04). N-cadherin expression differed according to
      histological type and grade and alpha-catenin was also related to histological
      type, but these findings were not conclusive. CONCLUSIONS: Increased beta-catenin
      expression was more frequent in ovarian carcinomas, especially, but not only, in
      the endometrioid ones. The maintenance of E-cadherin expression in cellular
      membrane may be an independent marker of good prognosis in ovarian cancer. New
      studies about N-cadherin and alpha-catenin and their importance during ovarian
      carcinogenesis will be required.

PMID- 15262115
TI  - Estrogens and epithelial ovarian cancer.
AB  - OBJECTIVE: Molecular mechanisms involved in ovarian carcinogenesis are still
      unclear, but there is growing evidence that estrogens promote tumor progression
      in an epithelial ovarian cancer (EOC) subgroup. METHODS: We reviewed current
      knowledge on the effects of estrogens in ovarian carcinogenesis and new potential
      research focuses concerning hormonal therapy of EOC. RESULTS: Experimentally,
      estrogen stimulates the growth of ovarian tumor cell lines expressing estrogen
      receptors (ER). We and other authors have demonstrated differential expression of
      ERalpha or beta during ovarian carcinogenesis, with overexpression of ERalpha as
      compared to ERbeta in cancer. This differential expression in ER suggests that
      estrogen-induced proteins may act as ovarian tumor-promoting agents. Among these
      proteins, c-myc, fibulin-1, cathepsin-D, or several kallikreins may play a role,
      since high expression levels have been found in EOC. Consistently, recent
      prospective epidemiological studies have indicated that estrogen replacement
      therapy in postmenopausal women may increase ovarian cancer incidence and
      mortality. CONCLUSION: Questions on the estrogen-sensitivity and potential
      benefits of new hormone therapies in an EOC subgroup should be readdressed in the
      light of recent experimental and clinical data.

PMID- 15262116
TI  - Binding of alpha2 monoclonal antibody to human cervical tumor cell (SiHa) surface
      alpha2beta1 integrin modulates MMP-2 activity.
AB  - OBJECTIVE(S): The purpose was to study the interrelationship between cell surface
      integrin receptor (alpha2beta1) and matrixmetalloproteinases. METHODS:
      Immunoprecipitation and cell adhesion assay were done to assay alpha2beta1 and
      alpha3beta1 on SiHa cell surface. Zymogram was developed to assay secreted MMP
      activity of cells grown in presence of alpha2 monoclonal antibody. Immunoblot was
      developed to assay expression of MMP-2, FAK, and p-FAK. Plasma membrane-dependent
      activation of MMP2 was performed by incubating pure MMP-2 with membrane-enriched
      fraction isolated from SiHa cells. RESULTS: Immunoprecipitation and cell adhesion
      assay results confirmed the presence of alpha2beta1 receptor on SiHa cells.
      Zymographic analysis of serum-free media collected at different time points from
      SiHa cells grown on alpha2 monoclonal antibody-coated culture dishes showed the
      expression and activation of MMP-2 within 2-4 h, confirmed by immunoblot. Western
      blot of cells grown on alpha2-coated dishes for 30 min-4 h showed increased
      phosphorylation of FAK. Membrane-enriched fraction isolated from SiHa cells was
      found to specifically activate proMMP-2 to its activated forms within 30 min.
      CONCLUSION(S): The experimental findings strongly indicate that SiHa cell surface
      alpha2beta1 regulates MMP-2 expression. Increased phosphorylation of focal
      adhesion kinase (FAK) strongly indicates the possible role of FAK in signaling
      cascade. Incubation of SiHa cell membrane fraction with pure MMP-2 strongly
      confirms the cell membrane-dependent activation of proMMP2.

PMID- 15262117
TI  - The role of HPV oncoproteins and cellular factors in maintenance of hTERT
      expression in cervical carcinoma cells.
AB  - OBJECTIVE: E6 and E7 oncoproteins of high risk type HPV modulate activities of
      host components in cell cycle regulation. Many of these factors are also involved
      in the regulation of telomerase activity or the expression of hTERT, the
      catalytic subunit. Transcription of E6 and E7 is inhibited by the papillomavirus
      E2 protein, and ectopic expression of E2 in HeLa cells has been shown to cause
      activation of the p53-growth inhibitory pathway and downregulation of the hTERT
      gene. In this study, using E2 transduction in HeLa cells, the relative importance
      of host and viral factors in the maintenance of hTERT and telomerase activity in
      cervical carcinoma cells was investigated. METHODS: Depletion of E6/E7 proteins,
      concomitant upregulation of p53, p21WAF1, and hypophosphorylated Rb, and
      downregulation of E2F1, c-Myc, and hTERT were achieved in HeLa cells through SV40
      mediated E2 transduction. And, through gene transduction, E6 and E7 proteins were
      separately re-expressed in HeLa cells that were devoid of these proteins. As
      well, E2F1, c-Myc, and p53 were ectopically expressed in HeLa cells to ascertain
      their effect on the level of hTERT expression through RT-PCR, Western blotting,
      and TRAP assays. RESULTS: Continued expression of E2F1 and c-Myc could not
      prevent hTERT downregulation caused by E2 transduction, but re-expression of
      either E6 or E7 individually reactivated hTERT expression. Finally, p53
      overexpression caused repression of the hTERT gene in the presence of E6 and E7.
      CONCLUSION: HPV E6 plays an important role in the induction and maintenance of
      high levels of hTERT in cervical carcinoma cells through direct stimulation of
      hTERT promoter and prevention of the inhibitory effects of p53. E7, but not E2F1,
      may contribute to high telomerase activity in cancer cells.

PMID- 15262118
TI  - Characterizing T-cell response in low-grade and high-grade vulval intraepithelial
      neoplasia, study of CD3, CD4 and CD8 expressions.
AB  - OBJECTIVE: The objective of our study was to compare immunocyte infiltrates in
      vulval epithelium from low-grade and high-grade vulval intraepithelial neoplasia
      (VIN) lesions to determine if difference in T-cell presence reflected the grade
      of VIN. MATERIAL AND METHODS: Thirty-six vulval specimens were obtained from 24
      patients who had previously undergone vulval biopsies for VIN, 14 high-grade
      diseases (VIN 3 with or without HPV) and 14 low-grade diseases (VIN 1 and VIN 2
      with or without HPV). Eight samples of normal vulval tissue were selected from
      the excision margins of resected vulval biopsies. The lymphocyte surface markers
      included CD3 (Pan T-cell marker), CD4 (T helper cells), and CD8 (T cytotoxic
      cells). Each tissue section was visualized under high power magnification and
      cells were counted in 10 random areas at the dermo-epidermal junction. RESULTS: A
      significantly higher number of total mean T lymphocytes were detected in VIN
      specimens compared to normal vulval tissue (P = 0.002). In low-grade VIN, there
      were significantly more CD8 cells than CD4 when compared to high-grade VIN. This
      difference in CD4/CD8 ratio was significant (P = 0.001). CONCLUSIONS: This study
      suggests that increased CD8 response in VIN is a feature of low-grade disease and
      we speculate that this may be a protective mechanism. In high-grade disease, both
      CD4 cells and CD8 cells are equally present with preservation of normal CD4/CD8
      ratio.

PMID- 15262119
TI  - Modulation of CD3-zeta as a marker of clinical response to IL-2 therapy in
      ovarian cancer patients.
AB  - OBJECTIVE: In women with advanced ovarian cancer, levels of CD3-zeta on
      peripheral blood lymphocytes have previously been demonstrated to correlate with
      responsiveness to interleukin (IL)-2 therapy. The aims of this study were to
      identify the circulating component that modulated zeta expression and to define
      whether this suppressive activity could serve as a marker of biotherapy
      responsiveness. METHODS: Sera were obtained from 17 patients with advanced
      ovarian cancer treated with intraperitoneal IL-2 in a phase I trial between 1987
      and 1990. Nine of these patients exhibited a clinical response, while eight did
      not respond. Six additional sera from age-matched, noncancer-bearing women were
      used as controls. Jurkat E6-1 cells were used to assay modulation of CD3-zeta by
      sera and serum-derived components. Jurkat cells were exposed to serum or
      chromatographically fractionated serum components for 4 days and zeta expression
      was analyzed by Western immunoblots and quantitated by densitometry. RESULTS: The
      effect of sera on zeta expression was compared between responders and
      nonresponders. Incubation of Jurkat cells with sera from responders suppressed
      CD3-zeta expression by 36.7% (vs. control treated), while treatment with sera
      from nonresponders produced an 83.7% reduction in zeta expression (difference
      between groups, P < 0.001). When sera from nonresponders were chromatographically
      fractionated, a <20 kDa component was identified that correlated with decreased
      zeta chain expression. This component was diminished in the sera of responders
      and absence in controls. CONCLUSIONS: Thus, in patients with advanced ovarian
      cancer, a circulating component, which decreases zeta expression, can be
      identified as a marker for responsiveness to IL-2 therapy.

PMID- 15262120
TI  - Radical hysterectomy followed by tailored postoperative therapy in the treatment
      of stage IB2 cervical cancer: feasibility and indications for adjuvant therapy.
AB  - OBJECTIVE: To determine the outcome, complications and likelihood of requiring
      adjuvant therapy of patients with stage IB2 cervical cancer treated with primary
      radical hysterectomy and lymph node dissection. METHODS: Clinical and pathologic
      data between 1985 and 1999 were reviewed. Associations between clinical and
      pathologic variables were tested using the Fisher's exact test. Survival was
      estimated using the Kaplan-Meier method with significance being calculated using
      the Log Rank test. RESULTS: Six hundred radical hysterectomies were performed
      during the study period. Fifty-eight of these women (9.6% of all radical
      hysterectomies) were diagnosed with FIGO stage IB2 cancers. Sixteen patients
      (28%) had positive pelvic lymph nodes. Forty-six patients (79%) had invasion
      involving the outer 1/3 of the cervical stroma, six had positive vaginal margins
      while five had occult parametrial extension. After retrospective review of the
      histopathologic data from this case series, criteria from two recently published
      prospective multicenter Gynecologic Oncology Group (GOG) trials were applied to
      this data set. According to criteria established by GOG protocol 92, 30 (52%)
      patients should have theoretically received adjuvant pelvic radiation while 21
      (36%) would have qualified for adjuvant chemotherapy and radiation according to
      the results of GOG protocol 109. In actual fact, only 35 patients (60%) received
      adjuvant radiotherapy and one received adjuvant chemo-radiation. Severe toxicity
      was unusual with two developing urinary fistulae and one having a pulmonary
      embolism. Despite the lack of adjuvant therapy in most cases, only 21 women (38%)
      recurred of whom 11 failed on the pelvic wall, with an estimated 5-year survival
      of 62.1%. CONCLUSIONS: Radical hysterectomy and tailored adjuvant radiation
      therapy in stage IB2 cervical cancer is feasible. Even without the liberal use of
      adjuvant therapy, survival in this high-risk group compares favorably to primary
      chemotherapy and radiation. According to recently published randomized clinical
      trials, most patients should receive adjuvant postoperative therapy. The benefits
      of this multimodality approach require randomized study.

PMID- 15262121
TI  - The role of topotecan for extending the platinum-free interval in recurrent
      ovarian cancer: an in vitro model.
AB  - OBJECTIVE: Topotecan, a novel topoisomerase-I inhibitor, is an active agent of
      second-line chemotherapy for extending the platinum-free interval (PFI) and
      improving the chances of a response to platinum in recurrent ovarian cancer
      patients. The aim of this study was to understand the molecular mechanism of
      topotecan-based second-line chemotherapy through an in vitro cell culture model
      and to gain clinical insight into sequencing issues for second-line treatment
      with novel agents versus retreatment with platinum. STUDY DESIGN: The human
      ovarian cancer cell line A2780 and the cisplatin resistance cell line A2780-CR
      were separately seeded in 6-well cell culture plates and then exposed to multiple
      concentrations of cisplatin plus paclitaxel or topotecan for 7 days. Surviving
      cells were recovered and cultured in drug-free media for 3 weeks and then
      replated in a 96-well microtiter plate. The LD(50) for these cells was determined
      by a cytotoxic MTT assay after exposure to multiple clinically relevant
      concentrations of cisplatin or topotecan. Surviving cells were cultured in drug
      free media for an additional 4 weeks at which time the LD(50) was reassessed for
      each cell population by a second MTT assay. Using RT-PCR and Northern blot
      hybridization to measure mRNA expression, the molecular profile of these cells in
      terms of resistance was evaluated for the multidrug-resistant gene (MDR-1),
      multidrug-resistant protein (MRP), Topoisomerase-I, and beta-Actin. RESULTS: The
      LD(50) to cisplatin was unchanged in A2780-CR cells treated by topotecan. Those
      A2780-CR cells originally exposed to higher concentrations of cisplatin became
      more resistant to cisplatin in the MTT assays, while those A2780-CR cell lines
      treated with a combination of lower cisplatin concentrations and paclitaxel
      became more sensitive to cisplatin in the MTT assay (P < 0.01). The second MTT
      assay demonstrated that the LD(50) for cisplatin in every cell line decreased
      significantly after a 4-week drug-free interval (P < 0.01). There was no
      difference in the mRNA expression for MRP or topoisomerase-I regardless of cell
      line, or type or concentration of chemotherapeutic exposure. The mRNA for MDR-1
      was uniquely overexpressed in the cisplatin-resistant cell line A2780-CR9
      initially treated with low doses of cisplatin and paclitaxel, but was not
      amplified in A2780 (P < 0.01). CONCLUSIONS: The acquired resistance to cisplatin
      in A2780 is potentially due to P-glycoprotein-mediated multidrug resistance. This
      acquired resistance to cisplatin is an unstable phenotype in that some cell
      populations become sensitive after a drug-free interval and topotecan treatment.
      This reversal of resistance, however, does not appear to be simply due to loss of
      MDR-1 expression. While in vivo confirmation is required, agents with novel
      mechanisms of action offer a strategy to extend the platinum-free interval and
      thereby improve survival in patients with recurrent ovarian cancer.

PMID- 15262122
TI  - The relationship between serum vascular endothelial growth factor, persistent
      disease, and survival at second-look laparotomy in ovarian cancer.
AB  - OBJECTIVE: To assess if the angiogenic factors vascular endothelial growth factor
      (VEGF) and D-dimer are predictive of persistent disease, early relapse, and
      survival in patients with ovarian cancer who achieve a complete clinical
      remission after first-line chemotherapy. METHODS: Serum levels of VEGF and D
      dimer were assessed by ELISA in 62 patients who completed first-line chemotherapy
      and underwent second-look laparotomy at Duke University Medical Center. Cox
      Proportional Hazards Modeling was utilized to determine if VEGF and/or D-dimer
      levels could predict disease-free and overall survival. The Kaplan-Meier method
      was used to estimate median survival. The Wilcoxon test was used to determine if
      a significant difference existed in median VEGF and D-dimer levels between
      patients with positive and negative second-look operations. RESULTS: Forty (65%)
      of the 62 women who underwent second-look laparotomy had persistent disease. The
      median VEGF levels were 264 pg/ml (range 109-896 pg/ml) in the group with
      negative second looks compared to 390 pg/ml (range 99-1011 pg/ml) in those with
      positive second-looks (P = 0.1). High levels of VEGF were marginally associated
      with the presence of persistent (P = 0.10) and gross (P = 0.07) disease at the
      time of second look laparotomy. After adjusting for CA125, women with high VEGF
      serum levels had a worse overall survival (P = 0.004). CONCLUSIONS: This study
      suggests that serum VEGF may be a clinically important marker for persistent
      disease and is predictive of survival in ovarian cancer patients after first-line
      chemotherapy.

PMID- 15262123
TI  - Kallikrein 4 is associated with paclitaxel resistance in ovarian cancer.
AB  - OBJECTIVE: Carcinoma of the ovary is the most fatal malignancy of the female
      genital tract in western countries. The effectiveness of chemotherapy is limited
      by the acquisition of drug resistance. Several members of the kallikrein (KLK)
      family were recently shown to be expressed in ovarian cancer and implicated in
      disease prognosis. One of these is KLK4, whose increased mRNA expression was
      identified as a poor prognostic marker in ovarian cancer. The goal of this study
      was to investigate if KLK4 protein (hK4) is expressed in ovarian carcinoma
      lesions and if it is associated with paclitaxel resistance. METHODS:
      Immunohistochemistry was used to assess hK4 expression. The 126 lesions were from
      a cohort of 46 patients with platinum-resistant tumors, which were treated with
      weekly paclitaxel for recurrent disease. The overall response rate to weekly
      paclitaxel was 52% (24 of 46) and for patients with tumors resistant to standard
      three weekly paclitaxel treatment 48% (16 of 33). RESULTS: Immunohistochemistry
      indicated that 85% (79 of 93) of lesions from paclitaxel-resistant patients
      expressed hK4, while only 61% (20 of 33) of lesions were positive for hK4 from
      paclitaxel sensitive patients. Statistical analysis showed that the intensity of
      hK4 staining was significantly associated with paclitaxel resistance (P = 0.005),
      whereas hK4 staining extent showed marginal significance (P = 0.05), but was
      significantly correlated with higher histological grade (P < 0.001). CONCLUSION:
      These data show that hK4 is expressed in ovarian cancer and suggest that hK4
      expression might be a predictive marker for paclitaxel resistance.

PMID- 15262124
TI  - The activity of thymidine phosphorylase as a new ovarian tumor marker.
AB  - OBJECTIVE: The aim of this study was to evaluate the thymidine phosphorylase (TP)
      activity of tumor cells and serum as a marker in patients with ovarian cancer.
      METHODS: The activity of TP was measured by the spectrophotometric method in the
      cytosol of ovarian tumor tissues from 47 patients after surgery, and in the
      presurgery serum from the same patients. Ten women with normal ovaries, treated
      surgically due to nononcological reasons served as a control. Microvessel density
      (MD) was evaluated in tumor using immunohistochemical methods. A relationship
      between TP activity and MD and clinicopathologic features was investigated.
      RESULTS: A significantly higher TP activity was stated both in malignant tumor
      and serum specimens from ovarian cancer patients when compared to the control. A
      positive correlation between the enzyme activity in the serum and neoplasmatic
      tissue was found. Neoangiogenesis is higher in ovarian cancer when compared to
      the group of borderline malignancy tumors but a reverse correlation between MD
      and TP activity in malignant tumors was observed. TP activity is significantly
      higher in more advanced neoplasmatic disease (FIGO III and IV) although no
      correlation between TP activity and grading or histopathological type of ovarian
      tumor was observed. CONCLUSION: Thymidine phosphorylase activity might be useful
      in diagnostic characterization of ovarian cancer.

PMID- 15262125
TI  - The physician-patient relationship before cancer treatment: a prospective
      longitudinal study.
AB  - OBJECTIVES: To evaluate quality of life before surgery for genital cancer to
      determine risk factors that might influence the physician-patient relationship.
      METHODS: From 1993 until 2003, 129 women with cervical cancer entered this
      prospective study. Patients were contacted 1 to 5 days before surgery by a
      psychologist or psychotherapeutically trained physician on the surgical ward. The
      semistructured interview included questions on the patient's psychosocial well
      being according to criteria of the biographic interview technique. The
      preoperative anxiety level was evaluated by the STAI and quality of life by the
      Cancer Rehabilitation Evaluation System (CARES) and EORTC questionnaires.
      Patients were assigned to groups undergoing pelvic exenteration (n = 62) or
      Wertheim procedure (n = 67). RESULTS: The preoperative anxiety level did not
      correlate with the treatment modality. Women with a high anxiety level complained
      of a lack of information which correlated with a dissatisfaction concerning the
      physician-patient relationship (r = 0.457, P = 0.001). Quality of life in terms
      of medical interaction and the need for information were indicated to be the most
      important aspects for cancer patients facing genital surgery. CONCLUSIONS: These
      data demonstrate the need for information strategies before surgery: first, to
      reduce anxiety by anticipating future quality of life outcome problems and,
      second, to improve medical interaction before stressful treatment options.

PMID- 15262126
TI  - Randomized Phase II trial of two high-dose chemotherapy regimens with stem cell
      transplantation for the treatment of advanced ovarian cancer in first remission
      or chemosensitive relapse: a Southwest Oncology Group study.
AB  - OBJECTIVES: To evaluate response rates, progression-free survival (PFS), overall
      survival (OS), and toxicity of two high-dose chemotherapy regimens with stem cell
      rescue used to treat patients with recurrent or persistent stage III/IV ovarian
      cancer, with the goal of taking one forward into a Phase III comparison with
      conventional therapy. METHODS: Patients under 65 with clinically or
      pathologically persistent disease after initial chemotherapy or those relapsing
      >6 months after a complete remission (CR) were randomized to CMC carboplatin
      (1500 mg/m(2)), mitoxantrone (75 mg/m(2)), and cyclophosphamide (120 mg/kg)], or
      CTC: [cisplatin (165 mg/m(2)), thiotepa (600 mg/m(2)), and cyclophosphamide (5625
      mg/m(2))] with stem cell rescue. RESULTS: Of 67 randomized, the 32 and 26
      eligible in the CMC and CTC arms were matched including age (median 49), maximum
      tumor diameter, and disease status at transplant. Low-risk disease (maximum
      diameter disease <or= 0.5 cm and platinum sensitivity) was demonstrated in only
      approximately one-half of the patients. There were two treatment-related deaths
      in each arm. The median PFS was 13 and 8 months, respectively, for the CMC and
      CTC arms. The median OS was 29 and 22 months for the CMC and CTC arms. In a
      multivariate analysis of PFS, normal CA125 at transplant and CR to primary
      therapy were significant; for OS, normal CA125 and platinum sensitivity were
      significant. CONCLUSIONS: The CMC regimen was the superior regimen. However, few
      patients were long-term progression-free survivors. A clinical CR to primary
      therapy and a normal CA125, seen in a minority of patients, were requirements for
      a favorable outcome.

PMID- 15262128
TI  - Loss of heterozygosity analysis in uterine cervical adenocarcinoma.
AB  - OBJECTIVE: Uterine cervical adenocarcinoma (CAC) is a rare form of cervical
      cancer, constituting only 5-8% of all cervical epithelial malignancies. Loss of
      heterozygosity (LOH) analysis of CAC was undertaken to identify alterations of
      chromosomal loci that may play important roles in the development of this tumor
      type. METHODS: We analyzed loss of heterozygosity (LOH) using a total of 50
      markers on 20 chromosomal arms in 37 cases of microdissected CAC DNA. RESULTS:
      LOH of >40% was observed on 2p (50%), 3p (45%), 9p (45%), 11q (46%), 17p (57%),
      17q (44%), 18q (57%), and 19p (44%). LOH of 30-40% was observed on 6p (38%), 6q
      (40%), and 10q (31%). Overall, mean LOH was 34% and fractional allelic loss (FAL)
      was 0.34. High-level and low-level microsatellite instability (MSI) was shown in
      four cases (11%) and six cases (16%), respectively. Frequency of LOH on10q was
      significantly higher in endometrioid-type than endocervical-type adenocarcinoma
      (71% versus 20%; P < 0.05). Conversely, 6q LOH was higher in endocervical type
      than endometrioid type (0% versus 60%; P < 0.05). 19p13.3 has been reported to be
      frequently deleted in adenoma malignum, a histological subtype of CAC. To define
      the critical regions of LOH in CAC in general, we further performed deletion
      mapping of 19p using 13 markers. Unlike adenoma malignum, multiple regions on 19p
      appeared to be important loci of LOH for CAC. CONCLUSION: CACs develop with
      frequent LOH of multiple chromosomal arms, which may be related to its aggressive
      clinical behavior and poor prognosis. LOH of 10q may be unique to endometrioid
      type CAC.

PMID- 15262127
TI  - Resistance to TRAIL-induced apoptosis in ovarian cancer cell lines is overcome by
      co-treatment with cytotoxic drugs.
AB  - BACKGROUND: TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a
      recently identified cytokine that preferentially kills transformed cells while
      sparing most normal cells. METHODS: We investigated the ability of TRAIL alone
      and TRAIL in combination with cytotoxic drugs to induce apoptosis in six ovarian
      cancer cell lines. To get some insight into the resistance to TRAIL, the
      expression of TRAIL receptors and selected downstream signaling elements was
      determined. RESULTS: TRAIL induced significant apoptosis (up to 80%) in three out
      of six ovarian cancer cell lines (MZ-26, CaOV-3, ES-2). In A2780 and A2780ADR
      cells, resistance to TRAIL-induced apoptosis correlated with their lack of DR4
      expression. MZ-15 cells, which expressed the processed form of FLIP(L), p43 (FADD
      like IL-1beta-converting enzyme (FLICE)-like inhibitory protein (FLIP)), and
      FLIP(S), were resistant to TRAIL in spite of the presence of DR4. When TRAIL
      resistant cell lines were co-incubated with routinely used cytotoxic agents,
      TRAIL exerted a synergistic effect leading to apoptosis rates unachievable by
      incubation with cytotoxic agents alone. CONCLUSION: The ability of TRAIL to
      induce apoptosis in ovarian cancer cells as well as to potentiate the activity of
      chemotherapeutic agents even in cell lines that are resistant to TRAIL-induced
      cytotoxicity is a powerful promise in the fight against this deadly disease.

PMID- 15262129
TI  - Evaluation of concurrent and adjuvant carboplatin with radiation therapy for
      locally advanced cervical cancer.
AB  - OBJECTIVE: To analyze the toxicity profile and long-term outcomes of patients
      receiving carboplatin with concurrent radiation for locally advanced cervical
      cancer. METHODS: A retrospective study was performed to identify patients treated
      with carboplatin and concurrent radiation therapy for locally advanced cervical
      cancer with a minimum follow-up period of 24 months. Records were reviewed for
      demographic data, chemotherapy doses, toxicities, and survival outcomes.
      Specifically reviewed were hematologic, gastrointestinal, and renal toxicities
      and the need for dose modification and treatment delays. RESULTS: Twenty-one
      patients with cervical carcinoma Stage IIB (7), III (13), or IVA (1) treated with
      carboplatin chemotherapy from 1993 to 2001 were identified. Carboplatin at a dose
      of 300 mg/m(2) administered every 3 weeks for an intended six courses was
      initiated at the start of radiation therapy. No grade 3 or 4 thrombocytopenia or
      renal toxicity was observed. Nine patients had delays in chemotherapy
      administration and/or received a 25% reduction in the dose of chemotherapy based
      on one or more of the following: thrombocytopenia (platelet count <100000
      cells/mcl) (n = 3), granulocytopenia (ANC <1.0) (n = 4), or anemia (hemoglobin
      <10.0 g/dl) (n = 5). The median carboplatin AUC was 3.9 (range 3.0-5.0). Six
      patients developed recurrent disease (five local and one distant) with a pelvic
      control rate of 76% and an overall survival of 71%. CONCLUSION: Carboplatin at a
      dose of 300 mg/m(2) (equivalent to an AUC of 3.9) on an every 3-week schedule is
      tolerable with concurrent pelvic radiation therapy for locally advanced cervical
      cancer. The efficacy of carboplatin, compared to cisplatin, as a radiation
      sensitizer can only be determined in a randomized clinical trial.

PMID- 15262130
TI  - Vascular endothelial growth factor (VEGF) and ovarian carcinoma cell supernatant
      activate signal transducers and activators of transcription (STATs) via VEGF
      receptor-2 (KDR) in human hemopoietic progenitor cells.
AB  - OBJECTIVE: To investigate the STATs signaling pathway activated by VEGF in human
      hemopoietic progenitor cells. METHODS: CD34(+) hemopoietic progenitor cells,
      which isolated from umbilical cord blood, were treated with VEGF or culture
      supernatant of ovarian carcinoma cell line which could secrete large amount of
      VEGF, phosphorylation and nuclear translocation of STAT3 and STAT5 were then
      detected by Western Blot and immunocytochemistry. Expression of VEGFR2/KDR on
      CD34(+) cells was studied by immunocytochemistry. The specific VEGFR2/KDR
      heptapeptide antagonist ATWLPPR was used to identify whether the activation of
      STATs signaling pathway was specifically mediated by VEGFR2/KDR. RESULTS: The
      concentration of VEGF in SKOV3-supernatant was 4024.84+/- 505.59 pg/ml. CD34(+)
      progenitor cells could express VEGFR2/KDR. When CD34(+) cells were stimulated by
      VEGF and SKOV3-supernatant, STAT3 appeared tyrosine-phosphorylation and nuclear
      translocation, but STAT5 was only phosphorylated, and not translocated. When
      ATWLPPR was used to block the binding of VEGF to KDR, VEGF and the SKOV3
      supernatant failed to activate the phosphorylation of STAT3 and STAT5.
      CONCLUSIONS: STAT3 may participate in the signal transduction pathways activated
      by VEGF specifically mediated by VEGFR2/KDR in human hemopoietic progenitor
      cells, and the aforementioned signaling pathway participated in the interaction
      of ovarian carcinoma cells and progenitor cells.

PMID- 15262131
TI  - Job satisfaction, stress, and burnout among Canadian gynecologic oncologists.
AB  - OBJECTIVES: (1). To provide a job description of Canadian gynecologic
      oncologists. (2). To assess job satisfaction and job stress, and measure the
      prevalence of burnout and psychological morbidity. METHODS: A cross-sectional
      survey was mailed to all Canadian gynecologic oncologists in September 2002.
      RESULTS: The job profile on Canadian gynecologic oncologists is predominantly
      clinical with a minor component of administration and to a less extent education
      or research. Clinically, 80% of the activity is focused on gynecologic cancer
      care. The majority of physicians (92%) are satisfied with their job, but there
      are clear concerns raised concerning systems issues in health care delivery.
      Approximately 26% of physicians are experiencing high stress, and this is
      strongly associated with emotional exhaustion and high depersonalization.
      Fourteen percent of Canadian gynecologic oncologists are actively looking for
      alternative jobs and 45% are trying to decrease the number of hours worked per
      week. When considering an alternate job, the most important factors are location,
      colleagues, and potential for personal growth. CONCLUSION: High stress and low
      personal accomplishment were seen in Canadian gynecologic oncologists.
      Organizations (i.e., hospitals) and health care funders have the opportunity to
      incorporate preventative strategies to keep this physician resource healthy.

PMID- 15262132
TI  - Use of an ureteroileocecal appendicostomy urinary reservoir in patients with
      recurrent pelvic malignancies treated with radiation.
AB  - OBJECTIVE: Evaluation of a modified right colon urinary reservoir in a heavily
      radiated patient population undergoing pelvic exenteration. METHODS: A
      retrospective chart review was performed on all patients with recurrent
      gynecologic, colorectal, and urological tumors who underwent total pelvic or
      anterior exenteration and urinary diversion from 3/01 to 7/03 using an
      ureteroileocecal appendicostomy urinary reservoir. RESULTS: Fourteen patients
      were identified over the study interval. The mean age of the patients was 53
      years (range, 22-78 years). All patients received external beam, intracavitary,
      or a combination of both radiation treatment modalities to the pelvis
      preoperatively. Eight patients received intraoperative radiation therapy (IORT)
      at a mean dose of 16.25 Gy (range, 12.5-17.5 Gy). The primary sites of disease
      were as follows: cervix, five; prostate, three; uterus, two; colon/rectum two;
      and one each for vulva and bladder. Complete stomal continence was achieved in
      all patients after a median follow-up of 10 months (range, 2-31 months). Two
      patients experienced a traumatic disruption of the stomal-skin anastomosis in the
      early postoperative period (postoperative days 7 and 14). One late complication
      related to the ureterointestinal anastomosis was observed and consisted of an
      anastomotic stricture managed conservatively. One patient experienced an entero
      pouch fistula following re-exploration for an acute postoperative hemorrhage.
      CONCLUSION: The early outcomes using the ureteroileocecal appendicostomy urinary
      reservoir in heavily radiated patients demonstrate the technical feasibility of
      this design as both minimal early stoma and ureterointestinal complications may
      occur. Longer postoperative follow-up will be required to address the late
      outcomes of this procedure and its ultimate use in this population.

PMID- 15262133
TI  - Cardiac safety profile of prolonged (>or=6 cycles) pegylated liposomal
      doxorubicin administration in patients with gynecologic malignancies.
AB  - OBJECTIVE: Pegylated liposomal doxorubicin (PLD) is currently utilized in the
      management of several solid tumors. While PLD has been shown to be less
      cardiotoxic than doxorubicin, the safety of prolonged administration (e.g., >or=6
      cycles) of the agent remains undefined. METHODS: A retrospective chart review was
      performed of the Cleveland Clinic experience from 1997 to 2003 with the prolonged
      (>or=6 cycles) use of PLD in individuals with gynecologic malignancies. PLD was
      administered at doses ranging from 20 to 40 mg/m(2) (infused over 1-2 h) with
      treatment repeated every 4-6 weeks. While on therapy, patients underwent routine
      evaluation for toxicity, including the performance of multigated acquisition
      (MUGA) scans for determination of left ventricular ejection fraction (LVEF).
      RESULTS: Twenty-two patients (18 ovarian cancer; 3 primary peritoneal cancer, 1
      endometrial cancer) met the criteria for inclusion in this analysis. This
      population had received a median of 4 (range 1-8) chemotherapy regimens before
      initiation of PLD. No patient had previously received doxorubicin. The median
      number of PLD cycles and cumulative dose of LD delivered were 8 (range 6-26) and
      483 mg/m(2) (256-1699 mg/m(2)), respectively. One or more MUGA scans were
      obtained in 14 (64%) patients. No patient experienced clinical evidence (physical
      findings, symptoms) of heart failure. There were no dose reductions due to
      cardiac dysfunction, and no patient experienced a decline in LVEF to <50%, or a
      >or=10% reduction compared to a baseline value. CONCLUSIONS: Prolonged therapy
      with PLD is possible in appropriately selected patients with advanced gynecologic
      malignancies. In this clinical setting, cardiac dysfunction does not appear to be
      a toxicity, which limits the duration of treatment. The development of evidence
      based guidelines for monitoring cardiac function in this patient population would
      be quite useful.

PMID- 15262134
TI  - RNA expression of MDR1/P-glycoprotein, DNA-topoisomerase I, and MRP2 in ovarian
      carcinoma patients: correlation with chemotherapeutic response.
AB  - OBJECTIVE: Clinical drug resistance is the major obstacle in the successful
      treatment of ovarian cancer. Besides elevated expression of adenosine
      triphosphate binding cassette (ABC) transporters, such as MDR1/P-gp or
      MRP2/cMOAT/ABCC2, alterations in the expression of DNA topoisomerase I (TOP1) are
      associated with drug-resistant phenotypes in various model systems. METHODS: In
      ovarian specimens of 61 patients, the mRNA expression levels of MDR1/P-gp, MRP2,
      and TOP1 were determined using a competitive quantitative RT-PCR protocol with
      internal standards. The mRNA expression levels were correlated with the clinical
      outcome and histopathological criteria. The tumor specimens included 11/61 (18%)
      benign ovarian tumors, including 2 LMP tumors, and 50/61 (82%) ovarian
      carcinomas, including 34 primary and 16 recurrent cancers. Moreover, 20/61 (33%)
      ovarian specimens showed low or no MDR1/P-gp expression. RESULTS: None of the
      benign tumors showed MRP2 expression, whereas 15/50 (30%) ovarian carcinomas
      expressed MRP2. In 61/61 (100%) of the samples, expression of TOP1 could be
      measured. In patients with recurrent ovarian cancer, no differences in expression
      of any of the factors could be observed. In patients with primary FIGO III
      carcinomas (n = 18), the overall-survival time (OST) was significantly prolonged
      with low MDR1/P-gp expression level (P = 0.015). Expression levels of MRP2 and
      TOP1 did not correlate with OST. Moreover, the progression-free survival (PFS) in
      FIGO III patients showed a clear tendency to be associated with low MDR1/P-gp (P
      = 0.218) and TOP1 expression (P = 0.466), and negativity for MRP2 (P = 0.244).
      CONCLUSION: MDR1/P-gp and MRP2 might have some additional predictive value for
      the clinical outcome of patients with advanced ovarian carcinoma.

PMID- 15262135
TI  - Lymphatic mapping and sentinel node identification as related to the primary
      sites of lymph node metastasis in early stage ovarian cancer.
AB  - OBJECTIVE: We evaluated the primary sites of lymph node (LN) metastasis in
      patients during the early stage of ovarian cancer. METHODS: Study 1: patients
      with clinical stage I and II common epithelial ovarian carcinoma (n = 150)
      underwent systematic retroperitoneal LN dissection of the pelvic and paraaortic
      areas. The relationship between the incidence and location of LN metastasis and
      clinical and histological characteristics was examined. Study 2: we studied 11
      women with endometrial or fallopian tube tumors. At laparotomy, activated
      charcoal solution was injected into the unilateral cortex of the ovary. Ten
      minutes later, the retroperitoneal spaces were opened and charcoal uptake within
      the pelvic lymph node (PLN) and paraaortic node (PAN) as far as the level of
      renal vein was examined. RESULTS: Study 1: The incidence of LN metastasis by
      stage was 6.5% (8/123) in stage I and 40.7% (11/27) in stage II. Among 19
      patients with LN metastasis, 14 had only PAN, 2 had only pelvic LN, and 3 had
      both PAN and PLN metastases. Metastasis was limited to the ipsilateral side in 12
      (63%) patients, but was bilateral in 5 (26%) and contralateral to the neoplastic
      ovary in 2 (11%). Positive peritoneal cytology was significantly (P < 0.05)
      correlated with lymph node metastasis. Study 2: Lymphatic channels along the
      ovarian vessels were identified in all injected ovaries. Charcoal was deposited
      in the LN of all patients. The locations of these nodes included PAN in all
      patients, common iliac node in three, and external iliac node in one. CONCLUSION:
      PAN is the primary site of LN metastasis in ovarian cancer. Bilateral PAN
      dissections are necessary to determine the extent of tumors even in stage I
      ovarian carcinoma.

PMID- 15262136
TI  - Prevalence of bladder tumors in women referred with postmenopausal bleeding.
AB  - OBJECTIVES: The aim of this study is to identify the prevalence of urinary
      bladder (UB) tumors in women presenting with postmenopausal bleeding (PMB). STUDY
      DESIGN: A prospective cohort study. New patients presenting for the PMB clinic in
      the period June 2002-June 2003 underwent transvaginal ultrasound scan (TVUS). All
      cases where bladder pathology was identified during TVUS were referred for
      urological opinion. Cystoscopy was undertaken in all cases and subsequent
      histological examination was carried out. MAIN OUTCOME MEASURES: Benign and
      malignant urinary bladder tumors. RESULTS: Two hundred eighty new referrals were
      reviewed in the PMB clinic. Three cases of UB tumors were identified on TVUS,
      none of them had an endometrial pathology and all cases had subsequent cystoscopy
      that confirmed the TVUS findings and resection of the bladder tumors was
      undertaken. Histological examination revealed one benign and two malignant
      urinary bladder tumors that were all completely excised. CONCLUSION: The
      prevalence of bladder tumors in women presenting with PMB in our population was
      found to be 1.07%, and the prevalence of bladder cancer was 0.7%.

PMID- 15262137
TI  - The role of optimal debulking in advanced stage serous carcinoma of the uterus.
AB  - OBJECTIVE: To evaluate the role of optimal surgical cytoreduction and
      postoperative therapy in women with advanced uterine serous carcinoma (USC).
      METHODS: A multi-institutional, retrospective review identified 52 women with
      stage IV USC. Patient factors, surgical findings, and follow-up data were
      collected. Differences in demographics, surgical treatments, and adjuvant
      therapies administered were assessed with Fisher's exact test. Analysis of
      survival was performed using Kaplan-Meier and comparisons of survival were made
      using the log-rank test. RESULTS: Twenty-six women were optimally debulked (<or=1
      cm residual) and 23 were suboptimally debulked. Three women underwent biopsies
      for pathologic confirmation and were included in the suboptimal group. There was
      no difference in demographic characteristics, clinical symptoms, postoperative
      complications, or mortality between the two groups. Median CA-125 level at
      presentation was not statistically different between the two groups (P > 0.05).
      Median survival was longer in the optimal group (15 vs. 8 m), however, this did
      not reach statistical significance (P > 0.05). Women who received adjuvant
      platinum-based chemotherapy had a longer median survival than those who did not
      receive platinum chemotherapy (21 vs. 2 m) (P < 0.0001). Optimal cytoreduction
      combined with adjuvant therapy demonstrated a trend toward prolonged survival
      when compared to suboptimal cytoreduction combined with adjuvant therapy.
      However, the results did not achieve statistical significance (P > 0.05).
      CONCLUSION: Although no clear survival advantage is shown in the women who
      underwent optimal versus suboptimal debulking, there was a trend towards longer
      median survival in those who were maximally cytoreduced. Adjuvant platinum-based
      chemotherapy is associated with significantly longer survival in all women,
      regardless of amount of residual disease.

PMID- 15262138
TI  - Value of intraoperative imprint cytology of sentinel nodes in patients with
      cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate intraoperative imprint
      cytology (IC) for the detection of sentinel node (SN) involvement in patients
      with cervical cancer. METHODS: Thirty-six consecutive patients with cervical
      cancer underwent a laparoscopic SN procedure with intraoperative IC, followed by
      complete laparoscopic pelvic lymphadenectomy, with or without laparoscopic para
      aortic lymphadenectomy. The SN was bisected and both cut surfaces were applied to
      the surface of glass slides. Permanent sections were stained with H&E and
      immunohistochemical methods. The IC results were compared with the final
      histological results. RESULTS: At least one SN (mean: 2 SN per patient, range: 1
      5) was detected in 34 of the 36 patients. Eight patients (22.2%) had a total of
      12 metastatic SNs (four macrometastatic, five micrometastatic, and three with
      isolated tumor cells). No false-negative results of SN biopsy were obtained. Only
      one metastasis was identified by IC. No false-positive findings were obtained
      with IC. The overall sensitivity, specificity, accuracy, and positive and
      negative predictive values of IC were 8.3%, 100%, 85.7%, 100%, and 85.5%,
      respectively. CONCLUSION: These results suggest that intraoperative imprint
      cytology of sentinel nodes is unreliable in patients with cervical cancer.

PMID- 15262140
TI  - Management of patients with metastatic gestational trophoblastic tumor.
AB  - OBJECTIVE: This study was designed to analyze the results of treatment on
      patients with metastatic gestational trophoblastic tumor (metastatic GTT).
      METHOD: During 1996-2001, 38 cases with metastatic GTT were diagnosed and
      received treatment in Vali-e-Asr Hospital, Tehran, Iran. Data were gathered
      retrospectively and analyzed based on therapy and response rate. Sixteen patients
      initially labeled as low-risk, four as middle-risk and eighteen as high-risk
      patients according to FIGO scoring system (1992). Thirty-four (89.5%) patients
      responded to treatment; 13 to single-agent [methotrexate (MTX) or ACT] and 21 to
      multiagent chemotherapy [EMA/cisplatinum and etoposide (EMA-EP) or MTX, ACT-D and
      cyclophosphamide or chlorambucil (MAC)]. RESULTS: All low-risk patients, 2 middle
      risk patients and 16 high-risk patients responded to treatment. Four cases failed
      to respond to therapy due to CNS involvement. CONCLUSIONS: Patients with low-risk
      metastatic GTT have a 100% chance to response to single-agent chemotherapy and
      those with high-risk disease have great chance to response to multiagent
      chemotherapy such as EMA-EP.

PMID- 15262139
TI  - HPV DNA test and Pap smear in detection of residual and recurrent disease
      following loop electrosurgical excision procedure of high-grade cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: We compared the performance of cervical cytology and HPV DNA test in
      detection of residual or recurrent disease following the treatment of cervical
      intraepithelial neoplasia (CIN) 2/3 with loop electrosurgical excision procedure
      (LEEP). SUBJECTS AND METHODS: A series of 107 women subjected to LEEP due to
      histologically confirmed CIN 2/3 between March 2001 and December 2002 were
      followed-up biannually until January 2004. Follow-up visits consisted of
      interview and gynecological examination including cervical cytology, hybrid
      capture II (HCII), and colposcopy. Patients presenting with abnormal colposcopy
      or high-grade squamous intraepithelial lesion (HSIL) smear were subjected to new
      excision procedure, and presence of histologically confirmed CIN 2/3 or higher
      was considered as residual or recurrent disease. Performance indicators were
      calculated for cytology and HCII assay in detecting residual or recurrent
      disease. RESULTS: Eleven (10.2%) women showed residual or recurrent disease
      during the follow-up. Considering HCII and Pap smear as stand-alone tests, both
      techniques showed similar sensitivity, detecting 100% of CIN 2/3 at the first
      follow-up visit. At the second follow-up visit, Pap smear showed better
      specificity and positive predictive value (PPV) than HCII, and both tests had
      fairly the same high negative predictive value (NPV) and sensitivity. The
      combined positive HCII and abnormal cytology had the same sensitivity as each of
      the tests alone, but specificity and PPV were significantly higher than those of
      single tests. When only one of the tests was positive, the sensitivity and the
      NPV of the combination remained the same, but its specificity and PPV were lower
      than that of the combined two positive tests and that of the individual test, at
      both follow-up visits. CONCLUSIONS: Both tests performed well in detecting
      residual or recurrent disease after LEEP and combination of the tests did not
      increase sensitivity of the single tests.

PMID- 15262141
TI  - Limitations of adjuvant radiotherapy for uterine sarcomas spread beyond the
      uterus.
AB  - OBJECTIVE: The present review analyzes patients with advanced uterine sarcomas
      with the goal of identifying patients likely to benefit from larger volumes and
      higher dosages of radiotherapy. METHODS: A retrospective review was performed of
      medical records of all patients receiving adjuvant radiotherapy for advanced
      uterine sarcomas from 1978 to 1997 at the University of Minnesota. RESULTS:
      Nineteen women with advanced uterine sarcomas received adjuvant radiotherapy.
      Seven also received adjuvant chemotherapy. Three patients had FIGO stage IIIA, 1
      stage IIIB, 5 stage IIIC, and 12 stage IVB. Patients with mixed mullerian tumors
      had overall and disease-free survivals of 31% at 1 year and 23% at 5 years. For
      leiomyosarcomas, overall survival was 67% at 1 year and 33% at 5 years, but
      relapse-free survival was 33% at 1 and 5 years. First sites of failure were three
      pelvic and abdominal, one abdominal only, one abdominal and distant, two pelvic
      and distant, one pelvic, abdominal, and distant, five distant only, and one
      unknown. No Grade 3 or 4 toxicity occurred. CONCLUSION: Ongoing technical
      advancements in radiotherapy offer more precise radiation delivery, particularly
      to the peritoneal cavity. Although abdominal failures are common in women with
      mixed mullerian tumors, translation of higher radiation dosage to cure is
      unproven, and the majority of failures have a distant component. Until effective
      systemic therapy is developed, the prognosis of uterine sarcomas with any spread
      beyond the uterus will remain poor.

PMID- 15262143
TI  - Single-agent pulse dactinomycin has only modest activity for methotrexate
      resistant gestational trophoblastic neoplasia.
AB  - OBJECTIVES: To determine the effectiveness of single-agent pulse dactinomycin for
      methotrexate-resistant low-risk gestational trophoblastic neoplasia (GTN).
      METHODS: Ten patients with low-risk GTN (WHO/FIGO score <8) previously treated
      with uterine evacuation and single-agent methotrexate were treated with pulse
      dactinomycin 1.25 mg/m(2) every 2 weeks. RESULTS: Patients had antecedent
      pregnancies of complete mole (7), partial mole (1), missed abortion (1), and
      choriocarcinoma (1). One patient underwent hysterectomy during methotrexate
      treatment. The mean hCG level and WHO score before dactinomycin was 1476 and 4.1,
      respectively. Six of 10 (60%) patients achieved complete remission with single
      agent pulse dactinomycin. Two others responded to a 5-day regimen of
      dactinomycin, 1 responded to a multidrug regimen, and 1 had chemo-resistant
      disease dying of metastatic choriocarcinoma. After median follow-up of 11.9
      months, 9 of 10 patients remain without relapse. A mean of 3.3 (1-6) cycles were
      given-4.5 (3-6) for responders and 1.5 (1-2) for nonresponders. In 33 cycles of
      chemotherapy administered, there were 46 toxicity events: all events were graded
      as 1. While WHO scores were comparable between responders and nonresponders (mean
      3.8 vs. 4.5), hCG levels were lower in responders (mean 37 vs. 3634) but the
      sample size was too small to reach statistical significance. CONCLUSIONS:
      Although remission rates of 80-90% have been reported for pulse dactinomycin,
      patients with methotrexate-resistant GTN had only a 60% remission rate.
      Prediction of remission may be more closely associated with hCG levels than with
      WHO score alone.

PMID- 15262142
TI  - Pure-type clear cell carcinoma of the ovary as a distinct histological type and
      improved survival in patients treated with paclitaxel-platinum-based chemotherapy
      in pure-type advanced disease.
AB  - OBJECTIVE: The aim was to compare survival in pure and mixed-type advanced clear
      cell ovarian carcinoma and to determine the benefits among patients with pure
      advanced clear cell ovarian carcinoma treated in paclitaxel-platinum-based
      chemotherapy in comparison with those treated in conventional platinum-based
      chemotherapy after primary surgery. METHODS: Between 1994 and 2001, 31 women with
      stage III and IV pure clear cell ovarian carcinoma and nine patients with stage
      III and IV mixed-type clear cell carcinoma were identified from the tumor
      registry of six institutions. All patients underwent cytoreductive surgery
      followed by conventional platinum-based chemotherapy or paclitaxel and platinum
      based chemotherapy. RESULTS: The median survival of women with pure clear cell
      carcinoma was 11 months, compared to 48+ months for those with mixed-type clear
      cell carcinoma (P = 0.003). Overall, for women with pure clear cell carcinoma,
      35% had clinically complete responses to chemotherapy. For women with pure clear
      cell carcinoma treated with paclitaxel-platinum-based chemotherapy, the median
      survival was significantly longer than for those treated with conventional
      platinum-based chemotherapy (16.26 vs. 10.75 months, P = 0.045; with optimal
      cytoreduction, 40.95 vs. 9.02 months, P = 0.028). Univariate analysis showed
      paclitaxel-platinum-based treatment was the only favorable prognostic factor for
      women with advanced pure clear cell ovarian carcinoma (P = 0.05). CONCLUSIONS:
      Patients with advanced pure clear cell ovarian carcinoma have poorer prognoses
      than those with the mixed type. Paclitaxel-platinum-based chemotherapy improved
      survival among our patients with advanced pure clear cell carcinoma, especially
      for those with optimal cytoreduction.

PMID- 15262144
TI  - Association between uterine serous carcinoma and breast cancer.
AB  - OBJECTIVE: Endometrial cancer and breast cancer are two common malignancies found
      in women. As a result of estrogen dependency, an association is thought to exist
      between these entities. This study was undertaken to determine if the endometrial
      carcinomas, which develop in women with a history of breast cancer, were more
      likely to be of the endometrioid or the serous histology, which is generally
      considered non-estrogen-dependent. METHODS: A retrospective chart review was
      conducted for the years 1984-2001. All women who were diagnosed at our
      institution with endometrial carcinoma were identified. The women who also had a
      prior history of breast cancer were identified and comprise the cohort for this
      study. Information regarding age at diagnosis, tumor stage, histologic subtype,
      and tamoxifen exposure were recorded and analyzed. RESULTS: About 1166 women were
      diagnosed with endometrial cancer during the study period, of whom 54 (4.6%) had
      a pre-existing diagnosis of breast cancer. Of the 54 women in this study, 41 had
      tumors of the endometrioid histology and 13 had a tumor of the serous subtype.
      There was no difference with regards to median age at the time of diagnosis or
      years of tamoxifen exposure. Women with breast cancer were more likely to develop
      uterine serous carcinoma (USC) as compared to one of endometrioid histology (OR
      2.6; 95% CI 1.29-5.23). CONCLUSIONS: Women with breast cancer who subsequently
      developed endometrial cancer exhibited a 2.6-fold increased risk of developing a
      USC as compared to an endometrioid carcinoma. These findings suggest that there
      may be an underlying genetic predisposition linking breast cancer and USC.

PMID- 15262145
TI  - Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic
      and symptomatic women.
AB  - OBJECTIVE: To determine the ability of whole-body [(18)F]fluoro-2-deoxyglucose
      (FDG) positron emission tomography (PET) scan to detect recurrent cervical
      carcinoma in both symptomatic and asymptomatic women. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 44 women previously treated for cervical
      cancer who underwent 47 posttreatment whole-body FDG PET scans in an attempt to
      detect recurrent disease. Twenty-six scans were performed in asymptomatic women,
      whereas 21 scans were performed in women with symptoms suggestive of recurrence.
      RESULTS: About 30.8% of asymptomatic women had recurrent disease detected by PET
      scan compared to 66.7% of women in the symptomatic group. The sensitivity of PET
      scan for recurrent disease in asymptomatic women was 80.0%, specificity of 100%,
      a positive predictive value of 100%, and a negative predictive value of 88.9%.
      For symptomatic women, the sensitivity of PET was 100%, specificity of 85.7%, a
      positive predictive value of 93.3%, and a negative predictive value of 100%.
      CONCLUSIONS: The whole-body FDG PET scan is a sensitive imaging modality for the
      detection of recurrent cervical carcinoma in both symptomatic and asymptomatic
      women.

PMID- 15262146
TI  - Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant
      proliferation in intraepithelial neoplasia of the vulva.
AB  - OBJECTIVE: The mature eukaryotic translation initiation factor 5A contains the
      unusual amino acid hypusine, formed post-translationally from a specific lysine
      residue and essential for proliferation of eukaryotic cells. We hypothesized that
      the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH
      353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was
      used to test this proposal in biopsies of vulvar high-grade intraepithelial
      neoplasia (VIN), characterized by the presence of proliferating cells throughout
      the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded
      archival samples with an independently established diagnosis of VIN 3 were
      stained immunohistochemically after antigen retrieval, employing NIH-353 and, for
      comparison, the standard Ki-67 antibody. RESULTS: NIH-353 labeled neoplastic
      keratinocytes throughout the thickness of the epithelium in all VIN 3 samples.
      Malignant cells in a case of focally invasive squamous cell carcinoma also
      stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to
      these lesions, though still of apparently normal morphology, was immunoreactive
      throughout its full thickness. At inflammatory foci of lesional sites, solitary
      reactive lymphocytes were positive, as were individual proliferating cells within
      dermal appendages. The submucosal stroma lacked reactive cells. CONCLUSION: NIH
      353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki
      67, this immunoreagent promises broad applicability in histopathological
      diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353
      visualizes a molecular target for antineoplastic therapy, and thus may guide the
      development and clinical testing of drugs that, like the fungicide ciclopirox,
      inhibit hypusine formation and cell proliferation.

PMID- 15262147
TI  - Bilateral ovarian fibromatosis presenting with ascites and hirsutism.
AB  - BACKGROUND: Ovarian fibromatosis is a very rare nonneoplastic disease. Due to the
      rarity and atypical clinical presentations, they may give rise to a misdiagnosis
      of malignancy and unnecessary extensive surgical interventions. Literature lacks
      definitive data about this rare disease and its preoperative evaluations. MRI
      together with the intraoperative frozen section may help us to define the benign
      nature of the disease. In this report, we aimed to review the literature and give
      a highlight to the gynecologic oncologists about this rare disease. CASE HISTORY:
      A 19-year-old female patient admitted to our hospital with the complaints of
      menstrual irregularity, hirsutism, and increased abdominal girth. Physical
      examination revealed bilateral ovarian mass, hirsutism, and ascites. Serum CA-125
      levels were slightly elevated. Preoperative MRI study showed bilateral
      hypointense lobulated ovarian masses. With the initial diagnosis of ovarian
      tumor, we performed explorative laparotomy and excised both masses. Final
      pathology was reported as bilateral ovarian fibromatosis. CONCLUSION: Ovarian
      fibromatosis commonly presents with ascites and solid pelvic mass and can be
      misdiagnosed as a malignant ovarian tumor. In young patients, clinicians should
      consider ovarian fibromatosis in differential diagnosis of pelvic mass.
      Preoperative MRI findings and intraoperative frozen examination may be used to
      avoid unnecessary aggressive surgical management.

PMID- 15262148
TI  - Pseudo-Meigs' syndrome associated with malignant struma ovarii: a case report.
AB  - BACKGROUND: Malignant struma ovarii is a rare tumor, consisting of a struma
      ovarii with malignant transformation. The association of a malignant struma
      ovarii with pseudo-Meigs' syndrome and elevated Ca-125 levels has been never
      reported. CASE: A 66-year-old woman presented with monolateral ovarian mass,
      ascites, hydrothorax, and elevated Ca-125 levels. Optimal medical staging was
      performed. Definitive histological examination revealed a malignant struma
      ovarii. The immediate and complete resolution of symptoms and rapid decline of
      both Ca-125 and thyroglobulin levels to normal value were achieved post
      operatively. After counseling, strict follow-up was planned, and no adjuvant
      therapy was administered. CONCLUSION: We report the first case of pseudo-Meigs'
      syndrome associated with malignant struma ovarii and elevated Ca-125 levels. The
      choice of not performing adjuvant therapy is feasible after optimal surgery and
      adequate staging procedure given to the usually clinical benign course and the
      low incidence of metastases in malignant struma ovarii. Careful patient
      counseling is required.

PMID- 15262149
TI  - Color Doppler ultrasound in ovarian fibrosarcoma.
AB  - BACKGROUND: Primary ovarian fibrosarcoma is a very rare tumor. Its Doppler
      waveform characteristics have not been described before. CASE: A 35-year-old
      woman presented with a 5-cm solid ovarian mass. Intratumoral artery resistance
      index (RI) and pulsatility index (PI) were very low (0.19 and 0.21,
      respectively). Peak systolic velocity calculated by using transvaginal Doppler
      ultrasound was higher than expected (24.8 cm/s). Postoperatively, the
      histopathologic diagnosis was primary ovarian fibrosarcoma, stage Ia.
      CONCLUSIONS: Low vascular resistance can be encountered in ovarian fibrosarcomas.
      In young patients presenting with a solid adnexal mass, intratumoral Doppler
      waveform investigations might offer some help for earlier prediction of rare
      malignant tumors like fibrosarcomas.

PMID- 15262150
TI  - Endometrial clear cell carcinoma metastatic to the paranasal sinuses: a case
      report and review of the literature.
AB  - BACKGROUND: Paranasal sinus metastasis following endometrial carcinoma is
      extremely rare and a reflection of disseminated disease. CASE: We report a case
      of a 72-year-old woman who presented ethmoid and sphenoid sinus metastasis, 14
      months after total abdominal hysterectomy and bilateral salpingo-oophorectomy due
      to an endometrial clear cell carcinoma. CONCLUSION: One should recognize the
      possibility of a metastatic disease to the sinuses in patients presenting with
      associated symptoms.

PMID- 15262151
TI  - Commenting on "future directions in the surgical management of ovarian cancer" by
      Berman 90:s35-39.

PMID- 15262152
TI  - Commenting on "future directions in the surgical management of ovarian cancer".

PMID- 15262154
TI  - Exposure-response functions for health effects of ambient air pollution
      applicable for China -- a meta-analysis.
AB  - Assessing the benefits of projects and policies to reduce air pollution requires
      quantitative knowledge about the relationship between exposure to air pollution
      and public health. This article proposes exposure-response functions for health
      effects of PM10 and SO2 pollution in China. The functions are based on Chinese
      epidemiological studies, and cover mortality, hospital admissions, and chronic
      respiratory symptoms and diseases. We derive the following coefficients for acute
      effects: a 0.03% (S.E. 0.01) and a 0.04% (S.E. 0.01) increase in all-cause
      mortality per microg/m3 PM10 and SO2, respectively, a 0.04% (S.E. 0.01) increase
      in cardiovascular deaths per microg/m3 for both PM10 and SO2, and a 0.06% (S.E.
      0.02) and a 0.10% (S.E. 0.02) increase in respiratory deaths per microg/m3 PM10
      and SO2, respectively. For hospital admissions due to cardiovascular diseases the
      obtained coefficients are 0.07% (S.E. 0.02) and 0.19% (S.E. 0.03) for PM10 and
      SO2, respectively, whereas the coefficients for hospital admissions due to
      respiratory diseases are 0.12% (S.E. 0.02) and 0.15% (S.E. 0.03) for PM10 and
      SO2, respectively. Exposure-response functions for the impact of long-term PM10
      levels on the prevalence of chronic respiratory symptoms and diseases are derived
      from the results of cross-sectional questionnaire surveys, and indicate a 0.31%
      (S.E. 0.01) increase per microg/m3 in adults and 0.44% (S.E. 0.02) per microg/m3
      in children. With some exceptions, Chinese studies report somewhat lower exposure
      response coefficients as compared to studies in Europe and USA.

PMID- 15262155
TI  - Gender-related difference, geographical variation and time trend in dietary
      cadmium intake in Japan.
AB  - OBJECTIVES: The present analysis was initiated to examine possible gender
      dependency, geographic variation, and time-dependent changes in dietary intake of
      cadmium (Cd-F) among general populations in Cd-non-polluted areas in Japan. The
      role of rice as Cd-F source was also within the scope. METHODS: Two databases on
      Cd and nutritional analyses were re-visited. Both databases were established
      through collection of 24-h food duplicate portion samples from residents in areas
      with no known Cd pollution, and contained information on Cd and energy contents
      in the duplicate portion, together with daily rice consumption, the gender, the
      age and the location of the residence of each sample donor. The first and the
      second databases were established through surveys in the years around 1980 on 564
      cases and around 1995 on 702 cases, respectively. The two databases were combined
      for evaluation by multiple regression (MRA) and other analyses. RESULTS: The
      analyses showed that men tended to take more Cd than women, more clearly so in
      the 1980 survey than in the 1995 survey. When Cd-F in the 1995 survey was
      compared with that in the 1980 survey, a substantial decrease was observed, e.g.
      by 30% (from 37.5 to 26.2 microg/day) in case of women. Cd-F values varied
      subject to the survey sites in a wide range (e.g. from 20 to 86 microg/day among
      women in the 1980 survey). In MRA with Cd-F as a dependent variable and survey
      sites and food intake factors (e.g. rice and energy intakes) as independent
      variables, the survey sites could explain more than 53% and 35% of total
      variation in Cd-F in the 1980 and 1995 surveys, respectively. Rice consumption
      was also influential to Cd-F in both surveys with partial correlation
      coefficients of 0.36 and 0.21, respectively, the influence being stronger in the
      1980 survey than in the 1995 survey. A significant correlation was detected
      between the 1980 and 1995 survey results both in Cd-F and in rice consumption.
      CONCLUSION: Geographic and gender-related differences, and time-dependent
      decrease in dietary Cd intake in Japan were detected through analyses of food
      duplicate-based databases. The leading role of rice as dietary Cd source was also
      observed.

PMID- 15262156
TI  - Influence of copper fungicide residues on occurrence of earthworms in avocado
      orchard soils.
AB  - The compost worm Eisenia fetida was used to demonstrate the avoidance by worms of
      Cu contaminated soil. Soils were collected from two avocado orchards in north
      eastern New South Wales, Australia. In avoidance trials, worms preferred non
      contaminated control soils, sourced from adjacent to the orchard or an OECD
      control soil, when Cu residues in the orchard soils reached 4-34 mg Cu kg(-1). At
      levels of 553 mg Cu kg(-1), 90% avoidance of orchard soil was observed. The worms
      showed preference for the soils in the order; uncontaminated field derived soil
      >OECD standard soil >Cu contaminated orchard soil. It was demonstrated that OECD
      standard soil was less favoured by worms than control soil derived from the test
      sites. While Cu was found to be the primary influence on worm avoidance in
      orchard soil, other factors, such as elevated soil Zn concentrations, could not
      be discounted. In a corresponding field study, it was shown that earthworms
      occurred at lower density in orchard soils with a history of Cu fungicide use. In
      one such orchard, soil Cu concentrations of up to 270 mg kg(-1) were determined
      and no earthworms were found, while nearby control sites and less contaminated
      sites within the orchard had up to 40.7 g m(-2) earthworm biomass. Considering
      the potential for Cu to accumulate in these soils and the subsequent impacts on
      soil biota, our results highlight the importance of limiting future application
      of Cu based fungicides.

PMID- 15262157
TI  - Geographic patterns of elemental deposition in the Aegean region of Turkey
      indicated by the lichen, Xanthoria parietina (L.) Th. Fr.
AB  - Lichen samples from different parts of the world have been known to accumulate
      elements to a greater degree than higher plants, if they are exposed to these
      elements from the atmosphere or from water and sediments. It has been
      hypothesized that lichens can be used to monitor air pollution around point and
      area emission sources. Local variation (variation in substrate, age and
      morphology of lichen samples) of element concentrations would not be large enough
      to affect the concentration patterns in large areas. We tested this hypothesis in
      the Aegean region of Turkey, which is very urbanized and industrialized. No such
      study has been conducted before in this part of the country. A total of 234
      samples of the lichen Xanthoria parietina were collected from a 51,800-km2 area.
      Samples were washed and analyzed by INAA and ICP-AES for 35 elements. The range
      of the concentrations for most of the elements on a local scale was an order of
      magnitude lower than for the element concentrations on a regional scale. The mean
      local coefficient of variance (CV) was found to be 15, providing that the local
      variation did not affect the concentration of elements in the sampling region.
      According to cluster analysis, 8 (As, Hg, Pb, Sb, Fe, Mn, Na and K) elements are
      indicative of important local pollution locations and their zone of impact in the
      region. By mapping the concentrations of eight indicative elements in lichen
      Xanthoria parietina of the Aegean region, it was possible to relate deposition to
      the existence of known sources of pollution in certain areas. Location of
      pollution sources such as iron-steel plants, and coal burning in the cities,
      industrial activity and two important coal-fired power plants generally
      corresponded with locations of highest element accumulations in the lichens.

PMID- 15262158
TI  - Evaluating river water quality through land use analysis and N budget approaches
      in livestock farming areas.
AB  - This study was carried out to evaluate the quality of river water by analysis of
      land use in drainage basins and by estimating the N budgets. The drainage basins
      of Shibetsu River (Shibetsu area) and Bekkanbeushi River (Akkeshi area) in
      eastern Hokkaido, Japan were selected for a case study, and the evaluation of
      water quality was up-scaled to the regional level in Hokkaido by using the
      Arcview/GIS and statistical information. Water sampling was carried out in August
      2001 and May 2002 in the Shibetsu and Akkeshi areas, respectively. The
      proportions of major land uses in drainage basins such as upland field, forest,
      urban area, wetland and wasteland for each sampling site were estimated by using
      topographic maps scaled at 1:25,000. The linear regression results showed that
      the correlation between NO3-N concentration and the proportion of upland in the
      drainage basins was highly and positively significant for both the Shibetsu area
      (r = 0.84, n = 57) and the Akkeshi area (r = 0.71, n = 73) at < 0.001
      significance level. The regression coefficients or impact factors of river water
      quality were 0.015 and 0.0052 for the Shibetsu and Akkeshi areas, respectively. A
      comparison of these results with that of the previous study results in Hokkaido
      indicated that the impact factors were highest for intensive livestock farming
      areas (0.040), medium for mixed agriculture and livestock farming (0.020-0.030),
      and the lowest for grassland-based dairy cattle and horse farming areas (0.0052
      0.015). The results of a simple regression analysis showed that the impact
      factors had a significant positive correlation with the cropland surplus N (r =
      0.93, P < 0.01), chemical fertilizer N (r = 0.82, P < 0.05), and manure
      fertilizer N (r = 0.76, P < 0.05), which were estimated by using the N budget
      approach. Using the best-correlated regression model, impact factors for all
      cities, towns and villages of the Hokkaido region were estimated. The NO3-N
      concentrations for all major rivers in Hokkaido were predicted by multiplying the
      estimated impact factors by the proportion of uplands. The regression analysis
      indicated that the predicted NO3-N concentrations were significantly correlated
      (r = 0.62, P < 0.001, n = 203) with the measured NO3-N concentrations, reported
      previously. It can be concluded that estimating the proportions of upland fields
      in drainage basins, and calculating cropland surplus N enables us to predict
      river water quality with respect to NO3-N concentration.

PMID- 15262159
TI  - Fungal spore source strength tester: laboratory evaluation of a new concept.
AB  - The airborne fungal spore concentration measured with air samplers during
      specific time intervals does not always adequately represent the maximum spore
      concentration levels, because of the sporadic nature of spore release. Hence, a
      reliable method is needed to directly assess the indoor fungal sources with
      respect to their spore aerosolization potential. In this study, the newly
      developed fungal spore source strength tester (FSSST), which aerosolizes spores
      from growth surfaces and samples the airborne fungi into a bioaerosol sampler,
      was evaluated in the laboratory. The FSSST's operational flow rates of 30 and
      12.5 l/min were tested. The fungal spores released from moldy surfaces were
      measured with an optical particle counter. Simultaneously, the spores were
      collected by a bioaerosol sampler: either with a 37-mm filter cassette or with
      the BioSampler. Three material types, ceiling tile, gypsum board and plastic
      sheet coated with agar, were tested after they were inoculated with the fungus
      Aspergillus versicolor. In addition, gypsum board naturally contaminated with
      various fungi (obtained from a mold-problem home) was tested in the laboratory
      using the FSSST. In all three laboratory-inoculated materials, the release rate
      of A. versicolor was found to be higher when the FSSST operated at 30 l/min than
      at 12.5 l/min. Nevertheless, even at 12.5 l/min the number of spores aerosolized
      from the source during 10 min was found sufficient to reflect the highest level
      of release that may occur in indoor environments. At 12.5 l/min, the release rate
      of A. versicolor during the first 10-min period was (23.9 +/- 17.7)x10(4) cm(-2)
      for ceiling tile, (1.3 +/- 0.3)x10(4) cm(-2) for gypsum board and (0.13 +/-
      0.08)x10(4) cm(-2) for agar surface (based on the samples collected with the
      BioSampler). The spore release rate was higher during the first 10 min than
      during the second 10 min of the FSSST application. It was observed that the
      particles aerosolized from the A. versicolor culture included spore aggregates
      and single spores, as well as mycelial fragments. Overall, 0.6 +/- 0.3% of spores
      detected on 1 cm2 of ceiling tile inoculated with A. versicolor were aerosolized
      during the 10-min source testing. The respective number was 9.2 +/- 1.0% for the
      laboratory-inoculated gypsum board, 0.002 +/- 0.001% for the laboratory
      inoculated plastic covered with agar and 1.8 +/- 0.2% for naturally contaminated
      gypsum board. Our data suggest that the FSSST provides very favorable conditions
      for the spore aerosolization and thus can be used in the field to assess the
      maximum potential spore release from a fungal source.

PMID- 15262160
TI  - Persistence of four s-triazine herbicides in river, sea and groundwater samples
      exposed to sunlight and darkness under laboratory conditions.
AB  - The persistence of terbuthylazine, simazine, atrazine and prometryn (s-triazine
      herbicides) was studied in sea, river and groundwaters during long-term
      laboratory incubation (127 days) under different laboratory conditions (light
      darkness at 20 degrees C). Analysis of herbicides was performed by GC-NPD and
      their identity was confirmed by GC-MSD. A micro on-line method for the isolation
      of herbicide residues was used. The results showed that light had little effect
      on the removal of the four herbicides in riverwater but had a marked effect on
      their removal from sea and groundwater. Surprisingly, this removal appeared to be
      inversely proportional to the concentration of dissolved organic materials. In
      general, the degradation order was similar in sea and riverwaters; simazine was
      the most readily degraded compound (t(1/2)= 29-49 days), while terbuthylazine was
      the most persistent with the longest half-lives (76-331 days). In groundwater,
      terbuthylazine also showed greater persistence but prometryn was the compound
      with a fastest degradation rate, half-lives ranged from 88 days for prometryn to
      approximately 100 days for the other three compounds in light conditions and 263
      366 days for prometryn and terbuthylazine, respectively, in darkness. Only for
      terbuthylazine was the remaining percentage at the end of the experiment higher
      than 50% under light conditions in riverwater, while in the other cases, the
      remaining percentage varied from 7 to 43% for simazine in seawater and atrazine
      in groundwater, respectively. Finally, a greater persistence was observed in
      groundwater for the four compounds.

PMID- 15262161
TI  - Persistence of pharmaceutical compounds and other organic wastewater contaminants
      in a conventional drinking-water-treatment plant.
AB  - In a study conducted by the US Geological Survey and the Centers for Disease
      Control and Prevention, 24 water samples were collected at selected locations
      within a drinking-water-treatment (DWT) facility and from the two streams that
      serve the facility to evaluate the potential for wastewater-related organic
      contaminants to survive a conventional treatment process and persist in potable
      water supplies. Stream-water samples as well as samples of raw, settled,
      filtered, and finished water were collected during low-flow conditions, when the
      discharge of effluent from upstream municipal sewage-treatment plants accounted
      for 37-67% of flow in stream 1 and 10-20% of flow in stream 2. Each sample was
      analyzed for 106 organic wastewater-related contaminants (OWCs) that represent a
      diverse group of extensively used chemicals. Forty OWCs were detected in one or
      more samples of stream water or raw-water supplies in the treatment plant; 34
      were detected in more than 10% of these samples. Several of these compounds also
      were frequently detected in samples of finished water; these compounds include
      selected prescription and non-prescription drugs and their metabolites, fragrance
      compounds, flame retardants and plasticizers, cosmetic compounds, and a solvent.
      The detection of these compounds suggests that they resist removal through
      conventional water-treatment processes. Other compounds that also were frequently
      detected in samples of stream water and raw-water supplies were not detected in
      samples of finished water; these include selected prescription and non
      prescription drugs and their metabolites, disinfectants, detergent metabolites,
      and plant and animal steroids. The non-detection of these compounds indicates
      that their concentrations are reduced to levels less than analytical detection
      limits or that they are transformed to degradates through conventional DWT
      processes. Concentrations of OWCs detected in finished water generally were low
      and did not exceed Federal drinking-water standards or lifetime health
      advisories, although such standards or advisories have not been established for
      most of these compounds. Also, at least 11 and as many as 17 OWCs were detected
      in samples of finished water. Drinking-water criteria currently are based on the
      toxicity of individual compounds and not combinations of compounds. Little is
      known about potential human-health effects associated with chronic exposure to
      trace levels of multiple OWCs through routes such as drinking water. The
      occurrence in drinking-water supplies of many of the OWCs analyzed for during
      this study is unregulated and most of these compounds have not been routinely
      monitored for in the Nation's source- or potable-water supplies. This study
      provides the first documentation that many of these compounds can survive
      conventional water-treatment processes and occur in potable-water supplies. It
      thereby provides information that can be used in setting research and regulatory
      priorities and in designing future monitoring programs. The results of this study
      also indicate that improvements in water-treatment processes may benefit from
      consideration of the response of OWCs and other trace organic contaminants to
      specific physical and chemical treatments.

PMID- 15262162
TI  - Impacts of runoff from sulfuric soils on sediment chemistry in an estuarine lake.
AB  - The impact of runoff from sulfuric soils in the heavily drained Cudgen Lake
      floodplain, eastern Australia on water quality and downstream coastal lake
      sediments has been examined. The oxidation of sulfidic soils and the
      transformation into sulfuric soils leads to changes not only in the upper soil
      profile but also affects drainage water quality and the chemistry of bottom
      sediments in receiving waters. Oxidation transforms the soil from a sink for
      sulfur and metals to a significant source for downstream environments. Sulfuric
      soils within the Cudgen Lake catchment contain 9.18 x 10(5) mol H+ per hectare as
      well as elevated concentration of metals (e.g. Al, Fe, Mn) and sulfate. These
      products of sulfidic soil oxidation are transported efficiently from the soil
      profile by the constructed drainage network and into the downstream lake system.
      The acid volatile sulfur (AVS), chromium reducible sulfur (CRS), total sulfur,
      organic carbon, and reactive iron contents present in the solid phase of the lake
      sediments are reported. The AVS/CRS, DOP and DOS values observed in the lake
      sediments show that natural monosulfide formation in the near surface sediments
      has been enhanced due to increased inputs of organic matter, sulfate, ferrous
      iron and other metals following development of the catchment. There are elevated
      concentrations of metals (e.g. As, Al, Cd, Cr, Hg, Zn and Pb) in the upper layer
      of monosulfidic lake sediments compared with the underlying pyritic sediments
      some of which exceed sediment quality guidelines. These metals could be released
      by dredging or through re-suspension during high flow conditions or enter the
      food chain.

PMID- 15262163
TI  - Biogeochemical behavior of organic carbon in the Trinity River downstream of a
      large reservoir lake in Texas, USA.
AB  - Dissolved and particulate organic carbon concentrations were measured and annual
      loads estimated for the Trinity River, the main freshwater input source to
      Galveston Bay, which lies on the upper Gulf coast of Texas, USA, during 2000
      2001. This river drains the forested lowlands south of a relatively large
      reservoir lake, Lake Livingston. A weak relationship between dissolved organic
      carbon (DOC) and Q(TR) indicated hydrologic control but separation of the data,
      based on individual discharge events, was necessary to improve interpretation.
      For instance, the first rain of the season resulted in only a modest increase in
      DOC concentrations and led to an inverse relationship with discharge, due to
      decreased lateral flow and increased infiltration of rainwater, with the lower
      flows being more efficient at DOC leaching from soils. In contrast, a long
      duration high discharge river crest event resulted in an opposite trend, i.e. a
      linear increase in DOC with increasing discharge rates. A short duration high
      discharge tropical storm showed reduced Trinity River DOC concentrations and the
      highest POC concentrations measured, likely resulting from the relatively short
      duration, and minimal contact time, of this event. In contrast to DOC, the
      concentrations of particulate organic carbon, POC (mg C l(-1)) were linearly
      correlated to suspended particulate matter (SPM) concentrations and accounted for
      between 10 and 12% of the total suspended load at low discharge but decreased to
      approximately 2% at high discharge. This suggests dilution by larger particles
      with a reduced organic carbon content, possibly silicate minerals, more readily
      resuspended at elevated levels of discharge. The annual total organic carbon
      (TOC) load to Galveston Bay, estimated from the slope of the daily load vs.
      discharge relationship, was 11.2 x 10(10) g C and calculated export coefficients
      (g C m(-2) year(-1)) were in good agreement with previous results. Using this
      relationship, accurate assessments of TOC flux inputs to Galveston Bay over the
      past quarter-century and in the future are possible by obtaining annual Trinity
      River discharge rates, which are readily available from the USGS. Comparing DOC
      riverine inputs to benthic sources in Trinity Bay, measured directly on the same
      day, indicates that the sediments contribute approximately 20% of total inputs of
      DOC to Trinity Bay. However, assuming a constant benthic source during low-flow
      conditions, which can occur for periods of up to 14 months in this region of
      Texas, benthic fluxes would account for > 80% of the total inputs into Trinity
      Bay. At high levels of discharge, the Trinity River discharges approximately 1.0
      x 10(9) g C day(-1) and dominates DOC inputs to Trinity Bay.

PMID- 15262164
TI  - Physico-chemical controls on phosphorus cycling in two lowland streams. Part 1 --
      the water column.
AB  - This paper investigates phosphorus (P) transport and transformation dynamics in
      two contrasting sub-catchments of the River Kennet, England. Samples were
      collected daily under baseflow and hourly under stormflow conditions using
      autosamplers for 2 years and analysed for a range of determinands (full P
      fractionation, suspended sediment (SS), cations, pH, alkalinity, temperature and
      oxygen). Concentrations of SRP, SUP, PP and SS were higher in the flashy River
      Enborne (means of 0.186, 0.071, 0.101 and 34 mg l(-1), respectively) than the
      groundwater-fed River Lambourn (0.079, 0.057, 0.028 and 9 mg l(-1),
      respectively). A seasonal trend in the daily P dataset was evident, with lower
      concentrations during intermediate flows and the spring (caused by a dilution
      effect and macrophyte uptake) than during baseflow conditions. However, in the
      hourly P dataset, highest concentrations were observed during storm events in the
      autumn and winter (reflecting higher scour with increased capacity to entrain
      particles). Storm events were more significant in contributing to the total P
      load in the River Enborne than the River Lambourn, especially during August to
      October, when dry antecedent conditions were observed in the catchment. Re
      suspension of P-rich sediment that accumulated within the channel during summer
      low flows might account for these observations. It is suggested that a P-calcite
      co-precipitation mechanism was operating during summer in the River Lambourn,
      while adsorption by metal oxyhydroxide groups was an important mechanism
      controlling P fractionation in the River Enborne. The influence of flow
      conditions and channel storage/release mechanisms on P dynamics in these two
      lowland rivers is assessed.

PMID- 15262165
TI  - Physico-chemical controls on phosphorus cycling in two lowland streams. Part 2-
      the sediment phase.
AB  - This article investigates the temporal and spatial controls on sediment
      phosphorus (P) dynamics in two contrasting sub-catchments of the River Kennet,
      England. Suspended sediment (collected under representative flow conditions) and
      size-fractionated bedload (collected weekly for one year) from the Rivers
      Lambourn and Enborne was analysed for a range of physico-chemical determinands.
      Total P concentrations were highest in the most mobile fractions of sediment:
      suspended sediment, fine silt and clay and organic matter (mean concentrations of
      1758, 1548 and 1440 microg P g(-1) dry sediment, respectively). Correlation
      analysis showed significant relationships between total P and total iron (n=
      110), total manganese (n= 110), organic matter (n= 110) and specific surface area
      (n= 28) in the Lambourn (r2 0.71, 0.68, 0.62 and 0.52, respectively) and between
      total P and total iron (n= 110), total manganese (n= 110) and organic matter (n=
      110) in the Enborne (r2 0.74, 0.85 and 0.68, respectively). These data highlight
      the importance of metal oxyhydroxide adsorption of P on fine particulates and
      organic matter. However, high total P concentrations in the granule gravel and
      coarse sand size fraction during the summer period (mean concentration 228 microg
      P g(-1) dry sediment) also highlight the role of calcite co-precipitation on P
      dynamics in the Lambourn. P to cation ratios in Lambourn sediment indicated that
      fine silt and clay and granule gravel and coarse sand size fractions were
      potential sources of P release to the water column during specific periods of the
      summer and autumn. In the Enborne, however, only the granule gravel and coarse
      sand size fraction had high ratios and a slow, constant release of P was
      observed. In addition, scanning electron microscopy work confirmed the
      association of P with calcite in the Lambourn and P with iron on clay particles
      in the Enborne. The study highlighted the importance of the chemical and physical
      properties of the sediment in influencing the mechanisms controlling P storage
      and release within river channels.

PMID- 15262166
TI  - Self-cleaning in an estuarine area formerly affected by 226Ra anthropogenic
      enhancements.
AB  - The estuary of the Odiel River has been affected by both direct discharges of
      phosphogypsum (radium enriched industrial waste) and dissolution and weathering
      of the exposed piles where this radium enriched waste was stored. In 1998 the
      waste management policy for industries changed. The direct discharges stopped and
      the new phosphogypsum piles were well protected against dissolution processes,
      avoiding any transference of radium into the environment. This work presents a
      study of the evolution with time (1999-2002) of the levels of 226Ra in river
      water and sediment samples with the new waste management policy. A liquid
      scintillation technique was used to measure the 226Ra activity concentration in
      sediment samples. A gas-proportional counter was also used to measure the 226Ra
      activity concentration in river water samples. The main conclusion is that a
      systematic and continuous decrease of the activity concentration of 226Ra with
      time in the Odiel River estuary is occurring. Thus, a possible self-cleaning in
      the estuary, once the direct waste discharges were avoided, can be inferred.

PMID- 15262167
TI  - Determination of solid-liquid partition coefficients (K(d)) for diazinon,
      propetamphos and cis-permethrin: implications for sheep dip disposal.
AB  - Two groups of chemicals are currently licensed for use in sheep dip products in
      the UK. These are organophosphate (OP) insecticides and synthetic pyrethroid (SP)
      insecticides. SPs are deemed to be less toxic to human health than OPs, although
      they are approximately 100 times more toxic to some elements of the aquatic
      environment. Three insecticides were selected for experimental investigation:
      diazinon, propetamphos (OPs) and cis-permethrin (SP), representative of the
      active ingredients used in sheep dip formulations, with additional uses in insect
      control in crops, and for domestic control of flies, mosquitoes, cockroaches,
      lice, ticks and spiders. The UK Government has recently reviewed agricultural
      practices relating to the disposal of used sheep dip, because the constituent
      insecticides are frequently detected in UK watercourses and the presence of these
      compounds is a severe hazard to the aquatic environment. Standard batch sorption
      experiments were carried out to investigate insecticide partitioning from water
      to soil, and the relationship between sorption and soil organic carbon content is
      discussed. Sorption isotherms and K(d) values showed that cis-permethrin
      adsorption was fastest on all five soils investigated, exhibiting the greatest
      total partitioning to the soil phase (83.8-94.8%) and high resistance to
      desorption. In comparison, the OP insecticides exhibited moderately strong soil
      adsorption as evidenced by their K(d) coefficients (diazinon K(d) 12-35 and
      propetamphos K(d) 9-60), with low sorption reversibility (< 15%). Calculation of
      a hydrological retardation factor in a scenario representative of a typical UK
      environment suggested that SP insecticides such as cis-permethrin will not
      migrate in the soil profile due to their virtual immobility and strong soil
      retention, and thus waste sheep dip disposal to agricultural land should not pose
      a risk to aquatic life if applied with appropriate controls.

PMID- 15262168
TI  - Dynamics of solutes and dissolved oxygen in shallow urban groundwater below a
      stormwater infiltration basin.
AB  - Artificial recharge of urban aquifers with stormwater has been used extensively
      in urban areas to dispose of stormwater and compensate for reduced groundwater
      recharge. However, stormwater-derived sediments accumulating in infiltration beds
      may act as a source of dissolved contaminants for groundwater. Concentrations of
      hydrocarbons, heavy metals, nutrients and dissolved oxygen (DO) were monitored at
      multiple depths in shallow groundwater below a stormwater infiltration basin
      retaining large amounts of contaminated organic sediments. Multilevel wells and
      multiparameter loggers were used to examine changes in groundwater chemistry
      occurring over small spatial and temporal scales. Rainfall events produced a
      plume of low-salinity stormwater in the first 2 m below the groundwater table,
      thereby generating steep vertical physico-chemical gradients that resorbed during
      dry weather. Heavy metals and hydrocarbons were below reference concentrations in
      groundwater and aquifer sediments, indicating that they remained adsorbed onto
      the bed sediments. However, mineralization of organic sediments was the most
      probable cause of elevated concentrations of phosphate and DOC in groundwater. DO
      supply in groundwater was severely limited by bed respiration which increased
      with temperature. Cold winter stormwater slightly re-oxygenated groundwater,
      whereas warm summer stormwater lowered DO concentrations in groundwater. Among
      several results provided by this study, it is recommended for management purposes
      that infiltration practices should minimize the contact between inflow stormwater
      and organic sediments retained in infiltration basins.

PMID- 15262169
TI  - Ionic charge, radius, and potential control root/soil concentration ratios of
      fifty cationic elements in the organic horizon of a beech (Fagus sylvatica)
      forest podzol.
AB  - The root/organic soil concentration ratio; R/S) of 50 cationic mineral elements
      was related to their ionic properties, including ionic radius (r), ionic charge
      (z), and ionic potential (z/r or z2/r). The materials studied were
      ectomycorrhizal beech (Fagus sylvatica L.) roots and their almost purely organic
      soil substrate, the O-horizon (mor; raw humus) of a Podzol in South Sweden,
      developed in a site which has been untouched by forestry or other mechanical
      disturbance since at least 50 years and located in an area with no local sources
      of pollution. Elements determined by ICP-AES were aluminium, barium, calcium,
      iron, potassium, magnesium, manganese, sodium and strontium. Determined by ICP-MS
      were silver, beryllium, bismuth, cadmium, cerium, cobalt, chromium, caesium,
      copper, dysprosium, erbium, europium, gallium, gadolinium, hafnium, mercury,
      holmium, indium, lanthanum, lithium, lutetium, niobium, neodymium, nickel, lead,
      praseodymium, rubidium, scandium, samarium, tin, terbium, thorium, titanium,
      thallium, thulium, uranium, vanadium, yttrium, ytterbium, zinc and zirconium. The
      R/S ratios were most clearly related to the ionic potential of the cationic
      elements studied, which accounted for approximately 60% of the variability in R/S
      among elements. The ionic charge of an element was more important than the ionic
      radius. Elements with high ionic charge had low R/S ratios and vice versa. No
      clear differences in R/S between essential and non-essential plant nutrients were
      observed, especially when ions of similar charge were compared.

PMID- 15262170
TI  - Estimating the biogenic emissions of non-methane volatile organic compounds from
      the North Western Mediterranean vegetation of Catalonia, Spain.
AB  - An estimation of the magnitude of non-methane volatile organic compounds (NMVOCs)
      emitted by vegetation in Catalonia (NE of the Iberian Peninsula, Spain), in
      addition to their superficial and temporal distribution, is presented for policy
      and scientific (photochemical modelling) purposes. It was developed for the year
      2000, for different time resolutions (hourly, daily, monthly and annual) and
      using a high-resolution land-use map (1-km2 squared cells). Several
      meteorological surface stations provided air temperature and solar radiation
      data. An adjusted mathematical emission model taking account of Catalonia's
      conditions was built into a geographic information system (GIS) software. This
      estimation uses the latest information, mainly relating to: (1) emission factors;
      (2) better knowledge of the composition of Catalonia's forest cover; and (3)
      better knowledge of the particular emission behaviour of some Mediterranean
      vegetal species. Results depict an annual cycle with increasing values in the
      March-April period with the highest emissions in July-August, followed by a
      decrease in October-November. Annual biogenic NMVOCs emissions reach 46.9 kt,
      with monoterpenes the most abundant species (24.7 kt), followed by other biogenic
      volatile organic compounds (e.g. alcohols, aldehydes and acetone) (16.3 kt), and
      isoprene (5.9 kt). These compounds signify 52%, 35% and 13%, respectively, of
      total emission estimates. Peak hourly total emission for a winter day could be
      less than 10% of the corresponding value for a summer day.

PMID- 15262171
TI  - Use of sorption and extraction tests to predict the dynamics of the interaction
      of trace elements in agricultural soils contaminated by a mine tailing accident.
AB  - Over 2000 ha of agricultural soils were contaminated by a pyritic sludge and
      acidic waste waters coming from a spill from a mining exploitation. The affected
      soils were acidic with sandy-loam texture (SL), loamy with neutral pH (L), and
      calcareous, saline, with clay texture (Cs). The Cs soils were contaminated only
      with acidic waste waters. Sorption and extraction tests were applied to examine
      the medium-term dynamics of the interaction of trace elements (As, Cd, Cu, Pb and
      Zn) in the soils. The solid-soil solution distribution coefficient (KD) was
      determined in soil samples taken 3 months (initial stage, 3M samples) and then
      nearly 2 years (final stage, 21M samples) after the accident. Distribution
      coefficient values ranged from the lowest values in the SL samples (from 0.2 l
      kg(-1) for Cd and Zn to 25 l kg(-1) for As) to higher values in the L and Cs
      soils. Lead and As had the highest KD in all soils (over 10(5) l kg(-1) in the L
      soils). No clear dynamics pattern could be derived from these data because of the
      low heavy metal concentrations in the soil solution. As a complementary approach,
      four single extractions (0.01 and 1 mol l(-1) CaCl2; 0.05 mol l(-1) EDTA; 0.43
      mol l(-1) CH3COOH) were applied to soil and sludge samples. Samples derived from
      submitting field 3M samples to drying-wetting (DW) cycles were included to define
      a complete laboratory approach to predict field dynamics. Results from extraction
      tests indicated that changes of the trace element interaction over time depended
      on the soil pH and on the source of contamination. For those soils affected only
      by the acidic waste waters, where an increase in fixation occurred, natural
      processes such as diffusion controlled dynamics. For those soils contaminated by
      a mixed source, the dynamics of the interaction was the resultant process of the
      combination of the natural attenuation and the oxidation of the pyritic sludge.
      This latter process led to an increase in the remobilization for those elements
      associated with soluble secondary minerals (Cd and Zn) and to an increase in the
      fixation for those elements coprecipitating with insoluble secondary minerals (Pb
      and As). Drying-wetting cycles were useful to predict the dynamics in the field
      at month-year scale. The CH3COOH was recommended as the best test among those
      studied here to derive conclusions about dynamics pattern because it provided
      significant desorption yields in most scenarios. Acidic soils with sludge
      contamination represented the scenarios with the highest risk, while calcareous
      soils better attenuated contamination. In a longer time scale, the depletion of
      calcareous components needs to be controlled.

PMID- 15262172
TI  - Population dose in the vicinity of old Spanish uranium mines.
AB  - Regional surveys were conducted to determine exposure to natural sources of
      radiation for people in the vicinity of old Spanish uranium mines. The surveys
      evaluated indoor radon concentrations and outdoor and indoor external gamma dose
      rates. Indoor radon concentrations were measured in 222 dwellings by means of
      nuclear track-etched detectors. The terrestrial gamma ray dose rate was measured
      outdoors and indoors at a total of 256 points and 115 points, respectively.
      Estimates mean annual effective doses for the six areas studied ranged from 3.2
      to 5.1 mSv per year, which is between 1.2 and 2 times higher than the average
      national value.

PMID- 15262173
TI  - Organochlorine compounds in breast-fed vs. bottle-fed infants: preliminary
      results at six weeks of age.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and 1,1,1
      trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous compounds with
      carcinogenic and teratogenic properties. They are chemically very stable and
      lipophilic and, therefore, accumulate in our food-chain. They are prenatally
      transmitted from mother to foetus, and mother's milk due to its high lipid
      content is an elimination pathway of special importance. Therefore, breast
      feeding has been held responsible for elevated concentrations of these
      organochlorine compounds as well as for harmful effects in children later in
      life. METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and
      bottle-fed infants at 6 weeks of age. Blood specimens were immediately
      centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis.
      Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, and
      the organic metabolite of DDT, p,p << -DDE, were analysed with capillary gas
      chromatography with electron capture detection. Reliability was tested with gas
      chromatography-mass spectrometry. RESULTS: There were no differences between the
      study groups of breast-fed and bottle-fed infants with regard to sex
      distribution, gestational age, birth-weight, age of the mothers, and smoking
      behaviour of the parents. In contrast, serum concentrations of all organochlorine
      compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed
      infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l;
      PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 vs.
      0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breast-feeding
      significantly increases the pollution of our infants with different
      organochlorine compounds as early as at 6 weeks of age. The progress of the
      present study will show whether this pollution will further increase with longer
      duration of breast-feeding, and whether breast-feeding bears any health risks for
      our offspring.

PMID- 15262174
TI  - Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?
AB  - Complications of pregnancy, particularly pre-eclampsia (PET) and intra-uterine
      growth restriction (IUGR) have been associated with future maternal
      cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance,
      widespread endothelial damage and dysfunction, coagulation defects and increased
      systemic inflammatory response, shares many risk factors with CVD. This review
      describes the pathology of PET and the maternal metabolic response and discusses
      the possible underlying mechanisms common to CVD and PET. The contributions of
      pre-existing risk factors and of the exaggerated atherogenic-like response seen
      in PET persisting post-partum to future CVD are considered. The potential for
      interventions based on early assessment of cardiovascular risk is addressed. We
      conclude that despite the low immediate cardiovascular risk in a population of
      young women, a pregnancy with multiple complications including PET, premature
      delivery and IUGR, carries a seven-fold additive risk of future disease. These
      women may be an appropriate cohort for CVD risk screening and for possible
      intervention.

PMID- 15262175
TI  - Endothelin-1(1-31) levels are increased in atherosclerotic lesions of the
      thoracic aorta of hypercholesterolemic hamsters.
AB  - OBJECTIVE: The novel vaso-constricting 31-amino acid-length endothelin-1 [ET-1(1
      31)] is selectively produced by human mast cell chymase via its action on big ET
      1. However, the pathological role of ET-1(1-31) in atherosclerosis remains
      unclear. The aim of this study was to clarify vasoconstrictive response and
      expression of ET-1(1-31) in atherosclerotic aorta. METHODS AND RESULTS: Syrian
      golden hamster, was used for preparing the atherosclerotic models by the
      administration of a high cholesterol diet (HC), treatment with the nitric oxide
      synthase inhibitor (Nomega-nitro-L-arginine methylester, L-NAME) alone, or both
      (HC and L-NAME) for 40 weeks. Early atherosclerosis was observed in the case of
      HC or L-NAME alone treatments respectively and severe atherosclerosis was
      observed in the case of combined HC and L-NAME treatment. Vasoconstriction
      induced by ET-1(1-31) was not altered by the atherosclerotic changes, but the
      expression pattern of ET-1(1-31) was different at each stage of the
      atherosclerotic aorta. ET-1(1-31) was observed rarely in normal aortas or in
      early atherosclerotic lesions, but ET-1(1-31) expression was dramatically
      increased in aortic neointima and adventitia in a state of atherosclerosis with
      severe inflammation. CONCLUSION: ET-1(1-31) might play in a role of promoting
      atherosclerosis, and especially be involved in inflammatory mediation during the
      progression of atherosclerosis.

PMID- 15262176
TI  - RRR-alpha-tocopherol decreases the expression of the major scavenger receptor,
      CD36, in human macrophages via inhibition of tyrosine kinase (Tyk2).
AB  - The class B scavenger receptor, CD36, binds to oxidized LDL (OxLDL), is present
      in atherosclerotic lesions, and is upregulated by OxLDL or AcLDL. Previously we
      have shown that RRR-alpha-tocopherol (AT) enrichment of human monocyte-derived
      macrophages inhibited OxLDL or AcLDL induced CD36 expression. The mechanism by
      which AT inhibited CD36 expression is not known. In the present study, we
      explored the mechanism by which AT decreases CD36 expression in human
      macrophages. Macrophages were enriched with AT (100 microM) or N-acetyl cysteine
      (NAC, 6 mM) overnight and then incubated with oxLDL or AcLDL for 48 h. The effect
      of protein kinase C inhibitors, and tyrosine kinase inhibitors on OxLDL or AcLDL
      induced CD36 expression was quantitated by flow cytometry. Protein kinase C
      inhibitors or NAC had no effect while there was a significant inhibition with
      tyrosine kinase inhibitors (P < 0.01). OxLDL or AcLDL significantly increased
      tyrosine kinase activity which was significantly inhibited by pre-incubation with
      AT or with tyrosine kinase inhibitors. Western blotting revealed an increase in
      Tyk2 as well as phosphotyk2 with OxLDL or AcLDL. Immunoprecipitation of CD36
      followed by Western blotting with Tyk2 antibodies revealed that Tyk2 was
      associated with CD36. In conclusion, this study demonstrates an additional direct
      cellular effect of AT, i.e. inhibition of CD36 expression via inhibition of
      tyrosine kinase (Tyk2).

PMID- 15262177
TI  - Modified atherogenic lipoproteins induce expression of pentraxin-3 by human
      vascular smooth muscle cells.
AB  - Inflammation is a critical contributing factor to the development and the
      progression of atherosclerosis. Recently, the acute-phase protein pentraxin-3
      (PTX3), which has C-terminal sequence homology with the classic pentraxin C
      reactive protein (CRP), was described to be increased in patients with myocardial
      infarction. In this study, we have investigated the capacity of human primary
      vascular smooth muscle cells (VSMC), derived from arterial specimens of ten
      different patients, to express PTX3 after incubation with atherogenic
      lipoproteins. Enzymatically degraded LDL (E-LDL), which is present in human early
      lesions, mediated a rapid cholesterol loading and foam cell transformation of
      primary VSMC, which was paralleled by a marked dose- and time-dependent
      expression of PTX3 mRNA and release of the acute-phase protein. Expression of
      PTX3 mRNA was delayed and remained almost undetectable for up to 6 h of
      incubation with E-LDL. However, during extended exposure to E-LDL for more than
      24 h, PTX3 mRNA expression increased by more than 15-fold in VSMC foam cells,
      which was reflected by a concomitant release of up to 211 ng/ml PTX3 protein. We
      provide evidence for marked expression of PTX3 by VSMC induced by degraded
      lipoproteins, which may lead to an in situ vascular acute-phase reaction,
      contributing to the inflammatory pathogenesis of atherosclerosis.

PMID- 15262178
TI  - Zinc reduces intimal hyperplasia in the rat carotid injury model.
AB  - BACKGROUND: The response to arterial injury following balloon dilatation is known
      to involve proliferative and inflammatory processes. The current widespread use
      of stents to maintain arterial patency not only does not eliminate but possibly
      exaggerates the proliferative and inflammatory phenotype and although drug
      eluting stents are available, their long-term safety is yet to be determined.
      Zinc is a trace element that serves as a cofactor of many enzymes. Interestingly,
      it has been shown to have anti-inflammatory and anti-proliferative properties. We
      thus sought to investigate its effect on smooth muscle cell proliferation and
      intimal thickening in the rat carotid artery injury model. METHODS AND RESULTS:
      Smooth muscle cells (SMC) were cultured from carotid arteries of rats and
      proliferation was assessed by thymidine incorporation after exposure to different
      concentrations of zinc. Next, carotid artery injury was induced in rats by
      balloon dilatation and they were either treated with I.P injections of zinc or
      PBS for 2 weeks until sacrifice for assessment of neointimal formation and lumen
      area. Zinc inhibited in vitro SMC proliferation in a dose-dependent manner. In
      vivo, zinc treatment resulted in a 50% reduction in neointimal area and a
      significant decrease in neointimal/media ratio with no significant change in
      lumen area. CONCLUSION: Thus, zinc appears to reduce neointimal growth and should
      be tested by local delivery systems including stent coatings.

PMID- 15262179
TI  - Simvastatin suppresses coronary artery endothelial tube formation by disrupting
      Ras/Raf/ERK signaling.
AB  - Since we recently demonstrated that high-density lipoprotein induced human
      coronary artery endothelial cell (HCEC) tube formation through Ras/Raf/ERK
      (extracellular-signal-regulated kinase) activation [Arterioscler. Thromb. Vasc.
      Biol. 23 (2003) 802], it is possible that lipid-lowering agents such as statins,
      which reduce the prenylation of Ras, could decrease such tube formation.
      Therefore, we investigated whether this event occurs through inhibition of the
      Ras/Raf/ERK pathway. We developed an in vitro model of EC tube formation on a
      matrix gel. Simvastatin inhibited serum-induced endothelial tube formation after
      18 h. The inhibition of ERK activity suppressed serum-induced tube formation.
      Farnesylpyrophosphate (Fpp), which translocates Ras from the cytoplasm to the
      cell membrane, rescued this inhibition. In addition, farnesyltransferase I
      inhibitor, which inhibits Ras farnesylation, and dominant-negative Ras (N17) also
      inhibited serum-induced tube formation. Although Fpp activated Ras assessed by a
      Ras pull-down assay and phospho(p)-ERK1/2, Fpp-induced p-ERK1/2 activation was
      not inhibited by simvastatin. In conclusion, simvastatin-induced Ras/Raf/ERK
      inactivation is a potent signal in the anti-angiogenic phenotype of HCECs. Fpp
      counteracted simvastatin-induced Ras/Raf/ERK inactivation.

PMID- 15262180
TI  - Possible involvement of p44/p42 MAP kinase in retinoic acid-stimulated vascular
      endothelial growth factor release in aortic smooth muscle cells.
AB  - Retinoic acid modulates cell growth and differentiation of the vascular system.
      Vascular endothelial growth factor (VEGF) is known as a vascular permeability
      factor and a potent mitogen for vascular endothelial cells. In the present study,
      we investigated whether retinoic acid induces VEGF release in aortic smooth
      muscle A10 cells and if so, the mechanism of VEGF release. Retinoic acid
      stimulated VEGF release dose-dependently over the range 0.1 nM-0.1 microM. The
      retinoic acid-stimulated VEGF release was significantly reduced by actinomycin D.
      Retinoic acid induced the phosphorylation of p44/p42 mitogen-activated protein
      (MAP) kinase but not p38 MAP kinase or stress-activated protein kinase/c-Jun N
      terminal kinase among the MAP kinase superfamily. This effect of retinoic acid
      was dose-dependent (30 nM-5 microM) and the maximum effect was observed at 0.3
      microM. The retinoic acid-stimulated release of VEGF was significantly reduced by
      PD98059 and U0126, specific MEK inhibitors, which attenuated the retinoic acid
      induced phosphorylation of p44/p42 MAP kinase. These results strongly suggest
      that retinoic acid stimulates the release of VEGF in a p44/p42 MAP kinase
      dependent manner in aortic smooth muscle cells.

PMID- 15262181
TI  - Lack of direct effect of moderate hyperleptinemia to improve endothelial function
      in lean rat aorta: role of calorie restriction.
AB  - Leptin stimulates vascular sympathetic activity and NO release. The resulting
      effect of hyperleptinemia on endothelial function is unknown. Reduction of food
      intake associated with hyperleptinemia may mediate some of the vascular effects
      of leptin. This study was designed to assess the relative effects of short-term
      moderate caloric restriction and hyperleptinemia on vascular function in lean
      rat. Endothelium-dependent and -independent vasorelaxation, nitric oxide synthase
      (eNOS) expression and nitrite production were measured in lean rats receiving
      leptin subcutaneous infusion (-26% caloric intake, -4% body weight versus
      control) or moderate caloric restriction (pair-feeding) for one week. Plasma
      leptin was increased (P < = 0.05) by approximately 300% in the leptin-infused
      group, while it decreased (P < or = 0.05) by approximately 40% in calorie
      restricted animals. Both leptin infusion and calorie restriction resulted in
      improved (P < 0.05) endothelium-dependent vasorelaxation to acetylcholine (EC50: 
      6.1 +/- 0.2 and -6.2 +/- 0.2 versus -5.4 +/- 0.2 in control) and unaltered
      endothelium-independent vasodilation to DEA-NONOate. Furthermore, in aortas from
      leptin-infused and calorie-restricted rats, expression of eNOS and nitrite
      production were increased (P < = 0.05) to similar extent compared to control
      animals. These findings suggest that moderate short-term calorie restriction with
      adaptive hypoleptinemia has independent beneficial effects on endothelial
      function in lean animals by enhancing eNOS expression and function. In addition,
      physiological hyperleptinemia does not independently contribute to improved
      vascular function above and beyond the effect of calorie restriction.

PMID- 15262182
TI  - Induction of connective tissue growth factor (CTGF) in human endothelial cells by
      lysophosphatidic acid, sphingosine-1-phosphate, and platelets.
AB  - Endothelial dysfunction is characterized by multiple interactions between
      endothelial cells and components of the blood. This study focussed on the
      induction of the pro-atherogenic connective tissue growth factor (CTGF) in
      endothelial cells by bioactive lipids and platelets. Lysophosphatidic acid (LPA)
      and sphingosine-1-phosphate (S1P) led to a time- and concentration-dependent
      increase in CTGF mRNA and protein expression in the human endothelial cell line
      EAHY 926 and in primary cultures of human umbilical vein endothelial cells
      (HUVEC). As both cell types expressed various receptors for LPA and S1P,
      signaling pathways were further characterized by pharmacological means: induction
      of CTGF was pertussis toxin-insensitive and inhibition of activation of p42/44
      MAP kinases only partially reduced CTGF expression. On the contrary, interference
      with the RhoA signaling pathway by simvastatin, an inhibitor of
      geranylgeranyltransferases, or the Rho-kinase inhibitor Y27632 prevented
      induction of CTGF. Co-incubation of endothelial cells with freshly isolated human
      platelets significantly increased the expression of CTGF mRNA in endothelial
      cells, which was also sensitive to simvastatin. Up-regulation of CTGF in
      endothelial cells, induced by LPA, S1P, or platelets, may contribute to the
      initiation and progression of atherosclerosis. Interference of simvastatin with
      the synthesis of this pro-atherogenic factor further supports the anti
      atherogenic role of statins.

PMID- 15262183
TI  - Screening for functional sequence variations and mutations in ABCA1.
AB  - Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible
      for the genetic HDL-deficiency syndromes, which are characterized by severely
      diminished plasma HDL-C levels and a predisposition to cardiovascular disease and
      splenomegaly. The ABCA1 gene contains 50 exons and codes for a 2261-amino acid
      long membrane protein that facilitates phospholipid and cholesterol transport.
      Several mutations have been identified so far as responsible either for Tangier
      disease or for reduced HDL levels. We have selectively looked for additional
      polymorphisms in functionally relevant regions of the gene in cohorts constituted
      of individuals with altered HDL levels as well as healthy blood donors and
      octogenarians, and screened for mutations in the complete coding region of
      selected individuals with extremely aberrant HDL levels. In the promoter region,
      which is important for regulation of gene expression, we have identified several
      polymorphisms including one VNTR polymorphism, located at a putative ZNF202
      binding site, which displayed different binding of ZNF202 in an electromobility
      shift assay. Three novel SNPs were discovered in the promoter region (G1047C,
      C1152T and C1440T). The prevalence of exchange G1047C (G-395C) was found
      significantly increased in probands with low HDL compared to probands with high
      HDL. Exchanges C1152T (C-290T) and C1440T (C-7T) were significantly more frequent
      in the cohort with low HDL compared to healthy blood donors and octogenarians. In
      the C-terminal part of ABCA1, known to interact with other proteins, two novel
      sequence variations (F2163S and V2244I) have been found in one phenotype related
      to cardiovascular disease, but none in the aforementioned cohorts. In one
      individual with extremely high HDL levels, the V771M polymorphism was found in a
      homozygous state. In patients with HDL deficiency, three novel mutations have
      been identified (W590L, W840R and R1068C). To facilitate further research in
      ABCA1 sequence variations and expand our understanding of their effects, we are
      introducing a webpage archive (http://www.abca1-mutants.all.at) containing all
      sequence variations reported in ABCA1 so far. This webpage provides a more recent
      and detailed summary of sequence variations and mutations in ABCA1 than existing
      databases and should also be of interest for molecular diagnosis of ABCA1-related
      HDL deficiency.

PMID- 15262184
TI  - Association of a 5178C-->A (Leu237Met) polymorphism in the mitochondrial DNA with
      a low prevalence of myocardial infarction in Japanese individuals.
AB  - Because mitochondria are the major sources of reactive oxygen species (ROS) in
      cells, certain alterations in mitochondrial functions can lead to metabolic
      perturbation in vascular endothelial cells and smooth muscle cells, resulting in
      vascular dysfunction. We previously demonstrated that a C --> A transversion in
      mitochondrial DNA (mtDNA) at nucleotide 5178 of the NADH dehydrogenase subunit 2
      (ND2) gene, which results in a Lue --> Met substitution at amino acid 237, was
      found more frequently in Japanese centenarians than in controls. We also
      demonstrated that this Mt5178C --> A polymorphism has anti-atherosclerotic
      effects in diabetic subjects. We have now examined whether the Mt5178C --> A
      (Leu237Met) polymorphism in the mitochondrial ND2 gene is associated with a low
      prevalence of myocardial infarction (MI) in a case-control study. The genotype of
      ND2 gene was determined either with a polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) or a colorimetry-based allele-specific
      DNA probe assay. Multivariate logistic regression analysis with adjustment for
      age, gender, body mass index, smoking status, hypertension, diabetes mellitus,
      hypercholesterolemia, and hyperuricemia revealed that the frequency of the
      Mt5178A genotype was significantly higher in controls than in subjects with MI.
      These results suggest that the 5178A genotype of mitochondrial ND2 gene
      polymorphism is protective against MI; and this effect would explain, at least in
      part, its contribution to longevity.

PMID- 15262185
TI  - Interactions between common genetic polymorphisms in ABCG5/G8 and CYP7A1 on LDL
      cholesterol-lowering response to atorvastatin.
AB  - Cholesterol excretion by ATP binding cassette transporters G5 and G8 (ABCG5/G8)
      and bile acid biosynthesis by cholesterol 7alpha-hydroxylase (CYP7A1) are major
      pathways for the removal of cholesterol into bile. To investigate the
      interactions between common polymorphisms in ABCG5/G8 and CYP7A1 and statin
      response, we examined the relationships between five non-synonymous polymorphisms
      in ABCG5/G8 (Q604E, D19H, Y54C, T400K, and A632V) and a promoter variant in
      CYP7A1 (A-204C) in 337 hypercholesterolemic patients treated with atorvastatin
      10mg. The ABCG8 H19 allele was significantly associated with a greater LDL
      cholesterol reduction relative to the wild type D19 allele (39.6% versus 36.6%, P
      = 0.043). This difference was enhanced in non-carriers of the CYP7A1 promoter
      polymorphism (42.7% versus 38.2%, P = 0.048), and was diminished in accordance
      with the number of CYP7A1 variant alleles (1.8% in heterozygotes and 0.2% in
      homozygotes). Combination analysis of these polymorphisms explained a greater
      percentage of LDL cholesterol response variation (8.5% difference across
      subgroups) than did single polymorphism analysis (4.2% in CYP7A1 and 3.0% in
      ABCG8 D19H). The other ABCG5/G8 polymorphisms did not show any significant
      interactions with the CYP7A1 polymorphism. We conclude that the ABCG8 H19 and
      CYP7A1 C-204 alleles appear to interact in a dose-dependent manner on
      atorvastatin response.

PMID- 15262186
TI  - Cardiovascular risk profiles in UK-born Caribbeans and Irish living in England
      and Wales.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality among
      Caribbean and Irish origin people living in England and Wales. Yet mortality from
      coronary heart disease (CHD) of migrant Caribbeans is lower than the national
      average, while stroke mortality is higher. The Irish experience higher than
      average mortality from both diseases. Little is known about the health of the
      children of these migrants. The Health Survey for England (HSE) 1999 was used to
      investigate for the first time cardiovascular risk factors in UK-born Caribbeans
      aged 35-44 and Irish aged 35-44 and 45-54 years. Caribbean men were more likely
      to smoke but had higher mean HDL-cholesterol than men in the general population.
      Caribbean women had greater body mass indices and lower mean triglyceride levels.
      Irish men in both age groups smoked more than men in the general population, but
      in the younger group had lower diastolic blood pressure (BP). At age 35-44 only,
      Irish women were shorter than women in the general population. These findings
      were independent of differences in socio-economic position. Previously, Caribbean
      born migrants to Britain had generally favourable lipid profiles in line with
      lower CHD rates, despite obesity and diabetes. The nationally representative but
      small-scale data presented here suggest that UK-born Caribbeans appear to be
      losing this more favourable lipid pattern and among men smoking rates are now
      higher compared with general population men, suggesting that an increase in CHD
      rates can be expected. Further research should examine how improved education and
      specific intervention programs could be used to reduce smoking among UK-born
      Irish and Caribbean men, and obesity among UK-born Caribbean women. The next HSE
      also needs to include adequate numbers of younger people of different ethnic
      origins to allow time trends in these anthropometric, behavioural and metabolic
      risk factors to be examined reliably and fully.

PMID- 15262187
TI  - Simvastatin inhibits lymphocyte function in normal subjects and patients with
      cardiovascular disease.
AB  - HMG-CoA reductase inhibitors (statins) block the mevalonate pathway, preventing
      biosynthesis of cholesterol and isoprenoids. We investigated the effect of
      simvastatin on lymphocytes from normal human subjects and cardiovascular disease
      patients in order to provide a model for the in vivo actions of statins. Thirteen
      healthy volunteers were treated with 40 mg per day of simvastatin following which
      mean total cholesterol was reduced by 23% (S.D.+/- 11.7%) and mean LDL
      cholesterol by 36% (S.D.+/- 16.3%). Lymphocyte lipid raft levels, represented by
      Lyn and Fyn, were also reduced by simvastatin. Treatment with simvastatin did not
      alter ex vivo T-lymphocyte proliferation. However, the in vitro addition of 1
      microM simvastatin reduced T-lymphocyte proliferation by 39% (S.D.+/- 18.1%) and
      a combination of prenyl transferase inhibitors reduced proliferation by 19%
      (S.D.+/- 22.7%). We also assessed the cytotoxicity of natural killer (NK) cells-a
      T-lymphocyte subset. NK cell cytotoxicity ex vivo was reduced by 30% (S.D.+/-
      33.6%) following oral simvastatin treatment and by 56% (S.D.+/- 24.68%) after the
      in vitro addition of 1 microM simvastatin. Significant ex vivo reductions in T
      cell proliferation and NK cell cytotoxicity were observed in patients with
      cardiovascular disease on treatment with statins. NK cells have been implicated
      in the pathogenesis of atherosclerosis, so the effect of statin therapy on NK
      cell cytotoxicity may contribute to the benefits of statins in cardiovascular
      disease.

PMID- 15262188
TI  - Homocysteine and carotid atherosclerosis in chronic renal failure--the
      confounding effect of renal function.
AB  - Since total homocysteine (tHcy) level is markedly elevated in patients with
      chronic renal failure (CRF), it has been presented as a potential factor
      contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was
      to examine the significance of elevated tHcy level and other cardiovascular risk
      factors for carotid atherosclerosis in patients with CRF. In this cross-sectional
      study, 135 study patients with CRF (52 +/- 11 years) included 58 patients with
      moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant
      recipients. In addition, 58 control subjects were examined. The association of
      tHcy level and classic risk factors for atherosclerosis with common carotid
      artery intima-media thickness (IMT) or carotid artery plaque score was examined.
      We found no association between tHcy and carotid IMT or a high carotid plaque
      score in the CRF patient groups. No consistent association was found between
      elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral
      arterial disease. Renal function, described as creatinine clearance, was the
      strongest determinant for tHcy level. Significant predictors of carotid
      atherosclerosis were age, duration of hypertension and elevated low-density
      lipoprotein cholesterol level. In conclusion, the present study shows no apparent
      association between tHcy level and atheromatous carotid findings in patients with
      CRF. However, because of the changing renal function in the course of renal
      disease, the strong confounding effect of renal function may not be adequately
      controlled for the analysis of the significance of elevated tHcy level for CVD in
      patients with CRF.

PMID- 15262189
TI  - Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase
      activity in vivo.
AB  - A major factor contributing to cardiovascular mortality in type 2 diabetes is
      dyslipidemia, characterized by low HDL cholesterol and high triglycerides, rather
      than elevated LDL cholesterol. Lipoprotein lipase (LPL) is the rate-limiting
      enzyme of triglyceride removal from plasma and has been implicated in
      atherosclerosis. Since treatment with statins significantly reduces
      cardiovascular morbidity in diabetes, we analyzed the lipid profile and LPL
      activities in 61 patients with type 2 diabetes before and 8 weeks after
      initiation of atorvastatin (40 mg) or placebo treatment. Lipid parameters and LPL
      activity were unchanged under treatment with placebo. Atorvastatin treatment
      resulted in a 30% reduction of total and a 45% reduction of LDL cholesterol (6.06
      +/- 1.39 mmol/L versus 4.14 +/- 1.27 mmol/L and 4.11 +/- 1.13 mmol/L versus 2.27
      +/- 0.89 mmol/L, both P < 0.0001). Triglycerides and VLDL cholesterol were also
      significantly reduced by statin therapy (2.24 +/- 2.11 mmol/L versus 1.82 +/-
      1.46 mmol/L and 1.08 +/- 1.56 mmol/L versus 0.67 +/- 0.66 mmol/L, both P < 0.05).
      HDL cholesterol was not different between the atorvastatin and the placebo group.
      Compared to baseline, LPL activity was increased by 25% after atorvastatin
      treatment (213.0 +/- 28.1 nmol/mL/min versus 171.9 +/- 17.7 nmol/mL/min, P <
      0.01). Our data demonstrate that atorvastatin induces a significant improvement
      of diabetic dyslipidemia and a significant increase of LPL activity. Since low
      LPL activity indicates an increased cardiovascular risk, the statin-mediated
      increase in LPL activity may help to explain the reduction of CAD in diabetic
      patients treated with statins.

PMID- 15262190
TI  - Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on the
      oxidizability and thrombogenicity of low-density lipoprotein.
AB  - Consumption of oily fish and fish oils is associated with protection against
      cardiovascular disease. Paradoxically, long-chain polyunsaturated fatty acids
      present in low-density lipoprotein (LDL) are suggested to be susceptible to
      oxidation. It is not clear whether eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have similar effects on the susceptibility of LDL to
      oxidation or whether they affect the thrombogenicity of oxidized LDL. This study
      examined the influence of highly purified preparations of EPA and DHA on LDL
      oxidizability and LDL-supported thrombin generation in healthy human volunteers.
      Forty-two healthy volunteers were randomly assigned to receive olive oil
      (placebo), an EPA-rich oil or a DHA-rich oil for 4 weeks at a dose of 9 g
      oil/day. EPA and DHA were incorporated into LDL phospholipids and cholesteryl
      esters during the supplementation period, but were progressively lost during ex
      vivo copper-mediated oxidation. Following supplementation, the EPA treatment
      significantly increased the formation of conjugated dienes during LDL oxidation
      compared with baseline, whereas the DHA treatment had no effect. Neither
      treatment significantly affected the lag time for oxidation, oxidation rate
      during the propagation phase or maximum diene production. Neither EPA nor DHA
      significantly affected the thrombotic tendency of oxidized LDL compared with the
      placebo, although DHA tended to decrease it. In conclusion, there are subtle
      differences in the effects of EPA and DHA on the oxidizability and
      thrombogenicity of LDL. DHA does not appear to increase the susceptibility of LDL
      to oxidation to the same degree as EPA and has a tendency to decrease LDL
      supported thrombin generation.

PMID- 15262191
TI  - Prothrombotic markers in familial combined hyperlipidemia: evidence of
      endothelial cell activation and relation to metabolic syndrome.
AB  - BACKGROUND: Familial combined hyperlipidemia (FCHL) is characterized by a varied
      expression of hypertriglyceridemia and hypercholesterolemia within a family, and
      a high risk of premature coronary artery disease. The present study evaluated a
      number of potential prothrombotic markers in familial combined hyperlipidemia,
      and studied their relationship to the hypercholesterolemic (Fredrickson type IIa)
      and hypertriglyceridemic (IIb and IV) phenotypes. METHODS AND RESULTS: Selected
      prothrombotic markers were studied in 68 subjects: 34 hyperlipidemic subjects
      with familial combined hyperlipidemia and 34 controls. FCHL patients exhibited
      significantly higher Thrombin-Antithrombin complex (TAT), activated coagulation
      factor XII (F XIIa), von Willebrand Factor (vWF), Plasminogen Activator Inhibitor
      1 (PAI-1) and tissue derived Plasminogen Activator (t-PA) values in comparison to
      controls. Within the subgroup of familial combined hyperlipidemia subjects,
      elevated PAI-1 activity and soluble Thrombomodulin levels were particularly
      associated with features of the metabolic syndrome, including hyperinsulinemia,
      hypertriglyceridemia and predominance of small dense low density lipoprotein
      (LDL). CONCLUSIONS: A general pattern of activated blood coagulation and
      endothelial activation is present in all hyperlipidemic subjects studied,
      independent of metabolic phenotype. In those familial combined hyperlipidemia
      subjects with features of the metabolic syndrome, impaired fibrinolysis can
      provide an additional cardiovascular risk factor.

PMID- 15262192
TI  - Intima-media thickness of elastic and muscular arteries of young women with
      polycystic ovaries.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) occurs in around 10% women of
      reproductive age and is characterised by obesity, hyperandrogenism, insulin
      resistance and adverse lipid profile. This suggests that these women may be at an
      increased risk of coronary artery disease at a young age. The objective of this
      study was to measure the intima-media thickness (IMT) in the carotid bulb (CB),
      common carotid (CCA) and common femoral (CFA) arteries in young women aged less
      than 35 years. METHODS: A total of 43 age-matched women were recruited; 19
      symptomatic women with PCOS, 12 asymptomatic women with polycystic ovaries (PCO)
      and 12 staff volunteers with normal ovaries on transvaginal scan. All subjects
      were examined with ultrasound wall tracking system for IMT measurements. Their
      age, body mass index, heart rate, systolic and diastolic blood pressures, fasting
      endocrine and biochemical parameters were also measured. RESULTS: The IMT
      measurements were significantly higher in both the CFA and the CCA in young women
      with PCOS compared with controls (CFA, 0.74 +/- 0.30 mm versus 0.42 +/- 0.078 mm,
      P < 0.001 and CCA, 0.54 +/- 0.11 mm versus 0.40 +/- 0.01 mm, respectively, P <
      0.006). After adjustment for known risk factors, the IMT in both the femoral and
      carotid arteries remained highly significant. CONCLUSIONS: The results of this
      study suggest that PCOS affects femoral and carotid wall mechanics leading to
      premature sub-clinical atherosclerosis in young women with PCOS and may lead to
      the development of new strategies for screening.

PMID- 15262193
TI  - Serum creatinine predicts mortality in patients with peripheral artery disease:
      influence of diabetes and hypertension.
AB  - BACKGROUND: Patients with renal insufficiency tend to suffer from advanced
      atherosclerosis and exhibit a reduced life expectancy. We investigated the
      association of renal impairment, traditional cardiovascular risk factors and all
      cause mortality in patients with symptomatic peripheral artery disease (PAD).
      METHODS: We studied 515 patients with advanced PAD (intermittent claudication, n
      = 410; critical ischemia, n = 105). Cardiovascular risk profile and calculated
      glomerular filtration rate (GFR) were obtained at baseline and patients were
      followed for median 21 months (interquartile range 12 to 25) for mortality.
      RESULTS: Sixty-five patients (13%) died. Cumulative survival rates at 6, 12, and
      24 months were 97%, 95%, and 89%, respectively. Adjusted hazard ratios for
      mortality according to decreasing quartiles of GFR were 1.2, 2.5, and 5.9
      compared to the highest quartile (P < 0.001). The association between renal
      impairment and mortality was independent of diabetes and hypertension, suggesting
      that decreased GFR adds to the prognostic value of traditional cardiovascular
      risk factors. CONCLUSION: Renal impairment is associated with an increased risk
      for mortality in patients with advanced peripheral artery disease, irrespective
      of the coincidence of arterial hypertension and diabetes mellitus. This suggests
      that impaired renal function exerts an unfavorable effect on patient's outcome,
      independently of these cardiovascular and renal risk factors.

PMID- 15262194
TI  - Impact of Vitamin E supplementation on lipoprotein peroxidation and composition
      in Type 1 diabetic patients treated with Atorvastatin.
AB  - OBJECTIVE: To investigate the impact of Vitamin E on lipids and peroxidation
      during statin treatment. RESEARCH DESIGN AND METHODS: T1DM patients with high
      cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or
      d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood
      biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation
      at inclusion and after 3 and 6 months. RESULTS: Serum cholesterol and
      triglycerides decreased to the same extent (29 and 21% respectively) in both
      groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P <
      0.0001, between-group comparison by repeated measures ANOVA) but relative to
      lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of
      thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in
      AP and did not change in AE (P = 0.02). The lagtime for the production of
      fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma
      malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted
      for lipids. CONCLUSIONS: In T1DM Vitamin E supplements do not affect the lowering
      of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the
      increase of in vitro peroxidation caused by Atorvastatin but do not achieve the
      decreases observed in patients not receiving lipid-lowering drugs. These results
      indicate that the antioxidant effect of Vitamin E is attenuated when given in
      conjunction with this statin.

PMID- 15262195
TI  - Effectiveness of HMG-CoA reductase inhibitors is modified by the ACE insertion
      deletion polymorphism.

PMID- 15262196
TI  - Blood donation, iron depletion and vascular integrity.

PMID- 15262198
TI  - Contribution of glial cells and pericytes to the mRNA profiles of P-glycoprotein
      and multidrug resistance-associated proteins in an in vitro model of the blood
      brain barrier.
AB  - P-glycoprotein (P-gp) and the multidrug resistance-associated proteins (MRP),
      whose expression is associated with multidrug resistance, have been recently
      located in the brain capillary endothelial cells (BCEC) forming the blood-brain
      barrier (BBB), without taking into account a possible influence or contribution
      of glial cells and pericytes. Using semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR), the present study analysed the
      transcriptional expression of P-gp and the seven homologues of MRP transporters
      in BCECs in solo culture or in an in vitro model of the BBB consisting of a co
      culture of BCECs and glial cells. Pericytes, glial cells, isolated brain
      capillaries and bovine grey matter extracts were also tested. P-gp mRNA, absent
      in glial cells, was found in brain capillaries and in co-cultured BCECs with an
      increased signal compared to the in solo culture. No amplification was observed
      in pericytes or grey matter. While MRP2, MRP3 and MRP7 remained undetected, MRP1,
      absent in capillaries or grey matter, was amplified in BCECs, glial cells and
      pericytes. MRP4 gave a low signal in most cultures. MRP5 was ubiquitously
      expressed, displaying a potent signal in all conditions. In spite of its presence
      in cultured glial cells, MRP6 mRNA expression appeared to be restricted to BCECs,
      with the same upregulation in the co-cultured condition as observed with P-gp.
      Moreover, MRP6 was the only transporter whose endothelial mRNA expression was
      influenced by the presence of pericytes. The tissue distribution of the
      expression of these transporters and the contribution of the different cell
      populations are discussed.

PMID- 15262199
TI  - Expression of the receptor for advanced glycation end products in Huntington's
      disease caudate nucleus.
AB  - The accumulation of amyloid-beta and increased expression of its receptor RAGE
      (the receptor for advanced glycation end products) have been implicated in the
      pathogenesis of Alzheimer's disease (AD). Here we have used immunohistochemistry
      and double labelling to localize RAGE expression in Huntington's disease (HD)
      caudate nucleus (CN). Results showed that RAGE is expressed in at least two cell
      types in the CN, medium spiny projection neurons and astrocytes, with stronger
      staining in astrocytes than in neurons. The percentage of the total number of
      neurons positive for RAGE was significantly higher in G2 and G3 HD CN when
      compared with controls. What is more interesting however was the heterogeneous
      distribution of RAGE staining in CN. In controls, astrocytic RAGE staining was
      seen only in the superficial layer of the subependymal layer (SEL). In G1 HD
      cases, staining was seen throughout the entire width of SEL but extended into the
      CN in G2, 3 and 4. Neuronal RAGE staining was stronger in the medial CN than in
      the lateral CN in control and G1 cases. In G2, 3 and 4 cases, this staining
      gradient was not observed; more neuronal RAGE staining was however seen in the
      dorsal part of the CN when compared with the ventral part. The distribution of
      RAGE staining in neurons appeared to correlate with the ordered cell death seen
      in HD CN. Identification of the ligand for RAGE in HD brain and further
      functional studies are needed to clarify the role of RAGE in the pathogenesis of
      HD.

PMID- 15262200
TI  - Neuronal network properties of human teratocarcinoma cell line-derived neurons.
AB  - Understanding the structural and functional development of neurons in networks
      has a high impact to estimate the potentials for restorative therapies. Neurons
      derived from the human NT2 cell line (hNT) formed networks with a clustered
      neuritic architecture in vitro, whereas primary dissociated embryonic rat
      cortical neurons (Cx) displayed a more homogenous cell assembly. Spontaneous
      spikes of both cell types were recorded on microelectrode arrays within 2 weeks
      after seeding, but hNT showed a mostly uncorrelated firing pattern in contrast to
      Cx with highly synchronized bursting. hNT neurons were less sensitive to TTX
      (IC50 = 5.7 +/- 0.1 nM vs. IC50 = 1.1 +/- 0.2 nM), magnesium (IC50 = 1.83 +/-
      0.01 mM vs. IC50 = 0.161 +/- 0.023 mM), and APV (IC50 > 100 microM vs. IC50 = 18
      microM). We conclude that embryonic cortical neurons and hNT neurons have
      different network properties. This should be carefully considered before hNT
      neurons are used in therapeutic approaches, e g., central nervous system (CNS)
      grafting.

PMID- 15262201
TI  - The unique inhibitory potentials in motoneurons that occur during active sleep
      are comprised of minimal unitary potentials.
AB  - Loss of muscle tone during active (rapid-eye-movement, REM) sleep is due to the
      inhibition of motoneurons. This inhibition is manifest in high-gain intracellular
      electrophysiological records as hyperpolarizing synaptic noise, which includes
      large amplitude active sleep-specific inhibitory postsynaptic potentials (IPSPs).
      We report here evidence that the large active sleep-specific IPSPs are comprised
      of a small number of minimal unitary potentials that are characterized by fast
      rise-times (10-90% rise-times < or = 0.75 ms); they are present in high-gain
      records during quiet sleep or during active sleep where they are intermingled
      with larger active sleep-specific IPSPs with 10-90% rise-times > or = 1.00 ms and
      amplitudes that are integer multiples of the minimal unitary potentials. In
      hypoglossal motoneurons, the amplitude of these minimal unitary potentials
      averaged 0.33 +/- 0.04 mV (mean +/- S.D., n = 6). It is concluded that the large
      IPSPs with slow rise-times that are observed in motoneurons during active sleep
      are due to the nearly simultaneous arrival of multiple (< or = 5) minimal unitary
      potentials. We hypothesize that the same inhibitory interneurons that produce
      small IPSPs with fast rise-times during quiet sleep are also responsible for the
      large amplitude active sleep-specific IPSPs.

PMID- 15262202
TI  - Combined cyclosporine-A and methylprednisolone treatment exerts partial and
      transient neuroprotection against ischemic stroke.
AB  - We investigated the neuroprotective effects of immunosuppressant cyclosporine-A
      (CsA) and the anti-inflammatory methylprednisolone (MP) in a stroke model. Adult
      Sprague-Dawley rats underwent middle cerebral artery (MCA) occlusion then were
      randomly treated with either: low dose CsA, MP, low dose CsA plus MP, high dose
      CsA, or vehicle. Ischemic animals that received low dose CsA, MP or vehicle
      displayed profound motor and neurological impairments at days 1-3 after stroke.
      In contrast, ischemic animals that received high dose CsA exhibited near normal
      motor and neurological functions throughout the test period. Of note, ischemic
      animals that received low dose CsA plus MP showed significantly less motor and
      neurological deficits at day 1, but thereafter displayed behavioral impairments.
      Histological analysis at 3 days post-stroke revealed that only those ischemic
      animals treated with high dose CsA had significantly reduced cerebral infarcts.
      This study is the first report to demonstrate partial and transient
      neuroprotection against stroke by low dose CsA when combined with MP.

PMID- 15262203
TI  - Sleep deprivation impairs spatial memory and decreases extracellular signal
      regulated kinase phosphorylation in the hippocampus.
AB  - Loss of sleep may result in memory impairment. However, little is known about the
      biochemical basis for memory deficits induced by sleep deprivation. Extracellular
      signal-regulated kinase (ERK) is involved in memory consolidation in different
      tasks. Phosphorylation of ERK is necessary for its activation and is an important
      step in mediating neuronal responses to synaptic activities. The aim of the
      present study was to determine the effects of total sleep deprivation (TSD) on
      memory and ERK phosphorylation in the brain. Rats were trained in Morris water
      maze to find a hidden platform (a spatial task) or a visible platform (a
      nonspatial task) after 6 h TSD or spontaneous sleep. TSD had no effect on spatial
      learning, but significantly impaired spatial memory tested 24 h after training.
      Nonspatial learning and memory were not impaired by TSD. Phospho-ERK levels in
      the hippocampus were significantly reduced after 6 h TSD compared to the controls
      and returned to the control levels after 2 h recovery sleep. Total ERK1 and ERK2
      were slightly increased after 6 h TSD and returned to the control levels after 2
      h recovery sleep. These alterations were not observed in the cortex after TSD.
      Protein phosphotase-1 and mitogen-activated protein kinase phosphatase-2, which
      dephosphorylates phospho-ERK, were also measured, but they were not altered by
      TSD. The impairments of both spatial memory and ERK phosphorylation indicate that
      the hippocampus is vulnerable to sleep loss. These results are consistent with
      the idea that decreased ERK activation in the hippocampus is involved in sleep
      deprivation-induced spatial memory impairment.

PMID- 15262204
TI  - Quinolinic acid promotes seizures and decreases glutamate uptake in young rats:
      reversal by orally administered guanosine.
AB  - Quinolinic acid (QA) has been used as a model for experimental overstimulation of
      the glutamatergic system. Glutamate uptake is the main mechanism involved in the
      maintenance of extracellular glutamate below toxic levels. Guanosine systemically
      administered prevents quinolinic acid-induced seizures in adult mice and
      increases basal glutamate uptake by cortical astrocyte culture and slices from
      young rats. The immature brain differs from the adult brain in its susceptibility
      to seizures, seizure characteristics, and responses to antiepileptic drugs (AED).
      Here we investigated the effect of guanosine p.o. on QA-induced seizures in young
      rats (P12-14) and upon ex vivo glutamate uptake by cortical slices from these
      animals. I.c.v. infusion of 250 nmol QA induced seizures in all animals and
      decreased glutamate uptake. I.p. injection of MK-801 and phenobarbital 30 min
      before QA administration prevented seizures in all animals. Guanosine (7.5 mg/kg)
      75 min before QA prevented seizures in 50% of animals as well as prevented the
      decrease of glutamate uptake in the protected animals. To investigate if the
      anticonvulsive effect of guanosine was specific for QA-induced seizures, the
      picrotoxin-induced seizures model was also performed. Pretreatment with
      phenobarbital i.p. (60 mg/kg-30 min) prevented picrotoxin-induced seizures in all
      animals, whereas guanosine p.o. (7.5 mg/kg-75 min) and MK-801 i.p. (0.5 mg/kg-30
      min) had no effect. Thus, guanosine protection on the QA-induced seizures in
      young rats and on the decrease of glutamate uptake showed some specificity degree
      towards the QA-induced toxicity. This points that guanosine could be considered
      for treatments of epilepsy, and possibly other neurological disorders in
      children.

PMID- 15262205
TI  - Estrogen selectively increases sensory nociceptor innervation of arterioles in
      the female rat.
AB  - Differences exist in vascular function and disease susceptibility in males and
      females, and estrogen is apparently a primary factor. One mechanism by which
      estrogen may influence vascular function is by affecting vasomotor innervation.
      We have shown previously that estrogen increases calcitonin gene-related peptide
      (CGRP)-immunoreactive sensory innervation of the rat mammary gland, but it is not
      known if this occurs in other tissues. The objective of this study was to
      determine if estrogen modulates CGRP-immunoreactive innervation of vascular and
      non-vascular tissues. Ovariectomized adult virgin female rats were implanted with
      pellets containing 17beta-estradiol or placebo. After 7 days, innervation was
      examined in the external ear, jejunal mesenteric arterioles, superficial
      epigastric, femoral, and uterine arteries, and foot skin. Immunofluorescence
      microscopy of the external ear pinna revealed increased CGRP-immunoreactive
      sensory innervation in estrogen-treated rats, and this was attributable
      specifically to increased innervation of arterioles. Tyrosine hydroxylase
      immunoreactive innervation was unchanged. Total nerve density, revealed by the
      pan-neuronal marker PGP 9.5, was also greater after estrogen treatment, implying
      structural proliferation of nociceptor vasodilator fibers. Mesenteric arteriolar
      CGRP-immunoreactive nerve density was also selectively increased by estrogen
      treatment. However, estrogen did not affect CGRP-immunoreactive nerve density of
      superficial epigastric, femoral, or uterine arteries, or foot skin. Therefore,
      estrogen increases sensory innervation of arterioles, but not of large arteries
      or skin. We conclude that sensory nociceptor vasodilatory innervation of
      arterioles is selectively enriched by estrogen, which may influence
      cardiovascular function in health and disease.

PMID- 15262206
TI  - Expression of glutamate receptors and calcium-binding proteins in the retina of
      streptozotocin-induced diabetic rats.
AB  - This study was aimed to investigate the expression of glutamate receptors and
      calcium-binding proteins in 1- and 4-month/s (mo) streptozotocin (STZ)-induced
      diabetic rats. Upregulation of glutamate receptors' [N-methyl-D-aspartate
      receptor (NMDAR)1 and GluR2/3] immunoreactivities was observed in the ganglion,
      amacrine and bipolar cells as well as in the inner and outer plexiform layers
      (IPL and OPL) in 1 mo diabetes and was further enhanced at 4 mo. Immunoreactivity
      of calcium-binding proteins (calbindin and parvalbumin) was also concomitantly
      increased. The present results suggest that upregulation of glutamate receptors
      and calcium-binding proteins may reflect changes of the glutamate and calcium
      metabolism in the diabetic retina. It is speculated that the above changes in the
      IPL and OPL may be linked to alteration of synaptic transmission in the diabetic
      retina.

PMID- 15262207
TI  - In vivo influence of ceramide accumulation induced by treatment with a
      glucosylceramide synthase inhibitor on ischemic neuronal cell death.
AB  - It has been shown that exogenous ceramide induces delayed neuronal death (DND) of
      cultured hippocampal neurons. To evaluate the role of endogenous ceramide in
      ischemic DND, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2
      decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to generate ceramide in
      gerbil hippocampi in vivo. The trimethylsilylated derivatives of ceramide were
      analyzed directly by gas chromatography mass spectrometry, after separation with
      high-performance thin-layer chromatography. The ceramide compositions in vehicle
      hippocampus consisted mainly of C18:0 fatty acyl sphingosine (87.9%), with C16:0
      and C20:0 ceramides being minor components (7.1% and 5.1%, respectively).
      Ceramide level in the hippocampi from gerbils subjected to D-PDMP treatment was
      1.5-fold higher than those from vehicle-treated gerbils. In spite of the
      accumulation of ceramide observed in the D-PDMP group, the histological studies
      did not reveal any ischemic neuronal death in hippocampal CA1 neurons with the
      gerbils that had been subjected to a sham operation (2-min sublethal ischemia).
      These results suggest that the ceramide accumulation induced by blocking the de
      novo synthesis of glucosylceramide with D-PDMP may be independent of the
      metabolic pathway underlying ischemic DND.

PMID- 15262208
TI  - Alterations in food intake by opioid and dopamine signaling pathways between the
      ventral tegmental area and the shell of the nucleus accumbens.
AB  - Reward is an important factor motivating food intake in satiated animals. Two
      sites involved in the reward response are the ventral tegmental area (VTA) and
      the nucleus accumbens shell region (sNAcc), between which communication is
      partially regulated by opioids and dopamine (DA). Previous studies have shown
      that the mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) dose
      dependently enhances food intake in satiated animals when injected into either
      the VTA or the sNAcc. The enhanced intake elicited by DAMGO injected into the
      sNAcc was dose-dependently blocked by injection of naltrexone (NTX) bilaterally
      into the VTA, indicating an opioid-dependent signaling pathway from the sNAcc to
      the VTA in mediation of food intake. In the present study, we cannulated animals
      bilaterally in both the VTA and the sNAcc to further study the nature of opioid-
      and DA-dependent communication between the sites. Food intake elicited by DAMGO
      (2 or 5 nmol) injected unilaterally into the VTA was dose-dependently diminished
      by bilateral injection of NTX (2.5, 5, and 25 g/side) or the D1 antagonist SCH
      23390 (3, 1, 0.3, 0.15, 0.05, and 0.015 nmol/side) into the sNAcc. When DAMGO (5
      nmol) was injected into the sNAcc, the resulting food intake was decreased by
      doses of SCH 23390 ranging from 0.05 to 100 nmol/side injected bilaterally into
      the VTA, but not by equimolar doses of Raclopride, a D2 antagonist. These
      results, combined with previous findings, suggest a signaling pathway between the
      VTA and the sNAcc in which opioids and DA facilitate feeding in an interdependent
      manner.

PMID- 15262209
TI  - Antisense directed at the Abeta region of APP decreases brain oxidative markers
      in aged senescence accelerated mice.
AB  - Amyloid beta-peptide (Abeta) is known to induce free radical-mediated oxidative
      stress in the brain. Free radical-mediated damage to the neuronal membrane
      components has been implicated in the etiology of Alzheimer's disease (AD). Abeta
      is produced by proteolytic processing of the amyloid precursor protein (APP). The
      senescence accelerated mouse prone 8 (SAMP8) strain was developed by phenotypic
      selection from a common genetic pool. The SAMP8 strain exhibits age-related
      deterioration in memory and learning as well as Abeta accumulation, and it is
      considered an effective model for studying brain aging in accelerated senescence.
      Previous research has shown that a phosphorothiolated antisense oligonucleotide
      directed against the Abeta region of APP decreases the expression of APP and
      reverses deficits in learning and memory in aged SAMP8 mice. Consistent with
      other reports, our previous study showed that 12-month-old SAMP8 mice have
      increased levels of oxidative stress markers in the brain compared with that in
      brains from 4-month-old SAMP8 mice. In the current study, 12-month-old SAMP8 mice
      were treated with antisense oligonucleotide directed against the Abeta region of
      APP, and the oxidative markers in brain were decreased significantly. Therefore,
      we conclude that Abeta may contribute to the oxidative stress found in aged SAMP8
      mice that have learning and memory impairments. These results are discussed in
      reference to AD.

PMID- 15262210
TI  - Nicotine-mediated plasticity in robust nucleus of the archistriatum of the adult
      zebra finch.
AB  - Activation of neuronal nicotinic acetylcholine receptors (nAChRs) modulates the
      induction of long-term potentiation (LTP), a possible cellular mechanism for
      learning. This study was undertaken to determine the effects of activation of
      nAChRs by nicotine on long-term plasticity in the songbird zebra finch, which is
      a valuable model to study synaptic plasticity and its implications to behavioral
      learning. Electrophysiological recordings in the robust nucleus of the
      archistriatum (RA) in adult zebra finch brain slices reveal that tetanic
      stimulation alone does not produce LTP. However, LTP is induced by such
      stimulation in the presence of nicotine. The nicotine-mediated LTP is blocked by
      dihydro-beta-erythroidine (DHbetaE, 1 microM), an antagonist having a greater
      effect against nAChRs containing the alpha 4 subunit. In the presence of
      methyllcaconitine (MLA, 10 nM), an antagonist of nAChRs containing the alpha 7
      subunit, a long-term depression (LTD) is unmasked, implicating a bi-directional
      type of plasticity in the zebra finch RA, which is modulated by differential
      activation of nAChR subtypes. Intracellular recordings from single neurons show a
      depression of the afterhyperpolarization (AHP) and an increase in frequency of
      evoked and spontaneous action potentials in the presence of nicotine. These
      results suggest that nicotinic cholinergic mechanisms may play a critical role in
      synaptic plasticity in the zebra finch song system and thereby influence song
      learning and plasticity.

PMID- 15262211
TI  - Colorectal distension-induced suppression of a nociceptive somatic reflex
      response in the rat: modulation by tissue injury or inflammation.
AB  - Inhibition of somatic nociception by conditioning noxious visceral stimulation
      was studied under pathophysiological conditions in rats. Viscero-somatic
      inhibition was enhanced following visceral inflammation and reduced by a somatic
      heat injury. The enhancement was reversed by an N-methyl-D-aspartate (NMDA)
      receptor antagonist. These changes in viscero-somatic inhibition may be explained
      by corresponding changes in excitatory drives evoked by conditioning and test
      stimulation, although disinhibition may contribute to reduction of inhibition
      following somatic injury.

PMID- 15262212
TI  - Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase
      inhibitor, in NMDA-induced neurotoxicity in the rat retina.
AB  - RhoA, a key protein involved in cytoskeleton regulation modulating neurogenesis
      and neural plasticity, has been implicated in a variety of cellular functions
      including the modulation of N-methyl-D-aspartate (NMDA) receptor activity. We
      examined its possible involvement in NMDA-induced excitotoxicity in the retina,
      and evaluated the neuroprotective effect of fasudil, a Rho kinase inhibitor, in
      this model of neurotoxicity. RhoA protein levels in NMDA-treated retinas were
      assessed by Western blot analysis and localized by immunohistochemistry. Fasudil
      (10(-6)-10(-4) M together with 4 x 10(-2) M NMDA) was given intravitreally and
      its effect was evaluated by counting the number of cells in the ganglion cell
      layer (GCL), measuring the thickness of the inner plexiform layer (IPL), and
      measuring retinal Thy-1 mRNA levels at 5 days after injection. Western blot
      analysis showed a transient increase in the level of retinal RhoA and ROCKII
      proteins at 1 day after NMDA injection, and that this increment was significantly
      prevented by simultaneous injection of fasudil. Immunohistochemistry showed that
      NMDA induced a substantial increase in RhoA immunoreactivity in the GCL and the
      IPL. Fasudil injection reduced cell loss in the GCL and the reduction in IPL
      thickness after NMDA injection. The reduction in Thy-1 mRNA levels by NMDA was
      also significantly attenuated by concomitant injection of fasudil. These results
      suggest that RhoA and ROCKII are upregulated and may be involved in NMDA-induced
      retinal neurotoxicity, and that fasudil is neuroprotective against glutamate
      related excitotoxicity.

PMID- 15262213
TI  - Estrogen attenuates neuronal excitability in the insular cortex following middle
      cerebral artery occlusion.
AB  - The current investigation examined the role of estrogen in the insular cortex
      (IC) under both normal and ischemic conditions. Experiments were done in
      anaesthetized male Sprague-Dawley rats. The effect of systemic 17beta-estradiol
      (estrogen) administration on levels of amino acids and of endogenous estrogen
      obtained by microdialysis and its effect on neuronal activity of cells located in
      the insular cortex were measured in the absence of, and following permanent
      occlusion of, the right middle cerebral artery (MCA). In normal rats, intravenous
      (i.v.) injection of estrogen resulted in a significant increase (greater than 25
      spikes/bin) in the spontaneous activity of neurons located within the insular
      cortex, while there was a significant decrease in gamma-aminobutyric acid (GABA)
      levels measured in IC dialysate. Middle cerebral artery occlusion (MCAO) resulted
      in a biphasic response consisting of a transient increase in the extracellular
      concentration of glutamate, aspartate, and GABA, followed by sustained elevations
      in glutamate and aspartate, but reduced GABA levels 4 h post-MCAO. MCAO also
      resulted in a significant increase in neuronal activity in the IC (from 28 +/- 9
      to 120 +/- 88 spikes/bin). This MCAO-induced excitation was completely blocked
      following the prior intravenous administration of estrogen. Systemic estrogen
      administration also resulted in a delay in the progression and decrease in the
      final infarct volume by approximately 56%. Taken together, these results suggest
      that under normal conditions, estrogen excites neurons in the insular cortex by
      decreasing GABA release (disinhibition) and it plays a role in attenuating the
      MCAO-induced excitability and death of these neurons.

PMID- 15262214
TI  - Stability of synaptic plasticity in the adult rat visual cortex induced by
      complex environment exposure.
AB  - Studies have demonstrated the effects of complex environment (EC) housing on
      brain plasticity both during postnatal development and in adulthood, but it is
      not clear how long these plastic changes persist nor what happens when
      environmental exposure is discontinued. Here we examined layer IV in the visual
      cortex of adult male rats for the: (1) effects of EC housing on synaptic
      plasticity, and (2) persistence of the synaptic changes after withdrawal from the
      complex environment. Fifty-eight adult male Long Evans rats were assigned to
      either: EC, socially paired housing (SC), or individual housing (IC). These rats
      remained in their assigned environment for 30 days. After 30 days, all rats in SC
      and some animals from the EC and IC groups were removed and perfused. The
      remaining animals in EC were then assigned to either remain in EC (ECEC) or be
      subsequently housed in IC (ECIC) for another 30 days. Similarly, rats in the IC
      group either remained in IC (ICIC) or were subsequently housed in EC (ICEC) for
      another 30 days. Electron microscopy results showed that all rats exposed to EC
      had significantly more synapses/neuron compared to SC, IC, and ICIC animals.
      Longer exposure to EC (ECEC) did not result in statistically more synapses per
      neuron; however, decreased neuron volume was seen. EC-induced synaptic changes
      persisted for an additional 30 days after withdrawal from EC (ECIC) confirming
      that EC-induced plastic changes occur in the brain regardless of age and
      indicating that once changes occur they tend to persist.

PMID- 15262215
TI  - Correlation of neuron-specific enolase and S100B with histological cerebral
      damage in fetal sheep after severe asphyxia.
AB  - Experimental brain damage was induced in 16 fetal sheep by umbilical cord
      occlusion, and the correlation of neuron-specific enolase (NSE) or S100B with the
      damage grade was investigated in seven fetuses. Significant correlations of
      damage degree with NSE (p = 0.016) and S100B (p = 0.018) in serum 2 h after
      insult were shown by Spearman's test. These findings suggest that they represent
      potentially useful markers for detecting brain damage at early stage after
      ischemic insult.

PMID- 15262216
TI  - Age-related changes in erythropoietin immunoreactivity in the cerebral cortex and
      hippocampus of rats.
AB  - Although oxidative stress may influence the fluid properties of blood, resulting
      in a potential decrement in blood flow and oxygen delivery to the brain during
      aging, very little is known about age-related changes in Epo expression.
      Therefore, we examined age-related changes in Epo expression in the cerebral
      cortex and hippocampus with an immunohistochemical technique. In aged rats, there
      was a significant decrease in Epo immunoreactivity in the pyramidal cells in the
      cortical regions. In the hippocampus of adult rats, a distinct immunoreactivity
      pattern was observed in the CA1-3 areas and dentate gyrus. In aged hippocampus,
      Epo immunoreactivity was significantly deceased in the pyramidal layer of CA1
      regions, and the granule cell layer of dentate gyrus. It was noted that there was
      distinct pattern of Epo immunoreactivity in the pyramidal layer of CA2-CA3 region
      of aged rats. Epo immunoreactivity was relatively strong, but was observed only
      in the periphery of the cytoplasm. The first demonstration of age-related
      decreases in Epo expression in the cerebral cortex and hippocampus may provide
      useful data for investigating the pathogenesis of age-related neurodegenerative
      diseases, suggesting that age-related decreases in Epo may contribute to
      degenerative events following age-related decreases in brain flow and oxygen
      supply.

PMID- 15262217
TI  - A test of the role of metaworry in the prediction of worry severity in an elderly
      sample.
AB  - Wells (Behav. Cogn. Psychother. 23 (1995) 301) proposed a cognitive model, which
      distinguishes between two kinds of worry: type I worry (focused on external
      things) and type II worry or metaworry (worry about one's own thoughts and
      worry). Wells' model assigns a central role to metaworry in the development of
      excessive worry, and Wells and Carter (Behav. Res. Ther. 37 (1999) 585) found in
      a college sample that metaworry predicted the level of trait worry after
      controlling for trait anxiety and type I worry. The present study replicated
      their investigation with a Spanish elderly sample and supported Wells'
      predictions that metaworry plays a significant role in the prediction of trait
      worry in contrast to type I worries, even when trait anxiety or perceived
      uncontrollability over worry are controlled.

PMID- 15262218
TI  - Fear activation and distraction during the emotional processing of claustrophobic
      fear.
AB  - We tested several hypotheses derived from the emotional processing theory of fear
      reduction by manipulating claustrophobic participants' focus of attention during
      in vivo exposure. Sixty participants displaying marked claustrophobic fear were
      randomized to one of four exposure conditions. Each participant received a total
      of 30-min of self-guided exposure 2-weeks after pretreatment testing. One group
      attended to threatening words and images during exposure (TW) and was compared to
      a control group that attended to neutral words and images (NW). A third group
      performed a demanding cognitive load task--a modified Seashore Rhythm Test during
      exposure (SR) and was compared to an exposure only (EO) control group. Contrary
      to prediction, the threat word manipulation was not associated with lower levels
      of fear following treatment. Consistent with prediction, the distraction
      manipulation resulted in less fear reduction at post-treatment. Treatment process
      analyses revealed that the negative effects of distraction on treatment outcome
      manifested early as slower between-trial habituation. These results and their
      relevance to emotional processing theory are discussed.

PMID- 15262219
TI  - Children's perception and interpretation of anxiety-related physical symptoms.
AB  - The present study examined children's perception and interpretation of anxiety
      related physical symptoms in a sample of 4-12-year-old primary school children (N
      = 129). Children were presented with neutral scenarios in which the main
      character experienced an anxiety-related physical symptom (e.g., hands trembling,
      heart beating very fast), and asked to attribute various emotions to this
      character. Children were also interviewed about idiosyncratic experiences with
      anxiety-related physical symptoms. Results showed that physical symptoms were
      associated with a broad range of emotions. "Hands trembling", "heart beating
      fast", and "difficulties with breathing" were the only symptoms that were more
      frequently linked to fear than to other emotions. Furthermore, developmental
      patterns were found for fear-related interpretations of physical symptoms. That
      is, from the age of 7, children more frequently associated physical symptoms to
      fear. Finally, children reported to experience anxiety-related physical symptoms
      in daily life, although frequently not in relation to fearful situations and
      circumstances.

PMID- 15262220
TI  - A preliminary test of the role of experiential avoidance in post-event
      functioning.
AB  - Experiential avoidance is the unwillingness to experience unwanted thoughts,
      emotions, or bodily sensations and an individual's attempts to alter, avoid, or
      escape those experiences. The aim of the current studies was to broaden previous
      research indicating that experiential avoidance often leads to the development
      and maintenance of psychological distress. Results indicated that experiential
      avoidance is significantly correlated with psychological distress and post
      traumatic symptomatology over and above other measures of psychological
      functioning. Limitations and implications for treatment and prevention of
      psychological distress are discussed.

PMID- 15262221
TI  - Differential relations between heart rate and skin conductance, and public
      speaking anxiety.
AB  - The present pilot study tested whether the lack of consistent findings of
      relations between autonomic nervous system (ANS) activity and non-clinical levels
      of public speaking anxiety (PSA) can be explained by methodology. An ambulatory
      protocol was utilised to test whether the interaction of belief structure with
      each of an undergraduate student speaker's heart rate and skin conductance level
      predicted state speech anxiety better than their linear summation. Results
      suggest that in a non-clinical population, the interaction of ANS activity and
      belief structure is an important determinant of PSA, and may account for variable
      findings in the literature.

PMID- 15262222
TI  - Calcineurin B protects calcineurin A against denaturation by urea.
AB  - Calcineurin (CN), a heterodimer composed of a catalytic subunit, calcineurin A
      (CNA) and regulatory subunit, calcineurin B (CNB), is involved in many cellular
      processes. We investigated the denaturation of CNA by urea in the presence or
      absence of CNB and found that CNB protected CNA against urea. The phosphatase
      activity of CNA that had been exposed to low urea concentrations (below 4 M), in
      the presence CNB, was higher than that of the separately urea-treated subunits
      mixed just prior to assay. In order to analyze the protection of CNA by CNB, we
      investigated the K(m) and V(max), and intrinsic fluorescence, of CNA that had
      been exposed to various concentrations of urea in the presence or absence of CNB.
      CN had an increased V(max) and decreased K(m) when exposed to 1 to 2 M urea. In
      addition, the kinetic parameters and intensity of intrinsic fluorescence of the
      AB complex and isolated subunits were quite different in 3 M urea. These results
      indicate that CNB not only plays an important role in regulating CNA, but also
      protects it against denaturation by urea.

PMID- 15262223
TI  - Starvation-sensitive UCP 3 protein expression in thymus and spleen mitochondria.
AB  - To date, UCP 3 has only been associated with skeletal muscle and brown adipose
      tissue (BAT). Using RT-PCR/PCR methodology, we show that human spleen and human
      thymus contain UCP 3. In addition, using peptide antibodies, previously
      demonstrated to be selective for UCP 3, we show that UCP 3 protein is present in
      mitochondria isolated from rat thymus and mitochondria isolated from
      reticulocytes, monocytes and lymphocytes of rat spleen. UCP 3 protein expression
      is also starvation-sensitive. UCP 3 abundance is augmented in mitochondria
      isolated from thymus and mitochondria isolated from lymphocytes of the spleen
      from fasted rats when compared to fed controls. The results are consistent with a
      role for UCP 3 in developing lymphocytes, thymus atrophy and fatty acid
      utilisation in spleen and thymus.

PMID- 15262224
TI  - Identification, characterization, and site-directed mutagenesis of recombinant
      pentachlorophenol 4-monooxygenase.
AB  - In a previous study, we constructed a three-dimensional (3D) structure of
      pentachlorophenol 4-monooxygenase (PcpB). In this study, further analyses are
      performed to examine the important amino acid residues in the catalytic reaction
      by identification of the proteins with mass spectrometry, circular dichroism (CD)
      and UV spectrometry, and determination of kinetic parameters. Recombinant
      histidine-tagged PcpB protein was produced and shown to have a similar activity
      to the native protein. Mutant proteins of PcpB were then produced (F85A, Y216A,
      Y216F, R235A, R235E, R235K, Y397A and Y397F) on the basis of the proposed 3D
      structure. The CD spectra of the proteins showed that there were no major changes
      in the structures of the mutant proteins, with the exception of R235E. Steady
      state kinetics showed a 20-fold reduction in k(cat)/K(m) and a ninefold increase
      in K(m) for Y216F and a threefold reduction in k(cat)/K(m) and a sixfold increase
      in K(m) for Y397F compared to the wild type. On the other hand, the value of
      k(cat)/K(m) of R235K mutant was the same as that of wild type. As a result, it
      was confirmed that Y216 and Y397 play an important role with respect to the
      recognition of the substrate.

PMID- 15262225
TI  - Proteolytic cleavage of the hyperthermophilic topoisomerase I from Thermotoga
      maritima does not impair its enzymatic properties.
AB  - Using limited proteolysis, we show that the hyperthermophilic topoisomerase I
      from Thermotoga maritima exhibits a unique hot spot susceptible to proteolytic
      attack with a variety of proteases. The remaining of the protein is resistant to
      further proteolysis, which suggests a compact folding of the thermophilic
      topoisomerase, when compared to its mesophilic Escherichia coli homologue. We
      further show that a truncated version of the T. maritima enzyme, lacking the last
      C-terminal 93 amino acids is more susceptible to proteolysis, which suggests that
      the C-terminal region of the topoisomerase may be important to maintain the
      compact folding of the enzyme. The hot spot of cleavage is located around amino
      acids 326-330 and probably corresponds to an exposed loop of the protein, near
      the active site tyrosine in charge of DNA cleavage and religation. Location of
      this protease sensitive region in the vicinity of bound DNA is consistent with
      the partial protection observed in the presence of different DNA substrates.
      Unexpectedly, although proteolysis splits the enzyme in two halves, each
      containing part of the motifs involved in catalysis, trypsin-digested
      topoisomerase I retains full DNA binding, cleavage, and relaxation activities,
      full thermostability and also the same hydrodynamic and spectral properties as
      undigested samples. This supports the idea that the two fragments which are
      generated by proteolysis remain correctly folded and tightly associated after
      proteolytic cleavage.

PMID- 15262226
TI  - Evidence for a direct but sequential binding of titin to tropomyosin and actin
      filaments.
AB  - Titin is a giant molecule that spans half a sarcomere, establishing several
      specific bindings with both structural and contractile myofibrillar elements. It
      has been demonstrated that this giant protein plays a major role in striated
      muscle cell passive tension and contractile filament alignment. The in vitro
      interaction of titin with a new partner (tropomyosin) reported here is reinforced
      by our recent in vitro motility study using reconstituted Ca-regulated thin
      filaments, myosin and a native 800-kDa titin fragment. In the presence of the
      tropomyosin-troponin complex, the actin filament movement onto coated S1 is
      improved by the titin fragment. Here, we found that two purified native titin
      fragments of 150 and 800 kDa, covering respectively the N1-line and the N2
      line/PEVK region in the I-band and known to contain actin-binding sites, directly
      bind tropomyosin in the absence of actin. We have also shown that binding of the
      800-kDa fragment with filamentous actin inhibited the subsequent interaction of
      tropomyosin with actin, as judged by cosedimentation. However, this was not the
      case if the complex of actin and tropomyosin was formed before the addition of
      the 800-kDa fragment. We thus conclude that a sequential arrangement of contacts
      exists between parts of the titin I-band region, tropomyosin and actin in the
      thin filament.

PMID- 15262227
TI  - hIscA: a protein implicated in the biogenesis of iron-sulfur clusters.
AB  - This article describes the gene called hIscA, its transcription product and
      protein (hIscA) and its putative function. We screened a human brain cDNA
      expression library with serum from a patient suffering from the autoimmune
      Sjogren's syndrome (S5:823/94). One cDNA of 1.6-kbp clone was isolated. This
      clone contains the entire coding sequence for a protein unknown in human. IscA is
      ubiquitously expressed and expression levels vary among tissues. The 15.5-kDa
      predicted protein contains a structural domain named HESB, is located in the
      mitochondria and is implicated in the biogenesis of iron-sulfur clusters. Since
      this unknown protein is related to IscA-like protein, we suggest as name for this
      protein hIscA. The recombinant protein is recognized by a rabbit polyclonal
      antiserum generated against the carboxyl extreme of the Saccharomyces cerevisiae
      orthologue Isa1. In this article, we demonstrate the functional homology between
      hIscA and Isa1 proteins using Isa1 null mutant S. cerevisiae transformed with
      hIscA in a yeast functional complementation test. We also describe the rat
      homologue to this gene.

PMID- 15262228
TI  - Purification and characterization of Acremonium implicatum alpha-glucosidase
      having regioselectivity for alpha-1,3-glucosidic linkage.
AB  - alpha-Glucosidase with a high regioselectivity for alpha-1,3-glucosidic linkages
      for hydrolysis and transglucosylation was purified from culture broth of
      Acremonium implicatum. The enzyme was a tetrameric protein (M.W. 440,000), of
      which the monomer (M.W. 103,000; monomeric structure was expected from cDNA
      sequence) was composed of two polypeptides (M.W. 51,000 and 60,000) formed
      possibly by posttranslational proteolysis. Nigerose and maltose were hydrolyzed
      by the enzyme rapidly, but slowly for kojibiose. The k(0)/K(m) value for nigerose
      was 2.5-fold higher than that of maltose. Isomaltose was cleaved slightly, and
      sucrose was not. Maltotriose, maltotetraose, p-nitrophenyl alpha-maltoside and
      soluble starch were good substrates. The enzyme showed high affinity for
      maltooligosaccharides and p-nitrophenyl alpha-maltoside. The enzyme had the alpha
      1,3- and alpha-1,4-glucosyl transfer activities to synthesize oligosaccharides,
      but no ability to form alpha-1,2- and alpha-1,6-glucosidic linkages. Ability for
      the formation of alpha-1,3-glucosidic linkage was two to three times higher than
      that for alpha-1,4-glucosidic linkage. Eight kinds of transglucosylation products
      were synthesized from maltose, in which 3(2)-O-alpha-nigerosyl-maltose and 3(2)-O
      alpha-maltosyl-maltose were novel saccharides.

PMID- 15262229
TI  - High-level production and optimization of monodispersity of 11beta-hydroxysteroid
      dehydrogenase type 1.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intraluminally
      oriented, endoplasmic reticulum (ER)-bound enzyme catalyzing the interconversion
      between inactive cortisone and hormonally active cortisol. Heterologous
      production of 11beta-HSD1, devoid of its N-terminal transmembrane segment, is
      possible but yields only small amounts of soluble protein. Here we show that the
      soluble portion of recombinant 11beta-HSD1 produced in E. coli is found mainly as
      multimeric aggregates in the absence of detergent, and to a large extent
      associated with the endogenous chaperonin GroEL and other E. coli proteins. By co
      overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein
      synthesis, we have increased the accumulation of soluble 11beta-HSD1 by more than
      one order of magnitude. Using monodispersity as a screening criterion, we have
      also optimized the purification process by evaluating various solubilizing
      systems for the chromatographic steps, finally obtaining stable monodisperse
      preparations of both human and guinea pig 11beta-HSD1. By analytical
      ultracentrifugation, we could demonstrate that 11beta-HSD1 mainly exists as a
      dimer in the solubilized state. Moreover, active site titration of human 11beta
      HSD1 revealed that at least 75% of the protein in a typical preparation
      represents active enzyme. Equilibrium unfolding experiments indicate that
      addition of inhibitor and the cofactor NADP(H) can stabilize the conformational
      stability of this enzyme in an additive manner. The outlined procedure may
      provide a general method for preparing similar proteins to oligomeric homogeneity
      and with retained biological activity.

PMID- 15262230
TI  - Isolation and purification of antifreeze proteins from skin tissues of snailfish,
      cunner and sea raven.
AB  - Antifreeze proteins/polypeptides (AFPs), which are found in diverse species of
      marine fish, are grouped into four distinct classes (types I-IV). The discovery
      of skin-specific type I AFPs established that this class contains distinct
      isoforms, liver-type and skin-type, which are encoded by separate gene families.
      In this study, type I AFPs were isolated and partially characterized from skin
      tissues of Atlantic snailfish (Liparis atlanticus) and cunner (Tautogolabrus
      adspersus). Interestingly, evidence from this study indicates that snailfish type
      I AFPs synthesized in skin tissues are identical to those circulating in their
      blood plasma. Furthermore, type II AFPs that are identical to those expressed in
      liver for export into blood were purified from sea raven (Hemitripterus
      americanus) skin tissue extracts. It is clear that epithelial tissues are an
      important source for antifreeze expression to enhance the complement of AFPs that
      protect fish from freezing in extreme cold environments. In addition, the
      evidence generated in this study demonstrates that expression of AFPs in fish
      skin is a widespread phenomenon that is not limited to type I proteins.

PMID- 15262231
TI  - Characterization of a lysyl aminopeptidase activity associated with
      phosphoglucose isomerase of Vibrio vulnificus.
AB  - Phosphoglucose isomerase (PGI) is a multifunctional enzyme involved in glycolysis
      and gluconeogenesis and, in mammalian cells, functions as neuroleukin, autocrine
      motility factor (AMF), and differentiation and maturation factor (MF). We
      isolated and characterized PGI with a novel lysyl aminopeptidase (LysAP) activity
      (PGI-LysAP) from Vibrio vulnificus. Mass spectrometry revealed that PGI-LysAP is
      a heterodimer consisting of 23.4- and 60.8-kDa subunits. Only the heterodimer
      displayed LysAP activity. PGI-LysAP has a pI around 6.0 and high specificity
      toward the synthetic, fluorogenic substrate l-lysyl-7-amino-4-methylcoumarin.
      LysAP activity is optimal at pH 8.0, is 64% higher at 37 degrees C than at 21
      degrees C, does not directly correlate with virulence, and is strongly inhibited
      by serine protease and metalloprotease inhibitors. PGI-LysAP was also identified
      in Vibrio parahaemolyticus and V. cholerae, but was absent from non-Vibrio human
      pathogens. Sequencing of the pgi gene revealed 1653 bp coding for a 550-amino
      acid protein. Cloned and expressed PGI formed a homodimer with isomerase
      activity, but not LysAP activity. The finding of LysAP activity associated with
      heterodimeric PGI should foster a broad search for putative substrates in an
      effort to elucidate the role of PGI-LysAP in bacteria and its roles in the
      pathophysiology of diseases.

PMID- 15262232
TI  - Translational molecular imaging.

PMID- 15262233
TI  - Positron emission tomography versus positron emission tomography/computed
      tomography: from "unclear" to "new-clear" medicine.
AB  - PET/CT is a new diagnostic imaging modality, which proves that adding PET and CT
      is not merely additive, but highly synergistic. While PET provides high
      sensitivity for lesion detection, CT provides the anatomic backdrop, which
      frequently is important in order to make a specific diagnosis. CT can, however,
      also add sensitivity to PET, as certain lesions such as small clearly
      pathological lung nodules may not at all be visualized on PET alone; and PET
      clearly adds specificity to CT because, e.g., indeterminate lymph nodes seen on
      CT can often be diagnosed unequivocally as benign or malignant, using PET
      information. Furthermore, attenuation correction of PET data, which is needed for
      best PET image quality, can also be obtained using the same CT data. Hence,
      PET/CT also provides a very fast solution for obtaining attenuation images. The
      major clinical applications of PET/CT are in tumor imaging of the body and the
      search for inflammatory foci, while for brain imaging, PET/CT is less relevant.
      In the brain, post acquisition fusion of PET and MRI data is relatively easy,
      while post acquisition fusion of PET and CT or MR data in the body is unreliable
      and cumbersome. We strongly feel that PET/CT is the oncological staging "one-stop
      shop" examination of the future for many tumors. The key question in the next few
      years will be how much CT is needed in PET/CT for which clinical question? The
      advent of ever faster CT scanners suggests that PET/CT eventually may also
      provide a tool for a cardiac "one-stop-shop." So the future of PET/CT indeed
      looks bright.

PMID- 15262234
TI  - Positron emission tomography/computed tomography--imaging protocols, artifacts,
      and pitfalls.
AB  - There has been a longstanding interest in fused images of anatomical information,
      such as that provided by computed tomography (CT) or magnetic resonance imaging
      (MRI) systems, with biological information obtainable by positron emission
      tomography (PET). The near-simultaneous data acquisition in a fixed combination
      of a PET and a CT scanner in a combined PET/CT imaging system minimizes spatial
      and temporal mismatches between the modalities by eliminating the need to move
      the patient in between exams. In addition, using the fast CT scan for PET
      attenuation correction, the duration of the examination is significantly reduced
      compared to standalone PET imaging with standard rod-transmission sources. The
      main source of artifacts arises from the use of the CT-data for scatter and
      attenuation correction of the PET images. Today, CT reconstruction algorithms
      cannot account for the presence of metal implants, such as dental fillings or
      prostheses, properly, thus resulting in streak artifacts, which are propagated
      into the PET image by the attenuation correction. The transformation of
      attenuation coefficients at X-ray energies to those at 511 keV works well for
      soft tissues, bone, and air, but again is insufficient for dense CT contrast
      agents, such as iodine or barium. Finally, mismatches, for example, due to
      uncoordinated respiration result in incorrect attenuation-corrected PET images.
      These artifacts, however, can be minimized or avoided prospectively by careful
      acquisition protocol considerations. In doubt, the uncorrected images almost
      always allow discrimination between true and artificial finding. PET/CT has to be
      integrated into the diagnostic workflow for harvesting the full potential of the
      new modality. In particular, the diagnostic power of both, the CT and the PET
      within the combination must not be underestimated. By combining multiple
      diagnostic studies within a single examination, significant logistic advantages
      can be expected if the combined PET/CT examination is to replace separate state
      of-the-art PET and CT exams, thus resulting in significantly accelerated
      diagnostics.

PMID- 15262235
TI  - The utility of 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography and
      combined positron emission tomography and computed tomography in lymphoma and
      melanoma.
AB  - The purpose of this article is to review the clinical utility of FDG and FDG
      PET/CT imaging in lymphoma and melanoma. A review of the important articles
      supporting the use of FDG PET imaging in the staging, restaging, and monitoring
      of response to therapy in lymphoma and melanoma is provided. The intent is to
      give the nuclear medicine physician and or radiologist the perspective of what
      may be important clinically to make FDG PET imaging an integral part of the
      workup of lymphoma and melanoma patients. Specific clinical scenarios and uptake
      patterns that are unique for lymphoma and melanoma are discussed to ensure
      relevant and proper interpretation of the FDG PET scans. FDG PET scanning in
      summary is a useful imaging modality in the staging, restaging, and response
      evaluation of patients with lymphoma and melanoma.

PMID- 15262236
TI  - Improved imaging and the clinician: the role of positron emission tomography in
      the management of colorectal cancer.
AB  - Colorectal cancer is the second most common cause of cancer death in the United
      States and Western Europe. Positron emission tomography (PET) has been shown to
      be a valuable tool for the evaluation of malignancies of the breast, lung, and
      gastrointestinal tract. Potential areas of utility in patients with colorectal
      cancer include early detection, improved staging at the time of initial
      diagnosis, the detection and staging of recurrent disease, and early
      determination of treatment response. Despite continued advancement in the
      technical aspects of PET, the true measure of its worth is how well it assists
      the clinician in the care of the patient. To best use the information provided by
      PET, the nuclear medicine physician and oncologist must both understand the
      treatment choices available for patients at various stages in the disease.

PMID- 15262237
TI  - Positron emission tomography as a tool for translational research in oncology.
AB  - Growing knowledge of the molecular mechanisms of oncological disease plays a key
      role in the improvement of prevention, diagnosis and treatment of malignant
      tumors. In this review, positron emission tomography (PET) is described as a
      mediator between molecular oncological research and clinical management of tumor
      patients. The most promising applications of PET in the near future include tumor
      imaging with newly developed tracers for diagnosis, staging and grading purposes,
      therapy monitoring with proliferation and apoptosis markers and definition of the
      tumor environment (e.g. hypoxia, neoangiogenesis) prior to therapy. Many of these
      applications will greatly benefit from the use of integrated PET/CT due to its
      precise spatial and morphological assignment of functional information. In
      conclusion, PET is both capable and necessary for the transference of new
      biological knowledge to clinical practice. Thus, PET constitutes a strong basis
      for an advanced and individually tailored approach to tumor patients.

PMID- 15262238
TI  - Positron emission tomography and gene therapy: basic concepts and experimental
      approaches for in vivo gene expression imaging.
AB  - More than two decades of intense research have allowed gene therapy to move from
      the laboratory to the clinical setting, where its use for the treatment of human
      pathologies has been considerably increased in the last years. However, many
      crucial questions remain to be solved in this challenging field. In vivo imaging
      with positron emission tomography (PET) by combination of the appropriate PET
      reporter gene and PET reporter probe could provide invaluable qualitative and
      quantitative information to answer multiple unsolved questions about gene
      therapy. PET imaging could be used to define parameters not available by other
      techniques that are of substantial interest not only for the proper understanding
      of the gene therapy process, but also for its future development and clinical
      application in humans. This review focuses on the molecular biology basis of gene
      therapy and molecular imaging, describing the fundamentals of in vivo gene
      expression imaging by PET, and the application of PET to gene therapy, as a
      technology that can be used in many different ways. It could be applied to avoid
      invasive procedures for gene therapy monitoring; accurately diagnose the
      pathology for better planning of the most adequate therapeutic approach; as
      treatment evaluation to image the functional effects of gene therapy at the
      biochemical level; as a quantitative noninvasive way to monitor the location,
      magnitude and persistence of gene expression over time; and would also help to a
      better understanding of vector biology and pharmacology devoted to the
      development of safer and more efficient vectors.

PMID- 15262239
TI  - Positron emission tomography in clinical neurology.
AB  - Positron emission tomography (PET) imaging in clinical neurology serves several
      purposes: differential diagnosis, especially in the early stage of neurologic
      disorders, description of pathophysiologic changes that are responsible for
      manifestation and course of a disease, and evaluation and follow-up of treatment
      effects. Many of these applications are possible with the most widely available
      PET tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Additional tracers are used
      clinically to detect the disturbance of specific neurotransmitter and receptor
      systems, blood flow, oxygen metabolism, and amino acid uptake. Main diagnostic
      issues addressed in this review are early diagnosis of Alzheimer's disease and
      other dementias, differential diagnosis of movement disorders, diagnosis of
      recurrent brain tumors, identification of viable tissue in ischemic stroke, and
      localization of epileptogenic foci. Techniques for presurgical localization of
      eloquent cortex and monitoring of therapy are presented.

PMID- 15262240
TI  - Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS
      5 in primary bovine articular chondrocyte pellet culture system.
AB  - INTRODUCTION: Articular cartilage matrix synthesis and degradation are dynamic
      processes that must be balanced for proper maintenance of the tissue. In
      osteoarthritis (OA), this balance is skewed toward degradation and ultimate loss
      of matrix. The transcriptional and/or activity levels of hundreds of genes are
      dysregulated in chondrocytes from osteoarthritic cartilage, and a subset of these
      genes may represent pivotal factors that could be modulated if their specific
      role in the disease process could be identified. OBJECTIVE: To investigate the
      role of ADAMTS-4 and ADAMTS-5 in cartilage matrix degradation by developing a
      chondrocyte pellet culture assay in combination with adenoviral gene expression,
      and to demonstrate the utility of this assay by assessing the specific functional
      contribution of these genes to cartilage matrix metabolism. METHODS: A full
      length cDNA for bovine ADAMTS-4 (bADAMTS-4) was isolated, and used to evaluate
      the expression, regulation, and activity of this gene in bovine cartilage.
      Adenoviruses expressing bADAMTS-4, human ADAMTS-5 (hADAMTS-5) or human bone
      morphogenetic protein 2 (BMP-2) were used to infect primary chondrocytes, and
      their effect on extracellular matrix metabolism was assessed by monitoring the
      accumulation and release of glycosaminoglycans (GAG) in three-dimensional
      chondrocyte pellet cultures. RESULTS: Analysis of bADAMTS-4 transcriptional
      regulation in chondrocytes revealed that interleukin-1alpha (IL-1alpha) was the
      most potent inducer of bADAMTS-4 mRNA and subsequent aggrecan degradation in
      cartilage explant cultures of those cytokines tested. bADAMTS-4 mRNA induction by
      IL-1alpha was greater in nasal cartilage than in articular cartilage.
      Chondrocytes infected with adenovirus expressing either bADAMTS-4 or hADAMTS-5
      genes showed increased aggrecan degradation in newly synthesized matrix by pellet
      cultures while chondrocytes overexpressing BMP-2 showed increased aggrecan
      synthesis. CONCLUSION: Adenoviral delivery of genes to primary bovine
      chondrocytes, followed by culture in three-dimensional pellet format and
      evaluation of extracellular matrix protein metabolism, is a useful functional
      assay for assessing the role of genes on cartilage matrix synthesis and
      degradation.

PMID- 15262241
TI  - High-resolution MRI and micro-CT in an ex vivo rabbit anterior cruciate ligament
      transection model of osteoarthritis.
AB  - OBJECTIVE: The aim of this study was to investigate the potential of using non
      invasive, multi-modality imaging techniques to quantify disease progression in a
      rabbit model of experimentally induced osteoarthritis (OA). METHODS: High
      resolution 4-T magnetic resonance imaging (MRI) and micro-computed tomography
      (micro-CT) techniques were implemented and validated in an ex vivo rabbit
      anterior cruciate ligament transection (ACLT) model of OA. A three-dimensional (3
      D) rigid body registration technique was executed and evaluated to allow combined
      MR-CT analysis in co-registered image volumes of the knee. RESULTS: The 3-D MRI
      and micro-CT data formats made it possible to quantify cartilage damage, joint
      space, and osseous changes in the rabbit ACLT model of OA. Spoiled gradient
      recalled echo and fast-spin echo (FSE) sequences were jointly used to evaluate
      femorotibial cartilage and determine the sensitivity (78.3%) and specificity
      (95.3%) of 4-T MRI to detect clinically significant cartilage lesions. Overall
      precision error of the micro-CT technique for analysis of joint-space, volumetric
      bone mineral density (vBMD), and bone volume fraction (BV/TV) was 1.8%, 1.2%, and
      2.0%, respectively. Co-registration of the 3-D data sets was achieved to within
      0.36 mm for completed intermodality registrations, 0.22 mm for extrapolated
      intramodality registrations, and 0.50mm for extrapolated intermodality
      registrations. CONCLUSIONS: These results indicate that high-resolution 4-T MRI
      and micro-CT can be used to accurately quantify cartilage damage and calcified
      tissue changes in the rabbit ACLT model of OA. In addition, image volumes can be
      successfully co-registered to facilitate a comprehensive multi-modality
      examination of localized changes in both soft tissue and bone within the rabbit
      femorotibial joint.

PMID- 15262242
TI  - Synovial lining macrophages mediate osteophyte formation during experimental
      osteoarthritis.
AB  - OBJECTIVE: In human osteoarthritis (OA), various forms of pathology are observed.
      Besides cartilage damage and fibrosis, neogenesis of bone, osteophyte formation,
      also occurs. Osteophytes are thought to limit joint movement and cause pain. The
      objective of this study was to investigate whether synovial macrophages are
      involved in osteophyte formation in experimental OA, and if they are, to study
      which mechanism may be involved. DESIGN: Experimental OA was induced by two intra
      articular injections of collagenase on alternate days into murine knee joints.
      The role of synovial lining macrophages in this model was studied by selective
      removal of these cells prior to OA induction using clodronate liposomes. After 1
      and 2 weeks, knee joints were dissected and examined (immuno)histologically.
      RESULTS: At days 7 and 14 after induction of OA, osteophyte formation and
      fibrosis were observed. Depletion of synovial macrophages resulted in spectacular
      reduction of osteophyte formation, 84% and 66%, respectively, at days 7 and 14.
      Fibrosis and synovial activation, measured by MRP8/14 expression, were also
      ameliorated (40-60%). In addition, production of growth factors (TGFbeta, BMP-2
      and BMP-4) in the lining was largely prevented but production of these growth
      factors in deeper layers of the synovium and the periosteum did not differ from
      controls. CONCLUSIONS: These results indicate the synovial macrophage to be a
      pivotal cell in the synovium mediating osteophyte formation and other OA-related
      pathology, like fibrosis, during experimental OA. Production of growth factors
      and induction of synovial activation by these cells may play a crucial role in
      this event.

PMID- 15262243
TI  - Fibroblast growth factor-2 promotes the repair of partial thickness defects of
      articular cartilage in immature rabbits but not in mature rabbits.
AB  - OBJECTIVE: To investigate cartilage response to fibroblast growth factor-2 (FGF
      2) with increasing age in vivo, we examined the effect of FGF-2 on partial
      thickness defects of immature and mature rabbits. DESIGN: Sixty-nine Japanese
      white rabbits (34 immature rabbits, 35 mature rabbits) were examined. We made
      experimental partial thickness defects in articular cartilage of the knees. Then,
      we injected FGF-2 into the knees eight times, immediately after surgery and every
      2 days for 2 weeks. A single dose of FGF-2 was 10 ng/0.1 ml or 100 ng/0.1 ml. In
      the control group, 0.1 ml saline was injected on the same time schedule. The
      rabbits were sacrificed at intervals following surgery that ranged from 2 to 48
      weeks. The specimens were stained with toluidine blue and examined
      microscopically. We used a modified semiquantitative scale for evaluating the
      histological appearance of repair. RESULTS: In immature rabbits, the cartilage
      repair in the FGF-2 (100 ng)-treated group was significantly better than that of
      the other groups. The defects were almost completely repaired with chondrocytes
      that showed a round to polygonal morphology, and large amounts of extracellular
      matrix with intense metachromatic staining. In mature rabbits, however, there was
      apparently no effect from FGF-2 in either group. CONCLUSIONS: Application of FGF
      2 facilitated cartilage repair in partial thickness defects in immature rabbits,
      but not in mature ones.

PMID- 15262244
TI  - Efficacy and safety of a single intra-articular injection of non-animal
      stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee.
AB  - OBJECTIVE: Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan
      (HA) preparation with a 4-week intra-articular half-life. This study compared the
      efficacy of a single injection of NASHA with placebo in patients with
      osteoarthritis (OA) of the knee. DESIGN: This was a 26-week randomized, double
      blind, multicenter study of a single intra-articular knee injection with either
      NASHA or placebo (saline). Assessments included the Western Ontario McMasters
      Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall
      global disease status. A positive response was defined as a reduction in WOMAC
      pain score for the study knee of 40% from baseline with a minimum improvement of
      > or =5 points. RESULTS: A total of 346 (NASHA 172; placebo 174) patients were
      treated. WOMAC scores and quality of life were improved in both the NASHA and
      placebo groups. For the overall population, there were no statistically
      significant between-group differences in response rates for any efficacy
      parameters. In patients with OA confined to the knee (N=216), a greater response
      to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment
      related events. CONCLUSIONS: NASHA was not superior to placebo for the primary
      efficacy analysis. However, these data may be confounded by the inclusion of
      patients with OA at other sites, as significant benefits over placebo were found
      among patients with OA confined to the knee. Future trials of OA that examine a
      local therapy might need to consider restricting the study population to those
      patients having OA of only the signal joint.

PMID- 15262245
TI  - Three-dimensional distribution of acetabular cartilage thickness in patients with
      hip dysplasia: a fully automated computational analysis of MR imaging.
AB  - OBJECTIVE: The aim of this study was to evaluate three-dimensional (3D)
      distribution of acetabular articular cartilage thickness in patients with hip
      dysplasia using in vivo magnetic resonance (MR) imaging, and to compare cartilage
      thickness distribution between normal and dysplastic hips. DESIGN: Forty-five
      dysplastic hips without joint space narrowing on radiographs and 13 normal hips
      underwent MR imaging with fat-suppressed 3D fast spoiled gradient echo (SPGR)
      sequence. Acetabular cartilage thickness was measured with a fully automated
      segmentation technique, and cartilage thickness distribution was compared between
      the dysplastic and normal hips on the celestial spherical coordinate system.
      RESULTS: Average cartilage thickness was significantly greater for the dysplastic
      hips than the normal hips (1.77 mm vs 1.34 mm). There was a general trend of
      gradient increase of cartilage thickness at the superolateral area in normal and
      dysplastic hips. The gradient increase of cartilage thickness was significantly
      greater in the dysplastic hips than the normal hips. CONCLUSIONS: Dysplastic hips
      have general thick cartilage distribution as well as more prominent gradient
      increase of thickness at the superolateral portion. The knowledge of fundamental
      morphological feature of dysplastic hips at a preradiologic stage may aid early
      detection of cartilage thinning in association with osteoarthritic progression,
      accurate computational biomechanical analysis in the hip joint, and planning
      periacetabular osteotomy with satisfactory cartilaginous congruency.

PMID- 15262246
TI  - Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis
      tissue in primary osteoarthritis in vitro.
AB  - OBJECTIVES: To investigate the relative contribution of the cyclooxygenase (COX)
      isoenzymes COX-1 and COX-2 to prostaglandin E2 (PGE2) release from inflamed
      synovial tissue in N=10 patients with primary osteoarthritis (OA) in vitro and to
      determine possible effects of COX inhibitors on the gene expression of synovial
      COX-1 and COX-2. DESIGN: The effects of a COX-unspecific nonsteroidal anti
      inflammatory drug (NSAID; diclofenac), a selective COX-1 inhibitor (SC-560) and a
      selective COX-2 inhibitor (SC-58125) on PGE2 release from inflamed synovial
      tissue (0.1-10 microM, 3 and 6 h incubation time) were compared. Release of PGE2
      into the incubation media was measured by means of the enzyme-linked
      immunosorbent assay. Expression of synovial COX-1/-2 was quantified by means of
      real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: All
      agents inhibited synovial PGE2 release dose-dependently. Compared to short-term
      incubations, the inhibitory potency of diclofenac, SC-58125 and SC-560 was
      increased (0.1-10 microM) and decreased (0.1-1 microM), respectively, during 6 h:
      At 10 microM, SC-560 and SC-58125 had obviously lost their specificity for COX-1
      and COX-2, respectively, indicated by a comparable inhibitory potency of the
      selective COX-1 inhibitor (86.6%) and the selective COX-2 inhibitor (96.6%)
      within identical tissue specimens. In contrast, at 1 microM, 83% and 62.8%
      inhibition was seen for diclofenac and SC-58125, respectively. SC-560 showed
      30.6% inhibition (P<0.05). In contrast to synovial COX-1, RT-PCR revealed a
      significant induction of COX-2 through PGE2. CONCLUSIONS: With respect to the
      concentrations studied, the data suggest that in inflamed synovial tissue in OA,
      up to 30% of PGE2 might be generated via the COX-1 pathway. In therapy of OA, the
      relative contribution of COX-1 in synovial inflammation should be considered,
      weighing the potency of COX-unspecific NSAID against the assumed superior
      gastrointestinal safety profile of selective COX-2 inhibitors.

PMID- 15262247
TI  - Biomechanical, histologic and macroscopic assessment of articular cartilage in a
      sheep model of osteoarthritis.
AB  - OBJECTIVES: Our primary objective was to explore the full potential of the ovine
      medial meniscectomy (MMx) model of early osteoarthritis (OA) for studies to
      validate non-destructive articular cartilage (AC) assessments and therapeutic
      interventions. Our secondary objective was to re-evaluate the relationships
      between the different types of AC assessment after MMx in sheep. METHODS:
      Macroscopic assessments, dynamic shear modulus (G*), phase lag and AC thickness
      measurements were performed at a total of 5437 reference points on all six
      articular surfaces in four normal joints and 16 MMx ovine stifle (knee) joints.
      Comparisons with histologic assessments of gross structural damage, collagen
      organisation (birefringence) and proteoglycan content were possible at 702 of
      these points. RESULTS: Histologic gross structural damage and proteoglycan loss
      were seen throughout the joint with greatest severity (fibrillation) in closest
      proximity to the MMx site. Increases in AC (30-50%) thickness, reductions in G*
      (30-40%) and collagen birefringence intensity (15-30%) occurred more evenly
      throughout the joint. Macroscopic softening was evident only when G* declined by
      80%. G* correlated with AC thickness (rho=-0.47), collagen organisation
      rho=0.44), gross structural damage (rho=-0.44) and proteoglycan content
      (rho=0.42). Multivariate analysis showed that collagen organisation contributed
      twice as much to dynamic shear modulus (t=6.66 as proteoglycan content (t=3.21).
      Collagen organisation (rho=0.11) and proteoglycan content (rho=0.09) correlated
      only weakly to phase lag. CONCLUSIONS: Macroscopic assessments were insensitive
      to AC softening suggesting that arthroscopic assessments of AC status might also
      perform poorly. Collagen integrity was more important for the maintenance of AC
      stiffness (G*) than proteoglycan content. The development of major AC softening
      and thickening throughout the joint following MMx suggested involvement of non
      mechanical (e.g., protein and biochemical) chemical and cytokine mediated
      processes in addition to the disturbance in biomechanical loading. The ovine MMx
      model provides a setting in which the spectrum of AC changes associated with the
      initiation and progression of OA may be evaluated.

PMID- 15262248
TI  - An in-vivo experimental model for studying wound-healing after laser irradiation
      in the mouse foetus.
AB  - OBJECTIVE: The purpose of this study was to develop an experimental model to
      study wound-healing in the mouse foetus by inducing an injury with an argon
      laser. MATERIAL AND METHODS: ICR strain mouse dams were used in this study at day
      14 of gestation. Laparotomy was performed on the dams under sodium pentobarbital
      anaesthesia, and foetuses were exposed from the uterus while wrapped in the
      amnion. Laser radiation was conducted through the amniotic membrane, and the beam
      was focused on to the naso-labial region. After laser irradiation, the foetus was
      returned to the abdominal cavity of the dam. Then the abdominal wall was closed,
      and an extrauterine pregnancy was maintained. Foetuses were sacrificed at
      intervals and wound healing was examined histologically. RESULTS: Immediately
      after laser irradiation, the foetal epithelium was detached and degeneration of
      the epithelium and subepithelial mesenchymal tissue were observed. Twenty-four
      hours after laser irradiation, normal epithelial cells surrounding the wound
      began to migrate along the margin of the degenerate tissue mass. By seventy-two
      hours after laser irradiation, the laser-induced wound had recovered, and scar
      formation was not observed. CONCLUSION: The application of an argon laser allowed
      to inflict a wound on a mouse foetus without damaging the amnion, and this
      experimental model appeared to be useful for studying the mechanism of foetal
      wound-healing.

PMID- 15262249
TI  - Intrauterine autogenous foetal bone transplantation for the repair of cleft-like
      defects in the mid-gestational sheep model.
AB  - AIM: The success of intrauterine surgery in treating non-life-threatening
      malformations such as myelomeningocoele, has also renewed strong interest in
      using this technique for treating craniofacial malformations. Nevertheless, the
      only experimental cleft-like defect models known, are those concerning wound
      healing of soft tissues. MATERIAL AND METHODS: Attempts were made to repair
      artificial cleft-like defects including transplantation of 11 autogenous foetal
      bone grafts from the iliac crest or ulna, and were randomly assigned to three
      study groups, using the mid-gestational sheep model. In a 4th study group,
      lyophilized collagen, a bone-regenerating bioresorbable implant material, was
      used to fill the alveolar defect. RESULTS: In all groups, there was a slight
      degree of asymmetry and thinning of the lip. Radiological studies demonstrated a
      variable degree of abnormality of the maxilla, ranging from none to a mild
      deviation. Three-dimensional computer tomography, two-dimensional maximal
      intensity projection findings, and histological analysis confirmed bony healing
      of the alveolar cleft-like defect. DISCUSSION/CONCLUSION: Intrauterine autogenous
      foetal bone transplantation for the repair of cleft-like defects in the sheep is
      feasible. This is a reliable and valuable model toward a possible clinical
      application for intrauterine treatment of clefts.

PMID- 15262250
TI  - Microstructured dental implants and palatal mucosal grafts in cleft patients: a
      retrospective analysis.
AB  - BACKGROUND: In cleft patients, implant dentistry has become an integral part of
      oral rehabilitation. However, a lack of keratinized mucosa is found in many cases
      which may have adverse effects on the long-term success of dental implants with
      microstructured surfaces. Therefore, the aim of this study was to evaluate
      whether mucogingival surgery is of value in the treatment of these patients.
      PATIENTS: Between 1991 and 2002, a total of 35 microstructured dental implants
      were inserted in 32 cleft patients. In 18 patients, vestibular scars extended to
      the rim of the marginal mucosa of the implants and the gingiva of the adjacent
      teeth. To enhance the soft tissue condition, mucogingival surgery was performed
      using palatal mucosal grafts. METHODS: In May 2002, 29 implants and 16 mucosal
      grafts were evaluated. Assessment included radiological and clinical parameters.
      RESULTS: Three implants were lost. Most mucosal grafts showed shrinkage of up to
      30%. Clinical and radiological parameters, however, showed results that were very
      similar to those from non-cleft patients. CONCLUSION: These results support the
      hypothesis that keratinized mucosal grafts show long-term success in the cleft
      region as well. Moreover, it may be concluded that a combination of dental
      implants with a rough surface and palatal mucosal grafts can be recommended for
      oral rehabilitation of cleft patients.

PMID- 15262251
TI  - Investigation of caries prevalence in children with cleft lip, alveolus, and
      palate.
AB  - AIM: The purpose of this study was to assess the prevalence of dental caries in
      children with orofacial clefts. PATIENTS: A total of 623 children aged 6-16 years
      with cleft lip, alveolus, and palate were included in the study. They were
      compared with 47,646 schoolchildren from Leipzig (Germany). METHODS: This cross
      sectional study used the standard dental indices dmf(t) and DMF(T) for clinical
      assessment. Children underwent a dental examination under standard conditions of
      seating and lighting in the out-patient department of paediatric dentistry as
      part of a regular checkup. RESULTS: The prevalence of caries was significantly
      higher in children with cleft lip, alveolus, and palate in permanent and
      deciduous teeth. CONCLUSION: These assessments not only provide a baseline for
      oral health parameters in young patients with clefts, but also underline the need
      for a more aggressive approach to the prevention of oral disease to optimize
      clinical outcome.

PMID- 15262252
TI  - Scoliosis of the cranial base: radiological and mathematical analysis using
      finite elements system analysis (FESA) of a case.
AB  - INTRODUCTION AND PROPOSED STUDY: Numerous deforming syndromes of the craniofacial
      complex involve also the symmetry of the cranial base. This study considers a
      particular alteration, that of 'scoliosis', in which the line Nasion-Sella-Basion
      Inion is not rectilinear but curved, due to a torsion of the cranial base in the
      horizontal plane. MATERIALS: Plagiocephaly was studied in one patient, which was
      probably caused by altered timing or mechanism of closure of the cranial sutures.
      METHODS: This study was carried out using CT images of the patient's craniofacial
      complex, using standard neuroradiological points. In order to study the forces
      that operated in the various complexes, a mathematical analysis was applied
      namely, a finite element system analysis (FESA). RESULTS: From this mathematical
      study, which has enabled us to evaluate the forces that operate in determining
      the deformity, it has been possible to locate two sites of force concentration.
      They were located at different levels and on opposite sides. CONCLUSION: This
      finding could explain why the middle and lower thirds of the face were also
      involved.

PMID- 15262253
TI  - Mucinous intestinal type adenocarcinoma of the sinonasal tract secondary to
      passive wood dust inhalation: case report.
AB  - A 76-year-old female patient with a mucinous intestinal type adenocarcinoma of
      the sinonasal tract is described. The probable aetiology of passive hard wood
      dust inhalation, investigations carried out and subsequent surgical treatment
      using a transfacial access approach and a temporoparietal fascial composite free
      flap in conjunction with free auricular cartilage are described.

PMID- 15262254
TI  - Cephalometric long-term follow-up of nasal augmentation using iliac bone graft.
AB  - INTRODUCTION: Iliac bone grafts for nasal augmentation are characterized by
      resorption. In this article, the relationship between graft resorption and soft
      tissue retrusion is examined by cephalogram-based measurements. METHODS: Ten
      patients with nasal deformity underwent iliac bone grafts to the nose and were
      monitored using cephalograms at intervals. On every image, three distances were
      measured; the tip height and the upper and lower lengths of the graft. RESULTS:
      The upper length of the grafted bone reached 90% stability after 6 months, and
      the lower length reached 70% stability between 1 and 2 years postoperatively. At
      the tip, supported by the lower part of the grafted bone, the soft tissue
      projection reached 90% stability after 6 months. DISCUSSION: The lower part of
      the iliac bone grafted onto the nasal dorsum supports the projecting soft tissue
      of the nasal tip. Thus subsequent resorption of the graft results in retrusion of
      the nasal tip. However, the degree of soft tissue retrusion was obviously less
      than the amount by which the supporting bone resorbed. It seems likely that the
      augmentation effect persists due to the formation of scar tissue.

PMID- 15262255
TI  - Treatment of temporomandibular joint ankylosis by a modified fossa prosthesis.
AB  - BACKGROUND AND OBJECTIVE: Treatment of temporomandibular joint ankylosis is a
      challenge and suffers from a high incidence of recurrence. Although treatment of
      ankylosis has been tried as early as nearly 200 years ago, no single technique
      produced satisfactory results. An alternative technique and a modified spacer
      system are described in this paper. MATERIAL AND METHODS: Fifteen patients, nine
      of whom had unilateral and the remaining six had bilateral ankylosis were
      evaluated. Modified fossa implants were used in all cases. RESULTS: The highest
      incidence of ankylosis was observed in the 11-20 year age group (nine patients).
      Falls during childhood was the common aetiological factor. Eight patients had
      been previously operated upon. Postoperative interinsicial opening values were
      remarkably different from the preoperative ones and the long-term results were
      satisfactory. CONCLUSION: With continued research and development in the
      treatment of ankylosis, temporomandibular joint implants will become more
      predictable and reliable. This specially designed fossa implant seems to be
      promising in the treatment of TMJ ankylosis.

PMID- 15262256
TI  - Modifications of the inverted T-shaped silicone implant for treatment of
      temporomandibular joint ankylosis.
AB  - PURPOSE: Inverted T-shaped silicone implants have been used for reconstruction of
      ankylosed temporomandibular joints for 10 years. As the implant is custom made
      during the operation, dimensional adjustments according to individual need are
      routine. MATERIAL AND METHOD: A new modification to increase the stability of the
      inverted T-shaped silicone implant is presented. The modification consists of a
      middle process on the long arm of the T-shaped silicone implant, the first of
      which was inserted into the medullary cavity of the mandibular ramus. This
      modification further stabilizes the implant position and helps prevent its
      displacement. The modification was used on difficult cases such as bilateral
      ankylosis, osteotomies below the condylar notch or incompliant patients. This
      modification was used in six patients. RESULTS: No dislocation, nor extrusion of
      the implant or re-ankylosis of TMJ was observed.

PMID- 15262257
TI  - Immunohistochemical long-term evaluation of laminin expression in microvascular
      anastomoses of the carotid artery in the Wistar rat.
AB  - INTRODUCTION: The main risk of complications of free-flap tissue transfer is from
      the microvascular anastomoses. The anastomoses are threatened by thrombosis,
      aneurysm and vascular insufficiency. Laminin is associated with the basement
      membrane complex and plays an essential role in vascular tissue organization,
      wound healing and supports mechanical properties of vessels. A long-term animal
      experiment was used to obtain new information on the distribution of laminin in
      anastomoses. METHODS: Seventy Wistar rats, seven groups of 10 animals each, were
      operated upon. A 4mm long segment of common carotid artery was removed and
      reinserted. After various periods (from directly postoperative to 6 months
      later), the common carotid arteries, including the bifurcation, were isolated
      after cardiovascular perfusion. Carotid arteries were embedded and cross-sections
      stained using an immunohistochemical anti-laminin-antibody. Two anastomoses with
      four sutures each were examined by using this technique to evaluate
      histomorphology and intensity of anti-laminin staining. RESULTS: Compression,
      shift and dehiscence were often seen following vessel apposition. A loss of
      laminin expression was observed in the media in cases of compression and shift
      after 6 months. The grade of expression of laminin in anastomoses was dependent
      on the extent of injury. CONCLUSIONS: The application of antibodies to identify
      the laminin distribution was valuable for studying vascular healing. A well
      performed microvascular anastomosis is clinically important not only for the
      acute phase following the operation, but also long term. Further antibody studies
      could be used in follow-up studies of vascular prostheses.

PMID- 15262258
TI  - Oral mucosal melanoma: a series of case reports.
AB  - INTRODUCTION: Due to the rarity of oral malignant melanomas case reports are a
      necessary source of information. Ten new cases are reported with a minimum follow
      up of 3 years. PATIENTS AND METHODS: Patients were treated during a period of 10
      years. Clinical, demographic and pathologic findings were examined. RESULTS: In 6
      males (60%) and 4 females with a mean age of 64.3 years the tumour locations
      were: hard palate-maxillary gingiva (3 cases), maxillary gingiva (2), lower
      gingiva (2), tongue (2), hard/soft palate-buccal mucosa (1). Pre-existing
      melanotic pigmentation had been present in 4 patients. Four patients were in
      stage I, 5 in stage II, and 1 in stage III. Surgical excision was the primary
      treatment in 9 cases. Five patients underwent simultaneous neck dissections. All
      patients received radiation and multimode adjuvant therapies. After a 3-year
      follow-up 3 patients are still alive (50% (2/4) of those presenting in stage I
      and 20% (1/5) in stage II). CONCLUSIONS: Due to the rarity of oral melanoma,
      individual experience is limited. The poor prognosis and the different treatments
      reflect this situation.

PMID- 15262259
TI  - Amyloid beta protein impairs motor function via thromboxane A2 in the rat
      striatum.
AB  - Amyloid beta protein (Abeta) deposits are found in the striatum of patients with
      Alzheimer disease (AD) showing extrapyramidal motor dysfunction, but neuronal
      cell loss has not yet been detected. To clarify how Abeta impairs motor function,
      we analyzed intrastriatally Abeta-injected rats. Unilateral injection of Abeta(25
      35) enhanced apomorphine-induced circling in an ipsilateral direction, indicating
      ipsilateral dysfunction of dopaminergic nigrostriatal pathways. Volumes of lesion
      in the Abeta(25-35)-injected striata were significantly higher than those in the
      saline-injected ones. The correlation between lesion volume and circling behavior
      was close to significance, but slightly too low, suggesting the possible
      involvement of other factors in the striatal dysfunction. Abeta(25-35)
      significantly elevated the level of thromboxane A2 (TXA2). A stable TXA2 agonist,
      U46619, enhanced circling behavior, and TXA2 receptor antagonists attenuated
      U46619- and Abeta(25-35)-enhanced circling behavior. This study demonstrated that
      Abeta(25-35) impairs the motor function of dopaminergic neurons via neuronal cell
      loss and TXA2. It also sheds light on the therapeutic potential of TXA2 receptor
      blockers for the neurotoxicity of Abeta.

PMID- 15262260
TI  - Uridine release during aminopyridine-induced epilepsy.
AB  - Uridine, like adenosine, is released under sustained depolarization and it can
      inhibit hippocampal neuronal activity, suggesting that uridine may be released
      during seizures and can be involved in epileptic mechanisms. In an in vivo
      microdialysis study, we measured the extracellular changes of nucleoside and
      amino acid levels and recorded cortical EEG during 3-aminopyridine-induced
      epilepsy. Applying silver impregnation and immunohistochemistry, we examined the
      degree of hippocampal cell loss. We found that extracellular concentration of
      uridine, adenosine, inosine, and glutamate increased significantly, while
      glutamine level decreased during seizures. The release of uridine correlated with
      seizure activity. Systemic and local uridine application was ineffective. The
      number of parvalbumin- and calretinin-containing interneurons of dorsal
      hippocampi decreased. We conclude that uridine is released during epileptic
      activity, and suggest that as a neuromodulator, uridine may contribute to
      epilepsy-related neuronal activity changes, but uridine analogues having slower
      turnover would be needed for further investigation of physiological role of
      uridine.

PMID- 15262261
TI  - Hypothalamic activation after stimulation of the superior sagittal sinus in the
      cat: a Fos study.
AB  - Clinical observations, particularly of the premonitory phase of migraine, suggest
      the involvement of the hypothalamus in the earliest phases of an attack.
      Stimulation of the superior sagittal sinus (SSS) in humans produces head pain and
      permits study of the activated trigeminovascular system in experimental settings.
      The distribution of neurons expressing the protein product (Fos) of the c-fos
      immediate early gene was examined in the hypothalamus of anaesthetised (alpha
      chloralose) cats. Animals were studied after either 2-h stimulation of the SSS or
      sham stimulation. Fos protein was detected using immunohistochemistry, and
      positive neurons were plotted onto standardised templates and counted by a
      blinded observer. In response to electrical stimulation of the superior sagittal
      sinus, we found significant activation of the supra-optic nucleus (SON) rising
      from 3 (0-13) (median, 95% confidence interval) to 53 (31-78; P = 0.005) fos
      positive cells. In the posterior hypothalamic area (Hp), fos-positive cells rose
      from 4 (0-14) to 35 (17-45; P = 0.015) Taken together with other physiological
      studies, the data are consistent with a role for hypothalamic structures in the
      modulation of trigeminovascular nociceptive afferent information, and thus for a
      role in headache.

PMID- 15262262
TI  - Improved outcome of N-butyldeoxygalactonojirimycin-mediated substrate reduction
      therapy in a mouse model of Sandhoff disease.
AB  - Sandhoff disease is a severe neurodegenerative glycosphingolipid (GSL) lysosomal
      storage disorder, currently without treatment options. One therapeutic approach
      under investigation is substrate reduction therapy (SRT). By partially inhibiting
      GSL biosynthesis, the impaired rate of GSL catabolism is balanced by a slower
      rate of influx of GSLs into the lysosome. In a previous study, we reported the
      beneficial effects of treating Sandhoff disease mice with the glucose analogue N
      butyldeoxynojirimycin (NB-DNJ), a compound that inhibits the first step of GSL
      biosynthesis catalysed by the ceramide specific glucosyltransferase. NB-DNJ,
      however, exhibits adverse effects at high doses such as weight loss and GI tract
      distress (due to glucosidase inhibition). This might limit the therapeutic
      potential of NB-DNJ for treating diseases affecting the CNS where high dose
      therapy may be required to achieve therapeutic levels of the drug in the brain.
      In the present study, a more selective compound, the galactose analogue N
      butyldeoxygalactonojirimycin (NB-DGJ), was evaluated in the Sandhoff disease
      mouse model. Treatment with NB-DGJ showed greater therapeutic efficacy than NB
      DNJ with no detectable side effects. The ability to escalate the dose of NB-DGJ,
      leading to extended life expectancy and increased delay in symptom onset,
      demonstrates the greater therapeutic potential of NB-DGJ for the treatment of the
      human gangliosidoses.

PMID- 15262263
TI  - Olfactory ensheathing cell transplantation restores functional deficits in rat
      model of Parkinson's disease: a cotransplantation approach with fetal ventral
      mesencephalic cells.
AB  - Different strategies have been worked out to promote survival of transplanted
      fetal ventral mesencephalic cells (VMCs) using trophic and nontrophic support.
      Olfactory ensheathing cells (OECs) express high level of growth factors including
      NGF, bFGF, GDNF, and NT3, which are known to play important role in functional
      restoration or neurodegeneration. In the present investigation, an attempt has
      been made to study functional restoration in 6-hydroxydopamine (6-OHDA)-lesioned
      rat model of Parkinson's disease (PD) following cotransplantation of VMC and OECs
      (cultured from olfactory bulb, OB) in striatal region. The functional restoration
      was assessed using neurobehavioral, neurochemical, and immunohistochemical
      approach. At 12 weeks, post-transplantation, a significant recovery (P < 0.001)
      in D-amphetamine induced circling behavior (73%), and spontaneous locomotor
      activity (SLA, 81%) was evident in cotransplanted animals when compared with 6
      OHDA-lesioned animals. A significant restoration (P < 0.001) in [3H]-spiperone
      binding (77%), dopamine (DA) (82%) and 3,4-dihydroxy phenyl acetic acid (DOPAC)
      level (75%) was observed in animals cotransplanted with OECs and VMC in
      comparison to lesioned animals. A significantly high expression and
      quantification of tyrosine hydroxylase (TH)-positive cells in cotransplanted
      animals further confirmed the supportive role of OECs in viability of
      transplanted dopaminergic cells, which in turn may be helping in functional
      restoration. This was further substantiated by our observation of enhanced TH
      immunoreactivity and differentiation in VMC cocultured with OECs under in vitro
      conditions as compared to VMC alone cultures. The results suggest that
      cotransplantation of OECs and VMC may be a better approach for functional
      restoration in 6-OHDA-induced rat model of Parkinson's disease.

PMID- 15262264
TI  - GFP-tagged prion protein is correctly localized and functionally active in the
      brains of transgenic mice.
AB  - Prion diseases result from conversion of PrPC, a neuronal membrane glycoprotein
      of unknown function, into PrPSc, an abnormal conformer that is thought to be
      infectious. To facilitate analysis of PrP distribution in the brain, we have
      generated transgenic mice in which a PrP promoter drives expression of PrP-EGFP,
      a fusion protein consisting of enhanced green fluorescent protein inserted
      adjacent to the glycolipid attachment site of PrP. We find that PrP-EGFP in the
      brain is glycosylated and glycolipid-anchored and is localized to the surface
      membrane and the Golgi apparatus of neurons. Like endogenous PrP, PrP-EGFP is
      concentrated in synapse-rich regions and along axon tracts. PrP-EGFP is
      functional in vivo, since it ameliorates the cerebellar neurodegeneration induced
      by a truncated form of PrP. These observations clarify uncertainties in the
      cellular localization of PrPC in brain, and they establish PrP-EGFP transgenic
      mice as useful models for further studies of prion biology.

PMID- 15262265
TI  - Zinc release contributes to hypoglycemia-induced neuronal death.
AB  - Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP
      1), an enzyme that normally participates in DNA repair but promotes cell death
      when extensively activated. Endogenous, vesicular zinc in brain is released to
      the extracellular space under conditions causing neuronal depolarization. Here,
      we used a rat model of insulin-induced hypoglycemia to assess the role of zinc
      release in PARP-1 activation and neuronal death after severe hypoglycemia. Zinc
      staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed
      depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals
      and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe
      hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium
      ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and
      significantly reduced hypoglycemia-induced neuronal death. CaEDTA also attenuated
      the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in
      hippocampal neurons. These results suggest that zinc translocation is an
      intermediary step linking hypoglycemia to PARP-1 activation and neuronal death.

PMID- 15262266
TI  - A cell-based screen for drugs to treat Huntington's disease.
AB  - We have developed a medium-throughput cell-based assay to screen drugs for
      Huntington's disease (HD). The assay measures the ability of drugs to protect
      cultured neuronal (PC12) cells from death caused by an expanded polyglutamine
      (poly Q) form of huntingtin exon 1. Using this assay, we have blindly screened a
      library of 1040 compounds compiled by the NINDS: the NIH Custom Collection (NCC).
      Each compound was tested at five concentrations for its ability to protect cells
      against huntingtin-induced cell death as well as for its toxicity. Of the
      compounds tested, 18 prevented cell death completely, and 51 partially. Some of
      these also exhibited toxicity at higher doses. The majority of drugs (81%) were
      ineffective. Caspase inhibitors and cannabinoids showed reproducible protection
      in our assay. We believe these compounds, and others in our hit list, are
      appealing candidates for further investigation. Additionally, this assay is
      amenable to scaling up to screen additional compounds for treating Huntington's
      disease.

PMID- 15262267
TI  - Seizure evolution and amino acid imbalances in murine succinate semialdehyde
      dehydrogenase (SSADH) deficiency.
AB  - Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde
      dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to
      pharmacologic rescue, at 3-4 weeks of life. In the current report, we
      characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and
      regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to
      develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we
      found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate,
      glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine,
      homocarnosine, and arginine) as compared to age-matched littermates both before,
      and following, the period of generalized convulsive seizures and status
      epilepticus. Our results reveal imbalanced amino acid levels potentially involved
      in the transition from absence seizures to generalized convulsive seizures
      resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a
      unique epileptic model with the potential to reveal novel aspects of
      excitatory/inhibitory interactions in the genesis of seizures.

PMID- 15262268
TI  - Alteration of NO-producing system in the basal forebrain and hypothalamus of
      Ts65Dn mice: an immunohistochemical and histochemical study of a murine model for
      Down syndrome.
AB  - Ts65Dn mice have been developed as a model for Down syndrome (DS). Because of its
      involvement in complex behaviors, including sexual and aggressive behaviors, we
      investigated the nitric oxide (NO) system in specific brain regions of these
      mutant mice (TS) after isolation-induced aggression. Male TS mice displayed
      significantly higher aggression than wild type (WT) mice and the comparison of
      the NO system, both with immunohistochemical and histochemical methods, resulted
      in robust differences between TS and WT mice in the hypothalamic paraventricular
      nucleus, in the nucleus of the diagonal band and in the medial septum, but not in
      the striatum of TS mice. In conclusion, we document alterations in the neuronal
      NO system of the TS mouse model of DS, suggesting a correlation of the behavioral
      aggressiveness with deficient NO production.

PMID- 15262270
TI  - 3-Hydroxyglutaric acid fails to affect the viability of primary neuronal rat
      cells.
AB  - Glutaric aciduria type I (GA I) is an autosomal recessive inherited metabolic
      disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCD) resulting in
      the accumulation of 3-hydroxyglutaric acid (3OHG), glutaric acid and glutaconic
      acid in body fluids. GA I is characterized by a specific age- and brain region
      dependent neuropathology. Previous studies using organotypic slice cultures of
      rats and primary chick embryo telencephalon cell cultures indicated that death of
      neurons is a consequence of an excitotoxic mechanism induced by 3OHG. We used
      primary neuronal cells of neonatal rats as a model system to test cell viability
      after treatment with 3OHG. Western blot analysis was used to prove the expression
      of functional N-methyl-D-aspartate (NMDA) receptors revealing no alteration in
      the expression of NMDA-2a and -2b receptor subtypes in response to 3OHG. When
      neuronal cells cultured for 10 or 20 days were treated with 1 mM glutamate, the
      viability of cells was reduced by 40%. This effect could be prevented by
      coincubation with the NMDA receptor antagonist MK801. In contrast, incubation of
      cells with 3OHG for up to 24 h in concentrations of 4-8 mM did not cause
      increased cell death as compared with untreated control cultures. These results
      indicate that 3OHG is not excitotoxic in this model of neuronal rat cell cultures
      despite the presence of functional NMDA receptors. Therefore, alternative or
      additional pathomechanisms than excitotoxicity may be relevant for
      neurodegeneration in GA I.

PMID- 15262269
TI  - Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF
      protein expression in mice co-expressing mutant APP and PS1.
AB  - Transgenic mice expressing both mutant amyloid precursor protein (APPswe) and
      presenilin-1 (PS1DeltaE9) develop amyloid deposits as early as 4 months of age
      and preliminary evidence suggests that this may be associated with degenerative
      changes in serotonin axons innervating the dentate gyrus of the hippocampus. In
      the present investigation, which focused on further delineating the effects of
      amyloid deposition on hippocampal neurochemistry, decreases in serotonin
      neurotransmitter levels (-25%) were discovered to be present at 18 months in
      APP+/PS1+ mice, while norepinephrine was reduced in the hippocampus of 12- (-30%)
      and 18-month-old (-45%) APP+/PS1+ double mutants. In addition, brain-derived
      neurotrophic factor (BDNF) protein levels were investigated since changes in BDNF
      are reported to occur in AD, and BDNF has been shown to have trophic effects on
      serotonin and norepinephrine neurons. In doubly, but not singly mutant mice,
      hippocampal BDNF levels were increased at 12 (+70%) and 18 months (+170%).
      Furthermore, in a different model of serotonergic and noradrenergic degeneration,
      BDNF protein levels were similarly increased in response to depletions in
      hippocampal serotonin and norepinephrine caused by the chemical neurotoxin 1
      methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP). These
      findings show that early amyloid deposition in mice expressing mutant human APP
      and PS-1 is associated with a progressive loss of serotonin and norepinephrine
      neurotransmitter levels in the hippocampus later in life. Furthermore, BDNF
      protein levels are increased in APP+/PS1+ and 2'-NH2-MPTP-treated mice, possibly
      as a compensatory response to serotonergic and noradrenergic neurodegeneration in
      a brain region important for learning and memory.

PMID- 15262271
TI  - Neonatal hypoxic-ischemic injury increases forebrain subventricular zone
      neurogenesis in the mouse.
AB  - Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)
      olfactory bulb pathway and increases in the adult after brain insults. The
      influence of neonatal injury on SVZ neural precursors is unknown. We examined the
      effects of hypoxia-ischemia (HI) on neonatal mouse SVZ cell proliferation and
      neurogenesis. Postnatal day 10 (P10) mice underwent right carotid artery ligation
      followed by 10% O2 exposure for 45 min. The SVZ area and hemispheric injury were
      quantified morphometrically 1-3 weeks later. Bromodeoxyuridine (BrdU) was used to
      label proliferating cells, and cell phenotypes of the progeny were identified by
      immunohistochemistry. HI significantly enlarged the ipsilateral SVZ at P18, P24,
      and P31, and increases in the SVZ area correlated directly with the degree of
      hemispheric damage. HI also stimulated cell proliferation and neurogenesis in the
      SVZ and peri-infarct striatum. Some newborn cells expressed a neuronal phenotype
      at P24, but not at P31, indicating that neurogenesis was short-lived. These
      results suggest that augmenting SVZ neuroblast recruitment and survival may
      improve neural repair after neonatal brain injury.

PMID- 15262272
TI  - A preproenkephalin-neurofilament chimeric promoter in a helper virus-free herpes
      simplex virus vector enhances long-term expression in the rat striatum.
AB  - Helper virus-free herpes simplex virus (HSV-1) plasmid vectors are an attractive
      system for gene transfer into neurons in the brain, but promoters that support
      long-term, neuronal-specific expression are required. Elucidation of general
      principles that govern long-term expression would likely assist efforts to
      develop improved promoters. Although expression from many promoters in HSV-1
      vectors is unstable, two neuronal subtype-specific promoters, the
      preproenkephalin (ENK) promoter and the tyrosine hydroxylase (TH) promoter,
      support long-term expression. We have previously shown that 5' upstream sequences
      in the TH promoter are required for long-term expression, and addition of these
      upstream sequences to a neurofilament heavy gene (NF-H) promoter enhances long
      term, neuronal-specific expression. The goal of this study was to determine if
      the upstream sequences from the TH promoter contain a unique element that
      enhances expression, or if other neuronal promoters also contain sequences that
      can enhance expression. To this end, we tested 5' upstream sequences in the ENK
      promoter. We isolated a vector that fuses upstream sequences from the ENK
      promoter to the NF-H promoter. This vector supported expression in the striatum
      for 2 months after gene transfer, the longest time point evaluated. Expression
      was neuronal specific. As ENK and TH are a peptide neurotransmitter and a
      classical neurotransmitter biosynthetic enzyme, respectively, these results
      suggest that a significant number of promoters for neurotransmitter biosynthetic
      genes may contain elements that can enhance expression from HSV-1 vectors. The
      strategy of using upstream sequences from neuronal subtype-specific promoters to
      enhance expression from heterologous promoters is discussed.

PMID- 15262273
TI  - Destruction of extracellular matrix proteoglycans is pervasive in simian
      retroviral neuroinfection.
AB  - Disruption of the perineuronal matrix has been reported in human immunodeficiency
      virus (HIV) encephalitis. To better understand the extent of matrix disruption
      during lentiviral encephalitis, we characterized the extracellular matrix (ECM)
      damage in brains of 12 macaques infected with simian immunodeficiency virus
      (SIV). Matrix integrity was assessed by Wisteria floribunda lectin
      histochemistry. Confocal microscopy was used to quantify matrix loss, macrophage
      infiltration, and synaptic damage. Disruption of brain ECM was present shortly
      after retroviral infection, preceding parenchymal macrophage infiltration. In
      agreement with previous observations, reduced staining of presynaptic and
      postsynaptic proteins in SIV encephalitis occurred concurrently with matrix
      abnormalities. Lentiviral infection induced microglial and macrophage expression
      of two disintegrins and metalloproteinases with thrombospondin motifs (ADAMTS-1
      and ADAMTS-4), with high substrate specificity for matrix proteoglycans. Matrix
      damage is pervasive during SIV neuroinfection, which suggests interventions to
      conserve brain matrix proteoglycans might avert or delay retroviral-induced
      neurodegeneration.

PMID- 15262274
TI  - Deposition of amyloid fibrils promotes cell-surface accumulation of amyloid beta
      precursor protein.
AB  - Amyloid beta protein (Abeta) deposition and neuronal degeneration are
      characteristic pathological features of Alzheimer's disease (AD). In vitro, Abeta
      fibrils (fAbeta) induce neuronal degeneration reminiscent to AD, but the
      mechanism of neurotoxicity is unknown. Here we show that amyloid fibrils increase
      the level of cell-surface full-length amyloid beta precursor protein (h-AbetaPP)
      and secreted AbetaPP (s-AbetaPP). Pulse-chase analysis indicated that fAbeta
      selectively inhibited the turnover of cell-surface AbetaPP, without altering its
      intracellular levels. FAbeta-induced AbetaPP accumulation was not abrogated by
      cycloheximide, suggesting that increased protein synthesis is not critically
      required. Abeta fibrils sequester s-AbetaPP from the culture medium and promote
      its accumulation at the cell surface, indicating that binding of Abeta fibrils
      mediates AbetaPP accumulation. A time course analysis of Abeta treatment showed
      that AbetaPP level is elevated before significant cell death can be detected,
      while other toxic insults do not augment AbetaPP level, suggesting that AbetaPP
      may be specifically involved in early stages of Abeta-induced neurodegeneration.
      Finally, Abeta fibrils promote clustering of h-AbetaPP in abnormal focal adhesion
      like (FA-like) structures that mediate neuronal dystrophy, increasing its
      association with the cytoskeleton. These results indicate that the interaction of
      Abeta fibrils with AbetaPP is an early event in the mechanism of Abeta-induced
      neurodegeneration that may play a significant role in AD pathogenesis.

PMID- 15262275
TI  - CCR5 deficiency does not prevent P0 peptide 180-199 immunized mice from
      experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN) is an inflammatory autoimmune
      demyelinating disease of peripheral nervous system (PNS) and represents an animal
      model of Guillain-Barre syndrome (GBS) in man. The inflammatory cell infiltrating
      into the PNS is a prerequisite for developing EAN. To explore the role of CC
      chemokine receptor 5 (CCR5) in the inflammatory process of EAN, we induced EAN in
      CCR5-deficient (CCR5(-/-)) mice with P0 protein peptide 180-199. We found that
      CCR5(-/-) mice showed a similar EAN clinical course and severity as well as
      profile of infiltrating macrophages and T cells in cauda equina (CE) of EAN and
      the same levels of spleen mononuclear cell (MNC) response to antigen and mitogen
      when compared with CCR5(+/+) control mice. However, increased IP-10 and MIP-1beta
      production in sciatic nerves were seen in CCR5(-/-) mice. These results suggest
      that CCR5 deficiency does not prevent P0 peptide 180-199-immunized mice from EAN.
      Increased MIP-1beta and IP-10 in sciatic nerves may compensate the CCR5
      deficiency and contribute to inflammatory cells infiltrating to the PNS.

PMID- 15262276
TI  - Phrenic rehabilitation and diaphragm recovery after cervical injury and
      transplantation of olfactory ensheathing cells.
AB  - Functional respiratory recovery was evaluated by recording diaphragm and phrenic
      nerve activity several months after cervical cord hemisection followed by
      olfactory ensheathing cell (OEC) transplantation. The intact side was taken as a
      control in each rat. Sham-transplanted rats did not recover respiratory activity
      from the ipsilateral lesioned side. By contrast, ipsilateral phrenic and
      diaphragmatic activities recovered in transplanted rats amounted to 80.7% and 73%
      of their controls, respectively. After contralateral acute C1 section eliminating
      any contralateral influence from crossed compensatory pathways, the ipsilateral
      phrenic activity remained at 57.5% of the control, indicating that the phrenic
      recovery originated from the ipsilateral side. Supralesional stimulation in these
      rats elicited sublesional ipsilateral postsynaptic phrenic responses showing that
      transplantation helped ipsilateral fibers to again transmit nervous messages to
      the phrenic target, leading to substantial functional recovery. The origin of
      mechanisms involved in respiratory recovery (regeneration, resurrection,
      sprouting, sparing, demasking of latent pathways) is discussed.

PMID- 15262277
TI  - Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick
      disease type C.
AB  - Niemann-Pick disease type C (NP-C) is a hereditary neurovisceral lipid storage
      disorder. Although traditionally considered a primary cholesterol storage
      disorder, a variety of glycolipids accumulate in NP-C cells, which resemble those
      from glycosphingolipidosis patients. Substrate reduction therapy (SRT) with
      miglustat, an inhibitor of glycosphingolipid biosynthesis, is a novel therapy for
      the glycosphingolipidoses. We report the use of SRT in a patient with NP-C. We
      show that depletion of glycosphingolipids by miglustat treatment reduces
      pathological lipid storage, improves endosomal uptake and normalises lipid
      trafficking in peripheral blood B lymphocytes. The demonstration that treatment
      with miglustat, which has no direct effect on cholesterol metabolism, corrects
      the abnormal lipid trafficking seen in B lymphocytes in NP-C indicates that
      glycosphingolipid accumulation is the primary pathogenetic event in NP-C. These
      observations support the use of SRT in patients with this devastating
      neurodegenerative disease.

PMID- 15262278
TI  - Prophenoloxidase (proPO) activation in Manduca sexta: an analysis of molecular
      interactions among proPO, proPO-activating proteinase-3, and a cofactor.
AB  - Proteolytic activation of prophenoloxidase (proPO) is an integral part of the
      insect immune system against pathogen and parasite infection. This reaction is
      mediated by a proPO-activating proteinase (PAP) and its cofactor in the tobacco
      hornworm, Manduca sexta (Proc. Natl. Acad. Sci. USA 95 (1998) 12220; J. Biol.
      Chem. 278 (2003) 3552; Insect Biochem. Mol. Biol. 33 (2003) 1049). The cofactor
      consists of two serine proteinase homologs (SPHs), which associate with
      immulectin-2, a calcium-dependent lectin that binds to lipopolysaccharide (Insect
      Biochem. Mol. Biol. 33 (2003) 197). In order to understand the auxiliary effect
      of SPH-1 and SPH-2 in proPO activation, we started to investigate the molecular
      interactions among proPO, PAP-3, and the proteinase-like proteins. M. sexta SPH-1
      and SPH-2 were purified from hemolymph of prepupae by hydroxylapatite, gel
      filtration, lectin-affinity, and ion exchange chromatography. They existed as non
      covalent oligomers with an average molecular mass of about 790 kDa. MALDI-TOF
      mass fingerprint analysis revealed a new cleavage site in SPH-1 before Asp85. The
      PAP cofactor did not significantly alter Michaelis constant (KM) or kcat of PAP-3
      towards a synthetic substrate, acetyl-Ile-Glu-Ala-Arg-p-nitroanilide, but greatly
      enhanced proPO activation by PAP-3. The apparent KM for proPO was determined to
      be about 9.4 microg/ml, close to its estimated concentration in larval hemolymph.
      In the presence of excess proPO and a set amount of PAP-3, increasing levels of
      phenoloxidase (PO) activity were detected as more SPHs were added. Half of the
      maximum proPO activation occurred when the molar ratio of PAP-3 to SPH was 1:1.4.
      Gel filtration experiments suggested that proPO, PAP-3, and the cofactor formed a
      ternary complex.

PMID- 15262279
TI  - Significance of the sulfonylurea receptor (SUR) as the target of diflubenzuron in
      chitin synthesis inhibition in Drosophila melanogaster and Blattella germanica.
AB  - Diflubenzuron (DIMILIN) is a powerful insecticidal chemical which has been known
      for many years to inhibit chitin synthesis in vivo in insects and related
      arthropod species. However, its action mechanism has remained unresolved partly
      because of its inaction on any of the enzymes involved in chitin synthesis in
      vitro. Based on our previous work (Diflubenzuron affects gamma-thioGTP stimulated
      Ca2+ transport in vitro in intracellular vesicles from the integument of the
      newly molted American cockroach, Periplaneta americana L. Insect Biochem. Mol.
      Biol. 24 (1994) 1009) showing that diflubenzuron inhibits Ca2+ uptake by vesicles
      obtained from the integument of American cockroach, Periplaneta americana (L.),
      in vitro, we tested the hypothesis that the action site of diflubenzuron is an
      ABC (ATP binding cassette) transporter, probably a sulfonylurea-sensitive
      transporter. Glibenclamide, one of the most commonly used sulfonylureas for type
      II diabetes treatment, was the positive control. When given to immature insects,
      glibenclamide clearly caused toxicity, with symptoms indicating molting
      abnormality comparable to diflubenzuron. Its LD50 (0.472 microg/nymph) was
      approximately 2.8 times the value obtained for diflubenzuron (0.17 microg/nymph,
      topical) in German cockroach, Blattella germanica (L.). However, in terms of the
      inhibitory activities on chitin synthesis, in isolated integuments glibenclamide
      showed an identical potency to diflubenzuron in B. germanica nymphs. A
      competitive binding assay with [3H]-glibenclamide and unlabeled diflubenzuron
      clearly established that the latter is capable of competitively displacing the
      former radioligand. The KD values observed for vesicles prepared from fruit fly
      larvae, Drosophila melanogaster M., were 44.9 nM for glibenclamide and 65.0 nM
      for diflubenzuron, respectively. Furthermore, glibenclamide was found to affect
      Ca2+ uptake by isolated cuticular vesicles from B. germanica in a manner very
      similar to diflubenzuron. These results support our conclusion that the
      sulfonylurea receptor (SUR) is the target of diflubenzuron in inhibition of
      chitin synthesis in these two insect species.

PMID- 15262280
TI  - Comparative analysis of proteinase activities of Bacillus thuringiensis-resistant
      and -susceptible Ostrinia nubilalis (Lepidoptera: Crambidae).
AB  - Proteinase activities were compared in soluble and membrane fractions of guts
      obtained from larvae of Bacillus thuringiensis-resistant and -susceptible
      Ostrinia nubilalis. Overall, serine proteinases from soluble fractions of the
      susceptible strain were more active than those of the resistant strain. The
      soluble trypsin-like proteinase activity of the resistant strain was
      approximately half that of the susceptible strain. The number and relative
      molecular masses of soluble and membrane serine proteinases were different.
      However, there were no significant differences in the activities of serine
      proteinases and aminopeptidases extracted from midgut membranes of the two
      strains. Cry1Ab protoxin hydrolysis by soluble proteinase extracts of the
      resistant strain was reduced approximately 20-30% relative to that of the
      susceptible strain. Reduced protoxin processing due to decreased activities of Bt
      protoxin activation proteinases may be associated with resistance to Bt toxin in
      this resistant strain of O. nubilalis.

PMID- 15262281
TI  - The involvement of microsomal oxidases in pyrethroid resistance in Helicoverpa
      armigera from Asia.
AB  - Five contemporary strains of the bollworm Helicoverpa armigera Hubner from China,
      Pakistan and India, all with high resistance to pyrethroids, were compared with a
      standard susceptible strain that originated from the Cote D'Ivoire in the 1970s
      ('SCD'). Two of the Chinese strains ('YGF' and 'YGFP') were derived by laboratory
      selection from a third, field collected strain ('YG'). The strain 'YG' exhibited
      7-, 14- and 21-fold resistance to fenvalerate, cypermethrin and deltamethrin,
      respectively. After selection with fenvalerate for 14 generations ('YGF'), this
      increased to 1690-, 540- and 73-fold. Selection with a mixture of fenvalerate and
      piperonyl butoxide (PBO) for 14 generations ('YGFP') resulted in resistance
      ratios of 2510, 2920 and 286. The synergistic ratios to fenvalerate that resulted
      from pre-treatment of PBO were 5-, 462- and 12-fold in YG, YGF and YGFP strains,
      respectively. Resistance ratios for a Pakistani strain (PAK) were 2320-, 4100-
      and 223-fold to fenvalerate, cypermethrin and deltamethrin, respectively. The
      synergistic ratio of PBO to these pyrethroids was 450-, 950- and 11-fold. The
      strong synergism of pyrethroids by PBO implied that an oxidative metabolism could
      be involved in pyrethroid resistance in these resistant strains. The activities
      of cytochrome P450 monooxygenases from midguts of final instar larvae to p
      nitroanisole (PNOD), ethoxycoumarin (ECOD), methoxyresorufin (MROD) significantly
      increased in all the resistant strains when compared with the susceptible strain.
      This further implies that cytochrome P450 monooxygenases are involved in
      pyrethroid resistance in Asian H. armigera. Comparative in vitro studies of the
      metabolism of 14C-deltamethrin by midgut microsomes of the resistant PAK and
      susceptible SCD strains showed that the resistant strain had a much greater
      capacity than the susceptible strain for the metabolic degradation of
      deltamethrin. This enhanced metabolic degradation occurred in the presence of
      NADPH which suggested an oxidative detoxification. In the resistant strains,
      minor increases in glutathione S-transferase activity (to the substrates CDNB and
      DCNB), and esterase activity (to the substrate alpha-naphthyl acetate) further
      suggested that, of the putative metabolic mechanisms, oxidases are the most
      important. This study provides the first evidence that cytochrome P450
      monooxygenases are a major metabolic mechanism responsible for pyrethroid
      resistance in H. armigera from Asia.

PMID- 15262282
TI  - Microarray analysis of gene expression profiles in wing discs of Bombyx mori
      during pupal ecdysis.
AB  - Wing discs of holometabolous insects undergo dramatic morphological changes
      during metamorphosis, a process that is controlled by the actions of hundreds of
      gene products. Using cDNA microarrays constructed from 5086 ESTs, we monitored
      the gene expression profiles in wing discs of Bombyx mori at 13 time points
      during pupal ecdysis (day-4 fifth instar larvae to day-0 pupae). Of the 5086 ESTs
      on the microarrays, 2998 ESTs had significant signals in more than half of the
      experiments. Of the 2998 ESTs, genes represented by 683 ESTs showed significant
      perturbations during pupal ecdysis. Genes previously known to be induced during
      metamorphosis were identified, including E75, Urbain, Chitinases, and cuticle
      proteins. The expressions of genes represented by 59 ESTs induced at the
      beginning of wandering contained genes predicted to be involved in protein
      degradation, amino acid metabolism, and amino acid transport. The expressions of
      genes represented by 147 ESTs induced after the ecdysteroid peak had a role in
      cuticle synthesis, pigmentation, ion transport, protein transport, and
      transcription regulation. The expressions of genes represented by 85 ESTs
      repressed after the ecdysteroid peak were predicted to be involved in nucleotide
      and nucleic acid metabolism and cell cycle. This indicates the involvement of
      several biological processes in wing disc development during metamorphosis.

PMID- 15262284
TI  - Cloning and molecular characterization of a cubilin-related serine proteinase
      from the hard tick Haemaphysalis longicornis.
AB  - Serine proteinases are one of the largest proteolytic families of enzymes, and
      have diverse cellular activities in mammalian tissues. We report here the cloning
      and molecular characterization of a cDNA encoding the serine proteinase of the
      hard tick Haemaphysalis longicornis (HlSP). The HlSP cDNA is 1570 bp long and the
      deduced precursor protein consists of 464 amino acids with a predicted molecular
      mass of 50.4 kDa and a pI of 8.2. The preprotein, consisting of 443 amino acids,
      was predicted to include a complement C1r/C1s, Uegf, and bone morphogenic protein
      1 domain, a low-density lipoprotein receptor class A domain, and a catalytic
      domain. HlSP sequence analysis showed high similarity to serine proteinases
      reported from arthropods and vertebrate animal species. Two-dimensional
      immunoblot analysis revealed endogenous HlSP in adult tick extracts at 50 kDa.
      Endogenous HlSP was also expressed in all lifecycle stages of H. longicornis.
      Immunohistochemical studies detected the endogenous enzyme in the midgut
      epithelial cells of an adult tick. The Escherichia coli-expressed recombinant
      HlSP was demonstrated to degrade bovine serum albumin and hydrolyze the substrate
      Bz-L-Arg-pNA at the rate of 30.2 micromol/min/mg protein. Further, HlSP
      expression was up-regulated during a blood-feeding process, indicating its
      involvement in the digestion of host blood components.

PMID- 15262283
TI  - Purification and characterization of a mandibular organ protein from the American
      lobster, Homarus americanus: a putative farnesoic acid O-methyltransferase.
AB  - Methyl farnesoate (MF) appears to have important roles in the development,
      morphogenesis, and reproduction of crustaceans. To better understand the
      regulation of MF synthesis, we studied farnesoic acid O-methyltransferase
      (FAOMeT, the final enzyme in the MF biosynthetic pathway) in the American lobster
      (Homarus americanus). FAOMeT purified from mandibular organ (MO) homogenates had
      a MW of approximately 38,000. The sequences of trypsin fragments of purified
      FAOMeT were used to design PCR primers to amplify a cDNA fragment, which was used
      to isolate a full-length cDNA containing a single open reading frame (ORF) of 828
      bp encoding a protein of 276 amino acids. The deduced amino acid sequence of this
      putative FAOMeT protein contained two copies of a conserved approximately 135
      amino acid domain we term the CF (CPAMD8/FAOMeT) domain; single copies of this
      domain also occur in the human CPAMD8 protein (a member of the alpha-2
      macroglobulin family) and an uncharacterized Drosophila protein. The recombinant
      protein had no FAOMeT activity. However, its addition to MO homogenates from
      eyestalk ablated (ESA) lobsters increased enzyme activity by up to 75%,
      suggesting that FAOMeT may require an additional factor or modification (e.g.,
      phosphorylation) for its activation. The mRNA for the putative FAOMeT was
      primarily found in the proximal region of the MO, the predominant site of MF
      synthesis. FAOMeT transcripts were found in muscle tissue from ESA animals, but
      not in green gland, hepatopancreas, or in muscle tissue from intact animals.
      FAOMeT mRNA was also detected in embryos and larval stages. This is the first
      comprehensive report of this protein in the lobster, and is an important step in
      elucidating the functions of MF in these animals.

PMID- 15262285
TI  - Annotated expressed sequence tags for studies of the regulation of reproductive
      modes in aphids.
AB  - The damaging effect of aphids to crops is largely determined by the spectacular
      rate of increase of populational expansion due to their parthenogenetic
      generations. Despite this, the molecular processes triggering the transition
      between the parthenogenetic and sexual phases between their annual life cycle
      have received little attention. Here, we describe a collection of genes from the
      cereal aphid Rhopalosiphum padi expressed during the switch from parthenogenetic
      to sexual reproduction. After cDNA cloning and sequencing, 726 expressed sequence
      tags (EST) were annotated. The R. padi EST collection contained a substantial
      number (139) of bacterial endosymbiont sequences. The majority of R. padi cDNAs
      encoded either unknown proteins (56%) or housekeeping polypeptides (38%). The
      large proportion of sequences without similarities in the databases is related to
      both their small size and their high GC content, corresponding probably to the
      presence of 5'-unstranslated regions. Fifteen genes involved in developmental and
      differentiation events were identified by similarity to known genes. Some of
      these may be useful candidates for markers of the early steps of sexual
      differentiation.

PMID- 15262286
TI  - Female-specific regulation of cuticular hydrocarbon biosynthesis by dopamine in
      Drosophila melanogaster.
AB  - The role of dopamine (DA) is investigated in cuticular hydrocarbon biosynthesis
      in Drosophila melanogaster with three different approaches: use of DA-deficient
      mutants (dopa decarboxylase temperature sensitive mutants reared at restrictive
      temperature, and rescued by dopamine ingestion or by pale mutants partially
      rescued by a tyrosine hydroxylase construction), pharmacological treatments
      (tyrosine hydroxylase inhibitors) and topical application on decapitated flies.
      We report that DA specifically regulates diene hydrocarbon biosynthesis, which is
      female specific. Our results suggest that DA acts in adult flies within the first
      hours of imaginal life and that DA production from the brain is crucial for this
      process. Thus, DA contributes to reproduction in D. melanogaster by acting during
      a critical period during development of young adults.

PMID- 15262287
TI  - Characterization and cDNA cloning of midgut carboxypeptidases from Trichoplusia
      ni.
AB  - Carboxypeptidase A and carboxypeptidase B activities from the midgut of
      Trichoplusia ni larvae were characterized. In the T. ni larval midgut, the
      primary digestive carboxypeptidase activity was attributed to carboxypeptidase A,
      which was eight times more active than carboxypeptidase B. Both the midgut
      carboxypeptidase A and carboxypeptidase B exhibited maximal activities at pH 8.0
      8.5 and were similarly susceptible to inhibition by potato carboxypeptidase
      inhibitor and phenanthroline. The midgut carboxypeptidase activities were
      analyzed in T. ni larvae fed on various diet sources and the results indicated
      that midgut carboxypeptidase activities per milligram of gut were similar
      regardless of the amount of dietary proteins or amino acids. However, midgut
      carboxypeptidase A activity was significantly higher in larvae exposed to soybean
      trypsin inhibitor and was significantly lower in larvae fed on broccoli foliage.
      From the T. ni larval midgut, five putative carboxypeptidase cDNAs were cloned,
      demonstrating that midgut carboxypeptidase activities are composed of multiple
      carboxypeptidase types. Sequence analysis indicated that the midgut
      carboxypeptidases were produced as secreted proenzymes which could be activated
      after removal of an N-terminal activation fragment by a trypsin. Two cloned cDNAs
      are predicted to code for carboxypeptidase A and one cDNA is predicted to code
      for a putative carboxypeptidase B. The other two cDNAs are highly similar to
      carboxypeptidase A and carboxypeptidase B in sequences, but their activity was
      not predictable.

PMID- 15262288
TI  - Metabolic pathways for dietary lipids in the midgut of hematophagous
      Panstrongylus megistus (Hemiptera: Reduviidae).
AB  - The metabolism of dietary lipids in the anterior midgut of Panstrongylus megistus
      during blood digestion was studied. Fifth instar nymphs were fed a blood meal
      containing 7.1 +/- 0.4 mg of lipids, consisting mainly of triacylglycerol (TAG),
      and completed the overall process of digestion in about 20 days. Lipolysis of TAG
      and pathways for diacylglycerol (DAG) biosynthesis in the midgut were
      investigated by feeding the insects with [9,10-3H]-oleic acid-labeled triolein.
      Lumenal [3H]-triacylglycerol was hydrolyzed, generating mainly fatty acids (FA)
      and glycerol and to lesser extent, DAG. Almost no radioactivity associated with
      monoacylglycerol was found at any time. In midgut tissue, labeled fatty acids
      were incorporated into phosphatidic acid, DAG and TAG, whereas no significantly
      labeled monoacylglycerol was observed. In addition, the activities of enzymes
      related to DAG metabolism were assayed in non-blood fed midgut homogenates and at
      different times after feeding on a blood meal. Significant changes in the
      activities of phosphatidate phosphohydrolase (EC 3.1.3.4) and triacylglycerol
      lipase (EC 3.1.1.3) were observed during blood digestion, suggesting that these
      enzymes are important in regulating intracellular DAG synthesis and mobilization
      in midgut cells. Finally, the histological changes of lipid stores observed in
      anterior midgut confirmed the active process of uptake and trafficking of lipids
      performed by the enterocytes during blood digestion.

PMID- 15262289
TI  - A Kunitz type protease inhibitor related protein is synthesized in Drosophila
      prepupal salivary glands and released into the moulting fluid during pupation.
AB  - From the Drosophila virilis late puff region 31C, we microcloned two neighbouring
      genes, Kil-1 and Kil-2, that encode putative Kunitz serine protease inhibitor
      like proteins. The Kil-1 gene is expressed exclusively in prepupal salivary
      glands. Using a size mutant of the KIL-1 protein and MALDI-TOF analysis, we
      demonstrate that during pupation this protein is released from the prepupal
      salivary glands into the pupation fluid covering the surface of the pupa. 3-D
      structure predictions are consistent with the known crystal structure of the
      human Kunitz type protease inhibitor 2KNT. This is the first experimental proof
      for the extracorporal presence of a distinct Drosophila prepupal salivary gland
      protein. Possible functions of KIL-1 in the context of the control of proteolytic
      activities in the pupation fluid are discussed.

PMID- 15262290
TI  - High-throughput detection of knockdown resistance in Myzus persicae using allelic
      discriminating quantitative PCR.
AB  - The peach-potato aphid Myzus persicae (Sulzer) has developed resistance to
      pyrethroid insecticides as a result of a mechanism conferring reduced nervous
      system sensitivity, termed knockdown resistance (kdr). This reduced sensitivity
      is caused by two mutations, L1014F (kdr) and M918T (super-kdr), in the para-type
      voltage-gated sodium channel. We have developed a diagnostic dose bioassay to
      detect kdr and provide preliminary information on the genotype present. We also
      developed two allelic discrimination PCR assays to determine precisely the
      genotypes of the two mutations (L1014F and M918T) in individual M. persicae using
      fluorescent Taqman MGB probes. In combination with assays for elevated
      carboxylesterase levels and modified acetylcholinesterase (MACE), this suite of
      assays allows for rapid high-throughput diagnosis, in individual aphids, of the
      three main resistance mechanisms of practical importance in the UK.

PMID- 15262291
TI  - Estimating cardiovascular disease risk and the metabolic syndrome: a Framingham
      view.
AB  - The metabolic syndrome as currently defined by the Adult Treatment Panel III
      includes multiple components. This article describes the background for these
      components' inclusion in the syndrome,measurement of these factors, and the
      appropriate interventions. The factors are highly interrelated and the true
      utility of this diagnostic entity is under critical evaluation as new and
      existing data are evaluated concerning the role of the syndrome in the
      development of vascular disease and other clinical outcomes.

PMID- 15262292
TI  - Nutritional aspects in the causation and management of the metabolic syndrome.
AB  - This article emphasizes the importance of weight reduction in obese individuals
      as the main nutritional focus relevant to the metabolic syndrome. Although other
      nutrients influence insulin sensitivity, these effects are modest in comparison
      with the benefit achievable with weight reduction. This article therefore
      initially discusses the dramatic rise in the prevalence of the metabolic
      syndrome,especially in the Asian-Pacific region where insulin resistance and the
      high conversion rate to type 2 diabetes are almost certainly related to weight
      gain.

PMID- 15262293
TI  - Focus on lifestyle change and the metabolic syndrome.
AB  - The National Cholesterol Education Program's Adult Treatment Panel III identifies
      persons with multiple metabolic risk factors or "metabolic syndrome" as
      candidates for intensified therapeutic lifestyle changes. This article reviews
      the important role of weight reduction,diet, and exercise in improving the
      metabolic syndrome and its risk factors of abdominal obesity, impaired fasting
      glucose,dyslipidemia, and coagulation/inflammatory factors. The article also
      provides practical strategies.

PMID- 15262294
TI  - Management of metabolic syndrome: statins.
AB  - Individuals who have the metabolic syndrome are at increased risk for
      cardiovascular disease. Combined dyslipidemia is an important component of
      metabolic syndrome, contributing to excess cardiovascular risk. Lifestyle and
      pharmacologic interventions are warranted for effective management of this
      syndrome. This article discusses the current evidence supporting the use of
      statins and their beneficial impact on lipid and nonlipid aspects of metabolic
      syndrome-related pathology.

PMID- 15262295
TI  - Management of atherogenic dyslipidemia of the metabolic syndrome: evolving
      rationale for combined drug therapy.
AB  - Atherogenic dyslipidemia is prevalent in various conditions associated with
      central obesity, hypertension, hyperurecemia, and impaired beta-cell function
      (ie, the metabolic syndrome). Because of clinical trial evidence, most high-risk
      patients with atherogenic dyslipidemia require statin therapy. Coadministration
      of drugs targeted to reduction of low-density lipoprotein precursors, however,is
      likely to improve the metabolic profile of all non-high-density lipoproteins and
      produce a significant rise in high-density lipoprotein cholesterol. Large-scale
      clinical trials with combined drug therapy that show coronary heart disease (CHD)
      risk reduction or improvement in CHD are needed. It is also possible that new
      drugs are needed to target fatty acid metabolism and inflammation. As
      understanding of the metabolic origins of atherogenic dyslipidemia increases, it
      is possible that new targets of therapy will be identified and that new drug
      combinations will prove to be even more efficacious than those currently
      available for treatment of this condition.

PMID- 15262296
TI  - Fibrates in the metabolic syndrome and in diabetes.
AB  - There is increasing evidence that fibrates can reduce coronary artery disease.
      This finding seems to be particularly the case inpatients with the metabolic
      syndrome or with diabetes. Their beneficial effects can be explained partly by
      their effects on lipoproteins,but these effects may also result from some of
      their nonlipid pleotropic effects. Clinical trials are still needed to determine
      the potential role played by such pleotropic actions.

PMID- 15262297
TI  - Management of the metabolic syndrome-nicotinic acid.
AB  - Nicotinic acid effectively treats each of the common lipid abnormalities found in
      the metabolic syndrome, and much progress has recently been made in understanding
      its mechanisms of action. Early concern that nicotinic acid can precipitate or
      worsen diabetes has been eased with recent trials, which demonstrated its safety
      and effectiveness in insulin-resistant states. Furthermore, nicotinic acid
      prevents cardiovascular disease and death in persons with a high prevalence of
      risk factors for the metabolic syndrome. When used by an experienced physician
      and taken by a motivated patient, nicotinic acid can be safe and effective in
      treating the dyslipidemia of the metabolic syndrome.

PMID- 15262298
TI  - Management of metabolic syndrome: aspirin.
AB  - Cardiovascular disease (CVD), which includes myocardial infarction(MI), stroke,
      and peripheral vascular disease, remains the leading cause of death in the United
      States and in most developed countries. In the United States today, 25% of
      patients have metabolic syndrome-including those who have had a prior occlusive
      vascular disease event, those who are having an acute MI or ischemic stroke, and
      finally, the largest segment of the population,namely those who have not yet
      experienced a clinical CVD, but whose risks are substantial (10-year risk 10%).
      This article reviews the totality of evidence for aspirin in the treatment and
      prevention of CVD and emphasizes its importance as adjunctive therapy for
      patients with metabolic syndrome.

PMID- 15262299
TI  - Glitazones and the management of insulin resistance: what they do and how might
      they be used.
AB  - Thiazolidinediones (glitazones) are the only compounds currently available that
      specifically target tissue insulin resistance. The two currently available drugs
      in this class, pioglitazone and rosiglitazone,are approved by the Food and Drug
      Administration for the treatment of type 2 diabetes mellitus only. The
      therapeutic potential of the glitazones for other consequences of insulin
      resistance has stirred considerable interest, especially with regard to their
      potential beneficial impact on atherosclerotic cardiovascular disease and
      diabetes prevention. They also have been considered in the management of
      polycystic ovarian syndrome, nonalcoholic fatty liver disease, and other
      consequences of insulin resistance. The nonglycemic potential of glitazones is a
      clinical area in rapid evolution, wherein most data are on the impact of the
      glitazones onsurrogate markers that are associated with diseases, not on disease
      outcomes. This article provides insight and guidance to clinicians on the diverse
      nonglycemic potential of glitazones until conclusive outcome data become
      available.

PMID- 15262300
TI  - Metabolic syndrome: part II.

PMID- 15262301
TI  - Commentary: new developments in cutaneous oncology.

PMID- 15262302
TI  - Chemoprevention of skin cancer and photoaging.
AB  - Skin cancer and photoaging are thought to be the result of ultraviolet radiation
      exposure. "Chemoprevention" refers to the prevention of photoaging and skin
      cancer through the use of pharmacologic agents that inhibit or reverse the
      process of photoaging or carcinogenesis. As both carcinogenesis and photoaging
      are multi-step processes, tumor development may be halted at several prospective
      points of intervention. A wealth of research aimed at chemoprevention is
      emerging. In this article, a variety of potential chemopreventive agents are
      discussed, including vitamins, diet, aspirin and non-steroidal anti-inflammatory
      drugs, and topical agents. Although further studies are warranted to identify and
      determine the safety and efficacy of new chemotherapeutic agents, it is expected
      that both systemic and topical agents may soon be available that effectively
      prevent photoaging and skin cancer development.

PMID- 15262303
TI  - Medical therapies for non-melanoma skin cancer.
AB  - The epidemic of nonmelanoma skin cancer (NMSC) continues, in part due to aging of
      the world's population, the frequency of early childhood sunburns, and episodic
      intense recreational sun exposure as opposed to sun exposure related to outdoor
      occupations. A nonsurgical approach to selected skin cancers could potentially
      decrease the expense and morbidity of surgical treatment for NMSC. The increase
      of comorbid medical conditions in the elderly makes alternatives to surgical
      management preferable under certain circumstances. This review will discuss
      medical alternatives ranging from biologic response modifiers to COX-2 inhibitors
      to lifestyle modifications, as well as their roles in the management of NMSC.
      This preliminary information will expand to include more therapeutic options for
      NMSC in the future. Further clinical trials are needed to better elucidate
      possible alternative treatment strategies for NMSC.

PMID- 15262304
TI  - The development of actinic keratosis into invasive squamous cell carcinoma:
      evidence and evolving classification schemes.
AB  - Actinic keratosis is an incipient form of cutaneous squamous cell carcinoma.
      Consequently, actinic keratoses must be treated expeditiously to forestall their
      downward growth. Several classification schemes have been proposed to better
      categorize actinic keratoses, and to guide their diagnosis and treatment. Among
      these approaches is the "keratinocyte intraepithelial neoplasia" (KIN) system
      developed by Cockerell; Goldberg's concept of the "proliferative actinic
      keratosis" (PAK), and Berhane's emphasis on the "inflamed actinic keratosis"
      (IAK). In the future, disparate classification schemes may be unified into a
      single pragmatic approach which accurately reflects the biological process
      whereby actinic keratoses devolve into invasive squamous cell carcinoma.

PMID- 15262305
TI  - Current management strategies for cutaneous T-cell lymphoma.
AB  - Cutaneous T-Cell Lymphoma is a group of lymphomas characterized by a malignant
      proliferation of skin homing T cells. Prognosis is generally good and treatment
      is based on the stage of the disease with the goal of inducing remission.
      Patients with disease limited to the skin in the form of patches and plaques
      respond best to "skin directed therapy" with topical agents including
      corticosteroids, nitrogen mustard, carmustine, bexarotene gel, as well as
      phototherapy with ultraviolet B light, PUVA, or photodynamic therapy. Tazarotene
      and imiquimod show potential in the treatment of early CTCL. Patients with
      disease resistant to treatment or with advanced disease require more aggressive
      therapy in the form of total skin electron beam radiation, biologic response
      modifiers including interferon alpha, bexarotene, denileukin diftitox,
      extracorporeal photochemotherapy or combination therapy. The use of chemotherapy
      is used primarily for palliation. Allogeneic hematopoetic stem cell
      transplantation may represent a successful treatment for treatment resistant
      disease.

PMID- 15262306
TI  - Mechanisms of metastasis.
AB  - Metastasis is the process by which a primary malignancy establishes distant and
      discontiguous disease. It is a dreaded and ominous event that usually portends a
      worse prognosis, with greater tissue destruction, organ dysfunction, and
      potential mortality. Fortunately, metastasis is a rare event for nonmelanoma skin
      cancers (NMSC). Basal cell carcinomas (BCC) comprise the vast majority of NMSC
      (60-80%) and have a metastasis rate of only 0.0028%. For squamous cell carcinomas
      (SCC), the rate of metastasis is 2-6% and rises with certain high-risk features.
      Malignant melanoma (MM) is perhaps the most feared among common skin
      malignancies. It has a marked propensity for metastasis, and deaths from MM far
      outnumber the combined mortalities of both BCC and SCC. The 5-year survival of
      localized stage IA melanoma is 95%. This decreases to 67% for nodal disease and
      less than 20% for distant metastasis. Even more aggressive than MM are rare
      cutaneous tumors, such as Merkel cell carcinoma and malignant fibrous
      histiocytoma. This chapter will discuss the mechanisms of metastasis as they
      apply to cutaneous malignancies, particularly melanoma.

PMID- 15262307
TI  - Current technologies for the in vivo diagnosis of cutaneous melanomas.
AB  - The rising incidence of cutaneous malignant melanoma has been observed in the
      past decades. Currently, there is no cure for metastatic melanoma; only early
      diagnosis followed by prompt excision of cutaneous lesions ensures a good
      prognosis. The clinical ABCD rule is created as a framework for differentiating
      melanomas from benign pigmented skin lesions, and it serves as the basis for
      current clinical diagnosis. The ABCD rule relies on four simple clinical
      morphologies of melanoma: 1) Asymmetry, 2) Border irregularity, 3) Color
      variegation, and 4) Diameter greater than 6 mm. Although it is valuable, it has
      its limitations. Currently, the diagnostic accuracy for physicians is about 65%.
      This statistic implies that 1) melanomas with subtle signs are missed as benign
      lesions, and 2) benign lesions are over diagnosed as melanomas, which lead to
      unnecessary biopsies.

PMID- 15262308
TI  - Current melanoma staging.
AB  - American Joint Committee on Cancer (AJCC), TNM staging, represents the
      cornerstone of management for cutaneous melanoma. This staging system groups
      patients with similar prognoses and has important implications in optimizing
      management and treatment and conducting better clinical trials. T describes the
      extent of the primary tumor, N the extent of regional lymph node metastases, and
      M the extent of distant metastases. The AJCC staging system for cutaneous
      melanoma underwent significant revision in 2002. The revised, current AJCC
      staging system and the TNM classification are detailed in this review.

PMID- 15262309
TI  - Surgical margins for resection of primary cutaneous melanoma.
AB  - The increasing prevalence of melanoma in the United States is alarming. The
      limited efficacy of adjuvant therapies in successfully treating regional or
      distant disease underscores the importance of surgical treatment of primary
      cutaneous melanoma. The historic paradigm of wide margin excision (5 cm) with or
      with lymphadenectomy has been proven in multiple clinical trials to show no
      benefit of improved patient survival. Conservative margin resection of melanoma
      is a procedure of low morbidity that offers statistically identical outcomes and
      spares the patient excessive surgical efforts. Mohs micrographic surgery may have
      a role in the management of melanomas in anatomic sites where standard margins
      may prove difficult to achieve.

PMID- 15262310
TI  - Sentinel lymph node biopsy.
AB  - The introduction of sentinel lymph node biopsy (SLNB) has been an important
      development in the management of malignant melanoma. Lymph nodes have long been
      known to play a key role in melanoma metastasis. The importance of nodal staging
      accounted for the previous surgical practice of elective lymph node dissection
      (ELND) even with its controversial impact on final outcomes and associated
      morbidity. Although this morbidity has been reduced with the ability to identify
      the SLN, numerous questions have subsequently surfaced with respect to this
      procedure's utility and therapeutic efficacy. This chapter will focus on the
      indications for SLNB, as well as the current controversies surrounding this
      procedure.

PMID- 15262311
TI  - Surgical treatment of stage IV melanoma.
AB  - Surgical therapy plays an important role in the management of selected patients
      with metastatic melanoma. Patients are frequently symptomatic from metastatic
      lesions, have few effective therapeutic options, and are faced with dismal
      outcomes. Surgical resection may provide successful palliation of symptomatic
      lesions with low morbidity and operative mortality. In carefully selected
      patients, resections performed with curative intent may result in improved
      survival if a pattern of disease recurrence suggestive of favorable tumor biology
      is present, and if complete resection of tumor is achieved. Because the majority
      of post-surgical metastatic patients eventually relapse and succumb to distant
      disease, adjuvant immunotherapeutic strategies are currently being evaluated.

PMID- 15262312
TI  - Immunotherapy for melanoma.
AB  - The immunogenicity of melanoma and the identification of melanoma-associated
      antigens is the basis for immunotherapy. This review will discuss the current
      status of melanoma immunotherapy with a focus on non-specific cytokines and
      highly specific vaccines, including peptides, viruses, dendritic cells, and whole
      cell vaccines. The passive transfer of melanoma-specific monoclonal antibodies
      and T-cells will also be reviewed. The problem of tumor escape and the
      association of immunotherapy to autoimmunity will be discussed. The use of
      immunotherapy in combination with other therapeutic agents and genetic profiling
      to predict responses suggests that immunotherapy will continue to play a role in
      the treatment of melanoma.

PMID- 15262313
TI  - Treatment of toxic epidermal necrolysis syndrome with "disease-modifying" drugs:
      the controversy goes on.

PMID- 15262314
TI  - Nanotechnology and biosensors.
AB  - Nanotechnology is playing an increasingly important role in the development of
      biosensors. The sensitivity and performance of biosensors is being improved by
      using nanomaterials for their construction. The use of these nanomaterials has
      allowed the introduction of many new signal transduction technologies in
      biosensors. Because of their submicron dimensions, nanosensors, nanoprobes and
      other nanosystems have allowed simple and rapid analyses in vivo. Portable
      instruments capable of analyzing multiple components are becoming available. This
      work reviews the status of the various nanostructure-based biosensors. Use of the
      self-assembly techniques and nano-electromechanical systems (NEMS) in biosensors
      is discussed.

PMID- 15262315
TI  - Novel microbial nitrogen removal processes.
AB  - The present-day wastewater treatment practices can be significantly improved
      through the introduction of new microbial treatment technologies. Recently,
      several new processes for nitrogen removal have been developed. These new
      nitrogen removal technologies provide practicable options for treating nitrogen
      laden wastewaters. The new processes are based on partial nitrification of
      ammonium to nitrite combined with anaerobic ammonium oxidation. These processes
      include the single reactor system for high ammonia removal over nitrite (SHARON)
      process, which involves part conversion of ammonium to nitrite; the anaerobic
      ammonium oxidation (ANAMMOX) process, which involves anaerobic ammonium
      oxidation; and the completely autographic nitrogen removal over nitrite (CANON)
      process, which involves nitrogen removal within one reactor under oxygen-limited
      conditions. These new processes target the removal of nitrogen from wastewaters
      containing significant quantities of ammonium.

PMID- 15262316
TI  - State of the art of biogranulation technology for wastewater treatment.
AB  - Biogranulation technology developed for wastewater treatment includes anaerobic
      and aerobic granulation processes. Anaerobic granulation is relatively well
      known, but research on aerobic granulation commenced only recently. Many full
      scale anaerobic granular sludge units have been operated worldwide, but no report
      exists of similar units for aerobic granulation. This paper reviews the
      fundamentals and applications of biogranulation technology in wastewater
      treatment. Aspects discussed include the models of biogranulation, major factors
      influencing biogranulation, characteristics of biogranules, and their industrial
      applications. This review hopes to provide a platform for developing novel
      granules-based bioreactors and devising a unified interpretation of the formation
      of anaerobic and aerobic granules under various operation conditions.

PMID- 15262317
TI  - Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in
      the hypothalamic paraventricular nucleus: possible role in desensitization of 5
      hydroxytryptamine1A receptors.
AB  - Desensitization of post-synaptic serotonin1A (5-HT1A) receptors may underlie the
      clinical improvement of neuropsychiatric disorders. In the hypothalamic
      paraventricular nucleus, Galphaz proteins mediate the 5-HT1A receptor-stimulated
      increases in hormone release. Regulator of G protein signaling-Z1 (RGSZ1) is a
      GTPase-activating protein selective for Galphaz proteins. RGSZ1 regulates the
      duration of interaction between Galphaz proteins and effector systems. The
      present investigation determined the levels of RGSZ1 in the hypothalamic
      paraventricular nucleus of rats subjected to four different treatment protocols
      that produce desensitization of 5-HT1A receptors. These protocols include: daily
      administration of beta estradiol 3-benzoate (estradiol) for 2 days; daily
      administration of fluoxetine for 3 and 14 days; daily administration of cocaine
      for 7 or 14 days; and acute administration of (+/-)-1-(2,5 dimethoxy-4
      iodophenyl)-2-amino-propane HCl (DOI; a 5-HT2A/2C receptor agonist). Estradiol
      treatment was the only protocol that increased the levels of RGSZ1 protein in the
      hypothalamic paraventricular nucleus in a dose-dependent manner (46%-132% over
      control). Interestingly, previous experiments indicate that only estradiol
      produces a decreased Emax of 5-HT1A receptor-stimulation of hormone release,
      whereas fluoxetine, cocaine and DOI produce a shift to the right (increased
      ED50). Thus, the desensitization of 5-HT1A receptors by estradiol might be
      attributable to increased levels of RGSZ1 protein. These findings may provide
      insight into the adaptation of 5-HT1A receptor signaling during pharmacotherapies
      of mood disorders in women and the well-established gender differences in the
      vulnerability to depression.

PMID- 15262318
TI  - Extrapyramidal motor symptoms versus striatal infarction volume after focal
      ischemia in mongolian gerbils.
AB  - Few behavioral tests are available to evaluate extrapyramidal dysfunctions after
      focal cerebral ischemia in rodents, although extrapyramidal motor dysfunctions
      are often observed clinically in patients with cerebral infarction. We evaluated
      the methamphetamine (MP)-induced rotation test for the detection and
      quantification of extrapyramidal motor dysfunction induced by striatal infarction
      in gerbils after focal cerebral ischemia. Mongolian gerbils (n=79) underwent the
      left common carotid artery occlusion (CCAO) for 10, 15, or 20 min. Spontaneous
      and MP-induced rotation tests were repeated postischemia, and the results
      compared with the extent of ischemic tissue injury. The density of dopaminergic
      neurons immunostained with a tyrosine hydroxylase antibody in the substantia
      nigra pars compacta (SNpc) also was measured. Histological examination revealed
      selective neuronal death of the hippocampal cornu ammonis 1 (CA1) sector in 10
      min CCAO animals, infarction confined to the striatum and hippocampal neuronal
      death in 15-min CCAO animals, and widespread hemispheric infarction in 20-min
      CCAO animals. Dopaminergic neurons in the SNpc were preserved in 10- and 15-min
      CCAO animals but were significantly reduced in 20-min CCAO animals. In MP-induced
      rotation tests, 15-min CCAO animals showed biased rotation ipsilateral to the
      lesioned side. Biased rotation persisted 4 weeks postischemia, and the number of
      rotations significantly correlated with the regional infarction volume of the
      striatum. Twenty-minute CCAO animals showed biased rotation contralateral to the
      lesioned side; rotation number was not correlated with the infarction volume. Our
      results show that biased rotation behavior is a sensitive parameter of the extent
      of striatal injury after focal cerebral ischemia provided the lesion is not
      extended to the ipsilateral cortex. MP-induced rotation in rodents probably
      coordinates with the extrapyramidal motor dysfunction after striatal infarction
      in patients with vascular Parkinsonism.

PMID- 15262319
TI  - Extinction deficit and fear reinstatement after electrical stimulation of the
      amygdala: implications for kindling-associated fear and anxiety.
AB  - Generalized seizures produced by electrical kindling of the amygdala in
      laboratory rats are a widely used animal model of temporal lobe epilepsy. In
      addition to seizure evolution amygdala kindling enhances emotionality. The
      relative roles of electrical stimulation and seizure induction in fear responding
      are unclear. Here we investigate this issue using extinction and reinstatement of
      fear-potentiated startle. After classical conditioning (light+footshock pairings)
      laboratory rats were fear extinguished with each light presentation followed by
      nonepileptogenic amygdala stimulation. In contrast to the normal extinction
      learning of control subjects, amygdala stimulated animals exhibited conditioned
      fear after 120 presentations of the nonreinforced conditioned stimulus (CS). In a
      second experiment electrical stimulation of the amygdala restored extinguished
      fear responding and the fear reinstatement was specific to extinction context.
      The reinstatement effect did not involve sensitized fear to the CS produced by
      amygdala stimulation. The possibility that electrical activation of the amygdala
      produces unconditioned fear was considered. Animals uniformly failed to
      demonstrate fear-potentiated startle using electrical stimulation of the amygdala
      as the unconditioned stimulus. This was the case with a subthreshold
      afterdischarge stimulus and a stimulation schedule that produced kindled
      seizures. The extinction deficit and fear reinstatement results were interpreted
      to suggest that amygdala stimulation activates acquired excitatory stimulus
      affect neural connections formed during Pavlovian fear conditioning. Our data
      supports a model in which excitation of an amygdala-based memory-retrieval system
      reinforces the expression of learned fear behaviors.

PMID- 15262320
TI  - Dissociation of function within the hippocampus: effects of dorsal, ventral and
      complete excitotoxic hippocampal lesions on spatial navigation.
AB  - The present study was designed to assess the possibility that sub-total ventral
      hippocampal lesions might leave intact a mechanism for only highly accurate
      navigation, whereas sub-total dorsal hippocampal lesions might leave intact a
      mechanism only for less precise navigation. Animals with selective dorsal,
      ventral or complete hippocampal lesions were tested in a water maze, in which the
      target platform was moved from trial to trial, but always within a defined area,
      instead of being at a fixed location. Hence, an animal that searched at exactly
      the point where the platform had been found on a previous trial would be
      disadvantaged, in comparison with an animal that searched in the right general
      area. This might favor animals capable of less precise navigation over those with
      very precise navigational abilities. In subsequent phases of the experiment, we
      additionally assessed, for comparison, performance with a fixed platform
      location, reversal learning in the water-maze, and performance on an elevated T
      maze. Our results revealed no sign of any qualitative difference between the
      effects of the selective sub-total lesions when the water maze hidden platform
      location was varied within the defined area, and the effects in subsequent more
      conventionally used tests. Ventral hippocampal damage never led to a performance
      deficit. Dorsal hippocampal damage led to significantly poorer performance in
      only some test phases, and never led to any sign of improved performance.

PMID- 15262321
TI  - Regressive and reactive changes in the connectivity patterns of rod and cone
      pathways of P23H transgenic rat retina.
AB  - We have used the P23H line 1 homozygous albino rat to study how progressive
      photoreceptor degeneration affects rod and cone relay pathways. We examined P23H
      retinas at different stages of degeneration by confocal microscopy of
      immunostained sections and electroretinogram (ERG) recordings. By 21 days of age
      in the P23H rat retina, there is already substantial loss of rods and reduction
      in rod bipolar dendrites along with reduction of metabotropic glutamate receptor
      6 (mGluR6) and rod-associated bassoon staining. The cone pathway is relatively
      unaffected. By 150 days, when rods are absent from much of the retina, some rod
      bipolars remain and dendrites of rod and cone bipolar cells form synaptic
      complexes associated with cones and horizontal cell processes. These complexes
      include foci of mGluR6 and bassoon staining; they develop further by 270 days of
      age. Over the course of degeneration, beginning at 21 days, bipolar axon
      terminals atrophy and the inner retina undergoes further changes including a
      reduced and disorganized AII amacrine cell population and thinning of the inner
      plexiform layer. Electroretinogram (ERG) results at 23 days show reductions in a
      wave amplitude, in rod and cone-associated b-waves (using a double flash
      paradigm) and in the amplitude of oscillatory potentials (OPs). By 38 days, rod
      scotopic a-wave responses and OPs are lost. B-wave amplitudes decline until 150
      days, at which point they are purely cone-driven and remain stable up to 250
      days. The results show that during the course of photoreceptor loss in the P23H
      rat, there are progressive degenerative changes, particularly in the rod relay
      pathway, and these are reflected in the changing ERG response patterns. Later
      reactive changes involving condensation of cone terminals and neurotransmitter
      receptors associated with rod and cone bipolar dendrites and with horizontal cell
      processes suggest that at this stage, there are likely to be complex changes in
      the relay of sensory information through the retina.

PMID- 15262322
TI  - Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington's
      disease.
AB  - The presence of ongoing neurogenesis in the adult mammalian brain raises the
      exciting possibility that endogenous progenitor cells may be able to generate new
      neurons to replace cells lost through brain injury or neurodegenerative disease.
      We have recently demonstrated increased cell proliferation and the generation of
      new neurons in the Huntington's disease human brain. In order to better
      understand the potential role of endogenous neuronal replacement in
      neurodegenerative disorders and extend our initial observations in the human
      Huntington's disease brain, we examined the effect of striatal cell loss on
      neurogenesis in the subventricular zone (SVZ) of the adult rodent forebrain using
      the quinolinic acid (QA) lesion rat model of Huntington's disease. Cell
      proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU)
      labeling and immunocytochemistry for cell type-specific markers. BrdU labeling
      demonstrated increased cell proliferation in the SVZ ipsilateral to the QA
      lesioned striatum, resulting in expansion of the SVZ in the lesioned hemisphere.
      Quantification revealed that QA lesion-induced striatal cell loss produced a
      significant increase in the area of BrdU-immunoreactivity in the SVZ ipsilateral
      to the lesioned hemisphere between 1 and 14 days post-lesion compared with sham
      lesioned animals, with the greatest increase observed at 7 days post-lesion.
      These changes were associated with an increase in cells in the anterior SVZ
      ipsilateral to the lesioned striatum expressing the antigenic marker for SVZ
      neuroblasts, doublecortin (Dcx). Importantly, we observed Dcx-positive cells
      extending from the SVZ into the QA-lesioned striatum where a subpopulation of
      newly generated cells expressed markers for immature and mature neurons. This
      study demonstrates that loss of GABAergic medium spiny projection neurons
      following QA striatal lesioning of the adult rat brain increases SVZ
      neurogenesis, leading to the putative migration of neuroblasts to damaged areas
      of the striatum and the formation of new neurons.

PMID- 15262323
TI  - MR image-guided investigation of regional signal transducers and activators of
      transcription-1 activation in a rat model of focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: STAT-1 is a member of a family of proteins called signal
      transducers and activators of transcription (STATs), and recent studies have
      shown its involvement in the induction of apoptosis. There is limited information
      on the role of STAT-1 following stroke. In this study we use MRI measurements of
      cerebral perfusion and bioenergetic status to target measurements of regional
      STAT-1 activity. METHODS: Rats were subjected to 60 or 90 min of middle cerebral
      artery occlusion with and without reperfusion. MRI maps of the apparent diffusion
      coefficient of water and cerebral blood flow were acquired throughout the study.
      After the ischemia or reperfusion period, the brain was excised and samples were
      analyzed by Western blots using anti-phospho-STAT1 and anti-Fas antibodies.
      Regions were selected for analysis according to their MRI characteristics.
      RESULTS: Transcriptional factor STAT-1 was enhanced in the lesion core and, to a
      lesser extent, in the lesion periphery, following ischemia and reperfusion. This
      level of activity was greater than for ischemia alone. Western blots demonstrated
      STAT-1 phosphorylation on tyrosine 701 and not serine 727 after ischemia and 3 h
      of reperfusion. Enhanced expression of the apoptotic death receptor Fas was
      confirmed after ischemia followed by reperfusion. CONCLUSIONS: This study
      demonstrates that focal ischemia of the rat brain can induce STAT-1 activation,
      particularly following a period of reperfusion. The activation occurs not only in
      the lesion core, but also in the lesion periphery, as identified using MRI. STAT
      1 may play an important role in the induction of cell death following stroke.

PMID- 15262324
TI  - GABA neurons survive focal ischemic injury.
AB  - Focal cerebral lesions in rat brain induced by photothrombosis lead to an
      impaired inhibitory neurotransmission. A reduced gamma-aminobutyric acid (GABA)
      mediated inhibition has been revealed by electrophysiological recordings
      associated with a diminished immunostaining of GABA handling proteins. Changes
      were found in ipsi- as well as in contralateral brain areas. Inhibition is
      mediated by interneurons using GABA as neurotransmitter. These cells use GAD
      (glutamate decarboxylase) to synthesize GABA. To analyze the vulnerability of
      GABAergic neurons in rats with a lesioned hindlimb area, cells expressing
      GAD65/67 mRNA were labeled using in situ hybridization. Positive somata were
      counted 7 and 30 days after focal ischemia in different cortical (hindlimb
      cortex, frontal cortex, primary and secondary somatosensory cortex) and
      hippocampal subsectors (pyramidal cell layer, stratum oriens and stratum
      radiatum/lacunosum-moleculare). The lesioned hemispheres were compared with the
      intact brain sides and with control brains. GABAergic interneurons survived the
      injury for up to 30 days in all investigated brain regions. Therefore it is
      unlikely that a loss of GABAergic neurons contributes to the reduced inhibition.

PMID- 15262325
TI  - Functional magnetic resonance tomography correlates of taste perception in the
      human primary taste cortex.
AB  - The present study investigated the functional magnetic resonance tomography
      correlates of taste perception in the human primary taste cortex. There is
      conflicting evidence in the literature about chemotopical organization in this
      brain region. The topography of hemodynamic activity elicited by five taste
      stimuli (sweet, sour, salty, bitter and umami) was analyzed on the flattened
      cortical surfaces of six single subjects. A high inter-individual topographical
      variability had to be noted. The results showed different patterns of hemodynamic
      activity for the investigated tastes with some considerable overlap. However, the
      taste specific patterns were stable over time in each subject. Such an individual
      taste specific pattern was also found for the umami taste within the primary
      taste cortex of each subject. These results suggest that input from glutamate
      receptors on the tongue might be processed in an exclusive way in the primary
      taste cortex rather than as a combination of inputs from the classical taste
      receptors.

PMID- 15262326
TI  - Effect of hypoxia on protein phosphatase 2A activity, subcellular distribution
      and expression in cerebral cortex of newborn piglets.
AB  - Protein phosphatase (PP) 2A (PP2A), a major serine/threonine phosphatase highly
      active in the brain, is known to regulate programmed cell death by different
      mechanisms including downregulation of Ca++/calmodulin-dependent kinase IV (CaMK
      IV). Previous studies have shown that CaMK IV activity is increased following
      cerebral hypoxia. In the present study, we tested the hypothesis that PP2A
      activity and expression in neuronal nuclei are decreased following hypoxia in
      newborn piglets. PP and PP2A activities were determined in cerebral subcellular
      fractions spectrophotometrically using a serine phosphopeptide in the presence or
      absence of microcystine. The activity of CaMK IV in neuronal nuclei was
      determined by 33P-incorporation into syntide 2 in the presence or absence of
      either 1 mM EGTA or 0.8 mM CaCl2 and 1 mM calmodulin. The expressions of PP2A and
      CaMK IV were measured using Western blot. Following hypoxia, nuclear Ca++
      dependent kinase IV activity increased two-fold (P<0.001), whereas PP2A and PP
      activities significantly decreased (P<0.05) in the neuronal nuclei and membranes
      but not in the cytosol (P=NS). The distribution of the activity of PP2A was 60%
      in the cytosol, 35% in membranes and 5% in the neuronal nuclei. The expression of
      PP2A protein showed a 14% increase and for CaMK IV protein a 100% increase during
      hypoxia. We propose that due to the decreased activity of PP and PP2A following
      hypoxia in the neuronal nuclei there is a shift in the balance of the
      phosphorylation/dephosphorylation system toward increased phosphorylated state
      thereby increasing activity of the nuclear CaMK IV, modulator of programmed cell
      death. Since there is only slight increase in the PP2A protein expression, we
      conclude that the changes observed in the activity of PP2A are due to hypoxia
      induced modification of the enzyme itself. We also provide evidence that PP2A is
      a potential regulator of CaMK IV during hypoxia.

PMID- 15262327
TI  - Characterization of gabaergic neurons within the human medial mamillary nucleus.
AB  - The morphology, distribution and relative frequency of GABAergic neurons in the
      medial mamillary nucleus (MMN) of normal human individuals was studied using a
      glutamic acid decarboxylase (GAD) antiserum. GAD-immunoreactive (GAD-IR) neurons
      were found sparsely distributed throughout the MMN and most displayed a simple
      bipolar morphology. A small population of large diameter GAD-IR neurons was found
      in the white matter capsule adjacent to the ventral border of the MMN. Results of
      double-labeling experiments revealed no evidence of calretinin, parvalbumin or
      calbindin immunoreactivities co-localizing with GAD-IR neurons. GAD-IR neurons of
      the MMN had an average somal area of 138+/-41 microm2, compared with the average
      somal area of 384+/-137 microm2 for the population of MMN neurons as a whole. GAD
      IR neurons had a tendency to cluster in groups of two (and occasionally three)
      and showed a distribution gradient across the MMN with higher densities being
      found near the insertion of the fornix, the origin of the mamillo-thalamic tract
      and toward the medial MMN border. Quantitative estimates of GAD-IR neuron
      frequency revealed the GAD-IR phenotype to constitute an average of 1.7% percent
      of the total neuron population within the human MMN. These findings suggest that
      inhibitory activity within the human MMN is regulated in part by a small
      population of intrinsic GABAergic interneurons.

PMID- 15262328
TI  - Administration of a non-NMDA antagonist, GYKI 52466, increases excitotoxic
      Purkinje cell degeneration caused by ibogaine.
AB  - Ibogaine is a tremorigenic hallucinogen that has been proposed for clinical use
      in treating addiction. We previously reported that ibogaine, administered
      systemically, produces degeneration of a subset of Purkinje cells in the
      cerebellum, primarily within the vermis. Ablation of the inferior olive affords
      protection against ibogaine-induced neurotoxicity leading to the interpretation
      that ibogaine itself is not directly toxic to Purkinje cells. We postulated that
      ibogaine produces sustained excitation of inferior olivary neurons that leads to
      excessive glutamate release at climbing fiber terminals, causing subsequent
      excitotoxic injury to Purkinje cells. The neuronal degeneration induced by
      ibogaine provides an animal model for studying excitotoxic injury in order to
      analyze the contribution of glutamate receptors to this injury and to evaluate
      neuroprotective strategies. Since non-N-methyl-D-aspartate (NMDA) receptors
      mediate Purkinje cell excitation by climbing fibers, we hypothesized that 1-4
      aminophenyl-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI-52466), which
      antagonizes non-NMDA receptors, may have a neuroprotective effect by blocking
      glutamatergic excitation at climbing fiber synapses. To test this hypothesis,
      rats were administered systemic ibogaine plus GYKI-52466 and the degree of
      neuronal injury was analyzed in cerebellar sections. The results indicate that
      the AMPA antagonist GYKI-52466 (10 mg/kg i.p. x 3) does not protect against
      Purkinje cell injury at the doses used. Rather, co-administration of GYKI-52466
      with ibogaine produces increased toxicity evidenced by more extensive Purkinje
      cell degeneration. Several hypotheses that may underlie this result are
      discussed. Although the reason for the increased toxicity found in this study is
      not fully explained, the present results show that a non-NMDA antagonist can
      produce increased excitotoxic injury under some conditions. Therefore, caution
      should be exercised before employing glutamate antagonists to reduce the risk of
      neuronal damage in human clinical disorders. Moreover, the contribution of
      different glutamate receptors to excitotoxic injury is complex and merits further
      analysis.

PMID- 15262329
TI  - Activation of brain areas in rat following warm and cold ambient exposure.
AB  - Environmental thermal stimuli result in specific and coordinated thermoregulatory
      response in homeothermic animals. Warm exposure activates numerous brain areas
      within the cortex, hypothalamus, pons and medulla oblongata. We identified these
      thermosensitive cell groups in the medulla and pons that were suggested but not
      outlined by previous physiological studies. Using Fos immunohistochemistry, we
      localized all the nuclei and cell groups in the rat brain that were activated by
      warm and cold ambient exposure. These neurons located in the hypothalamus and the
      brainstem, are part of a network responsible for the thermospecific response
      elicited by thermal stress. Comparison of the distribution of Fos-immunoreactive
      cells throughout the rat brain revealed topographical differences between the
      patterns of activated cells following warm and cold environmental exposure. Among
      several brain regions, warm exposure elicited c-fos expression specifically in
      the ventrolateral part of the medial preoptic area, the central subdivision of
      the lateral parabrachial nucleus and the caudal part of the peritrigeminal
      nucleus, whereas cold stress resulted in c-fos expression in the ventromedial
      part of the medial preoptic area, the external subdivision of the lateral
      parabrachial nucleus and the rostral part of the peritrigeminal nucleus. These
      neurons are part of a network coordinating specific response to warm or cold
      exposure. The topographical differences suggest that well-defined cell groups and
      subdivisions of nuclei are responsible for the specific physiological (endocrine,
      autonomic and behavioral) changes observed in different thermal environment.

PMID- 15262330
TI  - Selective recovery of striatal 125I-alpha-conotoxinmii nicotinic receptors after
      nigrostriatal damage in monkeys.
AB  - Evidence suggests that nicotinic receptors play a role in nigrostriatal function,
      a finding that may be relevant to Parkinson's disease. Knowledge of the
      conditions that regulate nicotinic receptor expression is therefore important.
      Previous studies showed that several different nicotinic receptors, including
      alpha-conotoxinMII (alpha-CtxMII)-sensitive receptors, are decreased after
      nigrostriatal damage. Nigrostriatal dopaminergic terminals also demonstrate a
      capacity for recovery after lesioning. The present experiments were therefore
      done to determine whether there were changes in striatal nicotinic receptors with
      recovery. To address this, we used two well-characterized animal models of
      nigrostriatal damage produced using the selective dopaminergic neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Studies in mice showed that
      striatal 125I-alpha-CtxMII, as well as 125I-epibatidine and 125I-A85380 binding
      sites significantly recovered 1 month after lesioning, suggesting that alpha6*
      and most likely alpha4* receptors are increased. Experiments were next done in
      monkeys since striatal 125I-alpha-CtxMII receptors constitute a large percentage
      of nicotinic receptors and are more vulnerable to nigrostriatal damage in this
      model that closely mirrors Parkinson's disease. In monkeys allowed to recover
      from the toxic effects of MPTP for a 1-2 year period, there was a significant
      improvement in the Parkinson disability score. There was also a reversal in
      lesion-induced declines in striatal alpha-CtxMII-sensitive receptors, but no
      significant change in 125I-epibatidine and 125I-A85380 receptors. These findings
      suggest that alpha3*/alpha6* sites are selectively increased in monkey striatum
      with recovery. The present data show that recovery of 125I-alpha-CtxMII receptors
      occurs in parallel with the dopamine transporter, indicating that these nicotinic
      receptors sites are localized to presynaptic dopamine terminals in both species.

PMID- 15262331
TI  - GABA, in some cases together with glycine, is used as the inhibitory transmitter
      by pump cells in the Hering-Breuer reflex pathway of the rat.
AB  - The Hering-Breuer reflex is one of the fundamental respiratory reflexes and is
      mediated by second-order relay neurons of the slowly adapting lung stretch
      receptors. These neurons, which are called pump cells, are located in the nucleus
      tractus solitarii and include a population of inhibitory neurons. We aimed to
      determine which transmitter, GABA or glycine, the inhibitory pump cells use. In
      addition, we examined whether or not second-order relay neurons of the rapidly
      adapting lung stretch receptors (RAR-cells), whose excitatory or inhibitory
      nature is not known, use these inhibitory neurotransmitters. In Nembutal
      anesthetized, neuromuscularly blocked and artificially ventilated rats, we
      labeled pump cells (n=33) and RAR-cells (n=26) with Neurobiotin and processed the
      tissues for detection of mRNA encoding either glutamic acid decarboxylase isoform
      67 (GAD67) or glycine transporter 2 (GLYT2) using in situ hybridization. The pump
      cells were located in the interstitial nucleus and its vicinity and the RAR-cells
      in the commissural subnucleus. The majority (64%) of the pump cells examined for
      GAD67 mRNA and many (26%) of the pump cells examined for GLYT2 mRNA expressed
      respective mRNAs. Of the eight pump cells in which both mRNAs were double
      detected, three expressed both mRNAs and one expressed GAD67 mRNA but not GLYT2
      mRNA, the other four expressing neither mRNAs. On the other hand, RAR-cells
      expressed neither GAD67 mRNA nor GLYT2 mRNA. The results suggest that the
      inhibitory pump cells are basically GABAergic and some of them may corelease GABA
      and glycine, and that RAR-cells are neither GABAergic nor glycinergic. These
      findings expand our understanding of the networks of lung receptor-mediated
      reflexes including the Hering-Breuer reflex.

PMID- 15262332
TI  - Immunohistochemical study of the expression of exon11-containing mu opioid
      receptor variants in mouse brain.
AB  - The cloned mu opioid receptor MOR-1 undergoes alternative splicing. Extensive 3'
      splicing downstream from exon 3 leads to a number of C-terminal splice variants
      that are differentially expressed within the CNS. Recently, 5'-splicing has been
      observed with eight additional variants containing exon 11, a new exon located
      approximately 10 kb upstream from exon 1 that is under the control of a different
      promoter located even further upstream. Three of these variants generate the same
      protein as MOR-1 itself, but under the control of the new exon 11 promoter. Three
      variants in which exon 11 is translated have been identified within the brain,
      including MOR-1G, MOR-1M and MOR-1N. The present paper defines
      immunohistochemically the distribution of these variants using an exon 11
      specific antiserum. The expression of exon 11-like immunoreactivity (-LI) was
      seen primarily in the olfactory tubercle, caudate-putamen, globus pallidus and
      substantia nigra. We did not observe exon 11-LI in a number of regions expressing
      MOR-1. Within the caudate-putamen, the general pattern of labeling was diffuse,
      in contrast to the pattern seen with an exon 4-generated antiserum that labels
      MOR-1 itself. However, we did observe in the caudate-putamen co-expression of
      exon 4- and exon 11-LI in cells that were apposed to dopaminergic terminals.
      These results provide new insights regarding the potential physiological
      significance of these exon 11-containing variants.

PMID- 15262333
TI  - P2Y receptor expression on astrocytes in the nucleus accumbens of rats.
AB  - The expression of purinoceptor (P2)Y-subtypes on astrocytes in vivo under
      physiological conditions and after stab wound injury was investigated. Reverse
      transcriptase-polymerase chain reaction with specific primers for the receptor
      subtypes P2Y1,2,4,6,12 in tissue extracts of the nucleus accumbens of untreated
      rats revealed the presence of all P2Y receptor mRNAs investigated. Double
      immunofluorescence visualized with laser scanning microscopy indicated the
      expression of the P2Y1,4 receptors on glial fibrillary acidic protein (GFAP)
      labeled astrocytes under physiological conditions. After stab wound injury the
      additional expression of the P2Y2 and P2Y6 receptors, and an up-regulation of the
      P2Y1,4 receptor-labeling on astrocytic cell bodies and/or processes was observed.
      Astrocytes of cortical, in contrast to accumbal areas exhibited P2Y1,2,4,6
      receptor-immunoreactivity (IR) under control conditions, which was up-regulated
      after stab would injury. Labeling for the P2Y12 receptor was not observed on GFAP
      positive cortical and accumbal astrocytes under any of the conditions used. For
      the first time, the co-localization of different P2 receptor-subtypes (e.g. P2Y1
      and P2X3) on the same astrocyte was shown immunocytochemically. The up-regulation
      of P2Y1 receptor-IR on astrocytes and non-glial cells after mechanical injury
      could be facilitated by microinfusion of the P2Y1,12,13 receptor agonist
      adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS). Proliferative changes after
      ADPbetaS-microinjection were characterized by means of double-staining with
      antibodies against GFAP and 5-bromo-2'-deoxyuridine. The non-selective P2
      receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, the
      P2Y1 receptor antagonist N6-methyl-2'-deoxyadenosine 3',5'-bisphosphate and the
      P2Y1 receptor-antibody itself inhibited the agonist-induced effects. The data
      indicate the region-specific presence of P2Y receptors on astrocytes in vivo and
      their up-regulation after injury as well as the co-localization of P2X and P2Y
      receptor-subtypes on the same astrocyte. The dominant role of P2Y1 receptors in
      proliferation and the additional stimulation of non-P2Y1 receptors has been
      demonstrated in vivo suggesting the involvement of this receptor-type in the
      gliotic response under physiological and pathological conditions.

PMID- 15262334
TI  - The strong inhibition of triosephosphate isomerase by the natural beta-carbolines
      may explain their neurotoxic actions.
AB  - The natural beta-carbolines (BC) closely resemble the neurotoxin 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) in structure. The N-methylated beta
      carbolinium ions (BC+) are potent inhibitors of mitochondrial respiration and are
      nigrostriatal neurotoxins. Utilizing [3H]BC, we have identified several proteins
      to which BC binds with high affinity (e.g. the chaperone member glucose regulated
      protein 78, the enzyme carboxylesterase, the cytochrome P450 2E1, the enzyme
      monoamine oxidase B and a small G-protein of the Rho subfamily). In the present
      study we isolated a protein from bovine brain to which [3H]BC binds with high
      affinity and identified it being the enzyme triosephosphate isomerase (TPI; EC
      5.3.1.1.). 2,9-Dimethyl-BC+ was the most potent inhibitor of TPI, clearly more
      potent than the known inhibitors. TPI deficiency is a rare disorder in humans
      characterized by a severe progressive extrapyramidal course. Thus, TPI inhibition
      could contribute to neurodegeneration observed after injection of BCs into
      substantia nigra. Furthermore, the findings fit into the hypothesis of BCs as
      endogenous toxins responsible for neurodegeneration.

PMID- 15262335
TI  - Differential expression of calcium channels in sympathetic and parasympathetic
      preganglionic inputs to neurons in paracervical ganglia of guinea-pigs.
AB  - Neurons in pelvic ganglia receive nicotinic excitatory post-synaptic potentials
      (EPSPs) from sacral preganglionic neurons via the pelvic nerve, lumbar
      preganglionic neurons via the hypogastric nerve or both. We tested the effect of
      a range of calcium channel antagonists on EPSPs evoked in paracervical ganglia of
      female guinea-pigs after pelvic or hypogastric nerve stimulation. omega-Conotoxin
      GVIA (CTX GVIA, 100 nM) or the novel N-type calcium channel antagonist, CTX CVID
      (100 nM) reduced the amplitude of EPSPs evoked after pelvic nerve stimulation by
      50-75% but had no effect on EPSPs evoked by hypogastric nerve stimulation.
      Combined addition of CTX GVIA and CTX CVID was no more effective than either
      antagonist alone. EPSPs evoked by stimulating either nerve trunk were not
      inhibited by the P/Q calcium channel antagonist, omega-agatoxin IVA (100 nM), nor
      the L-type calcium channel antagonist, nifedipine (30 microM). SNX 482 (300 nM),
      an antagonist at some R-type calcium channels, inhibited EPSPs after hypogastric
      nerve stimulation by 20% but had little effect on EPSPs after pelvic nerve
      stimulation. Amiloride (100 microM) inhibited EPSPs after stimulation of either
      trunk by 40%, while nickel (100 microM) was ineffective. CTX GVIA or CTX CVID
      (100 nM) also slowed the rate of action potential repolarization and reduced
      afterhyperpolarization amplitude in paracervical neurons. Thus, release of
      transmitter from the terminals of sacral preganglionic neurons is largely
      dependent on calcium influx through N-type calcium channels, although an unknown
      calcium channel which is resistant to selective antagonists also contributes to
      release. Release of transmitter from lumbar preganglionic neurons does not
      require calcium entry through either conventional N-type calcium channels or the
      variant CTX CVID-sensitive N-type calcium channel and seems to be mediated
      largely by a novel calcium channel.

PMID- 15262336
TI  - Neurokinin-1 receptors in the rat nucleus tractus solitarius: pre- and
      postsynaptic modulation of glutamate and GABA release.
AB  - Neurokinins such as substance P and neurokinin A have long been thought to act as
      neurotransmitters or modulators in the nucleus tractus solitarius. However, the
      role and location of the receptors for these peptides have remained unclear. We
      examined the consequences of activation of the neurokinin-1 (NK1) receptor
      subtype in the rat nucleus tractus solitarius using whole-cell patch clamp
      recordings in brain slices. Application of delta-Ala-Phe-Phe-Pro-MeLeu-D
      Pro[spiro-gamma-lactam]-Leu-Trp-NH2 (a specific NK1 agonist) or neurokinin A
      resulted in depolarization, evident as a slow inward current, mediated by direct
      postsynaptic NK1 receptor activation. The effect was conserved in the presence of
      tetrodotoxin, and protein kinase C-dependent since it was blocked by 2-[1-(3
      dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide, a specific protein
      kinase C inhibitor. In addition, an increase in the frequency and amplitude of
      spontaneous excitatory postsynaptic currents was observed, reflecting increased
      glutamate release induced by NK1 receptor activation. This effect was abolished
      by tetrodotoxin, suggesting that it resulted from increased firing in afferent
      neurons, subsequent to somatodendritic excitation via NK1 receptors. Furthermore,
      spontaneous inhibitory postsynaptic currents were increased in frequency and
      amplitude showing that GABA release was promoted by NK1 receptor activation.
      However, amplitude of miniature inhibitory postsynaptic currents was unaltered by
      NK1 receptor activation, but the increase in frequency persisted. These findings
      suggest that NK1 receptors are located on presynaptic terminals as well as at
      somatodendritic sites of GABAergic neurons. The increase in GABA release was also
      shown to be protein kinase C-dependent. The data presented here show NK1
      receptors in the rat nucleus tractus solitarius are present both excitatory and
      inhibitory neurons. Activation of these receptors can result in increases in
      release of both GABA and glutamate, suggesting a crucial modulatory role for NK1
      receptors in the rat nucleus tractus solitarius.

PMID- 15262337
TI  - Delivery of insulin-like growth factor-I to the rat brain and spinal cord along
      olfactory and trigeminal pathways following intranasal administration.
AB  - We investigated the CNS delivery of insulin-like growth factor-I (IGF-I), a 7.65
      kDa protein neurotrophic factor, following intranasal administration and the
      possible pathways and mechanisms underlying transport from the nasal passages to
      the CNS. Anesthetized adult male Sprague-Dawley rats were given [125I]-IGF-I
      intranasally or intravenously and then killed by perfusion-fixation within 30
      min. Other animals were killed following cisternal puncture and withdrawal of
      cerebrospinal fluid (CSF) or intranasal administration of unlabeled IGF-I or
      vehicle. Both gamma counting of microdissected tissue and high resolution
      phosphor imaging of tissue sections showed that the tissue concentrations and
      distribution following intranasal administration were consistent with two routes
      of rapid entry into the CNS: one associated with the peripheral olfactory system
      connecting the nasal passages with the olfactory bulbs and rostral brain regions
      (e.g. anterior olfactory nucleus and frontal cortex) and the other associated
      with the peripheral trigeminal system connecting the nasal passages with
      brainstem and spinal cord regions. Intranasal administration of [125I]-IGF-I also
      targeted the deep cervical lymph nodes, consistent with their possible role in
      lymphatic drainage of both the nasal passages and the CNS. Cisternal CSF did not
      contain [125I]-IGF-I following intranasal administration. Intravenous [125I]-IGF
      I resulted in blood and peripheral tissue exposure similar to that seen following
      intranasal administration but CNS concentrations were significantly lower.
      Finally, delivery of IGF-I into the CNS activated IGF-I signaling pathways,
      confirming some portion of the IGF-I that reached CNS target sites was
      functionally intact. The results suggest intranasally delivered IGF-I can bypass
      the blood-brain barrier via olfactory- and trigeminal-associated extracellular
      pathways to rapidly elicit biological effects at multiple sites within the brain
      and spinal cord.

PMID- 15262338
TI  - Contrasting effects of mu opioid receptor and delta opioid receptor deletion upon
      the behavioral and neurochemical effects of cocaine.
AB  - Conventional brain microdialysis was used to assess basal and cocaine-induced
      dopamine (DA) levels in the nucleus accumbens of wildtype (WT) C57BL/6J mice and
      mice with constitutive deletion of ether mu- or delta-opioid receptors (MOR or
      DOR knockout [KO], respectively). Locomotor activity was assessed in these same
      animals. Basal locomotor activity of DOR KO was elevated relative to MOR KO, but
      did not differ from that of WT mice. DOR mice, but not WT or MOR KO, exhibited a
      significant increase in activity in response to an injection of saline. The acute
      administration of cocaine produced a dose-related increase in locomotor activity
      in the three genotypes. The locomotor activating effects of a low dose (10 mg/kg)
      of cocaine were enhanced in DOR KO mice whereas the locomotor activating effects
      of both a low and higher (20 mg/kg) dose of cocaine were reduced in MOR KO
      animals. Microdialysis studies revealed no difference between genotypes in basal
      DA levels. Acute administration of cocaine, but not saline, increased DA levels
      in WT and KO animals. Paradoxically, however, the magnitude of this effect was
      smaller in DOR KO as compared with that in either WT or MOR KO. These data
      indicate that constitutive deletion of either MOR or DOR results in contrasting
      effects upon responsiveness to cocaine, which is consistent with the distinct
      phenotypes previously described for these mutants.

PMID- 15262339
TI  - Involvement of adenosinergic A1 systems in the occurrence of respiratory
      perturbations encountered in newborns following an in utero caffeine exposure. a
      study on brainstem-spinal cord preparations isolated from newborn rats.
AB  - Involvement of adenosinergic A1 systems in the occurrence of respiratory
      perturbations encountered in newborns following an in utero caffeine exposure has
      been investigated on pontomedullary-spinal cord, caudal pons-medullary-spinal
      cord and medullary-spinal cord preparations isolated from newborn rats. According
      to the drinking fluid of dams (tap water or 0.02% caffeine), two groups of
      preparations were distinguished, no-caffeine and caffeine. In the no-caffeine
      group, adenosine A1 receptor activation induces a decrease in respiratory
      frequency (Rf) in caudal pons-medullary-spinal cord and medullary-spinal cord
      preparations whereas, in presence of the rostral pons, an increase is observed. A
      parallel Fos detection indicates that this discrepancy may be due to the
      excitatory action of the medial parabrachial nucleus at the rostral pontine level
      that surpasses inhibitory influence of the adenosine A1 receptor activation at
      the medullary level particularly in the ventrolateral reticular nucleus of the
      medulla. In caffeine group, an increase in the baseline Rf in presence of the
      pons and no change in medullary-spinal cord preparations have been observed.
      Depending on Fos detection, we assume that the medial parabrachial nucleus is the
      main region involved in the exaggeration of Rf. Moreover, adenosine A1 receptor
      activation was modified by in utero caffeine exposure with an overcharge of the
      Rf increase in pontomedullary-spinal cord preparations and an exaggeration of the
      Rf decrease in medullary-spinal cord preparations. Based on Fos detection, we
      link the overcharge in Rf of pontomedullary spinal cord preparations to an
      increase in the medial parabrachial nucleus neuronal activity. Similarly,
      exaggeration of Rf decrease observed without the pons is linked with a decrease
      in activity of the ventrolateral reticular neurons. This study brings evidence
      for the involvement of adenosinergic A1 systems in the occurrence of respiratory
      perturbations in newborns following in utero caffeine exposure and the importance
      of rostral pons in the adenosinergic A1 modulation of the respiratory control.

PMID- 15262340
TI  - Orexins/hypocretins cause sharp wave- and theta-related synaptic plasticity in
      the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic
      signaling.
AB  - Orexins (OX), also called hypocretins, are bioactive peptides secreted from
      glucose-sensitive neurons in the lateral hypothalamus linking appetite, arousal
      and neuroendocrine-autonomic control. Here, OX-A was found to cause a slow-onset
      long-term potentiation of synaptic transmission (LTPOX) in the hippocampus of
      young adult mice. LTPOX was induced at Schaffer collateral-CA1 but not mossy
      fiber-CA3 synapses, and required transient sharp wave-concurrent population field
      burst activity generated by the autoassociative CA3 network. Exogenous long theta
      frequency stimulation of Schaffer collateral axons erased LTPOX in intact
      hippocampal slices but not mini slices devoid of the CA3 region. Pharmacological
      analysis revealed that LTPOX requires co-activation of ionotropic and
      metabotropic glutamatergic, GABAergic, as well as noradrenergic and cholinergic
      receptors. Together these data indicate that OX-A induces a state-dependent
      metaplasticity in the CA1 region associated with sharp-wave and theta rhythm
      activity as well as glutamatergic, GABAergic, aminergic, and cholinergic
      transmission. Thus, orexins not only regulate arousal threshold and body weight
      but also threshold and weight of synaptic connectivity, providing a molecular
      prerequisite for homeostatic and behavioral state-dependent control of neuronal
      plasticity and presumably memory functions.

PMID- 15262341
TI  - Dark pulse resetting of the suprachiasmatic clock in Syrian hamsters: behavioral
      phase-shifts and clock gene expression.
AB  - In mammals, the circadian clock in the suprachiasmatic nuclei (SCN) is mainly
      synchronized to photic cues provided by the daily light/dark cycle. Phase-shifts
      produced by light exposure during the night are correlated with rapid induction
      of two clock genes, Per1 and Per2, in the SCN. Nonphotic stimuli such as
      behavioral and pharmacological cues, when presented during the subjective day,
      induce behavioral phase-advances and a down-regulation of Per1 and Per2
      expression in the SCN. When applied during the subjective day, dark pulses in
      continuous light also produce phase-advances. These phase-shifting effects have
      been interpreted as reflecting either a photic image mirror, nonphotic cues, or a
      combination of both. Here we evaluated in Syrian hamsters housed in constant
      light how dark pulses applied in late subjective day affect levels of Per1, Per2
      and Cry1 mRNA. Four-hour dark pulses with no access to a wheel produced 1.2+/-0.4
      h phase-advances of locomotor activity rhythm while control manipulation induced
      non-significant shifts (0.1+/-0.2 h). Dark pulses transiently down-regulated Per1
      and Per2 mRNA levels in the SCN by 40 and 20% respectively, while the levels of
      Cry1 mRNA remained unaffected. In behaviorally split hamsters in which Per
      oscillations were asymmetric between the left and right sides of the SCN, dark
      pulses reduced Per expression in the half-SCN with high Per. This study shows
      that exposure during the late subjective day to dark pulses independent of wheel
      running have nonphotic-like effects on the SCN clock at both behavioral and
      molecular levels.

PMID- 15262344
TI  - Insulin resistance and metformin in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with widespread
      systemic manifestations affecting 5-10% of women of reproductive age. The
      accompanying insulin resistance and hypeinsulinemia mark this syndrome as a
      prediabetic state, with high incidence of impaired glucose tolerance, gestational
      diabetes, and overt diabetes. Other metabolic and biochemical changes, such as
      hypertension and dyslipidemia, increase the risk of cardiovascular disease.
      Fertility may also be impaired due to anovulation, impaired implantation, and
      higher rates of spontaneous abortions. All of these effects may also be related
      to hyperinsulinemia. Metformin, as insulin-sensitizing drug, is being evaluated
      for its potential long-term disease-modifying effect, such as prevention of
      diabetes. Its use may also help restore spontaneous ovulation and improve
      menstrual cyclicity, improve the success rate of induction of ovulation with
      clomiphene citrate and FSH, and decrease the high rate of ovarian
      hyperstimulation and early pregnancy loss. Nevertheless, these new exiting
      potential benefits of metformin should be evaluated in large randomized
      controlled studies, and clinicians must counsel women appropriately before the
      initiation of metformin therapy.

PMID- 15262342
TI  - Bcl-2 immunoreactive neurons are differentially distributed in subregions of the
      amygdala and hippocampus of the adult macaque.
AB  - The amygdala and hippocampus are key limbic structures of the temporal lobe, and
      are implicated in the pathology of mood disorders. Bcl-2, an intracellular
      protein, has recently been identified in the primate amygdala and hippocampus,
      and is now recognized as an intracellular target of mood stabilizing drugs.
      However, there are few data on the cellular phenotypes of bcl-2-expressing cells,
      or their distribution in specific subregions of the amygdala and hippocampus. We
      used a number of histochemical markers to define specific subregions of the
      primate amygdala and hippocampus, and examined phenotype-specific distributions
      of bcl-2 immunoreactive cells within each subregion. Immature-appearing bcl-2
      labeled neurons, which co-contain class III beta-tubulin immunoreactivity, are
      found in distinct subregions in each structure. In the amygdala, bcl-2 positive
      neurons with an immature morphology are densely distributed in the paralaminar
      nucleus and intercalated cell islands, the parvicellular basal nucleus, and the
      ventral periamygdaloid cortex and amygdalohippocampal area. In the hippocampus,
      immature-appearing bcl-2-labeled cells are confined to the polymorph layer
      (subgranular zone), and base of the granule cell layer in the dentate gyrus. Well
      differentiated neurons also express bcl-2. In the amygdala, labeled cells with
      mature phenotypes are concentrated in the parvicellular basal nucleus, the
      accessory basal nucleus, and the periamygdaloid cortex. The medial nucleus and
      central extended amygdala also contain many well-differentiated bcl-2 positive
      cells. In the hippocampus, the dentate gyrus and Ammon's horn contain many bcl-2
      immunoreactive nonpyramidal cells. These are preferentially distributed in the
      rostral hippocampus. CA3 and CA2 contain relatively higher concentrations of bcl
      2-labeled cells than CA1 and the subiculum. Bcl-2 is thus important in intrinsic
      circuitry of the hippocampus, and in amygdaloid subregions modulated by the
      hippocampus. In addition, the extended amygdala, a key amygdaloid output, is
      richly endowed with bcl-2 positive cells. This distribution suggests a role for
      bcl-2 in circuits mediating emotional learning and memory which may be targets of
      mood stabilizing drugs.

PMID- 15262345
TI  - Pathophysiology of preeclampsia: links with implantation disorders.
AB  - The phenomenon of implantation anchors the embryo into the uterine wall and
      produces a hemochorial placenta that maintains the pregnancy and fetal growth.
      Implantation and placentation are intimately linked and cannot be dissociated
      either in time or in space. Preeclampsia is characterized by hypertension and
      proteinuria. It is secondary to an anomaly of the invasion of the uterine spiral
      arteries by extra-villous cytotrophoblast cells, associated with local
      disruptions of vascular tone, of immunological balance and inflammatory status,
      and sometimes with genetic predispositions. Preeclampsia is a disease of early
      pregnancy, a form of incomplete spontaneous abortion, but is expressed late in
      pregnancy. Aspirin may play a favorable role in implantation which is related to
      the genesis of preeclampsia and some cases of intra-uterine growth restriction.
      The most important points in obtaining a preventive effect from low-dose aspirin
      during the pregnancy are early treatment (before 13 weeks of gestation) and the
      prescription of a sufficient dose (more than 100 mg per day).

PMID- 15262346
TI  - Efficient prematurity prevention is possible by pH-self measurement and immediate
      therapy of threatening ascending infection.
AB  - In two prospective investigations, the effectiveness of the self care programme
      for prematurity prevention, developed by Saling, was investigated. Pregnant women
      in Erfurt have been offered to perform self measurements of their vaginal pH by
      means of test gloves twice a week in order to screen for any disturbances in the
      vaginal milieu. The women were instructed to see their physician immediately, if
      abnormal pH > or = 4.7 or other risk factors were present, in order to get them
      confirmed and to start lactobacillus acidophilus therapy or in case of bacterial
      vaginosis to treat with clindamycin cream i. vag. Patients who were not
      interested in the programme served as a control group. Seventy-three out of 381
      women in the intervention group have been identified as risk cases. Fifty-eight
      of them were treated with a lactobacillus preparation, and 24 with clindamycin
      cream, three patients refused to have any therapy. In this study, the prematurity
      rate was 8.1% in the self measurement/intervention group versus 12.3% in the
      control group (P < 0.05, n = 2341). 0.3% versus 3.3% of the neonates belonged to
      the group of very early prematures with a gestational age of <32 + 0 (P < 0.01).
      PROM was registered in 22.8% versus 30.8% (P < 0.001), respectively. Starting 1
      March 2000, a similar statewide pH screening programme was initiated in order to
      reduce prematurity in the State of Thuringia. According to the study design, a
      significant decrease of prematurity was hypothetically expected for the second
      half of 2000. In Erfurt, an overall decrease of prematurity from 7.68 to 6.81%
      and a reduction of cases < or = 32 weeks from 3.22 to 2.39% was observed.
      Premature rupture of membranes was seen in 19 versus 0 pregnancies with early
      prematurity (n = 1600). Data from 16,276 women are available for the state of
      Thuringia. On this basis, a significant reduction of early prematurity from 1.58
      to 0.99% was seen, respectively (P < 0.001). Comparing low birthweights a
      significant reduction of cases was achieved as well in all groups. On the basis
      of the data obtained we recommend the extension of the campaign in whole of
      Germany.

PMID- 15262347
TI  - Effects of betamethasone and thyroid releasing hormone on fetal lung maturation:
      an experimental and morphometric study.
AB  - OBJECTIVE: To determine the effects of betamethasone and thyroid releasing
      hormone (TRH) on morphologic fetal rabbit lung maturation when administered
      separately and in combination. MATERIAL AND METHODS: Twenty-five pregnant rabbits
      were divided into five groups. Study groups were as follows: TRH or betamethasone
      alone (between 24 and 27th days of gestation), TRH + betamethasone or
      betamethasone + TRH (second dose of drugs were added in the last 2 days), and the
      control. The pregnancies were terminated on the 27th day of gestation. Weights
      and volumes of the fetal lungs were determined and the results were compared.
      RESULTS: Mean lung weights in all treatment groups were significantly heavier
      than controls (P < 0.05). The differences between mean lung weights of TRH alone,
      TRH + betamethasone, and betamethasone alone groups were not statistically
      significant (P > 0.05), but the mean lung weight of betamethasone + TRH group was
      significantly lower than the other treatment groups (P < 0.05). Mean lung volume
      of TRH alone group was significantly higher than control group; however, there
      were no significant differences between other treatment groups and the control.
      No correlation was found between the lung weights and volumes in all groups (r =
      0.1, P > 0.05). CONCLUSION: Only TRH alone treatment produced a significant
      increase in both fetal lung volume and weight compared to the control group.
      Administering TRH alone can lead to increased lung maturation. Combining TRH to
      corticosteroid treatment significantly decreased mean fetal lung weight, instead
      of an increase. According to these results combined used of these two substances
      probably counteract each others effect, instead of having a synergism.

PMID- 15262348
TI  - Infectious and inflammatory mechanisms in preterm birth and cerebral palsy.
AB  - OBJECTIVE: In a thesis examine infectious and inflammatory mechanisms involved in
      preterm birth and cerebral palsy. STUDY DESIGN: Four cross-sectional studies and
      a case control study. RESULTS: Microbial invasion of the amniotic cavity and
      inflammation in this population of Swedish women in preterm labor and preterm
      prelabor rupture of membranes was similar to that reported in data from
      populations with a higher incidence of preterm birth. Our data support an
      association between antenatal infection/inflammation and cerebral palsy.
      CONCLUSIONS: Infectious and inflammatory mechanisms are involved in preterm birth
      and cerebral palsy in a population with low incidence of preterm birth.

PMID- 15262349
TI  - Pregnancy in maltese drug-abusers: a socio-biological study.
AB  - The use of illicit drugs has increased disturbingly in the last decades, this
      increase being reflected by an increase in the number of female drug abusers who
      present in the pregnant state. A total of 47 cases of current or past heroine
      abuse (0.24% of total maternities) were delivered at the Karin Grech Maternity
      Unit of St. Luke's Teaching Hospital in Malta. The socio-biological
      characteristics of these women were assessed and compared to similar parameters
      in the remaining pregnant population. These women have been shown to be generally
      of a younger age <25 years and are generally unmarried. The women tend to seek
      antenatal care late in pregnancy. Their associated medical problems include
      Hepatitis C infection. There also appeared to be a statistically increased
      predisposition to pre-existing diabetes. There did not appear to be any
      statistically significant increased risks to the infant, though there may have
      been a greater predisposition to low birth weight and prematurity.

PMID- 15262350
TI  - Postpartum haemorrhage in nulliparous women: incidence and risk factors in low
      and high risk women. A Dutch population-based cohort study on standard (> or =
      500 ml) and severe (> or = 1000 ml) postpartum haemorrhage.
AB  - OBJECTIVE: To determine the incidence and risk factors for standard and severe
      postpartum haemorrhage (PPH) in vaginally delivering nulliparous women, before
      and after risk stratification. STUDY DESIGN: A population-based cohort study in
      an unselected cohort nulliparous women (N = 3464) in 'The Zaanstreek' district,
      The Netherlands. Risk stratification is part of routine care, where midwives
      cover all obstetrical care for women with low risk pregnancies. RESULTS: The
      incidence of standard PPH (> or = 500 ml) and severe PPH (> or = 1000 ml) were 19
      and 4.2%, respectively. A retained placenta occurred in 1.8%. These data show
      consistently slightly higher values as compared to studies in literature. The
      most important risk factors for standard and severe PPH were related to an
      abnormal third stage of labour-third stage > or = 30 min and retained placenta
      (in severe PPH: odds ratio (OR) 14.1, 95% confidence interval (CI) 10.4-19.1).
      High birth weight and perineal damage were less important, but independent,
      significant risk factors. In the low risk group (N = 1416), incidence of severe
      PPH was 4.0%. Independent risk factors for severe PPH were third stage > or = 30
      min (incidence 7.1%, OR 3.6) and retained placenta (incidence 1.2%, OR 21.6). In
      25% of the women with a prolonged third stage (> or = 30 min), third stage was
      complicated due to retained placenta and/or severe PPH (1.8% of the low risk
      group). CONCLUSIONS: The incidence of PPH in nulliparous women in this cohort was
      on average higher than published data, while the most important risk factors for
      standard and severe PPH, even after risk stratification, were the same. A
      prolonged third stage of labour has to be considered as abnormal, requiring
      specific action.

PMID- 15262352
TI  - Parental employment status and neural-tube defects and folic acid/multivitamin
      supplementation in Hungary.
AB  - OBJECTIVE: To study the role of parental employment status as indicator of socio
      economic status (SES) in the origin of neural-tube defect (NTD) and in the use of
      periconceptional folic acid/multivitamin supplementation. MATERIALS AND METHODS:
      One thousand two hundred and two cases with neural-tube defects, 38,151
      population controls without any defects and 22,475 patient controls with other
      defects were compared in the population-based data set of the Hungarian case
      control surveillance of congenital abnormalities, 1980-1996. RESULTS: The
      proportion of professionals was lower, while the proportion of semi- and
      unskilled workers was higher in the neural-tube defect group compared with the
      population control group. However, the comparison of neural-tube defect and
      patient control groups showed a lower socio-economic status in the patient
      control group. In addition, the socio-economic status of fathers in the neural
      tube defect group seemed to be better than in the population and patient control
      groups. The higher periconceptional folic acid supplementation and the higher use
      of multivitamins during pregnancy occurred in the professional and managerial
      categories in all the three study groups. CONCLUSION: The occurrence of neural
      tube defect shows a slight socio-economic dependence in the mothers at the
      comparison with population control group, however, patient control group had the
      lowest socio-economic status. The higher maternal education goes together with a
      higher proportion of periconceptional folic acid supplementation.

PMID- 15262351
TI  - Awareness of the use of folic acid to prevent neural tube defects in a
      Mediterranean area.
AB  - OBJECTIVES: The risk of neural tube defects (NTDs) is decreased in women who take
      folic acid during the periconceptional period. The main objective of our study
      was to evaluate the awareness of the need for folic acid supplementation and also
      the actual intake during the periconceptional period to prevent neural tube
      defects in a Mediterranean area. STUDY DESIGN: A retrospective study was
      performed from 1 July to 30 November 2000. One thousand consecutive women who
      delivered in our hospital were interviewed during the immediate postpartum period
      about their knowledge of neural tube defects and folic acid intake before and
      during pregnancy. RESULTS: Most women (85.7%) referred not having been
      specifically informed about the need to take folic acid to prevent neural tube
      defects although approximately half of the women (50.6%) were in fact, aware of
      the need for folic acid intake. Eight percent (8.1%) of the women took folic acid
      before conception but only 6.9% did so during the effective period from 4 weeks
      before conception to 4 weeks after conception. Logistic regression analysis
      showed that awareness of the need to take folic acid together with having had
      preconceptional counselling and knowledge of NTDs were the strongest variables
      related to the fact of having taken folic acid during the correct period.
      CONCLUSIONS: Although the population is aware of the need to take folic acid, the
      real impact of the present recommendations is almost negligible. Information in
      primary care and preconceptional counselling to specifically inform patients
      about the need to take folic acid to prevent NTDs seem to be crucial to improve
      the final intake of folic acid during the protective period.

PMID- 15262353
TI  - Screening for trisomy 21 in Flanders: a 10 years review of 40.490 pregnancies
      screened by maternal serum.
AB  - OBJECTIVE: To evaluate maternal serum screening for trisomy 21 (MSS) in Flanders
      between 1992 and 2002. STUDY DESIGN: Data of a large database on the results of
      MSS, nuchal translucency (NT) and pregnancy outcome were analysed
      retrospectively. RESULTS: Despite an excellent performance of second trimester
      MSS at a maternal age > or = 35 years (94.4% detection rate (DR) of trisomy 21 at
      a false positive rate (FPR) of 22.4%), the proportion of patients above 35 years
      of age in the study population was significantly lower than in the Flemish
      general pregnant population (5.5% versus 8.9%, P < 0.001). In the population
      screened by MSS and NT, the DR of second trimester MSS at a 5% FPR was 44.4%,
      which was lower than 66.6% in the population screened by MSS without NT. When
      nine trisomy 21-affected pregnancies were compared to 3265 normal pregnancies,
      the mean NT-MoM values were not significantly different (1.16 +/- 0.89 versus
      1.00 +/- 0.46, P > 0.05). Both the findings comply to a sequential screening
      practice where second trimester MSS is only performed after a normal measurement
      of NT in the first trimester. CONCLUSION: In Flanders, the uptake of second
      trimester maternal serum screening is low in women aged 35 years or more. Its
      screening performance decreased after the introduction of sequential screening.

PMID- 15262354
TI  - Effect of estradiol valerate and levonorgestrel on vaginal health.
AB  - OBJECTIVES: To evaluate the effect of the combined hormone replacement therapy
      (HRT) estradiol valerate/levonorgestrel on vaginal symptoms, vaginal health
      index, vaginal pH, and vaginal cytology. STUDY DESIGN: A prospective, open-label
      study involving 32 postmenopausal women was performed in Ramathibodi Hospital,
      Mahidol University, Bangkok, Thailand. All the subjects received sequential oral
      estrogen-progestogen hormone replacement therapy, which contains 2 mg estradiol
      valerate and 0.15 mg levonorgestrel, for 6 months. The results in terms of
      vaginal health index, vaginal pH, and vaginal cytology before and after treatment
      were analyzed. RESULTS: The mean age of these postmenopausal women was 52.56 +/-
      3.33 years (range: 46-60 years). The mean time since the last menstrual period
      was 3.41 +/- 2.95 years (range: 1-15 years). The vaginal health index, which
      indicates vaginal health by means of scores for vaginal moistness, vaginal fluid
      volume, vaginal elasticity, vaginal mucosa, and vaginal pH rose significantly in
      all the women. The mean vaginal pH became significantly lower. The vaginal
      cytology showed an estrogenic effect on the karyopyknotic index (KPI) and the
      maturation value (MV) after 3 and 6 months of treatment. CONCLUSION: During
      estradiol valerate and levonorgestrel treatment, there were demonstrable
      improvements in the objective signs of vaginal atrophy: atrophic vaginal
      epithelium became thicker and vaginal pH lower, and the morphology of the vaginal
      cells was better.

PMID- 15262355
TI  - Follicular fluid concentrations of vascular endothelial growth factor, inhibin A
      and inhibin B in IVF cycles: are they markers for ovarian response and pregnancy
      outcome?
AB  - OBJECTIVE(S): The aim of this study was to measure concentrations of vascular
      endothelial growth factor (VEGF), inhibin A and inhibin B in follicular fluid
      (FF) of women undergoing to in vitro fertilization (IVF) cycles and to determine
      their relationship with ovarian response and pregnancy. STUDY DESIGN: Follicular
      fluid was collected from 58 patients undergoing oocyte retrieval for IVF.
      Ovulation was induced with GnRH analogues and gonadotropins. Follicular fluids of
      mature follicles (>17 mm) were aspirated and pooled for each patient. Follicular
      fluid steroid hormone levels (E2, P) and VEGF, inhibin A, inhibin B
      concentrations were studied. The serum levels of E2, P and VEGF were also
      assessed on the day of the oocyte retrieval. These parameters and characteristics
      of the cycles were compared between the pregnant (group 1) and non pregnant
      (group 2) patients. RESULTS: The serum and FF VEGF levels were found to be
      significantly lower in the group in whom the pregnancy was achieved (P < 0.001).
      The FF inhibin A and FF inhibin B were found to be significantly higher in
      pregnant group (P < 0.001). However, age, day 3 FSH, dosage of gonadotropin
      administered, fertilization rate, sperm count, motile and morphologically normal
      sperm percentage were not significantly different in the two groups. There was an
      negative correlation between VEGF and number of follicles, number of oocytes, FF
      inhibin A, FF inhibin B. The number of oocytes retrieved, the fertilization rate
      were positively correlated with FF inhibin B and FF inhibin A. CONCLUSION: This
      study demonstrated that decreased FF VEGF, serum VEGF and elevated FF inhibin A
      and B are associated with better ovarian response and high pregnancy rate.

PMID- 15262356
TI  - The association of bone mineral density with insulin resistance in patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of the study was to compare the bone mineral density (BMD)
      measurements between the patients with polycystic ovary syndrome (PCOS) and age
      and the body mass index (BMI) matched healthy controls, and to examine whether
      insulin resistance was associated with BMD. STUDY DESIGN: Twenty-nine consecutive
      patients with PCOS and seventeen, age and BMI matched healthy control women were
      included in the study. Blood samples were obtained for follicle stimulating
      hormone, luteinizing hormone, estradiol, dehydroepiandrosterone-sulfate, 17
      hydroxy-progesterone, free testosterone, sex hormone binding globulin, insulin,
      and glucose levels and BMD measurements were performed for total body, lumbar
      spine (L2-L4), and femoral neck for each participant. Insulin resistance was
      estimated by fasting insulin level, fasting glucose/insulin ratio and 75 g of
      glucose tolerance test for 2 h. Differences between the groups were analyzed by
      Student's t-test and Mann-Whitney U-test where appropriate. Correlation analysis
      between the parameters concerning insulin resistance and BMD measurements were
      performed in patients with PCOS using Pearson's correlation coefficient (r).
      Correlation analysis was also performed between serum hormone levels and BMD
      measurements in the PCOS group. Partial correlation coefficients were calculated
      for these parameters, using age and BMI as covariates. RESULTS: Free testosterone
      and 17 hydroxy-progesterone levels were significantly high in patients with PCOS
      compared to the control women (P = 0.001 and 0.04, respectively). Fasting insulin
      was significantly higher and fasting glucose/insulin ratio was significantly
      lower in the PCOS group compared to the controls (P = 0.021 and 0.008,
      respectively). BMD measurements did not differ between the groups (P > 0.05).
      There were significant correlations between fasting insulin and total BMD (r =
      0.424, P < 0.05) and fasting glucose/insulin ratio and L2-L4 BMD (r = -0.401, P <
      0.05) after controlling for age and BMI. CONCLUSION: BMD measurements are not
      different between the patients with polycystic ovary syndrome and healthy control
      women and hyperinsulinemia, and insulin resistance might play a role in the
      preserved BMD.

PMID- 15262357
TI  - The malignant potential of endometrial polyps.
AB  - OBJECTIVES: To determine the pre-malignant and malignant potential of endometrial
      polyps and to assess whether different clinical parameters are associated with
      malignancy in the polyps. STUDY DESIGN: Four hundred and thirty consecutive cases
      of hysteroscopic diagnosis of endometrial polyp were retrieved. The medical
      records, preoperative vaginal sonography results and histopathology findings were
      reviewed. Statistical analysis was performed. RESULTS: Hysteroscopy truly
      identified endometrial polyps in 95.7% of the cases. In 11.4% cases, hyperplasia
      without atypia was found in the endometrial polyp. In 3.3 and 3.0% of women pre
      malignant or malignant conditions were found in the polyp. Older age, menopause
      status and polyps larger than 1.5 cm were associated with significant pre
      malignant or malignant changes, although the positive predictive value for
      malignancy was low. All the malignant polyps were diagnosed only in
      postmenopausal women. The presence of postmenopausal or irregular vaginal
      bleeding, was not a predictor of malignancy in the polyp. CONCLUSIONS:
      Postmenopausal women with endometrial polyps are at increased risk of malignancy
      in the polyp. Those patients, whether symptomatic or not should be evaluated by
      hysteroscopic resection of the polyps. Asymptomatic premenopausal patients with
      polyps smaller than 1.5 cm can be observed.

PMID- 15262358
TI  - Does fluid hysteroscopy increase the stage or worsen the prognosis in patients
      with endometrial cancer? A randomized controlled trial.
AB  - OBJECTIVE: To determine whether fluid hysteroscopic directed biopsies, in
      patients with endometrial cancer upstages the tumor and worsens the prognosis.
      STUDY DESIGN: Between January 1996 and September 2001, a total of 62 consecutive
      patients with endometrial cancer, treated at our institution, were randomized 3:2
      to have or not to have a fluid hysteroscopic biopsy just prior to surgery. A
      total of 38 patients underwent a hysteroscopy after the induction of anesthesia.
      All patients had pelvic washings performed, followed by a hysterectomy, bilateral
      salpingooforectomy and pelvic +/- para-aortic lymph node dissections. Only stages
      I and II endometrioid type tumors or stage IIIa, secondary to positive pelvic
      washings, were included in the study. Eight patients in the hysteroscopy group
      and four patients in the control group were excluded for various reasons.
      Patients received post-operative radiation therapy depending on the surgical
      pathological risk factors. The median follow up was 34 months. Fisher's Exact
      Test was performed to compare differences between the hysteroscopic (n = 30) and
      the control (n = 20) groups. RESULTS: We found three patients (10%) with positive
      washings in the hysteroscopic group compared to one (5%) among the controls (P =
      0.64), with a statistical power of <20%. If the differences would persist, we
      would need 588 patients in each arm to obtain a power of 80%, and reach
      definitive conclusions. The Odds Ratio (OR) of performing a hysteroscopy and
      upstaging the tumor in this study was: 2.1 95% CI (0.20-21.09). Prognostic
      variables were compared between both groups and no differences were observed. All
      patients but one (dead due to intercurrent disease), were alive and with no
      evidence of disease at the completion of the study. CONCLUSIONS: Fluid
      hysteroscopy and directed biopsies may have a small risk of upstaging early
      endometrial cancers, but does not seem to influence prognosis.

PMID- 15262359
TI  - Surgical treatment of locally progressive stage IIIB carcinoma of the cervix: use
      of the inverted "T" incision.
AB  - Stage III carcinoma of the cervix is treated usually, and often effectively, with
      the combination of radiation and chemotherapy. For tumors locally recurring,
      without evidence of distant lymphatic or hematogenous spread, the option of
      pelvic exenteration rises. The described surgical technique derives from soft
      tissue sarcoma pelvic surgery. It is a lower midline incision extending
      transversely at its lower end ("reverse T"), which improves the exposure and
      hence resectability of some of these tumors.

PMID- 15262360
TI  - Laparoscopically assisted vaginal hysterectomy for large uterus: a comparative
      study.
AB  - OBJECTIVE: To examine the safety and feasibility of laparoscopically assisted
      vaginal hysterectomy (LAVH) for uteri weighing 500 g or more as compared to uteri
      weighing less than 500 g in the management of benign gynecological diseases.
      METHOD: In this prospective comparative study, 189 women with different benign
      gynecological diseases were scheduled for laparoscopically assisted vaginal
      hysterectomy. They were divided into two groups, with uterine weight greater than
      500 g and uterine weight less than 500 g. Outcome measures for both the groups
      were studied comparatively in terms of length of operative time, amount of blood
      loss, requirement of blood transfusion and length of hospital stay. RESULTS:
      Length of operation and amount blood loss were significantly greater in the uteri
      >o r = 500 g group than in the <500 g at 91.1 +/- 28.7 min versus 77.4 +/- 26.6
      min (P < 0.01), and 570.5 +/- 503.6 ml versus 262.5 +/- 270.0 ml (P < 0.001),
      respectively. However, there was no difference in length of hospital stay and
      overall incidence of operative complications between the two groups. None of the
      women had any major complications though 17 minor complications were noted. There
      was no incidence of switching to abdominal laparatomy during the operation except
      for one patient who required "minilaparotomy" for removal of large surgical
      specimen (2400 g). Extreme intra-operative hemorrhage of more than 1000 ml
      occurred in five patients, however, they made full recovery after blood
      transfusion. Rate of blood transfusion was significantly lower in the uteri <500
      g group (4.8% versus 34.9%, (P < 0.001). CONCLUSION: This study demonstrates that
      despite the increased operating time and blood loss, LAVH can be safely performed
      for large uterus. However, surgeons need to be aware of the high risk of blood
      transfusion in these patients.

PMID- 15262361
TI  - The scope of vaginal hysterectomy.
AB  - OBJECTIVE: The study was designed to check the feasibility of the vaginal route
      as the primary route for hysterectomy. STUDY DESIGN: All patients in whom
      hysterectomy was indicated were first considered for vaginal hysterectomy unless
      this route was contraindicated. Vaginal hysterectomy (VH) was performed in 5655
      patients, and in 90.4% of these no uterine prolapse was present. The operative
      intervention required, preconditions and any complications were carefully
      studied. RESULTS: Of the 6945 cases considered, vaginal hysterectomy was possible
      in 5655 (81%). Successful simultaneous prophylactic oophorectomy or salpingo
      oophorectomy was possible, in 1510 of 1572 cases without laparoscopic assistance.
      The indications are carefully discussed, with a strong emphasis on examination
      under anaesthesia, preoperative total uterine volume and, if required,
      laparoscopic evaluation and surgeons' readiness to reduce the frequency of
      recourse to laparotomy or laparoscopic assistance. CONCLUSION: The vaginal route
      is the least invasive and most economical route for hysterectomy and should be
      the gynaecological surgeon's first choice. A uterus with a volume up to 300 cm3
      or uterine size up to 12 weeks should be dealt with vaginally, and as surgeons
      become more experienced larger uteri and also the adnexa can be approached in the
      same manner, at least as trial vaginal hysterectomy.

PMID- 15262362
TI  - Primary small cell neuroendocrine tumour of the breast.
AB  - Primary neuroendocrine carcinomas of the breast are extremely rare. Tumours can
      only be considered small cell neuroendocrine tumour of the breast if nonmammary
      sites are excluded. These tumours form a diagnostic and therapeutic challenge. We
      present our experience of small cell neuroendocrine tumour of the breast and
      discuss a review of the relevant literature.

PMID- 15262363
TI  - Nipple discharge and the value of MR imaging.
AB  - Nipple discharge is common, and is associated with a malignancy in 5-20% of
      cases. Physical examination and the colour or clarity are of importance. Cytology
      and galactography have little value in the evaluation of nipple discharge. Age is
      considered one of the most important risk factors for breast cancer. We describe
      the valuable contribution of magnetic resonance imaging in evaluating an elderly
      patient with nipple discharge where clinical and mammography examinations were
      negative.

PMID- 15262364
TI  - A case of huge enlargement of cystosarcoma phylloides of breast in pregnancy.
AB  - A case of unilateral phylloides tumor of breast with sudden enlargement during
      pregnancy has been presented with successful pregnancy outcome followed by
      complete surgical excision (simple mastectomy) in the puerperium.

PMID- 15262365
TI  - Do we have any good reason to suggest restricting the use of oral contraceptives
      in women with pre-existing Vitamin B12 deficiency?

PMID- 15262367
TI  - Serum folate and Vitamin B12 levels in women using modern oral contraceptives
      (OC) containing 20 microg ethinyl estradiol.

PMID- 15262368
TI  - Imiquimod contact pemphigus: a comment.

PMID- 15262369
TI  - Recurrent benign intracranial hypertension in pregnancy.

PMID- 15262370
TI  - Fetal holoprosencephaly with dorso-lumbar meningomyelocoel and transposition of
      great arteries in a woman with tetralogy of fallot.

PMID- 15262371
TI  - An advanced stage low grade endometrial stromal sarcoma: a therapeutic dilemma.

PMID- 15262373
TI  - Return to play for rotator cuff injuries and superior labrum anterior posterior
      (SLAP) lesions.
AB  - The shoulder is a frequently injured joint in athletes, and the most common
      injuries in active patients include instability, rotator cuff injuries, and
      superior labrum lesions. These three types of injuries often involve different
      mechanisms of injury, variable methods of surgical repair, and different
      considerations in rehabilitation and return to play. This article focuses upon
      rotator cuff injuries and superior labrum lesions, treated nonoperatively and
      operatively. Return to play with these injuries depends upon many factors
      including upon the age of the patient, the severity of the pathology,the type of
      treatment rendered, and the expectations of the patient.

PMID- 15262374
TI  - Shoulder instability: return to play.
AB  - Shoulder instability in the competitive athlete is a relatively common problem.
      The etiology of glenohumeral instability that can affect the athlete runs a wide
      spectrum, from an isolated traumatic dislocation to repeated microtrauma or
      congenital laxity. Although many athletes are able to adapt to a mild laxity that
      might only occasionally affect them, it can be much more difficult to adapt or
      return to play after a dislocation or repeated subluxation episodes. This article
      focuses on the return to play for competitive individuals after a glenohumeral
      dislocation or reconstructive surgery for shoulder instability.

PMID- 15262375
TI  - Return to sport following elbow surgery.
AB  - Although less common than injuries to the knee or shoulder, elbow injuries can be
      a substantial challenge to sports medicine providers. Many elbow problems respond
      to routine nonoperative measures including periods of activity modification and
      physical therapy, but others may ultimately require surgery. Following surgery,
      appropriate attention to rehabilitation is important to achieve optimal function.
      This article addresses some of the more common sports-related operative elbow
      pathology, basic principals of surgery (with an emphasis on techniques only where
      it may impact rehabilitation or return-to-sport decisions), and return-to-play
      decisions (including typical "targeted" time frames). The emphasis is on an
      understanding of sport-specific functional demands and the difficult assessment
      of reinjury risk following surgery.

PMID- 15262376
TI  - Return to play after lumbar spine conditions and surgeries.
AB  - Low back pain in athletes can result from a wide variety of conditions. A
      detailed history and physical examination supplemented by appropriate imaging
      studies can lead to an accurate diagnosis. The majority of cases will be self
      limiting and resolve within 6 weeks regardless of treatment, but it is important
      to be able to identify conditions that require specific treatment. The decision
      of when an athlete can return to active competition is determined by the specific
      condition, associated symptoms, and treatment provided. Most athletes can return
      to full unrestricted play after sufficient resolution of pain and restoration of
      range of motion. Athletes undergoing spinal fusion are typically restricted from
      full-contact sports.

PMID- 15262377
TI  - Return to play following surgical treatment of meniscal and chondral injuries to
      the knee.
AB  - Much has been written in the sports medicine literature regarding return to
      competition following anterior cruciate ligament reconstruction; however, little
      scientific work has been done regarding the return to competition following
      meniscal surgery or cartilage surgery. This article reviews the basic science of
      meniscal surgery and cartilage surgery in an attempt to promote rational
      rehabilitative protocols rooted in scientific investigation. A twofold approach
      is used. One approach is from a biologic standpoint; that is, when are the
      repaired tissues healed enough to withstand physiologic activity? The second
      approach is from a rehabilitative standpoint; when is the patient strong enough
      to play without recurrent injury?

PMID- 15262378
TI  - Return to play after anterior cruciate ligament reconstruction.
AB  - The goal of knee ligament reconstruction is to return the athlete to the previous
      level of function as quickly and as safely as possible. The appropriate level of
      aggressiveness in returning the athlete to sport remains controversial.
      Information in the literature regarding safe return to play has been dominated by
      the anterior cruciate ligament (ACL) reconstruction literature. The basic
      concepts that hold true for returning the ACL-reconstructed athlete to play can
      be generalized to injuries treated nonoperatively as well. This article presents
      a review of the principles of rehabilitation following knee ligament
      reconstruction, with an emphasis on criteria for return to play.

PMID- 15262379
TI  - Transient quadriplegia and return-to-play criteria.
AB  - There will always be an inherent risk to participation in contact sports.
      Appropriate education of coaches, players, and parents is important. Recurrence
      rate is high in the athlete who has experienced transient quadriplegia or any
      neck injury. The athlete and his family should be made aware of this risk.
      Counseling is even more important, both from a medical and legal standpoint, in
      the patient with underlying spinal stenosis, found either incidentally or
      following an episode of transient quadriplegia. In these situations,
      consideration of consultation with a neurologist or neurosurgeon is prudent.

PMID- 15262380
TI  - Return to play following sports-related concussion.
AB  - This article provides a review of current important issues in the management of
      athletes who have sustained a concussion during athletic competition. Recent
      research in the area of concussion management is reviewed with specific reference
      to the side line evaluation of concussion and the follow-up of the athlete during
      the recovery period. The use of neuropsychological testing in sports is also
      reviewed. A systematic protocol for the management of sports related concussion
      is presented.

PMID- 15262381
TI  - Pneumothorax and pneumomediastinum.
AB  - Pneumothorax and pneumomediastinum occur uncommonly in association with athletic
      participation. Although they are rare, when they occur they can be life
      threatening, requiring immediate diagnosis and treatment. These injuries also
      present difficult return-to-play decisions for the sports medicine physician.
      There are sparse data to help determine the incidence of these injuries in sport,
      as well as their optimal treatment. Although most sports physicians have seen
      these injuries, not many have seen enough to publish a large series discussing
      optimal management or make return-to-play recommendations.

PMID- 15262382
TI  - Cardiovascular disease in athletes.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the United States,
      resulting in increased awareness of the preventive importance of regular physical
      activity. Because athletes are considered physically fit, occurrence of sudden
      athlete death from CVD is perplexing. Regular intense physical activity can cause
      changes to the cardiovascular system that mimic known CVD processes. Therefore,
      screening of athletes for conditions that may increase risk for sudden cardiac
      death (SCD) is challenging. This article focuses on this problem, discussing the
      athlete's heart, SCD and associated CV conditions, and preparticipation
      screening. We also review recommendations of the 26th Bethesda Conference on
      determining eligibility for competition in athletes with known CV abnormalities,
      and how the recommendations relate to individual disease processes.

PMID- 15262383
TI  - Herpes gladiatorum and other skin diseases.
AB  - Musculoskeletal injury, appropriately, is the focus of time-loss from practice
      and competition. Nevertheless, skin infections are responsible for between 10%
      and 15% of time-loss injuries at the collegiate level. The risk of contagion has
      resulted in specific treatments dictated by the National Collegiate Athletic
      Association(NCAA) and National Federation of State High School Associations
      (NFHS) before an athlete can participate. These guidelines make identification
      and treatment by the athlete's physician imperative. This article provides the
      clinician with specific direction in addressing these dermatologic disorders.

PMID- 15262384
TI  - Infectious mononucleosis: return to play.
AB  - Infectious mononucleosis most commonly affects adolescents and young adults with
      a febrile illness accompanied by pharyngitis,lymph node enlargement, and
      transient fatigue. The diagnosis is usually confirmed with demonstration of
      heterophile antibodies. Typical signs and symptoms are reviewed, along with
      pitfalls in diagnosis and management. The rare complication of splenic rupture
      serves to focus recommendations for returning athletes to strenuous physical
      activities. Because careful prospective studies of infectious mononucleosis in
      athletes are lacking, review of available literature suggests that clinicians may
      recommend a return to all sports in those without spleen enlargement 4 weeks
      after the onset of illness.

PMID- 15262386
TI  - Return to play.

PMID- 15262388
TI  - Ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is the most common nosocomial infection.
      Mortality rates, morbidity, and costs are all increased in the patient with VAP,
      and every measure should thus be taken to prevent its development. There are
      several clearly defined risk factors for VAP, and awareness of these can
      facilitate early diagnosis and hence treatment. In this article, we discuss the
      risk factors, strategies for prevention, approaches to diagnosis and management
      plan for the patient with VAP.

PMID- 15262389
TI  - Developing countries have their own characteristic problems with infection
      control.
AB  - Infection control in developing countries differs markedly from that in the
      developed countries. It is important that both local and international
      authorities take these differences into account when formulating policies for use
      in developing countries. This review examines these issues and sets out some
      suggestions for improvements. The advantages of involving local experts in the
      development of such policies are emphasized.

PMID- 15262390
TI  - Outbreak of nosocomial meningitis caused by Acinetobacter baumannii in
      neurosurgical patients.
AB  - An outbreak of nosocomial meningitis caused by Acinetobacter baumannii, which
      developed postoperatively in seven neurosurgical patients is described. The
      clinical isolates of A. baumannii were typed by biochemical profiles and
      antibiogram patterns, and by random amplified polymorphic DNA polymerase chain
      reaction (RAPD-PCR) and amplified fragment length polymorphism (AFLP)
      fingerprinting. The implicated strain was multi-drug resistant, however,
      susceptibility to imipenem and netilmicin was detected. An extensive search for
      the environmental source of the epidemic strain was carried out. Two of several
      isolates from hospital environment, corresponded to the A. baumannii outbreak
      strain, one being cultured from the suctioning equipment used in the care of
      these patients. The introduction of multiresistant epidemic A. baumannii into a
      neurosurgical unit is a severe risk factor for patients undergoing neurosurgical
      procedures. Genotypic typing methods are important for definitive identification
      of these strains in patients and their environment.

PMID- 15262391
TI  - Metallo-beta-lactamase expressing multi-resistant Acinetobacter baumannii
      transmitted in the operation area.
AB  - Outbreaks of Acinetobacter baumannii demonstrating multiple antibiotic
      resistance, including meropenem resistance, have been described as severe
      therapeutic problems. Here we describe a monoclonal outbreak of infection and
      colonization with multidrug-resistant A. baumannii over a two-month period.
      Resistance to meropenem was mediated by expression of a metallo-beta-lactamase
      enzyme. Four of 14 patients showed clinical signs of infection and two died.
      Contamination of the environment, water, or instruments were excluded as causes
      of the outbreak. All patients, except one, underwent surgery in a specific
      operation theatre where surgery of contamination class IV (infected, dirty) was
      performed. Although individual surgeon error was eliminated, analyses of the
      patients' histories suggested that bacterial transmission had occurred during
      surgery. Five patients showed signs of A. baumannii infection and two of these
      patients suffered from large abdominal wounds infected with a high density of A.
      baumannii requiring repeated revisions. Presumably, these revisions favoured the
      transmission of A. baumannii, which is remarkably resistant to various
      environmental stresses including soaps, disinfectants and dry conditions. No case
      of meropenem-resistant A. baumannii had been observed in the hospital before the
      outbreak. Interestingly, the resistant bacteria appear to have been imported by a
      patient returning from West Africa. This indicates that, similar to MRSA,
      multiresistant A. baumannii may be introduced by patients from foreign hospitals.
      The outbreak was stopped in the following months by reinforcing standard
      procedures and by taking all necessary precautions such as patient isolation, and
      finally only one new case was detected.

PMID- 15262392
TI  - Prevalence of nosocomial infections and use of antibiotics in long-term care
      facilities in Norway, 2002 and 2003.
AB  - There were 42900 institution-beds in long-term care facilities for elderly
      persons in Norway in 2000. This is twice as many as in 1984. Of those living in
      an elderly people's care institution 77% were above 80 years. To determine the
      magnitude and distribution of nosocomial infections in such institutions, the
      Norwegian Institute of Public Health initiated a surveillance system. The system
      is based on two annual one-day prevalence surveys recording the four most common
      nosocomial infections: urinary tract infections, lower respiratory tract
      infections, surgical-site infections and skin infections, as well as antibiotic
      use. All long-term care facilities were invited to participate in the four
      surveys in 2002 and 2003. The total prevalence of the four recorded nosocomial
      infections varied between 6.6 and 7.3% in the four surveys. Nosocomial infections
      occurred most frequently in the urinary tract (50%), followed by infections of
      the skin (25%), of the lower respiratory tract (19%) and of surgical sites (5%).
      The prevalence of nosocomial infections was highest in rehabilitation and short
      term wards, whereas the lowest prevalence was found in special units for persons
      with dementia. In all the surveys the prevalence of the four recorded nosocomial
      infections was higher than the prevalence of patients receiving antibiotics. The
      frequency of nosocomial infections in such facilities highlights the need for
      nosocomial infection surveillance in this population and a need to implement
      infection control measures, such as infection control programmes including
      surveillance of nosocomial infections.

PMID- 15262393
TI  - Risk factors associated with candidaemia in the neonatal intensive care unit: a
      case-control study.
AB  - The incidence of candidaemia is steadily increasing in neonatal intensive care
      units (NICUs). Several neonatal risk factors for candidaemia have been
      identified, however, the number of cases in controlled studies is small and
      knowledge concerning maternal and perinatal risk factors is limited. The present
      study attempted to identify modifiable, independent maternal, perinatal and
      neonatal risk factors for candidaemia using a retrospective case-control study in
      the NICU of a tertiary-care paediatric medical centre. The study group consisted
      of 56 neonates admitted to the NICU between 1996 and 2000 who acquired
      candidaemia. The control group comprised the first infant admitted immediately
      after each study infant matched for gestational age (+/-10 days) and birthweight
      (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared
      between the groups using statistical methods and analysed by univariate and
      multivariate stepwise logistic regression models. The independent risk factors
      found to be significantly associated with increased risk of candidaemia were
      duration of ventilation and presence of bacteraemia before candidaemia. Maternal
      steroids had a significant protective effect. The positive predictive value using
      these three parameters was 78.38%. Maximizing in-utero steroid treatment in high
      risk pregnancies, minimizing the days of mechanical ventilation and investment of
      efforts in prevention of bacteraemia may help to reduce the incidence of
      candidaemia in the NICU.

PMID- 15262394
TI  - Catheter-related bloodstream infection in adult haematology patients: catheter
      removal practice and outcome.
AB  - The aim of the present study was to describe the practice of central venous
      catheter (CVC) removal and outcomes of catheter-related bloodstream infection (CR
      BSI) in adult haematology patients. Patients were identified retrospectively
      according to diagnosis coding of inpatient episodes and evaluated when, on
      examination of medical records, there had been evidence of sepsis with strong
      clinical suspicion that the source was the CVC. Demographic and bacteriological
      data, as well as therapeutic measures and clinical outcomes, were recorded. One
      hundred and three patient episodes were evaluated. The most frequent type of CVC
      was the Hickman catheter and the most frequently isolated pathogen was coagulase
      negative staphylococci. Twenty-five percent of episodes were managed with
      catheter removal. Treatment failure, defined as recurrence of infection within 90
      days or mortality attributed to sepsis within 30 days, occurred significantly
      more frequently in the group managed without catheter removal (52.5% versus 4%, P
      < 0.05). Specifically, 90-day recurrence was more common when the catheter was
      retained (46% versus 0%). However the difference in 30-day attributable mortality
      (7% versus 4%) was not significantly different. Notably, no significant
      difference between the two groups emerged in respect of other measured
      characteristics that had been considered as potential determinants of outcome.
      More frequent CVC removal for CR-BSI, in this population, should be considered.
      Management of CR-BSI without catheter removal is associated with treatment
      failure, morbidity and carries significant resource implications.

PMID- 15262395
TI  - Evolution of closed urinary drainage systems use and associated factors in
      Spanish hospitals.
AB  - Although closed urinary drainage systems (CUDS) reduce the risk of catheter
      associated urinary tract infection (CAUTI), open systems are still used in Spain.
      The object of this work was to describe the progress of CUDS use and factors
      associated with the drainage system type used in Spanish hospitals. The databases
      of the EPINE study (Study of Prevalence of Nosocomial Infections in Spain) from
      1990 to 2000 were used. The EPINE study includes hospitalized patients of all
      ages in acute-care Spanish hospitals. Seventy-six thousand, seven hundred and
      eighty-eight catheterized patients were studied, and the whole database was used
      for the trend analysis of global hospital-acquired infection (HAI). The patient
      and the hospital were the two units of observation used in the analysis. Full
      implementation was defined as 90% CUDS use. A logistic regression model was
      applied to study factors influencing the use of CUDS and to determine prevalence
      trend. An odds ratio (OR) >1 indicates an incremental trend. The Pearson
      correlation coefficient between annual percentage of CUDS use and CAUTI
      prevalence was calculated. Variables for the year 2000 were compared using the
      Mann-Whitney U test between hospitals with and without full implementation. The
      prevalence of urinary catheterized patients in Spain increased from 12.4% in 1990
      to 15.2% in 2000 (OR 1.019, 95% CI 1.016-1.021). The proportion of CUDS used
      increased from 50.6% in 1990 to 70% in 2000 (OR 1.1, 95% CI 1.095-1.104) and
      correlated with a significant decrease of UTIs (r = 0.65, P = 0.03). In 1990,
      28.5% of hospitals had full implementation of CUDS and by 2000 this had risen to
      40.3% (OR 1.093, 95% CI 1.06-1.127). Patients in medium (200-500 beds) and large
      (>500 beds) hospitals, as well as those with three of more diagnoses and two or
      more intrinsic risk factors had an increased probability of having a CUDS,
      whereas being hospitalized in areas other than intensive care, being male and
      less than 65 years old were associated with a lower probability of CUDS use. The
      median prevalence of catheterized patients in hospitals with full implementation,
      was significantly lower than in those without it (P = 0.049). Although CUDS use
      is increasing, there is still much work required to reach full implementation.
      Keeping CUDS for more severely ill patients may reflect a higher concern over the
      consequences of UTI in these patients. Nevertheless, it is necessary to change a
      practice that exposes patients to a known UTI risk factor and reach a consensus
      on indications for catheter insertion.

PMID- 15262396
TI  - Tuberculosis among healthcare workers in a tertiary-care hospital in South India.
AB  - It is possible that tuberculosis is transmitted from patients to healthcare
      workers (HCWs). However, there are few data on this from developing countries.
      The object of this study was to document the incidence of tuberculosis among HCWs
      in the Christian Medical College (CMC), Vellore, India during a 10-year period
      (January 1992-December 2001). Data were collected from records maintained in the
      staff and students health services of CMC. A total of 125 cases were diagnosed
      during the period of study. The overall incidence of sputum positive cases was
      similar to that observed in the general population, during most years. However,
      it appears that focal outbreaks occur with transmission between HCWs. The chance
      of developing extra-pulmonary tuberculosis was higher in HCWs compared with the
      general population.

PMID- 15262397
TI  - A practical lesson in negative-pressure isolation ventilation.

PMID- 15262398
TI  - High-level disinfection of cystoscopic equipment with ortho-phthalaldehyde
      solution.

PMID- 15262399
TI  - Useful oldies: oral antibiotics for the treatment of MRSA infections.

PMID- 15262400
TI  - Louis Pasteur and cigarettes.

PMID- 15262401
TI  - Eye colour: portals into pigmentation genes and ancestry.
AB  - Several recent papers have tried to address the genetic determination of eye
      colour via microsatellite linkage, testing of pigmentation candidate gene
      polymorphisms and the genome wide analysis of SNP markers that are informative
      for ancestry. These studies show that the OCA2 gene on chromosome 15 is the major
      determinant of brown and/or blue eye colour but also indicate that other loci
      will be involved in the broad range of hues seen in this trait in Europeans.

PMID- 15262402
TI  - Unexpected conserved non-coding DNA blocks in mammals.
AB  - The significance of non-coding DNA is a longstanding riddle in the study of
      molecular evolution. Using a comparative genomics approach, Dermitzakis and
      colleagues have recently shown that at least some non-coding sequence, frequently
      ignored as meaningless noise, might bear the signature of natural selection. If
      functional, it could mark a turning point in the way we think about the evolution
      of the genome.

PMID- 15262403
TI  - Antibody class switching: uncoupling S region accessibility from transcription.
AB  - Immunogloblin class switch recombination (CSR) is a regulated process that
      changes antibody effector functions. Recently, Nambu et al. showed that histone
      acetylation is induced at switch (S) regions undergoing CSR; however, histone
      acetylation without accompanying S region transcription is insufficient to
      attract activation-induced cytidine deaminase (AID), which is required for CSR.
      They also show that AID can associate with RNA polymerase II. These results
      support the model that germline transcripts are required to form single-stranded
      DNA, the AID substrate and further suggest that AID is recruited to S regions by
      the transcriptional machinery.

PMID- 15262404
TI  - Comparative genomics for reliable protein-function prediction from genomic data.
AB  - Genomic data provide invaluable, yet unreliable information about protein
      function. However, if the overlap in information among various genomic datasets
      is taken into account, one observes an increase in the reliability of the protein
      function predictions that can be made. Recently published approaches achieved
      this either by comparing the same type of data from multiple species (horizontal
      comparative genomics) or by using subtle, Bayesian methods to compare different
      types of genomic data from a single species (vertical comparative genomics). In
      this article, we discuss these methods, illustrating horizontal comparative
      genomics by comparing yeast two-hybrid (Y2H) data from Saccharomyces cerevisiae
      with Y2H data from Drosophila melanogaster, and illustrating vertical comparative
      genomics by comparing RNA expression data with proteomic data from Plasmodium
      falciparum.

PMID- 15262405
TI  - Of statistics and genomes.
AB  - Higher organisms have more genes and larger genomes than simple organisms. This
      statement sounds almost too trivial to ask the question: why? But there are at
      least two different answers. Either there is an inherent necessity to increase
      genome size when more complexity is required or genome size increases because of
      other reasons that then enable complexity to "latch on". Recently, an article by
      Lynch and Conery, which used arguments of evolutionary population dynamics,
      proposed that low population size leads to larger genomes. This then provides the
      opportunity to generate more complex organisms.

PMID- 15262406
TI  - Recombination, GC-content and the human pseudoautosomal boundary paradox.
AB  - The pseudoautosomal boundary of mammalian sex chromosomes separates a low
      recombination region (X- or Y-specific) from a high-recombination region (the
      pseudoautosomal region), providing a good opportunity to investigate the
      influence of recombination on molecular evolutionary processes. The mouse and
      human patterns of sequence variation, however, are discordant: a striking
      difference of GC-content and evolutionary rate was reported between the proximal
      and distal sides of the pseudoautosomal boundary in the mouse genome, whereas
      this difference was not found in the human genome. The paradox might be explained
      by the mirror histories of the pseudoautosomal boundary in the two species, and
      by the asymmetric nature of the forces driving GC-content evolution in mammalian
      genomes.

PMID- 15262407
TI  - An integrated epigenetic and genetic approach to common human disease.
AB  - Epigenetic information is heritable during cell division but is not contained
      within the DNA sequence itself. Despite increasing evidence for and interest in
      the role of epigenetics in human disease, particularly in cancer, virtually no
      epigenetic information is routinely or systematically measured at the genome
      level. The current population-based approach to common disease relates common DNA
      sequence variants to either disease status or incremental quantitative traits
      contributing to disease. Although this purely genetic approach is powerful and
      general, there is currently no conceptual framework to integrate epigenetic
      information. In this article, we propose an approach to common human disease that
      incorporates epigenetic variation into genetic studies. Epigenetic variation
      might also help to explain the late onset and progressive nature of most common
      diseases, the quantitative nature of complex traits and the role of environment
      in disease development, which a purely sequence-based approach might not.

PMID- 15262408
TI  - Piecing together evolution of the vertebrate endocrine system.
AB  - One of the great challenges in biology is to understand how particular complex
      morphological and physiological characters originated in specific evolutionary
      lineages. In this article, we address the origin of the vertebrate hypothalamic
      pituitary-peripheral gland (H-P-PG) endocrine system, a complex network of
      specialized tissues, ligands and receptors. Analysis of metazoan nucleotide and
      protein sequences reveals a patchwork pattern of H-P-PG gene conservation between
      vertebrates and closely related invertebrates (ascidians). This is consistent
      with a model of how the vertebrate H-P-PG endocrine system could have emerged in
      relatively few steps by gene family expansion and by regulatory and structural
      modifications to genes that are present in a chordate ancestor. Some of these
      changes might have resulted in new connections between metabolic or signaling
      pathways, such as the bridging of 'synthesis islands' to form an efficient system
      for steroid hormone synthesis.

PMID- 15262409
TI  - The different roles of tryptophan transfer RNA in regulating trp operon
      expression in E. coli versus B. subtilis.
AB  - Escherichia coli and Bacillus subtilis use different mechanisms of sensing and
      responding to tryptophan and uncharged tRNA(Trp) as regulatory signals. In E.
      coli, tryptophan activates a repressor that binds to the trp promoter- operator,
      inhibiting transcription initiation. In B. subtilis, tryptophan activates an RNA
      binding protein, TRAP, which binds to the trp operon leader RNA, causing
      transcription termination. In E. coli uncharged tRNA(Trp) accumulation stalls the
      ribosome attempting translation of tandem Trp codons in the leader-peptide coding
      region of the operon. This stalling permits the formation of an RNA
      antiterminator structure, preventing transcription termination. In B. subtilis
      uncharged tRNA(Trp) accumulation activates transcription and translation of the
      at operon. AT protein inhibits tryptophan-activated TRAP, thereby preventing TRAP
      mediated transcription termination. These differences might reflect the unique
      organizational features of the respective trp operons and their ancestry.

PMID- 15262410
TI  - Agrobacterium T-DNA integration: molecules and models.
AB  - Genetic transformation mediated by Agrobacterium involves the transfer of a DNA
      molecule (T-DNA) from the bacterium to the eukaryotic host cell, and its
      integration into the host genome. Whereas extensive work has revealed the
      biological mechanisms governing the production, Agrobacterium-to-plant cell
      transport and nuclear import of the Agrobacterium T-DNA, the integration step
      remains largely unexplored, although several different T-DNA integration
      mechanisms have been suggested. Recent genetic and functional studies have
      revealed the importance of host proteins involved in DNA repair and maintenance
      for T-DNA integration. In this article, we review our understanding of the
      specific function of these proteins and propose a detailed model for integration.

PMID- 15262411
TI  - Gene expression systems in Drosophila: a synthesis of time and space.
AB  - Until recently, ectopic gene expression in Drosophila was largely accomplished
      through the use of the heat-shock promoter, which provides the experimenter with
      temporal control over transgene induction, or the GAL4-UAS system, which provides
      the experimenter with spatial control over transgene expression. But significant
      advances have now been made in combining the attributes of temporal and spatial
      control over gene expression into a single system. In this article, we review the
      progress on the development and implementation of several gene expression systems
      that offer control in time and space. These include systems employing the yeast
      FLP recombinase gene and FRT sites (FLP and/or FRT), tetracycline-responsive
      transcription factors (Tet-On and Tet-Off), steroid hormone responsive
      transcription factors (GeneSwitch and ER-GAL4) and temperature-sensitive
      repressors of the classical GAL4-UAS system (TARGET).

PMID- 15262412
TI  - Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid
      tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT).
AB  - The successful treatment of cancer by boron neutron-capture therapy (BNCT)
      requires the selective delivery of relatively high concentration of 10B compounds
      to malignant tumor tissue. This study focuses on a new tumor-targeting drug
      delivery system for BNCT that uses small (less than 200 nm in diameter),
      unilamellar mercaptoundecahydrododecaborate (BSH)-encapsulating, transferrin (TF)
      conjugated polyethyleneglycol liposomes (TF-PEG liposomes). When TF-PEG liposomes
      were injected at a dose of 35 mg 10B/kg, we observed a prolonged residence time
      in the circulation and low uptake by the reticuloendothelial system (RES) in
      Colon 26 tumor-bearing mice, resulting in enhanced accumulation of 10B into the
      solid tumor tissue (e.g., 35.5 microg/g). TF-PEG liposomes maintained a high 10B
      level in the tumor, with concentrations over 30 microg/g for at least 72 h after
      injection. This high retention of 10B in tumor tissue indicates that binding and
      concomitant cellular uptake of the extravasated TF-PEG liposomes occurs by TF
      receptor and receptor-mediated endocytosis, respectively. On the other hand, the
      plasma level of 10B decreased, resulting in a tumor/plasma ratio of 6.0 at 72 h
      after injection. Therefore, 72 h after injection of TF-PEG liposomes was selected
      as the time point of BNCT treatment. Administration of BSH encapsulated in TF-PEG
      liposomes at a dose of 5 or 20 mg 10B/kg and irradiation with 2 x 10(12)
      neutrons/cm2 for 37 min produced tumor growth suppression and improved long-term
      survival compared with PEG liposomes, bare liposomes and free BSH. Thus,
      intravenous injection of TF-PEG liposomes can increase the tumor retention of 10B
      atoms, which were introduced by receptor-mediated endocytosis of liposomes after
      binding, causing tumor growth suppression in vivo upon thermal neutron
      irradiation. These results suggest that BSH-encapsulating TF-PEG liposomes may be
      useful as a new intracellular targeting carrier in BNCT therapy for cancer.

PMID- 15262413
TI  - PLGA/mesoporous silica hybrid structure for controlled drug release.
AB  - In this paper, we report a poly(D,L-lactide-co-glycolide) (PLGA)/mesoporous
      silica hybrid structure (PS hybrid structure), which was synthesized via a novel
      sol-gel route assisted by single emulsion solvent evaporation. The in intro drug
      release properties of both the mesoporous silica and the PS hybrid structure were
      investigated. It was observed that gentamicin-loaded mesoporous silica showed a
      sharp initial burst during the first day followed by a rather constant and low
      release over the subsequent period of 3 weeks. In comparison with the mesoporous
      silica without biodegradable polymer encapsulation, the PS hybrid structure could
      realize a reduced initial burst, with a plateau stage for nearly 3 weeks of slow
      release, followed by a sustained release stage lasting for nearly 2 weeks. The
      whole release period could last as long as 5 weeks. These distinct behaviors make
      the hybrid structure material promising as a new drug release material for bone
      filling applications.

PMID- 15262414
TI  - A novel pH-dependent gradient-release delivery system for nitrendipine: I.
      Manufacturing, evaluation in vitro and bioavailability in healthy dogs.
AB  - A novel pH-dependent gradient-release delivery system was developed by mixing
      three kinds of pH-dependent microspheres. Nitrendipine, a dihydropyridine calcium
      antagonist, was selected as the poorly water-soluble model drug. To obtain
      gradient-release of the active drug in the stomach, duodenum and lower segment of
      the small intestine, respectively, three kinds of pH-dependent polymers, i.e.
      Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose phthalate and
      Hydroxypropylmethylcellulose acetate succinate, were formulated to produce the
      microspheres, which dissolve at an acid condition, the pH of > or = 5.5 and > or
      = 6.5, respectively. The quasi-emulsion solvent diffusion method was employed in
      the manufacturing process for the microspheres. All three kinds of microspheres
      had a highly spherical shape and high incorporation efficiency (>91.0%). The
      particle sizes were mainly affected by the agitation speed and temperature of the
      manufacturing process. The results of X-ray diffraction suggested that
      nitrendipine in the microspheres was molecularly dispersed in an amorphous state.
      The drug dissolution behavior of the system under the simulated gastrointestinal
      pH conditions revealed obvious gradient-release characteristics. The dissolution
      profiles and content of the systems stored at a temperature of 40 degrees C and a
      relative humidity of 75% were unchanged during a 3-month period of accelerating
      storage conditions. The results of the bioavailability testing in six healthy
      dogs suggested that the pH-dependent gradient-release delivery system could
      improve efficiently the uptake of the poorly water-soluble drug and prolong the
      Tmax value in vivo.

PMID- 15262415
TI  - Transport of PLA-PEG particles across the nasal mucosa: effect of particle size
      and PEG coating density.
AB  - The aim of the study was to investigate the effect of the size and PEG coating
      density of Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nano- and
      microparticles on their transport across the nasal mucosa. Particles were made of
      PLA-PEG copolymers of two different molecular weights (Mw: 37 and 28 kDa) and
      also PLA of Mw 28 kDa, and prepared using different techniques (simple emulsion
      (o/w), double emulsion (w/o/w), and nanoprecipitation techniques). The particles
      were characterized for their size, zeta potential, morphology [Transmission
      Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)], and PEG
      coating efficiency. Additionally, the transport of rhodamine 6G-labelled PLA-PEG
      and PLA particles across the rat nasal mucosa was investigated by Confocal Laser
      Scanning Microscopy (CLSM). The results showed that the size of PLA-PEG
      nanoparticles varied between 150 and 300 nm and their zeta potential between -10
      and -22 mV depending on both the polymer Mw and the preparation technique.
      Moreover, the PEG coating efficiency (amount of PEG on the surface with respect
      to the total amount of PEG in the particles) was high (between 75% and 92%) and
      affected by the PLA Mw and also by the particles preparation technique. The
      greatest PEG surface density was achieved for lowest Mw PLA-PEG, using the O/W
      emulsification technique. The CLSM images of nasal epithelia from rats showed the
      importance of the PEG coating density and the size on the transmucosal transport
      of the fluorescent nanoparticles. More specifically, PLA-PEG particles with a
      high PEG coating density and a small size were more significantly transported
      than noncoated PLA nanoparticles and also than PLA-PEG nanoparticles with a lower
      coating density. In conclusion, these results showed the important role that the
      PEG coating has on the efficacy of PLA-PEG nanoparticles as nasal drug carriers.

PMID- 15262416
TI  - Fabrication of porous hollow silica nanoparticles and their applications in drug
      release control.
AB  - Preparation and characterization of porous hollow silica nanoparticles (PHSN) for
      controlled release applications were investigated. Through orthogonally designed
      experiments, the optimal synthesis conditions for the preparation of PHSN were
      obtained and the produced PHSN were characterized by BET, SEM, TEM and IR.
      Scanning and transmission electron microscopy images revealed their hollow shell
      core structure and also demonstrated that the size and shape of PHSN are
      determined by the templating CaCO3 nanoparticles. The produced PHSN were applied
      as a carrier to study the controlled release behaviors of Brilliant Blue F (BB),
      which was used as a model drug. Being loaded into the inner core and on the
      surfaces of the nanoparticles, BB was released slowly into a bulk solution for
      about 1140 min as compared to only 10 min for the normal SiO2 nanoparticles, thus
      exhibited a typical sustained release pattern without any burst effect. In
      addition, higher BET of the carriers, lower pH value and lower temperature
      prolonged BB release from PHSN, while stirring speed showed little influence on
      the release behavior. It showed that PHSN have a promising future in controlled
      drug delivery applications.

PMID- 15262417
TI  - Imparting bone mineral affinity to osteogenic proteins through heparin
      bisphosphonate conjugates.
AB  - Although numerous growth factors can promote the regeneration of bone upon
      parenteral administration, all exhibit undesirable side-effects that prevent
      their clinical utility. These side-effects arise due to the growth factors'
      inherent lack of bone affinity. The goal of this study was to develop a means to
      enhance the bone mineral affinity of osteogenic growth factors so as to minimize
      their extra-skeletal distribution. Heparin, a glycosaminoglycan that exhibits a
      high affinity to numerous growth factors, was modified with bisphosphonates to
      enhance its affinity to bone mineral (i.e. hydroxyapatite, HA). To this end,
      conjugation of 1-amino-1,1-diphosphonate methane (aminoBP) onto periodate
      oxidized heparin using 4-(maleimidomethyl)cyclohexane-1-carboxyl-hydrazide was
      attempted. Using this chemistry, the number of aminoBPs conjugated onto heparin
      was modulated by varying the reacting reagent concentrations (to a maximum of 7
      aminoBPs per heparin). Increasing the number of aminoBPs resulted in a more than
      twofold increase in heparin's affinity for HA in vitro. Subsequently, the ability
      of aminoBP-heparin conjugates to enhance the mineral affinity of basic fibroblast
      growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) was explored. The
      results revealed that the complexation between the conjugates and growth factors
      had occurred and that the conjugates increased the bone mineral affinity of bFGF
      and BMP-2 in an aminoBP-dependent manner. In conclusion, the conjugation of
      aminoBP onto heparin is a feasible approach to enhance the affinity of heparin
      binding, osteogenic growth factors to HA.

PMID- 15262419
TI  - Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury.
AB  - The goal of this work was to assess the feasibility of using affinity-based
      delivery systems to release neurotrophin-3 (NT-3) in a controlled manner from
      fibrin gels as a therapy for spinal cord injury. A heparin-based delivery system
      (HBDS) was used to immobilize NT-3 within fibrin gels via non-covalent
      interactions to slow diffusion-based release of NT-3, thus allowing cell
      activated degradation of fibrin to mediate release. The HBDS consists of three
      components: immobilized linker peptide, heparin and NT-3. The linker peptide
      contained a Factor XIIIa substrate and was covalently cross-linked to fibrin
      during polymerization. This immobilized linker peptide sequesters heparin within
      fibrin gels, and sequestered heparin binds NT-3, preventing its diffusion.
      Mathematical modeling was performed to examine the effect of heparin
      concentration on the fraction of NT-3 initially bound to fibrin. In vitro release
      studies confirmed that heparin concentration modulates diffusion-based release of
      NT-3. Fibrin gels containing the HBDS and NT-3 stimulated neural outgrowth from
      chick dorsal root ganglia by up to 54% versus unmodified fibrin, demonstrating
      that the NT-3 released is biologically active. In a preliminary in vivo study,
      fibrin gels containing the HBDS and NT-3 showed increased neural fiber density in
      spinal cord lesions versus unmodified fibrin at 9 days.

PMID- 15262420
TI  - Combined approach of FTIR imaging and conventional dissolution tests applied to
      drug release.
AB  - A new method is developed to study drug release using a combination of FTIR
      imaging and conventional dissolution tests. FTIR imaging in attenuated total
      reflection (ATR) mode allows simultaneous measurements of the distribution of
      different components in the tablet, e.g., drug, polymer and water as a function
      of time. These imaging measurements were carried out in a combined compaction and
      flow-through cell, which was linked to a UV detector to quantify the amount of
      dissolved drug. In this way, changes in drug concentration in the aqueous
      solution can be studied similarly to the conventional dissolution test. This
      combination provides quantitative information of changes in both the tablet and
      the liquid phase. A tablet composed of hydroxypropyl methylcellulose (HPMC) and
      niacinamide was prepared and analysed using this setup. Mathematical processing
      of the measured spectra with a partial least squares (PLS) calibration was
      utilised for accurate quantitative analysis of the concentrations of different
      components. The results of FTIR imaging and the dissolution test are compared.

PMID- 15262418
TI  - Chitosan delivery systems for the treatment of oral mucositis: in vitro and in
      vivo studies.
AB  - Oral mucositis is a frequent and potentially severe complication of radiation or
      chemotherapy for cancer. Associated with atrophy and ulceration of the oral
      mucosa is an increased risk of infection, and the most common pathogenic agent is
      Candida. Chitosan is an excellent candidate for the treatment of oral mucositis.
      Its bioadhesive and antimicrobial properties offer the palliative effects of an
      occlusive dressing and the potential for delivering drugs, including anti
      candidal agents. The aim of this study was to develop an occlusive bioadhesive
      system for prophylaxis and/or treatment of oral mucositis. Gel and film
      formulations were prepared using chitosans at different molecular weights and in
      different solvents. Nystatin, which is considered as a prophylactic agent for
      oral mucositis was incorporated into the formulations. The in vitro release of
      nystatin from the formulations was decreased with the increasing molecular weight
      of chitosan. The effect of the formulations was investigated in vivo in hamsters
      with chemotherapy-induced mucositis. Mucositis scores in groups treated with
      nystatin incorporated into gel and suspension formulations were significantly
      lower (p < 0.05) than those treated with the chitosan gel alone. Survival of
      animals in the treated groups was higher than that in the control group. The
      retention time and distribution of the gels in the oral cavity were investigated
      in healthy volunteers. A faster distribution of nystatin in the oral cavity was
      obtained using the suspension compared to the gels, but the nystatin saliva level
      decreased rapidly as well. A drug concentration above the minimum inhibitory
      concentration (MIC) value for Candida albicans (0.14 microg/ml) was maintained
      for longer periods of time at the application site (90 min) than at the
      contralateral site (45 min) in the oral cavity.

PMID- 15262423
TI  - Cytosolic soluble proteins induce DNA release from DNA--gene carrier complexes.
AB  - In nonviral transfection systems, the gene carrier/DNA complex must undergo
      several steps for successful transgene expression. DNA release from the complex
      is one important step. However, the detailed mechanism of intracellular processes
      involved in DNA release is not well understood. In this study, to clarify the
      dissociation of the complex in the cytosol, we investigated whether the DNA
      release was caused by addition of a cytosolic fraction prepared from mouse liver
      to the complex. When Lipofectamine (a liposome-type gene carrier) was used as a
      complex forming reagent with DNA, the cytosolic fraction caused no DNA release
      from the complex. In contrast, when dendritic poly(L-lysine) and jetPEI (polymer
      type gene carriers) were used, DNA release was observed when the complex formed
      at a low cation/anion ratio. This result showed that a DNA releasing factor was
      present in the cytosolic fraction, suggesting that in the cytosol the DNA was
      spontaneously released from a gene carrier/DNA complex when the carrier was a
      polymer-type gene carrier. Furthermore, this DNA releasing ability of the
      cytosolic fraction was protease sensitive.

PMID- 15262421
TI  - Surfactant-enhanced transdermal delivery by electroporation.
AB  - The objective of the experiment was to study the influence of sodium dodecyl
      sulfate (SDS) on transdermal transport of diffusants by electroporation. The
      resistance of porcine epidermis in contact with SDS solution (0.2% w/v) dropped
      by 40% within 24 h. SDS improved the efficiency of transdermal delivery of
      glucose, dextrans of molecular weight (MW) 4 kDa (FD4K) and 10 kDa (FD10K) by
      electroporation. However, the transport of dextran MW 35 kDa (FD35K) was not
      influenced significantly. Pretreatment of epidermis with SDS solution reduced its
      electroporation threshold from 80 to 60 V. It appears that presence of SDS during
      electroporation helps in achieving the desired transport with less electrical
      exposure dose. SDS enhanced the transdermal delivery of molecules by
      electroporation most likely by facilitating the barrier disruption during pulse
      application and also by prolonging the lifetime of electropores created by the
      pulse.

PMID- 15262422
TI  - Development of a non-viral multifunctional envelope-type nano device by a novel
      lipid film hydration method.
AB  - The development of a multifunctional envelope-type nano device (MEND) for use in
      a non-viral gene delivery system using a novel lipid film hydration method is
      described. This packaging method involves three steps: (i) DNA condensation with
      a polycation, (ii) lipid film hydration for the electrostatic binding of the
      condensed DNA, and (iii) sonication to package the condensed DNA with lipids. For
      DNA condensation, the optimum ratio of DNA to poly-L-lysine (PLL) was determined
      by titrating DNA and PLL. The condensed DNA/PLL complex (DPC) was coated with a
      lipid bilayer by lipid film hydration followed by sonication, which was confirmed
      by sucrose density gradient centrifugation. Packaging of DPC with lipids
      increased the transfection activity 10-fold over that of DPC. MEND, having
      octaarginine on the envelope as a device for membrane penetration to enhance
      cellular uptake, showed a 1000-fold higher transfection activity than DPC. The
      MEND developed in this study represents a promising non-viral gene delivery
      system.

PMID- 15262424
TI  - Expression of fibronectin and HIF-1alpha in renal cell carcinomas: relationship
      to von Hippel-Lindau gene inactivation.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene (TSG) at 3p25 is mutated in
      approximately 50% of conventional (clear cell) renal cell carcinomas (cRCC). VHL
      normally regulates the ubiquitin-mediated proteolysis of hypoxia-inducible factor
      1alpha (HIF-1alpha), and VHL inactivation results in increased cellular HIF
      1alpha expression. VHL protein (pVHL) also interacts with fibronectin (Fn) and
      VHL inactivation results in defective Fn extracellular matrix assembly. The
      present study investigated the immunohistochemical (IHC) staining for Fn and HIF
      1alpha in 11 cRCC and the relationship of the staining to VHL inactivation by
      gene deletion, mutation, or hypermethylation. Evidence for VHL inactivation by 3p
      deletions and VHL mutations were found in six tumors. Fn-positive IHC staining of
      tumor cells and negative to weak staining of extracellular stroma was found in
      five cases having exon 1 or exon 2 mutations. In contrast, Fn staining was absent
      in tumor cells and positive in the stroma of five tumors without VHL inactivation
      and in one tumor with a C-terminal exon 3 mutation. HIF-1alpha tumor cell
      staining was present in the cRCC with VHL inactivation but was also present in
      two tumors having 3p deletions but neither mutation nor hypermethylation of VHL.
      These two cRCC showed a tumor cell-negative and stroma-positive pattern of Fn
      staining. The findings indicate that VHL inactivation plays a role in the
      development of some cRCC by altering Fn cell--stroma relationships. They also
      suggest that some C-terminal mutations may not interfere with Fn assembly and
      that a 3p TSG in addition to VHL influences HIF-1alpha degradation.

PMID- 15262425
TI  - WRN gene and other genetic factors affecting immortalization of human B
      lymphoblastoid cell lines transformed by Epstein-Barr virus.
AB  - The immortalization of human B-lymphoblastoid cell lines (LCL) transformed by
      Epstein-Barr virus (EBV) is accompanied by two major events: increase in
      telomerase activity and change in karyotype from normal diploid to aneuploidy. We
      investigated the effect of genetic factors on the incidence of immortalization by
      putting old and new data together to collect enough samples for statistical
      analysis. Among 50 LCL from normal individuals, 5 LCL (10.0%) were immortalized
      and the remaining 45 LCL were mortal. None of the 44 LCL (0%; P < 0.031 against
      normal individuals by chi square test) from patients having Werner syndrome (WS),
      a recessive genetic disorder showing premature aging, were immortalized. Among 11
      LCL from a family with a tendency to have hereditary type 2 diabetes mellitus, 5
      LCL (45.5%; P < 0.0040 against normal individuals, P < 0.00001 against WS
      patients) were immortalized. Duplicated measurements of the lifespan of 33 LCL
      showed a good coincidence (r=0.785) between the first and second estimations,
      indicating that each mortal LCL has a predetermined lifespan. These results
      strongly suggest that the normal WRN gene, the causative gene of WS, is essential
      for LCL to immortalize, and genetic factor(s) of a family having diabetes
      mellitus increases immortalization, implicating that host genetic factors affect
      immortalization of EBV and probably carcinogenesis by EBV.

PMID- 15262426
TI  - Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas
      without detectable NR4A3 fusion genes.
AB  - Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal tumor
      cytogenetically characterized by reciprocal translocations, such as
      t(9;22)(q22;q12) and t(9;17)(q22;q11), which result in EWSR1/NR4A3 and
      TAF15/NR4A3 fusion genes (alias EWS/NOR1, TAF2N/NOR1), respectively. NOR1 is an
      orphan nuclear receptor and acts as a transcription factor that can bind to its
      putative coactivator, SIX3. Although the NOR1 fusion protein has been implicated
      in oncogenesis of EMC, a small fraction of EMC lacks detectable rearrangements of
      the NR4A3 gene or 9q22. We report a case of EMC with no detectable NR4A3 gene
      alterations, as assessed with various molecular techniques including reverse
      transcription-polymerase chain reaction (RT-PCR), Southern blotting, interphase
      fluorescence in situ hybridization, and PCR single-strand conformation
      polymorphism-but with coexpression of native NOR1 and SIX3. In our survey of
      another 18 EMCs, we identified one more case expressing both NOR1 and SIX3 but
      lacking NR4A3 fusion. Fourteen tumors with detectable NR4A3 fusion genes (EWSR1
      NR4A3; TAF15-NR4A3) expressed neither native NOR1 nor SIX3. SIX3 expression is
      normally confined specifically to the developing eye and fetal forebrain,
      although the expression of NR4A3 is largely ubiquitous. Our data suggest that
      aberrant coexpression of NOR1 and SIX3 is a potential alternative mechanism
      underlying the development of EMC.

PMID- 15262427
TI  - MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements
      and 11q proximal breakpoint heterogeneity.
AB  - Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10
      (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We
      present two new pediatric cases (French-American-British type M5) with MLL-MLLT10
      fusion, which we studied with fluorescence in situ hybridization. In both we
      detected a paracentric inversion of the 11q region that translocated onto
      chromosome 10p12; one case displayed a variant complex pattern. We review the
      cytogenetic molecular data concerning the proximal inversion breakpoint of 11q
      and confirm its heterogeneity.

PMID- 15262428
TI  - Characterization of PMP22 expression in osteosarcoma.
AB  - The peripheral myelin protein (PMP22) gene is highly expressed in peripheral
      Schwann cells and encodes an important constituent of the myelin sheath. It is
      also expressed at lower levels in other normal tissues in which the protein is
      supposed to be involved in cell growth regulation. We recently reported frequent
      amplification and overexpression of PMP22 in high-grade osteosarcoma. Here, we
      analyzed PMP22 expression in five osteosarcoma tumors and three osteosarcoma cell
      lines. In normal Schwann cells, transcription of PMP22 starts at three promoters,
      P1A, P1B, and P2, which results in the synthesis of three alternatively spliced
      transcripts that all code for the same protein. We found a comparable expression
      pattern in normal osteoblasts. However, promoter P1A-driven transcripts were
      absent in all investigated tumors and cell lines and, compared to normal
      osteoblasts, the P1B/P2 transcript ratio was found to be increased in two of
      three cases with PMP22 overexpression and decreased in all five cases without
      overexpression. In normal Schwann cells and in NIH3T3 cells, PMP22 expression
      increases upon serum starvation-induced growth arrest. In contrast to this, serum
      withdrawal caused a considerable decrease of PMP22 expression in the osteosarcoma
      cell lines. We conclude that the different PMP22 expression in osteosarcoma may
      result in alternative availability of the PMP22 protein during the cell cycle and
      aberrant regulation of cell growth control in osteosarcoma tumorigenesis.

PMID- 15262429
TI  - DNA sequence copy number aberrations in prostate cancers: a comparison of
      comparative genomic hybridization data between Japan and European countries.
AB  - Incidence of prostate cancer in Japan and resultant mortality rates are lower
      than in Western countries. To elucidate the reasons behind this, the genetic
      characteristics of prostate cancer in Japanese patients were investigated.
      Comparative genomic hybridization was applied in 27 cases of prostate cancers in
      Japanese patients. Frequent gains were found at Xq, 8q, Xp, and 7q and frequent
      losses at 8p, 6q, 2q, 16q, and 17p (in decreasing order of frequency). Loss of 6q
      was frequently detected in both early and advanced tumors. Gains of 7q and 8q and
      loss of 8p were more frequent in advanced than early tumors. The frequency of 13q
      loss in primary tumors was significantly lower in patients in Japan than in
      European countries. These data suggest that a loss of 6q is associated with the
      development of prostate cancer, and that gains of 7q and 8q and a loss of 8p are
      linked with cancer progression. The frequency of 13q loss may imply differences
      in biological behavior of prostate cancer between Japan and Western countries.

PMID- 15262430
TI  - Amplification of MGC2177, PLAG1, PSMC6P, and LYN in a malignant mixed tumor of
      salivary gland detected by cDNA microarray with tyramide signal amplification.
AB  - Gene amplifications have been observed in many different tumor cells, and many of
      these changes are related to tumor pathogenesis. Comparative genomic
      hybridization (CGH) using metaphase chromosomes can detect changes in chromosome
      copy number with a resolution of 10-20 Mb. Current advances in CGH analysis in a
      microarray format allow us to refine such changes down to the gene level. We
      applied microarray technology to detect novel gene amplification in a malignant
      mixed tumor of salivary gland. Besides detecting previously known gene
      amplifications (MDM2 and MYC), we identified four other highly amplified genes
      located at 8q11.2 approximately q13: MGC2177, PLAG1, PSMC6P, and LYN. The
      amplification was further validated with real-time quantitative polymerase chain
      reaction.

PMID- 15262431
TI  - Dicentric (19;21)(p13;p13), a novel chromosomal abnormality occurring in a case
      of Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - We report on a patient with Philadelphia chromosome-positive acute lymphoblastic
      leukemia, who acquired a novel chromosomal abnormality, a dic(19;21)(p13;p13),
      during relapse of the disease. The cytogenetic result was confirmed by
      fluorescence in situ hybridization using alpha-satellite and library probes
      specific for chromosomes 19 and 21, respectively, as well as a chromosome 19q13.1
      specific DNA probe. In our case, the dic(19;21) represents a secondary genetic
      change and was associated with disease progression and poor prognosis.

PMID- 15262432
TI  - Secondary Philadelphia chromosome in a patient with acute lymphoblastic leukemia.
AB  - We report the case of a patient with acute lymphoblastic leukemia who developed a
      secondary Philadelphia chromosome-positive clone (Ph(+)). Although the Ph was not
      detected at diagnosis with conventional cytogenetic analysis and with molecular
      methods (reverse transcriptase polymerase chain reaction), the Ph was detected
      with the same techniques at relapse. This anomaly is usually related to the
      initiation of the disease, but can be a late event related to progression. We
      discuss these hypotheses and review the literature.

PMID- 15262433
TI  - Sclerosing epithelioid fibrosarcoma with der(10)t(10;17)(p11;q11).
AB  - Sclerosing epithelioid fibrosarcoma is a recently described, rare mesenchymal
      neoplasm. We report a case of sclerosing epithelioid fibrosarcoma that occurred
      in the lower leg of a 48-year-old man. The karyotype of the tumor exhibited
      der(1)t(1;10)(p31;p11), der(10)t(10;17)(p11;q11), and der(17) t(11;17)(?;q11).
      Rearrangement of 10p11 was also found in one previous reported case of this
      uncommon tumor.

PMID- 15262434
TI  - IGH gene involvement in two cases of acute lymphoblastic leukemia with
      t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ
      hybridization.
AB  - Translocation (14;14)(q11;q32) or inv(14)(q11q32) is a common cytogenetic
      aberration in T-cell leukemia associated with ataxia-telangiectasia (AT);
      however, rare reports have indicated that this abnormality also occurs in B
      lineage acute lymphoblastic leukemia (ALL). We report here two cases with common
      type ALL exhibiting the chromosomal aberration t(14;14)(q11;q32). The
      immunophenotype showed the blasts were positive for CD9, CD10, CD38, CD22, and
      CD15 in case 1 and positive for CD2, CD9, CD10, CD19, CD38, CD20, and CD22 in
      case 2, but negative for CD3, CD4, and CD8 expression in both cases. The
      cytogenetic analysis revealed del(6)(q22), and t(14;14)(q11;q32) in case 1 and
      t(14;14)(q11;q32),+mar in case 2. Fluorescence in situ hybridization (FISH) and
      sequential R-banding FISH assay with dual-color break-apart IGH probe confirmed
      that t(14;14)(q11;q32) involved the IGH gene in our cases. The results indicate
      that the t(14;14)(q11;q32) involving IGH at 14q32 in B-lineage ALL in our cases
      differ from those reported to involve the TCL1 gene on 14q32.1 in T-cell leukemia
      associated with AT. Sequential R-banding and FISH provide precise analysis of
      alterations of chromosomes and genes involved.

PMID- 15262435
TI  - Chronic lymphocytic leukemia in the course of chronic myelocytic leukemia:
      evidence of independent clonal origin as shown by interphase fluorescence in situ
      hybridization and fluorescence-activated cell sorting.
AB  - We report the case of a 57-year-old man who developed chronic lymphocytic
      leukemia (CLL) several months after the initial diagnosis of Philadelphia (Ph)
      chromosome-positive (Ph(+)) chronic myelocytic leukemia. CLL cells were purified
      by using fluorescence-activated cell sorting and further analyzed using
      interphase fluorescence in situ hybridization with probes to detect the BCR/ABL
      fusion gene. We provide evidence that the CLL cells arose in a Ph(-) clone.

PMID- 15262436
TI  - X chromosome insertion in the MLL gene in a case of childhood acute myeloblastic
      leukemia.
AB  - Band 11q23 is known to be involved in translocations and insertions with a
      variety of partner chromosomes. These lead to MLL rearrangement, resulting in a
      fusion with numerous genes. We report here the case of a 5-month-old boy
      presenting with hemianopsia and severe diffuse intravascular coagulopathy in whom
      a diagnosis of acute myeloblastic leukemia (AML) French-American-British M4
      classification was made. Conventional cytogenetic techniques showed an ins(11;X)
      (q23;q28q12). Fluorescent in situ hybridization (FISH) with whole chromosome
      paints confirmed this finding. Using a specific probe, the MLL gene was found to
      be disrupted, a portion of the X chromosome being inserted between the 5' and 3'
      regions of the MLL gene. Although some cases of insertion involving chromosomes X
      and 11 have been reported in AML, this appears to be the first case involving
      band Xq28. We postulate that this chromosomal rearrangement led to the fusion of
      the 5' region of the MLL gene with a yet unidentified gene located in band Xq28.

PMID- 15262437
TI  - Chromosomal aberrations in Korean nonsmall cell lung carcinomas: degenerate
      oligonucleotide primed polymerase chain reaction comparative genomic
      hybridization studies.
AB  - Chromosomal aberrations were investigated in 48 Korean nonsmall cell carcinomas
      of the lung (NSCLC), by degenerate oligonucleotide primed polymerase chain
      reaction comparative genomic hybridization. These included 16 adenocarcinomas, 27
      squamous cell carcinomas (SCCs), and 5 large-cell carcinomas. The common sites of
      copy number increases were 3q26 approximately qter (23 cases, 48%); 8q23
      approximately qter (46%); 20q13.1 (42%); 1q42 approximately qter (38%); 3q25
      (38%); 21q22 (38%); and 22q13 (38%). DNA amplification was identified in 19
      carcinomas (40%), and the frequent sites of amplification were 8q24 (seven
      cases), 3q26 (seven cases), and 3q27 (seven cases). The frequently under
      represented chromosomal regions were Yq (38%), 4q25 approximately q26 (23%), and
      4q31 (23%). In particular, gains of 3q26 approximately qter (74%), 15q (56%), and
      19q (59%) and loss of 13q22 approximately q31 (26%) were more frequently detected
      in SCCs of the lung. These nonrandom aberrations can serve as starting points for
      the identification of potential oncogenes/tumor suppressor genes related to the
      tumorigenesis of Korean NSCLC.

PMID- 15262438
TI  - Trisomy 4 as the sole cytogenetic abnormality in a patient with T-cell acute
      lymphoblastic leukemia.
AB  - Trisomies as sole cytogenetic abnormalities are extremely rare in acute
      lymphoblastic leukemia (ALL). We describe here the clinical features and
      immunophenotyping, cytogenetic, and fluorescence in situ hybridization (FISH)
      findings in a T-cell ALL patient with trisomy 4 as the sole cytogenetic
      abnormality. The leukemic clone was positive for CD2, CD7, CD34, and terminal
      deoxynucleotidyl transferase (TdT); CD13 was weakly expressed. Data on the
      tracking of the leukemic clone with immunophenotyping, cytogenetic, and FISH
      studies are discussed. The present case is compared with the three previous
      reported cases of trisomy 4 in ALL. Due to the rarity of this cytogenetic
      abnormality, its prognostic significance in ALL remains unclear.

PMID- 15262439
TI  - Identification of chromosomal changes with comparative genomic hybridization in
      sporadic breast cancer in Mexican women.
AB  - Breast cancer is the second leading cause of death in women older than 35 years
      in Mexico. In this study, we used comparative genomic hybridization (CGH) to
      analyze sporadic breast cancers at stages II and III from untreated patients. We
      obtained 4.1 chromosomal alterations per sample, less than in previous reports.
      We identified a small region in Xq27 with high-level amplification in 3 of 16
      samples. This amplification has been reported only in pancreatic and gastric
      cancer cell lines and in testis tumors; in addition, this amplification had been
      reported in one primary breast cancer, but in a more extended region that we
      identified. We also identified a loss in 2p13, not previously reported in this
      neoplasia. The most frequent alterations were amplifications in 4q, 5q, 8q, 12p,
      and 13q and losses in 1p, 8p, 16p, 19q, and Xp. CGH provides data for better
      understanding of molecular events in this neoplasia.

PMID- 15262440
TI  - Differential diagnosis of congenital fibrosarcoma.

PMID- 15262441
TI  - Unbalanced t(2;19) and t(2;16) in a neurofibroma.

PMID- 15262442
TI  - AML1/RUNX1 fusion gene and t(5;21)(q13;q22) in a case of chronic myelomonocytic
      leukemia with progressive thrombocytopenia and monocytosis.

PMID- 15262443
TI  - Trisomy 14 in acute myeloid leukemia with ringed sideroblasts.

PMID- 15262444
TI  - Remission of acute monocytic leukemia, secondary to treatment with
      epipodophyllotoxins, in a patient with t(8;16)(p11;p13) and MYST3-CREBBP fusion.

PMID- 15262445
TI  - A modified quantitative EMSA and its application in the study of RNA--protein
      interactions.
AB  - Electrophoretic mobility shift assay (EMSA) is used to detect the complex of
      protein and nonradioisotope-labeled probe qualitatively. In this paper, we
      describe a modified quantitative EMSA, which uses biotin-labeled RNA in the
      complex formation. The RNA-protein complex is separated by agarose gel
      electrophoresis and capillary transferred to a positively charged nylon membrane.
      It is then detected through a secondary detection system using 5-bromo-4-chloro-3
      indolyl phosphate (BCIP)-nitroblue tetrazolium (NBT) as the colorimetric
      precipitating substrate. After scanning and quantification by an image analysis
      program, ImageQuant, it was observed that the optical density of the bands was
      proportional to the decadic logarithm value of standard RNA quantities in the
      tested range. By using the standard curve of the optical densities plotted
      against the logarithm values of RNA quantities in the linear range, we can
      calculate RNA quantities according to the optical density of the band and make a
      quantitative analysis of EMSA. This method was applied successfully in the study
      of the interactions between the AU-rich element (ARE) and HuR, which is one of
      the human members of the (embryonic lethal abnormal vision) ELAV family. The
      results reveal that the biotin-labeled AUFL transcripts in the RNA-protein
      complex can be detected quantitatively, while maintaining the biological features
      of its binding ability to the HuR protein. By this method, it is possible to
      conduct qualitative and quantitative analyses of the EMSA in the study of RNA
      protein interactions.

PMID- 15262446
TI  - Characterization of small unilamellar vesicles using solvatochromic pi*
      indicators and particle sizing.
AB  - A suite of small unilamellar vesicles (SUVs) composed of mixtures of
      phospholipids and cholesterol (CH) or the synthetic surfactant dihexadecyl
      phosphate (DHP) and cholesterol was investigated using a homologous series of
      solvatochromic pi* indicators coupled with size exclusion methods and photon
      correlation spectroscopy (PCS). The solvatochromic method, which is based on the
      measurement of solvent-dependent shifts in lambda(max) from UV-Vis spectra of
      solubilized indicators, was used to quantify the dipolarity and polarizability
      (pi*) of probe solvation environments. The partitioning of the series of
      individual di-n-alkyl-p-nitroaniline (DNAP) pi* indicators in
      PG(24)PC(46)Chol(30) and DHP(70)Chol(30) SUVs was examined as a function of the
      head group structure as well as the method of dye-vesicle preparation.
      Solubilization of the larger more hydrophobic probes in the bilayer portion of
      PG(24)PC(46)Chol(30) SUVs was aided through physical entrapment. Such physical
      methods were not needed for the smaller indicators or for the range of indicators
      in the DHP(70)Chol(30) dispersions. Extrusion and size-exclusion chromatographic
      methodologies for the preparation of physically entrapped dopants in SUVs of
      fixed size range demonstrated that the larger (longer alkyl chain) dopants in the
      series resided in PG(24)PC(46)Chol(30) liposomes with a wider range of sizes,
      while the smaller more polar solutes tended to be entrapped in smaller vesicles
      with a narrower size range.

PMID- 15262447
TI  - Low microwave-amplitude ESR spectroscopy: measuring spin-relaxation interactions
      of moderately immobilized spin labels in proteins.
AB  - Electron spin resonance (ESR) spectroscopy in combination with site-directed spin
      labeling (SDSL) is a powerful tool for determining protein structure, dynamics
      and interactions. We report here a method for determining interactions between
      spin labels and paramagnetic relaxation agents, which is performed under
      subsaturating conditions. The low microwave-field amplitude employed (h(1)<0.36
      G) only requires standard, commercially available ESR equipment. The effect of
      relaxation enhancement on the spin-spin-relaxation time, T(2e), is measured by
      this method, and compared to classical progressive power saturation performed on
      a free spin label, (1-oxyl-2,2,5,5-tetramethyl-Delta(3)-pyrroline-3
      methyl)methanethiosulfonate (MTSL), and a spin-labeled protein (Thermomyces
      lanuginosa lipase, TLL-I252C), employing the water-soluble relaxation agent
      chromium(III) oxalate (Crox) in concentrations between 0-10 mM. The low-amplitude
      theory showed excellent agreement with that of classical power saturation in
      quantifying Crox-induced relaxation enhancement. Low-amplitude measurements were
      then performed using a standard resonator, with Crox, on 11 spin-labeled TLL
      mutants displaying rotational correlation times in the motional narrowing regime.
      All spin-labeled proteins exhibited significant changes in T(2e). We postulate
      that this novel method is especially suitable for studying moderately immobilized
      spin labels, such as those positioned at exposed sites in a protein. This method
      should prove useful for research groups with access to any ESR instrumentation.

PMID- 15262448
TI  - High-throughput method for detecting DNA methylation.
AB  - Aberrant DNA methylation of CpG site is among the earliest and most frequent
      alterations in cancer. Detection of promoter hypermethylation of cancer-related
      gene may be useful for cancer diagnosis or the detection of recurrence. However,
      most of the studies have focused on a single gene only and gave little
      information about the concurrent methylation status of multiple genes. In this
      study, we attempted to develop a microarray method coupled with linker-PCR for
      detecting methylation status of multiple genes in the tumor tissue. A series of
      synthesized oligonucleotides were synthesised and purified to completely match
      with 16 investigated targets. Then they were immobilized on the aldehyde-coated
      glass slide to fabricate a DNA microarray for detecting methylation status of
      these genes. The results indicated that these genes were all methylated in the
      positive control. However, no methylated was found in these genes for the
      negative control. Only p16 and p15 genes were methylated in investigated genes
      for the gastric tumor tissue, whereas others were not methylated. The above
      results were validated by bisulfite DNA sequencing. Our experiments successfully
      demonstrated that the DNA microarray could be applied as a high-throughput tool
      to determine methylation status of the investigated genes.

PMID- 15262449
TI  - Refined quantitative fluorescent PCR of Y-chromosome DNA sequences mosaics in
      Turner's syndrome patients--alternative to real-time PCR.
AB  - BACKGROUND: Real-time polymerase chain reactions (PCRs) are the most frequently
      used techniques for gonosomal mosaics quantification. The primary aim of this
      work is to assess and optimize the refined technique of quantitative fluorescent
      polymerase chain reaction (RQF PCR) in the quantification of Y-chromosome
      sequences in gonosomal mosaics. The method was applied to the analysis of Y
      chromosome sequences (amelogenin gene, AMELX/Y-loci) in peripheral lymphocytes
      and gonadal tissues in Y-positive Turner's syndrome (TS) patients. METHODS: RQF
      PCR was used for molecular quantification, and fluorescent in situ hybridization
      (FISH) technique was used for comparison. RESULTS: Based on a formulated
      calibration curve, DNA mosaics from six Y-positive patients and gonads from one
      patient were deducted. For calculation of rare mosaics, it is possible to take
      advantage of a new empirical formula. FISH results were comparable to RQF PCR.
      CONCLUSION: The sensitivity of RQF PCR brings significant progress in the
      analysis of gonosomal aberrations. RQF PCR also finds applications in prenatal
      diagnostics of maternal contaminations of amniotic fluid and foetal DNA in
      maternal blood and analysis of chimerism in patients after bone marrow
      transplantation. The method is very convenient for determining the number of
      testis-specific protein, Y-linked (TSPY) gene repetitions.

PMID- 15262450
TI  - Novel peptide surface for reversible immobilization of concanavalin A.
AB  - Concanavalin A (Con A) was spontaneously adsorbed on polymyxin B surface. This
      peptide-lectin interaction was strong, K(D)=1.9 x 10(-10), based predominantly on
      creation of hydrophobic bonds, and was completely reversible. Concanavalin A on
      polymyxin B (PmB) retained higher binding capacity for yeast mannan, compared
      with covalently immobilized lectin. Kinetics of mannan-concanavalin A interaction
      were significantly different in dependence on type of concanavalin A
      immobilization.

PMID- 15262451
TI  - A simple stopped assay for fatty acid amide hydrolase avoiding the use of a
      chloroform extraction phase.
AB  - A stopped assay for fatty acid amide hydrolase (FAAH) has been developed, whereby
      the enzyme reaction product ([(3)H]ethanolamine) was separated from substrate
      (anandamide [ethanolamine-1-(3)H]), by differential adsorption to charcoal. The
      assay gave a better extraction efficiency when acidic rather than alkaline
      charcoal solutions were used to stop the reaction, and a very good ratio of
      sample/blank was also seen. The acidic charcoal assay gave the expected
      sensitivities to compounds known to inhibit FAAH (palmitoyltrifluoromethyl
      ketone, arvanil, AM404 and indomethacin). It is concluded that the acidic
      charcoal extraction method provides a robust and simple stopped assay for FAAH
      without the need to use potentially hazardous solvents like chloroform.

PMID- 15262452
TI  - A comparison of the effects of thiazolidinediones and metformin on metabolic
      control in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus is a condition characterized by impaired
      insulin secretion and resistance to insulin-mediated glucose uptake and
      utilization. A number of oral antidiabetic medication are available for its
      treatment, including metformin and the thiazolidinediones (TZDs). The TZDs have
      been shown to improve insulin resistance, and it has been suggested that
      metformin has similar effects. Although both types of agents improve glycemic
      control, their mechanisms of action and effects on metabolic processes differ.
      OBJECTIVE: The goal of this review was to compare the effects of TZDs and
      metformin on metabolic control in patients with type 2 diabetes. METHODS: A
      search of MEDLINE to March 2004 using the terms metformin and biguanides, and
      thiazolidinediones and glitazones was conducted to identify preclinical and
      clinical studies focusing on the mechanisms of action and comparative effects of
      TZDs and metformin. Also searched were published abstracts from recent major
      diabetes and endocrinology conferences. RESULTS: In the studies reviewed, both
      TZDs and metformin demonstrated the ability to improve glycemic control, although
      long-term monotherapy with TZDs appeared to be more effective than metformin.
      There continues to be debate about whether metformin is more effective than TZDs
      in terms of inhibition of hepatic glucose production. However, various studies
      have found TZDs to be more effective in promoting an increase in whole-body
      insulin sensitivity. With respect to lipid metabolism, patients who received TZDs
      had a greater reduction in concentrations of both plasma triglycerides and free
      fatty acids. Metformin was more effective in promoting weight loss in patients
      with type 2 diabetes, although TZDs may decrease visceral fat levels. Treatment
      with either metformin or TZDs was associated with a reduction in the risk of
      cardiovascular disease, although the mechanisms by which they accomplished this
      seem to differ. CONCLUSIONS: The evidence suggests that the predominant effect of
      metformin is inhibition of hepatic glucose production, whereas the primary
      effects of TZDs is reduction of insulin resistance and promotion of peripheral
      glucose uptake. TZDs appear to have more positive effects on other metabolic
      processes and to be associated with greater improvements in cardiovascular risk
      factors compared with metformin.

PMID- 15262453
TI  - Is there a place for epoetin alfa in managing anemia during critical illness?
AB  - BACKGROUND: Anemia is a common problem in critically ill patients. As a result,
      blood transfusions are often used in the intensive care unit (ICU) setting.
      However, mounting evidence shows that blood transfusions may contribute to
      negative outcomes, such as transfusion-related infections, organ dysfunction, and
      immunosuppression. Supplementation with epoetin alfa is currently used in some
      medical centers to manage anemia in critically ill patients. OBJECTIVE: This
      review discusses the risks with blood transfusions and the clinical evidence
      supporting the use of epoetin alfa in managing edema during critical illness.
      METHODS: A search was conducted in MEDLINE and Current Contents (1966-2003) using
      the terms epoetin alfa, recombinant human erythropoietin, and anemia. Articles
      addressing anemia and the use of epoetin alfa in critically ill patients were
      selected and assessed. From this selection, the cited references addressing the
      etiology of anemia in the ICU and the risks associated with blood transfusions
      were manually extracted and reviewed. RESULTS: Several reports have shown that
      critically ill patients display evidence of anemia due to a blunted
      erythropoietin response. One large, randomized, placebo-controlled study assessed
      the effect of SC epoetin alfa on blood transfusions in the ICU. In this study,
      40, 000 IU administered weekly for up to 4 weeks resulted in an overall
      transfusion reduction (9.9% absolute risk reduction; P<0.001 ). Other, smaller
      studies using different dosing regimens in critically ill patients have also
      demonstrated that epoetin alfa can decrease the need for transfusion. CONCLUSION:
      The use of epoetin alfa in critically ill patients can decrease the number of
      blood transfusions required during hospitalization, and potentially result in
      transfusion avoidance. Because of the scarce amount of evidence and the diversity
      of dosing regimens used used, no strict recommendations can be drawn from this
      review.

PMID- 15262454
TI  - Role of raloxifene in breast cancer prevention in postmenopausal women: clinical
      evidence and potential mechanisms of action.
AB  - BACKGROUND: Raloxifene is a selective estrogen-receptor modulator (SERM)
      indicated for the prevention and treatment of osteoporosis in postmenopausal
      women. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, an
      osteoporosis treatment trial, raloxifene therapy was associated with a reduced
      incidence of invasive, estrogen receptor (ER)-positive breast cancer compared
      with placebo (relative risk, 0.16; 95% CI, 0.09-0.30). OBJECTIVE: This review
      summarizes available preclinical and clinical data pertaining to a potential role
      for raloxifene in the prevention of breast cancer, and examines the mechanisms of
      action by which raloxifene may exert an effect. METHODS: Relevant articles were
      identified through a search of MEDLINE for English-language studies published
      between 1966 and January 2003. Search terms included raloxifene, keoxifene,
      tamoxifen, SERM, estrogen, estrogen receptor, breast, mammary, growth factors,
      and apoptosis. The reference lists of identified articles were reviewed for
      additional publications. RESULTS: Both preclinical and clinical data suggest a
      role for raloxifene in the prevention of breast cancer. Like tamoxifen,
      raloxifene acts as an estrogen antagonist in breast tissue through competitive
      binding to the ER. Raloxifene may also inhibit breast tissue proliferation
      through mechanisms independent of the ER. CONCLUSIONS: Given raloxifene's
      mechanism of action and the preclinical evidence for its role in breast cancer
      prevention, a clinically favorable effect seems feasible. Results of ongoing
      clinical studies will provide evidence to support or refute the clinical findings
      of MORE and thus raloxifene's role in the breast cancer prevention.

PMID- 15262455
TI  - Teriparatide: a review.
AB  - BACKGROUND: Traditionally, the management of osteoporosis in men and women has
      included the use of antiresorptive agents in combination with calcium and vitamin
      D supplementation. The mechanism of action of teriparatide is unique in that it
      possesses anabolic properties and therefore builds bone. Since the approval of
      teriparatide in the United States in 2002, a great deal of interest regarding its
      use in osteoporosis has developed. OBJECTIVES: This article reviews the
      information available on the new recombinant human parathyroid hormone
      teriparatide (hPTH [1-34]), including its clinical pharmacology, mechanism of
      action, pharmacokinetic properties, clinical efficacy, safety profile, potential
      drug interactions, contraindications and warnings, dosage and administration, and
      pharmacoeconomics. METHODS: The articles included in this review were identified
      through searches of PubMed and MEDLINE (1966-December 2003) and International
      Pharmaceutical Abstracts (1970-December 2003). Search terms included
      teriparatide, Forteo, recombinant human parathyroid hormone (1-34), and
      osteoporosis. The references of the identified articles were reviewed for
      additional publications. Specific product information was also obtained from the
      manufacturer of teriparatide. RESULTS: Teriparatide has been studied in
      postmenopausal women with osteoporosis, drug-induced osteoporosis (specifically,
      corticosteroid-induced osteoporosis), and men with osteoporosis. The data
      available from various clinical trials have shown an increase in both bone
      mineral density (BMD) and bone mineral content (BMC) with the use of teriparatide
      compared with placebo. One study found that women treated with the 20-microg dose
      and the 40-microg dose were 35% and 40%, respectively, less likely to have one or
      more new nonvertebral fractures compared with placebo (P = 0.02). Another study
      compared the use of daily teriparatide 40-microg injections versus oral daily
      alendronate. Results showed that the incidence of nonvertebral fractures was
      significantly lower in the teriparatide group than the alendronate group (P <
      0.05). A study using 20- and 40-microg daily injections of teriparatide was
      performed in men with osteoporosis. There was a statistically significant
      increase in lumbar spine BMD of 5.9% in the 20-microg group and 9.0% in the 40
      microg group (both, P < 0.001). In the femoral neck, a 1.5% increase in BMD
      occurred in the 20-microg group (P = 0.021) and a 0.9% increase in the 40-microg
      group (P < 0.001). A limited number of studies are available assessing the
      combination of antiresorptive medications and teriparatide; however, the
      available data suggest that the effects of teriperatide do not require prior
      stimulation of bone resorption. CONCLUSIONS: Teriparatide has been shown
      clinically to improve BMD and BMC in postmenopausal women and in men. Because of
      its anabolic capabilities, teriparatide can be used as an alternative to the
      traditional therapies that are currently available for the treatment of
      osteoporosis, with scheduled monitoring for adverse effects such as hypercalcemia
      and urinary calcium excretion. In 1 study, mild hypercalcemia was seen most often
      4 to 6 hours after SC injection of teriparatide before returning to normal.
      Urinary calcium was observed to increase by 30 mg/d (0.75 mmol/d) with
      teriparatide.

PMID- 15262456
TI  - Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in
      combination with a diuretic, for the treatment of hypertension: the Blood
      Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril
      (PREVAIL) study.
AB  - BACKGROUND: The goal of antihypertensive therapy is to provide good blood
      pressure (BP) control without eliciting adverse effects. OBJECTIVE: This study
      compared the risk-benefit profile of the angiotensin II receptor blocker
      valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in
      patients with mild to severe hypertension. The primary objective was to show that
      the equipotent BP-lowering effect of the valsartan-based treatment is accompanied
      by a better tolerability profile. METHODS: This 16-week, randomized, double
      blind, parallel-group study was conducted at 88 outpatient centers across Italy.
      After a 2-week placebo run-in period, patients aged > or = 18 years with mild to
      severe hypertension (systolic BP [SBP], 160-220 mm Hg; diastolic BP [DBP], 95-110
      mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self
      administered treatment with valsartan 160-mg capsules or lisinopril 20-mg
      capsules under double-blind conditions for 4 weeks. Responders continued
      monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the
      final 12 weeks of the study. The 2 primary variables used to assess the
      equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and
      sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of
      drug-related adverse events (AEs) was used to assess whether 1 treatment had a
      better tolerability profile than the other. Tolerability was assessed by
      collecting information about AEs by means of questioning the patient or physical
      examination at each visit. RESULTS: A total of 1213 patients were enrolled (635
      men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28-78 years]). The study
      was completed by 1100 patients (553 receiving valsartan and 547 receiving
      lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (10.2%)
      [corrected] treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and
      23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments
      were similarly effective in reducing sitting BP, with mean SBP/DBP reductions of
      31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively. At the end of the study, BP
      was controlled in 82.6% [corrected] of the patients receiving valsartan and 81.6%
      of those receiving lisinopril. AEs were experienced by 5.1% of the patients
      treated with valsartan and 10.7% of those treated with lisinopril (P=.0001), with
      dry cough observed in 1.0% and 7.2% of patients, respectively (P<0.001).
      CONCLUSIONS: Valsartan and lisinopril were both highly effective in controlling
      BP in these patients with mild to severe hypertension, but valsartan was
      associated with a significantly reduced risk for AEs, especially cough.

PMID- 15262457
TI  - Treatment of vertigo due to acute unilateral vestibular loss with a fixed
      combination of cinnarizine and dimenhydrinate: a double-blind, randomized,
      parallel-group clinical study.
AB  - BACKGROUND: Acute unilateral vestibular loss is a balance disorder that is
      accompanied by vertigo symptoms and concomitant vegetative symptoms, including
      nausea and vomiting. Patients are frequently confined to bed rest but may
      continue to experience vertigo symptoms. A well-established antivertiginous
      therapy consisting of cinnarizine and dimenhydrinate at low doses may offer rapid
      relief of acute vertigo symptoms due to acute vestibular loss, without inhibiting
      physiological compensation processes. OBJECTIVE: The purpose of this study was to
      compare the clinical efficacy and tolerability of a fixed combination of
      cinnarizine 20 mg and dimenhydrinate 40 mg versus monotherapy with its respective
      components in the treatment of acute vertigo symptoms due to acute unilateral
      vestibular loss. METHODS: In this prospective, single-center, randomized, double
      blind, parallel-group clinical study, 50 patients with acute vestibular vertigo
      were randomly assigned to receive 4 weeks of treatment (1 tablet 3 times daily)
      with a fixed combination of 20 mg cinnarizine and 40 mg dimenhydrinate, 20 mg
      cinnarizine alone, or 40 mg dimenhydrinate alone. All patients received a 15%
      mannitol infusion as standard therapy during the first 6 days of treatment.
      Efficacy was determined by the patients' assessments of vertigo symptoms after 1
      and 4 weeks of treatment using a verbal rating scale (vertigo score) and by
      vestibulo-ocular and vestibulospinal tests. The primary efficacy criterion was
      defined as the relief of vertigo symptoms after 1 week of treatment. RESULTS:
      After 1 week of treatment, the fixed combination was significantly more effective
      than 20 mg cinnarizine (P < 0.001) and 40 mg dimenhydrinate (P < 0.01). After 4
      weeks, the fixed combination was still significantly more effective than
      cinnarizine in reducing vertigo symptoms (P < 0.01) and significantly more
      effective than dimenhydrinate in improving the patients' balance while standing
      (P < 0.05). The tolerability of the fixed combination was rated good or very good
      by 100% of the patients (cinnarizine alone, 82.4%; dimenhydrinate alone, 94.4%).
      No serious adverse events occurred. Four patients in the fixed combination and
      the cinnarizine groups, and 6 patients in the dimenhydrinate group reported
      nonserious adverse events. CONCLUSIONS: The results of this study suggest a
      distinct benefit in using a fixed combination of cinnarizine 20 mg and
      dimenhydrinate 40 mg versus the respective monotherapies in this population of
      patients with acute vestibular vertigo.

PMID- 15262458
TI  - A randomized, open-label, comparative study of simvastatin plus diet versus diet
      alone on angiographic retardation of coronary atherosclerosis in adult Japanese
      patients: Japanese utilization of simvastatin therapy (JUST) study.
AB  - BACKGROUND: Cholesterol-lowering therapy reduces the risk of cardiovascular
      events by slowing the progression or enhancing the regression of coronary
      atherosclerosis. OBJECTIVE: This study assessed the effects of simvastatin 10
      mg/d on progressive coronary atherosclerosis in Japanese patients with coronary
      artery disease and mild to moderate hypercholesterolemia. METHODS: In a 2-year,
      open-label comparative study, patients with coronary atherosclerotic lesions (>
      or =50% diameter stenosis) and serum total cholesterol levels > or =200 and < or
      =280 mg/dL were randomly assigned to 2 groups: 1 group received simvastatin 10
      mg/d taken orally with diet (S-D) and the other group was assigned to diet alone
      (D). Atherosclerotic progression in coronary segments was compared in the 2
      groups using quantitative coronary angiography (QCA). QCA measurements were done
      under blinded conditions. The study's primary end point was the comparison of
      mean changes in each segment's minimum obstruction diameter (MOD) or mean segment
      diameter (MSD) between the S-D group and the D group. RESULTS: A total of 299
      patients were randomized, 146 to the S-D group and 153 to the D group. Mean (SD)
      age was 58.7 (8.0) years and mean (SD) total cholesterol level was 232.6 (21.6)
      mg/dL at baseline. After 2 years, serum low-density lipoprotein cholesterol
      levels decreased by 31.9% in the S-D group and by 2.0% in the D group. QCA showed
      significant stenotic progression in the D group, with reductions in MOD and MSD
      both by per-segment-based (P < 0.001 and P = 0.004, respectively) and per-patient
      based (both P = 0.004) analyses. Although simvastatin treatment suppressed
      atherosclerotic progression in both per-segment- and per-patient-based analyses,
      significant reductions were found only in MOD values with per-segment-based
      analyses (P = 0.034). In a categorical approach, progression was found in
      significantly fewer segments in the S-D group compared with the D group (MOD, P =
      0.014; MSD, P = 0.003), with odds ratios (S-D) group/D group) of 0.571 for MOD
      and 0.390 for MSD. Significantly fewer patients with angiographic progression
      were observed in the S-D group (23.3%) compared with the D group (39.4%) with
      respect to MSD (P = 0.02). CONCLUSION: Two years of treatment with simvastatin 10
      mg/d improved patients' lipid profile and retarded coronary atherosclerotic
      progression in Japanese patients with coronary artery disease and mild to
      moderate hypercholesterolemia

PMID- 15262459
TI  - New strategies for basal insulin treatment in type 2 diabetes mellitus.
AB  - BACKGROUND: The clinical progression of type 2 diabetes mellitus (DM) is well
      understood. Glycemic control gradually deteriorates, and progression of DM
      eventually leads to an increased risk for microvascular and macrovascular
      complications. Reassessment of current insulin treatment strategies leading to
      restoration of glycemic control is essential to prevent or stop the progression
      of type 2 DM and its complications. OBJECTIVE: The purpose of this article was to
      review the importance of instituting a strategy of basal insulin therapy in
      patients with type 2 DM. METHODS: Relevant articles were obtained through an
      online search of PubMed and MEDLINE for literature published from 1990 to 2003.
      The search terms used were insulin therapy, combination oral therapy, treatment
      failure, glycemic control, insulin analogues, insulin glargine, basal insulin,
      and microvascular complications. RESULTS: Large-scale intervention trials, such
      as the United Kingdom Prospective Diabetes Study (UKPDS), have reported that
      patients with type 2 DM treated with oral combination therapy are unable to
      maintain glycemic control. These observations have led to a reassessment of the
      role of insulin therapy in type 2 DM. The importance of tight glycemic control
      through the aggressive use of insulin early in the course of the disease is
      apparent from the UKPDS, Diabetes Control and Complications Trial, and other,
      smaller studies. Considerable evidence indicates that initiating a basal insulin
      replacement strategy with an existing oral regimen can result in regaining
      glycemic control. Evidence emerging from recent studies indicates that use of
      intensive insulin therapy early in the course of the disease may have a positive
      clinical impact on outcome and slow the progression of complications. The
      availability of basal insulin analogues has expanded treatment options and
      improved the efficacy of therapeutic regimens for type 2 DM. CONCLUSIONS: The
      available data suggest using an earlier transition from monotherapy to
      combination therapy to minimize disease-associated morbidity. The availability of
      new insulin analogues has expanded therapeutic options and offers the potential
      to enhance the efficacy of therapeutic regimens for type 2 DM as well as improve
      the ease and safety of treatment when glycosylated hemoglobin cannot be
      maintained <7% on > or =1 oral antidiabetic agent.

PMID- 15262461
TI  - Results of a naturalistic study of treatment options: switching atypical
      antipsychotic drugs or augmenting with valproate.
AB  - BACKGROUND: Combination therapy with atypical antipsychotic agents has not been
      well studied. Duration of persistence with a prescribed treatment regimen can be
      used to estimate overall treatment success. OBJECTIVE: The aim of this study was
      to determine whether valproate augmentation improved treatment efficacy (ie,
      persistence with the prescribed regimen) and efficacy (ie, reduction of
      antipsychotic dose) with atypical antipsychotic drugs for older and younger
      patients, using a retrospective database analysis. METHODS: Prescription refill
      data for atypical antipsychotics during calendar-year 2001 from a national
      pharmacy chain was used for longitudinal analyses. The database was used to
      identify patients aged 15 to 64 years and > or =65 years taking risperidone,
      quetiapine, or olanzapine (but not valproate). Patients who switched to another
      atypical antipsychotic (group A) or added valproate (group B) were followed after
      the index prescription to determine the duration of persistence with the
      treatment regimen and dose changes. RESULTS: We identified 10,262 patients who
      were prescribed an atypical antipsychotic, of whom 1022 patients switched to an
      alternative atypical and 1651 added valproate to the index atypical. The addition
      of valproate provided significantly longer duration of treatment regimen (mean,
      155-159 days) than switching from any atypical antipsychotic drug (mean, 127-130
      days) for patients aged 15 to 64 years or > or =65 years (all P<0.001). Atypical
      antipsychotic doses did not change significantly from baseline to final
      prescription in groups A or B. The final mean (SD) dose of valproate added to
      risperidone (389.1 [130.7] mg/d) was significantly lower than valproate added to
      quetiapine (424.6 [117.1] mg/d; P=0.002) or olanzapine (411.6 [122.8] mg/d;
      P=0.007). CONCLUSIONS: In this naturalistic study, the addition of valproate to
      an atypical antipsychotic increased the duration of treatment compared with
      switching among atypical antipsychotics. Valproate augmentation may be a good
      treatment strategy for patients whose atypical antipsychotic monotherapy is
      inadequate.

PMID- 15262462
TI  - Review of antibiotic drug use in a surgical ICU: management with a patient data
      management system for additional outcome analysis in patients staying more than
      24 hours.
AB  - BACKGROUND: A number of developments have been made in computerized patient data
      management systems (PDMSs), making them of interest to medical and nursing staff
      as a means of improving patient care. OBJECTIVES: The aim of this study was to
      assess the capability of a PDMS to record and provide drug-administration data
      and to investigate whether the PDMS may be used as a means of support for
      clinical audits and quality control. Furthermore, we assessed whether antibiotic
      therapy as a surrogate for infections correlates with hospital mortality in
      patients staying >24 hours in a surgical intensive care unit (SICU). METHODS:
      Because of its medical and economic importance in ICU treatment, we chose to use
      the field of antibiotic therapy as an example. A PDMS was used in a 14-bed SICU
      (Department of Anesthesiology, Intensive Care Medicine, and Pain Therapy,
      University Hospital Giessen, Giessen, Germany) to record relevant patient data,
      including therapeutic, diagnostic, and nursing actions. During a 15-month period
      (April 1, 2000 to June 30, 2001), antibiotic drug therapy was electronically
      analyzed and presented using the anatomic therapeutic chemical (ATC) category for
      antibacterials (ATC group, J01) with daily defined doses. Furthermore, the
      correlation of antibiotic therapy with patient outcome (hospital mortality) was
      tested using logistic regression analysis. RESULTS: A total of 2053 patients were
      treated in the SICU. Of these, 58.0% (1190 patients) received antibiotics (4479
      treatment days; 13,145 single doses). Cephalosporins (ATC category, J01DA) were
      used most frequently (1785 treatment days [39.9% of treatment days]), followed by
      combinations of penicillins with beta-lactam inhibitors (ATC category, J01CR;
      1478 treatment days [33.0%]) and imidazole derivatives (ATC category, J01XD; 667
      treatment days [14.9%]). The antibiotic therapy lasted <3 days in 65.6% of cases.
      In 13.8% of cases, the treatment lasted >1 week. A total of 36.7% of cases were
      treated with only 1 antibiotic agent, 14.1% were given a combination of 2, and
      7.2% were given a combination of > or =3 antibiotic agents. Seven hundred twenty
      six patients remained in the SICU for >24 hours; 143 (19.7%) died during their
      hospital stay; 110 (15.2%) in the SICU. The duration of antibiotic therapy (odds
      ratio [OR], 1.46) and number of different antibiotic drugs used (OR, 2.15)
      significantly correlated with hospital mortality. CONCLUSIONS: Antibiotic therapy
      in a SICU can be assessed and analyzed in detail using a PDMS. Furthermore, in
      this study, the duration of antibiotic therapy and the number of antibiotic
      agents used correlated with hospital mortality. In further developing PDMSs, it
      is important for quality-assurance purposes to document the reasons for giving
      antibiotics and for changing prescriptions. It would also be helpful to integrate
      certain therapy standards and reminder functions for the duration of therapy in
      the PDMS.

PMID- 15262463
TI  - Evaluating the quality of life of patients with restless legs syndrome.
AB  - BACKGROUND: The primary morbidities of restless legs syndrome (RLS) involve sleep
      loss, extreme discomfort, and disruption of normal activities. Although the
      condition is not life-threatening, assessing the disease burden and the impact of
      RLS on quality of life (QOL) is critical for evaluating treatment benefits.
      OBJECTIVE: The purpose of this study was to assess the impact of RLS on QOL.
      METHODS: In this subanalysis of a specific validation study, the SF-36 (Medical
      Outcomes Study 36-Item Short Form health survey) was administered to 85 patients
      with primary RLS who had been referred to a sleep-medicine clinic. The scores
      were compared with published norms for the general population (N = 2474).
      RESULTS: The majority (63.5%) of RLS patients were women; the mean (SD) age was
      62.4 (14.0) years; 67.1% of patients experienced RLS symptoms almost daily. The
      RLS group, particularly patients with more severe RLS, reported significant
      deficits (10-40 points on 100-points scales) in physical functioning, bodily
      pain, role functioning, mental health, general health, and vitality compared with
      the general population. The RLS sample had significantly lower scores (worse QOL)
      on all 8 scales of the SF-36 compared with patients with hypertension (P<0.01);
      compared with patients with other cardiovascular conditions (ie, congestive heart
      failure, myocardial infarction within the past year, and angina), the RLS group
      had lower scores on 6 of the 8 scales. RLS patients had lower scores on 7 of 8
      scales compared with diabetes patients, and on 4 of 8 scales compared with
      osteoarthritis patients. CONCLUSIONS: Comparison of the SF-36 scores of patients
      with RLS and the normative general population suggests that the disorder has a
      significant impact on patient QOL.

PMID- 15262464
TI  - P.o. versus i.m. cobalamin treatment in megaloblastic anemia.

PMID- 15262466
TI  - Glucose permeable poly (dimethyl siloxane) poly (N-isopropyl acrylamide)
      interpenetrating networks as ophthalmic biomaterials.
AB  - Poly (dimethyl siloxane) (PDMS) has been widely used as a biomaterial in
      ophthalmic and other applications due to its good compatibility, high mechanical
      strength, excellent oxygen permeability and transparency. However, for use as an
      artificial cornea, contact lens and in other applications, modifications with
      hydrophilic functional groups or polymers are necessary to improve wettability
      for tear protein and mucin interactions and to improve glucose permeability for
      cellular health. Poly (N-isopropyl acrylamide) (PNIPAAM) is a biocompatible and
      hydrophilic polymer that has been extensively studied on controlled drug release
      applications due to its lower critical solution temperature (LCST) phenomenon. In
      the current work, a composite interpenetrating network (IPN) of PDMS and PNIPAAM
      was formed to generate polymers with oxygen and glucose permeability as well as
      improved wettability compared to PDMS homopolymers and greater mechanical
      strength than PNIPAAM homopolymers. Transparent vinyl and hydroxyl terminated
      PDMS/PNIPAAM IPNs (PDMS-V and PDMS-OH IPNs, respectively) were successfully
      synthesized. Transmission electron microscopy images verified the structure of
      the IPNs. Surface analysis suggested that PNIPAAM was present on the surface as
      well as in the bulk material. PDMS-OH IPNs generated from a PDMS-OH matrix cured
      in the presence of solvent had the highest glucose permeability at 10(-7)cm2/s,
      comparable to that of the native cornea. The LCST phenomenon remained in these
      materials, although changes were not as abrupt as with pure PNIPAAM. These
      results suggest that these materials may be further developed as ophthalmic
      biomaterials or for controlled drug-release applications.

PMID- 15262467
TI  - The effect of temperature on the nucleation of corrosion pits on titanium in
      Ringer's physiological solution.
AB  - This paper describes the effect of temperature on the nucleation of corrosion
      pits on titanium microelectrodes in Ringer's physiological solution. The results
      are shown for potentials far below the pitting potential, and describe breakdown
      of passivity with no permanent propagation of pits. Nucleation events could be
      observed at all the temperatures used, although they were very rare events at 20
      degrees C. The frequency of breakdown rises significantly with increase in
      temperature. Examples are shown of current transients due to both pit nucleation
      and to metastable pit propagation, the latter being rare events. Analysis shows
      that these events constitute a significant fraction of the passive corrosion rate
      of titanium.

PMID- 15262468
TI  - A 3D analysis of mechanically stressed dentin-adhesive-composite interfaces using
      X-ray micro-CT.
AB  - Dentin bonding systems (DBS) have been developed in order to bond restorative
      materials (i.e. composite) to tooth tissues when function and integrity have to
      be re-established. Adhesion to dentin results from the penetration of DBS into
      the demineralised substrate constituted by a conditioned collagen network. The
      long-term stability of a restored tooth is mainly affected by the seal of the
      restorative material on the dental structures. Although leakage through the
      dentin-DBS interface has been widely reported, 3D investigation technique and
      accurate non-destructive measurements of leakage as functions of mechanical
      cycling have never been provided. To address these issues, the properties of the
      material interface are analysed using micro-tensile static and dynamic tests,
      assisted by the finite element modelling and by the X-ray computed micro
      tomography. The dual energy absorption technique, with the synchrotron beam
      light, has been developed to investigate, in a non-destructive manner, the effect
      of mechanical cycling on leakage of a silver nitrate staining solution at the
      dentin-DBS interface. The effect of the pulpal roof on the stress distribution in
      the coronal dentin-DBS-composite interface has been investigated and the level at
      which the state of stress can be assumed to be uniform within acceptable limits
      has been defined. The tensile static and dynamic results suggest that the
      adhesive strength for the multi-step DBS resulted significantly higher than the
      other investigated DBS. Imaging results indicate that 3D leakage occurs radially
      at the dentin-adhesive interface through the interface itself rather than through
      the unconditioned dentin bulk; moreover, the dynamic tensile loading allows a
      more diffuse staining penetration.

PMID- 15262469
TI  - Nanoscale variation in surface charge of synthetic hydroxyapatite detected by
      chemically and spatially specific high-resolution force spectroscopy.
AB  - The normal intersurface forces between nanosized probe tips functionalized with
      COO-- and NH3+-terminated alkanethiol self-assembling monolayers and dense
      polycrystalline phase pure synthetic hydroxyapatite (HA) were measured via a
      powerful nanomechanical technique called chemically specific high-resolution
      force spectroscopy. The data taken on approach of the probe tip to the HA surface
      was compared to the nonlinear Poisson-Boltzmann-based electrostatic double layer
      theory to predict the surface charge per unit area of the HA, sigmaHA (C/m2), as
      a function of ionic strength, position within a variety of grains, and across
      grain boundaries. The average sigmaHA was found to be approximately -0.02 C/m2
      and to vary from -0.0037 to -0.072 C/m2 with nanoscale position in relation to
      grain boundaries and crystal planes up to -0.19 C/m2/microm. Positional
      measurement of nanoscale surface properties holds great promise in elucidating
      the molecular origins of physicochemical processes occurring at the biomaterial
      interface.

PMID- 15262470
TI  - The effect of biomimetic apatite structure on osteoblast viability,
      proliferation, and gene expression.
AB  - The conventional biomimetic apatite coating process can be accelerated by
      immersing substrates into concentrated simulated body fluid (5 x SBF) at 37
      degrees C to form an initial coating of apatite precursor spheres, and transform
      the precursors into plate-like apatite structures. Depending on processing
      parameters, different apatite structures can be created over the same substrate.
      The purpose of this study is to investigate the effects of the different apatite
      microenvironment on cell spreading, viability, proliferation, and gene
      expression. MC3T3-E1 preosteoblasts were cultured on five surfaces: conventional
      apatite (CA), precursor apatite spheres (PreA), large plate-like apatites (LgA),
      small plate-like apatites (SmA), and tissue culture grade polystyrene (TCPS).
      PreA induced significantly higher cell death during the first two weeks. TCPS
      supported more uniform spreading (1 day) and higher proliferation (2 weeks) than
      CA, LgA, and SmA. Apatites restricted spreading and promoted the extension of
      cellular projections along the textured surfaces under confocal microscopy
      observation. By 3 weeks, LgA induced highest expression of mature osteogenic
      markers osteocalcin (OCN) and bone sialoprotein (BSP) in both regular and
      osteogenic culture media based on quantitative real-time RT-PCR. The results of
      this study suggest differential cell responses to subtle changes in apatite
      microenvironment.

PMID- 15262471
TI  - Rapid fabrication of keratin-hydroxyapatite hybrid sponges toward osteoblast
      cultivation and differentiation.
AB  - Wool keratin sponges were reported to be useful scaffolds for long-term and high
      density cell cultivation (J. Biotechnol. 93 (2002) 165). The hybrid of the
      keratin sponges with calcium phosphate materials gave the additional function.
      Two rapid fabrication methods for calcium phosphate hybrid biomaterials were
      described. Firstly, the CaP-precipitated sponges were obtained by only the
      immersion of the carboxyl-sponges, chemically introduced with high amount of
      carboxyl groups on the sponges, in calcium and phosphate ions containing buffers
      such as PBS(+) for only 1-3 days. Neither sponge, introduced with amino or amido
      groups or non-treated, gave significant calcium phosphate precipitation. The
      carboxyl-sponges were mimics of matrix gamma-carboxyglutamic acid protein, which
      is responsible for osteoblast calcification. Secondly, the hydroxyapatite
      particle suspension was added onto carboxyl-sponges to fabricate trapped sponge.
      The trapped hydroxyapatite particles might interact with keratin protein of the
      sponge walls. Preliminary experiments measuring the expression of alkaline
      phosphatase, early osteoblast differentiation marker, suggested that both hybrid
      sponges, CaP-precipitated and trapped sponges, alter the differentiation pattern
      of preosteoblasts, MC3T3-E1.

PMID- 15262472
TI  - Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem
      cells in vitro.
AB  - Multipotent cell types are rapidly becoming key components in a variety of tissue
      engineering schemes, and mesenchymal stem cells (MSCs) are emerging as an
      important tool in bone tissue regeneration. Although several soluble signals
      influencing osteogenic differentiation of MSCs in vitro are well-characterized,
      relatively little is known about the influence of substrate signals. This study
      was aimed at elucidating the effects of a bone-like mineral (BLM), which is vital
      in the process of bone bonding to orthopedic implant materials, on the osteogenic
      differentiation of human MSCs in vitro. Growth of a BLM film (carbonate apatite,
      Ca/P = 1.55) on poly(lactide-co-glycolide) (PLG) substrates was achieved via
      surface hydrolysis and subsequent incubation in a modified simulated body fluid.
      The BLM film demonstrated significantly increased adsorption of fibronectin, and
      supported enhanced proliferation of human mesenchymal stem cells (hMSCs) relative
      to PLG substrates. In the absence of osteogenic supplements hMSCs did not display
      a high expression of osteogenic markers on BLM or PLG. In the presence of
      osteogenic supplements hMSCs exhibited greater expression of osteogenic markers
      on PLG substrates than on BLM substrates, as measured by alkaline phosphatase
      activity and osteocalcin production. Taken together, these data support the
      concept that substrate signals significantly influence MSC growth and
      differentiation, highlighting the importance of carrier material composition in
      stem cell-based tissue engineering schemes.

PMID- 15262473
TI  - Tissue engineering of bone: effects of mechanical strain on osteoblastic cells in
      type I collagen matrices.
AB  - The aim of the present study was to investigate the effect of cyclic uniaxial
      mechanical strain on a human osteoblastic precursor cell line (hFOB 1.19) in
      three-dimensional type I collagen matrices. Cell seeded collagen constructs were
      mechanically stretched by a daily application of cyclic uniaxial strain using a
      special motor-driven apparatus and compared to unstretched controls. Expression
      of genes involved in cell proliferation and osteoblastic differentiation as well
      as matrix production were investigated by analyzing the mRNA of histone H4, core
      binding factor 1, alkaline phosphatase, osteopontin, osteocalcin, and collagen
      type I (Col I) up to a cultivation period of 3 weeks using real-time PCR. Cyclic
      stretching of cell seeded Col I matrices at a magnitude occurring in healing bone
      increased cell proliferation and slightly elevated the expression of nearly all
      investigated genes over unstrained controls at various time points. It was
      concluded that mechanical load promotes the proliferation and differentiation of
      osteoblastic precursor cells in a Col I matrix and that the application of
      mechanical stimuli may have a beneficial effect on in vitro tissue formation.

PMID- 15262474
TI  - Implantation of bone marrow mononuclear cells using injectable fibrin matrix
      enhances neovascularization in infarcted myocardium.
AB  - Neovascularization may improve cardiac function and prevent further scar tissue
      formation in infarcted myocardium. A number of studies have demonstrated that
      bone marrow-derived cells have the potential to induce neovascularization in
      ischemic tissues. In this study, we hypothesized that implantation of bone marrow
      mononuclear cells (BMMNCs) using injectable fibrin matrix further enhances
      neovascularization in infarcted myocardium compared to BMMNC implantation without
      matrix. To test this hypothesis, infarction was induced in rat myocardium by
      cryoinjury. Three weeks later, rat BMMNCs were mixed with fibrin matrix and
      injected into the infarcted myocardium. Injection of either BMMNCs or medium
      alone into infarcted myocardium served as controls. Eight weeks after the
      treatments, histological analyses indicated that implantation of BMMNCs using
      fibrin matrix resulted in more extensive tissue regeneration in the infarcted
      myocardium compared to BMMNC implantation without matrix. Examination with
      fluorescence microscopy revealed that cells labeled with a fluorescent dye prior
      to implantation survived in the infarcted myocardium at 8 weeks of implantation.
      Importantly, implantation of BMMNCs using fibrin matrix resulted in much more
      extensive neovascularization in infarcted myocardium than BMMNC implantation
      without matrix. The microvessel density in infarcted myocardium was significantly
      higher (p < 0.05) when BMMNCs were implanted using fibrin matrix (350 +/- 22
      microvessels/mm2) compared to BMMNC implantation without matrix (262 +/- 13
      microvessels/mm2) and medium injection (76 +/- 9 microvessels/mm2). In addition,
      average internal diameter of microvessels was significantly larger (p < 0.05) in
      BMMNC implantation with fibrin matrix group (14.6 +/- 1.2 microm) than BMMNC
      implantation without matrix group (10.2 +/- 0.7 microm) and medium injection
      group (7.3 +/- 0.5 microm). These results suggest that fibrin matrix could serve
      as a cell implantation matrix that enhances neovascularization efficacy for
      myocardial infarction treatment.

PMID- 15262475
TI  - A review on calcium phosphate coatings produced using a sputtering process--an
      alternative to plasma spraying.
AB  - New promising techniques for depositing hydroxyapatite (HA) and calcium phosphate
      (CaP) coatings on medical devices are continuously being investigated. Given the
      vast number of experimental deposition process currently available, this review
      will focus only on CaP and/or HA coatings produced using the sputtering process.
      This review will discuss the characterization of sputtered CaP coatings before
      and after post-deposition treatments and tissue responses to some of the
      characterized coating surfaces. From the studies observed in the literature,
      current research on sputtered CaP coatings has shown some promises that may
      eliminate some of the problems associated with the plasma-spraying process. It
      has been generally accepted that sputtered HA and CaP coatings improve bone
      strength and initial osseointegration rate. However, optimal coating properties
      required to achieve maximal bone response are yet to be reported. As such, the
      use of well-characterized sputtered CaP and/or HA surfaces in the evaluation of
      biological responses should be well documented to avoid controversial results. In
      addition, future investigations of the sputtering process should include clinical
      trials, to continue the understanding of bone responses to coated-implant
      surfaces of different properties, and the possibility of coupling sputtered HA
      and CaP coatings with growth factors.

PMID- 15262476
TI  - Periodontal ligament and gingival fibroblast adhesion to dentin-like textured
      surfaces.
AB  - It is known that the (micro-) structure of a substrate surface is of major
      influence on the growth behaviour of adherent cells. In the current study, we
      aimed to produce a surface that exactly mimics the structure of natural dentin,
      and to describe the effect of this surface on the growth behaviour of primary
      periodontal ligament fibroblasts (PDLF) or gingival fibroblasts (GF). First, we
      used scanning electron microscopy (SEM) and morphometric techniques to analyse
      the porous dentin structure. Then, using a template made by photolithographic
      techniques, cell culture dishes with similar surface structure were made. On
      these dishes, and on smooth controls, primary PDLF and GF were seeded and assayed
      up to 14 days for proliferation, alkaline phosphatase (ALP) activity, and
      collagen content. Also, cell morphology was observed with SEM and transmission
      electron microscopy (TEM). Results showed that GF showed significantly less ALP
      activity than PDLF. Abundant collagen fibres were only formed by GF grown on the
      textured surfaces. SEM assessment showed equal spreading of both cell types on
      smooth and textured surfaces. TEM showed a preferential deposition of ECM
      material in the texture porosity. From our study we can conclude that dentin-like
      surfaces have no negative effect on either cell type, and could be used to
      enhance extracellular matrix deposition in GF formation. However, considerable
      differences were observed between primary cells from different animals.
      Therefore, final efficacy of the surfaces remains to be proven in implantation
      experiments.

PMID- 15262477
TI  - Improving warfarin therapy in children: anticoagulation clinics are just the
      beginning.

PMID- 15262478
TI  - Anticoagulation clinics for children achieve improved warfarin management.

PMID- 15262479
TI  - The impact of venous thrombosis on quality of life.
AB  - Quality of life (QOL) is increasingly seen as an important outcome in clinical
      care. Etiology, diagnosis, and management of venous thrombosis have been studied
      extensively, but only few studies have examined the impact of venous thrombosis
      on quality of life. The purpose of this study was to examine the impact of venous
      thrombosis on quality of life in a well-defined population of patients with
      venous thrombosis, by using both a generic and a disease-specific quality of life
      measure. A total of 45 patients from the thrombosis clinic of the University of
      Vermont in Burlington, VT, returned a mailed questionnaire including the Short
      Form 36 (SF-36) and a disease-specific venous thrombosis-quality of life (VT-QOL)
      questionnaire about the problems faced by patients with venous thrombosis. The
      sample consisted of 13 men (28.9%) and 32 women (71.1%). The mean age was 44.1
      years, with a range from 21 to 80 years. Compared with population norms of a
      general U.S. population that were adjusted for age and sex (N= 2463), venous
      thrombosis patients scored significantly lower (p < 0.05) on all subscales of the
      SF-36. Patients with the postthrombotic syndrome (PTS) appeared to have more
      impairment in their quality of life as measured by both the SF-36 and the disease
      specific questionnaire. All correlations between the SF-36 subscales and the
      subscales of the VT-QOL were significant, most of them on a p < 0.01 level. Given
      the impact of venous thrombosis and the postthrombotic syndrome on quality of
      life, assessment of QOL should be included in future studies on the outcome of
      venous thrombosis.

PMID- 15262480
TI  - Fibrinogen and high molecular weight fibrinogen during and after normal
      pregnancy.
AB  - INTRODUCTION: Pregnancy has recently been described as a generalized
      intravascular inflammatory response to the conceptus. Total fibrinogen
      concentrations increase during pregnancy. The percentage high molecular weight
      fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase
      during acute-phase conditions like inflammation. Therefore, we investigated
      whether the percentage high molecular weight fibrinogen increases during normal
      pregnancy. MATERIALS AND METHODS: Eighteen healthy nulliparous women with
      uncomplicated pregnancies with normal course and outcome participated in this
      study. Five blood samples were drawn from every woman in the gestational age
      periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks
      after delivery. Total fibrinogen concentrations were determined according to
      Clauss and the percentage high molecular weight fibrinogen was assessed by SDS
      electrophoresis and densitometry after isolation of fibrinogen by precipitation.
      One-way analysis of variance (ANOVA) was used to evaluate differences between
      gestational age periods and correlation coefficients were calculated by Pearson's
      method. RESULTS: Total fibrinogen concentrations increased with advancing
      gestational age and decreased after delivery. The percentage high molecular
      weight fibrinogen of the total fibrinogen remained unaltered during and after
      pregnancy. CONCLUSIONS: During normal pregnancy, there is an increase of total
      fibrinogen concentrations with advancing gestational age, without a rise in
      percentage high molecular weight fibrinogen. After delivery, the total fibrinogen
      returns to baseline concentrations.

PMID- 15262481
TI  - Effect of supplementation with folic acid throughout pregnancy on plasma
      homocysteine concentration.

PMID- 15262482
TI  - Effects of platelet release products on neutrophilic phagocytosis and complement
      receptors.
AB  - INTRODUCTION: Platelets enhance leukocytic phagocytosis via the action of ATP and
      ADP in platelet release products (PRPr). The present study was designed to
      clarify the type of complements and complement receptors that are involved in
      phagocytosis activation by PRPr, ATP and ADP. MATERIALS AND METHODS: Human
      peripheral blood was used as the source of neutrophils and platelets. The
      supernatant of the platelet suspension after simulation was used as PRPr. The
      effects of PRPr, ATP, ADP, and other substances on neutrophilic phagocytosis,
      rosette formation and expression of several antigens were investigated. For the
      markers of neutrophilic phagocytosis and rosette formation, IgM-sensitized sheep
      red blood cells (SRBC) were treated with diluted human serum (EAC) or purified
      complements (C1, C4, C2 and C3) (EAC3b) followed by C3 inactivation (EAC3bi). The
      expressions of CD11b, CD11c, CD18, and CD35 were evaluated using a flow
      cytometer. RESULTS: Neutrophilic phagocytosis of EAC and EAC3bi was enhanced by
      PRPr, ATP, and ADP, whereas this phagocytosis activation was abolished by
      antibodies against CD11b and CD18. Neutrophil rosette formation with EAC3bi was
      increased by ATP and ADP. Flow cytometry revealed that the expressions of CD11b
      and CD35 on neutrophils were increased by PRPr, but not by ATP and ADP. The
      component in PRPr, responsible for the increase in expressions of these antigens,
      could not be identified. CONCLUSION: PRPr increases the neutrophilic phagocytosis
      of complement-coated particles through the action of ATP and ADP by increasing
      the binding avidity with iC3b, but not the number of Mac-1 (CD11b/CD18).

PMID- 15262484
TI  - Annexin V inhibits lipopolysaccharide-induced procoagulant activity on human
      monocytes.

PMID- 15262483
TI  - The degree of red blood cell aggregation on peripheral blood glass slides
      corresponds to inter-erythrocyte cohesive forces in laminar flow.
AB  - OBJECTIVE: To determine the degree of correlation between red blood cell (RBC)
      aggregation on peripheral blood glass slides (PBGS) as determined by image
      analysis and the inter-erythrocytic cohesive forces as determined in a
      computerized cell flow properties analyzer (CFA). STUDY DESIGN: RBC aggregation
      was assessed using both systems simultaneously in healthy volunteers, obese
      patients and hypercholesterolemic individuals before and following LDL apheresis.
      RESULTS: A significant (r = 0.5, p < 0.001) correlation was noted between the
      flow-dependent average aggregate size (AAS) obtained in the CFA and the degree of
      RBC aggregation on peripheral blood glass slides. Moreover, the enhanced RBC
      aggregation on the slides was positively associated with the appearance of larger
      aggregates in the CFA (r = 0.5, p < 0.001) and inversely with the formation of
      smaller aggregates (r = -0.27, p < 0.04). A similar reduction in RBC aggregation
      following LDL apheresis was noted in both systems. CONCLUSIONS: The phenomenon of
      RBC aggregation on peripheral blood glass slides is governed by significant inter
      erythrocytic cohesive forces and is not a result of a mere coincidental
      superimposition of cells. The slide test offers a rapid and simple method of
      evaluating rheologically significant RBC aggregation, and may allow
      stratification of patients at risk for atherothrombosis.

PMID- 15262485
TI  - Standard measurement of clot-bound thrombin by using a chromogenic substrate for
      thrombin.
AB  - We have developed an in vitro protocol for the measurement of clot-bound
      thrombin. This protocol uses a chromogenic substrate for thrombin and a
      microtiter plate reader and is suitable for screening inhibitors for thrombin
      that are directed to clot-bound thrombin. Clots were obtained after
      recalcification of human plasma. For the measurement of clot-bound thrombin, we
      read the optical density (OD) at 405 nm on a spectrophotometer and compared the
      results to that obtained with a standard curve of human alpha thrombin. We
      stopped the amidolytic reaction at 10 min because the optical density was linear
      until 20 min under our experimental conditions. We suggest that clot-bound
      thrombin can be measured using a chromogenic substrate specific for thrombin
      under our experimental condition.

PMID- 15262486
TI  - Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle
      cell migration.
AB  - INTRODUCTION: We determined the role of smooth muscle cell (SMC)-derived
      plasminogen activator inhibitor-1 (PAI-1) in the flow-induced SMC migratory
      response. MATERIALS AND METHODS: Wild type (wt) or PAI-1 knockout SMC were
      cultured in the absence or presence of endothelial cells (EC) under static or
      pulsatile flow conditions in a perfused culture system. SMC migration was then
      assessed by Transwell assay. RESULTS: Pulsatile flow significantly increased SMC
      PAI-1 mRNA and protein levels, approximately 4- and 3-fold respectively (n = 4, p
      < 0.05). In the absence, but not in the presence of EC, pulsatile flow
      significantly increased ( approximately 2.4-fold) the migration of wt SMC when
      compared to wt SMC cultured under static conditions. PAI-1 -/-SMC migration was
      significantly increased under flow conditions as compared to wild-type controls
      (334 +/- 22% vs. 237 +/- 11%, n = 6, p < 0.05). This flow-induced migration was
      significantly attenuated, but not completely inhibited, when PAI-1 -/-SMC were
      cultured in the presence of EC (147 +/- 13%, n = 6, p < 0.05). The flow-induced
      PAI-1 -/-SMC migratory response was partially inhibited by an anti-urokinase
      plasminogen activator (uPA) antibody (#1189), and completely inhibited by both
      1189 and the matrix metalloproteinase (MMP) inhibitor BB3103. In parallel PAI-1 
      /-SMC cells, there was a greater flow-induced increase in proMMP-2 activity as
      compared to wild-type control cells. Moreover, under both static and flow
      conditions, tissue inhibitors of matrix metalloproteinases (TIMP)-2 activity was
      reduced in these PAI-1-deficient cells as compared to wild-type controls.
      CONCLUSIONS: These results suggest that SMC PAI-1 plays a role in limiting flow
      induced SMC migration and thus may be an important mechanism for controlling the
      process of vascular remodelling.

PMID- 15262487
TI  - Anti-beta 2-glycoprotein I antibodies do not increase TF activity by de
      encryption.

PMID- 15262488
TI  - Diagnostic utility of comparing fibrinogen Clauss and prothrombin time derived
      method.

PMID- 15262489
TI  - Nonspecific antiviral immunity by formalin-fixed Coxiella burnetii is enhanced in
      the absence of nitric oxide.
AB  - Mice treated with a single injection of formalin-fixed Coxiella burnetii showed a
      significant increase in resistance to vaccinia virus (VV) infection compared to
      untreated mice. C. burnetii stimulated dramatically high levels of nitric oxide
      (NO) in the serum of treated mice, suggesting that NO might play a role in
      resistance to virus infection. To test this hypothesis, the effect of C. burnetii
      treatment on VV replication was examined in NOS2-/- and wild-type mice. C.
      burnetii treatment inhibited VV replication in both the knockout and wild-type
      mice but the effect was significantly greater in the NOS2-/- mice. Experiments in
      IFNgamma receptor knockout mice indicated that the nonspecific antiviral immunity
      induced by C. burnetii was dependent on IFNgamma and not NO. In the absence of
      NO, indoleamine 2,3-dioxygenase (IDO) was increased in C. burnetii-treated mice
      and this may contribute to the accelerated virus clearance in NOS2-/- mice.

PMID- 15262490
TI  - Lipid-raft-dependent Coxsackievirus B4 internalization and rapid targeting to the
      Golgi.
AB  - Coxsackievirus B4 (CBV4), a member of the Picornavirus genus, has long been
      implicated in the development of insulin-dependent diabetes mellitus (IDDM), by
      viral-induced pancreatic cell damage. Although the pancreotropic nature of this
      virus is well documented, the early stages of CBV4 viral infection that involve
      the attachment of virions to the cell surface by binding to their cellular
      receptors followed by entry into the cell, are poorly understood. In this study,
      we show that the entry of CBV4 requires functional lipid rafts as the site of
      virus attack. In addition, we show that this virus is endocytosed independently
      of clathrin-associated machinery and is delivered to the Golgi via a lipid-raft
      dependent mechanism.

PMID- 15262491
TI  - The nonresponse to hepatitis B vaccination is associated with impaired lymphocyte
      activation.
AB  - Nonresponsiveness against hepatitis B vaccination has been described in 4-10% of
      immunized subjects. We have explored the specific cell response to hepatitis B
      surface antigen by analyzing: PBMC proliferation, cytokine production (Th1, Th2
      profiles, and TGF-beta), and activation molecules on Th cells. A poor
      proliferative response was demonstrated in nonresponders (P < 0.05). T cells from
      responders produced all tested cytokines (P < 0.01), in contrast with
      nonresponders subjects (P < 0.05). Expression of CD69 and CD25 was diminished in
      T cells from nonresponders (P < 0.01). A reduced expression of CD40L was also
      detected in T cells from nonresponders (P < 0.01). An elevated correlation
      coefficient was observed between CD40L on CD4+ cells and antibody production.
      These results suggest an overall inability of T cells to be activated which could
      be consistent with potential differences in antigen presentation. In conclusion,
      our results suggest that an altered Th response may be a consequence of
      inappropriate early activation events.

PMID- 15262492
TI  - Unique three-repeat sequences containing FVa, LVb/C4, and CORE motifs in LTR-U3
      of Friend murine leukemia virus clone A8 accelerate the induction of thymoma in
      rat.
AB  - Friend murine leukemia virus (Fr-MLV) clone A8 causes thymoma 7 weeks
      postinfection in rats with a more rapid progression than clone 57. The U3 region
      of A8-LTR contains a unique structure of enhancer motifs consisting of three
      repeats of a 38-bp sequence containing FVa, LVb/C4, and CORE motifs. Replacement
      or deletion of the 38-bp sequence in the A8-U3 resulted in a marked reduction in
      tumorigenicity. Furthermore, the virus with 57-U3 gained high tumorigenicity
      after construction of the three 38-bp repeats in the U3 region. These findings
      indicated that the repeats of the 38-bp sequence of A8-LTR are essential for the
      rapid induction of thymoma. Interestingly, the repeat of the 38-bp sequence did
      not accelerate the amount of integrated viral DNA in the thymus during the early
      phase of infection, although it contributed to higher production of infectious
      virus. Thus, it was demonstrated that the ability to induce thymoma, which
      correlates with virus titer in the thymus, is not determined by the rate of viral
      DNA integration into the host genome.

PMID- 15262493
TI  - A fragile lattice: replacing bacteriophage lambda's head stability gene D with
      the shp gene of phage 21 generates the Mg2+-dependent virus, lambda shp.
AB  - Phage lambda DNA packaging is accompanied by prohead expansion, due to structural
      changes in gpE, the major capsid protein. Rearrangement of the gpE lattice
      creates binding sites for trimers of gpD, the head stabilization protein. lambda
      Like phage 21's shp gene is homologous to lambda's D gene. gpD and gpShp share
      49% amino acid identity. To ask whether gpShp could stabilize the lambda head
      shell, we replaced lambda's D gene with shp, creating lambda shp. Unlike lambda
      or 21, lambda shp was strictly dependent on the presence of 10(-2) M Mg2+, and
      lambda shp virions were very sensitive to chelating agents. Density gradient
      studies indicated that the lambda gpE lattice was underpopulated with gpShp.
      gpD's N-terminus has been proposed to contact gpE, and we found that lambda
      D/shp, which produces a chimeric protein with the N-terminus of gpD and the C
      terminus of gpShp, was Mg2+-independent and more stable than lambda shp.

PMID- 15262494
TI  - Simian immunodeficiency virus Vpr/Vpx proteins kill bystander noninfected CD4+ T
      lymphocytes by induction of apoptosis.
AB  - The depletion of CD4+ T-lymphocytes central to the immunodeficiency in acquired
      immunodeficiency syndrome (AIDS) is largely mediated by apoptosis of both
      infected and uninfected cells, but the mechanisms involved and the viral proteins
      responsible are still poorly characterized. It has recently been suggested that,
      in human and simian immunodeficiency virus (HIV) and SIV, Vpr is a major
      modulator of apoptosis in infected cells. Recently, we have reported on a chimera
      of caprine arthritis-encephalitis virus (CAEV) carrying vpr/vpx genes from
      SIVmac239, which is replication competent in goat macrophages but not in
      lymphocytes or human cells. Despite infection being restricted to macrophages,
      inoculation of primary goat peripheral blood mononuclear cells (PBMCs) with this
      chimera induced apoptosis in the lymphocyte population. In addition, when
      infected goat synovial membrane (GSM) cells were co-cultured with human CD4+ T
      lymphocyte SupT1 cell line, these CD4+ T cells showed increased apoptosis. The
      parental CAEV induced no significant apoptosis in goat PBMC cultures or in co
      cultures with human SupT1 lymphocytes. This indicates that SIV Vpr/Vpx proteins
      indeed mediate apoptosis of T-lymphocytes and, moreover, do so without the need
      for active infection of these cells. Moreover, this apoptosis was observed when
      SupT1s were cocultured in direct contact, but not in absence of contact with CAEV
      pBSCAvpxvpr-infected GSM cells. In view of these data, we propose that SIV
      Vpx/Vpr activate cell-to-cell contact-dependent extracellular signaling pathways
      to promote apoptotic death of uninfected bystander T-lymphocytes. Understanding
      this mechanism might bring insight for intervening in the loss of CD4+ T
      lymphocytes in the SIV infection model and in human AIDS.

PMID- 15262495
TI  - Codon optimization of the human papillomavirus 11 (HPV 11) L1 gene leads to
      increased gene expression and formation of virus-like particles in mammalian
      epithelial cells.
AB  - The 505 amino acid L1 protein of the human papillomavirus type 11 (HPV 11) is the
      major capsid polypeptide that has been shown to self-assemble into virus-like
      particles (VLPs) in vivo and in vitro. While L1 is essential for viral infection,
      expression studies in mammalian cells have been hampered by different codon
      preference between the virus and its host. To optimize L1 gene expression in
      mammalian cells, we converted wild-type HPV 11 L1 (11 L1wt) codons to those more
      common in human genes. The modified HPV 11 L1 gene (11 L1h) generated protein
      levels that were at least 100-fold higher than those of wild-type HPV 11 L1,
      while no obvious differences were seen in the level of mRNA. HPV 11 L1 protein
      was detected in mammalian epithelial and fibroblast cells, by immunoblotting and
      indirect immunofluorescence (IIF) techniques. Unlike the situation in situ, IIF
      revealed the presence of L1 mainly at perinuclear sites. Virus-like particles
      assembled intranuclearly only to a low extent, as indicated by transmission
      electron microscopy. DNA vaccination using the HPV 11 L1h gene yielded a drastic
      increase in L1-specific antibody production in mice as compared to immunization
      with the wild-type gene.

PMID- 15262496
TI  - Characterization of the Herpesvirus saimiri Orf51 protein.
AB  - Herpesvirus saimiri (HVS) is a gamma(2)-herpesvirus sharing genomic colinearity
      and a high degree of functional homology with HHV-8. To begin exploring the
      correlates of HVS infectivity and neutralization, we designed and implemented a
      new reporter assay. Using this assay, we could demonstrate that HVS neutralizing
      antibodies are present at high levels in naturally infected squirrel monkeys and
      are strongly induced after pathogenic, experimental infection of common
      marmosets. Further, we demonstrated that viral entry is influenced by cellular
      glycosaminoglycans and that, similar to HHV-8, soluble heparin is capable of
      blocking infectivity. We next cloned and characterized the positional homologue
      of HHV-8 K8.1, HVS Orf51. N-glycosidase F treatment indicates that like K8.1,
      Orf51 is a glycoprotein. Found in the viral particle, it localizes to the
      endoplasmic reticulum of expressing cells. Like K8.1, Orf51 could bind to agarose
      conjugated heparin, implicating this molecule in viral attachment to cells. These
      studies provide the groundwork for additional experiments into the role that this
      protein may be playing in viral pathogenicity, persistence, and cell tropism.

PMID- 15262497
TI  - Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not
      only class I MHC but also CD1a, in immature dendritic cells.
AB  - The effects of Nef molecules on immature dendritic cells (iDCs) were analyzed
      using recombinant human immunodeficiency virus type 1 (HIV-1) with intact nef
      gene, pseudotyped with vesicular stomatitis virus glycoprotein, HIV/VSV-G/+Nef.
      When iDCs were infected with HIV/VSV-G/+Nef, the surface expression of CD1a, a
      molecule for presenting glycolipid/lipid antigens, was selectively down-regulated
      among CD1 molecules (CD1a, -b, -c, and -d) as well as class I MHC. Moreover, the
      CD1a molecules were also down-modulated and co-localized with DsRed2-tagged-Nef
      in CD1a-transfected cells. Their co-localization was dependent upon CD1a
      cytoplasmic tail and the CD1a was redistributed from cell surface to LAMP-1+ late
      endosomal/lysosomal compartment. These findings reveal that the HIV-1-Nef
      interferes with the intracellular trafficking of CD1a, and suggest the
      involvement of CD1a-restricted immune effectors in the protective immunity
      against HIV-1 infection, which implicates the feasibility of virus-derived
      glycolipid/lipid antigens together with epitope peptides for the vaccine
      development.

PMID- 15262498
TI  - Analysis of a viral replication repressor: sequence requirements for a large
      symmetrical internal loop.
AB  - Nearly all members of the Carmovirus genus contain a structurally conserved 3'
      proximal hairpin (H5) with a large internal symmetrical loop (LSL). H5 has been
      identified as a repressor of minus-strand synthesis in a satellite RNA (satC),
      which shares partial sequence similarity with its helper virus Turnip crinkle
      virus (TCV). Repression was due to sequestration of the 3' end mediated by base
      pairing between 3' end sequence and the 3' side of the LSL (G. Zhang, J. Zhang
      and A. E. Simon, J. Virol., in press). Single site mutational analysis and in
      vivo genetic selection (SELEX) of the 14 base satC H5 LSL indicated specific
      sequences in the middle and upper regions on both sides of the LSL are necessary
      for robust satC accumulation in plants and protoplasts. Fitness of wild-type satC
      and satC LSL mutants to accumulate in plants, however, did not necessarily
      correlate with the ability of these RNAs to replicate in protoplasts. This
      suggests that the LSL might be involved in processes in addition to repression of
      minus-strand synthesis.

PMID- 15262499
TI  - Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains
      bearing a dipeptide insertion in the fingers subdomain of the reverse
      transcriptase and mutations at codons 67 and 215.
AB  - A two-serine insertion at position 69 (i69SS) of human immunodeficiency virus
      type 1 (HIV-1) reverse transcriptase (RT) appears to be critical to enhance multi
      nucleoside RT inhibitor resistance (MNR) in the sequence context of multiple
      zidovudine (AZT) resistance mutations (i.e., M41L, L210W, T215Y). In this study,
      we measured the replication capacity relative to the wild-type (WT) HIV-1 of a
      series of recombinant viruses carrying the i69SS in the background of a clinical
      isolate with MNR in which we introduced mutations D67N, Y215T, Y215S, or Y215N.
      In vitro measurements included replication kinetics and growth competition assays
      at different multiplicities of infection (MOI). While the addition of D67N had a
      minor effect on replication capacity, the reversion of Tyr-215 to Thr, Ser, or
      Asn was sufficient to increase the virus ability to replicate in a drug-free
      environment. The same genotypic changes at position 215 rendered the MNR virus
      susceptible to AZT and stavudine. Interestingly, the presence of the insertion
      together with mutation T215Y in an otherwise WT sequence background was not
      sufficient to confer high-level resistance to AZT, although its replication
      capacity was clearly impaired. Therefore, the RT residue 215 plays a critical
      role in both replication capacity and drug resistance of multidrug-resistant
      viruses containing the i69SS.

PMID- 15262501
TI  - Andes virus M genome segment is not sufficient to confer the virulence associated
      with Andes virus in Syrian hamsters.
AB  - Sin Nombre virus (SNV) and Andes virus (ANDV), members of the genus Hantavirus,
      in the family Bunyaviridae, are causative agents of hantavirus pulmonary syndrome
      (HPS) in North and South America, respectively. Although ANDV causes a lethal HPS
      like disease in hamsters, SNV, and all other HPS-associated hantaviruses that
      have been tested, cause asymptomatic infections of laboratory animals, including
      hamsters. In an effort to understand the pathogenicity of ANDV in the hamster
      model, we generated ANDV/SNV reassortant viruses. Plaque isolation of viruses
      from cell cultures infected with both parental viruses yielded only one type of
      stable reassortant virus: large (L) and small (S) segments of SNV and M segment
      of ANDV. This virus, designated SAS reassortant virus, had in vitro growth and
      plaque morphology characteristics similar to those of ANDV. When injected into
      hamsters, the SAS reassortant virus was highly infectious and elicited high
      titer, ANDV-specific neutralizing antibodies; however, the virus did not cause
      HPS and was not lethal. These data indicate that the ANDV M genome segment is not
      sufficient to confer the lethal HPS phenotype associated with ANDV.

PMID- 15262500
TI  - Quantification of infectious HIV-1 plasma viral load using a boosted in vitro
      infection protocol.
AB  - Methods currently used for HIV-1 viral load measurements are very sensitive, but
      cannot distinguish between infectious and noninfectious particles. Here we
      describe the development of a novel, sensitive, and highly reproducible method
      that allows rapid isolation and quantification of infectious particles from
      patient plasma. By immobilizing HIV-1 particles in human plasma to platelets
      using polybrene, we observed a 10- to 1000-fold increase in infectivity over
      infection protocols using free virus particles. Using this method, we evaluated
      infectivity in plasma from 52 patients at various disease stages. At plasma viral
      loads of 1000-10000 HIV-1 RNA copies/ml 18%, at 10,000-50,000 copies/ml 73%, at
      50,000-100,000 copies/ml 90%, and above 100,000 copies 96% of cultures were
      positive. We found that infectious titers among patients vary distinctively but
      are characteristic for a patient over extended time periods. Furthermore, we
      demonstrate that by evaluating infectious titers in conjunction with total HIV
      RNA loads, subtle effects of treatment intervention on viremia levels can be
      detected. The immobilization procedure does not interfere with viral entry and
      does not restore the infectivity of neutralized virus. Therefore, this assay
      system can be utilized to investigate the influence of substances that
      specifically affect virion infectivity such as neutralizing antibodies, soluble
      CD4, or protease inhibitors. Measuring viral infectivity may thereby function as
      an additional, useful marker in monitoring disease progression and evaluating
      efficacy of antivirals in vivo.

PMID- 15262502
TI  - Development of a safe neutralization assay for SARS-CoV and characterization of S
      glycoprotein.
AB  - The etiological agent of severe acute respiratory syndrome (SARS) has been
      identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike
      (S)-glycoprotein of the virus interacts with a cellular receptor and mediates
      membrane fusion to allow viral entry into susceptible target cells. Accordingly,
      S-protein plays an important role in virus infection cycle and is the primary
      target of neutralizing antibodies. To begin to understand its biochemical and
      immunological properties, we expressed both full-length and ectodomain of the
      protein in various primate cells. Our results show that the protein has an
      electrophoretic mobility of about 160-170 kDa. The protein is glycosylated with
      high mannose and/or hybrid oligosaccharides, which account for approximately 30
      kDa of the apparent protein mass. The detection of S-protein by immunoassays was
      difficult using human convalescent sera, suggesting that the protein may not
      elicit strong humoral immune response in virus-infected patients. We were able to
      pseudotype murine leukemia virus particles with S-protein and produce SARS
      pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner
      and the infection could be specifically inhibited by convalescent sera.
      Consistent with low levels of antibodies against S-protein, neutralizing activity
      was weak with 50% neutralization titers ranging between 1:15 to 1:25. To
      facilitate quantifying pseudovirus-infected cells, which are stained blue with X
      Gal, we devised an automated procedure using an ELISPOT analyzer. The high
      throughput capacity of this procedure and the safety of using SARS pseudoviruses
      should make possible large-scale analyses of neutralizing antibody responses
      against SARS-CoV.

PMID- 15262504
TI  - The C-type lectin homologue gene (EP153R) of African swine fever virus inhibits
      apoptosis both in virus infection and in heterologous expression.
AB  - The open reading frame EP153R of African swine fever virus (ASFV) encodes a
      nonessential protein that has been involved in the hemadsorption process induced
      in virus-infected cells. By the use of a virus deletion mutant lacking the EP153R
      gene, we have detected, in several virus-sensitive cells, increased levels of
      caspase-3 and cell death as compared with those obtained after infection with the
      parental BA71V strain. Both transient and stable expression of the EP153R gene in
      Vero or COS cells resulted in a partial protection of the transfected lines from
      the apoptosis induced in response to virus infection or external stimuli. The
      presence of gene EP153R resulted in a reduction of the transactivating activity
      of the cellular protein p53 in Vero cell cultures in which apoptosis was induced
      by virus infection or staurosporine treatment. This is to our knowledge the first
      description of a viral C-type lectin with anti-apoptotic properties.

PMID- 15262503
TI  - Genetic diversity in chlorella viruses flanking kcv, a gene that encodes a
      potassium ion channel protein.
AB  - The chlorella virus PBCV-1 encodes a 94-amino acid protein named Kcv that
      produces a K+-selective and slightly voltage-sensitive conductance when expressed
      in heterologous systems. As reported herein, (i) Northern analysis of kcv
      expression in PBCV-1-infected cells revealed a complicated pattern suggesting
      that the gene might be transcribed as a di- or tri-cistronic mRNA both at early
      and late times after virus infection. (ii) The protein kinase inhibitors H-89,
      A3, and staurosporine inhibited PBCV-1 Kcv activity in Xenopus oocytes,
      suggesting that Kcv activity might be controlled by phosphorylation or
      dephosphorylation. (iii) The PBCV-1 genomic sequence revealed a gene encoding a
      putative protein kinase (pkx) adjacent to kcv. These findings prompted us to
      examine the kcv flanking regions in 16 additional chlorella viruses and
      transcription in two of these viruses, as well as the effect of the three protein
      kinase inhibitors on two Kcv homologs in Xenopus oocytes. The results indicate
      (i) pkx is always located 5' to kcv, but the spacing between the two genes varies
      from 31 to 1588 nucleotides. More variation occurs in the kcv 3' flanking region
      of the 16 viruses. (ii) The kcv gene is expressed as a late mono-cistronic mRNA.
      (iii) Unlike the affect on PBCV-1 Kcv, the three protein kinase inhibitors have
      little or no effect on the activity of the two Kcv homologs in oocytes. (iv) A
      comparison of the kcv 5' upstream sequences from the 16 viruses identified a
      highly conserved 10-nucleotide sequence that is present in the promoter region of
      all of the viruses.

PMID- 15262505
TI  - Identification of glycosylation sites in the SU component of the Avian
      Sarcoma/Leukosis virus Envelope Glycoprotein (Subgroup A) by mass spectrometry.
AB  - We used enzymatic digestion and mass spectrometry to identify the sites of
      glycosylation on the SU component of the Avian Sarcoma/Leukosis virus (ASLV)
      Envelope Glycoprotein (Subgroup A). The analysis was done with an SU(A)-rIgG
      fusion protein that binds the cognate receptor (Tva) specifically. PNGase F
      removed all the carbohydrate from the SU(A)-rIgG fusion. PNGase F is specific for
      N-linked carbohydrates; this shows that all the carbohydrate on SU(A) is N
      linked. There are 10 modified aspargines in SU(A) (N17, N59, N80, N97, N117,
      N196, N230, N246, N254, and N330). All conform to the consensus site for N-linked
      glycosylation NXS/T. There is one potential glycosylation site (N236) that is not
      modified. Removing most of the carbohydrate from the mature SU(A)-rIgG by PNGase
      F treatment greatly reduces the ability of the protein to bind Tva, suggesting
      that carbohydrate may play a direct role in receptor binding.

PMID- 15262506
TI  - The origin of phospholipids of the enveloped bacteriophage phi6.
AB  - The phospholipid class and molecular species compositions of bacteriophage phi6
      and its host Pseudomonas syringae were determined quantitatively using TLC and
      liquid-chromatography/electrospray ionization mass-spectrometry. In addition, the
      fatty acid compositions of the phospholipids were analyzed by gas
      chromatography/mass-spectrometry. The phage contained significantly more
      phosphatidylglycerol (PG) and less phosphatidylethanolamine (PE) than the host
      cytoplasmic (CM) and outer (OM) membranes. In addition, the phospholipid
      molecular species composition of the viral membrane differed from those of the
      host membranes, but resembled that of CM more than OM as shown by principal
      component analysis (PCA). The membrane of phi6 contained more 34:1 and 34:2, and
      less 32:1 PE and PG molecular species than the host CM or OM. Also, phi6
      contained negligible amounts of saturated phospholipid molecular species. These
      data provide the first biochemical evidence suggesting that phi6 obtains its
      lipids from the CM. This process is not unselective, but certain phospholipid
      species are preferentially incorporated in the phage membrane. Common factors
      leading to similar enrichment of PG in every membrane-containing bacterial virus
      system studied so far (phi6, PM2, PRD1, PR4, Bam35) are discussed.

PMID- 15262508
TI  - Recent trends becoming standard of care yielding smaller, more successful
      operations at a lower cost.
AB  - Surgeons are now performing much smaller, more directed parathyroid operations in
      less time, and reported cure rates are the highest they have ever been. The
      ability to operate physiologically,and not just anatomically, has allowed a more
      directed and confident approach. This approach has subsequently led to minimal
      use of anesthesia and to immediate postoperative discharge,changes that have been
      embraced enthusiastically by referring endocrinologists. This article discusses
      the intraoperative monitoring used by the author and the pitfalls that can await
      the inexperienced surgeon.

PMID- 15262507
TI  - Characterization of a baculovirus with a deletion of vlf-1.
AB  - Very late expression factor (VLF-1) of Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) is essential for high levels of expression of the
      very late genes p10 and polh, and evidence suggests VLF-1 may also be involved in
      viral DNA replication. In this study, investigations determined whether VLF-1 is
      essential for viral DNA replication by generating a vlf-1 knockout bacmid
      containing the AcMNPV genome through homologous recombination in Escherichia
      coli. Additionally, a vlf-1 repair bacmid was constructed by transposing the vlf
      1 ORF and native promoter region into the polh locus of the vlf-1 knockout
      bacmid. After transfecting these virus constructs into Spodoptera frugiperda (Sf
      9) cells, the vlf-1 knockout bacmid was unable to produce a viral infection while
      the repair bacmid propagated at wild-type levels. Experiments were performed to
      conclude whether the vlf-1 knockout phenotype was due to a defect in viral DNA
      synthesis or late gene transcription. Southern blot analyses determined that the
      vlf-1 knockout bacmid was able to replicate viral DNA but only to about one-third
      the level of wild-type or rescued controls. In addition, virion DNA was not
      detected in the supernatant of transfected cells, indicating that the DNA
      synthesized by the mutant virus was unable to assemble into virions that bud out
      of the cells. Analysis of viral gene transcription confirmed that late gene
      transcription was not affected by the vlf-1 knockout but transcription of the
      very late gene p10 was substantially reduced.

PMID- 15262509
TI  - Historical perspective of parathyroid disease.
AB  - This article highlights key historical developments in the understanding of
      parathyroid function and disease, a story that involves many clinical
      investigators and classic scientific debate. The current medical community is
      certainly indebted to the innate curiosity and perseverance of these historical
      figures.

PMID- 15262510
TI  - Primary, secondary, and tertiary hyperparathyroidism.
AB  - Primary, secondary, and tertiary hyperparathyroidism have evolved since their
      original description. What was once a debilitating disease has now become one
      with few symptoms on initial presentation. Complications from these disorders
      have decreased significantly because of earlier detection. Improved management of
      patients with chronic renal disease has also limited complications among those
      with secondary and tertiary hyperparathyroidism. Appropriate management is
      essential even in the early phase of the disorder to minimize the morbidities
      that may result if left untreated.

PMID- 15262511
TI  - Hyperparathyroidism and multiple endocrine neoplasia.
AB  - Multiple endocrine neoplasia (MEN) syndromes comprise the group of heritable
      endocrinopathies, MEN 1, MEN 2A, and MEN 2B. Primary hyperparathyroidism caused
      by multiglandular involvement is usually the initial manifestation in MEN 1,
      occurring in more than 90% of patients. In patients with MEN 2A,
      hyperparathyroidism develops less commonly and is usually milder than in MEN 1.
      Advances in genetics and molecular biology aid in confirming the diagnosis and
      screening relatives who are carriers or at risk for the disease. Surgery plays an
      important role in the management of hyperparathyroidism in both MEN 1 and MEN
      2A,although the timing and extent of surgery are areas of controversy.Long-term
      follow-up reveals a high rate of recurrent hyperparathyroidism in MEN 1 despite
      surgical intervention.

PMID- 15262512
TI  - An update from the latest workshop on asymptomatic primary hyperparathyroidism.
AB  - Considerable data have accumulated since 1990 concerning the natural history of
      asymptomatic primary hyperparathyroidism,the extent of target organ involvement,
      techniques for preoperative localization of parathyroid glands, and new surgical
      approaches for parathyroidectomy. Therefore a Workshop on Asymptomatic Primary
      Hyperparathyroidism: a Perspective for the Twenty-first Century was held in April
      2002 with a goal of reevaluating the conclusions from the 1990 National
      Institutes of Health (NIH)Consensus Development Conference. This article presents
      the recommendations of the workshop panel and discusses the evidence leading to
      the changes in the recommendations of the 1990 NIH conference.

PMID- 15262513
TI  - Significance of primary hyperparathyroidism in the management of osteoporosis.
AB  - Primary hyperparathyroidism (HPT) has catabolic effects on cortical bone and
      anabolic effects on cancellous bone with overall deleterious effects on skeleton.
      Primary HPT is associated with increased fracture risk both at the cancellous
      bone-enriched spine and the cortical bone-enriched distal one third of the
      radius. This risk is reversed by parathyroidectomy.

PMID- 15262514
TI  - Ultrasound examination of the parathyroid glands.
AB  - High-resolution sonography is a significant imaging tool available for evaluation
      of the parathyroid glands. It works particularly well in concert with nuclear
      imaging, especially in assisting preoperative localization of parathyroid lesions
      and in guiding interventional parathyroid procedures. Its limitations relate to
      anatomic areas not accessible to insonation. In the hands of an experienced
      examiner, it is a cost-efficient and important adjunct for the endocrine surgeon.

PMID- 15262515
TI  - Intraoperative rapid parathyroid hormone monitoring in parathyroid surgery.
AB  - The approach to parathyroid surgery has changed from bilateral exploration to
      focused, minimally invasive surgery. The intraoperative rapid parathyroid hormone
      assay has become an important tool in modern parathyroid surgery. This article
      outlines the technique and interpretation of the assay. Results of studies that
      evaluate the validity of the technique are summarized. The limitations and
      pitfalls of this technique are also discussed.

PMID- 15262516
TI  - Minimally invasive radioguided parathyroidectomy using intraoperative sestamibi
      localization.
AB  - This article presents the authors' technique of minimally invasive radio guided
      parathyroidectomy (MIRP) with intra-operative use of the hand-held gamma probe
      for primary HPT caused by a solitary adenoma. It points out how this approach
      varies from that of others who perform MIRP. It also illustrates ways to
      troubleshoot common problems with the technique in inexperienced hands. The goal
      is to present an understandable and systematic approach to MIRP for surgeons who
      do not currently use this technique. This article is not intended to replace
      formalized training, which is essential to master the technique.

PMID- 15262517
TI  - Unilateral and bilateral surgery for parathyroid disease.
AB  - The principles of successful parathyroid surgery, regardless of the approach,
      demand a clear understanding of the philosophy behind the surgical exploration. A
      systematic approach, founded in science and refined by experience, is necessary
      to achieve long-term, reproducible surgical success. This article discusses the
      underlying logic and the advantages and disadvantages of the two basic approaches
      to parathyroid pathology: unilateral and bilateral cervical exploration. The
      authors do not to advocate a particular technique;instead, they provide a
      conceptual framework to surgical parathyroid disease upon which more advanced
      discussion can be built.

PMID- 15262518
TI  - Molecular biology of primary hyperparathyroidism.
AB  - As molecular biology and genetic mapping receive wider application to human
      disease, genetic alterations have been identified with increased frequency in
      some patients with primary hyperparathyroidism(HPT). These alterations have been
      found in molecules related to cellular signaling and growth (RET proto
      oncogene)and in tumor suppressors that control cell cycle progression and gene
      transcription (cyclin D1 and the MEN1 gene product. Although primary HPT can
      usually be treated surgically without knowledge of which specific genetic
      alteration has occurred, this information may assist clinicians in identifying
      which patients will go on to develop multiglandular or recurrent disease. In
      addition,such an approach would facilitate more appropriate postoperative
      surveillance, as well as counseling and screening of family members who may be at
      high risk for HPT.

PMID- 15262520
TI  - Parathyroid carcinoma.
AB  - Parathyroid carcinoma is a relatively rare tumor that is prone to recurrence and
      poor loco-regional control. This article discusses the epidemiology,
      presentation, operative findings, pathology,management, genetics, outcome, and
      other aspects of parathyroid carcinoma.

PMID- 15262519
TI  - Parathyroid re-exploration.
AB  - Re-operative parathyroid surgery is always a challenge for the endocrine surgeon.
      This article discusses the issues the parathyroid surgeon must consider before
      and during re-operative surgery,with special attention to recently introduced
      adjunctive techniques.

PMID- 15262521
TI  - The cost-effectiveness of sestamibi scanning compared to bilateral neck
      exploration for the treatment of primary hyperparathyroidism.
AB  - This article presents a cost-effectiveness analysis to determine whether
      preoperative imaging with Tc99m-sestamibi for detection and treatment of solitary
      adenomas associated with primary hyperparathyroidism is cost-effective compared
      with routine bilateral neck exploration.

PMID- 15262522
TI  - Endoscopic parathyroidectomy.
AB  - This article describes the techniques of endoscopic and endoscopic assisted
      parathyroidectomy, with a special emphasis on the accumulated experience as well
      as the advantages and drawbacks of these novel techniques.

PMID- 15262523
TI  - Hypercalcemic hypocalciuria: a critical differential diagnosis for
      hyperparathyroidism.
AB  - A differential diagnosis for hyperparathyroidism includes all causes of
      hypercalcemia; the primary causes of which are primary hyperparathyroidism and
      humoral hypercalcemia of malignancy. Benign familial hypocalciuric hypercalcemia
      is a rare condition of primary importance because failure to recognize this
      entity leads to unnecessary surgery. There are a plethora of other rare causes of
      hypercalcemia that can be distinguished from primary hyperparathyroidism by
      history and laboratory profiles. This article discusses the main and less common
      causes of hypercalcemia and provides guidance for distinguishing among them.

PMID- 15262524
TI  - Prevention and management of complications in parathyroid surgery.
AB  - The most common complication of parathyroid surgery is operative failure.
      Recurrent laryngeal nerve paralysis, permanent hypoparathyroidism,hematoma, and
      error in diagnosis can also complicate initial parathyroid exploration. This
      article discusses specific ways to try to prevent these and other problems and
      gives detailed strategies to evaluate and manage affected patients.

PMID- 15262525
TI  - Nuclear medicine imaging of the parathyroid.
AB  - Nuclear medicine sestamibi parathyroid imaging is now a standard preoperative
      assessment for patients with hyperparathyroidism. Since the introduction of
      Technetium-99m (99mTc) sestamibi for parathyroid imaging in 1989 there has been a
      steady refinement in the imaging technique. The accuracy is determined by the
      scan technique employed, with the dual-isotope (123Iodine/99mTc sestamibi)scan
      providing better accuracy than the simpler sestamibi washout method. Now the
      pathologic parathyroid process can be localized preoperatively with great
      confidence, limiting the time and extent of the neck dissection and allowing a
      significant number of parathyroid surgeries to be performed as outpatient
      procedures.

PMID- 15262526
TI  - Calciphylaxis.
AB  - Calciphylaxis is a condition with a generally poor prognosis about which
      relatively little is known. Possible improvement in prognosis is noted if the
      diagnosis can be made early to avoid progression of soft tissue lesions and
      resulting complications. The mainstays of therapy are wound care and therapy
      aimed at controlling infection and the progression of disease. Parathyroidectomy
      seems to benefit some patients, but controversy remains as to the extent of
      overall patient benefit and scenarios for its appropriate use.

PMID- 15262528
TI  - Synthesis and anticonvulsant activity of some omega-(1H-imidazol-1-yl)-N
      phenylacetamide and propionamide derivatives.
AB  - In this study, eight new omega-(1H-imidazol-1-yl)-N-phenylacetamide and
      propionamide derivatives having 2,6-dimethyl, 2,6-dichloro, 2-chloro-6-methyl and
      2-isopropyl substitutions on N-phenyl ring were synthesized to evaluate
      anticonvulsant activity against maximal electroshock test. The most active
      compounds in the series were the derivatives bearing 2-isopropyl and 2,6-dimethyl
      substituents on N-phenyl ring.

PMID- 15262529
TI  - Diaryl-substituted salicyl- and anthranyl-ketoximes as potential estrogen
      receptor ligands.
AB  - 3,4-diphenylsalicylaldoxime and 3,4-diphenylanthranylaldoxime derivatives,
      containing small groups (methyl or ethyl) on the imine carbon atom, were
      synthesized and submitted to biological assays. Binding tests performed on
      uterine cytosol estrogen receptor (ER) preparation and on purified full-length
      human ERalpha and ERbeta, showed that the newly synthesised compounds exhibit
      considerably lower binding affinities with respect to reference non-substituted
      3,4-salicylaldoxime.

PMID- 15262530
TI  - 4-sulphamoylphenyl semicarbazones with anticonvulsant activity.
AB  - A series of 4-sulphamoylphenyl semicarbazone derivatives were prepared starting
      from sulphanilamide and screened for anticonvulsant activity. The results
      indicated that greater protection was obtained in the maximal electroshock screen
      (MES) and subcutaneous strychnine (scSTY) than the subcutaneous
      pentylenetetrazole (scPTZ) tests. All the compounds showed low neurotoxicity when
      compared to the clinically used drugs. Compounds with substituted acetophenone (8
      11) showed good activity in the rat oral MES screen. Seven compounds (6, 8-10,
      12, 14 and 15) exhibited anticonvulsant activity greater than sodium valproate.
      Among the new derivatives evaluated, compound 10 emerged as the most active
      compound as indicated by its protection in the MES and scSTY screens and with low
      neurotoxicity. Seven compounds possessed sedative-hypnotic activity.

PMID- 15262531
TI  - Antimycobacterial N-pyridinylsalicylamides, isosters of salicylamides.
AB  - The series of derivatives of substituted N-pyridinylsalicylamides were
      synthesized. The compounds were evaluated for in vitro antimycobacterial activity
      against Mycobacterium avium and two strains of Mycobacterium kansasii. In the
      quantitative structure activity relationships analysis (QSAR), the Free-Wilson
      and Hansch approaches were used but the analysis was not significant. (The
      standard deviations of regression coefficients were greater than the values of
      the coefficients). The molecules were separated the heterocyclic and salicyl
      moiety in the molecules, and the study of influences of substituents on salicyl
      moiety was used, as well. 5-chloro-pyridin-2-yl, and the substitution of the
      salicyl moiety by chlorine in position 4 or 5 had the strongest influence on the
      increase in antimycobacterial activity.

PMID- 15262532
TI  - Chemometric and derivative methods as flexible spectrophotometric approaches for
      dissolution and assaying tests in multicomponent tablets.
AB  - Two derivative spectrophotometric (ratio derivative spectra and algorithm
      bivariate calibration) and a chemometric methods (partial least squares, PLS) are
      proposed for the simultaneous determination of binary mixtures in tablet analysis
      and dissolutions tests, without prior separation. These approaches are
      successfully applied to quantify trimethoprim (TMP) combined with
      sulfamethoxazole (SMX) or sulfamethazine (SMZ) or sulfafurazole (SFZ) using the
      information in the absorption spectra of appropriate solutions. Beer's law was
      obeyed in the concentration range of 0.98-17.5 microg/ml for TMP, 0.95-17.2
      microg/ml for SMX, 1.16-17.5 microg/ml for SMZ and 0.97-17.4 microg/ml for SFZ.
      The first derivative (1D) bivariate algorithm method involves the use of four
      calibration curves: two for each compound at two different wavelengths, selected
      by Kaiser's method. Similarly, the first derivative ratio spectrophotometry
      employs the linear relationship between the ratio spectra of the analytes and the
      concentration range. The results were compared with those obtained by PLS
      multivariate calibration. The calibration models from PLS were pre-treated by
      orthogonal signal correction and evaluated by cross-validation using the 'SIMCA-P
      9' software. Synthetic mixtures of TMP and sulfonamides were used in five
      different sets for the validity of the calibrations. Mean recoveries for
      derivative ratio, derivative bivariate and PLS methods were found to be between
      99.7% and 102.0% for TMP, 99.4% and 100.2% for SMX, 99.3% and 101.0% for SMZ and
      98.1% and 102.3% for SFZ. The calibrations of the three methods were successfully
      applied to the assaying and dissolution of placebo and commercial tablets without
      any prior separation. More than 85% of TMP, SMX and SMZ were dissolved within 15
      min. For SFZ, only 85% of the compound was dissolved after 60 min. In this study,
      the three spectrophotometric methods can be satisfactorily used for the
      quantitative analysis and for dissolution tests of multicomponent dosage forms.

PMID- 15262533
TI  - Synthesis and antiproliferative activity of 3-aryl-2-[1H(2H)-benzotriazol-1(2)
      yl]acrylonitriles variously substituted: Part 4.
AB  - A new series of variously substituted 3-aryl-2-[1H(2H)-benzotriazol-1(2)
      yl]acrylonitriles was synthesized and tested for antiproliferative and
      antitubercular activity as part of our continuing research program in the
      antimicrobial and antitumor fields. The most cytotoxic derivatives (5a,g,i,j,l
      and 7b) (CC50 < 3.0 microM against MT-4 cells) were evaluated against a panel of
      human cell lines derived from hematological and solid tumors, using 6
      mercaptopurine (6-MP) and etoposide as reference drugs. In particular, E-2-(5,6
      dimethyl-1H-benzotriazol-1-yl)-3-(3-nitrophenyl)acrylonitrile (5g) resulted more
      potent than 6-MP on all cell lines, even if 2-14-fold less potent than etoposide.
      In the antitubercular screening, the derivatives 5i,j and 7e showed moderate
      activity against some resistant strains of Mycobacterium tested.

PMID- 15262534
TI  - Synthesis and cytotoxic evaluation of two novel anthraquinone derivatives.
AB  - The antitumor activity of dihydroxyanthracenediones such as mitoxantrone on a
      panel of cancer cell lines during the last 30 years, led investigators to
      synthesize thousands of anthracycline analogs and test their cytotoxicity to
      identify compounds superior to the parent drugs in terms of increased therapeutic
      effectiveness, reduced toxicity or both. To achieve this, new synthesized
      congeners either have different side arms or have extra rings on their skeletons.
      Following these studies, we proposed total synthesis of 2-amino-N-[4-(2-amino-3
      hydroxy-propionylamino)-9,10-dioxo-9,10-dihydroanthracene-1-yl]-3-hydroxy
      propionamide (V) and 6-amino-hexanoic acid [4-(5-amino-pentanoylamino)-9,10-dioxo
      9,10-dihydro-anthracen-1-yl]-amide (VI). Acetylation of 1,4-diaminobenzene using
      acetyl chloride and reaction with phthalic anhydride under a Friedel-Crafts
      reaction and then cyclization gave 1, 4-diamino-anthraquinone. This compound was
      reacted with two amino acids (L-serine and 6-amino hexanoic acid) in their ester
      forms, using ethyl chloroformate as a coupling agent. Hydrolyzing esterified
      compounds gave their amino substituted derivatives. These compounds with diamine
      side arms are supposed to provide better intercalation with DNA. Synthesized
      novel ametantrone derivatives were tested against a panel of cancer cells (KB,
      Hela, MDA-MB-468 and K562), using MTT assay. The results showed that tested
      compounds inhibited the growth of cancer cells at micromolar concentrations.
      However, compound (VI) was more cytotoxic than compound (V) probably because of
      its longer side chains and better intercalation with DNA.

PMID- 15262535
TI  - Cytotoxic-antineoplastic activity of acetyl derivatives of
      prenylnaphthohydroquinone.
AB  - Several acetyl derivatives of prenylnaphthohydroquinone have been synthetized and
      evaluated for their cytotoxicity against A-549 human lung carcinoma and H-116
      human colon carcinoma neoplastic cells. The IC50 values against A-549 are
      compared with those observed for previously reported unsubstituted derivatives.

PMID- 15262536
TI  - Electrophoretic properties of acrylic latex suspensions (Kollicoat MAE 30 D) and
      ibuprofen.
AB  - We have compared the electrophoretic properties (measured on the electrical
      surface) of the commercial latex Kollicoat MAE 30 D and the non-steroidal anti
      inflammatory drug (NSAID) ibuprofen in preparation for attempts to develop a
      suitable vehicle for the NSAID to obtain a modified release formulation.
      Electrophoretic mobility of the latex and the active principle was measured in
      solutions containing different concentrations of inorganic electrolytes (NaCl,
      CaCl2 and AlCl3) at different pH values. This was considered an indispensable
      first step for further characterization of the substance's electrical properties.
      Suspensions of both the latex and the drug had negative mobility values
      throughout the range of pH values studied here. Of the electrolytes, neither NaCl
      nor CaCl2 led to positive mobility, and no isoelectric point could be determined.
      However, AlCl3 at a concentration of 10(-3) M led to the greatest reduction in
      mobility. We therefore found that trivalent cations were more effective than
      divalent cations, which in turn were more effective than monovalent cations, in
      reducing mobility.

PMID- 15262537
TI  - Differential antiproliferative activity of new benzimidazole-4,7-diones.
AB  - Ten benzimidazole-4,7-diones were synthesized and tested in vitro on two tumor
      cell lines. Several compounds showed a significant antiproliferative activity on
      K562 cells, although to a different extent, whereas compound 1i showed a highly
      significant activity on SW620 cells, comparable to that of doxorubicin. Both the
      substituents in the quinone ring and the position of the nitrogen atom in the
      pyridine moiety play a crucial role for the biological activity.

PMID- 15262538
TI  - The cleavage of vitamin E galactoside in the rat tissue homogenates.
AB  - The stability of alpha-tocopheryl beta-galactoside in the presence of endogenous
      galactosidases in selected tissue homogenates (liver, kidney, ileum and brain)
      was estimated. High degree release of alpha-tocopherol from alpha-tocopheryl beta
      galactoside in tissues of ileum, kidney and brain was observed (82%, 75% and 72%,
      increase above endogenous alpha-tocopherol, respectively). A possible enzymatic
      mechanism of the galactoside decomposition was proposed.

PMID- 15262539
TI  - Breast cancer risk and possible screening strategies for young women following
      supradiaphragmatic irradiation for Hodgkin's disease.

PMID- 15262540
TI  - MRI of the marrow in the paediatric skeleton.
AB  - Magnetic resonance imaging (MRI) has greatly advanced evaluation of marrow
      diseases of the paediatric skeleton. As with many other aspects of paediatric
      radiology it is important to recognize the normal variations in the appearance of
      the marrow that occur in the growing child. These normal variations need to be
      differentiated from diseases and conditions that affect the marrow. This review
      describes the normal changes that occur in children with age, and the appearances
      of the pathological changes seen in infection, infiltration, haematological
      disorders, transplantation and radiation therapy.

PMID- 15262541
TI  - Magnetic resonance imaging of cartilage and cartilage repair.
AB  - Magnetic resonance (MR) imaging of articular cartilage has assumed increased
      importance because of the prevalence of cartilage injury and degeneration, as
      well as the development of new surgical and pharmacological techniques to treat
      damaged cartilage. This article will review relevant aspects of the structure and
      biochemistry of cartilage that are important for understanding MR imaging of
      cartilage, describe optimal MR pulse sequences for its evaluation, and review the
      role of experimental quantitative MR techniques. These MR aspects are applied to
      clinical scenarios, including traumatic chondral injury, osteoarthritis,
      inflammatory arthritis, and cartilage repair procedures.

PMID- 15262542
TI  - Multi-detector CT angiography of the intra-cranial circulation: normal anatomy
      and pathology with angiographic correlation.
AB  - Multidetector computed tomography angiography (MD-CTA) of the intra-cranial
      circulation shows great potential in the evaluation of intra-cranial vascular
      disease. Interpreting these studies requires a detailed knowledge of the
      technique, its advantages and disadvantages, as well as a strong understanding of
      normal intra-cranial vascular anatomy. The purpose of this review is to describe
      the technique for MD-CTA, demonstrate normal anatomy, anatomic variants and
      vascular pathology with an emphasis on aneurysms.

PMID- 15262543
TI  - Cardiac pacing systems and implantable cardiac defibrillators (ICDs): a
      radiological perspective of equipment, anatomy and complications.
AB  - Cardiac pacing is a proven and effective treatment in the management of many
      cardiac arrhythmias. Implantable cardiac defibrillators (ICDs) are beneficial for
      certain patient groups with a history of serious, recurrent ventricular
      dysrhythmias, with a high risk of sudden cardiac death. Pacemaker devices take
      many forms and are highly visible on the chest radiograph. The radiographic
      appearances of ICDs and pacemakers can be similar and are subject to similar
      complications. The anatomical approach to the implantation, the type of device
      used and anatomical variations will all affect the appearance of these devices on
      the chest film. Pacemaker complications identified radiographically include
      pneumothorax, lead malpositioning, lead displacement or fracture, fracture of
      outer conductor coil, loose connection between the lead and pacemaker connector
      block, lack of redundant loops in paediatric patients and excessive manipulation
      of the device by the patient (Twiddler's syndrome). This pictorial review
      highlights the role of chest radiography in the diagnosis of post-cardiac pacing
      and ICD insertion complications, as well as demonstrating the normal appearances
      of the most frequently implanted devices.

PMID- 15262544
TI  - Gastrointestinal and abdominal radiology.

PMID- 15262545
TI  - Semi-quantitative assessment of tricuspid regurgitation on contrast-enhanced
      multidetector CT.

PMID- 15262546
TI  - Semi-quantitative assessment of tricuspid regurgitation on contrast-enhanced
      multidetector CT.
AB  - AIM: To assess whether the early regurgitation of intravenous contrast medium
      into the inferior vena cava (IVC) and/or hepatic veins on computed tomography
      (CT), indicates tricuspid regurgitation (TR), and if so, whether it be used to
      grade severity. MATERIALS AND METHODS: We identified 86 consecutive patients that
      had been investigated for possible pulmonary endarterectomy at Papworth Hospital.
      From these, 61 patients were selected in whom CT, transthoracic echocardiography,
      and right heart catheterization (RHC) had been performed within 6 weeks. Using an
      arbitrary visual scale, the degree of TR assessed by intravenous contrast
      enhanced CT was compared with echocardiography. Results were analysed using a
      kappa weighted statistical test. In addition, CT and echocardiographic
      assessments of TR severity were correlated with pulmonary artery pressure
      measurements obtained by RHC (Spearman's rank correlation coefficient). RESULTS:
      CT assessment of TR had a sensitivity of 90.4% and a specificity of 100% in
      detecting echocardiographic TR. For TR graded as more than trivial by
      echocardiography, sensitivity of CT was 100%. With respect to RHC data, the
      correlation between severity assessment of TR between CT and echocardiography
      using the Kappa weighted coefficient was 0.56 (moderately good agreement). With
      respect to RHC data, the correlation between mean pulmonary pressure and TR
      grading on CT and echocardiography was r = 0.685 (p < 0.001) and r = 0.727 (p <
      0.001), respectively. CONCLUSION: Early opacification of the IVC or hepatic veins
      on first-pass contrast-enhanced CT almost invariably indicates TR. There is
      moderately good agreement between CT and echocardiographic assessment of the
      severity of TR. Both CT and echocardiographic grading of TR correlate well with
      RHC measurements of pulmonary artery pressure.

PMID- 15262547
TI  - Contrast enhancement of short T2 tissues using ultrashort TE (UTE) pulse
      sequences.
AB  - AIM: To review the effects of contrast administration on tissues with short T2s
      using a pulse ultrashort echo time (UTE) sequence. MATERIALS AND METHODS: Pulse
      sequences were implemented with echo times of 0.08 ms and three later gradient
      echoes. A fat-suppression option was used and later echo images were subtracted
      from the first echo image. Contrast enhancement with gadodiamide (0.3 mmol/kg)
      was used for serial studies in a volunteer. The images of 10 patients were
      reviewed for evidence of contrast enhancement in short T2 tissues. RESULTS:
      Contrast enhancement was seen in normal meninges, falx, tendons, ligaments,
      menisci, periosteum and cortical bone. In addition more extensive enhancement
      than with conventional pulse sequences was seen in meningeal disease,
      intervertebral disc disease, periligamentous scar tissue and periosteum after
      fracture. Subtraction of an image taken with a longer TE from the first image was
      of value in differentiating enhancement in short T2 tissues from that in long T2
      tissues or blood. CONCLUSION: Contrast enhancement can be identified in tissues
      with short T2s using UTE pulse sequences in health and disease.

PMID- 15262548
TI  - Magnetic resonance imaging of the Achilles tendon using ultrashort TE (UTE) pulse
      sequences.
AB  - AIM: To assess the potential value of imaging the Achilles tendon with ultrashort
      echo time (UTE) pulse sequences. MATERIALS AND METHODS: Four normal controls and
      four patients with chronic Achilles tendinopathy were examined in the sagittal
      and transverse planes. Three of the patients were examined before and after
      intravenous gadodiamide. RESULTS: The fascicular pattern was clearly demonstrated
      within the tendon and detail of the three distinct fibrocartilaginous components
      of an "enthesis organ" was well seen. T2* measurements showed two short T2*
      components. Increase in long T2 components with reduction in short T2 components
      was seen in tendinopathy. Contrast enhancement was much more extensive than with
      conventional sequences in two cases of tendinopathy but in a third case, there
      was a region of reduced enhancement. CONCLUSION: UTE pulse sequences provide
      anatomical detail not apparent with conventional sequences, demonstrate
      differences in T2* and show patterns of both increased and decreased enhancement
      in tendinopathy.

PMID- 15262549
TI  - A comparison of sonourethrography and retrograde urethrography in evaluation of
      anterior urethral strictures.
AB  - AIM: This prospective study was undertaken to evaluate the abnormalities of the
      male anterior urethra using high-resolution ultrasound (sonourethrography) and to
      compare the efficacy with that of retrograde urethrography (RGU) using operative
      findings as the gold standard. MATERIALS AND METHODS: Seventy patients with
      symptoms of lower urinary tract obstruction underwent RGU followed by
      sonourethrography. The sonologist was blinded to the findings of RGU. The
      parameters studied were compared with the intra-operative findings as gold
      standard, and the sensitivity, specificity and overall accuracy for the
      procedures were calculated. Chi-square test and kappa statistics were used where
      appropriate. RESULTS: All patients found to have urethral stricture disease by
      RGU were also detected by sonourethrography and confirmed intra-operatively. In
      the estimation of stricture length, RGU showed a lower sensitivity (60-80%) for
      lengths 1-4 cm, compared with sonourethrography (73.3-100%). Spongiofibrosis was
      detected by sonourethrography with a sensitivity of 77.3-83.3%. All the false
      tracts and calculi detected at sonourethrography were confirmed at surgery,
      whereas RGU showed a low sensitivity in their detection. The complications
      encountered during the procedures were pain, urethral bleeding and contrast
      intravasation. The frequency of pain during RGU was greater (p < 0.001); however,
      the difference in frequency of bleeding after the two procedures was not
      significant (p < 0.5). CONCLUSION: RGU and sonourethrography are equally
      efficacious in detection of anterior urethral strictures. Further
      characterization of strictures in terms of length, diameter and periurethral
      pathologies, like spongiofibrosis and false tracts, is done with greater
      sensitivity using sonourethrography as compared with RGU, with the added benefit
      of lower incidence of complications.

PMID- 15262550
TI  - Inter-observer variation in the interpretation of chest radiographs for pneumonia
      in community-acquired lower respiratory tract infections.
AB  - AIM: To assess inter-observer variation in the interpretation of chest
      radiographs of individuals with pneumonia versus those without pneumonia.
      MATERIALS AND METHODS: Chest radiographs of out-patients with a lower respiratory
      tract infection (LRTI) were assessed for the presence of infiltrates by
      radiologists from three local hospitals and were reassessed by one university
      hospital radiologist. Various measures of inter-observer agreement were
      calculated. RESULTS: The observed proportional agreement was 218 in 243 patients
      (89.7%). Kappa was 0.53 (moderate agreement) with a 95% confidence interval of
      0.37 to 0.69. The observed positive agreement (59%) was much lower than for
      negative agreement (94%). Kappa was considerably lower, if chronic obstructive
      pulmonary disease was present (kappa = 0.20) or Streptococcus pneumoniae (kappa =
      -0.29) was the infective agent. CONCLUSION: The overall inter-observer agreement
      adjusted for chance was moderate. Inter-observer agreement in cases with
      pneumonia was much worse than the agreement in negative (i.e. non-pneumonia)
      cases. A general practitioner's selection of patients with a higher chance of
      having pneumonia for chest radiography would thus not improve the observer
      agreement.

PMID- 15262551
TI  - MRI appearances of multiple rice body formation in chronic subacromial and
      subdeltoid bursitis, in association with synovial chondromatosis.

PMID- 15262552
TI  - Gastric lymphoid hyperplasia: radiological evidence of childhood Helicobacter
      pylori infection.

PMID- 15262553
TI  - Observer variation in the detection of colorectal neoplasia on double-contrast
      barium enema: implications for colorectal cancer screening and training.

PMID- 15262555
TI  - Occlusion of duodenocutaneous fistulae.

PMID- 15262557
TI  - Differential diagnosis of intra-cranial lesions with high signal on T1 or low
      signal on T2-weighted MRI.

PMID- 15262559
TI  - Major complications after percutaneous nephrostomy-lessons from a department
      audit.

PMID- 15262560
TI  - HIV/AIDS in Asia: introduction.

PMID- 15262561
TI  - The HIV/AIDS epidemic in China: history, current strategies and future
      challenges.
AB  - This article reviews the epidemic of HIV infection and AIDS, the Chinese national
      policy development in response to the epidemic, and disparities between policies
      and the need for AIDS prevention in China. The HIV epidemic in China has gone
      through three phases, and it is now at the rapid expansion phase. Since 1988,
      HIV/AIDS has been addressed from a legal perspective, but in the early stages
      laws and regulations actually hindered HIV control efforts. Since 1995 efforts
      have been made to improve policy decisions. Two major strategic plans were issued
      in 1998 and 2001, with increased government funding for implementation. Although
      the challenges facing HIV/AIDs control in China are many, the Chinese government
      is making a stronger commitment for implementing effective AIDS control measures
      in the country.

PMID- 15262562
TI  - Can the low HIV prevalence in Hong Kong be maintained?
AB  - Hong Kong is an area with low HIV prevalence. Public health services provided
      through the methadone clinics and public sexually transmitted diseases clinics
      have contributed to the control of HIV in Hong Kong. Nevertheless, surveillance
      indicates that HIV infections are increasing, especially in young male Chinese.
      The seropositivity rate of HIV in injection drug users is also increasing. A
      significant number of sexually transmitted infections, including syphilis and
      gonorrhoea, continue to occur. Continuing vigilance is required to prevent an
      increase in HIV infections.

PMID- 15262563
TI  - HIV/AIDS surveillance and prevention studies in Japan: summary and
      recommendations.
AB  - Japan is considered to have a low prevalence of HIV/AIDS, with a cumulative
      number of 2,556 AIDS cases and 5,140 HIV cases reported by the end of 2002.
      However, the recent trend of HIV cases shows a substantial increase, particularly
      among men who have sex with men and youth/young adults. The epidemiology of
      HIV/AIDS cases in Japan and a summary of current HIV prevention studies are
      presented based on surveillance data, research papers, and the Japanese
      government's annual reports on HIV behavioral and intervention studies of MSM,
      youths, and Japanese nationals who visit or are temporarily staying in the United
      States or Thailand. Recommendations and suggestions are presented for future HIV
      prevention research and structural changes in the Japanese government system,
      which funds HIV/AIDS care and prevention studies.

PMID- 15262564
TI  - HIV/AIDS in the Philippines.
AB  - HIV/AIDS has not yet caused a widespread epidemic in the Philippines. Rates in
      all the usual risk groups (sex workers, men who have sex with men, STD clients,
      returning overseas workers, etc.) have remained below 1%, except in a few areas,
      where they are still only 1-2% in some risk groups. The low level of HIV may be
      due in part to the low number of sex worker clients per night, the relatively low
      number of full-time sex workers, the low proportion of injectors among drug
      users, the early multisectoral response to the epidemic, and the presence of
      social hygiene clinics for sex workers. The incidence of STDs, multiple partners,
      and injection drug use with needle sharing, however, is increasing, suggesting
      that an explosive epidemic could occur if the virus is introduced into the
      appropriate risk groups. The Philippine government has confronted the problem of
      HIV/AIDS aggressively with an action plan that includes an emphasis on the
      response of the local government agencies, involvement and support of
      nongovernmental organizations (NGOs), incorporation of HIV/AIDS education into
      the school curriculum, and laws forbidding discrimination against persons with
      HIV/AIDS or belonging to risk groups. Local and international NGOs have been
      actively involved in prevention of HIV/AIDS and support of affected individuals.
      Although the Philippines is currently experiencing low rates of HIV/AIDS, the
      country needs to be prepared for the possibility of an explosive increase in the
      spread of HIV/AIDS. Vietnam and Indonesia provide examples of delayed epidemics
      of HIV/AIDS that could also occur in the Philippines.

PMID- 15262565
TI  - Update and projection on HIV/AIDS in Taiwan.
AB  - The HIV/AIDS epidemic in Taiwan started in 1986, with 5,221 cases of HIV
      infections, 1,596 cases of AIDS, and 911 deaths reported through 2003. National
      surveillance data indicate that men who have sex with men accounted for 48.2% of
      HIV infections, followed by heterosexual men (33.8%) and heterosexual women
      (6.1%). Only 353 (6.8%) of all HIV cases are females. The average age of HIV
      infected persons, AIDS cases, and deaths was 31.2, 36.2, and 39.0 years,
      respectively. The incidence of HIV infection has increased by approximately 15%
      every year since 1997. The continuing epidemic will likely burden the national
      health care system and may result in an estimated socioeconomic loss of U.S.
      dollars 1.6 billion in 2010, as 15,125 HIV infections and 1,420 deaths from AIDS
      are projected. To respond to the HIV/AIDS epidemic in Taiwan, the government has
      been working with nongovernmental organizations to promote HIV testing, conduct
      various education programs, and reach out to high-risk groups. HIV/AIDS patients
      are linked to medical care and provided with free highly active antiretroviral
      treatment. The main challenge is to reduce HIV-related stigma. Prevention focused
      on preventing further transmission of HIV by seropositive persons to others is
      urgently needed in fighting the HIV/AIDS epidemic.

PMID- 15262566
TI  - Current HIV/AIDS/STI epidemic: intervention programs in Cambodia, 1993-2003.
AB  - In the past decade, Cambodia has been experiencing the most serious HIV/AIDS
      epidemic in Southeast Asia. With full support from the top policy makers, good
      leadership in program management, and the commitment of the public health program
      officers, the HIV/AIDS prevention and care program in Cambodia has been
      successful, despite its resource constraints. Available data from surveillance
      and other studies in Cambodia indicate a downward trend in HIV prevalence and
      incidence among high-risk groups, an increase in condom use among commercial sex
      workers and their clients, and a declining trend of sexually transmitted
      infections. Although these findings reflect the success of programs to prevent
      transmission, the incidence of HIV infections is still high in high-risk
      populations, and transmission among the general population continues. Cambodia
      therefore needs to increase its efforts to reduce transmission. More research and
      prevention programs should focus on the vulnerable populations. HIV/AIDS modeling
      indicates that Cambodia needs to prepare for increasingly large numbers of AIDS
      patients who will require expensive medical care.

PMID- 15262567
TI  - The current situation of the HIV/AIDS epidemic in Indonesia.
AB  - Until 1999 the known prevalence of HIV in Indonesia was low, except for isolated
      geographic groups exposed to Thai fisherman. Since then, the prevalence among
      injection drug users in rehabilitation centers in Jakarta has risen rapidly to
      approximately 45-48%, according to surveys in 2001. By 2002 the prevalence had
      risen to 8-17% among female sex workers, 22% among transvestite sex workers, and
      4% among other male sex workers. Condom use is low in all groups, and there is
      considerable sexual mixing between risk groups. Surveys suggest that an
      increasing proportion of adolescents use drugs and have had sexual intercourse.
      Thus, although the epidemic in Indonesia is currently in the World Health
      Organization-defined "concentrated stage," all the ingredients for rapid spread
      are present. Intensive effective intervention strategies--condom use and clean
      needle use promotions--need to be implemented, especially in the high-risk
      groups, if a more serious epidemic is to be averted.

PMID- 15262568
TI  - The HIV/AIDS/STI situation in Lao People's Democratic Republic.
AB  - Lao People's Democratic Republic (Lao PDR) is a landlocked country with a
      population of 5.5 million and a total land area of 236,800 square kilometers. It
      has a population density of 23.3. It borders Thailand, Myanmar, China, Vietnam,
      and Cambodia. Its population distribution is 54.9% below the age of 20 years, and
      27.8% aged between 20 and 39 years (NSC, 2002). Women comprise 49.5% of the
      overall population. 1 National Statistics Center, Basic Statics, 2002; National
      Statics Center, Population Census.

PMID- 15262569
TI  - The HIV/AIDS epidemic country paper: Malaysia.
AB  - Since the first case of HIV/AIDS was identified in 1986 in Malaysia, the number
      of infected individuals has increased steadily each year, so that by the end of
      2002 the cumulative number of people living with HIV/AIDS was 57,835 (51,256 with
      HIV and 6,579 with AIDS), with 5,676 AIDS deaths. The epidemic in Malaysia,
      currently in a concentrated epidemic stage, is primarily fueled by drug use, but
      there is ample evidence that heterosexual transmission has increased over the
      last few years. A strategic plan that includes prevention, care, support, and
      treatment run by both the government and nongovernmental organizations has been
      in place since the beginning of the epidemic. However, Malaysia will need to take
      a more pragmatic approach to reduce new infections (which numbered 19 each day in
      2002) among the youth on whom the country relies for development. Leaders need to
      recognize that HIV/AIDS is not just a health issue, but also a socioeconomic
      concern that can eliminate all the developmental gains achieved over the years.
      Working together, Malaysians can overcome the epidemic, but there is a need to
      act quickly and to act in effective ways so that the devastating effects (already
      evident in the number of AIDS orphans and widows) can be reduced.

PMID- 15262570
TI  - HIV in Singapore--past, present, and future.
AB  - The first case of HIV infection in Singapore was reported in 1985. Between 1991
      and 1998, the number of reported cases of HIV and AIDS increased rapidly before
      stabilizing from 1999. The epidemiology of the AIDS epidemic in Singapore is
      characterized by a predominance of male cases (seven to one) and heterosexual
      transmission. A multipronged control program comprising public education and
      education of high-risk groups, legislation, protection of the national blood
      supply, management of cases, and epidemiological surveillance has been put in
      place. The promotion of condom use among local sex workers has been fairly
      successful, with very low rates of HIV and other sexually transmitted infections
      (STIs). However, freelance and potential indirect sex workers such as masseuses
      and lounge hostesses are a concern in view of their higher prevalence of HIV and
      STIs. Another concern is the high proportion of cases who are diagnosed only when
      they develop AIDS. A better understanding of sexual networks among men who have
      sex with men will enable more effective intervention programs for this group.
      Fresh innovative approaches are needed to encourage safe sex practices and early
      screening.

PMID- 15262571
TI  - Thailand's response to the HIV epidemic: yesterday, today, and tomorrow.
AB  - Thailand's comprehensive national response to the HIV/AIDS epidemic has been
      extensively documented since the beginning of epidemic. Substantial progress in
      the fight against HIV/AIDS has been made because awareness of the problem was
      raised. Top-level political commitment and multisectoral strategies mobilized
      funds and human resources to implement the control program at all levels.
      Behavioral change resulting in increased condom use in brothels on a national
      scale rose from virtually nil to more than 95%. This was accompanied by a 90%
      reduction of the sexually transmitted disease rate. In parallel, the rate of new
      HIV infections dropped by 80%. Despite these achievements, there remains an
      urgent need to continue efforts to ensure universal and unfailing condom use.
      Further, Thailand needs to establish pragmatic innovative approaches to reduce
      transmission, especially among injection drug users, women, and youth, as well as
      to develop effective strategies for implementation of antiretroviral treatment.
      Further strategies also need to consider the changing cultural, social, and
      economic characteristics of the Thai populations.

PMID- 15262572
TI  - HIV/AIDS epidemics in Vietnam: evolution and responses.
AB  - The goal of this study was to describe the evolution of the HIV epidemic in
      Vietnam and its responses. Surveillance was conducted in 8 provinces in 1994,
      expanded to 12 in 1995, 20 in 1996, and 30 in 2001. Sentinel populations were
      sexually transmitted disease (STD) patients, female sex workers (FSWs), injection
      drug users (IDUs), tuberculosis (TB) patients, antenatal women, and military
      conscripts. Vietnam is in the concentrated epidemic stage. HIV prevalence had
      increased significantly in all surveillance population groups in the 1990s. HIV
      prevalence in the south is higher than in other regions of the country. The
      national HIV prevalence increased from 10.1% in 1996 to 32% in 2002 among IDUs,
      from 0.6% in 1994 to 6.6% in 2002 among FSWs, from 0.4% in 1994 to 2.4% in 2002
      among STD patients, from 0.03% in 1994 to 0.34% in 2002 among pregnant women,
      from 0% in 1994 to 0.7% in 2002 among army military recruits, and from 0.5% in
      1994 to 3.6% in 2002 among TB patients. The government has a strong commitment to
      control the epidemic and has implemented many activities for HIV prevention and
      control. Vietnam's HIV epidemic is predominantly among IDUs. Current intervention
      activities have not been sufficient to reduce HIV transmission. Vietnam needs to
      strengthen responses by scaling up the best practices in the most affected
      population groups by implementing internationally recognised effective
      interventions appropriately.

PMID- 15262573
TI  - A review of the HIV epidemic in India.
AB  - India has a population of more than 1 billion people. Although only about 0.7% of
      its population is infected with HIV, it has more cases than any other country in
      the world, with more than 4.5 million HIV-seropositive patients. The epidemic of
      HIV/AIDS in India is distributed between the urban and rural populations mainly
      in the southern and western states of the country (APAC-VHS, Community Prevalence
      of Sexually Transmitted Diseases in Tamil Nadu-A Report, 1998; Solomon,
      Kumarasamy, Ganesh, & Amalraj, 1998, International Journal of Medical Research,
      85; 335-338). India has several different epidemics in various parts of the
      country. The epidemic in the western and southern states is primarily
      heterosexual. The northeastern states of India, being in geographical proximity
      to the Golden Triangle of Asia, initially experienced HIV in the injection drug
      user population and their sexual partners, but spread to the heterosexual
      population has been increasing. At present, the northern states, which are the
      most densely populated, appear to remain largely unaffected by the HIV epidemic.
      India has mounted a broad intervention program, including the government, and
      international, nongovernmental, and community-based organizations. The main
      barriers to effective control are insufficient resources, illiteracy, and stigma.
      Antiretroviral drugs are manufactured in the country and exported elsewhere, but
      their affordability (despite a drastic reduction in costs) and the feasibility of
      monitoring patients on drugs are in question. Starting April 1, 2004, the
      government of India has announced free provision of ART drugs to all who need it
      in the six most prevalent states of India.

PMID- 15262574
TI  - HIV/AIDS education and prevention in Myanmar.
AB  - Myanmar has a diverse population, 70% of whom reside in rural areas. These
      factors, along with limited resources, create a challenge for monitoring and
      controlling the HIV/AIDS epidemic. The first HIV-infected individual was
      identified in 1988, and the first AIDS case was reported in 1991. The National
      AIDS Control Program and the National AIDS Committee were established in 1989.
      Sentinel surveillance was begun in 1992. A cumulative total of 45,968 HIV/AIDS
      cases have been reported through 2003. UNAIDS and the government of Myanmar
      estimated that there were 177,279 persons living with HIV/AIDS in Myanmar in
      December 2001. High prevalence rates of HIV have been identified in injection
      drug users (IDUs), commercial sex workers (CSWs), and men attending sexually
      transmited disease clinics. Levels of HIV in all groups appear to have leveled
      off, but the prevalence remains high in IDUs and CSWs. A 100% targetted condom
      promotion program was implemented in 2001. Political commitment to control
      HIV/AIDS has been established through the leadership of the government and
      establishment of AIDS committees extending down to the township and rural health
      center levels. An increased understanding of the problems that Myanmar faces in
      controlling HIV transmission and increased support from international agencies
      and nongovernmental organizations can play an important role in facilitating more
      intensive intervention activities.

PMID- 15262577
TI  - New roles for mental and behavioral health experts to enhance emergency
      preparedness and response readiness.

PMID- 15262576
TI  - A national longitudinal study of the psychological consequences of the September
      11, 2001 terrorist attacks: reactions, impairment, and help-seeking.
AB  - This article examines the evolution of psychological and behavioral reactions
      following the September 2001 terrorist attacks in a nationally representative
      sample, and describes where people turned for support, information, and
      counseling. From November 9 to November 28, 2001, we resurveyed 395 (71%) of the
      original 560 adults 19 years or older within the United States who participated
      in our national random-digit-dialing telephone survey conducted on September 14
      to September 16, 2001, about their terrorism-related psychological distress and
      behavior. Sixteen percent of adults had persistent distress, reporting one or
      more substantial distress symptoms in both September and November. Adults with
      persistent distress reported accomplishing less at work (65%); avoiding public
      gathering places (24%); and using alcohol, medications, or other drugs to relax,
      sleep, or feel better because of worries about terrorism (38%). Seventy-five
      percent talked with family and friends; however, 43% reported sometimes feeling
      unable to share their terrorism-related thoughts and feelings with others because
      it made others uncomfortable. Few reported receiving counseling or information
      about psychological distress from general medical providers (11%). These findings
      suggest that a significant number of adults across the country were continuing to
      experience terrorism-related distress and disruption of their daily lives
      approximately 2 months after September 11; many turned to family and friends for
      support, but at times many felt uncomfortable doing so, and few used clinicians
      as a source of information or support. Clinicians and policymakers should
      consider how the healthcare system and other community organizations might
      provide a coordinated community-wide response for individuals needing information
      and counseling following terrorist events.

PMID- 15262578
TI  - Fighting the psychological war on terrorism.

PMID- 15262579
TI  - The power of the pink ribbon: Raising awareness of the mental health implications
      of terrorism.

PMID- 15262580
TI  - Lessons learned since September 11th 2001 concerning the mental health impact of
      terrorism, appropriate response strategies and future preparedness.

PMID- 15262581
TI  - When being upset is not a mental health problem.

PMID- 15262582
TI  - The social context of recovery.

PMID- 15262583
TI  - Can we influence the trajectory of psychological consequences to terrorism?

PMID- 15262584
TI  - Preparing for terrorist attacks: an ongoing challenge.

PMID- 15262585
TI  - Responses to trauma: normal reactions or pathological symptoms.

PMID- 15262586
TI  - Further lessons from 9/11: does stress equal trauma?

PMID- 15262587
TI  - Culture and formulations of homicide: two case studies.
AB  - The killing of another human being is an execrable act and universally condemned.
      Simpler societies have informal ways of seeking retribution (Bohannan 1960;
      Hoebel 1954). Ancient states and civilizations evolved formal procedures and
      complex institutions for evaluating culpability, apportioning blame, and
      authorizing appropriate sanctions (Ng 1990; Robinson 1996). The evolution of the
      insanity defense in Anglo-American society has culminated in assigning to
      psychiatry and psychology the important task of determining whether the mental
      state of a person who perpetuates homicide meets criteria for legal sanction.
      Differences involving the traditional model of reasoning about human action that
      is standard in psychiatry compared to law have been discussed. A common basis of
      understanding and procedure for assessing responsibility has evolved (Moore
      1984). However, usually neglected is the influence that culture has in shaping
      behavior of homicide and its forensic psychiatric assessment. Two cases are
      presented to examine why and how culture is influential in matters of homicide.

PMID- 15262588
TI  - Expressed emotion, attribution, and control in parents of schizophrenic patients.
AB  - Expressed emotion is a measure of an individual's critical and/or emotionally
      overinvolved attitudes toward another person. The characteristics of parents who
      are high in expressed emotion are not fully understood. This study examined some
      variables potentially associated with expressed emotion, as measured by the
      Camberwell Family Interview, in 54 parents of schizophrenic young adults.
      Statements of (1) self-blame for the patient's illness, (2) controlling behaviors
      toward the patient, and (3) controlling behaviors toward others were assessed. As
      predicted, parents who blamed themselves for the patient's illness had higher
      emotional overinvolvement ratings than non-self-blaming parents. Measures of
      controlling behavior revealed that highly critical parents were not more
      controlling than less critical parents; however, parents high in emotional
      overinvolvement reported higher levels of patient- and other-controlling
      behaviors than parents low in emotional overinvolvement. These results suggest
      that the emotional overinvolvement component of high expressed emotion is
      associated with self-blaming attributions and controlling behaviors in parents,
      but that the criticism component is not.

PMID- 15262590
TI  - The abyss becoming well: psychoanalysis and reversals in perspective.

PMID- 15262591
TI  - The Achilles complex: preoedipal trauma, rage and repetition.

PMID- 15262592
TI  - Mourning, trauma and working through.

PMID- 15262593
TI  - Rachmaninoff's emotional collapse and recovery: the first symphony and its
      aftermath.

PMID- 15262594
TI  - I hear you knocking but you can't come in: two reasons to refuse the good object.

PMID- 15262595
TI  - Affective development, education and prevention: a psychodynamic model.

PMID- 15262596
TI  - R.O.T.: north by northwest.

PMID- 15262597
TI  - Re: "The cure of souls in the therapeutic state.".

PMID- 15262598
TI  - Off-pump coronary artery bypass grafting in a high-risk dextrocardia patient: a
      case report.
AB  - We present an interesting but high-risk case of an obese male patient aged 56
      years with dextrocardia and a left diaphragmatic hernia. Anterior myocardial
      infarction was diagnosed in 1994, and the patient later presented with a history
      of unstable angina. The diagnosis for this chronic smoker was triple-vessel
      disease, impaired left ventricular function, chronic renal failure, chronic
      bronchitis, impaired lung function, pulmonary hypertension, hypertension,
      diabetes, and chronic active gastritis (EuroSCORE of 10). The patient underwent
      successful off-pump coronary artery bypass grafting with 3 saphenous vein grafts
      to the left anterior descending, obtuse marginal, and right posterior descending
      arteries. He was discharged home 8 days later.

PMID- 15262599
TI  - Postoperative nesiritide use following high-risk mitral valve replacement.
AB  - Nesiritide is primarily used in the treatment of acutely decompensated chronic
      heart failure. It may also be useful in the postoperative management of patients
      with an exacerbation of heart failure after cardiac surgery. The management of a
      patient with cardiogenic shock after acute papillary muscle rupture is described.
      The patient exhibited signs of postoperative heart failure, and nesiritide
      therapy was instituted to lower filling pressures and achieve diuresis. This drug
      may be useful when patients with heart failure undergo cardiac surgery and
      continue to show evidence of heart failure in the postoperative period.

PMID- 15262600
TI  - Platelet function changes as monitored by cone and plate(let) analyzer during
      beating heart surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) is believed to reduce
      cardiopulmonary bypass (CPB)-related complications, including platelet damage. A
      hypercoagulable state instead of coagulopathy has been reported following OPCAB
      surgeries due to CPB. Whether platelet function is changed when the injurious
      effect of CPB is eliminated was investigated. METHODS: Platelet function was
      determined with the cone and plate(let) analyzer (CPA) method. The 2 parameters,
      average size (AS) and surface coverage (SC) of platelet aggregates, were measured
      with the CPA method to assess platelet aggregation and adhesion. These parameters
      were evaluated, and their values were compared at several stages of OPCAB
      surgery. The correlations of postoperative bleeding with platelet function at
      different stages of the surgery and with other factors, such as platelet count,
      hematocrit, and transfusions, were studied. RESULTS: Both AS and SC increased
      during several stages of the operation, and postoperative values (mean +/- SD)
      were significantly higher than preoperative values (30.4 +/- 8.1 microm 2 versus
      23.3 +/- 6.9 microm 2 for AS [ P =.02] and 7.6% +/- 3.6% versus 5.2% +/- 1.8% for
      SC [ P =.04]). The mean total bleeding volume was 875 micro 415 mL. Preoperative
      AS and SC were the only parameters significantly ( P =.01) and linearly ( r =
      0.7) related to postoperative bleeding. CONCLUSIONS: An increased platelet
      function, as determined by the CPA method, is found following OPCAB surgery. This
      phenomenon is probably at least partially responsible for the thrombogenic state
      after OPCAB surgery. Lack of platelet injury attributed to CPB may divert the
      system toward a more thrombogenic state. Preoperative platelet function, as
      evaluated by the CPA method, is an independent risk factor determining
      postoperative bleeding.

PMID- 15262601
TI  - Minimally invasive aortic valve replacement under thoracic epidural anesthesia in
      a conscious patient: case report.
AB  - Cardiopulmonary bypass and full median sternotomy have been recognized as major
      morbidity factors in cardiac surgery. Additional morbidity factors are general
      anesthesia and endotracheal intubation. Over the past several years high-thoracic
      epidural anesthesia (hTEA) has emerged as a potentially beneficial supplement to
      general anesthesia in the care of patients undergoing cardiac surgery. We report
      a case of ministernotomy aortic valve replacement performed with hTEA. The
      procedure was not converted to general anesthesia or to a conventional operation
      and was performed without adverse incidents. The patient was discharged from the
      hospital on the 2nd postoperative day. There were no complications within 30 days
      after surgery. This case demonstrates that thoracic epidural anesthesia without
      endotracheal intubation used for aortic valve replacement performed through
      ministernotomy is feasible. Further experience is necessary to determine the
      safety of this method and the effect on outcome.

PMID- 15262602
TI  - Successful surgical management of a double-chambered left ventricle in a 13-year
      old girl: a report of a rare case.
AB  - BACKGROUND: Double-chambered left ventricle (DCLV) is a rare congenital anomaly,
      and only a few cases in which a 2-chambered LV is separated by the
      interventricular septum or an abnormal muscle bundle have been reported in the
      literature. Frequently, such cases are diagnosed when a patient is admitted to
      hospital for the evaluation of a cardiac murmur, and most of these patients have
      isolated DCLV. MATERIALS AND METHODS: We describe the case of a 13-year-old girl
      with DCLV who had twice undergone operation, including mitral valve replacement,
      in our institution. RESULT: No gradient was found after surgical resection of the
      hypertrophic floating mass, and the patient's symptoms disappeared. DISCUSSION:
      Surgical resection can be carried out in patients with DCLV when done
      sufficiently early, and careful echocardiographic examination is important in a
      continuing follow-up. Surgeons should keep in mind the possibility of a
      recurrence of DCLV.

PMID- 15262603
TI  - Partial clamping of the brachiocephalic trunk for total ascending aorta
      replacement without circulatory arrest: early and midterm results.
AB  - BACKGROUND: The aim of this study was to evaluate in elective patients the early
      and midterm results of partial clamping of the brachiocephalic trunk (BCT) for
      total ascending aorta replacement (TAAR) without circulatory arrest.
      Contraindications to the procedure were BCT/aortic arch calcifications and
      chronic aortic dissection. METHODS: The right radial artery was cannulated to
      monitor the systemic pressure after the BCT was partially clamped. A specially
      designed clamp was applied obliquely to occlude approximately 50% of the BCT and
      part of the aortic arch. The distal tip of the clamp was positioned in front of
      the left subclavian artery. From January 2002 to October 2003, 92 patients
      underwent TAAR. In 62 patients (67.4%), partial clamping of the BCT was used.
      Twenty of these patients underwent isolated TAAR, 27 underwent aortic valve
      replacement and TAAR, 11 had a Bentall operation, and 2 had a Cabrol operation.
      The aortic valve was spared in the remaining 2 patients. The mean (+/- SD) aortic
      cross-clamping and cardiopulmonary bypass times were 96 +/- 31 minutes and 116 +/
      43 minutes, respectively. RESULTS: Early mortality was 1.6% (1 patient). No
      cerebrovascular accidents occurred, demonstrating the safety of the technique.
      The major complications were acute respiratory insufficiency in 2 cases and acute
      renal failure in 5. The mean follow-up time was 9.0 +/- 6.5 months. The mean 18-
      month and event-free survival rate was 96.6% +/- 0.9%. CONCLUSION: Partial
      clamping of the BCT for TAAR without circulatory arrest provides good early and
      midterm clinical results. Aortic arch clamping is not associated with
      cerebrovascular accidents.

PMID- 15262604
TI  - Spinal (subarachnoid) morphine for off-pump coronary artery bypass surgery.
AB  - OBJECTIVE: To study the effects of 8 microg/kg preoperatively administered
      intrathecal morphine sulfate on extubation time, postoperative pulmonary
      function, and postoperative analgesia after off-pump coronary artery bypass
      grafting (OPCAB). DESIGN: A prospective, randomized, double-blind, placebo
      controlled study. PARTICIPANTS: One hundred adult patients scheduled for elective
      primary OPCAB. INTERVENTIONS: Patients were randomized to preoperative
      administration of 8 microg/kg intrathecal morphine sulfate (group 1) with a 25
      gauge spinal needle or to receive sterile normal saline placebo subcutaneously
      (group 2). Anesthetic induction and maintenance were standardized to allow
      planning for facilitating early tracheal extubation. Multivessel OPCAB was
      performed with an Octopus stabilizer. Patients were extubated in the intensive
      care unit by a blinded observer using predefined extubation criteria.
      MEASUREMENTS AND MAIN RESULTS: Postoperative times to extubation were 9.47 +/-
      3.83 hours in group 1 versus 11.25 +/- 3.94 hours in group 2 (P = .025).
      Postextubation bedside spirometric lung volumes in percentage of preoperative
      lung volume showed significant differences in group 1 versus group 2 in forced
      vital capacity, 39.66% +/- 15.42% versus 31.85% +/- 11.65% (P = .016); forced
      expiratory volume in the first second, 44.8% +/- 16.18% versus 35.97% +/- 13.32%
      (P = .013); maximum voluntary ventilation, 39.40% +/- 13.57% versus 33.11% +/-
      14.80% (P = .056); and expiratory flow rate, 47.76% +/- 24.61% versus 37.37% +/-
      4.33% (P = .031). The visual analog pain scores at rest and during coughing at
      time intervals of 6, 12, 24, and 36 hours postoperatively showed significantly
      better results in group 1 compared with group 2. The total dose of fentanyl
      citrate required intraoperatively was significantly less in group 1 (P = .00).
      One patient in group 1 had a low respiratory rate, which responded to injection
      naloxone. There was no mortality or neurological complication in either group.
      CONCLUSION: Intrathecal morphine provided superior quality of analgesia that
      translated into better maintenance of postoperative lung volume determined by
      spirometry. This analgesic method also facilitated earlier tracheal extubation
      without any major respiratory or neurologic complications.

PMID- 15262605
TI  - Long-term arm morbidity after radial artery harvesting for coronary bypass
      operation.
AB  - BACKGROUND: The use of the radial artery (RA) in coronary bypass operations has
      become increasingly popular in recent years, but there is almost no documentation
      regarding the midterm and long-term arm complications. METHODS: Between January 1
      and December 31, 1998, 109 patients underwent operations for myocardial
      revascularization employing a pedicled RA as 1 of the coronary grafts. The
      patients were surveyed for subjective arm morbidities at 2 times during their
      follow-up: short term (mean, 7 months postoperatively; range, 0.3-14 months) and
      long term (mean, 49 months postoperatively; range, 46-57 months). RESULTS: At the
      short-term follow-up, 33 (33.3%) of the patients had some complaints regarding
      the arm that was operated on, with 4 (4%) of the patients reporting arm
      disability with complaints that focused on pain (11, 11%), numbness (15, 15%),
      and parasthesias (12, 12%). At the longterm follow-up, only 9 patients (10.5%)
      still experienced some sort of inconvenience with the arm that was operated on,
      with 1 case of functional disability, 4 complaints (4.6%) of residual
      parasthesias, and 1 report (2.3%) each of pain or numbness. All but 2 of the
      patients with complaints at the short-term follow-up reported amelioration of
      symptoms at the long-term follow-up. CONCLUSION: It appears that severe arm
      disability early after RA harvesting is likely to dissolve with time. Our
      favorable late follow-up results support the continuation of the employment of
      the RA as a conduit for coronary artery bypass grafting operations.

PMID- 15262606
TI  - Editorial: Patency in off-pump coronary artery bypass graft surgery.

PMID- 15262607
TI  - Minimally invasive concomitant cardiac procedures and repair of pectus excavatum:
      case report.
AB  - A minimally invasive concomitant repair of an atrial-septal defect II with patent
      ductus arteriosus and pectus excavatum, using a substernal steel bar was
      successfully done in a 10-year-old girl. Postoperative outcomes and cosmetic
      appearance were excellent. Therefore, a simultaneous repair of pectus excavatum
      with cardiac lesions performed in a minimally invasive way is feasible and should
      be considered, particularly in female children.

PMID- 15262608
TI  - Transmyocardial laser therapy: a strategic approach.
AB  - BACKGROUND: Coronary artery bypass and percutaneous intervention have become the
      established methods of coronary revascularization in treating angina pectoris.
      Subsets of angina patients, however, are not amenable to either of these
      procedures. Transmyocardial laser revascularization (TMR) has been developed as a
      potential treatment to address such patients, and clinical research to date
      illustrates the success of TMR for this patient group. STRATEGIC PLAN SUMMARY:
      Although the symptoms of ischemic heart disease manifest themselves in a variety
      of ways, the best results with TMR are seen in patients with severe angina rather
      than in patients with silent ischemia or congestive heart failure. Potential TMR
      patients receive diagnostic tests to determine if and where the therapy should be
      applied. A recent cardiac catheterization is required to document the status of
      and the coronary-system suitability for the planned intervention. It is not
      appropriate to assume that a patient with nonbypassable, noninterventional
      coronary artery disease has to be relegated to medical therapy only.
      Additionally, echocardiography demonstrates the status of cardiac valves and
      segmental wall motion activity. This knowledge allows the surgeon to determine
      the sequence of surgery and if abnormalities are present. Once the decision to
      use TMR use has been made, there are 2 approaches--sole therapy or adjunctive
      therapy. TMR is not to be substituted for a feasible bypass graft, but the best
      time to make this decision may well be during the surgery itself, because grafts
      that appear surgically feasible on an angiogram may be less feasible after the
      chest has been opened. The decision to perform sole-therapy TMR in the absence of
      bypassable vessels clearly must be made before opening the chest. Whether to use
      cardiopulmonary bypass (CPB) and the sequence in which to perform TMR and bypass
      grafts are based on surgeon preference. The advantage of performing TMR on CPB is
      that channels can quickly be lased without pause. A potential advantage of
      performing TMR before bypass grafts is that "channel leak" (bleeding) can be
      minimized by the conclusion of the surgery. Complete revascularization has become
      technically more difficult because of the increasing use of percutaneous
      approaches and because patients are being referred for coronary artery bypass
      grafting much later in the course of their coronary disease progression than
      before. TMR may well be a viable alternative to bypassing a heavily diseased,
      previously intervened, small-diameter coronary artery. Thus, a model in which
      myocardial perfusion is considered within the context of the natural circulation
      can be conceived as an alternative to a model in which circulation is altered by
      interventional, surgical, and/or transmyocardial methods. TMR has been shown to
      be effective in accomplishing a complete revascularization when the restoration
      of circulation to ischemic territories with interventional therapy, bypass
      surgery, or a combination of both has been ineffective. We recommend that
      interested users follow this "complete revascularization strategy" algorithm for
      all ischemic vessels being considered for interventional or surgical treatment.
      Running each diseased vessel through this thought process will ensure that
      available treatment options are considered in the optimization of a patient's
      outcome. CONCLUSION: The use of TMR for angina relief has evolved into a
      clinically proven technology that has enabled physicians to address difficult
      revascularization cases with a therapy that is safe and effective.

PMID- 15262609
TI  - Midterm results after septal reshaping for anteroseptal scars.
AB  - BACKGROUND: Midterm clinical and morphologic results of the septal-reshaping
      exclusion of anteroseptal dyskinetic or akinetic areas were evaluated. METHODS:
      From January to June 2003, 44 patients with myocardial infarction following left
      anterior descending coronary artery (LAD) occlusion underwent septal reshaping.
      The mean (+/- SD) New York Heart Association (NYHA) class of the patients at
      admission was 2.7 +/- 0.9. Angina was referred in 21 cases. The incision was
      started at the apex and directed parallel to the LAD toward the base of the
      heart. The septum was rebuilt with 1 or 2 U-stitches passed from the inside to
      join the anterior wall to the septum by starting as high as possible where the
      scar began and continuing in an oblique direction toward the new apex. An oval
      polyethylene terephthalate fiber (Dacron) patch was then sutured from the septum
      (at the end of the direct suture through the border with the inferior septum) to
      the anterior wall (between the healthy wall and the scarred wall) and up to the
      new apex. RESULTS: The 30-day mortality rate was 2.2% (1 patient, due to the
      failure of a previously implanted defibrillator). Three patients experienced
      acute renal failure. No patient had restrictive syndrome. After a mean follow-up
      period of 8.5 +/- 4.9 months (range, 4-22 months), the mean NYHA class improved
      from 2.7 +/- 0.9 to 1.6 +/- 0.5 (P < .001). The 18- month survival rate and the
      probability of being alive in NYHA class I or II were 93.2% +/- 2.0% and 90.9% +/
      4.3%, respectively. Echocardiographic results showed reductions in the left
      ventricle volume with a normalization of the stroke volume. The diastolic
      longitudinal length remained unchanged, and the diastolic sphericity index was
      reduced but not significantly. CONCLUSIONS: At 1 year after surgery, the good
      clinical and morphologic results demonstrate the safety and effectiveness of
      septal reshaping for anteroseptal scars.

PMID- 15262610
TI  - Complications following placement or extraction of endovascular pacemaker and
      defibrillator leads--cardiothoracic surgical intervention: case reports.
AB  - Complications related to the insertion or removal of permanent pacemakers and
      implantable cardiac defibrillators are rare events. However, when adverse events
      occur, their severity may be life threatening. Rapid recognition of a problem
      followed by prompt consultation with a cardiothoracic surgeon is necessary to
      stabilize potentially catastrophic events. The immediate availability of surgical
      instruments as well as a formalized algorithm for management is necessary to
      control hemorrhagic situations. Four case reports illustrate these points.

PMID- 15262611
TI  - Early experience with a new aortic clamping system designed for port access
      cardiac surgery: the PortaClamp.
AB  - BACKGROUND: We report a clinical study to demonstrate the feasibility and safety
      of a new aortic crossclamping concept for use in port-access cardiac surgery. The
      limited access to the aorta in minimally invasive cardiac surgery mandates
      specific clamping modalities, which entail specific limitations, drawbacks, and
      costs. Therefore a new autoguided, extravascular, and atraumatic clamping system
      (PortaClamp) was developed to facilitate port-access surgery while potentially
      avoiding the complications and costs inherent to endoluminal clamping or "blind"
      crossclamping. METHODS: Twenty patients underwent various cardiac operations
      under cardiopulmonary bypass and aortic crossclamping with the PortaClamp between
      February and September 2003. The method of aortic clamping is described and the
      operative course and clinical outcome of the patients are reported as surrogates
      of feasibility and safety. RESULTS: The average time to position the clamp was
      196 +/- 75 seconds. Crossclamping through a 10-mm port or incision was achieved
      successfully, enabling cardiac arrest throughout the procedure in every patient.
      No patient presented with cardiovascular accident or transient ischemic attack,
      aortic dissection, or hematoma. Intensive care unit times were 12 +/- 3 hours;
      length of stay was 7.2 +/- 1.1 days. CONCLUSION: From this early experience we
      conclude that the PortaClamp system is safe and can effectively be used to
      crossclamp the aorta inexpensively to facilitate port-access cardiac surgery.
      Further comparative studies with the existing systems are warranted to confirm
      that the atraumatic design provides further benefit.

PMID- 15262612
TI  - Preoperative computed tomography or intraoperative epiaortic ultrasound for the
      diagnosis of atherosclerosis of the ascending aorta?
AB  - BACKGROUND: Extensive atherosclerotic disease, usually first diagnosed
      intraoperatively, is the most important risk factor for postoperative stroke
      after cardiac surgery. The aim of this study was to investigate if preoperative
      computed tomography (CT) is comparable with intraoperative epiaortic ultrasound
      to diagnose severe atherosclerosis in the ascending aorta. METHODS: The study
      included 20 consecutive patients who underwent elective coronary artery bypass
      surgery. Preoperative CT evaluation of the ascending aorta was compared with
      intraoperative epiaortic ultrasound findings. The ascending aorta was divided
      into 12 segments per patient, giving 240 segments to compare. RESULTS: Epiaortic
      ultrasound detected atherosclerosis in 16.7% +/- 2.4% of the segments, a rate
      significantly higher than with CT ( P < or =.03). There was a low reliability
      between the 2 methods, indicated by kappa coefficients of 0.45 or lower.
      CONCLUSIONS: The CT method is inferior to epiaortic ultrasound, today's gold
      standard, in diagnosing the extent and location of atherosclerosis of the
      ascending aorta. Other methods, possibly magnetic resonance imaging, should be
      considered.

PMID- 15262613
TI  - The limiting factors for the transxiphoid approach in congenital cardiac surgery.
AB  - OBJECTIVE: Minimally invasive cardiac surgery is currently being performed for a
      wide variety of cardiothoracic procedures. Since August 1998, the transxiphoid
      approach using a direct cannulation to the ascending aorta has been selected for
      the closure of atrial septal defects (ASD) and ventricular septal defects (VSD)
      in our institution. However, this approach cannot be performed for all patients
      because of the small "xiphoid window." We analyzed the factors limiting this
      approach to determine the best factor predicting risk. METHODS: Of 26 patients
      who had an ASD or a VSD, 14 underwent complete repair using a transxiphoid
      approach. Preoperative data collected for all patients included the relationship
      between the right ventricular outflow tract and the lower sternum (the RVSA) in
      the cineangiograph. Multiple logistic regression analysis was used to investigate
      which of the factors best predicted whether the transxiphoid approach should be
      adopted. RESULTS: The factors best predicting this approach were the combination
      of RVSA and body surface area (BSA) (odds ratios of 2.982 [P = .018] and 0.925 [P
      = .046], respectively). With the logistic model used in a prospective study of 6
      consecutive patients, we were completely successful in predicting whether the
      transxiphoid approach could be performed. CONCLUSION: The combination of RVSA and
      BSA was the limiting factor for using the transxiphoid approach in congenital
      cardiac surgery.

PMID- 15262614
TI  - Anticipatory interpretations: addressing "cautionary tales" and the problem of
      premature termination.
AB  - This article explores the use of anticipatory interpretations early in the
      therapeutic process as a means of addressing the problem of premature termination
      with some patients. The author argues that emerging transference references,
      detected through a close attention to "cautionary tales" or derivative
      communications, should be used in early interpretive interventions. It is
      suggested that such transference references form a "template of intention" that
      help determine future difficulties in the therapeutic alliance. Being able to
      communicate these observations in a future-orientated way lays the groundwork for
      "thinking about" actions that threaten the therapeutic alliance when they occur,
      in turn curtailing the possibility of acting out through termination. The author
      uses two case examples to illustrate his observations and goes on to suggest that
      anticipatory interpretations involve: (1) isolating derivatives and underlying
      anxieties, (2) future-orientated transference references, and (3) an affirmation
      of difficulty.

PMID- 15262615
TI  - The Developmental Profile: its use in establishing indications for psychoanalytic
      treatment.
AB  - The Developmental Profile offers a description of the degree to which an adult
      has developed adaptive behavioral functions appropriate to his or her age and the
      extent to which his or her functioning is determined by "early," now maladaptive,
      patterns. After examining the structure, the application, and the psychometric
      evaluation of the Developmental Profile, the authors describe how this profile
      can be used to support the process of selecting a psychoanalytic treatment.

PMID- 15262616
TI  - Randomized controlled versus naturalistic studies: a new research agenda.
AB  - The present article addresses the question of what kind of evidence is required
      to demonstrate that a method of psychotherapy works. Referring to recent
      conceptualizations of the logical structure of scientific theories, that is, the
      structuralistic view of theories, the author shows that randomized controlled
      studies (RCTs) and naturalistic studies (effectiveness studies) refer to
      different domains of intended applications (laboratory vs. field). This view has
      several important implications: (1) RCTs and naturalistic studies do not differ
      concerning their internal and external validity; (2) naturalistic studies do not
      necessarily provide lower-level evidence than RCTs; (3) evidence from RCTs cannot
      be transferred to psychotherapeutic practice in the field; (4) naturalistic
      studies are required to demonstrate that a form of therapy works in the field;
      (5) The proposed catalogues for levels of evidence focus on RCTs; thus, they
      cannot be applied to the question if a therapy works in the field; (6) It is
      necessary to define separate criteria for levels of evidence of naturalistic
      studies; and (7) a new research agenda for naturalistic studies can be derived,
      which is analogous to that of efficacy studies. In this article, a proposal is
      made to define levels of evidence of naturalistic studies. A gold standard for
      naturalistic studies is proposed.

PMID- 15262617
TI  - Further thoughts on an experiential psychoanalytic approach to the Rorschach.
AB  - On the basis of the work of Schachtel and Mayman, the author previously outlined
      an experiential approach to the Rorschach that differed from both an empirical
      approach and a more classic psychoanalytic approach originally proposed by
      Rapaport. Herein, the author further describes that approach by focusing on the
      person of the assessor as he or she goes about interpreting a protocol. Borrowing
      from the treatment literature, the author discusses the processes involved,
      including the need to immerse oneself in the raw data, the internal split between
      the experiencing self and the observing self, and the role of empathy and
      reflection.

PMID- 15262618
TI  - Heightened interpersonal dependency in schizophrenia: associations with graver
      impairment in neurocognition but not with negative or positive symptoms.
AB  - This study sought to clarify how dependency traits may be related to
      neurocognition and clinical symptoms of schizophrenia. Participants were 35
      persons diagnosed with a schizophrenia-spectrum disorder who were recruited from
      a comprehensive day hospital at a VA Medical Center. Neurocognition, symptoms and
      level of interpersonal dependency were measured. Multiple regression analyses
      demonstrated that greater neurocognitive deficits predicted greater dependency
      needs. No relationship was found between symptoms and the level of dependency
      needs.

PMID- 15262619
TI  - The relationship between postpartum depression and abusive parenting behavior of
      Japanese mothers: a survey of mothers with a child less than one year old.
AB  - The relationships between postpartum depression and demographic characteristics,
      social support, marital relationship, negative and passive acceptance of the
      mother role, and parenting behavior were examined in 215 mothers who live in
      Tokyo, Japan, and who have a child less than 1 year old. Social support from
      husbands or friends and marital relationship were found to be significantly
      related to the Edinburgh Postnatal Depression Scale (EPDS) score. Although
      negative and passive acceptance of the mother role was also related to the EPDS
      score and neglectful parenting behavior, it was not found to be related to
      aggressive parenting behavior. The correlation between EPDS score and neglectful
      or aggressive parenting behavior was also significant, with aggressive parenting
      behavior more strongly related to the EPDS score.

PMID- 15262620
TI  - On the relation between sensory input and action.
AB  - The role of sensory return in movement has recently been considered in relation
      to models involving feedforward control and in the comparison of predicted and
      actual states. The author suggests that sensory feedback may also have other
      effects at the level of movement initiation. The experiences of 3 individuals
      with differing impairments are reported, 1 with acute withdrawal of movement and
      position sense, 1 with acute meningitis, and the 3rd after prolonged
      immobilization following a heel injury. All were surprised to find difficulty in
      turning an intention to move into action in the affected body areas. One
      suggested that he had "forgotten what to do," even though the original injury had
      healed. The path from intention to movement may be dependent on feedback from the
      peripheral sensory apparatus at levels below attention, at least until voluntary
      action is required.

PMID- 15262621
TI  - Saccadic output is influenced by limb kinetics during eye-hand coordination.
AB  - In several recent studies, saccadic eye movements were found to be influenced by
      concurrent reaching movements. The authors investigated whether that influence
      originates in limb kinematic or kinetic signals. To dissociate those 2
      possibilities, the authors required participants (N = 6) to generate pointing
      movements with a mass that either resisted or assisted limb motion. With
      practice, participants were able to generate pointing responses with very similar
      kinematics but whose kinetics varied in a systematic manner. The results showed
      that saccadic output was altered by the amount of force required to move the arm,
      consistent with an influence from limb kinetic signals. Because the interaction
      occurred before the pointing response began, the authors conclude that a
      predictive signal related to limb kinetics modulates saccadic output during tasks
      requiring eye-hand coordination.

PMID- 15262622
TI  - Prepared movements are elicited early by startle.
AB  - A startle stimulus has been shown to elicit a ballistic response in a reaction
      time (RT) task at very short latencies without involvement of the cerebral cortex
      (J. Valls-Sole, J. C. Rothwell, F. Gooulard, G. Cossu, & E. Munoz, 1999). The
      present authors examined the nature of the startle response. A simple RT task was
      used in which 8 participants performed arm extension movements to 3 target
      distances (20 degrees, 40 degrees, and 60 degrees ) in a blocked design. An
      unpredictable startling acoustic stimulus (124 dB) replaced the imperative
      stimulus in certain trials. The authors verified the presence of a startle
      response independent from the prepared response by observing electromyographic
      (EMG) activity in sternocleidomastoid and orbicularis oculi muscles. Findings
      indicated that when the participant was startled, the intended voluntary response
      was produced at significantly shorter response latencies. Furthermore, the
      kinematic variables of the observed response during startle trials for all 3
      target distances were mostly unchanged. The EMG characteristics of the responses
      were not modified, indicating that the response produced was indeed the prepared
      and intended response.

PMID- 15262623
TI  - Amplitude scaling in a bimanual circle-drawing task: pattern switching and end
      effector variability.
AB  - The authors manipulated movement amplitude in a bimanual circle-tracing task
      performed by 11 participants. With pacing frequency fixed, the systematic
      increase and decrease of circle diameter within a trial induced phase transitions
      from the asymmetric (33% of trials) to the symmetric bimanual circle-tracing
      pattern; the transitions resulted from a loss of stability in the asymmetric
      pattern. Tracing frequency varied inversely with circle diameter so that end
      effector variability was minimized in a set of self-paced trials in which the
      circle diameter in a trial was fixed. In the amplitude-scaling trials, end
      effector variability varied directly with circle diameter, a consistent speed
      accuracy tradeoff. The results support the conclusion that movement amplitude is
      a nonspecific control parameter. The findings are discussed with reference to
      several factors, e.g., tactile feedback, the recruitment and suppression of
      biomechanical degrees of freedom, and the role those factors may play in
      stabilizing bimanual coordination patterns

PMID- 15262624
TI  - Specificity of practice, visual information, and intersegmental dynamics in rapid
      aiming limb movements.
AB  - The authors tested the specificity of practice hypothesis on intersegmental
      dynamics of rapid-aiming limb movements. During acquisition, 20 participants
      performed an aiming task as quickly and accurately as possible either with or
      without vision. Following moderate (140 trials) and extensive (560 trials)
      practice, participants completed 20 transfer test trials in a no-vision
      condition. Overall, the acquisition-phase findings revealed that vision improved
      aiming accuracy performance but had only a slight impact on movement time and
      intersegmental dynamics. After 560 trials of practice, however, withdrawal of
      vision resulted in specificity of practice effects on intersegmental dynamics at
      the shoulder as well as on aiming accuracy. Taken together, those findings
      support and extend the specificity of practice hypothesis

PMID- 15262625
TI  - First-trial adaptation to prism exposure: artifact of visual capture.
AB  - Terminal target-pointing error on the 1st trial of exposure to optical
      displacement is usually less than is expected from the optical displacement
      magnitude. The authors confirmed 1st-trial adaptation in the task of pointing
      toward optically displaced targets while visual feedback was delayed until
      movement completion. Measurement of head-shoulder posture while participants (N =
      24) viewed the optically displaced field revealed that their shoulders felt
      turned in the direction opposite to the displacement (visual capture), accounting
      for all but about 4% to 10% of 1st-trial adaptation. First-trial adaptation was
      unrelated to realignment aftereffects. First-trial adaptation is largely an
      artifact of the asymmetry of the structured visual field produced by optical
      displacement, which induces a felt body rotation, thereby reducing the effective
      optical displacement.

PMID- 15262626
TI  - Variations of tool and task characteristics reveal that tool-use postures are
      anticipated.
AB  - The authors examined anticipation in tool use, focusing on tool length and tool
      use posture. Adults (9 women and 9 men in each experiment) held a rod (length 0.4
      0.8 m), with the tip upward; walked toward a cube; chose a place to stop; and
      displaced the cube with the rod's tip. In 2 experiments, rod length, mass, and
      mass distribution, and the size of the cube were manipulated. Chosen distance
      depended on rod length and cube size. Because effects of cube size on distance
      resulted only from postural changes related to required control, distance
      anticipated displacement posture. A postural synergy comprising legs and trunk
      provided a stable platform for the displacement. An arm synergy was less extended
      for small cubes, longer rods, and handle-weighted rods. Selected distance
      anticipated those postures.

PMID- 15262627
TI  - Anticipatory postural adjustments for altering direction during walking.
AB  - The authors examined how individuals adapt their gait and regulate their body
      configuration before altering direction during walking. Eight young adults were
      asked to change direction during walking with different turning angles (0 degree,
      45 degree, 90 degree), pivot foot (left, right), and walking speeds (normal and
      fast). The authors used video and force platform systems to determine
      participants' whole-body center of mass and the center of pressure during the
      step before they changed direction. The results showed that anticipatory postural
      adjustments occurred during the prior step and occurred earlier for the fast
      walking speed. Anticipatory postural adjustments were affected by all 3 variables
      (turn angle, pivot foot, and speed). Participants leaned backward and sideward on
      the prior step in anticipation of the turn. Those findings indicate that the
      motor system uses central control mechanisms to predict the required anticipatory
      adjustments and organizes the body configuration on the basis of the movement
      goal.

PMID- 15262628
TI  - Practice effects on the use of visual and haptic cues during grasping.
AB  - Mapping of arbitrary color cues onto object properties such as mass can influence
      the control of fingertip forces. One can view the development of that mapping as
      a motor learning issue, and its development should therefore be influenced by
      practice schedule. During an acquisition phase, 24 participants lifted color-cued
      objects that differed in mass. The masses were presented in either blocked or
      random orders. A test phase consisted of lifts of a midmass object; on some
      lifts, the object's mass was unexpectedly changed. The change was either
      accurately color cued or miscued. Only blocked practice led to visually mediated
      scaling of fingertip forces to object mass. During the test phase, previous
      blocked practice resulted in reliance on visual cues, and random practice led to
      a reliance on haptics (sense of touch). Those findings suggest that the
      integration of arbitrary color cues and haptic information is dependent on
      practice conditions.

PMID- 15262629
TI  - Learning to optimize speed, accuracy, and energy expenditure: a framework for
      understanding speed-accuracy relations in goal-directed aiming.
AB  - Over the last century, investigators have developed a number of models to explain
      the relation between speed and accuracy in target-directed manual aiming. The
      models vary in the extent to which they stress the importance of feedforward
      processes and the online use of sensory information (see D. Elliott, W. F.
      Helsen, & R. Chua, 2001, for a recent review). A common feature of those models
      is that the role of practice in optimizing speed, accuracy, and energy
      expenditure in goal-directed aiming is either ignored or minimized. The authors
      present a theoretical framework for understanding speed-accuracy tradeoffs that
      takes into account the strategic, trial-to-trial behavior of the performer. The
      strategic behavior enables individuals to maximize movement speed while
      minimizing error and energy expenditure.

PMID- 15262630
TI  - For it's a jolly good fellowship.

PMID- 15262631
TI  - Epidemiology and natural history of acute patellar dislocation.
AB  - BACKGROUND: The goals of this study were to (1) define the epidemiology of acute
      patellar dislocation, (2) determine the risk of subsequent patellar instability
      episodes (subluxation and/or redislocation) during the study period, and (3)
      identify risk factors for subsequent instability episodes. STUDY DESIGN:
      Prospective cohort study. METHODS: The authors prospectively followed 189
      patients for a period of 2 to 5 years. Historical data, injury mechanisms, and
      physical and radiographic measurements were recorded to identify potential risk
      factors for poor outcomes. RESULTS: Risk was highest among females 10 to 17 years
      old. Patients presenting with a prior history of instability were more likely to
      be female (P < .05) and were older than first-time dislocation patients (P <
      .05). Fewer first-time dislocators (17%) had episodes of instability during
      follow-up than patients with a previous history of instability (49%) (P < .01).
      After adjusting for demographics, patients with a prior history had 7 times
      higher odds of subsequent instability episodes during follow-up than first time
      dislocators (adjusted odds ratio = 6.6, P < .001). CONCLUSIONS: Patellar
      dislocators who present with a history of patellofemoral instability are more
      likely to be female, are older, and have greater risk of subsequent patellar
      instability episodes than first-time patellar dislocators. Risk of recurrent
      patellar instability episodes in either knee is much higher in this group than in
      first-time dislocators.

PMID- 15262632
TI  - Open versus closed kinetic chain exercises in patellofemoral pain: a 5-year
      prospective randomized study.
AB  - BACKGROUND: Today, no clinical studies have been undertaken to examine the long
      term effects of an open kinetic chain or closed kinetic chain program.
      HYPOTHESIS: The long-term follow-up results after a conservative exercise
      protocol are significantly worse than the short-term results. The long-term
      effect of closed kinetic chain training is significantly better compared to the
      effect of open kinetic chain training. STUDY DESIGN: Prospective randomized
      clinical trial. METHODS: Sixty patients were randomized into a 5-week
      conservative program, consisting of only closed kinetic chain exercises or only
      open kinetic chain exercises. Assessment of muscular characteristics, subjective
      symptoms, and functional performance was evaluated in this study at the time of
      initial physical examination, at the end of the treatment period, and 5 years
      later. RESULTS: At the 5-year follow-up, both groups demonstrated maintenance of
      good subjective and functional outcomes achieved immediately after the
      conservative treatment. No significant difference between both groups was
      observed at the 5-year follow-up for the majority of the examined parameters.
      However, on 3 of the 18 visual analog scales, the open kinetic chain group showed
      significantly less complaints compared to the closed kinetic chain group.
      CONCLUSIONS: On the basis of these results, the authors conclude that both open
      kinetic chain and closed kinetic chain programs lead to an equal long-term good
      functional outcome.

PMID- 15262633
TI  - The biomechanical effects of low-dose irradiation on bone-patellar tendon-bone
      allografts.
AB  - BACKGROUND: Despite evidence that low-dose irradiation of 2 Mrad (20 kGy) is not
      virucidal for patellar tendon allografts and reduces tissue strength, many tissue
      bank protocols include low-dose irradiation. HYPOTHESIS: Maintaining tissue
      mechanical integrity may be particularly relevant toward accelerated
      rehabilitation of the injured knee, where the cyclic function of patellar tendon
      allografts is critical. STUDY DESIGN: Controlled laboratory study. METHODS: The
      cyclic and failure mechanical properties of paired bone-patellar tendon-bone
      allografts, with and without current low-dose irradiation of 20 kGy, were
      evaluated. Specimens were loaded from 50 N to 250 N for 1000 cycles at 0.5 Hz and
      subsequently loaded to failure at a strain rate of 100% per second. RESULTS:
      After 1000 cycles, grafts elongated 27% more when irradiated than when not (4.4
      +/- 1.5 mm vs 3.4 +/- 1.0 mm; P = .03). Failure load averaged 1965 +/- 512 N for
      irradiated grafts and 2457 +/- 647 N for nonirradiated grafts (P = .007).
      CONCLUSIONS: The diminished strength of irradiated grafts may contribute to overt
      anterior cruciate ligament graft failure, and the increase in cyclic elongation
      may also be detrimental to graft function. CLINICAL RELEVANCE: These results
      suggest that one should consider the use of nonirradiated allografts as an
      alternative to irradiated grafts in anterior cruciate ligament reconstruction.

PMID- 15262634
TI  - Immediate effects of a knee brace with a constraint to knee extension on knee
      kinematics and ground reaction forces in a stop-jump task.
AB  - BACKGROUND: A small knee flexion angle in landing tasks was identified as a
      possible risk factor for noncontact anterior cruciate ligament injuries that are
      common in sports. HYPOTHESIS: A specially designed knee brace with a constraint
      to knee extension would significantly increase the knee flexion angle at the
      landing of athletic tasks preceded with horizontal movement components, such as
      stop-jump tasks. STUDY DESIGN: Repeated measure design for brace effects.
      METHODS: Three-dimensional videographic and force plate data were collected for
      10 male and 10 female recreational athletes performing a stop-jump task with and
      without the specially designed brace. Knee flexion angle at landing, maximum knee
      flexion angle, and peak ground reaction forces during the stance phase of the
      stop-jump task were determined for each subject with and without the knee brace.
      RESULTS: The knee brace decreased the knee flexion angle at the landing by 5
      degrees for both genders but did not significantly affect the peak ground
      reaction forces during the landing. CONCLUSIONS: The specially designed knee
      brace may be a useful device in the prevention and rehabilitation of noncontact
      anterior cruciate ligament injuries in sports.

PMID- 15262635
TI  - Effects of applied quadriceps and hamstrings muscle loads on forces in the
      anterior and posterior cruciate ligaments.
AB  - BACKGROUND: Muscle contraction can subject healing knee ligament grafts to high
      loads. PURPOSE: To directly measure the effects of quadriceps and hamstrings
      muscle loads on forces in the anterior cruciate ligaments and posterior cruciate
      ligaments. STUDY DESIGN: Controlled laboratory study. METHODS: Thirteen cadaveric
      knee specimens had load cells installed to record resultant forces in both
      anterior and posterior cruciate ligaments under 5 loading conditions. Cruciate
      force measurements were repeated with a 100-N load applied to the quadriceps
      tendon and again with a combined 50-N biceps load and 50-N semimembranosus
      semitendinosus load. RESULTS: Applied quadriceps loads resulted in mean changes
      in anterior cruciate ligament and posterior cruciate ligament forces that were
      less than 20 N for all loading conditions. Hamstrings load significantly
      increased mean posterior cruciate ligament force between 30 degrees and 105
      degrees of flexion with 100 N of applied posterior tibial force. CONCLUSIONS: At
      the muscle force levels used in this study, the hamstrings were more effective
      than the quadriceps in altering cruciate force levels, especially near 90 degrees
      of flexion, where they have an excellent mechanical advantage for controlling
      anterior-posterior tibial translation. CLINICAL RELEVANCE: Isolated hamstrings
      activity generally had little or no effect on anterior cruciate ligament forces
      but significantly increased forces in the posterior cruciate ligament beyond
      approximately 30 degrees of flexion.

PMID- 15262636
TI  - Knee laxity does not vary with the menstrual cycle, before or after exercise.
AB  - BACKGROUND: An intriguing explanation for the disproportionately high rate of
      anterior cruciate ligament injury in female athletes is that the structural
      properties of the anterior cruciate ligament are affected by the menstrual
      hormones. Whether this actually occurs, however, is the subject of ongoing
      debate. HYPOTHESES: (1) Anterior cruciate ligament laxity is different in the
      follicular, ovulatory, and luteal phases of the menstrual cycle, and (2) exercise
      exacerbates the difference in anterior cruciate ligament laxity in the 3 phases.
      METHODS: Over the course of 10 weeks, repeated knee laxity measurements were
      taken on 27 high-level female athletes, before and after exercise. Point in the
      menstrual cycle was determined with charts of waking temperature and
      menstruation. The independent effects of menstrual phase and exercise were
      evaluated using generalized estimating equations. RESULTS: Data from 18
      participants were included in the final analysis. There were no significant
      differences in anterior cruciate ligament laxity in any of the 3 menstrual
      phases, before or after exercise. CONCLUSIONS: Anterior cruciate ligament laxity
      is not significantly different during the follicular, ovulatory, and luteal
      phases of the menstrual cycle, and bicycling exercise does not exacerbate or
      create any differences in anterior cruciate ligament laxity.

PMID- 15262637
TI  - Ulnar collateral ligament reconstruction in high school baseball players:
      clinical results and injury risk factors.
AB  - BACKGROUND: The incidence of ulnar collateral ligament injury has increased in
      baseball, especially at the high school level. HYPOTHESIS: Ulnar collateral
      ligament injury in high school baseball players is associated with overuse, high
      velocity throwing, early throwing of breaking pitches, and improper warm-ups.
      STUDY DESIGN: Retrospective cohort study. METHODS: Follow-up physical examination
      and questionnaire data were collected at an average of 35 months after ulnar
      collateral ligament reconstruction from 27 former high school baseball players.
      Six potential risk factors were evaluated: year-round throwing, seasonal overuse,
      event overuse, throwing velocity more than 80 mph, throwing breaking pitches
      before age 14, and inadequate warm-ups. RESULTS: Overall, 74% returned to
      baseball at the same or higher level. Patients averaged 3 potential risk factors,
      and 85% demonstrated at least one overuse category. Of the pitchers, the average
      self-reported fastball velocity was 83 mph, and 67% threw breaking pitches before
      age 14. CONCLUSIONS: The success rate of ulnar collateral ligament reconstruction
      in high school baseball players is nearly equal to that in more mature groups of
      throwers. Overuse of the throwing arm and throwing breaking pitches at an early
      age may be related to their injuries. Special attention should be paid to elite
      level teenage pitchers who throw with high velocity.

PMID- 15262638
TI  - Glenohumeral arthrosis in anterior instability before and after surgical
      treatment: incidence and contributing factors.
AB  - BACKGROUND: Few large series of arthropathy related to anterior glenohumeral
      instability are available in the orthopaedic literature, preventing analysis of
      the incidence and the risk factors of preoperative and postoperative glenohumeral
      arthritis. HYPOTHESIS: Anterior stabilization surgery influences the risk factors
      of glenohumeral arthritis. STUDY DESIGN: Retrospective review. METHODS: There
      were 570 patients who underwent an instability procedure. Clinical and
      radiographic preoperative data were collected for these patients. Arthritis was
      evaluated preoperatively and postoperatively with the Samilson classification.
      The mean age at surgery was 31.9 years. Follow-up averaged 6.5 years. RESULTS:
      The preoperative incidence of arthritis was 9.2%. Arthritic risk factors were
      older age at the initial dislocation and at surgery, increased length of time
      from the initial dislocation until surgery, and the presence of osseous glenoid
      rim lesions. Postoperative arthritis in patients without any preoperative
      arthritis occurred in 19.7% and was correlated with older age at the initial
      dislocation and at surgery, increased number of dislocations, and longer follow
      up. Decreased external rotation at latest follow-up correlated with arthritis,
      although whether this was the cause or the effect was unclear. CONCLUSIONS:
      Similar factors contribute to preoperative and postoperative arthritis in
      patients with anterior glenohumeral instability, suggesting that surgery does not
      influence the risk factors of arthritis. Although decreased external rotation
      with the arm at side statistically correlated with arthritis in this study, the
      authors were unable to establish this as an effectual relationship because nearly
      all patients with glenohumeral osteoarthritis, whether instability related or
      not, have decreased external rotation.

PMID- 15262639
TI  - Semitendinosus regrowth: biochemical, ultrastructural, and physiological
      characterization of the regenerate tendon.
AB  - BACKGROUND: Previous studies have suggested that hamstring tendons can regenerate
      following harvesting for anterior cruciate ligament reconstruction. HYPOTHESIS:
      This "neo-tendon" is a true, functional tendon, not scar tissue. STUDY DESIGN:
      Controlled laboratory study. METHODS: Semitendinosus tendons were harvested from
      35 New Zealand white rabbits using a standard tendon stripper. The rabbits were
      sacrificed 9 to 12 months following the index procedure and thoroughly evaluated.
      RESULTS: Thirty-one rabbits were available at the time of sacrifice. The neo
      tendon was present in 26 rabbits but was highly variable in size and location of
      its tibial insertion. Histologic and immunohistochemical staining confirmed that
      the regenerate tissue was indeed tendon with normal cellularity, organization,
      and immunolocalization of type I collagen. Electron microscopy showed
      regeneration of organized collagen tissue that simulated native tendon but with a
      smaller cross-sectional diameter. Functionally, the neo-tendon was able to
      transmit force across the musculotendinous junction but at a significantly slower
      rate than the opposite, control leg. Biomechanical properties of the neo-tendon
      were significantly less than the control side. Biochemical analysis revealed that
      the neo-tendons contained glycosaminoglycans and collagen, but levels were
      significantly lower than normal tendons. CONCLUSIONS: Semitendinosus tendons
      regenerate with biologically reactive tendinous tissues in an animal model. This
      tissue has many of the characteristics of a normal tendon but appears to be
      inferior to the original musculotendinous unit at 9- to 12-month evaluation.
      Further characterization of the "lizard tail phenomenon" is still needed.
      CLINICAL RELEVANCE: Hamstring tendon regrowth may have a dramatic impact on
      postoperative function of patients who undergo anterior cruciate ligament
      reconstruction with these tendons. Further modulation of this regeneration may
      further reduce graft harvesting morbidity.

PMID- 15262640
TI  - Prosthetic replacement of the medial meniscus in cadaveric knees: does the
      prosthesis mimic the functional behavior of the native meniscus?
AB  - Meniscus replacement by a polymer meniscus prosthesis in dogs resulted in
      generation of new meniscal tissue. HYPOTHESIS: Optimal functioning of the
      prosthesis would involve realistic deformation and motion patterns of the
      prosthesis during knee joint motion. STUDY DESIGN: Controlled laboratory study.
      METHODS: The movements of the meniscus were determined during knee joint flexion
      and extension with and without internal and external tibial torque by means of
      roentgen stereophotogrammetric analysis. Subsequently, the meniscus in 6 human
      cadaveric knee joints was replaced by a meniscus prosthesis. RESULTS: All
      different parts of the meniscus showed a posterior displacement during knee joint
      flexion. The anterior horn was more mobile than the posterior horn. The
      prosthesis mimicked the movements of the meniscus. However, the excursions of the
      prosthesis on the tibial plateau were less. The knee joint laxity was not
      significantly higher after replacement with the meniscus prosthesis. CONCLUSIONS:
      The prosthesis approximated the behavior of the native meniscus. Improvement in
      both the gliding characteristics of the prosthetic material and the fixation of
      the prosthesis may improve the function. CLINICAL RELEVANCE: The meniscus
      prosthesis needs to be optimized to achieve a better initial function in the knee
      joint.

PMID- 15262641
TI  - Catastrophic injuries in high school and college baseball players.
AB  - BACKGROUND: There are few epidemiologic studies of catastrophic baseball
      injuries. PURPOSE: To develop a profile of catastrophic injuries in baseball
      players and to describe relevant risk factors. STUDY DESIGN: Retrospective cohort
      study. METHODS: The authors reviewed 41 incidents of baseball injuries reported
      to the National Center for Catastrophic Sports Injury Research from 1982 until
      2002. RESULTS: There were an estimated 1.95 direct catastrophic injuries per
      year, or 0.43 injuries per 100,000 participants. The most common mechanisms of
      injury were a collision of fielders (9) or of a base runner and a fielder (8), a
      pitcher hit by a batted ball (14), and an athlete hit by a thrown ball (4).
      Catastrophic injuries included 23 severe head injuries, 8 cervical injuries, 3
      cases of commotio cordis, and 2 cases each of a collapsed trachea and facial
      fractures. Three athletes sustained a severe head injury and facial fractures.
      Ten of the 41 injuries were fatalities. CONCLUSIONS: Suggestions for reducing
      catastrophic injuries in baseball include teaching proper techniques to avoid
      fielding and baserunning collisions, protecting the pitcher via a combination of
      screens and/or helmets with faceguards, continued surveillance and modifications
      of the bat and ball, eliminating headfirst slides, and continued analysis of
      chest protectors and automatic external defibrillators for commotio cordis.

PMID- 15262642
TI  - Differences in the ultimate strength of the biceps anchor and the generation of
      type II superior labral anterior posterior lesions in a cadaveric model.
AB  - BACKGROUND: The pathogenesis of superior labral anterior posterior lesions
      remains controversial. HYPOTHESIS: The biceps anchor is more vulnerable to
      loading with a posterior vector as opposed to an in-line pull. STUDY DESIGN:
      Controlled laboratory study. METHODS: Eight pairs of cadaveric shoulders were
      dissected, and the biceps tendon was loaded to failure in 1 of 2 loading
      patterns. Loading pattern A was meant to simulate the eccentric load of the
      biceps in the deceleration phase of throwing; loading pattern B was meant to
      simulate the posterior biceps load of the late cocking phase. RESULTS: The biceps
      anchor demonstrated significantly increased ultimate strength with in-line
      loading (group A, 508 N) as opposed to posterior loading (group B, 262 N, P <
      .001). All group B specimens failed at the biceps anchor, resulting in a type II
      superior labral anterior posterior lesion. Specimens in group A did not create a
      superior labral anterior posterior lesion. CONCLUSIONS: Direction of biceps
      loading resulted in significant differences in the ultimate strength of the
      biceps anchor and the generation of superior labral anterior posterior lesions.
      The biceps anchor was significantly weaker when loaded with a posterior vector.
      RELEVANCE: The superior labrum may be most vulnerable to injury in late cocking.
      The reproducible generation of type II superior labral anterior posterior lesions
      may have applications as a biomechanical model.

PMID- 15262643
TI  - Reducing the lateral force acting on the patella does not consistently decrease
      patellofemoral pressures.
AB  - BACKGROUND: Extensor mechanism procedures that decrease the lateral component of
      the patellar tendon or quadriceps force acting on the patella do not consistently
      reduce pain. HYPOTHESIS: Patellofemoral treatments do not consistently decrease
      patellofemoral pressures because of variations in the moments acting on the
      patella. STUDY DESIGN: Computer simulation study. METHODS: Computational models
      of 4 knees were constructed to characterize the patellofemoral pressure
      distribution during simulated squatting from 40 degrees to 90 degrees. The knees
      were given an initial Q angle of 25 degrees. Patellofemoral treatments were
      simulated by increasing the percentage of the quadriceps force applied by the
      vastus medialis by 50% and by medializing the tibial tuberosity to decrease the Q
      angle to 15 degrees. RESULTS: Decreasing the Q angle caused a larger decrease in
      the lateral component of the force applied by the quadriceps and patellar tendon
      than did increasing the force applied by the vastus medialis and, therefore, was
      more effective at decreasing patellofemoral pressures and the force needed to
      resist lateral subluxation. Both treatments also decreased the moments acting to
      rotate the distal patella laterally and tilt the patella laterally during
      flexion. Variations in these moments increased patellofemoral pressures for some
      knees. CONCLUSIONS: Treatments that reduce patellofemoral subluxation can have an
      unexpected influence on patellofemoral pressures because of the moments acting on
      the patella. CLINICAL RELEVANCE: Extensor mechanism procedures that restore
      patellofemoral stability may not provide pain relief.

PMID- 15262644
TI  - Active patellar tracking measurement: a novel device using ultrasound.
AB  - BACKGROUND: Many patients suffer patellar instability that may relate to
      transient patellar tracking abnormalities. OBJECTIVE: To develop and test a
      technique to measure dynamic patellar tracking. STUDY DESIGN: Controlled
      laboratory and in vivo study. METHOD: A functional knee brace was modified to
      allow an ultrasound transducer to be mounted laterally to the femur, following
      the path of the patella during knee movement. An ultrasound system was used to
      measure patellar mediolateral position parallel to the femoral transepicondylar
      axis. Ten subjects with no patellar instability were studied to obtain patellar
      tracking and accuracy data. RESULTS: The interobserver and intraobserver
      reproducibility ranged from 0.2 +/- 0.1 mm to 1.0 +/- 0.5 mm. The accuracy of the
      ultrasound measurement was checked against magnetic resonance imaging and was 0.6
      +/- 1.9 mm. The patella moved medially then laterally from extension to flexion
      when sitting. Squatting and stepping produced a more lateral path, without the
      initial medial translation. The patella was more lateral during knee extension
      than during flexion. CONCLUSIONS: This novel method for measurement of dynamic
      patellar mediolateral tracking was found to have good intraobserver and
      interobserver reproducibility, and the measurements matched closely with those
      obtained from magnetic resonance imaging reconstructions of static patellar
      positions. Some preliminary data for tracking in 3 activities were obtained from
      10 normal knees.

PMID- 15262645
TI  - Results of transphyseal anterior cruciate ligament reconstruction using patellar
      tendon autograft in tanner stage 3 or 4 adolescents with clearly open growth
      plates.
AB  - BACKGROUND: Drilling across the physes for intra-articular anterior cruciate
      ligament reconstruction is considered risky for skeletally immature patients.
      HYPOTHESIS: Skeletally immature patients with clearly open growth plates can
      safely undergo intra-articular anterior cruciate ligament reconstruction with
      patellar tendon autograft without suffering growth plate disturbance. STUDY
      DESIGN: Retrospective review of prospectively collected data. METHODS: Surgery
      involved drilling tunnels through the tibial and femoral physes, the bone plugs
      were placed proximal to the physes, and button fixation was placed on the cortex.
      Of 272 skeletally immature patients, 16 had clearly open growth plates. Tanner
      stage of physical development was evaluated. Follow-up evaluation included
      objective and subjective data. RESULTS: At the time of surgery, 7 patients were
      Tanner stage 3 and 9 were Tanner stage 4. Clinical follow-up (mean, 3.4 years
      after surgery) showed that the mean growth after surgery was 11.7 +/- 4.2 cm for
      boys and 6.6 +/- 2.3 cm for girls. No patients had growth plate disturbances,
      gross leg deformities, or gross leg-length discrepancies. Subjective results
      (mean, 5.6 years after surgery) showed a mean total score of 97.6 +/- 2.9 for the
      modified Noyes survey and 95.4 +/- 6.9 for the International Knee Documentation
      Committee survey. All patients returned to competitive sports after surgery.
      CONCLUSION: In 16 skeletally immature patients with clearly open growth plates
      who were Tanner stage 3 or 4, an intra-articular anterior cruciate ligament
      reconstruction was performed using a patellar tendon autograft with no gross
      growth disturbance; however, the surgical technique was meticulous for placing
      the bone plugs proximal to the physes, and the graft was not overtensioned.

PMID- 15262646
TI  - Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA
      levels are specifically altered in torn rotator cuff tendons.
AB  - BACKGROUND: Rotator cuff tears are a cause of pain and disability in the
      shoulder. The molecular changes associated with rotator cuff tearing are unclear.
      A subset of matrix metalloproteinases and tissue inhibitors of metalloproteinase,
      which are involved in extracellular matrix remodeling and degradation, were
      evaluated. HYPOTHESIS: There would be an increase in the mRNA level of specific
      matrix metalloproteinase and a decrease in the mRNA level of specific tissue
      inhibitors of metalloproteinase in rotator cuff tendon tissue obtained from
      patients with rotator cuff tears. STUDY DESIGN: Controlled laboratory study.
      METHODS: Tissue was obtained from 10 patients undergoing rotator cuff repair for
      full-thickness rotator cuff tears. Also, tissue was obtained from cadaveric
      specimens with no gross evidence of rotator cuff tearing. Reverse transcription
      polymerase chain reaction was performed for the collagenases (MMP-1, MMP-8, MMP
      13), the stromelysins (MMP-3, MMP-10, MMP-11), and the tissue inhibitors of
      metalloproteinase (TIMP-1, TIMP-2, TIMP-3, TIMP-4). Western blotting was
      performed to confirm the mRNA changes demonstrated in collagenase-3 (MMP-13).
      RESULTS: There was a significant increase in collagenase-3 (MMP-13) mRNA levels,
      a decrease in stromelysin-1 (MMP-3) mRNA levels, and a decrease in tissue
      inhibitor of metalloproteinase-2, -3, and -4 mRNA levels. Western blotting
      demonstrated an increase in the active form of collagenase-3 (MMP-13) in rotator
      cuff tendon tears. CONCLUSIONS: The mRNA levels of specific matrix
      metalloproteinases and tissue inhibitors of metalloproteinase are altered in torn
      rotator cuff tendons. CLINICAL RELEVANCE: With the known action of the matrix
      metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular
      matrix remodeling, these findings suggest that their roles in remodeling of
      rotator cuff tears should be further investigated.

PMID- 15262647
TI  - Primary repair of posterior cruciate ligament avulsion fracture: the effect of
      occult injury in the midsubstance on postoperative instability.
AB  - BACKGROUND: In the posterior cruciate ligament avulsion fracture, posterior
      instability cannot be completely restored by the anatomical reduction and
      fixation of an avulsed fragment. HYPOTHESIS: The occult midsubstance injury
      inside the posterior cruciate ligament may affect the residual posterior
      instability after anatomical reduction and internal fixation of the avulsed
      fragment. STUDY DESIGN: Prospective comparative clinical study. METHODS: Thirty
      one patients were followed for a period of 2 to 8 years. Based on magnetic
      resonance images taken immediately after the injury, these patients were divided
      into 2 groups, the occult injury group (group O, 15 knees) and the uninjured
      group (group N, 16 knees). RESULTS: The side-to-side difference of the posterior
      knee instability was 3.2 mm in group O and 3.0 mm in group N. Approximately 60%
      of the knees examined showed mild posterior instability in both groups. There
      were no significant differences found between the 2 groups. CONCLUSION: The
      occult posterior cruciate ligament midsubstance injury does not significantly
      affect postoperative posterior instability of the knee. This fact did not support
      the hypothesis that has been commonly considered thus far. CLINICAL RELEVANCE: It
      is not necessary for orthopaedic surgeons to be overly apprehensive about occult
      midsubstance injury in the treatment of posterior cruciate ligament avulsion
      fracture.

PMID- 15262648
TI  - Laparoscopic repair of groin pain in athletes.
AB  - BACKGROUND: There has been increasing interest regarding the cause and treatment
      of groin pain in athletes. The most common finding is a deficiency of the
      posterior wall of the inguinal canal, often repaired with bilateral inguinal
      myorrhaphy. HYPOTHESIS: Laparoscopic repair will offer a shorter convalescent
      period and better results as compared with open myorrhaphy. STUDY DESIGN:
      Retrospective review of prospectively collected data. METHODS: Between October
      1993 and October 2002, 131 athletes with groin pain unrelieved after 2 to 8
      months of conservative management underwent bilateral laparoscopic repair with
      the transabdominal preperitoneal technique for hernias. In 123 (94%) patients,
      physical examination revealed a dilated external ring, unilateral or bilateral,
      of the inguinal canal, and in 8 patients (6%) it was normal. RESULTS: During
      laparoscopy, a deficiency of the posterior inguinal wall was seen in all
      athletes. All patients left the hospital 24 hours after the procedure,
      discontinued oral analgesics within 72 hours of surgery, and were back to full
      sporting activities within 2 to 3 weeks. Four patients (3%) complained of thigh
      pain. After a mean follow-up of 5 years (range, 4 months to 10 years), there was
      1 recurrence (0.76%). CONCLUSIONS: Laparoscopic repair is an efficient method for
      the treatment of groin pain originating from a deficiency of the posterior
      inguinal wall, having fast recovery and excellent long-term results.

PMID- 15262649
TI  - Chondral resurfacing and high tibial osteotomy in the varus knee.
AB  - BACKGROUND: Treatment of patients with degenerative knees and varus malalignment
      presents a difficult clinical problem. HYPOTHESIS: Combining a medial opening
      wedge high tibial osteotomy with the microfracture chondral resurfacing procedure
      is a viable treatment option. STUDY DESIGN: Retrospective review of prospectively
      collected data. METHODS: A group of 38 consecutive patients (mean age, 51.3
      years; range, 34 to 72 years; 29 men and 10 women) with varus malalignment and
      chondral lesions who were treated with chondral resurfacing (an abrasion and
      microfracture technique) combined with a medial opening wedge high tibial
      osteotomy. All patients had >5 degrees of varus malalignment. Patients were
      evaluated preoperatively with the Lysholm and Western Ontario & McMasters
      Universities Osteoarthritis Index scoring systems and at a minimum of 2 years
      follow-up. RESULTS: Thirty-three of 38 patients (87%) were available for 2-year
      follow-up (average, 45 months; range, 24 to 80 months). Lysholm scores improved
      from a preoperative score of 43.5 to 78.0 at follow-up; Western Ontario &
      McMasters Universities Osteoarthritis Index scores improved from 45.8 to 16.2.
      The average Tegner score was 5.0. CONCLUSIONS: Combining a medial opening wedge
      high tibial osteotomy with the microfracture chondral resurfacing procedure in
      the varus knee is an effective method of decreasing pain and increasing function
      at a minimum of 2 years follow-up.

PMID- 15262650
TI  - Sagittal plane translation during level walking in poor-functioning and well
      functioning patients with anterior cruciate ligament deficiency.
AB  - BACKGROUND: Some patients with anterior cruciate ligament deficiency can function
      well and participate in high-level sports, whereas others have functional
      limitations even during activities of daily living. HYPOTHESIS: Patients who
      function well after an anterior cruciate ligament injury can stabilize the knee
      joint during gait by an anterior positioning of the tibia. STUDY DESIGN:
      Controlled laboratory study. METHODS: Sagittal tibial translation was registered
      with the CA-4000 electrogoniometer, during the Lachman test and walking, in 20
      patients with a unilateral anterior cruciate ligament injury. Eleven patients
      functioned well (Lysholm score > or = 84), and 9 patients had poor knee function
      (Lysholm score < 84). RESULTS: During gait, the well-functioning group had 24%
      greater anterior translation in the injured leg compared to the noninjured leg.
      In the poor-functioning group, the anterior translation in the injured leg was
      16% smaller compared to the noninjured leg (P = .0003). Tibial translation during
      the Lachman test was similar in the injured leg in the 2 groups. CONCLUSION:
      Patients who function well position their tibiae near the anterior border of the
      joint play. This position may encourage functional stability. CLINICAL RELEVANCE:
      Rehabilitation that emphasizes training to stabilize the tibia in an anterior
      position may improve functional stability of the anterior cruciate ligament
      deficient knee.

PMID- 15262651
TI  - Rupture of the pectoralis major muscle.
AB  - BACKGROUND: Total or near-total rupture of the pectoralis major muscle is a rare
      injury. Fewer than 200 cases have been reported in literature, many of them in
      single case reports. There is discrepancy regarding whether this kind of injury
      should be treated operatively. HYPOTHESIS: Early surgical treatment is necessary
      to obtain optimal functional recovery following total or near-total ruptures of
      the pectoralis major muscle. STUDY DESIGN: A case series of 33 operatively
      treated pectoralis major ruptures combined with a meta-analysis of the previously
      published cases in the English literature. METHODS: The authors have
      retrospectively analyzed 33 operatively treated cases of total or near-total
      ruptures of the pectoralis major muscle. They have also analyzed the previously
      published cases and the final outcomes of their treatment. The difference in
      outcome between groups of acute operation, delayed operation, and conservative
      treatment in both their own material and meta-analysis was statistically
      analyzed. RESULTS: Both the case series and the analysis of the cases from the
      literature showed that early operative treatment is associated with better
      outcome than delayed treatment. The delayed operation was associated with better
      outcome than the conservative treatment. CONCLUSION: Early surgical treatment by
      anatomic repair gives the best results in the treatment of total and near-total
      ruptures of the pectoralis major muscle.

PMID- 15262652
TI  - Effect of increased excursion of the ankle on the severity of acute eccentric
      contraction-induced strain injury in the gastrocnemius: an in vivo rat study.
AB  - BACKGROUND: Although muscle strain injury models are frequently employed, highly
      invasive procedures, including surgical intervention, are typically used to
      produce these models. In this study, a minimally invasive model of acute strain
      injury was produced with a single eccentric contraction. HYPOTHESIS: The authors
      tested whether the severity of strain injury in the in vivo gastrocnemius depends
      on the excursion of the ankle. STUDY DESIGN: Controlled laboratory study.
      METHODS: Animals were randomly assigned to 2 groups: a small range of motion
      group (90-105 degrees, n = 10) and a large range of motion group (90-125 degrees,
      n = 10). Tetanically activated gastrocnemius muscles with percutaneous electrical
      stimulation were simultaneously elongated by forced dorsiflexion of the ankle
      joint. RESULTS: Isometric tetanic force of the large range of motion group was
      significantly lower than the pretreatment control 1, 2, and 3 days after
      treatment. Such reduction was not observed in the small range of motion group.
      Apparent pathologic damage was observed in the large range of motion group
      throughout the study period of 10 days. CONCLUSIONS: A larger range of motion
      causes more damage in eccentric contraction by using the in vivo model. CLINICAL
      RELEVANCE: This in vivo model is useful to elucidate mechanisms of prevention and
      recovery of strain injury.

PMID- 15262653
TI  - Shoulder outcome measures: a comparison of 6 functional tests.
AB  - BACKGROUND: Several shoulder function scores are used in research, with no
      universally adopted standard. This study compares 6 shoulder outcome scales.
      HYPOTHESIS: Correlations exist between shoulder outcome scales, allowing
      conversion between scales. Shoulder scales are correlated with age. STUDY DESIGN:
      Regression and correlation study. METHODS: Seventy subjects with shoulder pain
      completed 6 shoulder outcome scales. Pearson correlations were calculated between
      the total scores of the 6 instruments, between the components of the scales, and
      with age. Regression equations were calculated between scales. RESULTS: The range
      of r values for total scores was 0.495 < or = r < or = 0.770, P < or = .01. In
      general, a scale's components were themselves highly correlated and added little
      new information to the scale (0.260 < or = r < or = 0.705, P < or = .05). Most of
      the scale scores were highly correlated with age (0.291 < or = r < or = 0.582, P
      < or = .05). Constant's reported corrections for age reduced (from r = -0.582 to
      r = -0.250, P < .05) but did not eliminate age as a confounding variable.
      CONCLUSIONS: Correlations exist between shoulder outcome scales, but existing
      shoulder scales are not equivalent in their assessments of function; they contain
      redundant information and, in some cases, may reflect a patient's age better than
      his/her shoulder function. The utility of conversion equations is minimized as a
      result of low to moderate correlations between scales.

PMID- 15262654
TI  - Excessive humeral external rotation results in increased shoulder laxity.
AB  - BACKGROUND: The quantitative relationship between increased anterior shoulder
      laxity and increased humeral external rotation observed in throwers remains
      unclear. HYPOTHESIS: An elongated anterior capsule, especially the anterior band
      of the inferior glenohumeral ligament, produced by excessive humeral external
      rotation will result in increased anterior shoulder laxity and increased humeral
      external rotation. STUDY DESIGN: Controlled laboratory study. METHODS: Seven
      cadaveric shoulders were tested to measure the humeral rotational range of
      motion, glenohumeral translations, and length of the anterior band of the
      inferior glenohumeral ligament. Data were collected for the intact shoulders and
      after nondestructive stretching of 10%, 20%, and 30% beyond maximum humeral
      external rotation. RESULTS: Nondestructive excessive external rotational
      stretching resulted in a significant increase in superior (30%, 3.3 mm) and
      inferior (30%, 2.3 mm) length of the anterior band of the inferior glenohumeral
      ligament, external rotation (30%, 35 degrees), and anterior (30%, 2.4 mm),
      inferior (30%, 2.2 mm), and anterior-posterior (30%, 5.1 mm) translations. There
      were significant positive linear correlations between the length of the anterior
      band of the inferior glenohumeral ligament, external rotation, and anterior
      translation. CONCLUSIONS: Excessive humeral external rotation results in an
      elongation of the anterior band of the inferior glenohumeral ligament and an
      increase in anterior and inferior glenohumeral translations and humeral external
      rotation. CLINICAL RELEVANCE: Repetitive excessive humeral external rotation
      observed in throwers may be one of the biomechanical causes for increased
      shoulder laxity and increased humeral external rotation.

PMID- 15262655
TI  - Eccentric training of the gastrocnemius-soleus complex in chronic Achilles
      tendinopathy results in decreased tendon volume and intratendinous signal as
      evaluated by MRI.
AB  - BACKGROUND: Satisfactory treatment results have been reported after eccentric
      calf muscle strength training in patients with chronic Achilles tendinopathy.
      HYPOTHESIS: Magnetic resonance imaging may be a useful adjunct in the evaluation
      of the effect of 3 months of eccentric calf muscle strength training. STUDY
      DESIGN: Prospective cohort study. METHODS: Using magnetic resonance imaging, the
      Achilles tendons were investigated in 25 patients (16 men and 9 women) ranging in
      age from 28 to 70 years (median, 51 years) before and after training. Five
      different magnetic resonance imaging sequences were used. Tendon volume and mean
      intratendinous signal were calculated using a new seed-growing technique showing
      99.3% and 96.6% intraobserver reliability, respectively. The clinical outcome was
      categorized according to pain level and performance using a questionnaire
      completed by the patient. RESULTS: The eccentric training resulted in a 14%
      (mean) decrease of tendon volume measured on T1-weighted images, from 6.6 +/- 3.1
      cm3 to 5.8 +/- 2.3 cm3 (P < .05). The intratendinous signal in the symptomatic
      Achilles tendon measured on proton density-weighted images decreased 23% (mean),
      from 227 +/- 77 signal units to 170 +/- 83 signal units (P < .05). The gadolinium
      contrast agent-enhanced images did not add further value compared with other
      sequences. CLINICAL OUTCOME: The clinical outcome was categorized as excellent in
      10, good in 3, fair in 5, and poor in 8 patients. The Delta signal correlated
      significantly with the pain level (P < .05). CONCLUSIONS: Eccentric training
      resulted in decreased tendon volume and intratendinous signal and was correlated
      with an improved clinical outcome. Magnetic resonance imaging techniques can be
      used as an adjunct to clinical evaluation by monitoring morphologic effects in
      clinical treatment studies of Achilles tendinopathy.

PMID- 15262656
TI  - Arthroscopic thermal shrinkage for hypermobile lateral meniscus.
AB  - BACKGROUND: The posterior segment of the lateral meniscus is relatively mobile as
      compared with that of the medial meniscus; that is because of its characteristic
      anatomy. Abnormal mobility of the lateral meniscus with no obvious rupture can be
      an unusual cause of knee pain and locking during deep knee flexion. PURPOSE: To
      evaluate results for a small series of patients with hypermobile lateral
      meniscus, treated with thermal shrinkage of the supporting ligaments. STUDY
      DESIGN: Series of case reports. METHOD: Five patients with hypermobile lateral
      meniscus were identified out of 625 patients who underwent meniscus surgery over
      a 20-month period. Thermal energy was applied to the peripheral zone of the
      lateral meniscus until abnormal translation was reduced. The patients were
      followed up an average of 21 months after the surgery. RESULTS: In 4 patients, no
      recurrence of locking was encountered in the postoperative period. In 1 patient,
      locking was experienced again 3 months after surgery and meniscal repair was
      performed. CONCLUSIONS: Thermal shrinkage can be considered an appropriate
      treatment in place of subtotal meniscectomy or meniscal repair for hypermobility
      of the lateral meniscus.

PMID- 15262657
TI  - Internal coxa saltans (snapping hip) as a result of overtraining: a report of 3
      cases in professional athletes with a review of causes and the role of ultrasound
      in early diagnosis and management.

PMID- 15262658
TI  - Acute traumatic first-rib fracture in the contact athlete: a case report.

PMID- 15262659
TI  - Irreducible posterolateral knee dislocation associated with interposition of the
      vastus medialis.

PMID- 15262660
TI  - Anterior cruciate ligament reconstruction in osteogenesis imperfecta: a case
      report.

PMID- 15262661
TI  - Shoulder injuries in golf.
AB  - Although often perceived as a leisurely activity, golf can be a demanding sport,
      which can result in injury, usually from overuse and sometimes from poor
      technique. The shoulder is a commonly affected site, with the lead shoulder, or
      the left shoulder in the right-handed golfer, particularly vulnerable to injury.
      A thorough understanding of the biomechanics of the golf swing is helpful in
      diagnosing and managing these injuries. Common shoulder problems affecting
      golfers include subacromial impingement, acromioclavicular arthrosis, rotator
      cuff tear, glenohumeral instability, and glenohumeral arthrosis. Although the
      majority of patients with these disorders will respond to nonsurgical treatment,
      including rest and a structured program of physical therapy, further benefits can
      be obtained with subtle modifications of the golf swing. Those golfers who fail
      to respond to nonsurgical management can often return to competitive play with
      appropriate surgical treatment.

PMID- 15262662
TI  - Management of the helmeted athlete with suspected cervical spine injury.
AB  - Improper handling of an unstable neck injury may result in iatrogenic neurologic
      injury. A review of published evidence on cervical management in the helmeted
      athlete with a suspected spinal injury is discussed. The approach to the neck
      injured helmeted athlete and the algorithms for on-field and emergency department
      evaluations are reviewed. The characteristics of the fitted football helmet allow
      safe access for airway management, and helmets and shoulder pads should not be
      initially removed unless absolutely necessary. Prehospital and emergency
      personnel should be trained in the indications for removal and in proper helmet,
      shoulder pad, and facemask removal techniques. If required, both helmet and
      shoulder pads should be removed simultaneously. Radiographs with equipment in
      place may be inadequate, and the value of computed tomography and magnetic
      resonance imaging in these helmeted patients has been studied. If adequate films
      cannot be obtained with equipment in place, helmet and shoulder pads may need to
      be removed before radiographic clearance. A plan should be formulated to prepare
      for such unexpected clinical scenarios as cervical spine injuries, and skills
      should be practiced. Airway and cervical spine management in these helmeted
      athletes is an area of ongoing research.

PMID- 15262663
TI  - Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: It has been hypothesized that certain Mycoplasma species may cause
      Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain,
      fatigue, and cognitive symptoms, and that affected patients may benefit from
      doxycycline treatment. OBJECTIVE: To determine whether a 12-month course of
      doxycycline improves functional status in Gulf War veterans with GWVIs. DESIGN: A
      randomized, double-blind, placebo-controlled clinical trial with 12 months of
      treatment and 6 additional months of follow-up. SETTING: 26 U.S. Department of
      Veterans Affairs and 2 U.S. Department of Defense medical centers. PARTICIPANTS:
      491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the
      blood. INTERVENTION: Doxycycline, 200 mg, or matching placebo daily for 12
      months. MEASUREMENTS: The primary outcome was the proportion of participants who
      improved more than 7 units on the Physical Component Summary score of the
      Veterans Short Form-36 General Health Survey 12 months after randomization.
      Secondary outcomes were measures of pain, fatigue, and cognitive function and
      change in positivity for Mycoplasma species at 6, 12, and 18 months after
      randomization. RESULTS: No statistically significant differences were found
      between the doxycycline and placebo groups for the primary outcome measure (43 of
      238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8
      percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for
      secondary outcome measures at 1 year. In addition, possible differences in
      outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in
      the doxycycline group had a higher incidence of nausea and photosensitivity.
      LIMITATIONS: Adherence to treatment after 6 months was poor. CONCLUSION: Long
      term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

PMID- 15262664
TI  - The incidence of end-stage renal disease is increasing faster than the prevalence
      of chronic renal insufficiency.
AB  - BACKGROUND: The steady increase in end-stage renal disease (ESRD) incidence is a
      worldwide public health crisis. OBJECTIVE: To determine whether the increasing
      incidence of ESRD in the United States is preceded by increased prevalence of
      chronic renal insufficiency. DESIGN: Birth cohort analysis. SETTING: Nationally
      representative Second and Third National Health and Nutrition Examination Surveys
      (NHANES II [1976-1980] and III [1988-1994]) and nationally comprehensive U.S.
      Renal Data System registry. PATIENTS: Adults, 20 to 74 years of age, surveyed in
      NHANES II (midpoint, 1978) and NHANES III (midpoint, 1991), and adults, 25 to 79
      years of age, who developed ESRD in 1983 and 1996. MEASUREMENTS: Prevalent
      chronic renal insufficiency (estimated glomerular filtration rate, 15 to 59
      mL/min per 1.73 m2) and new ESRD cases. RESULTS: From 1978 to 1991, the number of
      adults age 20 to 74 years with chronic renal insufficiency increased from 2.6 to
      3.9 million, an increase in prevalence from 1970 to 2460 per 100 000 persons.
      However, the increased incidence of ESRD was even greater during this period. For
      every 1000 adults with chronic renal insufficiency in 1978, 9 new cases of ESRD
      developed in 1983, but every 1000 adults with chronic renal insufficiency in 1991
      produced 16 new cases of ESRD in 1996 (relative risk, 1.7 [95% CI, 1.1 to 2.7]).
      LIMITATIONS: We could not follow individual patients with chronic renal
      insufficiency for the development of ESRD, and we used estimated rather than
      measured glomerular filtration rate. CONCLUSIONS: During the period examined,
      growth in incident ESRD outpaced growth in prevalent chronic renal insufficiency,
      demonstrating that the ESRD epidemic in the United States is not merely a
      function of more cases of kidney disease. Future research should examine other
      potential contributors to ESRD growth, such as improved survival from nonrenal
      diseases and more liberal entry into treatment programs.

PMID- 15262665
TI  - Mortality rates in elderly patients who take different angiotensin-converting
      enzyme inhibitors after acute myocardial infarction: a class effect?
AB  - BACKGROUND: Several randomized, controlled trials show that angiotensin
      converting enzyme (ACE) inhibitors improve survival in patients who have had an
      acute myocardial infarction. However, existing data from trials do not address
      whether all ACE inhibitors benefit patients similarly. OBJECTIVE: To evaluate
      whether all ACE inhibitors are associated with similar mortality in patients 65
      years of age or older who have had an acute myocardial infarction. DESIGN:
      Retrospective cohort study that used linked hospital discharge and prescription
      databases containing information on 18 453 patients 65 years of age or older who
      were admitted for an acute myocardial infarction between 1 April 1996 and 31
      March 2000. SETTING: 109 hospitals in Quebec, Canada. PATIENTS: 7512 patients who
      filled a prescription for an ACE inhibitor within 30 days of discharge and who
      continued to receive the same drug for at least 1 year. MEASUREMENTS: The
      association between the specific drugs and clinical outcomes was measured by
      using Cox proportional hazards models, with adjustment for demographic, clinical,
      physician, and hospital variables and dosage categories, represented by time
      dependent variables. RESULTS: Enalapril, fosinopril, captopril, quinapril, and
      lisinopril were associated with higher mortality than was ramipril; the adjusted
      hazard ratios and 95% CIs were 1.47 (95% CI, 1.14 to 1.89), 1.71 (CI, 1.29 to
      2.25), 1.56 (CI, 1.13 to 2.15), 1.58 (CI, 1.10 to 2.82), and 1.28 (CI, 0.98 to
      1.67), respectively. The adjusted hazard ratio associated with perindopril was
      0.98 (CI, 0.60 to 1.60). LIMITATIONS: The administrative databases did not
      contain detailed clinical information, and unmeasured factors associated with a
      patient's risk for death may have influenced physicians' prescription choices.
      CONCLUSION: Survival benefits in the first year after acute myocardial infarction
      in patients 65 years of age or older seem to differ according to the specific ACE
      inhibitor prescribed. Ramipril was associated with lower mortality than most
      other ACE inhibitors.

PMID- 15262666
TI  - Brief communication: the relationship between having a living will and dying in
      place.
AB  - BACKGROUND: Living wills, a type of advance directive, are promoted as a way for
      patients to document preferences for life-sustaining treatments should they
      become incompetent. Previous research, however, has found that these documents do
      not guide decision making in the hospital. OBJECTIVE: To test the hypothesis that
      people with living wills are less likely to die in a hospital than in their
      residence before death. DESIGN: Secondary analysis of data from a nationally
      representative longitudinal study. SETTING: Publicly available data from the
      Asset and Health Dynamics Among the Oldest Old (AHEAD) study. PATIENTS: People
      older than 70 years of age living in the community in 1993 who died between 1993
      and 1995. MEASUREMENTS: Self-report and proxy informant interviews conducted in
      1993 and 1995. RESULTS: Having a living will was associated with lower
      probability of dying in a hospital for nursing home residents and people living
      in the community. For people living in the community, the probability of in
      hospital death decreased from 0.65 (95% CI, 0.58 to 0.71) to 0.52 (CI, 0.42 to
      0.62). For people living in nursing homes, the probability of in-hospital death
      decreased from 0.35 (CI, 0.23 to 0.49) to 0.13 (CI, 0.07 to 0.22). LIMITATIONS:
      Retrospective survey data do not contain detailed clinical information on whether
      the living will was consulted. CONCLUSION: Living wills are associated with dying
      in place rather than in a hospital. This implies that previous research examining
      only people who died in a hospital suffers from selection bias. During advance
      care planning, physicians should discuss patients' preferences for location of
      death.

PMID- 15262667
TI  - A three-part intervention to change the use of hormone replacement therapy in
      response to new evidence.
AB  - BACKGROUND: Slow adaptation of new information by providers may result in
      suboptimal care. OBJECTIVE: To evaluate changes in prescriptions for combination
      hormone replacement therapy (HRT) after a multicomponent intervention to deliver
      new information to patients and providers. DESIGN: Quasi-experimental study with
      multiple baselines. SETTING: Veterans Affairs Tennessee Valley Healthcare System
      (VA-TVHS). PATIENTS: Female veterans age 50 to 79 years who had a prescription
      filled at the VA-TVHS for combination HRT between 1 January 2002 and 1 July 2002.
      MEASUREMENTS: Discontinuation of HRT. INTERVENTION: A 3-part intervention
      consisted of 1) notifying patients who were using combination HRT of the results
      of the Women's Health Initiative study (patient education component), 2) sending
      all providers an e-mail with the Women's Health Initiative study results
      (provider education component), and 3) placing an electronic alert in each
      eligible patient's chart (provider care component). The alert asked providers to
      reevaluate the need for combination HRT. The intervention was implemented at
      different VA-TVHS sites in a stepwise fashion to differentiate intervention
      effect from media effect. Study follow-up continued through 31 December 2002.
      RESULTS: The total rate of discontinuation of combination HRT was 70.3% in 2002.
      The proportion of discontinuation from time of media release until intervention
      was 23.3%. After initiation of the intervention, an additional 43% of the
      original cohort discontinued use of HRT; this percentage represents a 59%
      relative decrease in HRT use among patients. After adjustment for time, the
      discontinuation rate per day was 4.9 times higher after the multifacted
      intervention than after the media release (95% CI, 1.8 to 13.1). LIMITATIONS: A
      true control group is lacking. CONCLUSION: A multifaceted approach in an
      integrated health care system with standardized methods of communication is an
      effective way to implement patient-centered, effective, and timely care with
      changing medical knowledge.

PMID- 15262668
TI  - Allergic to generics.
AB  - A 69-year-old woman with several medical problems believes that she is allergic
      to generic medications. She frequently conflicts with her long-time primary care
      physician, who, as required by the patient's insurance coverage, refuses to
      prescribe brand-name drugs when generic alternatives are available. This conflict
      intensifies to a crisis when the patient develops life-threatening problems and
      still will not take prescribed generic medications. The presentation of this real
      case is accompanied by a discussion of the ethical dilemmas of the patient's
      physician, who must weigh the interests of a patient who clings to beliefs that
      the physician thinks are unfounded against the interests of a just rationing
      program and the broader population it serves.

PMID- 15262669
TI  - Ethics in practice: managed care and the changing health care environment:
      medicine as a profession managed care ethics working group statement.
AB  - Cost pressures and changes in the health care environment pose ethical challenges
      and hard choices for patients, physicians, policymakers, and society. In 2000 and
      2001, the American College of Physicians, with the Harvard Pilgrim Health Care
      Ethics Program, convened a working group of stakeholders--patients, physicians,
      and managed care representatives, along with medical ethicists--to develop a
      statement of ethics for managed care. The group explored the impact of a changing
      health care environment on patient-physician relationships and how to best apply
      the principles of professionalism in this environment. The statement that emerged
      offers guidance on preserving the patient-clinician relationship, patient rights
      and responsibilities, confidentiality and privacy, resource allocation and
      stewardship, the obligation of health plans to foster an ethical environment for
      the delivery of care, and the clinician's responsibility to individual patients,
      the community, and the public health, among other issues.

PMID- 15262670
TI  - Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease.
AB  - BACKGROUND: Apolipoprotein E (apoE) genotypes play critical roles in lipid
      metabolism and are believed to influence risk for coronary heart disease (CHD).
      Despite many population studies, however, the impact of apoE polymorphism on risk
      for CHD remains uncertain. PURPOSE: To qualitatively and quantitatively assess
      the evidence regarding the relation of apoE polymorphism to CHD risk. DATA
      SOURCES: All relevant reports and references from original and review papers
      published from 1966 to January 2004. STUDY SELECTION: Predefined criteria were
      used to identify 48 relevant studies. DATA EXTRACTION: A summary database that
      contained variables of study design, study sample and ethnicity, sex, apoE
      genotypes, CHD end points, plasma lipid levels, and other CHD risk factors was
      developed. DATA SYNTHESIS: The authors qualitatively evaluated many potential
      sources of heterogeneity. To quantify the extent of heterogeneity and assess the
      consistency of apoE-CHD associations, stratified analyses were conducted using
      the classic random-effects model. To further incorporate uncertainty due to
      between-study variation, the pooled odds ratios (ORs) and 95% credible intervals
      (CrIs) were estimated by using a Bayesian hierarchical model. Finally, the
      robustness of the pooled estimates was tested in multiple sensitivity analyses.
      Compared with individuals with the epsilon3/3 genotype, carriers of the apoE
      epsilon4 allele had a 42% higher risk for CHD (OR, 1.42 [95% CrI, 1.26 to 1.61]).
      The epsilon2 allele had no significant association with CHD risk (OR, 0.98 [CrI,
      0.66 to 1.46]). LIMITATIONS: This meta-analysis did not include unpublished data
      or studies published in languages other than English. CONCLUSIONS: Inadequate
      statistical power, differences in geographic and ethnic background, allele
      frequency, sex, CHD phenotypes, study design, and potential gene-environment
      interactions may have contributed to the conflicting results of previous studies.
      The apoE epsilon4 allele is a significant risk factor for CHD.

PMID- 15262671
TI  - Evaluation and management of the cardiovascular patient embarking on air travel.
AB  - Almost 2 billion passengers embark on international and domestic air travel each
      year. An increasing number of travelers will have cardiovascular disease as the
      population continues to age and our ability to treat cardiac disease improves.
      Guidelines for safe air travel in this population vary and are supported by few
      concrete data from randomized trials. Although the overall risk for clinically
      significant myocardial ischemia and arrhythmia during flight seems to be low in
      the population with stable cardiovascular disease, certain groups may be at
      increased risk. In-flight venous thrombosis is an increasingly recognized
      potential complication of prolonged air travel. Travelers with cardiovascular
      disease may be at increased risk for venous thrombosis as a result of depressed
      ejection fraction or immobility. This case-based review describes the risks of
      air travel in a 65-year-old man with known cardiovascular disease. After
      reviewing the limited data on safe air travel after myocardial infarction and the
      common complications after both percutaneous intervention and coronary artery
      bypass grafting, we provide recommendations on safe air travel after myocardial
      infarction. We discuss the safety of both preflight screening and the in-flight
      environment with regard to pacemakers and implantable automatic defibrillators.
      We also review the literature on in-flight venous thrombosis and provide
      recommendations to prevent in-flight deep venous thrombosis.

PMID- 15262672
TI  - The long aftermath of the 1991 gulf war.

PMID- 15262673
TI  - Is improved survival a class effect of angiotensin-converting enzyme inhibitors?

PMID- 15262674
TI  - Advance directives: time to move on.

PMID- 15262675
TI  - Late sequelae of induced abortion.

PMID- 15262676
TI  - Late sequelae of induced abortion.

PMID- 15262677
TI  - Costs of false-positive cultures from central catheters.

PMID- 15262678
TI  - An "inexcusable" case of muscle rigidity and shortness of breath.

PMID- 15262679
TI  - Angiogenesis therapy moves beyond cancer.

PMID- 15262680
TI  - Summaries for patients. Can antibiotics cure Gulf War veterans' illnesses?

PMID- 15262681
TI  - Summaries for patients. Possible causes of the increasing incidence of end-stage
      renal disease.

PMID- 15262682
TI  - Summaries for patients. ACE inhibitors after heart attacks: varying effects?

PMID- 15262683
TI  - Summaries for patients. Do living wills affect the setting where people die in
      the United States?

PMID- 15262684
TI  - Summaries for patients. Reducing the prescription of hormone replacement therapy
      after the release of study results.

PMID- 15262685
TI  - Pathogenesis of hypertension.

PMID- 15262686
TI  - Successful treatment of epidermolysis bullosa pruriginosa with topical
      tacrolimus.

PMID- 15262687
TI  - Acute bullous eruption with compartment syndrome due to intravenous infiltration.

PMID- 15262689
TI  - The role of dermatologists: my view.

PMID- 15262690
TI  - Are patients with psoriasis susceptible to the classic risk factors for actinic
      keratoses?
AB  - BACKGROUND: An increased prevalence of benign solar damage (eg, facial wrinkles)
      but not neoplastic lesions was observed among patients with psoriasis who were
      exposed to Dead Sea climatotherapy compared with controls. OBJECTIVES: To compare
      the prevalence of actinic keratosis in psoriatic patients and controls and to
      assess whether known risk factors behave similarly in both groups. DESIGN:
      Multicenter cross-sectional study. SETTING: Dermatology clinics in 4
      participating Israeli hospitals and at a Dead Sea clinic. PARTICIPANTS: Adult
      subjects (n = 460) with plaque-type psoriasis were recruited from the Israel
      Psoriasis Association (volunteer sample) and from dermatology clinics
      (convenience sample). The control group (n = 738) consisted of
      nonimmunosuppressed patients attending these clinics for benign conditions
      unrelated to sun exposure, such as atopic or contact dermatitis. MAIN OUTCOME
      MEASURES: Prevalence and distribution of actinic keratoses and odds ratios
      associated with skin, hair, and eye color and propensity or history of sunburn
      adjusted for age, ethnicity, and sun exposure. RESULTS: Actinic keratoses were
      observed in 200 controls (27%) and 51 subjects (11%) (P<.001). This increased
      prevalence occurred in both sexes, participants aged 35 years or older, all
      ethnic groups, smokers, and nonsmokers. The anatomical distribution of lesions
      did not substantially differ between subjects and controls. In multivariate
      analysis, psoriasis conferred a protective effect (odds ratio, <1), as did dark
      skin, dark eyes, and a history of severe sunburn in childhood. However,
      significant interactions were observed between psoriasis and hair color as well
      as psoriasis and propensity to sunburn, whereby a linear association was observed
      for controls but not for patients with psoriasis. CONCLUSIONS: Psoriasis confers
      protection against actinic keratosis. Hair color and propensity to sunburn exert
      differential effects among psoriatic patients and controls.

PMID- 15262691
TI  - Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of
      actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical
      trial.
AB  - BACKGROUND: No long-term randomized controlled clinical trial has compared the
      efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications
      for the treatment of actinic keratosis. OBJECTIVE: To determine the 6-month
      outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery. DESIGN:
      Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical
      trial performed in community and academic outpatient clinics. PATIENTS: A total
      of 144 patients with 5 or more visible or palpable actinic keratoses on the face.
      INTERVENTIONS: Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the
      4-week follow-up visit, residual lesions were treated with cryosurgery. MAIN
      OUTCOME MEASURE: Reduction in facial actinic keratoses from baseline to 4 weeks
      and 6 months. RESULTS: At 4 weeks, mean actinic keratosis lesion count was
      reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group
      (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5%
      fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months,
      mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery
      group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly
      more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle
      plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001). CONCLUSIONS:
      A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly
      more effective in reducing patients' numbers of actinic keratosis lesions 6
      months after treatment than cryosurgery alone. The high occurrence rate of
      actinic keratosis lesions at 6 months suggests a need for follow-up.

PMID- 15262692
TI  - UV radiation, latitude, and melanoma in US Hispanics and blacks.
AB  - BACKGROUND: Little information exists on the epidemiology of melanoma and the
      role of solar radiation in the development of melanoma in pigmented populations.
      OBJECTIVE: To evaluate the relationship between exposure to solar radiation and
      the incidence of melanoma in US Hispanics and blacks. DESIGN: Population-based
      ecological study. SETTING: State cancer registries of New York, New Jersey,
      Illinois, California, Texas, and Florida. Subjects Patients with invasive
      melanoma recorded by cancer registries. MAIN OUTCOME MEASURES: We obtained age
      adjusted, race/ethnicity- and sex-specific incidence rates of melanoma from
      similar time periods from the 6 cancer registries. The incidence rates were
      correlated with the annual mean UV index and the latitude of residency. RESULTS:
      For both Hispanics and blacks, the incidence of melanoma was positively
      associated with the UV index and negatively associated with the latitude of
      residency. Statistically significant correlation between melanoma and the UV
      index (R = 0.93; P =.01) and latitude (R = -0.80; P =.05) was observed in black
      males. Hispanics and blacks have a significantly lower incidence of melanoma than
      whites, with blacks having the lowest rates of melanoma. CONCLUSIONS: Exposure to
      solar radiation appears to play a role in the development of melanoma in both
      Hispanics and blacks. Sun protection and melanoma risk education should be
      performed in these populations.

PMID- 15262693
TI  - Effects of a superpotent melanotropic peptide in combination with solar UV
      radiation on tanning of the skin in human volunteers.
AB  - OBJECTIVE: Three phase 1 clinical trials of a superpotent melanotropic peptide,
      melanotan-1 (MT-1, or [Nle(4)-D-Phe(7)]alpha-melanocyte-stimulating hormone) were
      performed to demonstrate safety for MT-1 therapy combined with UV-B light or
      sunlight. DESIGN: Open-label studies at 2 dose levels of MT-1 combined with small
      doses of UV-B to the neck or buttock or full sunlight to half of the back.
      SETTING: Dermatology clinics at the Arizona Health Sciences Center, Tucson.
      INTERVENTIONS: The first study randomized 4 subjects to MT-1 (0.08 mg/kg per day
      subcutaneously) and 4 subjects to injections of isotonic sodium chloride (9%)
      solution for 10 days, followed by neck irradiation with 3 times the minimal
      erythema dose (MED) of UV-B light. In the next study (n = 12), the MT-1 dosage
      was increased to 0.16 mg/kg per day for 10 days, with UV-B radiation (0.25-0.75
      MED) given to a buttock site for 5 days during (n = 7) or after (n = 5) MT-1
      administration. A final study randomized 8 subjects to 3 to 5 days of sunlight to
      half of the back or to sunlight plus 0.16 mg/kg of MT-1 for 5 days per week for 4
      weeks. RESULTS: Tanning in the first study was achieved in 3 of 4 subjects
      receiving MT-1, and these subjects also had 47% fewer sunburn cells at the
      irradiated neck site. More skin sites darkened with the higher dose of MT-1 in
      the second study. In the third study, there was significantly enhanced tanning of
      the back in the MT-1 group, and this was maintained at least 3 weeks longer than
      the tanning in the sunlight-only controls, who required 50% more sun-exposure
      time for equivalent tanning. MAIN OUTCOME MEASURE: There were no pathologic
      findings at any UV-B or sun-exposed sites in any subject. Toxic effects due to MT
      1 were minor, consisting of nausea and transient facial flushing. CONCLUSION:
      Melanotan-1 can be safely combined with UV-B light or sunlight and appears to act
      synergistically in the tanning response to light.

PMID- 15262694
TI  - Nonmelanoma skin cancer mortality (1988-2000): the Rhode Island follow-back
      study.
AB  - OBJECTIVES: To estimate (1) the magnitude of and the components and factors
      associated with nonmelanoma skin cancer (NMSC) mortality and (2) the proportion
      of deaths misclassified as NMSC. DESIGN: Population-based follow-back study.
      SETTING AND PATIENTS: All Rhode Island residents whose deaths between 1988 and
      2000 were attributed to NMSC. MAIN OUTCOME MEASURES: Distribution of diagnoses,
      verification of the causes of death, and characterization of associated factors.
      RESULTS: The proportion of misclassified deaths was significantly higher for
      nongenital NMSC (57%) than for genital NMSC (18%; P<.001). Most of the deaths
      misclassified as nongenital NMSC were caused by squamous cell carcinoma of
      mucosal surfaces. The age-adjusted NMSC mortality rate was 0.91 (per 100 000
      persons per year), of which almost half (0.45) were due to genital carcinoma.
      Nonmelanoma skin cancer mortality increased sharply with age. The mortality rate
      from nongenital NMSC in men was more than twice that in women, but for genital
      NMSC this ratio was reversed. Skin cancers originating on the ear were
      responsible for more than a quarter of all deaths caused by nongenital NMSC. No
      cases of NMSC mortality occurred in organ transplant recipients. Many individuals
      had comorbid psychiatric conditions or evidence of unreasonable delay in seeking
      medical care for their lesions. CONCLUSIONS: Misclassifying the cause of death as
      nongenital NMSC accounts for a large source of error on death certificates in
      Rhode Island. Overall, nongenital squamous cell carcinoma and basal cell
      carcinoma death rates have declined, and mortality due to genital carcinoma was
      about half of total NMSC deaths. The dermatology community should emphasize
      prevention of mortality from genital skin cancer, while continuing to stress the
      importance of reducing excessive exposure to UV light and prompt treatment of
      NMSC.

PMID- 15262695
TI  - Thalidomide treatment for prurigo nodularis in human immunodeficiency virus
      infected subjects: efficacy and risk of neuropathy.
AB  - OBJECTIVE: To evaluate safety and efficacy of thalidomide in the treatment of
      prurigo nodularis in a group of human immunodeficiency virus (HIV)-infected
      patients whose condition was recalcitrant to standard treatment. DESIGN:
      Prospective study. SETTING: Outpatient dermatology and neurology clinic, both
      referral settings. PATIENTS: Eight HIV-infected patients with refractory prurigo
      nodularis; a total of 10 met inclusion criteria, but 2 could not be followed up.
      INTERVENTIONS: Treatment with thalidomide, 100 mg/d. Subjects were randomized
      after 1 month to receive 100 or 200 mg/d. If side effects were noted, the drug
      was reduced to a tolerable dose or discontinued. Subjects were monitored at
      baseline and monthly for degree of pruritus and total area of body involvement of
      prurigo nodularis. Sequential neurologic assessments were performed. MAIN OUTCOME
      MEASURES: Efficacy and toxic effects. RESULTS: The dosage of thalidomide ranged
      from 33 to 200 mg/d. Eight subjects had a greater than 50% response in reduction
      of itch over 3.4 months (average). Seven subjects had a greater than 50%
      reduction of skin involvement over 5 months (average). Three subjects developed
      thalidomide peripheral neuropathy (TPN). There was no correlation between
      duration of treatment, daily or cumulative dose, and TPN. A change in the
      Neuropathy Impairment Score of 10 points was a good marker of TPN, as was a
      greater than 50% decrease in the sural sensory nerve action potential amplitude.
      CONCLUSIONS: Thalidomide reduced the signs and symptoms of prurigo nodularis in
      HIV-infected subjects. One third of subjects developed TPN, underscoring the
      importance of careful neurologic assessment.

PMID- 15262698
TI  - Evaluation of sexual function with an international index of erectile function in
      subjects taking finasteride for androgenetic alopecia.
AB  - OBJECTIVE: To evaluate variations in sexual and erectile function in subjects
      taking 1 mg of finasteride for androgenetic alopecia by administering the
      abridged 5-item version of the International Index of Erectile Function (IIEF-5)
      questionnaire before and during treatment. DESIGN: In a multicenter study, 186
      patients with androgenetic alopecia were asked to complete the IIEF-5 regarding
      the domain of erectile function before (at baseline) and 4 to 6 months after
      beginning finasteride treatment. The test was self-administered. SETTING: The
      study was conducted in 7 institutional dermatology departments in Italy (Bologna,
      Rome, Genoa, Cagliari, Milan, Florence, and Bari). PATIENTS: A total of 186
      patients with androgenetic alopecia were evaluated before and 4 to 6 months after
      the initiation of finasteride therapy (1 mg). All patients (age range, 19-43
      years; mean age, 28.3 years) were followed up as outpatients. RESULTS: The score
      on each of the 5 domains of the IIEF-5 did not show any significant change after
      4 to 6 months of treatment. CONCLUSIONS: Our results support the clinical
      impression that sexual side effects are actually much less common than reported
      in clinical trials. The sexual function of all patients remained stable during
      treatment with 1 mg of finasteride.

PMID- 15262699
TI  - Poor prognosis of arthritis-associated pyoderma gangrenosum.
AB  - BACKGROUND: The association between pyoderma gangrenosum (PG) and arthritis is
      well established. We have observed a refractory population of patients with
      arthritis-associated PG (PGA). We, therefore, tested the hypothesis that
      differences exist in response to treatment in patients with PGA compared with
      patients with PG without arthritis. OBSERVATIONS: We performed a review of
      patients with PG during a 2-year period. Patients had noninfectious chronic
      ulcerations clinically typical for PG, exclusion of relevant differential
      diagnoses, and consistent histopathological features. Outcomes compared between
      patients with arthritis (PGA) and without arthritis (PG) included complete
      healing, percentage change in wound size, and duration of therapy. Of 10 PG
      ulcers, 7 healed, compared with 2 of 8 PGA ulcers. There was a greater mean
      percentage decrease in wound size in the PG vs the PGA ulcers (78.9% vs 23.4%; P
      =.10) and a shorter mean duration of treatment (8.7 vs 14.8 months; P =.18).
      CONCLUSIONS: The ulcers of patients with PGA seem more refractory to treatment
      than the ulcers of patients with PG alone. Those with PGA ulcers represent a
      refractory subset of patients, and the ulcers are possibly secondary to unique
      pathophysiological features.

PMID- 15262696
TI  - Hair and sweat glands in families with hypohidrotic ectodermal dysplasia: further
      characterization.
AB  - OBJECTIVES: To gather and compare clinical and histologic information from
      individuals affected by hypohidrotic ectodermal dysplasia (HED) and unaffected
      control subjects and to assess the value of these data in the diagnosis of HED.
      DESIGN: Volunteer subjects attending the 20th Annual Family Conference of the
      National Foundation for Ectodermal Dysplasia answered a questionnaire and
      performed a starch-iodide sweat-function test. A subset of the subjects also
      donated samples of hair and 4-mm punch biopsy specimens of palmar and scalp skin.
      Specimens from each of these tests were assessed in a blinded fashion. Analysis
      was performed comparing affected and control subjects for each of the following
      parameters: quantification of eccrine structures in the skin biopsy specimens,
      analysis of hair sample trichograms for hair shaft defects, and qualitative
      classification of starch-iodide palm-print sweat-function test results. SETTING:
      An international conference for families and individuals with ectodermal
      dysplasias. SUBJECTS: A total of 40 subjects were included in the final analysis:
      15 unaffected control subjects and 25 subjects with HED. Nine affected subjects
      and 9 unaffected subjects donated skin biopsy specimens. MAIN OUTCOME MEASURE:
      This study was designed to assess the value of 4 simple tests in supporting the
      diagnosis of HED. RESULTS: Investigators were blinded to group during analysis of
      the test samples. Trichogram examination identified 3 hair shaft abnormalities,
      with a slightly higher prevalence in the affected group: variable shaft
      thickness, trichorrhexis nodosa, and pili torti. The sensitivity and specificity
      for each of these findings was less than 40%. Starch-iodide paper palm imprints
      identified a higher likelihood of diminished or absent sweat in the affected
      group, but this test had a low sensitivity (44%) and an imperfect specificity
      (93%). Examination of horizontally sectioned skin biopsy specimens from the palm
      were devoid of eccrine structures in a minority of affected subjects
      (sensitivity, 30%; specificity, 100%). In contrast, scalp biopsy specimens lacked
      eccrine structures in the majority of affected subjects (sensitivity, 67%;
      specificity, 100%). Separate analysis excluding the subjects without apparent
      eccrine apparatus yielded comparable numbers of eccrine ducts from control and
      affected groups. CONCLUSIONS: We have defined the value of simple, easily
      performed tests in the morphological diagnosis of HED. Noninvasive trichogram and
      sweat testing results can support the diagnosis of HED, but they are not
      sensitive or highly specific; horizontally sectioned 4-mm punch biopsy specimens
      of the scalp or palms that lack eccrine structures are diagnostic of HED; scalp
      biopsy is much more sensitive than palmar biopsy; and a scalp biopsy specimen
      with detectable eccrine structures suggests that a patient does not have HED.

PMID- 15262700
TI  - Response of ulcerated perineal hemangiomas of infancy to becaplermin gel, a
      recombinant human platelet-derived growth factor.
AB  - BACKGROUND: Hemangiomas of infancy are the most common tumors of childhood, and
      ulceration is the most common complication. Many treatments have been used for
      hemangioma ulceration, although none are uniformly effective. A recent report
      described the successful use of 0.01% becaplermin gel, a recombinant human
      platelet-derived growth factor, for an ulcerated hemangioma refractory to
      standard care. We sought to further assess the responsiveness of hemangioma
      ulceration to 0.01% becaplermin gel and to compare its cost to that of
      conventional modalities. OBSERVATIONS: We report a case series of 8 infants
      treated with becaplermin gel for ulcerated perineal hemangiomas of infancy. All
      infants were seen between January and June 2003 in the pediatric dermatology
      clinic at Texas Children's Hospital. Six female and 2 male infants were included.
      All of the hemangiomas were large (> or =6 cm(2)), and of superficial or mixed
      superficial and deep morphology. Rapid ulcer healing occurred in all patients
      within 3 to 21 days (average, 10.25 days). CONCLUSIONS: In this small series,
      0.01% becaplermin gel was a safe and effective treatment for perineal hemangioma
      ulceration. The rapid healing achieved with 0.01% becaplermin gel allows a
      reduction in the risk of secondary infection, pain, and need for hospitalization,
      as well as in the costs that often accumulate from multiple follow-up visits and
      long-term therapy.

PMID- 15262701
TI  - The skin cancer paradox of psoriasis: a matter of life and death decisions in the
      epidermis.

PMID- 15262702
TI  - Multiple skin necrotic lesions.

PMID- 15262703
TI  - Chronic penile ulceration in a 72-year-old man.

PMID- 15262704
TI  - Perianal ulcer in a patient with AIDS.

PMID- 15262705
TI  - Progressive diffuse papules in a child..

PMID- 15262706
TI  - Dear dermatology applicant.

PMID- 15262707
TI  - The co-occurrence of ocular and cutaneous melanomas.

PMID- 15262708
TI  - Finasteride (Propecia) and the promotion of high-grade prostate cancer.

PMID- 15262709
TI  - Sun protection effect of dihydroxyacetone.

PMID- 15262710
TI  - An outbreak of Vibrio vulnificus infection in Kumamoto, Japan, 2001.

PMID- 15262711
TI  - Localized pemphigus foliaceus induced by topical imiquimod treatment.

PMID- 15262712
TI  - Use of SCORTEN to accurately predict mortality in patients with toxic epidermal
      necrolysis in the United States.

PMID- 15262713
TI  - Prevalence of alternative medicine use for skin conditions in a primary care
      population.

PMID- 15262714
TI  - Dermoscopy of melanocytic neoplasms: combined blue nevi.

PMID- 15262715
TI  - Forehead flap periorbital reconstruction.
AB  - OBJECTIVE: To evaluate functional and aesthetic results of periorbital defect
      repair using forehead flaps. DESIGN: Retrospective review of patients who
      received periorbital defect repair by 3 of us with a paramedian forehead flap
      alone or in conjunction with other local or regional flaps, bone grafts, or
      cartilage grafts. Flap survival, functional results, and postoperative
      complications were determined by physical examination at regular follow-up. Three
      experienced surgeons other than us quantified aesthetic outcomes using a 10-cm
      visual analog scale. RESULTS: Eighteen patients underwent periorbital defect
      repair between August 1, 1989, and December 31, 2000. Defects ranged from 8 to
      300 cm(2) (mean, 46.8 cm(2)) in area. The most commonly involved primary
      structures were the medial canthus, lacrimal drainage system, and medial upper
      eyelid. The mean improvement on a 10-cm visual analog scale was 1.6 from before
      resection to after reconstruction and 3.8 from tumor resection to after
      reconstruction. In all relevant cases, globe coverage and lacrimal drainage
      system patency were excellent. No patients experienced fistula formation or
      eyelid retraction. CONCLUSION: The reliability, versatility, and relative
      technical simplicity of the forehead flap provide excellent cosmetic and
      functional results in reconstruction of intermediate-sized periorbital defects,
      especially those associated with nasal defects.

PMID- 15262716
TI  - Baiting the cross-face nerve graft with temporary hypoglossal hookup.
AB  - BACKGROUND: Cross-face nerve grafting yields inconsistent neural regeneration,
      and methods that promote more robust axonal traversing of the graft would expand
      the indications for this procedure. OBJECTIVE: To test the hypothesis that
      hooking a cross-face nerve graft distally to a source of denervated muscle,
      rather than leaving it in the subcutaneous space, would positively affect neural
      ingrowth across the graft, based on elaboration of neurotrophins from the
      musculature. METHODS: Twenty-four rats underwent cross-face nerve grafting in
      which the right facial nerve buccal branch was transected and coapted to the
      graft. The graft was placed across the neck and into the left side of the face.
      The distal end of the graft was placed either in the left subcutaneous space,
      coapted to the marginal mandibular branch of the left facial nerve, or coapted to
      the distal stump of the transected left hypoglossal nerve. Eight control animals
      underwent right buccal branch transection and placement of a cross-face nerve
      graft without any proximal and distal hookup. After 12 weeks, all experimental
      groups underwent hookup of the distal nerve graft to the left facial nerve buccal
      branch. Vibrissal function was assessed during the ensuing 12 weeks, and then the
      graft was harvested for histomorphometric analysis. RESULTS: After 12 weeks,
      there was a significant difference in axon counts between the group coapted
      distally to the tongue (hypoglossal hookup) and that coapted to the facial
      musculature (marginal hookup). Twelve weeks later, after distal cross-face nerve
      graft hookup, this difference was not statistically significant, although the
      hypoglossally baited group demonstrated statistically significantly greater fiber
      maturity. Recovery of vibrissal movement did not differ among treatment groups.
      CONCLUSION: Baiting the cross-face nerve graft via temporary hookup to the distal
      hypoglossal nerve and tongue musculature appears to improve nerve ingrowth
      through a nerve graft across the face, although a corresponding improvement in
      facial muscle function was not observed.

PMID- 15262717
TI  - Evaluation of the Radiance FN soft tissue filler for facial soft tissue
      augmentation.
AB  - OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of Radiance
      FN (fine needle) (BioForm Inc, Franksville, Wis), a highly biocompatible, calcium
      hydroxylapatite-based implant, when used for facial soft tissue augmentation.
      METHODS: Ninety patients aged between 25 and 85 years underwent subdermal
      injection with Radiance FN. The primary areas treated were lips, nasolabial
      folds, glabellar rhytids, marionette lines, prejowl depressions, acne scars, and
      surgical soft tissue defects. Patients were surveyed after treatment and for up
      to 6 months for pain, ecchymosis, skin erythema, nodules, softness, appearance,
      and satisfaction. RESULTS: In terms of efficacy, at 6 months, appearance,
      softness, and overall patient satisfaction were rated good or excellent in 74%,
      80%, and 88% of patients, respectively. Moderate or severe pain occurred with
      injection in 59% of patients but disappeared 2 to 5 minutes after injection.
      Erythema, edema, and ecchymosis were common immediately after treatment but
      resolved in all patients within 2 weeks. Seven patients had persistent visible
      mucosal lip nodules, 4 of whom required intervention. CONCLUSIONS: Radiance FN is
      highly effective and well tolerated when used for facial soft tissue
      augmentation. Additional experience with longer follow-up will help determine the
      most appropriate use and long-term safety for the implant.

PMID- 15262718
TI  - Computed tomography technique for evaluation of the nasal valve.
AB  - OBJECTIVE: To compare measurements of the nasal valve on computed tomographic
      images obtained in the traditional coronal imaging plane with those obtained
      using the Nasal Base View (NBV) for evaluation of the sinonasal cavities.
      METHODS: Thirty computed tomograms of the sinuses were evaluated retrospectively.
      Coronal re-formations were performed in a plane perpendicular to the hard palate
      at the most anterior aspect of the nasal bones at the nasal dorsum. Re-formations
      of the NBVwere performed in a plane perpendicular to the anterior aspect of the
      estimated acoustic axis. Measurements of the nasal valve angle were performed for
      both imaging planes in each patient. RESULTS: Nasal valve angles measured in the
      traditional, coronal plane were found to have an angle of 8.3 degrees +/- 2.0
      degrees (mean +/- SD). Nasal valve angles measured in the NBV had an angle of
      11.4 degrees +/- 2.6 degrees. A significant difference was demonstrated (P<.001).
      CONCLUSIONS: The traditional coronal computed tomograms of the sinonasal cavities
      may underestimate the true nasal valve angle. The NBV may provide a more accurate
      assessment of the nasal valve, as the measured angles of the nasal valve in this
      plane were found to be more consistent with classic descriptions of 10 degrees to
      15 degrees.

PMID- 15262719
TI  - The Korean American woman's face: anthropometric measurements and quantitative
      analysis of facial aesthetics.
AB  - OBJECTIVES: To assess the differences in facial proportions between Korean
      American (KA) women and North American white (NAW) women and to quantitatively
      describe aesthetic facial features in the KA women. DESIGN: Anthropometric survey
      and facial aesthetic evaluation. PARTICIPANTS: Volunteer sample of KA women (n =
      72) who served as models for part 1 of the study and a different sample of KA
      women (n = 5) and men (n = 5) who served as judges for part 2 of the study. All
      subjects were between ages 18 and 35 years and had Korean parents and no previous
      facial surgery or trauma. Intervention For part 1 of the study, standardized and
      referenced frontal and lateral photographs were taken of the models, and 26
      standard anthropometric measurements were determined. Results were compared with
      published NAW standards. For part 2 of the study, 10 judges evaluated frontal
      views of the models for facial aesthetics using a visual analog scale.
      Quantitative analysis was done of the faces of attractive KA women (>90th
      percentile in aesthetic scores) and comparisons were made with the faces of NAW
      women and average KA women. RESULTS: The KA woman's face did not fit the
      neoclassical facial canons. Compared with NAW women, 24 of the 26 facial
      measurements in KA women were significantly different. Only 9 of the 26 facial
      measurements were significantly different when the attractive KA women were
      compared with the NAW women. Nine of the 17 nonsignificant facial measurements
      were very similar to those of the NAW women; many of these facial features
      centered around the midface. CONCLUSIONS: Although the average KA woman's facial
      anthropometric measurements were very different from those of the NAW woman,
      attractive KA women reflected many of the facial features of NAW women. These
      findings support the need for ethnically sensitive facial canons and further
      research into transcultural aesthetics.

PMID- 15262720
TI  - A validated rating scale for hyperkinetic facial lines.
AB  - OBJECTIVE: To test the reliability of a simple rating system to describe
      hyperkinetic facial lines. METHODS: A rated numeric kinetic line scale was
      developed and presented to 11 postresidency physicians specializing in aesthetic
      facial care. These physicians independently reviewed photographs of 20 patients,
      first at rest, then with activation of the frontalis, corrugator, and orbicularis
      oculi muscles. Kappa statistics for multiple raters were used to assess
      interobserver reliability. RESULTS: The nonweighted kappa values were between 0.4
      and 0.8 for the frontalis, corrugator, and orbicularis muscle groups. This
      represents moderate to substantial observer agreement and is highly significant
      for each muscle group. CONCLUSIONS: A new rating scale for hyperkinetic facial
      lines accounts for facial appearance at rest and with expression. It is easily
      used and has interobserver reliability. As the only objective and validated scale
      for hyperkinetic facial lines, this rated numeric kinetic line scale is
      recommended for the evaluation of pretreatment and posttreatment results in
      patients undergoing therapy for this problem. Moreover, an alternative scale
      rating resting and kinetic lines as independent variables is also being
      developed. Both must be considered to evaluate treatment outcomes when using
      neurotoxins.

PMID- 15262721
TI  - The ideal nasal profile: rhinoplasty patients vs the general public.
AB  - OBJECTIVES: To evaluate whether patients seeking reduction rhinoplasty hold a
      different concept of the ideal nose than does the general public, and to
      determine what features characterize the ideal nasal profile. METHODS: Twenty
      seven patients seeking reduction rhinoplasty and 15 randomly selected members of
      the public evaluated a series of computer-manipulated photographic profiles using
      a pictorial visual analogue scale to rate their preferences for several
      variables. Center-scale images were created from mesh-warped ("morphed") computer
      averaging of 12 white women. Differences between the rhinoplasty group and the
      public group were then compared, as was each group's deviation from the center of
      the scale. RESULTS: Both groups preferred narrowly distributed differences from
      the "average" profile to a high degree of significance. No statistically
      significant difference was found between the ideal nasal profiles selected by the
      rhinoplasty group and the public group. CONCLUSIONS: Reduction rhinoplasty
      patients do not appear to have a different concept of the ideal nose than does
      the public at large. The ideal nose, as it pertains to the ideal white female
      profile, has characteristics that differ from a mathematically averaged nasal
      profile.

PMID- 15262722
TI  - New techniques for management of the crooked nose.
AB  - The crooked or twisted nose results from a complex deformity of the bony pyramid,
      the upper and lower cartilaginous vaults, and the septum and causes functional
      and aesthetic problems. The forces of scar contracture coupled with long-standing
      cartilage deformation may make the crooked nose resistant to conventional
      surgical intervention. The middle vault of the nose may exhibit deformities that
      are due to atrophy, deviations, and skewing in relationship to the other regions
      of the nose. We report a series of 79 cases of significantly crooked noses to
      highlight 5 techniques not widely discussed in the facial plastic surgery
      literature.

PMID- 15262723
TI  - Use of a dual-mode erbium:YAG laser for the surgical correction of rhinophyma.
AB  - Rhinophyma is a cosmetically deforming disorder characterized by nodular
      hypertrophy of the nasal soft tissue. Treatment of rhinophyma usually consists of
      laser ablation or surgical excision for correction of the associated tissue
      deformity. We describe 6 patients with mild to severe rhinophyma who were treated
      with a dual-mode erbium:YAG (Er:YAG) laser, which provides the advantages of
      controlled ablative energy for tissue reduction and excellent intraoperative
      hemostasis. Outcome measures included patient satisfaction, clinician observer
      ratings, and an assessment of complications, including scarring, pigment
      abnormalities, and postoperative bleeding. All patients were satisfied with their
      outcomes, and no complications were detected during follow-up. All treatment
      outcomes were rated as very good to excellent at a 3-month follow-up visit. The
      flexibility of the dual-mode Er:YAG laser provides both controlled ablation and
      hemostasis, making it an ideal laser for the surgical treatment of rhinophyma.

PMID- 15262724
TI  - Comments on anatomy of the corrugator supercilii muscle.

PMID- 15262726
TI  - Giambattista Tiepolo's Young Lady in a Tricorn Hat.

PMID- 15262727
TI  - Genes for movement.

PMID- 15262728
TI  - Perspectives on shared genetic contributions for Parkinson disease and Alzheimer
      disease.

PMID- 15262729
TI  - Neurobiological bases of individual differences in emotional and stress
      responsiveness: high responders-low responders model.

PMID- 15262730
TI  - Anti-GQ1b ganglioside antibody in peripheral nervous system disorders:
      pathophysiologic role and clinical relevance.
AB  - The recent literature about autoimmune peripheral neuropathies has been dominated
      by the discovery of antibodies to a variety of glycosphingolipids. Gangliosides
      are important carbohydrate determinants for autoimmune activity, and several
      studies have suggested that serum antibodies against gangliosides are responsible
      for some forms of acute and chronic neuropathy syndromes. However, this view is
      disputable, and despite substantial progress in understanding the potential
      pathogenic effects of antiganglioside antibodies, many central issues remain
      unresolved across the whole pathogenic process. Miller Fisher syndrome has been
      classified as a variant of Guillain-Barre syndrome that comprises the clinical
      triad of ataxia, areflexia, and ophthalmoplegia. It has been considered the
      archetypal antiganglioside antibody-mediated human neuropathy because anti-GQ1b
      ganglioside antibody is detected in most patients with Miller Fisher syndrome,
      decays rapidly with clinical recovery, and is not found in normal and disease
      control serum samples. The only other case in which this antibody is found is in
      patients with related conditions, which might share the same pathogenic
      mechanism, such as Bickerstaff brainstem encephalitis. The strength of this close
      serologic-clinical association is such that measurement of anti-GQ1b antibody in
      suspected cases of Miller Fisher syndrome is a useful diagnostic marker for
      clinicians. This article reviews the occurrence, the pathophysiologic role, and
      the clinical background of anti-GQ1b ganglioside antibody in Miller Fisher
      syndrome and related disorders.

PMID- 15262731
TI  - Neuronal mechanisms of conscious awareness.

PMID- 15262732
TI  - Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic
      choreoathetosis.
AB  - BACKGROUND: Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks
      of involuntary movements that occur spontaneously while at rest and following
      caffeine or alcohol consumption. Previously, we and others identified a locus for
      autosomal dominant PDC on chromosome 2q33-2q35. OBJECTIVE: To identify the PDC
      gene. DESIGN: Analysis of PDC positional candidate genes by exon sequencing and
      reverse transcription-polymerase chain reaction. SETTING: Outpatient clinical and
      molecular genetic laboratory at a university hospital. Patients Affected (n = 12)
      and unaffected (n = 26) subjects from 2 unrelated families with PDC and 105
      unrelated control subjects. RESULTS: We identified missense mutations in the
      myofibrillogenesis regulator gene (MR-1) in affected subjects in 2 unrelated PDC
      kindreds. These mutations were absent in control subjects and caused
      substitutions of valine for alanine at amino acid positions 7 and 9. The
      substitutions disturb interspecies conserved residues and are predicted to alter
      the MR-1 gene's amino-terminal alpha helix. The MR-1 exon containing these
      mutations (exon 1) was expressed only in the brain, a finding that explains the
      brain-specific symptoms of subjects with these mutations. CONCLUSIONS: Although
      MR-1 gene function is unknown, the precedence of ion channel disturbance in other
      episodic neurologic disorders suggests that the pathophysiologic features of PDC
      also involve abnormal ion localization. The discovery that MR-1 mutations
      underlie PDC provides opportunities to explore this condition's pathophysiologic
      characteristics and may provide insight into the causes of other paroxysmal
      neurologic disorders as well as the neurophysiologic mechanisms of alcohol and
      caffeine, which frequently precipitate PDC attacks.

PMID- 15262733
TI  - Lack of familial aggregation of Parkinson disease and Alzheimer disease.
AB  - OBJECTIVE: To investigate the risk of Alzheimer disease (AD) in first-degree
      relatives of patients with Parkinson disease (PD) compared with first-degree
      relatives of controls. DESIGN: Case-control study, family history method, and
      reconstructed cohort approach. METHODS: Probands with PD without dementia and
      control probands, matched by age strata, sex, and ethnicity, were examined in
      person and enrolled without knowledge of family history of PD and other
      neurological disorders. Disease status in first-degree relatives of probands with
      PD and control probands was ascertained through a structured family history
      interview administered to the proband and a second informant (self-report or
      another informant). Cox proportional hazards models with double-censoring
      techniques for missing information on age of onset of AD were used to analyze the
      risk of AD in first-degree relatives of patients with PD compared with first
      degree relatives of controls. RESULTS: Four hundred eighty-seven probands with PD
      and 409 control probands provided family history information on 4819 first-degree
      relatives older than 30 years (2534 relatives of probands with PD and 2285
      relatives of control probands). One hundred thirteen first-degree relatives
      (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of
      controls) were diagnosed with AD. The risk of AD was not increased in relatives
      of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95%
      confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk
      of AD was observed when comparing relatives of patients with early-onset (< or
      =50 years) and late-onset (>50 years) PD with relatives of controls. CONCLUSION:
      The lack of familial aggregation of PD and AD does not support the hypothesis of
      major shared genetic contributions to the etiology of the 2 most common
      neurodegenerative disorders.

PMID- 15262735
TI  - Clustering of Parkinson disease: shared cause or coincidence?
AB  - BACKGROUND: The spatial and temporal pattern of excessive disease occurrence,
      termed clustering, may provide clues about the underlying etiology. OBJECTIVE: To
      report the occurrence of 3 clusters of Parkinson disease (PD) in Canada. DESIGN
      AND PATIENTS: We determined the population groups containing the clusters,
      geographical limits, and duration of exposure to the specific environments. We
      tested whether there was an excessive presence of Parkinson disease by
      calculating the probability of the observed cases occurring under the null
      hypothesis that the disease developed independently and at random in cluster
      subjects. Results of genetic testing for mutations in the alpha-synuclein,
      parkin, tau genes, and spinocerebellar ataxia genes (SCA2 and SCA3) were
      negative. RESULTS: The probabilities of random occurrence (P values) in the 3
      clusters were P = 7.9 x 10 (-7)for cluster 1, P = 2.6 x 10 (-7)for cluster 2, and
      P = 1.5 x 10 (-7)for cluster 3. CONCLUSIONS: Our findings indicate an important
      role for environmental causation in Parkinson disease. A possible role exists for
      environmental factors such as viral infection and toxins in the light of current
      evidence.

PMID- 15262734
TI  - Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year
      randomized controlled trial.
AB  - BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson
      disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole
      vs levodopa in early Parkinson disease, followed by levodopa supplementation,
      with respect to the development of dopaminergic motor complications, other
      adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter,
      parallel-group, double-blind, randomized controlled trial. SETTING: Academic
      movement disorders clinics at 22 sites in the United States and Canada. PATIENTS:
      Patients with early Parkinson disease (N = 301) who required dopaminergic therapy
      to treat emerging disability, enrolled between October 1996 and August 1997 and
      observed until August 2001. INTERVENTION: Subjects were randomly assigned to
      receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or
      25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n =
      150). Dosage was escalated during the first 10 weeks for patients with ongoing
      disability. Thereafter, investigators were permitted to add open-label levodopa
      or other antiparkinsonian medications to treat ongoing or emerging disability.
      MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic
      complications: wearing off, dyskinesias, on-off fluctuations, and freezing;
      changes in the Unified Parkinson's Disease Rating Scale and quality-of-life
      scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a
      significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard
      ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off
      (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa
      treatment resulted in a significant reduction in the risk of freezing (25.3% vs
      37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the
      occurrence of disabling dyskinesias was uncommon and did not significantly differ
      between the 2 groups. The mean improvement in the total Unified Parkinson's
      Disease Rating Scale score from baseline to 48 months was greater in the levodopa
      group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P
      =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more
      common in pramipexole-treated subjects than in levodopa-treated subjects. Mean
      changes in quality-of-life scores did not differ between the groups. CONCLUSIONS:
      Initial treatment with pramipexole resulted in lower incidences of dyskinesias
      and wearing off compared with initial treatment with levodopa. Initial treatment
      with levodopa resulted in lower incidences of freezing, somnolence, and edema and
      provided for better symptomatic control, as measured by the Unified Parkinson's
      Disease Rating Scale, compared with initial treatment with pramipexole. Both
      options resulted in similar quality of life. Levodopa and pramipexole both appear
      to be reasonable options as initial dopaminergic therapy for Parkinson disease,
      but they are associated with different efficacy and adverse-effect profiles.

PMID- 15262736
TI  - Prediction of hospital disposition after thrombolysis for acute ischemic stroke
      using the National Institutes of Health Stroke Scale.
AB  - BACKGROUND: Early determination of discharge destination after acute stroke may
      promote earlier rehabilitation and reduce costs by shortening the duration of
      hospitalization. OBJECTIVE: To determine whether the National Institutes of
      Health Stroke Scale (NIHSS) score predicts disposition in stroke patients treated
      with thrombolysis. DESIGN: Cohort study. SETTING: Academic and community
      hospitals from 3 countries. PATIENTS: Five hundred forty-six patients with acute
      ischemic stroke treated with recombinant tissue plasminogen activator (rt-PA).
      INTERVENTIONS: Medical records were reviewed for demographic information,
      vascular risk factors, location of stroke, initial NIHSS score, acute hospital
      disposition, and complications of symptomatic or asymptomatic intracerebral
      hemorrhage (ICH). MAIN OUTCOME MEASURE: Discharge destination to home, acute
      rehabilitation, or nursing facility. RESULTS: In multinomial regression analysis,
      increasing NIHSS score was a robust and independent predictor of discharge to
      rehabilitation or nursing facilities, roughly doubling for each 5-point
      increment. Patients who developed symptomatic ICH were never discharged to home,
      but asymptomatic ICH had no significant independent effect on disposition.
      CONCLUSIONS: Stroke severity as determined by the admission NIHSS score is the
      major independent predictor of disposition after hospitalization and treatment
      with rt-PA for acute stroke in a broad-based population. However, symptomatic ICH
      after rt-PA is a catastrophic event that may preclude discharge to home.

PMID- 15262737
TI  - Number needed to treat estimates incorporating effects over the entire range of
      clinical outcomes: novel derivation method and application to thrombolytic
      therapy for acute stroke.
AB  - BACKGROUND: Number needed to treat (NNT) is a useful measure of a treatment's
      clinical benefit or harm. However, NNT estimates for treatments for neurologic
      conditions have previously been generated only for dichotomized functional
      outcomes, which may underestimate clinically relevant treatment effects.
      OBJECTIVES: To develop a method for estimating NNTs for nonbinary outcomes from
      parallel design clinical trials and to illustrate its application to outcomes of
      fibrinolytic stroke therapy across the full range of the modified Rankin Scale
      (mRS) of disability. METHODS: Expert generation of joint distribution outcome
      tables in a model population affords a novel means to derive NNTs for nonbinary
      end points. Using mRS distributions from the National Institute of Neurological
      Disorders and Stroke-Tissue Plasminogen Activator trials, 10 neurologist and
      emergency physician acute stroke care experts independently specified the joint
      distribution of outcomes in model samples of 100 patients assigned to placebo and
      active therapy. RESULTS: The average estimated NNT for 1 additional patient to
      have a better outcome by 1 or more grades on the mRS as a result of treatment was
      3.1 (95% confidence interval, 2.6-3.6). The estimated number needed to harm was
      30.1 (95% confidence interval, 25.1-36.0). Expert estimates were robust across
      alternative stratifications of the mRS, with the NNT for benefit on 6- and 5-rank
      versions of 3.3 and 3.7 and the number needed to harm of 56.6 and 100.0,
      respectively. CONCLUSIONS: Expert generation of joint distribution outcome tables
      enables NNT estimation across a full spectrum of nonbinary outcomes. For every
      100 patients with acute stroke treated with tissue plasminogen activator,
      approximately 32 have a better final outcome and 3 have a worse final outcome as
      a result of treatment.

PMID- 15262738
TI  - Unitemporal vs bitemporal hypometabolism in mesial temporal lobe epilepsy.
AB  - BACKGROUND: Patients with mesial temporal lobe epilepsy (TLE) often show
      bilateral temporal hypometabolism (BTH), but the nature of this finding has not
      been well established. OBJECTIVE: To compare the clinical characteristics between
      unitemporal hypometabolism (UTH) and BTH patients in mesial TLE. DESIGN: Cross
      sectional study. SETTING: Epilepsy center at university hospital in Seoul, Korea.
      PATIENTS: We enrolled 95 patients with mesial TLE, 87 of whom had subsequently
      undergone surgery. Seizures, interictal and ictal electroencephalography (EEG),
      brain magnetic resonance imaging, Wada test, and neuropsychological test results
      were reviewed. (18)F-fluorodeoxyglucose positron emission tomography scans were
      interpreted visually. Patients were divided into 2 groups: UTH and BTH. RESULTS:
      There were 59 UTH patients and 36 BTH patients. Semiologic analysis showed that
      UTH patients had higher frequencies of aura and unilateral dystonic posturing,
      whereas BTH patients had higher frequencies of a nonlateralized bilateral ictal
      EEG pattern and bilateral interictal spikes. Moreover, BTH patients had more
      frequent symmetric Wada memory scores and white matter changes in the bilateral
      temporal lobes on brain magnetic resonance imaging than UTH patients. All UTH
      patients with bilateral TLE on scalp EEG showed unilateral seizure onset on
      intracranial EEG. CONCLUSIONS: The characteristic clinical findings of mesial TLE
      with BTH were a more frequent nonlateralized ictal EEG pattern, bitemporal
      interictal spikes, symmetric Wada memory score, and the anterior temporal white
      matter changes, and less frequent aura and unilateral dystonic posturing.
      Surgical outcomes were similar and good in both groups, although surgery could
      not be performed in 8 BTH patients (22%).

PMID- 15262739
TI  - Corpus callosum axonal injury in multiple sclerosis measured by proton magnetic
      resonance spectroscopic imaging.
AB  - BACKGROUND: Axonal damage has been observed in normal-appearing white matter
      (NAWM) for patients with multiple sclerosis (MS). OBJECTIVES: To investigate
      changes in brain metabolite ratios in a region of normal-appearing corpus
      callosum (CC) for patients with MS and to test its relationship to changes in
      other regions of NAWM. DESIGN AND METHODS: Data were collected from 24 patients
      with MS and 15 control subjects. Two-dimensional proton magnetic resonance
      spectroscopic imaging was performed centered at the CC. Regions of interest from
      normal-appearing CC were manually segmented using anatomical images. The NAWM
      outside the CC region was segmented based on the signal intensity in T1- and T2
      weighted images. RESULTS: The N-acetylaspartate-creatine-phosphocreatine ratio
      was lower in both regions for patients with secondary progressive MS compared
      with the controls; the N-acetylaspartate-creatine-phosphocreatine was lower only
      in the normal-appearing CC region for patients with relapsing-remitting MS
      (P<.001) compared with the controls. The ratio of choline-containing compound
      compared with the creatine-phosphocreatine ratio was also lower in the region of
      normal-appearing CC for patients with relapsing-remitting MS (P =.003) compared
      with the controls. There was a correlation between the N-acetylaspartate-creatine
      phosphocreatine ratio in the normal-appearing CC and T1 lesions (r = -0.53, P
      =.01) for all patients. CONCLUSIONS: The CC was a more sensitive location for
      depicting axonal injury than other regions of NAWM. A correlation between the
      reduction of the N-acetylaspartate-creatine-phosphocreatine ratio in the normal
      appearing CC and the T1 lesions may suggest that transection of axons in lesions
      may cause distant axonal damage and/or dysfunction that are expressed and more
      sensitively detectable in the CC.

PMID- 15262740
TI  - Digital video-electroencephalographic monitoring in the neurological
      neurosurgical intensive care unit: clinical features and outcome.
AB  - BACKGROUND: Prolonged electroencephalographic (EEG) recordings in the
      neurological-neurosurgical intensive care unit (NICU) may be performed in
      patients with status epilepticus, repetitive seizure activity, or an
      encephalopathy with or without seizures. The electroclinical correlation and
      neurological outcome of patients undergoing digital video-EEG monitoring (DVEEG)
      in the NICU has not been determined. OBJECTIVES: To evaluate the clinical utility
      and prognostic importance of the DVEEG in the NICU. METHODS: We retrospectively
      evaluated 105 patients who underwent DVEEG in the NICU at the Mayo Clinic,
      Rochester, Minn, between January 1, 1994, and July 31, 2001. All patients had a
      routine EEG recording performed prior to DVEEG. RESULTS: The mean age of the
      patients at the time of the DVEEG was 54 years (age range, 16-88 years). The mean
      duration of the DVEEG was 2.9 days (range, 1-17 days). Forty-four patients (42%)
      had a severe encephalopathy (Glasgow Coma Scale score, <8) at the time of the
      DVEEG. Forty-five patients (42.8%) had generalized convulsive status epilepticus,
      19 patients (18.1%) had nonconvulsive status epilepticus, and 7 patients (6.7%)
      had epilepsia partialis continua. The mean duration of follow-up was 7 months
      (range, 1-54 months). The outcome in 84 patients included death in 38 patients,
      severe neurological deficits, that is, bed bound and needs support for activities
      of daily living, in 6 patients, and a vegetative state in 3 patients. Fifteen
      individuals had no neurological impairment during follow-up. Refractory status
      epilepticus (P<.003), hypoxic-ischemic encephalopathy (P<.004), and multiple
      cerebral infarcts (P<.003) were the factors associated with increased mortality
      in univariate analysis. With multivariate logistic regression analysis only the
      presence of multiple strokes (P<.03; odds ratio, 5.62) was predictive of
      mortality. CONCLUSIONS: Continuous EEG monitoring is essential in the diagnosis
      and treatment of refractory status epilepticus or an encephalopathy with seizures
      in the NICU. A minority of these patients, however, experienced a favorable
      neurological outcome.

PMID- 15262741
TI  - Immunolocalization and activation of transcription factor nuclear factor kappa B
      in dysimmune neuropathies and familial amyloidotic polyneuropathy.
AB  - BACKGROUND: Recently, immunoreactivity of transcription factor nuclear factor
      kappaB (NF-kappaB) was found in peripheral nerves from patients with Guillain
      Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and
      familial amyloidotic polyneuropathy (FAP), suggesting a role in their
      pathogenesis. OBJECTIVE: To investigate expression and activation of NF-kappaB in
      nerve biopsy specimens from patients with peripheral neuropathies of different
      origins. PATIENTS: Nerve biopsies from 17 patients (5 with CIDP, 3 with
      vasculitis, 4 with Charcot-Marie-Tooth disease, and 5 with FAP) and 3 normal
      sural nerves were studied by immunocytochemistry and Western blot of nuclear
      extracts for the activated form of NF-kappaB. Nuclear factor kappaB DNA-binding
      activity was studied by electrophoretic mobility shift assay. RESULTS:
      Immunobinding for the activated form p65 of NF-kappaB was found in 2% to 5% of
      endoneurial vessel walls, in the external myelin of 5% to 10% of fibers, and in a
      few axons in CIDP specimens. It was also found in 5% to 15% of epineurial and
      endoneurial vessels in vasculitis specimens and at the level of amyloid deposits
      in FAP nerves. Nuclear factor kappaB immunoreactivity was not correlated to type
      of inflammatory cells, but it often corresponded to the deposition of the
      terminal complement complex C5b9. Western blot analysis of nuclear extracts
      showed a single band corresponding to 65 kDa in all affected nerves. Nuclear
      factor kappaB DNA-binding activity was revealed by electrophoretic mobility shift
      assay in specimens from patients with CIDP, vasculitis, and FAP. CONCLUSION: Our
      novel findings suggest a crucial role of NF-kappaB in inflammatory neuropathies
      and FAP.

PMID- 15262743
TI  - A new rare mutation (691delCC/insAAA) in exon 17 of the PYGM gene causing McArdle
      disease.
AB  - OBJECTIVE: To investigate the genetic effect of a new mutation found in exon 17
      of the myophosphorylase (PYGM) gene as a cause of McArdle disease (also known as
      type 5 glycogenosis). Patients A Spanish patient with McArdle disease was
      screened for 3 common mutations in the PYGM gene (R49X, W797R, and G204S), as
      previously described. The patient was heterozygous for R49X. To find other
      mutations, the coding sequence of the entire PYGM gene was sequenced. The carrier
      status of his relatives was also studied. RESULTS: A novel rare mutation was
      found in codon 691 of exon 17. This is an insertion/deletion (indel) and consists
      simultaneously of a deletion of 2 bases and an insertion of 3 bases
      (691delCC/insAAA). A restriction analysis was designed to simplify the detection
      method. CONCLUSIONS: The 691delCC/insAAA is the third indel described in the PYGM
      gene. Indels represent 0.95% of the total reported mutations in the Human Gene
      Mutation Database. The molecular origin of this mutation is not fully understood.
      These findings point again to the allelic heterogeneity of McArdle disease.

PMID- 15262742
TI  - Frontal assessment battery and differential diagnosis of frontotemporal dementia
      and Alzheimer disease.
AB  - BACKGROUND: The different distribution of pathologic features in frontotemporal
      dementia (FTD) and Alzheimer disease (AD) predicts a predominant dysexecutive
      syndrome in FTD. The Frontal Assessment Battery (FAB) has previously been
      validated in diseases associated with a frontal lobe dysfunction. OBJECTIVE: To
      evaluate the sensitivity of the FAB to differentiate FTD and AD. DESIGN:
      Comparison study. SETTING: Memory Clinic of the Salpetriere Hospital, Paris,
      France. PATIENTS: Twenty-six patients with FTD and 64 patients with AD. MAIN
      OUTCOME MEASURES: Comparison of FAB and Mini-Mental State Examination (MMSE)
      scores between patients with FTD and those with AD. RESULTS: The mean +/- SD FAB
      scores significantly differed between patients with FTD (7.6 +/- 4.2) and those
      with AD (12.6 +/- 3.7) (P<.001), but not MMSE scores. The FAB correctly
      identified 78.9% of the patients. These results were maintained in a subgroup of
      mildly demented patients (MMSE score, > or =24). In these patients, a cutoff
      score of 12 on the FAB was optimal to differentiate both disorders (sensitivity,
      77%; specificity, 87%). CONCLUSIONS: The FAB takes less than 10 minutes to
      administer and provides an objective measure to distinguish FTD from AD in mildly
      demented patients.

PMID- 15262744
TI  - Barbiturate withdrawal following Internet purchase of Fioricet.
AB  - BACKGROUND: The Internet enables businesses to advertise their pharmaceutical
      products and services without medical supervision. The Internet also allows for
      the unsupervised purchase of medications that may have neurologic consequences.
      OBJECTIVE: To describe acute withdrawal delirium following the abrupt
      discontinuation of Fioricet. PATIENT: The patient was a 37-year-old woman with a
      history of depression and migraine headaches but not drug abuse. She developed a
      florid withdrawal delirium following the discontinuation of a drug she purchased
      online. The medication, which contained butalbital, was self-administered in
      escalating doses for the treatment of chronic headaches. Daily doses of up to 750
      mg to 1000 mg were reported. RESULTS: The patient was admitted to the hospital
      for the treatment of unexplained seizures that were followed by several days of
      an intense withdrawal syndrome. Little improvement was noted after the
      administration of benzodiazepines and phenothiazine. After parenteral
      phenobarbital administration, her symptoms resolved. CONCLUSIONS: The withdrawal
      state from barbiturates is similar to that from ethanol. Tolerance can develop
      with prolonged abuse, leading to escalating drug doses to achieve the desired
      effect. The suggested management of both types of withdrawal syndromes is
      similar, but the relative resistance of the behavioral and autonomic features in
      patients was remarkable. Physicians should be aware of the ease with which
      medications can be purchased without supervision from Internet pharmacies. The
      magnitude of the number of drugs that are made available through this means
      creates a proclivity to withdrawal states.

PMID- 15262745
TI  - Ischemic stroke during sexual intercourse: a report of 4 cases in persons with
      patent foramen ovale.
AB  - BACKGROUND: The association between patent foramen ovale (PFO) and stroke risk in
      young adults is controversial and poorly understood. Paradoxical embolization
      through a PFO represents a possible mechanism by which PFO might predispose to
      stroke. OBJECTIVE: To describe 4 patients with PFO who experienced the onset of
      ischemic stroke during sexual intercourse. DESIGN: Case series. SETTING: Tertiary
      referral stroke clinic. PATIENTS: Consecutive patients experiencing stroke during
      intercourse. RESULTS: All 4 patients were found to have PFO. Despite a thorough
      evaluation, no other etiology for stroke was identified. CONCLUSION: We suggest
      that paradoxical embolization through a PFO due to elevated intrathoracic
      pressure during sexual activity could be a potential mechanism for stroke in
      these patients.

PMID- 15262746
TI  - Surgical treatment for mesial temporal lobe epilepsy in the presence of massive
      calcified neurocysticercosis.
AB  - BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic disease of the
      human central nervous system and a major health problem for most developing
      countries. The most common clinical manifestations of NCC are epileptic seizures.
      Whenever epilepsy and NCC coexist in the same patient, an uncertainty may rise
      about a causal relationship between them. OBSERVATION: We described a female
      patient with disseminated calcified NCC lesions and intractable epilepsy. Her
      medical history included cysticercotic meningoencephalitis and status epilepticus
      caused by active NCC. Fundoscopy showed the ocular presence of parasite; computed
      tomography of the brain showed evidence of cystic lesions with the scolex and
      calcified lesions; enzyme-linked immunosorbent assay of the cerebrospinal fluid
      was positive for cysticercosis. Epileptic seizures started after an 8-year silent
      period. Magnetic resonance imaging showed left hippocampal sclerosis. Plain x-ray
      film showed calcifications in muscles and subcutaneous tissue. Video
      electroencephalography and ictal and interictal single-photon emission computed
      tomography disclosed left mesial temporal lobe epilepsy. The patient underwent
      left temporal lobectomy and has been seizure free since surgery, for a follow-up
      of 4 years. CONCLUSION: This case report highlights and supports surgical therapy
      in patients with epileptic seizures and calcified NCC, even when there are
      several calcifications, provided that clear localization of epilepsy has been
      determined by means of a presurgical workup.

PMID- 15262747
TI  - Posttraumatic cerebrospinal fluid hypertension and hypotension.

PMID- 15262748
TI  - Sparganosis presenting as a conus medullaris lesion: case report and literature
      review of the spinal sparganosis.
AB  - BACKGROUND: Sparganosis is a rare parasitic infection affecting various organs,
      including the central nervous system. In rare cases, sparganosis may involve the
      spinal cord, usually at the thoracic area. We herein report, to our knowledge,
      the first case of sparganosis presenting as a conus medullaris lesion and review
      the literature of sparganosis involving the spinal cord. OBSERVATION: A 42-year
      old man presented with progressive perianal paresthesia and sphincter
      disturbances. Results of enzyme-linked immunosorbent assay of the cerebrospinal
      fluid and surgical biopsy were consistent with sparganum infection affecting the
      conus medullaris. We reviewed 7 other cases of spinal sparganosis. CONCLUSIONS:
      Sparganosis may present as a conus medullaris lesion. This possibility should be
      considered when clinicians encounter patients with a conus medullaris lesion or
      cauda equina syndrome with uncertain diagnosis.

PMID- 15262749
TI  - Transient ischemic attack and patent foramen ovale: evidence of paradoxical
      embolism.

PMID- 15262750
TI  - Spinal cord swelling in human T-lymphotropic virus 1-associated
      myelopathy/tropical spastic paraparesis: magnetic resonance indication for early
      anti-inflammatory treatment?

PMID- 15262751
TI  - Defecation-induced vertigo.

PMID- 15262752
TI  - Alfred Hauptmann, Siegfried Thannhauser, and an endangered muscular disorder.

PMID- 15262753
TI  - Postpolio syndrome.

PMID- 15262754
TI  - Pulsed intravenous methylprednisolone therapy in progressive multiple sclerosis:
      need for a controlled trial.

PMID- 15262755
TI  - Comparison of magnetic resonance imaging abnormalities in Japanese encephalitis
      and acute necrotizing encephalopathy of childhood.

PMID- 15262756
TI  - The anterolateral thigh flap: radial forearm's "big brother" for extensive soft
      tissue head and neck defects.
AB  - OBJECTIVE: The anterolateral thigh flap has recently been rediscovered in Asia as
      a perforator flap. The objective of this study was to describe the reliability
      and donor morbidity of the anterolateral thigh flap for head and neck
      reconstruction without transmuscular perforator dissection. DESIGN: Consecutive
      case series by a single surgeon. SETTING: A regional tertiary-referral head,
      neck, and skull base surgical oncology center. PATIENTS: The first 34 consecutive
      patients. INTERVENTION: Microvascular reconstruction with an anterolateral thigh
      free flap. MAIN OUTCOME MEASURES: Primary insufficiency, partial necrosis,
      complete necrosis, and donor morbidity rates. RESULTS: Two flaps necrosed
      partially (6%). No flaps demonstrated primary insufficiency, necrosed completely,
      or incurred significant donor morbidity. CONCLUSIONS: The anterolateral thigh
      flap can be reliably harvested without transmuscular perforator dissection and
      without incurring serious donor morbidity. It possesses workhorse attributes (no
      repositioning, remote from defect, long pedicle) and is extremely versatile (one
      is able to independently tailor the skin and muscle), making it ideal for the
      heterogeneous group of extensive soft tissue head and neck defects. When a
      forearm flap will likely be too thin or too morbid, the anterolateral thigh flap
      can be considered its "big brother."

PMID- 15262757
TI  - Management and outcome of recurrent well-differentiated thyroid carcinoma.
AB  - BACKGROUND: The AMES (age, distant metastasis, tumor extent, and size), AGES
      (age, tumor size, histologic grade, tumor extent, distant metastasis), and MACIS
      (distant metastasis, age, completeness of primary tumor resection, local
      invasion, and tumor size) prognostic systems for well-differentiated thyroid
      carcinoma (WDTC) are well known. The development of disease recurrence is
      associated with a poor outcome; however, the prognostic importance of multiple
      treatment failures has not been clearly reported. OBJECTIVES: To identify
      patient, tumor, and treatment factors that may be associated with the development
      of multiple recurrences in WDTC. DESIGN AND SETTING: All patients treated for
      residual or recurrent WDTC were retrospectively identified from the thyroid
      cancer database at the Department of Otolaryngology-Head and Neck Surgery, Mount
      Sinai Hospital, Toronto, Ontario (1963-2000). Data on relevant patient, tumor,
      and treatment factors were collected. MAIN OUTCOME MEASURES: Patient, tumor, and
      treatment factors predicting the development of multiple treatment failures,
      disease-specific survival, and overall survival. RESULTS: A total of 574 patients
      (115 male, 459 female; median age, 42 years [range, 9-92 years]) were identified,
      whose final histopathologic diagnosis was papillary carcinoma in 468, follicular
      carcinoma in 76, and mixed in 30 cases. TNM staging was as follows: 409 (71%)
      stage I, 66 (12%) stage II, 68 (12%) stage III, and 31 (5%) stage IV. Initial
      management included total thyroidectomy for 217 patients (38%), subtotal
      thyroidectomy for 357 (62%), and adjuvant iodine 131 therapy for 492 (86%).
      Seventy-three patients (13%) developed recurrent WDTC (21 male, 52 female; median
      age, 44 years [range, 18-84 years]). Patients were divided into 3 groups: group 1
      (no recurrence, n = 501), group 2 (1 recurrence only, n = 42), and group 3
      (multiple recurrences, n = 31). Group 2 data were as follows: site of recurrence
      (locoregional, 25; distant, 7; unspecified, 10) and treatment (surgery, 12;
      iodine 131, 42) and for group 3: site of first recurrence (locoregional, 16;
      distant, 11; unspecified, 4) and treatment (surgery, 14, iodine 131, 22;
      palliation, 1). Actuarial disease-specific survival at 20 years was 100%, 94%,
      and 60%, respectively, for the 3 groups (median follow-up, 7 years; range, 1-34
      years). Male sex, advanced stage, extrathyroidal spread, and primary treatment
      with total thyroidectomy were predictive factors for multiple recurrences on
      multivariate regression (all P<.05). CONCLUSIONS: Male sex, advanced initial
      stage, and presence of extrathyroidal spread within the primary tumor are the
      most significant independent predictors of developing multiple recurrences in
      patients with WDTC. These patients have a poor prognosis with a significant
      reduction in tumor-free survival.

PMID- 15262758
TI  - Clinical significance of health status assessment measures in head and neck
      cancer: what do quality-of-life scores mean?
AB  - OBJECTIVES: To determine the magnitude of clinically significant differences in
      domain scores for a quality-of-life questionnaire specific to head and neck
      cancer; and to demonstrate a clinically relevant method of presenting head and
      neck cancer-specific quality-of-life data using cutoff scores and clinical
      anchors. DESIGN: Anchor-based and distribution-based techniques for determining
      clinically significant differences in health-related quality-of-life scores were
      used. SETTING: University-based tertiary care hospital. PATIENTS: A total of 421
      patients with head and neck cancer enrolled in a longitudinal outcomes project.
      MAIN OUTCOME MEASURES: The Head and Neck Cancer Inventory; clinical anchor health
      status in the domains of speech, eating, and social disruption; and distribution
      based clinically significant score differences. RESULTS: Clinical anchor health
      states representing incremental levels of dysfunction were significantly
      correlated with domain scores for eating, speech, and social disruption. The
      anchor-based clinically important difference magnitudes were consistent with the
      values obtained using distribution-based techniques. For mean domain scores
      (minimum, 0; maximum, 100), differences of approximately 4, 10, and 14 or greater
      represented small, intermediate, and large clinically significant differences,
      respectively. Stratifying mean domain scores into low (0-30), intermediate (31
      69), and high (70-100) categories allowed presentation of the health-related
      quality-of-life data in a clinically relevant format. CONCLUSIONS: This study
      provides benchmarks for small, intermediate, and large clinically significant
      changes in scores and demonstrates the presentation of health-related quality-of
      life data in a clinically useful format.

PMID- 15262759
TI  - Decreased short- and long-term swallowing problems with altered radiotherapy
      dosing used in an organ-sparing protocol for advanced pharyngeal carcinoma.
AB  - OBJECTIVE: To determine the effect of a reduced radiotherapy dose on short- and
      long-term swallowing problems after organ-sparing treatment. DESIGN: Prospective
      case series. SETTING: Tertiary care referral center. PATIENTS: A consecutive
      sample of 29 patients with advanced oropharyngeal or hypopharyngeal cancer who
      were treated with intravenous hydroxyurea and concomitant hyperfractionated,
      accelerated radiotherapy. INTERVENTIONS: Initial experience with 74.4 Gy of
      radiation demonstrated severe long-term swallowing problems, prompting a dose
      reduction to 60.0 Gy. Eighteen patients were followed up for this study in the
      74.4-Gy group, while 11 were in the 60.0-Gy group. MAIN OUTCOME MEASURES:
      Swallowing variables were assessed in both patient groups at 4 months and at 12
      months following completion of therapy. RESULTS: Patient demographics and tumor
      characteristics were similar in each group, while significant differences were
      noted in the posttreatment clinical swallowing variables. Persistent severe
      odynophagia at 4 months (89% [16/18] vs 30% [3/10]) and at 12 months (64% [7/11]
      vs 11% [1/9]) was greater in the 74.4-Gy group (P =.002). Clinical signs of
      aspiration were also increased in the 74.4-Gy group, with 81% (13/16) vs 11%
      (1/9) at 4 months and 60% (6/10) vs 11% (1/9) at 12 months (P<.05). Most
      striking, however, was the incidence of long-term gastrostomy, with 78% (14/18)
      of patients receiving 74.4 Gy requiring gastrostomy feedings at 12 months
      compared with 18% (2/11) in the 60.0-Gy group (P =.002). Local control was
      unchanged by the altered dosing, with median follow-ups of 43.5 and 24.0 months
      in the 74.4-Gy and 60.0-Gy groups, respectively. CONCLUSION: Decreased radiation
      doses can maintain disease control and reduce treatment-related long-term
      swallowing complications.

PMID- 15262760
TI  - Diagnostic accuracy of magnetic resonance imaging in the assessment of mandibular
      involvement in oral-oropharyngeal squamous cell carcinoma: a prospective study.
AB  - OBJECTIVE: To evaluate the sensitivity, specificity, accuracy, and predictive
      values of magnetic resonance imaging (MRI) in the assessment of mandibular
      involvement in oral-oropharyngeal squamous cell carcinoma. DESIGN: Prospective
      study. SETTING: University hospital. PATIENTS: Forty-three patients with oral or
      oropharyngeal squamous cell carcinoma undergoing marginal or segmental
      mandibulectomy between January 1, 1994, and January 31, 2003. INTERVENTIONS:
      Indications for mandibulectomy were MRIs suggestive of bony invasion, tumor
      involving the retromolar trigone or the alveolar ridge, recurrent or persistent
      lesion, or intraoperative suspicion of periosteal invasion. Detection of tumor
      signal replacing the hypointense cortical rim was considered the main radiologic
      finding for mandibular invasion. MAIN OUTCOME MEASURES: The MRI findings were
      subsequently compared with histopathologic data of surgical specimens with
      reference to the presence of cortical and/or medullary mandibular involvement.
      RESULTS: Sixteen patients had MRI findings suggestive of mandibular involvement.
      Segmental mandibulectomy was performed in 15 cases and marginal resection in the
      remaining case. In 14 patients, bony invasion was confirmed. All of the other 27
      patients who underwent marginal or segmental mandibulectomy with negative MRI
      findings had no histopathologic evidence of mandibular involvement, except in 1
      patient: on histopathologic examination, despite cortical integrity, neoplastic
      vascular embolization into the bony lacunae was detected. Sensitivity of MRI in
      detecting mandibular involvement was 93%; specificity, 93%; accuracy, 93%; and
      negative and positive predictive values, 96% and 87.5%, respectively.
      CONCLUSIONS: Magnetic resonance imaging is commonly considered the technique of
      choice for treatment planning in advanced oral and oropharyngeal squamous cell
      carcinoma because of its accuracy in depicting soft-tissue involvement. This
      study demonstrates the additional diagnostic value of MRI in detecting bone
      invasion.

PMID- 15262761
TI  - Patterns of drainage and recurrence following sentinel lymph node biopsy for
      cutaneous melanoma of the head and neck.
AB  - OBJECTIVES: To analyze lymphatic drainage patterns and recurrence patterns in
      patients undergoing sentinel lymph node biopsy (SLNB) for cutaneous head and neck
      melanoma. DESIGN: Retrospective review of a consecutive series with a mean follow
      up of 35 months. SETTING: Tertiary cancer care center. PATIENTS: Fifty-one
      patients with clinically node-negative cutaneous melanoma of the head and neck
      region staged by means of SLNB. INTERVENTIONS: Sentinel lymph nodes (SLNs) were
      identified using preoperative lymphatic mapping along with intraoperative gamma
      probe evaluation and isosulfan blue dye injection. Patients with a positive SLNB
      finding by hematoxylin-eosin or immunohistochemical evaluation underwent
      completion lymphadenectomy of the affected lymphatic basin and were considered
      for further adjuvant treatment. Patients with a negative SLNB finding were
      observed clinically. MAIN OUTCOME MEASURES: Location characteristics of SLNs,
      incidence of positive SLNs, same-basin recurrence, and disease-free survival.
      RESULTS: The mean number of SLNs per patients was 2.75. The extent of SLNB
      included removal of 1 node (n = 11), multiple nodes from 1 basin (n = 18), 1 node
      in multiple basins (n = 7), and multiple nodes in multiple basins (n = 15).
      Drainage to unexpected basins was found in 13 of 51 patients. Parotid region
      drainage was identified in 18 patients. There were no same-basin recurrences in
      patients with a negative SLNB finding. Thirty-six-month disease-free survival was
      88.9% for patients with a negative SLN and 72.9% for patients with a positive SLN
      (P=.17). CONCLUSIONS: The number and location of SLNs is variable and difficult
      to predict for head and neck cutaneous melanoma. Preoperative lymphoscintigraphy
      is an important planning instrument to guide complete removal of all SLNs. Based
      on 3-year follow-up, this procedure can be expected to provide low same-basin
      recurrence rates for patients with a negative SLN.

PMID- 15262762
TI  - Mucoepidermoid carcinoma of the parotid gland: the Mayo clinic experience.
AB  - OBJECTIVE: To determine clinical and histopathologic features of mucoepidermoid
      carcinoma of the parotid gland, specifically, the relation of tumor stage and
      grade and treatment type with clinical outcome. DESIGN: Retrospective clinical
      and histopathologic review. SETTING: Tertiary care medical center. PATIENTS: From
      1940 to 1994, 128 patients were treated at our institution for parotid
      mucoepidermoid carcinoma. Eighty-nine of these patients had their first treatment
      at our institution; these cases were chosen for retrospective clinical and
      histopathologic review. INTERVENTION: A head and neck pathologist independently
      reviewed the pathology specimens. MAIN OUTCOME MEASURES: Age, symptoms, stage,
      treatment type, tumor grade, pathological features, disease progression, and
      survival. RESULTS: Results of clinical staging were: T1 in 56 patients, T2 in 13,
      T3 in 1, T4 in 15, N0 in 85, N1 in 2, and N2 in 2. No patient had N3 or M1
      disease. All patients underwent parotidectomy with or without neck dissection.
      Seven patients received postoperative radiotherapy. Tumor grade was low in 43
      patients (48%), intermediate in 40 (45%), and high in 6 (7%). Only 5 patients had
      disease progression (local recurrence in 4, regional recurrence in 4, and distant
      recurrence in 2). At latest follow-up (mean follow-up, 14.7 years), 64 patients
      were alive without disease, 1 was alive with disease, 2 had died of
      mucoepidermoid carcinoma, and 22 had died of other causes. The Kaplan-Meier
      estimated cancer-specific survival rates at 5, 15, and 25 years were 98.8%,
      97.4%, and 97.4%, respectively. CONCLUSIONS: In our study, tumor grade and stage
      appeared to be less important than previously described. With adequate
      parotidectomy and appropriate neck dissection, patients with mucoepidermoid
      carcinoma of the parotid gland appear to do well, with few recurrences.

PMID- 15262763
TI  - Patterns of lateral neck metastasis in papillary thyroid carcinoma.
AB  - BACKGROUND: Although lymphatic metastasis does not affect overall survival for
      patients with differentiated thyroid carcinoma, locoregional control can be
      improved with cervical lymphadenectomy. The major morbidity of neck dissection
      (ND) for the management of regional metastases is spinal accessory (cranial nerve
      XI) dysfunction. To avoid this complication, some surgeons have advocated a
      limited ND. OBJECTIVE: To establish the patterns of lateral cervical metastases
      in differentiated thyroid carcinoma and the role of comprehensive ND, we
      performed a review of our experience with comprehensive ND. STUDY DESIGN:
      Retrospective chart review. PATIENTS AND METHODS: Between 1997 and 2002, a total
      of 39 consecutive patients (31 women and 8 men) underwent 44 NDs for the
      management of lateral cervical metastases. Preoperative cytologic analysis
      revealed papillary carcinoma in all 39 patients (100%). All specimens were
      labeled and mapped by the operating surgeon to identify each level. The incidence
      of positive disease was determined in relation to the extent of lymphadenectomy
      for all dissected levels. RESULTS: All patients underwent ND at levels II through
      V; 7 (17%) of the 44 ND specimens included level I nodes. The incidence of
      metastatic disease in level II nodes was 52% (23/44 specimens). Similarly, 25
      specimens (57%) contained histologic metastases at level III. Metastatic disease
      was noted in 18 level IV nodes (41%) and 9 level V nodes (21%). One (14%) of the
      7 specimens with level I nodes contained tumor. CONCLUSIONS: Cervical metastases
      from papillary thyroid carcinoma occur in predictable patterns, with disease
      commonly present at levels II through V. We believe that a comprehensive ND,
      including removal of transverse cervical and spinal accessory nodes, is necessary
      for the complete clearance of lateral metastases.

PMID- 15262764
TI  - Intensive chemoradiotherapy as a primary treatment for organ preservation in
      patients with advanced cancer of the head and neck: efficacy, toxic effects, and
      limitations.
AB  - OBJECTIVES: To evaluate the efficacy and toxic effects of intensive
      chemoradiotherapy as a primary modality for organ preservation in patients with
      advanced squamous cell carcinoma of the head and neck (SCCHN) and to define the
      patterns of treatment failure associated with this therapy. DESIGN: Retrospective
      review. SETTING: Tertiary care referral center. PATIENTS: A total of 127
      consecutive patients with advanced SCCHN treated with primary concurrent
      chemoradiotherapy. MAIN OUTCOME MEASURES: Efficacy data included the rates of
      tumor response to therapy, organ preservation, disease recurrence, overall and
      disease-specific survival, and patterns of treatment failure. Toxic effect data
      included the rate and grade of treatment-related complications and the rate of
      unscheduled hospital admissions for managing treatment-related toxic effects.
      RESULTS: Ninety-six patients (76%) were men and 31 (24%) were women. Average age
      at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the
      oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20
      (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients
      (91%) had stage III or IV disease. Average follow-up was 36 months. Primary
      chemoradiotherapy achieved complete response at the primary tumor site in 109
      patients (86%). Patients with partial response, stable or progressive disease, or
      recurrence at the primary site underwent salvage surgery. Overall, at mean follow
      up of 3 years, local disease control was achieved in 113 patients (89%), and
      organ preservation was possible in 102 patients (80%). Two thirds of all patients
      (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy
      in the neck was achieved in 57 of these patients (69%). However, complete
      response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease,
      respectively (P <.001). Patients achieving less than complete clinical response
      underwent salvage neck dissection. Overall, at an average follow-up of 36 months,
      regional disease control was achieved in 76 (92%) of the 83 patients with neck
      metastasis. Despite this high locoregional control rate, distant metastasis
      occurred in 18 patients (14%), was the most common site of disease recurrence
      (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or
      4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively.
      Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow
      up, disease-specific and overall survival were 72% and 57%, respectively. Most
      deaths were due to distant metastasis, comorbidity, and second primary tumors.
      CONCLUSIONS: High rates of locoregional disease control and organ preservation
      are achievable with primary chemoradiotherapy in patients with advanced SCCHN,
      but they are associated with severe treatment-related toxic effects. Despite this
      effective local and regional disease control, improved survival is hampered by
      the relatively high incidence of distant metastasis, second primary tumors, and
      comorbidity.

PMID- 15262765
TI  - Matched analysis of survival in patients with squamous cell carcinoma of the head
      and neck diagnosed before and after 40 years of age.
AB  - OBJECTIVES: To compare the survival rates of patients 40 years or younger and
      diagnosed with squamous cell carcinoma of the head and neck (SCCHN) with those of
      patients older than 40 years who underwent the same treatment. In 2 previous
      matched-pair analyses, the patients had been matched for tumor stage, site, sex,
      and date of presentation but not type of treatment. METHODS: Between 1995 and
      2001, 46 patients 40 years or younger participated in a prospective epidemiologic
      study that included more than 500 patients newly diagnosed with SCCHN. We matched
      each of these patients by sex, race, tumor site, overall stage, and treatment
      modality with 2 patients older than 40 years. Ultimately, 31 of the younger
      patients were matched with 62 of the older patients. Survival analysis was
      performed using Cox proportional hazard models and accounting for the matched
      trios. RESULTS: There was no difference in overall, disease-specific, or
      recurrence-free survival rates between the patients who were 40 years or younger
      and those older than 40 years. Furthermore, matched survival analysis did not
      demonstrate a difference in overall survival rate (risk ratio [RR], 0.71; 95%
      confidence interval [CI], 0.22-2.29; P =.56), disease-free survival rate (RR,
      0.83; 95% CI, 0.20-3.33; P =.79), or time to recurrence (RR, 1.46; 95% CI, 0.50
      4.23; P =.49), and was not affected by adjustment for medical comorbidities or
      the severity of cancer-associated symptoms. CONCLUSIONS: We found no evidence of
      a difference in the survival rates of patients with SCCHN who were 40 years or
      younger or older than 40 years and underwent similar treatment at our
      institution.

PMID- 15262766
TI  - Quality of life for patients following total laryngectomy vs chemoradiation for
      laryngeal preservation.
AB  - BACKGROUND: The incorporation of chemotherapy and radiation, either sequentially
      or concurrently, has been increasingly used for organ preservation in patients
      with advanced laryngeal cancer. Traditional outcome measures of clinical response
      such as locoregional control and survival have been similar for patients treated
      with chemoradiotherapy and those treated with total laryngectomy (TL). The impact
      of concurrent chemoradiotherapy for laryngeal preservation on the overall quality
      of life (QOL) of patients has not been clearly evaluated, particularly in direct
      comparison with TL. OBJECTIVE: To compare the QOL of patients treated with
      concurrent chemoradiotherapy with those treated with TL. DESIGN: Nonrandomized,
      retrospective, cross-sectional study. SETTING: Academic tertiary care referral
      center. METHODS: The study included 42 patients with advanced stage III or IV
      cancer of the larynx, who were treated with either concurrent chemoradiotherapy
      or TL with postoperative radiation therapy. Patients had to be without evidence
      of recurrence and to have completed therapy at least 3 months prior to inclusion
      in the study. Quality of life was measured using the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ
      C30) in tandem with the head and neck module (EORTC QLQ-H&N35). RESULTS: On the
      core questionnaire (QLQ-C30), there were no statistically significant differences
      in the overall QOL score between the 2 groups. Functional subscale analysis
      revealed a trend for patients in the surgery and radiotherapy group to experience
      greater difficulties with social functioning (P =.18) relative to the
      chemoradiation group. On the QLQ-H&N35, surgery patients reported significantly
      greater difficulties with sensory disturbances (smell and taste, P =.001), use of
      painkillers (P =.049), and coughing (P =.004). On the other hand, chemoradiation
      patients reported significantly greater problems with dry mouth (P =.02).
      CONCLUSIONS: Both chemoradiation and TL affect, albeit differently, the QOL of
      patients treated for advanced cancer of the larynx. Although these differences
      can be detected by functional and subscale analysis, the overall QOL scores of
      both groups seem similar.

PMID- 15262768
TI  - Pathology quiz case 1. Cutaneous nasal sarcoidosis.

PMID- 15262767
TI  - Giant juvenile nasopharyngeal angiofibroma: management by skull-base surgery.
AB  - From 1977 to 2001, 5 patients were seen with giant angiofibromas that had
      intracranial penetration. Three of these had involvement of the cavernous sinus
      with angiographic evidence of significant blood supply to the tumor. We attempted
      complete tumor removal in all patients via a skull-base procedure. The
      infratemporal fossa/middle fossa approach was used in 3 patients, an anterior
      craniofacial approach in 1, and an anterior subcranial approach in 1. Complete
      tumor removal was achieved in 4 patients and incomplete excision in 1. The latter
      was attempted with an anterior subcranial approach but required an infratemporal
      fossa/middle fossa approach for completion because of unanticipated cavernous
      sinus involvement. The patient declined further surgery. This was the only
      patient who had persistent disease. Preoperative and intraoperative management,
      blood loss, complications, and residual effects are described.

PMID- 15262769
TI  - Pathology quiz case 2. Angiomyoma of the larynx.

PMID- 15262770
TI  - Radiology quiz case 1. Metastatic renal cell carcinoma, clear cell type.

PMID- 15262771
TI  - Radiology quiz case 2. Laryngeal low-grade chondrosarcoma.

PMID- 15262772
TI  - Factors predisposing to perinatal death related to uterine rupture during
      attempted vaginal birth after caesarean section: retrospective cohort study.
AB  - OBJECTIVE: To determine the factors associated with an increased risk of
      perinatal death related to uterine rupture during attempted vaginal birth after
      caesarean section. DESIGN: Population based retrospective cohort study. SETTING:
      Data from the linked Scottish Morbidity Record and Stillbirth and Infant Death
      Survey of births in Scotland, 1985-98. PARTICIPANTS: All women with one previous
      caesarean delivery who gave birth to a singleton infant at term by a means other
      than planned repeat caesarean section (n = 35 854). MAIN OUTCOME MEASURES: All
      intrapartum uterine rupture and uterine rupture resulting in perinatal death
      (that is, death of the fetus or neonate). RESULTS: The overall proportion of
      vaginal births was 74.2% and of uterine rupture was 0.35%. The risk of
      intrapartum uterine rupture was higher among women who had not previously given
      birth vaginally (adjusted odds ratio 2.5, 95% confidence interval 1.6 to 3.9, P <
      0.001) and those whose labour was induced with prostaglandin (2.9, 2.0 to 4.3, P
      < 0.001). Both factors were also associated with an increased risk of perinatal
      death due to uterine rupture. Delivery in a hospital with < 3000 births a year
      did not increase the overall risk of uterine rupture (1.1, 0.8 to 1.5, P = 0.67).
      However, the risk of perinatal death due to uterine rupture was significantly
      higher in hospitals with < 3000 births a year (one per 1300 births) than in
      hospitals with >or= 3000 births a year (one per 4700; 3.4, 1.0 to 14.3, P =
      0.04). CONCLUSION: Women who have not previously given birth vaginally and those
      whose labour is induced with prostaglandin are at increased risk of uterine
      rupture when attempting vaginal birth after caesarean section. The risk of
      consequent death of the infant is higher in units with lower annual numbers of
      births.

PMID- 15262775
TI  - Application of a new probabilistic model for recognizing complex patterns in
      glycans.
AB  - MOTIVATION: The study of carbohydrate sugar chains, or glycans, has been one of
      slow progress mainly due to the difficulty in establishing standard methods for
      analyzing their structures and biosynthesis. Glycans are generally tree
      structures that are more complex than linear DNA or protein sequences, and
      evidence shows that patterns in glycans may be present that spread across
      siblings and into further regions that are not limited by the edges in the actual
      tree structure itself. Current models were not able to capture such patterns.
      RESULTS: We have applied a new probabilistic model, called probabilistic sibling
      dependent tree Markov model (PSTMM), which is able to inherently capture such
      complex patterns of glycans. Not only is the ability to capture such patterns
      important in itself, but this also implies that PSTMM is capable of performing
      multiple tree structure alignments efficiently. We prove through experimentation
      on actual glycan data that this new model is extremely useful for gaining insight
      into the hidden, complex patterns of glycans, which are so crucial for the
      development and functioning of higher level organisms. Furthermore, we also show
      that this model can be additionally utilized as an innovative approach to
      multiple tree alignment, which has not been applied to glycan chains before. This
      extension on the usage of PSTMM may be a major step forward for not only the
      structural analysis of glycans, but it may consequently prove useful for
      discovering clues into their function.

PMID- 15262776
TI  - A knowledge based approach for representing and reasoning about signaling
      networks.
AB  - MOTIVATION: In this paper we propose to use recent developments in knowledge
      representation languages and reasoning methodologies for representing and
      reasoning about signaling networks. Our approach is different from most other
      qualitative systems biology approaches in that it is based on reasoning (or
      inferencing) rather than simulation. Some of the advantages of our approach are,
      we can use recent advances in reasoning with incomplete and partial information
      to deal with gaps in signal network knowledge; and can perform various kinds of
      reasoning such as planning, hypothetical reasoning and explaining observations.
      RESULTS: Using our approach we have developed the system BioSigNet-RR for
      representation and reasoning about signaling networks. We use a NFkappaB related
      signaling pathway to illustrate the kinds of reasoning and representation that
      our system can currently do. AVAILABILITY: The system is available on the Web at
      http://www.public.asu.edu/~cbaral/biosignet

PMID- 15262777
TI  - Deconvolving cell cycle expression data with complementary information.
AB  - MOTIVATION: In the study of many systems, cells are first synchronized so that a
      large population of cells exhibit similar behavior. While synchronization can
      usually be achieved for a short duration, after a while cells begin to lose their
      synchronization. Synchronization loss is a continuous process and so the observed
      value in a population of cells for a gene at time t is actually a convolution of
      its values in an interval around t. Deconvolving the observed values from a mixed
      population will allow us to obtain better models for these systems and to
      accurately detect the genes that participate in these systems. RESULTS: We
      present an algorithm which combines budding index and gene expression data to
      deconvolve expression profiles. Using the budding index data we first fit a
      synchronization loss model for the cell cycle system. Our deconvolution algorithm
      uses this loss model and can also use information from co-expressed genes, making
      it more robust against noise and missing values. Using expression and budding
      data for yeast we show that our algorithm is able to reconstruct a more accurate
      representation when compared with the observed values. In addition, using the
      deconvolved profiles we are able to correctly identify 15% more cycling genes
      when compared to a set identified using the observed values. AVAILABILITY: Matlab
      implementation can be downloaded from the supporting website
      http://www.cs.cmu.edu/~zivbj/decon/decon.html

PMID- 15262778
TI  - Statistical modeling of sequencing errors in SAGE libraries.
AB  - MOTIVATION: Sequencing errors may bias the gene expression measurements made by
      Serial Analysis of Gene Expression (SAGE). They may introduce non-existent tags
      at low abundance and decrease the real abundance of other tags. These effects are
      increased in the longer tags generated in LongSAGE libraries. Current sequencing
      technology generates quite accurate estimates of sequencing error rates. Here we
      make use of the sequence neighborhood of SAGE tags and error estimates from the
      base-calling software to correct for such errors. RESULTS: We introduce a
      statistical model for the propagation of sequencing errors in SAGE and suggest an
      Expectation-Maximization (EM) algorithm to correct for them given observed
      sequences in a library and base-calling error estimates. We tested our method
      using simulated and experimental SAGE libraries. When comparing SAGE libraries,
      we found that sequencing errors can introduce considerable bias. High abundance
      tags may be falsely called as significantly differentially expressed, especially
      when comparing libraries with different levels of sequencing errors and/or of
      different size. Truly, differentially expressed tags have decreased significance
      as 'true'-tag counts are generally underestimated. This may alter if tags near
      the threshold of differential expression are called significant. Moreover, the
      number of different transcripts present in a library is overestimated as false
      tags are introduced at low abundance. Our correction method adjusts the tag
      counts to be closer to the true counts and is able to partly correct for biases
      introduced by sequencing errors. AVAILABILITY: An implementation using R is
      distributed as an R package. An online version is available at
      http://tagcalling.mbgproject.org

PMID- 15262779
TI  - Into the heart of darkness: large-scale clustering of human non-coding DNA.
AB  - MOTIVATION: It is currently believed that the human genome contains about twice
      as much non-coding functional regions as it does protein-coding genes, yet our
      understanding of these regions is very limited. RESULTS: We examine the
      intersection between syntenically conserved sequences in the human, mouse and rat
      genomes, and sequence similarities within the human genome itself, in search of
      families of non-protein-coding elements. For this purpose we develop a graph
      theoretic clustering algorithm, akin to the highly successful methods used in
      elucidating protein sequence family relationships. The algorithm is applied to a
      highly filtered set of about 700 000 human-rodent evolutionarily conserved
      regions, not resembling any known coding sequence, which encompasses 3.7% of the
      human genome. From these, we obtain roughly 12 000 non-singleton clusters, dense
      in significant sequence similarities. Further analysis of genomic location,
      evidence of transcription and RNA secondary structure reveals many clusters to be
      significantly homogeneous in one or more characteristics. This subset of the
      highly conserved non-protein-coding elements in the human genome thus contains
      rich family-like structures, which merit in-depth analysis. AVAILABILITY:
      Supplementary material to this work is available at
      http://www.soe.ucsc.edu/~jill/dark.html

PMID- 15262780
TI  - Automatic quality assessment of peptide tandem mass spectra.
AB  - MOTIVATION: A powerful proteomics methodology couples high-performance liquid
      chromatography (HPLC) with tandem mass spectrometry and database-search software,
      such as SEQUEST. Such a set-up, however, produces a large number of spectra, many
      of which are of too poor quality to be useful. Hence a filter that eliminates
      poor spectra before the database search can significantly improve throughput and
      robustness. Moreover, spectra judged to be of high quality, but that cannot be
      identified by database search, are prime candidates for still more
      computationally intensive methods, such as de novo sequencing or wider database
      searches including post-translational modifications. RESULTS: We report on two
      different approaches to assessing spectral quality prior to identification:
      binary classification, which predicts whether or not SEQUEST will be able to make
      an identification, and statistical regression, which predicts a more universal
      quality metric involving the number of b- and y-ion peaks. The best of our binary
      classifiers can eliminate over 75% of the unidentifiable spectra while losing
      only 10% of the identifiable spectra. Statistical regression can pick out spectra
      of modified peptides that can be identified by a de novo program but not by
      SEQUEST. In a section of independent interest, we discuss intensity normalization
      of mass spectra.

PMID- 15262781
TI  - Analysis of domain correlations in yeast protein complexes.
AB  - MOTIVATION: A growing body of research has concentrated on the identification and
      definition of conserved sequence motifs. It is widely recognized that these
      conserved sequence and structural units often mediate protein functions and
      interactions. The continuing advancements in high-throughput experiments
      necessitate the development of computational methods to critically assess the
      results. In this work, we analyzed high-throughput protein complexes using the
      domain composition of their protein constituents. Domains that mediate similar or
      related functions may consistently co-occur in protein complexes. RESULTS: We
      analyzed Saccharomyces cerevisiae protein complexes from curated and high
      throughput experimental datasets to identify statistically significant functional
      associations between domains. The resulting correlations are represented as
      domain networks that form the basis of comparison between the datasets, as well
      as to binary protein interactions. The results show that the curated datasets
      produce domain networks that map to known biological assemblies, such as
      ribosome, RNA polymerase, proteasome regulators, transcription initiation and
      histones. Furthermore, many of these domain correlations were also found in
      binary protein interactions. In contrast, the high-throughput datasets contain
      one large network of domain associations. High connectivity of RNA processing and
      binding domains in the high-throughput datasets reflects the abundance of RNA
      binding proteins in yeast, in agreement with a previous report that identified a
      nucleolar protein cluster, possibly mediated by rRNA, from these complexes.
      AVAILABILITY: The software is available upon request from the authors and is
      dependent on the NCBI C++ toolkit.

PMID- 15262782
TI  - A neural-network-based method for predicting protein stability changes upon
      single point mutations.
AB  - MOTIVATION: One important requirement for protein design is to be able to predict
      changes of protein stability upon mutation. Different methods addressing this
      task have been described and their performance tested considering global linear
      correlation between predicted and experimental data. Neither is direct
      statistical evaluation of their prediction performance available, nor is a direct
      comparison among different approaches possible. Recently, a significant database
      of thermodynamic data on protein stability changes upon single point mutation has
      been generated (ProTherm). This allows the application of machine learning
      techniques to predicting free energy stability changes upon mutation starting
      from the protein sequence. RESULTS: In this paper, we present a neural-network
      based method to predict if a given mutation increases or decreases the protein
      thermodynamic stability with respect to the native structure. Using a dataset
      consisting of 1615 mutations, our predictor correctly classifies >80% of the
      mutations in the database. On the same task and using the same data, our
      predictor performs better than other methods available on the Web. Moreover, when
      our system is coupled with energy-based methods, the joint prediction accuracy
      increases up to 90%, suggesting that it can be used to increase also the
      performance of pre-existing methods, and generally to improve protein design
      strategies. AVAILABILITY: The server is under construction and will be available
      at http://www.biocomp.unibo.it

PMID- 15262783
TI  - Splice site identification by idlBNs.
AB  - MOTIVATION: Computational identification of functional sites in nucleotide
      sequences is at the core of many algorithms for the analysis of genomic data.
      This identification is based on the statistical parameters estimated from a
      training set. Often, because of the huge number of parameters, it is difficult to
      obtain consistent estimators. To simplify the estimation problem, one imposes
      independent assumptions between the nucleotides along the site. However, this can
      potentially limit the minimum value of the estimation error. RESULTS: In this
      paper, we introduce a novel method in the context of identifying functional
      sites, that finds a reasonable set of independence assumptions supported by the
      data, among the nucleotides, and uses it to perform the identification of the
      sites by their likelihood ratio. More importantly, in many practical situations
      it is capable of improving its performance as the training sample size increases.
      We apply the method to the identification of splice sites, and further evaluate
      its effect within the context of exon and gene prediction.

PMID- 15262784
TI  - Mining frequent patterns in protein structures: a study of protease families.
AB  - MOTIVATION: Analysis of protein sequence and structure databases usually reveal
      frequent patterns (FP) associated with biological function. Data mining
      techniques generally consider the physicochemical and structural properties of
      amino acids and their microenvironment in the folded structures. Dynamics is not
      usually considered, although proteins are not static, and their function relates
      to conformational mobility in many cases. RESULTS: This work describes a novel
      unsupervised learning approach to discover FPs in the protein families, based on
      biochemical, geometric and dynamic features. Without any prior knowledge of
      functional motifs, the method discovers the FPs for each type of amino acid and
      identifies the conserved residues in three protease subfamilies; chymotrypsin and
      subtilisin subfamilies of serine proteases and papain subfamily of cysteine
      proteases. The catalytic triad residues are distinguished by their strong spatial
      coupling (high interconnectivity) to other conserved residues. Although the
      spatial arrangements of the catalytic residues in the two subfamilies of serine
      proteases are similar, their FPs are found to be quite different. The present
      approach appears to be a promising tool for detecting functional patterns in
      rapidly growing structure databases and providing insights in to the relationship
      among protein structure, dynamics and function. AVAILABILITY: Available upon
      request from the authors.

PMID- 15262785
TI  - Selecting biomedical data sources according to user preferences.
AB  - MOTIVATION: Biologists are now faced with the problem of integrating information
      from multiple heterogeneous public sources with their own experimental data
      contained in individual sources. The selection of the sources to be considered is
      thus critically important. RESULTS: Our aim is to support biologists by
      developing a module based on an algorithm that presents a selection of sources
      relevant to their query and matched to their own preferences. We approached this
      task by investigating the characteristics of biomedical data and introducing
      several preference criteria useful for bioinformaticians. This work was carried
      out in the framework of a project which aims to develop an integrative platform
      for the multiple parametric analysis of cancer. We illustrate our study through
      an elementary biomedical query occurring in a CGH analysis scenario.
      AVAILABILITY: http://www.lri.fr/~cohen/dss/dss.html

PMID- 15262786
TI  - Improved techniques for the identification of pseudogenes.
AB  - MOTIVATION: Pseudogenes are the remnants of genomic sequences of genes which are
      no longer functional. They are frequent in most eukaryotic genomes, and an
      important resource for comparative genomics. However, pseudogenes are often mis
      annotated as functional genes in sequence databases. Current methods for
      identifying pseudogenes include methods which rely on the presence of stop codons
      and frameshifts, as well as methods based on the ratio of non-silent to silent
      nucleotide substitution rates (dN/dS). A recent survey concluded that 50% of
      human pseudogenes have no detectable truncation in their pseudo-coding regions,
      indicating that the former methods lack sensitivity. The latter methods have been
      used to find sets of genes enriched for pseudogenes, but are not specific enough
      to accurately separate pseudogenes from expressed genes. RESULTS: We introduce a
      program called pseudogene inference from loss of constraint (PSILC) which
      incorporates novel methods for separating pseudogenes from functional genes. The
      methods calculate the log-odds score that evolution along the final branch of the
      gene tree to the query gene has been according to the following constraints: A
      neutral nucleotide model compared to a Pfam domain encoding model
      (PSILC(nuc/dom)); A protein coding model compared to a Pfam domain encoding model
      (PSILC(prot/dom)). Using the manual annotation of human chromosome 6, we show
      that both these methods result in a more accurate classification of pseudogenes
      than dN/dS when a Pfam domain alignment is available. AVAILABILITY: PSILC is
      available from http://www.sanger.ac.uk/Software/PSILC

PMID- 15262787
TI  - Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide
      data.
AB  - MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis
      at the transcriptional level. We assess the accuracy of a fold-change analysis,
      Bayesian networks, dynamic models and supervised learning based on coregulation
      in predicting gene regulation by sigma factors from gene expression data. To
      improve the prediction accuracy, we combine sequence information with expression
      data by adding their log-likelihood scores and by using a logistic regression
      model. We use the resulting score function to discover currently unknown gene
      regulations by sigma factors. RESULTS: The coregulation-based supervised learning
      method gave the most accurate prediction of sigma factors from expression data.
      We found that the logistic regression model effectively combines expression data
      with sequence information. In a genome-wide search, highly significant logistic
      regression scores were found for several genes whose transcriptional regulation
      is currently unknown. We provide the corresponding RNA polymerase binding sites
      to enable a straightforward experimental verification of these predictions.

PMID- 15262788
TI  - Functional inference from non-random distributions of conserved predicted
      transcription factor binding sites.
AB  - MOTIVATION: Our understanding of how genes are regulated in a concerted fashion
      is still limited. Especially, complex phenomena like cell cycle regulation in
      multicellular organisms are poorly understood. Therefore, we investigated
      conserved predicted transcription factor binding sites (TFBSs) in man-mouse
      upstream regions of genes that can be associated to a particular cell cycle phase
      in HeLa cells. TFBSs were predicted from selected binding site motifs
      (represented by position weight matrices, PWMs) based on a statistical approach.
      A regulatory role for a transcription factor is more probable if its predicted
      TFBSs are enriched in upstream regions of genes, that are associated with a
      subset of cell cycle phases. We tested for this association by computing exact P
      values for the observed phase distributions under the null distribution defined
      by the relative amount of conserved upstream sequence of genes per cell cycle
      phase. We considered non-exonic and 5'-untranslated region (5'-UTR) binding sites
      separately and corrected for multiple testing by taking the false discovery rate
      into account. RESULTS: We identified 22 non-exonic and 11 5'-UTR significant PWM
      phase distributions although expecting one false discovery. Many of the
      corresponding transcription factors (e.g. members of the thyroid hormone/retinoid
      receptor subfamily) have already been associated with cell cycle regulation,
      proliferation and development. It appears that our method is a suitable tool for
      detecting putative cell cycle regulators in the realm of known human
      transcription factors. AVAILABILITY: Further details and supplementary data can
      be obtained from http://corg.molgen.mpg.de/cellcycle

PMID- 15262789
TI  - Phylogenomics and the number of characters required for obtaining an accurate
      phylogeny of eukaryote model species.
AB  - MOTIVATION: Through the most extensive phylogenomic analysis carried out to date,
      complete genomes of 11 eukaryotic species have been examined in order to find the
      homologous of more than 25,000 amino acid sequences. These sequences correspond
      to the exons of more than 3000 genes and were used as presence/absence characters
      to test one of the most controversial hypotheses concerning animal evolution,
      namely the Ecdysozoa hypothesis. Distance, maximum parsimony and Bayesian methods
      of phylogenetic reconstruction were used to test the hypothesis. RESULTS: The
      reliability of the ecdysozoa, grouping arthropods and nematodes in a single clade
      was unequivocally rejected in all the consensus trees. The Coelomata clade,
      grouping arthropods and chordates, was supported by the highest statistical
      confidence in all the reconstructions. The study of the dependence of the
      genomes' tree accuracy on the number of exons used, demonstrated that an
      unexpectedly larger number of characters are necessary to obtain robust
      phylogenies. Previous studies supporting ecdysozoa, could not guarantee an
      accurate phylogeny because the number of characters used was clearly below the
      minimum required.

PMID- 15262790
TI  - Assigning transmembrane segments to helices in intermediate-resolution
      structures.
AB  - MOTIVATION: Transmembrane (TM) proteins that form alpha-helix bundles constitute
      approximately 50% of contemporary drug targets. Yet, it is difficult to determine
      their high-resolution (< 4 A) structures. Some TM proteins yield more easily to
      structure determination using cryo electron microscopy (cryo-EM), though this
      technique most often results in lower resolution structures, precluding an
      unambiguous assignment of TM amino acid sequences to the helices seen in the
      structure. We present computational tools for assigning the TM segments in the
      protein's sequence to the helices seen in cryo-EM structures. RESULTS: The method
      examines all feasible TM helix assignments and ranks each one based on a score
      function that was derived from loops in the structures of soluble alpha-helix
      bundles. A set of the most likely assignments is then suggested. We tested the
      method on eight TM chains of known structures, such as bacteriorhodopsin and the
      lactose permease. Our results indicate that many assignments can be rejected at
      the outset, since they involve the connection of pairs of remotely placed TM
      helices. The correct assignment received a high score, and was ranked highly
      among the remaining assignments. For example, in the lactose permease, which
      contains 12 TM helices, most of which are connected by short loops, only 12 out
      of 479 million assignments were found to be feasible, and the native one was
      ranked first. AVAILABILITY: The program and the non-redundant set of protein
      structures used here are available at http://www.cs.tau.ac.il/~angela

PMID- 15262791
TI  - SCOPEC: a database of protein catalytic domains.
AB  - MOTIVATION: Domains are the units of protein structure, function and evolution.
      It is therefore essential to utilize knowledge of domains when studying the
      evolution of function, or when assigning function to genome sequence data. For
      this purpose, we have developed a database of catalytic domains, SCOPEC, by
      combining structural domain information from SCOP, full-length sequence
      information from Swiss-Prot, and verified functional information from the Enzyme
      Classification (EC) database. Two major problems need to be overcome to create a
      database of domain-function relationships; (1) for sequences, EC numbers are
      typically assigned to whole sequences rather than the functional unit, and (2)
      The Protein Data Bank (PDB) structures elucidated from a larger multi-domain
      protein will often have EC annotation although the relevant catalytic domain may
      lie elsewhere. RESULTS: SCOPEC entries have high quality enzyme assignments;
      having passed both computational and manual checks. SCOPEC currently contains
      entries for 75% of all EC annotations in the PDB. Overall, EC number is fairly
      well conserved within a superfamily, even when the proteins are distantly
      related. Initial analysis is encouraging; suggesting that there is a 50:50 chance
      of conserved function in distant homologues first detected by a third iteration
      PSI-BLAST search. Therefore, we envisage that a knowledge-based approach to
      function assignment using the domain-EC relationships in SCOPEC will gain a
      marked improvement over this base line. AVAILABILITY: The SCOPEC database is a
      valuable resource in the analysis and prediction of protein structure and
      function. It can be obtained or queried at our website http://www.enzome.com

PMID- 15262792
TI  - High density linkage disequilibrium mapping using models of haplotype block
      variation.
AB  - MOTIVATION: The presence of millions of single nucleotide polymorphisms (SNPs) in
      the human genome has spurred interest in genetic mapping methods based on linkage
      disequilibrium. The recently discovered haplotype block structure of human
      variation promises to improve the effectiveness of these methods. A key
      difficulty for mapping techniques is the cost involved in separately identifying
      the haplotypes on each of an individual's chromosomes. RESULTS: We present a new
      approach for performing linkage disequilibrium mapping using high density
      haplotype or genotype data. Our method is based on a statistical model of
      haplotype block variation, which takes account of recombination hotspots,
      bottlenecks, genetic drift and mutation. We test our technique on two empirically
      determined high density datasets, attempting to recover the location of an SNP
      which was hidden and converted into phenotype information. We compare the results
      against a mapping method based on individual SNPs as well as a competing
      haplotype-based approach. We show that our strategy significantly outperforms
      these other approaches when used as a guide for resequencing and that it can also
      deal with both unphased genotype data and low penetrance diseases. AVAILABILITY:
      HaploBlock executables for Linux, Mac OS X and Sun OS, as well as user
      documentation, are available online at
      http://bioinfo.cs.technion.ac.il/haploblock/

PMID- 15262793
TI  - The cell graphs of cancer.
AB  - We report a novel, proof-of-concept, computational method that models a type of
      brain cancer (glioma) only by using the topological properties of its cells in
      the tissue image. From low-magnification (80x) tissue images of 384 x 384 pixels,
      we construct the graphs of the cells based on the locations of the cells within
      the images. We generate such cell graphs of 1000-3000 cells (nodes) with 2000
      10,000 links, each of which is calculated as a decaying exponential function of
      the Euclidean distance between every pair of cells in accordance with the Waxman
      model. At the cellular level, we compute the graph metrics of the cell graphs,
      including the degree, clustering coefficient, eccentricity and closeness for each
      cell. Working with a total of 285 tissue samples surgically removed from 12
      different patients, we demonstrate that the self-organizing clusters of cancerous
      cells exhibit distinctive graph metrics that distinguish them from the healthy
      cells and the unhealthy inflamed cells at the cellular level with an accuracy of
      at least 85%. At the tissue level, we accomplish correct tissue classifications
      of cancerous, healthy and non-neoplastic inflamed tissue samples with an accuracy
      of 100% by requiring correct classification for the majority of the cells within
      the tissue sample.

PMID- 15262794
TI  - TraitMap: an XML-based genetic-map database combining multigenic loci and
      biomolecular networks.
AB  - MOTIVATION: Most ordinary traits are well described by multiple measurable
      parameters. Thus, in the course of elucidating the genes responsible for a given
      trait, it is necessary to conduct and integrate the genetic mapping of each
      parameter. However, the integration of multiple mapping results from different
      publications is prevented by the fact that they are conventionally published and
      accumulated in printed forms or graphics which are difficult for computers to
      reuse for further analyses. RESULTS: We have defined an XML-based schema as a
      container of genetic mapping results, and created a database named TraitMap
      containing curator-checked data records based on published papers of mapping
      results in Homosapiens, Mus musculus, and Arabidopsis thaliana. TraitMap is the
      first database of mapping charts in genetics, and is integrated in a web-based
      retrieval framework: termed Genome <--> Phenome Superhighway (GPS) system, where
      it is possible to combine and visualize multiple mapping records in a two
      dimensional display. Since most traits are regulated by multiple genes, the
      system associates every combination of genetic loci to biomolecular networks, and
      thus helps us to estimate molecular-level candidate networks responsible for a
      given trait. It is demonstrated that a combined analysis of two diabetes-related
      traits (susceptibility to insulin resistance and non-HDL cholesterol level)
      suggests that molecular-level relationships such as the interaction among leptin
      receptor (Lepr), peroxisome proliferators-activated receptor-gamma (Pparg) and
      insulin receptor substrate 1 (Irs1), are candidate causal networks affecting the
      traits in a multigenic manner. AVAILABILITY: TraitMap database and GPS are
      accessible at http://omicspace.riken.jp/gps/

PMID- 15262795
TI  - Efficient approximations for learning phylogenetic HMM models from data.
AB  - MOTIVATION: We consider models useful for learning an evolutionary or
      phylogenetic tree from data consisting of DNA sequences corresponding to the
      leaves of the tree. In particular, we consider a general probabilistic model
      described in Siepel and Haussler that we call the phylogenetic-HMM model which
      generalizes the classical probabilistic models of Neyman and Felsenstein.
      Unfortunately, computing the likelihood of phylogenetic-HMM models is
      intractable. We consider several approximations for computing the likelihood of
      such models including an approximation introduced in Siepel and Haussler, loopy
      belief propagation and several variational methods. RESULTS: We demonstrate that,
      unlike the other approximations, variational methods are accurate and are
      guaranteed to lower bound the likelihood. In addition, we identify a particular
      variational approximation to be best-one in which the posterior distribution is
      variationally approximated using the classic Neyman-Felsenstein model. The
      application of our best approximation to data from the cystic fibrosis
      transmembrane conductance regulator gene region across nine eutherian mammals
      reveals a CpG effect.

PMID- 15262796
TI  - The gene ontology categorizer.
AB  - The Gene Ontology Categorizer, developed jointly by the Los Alamos National
      Laboratory and Procter & Gamble Corp., provides a capability for the
      categorization task in the Gene Ontology (GO): given a list of genes of interest,
      what are the best nodes of the GO to summarize or categorize that list? The
      motivating question is from a drug discovery process, where after some gene
      expression analysis experiment, we wish to understand the overall effect of some
      cell treatment or condition by identifying 'where' in the GO the differentially
      expressed genes fall: 'clustered' together in one place? in two places? uniformly
      spread throughout the GO? 'high', or 'low'? In order to address this need, we
      view bio-ontologies more as combinatorially structured databases than facilities
      for logical inference, and draw on the discrete mathematics of finite partially
      ordered sets (posets) to develop data representation and algorithms appropriate
      for the GO. In doing so, we have laid the foundations for a general set of
      methods to address not just the categorization task, but also other tasks (e.g.
      distances in ontologies and ontology merger and exchange) in both the GO and
      other bio-ontologies (such as the Enzyme Commission database or the MEdical
      Subject Headings) cast as hierarchically structured taxonomic knowledge systems.

PMID- 15262797
TI  - Filling gaps in a metabolic network using expression information.
AB  - MOTIVATION: The metabolic models of both newly sequenced and well-studied
      organisms contain reactions for which the enzymes have not been identified yet.
      We present a computational approach for identifying genes encoding such missing
      metabolic enzymes in a partially reconstructed metabolic network. RESULTS: The
      metabolic expression placement (MEP) method relies on the coexpression properties
      of the metabolic network and is complementary to the sequence homology and genome
      context methods that are currently being used to identify missing metabolic
      genes. The MEP algorithm predicts over 20% of all known Saccharomyces cerevisiae
      metabolic enzyme-encoding genes within the top 50 out of 5594 candidates for
      their enzymatic function, and 70% of metabolic genes whose expression level has
      been significantly perturbed across the conditions of the expression dataset
      used. AVAILABILITY: Freely available (in Supplementary information).

PMID- 15262798
TI  - Optimal robust non-unique probe selection using Integer Linear Programming.
AB  - MOTIVATION: Besides their prevalent use for analyzing gene expression,
      microarrays are an efficient tool for biological, medical and industrial
      applications due to their ability to assess the presence or absence of biological
      agents, the targets, in a sample. Given a collection of genetic sequences of
      targets one faces the challenge of finding short oligonucleotides, the probes,
      which allow detection of targets in a sample. Each hybridization experiment
      determines whether the probe binds to its corresponding sequence in the target.
      Depending on the problem, the experiments are conducted using either unique or
      non-unique probes and usually assume that only one target is present in the
      sample. The problem at hand is to compute a design, i.e. a minimal set of probes
      that allows to infer the targets in the sample from the result of the
      hybridization experiment. If we allow to test for more than one target in the
      sample, the design of the probe set becomes difficult in the case of non-unique
      probes. RESULTS: Building upon previous work on group testing for microarrays, we
      describe the first approach to select a minimal probe set for the case of non
      unique probes in the presence of a small number of multiple targets in the
      sample. The approach is based on an ILP formulation and a branch-and-cut
      algorithm. Our preliminary implementation greatly reduces the number of probes
      needed while preserving the decoding capabilities. AVAILABILITY:
      http://www.inf.fu-berlin.de/inst/ag-bio

PMID- 15262799
TI  - Finding disease specific alterations in the co-expression of genes.
AB  - MOTIVATION: Standard analysis routines for microarray data aim at differentially
      expressed genes. In this paper, we address the complementary problem of detecting
      sets of differentially co-expressed genes in two phenotypically distinct sets of
      expression profiles. RESULTS: We introduce a score for differential co-expression
      and suggest a computationally efficient algorithm for finding high scoring sets
      of genes. The use of our novel method is demonstrated in the context of
      simulations and on real expression data from a clinical study.

PMID- 15262800
TI  - An efficient algorithm for detecting frequent subgraphs in biological networks.
AB  - MOTIVATION: With rapidly increasing amount of network and interaction data in
      molecular biology, the problem of effectively analyzing this data is an important
      one. Graph theoretic formalisms, commonly used for these analysis tasks, often
      lead to computationally hard problems due to their relation with subgraph
      isomorphism. RESULTS: This paper presents an innovative new algorithm for
      detecting frequently occurring patterns and modules in biological networks. Using
      an innovative graph simplification technique, which is ideally suited to
      biological networks, our algorithm renders these problems computationally
      tractable. Indeed, we show experimentally that our algorithm can extract
      frequently occurring patterns in metabolic pathways extracted from the KEGG
      database within seconds. The proposed model and algorithm are applicable to a
      variety of biological networks either directly or with minor modifications.
      AVAILABILITY: Implementation of the proposed algorithms in the C programming
      language is available as open source at
      http://www.cs.purdue.edu/homes/koyuturk/pathway/

PMID- 15262801
TI  - Partial Cox regression analysis for high-dimensional microarray gene expression
      data.
AB  - MOTIVATION: An important application of microarray technology is to predict
      various clinical phenotypes based on the gene expression profile. Success has
      been demonstrated in molecular classification of cancer in which different types
      of cancer serve as categorical outcome variable. However, there has been less
      research in linking gene expression profile to censored survival outcome such as
      patients' overall survival time or time to cancer relapse. In this paper, we
      develop a partial Cox regression method for constructing mutually uncorrelated
      components based on microarray gene expression data for predicting the survival
      of future patients. RESULTS: The proposed partial Cox regression method involves
      constructing predictive components by repeated least square fitting of residuals
      and Cox regression fitting. The key difference from the standard principal
      components of Cox regression analysis is that in constructing the predictive
      components, our method utilizes the observed survival/censoring information. We
      also propose to apply the time-dependent receiver operating characteristic curve
      analysis to evaluate the results. We applied our methods to a publicly available
      dataset of diffuse large B-cell lymphoma. The outcomes indicated that combining
      the partial Cox regression method with principal components analysis results in
      parsimonious model with fewer components and better predictive performance. We
      conclude that the proposed partial Cox regression method can be very useful in
      building a parsimonious predictive model that can accurately predict the survival
      of future patients based on the gene expression profile and survival times of
      previous patients. AVAILABILITY: R codes are available upon request.

PMID- 15262802
TI  - A nucleotide substitution model with nearest-neighbour interactions.
AB  - MOTIVATION: It is well known that neighbouring nucleotides in DNA sequences do
      not mutate independently of each other. In this paper, we introduce a context
      dependent substitution model and derive an algorithm to calculate the likelihood
      of sequences evolving under this model. We use this algorithm to estimate
      neighbour-dependent substitution rates, as well as rates for dinucleotide
      substitutions, using a Bayesian sampling procedure. The model is irreversible,
      giving an arrow to time, and allowing the position of the root between a pair of
      sequences to be inferred without using out-groups. RESULTS: We applied the model
      upon aligned human-mouse non-coding data. Clear neighbour dependencies were
      observed, including 17-18-fold increased CpG to TpG/CpA rates compared with other
      substitutions. Root inference positioned the root halfway the mouse and human
      tips, suggesting an approximately clock-like behaviour of the irreversible part
      of the substitution process.

PMID- 15262803
TI  - Striped sheets and protein contact prediction.
AB  - MOTIVATION: Current approaches to contact map prediction in proteins have focused
      on amino acid conservation and patterns of mutation at sequentially distant
      positions. This sequence information is poorly understood and very little
      progress has been made in this area during recent years. RESULTS: In this study,
      an observation of 'striped' sequence patterns across beta-sheets prompted the
      development of a new type of contact map predictor. Computer program code was
      evolved with an evolutionary algorithm (genetic programming) to select residues
      and residue pairs likely to make contacts based solely on local sequence patterns
      extracted with the help of self-organizing maps. The mean prediction accuracy is
      27% on a validation set of 156 domains up to 400 residues in length, where
      contacts are separated by at least 8 residues and length/10 pairs are predicted.
      The retrospective accuracy on a set of 15 CASP5 targets is 27% and 14% for
      length/10 and length/2 predicted pairs, respectively (both using a minimum
      residue separation of 24). This compares favourably to the equivalent 21% and 13%
      obtained for the best automated contact prediction methods at CASP5. The results
      suggest that protein architectures impose regularities in local sequence
      environments. Other sources of information, such as correlated/compensatory
      mutations, may further improve accuracy. AVAILABILITY: A web-based prediction
      service is available at http://www.sbc.su.se/~maccallr/contactmaps

PMID- 15262804
TI  - Predicting genetic regulatory response using classification.
AB  - MOTIVATION: Studying gene regulatory mechanisms in simple model organisms through
      analysis of high-throughput genomic data has emerged as a central problem in
      computational biology. Most approaches in the literature have focused either on
      finding a few strong regulatory patterns or on learning descriptive models from
      training data. However, these approaches are not yet adequate for making accurate
      predictions about which genes will be up- or down-regulated in new or held-out
      experiments. By introducing a predictive methodology for this problem, we can use
      powerful tools from machine learning and assess the statistical significance of
      our predictions. RESULTS: We present a novel classification-based method for
      learning to predict gene regulatory response. Our approach is motivated by the
      hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can
      learn a decision rule for predicting whether a gene is up- or down-regulated in a
      particular experiment based on (1) the presence of binding site subsequences
      ('motifs') in the gene's regulatory region and (2) the expression levels of
      regulators such as transcription factors in the experiment ('parents'). Thus, our
      learning task integrates two qualitatively different data sources: genome-wide
      cDNA microarray data across multiple perturbation and mutant experiments along
      with motif profile data from regulatory sequences. We convert the regression task
      of predicting real-valued gene expression measurements to a classification task
      of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond
      the levels of biological and measurement noise in microarray measurements. The
      learning algorithm employed is boosting with a margin-based generalization of
      decision trees, alternating decision trees. This large-margin classifier is
      sufficiently flexible to allow complex logical functions, yet sufficiently simple
      to give insight into the combinatorial mechanisms of gene regulation. We observe
      encouraging prediction accuracy on experiments based on the Gasch S.cerevisiae
      dataset, and we show that we can accurately predict up- and down-regulation on
      held-out experiments. We also show how to extract significant regulators, motifs
      and motif-regulator pairs from the learned models for various stress responses.
      Our method thus provides predictive hypotheses, suggests biological experiments,
      and provides interpretable insight into the structure of genetic regulatory
      networks. AVAILABILITY: The MLJava package is available upon request to the
      authors. Supplementary: Additional results are available from
      http://www.cs.columbia.edu/compbio/geneclass

PMID- 15262805
TI  - Protein names precisely peeled off free text.
AB  - MOTIVATION: Automatically identifying protein names from the scientific
      literature is a pre-requisite for the increasing demand in data-mining this
      wealth of information. Existing approaches are based on dictionaries, rules and
      machine-learning. Here, we introduced a novel system that combines a pre
      processing dictionary- and rule-based filtering step with several separately
      trained support vector machines (SVMs) to identify protein names in the MEDLINE
      abstracts. RESULTS: Our new tagging-system NLProt is capable of extracting
      protein names with a precision (accuracy) of 75% at a recall (coverage) of 76%
      after training on a corpus, which was used before by other groups and contains
      200 annotated abstracts. For our estimate of sustained performance, we considered
      partially identified names as false positives. One important issue frequently
      ignored in the literature is the redundancy in evaluation sets. We suggested some
      guidelines for removing overly inadequate overlaps between training and testing
      sets. Applying these new guidelines, our program appeared to significantly out
      perform other methods tagging protein names. NLProt was so successful due to the
      SVM-building blocks that succeeded in utilizing the local context of protein
      names in the scientific literature. We challenge that our system may constitute
      the most general and precise method for tagging protein names. AVAILABILITY:
      http://cubic.bioc.columbia.edu/services/nlprot/

PMID- 15262806
TI  - Inferring quantitative models of regulatory networks from expression data.
AB  - MOTIVATION: Genetic networks regulate key processes in living cells. Various
      methods have been suggested to reconstruct network architecture from gene
      expression data. However, most approaches are based on qualitative models that
      provide only rough approximations of the underlying events, and lack the
      quantitative aspects that are critical for understanding the proper function of
      biomolecular systems. RESULTS: We present fine-grained dynamical models of gene
      transcription and develop methods for reconstructing them from gene expression
      data within the framework of a generative probabilistic model. Unlike previous
      works, we employ quantitative transcription rates, and simultaneously estimate
      both the kinetic parameters that govern these rates, and the activity levels of
      unobserved regulators that control them. We apply our approach to expression
      datasets from yeast and show that we can learn the unknown regulator activity
      profiles, as well as the binding affinity parameters. We also introduce a novel
      structure learning algorithm, and demonstrate its power to accurately reconstruct
      the regulatory network from those datasets.

PMID- 15262807
TI  - HyBrow: a prototype system for computer-aided hypothesis evaluation.
AB  - MOTIVATION: Experimental design, hypothesis-testing and model-building in the
      current data-rich environment require the biologists' to collect, evaluate and
      integrate large amounts of information of many disparate kinds. Developing a
      unified framework for the representation and conceptual integration of biological
      data and processes is a major challenge in bioinformatics because of the variety
      of available data and the different levels of detail at which biological
      processes can be considered. RESULTS: We have developed the HyBrow (Hypothesis
      Browser) system as a prototype bioinformatics tool for designing hypotheses and
      evaluating them for consistency with existing knowledge. HyBrow consists of a
      modeling framework with the ability to accommodate diverse biological information
      sources, an event-based ontology for representing biological processes at
      different levels of detail, a database to query information in the ontology and
      programs to perform hypothesis design and evaluation. We demonstrate the HyBrow
      prototype using the galactose gene network in Saccharomyces cerevisiae as our
      test system, and evaluate alternative hypotheses for consistency with stored
      information. AVAILABILITY: www.hybrow.org

PMID- 15262808
TI  - Reconstructing tumor amplisomes.
AB  - MOTIVATION: Duplication of genomic sequences is a common phenomenon in tumor
      cells. While many duplications associated with tumors have been identified (e.g.
      via techniques such as CGH), both the organization of the duplicated sequences
      and the process that leads to these duplications are less clear. One mechanism
      that has been observed to lead to duplication is the extraction of DNA from the
      chromosomes and aggregation of this DNA into small, independently replicating
      linear or circular DNA sequences (amplisomes). Parts of these amplisomes may
      later be reinserted back into the main chromosomes leading to duplication.
      Although amplisomes are known to play an important role in tumorigenesis, their
      architecture and even size remain largely unknown. RESULTS: We reconstruct the
      structure of tumor amplisomes by analyzing duplications in the tumor genome. Our
      approach relies on recently generated data from End Sequence Profiling (ESP)
      experiments, which allow us to examine the fine structure of duplications in a
      tumor on a genome-wide scale. Using ESP data, we formulate the Amplisome
      Reconstruction Problem, describe an algorithm for its solution, and derive a
      putative architecture of a tumor amplisome that is the source for duplicated
      material in the MCF7 breast tumor cell line.

PMID- 15262809
TI  - Predicting protein-peptide interactions via a network-based motif sampler.
AB  - MOTIVATION: Many protein-protein interactions are mediated by peptide recognition
      modules (PRMs), compact domains that bind to short peptides, and play a critical
      role in a wide array of biological processes. Recent experimental protein
      interaction data provide us with an opportunity to examine whether we may
      explain, or even predict their interactions by computational sequence analysis.
      Such a question was recently posed by the use of random peptide screens to
      characterize the ligands of one such PRM, the SH3 domain. RESULTS: We describe a
      general computational procedure for identifying the ligand peptides of PRMs by
      combining protein sequence information and observed physical interactions into a
      simple probabilistic model and from it derive an interaction-mediated de novo
      motif-finding framework. Using a recent all-versus-all yeast two-hybrid SH3
      domain interaction network, we demonstrate that our technique can be used to
      derive independent predictions of interactions mediated by SH3 domains. We show
      that only when sequence information is combined with such all versus all protein
      interaction datasets, are we capable of identifying motifs with sufficient
      sensitivity and specificity for predicting interactions. The algorithm is general
      so that it may be applied to other PRM domains (e.g. SH2, WW, PDZ). AVAILABILITY:
      The Netmotsa software and source code, as part of a general Gibbs motif sampling
      library, are available at http://sf.net/projects/netmotsa

PMID- 15262810
TI  - Robust inference of groups in gene expression time-courses using mixtures of
      HMMs.
AB  - MOTIVATION: Genetic regulation of cellular processes is frequently investigated
      using large-scale gene expression experiments to observe changes in expression
      over time. This temporal data poses a challenge to classical distance-based
      clustering methods due to its horizontal dependencies along the time-axis. We
      propose to use hidden Markov models (HMMs) to explicitly model these time
      dependencies. The HMMs are used in a mixture approach that we show to be superior
      over clustering. Furthermore, mixtures are a more realistic model of the
      biological reality, as an unambiguous partitioning of genes into clusters of
      unique functional assignment is impossible. Use of the mixture increases
      robustness with respect to noise and allows an inference of groups at varying
      level of assignment ambiguity. A simple approach, partially supervised learning,
      allows to benefit from prior biological knowledge during the training. Our method
      allows simultaneous analysis of cyclic and non-cyclic genes and copes well with
      noise and missing values. RESULTS: We demonstrate biological relevance by
      detection of phase-specific groupings in HeLa time-course data. A benchmark using
      simulated data, derived using assumptions independent of those in our method,
      shows very favorable results compared to the baseline supplied by k-means and two
      prior approaches implementing model-based clustering. The results stress the
      benefits of incorporating prior knowledge, whenever available. AVAILABILITY: A
      software package implementing our method is freely available under the GNU
      general public license (GPL) at http://ghmm.org/gql

PMID- 15262811
TI  - Mining MEDLINE for implicit links between dietary substances and diseases.
AB  - MOTIVATION: Text mining systems aim at knowledge discovery from text collections.
      This work presents our text mining algorithm and demonstrates its use to uncover
      information that could form the basis of new hypotheses. In particular, we use it
      to discover novel uses for Curcuma longa, a dietary substance, which is highly
      regarded for its therapeutic properties in Asia. RESULTS: Several disease were
      identified that offer novel research contexts for curcumin. We analyze select
      suggestions, such as retinal diseases, Crohn's disease and disorders related to
      the spinal cord. Our analysis suggests that there is strong evidence in favor of
      a beneficial role for curcumin in these diseases. The evidence is based on
      curcumin's influence on several genes, such as COX-2, TNF-alpha, JNK, p38 MAPK
      and TGF-beta. This research suggests that our discovery algorithm may be used to
      suggest novel uses for dietary and pharmacological substances. More generally,
      our text mining algorithm may be used to uncover information that potentially
      sheds new light on a given topic of interest. AVAILABILITY: Contact authors.

PMID- 15262812
TI  - Prediction of class I T-cell epitopes: evidence of presence of immunological hot
      spots inside antigens.
AB  - MOTIVATION: Processing and presentation of major histocompatibility complex class
      I antigens to cytotoxic T-lymphocytes is crucial for immune surveillance against
      intracellular bacteria, parasites, viruses and tumors. Identification of
      antigenic regions on pathogen proteins will play a pivotal role in designer
      vaccine immunotherapy. We have developed a system that not only identifies high
      binding T-cell antigenic epitopes, but also class I T-cell antigenic clusters
      termed immunological hot spots. METHODS: MULTIPRED, a computational system for
      promiscuous prediction of HLA class I binders, uses artificial neural networks
      (ANN) and hidden Markov models (HMM) as predictive engines. The models were
      rigorously trained, tested and validated using experimentally identified HLA
      class I T-cell epitopes from human melanoma related proteins and human
      papillomavirus proteins E6 and E7. We have developed a scoring scheme for
      identification of immunological hot spots for HLA class I molecules, which is the
      sum of the highest four predictions within a window of 30 amino acids. RESULTS:
      Our predictions against experimental data from four melanoma-related proteins
      showed that MULTIPRED ANN and HMM models could predict T-cell epitopes with high
      accuracy. The analysis of proteins E6 and E7 showed that ANN models appear to be
      more accurate for prediction of HLA-A3 hot spots and HMM models for HLA-A2
      predictions. For illustration of its utility we applied MULTIPRED for prediction
      of promiscuous T-cell epitopes in all four SARS coronavirus structural proteins.
      MULTIPRED predicted HLA-A2 and HLA-A3 hot spots in each of these proteins.

PMID- 15262813
TI  - Exploring Williams-Beuren syndrome using myGrid.
AB  - MOTIVATION: In silico experiments necessitate the virtual organization of people,
      data, tools and machines. The scientific process also necessitates an awareness
      of the experience base, both of personal data as well as the wider context of
      work. The management of all these data and the co-ordination of resources to
      manage such virtual organizations and the data surrounding them needs significant
      computational infra-structure support. RESULTS: In this paper, we show that
      (my)Grid, middleware for the Semantic Grid, enables biologists to perform and
      manage in silico experiments, then explore and exploit the results of their
      experiments. We demonstrate (my)Grid in the context of a series of bioinformatics
      experiments focused on a 1.5 Mb region on chromosome 7 which is deleted in
      Williams-Beuren syndrome (WBS). Due to the highly repetitive nature of sequence
      flanking/in the WBS critical region (WBSCR), sequencing of the region is
      incomplete leaving documented gaps in the released sequence. (my)Grid was used in
      a series of experiments to find newly sequenced human genomic DNA clones that
      extended into these 'gap' regions in order to produce a complete and accurate map
      of the WBSCR. Once placed in this region, these DNA sequences were analysed with
      a battery of prediction tools in order to locate putative genes and regulatory
      elements possibly implicated in the disorder. Finally, any genes discovered were
      submitted to a range of standard bioinformatics tools for their characterization.
      We report how (my)Grid has been used to create workflows for these in silico
      experiments, run those workflows regularly and notify the biologist when new DNA
      and genes are discovered. The (my)Grid services collect and co-ordinate data
      inputs and outputs for the experiment, as well as much provenance information
      about the performance of experiments on WBS. AVAILABILITY: The (my)Grid software
      is available via http://www.mygrid.org.uk

PMID- 15262814
TI  - Tracking repeats using significance and transitivity.
AB  - MOTIVATION: Internal repeats in coding sequences correspond to structural and
      functional units of proteins. Moreover, duplication of fragments of coding
      sequences is known to be a mechanism to facilitate evolution. Identification of
      repeats is crucial to shed light on the function and structure of proteins, and
      explain their evolutionary past. The task is difficult because during the course
      of evolution many repeats diverged beyond recognition. RESULTS: We introduce a
      new method TRUST, for ab initio determination of internal repeats in proteins. It
      provides an improvement in prediction quality as compared to alternative state-of
      the-art methods. The increased sensitivity and accuracy of the method is achieved
      by exploiting the concept of transitivity of alignments. Starting from
      significant local suboptimal alignments, the application of transitivity allows
      us to (1) identify distant repeat homologues for which no alignments were found;
      (2) gain confidence about consistently well-aligned regions; and (3) recognize
      and reduce the contribution of non-homologous repeats. This re-assessment step
      enables us to derive a virtually noise-free profile representing a generalized
      repeat with high fidelity. We also obtained superior specificity by employing
      rigid statistical testing for self-sequence and profile-sequence alignments.
      Assessment was done using a database of repeat annotations based on structural
      superpositioning. The results show that TRUST is a useful and reliable tool for
      mining tandem and non-tandem repeats in protein sequence databases, capable of
      predicting multiple repeat types with varying intervening segments within a
      single sequence. AVAILABILITY: The TRUST server (together with the source code)
      is available at http://ibivu.cs.vu.nl/programs/trustwww

PMID- 15262815
TI  - Genomic features in the breakpoint regions between syntenic blocks.
AB  - MOTIVATION: We study the largely unaligned regions between the syntenic blocks
      conserved in humans and mice, based on data extracted from the UCSC genome
      browser. These regions contain evolutionary breakpoints caused by inversion,
      translocation and other processes. RESULTS: We suggest explanations for the
      limited amount of genomic alignment in the neighbourhoods of breakpoints. We
      discount inferences of extensive breakpoint reuse as artefacts introduced during
      the reconstruction of syntenic blocks. We find that the number, size and
      distribution of small aligned fragments in the breakpoint regions depend on the
      origin of the neighbouring blocks and the other blocks on the same chromosome. We
      account for this and for the generalized loss of alignment in the regions
      partially by artefacts due to alignment protocols and partially by mutational
      processes operative only after the rearrangement event. These results are
      consistent with breakpoints occurring randomly over virtually the entire genome.

PMID- 15262816
TI  - Learning kernels from biological networks by maximizing entropy.
AB  - MOTIVATION: The diffusion kernel is a general method for computing pairwise
      distances among all nodes in a graph, based on the sum of weighted paths between
      each pair of nodes. This technique has been used successfully, in conjunction
      with kernel-based learning methods, to draw inferences from several types of
      biological networks. RESULTS: We show that computing the diffusion kernel is
      equivalent to maximizing the von Neumann entropy, subject to a global constraint
      on the sum of the Euclidean distances between nodes. This global constraint
      allows for high variance in the pairwise distances. Accordingly, we propose an
      alternative, locally constrained diffusion kernel, and we demonstrate that the
      resulting kernel allows for more accurate support vector machine prediction of
      protein functional classifications from metabolic and protein-protein interaction
      networks. AVAILABILITY: Supplementary results and data are available at
      noble.gs.washington.edu/proj/maxent

PMID- 15262817
TI  - Exploiting conserved structure for faster annotation of non-coding RNAs without
      loss of accuracy.
AB  - MOTIVATION: Non-coding RNAs (ncRNAs)-functional RNA molecules not coding for
      proteins-are grouped into hundreds of families of homologs. To find new members
      of an ncRNA gene family in a large genome database, covariance models (CMs) are a
      useful statistical tool, as they use both sequence and RNA secondary structure
      information. Unfortunately, CM searches are slow. Previously, we introduced
      'rigorous filters', which provably sacrifice none of CMs' accuracy, although
      often scanning much faster. A rigorous filter, using a profile hidden Markov
      model (HMM), is built based on the CM, and filters the genome database,
      eliminating sequences that provably could not be annotated as homologs. The CM is
      run only on the remainder. Some biologically important ncRNA families could not
      be scanned efficiently with this technique, largely due to the significance of
      conserved secondary structure relative to primary sequence in identifying these
      families. Current heuristic filters are also expected to perform poorly on such
      families. RESULTS: By augmenting profile HMMs with limited secondary structure
      information, we obtain rigorous filters that accelerate CM searches for virtually
      all known ncRNA families from the Rfam Database and tRNA models in tRNAscan-SE.
      These filters scan an 8 gigabase database in weeks instead of years, and uncover
      homologs missed by heuristic techniques to speed CM searches. AVAILABILITY:
      Software in development; contact the authors.

PMID- 15262818
TI  - Filtering erroneous protein annotation.
AB  - MOTIVATION: Automatically generated annotation on protein data of UniProt
      (Universal Protein Resource) is planned to be publicly available on the UniProt
      web pages in April 2004. It is expected that the data content of over 500,000
      protein entries in the TrEMBL section will be enhanced by the output of an
      automated annotation pipeline. However, a part of the automatically added data
      will be erroneous, as are parts of the information coming from other sources. We
      present a post-processing system called Xanthippe that is based on a simple
      exclusion mechanism and a decision tree approach using the C4.5 data-mining
      algorithm. RESULTS: It is shown that Xanthippe detects and flags a large part of
      the annotation errors and considerably increases the reliability of both
      automatically generated data and annotation from other sources. As a cross
      validation to Swiss-Prot shows, errors in protein descriptions, comments and
      keywords are successfully filtered out. Xanthippe is a contradictive application
      that can be combined seamlessly with predictive systems. It can be used either to
      improve the precision of automated annotation at a constant level of recall or
      increase the recall at a constant level of precision. AVAILABILITY: The
      application of the Xanthippe rules can be browsed at http://www.ebi.uniprot.org/

PMID- 15262819
TI  - Reconstructing phylogeny by quadratically approximated maximum likelihood.
AB  - Maximum likelihood (ML) for phylogenetic inference from sequence data remains a
      method of choice, but has computational limitations. In particular, it cannot be
      applied for a global search through all potential trees when the number of taxa
      is large, and hence a heuristic restriction in the search space is required. In
      this paper, we derive a quadratic approximation, QAML, to the likelihood function
      whose maximum is easily determined for a given tree. The derivation depends on
      Hadamard conjugation, and hence is limited to the simple symmetric models of
      Kimura and of Jukes and Cantor. Preliminary testing has demonstrated the accuracy
      of QAML is close to that of ML.

PMID- 15262820
TI  - Using MoBIoS' scalable genome join to find conserved primer pair candidates
      between two genomes.
AB  - MOTIVATION: For the purpose of identifying evolutionary reticulation events in
      flowering plants, we determine a large number of paired, conserved DNA oligomers
      that may be used as primers to amplify orthologous DNA regions using the
      polymerase chain reaction (PCR). RESULTS: We develop an initial candidate set by
      comparing the Arabidopsis and rice genomes using MoBIoS (Molecular Biological
      Information System). MoBIoS is a metric-space database management system
      targeting life science data. Through the use of metric-space indexing techniques,
      two genomes can be compared in O(mlog n), where m and n are the lengths of the
      genomes, versus O(mn) for BLAST-based analysis. The filtering of low-complexity
      regions may also be accomplished by directly assessing the uniqueness of the
      region. We describe mSQL, a SQL extension being developed for MoBIoS that
      encapsulates the algorithmic details in a common database programming language,
      shielding end-users from esoteric programming. AVAILABILITY: Available upon
      request from authors.

PMID- 15262821
TI  - Protein network inference from multiple genomic data: a supervised approach.
AB  - MOTIVATION: An increasing number of observations support the hypothesis that most
      biological functions involve the interactions between many proteins, and that the
      complexity of living systems arises as a result of such interactions. In this
      context, the problem of inferring a global protein network for a given organism,
      using all available genomic data about the organism, is quickly becoming one of
      the main challenges in current computational biology. RESULTS: This paper
      presents a new method to infer protein networks from multiple types of genomic
      data. Based on a variant of kernel canonical correlation analysis, its
      originality is in the formalization of the protein network inference problem as a
      supervised learning problem, and in the integration of heterogeneous genomic data
      within this framework. We present promising results on the prediction of the
      protein network for the yeast Saccharomyces cerevisiae from four types of widely
      available data: gene expressions, protein interactions measured by yeast two
      hybrid systems, protein localizations in the cell and protein phylogenetic
      profiles. The method is shown to outperform other unsupervised protein network
      inference methods. We finally conduct a comprehensive prediction of the protein
      network for all proteins of the yeast, which enables us to propose protein
      candidates for missing enzymes in a biosynthesis pathway. AVAILABILITY: Softwares
      are available upon request.

PMID- 15262822
TI  - A two-stage classifier for identification of protein-protein interface residues.
AB  - MOTIVATION: The ability to identify protein-protein interaction sites and to
      detect specific amino acid residues that contribute to the specificity and
      affinity of protein interactions has important implications for problems ranging
      from rational drug design to analysis of metabolic and signal transduction
      networks. RESULTS: We have developed a two-stage method consisting of a support
      vector machine (SVM) and a Bayesian classifier for predicting surface residues of
      a protein that participate in protein-protein interactions. This approach
      exploits the fact that interface residues tend to form clusters in the primary
      amino acid sequence. Our results show that the proposed two-stage classifier
      outperforms previously published sequence-based methods for predicting interface
      residues. We also present results obtained using the two-stage classifier on an
      independent test set of seven CAPRI (Critical Assessment of PRedicted
      Interactions) targets. The success of the predictions is validated by examining
      the predictions in the context of the three-dimensional structures of protein
      complexes.

PMID- 15262823
TI  - IMGT/JunctionAnalysis: the first tool for the analysis of the immunoglobulin and
      T cell receptor complex V-J and V-D-J JUNCTIONs.
AB  - MOTIVATION: To create the enormous diversity of 10(12) immunoglobulins (IG) and T
      cell receptors (TR) per individual, very complex mechanisms occur at the DNA
      level: the combinatorial diversity results from the junction of the variable (V),
      diversity (D) and joining (J) genes; the N-diversity represents the addition at
      random of nucleotides not encoded in the genome; and somatic hypermutations occur
      in IG rearranged sequences. The accurate annotation of the junction between V, D,
      J genes in rearranged IG and TR sequences represents therefore a huge challenge
      by its uniqueness and complexity. We developed IMGT/JunctionAnalysis to analyse
      automatically in detail the IG and TR junctions, according to the IMGT Scientific
      chart rules, based on the IMGT-ONTOLOGY concepts. RESULTS: IMGT/JunctionAnalysis
      is the first tool for the detailed analysis of the IG and TR complex V-J and V-D
      J JUNCTION(s). It delimits, at the nucleotide level, the genes resulting from the
      combinatorial diversity. It identifies accurately the D genes in the junctions of
      IG heavy (IGH), TR beta (TRB) and delta (TRD) chains. It delimits the palindromic
      P-REGION(s) and the N-REGION(s) resulting from the N-diversity. It evaluates the
      number of somatic hypermutations for each gene, within the JUNCTION.
      IMGT/JunctionAnalysis is capable of analysing, in a single run, an unlimited
      number of junctions from the same species (currently human or mouse) and from the
      same locus. AVAILABILITY: IMGT/JunctionAnalysis is available from the IMGT Home
      page at http://imgt.cines.fr

PMID- 15262824
TI  - Predicting protein folding pathways.
AB  - A structured folding pathway, which is a time ordered sequence of folding events,
      plays an important role in the protein folding process and hence, in the
      conformational search. Pathway prediction, thus gives more insight into the
      folding process and is a valuable guiding tool to search the conformation space.
      In this paper, we propose a novel 'unfolding' approach to predict the folding
      pathway. We apply graph-based methods on a weighted secondary structure graph of
      a protein to predict the sequence of unfolding events. When viewed in reverse
      this yields the folding pathway. We demonstrate the success of our approach on
      several proteins whose pathway is partially known.

PMID- 15262826
TI  - Fish intake and risk of incident atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in clinical
      practice and is particularly common in the elderly. Although effects of fish
      intake, including potential antiarrhythmic effects, may favorably influence risk
      of AF, relationships between fish intake and AF incidence have not been
      evaluated. METHODS AND RESULTS: In a prospective, population-based cohort of 4815
      adults > or =age 65 years, usual dietary intake was assessed at baseline in 1989
      and 1990. Consumption of tuna and other broiled or baked fish correlated with
      plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish
      or fish sandwiches (fish burgers) did not. AF incidence was prospectively
      ascertained on the basis of hospital discharge records and annual
      electrocardiograms. During 12 years' follow-up, 980 cases of incident AF were
      diagnosed. In multivariate analyses, consumption of tuna or other broiled or
      baked fish was inversely associated with incidence of AF, with 28% lower risk
      with intake 1 to 4 times per week (HR=0.72, 95% CI=0.58 to 0.91, P=0.005), and
      31% lower risk with intake > or =5 times per week (HR=0.69, 95% CI=0.52 to 0.91,
      P=0.008), compared with <1 time per month (P trend=0.004). Results were not
      materially different after adjustment for preceding myocardial infarction or
      congestive heart failure. In similar analyses, fried fish/fish sandwich
      consumption was not associated with lower risk of AF. CONCLUSIONS: Among elderly
      adults, consumption of tuna or other broiled or baked fish, but not fried fish or
      fish sandwiches, is associated with lower incidence of AF. Fish intake may
      influence risk of this common cardiac arrhythmia.

PMID- 15262827
TI  - Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by
      intravenous aprotinin during cardiothoracic surgery.
AB  - BACKGROUND: Protease-activated receptor-1 (PAR1) is the principal thrombin
      receptor in the vasculature, and antagonists against this receptor are in
      preclinical trials. Aprotinin, already approved for clinical use to reduce
      transfusion requirements in cardiopulmonary bypass (CPB) surgery, has been shown
      to inhibit PAR1 activation in vitro. Here, we exploit CPB as a model for thrombin
      generation in humans to examine whether aprotinin can inhibit platelet PAR1
      activation clinically. METHODS AND RESULTS: PAR1 expression and function on
      platelets was examined in coronary artery bypass grafting (CABG) patients
      randomized into 2 groups: (1) those receiving saline infusion during CPB (n=17)
      and (2) those receiving aprotinin (2x10(6) kallikrein inhibitor units [KIU] in
      pump prime, 2x10(6) KIU loading dose, followed by 0.5x10(6) KIU/h [n=13]).
      Platelets in the saline group showed loss of PAR1-specific function at 2 hours
      after CPB, but this was preserved in the aprotinin group (P<0.001). These effects
      were most likely targeted at PAR1 receptor cleavage, because (1) the level of
      thrombin generated during CPB did not vary significantly between groups, (2)
      expression of SPAN12, which detects only uncleaved PAR1 receptors, was preserved
      in the aprotinin but not the placebo group (P<0.05), and (3) supporting evidence
      in vitro showed reduced thrombin-induced PAR1 cleavage (P<0.001) and platelet
      aggregation (P<0.001) in the presence of aprotinin. CONCLUSIONS: This study
      demonstrates that platelet PAR1 activation by thrombin can be inhibited by
      aprotinin. Our results extend the clinical mechanism of action of aprotinin and
      provide the first proof of principle that PAR1 can be inhibited clinically. This
      has implications beyond cardiac surgery for the development of therapeutic PAR1
      blockade.

PMID- 15262828
TI  - Loading with 600 mg clopidogrel in patients with coronary artery disease with and
      without chronic clopidogrel therapy.
AB  - BACKGROUND: It is not known whether further suppression of platelet function can
      be achieved with clopidogrel beyond that provided by currently recommended
      loading and maintenance doses. We performed a comparative assessment of the
      antiplatelet effects of a 600-mg loading dose of clopidogrel given to patients
      with and without chronic clopidogrel therapy. METHODS AND RESULTS: Those eligible
      for this prospective study were aspirin-treated patients with suspected or
      documented coronary artery disease admitted to hospital for coronary angiography.
      Two series of 20 consecutive patients each were assessed in this study. The first
      series included patients who had never received clopidogrel (first-use group);
      the second series included patients on chronic therapy with a daily dose of 75 mg
      clopidogrel for > or =1 month (chronic therapy group). Blood samples were drawn
      before and 6 hours after oral administration of 600 mg clopidogrel for
      aggregometry and flow cytometry studies. In the first-use group, loading with 600
      mg clopidogrel inhibited ADP 5 micromol/L-induced platelet aggregation from 90+/
      9% to 51+/-19% (P<0.001). In the chronic therapy group, loading with 600 mg
      clopidogrel yielded further inhibition of ADP 5 micromol/L-induced platelet
      aggregation in addition to that achieved by the maintenance dose of 75 mg/d, from
      52+/-14% to 33+/-12% (P<0.001). In both groups, 600 mg clopidogrel loading
      significantly inhibited ADP-induced expression of glycoprotein IIb/IIIa and P
      selectin receptors. CONCLUSIONS: Further platelet inhibition can be achieved with
      clopidogrel in addition to that provided by currently recommended loading and
      maintenance doses. Higher doses may be warranted after assessment of their
      clinical efficacy and safety.

PMID- 15262829
TI  - Gene therapy of endothelial nitric oxide synthase and manganese superoxide
      dismutase restores delayed wound healing in type 1 diabetic mice.
AB  - BACKGROUND: Nitric oxide (NO) deficiency contributes to diabetic wound healing
      impairment. The present study tested the hypothesis that increased cutaneous
      superoxide (O2-) levels in type 1 diabetic mice cause NO deficiency and delayed
      wound healing. METHODS AND RESULTS: Wound healing was markedly delayed in
      streptozotocin-induced type 1 diabetic mice compared with the normal controls.
      There were significantly reduced levels of endothelial NO synthase (eNOS) protein
      and constitutive NOS activity in diabetic wounds, whereas O2- levels were
      markedly increased. A single regimen of cutaneous gene therapy of eNOS or
      manganese superoxide dismutase (MnSOD) restored such healing delay, with a
      concomitant suppression of wound O2- levels and augmentation of both eNOS protein
      and constitutive NOS activity. Gene therapy of MnSOD also increased cutaneous
      MnSOD activity. Cutaneous O2- levels were also increased in Ins2(Akita) diabetic
      mice. In vitro glucose treatment of cutaneous tissues from normal mice for 24
      hours increased O2- levels in a concentration-dependent manner. The enhanced
      cutaneous O2- levels induced by high glucose in both normal and diabetic mice
      were abolished by the NADPH oxidase inhibitor apocynin and the protein kinase C
      inhibitor chelerythrine. Furthermore, ex vivo gene transfer of dominant-negative
      HA-tagged N17Rac1, which inhibits NADPH oxidase subunit Rac1, significantly
      inhibited cutaneous O2- formation induced by high glucose in both normal and
      Ins2(Akita) diabetic mice. CONCLUSIONS: These results indicate that hyperglycemia
      augments cutaneous O2- levels, at least in part, via NADPH oxidase and protein
      kinase C pathways, resulting in impaired wound healing in type 1 diabetic mice.
      Gene therapy strategies aimed at restoring cutaneous NO bioavailability may
      provide an effective means to ameliorate delayed diabetic wound healing.

PMID- 15262830
TI  - Prevalence of and risk factors for peripheral arterial disease in the United
      States: results from the National Health and Nutrition Examination Survey, 1999
      2000.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is associated with significant
      morbidity and mortality and is an important marker of subclinical coronary heart
      disease. However, estimates of PAD prevalence in the general US population have
      varied widely. METHODS AND RESULTS: We analyzed data from 2174 participants aged
      40 years and older from the 1999-2000 National Health and Nutrition Examination
      Survey. PAD was defined as an ankle-brachial index <0.90 in either leg. The
      prevalence of PAD among adults aged 40 years and over in the United States was
      4.3% (95% CI 3.1% to 5.5%), which corresponds to approximately 5 million
      individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the
      prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted
      logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42)
      current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to
      7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR
      1.68, 95% CI 1.09 to 2.57), and low kidney function (OR 2.00, 95% CI 1.08 to
      3.70) were positively associated with prevalent PAD. More than 95% of persons
      with PAD had 1 or more cardiovascular disease risk factors. Elevated fibrinogen
      and C-reactive protein levels were also associated with PAD. CONCLUSIONS: This
      study provides nationally representative prevalence estimates of PAD in the
      United States, revealing that PAD affects more than 5 million adults. PAD
      prevalence increases dramatically with age and disproportionately affects blacks.
      The vast majority of individuals with PAD have 1 or more cardiovascular disease
      risk factors that should be targeted for therapy.

PMID- 15262831
TI  - Acyl-coenzyme A:cholesterol acyltransferase inhibition ameliorates proteinuria,
      hyperlipidemia, lecithin-cholesterol acyltransferase, SRB-1, and low-denisty
      lipoprotein receptor deficiencies in nephrotic syndrome.
AB  - BACKGROUND: Nephrotic syndrome (NS) is associated with hyperlipidemia, altered
      lipid regulatory enzymes and receptors, and increased risk of progressive renal
      and cardiovascular diseases. Acyl-coenzyme A:cholesterol acyltransferase (ACAT)
      catalyzes intracellular esterification of cholesterol and plays an important role
      in production of apolipoprotein B-containing lipoproteins, regulation of
      cholesterol-responsive proteins, and formation of foam cells. Because hepatic
      ACAT-2 is markedly upregulated in NS, we tested the hypothesis that inhibition of
      ACAT may improve cholesterol metabolism in NS. METHODS AND RESULTS: Rats with
      puromycin-induced NS were treated with either the ACAT inhibitor CI-976 or
      placebo for 2 weeks. Normal rats served as controls. Plasma lipids, renal
      function, and key lipid regulatory factors were measured. Untreated NS rats
      showed heavy proteinuria; hypoalbuminemia; elevated plasma cholesterol,
      triglyceride, LDL, VLDL, and total cholesterol-to-HDL cholesterol ratio;
      increased hepatic ACAT activity, ACAT-2 mRNA, and ACAT-2 protein; and reduced LDL
      receptor, HDL receptor, otherwise known as scavenger receptor B-1 (SRB-1) and
      plasma lecithin-cholesterol acyltransferase (LCAT). ACAT inhibitor reduced plasma
      cholesterol and triglycerides, normalized total cholesterol-to-HDL cholesterol
      ratio, and lowered hepatic ACAT activity without changing ACAT-2 mRNA or protein.
      This was accompanied by near normalizations of plasma LCAT, hepatic SRB-1, and
      LDL receptor and a significant amelioration of proteinuria and hypoalbuminemia.
      CONCLUSIONS: Pharmacological inhibition of ACAT reverses NS-induced LDL receptor,
      HDL receptor, and LCAT deficiencies; improves plasma lipid profile; and
      ameliorates proteinuria in nephrotic animals. Further studies are needed to
      explore the effect of ACAT inhibition in nephrotic humans.

PMID- 15262832
TI  - Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice
      protects against ischemic-reperfusion damage.
AB  - BACKGROUND: Mitochondrial respiration is the main source of energy in aerobic
      animal cells and is adapted to the energy demand by respiratory coupling.
      Uncoupling proteins (UCPs) perturb respiratory coupling by inducing a proton leak
      through the mitochondrial inner membrane. Although this could lead to deleterious
      energy waste, it may prevent the production of oxygen radicals when the rate of
      phosphorylation of ADP into ATP is low, whereas oxygen and substrate availability
      to mitochondria is high. The latter conditions are encountered during cardiac
      reperfusion after ischemia and are highly relevant to heart infarction. METHODS
      AND RESULTS: Heart function of 6 transgenic mice expressing high amounts of UCP1
      and of 6 littermate controls was compared in isolated perfused hearts in
      normoxia, after 40-minute global ischemia, and on reperfusion. In normoxia,
      oxygen consumption, contractility (quantified as the rate-pressure product), and
      their relationship (energetic yield) were similar in controls and transgenic
      mice. Although UCP1 expression did not alter the sensitivity to ischemia, it
      significantly improved functional recovery on reperfusion. After 60 minutes of
      reperfusion, contractility was 2-fold higher in transgenic mice than in controls.
      Oxygen consumption remained significantly depressed in controls (53+/-27% of
      control), whereas it recovered strikingly to preischemic values in transgenic
      mice, showing uncoupling of respiration by UCP1 activity. Glutathione and
      aconitase, markers of oxidative damage, indicated lower oxidative stress in
      transgenic mice. CONCLUSIONS: UCP1 activity is low under normoxia but is induced
      during ischemia-reperfusion. The presence of UCP1 mitigates reperfusion-induced
      damage, probably because it lowers mitochondrial hyperpolarization at
      reperfusion.

PMID- 15262833
TI  - Effect of atorvastatin on risk of recurrent cardiovascular events after an acute
      coronary syndrome associated with high soluble CD40 ligand in the Myocardial
      Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study.
AB  - BACKGROUND: Patients with acute coronary syndromes have elevated plasma levels of
      the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit
      CD40L signaling in vitro, but there are no prospective studies of statins and
      sCD40L in acute coronary syndromes. METHODS AND RESULTS: We measured sCD40L in
      subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia
      Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were
      randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16
      weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and
      2352 (76%) at 16 weeks. Odds ratios (ORs) and 95% CIs from logistic regression
      models assessed the risk of recurrent cardiovascular events over 16 weeks (death,
      nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring
      rehospitalization) in the placebo group from baseline sCD40L and the effect of
      atorvastatin on the risk associated with CD40L in all subjects. The effects of
      atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests.
      There was a threshold effect, with only high sCD40L (>90th centile) being a risk
      factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This
      risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced
      the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0.08).
      CONCLUSIONS: In patients with acute coronary syndromes, atorvastatin abrogated
      the risk of recurrent cardiovascular events associated with high sCD40L. Early
      statin therapy after acute coronary syndromes counters the risk associated with
      elevated sCD40L.

PMID- 15262834
TI  - C-reactive protein, the metabolic syndrome, and prediction of cardiovascular
      events in the Framingham Offspring Study.
AB  - BACKGROUND: Inflammation (assessed by C-reactive protein [CRP]) and the metabolic
      syndrome (MetS) are associated with cardiovascular disease (CVD), but population
      based data are limited. METHODS AND RESULTS: We assessed the cross-sectional
      relations of CRP to the MetS (National Cholesterol Education Program Expert Panel
      on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults,
      Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54
      years) and the utility of CRP and the MetS to predict new CVD events (n=189) over
      7 years. MetS (> or =3 of 5 traits) was present in 24% of subjects; mean age
      adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5,
      4.2, 6.0, or 6.6 mg/L, respectively (P trend <0.0001). In persons with MetS, age
      adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L;
      P<0.0001). MetS and baseline CRP were individually related to CVD events (for
      MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest
      versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD
      persisted for MetS and CRP even after adjustment in a model including age, sex,
      MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c
      statistic associated with the age- and sex-adjusted model including CRP was 0.72;
      including MetS, 0.74; and including CRP and MetS, 0.74. CONCLUSIONS: Elevated CRP
      levels are related to insulin resistance and the presence of the MetS, especially
      in women. Although discrimination of subjects at risk of CVD events using both
      MetS and CRP is not better than using either phenotype alone, both CRP and MetS
      are independent predictors of new CVD events.

PMID- 15262835
TI  - TIMP-3 deficiency leads to dilated cardiomyopathy.
AB  - BACKGROUND: Despite the mounting clinical burden of heart failure, the
      biomolecules that control myocardial tissue remodeling are poorly understood.
      TIMP-3 is an endogenous inhibitor of matrix metalloproteinases (MMPs) that has
      been found to be deficient in failing human myocardium. We hypothesized that TIMP
      3 expression prevents maladaptive tissue remodeling in the heart, and
      accordingly, its deficiency in mice would alone be sufficient to trigger
      progressive cardiac remodeling and dysfunction similar to human heart failure.
      METHODS AND RESULTS: Mice with a targeted timp-3 deficiency were evaluated with
      aging and compared with age-matched wild-type littermates. Loss of timp-3
      function triggered spontaneous LV dilatation, cardiomyocyte hypertrophy, and
      contractile dysfunction at 21 months of age consistent with human dilated
      cardiomyopathy. Its absence also resulted in interstitial matrix disruption with
      elevated MMP-9 activity, and activation of the proinflammatory tumor necrosis
      factor-alpha cytokine system, molecular hallmarks of human myocardial remodeling.
      CONCLUSIONS: TIMP-3 deficiency disrupts matrix homeostasis and the balance of
      inflammatory mediators, eliciting the transition to cardiac dilation and
      dysfunction. Therapeutic restoration of myocardial TIMP-3 may provide a novel
      approach to limit cardiac remodeling and the progression to failure in patients
      with dilated cardiomyopathy.

PMID- 15262836
TI  - Thrombolysis compared with heparin for the initial treatment of pulmonary
      embolism: a meta-analysis of the randomized controlled trials.
AB  - BACKGROUND: Randomized trials and meta-analyses have reached conflicting
      conclusions about the role of thrombolytic therapy for the treatment of acute
      pulmonary embolism. METHODS AND RESULTS: We performed a meta-analysis of all
      randomized trials comparing thrombolytic therapy with heparin in patients with
      acute pulmonary embolism. Eleven trials, involving 748 patients, were included.
      Compared with heparin, thrombolytic therapy was associated with a nonsignificant
      reduction in recurrent pulmonary embolism or death (6.7% versus 9.6%; OR 0.67,
      95% CI 0.40 to 1.12, P for heterogeneity=0.48), a nonsignificant increase in
      major bleeding (9.1% versus 6.1%; OR 1.42, 95% CI 0.81 to 2.46), and a
      significant increase in nonmajor bleeding (22.7% versus 10.0%; OR 2.63, 95% CI
      1.53 to 4.54; number needed to harm=8). Thrombolytic therapy compared with
      heparin was associated with a significant reduction in recurrent pulmonary
      embolism or death in trials that also enrolled patients with major
      (hemodynamically unstable) pulmonary embolism (9.4% versus 19.0%; OR 0.45, 95% CI
      0.22 to 0.92; number needed to treat=10) but not in trials that excluded these
      patients (5.3% versus 4.8%; OR 1.07, 95% CI 0.50 to 2.30), with significant
      heterogeneity between these 2 groups of trials (P=0.10). CONCLUSIONS: Currently
      available data provide no evidence for a benefit of thrombolytic therapy compared
      with heparin for the initial treatment of unselected patients with acute
      pulmonary embolism. A benefit is suggested in those at highest risk of recurrence
      or death. The number of patients enrolled in randomized trials to date is modest,
      and further evaluation of the efficacy and safety of thrombolytic therapy for the
      treatment of high-risk patients with acute pulmonary embolism appears warranted.

PMID- 15262837
TI  - Risk factors and recurrence rate of primary deep vein thrombosis of the upper
      extremities.
AB  - BACKGROUND: One third of cases of upper-extremity deep vein thrombosis (DVT) are
      primary, ie, they occur in the absence of central venous catheters or cancer.
      Risk factors for primary upper-extremity DVT are not well established, and the
      recurrence rate is unknown. METHODS AND RESULTS: We studied 115 primary upper
      extremity DVT patients and 797 healthy controls for the presence of thrombophilia
      due to factor V Leiden, prothrombin G20210A, antithrombin, protein C, protein S
      deficiency, and hyperhomocysteinemia. Transient risk factors for venous
      thromboembolism were recorded. Recurrent upper-extremity DVT was evaluated
      prospectively over a median of 5.1 years of follow-up. The adjusted odds ratio
      for upper-extremity DVT was 6.2 (95% CI 2.5 to 15.7) for factor V Leiden, 5.0
      (95% CI 2.0 to 12.2) for prothrombin G20210A, and 4.9 (95% CI 1.1 to 22.0) for
      the anticoagulant protein deficiencies. Hyperhomocysteinemia and oral
      contraceptives were not associated with upper-extremity DVT. However, in women
      with factor V Leiden or prothrombin G20210A who were taking oral contraceptives,
      the odds ratio for upper-extremity DVT was increased up to 13.6 (95% CI 2.7 to
      67.3). The recurrence rate was 4.4% patient-years in patients with thrombophilia
      and 1.6% patient-years in those without thrombophilia. The hazard ratio for
      recurrent upper-extremity DVT in patients with thrombophilia compared with those
      without was 2.7 (95% CI 0.7 to 9.8). CONCLUSIONS: Inherited thrombophilia is
      associated with an increased risk of upper-extremity DVT. Oral contraceptives
      increase the risk only when combined with inherited thrombophilia. The recurrence
      rate of primary upper-extremity DVT is low but tends to be higher in patients
      with thrombophilia than in those without.

PMID- 15262838
TI  - Association between platelet receptor occupancy after eptifibatide (integrilin)
      therapy and patency, myocardial perfusion, and ST-segment resolution among
      patients with ST-segment-elevation myocardial infarction: an INTEGRITI
      (Integrilin and Tenecteplase in Acute Myocardial Infarction) substudy.
AB  - BACKGROUND: Paradoxically, fibrinolytic agents may systemically activate
      platelets, which in turn secrete plasminogen activator inhibitor (PAI-1), an
      antagonist of the fibrinolytic process in proportion to total body platelet mass.
      We hypothesized that improved epicardial patency, myocardial perfusion, and ST
      segment resolution would be associated with higher levels of platelet receptor
      occupancy (RO) by a glycoprotein IIb/IIIa antagonist in ST-elevation MI (STEMI).
      METHODS AND RESULTS: Patients were drawn from the low-dose tenecteplase plus
      eptifibatide arm of the INTEGRITI study. Angiographic and platelet RO data were
      analyzed at 2 independent core laboratories. To take into account the absolute
      platelet count and receptors available for cross-linking, absolute platelet count
      was multiplied by percent of available receptors to obtain the index of the
      absolute number of receptors available (IANRA). Percent RO was higher among
      patients with a patent artery (TIMI flow grade 2/3; 78.2+/-9.2, n=63 versus
      63.9+/-29.7, n=7; P=0.005), those with TIMI myocardial perfusion grade 2/3
      (79.6+/-9.5, n=40 versus 73.0+/-16.2, n=30; P=0.036), and those with complete (>
      or =70%) ST-segment resolution at 60 minutes (81.3+/-8.3%, n=27 versus 73.1+/
      17.4%, n=24; P=0.034). The absolute number of glycoprotein IIb/IIIa receptors
      available for cross-linking was reduced (ie, the IANRA was lower) among patients
      with a patent artery (P=0.0015), patients with TIMI myocardial perfusion grade
      2/3 (P=0.026), and patients with > or =70% ST-segment resolution (P=0.029).
      CONCLUSIONS: This study links restoration of epicardial flow, normal myocardial
      perfusion, and complete ST-segment resolution with higher levels of platelet
      glycoprotein IIb/IIIa receptor occupancy after therapy with eptifibatide
      administered with tenecteplase.

PMID- 15262839
TI  - Celiprolol, a vasodilatory beta-blocker, inhibits pressure overload-induced
      cardiac hypertrophy and prevents the transition to heart failure via nitric oxide
      dependent mechanisms in mice.
AB  - BACKGROUND: The blockade of beta-adrenergic receptors reduces both mortality and
      morbidity in patients with chronic heart failure, but the cellular mechanism
      remains unclear. Celiprolol, a selective beta(1)-blocker, was reported to
      stimulate the expression of endothelial NO synthase (eNOS) in the heart, and NO
      levels have been demonstrated to be related to myocardial hypertrophy and heart
      failure. Thus, we aimed to clarify whether celiprolol attenuates both myocardial
      hypertrophy and heart failure via the NO-signal pathway. METHODS AND RESULTS: In
      rat neonatal cardiac myocytes, celiprolol inhibited protein synthesis stimulated
      by either isoproterenol or phenylephrine, which was partially suppressed by N(G)
      nitro-L-arginine methyl ester (L-NAME). Four weeks after transverse aortic
      constriction (TAC) in C57BL/6 male mice, the ratio of heart weight to body weight
      (mg/g) (8.70+/-0.42 in TAC, 6.61+/-0.44 with celiprolol 100 mg x kg(-1) x d(-1)
      PO, P<0.01) and the ratio of lung weight to body weight (mg/g) (10.27+/-1.08 in
      TAC, 7.11+/-0.70 with celiprolol 100 mg x kg(-1) x d(-1) PO, P<0.05) were lower
      and LV fractional shortening was higher in the celiprolol-treated groups than in
      the TAC group. All of these improvements were blunted by L-NAME. Celiprolol
      treatment significantly increased myocardial eNOS and activated phosphorylation
      of eNOS. Myocardial mRNA levels of natriuretic peptide precursor type B and
      protein inhibitor of NO synthase, which were increased in the TAC mice, were
      decreased in the celiprolol-treated mice. CONCLUSIONS: These findings indicated
      that celiprolol attenuates cardiac myocyte hypertrophy both in vitro and in vivo
      and halts the process leading from hypertrophy to heart failure. These effects
      are mediated by a selective beta1-adrenergic receptor blockade and NO-dependent
      pathway.

PMID- 15262840
TI  - Cardiac memory evolves with age in association with development of the transient
      outward current.
AB  - BACKGROUND: Calcium-insensitive transient outward current (I(to)) is important to
      the development of cardiac memory (CM), which itself reflects the capacity of the
      heart to remodel electrophysiologically. We used cardiac pacing to test the
      hypothesis that CM evolution can be explained by developmental maturation of
      I(to). METHODS AND RESULTS: Acutely anesthetized dogs from 1 day old to adult
      were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12)
      to induce CM. T-wave vector displacement (TVD) obtained during VP was greater
      than with AP (adults, 0.39+/-0.06 mV; neonates, 0.04+/-0.01 mV; P<0.05). TVD
      began to increase at approximately 40 days of age, reaching adult levels by
      approximately 200 days. Microelectrode studies performed in 18 dogs (ages 3 to 94
      days) after completing the CM protocol and 20 additional dogs (1 day old to
      adult) revealed that the epicardial action potential notch was absent in
      neonates, became apparent in the young, and was deepest in adults. The
      relationship between TVD and epicardial notch was such that as notch magnitude
      increased, TVD increased (r=-0.65, P<0.05). KChIP2 and Kv4.3 mRNA (measured via
      reverse transcription-polymerase chain reaction) also increased with age.
      CONCLUSIONS: The inducibility of CM gradually increases with age in association
      with evolution of the epicardial action potential notch and mRNA expression for
      KChIP2 and Kv4.3. This suggests that the capacity of the heart to remodel
      electrophysiologically and to manifest memory during development depends in part
      on evolution of the determinants of I(to).

PMID- 15262841
TI  - Transcatheter device closure of congenital and postoperative residual ventricular
      septal defects.
AB  - BACKGROUND: Our purpose was to describe a 13-year experience with patients
      undergoing transcatheter device closure of unrepaired congenital or postoperative
      residual ventricular septal defects (VSDs). METHODS AND RESULTS: Since 1989, 170
      patients (median age, 3.9 years) have undergone catheterization for closure of 1
      or more congenital (n=92) or postoperative (n=78) residual VSDs using successive
      generations of STARFlex-type devices. Outcomes included echocardiographic
      assessment of residual flow and device position, assessment of VSD
      shunt/severity, and adverse events. Among 168 patients in whom device
      implantation was performed, between 1 and 7 devices were placed per patient
      (median, 1), with multiple devices placed in 40%. There was a significant
      decrease in left-to-right shunting after device implantation (P<0.001) and
      significant improvement in VSD size/severity, and device position proved stable.
      Of 332 adverse events, 39 were related to the device and 261 were related to the
      catheterization; all but 5 occurred in the periprocedural period. At a median
      follow-up of 24 months (0 to 154 months), 14 patients had died and 18 had
      device(s) explanted. CONCLUSIONS: Congenital and postoperative VSD closure using
      STARFlex-type devices resulted in stable improvement in clinical status and
      decreased interventricular shunting. Although periprocedural events occurred
      frequently, late events caused by the device were rare. Transcatheter device
      closure is an effective management option for patients with complex muscular VSDs
      that are difficult to approach surgically and for postoperative residual VSDs.

PMID- 15262842
TI  - Temporal trends in coronary heart disease mortality and sudden cardiac death from
      1950 to 1999: the Framingham Heart Study.
AB  - BACKGROUND: Throughout the past 50 years, heart disease has been the leading
      cause of death in the United States. Although declines in coronary heart disease
      (CHD) mortality have been noted, there is still uncertainty about the magnitude
      of the decline and whether the trend is similar for sudden cardiac death (SCD).
      METHODS AND RESULTS: We examined temporal trends in SCD and nonsudden CHD death
      in the Framingham Heart Study original and offspring cohorts from 1950 to 1999.
      SCD was defined as a death attributed to CHD with preceding symptoms that lasted
      less than 1 hour; all deaths were adjudicated by a physician panel. Log-linear
      Poisson regression was used to estimate CHD mortality and SCD risk ratios (RRs);
      RRs were adjusted for age and gender. There were 811 CHD deaths: 453 nonsudden
      and 358 SCDs. Ninety-one (20%) of nonsudden CHD deaths and 173 (48%) of SCDs were
      in subjects free of antecedent CHD. From 1950-1969 to 1990-1999, overall CHD
      death rates decreased by 59% (95% CI 47% to 68%, P(trend)<0.001). Nonsudden CHD
      death decreased by 64% (95% CI 50% to 74%, P(trend)<0.001), and SCD rates
      decreased by 49% (95% CI 28% to 64%, P(trend)<0.001). These trends were seen in
      men and women, in subjects with and without a prior history of CHD, and in
      smokers and nonsmokers. CONCLUSIONS: The risks of SCD and nonsudden CHD mortality
      have decreased by 49% to 64% over the past 50 years. These trends were evident in
      subjects with and without heart disease, which suggests important contributions
      of primary and secondary prevention to the decreasing risk of CHD death and SCD.

PMID- 15262843
TI  - Prognostic value of health status in patients with heart failure after acute
      myocardial infarction.
AB  - BACKGROUND: Disease-specific health status instruments such as the Kansas City
      Cardiomyopathy Questionnaire (KCCQ) can quantify symptoms, functional
      limitations, and quality of life in patients with heart failure. Understanding
      the relationship between KCCQ scores and prognosis may assist clinicians in both
      interpreting KCCQ scores and stratifying risk in patients. METHODS AND RESULTS:
      We examined the prognostic value of the KCCQ in a prospective, international
      cohort of 1516 patients with heart failure after a recent acute myocardial
      infarction. We focused on the relationship between the KCCQ overall score (KCCQ
      os), measured at the first outpatient visit (4 weeks after enrollment), and
      subsequent 1-year cardiovascular mortality or hospitalization (n=258, 20.3%).
      KCCQ-os was strongly associated with subsequent cardiovascular events in that
      those with a score > or =75 had an 84% 1-year event-free survival compared with
      59% for those with a score <25 (P<0.001). After demographic and other clinical
      characteristics were controlled for in multivariable models, KCCQ-os remained
      strongly associated with outcome (hazard ratio, 2.02; 95% CI, 1.24 to 3.27 for
      KCCQ-os <25; P<0.001). CONCLUSIONS: In outpatients with heart failure
      complicating an acute myocardial infarction, KCCQ-os is strongly associated with
      subsequent 1-year cardiovascular mortality and hospitalization. Use of the KCCQ
      in outpatient clinical practice can both quantify patients' health status and
      provide insight into their prognosis.

PMID- 15262844
TI  - Cost-effectiveness of sirolimus-eluting stents for treatment of complex coronary
      stenoses: results from the Sirolimus-Eluting Balloon Expandable Stent in the
      Treatment of Patients With De Novo Native Coronary Artery Lesions (SIRIUS) trial.
AB  - BACKGROUND: Recently, sirolimus-eluting stents (SESs) have been shown to
      dramatically reduce the risk of angiographic and clinical restenosis compared
      with bare metal stent (BMS) implantation. However, the overall cost-effectiveness
      of this strategy is unknown. METHODS AND RESULTS: Between February and August
      2001, 1058 patients with complex coronary stenoses were enrolled in the SIRIUS
      trial and randomized to percutaneous coronary revascularization with either a SES
      or BMS. Clinical outcomes, resource use, and costs were assessed prospectively
      for all patients over a 1-year follow-up period. Initial hospital costs were
      increased by 2881 dollars per patient with SESs. Over the 1-year follow-up
      period, use of SESs led to substantial reductions in the need for repeat
      revascularization, including repeat percutaneous coronary intervention and bypass
      surgery. Although follow-up costs were reduced by 2571 dollars per patient with
      SESs, aggregate 1-year costs remained 309 dollars per patient higher. The
      incremental cost-effectiveness ratio for SES was 1650 dollars per repeat
      revascularization event avoided or 27,540 dollars per quality-adjusted year of
      life gained, values that compare reasonably with other accepted medical
      interventions. Under updated treatment assumptions regarding available stent
      lengths and duration of antiplatelet therapy, use of SESs was projected to reduce
      total 1-year costs compared with BMSs. CONCLUSIONS: Although use of SESs was not
      cost-saving compared with BMS implantation, for patients undergoing percutaneous
      coronary intervention of complex coronary stenoses, their use appears to be
      reasonably cost-effective within the context of the US healthcare system.

PMID- 15262845
TI  - Sirolimus in de novo heart transplant recipients reduces acute rejection and
      prevents coronary artery disease at 2 years: a randomized clinical trial.
AB  - BACKGROUND: Sirolimus reduces acute rejection in renal transplant recipients and
      prevents vasculopathy in nonhuman primates and in-stent restenosis in humans. Its
      effects on rejection and transplant vasculopathy in human heart transplant
      recipients are unknown. METHODS AND RESULTS: In a randomized, open-label study,
      sirolimus was compared with azathioprine in combination with cyclosporine and
      steroids administered from the time of cardiac transplantation. We report 6-month
      rejection rates (primary end point), 12-month safety and efficacy data, and 6-
      and 24-month graft vasculopathy data in 136 cardiac allograft recipients randomly
      assigned (2:1) to sirolimus (n=92) or azathioprine (n=44). At 6 months, the
      proportion of patients with grade 3a or greater acute rejection was 32.4% for
      sirolimus 3 mg/d (P=0.027), 32.8% for sirolimus 5 mg/d (P=0.013), and 56.8% for
      azathioprine. Patient survival at 12 months was comparable among groups.
      Intracoronary ultrasound at 6 weeks, 6 months, and 2 years demonstrated highly
      significant progression of transplant vasculopathy in azathioprine-treated
      patients. At 6 months, a highly significant absence of progression in intimal
      plus medial proliferation and significant protection against luminal encroachment
      was evident in sirolimus-treated patients, and these effects were sustained at 2
      years. CONCLUSIONS: Sirolimus use from the time of transplantation approximately
      halved the number of patients experiencing acute rejection. The measurable
      development of transplant vasculopathy at 6 months and 2 years in patients
      receiving azathioprine was not observed in patients receiving sirolimus.

PMID- 15262846
TI  - Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial
      dysfunction in humans.
AB  - BACKGROUND: 20-hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 (omega
      hydroxylase) metabolite of arachidonic acid with vasoconstrictor activity that
      may be involved in the pathogenesis of hypertension. In humans, there are few
      data relating 20-HETE to vascular pathophysiology. This study aimed to determine
      whether urinary 20-HETE excretion is related to blood pressure or vascular
      endothelial function in humans. METHODS AND RESULTS: Sixty-six subjects (37
      males, 29 females), including 29 with untreated hypertension, had urinary 20-HETE
      excretion measured by gas chromatography/mass spectrometry. There was no
      significant difference for 20-HETE excretion between hypertensive and
      normotensive subjects. 20-HETE excretion was positively related to body mass
      index and sodium excretion. There was a significant inverse association between
      urinary 20-HETE and endothelium-dependent vasodilation measured by flow-mediated
      dilation of the brachial artery (P=0.006). There was no association with
      vasodilator responses to nitroglycerin. In multiple regression analysis, 20-HETE
      remained an independent predictor of endothelium-dependent vasodilation after
      adjustment for age, body mass index, and blood pressure. When gender was included
      in the model, the relationship between 20-HETE and flow-mediated dilation was
      attenuated. Separate analysis by gender revealed that in women, hypertensive
      subjects had significantly higher 20-HETE excretion than normotensive subjects,
      but this was not seen in men. In women, 20-HETE was positively related to
      diastolic and systolic blood pressure. In men, 20-HETE was positively related to
      body mass index. CONCLUSIONS: This is the first demonstration of an association
      between 20-HETE excretion and in vivo vascular function in humans. Given the
      negative modulatory role of nitric oxide on omega-hydroxylase, the present
      results suggest a potentially important role for 20-HETE in human vascular
      physiology.

PMID- 15262847
TI  - Systemic lupus erythematosus: an independent risk factor for endothelial
      dysfunction in women.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) patients have a significantly
      increased risk of coronary heart disease (CHD) that is not fully explained by
      classic risk factors. Endothelial dysfunction is an early stage in the process of
      atherogenesis. Our aim was to determine whether endothelial dysfunction occurs in
      SLE and whether it is associated with the occurrence of classic Framingham risk
      factors. METHODS AND RESULTS: We studied 62 women with SLE (1997 revised
      criteria) and 38 healthy women. Demographic and risk factor data were collected.
      In patients, disease activity and treatment-related parameters were also
      assessed. Endothelial function was assessed by flow-mediated dilation (FMD) in
      the brachial artery in response to reactive hyperemia. Carotid intima-media
      thickness (IMT) and the presence of carotid plaques were also assessed in SLE
      patients. FMD was impaired in SLE patients (median, 3.6%; range, -6.3% to 13.7%;
      versus median, 6.9%; range, -6.6% to 17.8%, P<0.01). Using multiple regression
      analysis that included all subjects in which we retained all the classic CHD risk
      factors, we found that systolic blood pressure (P=0.019) and SLE (P=0.017) were
      significantly associated with impaired FMD. Within SLE patients, IMT showed a
      negative correlation with percent FMD (r=-0.37, P<0.01). In stepwise multiple
      regression of SLE patients only that also included SLE factors and IMT, IMT alone
      was independently associated with FMD (P=0.037). CONCLUSIONS: Patients with SLE
      have endothelial dysfunction that remained significant even after adjustment for
      other classic CHD risk factors. Within SLE patients, endothelial dysfunction
      correlates negatively with IMT, another marker of early atherosclerosis.
      Understanding the mechanism(s) of endothelial dysfunction in SLE may suggest
      novel strategies for CHD prevention in this context.

PMID- 15262848
TI  - Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat
      ventricular myocytes via a Rac1-dependent mechanism.
AB  - BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) inhibit
      myocyte hypertrophy in vitro and ameliorate the progression of cardiac remodeling
      in vivo, possibly because of inhibition of the small GTPase Rac1. The role of
      Rac1 in mediating myocyte apoptosis is not known. beta-Adrenergic receptor
      (betaAR)-stimulated myocyte apoptosis is mediated via activation of c-Jun NH2
      terminal kinase (JNK), leading to activation of the mitochondrial death pathway.
      We hypothesized that betaAR-stimulated apoptosis in adult rat ventricular myocyte
      (ARVMs) is mediated by Rac1 and inhibited by statins. METHODS AND RESULTS: betaAR
      stimulation increased apoptosis, as assessed by transferase-mediated nick-end
      labeling, from 5+/-1% to 24+/-2%. betaAR stimulation also increased Rac1
      activity. Adenoviral overexpression of a dominant-negative mutant of Rac1
      inhibited betaAR-stimulated apoptosis, JNK activation, cytochrome C release, and
      caspase-3 activation. Cerivastatin likewise inhibited the betaAR-stimulated
      activation of Rac1, decreased betaAR-stimulated apoptosis to 11+/-2%, and
      inhibited JNK activation, cytochrome C release, and caspase-3 activation.
      CONCLUSIONS: betaAR stimulation causes Rac1 activation, which is required for
      myocyte apoptosis and leads to activation of JNK and the mitochondrial death
      pathway. Cerivastatin inhibits betaAR-stimulated activation of Rac1 and thereby
      inhibits JNK-dependent activation of the mitochondrial death pathway and
      apoptosis. The beneficial effects of statins on the myocardium may be mediated in
      part via inhibition of Rac1-dependent myocyte apoptosis.

PMID- 15262849
TI  - Adrenomedullin administration immediately after myocardial infarction ameliorates
      progression of heart failure in rats.
AB  - BACKGROUND: Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM
      levels increase in patients with acute myocardial infarction (MI). This study was
      performed to determine whether AM administration immediately after acute MI
      inhibits progression of heart failure in rats. METHODS AND RESULTS: Rats were
      infused with 1.0 microg/h IP AM or saline over 7 days immediately after MI
      inducted by left coronary ligation and were examined 9 weeks after MI. Compared
      with the saline infusion, AM infusion significantly improved survival (59% versus
      81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (-28%;
      P<0.01), lung weight (-26%; P<0.01), left ventricular (LV) end-diastolic pressure
      (11.4+/-2.0 versus 4.0+/-0.6 mm Hg, mean+/- SEM; P<0.01), collagen volume
      fraction of noninfarcted LV (-39%; P<0.05), and plasma levels of endogenous rat
      AM (-38%; P<0.05) without affecting infarct size. To investigate the mechanism of
      AM actions, another series of MI rats infused with AM were killed on day 7. AM
      infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI
      but significantly reduced urinary excretion of isoprostane (-61%; P<0.01) and
      noninfarcted LV mRNA levels of ACE (-31%; P<0.05) and p22-phox (-30%; P<0.05).
      CONCLUSIONS: AM administration during the early period of MI improved the
      survival and ameliorated progression of LV remodeling and heart failure. This
      beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA
      expression in noninfarcted LV in the AM infusion period.

PMID- 15262850
TI  - AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth
      muscle cell proliferation.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK) is a stress-activated protein
      kinase that works as a metabolic sensor of cellular ATP levels. Here, we
      investigated whether AMPK signaling has a role in the regulation of the
      angiotensin II (Ang II)-induced proliferation signal in rat vascular smooth
      muscle cells (VSMCs). METHODS AND RESULTS: Aminoimidazole-4-carboxamide-1-beta
      ribofuranoside (AICAR) activated AMPK in rat VSMCs and inhibited Ang II-induced
      extracellular signal-regulated kinase 1/2 phosphorylation but not that of p38
      MAPK or Akt/PKB. Although Ang II activated AMPK, this activation was
      significantly inhibited by catalase, N-acetylcysteine, and diphenyleneiodonium
      chloride, an NADPH oxidase inhibitor. Moreover, the observation that AMPK was
      activated by H2O2 suggests that AMPK is redox sensitive. The Ang II type 1
      receptor antagonist valsartan but not the Ang II type 2 receptor antagonist
      PD123319 significantly inhibited Ang II-induced AMPK activation, suggesting that
      Ang II-induced AMPK activation was Ang II type 1 receptor dependent. Whereas 3H
      thymidine incorporation by VSMCs treated with Ang II was significantly inhibited
      when the cells were pretreated with 1 mmol/L AICAR, the inhibition of AMPK by
      dominant-negative AMPK overexpression augmented Ang II-induced cell
      proliferation. Subcutaneous injection of AICAR (1 mg/g body weight per day) for 2
      weeks suppressed neointimal formation after transluminal mechanical injury of the
      rat femoral artery. CONCLUSIONS: Our findings indicate that Ang II-induced AMPK
      activation is synchronized with extracellular signal-regulated kinase signaling
      and that AMPK works as an inhibitor of the Ang II proliferative pathway. AMPK
      signaling might serve as a new therapeutic target of vascular remodeling in
      cardiovascular diseases.

PMID- 15262851
TI  - Relationship between arterial stiffness and subclinical aortic atherosclerosis.
AB  - BACKGROUND: Noninvasive measures of arterial compliance may be useful for the
      detection of subclinical atherosclerosis. METHODS AND RESULTS: Measures of calf
      and thigh arterial compliance (MaxV50) were recorded in 267 subjects who also
      underwent MRI of the distal aorta to quantify distal aorta atherosclerosis. The
      average of calf and thigh MaxV50 was strongly predictive of extent of aortic
      atherosclerosis and risk of being in the top quartile of aortic atherosclerosis
      after adjustment for the Framingham Coronary Risk Score (FCRS) or the combination
      of the FCRS and C-reactive protein (P<0.0001). The areas under the receiver
      operating curves predicting the top quartile of gender-specific aortic
      atherosclerosis were 0.57, 0.60, and 0.75 for models containing the FCRS, the
      FCRS and C-reactive protein, and the FCRS, C-reactive protein, and the average of
      calf and thigh MaxV50. CONCLUSIONS: Lower-extremity arterial compliance may
      identify subjects with extensive subclinical atherosclerosis. Further studies
      examining the potential value of arterial stiffness as a screening tool to guide
      initiation of more aggressive preventive interventions are warranted.

PMID- 15262852
TI  - Gene therapy in congestive heart failure.

PMID- 15262853
TI  - Vulnerable plaque: the devil is in the details.

PMID- 15262854
TI  - Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation).

PMID- 15262855
TI  - Images in cardiovascular medicine. Infiltrative eosinophilic myocarditis
      diagnosed and localized by cardiac magnetic resonance imaging.

PMID- 15262856
TI  - Histology of sudden death in arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.

PMID- 15262857
TI  - Sex hormones and asymmetric dimethylarginine in transplant arteriosclerosis.

PMID- 15262859
TI  - Endothelial function in a large community.

PMID- 15262858
TI  - In percutaneous transluminal septal myocardial ablation for hypertrophic
      obstructive cardiomyopathy, it is not the speed of intracoronary alcohol
      injection but the amount of alcohol injected that determines the resultant
      infarct size.

PMID- 15262860
TI  - Troponin T release in hemodialysis patients.

PMID- 15262862
TI  - Who benefits from the embargo?

PMID- 15262861
TI  - Prostitution laws: health risks and hypocrisy.

PMID- 15262863
TI  - Who benefits from the embargo?

PMID- 15262864
TI  - Who benefits from the embargo?

PMID- 15262866
TI  - Dyslipidemia guidelines.

PMID- 15262868
TI  - Dyslipidemia guidelines.

PMID- 15262871
TI  - Canada signs agreements to potentially share drug information with the US and
      Australia.

PMID- 15262872
TI  - Medicare on trial: Chaoulli and autism case.

PMID- 15262873
TI  - Cochrane Collaboration's stand versus industry funding.

PMID- 15262874
TI  - Quebec strikes committee on Clostridium difficile.

PMID- 15262876
TI  - Stats Can: 14% of Canadians have no family doctor.

PMID- 15262877
TI  - Canada advances Russia's attitude toward AIDS.

PMID- 15262878
TI  - Enhanced surveillance for Salmonella Newport.

PMID- 15262879
TI  - Rosuvastatin (Crestor) and rhabdomyolysis.

PMID- 15262880
TI  - A neonate with denuded skin: Hay-Wells syndrome.

PMID- 15262881
TI  - Decrease in antibiotic use among children in the 1990s: not all antibiotics, not
      all children.
AB  - BACKGROUND: Decreases in antibiotic use were widely reported in the 1990s. This
      study was undertaken to determine trends in the use of antibiotics from fiscal
      year (FY) 1995 (April 1995 to March 1996) to FY 2001 in a complete population of
      Manitoba children. METHODS: Using Manitoba's health care databases, we determined
      annual population-based rates of antibiotic prescription among children by
      antibiotic class (narrow-spectrum and broader-spectrum antibiotics), age group,
      physician diagnosis (e.g., otitis media or bronchitis) and neighbourhood income
      in urban areas (derived from the 1996 census). Antibiotic prescription rates were
      generated within a generalized linear model framework with general estimating
      equations, and differences between FY 2001 and FY 1995 were tested. Differences
      in antibiotic use over time were compared across antibiotic classes, age groups,
      diagnoses and income neighbourhoods. RESULTS: The overall antibiotic prescription
      rate decreased by almost one-third, from 1.2 prescriptions per child in FY 1995
      to 0.9 prescriptions in FY 2001. Total antibiotic use declined for all
      respiratory tract infections; decreases were greatest for the sulfonamides
      (decrease to less than one-third the FY 1995 rate) and narrow-spectrum macrolides
      (decrease to less than half the FY 1995 rate). In contrast, the FY 2001 rate for
      broader-spectrum macrolides was as much as 12.5 times the FY 1995 rate. Otitis
      media accounted for one-quarter of the use of the latter agents. Preschool
      children and low-income children received the greatest number of antibiotic
      prescriptions. Declines in antibiotic prescriptions were of a lesser magnitude
      for low-income children (for whom rates in FY 2001 were four-fifths the rates in
      FY 1995) than for higher-income children (for whom rates in FY 2001 were about
      two-thirds the rates in FY 1995). INTERPRETATION: Overall, antibiotic use
      declined over the late 1990s in this population of Canadian children, but the
      increasing use of broader-spectrum macrolides and higher rates of antibiotic use
      among preschool and low-income children may have implications for antibiotic
      resistance.

PMID- 15262882
TI  - Evidence-based prescribing of antibiotics for children: role of socioeconomic
      status and physician characteristics.
AB  - BACKGROUND: Evidence-based guidelines for antibiotic use are well established,
      but nonadherence to these guidelines continues. This study was undertaken to
      determine child, household and physician factors predictive of nonadherence to
      evidence-based antibiotic prescribing in children. METHODS: The prescription and
      health care records of 20 000 Manitoba children were assessed for 2 criteria of
      nonadherence to evidence-based antibiotic prescribing during the period from
      fiscal year 1996 (April 1996 to March 1997) to fiscal year 2000: receipt of an
      antibiotic for a viral respiratory tract infection (VRTI) and initial use of a
      second-line agent for acute otitis media, pharyngitis, pneumonia, urinary tract
      infection or cellulitis. The likelihood of nonadherence to evidence-based
      prescribing, according to child demographic characteristics, physician factors
      (specialty and place of training) and household income, was determined from
      hierarchical linear modelling. Child visits were nested within physicians, and
      the most parsimonious model was selected at p < 0.05. RESULTS: During the study
      period, 45% of physician visits for VRTI resulted in an antibiotic prescription,
      and 20% of antibiotic prescriptions were for second-line antibiotics. Relative to
      general practitioners, the odds ratio for antibiotic prescription for a VRTI was
      0.51 (95% confidence interval [CI] 0.42-0.62) for pediatricians and 1.58 (95% CI
      1.03-2.42) for other specialists. The likelihood that an antibiotic would be
      prescribed for a VRTI was 0.99 for each successive 10,000 Canadian dollars
      increase in household income. Pediatricians and other specialists were more
      likely than general practitioners to prescribe second-line antibiotics for
      initial therapy. Both criteria for nonadherence to evidence-based prescribing
      were 40% less likely among physicians trained in Canada or the United States than
      among physicians trained elsewhere. INTERPRETATION: The links that we identified
      between nonadherence to evidence-based antibiotic prescribing in children and
      physician specialty and location of training suggest opportunities for
      intervention. The independent effect of household income indicates that parents
      also have an important role.

PMID- 15262883
TI  - Reconvening the federal committee on prostitution law reform.

PMID- 15262884
TI  - CME and the pharmaceutical industry: two worlds, three views, four steps.

PMID- 15262885
TI  - The future sponsorship of CME in Canada: industry, government, physicians or a
      blend?

PMID- 15262886
TI  - Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the
      status of treatment.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary
      fibrotic lung disease. The diagnostic histological changes are called usual
      interstitial pneumonia and are characterized by histological temporal
      heterogeneity, whereby normal lung tissue is interspersed with interstitial
      fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show
      restricted volumes and capacities, preserved flows and evidence of decreased gas
      exchange. High-resolution computed axial tomography demonstrates evidence of
      fibrosis and lung remodelling such as honeycomb cysts and traction
      bronchiectasis. There is no known effective treatment for IPF, but lung
      transplantation improves survival.

PMID- 15262887
TI  - Move it or lose it: axis specification in Xenopus.
AB  - A long-standing question in developmental biology is how amphibians establish a
      dorsoventral axis. The prevailing view has been that cortical rotation is used to
      move a dorsalizing activity from the bottom of the egg towards the future dorsal
      side. We review recent evidence that kinesin-dependent movement of particles
      containing components of the Wnt intracellular pathway contributes to the
      formation of the dorsal organizer, and suggest that cortical rotation functions
      to align and orient microtubules, thereby establishing the direction of particle
      transport. We propose a new model in which active particle transport and cortical
      rotation cooperate to generate a robust movement of dorsal determinants towards
      the future dorsal side of the embryo.

PMID- 15262888
TI  - Beta-catenin signaling is required for neural differentiation of embryonic stem
      cells.
AB  - Culture of embryonic stem (ES) cells at high density inhibits both beta-catenin
      signaling and neural differentiation. ES cell density does not influence beta
      catenin expression, but a greater proportion of beta-catenin is targeted for
      degradation in high-density cultures. Moreover, in high-density cultures, beta
      catenin is preferentially localized to the membrane further reducing beta-catenin
      signaling. Increasing beta-catenin signaling by treatment with Wnt3a-conditioned
      medium, by overexpression of beta-catenin, or by overexpression of a dominant
      negative form of E-cadherin promotes neurogenesis. Furthermore, beta-catenin
      signaling is sufficient to induce neurogenesis in high-density cultures even in
      the absence of retinoic acid (RA), although RA potentiates the effects of beta
      catenin. By contrast, RA does not induce neurogenesis in high-density cultures in
      the absence of beta-catenin signaling. Truncation of the armadillo domain of beta
      catenin, but not the C terminus or the N terminus, eliminates its proneural
      effects. The proneural effects of beta-catenin reflect enhanced lineage
      commitment rather than proliferation of neural progenitor cells. Neurons induced
      by beta-catenin overexpression either alone or in association with RA express the
      caudal neuronal marker Hoxc4. However, RA treatment inhibits the beta-catenin
      mediated generation of tyrosine hydroxylase-positive neurons, suggesting that not
      all of the effects of RA are dependent upon beta-catenin signaling. These
      observations suggest that beta-catenin signaling promotes neural lineage
      commitment by ES cells, and that beta-catenin signaling may be a necessary co
      factor for RA-mediated neuronal differentiation. Further, enhancement of beta
      catenin signaling with RA treatment significantly increases the numbers of
      neurons generated from ES cells, thus suggesting a method for obtaining large
      numbers of neural species for possible use in for ES cell transplantation.

PMID- 15262889
TI  - Combinatorial Fgf and Bmp signalling patterns the gastrula ectoderm into
      prospective neural and epidermal domains.
AB  - Studies in fish and amphibia have shown that graded Bmp signalling activity
      regulates dorsal-to-ventral (DV) patterning of the gastrula embryo. In the
      ectoderm, it is thought that high levels of Bmp activity promote epidermal
      development ventrally, whereas secreted Bmp antagonists emanating from the
      organiser induce neural tissue dorsally. However, in zebrafish embryos, the
      domain of cells destined to contribute to the spinal cord extends all the way to
      the ventral side of the gastrula, a long way from the organiser. We show that in
      vegetal (trunk and tail) regions of the zebrafish gastrula, neural specification
      is initiated at all DV positions of the ectoderm in a manner that is unaffected
      by levels of Bmp activity and independent of organiser-derived signals. Instead,
      we find that Fgf activity is required to induce vegetal prospective neural
      markers and can do so without suppressing Bmp activity. We further show that Bmp
      signalling does occur within the vegetal prospective neural domain and that Bmp
      activity promotes the adoption of caudal fate by this tissue.

PMID- 15262890
TI  - Founder myoblasts and fibre number during adult myogenesis in Drosophila.
AB  - We have examined the mechanisms underlying the setting of myotubes and choice of
      myotube number in adult Drosophila. We find that the pattern of adult myotubes is
      prefigured by a pattern of duf-lacZ-expressing myoblasts at appropriate
      locations. Selective expression of duf-lacZ in single myoblasts emerges from
      generalized, low-level expression in all adult myoblasts during the third larval
      instar. The number of founders, thus chosen, corresponds to the number of fibres
      in a muscle. In contrast to the embryo, the selection of individual adult founder
      cells during myogenesis does not depend on Notch-mediated lateral inhibition. Our
      results suggest a general mechanism by which multi-fibre muscles can be
      patterned.

PMID- 15262891
TI  - Investigation of the infertile couple: when is the appropriate time to explore
      female infertility?
AB  - While the appropriate method for the investigation of female infertility
      continues to be debated, the timing of the investigation has received less
      attention. The current approach is time-consuming, and paradoxically may lead to
      overtreatment as well as undertreatment. Recent findings on fecundity and the
      conception window in humans have important implications for the timing of the
      investigation of female infertility. The findings support the view that fertility
      oriented intercourse may have a major impact in reducing the time to pregnancy.
      Procedures for the investigation of female infertility are becoming less invasive
      and more accurate, while the therapies for infertility are more effective. It is
      proposed that under appropriate circumstances female infertility should be
      investigated after 6 months of fertility-oriented intercourse.

PMID- 15262892
TI  - Ovarian cryopreservation versus ovarian suppression by GnRH analogues: primum non
      nocere.

PMID- 15262893
TI  - Developmental potential of human pronuclear zygotes in relation to their
      pronuclear orientation.

PMID- 15262895
TI  - No decrease occurs in the number of COCs retrieved with repeated IVF cycles.

PMID- 15262896
TI  - Arterial embolization for postpartum haemorrhage: let's stay cautious.

PMID- 15262897
TI  - CD4+ T cells are important for clearance of DA strain of TMEV from the central
      nervous system of SJL/J mice.
AB  - DA and other TO subgroup strains of Theiler's murine encephalomyelitis virus
      synthesize a protein called L* which interferes with DA virus clearance from the
      central nervous system of susceptible SJL mice, thereby fostering virus
      persistence and a late demyelinating disease. By using CD4 (-/-) and CD8 (-/-)
      mice as well as adoptive transfer studies we demonstrate that susceptible mouse
      strains are capable of clearing DA virus through a CD4+ T cell-dependent activity
      that is inhibited by L*.

PMID- 15262898
TI  - Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L
      selectinlow tumor-sensitized lymphocytes.
AB  - We have shown that tumor vaccine-sensitized draining lymph node (vDLN) cells
      activated ex vivo with bryostatin and ionomycin (B/I) were capable of inducing
      antigen-specific regression of a murine mammary tumor, 4T07. vDLN cells not
      activated with B/I were ineffective. We hypothesized that B/I selectively
      activates tumor-sensitized (CD62Llow) lymphocytes, to account for the highly
      potent and tumor-specific activity. We hypothesized that CD8+ CD62Llow cells may
      be preferentially activated by B/I treatment, infiltrate the tumors and mediate
      tumor regression in mice. 4T07-IL2 tumor cells were injected into one hind
      footpad of BALB/c mice. Ten days later, vDLN were harvested and separated based
      on CD62L expression. After separation, cells were activated with B/I, expanded
      with IL2 (40 IU/ml) for 10 days, and adoptively transferred to 4T07 tumor bearing
      mice. Naive mice were also treated with different subsets of T cells and later
      were challenged with 4T07 tumor cells. To test in vitro responses to antigen,
      expanded lymphocytes were cultured either alone or with irradiated 4T07 tumor
      cells. Supernatants were harvested after 24 h and tested by ELISA for IFN-gamma.
      The importance of the host immune response was tested by AIT into 4T07-bearing
      nude athymic mice. Host mice were depleted in vivo of CD4 or CD8 T cells after
      vDLN AIT to ascertain the mediators of tumor regression. In order to track B/I
      activated vDLN cells, they were prestained with CFSE prior to adoptive transfer
      into tumor-bearing hosts. At various time points, tumors, spleens and lymph nodes
      of host mice were harvested, dual stained for activation marker expression and
      analyzed by flow cytometry. CD62Llow cells expanded 12-fold more than CD62Lhigh
      lymphocytes during the 10 day culture period. Supernatant from CD62Llow cells +
      4T07 cultures contained 33-fold more IFN-gamma than supernatant from CD62Lhigh
      cells + 4T07 cultures (843.9 pg/ml +/- 135.8 vs 25.89 pg/ml +/- 0.01). Adoptive
      transfer of CD62Llow lymphocytes induced complete tumor regressions in all mice,
      while tumors regressed in only 17% of mice treated with CD62Lhigh lymphocytes.
      Naive mice that received B/I-activated CD62Llow cells were protected from future
      tumor challenges, while mice given CD62Lhigh cells did not exhibit the same
      resistance to tumor growth. Tumors in nude host mice regressed after AIT
      treatment. In vivo depletion of CD4 T cells after AIT did not inhibit tumor
      regression, but CD8 T cell depletion abrogated tumor regression. vDLN cells
      tracked preferentially to tumor draining lymph nodes and proliferated in vivo,
      persisting for at least 21 days, and were 95% CD44+ and 39% CD69+. Bryostatin 1
      and ionomycin, by increasing PKC activity and intracellular calcium,
      respectively, mimic intracellular signals that result in T cell activation.
      CD62Llow cells are preferentially activated by B/I, leading to a highly effective
      anti-tumor T cell population.

PMID- 15262899
TI  - Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading
      autoimmune responses to proliferating cell nuclear antigen multiprotein complexes
      in lupus patients.
AB  - Using 2-dimensional electrophoresis and ion-pair chromatography, we have
      identified elements of proliferating cell nuclear antigen (PCNA) multiprotein
      complexes that are reactive to antibodies in sera from patients with systemic
      lupus erythematosus. Among the various elements of the complexes, a 37 kDa
      protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from
      patients with other connective tissue diseases, was identified as glyceraldehyde
      3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera
      reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti
      GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both
      nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2
      cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the
      presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal
      analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune
      response to spread from GAPDH to other elements of PCNA complexes, and the
      presence of anti-GAPDH antibodies was significantly correlated with increased
      levels of serum PCNA. Taken together, these findings suggest that GAPDH
      interacting with PCNA in association with its cellular function is a novel
      autoantigen recognized by lupus sera, and that GAPDH thus plays an important role
      in the induction of autoimmune responses against the PCNA complex.

PMID- 15262900
TI  - TCR-mediated activation promotes GITR upregulation in T cells and resistance to
      glucocorticoid-induced death.
AB  - T lymphocytes (pivotal in many inflammatory pathologies) are targets for
      glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via
      glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We
      delineated here the expression of a recently identified glucocorticoid-induced
      TNF receptor (GITR) induced by GC and by TCR-mediated T-cell activation in GC
      receptor (GR)-deficient mice (GR-/-). We also compared the action of GC on GITR+
      and GITR- T cells by monitoring apoptosis, proliferation and cytokine production
      stimulated by anti-CD3 antibody. By using GR-/- mice, we observed that the
      development of GITR+ T cells (both in thymus and periphery) is not dependent upon
      GR signaling. This contradicts the implication of GITR's name reflecting GC
      induction. TCR-mediated T-cell activation induced GITR expression in both GR+/+
      and GR-/- cells. Somewhat unexpectedly, there was very modest GITR upregulation
      on GR+/+ T cells by a range of GC doses (10(-8) to 10(-6) M). Constitutive
      expression of GITR by a subset of CD4+ cells did not significantly render them
      resistant to GC-induced cell death. However, TCR-induced GITR upregulation on
      GR+/+ T cells was correlated with resistance to GC-mediated apoptosis suggesting
      that GITR, in conjunction with other (as yet unidentified) TCR-induced factors,
      protects T cells from apoptosis. Thus, even though GC is a potent inducer of
      apoptosis of T cells, activated T cells are resistant to GC-mediated killing.
      Meanwhile, although GC suppressed anti-CD3-induced cytokine production, cell
      proliferation was unaffected by GC in GR+/+ mice. GR deficiency has no effect on
      anti-CD3-induced cytokine production and proliferation. Our findings also have
      implications for GC treatment in that it would be more difficult to abrogate an
      ongoing T-cell mediated inflammatory response than to prevent its induction.

PMID- 15262901
TI  - Nitric oxide and the regulation of large artery stiffness: from physiology to
      pharmacology.

PMID- 15262902
TI  - Is the extrapolated adult dose of fosinopril safe and effective in treating
      hypertensive children?
AB  - We evaluated the efficacy, safety, and dose-response relationship of fosinopril
      in children aged 6 to 16 years with hypertension or high-normal blood pressure
      with an associated medical condition requiring treatment. The study was a
      prospective, double-blind, placebo-controlled trial conducted in 78 clinical
      sites in the United States, Russia, and Israel. There were 4 phases: a screening
      phase of 10 days maximum, a 4-week dose-response phase, a placebo withdrawal
      phase of 2 weeks maximum, and a 52-week open-label safety phase. The primary
      objective of the dose-response phase was to determine whether low (0.1 mg/kg),
      medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established
      adult dosing affect trough seated systolic blood pressure. During the dose
      response phase, all 3 doses were equally effective in lowering systolic blood
      pressure. During the placebo withdrawal phase, there was an adjusted mean
      systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg
      for the fosinopril group, a net withdrawal effect of 3.7 mm Hg (P=0.013).
      Fosinopril was well tolerated; serious adverse events occurred infrequently and
      were generally not attributed to fosinopril. Because children appear to be more
      sensitive to lower doses of fosinopril than adults, starting doses for children
      should be < or =0.1 mg/kg.

PMID- 15262903
TI  - Reactive oxygen species, vascular oxidative stress, and redox signaling in
      hypertension: what is the clinical significance?
AB  - Metabolism of oxygen by cells generates potentially deleterious reactive oxygen
      species (ROS). Under normal conditions the rate and magnitude of oxidant
      formation is balanced by the rate of oxidant elimination. However, an imbalance
      between prooxidants and antioxidants results in oxidative stress, which is the
      pathogenic outcome of oxidant overproduction that overwhelms the cellular
      antioxidant capacity. The kidney and vasculature are rich sources of NADPH
      oxidase-derived ROS, which under pathological conditions play an important role
      in renal dysfunction and vascular damage. Strong experimental evidence indicates
      that increased oxidative stress and associated oxidative damage are mediators of
      renovascular injury in cardiovascular pathologies. Increased production of
      superoxide anion and hydrogen peroxide, reduced nitric oxide synthesis, and
      decreased bioavailability of antioxidants have been demonstrated in experimental
      and human hypertension. These findings have evoked considerable interest because
      of the possibilities that therapies targeted against free radicals by decreasing
      ROS generation or by increasing nitric oxide availability and antioxidants may be
      useful in minimizing vascular injury and renal dysfunction and thereby prevent or
      regress hypertensive end-organ damage. This article highlights current
      developments in the field of ROS and hypertension, focusing specifically on the
      role of oxidative stress in hypertension-associated vascular damage. In addition,
      recent clinical trials investigating cardiovascular benefits of antioxidants are
      discussed, and some explanations for the rather disappointing results from these
      studies are addressed. Finally, important avenues for future research in the
      field of ROS, oxidative stress, and redox signaling in hypertension are
      considered.

PMID- 15262904
TI  - Reduction of vascular noradrenaline sensitivity by AT1 antagonists depends on
      functional sympathetic innervation.
AB  - Blockade of angiotensin II type-1 (AT1) receptors has been shown to reduce the
      magnitude of the blood pressure response to noradrenaline in pithed rats via an
      unidentified mechanism. Dose-response curves were established for the
      noradrenaline-induced (10(-12) to 10(-7) mol/kg) increase of diastolic blood
      pressure in pithed rats treated with tubocurarine, propranolol, and atropine.
      Candesartan (1 mg/kg) increased the ED50 of the noradrenaline response (1.3+/-0.1
      nmol/kg) up to 20-fold. Vasopressor responsiveness to noradrenaline was
      attenuated specifically, whereas the vasopressin-induced increase in diastolic
      blood pressure was maintained. Specific involvement of AT1 receptors was
      confirmed by equivalent actions of losartan. Blockade of norepinephrine
      transporter or alpha2-adrenoceptors using desipramine or rauwolscine reduced the
      losartan-induced shifts in the ED50 values of noradrenaline by 63% and 21%,
      respectively. Combined blockade of norepinephrine transporter and alpha2
      adrenoceptors eliminated the influence of losartan on noradrenaline sensitivity
      (ED50 5.5+/-1.3 versus 5.6+/-1.2 nmol/kg), a result also observed after
      sympathetic denervation by reserpine (ED50 7.1+/-0.8 versus 7.8+/-0.8 nmol/kg).
      Our experiments show that the reduction of vascular noradrenaline sensitivity by
      AT1 blockade is dependent on the intact functioning of both neuronal
      noradrenaline uptake via norepinephrine transporter and presynaptic alpha2
      mediated autoinhibition, exclusively provided by the sympathetic innervation.
      These newly identified mechanisms may contribute to the antihypertensive and
      protective actions of AT1 blockers.

PMID- 15262906
TI  - Is vascular endothelial growth factor a missing link between hypertension and
      inflammation?

PMID- 15262905
TI  - Essential role of vascular endothelial growth factor in angiotensin II-induced
      vascular inflammation and remodeling.
AB  - Angiotensin II (Ang II) upregulates vascular endothelial growth factor (VEGF) and
      activates vascular inflammation. However, the decisive role of VEGF in Ang II
      induced vascular inflammation and remodeling has not been addressed. Ang II
      infusion to wild-type mice increased local expression of VEGF and its receptors
      in cells of aortic wall and plasma VEGF, and caused aortic inflammation (monocyte
      infiltration) and remodeling (wall thickening and fibrosis). Hypoxia-inducible
      factor-1alpha colocalized with VEGF-positive cell types. Blockade of VEGF by the
      soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated the Ang II-induced
      inflammation and remodeling. The sFlt-1 gene transfer also inhibited the
      increased expression of VEGF and inflammatory factors such as monocyte
      chemoattractant protein-1. In contrast, sFlt-1 gene transfer did not affect Ang
      II-induced arterial hypertension and cardiac hypertrophy. VEGF is an essential
      mediator in Ang II-induced vascular inflammation and structural changes through
      its proinflammatory actions.

PMID- 15262907
TI  - Effects of local administrations of tempol and diethyldithio-carbamic on
      peripheral nerve activity.
AB  - We have recently shown that systemic administration of a superoxide dismutase
      mimetic, tempol, resulted in decreases in mean arterial pressure and heart rate
      along with a reduction in renal sympathetic nerve activity (RSNA). It has also
      been shown that these parameters are significantly increased by systemic
      administration of a superoxide dismutase inhibitor, diethyldithio-carbamic
      (DETC), indicating a potential role of reactive oxygen species in the regulation
      of RSNA. In this study, we examined the effects of local administrations of 4
      hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) and DETC on RSNA in
      anesthetized rats. Either tempol or DETC was directly administered onto the renal
      sympathetic nerves located between the electrode and ganglion. Local application
      of tempol (10 microL, 0.17 to 1.7 mol/L, n=6) resulted in dose-dependent
      decreases in integrated RSNA (by -81+/-6% at 1.7 mol/L) without alterations in
      mean arterial pressure and heart rate. In contrast, DETC (10 microL, 0.17 to 1.7
      mol/L, n=6) increased RSNA dose-dependently. The responses of RSNA to tempol and
      DETC were significantly greater in spontaneously hypertensive rats than in
      normotensive rats (n=6, respectively). Local application of sodium nitroprusside
      (1 mmol/L) or N(G)-nitro-L-arginine methyl ester (0.11 mol/L) altered neither
      basal RSNA nor tempol-induced reductions in RSNA (n=6 and 5, respectively). A
      voltage-gated potassium channel blocker, 4-aminopyridine (0.1 mol/L),
      significantly decreased basal RSNA (by -81+/-1%) and completely prevented DETC
      induced increases in RSNA (n=5). These results suggest that reactive oxygen
      species play a role in the regulation of peripheral sympathetic nerve activity,
      and that at least part of this mechanism is mediated through voltage-gated
      potassium channels.

PMID- 15262909
TI  - Transcriptional regulation of type B human natriuretic Peptide receptor gene
      promoter: dependence on Sp1.
AB  - The type B natriuretic peptide receptor (NPR-B) is the cognate receptor for the C
      type natriuretic peptide and, as such, is responsible for signaling growth
      suppressant activity in vascular smooth muscle cells. Here we report the
      isolation and characterization of the human (h) NPR-B gene promoter. Using 5'
      rapid amplification of cDNA ends analysis, we have identified the 5' terminus of
      the hNPR-B gene transcript approximately 732 base pairs upstream from the
      presumed translation start site of the protein. We generated a series of 5'
      deletion mutants linked to a luciferase reporter and introduced these constructs
      into rat aortic smooth muscle cells or neonatal rat cardiac fibroblasts. Maximal
      expression was seen with a construct harboring 441 base pairs of 5' flanking
      sequence. Site-directed mutagenesis of the proximal promoter revealed a series of
      GC-rich sequences, 5 of which contributed modestly (approximately 25%) to basal
      hNPR-B promoter activity. Mutation of a sixth GC-rich sequence led to a >90%
      reduction in promoter activity. This sequence was shown to associate with Sp1 and
      Sp3 in vitro. The same mutation that resulted in loss of functional activity also
      resulted in loss of binding activity in vitro. Overexpression of Sp1 or Sp3 in
      Drosophila Schneider cells resulted in an increase in hNPR-B promoter activity
      that was completely nullified with the Sp1 binding site mutation described above.
      These studies provide the first description and characterization of the NPR-B
      gene promoter and suggest that this promoter's activity is dominated by a single
      cluster of Sp1-binding elements in the proximal 5' flanking sequence of the gene.

PMID- 15262908
TI  - Membrane trafficking of angiotensin receptor type-1 and mechanochemical signal
      transduction in proximal tubule cells.
AB  - Cellular localization and trafficking of the major angiotensin receptor, AT1, was
      studied in mouse proximal tubule cell lines because angiotensin II concentrations
      in the luminal fluid of proximal tubules are greater than the K(d) of the
      receptor and would predict high turnover rates of the receptor. Mouse proximal
      tubule cells can exist in 2 polarized, differentiated states after confluence: a
      protoepithelium and a highly differentiated epithelium. The latter is
      distinguished by greater polarization of the microtubule cytoskeleton and
      collection of apical microtubule-dependent membrane proteins in condensed apical
      recycling endosomes (CARE) in proximity to the primary cilium. AT1, AT2, and the
      sodium hydrogen exchanger NHE3 are localized to CARE. With fluid movement, AT1
      receptors externalize from CARE to the apical plasma membrane and allow luminal
      angiotensin II to initiate cell signaling. These data suggest that fluid movement
      controls receptor externalization and, hence, a model in which ciliary deflection
      results in transduction of a mechanical stimulus into the chemical signaling of
      the AT1 receptor.

PMID- 15262910
TI  - Cellular-free magnesium depletion in brain and muscle of normal and preeclamptic
      pregnancy: a nuclear magnetic resonance spectroscopic study.
AB  - Preeclampsia is a pregnancy disorder of unknown origin, characterized by
      vasospasm, elevated blood pressure, and increased neuromuscular irritability,
      features common to syndromes of magnesium deficiency. Evidence of serum and
      ionized magnesium metabolism disturbances have been observed in women with
      preeclampsia. This and the therapeutic utility of magnesium in preeclampsia led
      us to investigate the extent to which an endogenous tissue magnesium deficiency
      might be present in and contribute to its pathophysiology. We used (31)P nuclear
      magnetic resonance spectroscopy to noninvasively measure in situ intracellular
      free magnesium levels in brain and skeletal muscle of fasting nonpregnant women
      (n=12), and of third trimester women with uncomplicated pregnancies (n=11) and
      preeclampsia (n=7). Compared with nonpregnant controls (brain 519+/-59
      micromol/L; muscle 604+/-34 micromol/L), brain and skeletal muscle intracellular
      magnesium levels were significantly lower in both normal pregnant (brain 342+/-23
      micromol/L; muscle 482+/-40 micromol/L; P=0.05 for both tissues) and preeclamptic
      women (brain 229+/-17 micromol/L; muscle 433+/-46 micromol/L; P=0.05 for both
      tissues). Brain intracellular magnesium was further reduced in preeclamptics
      compared with normal pregnant subjects (P=0.05). For all pregnant subjects, blood
      pressure was significantly and inversely related to the concomitantly measured
      intracellular magnesium level in brain (systolic, r=-0.59, P=0.01; diastolic, r=
      0.52, P=0.02) but not in muscle. Cellular magnesium depletion is characteristic
      of normal pregnancy and may be one factor contributing to the pathophysiology of
      preeclampsia. Furthermore, the influence of central nervous system factors on
      blood pressure may be mediated, at least in part, by ambient intracellular
      magnesium levels.

PMID- 15262912
TI  - Nebivolol increases arterial distensibility in vivo.
AB  - Arterial stiffness is a key determinant of cardiovascular risk in hypertensive
      patients. beta-Blockers appear to be less effective than other drugs in improving
      outcome in hypertensive patients, and a potential explanation may be that beta
      blockers are less effective in reducing arterial stiffness. The aim of this study
      was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a
      robust measure of arterial distensibility, using a local, ovine, hind-limb model.
      In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but
      not atenolol, would increase arterial distensibility in vivo. All studies were
      conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure
      sensing catheter placed in the common iliac artery. Intraarterial infusion of
      nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter
      mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had
      no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3
      mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in
      PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of
      nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly
      attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also
      during coinfusion of butoxamine (P=0.02). These results demonstrate that
      nebivolol, but not atenolol, increases arterial distensibility. This effect of
      nebivolol is mediated through the release of NO via a beta2 adrenoceptor
      dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased
      large artery stiffness, such as isolated systolic hypertension.

PMID- 15262911
TI  - Visceral fat in hypertension: influence on insulin resistance and beta-cell
      function.
AB  - Preferential visceral adipose tissue (VAT) deposition has been associated with
      the presence of insulin resistance in obese and diabetic subjects. The
      independent association of VAT accumulation with hypertension and its impact on
      insulin sensitivity and beta-cell function have not been assessed. We measured
      VAT and subcutaneous fat depots by multiscan MRI in 13 nondiabetic men with newly
      detected, untreated essential hypertension (blood pressure=151+/-2/94+/-2 mm Hg,
      age=47+/-2 years, body mass index [BMI]=28.4+/-0.7 kg x m(-2)) and 26 age-matched
      and BMI-matched normotensive men (blood pressure=123+/-1/69+/-2 mm Hg). Insulin
      secretion was measured by deconvolution of C-peptide data obtained during an oral
      glucose tolerance test, and dynamic indices of beta-cell function were calculated
      by mathematical modeling. For a similar fat mass in the scanned abdominal region
      (4.8+/-0.3 versus 3.9+/-0.3 kg, hypertensive subjects versus controls, P=0.06),
      hypertensive subjects had 60% more VAT than controls (1.6+/-0.2 versus 1.0+/-0.1
      kg, P=0.003). Intrathoracic fat also was expanded in patients versus controls
      (45+/-5 versus 28+/-3 cm2, P=0.005). Insulin sensitivity was reduced (10.7+/-0.7
      versus 12.9+/-0.4 mL x min(-1) x kg(ffm)(-1), P=0.006), and total insulin output
      was proportionally increased (64 [21] versus 45 [24] nmol x m(-2). h, median
      [interquartile range], P=0.01), but dynamic indices of beta-cell function
      (glucose sensitivity, rate sensitivity, and potentiation) were similar in the 2
      groups. Abdominal VAT, insulin resistance, and blood pressure were quantitatively
      interrelated (rho's of 0.39 to 0.47, P<0.02 or less). In newly found, untreated
      men with essential hypertension, fat is preferentially accumulated
      intraabdominally and intrathoracically. Such visceral adiposity is quantitatively
      related to both height of blood pressure and severity of insulin resistance, but
      has no impact on the dynamics of beta-cell function.

PMID- 15262913
TI  - Vibrio cholerae biofilms: stuck between a rock and a hard place.

PMID- 15262914
TI  - Adaptive point mutation and adaptive amplification pathways in the Escherichia
      coli Lac system: stress responses producing genetic change.

PMID- 15262915
TI  - Rebuttal: adaptive point mutation (Rosenberg and Hastings).

PMID- 15262916
TI  - Rebuttal: adaptive point mutation (Rosenberg and Hastings).

PMID- 15262918
TI  - Rebuttal: adaptive mutation in Escherichia coli (Foster).

PMID- 15262917
TI  - Adaptive mutation in Escherichia coli.

PMID- 15262919
TI  - Rebuttal: adaptive mutation in Escherichia coli (Foster).

PMID- 15262921
TI  - Rebuttal: growth under selection stimulates Lac(+) reversion (Roth and
      Andersson).

PMID- 15262920
TI  - Adaptive mutation: how growth under selection stimulates Lac(+) reversion by
      increasing target copy number.

PMID- 15262922
TI  - Rebuttal: growth under selection stimulates Lac(+) reversion (Roth and
      Andersson).

PMID- 15262923
TI  - The sodium-driven flagellar motor controls exopolysaccharide expression in Vibrio
      cholerae.
AB  - Vibrio cholerae causes the life-threatening diarrheal disease cholera. This
      organism persists in aquatic environments in areas of endemicity, and it is
      believed that the ability of the bacteria to form biofilms in the environment
      contributes to their persistence. Expression of an exopolysaccharide (EPS),
      encoded by two vps gene clusters, is essential for biofilm formation and causes a
      rugose colonial phenotype. We previously reported that the lack of a flagellum
      induces V. cholerae EPS expression. To uncover the signaling pathway that links
      the lack of a flagellum to EPS expression, we introduced into a rugose flaA
      strain second-site mutations that would cause reversion back to the smooth
      phenotype. Interestingly, mutation of the genes encoding the sodium-driven motor
      (mot) in a nonflagellated strain reduces EPS expression, biofilm formation, and
      vps gene transcription, as does the addition of phenamil, which specifically
      inhibits the sodium-driven motor. Mutation of vpsR, which encodes a response
      regulator, also reduces EPS expression, biofilm formation, and vps gene
      transcription in nonflagellated cells. Complementation of a vpsR strain with a
      constitutive vpsR allele likely to mimic the phosphorylated state (D59E) restores
      EPS expression and biofilm formation, while complementation with an allele
      predicted to remain unphosphorylated (D59A) does not. Our results demonstrate the
      involvement of the sodium-driven motor and suggest the involvement of phospho
      VpsR in the signaling cascade that induces EPS expression. A nonflagellated
      strain expressing EPS is defective for intestinal colonization in the suckling
      mouse model of cholera and expresses reduced amounts of cholera toxin and toxin
      coregulated pili in vitro. Wild-type levels of virulence factor expression and
      colonization could be restored by a second mutation within the vps gene cluster
      that eliminated EPS biosynthesis. These results demonstrate a complex
      relationship between the flagellum-dependent EPS signaling cascade and virulence.

PMID- 15262924
TI  - Three different systems participate in L-cystine uptake in Bacillus subtilis.
AB  - The symporter YhcL and two ATP binding cassette transporters, YtmJKLMN and
      YckKJI, were shown to mediate L-cystine uptake in Bacillus subtilis. A triple
      DeltayhcL DeltaytmJKLMN DeltayckK mutant was unable to grow in the presence of L
      cystine and to take up L-cystine. We propose that yhcL, ytmJKLMN, and yckKJI
      should be renamed tcyP, tcyJKLMN, and tcyABC, respectively. The L-cystine uptake
      by YhcL (K(m) = 0.6 microM) was strongly inhibited by seleno-DL-cystine, while
      the transport due to the YtmJKLMN system (K(m) = 2.5 microM) also drastically
      decreased in the presence of DL-cystathionine, L-djenkolic acid, or S-methyl-L
      cysteine. Accordingly, a DeltaytmJKLMN mutant did not grow in the presence of 100
      microM DL-cystathionine, 100 microM L-djenkolic acid, or 100 microM S-methyl-L
      cysteine. The expression of the ytmI operon and the yhcL gene was regulated in
      response to sulfur availability, while the level of expression of the yckK gene
      remained low under all the conditions tested.

PMID- 15262925
TI  - Molecular cloning and characterization of Bifidobacterium bifidum 1,2-alpha-L
      fucosidase (AfcA), a novel inverting glycosidase (glycoside hydrolase family 95).
AB  - A genomic library of Bifidobacterium bifidum constructed in Escherichia coli was
      screened for the ability to hydrolyze the alpha-(1-->2) linkage of 2'
      fucosyllactose, and a gene encoding 1,2-alpha-l-fucosidase (AfcA) was isolated.
      The afcA gene was found to comprise 1,959 amino acid residues with a predicted
      molecular mass of 205 kDa and containing a signal peptide and a membrane anchor
      at the N and C termini, respectively. A domain responsible for fucosidase
      activity (the Fuc domain; amino acid residues 577 to 1474) was localized by
      deletion analysis and then purified as a hexahistidine-tagged protein. The
      recombinant Fuc domain specifically hydrolyzed the terminal alpha-(1-->2)
      fucosidic linkages of various oligosaccharides and a sugar chain of a
      glycoprotein. The stereochemical course of the hydrolysis of 2'-fucosyllactose
      was determined to be inversion by using (1)H nuclear magnetic resonance. The
      primary structure of the Fuc domain exhibited no similarity to those of any
      glycoside hydrolases (GHs) but showed high similarity to those of several
      hypothetical proteins in a database. Thus, it was revealed that the AfcA protein
      constitutes a novel inverting GH family (GH family 95).

PMID- 15262926
TI  - A novel p-nitrophenol degradation gene cluster from a gram-positive bacterium,
      Rhodococcus opacus SAO101.
AB  - p-Nitrophenol (4-NP) is recognized as an environmental contaminant; it is used
      primarily for manufacturing medicines and pesticides. To date, several 4-NP
      degrading bacteria have been isolated; however, the genetic information remains
      very limited. In this study, a novel 4-NP degradation gene cluster from a gram
      positive bacterium, Rhodococcus opacus SAO101, was identified and characterized.
      The deduced amino acid sequences of npcB, npcA, and npcC showed identity with
      phenol 2-hydroxylase component B (reductase, PheA2) of Geobacillus
      thermoglucosidasius A7 (32%), with 2,4,6-trichlorophenol monooxygenase (TcpA) of
      Ralstonia eutropha JMP134 (44%), and with hydroxyquinol 1,2-dioxygenase (ORF2) of
      Arthrobacter sp. strain BA-5-17 (76%), respectively. The npcB, npcA, and npcC
      genes were cloned into pET-17b to construct the respective expression vectors
      pETnpcB, pETnpcA, and pETnpcC. Conversion of 4-NP was observed when a mixture of
      crude cell extracts of Escherichia coli containing pETnpcB and pETnpcA was used
      in the experiment. The mixture converted 4-NP to hydroxyquinol and also converted
      4-nitrocatechol (4-NCA) to hydroxyquinol. Furthermore, the crude cell extract of
      E. coli containing pETnpcC converted hydroxyquinol to maleylacetate. These
      results suggested that npcB and npcA encode the two-component 4-NP/4-NCA
      monooxygenase and that npcC encodes hydroxyquinol 1,2-dioxygenase. The npcA and
      npcC mutant strains, SDA1 and SDC1, completely lost the ability to grow on 4-NP
      as the sole carbon source. These results clearly indicated that the cloned npc
      genes play an essential role in 4-NP mineralization in R. opacus SAO101.

PMID- 15262927
TI  - Ribosomal protein S1 specifically binds to the 5' untranslated region of the
      Pseudomonas aeruginosa stationary-phase sigma factor rpoS mRNA in the logarithmic
      phase of growth.
AB  - The rpoS gene encodes the stationary-phase sigma factor (RpoS or sigma(s)), which
      was identified in several gram-negative bacteria as a central regulator
      controlling the expression of genes involved in cell survival in response to
      cessation of growth (stationary phase) and providing cross-protection against
      various stresses. In Pseudomonas aeruginosa, the levels of sigma(s) increase
      dramatically at the onset of the stationary phase and are regulated at the
      transcriptional and posttranscriptional levels. The P. aeruginosa rpoS gene is
      transcribed as a monocistronic rpoS mRNA transcript comprised of an unusually
      long 373-bp 5' untranslated region (5' UTR). In this study, the 5' UTR and total
      protein extracts from P. aeruginosa logarithmic and stationary phases of growth
      were used in order to investigate the protein-RNA interactions that may modulate
      the translational process. It was observed that a 69-kDa protein, which
      corresponded to ribosomal protein S1, preferentially binds the 5' UTR of the rpoS
      mRNA in the logarithmic phase and not in the stationary phase. This is the first
      report of a protein-rpoS mRNA 5' UTR interaction in P. aeruginosa, and the
      possible involvement of protein S1 in translation regulation of rpoS is
      discussed.

PMID- 15262928
TI  - PspG, a new member of the Yersinia enterocolitica phage shock protein regulon.
AB  - The Yersinia enterocolitica phage shock protein (Psp) system is induced when the
      Ysc type III secretion system is produced or when only the YscC secretin
      component is synthesized. Some psp null mutants have a growth defect when YscC is
      produced and a severe virulence defect in animals. The Y. enterocolitica psp
      locus is made up of two divergently transcribed cistrons, pspF and pspABCDycjXF.
      pspA operon expression is dependent on RpoN (sigma(54)) and the enhancer-binding
      protein PspF. Previous data indicated that PspF also controls at least one gene
      that is not part of the psp locus. In this study we describe the identification
      of pspG, a new member of the PspF regulon. Predicted RpoN-binding sites upstream
      of the pspA genes from different bacteria have a common divergence from the
      consensus sequence, which may be a signature of PspF-dependent promoters. The Y.
      enterocolitica pspG gene was identified because its promoter also has this
      signature. Like the pspA operon, pspG is positively regulated by PspF, negatively
      regulated by PspA, and induced in response to the production of secretins.
      Purified His(6)-PspF protein specifically interacts with the pspA and pspG
      control regions. A pspA operon deletion mutant has a growth defect when the YscC
      secretin is produced and a virulence defect in a mouse model of infection. These
      phenotypes were exacerbated by a pspG null mutation. Therefore, PspG is the
      missing component of the Y. enterocolitica Psp regulon that was previously
      predicted to exist.

PMID- 15262929
TI  - Systematic mutagenesis of the Escherichia coli genome.
AB  - A high-throughput method has been developed for the systematic mutagenesis of the
      Escherichia coli genome. The system is based on in vitro transposition of a
      modified Tn5 element, the Sce-poson, into linear fragments of each open reading
      frame. The transposon introduces both positive (kanamycin resistance) and
      negative (I-SceI recognition site) selectable markers for isolation of mutants
      and subsequent allele replacement, respectively. Reaction products are then
      introduced into the genome by homologous recombination via the lambdaRed
      proteins. The method has yielded insertion alleles for 1976 genes during a first
      pass through the genome including, unexpectedly, a number of known and putative
      essential genes. Sce-poson insertions can be easily replaced by markerless
      mutations by using the I-SceI homing endonuclease to select against retention of
      the transposon as demonstrated by the substitution of amber and/or in-frame
      deletions in six different genes. This allows a Sce-poson-containing gene to be
      specifically targeted for either designed or random modifications, as well as
      permitting the stepwise engineering of strains with multiple mutations. The
      promiscuous nature of Tn5 transposition also enables a targeted gene to be
      dissected by using randomly inserted Sce-posons as shown by a lacZ allelic
      series. Finally, assessment of the insertion sites by an iterative weighted
      matrix algorithm reveals that these hyperactive Tn5 complexes generally recognize
      a highly degenerate asymmetric motif on one end of the target site helping to
      explain the randomness of Tn5 transposition.

PMID- 15262930
TI  - Fibronectin binding to the Salmonella enterica serotype Typhimurium ShdA
      autotransporter protein is inhibited by a monoclonal antibody recognizing the A3
      repeat.
AB  - ShdA is a large outer membrane protein of the autotransporter family whose
      passenger domain binds the extracellular matrix proteins fibronectin and collagen
      I, possibly by mimicking the host ligand heparin. The ShdA passenger domain
      consists of approximately 1,500 amino acid residues that can be divided into two
      regions based on features of the primary amino acid sequence: an N-terminal
      nonrepeat region followed by a repeat region composed of two types of imperfect
      direct amino acid repeats, called type A and type B. The repeat region bound
      bovine fibronectin with an affinity similar to that for the complete ShdA
      passenger domain, while the nonrepeat region exhibited comparatively low
      fibronectin-binding activity. A number of fusion proteins containing truncated
      fragments of the repeat region did not bind bovine fibronectin. However, binding
      of the passenger domain to fibronectin was inhibited in the presence of immune
      serum raised to one truncated fragment of the repeat region that contained
      repeats A2, B8, A3, and B9. Furthermore, a monoclonal antibody that specifically
      recognized an epitope in a recombinant protein containing the A3 repeat inhibited
      binding of ShdA to fibronectin.

PMID- 15262931
TI  - Two biosynthetic pathways for aromatic amino acids in the archaeon Methanococcus
      maripaludis.
AB  - Methanococcus maripaludis is a strictly anaerobic, methane-producing archaeon.
      Aromatic amino acids (AroAAs) are biosynthesized in this autotroph either by the
      de novo pathway, with chorismate as an intermediate, or by the incorporation of
      exogenous aryl acids via indolepyruvate oxidoreductase (IOR). In order to
      evaluate the roles of these pathways, the gene that encodes the third step in the
      de novo pathway, 3-dehydroquinate dehydratase (DHQ), was deleted. This mutant
      required all three AroAAs for growth, and no DHQ activity was detectible in cell
      extracts, compared to 6.0 +/- 0.2 mU mg(-1) in the wild-type extract. The growth
      requirement for the AroAAs could be fulfilled by the corresponding aryl acids
      phenylacetate, indoleacetate, and p-hydroxyphenylacetate. The specific
      incorporation of phenylacetate into phenylalanine by the IOR pathway was
      demonstrated in vivo by labeling with [1-(13)C]phenylacetate. M. maripaludis has
      two IOR homologs. A deletion mutant for one of these homologs contained 76, 74,
      and 42% lower activity for phenylpyruvate, p-hydoxyphenylpyruvate, and
      indolepyruvate oxidation, respectively, than the wild type. Growth of this mutant
      in minimal medium was inhibited by the aryl acids, but the AroAAs partially
      restored growth. Genetic complementation of the IOR mutant also restored much of
      the wild-type phenotype. Thus, aryl acids appear to regulate the expression or
      activity of the de novo pathway. The aryl acids did not significantly inhibit the
      activity of the biosynthetic enzymes chorismate mutase, prephenate dehydratase,
      and prephenate dehydrogenase in cell extracts, so the inhibition of growth was
      probably not due to an effect on these enzymes.

PMID- 15262932
TI  - Characterization of the 3-O-methylgallate dioxygenase gene and evidence of
      multiple 3-O-methylgallate catabolic pathways in Sphingomonas paucimobilis SYK-6.
AB  - Sphingomonas paucimobilis SYK-6 is able to grow on various lignin-derived biaryls
      as the sole source of carbon and energy. These compounds are degraded to
      vanillate and syringate by the unique and specific enzymes in this strain.
      Vanillate and syringate are converted to protocatechuate (PCA) and 3-O
      methylgallate (3MGA), respectively, by the tetrahydrofolate-dependent O
      demethylases. Previous studies have suggested that these compounds are further
      degraded via the PCA 4,5-cleavage pathway. However, our subsequent analysis of
      the ligB insertion mutant, which encodes the beta subunit of PCA 4,5-dioxygenase,
      suggested that at least one alternative route is involved in 3MGA degradation. In
      the present study, we isolated the desZ gene, which confers 3MGA degradation
      activity on Escherichia coli. The deduced amino acid sequence of desZ showed ca.
      20 to 43% identity with the type II extradiol dioxygenases. Gas chromatography
      mass spectrometry analysis suggested that DesZ catalyzes the 3,4-cleavage of
      3MGA. Disruption of both desZ and ligB in SYK-6 resulted in loss of the dioxygen
      dependent 3MGA transformation activity, but the resulting mutant retained the
      ability to grow on syringate. We found that the cell extract of the desZ ligB
      double mutant was able to convert 3MGA to gallate when tetrahydrofolate was added
      to the reaction mixture, and the cell extract of this mutant degraded gallate to
      the same degree as the wild type did. All these results suggest that syringate is
      degraded through multiple 3MGA degradation pathways in which ligAB, desZ, 3MGA O
      demethylase, and gallate dioxygenase are participants.

PMID- 15262933
TI  - Identification of the protease and the turnover signal responsible for cell cycle
      dependent degradation of the Caulobacter FliF motor protein.
AB  - Flagellar ejection is tightly coupled to the cell cycle in Caulobacter
      crescentus. The MS ring protein FliF, which anchors the flagellar structure in
      the inner membrane, is degraded coincident with flagellar release. Previous work
      showed that removal of 26 amino acids from the C terminus of FliF prevents
      degradation of the protein and interferes with flagellar assembly. To understand
      FliF degradation in more detail, we identified the protease responsible for FliF
      degradation and performed a high-resolution mutational analysis of the C-terminal
      degradation signal of FliF. Cell cycle-dependent turnover of FliF requires an
      intact clpA gene, suggesting that the ClpAP protease is required for removal of
      the MS ring protein. Deletion analysis of the entire C-terminal cytoplasmic
      portion of FliF C confirmed that the degradation signal was contained in the last
      26 amino acids that were identified previously. However, only deletions longer
      than 20 amino acids led to a stable FliF protein, while shorter deletions
      dispersed over the entire 26 amino acids critical for turnover had little effect
      on stability. This indicated that the nature of the degradation signal is not
      based on a distinct primary amino acid sequence. The addition of charged amino
      acids to the C-terminal end abolished cell cycle-dependent FliF degradation,
      implying that a hydrophobic tail feature is important for the degradation of
      FliF. Consistent with this, ClpA-dependent degradation was restored when a short
      stretch of hydrophobic amino acids was added to the C terminus of stable FliF
      mutant forms.

PMID- 15262934
TI  - Circadian rhythms in the thermophilic cyanobacterium Thermosynechococcus
      elongatus: compensation of period length over a wide temperature range.
AB  - Proteins derived from the thermophilic cyanobacterium Thermosynechococcus
      elongatus BP-1, which performs plant-type oxygenic photosynthesis, are suitable
      for biochemical, biophysical, and X-ray crystallographic studies. We developed an
      automated bioluminescence real-time monitoring system for the circadian clock in
      the thermophilic cyanobacterium T. elongatus BP-1 that uses a bacterial
      luciferase gene set (Xl luxAB) derived from Xenorhabdus luminescens as a
      bioluminescence reporter gene. A promoter region of the psbA1 gene of T.
      elongatus was fused to the Xl luxAB gene set and inserted into a specific
      targeting site in the genome of T. elongatus. The bioluminescence from the cells
      of the psbA1-reporting strain was measured by an automated monitoring apparatus
      with photomultiplier tubes. The strain exhibited the circadian rhythms of
      bioluminescence with a 25-h period length for at least 10 days in constant light
      and temperature. The rhythms were reset by light-dark cycle, and their period
      length was almost constant over a wide range of temperatures (30 to 60 degrees
      C). Theses results indicate that T. elongatus has the circadian clock that is
      widely temperature compensated.

PMID- 15262935
TI  - 6S RNA function enhances long-term cell survival.
AB  - 6S RNA was identified in Escherichia coli >30 years ago, but the physiological
      role of this RNA has remained elusive. Here, we demonstrate that 6S RNA-deficient
      cells are at a disadvantage for survival in stationary phase, a time when 6S RNA
      regulates transcription. Growth defects were most apparent as a decrease in the
      competitive fitness of cells lacking 6S RNA. To decipher the molecular mechanisms
      underlying the growth defects, we have expanded studies of 6S RNA effects on
      transcription. 6S RNA inhibition of sigma(70)-dependent transcription was not
      ubiquitous, in spite of the fact that the vast majority of sigma(70)-RNA
      polymerase is bound by 6S RNA during stationary phase. The sigma(70)-dependent
      promoters inhibited by 6S RNA contain an extended -10 promoter element,
      suggesting that this feature may define a class of 6S RNA-regulated genes. We
      also discovered a secondary effect of 6S RNA in the activation of sigma(S)
      dependent transcription at several promoters. We conclude that 6S RNA regulation
      of both sigma(70) and sigma(S) activities contributes to increased cell
      persistence during nutrient deprivation.

PMID- 15262936
TI  - The global regulator genes from biocontrol strain Serratia plymuthica IC1270:
      cloning, sequencing, and functional studies.
AB  - The biocontrol activity of various fluorescent pseudomonads towards plant
      pathogenic fungi is dependent upon the GacA/GacS-type two-component system of
      global regulators and the RpoS transcription sigma factor. In particular, these
      components are required for the production of antifungal antibiotics and
      exoenzymes. To investigate the effects of these global regulators on the
      expression of biocontrol factors by plant-associated bacteria other than
      Pseudomonas spp., gacA/gacS and rpoS homologues were cloned from biocontrol
      strain IC1270 of Serratia plymuthica, which produces a set of antifungal
      compounds, including chitinolytic enzymes and the antibiotic pyrrolnitrin. The
      nucleotide and deduced protein sequence alignments of the cloned gacA/gacS-like
      genes-tentatively designated grrA (global response regulation activator) and grrS
      (global response regulation sensor) and of the cloned rpoS gene revealed 64 to
      93% identity with matching genes and proteins of the enteric bacteria Escherichia
      coli, Pectobacterium carotovora subsp. carotovora, and Serratia marcescens. grrA,
      grrS, and rpoS gene replacement mutants of strain IC1270 were deficient in the
      production of pyrrolnitrin, an exoprotease, and N-acylhomoserine lactone quorum
      sensing signal molecules. However, neither mutant appeared to differ from the
      parental strain in the production of siderophores, and only grrA and grrS mutants
      were deficient in the production of a 58-kDa endochitinase, representing the
      involvement of other sigma factors in the regulation of strain IC1270's
      chitinolytic activity. Compared to the parental strain, the grrA, grrS, and rpoS
      mutants were markedly less capable of suppressing Rhizoctonia solani and Pythium
      aphanidermatum under greenhouse conditions, indicating the dependence of strain
      IC1270's biocontrol property on the GrrA/GrrS and RpoS global regulators.

PMID- 15262937
TI  - Intraspecific phylogeny and lineage group identification based on the prfA
      virulence gene cluster of Listeria monocytogenes.
AB  - Listeria monocytogenes is a serious food-borne pathogen that can cause invasive
      disease in humans and other animals and has been the leading cause of food
      recalls due to microbiological concerns in recent years. In order to test
      hypotheses regarding L. monocytogenes lineage composition, evolution, ecology,
      and taxonomy, a robust intraspecific phylogeny was developed based on prfA
      virulence gene cluster sequences from 113 L. monocytogenes isolates. The results
      of the multigene phylogenetic analyses confirm that L. monocytogenes comprises at
      least three evolutionary lineages, demonstrate that lineages most frequently
      (lineage 1) and least frequently (lineage 3) associated with human listeriosis
      are sister-groups, and reveal for the first time that the human epidemic
      associated serotype 4b is prevalent among strains from lineage 1 and lineage 3.
      In addition, a PCR-based test for lineage identification was developed and used
      in a survey of food products demonstrating that the low frequency of association
      between lineage 3 isolates and human listeriosis cases likely reflects rarity of
      exposure and not reduced virulence for humans as has been previously suggested.
      However, prevalence data do suggest lineage 3 isolates may be better adapted to
      the animal production environment than the food-processing environment. Finally,
      analyses of haplotype diversity indicate that lineage 1 has experienced a purge
      of genetic variation that was not observed in the other lineages, suggesting that
      the three L. monocytogenes lineages may represent distinct species within the
      framework of the cohesion species concept.

PMID- 15262938
TI  - Replication of Enterococcus faecalis pheromone-responding plasmid pAD1: location
      of the minimal replicon and oriV site and RepA involvement in initiation of
      replication.
AB  - The hemolysin-determining plasmid pAD1 is a member of a widely disseminated
      family of highly conjugative elements commonly present in clinical isolates of
      Enterococcus faecalis. The determinants repA, repB, and repC, as well as adjacent
      iteron sequences, are believed to play important roles in pAD1 replication and
      maintenance. The repA gene encodes an initiator protein, whereas repB and repC
      encode proteins related to stability and copy number. The present study focuses
      specifically on repA and identifies a replication origin (oriV) within a central
      region of the repA determinant. A small segment of repA carrying oriV was able to
      support replication in cis of a plasmid vector otherwise unable to replicate, if
      an intact RepA was supplied in trans. We demonstrate that under conditions in
      which RepA is expressed from an artificial promoter, a segment of DNA carrying
      only repA is sufficient for stable replication in E. faecalis. We also show that
      RepA binds specifically to oriV DNA at several sites containing inverted repeat
      sequences (i.e., IR-1) and nonspecifically to single-stranded DNA, and related
      genetic analyses confirm that these sequences play an important role in
      replication. Finally, we reveal a relationship between the internal structure of
      RepA and its ability to recognize oriV. An in-frame deletion within repA
      resulting in loss of 105 nucleotides, including at least part of oriV, did not
      eliminate the ability of the altered RepA protein to initiate replication using
      an intact origin provided in trans. The relationship of RepA to other known
      initiator proteins is also discussed.

PMID- 15262939
TI  - Induction of a novel class of diacylglycerol acyltransferases and triacylglycerol
      accumulation in Mycobacterium tuberculosis as it goes into a dormancy-like state
      in culture.
AB  - Mycobacterium tuberculosis enters the host by inhalation of an infectious aerosol
      and replicates in the alveolar macrophages until the host's immune defense causes
      bacteriostasis, which leads the pathogen to go into nonreplicative drug-resistant
      dormancy. The dormant pathogen can survive for decades till the host's immune
      system is weakened and active tuberculosis develops. Even though fatty acids are
      thought to be the major energy source required for the persistence phase, the
      source of fatty acids used is not known. We postulate that the pathogen uses
      triacylglycerol (TG) as a storage form of fatty acids. Little is known about the
      biosynthesis of TG in M. tuberculosis. We show that 15 mycobacterial genes that
      we identified as putative triacylglycerol synthase (tgs) when expressed in
      Escherichia coli showed TGS activity, and we report some basic catalytic
      characteristics of the most active enzymes. We show that several tgs genes are
      induced when the pathogen goes into the nonreplicative drug-resistant state
      caused by slow withdrawal of O(2) and also by NO treatment, which is known to
      induce dormancy-associated genes. The gene (Rv3130c) that shows the highest TGS
      activity when expressed in E. coli shows the highest induction by hypoxia and NO
      treatment. Biochemical evidence shows that TG synthesis and accumulation occur
      under both conditions. We conclude that TG may be a form of energy storage for
      use during long-term dormancy. Therefore, TG synthesis may be an appropriate
      target for novel antilatency drugs that can prevent the organism from surviving
      dormancy and thus assist in the control of tuberculosis.

PMID- 15262940
TI  - A type II protein secretory pathway required for levansucrase secretion by
      Gluconacetobacter diazotrophicus.
AB  - The endophytic diazotroph Gluconacetobacter diazotrophicus secretes a
      constitutively expressed levansucrase (LsdA, EC 2.4.1.10) to utilize plant
      sucrose. LsdA, unlike other extracellular levansucrases from gram-negative
      bacteria, is transported to the periplasm by a signal-peptide-dependent pathway.
      We identified an unusually organized gene cluster encoding at least the
      components LsdG, -O, -E, -F, -H, -I, -J, -L, -M, -N, and -D of a type II
      secretory system required for LsdA translocation across the outer membrane.
      Another open reading frame, designated lsdX, is located between the operon
      promoter and lsdG, but it was not identified in BLASTX searches of the
      DDBJ/EMBL/GenBank databases. The lsdX, -G, and -O genes were isolated from a
      cosmid library of strain SRT4 by complementation of an ethyl methanesulfonate
      mutant unable to transport LsdA across the outer membrane. The downstream genes
      lsdE, -F, -H, -I, -J, -L, -M, -N, and -D were isolated through chromosomal
      walking. The high G+C content (64 to 74%) and the codon usage of the genes
      identified are consistent with the G+C content and codon usage of the standard G.
      diazotrophicus structural gene. Sequence analysis of the gene cluster indicated
      that a polycistronic transcript is synthesized. Targeted disruption of lsdG,
      lsdO, or lsdF blocked LsdA secretion, and the bacterium failed to grow on
      sucrose. Replacement of Cys(162) by Gly at the C terminus of the pseudopilin LsdG
      abolished the protein functionality, suggesting that there is a relationship with
      type IV pilins. Restriction fragment length polymorphism analysis revealed
      conservation of the type II secretion operon downstream of the levansucrase
      levanase (lsdA-lsdB) locus in 14 G. diazotrophicus strains representing 11
      genotypes recovered from four different host plants in diverse geographical
      regions. To our knowledge, this is the first report of a type II pathway for
      protein secretion in the Acetobacteraceae.

PMID- 15262941
TI  - Comparative whole-genome hybridization reveals genomic islands in Brucella
      species.
AB  - Brucella species are responsible for brucellosis, a worldwide zoonotic disease
      causing abortion in domestic animals and Malta fever in humans. Based on host
      preference, the genus is divided into six species. Brucella abortus, B.
      melitensis, and B. suis are pathogenic to humans, whereas B. ovis and B. neotomae
      are nonpathogenic to humans and B. canis human infections are rare. Limited
      genome diversity exists among Brucella species. Comparison of Brucella species
      whole genomes is, therefore, likely to identify factors responsible for
      differences in host preference and virulence restriction. To facilitate such
      studies, we used the complete genome sequence of B. melitensis 16M, the species
      highly pathogenic to humans, to construct a genomic microarray. Hybridization of
      labeled genomic DNA from Brucella species to this microarray revealed a total of
      217 open reading frames (ORFs) altered in five Brucella species analyzed. These
      ORFs are often found in clusters (islands) in the 16M genome. Examination of the
      genomic context of these islands suggests that many are horizontally acquired.
      Deletions of genetic content identified in Brucella species are conserved in
      multiple strains of the same species, and genomic islands missing in a given
      species are often restricted to that particular species. These findings suggest
      that, whereas the loss or gain of genetic material may be related to the host
      range and virulence restriction of certain Brucella species for humans,
      independent mechanisms involving gene inactivation or altered expression of
      virulence determinants may also contribute to these differences.

PMID- 15262942
TI  - Three-dimensional electron microscopic imaging of membrane invaginations in
      Escherichia coli overproducing the chemotaxis receptor Tsr.
AB  - Electron tomography is a powerful method for determining the three-dimensional
      structures of large macromolecular assemblies, such as cells, organelles, and
      multiprotein complexes, when crystallographic averaging methods are not
      applicable. Here we used electron tomographic imaging to determine the molecular
      architecture of Escherichia coli cells engineered to overproduce the bacterial
      chemotaxis receptor Tsr. Tomograms constructed from fixed, cryosectioned cells
      revealed that overproduction of Tsr led to formation of an extended internal
      membrane network composed of stacks and extended tubular structures. We present
      an interpretation of the tomogram in terms of the packing arrangement of Tsr
      using constraints derived from previous X-ray and electron-crystallographic
      studies of receptor clusters. Our results imply that the interaction between the
      cytoplasmic ends of Tsr is likely to stabilize the presence of the membrane
      networks in cells overproducing Tsr. We propose that membrane invaginations that
      are potentially capable of supporting axial interactions between receptor
      clusters in apposing membranes could also be present in wild-type E. coli and
      that such receptor aggregates could play an important role in signal transduction
      during bacterial chemotaxis.

PMID- 15262943
TI  - The homogentisate pathway: a central catabolic pathway involved in the
      degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in
      Pseudomonas putida.
AB  - Pseudomonas putida metabolizes Phe and Tyr through a peripheral pathway involving
      hydroxylation of Phe to Tyr (PhhAB), conversion of Tyr into 4
      hydroxyphenylpyruvate (TyrB), and formation of homogentisate (Hpd) as the central
      intermediate. Homogentisate is then catabolized by a central catabolic pathway
      that involves three enzymes, homogentisate dioxygenase (HmgA),
      fumarylacetoacetate hydrolase (HmgB), and maleylacetoacetate isomerase (HmgC),
      finally yielding fumarate and acetoacetate. Whereas the phh, tyr, and hpd genes
      are not linked in the P. putida genome, the hmgABC genes appear to form a single
      transcriptional unit. Gel retardation assays and lacZ translational fusion
      experiments have shown that hmgR encodes a specific repressor that controls the
      inducible expression of the divergently transcribed hmgABC catabolic genes, and
      homogentisate is the inducer molecule. Footprinting analysis revealed that HmgR
      protects a region in the Phmg promoter that spans a 17-bp palindromic motif and
      an external direct repetition from position -16 to position 29 with respect to
      the transcription start site. The HmgR protein is thus the first IclR-type
      regulator that acts as a repressor of an aromatic catabolic pathway. We
      engineered a broad-host-range mobilizable catabolic cassette harboring the
      hmgABC, hpd, and tyrB genes that allows heterologous bacteria to use Tyr as a
      unique carbon and energy source. Remarkably, we show here that the catabolism of
      3-hydroxyphenylacetate in P. putida U funnels also into the homogentisate central
      pathway, revealing that the hmg cluster is a key catabolic trait for
      biodegradation of a small number of aromatic compounds.

PMID- 15262944
TI  - Secretion and function of Salmonella SPI-2 effector SseF require its chaperone,
      SscB.
AB  - Salmonella strains utilize a type III secretion system for their successful
      survival and replications inside host cells. SseF is one of the several effector
      proteins that are required for conferring this survival ability by altering the
      trafficking of the Salmonella-containing vacuoles. These effector proteins often
      require appropriate chaperones to maintain their stabilities inside the bacteria.
      These chaperones are also known to assist the subsequent secretion and
      translocation of their substrates. We report here that SscB acts as the chaperone
      for SseF, an effector for the Salmonella pathogenicity island 2 (SPI-2). We found
      that the sscB gene is required for the formation of Salmonella sp.-induced
      continuous filaments in epithelial cells. Efficient Salmonella replication in
      macrophages requires SscB function. Intracellular and secretion levels of SseF
      are greatly reduced in an sscB mutant strain compared to the wild-type strain. A
      protein stability assay demonstrated that the half-life of SseF is significantly
      shortened in the absence of SscB. Transcriptional analysis of the sseF gene
      showed that the effect of SscB on the SseF level is not at the transcriptional
      level. A coprecipitation experiment indicated that SscB interacts with SseF. In
      summary, our results indicate that SscB is a chaperone for SPI-2 effector SseF to
      facilitate its secretion and function inside the host cells.

PMID- 15262945
TI  - A movable surface: formation of Yersinia sp. biofilms on motile Caenorhabditis
      elegans.
AB  - Bubonic plague is transmitted by fleas whose feeding is blocked by a mass of
      Yersinia pestis in the digestive tract. Y. pestis and the closely related Y.
      pseudotuberculosis also block the feeding of Caenorhabditis elegans by forming a
      biofilm on the nematode head. C. elegans mutants with severe motility defects
      acquire almost no biofilm, indicating that normal animals accumulate the biofilm
      matrix as they move through a Yersinia lawn. Using the lectin wheat germ
      agglutinin as a probe, we show that the matrix on C. elegans contains
      carbohydrate produced by Yersinia. The carbohydrate is present in bacterial lawns
      prior to addition of nematodes, indicating that biofilm formation does not
      involve signaling between the two organisms. Furthermore, biofilm accumulation
      depends on continuous C. elegans exposure to a lawn of Yersinia bacteria.

PMID- 15262946
TI  - A second lysine-specific serine protease from Lysobacter sp. strain IB-9374.
AB  - A second lysyl endopeptidase gene (lepB) was found immediately upstream of the
      previously isolated lepA gene encoding a highly active lysyl endopeptidase in
      Lysobacter genomic DNA. The lepB gene consists of 2,034 nucleotides coding for a
      protein of 678 amino acids. Amino acid sequence alignment between the lepA and
      lepB gene products (LepA and LepB) revealed that the LepB precursor protein is
      composed of a prepeptide (20 amino acids [aa]), a propeptide (184 aa), a mature
      enzyme (274 aa), and a C-terminal extension peptide (200 aa). The mature enzyme
      region exhibited 72% sequence identity to its LepA counterpart and conserved all
      essential amino acids constituting the catalytic triad and the primary
      determining site for lysine specificity. The lepB gene encoding the propeptide
      and mature-enzyme portions was overexpressed in Escherichia coli, and the
      inclusion body produced generated active LepB through appropriate refolding and
      processing. The purified enzyme, a mature 274-aa lysine-specific endopeptidase,
      was less active and more sensitive to both temperature and denaturation with
      urea, guanidine hydrochloride, or sodium dodecyl sulfate than LepA. LepA-based
      modeling implies that LepB can fold into essentially the same three-dimensional
      structure as LepA by placing a peptide segment, composed of several inserted
      amino acids found only in LepB, outside the molecule and that the Tyr169 side
      chain occupies the site in which the indole ring of Trp169, a built-in modulator
      for unique peptidase functions of LepA, resides. The results suggest that LepB is
      an isozyme of LepA and probably has a tertiary structure quite similar to it.

PMID- 15262947
TI  - Nucleotide sequence and evolution of the five-plasmid complement of the
      phytopathogen Pseudomonas syringae pv. maculicola ES4326.
AB  - Plasmids are transmissible, extrachromosomal genetic elements that are often
      responsible for environmental or host-specific adaptations. In order to identify
      the forces driving the evolution of these important molecules, we determined the
      complete nucleotide sequence of the five-plasmid complement of the radish and
      Arabidopsis pathogen Pseudomonas syringae pv. maculicola ES4326 and conducted an
      intraspecific comparative genomic analysis. To date, this is the most complex
      fully sequenced plasmid complement of any gram-negative bacterium. The plasmid
      complement comprises two pPT23A-like replicons, pPMA4326A (46,697 bp) and
      pPMA4326B (40,110 bp); a pPS10-like replicon, pPMA4326C (8,244 bp); and two
      atypical, replicase-deficient replicons, pPMA4326D (4,833 bp) and pPMA4326E
      (4,217 bp). A complete type IV secretion system is found on pPMA4326A, while the
      type III secreted effector hopPmaA is present on pPMA4326B. The region around
      hopPmaA includes a shorter hopPmaA homolog, insertion sequence (IS) elements, and
      a three-element cassette composed of a resolvase, an integrase, and an exeA gene
      that is also present in several human pathogens. We have also identified a novel
      genetic element (E622) that is present on all but the smallest plasmid
      (pPMA4326E) that has features of an IS element but lacks an identifiable
      transposase. This element is associated with virulence-related genes found in a
      wide range of P. syringae strains. Comparative genomic analyses of these and
      other P. syringae plasmids suggest a role for recombination and integrative
      elements in driving plasmid evolution.

PMID- 15262948
TI  - Cloning Serratia entomophila antifeeding genes--a putative defective prophage
      active against the grass grub Costelytra zealandica.
AB  - Serratia entomophila and Serratia proteamaculans (Enterobacteriaceae) cause amber
      disease in the grass grub Costelytra zealandica (Coleoptera: Scarabaeidae), an
      important pasture pest in New Zealand. Larval disease symptoms include cessation
      of feeding, clearance of the gut, amber coloration, and eventual death. A 155-kb
      plasmid, pADAP, carries the genes sepA, sepB, and sepC, which are essential for
      production of amber disease symptoms. Transposon insertions in any of the sep
      genes in pADAP abolish gut clearance but not cessation of feeding, indicating the
      presence of an antifeeding gene(s) elsewhere on pADAP. Based on deletion analysis
      of pADAP and subsequent sequence data, a 47-kb clone was constructed, which when
      placed in either an Escherichia coli or a Serratia background exerted strong
      antifeeding activity and often led to rapid death of the infected grass grub
      larvae. Sequence data show that the antifeeding component is part of a large gene
      cluster that may form a defective prophage and that six potential members of this
      prophage are present in Photorhabdus luminescens subsp. laumondii TTO1, a species
      which also has sep gene homologues.

PMID- 15262949
TI  - The phosphoenolpyruvate carboxylase from Methanothermobacter thermautotrophicus
      has a novel structure.
AB  - In Methanothermobacter thermautotrophicus, oxaloacetate synthesis is a major and
      essential CO(2)-fixation reaction. This methanogenic archaeon possesses two
      oxaloacetate-synthesizing enzymes, pyruvate carboxylase and phosphoenolpyruvate
      carboxylase. The phosphoenolpyruvate carboxylase from this organism was purified
      to homogeneity. The subunit size of this homotetrameric protein was 55 kDa, which
      is about half that of all known bacterial and eukaryotic phosphoenolpyruvate
      carboxylases (PPCs). The NH(2)-terminal sequence identified this enzyme as the
      product of MTH943, an open reading frame with no assigned function in the genome
      sequence. A BLAST search did not show an obvious sequence similarity between
      MTH943 and known PPCs, which are generally well conserved. This is the first
      report of a new type of phosphoenolpyruvate carboxylase that we call PpcA ("A"
      for "archaeal"). Homologs to PpcA were present in most archaeal genomic
      sequences, but only in three bacterial (Clostridium perfringens, Oenococcus oeni,
      and Leuconostoc mesenteroides) and no eukaryotic genomes. PpcA was the only
      recognizable oxaloacetate-producing enzyme in Methanopyrus kandleri, a
      hydrothermal vent organism. Each PpcA-containing organism lacked a PPC homolog.
      The activity of M. thermautotrophicus PpcA was not influenced by acetyl coenzyme
      A and was about 50 times less sensitive to aspartate than the Escherichia coli
      PPC. The catalytic core (including His(138), Arg(587), and Gly(883)) of the E.
      coli PPC was partly conserved in PpcA, but three of four aspartate-binding
      residues (Lys(773), Arg(832), and Asn(881)) were not. PPCs probably evolved from
      PpcA through a process that added allosteric sites to the enzyme. The reverse is
      also equally possible.

PMID- 15262950
TI  - DNA microarray analysis of genome dynamics in Yersinia pestis: insights into
      bacterial genome microevolution and niche adaptation.
AB  - Genomics research provides an unprecedented opportunity for us to probe into the
      pathogenicity and evolution of the world's most deadly pathogenic bacterium,
      Yersinia pestis, in minute detail. In our present work, extensive microarray
      analysis in conjunction with PCR validation revealed that there are considerable
      genome dynamics, due to gene acquisition and loss, in natural populations of Y.
      pestis. We established a genomotyping system to group homologous isolates of Y.
      pestis, based on profiling or gene acquisition and loss in their genomes, and
      then drew an outline of parallel microevolution of the Y. pestis genome. The
      acquisition of a number of genomic islands and plasmids most likely induced Y.
      pestis to evolve rapidly from Yersinia pseudotuberculosis to a new, deadly
      pathogen. Horizontal gene acquisition also plays a key role in the dramatic
      evolutionary segregation of Y. pestis lineages (biovars and genomovars). In
      contrast to selective genome expansion by gene acquisition, genome reduction
      occurs in Y. pestis through the loss of DNA regions. We also theorized about the
      links between niche adaptation and genome microevolution. The transmission,
      colonization, and expansion of Y. pestis in the natural foci of endemic plague
      are parallel and directional and involve gradual adaptation to the complex of
      interactions between the environment, the hosts, and the pathogen itself. These
      adaptations are based on the natural selections against the accumulation of
      genetic changes within genome. Our data strongly support that the modern plague
      originated from Yunnan Province in China, due to the arising of biovar orientalis
      from biovar antiqua rather than mediaevalis.

PMID- 15262951
TI  - Genetics of metabolic variations between Yersinia pestis biovars and the proposal
      of a new biovar, microtus.
AB  - Yersinia pestis has been historically divided into three biovars: antiqua,
      mediaevalis, and orientalis. On the basis of this study, strains from Microtus
      related plague foci are proposed to constitute a new biovar, microtus. Based on
      the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis
      strains can be assigned to one of four biovars: antiqua (glycerol positive,
      arabinose positive, and nitrate positive), mediaevalis (glycerol positive,
      arabinose positive, and nitrate negative), orientalis (glycerol negative,
      arabinose positive, and nitrate positive), and microtus (glycerol positive,
      arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene
      results in the glycerol-negative characteristic of biovar orientalis strains. Two
      kinds of point mutations in the napA gene may cause the nitrate reduction
      negative characteristic in biovars mediaevalis and microtus, respectively. A 122
      bp frameshift deletion in the araC gene may lead to the arabinose-negative
      phenotype of biovar microtus strains. Biovar microtus strains have a unique
      genomic profile of gene loss and pseudogene distribution, which most likely
      accounts for the human attenuation of this new biovar. Focused, hypothesis-based
      investigations on these specific genes will help delineate the determinants that
      enable this deadly pathogen to be virulent to humans and give insight into the
      evolution of Y. pestis and plague pathogenesis. Moreover, there may be the
      implications for development of biovar microtus strains as a potential vaccine.

PMID- 15262952
TI  - PBP1 is a component of the Bacillus subtilis cell division machinery.
AB  - Bacillus subtilis penicillin-binding protein PBP1 has been implicated in cell
      division. We show here that a PBP1 knockout strain is affected in the formation
      of the asymmetric sporulation septum and that green fluorescent protein-PBP1
      localizes to the sporulation septum. Localization of PBP1 to the vegetative
      septum is dependent on various cell division proteins. This study proves that
      PBP1 forms part of the B. subtilis cell division machinery.

PMID- 15262953
TI  - Cellular levels of trp RNA-binding attenuation protein in Bacillus subtilis.
AB  - Expression of the Bacillus subtilis trp genes is negatively regulated by an 11
      subunit trp RNA-binding attenuation protein (TRAP), which is activated to bind
      RNA by binding l-tryptophan. We used Western blotting to estimate that there are
      200 to 400 TRAP 11-mer molecules per cell in cells grown in either minimal or
      rich medium.

PMID- 15262954
TI  - Expression of a functional secreted YopN-TyeA hybrid protein in Yersinia pestis
      is the result of a +1 translational frameshift event.
AB  - YopN is a secreted protein that prior to secretion directly interacts with the
      cytosolic SycN/YscB chaperone complex and TyeA. This study identifies a secreted
      YopN-TyeA hybrid protein that is expressed by Yersinia pestis, but not by
      Yersinia enterocolitica. DNA sequence analysis and site-directed mutagenesis
      studies demonstrate that the hybrid protein is the result of a +1 translational
      frameshift event.

PMID- 15262955
TI  - The ompU Paralogue vca1008 is required for virulence of Vibrio cholerae.
AB  - We made single and combined mutations in ompU, ompT, and the two putative porin
      genes vca1008 and vc0972. The fitness of the strains was tested in vitro and in
      the infant mouse model of intestinal infection. We also studied the
      transcriptional induction of vca1008 in vitro and during mouse infection. We show
      that vca1008 is induced during infection and is necessary and sufficient (in the
      absence of ompU, ompT, and vc0972) for infection.

PMID- 15262957
TI  - Polyphosphate synthetic activity of polyphosphate:AMP phosphotransferase in
      Acinetobacter johnsonii 210A.
AB  - Polyphosphate:AMP phosphotransferase (PAP) has been identified as an enzyme that
      catalyzes the phosphorylation of AMP with inorganic polyphosphates [poly(P)] as
      phosphate donors. We found that the purified PAP of Acinetobacter johnsonii 210A
      has poly(P) synthetic activity. The PAP catalyzes the dephosphorylation of ADP
      and processively synthesizes poly(P) of 200 to 700 residues. Comparatively lower
      concentrations of MgCl(2) (20 mM) were required to obtain optimum poly(P)
      synthetic activity, whereas higher concentrations of MgCl(2) (100 mM) were
      necessary for optimum PAP activity. ADP is preferred over GDP as a phosphate
      donor for poly(P) synthesis. The K(m) and V(max) values for ADP in the poly(P)
      synthetic activity of PAP were 8.3 mM and 55 micromol min(-1) mg(-1),
      respectively. We concluded that the PAP of A. johnsonii 210A is a novel type of
      poly(P) kinase that uses ADP and GDP as substrates.

PMID- 15262956
TI  - Biochemical study of multiple CheY response regulators of the chemotactic pathway
      of Rhodobacter sphaeroides.
AB  - The six copies of the response regulator CheY from Rhodobacter sphaeroides bind
      to the switch protein FliM. Phosphorylation by acetyl phosphate (AcP) was
      detected by tryptophan fluorescence quenching in three of the four CheYs that
      contain this residue. Autophosphorylation with Ac(32)P was observed in five CheY
      proteins. We also show that all of the cheY genes are expressed simultaneously;
      therefore, in vivo all of the CheY proteins could bind to FliM to control the
      chemotactic response. Consequently, we hypothesize that in this complex
      chemotactic system, the binding of some CheY proteins to FliM, does not
      necessarily imply switching of the flagellar motor.

PMID- 15262958
TI  - Evolution of the Helicobacter pylori vacuolating cytotoxin in a human stomach.
AB  - We describe two subclones of Helicobacter pylori, isolated contemporaneously from
      a human stomach, which differ markedly in the vacuolating cytotoxin gene, vacA,
      but whose near identity in sequences outside this locus implies a very recent
      common origin. The differences are consistent with homologous recombination with
      DNA from another strain and result in a changed vacA midregion and, importantly,
      in changed toxicity.

PMID- 15262959
TI  - Novel sensors of the regulatory switch on the regulatory light chain of smooth
      muscle Myosin.
AB  - Smooth muscle myosin can be switched on by phosphorylation of Ser-19 of the
      regulatory light chain. Our previous photocross-linking results suggested that an
      element of the structural mechanism for the regulatory switch was a
      phosphorylation-induced motion of the regulatory light chain N terminus
      (Wahlstrom, J. L., Randall, M. A., Jr., Lawson, J. D., Lyons, D. E., Siems, W.
      F., Crouch, G. J., Barr, R., Facemyer, K. C., and Cremo, C. R. (2003) J. Biol.
      Chem. 278, 5123-5131). Here we used three different approaches to test this
      notion, which are reactivity of cysteine thiols, pyrene and acrylodan spectral
      analysis, and pyrene fluorescence quenching. All methods detected significant
      differences between the unphosphorylated and phosphorylated regulatory light
      chain N termini in heavy meromyosin, a double-headed subfragment with an intact
      regulatory switch. These differences were not observed for subfragment-1, a
      single-headed, unregulated subfragment. In the presence of either ATP or ADP,
      phosphorylation increased the solvent exposure and decreased the polarity of the
      environment about position 23 of the regulatory light chain of heavy meromyosin.
      These phosphorylation-induced structural changes were not as evident in the
      absence of nucleotides. Nucleotide binding to unphosphorylated heavy meromyosin
      caused a decrease in exposure and an increase in polarity of the N terminus,
      whereas the effects of nucleotide on phosphorylated heavy meromyosin were the
      opposite. We showed a direct correlation between the kinetics of nucleotide
      binding/turnover and the conformational change reported by acrylodan at position
      23 of the regulatory light chain. Acrylodan-A23C also reports the heads up
      (extended) to flexed (folded) transition in unphosphorylated heavy meromyosin.
      This is the first demonstration of direct coupling of nucleotide binding to
      conformational changes in the N terminus of the regulatory light chain.

PMID- 15262960
TI  - The Fanconi anemia gene product FANCF is a flexible adaptor protein.
AB  - The Fanconi anemia (FA) protein FANCF is an essential component of a nuclear core
      complex that protects the genome against chromosomal instability, but the
      specific function of FANCF is still poorly understood. Based upon the homology
      between human and Xenopus laevis FANCF, we carried out an extensive mutagenesis
      study to examine which domains are functionally important and to gain more
      insight into the function of FANCF. In contrast to previous suggestions, we show
      that FANCF does not have a ROM-like function. We found that the C terminus of
      FANCF interacts directly with FANCG and allows the assembly of other FA proteins
      into a stable complex. The N terminus appears to stabilize the interaction with
      FANCA and FANCG and is essential for the binding of the FANCC/FANCE subcomplex.
      We identified several important amino acids in this N-terminal region but,
      surprisingly, many amino acid changes failed to affect the function of the FANCF
      protein. Our data demonstrate that FANCF acts as a flexible adaptor protein that
      plays a key role in the proper assembly of the FA core complex.

PMID- 15262961
TI  - Tobacco smoke control of mucin production in lung cells requires oxygen radicals
      AP-1 and JNK.
AB  - In smokers' lungs, excessive mucus clogs small airways, impairing respiration and
      promoting recurrent infection. A breakthrough in understanding this pathology was
      the realization that smoke could directly stimulate mucin synthesis in lung
      epithelial cells and that this phenomenon was dependent on the cell surface
      receptor for epidermal growth factor, EGFR. Distal steps in the smoke-triggered
      pathway have not yet been determined. We report here that the predominant airway
      mucin (MUC5AC) undergoes transcriptional up-regulation in response to tobacco
      smoke; this is mediated by an AP-1-containing response element, which binds JunD
      and Fra-2. These transcription factors require phosphorylation by upstream
      kinases JNK and ERK, respectively. Whereas ERK activation results from the
      upstream activation of EGFR, JNK activation is chiefly EGFR-independent. Our
      experiments demonstrated that smoke activates JNK via a Src-dependent, EGFR
      independent signaling cascade initiated by smoke-induced reactive oxygen species.
      Taken together with our earlier results, these data indicate that the induction
      of mucin by smoke is the combined effect of mutually independent, reactive oxygen
      species activation of both EGFR and JNK.

PMID- 15262962
TI  - Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent
      protein kinase.
AB  - Full activation of protein kinase B (PKB)/Akt requires phosphorylation on Thr-308
      and Ser-473 by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 kinase
      (S473K), respectively. Although PDK1 has been well characterized, the
      identification of the S473K remains controversial. A major PKB Ser-473 kinase
      activity was purified from the membrane fraction of HEK293 cells and found to be
      DNA-dependent protein kinase (DNA-PK). DNA-PK co-localized and associated with
      PKB at the plasma membrane. In vitro, DNA-PK phosphorylated PKB on Ser-473,
      resulting in a approximately 10-fold enhancement of PKB activity. Knockdown of
      DNA-PK by small interfering RNA inhibited Ser-473 phosphorylation induced by
      insulin and pervanadate. DNA-PK-deficient glioblastoma cells did not respond to
      insulin at the level of Ser-473 phosphorylation; this effect was restored by
      complementation with the human PRKDC gene. We conclude that DNA-PK is a long
      sought after kinase responsible for the Ser-473 phosphorylation step in the
      activation of PKB.

PMID- 15262963
TI  - Closely related mammals have distinct asialoglycoprotein receptor carbohydrate
      specificities.
AB  - We recently reported that the rat asialoglycoprotein receptor binds
      oligosaccharides terminating with sialic acid (Sia) alpha2,6GalNAc. Despite a
      high percentage of identical amino acids in their sequences, orthologues of the
      asialoglycoprotein receptor (ASGP-R) in different mammals differ in their
      specificity for terminal Siaalpha2,6GalNAc. The recombinant subunit 1 of the ASGP
      R from the rat (RHL-1 or rat hepatic lectin) and the mouse (MHL-1 or mouse
      hepatic lectin), which differ at only 12 positions in the amino acid sequence of
      their carbohydrate recognition domains, binds
      Siaalpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man-bovine serum albumin and
      GalNAcbeta1,4GlcNAcbeta1,2Man-bovine serum albumin in ratios of 16:1.0 and
      1.0:1.0, respectively. Mutagenesis was used to show that amino acids both in the
      immediate vicinity of the proposed binding site for terminal GalNAc and on the
      alpha2 helix that is distant from the binding site contribute to the specificity
      for terminal Siaalpha2,6GalNAc. Thus, multiple amino acid sequence alterations in
      two key locations contribute to the difference in specificity observed for the
      rat and mouse ASGP-Rs. We hypothesize that the altered specificity of ASPG-R
      orthologues in such evolutionarily closely related species reflects rapidly
      changing requirements for recognition of endogenous or exogenous oligosaccharides
      in vivo.

PMID- 15262965
TI  - Inhibitors of the quinone-binding site allow rapid superoxide production from
      mitochondrial NADH:ubiquinone oxidoreductase (complex I).
AB  - Neither the route of electron transport nor the sites or mechanism of superoxide
      production in mitochondrial complex I has been established. We examined the rates
      of superoxide generation (measured as hydrogen peroxide production) by rat
      skeletal muscle mitochondria under a variety of conditions. The rate of
      superoxide production by complex I during NADH-linked forward electron transport
      was less than 10% of that during succinate-linked reverse electron transport even
      when complex I was fully reduced by pyruvate plus malate in the presence of the
      complex III inhibitor, stigmatellin. This asymmetry was not explained by
      differences in protonmotive force or its components. However, when inhibitors of
      the quinone-binding site of complex I were added in the presence of ATP to
      generate a pH gradient, there was a rapid rate of superoxide production by
      forward electron transport that was as great as the rate seen with reverse
      electron transport at the same pH gradient. These observations suggest that
      quinone-binding site inhibitors can make complex I adopt the highly radical
      producing state that occurs during reverse electron transport. Despite complete
      inhibition of NADH: ubiquinone oxidoreductase activity in each case, different
      classes of quinone-binding site inhibitor (rotenone, piericidin, and high
      concentrations of myxothiazol) gave different rates of superoxide production
      during forward electron transport (the rate with myxothiazol was twice that with
      rotenone) suggesting that the site of rapid superoxide generation by complex I is
      in the region of the ubisemiquinone-binding sites and not upstream at the flavin
      or low potential FeS centers.

PMID- 15262964
TI  - Gadd45 proteins induce G2/M arrest and modulate apoptosis in kidney cells exposed
      to hyperosmotic stress.
AB  - Gadd45 proteins are induced by hyperosmolality in renal inner medullary (IM)
      cells, but their role for cell adaptation to osmotic stress is not known. We show
      that a cell line derived from murine renal IM cells responds to moderate
      hyperosmotic stress (540 mosmol/kg) by activation of G(2)/M arrest without
      significant apoptosis. If the severity of hyperosmotic stress exceeds the
      tolerance limit of this cell line (620 mosmol/kg) apoptosis is strongly induced.
      Using transient overexpression of ectopic Gadd45 proteins and simultaneous
      analysis of transfected versus non-transfected cells by laser-scanning cytometry,
      we were able to measure the effects of Gadd45 super-induction during
      hyperosmolality on G(2)/M arrest and apoptosis. Our results demonstrate that
      induction of all three Gadd45 isoforms inhibits mitosis and promotes G(2)/M
      arrest during moderate hyperosmotic stress but not in isosmotic controls.
      Furthermore, all three Gadd45 proteins are also involved in control of apoptosis
      during severe hyperosmotic stress. Under these conditions Gadd45gamma induction
      strongly potentiates apoptosis. In contrast, Gadd45alpha/beta induction
      transiently increases caspase 3/7 and annexin V binding before 12 h but inhibits
      later stages of apoptosis during severe hyperosmolality. These results show that
      Gadd45 isoforms function in common but also in distinct pathways during
      hyperosmolality and that their increased abundance contributes to the low mitotic
      index and protection of genomic integrity in cells of the mammalian renal inner
      medulla.

PMID- 15262966
TI  - Mechanism of the generation of autonomous activity of Ca2+/calmodulin-dependent
      protein kinase IV.
AB  - Ca2+/calmodulin-dependent protein kinase IV (CaM-KIV) is phosphorylated at Thr196
      by Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), resulting in
      induction of both autonomous activity and a high level of Ca2+/CaM-dependent
      activity. We have shown that the kinetics of Thr196 phosphorylation of CaM-KIV by
      CaM-KK is well correlated with the generation of its autonomous activity,
      although Thr177 phosphorylation of CaM-KI does not induce its autonomous
      activity. The activities of CaM-KI chimera mutants fused with C-terminal regions
      (residues 296-469 and 296-350) of CaM-KIV are completely dependent on Ca2+/CaM,
      which is also the case for CaM-KI. Unlike wild-type CaM-KI, however,
      phosphorylation of Thr177 in the chimera mutants by CaM-KK resulted in generation
      of significant autonomous activities, indicating that the phosphorylation of Thr
      in the activation loop is sufficient to partially release the autoinhibitory
      region of CaM-KIV from the catalytic core. Indeed, the CaM-KIV peptide (residues
      304-325) containing minimum autoinhibitory sequences (residues 314-321)
      suppressed the activity of non-phosphorylated CaM-KIV with an IC50 of
      approximately 50 microm, and this suppression was competitive with respect to the
      peptide substrate; however, the CaM-KIV peptide was not capable of inhibiting
      Thr196-phosphorylated CaM-KIV. Taken together, these results indicated that the
      Thr196 phosphorylation of CaM-KIV by CaM-KK reduced the interaction of the
      catalytic core with the autoinhibitory region, resulting in generation of the
      autonomous activity.

PMID- 15262968
TI  - Mechanism of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase, a key
      enzyme in the methanopterin biosynthetic pathway.
AB  - The first committed step in methanopterin biosynthesis is catalyzed by 4-(beta-D
      ribofuranosyl)aminobenzene 5'-phosphate (RFA-P) synthase. Unlike all known
      phosphoribosyltransferases, beta-RFA-P synthase catalyzes the unique formation of
      a C-riboside instead of an N-riboside in the condensation of p-aminobenzoic acid
      (pABA) and 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) to produce 4-(beta-D
      ribofuranosyl)aminobenzene 5'-phosphate (beta-RFA-P), CO(2), and inorganic
      pyrophosphate (PP(i)). Here we report the successful cloning, active
      overexpression in Escherichia coli, and purification of this homodimeric enzyme
      containing two 36.2-kDa subunits from the methanogen Methanococcus jannaschii.
      Steady-state initial velocity and product inhibition kinetic studies indicate an
      ordered Bi-Ter mechanism involving binding of PRPP, then pABA, followed by
      release of the products CO(2), then beta-RFA-P, and finally PP. The Michaelis
      parameters are as follows: K(m)pABA, 0.15 mm; K(m)PRPP, 1.50 mm; V(max), 375
      nmol/min/mg; k(cat), 0.23 s(-1). CO(2) showed uncompetitive inhibition, K(i) =
      0.990 mm, under varied PRPP and saturated pABA, and a mixed type of inhibition,
      K(1) = 1.40 mm and K = 3.800 mm, under varied pABA and saturated PRPP. RFA-P
      showed uncompetitive inhibition, K(i) = 0.210 mm, under varied PRPP and saturated
      pABA, and again uncompetitive, K(i) = 0.300 mm, under saturated PRPP and varied
      pABA. PP(i) exhibits competitive inhibition, K(i) = 0.320 mm, under varied PRPP
      and saturated pABA, and a mixed type of inhibition, K(1) = 0.60 mm and K(2) =
      1.900 mm, under saturated PRPP and varied pABA. Synthase lacks any chromogenic
      cofactor, and the presence of pyridoxal phosphate and the mechanistically related
      pyruvoyl cofactors has been strictly excluded.

PMID- 15262967
TI  - The cytoplasmic membrane-proximal domain of the HtrII transducer interacts with
      the E-F loop of photoactivated Natronomonas pharaonis sensory rhodopsin II.
AB  - The structures of the cytoplasmic loops of the phototaxis receptor sensory
      rhodopsin II (SRII) and the membrane-proximal cytoplasmic domain of its bound
      transducer HtrII were examined in the dark and in the light-activated state by
      fluorescent probes and cysteine cross-linking. Light decreased the accessibility
      of E-F loop position 154 in the SRII-HtrII complex, but not in free SRII,
      consistent with HtrII proximity, which was confirmed by tryptophans placed within
      a 5-residue region identified in the HtrII membrane-proximal domain that
      exhibited Forster resonance energy transfer to a fluorescent probe at position
      154 in SRII. The Forster resonance energy transfer was eliminated in the
      signaling deficient HtrII mutant G83F without loss of affinity for SRII. Finally,
      the presence of SRII and HtrII reciprocally inhibit homodimer disulfide cross
      linking reactions in their membrane-proximal domains, showing that each
      interferes with the others self-interaction in this region. The results
      demonstrate close proximity between SRII-HtrII in the membrane-proximal domain,
      and in addition, light stimulation of the SRII inhibition of HtrII cross-linking
      was observed, indicating that the contact is enhanced in the photoactivated
      complex. A mechanism is proposed in which photoactivation alters the SRII-HtrII
      interaction in the membrane-proximal region during the signal relay process.

PMID- 15262969
TI  - PetC1 is the major Rieske iron-sulfur protein in the cytochrome b6f complex of
      Synechocystis sp. PCC 6803.
AB  - Many of the completely sequenced cyanobacterial genomes contain a gene family
      that encodes for putative Rieske iron-sulfur proteins. The Rieske protein is one
      of the large subunits of the cytochrome bc-type complexes involved in respiratory
      and photosynthetic electron transfer. In contrast to all other subunits of this
      complex that are encoded by single genes, the genome of the cyanobacterium
      Synechocystis PCC 6803 contains three petC genes, all encoding potential Rieske
      subunits. Most interestingly, any of the petC genes can be deleted individually
      without altering the Synechocystis phenotype dramatically. In contrast, double
      deletion experiments revealed that petC1 and petC2 cannot be deleted in
      combination, whereas petC3 can be deleted together with any of the other two petC
      genes. Further results suggest a different physiological function for each of the
      Rieske proteins. Whereas PetC2 can partly replace the dominating Rieske isoform
      PetC1, PetC3 is unable to functionally replace either PetC1 or PetC2 and may have
      a special function involving a special donor with a lower redox potential than
      plastoquinone. A predominant role of PetC1, which is (partly) different from
      PetC2, is suggested by the mutational analysis and a detailed characterization of
      the electron transfer reactions in the mutant strains.

PMID- 15262970
TI  - Spatial contacts and nucleosome step movements induced by the NURF chromatin
      remodeling complex.
AB  - The nucleosome remodeling factor NURF is a four-subunit, ISWI-containing
      chromatin remodeling complex that catalyzes nucleosome sliding in an ATP
      dependent fashion, thereby modulating the accessibility of the DNA. To elucidate
      the mechanism of nucleosome sliding, we have investigated by hydroxyl radical
      footprinting how NURF makes initial contact with a nucleosome positioned at one
      end of a DNA fragment. NURF binds to two separate locations on the nucleosome: a
      continuous stretch of linker DNA up to the nucleosome entry site and a region
      asymmetrically surrounding the nucleosome dyad within the minor grooves, close to
      residues of the histone H4 tail that have been implicated in the activation of
      ISWI activity. Kinetic analysis reveals that nucleosome sliding occurs in
      apparent increments or steps of 10 bp. Furthermore, single nucleoside gaps as
      well as nicks about two helical turns before the dyad interfere with sliding,
      indicating that structural stress at this region assists the relative movement of
      DNA. These findings support a sliding model in which the position-specific
      tethering of NURF forces a translocating ISWI ATPase to pump a DNA distortion
      over the histone octamer, thereby changing the translational position of the
      nucleosome.

PMID- 15262971
TI  - Expression of transglutaminase substrate activity on Candida albicans germ tubes
      through a coiled, disulfide-bonded N-terminal domain of Hwp1 requires C-terminal
      glycosylphosphatidylinositol modification.
AB  - By serving as a microbial substrate for epithelial cell transglutaminase, Hwp1
      (Hyphal wall protein 1) of Candida albicans participates in cross-links with
      proteins on the mammalian mucosa. Biophysical properties of the transglutaminase
      substrate domain were explored using a recombinant protein representative of the
      N-terminal domain of Hwp1 and were similar to other transglutaminase substrates,
      the small proline-rich proteins of cornified envelopes found in stratified
      squamous epithelia. Recombinant Hwp1 lacks alpha and beta structures by circular
      dichroism and likely exists as a disulfide-cross-linked coiled-coil. The
      transglutaminase substrate property prompted a unique approach for investigating
      the features of surface Hwp1 on germ tubes. A lysine analog, 5
      (biotinamido)pentylamine, was cross-linked to germ tubes catalyzed by
      transglutaminase 2 prior to cell fractionation, immunoprecipitation, and
      detection with streptavidin conjugates. The majority of the transglutaminase
      modifiable Hwp1 was covalently attached to the beta-glucan of hyphae by the C
      terminus of Hwp1 via a glycosylphosphatidylinositol remnant anchor. A putative
      precursor of cell wall forms of Hwp1 was identified in the cell extract and in
      the culture medium. Hwp1 was modified by relatively short N-linked glycans, and
      the molecular size of the protein was reduced by hypomannosylation when expressed
      in O-glycosylation mutant strains. Hwp1 combines features of mammalian
      transglutaminase substrate proteins with characteristics of fungal cell wall
      proteins to form an unconventional adhesin at the hyphal wall of C. albicans.

PMID- 15262972
TI  - Discrimination against deoxyribonucleotide substrates by bacterial RNA
      polymerase.
AB  - Nucleic acid polymerases have evolved elaborate mechanisms that prevent
      incorporation of the non-cognate substrates, which are distinguished by both the
      base and the sugar moieties. While the mechanisms of substrate selection have
      been studied in single-subunit DNA and RNA polymerases (DNAPs and RNAPs,
      respectively), the determinants of substrate binding in the multisubunit RNAPs
      are not yet known. Molecular modeling of Thermus thermophilus RNAP-substrate NTP
      complex identified a conserved beta' subunit Asn(737) residue in the active site
      that could play an essential role in selection of the substrate ribose. We
      utilized the Escherichia coli RNAP model system to assess this prediction.
      Functional in vitro analysis demonstrates that the substitutions of the
      corresponding beta' Asn(458) residue lead to the loss of discrimination between
      ribo- and deoxyribonucleotide substrates as well as to defects in RNA chain
      extension. Thus, in contrast to the mechanism utilized by the single-subunit T7
      RNAP where substrate selection commences in the inactive pre-insertion site prior
      to its delivery to the catalytic center, the bacterial RNAPs likely recognize the
      sugar moiety in the active (insertion) site.

PMID- 15262973
TI  - Direct inhibition of type 5 adenylyl cyclase prevents myocardial apoptosis
      without functional deterioration.
AB  - Adenylyl cyclase, a major target enzyme of beta-adrenergic receptor signals, is
      potently and directly inhibited by P-site inhibitors, classic inhibitors of this
      enzyme, when the enzyme catalytic activity is high. Unlike beta-adrenergic
      receptor antagonists, this is a non- or uncompetitive inhibition with respect to
      ATP. We have examined whether we can utilize this enzymatic property to regulate
      the effects of beta-adrenergic receptor stimulation differentially. After
      screening multiple new and classic compounds, we found that some compounds,
      including 1R,4R-3-(6-aminopurin-9-yl)-cyclopentanecarboxylic acid hydroxyamide,
      potently inhibited type 5 adenylyl cyclase, the major cardiac isoform, but not
      other isoforms. In normal mouse cardiac myocytes, contraction induced by low beta
      adrenergic receptor stimulation was poorly inhibited with this compound, but the
      induction of cardiac myocyte apoptosis by high beta-adrenergic receptor
      stimulation was effectively prevented by type 5 adenylyl cyclase inhibitors. In
      contrast, when cardiac myocytes from type 5 adenylyl cyclase knock-out mice were
      examined, beta-adrenergic stimulation poorly induced apoptosis. Our data suggest
      that the inhibition of beta-adrenergic signaling at the level of the type 5
      adenylyl cyclase isoform by P-site inhibitors may serve as an effective method to
      prevent cardiac myocyte apoptosis induced by excessive beta-adrenergic
      stimulation without deleterious effect on cardiac myocyte contraction.

PMID- 15262974
TI  - Lipid rafts regulate lipopolysaccharide-induced activation of Cdc42 and
      inflammatory functions of the human neutrophil.
AB  - Lipid rafts are cholesterol-rich membrane microdomains that are thought to act as
      coordinated signaling platforms by regulating dynamic, agonist-induced
      translocation of signaling proteins. They have been described to play a role in
      multiple prototypical cascades, among them the lipopolysaccharide pathway, and to
      host multiple signaling proteins, including kinases and low molecular weight G
      proteins. Here we report lipopolysaccharide-induced activation of the Rho family
      GTPase Cdc42, and we show its activation in the human neutrophil to be mediated
      by a p38 mitogen-activated protein kinase-dependent mechanism. Subcellular
      fractionation reveals that lipopolysaccharide induces translocation of Cdc42 to
      lipid rafts, where it and p38 are both found to be activated. By contrast,
      lipopolysaccharide causes translocation of Rac from the polymorphonuclear
      leukocyte (PMN) rafts and does not induce its activation. With the use of methyl
      beta-cyclodextrin, a cholesterol-depleting agent that reversibly disrupts rafts,
      we confirm an important regulatory role for rafts in the activation state of p38
      and Cdc42 and in the Rho GTPase-dependent functions superoxide anion production
      and actin polymerization. Methyl-beta-cyclodextrin induces activation of p38 and
      Cdc42, but not Rac, in the nonstimulated PMN, yet inhibits subsequent
      lipopolysaccharide-induced activation of p38 and Cdc42. In parallel, methyl-beta
      cyclodextrin primes the human PMN for subsequent superoxide release triggered by
      the formylated bacterial tripeptide formyl-Met-Leu-Phe, and induces actin
      polymerization in a subcellular distribution distinct from that induced by
      lipopolysaccharide. In sum, these findings provide evidence for an important
      regulatory role of cholesterol in both transmission of the lipopolysaccharide
      signal and the inflammatory phenotype of the human neutrophil.

PMID- 15262975
TI  - Antiapoptotic protein partners fortilin and MCL1 independently protect cells from
      5-fluorouracil-induced cytotoxicity.
AB  - Fortilin, a potent 172-amino acid antiapoptotic polypeptide (Li, F., Zhang, D.,
      and Fujise, K. (2001) J. Biol. Chem. 276, 47542-47549), binds MCL1, a protein of
      the antiapoptotic Bcl-2 family. The fortilin-MCL1 interaction stabilizes and
      increases the half-life of fortilin but not necessarily of MCL1 (Zhang, D., Li,
      F., Weidner, D., Mnjoyan, Z. H., and Fujise, K. (2002) J. Biol. Chem. 277, 37430
      37438). It is not known to what extent each protein depends on the other for its
      apoptotic activity. Here, we present evidence that fortilin and MCL1 are capable
      of functioning as antiapoptotic proteins independently of each other. Using a
      robust small interfering RNA (siRNA)-mediated gene silencing system developed in
      our laboratory, we analyzed the cytoprotective effects of fortilin and MCL1
      together and apart in U2OS cell lines exposed to 5-fluorouracil (5-FU) in both
      monoclonal and polyclonal cell populations. When MCL1 was silenced by MCL1
      targeted siRNA, fortilin was still able to protect cells from 5-FU-induced
      cytotoxicity in a dose-dependent manner. Conversely, when fortilin was silenced
      by fortilin-targeted siRNA, MCL1 was also able to protect cells from 5-FU-induced
      cytotoxicity in a dose-dependent manner. Together, these data clearly suggest
      that fortilin and MCL1 can exert their cytoprotective activities independently of
      each other. The silencing of fortilin and MCL1 did not qualitatively change the
      subcellular localization of MCL1 and fortilin, respectively. The biological
      significance of fortilin-MCL1 interaction may be that it increases cellular
      resistance to apoptosis by allowing MCL1, an independently antiapoptotic protein,
      to stabilize another independently antiapoptotic protein, fortilin.

PMID- 15262976
TI  - Mutations in the R2 subunit of ribonucleotide reductase that confer resistance to
      hydroxyurea.
AB  - Ribonucleotide reductase is an essential enzyme that catalyzes the reduction of
      ribonucleotides to deoxyribonucleotides for use in DNA synthesis. Ribonucleotide
      reductase from Escherichia coli consists of two subunits, R1 and R2. The R2
      subunit contains an unusually stable radical at tyrosine 122 that participates in
      catalysis. Buried deep within a hydrophobic pocket, the radical is inaccessible
      to solvent although subject to inactivation by radical scavengers. One such
      scavenger, hydroxyurea, is a highly specific inhibitor of ribonucleotide
      reductase and therefore of DNA synthesis; thus it is an important anticancer and
      antiviral agent. The mechanism of radical access remains to be established;
      however, small molecules may be able to access Tyr-122 directly via channels from
      the surface of the protein. We used random oligonucleotide mutagenesis to create
      a library of 200,000 R2 mutants containing random substitutions at five
      contiguous residues (Ile-74, Ser-75, Asn-76, Leu-77, Lys-78) that partially
      comprise one side of a channel where Tyr-122 is visible from the protein surface.
      We subjected this library to increasing concentrations of hydroxyurea and
      identified mutants that enhance survival more than 1000-fold over wild-type R2 at
      high drug concentrations. Repetitive selections yielded S75T as the predominant
      R2 mutant in our library. Purified S75TR2 exhibits a radical half-life that is
      50% greater than wild-type R2 in the presence of hydroxyurea. These data
      represent the first demonstration of R2 protein mutants in E. coli that are
      highly resistant to hydroxyurea; elucidation of their mechanism of resistance may
      provide valuable insight into the development of more effective inhibitors.

PMID- 15262977
TI  - The modulation in subunits e and g amounts of yeast ATP synthase modifies
      mitochondrial cristae morphology.
AB  - Subunits e and g of Saccharomyces cerevisiae ATP synthase are required to
      maintain ATP synthase dimeric forms. Mutants devoid of these subunits display
      anomalous mitochondrial morphologies. An expression system regulated by
      doxycycline was used to modulate the expression of the genes encoding the
      subunits e and g. A decrease in the amount of subunit e induces a decrease in the
      amount of subunit g, but a decrease in the amount of subunit g does not affect
      subunit e. The loss of subunit e or g leads to the loss of supramolecular
      structures of ATP synthase, which is fully reversible upon removal of
      doxycycline. In the absence of doxycycline, mitochondria present poorly defined
      cristae. In the presence of doxycycline, onion-like structures are formed after
      five generations. When doxycycline is removed after five generations, cristae are
      mainly observed. The data demonstrate that the inner structure of mitochondria
      depends upon the ability of ATP synthase to make supramolecular structures.

PMID- 15262978
TI  - The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase
      activation by Axin and dishevelled through distinct mechanisms.
AB  - Axin, Ccd1 (coiled-coil-DIX1), and dishevelled (Dvl or Dsh) are three known DIX
      domain proteins that play important roles in Wnt signaling. In addition, Dvl and
      Axin can activate the mitogen-activated protein kinase JNK via distinct
      mechanisms, through interaction with MEKK1/4 and Rac GTPase, respectively. Axin
      utilizes two distinct domains for interaction with MEKK1 and MEKK4. JNK
      activation by Axin is regulated by several factors in the Wnt pathway, whereas
      little is known about cross-regulation of Dvl-mediated JNK activation. In the
      present study, we have investigated whether Ccd1 could play a regulatory role in
      Axin- and Dvl-mediated JNK activation. Here we show that Ccd1 drastically
      inhibited JNK activation both by Axin and by Dvl. Although DIX domains are
      sufficient for dimer formation between Dvl and Ccd1, Ccd1 also required its
      coiled-coil domain for inhibition of JNK activation by Dvl. Interestingly, Rac
      remained associated with Dvl heterodimerized with Ccd1. How Ccd1 blocks Rac/Dvl
      signaling to JNK is unclear. In contrast, Axin, when complexed with Ccd1, did not
      bind to MEKK1. Furthermore, Ccd1 physically interacted with MEKK4 in their
      physiological concentrations and prevented MEKK4 from binding to Axin. Reduction
      of Ccd1 protein by small interfering RNA could elevate JNK signaling as assayed
      with an AP1-dependent transcriptional reporter. We have therefore demonstrated
      that Ccd1 inhibits Axin-mediated JNK activation by simultaneously adopting two
      distinct mechanisms, one through conformational changes that disallow MEKK1
      binding and the other via direct sequestration of MEKK4.

PMID- 15262979
TI  - Sequential caspase-2 and caspase-8 activation upstream of mitochondria during
      ceramideand etoposide-induced apoptosis.
AB  - Recently, caspase-2 was shown to act upstream of mitochondria in stress-induced
      apoptosis. Activation of caspase-8, a key event in death receptor-mediated
      apoptosis, also has been demonstrated in death receptor-independent apoptosis.
      The regulation of these initiator caspases, which trigger the mitochondrial
      apoptotic pathway, is unclear. Here we report a potential regulatory role of
      caspase-2 on caspase-8 during ceramide-induced apoptosis. Our results demonstrate
      the sequential events of initiator caspase-2 and caspase-8 activation, Bid
      cleavage and translocation, and mitochondrial damage followed by downstream
      caspase-9 and -3 activation and cell apoptosis after ceramide induction in T cell
      lines. The expression of truncated Bid (tBid) and the reduction in mitochondrial
      transmembrane potential were blocked by caspase-2 or caspase-8, but not caspase
      3, knockdown using an RNA interference technique. Ceramide-induced caspase-8
      activation, mitochondrial damage, and apoptosis were blocked in caspase-2 short
      interfering RNA-expressing cells. Therefore, caspase-2 acts upstream of caspase-8
      during ceramide-induced mitochondrial apoptosis. Similarly, sequential caspase-2
      and caspase-8 activation upstream of mitochondria was also observed in etoposide
      induced apoptosis. These data suggest sequential initiator caspase-2 and caspase
      8 activation in the mitochondrial apoptotic pathway induced by ceramide or
      etoposide.

PMID- 15262980
TI  - The Lin12-notch repeats of pregnancy-associated plasma protein-A bind calcium and
      determine its proteolytic specificity.
AB  - The Lin12-Notch repeat (LNR) module of about 35 residues is a hallmark of the
      Notch receptor family. Three copies, arranged in tandem, are invariably present
      in the extracellular portion of the Notch receptors. Although their function is
      unknown, genetic and biochemical data indicate that the LNR modules participate
      in the regulation of ligand-induced proteolytic cleavage of the Notch receptor, a
      prerequisite to intramembrane cleavage and Notch signaling. Outside the Notch
      receptor family, the LNR module is present only in the metalloproteinase
      pregnancy-associated plasma protein-A (PAPP-A) and its homologue PAPP-A2, which
      also contain three copies. Curiously, LNR modules 1 and 2 are present within the
      proteolytic domain of PAPP-A/A2, but LNR3 is separated from LNR2 by more than
      1000 amino acids. The growth factor antagonists insulin-like growth factor
      binding protein (IGFBP)-4 and -5 are both substrates of PAPP-A. We provide here
      evidence that the PAPP-A LNR modules function together to determine the
      proteolytic specificity of PAPP-A. Analysis of C-terminally truncated PAPP-A
      mutants followed by the analysis of LNR deletion mutants demonstrated that each
      of the three PAPP-A LNR modules is strictly required for proteolytic activity
      against IGFBP-4 but not for proteolytic activity against IGFBP-5. Individual
      substitution of conserved LNR residues predicted to participate in calcium
      coordination caused elimination (D341A, D356A, D389A, D1484A, D1499A, and D1502A)
      or a significant reduction (D359A and E392A) of IGFBP-4 proteolysis, whereas
      IGFBP-5 proteolysis was unaffected. The activity of the latter mutants against
      IGFBP-4 could be partially rescued by calcium, and the addition of the calcium
      binding protein calbindin D9k to wild-type PAPP-A eliminated activity against
      IGFBP-4 but not against IGFBP-5, demonstrating that the PAPP-A LNR modules bind
      calcium ions. We propose a model in which LNR3 is spatially localized in
      proximity to LNR1 and -2, forming a single functional unit.

PMID- 15262981
TI  - Exon skipping of cathepsin B: mitochondrial targeting of a lysosomal peptidase
      provokes cell death.
AB  - The alternatively spliced messenger RNA of the human cysteine peptidase cathepsin
      B missing exons 2 and 3 encodes a truncated form of the enzyme lacking the signal
      peptide and part of the inhibitory propeptide. This deletion results in a new N
      terminal leader sequence characteristic of proteins predestined for transport
      into mitochondria. We determined enzyme targeting to intracellular organelles by
      transfecting HeLa cells with constructs containing segments of variable length of
      the N terminus of truncated cathepsin B fused to green fluorescent protein. Co
      localization of the constructs with mitochondria and the endoplasmic reticulum
      was probed with specific markers. None of the chimeric products were found in the
      endoplasmic reticulum, showing that truncated cathepsin B is misrouted from its
      regular biosynthetic pathway and forced to enter the mitochondria instead of
      lysosomes as its final destination. The first 20 amino acids of the new N
      terminus were necessary and sufficient for mitochondrial targeting, but only
      cells expressing the complete truncated cathepsin B sequence died by nuclear
      fragmentation. This new and unexpected behavior draws attention to an additional
      extralysosomal role for a cysteine peptidase with several recognized important
      pathophysiological functions. Mitochondrial targeting of cathepsin B may have
      significant consequences on cell life in pathological or physiological situations
      characterized by excessive transcription of the cathepsin B message lacking exons
      2 and 3, as observed for instance in osteoarthritic cartilage.

PMID- 15262982
TI  - RC3/Neurogranin and Ca2+/calmodulin-dependent protein kinase II produce opposing
      effects on the affinity of calmodulin for calcium.
AB  - The interaction of calmodulin with its target proteins is known to affect the
      kinetics and affinity of Ca(2+) binding to calmodulin. Based on thermodynamic
      principles, proteins that bind to Ca(2+)-calmodulin should increase the affinity
      of calmodulin for Ca(2+), while proteins that bind to apo-calmodulin should
      decrease its affinity for Ca(2+). We quantified the effects on Ca(2+)-calmodulin
      interaction of two neuronal calmodulin targets: RC3, which binds both Ca(2+)- and
      apo-calmodulin, and alphaCaM kinase II, which binds selectively to Ca(2+)
      calmodulin. RC3 was found to decrease the affinity of calmodulin for Ca(2+),
      whereas CaM kinase II increases the calmodulin affinity for Ca(2+). Specifically,
      RC3 increases the rate of Ca(2+) dissociation from the C-terminal sites of
      calmodulin up to 60-fold while having little effect on the rate of Ca(2+)
      association. Conversely, CaM kinase II decreases the rates of dissociation of
      Ca(2+) from both lobes of calmodulin and autophosphorylation of CaM kinase II at
      Thr(286) induces a further decrease in the rates of Ca(2+) dissociation. RC3
      dampens the effects of CaM kinase II on Ca(2+) dissociation by increasing the
      rate of dissociation from the C-terminal lobe of calmodulin when in the presence
      of CaM kinase II. This effect is not seen with phosphorylated CaM kinase II. The
      results are interpreted according to a kinetic scheme in which there are
      competing pathways for dissociation of the Ca(2+)-calmodulin target complex. This
      work indicates that the Ca(2+) binding properties of calmodulin are highly
      regulated and reveals a role for RC3 in accelerating the dissociation of Ca(2+)
      calmodulin target complexes at the end of a Ca(2+) signal.

PMID- 15262983
TI  - Inhibition of JNK2 disrupts anaphase and produces aneuploidy in mammalian cells.
AB  - The JNK family members JNK1 and JNK2 regulate tumor growth and are essential for
      transformation by oncogenes such as constitutively activated Ras. The mechanisms
      downstream of JNK that regulate cell cycle progression and transformation are
      unclear. Here we show that inhibition of JNK2, but not JNK1, with either a
      dominant-negative mutant, a pharmacological inhibitor, or RNA interference caused
      an accumulation of mammalian cells with 4N DNA content. When observed by
      immunofluorescence, these cells progressed to metaphase without apparent defects
      in spindle formation or chromosome alignment to the metaphase plate, suggesting
      that the 4N accumulation is a result of postmetaphase defects. Consistent with
      this prediction, when JNK activity was suppressed, we observed defects in central
      spindle formation and chromosome segregation during anaphase. In contrast, cyclin
      dependent kinase 1 activity, cyclin B1 protein, and Polo-like kinase 1 protein
      turnover remained intact when JNK was inhibited. In addition, continued
      inhibition of JNK activity did not block reentry into subsequent cell cycles but
      instead resulted in polyploidy. This evidence suggests that JNK2 functions in
      maintaining the genomic stability of mammalian cells by signaling that is
      independent of cyclin-dependent kinase 1/cyclin B1 down-regulation.

PMID- 15262984
TI  - Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene
      expression in embryonic and neural stem cells.
AB  - The Sox2 transcription factor is expressed early in the stem cells of the
      blastocyst inner cell mass and, later, in neural stem cells. We previously
      identified a Sox2 5'-regulatory region directing transgene expression to the
      inner cell mass and, later, to neural stem cells and precursors of the forebrain.
      Here, we identify a core enhancer element able to specify transgene expression in
      forebrain neural precursors of mouse embryos, and we show that the same core
      element efficiently activates transcription in inner cell mass-derived embryonic
      stem (ES) cells. Mutation of POU factor binding sites, able to recognize the
      neural factors Brn1 and Brn2, shows that these sites contribute to transgene
      activity in neural cells. The same sites are also essential for activity in ES
      cells, where they bind different members of the POU family, including Oct4, as
      shown by gel shift assays and chromatin immunoprecipitation with anti-Oct4
      antibodies. Our findings indicate a role for the same POU binding motifs in Sox2
      transgene regulation in both ES and neural precursor cells. Oct4 might play a
      role in the regulation of Sox2 in ES (inner cell mass) cells and, possibly, at
      the transition between inner cell mass and neural cells, before recruitment of
      neural POU factors such as Brn1 and Brn2.

PMID- 15262985
TI  - Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting
      protein.
AB  - We describe the isolation and characterization of a new apaf-1-interacting
      protein (APIP) as a negative regulator of ischemic injury. APIP is highly
      expressed in skeletal muscle and heart and binds to the CARD of Apaf-1 in
      competition with caspase-9. Exogenous APIP inhibits cytochrome c-induced
      activation of caspase-3 and caspase-9, and suppresses cell death triggered by
      mitochondrial apoptotic stimuli through inhibiting the downstream activity of
      cytochrome c released from mitochondria. Conversely, reduction of APIP expression
      potentiates mitochondrial apoptosis. APIP expression is highly induced in mouse
      muscle affected by ischemia produced by interruption of the artery in the
      hindlimb and in C2C12 myotubes created by hypoxia in vitro, and the blockade of
      APIP up-regulation results in TUNEL-positive ischemic damage. Furthermore, forced
      expression of APIP suppresses ischemia/hypoxia-induced death of skeletal muscle
      cells. Taken together, these results suggest that APIP functions to inhibit
      muscle ischemic damage by binding to Apaf-1 in the Apaf-1/caspase-9 apoptosis
      pathway.

PMID- 15262986
TI  - Regulation of Bax activation and apoptotic response to microtubule-damaging
      agents by p53 transcription-dependent and -independent pathways.
AB  - Microtubule-damaging agents (MDA) are potent antineoplastic drugs that are widely
      used in clinical treatment for a variety of cancers. However, the precise
      mechanisms underlying MDA-induced cell death are largely unknown. Here, we report
      that both p53 and Bax are central participants in the MDA-mediated cell death
      machinery in HCT116 human colon cancer cells. MDA, including epothilone B
      analogue (BMS-247550) and vinblastine, induced apoptosis of Bax-positive HCT116
      cells in a p53-dependent manner; p53 was required for MDA-induced Bax
      conformational change. In response to MDA treatment, the BH3-only proapoptotic
      protein PUMA was up-regulated in p53-positive but not in p53 knockout HCT116
      cells. Moreover, PUMA knockout HCT116 cells were resistant to MDA-induced Bax
      conformational change and apoptosis. In addition, introducing p53 plasmid DNA
      into p53-deficient HCT116 cells restored PUMA expression and apoptotic response
      to MDA treatment. However, ectopic expression of the p53 point mutation
      L22Q/W23S, but not the proline-rich domain deletion mutants 83-393 and
      DeltaProAE, could also sensitize p53 knockout HCT116 cells to MDA-induced Bax
      activation and apoptosis, although all mutants failed to restore PUMA expression.
      Together, these findings suggest that p53 acts upstream of Bax to promote MDA
      mediated cell death in a proline-rich domain-dependent manner through both
      transcription-dependent (by up-regulating PUMA expression) and -independent
      mechanisms in human colon cancer HCT116 cells.

PMID- 15262987
TI  - Depolarization of skeletal muscle cells induces phosphorylation of cAMP response
      element binding protein via calcium and protein kinase Calpha.
AB  - Membrane depolarization of skeletal muscle cells induces slow inositol
      trisphosphate-mediated calcium signals that regulate the activity of
      transcription factors such as the cAMP-response element-binding protein (CREB),
      jun, and fos. Here we investigated whether such signals regulate CREB
      phosphorylation via protein kinase C (PKC)-dependent pathways. Western blot
      analysis revealed the presence of seven isoforms (PKCalpha, -betaI, -betaII, 
      delta, -epsilon, -, and -zeta) in rat primary myotubes. The PKC inhibitors
      bisindolymaleimide I and Go6976, blocked CREB phosphorylation. Chronic exposure
      to phorbol ester triggered complete down-regulation of several isoforms, but
      reduced PKCalpha levels to only 40%, and did not prevent CREB phosphorylation
      upon myotube depolarization. Immunocytochemical analysis revealed selective and
      rapid PKCalpha translocation to the nucleus following depolarization, which was
      blocked by 2-amino-ethoxydiphenyl borate, an inositol trisphosphate receptor
      inhibitor, and by the phospholipase C inhibitor U73122. In C2C12 cells, which
      expressed PKCalpha,-epsilon, and -zeta, CREB phosphorylation also depended on
      PKCalpha. These results strongly implicate nuclear PKCalpha translocation in CREB
      phosphorylation induced by skeletal muscle membrane depolarization.

PMID- 15262989
TI  - Dynamin GTPase domain mutants that differentially affect GTP binding, GTP
      hydrolysis, and clathrin-mediated endocytosis.
AB  - The GTPase dynamin is essential for clathrin-mediated endocytosis. Unlike most
      GTPases, dynamin has a low affinity for nucleotide, a high rate of GTP
      hydrolysis, and can self-assemble, forming higher order structures such as rings
      and spirals that exhibit up to 100-fold stimulated GTPase activity. The role(s)
      of GTP binding and/or hydrolysis in endocytosis remain unclear because mutations
      in the GTPase domain so far studied impair both. We generated a new series of
      GTPase domain mutants to probe the mechanism of GTP hydrolysis and to further
      test the role of GTP binding and/or hydrolysis in endocytosis. Each of the
      mutations had parallel effects on assembly-stimulated and basal GTPase
      activities. In contrast to previous reports, we find that mutation of Thr-65 to
      Ala (or Asp or His) dramatically lowered both the rate of assembly-stimulated GTP
      hydrolysis and the affinity for GTP. The assemblystimulated rate of hydrolysis
      was lowered by the mutation of Ser-61 to Asp and increased by the mutation of Thr
      141 to Ala without significantly altering the Km for GTP. For some mutants and to
      a lesser extent for WT dynamin, self-assembly dramatically altered the Km for
      GTP, suggesting that conformational changes in the active site accompany self
      assembly. Analysis of transferrin endocytosis rates in cells overexpressing
      mutant dynamins revealed a stronger correlation with both the basal and assembly
      stimulated rates of GTP hydrolysis than with the calculated ratio of dynamin
      GTP/free dynamin, suggesting that GTP binding is not sufficient, and GTP
      hydrolysis is required for clathrin-mediated endocytosis in vivo.

PMID- 15262988
TI  - Crystal structure of leucotoxin S component: new insight into the Staphylococcal
      beta-barrel pore-forming toxins.
AB  - Staphylococcal leucocidins and gamma-hemolysins (leucotoxins) are bi-component
      toxins that form lytic transmembrane pores. Their cytotoxic activities require
      the synergistic association of a class S component and a class F component,
      produced as water-soluble monomers that form hetero-oligomeric membrane
      associated complexes. Strains that produce the Panton-Valentine leucocidin are
      clinically associated with cutaneous lesions and community-acquired pneumonia. In
      a previous study, we determined the crystal structure of the F monomer from the
      Panton-Valentine leucocidin. To derive information on the second component of the
      leucotoxins, the x-ray structure of the S protein from the Panton-Valentine
      leucocidin was solved to 2.0 angstrom resolution using a tetragonal crystal form
      that contains eight molecules in the asymmetric unit. The structure demonstrates
      the different conformation of the domain involved in membrane contacts and
      illustrates sequence and tertiary structure variabilities of the pore-forming
      leucotoxins. Mutagenesis studies at a key surface residue (Thr-28) further
      support the important role played by these microheterogeneities for the assembly
      of the bipartite leucotoxins.

PMID- 15262990
TI  - CLIPR-59 is a lipid raft-associated protein containing a cytoskeleton-associated
      protein glycine-rich domain (CAP-Gly) that perturbs microtubule dynamics.
AB  - We recently have identified a new cytoplasmic linker protein (CLIP), CLIPR-59,
      which is involved in the regulation of early endosome/trans-Golgi network
      dynamics. In contrast with CLIP-170, CLIPR-59 is not localized to microtubules at
      steady state but is associated with the trans-Golgi network and the plasma
      membrane. Here we show that the last 30 amino acids (C30) are sufficient for
      membrane targeting and that two cysteines in the C30 domain are palmitoylated. We
      demonstrate that CLIPR-59 is associated with lipid rafts via its C-terminal
      palmitoylated domain. In vitro experiments suggest that CLIPR-59 and its
      microtubule-binding domain alone have a better affinity for unpolymerized tubulin
      or small oligomers than for microtubules. In contrast with the CLIP-170
      microtubule-binding domain, the CLIPR-59 microtubule-binding domain diminishes
      microtubule regrowth after nocodazole washout in vivo, showing that this domain
      can prevent microtubule polymerization. In contrast with the role of linker
      between membranes and microtubules that was proposed for CLIP function, CLIPR-59
      thus may have an "anti-CLIP" function by preventing microtubule-raft
      interactions.

PMID- 15262991
TI  - Ankyrin-B targets beta2-spectrin to an intracellular compartment in neonatal
      cardiomyocytes.
AB  - Ankyrin-B is a spectrin-binding protein that is required for localization of
      inositol 1,4,5-trisphosphate receptor and ryanodine receptor in neonatal
      cardiomyocytes. This work addresses the interaction between ankyrin-B and beta(2)
      spectrin in these cells. Ankyrin-B and beta(2)-spectrin are colocalized in an
      intracellular striated compartment overlying the M-line and distinct from T
      tubules, sarcoplasmic reticulum, Golgi, endoplasmic reticulum, lysosomes, and
      endosomes. Beta(2)-Spectrin is absent in ankyrin-B-null cardiomyocytes and is
      restored to a normal striated pattern by rescue with green fluorescent protein
      220-kDa ankyrin-B. We identified two mutants (A1000P and DAR976AAA) located in
      the ZU5 domain which eliminate spectrin binding activity of ankyrin-B. Ankyrin-B
      mutants lacking spectrin binding activity are normally targeted but do not
      reestablish beta(2)-spectrin in ankyrin-B(+/-) cardiomyocytes. However, both
      mutant forms of ankyrin-B are still capable of restoring inositol 1,4,5
      trisphosphate receptor localization and normal contraction frequency of
      cardiomyocytes. Therefore, direct binding of beta(2)-spectrin to ankyrin-B is
      required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes.
      In contrast, ankyrin-B localization and function are independent of beta(2)
      spectrin. In summary, this work demonstrates that interaction between members of
      the ankyrin and beta-spectrin families previously established in erythrocytes and
      axon initial segments also occurs in neonatal cardiomyocytes with ankyrin-B and
      beta(2)-spectrin. This work also establishes a functional hierarchy in which
      ankyrin-B determines the localization of beta(2)-spectrin and operates
      independently of beta(2)-spectrin in its role in organizing membrane-spanning
      proteins.

PMID- 15262992
TI  - Regulation of amphiphysin1 by mitogen-activated protein kinase: its significance
      in nerve growth factor receptor-mediated endocytosis.
AB  - Amphiphysin1, which can simultaneously bind to dynamin1 and the clathrin adaptor
      AP-2, is essential for dynamin1 recruitment during receptor-mediated endocytosis,
      but little is known about its regulatory mechanism. Here, we purified a 120-kDa
      mitogen-activated protein kinase (MAPK) substrate protein from porcine brains and
      identified the protein as amphiphysin1. Serine phosphorylation of amphiphysin1
      was rapidly induced by nerve growth factor (NGF) in PC12 cells, and the induction
      was blocked by a MAPK inhibitor. Furthermore, when phosphorylated by MAPK in
      vitro or by NGF treatment in vivo, amphiphysin1 failed to bind to AP-2, but its
      association with dynamin1 was unaffected. Consistent with this, mutation of
      consensus MAPK phosphorylation sites increased amphiphysin1 binding to AP-2 and
      their intracellular colocalization. Thus, we propose that MAPK phosphorylation of
      amphiphysin1 controls NGF receptor/TrkA-mediated endocytosis by terminating the
      amphiphysin1-AP-2 interaction. This perhaps helps to regulate the availability of
      amphiphysin1-dynamin1 complexes for binding to the endocytic vesicle.

PMID- 15262993
TI  - Role of the p66Shc isoform in insulin-like growth factor I receptor signaling
      through MEK/Erk and regulation of actin cytoskeleton in rat myoblasts.
AB  - To investigate the role of Shc in IGF action and signaling in skeletal muscle
      cells, Shc protein levels were reduced in rat L6 myoblasts by stably
      overexpressing a Shc cDNA fragment in antisense orientation (L6/Shcas). L6/Shcas
      myoblasts showed marked reduction of the p66Shc protein isoform and no change in
      p52Shc or p46Shc proteins compared with control myoblasts transfected with the
      empty vector (L6/Neo). When compared with control, L6/Shcas myoblasts
      demonstrated 3-fold increase in Erk-1/2 phosphorylation under basal conditions
      and blunted Erk-1/2 stimulation by insulin-like growth factor I (IGF-I), in the
      absence of changes in total Erk-1/2 protein levels. Increased basal Erk-1/2
      activation was paralleled by a greater proportion of phosphorylated Erk-1/2 in
      the nucleus of L6/Shcas myoblasts in the absence of IGF-I stimulation. The
      reduction of p66Shc in L6/Shcas myoblasts resulted in marked phenotypic
      abnormalities, such as rounded cell shape and clustering in islets or finger-like
      structures, and was associated with impaired DNA synthesis in response to IGF-I
      and lack of terminal differentiation into myotubes. In addition, L6/Shcas
      myoblasts were characterized by complete disruption of actin filaments and cell
      cytoskeleton. Treatment of L6/Shcas myoblasts with the MEK inhibitor PD98059
      reduced the abnormal increase in Erk-1/2 activation to control levels and
      restored the actin cytoskeleton, re-establishing the normal cell morphology.
      Thus, the p66Shc isoform exerts an inhibitory effect on the mitogen-activated
      protein kinase signaling pathway in rodent myoblasts, which is necessary for
      maintenance of IGF responsiveness of the MEK/Erk pathway and normal cell
      phenotype.

PMID- 15262994
TI  - Calcineurin and calcium/calmodulin-dependent protein kinase activate distinct
      metabolic gene regulatory programs in cardiac muscle.
AB  - To learn more about the targets of Cn (Cn) and calcium/calmodulin-dependent
      protein kinase in cardiac muscle, we investigated their actions in cultured
      cardiac myocytes and the hearts of mice in vivo. Adenoviral-mediated expression
      of constitutively active forms of either pathway induced expression of peroxisome
      proliferator-activated receptor gamma coactivator 1alpha, a transcriptional
      coactivator involved in the control of multiple cellular energy metabolic
      pathways in cardiac myocytes. Transcriptional profiling studies demonstrated that
      Cn and calcium/calmodulin-dependent protein kinase activate distinct but
      overlapping metabolic gene regulatory programs. Expression of the nuclear
      receptor, peroxisome proliferator-activated receptor alpha, was markedly
      increased by Cn, but not calcium/calmodulin-dependent protein kinase, providing
      one mechanism whereby cellular fatty acid utilization genes are selectively
      activated by Cn. Transfection experiments demonstrated that Cn directly activates
      the mouse peroxisome proliferator-activated receptor alpha gene promoter. Co
      transfection "add-back" experiments demonstrated that the transcription factors,
      myocyte enhancer factors 2C or 2D, were sufficient to confer Cn-mediated
      activation of the peroxisome proliferator-activated receptor alpha gene. Cn was
      also shown to directly activate a known peroxisome proliferator-activated
      receptor alpha target, muscle-type carnitine palmitoyltransferase I, providing a
      second mechanism by which Cn activates genes of cellular fatty acid utilization.
      Lastly, the gene expression of peroxisome proliferator-activated receptor gamma
      coactivator 1alpha and peroxisome proliferator-activated receptor alpha was
      reduced in the hearts of mice with cardiac-specific ablation of the Cn regulatory
      subunit. These data support a role for calcium-triggered signaling pathways in
      the regulation of cardiac energetics and identify pathway-specific control of
      metabolic targets.

PMID- 15262995
TI  - H-Ras and phosphoinositide 3-kinase cooperate to induce alpha(1,3)
      fucosyltransferase VII expression in Jurkat T cells.
AB  - The alpha(1,3)-fucosyltransferase FucT-VII is essential for the biosynthesis of
      selectin ligands, but the signaling pathways mediating FucT-VII induction in T
      cells and other lymphocytes are poorly understood. We have shown previously that
      sustained activation of Ras in Jurkat T cells induces FucT-VII transcription,
      which requires the Raf-MEK-ERK pathway. In this study we report that FucT-VII
      induction is specific to the H-Ras isoform. Jurkat T cells retrovirally
      transduced with constitutively active H-Ras but not N- or K-Ras up-regulated
      expression of FucT-VII. Pharmacological inhibition studies also revealed that
      phosphoinositide 3-kinase (PI3K) activity is required for H-Ras-mediated FucT-VII
      induction. However, the ability of H-Ras to selectively induce FucT-VII is not a
      function of the inability of the N- or K-Ras isoforms to activate Raf or PI3K
      pathways. The use of effector-loop domain mutants of H-Ras, which are impaired
      for their ability to interact selectively with individual effectors alone or in
      combination with active Raf, indicated that induction of FucT-VII requires the
      concomitant activation of at least three signaling pathways. These studies show
      that H-Ras mediates FucT-VII induction in Jurkat T cells via the activation of
      the Raf, PI3K, and a distinct, H-Ras-specific effector signaling pathway.

PMID- 15262996
TI  - Fe2+ -catalyzed oxidative cleavages of Ca2+ -ATPase reveal novel features of its
      pumping mechanism.
AB  - We have analyzed the Fe2+ -catalyzed oxidative cleavages of Ca2+ -ATPase in the
      presence of Ca2+, with or without the ATP analog 5'-adenylyl-beta,gamma
      imidodiphosphate (AMP-PNP) or in the presence of the inhibitor thapsigargin. To
      identify the positions of cleavages as precisely as possible, we have used
      previously identified proteinase K and tryptic fragments as a standard, advanced
      mass spectrometry techniques, as well as specific antibodies. A number of
      cleavages are similar to those described for Na+,K+ -ATPase or other P-type pumps
      and are expected on the basis of the putative Mg2+ binding residues near the
      phosphorylated Asp351 in E1 or E2P conformations. However, intriguing new
      features have also been observed. These include a Fe2+ site near M3, which cannot
      be due to the presence of histidine residues as it was postulated in the case of
      Na+,K+ -ATPase and H+,K+ -ATPase. This site could represent a Ca2+ binding zone
      between M1 and M3, preceding Ca2+ occlusion within M4, 5, 6, and 8. In addition,
      we present evidence that, in the non-crystalline state, the N- and P-domain may
      approach each other, at least temporarily, in the presence of Ca2+ (E1Ca2
      conformation), whereas the presence of Mg.ATP stabilizes the N to P interaction
      (E1.Mg.ATP conformation).

PMID- 15262997
TI  - Insulin-like growth factor 1 stimulates KCl cotransport, which is necessary for
      invasion and proliferation of cervical cancer and ovarian cancer cells.
AB  - The mechanisms by which insulin-like growth factor 1 (IGF-1) cooperates with
      membrane ion transport system to modulate epithelial cell motility and
      proliferation remain poorly understood. Here, we investigated the role of
      electroneutral KCl cotransport (KCC), in IGF-1-dependent invasiveness and
      proliferation of cervical and ovarian cancer cells. IGF-1 increased KCC activity
      and mRNA expression in a dose- and time-dependent manner in parallel with the
      enhancement of regulatory volume decrease. IGF-1 treatment triggers
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascades
      leading to the activation of Akt and extracellular signal-regulated kinase1/2
      (Erk1/2), respectively. The activated Erk1/2 mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase signaling pathways are differentially required for
      IGF-1-stimulated biosyn-thesis of KCC polypeptides. Specific reduction of Erk1/2
      protein levels with small interference RNA abolishes IGF-1-stimulated KCC
      activity. Pharmacological inhibition and genetic modification of KCC activity
      demonstrate that KCC is necessary for IGF-1-induced cancer cell invasiveness and
      proliferation. IGF-1 and KCC colocalize in the surgical specimens of cervical
      cancer (n = 28) and ovarian cancer (n = 35), suggesting autocrine or paracrine
      IGF-1 stimulation of KCC production. Taken together, our results indicate that
      KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote
      growth and spread of gynecological cancers.

PMID- 15262998
TI  - Ionic strength and transition metals control PrPSc protease resistance and
      conversion-inducing activity.
AB  - The essential component of infectious prions is a misfolded protein termed PrPSc,
      which is produced by conformational change of a normal host protein, PrPC. It is
      currently unknown whether PrPSc molecules exist in a unique conformation or
      whether they are able to undergo additional conformational changes. Under
      commonly used experimental conditions, PrPSc molecules are characteristically
      protease-resistant and capable of inducing the conversion of PrPC molecules into
      new PrPSc molecules. We describe the effects of ionic strength, copper, and zinc
      on the conformation-dependent protease resistance and conversion-inducing
      activity of PrPSc molecules in scrapie-infected hamster brains. In the absence of
      divalent cations, PrPSc molecules were > 20-fold more sensitive to proteinase K
      digestion in low ionic strength buffers than in high ionic strength buffers.
      Addition of micromolar concentrations of copper or zinc ions restored the
      protease resistance of PrPSc molecules under conditions of low ionic strength.
      These transition metals also controlled the conformation of purified truncated
      PrP-(27-30) molecules at low ionic strength, confirming that the N-terminal
      octapeptide repeat region of PrPSc is not required for binding to copper or zinc
      ions. The protease-sensitive and protease-resistant conformations of PrPSc were
      reversibly interchangeable, and only the protease-resistant conformation of PrPSc
      induced by high ionic strength was able to induce the formation of new protease
      resistant PrP (PrPres) molecules in vitro. These findings show that PrPSc
      molecules are structurally interconvertible and that only a subset of PrPSc
      conformations are able to induce the conversion of other PrP molecules.

PMID- 15262999
TI  - cAMP potentiates ATP-evoked calcium signaling in human parotid acinar cells.
AB  - In salivary acinar cells, intracellular calcium ([Ca(2+)](i)) signaling plays an
      important role in eliciting fluid secretion through the activation of Ca(2+)
      activated ionic conductances. Ca(2+) and cAMP have synergistic effects on fluid
      secretion such that peak secretion is elicited following activation of both
      parasympathetic and sympathetic pathways. We have recently demonstrated that cAMP
      exerts effects on Ca(2+) release, through protein kinase A (PKA)-mediated
      phosphorylation of inositol 1,4,5-trisphosphate receptors (InsP(3)R) in mouse
      parotid acinar cells. To extend these findings, in the present study cross-talk
      between Ca(2+) signaling and cAMP pathways in human parotid acinar cells was
      investigated. In human parotid acinar cells, carbachol stimulation evoked
      increases in the [Ca(2+)](i) and the initial peak amplitude was enhanced
      following PKA activation, consistent with reports from mouse parotid. Stimulation
      with ATP also evoked an increase in [Ca(2+)](i). The ATP-evoked Ca(2+) elevation
      was largely dependent on extracellular Ca(2+), suggesting the involvement of the
      P2X family of purinergic receptors. Pharmacological elevation of cAMP resulted in
      a approximately 5-fold increase in the peak [Ca(2+)](i) change evoked by ATP
      stimulation. This enhanced [Ca(2+)](i) increase was not dependent on
      intracellular release from InsP(3)R or ryanodine receptors, suggesting a direct
      effect on P2XR. Reverse transcription-polymerase chain reaction and Western blot
      analysis confirmed the presence of P2X(4)R and P2X(7)R mRNA and protein in human
      parotid acinar cells. ATP-activated cation currents were studied using whole cell
      patch clamp techniques in HEK-293 cells, a null background for P2XR. Raising cAMP
      resulted in a approximately 4.5-fold enhancement of ATP-activated current in HEK
      293 cells transfected with P2X(4)R DNA but had no effects on currents in cells
      expressing P2X(7)R. These data indicate that in human parotid acinar cells, in
      addition to modulation of Ca(2+) release, Ca(2+) influx through P2X(4)R may
      constitute a further locus for the synergistic effects of Ca(2+) and PKA
      activation.

PMID- 15263000
TI  - The C-terminal domain of aminopeptidase A is an intramolecular chaperone required
      for the correct folding, cell surface expression, and activity of this monozinc
      aminopeptidase.
AB  - Aminopeptidase A (APA, EC 3.4.11.7) is a type II integral membrane glycoprotein
      responsible for the conversion of angiotensin II to angiotensin III in the brain.
      Previous site-directed mutagenesis studies and the recent molecular modeling of
      the APA zinc metallopeptidase domain have shown that all the amino acids involved
      in catalysis are located between residues 200 and 500. The APA ectodomain is
      cleaved in the kidney into an N-terminal fragment corresponding to the zinc
      metallopeptidase domain, and a C-terminal fragment of unknown function. We
      investigated the function of this C-terminal domain, by expressing truncated APAs
      in Chinese hamster ovary and AtT-20 cells. Deletion of the C-terminal domain
      abolished the maturation and enzymatic activity of the N-terminal domain, which
      was retained in the endoplasmic reticulum as an unfolded protein bound to
      calnexin. Expression in trans of the C-terminal domain resulted in association of
      the N- and C-terminal domains soon after biosynthesis, allowing folding rescue,
      maturation, cell surface expression, and activity of the N-terminal zinc
      metallopeptidase domain. We also show that the C-terminal domain is not required
      for the catalytic activity of APA but is essential for its activation. Moreover,
      we show that the C-terminal domain of aminopeptidase N (EC 3.4.11.2, APN) also
      promotes maturation and cell surface expression of the N-terminal domain of APN,
      suggesting a common role of the C-terminal domain in the monozinc aminopeptidase
      family. Our data provide the first demonstration that the C-terminal domain of an
      eukaryotic exopeptidase acts as an intramolecular chaperone.

PMID- 15263001
TI  - Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching
      cells to a cAMP-dependent growth-stimulated phenotype.
AB  - cAMP can be either mitogenic or anti-mitogenic, depending on the cell type. We
      demonstrated previously that cAMP inhibited the proliferation of normal renal
      epithelial cells and stimulated the proliferation of cells derived from the cysts
      of polycystic kidney disease (PKD) patients. The protein products of the genes
      causing PKD, polycystin-1 and polycystin-2, are thought to regulate intracellular
      calcium levels, suggesting that abnormal polycystin function may affect calcium
      signaling and thus cause a switch to the cAMP growth-stimulated phenotype. To
      test this hypothesis, we disrupted intracellular calcium mobilization by treating
      immortalized mouse M-1 collecting duct cells and primary cultures of human kidney
      epithelial cells with calcium channel blockers and by lowering extracellular
      calcium with EGTA. Calcium restriction for 3-5 h converted both cell types from a
      normal cAMP growth-inhibited phenotype to an abnormal cAMP growth-stimulated
      phenotype, characteristic of PKD. In M-1 cells, we showed that calcium
      restriction was associated with an elevation in B-Raf protein levels and cAMP
      stimulated, Ras-dependent activation of B-Raf and ERK. Moreover, the activity of
      Akt, a negative regulator of B-Raf, was decreased by calcium restriction.
      Inhibition of Akt or phosphatidylinositol 3-kinase also allowed cAMP-dependent
      activation of B-Raf and ERK in normal calcium. These results suggest that calcium
      restriction causes an inhibition of the phosphatidylinositol 3-kinase/Akt
      pathway, which relieves the inhibition of B-Raf to allow the cAMP growth
      stimulated phenotypic switch. Finally, M-1 cells stably overexpressing an
      inducible polycystin-1 C-terminal cytosolic tail construct were shown to exhibit
      a cAMP growth-stimulated phenotype involving B-Raf and ERK activation, which was
      reversed by the calcium ionophore A23187. We conclude that disruption of calcium
      mobilization in cells that are normally growth-inhibited by cAMP can derepress
      the B-Raf/ERK pathway, thus converting these cells to a phenotype that is growth
      stimulated by cAMP.

PMID- 15263002
TI  - Truncated structural variants of lipoarabinomannan in Mycobacterium leprae and an
      ethambutol-resistant strain of Mycobacterium tuberculosis.
AB  - Current knowledge on the structure of lipoarabinomannan (LAM) has resulted
      primarily from detailed studies on a few selected laboratory strains of
      Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis.
      Our previous work was the first to report on the salient structural features of
      M. tuberculosis clinical isolates and demonstrated significant structural
      variations. A prime effort is to correlate a particular structural characteristic
      with observed differences in eliciting an immunobiological response, especially
      in the context of CD1-restricted presentation of LAM to T cells. T cell clones
      derived from the cutaneous lesions of leprosy patients have been shown to
      recognize specifically LAM from Mycobacterium leprae and not from M. tuberculosis
      Erdman or H37Rv. Herein we provide further fine structural data on LAM from M.
      leprae (LepLAM) and a tuberculosis clinical isolate, CSU20 (CSU20LAM), which was
      unexpectedly recognized by the supposedly LepLAM-specific CD1-restricted T cell
      clones. In comparison with the de facto laboratory LAM standard from M.
      tuberculosis H37Rv (RvLAM), LepLAM derived from in vivo grown M. leprae is
      apparently simpler in its arabinan architecture with a high degree of exposed,
      non-mannose-capped termini. On the other hand, CSU20, an ethambutol-resistant
      clinical isolate, makes a vastly heterogeneous population of LAM ranging from
      rather small and non-mannose-capped to full-length and fully capped variants.
      LepLAM and CSU20LAM contain a higher level of succinylation than RvLAM, which, in
      the context of truncated or less elaborated arabinan, may contribute to selective
      recognition by T cells. LAM from all species could be resolved into discrete
      forms by isoelectric focusing based apparently on their arabinan heterogeneity.
      In the light of our current and more recent findings, we reason that all
      immunobiological data should be cautiously interpreted and that the actual LAM
      variants that may be present in vivo during infection and pathogenesis need to be
      taken into consideration.

PMID- 15263003
TI  - High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug
      target.
AB  - Rab GTPases and their effectors facilitate vesicular transport by tethering donor
      vesicles to their respective target membranes. Rab9 mediates late endosome to
      trans-Golgi transport and has recently been found to be a key cellular component
      for human immunodeficiency virus-1, Ebola, Marburg, and measles virus
      replication, suggesting that it may be a novel target in the development of broad
      spectrum antiviral drugs. As part of our structure-based drug design program, we
      have determined the crystal structure of a C-terminally truncated human Rab9
      (residues 1-177) to 1.25-A resolution. The overall structure shows a
      characteristic nucleotide binding fold consisting of a six-stranded beta-sheet
      surrounded by five alpha-helices with a tightly bound GDP molecule in the active
      site. Structure-based sequence alignment of Rab9 with other Rab proteins reveals
      that its active site consists of residues highly conserved in the Rab GTPase
      family, implying a common catalytic mechanism. However, Rab9 contains seven
      regions that are significantly different in conformation from other Rab proteins.
      Some of those regions coincide with putative effector-binding sites and switch I
      and switch II regions identified by structure/sequence alignments. The Rab9
      structure at near atomic resolution provides an excellent model for structure
      based antiviral drug design.

PMID- 15263004
TI  - The fourth transmembrane domain of the Helicobacter pylori Na+/H+ antiporter NhaA
      faces a water-filled channel required for ion transport.
AB  - Cysteine-scanning mutagenesis was performed from Ser-130 to Leu-160 in the fourth
      transmembrane domain (TM4) of the Na+/H+ antiporter NhaA from Helicobacter pylori
      to determine the topology of each residue and to identify functionally important
      residues. All of the mutants were based on cysteine-less NhaA (Cys-less NhaA),
      which functions very similarly to the wild-type protein, and were expressed at a
      level similar to Cys-less NhaA. Discontinuity of [14C]N-ethylmaleimide (NEM)
      reactive residues suggested that TM4 comprises residues Gly-135 to Val-156. Even
      within TM4, NEM reactivity was high for I136C, D141C to A143C, L146C, M150C, and
      G153C to R155C. These residues are thought to be located on one side of the 
      helical structure of TM4 and to face a putative water-filled channel.
      Pretreatment of intact cells with membrane-impermeable maleimide did not inhibit
      [14C]NEM binding to the NEM-reactive residues within TM4, suggesting that the
      putative channel opens toward the cytoplasm. NEM reactivity of the A143C mutant
      was significantly inhibited by Li+. The T140C and D141C mutants showed lower
      affinity for Na+ and Li+ as transport substrates, but their maximal antiporter
      velocities (Vmax) were relatively unaffected. Whereas the I142C and F144C mutants
      completely lost their Li+/H+ antiporter activity, I142C had a lower Vmax for the
      Na+/H+ antiporter. F144C exhibited a markedly lower Vmax and a partially reduced
      affinity for Na+. These results suggest that Thr-140, Asp-141, and Phe-144 are
      located in the end portion of a putative water-filled channel and may provide the
      binding site for Na+, Li+, and/or H+. Furthermore, residues Ile-142 to Phe-144
      may be important for the conformational change that accompanies ion transport in
      NhaA.

PMID- 15263005
TI  - Biochemical analysis of Angelman syndrome-associated mutations in the E3
      ubiquitin ligase E6-associated protein.
AB  - Angelman syndrome is a severe neurological disorder characterized by mental
      retardation, absent speech, ataxia, seizures, and hyperactivity. The gene
      affected in this disorder is UBE3A, the gene encoding the E6-associated protein
      (E6AP) ubiquitin-protein ligase. Most patients have chromosomal deletions that
      remove the entire maternal allele of UBE3A. However, a small subset of patients
      have E6AP point mutations that result in single amino acid changes or short in
      frame deletions that still allow translation of a full-length protein. By
      studying these point mutations in E6AP, we found a strong correlation between
      Angelman-associated mutations and a loss of E3 ubiquitin ligase activity.
      Interestingly the point mutations affect E6AP activity in different ways. Some
      mutant proteins cannot form thiol ester intermediates with ubiquitin, others
      retain the thiol ester formation activity but cannot efficiently transfer
      ubiquitin to a substrate, and still others are unstable in cells. Our results
      suggest that the loss of E6AP catalytic activity and likely the improper
      regulation of E6AP substrate(s) are important in the development of Angelman
      syndrome.

PMID- 15263006
TI  - Morphological adjustment of senescent cells by modulating caveolin-1 status.
AB  - Morphological change is one of the cardinal features of the senescent phenotype;
      for example, senescent human diploid cells have a flat large shape. However, the
      mechanisms underlying such senescence-related morphological alterations have not
      been well studied. To investigate this situation, we characterized the senescence
      dependent changes of cellular structural determinants in terms of their levels
      and activities. These determinants included integrins, focal adhesion complexes,
      and small Rho GTPases, and special emphasis was placed on their relationships
      with caveolin-1 status. We observed that the expression integrin beta(1) and
      focal adhesion kinase (FAK) were increased and that the phosphorylations of FAK
      and paxillin, hallmarks of focal adhesion formation, were also increased in
      senescent human diploid fibroblast cells. Moreover, the Rho GTPases Rac1 and
      Cdc42 were found to be highly activated in senescent cells. In addition, focal
      adhesion complexes and Rho GTPases were up-regulated in the caveolin-rich
      membrane domain in the senescent cells. Activated Rac1 and Cdc42 directly
      interacted with caveolin-1 in senescent cells. Interestingly, caveolin-1 knock
      out senescent cells, achieved by using small interfering RNA and antisense
      oligonucleotide, showed disrupted focal adhesion formation and actin stress
      fibers via the inactivation of FAK, which resulted in morphological adjustment to
      the young cell-like small spindle shape. Based on the results obtained, we
      propose that caveolin-1 plays an important role in senescence-associated
      morphological changes by regulating focal adhesion kinase activity and actin
      stress fiber formation in the senescent cells.

PMID- 15263007
TI  - Transient changes in oxygen tension inhibit osteogenic differentiation and Runx2
      expression in osteoblasts.
AB  - Vascular disruption following bony injury results in a hypoxic gradient within
      the wound microenvironment. Nevertheless, the effects of low oxygen tension on
      osteogenic precursors remain to be fully elucidated. In the present study, we
      investigated in vitro osteoblast and mesenchymal stem cell differentiation
      following exposure to 21% O(2) (ambient oxygen), 2% O(2) (hypoxia), and <0.02%
      O(2) (anoxia). Hypoxia had little effect on osteogenic differentiation. In
      contrast, short-term anoxic treatment of primary osteoblasts and mesenchymal
      precursors inhibited in vitro bone nodule formation and extracellular calcium
      deposition. Cell viability assays revealed that this effect was not caused by
      immediate or delayed cell death. Microarray profiling implicated down-regulation
      of the key osteogenic transcription factor Runx2 as a potential mechanism for the
      anoxic inhibition of differentiation. Subsequent analysis revealed not only a
      short-term differential regulation of Runx2 and its targets by anoxia and
      hypoxia, but a long-term inhibition of Runx2 transcriptional and protein levels
      after only 12-24 h of anoxic insult. Furthermore, we present evidence that Runx2
      inhibition may, at least in part, be because of anoxic repression of BMP2, and
      that restoring Runx2 levels during anoxia by pretreatment with recombinant BMP2
      rescued the anoxic inhibition of differentiation. Taken together, our findings
      indicate that brief exposure to anoxia (but not 2% hypoxia) down-regulated BMP2
      and Runx2 expression, thus inhibiting critical steps in the osteogenic
      differentiation of pluripotent mesenchymal precursors and committed osteoblasts.

PMID- 15263008
TI  - Inhibition of glucosylceramide synthase does not reverse drug resistance in
      cancer cells.
AB  - The multidrug-resistant cancer cell lines NCI/AdR(RES) and MES-SA/DX-5 have
      higher glycolipid levels and higher P-glycoprotein expression than the
      chemosensitive cell lines MCF7-wt and MES-SA. Inhibiting glycolipid biosynthesis
      by blocking glucosylceramide synthase has been proposed to reverse drug
      resistance in MDR cells by causing an increased accumulation of proapoptotic
      ceramide during treatment of cells with cytotoxic drugs. We treated both
      multidrug-resistant cell lines with the glucosylceramide synthase inhibitors PDMP
      (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol), C9DGJ (N-nonyl
      deoxygalactonojirimycin) or C4DGJ (N-butyl-deoxygalactonojirimycin). PDMP
      achieved a significant reversal of drug resistance in agreement with previous
      reports. However, the N-alkylated iminosugars C9DGJ and C4DGJ, which are more
      selective glucosylceramide synthase inhibitors than PDMP, failed to cause any
      reversal of drug resistance despite depleting glycolipids to the same extent as
      PDMP. Our results suggest that (a) inhibition of glucosylceramide synthase does
      not reverse multidrug resistance and (b) the chemosensitization achieved by PDMP
      cannot be caused by inhibition of glucosylceramide synthase alone.

PMID- 15263009
TI  - Factors affecting the level and localization of the transferrin receptor in
      Trypanosoma brucei.
AB  - Transfer of bloodstream-form Trypanosoma brucei variant 221a from calf serum to
      dog serum-based medium induces acute iron starvation, as the transferrin receptor
      (Tf-R) of variant 221a binds dog Tf poorly. We show here that transfer to dog
      serum induces a 3-5-fold increase in Tf-R mRNA and protein within one doubling
      time (8 h). Because iron stores are still high 8 h after transfer, we infer that
      the signal for Tf-R overproduction is the decreased availability of cytosolic
      iron when cellular iron import drops. Up to 30% of the extra Tf-R spills out of
      the flagellar pocket onto the pellicular surface. Because the 5-fold increase in
      Tf-R is accompanied by a 5-fold increase in bovine Tf uptake, the up-regulation
      of Tf-R levels in response to Tf starvation helps the trypanosome to compete for
      limiting amounts of Tf. We noted that Tf-R levels also vary in calf serum medium.
      Cells in dense cultures contain up to 5-fold more Tf-R mRNA and protein than in
      dilute cultures. Only one-tenth of the extra Tf-R reaches the pellicular surface.
      The increase cannot be explained by a lack of Tf or to cell density sensing but
      is due to pericellular hypoxia. Our results show that bloodstream-form
      trypanosomes can regulate the expression of the two Tf-R subunit genes and the
      localization of their gene products in a flexible manner. This flexibility is
      made possible by the promoter-proximal position of the two genes in the variant
      surface glycoprotein expression site.

PMID- 15263010
TI  - Functional and structural characterization of RsbU, a stress signaling protein
      phosphatase 2C.
AB  - RsbU is a positive regulator of the activity of sigmaB, the general stress
      response sigma factor of Gram+ microorganisms. The N-terminal domain of this
      protein has no significant sequence homology with proteins of known function,
      whereas the C-terminal domain is similar to the catalytic domains of PP2C-type
      phosphatases. The phosphatase activity of RsbU is stimulated greatly during the
      response to stress by associating with a kinase, RsbT. This association leads to
      the induction of sigmaB activity. Here we present data on the activation process
      and demonstrate in vivo that truncations in the N-terminal region of RsbU are
      deleterious for the activation of RsbU. This conclusion is supported by
      comparisons of the phosphatase activities of full-length and a truncated form of
      RsbU in vitro. Our determination of the crystal structure of the N-terminal
      domain of RsbU from Bacillus subtilis reveals structural similarities to the
      regulatory domains from ubiquitous protein phosphatases and a conserved domain of
      sigma-factors, illuminating the activation processes of phosphatases and the
      evolution of "partner switching." Finally, the molecular basis of kinase
      recruitment by the RsbU phosphatase is discussed by comparing RsbU sequences from
      bacteria that either possess or lack RsbT.

PMID- 15263011
TI  - Sec/SRP requirements and energetics of membrane insertion of subunits a, b, and c
      of the Escherichia coli F1F0 ATP synthase.
AB  - Previously, the role of YidC in the membrane protein biogenesis of the F(0)
      sector of the Escherichia coli F(1)F(0) ATP synthase was investigated. Whereas
      subunits a and c of the F(1)F(0) ATP synthase were strictly dependent on YidC for
      membrane insertion, subunit b required YidC for efficient insertion (Yi, L.,
      Jiang, F., Chen, M., Cain, B., Bolhuis, A., and Dalbey, R. E. (2003) Biochemistry
      42, 10537-10544). In this paper, we investigated other protein components and
      energetics that are required in the membrane protein assembly of the F(0) sector
      subunits. We show here that the Sec translocase and the signal recognition
      particle (SRP) pathway are required for membrane insertion of subunits a and b.
      In contrast, subunit c required neither the Sec machinery nor the SRP pathway for
      insertion. While the proton motive force was not required for insertion of
      subunits b and c, it was required for translocation of the negatively charged
      periplasmic NH(2)-terminal tail of subunit a, whereas periplasmic loop 2 of
      subunit a could insert in a proton motive force-independent manner. Taken
      together, the in vivo data suggest that subunits a and b are inserted by the
      Sec/SRP pathway with the help of YidC, and subunit c is integrated into the
      membrane by the novel YidC pathway.

PMID- 15263012
TI  - Transcriptional regulation of the human beta-1,4-galactosyltransferase V gene in
      cancer cells: essential role of transcription factor Sp1.
AB  - Beta-1,4-galactosyltransferase (beta-1,4-GalT) V is a constitutively expressed
      enzyme that can effectively galactosylate the GlcNAcbeta1-->6Man group of the
      highly branched N-glycans that are characteristic of tumor cells. Upon malignant
      transformation of cells, the expression of the beta-1,4-GalT V gene increases in
      accordance with the increase in the amounts of highly branched N-glycans. Lectin
      blot analysis showed that the galactosylation of highly branched N-glycans is
      inhibited significantly in SH-SY5Y human neuroblastoma cells by the transfection
      of the antisense beta-1,4-GalT V cDNA, indicating the biological importance of
      the beta-1,4-GalT V for the functions of highly branched N-glycans. We cloned the
      2.3-kb 5'-flanking region of the human beta-1,4-GalT V gene, and we identified
      the region -116/-18 relative to the transcription start site as that having
      promoter activity. The region was found to contain several putative binding sites
      for transcription factors, including AP2, AP4, N-Myc, Sp1, and upstream
      stimulatory factor. Electrophoretic mobility shift assay showed that Sp1 binds to
      nucleotide positions -81/-69 of the promoter region. Mutations induced in the Sp1
      binding site showed that the promoter activity of the beta-1,4-GalT V gene is
      impaired completely in cancer cells. In contrast, the promoter activity increased
      significantly by the transfection of the Sp1 cDNA into A549 human lung carcinoma
      cells. Mithramycin A, which inhibits the binding of Sp1 to its binding site,
      reduced the promoter activation and expression of the beta-1,4-GalT V gene in
      A549 cells. These results indicate that Sp1 plays an essential role in the
      transcriptional activity of the beta-1,4-GalT V gene in cancer cells.

PMID- 15263013
TI  - Crystal structure of ovocleidin-17, a major protein of the calcified Gallus
      gallus eggshell: implications in the calcite mineral growth pattern.
AB  - Ovocleidin-17 (OC17) from Gallus gallus is one of the best candidates to control
      and regulate the deposition of calcium carbonate in the calcified eggshell layer.
      Here, the crystal structure of monomeric OC17, determined at a resolution of 1.5
      A, was refined to a crystallographic R-factor of 20.1%. This is the first protein
      directly involved in a non-pathological biomineralization process resolved by x
      ray diffraction to date. The protein has a mixed alpha/beta structure containing
      a single C-type lectin-like domain. However, although OC17 shares the conserved
      scaffold of the C-type lectins, it does not bind carbohydrates. Nevertheless, in
      vitro OC17 modifies the crystalline habit of calcium carbonate (CaCO3) and the
      pattern of crystal growth at intervals of 5-200 microg/ml. Determining the three
      dimensional structure of OC17 contributes to a better understanding of the
      biological behavior of structurally related biomolecules and of the mechanisms
      involved in eggshell and other mineralization processes.

PMID- 15263014
TI  - FAK and paxillin: regulators of N-cadherin adhesion and inhibitors of cell
      migration?
AB  - FAK and paxillin are important components in integrin-regulated signaling. New
      evidence suggests that these two proteins function in crosstalk between cell
      matrix and cell-cell adhesions. Further, new insight suggests that under some
      conditions these proteins inhibit cell migration, in contrast to their
      established roles in several cell systems as positive regulators of cell adhesion
      and migration.

PMID- 15263015
TI  - Relocation of Aurora B from centromeres to the central spindle at the metaphase
      to anaphase transition requires MKlp2.
AB  - Mitotic kinases of the Polo and Aurora families are key regulators of chromosome
      segregation and cytokinesis. Here, we have investigated the role of MKlp1 and
      MKlp2, two vertebrate mitotic kinesins essential for cytokinesis, in the spatial
      regulation of the Aurora B kinase. Previously, we have demonstrated that MKlp2
      recruits Polo-like kinase 1 (Plk1) to the central spindle in anaphase. We now
      find that in MKlp2 but not MKlp1-depleted cells the Aurora B-INCENP complex
      remains at the centromeres and fails to relocate to the central spindle. MKlp2
      exerts dual control over Aurora B localization, because it is a binding partner
      for Aurora B, and furthermore for the phosphatase Cdc14A. Cdc14A can
      dephosphorylate INCENP and may contribute to its relocation to the central
      spindle in anaphase. We propose that MKlp2 is involved in the localization of
      Plk1, Aurora B, and Cdc14A to the central spindle during anaphase, and that the
      integration of signaling by these proteins is necessary for proper cytokinesis.

PMID- 15263016
TI  - Discs large (Dlg1) complexes in lymphocyte activation.
AB  - T cell antigen recognition involves the formation of a structured interface
      between antigen-presenting and T cells that facilitates the specific transmission
      of activating and desensitizing stimuli. The molecular machinery that organizes
      the signaling molecules and controls their disposition in response to activation
      remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ
      domain-containing protein, is recruited upon activation to cortical actin and
      forms complexes with early participants in T cell activation. Transient
      overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter
      activation. Reduction of Dlg1 expression by RNA interference enhances both CD3-
      and superantigen-mediated NFAT activation. Attenuation of antigen receptor
      signaling appears to be a complex, highly orchestrated event that involves the
      mutual segregation of important elements of the early signaling complex.

PMID- 15263017
TI  - Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to
      regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate.
AB  - Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible
      for calcium release from the endoplasmic reticulum (ER). We show that the anti
      apoptotic protein Bcl-2 (either wild type or selectively localized to the ER)
      significantly inhibited InsP3-mediated calcium release and elevation of cytosolic
      calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the
      level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant
      InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from
      the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of
      InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2
      reduced the open probability of purified InsP3Rs reconstituted into lipid
      bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by
      coimmunoprecipitation and blue native gel electrophoresis. We suggest that this
      functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and
      thereby regulates InsP3-induced calcium release from the ER.

PMID- 15263018
TI  - Cortactin and Crk cooperate to trigger actin polymerization during Shigella
      invasion of epithelial cells.
AB  - Shigella, the causative agent of bacillary dysentery, invades epithelial cells in
      a process involving Src tyrosine kinase signaling. Cortactin, a ubiquitous actin
      binding protein present in structures of dynamic actin assembly, is the major
      protein tyrosine phosphorylated during Shigella invasion. Here, we report that
      RNA interference silencing of cortactin expression, as does Src inhibition in
      cells expressing kinase-inactive Src, interferes with actin polymerization
      required for the formation of cellular extensions engulfing the bacteria.
      Shigella invasion induced the recruitment of cortactin at plasma membranes in a
      tyrosine phosphorylation-dependent manner. Overexpression of wild-type forms of
      cortactin or the adaptor protein Crk favored Shigella uptake, and Arp2/3 binding
      deficient cortactin derivatives or an Src homology 2 domain Crk mutant interfered
      with bacterial-induced actin foci formation. Crk was shown to directly interact
      with tyrosine-phosphorylated cortactin and to condition cortactin-dependent actin
      polymerization required for Shigella uptake. These results point at a major role
      for a Crk-cortactin complex in actin polymerization downstream of tyrosine kinase
      signaling.

PMID- 15263019
TI  - Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through
      IQGAP1 and actin filaments.
AB  - E-cadherin is a key cell-cell adhesion molecule at adherens junctions (AJs) and
      undergoes endocytosis when AJs are disrupted by the action of extracellular
      signals. To elucidate the mechanism of this endocytosis, we developed here a new
      cell-free assay system for this reaction using the AJ-enriched fraction from rat
      liver. We found here that non-trans-interacting, but not trans-interacting, E
      cadherin underwent endocytosis in a clathrin-dependent manner. The endocytosis of
      trans-interacting E-cadherin was inhibited by Rac and Cdc42 small G proteins,
      which were activated by trans-interacting E-cadherin or trans-interacting
      nectins, which are known to induce the formation of AJs in cooperation with E
      cadherin. This inhibition was mediated by reorganization of the actin
      cytoskeleton by Rac and Cdc42 through IQGAP1, an actin filament-binding protein
      and a downstream target of Rac and Cdc42. These results indicate the important
      role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance
      of the E-cadherin-based AJs.

PMID- 15263020
TI  - Synaptotagmins are trafficked to distinct subcellular domains including the
      postsynaptic compartment.
AB  - The synaptotagmin family has been implicated in calcium-dependent
      neurotransmitter release, although Synaptotagmin 1 is the only isoform
      demonstrated to control synaptic vesicle fusion. Here, we report the
      characterization of the six remaining synaptotagmin isoforms encoded in the
      Drosophila genome, including homologues of mammalian Synaptotagmins 4, 7, 12, and
      14. Like Synaptotagmin 1, Synaptotagmin 4 is ubiquitously present at synapses,
      but localizes to the postsynaptic compartment. The remaining isoforms were not
      found at synapses (Synaptotagmin 7), expressed at very low levels (Synaptotagmins
      12 and 14), or in subsets of putative neurosecretory cells (Synaptotagmins alpha
      and beta). Consistent with their distinct localizations, overexpression of
      Synaptotagmin 4 or 7 cannot functionally substitute for the loss of Synaptotagmin
      1 in synaptic transmission. Our results indicate that synaptotagmins are
      differentially distributed to unique subcellular compartments. In addition, the
      identification of a postsynaptic synaptotagmin suggests calcium-dependent
      membrane-trafficking functions on both sides of the synapse.

PMID- 15263021
TI  - Novel signaling pathways mediating reciprocal control of keratinocyte migration
      and wound epithelialization through M3 and M4 muscarinic receptors.
AB  - To test the hypothesis that keratinocyte (KC) migration is modulated by distinct
      muscarinic acetylcholine (ACh) receptor subtypes, we inactivated signaling
      through specific receptors in in vitro and in vivo models of reepithelialization
      by subtype-selective antagonists, small interfering RNA, and gene knockout in
      mice. KC migration and wound reepithelialization were facilitated by M4 and
      inhibited by M3. Additional studies showed that M4 increases expression of
      "migratory" integrins alpha5beta1, alphaVbeta5, and alphaVbeta6, whereas M3 up
      regulates "sedentary" integrins alpha2beta1 and alpha3beta1. Inhibition of
      migration by M3 was mediated through Ca2+-dependent guanylyl cyclase-cyclic GMP
      protein kinase G signaling pathway. The M4 effects resulted from inhibition of
      the inhibitory pathway involving the adenylyl cyclase-cyclic AMP-protein kinase A
      pathway. Both signaling pathways intersected at Rho, indicating that Rho kinase
      provides a common effector for M3 and M4 regulation of cell migration. These
      findings offer novel insights into the mechanisms of ACh-mediated modulation of
      KC migration and wound reepithelialization, and may aid the development of novel
      methods to promote wound healing.

PMID- 15263022
TI  - Roles played by a subset of integrin signaling molecules in cadherin-based cell
      cell adhesion.
AB  - Integrins can intercommunicate with cadherins. Here, we examined their possible
      relationship by use of small interfering RNA-mediated protein knockdown in HeLa
      cells. We found that a subset of integrin signaling molecules, namely Fak and
      paxillin, but not p130 Crk-associated substrate or proline-rich tyrosine kinase
      2, participate in processes regulating N-cadherin-based cell-cell adhesion.
      Paxillin was found to be required primarily for the recruitment of Fak to robust
      focal adhesions. Our results suggest that at least some signals involving Fak are
      linked to a mechanism down-regulating Rac1 activity at the cell periphery, which
      appears to be important for the formation of N-cadherin-based adhesions in motile
      cells. Our analyses simultaneously exemplified the essential role of Fak in the
      maintenance of cell-cell adhesions in collective cell migration, a type of
      migration occurring in embryonic development and carcinoma invasion.

PMID- 15263024
TI  - A role for thymic stromal lymphopoietin in CD4(+) T cell development.
AB  - Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the
      interleukin (IL)-7 receptor alpha chain and a distinctive subunit, TSLP receptor
      (TSLPR), which is most related to the common cytokine receptor gamma chain,
      gamma(c). We have generated TSLPR knockout (KO) mice and found that although
      these mice had normal lymphocyte numbers, gamma(c)/TSLPR double KO mice had a
      greater lymphoid defect than gamma(c) KO mice. This indicates that TSLP
      contributes to lymphoid development and accounts for some of the residual
      lymphoid development in gamma(c) KO mice and presumably in patients with X-linked
      severe combined immunodeficiency. Injection of TSLP into gamma(c) KO mice induced
      the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice
      showed weaker recovery of lymphocyte populations than wild-type (WT) littermates,
      even when neutralizing anti-IL-7 antibodies were injected. Interestingly, TSLP
      preferentially stimulated the proliferation and survival of CD4(+) single
      positive thymocytes and peripheral T cells in vitro. Additionally, CD4(+) T cells
      from TSLPR KO mice expanded less efficiently than WT CD4(+) T cells in irradiated
      hosts, and TSLP preferentially expanded CD4(+) T cells both in vitro and in vivo.
      Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a
      lineage preference for the expansion and survival of CD4(+) T cells.

PMID- 15263023
TI  - A new human somatic stem cell from placental cord blood with intrinsic
      pluripotent differentiation potential.
AB  - Here a new, intrinsically pluripotent, CD45-negative population from human cord
      blood, termed unrestricted somatic stem cells (USSCs) is described. This rare
      population grows adherently and can be expanded to 10(15) cells without losing
      pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts,
      chondroblasts, adipocytes, and hematopoietic and neural cells including
      astrocytes and neurons that express neurofilament, sodium channel protein, and
      various neurotransmitter phenotypes. Stereotactic implantation of USSCs into
      intact adult rat brain revealed that human Tau-positive cells persisted for up to
      3 mo and showed migratory activity and a typical neuron-like morphology. In vivo
      differentiation of USSCs along mesodermal and endodermal pathways was
      demonstrated in animal models. Bony reconstitution was observed after
      transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs.
      Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude
      mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep,
      resulted in up to 5% human hematopoietic engraftment. More than 20% albumin
      producing human parenchymal hepatic cells with absence of cell fusion and
      substantial numbers of human cardiomyocytes in both atria and ventricles of the
      sheep heart were detected many months after USSC transplantation. No tumor
      formation was observed in any of these animals.

PMID- 15263025
TI  - Protein kinase C theta is critical for the development of in vivo T helper (Th)2
      cell but not Th1 cell responses.
AB  - The serine/threonine-specific protein kinase C (PKC)-theta is predominantly
      expressed in T cells and localizes to the center of the immunological synapse
      upon T cell receptor (TCR) and CD28 signaling. T cells deficient in PKC-theta
      exhibit reduced interleukin (IL)-2 production and proliferative responses in
      vitro, however, its significance in vivo remains unclear. We found that pkc
      theta(-/-) mice were protected from pulmonary allergic hypersensitivity responses
      such as airway hyperresponsiveness, eosinophilia, and immunoglobulin E production
      to inhaled allergen. Furthermore, T helper (Th)2 cell immune responses against
      Nippostrongylus brasiliensis were severely impaired in pkc-theta(-/-) mice. In
      striking contrast, pkc-theta(-/-) mice on both the C57BL/6 background and the
      normally susceptible BALB/c background mounted protective Th1 immune responses
      and were resistant against infection with Leishmania major. Using in vitro TCR
      transgenic T cell-dendritic cell coculture systems and antigen concentration
      dependent Th polarization, PKC-theta-deficient T cells were found to
      differentiate into Th1 cells after activation with high concentrations of
      specific peptide, but to have compromised Th2 development at low antigen
      concentration. The addition of IL-2 partially reconstituted Th2 development in
      pkc-theta(-/-) T cells, consistent with an important role for this cytokine in
      Th2 polarization. Taken together, our results reveal a central role for PKC-theta
      signaling during Th2 responses.

PMID- 15263026
TI  - Human autoantibody silencing by immunoglobulin light chains.
AB  - Several newly arising human antibodies are polyreactive, but in normal
      individuals the majority of these potentially autodestructive antibodies are
      removed from the repertoire by receptor editing or B cell deletion in the bone
      marrow. To determine what proportion of naturally arising autoantibodies can be
      silenced by immunoglobulin (Ig) light chain receptor editing, we replaced the
      light chains in 12 such antibodies with a panel of representative Igkappa and
      Iglambda chains. We found that most naturally arising autoantibodies are readily
      silenced by light chain exchange. Thus, receptor editing may account for most
      autoreactive antibody silencing in humans. Light chain complementarity
      determining region (CDR) isoelectric points did not correlate with silencing
      activity, but Iglambda genes were more effective than Igkappa genes as silencers.
      The greater efficacy of Iglambda chains as silencer of autoreactivity provides a
      possible explanation for the expansion and altered configuration of the Iglambda
      locus in evolution.

PMID- 15263027
TI  - Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent
      leishmaniasis and control of concomitant immunity.
AB  - Reactivation of dormant infections causes an immense burden of morbidity and
      mortality in the world at large. Reactivation can occur as a result of
      immunosuppression, environmental insult, or aging; however, the cause of
      reactivation of such infections is often not clear. We have previously shown that
      persistence of the parasite Leishmania major is controlled by endogenous CD4(+)
      CD25(+) regulatory T (T reg) cells. In this report, we show that despite
      efficient parasite clearance at secondary sites of infection, Leishmania
      superinfection can cause disease reactivation at the primary site. Our results
      strongly suggest that T reg cells, whose numbers increase in sites of
      reactivation, are directly responsible for such reactivation. Depletion of
      CD25(+) cells at the time of secondary challenge prevented disease reactivation
      at the site of persistent infection while strengthening the expression of
      immunity at the site of secondary challenge. Finally, transfer of T reg cells
      purified from infected mice into chronically infected mice was sufficient to
      trigger disease reactivation and prevent the expression of an effector memory
      response. Our results demonstrate that after persistence is achieved, an
      equilibrium between T reg cells and effector lymphocytes, which can be disturbed
      by superinfection, controls the efficiency of recall immune responses and disease
      reactivation.

PMID- 15263028
TI  - Clinically approved heterocyclics act on a mitochondrial target and reduce stroke
      induced pathology.
AB  - Substantial evidence indicates that mitochondria are a major checkpoint in
      several pathways leading to neuronal cell death, but discerning critical
      propagation stages from downstream consequences has been difficult. The
      mitochondrial permeability transition (mPT) may be critical in stroke-related
      injury. To address this hypothesis, identify potential therapeutics, and screen
      for new uses for established drugs with known toxicity, 1,040 FDA-approved drugs
      and other bioactive compounds were tested as potential mPT inhibitors. We report
      the identification of 28 structurally related drugs, including tricyclic
      antidepressants and antipsychotics, capable of delaying the mPT. Clinically
      achievable doses of one drug in this general structural class that inhibits mPT,
      promethazine, were protective in both in vitro and mouse models of stroke.
      Specifically, promethazine protected primary neuronal cultures subjected to
      oxygen-glucose deprivation and reduced infarct size and neurological impairment
      in mice subjected to middle cerebral artery occlusion/reperfusion. These results,
      in conjunction with new insights provided to older studies, (a) suggest a class
      of safe, tolerable drugs for stroke and neurodegeneration; (b) provide new tools
      for understanding mitochondrial roles in neuronal cell death; (c) demonstrate the
      clinical/experimental value of screening collections of bioactive compounds
      enriched in clinically available agents; and (d) provide discovery-based evidence
      that mPT is an essential, causative event in stroke-related injury.

PMID- 15263029
TI  - Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129
      specific humanized TCR transgenic mice.
AB  - Amino acid residues 111-129 represent an immunodominant epitope of myelin basic
      protein (MBP) in humans with human leukocyte antigen (HLA)-DRB1*0401 allele(s).
      The MBP 111-129-specific T cell clone MS2-3C8 was repeatedly isolated from a
      patient with multiple sclerosis (MS), suggesting an involvement of MS2-3C8 T
      cells in the pathogenesis. To address the pathogenic potential of the MS2-3C8 T
      cell clone, we generated transgenic (Tg) mice expressing its T cell receptor and
      restriction element, HLA-DRB1*0401, to examine the pathogenic characteristics of
      MS2-3C8 Tg T cells by adoptive transfer into HLA-DRB1*0401 Tg mice. In addition
      to the ascending paralysis typical of experimental autoimmune encephalomyelitis,
      mice displayed dysphagia due to restriction in jaw and tongue movements and
      abnormal gait. In accordance with the clinical phenotype, infiltrates of MS2-3C8
      Tg T cells and inflammatory lesions were predominantly located in the brainstem
      and the cranial nerve roots in addition to the spinal cord and spinal nerve
      roots. Together, these data suggest a pathogenic role of MBP-specific T cells in
      inflammatory demyelination within the brainstem and cranial nerve roots during
      the progression of MS. This notion may help to explain the clinical and
      pathological heterogeneity of MS.

PMID- 15263030
TI  - Peyer's patch dendritic cells process viral antigen from apoptotic epithelial
      cells in the intestine of reovirus-infected mice.
AB  - We explored the role of Peyer's patch (PP) dendritic cell (DC) populations in the
      induction of immune responses to reovirus strain type 1 Lang (T1L).
      Immunofluorescence staining revealed the presence of T1L structural (sigma1) and
      nonstructural (sigmaNS) proteins in PPs of T1L-infected mice. Cells in the
      follicle-associated epithelium contained both sigma1 and sigmaNS, indicating
      productive viral replication. In contrast, sigma1, but not sigmaNS, was detected
      in the subepithelial dome (SED) in association with CD11c(+)/CD8alpha(
      )/CD11b(lo) DCs, suggesting antigen uptake by these DCs in the absence of
      infection. Consistent with this possibility, PP DCs purified from infected mice
      contained sigma1, but not sigmaNS, and PP DCs from uninfected mice could not be
      productively infected in vitro. Furthermore, sigma1 protein in the SED was
      associated with fragmented DNA by terminal deoxy-UTP nick-end labeling staining,
      activated caspase-3, and the epithelial cell protein cytokeratin, suggesting that
      DCs capture T1L antigen from infected apoptotic epithelial cells. Finally, PP DCs
      from infected mice activated T1L-primed CD4(+) T cells in vitro. These studies
      show that CD8alpha(-)/CD11b(lo) DCs in the PP SED process T1L antigen from
      infected apoptotic epithelial cells for presentation to CD4(+) T cells, and
      therefore demonstrate the cross-presentation of virally infected cells by DCs in
      vivo during a natural viral infection.

PMID- 15263031
TI  - SH2D1A regulates T-dependent humoral autoimmunity.
AB  - The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a
      family of chromosome 1-encoded cell surface molecules with costimulatory
      functions mediated in part by the adaptor protein SH2D1A (SLAM-associated
      protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of
      lupus, including the development of hypergammaglobulinemia, autoantibodies
      including anti-double stranded DNA, and renal disease. This protection did not
      reflect grossly defective T or B cell function per se because SH2D1A-deficient
      mice were susceptible to experimental autoimmune encephalomyelitis, a T cell
      dependent disease, and they were capable of mounting normal T-independent antigen
      specific immunoglobulin responses. Instead, T-dependent antibody responses were
      impaired in SH2D1A-deficient mice, reflecting defective germinal center
      formation. These findings demonstrate a specific role for the SLAM-SH2D1A system
      in the regulation of T-dependent humoral immune responses, implicating members of
      the CD150-SH2D1A family as targets in the pathogenesis and therapy of antibody
      mediated autoimmune and allergic diseases.

PMID- 15263035
TI  - National Institutes of Health State-of-the-Science Conference Statement: Symptom
      management in cancer: pain, depression, and fatigue, July 15-17, 2002.
AB  - BACKGROUND: Despite advances in early detection and effective treatment, cancer
      remains one of the most feared diseases. Among the most common side effects of
      cancer and treatments for cancer are pain, depression, and fatigue. Although
      research is producing increasingly hopeful insights into the causes and cures for
      cancer, efforts to manage the side effects of the disease and its treatments have
      not kept pace. The challenge that faces us is how to increase awareness of the
      importance of recognizing and actively addressing cancer-related distress. The
      National Institutes of Health (NIH) convened a State-of-the-Science Conference on
      Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the
      current state of knowledge regarding the management of pain, depression, and
      fatigue in individuals with cancer and to identify directions for future
      research. Specifically, the conference examined how to identify individuals who
      are at risk for cancer-related pain, depression, and/or fatigue; what treatments
      work best to address these symptoms when they occur; and what is the best way to
      deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS:
      A non-advocate, non-Federal, 14-member panel of experts representing the fields
      of oncology, radiology, psychology, nursing, public health, social work, and
      epidemiology prepared the statement. In addition, 24 experts in medical oncology,
      geriatrics, pharmacology, psychology, and neurology presented data to the panel
      and to the conference audience during the first 1.5 days of the conference. The
      panel then prepared its statement, addressing the five predetermined questions
      and drawing on submitted literature, the speakers' presentations, and discussions
      held at the conference. The statement was presented to the conference audience,
      followed by a press conference to allow the panel to respond to questions from
      the media. After its release at the conference, the draft statement was made
      available on the Internet. The panel's final statement is available at
      http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available
      evidence supports a variety of interventions for treating cancer patients' pain,
      depression, and fatigue. Clinicians should routinely use brief assessment tools
      to ask patients about pain, depression, and fatigue and to initiate evidence
      based treatments. Assessment should include discussion about common symptoms
      experienced by cancer patients, and these discussions should continue over the
      duration of the illness. Impediments to effective symptom management in cancer
      patients can arise from different sources and interactions among providers,
      patients and their families, and the health care system. Numerous factors could
      interfere with adequate symptom management. Among these factors are incomplete
      effectiveness of some treatments, a lack of sufficient knowledge regarding
      effective treatment strategies, patient reluctance to report symptoms to
      caregivers, a belief that such symptoms are simply a part of the cancer
      experience that must be tolerated, and inadequate coverage and reimbursement for
      some treatments. Additional research is needed on the definition, occurrence, the
      treatment of pain, depression, and fatigue, alone and in combination, in
      adequately funded prospective studies. The panel also concluded that the state of
      the science in cancer symptom management should be reassessed periodically.

PMID- 15263032
TI  - The scavenger receptor MARCO is required for lung defense against pneumococcal
      pneumonia and inhaled particles.
AB  - Alveolar macrophages (AMs) express the class A scavenger receptor macrophage
      receptor with collagenous structure (MARCO), but its role in vivo in lung defense
      against bacteria and environmental particles has not been studied. We used MARCO
      deficient mice to directly test the in vivo role of AM MARCO in innate defense
      against pneumococcal infection and environmental particles. In a murine model of
      pneumococcal pneumonia, MARCO(-/-) mice displayed an impaired ability to clear
      bacteria from the lungs, increased pulmonary inflammation and cytokine release,
      and diminished survival. In vitro binding of Streptococcus pneumoniae and in vivo
      uptake of unopsonized particles by MARCO(-/-) AMs were dramatically impaired.
      MARCO(-/-) mice treated with the "inert" environmental particle TiO(2) showed
      enhanced inflammation and chemokine expression, indicating that MARCO-mediated
      clearance of inert particles by AMs prevents inflammatory responses otherwise
      initiated by other lung cells. Our findings point to an important role of MARCO
      in mounting an efficient and appropriately regulated innate immune response
      against inhaled particles and airborne pathogens.

PMID- 15263036
TI  - Symptom clusters: the new frontier in symptom management research.
AB  - The majority of clinical studies on pain, fatigue, and depression associated with
      cancer are focused on one symptom. Although this approach has led to some
      advances in our understanding of a particular symptom, patients rarely present
      with a single symptom. Therefore, even though research focused on single symptoms
      needs to continue, it is imperative that symptom management research begins to
      focus on evaluating multiple symptoms, using cross-sectional and longitudinal
      study designs. In addition, research needs to focus on evaluating the
      relationships among multiple symptoms, specific interventions, and patient
      outcomes. One of the initial challenges in research regarding multiple symptoms
      is the terminology that should be used to describe the concept (e.g., symptom
      cluster, symptom constellation). Another significant area related to this aspect
      of symptom management research is determining the nature of clinically
      significant clusters of symptoms and their associated prevalence rates. Equally
      important is the need to determine what types of tools/instruments will provide
      the most valid and reliable data for the assessment of symptom clusters. Other
      areas that need to be considered as related to the assessment of symptom clusters
      include the establishment of cut points for symptom severity that would qualify a
      symptom for inclusion in a cluster; the focus of the assessment; and the choice
      of the outcome measures that will be used to judge the effect of a symptom
      cluster on the patient. In the area of intervention studies for symptom clusters,
      research will need to build on the limited number of clinical trials with single
      symptoms. Additional considerations related to research on symptom clusters
      include the determination of the mechanisms underlying the development of symptom
      clusters; the timing of the measurements for symptom clusters; and statistical
      challenges in the evaluation of symptom clusters. Research on symptom clusters in
      patients with cancer is cutting-edge science and a new frontier in symptom
      management research, and it needs to be done in tandem with research on single
      symptoms.

PMID- 15263038
TI  - Evidence report on the treatment of pain in cancer patients.
AB  - Pain associated with cancer is of widespread concern. We conducted a systematic
      review to evaluate the best available evidence on the efficacy of treatments of
      cancer-related pain. The sources used were MEDLINE, CancerLit, and the Cochrane
      Library from 1966 through April 2001, as well as bibliographies of meta-analyses
      and review articles. We selected randomized controlled trials (RCTs) reporting on
      cancer pain treatment. We recorded the study characteristics, patient and disease
      characteristics, treatment comparisons, outcome measures, and results. The
      methodological quality, applicability, and magnitude of treatment effect for each
      study were graded. We screened 24 822 titles and selected 213 RCTs to address
      specific questions. RCTs of cancer pain control often enroll few subjects, have
      low methodological quality, offer little detail about pain characteristics and
      mechanisms, and involve heterogeneous interventions and outcomes. Nonsteroidal
      anti-inflammatory drugs (NSAIDs), opioids, selected adjuvant medications,
      bisphosphonates, radionuclides, external radiation, palliative chemotherapy, and
      neurolytic celiac plexus block are each efficacious in relieving cancer pain.
      However, the retrieved RCTs indicate no difference in the analgesic efficacies of
      NSAIDs versus other NSAIDs, NSAIDs plus opioids versus NSAIDs alone, or NSAIDs
      versus opioids. Studies of adjuvant medications and behavioral therapies are too
      few and varied to synthesize. RCTs of the analgesic effects of corticosteroids
      were not retrieved in our review, although we did conduct supplemental evidence
      reviews concerning pain control in oral mucositis, acute herpes zoster, or
      postherpetic neuralgia. RCTs confirm the efficacy of diverse interventions in
      relieving cancer pain. The optimal initial and subsequent sequence of choices
      among analgesic drug types cannot be inferred from the retrieved RCTs. Patient
      preferences, the relative efficacy of different routes of drug administration,
      the side effects of analgesics, and the relation of pain control to quality of
      life have not been studied comprehensively. The quantity and quality of
      scientific evidence on cancer pain relief compare unfavorably with evidence
      related to treatment of other high-impact conditions, including cancer itself.
      One contributor to this gap is the heterogeneity of outcomes instruments
      employed: of 218 retrieved trials, there were 125 distinct pain outcomes
      assessed. In the current era of patient-centered care, improving the quality and
      combinability of trials on cancer pain relief should be a high research priority.

PMID- 15263039
TI  - Evidence report on the occurrence, assessment, and treatment of depression in
      cancer patients.
AB  - This evidence-based report reviews the empiric literature on depression in people
      with cancer with a focus on three areas: occurrence, assessment, and treatment.
      More than 350 studies were identified through searches of the English-language
      literature published between 1966 and September 2001. Reports of occurrence are
      limited to prevalence studies, and prevalence rates vary widely despite
      standardized assessments. Rates of major depressive disorder and depressive
      symptoms comorbid with cancer appear to be 10%-25%. Although multiple instruments
      are available for assessing depressive symptoms, a clinical interview using
      Diagnostic and Statistical Manual of Mental Disorders criteria is the standard to
      which assessments are compared. Some data exist for the efficacy of psychosocial
      and pharmacologic treatments for depression in this population. No randomized,
      controlled studies of alternative medicine interventions were identified.

PMID- 15263040
TI  - Evidence report on the occurrence, assessment, and treatment of fatigue in cancer
      patients.
AB  - To determine the occurrence of cancer-related fatigue, the methods used to assess
      it, and the efficacy of the available treatments, we performed literature
      searches that identified English-language publications on these topics. Twenty
      seven studies were identified in which the quantitative estimation of the
      occurrence of cancer-related fatigue was an end point. Fifty-six were judged to
      be relevant to the assessment of fatigue, and 10 randomized controlled clinical
      trials of treatments of cancer-related fatigue were retrieved. The occurrence of
      cancer-related fatigue was found to range from 4% to 91%, depending on the
      population studied and the methods of assessment. Few population-based studies
      and no longitudinal studies of cancer-related fatigue have been performed. The
      methods of fatigue assessment were highly variable. Exercise programs show
      promise to prevent or treat fatigue in some subsets of cancer patients, and the
      use of epoetin alfa for correction of anemia has been shown to ameliorate
      fatigue. The number of subjects in the treatment trials was small and their
      methodologic quality was inconsistent.

PMID- 15263041
TI  - Occurrence of cancer pain.
AB  - Occurrence of cancer pain is highly variable and incompletely understood. Surveys
      are not population-based, are characterized by small heterogeneous samples, and
      provide sketchy data on etiology of pain, pain syndromes, and clinical or
      demographic factors. Moreover, the multiple dimensions of pain have not been
      thoroughly elucidated. Cancer-related pain is caused by the following: 1) direct
      tumor involvement, 2) diagnostic/therapeutic procedures, and 3) side effects or
      toxicities of treatment. Individuals may have more than one type of cancer
      related pain simultaneously. Occurrence rates range from 14% to 100%, and between
      33 and 50% of patients experience pain at some point in the cancer trajectory.
      Rates are higher (e.g., 70%-100%) in palliative care or pain management settings.
      Few researchers have focused solely on specific causes of pain in specific
      patient populations, and only a few included groups at higher risk for pain, such
      as the elderly or underserved. In general, researchers have not followed pain
      over time to determine its course, severity, effects on quality of life and
      functional status, and other related factors. Future researchers should aim to
      acquire specific information on occurrence of pain in a variety of cancer
      diagnoses, settings, and groups of people. Longitudinal designs, in-depth
      exploration of dimensions of pain, and delineation of specific issues in groups
      such as the elderly, children, and vulnerable populations are essential.
      Addressing these critical areas will improve our understanding of the occurrence
      and effects of pain and enhance our ability to provide appropriate interventions,
      thereby increasing patients' quality of life.

PMID- 15263042
TI  - Prevalence of depression in patients with cancer.
AB  - Depression is the psychiatric syndrome that has received the most attention in
      individuals with cancer. The study of depression has been a challenge because
      symptoms occur on a broad spectrum that ranges from sadness to major affective
      disorder and because mood change is often difficult to evaluate when a patient is
      confronted by repeated threats to life, is receiving cancer treatments, is
      fatigued, or is experiencing pain. Although many research groups have assessed
      depression in cancer patients since the 1960s, the reported prevalence (major
      depression, 0%-38%; depression spectrum syndromes, 0%-58%) varies significantly
      because of varying conceptualizations of depression, different criteria used to
      define depression, differences in methodological approaches to the measurement of
      depression, and different populations studied. Depression is highly associated
      with oropharyngeal (22%-57%), pancreatic (33%-50%), breast (1.5%-46%), and lung
      (11%-44%) cancers. A less high prevalence of depression is reported in patients
      with other cancers, such as colon (13%-25%), gynecological (12%-23%), and
      lymphoma (8%-19%). This report reviews the prevalence of depression in cancer
      patients throughout the course of cancer.

PMID- 15263043
TI  - My get up and go got up and went: fatigue in people with cancer.
AB  - Many gaps remain in understanding fatigue across the phases of the cancer
      experience. These include determining the extent to which fatigue is a presenting
      or continuing symptom of cancer or a side effect of cancer treatment, identifying
      those at highest risk of fatigue, defining factors that differentiate between
      those who do and do not experience fatigue, and characterizing fatigue in special
      populations such as those with advanced cancer, children, and elders. This
      article reviews current knowledge of who experiences fatigue, the relationship of
      fatigue to cancer treatment, and the phenomenon of persistent fatigue following
      treatment. Critical elements in the research agenda that need to be addressed
      include the relationship of fatigue to other symptoms of cancer or side effects
      of treatment, mechanisms underlying fatigue and the development of mechanism
      specific approaches to preventing and managing this troublesome symptom.

PMID- 15263044
TI  - Occurrence of symptom clusters.
AB  - Although concurrent symptoms are frequently reported in clinical practice,
      symptom management research has not reflected this reality. Concurrent, related
      symptoms, i.e., symptom clusters, are possibly the next generation of work to be
      done in the area of symptom management. It has been suggested that certain
      clusters of symptoms may have a synergistic effect on future patient outcomes,
      and may predict morbidity. The overall goal of this article is to present initial
      research in the area, along with strategies for development of the concept of
      symptom clusters. In addition, a working definition of symptom clusters is
      offered, as well as current issues with the concept and suggestions for future
      research.

PMID- 15263046
TI  - Assessment of depression in cancer patients.
AB  - It is widely known that depression exists in patients with cancer. The
      prevalence, however, varies widely by study and is often attributable to
      differences in assessment procedures. Attempts to identify accurate methods of
      assessing depression in cancer patients have employed different diagnostic
      approaches, assessment methods (e.g., self-report versus interview), and
      inclusion criteria. Unfortunately, all of these variables affect conclusions that
      can be drawn regarding the presence of depression in cancer patients. Other
      variables that can further affect the assessment of depression in cancer patients
      include individual differences such as the patient's age, gender, race/ethnicity,
      hospitalization status, and type and stage of cancer. Finally, the specific
      assessor and the timing of the assessment also likely affect conclusions about
      depression in cancer patients. This review was designed to succinctly address all
      of the above issues and identify several areas for future research, including
      refining diagnostic criteria for depression in cancer patients; creating cancer
      specific depression measures with appropriate cutoffs; focusing on the issues of
      age, race, ethnicity, subculture, and type and stage of cancer in creating
      depression assessment tools; and exploring the issues of clinical versus
      subclinical depression, who and when to assess, and timely and cost-effective
      ways to assess.

PMID- 15263047
TI  - Assessment of fatigue in cancer patients.
AB  - Increased recognition of the problem of fatigue in cancer patients can be
      attributed, in part, to the development of measures that have provided
      researchers with the tools necessary for quantifying and characterizing fatigue
      and exploring its etiology and treatment. Although a consensus regarding the
      definition of fatigue is lacking, there is general agreement that it is a
      subjective and multidimensional phenomenon whose assessment requires the use of
      self-report methods. Consistent with this view, several multidimensional measures
      of fatigue have been developed and validated for use with cancer patients. These
      measures differ considerably in their format and content and, as with the
      definition of fatigue, there is no consensus at the present time regarding the
      dimensional structure of fatigue. In addition to measuring fatigue on a continuum
      along one or more dimensions, it may also be possible to assess a clinical
      syndrome of cancer-related fatigue. Criteria for assessing fatigue in this manner
      have been proposed and are currently undergoing evaluation. Despite the progress
      that has been made, there are several important unresolved issues in the
      assessment of fatigue in cancer patients. These include how to distinguish
      fatigue from depression, how to use self-reports of fatigue in clinical decision
      making, how to capture temporal changes in fatigue, and how best to address the
      continuing lack of consensus regarding the conceptualization and measurement of
      fatigue.

PMID- 15263048
TI  - Assessment of symptom clusters in people with cancer.
AB  - The control, and ideally prevention, of symptoms such as pain, depression, and
      fatigue is dependent on a comprehensive clinical assessment. Furthermore, to
      advance the science of this field, symptom research requires the use of
      multidimensional instruments with proven validity and reliability in a cancer
      population across the lifespan. Studies demonstrate a significant correlation
      among pain, depression, fatigue, and other symptoms commonly seen throughout the
      course of cancer. Therefore, multidimensional scales incorporating the most
      common symptoms would ensure systematic assessment. Optimally, valid and reliable
      tools that measure symptom clusters would be feasible for use in both clinical
      and research settings. Currently available instruments that measure symptom
      clusters include the Edmonton Symptom Assessment Scale, the M.D. Anderson Symptom
      Inventory, the Memorial Symptom Assessment Scale, the Rotterdam Symptom
      Checklist, the Symptom Distress Scale, and others. Special populations include
      cancer patients with advanced disease, where symptom prevalence is expected to
      increase. Newer tools that attempt to address these populations are the Brief
      Hospice Inventory and the Hospice Quality of Life Index, appropriate for cancer
      patients with more advanced disease. Each of these tools has demonstrated utility
      in measuring symptom severity and quality of life. Few scales have been validated
      in the measurement of symptom clusters in children, in cognitively impaired
      adults, or in non-English speaking patients from various cultural backgrounds.
      The strengths and limitations presented in the clinical and research uses of each
      these instruments will be presented, as will be areas for future investigation.

PMID- 15263049
TI  - Treatment of cancer-related pain.

PMID- 15263050
TI  - Treatment of depression in cancer.
AB  - Depression occurs in about 15% of the general population and is at least two to
      three times more common in patients with cancer. Depression is often difficult to
      diagnose in these patients because of the complexity and constraints of cancer
      care, patient and family reluctance to acknowledge distress, and the presence of
      multiple other symptoms. Both antidepressants and psychotherapy are effective in
      treating depression in patients with cancer, much like in patients with other
      significant medical problems. Precise assessments of the benefits of treating
      depression in these patients are important in weighing them against the costs and
      potential adverse effects. Such estimates are limited by a paucity of randomized,
      placebo-controlled trials and methodological problems in the existing studies
      that reflect some of the clinical difficulties in case-finding, treatment, and
      follow-up of patients with cancer. The existing body of research about depression
      in cancer patients is extremely limited in terms of the number of studies
      published and the number of total patients reported over the last 30 years.
      Moreover, these limited data may not generalize well because of high rates of
      patient dropout and the very limited enrollment of children, adolescents, older
      adults, and minority groups. There is an emerging trend toward simplifying the
      assessment of depression in outpatient cancer care settings and studying
      depression therapies in cohorts of patients with cancer other than those with
      fully characterized depressive disorders.

PMID- 15263051
TI  - Evidence-based treatment for cancer-related fatigue.
AB  - Despite the high prevalence of cancer-related fatigue and its documented negative
      effects on patients' quality of life, limited evidence is available to support
      interventions to prevent or treat cancer-related fatigue. Both pharmacologic and
      nonpharmacologic interventions have been tested, with aerobic exercise programs
      and anemia correction by erythropoietin demonstrating greatest effectiveness.
      This article reviews the available evidence and describes gaps in knowledge.
      Recommendations for future research on interventions for cancer-related fatigue
      are presented.

PMID- 15263052
TI  - Treatment of symptom clusters: pain, depression, and fatigue.
AB  - There is not yet sufficient evidence-based experience for the coordinated
      treatment of three symptoms that cluster in cancer: pain, depression, and
      fatigue. Each symptom taken individually has accepted treatment modalities. With
      some overlap between these symptoms, established treatments for one symptom may
      "cross-over" and reduce the burden of one, or both of the others. To optimize
      patient care in advance of the evidence basis, attention to these symptoms is
      value-added for patients and their families. Standardized screening using the
      Distress Thermometer for physical, practical, emotional, or spiritual symptoms
      helps effectively identify patients whose symptoms warrant attention. Cancer
      Supportive Services, an innovative program at the Continuum Cancer Centers of New
      York at Beth Israel and St. Luke's-Roosevelt, provides comprehensive intervention
      throughout the trajectory of care for pain, depression, and fatigue. These
      services are provided in tandem with efforts to cure or contain the cancer.
      Cancer Supportive Services sets up a natural entry point to survivors' follow-up
      or end-of-life care. Such an effort reinforces a basic principle that active
      symptom management is integral to each patient encounter in the cancer treatment
      setting.

PMID- 15263053
TI  - Pain: impediments and suggestions for solutions.
AB  - Pain is a common and devastating symptom of cancer that can be effectively
      controlled with currently available pharmacological and non-pharmacological
      therapies. Unfortunately, there continue to be reports that half of patients with
      cancer have inadequate relief of their pain with devastating effects on their
      quality of life and functional status. Systematic efforts to understand and
      eliminate the barriers to effective pain control are essential if we are to make
      pain assessment and management an integral part of cancer care. Documented
      impediments are related to health care professionals; patients, families, and the
      public; and the health care, reimbursement, and drug regulatory systems. A
      research agenda that focuses on closing the gap between current knowledge and
      practice is essential to assuring that people with cancer are no longer subjected
      to the agony of unrelieved pain.

PMID- 15263054
TI  - Barriers to the treatment of depression in cancer patients.
AB  - Major depressive disorder is a relapsing syndrome with grave morbidity and
      mortality. Much like asthma, it has a genetic predisposition and environmental
      triggers. Specific antidepressant medications alone, tested in randomized,
      placebo-controlled studies, show that this is a treatable condition with 65%-70%
      clinical response. Treatment guidelines written for psychiatric patients and
      patients in primary care clarify the role of medications and psychotherapy.
      Physicians are compelled to treat syndromes that are serious and treatable, but
      barriers to diagnosis and treatment of major depressive disorder in cancer
      patients include two major barriers to quality medical care generally:
      uncertainty and cost. Given uncertainty about diagnosis and treatment, cancer
      physicians with limited time avoid questions about emotions. Cases of depression
      are often missed. Mental health specialists often work in systems that are
      separated from oncologists by location, organization, and insurance. Most
      successful interventions to improve treatment of depressive disorders require
      multiple strategies: clinical education, enhanced role of nurses, and integrated
      oncology and specialist care. Recent strategies in oncology settings are
      reviewed. Research concepts to improve outcomes in treatment of depression
      include staging of depressive disorder in cancer to reveal prognosis, evaluation
      of depression outcomes in the context of one tumor type, new organizational
      models in the acute cancer setting, use of the cancer protocol, and assessment of
      access to care of depression in cancer survivors. Major depressive disorder in
      cancer is staged by positive past history, comorbid anxiety disorder or substance
      abuse, use of specific cancer medications that destabilize mood, and active
      cancer or no evidence of disease.

PMID- 15263055
TI  - Impediments and solutions to improving the management of cancer-related fatigue.

PMID- 15263056
TI  - Symptom clusters: impediments and suggestions for solutions.

PMID- 15263057
TI  - Gender differences in pain, fatigue, and depression in patients with cancer.
AB  - A quick review of virtually any research topic documents the pervasiveness of sex
      and gender bias throughout all of science. A large portion of both animal and
      human research has been, and continues to be, done primarily with male subjects.
      This gender bias influences research results and often leads to inappropriate and
      questionable generalizations of research findings, usually from studies done with
      male participants to females. Needless to say, this bias exists in symptom
      management research on pain, fatigue, and depression in patients with cancer.
      This article reviews the evidence from the studies on gender differences in pain,
      fatigue, and depression in patients with cancer. It should be noted that research
      studies on gender differences in cancer-related pain, fatigue, and depression are
      minimal in number, are restricted to studies of the differences in prevalence
      rates and severity scores, and for the most part have yielded inconsistent
      results. Additional investigations are warranted to determine whether the gender
      differences in prevalence rates and severity of these symptoms represent
      clinically meaningful differences. If these gender differences are substantiated,
      these findings will guide the design of studies to elucidate the underlying
      mechanisms for these differences, as well as the development and testing of
      gender specific interventions to treat cancer-related pain, fatigue, and
      depression.

PMID- 15263058
TI  - Palliative care in children with cancer: which child and when?
AB  - At a time of increasing interest in palliative care in pediatrics, pediatric
      oncology programs may be failing to deliver adequate palliation to children with
      cancer. In a recent study, parents of children who died on a pediatric oncology
      service reported that despite treatment at the end of life, their children's
      suffering was not adequately relieved and that parents were more likely than
      caregivers to recognize their children's suffering. Why do pediatric oncologists
      fail? First, death in children from cancer is a rare event. Second, few
      prospective trials in the field of pediatric palliative care describe and
      quantify symptoms during cure-directed care or at the end of life. This leads to
      a lack of evidence-based practice and forces the clinician to use personal
      experience and trial-by-error medical care. Third, pediatric oncologists and
      those charged with developing pediatric palliative care programs must deal with
      the different physiologic and developmental stages encountered while caring for
      infants, children, and adolescents. Fourth, education is needed for pediatric
      oncology caregivers in many areas of palliative care. Finally, reimbursement
      issues surround the palliative care field and are a major hindrance in developing
      effective integrated palliative care teams. These factors have also made it
      difficult to perform palliative care research in children. When discussing
      palliative care in children with cancer, where few die but many suffer, a
      paradigm shift must occur that does not equate palliative care with end-of-life
      care. A model on how we might make the transition from symptom control that we
      should offer to every patient to end-of-life care is discussed.

PMID- 15263059
TI  - Symptom management in the elderly cancer patient: fatigue, pain, and depression.
AB  - Patients who are > or =65 years of age are the fastest growing segment of the
      U.S. population. These patients with already existing physiologic decline and
      comorbidities, when diagnosed with cancer, provide considerable challenges in
      management issues. Along with therapy for the tumor the practicing oncologist
      must also keep in mind the various symptoms, like fatigue, pain, and depression,
      that may occur due to the tumor itself or due to therapy. The prevalence of
      fatigue is greater than 50-70% in advanced cancer. The tools to measure fatigue
      are all subjective in nature and no one tool has been tested in the elderly
      cancer patient. Treatment of fatigue in the elderly may involve education,
      antidepressants, treatment of anemia, exercise, and use of psychostimulants. Pain
      is present is 80% of elderly patients with advanced cancer. Pain should be
      assessed in a systematic way and it has been shown that the Visual Descriptor
      Scale is the tool most preferred by the elderly. Several guidelines for
      management of pain exist and options include acetaminophen, nonsteroidal anti
      inflammatory drugs, opioids, adjuvant analgesics, and education of patients and
      caregivers. Depression is also a prevalent symptom arising from a variety of
      causes. There are many validated tools to measure depression in the elderly like
      the Geriatric Depression Scale. Treatment includes use of education, selective
      serotonin reuptake inhibitors, psychotherapy, and electroconvulsive therapy.
      There exists an interplay of many of these symptoms and quite often they can
      occur simultaneously in the elderly cancer patient. Future research is needed to
      expand our base of knowledge on the occurrence and management of each of these
      symptoms and to better understand how aging systems interact with these phenomena
      to produce unique situations in older adults.

PMID- 15263060
TI  - Intracellular inhibition of hepatitis C virus (HCV) internal ribosomal entry site
      (IRES)-dependent translation by peptide nucleic acids (PNAs) and locked nucleic
      acids (LNAs).
AB  - Hepatitis C virus (HCV) is the major etiological agent of non-A, non-B hepatitis.
      Current therapies are not effective in all patients and can result in the
      generation of resistant mutants, leading to a need for new therapeutic options.
      HCV has an RNA genome that contains a well-defined and highly conserved secondary
      structure within the 5'-untranslated region. This structure is known as the
      internal ribosomal entry site (IRES) and is necessary for translation and viral
      replication. Here, we test the hypothesis that antisense peptide nucleic acid
      (PNA) and locked nucleic acid (LNA) oligomers can bind key IRES sequences and
      block translation. We used lipid-mediated transfections to introduce PNAs and
      LNAs into cells. Our data suggest that PNAs and LNAs can invade critical
      sequences within the HCV IRES and inhibit translation. Seventeen base PNA or LNA
      oligomers targeting different regions of the HCV IRES demonstrated a sequence
      specific dose-response inhibition of translation with EC(50) values of 50-150 nM.
      Inhibition was also achieved by PNAs ranging in length from 15 to 21 bases. IRES
      directed inhibition of gene expression widens the range of mechanisms for
      antisense inhibition by PNAs and LNAs and may provide further therapeutic lead
      compounds for the treatment of HCV.

PMID- 15263061
TI  - Intercellular communication between germ line and somatic line is utilized to
      control the transcription of ZAM, an endogenous retrovirus from Drosophila
      melanogaster.
AB  - ZAM is an long terminal repeat (LTR) retrotransposon from Drosophila melanogaster
      that bears striking resemblance to the vertebrate retroviruses, in their
      structure and replication cycle. This element transposes via an RNA intermediate
      and its reverse transcription, and ultimately inserts copies within the germ
      line. In this paper, we show that intercellular communication established between
      the germ line cells and the somatic follicle cells is used to initiate the
      replication cycle of ZAM. ZAM has been shown to be transcribed in the follicle
      cells located at the posterior pole of the oocyte. Here, we determine the cis
      regulatory elements necessary for its somatic expression, and show that they
      respond to the EGF-receptor signaling pathway and its activation by the ligand
      Gurken emitted by the germ line. We further show that the ETS-transcription
      factor Pointed2 acting downstream of this pathway acts as a trans-regulatory
      factor and targets a specific cis-regulatory binding site located within the ZAM
      LTR. Our data give an insight into the molecular mechanism for how intercellular
      communications between germ cells and somatic cells may be used by endogenous
      retroviruses to control their replication, and thereby specify their intrinsic
      and highly restricted expression in the reproductive apparatus.

PMID- 15263062
TI  - Synthesis and physical and physiological properties of 4'-thioRNA: application to
      post-modification of RNA aptamer toward NF-kappaB.
AB  - We report herein full details of the preparation of 4'-thiouridine, -cytidine, 
      adenosine and -guanosine phosphoramidites based on our synthetic protocol via the
      Pummerer reaction. Fully modified 4'-thioRNAs containing four kinds of 4'
      thioribonucleoside units were prepared according to the standard RNA synthesis.
      The T(m) values and thermodynamic parameters of a series of duplexes were
      determined by UV melting and differential scanning calorimetry (DSC)
      measurements. The resulting overall order of thermal stabilities for the duplexes
      was 4'-thioRNA:4'-thioRNA >> 4'-thioRNA:RNA > RNA:RNA > RNA:DNA > 4'-thioRNA:DNA.
      In addition, it was shown that the dominant factor in the stability of the
      duplexes consisting of 4'-thioRNA was enthalpic in character. The CD spectra of
      not only 4'-thioRNA:RNA and 4'-thioRNA:4'-thioRNA but also 4'-thioRNA:DNA were
      all similar to those of duplexes in the A-conformation. The stability of 4'
      thioRNA in human serum was 600 times greater than that of natural RNA. Neither
      the RNA:RNA nor the 4'-thioRNA:4'-thioRNA duplexes were digested under the same
      conditions. The first example of a post-modification of an RNA aptamer by 4'
      thioribonucleoside units was demonstrated. Full modification of the aptamer
      thioRNA3 resulted in complete loss of binding activity. In contrast,
      modifications at positions other than the binding site were tolerated without
      loss of binding activity. The post-modified RNA aptamer thioRNA5 was thermally
      stabilized and resistant toward nuclease digestion. The results presented in this
      paper will, it is hoped, contribute to the development of 4'-thioRNA as a new
      generation of artificial RNA.

PMID- 15263063
TI  - Protein-DNA footprinting by endcapped duplex oligodeoxyribonucleotides.
AB  - Oligodeoxyribonucleotides (5'-phosphorylated) of varying lengths were capped
      using a polyamide linker to form thermodynamically stable, endcapped DNA duplexes
      containing 8-14 bp. We have employed these endcapped DNA duplexes as tools to
      determine the DNA footprint of T4 DNA ligase. By high-performance liquid
      chromatography and PAGE analysis of the ligation mixtures of the endcapped DNA
      duplexes, we have found that by varying the lengths and the position of the nick,
      we can determine the minimal DNA-binding site as well as the mode of binding
      (symmetrical or asymmetrical binding) by the enzyme. The results of the study
      revealed that a 11 bp endcapped duplex was the shortest duplex effectively
      ligated. Dependence of ligation efficiency on nick position demonstrates that T4
      DNA ligase bound asymmetrically to its DNA substrate. The use of a set of
      thermodynamically stable endcapped deoxyribonucleoside duplexes as a tool to
      elucidate the DNA footprint provides an efficient strategy for footprinting,
      which avoids ambiguities associated with chemical and biochemical footprinting
      methods.

PMID- 15263064
TI  - New separation-free assay technique for SNPs using two-photon excitation
      fluorometry.
AB  - A new separation-free method for detection of single nucleotide polymorphisms
      (SNPs) is described. The method is based on the single base extension principle,
      fluorescently labeled dideoxy nucleotides and two-photon fluorescence excitation
      technology, known as ArcDia trade mark TPX technology. In this assay technique,
      template-directed single base extension is carried out for primers which have
      been immobilized on polymer microparticles. Depending on the sequence of the
      template DNA, the primers are extended either with a labeled or with a non
      labeled nucleotide. The genotype of the sample is determined on the basis of two
      photon excited fluorescence of individual microparticles. The effect of various
      assay condition parameters on the performance of the assay method is studied. The
      performance of the new assay method is demonstrated by genotyping the SNPs of
      human individuals using double-stranded PCR amplicons as samples. The results
      show that the new SNP assay method provides sensitivity and reliability
      comparable to the state-of-the-art SNaPshot trade mark assay method.
      Applicability of the new method in routine laboratory use is discussed with
      respect to alternative assay techniques.

PMID- 15263065
TI  - The phox homology (PX) domain protein interaction network in yeast.
AB  - The phox homology (PX) domain is a phosphoinositide-binding domain that is
      conserved from yeast to human. Here we show for the first time by genome-wide two
      hybrid screens and in vitro binding assays that the PX domain is a bona fide
      protein interaction domain. The yeast PX domain-only proteins Grd19p (YOR357C)
      and Ypt35p (YHR105W), as well as the isolated PX domains from Mvp1p (YMR004W),
      Snx42p/Cvt20p/Atg20p (YDL113C), Vam7p (YGL212W), and Vps17p (YOR132W), yielded a
      total of 40 reproducible two-hybrid interactions. Thirty-five interactions were
      found for the full-length proteins of Bem1p (YBR200W), Snx42p, Snx4p/Cvt13p
      (YJL036W), Vam7p, Vps5p (YOR069W), and Vps17p, but these appear not to require
      the PX domain, because these interactions could not be reproduced with PX-only
      baits. Interactions of Grd19p, Vam7p, Vps5p, Vps17p, and Ypt35p with members of
      the Yip1p family of proteins were detected consistently and were verified by in
      vitro binding assays. The N-terminal cytoplasmic domain of Yip1p and Yif1p
      mediates these interactions with PX domains. A mutation in the lipid-binding
      pocket of Ypt35p that reduces lipid binding markedly does not affect these PX
      domain protein interactions, arguing that lipid binding uses a different
      interaction surface than protein binding.

PMID- 15263066
TI  - Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly
      isolated neurons from nucleus accumbens.
AB  - Although there is now evidence of a role for N-methyl-D-aspartate (NMDA)
      receptors in nucleus accumbens (NAcc) neurons in the effects of chronic opiate
      treatment, the cellular and molecular mechanisms underlying this phenomenon are
      still unclear. Therefore, we studied the effects of chronic morphine on the
      pharmacological and biophysical properties of NMDA receptors in freshly isolated
      medium spiny neurons from NAcc. We found that chronic morphine treatment did not
      alter the affinity for NMDA receptor agonists such as glutamate, homoquinolinic
      acid, and NMDA, but decreased the affinity of glycine, the allosteric NMDA
      receptor coagonist, from 2.24 +/- 0.15 microM to 5.1 +/- 1.45 microM. Chronic
      morphine treatment also altered the affinity of two noncompetitive NMDA receptor
      antagonists, 7-chloro-kynurenic acid and ifenprodil. However, morphine had no
      effect on a third antagonist, D-(-)-2-amino-5-phosphonopentanoic acid. Single
      exponential fits of desensitized NMDA current tails gave tau values ranging from
      0.5 to 4 s in neurons from both control and morphine-treated rats. However, a
      shift to the left of the distribution of tau values after morphine treatment
      revealed that NMDA current desensitization rate was accelerated in a majority of
      NAcc neurons. Taken together with our recent molecular studies, our data are
      consistent with a shift away from NMDA receptor subunit (NR) NR2B and 2C function
      toward increased NR2A subunit expression or function after chronic morphine, a
      process that could alter excitability and integrative properties and may
      represent a neuroadaptation of NAcc medium spiny neurons underlying morphine
      dependence.

PMID- 15263067
TI  - Inhibition of activator protein 1 by barbiturates is mediated by differential
      effects on mitogen-activated protein kinases and the small G proteins ras and rac
      1.
AB  - Barbiturates are known to suppress protective immunity, and their therapeutic use
      is associated with nosocomial infections. Although barbiturates inhibit T cell
      proliferation, differentiation, and cytokine synthesis, only thiobarbiturates
      markedly reduce the activation of immune regulatory transcription factors such as
      nuclear factor-kappaB and nuclear factor of activated T cells. In this study, we
      investigated barbiturate-mediated effects on the regulation of the transcription
      factor activator protein 1 (AP-1) in primary T lymphocytes. We show that both
      thiobarbiturates and their oxy-analogs inhibit AP-1-dependent gene expression and
      AP-1 complex formation at clinically relevant doses. Furthermore, mitogen
      activated protein (MAP) kinase activity, which transcriptionally and
      posttranslationally regulates AP-1 complex formation, is suppressed by most
      barbiturates. CD3/CD28- or phorbol 12-myristate 13-acetate (PMA)/ionomycin
      induced p38 and extracellular signal-regulated kinase 1/2 phosphorylation or c
      jun NH2-terminal kinase (JNK) 1/2 kinase activity was significantly diminished by
      pentobarbital, thiamylal, secobarbital, or methohexital treatment. These
      barbiturates also inhibited the initiators of the MAP kinase cascade, the small G
      proteins ras and rac-1, and prevented binding to their partners raf-1 and PAK,
      respectively. Thiopental, unlike the other barbiturates, only reduced ras and JNK
      activity upon direct CD3/CD28 receptor engagement. Contrarily, upon PMA/ionomycin
      stimulation, thiopental blocked AP-1-dependent gene expression independently of
      the small G protein ras and MAP kinases, thus suggesting an additional, unknown
      mechanism of AP-1 regulation. In conclusion, our results contribute to the
      explanation of a clinically manifested immune suppression in barbiturate-treated
      patients and support the idea of a MAP kinase-independent regulation of AP-1 by
      PKC and calcium in human T cells.

PMID- 15263068
TI  - Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness
      to reovirus infection.
AB  - Reovirus is a benign human virus that was recently found to have oncolytic
      properties and is currently in clinical trials as a potential cancer therapy. We
      have previously demonstrated that activation of Ras signaling, a common event in
      cancer, renders cells susceptible to reovirus oncolysis. In this study, we
      investigate which elements downstream of Ras are important in reovirus infection.
      By using a panel of NIH 3T3 cells transformed with activated Ras mutated in the
      effector-binding domain, we found that only the RasV12G37 mutant, which was
      unable to signal to Raf or phosphatidylinositol 3-kinase but retained signaling
      capability to guanine nucleotide-exchange factors (GEFs) for the small G protein,
      Ral (known as RalGEFs), was permissive to reovirus. Expression of the activated
      mutant of the RalGEF, Rlf, also allowed reovirus replication. Specific inhibition
      of the Ral pathway by using dominant-negative RalA rendered normally permissive H
      Ras cells (cells expressing activated Ras) resistant to reovirus. To further
      identify elements downstream of RalGEF that promote reovirus infection, we used
      chemical inhibitors of the downstream signaling elements p38 and JNK. We found
      that reovirus infection was blocked in the presence of the p38 inhibitor but not
      the JNK inhibitor. Together, these results implicate a Ras/RalGEF/p38 pathway in
      the regulation of reovirus replication and oncolysis.

PMID- 15263069
TI  - Southern Peru desert shattered by the great 2001 earthquake: implications for
      paleoseismic and paleo-El Nino-Southern Oscillation records.
AB  - In the desert region around the coastal city of Ilo, the great southern Peru
      earthquake of June 23, 2001 (8.2-8.4 moment magnitude), produced intense and
      widespread ground-failure effects. These effects included abundant landslides,
      pervasive ground cracking, microfracturing of surficial hillslope materials,
      collapse of drainage banks over long stretches, widening of hillside rills, and
      lengthening of first-order tributary channels. We have coined the term "shattered
      landscape" to describe the severity of these effects. Long-term consequences of
      this landscape shattering are inferred to include increased runoff and sediment
      transport during postearthquake rainstorms. This inference was confirmed during
      the first minor postearthquake rainstorm there, which occurred in June and July
      of 2002. Greater amounts of rainfall in this desert region have historically been
      associated with El Nino events. Previous studies of an unusual paleoflood deposit
      in this region have concluded that it is the product of El Nino-generated
      precipitation falling on seismically disturbed landscapes. The effects of the
      2001 earthquake and 2002 rainstorm support that conclusion.

PMID- 15263070
TI  - A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered
      metabolism.
AB  - Heme is a common factor linking several metabolic perturbations in Alzheimer's
      disease (AD), including iron metabolism, mitochondrial complex IV, heme
      oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was
      altered in temporal lobes obtained at autopsy from AD patients and age-matched
      nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and
      26% less heme-a (P = 0.16) compared with controls, resulting in a highly
      significant 2.9-fold decrease in heme-a/heme-b ratio (P < 0.001). Moreover, the
      strong Pearson correlation between heme-a and heme-b measured in control
      individuals (r(2) = 0.66, P < 0.002, n = 11) was abolished in AD subjects (r(2) =
      0.076, P = 0.39, n = 12). The level of ferrochelatase (which makes heme-b in the
      mitochondrial matrix) in AD subjects was 4.2 times (P < 0.04) that in nondemented
      controls, suggesting up-regulated heme synthesis. To look for a possible
      connection between these observations and established mechanisms in AD pathology,
      we examined possible interactions between amyloid beta (A beta) and heme. A
      beta((1-40)) and A beta((1-42)) induced a redshift of 15-20 nm in the spectrum of
      heme-b and heme-a, suggesting that heme binds A beta, likely to one or more of
      the histidine residues. Lastly, in a tissue culture model, we found that
      clioquinol, a metal chelator in clinical trials for AD therapy, decreased
      intracellular heme. In light of these observations, we have proposed a model of
      AD pathobiology in which intracellular A beta complexes with free heme, thereby
      decreasing its bioavailability (e.g., heme-a) and resulting in functional heme
      deficiency. The model integrates disparate observations, including A beta,
      mitochondrial dysfunction, cholesterol, and the proposed efficacy of clioquinol.

PMID- 15263072
TI  - Conformation and orientation of a protein folding intermediate trapped by
      adsorption.
AB  - Although adsorption-induced conformational changes of proteins play an essential
      role during protein adsorption on interfaces, detailed information about these
      changes is lacking. To further the current understanding of protein adsorption,
      in this study, the orientation, conformation, and local stability of bovine alpha
      lactalbumin (BLA) adsorbed on polystyrene nanospheres is characterized at the
      residue level by hydrogen/deuterium exchange and 2D NMR spectroscopy. Most of the
      adsorbed BLA molecules have conformational properties similar to BLA molecules in
      the acid-induced molten globule state (A state). A folding intermediate of BLA is
      thus induced and trapped by adsorption of the protein on the hydrophobic
      interface. Several residues, clustered on one side of the adsorbed folding
      intermediate of BLA, have altered amide proton exchange protection factors
      compared to those of the A state of BLA. This side preferentially interacts with
      the interface and includes residues in helix C, the calcium binding site, and
      part of the beta-domain. Local unfolding of this interacting part of the adsorbed
      protein seems to initiate the adsorption-induced unfolding of BLA. Adsorption
      induced protein unfolding apparently resembles more the mechanical unfolding of a
      protein than the global unfolding of a protein as induced by denaturant, pH, or
      pressure. 2D macromolecular crowding prevented the minority of adsorbed BLA
      molecules, which arrived late at the interface, to unfold to the A state. Protein
      adsorption is a novel and challenging approach to probe features of the free
      energy landscapes accessible to unfolding proteins.

PMID- 15263071
TI  - Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli
      ribosomes.
AB  - 15N-(1)H NMR spectroscopy has been used to probe the dynamic properties of
      uniformly (15)N labeled Escherichia coli ribosomes. Despite the high molecular
      weight of the complex ( approximately 2.3 MDa), [(1)H-(15)N] heteronuclear single
      quantum correlation spectra contain approximately 100 well resolved resonances,
      the majority of which arise from two of the four C-terminal domains of the stalk
      proteins, L7/L12. Heteronuclear pulse-field gradient NMR experiments show that
      the resonances arise from species with a translational diffusion constant
      consistent with that of the intact ribosome. Longitudinal relaxation time (T(1))
      and T(1 rho) (15)N-spin relaxation measurements show that the observable domains
      tumble anisotropically, with an apparent rotational correlation time
      significantly longer than that expected for a free L7/L12 domain but much shorter
      than expected for a protein rigidly incorporated within the ribosomal particle.
      The relaxation data allow the ribosomally bound C-terminal domains to be oriented
      relative to the rotational diffusion tensor. Binding of elongation factor G to
      the ribosome results in the disappearance of the resonances of the L7/L12
      domains, indicating a dramatic reduction in their mobility. This result is in
      agreement with cryoelectron microscopy studies showing that the ribosomal stalk
      assumes a single rigid orientation upon elongation factor G binding. As well as
      providing information about the dynamical properties of L7/L12, these results
      demonstrate the utility of heteronuclear NMR in the study of mobile regions of
      large biological complexes and form the basis for further NMR studies of
      functional ribosomal complexes in the context of protein synthesis.

PMID- 15263073
TI  - Phylogeny and diversification of the largest avian radiation.
AB  - The order Passeriformes ("perching birds") comprises extant species diversity
      comparable to that of living mammals. For over a decade, a single phylogenetic
      hypothesis based on DNA-DNA hybridization has provided the primary framework for
      numerous comparative analyses of passerine ecological and behavioral evolution
      and for tests of the causal factors accounting for rapid radiations within the
      group. We report here a strongly supported phylogenetic tree based on two single
      copy nuclear gene sequences for the most complete sampling of passerine families
      to date. This tree is incongruent with that derived from DNA-DNA hybridization,
      with half of the nodes from the latter in conflict and over a third of the
      conflicts significant as assessed under maximum likelihood. Our historical
      framework suggests multiple waves of passerine dispersal from Australasia into
      Eurasia, Africa, and the New World, commencing as early as the Eocene,
      essentially reversing the classical scenario of oscine biogeography. The revised
      history implied by these data will require reassessment of comparative analyses
      of passerine diversification and adaptation.

PMID- 15263074
TI  - Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of
      infancy.
AB  - Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel
      alpha(1) subunit (Na(V)1.1), are associated with at least two forms of epilepsy,
      generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of
      infancy (SMEI). We examined the functional properties of five SMEI mutations by
      using whole-cell patch-clamp analysis of heterologously expressed recombinant
      human SCN1A. Two mutations (F902C and G1674R) rendered SCN1A channels
      nonfunctional, and a third allele (G1749E) exhibited minimal functional
      alterations. However, two mutations within or near the S4 segment of the fourth
      repeat domain (R1648C and F1661S) conferred significant impairments in fast
      inactivation, including persistent, noninactivating channel activity resembling
      the pattern of channel dysfunction observed for alleles associated with
      generalized epilepsy with febrile seizures plus. Our data provide evidence for a
      range of SCN1A functional abnormalities in SMEI, including gain-of-function
      defects that were not anticipated in this disorder. Our results further indicate
      that a complex relationship exists between phenotype and aberrant sodium channel
      function in these inherited epilepsies.

PMID- 15263075
TI  - Transparallel processing by hyperstrings.
AB  - Human vision research aims at understanding the brain processes that enable us to
      see the world as a structured whole consisting of separate objects. To explain
      how humans organize a visual pattern, structural information theory starts from
      the idea that our visual system prefers the organization with the simplest
      descriptive code, that is, the code that captures a maximum of visual regularity.
      Empirically, structural information theory gained support from psychological data
      on a wide variety of perceptual phenomena, but theoretically, the computation of
      guaranteed simplest codes remained a troubling problem. Here, the graph
      theoretical concept of "hyperstrings" is presented as a key to the solution of
      this problem. A hyperstring is a distributed data structure that allows a search
      for regularity in O(2(N)) strings as if only one string of length N were
      concerned. Thereby, hyperstrings enable transparallel processing, a previously
      uncharacterized form of processing that might also be a form of cognitive
      processing.

PMID- 15263076
TI  - IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular
      receptor cluster in lipid rafts of T cells.
AB  - The private alpha-chains of IL-2 and IL-15 receptors (IL-2R and IL-15R) share the
      signaling beta- and gamma(c)-subunits, resulting in both common and contrasting
      roles of IL-2 and IL-15 in T cell function. Knowledge of the cytokine-dependent
      subunit assembly is indispensable for understanding the paradox of distinct
      signaling capacities. By using fluorescence resonance energy transfer and
      confocal microscopy, we have shown that IL-2R alpha, IL-15R alpha, IL-2/15R beta
      and gamma(c)-subunits, as well as MHC class I and II glycoproteins formed
      supramolecular receptor clusters in lipid rafts of the T lymphoma line Kit 225
      FT7.10. Fluorescence crosscorrelation microscopy demonstrated the comobility of
      IL-15R alpha with IL-2R alpha and MHC class I. A model was generated for subunit
      switching between IL-2R alpha and IL-15R alpha upon the binding of the
      appropriate cytokine resulting in the formation of high-affinity heterotrimeric
      receptors. This model suggests a direct role for the alpha-subunits, to which no
      definite function has been assigned so far, in tuning cellular responses to IL-2
      or IL-15. In addition, both alpha-chains were at least partially
      homodimerized/oligomerized, which could be the basis of distinct signaling
      pathways by the two cytokines.

PMID- 15263077
TI  - Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice.
AB  - Alzheimer's disease (AD) characteristically presents with early memory loss.
      Regulation of K(+) channels, calcium homeostasis, and protein kinase C (PKC)
      activation are molecular events that have been implicated during associative
      memory which are also altered or defective in AD. PKC is also involved in the
      processing of the amyloid precursor protein (APP), a central element in AD
      pathophysiology. In previous studies, we demonstrated that benzolactam (BL), a
      novel PKC activator, reversed K(+) channels defects and enhanced secretion of APP
      alpha in AD cells. In this study we present data showing that another PKC
      activator, bryostatin 1, at subnanomolar concentrations dramatically enhances the
      secretion of the alpha-secretase product sAPP alpha in fibroblasts from AD
      patients. We also show that BL significantly increased the amount of sAPP alpha
      and reduced A beta 40 in the brains of APP[V717I] transgenic mice. In a more
      recently developed AD double-transgenic mouse, bryostatin was effective in
      reducing both brain A beta 40 and A beta 42. In addition, bryostatin ameliorated
      the rate of premature death and improved behavioral outcomes. Collectively, these
      data corroborate PKC and its activation as a potentially important means of
      ameliorating AD pathophysiology and perhaps cognitive impairment, thus offering a
      promising target for drug development. Because bryostatin 1 is devoid of tumor
      promoting activity and is undergoing numerous clinical studies for cancer
      treatment in humans, it might be readily tested in patients as a potential
      therapeutic agent for Alzheimer's disease.

PMID- 15263078
TI  - MCM proteins and checkpoint kinases get together at the fork.

PMID- 15263079
TI  - Acetaminophen-induced hypothermia in mice is mediated by a prostaglandin
      endoperoxide synthase 1 gene-derived protein.
AB  - Acetaminophen is a widely used antipyretic analgesic, reducing fever caused by
      bacterial and viral infections and by clinical trauma such as cancer or stroke.
      In rare cases in humans, e.g., in febrile children or HIV or stroke patients,
      acetaminophen causes hypothermia while therapeutic blood levels of the drug are
      maintained. In C57/BL6 mice, acetaminophen caused hypothermia that was dose
      related and maximum (>2 degrees C below normal) with a dose of 300 mg/kg. The
      reduction and recovery of body temperature was paralleled by a fall of >90% and a
      subsequent rise of prostaglandin (PG)E(2) concentrations in the brain. In
      cyclooxygenase (COX)-2(-/-) mice, acetaminophen (300 mg/kg) produced hypothermia
      accompanied by a reduction in brain PGE(2) levels, whereas in COX-1(-/-) mice,
      the hypothermia to this dose of acetaminophen was attenuated. The brains of COX
      1(-/-) mice had approximately 70% lower levels of PGE(2) than those of WT
      animals, and these levels were not reduced further by acetaminophen. The putative
      selective COX-3 inhibitors antipyrine and aminopyrine also reduced basal body
      temperature and brain PGE(2) levels in normal mice. We propose that acetaminophen
      is a selective inhibitor of a COX-1 variant and this enzyme is involved in the
      continual synthesis of PGE(2) that maintains a normal body temperature. Thus,
      acetaminophen reduces basal body temperature below normal in mice most likely by
      inhibiting COX-3.

PMID- 15263080
TI  - Living longer: Information revolution, population expansion, and modern human
      origins.

PMID- 15263081
TI  - Global organization of terrestrial plant-nutrient interactions.

PMID- 15263082
TI  - Biography of David Tilman.

PMID- 15263083
TI  - Selective inhibition of the citrate-to-isocitrate reaction of cytosolic aconitase
      by phosphomimetic mutation of serine-711.
AB  - Iron-regulatory protein 1 (IRP1) is a dual-function protein with mutually
      exclusive roles as a posttranscriptional regulator of animal-cell iron metabolism
      or as the cytosolic isoform of the iron-sulfur enzyme aconitase (c-acon). Much
      effort has focused on the role of IRP1 in posttranscriptional gene regulation and
      in factors that influence its interconversion with c-acon, but little is known
      about the metabolic function and regulation of c-acon. The role of PKC-dependent
      phosphorylation of S711 on IRP1/c-acon function was examined. Phosphorylation
      state-specific antibodies revealed that S711 is phosphorylated by PKC in vitro
      and in human embryonic kidney cells treated with a PKC activator. In aco1 yeast,
      the phosphomimetic mutants S711D and S711E exhibited severely impaired aconitase
      function, whereas S711A and S711T were unaffected relative to the WT protein.
      Aconitase activity in yeast extracts displayed a similar pattern when assayed for
      capacity to convert citrate to isocitrate: WT, S711A, and S711T were active, but
      S711D and S711E activity was undetectable. In contrast, when measured by the
      conversion of isocitrate to cis-aconitate, S711D and S711E displayed substantial
      activity, indicating that phosphorylation impairs the citrate but not isocitrate
      mode of aconitase function. This possibility was confirmed in vivo by
      demonstrating that S711D and S711E specifically antagonized the requirement for
      isocitrate in two metabolic scenarios. Iron-responsive element RNA-binding
      affinity was unaffected by S711 mutations. Our results show that S711 is a target
      of phosphorylation capable of conferring distinct effects on c-acon function
      potentially dictating changes in cytosolic citrate/isocitrate metabolism.

PMID- 15263084
TI  - Cooperative action of coherent groups in broadly heterogeneous populations of
      interacting chemical oscillators.
AB  - We present laboratory experiments on the effects of global coupling in a
      population of electrochemical oscillators with a multimodal frequency
      distribution. The experiments show that complex collective signals are generated
      by this system through spontaneous emergence and joint operation of coherently
      acting groups representing hierarchically organized resonant clusters. Numerical
      simulations support these experimental findings. Our results suggest that some
      forms of internal self-organization, characteristic for complex multiagent
      systems, are already possible in simple chemical systems.

PMID- 15263085
TI  - Discovery and characterization of sialic acid O-acetylation in group B
      Streptococcus.
AB  - Group B Streptococcus (GBS) is the leading cause of human neonatal sepsis and
      meningitis. The GBS capsular polysaccharide is a major virulence factor and the
      active principle of vaccines in phase II trials. All GBS capsules have a terminal
      alpha 2-3-linked sialic acid [N-acetylneuraminic acid (Neu5Ac)], which interferes
      with complement-mediated killing. We show here that some of the Neu5Ac residues
      of the GBS type III capsule are O-acetylated at carbon position 7, 8, or 9, a
      major modification evidently missed in previous studies. Data are consistent with
      initial O-acetylation at position 7, and subsequent migration of the O-acetyl
      ester at positions 8 and 9. O-acetylation was also present on several other GBS
      serotypes (Ia, Ib, II, V, and VI). Deletion of the CMP-Neu5Ac synthase gene neuA
      by precise, in-frame allelic replacement gave intracellular accumulation of O
      acetylated Neu5Ac, whereas overexpression markedly decreased O-acetylation. Given
      the known GBS Neu5Ac biosynthesis pathway, these data indicate that O-acetylation
      occurs on free Neu5Ac, competing with the CMP-Neu5Ac synthase. O-acetylation
      often generates immunogenic epitopes on bacterial capsular polysaccharides and
      can modulate human alternate pathway complement activation. Thus, our discovery
      has important implications for GBS pathogenicity, immunogenicity, and vaccine
      design.

PMID- 15263086
TI  - Testosterone activates mitogen-activated protein kinase and the cAMP response
      element binding protein transcription factor in Sertoli cells.
AB  - The androgen testosterone is essential for the Sertoli cell to support the
      maturation of male germ cells and the production of spermatozoa
      (spermatogenesis). In the classical view of androgen action, binding of androgen
      to the intracellular androgen receptor (AR) produces a conformational change in
      AR such that the receptor-steroid complex has high affinity for specific DNA
      regulatory elements and is able to stimulate gene transcription. Here, we
      demonstrate that testosterone can act by means of an alternative, rapid, and
      sustainable mechanism in Sertoli cells that is independent of AR-DNA
      interactions. Specifically, the addition of physiological levels of testosterone
      to Sertoli cells stimulates the mitogen-activated protein kinase signaling
      pathway and causes phosphorylation of the cAMP response element binding protein
      transcription factor on serine 133, a modification known to be required for
      Sertoli cells to support spermatogenesis. Androgen-mediated activation of mitogen
      activated protein kinase and cAMP response element binding protein occurs within
      1 min, extends for at least 12 h and requires AR. Furthermore, androgen induces
      endogenous cAMP response element binding protein-mediated transcription in
      Sertoli cells. These newly identified mechanisms of androgen action in Sertoli
      cells suggest new targets for developing male contraceptive agents.

PMID- 15263087
TI  - Small-molecule-based identification of dynamic assembly of E2F-pocket protein
      histone deacetylase complex for telomerase regulation in human cells.
AB  - Activation of telomerase is crucial for cells to gain immortality. Most normal
      human somatic cells have a limited proliferative life span, and expression of the
      rate-limiting telomerase catalytic subunit, known as human telomerase reverse
      transcriptase (hTERT), has been believed to be tightly repressed. This model of
      hTERT regulation is challenged by the recent identification of the induction of
      hTERT in normal cycling human fibroblasts during their transit through S phase.
      Here we show the small-molecule-based identification of the assembly and
      disassembly of E2F-pocket protein-histone deacetylase (HDAC) complex as a key
      mechanistic basis for the repression and activation of hTERT in normal human
      cells. A cell-based chemical screen was used to identify a small molecule,
      CGK1026, that derepresses hTERT expression. CGK1026 inhibits the recruitment of
      HDAC into E2F-pocket protein complexes assembled on the hTERT promoter. Chromatin
      immunoprecipitation analysis reveals dynamic alterations in hTERT promoter
      occupancy by E2F and pocket proteins according to the cell cycle-dependent
      regulation of hTERT. Dominant-negative or protein-knockout strategies to disrupt
      the assembly of E2F-pocket protein-HDAC complex derepress hTERT and telomerase
      activity. Taken together with the results on the regulatory function of these
      complexes in cellular senescence and tumorigenesis, our findings suggest that
      dynamic assembly of E2F-pocket protein-HDAC complex plays a central role in the
      regulation of hTERT in a variety of proliferative conditions (e.g., normal
      cycling, senescent, and tumor cells).

PMID- 15263088
TI  - Evidence for defective energy homeostasis in amyotrophic lateral sclerosis:
      benefit of a high-energy diet in a transgenic mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      characterized by selective loss of motor neurons and progressive muscle wasting.
      Growing evidence indicates that mitochondrial dysfunction, not only occurring in
      motor neurons but also in skeletal muscle, may play a crucial role in the
      pathogenesis. In this regard, the life expectancy of the ALS G93A mouse line is
      extended by creatine, an intracellular energy shuttle that ameliorates muscle
      function. Moreover, a population of patients with sporadic ALS exhibits a
      generalized hypermetabolic state of as yet unknown origin. Altogether, these
      findings led us to explore whether alterations in energy homeostasis may
      contribute to the disease process. Here, we show important variations in a number
      of metabolic indicators in transgenic ALS mice, which in all shows a metabolic
      deficit. These alterations were accompanied early in the asymptomatic phase of
      the disease by reduced adipose tissue accumulation, increased energy expenditure,
      and concomitant skeletal muscle hypermetabolism. Compensating this energetic
      imbalance with a highly energetic diet extended mean survival by 20%. In
      conclusion, we suggest that hypermetabolism, mainly of muscular origin, may
      represent by itself an additional driven force involved in increasing motor
      neuron vulnerability.

PMID- 15263090
TI  - Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin
      responsiveness in the bone marrow but not in the liver environment.
AB  - IL-7 and thymic stromal lymphopoietin (TSLP) are two major cytokines controlling
      murine B cell development. IL-7 has been studied extensively, but only recently
      has it become possible to unravel the role of TSLP in detail. We studied the
      biological activities of TSLP in B cell development at distinct ages in the
      mouse. On the one hand, TSLP is able to give rise to a measurable B1 cell
      compartment derived from fetal liver pro-B cells, although, as is the case for B2
      cells, it does not play a prevalent role in the development of this subset. On
      the other hand, TSLP drives the proliferation of pro-B cells from the fetal and
      neonatal liver, but in the bone marrow environment, B cell precursors require pre
      B cell receptor expression for TSLP responsiveness.

PMID- 15263089
TI  - Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp.
      atroseptica and characterization of virulence factors.
AB  - The bacterial family Enterobacteriaceae is notable for its well studied human
      pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp.
      However, it also contains several plant pathogens. We report the genome sequence
      of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica
      (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato
      diseases. Approximately 33% of Eca genes are not shared with sequenced
      enterobacterial human pathogens, including some predicted to facilitate
      unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This
      proportion of genes also contains an overrepresentation of pathogenicity
      determinants, including possible horizontally acquired gene clusters for putative
      type IV secretion and polyketide phytotoxin synthesis. To investigate whether
      these gene clusters play a role in the disease process, an arrayed set of
      insertional mutants was generated, and mutations were identified. Plant bioassays
      showed that these mutants were significantly reduced in virulence, demonstrating
      both the presence of novel pathogenicity determinants in Eca, and the impact of
      functional genomics in expanding our understanding of phytopathogenicity in the
      Enterobacteriaceae.

PMID- 15263091
TI  - Genetic organization of the psbAD region in phages infecting marine Synechococcus
      strains.
AB  - The discovery of the genes psbA and psbD, encoding the D1 and D2 core components
      of the photosynthetic reaction center PSII (photosystem II), in the genome of the
      bacteriophage S-PM2 (a cyanomyovirus) that infects marine cyanobacteria begs the
      question as to how these genes were acquired. In an attempt to answer this
      question, it was established that the occurrence of the genes is widespread among
      marine cyanomyovirus isolates and may even extend to podoviruses. The phage psbA
      genes fall into a clade that includes the psbA genes from their potential
      Synechococcus and Prochlorococcus hosts, and thus, this phylogenetic analysis
      provides evidence to support the idea of the acquisition of these genes by
      horizontal gene transfer from their cyanobacterial hosts. However, the phage psbA
      genes form distinct subclades within this lineage, which suggests that their
      acquisition was not very recent. The psbA genes of two phages contain identical
      212-bp insertions that exhibit all of the canonical structural features of a
      group I self-splicing intron. The different patterns of genetic organization of
      the psbAD region are consistent with the idea that the psbA and psbD genes were
      acquired more than once by cyanomyoviruses and that their horizontal transfer
      between phages via a common phage gene pool, as part of mobile genetic modules,
      may be a continuing process. In addition, genes were discovered encoding a high
      light inducible protein and a putative key enzyme of dark metabolism,
      transaldolase, extending the areas of host-cell metabolism that may be affected
      by phage infection.

PMID- 15263093
TI  - Density functional theory study of adamantanediyl dications C10H142+ and protio
      adamantyl dications C10H162+.
AB  - Structures of the isomeric adamantanediyl dications C(10)H(14)(2+) and protio-1-
      and protio-2-adamantyl dications C(10)H(16)(2+) were investigated by using the
      density functional theory (DFT) method at the B3LYP/6-31G** level. Four
      structures, 1 b-e, were found to be minima on the potential energy surface of
      C(10)H(14)(2+). The 1,3-adamantanediyl dication 1b with two bridgehead tertiary
      carbocationic centers was found to be the most stable structure. On the potential
      energy surface of C(10)H(16)(2+) (protonated adamantly cation), five structures,
      2 b-f, were found to be minima. Each of the structure contains a two-electron,
      three-center bond. The C-C protonated 1-adamantyl dication, 2f, was characterized
      as the most stable structure. (13)C NMR chemical shifts of the structures were
      also calculated by using gauge-including atomic orbital-density functional theory
      and gauge-including atomic orbital-self-consistent field methods.

PMID- 15263094
TI  - VLA-4 integrin concentrates at the peripheral supramolecular activation complex
      of the immune synapse and drives T helper 1 responses.
AB  - The integrin alpha 4 beta 1 (VLA-4) not only mediates the adhesion and
      transendothelial migration of leukocytes, but also provides costimulatory signals
      that contribute to the activation of T lymphocytes. However, the behavior of
      alpha 4 beta 1 during the formation of the immune synapse is currently unknown.
      Here, we show that alpha 4 beta 1 is recruited to both human and murine antigen
      dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or
      a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular
      activation complex. However, when conjugates are formed in the presence of anti
      alpha 4 antibodies, VLA-4 colocalizes with the CD3-zeta chain at the center of
      the synapse. In addition, antibody engagement of alpha 4 integrin promotes
      polarization toward a T helper 1 (Th1) response in human in vitro models of
      CD4(+) T cell differentiation and naive T cell priming by dendritic cells. The in
      vivo administration of anti-alpha 4 integrin antibodies also induces an immune
      deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown
      Norway rats. These data reveal a regulatory role of alpha 4 integrins on T
      lymphocyte-antigen presenting cell cognate immune interactions.

PMID- 15263092
TI  - Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression.
AB  - Polyunsaturated fatty acids (PUFA) are essential structural components of the
      central nervous system. Their role in controlling learning and memory has been
      well documented. A nutrigenomic approach with high-density microarrays was used
      to reveal brain gene-expression changes in response to different PUFA-enriched
      diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes
      with altered expressions included transthyretin, alpha-synuclein, and
      calmodulins, which play important roles in synaptic plasticity and learning. The
      effect of perinatal omega-3 PUFA supply on gene expression later in life also was
      studied. Several genes showed similar changes in expression in rats fed omega-3
      deficient diets in the perinatal period, regardless of whether they or their
      mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this
      experiment, among the down-regulated genes were a kainate glutamate receptor and
      a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like
      factor, a tumor necrosis factor receptor, and cytochrome c. The possible
      involvement of the genes with altered expression attributable to different diets
      in different brain regions in young and aged rats and the possible mode of
      regulatory action of PUFA also are discussed. We conclude that PUFA-enriched
      diets lead to significant changes in expression of several genes in the central
      nervous tissue, and these effects appear to be mainly independent of their
      effects on membrane composition. The direct effects of PUFA on transcriptional
      modulators, the downstream developmentally and tissue-specifically activated
      elements might be one of the clues to understanding the beneficial effects of the
      omega-3 PUFA on the nervous system.

PMID- 15263095
TI  - Resistant tissues of modern marchantioid liverworts resemble enigmatic Early
      Paleozoic microfossils.
AB  - Absence of a substantial pretracheophyte fossil record for bryophytes (otherwise
      predicted by molecular systematics) poses a major problem in our understanding of
      earliest land-plant structure. In contrast, there exist enigmatic Cambrian
      Devonian microfossils (aggregations of tubes or sheets of cells or possibly a
      combination of both) controversially interpreted as an extinct group of early
      land plants known as nematophytes. We used an innovative approach to explore
      these issues: comparison of tube and cell-sheet microfossils with experimentally
      degraded modern liverworts as analogues of ancient early land plants. Lower
      epidermal surface tissues, including rhizoids, of Marchantia polymorpha and
      Conocephalum conicum were resistant to breakdown after rotting for extended
      periods or high-temperature acid treatment (acetolysis), suggesting fossilization
      potential. Cell-sheet and rhizoid remains occurred separately or together
      depending on the degree of body degradation. Rhizoid break-off at the lower
      epidermal surface left rimmed pores at the centers of cell rosettes; these were
      similar in structure, diameter, and distribution to pores characterizing
      nematophyte cell-sheet microfossils known as Cosmochlaina. The range of
      Marchantia rhizoid diameters overlapped that of Cosmochlaina pores. Approximately
      14% of dry biomass of Marchantia vegetative thalli and 40% of gametangiophores
      was resistant to acetolysis. Pre- and posttreatment cell-wall autofluorescence
      suggested the presence of phenolic compounds that likely protect lower epidermal
      tissues from soil microbe attack and provide dimensional stability to
      gametangiophores. Our results suggest that at least some microfossils identified
      as nematophytes may be the remains of early marchantioid liverworts similar in
      some ways to modern Marchantia and Conocephalum.

PMID- 15263096
TI  - Recapitulation of B cell differentiation in the central nervous system of
      patients with multiple sclerosis.
AB  - Clonally expanded populations of B cells carrying somatic mutations of Ig
      variable (V) region genes have been detected in the CNS of subjects with multiple
      sclerosis (MS), suggesting that a process of B cell affinity maturation with
      ensuing production of potentially pathogenic autoantibodies may occur inside the
      CNS. Here, we have characterized the B cell subsets present in the cerebrospinal
      fluid (CSF) of MS patients and of individuals with other inflammatory
      neurological disorders by flow cytometry. CD19(+)CD38(high+)CD77(+), Ki67(+), Bcl
      2(-) centroblasts, i.e., a B cell subset found exclusively in secondary lymphoid
      organs, were detected in the CSF but not in paired peripheral blood from both
      patient groups. CD27(+)IgD(-) memory B cells, i.e., cells with hyper-mutated IgV
      genes, were significantly increased in the CSF vs. paired peripheral blood and
      displayed up-regulation of the CD80 and CD86 costimulatory molecules and of CC
      chemokine receptor (CCR) 1, CCR2, and CCR4 in both patient groups. Lymphotoxin
      alpha, CXC ligand (CXCL) 12, and CXCL13, key mediators of lymphoid neogenesis,
      were present in the CSF from patients with MS and other inflammatory neurological
      disorders and were expressed in MS brain tissue, with selective localization in
      the outer layer of the capillary vessel wall. In conclusion, this study suggests
      that a compartmentalized B cell response occurs within the CNS during an ongoing
      inflammatory reaction, through a recapitulation of all stages of B cell
      differentiation observed in secondary lymphoid organs. The presence of
      lymphotoxin-alpha, CXCL12, and CXCL13 in the CNS may provide favorable
      microenvironmental conditions for these events.

PMID- 15263097
TI  - Formation and characterization of an all-ferrous Rieske cluster and stabilization
      of the [2Fe-2S]0 core by protonation.
AB  - The all-ferrous Rieske cluster, [2Fe-2S](0), has been produced in solution and
      characterized by protein-film voltammetry and UV-visible, EPR, and Mossbauer
      spectroscopies. The [2Fe-2S](0) cluster, in the overexpressed soluble domain of
      the Rieske protein from the bovine cytochrome bc(1) complex, is formed at -0.73 V
      at pH 7. Therefore, at pH 7, the [2Fe-2S](1+/0) couple is 1.0 V below the [2Fe
      2S](2+/1+) couple. The two cluster-bound ferrous irons are both high spin (S =
      2), and they are coupled antiferromagnetically (-J > or = 30 cm(-1), H =-2JS1.S2)
      to give a diamagnetic (S = 0) ground state. The ability of the Rieske cluster to
      exist in three oxidation states (2+, 1+, and 0) without an accompanying coupled
      reaction, such as a conformational change or protonation, is highly unusual.
      However, uncoupled reduction to the [2Fe-2S](0) state occurs at pH > 9.8 only,
      and at high pH the intact cluster persists in solution for <1 min. At pH < 9.8,
      the all-ferrous cluster is stabilized significantly by protonation. A combination
      of experimental data and calculations based on density functional theory suggests
      strongly that the proton binds to one of the cluster mu(2)-sulfides, consistent
      with observations that reduced [3Fe-4S] clusters are protonated also. The
      implications for our understanding of coupled reactions at iron-sulfur clusters
      and of the factors that determine the relative stabilities of their different
      oxidation states are discussed.

PMID- 15263098
TI  - Late viral interference induced by transdominant Gag of an endogenous retrovirus.
AB  - The sheep genome harbors approximately 20 copies of endogenous retroviruses
      (enJSRVs) closely related to the exogenous and oncogenic Jaagsiekte sheep
      retrovirus (JSRV). One of the enJSRV loci, enJS56A1, has a defect for viral exit.
      We report a previously uncharacterized mechanism of retroviral interference. The
      defect possessed by enJS56A1 is determined by its Gag protein and is
      transdominant over the exogenous JSRV. By electron microscopy, cells transfected
      by enJS56A1, with or without JSRV, show agglomerates of tightly packed
      intracellular particles most abundant in the perinuclear area. The defect in exit
      and ability to interfere with JSRV exit could be largely attributed to the
      presence of tryptophan, rather than arginine, at position 21 of enJS56A1 Gag; C98
      and V102 also contribute to these properties. We found that enJS56A1 or similar
      loci containing W21, C98, and V102 are expressed in sheep endometrium. enJS56A1
      is a previously unrecognized example of a naturally occurring endogenous
      retrovirus expressing a dominant negative Gag acting at a late step of the viral
      replication cycle. Understanding the late blockade exerted by enJS56A1 could
      unravel fundamental aspects of retroviral biology and help to devise new
      antiretroviral strategies.

PMID- 15263099
TI  - Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches
      mitogen-activated protein kinase signaling to late endosomes.
AB  - Signaling pathways in eukaryotic cells are often controlled by the formation of
      specific signaling complexes, which are coordinated by scaffold and adaptor
      proteins. Elucidating their molecular architecture is essential to understand the
      spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight
      (K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen
      activated protein kinase (MAPK) signaling. Here, we present the 1.9-A crystal
      structure of a biologically functional p14/MP1 complex. The overall topology of
      the individual MP1 and p14 proteins is almost identical, having a central five
      stranded beta-sheet sandwiched between a two-helix and a one-helix layer.
      Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentation and
      yields a unique, almost symmetrical, complex with several potential protein
      binding sites on its surface. Mutational analysis allowed identification of the
      p14 endosomal adaptor motif, which seems to orient the complex relative to the
      endosomal membrane. Two highly conserved and hydrophobic protein-binding sites
      are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimer and
      might therefore function as docking sites for the target proteins extracellular
      regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence
      analyses revealed that MP1/p14, together with profilins, define a protein
      superfamily of small subcellular adaptor proteins, named ProflAP. Taken together,
      the presented work provides insight into the spatial regulation of MAPK
      signaling, illustrating how p14 and MP1 collaborate as an endosomal
      adaptor/scaffold complex.

PMID- 15263100
TI  - Effect of ceasing creatine supplementation while maintaining resistance training
      in older men.
AB  - The authors previously found that creatine (Cr) combined with 12 weeks of
      resistance training enhanced muscle strength and endurance and lean tissue mass
      (LTM) in older men. Their purpose in this study was to assess these variables
      with cessation of Cr combined with 12 weeks of reduced training (33% lower
      volume) in a subgroup of these men (n = 8, 73 years old) compared with 5 men (69
      years old) who did not receive Cr. Strength (1-repetition maximum [1-RM]),
      endurance (maximum number of repetitions over 3 sets at 70-80% 1-RM), and LTM
      (dual-energy X-ray absorptiometry) were assessed before and after 12 weeks of Cr
      cessation combined with reduced-volume training. No changes in strength or LTM
      occurred. Muscle endurance was significantly reduced (7-21%; p <.05), with the
      rate of change similar between groups. Withdrawal from Cr had no effect on the
      rate of strength, endurance, and loss of lean tissue mass with 12 weeks of
      reduced-volume training.

PMID- 15263103
TI  - Rinneite, K(3)Na[FeCl(6)], at 293, 84 and 9.5 K.
AB  - The crystal structure of tripotassium sodium hexachloroferrate(II) has been
      determined by X-ray diffraction at 293, 84 and 9.5 K. The accurate and extensive
      data sets collected should be suitable for charge-density analysis studies.

PMID- 15263101
TI  - Leadership in physical activity groups for older adults: a qualitative analysis.
AB  - The purpose of this study was to determine whether a theory-based framework could
      be used to deductively identify and understand the characteristics of
      motivational leaders of physical activity groups for older adults. Participants
      were 23 older adults (mean age = 78.5 +/- 8.0 years, 65% women). An interview
      guide approach was employed to elicit older adults' thoughts on important
      characteristics of physical activity group leaders. The data suggested that
      effective leaders are those whom the participants feel are properly qualified,
      are able to develop a personal bond with participants, and can use their
      knowledge and the group to demonstrate collective accomplishments. It was
      concluded that the findings could be used to extend the leadership activities
      beyond the traditional technical performance and individual feedback to include
      activities of social integration. Furthermore, the conceptual framework
      identified can serve as a valuable tool in guiding future researchers in their
      examination of leadership in physical activity groups for older adults.

PMID- 15263104
TI  - Magnesium sulfate hexahydrate at 120 K.
AB  - The structure of [Mg(H(2)O)(6)]SO(4) was redetermined at 120 K, confirming the
      hydrogen-bond pattern found at room temperature [Zalkin et al. (1964). Acta
      Cryst. 17, 235-240] but showing the librational corrections of bond lengths to be
      unrealistic.

PMID- 15263105
TI  - Potassium barium bismuth oxide.
AB  - KBa(4)Bi(3)O crystallizes in the centrosymmetric tetragonal space group I4/mcm.
      In this compound, bismuth is present as two anionic species, i.e. Bi(2)(4-)
      dumbbells [Bi-Bi 3.113 (3) A] and isolated Bi(3-). Atom Bi1 (Bi(3-)) lies inside
      a bicapped square antiprism (2 x K and 8 x Ba). Atom Bi2, which forms the Bi(2)(4
      ) dumbbell, sits inside a bicapped distorted trigonal prism (2 x K and 6 x Ba). O
      atoms occupy tetrahedral voids between Ba atoms.

PMID- 15263106
TI  - Four copper(II) complexes with potentially tetradentate tripodal ligands.
AB  - The four title Cu(II) compounds are chloro[(2-furylmethyl)bis(2
      pyridylmethyl)amine-N,N',N"]copper(II) perchlorate,
      [CuCl(C(17)H(17)N(3)O)]ClO(4), (I), chloro{2-[bis(2
      pyridylmethyl)amino]ethanolato-N,N',N",O}copper(II) hemi[tetrachlorocopper(II)],
      [CuCl(C(14)H(17)N(3)O)][CuCl(4)](1/2), (II), chloro[(2-morpholinoethyl)bis(2
      pyridylmethyl)amine-N,N',N",N"']copper(II) perchlorate,
      [CuCl(C(18)H(24)N(4)O)]ClO(4), (III), and chloro[(2-piperidinylethyl)bis(2
      pyridylmethyl)amine-N,N',N",N"']copper(II) hexafluorophosphate,
      [CuCl(C(19)H(26)N(4))]PF(6), (IV). They have tripodal potentially tetradentate
      ligands. In (I), the O atom of the furan moiety weakly coordinates to the Cu atom
      at a distance of 2.750 (3) A.

PMID- 15263107
TI  - Tribenzyl{eta(5)-[2-(p-tolyl)prop-2-yl]cyclopentadienyl}zirconium.
AB  - The title compound, [Zr(C(7)H(7))(3)(C(15)H(17))], (I), crystallizes from light
      petroleum with two independent molecules in the asymmetric unit. Whereas in the
      parent molecule, Zr(eta(5)-C(5)H(5))(CH(2)Ph)(3), all three Zr-CH(2)Ph angles are
      equal, in (I), they differ significantly. In spite of their different
      environments, both independent molecules in (I) exhibit a small, an expected, and
      a large Zr-CH(2)Ph angle. The angles are similar to those of the closely related
      tribenzyl[eta(5)-(benzyldimethylsilyl)cyclopentadienyl]zirconium complex. The
      smallest Zr-CH(2)Ph angle and the consequently relatively short Zr.C(ipso)
      distance are indicative of eta(2)-bonding of the benzyl group.

PMID- 15263108
TI  - Tris(1,10-phenanthroline-N,N')chromium(III) triperchlorate hydrate.
AB  - The structure of the cation in [Cr(C(12)H(8)N(2))(3)](ClO(4))(3).H(2)O consists
      of the Cr atom bonded to the N atoms of the three 1,10-phenanthroline (phen)
      ligands, resulting in a distorted octahedral arrangement with the six Cr-N
      distances ranging from 2.040 (4) to 2.055 (4) A. One of the perchlorate anions is
      disordered and is located around two special positions.

PMID- 15263109
TI  - micro-Terephthalato-bis[bis(1,10-phenanthroline)copper(I)] diperchlorate.
AB  - The title compound, [Cu(2)(C(8)H(4)O(4))(C(12)H(8)N(2))(4)](ClO(4))(2), was
      prepared from the hydrothermal reaction of CuCl(2), 1,4-dicyanobenzene, 1,10
      phenanthroline and water at 443 K. The compound is a dimer in which the cation
      lies about an inversion center. The terephthalate moiety acts as a bridging
      ligand and the phenanthrolines as terminal ligands. The unique Cu atom is
      coordinated by two O and four N atoms in a distorted octahedral geometry, with Cu
      O distances of 1.955 (2) and 2.815 (2) A, and Cu-N distances of 2.008 (2) to
      2.216 (2) A.

PMID- 15263110
TI  - cis-Bis(dicyanamido)bis(1,10-phenanthroline)manganese(II) and cis
      bis(dicyanamido)bis(1,10-phenanthroline)zinc(II).
AB  - The title compounds are isomorphous, comprised of neutral monomeric
      [M(phen)(2)(dca)(2)] [(I): M = Mn, (II): M = Zn; phen is 1,10-phenanthroline,
      C(12)H(8)N(2); dca is dicyanamide, C(2)N(3)] molecules. In the molecule, the
      divalent metal ion is in a distorted octahedral coordination environment formed
      by six N atoms from the phen and dca ligands. The Mn-N [2.144 (2)-2.319 (2) A]
      and Zn-N [2.075 (2)-2.245 (2) A] distances are in agreement with the difference
      in size of the two divalent ions.

PMID- 15263111
TI  - (o-Benzoquinone diimine-N,N')dichlorobis(triphenylphosphine-P)ruthenium(II) 1.33
      methanol 0.33-dichloromethane solvate.
AB  - The Ru atom in the title compound,
      [RuCl(2){P(C(6)H(5))(3)}(2){C(6)H(4)(NH)(2)}].1.33CH(3)OH.0.33CH(2)Cl(2), shows a
      six-coordinate octahedral geometry, with a trans arrangement of the
      triphenylphosphine groups. One and a half molecules of complex, two molecules of
      methanol and a half molecule of dichloromethane form the asymmetric unit, with
      crystallographic twofold rotation symmetry for the complex molecule in a special
      position.

PMID- 15263112
TI  - (Acetonitrile-N)(o-benzoquinone diimine-N,N')chloro-trans-bis(triphenylphosphine
      P)ruthenium(II) hexafluorophosphate 0.25-hydrate.
AB  - The Ru atom in the title compound,
      [RuCl(CH(3)CN){P(C(6)H(5))(3)}(2){C(6)H(4)(NH)(2)}]PF(6).0.25H(2)O, has a six
      coordinate octahedral geometry, with a trans arrangement of the
      triphenylphosphine groups. The asymmetric unit contains two complex molecules and
      a partially occupied water site. Principal dimensions include Ru-N 1.958 (4)
      2.044 (5), Ru-P 2.3897 (16)-2.4092 (15), and Ru-Cl 2.4280 (15) and 2.4295 (16) A

PMID- 15263113
TI  - Hexaaquacobalt(II) bis(4-toluenesulfonate).
AB  - The title compound, [Co(H(2)O)(6)](CH(3)C(6)H(4)SO(3))(2), has a structure where
      the metal atom is surrounded by six molecules of water forming the cation and the
      anion is deprotonated 4-toluenesulfonic acid. The Co atom is in a nearly regular
      octahedral coordination geometry, with Co-O distances between 2.0529 (14) and
      2.0810 (16) A, and angles ranging from 87.25 (9) to 92.75 (9) degrees. The
      supramolecular structure consists of parallel layers of cations and anions. The
      anions are arranged with their sulfonate groups directed towards the cation layer
      in an alternating fashion and form hydrogen bonds with the water molecules of the
      cation.

PMID- 15263114
TI  - Tricarbonyl[(6a,7,8,9,10a-eta)-3,3-dimethyl-3H-benzo[f]chromene]chromium.
AB  - The title compound, [Cr(C(15)H(14)O)(CO)(3)], is a chromene complexed with
      tricarbonylchromium and it exhibits photochromic properties. The molecular
      geometry is compared to that of two similar complexes. The analysis results
      indicate that complexation has minor effects on the chromene structure.

PMID- 15263115
TI  - Dysobinin, a tetranortriterpenoid.
AB  - The planar furan ring in the title compound (6beta-acetoxyazadirone,
      C(30)H(38)O(6)) is twisted with respect to the steroid D ring. The crystal
      structure is stabilized by C-H.O hydrogen bonds and van der Waals interactions.

PMID- 15263116
TI  - Two hydrochlorides of 7-methyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca
      1(17),13,15-triene.
AB  - The X-ray structure determinations of the two title compounds, namely 7-methyl
      7,17-diaza-3,11-diazoniabicyclo[11.3.1]heptadeca-1(17),13,15-triene dichloride
      monohydrate, C(14)H(26)N(4)(2+).2Cl(-).H(2)O, (I), and 7-methyl-17-aza-3,7,11
      triazoniabicyclo[11.3.1]heptadeca-1(17),13,15-triene 2.826-chloride 0.174
      nitrate, C(14)H(27)N(4)(3+).2.826Cl(-).0.174NO(3)(-), (II), are reported.
      Protonation occurs at the secondary amine N atoms in (I) and at all three amine N
      atoms in (II) to which the Cl(-) ions are linked via N-H.Cl hydrogen bonds. The
      macrocyclic hole is quite different in both structures, as is observed by
      comparing particularly the N3.N4 distances [2.976 (4) and 4.175 (4) A for (I) and
      (II), respectively]. In (II), a Cl(-) ion alternates with an NO(3)(-) ion in a
      disordered structure.

PMID- 15263117
TI  - Dimethylphenylsulfonium trifluoromethanesulfonate and methyldiphenylsulfonium
      trifluoromethanesulfonate.
AB  - The bonding geometry of sulfur in the cations of the title compounds,
      C(8)H(11)S(+).CF(3)SO(3)(-) and C(13)H(13)S(+).CF(3)SO(3)(-), respectively, is
      similar and is independent of the ratio of the Me/Ph substituents. As expected,
      in both cations, the S-Ph bonds are somewhat shorter than the S-Me bonds. In both
      crystal structures, the interaction between cations and anions is similar.

PMID- 15263118
TI  - [Tris(4-tolyl)methyl]benzene.
AB  - The crystal structure of the title compound, C(28)H(26), in the monoclinic space
      group C2/c has a columnar packing arrangement with a 7.20 A axis, a feature
      common to several tetraphenylmethanes.

PMID- 15263119
TI  - 1,3-Propanediammonium bis(3'-nitro-trans-cinnamate) and trans-1,2
      cyclohexanediammonium bis(3'-nitro-trans-cinnamate).
AB  - In the title two adducts, C(3)H(12)N(2)(2+).2C(9)H(6)NO(4)(-), (I), and
      C(6)H(16)N(2)(2+).2C(9)H(6)NO(4)(-), (II), hydrogen bonds between the diammonium
      and carboxylate ions form a two-dimensional network parallel to the ab plane in
      (I) and one-dimensional chains along the c axis in (II). The
      cyclohexanediammonium ion in (II) has a crystallographic twofold axis.

PMID- 15263121
TI  - Ferroelastic n-butylammonium dihydrogenphosphate.
AB  - Crystals of n-butylammonium dihydrogenphosphate, C(4)H(9)NH(3)(+).H(2)PO(4)(-),
      reveal ferroelasticity at room temperature and a number of phase transitions when
      heated up to approximately 373 K. Some of these phase transitions show hysteresis
      effects. All atoms except two H atoms exist in pairs linked by the lost symmetry
      operations derived from the prototypic space group P2/b2(1)/n2(1)/a. Each of
      these two different H atoms is involved in an asymmetric hydrogen bond between an
      oxygen pair. Ferroelastic switching is concomitant with jumps of these hydrogen
      species from donor to acceptor O atoms. The studied structure belongs to the
      structural family of n-hexyl- to n-decylammonium dihydrogenphosphates and differs
      by localization of alternating layers from n-propyl- and n-pentylammonium
      dihydrogenphosphates. The studied crystal was slightly twinned; the minor domain
      constituted approximately 2%.

PMID- 15263120
TI  - Tris(2-cyanoethyl)amine.
AB  - In the title compound, N(CH(2)CH(2)CN)(3), (I), the three cyanoethyl groups adopt
      a conformation with the CN groups oriented in the same direction, suggesting the
      compound may behave as a potential tripodal ligand.

PMID- 15263122
TI  - 3-Acetoxycyclohex-4-ene-1,2-dicarboxylic anhydride.
AB  - The title compound, C(10)H(10)O(5), was found to exist as the endo-cis isomer
      with a pair of enantiomers in the asymmetric unit. The cyclohexene ring is folded
      about the methylene-to-CH(acetoxy) vector to give a boat conformation.

PMID- 15263123
TI  - (R)-(+)-2,2'-Bis(diphenylphosphinoyl)-1,1'-binaphthyl.
AB  - The title compound, BINAP oxide, C(44)H(32)O(2)P(2), (I), was synthesized by
      direct oxidation of (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)
      with tert-butyl hydroperoxide in toluene solution. The angle between the naphthyl
      planes of the binaphthyl group is 94.17 (3) degrees.

PMID- 15263124
TI  - 1-(2-Hydroxy-4,6-dimethylphenyl)ethanone.
AB  - In the crystal of the title compound, C(10)H(12)O(2), there are two symmetry
      independent molecules, which are essentially superimposable. Each molecule
      exhibits an intramolecular O-H.O hydrogen bond, with O.O separations of 2.483 (4)
      and 2.468 (4) A.

PMID- 15263125
TI  - 3,5-Difluoro-4-nitropyridine N-oxide and 3,5-diamino-4-nitropyridine N-oxide
      monohydrate.
AB  - The molecule of 3,5-difluoro-4-nitropyridine N-oxide, C(5)H(2)F(2)N(2)O(3), is
      twisted around the C-NO(2) bond by 38.5 (1) degrees, while the 3,5-diamino
      analogue, 3,5-diamino-4-nitropyridine N-oxide monohydrate,
      C(5)H(6)N(4)O(3).H(2)O, adopts a planar conformation stabilized by intramolecular
      hydrogen bonds, with a significant redistribution of pi electrons.

PMID- 15263126
TI  - Diethyl 9,10-dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylate.
AB  - The title compound, C(22)H(22)O(4), is the product of the Diels-Alder reaction of
      anthracene with fumaric acid diethyl ester. The molecular C(2) symmetry is nearly
      fulfilled in the crystal. Only the terminal torsion angles about the O-CH(2)
      groups show significant differences.

PMID- 15263127
TI  - Dichloromaleic anhydride.
AB  - Although molecules of the title compound, 3,4-dichloro-2,5-dihydrofuran-2,5-dione
      (dichloromaleic anhydride, C(4)Cl(2)O(3)), (I), possess approximate non
      crystallographic C(2v) symmetry, the two chlorine substituents deviate from the
      ring plane. Their deviations are in the same direction, but with values of 0.0356
      (17) and 0.0167 (17) A, they differ significantly in magnitude. The closest
      intermolecular contact is of 2.888 (2) A between a carbonyl O atom and the C atom
      of a carbonyl group, with the O.C direction orthogonal to the C=O bond
      [O5.C2(i)=O2(i) 93.6 (2) degrees; symmetry code: (i) $3 ?over 2$ - x, -(1/2) + y,
      z]. These contacts form infinite chains of molecules running parallel to the
      crystallographic b direction.

PMID- 15263128
TI  - Pyridine-4-carbaldehyde azine.
AB  - In the crystal structure of the title compound, C(12)H(10)N(4), the pyridine ring
      makes a dihedral angle of 1.12 (9) degrees with the mean plane of the complete
      almost planar and crystallographically centrosymmetric molecule. There are stacks
      of parallel molecules along the a-axis direction, with alternate stacks having a
      herring-bone arrangement relative to each other and an interplanar spacing of
      3.551 A.

PMID- 15263129
TI  - 3-Acetyl-4-benzoyl-2-methyl-5-phenyl-3,3a-dihydropyrazolo[2,3-c]pyrimidine-7(6H)
      thione.
AB  - The molecule of the title compound, C(22)H(19)N(3)O(2)S, is not planar. The
      dihedral angle between the two phenyl rings is 27.46 (7) degrees and in the
      dihydropyrazolopyrimidine ring the total puckering amplitude Q(T) is 0.526 (3) A.
      The structure is stabilized by both intra- and intermolecular C-H.O interaction,
      and by an intermolecular N-H.S hydrogen bond.

PMID- 15263130
TI  - Disodium chromium(III) hexamolybdoiodate(VII) 24-hydrate,
      Na(2)Cr[IMo(6)O(24)].24H(2)O.
AB  - The title compound can be formulated as
      [Cr(H(2)O)(6)][Na(2)(H(2)O)(10)][IMo(6)O(24)].8H(2)O. The anion has the I atom on
      an inversion centre and has close to $?overline 3$m symmetry, with I-O bond
      lengths in the range 1.881-1.890 (2) A and Mo-O bond lengths in the ranges 1.697
      (3)-1.714 (3), 1.915 (2)-1.948 (2) and 2.317 (2)-2.357 (2) A.

PMID- 15263131
TI  - micro-Oxo-bis{{2,2'-[2,2-dimethylpropane-1,3
      diylbis(nitrilomethylidyne)]diphenolato}oxorhenium(V)}
AB  - The title compound, [Re(2)O(3)(C(19)H(20)N(2)O(2))(2)], is a hexacoordinate
      complex containing an [Re(2)O(3)](4+) core with a linear O=Re-O-Re=O bridge. The
      distorted octahedral coordination of the Re(V) atom is achieved by an N(2)O(2)
      donor set from the tetradentate imine-phenol ligand. The overall charge of the
      compound is neutral due to deprotonation of the phenol groups, and the
      terminating and bridging O atoms. The Re=O and Re-O bond distances of the
      [Re(2)O(3)](4+) core are 1.699 (4) and 1.911 (1) A, respectively. The Re-O and Re
      N bond distances of the equatorial plane are in the ranges 2.024 (4)-2.013 (4)
      and 2.128 (5)-2.120 (5) A, respectively.

PMID- 15263132
TI  - An N-unprotected Fischer pyrrolidinylidene complex.
AB  - The synthesis and crystal structure of pentacarbonyl(pyrrolidin-2
      ylidene)chromium(0), [Cr(C(4)H(7)N)(CO)(5)], is reported. The compound shows
      strong interaction between the lone pair at nitrogen and the carbene C atom, and
      weak intermolecular hydrogen bonds.

PMID- 15263133
TI  - catena-Poly[fac-trichloromethyltin(IV)-micro-[meso-1,2-bis(phenylsulfinyl)ethane
      O:O']].
AB  - In the title compound, [SnCl(3)(CH(3))(C(6)H(5)SOCH(2))(2)](n), the octahedral
      Sn(IV) centres are bridged by meso-1,2-bis(phenylsulfinyl)ethane ligands forming
      infinite chains along the [100] direction.

PMID- 15263134
TI  - Bis(triethanolamine-O,O')nickel(II) diacetate.
AB  - The title compound, [Ni{N(CH(2)CH(2)OH)(3)}(2)](CH(3)COO)(2), was prepared and
      the structure determined. It is isostructural with the copper(II) analogue.

PMID- 15263135
TI  - (p-Nitrobenzoato)triphenyltin at 298 K.
AB  - The structure at 298 K described here, [Sn(C(6)H(5))(3)(C(7)H(4)NO(4))],
      completely confirms the results at 173 K obtained previously [Weng, Das &
      Robinson (1990), Malays. J. Sci. 12, 57]. In both structures, weak interaction
      between Sn and the carbonyl O atom of the benzoate group provides a distorted
      trigonal-pyramidal environment at the Sn atom derived from its pseudo-tetrahedral
      primary coordination in both molecules of the asymmetric unit.

PMID- 15263136
TI  - Pentacarbonyl(di-2-pyridylamine)tungsten(0).
AB  - In the title molecular complex, (I), the W atom is in an octahedral environment
      with four equatorial carbonyl ligands and a fifth in an axial position trans to
      the monodentate dipyridylamine ligand. The long dimension of this last bisects
      the angle between two of the equatorial carbonyl groups and while the non-bonded
      pyridyl N atom is directed away from the W atom, the bridging amine group is
      directed towards it. Thus, in addition to the N atom to which it is attached, the
      amino H has two nearest neighbour C atoms of equatorial carbonyl groups but does
      not participate in hydrogen bonding in any real or usual sense. The W-C bond
      distance for the axial carbonyl group is notably less than those of the
      equatorial groups.

PMID- 15263137
TI  - Bis(1-acetonylpyridinium) pyridinium hexaiodobismuth(III).
AB  - The crystal structure of the title complex, (C(8)H(10)N)(2)(C(5)H(6)N)[BiI(6)],
      contains discrete [BiI(6)](3-) anions, and (HNC(5)H(5))(+) and
      (CH(3)COCH(2)NC(5)H(5))(+) cations separated by normal van der Waals contacts.
      The [BiI(6)](3-) anion has the Bi atom on an inversion centre. The
      (HNC(5)H(5))(+) cation also lies about an inversion centre and is disordered. The
      (CH(3)COCH(2)NC(5)H(5))(+) cation lies in a general position.

PMID- 15263138
TI  - Bis[bis(N,N-diethyl-1,1-diselenocarbamato)copper(II)], [Cu(Se(2)CNEt(2))(2)](2).
AB  - The title centrosymmetric Cu(II) binuclear complex, bis(micro-N,N-diethyl-1,1
      diselenocarbamato-Se,Se':Se)bis[(N,N-diethyl-1,1-diselenocarbamato
      Se,Se')copper(II)], [Cu(Se(2)CNEt(2))(2)](2) or [Cu(2)(C(5)H(10)NSe(2))(4)], is
      built from two symmetry-related [Cu{Se(2)CN(Et)(2)}(2)] units by pairs of Cu-Se
      bonds. The coordination geometry at the unique Cu atom is distorted square
      pyramidal, with Cu-Se distances in the range 2.4091 (11)-2.9095 (10) A.

PMID- 15263139
TI  - [1,2-Diphenyl-N,N'-bis(salicylidene)-(RR,SS)-1,2
      ethanediyldiaminato]nitridomanganese(V).
AB  - The title compound, [MnN(C(28)H(22)N(2)O(2))], has a distorted square-pyramidal
      coordination with an Mn[triple-bond]N bond length of 1.516 (2) A at the apical
      position. The five-membered chelate ring adopts a gauche conformation with the
      two phenyl groups in equatorial orientations.

PMID- 15263140
TI  - The exo and endo isomers of [N,N'-bis(salicylidene)-1,2-diphenyl-(RS,SR)-1,2
      ethanediyldiaminato]oxovanadium(IV).
AB  - The title complexes, exo- and endo-[VO(C(28)H(22)N(2)O(2))], show monomeric
      structures with a distorted square-pyramidal coordination. The two phenyl groups
      on the five-membered N,N'-chelate ring are both on the same side as the oxo
      ligand for the exo isomer and on opposite sides for the endo isomer.

PMID- 15263141
TI  - exo-[N,N'-Bis(3-tert-butylsalicylidene)-1,2-diphenyl-(RS,SR)-1,2
      ethanediyldiaminato]oxovanadium(IV).
AB  - The title mononuclear oxovanadium(IV) complex, [VO(C(36)H(38)N(2)O(2))], has a
      distorted square-pyramidal coordination. The complex was shown to be the exo
      isomer.

PMID- 15263142
TI  - Tris(1,10-phenanthroline-N,N')iron(II) dithiocyanate trihydrate.
AB  - The title mononuclear iron(II) complex, [Fe(C(12)H(8)N(2))(3)](NCS)(2).3H(2)O,
      has a slightly distorted octahedral coordination. One of the thiocyanate ions and
      one of the water molecules of crystallization show positional disorder.

PMID- 15263143
TI  - Tetra-micro-acetato-O:O'-bis[(7-azaindole-N)copper(II)].
AB  - The title complex, [Cu(2)(C(2)H(3)O(2))(4)(C(7)H(6)N(2))(2)], shows a binuclear
      cage structure having an inversion centre. There are intramolecular N-H.O
      hydrogen bonds between the 7-azaindole ligands and the bridging acetate O atoms.

PMID- 15263144
TI  - micro-Acetato-O:O'-bis{[bis(salicylidene)ethylenediaminato]manganese(III)}
      perchlorate.
AB  - In the title complex, [Mn(2)(C(16)H(14)N(2)O(2))(2)(C(2)H(3)O(2))]ClO(4), two
      [Mn(salen)] moieties [salen is bis(salicylidene)ethylenediamine] are connected
      through a micro-acetate bridge in a syn-anti fashion. The Mn.Mn distance is 5.365
      (1) A.

PMID- 15263145
TI  - micro-Chloro-bis{[benzylbis(2-pyridylmethyl)amine-kappa(3)N]chlorocopper(II)}
      perchlorate hemihydrate.
AB  - In the title dinuclear Cu(II) compound,
      [Cu(2)Cl(3)(C(19)H(19)N(3))(3)]ClO(4).0.5H(2)O, the coordination geometry around
      the Cu atoms is square pyramidal, with the bridging Cl atom at the apical
      positions. The Cu-Cl-Cu angle is 136.9 (1) degrees and the Cu.Cu distance is
      4.961 (1) A.

PMID- 15263146
TI  - [N'-Benzoyl-N,N-bis(2-pyridylmethyl-kappaN)ethylenediamine
      kappaN]chlorocopper(II) hexafluorophosphate.
AB  - The title mononuclear copper(II) complex, [CuCl(C(21)H(22)N(4)O)]PF(6), shows a
      distorted square-planar coordination and the benzoylamino N atom does not
      coordinate to the Cu atom.

PMID- 15263147
TI  - [1,6-Bis(2-pyridylmethyl)-2,5-diazahexane-kappa(4)N]chlorocopper(II) perchlorate.
AB  - The title mononuclear copper(II) compound, [CuCl(C(16)H(22)N(4))]ClO(4), shows a
      slightly tetrahedrally distorted square-pyramidal coordination with the chlorine
      ligand at the apical position. The directions of the two N-Me bond axes are syn
      to the Cu-Cl bond.

PMID- 15263148
TI  - Chloro[N',N'-diethyl-N,N-bis(2-pyridylmethyl)ethylenediamine-kappa(4)N]copper(II)
      perchlorate.
AB  - The title mononuclear copper(II) complex, [CuCl(C(18)H(26)N(4))]ClO(4), shows a
      square-pyramidal coordination with the diethylamino N atom at the apical
      position. Large anisotropies in the displacement parameters of the non-H atoms of
      the ligand seem to be due to rotational disorder of the ClO(4)(-) anion.

PMID- 15263149
TI  - [N,N'-Bis(3-carboxysalicylidene)-1,2-diphenyl-(RR,SS)-1,2-ethanediyldiaminato
      O,N,N',O'](methanol-O)oxovanadium(IV) and [N,N'-bis(3-carboxysalicylidene)-2,3
      dimethyl-2,3-butanediyldiaminato-O,N,N',O']oxovanadium(IV) monohydrate.
AB  - The two title mononuclear oxovanadium (IV) complexes,
      [VO(C(30)H(22)N(2)O(6))(CH(3)OH)] and [VO(C(22)H(22)N(2)O(6))].H(2)O,
      respectively, have distorted square-pyramidal coordination and the 3-carboxy
      groups form intramolecular hydrogen bonds with the coordinated salicyl O atoms.
      In (I), methanol coordinates to the vanadium atom trans with respect to the oxo
      ligand.

PMID- 15263150
TI  - Redetermination of bis{[(2-hydroxyphenylmethyl)bis(2
      pyridylmethyl)aminato]copper(II)} diperchlorate.
AB  - The structure of the title compound, [Cu(2)(C(19)H(18)N(3)O)(2)](ClO(4))(2), was
      reported with insufficient accuracy because of a twinning problem by Adams,
      Bailey, Campbell, Fenton & He [J. Chem. Soc. Dalton Trans. (1996), pp. 2233
      2237]. The dinuclear phenolate-bridged Cu(II) complex has an inversion centre.

PMID- 15263151
TI  - Ethylammonium and diethylammonium salts of chloranilic acid.
AB  - In the crystals of two title salts of chloranilic acid (2,5-dichloro-3,6
      dihydroxy-p-benzoquinone), namely ethylammonium chloranilate,
      C(2)H(8)N(+).C(6)HCl(2)O(4)(-), (I), and diethylammonium chloranilate,
      C(4)H(12)N(+).C(6)HCl(2)O(4)(-), (II), the chloranilate ions are present as a
      hydrogen-bonded dimer which has an inversion center. The ethylammonium and
      diethylammonium ions link the dimers through N-H.O hydrogen bonds, forming a
      three-dimensional hydrogen-bond network in (I) and a one-dimensional chain in
      (II).

PMID- 15263152
TI  - Methyl 3-para-anisyl-4-(2-hydroxybenzoyl)isoxazole-5-carboxylate.
AB  - The title compound, C(19)H(15)NO(6), contains a planar isoxazole ring. An
      intramolecular hydrogen bond is formed between the OH group attached to a phenyl
      ring and a carbonyl O atom.

PMID- 15263153
TI  - N-(p-Chlorophenyl)-3,3-diphenyl-4-(beta-phenylstyryl)azetidin-2-one.
AB  - In the title compound, C(35)H(26)ClNO, the four-membered beta-lactam ring is
      essentially planar, with a maximum deviation of 0.012 (1) A for the N atom. The C
      C bond lengths in the beta-lactam ring are 1.591 (2) and 1.549 (2) A. The two
      phenyl rings attached to the beta-lactam ring are nearly perpendicular to each
      other [83.2 (1) degrees ].

PMID- 15263154
TI  - A novel heterocyclic sulfonamide: N-benzyl-5-[N-benzyl-N-(tert
      butyloxycarbonyl)amino]-N-(tert-butyloxycarbonyl)-1,3,4-thiadiazole-2
      sulfonamide.
AB  - The title compound, C(26)H(32)N(4)O(6)S(2), is a heterocyclic sulfonamide which
      is a 1,3,4-thiadiazole derivative. Structural data for this compound are compared
      with those of related compounds.

PMID- 15263155
TI  - A new amidrazone derivative with antimycobacterial activity.
AB  - Of a series of pyridine-2-carboxamidrazone derivatives with activity against
      mycobacteria, the N(1)-[4-(1,1-dimethylpropyl)benzylidene] derivative reported
      here, C(18)H(22)N(4), is one of the most active. The predicted E isomer about the
      C11=N12 double bond is confirmed and intramolecular hydrogen bonding involving
      both amino H atoms helps to keep the molecule flat. The same donor and acceptor
      atoms also form intermolecular hydrogen bonds.

PMID- 15263156
TI  - 1-Chloro-1,1-difluoro-N-(4-methoxyphenyl)-3-(pyrrolidin-2-ylidene)propan-2-imine.
AB  - In the title compound, C(14)H(15)ClF(2)N(2)O, the Z configuration has been
      confirmed. The molecular structure shows an intramolecular N-H.N hydrogen bond
      [H.N 2.04 (6), N.N 2.709 (6) A and N-H.N 124 (5) degrees ]. This interaction
      could be responsible for the Z configuration.

PMID- 15263157
TI  - (1R*,11R*)-Bicyclo[9.4.1]hexadecane-12,16-dione.
AB  - The title compound, C(16)H(26)O(2), (I), prepared by oxidation of (1R*,11R*)-12
      hydroxybicyclo[9.4.1]hexadecan-16-one using pyridinium dichromate, has a trans
      configuration of the two fused rings and represents an interesting precursor for
      the synthesis of macrocyclic structures.

PMID- 15263158
TI  - 2(S)-Amino-3-[1H-imidazol-4(5)-yl]propyl cyclohexylmethyl ether dihydrochloride
      and 2(S)-amino-3-[1H-imidazol-4(5)-yl]propyl 4-bromobenzyl ether dihydrochloride.
AB  - (Cyclohexylmethyloxymethyl)(1H-imidazol-4-iomethyl)-(S)-ammonium dichloride,
      C(13)H(25)N(3)O(+).2Cl(-), and (4-bromobenzyl)(1H-imidazol-4-iomethyl)-(S)
      ammonium dichloride, C(13)H(18)BrN(3)O(+).2Cl(-), are model compounds with
      different biological activities for evaluation of the histamine H3-receptor
      activation mechanism. Both title compounds occur in almost similar extended
      conformations.

PMID- 15263159
TI  - (1R*,2R*)-1,2-(2,3-Dimethoxybutane-2,3-dioxy)cyclohexane.
AB  - The title compound, 2,3-dimethoxy-2,3-dimethyl-5,6,7,8-tetrahydro-4-oxachroman,
      C(12)H(22)O(4), was synthesized as a model compound for substituted diequatorial
      fixed vicinal trans-cyclohexanediols.

PMID- 15263160
TI  - Bis(N,N-diethyl-1,1-diselenocarbamato-Se)selenium, [(Se(2)CNEt(2))(2)Se].
AB  - The polyseleno title compound, bis(N,N-diethylselenocarbamoyl) triselenide,
      [(Se(2)CNEt(2))(2)Se] or C(10)H(20)N(2)Se(5), is obtained from the disproportion
      of sodium N,N-diethyl-1,1-diselenocarbamate. An Se atom connects two N,N-diethyl
      1,1-diselenocarbamate groups with Se-Se distances in the range 2.4500 (11)-2.8601
      (12) A

PMID- 15263161
TI  - N-Benzyl-N-(4-methoxyphenyl)cyclohex-1-enecarbothioamide.
AB  - The crystal structure of the title thioamide, C(21)H(23)NOS, was determined to
      investigate the relationship between the photostability in the solid state and
      the structure.

PMID- 15263162
TI  - (1R,2R,3S,4S)-2-[(2R,3S)-2,3-Dimethyloxiran-2-yl]-3,4-bis(4
      methoxybenzyloxy)cyclohexanol.
AB  - The relative configuration was determined for the title compound, C(26)H(34)O(6),
      which was prepared in a synthetic study on immunosuppressant FR65814. There is an
      intramolecular hydrogen bond between the hydroxy and epoxy groups.

PMID- 15263163
TI  - (2S,3R,4S,5R,6S)-6-Benzyloxymethyl-4-(methoxymethyloxy)-9-oxo-8-oxa-1
      azabicyclo[4.3.0]nonane-2,3,5-triyl triacetate.
AB  - The relative configuration of the title compound, C(23)H(29)NO(11), prepared in a
      synthetic study on the natural product sphingofungin E, has been determined. The
      six-membered ring adopts a chair form and the five substituents are all axial.

PMID- 15263164
TI  - tert-Butyl 2-[2-(ethoxycarbothioylamino)-3-pyridyloxy]acetate and tert-butyl 2-(3
      thioxopyrido[2,1-c][1,2,4]thiadiazol-8-yloxy)acetate.
AB  - Compounds (I), C(14)H(20)N(2)O(4)S, and (II), C(12)H(14)N(2)O(3)S(2), are two
      minor products of the same reaction. Both structures contain identical ester
      functionalities in similar orientations. Both independent molecules of (I)
      contain an ethoxycarbothioylamine moiety, whilst (II) possesses a novel exocyclic
      thione system fused with a pyridine ring.

PMID- 15263165
TI  - 2-Acetyl-4H-benzothiazin-3(2H)-one.
AB  - The title compound, C(10)H(9)NO(2)S, has a boat-shaped heterocyclic six-membered
      ring such that the S and N atoms lie essentially in the plane of the benzene ring
      while the remaining two C atoms are above this plane.

PMID- 15263166
TI  - Absolute configuration of exo-syn-syn-dicarbonyl(eta(5)-cyclopentadienyl)[(1,2,3
      eta)-(1R,2S,3S)-1-phenylbut-2-en-1-yl]molybdenum(II). Erratum.
AB  - In the paper by Kuhl, Farrugia & Kocienski [Acta Cryst. (1999), C55, 2041-2043],
      the published scheme is incorrect. The correct scheme is given below.

PMID- 15263168
TI  - trans-(Methanol)(methyldiphenylphosphine)bis(pentane-2,4-dionato)cobalt(III)
      hexafluorophosphate hydrate.
AB  - The title compound [Co(C(5)H(7)O(2))(2)(C(13)H(13)P)(CH(4)O)]PF(6).H(2)O, (I),
      which was converted from trans-[Co(acac)(2)(PMePh(2))(H(2)O)]PF(6) (acac is
      pentane-2,4-dionato) by recrystallization from aqueous methanol, has been
      confirmed as have a coordinated methanol ligand. The molecular structure of the
      complex cation, trans-[Co(acac)(2)(PMePh(2))(MeOH)](+), is similar to that of the
      above aqua complex found in the ClO(4) salt [Kashiwabara et al. (1995). Bull.
      Chem. Soc. Jpn, 68, 883-888]. The Co-O bond length for the coordinated methanol
      is 2.059 (3) A. There is an intermolecular hydrogen bond between the OH group of
      the coordinated methanol and one of the O atoms of the acac ligands in an
      adjacent complex cation [O5.O3' = 2.914 (4) A], giving a centrosymmetric dimeric
      dicationic complex.

PMID- 15263167
TI  - K(9)CeP(4)S(16), a new thiophosphate of cerium with discrete [Ce(PS(4))(4)](9-)
      anions.
AB  - The structure of nonapotassium cerium tetraphosphorus hexadecasulfide, a zero
      dimensional material isostructural with Rb(9)CeP(4)Se(16), is reported.

PMID- 15263169
TI  - Di-micro-acetato-O:O'-di-micro-acetato-O,O':O'
      bis{[(cyclopentadienyl)tris(dimethylphosphito-P)cobalt-O,O',O"]neodymium(III)}
AB  - In the title compound, [{eta(5)-CpCo[P(O)(OMe)(2)](3)}Nd(O(2)CCH(3))(2)](2), with
      a centrosymmetric molecule, each Nd atom has an eight-coordination environment,
      surrounded by a tripodal {L(OMe) = CpCo[P(O)(OMe)(2)](3)} and four bridging
      acetato ligands. The coordination geometry around each Nd centre is described as
      a distorted square-antiprism and the two different types of acetato ligands have
      micro-O:O'- and micro-O,O':O'-acetato coordination modes. The Nd-O distances are
      in the range 2.378 (4)-2.594 (5) A and the Nd.Nd distance is 3.9913 (6) A.

PMID- 15263170
TI  - [N,N'-Bis(salicylidene)-1,2-diphenyl-(RS,SR)-1,2-ethanediaminato]nickel(II).
AB  - In crystals of the title compound, [Ni(C(28)H(22)N(2)O(2))], the coordination
      geometry around the Ni atom is square planar with a slight tetrahedral
      distortion. The five-membered N,N'-chelate ring adopts a distorted gauche
      conformation with the two phenyl groups in axial and equatorial orientations.

PMID- 15263171
TI  - cis-Diaquabis(trans-cinnamato-O,O')zinc(II).
AB  - The title complex, [Zn(C(9)H(7)O(2))(2)(H(2)O)(2)], shows a distorted octahedral
      coordination and has a crystallographic twofold rotation axis. Intermolecular O
      H.O hydrogen bonding forms a two-dimensional network in the ab plane.

PMID- 15263172
TI  - Bis(tetraethylammonium) tetraiodozincate at 150 and 301 K.
AB  - The refinements described here for (NEt(4))[ZnI(4)] completely confirm the
      results previously obtained for the isostructural tetrabromocadmate at room
      temperature [Geselle & Fuess (1994). Acta Cryst. C50, 1582-1585]. Here again,
      isolated MX(4) (M = Zn and X = I) tetrahedra are accompanied by two cations in a
      'swastika' conformation and a third in a virtually planar trans conformation. One
      of the former cations is particularly disordered.

PMID- 15263173
TI  - Monoclinic and triclinic forms of bis[2-hydroxy-2,2-bis(2-pyridyl)ethanoato
      O(1),N,N']nickel(II).
AB  - Reaction of pyridoin with nickel nitrate in methanol in air gives crystals of two
      forms of the title compound, [Ni(C(12)H(9)N(2)O(3))(2)]; a triclinic form with
      the Ni atom on an inversion centre and a monoclinic form with one molecule in a
      general position in the asymmetric unit. Both forms show an octahedral nickel
      centre coordinated by two facial tridentate ligands with their O-atom donors
      trans.

PMID- 15263174
TI  - (micro-C-meso-5,5,7,12,12,14-Hexamethyl-1,4,8,11-tetraazacyclotetradecane-N
      acetato-1kappa(5)N,N',N",N"',O:2kappaO')tetrachloro-1kappaCl,2kappa(3)Cl
      cobalt(III)zinc(II).
AB  - The crystal structure of the title compound, [CoCl(C(18)H(37)N(4)O(2)){ZnCl(3)}],
      has been determined by X-ray diffraction.C-meso-5,5,7,12,12,14-Hexamethyl
      1,4,8,11-tetraazacyclotetradecane-N-acetate acts as a bridging ligand to
      coodinate with Co(III) and Zn(II) ions. The Co(III) ion is six-coordinate in a
      nearly octahedral environment provided by one Cl atom, four N atoms of the
      bridging ligand, and one O atom. The Zn(II) ion is four-coordinate in a distorted
      tetrahedral environment completed by three Cl atoms and an O atom of the bridging
      ligand.

PMID- 15263175
TI  - Tris(8-quinolinolato-N,O)cobalt(III) ethanol solvate.
AB  - In the crystal of the title complex, [Co(C(9)H(6)NO)(3)].C(2)H(5)OH, the central
      Co atom has a distorted octahedral coordination comprised of three N atoms and
      three O atoms from the three 8-quinolinolato ligands. The three Co-O bond
      distances are in the range 1.887 (2)-1.910 (2) A, while the three Co-N bond
      distances range from 1.919 (2) to 1.934 (2) A. The solvent ethanol molecule forms
      an intermolecular O-H.O hydrogen bonding with a quinolinolato ligand.

PMID- 15263176
TI  - cis-Dichloro(dimethylaminomethylene)(triphenylphosphine)palladium(II) acetone
      solvate.
AB  - The synthesis and X-ray structural analysis of the title compound,
      [PdCl(2)(C(3)H(7)N)(C(18)H(15)P)].C(3)H(6)O, are described. The crystal structure
      contains discrete monomeric molecules of the carbene complex and solvent
      molecules separated by normal van der Waals distances. The Pd atom is four
      coordinate in an essentially square-planar environment, with the chlorine ligands
      mutually cis; Pd-P = 2.2495 (7), Pd-Cl = 2.3508 (7) and 2.3600 (7), Pd-C 1.948
      (2) and N-C(carbene) 1.274 (3) A.

PMID- 15263177
TI  - Bis(isopropylamino)methylcarbenium tetrakis(pentafluorophenyl)gallate.
AB  - The title compound, [MeC(NH(i)Pr)(2)][Ga(C(6)F(5))(4)] crystallizes as discrete
      ions forming interionic hydrogen bonds of the type N-H.F.

PMID- 15263178
TI  - A chiral furocoumarin.
AB  - The furocoumarin 1,2-dihydro-2-(1,2-dihydroxyprop-2-yl)-8H-furo[2,3-h]benzopyran
      8-one crystallizes from methanol-water as the monohydrate C(14)H(14)O(5).H(2)O.
      Both chiral centers have the S configuration. Both OH groups and both H atoms of
      the water molecule form intermolecular hydrogen bonds with O.O distances in the
      range 2.7686 (18)-2.8717 (18) A.

PMID- 15263179
TI  - (2R,3R,4R,5S)-3,4,5-Trihydroxy-2-(2-hydroxyethyl)piperidinium chloride.
AB  - The absolute configuration at the new stereogenic centre during the key step of
      the total synthesis was established byX-ray analysis of the title compound,
      C(7)H(15)NO(4)(+).Cl(-).

PMID- 15263180
TI  - Triethylammonium hydrogen fumarate.
AB  - In crystals of the title compound, the hydrogen fumarate anions form one
      dimensional chains through an O-H.O hydrogen bonding along the c and (a+b)/2
      directions. There are three sites of the hydrogen fumarate, two of which have an
      inversion centre.

PMID- 15263181
TI  - (-)-(3S)-4-(2-{[4,4-Dimethoxy-6-(benzyloxymethyl)perhydropyran-2-yl]methyl}-1,3
      dithian-2-yl)-4-methyl-3-(1,1,2,2-tetramethyl-1-silapropoxy)pentan-1-ol.
AB  - The absolute configuration was determined for the title compound, (-)
      C(32)H(56)O(6)S(2)Si, (I), which was prepared in a synthetic study on the natural
      products bryostatins. Two independent molecules show similar conformations,
      except for the orientation of the methoxy groups.

PMID- 15263182
TI  - (+)-3-{(4S,5S)-5-[1,1-Dimethyl-2-(phenylthio)ethyl]-2,2-dimethyl-1,3-dioxolan-4
      yl}prop-2-yn-1-ol.
AB  - The absolute configuration was determined for the title compound, (+)
      C(18)H(24)O(3)S, (I), which was prepared in a synthetic study on the natural
      products, bryostatins.

PMID- 15263183
TI  - Charge-transfer complexes of N-methyl-, N-isopropyl-, N-butyl- and N
      isobutylcarbazole with 3,5-dinitrobenzoic acid.
AB  - In the title four compounds, C(13)H(11)N.C(7)H(4)N(2)O(6), (I),
      C(15)H(15)N.C(7)H(4)N(2)O(6), (II), C(16)H(17)N.C(7)H(4)N(2)O(6), (III), and
      C(16)H(17)N.C(7)H(4)N(2)O(6), (IV), the donor and acceptor molecules are stacked
      alternately to form one-dimensional columns. In (I), the N-methyl group of the
      donor is nearly eclipsed with respect to one of the nitro groups of the
      neighboring acceptor in a column, whereas the N-isopropyl, N-butyl and N-isobutyl
      groups are in anti positions with respect to one of the nitro groups of the
      neighboring acceptor in compounds (II)-(IV).

PMID- 15263184
TI  - Charge-transfer complexes of N-methyl-and N-ethylcarbazole with 3,5
      dinitrobenzonitrile.
AB  - In the two title compounds, N-methylcarbazole-3,5-dinitrobenzonitrile (1/1),
      C(13)H(11)N.C(7)H(3)N(3)O(4), (I), and N-ethylcarbazole-3,5-dinitrobenzonitrile
      (1/1), C(14)H(13)N.C(7)H(3)N(3)O(4), (II), the donor and acceptor molecules are
      stacked alternately to form one-dimensional columns. In (I), the N-methyl group
      of the donor is nearly eclipsed with respect to one of the nitro groups of the
      neighboring acceptor in a column, whereas the N-ethyl group is anti with respect
      to the cyano group of the neighboring acceptor in (II).

PMID- 15263185
TI  - Charge-transfer complexes of 4-(dimethylamino)pyridine with 2,4-, 3,4- and 3,5
      dinitrobenzoic acid.
AB  - In the three title crystal structures 4-(dimethylamino)pyridinium 2,4
      dinitrobenzoate, (I), 4-(dimethylamino)pyridinium 3,4-dinitrobenzoate, (II), and
      4-(dimethylamino)pyridinium 3,5-dinitrobenzoate, (III), all
      C(7)H(11)N(2)(+).C(7)H(3)N(2)O(6)(-), the ions are connected by an N-H.O hydrogen
      bond. Dihedral angles between the pyridine and phenyl rings are 69.9 (1), 26.7
      (1) and 56.2 (1) degrees in (I), (II) and (III), respectively. Donor-acceptor pi
      pi stacking is observed in (II) and (III), but not in (I).

PMID- 15263186
TI  - N-Benzyl-N-(2-methoxyphenyl)cyclohex-1-enecarboxamide.
AB  - The title amide, C(21)H(23)NO(2), (I), does not photocyclize in the solid state.
      The methoxy group is involved in intermolecular steric interactions and so
      prevents the rotation of the N-phenyl group in the crystal.

PMID- 15263187
TI  - N-Isopropyl-N-[(E)-2-phenylpropenyl]thiobenzamide and N-isopropyl-3-methoxy-N
      [(E)-2-phenylpropenyl]thiobenzamide.
AB  - The crystal structures of the two title thiobenzamides, C(19)H(21)NS, (I), and
      C(20)H(23)NOS, (II), were determined to investigate the relationship between the
      photoreactivity in solid state and the structure. Their geometry was confirmed to
      be the E isomer in each case.

PMID- 15263188
TI  - N-Methyl-N-[(Z)-2-phenylpropenyl]thiobenzamide.
AB  - The crystal structure of the title thiobenzamide, C(17)H(17)NS, was determined to
      investigate the relationship between the photoreactivity in solid state and the
      structure. The geometry was confirmed to be the Z isomer.

PMID- 15263189
TI  - 2-Isopropyl-4-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-1-thione.
AB  - The title compound, C(19)H(21)NS, is the photoproduct obtained from N-isopropyl-N
      [(E)-2-phenylpropenyl]thiobenzamide. Recrystallization showed a spontaneous
      resolution.

PMID- 15263190
TI  - A double mesogen based on linked p-terphenyl units.
AB  - The structure of bis(4,4"-decyloxy-p-terphenyl-2'-ylmethyl) carbonate,
      C(79)H(110)O(7), (I), has been determined at 123 K. It is a new type of twin
      mesogen. No two adjacent aromatic rings are coplanar and the four decyloxy side
      chains are maximally extended. Molecules of the compound are packed along the
      crystallographic a axis. The molecular arrangement is a precursor of a smectic A
      phase.

PMID- 15263191
TI  - Intermolecular hydrogen bonding of the two independent molecules of N-3,5
      dinitrobenzoyl-L-leucine.
AB  - The title compound, C(13)H(15)N(3)O(7), crystallizes as two independent molecules
      which differ in their conformation. Intermolecular hydrogen bonding between the
      amide and carboxylic acid groups as N-H.O=C interactions results in the formation
      of one-dimensional chains with N.O distances of 2.967 (6) and 3.019 (6) A.
      Neighbouring chains are linked by C=O.H-O interactions to form a two-dimensional
      network, with O.O distances of 2.675 (6) and 2.778 (6) A.

PMID- 15263192
TI  - A second polymorphic form of N,N'-diphenyl-1,4-phenylenediamine.
AB  - A new triclinic polymorphic form of N,N'-diphenyl-1,4-phenylenediamine
      (C(6)H(5)NHC(6)H(4)NHC(6)H(5)) has been obtained through appropriate
      recrystallization of the orthorhombic form. It crystallized in the
      centrosymmetric space group P$?overline 1$, with two half molecules as the
      asymmetric unit.

PMID- 15263193
TI  - 2,2'-Spirobi(1,3-benzodithiole).
AB  - The X-ray structure analysis of 2,2'-spirobi(1,3-benzodithiole), C(13)H(8)S(4),
      has been performed. The molecule has crystallographic twofold rotation symmetry,
      the axis passing through the spiro-C atom. The four S atoms are arranged around
      the spiro-C atom in two almost orthogonal CS(2) planes. However, because of large
      bending of the two five-membered rings, close contact is present between two
      connected C atoms on the benzo group of each 1,3-benzodithiole ring and one S
      atom on the other 1,3-benzodithiole ring.

PMID- 15263194
TI  - 4-Phenylbutan-2-one semicarbazone.
AB  - The title compound, C(11)H(15)N(3)O, crystallizes with two molecules in the
      asymmetric unit, which are held together by an extended network of hydrogen
      bonds. It is remarkable that only five of the six theoretically possible hydrogen
      bonds are formed.

PMID- 15263195
TI  - 1,2,4-Triazolo[2,3-h]-7,9-thiaza-11-crown-4.
AB  - The title compound, 4,7-dioxa-10-thia-1,12,13-triazabicyclo[9.3.0]tetradeca-11,13
      diene, C(8)H(13)N(3)O(2)S, contains an 11-membered ring, which appears in a chair
      conformation and has approximate mirror symmetry. It may be used for the
      complexation of metal atoms.

PMID- 15263196
TI  - 4-Acetonylidene-1-ethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one.
AB  - The title compound, C(14)H(16)N(2)O(2), contains a diazepine ring, which appears
      in a boat conformation. An intramolecular hydrogen bond is formed between the NH
      group of the diazepine ring and a carbonyl O atom of one of the side chains.

PMID- 15263197
TI  - 1,3,5-Tris(chloromethyl)benzene.
AB  - The title compound, C(9)H(9)Cl(3), is being used as a platform for new tripodal
      receptors. Two molecules make up the asymmetric unit; weak intermolecular
      hydrogen bonding is observed between methylene H atoms and the chlorine of an
      adjacent molecule. There are also C-H.pi interactions.

PMID- 15263198
TI  - 4-Hydroxy-1-methyl-2-oxo-N-(4-oxo-2-propyl-3,4-dihydroquinazolin-3-yl)-1,2
      dihydroquinoline-3-carboxamide.
AB  - The two bicyclic fragments of the title compound, C(22)H(20)N(4)O(4), are
      individually planar and are turned with respect to each other by 77.8 (2)
      degrees. The formation of intramolecular O-H.O and N-H.O hydrogen bonds causes
      considerable changes in the bond lengths within the amidopyridine fragment.

PMID- 15263199
TI  - A single-crystal neutron diffraction study of RbTiOAsO(4).
AB  - A rubidium titanyl arsenate single-crystal has been studied by neutron
      diffraction (lambda = 1.207 A). The polished sample used was 5 x 3 x 2 mm and was
      cut from a crystal made by top-seeded solution growth. The crystal showed severe
      extinction. It was, however, possible to obtain a structural model with well
      defined oxygen sites and reasonable anisotropic displacement parameters.

PMID- 15263200
TI  - Tetrapotassium disodium decavanadate(V) decahydrate.
AB  - The title compound, K(4)Na(2)[V(10)O(28)].10H(2)O, is isostructural with the
      known disodium tetraammonium salt of the centrosymmetric [V(10)O(18)](6-) anion.

PMID- 15263201
TI  - Redetermination of [Ni(NH(3))(6)]Cl(2) at 173 K.
AB  - The structure of hexaamminenickel(II) dichloride determined previously by Essmann
      et al. [Essmann, Kreiner, Niemann, Rechenbach, Schmieding, Sichla, Zachwieja &
      Jacobs (1996). Z. Anorg. Allg. Chem. 622, 1161-1166] was redetermined at 173 K.
      There are no significant differences between these two structures.

PMID- 15263202
TI  - [{Me(4)C(2)(C(5)H(4))(2)}Zr(BH(4))(2)], a bis(tetrahydroborate) complex of a
      bridged zirconocene.
AB  - Bis(tetrahydroborato)[1,1,2,2-tetramethyl-1,2-ethylenebis(eta(5)
      cyclopentadienyl)]zirconium, (I), was synthesized by the reaction of the
      zirconocene dichloride with lithium tetrahydroborate. Crystals suitable for X-ray
      structure analysis were obtained by recrystallization from toluene. The molecule
      adopts an appproximate C(2v) symmetry. Both tetrahydroborate ligands are eta(2)
      coordinated and tilted by 18-19 degrees out of the equatorial plane; the angle B1
      Zr1-B2 is 104.7 degrees. The cyclopentadienyl rings show a normal eta(5)
      coordinaton, with a centroid-Zr-centroid angle of 124.3 degrees.

PMID- 15263203
TI  - trans-Diaquabis(N-acetylanthranilato-O,O')copper(II).
AB  - The title monomeric copper(II) complex, [Cu(C(9)H(8)NO(3))(2)(H(2)O)(2)], (I),
      shows a square-planar coordination and has an inversion centre at the Cu atom.
      The carboxylate group of the N-acetylanthranilate ion acts as a monodentate donor
      ligand to copper and as an acceptor of an intramolecular O-H.O hydrogen bond from
      the coordinated water molecule, with an O.O distance of 2.581 (2) A.

PMID- 15263205
TI  - Hexakis(antipyrine-O)terbium(III) triperchlorate.
AB  - In the title compound, hexakis(1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one
      O)terbium(III) triperchlorate, [Tb(C(11)H(12)N(2)O)(6)](ClO(4))(3), the Tb atom
      lies on a site of $?overline 3$ crystallographic symmetry and the unique Tb-O
      distance is 2.278 (2) A. One of the perchlorate anions has threefold
      crystallographic symmetry, while the other is disordered about a $?overline 3$
      site.

PMID- 15263204
TI  - catena-Poly[[tetrakis(micro-2,2-dimethylpropionato-O:O')dicopper(II)]-micro
      dioxane-O:O'] and catena-poly[[tetrakis(micro-3,3-dimethylbutyrato
      O:O')dicopper(II)]-micro-dioxane-O,O'].
AB  - The title two compounds, [Cu(2)(C(5)H(9)O(2))(4)(C(4)H(8)O(2))](n), (I), and
      [Cu(2)(C(6)H(11)O(2))(4)(C(4)H(8)O(2))](n), (II), are isomorphous. The binuclear
      Cu(II) units have a cage structure and are linked by the dioxane molecules to
      form a zigzag chain along the c axis. The binuclear copper unit and the dioxane
      ligand each have a centre of symmetry.

PMID- 15263206
TI  - Bis[N,N-bis(2-hydroxyethyl)dithiocarbamato]dimethyltin(IV).
AB  - The title compound, [Sn(CH(3))(2)(C(5)H(10)NO(2)S(2))(2)], has crystallographic
      mirror symmetry (C-Sn-C on mirror plane) and the coordination polyhedron around
      the Sn atom is a tetrahedron [C-Sn-C 139.3 (2) degrees and S-Sn-S 82.3 (1)
      degrees ] distorted towards a skew-trapezoidal bipyramid owing to an
      intramolecular Sn.S contact [3.0427 (6) A]. The molecules are linked into a
      linear chain by intermolecular O-H.O hydrogen bonds [O.O 2.646 (3) A].

PMID- 15263207
TI  - Orthorhombic modification of triphenyltin 3-ureidopropionate.
AB  - The Sn atom in catena-poly[triphenyltin(IV)-micro-(3-ureidopropionato
      O(1):O(3))], [Sn(C(6)H(5))(3)(C(4)H(7)N(2)O(3))](n), is five-coordinate and has a
      trans-C(3)SnO(2) trigonal-bipyrmidal geometry arising from bridging through the O
      atom of the ureido fragment of an adjacent carboxylate group. Infinite chains
      propagate helically along the c axis and adjacent chains are linked by N-H.O [N.O
      2.851 (4) A] hydrogen bonds into layers.

PMID- 15263208
TI  - A highly functionalized ferrocenylpyrazolo[2,3-a]pyridine.
AB  - The crystal structure of [2-(4-bromophenyl)-4-cyano-5-ferrocenylpyrazolo[2,3
      a]pyridin-7-yl]acetonitrile, C(26)H(17)N(4)FeBr or
      [Fe(C(5)H(5))(C(21)H(12)BrN(4))], shows that the pyrazolopyridine ring system
      (PP), the bromophenyl ring (BP) and the cyclopentadiene ring (Cp) are nearly
      planar. The PP ring system is twisted out of the plane of the BP and Cp rings by
      about 20 degrees.

PMID- 15263209
TI  - 2,3,4,5-Tetrakis[(2-hydroxyethyl)thio]tetrathiafulvalene tetrafluoroborate.
AB  - The title complex, C(14)H(20)O(4)S(8)(+)(.)BF(4)(-), is a charge-transfer complex
      with typical charges for the donor and anion of +1 and -1, respectively. Two
      centrosymmetrically related donors form a face-to-face pi-dimer with a strong
      intermolecular S.S interaction. These pi-dimers stack along the a axis to form a
      donor column. The structure is extensively hydrogen bonded.

PMID- 15263210
TI  - 2,2'-Bi(9,9-dihexylfluorene).
AB  - The central part of the title molecule, C(50)H(66), is planar, all the rings
      being in the same plane; the lateral chains are also planar (excluding H atoms),
      almost perpendicular to the ring plane and grafted on the same side of the
      molecule. The molecule has nearly a mirror plane, perpendicular to the central C
      C bond, instead of the centre of symmetry expected. The orientation of the plane
      of the rings is approximately 45 degrees from the unit-cell b axis, so that
      neighbouring molecules are essentially perpendicular.

PMID- 15263211
TI  - Pyridinium dihydrogenmonothiophosphate.
AB  - By reaction of pyridine dithiomonometaphosphoryl fluoride with
      ethyldiphenylphosphine in the presence of traces of water, we isolated crystals
      of the title compound, (I). In the structure of this salt, two kinds of hydrogen
      bonds were detected. They link N-H (part of the cation), as well as one O-H group
      (part of the anion), to the phosphoryl O atom of the anion. The donor-acceptor
      distances are 2.654 (1) and 2.568 (1) A, respectively. The P-O and P-S bond
      lengths are 1.514 (2) and 1.967 (1) A, respectively, which fall therefore in the
      range of a 1.5-fold bond.

PMID- 15263212
TI  - A monoclinic polymorph of bis(tert-butylperthiophosphonic) dianhydride.
AB  - In comparison with the known orthorhombic polymorph oftrans-2,4-di-tert-butyl-2,4
      dithioxo-1,3-dithia-2,4-diphosphetane, C(8)H(18)P(2)S(4), (I) [Shore, Pennington,
      Noble & Cordes (1988). Phosphorous Sulfur, 39, 153-157], the new crystallographic
      modification is monoclinic and the corresponding solid density is markedly
      higher. In both structures, the molecules have 2/m symmetry imposed by space
      group symmetry and all corresponding bond lengths and angles are equal within the
      limits of errors.

PMID- 15263213
TI  - Caulerpin.
AB  - The crystal structure of caulerpin (dimethyl 6,13-dihydrodibenzo[b,i]phenazine
      5,12-dicarboxylate, C(24)H(18)N(2)O(4)), an indole alkaloid, reported in space
      group Cc with an acute beta angle, has been redetermined in the correct space
      group, C2/c. The molecule has twofold crystallographic symmetry and is composed
      of two essentially planar indole groups fused to an eight-membered
      cyclooctatetraene ring which adopts a boat conformation. The molecular dimensions
      are normal. The structure is stabilized by intermolecular and intramolecular
      interactions involving the indole N-H atom and carbonyl O atom [N.O 3.211 (4) and
      2.836 (4) A].

PMID- 15263214
TI  - Tribenzylphosphine oxide.
AB  - The title compound, (C(6)H(5)CH(2))(3)PO, is an organic tertiary phosphine oxide.
      The molecule has threefold symmetry, with the P-O bond along the threefold axis.
      Main dimensions include P-O 1.488 (4), P-C 1.823 (3) A and O-P-C 114.7 (1)
      degrees. The crystals were accidentally obtained when preparing complexes of
      nickel(II) with dibenzylphosphine.

PMID- 15263215
TI  - N-Acetyl-L-phenylalanine.
AB  - The structure of the title compound, C(11)H(13)NO(3), is characterized by a two
      dimensional infinite network of intermolecular N-H.O and O-H.O hydrogen bonds.

PMID- 15263217
TI  - The low-temperature study of D- and DL-camphoric anhydride.
AB  - The low-temperature crystal stuctures of D- and DL-camphoric anhydride,
      C(10)H(14)O(3), have been determined by X-ray diffraction methods. Although the
      two enantiomers crystallize in different space groups, the cell volumes and
      densities are essentially the same. The six-membered rings deviate significantly
      from planarity, both exhibiting half-boat conformations. The dihedral angle
      between the six- and five-membered rings is 80.3 (1) degrees in both cases. The
      main difference in the molecular stuctures can be described by two torsion angles
      associated with the H atoms of the methyl substituents. The packing of the
      racemic and chiral structures are essentially the same.

PMID- 15263216
TI  - Bis[2-(diphenylphosphinoyl)benzene] disulfide.
AB  - The title compound, [2-Ph(2)P(O)C(6)H(4)S](2) or C(36)H(28)O(2)P(2)S(2), obtained
      by electrochemical oxidation of 2-(diphenylphosphino)benzenethiol, has twofold
      crystallographic symmetry. Principal dimensions include S-S 2.0212 (15) A, S-C
      1.786 (3) A and C-S-S-C 81.34 (14) degrees.

PMID- 15263218
TI  - A T-shaped selenenyl halide.
AB  - The title selenenyl halide complex, 3-iodo-2-phenyl-3H-3-selenaindazole,
      C(12)H(9)IN(2)Se, has an almost planar conformation and a nearly ideal T-shape
      for the Se(INC) moiety [Se-I 2.8122 (12), Se-C 1.881 (7) and Se-N2 2.051 (6) A; C
      Se-N 79.6 (3), C-Se-I 96.8 (2) and N-Se-I 176.17 (17) degrees ]. This
      arrangement, together with the two selenium lone pairs, leads to a distorted
      trigonal-bipyrimidal geometry about the Se atom. Intermolecular interactions are
      largely limited to stacking forces.

PMID- 15263219
TI  - trans-1-Cyano-2-(2-methoxyphenyl)-1-nitroethylene.
AB  - The title compound, C(10)H(8)N(2)O(3), has been prepared by condensation of 2
      methoxybenzaldehyde and nitroacetonitrile in ethanol at room temperature. Its
      investigation has been undertaken as a part of search for new nonlinear optical
      compounds. The pi-conjugated molecule is almost planar. Molecules in the crystal
      are packed in stacks with antiparallel molecular orientation and slightly
      alternating distances between mean molecular planes.

PMID- 15263220
TI  - 7,7-Dichloro-1,6-dimethyl-2-oxa-5-thiabicyclo[4.1.0]heptane 5,5-dioxide and 6
      chloro-2,3-dihydro-7-methyl-5-methylene-2H,3H,5H-1,4-dithiepine 1,1,4,4
      tetraoxide.
AB  - The structures of a 2-oxa-5-thiabicyclo[4.1.0]heptane derivative,
      C(7)H(10)Cl(2)O(3)S, (I), and a 2H,3H,5H-1,4-dithiepine derivative,
      C(7)H(9)ClO(4)S(2), (II), are reported. The six-membered ring in (I) has an
      envelope conformation and the seven-membered ring in (II) adopts a chair
      conformation. There are no untoward intermolecular interactions in (I), but two
      Cl atoms make a short intermolecular contact across an inversion centre in (II),
      with a Cl.Cl distance of 3.2784 (9) A, some 0.22 A less than the sum of the van
      der Waals radii.

PMID- 15263221
TI  - Bis(dicyclohexylammonium) adipate monohydrate.
AB  - In the asymmetric unit of the title compound, 2C(12)H(24)N(+).C(6)H(8)O(4)(2
      ).H(2)O, the carboxylate ion lies about an inversion center, the water molecule
      is on a twofold axis and the sec-ammonium cation is in a general position.
      Cations link the oxygen ends of two adjacent carboxylate anions to form an eight
      membered ring [N.O 2.683 (3) and 2.711 (3) A]. The ion pair propagates as a
      linear chain and adjacent chains are linked through the water molecules [O.O
      2.966 (3) A] into layers.

PMID- 15263222
TI  - Bis(N,N-dimethylthiocarbamoylthio)acetic acid.
AB  - Bis(N,N-dimethylthiocarbamoylthio)acetic acid, [(CH(3))(2)NC(=S)S](2)CHC(=O)OH or
      C(8)H(14)N(2)O(2)S(4), exists as a centrosymmetric hydrogen-bonded dimer [O.O
      2.661 (3) A].

PMID- 15263223
TI  - Sparfloxacin, an antibacterial drug.
AB  - The title compound, sparfloxacin or cis-5-amino-1-cyclopropyl-7-(3,5
      dimethylpiperazin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
      trihydrate, C(19)H(22)F(2)N(4)O(3).3H(2)O, is an antibacterial drug. The
      molecule, which crystallizes as a trihydrate, is in the zwitterionic form in the
      solid state. Hydrogen bonds stabilize the molecules in the lattice.

PMID- 15263224
TI  - XAFS conference proceedings and JSR.

PMID- 15263225
TI  - The EXAFS family tree: a personal history of the development of extended X-ray
      absorption fine structure.
AB  - This paper reviews the history of X-ray absorption spectroscopy (XAS) beginning
      with the first observation of an absorption edge, through the development of the
      modern theory and data inversion by the Fourier transform. I stop with my first
      trip to a synchrotron X-ray source. The study of XAS began at an exciting time
      for science. Wave mechanics, X-ray diffraction, X-ray scattering from non
      crystalline materials experiments developed in parallel with XAS. However, the
      difficulty of obtaining data from conventional X-ray tubes limited the field to a
      potentially interesting minor subject. Only with the advent of synchrotron
      radiation and arrival of modern theory in the 1970s did XAS become widely
      applicable to fields ranging from environmental to biological sciences. Early
      developments in experimental technique and theory are emphasized. Since I worked
      in both the before-synchrotron and after-synchrotron time frames, I had the
      opportunity to meet some of the early scientists. A number of historical
      vignettes and photographs of the scientists involved in the development of EXAFS
      are presented.

PMID- 15263226
TI  - XAFS spectroscopy in catalysis research: AXAFS and shape resonances.
AB  - Two new techniques in X-ray absorption spectroscopy (XAS) have recently been
      developed which provide previously unobtainable information on supported noble
      metal catalysts. Atomic X-ray absorption fine structure (AXAFS) provides direct
      information on the average changes in interatomic potential of the metal
      particles induced by metal-support effects. Changes in the interatomic potential
      can now be directly related to changes in catalytic reactivity. Analysis of shape
      resonances near the X-ray absorption edge provides information on the changes in
      the nature of the bonding of adsorbates (like hydrogen) to the metal cluster as
      induced by the properties of the support. The strong decrease in activity of
      supported platinum clusters for neo-pentane hydrogenolysis with increasing
      alkalinity of the support can be ascribed to a decrease in ionization potential
      of the metal particles directly influenced by the alkalinity of the support.

PMID- 15263227
TI  - The XAFS beamline BL01B1 at SPring-8.

PMID- 15263228
TI  - Dispersive XAS at third-generation sources: strengths and limitations.

PMID- 15263229
TI  - XAFS spectra in the high-energy region measured at SPring-8.

PMID- 15263230
TI  - Sequence estimation of piled-up pulses in synchrotron-based XAFS.

PMID- 15263231
TI  - Rapid and sensitive XAFS using a tunable X-ray undulator.

PMID- 15263232
TI  - Laboratory diffractometer-based XAFS spectrometer.

PMID- 15263233
TI  - Conversion of the oldest XAFS station at the first dedicated SR source to a state
      of-the-art XAFS facility.

PMID- 15263235
TI  - Improved performance of an undulator soft X-ray station BL-2A of the Photon
      Factory in its reduced emittance operation.

PMID- 15263234
TI  - The ESRF beamline ID26: X-ray absorption on ultra dilute sample.

PMID- 15263236
TI  - A new approach for in-laboratory XAFS equipment.

PMID- 15263237
TI  - Design and possibilities of the materials science beamline at DELTA.

PMID- 15263238
TI  - Undulator QEXAFS at the ESRF beamline ID26.

PMID- 15263239
TI  - Performance of the ESRF ID26 beamline reflective optics.

PMID- 15263240
TI  - High-energy X-ray absorption spectroscopy at ESRF BM29.

PMID- 15263241
TI  - Design of an XAFS beamline at the Photon Factory: possibilities of bent conical
      mirrors.

PMID- 15263242
TI  - Enhancement of the Refl-EXAFS sensitivity using the whispering gallery effect.

PMID- 15263243
TI  - Cobalt silicide formation on 6H silicon carbide.

PMID- 15263244
TI  - Polarization-modulation technique with diamond phase retarder to improve the
      accuracy of XMCD measurements.

PMID- 15263245
TI  - Collecting XAFS spectra at soft X-ray energies in a heated loop cell up to 1600
      K.

PMID- 15263246
TI  - XAFS measurements on zinc chloride aqueous solutions from ambient to
      supercritical conditions using the diamond anvil cell.

PMID- 15263247
TI  - In situ EXAFS study of nickel hydroxide electrodes during discharge.

PMID- 15263248
TI  - Design and construction on an in situ cell for catalytic studies on elements with
      12 < Z < 20.

PMID- 15263249
TI  - The development of a combined simultaneous XAFS/FTIR facility for the study of
      matrix species.

PMID- 15263250
TI  - In situ XAFS studies of the adsorption of benzene in zeolite beta: differences
      between fluorescence and electron yield detection.

PMID- 15263251
TI  - A new approach for QEXAFS data acquisition.

PMID- 15263252
TI  - A bent Laue analyzer for fluorescence EXAFS detection.

PMID- 15263253
TI  - Edge-jump inversion in the Si L3,2-edge optical XAFS of porous silicon.

PMID- 15263254
TI  - The physics of ionization chambers - or how to improve your signal-to-noise ratio
      for transmission EXAFS measurements.

PMID- 15263255
TI  - Design and testing of a prototype multilayer analyzer X-ray fluorescence
      detector.

PMID- 15263256
TI  - Eu K-XAFS of europium dioxymono-cyanamide with the conversion He+ ion yield
      method.

PMID- 15263257
TI  - Estimation of the experimental standard deviations in EXAFS measurements.

PMID- 15263258
TI  - Amplitude reduction in EXAFS.

PMID- 15263259
TI  - Polymeric spin transition compounds: EXAFS and thermal behaviour.

PMID- 15263260
TI  - F-test in EXAFS fitting of structural models.

PMID- 15263261
TI  - Real-space multiple-scattering approach to XANES.

PMID- 15263262
TI  - The importance of multiple scattering pathways through the central atom in the
      analysis of metal K-edge XAFS data of coordination complexes.

PMID- 15263263
TI  - EXAFS of a tetragonally compressed Cu(II) compound.

PMID- 15263264
TI  - Numerical determination of a true absorption spectrum from grazing-incidence
      fluorescence EXAFS data.

PMID- 15263265
TI  - Iron surrounding in CaO-FeO-2SiO2 glass: EXAFS and molecular dynamics simulation.

PMID- 15263266
TI  - Linear inverse problem solution of the basic XAFS equation via the Wavelet
      Galerkin method.

PMID- 15263268
TI  - Anharmonicity and thermal expansion in crystalline germanium.

PMID- 15263267
TI  - High-temperature EXAFS study of solid and liquid rhodium.

PMID- 15263269
TI  - Solid and liquid short-range structure determined by EXAFS multiple-scattering
      data analysis.

PMID- 15263270
TI  - Pre-edge structure analysis of Ti K-edge polarized X-ray absorption spectra in
      TiO2 by full-potential XANES calculations.

PMID- 15263271
TI  - Theory of X-ray natural circular dichroism.

PMID- 15263272
TI  - Estimation of uncertainties in XAFS data.

PMID- 15263273
TI  - Rapid single- and multiple-scattering EXAFS Debye-Waller factor calculations on
      active sites of metalloproteins.

PMID- 15263274
TI  - Correction of XAFS amplitude distortions caused by the thickness effect.

PMID- 15263276
TI  - APEX: cross-platform analysis program for EXAFS.

PMID- 15263275
TI  - Practical regularization methods for analysis of EXAFS spectra.

PMID- 15263277
TI  - A web-based library of XAFS data on model compounds.

PMID- 15263278
TI  - DV-Xalpha MO approach to Zn K-XANES spectra of zinc aqueous solution.

PMID- 15263279
TI  - Determination of two- and three-body correlation functions in ionic solutions by
      means of MD and EXAFS investigations.

PMID- 15263280
TI  - EXAFS and principal component analysis: a new shell game.

PMID- 15263281
TI  - Dehydration processes for lanthanoid(III) chrolanilate complexes studied by
      EXAFS.

PMID- 15263282
TI  - L3 and M4,5 absorption edges of intermediate valent cerium unravelled by resonant
      photoemission and resonant Auger spectroscopy.

PMID- 15263283
TI  - Solving the structure of nanoparticles by multiple-scattering EXAFS analysis.

PMID- 15263284
TI  - Real space approach to thermal factors in EXAFS for strong anharmonic systems.

PMID- 15263285
TI  - The regular approach for identifying the atomic displacements in ABO3 crystals
      and its application to high-temperature phases of KNbO3.

PMID- 15263286
TI  - Error analysis of EXAFS measurements.

PMID- 15263287
TI  - Atomic background in 4p elements.

PMID- 15263288
TI  - Separation of weak EXAFS signal from atomic background in Br and Rb samples.

PMID- 15263289
TI  - Theoretical study of cluster size effects on X-ray absorption and resonant X-ray
      emission spectra in d and f electron systems.

PMID- 15263290
TI  - XAFS Debye-Waller factors in aqueous Cr+3 from molecular dynamics.

PMID- 15263291
TI  - Recursion method for multiple-scattering XAFS Debye-Waller factors.

PMID- 15263292
TI  - L-edge XANES of 3d-transition metals.

PMID- 15263293
TI  - Approximate spherical wave thermal factors in XAFS.

PMID- 15263294
TI  - A fully relativistic theory for magnetic EXAFS - formalism and applications.

PMID- 15263295
TI  - Path-integral effective-potential theory for EXAFS cumulants compared with the
      second-order perturbation.

PMID- 15263296
TI  - Interpreting atomic resolution EELS spectra using multiple scattering theory.

PMID- 15263297
TI  - DAFS experiments for phase-sensitive determination of local structure around Zr
      in Co/Zr multilayers.

PMID- 15263298
TI  - DAFS analysis of magnetite.

PMID- 15263299
TI  - Reliability of structural parameters determined from DAFS data using the
      iterative dispersion integral algorithm.

PMID- 15263300
TI  - Edge separation using diffraction anomalous fine structure.

PMID- 15263301
TI  - Direct measurement of valence charge asymmetry in GaAs using X-ray standing
      waves.

PMID- 15263302
TI  - XANES studies of Fe-bearing glasses.

PMID- 15263304
TI  - Micro-XAS studies with sorbed plutonium on tuff.

PMID- 15263303
TI  - XAFS and micro-XAFS at the PNC-CAT beamlines.

PMID- 15263305
TI  - Micro-beam X-ray absorption and fluorescence spectroscopies at GSECARS: APS
      beamline 13ID.

PMID- 15263306
TI  - Micro-XANES by EPMA spectrometer.

PMID- 15263307
TI  - Spectromicroscopy of Mn distributions in micronodules produced by
      biomineralization.

PMID- 15263308
TI  - Structure of single selenium chains confined in nanochannels of zeolites: a
      polarized X-ray absorption study.

PMID- 15263309
TI  - The observation of unusual polarization dependence in single-crystal vanadium K
      edge spectra of [H2tmen][VO(malonato)2H2O].2H2O.

PMID- 15263311
TI  - XAFS studies of interfaces in MnSe/ZnTe superlattices.

PMID- 15263310
TI  - Polarized XAFS study of the atomic displacements and phase transitions in KNbO3.

PMID- 15263312
TI  - Electronic states of doped holes in La(2-x)SrxCuO4: a unique application of XAFS.

PMID- 15263313
TI  - Strong metal-to-ligand charge transfer bands observed in Ni K- and L-edge XANES
      of planar Ni complexes.

PMID- 15263314
TI  - Polarized Ni K- and L-edge and S K-edge XANES study of [Ni(III)(mnt)2]1-.

PMID- 15263315
TI  - High-quality energy-dispersive XAFS on the 1 s timescale applied to
      electrochemical and catalyst systems.

PMID- 15263316
TI  - X-ray absorption spectroscopy and electrochemistry on biological samples.

PMID- 15263317
TI  - Biological EXAFS at room temperature.

PMID- 15263318
TI  - TDXAS study of the conformational landscape of MbCO.

PMID- 15263319
TI  - Fe-heme structure and dynamics in Thr72 --> Ile mutant Scapharca inaequivalvis
      hemoglobin by X-ray absorption spectroscopy.

PMID- 15263320
TI  - EXAFS investigation of the interaction of hafnium and thorium with humic acid and
      Bio-Rex 70.

PMID- 15263321
TI  - Multiple K-edge XAS for the structural analysis of thiophenolate bridged
      heterotrinuclear complexes.

PMID- 15263322
TI  - A comparison of Bacillus cereus and Aeromonas hydrophilia Zn-beta-lactamases.

PMID- 15263323
TI  - Time-resolved energy-dispersive XAS studies of photoinduced electron transfer
      intermediates in electron donor-acceptor complexes.

PMID- 15263324
TI  - EXAFS studies of the novel iron(III) complexes with an N/S(Se) chromophore
      simulating ligand environment of the active site of nitrile hydratase.

PMID- 15263325
TI  - The penta-coordinated vanadium formed on binding of ADP-vanadate-Mg(II) to CF1
      ATPase functions as a transition-state inhibitor.

PMID- 15263326
TI  - Polarized XAS on vectorially oriented single monolayers of cytochrome c.

PMID- 15263327
TI  - Structural determination of Pb binding sites in Penicillium chrysogenum cell
      walls by EXAFS spectroscopy and solution chemistry.

PMID- 15263328
TI  - Studies of Fe(II) and Fe(III)-DNA complexes by XANES spectroscopy.

PMID- 15263330
TI  - EXAFS studies on the active site of purple acid phosphatase from sweet potato
      Ipomoea batatas.

PMID- 15263329
TI  - Proximity of calcium to the manganese cluster of the photosynthetic oxygen
      evolving complex determined from strontium XAFS.

PMID- 15263331
TI  - The assembling of a catalytic active copper site, in solution, followed by EXAFS.

PMID- 15263332
TI  - XAFS study of Fe- and Mn-promoted sulfated zirconia.

PMID- 15263333
TI  - XAFS analysis of unsupported MoS2 catalysts prepared by two methods.

PMID- 15263334
TI  - Following the reduction under H2 of supported cobalt catalysts through the L
      absorption edges.

PMID- 15263335
TI  - XAS structural and electronic investigation of a new type of catalyst: AlGaPON.

PMID- 15263336
TI  - In situ Ni K-edge XANES study of the reducibility of Ni in FCC catalysts.

PMID- 15263337
TI  - Pt L3-edge XANES studies about the hydrogen adsorption on small Pt particles.

PMID- 15263338
TI  - XAFS study of silver clusters in zeolites.

PMID- 15263339
TI  - X-ray absorption reveals surface structure of titanium dioxide nanoparticles.

PMID- 15263340
TI  - X-ray absorption spectroscopy of transition aluminas.

PMID- 15263341
TI  - Characterization of metal ion-implanted titanium oxide photocatalysts operating
      under visible light irradiation.

PMID- 15263342
TI  - Characterization and photocatalytic reactivities of Cr-HMS mesoporous molecular
      sieves.

PMID- 15263343
TI  - XAFS study of ytterbium complexes as new-type Lewis acid catalysts.

PMID- 15263344
TI  - EXAFS analysis of Pd atomic clusters.

PMID- 15263345
TI  - EXAFS and XANES study of the incorporation of Mn cations into a chabazite-like
      AlPO molecular sieve.

PMID- 15263346
TI  - Effect of rhodium modification on structures of sulfided Rh-Mo-K/Al2O3 catalysts
      studied by XAFS.

PMID- 15263347
TI  - XAS of electronic state correlations during the reduction of the bimetallic
      PtRe/Al2O3 system.

PMID- 15263348
TI  - Thermal decomposition of (NH4)2[PtCl6] - an in situ X-ray absorption spectroscopy
      study.

PMID- 15263349
TI  - XANES study of the support effect on the state of platinum catalysts.

PMID- 15263350
TI  - Structural properties of Zn2-2x(CuIn)xS2 (x <or= 1) solid solution thin films
      obtained by EXAFS.

PMID- 15263351
TI  - The optically active center of Er-doped Si produced by laser ablation.

PMID- 15263352
TI  - The structure of amorphous Si-Ni alloys.

PMID- 15263353
TI  - Improvement in the structural characterization of nanometer-scale metallic oxide.
      The Xas-Awaxs combined approach.

PMID- 15263354
TI  - EXAFS studies of KBr1-x(NO2)x mixed crystals.

PMID- 15263355
TI  - A quantitative in situ Fe K-XAFS study (T > 1270 K) on the oxidation degree of
      iron in (Mg1-xFex)1-deltaO.

PMID- 15263356
TI  - Local atomic ordering in bulk amorphous (GaSb)1-xGe2x.

PMID- 15263357
TI  - Growth and dissolution of CdS nanoparticles in glass.

PMID- 15263358
TI  - Extraction of phase fractions and compositions for bcc/fcc two-phase binary
      alloys from XANES data.

PMID- 15263359
TI  - Layer perfection in ultrathin MOVPE-grown InAs layers buried in GaAs(001) studied
      by X-ray standing waves and photoluminescence spectroscopy.

PMID- 15263360
TI  - XAFS study of rhombohedral ferroelectric PbHf0.9Ti0.1O3.

PMID- 15263361
TI  - Local structure in semiconductor superlattices and epilayers.

PMID- 15263362
TI  - Environment of Pr in fluorozirconate glasses: an XAFS and anomalous X-ray
      scattering study.

PMID- 15263363
TI  - Local structure of pre-alloyed Al/Y/SiCN nanopowders studied by XAS at the Al K
      edge using fluorescence yield detection.

PMID- 15263364
TI  - XAFS analysis of particle size effect on local structure in BaTiO3.

PMID- 15263365
TI  - Polarized XANES spectra of titanium dichalcogenides - experiment and theory.

PMID- 15263366
TI  - The effect of germanium on the Co-SiGe thin-film reaction.

PMID- 15263367
TI  - XAFS studies of Al/TiNx films on Si(100) at the Al K- and L3,2-edge.

PMID- 15263368
TI  - Co L3,2-edge and multi-detection channel XAFS studies of Co-Si interactions.

PMID- 15263369
TI  - XAFS studies of Rh nanostructures on porous silicon.

PMID- 15263370
TI  - Relationship between the electronic and local structure in BaBi1-xPbxO3 and Ba1
      xKxBiO3 perovskites.

PMID- 15263371
TI  - EXAFS study of Zr environment in amorphous precursors of Pb(Zr,Ti)O3.

PMID- 15263372
TI  - XMCD and magnetism of the ferrimagnetic system NaV6O11.

PMID- 15263373
TI  - XANES study of the electronic structure of molten germanium.

PMID- 15263374
TI  - Temperature/magnetization-induced distortions in the local structure of
      substituted LaMnO3.

PMID- 15263375
TI  - Local structures around Co and Mn ions in ZnO-based varistors.

PMID- 15263376
TI  - Local structure in crystalline and liquid tellurium probed by X-ray absorption
      spectroscopy.

PMID- 15263377
TI  - On the effect of ion implantation in the microstructure of GaN: an XAFS study.

PMID- 15263378
TI  - Nitrogen K-edge EXAFS measurements on Mg- and Si-doped GaN.

PMID- 15263379
TI  - Nitrogen K-edge NEXAFS measurements on group-III binary and ternary nitrides.

PMID- 15263380
TI  - Gallium K-edge EXAFS measurements on cubic and hexagonal GaN.

PMID- 15263381
TI  - XAFS study on RbC60.

PMID- 15263382
TI  - The local structure of ferroelectric Pb1-xGexTe.

PMID- 15263383
TI  - Bond lengths in semiconductor alloys.

PMID- 15263384
TI  - Local structures of dilute impurities in Si crystal studied by fluorescence XAFS.

PMID- 15263385
TI  - Thermally and optically induced spin transition effect on the structure of
      iron(II) polymeric complexes.

PMID- 15263386
TI  - XAFS studies of pyranonate and pyridinone metal(III) complexes.

PMID- 15263387
TI  - The effect of solvent on the structure of the transition metal complexes in
      solutions.

PMID- 15263388
TI  - Soft X-ray photochemistry at the L2,3-edges in K3[Fe(CN)6], [Co(acac)3] and
      [Cp2Fe][BF4].

PMID- 15263389
TI  - Radiation-induced degradation of polydiene sulfones as obtained by sulfur K-edge
      XANES.

PMID- 15263390
TI  - Time-resolved EXAFS investigations of the anodic dissolution of Mo.

PMID- 15263391
TI  - Local structure of chromium incorporated into electrodeposited nickel hydroxide
      films.

PMID- 15263392
TI  - In situ XAS of the reaction mechanism of lithium with tin-based composite oxide
      glass.

PMID- 15263393
TI  - Shape resonances and EXAFS scattering in the Pt L2,3 XANES from a Pt electrode.

PMID- 15263394
TI  - Acceleration of halogen-exchange reaction of lead(II) fluoride in organic
      solvent.

PMID- 15263395
TI  - Alkaline earth oxide nanoparticles as destructive absorbents for environmental
      toxins.

PMID- 15263396
TI  - High-temperature indium(III) solutions.

PMID- 15263397
TI  - Evolution of the metal coordination sphere in homoleptic amido uranium compounds.

PMID- 15263398
TI  - Identification of Cr species at the aqueous solution-hematite interface after
      Cr(VI)-Cr(III) reduction using GI-XAFS and Cr L-edge NEXAFS.

PMID- 15263399
TI  - GIXAFS study of Fe3+ sorption and precipitation on natural quartz surfaces.

PMID- 15263400
TI  - Grazing-incidence XAFS studies of aqueous Zn(II) on sapphire single crystals.

PMID- 15263401
TI  - XANES studies at the Al K-edge of aluminium-rich surface phases in the soil
      environment.

PMID- 15263402
TI  - Local structure around europium ions doped in borate glasses.

PMID- 15263403
TI  - Grazing-incidence XAFS investigations of Cu(II) sorption products at alpha-Al2O3
      water and alpha-SiO2-water interfaces.

PMID- 15263404
TI  - Stability of copper sulfide in a contaminated soil.

PMID- 15263405
TI  - Investigation of the local chemical interactions between Hg and self-assembled
      monolayers on mesoporous supports.

PMID- 15263406
TI  - XAFS study of adsorbed and mineral forms of phosphate.

PMID- 15263407
TI  - Using zone plates for X-ray microimaging and microspectroscopy in environmental
      science.

PMID- 15263408
TI  - XAFS and XSW study of the distribution of Pb(II) sorbed to biofilms on alpha
      Al2O3 and alpha-FeOOH surfaces.

PMID- 15263409
TI  - Combined EXAFS and FTIR investigation of sulfate and carbonate effects on Pb(II)
      sorption to goethite (alpha-FeOOH).

PMID- 15263410
TI  - Utility of EXAFS in characterization and speciation of mercury-bearing mine
      wastes.

PMID- 15263411
TI  - Adsorption of Au ferrihydrites using Au-LIII edge XAFS spectroscopy.

PMID- 15263412
TI  - EXAFS studies of the chemical state of lead and copper in corrosion products
      formed on the brass surface in potable water.

PMID- 15263413
TI  - Manganese speciation in exhaust particulates of automobiles using MMT-containing
      gasoline.

PMID- 15263414
TI  - EXAFS and XANES characterization of sedimentary iron in the Gulf of Trieste (N.
      Adriatic).

PMID- 15263415
TI  - Evolution of sulfur during pyrolysis of petroleum kerogens.

PMID- 15263416
TI  - Floating sulfides: activating and poisoning surfaces.

PMID- 15263417
TI  - In situ chemical speciation of iron in estuarine sediments using XANES
      spectroscopy with partial least-squares regression.

PMID- 15263418
TI  - Characterization of sulfur in asphaltenes by sulfur K- and L-edge XANES
      spectroscopy.

PMID- 15263419
TI  - X-ray natural circular dichroism of gyrotropic crystals.

PMID- 15263420
TI  - XMCD at the Co K-edge in RCo2 intermetallics: influence of the rare earths.

PMID- 15263421
TI  - XMCD at the L2,3-edges of Pt in ordered TPt3 alloys (T = Cr, Mn, Co).

PMID- 15263422
TI  - The effect of the annealing temperature on the local distortion of
      La0.67Ca0.33MnO3 thin films.

PMID- 15263423
TI  - Scattering-angle dependence of the magnetic circular dichroism of resonant
      inelastic X-ray scattering.

PMID- 15263424
TI  - X-ray magnetic circular dichroism used to image magnetic domains.

PMID- 15263425
TI  - Hard X-ray MCD in GdNi5 and TbNi5 single crystals.

PMID- 15263426
TI  - Sum rule practice.

PMID- 15263427
TI  - Magnetic L-edge EXAFS of 3d elements: multiple-scattering analysis and spin
      dynamics.

PMID- 15263428
TI  - Magnetism of thin films and in Fe/Ni, Co/Fe bilayers on Cu(001).

PMID- 15263429
TI  - Investigation of the CeTX system by means of X-ray absorption spectroscopy:
      correlation with other data.

PMID- 15263430
TI  - Comparative investigation of CeNiSn2 isotype compounds by X-ray absorption
      spectroscopy.

PMID- 15263431
TI  - Zr site determination and origin of magnetic anisotropy in HDDR processed
      Nd2Fe14B-based magnets.

PMID- 15263432
TI  - Near-edge X-ray absorption and dichroism in amino acids.

PMID- 15263433
TI  - Magnetic EXAFS calculations for disordered alloys.

PMID- 15263434
TI  - Structural changes of Fe precipitates in annealed Fe-Al2O3 films.

PMID- 15263435
TI  - Influence of cations vacancies on the K and LIII Zn edges of spinel-related
      compounds.

PMID- 15263436
TI  - Study of the effects of Ca sulfonate on antiwear film formation by X-ray
      absorption spectroscopy using synchrotron radiation.

PMID- 15263437
TI  - EXAFS investigation of nanoparticles produced in a thermal plasma process.

PMID- 15263438
TI  - XAFS and XRD studies on local and long-range structures of mechanically alloyed
      AlxTi1-x solid solutions.

PMID- 15263439
TI  - Structural studies on colloidal tetraalkylammonium manganese oxides.

PMID- 15263440
TI  - Electronic structure of Ni3Al and Ni3Ga alloys.

PMID- 15263441
TI  - XAFS study on D+ irradiated Si surface.

PMID- 15263442
TI  - EXAFS study of Tb-doped silica xerogels.

PMID- 15263443
TI  - Study of the interaction between antiwear, extreme pressure and rust inhibitor
      agents in the formation of protective films by X-ray absorption spectroscopy.

PMID- 15263444
TI  - XAS investigation on polyvalent cation intercalation in V2O5 aerogels.

PMID- 15263445
TI  - Structural transition in epitaxial Co/Cr multilayers as studied by X-ray
      absorption spectroscopy.

PMID- 15263446
TI  - Local atomic structures of hematite nanoparticles studied with XAFS.

PMID- 15263447
TI  - Local structure and Tc suppression in Bi2Sr2Ca1-xYx(Cu1-yZny)2O8+delta
      superconductor at 1/8 doping.

PMID- 15263448
TI  - Structural disorder and the origin of high-Tc suppression in La1.875Ba0.125CuO4.

PMID- 15263449
TI  - Why does Ni suppress superconductivity in La1.85Sr0.15Cu1-yNiyO4?

PMID- 15263450
TI  - A structural model for the CaLaBaCu3O7 superconductor from a detailed EXAFS
      study.

PMID- 15263451
TI  - EXAFS studies of (Pb,Cd)1212 phase superconductor and (Bi,Cd)1212 phase compound.

PMID- 15263452
TI  - The local structure of the CuO2 plane in Nd2-xCexCuO4-delta: an X-ray absorption
      study.

PMID- 15263453
TI  - Real-space multiple-scattering analysis of Ag L1- and L3-edge XANES spectra of
      Ag2O.

PMID- 15263454
TI  - Evolution of long-range and short-range order in La0.67Ca0.33MnO3-delta during
      solid-state transformation using high-energy ball milling.

PMID- 15263455
TI  - Spatial cross-over of polarons across the CMR transition in La0.75Ca0.25MnO3
      system.

PMID- 15263456
TI  - XAFS study on Eu@C60.

PMID- 15263457
TI  - Tautomeric structure of N-salicylideneaniline derivatives studied by soft X-ray
      absorption spectroscopy and X-ray photoelectron spectroscopy.

PMID- 15263458
TI  - The early stages of growth of Mn deposited at room temperature on Ag(001) studied
      by Mn K-edge SEXAFS and Mn L2,L3-edges XAS.

PMID- 15263459
TI  - Adsorption structures of alkanethiols self-assembled monolayers on the Cu(100)
      surface studied by S-K EXAFS and C-K NEXAFS spectroscopies.

PMID- 15263460
TI  - Local structures of (Ge4/Si4)5 monolayer strained-layer supperlattice probed by
      fluorescence XAFS.

PMID- 15263461
TI  - Self-assembled monolayers of 4-aminothiophenol on copper surfaces studied by
      grazing-incidence X-ray absorption spectroscopy.

PMID- 15263462
TI  - NEXAFS studies on the structure of perfluoroalkyl carbonic acid Langmuir Blodgett
      films.

PMID- 15263463
TI  - Maintaining and improving the quality of published XAFS data: a view from the UK
      XAFS user group.

PMID- 15263464
TI  - 'Atomic' XAFS as a probe of electronic structure.

PMID- 15263465
TI  - Effective escape depth of photoelectrons for hydrocarbon films in total electron
      yield measurement as C K-edge.

PMID- 15263466
TI  - SR Conference Proceedings and JSR.

PMID- 15263467
TI  - Synchrotron radiation - early history.
AB  - The scientific history of the work that led to the prediction and observation of
      synchrotron radiation goes back more than a century. This paper is a summary of
      that history.

PMID- 15263468
TI  - A prospect and retrospect - the Japanese case.
AB  - This paper has been published previously in the November 1997 issue of this
      journal, which commemorated 50 Years of SR [Sasaki (1997), J. Synchrotron Rad. 4,
      359-364].The early through recent history of synchrotron radiation research in
      Japan, since the initial efforts in 1962, is reviewed. Following a period of
      parasitic use of an electron synchrotron, Japanese users attempted to build a
      storage ring as a dedicated soft X-ray source, which was completed in 1974. It
      opened up a new era of second-generation synchrotron radiation research. The
      Photon Factory, a dedicated X-ray source commissioned in 1982, provided a much
      wider research area as well as a number of technical innovations, among which
      insertion devices brought the further prospect of significant improvements in the
      properties of sources. As a consequence, the new concept of a light source
      oriented towards full exploitation of insertion devices, or the idea of a third
      generation source, was created. The motivations and developments which led to
      Spring-8, a third-generation Japanese X-ray source that is currently being
      commissioned, will be reviewed briefly.

PMID- 15263469
TI  - How X-ray Diffraction with Synchrotron Radiation Got Started.
AB  - The need to record low-angle-scattering X-ray fibre diagrams from muscle with
      millisecond time resolution drove the use of synchrotron radiation as an X-ray
      light source. The first smudgy diffraction patterns were obtained from a slice of
      insect flight muscle. Out of this grew the EMBL Outstation at DESY.

PMID- 15263470
TI  - The advanced photon source: performance and results from early operation.
AB  - The Advanced Photon Source at Argonne National Laboratory is now providing
      researchers with high-brilliance undulator radiation from below 1 keV to beyond
      100 keV. All technical facilities and components are operational and have met
      design specifications. Fourteen research teams, with responsibility for 40
      beamlines on the APS experiment hall floor, are currently installing beamline
      instrumentation or actively taking data. An overview is presented for the first
      operational year of the Advanced Photon Source. Emphasis is on the performance of
      accelerators and insertion devices, as well as early scientific results and
      future plans.

PMID- 15263471
TI  - Present status of the pohang light source.
AB  - The Pohang Light Source (PLS), the first large-scale accelerator complex in
      Korea, is a national users facility for basic and applied science research using
      synchrotron radiation. It consists of a 2 GeV linac as a full-energy injector and
      a low-emittance storage ring. The PLS linac is 150 m long with eleven 80 MW
      klystrons for a high accelerating gradient; the storage ring has the TBA-lattice
      with 12 super-periods and a 280 m circumference. Since the accelerators were
      commissioned in December 1994, the annual operation time exceeded 4600 h in 1996,
      and the user service time is expected to reach 3500 h in 1997. The facility was
      opened to general users in 1995 with two beamlines. Six beamlines are now
      operating: white-beam, NIM for ARUPS and gas-phase, photoemission spectroscopy,
      EXAFS, X-ray diffraction and lithography. Our long-term plan is to construct
      three new beamlines every year.

PMID- 15263472
TI  - SPring-8 Program.
AB  - SPring-8 is a third-generation synchrotron radiation source operating in the soft
      and hard X-ray region. It consists of an injector linac of 1 GeV, a booster
      synchrotron of 8 GeV and a storage ring with a natural emittance of 5.9 nm rad.
      The storage ring can accommodate 61 beamlines in total, and 26 of them are under
      construction. The project has been carried out jointly by JAERI and RIKEN and
      construction of the facility started in 1991. Commissioning of the injector linac
      was started in August 1996 and an 8 GeV electron beam was injected into the
      storage ring in March 1997. The first synchrotron radiation from a bending magnet
      was observed at the front end of the beamline on 25 March and radiation from an
      undulator was observed on 23 April. On-beam testing of seven beamlines, four of
      them from in-vacuum undulators and three from bending magnets, started in July.
      The maximum stored current is currently fixed at 20 mA and the lifetime at
      maximum current is longer than 20 h. The dedication is scheduled for October
      1997.

PMID- 15263473
TI  - Synchrotron radiation sources - present capabilities and future directions.
AB  - Many of the more than 40 operational light sources around the world have achieved
      performance levels that exceed initial design goals. These accomplishments are
      reviewed, along with concepts and proposals for sources with performance levels
      exceeding those of present sources. These include storage rings with lower
      electron-beam emittance than present third-generation rings and free-electron
      lasers (FELs). It now appears that the highest performance sources will be based
      on linacs rather than storage rings. This is because emittance originates
      differently and scales differently with electron energy for rings and linacs, so
      that the lowest electron-beam emittance can be achieved in high-energy linacs
      equipped with high-brightness electron sources. Such electron beams can be used
      to provide X-ray beams with very high brightness and coherence in sub-picosecond
      pulses in a single pass through a small-gap short-period undulator by spontaneous
      emission, and with even higher beam brightness and coherence by stimulated
      coherent emission in an FEL. Designs for such FEL sources, and associated
      research and development, are underway at several laboratories.Work supported by
      the US Department of Energy, Office of Basic Energy Sciences, contract DE-AC03
      76SF00515.

PMID- 15263474
TI  - Synchrotron light sources and recent developments of accelerator technology.
AB  - The main aim of the next-generation synchrotron radiation sources is to provide
      diffraction-limited undulator radiation in the 0.1-4 nm range with an average
      power of 10-1000 W and monochromaticity of 10(-3)-10(-4). A review of new
      accelerator technologies that could be used for the construction of such types of
      synchrotron radiation sources is given.

PMID- 15263475
TI  - Development of synchrotron radiation storage rings.
AB  - Many third-generation light sources have been commissioned over the past ten
      years, and the soundness of the principal design concepts has been well
      recognized through experiences at these facilities. Also, technological
      developments concerning third-generation light sources have been remarkable. With
      the emittance and current of the beams far exceeding the previous levels,
      stability requirements of the beams have become much more stringent. In this
      report the present status of light sources, operational and projected, is
      summarized, and developments and future prospects of synchrotron radiation
      storage rings in view of accelerator physics and technology are reviewed.

PMID- 15263476
TI  - Present Status of SPring-8 Insertion Devices.
AB  - According to the general policy, namely, the pursuit of pure radiation without
      any unreasonable heat load, the construction of various insertion devices has
      been scheduled at SPring-8. Most of them are of the in-vacuum type, which makes
      it possible to realize short-period devices, so that the fundamental of undulator
      radiation may be obtained in the hard X-ray region. In addition, undulator
      radiation in the soft X-ray range down to 100 eV is available by introducing
      helical or figure-8 devices having low on-axis power density, which is very
      beneficial for the optics, gratings or mirrors. A brief overview of the insertion
      devices at SPring-8 is presented with the initial commissioning results.

PMID- 15263477
TI  - APS Insertion Devices: Recent Developments and Results.
AB  - The Advanced Photon Source (APS) now has a total of 23 insertion devices (IDs).
      Over two-thirds of them are installed on the storage ring. The installed devices
      include 18, 27 and 55 mm-period undulators; an 85 mm-period wiggler; a 16 cm
      period elliptical multipole wiggler; and many 33 mm-period undulators. Most of
      the IDs occupy storage-ring straight sections equipped with 8 mm vertical
      aperture vacuum chambers. All of the IDs were measured magnetically at the APS
      and, in most cases, underwent a final magnetic tuning in order to minimize
      variation in the various integrals of the field through the ID over the full gap
      range. Special shimming techniques to correct magnetic field parameters in
      appropriate gap-dependent ways were developed and applied. Measurements of the
      closed-orbit distortion as a function of the ID gap variation have been
      completed, and results are in a good agreement with magnetic measurements.
      Spectral diagnostics of the ID radiation, including measurements of the absolute
      spectral flux, brilliance and polarization, show excellent agreement between
      calculated and measured results. Studies of the sensitivity of IDs to radiation
      exposure and measurements of the dose rate received by the IDs are in progress.

PMID- 15263478
TI  - The ESRF Insertion Devices.
AB  - The European Synchrotron Radiation facility is presently operating 47 segments of
      insertion devices (IDs). A record brilliance of 1 x 10(20) photons s(-1) (0.1%
      bandwidth)(-1) mm(-2) mrad(-2) has been reached. Almost all devices are built
      with permanent magnets with or without iron pole pieces. They have been
      mechanically and magnetically designed and field-measured in house. Multipole
      shimming has been applied to all devices to remove the integrated dipole and
      higher-order multipole fields, thereby reducing the interaction between the IDs
      and the stored beam. For all undulators, the field errors have been corrected
      further using spectrum shimming in order to achieve ideal spectral brilliance on
      all harmonic numbers from 1 to 15. A significant effort has been made to optimize
      the magnet terminations for both field-integral correction and phasing. A phasing
      scheme of the undulator segments has been developed which allows the independent
      manufacture and operation of individual segments. Several designs for undulator
      phasing are presented, together with a comparison between hybrid and pure
      permanent-magnet technology. A new type of variable-polarization helical
      undulator is presented.

PMID- 15263479
TI  - Advanced capabilities for future light sources.
AB  - Methods to extend the capabilities of light sources beyond those available at the
      current generation synchrotron radiation sources based on undulators in electron
      storage rings are discussed. Taking advantage of the radiation-particle
      interaction and/or the availability of high-power ultrashort optical lasers, it
      is possible to develop sources with higher brightness, smaller temporal
      resolution, or higher photon energy. This paper is a summary of some of these
      schemes, with an emphasis on new ideas rather than on a comprehensive review.

PMID- 15263480
TI  - High-energy inelastic-scattering beamline for electron momentum density study.
AB  - The advent of synchrotron radiation sources for well polarized and high-energy X
      rays offers new opportunities for exploiting Compton scattering spectroscopy as a
      tool for investigating the electronic and magnetic structures of materials.
      Recent high-resolution Compton scattering experiments show the unique capability
      for the study of Fermiology-related issues and electron-electron correlation
      effects. Intense, high-energy and circularly polarized X-ray sources have
      improved magnetic Compton scattering spectroscopy from the point of statistical
      accuracy and momentum resolution. As a next advance, a high-energy inelastic
      scattering beamline dedicated to Compton scattering spectroscopies is being
      constructed at SPring-8. The light source is an elliptic multipole wiggler with a
      periodic length of 12 cm. The beamline includes two experimental stations: one is
      for high-resolution spectroscopy using 100-150 keV X-rays and the other is for
      magnetic Compton scattering experiments using circularly polarized 300 keV X
      rays. The use of such high-energy X-rays makes it possible to carry out
      experiments efficiently on samples including heavier elements, such as high-T(c)
      superconductors and 4f and 5f magnetic materials.

PMID- 15263481
TI  - ID14 'Quadriga', a Beamline for Protein Crystallography at the ESRF.
AB  - The ESRF undulator beamline ID14 'Quadriga' is dedicated to monochromatic
      macromolecular crystallography. Using two undulators with 23 mm and 42 mm periods
      and a minimum gap of 16 mm installed on a high-beta section, it will provide high
      brilliance X-ray beams at around 13.5 keV, as well as a wide tuneability between
      6.8 and 40 keV. Based on the Troika concept, this beamline has four
      simultaneously operating experimental stations: three side stations, EH1, EH2 and
      EH3, using thin diamond crystals, and an end station, EH4, with a fast-scan
      double-crystal monochromator. Station EH3 has a kappa-diffractometer, and an off
      line Weissenberg camera with a large 80 x 80 cm active area combined with a 2048
      x 2048 CCD detector. During data collection the image plates are placed and
      removed by a robot located inside the hutch using a cassette system. After data
      collection the image plates are scanned with an off-line drum scanner. Station
      EH4 is designed for MAD applications, including Xe K-edge anomalous experiments,
      and is equipped with a 2048 x 2048 CCD detector on a pseudo 2theta arm. A common
      graphical user interface and a database will be available to cover all aspects of
      data collection, including strategy optimization. First results on the
      performance of the optics elements and initial crystallographic results are
      presented.

PMID- 15263482
TI  - Trichromatic Concept at SPring-8 RIKEN Beamline I.
AB  - SPring-8 RIKEN beamline I has been designed and developed for structural biology
      research by the Institute of Physical and Chemical Research (RIKEN). The beamline
      consists of two experimental stations for protein crystallography and small-angle
      X-ray scattering. Both types of experiments can be carried out simultaneously,
      with dichromatic synchrotron radiation emitted from two coaxial undulators with
      vertical polarization. The branched beams are generated by a transparent diamond
      crystal. With synchrotron radiation, the multiple-wavelength anomalous-dispersion
      (MAD) method, which gives phases from a single anomalous scatterer, has been
      developed. Anomalous scattering contributes a small proportion of the diffraction
      intensity so that the accuracy of intensity data is important. The protein
      crystallography branch of RIKEN beamline I has been designed based on a
      'trichromatic concept' to optimize MAD data collection. This concept requires the
      quasi-simultaneous collection, by use of a 'trichromator', of three intensity
      data sets at three different wavelengths from a single protein crystal without
      changing any settings. The main feature of the concept is the minimization of
      systematic errors in the measurement of anomalous diffraction for the MAD method.
      Initial commissioning of the beamline has provided three different monochromated
      undulator beams, which were successfully observed on the phosphor screen located
      at the near end of the trichromator.

PMID- 15263483
TI  - Focusing Optics for High-Energy X-ray Diffraction.
AB  - Novel focusing optical devices have been developed for synchrotron radiation in
      the energy range 40-100 keV. Firstly, a narrow-band-pass focusing energy-tuneable
      fixed-exit monochromator was constructed by combining meridionally bent Laue and
      Bragg crystals. Dispersion compensation was applied to retain the high momentum
      resolution despite the beam divergence caused by the focusing. Next,
      microfocusing was achieved by a bent multilayer arranged behind the crystal
      monochromator and alternatively by a bent Laue crystal. A 1.2 micro m-high line
      focus was obtained at 90 keV. The properties of the different set-ups are
      described and potential applications are discussed. First experiments were
      performed, investigating with high spatial resolution the residual strain
      gradients in layered polycrystalline materials. The results underline that
      focused high-energy synchrotron radiation can provide unique information on the
      mesoscopic scale to the materials scientist, complementary to existing techniques
      based on conventional X-ray sources, neutron scattering or electron microscopy.

PMID- 15263484
TI  - Instrumentation Developments for X-ray Linear and Circular Dichroism at the ESRF
      Beamline ID12A.
AB  - This paper reports on the performance of the instrumentation developed for the
      ESRF beamline ID12A, which is dedicated to spectroscopic applications requiring
      full control of the polarization at energies >/=2.0 keV. Emphasis is placed on
      the characterization of various optical components of the beamline and on
      problems associated with either the control or the conversion of the polarization
      state. A few examples have been selected to illustrate what sort of new
      spectroscopic information has already been obtained at the beamline. These
      include the comparison of X-ray magnetic dichroism spectra recorded with linear
      or circular polarization and the very first detection of X-ray natural circular
      dichroism in single crystals known to exhibit a very large non-linear
      susceptibility at optical wavelengths.

PMID- 15263485
TI  - Graded X-ray Optics for Synchrotron Radiation Applications.
AB  - Using X-ray diffractometry and spectral measurements, the structure and
      properties of graded X-ray optical elements have been examined. Experimental and
      theoretical data on X-ray supermirrors, which were prepared by the magnetron
      sputtering technique using precise thickness control, are reported. Measurements
      on graded aperiodic Si(1-x)Ge(x) single crystals, which were grown by the
      Czochralski technique, are also presented. The lattice parameter of such a
      crystal changes almost linearly with increasing Ge concentration. The
      measurements indicate that Si(1-x)Ge(x) crystals with concentrations up to 7 at.%
      Ge can be grown with a quality comparable to that of pure Si crystals.

PMID- 15263486
TI  - Application of a Varied-Line-Spacing Grating in a High-Performance Soft X-ray
      Monochromator.
AB  - The design and experimental evaluation of a high-resolution varied-line-spacing
      grating monochromator constructed at the Photon Factory are described. Various
      applications of a varied-line-spacing grating in a high-performance soft X-ray
      monochromator are discussed.

PMID- 15263487
TI  - A Pixel-Array Detector for Time-Resolved X-ray Diffraction.
AB  - An integrating pixel-array detector for recording time-resolved X-ray diffraction
      measurements on microsecond timescales has been designed and tested as a 4 x 4
      pixel prototype. Operational characteristics and radiation tolerance are
      discussed. A 100 x 92 array with 151.2 micro m square pixels is currently under
      construction.

PMID- 15263488
TI  - Development of a MicroStrip Gas Chamber as a Time-Resolved Area Detector.
AB  - A two-dimensional microstrip gas chamber (MSGC) has been developed with a 10 cm
      square detection area and an ultrafast read-out system. The MSGC was made using
      multi-chip module (MCM) technology, and has a very thin substrate of 17 micro m
      and many anodes and back strips, both with 200 micro m pitches. The new read-out
      system, in which the hit addresses of the electrodes were sequentially encoded to
      the hit positions by a synchronous clock, handles data rates of up to 10(7)
      events s(-1) from MSGCs. This enables the acquisition of fast and sequential
      digital images. Furthermore, since the MSGC is a real photon-counting detector,
      the timing of the photons, to an accuracy of a few tens of nanoseconds, and
      energy can be recorded. Here, the performance of the MSGC system as a real-time
      area detector is reported, and the abilities of this system are discussed.

PMID- 15263489
TI  - One- and Two-Coordinate Detectors in BINP.
AB  - One- and two-coordinate detectors with proportional chambers developed at the
      Budker Institute of Nuclear Physics (BINP) are presented. The parallax-free 10
      MHz one-coordinate OD-3.1 and OD-3.2 detectors are used in synchrotron radiation
      powder diffraction and SAXS experiments. The two-coordinate DED-3 detector with a
      multiwire proportional chamber (MWPC) is used in Laue diffraction. The latest
      modification of this detector, DED-5, with a working area of 384 x 384 mm, is
      briefly described. The micro-strip detector prototype MSGC-100 has passed test
      synchrotron radiation experiments and the next modification (MSGC-500), with 500
      channels for high energy, is under construction. The one-coordinate MWPC OD-160
      detector, with an angle aperture of 160 degrees and a count rate of 3.3 GHz, is
      under construction. It will be used for high-resolution powder diffraction. Two
      types of gas chamber will be used: L for low energies (5-30 keV) and H for high
      energies (30-70 keV). A 16 degrees section with an H-chamber has been produced
      and tested on the synchrotron radiation beamline.

PMID- 15263491
TI  - Avalanche Photodiodes as Fast X-ray Detectors.
AB  - An avalanche photodiode (APD) detector provides a sub-nanosecond time resolution
      and an output rate of more than 10(8) counts s(-1) of synchrotron X-rays.
      Moreover, the APD has the advantage of low noise. A review of recent developments
      of detectors using APD devices designed for X-ray experiments is presented in
      this paper. One of the detectors has an excellent time response of 100 ps
      resolution and a narrow width on its response function, 1.4 ns at 10(-5) maximum.
      The other consists of a stack of four diodes and has a transmission structure.
      The stacked detector improved the efficiency for X-rays, e.g. 55% at 16.53 keV.
      The output rates reached more than 10(8) counts s(-1) per device.

PMID- 15263490
TI  - High-Resolution High-Count-Rate X-ray Spectroscopy with State-of-the-Art Silicon
      Detectors.
AB  - For the European X-ray multi-mirror (XMM) satellite mission and the German X-ray
      satellite ABRIXAS, fully depleted pn-CCDs have been fabricated, enabling high
      speed low-noise position-resolving X-ray spectroscopy. The detector was designed
      and fabricated with a homogeneously sensitive area of 36 cm(2). At 150 K it has a
      noise of 4 e(-) r.m.s., with a readout time of the total focal plane array of 4
      ms. The maximum count rate for single-photon counting was 10(5) counts s(-1)
      under flat-field conditions. In the integration mode more than 10(9) counts s(-1)
      can be detected at 6 keV. Its position resolution is of the order of 100 micro m.
      The quantum efficiency is higher than 90% from carbon K X-rays (277 eV) up to 10
      keV. New cylindrical silicon drift detectors have been designed, fabricated and
      tested. They comprise an integrated on-chip amplifier system with continuous
      reset, on-chip voltage divider, electron accumulation layer stabilizer, large
      area, homogeneous radiation entrance window and a drain for surface-generated
      leakage current. At count rates as high as 2 x 10(6) counts cm(-2) s(-1), they
      still show excellent spectroscopic behaviour at room-temperature operation in
      single-photon detection mode. The energy resolution at room temperature is 220 eV
      at 6 keV X-ray energy and 140 eV at 253 K, being achieved with Peltier coolers.
      These systems were operated at synchrotron light sources (ESRF, HASYLAB and NLS)
      as X-ray fluorescence spectrometers in scanning electron microscopes and as ultra
      low noise photodiodes. The operation of a multi-channel silicon drift detector
      system is already foreseen at synchrotron light sources for X-ray holography
      experiments. All systems are fabricated in planar technology having the detector
      and amplifiers monolithically integrated on high-resistivity silicon.

PMID- 15263492
TI  - High-Resolution X-ray Diffraction of Muscle Using Undulator Radiation from the
      Tristan Main Ring at KEK.
AB  - High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.High
      resolution X-ray diffraction studies on striated muscle fibres were performed
      using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba,
      Japan. The performance of the undulator, along with an example experiment which
      exploited the unique characteristics of undulator radiation, are reported. The
      vertical divergence angle of the first harmonic of the undulator was
      approximately 10 micro rad under 8 GeV multi-bunch operating conditions and the
      peak photon flux density was estimated to be approximately 3 x 10(16) photons s(
      1) mrad(-2) (0.1% bandwidth)(-1) (10 mA)(-1). The well collimated X-ray beam from
      the undulator made it possible to resolve clearly, with high angular resolution (
      approximately 700 nm), the closely spaced diffraction peaks on the meridional
      axis in the X-ray patterns arising from the thick filaments of a striated muscle
      under static conditions. By fitting the meridional intensity pattern, a model for
      the molecular arrangement of the constituent proteins in the thick filaments is
      proposed. These studies of muscle demonstrate the promise of undulator radiation
      from third-generation sources for high-resolution diffraction studies.

PMID- 15263493
TI  - Experiments with very high energy synchrotron radiation.
AB  - The use of synchrotron radiation with very high photon energies has become
      possible only with the latest generation of storage rings. All high-electron
      energy synchrotron sources will have a dedicated program for the use of very high
      photon energies. The high-energy beamline ID15 at the ESRF was the first beamline
      built and dedicated to this purpose, and it has now been in user operation for
      more than three years. The useful energy range of this beamline is 30-1000 keV
      and the superconducting insertion device for producing the highest attainable
      photon energies is described in detail. The techniques most often used today are
      diffraction and Compton scattering; an overview of the most important experiments
      is given. Both techniques have been used in the investigation of magnetic
      systems, and, additionally, the high resolution in reciprocal space, which can be
      achieved in diffraction, has led to a series of applications. Other fields of
      research are addressed, and attempts to indicate possible future research areas
      of high-energy synchrotron radiation are made.

PMID- 15263494
TI  - Spectroscopic Techniques using Synchrotron Radiation and Free-Electron and
      Conventional Lasers.
AB  - Considerable progress in the investigation of the electronic and vibrational
      properties of atoms, molecules, materials, surfaces and interfaces has been
      achieved by combining different photon sources of complementary characteristics.
      In this paper some experimental results obtained recently at LURE by using two
      synchronized sources, such as the IR free-electron laser (FEL) CLIO, the VUV
      storage ring FEL, synchrotron radiation and table lasers, are presented. Using
      CLIO synchronized with a YAG laser allows the investigation of the vibrational
      properties of adsorbed species by the non-linear optical technique of visible-IR
      sum (difference) frequency generation, as shown for the adsorption of hydrogen on
      platinum in the electrochemical environment. The second result reported here
      relates to the study of the intersubband stimulated emission in GaAs/GaAlAs
      quantum wells by pump-probe experiments using the two-colour configuration of
      CLIO. The combination of a mode-locked Ar(+) laser and synchrotron radiation has
      been used for investigations in a pump-probe arrangement of the ionization of Xe
      atoms via the resonant state Xe* 5p(5)5d [3/2](1). The final example is a time
      resolved core-level spectroscopy study of photoexcited Si(111) 2 x 1 surfaces by
      using a combination of the naturally synchronized UV storage ring laser and
      synchrotron radiation.

PMID- 15263495
TI  - The Soft X-ray Scanning Photoemission Microscopy Project at SRRC.
AB  - The Synchrotron Radiation Research Center (SRRC) and the Institute of Atomic and
      Molecular Sciences (IAMS) have initiated a project to construct a scanning
      photoelectron spectromicroscopy end station at SRRC (SRRC-SPEM). High-brightness
      soft X-rays will be provided by the U5 undulator beamline. Zone-plate-based soft
      X-ray optics will be used to focus the beam to form the microprobe. A
      hemispherical sector analyser with multichannel detection capability will collect
      the photoelectrons. A total of up to 32 images can be acquired concurrently. The
      apparatus is also equipped with a sample distribution system for in situ sample
      preparation and characterization in conjunction with other surface spectroscopic
      techniques.

PMID- 15263496
TI  - From first-order coherence to higher-order coherence of synchrotron radiation.
AB  - The difference between first-order and second-order coherence of synchrotron
      radiation is discussed in relation to how they can be measured and how they
      affect the noise characteristics of future free-electron lasers.

PMID- 15263497
TI  - Phase-Contrast Tomographic Imaging Using an X-ray Interferometer.
AB  - Apparatus for phase-contrast X-ray computed tomography using a monolithic X-ray
      interferometer is presented with some observational results for human breast
      tissues. Structures characteristic of the tissues were revealed in the phase
      contrast tomograms. The procedure of image analysis consists of phase retrieval
      from X-ray interference patterns and tomographic image reconstruction from the
      retrieved phase shift. Next, feasibility of phase-contrast imaging using a two
      crystal X-ray interferometer was studied aiming at in vivo observation in the
      future. In a preliminary study, the two-crystal X-ray interferometer was capable
      of generating fringes of 70% visibility using synchrotron X-rays.

PMID- 15263498
TI  - X-ray Holography for Structural Imaging.
AB  - X-ray atomic resolution holography is a new method for direct evaluation of three
      dimensional electron density distribution in solids. The practical implementation
      of the multiple-energy technique on a synchrotron radiation source as well as
      image reconstruction from the experimental data are described. Holograms at
      several different energies were processed together to suppress twin images and
      artifacts from long-range-order effects in the experimental data sets.
      Reconstructed images of copper atoms in Cu(2)O crystals are presented.

PMID- 15263499
TI  - Synchrotron Radiation Lithography for Manufacturing Integrated Circuits Beyond
      100 nm.
AB  - Extreme ultraviolet lithography is a powerful tool for printing features of 0.1
      micro m and below; in Japan and the USA there is a growing tendency to view it as
      the wave of the future. With Schwarzschild optics, replication of a 0.05 micro m
      pattern has been demonstrated in a 25 micro m square area. With a two-aspherical
      mirror system, a 0.15 micro m pattern has been replicated in a ring slit area of
      20 mm x 0.4 mm; a combination of this system with illumination optics and
      synchronized mask and wafer stages has enabled the replication of a 0.15 micro m
      pattern in an area of 10 mm x 12.5 mm. Furthermore, in the USA, the Sandia
      National Laboratory has succeeded in fabricating a fully operational NMOS
      transistor with a gate length of 0.1 micro m. The most challenging problem is the
      fabrication of mirrors with the required figure error of 0.28 nm. However, owing
      to advances in measurement technology, mirrors can now be made to a precision
      that almost satisfies this requirement. Therefore, it is time to move into a
      rapid development phase in order to obtain a system ready for practical use by
      the year 2004. In this paper the status of individual technologies is discussed
      in light of this situation, and future requirements for developing a practical
      system are considered.

PMID- 15263500
TI  - Medical applications with synchrotron radiation in Japan.
AB  - In Japan, various medical applications of synchrotron X-ray imaging, such as
      angiography, monochromatic X-ray computed tomography (CT), radiography and
      radiation therapy, are being developed. In particular, coronary arteriography
      (CAG) is quite an important clinical application of synchrotron radiation. Using
      a two-dimensional imaging method, the first human intravenous CAG was carried out
      at KEK in May 1996; however, further improvements of image quality are required
      in clinical practice. On the other hand, two-dimensional aortographic CAG
      revealed canine coronary arteries as clearly as those on selective CAG, and
      coronary arteries less than 0.2 mm in diameter. Among applications of synchrotron
      radiation to X-ray CT, phase-contrast X-ray CT and fluorescent X-ray CT are
      expected to be very interesting future applications of synchrotron radiation. For
      actual clinical applications of synchrotron radiation, a medical beamline and a
      laboratory are now being constructed at SPring-8 in Harima.

PMID- 15263501
TI  - A compact superconducting ring as a radiation source for X-ray crystallography.
AB  - A compact superconducting storage ring installed at Ritsumeikan University is
      operated at an electron-beam energy of 0.575 GeV and an initial beam current of
      300 mA. The radius of the circular electron orbit is as small as 0.5 m,
      suggesting that the radiation emitted contains short-wavelength components. With
      an imaging plate as a detector, X-ray precession diffraction patterns were
      recorded for organic single crystals within a reasonable period of time using
      radiation of wavelength 0.155 nm (8 keV) to 0.248 nm (5 keV). The use of the
      radiation in the structural study of organic crystals containing 3d metal atoms
      using the phenomena of anomalous scattering is described. If appropriately
      planned, X-ray diffraction and/or scattering experiments can be made at the
      compact ring without recourse to a large-scale ring.

PMID- 15263502
TI  - Design of a compact synchrotron light source for medical applications at NIRS.
AB  - A synchrotron light source dedicated to medical applications is required to be
      compact for installation in limited spaces at hospitals. The NIRS storage ring,
      with a circumference of 44.8 m, is designed to accelerate electrons up to 1.8 GeV
      and to store a beam of 400 mA. The ring is composed of superconducting bending
      magnets for downsizing. A beam of 300 MeV is injected into the ring from a
      microtron operated at an L-band RF frequency. There are two superconducting
      multipole wigglers with nine poles and a maximum field of 8 T, which can produce
      a photon flux of about 1.4 x 10(13) photons s(-1) mrad(-1) (0.1% bandwidth)(-1)
      at 33 keV used for coronary angiography.

PMID- 15263503
TI  - Design of a synchrotron radiation source at Tohoku University.
AB  - The construction of a third-generation light source has been proposed at Tohoku
      University. The emittance is 7.3 nm rad at the nominal beam energy, 1.5 GeV. The
      circumference is 194 m. The ring consists of 12 double-bend achromatic cells. Ten
      of 12 dispersion-free long straight sections are 5 m long and will be used for
      insertion devices and some accelerator components. The remaining two are each 15
      m long and reserved for advanced devices, such as a very long undulator or a free
      electron laser. A stretcher-booster ring, which is now under commission, will be
      used as an injector. In total, about 50 beamlines can be constructed and ten of
      them will be those of insertion devices. The present status of the project is
      'waiting for approval'.

PMID- 15263504
TI  - Isochronous storage ring of the New SUBARU project.
AB  - The aims of the New SUBARU project are to promote industrial applications in the
      VUV and soft X-ray region and to develop research and development towards new
      light sources. The main facility of the New SUBARU project is the 1.5 GeV
      electron storage ring which is under construction at the SPring-8 site in Harima
      Science Garden City, Japan. The storage ring is quasi-isochronous and has
      variable momentum dispersion for the deep study of beam dynamics in very short
      bunches.

PMID- 15263505
TI  - Compact synchrotron light source of the HSRC.
AB  - A 700 MeV synchrotron radiation source optimized in order to be incorporated in
      the university laboratory is under commissioning at Hiroshima University. The
      storage ring is of a racetrack type with two long straight sections for
      installing undulators. The bending field is as strong as 2.7 T, produced by
      normal-conducting magnet technology, and delivers synchrotron radiation with a
      critical wavelength of 1.42 nm. The strong magnetic field also enables a low
      energy injection scheme to be employed owing to the fast radiation damping. A 150
      MeV microtron has been adopted as the injector.

PMID- 15263506
TI  - Magnet lattice for the Siam Photon Source.
AB  - The magnet lattice for the Siam Photon Source, the first storage ring for
      synchrotron radiation research in Thailand, has been designed. The storage ring
      has a double-bend achromat lattice and fourfold symmetry with four straight
      sections. Although the magnet lattice is relaxed, an emittance value of 72 pi nm
      rad has been obtained, which is only 1.4 times as large as the theoretical
      minimum emittance with eight bending magnets. The dynamic aperture is found to be
      much larger than the physical aperture.

PMID- 15263507
TI  - Operational performance of the NIJI-III superconducting storage ring.
AB  - The operational performance of the NIJI-III superconducting storage ring has been
      studied with particular attention focused on the vacuum performance of the cold
      bore chamber. Photon-stimulated gas desorption in the cold-bore chamber was
      examined after commissioning the storage ring. It was confirmed that the photon
      stimulated gas desorption due to diffuse reflection of synchrotron radiation at
      the absorber was not dominant in the gas desorption when the electron beam was
      accumulated in the storage ring.

PMID- 15263508
TI  - Design study of a free-electron laser on a storage ring at Tohoku University.
AB  - A free-electron laser (FEL) based on the proposed Tohoku Light Source storage
      ring is discussed. In the first stage the FEL is made to operate in the visible
      region with a relative low beam energy to avoid the complication of mirrors.
      Then, with a higher beam energy, the FEL can produce radiation of wavelengths in
      the UV or VUV region. Some simulation results of the storage-ring FEL with
      wavelengths of approximately 200 nm are presented.

PMID- 15263509
TI  - Beam commissioning of the SPring-8 synchrotron.
AB  - The beam commissioning of the SPring-8 synchrotron was started in December 1996.
      In the first ten days, the coarse tuning of the pulse magnets for beam injection
      from the linac, and the excitation pattern of the dipole and the quadrupole
      magnets, were accomplished during energy ramping of the beam. The acceleration of
      the beam up to 8 GeV proceeded smoothly. From January to February 1997, the fine
      tuning of the synchrotron was continued and the operating parameters of all of
      the synchrotron equipment were decided.

PMID- 15263511
TI  - Suppressing the X-Y coupling effect in compact electron storage rings.
AB  - The x-y coupling effect, especially the tilt of the beam profiles, in the Super
      ALIS compact electron storage ring has been effectively eliminated. The main
      feature of this method is the suppression of the most harmful Fourier components
      of the skew-quadrupole perturbation by using just one thin skew-quadrupole
      magnet. Therefore, the method should be simple and effective for coupling
      suppression in compact storage rings that have little space for correction
      instruments.

PMID- 15263510
TI  - Proposal of a high-field superconducting wiggler for a slow positron source at
      SPring-8.
AB  - A low-energy positron beam is a unique probe of materials. In high-energy
      electron and positron storage rings it is possible to generate intense
      synchrotron radiation with a photon energy of 1-3 MeV by installing a high-field
      (8-10 T) superconducting wiggler. High-energy photons are converted to low-energy
      positrons by using a suitable target-moderator system. For an 8 GeV electron
      storage ring at a beam current of 100 mA, final yields are estimated to be about
      10(8)-10(10) slow-e(+) s(-1) or larger depending on the moderation efficiency,
      with the size of the positron source 10(1)-10(2) cm(2). In the present work a
      wiggler magnetic system of 10 T is proposed. The main parameters of the
      superconducting wiggler are presented.

PMID- 15263512
TI  - Reconstruction for the brilliance-upgrading project of the Photon Factory storage
      ring.
AB  - Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in
      progress to provide very brilliant synchrotron radiation to users, i.e. the
      emittance is being reduced by a factor of five. Components, such as the
      quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position
      monitors, are being replaced by new ones in 16 normal-cell sections of the PF
      ring. The accelerating cavities, injection systems and control systems are also
      being replaced. Operation will commence when the improvements are completed on 1
      October 1997.

PMID- 15263514
TI  - Effect of the RF cavity temperature on low-energy injection at HLS.
AB  - The resonant frequency shift caused by the temperature of the RF cavity at the
      Hefei Light Source has been measured and the results analysed. The effect of this
      frequency shift on low-energy injection with a low cavity voltage is discussed,
      and a new injection mode is proposed.

PMID- 15263513
TI  - Installation of new damped cavities at the Photon Factory storage ring.
AB  - New damped cavities have been installed in the Photon Factory (PF) storage ring
      and successfully operated in the last scheduled user run of 1996. The new damped
      cavity is a simple single-cell cavity with somewhat large beam-duct holes. The
      part of the beam duct that is attached to the cavity is made of SiC, which works
      as a microwave absorber and damps the higher-order modes excited in the cavity.
      Because of its simple structure, the operation of the cavity is very stable and
      also a high power input of more than 150 kW is possible. No coupled-bunch
      instabilities due to the new cavity were observed during operation.

PMID- 15263515
TI  - A crowbarless power supply for klystrons.
AB  - A new crowbarless power supply is to be installed at the New SUBARU storage ring.
      A high-power switching inverter unit eliminates the need for expensive and
      unstable crowbar circuits for the klystron power supply. It also realizes a very
      small voltage ripple in the low-frequency region. This is an important
      characteristic, especially in a quasi-isochronous storage ring such as New
      SUBARU.

PMID- 15263516
TI  - Submicrometre resolution phase-contrast radiography with the beam from an X-ray
      waveguide.
AB  - Experimental data with unprecedented submicrometre resolution obtained in a phase
      contrast radiography experiment in a magnifying configuration are presented. The
      term 'phase contrast' here indicates that the phase retardation of coherent light
      in matter was utilized as the contrast mechanism. The coherent and divergent beam
      exiting an X-ray waveguide was used in a lensless configuration to magnify
      spatial variations in optical path length up to several hundred times. The
      defocused image of a nylon fibre was measured with a resolution of 0.14 micro m
      at the object. Sufficient contrast was found for exposure times of 0.1 s, i.e. in
      the regime for real-time studies.

PMID- 15263517
TI  - RF system of the SPring-8 storage ring.
AB  - Construction of three RF stations in the storage ring of SPring-8 has been
      completed. The design concept concentrates on avoiding a coupled-bunch
      instability which limits the stored current or makes the synchrotron radiation
      beam unstable. The cavity is bell-shaped to reduce the coupling impedance of the
      higher-order modes. The cavity dimensions are trimmed systematically to
      distribute the higher-order mode frequencies. Each cavity has two movable tuners.
      The temperature of the cavity cooling water is controlled within 0.02 K and the
      water flow is kept constant. The construction and commissioning of the SPring-8
      storage ring RF system is reported.

PMID- 15263518
TI  - Magnetic measurement system for high-field magnets.
AB  - One of the main principles in electrodynamics, the change of magnetic field flux
      inducing an EMF in a wire coil, is applied for magnetic measurement. A scheme and
      the main parameters of the magnetic measurement system are described. The system
      was successfully used for magnetic measurement of a 7 T superconducting wiggler
      for LSU CAMD; results are presented.

PMID- 15263519
TI  - Construction of 714 MHz HOM-free accelerating cavities.
AB  - A new 'higher-order-mode (HOM)-free' accelerating cavity has been developed which
      can provide an accelerating voltage of more than 400 kV per cavity at a frequency
      of 714 MHz. The harmful HOMs in the cavities, which can induce beam instabilities
      at high beam currents, were heavily damped by using four special waveguide ports
      and broadband microwave loads. Two cavities of this design were installed in the
      1.54 GeV accelerator test facility (ATF) damping ring at KEK, and successfully
      stored beams. This cavity will also be very useful for synchrotron light sources.
      The basic design, characteristics of HOMs and construction of this cavity are
      reported.

PMID- 15263520
TI  - New method of Helmholtz coil alignment.
AB  - A new alignment method for Helmholtz coils is proposed. This method is based on a
      probe, whose axis is the same as the alignment axis. This probe includes one
      magnetic sensor, whose position is slightly shifted from the probe axis, and
      which is set perpendicular to the axis. Using this probe, the tilt and shift of
      the magnetic centre of Helmholtz coils can be aligned to within an order of 0.1
      mrad and 0.1 mm, respectively. Moreover, by this method, effects of terrestrial
      magnetism and tilt of the magnetic sensor can be removed from the measurement.
      This alignment method is presented along with an estimate of the alignment
      accuracy of the SPring-8 linac injector.

PMID- 15263521
TI  - Measurement of the electron energy and energy spread at the electron storage ring
      BESSY I.
AB  - Knowledge of the electron energy with a small uncertainty is necessary for the
      Physikalisch-Technische Bundesanstalt (PTB) to operate the electron storage ring
      BESSY I, and the future BESSY II, as a primary radiation source standard of
      calculable synchrotron radiation. At BESSY I the electron energy can now be
      measured either by the long-established method of resonant spin depolarization or
      by the newly set up method of Compton backscattering (CBS) of laser photons
      (CO(2) laser, lambda = 10.6 micro m). Results obtained at different electron
      energies by these two independent methods are presented. They agree within a
      relative uncertainty of better than 10(-4). The advantages and disadvantages of
      these two complementary techniques are described and applications of CBS for the
      measurement of other storage-ring parameters, e.g. the electron energy spread,
      are given.

PMID- 15263522
TI  - Operational evaluation of ultrahigh-vacuum protection systems for intense-photon
      flux wiggler beamlines.
AB  - The ultrahigh-vacuum (UHV) protection system at the 2.5 GeV synchrotron radiation
      source (positron storage ring) at the Photon Factory allows the intense-photon
      flux wiggler beamlines to operate safely during synchrotron radiation experiments
      for a long time. There are six high-power wiggler/undulator beamlines that
      provide intense photon-flux beams to the experimental hall. In the case of a
      possible instantaneous vacuum failure at the experimental hall, the intense
      photon-flux radiation from the wiggler could cause a meltdown of the titanium
      alloy fast-closing valve. The authors have developed a UHV protection system.
      Upon a vacuum failure, the protection system can dump the positron beam by
      turning off the RF power in the four RF klystrons (150 kW maximum), and then
      initiate a blade closure of the fast-closing valve. In this paper, the
      operational performance of the vacuum protection system for the intense-photon
      flux wiggler beamlines is evaluated and discussed regarding the actual vacuum
      deterioration downstream of a beamline at the experimental hall.

PMID- 15263523
TI  - A dynamic local bump system for producing synchrotron radiation with an
      alternating elliptical polarization.
AB  - To facilitate high-sensitivity soft X-ray magnetic circular dichroism
      experiments, a dynamic local bump system has been developed at the SRRC storage
      ring. This system was devised to vary dynamically the vertical slope of the
      electron beam in a bending magnet, producing, in the electron orbit plane, soft X
      rays with an alternating elliptical polarization. The local bump was created by
      using two pairs of vertical correctors located on each side of the bending
      magnet. The bump strength coefficient was obtained both from calculated
      estimation and from measured beam-response matrices. Control electronics for
      proper bump strength settings were designed to incorporate the existing orbit
      corrector function. A corresponding graphic user interface was implemented so
      that the bump amplitude could be easily adjusted. The performance of this system
      is presented. Disturbance on the stored electron beam orbit was observed while
      flipping the corrector polarity during EPBM (elliptical polarization from bending
      magnets) operation. A local feedback loop, developed to eliminate such
      disturbance on other beamlines, is also described.

PMID- 15263524
TI  - Performance of a fixed-taper in-vacuum undulator at SPring-8.
AB  - With an in-vacuum undulator, the smallest gaps can be used to achieve high
      brilliance radiation within a small spectral width around the harmonics of the
      fundamental. However, some experiments require a scan over a much wider range of
      energy within timescales which are impossible to reach via gap tuning. For
      standard undulators a flat spectrum is usually obtained by using a variable
      tapered gap. Unfortunately, the mechanical design of the in-vacuum undulator used
      at SPring-8 is hardly compatible with the extra degree of freedom necessary to
      adjust the taper mechanically. New magnetic designs are investigated to overcome
      this problem; their performances are compared with the performances of a fixed
      taper in-vacuum undulator for a source of photons in the 5-15 keV range (energy
      of the fundamental) with an energy width of 1.5 keV.

PMID- 15263525
TI  - In-vacuum undulators of SPring-8.
AB  - Most of the SPring-8 insertion devices are in-vacuum undulators except for the
      soft X-ray devices and one elliptical wiggler. The standard-type SPring-8 in
      vacuum undulator has a period of 32 mm and a minimum gap of 8 mm. The fundamental
      radiation energy ranges from 5.2 to 18.5 keV. Three standard in-vacuum undulators
      are already installed in the ring and are operating without any problems. The
      magnetic field correction, the vacuum system and the commissioning of the in
      vacuum undulators are described in this paper.

PMID- 15263526
TI  - SPring-8 in-vacuum undulator beam test at the ESRF.
AB  - Before the commissioning of SPring-8, the in-vacuum hybrid undulator developed at
      SPring-8 had been brought to the ESRF for the first beam test in the summer of
      1996. The purpose of this test was to investigate the influence of the in-vacuum
      undulator on the beam and check its vacuum system. However, heating by the
      resistive wall impedance turned out to be a critical issue for the in-vacuum
      undulators.

PMID- 15263527
TI  - Development of an in-vacuum minipole undulator.
AB  - An in-vacuum minipole (short-period) insertion device has been developed in a
      collaboration between SPring-8 and the National Synchrotron Light Source (NSLS).
      The magnetic arrays were constructed by SPring-8 and were installed in a chamber
      with mechanical parts in the X-ray ring (E = 2.584 GeV) at the NSLS in May 1997.
      The device is made of permanent magnets with 30.5 periods and a period length of
      11 mm. It is designed to produce fundamental radiation at 4.6 keV, and, with a
      modest value of deflection parameter (K = 0.7 at 3.3 mm gap), enables higher
      harmonics to be used for a variety of experiments.

PMID- 15263528
TI  - In-vacuum figure-8 undulator for hard X-rays with both horizontal and vertical
      polarization.
AB  - A figure-8 undulator of the in-vacuum type has been adopted as an insertion
      device for BL24XU, the Hyogo Beamline at SPring-8, to provide hard X-rays with
      both horizontal and vertical polarization instead of a tandem undulator
      consisting of horizontal and vertical undulators. The undulator will be operated
      with the gap almost fixed at 11.6 mm to provide the fundamental radiation with
      horizontal polarization at 9.5 keV and the 1.5th harmonic with vertical
      polarization at 14 keV.

PMID- 15263529
TI  - Construction of a vertical undulator at SPring-8.
AB  - A new-type insertion device (ID) has been constructed for the structural-biology
      beamline (BL45XU) at SPring-8. The ID consists of two undulators which can
      provide vertical polarized radiation (vertical undulators). By changing the
      individual gap of each undulator independently, photons with two different
      energies can be obtained. Magnetic field measurements show that the maximum
      horizontal field is 0.49 T and the magnetic performance is as good as expected.

PMID- 15263530
TI  - Initial results from an in-vacuum undulator in the NSLS X-ray ring.
AB  - A short-period in-vacuum undulator for the NSLS X-ray Ring has been developed in
      a collaboration between SPring-8 and the NSLS, and has achieved its project
      design goals during commissioning studies. The device is called IVUN (in-vacuum
      undulator) and employs magnet arrays (31 periods, with an 11 mm period) developed
      at SPring-8, while the requisite vacuum chamber and mechanical systems were
      developed at the NSLS. At a magnet gap of 3.3 mm, IVUN produces 4.6 keV radiation
      in the fundamental, with useful photon fluxes in both the second and third
      harmonics. The magnet gap is adjustable between 2 and 10 mm. A brief overview of
      IVUN is presented, together with initial commissioning results: the dependence of
      electron-beam lifetime and bremsstrahlung on magnet gap, and the output radiation
      spectrum.

PMID- 15263531
TI  - An SRRC elliptically polarizing undulator prototype to examine mechanical design
      feasibility and magnetic field performance.
AB  - In this work, a 1 m long Sasaki-type elliptically polarizing undulator (EPU)
      prototype with 5.6 cm period length is used to examine the mechanical design
      feasibility as well as magnetic field performance. The magnetic field
      characteristics of the EPU5.6 prototype at various phase shifts and gap motion
      are described. The field errors from mechanical tolerances, magnet block errors,
      end field effects and phase/gap motion effects are analysed. The procedures
      related to correcting the field with the block position tuning, iron shimming and
      the trim blocks at both ends are outlined.

PMID- 15263532
TI  - Spectral properties of the polarizing devices at SRRC.
AB  - User requirements at SRRC for high-brilliance synchrotron light in various
      polarization states will be fulfilled in the near future by the implementation of
      two types of polarizing devices in the storage ring: the elliptically polarizing
      undulator (EPU) and the elliptically polarized bending magnet (EPBM). The EPBM
      provides a broadband polarized spectrum up to the soft X-ray range with rapid
      alternation of the left and right helicities. The EPU, which has a magnetic
      period length of 56 mm, generates a high-brilliance harmonic spectral intensity
      in the range 80-1400 eV with abundant polarization states, including circular
      ones. The optimal merit flux is evaluated for the operation of these two
      polarizing devices in the SRRC 1.5 GeV storage ring. The available polarization
      states are also surveyed.

PMID- 15263533
TI  - SPring-8 twin helical undulator.
AB  - There are several ways of producing circularly polarized light, such as using
      asymmetric devices, crossed undulators etc. The SPring-8 helical undulator
      introduces a simple way of producing both horizontal and vertical fields in one
      undulator. All the magnet arrays are arranged above and below the plane of the
      electron orbit, so there is no limitation of access from the sides of the
      undulator. For the SPring-8 BL25SU, two helical undulators will be installed in
      tandem, and the helicity of the polarization can be switched at up to 10 Hz using
      five kicker magnets.

PMID- 15263534
TI  - OPHELIE: a variable-polarization electromagnetic undulator optimized for a VUV
      beamline at Super-ACO.
AB  - A planar/helical crossed overlapped undulator, called OPHELIE, is presented,
      composed of two identical ten-period (each 25 cm long) crossed undulators whose
      magnetic fields are produced by electromagnets. Such a design is quite simple,
      with only one mechanical translational motion, and versatile. After the
      presentation of the general concept of the crossed undulator and of its actual
      magnetic design, the expected performances in terms of flux and polarization
      capabilities are described. It appears that any state of polarization can be
      produced, at least on the first harmonic, with a large total polarization rate
      and a potentially high polarization switching frequency.

PMID- 15263535
TI  - Development of an elliptical multipole wiggler at SPring-8.
AB  - An elliptical multipole wiggler (EMPW) based on a new concept has been installed
      on the SPring-8 storage ring. The EMPW, with a 120 mm period, has a critical
      energy of 50 keV at a gap of 20 mm. It will provide high-brilliance hard
      circularly polarized X-rays in the 100-300 keV range to the pilot beamline
      dedicated to materials science: the Compton scattering beamline. Field
      measurements, field integrals, the expected fluxes, polarization rates, power and
      power densities are presented for two operating gaps: 30 mm during commissioning,
      20 mm later.

PMID- 15263536
TI  - Design of a 2 T multipole wiggler insertion device for the SRS.
AB  - Two new identical insertion devices have been designed for the Daresbury SRS.
      They are 2 T permanent-magnet multipole wigglers that will provide high flux in
      the X-ray region. This paper describes the magnetic and mechanical design of the
      arrays of steel pole pieces and permanent-magnet blocks. Also given is the
      engineering design of the support structure that will cope with the very large
      forces present while maintaining high levels of precision in gap setting and
      parallelism. The engineering design has been fully assessed using finite-element
      techniques to predict the deflections of critical parts of the structure. These
      two devices are due to be installed into the SRS by the end of 1998.

PMID- 15263537
TI  - The operation of a superconducting wiggler at TERAS.
AB  - A superconducting wiggler has been successfully installed at the ETL 800 MeV
      electron storage ring facility (TERAS). The operation of the wiggler at magnetic
      field strengths of 5 T with electron beam energy of 750 MeV has been
      accomplished. The wiggler has been designed and constructed to produce
      synchrotron radiation with critical photon energy around 3 keV for scientific,
      industrial and medical applications. We report here experiments that demonstrate
      the possibility of stable operation of a superconducting wiggler in a small
      storage ring.

PMID- 15263538
TI  - Superconducting 7 T wiggler for LSU CAMD.
AB  - A superconducting 7 T wiggler is under fabrication in a collaboration between
      Budker INP and LSU CAMD. The wiggler magnet has been successfully tested inside a
      bath cryostat and a maximum field of 7.2 T was achieved after six quenches. The
      main parameters of the wiggler and the method of the wiggler installation onto
      the storage ring are discussed.

PMID- 15263539
TI  - Insertion devices for BESSY II.
AB  - The high-brilliance synchrotron radiation source BESSY II will provide space for
      the installation of 14 insertion devices. At the time of writing (July 1997),
      eight insertion devices are funded. The first light for use by scientists will be
      available in January 1999. The undulators are designed for a scanning operation
      in parallel with the monochromator. This modus requires tight tolerances
      concerning the drive system. The first insertion device to be installed, a U-49
      undulator, has been assembled and magnetically measured. The r.m.s. phase error
      is 2 degrees. An endpole configuration using coils with less than 64 amp-turns
      makes the angular kick smaller than +/-3 micro rad over a gap range 15-50 mm.

PMID- 15263540
TI  - Undulators at HiSOR - a compact racetrack-type ring.
AB  - A compact racetrack-type 700 MeV storage ring (HiSOR) has been constructed at
      Hiroshima Synchrotron Radiation Center (HSRC). As the ring was planned for
      synchrotron radiation research on science and technology using VUV to X-rays up
      to 5 keV with limited size and cost, the ring was designed (i) to realize a high
      magnetic field (2.7 T) using conventional dipole magnets for higher critical
      energy, and (ii) to include two straight sections for insertion devices. A linear
      undulator (25-300 eV) and a new-type helical/linear undulator were installed at
      the two straight sections. The latter undulator consists of upper and lower jaws,
      as in a planar undulator; each jaw consists of one fixed magnet array at the
      centre and two magnet arrays on both sides. By longitudinal displacement of the
      side magnet arrays, the phase between the vertical and horizontal magnetic
      fields, and therefore the polarization (right- or left-circular, elliptical,
      linear) can be selected. The helical/linear undulator gives almost perfect
      circular polarization at 4-40 eV in the helical configuration without changing
      the phase of the magnet arrays, as well as linearly polarized light at 3-300 eV
      in the linear configuration.

PMID- 15263541
TI  - A superconductive undulator with a period length of 3.8 mm.
AB  - During recent years several attempts have been undertaken to decrease the period
      length of undulators to the millimetre range. In this paper a novel type of in
      vacuum undulator is described which is built using superconductive wires. The
      period length of this special device is 3.8 mm. In principle, it is possible to
      decrease this period length even further. A 100-period-long undulator has been
      built and will be tested with a beam in the near future.

PMID- 15263542
TI  - The PTB electromagnetic undulator for BESSY II.
AB  - The Physikalisch-Technische Bundesanstalt (PTB) will operate an electromagnetic
      undulator designed for radiometry at the BESSY II storage ring. The undulator has
      a period length of 180 mm, 21 full periods and a maximum magnetic induction of
      0.46 T, resulting in a tuning range of the first harmonic from 5 to 150 eV at 1.7
      GeV electron energy. Moreover, the electromagnetic design allows the undulator to
      be operated in a special mode with the period length doubled to 360 mm, thus
      accordingly shifting the tuning range to lower energies. The main design
      parameters of the undulator for radiometric applications, as well as measured
      magnetic field data, are presented.

PMID- 15263543
TI  - Performance of a helical undulator of the UVSOR.
AB  - A helical undulator was installed in the 0.75 GeV storage ring of the UVSOR
      facility of the Institute for Molecular Science. The undulator was designed to
      produce the fundamental of the circularly polarized undulator radiation in the
      energy range 2-43 eV, and the higher harmonics with elliptical polarization in
      the energy range up to 300 eV. Recently, the first spectrum from the undulator
      was observed. The performance of the undulator and the obtained spectrum are
      reported.

PMID- 15263544
TI  - Measurement of the coherence of synchrotron radiation.
AB  - The first-order spatial (transverse) coherence of synchrotron radiation has been
      measured using a Young's interferometer at BL28A (a helical-undulator beamline)
      of the Photon Factory, KEK. The range of the photon energy is about 70-180 eV.
      The visibility of the fringe was found to depend largely on the electron
      emittance and the intrinsic photon emittance. In principle, it is possible to
      gain knowledge of the very small electron emittance, of the order of 10(-10) m
      rad, without disturbing the electron beam in the storage ring.

PMID- 15263545
TI  - An insertion device for the soft X-ray photochemistry beamline at SPring-8.
AB  - A figure-8 undulator is an insertion device (ID) proposed at SPring-8 to reduce
      the heat-load problems encountered with ordinary linear undulators. This device
      is useful when the K value is high in order to obtain low-energy photons as the
      fundamental of the undulator radiation. It has therefore been adopted as the ID
      for the soft X-ray photochemistry beamline (BL27SU) at SPring-8 because linearly
      polarized photons between 100 and 2000 eV are necessary for the experiments on
      this beamline. The figure-8 undulator for BL27SU is now under construction and,
      in the first phase of operation, is expected to cover the energy range down to
      500 eV. In the second and third phases, the lowest energy may be reduced to 170
      and 100 eV, respectively.

PMID- 15263546
TI  - A practically zero horizontal magnetic field in a planar undulator used in the
      Tristan Super Light Facility.
AB  - The Tristan Main Ring (MR) at KEK (High Energy Accelerator Research Organization)
      has been used as a third-generation synchrotron radiation ring with an undulator
      installed in the MR as a third-generation light source. The magnetic field
      irregularities of the undulator were examined precisely. Measurement of the
      magnetic field after synchrotron radiation experiments showed that the magnetic
      irregularities in both the horizontal and vertical directions are negligibly
      small. This result suggests that our previous estimates of emittance, made using
      the measured undulator spectrum, should correctly represent the properties of the
      electron beam in the MR.

PMID- 15263547
TI  - Design of a local bump feedback system for a variably polarizing undulator.
AB  - A local bump feedback system is under construction to correct the orbit
      distortion caused by the magnetic field errors of a double-array undulator used
      to generate linear and circular polarization of light for a soft X-ray beamline.
      The local bump orbit is created by steering coils several turns long and four
      sets of steering magnets. The kick angle of the long steering coils and the
      steering magnets is determined according to the motion of the undulator and by
      detecting the beam position.

PMID- 15263548
TI  - A magnet model for a hybrid undulator assembly.
AB  - A modelling method, in which a single magnet block is divided into several sub
      blocks, is described. It is assumed that each sub-block is polarized
      homogeneously. The sub-block polarizations are derived with a genetic algorithm,
      which analytically calculates the total magnet flux density values generated by
      all sub-blocks and fits it to the values measured at the corresponding points in
      the vicinity of the magnet. The sub-block modellings accomplished show notable
      improvement in predicting the magnet flux density within the undulator gap when
      compared with a model based on homogeneously polarized blocks. The sub-block
      model can also be used when discarding bad magnets from a set. Finally, the
      results show that the inhomogeneities in individual magnets are one of the major
      reasons for poor predictability of the undulator field in hybrid devices.

PMID- 15263549
TI  - Advanced field-measurement method with three orthogonal Hall probes for an
      elliptically polarizing undulator.
AB  - A three-orthogonal-Hall-probe assembly with an 'on the fly' mapping method has
      been developed to characterize an elliptically polarizing undulator (EPU). The
      underlying design concept is that it can measure the three real field components
      without any field correction under a reliable and synchronization measurement
      method. Therefore, the relative central position shift, orthogonal angle and the
      planar Hall effect error between the three Hall probes should be calibrated and
      readjusted. Experimental results demonstrate that this method can yield an r.m.s.
      reproducibility of 10 G cm for the three field components and 2 G for the peak
      field strength. Under precision conditions this system can completely measure the
      three on-axis field components within 2 min for a 4 m-long EPU.

PMID- 15263550
TI  - Rotating/Helmholtz coil system using a lock-in amplifier method.
AB  - Measurement of integrated magnetic induction is an important part of the
      construction of insertion devices. The so-called 'flipping coil system' is
      normally utilized to characterize the integrated multipole components of the
      device, a requirement which varies from one storage ring to another. A Helmholtz
      coil system is used to determine a magnetization vector of each magnet piece in
      the device. Both systems are designed to measure the integrated magnetic flux to
      deduce the necessary quantities using the known relationship. We have developed
      an unconventional system which has a continuously rotating mechanism that allows
      the use of a lock-in amplifier instead of an integrator or a voltmeter. Detailed
      descriptions of the equipment are given.

PMID- 15263551
TI  - Effects of magnets with non-unit magnetic permeability on an elliptically
      polarizing undulator.
AB  - This study employs the three-dimensional magnetostatic code TOSCA to assess
      numerically the effects of NdFeB magnets with non-unit magnetic permeability on
      an elliptically polarizing undulator. A reduction of a few percent of the on-axis
      magnetic field strength is predicted. In addition, a deviation of +/-100 G cm
      uncompensated dipole steering is predicted in a phase shift of 180 degrees for
      the elliptically polarizing undulator EPU5.6 (having a period length of 56 mm) at
      the minimum gap of 18 mm, which is related primarily to the configuration of the
      device end scheme. Results presented herein demonstrate that implementing an
      active compensation mechanism is a prerequisite for minimizing the orbit
      distortion during phase-shift adjustment, particularly for operating such a
      polarizing undulator in a third-generation machine having a median energy similar
      to that of the 1.5 GeV storage ring at SRRC.

PMID- 15263552
TI  - A three-dimensional magnetostatics computer code for insertion devices.
AB  - RADIA is a three-dimensional magnetostatics computer code optimized for the
      design of undulators and wigglers. It solves boundary magnetostatics problems
      with magnetized and current-carrying volumes using the boundary integral
      approach. The magnetized volumes can be arbitrary polyhedrons with non-linear
      (iron) or linear anisotropic (permanent magnet) characteristics. The current
      carrying elements can be straight or curved blocks with rectangular cross
      sections. Boundary conditions are simulated by the technique of mirroring.
      Analytical formulae used for the computation of the field produced by a
      magnetized volume of a polyhedron shape are detailed. The RADIA code is written
      in object-oriented C++ and interfaced to Mathematica [Mathematica is a registered
      trademark of Wolfram Research, Inc.]. The code outperforms currently available
      finite-element packages with respect to the CPU time of the solver and accuracy
      of the field integral estimations. An application of the code to the case of a
      wedge-pole undulator is presented.

PMID- 15263553
TI  - First results from the crystal structure analysis beamline at SPring-8.
AB  - Results from the first measurements at the crystal structure analysis beamline
      (BL02B1) at SPring-8 are presented. The capabilities of this beamline are also
      discussed.

PMID- 15263554
TI  - Generalized grazing-incidence-angle X-ray diffraction (G-GIXD) using image
      plates.
AB  - A new and more 'generalized' grazing-incidence-angle X-ray diffraction (G-GIXD)
      method which enables simultaneous measurements both of in- and out-of-plane
      diffraction images from surface and interface structures has been developed.
      While the method uses grazing-incidence-angle X-rays like synchrotron radiation
      as an incident beam in the same manner as in 'traditional' GIXD, two-dimensional
      (area) detectors like image plates and a spherical-type goniometer are used as
      the data-collection system. In this way, diffraction images both in the Seemann
      Bohlin (out-of-plane) and GIXD geometry (in-plane) can be measured simultaneously
      without scanning the detectors. The method can be applied not only to the
      analysis of the in-plane crystal structure of epitaxically grown thin films, but
      also to more general research topics like the structural analysis of
      polycrystalline mixed phases of thin surface and interface layers.

PMID- 15263555
TI  - A versatile X-ray diffraction station at LNLS (Brazil).
AB  - Versatility was a major consideration in the project to provide an X-ray
      diffraction station at LNLS. At least two techniques are possible at the station:
      powder diffraction and multiple single-crystal diffraction. A two-crystal
      monochromator based on monolithic elastic translators, developed at LNLS, with
      sagittal focusing by the second crystal, allows 10 mrad of a >/=2 keV
      monochromatic beam to be used on the diffractometer. The station is equipped with
      a fast scintillation detector, imaging plates, a high-energy-resolution pin-diode
      detector, an ionization chamber and a high-angular-resolution soller slit. The
      data collection and control hardware and software were also developed at LNLS.
      The theta-2theta goniometry for powder diffraction on this 1 m-diameter
      diffractometer is based on commercial rotation tables. The multiple single
      crystal goniometry is realized by an independent elastic axis driven by
      differential micrometers for both high- and low-resolution angular movements. At
      least four independent axes can be positioned as necessary on the diffractometer
      table. Powder diffractograms and double-crystal rocking curves collected with the
      synchrotron beam show the expected quality.

PMID- 15263556
TI  - Protein crystallography using a multilayer monochromator.
AB  - A multilayer monochromator was installed on a bending-magnet beamline at the
      Cornell High Energy Synchrotron Source (CHESS) and was used to provide an
      unfocused pseudo-monochromatic X-ray beam for protein crystallography
      experiments. Datasets were collected from lysozyme at room temperature and human
      methylthioadenosine phosphorylase at 100 K. The wide energy bandpass of the
      multilayer allowed short exposure times, typically only a few times longer than
      on a focused multipole wiggler beamline. The diffraction images were processed
      using unmodified monochromatic data-processing software to yield datasets of good
      quality. These first measurements demonstrate that multilayer monochromators can
      be readily applied to the rapid structure determination of many typical-sized
      macromolecules.

PMID- 15263557
TI  - Beamline 14: a new multipole wiggler beamline for protein crystallography on the
      SRS.
AB  - A new multipole wiggler device has been designed for the 2.0 GeV Synchrotron
      Radiation Source at Daresbury Laboratory in the UK. The nine-pole 2.0 T device
      will provide radiation for two beamlines dedicated to protein crystallography,
      one of which will be of high intensity. This article provides details of the
      design of the two stations and outlines methods being developed to combine
      dealing with the high heat load from the radiation while allowing both stations
      to be built as close to the centre of the fan as possible.

PMID- 15263558
TI  - Focusing monochromator and imaging-plate camera for grazing-incidence diffraction
      studies of thin films.
AB  - A multiple-imaging-plate detector system and focusing monochromator have been
      developed and successfully applied to the time-resolved study of phase
      transitions in Langmuir-Blodgett films by grazing-incidence X-ray diffraction
      (GIXD). The monochromator described here combines fixed-exit-beam height with
      sagittal focusing of the second crystal. The design is similar to that of
      Matsushita et al. [Matsushita, Ishikawa & Oyanagi (1986). Nucl. Instrum. Methods,
      A246, 377-379], with the exception that the motion of the first crystal is
      achieved via a computer-controlled X-Y translation table rather than a set of
      cams. The second crystal is a ribbed Si(111) wafer mounted in a four-point
      bending mechanism. The first reported application of imaging plates to a GIXD
      study was carried out by our group and proved to be very successful in the
      determination of thin-film structure [Foran, Peng, Steitz, Barnes & Gentle
      (1996). Langmuir, 12, 774-777]. To extend the capabilities of this system, an
      imaging-plate camera was designed and built which can accommodate up to 13
      imaging plates (40 x 20 cm) inside the vacuum chamber of the main diffractometer
      at the Australian Beamline at the Photon Factory.

PMID- 15263559
TI  - Improvement of beamline 4B9A and results of an X-ray diffraction experiment.
AB  - 4B9A is a focusing and monochromatic photon beam at the BSRF, which was
      constructed in 1990. During the second phase of the BSRF program, the surface of
      the cylindrical mirror has been coated with Pt, covering the original Ni, and the
      monochromator has been upgraded. The maximum photon energy extends to 11 keV and
      the intensity has increased about tenfold with respect to the previous intensity
      at 6 keV. Synchrotron X-ray diffraction patterns for the Hg-1223
      (HgBa(2)Ca(2)Cu(3)O(8+delta)) superconducting bulk and thin film have been
      measured at 1.54014 A. Results indicate that the bulk and film can be indexed as
      possessing tetragonal symmetry; lattice parameters a = 3.856 A and c = 15.851 A
      for the bulk Hg-1223 compound, and a = 3.8517 A and c = 15.8511 A for the film.
      Their structures are similar.

PMID- 15263560
TI  - First performance assessment of the small-angle X-ray scattering beamline at
      ELETTRA.
AB  - The double-focusing high-flux wiggler beamline dedicated to small-angle X-ray
      scattering (SAXS) and wide-angle X-ray scattering (WAXS) at ELETTRA has gone into
      user operation recently. It has been designed specifically for time-resolved
      studies of non-crystalline and fibrous materials in the submillisecond time
      scale, and has been optimized for small-angle scattering measurements. An
      overview of the beamline status and of some representative results, highlighting
      the performance of the SAXS beamline, are given.

PMID- 15263561
TI  - Material analysis end-station of the Hyogo-ken beamline at SPring-8.
AB  - Plans to construct surface-analysis equipment which will be placed on beamline
      BL24XU of SPring-8 are presented. There are three experimental hutches in BL24XU,
      which are available simultaneously by using diamond monochromators as beam
      splitters. The purpose of the surface-analysis equipment is the simultaneous
      measurement of fluorescent and diffracted X-rays in grazing-incidence geometry.
      The instrument is equipped with a solid-state detector (SSD) and a flat position
      sensitive proportional counter (PSPC) combined with analysing crystals for X-ray
      fluorescence (XRF) analysis. A curved PSPC and the goniometer that mounts the SSD
      used for XRF are also installed for X-ray diffraction. X-ray fluorescence
      holography and polarized X-ray emission spectroscopy modes are available, so
      three-dimensional images of atomic configurations and also the anisotropic
      structure of materials will be studied.

PMID- 15263562
TI  - The commissioning of a flexible low-cost multipurpose X-ray beamline at SRRC.
AB  - A low-cost multipurpose X-ray beamline has been commissioned at the bending
      magnet B15 of the Synchrotron Radiation Research Center (SRRC). The beamline is
      constructed in such a way to accommodate the various needs of small research
      consortia, from universities or research institutes, whose requirements of a
      beamline facility are quite diverse while under limited funding support.
      Flexibility is the special feature of this beamline. It is capable of performing
      quick test measurements without a prolonged reviewing process. Switching between
      different techniques, such as white-beam irradiation, EXAFS and X-ray scattering,
      can be achieved within 1 h. Novel experiments, such as energy-dispersive small
      angle scattering experiments and energy-dispersive reflectivity measurements, can
      also be performed.

PMID- 15263563
TI  - Cryogenic high-resolution X-ray spectrometers for SR-XRF and microanalysis.
AB  - Experimental results are presented obtained with a cryogenically cooled high
      resolution X-ray spectrometer based on a 141 x 141 micro m Nb-Al-Al(2)O(3)-Al-Nb
      superconducting tunnel junction (STJ) detector in an SR-XRF demonstration
      experiment. STJ detectors can operate at count rates approaching those of
      semiconductor detectors while still providing a significantly better energy
      resolution for soft X-rays. By measuring fluorescence X-rays from samples
      containing transition metals and low-Z elements, an FWHM energy resolution of 6
      15 eV for X-rays in the energy range 180-1100 eV has been obtained. The results
      show that, in the near future, STJ detectors may prove very useful in XRF and
      microanalysis applications.

PMID- 15263564
TI  - The Dutch-Belgian beamline at the ESRF.
AB  - A brief description is given of the design principles and layout of the Dutch
      Belgian beamline at the ESRF. This beamline optimizes the use of the available
      bending-magnet radiation fan by splitting the beam into two branches, each
      accommodating two experimental techniques.

PMID- 15263565
TI  - Commissioning and first results of the LNLS XAFS beamline.
AB  - An X-ray absorption fine-structure spectroscopy beamline has been installed and
      commissioned at a bending-magnet source at LNLS. Three monochromators are
      available: a channel-cut, a double-crystal and a four-crystal set-up. They have
      been operated from 2500 up to 15000 eV, with a resolving power better than 5500
      in the full range. Photon flux of the order of 10(8) photons s(-1) up to 10(10)
      photons s(-1) has been attained. The experimental station is equipped with a
      table that can withstand a weight of 300 kg and track the vertical position of
      the beam with a 2.5 micro m accuracy over a 120 mm stroke. The beamline has been
      fully characterized and the first results are presented.

PMID- 15263566
TI  - Design and feasibility of quick EXAFS scans for a 'broomstick' double-crystal
      monochromator at PLS beamline.
AB  - A data-collection technique for quick extended X-ray absorption fine-structure
      spectroscopy (QEXAFS) was developed with a new 'broomstick' double-crystal
      monochromator, which has been installed for X-ray absorption fine-structure
      (XAFS) applications at the Pohang Light Source. The monochromator operates in a
      fixed-exit scan mode as the Bragg angle is varied from 8 to 80 degrees,
      corresponding to 2-14 keV, using an Si(111) crystal. The monochromator scan
      capability was investigated by analysing EXAFS data quality from step-scan and
      from continuous rotation of the Bragg crystal reflection angle. In our fast
      continuous-scan design, the electronic pulsing speed of the step motor is
      adjustable to avoid the monochromatic beam instability caused by serious
      mechanical resonance. The feasibility of QEXAFS scanning is demonstrated by a
      typical EXAFS scan (e.g. 1 keV range) being taken within 1 min.

PMID- 15263567
TI  - New beamline optics for the effective use of a wiggler beam.
AB  - A hard X-ray beamline, BL13A, has been constructed for precision diffraction
      experiments conducted downstream of the multipole wiggler MPW#13 at the Photon
      Factory. The BL13A line can be used along with the main beamline, BL13B, which
      accepts the central 4 mrad of the 5 mrad horizontal fan. BL13A uses the remaining
      horizontal off-axis beam. The beam is diffracted by a double-crystal
      monochromator which uses asymmetric (422) diffraction with a horizontal
      diffraction vector. A monochromatic beam with 33.5 keV photon energy is directed
      to a precision goniometer. Good beam stability and high intensity were obtained.

PMID- 15263568
TI  - New wiggler beamlines at BSRF.
AB  - A new multipole wiggler has been installed in the ring of the Beijing Electron
      Positron Collider (BEPC), and two new beamlines were extracted from it for
      experiments, including LIGA, microprobe fluorescence analysis, high-pressure
      diffraction and soft X-ray research. The beam profile and photon intensity were
      measured and compared with the calculated values. The main parameters and
      characteristics of the two beamlines are illustrated. Some experimental results
      are presented.

PMID- 15263569
TI  - X-ray absorption beamline at the Mitsubishi compact storage ring.
AB  - Beamline #5 (BL#5) at the Mitsubishi compact storage ring (MELCO-SR) is a
      beamline designed to perform X-ray absorption experiments in the 1-5 keV energy
      range. MELCO-SR is a racetrack-type storage ring with compact superconducting
      magnets, which is operated at 600 MeV, mainly for X-ray lithography experiments.
      As the ring is set in a shield wall of 2 m thickness, a point just outside the
      shield wall of BL#5 is located at 6.8 m from the source point. A small toroidal
      mirror, located inside the shield wall at 3.4 m from the source, focuses the beam
      vertically and horizontally onto the 7.3 m point. This simple optical
      configuration allows us to bring the source point outside of the shield wall, and
      to collect about 10 mrad horizontally and maintain small footprints on the
      monochromator crystal. A new 'Cowan type' monochromator, located at 7.4 m from
      the source and selected for simplicity of design and for stability, will provide
      a bright high-resolution and stable X-ray beam for use in the X-ray spectroscopy
      of electronic materials in MELCO.

PMID- 15263570
TI  - Construction of the JAERI soft X-ray beamline for actinide material sciences.
AB  - An undulator beamline for spectroscopy studies focusing on the electronic
      structure of actinide materials is under construction. Linearly or circularly
      polarized soft X-rays are provided by employing a variably polarizing undulator.
      Varied-line-spacing plane gratings and a sagittal-focusing system are used to
      monochromatize the undulator beam, whose energy ranges from 0.3 to 1.5 keV. A
      resolving power of 10(4) is expected in the whole energy region. These components
      are methodically operated by the SPring-8 beamline control system. There are
      three experimental stations in the beamline. In one of the stations the
      photoemission spectroscopy experiments are carried out at a radioisotope
      controlled area where actinide compounds as well as unsealed radioactive
      materials are usable. Other experimental stations are planned in the beamline for
      surface photochemical reactions and biological applications.

PMID- 15263571
TI  - The LNLS soft X-ray spectroscopy beamline.
AB  - The soft X-ray spectroscopy beamline installed at a bending-magnet source at the
      LNLS is described. The optics are designed to cover energies from 800 to 4000 eV
      with good efficiency. The focusing element is a gold-coated toroidal mirror with
      an angle of incidence of 17 mrad. The UHV double-crystal monochromator has three
      pairs of crystals, Si (111), InSb (111) and beryl (101;0), that can be selected
      by a sliding movement. The UHV workstation is equipped with an ion gun, an
      electron gun, an electron analyser, LEED optics, an open channeltron and a
      photodiode array. This beamline is intended for photoemission, photoabsorption,
      reflectivity and dichroism experiments.

PMID- 15263572
TI  - Twin helical undulator beamline for soft X-ray spectroscopy at SPring-8.
AB  - A very high resolution soft X-ray beamline, BL25SU, has been designed and is
      under construction at SPring-8. Completely right or left circularly polarized
      light is supplied on a common axis of a newly designed twin helical undulator. A
      helicity modulation up to 10 Hz can be performed using five kicker magnets. The
      fundamental radiation covers the region 0.5-3 keV. Higher-order radiation is
      rather weak on the axis. A monochromator with varied-line-spacing plane gratings
      is installed to cover the region below 1.5 keV. A very high resolution beyond
      10(4) is expected for the whole energy region.

PMID- 15263574
TI  - A beamline for photochemical processes at atmospheric pressure.
AB  - A beamline especially designed for atmospheric photochemical reactions has been
      constructed at the NTT synchrotron radiation facility. By inserting a buffer
      helium chamber with Be and Si(3)N(4) partition windows between the beamline and
      the reaction chamber, studies can be performed without the differential pumping
      systems normally used in existing photochemistry beamlines. The reaction chamber
      is equipped with a gas supply system and analysis systems to investigate gas
      phase and surface reactions. Purging using dry purified gases in combination with
      water-bubbling gives effective control of water concentration in the reaction
      chamber.

PMID- 15263573
TI  - Soft X-ray photochemistry beamline at SPring-8.
AB  - Design and construction of a soft X-ray beamline at SPring-8 is reported. The
      beamline utilizes high-quality linearly polarized soft X-rays obtainable from a
      figure-8 undulator for the study of photophysical and photochemical processes of
      atoms, molecules and surfaces in the inner-shell excitation region. It consists
      of two experimental stations, a photochemistry station and a chemical vapour
      deposition (CVD) station. A high-resolution grating monochromator is installed at
      the photochemistry station, while the intense undispersed undulator radiation is
      used at the CVD station. Unique features of the experimental chambers and of the
      analysis and characterization systems are described along with those of the
      monochromator.

PMID- 15263575
TI  - A high-performance wide-range beamline for elliptically polarized undulator
      source.
AB  - A high-performance wide-range beamline has been designed for monochromatizing
      circularly polarized photons with energies from 10 to 1400 eV. A grazing SGM
      based beamline with two entrance slits has been employed to optimize the
      performance. The degree of the circular polarization affected by the beamline
      optics has been analysed. The horizontal and vertical refocusing mirrors have
      been specially arranged to improve greatly the polarization degree in the low
      energy region. By connecting this beamline to a high-efficiency elliptically
      polarized undulator, this beamline should be able to provide, in the entire
      energy range, intensive and high-resolution photons of a high degree of circular
      polarization.

PMID- 15263576
TI  - A grazing-incidence reflectometer for BL-39XU at SPring-8.
AB  - A new grazing-incidence reflectometer has been designed for the X-ray undulator
      beamline BL-39XU at SPring-8. It will be used for analytical applications,
      especially ultra-trace-level determination by total reflection X-ray fluorescence
      (TXRF), nanometer-scale surface topography by specular/non-specular X-ray
      reflection, and thin-film interface studies by combined measurements of X-ray
      fluorescence and X-ray reflection. The requirements for the instrument and the
      solutions in the present design are discussed. A prototype has been developed to
      test the feasibility of the design. It has been confirmed that the measurements
      planned at the beamline are achievable with this reflectometer.

PMID- 15263577
TI  - A compact vacuum-ultraviolet beamline for synchrotron radiation photoelectron
      spectroscopy combined with an ion-scattering spectrometer, SORIS.
AB  - Apparatus for high-resolution synchrotron radiation photoelectron spectroscopy
      combined with high-resolution medium-energy ion scattering, named 'SORIS', has
      been developed for simultaneous investigations of electronic states and atomic
      structures on surfaces. For this purpose, a compact vacuum-ultraviolet beamline
      of photon energy from 5 to 700 eV has been designed for the small storage ring
      'Aurora' installed at Ritsumeikan University. Owing to the small electron-beam
      size in the storage ring, an energy resolution E/dE of >5000 can be obtained.

PMID- 15263578
TI  - Optical design of the NSRL undulator beamline.
AB  - The optical design of the NSRL undulator beamline is presented. The NSRL
      undulator has 29 periods of 9.2 cm that produce a photon energy of 7.7-124 eV
      with the fundamental and third harmonics at a ring energy of 800 MeV. The
      beamline consists of a typical Kirkpatrick-Baez prefocusing mirror system, a
      modified spherical-grating monochromator (SGM) and a refocusing toroidal mirror.
      The monochromator has two including angles of 148 and 157 degrees with two plane
      mirrors inserted into the entrance arm in order to cover the wide energy range
      with high grating diffraction efficiency. Calculation shows that the resolving
      power of the monochromator can be greater than 5000 with the slits fully opened
      and 20000 with a 20 micro m opening of the slits. The spot at the sample is about
      1.5 (H) mm x 0.5 (V) mm.

PMID- 15263579
TI  - Design of a high-flux and high-resolution VUV bending-magnet beamline.
AB  - A high-flux and high-resolution VUV beamline (4-40 eV) has been designed and is
      under construction at SRRC. This beamline, which collects 50 mrad of horizontal
      radiation, uses a 6 m cylindrical-grating monochromator with an incident angle of
      70 degrees instead of the conventional normal-incidence-monochromator (NIM)
      design. Special features, such as movable entrance slit, bendable vertical
      focusing mirror and movable curved exit slit, are employed to enhance greatly the
      beamline performance. With both slit openings set at 10 micro m, the energy
      resolving power can reach as high as 70000. Photon fluxes of 1 x 10(13) and 1 x
      10(10) photons s(-1) are calculated for energy-resolving powers of 1000 and
      40000, respectively. The best image size at the sample position is smaller than
      0.45 x 0.2 mm.

PMID- 15263581
TI  - Performance of the VUV beamline 4.1 at the SRS, Daresbury Laboratory.
AB  - The performance of a recently commissioned beamline, designated BL4.1, at the
      SRS, Daresbury Laboratory, is described. This beamline covers the energy range 15
      >/= hupsilon >/= 200 eV, using a spherical grating monochromator, and is equipped
      with a UHV surface-science endstation containing a Scienta SES200 and an HA54
      angle-resolving electron-energy analyser. Design parameters and optical
      specifications are tabulated. Monochromator resolution has been determined by
      measuring the Fermi edge of a Pt foil cooled to 40 K and these values are
      compared with the calculated resolution. The flux delivered to the endstation has
      been measured directly using a calibrated photodiode. The performance of the
      beamline is further illustrated by reference to a study of the angular
      distribution of photoemitted intensity from a band-gap state on a TiO(2)(110) 1 x
      2 surface.

PMID- 15263580
TI  - The gas-phase photoemission beamline at Elettra.
AB  - This paper reports the present stage of commissioning of the gas-phase
      photoemission beamline at Elettra, Trieste. The beamline is designed for atomic
      and molecular science experiments with high-resolution and high-flux synchrotron
      radiation. It consists of an undulator source, variable-angle spherical-grating
      monochromator and two experimental stations. The design value of the energy range
      is 20 to 800 eV with a specified resolving power of over 10000. The procedure
      adopted for calibration of this type of monochromator is discussed. At present a
      resolving power up to 20000 and a range up to 900 eV have been measured.
      Absorption spectra taken at the argon L(II,III)-edge and at the nitrogen, oxygen
      and neon K-edges are as sharp as, or sharper than, any reported in the
      literature. The instrumental broadening is well below the natural line-width
      making it difficult to quantify the resolution; this problem is discussed.

PMID- 15263582
TI  - Optical design for a bending-magnet beamline based on a varied-line-spacing plane
      grating.
AB  - A vacuum ultraviolet beamline with a grazing-incidence constant-deviation-angle
      monochromator, equipped with a varied-line-spacing plane grating, has been
      designed for a bending-magnet light source. This type of monochromator has become
      very popular because of its high resolution, high throughput, simple scanning
      mechanism and fixed exit slit. To improve the energy resolution for a wide
      spectral range, Yan & Yagishita [(1995), KEK Report 95-9. KEK, Tsukuba, Ibaraki
      305, Japan] proposed eliminating the defocus aberration at two specific energies
      in the spectral range, and their monochromator successfully achieved higher
      energy resolution by using an undulator light source. The possibility of applying
      this method to a bending-magnet beamline was examined and it was found that high
      performance can be achieved even using a bending-magnet light source with wide
      emittance. Performance evaluation relating to energy resolution, photon flux and
      spot size are reported.

PMID- 15263583
TI  - SINBAD, a brilliant IR source from the DAPhiNE storage ring.
AB  - SINBAD is the Italian IR synchrotron radiation beamline, designed to work at
      wavelengths greater than 10 micro m. It is being installed on DAPhiNE, a new
      collider that is designed to work at 0.51 GeV with a beam current up to 5 A. Due
      to such a high current, the IR extracted from a bending magnet will be more
      brilliant than that of a black body at 2000 K by two orders of magnitude at 100
      micro m. The beamline optical system, projected by ray-tracing simulation,
      consists of six mirrors that first focus the radiation on a wedged CVD diamond
      film window and then transfer the collimated beam to the experimental area where
      a Michelson interferometer will be installed.

PMID- 15263584
TI  - Upgraded IR beamline at UVSOR.
AB  - BL6A1, a far-infrared (FIR) beamline at UVSOR, originally built in 1986, has been
      recently upgraded. The upgrade included the introduction of a second FT-IR
      spectrometer, making it possible to cover the entire FIR-IR range (3-10000 cm(
      1)) in one sequence of measurements, without having to open the sample chamber;
      the beamline has become a more convenient and powerful experimental station than
      before. The upgrade is also expected to enable such experiments as IR studies of
      molecules adsorbed on solid surfaces, and time-resolved IR spectroscopies. This
      paper describes the characteristics of the upgraded BL6A1.

PMID- 15263585
TI  - Design of a pre-slit for SPring-8 undulator beamlines.
AB  - A volumetric heating method is applied to the pre-slit placed on the SPring-8
      standard-undulator beamline front ends in order to handle the very intensive
      photon beam. A graphite block is used as the radiation-absorbing body, which is
      brazed to a cooling holder made of oxygen-free high-conductivity copper. Various
      experiments and calculations have been carried out on the strength of the brazed
      joint. Comparisons between the experiments and calculations show that static
      fracture of the joint would not occur even under the highest heat load. The
      outgassing properties of the graphite blocks are also presented here.

PMID- 15263586
TI  - A new UHV angle encoder for high-resolution synchrotron radiation monochromators.
AB  - The high precision of 0.1 arcsec required for the positioning of optical elements
      in new two-axes monochromators at the undulator beamlines at BESSY II has led to
      the development of UHV-compatible high-precision angle encoders. Mounted directly
      on the rotation axes, they provide substantial advantages over measuring systems
      connected outside the vacuum vessel. Making use of a fast closed-loop control
      system, an accuracy of 0.1 arcsec at a resolution of less than 0.01 arcsec has
      been experimentally verified.

PMID- 15263587
TI  - A novel approach to the control of experimental environments: the ESCA microscopy
      data-acquisition system at ELETTRA.
AB  - An efficient control system is today one of the key points for the successful
      operation of a beamline at third-generation synchrotron radiation sources. The
      high cost of these ultra-bright light sources and the limited beam time requires
      effective instrument handling in order to reduce any waste of measurement time.
      The basic requirements for such control software are reliability, user
      friendliness, modularity, upgradability, as well as the capability of integrating
      a horde of different instruments, commercial tools and independent pre-existing
      systems in a possibly distributed environment. A novel approach has been adopted
      to implement the data-acquisition system of the ESCA microscopy beamline at
      ELETTRA. The system is based on YASB, a software bus, i.e. an underlying control
      model to coordinate information exchanges and networking software to implement
      that model. This 'middleware' allows the developer to model applications as a set
      of interacting agents, i.e. independent software machines. Agents can be
      implemented using different programming languages and be executed on
      heterogeneous operating environments, which promotes an effective collaboration
      between software engineers and experimental physicists.

PMID- 15263588
TI  - SPring-8 beamline control system.
AB  - The SPring-8 beamline control system is now taking part in the control of the
      insertion device (ID), front end, beam transportation channel and all interlock
      systems of the beamline: it will supply a highly standardized environment of
      apparatus control for collaborative researchers. In particular, ID operation is
      very important in a third-generation synchrotron light source facility. It is
      also very important to consider the security system because the ID is part of the
      storage ring and is therefore governed by the synchrotron ring control system.
      The progress of computer networking systems and the technology of security
      control require the development of a highly flexible control system. An interlock
      system that is independent of the control system has increased the reliability.
      For the beamline control system the so-called standard model concept has been
      adopted. VME-bus (VME) is used as the front-end control system and a UNIX
      workstation as the operator console. CPU boards of the VME-bus are RISC processor
      based board computers operated by a LynxOS-based HP-RT real-time operating
      system. The workstation and the VME are linked to each other by a network, and
      form the distributed system. The HP 9000/700 series with HP-UX and the HP
      9000/743rt series with HP-RT are used. All the controllable apparatus may be
      operated from any workstation.

PMID- 15263589
TI  - Object library for a new generation of experiment-controlling applications under
      the UNIX operating system.
AB  - The Interface Object Library based on the Motif extension of the X Windows system
      and on the ESONE SVIC-VCC Library is presented. Some features of the applications
      for controlling a synchrotron radiation experiment are discussed. The Interface
      Object Library is written in the object-oriented C++ language. The library class
      hierarchy structure is presented and discussed. Several interfaces were realized
      in the Interface Object Library: the Windows interface, the CAMAC interface and
      the interface for supporting the experiment. The behaviour of the objects
      describing the CAMAC crate and CAMAC block is discussed. The application of these
      protocols for controlling the fast one-coordinate position-sensitive X-ray
      detector OD3 is presented.

PMID- 15263590
TI  - Characterization of windows and filters for coherent X-ray beamlines.
AB  - Beryllium windows and graphite heat absorbers used in coherent X-ray beamlines
      must be optically flat. If the optical path through the window varies by more
      than lambda/4, the X-ray wave front will be distorted after passing through the
      window, and the divergence of the X-ray beam may be increased. This reduces the
      beam coherence. Beryllium, graphite and Kapton films have been tested using ultra
      small-angle X-ray scattering. Wave-front distortion was also directly observed by
      means of phase-contrast X-ray microradiography. The measured increase of angular
      divergence is about 4 micro rad. The wave-front distortion is larger than 2pi
      (optical path difference of lambda). These are serious problems for utilizing
      coherent X-ray beams.

PMID- 15263591
TI  - SCIPE - a simple control interface protocol for experimenters.
AB  - The simple control interface protocol for experimenters (SCIPE) used at Sector 5
      of the Advanced Photon Source is presented. This interface provides a generic
      method for data-acquisition programs to control generic actuators and detectors
      on a synchrotron beamline. The implementation used by the DuPont-Northwestern-Dow
      Collaborative Access Team, based on readily available hardware, is also
      described.

PMID- 15263592
TI  - New transmission-type X-ray filters consisting of amorphous multilayer films.
AB  - New transmission-type X-ray filters have been developed. The filters consist of X
      ray-amorphous metal (less than 30 A)/metalloid ( approximately 10 A) multilayer
      films sputter-deposited on X-ray-transparent polymer substrates. Such
      metal/metalloid multilayer films show only very broad diffraction peaks, since
      the metal and metalloid layers forming the multilayer films are usually X-ray
      amorphous if the layers are sufficiently thin. The filters use the wavelength
      dependent absorption phenomena near absorption edges of elements to reduce the
      intensity of transmitted X-rays, without generating any crystalline sharp peaks
      which cause serious problems in experiments such as fluorescence XAFS
      measurements. The multilayer-film filters were prepared by a multi-target
      magnetron sputtering deposition technique, paying special attention to the
      homogeneity of the layer thickness by spinning substrates of the films. The
      filters are useful in reducing the intensity of undesirable fluorescence
      emissions and improving the signal-to-background ratios of data acquired in
      various measurements using a solid-state detector.

PMID- 15263593
TI  - Front-end XY-slits assembly for the SPring-8 undulator beamlines.
AB  - A front-end XY-slits assembly has been designed for the SPring-8 undulator
      beamlines. This assembly can handle the high heat flux from the undulator, its
      grazing-incidence L-shaped configuration employing an enhanced heat-transfer
      technology.

PMID- 15263594
TI  - Allowable aperture size of the front end for the high-heat-load undulator
      beamlines of SPring-8.
AB  - A systematic study to determinine the allowable aperture size of the front end
      for the SPring-8 high-heat-load undulator beamlines has been performed, from the
      viewpoint of protecting the front-end Be window from thermomechanical failure,
      and based on the results of ANSYS finite-element analyses. These results have
      revealed that the allowable aperture size of the front end ranges approximately
      from 1.06 mm(2) to 3.2 mm(2) depending on the K-parameter and the filter
      thickness.

PMID- 15263595
TI  - Development of a three-electrode-lens drift tube for time-of-flight mass
      spectrometry.
AB  - A three-electrode-lens drift tube for time-of-flight mass spectrometry (TOF-MS)
      has been developed for utilizing a detector to observe photon-stimulated
      desorption (PSD). In spite of a small detection area, the detector has a high
      detection efficiency and durability to reactive gas atmosphere at high pressure.
      The TOF-MS performance of the drift tube was examined for PSD using single-bunch
      mode synchrotron radiation on a dichlorosilane (SiH(2)Cl(2))-saturated Si(001)
      surface. The measured acceleration and focusing-voltage dependences of the time
      of flight, intensity and full width at half-maximum for the peak of H(+) and
      Cl(+) PSD ions are discussed in terms of the numerical calculations of ion
      trajectories and focusing characteristic of the drift tube.

PMID- 15263596
TI  - Shielding design calculation for SPring-8 beamlines using STAC8.
AB  - The beamlines of SPring-8 are classified by synchrotron radiation source into
      undulator, wiggler and bending-magnet beamlines for safety analysis. The
      shielding design calculations for synchrotron radiation are performed with a new
      shielding design code, STAC8, taking into consideration the linear-polarization
      effect, the slant length of the shield hutch wall and the build-up effect as
      functions of scattering angle and azimuthal angle.

PMID- 15263597
TI  - Single-pass BPM system of the Photon Factory storage ring.
AB  - At the 2.5 GeV ring of the Photon Factory, a single-pass beam-position monitor
      (BPM) system is being prepared for the storage ring and the beam transport line.
      In the storage ring, the injected beam position during the first several turns
      can be measured with a single injection pulse. The BPM system has an adequate
      performance, useful for the commissioning of the new low-emittance lattice.
      Several stripline BPMs are being installed in the beam transport line. The
      continuous monitoring of the orbit in the beam transport line will be useful for
      the stabilization of the injection energy as well as the injection beam orbit.

PMID- 15263598
TI  - A synchrotron radiation beam-position monitor at the Taiwan Light Source.
AB  - A prototype photon-beam-position monitor has been designed, fabricated and tested
      at the Taiwan Light Source of the Synchrotron Radiation Research Center.
      Aluminium was chosen as the material of the blade electrodes due to its low
      atomic number and high thermal conductivity. The resolution of this photon-beam
      position monitor was <+/-1 micro m. The sensitivity of the blade electrode has
      been measured in situ. Results of measurements for bending-magnet light and
      undulator light with different gaps are described.

PMID- 15263599
TI  - New beam-position monitor system for upgraded Photon Factory storage ring.
AB  - Accompanying the brilliance-upgrading project at the Photon Factory storage ring,
      the beam-position monitor (BPM) system has been renovated. The new system was
      designed to enable precise and fast measurements to correct the closed-orbit
      distortion (COD), as well as to feed back the orbit position during user runs.
      There are 42 BPMs newly installed, amounting to a total of 65 BPMs. All of the
      BPMs are calibrated on the test bench using a coaxially strung metallic wire. The
      measured electrical offsets are typically 200 micro m in both directions, which
      is 1/2-1/3 of those of the old-type BPMs. In the signal-processing system, PIN
      diode switches are employed in order to improve reliability. In the fastest mode,
      this system is capable of measuring COD within about 10 ms; this fast acquisition
      will allow fast suppression of the beam movement for frequencies up to 50 Hz
      using a global feedback system.

PMID- 15263600
TI  - Beam-position monitors in the X-ray undulator beamline at PETRA.
AB  - At the 12 GeV storage ring PETRA, the first synchrotron radiation beamline uses a
      4 m-long undulator. The beamline, with a length of 130 m between source and
      sample, delivers hard X-ray photons usable up to 300 keV. The photon beam has a
      total power of 7 kW. Combined with the high brilliance, the powerful beam is very
      critical for all beamline components. Copper, located at a distance of 26 m, hit
      by the full undulator beam, melts within 20 ms. Different monitors are described
      for stable, safe and reliable operation of beam and experiments.

PMID- 15263601
TI  - Electronics for SPring-8 X-ray beam monitors.
AB  - A sensitive current-measuring system is required to construct a highly sensitive
      X-ray beam-position monitor (XBPM). A current-voltage converter (I/V) which can
      measure currents between 0.1 nA and 10 mA was designed, and the signal processing
      system of the XBPM was constucted using this I/V. This system was used in
      beamline commissioning. Beam-position data standard deviations of sigma
      approximately 3 micro m for the bending-magnet beamline, and sigma(x)
      approximately 3 micro m and sigma(y) approximately 1 micro m for the insertion
      device beamline were obtained during the beamline commissioning.

PMID- 15263602
TI  - Smart X-ray beam position monitor system using artificial-intelligence methods
      for the Advanced Photon Source insertion-device beamlines.
AB  - At the Advanced Photon Source (APS), each insertion-device (ID) beamline front
      end has two X-ray beam position monitors (XBPMs) to monitor the X-ray beam
      position for both vertical and horizontal directions. Performance challenges for
      a conventional photoemission-type XBPM during operations are contamination of the
      signal from the neighbouring bending-magnet sources and the sensitivity of the
      XBPM to the insertion-device gap variations. Problems are exacerbated because
      users change the ID gap during their operations, and hence the percentage level
      of the contamination in the front-end XBPM signals varies. A smart XBPM system
      with a high-speed digital signal processor has been built at the Advanced Photon
      Source for the ID beamline front ends. The new version of the software, which
      uses an artificial-intelligence method, provides a self-learning and self
      calibration capability to the smart XBPM system. The structure of and recent test
      results with the system are presented in this paper.

PMID- 15263603
TI  - Synthetic diamond-based position-sensitive photoconductive detector development
      for the Advanced Photon Source.
AB  - A novel X-ray beam-position detection device that we call a position-sensitive
      photoconductive detector (PSPCD) is designed to have synthetic diamond as its
      substrate material. We proved that it is feasible to use synthetic diamond to
      make a hard X-ray position-sensitive detector based on the photoconductivity
      principle and that it acts as a solid-state ion chamber. Experiments on different
      PSPCD samples using synthetic diamond with a high-heat-flux white undulator beam,
      as well as with monochromatic hard X-ray beams, have been performed at the
      Advanced Photon Source. Recent test results with the PSPCD in the quadrant
      configuration as an X-ray beam-position monitor and in a multipixel array as an X
      ray beam profiler are presented in this paper.

PMID- 15263604
TI  - Diagnostic front end for BESSY II.
AB  - For BESSY II, synchrotron radiation beam diagnostics will be incorporated in both
      the insertion-device front ends and the dipole-beamline front ends. In order to
      gain a complete picture of the source characteristics, a diagnostic front end has
      been designed and tested for dipole radiation. This consists of (i) a pinhole
      array imaging system, (ii) a double-blade system for the determination of the
      vertical center of gravity of the synchrotron radiation fan, and (iii) a Bragg
      Fresnel multilayer system for the most precise image information about the source
      size and shape.

PMID- 15263605
TI  - Spatio-temporal measurement of beam properties in the PLS diagnostic beamline.
AB  - A diagnostic beamline is being constructed in the PLS storage ring for
      measurement of electron- and photon-beam properties. It consists of two 1:1
      imaging systems: a visible-light imaging system and a soft X-ray imaging system.
      In the visible-light imaging system, the transverse beam size and beam position
      are measured with various detectors: a CCD camera, two photodiode arrays and a
      photon-beam position monitor. Longitudinal bunch structure is also investigated
      with a fast photodiode detector and a picosecond streak camera. On the other
      hand, the soft X-ray imaging system is under construction to measure beam sizes
      with negligible diffraction-limited error. The X-ray image optics consist of a
      flat cooled mirror and two spherical focusing mirrors.

PMID- 15263606
TI  - Source, optical and detector requirements for X-ray diffraction and scattering.
AB  - The standard curves used to describe the properties of synchrotron radiation
      sources usually consist of a plot of the flux or brightness from the source as a
      function of wavelength. These curves are useful for the case where a high flux or
      brightness is required. Many experiments do not fall into this category. An
      alternative description of the source requirements is to provide the maximum flux
      into the phase space volume defined by the specimen. A diagrammatic way of
      illustrating how this can be achieved is derived. This illustrates how the
      source, optics and detectors can be matched to the requirements of a particular
      experiment. This approach is illustrated using, as examples, a beamline on the
      SRS and two beamlines planned for DIAMOND, the proposed new UK third-generation
      source.

PMID- 15263607
TI  - Optical design of the U7 undulator beamline at the Pohang Light Source.
AB  - The first insertion-device beamline at the Pohang Light Source is designed for
      high-resolution spectroscopy and spectromicroscopy. The beamline will contain a
      variable-included-angle plane-grating monochromator (VIA-PGM) using a grating
      substrate which has seven different grooves with different depths. The advantages
      of this scheme will be the fixed exit-slit position and the mechanical stability
      of the grating scan mechanism while changing the photon energy range. The
      beamline is designed to cover the photon energy range 20-2000 eV. The estimated
      spectral resolution, E/DeltaE, is above 8000 in the photon energy range below 500
      eV, and above 4000 for the remaining photon energy range. The estimated flux at
      the end-station is of the order of 10(12) photons s(-1) (0.1% bandwidth)(-1).

PMID- 15263608
TI  - The multicrystal monochromators of the TROIKA beamline at ESRF.
AB  - A multicrystal UHV monochromator equipped with up to four different monochromator
      crystals, which can be exchanged in situ, is described. The monochromator is
      designed as a transmission monochromator in horizontal scattering geometry
      allowing the 'quasi-white' beam, after transmission through X-ray-transparent
      diamond or beryllium monochromator crystals, to be utilized in independent
      downstream stations.

PMID- 15263609
TI  - A uniformly cleaved epitaxically grown diamond crystal for synchrotron radiation.
AB  - A homoepitaxic single-crystal diamond (111) film grown by microwave-assisted
      chemical vapour deposition (CVD) and fractured along the [110] directions to form
      small triangles was investigated by X-ray double-crystal topography. The X-ray
      topographic image showed that all parts of the cleaved CVD diamond film sections
      uniformly reflected X-rays at the peak position of the rocking curve, which was
      measured in the Bragg case. Furthermore, no bending effect was observed and the
      CVD diamond film appeared to be more perfect than and showed higher integrated
      intensity than the natural diamond substrate.

PMID- 15263610
TI  - Optical design of the general-purpose Spanish X-ray beamline for absorption and
      diffraction.
AB  - This paper describes the optical design of the general-purpose Spanish beamline
      for absorption and diffraction (SpLine), which will be installed on a bending
      magnet port of the ESRF. This beamline is planned to cover the needs of the
      Spanish synchroton radiation community with broad scientific fields of interest,
      covering physics, chemistry, materials science and biology. By using the
      advantages of a wide front end (9 mrad), the Spanish beamline will be split into
      two branches. Both branches will be equipped with focusing optics and
      experimental stations. Thus, each branch can be operated simultaneously and
      independently from each other. One branch (A) will have two experimental
      stations, one for high-resolution powder diffraction (HRPD) and the other for X
      ray absorption spectroscopy (XAS) and X-ray standing waves (XSW). The other
      branch (B) will have facilities for macromolecular crystallography and for single
      crystal diffraction analysis, including that of surfaces and interfaces, as well
      as an X-ray diffraction/scattering camera for non-crystalline specimens.

PMID- 15263611
TI  - Rotated-inclined double-crystal monochromator for synchrotron radiation:
      aberration and its compensation.
AB  - A rotated-inclined double-crystal X-ray monochromator was designed for high-power
      undulator beamlines for SPring-8 to reduce the impinging radiation power density.
      Recently, it has been shown that an inclined double-crystal monochromator suffers
      from a certain type of geometrical aberration that may be relatively easily
      compensated. In this paper, it is shown that a similar aberration exists also in
      the case of rotated-inclined monochromators and that as in the inclined case the
      aberration may also be compensated.

PMID- 15263612
TI  - A high-performance double-crystal monochromator soft X-ray beamline.
AB  - A high-performance double-crystal-monochromator soft X-ray (DCMSX) beamline has
      been constructed at the Synchrotron Radiation Research Center (SRRC). This
      beamline delivers monochromatic photon beams with energies from 1 to 9 keV and a
      resolving power (E/DeltaE) of up to 7000. This beamline provides users with an
      opportunity to study many important materials, such as high-T(c) superconductors,
      magnetic materials, catalysts, super-alloy compounds etc. Excellent EXAFS and
      NEXFS spectra have been routinely obtained from this beamline. Several
      interesting research projects are currently being conducted at this beamline. All
      the results show that this beamline has been constructed to meet its design
      goals.

PMID- 15263613
TI  - Finite-element study of a toothed-crystal monochromator.
AB  - A toothed-crystal monochromator, proposed in previous papers, is a modification
      of an inclined monochromator, which reduces the impinging radiation power density
      on the surface of a crystal for broad synchrotron radiation beams. The surface of
      the monochromator has a triangular toothed structure oriented in such a way that
      it represents an inclined monochromator. Finite-element analysis of thermally
      induced deformation was performed for a particular shape of toothed crystal and
      for a flat crystal of the same average thickness. It was estimated that the
      toothed-crystal monochromator may provide 70% higher radiation power than the
      flat-crystal monochromator.

PMID- 15263614
TI  - X-ray diffraction with a Bragg angle near pi/2 and its applications.
AB  - X-ray dynamical diffraction phenomena at a Bragg angle near pi/2 are studied. The
      X-ray transmissivity as well as the reflectivity from the (991) lattice plane of
      a silicon thin plate is observed. It agrees fairly well with the diffraction
      pattern calculated on the basis of the Darwin approach. The possibility is
      discussed whether a set of two crystal plates arranged face to face, in which the
      diffraction condition with a Bragg angle near pi/2 is satisfied, may be used as a
      very high resolution monochromator.

PMID- 15263615
TI  - A new water-cooled and doubly bent crystal monochromator for Compton scattering
      experiments.
AB  - The design and performance of a new water-cooled and doubly bent crystal
      monochromator for Compton scattering experiments are described. Its mechanical
      system is similar to that of a usual bent cylindrical X-ray mirror. A monolithic
      Si (111) crystal is mounted on a water-cooled and cylindrically polished copper
      crystal holder with liquid Ga-In alloy between them in order to obtain good
      thermal and mechanical contact. The sagittal bending radius of the holder, R(s),
      is 508 mm. The holder is mounted on a mechanical bender making a meridian radius,
      R(m), of 596 m. The performance of the monochromator, which has been installed at
      the Photon Factory Accumulator Ring beamline NE1, is as follows. The focused beam
      size, flux and energy resolution for 60 keV X-rays are 0.5 mm in height and 2.0
      mm in width, 5 x 10(12) photons s(-1) and about 60 eV, respectively. The new
      monochromator gives one order higher brightness at the sample position and also
      better energy resolution than the previous monochromator. The overall momentum
      resolution for high-resolution Compton scattering experiments becomes 0.08 atomic
      units, and the background can be reduced by a third, because it is possible to
      insert a fine slit after the analyser crystal without losing any Compton
      scattering signal.

PMID- 15263616
TI  - Development of an (X, eX) spectrometer for measuring the energies of the
      scattered photon and recoil electron.
AB  - The design and performance of a new spectrometer for coincidence measurements
      between the Compton scattered photon and the recoil electron are described.
      Coincidence measurements give direct information on the three-dimensional
      electron momentum density (EMD) of condensed matter. The present spectrometer
      measures energy spectra of both the photon and the electron. The energy spectrum
      of electrons is measured by a time-of-flight method using single-bunch operation
      at the Photon Factory Accumulator Ring (PF-AR). The energy resolution obtained
      for the recoil electron is 190 eV, which is better than that of the photon
      detector, so that a momentum resolution of the three-dimensional EMD of 0.3
      atomic units can be achieved.

PMID- 15263617
TI  - Position of exit X-rays from rotated-inclined double-crystal monochromators.
AB  - The rotated-inclined double-crystal monochromator (RIDCM) has been adopted to
      reduce the heat load from third-generation undulator radiation. The position of
      the exit X-rays from RIDCM has been calculated as a function of X-ray energy on
      the basis of diffraction theory including refraction effects. The results show
      that the positions of the exit X-rays vary over a wide range due to asymmetric
      reflection. Methods of fixing the exit position in RIDCM are also discussed.

PMID- 15263618
TI  - Adaptive indirectly cooled monochromator crystals at HASYLAB.
AB  - The high-heat-load monochromator, based on the HASYLAB (Hamburger
      Synchrotronstrahlungslabor) 'Torii' design, has been used successfully for 2
      years at the BW2 wiggler beamline. The bowing of the reflecting surface induced
      by the heat load and water pressure is compensated mechanically. This is achieved
      by mounting the specially shaped crystal in a bending mechanism and by heat
      transfer from the directly water-cooled crystal. We present the latest step in
      the development of this design. The piezoceramic-driven actuators are replaced by
      actuators based on the thermal expansion of copper rods. The direct water cooling
      of the crystal is replaced by a safer indirect water-cooling scheme.
      Characterization results of the crystal are presented. The Si(111) rocking-curve
      width at 9.5 keV was measured to be 8.3 arcsec under 500 W heat load.

PMID- 15263619
TI  - Microcontroller-based servo for two-crystal X-ray monochromators.
AB  - Microcontrollers have become increasingly easy to incorporate into instruments as
      the architectures and support tools have developed. The PIC series is
      particularly easy to use, and this paper describes a controller used to stabilize
      the output of a two-crystal X-ray monochromator at a given offset from its peak
      intensity position, as such monochromators are generally used.

PMID- 15263620
TI  - Focusing and reflection by a bent crystal for high-energy synchrotron radiation.
AB  - The focusing properties and resolution of a doubly bent crystal in the Bragg case
      have been analytically studied from a geometrical viewpoint. Simulation using the
      Takagi-Taupin equations was also performed for singly bent crystal reflections to
      study the reflectivity. The critical radius of curvature for changing from
      dynamical to kinematical diffraction is calculated to be of the order of a few
      tens of metres for an Si 400 reflection of 110 keV X-rays.

PMID- 15263621
TI  - Soft X-ray multilayer beam splitters.
AB  - A semitransparent Mo/Si multilayer beam splitter with a completely self-standing
      active area (10 x 10 mm) and a flatness of 1.1 nm (r.m.s.) was fabricated. The
      influence of the roughness of the membrane substrate on the reflectivity of a
      beam splitter was investigated for different materials and deposition schemes.
      Precise control of multilayer stress to give a slightly tensile state not only
      enables the fabrication of a large and flat reflection surface, but also makes it
      possible to etch away the supporting membrane and obtain a completely self
      standing structure. The performance evaluation using synchrotron radiation
      revealed that the fabricated beam splitter works as a one-to-one beam splitter
      whose reflectivity and transmittance are both 27% (s-polarization, 45 degrees,
      lambda = 13.4 nm).

PMID- 15263622
TI  - Characterization of substrates for use in X-ray multilayer optics.
AB  - The optical performance of platinum-carbon multilayers deposited onto different
      substrates has been examined. Specular reflectivity and non-specular diffuse
      scattering were measured to study the replication of substrate roughness into the
      multilayer structure. Surface topography was measured before and after deposition
      using a scanning probe microscope and a mechanical profiler.

PMID- 15263623
TI  - A simple accurate method of alignment of beamline optics with the use of EUV
      multilayer polarizers.
AB  - A simple alignment method is proposed, which enables the alignment of beamline
      optics of a bending section accurately, relying on the linear state of
      polarization of synchrotron orbital radiation rather than the beam intensity. The
      method utilizes extreme UV (EUV) multilayers as a compact polarization monitor
      detecting unwanted vertical polarization components. The proposed method was
      found to be far more sensitive than that relying on the maximum intensity.
      Another advantage is the insensitivity to surface contamination, such as an
      irradiation mark on the mirror degrading reflectance. A design example is
      presented for use around a photon energy of 370 eV along with an experimental
      example at a photon energy of 97 eV.

PMID- 15263624
TI  - Bent-crystal monochromators for high-energy synchrotron radiation.
AB  - Two kinds of monochromators covering the energy ranges 100-150 keV and
      approximately 300 keV have been designed for inelastic (Compton) scattering
      experiments at the elliptical multipole wiggler beamline, BL08W, of SPring-8.
      Finite-element analyses using ANSYS for bent crystals indicate that thermal
      problems are not serious for the 300 keV monochromator, while an energy spread of
      about 10(-3) for the 100-150 keV monochromator is possible in the centre of the
      crystal. Detailed calculations of X-ray interaction with the silicon crystal were
      performed. The results show that Compton scattering is a dominant process and
      deposits about 100 W continuously.

PMID- 15263625
TI  - Fabrication of Mo/Al multilayer films for a wavelength of 18.5 nm.
AB  - This paper reports the fabrication and evaluation of Mo/Al and Mo/Si multilayer
      films (MLs) for a wavelength of 18.5 nm. Calculated reflectivities of Mo/Al MLs
      at an incident angle of 10 degrees were about 7% higher than those of Mo/Si MLs.
      MLs were fabricated using an RF-magnetron sputtering deposition system. The
      measured reflectivity of Mo/Al MLs was 33.5%. The cause of the decreasing
      reflectivity was supposed to be the surface and interfacial roughness. In the
      surface observation utilizing atomic force microscopy, the surface roughness of
      Mo/Al MLs was dominated by the Al layer. Therefore, the conditions for
      fabricating Al films were optimized.

PMID- 15263626
TI  - (Ta/Si) multilayer as a wide-bandpass monochromator material.
AB  - Specular and non-specular X-ray reflectivity intensities of a (Ta/Si)(60)
      multilayer sample were measured to characterize its interface structure. Since
      the multilayer has a good reflectance at its multilayer peaks, its performance as
      a wide-bandpass monochromator for X-ray scattering experiments of polymers has
      been tested.

PMID- 15263627
TI  - Design and fabrication of highly heat-resistant Mo/Si multilayer soft X-ray
      mirrors with interleaved barrier layers.
AB  - Introducing interleaved carbon barrier layers improves the heat-resistance of
      Mo/Si multilayers. The soft X-ray reflectivities of the multilayers were
      calculated, and the effects of heating on both the reflectivities and layer
      structures of Mo/Si multilayers with and without barrier layers were investigated
      using X-ray diffraction and transmission electron microscopy. The results show
      that, for applications using intense soft X-ray beams, Mo/Si multilayers with
      interleaved carbon barrier layers are better mirrors than Mo/Si multilayers
      because they have much better heat resistance and almost the same soft X-ray
      reflectivity as the Mo/Si multilayers.

PMID- 15263628
TI  - Fabrication and characterization of multilayer supermirrors for hard X-ray
      optics.
AB  - Multilayer supermirrors stacked with three sets of Pt/C combinations have been
      fabricated on a flat float-glass and conical replica foil mirror using a
      magnetron DC sputtering system, and applied to X-ray optical systems in the hard
      X-ray region. The design of the supermirror is optimized to obtain the highest
      integrated reflectivity in the energy band and at the grazing angle concerned. X
      ray reflectivities of 30% in the 25-35 keV band at an incidence angle of 0.3
      degrees were obtained.

PMID- 15263629
TI  - Design and performance of a multilayered mirror monochromator in the low-energy
      region of the VUV.
AB  - For the energy region from tens to hundreds of electron volts, the multilayered
      mirror (MLM) monochromator has never been realized due to the difficulty of
      reducing the background noise of the total reflection component, in spite of its
      usefulness in synchrotron radiation experiments. In this work, a double-crystal
      type MLM monochromator equipped with a thin-film filter has been designed on the
      basis of trial fabrication of the mirror-driving system and of Mo/Si and Mo/C
      MLMs; its performance has been evaluated by calculating its output photon flux.
      It is shown that by using the MLMs at low incident angles, combined with an
      appropriate thin-film filter, it is possible to make a practical monochromator
      with high output photon flux and low background noise.

PMID- 15263630
TI  - Use of YB(66) as monochromator crystals for soft-energy EXAFS.
AB  - YB(66)(400) crystals present a new advance in monochromator crystals suitable for
      use at energies below 2 keV. In this paper a comparison of their performance with
      that provided by the more usual beryl and quartz crystals, which cover the same
      energy range, is presented. In general, the YB(66) crystals are much superior;
      however, they do exhibit a pair of large 'crystal glitch'-type features in the
      1380-1440 eV region. These fall in the Mg K-EXAFS region and so can present a
      serious problem in studies of this edge for a wide range of materials. An
      important class of materials so afflicted are magnesium-substituted
      aluminophosphate molecular sieves (zeolites), which are used in many
      applications, in particular as solid acid catalysts for conversion of methanol to
      hydrocarbon.

PMID- 15263631
TI  - Optimization strategies for XUV monochromators.
AB  - The techniques of monochromator optimization are reviewed, and it is shown that
      until recently only a few of the available parameters were used at the same time.
      Efficient optimization can be performed numerically. The computation method
      developed at LURE is explained and an example is given. Extension and development
      of the method are outlined.

PMID- 15263632
TI  - A unique high-performance wide-range (10-1500 eV) spherical grating monochromator
      beamline.
AB  - A wide-spectral-range high-performance 6 m-spherical grating monochromator (6 m
      SGM) beamline has been designed and is under construction at SRRC. Two different
      entrance slits, instead of additional mirrors, are used to optimize the overall
      performance. Six gratings are used to cover photon energies from 10 to 1500 eV.
      Movable entrance slits and bendable vertical focusing mirrors are used to enhance
      further the beamline performance. A bendable horizontal focusing mirror is used
      to improve the resolution and to focus the photon beam at the experimental
      station immediately after the exit slit. Several end-stations can be installed at
      the same time to utilize the beam time fully. The expected energy-resolving
      power, with both slit openings set at 10 micro m, is up to 15 000 and 40 000 for
      the high- and low-energy branches, respectively. A photon flux of 1 x 10(11)
      photons s(-1) can be obtained with an energy-resolving power of 20 000.

PMID- 15263633
TI  - Performance of the YB(66) soft X-ray monochromator crystal at the wiggler
      beamline of the UVSOR facility.
AB  - Soft X-ray spectra have been measured using a pair of YB(66)(400) monochromator
      crystals at the double-crystal monochromator beamline BL7A of the UVSOR facility,
      where the wiggler radiation has a magnetic field of 4 T. Deformation of the
      YB(66) crystal due to heat load from the synchrotron radiation is almost
      negligible. The photon flux is about 10(8) photons s(-1) (100 mA)(-1) in the
      energy region 1.2-2 keV and the energy resolution is 0.7 +/- 0.1 eV around hnu =
      1.5 keV. These results show that the YB(66) crystal is suitable for use as a
      monochromator crystal. Its application to soft X-ray spectroscopy is discussed.

PMID- 15263634
TI  - A soft X-ray (80-1500 eV) grazing-incidence monochromator with varied-line
      spacing plane gratings at PF-BL-11A.
AB  - The design and performance of a new soft X-ray beamline BL-11A at the Photon
      Factory (PF) are presented. A Hettrick-type grazing-incidence monochromator
      equipped with three varied-line-spacing plane gratings was designed and
      constructed at a bending-magnet source of the PF 2.5 GeV storage ring. An 800
      lines mm(-1) laminar grating produced by aspheric-wavefront holographic recording
      optics, as well as a mechanically ruled blazed one, were tested. A resolving
      power of more than 4500 was achieved at 400 eV with either grating, and
      approximately 10(10) photons s(-1) are available at a resolving power of 2000.
      High photon flux enables low-concentration samples, such as surface adsorbates,
      to be studied. A simple scanning mechanism for a wide energy range is quite
      useful for EXAFS measurements on light elements such as C, N and O.

PMID- 15263635
TI  - Transmission multilayer polarizers for use in the 55-90 eV region.
AB  - Free-standing Al/YB(6) and Mo/Si transmission multilayer polarizers have been
      developed for use in the photon energy regions 55-72 eV and 72-90 eV,
      respectively, to improve the degree of polarization of synchrotron radiation
      light from beamline monochromators. The polarizance (polarizing ability) and
      transmittance of the Al/YB(6) multilayer for unpolarized light at 64 eV were 77%
      and 3.4%, respectively, and the polarizance and transmittance of the Mo/Si
      multilayer at 80 eV were 79% and 2.2%, respectively. By using the Mo/Si
      polarizer, the degree of polarization of the monochromated light at BL8B1 of
      UVSOR was increased from 95 to 99% in the 78-84 eV region.

PMID- 15263636
TI  - High-performance EUV/soft X-ray ellipsometry system using multilayer mirrors.
AB  - A high-performance EUV/soft X-ray ellipsometry system using multilayer mirrors
      has been developed. A couple of multilayer mirrors were used for the polarizer,
      and two multilayer mirrors were used for the rotating analyser. The multilayer
      mirrors were optimized to obtain a medium extinction of about 2000. An extinction
      ratio of the polarizer up to 10(4) can be achieved by using two multilayer
      mirrors, and the calculated reflectivity was more than 35%. The calculated error
      of the optical elements reveals that the error of the polarizer and misalignment
      optical parts is mainly of the first order, and that of the analyser is of the
      second order.

PMID- 15263637
TI  - Transmission-type X-ray linear polarizer with perfect crystals.
AB  - Even though conventional X-ray polarizers with multiple-reflection channel-cut
      structures perform well, they suffer from the disadvantage that the polarized
      beam is non-stationary as the energy is scanned. In this paper the possibility of
      using a thin Bragg reflector as a polarizing filter is investigated, so that the
      transmitted beam (rather than the Bragg-reflected beam) is used. Consequently,
      the position and direction of the transmitted beam are unchanged as the energy is
      changed, or even when the polarization direction to be filtered out is changed.
      Theoretical considerations as well as experimental results on the performance
      characteristics of the proposed transmission-type X-ray linear polarizer are
      presented. A polarization ratio, defined as I(H)/I(V), higher than 10(5) was
      obtained.

PMID- 15263638
TI  - A new compact spin- and angle-resolving photoelectron spectrometer with a high
      efficiency.
AB  - A portable spin- and angle-resolving photoelectron spectrometer has been
      constructed, equipped with a newly developed compact retarding-potential Mott
      scattering electron spin polarimeter with an efficiency of 1.9 x 10(-4) for a
      gold target. Based on Monte Carlo calculations for the spin-dependent electron
      scattering process and electron ray-tracing calculations, a novel design of the
      retarding-field electron optics with 0.59 sr collection solid angle for scattered
      electrons has been accomplished. Utilizing this spectrometer, the spin- and angle
      resolved photoelectron spectra have been measured and the spin-dependent
      electronic structure of Ni(110), Ni(110)-p(2 x 1)O and Ni(110)-c(2 x 2)S along
      the ${?overline {?Gamma S}}$ line of the Ni(110) surface Brillouin zone have been
      studied.

PMID- 15263639
TI  - Stretched polymers for X-ray linear and circular polarization.
AB  - X-ray linear dichroism at the iodine K-edge of Polaroid H-sheet is explored with
      a view to using stretched polymers for X-ray linear-polarization analysis. The
      potential use of such materials as phase plates for generating elliptically
      polarized beams is also considered.

PMID- 15263640
TI  - A plane-grating monochromator for circularly polarized undulator radiation at
      BESSY II.
AB  - At BESSY II, a third-generation 1.7 GeV storage ring is under construction. A
      planar elliptical undulator will be installed as a source of X-rays that have a
      high degree of circular polarization. Radiation in the first, third and fifth
      harmonics will cover the energy range 87-1330 eV. The beamline will essentially
      consist of a plane-grating monochromator working with collimated light in the
      dispersion plane. A single set of optical elements can be used to handle the two
      angularly separated beams of opposite helicity from the double undulator. The
      degree of circular polarization ranges from 73 to 100%, and a flux of up to 5 x
      10(13) photons s(-1) (100 mA)(-1) can be achieved. A maximum spectral resolution
      of about 13 000 will be possible at 100 eV using a 20 micro m slit.

PMID- 15263641
TI  - Nanosecond-resolved XMCD on ID24 at the ESRF to investigate the element-selective
      dynamics of magnetization switching of Gd-Co amorphous thin film.
AB  - The one-bunch filling mode of the ESRF is combined with a microcoil to generate a
      pulsed-magnetic-field pump phased with respect to the probe that is given by the
      bunch of photons emitted each turn (357 kHz). Nanosecond-resolved X-ray magnetic
      circular dichroism (XMCD) is carried out. Besides the microcoil, the two other
      key-elements are the energy-dispersive XAS spectrometer, which yields parallel
      data acquisition, and the diamond-based quarter-wave plate, which tunes the
      helicity of the photon alternatively left and right.

PMID- 15263642
TI  - A scattering filter for energy-dispersive optics.
AB  - A filtering technique to remove parasitic scattering from X-ray absorption
      spectra that are acquired in energy-dispersive mode has been developed and tested
      at the European Synchrotron Radiation Facility. The improved set-up removes small
      angle scattering of the sample or the windows of sample cells which may spoil the
      energy resolution or reduce the intensity of prominent features in the absorption
      spectrum, such as the white line at the Pt L(III) edge. The sample is placed
      behind the curved monochromator and between two plane perfect crystals in the
      Bonse-Hart configuration. The dispersion of the Bonse-Hart double-crystal camera
      is matched to the dispersion of the curved monochromator by inclining the
      scattering planes of the two optical elements against each other.

PMID- 15263643
TI  - Absolute calibration of a soft X-ray spectrograph for X-ray laser research using
      white beam.
AB  - Absolute calibration of a soft X-ray spectrograph has been performed using a
      white beam of synchrotron radiation. The calibrated spectrograph was a flat-field
      grazing-incidence spectrograph with an X-ray CCD detector for X-ray laser
      research. Absolute sensitivity of the spectrograph system can be obtained from
      transmitted spectra using filters made of several different materials, each
      providing an absorption-edge wavelength standard. The absolute sensitivity
      determined in this work shows nearly the same behaviour with wavelength as that
      in another calibration experiment using a laser-produced plasma as an X-ray
      source.

PMID- 15263644
TI  - Beamline for calibration of transfer standard light sources in the UV and VUV
      regions.
AB  - A beamline which serves for calibrating transfer standard light sources
      (deuterium lamps, excimer lamps, Xe lamps etc.) in the UV and VUV regions is
      being constructed. The synchrotron radiation from the electron storage ring TERAS
      (750 MeV) is used as a primary standard of spectral radiant intensity. In order
      to use synchrotron radiation as a primary standard, the electron beam and
      synchrotron radiation beam parameters need to be evaluated. Uncertainties of
      synchrotron radiation flux evaluated by measurements of the magnetic flux
      density, the position of the electron orbital plane, the electron beam size and
      the distance from the synchrotron radiation tangent point to the detector system
      are expected to be about 0.003, 0.01, 0.05 and 0.1%, respectively.

PMID- 15263645
TI  - Calibration of space-resolving VUV and soft X-ray spectrographs for plasma
      diagnostics.
AB  - Vacuum ultraviolet (VUV) and soft X-ray measurements are important means of
      diagnosing impurities in magnetically confined plasmas used in fusion research.
      Recently, space- and time-resolving flat-field VUV (150-1050 A) and soft X-ray
      (20-350 A) spectrographs have been constructed by using aberration-corrected
      concave gratings with varied-spacing grooves which give a wide simultaneous
      spectral coverage on a microchannel-plate intensified detector. Calibration
      experiments have been performed at beamlines 11A and 11C at the Photon Factory of
      the High Energy Accelerator Research Organization. The relative efficiency of the
      VUV spectrograph has been measured for P-polarization geometry in the
      spectrograph. In the soft X-ray spectrograph, efficiencies have been obtained for
      several different points of irradiation on the grating along the groove direction
      and for two (S and P) polarization geometries.

PMID- 15263646
TI  - Construction and performance test of SGM-TRAIN at UVSOR.
AB  - A new spherical-grating monochromator with translational and rotational assembly
      including a normal-incidence mount (SGM-TRAIN) has been constructed at BL5A of
      the UVSOR facility. The SGM-TRAIN is an advanced version of a constant-length SGM
      with the following improvements: (i) a wide energy range of 5-250 eV; (ii) a high
      resolving power; (iii) use of linear and circular polarization; (iv) reduction of
      second-order light; (v) two computer-controlled driving modes. Part of the
      performance tests are reported along with a detailed description of the design.

PMID- 15263647
TI  - Plane-grating monochromator at BESSY II using collimated light.
AB  - At the German synchrotron radiation facility BESSY II, the VUV photon energy
      range between 15 and 600 eV is covered by the first, third and fifth harmonics of
      the U125 undulator. The beamline connected to this source is a plane-grating
      monochromator (PGM) with a variable deviation angle. The plane grating is
      illuminated by collimated radiation, allowing very flexible use of the
      monochromator. Depending on users' demands, it can be operated at high spectral
      resolution, high-order suppression or in high-flux mode, simply by software
      control.

PMID- 15263648
TI  - UV emission spectrometer using a non-periodic grating.
AB  - A UV emission spectrometer using a non-periodic spherical grating has been
      designed, which can be attached to the linear or helical undulator beamlines of
      the HiSOR light source at the Hiroshima Synchrotron Radiation Centre. The useful
      range of emitted photons from 10 to 100 eV is covered by two gratings with
      nominal groove spacings of 1/600 and 1/1200 mm. The energy resolution with a 100
      micro m entrance slit width and the 1/600 mm grating is better than 0.2 eV below
      50 eV.

PMID- 15263649
TI  - Design of an 18 m spherical-grating monochromator at UVSOR.
AB  - An 18 m spherical-grating monochromator with high resolution and high photon flux
      has been developed at the bending-magnet beamline BL2B2 of the UVSOR facility in
      the Institute for Molecular Science. The monochromator is designed to cover the
      energy range 20-200 eV by using three gratings: G1 (2400 lines mm(-1), R = 18 m)
      at 80-200 eV; G2 (1200 lines mm(-1), R = 18 m) at 40-100 eV; G3 (2400 lines mm(
      1), R = 9.25 m) at 20-50 eV. A resolving power of 5000 and a photon flux of more
      than 10(10) photons s(-1) are expected at a 100 mA ring current. A small
      including angle of 140 degrees is adopted for G3 and two plane mirrors coated
      with aluminium are located between G3 and the exit slit as optical filters. These
      geometrical devices may contribute significantly to the reduction of the high
      order lights.

PMID- 15263650
TI  - High-resolution spherical grating monochromator for the undulator beamline (BL
      16B) at the Photon Factory.
AB  - The design and performance of a 24 m high-resolution spherical grating
      monochromator (H-SGM) for the undulator beamline (BL-16B) at the Photon Factory
      are described. With three interchangeable gratings of 400, 900 and 2000 lines mm(
      1), the H-SGM is designed to cover the photon energy range 40-600 eV. With a
      resolving power of approximately 2000 in the photon energy range 40-530 eV, more
      than 10(11) photons s(-1) have been measured. The best resolutions obtained so
      far, at a substantially lower photon flux, are greater than 10 000 at 250 eV and
      8000 at 400 eV

PMID- 15263651
TI  - A plane-grating monochromator beamline for the PTB undulators at BESSY II.
AB  - At the BESSY II storage ring, the Physikalisch-Technische Bundesanstalt (PTB)
      will operate insertion devices dedicated to radiometric use. One branch of the
      appendant beamline system will be equipped with a grazing-incidence
      monochromator, described here. The monochromator concept is based on a plane
      grating operated in parallel light; therefore exact focusing is maintained for
      all photon energies irrespective of the angular setting at the grating. The
      monochromator has been optimized for small higher-order transmittance and high
      power throughput, as required by radiometric applications in the wide photon
      energy range from 20 eV to 1900 eV.

PMID- 15263653
TI  - Recent performance of the Photon Factory gratingcrystal monochromator station BL
      1A in the soft X-ray region.
AB  - This paper describes the recent performance of the Photon Factory beamline 1A
      with InSb(111) crystals used as the diffracting elements of the grating/crystal
      monochromator for monochromatizing soft X-rays. Pt-coated collimating and
      focusing mirrors located upstream and downstream of the monochromator have
      recently been replaced with Ni-coated mirrors in order to remove absorption
      structures at the Pt M-edges from output spectra in the soft X-ray region. Output
      spectra without the absorption structures and with higher intensity in the range
      2000-3400 eV were obtained by using the Ni-coated collimating and focusing
      mirrors.

PMID- 15263652
TI  - Higher-order suppression in diffraction-grating monochromators using thin films.
AB  - Although a continuously tuneable source of photons is a very desirable feature of
      synchrotron radiation it has one main drawback: the contamination of the photon
      beam by higher-order diffracted light. Several elements have absorption edges
      which lie between 10 and 200 eV, a range prone to high second- and third-order
      content in XUV monochromators. They can, therefore, be used as transmission
      filters to reduce this higher-order content. This paper describes the use of thin
      filters to reduce the higher-order content in diffraction-grating monochromators.
      Their suppression efficiency, transmission and ageing have been characterized
      using photoelectron spectroscopy and compared with calculated values. The effect
      of oxide contamination on their performance has been assessed. Filters are now
      installed on eight XUV beamlines and have been in routine use for several years.

PMID- 15263654
TI  - Components for the X-ray radiometry beamline at BESSY II.
AB  - Optical components for the X-ray radiometry beamline of the Physikalisch
      Technische Bundesanstalt at BESSY II were investigated at BESSY I. Reflectometry
      measurements on different mirror coatings were used to calculate their capability
      to suppress higher-order radiation. An MgF(2) coating proved to be best suited
      for photon energies below 4 keV. The reflectance of silicon (111) monochromator
      crystals at low photon energies around 2 keV was homogeneous within +/-1%. In a
      test at a superconducting wavelength shifter the cooling system for the first
      crystal was shown to cope with the absorbed power of 14 W.

PMID- 15263655
TI  - Electron-beam writing of large-area Fresnel zone plates.
AB  - High-resolution X-ray microscopy requires advanced fabrication technology for
      Fresnel zone plates (FZPs). As the resolution of an FZP depends on the width of
      the outermost zone, fine zone patterns for objective lenses have to be
      replicated. On the other hand, to achieve highly condensed X-ray beams by using
      FZPs for condenser lenses, large-field replication is required. A method of
      pattern replication of FZPs for X-ray microscopy is reported. Utilizing a 30 keV
      electron-beam writing tool and an FZP-generation computer program, FZP patterns
      for a condenser lens 1 mm in diameter with an outermost-zone width of 0.2 micro m
      and for an objective lens 0.5 mm in diameter with an outermost-zone width of 0.1
      micro m were replicated.

PMID- 15263656
TI  - Ti/Al multilayer zone plate and Bragg-Fresnel lens.
AB  - By using a helicon plasma sputtering technique, a one-dimensional Ti/Al
      multilayer zone plate with an outermost layer width of 76 nm has been
      successfully fabricated. A Bragg-Fresnel lens has been made by combining this
      zone plate with a Ge(422) crystal. Comparison of the Ti/Al multilayer zone plate
      with the Ag/Al zone plate is discussed in terms of focusing efficiency.

PMID- 15263657
TI  - Multi-segmented piezoelectric mirrors as active/adaptive optics components.
AB  - The angular acceptance of piezoelectric (Pzt) bimorph mirrors is limited by the
      maximum length of commercially available Pzt ceramic plates. To overcome this
      limit and manufacture longer devices, several (2n + 1) 150 mm-long bimorph Pzt
      stacks were assembled side-to-side. Two prototype mirrors, 450 (n = 1) and 750 (n
      = 2) mm long, were designed, assembled, polished and optically characterized.
      They are fully UHV compatible and are now installed in the monochromatic section
      of the ESRF beamlines ID26 and ID32. Both mirrors cover the full range of
      required bending radii (1 km concave-3.5 km convex). Junctions between segments
      do not spoil the optical surface quality. The surface slope error r.m.s. can be
      kept well below 1 arcsec over the full bending range. Adaptive compensation for
      low-frequency figure errors was shown to be easy and reliable. After
      compensation, residual shape errors are of the order of 40 nm r.m.s. over 700 mm.

PMID- 15263658
TI  - A compact mirror manipulator in the SRRC beamline.
AB  - A compact mirror manipulator which has high stiffness and is easily adjustable
      has been developed for new beamlines at SRRC. It consists of a vertical stem to
      support the mirror and allows for six-axis precise positioning. The rotation
      adjustment is designed with a minimum of cross-coupling between adjustments. An
      independent support is fixed to the ground to reduce vibration from the chamber
      and the pump. Some performance test results in vacuum and in atmosphere,
      including vibration, repeatability, long-term drift etc., are described in this
      paper.

PMID- 15263659
TI  - Design optimization of a flexural hinge-based bender for X-ray optics.
AB  - This paper presents a parameter study and design optimization of a flexural hinge
      based bender by use of finite-element modelling and analytical formulation. The
      relationship between the mirror shape and the driving forces, the so-called
      bender driving equation, is established. Various parameters are investigated: the
      material properties, the geometrical parameters, the stress and deformation of
      the mirror and flexural hinge, the residual slope error of the mirror, and the
      resolution required for the actuators. Analysis results have been compared with
      test results for a prototype bender and a silicon mirror (170 x 40 x 10 mm). Both
      analysis and test results confirm the microradian accuracy of the bent mirror.
      Finally, a bender design for short-bending-radius applications is also presented.

PMID- 15263660
TI  - Design of and metrological results from a bent parabolic mirror.
AB  - This article describes the successful design and fabrication of, and metrological
      results from, an elastically bent parabolic mirror. The mirror is equipped with a
      bending structure that allows the mirror to be bent meridionally to a parabolic
      shape. This bent parabolic mirror is the key component of the extremely high
      quality monochromators designed for the SPring-8 figure-8 soft X-ray undulator
      and the 2.0 GeV high-brilliance synchrotron radiation source (VSX).

PMID- 15263661
TI  - Thermal and deformation analyses of side-cooled monochromator mirrors for the
      SPring-8/Figure-8 soft X-ray undulator.
AB  - The numerical results for a bent parabolic mirror monochromator designed for the
      SPring-8/Figure-8 soft X-ray undulator are described. A thermal and structural
      finite-element analysis is presented for side-cooled premirrors of the bent
      parabolic mirror monochromator. Using a ray-tracing code, the effect of the final
      induced figure errors on the performance of the premirror are discussed.

PMID- 15263662
TI  - An assessment of approximating aspheres with more easily manufactured surfaces.
AB  - In designing optical systems for synchrotron radiation, one is often led to
      conclude that optimal performance can be obtained from optical surfaces described
      by conic sections of revolution, usually paraboloids and ellipsoids. The
      resulting design can lead to prescriptions for three-dimensional optical surfaces
      that are difficult to fabricate accurately. Under some circumstances satisfactory
      system performance can be achieved through the use of more easily manufactured
      surfaces such as cylinders, cones, bent cones, toroids and elliptical cylinders.
      These surfaces often have the additional benefits of scalability to large
      aperture, lower surface roughness and improved surface figure accuracy. In this
      paper we explore some of the conditions under which these more easily
      manufactured surfaces can be utilized without sacrificing performance.

PMID- 15263663
TI  - Comparison of monochromators with a bent parabolic mirror and a varied-spacing
      grating for the 2.0 GeV high-brilliance synchrotron radiation source (VSX).
AB  - A design study of monochromators for a 2.0 GeV electron/positron storage ring for
      high-brilliance synchrotron radiation in the vacuum ultraviolet (VUV) and the
      soft X-ray regions is described. Two types of VUV/soft X-ray grazing-incidence
      monochromators, one with a bent parabolic mirror and the other with a varied
      spacing grating, are designed. Without any slope error, the expected resolving
      power of the former is much higher, but the latter is less affected by slope
      errors of the optical elements.

PMID- 15263664
TI  - Ray-tracing analysis of capillary concentrators for macromolecular
      crystallography.
AB  - The use of capillary concentrators as X-ray condensers specifically for
      macromolecular X-ray diffraction experiments using synchrotron radiation is
      evaluated. Monocapillary and polycapillary designs are assessed by ray-tracing
      analysis to evaluate how effectively these capillary concentrators can increase
      the X-ray intensity onto a 50 micro m crystal.

PMID- 15263665
TI  - An eight-position capillary sample spinning stage for the diffractometer at BL20B
      at the Photon Factory.
AB  - An eight-position capillary sample spinning stage has been developed for use in
      conjunction with the versatile vacuum diffractometer (BIGDIFF) at BL20B at the
      Photon Factory. BIGDIFF is often used in its powder diffraction mode using
      powders mounted in capillaries and up to eight imaging plates to record the
      diffraction pattern from the sample. Using the multiple spinning stage a number
      of diffraction patterns can be recorded on the imaging plates if the imaging
      plate cassette is moved behind the Weissenberg screen to a new position after
      exposure of the sample to the beam. Not only is this system more efficient in
      terms of time saved in the pumping-down process, but also it has the advantage of
      allowing the diffraction patterns of standards to be recorded, thereby
      calibrating both the angle scale of the diffractometer and the intensity scales
      of the imaging plates absolutely.

PMID- 15263666
TI  - Optical design for laser Doppler angular encoder with sub-nrad sensitivity.
AB  - A novel laser angular-encoder system has been developed based on the principles
      of radar, the Doppler effect, optical heterodyning and self-aligning multiple
      reflection optics. Using this novel three-dimensional multiple-reflection optical
      path, an increase in resolution of 10 to 20 times has been reached compared with
      commercially available laser Doppler displacement meters or laser interferometer
      systems. With the new angular encoder, sub-nrad resolution has been attained in
      the 8 degrees measuring range in a compact set-up [about 60 (H) x 150 (W) x 370
      mm (L)] for high-energy-resolution applications at the Advanced Photon Source
      undulator beamline 3-ID.

PMID- 15263667
TI  - An electrostrictive drive for fine pitch control in double-crystal
      monochromators.
AB  - Precise control of the pitch angle of the crystals in a double-crystal
      monochromator is essential to preserve their accurate alignment while the
      instrument is scanned. Computer-controlled piezoceramic electrostrictive
      actuators have recently been installed to the top crystal in two monochromators
      at the Daresbury SRS to facilitate this. This complements the coarser control
      provided by the existing stepper motor to give an accurate positioning of the
      crystal alignment over the full rocking-curve width of the crystals. To maintain
      accurate alignment during a scan, a number of servo feedback options have been
      devised. In this paper an analysis of the performance of these drives is
      presented and their utility in a variety of different experimental techniques is
      discussed.

PMID- 15263668
TI  - Manufacturing advances in large grazing-incidence optics.
AB  - The fabrication of large grazing-incidence mirrors imposes needs for special
      fabrication and coating equipment, facilities, and raw materials. The economic
      realization of such optics has been readily accomplished through close
      interactions between the mirror users, the fabricator and the manufacturer of the
      raw material designated as mirror substrate. The manufacture and delivery of a
      1.4 m flat and 1.0 m conical mirror are used to provide examples of recently
      demonstrated manufacturing technologies and effective interactions between
      participating organizations.

PMID- 15263669
TI  - Reconstruction of BL7B for UV, VIS and IR spectroscopy with a 3 m normal
      incidence monochromator.
AB  - The beamline BL7B at the UVSOR facility for solid-state spectroscopy is currently
      under reconstruction. This reconstruction mainly involves the replacement of the
      1 m Seya-Namioka-type monochromator (50-600 nm) with a 3 m NIM (modified version
      of McPherson model 2253), which covers the 50-1000 nm range with three gratings.
      The deviation angle of the gratings is 15 degrees. For linear and circular
      polarization experiments, the beamline optics consist of a two-grazing-incidence
      (87.5 degrees ) pre-mirror system and a normal-incidence (15 degrees ) post
      mirror.

PMID- 15263670
TI  - High-flux and high-resolution spectroscopic facility in the VUV region at Super
      ACO.
AB  - A new spectroscopic facility, consisting of a planar/helical undulator and a 6.65
      m off-plane Eagle monochromator, has been designed. It can supply high-flux and
      high-resolution photons with 'exotic' polarization in the 5-40 eV energy range.
      The astigmatism can be compromised by horizontally focusing the incident
      radiation on the grating. The rotation of a post-focusing toroidal mirror
      compensates for the deviation of the exit beam caused by the grating translation.
      The whole system will be installed at beamline SU5 of SUPER-ACO (0.8 GeV) at the
      beginning of 1998. With a 4300 grooves mm(-1) grating, a resolving power of
      around 10(5) is expected at 20 eV.

PMID- 15263671
TI  - Activities of optical laboratories 1 and 2 at the Photon Factory.
AB  - Recent activities at optical laboratories 1 and 2 at the Photon Factory are
      presented. The activities are (i) construction of optical laboratory 1, (ii)
      reconstruction of optical laboratory 2, (iii) construction of a visible
      synchrotron radiation beam extraction mirror made of beryllium, (iv) small-beam
      profile measurement by means of the image restoration method, (v) application of
      the adaptive optical system for correction of distorted wavefronts caused by
      deformation of the extraction mirror, (vi) construction of a synchrotron
      radiation interferometer for investigation of the spatial coherency of the
      visible synchrotron radiation beam and its application to the measurement of
      vertical beam profile and size.

PMID- 15263672
TI  - Initial data from the 30-element ORTEC HPGe detector array and the XSPRESS pulse
      processing electronics at the SRS, Daresbury Laboratory.
AB  - Following the completion of the collaborative project between CLRC Daresbury
      Laboratory and EG&G ORTEC to develop the world's first 30-element HPGe detector
      for fluorescence XAFS, it has now been tested and commissioned at the SRS. The
      system was commissioned with the XSPRESS digital pulse-processing electronics and
      this has demonstrated processed count rates in excess of 10 MHz. Initial data
      have been recorded and are presented.

PMID- 15263673
TI  - Development of high-throughput flexible multichannel electron detectors at
      Daresbury Laboratory.
AB  - Continuing demands from Synchrotron Radiation Source (SRS) end-users for higher
      throughput and improved reliability in photoelectron spectroscopy experiments
      have driven an intensive development programme for new multichannel electron
      detectors. The development philosophy focuses on high throughput to match present
      and future source intensity, flexible structures to allow increased mobility of
      designs and modular design for easy maintenance and repair. Developments include
      parallel readout electronics and innovative detector heads for the hemispherical
      deflection analysers currently in use on the SRS. Novel anode arrays have been
      implemented in the detector heads and extensive microchannel plate (MCP)
      characterization has been undertaken to source the MCPs most suited to this
      application. The present multichannel detection systems provide a significant
      enhancement to single-channel detection systems. They have also surpassed
      previous multichannel detection systems due to their high throughput, flexible
      structure and modular design. Information on these developments and experimental
      results obtained at Daresbury Laboratory are presented.

PMID- 15263674
TI  - Dead-time correction of a multi-element SSD for fluorescent XAFS.
AB  - The correct evaluation of the live time of a detection system is found to be
      important for correcting the counting loss of a multi-element detection system
      for fluorescent XAFS experiments. Synchronous resetting of preamplifiers and the
      suspension of electronics during the reset period is an effective method. The
      dead time of the incoming count rate should also be corrected, since its non
      linearity cannot be neglected. A 19-element solid-state detector system which can
      count up to 3.7 x 10(5) counts s(-1) channel(-1) with <270 eV FWHM for Mn Kalpha
      has been realized; the dead time was independent of the incoming photon energy.

PMID- 15263675
TI  - A new image-plate reader for various sizes and shapes.
AB  - A new image-plate reader which can read image plates (IPs) having various sizes
      and shapes has been developed. The machine consists of a rotating laser head to
      induce luminescence photons from IPs and a porous cylindrical holder made of a
      composite of cast iron and porous ceramic - so-called 'breathnite'. Image plates
      can be fixed onto the inner surface of the cylindrical holder by evacuating the
      outer surface through a vacuum chamber with a mechanical pump. Image plates
      having various shapes and sizes up to 400 x 400 mm can be fixed without covering
      the open surface on the cylinder. In spite of such flexibility to various
      applications, the reader produces competitive performances compared with other
      commercial readers.

PMID- 15263676
TI  - X-ray polarimetry with the microstrip gas chamber.
AB  - A two-dimensional microstrip gas chamber (MSGC) with a 5 cm x 5 cm detection area
      has been developed. It has 254 anodes and 255 back strips, both with 200 micro m
      pitches. Using this MSGC, linear polarization of X-rays was successfully measured
      in the energy range 6-14 keV. In addition, the performance of the MSGC as an X
      ray imaging polarimeter has been simulated using the EGS4 program (Electron Gamma
      Shower, Version 4) modified for this purpose. In this article, the results of
      both the polarization measurement and the simulation are reported.

PMID- 15263677
TI  - A multiwire proportional counter for very high counting rates.
AB  - Preliminary measurements in a proportional counter with two independently
      counting wires showed that counting rates up to 10(6) counts s(-1) wire(-1) can
      be reached without critical loss in the 'true versus measured' linearity
      relation. Results obtained with a detector containing 30 active wires (2 mm
      pitch) are presented. With each wire is associated a fast pre-amplifier and a
      discriminator channel. Global counting rates in excess of 10(7) events s(-1) are
      reported. Dead-time losses are corrected by use of simple mathematical-modelling
      functions. Data-acquisition systems are described for one-dimensional (real-time)
      and two-dimensional (off-line) position-sensitive detection systems.

PMID- 15263678
TI  - Development of 32-channel silicon drift detectors and digital electronics for X
      ray spectroscopy.
AB  - The performance of silicon-drift-detector (SDD) arrays and digital electronics
      designed for X-ray absorption spectroscopy in the fluorescence excitation mode is
      reported. Different detectors have been manufactured and tested: two single
      channel SDDs with different active areas (10 mm(2) and 1 cm(2)) and a monolithic
      2 cm(2) SDD with eight readout anodes. The energy resolution varies between 160
      and 170 eV FWHM. A new digital multichannel shaping amplifier has been produced.
      Its performance is presented in comparison with that of a standard commercial
      shaper.

PMID- 15263679
TI  - High-accuracy detector calibration in the 3-1500 eV spectral range at the PTB
      radiometry laboratory.
AB  - State-of-the-art detector calibration in the UV/VUV and soft X-ray spectral
      ranges at the Physikalisch-Technische Bundesanstalt (PTB) is based on the primary
      detector standard SYRES, a cryogenic electrical substitution radiometer capable
      of measuring radiant power of a few micro W. At the PTB radiometry laboratory at
      the synchrotron radiation facility BESSY, two dedicated beamlines are operated,
      providing monochromatic radiation of high spectral purity, high radiant power and
      tunable photon energy in the 3-1500 eV range. The spectral responsivity of
      detectors, e.g. photodiodes, can be measured with a relative uncertainty of about
      1% by direct comparison with SYRES, as will be demonstrated for PtSi/Si and
      GaAsP/Au Schottky and silicon n-on-p photodiodes. The calibration of photon
      counting detectors traceable to SYRES can by accomplished by exploiting the
      unique capability to scale the spectral photon flux over several orders of
      magnitude by changing the stored electron current. Calibrations of CCDs and
      photomultipliers are presented as examples.

PMID- 15263680
TI  - Absolute soft X-ray measurements using an ion chamber.
AB  - Measurements of soft X-ray absolute intensities have been carried out using a
      double ion chamber and monochromated synchrotron radiation. The chamber is
      cylindrical and 1.3 m long. The soft X-ray beam enters the chamber at a position
      off the central axis, and the produced ions are collected with electrodes on the
      opposite side to the photon entrance. An index constant for rare gas, the gamma
      value, which is the average number of electrons emitted from an atom having
      absorbed a photon, was used for obtaining the absolute photon intensity. The
      obtained intensity ranges from 1 Gphotons s(-1) to 25 Gphotons s(-1) in the
      energy range 72-800 eV. The estimated uncertainty is about 5-20% depending on the
      intensity and the spectral purity of the soft X-rays.

PMID- 15263681
TI  - A new ion chamber with a movable photodiode monitor for absolute intensity
      measurements of soft X-rays.
AB  - A new ion-chamber system with a movable monitor detector for the measurement of
      soft X-ray absolute intensity is introduced. The calibration results are also
      given.

PMID- 15263682
TI  - New methods for semiconductor charge-diffusion-length measurements using
      synchrotron radiation.
AB  - The extension of a new theory on the X-ray energy response of semiconductor
      detectors is carried out to characterize the X-ray response of a multichannel
      semiconductor detector fabricated on one silicon wafer. Recently, these
      multichannel detectors have been widely utilized for position-sensitive
      observations in various research fields, including synchrotron radiation research
      and fusion-plasma investigations. This article represents the verification of the
      physics essentials of a proposed theory on the X-ray response of semiconductor
      detectors. The three-dimensional charge-diffusion effects on the adjoining
      detector-channel signals are experimentally demonstrated at the Photon Factory
      for two types of multichannel detectors. These findings are conveniently
      applicable for measuring diffusion lengths for industrial requirements.

PMID- 15263683
TI  - Characterization and interpretation of the quantum efficiencies of multilayer
      semiconductor detectors using a new theory.
AB  - On the basis of a new theory of semiconductor X-ray detector response, a new type
      of multilayer semiconductor detector was designed and developed for convenient
      energy analyses of intense incident X-ray flux in a cumulative-current mode.
      Another anticipated useful property of the developed detector is a drastic
      improvement in high-energy X-ray response ranging over several hundred eV. The
      formula for the quantum efficiency of multilayer semiconductor detectors and its
      physical interpretations are proposed and have been successfully verified by
      synchrotron radiation experiments at the Photon Factory. These detectors are
      useful for data analyses under strong radiation-field conditions, including
      fusion-plasma-emitting X-rays and energetic heavy-particle beams, without the use
      of high-bias applications.

PMID- 15263684
TI  - Detailed simulation of the response function of an Si(Li) detector.
AB  - The response function of an Si(Li) detector was calculated by using a Monte Carlo
      method for photon energies below 10 keV. In the simulation, electron elastic
      scattering cross sections calculated using the partial-wave expansion method were
      used instead of the Born approximation to simulate the electron scattering more
      accurately. The carrier collection probability near the gold-silicon interface
      was derived by solving the carrier continuity equation with drift, diffusion and
      surface recombination by a finite recombination velocity. For two detectors, good
      agreement was found for low-energy tailing between measured and simulated
      response functions. The integrated detection efficiency is almost identical with
      the transmittance in the front gold electrode showing a maximum difference of 2%
      at the Au M(4)-absorption edge.

PMID- 15263685
TI  - Pulse-height measurements with a cooled avalanche-photodiode detector.
AB  - A cooled avalanche-photodiode (APD) detector has been developed for X-ray
      diffraction experiments. Although an APD is normally used at room temperature and
      a high internal gain, the energy resolution can be improved by decreasing
      temperature and gain. The APD device was cooled to 253 K by a thermoelectric
      cooler. When the gain was M = 13, the energy resolution was 5% (FWHM) at 16.53
      keV with a charge-sensitive preamplifier. By scanning the discriminator threshold
      level of a fast-counting system, energy spectra were obtained at M approximately
      50 and count rates of up to 4.7 x 10(7) s(-1).

PMID- 15263686
TI  - A compact UHV X-ray diffractometer for studying surfaces and interfaces.
AB  - A compact ultra-high-vacuum (UHV) X-ray diffractometer for surface glancing X-ray
      scattering has been constructed. All the equipment, including a rotating-anode
      source of 18 kW and a UHV specimen chamber, is arranged on one optical table of
      dimensions 70 x 90 cm. The specimen chamber is 14 cm in diameter and 20 cm high
      and can be evacuated up to 3 x 10(-8) Pa. It is equipped with two Be windows of
      thicknesses 0.2 and 0.4 mm. Specimen orientation in the vacuum is controlled from
      the outside. The specimen can be heated up to 773 K. The chamber has two
      evaporation cells and can be used for in situ observations of growing crystal
      surfaces. Using this instrument, we observed a mechanically polished Ag surface
      and successfully made an in situ observation of the layer-by-layer growth of a
      PbSe(111) surface. The instrument will be useful for preliminary experiments
      using laboratory sources, prior to final measurements at synchrotron radiation
      facilities.

PMID- 15263687
TI  - An ultrahigh-vacuum chamber for surface X-ray diffraction.
AB  - An ultrahigh-vacuum environmental chamber for surface X-ray diffraction on
      Station 9.4 at the Synchrotron Radiation Source, Daresbury Laboratory, is
      described. Film growth can be monitored by simultaneously recording the Auger
      signal and the X-ray intensity at a particular point in reciprocal space. Such in
      situ measurements are essential for understanding the dynamic processes that
      occur during adsorption. An example is given in which the specularly reflected X
      ray signal is correlated with Auger plots, during growth of Tl on Cu(001). In
      addition, the diffractometer and chamber combination allow large reconstructions
      to be investigated as shown by the in-plane structural analysis of the c(4x4)
      InSb surface. A study of the layer structure of Cr on Ag(001), in which an
      extended out-of-plane detector assembly was used, is also presented.

PMID- 15263688
TI  - An additional axis for the surface X-ray diffractometer.
AB  - A new surface X-ray diffractometer based on a kappa-type diffractometer will be
      installed in BL14B1, SPring-8. This diffractometer has an additional axis on its
      detector arm for rotating the receiving slit about the normal of the slit plane,
      in addition to two axes for positioning the detector. This additional axis is
      founded on the consideration of the correction factor which has been derived so
      as to be valid for the z-axis mode measurement using any incoming and outgoing
      angles of the X-ray beam. The rotational slit allows accurate measurement of the
      surface structure factor up to large perpendicular momentum transfer.

PMID- 15263689
TI  - Surface X-ray scattering system at the SRRC.
AB  - A UHV surface X-ray scattering system has been constructed at the SRRC, providing
      users with a state-of-the-art system for performing X-ray scattering studies of
      two-dimensional crystallography, in situ growth mechanisms as well as phase
      transitions of surfaces and interfaces. A study of the phase transition of the
      Si(001) reconstructed surface was conducted to commission both the scattering
      system and the SRRC X-ray beamline. The detailed design and performance of the
      SRRC surface X-ray scattering system together with the results of the Si(001)
      study are presented.

PMID- 15263690
TI  - Observation of composition in surface monolayers by X-ray scattering spectra
      caused by crystal truncation and interferences.
AB  - X-ray crystal-truncation-rod (CTR) scattering measurements using synchrotron
      radiation and an imaging plate can reveal the composition of a surface monolayer.
      Even when the composition is changed in only one atomic layer on the top surface,
      the X-ray CTR spectrum can change due to the differences in composition. X-ray
      CTR spectra are greatly enhanced by X-ray interference when a sample is designed
      properly. In this paper, it is shown by theoretical calculations and experiments
      for AlAs/GaAs samples grown by MBE that a 1 ML (monolayer)-thick AlAs layer
      embedded under 10 ML below the surface can enhance the modulation of an X-ray CTR
      spectrum.

PMID- 15263691
TI  - Micro X-ray diffraction analysis of thin films using grazing-exit conditions.
AB  - An X-ray diffraction technique using a hard X-ray microbeam for thin-film
      analysis has been developed. To optimize the spatial resolution and the surface
      sensitivity, the X-ray microbeam strikes the sample surface at a large glancing
      angle while the diffracted X-ray signal is detected with a small (grazing) exit
      angle. Kirkpatrick-Baez optics developed at the Photon Factory were used, in
      combination with a multilayer monochromator, for focusing X-rays. The focused
      beam size was about 10 x 10 micro m. X-ray diffraction patterns of Pd, Pt and
      their layered structure were measured. Using a small exit angle, the signal-to
      background ratio was improved due to a shallow escape depth. Under the grazing
      exit condition, the refraction effect of diffracted X-rays was observed,
      indicating the possibility of surface sensitivity.

PMID- 15263692
TI  - Development of a compact six-circle goniometer.
AB  - A compact versatile six-axis goniometer has been built which can be used with the
      scattering plane vertical or horizontal for anomalous X-ray diffraction and
      diffraction X-ray absorption fine structure using a tunable X-ray undulator at
      SPring-8. The diffractometer consists of a four-circle goniometer for the
      standard omega, 2theta, phi and chi motions and a two-circle goniometer on the
      2theta arm for mounting the detector and analyser crystal. The goniometer is
      controlled via Ethernet, and standard data-acquisition software with a graphical
      user interface has been developed. A closed-cycle helium cryostat is mounted on
      the omega axis for temperature-dependent experiments from 330 K to 14 K.
      Preliminary experiments on a Bi(2)Sr(2)CaCu(2)O(8) single crystal demonstrate the
      performance. Superstructure peaks due to the one-dimensional spatial modulations
      in the b axis were recorded as a function of temperature above 20 K using an
      image plate.

PMID- 15263693
TI  - DAFS measurements using the image-plate Weissenberg method.
AB  - An instrumental technique for DAFS measurements which can provide site-specific
      information is proposed. The approach uses (i) focusing optics with parabolic
      mirrors and a double-crystal monochromator, (ii) the Laue and Bragg settings and
      (iii) data collection by the image-plate Weissenberg method. Six image exposures
      are recorded per plate at five intrinsic energies and one reference energy. The
      single-crystal measurements were performed at the Co K-absorption edge, and the
      200, 220 and 311 reflections of CoO and 511 and 911 reflections of Co(3)O(4) were
      used for analysis. The regression analysis of chi(k), Fourier transforms of
      k(3)chi(k) and back-Fourier filtering have been performed.

PMID- 15263694
TI  - Sample-angle feedback for diffraction anomalous fine-structure spectroscopy.
AB  - Diffraction anomalous fine-structure (DAFS) experiments measure Bragg peak
      intensities as continuous functions of photon energy near a core-level
      excitation. Measuring the integrated intensity at each energy makes the
      experiments prohibitively slow; however, in many cases DAFS can be collected
      quickly by measuring only the peak intensity at the center of the rocking curve.
      A piezoelectric-actuator-driven stage has been designed and tested as part of a
      sample-angle feedback circuit for locking onto the maximum of the rocking curve
      while the energy is scanned. Although software peak-tracking requires only a
      simple calculation of diffractometer angles, it is found that the additional
      hardware feedback dramatically improves the reproducibility of the data.

PMID- 15263695
TI  - A new macromolecular oscillation camera at CHESS.
AB  - Increasing X-ray flux and decreasing crystal size are two factors placing new
      demands on macromolecular diffraction cameras at synchrotrons. A new oscillation
      camera with high mechanical precision and fast rotation speed is described.

PMID- 15263696
TI  - Four-crystal camera at BSRF and its applications.
AB  - The four-crystal camera is one of the major items of equipment of the topography
      station at the Beijing Synchrotron Radiation Facility. The design and some
      applications of this camera are presented.

PMID- 15263697
TI  - Valence-difference contrast measurements utilizing X-ray anomalous scattering.
AB  - Anomalous scattering experiments with X-ray wavelengths close to an absorption
      edge have made it possible to determine independently the behaviour of ions in
      different valence states. The anomalous scattering factors of Fe(2+) and Fe(3+)
      obtained from both absorption and diffraction data have a large difference in f'
      between the two kinds of ions. Using a valence-difference contrast method, Bragg
      and diffuse scattering measurements were carried out for single crystals of
      Fe(3)O(4) at low temperatures. The results demonstrate the ability of the
      contrast method to resolve charge ordering and valence fluctuation details.

PMID- 15263698
TI  - Partial structural functions of binary liquids estimated from anomalous X-ray
      scattering measurements.
AB  - A new apparatus has been built for structural studies of high-temperature liquids
      using the anomalous X-ray scattering (AXS) method with synchrotron radiation. AXS
      measurements were made in the asymmetrical reflection mode for a free liquid
      surface by changing the beam direction using an additional mirror system. The
      usefulness and capabilities of this new equipment were confirmed by obtaining the
      individual partial structural functions of liquid Bi(30)Ga(70) alloy.

PMID- 15263699
TI  - Multiple-wavelength powder diffraction using imaging plates at the Australian
      National Beamline.
AB  - The Australian powder diffractometer at the Photon Factory is capable of
      recording multiple powder-diffraction scans in less than 5 min per pattern using
      imaging plates in Debye-Scherrer geometry. This, coupled with incrementing the X
      ray beam energy in suitably small steps (down to approximately 2 eV) between
      exposures, allows fast collection of anomalous diffraction data. Data collected
      from a copper oxide-based superconductor at energies near the Cu K-absorption
      edge are presented, along with an account of the technique used to extract
      multiple-exposure powder-diffraction data from imaging plates.

PMID- 15263700
TI  - New high- and low-temperature apparatus for synchrotron polycrystalline X-ray
      diffraction.
AB  - A high-temperature furnace with an induction heater coil and a cryogenic system
      based on closed-cycle refrigeration have been assembled to enhance the non
      ambient powder diffraction facilities at the Synchrotron Radiation Source,
      Daresbury Laboratory. The commissioning of the high- and low-temperature devices
      on the high-resolution powder diffractometer of Station 2.3 is described. The
      combined temperature range provided by the furnace/cryostat is 10-1500 K. Results
      from Fe and NH(4)Br powder samples are presented to demonstrate the operation of
      the apparatus. The developments presented in this paper are applicable to a wide
      range of other experiments and diffraction geometries.

PMID- 15263701
TI  - High-pressure system for Compton scattering experiments.
AB  - High-pressure apparatus for Compton scattering experiments has been developed to
      study the momentum distribution of conduction electrons in metals and alloys at
      high pressure. This apparatus was applied to observe the Compton profile of
      metallic Li under pressure. It was found that the Compton profile at high
      pressure could be obtained within several hours by using this apparatus and
      synchrotron radiation. The result on the pressure dependence of the Fermi
      momentum of Li obtained here is in good agreement with that predicted from the
      free-electron model.

PMID- 15263702
TI  - Development of an in-situ X-ray diffraction system for observation of
      electrodeposition of metallic layers.
AB  - In order to study the dynamic phenomena of electrodeposition of metallic layers,
      an in situ X-ray diffraction system has been newly developed using an
      electrochemical cell and an image-plate detector. Electrodeposition of Zn on an
      Fe(100) single-crystal surface with a current density at 0.5 A cm(-2) was
      demonstrated in this study. Time-resolved diffraction patterns were obtained by
      scanning the image plate. It was found that Zn(101) layers were mainly formed
      from the initial stage of deposition and grew continuously on this substrate.
      Growth of other layers, such as Zn(103), Zn(110) and Zn(102), were also detected.
      On the other hand, Zn(100) and Zn(002) were not observed under this condition.

PMID- 15263703
TI  - A 3 T superconducting magnet for long-run magnetic Compton-scattering
      experiments.
AB  - A 3 T superconducting magnet has been designed and constructed for magnetic
      Compton-profile (MCP) measurements with the new capabilities that the magnetic
      field direction can be altered quickly (within 5 s) and liquid-He refill is not
      required for more than one week. For the latter capability, two refrigerators
      have been directly attached to the cryostat to maintain the low temperature of
      the radiation shields and for the recondensation of liquid He. The system has
      been satisfactorily operated for over one week.

PMID- 15263704
TI  - High-energy magnetic Compton scattering experiments at ESRF.
AB  - Investigations of spin densities in ferromagnetic materials using magnetic
      Compton scattering are reported. At the high-energy beamline ID15 at the ESRF,
      experiments have been carried out utilizing the high flux at very high photon
      energies. Energies from 60 up to 1000 keV have been used for investigations of
      experimental resolution, cross section, spin moments and momentum distribution.
      Optimized conditions are found for photon energies from 200 to 250 keV with a
      momentum resolution < 0.4 a.u. and a doubled magnetic effect compared with
      earlier measurements. In the determination of absolute spin moments multiple
      scattering has to be taken into account.

PMID- 15263705
TI  - The influence of interface roughness on Mossbauer filtration of synchrotron
      radiation at an isotope interface.
AB  - The influence of interface irregularities on synchrotron radiation Mossbauer
      filtration at an isotope interface is examined theoretically. Calculations are
      performed for a random-roughness interface model for a (56)Fe/(57)Fe isotope
      interface. The analysis shows that, despite a drop in the efficiency in the real
      structures compared with the idealized structures, the efficiency of Mossbauer
      filtration of synchrotron radiation remains high enough to ensure a successful
      experiment. In particular it was found that, as well as a regular saw-like
      profile of the external interface, a randomly rough profile of the external
      interface may also be used in the Mossbauer filtration experiment if the
      roughness parameters satisfy certain demands.

PMID- 15263706
TI  - Mossbauer surface-guided waves in media with space modulation of Mossbauer
      isotope concentration.
AB  - Rapid progress in Mossbauer spectroscopy combined with synchrotron radiation (SR)
      makes it urgent to study the interaction of SR with structures which have a space
      modulation of the Mossbauer isotope concentration, and thereby to reveal new
      effects in this interaction. Presented here are theoretical studies of the
      Mossbauer surface-guided mode (MSGM) in such media. MSGMs are analogous to the
      well known surface-guided electromagnetic waves (SGEW) in periodic media.
      However, because of their resonant interaction with Mossbauer nuclei they reveal
      some qualitative peculiarities compared with the case of conventional SGEW. The
      MSGMs for the case of purely nuclear Bragg scattering of quanta at a plane
      interface between a homogeneous medium and a medium with a periodic space
      modulation of the Mossbauer isotope concentration are investigated theoretically.
      The conditions of MSGM existence and allowed spectral intervals for the MSGM and
      their dependence on the period of space modulation and the degree of medium
      enrichment by the Mossbauer isotope are found. It is shown that the allowed
      interval of the MSGM frequencies is located at one side relative to the exact
      Mossbauer resonant frequency. Its width is of the order of the Mossbauer line
      width and can be effectively changed by the variation of the modulation period or
      the Mossbauer isotope concentration. For the MSGM frequencies close to the
      boundary of the MSGM existence interval, the attenuation of an MSGM propagating
      along the interface may be essentially lower than the conventional Mossbauer
      radiation attenuation in the same medium. The possibilities of SR Mossbauer
      filtration by means of MSGM are briefly discussed.

PMID- 15263707
TI  - A high-temperature environmental chamber for nuclear-resonant Bragg scattering
      studies.
AB  - A compact environmental chamber with a furnace operating in the range from room
      temperature to about 900 K has been built for a high-temperature nuclear-resonant
      Bragg scattering study. The compact size (75 mm diameter and 70 mm depth) allows
      an external magnetic field to be applied from outside permanent Nd-Fe-B alloy
      magnets; a magnetic field up to 1000 G has been obtained. The chamber can be
      mounted on a precise theta-2theta goniometer so that in situ observations of X
      ray diffraction from a single crystal can be carried out. The temperature is
      measured by two thermocouples placed at the top and back of the sample and
      controlled by a PID controller. The temperature fluctuation of the chamber is
      less than +/-1 K.

PMID- 15263708
TI  - X-ray characterization of alpha-Fe(2)O(3) single crystals containing 2.2% and 95%
      (57)Fe.
AB  - alpha-Fe(2)O(3) single crystals containing 2.2% and 95% (57)Fe isotopes were
      characterized by means of X-ray topography, the diffraction rocking curve and the
      integrated intensity. These crystals were revealed to be nearly perfect and
      suitable for a further nuclear-resonant Bragg-scattering study.

PMID- 15263709
TI  - Precision goniometer equipped with a 22-bit absolute rotary encoder.
AB  - The calibration of a compact precision goniometer equipped with a 22-bit absolute
      rotary encoder is presented. The goniometer is a modified Huber 410 goniometer:
      the diffraction angles can be coarsely generated by a stepping-motor-driven worm
      gear and precisely interpolated by a piezoactuator-driven tangent arm. The
      angular accuracy of the precision rotary stage was evaluated with an
      autocollimator. It was shown that the deviation from circularity of the rolling
      bearing utilized in the precision rotary stage restricts the angular positioning
      accuracy of the goniometer, and results in an angular accuracy ten times larger
      than the angular resolution of 0.01 arcsec. The 22-bit encoder was calibrated by
      an incremental rotary encoder. It became evident that the accuracy of the
      absolute encoder is approximately 18 bit due to systematic errors.

PMID- 15263710
TI  - Tensometry of carbon fibres and elastomers at the diffractometer at BL20B of the
      Photon Factory.
AB  - Two systems have been developed for the simultaneous recording of the SAXS and
      the WAXS patterns from carbon fibre and elastomer samples which are placed under
      stress. The systems have been designed to fit inside the versatile vacuum
      diffractometer (BIGDIFF) at the Photon Factory. In one system, use is made of the
      ability to move the imaging-plate cassette. In the other, use has been made of an
      imaging-plate changer which can deliver up to 13 plates into position with a duty
      cycle of about 60 s. In this case each imaging plate can record SAXS/WAXS
      patterns in the range 0.5-20 degrees due to the passage of the beam through the
      specimen which is mounted in a specially designed tensometer. Because BIGDIFF is
      a vacuum diffractometer and parasitic scattering is small, exposure times as
      short as 2 s can give acceptable SAXS/WAXS patterns. The systems have been used
      for the study of both the change of structure with strain, and the relaxation
      processes which occur as a result of the sample being strained at a fixed rate by
      a predetermined amount.

PMID- 15263711
TI  - Structure changes in the sol-gel systems of hydrated oxides.
AB  - This work was undertaken partly with financial support of the RBRF of the
      Ministry of Science of the Russian Government (N95-03-09682a) and partly with
      financial support of the Ministry of Education, Science, Sports and Culture
      (MONBUSHO) of the Government of Japan.Sols of hydrated aluminium oxide, hydrated
      zirconium oxide and their mixtures were investigated during the xerogel-amorphous
      product-crystalline-product transition by SAXS using synchrotron radiation. In
      the different temperature regions certain changes in structure and morphology
      were observed. Some correlation between the characteristics of the initial sols
      and their mixtures (the size and shape of the pores) was observed. In the
      temperature region 298-1173 K the characteristics of the mixed sol are defined by
      the characteristics of the initial sols.

PMID- 15263712
TI  - Observation of the strain field near the Si(111) 7 x 7 surface with a new X-ray
      diffraction technique.
AB  - A new X-ray diffraction technique has been developed in order to measure the
      strain field near a solid surface under ultrahigh vacuum (UHV) conditions. The X
      ray optics use an extremely asymmetric Bragg-case bulk reflection. The glancing
      angle of the X-rays can be set near the critical angle of total reflection by
      tuning the X-ray energy. Using this technique, rocking curves for Si surfaces
      with different surface structures, i.e. a native oxide surface, a slightly oxide
      surface and an Si(111) 7 x 7 surface, were measured. It was found that the widths
      of the rocking curves depend on the surface structures. This technique is
      efficient in distinguishing the strain field corresponding to each surface
      structure.

PMID- 15263713
TI  - Investigation of the phase shift in X-ray forward diffraction using an X-ray
      interferometer.
AB  - The phase shift of forward-diffracted X-rays by a perfect crystal is discussed on
      the basis of the dynamical theory of X-ray diffraction. By means of a triple Laue
      case X-ray interferometer, the phase shift of forward-diffracted X-rays by a
      silicon crystal in the Bragg geometry was investigated.

PMID- 15263714
TI  - Layered structure analysis of GMR multilayers by X-ray reflectometry using the
      anomalous dispersion effect.
AB  - As a basic layered structure for giant magnetoresistive (GMR) heads,
      NiFe/Cu/NiFe/Ta/Si substrate was measured by X-ray reflectometry at Cu Kalpha, Cu
      Kbeta and Cu K-absorption-edge energies. The accuracy of both the Cu thickness
      and the interface width between the upper NiFe and the Cu layers was found to
      improve in the order Cu Kalpha < Cu Kbeta < Cu K-edge. The final thickness and
      interface width values obtained from Cu Kbeta reflectivity are in good agreement
      with those from the Cu K-edge. The anomalous-dispersion effect is useful in the
      more accurate analysis of the layered structure of transition metal multilayers
      because it causes a large difference in the refractive indices of specific
      elements near the absorption edge. The Kbeta X-rays, which can be produced from
      conventional X-ray sources, are also available for the accurate analysis of
      reflectivity measurements.

PMID- 15263715
TI  - Site specification on normal and magnetic XANES of ferrimagnetic Fe(3)O(4) by
      means of resonant magnetic Bragg scattering.
AB  - Resonant magnetic Bragg scattering (RMBS) for several reflections has been
      measured at the Fe K-edge in Fe(3)O(4). The normal and magnetic X-ray absorption
      near-edge structure (XANES) for two types of Fe ion site (tetrahedral and
      octahedral) were successfully determined from the analysis of DAFS and RMBS
      spectra on the assumption that there was an electric dipole transition. The
      obtained normal XANES for the octahedral site is well explained as a mixture of
      Fe(2+) and Fe(3+) ions, and the characteristic feature of the magnetic XANES at
      the pre-edge peak is mainly contributed from the Fe(3+) ion at the tetrahedral
      site.

PMID- 15263716
TI  - Application of a fine thread beam to the structure analysis of a hemihedrally
      twinned crystal of hydroxylamine oxidoreductase.
AB  - Accurate diffraction intensity data have been collected from a twinned P6(3)
      crystal of the 24-haem protein hydroxylamine oxidoreductase, from a nitrifying
      chemoautotrophic bacterium Nitrosomonas europaea, using synchrotron radiation at
      station BL6A of the Photon Factory. Estimation of the twinning fraction and
      deconvoluted intensity data, including native and heavy-atom derivative data,
      gave an improved Patterson function. Four diffraction data sets were collected
      from one crystal and an estimation of the twinning fraction to confirm the
      phenomena was undertaken. The successfully detwinned data sets were utilized in
      the structure analysis of the present enzyme. The mechanism of twinned-crystal
      formation is also discussed.

PMID- 15263717
TI  - Structural studies of endohedral metallofullerenes by synchrotron radiation
      powder diffraction.
AB  - The endohedral natures of the metallofullerenes Y@C(82) and Sc(2)@C(8)4 are
      described based on synchrotron radiation powder diffraction experiments. For
      structural analysis, a combination of the maximum-entropy method (MEM) and
      Rietveld refinement was employed to analyse the complicated powder pattern. The
      obtained MEM charge densities show a clear distinction of the endohedral natures
      of the mono- and dimetallofullerenes.

PMID- 15263718
TI  - X-ray parametric scattering by a diamond crystal.
AB  - Spontaneous X-ray parametric scattering from a diamond single crystal has been
      observed at the Photon Factory. The high perfection of the diamond single crystal
      and the small angular divergence of synchrotron radiation has enabled down
      converted X-ray photon pairs to scatter into two small solid angles which satisfy
      the phase-matching condition. High-efficiency noise reduction was performed using
      avalanche photodiode detectors with good time resolution.

PMID- 15263719
TI  - In situ observation of phase transformation in an Fe-Zn system at high
      temperatures using an image plate.
AB  - A unique system has been developed for in situ observation of phase
      transformation at high temperatures. Changes in powder-diffraction patterns from
      a heated specimen can be measured continuously by scanning an image plate located
      behind a slit. A heating system has been designed for a sheet specimen (
      approximately 5 x 6 mm) using Joule heating, and it can heat the specimen up to
      1100 K at a rate of up to 160 K s(-1), where effects of thermal expansion are
      minimized by a mechanism releasing stress. This system was applied to Zn-coated (
      approximately 8 micro m in thickness) steel. At temperatures higher than the
      melting point of Zn, different types of Fe-Zn intermetallics formed sequentially
      through rapid interdiffusion. Changes in phase and crystallographic structure
      were monitored with a time resolution of less than a few seconds. It has been
      found that an addition of a small amount of an element, such as P, into Fe
      changes the incubation time before the alloying reaction starts. This system has
      been shown to have the potential for application to in situ observation of other
      reactions at high temperatures.

PMID- 15263720
TI  - On a spatially resolving USAXS instrument for operation at a third-generation
      synchrotron radiation source.
AB  - A point-collimation USAXS system based on the Bonse-Hart-diffractometer concept
      is proposed which takes advantage of a CCD detector to rapidly obtain two
      dimensional SAXS data at both high spatial and angular resolution for a line of
      points on the sample. The method might typically be employed using Bonse-Hart
      crystal optics in the horizontal plane, encompassing the high-angular-resolution
      scan direction, and a condensing monochromator in the out-of-diffraction-plane
      direction as the basis for a pinhole SAXS camera in that plane. The new system is
      well suited to operation at an undulator beamline on a third-generation
      synchrotron radiation source. Other applications of the instrument include (i)
      both absorption and phase-contrast imaging/tomography, (ii) polycrystalline
      topography, (iii) high-resolution triple-crystal measurements and (iv) diffuse
      scattering measurements.

PMID- 15263721
TI  - XAFS and X-MCD spectroscopies with undulator gap scan.
AB  - The first experimental applications of the undulator gap-scan technique in X-ray
      absorption spectroscopy are reported. The key advantage of this method is that
      during EXAFS scans the undulator is permanently tuned to the maximum of its
      emission peak in order to maximize the photon statistics. In X-MCD or spin
      polarized EXAFS studies with a helical undulator of the Helios type, the
      polarization rate can also be kept almost constant over a wide energy range.

PMID- 15263722
TI  - Two recent developments in XMCD.
AB  - This paper reports on two new technical developments concerning sample
      environments for X-ray magnetic circular dichroism (XMCD). The first measurements
      under high pressures of up to 30 GPa are described. The difficulties of combining
      the techniques of high pressure and XMCD are commented on. The second development
      involves the use of a fast-switching magnetic field. A new superconducting device
      is used to perform XMCD measurements on paramagnetic compounds in magnetic fields
      of up to 6 T. The small amplitude of the XMCD signal imposes, for a given signal
      to-noise ratio, a noise less than a few 10(-5). The signal-to-noise ratio is
      improved by the use of a series of acquisitions, switching the magnetic field
      between each acquisition. A very fast switching mechanism has been built based on
      mechanical rotation of a superconducting coil, with the sample kept in place
      inside the coil. The XMCD signals at the L(II,III)-edges of paramagnetic rare
      earth compounds have been measured at 4.5 K in fields of up to 6 T with a
      switching time of 11 s.

PMID- 15263723
TI  - X-ray linear birefringence and linear dichroism in a cobalt crystal measured with
      a tunable X-ray polarimeter.
AB  - X-ray linear birefringence and linear dichroism spectra have been measured
      simultaneously and quantitatively for the first time. The sample was a hexagonal
      cobalt single-crystal foil. The apparatus used was an energy-tunable X-ray
      polarimeter, consisting of a polarizer, a phase retarder and an analyser. The X
      ray energy was scanned over a range of 350 eV near the K-absorption edge. The
      Kramers-Kronig relation between the refraction and absorption anisotropy has been
      confirmed on an absolute scale. The phase-difference sensitivity of the
      polarimeter as a polarization inferometer is as small as 2pi/10000, which is
      about 100 times smaller than that of the Bonse-Hart inferometer.

PMID- 15263724
TI  - X-ray magnetic reflectometry using circularly polarized radiation.
AB  - Magnetic reflectometry experiments have been performed in the X-ray range at the
      L(2,3) edges of rhodium. What makes these experiments original is the insertion
      of a very compact double-bounce reflectometer upstream of the monochromator. This
      configuration makes full use of the high polarization rate of the helical
      undulator source. This advantage is reflected in the high quality of the data
      obtained after only a few accumulations. It is also shown that, by properly
      selecting the angle of incidence, one may obtain experimental differential X-ray
      reflectivity spectra dominated either by the dispersion or the absorption terms.

PMID- 15263725
TI  - Pump and probe X-ray absorption fine structure using high-brilliance photon
      sources.
AB  - Pump and probe X-ray absorption fine structure (XAFS) is used as a local probe of
      excited atoms, which can provide direct information on lattice distortion,
      relaxation and atomic rearrangements associated with electronic excitations. In
      situ XAFS experiments during optical excitation are reported. Utilizing a grazing
      incidence fluorescence excitation, which minimizes the mismatch between the
      probing depths of X-ray excitation and optical pumping, it is found that the
      dominant photoinduced defect state in amorphous selenium at low temperature is a
      pair of threefold neutral $C^0_3$ states: $2C^*_2 ?rightarrow (C^0_3-C^0_3)$,
      where $C^*_2$ denotes the twofold excited lone-pair state. The results indicate
      that optical pumping of chalcogen atoms at low temperature leads to locally over
      coordinated defect pairs similar to those in the liquid state. The origin of
      reversible photostructural changes, such as photodarkening or photoinduced
      fluidity, is attributed to the structural disorder caused by the formation and
      annihilation of dynamical interchain bonds during optical melting.

PMID- 15263726
TI  - X-ray absorption of bromonaphthalene dissolved in supercritical fluid xenon.
AB  - The results of Br K-edge X-ray absorption measurements of 1-bromonaphthalene
      dissolved in supercritical fluid Xe are reported. As the pressure of Xe confined
      in a high-pressure cell is increased, the absorption spectrum of bromonaphthalene
      gradually appears, showing that Xe in the supercritical fluid state solvates the
      bromonaphthalene molecule. The spectrum of the dissolved sample shows a
      remarkable difference from that of the pure liquid sample in the near-edge region
      of the X-ray absorption spectrum, reflecting the interaction of the solute
      material with solvent Xe. Ab initio full multiple-scattering calculations can
      reproduce the spectral features qualitatively. A large value of the Debye-Waller
      factor must be introduced to give the best fit, corresponding to a large degree
      of spatial disorder and violent thermal vibration of the Xe atoms around the Br
      atom.

PMID- 15263727
TI  - XAFS in the high-energy region.
AB  - XAFS (X-ray absorption fine-structure) spectra were measured near K-absorption
      edges of Ce (40.5 keV), Dy (53.8 keV), Ta (67.4 keV) and Pt (78.4 keV). The blunt
      K-edge jump due to the finite lifetime of the core hole was observed. This makes
      it difficult to extract EXAFS (extended X-ray absorption fine-structure)
      functions at low k values. Local structure parameters can be evaluated from the
      EXAFS spectra above K-absorption edges in the high-energy region as well as from
      those above L(III)-edges. It was found that the finite-lifetime effect of the
      core hole is effectively taken into the photoelectron mean-free-path term, as
      predicted theoretically.

PMID- 15263729
TI  - Spectrometer for polarized soft X-ray Raman scattering.
AB  - An experimental system for polarized soft X-ray Raman scattering spectroscopy has
      been constructed. The soft X-ray spectrometer is based on the Rowland circle
      geometry with a holographic spherical grating. Three types of gratings are used
      to cover the energy range from 18 eV to 1200 eV. According to a ray-trace
      simulation, the resolution is expected to be 200 meV at 700 eV by using a 10
      micro m slit width. The polarized and depolarized soft X-ray Raman scattering
      spectra can be measured by rotating the soft X-ray spectrometer around the axis
      of the incident beam. Preliminary measurements of polarized and depolarized
      spectra were accomplished at undulator beamline BL-2C of the Photon Factory.

PMID- 15263728
TI  - Polarization analysis in the 3-25 keV range at the ESRF magnetic scattering
      beamline.
AB  - The ESRF magnetic scattering beamline has been optimized for easy tunability of
      the polarization and energy in the 3-40 keV range. The linear horizontal
      polarization from the undulator reaches 99.9%, with a flux of approximately
      10(12) photons s(-1) at the sample. The diffractometer can operate in horizontal
      and vertical geometries, with an energy or polarization analyser. The
      capabilities of this beamline in terms of flux, energy tunability and
      polarization, permitted polarization analysis of resonant magnetic scattering
      from antiferromagnetic UPd(2)Si(2) at both the L(2)- and M(4)-edges of uranium,
      to separate the contributions of the 5f and 6d electrons to the magnetism.

PMID- 15263730
TI  - Phase transitions of CdS microcrystals under high pressure.
AB  - The experiment under high pressure using a diamond anvil cell (DAC) requires the
      utilization of synchrotron radiation. High-pressure experiments were performed
      using a DAC on CdS microcrystals, both in the far-IR and in the X-ray regions, in
      order to study the lattice dynamics and lattice stability concerned with the
      phase transitions. From these experiments, experimental evidence is presented
      indicating that a CdS microcrystal of smaller diameter shows a higher transition
      pressure for lattice transformation under pressure. The origin of such an
      increase in the transition pressure in the microcrystals is discussed in relation
      to the surface tension.

PMID- 15263731
TI  - Improvement of spectrometer energy resolution for high-resolution photoelectron
      spectroscopy.
AB  - For high-energy-resolution photoelectron spectroscopy using synchrotron
      radiation, the energy resolution of a commercial compact photoelectron
      spectrometer (hemispherical concentric spectrometer) was improved by reducing the
      size of the entrance and detector slits and optimizing the operation conditions
      of the lens voltage. Under the optimized conditions, ray-tracing simulations show
      that severe spectral intensity decreases can be avoided. An energy resolution of
      6.2 meV and a resolving power of 8100 at a kinetic energy of 50 eV were
      experimentally obtained.

PMID- 15263732
TI  - Density measurements of liquid under high pressure and high temperature.
AB  - A new method for density measurements by means of X-ray absorption under high
      pressure and high temperature using synchrotron radiation has been developed. The
      method has been modified for a large-volume Paris-Edinburgh press and combined
      with intense high-energy X-rays at the ESRF. In order to overcome effects of
      deformation of sample shape under pressure, a ruby cylinder was used as a sample
      container. The density was determined from the intensity profile of transmitted X
      rays. The densities of crystalline and liquid Bi were successfully measured up to
      750 K at 1 GPa.

PMID- 15263733
TI  - Real-time analysis for MBE by time-resolved core-level photoelectron
      spectroscopy.
AB  - A system has been developed for the real-time analysis of surface reactions
      during molecular beam epitaxial growth which uses photoelectron spectroscopy with
      VUV light taken from synchrotron radiation. This system consists of a synchrotron
      radiation beamline and growth/analysis apparatus in which photoelectron
      spectroscopy is performed with sub-second time resolution. In this system,
      photoelectron spectra are measured in sequence by a 'non-scanning' measurement
      method that enables the acquisition of snapshot photoelectron spectra using a
      multi-channel detector. This non-scanning measurement method was enabled by
      equipping an electric field correction grid. This system was used to monitor the
      photoelectron spectra of a GaSb(001) surface.

PMID- 15263734
TI  - An ultrahigh-vacuum goniometer for in situ soft X-ray standing-wave analysis of
      semiconductor surfaces.
AB  - An ultrahigh-vacuum goniometer was developed for in situ X-ray standing-wave
      (XSW) analysis of semiconductor surfaces prepared by molecular-beam epitaxy
      (MBE). Although two ultrahigh-vacuum motors for chi and phi rotating axes are
      inside the analysis chamber, low-energy photoelectrons can still be collected as
      the magnetic field is sufficiently suppressed by using metal shields.
      Furthermore, the sample can be annealed at temperatures higher than 870 K on the
      goniometer in the analysis chamber. This goniometer is used at beamline 1A (BL
      1A) at the Photon Factory, where both monochromated soft X-rays and UV radiation
      are available. This analysis system was shown to be suitable not only for in situ
      soft-XSW and X-ray absorption near-edge structure (XANES) studies but also for
      synchrotron radiation photoelectron spectroscopy (SRPES) studies. The annealing
      effects on an S-adsorbed GaAs(001) surface could be studied by SRPES, XANES and
      XSW using this new goniometer.

PMID- 15263735
TI  - Experimental comparison between the conversion electron yield and X-ray
      fluorescence in catalyst analysis.
AB  - To evaluate the application of the conversion-electron-yield (CEY) method in
      catalyst analysis, the intensities of the CEY and X-ray fluorescence (XRF) as a
      function of glancing angle were measured simultaneously. The probing depth of the
      CEY method is shallower than that of the XRF method. The CEY method also shows
      potential application for the analysis of even a powder specimen of a low
      concentration zeolite catalyst.

PMID- 15263736
TI  - Combined system of synchrotron radiation and laser for solid-state research.
AB  - Two combined systems of synchrotron radiation and laser have been constructed for
      solid-state research. One is a laser-induced fluorescence system to observe
      synchrotron radiation-induced desorption of alkali atoms from ionic crystals,
      which consists of a laser diode with a high repetition rate and synchrotron
      radiation under a single-bunch operation. The other is a system of two-photon
      spectroscopy, which is based on the combination of synchrotron radiation pulses
      with a low intensity and high repetition rate and Nd:YAG laser pulses with a high
      intensity and low repetition rate. The experimental systems and the preliminary
      results are presented in this report.

PMID- 15263737
TI  - A compact molecular-beam epitaxy apparatus for in situ soft X-ray magnetic
      circular dichroism experiments.
AB  - An economical and easily movable molecular-beam epitaxy (MBE) apparatus which
      prepares magnetic ultrathin films and superlattices with atomically well
      controlled interfaces has been designed and constructed. Cleaning and
      characterization of substrates, sample deposition in a layer-by-layer fashion,
      and characterization of samples both during and after growth can be carried out
      in a single ultrahigh vacuum (UHV) chamber. This MBE apparatus is combined with
      UHV high-field magneto-optical instruments for in situ soft X-ray magnetic
      circular dichroism experiments on two-dimensional magnetic systems.

PMID- 15263738
TI  - Photoionization studies of sulfur radicals and products of their reactions.
AB  - A discharge flow-photoionization mass spectrometric system coupled to a
      synchrotron is employed to study intermediates and products of sulfur radical
      reactions related to atmospheric chemistry. Sulfur radicals are generated from
      reactions of oxygen or chlorine atoms with sulfur compounds in a flow tube. The
      gaseous reaction products are sampled into the ionization region via a three
      stage differential pumping scheme. Photoionization spectra and ionization
      energies are measured by dispersing synchrotron radiation to ionize the samples.
      Using this technique, photoionization spectra and ionization energies of HSO,
      CH(3)SO, C(2)H(5)SO, HSCl, and some secondary reaction products, SSCl, HSSCl,
      HSSSH, CH(3)SOH and CH(3)SS(O)CH(3), were measured for the first time.

PMID- 15263739
TI  - Angle-resolved UV photoelectron spectra (UPS) of thin films of perylene-3,4,9,10
      tetracarboxylic dianhydride on MoS(2).
AB  - Angle-resolved UV photoelectron spectra (ARUPS) were measured for thin films of
      perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) deposited on cleaved MoS(2)
      surfaces. The take-off angle (theta) dependence of the photoelectron intensity of
      the highest pi band showed a sharp maximum at theta = 32-34 degrees. A spectral
      feature of the binding energy at approximately 8.9 eV, which is believed to
      originate from a pi state, showed a remarkably different theta dependence from
      that of the pi band. A quantitative analysis of the observed theta dependencies
      clearly indicates that (a) the feature at approximately 8.9 eV originates from
      the oxygen 2p non-bonding states and (b) the molecules lie flat on the substrate
      surface.

PMID- 15263740
TI  - Temperature dependence of photoelectron angular distribution from thin films of
      chloroaluminum phthalocyanine on MoS(2).
AB  - Angle-resolved UV photoelectron spectra were measured for thin films of
      chloroaluminum phthalocyanine deposited on cleaved MoS(2) surfaces. The take-off
      angle (theta) dependence of the photoelectron intensity of the highest pi band
      showed a remarkable sharpening upon cooling the film, indicating that thermal
      excitation of molecular vibrations gives a considerable broadening of the
      photoelectron angular distribution. The theta dependence observed at
      approximately 120 K agrees well with that calculated.

PMID- 15263741
TI  - In situ studies of metal-semiconductor interactions with synchrotron radiation.
AB  - The capabilities and performance of a UHV system for in situ studies of metal
      semiconductor interactions are described. The UHV system consists of
      interconnected deposition and analysis chambers, each of which is capable of
      maintaining a base pressure of approximately 1 x 10(-10) torr. The deposited
      materials and their reaction products can be studied in situ with RHEED, XAFS,
      AES, XPS, UPS and ARUPS. Results from a study of the reaction of 0.7- and 1.7
      monolayer-thick films of cobalt with strained silicon-germanium alloys are
      presented. The signal-to-noise ratio obtained in these experiments indicates that
      the apparatus is capable of supporting in situ EXAFS studies of approximately 0.1
      monolayer-thick films.

PMID- 15263742
TI  - Inelastic X-ray scattering in molecular liquids and electron correlation effects.
AB  - Inelastic X-ray scattering spectra of liquid water and cyclohexane have been
      measured with 2 eV resolution for a momentum transfer range between 0.69 and 2.77
      au at BL16A of the Photon Factory, KEK, Tsukuba. Observed spectra are transformed
      to the dynamic structure factor which is normalized by using the Bethe sum rule,
      and the static structure factor is obtained. From a comparison with extended CI
      calculations by the use of various basis sets, correlation effects are proved to
      be of vital importance in inelastic X-ray scattering.

PMID- 15263743
TI  - X-ray triple refraction and triple absorption in a cobalt-complex crystal.
AB  - X-ray triple refraction and triple absorption have been quantitatively measured
      for the first time. The samples were (100)-, (010)- and (001)-oriented plates of
      a cobalt-complex monoclinic crystal. The apparatus used was an energy-tunable X
      ray polarimeter with a phase retarder. The X-ray energy was scanned over a range
      of 150 eV near the cobalt K-absorption edge. Both the spectra of ellipticity and
      rotation of polarization were completely different for each crystal plate, which
      revealed that the biaxial crystal had three refractive indices and three
      absorption coefficients in the X-ray region. The Kramers-Kronig relation between
      the real and imaginary parts of the dielectric anisotropy has been quantitatively
      confirmed for all three different orientations.

PMID- 15263744
TI  - Experimental apparatus for the study of photoabsorption processes of multiply
      charged ions by synchrotron radiation.
AB  - Photon-ion merged-beam apparatus using a compact ECR ion source and a high
      brilliance light source has been designed for the study of photoabsorption
      processes of multiply charged ions. Photoion spectroscopy will be performed along
      isoelectronic, isonuclear and isoionic sequences. The main features of this
      apparatus are described.

PMID- 15263745
TI  - Local structure study of dilute Er in III-V semiconductors by fluorescence EXAFS.
AB  - For understanding the luminescence of Er atoms in III-V semiconductors, OMVPE
      grown InP doped with Er has been investigated by fluorescence EXAFS (extended X
      ray absorption fine structure) in order to study the local structure around Er
      atoms. The local structures around the Er atoms doped in InP, with doping as
      dilute as 3 x 10(12) Er atoms in a 1.5 mm x 1.0 mm spot, were successfully
      measured by fluorescence EXAFS. The EXAFS analysis revealed that the Er atoms
      doped in InP above 853 K (which showed low luminescence) formed the rock-salt
      structure ErP, while the Er atoms doped in InP below 823 K (which showed high
      luminescence) substituted on the In site of InP. The dependence of the local
      structure on growth temperature was observed for the samples doped with 3 x
      10(12) atoms and 1.2 x 10(13) atoms of Er.

PMID- 15263746
TI  - Trace element analysis on Si wafer surfaces by TXRF at the ID32 ESRF undulator
      beamline.
AB  - Synchrotron radiation total-reflection X-ray fluorescence (SR-TXRF) has been
      applied to the impurity analysis of Si wafers using a third-generation
      synchrotron radiation undulator source. A lower limit of detectability (LLD) for
      Ni atoms of 17 fg (1.7 x 10(8) atoms cm(-2)) has been achieved with an optical
      set-up based on an Si(111) double-crystal monochromator and a horizontal sample
      geometry. These first results are very promising for synchrotron radiation trace
      element analysis since we estimate that it is possible to lower the LLD by a
      factor of about 25 by employing appropriate optics and detectors. The use of a
      crystal monochromator opens new possibilities to perform absorption and
      scattering experiments (NEXAFS and X-ray standing-wave methods) for chemical and
      structural analysis of ultratrace elements.

PMID- 15263747
TI  - Mn Lalpha,beta and F Kalpha resonant X-ray fluorescence spectroscopy of MnF(2).
AB  - Mn Lalpha,beta and F Kalpha(1,2) (K-L(3,2)) X-ray fluorescence spectra of MnF(2)
      were measured when the excitation X-ray energy was higher and lower than the
      threshold energies. Monochromated synchrotron radiation was used for primary
      excitation. The resonance fluorescence of Mn Lbeta and the multiply ionized F
      Kalpha(3,4) satellites (KL-L(2)) were observed.

PMID- 15263748
TI  - Laser-induced fluorescence excitation spectroscopy of N(2)(+) produced by VUV
      photoionization of N(2) and N(2)O.
AB  - Synchrotron radiation emitted from the UVSOR storage ring is monochromated by a
      grazing-incidence monochromator and introduced coaxially with the second harmonic
      of a mode-locked Ti:sapphire laser. Sample gases, N(2) and N(2)O, are
      photoionized into vibronically ground N(2)(+) with the fundamental light of the
      undulator radiation at 18.0 and 18.6 eV, respectively. Laser-induced fluorescence
      (LIF) excitation spectra of N(2)(+) from N(2) and N(2)O are measured in the laser
      wavelength region of the (B (2)Sigma(u)(+), v' = 0) <-- (X (2)Sigma(g)(+), v" =
      0) transition at 389-392 nm. The LIF excitation spectra of N(2)(+) exhibit two
      maxima due to the P and R branches in which rotational bands are heavily
      overlapped. The rotational temperature is determined by simulating an LIF
      excitation spectrum by using the theoretical intensity distribution of rotation
      bands convoluted with the spectral width of the laser.

PMID- 15263749
TI  - Application of synchrotron radiation to ultrafast spectroscopy.
AB  - A novel application of synchrotron radiation to ultrafast optical spectroscopy is
      demonstrated. The application is based on the short coherence time of broadband
      synchrotron radiation and employs a conventional interferometer. From a detailed
      study of the coherence of synchrotron radiation, it is shown that the coherent
      interference between two synchrotron radiation beams, split from a single beam,
      can provide ultimate time resolution down to a few femtoseconds. Experimental
      results of ultrafast spectroscopy using broadband synchrotron radiation are
      presented; these include free-induction decay and photon echoes in the visible
      and ultraviolet regions.

PMID- 15263750
TI  - Time-resolved fluorescent X-ray interference.
AB  - A fluorescent X-ray interference method can effectively measure nanometer-level
      conformational changes for non-crystallized molecules and proteins in aqueous
      conditions. The time-resolved technique can be used to obtain information about
      the dynamics of molecules and proteins. Instrumentation for time-resolved
      fluorescent X-ray interference has been designed. A typical interference-fringe
      pattern was observed with approximately 3 s of X-ray exposure time from K
      fluorescent X-rays emitted from a Zn monoatomic layer on an Rh substrate. The
      primary X-ray beam was polychromed with a mirror for total external reflection of
      X-rays and was tuned to an energy level at which only Zn K radiation became
      optimally excited. The glancing angle of the primary X-ray beam was fixed at a
      glancing angle at which the total intensity of K-fluorescent X-rays emitted from
      Zn atoms corresponded to the maximum value. The fluorescent X-ray interference
      fringes were monitored with an imaging plate (IP) as a non-energy-dispersive two
      dimensional detector. The exposed interference fringes on the IP were integrated
      along the direction of the fringes. The integrated fringes were in close
      agreement with a theoretical estimate based on the interference among transmitted
      and reflected waves at interfaces in the sample.

PMID- 15263751
TI  - High-resolution X-ray topographic images of dislocations in a silicon crystal
      recorded using an X-ray zooming tube.
AB  - A Be-window-type X-ray zooming tube is an X-ray digital imaging system whose
      magnification factor of X-ray images can be easily varied from 10 to 200, and
      whose spatial resolution is less than 0.5 micro m. This zooming tube was used as
      an imaging detector in double-crystal X-ray topography to obtain high-resolution
      images of dislocations in a silicon crystal. X-ray interference images of about 5
      micro m were observed even though optimal performance of the X-ray zooming tube
      could not be achieved. The results indicate that the X-ray zooming tube might
      make a good detector for X-ray topography with minor improvements in its stage
      structure.

PMID- 15263752
TI  - The white-radiation dynamic topography experimental system at the BSRF.
AB  - A white-radiation dynamic topography experimental system has been established at
      the BSRF (Beijing Synchrotron Radiation Facility) and is now in operation. Each
      part of this system is described in this paper, with particular emphasis given to
      the PC-based online control system, the X-ray video-imaging system and the image
      treatment system. Moreover, some of the experimental results, such as the phase
      transition of KNbO(3) nonlinear optical crystals and of blue bronze charge
      density-wave material, are briefly presented.

PMID- 15263753
TI  - A bent Laue analyser crystal for Rayleigh-to-Compton computed tomography.
AB  - A new optical system to perform tomography based on the Rayleigh-to-Compton (RC)
      method with high spatial and spectral resolution is presented. The RC technique
      allows the effective atomic number of a sample to be measured and finds
      application in bone mineral densitometry in medicine. It is particularly useful
      for the characterization of the distribution of biological materials which do not
      exhibit distinctive diffraction peaks. The system is based on the separation of
      the elastic line from the spectrum that is scattered by the sample by means of a
      bent Laue analyser crystal, and the subsequent independent detection of the
      elastic and inelastic parts of the spectrum with two large-area scintillation
      counters. The high energy resolution permits operation at low momentum transfer,
      where the RC method has its best contrast-to-noise ratio for low-Z materials. The
      geometrical and spectral requirements in terms of the incident beam and the
      conical analyser crystal are discussed. A first-generation tomographic imaging
      system (pencil beam, scanned sample) as implemented at the ESRF Compton
      Scattering Station ID15B is described. A high-resolution tomographic
      reconstruction of a bone sample is presented.

PMID- 15263754
TI  - Three-dimensional tomography using a soft X-ray holographic microscope and CCD
      camera.
AB  - The depth resolution of a soft X-ray hologram is much worse than its transverse
      resolution because a single soft X-ray hologram has a small numerical aperture.
      To obtain a three-dimensional image, in-line holograms of a specimen were
      recorded from various directions and reconstructed to obtain two-dimensional
      projection data. Then, a three-dimensional reconstruction was performed by back
      projection of these reconstructed holograms. Three-dimensional images of a
      tungsten wire of diameter 10 micro m and a fossil of a diatom were obtained.

PMID- 15263756
TI  - X-ray wideband in-line holography using a zone plate.
AB  - X-ray wideband in-line holography, a new X-ray holography geometry using a zone
      plate, is proposed. The temporal coherence requirement in this geometry can be
      very low.

PMID- 15263755
TI  - Development of scanning X-ray microscopes for materials science spectromicroscopy
      at the Advanced Light Source.
AB  - The development of two zone-plate microscopes for X-ray spectroscopic analysis of
      materials is described. This pair of instruments will provide imaging NEXAFS
      analysis of samples in transmission at atmospheric pressure and imaging XPS and
      NEXAFS analysis of sample surfaces in a UHV environment.

PMID- 15263757
TI  - Deep X-ray lithography with a tunable wavelength shifter at CAMD.
AB  - An additional X-ray lithography facility is under construction at the Center for
      Advanced Microstructures and Devices. It will receive radiation from a 7.5 T
      superconducting three-pole wavelength shifter. The critical energy of the
      insertion device is tunable up to a maximum value of 11.2 keV, allowing for
      optimization of photon spectra to resist thickness. In particular, this hard X
      ray source will allow investigation of X-ray lithography at very high energies
      for devices with thicknesses in excess of 1 mm, and study of low-cost mass
      production concepts, using simultaneously exposed stacks of resist layers.

PMID- 15263758
TI  - X-ray contact microscopy system for spectromicroscopy of biological specimens.
AB  - An X-ray contact microscopy system has been developed for the study of molecular
      and elemental distributions in biological specimens based on X-ray absorption
      characteristics. The system consists of a chamber for measuring XANES (X-ray
      absorption near-edge structure) of biomolecules, and a contact microscopy system
      for dried specimens with an electronic zooming tube. With this system the
      elemental distribution of carbon, nitrogen, oxygen, Ca and Fe in an HeLa cell has
      been studied, and the DNA-related image using a peak from the XANES profile of
      the DNA at the K-absorption edge of phosphorus has been obtained.

PMID- 15263759
TI  - Imaging soft X-ray microscope at Rits Synchrotron Radiation Center.
AB  - An imaging soft X-ray microscope with zone plates has been installed at Rits SR
      Center (Ritsumeikan University, Kusatsu, Japan). With this microscope, specimens
      were set in air, which made it possible to investigate the specimens without
      breaking the vacuum of the microscope. The specimens can be prefocused with an
      optical microscope. Dry and wet biospecimens in air were observed. A new optical
      system was designed to improve the resolution.

PMID- 15263760
TI  - Studies on intracellular structures of COS cells by X-ray microscopy.
AB  - COS-7 cells, fixed with glutaraldehyde, were studied using the transmission X-ray
      microscope at the electron storage ring BESSY, Berlin. The border of the cell,
      the nucleus, nucleoli and mitochondria of the cells were clearly visualized with
      the X-ray microscope. In addition, we found many X-ray dense granules
      preferentially located around the nucleus. Electron microscopy showed that
      numerous multivesicular bodies, whose structures belong to the endosome-lysosomal
      system, were present around the nucleus. The size and localization patterns of
      the X-ray dense granules were quite similar to those of multivesicular bodies.
      These results strongly suggest that the X-ray dense granules are multivesicular
      bodies.

PMID- 15263761
TI  - Development of X-ray photoemission electron microscopy (X-PEEM) at the SRS.
AB  - The use of synchrotron radiation sources for X-ray spectroscopy is a well known
      and developed field. The majority of applications, however, have been limited to
      studies of materials containing only a single phase of the element of interest.
      Owing to limited availability of suitable instrumentation, the study of materials
      comprising intergrowths of different phases has presented difficulties in
      analysis. The majority of natural materials, including mineralogical samples,
      fall into this category. However, by applying the technique of photoemission
      electron microscopy (PEEM) to view the X-ray stimulated photoemission generated
      at an absorption edge, micro-area-selectable spectroscopy becomes possible. An
      instrument for X-ray PEEM (X-PEEM) is being developed at the Daresbury SRS and
      this paper shows how it can be used to obtain characteristic L-edge XANES spectra
      from finely intergrown iron oxide minerals.

PMID- 15263762
TI  - Submicrometre-area high-energy-resolution photoelectron spectroscopy system.
AB  - A submicrometre-area photoelectron spectroscopy system that uses a multi-layer
      coated Schwarzschild objective as the soft X-ray microbeam optics has been
      developed. The system is located at an undulator beamline (BL-16U) at the Photon
      Factory in the High Energy Accelerator Research Organization. By knife-edge
      measurement, the microbeam size was estimated to be 160 nm at the sample position
      using a 25-75% criterion. Photoelectron spectral measurements revealed that the
      Fermi edge width was 0.12 eV, which means that the instrumental resolution was
      0.05 eV, after removing the natural broadening of the Fermi edge at room
      temperature. This system offers both high energy resolution and high spatial
      resolution.

PMID- 15263763
TI  - X-ray microprobe system for XRF analysis and spectroscopy at SPring-8 BL39XU.
AB  - An X-ray microprobe system for X-ray fluorescence (XRF) analysis and spectroscopy
      has been developed at SPring-8 BL39XU; it comprises an X-ray focusing or
      collimation system, energy-dispersive (ED) and wavelength-dispersive (WD) XRF
      spectrometers, and a sample-scanning system. The conventional ED spectrometer
      will be utilized for qualitative and quantitative trace-element analysis, and the
      WD spectrometer will be used both for trace-element analysis and XRF
      spectroscopy. A combination of monochromated undulator radiation and the WD
      spectrometer will enable resonant XRF spectroscopy using brilliant hard X-ray
      undulator radiation.

PMID- 15263764
TI  - Imaging X-ray fluorescence microscope with a Wolter-type grazing-incidence
      mirror.
AB  - A Wolter-type grazing-incidence mirror was used as an objective for an imaging X
      ray fluorescence microscope. The microscope was constructed at the beamline 6C2
      of the Photon Factory. The shortest wavelength used was approximately 0. 1 nm,
      which was limited by the grazing-incidence angle of the mirror. To demonstrate
      the possibility of recording X-ray fluorescence images, several fine grids were
      used as test specimens. Characteristic X-rays emitted from each specimen could be
      clearly imaged. Spatial resolution was estimated to be better than 10 micro m.

PMID- 15263765
TI  - Development of an ultra-fast data-acquisition system for a two-dimensional
      microstrip gas chamber.
AB  - A high-performance data-acquisition system has been developed in order to obtain
      time-resolved sequential images from a two-dimensional microstrip gas chamber
      (MSGC). This was achieved using fully digital processing with a synchronized
      pipeline method. Complex logical circuits for processing large numbers of signals
      are mounted on a small number of complex programmable logic devices. The system
      is operated with a 10 MHz synchronous clock, and has the capability of handling
      more than 3 x 10(6) counts s(-1) for asynchronous events. The system was examined
      using a 5 x 5 cm MSGC and the recently developed 10 x 10 cm MSGC (1024 outputs);
      the anticipated performances were achieved.

PMID- 15263766
TI  - Development of a two-dimensional imaging system for clinical applications of
      intravenous coronary angiography using intense synchrotron radiation produced by
      a multipole wiggler.
AB  - A two-dimensional clinical intravenous coronary angiography system, comprising a
      large-size view area produced by asymmetrical reflection from a silicon crystal
      using intense synchrotron radiation from a multipole wiggler and a two
      dimensional detector with an image intensifier, has been completed. An advantage
      of the imaging system is that two-dimensional dynamic imaging of the
      cardiovascular system can be achieved due to its two-dimensional radiation field.
      This world-first two-dimensional system has been successfully adapted to clinical
      applications. Details of the imaging system are described in this paper.

PMID- 15263767
TI  - Bronchography test studies at the angiography station of the VEPP-3 storage ring.
AB  - The K-edge dichromography method was applied for preliminary bronchography test
      studies at the angiography station on the VEPP-3 storage ring. Images of xenon
      distribution over the test sample of Plexiglass were acquired. The obtained
      results demonstrate that thicknesses of xenon as small as 0.5 mm can be
      visualized.

PMID- 15263768
TI  - High-spatial-resolution and real-time medical imaging using a high-sensitivity
      HARPICON camera.
AB  - A HARPICON(TM) camera has been applied to a digital angiography system with
      fluorescent-screen optical-lens coupling. It uses avalanche multiplication in the
      photoconductive layer for high-sensitivity imaging. The limiting spatial
      resolutions in the 1050 scanning-line mode of the camera are about 30 and 50
      micro m at input field sizes of 20 x 20 and 50 x 50 mm on the screen,
      respectively. For high-speed imaging, the 525 scanning-line mode at a rate of 60
      images s(-1) can be selected. High-quality images of coronary arteries in dogs
      were obtained by intra-aortic coronary angiography and superselective coronary
      angiography using a single-energy X-ray above the iodine K-edge energy.

PMID- 15263769
TI  - Phase-contrast X-ray CT image of breast tumor.
AB  - Phase-contrast X-ray CT images generated by differences in refractive indices can
      be used to visualize the internal structures of soft tissues without contrast
      enhancement. In this study, imaging of human breast tumor was performed on
      formalin-fixed samples. Experiments were carried out at the synchrotron source of
      the Photon Factory, Tsukuba, Japan. The X-ray energy was adjusted to 17.7 keV.
      Phase-contrast X-ray CT images revealed various structures of human breast tumor
      as clearly as optical images.

PMID- 15263770
TI  - Application of synchrotron radiation in investigation of metal-ion release from a
      hip replacement prosthesis.
AB  - The aim of the present study was to measure very low concentrations of Al, V, Fe,
      Cr and other metal elements in a matrix of P, S, Cl, Ca and other constituent
      elements of the human body. These metal elements were released from a failed
      total hip replacement prosthesis into the surrounding tissues. The experimental
      results have been compared with those from proton-induced X-ray emission
      spectroscopy of the same specimen.

PMID- 15263771
TI  - Rapid projection of crystal grain orientation distribution in aluminium alloy
      sheets by synchrotron X-ray diffraction.
AB  - An investigation of the primary recrystallization and the grain growth process of
      aluminium alloy sheets has been carried out using a method for rapid projection
      of the crystal grain orientation distribution. It is found that the projected
      pattern is continuous in the cold-rolled state. When the sheet is annealed, tiny
      diffraction spots or small grains appear. The addition of Mg greatly alters the
      sizes and number of grains, and the orientation of the grains in sheets.

PMID- 15263772
TI  - Synchrotron-radiation-induced formation of salt particles on an X-ray lithography
      mask.
AB  - The suppression and removal of contaminants on X-ray masks are required for the
      application of X-ray lithography to practical semiconductor production, because
      contamination is easily transferred to the replicated resist patterns and
      degrades the LSI patterns. In order to study contamination of a Ta/SiN X-ray
      mask, its growth process was investigated using an atmospheric reaction chamber
      and in situ observation apparatus for gases at atmospheric pressure. It was found
      that the contamination particles were ammonium sulfate and oxalate. The sources
      of the salt particle were also identified.

PMID- 15263773
TI  - XAFS spectra from reflectivity measurements.
AB  - The reflectivity of TiSi(2) films was measured as a function of photon energy E
      at the Ti K-edge region at a glancing angle theta close to the critical angle
      theta(C) of total reflection. TiSi(2) silicide films (about 30 nm thickness) were
      prepared by silicidation of Ti thin films deposited on Si(001) substrates. Since
      the Fresnel reflectivity R(theta,E) is a function of the dispersion delta(E) and
      of the absorption beta(E), the absorption beta(E) which carries the XAFS signal
      can be solved as beta(theta,delta,R) for observed reflectivity R and for
      estimated delta. The dispersion delta(E) is related to the absorption beta(E) by
      the Kramers-Kronig (K-K) relations since the refractive index is n(E) = 1 -
      delta(E) - ibeta(E). beta(E) was calculated from the observed reflectivity
      R(theta,E) using theoretical values for initial delta(E). Titanium K-edge XAFS
      for TiSi(2) was extracted from the reflectivity by 'ReflXAFS'.

PMID- 15263774
TI  - X-ray absorption fine structure of V(2)O(5) and Li(x)V(2)O(5).
AB  - Vanadium K-edge XAFS measurements of five compounds were carried out. The
      compounds studied were crystalline V(2)O(5) and four types of Li(x)V(2)O(5) with
      different insertion levels x, which show different EMFs (2.0-3.4 V). The EXAFS
      data analysis shows no remarkable difference in the V-O distances in the five
      compounds, showing that the structure of the VO(5) square pyramids changes only
      slightly as lithium atoms are intercalated into the V(2)O(5). In the XANES
      spectra, three peaks are observed for crystalline V(2)O(5) and Li(x)V(2)O(5) (3.4
      V). When the EMF is decreased, the intensity difference between the first and
      second peaks disappears and the third peak shifts to lower energy. The XANES data
      were analysed using full multiple-scattering calculations. In the calculated
      spectra the intensity of the first peak increases as the V(2)O(5) intercalates
      lithium atoms.

PMID- 15263775
TI  - Design of beamline optics for EUVL.
AB  - The design of front-end collimating optics for extreme-ultraviolet lithography
      (EUVL) is reported. For EUVL, collimating optics consisting of a concave toroidal
      mirror and a convex toroidal mirror can achieve shorter optical path lengths than
      collimating optics consisting of two concave toroidal mirrors. Collimating optics
      consisting of a concave toroidal mirror and a convex toroidal mirror are
      discussed. The design of collimating optics for EUVL beamlines based on ray
      tracing studies is described.

PMID- 15263776
TI  - Synchrotron radiation direct photo-etching of polymers and crystals for
      micromachining.
AB  - Synchrotron radiation etching of polymers and optical crystals which are
      transparent throughout the spectral range from visible to ultraviolet has been
      carried out without using any chemicals, successfully creating high-aspect-ratio
      microstructures for micromachining. A detailed study of the etching rates by
      varying the synchrotron beam current, sample temperature, beam size and aspect
      ratio showed that this synchrotron radiation process is essentially different
      from laser ablation, while an in situ mass spectrometric analysis of gaseous
      etching products showed that the dissociation mechanism involved with the
      synchrotron radiation processing, even with heating, is completely different from
      the thermal dissociation of the laser ablation.

PMID- 15263777
TI  - Commissioning and operation of the first brazilian synchrotron light source.
AB  - The synchrotron light source designed and constructed at the LNLS is composed of
      a 1.37 GeV electron storage ring and a 120 MeV linac for low-energy injection.
      The storage ring has been commissioned and has already reached the designed
      electron-beam energy, current and emittance. The electron lifetime is now 6 h at
      60 mA, and is steadily increasing. Seven beamlines (TGM, SGM, SXS, XAFS, XRD,
      SAXS, PCr) have been constructed in parallel with the electron accelerators and
      are at present in operation. Beam time was allocated to 129 approved research
      projects for the second semester of 1997. A number of them are currently under
      way.

PMID- 15263778
TI  - Compact superconducting ring at ritsumeikan university.
AB  - A compact superconducting storage ring (0.575 GeV and 300 mA) with a racetrack
      microtron injection system was installed at Ritsumeikan University and has been
      operated successfully since April 1996. As the radius of the circular electron
      orbit is small (0.5 m), it is possible to use a radiation beam of relatively high
      photon flux at a short distance from the source point. Beamlines have been
      constructed including those for XAFS, soft X-ray spectroscopy, VUV spectroscopy,
      fluorescent X-ray analysis, soft X-ray microscopy, X-ray diffraction/scattering
      and photoelectron spectroscopy; the photoelectron spectrometer is combined with
      an ion-beam-scattering spectrometer to obtain information both on the electronic
      states and on the atomic arrangements of a solid surface. In addition there are
      two beamlines, one for LIGA exposure and the other for synchrotron radiation
      ablation, which are devoted to producing new devices and materials. The
      synchrotron radiation facility is open not only to users in the University but
      also to researchers in industry, governmental institutions and other
      universities.

PMID- 15263779
TI  - Present Status of the UVSOR Facility - 1997.
AB  - The UVSOR has been operational for nearly 14 years. In recent years, improvements
      to accelerators and beamlines have been carried out to obtain better performance
      and new scientific achievements. For example, a new type of helical undulator and
      a resonance transverse kicker were installed into the straight sections of the
      storage ring, and about one-third of the beamlines were upgraded by installing
      new monochromators and an interferometer. In addition, instruments and equipment
      were improved for research studies, with many interesting results. The most up-to
      date information of the UVSOR facility is presented.

PMID- 15263780
TI  - NSRL Phase II Project (a Brief Introduction and Status).
AB  - The Phase II Project is to be launched soon at NSRL, People's Republic of China.
      The main purpose of the project, an outline of its upgrade/expansion plans, and
      its present status are briefly described.

PMID- 15263781
TI  - The siam photon laboratory.
AB  - A synchrotron radiation research project, the Siam Photon Project, is underway in
      Thailand. The light source used in the project is the modified SORTEC storage
      ring. The project and simple aspects of the light source are described. The
      detailed design of the building to accommodate the experimental hall and the
      light source has been accomplished and the construction will start soon. The
      engineering design work of the machine components necessary for the modifications
      to reduce the beam emittance and to make the installation of insertion devices
      possible is underway.

PMID- 15263782
TI  - The Hiroshima Synchrotron Radiation Center (HSRC).
AB  - The history of HSRC is briefly sketched, going back to the early HiSOR project.
      The present status of this 0.7 GeV compact storage ring is described and an
      outline of the future of the facility is given in the context of western Japan.

PMID- 15263783
TI  - Lichen sclerosus of the male genitalia and urethral stricture diseases.
AB  - INTRODUCTION: The true incidence of urethral involvement in patients with genital
      lichen sclerosus (LS) is unknown. We review the epidemiology and discuss the
      pathogenesis of LS and urethral stricture diseases. MATERIALS AND METHODS: During
      the period 1991-2002, of 925 patients who underwent urethroplasty for anterior
      urethral stricture, 130 patients (14%) received the diagnosis of LS. In all
      patients with LS the histology was re-examined to confirm the clinical diagnosis.
      Retrograde and voiding urethrography was used to establish urethral involvement
      in the disease. RESULTS: In 106 patients (82%) the histology provided the
      classical features of LS, and 24 patients (18%) showed some histological
      variations. In 49 patients (37%) the LS involved the pendolous urethra (meatus
      navicularis-penile), and in 53 cases (41%) a panurethral stricture was evident.
      CONCLUSIONS: LS urethral involvement appears to be a much more common and
      extensive disease than previously reported, and requires particular care in its
      early diagnosis.

PMID- 15263784
TI  - Bladder outlet obstruction in women: difficulties in the diagnosis.
AB  - OBJECTIVE: To identify the difficulties in diagnosing bladder outlet obstruction
      in women. MATERIAL AND METHODS: 53 women with a mean age of 37.2 (range 16-70)
      with chronic lower urinary tract symptoms and no neurogenic or organic diseases
      were examined. The prevalent symptoms were frequency (96%), urgency (92%) and
      nocturia (75%), and the mean duration of symptoms was 3.8 years. After pressure
      flow studies and voiding cystourethrography were conducted, patients either
      underwent bladder neck or urethral incisions based on their diagnosis. These
      patients were subsequently subjected to follow-up uroflow studies. RESULTS:
      Abnormal uroflow curves were observed in 19 of 53 women. In 10 of them (52.6%),
      bladder outlet obstruction based on pressure-flow results was confirmed. Voiding
      cystourethrography results from these 19 women confirmed that 17 patients had
      bladder neck obstruction, while the remaining 2 had urethral obstruction. 16 of
      19 were treated endoscopically, with 14 patients undergoing bladder neck
      incisions through the 5- and 7-o'clock positions and 2 patients having a distal
      urethral incision through the 12-o'clock position. In all of these 16 cases,
      there were both a statistical increase in the maximum flow rate (Qmax) as well as
      an improvement in the flow curves. Symptomatic improvement was observed in 12 of
      the 16 women subjected to surgical intervention. CONCLUSION: Bladder outlet
      obstruction exists in women with lower urinary tract symptoms. Pressure-flow
      studies and voiding cystourethrography are reliable modalities for confirming
      bladder outlet obstruction. Bladder outlet obstruction can be functionally or
      structurally caused.

PMID- 15263785
TI  - Long-term results of Anderson-Hynes pyeloplasty in 180 adults in the era of
      endourologic procedures.
AB  - INTRODUCTION: The aim of the present study wasto evaluate the long-term results
      of adult open pyeloplasties performed by the Anderson-Hynes technique in the era
      of new endourologic procedures. MATERIALS AND METHODS: The medical records of 180
      adult patients who underwent Anderson-Hynes pyeloplasty with a diagnosis of
      ureteropelvic junction (UPJ) obstruction, were retrospectively reviewed. Pre- and
      postoperative results were compared with clinical, radiologic and radionuclide
      studies. The mean age of the patients was 33.2 (16-65) years. The minimum
      clinical follow-up time was 12 months and the mean time from the operation was
      9.4 years (between 1 and 17 years). RESULTS: Success was defined as resolution of
      symptoms and decrease in pyelocaliceal volume and calicectasis. The overall
      success rate was 91.1%. The success rate was between 93.1 and 100% in patients
      with grades I-III and 62.5% in patients with grade IV hydronephrosis and
      contribute to renal function less than 25%. The pyelocaliceal volume returned to
      normal in 39 (21.7%) patients, significantly decreased in 82 (45.5%), and the
      flow of contrast media from renal pelvis to ureter improved in 43 (23.9%) and did
      not change or increased in 16 (8.9%). The failure happened in the first 3 months
      in 57% of patients and in long-term follow-up in 43% of patients. CONCLUSION:
      Despite newer endoscopic techniques, Anderson-Hynes pyeloplasty, with an over 90%
      success rate remains the gold standard in the treatment of primary UPJ
      obstruction.

PMID- 15263786
TI  - A novel antireflux technique using an intussuscepted ileal segment.
AB  - A novel surgical technique of antireflux with an ileal conduit for urinary
      diversion is presented with our early results. The mid 8-cm portion of an
      isolated terminal ileum is intussuscepted. After skeletonization of the
      mesenterial vasculature, 3 rows of 4 mattress seromuscular silk sutures are
      placed on the ileum. By tying the sutures successively, the ileum is
      intussuscepted and the resultant nipple is secured simultaneously between its
      outer and inner layers. The outer nipple layer and the recipient ileal layer are
      further fixed as a whole by placing 3 rows of metal staples. The nipple base is
      secured by interrupted silk sutures and the mesenterial defect is closed. This
      technique was applied to 30 patients undergoing rectosigmoidal bladder procedure,
      a modified ileocecal rectal bladder, in which the antireflux conduit was
      interposed between the ureters and the rectosigmoidal pouch. Ureteral reflux was
      observed in none of the patients during a mean follow-up period of 29.9 months.
      Of the 60 renal units, 53 (88.3%) had normal pyelography and 7 (12.7%) showed
      mild hydronephrosis at 3-6 months postoperatively. This antireflux technique is
      simple and reliable, and can be applied to other urinary diversion/reconstruction
      surgeries, such as the continent reservoir, orthotopic neobladder, and/or bladder
      augmentation.

PMID- 15263787
TI  - Standard versus hydrophilic catheterization in the adjuvant treatment of patients
      with superficial bladder cancer.
AB  - INTRODUCTION: The aim of the present study is to compare a hydrophilic catheter
      to the standard polyvinyl chloride catheter with regard to bacteriological safety
      and overall comfort in patients undergoing intravesical immuno- or chemotherapy
      for bladder cancer. MATERIALS AND METHODS: One hundred patients (80 males, 20
      females; median age 65.8 years, range 48-79 years) eligible for intravesical
      prophylaxis of superficial bladder cancer recurrences were randomized to receive
      intravesical therapy using a standard catheter (group A, n = 50) or a hydrophilic
      catheter (group B, n = 50). Urinalysis and urine culture were performed 2 days
      after catheterization. Comfort during catheterization was assessed by a 5-point
      visual analogue scale at the end of the first four instillations. RESULTS:
      Urinary tract infection (UTI) was detected in 7.4% of catheterizations in group
      A, whereas it occurred in 3.5% of catheterizations in group B (p < 0.01).
      Escherichia coli was the most frequent pathogen regardless of the device used. At
      the end of each of the first four instillations, the mean score for discomfort
      was significantly higher in group A than in group B (p < 0.001), although
      catheterization was progressively better tolerated regardless of the device used
      (both p < 0.005). None of the patients were found to be suffering from orchitis,
      epididymitis or gross haematuria. CONCLUSION: Hydrophilic catheters may be used
      safely and are well tolerated by patients undergoing intravesical immuno- or
      chemotherapy. The hydrophilic catheter was associated with a significantly lower
      occurrence of UTI and higher acceptability compared to the standard device. These
      data should be considered with regard to patient compliance with intravesical
      therapy.

PMID- 15263788
TI  - Fine-needle aspiration cytology of the testis: can it be a single diagnostic
      modality in azoospermia?
AB  - PURPOSE: The aim of this study was to determine whether fine-needle aspiration
      cytology (FNAC) of testis alone is sufficient to diagnose testicular function and
      whether follicle-stimulating hormone (FSH) estimation can be safely eliminated
      from the evaluation protocol of the azoospermic subject. MATERIALS AND METHODS:
      We studied 46 adult azoospermic males who were infertile for more than 2 years
      following marriage. Hormonal profile was done in all. Later all 46 patients were
      subjected to bilateral FNAC of the testes. The cytological findings were
      correlated with histological findings. RESULTS: We found 95.65% agreement between
      FNAC and testicular biopsy. Though serum FSH estimation was done in all patients
      in this series, in none of the cases did it affect overall management.
      CONCLUSION: FNAC is a quick, safe and minimally invasive modality. Following a
      well-performed semen analysis in an azoospermic subject, it appears that FNAC may
      be the only investigation needed. It provides a reliable diagnosis in patients
      with either obstructive or non-obstructive azoospermia. Routine estimation of FSH
      can be omitted from the investigative protocol in these patients.

PMID- 15263789
TI  - Effect of sildenafil citrate on retinal functions: preliminary report on Humphrey
      visual field analysis.
AB  - OBJECTIVE: To assess the effect of sildenafil citrate treatment on visual field
      analysis (VFA) in patients using sildenafil citrate for erectile dysfunction.
      MATERIALS AND METHODS: In this prospective study on 18 male volunteers with
      erectile dysfunction, bilateral VFA was performed using the Humphrey 30-2 central
      standard threshold test. White-on-white (W/W) and blue-on-yellow (B/Y) protocols
      were used prior to treatment (baseline VFA) and after treatment (repeat VFA) with
      sildenafil citrate. W/W and B/Y baseline VFA and repeat VFA mean deviations (MD)
      were compared. RESULTS: The baseline MD for W/W and B/Y protocols were -1.34 +/-
      1.8 and -2.59 +/- 2.1 dB, respectively, whereas the mean repeat MD for W/W and
      B/Y protocols were -1.79 +/- 2.21 and -2.83 +/- 3.31 dB, respectively. There was
      no statistically significant difference between W/W and B/Y baseline and repeat
      VFA with respect to MD (p > 0.05). CONCLUSION: Sildenafil citrate causes no
      significant changes in Humphrey VFA in patients with erectile dysfunction.

PMID- 15263790
TI  - Relation between erectile dysfunction and urinary incontinence after nerve
      sparing and non-nerve-sparing radical prostatectomy.
AB  - INTRODUCTION: We investigated the status of erectile function and urinary
      continence after radical prostatectomy to investigate a possible relation between
      them and then determined whether the status of postoperative urinary continence
      affected erectile function. PATIENTS AND METHODS: Seventy-six patients who had no
      symptoms of erectile dysfunction or urinary incontinence preoperatively were
      included in this study. The postoperative status of erectile function and urinary
      continence was investigated using a self-reported patient questionnaire. RESULTS:
      Thirteen of 27 patients (48.1%) who underwent nerve-sparing procedures maintained
      erectile function, while 7 of 49 patients (14.2%) who underwent non-nerve-sparing
      procedures maintained it postoperatively. None of the 27 patients in the nerve
      sparing procedure group reported incontinence, whereas 3 of the 49 patients
      (6.1%) who underwent non-nerve-sparing procedures reported moderate incontinence.
      However, no significant correlation between the International Index of Erectile
      Function-5 score and the Incontinence Impact Questionnaire score was seen.
      CONCLUSION: No relation between the status of urinary continence and erectile
      function was shown, regardless of the nerve-sparing nature of the prostatectomy.

PMID- 15263791
TI  - E-cadherin expression in prostate adenocarcinomas in Chinese and its pathological
      correlates.
AB  - INTRODUCTION: We examined the E-cadherin expression in prostate adenocarcinomas
      in Chinese to correlate this immunohistochemical marker with histopathological
      features. MATERIALS AND METHODS: Primary adenocarcinomas from 122 radical
      prostatectomy specimens were stained using anti-E-cadherin (HECD-1) antibody. The
      association of E-cadherin expression with serum prostate-specific antigen (PSA),
      pathological stage and Gleason score was assessed by Kendall's tau-b test.
      RESULTS: Aberrant E-cadherin expression was identified in 79 tumors (64.8%).
      Abnormal E-cadherin expression did not correlate to serum PSA (p = 0.802), tumor
      stage (p = 0.684) and Gleason score (p = 0.385). CONCLUSIONS: The frequency of
      aberrant E-cadherin expression was higher in prostate adenocarcinomas of Chinese
      as compared to that reported in Caucasians. No association with pathological
      stage, Gleason score and serum PSA was identified.

PMID- 15263792
TI  - p53 gene codon 72 polymorphism but not tumor necrosis factor-alpha gene is
      associated with prostate cancer.
AB  - OBJECTIVE: A polymorphism of gene p53 codon 72 is associated with various cancer
      formations. Tumor necrosis factor-alpha (TNF-alpha) one of the cytokines secreted
      by macrophages in response to inflammation and is also related to cancer
      formation. We aimed to evaluate the association between prostate cancer and the
      polymorphisms of the TNF-alpha gene promoter -308 and p53 gene codon 72. PATIENTS
      AND METHODS: In our study, a normal control group of 126 healthy people and 96
      patients with prostate cancer were examined. The polymorphism (G/A) of TNF-alpha
      gene was detected by polymerase chain reaction (PCR)-based restriction analysis
      (Nco I endonuclease) and the polymorphism of p53 gene was detected by two PCRs
      (one for proline and one for arginine form). RESULTS: There was a significant
      difference in the distribution of codon 72 polymorphism the p53 gene between
      prostate cancer patients and the normal controls (p < 0.001). The proline form of
      p53 gene codon 72 was significantly higher than the arginine form, with an odds
      ratio of 2.606 (95% CI = 1.052-6.455). This difference was also revealed in the
      tumor staging (p = 0.035) as the proline form was significantly higher in the
      metastasis group of prostate cancer. There were no statistical differences in the
      distribution of -308 polymorphism of the TNF-alpha gene between cancer patients
      and the control subjects (p = 1.0). CONCLUSION: Prostate cancer appears to be
      associated with the p53 gene codon 72 polymorphisms, but not with the TNF-alpha
      gene. The proline form of p53 gene codon 72 might be a more significant risk
      factor for the development of metastasis than the arginine form.

PMID- 15263793
TI  - All-trans retinoic acid and interferon-alpha for treatment of human renal cell
      carcinoma multicellular tumor spheroids.
AB  - INTRODUCTION: Conventional preclinical investigations have strongly recommended
      to combine interferon-alpha (IFN-alpha) with 13-cis retinoic acid (13-cRA,
      isotretinoin) for treatment of renal cell carcinoma (RCC). However, a recent
      randomized controlled trial on the drug combination ultimately failed to
      demonstrate an increased tumor-specific survival of patients with metastatic RCC
      (MRCC). All-trans retinoic acid (ATRA, tretinoin) was suggested to provide
      stronger antineoplastic properties than 13-cRA in different other tumors.
      MATERIALS AND METHODS: The present study aimed to compare ATRA with 13-cRA (0.1,
      1, 10, 100 nM) alone or in combination with IFN-alpha (5, 400, 5,000, 25,000,
      250,000 IU/ml) or 5-fluorouracil (5-FU; 0.1, 1, 10, 100 microg/ml). Multicellular
      tumor spheroids of human RCC cells (SN12C) were treated in order to facilitate
      the predictions of the model system. RESULTS: ATRA decreased the mean volume of
      SN12C spheroids 10-20% more than 13-cRA. Both retinoids led to a super-additive
      growth inhibition in combination with IFN-alpha, but not with 5-FU. However, in
      this scenario the superior effect of ATRA compared to 13-cRA, although
      statistically significant, was not impressive (<10%). CONCLUSIONS: ATRA provides
      a slightly stronger direct antineoplastic effect on human renal cancer cells than
      13-cRA, and acts synergistically with IFN-alpha. However, ATRA, if at all, does
      not seem to be more suitable for treatment of patients with MRCC than 13-cRA.

PMID- 15263794
TI  - Does radical nephrectomy with immunochemotherapy have any superiority over
      embolization alone in metastatic renal cell carcinoma? A preliminary report.
AB  - INTRODUCTION: We evaluated the results and effects of radical nephrectomy
      followed by immunochemotherapy and embolization alone on the survival of patients
      with metastatic renal cell carcinoma. PATIENTS AND METHODS: The study included 20
      patients with histologically confirmed renal cell carcinoma. Ten patients were in
      the combined therapy group and the other 10 patients who were unable to undergo
      nephrectomy because of poor performance status or unresectable tumor were in the
      embolization group. Radical nephrectomy was performed on patients with good
      performance status (WHO criteria 0-1). Immunochemotherapy (interferon alpha 2a
      and 5-fluorouracil) was started within 1 month after surgery. A dose of 9 x 10(6)
      U/day interferon alpha 2a was subcutaneously administered 3 times a week. A dose
      of 750 mg/m2 5-fluorouracil was administered intravenously during 4 h in the
      first 5 days of treatment. 5-Fluorouracil therapy was converted to weekly
      intervals after the first 12 days. Combined therapy was continued for 3 months.
      Ethanol was used for transarterial embolization. The main renal arteries and
      parasitic arteries of the tumor were embolized. RESULTS: There were no
      significant differences in age distribution, sex, affected side, tumor size and T
      stage between the groups. After completion of the combined therapy, 6 patients
      showed progression at the first control. Only 1 patient (10 %) had stable disease
      throughout the 10 months after combined therapy. One patient died of myocardial
      infarction on the 4th day in the embolization group. While progressive disease
      within the first 3 months was detected in 6 patients, the other 3 patients (30%)
      had stable disease for 14, 17 and 55 months, respectively. There was no complete
      response in any group and no patient was alive (died of renal cell carcinoma) at
      the time of the analysis of the study data. Whereas the median survival time was
      11 months (1-80) (mean +/- SE: 22.2 +/- 9.1) in the combined group, this time was
      a median of 1 month (1-74) (mean +/- SE: 17.5 +/- 8.6) in the embolization group.
      There was no statistically significant difference in survival time between the
      groups (p > 0.05). CONCLUSION: In this preliminary report, the clinical findings
      in embolization-group patients were definitively worse than the nephrectomy plus
      immunochemotherapy-group patients. In spite of these differences, combination
      therapy using radical nephrectomy and immunochemotherapy could not show
      superiority to embolization alone, especially in terms of survival time.

PMID- 15263795
TI  - Investigation on the histopathological effects of thyroidectomy on the
      seminiferous tubules of immature and adult rats.
AB  - INTRODUCTION: This study aimed to investigate the histopathological effects of
      thyroidectomy on both immature and adult rat testes. MATERIALS AND METHODS: Male
      albino Wistar rats, 4 weeks old and weighing between 45 and 55 g, were used for
      this study. The experimental groups were as follows: 2-week control group (group
      I); 2-week thyroidectomy group (group II); 4-week control group (group III); 4
      week thyroidectomy group (group IV); 6-week control group (group V), and 6-week
      thyroidectomy group (group VI). The control groups included both sham-operated
      and untreated rats. In groups II, IV and VI, total thyroidectomy was performed
      under ether anesthesia in all rats at 4 weeks of age. The rats were killed in the
      2nd, 4th and 6th weeks, respectively, following the thyroidectomy. The testes of
      each animal were evaluated histologically. RESULTS: In group II, spermatogenesis
      progressed to meiosis but round spermatids were found to be decreased and
      pachytene spermatocytes were observed to be increased when compared to group I.
      Giant pachytene spermatocytes were seen. There were also many degenerated cells
      of intermediate origin in the seminiferous epithelium. In groups IV and VI,
      spermatogonia and primary spermatocytes were normal in appearance, but there was
      widespread degeneration of the other spermatogenic cells. In addition, some
      closed lumina covered by degenerated and dead cells were observed. In group II,
      the mean outer diameter, luminal diameter and area occupied by seminiferous
      epithelium decreased by 19.74, 32.18, and 28.12%, respectively. In group IV,
      these data decreased by 23.9, 16.52, and 48.5%, respectively, and in group VI, by
      21.10, 19.76 and 40.29%, respectively, when compared with the control groups.
      These data were statistically significant (p < 0.001). CONCLUSIONS: Thyroid
      hormones could have a marked influence on the seminiferous tubules of both
      immature and adult rats, and their permanent lack results in a depression in
      seminiferous tubule growth as shown by the reduced outer and luminal diameters
      and area occupied by the seminiferous epithelium, which could give rise to
      degenerative changes in the spermatogenic cells of thyroidectomized rats. In
      addition, all these changes could also result from both the inability of Sertoli
      cells to support spermatogenic cells and the diminished levels of GH and FSH.

PMID- 15263796
TI  - Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors
      p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell
      cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological
      features.
AB  - INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin
      dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to
      tumour behaviour and patients' prognosis was examined in 142 urothelial cell
      carcinomas. The expression of these proteins was also analyzed along with other
      cell-cycle-related proteins such as: p53, pRb and the proliferation-associated
      indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND
      METHODS: These molecule markers were localized immunochemically using the
      monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21
      (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma.
      RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1
      immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1
      expression was correlated with tumour grade and stage as well as with the
      existence of in situ component. In addition, cyclin D1 expression was positively
      correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score.
      Focal positivity (<20% of tumour cells) or the absence of cyclin E
      immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E
      expression was correlated with tumour stage. A positive relationship between
      cyclin E expression and the two associated proliferating indices Ki-67 and PCNA,
      as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal
      positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%)
      of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and
      stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb
      expression was observed. Absence or focal immunostaining (<20% of tumour cells)
      of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression
      was correlated with tumour grade as well as with cyclins D1 and E. The prognostic
      significance of cyclins D1, E and cyclin-dependent kinase inhibitors
      p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression
      with both univariate (log rank test) and multivariate (Cox regression) methods of
      analysis showed no statistically significance differences. CONCLUSION: These
      findings suggest that the level of the cell cycle regulators studied does not
      seem to have a clinical value in terms of predicting the risk of early recurrence
      and progression. In addition the interrelationship probably means their
      contribution to the regulation of cell growth through different pathways in
      bladder carcinogenesis.

PMID- 15263797
TI  - Acetylcholine release from urinary bladder smooth muscles of non-insulin
      dependent diabetic rats.
AB  - INTRODUCTION: To investigate the mechanism of voiding dysfunction in non-insulin
      dependent diabetes mellitus, we attempted to measure the acetylcholine (ACh)
      release using an in vivo microdialysis technique and measuring the detrusor
      pressure after electrical field stimulation (EFS) of the pelvic nerve. MATERIALS
      AND METHODS: Eight- and 32-week-old female Goto-Kakizaki (GK) rats (non-insulin
      dependent diabetes mellitus model) and age-matched female Wistar rats (controls)
      were used in this study. The pelvic nerve was exposed on a bipolar platinum
      electrode to EFS, and a cannula was inserted into the bladder to measure the
      detrusor pressure. The microdialysis probe was inserted into the bladder wall and
      was connected to a microinfusion syringe pump. Dialysate was constantly perfused,
      collected in a microtube, and then injected into the ACh assay system.
      Histological examinations were performed by staining with hematoxylin and eosin
      and S-100 immunohistochemical staining in bladder preparations of both GK and
      control rats. RESULTS: In 8-week-old rats, both detrusor pressures and amounts of
      ACh release of GK rats were not significantly different from those of control
      rats. In 32-week-old rats, both detrusor pressures and ACh releases were only
      significantly increased at 5 and 10 Hz of EFS. In the histological study, the
      number of nerve fibers or bundles of 32-week-old GK rats was significantly
      decreased as compared with control rats. CONCLUSION: The present data suggest
      that the decrease in EFS-induced ACh release in GK rats, which may be caused by
      the decreased number of nerve fibers, may contribute to the decrease in bladder
      contractions.

PMID- 15263798
TI  - Mixed germ cell tumor after bilateral orchidopexy in persistent Mullerian duct
      syndrome with transverse testicular ectopia.
AB  - The persistent mullerian duct syndrome is characterized by the retention of
      mullerian derivatives (fallopian tubes, uterus) in patients otherwise normally
      virilized, usually with cryptorchidism or an inguinal hernia. Very rarely, this
      syndrome is associated with transverse testicular ectopia, which designates the
      condition when both testes descend through the same inguinal canal into the same
      scrotal sac. We report on a patient with both conditions, who had T1N2M0 scrotal
      mixed germ cell tumor of the testis (teratoma and embryonal carcinoma), 18 years
      after bilateral orchidopexy. The literature concerning this uncommon association
      is reviewed.

PMID- 15263799
TI  - Late recurrence of clinical stage I seminoma of the testis after 12 years despite
      adjuvant infradiaphragmatic irradiation.
AB  - A patient treated with prophylactic infradiaphragmatic radiation therapy for
      clinical stage I left testicular pure seminoma developed a large mass of the
      chest wall 12 years after primary treatment. An incisional biopsy confirmed pure
      seminoma. After chemotherapy, surgical removal of the residual mass and second
      line chemoradiation therapy for persistent seminoma, the patient had a vertebral
      relapse. He died of progression 24 months after the first relapse despite further
      therapy.

PMID- 15263800
TI  - Condylomata acuminata of the neovagina in a HIV-seropositive male-to-female
      transsexual.
AB  - We present an unusual case of condylomata acuminata arising in the transplanted
      skin of a neovagina in a male-to-female transsexual. The neovagina had been
      constructed using a penile and a scrotal skin flap. Resection of the larger
      condylomata was performed; then all visible lesions were ablated by
      electrovaporization. Microsocpic examination and DNA hybridization revealed
      condylomata acuminata due to human papillomavirus type 16, 31, and 33 infection.

PMID- 15263801
TI  - Renal metastasis from primary hepatocellular carcinoma. A case report and review
      of the literature.
AB  - Secondary malignant tumors of the kidney are uncommon. These secondary tumors are
      usually the result of hematogenous spread from solid or hematologic malignancies.
      These tumors are almost always discovered at autopsy, with only 40 cases
      diagnosed prior to death reported in the literature. Primary tumors of the lung,
      breast and gastrointestinal tract are the most common sources of renal
      metastases. The occurrence of a renal secondary from a primary hepatocellular
      carcinoma is the subject of this presentation. To the best of our knowledge, such
      an occurrence has not been reported previously.

PMID- 15263802
TI  - Primary retroperitoneal hydatid cyst with unusual clinical manifestation.
AB  - Although hydatid disease may affect any organ of the body, there are only a
      limited number of cases where the primary lesion is in the retroperitoneal
      region. Since the clinical and laboratory findings are nonspecific, the correct
      preoperative diagnosis may be difficult. A primary retroperitoneal hydatid cyst
      that was given a preoperative diagnosis of adrenal mass and treated by
      adrenalectomy and partial nephrectomy is presented and discussed with the
      relevant literature.

PMID- 15263803
TI  - Significance of Hardy-Weinberg equilibrium in case control.

PMID- 15263805
TI  - Upregulated CD44v9 expression inhibits the invasion of oral squamous cell
      carcinoma cells.
AB  - OBJECTIVES: CD44 is one of the cell surface molecules that play an important role
      in cancer metastasis. In oral squamous cell carcinoma (OSCC), the downregulation
      of CD44v9 has been shown to be associated with tumor metastasis. We found that
      treatment with an anti-CD44v9 antibody enhanced the invasive potential of OSCC
      cell lines. Based on previous studies and our results, reduced expression of
      CD44v9 may be correlated with an increased invasive potential, i.e. the
      overexpression of CD44v9 may inhibit the invasive activity of OSCC cells.
      METHODS: To study this correlation, we transfected the CD44v9 gene into HSC-4
      cells with low CD44v9 expression and examined their invasive potential using the
      cell culture invasion assay and a three-dimensional culture invasion assay.
      RESULTS: Overexpression of CD44v9 resulted in a downregulation of the invasive
      potential of HSC-4 cells. Moreover, CD44v9-transfected cells did not invade
      reorganized stroma, while parent HSC-4 cells exhibited diffuse invasion into
      reorganized stroma by the three-dimensional culture invasion assay. CONCLUSIONS:
      Overall, these findings suggest that the inhibition of the invasive potential by
      upregulation of CD44v9 expression may be due to enhanced cell-cell adhesion. In
      our opinion, the upregulation of CD44v9 may be a target for future cancer
      treatment.

PMID- 15263806
TI  - Expression of PRL-3 phosphatase in human gastric carcinomas: close correlation
      with invasion and metastasis.
AB  - OBJECTIVE: High expression of PRL-3, a protein tyrosine phosphatase, has been
      reported to be associated with metastasis of colorectal carcinoma. The aim of
      this study is to investigate the significance of PRL-3 expression in tumor
      progression and metastasis of gastric carcinoma. METHODS: The levels of PRL-3
      mRNA expression in 8 gastric cancer cell lines were examined by RT-PCR. Ninety
      four human gastric carcinomas and 54 matched lymph node metastases were employed
      in this study. The expression of PRL-3 was detected by immunohistochemistry and
      the relationship with clinicopathological parameters was analyzed. RESULTS: The
      expression of PRL-3 mRNA was clearly detected in 7 of 8 gastric cancer cell lines
      (87.5%) by RT-PCR. In tumor samples, PRL-3 expression was detected in 68% of
      primary gastric carcinoma (with nodal metastasis 81.5%, without nodal metastasis
      50%; p = 0.004). The incidence of PRL-3 expression in lymph node metastasis was
      significantly higher than that in primary gastric cancers (p < 0.001). Moreover,
      PRL-3 expression was closely associated with lymphatic invasion (p = 0.002),
      extent of lymph node metastasis (p = 0.002) and tumor stage (p = 0.045).
      CONCLUSIONS: These results strongly suggest that PRL-3 expression may play a
      significant role in invasion and metastasis of gastric carcinoma. PRL-3 might be
      a novel molecular marker for aggressive gastric cancer.

PMID- 15263807
TI  - Expression of splice variants of the human ADAM15 gene and strong interaction
      between the cytoplasmic domain of one variant and Src family proteins Lck and
      Hck.
AB  - OBJECTIVE: The aim of the present study was to show variant species of ADAM15 and
      unique Src homology 3 (SH3)-binding motifs, which strongly bound Src family
      proteins compared with ADAM15. METHODS AND RESULTS: RT-PCR using primers for the
      cytoplasmic domain revealed the presence of different species, designated
      ADAM15v1 and ADAM15v2, which had characteristic SH3-binding class I and class II
      motifs. The mRNA of ADAM15v1 and ADAM15v2 was mainly found in peripheral blood
      mononuclear cells, T lymphocytes and monocytic cell lines. ADAM15v2 protein
      interacted more strongly with the Src family proteins Lck and Hck than did ADAM15
      protein, as examined by pull-down analysis and immunoprecipitation followed by
      immunoblot analysis. The binding with Lck and Hck was enhanced by the
      phosphorylation of ADAM15v2 protein. CONCLUSIONS: These results suggest that the
      cytoplasmic domain of ADAM15v2 strongly interacts with Lck and Hck and regulates
      leukocyte function.

PMID- 15263808
TI  - MCM2 and Ki-67 expression in human lung adenocarcinoma: prognostic implications.
AB  - OBJECTIVE: The expressions of minichromosome maintenance protein 2 (MCM2), Ki-67,
      and p53 were examined to analyze their pathobiological significance in human lung
      adenocarcinomas. METHODS: We performed Western blot analysis in six human lung
      adenocarcinoma cell lines and immunohistochemistry in 145 surgically removed
      adenocarcinomas to examine the MCM2 expression. Labeling indices (LIs; %) of
      MCM2, Ki-67, and p53 in the tumor cells were compared with clinicopathological
      profiles and overall survival rates. RESULTS: MCM2 protein was detected in all
      cell lines examined, with specific bands. MCM2 LIs were significantly correlated
      with sex, histological type, differentiation, pathological stage, and LIs of Ki
      67 and p53 (p < 0.05). Significantly higher LIs of MCM2 and Ki-67 were noted in
      the 122 non-pure bronchioloalveolar carcinomas than in the 23 pure
      bronchioloalveolar carcinomas (p < 0.01), and the prognosis was poorer in the
      former than in the latter (p < 0.01). Sex, pathological stage, and high LIs of
      MCM2 and/or Ki-67 were independent prognostic factors (p < 0.05). CONCLUSION:
      High LIs of MCM2 and/or Ki-67 suggest a poor prognosis in patients with lung
      adenocarcinoma (non-pure bronchioloalveolar carcinoma).

PMID- 15263809
TI  - Molecular pathological analysis of mucinous adenocarcinomas of the stomach.
AB  - OBJECTIVE: Mucinous adenocarcinomas (MACs) of the stomach usually show an
      invasive expansive growth and a poor prognosis. We examined the possibility of
      molecular pathological subtyping of MACs of the stomach. METHODS: Forty-one
      formalin-fixed and paraffin-embedded MAC specimens of the stomach were analyzed.
      Mucin subtypes (MUC2, CD10, HGM, M-GGMC-1) and expression levels of hMLH1, p53
      and Ki-67 were analyzed by immunohistochemistry as well as genetic alterations in
      the p53 gene and microsatellite instability (MSI). RESULTS: According to both MSI
      and p53 status, these tumors were subclassified into three groups: the mutator
      type tumors, the suppressor/p53-type tumors and the unclassified tumors. The
      mutator-type tumors demonstrated lower p53 expression and had lower proliferative
      activity than the suppressor/p53-type tumors, whereas most of the suppressor/p53
      type tumors expressed CD10. However, there was no significant difference between
      the mutator- and suppressor/p53-type tumors in clinicopathological parameters
      including the patients' outcome. CONCLUSION: Our results indicate that MACs of
      the stomach are composed of at least three subtypes according to the molecular
      pathological background for their carcinogenesis. Further study of carcinomas
      with detailed morphological and biological phenotyping of each subtype may
      provide useful information for better clinical management.

PMID- 15263810
TI  - Orexins and their receptors in the human retina.
AB  - OBJECTIVES: Orexins A and B are neuropeptides involved in the regulation of
      feeding behavior, energy homeostasis and arousal. In the human retina, however,
      immunohistochemical localization of orexins and their receptors, OX-R1 and OX-R2,
      has not been ascertained. METHODS: We localized orexins A and B, OX-R1 and OX-R2
      in the human retina using immunohistochemistry. Retinae from 2 Alzheimer's
      disease (AD) patients provided preliminary evidence for possible orexin
      alterations. RESULTS: Orexin A, orexin B and OX-R1 were localized in ganglion and
      amacrine cells, cellular processes in the inner and outer plexiform layer and in
      the inner segments of photoreceptor cells. There was no OX-R2 immunoreactivity in
      the retina. The staining intensity for both orexins was decreased in the AD
      patients. CONCLUSION: This immunohistochemical study provides the first evidence
      for the distribution of orexin A, orexin B and OX-R1 in the human retina. The
      localization pattern suggests a modulatory role for orexins in the interactions
      of those retinal cells which transmit light information to the suprachiasmatic
      nuclei, and thus may be involved in circadian rhythm entrainment.

PMID- 15263811
TI  - High apoptotic index correlates to p21 and p27 expression indicating a favorable
      outcome of primary breast cancer patients, but lacking prognostic significance in
      multivariate analysis.
AB  - This study was performed in order to investigate the role of the apoptotic index
      (AI) as a prediction parameter for the prognosis of patients with primary breast
      cancer. AI was determined by DNA fragmentation on 298 primary breast cancer
      samples and compared to clinically established breast cancer parameters.
      Additionally, we determined the expression of functional parameters including
      proliferating cell nuclear antigen, p21waf and p27kip by immunohistochemistry.
      The mean AI was found to be 11.9% (range, 0-90%). 189 tumors (63.4%) were
      negative for apoptosis, while 109 tissue samples (36.6%) were apoptotic with >5%
      positive cells. Using univariate analysis (chi2 test), the AI did not show any
      significant correlation to one of the established prognostic parameters of
      primary breast cancer (p > 0.05). In contrast, we found a significant positive
      correlation to the expression of the cell cycle inhibitors p21waf (p = 0.04) and
      p27kip (p = 0.024). During the clinical follow-up (median observation time for
      disease-free survival 87 months), several clinically established prognostic
      parameters including menopausal status, nodal status, tumor size, tumor grade,
      and hormone receptor expression could be confirmed and were analyzed with respect
      to the AI in the tumor. Furthermore, AI displayed a significant positive
      correlation to disease-free survival using Kaplan-Meier survival analysis (log
      rank test, p = 0.04). However, AI lost its prognostic significance in
      multivariate analysis based on the Cox proportional hazard model (relative risk
      0.8, confidence interval 0.52-1.33, p = 0.44). Our data indicate that high
      apoptotic rates in cancer tissues are indicative of a favorable patient outcome.
      However, the AI was not an independent factor. The study provides indirect
      evidence that this process may involve cell cycle inhibitors physiologically.

PMID- 15263812
TI  - Alterations in the levels of metallothionein and metals in the liver, and unique
      serum liver enzyme response in metallothionein knock-out mice after burn injury.
AB  - OBJECTIVES: Metallothionein (MT) is a small cysteine-rich protein that sequesters
      and distributes metal ions. Its overexpression stimulates cell proliferation and
      inhibits apoptosis. We investigated the effects of burn injury on MT expression
      and metal localization. We also sought to determine roles of MT in the
      pathophysiologic alterations in the liver after injury. METHODS: Mice (C57BLKS/J,
      MT-I/II knock-out, KO, and wild-type control mice) were subjected to an 18% burn.
      Liver tissues harvested after injury were analyzed for the MT expression and the
      levels of zinc, copper, manganese, and iron. Levels of alanine aminotransferase,
      aspartate aminotransferase, and alkaline phosphatase were measured in serum
      samples from MT-I/MT-II KO mice and controls after injury. RESULTS: Transient
      induction of MT-I and MT-II mRNAs was observed 3-6 h after injury, while MT-I/MT
      II protein peaked on day 1. The induction was localized to hepatocytic nuclei.
      The intrahepatic levels of zinc, copper, and iron were transiently elevated on
      day 1, when a downregulation of manganese was evident. Interestingly, only the
      serum levels of aspartate aminotransferase were significantly augmented in MT
      I/MT-II KO mice compared to controls after injury. CONCLUSIONS: These data
      suggest that MT and metals may participate in the pathogenesis of the liver after
      burn injury.

PMID- 15263813
TI  - Baculovirus late expression factors.
AB  - Autographa californica nuclear polyhedrosis virus, or AcMNPV, is the type member
      of the baculoviruses, a family of double-stranded DNA viruses with large circular
      genomes. The successive and concomitant expression of an assortment of early,
      late and very late genes is instrumental for successful baculovirus infection,
      and requires a switch from early dependence on a host cell-derived polymerase II
      to a novel virus-encoded RNA polymerase that is required for transcription later
      on in infection. A series of repetitive and highly conserved sequences known as
      homologous regions, or hrs, function both as origins of DNA replication as well
      as transcriptional enhancers of late gene expression. An array of AcMNPV genes
      produced early on in infection, known as late expression factors, or LEFs, are
      essential for both replication and late gene expression. In this review, an
      overview of baculovirus LEFs and their roles in viral replication and late gene
      expression is presented. The role of LEFs in determining baculovirus host range
      is described. Finally, we compare baculovirus replication and transcription
      machinery with other viral systems.

PMID- 15263814
TI  - Sequence analyses of cyanobacterial bicarbonate transporters and their
      homologues.
AB  - The primary HCO3- uptake system in the cyanobacterium Synecocystis is the Na+
      dependent transporter SbtA. SbtA and its homologues were identified and shown to
      display a common topology of ten transmembrane segments (TMSs). These proved to
      have arisen by an intragenic duplication event from an ancestral gene encoding a
      five TMS protein product. A region of SbtA shows sufficient similarity to 10 TMS
      ABC-type integral membrane transport proteins to suggest a common origin.
      Phylogenetic analyses of the SbtA family revealed two clusters of cyanobacterial
      homologues with all non-cyanobacterial family members outside of these two
      clusters. The tree topology suggests that SbtA family members display multiple
      transport functions.

PMID- 15263815
TI  - Expression and purification of heterologous proteins in plant tissue using a
      geminivirus vector system.
AB  - In the past, plant molecular biologists have relied on Escherichia coli,
      baculovirus and other expression systems to produce plant proteins to quantities
      sufficient for biochemical analysis. However, such expression systems often
      result in the production of proteins which possess improper posttranslational
      modifications. Here, we present a plant virus-based expression system superior to
      those currently available. We demonstrate that bean yellow dwarf geminivirus
      (BeYDV) replicates and expresses foreign proteins at high levels in tobacco,
      Arabidopsis, and other dicotyledonous plants, making it more universal than plant
      RNA viruses with restricted host ranges which are currently used as expression
      systems. The DNA-based nature of the BeYDV genome renders it stable for the
      incorporation of large plant open reading frames, and gives it an advantage over
      other plant virus-based expression systems which possess insert size
      restrictions. Using this expression system, the rapid accumulation of a novel
      Arabidopsis-derived mitogen-activated protein kinase to levels sufficient for
      standard biochemical analysis is demonstrated.

PMID- 15263816
TI  - Four promoters subject to regulation by ExoR and PhoB direct transcription of the
      Sinorhizobium melilotiexoYFQ operon involved in the biosynthesis of
      succinoglycan.
AB  - Succinoglycan (EPS I), the main acidic exopolysaccharide of Sinorhizobium
      meliloti, is required for the initiation and elongation of infection threads
      during nodulation of the host plant alfalfa. The gene products of the exoYFQ
      operon are involved in the first step of succinoglycan biosynthesis as well as in
      the polymerisation of subunits to the high-molecular-mass form of this
      exopolysaccharide. One promoter region that directs transcription of exoX and two
      promoter regions that drive transcription of exoY were mapped in the exoX-exoY
      intergenic region. The distal exoY promoter region containing three putative -10
      promoter elements was active under standard growth conditions and was subject to
      ExoR-dependent regulation. Although this promoter region was stimulated in a phoB
      mutant, no PHO box-like sequences were found, suggesting an indirect regulatory
      effect of PhoB. The proximal promoter contains a PHO box-like sequence in the
      putative -35 region and was affected by low and high phosphate concentrations
      dependent on PhoB. In the case of deleted upstream regions, this promoter was
      also controlled by ExoR. An additional promoter displaying activity in exoR, mucR
      and phoB mutants under standard conditions was identified upstream of exoF. The
      putative -35 promoter element of this promoter is covered by a second PHO box
      like sequence.

PMID- 15263817
TI  - Probing for pH-regulated genes in Sinorhizobium medicae using transcriptional
      analysis.
AB  - The low pH sensitivity of Sinorhizobium species is one of the major causes of
      reduced productivity of Medicago species (such as lucerne) sown in acidic soils.
      To investigate the pH response of an acid-tolerant Sinorhizobium medicae strain,
      a pool of random promoter fusions to gusA was created using minitransposon
      insertional mutagenesis. Acid-activated expression was identified in 11 mutants;
      rhizobial DNA flanking insertions in 10 mutants could be cloned and the DNA
      sequences obtained were used to interrogate the genome database of Sinorhizobium
      meliloti strain 1021. Acid activated expression was detected for fixNO, kdpC,
      lpiA, and phrR and for genes encoding a putative lipoprotein, two ABC-transporter
      components, a putative DNA ligase and a MPA1-family protein. These findings
      implicate cytochrome synthesis, potassium ion cycling, lipid biosynthesis and
      transport processes as key components of pH response in S. medicae.

PMID- 15263818
TI  - Probing for pH-regulated proteins in Sinorhizobium medicae using proteomic
      analysis.
AB  - To elucidate the mechanisms of pH response in an acid-tolerant Sinorhizobium
      medicae strain we have identified acid-activated gene transcription and now
      complement this approach by using a proteomic analysis to identify the changes
      that occur following exposure to acidity. Protein profiles of persistently or
      transiently acid-stressed S. medicae cells were compared to those grown in pH
      neutral, buffered media. Fifty pH-regulated proteins were identified; N-terminal
      sequences for 15 of these were obtained using the Edman degradation. Transient
      acid exposure downregulated GlnA and GlnK and upregulated a hypothetical protein.
      Continuing acid exposure downregulated ClpP, an ABC transporter, a hypothetical
      protein, a lipoprotein, the Trp-like repressor WrbA1 and upregulated DegP,
      fructose bisphosphate aldolase, GroES, malate dehydrogenase and two hypothetical
      proteins. These findings implicate proteolytic, chaperone and transport processes
      as key components of pH response in S. medicae.

PMID- 15263819
TI  - Composition and activity of the Rhodobacter capsulatus degradosome vary under
      different oxygen concentrations.
AB  - The influence of changes in temperature or oxygen tension during growth of
      Rhodobacter capsulatus on the composition and activity of the degradosome, an RNA
      processing protein complex, was investigated. Only minor differences in the
      amount of specific proteins of the complex were observed after a decrease or
      increase of the temperature, but dramatic variations were detectable during
      growth at different oxygen concentrations. In particular, the amount of the
      transcription factor Rho, which was previously shown to be associated with the R.
      capsulatus degradosome, was strongly increased under aerobic conditions.
      Remarkably, oxygen tension oppositely affected the levels of the two helicases
      associated with the degradosome. RNase E and the degradosome from aerobically
      grown cultures degraded a transcript which represents part of the puf operon
      encoding proteins of the photosynthetic apparatus faster than did the degradosome
      from semiaerobically grown cultures.

PMID- 15263820
TI  - Down syndrome candidate region 1,a downstream target of VEGF, participates in
      endothelial cell migration and angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is a principal stimulator of
      angiogenesis. However, the downstream targets of VEGF in endothelial cells (ECs)
      are not entirely clarified. Survey of downstream targets of VEGF in human ECs
      identified a number of genes, including Down syndrome candidate region 1 (DSCR1).
      Here, we confirmed the inducible expression of DSCR1 in ECs by Northern and
      Western blottings. Moreover, VEGF-stimulated induction of DSCR1 was blocked by
      anti-VEGF receptor-2 monoclonal antibody (mAb), or the specific calcineurin
      inhibitors cyclosporin A and FK506. The expression of DSCR1 in ECs of neovessels
      was further shown by immunohistochemical analysis. We therefore examined whether
      DSCR1 played any roles in angiogenesis. The specific downregulation of DSCR1
      expression by antisense oligonucleotide (AS-ODN) inhibited VEGF-stimulated
      migration of ECs as well as angiogenesis in vivo. AS-ODN inhibited the spreading
      of ECs on vitronectin, as well as on the immobilized anti-alphavbeta3 mAb, but
      not on anti-alphavbeta5 mAb. Moreover, AS-ODN inhibited tyrosine phosphorylation
      of focal adhesion kinase when ECs were plated on a vitronectin-coated dish.
      Immunoprecipitation followed by Western blotting showed the coimmunoprecipitation
      of DSCR1 and integrin alphavbeta3. These results suggest that DSCR1 is involved
      in angiogenesis by regulating adhesion and migration of ECs via the interaction
      with integrin alphavbeta3.

PMID- 15263821
TI  - Adult height distribution in subjects born small for gestational age.
AB  - The aim of the study was to investigate the post-natal growth of subjects born
      small for gestational age (SGA) by describing adult height distribution and by
      testing the effects of parental, neonatal and pregnancy-related parameters on the
      risk for adult short stature. The study population was made of adults selected on
      birth data from a maternity registry and born either small (SGA, n = 734, birth
      weight < 10th percentile) or appropriate for gestational age (AGA, n = 886, 25th
      < birth weight < 75th percentile) in whom anthropometric parameters were measured
      at 22 years of age. The SGA group demonstrated significantly reduced body size in
      comparison to the AGA group with a mean loss of 0.7 standard deviation (SD) in
      adult height. The frequency of adult short stature (< -2 SD) was 10.3% in the SGA
      group vs. 2.4% in the AGA group (p = 0.0001), adult height < -2.5 SD was observed
      in only 3.7% of the SGA group. Maternal (OR = 0.31 (0.16-0.62), p = 0.0001) and
      paternal (OR = 0.45 (0.31-0.67), p = 0.0001) heights and subjects birth length
      (OR = 0.78 (0.62-0.99), p = 0.04) significantly influenced the risk of adult
      short stature. In summary, post-natal growth defect remains moderate in the
      majority of subjects born SGA and < 4% only will end up with severe short stature
      requiring GH therapy according to most current recommendations. The role of
      parental height and birth length suggests that adult short stature in SGA
      subjects results at least in some cases from a familial and likely genetic growth
      disorder with antenatal onset.

PMID- 15263822
TI  - Organ procurement in experimental pancreas transplantation with minimal
      microcirculatory impairment.
AB  - BACKGROUND: Ischemia-reperfusion injury has been shown to deteriorate
      microcirculation in experimental pancreas transplantation. However, minor concern
      was taken on the impact of organ procurement in this condition. We examined the
      impact of a standardized technique of organ procurement on microcirculation and
      apoptosis in experimental pancreas transplantation. METHODS: Male Lewis rats were
      divided into three groups: sham-operated animals without dissection of the
      pancreas served as controls (n = 5); animals undergoing nearly total process of
      organ procurement with the pancreas pedunculated on the aorta and the
      hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal
      transplantation. Pancreatic grafts were preserved for 6 h in cold University of
      Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched
      controls, microcirculation was assessed by means of intravital fluorescence
      microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of
      acinar cells were detected by in situ nick end-labeling (TUNEL assay). The
      apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by
      microscopic counting of at least 50 hpf. RESULTS: Assessment of functional
      capillary density (FCD) in animals undergoing subtotal process of organ
      procurement revealed a slight non-significant decrease at 1 and 2 h compared with
      controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well
      as the apoptotic index were found slightly increased after organ procurement
      compared with controls (p > 0.05). However, after pancreas transplantation the
      apoptotic index and the LAV were significantly increased and the FCD
      significantly decreased compared with both groups of non-transplanted animals (p
      < 0.01). CONCLUSIONS: Our validated technique of organ procurement does not
      negatively impact microcirculation and apoptosis in experimental pancreas
      transplantation.

PMID- 15263823
TI  - Preservation injury of jejunal grafts and its modulation by custodiol and
      university of wisconsin perfusion solutions in wistar rats.
AB  - BACKGROUND: The two preservation solutions most commonly used in human
      transplantation surgery are University of Wisconsin (UW) and Custodiol (histidine
      tryptophan-ketoglutarate; HTK). The aim of our study was to compare the
      protective effect of UW and HTK solutions on preservation-induced injury of
      jejunal grafts, as evaluated by the histological changes (semiquantitative
      method) and small bowel mucosal serotonin levels (as a possible new quantitative
      method). METHODS: Male Wistar rats (n = 50) weighing 316 +/- 52 g were divided
      into two main groups according to which preservation solution was used, i.e. UW
      (n = 25) or HTK (n = 25), and each of these groups was divided into five
      subgroups according to cold ischemic time (0, 1, 6, 9 and 12 h). Jejunal mucosa
      biopsy specimens were obtained to determine the serotonin concentration in mucosa
      and for standard light histology. To grade histological changes in mucosa, Park's
      small bowel injury grading system was used. RESULTS: Histological examination
      revealed that injury increased with cold ischemic time in the UW as well as in
      the HTK group, and there were no significant differences in injury between the
      two groups, except for the 6-hour cold ischemic period (p < 0.05), when HTK
      preserved grafts showed a lower degree of injury (0.97 +/- 0.41) compared with UW
      preserved grafts (1.25 +/- 0.39). The mucosal serotonin concentration decreased
      with cold ischemic time in both groups, and there were significant differences (p
      < 0.05) in concentrations between the groups after 9 and 12 h of cold ischemia. A
      significantly higher concentration was measured in grafts preserved in UW
      solution at these time points. CONCLUSION: The concentration of mucosal serotonin
      in rat small bowel grafts preserved for 9 and 12 h in UW preservation solution
      was significantly higher than that in HTK solution. These findings indicate a
      better protective effect of UW solution on small bowel injury after 9 h of cold
      ischemia.

PMID- 15263824
TI  - Can we continue research in splenectomized dogs? Mycoplasma haemocanis: old
      problem--new insight.
AB  - We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs,
      which has been reported previously, yet, never before in Europe. Outbreak of the
      disease was triggered by a splenectomy intended to prepare the dogs for a
      hemorrhagic shock study. The clinical course of the dogs was dramatic including
      anorexia and hemolytic anemia. Treatment included allogeneic transfusion,
      prednisone, and oxytetracycline. Systematic follow-up (n = 12, blood smears,
      antibody testing and specific polymerase chain reaction) gives clear evidence
      that persistent eradication of M. haemocanis is unlikely. We, therefore, had to
      abandon the intended shock study. In the absence of effective surveillance and
      screening for M. haemocanis, the question arises whether it is prudent to
      continue shock research in splenectomized dogs.

PMID- 15263825
TI  - Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion
      injury.
AB  - The aim of the present study was to determine the effects of erdosteine, a new
      antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil
      infiltration, and antioxidant enzyme activities in a rat model of renal ischemia
      reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham
      operation, I/R, and I/R plus erdosteine groups. After the experimental procedure,
      rats were sacrificed and kidneys were removed and prepared for malondialdehyde
      (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and
      superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were
      significantly increased in the I/R group. On the other hand, SOD and CAT
      activities were found to be decreased in the I/R group compared to the sham
      group. Pretreatment with erdosteine significantly diminished tissue MDA level,
      MPO and XO activities. Our data support a role for erdosteine in attenuation in
      renal damage after I/R injury of the kidney, in part at least by inhibition of
      neutrophil sequestration and XO activity.

PMID- 15263826
TI  - Indocyanine green fluorescence measurement of intestinal transit and gut
      perfusion after intestinal manipulation.
AB  - BACKGROUND AND AIMS: Postoperative ileus is a common and poorly understood
      problem of abdominal surgery. The aim of this study was to measure postoperative
      intestinal transit and to evaluate bowel wall perfusion by a novel in vivo
      indocyanine green (ICG)-fluorescence measurement following intestinal
      manipulation (IM). METHODS: Rats underwent a simple intestinal manipulation.
      Myeloperoxidase-positive cells in the muscularis were stained with the Hanker
      Yates reaction and quantified histochemically. Bowel wall perfusion was
      determined directly and 24 h postoperatively using a laser-fluorescence detection
      unit. Intestinal transit was visualized 24 h after IM. RESULTS: IM resulted in a
      massive infiltration (155-fold) of neutrophils into the intestinal muscularis 24
      h postoperatively. Bowel wall perfusion significantly decreased directly and 24 h
      following surgery (29 and 59%, respectively). Gastrointestinal transit was
      similarly impaired and showed a reduction to 40% of the control values 24 h after
      IM. CONCLUSION: IM of the rat small intestine caused an impairment in bowel wall
      perfusion and microcirculation and a significant decrease in gastrointestinal
      transit. The ICG fluorescence measurement using the described system proved to be
      a simple and reliable method to evaluate intestinal transit and bowel wall
      microcirculation in vivo.

PMID- 15263827
TI  - Exogenous and endogenous nitric oxide donors improve post-ischemic tissue
      oxygenation in early pancreatic ischemia/reperfusion injury in the rat.
AB  - INTRODUCTION: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of
      nitric oxide (NO) is not completely understood. Using a rat model of normothermic
      in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic
      tissue oxygenation and tissue damage was investigated. METHODS: IR was induced by
      2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on
      the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a
      sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without
      ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a
      pO2-sensitive Clark-type electrode. Histological investigation was performed
      following a semiquantitative score (edema, vacuolization, PMN infiltration,
      necrosis). Plasma lipase was another marker of organ damage. RESULTS: The
      administration of L-arginine and sodium nitroprusside caused a significant
      amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p
      < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05).
      After reperfusion, plasma lipase in the L-arginine-treated animals was
      significantly lower compared to IR and sodium nitroprusside (p < 0.05).
      CONCLUSIONS: The administration of both endogenous and exogenous NO donors is
      protective in IRI of the rat pancreas which can be seen by an improvement in post
      ischemic tissue oxygenation which indicates better nutritive tissue perfusion,
      amelioration of the histological tissue injury and, in L-arginine animals, lower
      lipase levels. NO donors could be useful in the prevention and reduction of the
      pancreatic IRI.

PMID- 15263828
TI  - Effects of obstructive jaundice on the peripheral nerve: an ultrastructural study
      in rats.
AB  - Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated
      with peripheral neuropathy in several clinical studies. The study evaluated the
      effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group,
      jaundice was created by ligation of common bile duct in Wistar-Albino rats. In
      the sham-operated control group the same procedure was performed without ligation
      of the bile duct. On day 7, all rats were re-operated and sciatic nerves were
      explored to harvest 2-cm-long nerve segments for quantitative and qualitative
      histopathological analysis by light and electron microscopy. Bilirubin was
      measured on serum samples. Bilirubin levels were significantly higher in
      jaundiced rats compared with that of controls (8.46 +/- 0.45 vs. 0.80 +/- 0.14
      mmol/l, means +/- SD, p < 0.01). Control nerves did not show anything other than
      the normal histology. In the OJ group, degenerative changes such as
      irregularities, thinning, ruffling and invaginations, irregularshaped bodies,
      vacuolizations and focal segmental demyelination were observed in the myelin
      sheath. Myelin clusters were noted in the axoplasm. A varying degree of swelling
      was noted in the nucleus and cytoplasm of the Schwann cells. Morphometric
      analysis of specimens obtained from sciatic nerves showed that myelin injury
      (370.9 +/- 51.3 vs. 11.6 +/- 0.5 axons), axonal edema (142.1 +/- 24.2 vs. 10.6 +/
      0.5 edematous axons) and Schwann cell degeneration (50.3 +/- 11.6 vs. 3.2 +/-
      0.2 Schwann cells) was significantly higher in the jaundiced rats than in the
      control group (p < 0.01). The ultrastructural alterations spotted in the rat
      peripheral nerve were attributed to hyperbilirubinemia and increased
      concentrations of several neurotoxic substances released from the Kupffer cells
      in OJ. Neuropathy in jaundiced patients seems to result from accompanying
      degenerative changes in the peripheral nervous system. However, the exact nature
      and initiating factors of this nerve injury remains to be unveiled.

PMID- 15263829
TI  - Skin preservation at a supraphysiologic temperature and induction of epithelial
      cysts by subcutaneous grafting: attempts to simplify evaluation of storage media
      and of graft viability.
AB  - This pilot study used a new experimental rat model designed to explore whether in
      depth investigation of the following two questions would be reasonable: (1) Can
      skin storage media be faster evaluated by storing skin at a supraphysiologic
      temperature, and (2) can evaluation of skin graft viability be facilitated by
      subcutaneous grafting leading to production of epithelial cysts from the viable
      portions of the grafts? The experiment involved skin storage at 47.3 degrees C in
      saline and in 10% Dextran 40 solution for periods ranging from 0 to 18 min,
      followed by subcutaneous grafting. The surface area of the resultant epithelial
      cysts and the cyst-to-graft ratio inversely correlated with storage time, which
      is in accordance with a well-established analogous relationship involving the
      rate of graft 'take'. The skin tended to remain viable longer in Dextran 40
      solution, which is consistent with previous studies of low temperature storage
      demonstrating superiority of high-molecular-weight solutions. The results warrant
      further investigation of the above issues.

PMID- 15263830
TI  - Implantation of novel small-diameter polyurethane vascular prostheses interposed
      in canine femoral and carotid arteries.
AB  - OBJECTIVES: The performance of small-diameter (3-5-mm) vascular grafts still
      poses a challenge in the field of vascular surgery. We present here our
      preliminary experience with implanting unique small-sized polycarbonate urethane
      vascular grafts in 7 dogs. MATERIAL AND METHODS: Each animal was implanted with 4
      interposition grafts, 2 femoral and 2 carotid. No anti-thrombotic medication was
      administered. Doppler sonography was performed at 3-month intervals to examine
      for patency and flow characteristics. Animals were sacrificed electively at 3, 6
      and 12 months. RESULTS: At 3 months, all grafts were patent. After 6 months, 3
      grafts occluded and at 1 year a further 6 grafts occluded. Hence 9 of 28 grafts
      occluded (67.9% patency). During the study, no correlation could be established
      between flow velocity or resistance index and occlusion. Histopathology showed
      intimal hyperplasia to be the cause of occlusion. CONCLUSIONS: Compared to
      literature data on small-diameter grafts in the same position, ADIAM's
      Biomechanical grafts performed clearly better. Compliance data suggest a
      correlation between elastic compliance and patency.

PMID- 15263831
TI  - E-PASS (The Estimation of Physiologic Ability and Surgical Stress) scoring system
      helps the prediction of postoperative morbidity and mortality in thoracic
      surgery.
AB  - OBJECTIVE: When a new scoring system, 'E-PASS', standing for the Estimation of
      Physiologic Ability and Surgical Stress that predicts the postoperative surgical
      risk by quantification of the patient's reserve and surgical stress applied to a
      population of general thoracic surgery patients, it should be investigated if
      this system could help us or not. METHODS: The comprehensive risk score (CRS) of
      the E-PASS and the clinical course were evaluated retrospectively in 282
      consecutive patients with primary lung cancer (group A), and in 458 patients who
      underwent elective thoracic operations (group B). RESULTS: The morbidity and
      mortality rates in both group A and group B increased as the CRS increased. The
      CRS correlated significantly with the morbidity score, length of stay and cost of
      hospitalization. CONCLUSIONS: E-PASS scoring system may be useful in surgical
      decision-making and evaluating quality of care in patients who are tolerable for
      lung resection.

PMID- 15263832
TI  - Efficacy of local adrenalin injection during sacrococcygeal pilonidal sinus
      excision.
AB  - BACKGROUND: The most commonly preferred treatment method for sacrococcygeal
      pilonidal sinus disease is surgery. Peroperative and postoperative hemorrhages
      may develop frequently because of the increased vascularity of the region. The
      aim of this study was to evaluate the effects of adrenalin, a potent
      vasoconstrictor agent, on pilonidal sinus operations in comparison to a control
      group. METHODS: A prospective, randomized, double-blind, clinical study was
      designed and 51 patients with symptomatic, uncomplicated pilonidal disease were
      included (44 males and 7 females; mean age 24.5, range 16-44 years). Adrenalin
      0.1 mg with 10 ml 0.9% NaCl (1/100,000 dilution) was injected through the
      incision tracts to all layers and the base of the incision area in group 1 (n =
      21). The same process was applied to group 2 (n = 21) with 10 ml physiological
      serum solution. Then, after removal of the sinus and its tracks, a suction-type
      drain was placed in the pouch in all cases and the incision was primarily closed.
      Peroperative and postoperative hemorrhage, and operation time were accepted as
      the evaluation criteria. Cases were followed for 6 months postoperatively.
      RESULTS: The amount of peroperative hemorrhage was 6.5 +/- 3.5 ml in group 1 and
      17.5 +/- 9.5 ml in group 2 (p < 0.001). The postoperative hemorrhage was 11 +/-
      7.5 ml in group 1 and 13.5 +/- 6 ml in group 2 (p > 0.05). The operation time was
      14 +/- 5 min in group 1 and 22 +/- 8.5 min in group 2 (p < 0.05). No reactionary
      hemorrhage, hematoma or recurrence was seen during the follow-up period.
      CONCLUSIONS: Adrenalin injection is quite effective to decrease peroperative
      bleeding and operation time, but it does not decrease postoperative bleeding and
      the need for a drain.

PMID- 15263833
TI  - Effects of ibuprofen and hypoxia on neutrophil apoptosis in neonates.
AB  - BACKGROUND: Ibuprofen is a cyclooxygenase inhibitor that is effective in treating
      patent ductus arteriosus in preterm infants. However, recent trials have
      suggested that it may increase the risk of developing necrotizing enterocolitis
      and chronic lung disease. Apoptosis of neutrophils is impaired in newborns,
      leading to reduced clearance of activated cells and possibly contributing to the
      susceptibility of infants to these inflammatory diseases. OBJECTIVES: In the
      present studies, we investigated the hypothesis that ibuprofen reduces neonatal
      neutrophil apoptosis in the setting of hypoxia or lipopolysaccharide (LPS).
      METHODS: Neutrophils and peripheral blood mononuclear cells were isolated from
      adult and cord blood and cultured in the presence or absence of ibuprofen (1.5
      mM), hypoxia (<5% O2), and bacterial LPS (100 ng/ml). Apoptosis was quantified by
      measuring binding of FITC-Annexin V using flow cytometry. Cytokine concentrations
      in cell supernatants were measured by ELISA. RESULTS: After 24 h, 20% of adult
      and 14% of neonatal neutrophils were apoptotic. Apoptosis was reduced by hypoxia
      in both adult and neonatal cells. Ibuprofen further reduced neutrophil apoptosis,
      but only when the cells were cultured in the presence of mixed leukocytes. This
      suggests that the effects of ibuprofen on apoptosis are dependent on soluble
      products secreted by peripheral blood mononuclear cells. We found that production
      of tumor necrosis factor (TNF)-alpha by neonatal leukocytes was significantly
      increased by ibuprofen, and was further increased following exposure to ibuprofen
      in the presence of LPS and hypoxia. In contrast, production of macrophage
      inflammatory protein (MIP)-1alpha was not affected by treatment with ibuprofen,
      and ibuprofen blocked induction of this chemokine by LPS. CONCLUSION: We conclude
      that the net effect of ibuprofen on neutrophils is antiapoptotic, especially in
      the presence of hypoxia or LPS. This effect may be mediated, in part, by
      increased production of TNF-alpha by peripheral blood mononuclear cells. These
      data suggest that treatment of infants with ibuprofen, in the presence of
      infection and/or tissue hypoperfusion/hypoxia, may contribute to the development
      of inflammatory diseases.

PMID- 15263834
TI  - Gene profile changes after Pseudomonas aeruginosa exposure in immortalized airway
      epithelial cells.
AB  - To test the hypothesis that the excess inflammatory response in cystic fibrosis
      airway epithelial cells is the result of differential activation of genes in
      response to a laboratory strain of Pseudomonas aeruginosa (PAO1), a 48-h time
      course of genes expressed following PAO1 stimulation (10(9) CFU for 1 h) was
      studied in two pairs of airway epithelial cells: 9/HTEo- and 16HBE14o-, each with
      a matched normal and CF phenotype pair. cRNA was hybridized to Affymetrix HG
      U95Av2 chips and pairwise comparisons against zero time (no PAO1) were calculated
      for each time point. PAO1 elicited profound changes in both cell pairs: for
      9/HTEo-, 144 genes changed significantly in the normal pair, and 116 for the CF
      pair; for the 16HBE14o- pair, 57 genes changed significantly for the normal pair
      and 53 for the CF pair. Changes were much greater in the 9/HTEo- than in the
      16HBE14o- pair, but basal levels of expression of inflammatory genes are higher
      in the 16HBE14o- pair, so 16HBE14o- was used mainly to corroborate the results of
      9/HTEo-. Clustering analysis indicated that the pattern of gene expression is
      similar in the CF cells and their normal counterparts. However, there were
      substantial quantitative differences in gene expression. Thus, the difference
      between CF and normal resides in the magnitude, not the pattern, of the changes.

PMID- 15263835
TI  - Refolding strategies from inclusion bodies in a structural genomics project.
AB  - The South-Paris Yeast Structural Genomics Project aims at systematically
      expressing, purifying and determining the structure of S. cerevisiae proteins
      with no detectable homology to proteins of known structure. We brought 250 yeast
      ORFs to expression in E. coli, but 37% of them form inclusion bodies. This
      important fraction of proteins that are well expressed but lost for structural
      studies prompted us to test methodologies to recover these proteins. Three
      different strategies were explored in parallel on a set of 20 proteins: (1)
      refolding from solubilized inclusion bodies using an original and fast 96-well
      plates screening test, (2) co-expression of the targets in E. coli with DnaK-DnaJ
      GrpE and GroEL-GroES chaperones, and (3) use of the cell-free expression system.
      Most of the tested proteins (17/20) could be resolubilized at least by one
      approach, but the subsequent purification proved to be difficult for most of
      them.

PMID- 15263837
TI  - Meeting review: 2003 NIH Protein Structure Initiative Workshop in Protein
      Production and Crystallization for Structural and Functional Genomics.

PMID- 15263836
TI  - NMR for structural proteomics of Thermotoga maritima: screening and structure
      determination.
AB  - This paper describes the NMR screening of 141 small (<15 kDa) recombinant
      Thermotoga maritima proteins for globular folding. The experimental data shows
      that approximately 25% of the screened proteins are folded under our screening
      conditions, which makes this procedure an important step for selecting those
      proteins that are suitable for structure determination. A comparison of screening
      based either on 1D 1H NMR with unlabeled proteins or on 2D [1H,15N]-COSY with
      uniformly 15N-labeled proteins is presented, and a comprehensive analysis of the
      1D 1H NMR screening data is described. As an illustration of the utility of these
      methods to structural proteomics, the NMR structure determination of TM1492
      (ribosomal protein L29) is presented. This 66-residue protein consists of a N
      terminal 3(10)-helix and two long alpha-helices connected by a tight turn
      centered about glycine 35, where conserved leucine and isoleucine residues in the
      two alpha-helices form a small hydrophobic core.

PMID- 15263838
TI  - Protein crystallization in the structural genomics era.
AB  - There are five broad areas where noteworthy advances have occurred in the field
      of macromolecular crystallization in the past 10 years, though some areas have
      seen the major part of those advances in only the last two years. This is largely
      a consequence of the international structural genomics initiative and its early
      results. The five areas are: (1) Physical studies and characterization of the
      protein crystallization process; (2) Development of new practical approaches and
      procedures; (3) The implementation of protein engineering by genetic means to
      enhance both purification and crystallization; (4) The creation of new screening
      conditions based on information and databases emerging from structural genomics;
      and (5) Development and implementation of automation, robotics, and mass
      screening of crystallization conditions using very small amounts of protein. A
      brief summary is provided here of the progress in the past few years and the
      influence of the structural genomics project.

PMID- 15263839
TI  - Primer Prim'er: a web based server for automated primer design.
AB  - The Northeast Structural Genomics Consortium (NESG) is one of nine NIH-funded
      pilot projects created to develop technologies needed for structural studies of
      proteins on a genome-wide scale. One of the most challenging aspects of this
      emerging field is the production of protein samples amenable to structural
      determination. To do this efficiently, all steps in the protein production
      pipeline must be automated. Here we describe the Primer program (linked from
      http://www-nmr.cabm.rutgers.edu/bioinformatics, www
      nmr.cabm.rutgers.edu/bioinformatics, a web-based primer design program freely
      available to the scientific community, which was created to automate this time
      consuming and laborious task. This program has the ability to simultaneously
      calculate plasmid specific primer sets for multiple open reading frame (ORF)
      targets, including 96-well and greater formats. Primer includes a library of
      commonly used plasmid systems and possesses the ability to upload user-defined
      plasmid systems. In addition to calculating gene-specific annealing regions for
      each target, the program also adds appropriate restriction endonuclease
      recognition or viral recombination sites while preserving a reading frame with
      plasmid based fusions. Primer has several useful features such as sorting
      calculated primer sets by target size, facilitating interpretation of PCR
      amplifications by agarose gel electrophoresis, as well as supplying the molecular
      biologist with many important characteristics of each target such as the expected
      size of the PCR amplified DNA fragment and internal restriction sites. The NESG
      has cloned over 1500 genes using oligonucleotide primers designed by Primer.

PMID- 15263840
TI  - An automated small-scale protein expression and purification screening provides
      beneficial information for protein production.
AB  - One of the first key steps in structural genomics is high-throughput expression
      and rapid screening to select highly soluble proteins, the preferred candidates
      for crystal production. Here we describe the methodology used at the Berkeley
      Structural Genomics Center (BSGC) for automated parallel expression and small
      scale purification of fusion proteins using a 96-well format. Our robotic method
      includes cell lysis, soluble fraction separation and purification with affinity
      resins. For detection of His-tagged proteins in the soluble fractions and after
      affinity resin elution, a dot-blot procedure with an anti-His-antibody is used.
      The expression level and molecular mass of recombinant proteins are checked by
      SDS-PAGE. With this approach, we are able to obtain beneficial information to be
      used for large-scale protein expression and purification.

PMID- 15263841
TI  - Establishing a versatile fermentation and purification procedure for human
      proteins expressed in the yeasts Saccharomyces cerevisiae and Pichia pastoris for
      structural genomics.
AB  - We describe the introduction of the yeasts Saccharomyces cerevisiae and Pichia
      pastoris as eukaryotic hosts for the routine production of recombinant proteins
      for a structural genomics initiative. We have previously shown that human cDNAs
      can be efficiently expressed in both hosts using high throughput procedures.
      Expression clones derived from these screening procedures were grown in
      bioreactors and the over-expressed human proteins were purified, resulting in
      obtaining significant amounts suitable for structural analysis. We have also
      developed and optimized protocols enabling a high throughput, low cost
      fermentation and purification strategy for recombinant proteins for both S.
      cerevisiae and P. pastoris on a scale of 5 to 10 mg. Both batch and fed batch
      fermentation methods were applied to S. cerevisiae. The fed batch fermentations
      yielded a higher biomass production in all the strains as well as a higher
      productivity for some of the proteins. We carried out only fed batch
      fermentations on P. pastoris strains. Biomass was produced by cultivation on
      glycerol, followed by feeding methanol as carbon source to induce protein
      expression. The recombinant proteins were expressed as fusion proteins that
      include a N-terminal His-tag and a C-terminal Strep-tag. They were then purified
      by a two-step chromatographic procedure using metal-affinity chromatography and
      StrepTactin-affinity chromatography. This was followed by gel filtration for
      further purification and for buffer exchange. This three-step purification
      procedure is necessary to obtain highly purified proteins from yeast. The
      purified proteins have successfully been subjected to crystallization and
      biophysical analysis.

PMID- 15263843
TI  - Cloning grills: high throughput cloning for structural genomics.
AB  - Cloning grills are aluminum grids designed to divide an agar plate into segments,
      thereby multiplying the number of E. coli cultures which can be streaked out on a
      single plate. The grills are autoclaved and placed in square petri dishes
      immediately after hot agar is poured. When the agar solidifies, the grill remains
      embedded in the media, and each of the 12 lanes accommodates the streaking out of
      a single culture. As the spacing of the grill lanes is the same as that of a 96
      well plate, 12 cultures can be streaked at a time using a 12-channel pipette.
      This allows a plate of 96 cultures to be rapidly and accurately plated for colony
      isolation on only eight agar plates.

PMID- 15263842
TI  - High-throughput, genome-scale protein production method based on the wheat germ
      cell-free expression system.
AB  - Current cell-free protein expression systems are capable of synthesizing proteins
      with high speed and accuracy; however, the yields are low due to their
      instability over time. Escherichia coli based systems are not always sufficient
      for expression of eukaryotic proteins. This report reviews a high-throughput
      protein production method based on the cell-free system prepared from eukaryote,
      wheat embryos. We first demonstrate a method for preparation of this extract that
      exhibited a high degree of stability and activity. To maximize translation yield
      and throughput, we address and resolve the following issues: (1) optimization of
      the ORF flanking regions; (2) PCR-based generation of DNA for mRNA production;
      (3) expression vectors for large-scale protein production; and (4) a translation
      reaction that does not require a membrane. The combination of these elemental
      processes with robotic automation resulted in high-throughput protein synthesis.

PMID- 15263844
TI  - Preparation of Escherichia coli cell extract for highly productive cell-free
      protein expression.
AB  - As structural genomics and proteomics research has become popular, the importance
      of cell-free protein synthesis systems has been realized for high-throughput
      expression. Our group has established a high-throughput pipeline for protein
      sample preparation for structural genomics and proteomics by using cell-free
      protein synthesis. Among the many procedures for cell-free protein synthesis, the
      preparation of the cell extract is a crucial step to establish a highly efficient
      and reproducible workflow. In this article, we describe a detailed protocol for
      E. coli cell extract preparation for cell-free protein synthesis, which we have
      developed and routinely use. The cell extract prepared according to this protocol
      is used for many of our cell-free synthesis applications, including high
      throughput protein expression using PCR-amplified templates and large-scale
      protein production for structure determinations.

PMID- 15263845
TI  - Using an Escherichia coli cell-free extract to screen for soluble expression of
      recombinant proteins.
AB  - For structural and functional genomics programs, new high-throughput methods to
      characterize well-expressing and highly soluble proteins are essential. A faster
      and more convenient approach to screen expression conditions of recombinant
      proteins compared to classical in vivo systems is the Escherichia coli cell-free
      expression system. Here, we describe a rapid procedure to screen for expression
      and solubility of recombinant proteins using an E. coli cell-free extract. The
      results presented cover 24 open reading frames of unknown function from different
      micro-organisms. In order to screen different variables that may interfere with
      solubility, we expressed the recombinant proteins with a histidine6 tag, either N
      terminal or C-terminal at two temperatures (25 degrees C and 30 degrees C). The
      identification of recombinant proteins is performed by the dot blot procedure
      using an anti-histidine tag antibody. We designed a rapid method that allows the
      characterization of soluble candidates from a large number of genes or from a
      large number of variants that is highly compatible with structural genomics
      expectations.

PMID- 15263846
TI  - SUMO fusions and SUMO-specific protease for efficient expression and purification
      of proteins.
AB  - SUMO (small ubiquitin-related modifier) modulates protein structure and function
      by covalently binding to the lysine side chains of the target proteins. Yeast
      cells contain two SUMO proteases, Ulp1 and Ulp2, that cleave sumoylated proteins
      in the cell. Ulp1 (SUMO protease 1) processes the SUMO precursor to its mature
      form and also de-conjugates SUMO from side chain lysines of target proteins. Here
      we demonstrate that attachment of SUMO to the N-terminus of under-expressed
      proteins dramatically enhances their expression in E. coli. SUMO protease 1 was
      able to cleave a variety of SUMO fusions robustly and with impeccable
      specificity. Purified recombinant SUMO-GFPs were efficiently cleaved when any
      amino acid, except proline, was in the+1 position of the cleavage site. The
      enzyme was active over a broad range of buffer and temperature conditions.
      Purification of certain recombinant proteins is accomplished by production of Ub
      fusions from which Ub can be subsequently removed by de-ubiquitinating enzymes
      (DUBs). However, DUBs are unstable enzymes that are difficult to produce and
      inexpensive DUBs are not available commercially. Our findings demonstrate that
      SUMO protease 1/SUMO-fusion system may be preferable to DUB/Ub-fusion. Enhanced
      expression and solubility of proteins fused to SUMO combined with broad
      specificity and highly efficient cleavage properties of the SUMO protease 1
      indicates that SUMO-fusion technology will become a useful tool in purification
      of proteins and peptides.

PMID- 15263847
TI  - Production in two-liter beverage bottles of proteins for NMR structure
      determination labeled with either 15N- or 13C-15N.
AB  - The use of 2-L polyethylene terephthalate beverage bottles as a bacterial culture
      vessel has been recently introduced as an enabling technology for high-throughput
      structural biology [Sanville Millard, C. et al., 2003. Protein Express. Purif.
      29, 311-320]. In the article following this one [Stols et al., this issue, pp. 95
      102], this approach was elaborated for selenomethionine labeling used for
      multiwavelength anomalous dispersion phasing in the X-ray crystallographic
      determinations of protein structure. Herein, we report an effective and
      reproducible schedule for uniform 15N- and 13C-labeling of recombinant proteins
      in 2-L beverage bottles for structural determination by NMR spectroscopy. As an
      example, three target proteins selected from Arabidopsis thaliana were expressed
      in Escherichia coli Rosetta (DE3)/pLysS from a T7-based expression vector,
      purified, and characterized by electrospray ionization mass spectrometry and NMR
      analysis by 1H-15N heteronuclear single quantum correlation spectroscopy. The
      results show that expressions in the unlabeled medium provide a suitable control
      for estimation of the level of production of the labeled protein. Mass spectral
      characterizations show that the purified proteins contained a level of isotopic
      incorporation equivalent to the isotopically labeled materials initially present
      in the growth medium, while NMR analysis of the [U-15N]-labeled proteins provided
      a convenient method to assess the solution state properties of the target protein
      prior to production of a more costly double-labeled sample.

PMID- 15263848
TI  - Production of selenomethionine-labeled proteins in two-liter plastic bottles for
      structure determination.
AB  - A simplified approach developed recently for the production of heterologous
      proteins in Escherichia coli uses 2-liter polyethylene terephthalate beverage
      bottles as disposable culture vessels [Sanville Millard, C. et al. 2003. Protein
      Expr. Purif. 29, 311-320]. The method greatly reduces the time and effort needed
      to produce native proteins for structural or functional studies. We now
      demonstrate that the approach is also well suited for production of proteins in
      defined media with incorporation of selenomethionine to facilitate structure
      determination by multiwavelength anomalous diffraction. Induction of a random set
      of Bacillus stearothermophilus target genes under the new protocols generated
      soluble selenomethionyl proteins in good yield. Several selenomethionyl proteins
      were purified in good yields and three were subjected to amino acid analysis.
      Incorporation of selenomethionine was determined to be greater than 95% in one
      protein and greater than 98% in the other two. In the preceding paper [Zhao et
      al., this issue, pp. 87-93], the approach is further extended to production of [U
      15N]- or [U-13C, U-15N]-labeled proteins. The approach thus appears suitable for
      high-throughput production of proteins for structure determination by X-ray
      crystallography or nuclear magnetic resonance spectroscopy.

PMID- 15263849
TI  - Genome-scale expression of proteins from Bacillus subtilis.
AB  - We have applied high throughput methods for cloning and expression of more than
      850 genes from the Bacillus subtilis genome. The process uses 96-well plates and
      is automated from the level of primer design to the detection of soluble protein
      by a tag detection screen. This process was applied to a set of cytoplasmic
      targets from Bacillus subtilis to produce clones expressing soluble protein for
      incorporation into the structure determination pipeline of the Midwest Center for
      Structural Genomics. We also evaluated the feasibility of these plate-based
      methods for domain-based cloning and expression of secretory proteins and
      putative soluble domains of membrane proteins. This approach shows promise for
      implementation in a high throughput format and could provide additional target
      resources for structure determination. The continued development of new
      technologies that can be implemented in an automated format will be essential for
      continued success in the structural genomic programs.

PMID- 15263850
TI  - Automation of protein purification for structural genomics.
AB  - A critical issue in structural genomics, and in structural biology in general, is
      the availability of high-quality samples. The additional challenge in structural
      genomics is the need to produce high numbers of proteins with low sequence
      similarities and poorly characterized or unknown properties. 'Structural-biology
      grade' proteins must be generated in a quantity and quality suitable for
      structure determination experiments using X-ray crystallography or nuclear
      magnetic resonance (NMR). The choice of protein purification and handling
      procedures plays a critical role in obtaining high-quality protein samples. The
      purification procedure must yield a homogeneous protein and must be highly
      reproducible in order to supply milligram quantities of protein and/or its
      derivative containing marker atom(s). At the Midwest Center for Structural
      Genomics we have developed protocols for high-throughput protein purification.
      These protocols have been implemented on AKTA EXPLORER 3D and AKTA FPLC 3D
      workstations capable of performing multidimensional chromatography. The automated
      chromatography has been successfully applied to many soluble proteins of
      microbial origin. Various MCSG purification strategies, their implementation, and
      their success rates are discussed in this paper.

PMID- 15263851
TI  - Expression screening, protein purification and NMR analysis of human protein
      domains for structural genomics.
AB  - Structural genomics, the determination of protein structures on a genome-wide
      scale, is still in its infancy for eukaryotes due to the number and size of their
      genes. Low protein expression and solubility of eukaryotic geneproducts are the
      major bottlenecks in high-throughput (HTP) recombinant protein production with
      the E. coli expression systems. To circumvent this problem we decided to focus on
      separate protein domains. We describe here a fast microtiterplate based,
      expression and solubility screening procedure, using a combination of in vitro
      and in vivo expression, and purification with nickel-NTA magnetic beads. All
      steps are optimized for automatic HTP processing using a liquid handling station.
      Furthermore, large-scale expression and protein purification conditions are
      optimized, permitting the purification of 24 protein samples per week. We further
      show that results obtained from the expression screening can be extrapolated to
      the production of protein samples for NMR. Starting with 81 cloned human protein
      domains, in vivo expression was detected in 54 cases, and from 28 of those
      milligrams of protein were purified. An informative HSQC spectrum was recorded
      for 18 proteins (22%), half of which were indicative of a folded protein. The
      success rate and quality of the HSQC spectra suggest that the domain approach
      holds promise for human proteins.

PMID- 15263852
TI  - A scaleable and integrated crystallization pipeline applied to mining the
      Thermotoga maritima proteome.
AB  - The wealth of genomic data available for many organisms has set the stage for the
      next phase of structure-function analysis. High-throughput structural genomics is
      currently the method of choice for rapid analysis of protein structure-function
      relationships on a proteome-wide basis. The Joint Center for Structural Genomics
      (JCSG), established in 2000 under the NIH/NIGMS Protein Structure Initiative, has
      developed and implemented an integrated high-throughput structure pipeline and
      applied it in a 2-tiered approach to mining the proteome of the thermophilic
      bacterium Thermotoga maritima. In the first tier, the successful application of
      this integrated pipeline has resulted in the cloning and expression of 73% of the
      T. maritima proteome (1376 out of 1877 predicted genes), and has identified 465
      proteins which produced crystal hits. These 465 proteins were compared with
      existing structural information and a subset of 269 targets were selected to
      process towards structure determination in a second tier effort. To date, the
      JCSG pipeline applied to the Thermotoga maritima proteome has resulted in 55 new
      structures and has identified 6 novel folds and continues to identify structures
      with novel features.

PMID- 15263854
TI  - Expression of human proteins at the Southeast Collaboratory for Structural
      Genomics.
AB  - The human protein production group at the Southeast Collaboratory for Structural
      Genomics is charged with producing human proteins for both X-ray crystallography
      and NMR structural studies. Eukaryotic, and human proteins in particular, are
      notoriously difficult to express in bacterial systems. For various reasons, T7
      based expression often results in protein expressed in an insoluble form.
      Overcoming this requires either introduction of a step to screen expression
      conditions or inclusion of a troublesome refolding step during purification. Our
      laboratory uses a trc-based expression vector that addresses many of the
      difficulties of the commonly used T7-based expression systems. Proteins expressed
      under the trc promoter, a weak promoter compared to the strong T7 promoter, are
      produced in a soluble form and include necessary cofactors. The details of this
      system will be discussed.

PMID- 15263853
TI  - Laboratory scale structural genomics.
AB  - At Lawrence Livermore National Laboratory, the development of the TB structural
      genomics consortium crystallization facility has paralleled several local
      proteomics research efforts that have grown out of gene expression microarray and
      comparative genomics studies. Collective experience gathered from TB consortium
      labs and other centers involved in the NIH-NIGMS protein structure initiative
      allows us to explore the possibilities and challenges of pursuing structural
      genomics on an academic laboratory scale. We discuss our procedures and protocols
      for genomic targeting approaches, primer design, cloning, small scale expression
      screening, scale-up and purification, through to automated crystallization
      screening and data collection. The procedures are carried out by a small group
      using a combination of traditional approaches, innovative molecular biochemistry
      approaches, software automation, and a modest investment in robotic equipment.

PMID- 15263855
TI  - Towards higher-throughput membrane protein production for structural genomics
      initiatives.
AB  - Integral membrane proteins present unparalleled challenges for structural
      genomics programs. Samples from this class of proteins are not only difficult to
      produce in quantities sufficient for analysis by X-ray diffraction or NMR, but
      their hydrophobic properties add extra dimension to their purification and
      subsequent crystallization. New systems that seek to tackle the production
      problems are in development. In our laboratory, one such strategy exploits the
      unique physiology of the Rhodobacter species of photosynthetic bacteria where we
      have designed an overexpression system that coordinates the heterologous
      production of targeted hydrophobic proteins with nascent, unfilled membranes that
      can be used to harbor them. In this study, we describe the means by which
      purification of recombinant membrane proteins produced in such a fashion can be
      purified efficiently from Rhodobacter membranes using relatively higher
      throughput, semi-automated methods. These protocols utilize a state-of-the-art
      FPLC system for affinity chromatography, followed by gel filtration or ion
      exchange chromatography to enhance purity for crystallization attempts. The
      Rhodobacter expression system coupled with the semi-automation of purification
      steps represents an advance towards the development of a strategy for obtaining
      structures for membrane proteins at a more rapid pace.

PMID- 15263856
TI  - Evaluation of seizure-like episodes in survivors of moderate and severe traumatic
      brain injury.
AB  - BACKGROUND: Transient paroxysmal alterations of consciousness or behavior are
      common sequelae of moderate and severe traumatic brain injury (TBI). Clinicians
      caring for patients with such episodes often diagnose them as epileptic seizures,
      a frequent and well-studied complication of TBI. As it is difficult to confirm
      this diagnosis, antiepileptic drugs are often used empirically. However, as such
      therapy is frequently ineffective, we studied the usefulness of prolonged video
      electroencephalogram (VEEG) monitoring in the clinical management of paroxysmal
      behaviors in TBI survivors. METHODS: Records of patients referred evaluation in
      an epilepsy monitoring unit for management of medically intractable epilepsy were
      retrospectively reviewed. Patients with a documented history of moderate-to
      severe brain injury preceding the onset of epilepsy were identified. These
      patients were studied by simultaneous videotape and scalp electroencephalographic
      recordings, and the majority also underwent magnetic resonance imaging and
      neuropsychologic studies. RESULTS: Of the 1858 consecutive admissions over a 66
      month period, 127 (7%) fulfilled enrollment criteria. VEEG monitoring was
      conducted for an average of 4.6 days. Monitoring was successful in establishing a
      diagnosis in 82% of the cases referred: 62% had focal seizures, 6% had
      generalized seizures, and 33% had psychogenic nonepileptic seizures. Of those
      with temporal lobe epilepsy, 53% had mesial temporal sclerosis, as shown by
      magnetic resonance imaging. CONCLUSIONS: VEEG is a useful procedure in the
      evaluation of TBI survivors with spells. The yield of diagnoses that may alter
      treatment is substantial. Additionally, mesial temporal sclerosis is associated
      with TBI. Given the variety of seizure types found in survivors of moderate-to
      severe TBI, obtaining specific diagnosis of seizure type by VEEG monitoring
      impacts treatment options.

PMID- 15263858
TI  - Movement disorders after head injury: diagnosis and management.
AB  - Head injury can cause extrapyramidal movement disorders such as tremors,
      parkinsonism, dystonia, chorea, myoclonus, and tics. Pure adventitious movements
      are rare, but combinations with paresis, spasticity, apraxia, or ataxia occur in
      approximately 20% of cases of severe head injury, in many cases appearing or
      evolving in the months following the injury. Tremors may improve in time but many
      of the other syndromes tend to persist. Reversible causes such as medications or
      metabolic derangements are occasionally identifiable. Some of these adventitious
      movements can be improved using neuroactive drugs, botulinum toxin injections, or
      stereotactic brain surgery.

PMID- 15263857
TI  - Medical and social issues related to posttraumatic seizures in persons with
      traumatic brain injury.
AB  - BACKGROUND: The incidence of late posttraumatic seizures (LPTS) in individuals
      with traumatic brain injury (TBI) ranges anywhere from 5% to 18.9% in civilian
      populations up to 32% to 50% in military personnel. OBJECTIVE: This article
      reviews the current knowledge about the incidence and prevalence of LPTS
      following a TBI, the risk factors for developing LPTS, and the options available
      for preventing the development of LPTS. METHODS: The psychosocial ramifications
      of LPTS following a TBI have not been well explored. As a result, the
      psychosocial findings from the current literature on epilepsy will be reviewed
      with the hope that the need for future TBI outcomes research to investigate the
      impact of LPTS following a TBI or, at least, to include LPTS as a potential
      contributing factor will be recognized.

PMID- 15263859
TI  - Change and predictors of change in communication, cognition, and social function
      between 1 and 5 years after traumatic brain injury.
AB  - OBJECTIVE: To study cognitive, communication, and social changes experienced by
      individuals between 1 and 5 years after traumatic brain injury (TBI). DESIGN:
      Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database with 927
      eligible subjects using a cohort with complete 1- and 5-year data (N = 292). MAIN
      OUTCOME MEASURES: Change in Functional Independence Measure trade mark -Cognitive
      (FIM-Cog) items from Year 1 to Year 5 postinjury. RESULTS: On the FIM-Cog Total
      score, 26% individuals improved, 61% stayed the same, and 14% worsened by more
      than 1 point from Year 1 to Year 5. On the 2 FIM Communication items, 19%
      individuals improved, 68% stayed the same, and 13% worsened by greater than 1
      point. On the FIM Social Interaction item, 12% individuals improved, 76% stayed
      the same, and 11% worsened. On the FIM Memory and Problem Solving items, 34%
      individuals improved, 48% stayed the same, and 19% worsened. Several variables
      predicted this improvement and worsening, some of which were available at the
      time of injury and most were those available at 1 year postinjury. The Memory and
      Problem Solving items, taken together, showed fewer participants at ceiling at
      Year 1 and more change between Year 1 and Year 5 compared to the Communication
      and Social Interaction items. CONCLUSIONS: Many individuals did not demonstrate
      meaningful change on FIM-Cog and its component items from Year 1 to Year 5. In
      particular, a high proportion of improvement was observed in Memory/Problem
      Solving, and worsening in Social Interaction. Demographic and functional
      indicators present at 1 year postinjury may be predictive of subsequent change.

PMID- 15263860
TI  - Fighting the silent epidemic: the Florida Brain and Spinal Cord Injury Program.
AB  - This article describes a statewide model program that provides a range of
      services for individuals with traumatic brain injury in Florida. The article
      answers questions regarding the organization, delivery, and financing of a system
      that includes surveillance data, case management, health services, a network of
      contractors, and a Medicaid waiver. With an annual budget of more than 15 million
      US dollars, the primary source of financing is a trust fund established through
      state statute with revenues from fines levied for driving while intoxicated.
      Lessons from Florida that will be useful to states as they respond to Olmstead
      and develop Medicaid waivers include (a) how a data registry laid the foundation
      for a service delivery system, (b) how early and aggressive case management has
      the potential for Medicaid savings, and (c) how a statewide system, critical mass
      of patients, and standards for providers can improve the quality of services for
      persons with traumatic brain injury.

PMID- 15263861
TI  - Ecological validity of walking speed assessment after traumatic brain injury: a
      pilot study.
AB  - OBJECTIVE: To assess the ecological validity of walking speed measurement after
      traumatic brain injury (TBI). PARTICIPANTS: Ten people with TBI who could walk
      independently and were participating in a rehabilitation program. DESIGN: Walking
      speed on 3 clinical gait tests (comfortable and fast pace over a 10-m distance
      and a 6-minute walk test) in 3 "natural" environments (a corridor in a brain
      injury rehabilitation unit, a car park of a metropolitan shopping center, and
      inside a metropolitan shopping center). Normative data were collected for 275
      able-bodied pedestrians as they walked in the 3 natural environments. RESULTS:
      For subjects with TBI, agreement between the speeds used in the clinical gait
      tests and the natural environments was poor (intraclass correlation coefficient
      [ICC] values ranged from -0.24 to 0.63). The closest speed match was the
      comfortable paced 10-m walk test and walking in a corridor of a brain injury
      rehabilitation unit (ICC 0.63). Able-bodied pedestrians walked at significantly
      faster speeds than did subjects with TBI in all 3 natural environments.
      CONCLUSIONS: Comfortable walking speed appears to have the highest ecological
      validity of the clinical gait tests investigated. Practice in natural and more
      complex environments should be incorporated into walking rehabilitation programs
      for people with TBI.

PMID- 15263863
TI  - Creating an aggregate outcome index: cost-effectiveness analysis of substance
      abuse treatment.
AB  - This article proposes a method of calculating a practical index of improvement
      for conducting a cost-effectiveness analysis of substance abuse treatment. While
      the methodology of cost-effectiveness analysis necessitates the use of a single
      outcome measure, substance abuse treatment can produce multiple, important
      outcomes that must be considered in policy decisions about funding and
      alternative treatments. Thus, there is a need to aggregate the variety of
      outcomes from substance abuse treatment into a single index. The proposed index
      is a preference-weighted sum of outcomes using data from the Addiction Severity
      Index. The methodology and use of the index for conducting a cost-effectiveness
      analysis are illustrated using Addiction Severity Index data from a controlled
      quasi-experimental field study of case management.

PMID- 15263864
TI  - Racial differences in the mental health needs and service utilization of youth in
      the juvenile justice system.
AB  - Mental health placement rates by the juvenile justice system differ by race.
      However, it is unknown whether mental health needs differ by race. This study
      attempted to investigate potential differences in mental health needs and service
      utilization among Caucasian, African American, and Hispanic juvenile justice
      involved youth. A stratified random sample of 473 youth petitioned, adjudicated,
      and incarcerated from 1995-1996 was examined using a standard chart review
      protocol and the Childhood Severity of Psychiatric Illness measure for mental
      health needs. Significant and unique mental health needs were demonstrated for
      all racial groups. African American youth demonstrated the greatest level of
      needs. Minority status indicated significantly lower rates of mental health
      service utilization. Minority youth in the juvenile justice system are most at
      risk for underserved mental health needs. Based on the current data, it can be
      inferred that the first contact with the state's child and adolescent serving
      system, which includes the juvenile justice and mental health sectors, appears to
      be through the juvenile justice sector for many minority youth with delinquency
      problems.

PMID- 15263865
TI  - Provider turnover in public sector managed mental health care.
AB  - The present study examines the extent of turnover in mental health provider
      networks within public sector managed mental health care over a 1-year period and
      its association to provider and practice characteristics. Telephone interviews
      were conducted with a sample of mental health services providers listed the
      previous year in the networks of the 3 public sector managed mental health care
      organizations operating in Puerto Rico. Thirty-one percent of respondents had
      dropped out of networks. The drop-out rate was significantly associated (P < or =
      .05) with increasing number of years in practice and decreasing years under
      contract. A nonsignificant trend was observed, suggesting that providers with
      subspecialty training are less likely to drop out. The results may be signaling
      an emerging problem in public sector managed mental health care. Stability of
      provider networks should be monitored by state agencies contracting out mental
      health care.

PMID- 15263866
TI  - A test of mental health parity: comparisons of outcomes of hospital concurrent
      utilization review.
AB  - The Mental Health Parity Act of 1996 had as its goal the equity of coverage of
      mental health care and physical health care. The purpose of this study was to
      examine the outcomes of hospital concurrent utilization review as a measure of
      the progress toward the equity goal. The study examined 4 years of denials of
      certification for reimbursement by payers of inpatient care (1998-2001).
      Psychiatry was first compared to clinical services with a like number of annual
      admissions and then compared to clinical services with a like number of
      concurrent reviews. For each year, psychiatry had the highest numbers of cases
      denied and patient days denied. The most frequent reason for a psychiatric denial
      was that the inpatient benefit level had been exceeded. There was only one
      instance, in 4 years, when this reason (benefit limit exceeded) was given for a
      patient with a physical illness. This study provides evidence of the current
      inequity of reimbursement for treatment of mental illness.

PMID- 15263867
TI  - Continuity of care: validation of a new self-report measure for individuals using
      mental health services.
AB  - Continuity of care is a concern for individuals with persistent mental illness
      who need diverse services over time in response to multiple and changing needs.
      Efforts to study continuity have been hampered by lack of appropriate
      instruments. The Alberta Continuity of Services Scale--Mental Health is a newly
      developed, self-report scale that assesses continuity of care across settings and
      providers. This study examined the structure, reliability, and validity of the
      measure among users of community mental health programs. Findings were positive.
      Scores captured both positive and negative perceptions of care. Factor analyses
      elucidated 3 components of continuity--system access, interpersonal aspects, and
      care team function. Associations between the continuity scores and selected
      client and service use measures supported its validity. The tool holds promise
      for system monitoring, but would need refinements to create a shorter,
      conceptually clearer version. Also, performance among individuals with mild and
      very severe levels of mental illness needs to be evaluated.

PMID- 15263868
TI  - Gender differences in patterns of risk factors among children receiving mental
      health services: latent class analyses.
AB  - Latent class analyses were used to analyze data from a sample of children
      participating in the national evaluation of the Comprehensive Communities Mental
      Health Services for Children and Their Families Program (N = 6786). Lifetime risk
      experiences of the child were analyzed to identify 4 classes of boys and girls
      with similar risk patterns. While low-risk, status-offense, abuse, and high-risk
      classes were identified for both boys and girls, there were nearly half the
      number of girls in the low-risk class, almost as many in the status-offense
      class, twice as many in the abuse class, and more than 3 three times as many in
      the high-risk class as there were boys. These findings suggest that there are
      specific groups of children entering services who differ as a function of their
      lifetime risk exposure. In addition, the relationship between class membership
      and child functioning, and class membership and family lifetime risk experiences.
      Understanding these differences provides critical information to the service
      planning process. In addition, it may result in immediate improvement in the
      triage of children into services and a better understanding of their behaviors
      during and after treatment.

PMID- 15263869
TI  - Healthcare use by children with attention deficit/hyperactivity disorder with and
      without psychiatric comorbidities.
AB  - This study examined healthcare services used by children with attention
      deficit/hyperactivity disorder (ADHD), with and without psychiatric
      comorbidities. The study was conducted in a large health maintenance organization
      in the Pacific Northwest on all continuously enrolled children aged 5 to 12 from
      January 1997 through July 1998. The study measured all outpatient medical care,
      specialty mental health care services, and prescription drug dispensings from
      computer records. Children with ADHD, with and without other psychiatric
      comorbidities, use more general medical services than do other groups of
      children, including outpatient visits, acute care (emergency room [ER] urgent
      care) visits. ADHD and other psychiatric comorbidities lead to higher use of
      specialty mental health services and greater use of psychotropic medications.

PMID- 15263870
TI  - A Need-based model for determining staffing needs for the public sector
      outpatient mental health service system.
AB  - This article proposes a need-based model for determining staffing needs for
      regional or national public sector outpatient mental health services. It
      constitutes a spreadsheet method involving a sequence of calculations relating
      demographic variables, workers' productivity, anticipated demand, and standards
      pertaining to annual visits per client distributed among the core mental health
      professions. The authors demonstrate the application of the model to national
      planning of adult outpatient mental health services using standards based on both
      expert consensus and existing staffing patterns while they note the need for more
      rigorously derived and empirically based standards. It is suggested that by using
      clearly stated assumptions and quantifiable variables, the model can facilitate
      constructive negotiations among various agencies and community organizations
      involved in policymaking and in budget allocations.

PMID- 15263871
TI  - The TEFRA medicaid eligibility option for children with severe disabilities: a
      national study.
AB  - The Tax Equity and Fiscal Responsibility Act (TEFRA) Medicaid Eligibility Option,
      also known as the Katie Beckett Option, was developed to allow children with
      disabilities from near-poor and middle-income families to qualify for Medicaid.
      TEFRA has been available since 1982; however, little is known about the number of
      children served and their qualifying disability. This first national study found
      that 20 states enrolled nearly 25,000 children in 2001. Only 10 of these states
      allowed children to qualify because of a mental health disability. Additional
      research is needed to understand the role of TEFRA in providing insurance to
      children with disabilities.

PMID- 15263874
TI  - Performance-enhancing drugs.

PMID- 15263875
TI  - Catheter ablation of atrial fibrillation.

PMID- 15263876
TI  - Autogenous and xenogeneic bone grafts for the bone regeneration. A literature
      review.
AB  - The aim of this article is to investigate 2 groups of biomaterials widely used in
      the surgical procedures for bone regeneration in dentistry: autograft and
      xenograft bone. An insufficient bone volume is the main condition for the long
      life stability of osteointegrated implants. Thanks to the numerous surgical
      procedures and fervent research, the possibility to rebuild the bone is now much
      more predictable than in the past. This has provided the clinician with more
      solutions to handle complex situations. In the last decade, the demand for
      regenerative surgery for functional and aesthetic reasons has increased. The
      autogenous bone graft is considered the gold standard material for any
      regeneration procedures, because of its main properties: it is osteogenetic,
      osteoinductive and osteoconductive. The autogenous bone can be harvested from 2
      different sites: the intraoral and the extraoral sites. Intraoral donor site are
      the symphysis of the mandible, the mandibular ramus and the maxillary tuberosity.
      Extraoral donor site are the iliac crest, the tibia and the skull. The xenogeneic
      bone graft is a graft that has been taken from a donor of another species. These
      natural materials, thanks to their chemical-physical characteristics similar to
      those of the human bone, show great osteoconductive properties.

PMID- 15263877
TI  - Technological characteristics and clinical indications of piezoelectric bone
      surgery.
AB  - Piezoelectric bone surgery, also simply known as piezosurgery, is a new technique
      for osteotomy and osteoplasty utilizing an innovative ultrasonic surgical
      apparatus. This technique was created and developed in response to the need to
      reach major levels of precision and safety in bone surgery, as compared to that
      available by the usual manual and motorized instruments. The instrument which
      offers these results, known as the Mectron Piezosurgery Device, is characterized
      by piezoelectric ultrasonic vibrations of a frequency of 29 kHz and a range
      between 60/200 Hz. Due to their characteristics, the microvibrations allow a
      selective cut of only mineralized structures without damaging soft tissues, which
      remain undamaged even in case of accidental contact. The micrometric vibration
      ensures precise cutting action and at the same time maintains a blood-free site
      because of the physical phenomenon of cavitation. The micrometric vibration makes
      the instrument manageable and permits major interoperative control with a
      consequent increase in safety especially in anatomically difficult areas. The
      absence of macrovibrations makes the instrument more manageable and allows
      greater interoperative control with a significant increase in the cutting safety
      in the more difficult anatomical cutting zones. Given its innovative nature,
      piezosurgery distinguishes itself as being different from the conventional
      techniques utilised in bone surgery. Consequently, it requires different surgical
      skill. To master the right surgical skill it is essential to demonstrate an
      adequate learning curve.

PMID- 15263878
TI  - Peri-implant diseases. A systematic review of the literature.
AB  - Peri-implantitis surrounding oral implants is an inflammatory process affecting
      the soft and hard tissues resulting in rapid loss of supporting bone associated
      with bleeding and suppuration. The etiopathogenesis of early and late peri
      implantitis is less well understood and seems to be related to the peri-implant
      environment and to the soft tissues/implant interface, to patient-related factors
      (smoke, systemic diseases, plaque control) and to host-parasite equilibrium.
      However, there is wide scientific evidence that demonstrates the direct
      correlation between oral microbiota and peri-implant mucositis or peri
      implantitis. In particular, adherence and colonization of microbiota on plaque
      exposed biomaterials, like c.p. titanium, are discriminant factors for the
      development of infection. Regenerative or resective surgical approaches are
      proposed for the treatment of peri-implantitis depending on the morphology and
      the shape of bone defects. The therapeutical approach of peri-implantitis
      surrounding dental implants comprises several aspects such as the removal of
      supra-gingival bacterial plaque, an appropriate surgical approach, the removal of
      granulation tissue and detoxification of the exposed implant surface, the
      elimination of the anaerobic ecosystem by the removal of peri-implant pocket
      (gingivectomy or apically repositioned flap) or by the regeneration of the peri
      implant hard tissues and, finally, the establishment of an efficient plaque
      control regimen.

PMID- 15263879
TI  - Occlusal features are not a reliable predictor of bruxism.
AB  - AIM: The aim of this investigation was to estimate the contribution of occlusion
      to differentiate bruxers from non-bruxers. METHODS: Participants in the study
      were 160 patients consecutively selected among 20-30 year old patients attending
      the Section of Prosthetic Dentistry for conservative care. The presence of
      bruxism was clinically and anamnestically investigated. In each patient the
      following occlusal features were recorded: retruded contact position-intercuspal
      position slide length, vertical overlap, horizontal overlap, unilateral posterior
      crossbite, incisor dental midline discrepancy, mediotrusive interferences,
      laterotrusive interferences. A stepwise logistic regression model was used to
      identify the significant associations between occlusal features and bruxism.
      RESULTS: Diagnosis of bruxism was made in 67/160 subjects (41.8%). Differences
      between sex were not significant (p=0.814). Among the 8 occlusal variables
      included in the logistic regression analysis, those remaining in the final model
      were laterotrusive interferences (OR 2.47) and anterior open-bite (OR 0.88). This
      model showed good specificity (87%) but an unacceptable sensitivity (26.9%) to
      predict bruxism (accuracy=61.6%). Therefore, multivariate analysis did not lead
      to an improvement in bruxism predictability with respect to univariate analysis,
      which revealed that the presence of bruxism was significantly associated with
      laterotrusive interferences alone (p=0.040), and not with unilateral cross-bite
      (p=0.208), anterior open-bite (p=0.202), deep-bite (p=0.572), large horizontal
      overlap (p=0.261), dental midline discrepancy (p=0.519), mediotrusive
      interferences (p=0.119), slide >or=2 mm (p=0.857). CONCLUSION: According to our
      findings the contribution of occlusion to differentiate bruxers from non-bruxers
      is very poor. Infact, only laterotrusive interferences seem to be significantly
      associated with bruxism.

PMID- 15263880
TI  - Combined sedation with oral chlordemethyldiazepam and midazolam by nasal route in
      third molar surgery.
AB  - AIM: This study was performed to evaluate the effects on the cardiocirculatory
      system, on perioperative anxiety and compliance of sedation with 2
      benzodiazepines, chlordemethyldiazepam (CDDZ) a long acting oral drug for
      presedation and midazolam, a short acting drug, administered by nasal route to
      induce intraoperative sedation. METHODS: Fifty randomized patients undergoing
      third molar extraction at the Dental Clinic, University of Padua, were
      preoperatively evaluated. Anxiety was evaluated through a visual, analogue, scale
      (VAS) of 10 cm, a questionnaire of adjectives called interval scale of anxiety
      response (ISAR) and the Newman test was applied to evaluate the changes in
      psychomotor functions. All patients were treated with 1 ml of oral CDDZ for
      presedation and midazolam by the nasal route for intraoperative sedation at doses
      of 1 mg in Group 1 (25 patients) and 2 mg in Group 2 (25 patients). In all
      patients preoperative cardiocirculatory parameters were evaluated and in the
      first 20 min after the beginning of intervention. At the end of intervention the
      Newman test was reapplied, anxiety and postoperative cardiocirculatory data were
      reevaluated and the quality of the intervention judged in an interview made 1
      week after the intervention (quality of the sedation technique, perioperative
      pain intensity, assumption of analgesic drugs, swelling, amnesia etc. after
      intervention). RESULTS: The treatment with 1 mg CDDZ + 2 mg midazolam by nasal
      route is the best association to slightly attenuate intra- and postoperative
      cardiocirculatory response, anxiety and to improve the quality of the treatment
      without interfering on the psychomotor response of patients at the time of the
      discharge. CONCLUSION: To conclude, the sedative technique employed is easily
      applied by the dentist, and is safe, efficacious and well tolerated by patients.

PMID- 15263881
TI  - A clinical radiographic and histologic revaluation of a 10 years sample of
      surgically treated cysts of the jaws, with special emphasis on keratocysts.
AB  - AIM: The aim of this study was to compare the histologic features of the cysts as
      regards their radiographic and clinical aspects, in order to assess the accuracy
      of the diagnosis, the appropriateness of the treatment and the reliability of the
      follow-up. METHODS: A sample of 173 cysts of the jaws was reviewed in accordance
      with the 1992 WHO histological classification. RESULTS: Of these cysts, 77.44%
      were inflammatory, 12.71% follicular and 8.67% keratocysts. The cysts were
      slightly more frequently located in the mandible (52.60%) than in the maxilla
      (47.39%) and they affected men more frequently (60.11%) than women (39.88%).
      However keratocysts and nasopalatine cysts were twice as frequent in women than
      in men. No recurrence of keratocysts was found, either in those correctly
      diagnosed at the moment of the first histologic examination, or in those firstly
      erroneously diagnosed as an other type of cysts. CONCLUSION: On the basis of the
      fairly high percentage of non-inflammatory cysts in adult patients, it can be
      suggested to perform an orthopantomography as a preventive measure, every 5
      years, particularly when impaired teeth are present.

PMID- 15263882
TI  - An objective method of assessing facial swelling in patients with dental
      abscesses treated with clarithromycin.
AB  - AIM: The study evaluates the efficacy of a set of objective parameters for
      monitoring facial swelling in a group of patients treated with clarithromycin.
      METHODS: Fifty consecutive patients suffering from dental abscesses (22 in the
      maxillary arch and 28 in the mandibular arch) were enrolled. All these patients
      underwent antibiotic treatment with clarithromycin in a new formulation as a
      single daily dose (500 mg/day for 6 days). Pain and changes in facial swelling
      were evaluated at baseline and each day for 6 days through subjective parameters
      (visual analogic scale, VAS) and objective parameters (6 different tape
      measurements on the skin surface above the abscess). RESULTS: Pain and swelling
      recorded by patient and dentist (using VAS scores) showed statistically
      significant decreases (p<0.01) on days 2, 3 and 4, while no further significant
      variation was observed during days 4, 5 or 6. As regards the objective parameters
      to quantify facial swelling, the maximum dimensional change (from baseline to
      final values) in the mandibular arch was obtained with measurement 6 (mean value
      2.27+/-0.53 cm); the maximum dimensional change in the maxillary arch was
      obtained with the sum of the other 5 measurements (mean value 6.34+/-4.09 cm).
      CONCLUSION: The use of a single or a combination of linear measurements might
      provide a sensitive and reproducible method to evaluate facial swelling
      objectively and could be very useful in monitoring the efficacy of new
      antibiotics and to compare the results from different studies.

PMID- 15263884
TI  - Bone SPECT in management of mandibular condyle hyperplasia. Report of a case and
      review of literature.
AB  - In the present paper we report the case of a 14-year-old girl suffering from
      condylar hyperplasia and enlargement of ipsilateral jaw body, stressing the
      importance of bone SPECT in the clinical management of this temporomandibular
      joint (TMJ) disorder. Condylar hyperplasia is an uncommon idiopathic monolateral
      disorder of jaw growth consistent with exuberant or persistent activity of the
      condyle nucleus finally involving sociopsychological aspects due to facial
      dysmorphism. Besides facial asymmetry our patient showed prognathism,
      malocclusion, worsening otalgia and headache. Conventional X-rays examinations
      and multislice spiral CT gave us important morphostructural information also
      thanks to 3D volume-rendered and virtual reconstructions, while bone SPECT by
      detecting an intense well focused (99m)Tc-MDP uptake allowed to achieve
      uninvasively the final diagnosis of primary condyle hyperplasia. In spite of the
      full imaging characterization of TMJ disorders, consensus on best timing and
      therapeutic approaches on condylar hyperplasia is yet to be reached. In the
      present case patient was first treated orthodontically, planning a "high"
      condylectomy intervention after at least 6 months.

PMID- 15263883
TI  - [Dental offices and environment quality].
AB  - AIM: The aim of this study was to survey, from a microbiological point of view,
      dental unit water, air and surface quality in public dental offices and in
      control environments in Milan. METHODS: We studied tap and dental unit water
      (from fountain, air-water syringe, turbine), at the beginning and at the end of
      monday and thursday morning activity; air quality with surface air system (SAS)
      in dental and control offices; handpieces holder, fountain block, arm of the
      light, dental trolley, inner and outer walls surfaces quality. RESULTS: Water
      from the dental unit waterline shows average exceeding the law limits 2-3 fold
      for total bacteriological counts at 37 degrees and 22 degrees, in all examined
      points, at the beginning of the working day. There is an improvement in the water
      contamination at the end of the activity. Pseudomonas aeruginosa is frequently
      found, total and fecal coliforms are absent, while Legionella pneumophila was
      found only in one control. Air and surfaces quality is quite good, especially in
      places with ventilation systems in function. CONCLUSION: Dental unit water is the
      most critical point among those monitored. Water quality has to be improved with
      specific projects.

PMID- 15263885
TI  - Oligodontia. Surgical treatment and implant rehabilitation. A case report.
AB  - Oligodontia is the partial loss of deciduous and permanent teeth and is rather
      commonly associated with a wide range of malformations in many syndromes. The
      treatment plan for these patients is based on a multidisciplinary approach
      involving maxillo-facial surgery and several branches of dentistry. The case of a
      young man who was diagnosed with oligodontia at the age of 11 is reported. The
      patient was treated with Le Fort 1 maxillary osteotomy, sagittal palatal
      osteotomy, mandibular widening by autogenous bone grafting, endosseus titanium
      implant placement and dental rehabilitation by fixed bridges.

PMID- 15263887
TI  - Old principles in new clothes.

PMID- 15263886
TI  - Prosthetic management of neuromuscular rehabilitation in hemimandibulectomy
      patients. A case report.
AB  - The radio-surgical treatments for carcinomas involving the oral cavity are often
      destructive in order to limit as much as possible the high rate of recidivism.
      The outcome of the combined treatment is represented by lesions on hard and soft
      healthy tissues besides naturally by a more or less important mandibular
      deviation depending on greater or lesser quantity of basal bone excised. In some
      cases it is possible to surgically restore the defective mandible through bone
      grafting; this means a quite perfect restitutio ad integrum of the mandibular
      arch; instead, in other cases, because of bone and soft tissue biology, general
      healthy state and age of the patient prosthetic management would be better as it
      is less invasive even if less resolutive. For a right tonsillar cavity carcinoma
      the patient, T. F., female, 73-year old, had undergone radical neck dissection
      and hemisection of the homolateral mandible. A guide-device was realized for
      "guiding" the residual mandible into the physiological centric occlusion
      position, and then a removable partial denture was realized as a definitive
      prosthesis. After 3 months therapy the patient was easily able to spontaneously
      reposition the hemimandible itself, also with considerable improvement of the
      masticatory function. Neuromuscular re-education of hemimandibulectomy patients
      via the use of a guide flange on a removable prosthesis applied to the residual
      mandible represents a fundamental condition for permanent prosthetic
      rehabilitation.

PMID- 15263889
TI  - A statistical model for functional mapping of quantitative trait loci regulating
      drug response.
AB  - Differential drug response, that is, pharmacodynamics, is most often likely to be
      a complex trait, controlled by the combined influences of multiple genes and
      environmental influences. Genetic mapping has proven to be a powerful tool for
      detecting and identifying specific genes affecting complex traits, that is,
      quantitative trait loci (QTL), based on polymorphic markers. In this article, we
      present a novel statistical model for genetic mapping of QTL governing
      pharmacodynamic processes. In principle, this model is a combination of
      functional mapping proposed to map function-valued traits and linkage
      disequilibrium mapping designed to provide high-resolution mapping of QTL by
      making use of recombination events created at a historic time. We implement a
      closed-form solution for the Expectation-Maximization algorithm to estimate the
      population genetic parameters of QTL and the simplex algorithm to estimate the
      curve parameters describing the pharmacodynamic changes of different QTL
      genotypes in response to drug dose or concentrations. Extensive simulations are
      performed to investigate the statistical properties of our model. The
      implications of our model in pharmacogenetic and pharmacogenomic research are
      discussed.

PMID- 15263890
TI  - Exploring quality of life following high spinal cord injury: a review and
      critique.
AB  - STUDY DESIGN: Review. OBJECTIVES: To explore the concept of quality of life
      (QOL), critique the practice and problems of assessing QOL following spinal cord
      injury (SCI) and to review the findings of studies into QOL for people with SCI
      both below and above the level of C4. METHODS: Relevant articles were identified
      from the Medline and CINAHL databases for approximately the period 1990-2003,
      cross-indexing 'spinal cord injury' or 'quadriplegia/tetraplegia' with 'quality
      of life', 'life satisfaction', 'social adjustment' or 'psychological adaptation'.
      This search was augmented through papers identified in reference lists. Articles
      were excluded if they were designed solely to examine the impact of a specific
      intervention upon QOL; or if they examined satisfaction with various life domains
      without explicitly linking these to perceptions of QOL. Papers were also accessed
      that addressed the philosophical and epistemological issues involved in QOL
      conceptions and assessment. RESULTS: Review of the literature highlights the
      philosophical and methodological difficulties associated with the quantitative
      measurement of a qualitative experience; and with the assessment of life domains
      chosen by researchers. Analysis of QOL research undertaken among people with all
      levels of SCI demonstrates that dissatisfaction with life following injury arises
      primarily from social disadvantage. However, little research has been conducted
      specifically to ascertain perceptions of QOL among people with high SCI.
      CONCLUSIONS: Ensuring the relevance of future research into QOL following high
      SCI requires qualitative methodology and mixed methods. Further research is
      needed to determine how rehabilitation professionals can act on the findings of
      their QOL assessments and enhance the QOL experienced by people with spinal cord
      injury in the context of their environments. SPONSORSHIP: The early phase of this
      study was supported by: University of British Columbia Graduate Fellowship; Rick
      Hansen Man in Motion Foundation (studentship); Social Sciences and Humanities
      Research Council of Canada: doctoral fellowship.

PMID- 15263891
TI  - Primate brains in the wild: the sensory bases for social interactions.

PMID- 15263892
TI  - Visual objects in context.

PMID- 15263893
TI  - Short-term synaptic plasticity: a comparison of two synapses.

PMID- 15263894
TI  - Pathways to motor incoordination: the inherited ataxias.

PMID- 15263895
TI  - Patenting neuroscience: challenges and opportunities in an interdisciplinary
      field.

PMID- 15263896
TI  - The floating blueprint of hypothalamic feeding circuits.

PMID- 15263897
TI  - Genetic regulation of biological nitrogen fixation.

PMID- 15263898
TI  - The winnowing: establishing the squid-vibrio symbiosis.

PMID- 15263899
TI  - Cell death in planktonic, photosynthetic microorganisms.

PMID- 15263900
TI  - Oncogenic gamma-herpesviruses: comparison of viral proteins involved in
      tumorigenesis.

PMID- 15263901
TI  - Bdellovibrio as therapeutic agents: a predatory renaissance?

PMID- 15263902
TI  - The UK foot-and-mouth disease outbreak - the aftermath.

PMID- 15263903
TI  - Variations in estrogen receptor alpha gene and risk of dementia, and brain
      volumes on MRI.
AB  - The role of estrogens in Alzheimer's disease (AD) is controversial. We
      investigated the association between well-recognized, and potentially functional,
      polymorphisms in the estrogen receptor (ER) alpha gene and the risk of AD in a
      prospective study of 6056 Caucasian older men and women aged 55 years and over.
      In a subset of 468 participants, we assessed volumes of the hippocampus and
      amygdala, which have a high density of ER alpha, with brain magnetic resonance
      imaging (MRI) (1.5 T MR unit). During a total of 35 405 person-years of follow-up
      (mean per persons 5.8 years), 312 new cases of dementia were detected, of whom
      230 were diagnosed with AD. Neither the PvuII nor the XbaI polymorphism or
      haplotypes thereof were associated with the risk of all-cause dementia or AD. In
      contrast, we found that nondemented women who carried the PvuII p allele or
      haplotype 'px' had smaller amygdalar volumes on MRI in an allele-dose-dependent
      fashion. Total amygdalar volume was 4.50 (SE 0.10) in PP genotype, 4.45 (SE 0.06)
      in Pp genotype, and 4.18 ml (SE 0.08) in pp genotype (P trend=0.008). Further
      studies are required to investigate whether this smaller amygdalar volume has
      functional significance.

PMID- 15263904
TI  - Hippocampal alpha5 subunit-containing GABAA receptors modulate the expression of
      prepulse inhibition.
AB  - Prepulse inhibition (PPI) refers to the phenomenon in which a low-intensity
      prepulse stimulus attenuates the reflexive response to a succeeding startle
      eliciting pulse stimulus. The hippocampus, among other structures, is believed to
      play an important role in the modulation of PPI expression. In alpha5(H105R)
      mutant mice, the expression of the alpha5 subunit-containing GABA(A) receptors in
      the hippocampus is reduced. Here, we report that PPI was attenuated, and
      spontaneous locomotor activity was increased in alpha5(H105R) mutant mice. These
      effects were apparent in both genders. Thus, alpha5 subunit-containing GABA(A)
      receptors, which are located extrasynaptically and are thought to mediate tonic
      inhibition, are important regulators of the expression of PPI and locomotor
      exploration. Post-mortem analyses of schizophrenia brains have consistently
      revealed structural abnormalities of a developmental origin in the hippocampus.
      There may be a possibility that such abnormalities include disturbance of alpha5
      GABA(A) receptor function or distribution, given that schizophrenia patients are
      known to exhibit a PPI deficit. Our data further highlight that the potential use
      of alpha5-selective inverse agonists to treat hippocampal-related mnemonic
      dysfunction needs to be considered against the possibility that such compounds
      may be adversely associated with deficient sensorimotor gating.

PMID- 15263905
TI  - Mental and physical distress is modulated by a polymorphism in the 5-HT
      transporter gene interacting with social stressors and chronic disease burden.
AB  - Previous studies have yielded conflicting results as to the putative role of the
      functional polymorphism of the promoter region of the serotonin transporter gene
      (SLC6A4) in the etiology of anxiety-related traits and depressive disorders.
      Recently, a significant gene-environment interaction was found between life
      stressors, the short allele of the SLC6A4 polymorphism and depression. The aim of
      the present study was to investigate if such a gene-environment interaction could
      be replicated within a different population with a different risk structure. A
      total of 1005 subjects from a general population sample (Study of Health in
      Pomerania) were genotyped. Mental and physical distress were assessed on 38 items
      of the modified complaint scale (BL-38). The interaction between the SLC6A4
      genotype, social stressors and chronic diseases with regard to the BL-38 score
      was evaluated by ANOVA. There was no independent association of genotype with
      mental and physical distress. However, significant interactions between genotype,
      unemployment and chronic diseases (F = 6.6; df = 3, 671; P < 0.001) were found in
      females but not in males. The genotype explained 2% of the total variance of the
      BL-38 score and 9.1% of the explained variance. The results partly confirm
      previous findings of a significant gene-environment interaction of the short
      allele, indicating a higher mental vulnerability to social stressors and chronic
      diseases. The relevance of this finding is sustained by the fact that the sample
      characteristics and the risk structure were highly different from previous
      studies.

PMID- 15263906
TI  - Support for the involvement of TPH2 gene in affective disorders.

PMID- 15263907
TI  - Schizophrenia genes, gene expression, and neuropathology: on the matter of their
      convergence.
AB  - This review critically summarizes the neuropathology and genetics of
      schizophrenia, the relationship between them, and speculates on their functional
      convergence. The morphological correlates of schizophrenia are subtle, and range
      from a slight reduction in brain size to localized alterations in the morphology
      and molecular composition of specific neuronal, synaptic, and glial populations
      in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These
      findings have fostered the view of schizophrenia as a disorder of connectivity
      and of the synapse. Although attractive, such concepts are vague, and
      differentiating primary events from epiphenomena has been difficult. A way
      forward is provided by the recent identification of several putative
      susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3,
      and G72). We discuss the evidence for these and other genes, along with what is
      known of their expression profiles and biological roles in brain and how these
      may be altered in schizophrenia. The evidence for several of the genes is now
      strong. However, for none, with the likely exception of COMT, has a causative
      allele or the mechanism by which it predisposes to schizophrenia been identified.
      Nevertheless, we speculate that the genes may all converge functionally upon
      schizophrenia risk via an influence upon synaptic plasticity and the development
      and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate
      transmission may be especially implicated, though there are also direct and
      indirect links to dopamine and GABA signalling. Hence, there is a correspondence
      between the putative roles of the genes at the molecular and synaptic levels and
      the existing understanding of the disorder at the neural systems level.
      Characterization of a core molecular pathway and a 'genetic cytoarchitecture'
      would be a profound advance in understanding schizophrenia, and may have equally
      significant therapeutic implications.

PMID- 15263908
TI  - Failure to confirm association between AKT1 haplotype and schizophrenia in a
      Japanese case-control population.

PMID- 15263909
TI  - Flow cytometric analysis of normal and reactive spleen.
AB  - Spleen is surgically removed for both non-neoplastic and neoplastic pathologies.
      A significant proportion of splenectomy specimens require distinguishing between
      reactive and neoplastic conditions (eg lymphoma). To establish a 'normal'
      reference range for the spleen lymphocyte subsets, fresh samples of benign,
      reactive spleens obtained from adult patients (N=12) and samples of normal spleen
      obtained from cadaveric transplant donors (N=14) were analyzed using three- and
      four-color flow cytometry. Study of pan-B, -T, and -NK marker expression revealed
      that the frequency of T cells is higher and that of B cells is lower in reactive
      (non-neoplastic) compared to normal (cadaveric) spleen. Furthermore, our study
      established a frame of reference for cell markers commonly used for
      immunophenotyping of lymphoma, and identified discrete lymphocyte subsets, such
      as early plasma cells and T cells carrying the phenotype of the NK/T subset.
      These results will facilitate an accurate interpretation of the flow cytometric
      analysis of human spleen lymphocytes.

PMID- 15263910
TI  - CD117 expression in mesothelioma.

PMID- 15263920
TI  - Aerobic fitness, physiologic difficulty and physical activity in Black and White
      women.
AB  - PURPOSE: The purpose of this work was to determine if racial differences in
      maximum oxygen uptake (VO(2) max) and difficulty in doing submaximum (sub)
      exercise tasks contribute to activity-related energy expenditure (AEE) and
      activity-related time equivalent (ARTE) index, an index of time spent in physical
      activity. METHODS: Subjects were 35 Black and 39 White sedentary premenopausal
      women group matched for age, weight and body composition. Percent fat was
      determined by dual energy X-ray absorptiometry, AEE by doubly labeled water and
      sleeping energy expenditure, ARTE index by AEE and energy cost above sleeping for
      five exercise tasks, and VO(2) max by a graded exercise test. Subexercise oxygen
      uptake was measured during walking at 3 mph on the flat and up a 2.5% grade,
      climbing stairs, and riding a bike ergometer at 50 W. Difficulty of exercise was
      assessed during the subexercise and taken as heart rate, ventilation, and ratings
      of perceived exertion (RPE) and expressed as a % of the individual's maximum.
      RESULTS: VO(2) max was related to AEE (r=0.29, P<0.04) and to ARTE index (r=0.37,
      P<0.01). All three difficulty measures were related to AEE (r=-0.35 to -0.42, P
      values<0.02) and the ARTE index (r=-0.49 to -0.52, all P-values<0.01), with the
      exception of RPE with ARTE (r=-0.27, P=0.10). Compared to Black women, White
      women had significantly higher VO(2) max (12%), AEE (45%) and ARTE (50%), and
      significantly less physiologic difficulty of performing the subexercise tasks:
      heart rate (5%), ventilation (13%), and RPE (8%). Significant racial differences
      in AEE and ARTE disappeared after adjusting for any of the three difficulty
      measures. CONCLUSIONS: These results show that more participation in free-living
      physical activity is related to greater VO(2) max and less difficulty in being
      active. In addition, lower levels of physical activity found in Black women may
      be partially explained by lower VO(2) max and increased difficulty of engaging in
      physical activities.

PMID- 15263921
TI  - Pretreatment predictors of attrition and successful weight management in women.
AB  - OBJECTIVE: This study analyzed baseline behavioral and psychosocial differences
      between successful and nonsuccessful participants in a behavioral weight
      management program. Success was defined by commonly used health-related criteria
      (5% weight loss). Noncompletion was also used as a marker of a failed attempt at
      weight control. SUBJECTS: A total of 158 healthy overweight and obese women (age,
      48.0+/-4.5 y; BMI, 31.0+/-3.8 kg/m(2); body fat, 44.5+/-5.3%). INTERVENTION:
      Subjects participated in a 16-week lifestyle weight loss program consisting of
      group-based behavior therapy to improve diet and increase physical activity, and
      were followed for 1 y after treatment. METHODS: At baseline, all women completed
      a comprehensive behavioral and psychosocial battery assessing dieting/weight
      history, dietary intake and eating behaviors, exercise, self-efficacy, outcome
      evaluations, body image, and other variables considered relevant for weight
      management. Participants who maintained a weight loss of 5% or more at 16 months
      (or 10% or more of initial fat mass) were classified as successful. Nonsuccessful
      participants were those who dropped out and completers who had not lost weight at
      follow-up. RESULTS: Of all participants, 30% (n=47) did not complete initial
      treatment and/or missed follow-up assessments (noncompleters). Noncompletion was
      independently associated with more previous weight loss attempts, poorer quality
      of life, more stringent weight outcome evaluations, and lower reported
      carbohydrate intake at baseline. In logistic regression, completion status was
      predicted correctly in 84% of all cases (chi(2)=45.5, P<0.001), using baseline
      information only. Additional predictors of attrition were initial weight,
      exercise minutes, fiber intake, binge eating, psychological health, and body
      image. A large variation in weight loss/maintenance results was observed (range:
      37.2 kg for 16-month weight change). Independent baseline predictors of success
      at 16 months were more moderate weight outcome evaluations, lower level of
      previous dieting, higher exercise self-efficacy, and smaller waist-to-hip ratio.
      Success status at follow-up was predicted correctly in 74% of all starting cases
      (chi(2)=33.6, P<0.001). CONCLUSION: Psychosocial and behavioral variables (eg,
      dieting history, dietary intake, outcome evaluations, exercise self-efficacy, and
      quality of life) may be useful as pretreatment predictors of success level and/or
      attrition in previously overweight and mildly obese women who volunteer for
      behavioral weight control programs. These factors can be used in developing
      readiness profiles for weight management, a potentially important tool to address
      the issue of low success/completion rates in the current management of obesity.

PMID- 15263922
TI  - Association of weight change, weight control practices, and weight cycling among
      women in the Nurses' Health Study II.
AB  - OBJECTIVE: To assess the association of weight cycling with weight change, weight
      control practices, and bulimic behaviors. METHODS: A nested study of 2476 young
      and middle-aged women in the Nurses' Health Study II who provided information on
      intentional weight losses between 1989 and 1993. SAMPLE: In total, 224 women who
      were severe cyclers, 741 women who were mild cyclers, 967 age- and BMI-matched
      controls (noncyclers), and 544 women who did not weight cycle and maintained
      their weight between 1989 and 1993 completed a questionnaire in 2000-2001
      assessing recent intentional weight losses, weight control practices, and weight
      concerns. RESULTS: After controlling for age and body mass index (BMI) in 1993,
      when weight cycling was initially assessed, mild cyclers gained an average of 6.7
      pounds (lbs) more and severe cyclers gained approximately 10.3 lbs more than
      noncyclers between 1993 and 2001. Weight cyclers preferred to change their diet
      rather than to exercise to control their weight. Severe weight cyclers were less
      likely than noncyclers to use frequent exercise as a weight control strategy
      (odds ratio [OR]=0.8, 95% confidence interval (CI) 0.6-1.1). Cyclers were also
      more likely than noncyclers to engage in binge eating (mild cyclers: OR=1.8, 95%
      CI 1.4-2.4; and severe cyclers: OR=2.5, 95% CI 1.7-3.5). Independent of weight
      cycling status, age, and BMI, women who engaged in binge eating gained
      approximately 5 lbs more than their peers (P<0.001). CONCLUSIONS: Weight cycling
      was associated with greater weight gain, less physical activity, and a higher
      prevalence of binge eating. Low levels of activity and binge eating may be
      partially responsible for the large amount of weight regained by weight cyclers.

PMID- 15263923
TI  - Left ventricular hypertrophy and QT interval in obesity and in hypertension:
      effects of weight loss and of normalisation of blood pressure.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) and prolonged QT interval at ECG
      (QTc) are common in both obesity and arterial hypertension (AH), and are risk
      factors for cardiovascular disease and sudden death. METHODS: We compared the
      frequencies of LVH (ECG criteria) and QTc in obese-AH (n=41), in normotensive
      obese (n=75), in lean-AH (n=30), and in lean controls (n=68) comparable for age
      and sex; in obese patients, LVH and QTc were evaluated under basal conditions and
      1 y later, that is, after a significant weight loss induced by bariatric surgery.
      RESULTS: LVH was more frequent, and QTc was longer, in obese-AH, in normotensive
      obese, and in lean-AH than in lean controls; after weight loss, frequency of LVH
      decreased in obese subjects becoming normotensive (n=87), not in obese subjects
      remaining hypertensive (n=29), while QTc decreased in all obese subjects.
      CONCLUSION: Weight loss can effectively reduce QTc; when concomitant AH
      disappears, weight loss can also reduce the prevalence of LVH. In obese patients
      remaining hypertensive, aggressive pharmacological treatment is therefore
      indicated to correct LVH.

PMID- 15263925
TI  - Ligand-free Heck reactions using low Pd-loading.
AB  - Activated and non-activated aryl bromides undergo smooth ligand-less Heck
      reactions, provided low amounts of palladium salts such as Pd(OAc)2 are used
      (ideally 0.01-0.1 mol%). This industrially viable process appears to involve
      palladium nanoparticles.

PMID- 15263924
TI  - Body fat distribution of overweight females with a history of weight cycling.
AB  - Weight cycling may cause a redistribution of body fat to the upper body fat
      compartments. We investigated the distribution of subcutaneous adipose tissue
      (SAT) in 30 overweight women with a history of weight-cycling and age-matched
      controls (167 normal weight and 97 overweight subjects). Measurements of SAT were
      performed using an optical device, the Lipometer. The SAT topography describes
      the thicknesses of SAT layers at 15 anatomically well-defined body sites from
      neck to calf. The overweight women with a history of weight cycling had
      significantly thicker SAT layers on the upper body compared to the overweight
      controls, but even thinner SAT layers on their legs than the normal weight women.
      An android fat pattern was attributed to overweight females and, even more
      pronounced, to the weight cyclers. The majority of normal weight women showed a
      gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight
      cyclers and overweight controls could be classified correctly into the two
      groups. These findings show the importance of normal weight maintenance as a
      health-promoting factor.

PMID- 15263926
TI  - Perylene bisimide dyes as versatile building blocks for functional supramolecular
      architectures.
AB  - Perylene bisimide dyes and their organization into supramolecular architectures
      through hydrogen-bonding, metal ion coordination and pi-pi-stacking is discussed;
      further self-assembly leading to nano- and meso-scopic structures and liquid
      crystalline compounds is also addressed.

PMID- 15263927
TI  - Supramolecular assembly of ligand-directed triangular [Cu(II)3Cl] clusters with
      spin frustration and spin-chain behaviour.
AB  - Triangular [Cu(II)3Cl] clusters, containing a chloro ligand in an unprecedented
      trigonal planar coordination mode, are assembled in a 3-D array by the
      combination of coordinative and hydrogen-bonded interactions, which result in
      magnetically isolated 1-D chains exhibiting a combination of spin frustration and
      spin-chain behaviour.

PMID- 15263928
TI  - Fullerohelicates: a new class of fullerene-containing supermolecules.
AB  - A multicomponent array made of a bis-copper(I) helicate core and two peripheral
      fullerene subunits has been prepared and electron transfer from the photoexcited
      Cu(I)-complexed unit to C60 occurs.

PMID- 15263929
TI  - Shape control of anatase TiO2 nanoparticles by amino acids in a gel-sol system.
AB  - Ellipsoidal anatase TiO2 nanoparticles of different aspect ratios were obtained
      by the gel-sol method in the presence of amino acids in which the resulting
      particles were basically single crystals, but highly rough surfaces or partly
      polycrystalline structures were observed with a high concentration of glutamic
      acid or aspartic acid.

PMID- 15263930
TI  - Heterogeneous catalysis of a coordination network: cyanosilylation of imines
      catalyzed by a Cd(II)-(4,4'-bipyridine) square grid complex.
AB  - A coordination network prepared from Cd(NO3)2 and 4,4'-bipyridine (4,4'-bpy)
      catalyzed the cyanosilylation of imines under heterogeneous conditions.

PMID- 15263931
TI  - Luminescent homochiral silver(I) lamellar coordination networks built from
      helical chains.
AB  - The reactions of 2,2'-dimethoxy-1,1'-binaphthyl-3,3'-bis(4-vinylpyridine)(L) with
      AgNO3 or AgClO4 at 70 degrees C gave rise to two novel luminescent homochiral
      lamellar coordination polymers, AgL2X (X = NO3- for 1 or ClO4- for 2), which are
      built from linking helical chains by Ag(I) atoms as hinges.

PMID- 15263932
TI  - Synthesis, crystal structure and electrochemical properties of
      bis(ethylenedioxy)tetraselenafulvalene (BEDO-TSeF).
AB  - Bis(ethylenedioxy)tetraselenafulvalene (BEDO-TSeF) has been synthesized using
      elemental selenium as the only source of the selenium atoms, and its crystal
      structure and electrochemical properties are examined and compared with its
      sulfur analogues.

PMID- 15263933
TI  - Effects of the alkali metal counter ions on the germanium-germanium double bond
      length in a heavier group 14 element ethenide salt.
AB  - The first, well-characterized 1,2-dilithium salt of a group 14 element ethenide
      species, [[(dioxane)(0.5)(Et2O)LiGeC6H3-2,6-Mes2]2]infinity, shows that the
      positions of the cations have a large effect on the length of the Ge-Ge double
      bond.

PMID- 15263934
TI  - Three-dimensional metal-organic framework with (3,4)-connected net, synthesized
      from an ionic liquid medium.
AB  - A new 3D metal-organic framework with a (3,4)-connected network topology is
      synthesized from an ionic liquid medium; its highly symmetrical structure
      comprises doubly interpenetrating nets with the cubic-C3N4 topology.

PMID- 15263935
TI  - A supramolecular nematic phase in sulfonated polyaramides.
AB  - A water-soluble polyaramide "sulfo-invert-PPTA" surprisingly, already at a
      molecular weight of 10,000 g mol(-1), exhibits a nematic liquid crystalline phase
      in water at very low polymer concentrations, around 1-2wt%, indicating that
      supramolecular assemblies of molecules are the building blocks of the nematic
      phase.

PMID- 15263936
TI  - A new type of oxygen bridged Cu(II)36 aggregate formed around a central [KCl6]5-
      unit.
AB  - A magnetically coupled Cu(II)36 aggregate forms around a potassium chloride unit.

PMID- 15263937
TI  - Inclusion of gold nanoparticles into a discotic liquid crystalline matrix.
AB  - The thermophysical properties of mixtures of hexanethiolate-capped gold
      nanoparticles and three types of discotic liquid crystals, investigated using
      polarizing optical microscopy, differential scanning calorimetry and DC
      conductivity, indicate inclusion of gold nanoparticles into a matrix of
      triphenylene-based discotic liquid crystals.

PMID- 15263938
TI  - Enantioselective formal synthesis of uleine alkaloids from phenylglycinol-derived
      bicyclic lactams.
AB  - A two-step route for the enantioselective construction of the tetracyclic ring
      system of uleine alkaloids, involving the stereoselective conjugate addition of
      an appropriate indole-containing nucleophile to a chiral bicyclic delta-lactam
      and the subsequent cyclization on the indole 3-position of the resulting 4,5
      disubstituted 2-piperidone, has culminated in the formal total synthesis of
      several alkaloids of this group.

PMID- 15263939
TI  - Fabrication of large-scale zinc oxide ordered pore arrays with controllable
      morphology.
AB  - The fabrication of large-scale ZnO ordered pore arrays by the potentiostatic
      electrochemical deposition method based on a two-dimensional ordered colloidal
      monolayer template is reported. The pore morphology evolves from hemispherical to
      a well-like structure by controlling the deposition potential.

PMID- 15263940
TI  - Fabrication and electrocatalytic properties of polyaniline/Pt nanoparticle
      composites.
AB  - Polyaniline (PANI)/Pt nanoparticle composites can be prepared by the spontaneous
      redox reaction of K2PtCl4 with PANI, to yield thin films that show
      electrocatalytic properties in both acidic and neutral aqueous media.

PMID- 15263941
TI  - Synthesis of novel dendrimer-like star block copolymers with definite numbers of
      arms by combination of ROP and ATRP.
AB  - Well-defined biodegradable dendrimer-like star block copolymers with up to 24
      arms were successfully synthesized by combination of living ring-opening
      polymerization (ROP) and atom transfer radical polymerization (ATRP) on the basis
      of dendritic benzyl alcohols.

PMID- 15263942
TI  - Mononuclear precursor for MOCVD of HfO2 thin films.
AB  - We report the precursor characteristics of a novel mononuclear mixed alkoxide
      compound [Hf(O(i)Pr)2(tbaoac)2] and its application towards MOCVD of HfO2 thin
      films in a production tool CVD reactor.

PMID- 15263943
TI  - Asymmetric lithium(I) and copper(II) alkoxy-N-heterocyclic carbene complexes;
      crystallographic characterisation and Lewis acid catalysis.
AB  - A one-pot synthesis of a wide range of bidentate, alkoxide-N-heterocyclic carbene
      ligands provides new lithium alkoxy-carbenes and a range of covalently bound
      organometallic Cu(II) carbene complexes, which are catalytically active, in some
      cases enantioselectively, for conjugate addition reactions.

PMID- 15263944
TI  - Self-immolative dendrimer biodegradability by multi-enzymatic triggering.
AB  - New self-immolative dendritic molecules have been designed and synthesized. The
      dendrons are built with a multi-enzymatic triggering mechanism, which initiates
      their biodegradation through a self-immolative chain fragmentation to release a
      reporter group from the focal point. The dendritic backbone is constructed from
      polycarbamate linkages, which are stable to hydrolysis and enhance the dendrons'
      solubility in water. The degradation can readily take place under physiological
      conditions on enzymatic triggering.

PMID- 15263945
TI  - Asymmetric aziridination of chalcones catalyzed by a novel backbone 1,8
      bisoxazolinylanthracene (AnBOX)-copper complex.
AB  - Highly enantioselective aziridination of chalcones catalyzed by a novel backbone
      1,8-bisoxazolidinylanthracene (AnBOX) and CuOTf with up to >99% ee and the
      opposite enantioselectivity compared with the ligands of Evans are described.

PMID- 15263946
TI  - Reaction of gold(III) oxo complexes with alkenes. Synthesis of unprecedented gold
      alkene complexes, [Au(N,N)(alkene)][PF6]. Crystal structure of [Au(bipy(ip))(eta2
      CH2=CHPh)][PF6] (bipy(ip) = 6-isopropyl-2,2'-bipyridine).
AB  - Gold alkene complexes [Au(bipyR)(eta2-alkene)][PF6] (bipyR = 6-alkyl-2,2'
      bipyridine) have been obtained by reaction of gold(III) oxo complexes
      [Au2(bipyR)2(mu-O)2][PF6]2 with alkenes. The crystal structure of the styrene
      adduct [Au(bipy(ip))(eta2-CH2=CHPh)][PF6] (bipy(ip) = 6-isopropyl-2,2'
      bipyridine) has been solved by X-ray analysis.

PMID- 15263947
TI  - Ruthenium catalyzed addition reaction of carboxylic acid across olefins without
      beta-hydride elimination.
AB  - The cationic ruthenium catalyst (Cp*RuCl2)2/AgOTf/Ligand promotes the addition
      reaction of carboxylic acids across olefins without beta-hydride elimination.

PMID- 15263948
TI  - Chiral (salen)Co(III) catalyst for the synthesis of cyclic carbonates.
AB  - A catalyst system comprised of a Co(III)(salen) complex and a Lewis base is
      investigated for the reaction of CO2 and a variety of epoxides to form cyclic
      carbonates. Application of this catalyst system in the kinetic resolution of
      propylene oxide is also discussed.

PMID- 15263949
TI  - New flavin and deazaflavin oligonucleotide conjugates for the amperometric
      detection of DNA hybridization.
AB  - The functionalization of an oligonucleotide by flavin and deazaflavin derivatives
      allowed an amperometric determination of the hybridization process through the
      disappearance of the electroactivity of the free oligonucleotide and the
      appearance of a new electrochemical signal characteristic of the resulting
      duplex.

PMID- 15263950
TI  - STM-based molecular detection of "catch-and-release" of protons for bipyridine
      bound to phenylene-ethynylene thiol.
AB  - The protonation/deprotonation response of a novel bipyridine containing
      (phenylene-ethynylene) thiol adsorbed to a Au surface was investigated with
      scanning tunneling microscopy (STM), showing reversible changes in the average
      heights (approximately 50 spots) and the height distribution arising from
      protonation/deprotonation.

PMID- 15263951
TI  - Oxidation-resistant, sterically demanding phenanthrolines as supporting ligands
      for copper(I) nitrene transfer catalysts.
AB  - New 1,10-phenanthroline ligands have been synthesized with C6F5- or 2,4,6
      (CF3)3C6H2- groups in the 2- and 9-positions; a cationic copper(I) complex of the
      latter catalyses nitrene transfer to the C-H bonds of electron-rich arenes.

PMID- 15263952
TI  - One-pot aerosol synthesis of ordered hierarchical mesoporous core-shell silica
      nanoparticles.
AB  - A mixed surfactant approach has been successfully employed in an aerosol-based
      synthesis of spherical silica particles exhibiting a new core-shell structure
      where the shell and the core exhibit different ordered mesoporosity and pore
      sizes.

PMID- 15263953
TI  - Possible insights into metal ion recognition in calcium-binding proteins provided
      by complexing properties of ligands containing amide oxygen donors.
AB  - The formation constants of the ligand N,N,N',N'-tetrakis(carbamoylmethyl)
      ethylenediamine suggest that the amide oxygen is a stronger Lewis base in water
      than the alcoholic oxygen, or water, and that part of the selectivity for Ca2+
      over Mg2+ shown by calcium-binding proteins such as calmodulin or annexin may be
      due to the higher affinity of Ca2+ for the O-donor of the Ca-binding amide groups
      present in such proteins.

PMID- 15263954
TI  - Multienzyme system for dihydroxyacetone phosphate-dependent aldolase catalyzed C
      C bond formation from dihydroxyacetone.
AB  - A multienzyme system composed by recombinant dihydroxyacetone kinase from
      Citrobacter freundii, fuculose-1-phosphate aldolase and acetate kinase, allows a
      practical one-pot C-C bond formation catalysed by dihydroxyacetone phosphate
      dependent aldolases from dihydroxyacetone and an aldehyde.

PMID- 15263955
TI  - On the importance of steady-state isotopic techniques for the investigation of
      the mechanism of the reverse water-gas-shift reaction.
AB  - The formation and reactivity of surface intermediates in the reverse water-gas
      shift reaction on a Pt/CeO2 catalyst are critically dependent on the reaction
      conditions so that conclusions regarding the reaction mechanism cannot be
      inferred using ex operando conditions.

PMID- 15263956
TI  - Iridium-catalyzed coupling of simple primary or secondary amines, aldehydes and
      trimethylsilylacetylene: preparation of propargylic amines.
AB  - The coupling of amines, aldehydes and trimethylsilylacetylene was found to be
      promoted in the presence of a catalytic amount of [IrCl(cod)]2; 1 : 1 : 1 or 1 :
      2 : 2 coupling products were obtained by allowing primary amine to react with
      aldehyde and trimethylsilylacetylene.

PMID- 15263957
TI  - Synthesis and structural characterisation of the first bis(bora)calixarene: a
      selective, bidentate, fluorescent fluoride sensor.
AB  - A bis(bora)calixarene 3, the first lower-rim boron derivatised calixarene to be
      structurally characterised, is synthesised by the reaction of PhBCl2 with 4-tert
      butylcalix[4]arene, and is demonstrated to be a sensitive and selective
      fluorescent fluoride sensor.

PMID- 15263958
TI  - The influence of metal loading and pH during preparation on the CO oxidation
      activity of Au/TiO2 catalysts.
AB  - Au/TiO2 catalysts with gold loadings in the range 0.06-1.9 wt.%, prepared by
      'deposition-precipitation' at pH 9, have a constant and high specific activity
      for the oxidation of CO: 3.9(+/- 0.4) x 10(-4) molCO s(-1) gAu(-1) at 243 K.

PMID- 15263959
TI  - Neutral and ionic dissociation patterns in hexacoordinate silicon chelates: a
      model nucleophilic substitution at pentacoordinate silicon.
AB  - A model nucleophilic-displacement reaction coordinate at pentacoordinate silicon
      is demonstrated by neutral and ionic dissociation equilibria through a stable
      hexacoordinate complex.

PMID- 15263960
TI  - Preparation of novel nano-composite Ni(OH)2/USY material and its application for
      electrochemical capacitance storage.
AB  - A novel nano-composite material of Ni(OH)2/USY was prepared in our lab. This
      nanostructure creates electrochemical accessibility of electrolyte OH- ions to
      Ni(OH)2 thin layers and a fast diffusion rate within the redox phase.

PMID- 15263961
TI  - Direct propylene epoxidation on chemically reduced Au nanoparticles supported on
      titania.
AB  - A highly selective titania supported propylene epoxidation catalyst was
      synthesized from chemically reduced, thiol capped, gold nanoparticles, and
      characterized by TEM and XPS.

PMID- 15263962
TI  - Using micelles for a new approach to fluorescent sensors for metal cations.
AB  - A new approach based on self-assembly inside micelles has been individuated to
      prepare a system behaving as a water-operating selective fluorescent sensor for
      Cu2+ and Ni2+.

PMID- 15263963
TI  - Pressure control of diastereodifferentiating [2 + 2] photocycloaddition of (E)
      stilbene to chiral fumarate upon direct and charge-transfer excitation.
AB  - The geometry (donor-acceptor distance) and association constant of the ground
      state CT complex were considerably affected by applied pressure, thus enhancing
      the reaction rate and the adduct yield particularly upon CT excitation, but the
      diastereoselectivity did not show any substantial change at elevated pressures in
      both excitation modes.

PMID- 15263964
TI  - First planar chiral bidentate ligand based on a (eta5-cyclopentadienyl)(eta4
      cyclobutadiene) cobalt backbone: high efficiency in enantioselective palladium
      catalyzed allylic substitutions.
AB  - The synthesis of the planar chiral (R)-[eta5-(1-diphenylphosphino-2-tert
      butylsulfenyl)cyclopentadienyl](eta4-tetraphenylcyclobutadiene) cobalt and its
      high efficiency as P,S-bidentate ligand in Pd-catalyzed allylic substitutions is
      described.

PMID- 15263965
TI  - Magnetophoretic detection of photo-induced spin transition.
AB  - Magnetophoretic velocimetry detected the spin transition of a single Co-Fe
      Prussian Blue analogous micro-crystal in water induced by a single-shot pulse
      laser.

PMID- 15263966
TI  - A new fluoride selective electrochemical and fluorescent chemosensor based on a
      ferrocene-naphthalene dyad.
AB  - A new difunctionalized receptor based on an aza-ferrocenophane structure shows
      electrochemical and fluorescent responses to fluoride anion.

PMID- 15263967
TI  - Synthesis of amorphous mesoporous aluminophosphate materials with high thermal
      stability using a citric acid route.
AB  - Amorphous mesoporous aluminophosphate materials synthesized from precursors of
      Al(NO3)3/H3PO4/NH4OH in the presence of citric acid, exhibit high specific
      surface areas, narrow pore size distributions and excellent thermal stabilities.

PMID- 15263968
TI  - Dye-sensitized nanocrystalline solar cells based on composite polymer
      electrolytes containing fumed silica nanoparticles.
AB  - We report remarkably high energy conversion efficiency (4.5% at 100 mW cm(-2)) of
      a dye-sensitized solar cell in the solid state, using composite polymer
      electrolytes containing fumed silica nanoparticles.

PMID- 15263969
TI  - Nanotubes of poly(phenylene vinylene) derivative at the air/water interface.
AB  - Different sizes of nanotubes of poly(2-methoxy-5-(n-hexadecyloxy)-p-phenylene
      vinylene)(MH-PPV) have been fabricated at the air/water interface by compressing
      a monolayer of MH-PPV beyond its collapse point, and their structural
      characteristics were studied by means of TEM, AFM, SAXRD, IRRAS.

PMID- 15263970
TI  - Dianionic and trianionic macrocycles in cobalt N-confused porphyrin complexes.
AB  - We report the syntheses of cobalt N-confused porphyrins; this work completes the
      series of the late first-row transition metals that have been incorporated into
      the core of N-confused porphyrin, and in these compounds the macrocycles can act
      as either a -2 or -3 anion.

PMID- 15263971
TI  - Novel chromium(VI) catalyzed oxidation of N-alkylamides to imides with periodic
      acid.
AB  - A novel and practical procedure for preparation of imides is described using
      chromium(VI) oxide to catalyze the oxidation of N-alkylamides with periodic acid
      in the presence of acetic anhydride in acetonitrile.

PMID- 15263972
TI  - Synthesis and photocatalytic properties of highly crystalline and ordered
      mesoporous TiO2 thin films.
AB  - Highly crystalline and ordered mesoporous TiO2 thin films have been synthesized
      by stabilization of the mesostructure with confined carbon; the films exhibit
      2.5% photoconversion efficiency for the water photolysis at zero-bias and Xe lamp
      illumination of 40 mW cm(-2).

PMID- 15263973
TI  - Photosensitized oxygenation of diaryl tellurides to telluroxides and their
      oxidizing properties.
AB  - Photosensitized oxidation of tellurides carrying bulky aromatic substituents
      afforded the corresponding telluroxides which were found to react with simple
      alcohols to give the corresponding carbonyl compounds in excellent yields along
      with the starting tellurides.

PMID- 15263974
TI  - A novel and template-free method for the spontaneous formation of aluminosilicate
      macro-channels with mesoporous walls.
AB  - A simple and template-free synthesis pathway was developed leading to
      hierarchical meso-macroporous aluminosilicates made of an assembly of macro
      channels with openings between 0.5 and 2.0 microm and mesoporous walls.

PMID- 15263975
TI  - The difficult and slow inclusion of violence on the health sector agenda.

PMID- 15263976
TI  - [The importance of family in drug abuse treatment: a literature review].
AB  - This article presents a literature review on family and two phases of drug
      addiction treatment: engagement and treatment itself. Referring to various
      studies, the article highlights the need for addicts to be treated together with
      their families in order to achieve satisfactory results. The study points to
      important socio-cultural issues that influence institutional treatment and
      emphasizes that treatment of addicts and their families fosters an understanding
      and basis for effective preventive action.

PMID- 15263977
TI  - The concept and measurement of race and their relationship to public health: a
      review focused on Brazil and the United States.
AB  - Race has been widely used in studies on health and healthcare inequalities,
      especially in the United States. Validity and reliability problems with race
      measurement are of concern in public health. This article reviews the literature
      on the concept and measurement of race and compares how the findings apply to the
      United States and Brazil. We discuss in detail the data quality issues related to
      the measurement of race and the problems raised by measuring race in multiracial
      societies like Brazil. We discuss how these issues and problems apply to public
      health and make recommendations about the measurement of race in medical records
      and public health research.

PMID- 15263978
TI  - [Knowledge and opinions concerning legal and ethical issues with abortion among
      physicians working in emergency wards in Ribeirao Preto, Sao Paulo, Brazil].
AB  - This study focused on the knowledge and opinions of physicians regarding legal
      and ethical aspects of abortion. A self-administered questionnaire was filled out
      by 57 physicians working in the emergency rooms of two hospitals in Ribeirao
      Preto, Sao Paulo State, Brazil in 2001. The questionnaire had 38 questions on
      general knowledge, legislation, and attitudes towards abortion. Interviewees'
      mean age was 28.3, most were females, 52.6% were single, 42.1% were married,
      54.4% were Catholic, and 21% were Spiritists. Although most of the physicians had
      a good level of overall knowledge on abortion (70%), one in five was not aware
      that abortion is the main cause of maternal mortality in Brazil. Most accepted
      the prevailing legal conditions for performing an abortion in Brazil but would
      also include fetal malformation incompatible with life, while opposing
      decriminalization of abortion on other grounds. Limited knowledge is revealed by
      misconceptions concerning enforcement of the prevailing legislation in practice.
      The study strongly suggests that many physicians lack knowledge or face
      difficulties in conforming to the Brazilian legislation on abortion.

PMID- 15263979
TI  - [The relationship between oral habits, oronasopharyngeal alterations, and
      malocclusion in preschool children in Vitoria, Espirito Santo, Brazil].
AB  - The objective of this study was to estimate the prevalence of malocclusion and
      associated variables such as deleterious habits (DH) and oronasopharyngeal
      alterations (OA), mouth breathing, atypical phonation, and atypical swallowing in
      three-year-old children in Vitoria, Espirito Santo State, Brazil. The sample
      included 291 children of both sexes enrolled in a Children's Educational Center
      and selected through probability sampling by conglomerates. Logistic regression
      indicated a high relative risk (RR) in children with altered overjet, open bite,
      and cross-bite to present mouth breathing (RR = 1.89; CI: 1.56-2.03), (RR = 2.46;
      CI: 2.00-3.02), (RR = 1.45; CI: 1.23-1.72); atypical swallowing (RR = 2.57; CI:
      1.87-3.52), (RR = 3.49; CI: 2.53-4.81), (RR = 1.86; CI: 1.46-2.39); and atypical
      phonation (RR = 2.25; CI: 1.66-3.05), (RR = 3.18; CI: 2.38-4.25), (RR = 1.71; CI:
      1.32-2.22), respectively. An association was shown between finger or pacifier
      sucking and altered overjet (p < 0.001), and between pacifier sucking and open
      bite (p < 0.001). Such results indicate that the prevalence of malocclusions is
      associated with DH and OA.

PMID- 15263980
TI  - [Dietary and physical activity factors as determinants of the increase in
      overweight/obesity in Brazil].
AB  - Data from Brazilian national surveys conducted since the 1970s have indicated an
      increase in the prevalence of overweight/obesity. The two most frequently cited
      causes of this trend have been dietary changes and reduction in physical
      activity, characterizing a "contemporary Western lifestyle". The objective of
      this paper is to identify and assess some indicators associated with changes in
      eating habits and physical activity patterns in the Brazilian population in the
      last 30 years. Despite the lack of detailed data, the following factors appear to
      play an important role in the process: internal migration; dining out; increased
      consumption of fast food; labor changes; transportation; and the use of home
      appliances. More information on dietary and physical activity patterns in
      association with anthropometric data on the Brazilian population are needed for a
      better understanding of each factor's role in these relationships. Meanwhile,
      inter-sector programs and projects with well-defined targets and outcomes are
      needed for the population's adherence to a healthier lifestyle, in order to
      control the increase in overweight/obesity.

PMID- 15263981
TI  - [Quality of the environment and associated factors: a pediatric study in Pelotas,
      Rio Grande do Sul, Brazil].
AB  - This study aims to describe and identify factors associated with environmental
      quality and characteristics of children exposed to environmental risk factors in
      Pelotas, Rio Grande do Sul, Brazil. This was a prospective, population-based
      study, including 630 children from the 1993 birth cohort. During the year 1998,
      environmental quality and other information were assessed using the Home
      Observation for the Measurement of the Environment. Data were submitted to
      univariate analysis. The association between the variables and the outcome was
      evaluated through prevalence ratios, 95% confidence intervals, and chi-square.
      Logistic regression was performed according to a hierarchical model. Some 97
      children (15%) were living in negative environments. Eight risk factors were
      associated with environmental quality: low monthly family income, low maternal
      schooling, male gender, households with more than 7 members, 4 or more siblings,
      tobacco use during gestation, children sleeping in their parents' bed at age 4
      years, and mothers with psychiatric disorders.

PMID- 15263982
TI  - [Heath education on osteoporosis for elderly university students].
AB  - The purpose of this study was to analyze knowledge and concepts in relation to
      osteoporosis and changes in eating habits among elderly university students
      before and after an educational intervention. An action-based research strategy
      applied questionnaires to 95 individuals ranging in age from 60 to 86 years, with
      or without osteoporosis. The work showed an obvious lack of knowledge concerning
      important information about the disease and measures needed to better control
      progressive loss of bone mass. After four months of educational activities, more
      than half of the group had reported dietary changes. We emphasize the need to
      adopt educational strategies not only to inform on ideal preventive practices for
      osteoporosis but also to build a new mindset and behavior, which are important to
      control this condition.

PMID- 15263983
TI  - [Geostatistical modeling of Ascaris lumbricoides infection].
AB  - The following study intends to model the spatial distribution of ascariasis,
      through the use of geoprocessing and geostatistic analysis. The database used in
      the study was taken from the PAISQUA project, including a coproparasitologic and
      domiciliary survey, conducted in 19 selected census tracts of Rio de Janeiro
      State, Brazil, randomly selecting a group of 1,550 children aged 1 to 9 years old
      plotting them in their respective domicile's centroids. Risk maps of Ascaris
      lumbricoides were generated by indicator kriging. The estimated and observed
      values from the cross-validation were compared using a ROC curve. An isotropic
      spherical semivariogram model with a range of 30m and nugget effect of 50% was
      employed in ordinary indicator kriging to create a map of probability of A.
      lumbricoides infection. The area under the ROC curve indicated a significant
      global accuracy. The occurrence of disease could be estimated in the study area,
      and a risk map was elaborated through the use ordinary kriging. The spatial
      statistics analysis has proven itself adequate for predicting the occurrence of
      ascariasis, unrestricted to the regions political boundaries.

PMID- 15263984
TI  - [Eco-epidemiology of cutaneous leishmaniasis in Buriticupu, Amazon region of
      Maranhao State, Brazil, 1996-1998].
AB  - This study presents the distribution of leishmaniasis in the town of Buriticupu,
      Maranhao, Brazil, by month, season, occupation, gender, and age from 1996 to
      1998. These data were compared with those on sand flies obtained by other authors
      during the same period. The disease affected all age groups, in the following
      order: 0-5 years (4.1%), 6-10 (7.1%), 11-15 (13.6%), 16-21 (20.8%), 22-30
      (21.1%), and > 30 (33.3%). The disease predominantly affected males (70.1%) and
      agricultural workers (52.5%), followed by students (17.7%), and domestic workers
      (16.0%). Like the sand fly vector, the disease was distributed throughout the
      year, but the greatest concentration of cases was recorded in the dry season
      (58.5%), while sand flies presented bimodal peaks in the first two years and
      occurred more frequently in the rainy season in 1998. The disease continues to
      present the same characteristics as in the past, but there was a proportional
      increase in cases among children and females, suggesting transmission in the
      anthropic environment.

PMID- 15263985
TI  - [Health services waste management: a biosafety issue].
AB  - The subject of "health services waste" is controversial and widely discussed.
      Biosafety, the principles of which include safeguarding occupational health,
      community health, and environmental safety, is directly involved in the issue of
      medical waste management. There are controversies as to the risks posed by
      medical waste, as evidenced by diverging opinions among authors: some advocate
      severe approaches on the basis that medical waste is hazardous, while others
      contend that the potential for infection from medical waste is nonexistent. The
      Brazilian National Health Surveillance Agency (ANVISA) has published resolution
      RDC 33/2003 to standardize medical waste management nationwide. There is an
      evident need to implement biosafety procedures in this area, including heath care
      workers' training and provision of information to the general population.

PMID- 15263986
TI  - [Healthcare rights: an invitation for reflection].
AB  - This study focuses on changes and breaks in contemporary society relating to the
      right to healthcare as a universal value, in conformity with the guidelines
      provided by multilateral agencies and disseminated particularly since the 1990s.
      From the genesis of social rights and by tracing the interdependence between
      social and economic aspects of social citizenship in democratic capitalist
      countries, the study presents the two paradigms informing the approach to
      healthcare in the early 21st century: the full citizenship paradigm, according to
      which the right to healthcare is a universal value, and the paradigm of
      restricted social citizenship, according to which the right to healthcare is
      guided by the criterion of efficiency and economic rationalization. These
      propositions align with the health economy paradigm, which (i) defends focused
      resource allocation to attenuate poverty conditions, (ii) reduces the role of the
      state, (iii) recommends resource allocation to healthcare in association with
      social protection, and (iv) defines the market as the privileged regulator of
      healthcare actions.

PMID- 15263987
TI  - [Validation of a health survey questionnaire focusing on risk factors for
      coronary artery disease in a group of public employees in Juiz de Fora, Minas
      Gerais State, Brazil].
AB  - The validity of a health survey questionnaire used in a family health promotion
      program to identify individuals at risk of developing coronary artery disease
      (CAD) was studied in a random sample of 297 State public employees in Juiz de
      Fora, Minas Gerais State, Brazil. The sample was stratified by sex, and subjects
      were 40 years of age or older. Results obtained in interviews were compared to
      laboratory and clinical data. We assessed the questionnaire's sensitivity,
      specificity, and positive and negative predictive values in relation to questions
      about current or previous history of diabetes, hypertension, smoking, and high
      cholesterol. Among individuals with at least one altered clinical or laboratory
      test, 81% (total sensitivity) were identified by the referred risk inquiry when
      reporting at least one risk factor. Sheffield and New Zealand tables were used to
      determine the individuals with increased risk of developing CAD and to assess if
      they would also be identified by the health survey questionnaire. The sensitivity
      for identifying this subgroup was 100%.

PMID- 15263988
TI  - [Family planning and tubal ligation: analysis of the work of a team of health
      providers].
AB  - This article presents partial results from a study aimed at recognizing the work
      of members of a public health team who regularly perform tubal ligations.
      Empirical data were obtained through interviews and observation of routine
      activities by nine team members. The principal analytical categories were health
      work concepts. The team was basically characterized as hierarchical, but the
      specific decision on surgical sterilization tended to become more horizontal,
      with a tendency towards a multidisciplinary approach. This situation tends to
      involve the ethical dimension, with a shift from scientific and biomedical
      knowledge to the social sciences and humanities. On the other hand, and in a
      contradictory way, in the actual decision to perform surgical sterilization,
      technical criteria are supported by biomedical knowledge, and comprehensive
      knowledge is relegated to a secondary role.

PMID- 15263989
TI  - [Discovery-based teaching and learning strategies in health: problematization and
      problem-based learning].
AB  - Considering the changes in teaching in the health field and the demand for new
      ways of dealing with knowledge in higher learning, the article discusses two
      innovative methodological approaches: problem-based learning (PBL) and
      problematization. Describing the two methods' theoretical roots, the article
      attempts to identify their main foundations. As distinct proposals, both
      contribute to a review of the teaching and learning process: problematization,
      focused on knowledge construction in the context of the formation of a critical
      awareness; PBL, focused on cognitive aspects in the construction of concepts and
      appropriation of basic mechanisms in science. Both problematization and PBL lead
      to breaks with the traditional way of teaching and learning, stimulating
      participatory management by actors in the experience and reorganization of the
      relationship between theory and practice. The critique of each proposal's
      possibilities and limits using the analysis of their theoretical and
      methodological foundations leads us to conclude that pedagogical experiences
      based on PBL and/or problematization can represent an innovative trend in the
      context of health education, fostering breaks and more sweeping changes.

PMID- 15263990
TI  - [Pregnant women's perceptions of the Family Health Program concerning barriers to
      dental care in Pernambuco, Brazil].
AB  - This study focused on barriers to dental care for pregnant women registered with
      the Health Family Program in Cabo de Santo Agostinho, Pernambuco, Brazil. A
      qualitative approach using three focal groups was adopted. Each focal group
      included four to nine pregnant women. The information was analyzed by means of
      content analysis. The main individual barriers were folk beliefs that discouraged
      dental care during pregnancy, lack of perceived need, and fear of pain. In
      addition, the women reported difficulties in leaving home in the early hours of
      the morning to meet a dental appointment, highlighting an aspect of barriers to
      dental care which has not been identified in other studies. The article concludes
      by emphasizing the importance of health education for pregnant women,
      humanization of dental care, and continuing education for health professionals.

PMID- 15263991
TI  - [Health and work in the construction industry in an urban area of Brazil].
AB  - This community-based survey in the city of Salvador, capital of Bahia State,
      Brazil, describes the occupational and health profile of construction workers.
      All 1,947 male individuals between 10 and 65 years of age identified in a random
      cluster area single-stage sample were individually interviewed. Narrative data
      about work injuries were also analyzed. Construction workers were older, more
      frequently black, poorer, and had less schooling and a higher proportion of
      informal job contracts than those in other trades. The majority (55.8%) reported
      wanting a formal job in order to be eligible for paid retirement. Smoking
      (prevalence ratio = 1.37; 95% CI: 1.08-1.72) and nonfatal work injuries (relative
      risk = 1.72; 95% CI: 1.49-7.42) were more common among construction workers.
      Narrative data show lack of information and lack of access to personal protective
      equipment. Prevention programs and the formalization of job contracts are
      strongly recommended for construction workers.

PMID- 15263992
TI  - [Nutritional status and factors associated with stunting in children attending
      public daycare centers in the Municipality of Sao Paulo, Brazil].
AB  - This study reports the nutritional status of children attending daycare centers
      in the Municipality of Sao Paulo, Brazil. A representative sample of 827 children
      under 84 months of age was evaluated. Anthropometric measurements and information
      on socioeconomic characteristics and morbidity were collected. The most prevalent
      nutritional deficit was stunting (7.0%; 95%CI: 3.60-10.40). Univariate analysis
      showed a significant association between stunting and age (< 24 months), OR =
      2.10 (95%CI: 1.11-3.98); diarrhea one month prior to the data collection, OR =
      2.84 (95%CI: 1.42-5.66); mother's or caregiver's schooling (< 3 years), OR = 3.87
      (95%CI: 1.10-13.68); number of household members (> 7), OR = 3.02(95%CI: 1.46
      6.22); and number of siblings (> 2) OR = 4.81 (95%CI: 1.72-13.44). In the
      multivariate analysis, only diarrhea one month prior to the data collection, OR =
      2.54 (95%CI: 1.20-5.38) and > 2 siblings, OR = 7.40 (95%CI: 2.20-24.93), remained
      associated with stunting.

PMID- 15263993
TI  - [Female depression viewed from women's subjectivity].
AB  - The aim of the study was to explore the way in which depression in women is
      conceptualized, experienced, and given meaning from the perspective of the women
      themselves, based on a review of text material on the subject. The focus group
      technique was used to present the text, which deals with depression, its causes,
      and coping strategies. Twenty-seven women, divided into four groups, participated
      in the study. Analyses of the transcriptions of self-recordings led to the
      identification of four categories: the experience of depression, childhood
      experiences, the female social condition, and coping strategies. The majority
      mentioned having had bouts of depression in their lives, although they had not
      recognized them as such. They were aware of the role played by socialization of
      the female role and certain childhood events in the emergence of depression and
      used various strategies to cope with this. The women found similarities between
      the ways they perceived depression and the descriptions in the text, and shared
      their own experiences. Depression was reported as a central theme in their lives,
      and they were eager to talk about it.

PMID- 15263994
TI  - [Prevalence of dental caries in schoolchildren in the rural area of Itapetininga,
      Sao Paulo State, Brazil].
AB  - The present study is an attempt to characterize dental needs of the rural
      population in Itapetininga, Sao Paulo State, Brazil. One single dentist examined
      291 children ages 5 and 12 years in rural schools, adopting WHO criteria for oral
      health surveys. Parents reported their children's socioeconomic characteristics
      and habits. Non-primary data gathered by the Brazilian health authority supplied
      information regarding the schoolchildren in the urban area of the town. Caries
      indices ranked as follows: dmft = 2.63 (5-year-old children) and DMFT = 2.45 (12
      year-old children). The decayed component comprised 85.6% of the dmft and 34.2%
      of the DMFT, indicating limited utilization of dental treatment by children with
      decayed deciduous teeth. Caries prevalence was higher in rural schoolchildren
      than in their urban counterparts. Analysis of the results aims to improve
      planning of dental care.

PMID- 15263995
TI  - [Utilization of community mental health services in the city of Santos, Sao
      Paulo, Brazil].
AB  - To report on the clientele treated at community mental health services (CAPS) in
      the city of Santos, Sao Paulo, Brazil, a census was conducted of the patients
      examined at the services from June 1, 2001, to June 30, 2001. The patient's
      initial contact with the service was registered, and data were recorded on a
      standardized form, using the medical case history as a source of information.
      Among the 1,673 patients, average age was 46 years, 59.0% were female, 58.0%
      lived with their families, and mean duration of treatment was three years. Some
      38.0% were schizophrenic, schizotypical, or in acute delusional states, 31.0%
      presented mood disorders, and 17.0% were neurotic. Treatment modalities included
      out-patient psychiatric (81.0%), individual (23.0%), group (13.0%), and
      psychosocial rehabilitation (4.3%). In Santos, CAPS treat all categories of
      mental disorders (and frequently those considered the most severe cases) expected
      at this type of service. The treatment model is that of an out-patient
      psychiatric clinic.

PMID- 15263996
TI  - [Consenting to ambiguities: a documental analysis of informed consent forms used
      in assisted human reproduction clinics].
AB  - With the field of assisted human reproduction as a case study, this article
      presents the results of a study on informed consent forms, linking the
      understanding of the use of social languages - especially the language of risk -
      and its implications on the relationship between health professionals and
      clients. Informed by a social psychology perspective and aligned with the
      qualitative tradition in research, the study was oriented by a theoretical
      approach to discursive practice, whereby the language of risk is understood as a
      way of speaking of future control of risks. The analysis centered on the text of
      27 informed consent forms provided by eight Brazilian clinics. Besides
      understanding the linguistic specificities, the analysis attempted to answer the
      question, "What is being consented to?" The results showed the ambiguity of a
      document which presupposes the use of the metaphor of taking versus not taking
      risks. That is, the document may be used in a democratic, bureaucratic, or even
      authoritarian way, while the communication of risks and benefits subsidizes both
      the decision-making and the dilution of responsibility throughout the relational
      network.

PMID- 15263997
TI  - [Plato's philosophy and the bioethical debate on the end of life: intersections
      in public health].
AB  - This article discusses bioethical aspects of medical futility, focusing on some
      of its intersections in public health. Starting from a demarcation of finitude in
      the core of the philosophical and bioethical debate on the end of life, we
      confront the contemporary criticism regarding medical futility with the ideas of
      Plato (427-347 B.C.), a philosopher who proposed significant considerations on
      numerous features of the medicine of his time. We thus explore novel theoretic
      references to guide the disputes related to this essential problem, the
      implications of which are decisive to health and life.

PMID- 15263998
TI  - [Dental caries in Paulinia, Sao Paulo State, Brazil, and WHO goals for 2000 and
      2010].
AB  - An epidemiological survey was conducted in Paulinia, Sao Paulo State, Brazil, in
      2000, aimed at verifying the prevalence of principal oral health problems, using
      the DMFT index and WHO diagnostic criteria. The sample (1,151) was randomly
      selected. The dmft was 1.90 in 5-year-olds, with 54.2% caries-free. DMFT was 1.00
      in 12-year-olds, with 46.4% caries-free in the permanent dentition. Fluorosis
      prevalence in 7 to 12-year-olds was 30.5%, mostly the very mild form (22.9%).
      Prevalence of opacities and hypoplasias was 9.1%. In adults, the dental care
      index was 55.4% and an average of 21.30 teeth presented caries experience. In the
      elderly, DMFT was 29.50, consisting predominantly of extracted teeth (93.0%).

PMID- 15263999
TI  - Evaluation by blue native polyacrylamide electrophoresis colorimetric staining of
      the effects of physical exercise on the activities of mitochondrial complexes in
      rat muscle.
AB  - Blue native polyacrylamide electrophoresis (BN-PAGE) is a technique developed for
      the analysis of membrane complexes. Combined with histochemical staining, it
      permits the analysis and quantification of the activities of mitochondrial
      oxidative phosphorylation enzymes using whole muscle homogenates, without the
      need to isolate muscle mitochondria. Mitochondrial complex activities were
      measured by emerging gels in a solution containing all specific substrates for
      NADH dehydrogenase and cytochrome c oxidase enzymes (complexes I and IV,
      respectively) and the colored bands obtained were measured by optique
      densitometry. The objective of the present study was the application of BN-PAGE
      colorimetric staining for enzymatic characterization of mitochondrial complexes I
      and IV in rat muscles with different morphological and biochemical properties. We
      also investigated these activities at different times after acute exercise of rat
      soleus muscle. Although having fewer mitochondria than oxidative muscles, white
      gastrocnemius muscle presented a significantly higher activity (26.7 +/- 9.5) in
      terms of complex I/V ratio compared to the red gastrocnemius (3.8 +/- 0.65, P <
      0.05) and soleus (9.8 +/- 0.9, P < 0.001) muscles. Furthermore, the complex IV/V
      ratio of white gastrocnemius muscle was always significantly higher when compared
      to the other muscles. Ninety-five minutes of exhaustive physical exercise induced
      a decrease in complex I/V and complex IV/V ratios after all resting times (0, 3
      and 6 h) compared to control (P < 0.05), probably reflecting the oxidative damage
      due to increasing free radical production in mitochondria. These results
      demonstrate the possible and useful application of BN-PAGE-histochemical staining
      to physical exercise studies.

PMID- 15264000
TI  - Recombinant antigen-based immuno-slot blot method for serodiagnosis of syphilis.
AB  - Three recombinant antigens of Treponema pallidum Nichols strain were fused with
      GST, cloned and expressed in Escherichia coli, resulting in high levels of GST
      rTp47 and GST-rTp17 expression, and supplementation with arginine tRNA for the
      AGR codon was needed to obtain GST-rTp15 overexpression. Purified fusion protein
      yields were 1.9, 1.7 and 5.3 mg/l of cell culture for GST-rTp47, GST-rTp17 and
      GST-rTp15, respectively. The identities of the antigens obtained were confirmed
      by automated DNA sequencing using ABI Prism 310 and peptide mapping by Finningan
      LC/MS. These recombinant antigens were evaluated by immuno-slot blot techniques
      applied to 137 serum samples from patients with a clinical and laboratory
      diagnosis of syphilis (61 samples), from healthy blood donors (50 samples),
      individuals with sexually transmitted disease other than syphilis (3 samples),
      and from individuals with other spirochetal diseases such as Lyme disease (20
      samples) and leptospirosis (3 samples). The assay had sensitivity of 95.1% (95%
      CI, 86.1 to 98.7%) and a specificity of 94.7% (95% CI, 87.0 to 98.7%); a stronger
      reactivity was observed with fraction rTp17. The immunoreactivity results showed
      that fusion recombinant antigens based-immuno-slot blot techniques are suitable
      for use in diagnostic assays for syphilis.

PMID- 15264001
TI  - Elevated levels of erythrocyte-conjugated dienes indicate increased lipid
      peroxidation in schistosomiasis mansoni patients.
AB  - Schistosoma mansoni causes liver disease by inducing granulomatous inflammation.
      This favors formation of reactive oxygen species, including superoxide ions,
      hydrogen peroxide and hydroxyl radicals all of which may induce lipid
      peroxidation. We have evaluated lipid peroxidation in 18 patients with
      hepatosplenic schistosomiasis mansoni previously treated with oxamniquine
      followed by splenectomy, ligature of the left gastric vein and auto-implantation
      of spleen tissue, by measuring levels of erythrocyte-conjugated dienes and plasma
      malondialdehyde (MDA). Age-matched, healthy individuals (N = 18) formed the
      control group. Erythrocyte-conjugated dienes were extracted with
      dichloromethane/methanol and quantified by UV spectrophotometry, while plasma MDA
      was measured by reaction with thiobarbituric acid. Patient erythrocytes contained
      two times more conjugated dienes than control cells (584.5 +/- 67.8 vs 271.7 +/-
      20.1 micromol/l, P < 0.001), whereas the increase in plasma MDA concentration
      (about 10%) was not statistically significant. These elevated conjugated dienes
      in patients infected by S. mansoni suggest increased lipid peroxidation in cell
      membranes, although this was not evident when a common marker of oxidative
      stress, plasma MDA, was measured. Nevertheless, these two markers of lipid
      peroxidation, circulating MDA and erythrocyte-conjugated dienes, correlated
      significantly in both patient (r = 0.62; P < 0.01) and control (r = 0.57; P <
      0.05) groups. Our data show that patients with schistosomiasis have abnormal
      lipid peroxidation, with elevated erythrocyte-conjugated dienes implying
      dysfunctional cell membranes, and also imply that this may be attenuated by the
      redox capacity of antioxidant agents, which prevent accumulation of plasma MDA.

PMID- 15264002
TI  - Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine
      and hemin.
AB  - The binding of chlorpromazine (CPZ) and hemin to bovine serum albumin was studied
      by the fluorescence quenching technique. CPZ is a widely used anti-psychotic drug
      that interacts with blood components, influences bioavailability, and affects
      function of several biomolecules. Hemin is an important ferric residue of
      hemoglobin that binds within the hydrophobic region of albumin with high
      specificity. Quenching of the intrinsic fluorescence of bovine serum albumin
      (BSA) was observed by selectively exciting tryptophan residues at 290 nm.
      Emission spectra were recorded in the range from 300 to 450 nm for each quencher
      addition. Stern-Volmer graphs were plotted, and the quenching constant estimated
      for BSA solution titrated with hemin at 25 masculine C was 1.44 (+/- 0.05) x
      10(5) M(-1). Results showed that bovine albumin tryptophans are not equally
      accessible to CPZ, in agreement with the idea that polar or charged quenchers
      have more affinity for amino acid residues on the outer wall of the protein.
      Hemin added to albumin solution at a molar ratio of 1:1 quenched about 25% of
      their fluorescence. The quenching effect of CPZ on albumin-hemin solution was
      stronger than on pure BSA. This increase can be the result of combined
      conformational changes in the structure of albumin caused firstly by hemin and
      then by CPZ. Our results suggest that the primary binding site for hemin on
      bovine albumin may be located asymmetrically between the two tryptophans along
      the sequence formed by subdomains IB and IIA, closer to tryptophan residue 212.

PMID- 15264003
TI  - Neutralization of the edema-forming, defibrinating and coagulant effects of
      Bothrops asper venom by extracts of plants used by healers in Colombia.
AB  - We determined the neutralizing activity of 12 ethanolic extracts of plants
      against the edema-forming, defibrinating and coagulant effects of Bothrops asper
      venom in Swiss Webster mice. The material used consisted of the leaves and
      branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae),
      Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae);
      the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea
      (Bignoniaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and
      Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia
      (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii
      (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of
      varying amounts of each extract with either 1.0 microg venom for the edema
      forming effect or 2.0 microg venom for the defibrinating effect, the mixture was
      injected subcutaneously (sc) into the right foot pad or intravenously into the
      tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200
      microg/mouse) partially neutralized the edema-forming activity of venom in a dose
      dependent manner (58-76% inhibition), with B. orellana, S. orbicularis, G.
      panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten
      extracts (3.9-2000 microg/mouse) also showed 100% neutralizing ability against
      the defibrinating effect of venom, and nine prolonged the coagulation time
      induced by the venom. When the extracts were administered either before or after
      venom injection, the neutralization of the edema-forming effect was lower than
      40% for all extracts, and none of them neutralized the defibrinating effect of
      venom. When they were administered in situ (sc at the same site 5 min after venom
      injection), the neutralization of edema increased for six extracts, reaching
      levels up to 64% for C. limon.

PMID- 15264004
TI  - Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats.
AB  - The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination
      with gentamicin poses the additional risk of nephrotoxic renal failure.
      Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of
      renal vasodilator prostaglandins, while COX-2 participates predominantly in the
      inflammatory process. Both are inhibited by non-selective NSAID such as
      indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer
      renal side effects than non-selective inhibitors. The objective of the present
      study was to determine whether the combined use of rofecoxib and gentamicin can
      prevent the increased renal injury caused by gentamicin and indomethacin. Male
      Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip,
      N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N =
      7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin +
      indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine
      clearance and alpha-glutathione-S-transferase concentrations were used as markers
      of renal injury. Animals were anesthetized with ether and sacrificed for blood
      collection. The use of gentamicin plus indomethacin led to worsened renal
      function (0.199 +/- 0.019 ml/min), as opposed to the absence of a nephrotoxic
      effect of rofecoxib when gentamicin plus rofexicob was used (0.242 +/- 0.011
      ml/min). These results indicate that COX-2-selective inhibitors can be used as an
      alternative treatment to conventional NSAID, especially in situations in which
      risk factors for nephrotoxicity are present.

PMID- 15264005
TI  - Effects of melatonin on the ovarian response to pinealectomy or continuous light
      in female rats: similarity with polycystic ovary syndrome.
AB  - The current study was conducted to investigate the relationship between melatonin
      and chronic anovulation. Adult (3-4 months old) female Wistar rats were submitted
      to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N =
      10); group II: pinealectomized ovariectomized placebo-treated (N = 12); group
      III: pinealectomized light-treated placebo-treated (N = 10) or maintained under
      continuous light; group IV: maintained under continuous light, ovariectomized
      melatonin-treated (N = 22); group V: maintained under continuous light,
      ovariectomized placebo-treated (N = 10); group VI: maintained under continuous
      light placebo-treated (N = 10). In order to assess ovarian modifications,
      unilateral ovariectomy was performed during the fourth month in groups I, II, IV,
      V and the other ovary was removed after 8 months. Ovariectomy was performed in
      groups III and VI only after eight months. Melatonin (200 micro g/100 g body
      weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily
      during the last 4 months into groups I and IV. The other groups were treated with
      placebo (NaCl). The ovarian cysts were analyzed and their area, perimeter and
      maximum diameter, as well as the thickness of the ovarian capsule were measured.
      Daily colpocytological smears were performed throughout the study. Persistent
      estrous condition and ovarian cysts were observed in all groups. In
      pinealectomized rats the ovarian and vaginal alterations disappeared at the end
      of the study and in rats maintained under continuous light the vaginal and
      ovarian polycystic aspect was reversed only in those treated with melatonin. We
      conclude that melatonin may act on the ovarian response reverting chronic
      anovulation induced by pinealectomy or continuous light.

PMID- 15264006
TI  - Colocalization of coilin and nucleolar proteins in Cajal body-like structures of
      micronucleated PtK2 cells.
AB  - Cajal bodies (CB) are ubiquitous nuclear structures involved in the biogenesis of
      small nuclear ribonucleoproteins and show narrow association with the nucleolus.
      To identify possible relationships between CB and the nucleolus, the localization
      of coilin, a marker of CB, and of a set of nucleolar proteins was investigated in
      cultured PtK2 cells undergoing micronucleation. Nocodazol-induced micronucleated
      cells were examined by double indirect immunofluorescence with antibodies against
      coilin, fibrillarin, NOR-90/hUBF, RNA polymerase I, PM/Scl, and To/Th. Cells were
      imaged on a BioRad 1024-UV confocal system attached to a Zeiss Axiovert 100
      microscope. Since PtK2 cells possess only one nucleolus organizer region,
      micronucleated cells presented only one or two micronuclei containing nucleolus.
      By confocal microscopy we showed that in most micronuclei lacking a typical
      nucleolus a variable number of round structures were stained by antibodies
      against fibrillarin, NOR-90/hUBF protein, and coilin. These bodies were regarded
      as CB-like structures and were not stained by anti-PM/Scl and anti-To/Th
      antibodies. Anti-RNA polymerase I antibodies also reacted with CB-like structures
      in some micronuclei lacking nucleolus. The demonstration that a set of proteins
      involved in RNA/RNP biogenesis, namely coilin, fibrillarin, NOR-90/hUBF, and RNA
      polymerase I gather in CB-like structures present in nucleoli-devoid micronuclei
      may contribute to shed some light into the understanding of CB function.

PMID- 15264007
TI  - Effect of the Escherichia coli EMO strain on experimental infection by Salmonella
      enterica serovar Typhimurium in gnotobiotic mice.
AB  - An experimental infection with Salmonella enterica subsp. enterica serovar
      Typhimurium was evaluated in gnotobiotic mice previously exposed to a plasmid
      free non-pathogenic Escherichia coli (EMO strain). Mice were exposed to EMO
      (experimental) or not (control) 10 days before challenge with Salmonella
      Typhimurium (10(2) colony forming units (CFU)/mouse). Survival after challenge
      was higher (P < 0.05) in the experimental group (16%) than in the control animals
      (0%). Histopathological examination of the colon and ileum mucosa of the
      experimental group showed less extensive lesions such as edema, cell inflammatory
      infiltration and hyperemia. The epithelial cells of the mucosal surface and the
      production of the mucous layer were also better preserved in the experimental
      group. The population levels of Salmonella Typhimurium in the feces were
      initially 10-fold lower (P < 0.05) in the experimental groups. However, 3 days
      after challenge both experimental and control groups showed similar population
      levels ranging from 10(8) to 10(9) CFU/g of feces. The intestinal contents of
      total and anti-Salmonella Typhimurium sIgA were higher in the experimental groups
      10 days after inoculation of E. coli EMO strain. Translocation of Salmonella
      Typhimurium to the spleen was 10-fold lower (P < 0.05) in the experimental group
      only on day 3 after infection. This was not related to an increase in the
      bacterial blood clearance of the animals, as shown by experimental venous
      challenge with E. coli B41. In conclusion, treatment of mice with E. coli EMO
      strain promoted a relative protection against experimental infection with
      Salmonella Typhimurium. This protection was not due to the reduction of the
      population of pathogens in the intestine but was probably related to stimulation
      of the immune response.

PMID- 15264008
TI  - An experimental model of mycobacterial infection under corneal flaps.
AB  - In order to develop a new experimental animal model of infection with
      Mycobacterium chelonae in keratomileusis, we conducted a double-blind prospective
      study on 24 adult male New Zealand rabbits. One eye of each rabbit was submitted
      to automatic lamellar keratotomy with the automatic corneal shaper under general
      anesthesia. Eyes were immunosuppressed by a single local injection of methyl
      prednisolone. Twelve animals were inoculated into the keratomileusis interface
      with 1 microl of 10(6) heat-inactivated bacteria (heat-inactivated inoculum
      controls) and 12 with 1 microl of 10(6) live bacteria. Trimethoprim drops (0.1%,
      w/v) were used as prophylaxis for the surgical procedure every 4 h (50 microl,
      qid). Animals were examined by 2 observers under a slit lamp on the 1st, 3rd,
      5th, 7th, 11th, 16th, and 23rd postoperative days. Slit lamp photographs were
      taken to document clinical signs. Animals were sacrificed when corneal disease
      was detected and corneal samples were taken for microbiological analysis. Eleven
      of 12 experimental rabbits developed corneal disease, and M. chelonae could be
      isolated from nine rabbits. Eleven of the 12 controls receiving a heat
      inactivated inoculum did not develop corneal disease. M. chelonae was not
      isolated from any of the control rabbits receiving a heat-inactivated inoculum,
      or from the healthy cornea of control rabbits. Corneal infection by M. chelonae
      was successfully induced in rabbits submitted to keratomileusis. To our
      knowledge, this is the first animal model of M. chelonae infection following
      corneal flaps for refractive surgery to be described in the literature and can be
      used for the analysis of therapeutic responses.

PMID- 15264009
TI  - In situ enzyme immunoassay for titration of a Brazilian hepatitis A virus strain
      (HAF-203).
AB  - Hepatitis A virus (HAV) replicates relatively slowly in cell culture without a
      cytopathic effect, a fact that limits the use of tissue culture assays. The
      radioimmunofocus assay is the standard method for HAV titration, although it is
      labor intensive and requires the use of radioisotopes. A simple, rapid and
      objective infectivity assay based on an in situ enzyme immunoassay (EIA) is
      described here for a Brazilian cell culture-adapted HAV strain (HAF-203). The
      assay uses a peroxidase-labeled polyclonal antibody to fixed monolayers as an
      indicator of infection. EIA may be completed within 7 days using serial 5-fold
      dilutions of the virus, yielding a titer of 5.024 log 50% tissue culture
      infective dose (TCID50)/ml for HAF-203. This technique had a detection limit of
      1.1 log TCID50/ml and the specificity was demonstrated by detecting no reaction
      on the columns of uninfected wells. The reproducibility (with intra- and inter
      assay coefficients of variation ranging from 1.9 to 3.8% and from 3.5 to 9.9%,
      respectively) and quantitation of the assay were demonstrated by close agreement
      in virus infectivity titers among different assays of the same amount of virus
      and between assays of different amounts of virus. Furthermore, this assay does
      not require the use of radiolabeled antibodies. We describe here an efficient EIA
      that is highly reproducible and that could be used to monitor HAV growth in cell
      culture and to determine the quantity of HAV antigen needed for diagnostic
      assays. This is the first report of the infectious titer of the Brazilian cell
      culture-adapted HAV strain (HAF-203).

PMID- 15264010
TI  - Tomato and garlic by gavage modulate 7,12-dimethylbenz[a]anthracene-induced
      genotoxicity and oxidative stress in mice.
AB  - Chemoprotection by dietary agents is a promising strategy for cancer prevention.
      The aim of the present study was to evaluate the combined effect of tomato and
      garlic against 7,12-dimethylbenz-[a]anthracene (DMBA)-induced genetic damage and
      oxidative stress in 12-14-week-old male Swiss albino mice. The animals were
      randomized into experimental and control groups and divided into eight groups of
      five animals each. Group 1 animals were injected intraperitoneally with 35 mg/kg
      body weight DMBA suspended in peanut oil as a single dose. Groups 2-4 animals
      received tomato (500 mg/kg body weight), garlic (125 mg/kg body weight) and a
      combination of tomato and garlic for 5 days by gavage, respectively, followed by
      DMBA 1.5 h after the final feeding. The doses of tomato and garlic correspond to
      the average human daily consumption. Animals in groups 5, 6 and 7 received tomato
      alone, garlic alone and tomato + garlic combination, respectively, for 5 days.
      Group 8 animals received the same volume of water and served as control. The
      incidence of bone marrow micronuclei and the extent of lipid peroxidation and the
      concentrations of antioxidants glutathione, glutathione peroxidase and
      glutathione-S-transferase were measured in the liver, 48 h after DMBA exposure.
      Increased frequency of micronuclei and enhanced lipid peroxidation accompanied by
      compromised antioxidant defenses were observed in DMBA-treated animals. Although
      pretreatment with tomato or garlic significantly reduced the frequency of DMBA
      induced bone marrow micronuclei, the combination of tomato and garlic exhibited
      more profound effect in inhibiting DMBA-induced genotoxicity and oxidative
      stress. We suggest that a broad spectrum of antimutagenic and anticlastogenic
      effects can be achieved through an effective combination of functional foods such
      as tomato and garlic.

PMID- 15264011
TI  - The interaction of housing condition and acute immobilization stress on the
      elevated plus-maze behaviors of protein-malnourished rats.
AB  - Protein malnutrition induces structural, neurochemical and functional alterations
      in the central nervous system, leading to behavioral alterations. In the present
      study, we used the elevated plus-maze (EPM) as a measure of anxiety to evaluate
      the interaction between acute immobilization and housing conditions on the
      behavior of malnourished rats. Pups (6 males and 2 females) were fed by Wistar
      lactating dams receiving a 6% (undernourished) or 16% (well-nourished) protein
      diet. After weaning, the animals continued to receive the same diets ad libitum
      until 49 days of age when they started to receive a regular lab chow diet. From
      weaning to the end of the tests on day 70, the animals were housed under two
      different conditions, i.e., individual or in groups of three. On the 69th day,
      half of the animals were submitted to immobilization for 2 h, while the other
      half were undisturbed, and both groups were tested 24 h later for 5 min in the
      EPM. Independent of other factors, protein malnutrition increased, while
      immobilization and social isolation per se decreased, EPM exploration. Analysis
      of the interaction of diet vs immobilization vs housing conditions showed that
      the increased EPM exploration presented by the malnourished group was reversed by
      acute immobilization in animals reared in groups but not in animals reared
      individually. The interaction between immobilization and housing conditions
      suggests that living for a long time in social isolation is sufficiently
      stressful to reduce the responses to another anxiogenic procedure
      (immobilization), while living in groups prompts the animals to react to acute
      stress. Thus, it is suggested that housing condition can modulate the effects of
      an anxiogenic procedure on behavioral responses of malnourished rats in the EPM.

PMID- 15264012
TI  - Monoamines in the pedal plexus of the land snail Megalobulimus oblongus
      (Gastropoda, Pulmonata).
AB  - In molluscs, the number of peripheral neurons far exceeds those found in the
      central nervous system. Although previous studies on the morphology of the
      peripheral nervous system exist, details of its organization remain unknown.
      Moreover, the foot of the terrestrial species has been studied less than that of
      the aquatic species. As this knowledge is essential for our experimental model,
      the pulmonate gastropod Megalobulimus oblongus, the aim of the present study was
      to investigate monoamines in the pedal plexus of this snail using two procedures:
      glyoxylic acid histofluorescence to identify monoaminergic structures, and the
      unlabeled antibody peroxidase anti-peroxidase method using antiserum to detect
      the serotonergic component of the plexus. Adult land snails weighing 48-80 g,
      obtained from the counties of Barra do Ribeiro and Charqueadas (RS, Brazil), were
      utilized. Monoaminergic fibers were detected throughout the pedal musculature.
      Blue fluorescence (catecholamines, probably dopamine) was observed in nerve
      branches, pedal and subepithelial plexuses, and in the pedal muscle cells. Yellow
      fluorescence (serotonin) was only observed in thick nerves and in muscle cells.
      However, when immunohistochemical methods were used, serotonergic fibers were
      detected in the pedal nerve branches, the pedal and subepithelial plexuses, the
      basal and lateral zones of the ventral integument epithelial cells, in the pedal
      ganglion neurons and beneath the ventral epithelium. These findings suggest
      catecholaminergic and serotonergic involvement in locomotion and modulation of
      both the pedal ganglion interneurons and sensory information. Knowledge of
      monoaminergic distribution in this snail s foot is important for understanding
      the pharmacological control of reflexive responses and locomotive behavior.

PMID- 15264013
TI  - Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by
      dopamine treatment of neuroblastoma SK-N-SH cells.
AB  - Increased dopamine catabolism may be associated with oxidative stress and
      neuronal cell death in Parkinson's disease. The present study was carried out to
      examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1
      and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of
      selegiline and antioxidants on this expression. Cells were kept with close
      control of pH and were incubated with varying concentrations of dopamine (0.1-100
      microM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse
      transcription-polymerase chain reaction amplification. The mRNA expression of HO
      1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA
      increased after dopamine treatment, in a dose-dependent manner, in all cell lines
      studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2
      protein expression was analyzed by Western blotting. HO-1 protein was
      undetectable in untreated SK-N-SH cells and increased after treatment with
      dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells
      and the levels did not change as a result of treatment. Alpha-tocopherol (10-100
      microM) and ascorbic acid (100 microM) did not attenuate the effects of dopamine.
      Selegiline (10 microM) produced significant increase (P < 0.01) in the induction
      of HO-1 by dopamine (more than six times the control values). The increased
      expression of HO-1 following dopamine treatment indicates that dopamine produces
      oxidative stress in this cell line.

PMID- 15264014
TI  - Experimental context modulates warning signal effects.
AB  - Previous studies have shown that saccadic eye responses but not manual responses
      were sensitive to the kind of warning signal used, with visual onsets producing
      longer saccadic latencies compared to visual offsets. The aim of the present
      study was to determine the effects of distinct warning signals on manual
      latencies and to test the premise that the onset interference, in fact, does not
      occur for manual responses. A second objective was to determine if the magnitude
      of the warning effects could be modulated by contextual procedures. Three
      experimental conditions based on the kind of warning signal used (visual onset,
      visual offset and auditory warning) were run in two different contexts (blocked
      and non-blocked). Eighteen participants were asked to respond to the imperative
      stimulus that would occur some milliseconds (0, 250, 500 or 750 ms) after the
      warning signal. The experiment consisted in three experimental sessions of 240
      trials, where all the variables were counterbalanced. The data showed that visual
      onsets produced longer manual latencies than visual offsets in the non-blocked
      context (275 vs 261 ms; P < 0.001). This interference was obtained, however, only
      for short intervals between the warning and the stimulus, and was abolished when
      the blocked context was used (256 vs 255 ms; P = 0.789). These results are
      discussed in terms of bottom-up and top-down interactions, mainly those related
      to the role of attentional processing in cancelling out competitive interactions
      and suppressive influences of a distractor on the relevant stimulus.

PMID- 15264015
TI  - The alga Bryothamnion seaforthii contains carbohydrates with antinociceptive
      activity.
AB  - Bryothamnion seaforthii, a red alga common to the Northeastern coast of Brazil,
      was used to prepare the protein fraction F0/60 by ammonium sulfate precipitation.
      The chromatography of F0/60 on DEAE-Sephadel column resulted in two lectin
      fractions, PI and PII, which have antinociceptive properties in rodents. We
      determined the antinociceptive activity of the PII fraction and of a carbohydrate
      containing fraction (CF) in mice. The CF was prepared from the dried algae, after
      digestion with 100 mM sodium acetate, pH 6.0, containing 5 mM cysteine, EDTA and
      0.4% papain, at 60 masculine C. A 10% cetylpyridinium chloride was added to the
      filtrate, and the precipitate was dissolved with 2 M NaCl:ethanol (100:15, v/v)
      followed by the carbohydrate precipitation with ethanol. The final precipitate,
      in acetone, was dried at 25 masculine C. The PII fraction markedly inhibited
      acetic acid-induced abdominal writhing after ip administration (control: 27.1 +/-
      2.20; PII 0.1 mg/kg: 5.5 +/- 1.85; 1 mg/kg: 1.6 +/- 0.72 writhes/20 min) and
      after oral administration (control: 32.0 +/- 3.32; PII 0.1 mg/kg: 13.1 +/- 2.50;
      1 mg/kg: 9.4 +/- 3.96 writhes/20 min). PII was also effective against both phases
      of pain induced by 1% formalin (control, ip: 48.2 +/- 2.40 and 27.7 +/- 2.56 s;
      PII: 1 mg/kg, ip: 34.3 +/- 5.13 and 5.6 +/- 2.14 s; control, po: 44.5 +/- 3.52
      and 25.6 +/- 2.39 s; PII 5 mg/kg, po: 26.5 +/- 4.67 and 15.3 +/- 3.54 s for the
      1st and 2nd phases, respectively) and in the hot-plate test. The CF (ip) also
      displayed significant antinociceptive properties in all tests but at higher doses
      (1 and 5 mg/kg, ip and po). Thus, CF at the dose of 5 mg/kg significantly
      inhibited writhes (ip: 7.1 +/- 2.47 and po: 14.5 +/- 2.40 writhes/20 min) as well
      as the 1st (po: 19.6 +/- 1.74 s) and 2nd (po: 7.1 +/- 2.24 s) phases of the
      formalin test compared to controls ip and po. The antinociceptive effects of both
      the PII and CF in the formalin and hot-plate tests were prevented at least
      partially by pretreatment with the opioid receptor antagonist naloxone (2 mg/kg,
      sc). Moreover, both fractions retained antinociceptive activity in the acetic
      acid-induced writhing test following heating, a procedure which abolished the
      hemagglutinating activity of the fraction, presumably due to lectins also
      present. Finally, both fractions also prolonged the barbiturate-induced sleeping
      time. These results indicate that carbohydrate molecules present in the PII
      (26.8% carbohydrate) and CF (21% of the alga dried weight) obtained from B.
      seaforthii display pronounced antinociceptive activity which is resistant to heat
      denaturation and is mediated by an opioid mechanism, as indicated by naloxone
      inhibition.

PMID- 15264016
TI  - Spectral analysis of the electromyograph of the erector spinae muscle before and
      after a dynamic manual load-lifting test.
AB  - The aim of the present study was to assess the spectral behavior of the erector
      spinae muscle during isometric contractions performed before and after a dynamic
      manual load-lifting test carried out by the trunk in order to determine the
      capacity of muscle to perform this task. Nine healthy female students
      participated in the experiment. Their average age, height, and body mass (+/- SD)
      were 20 +/- 1 years, 1.6 +/- 0.03 m, and 53 +/- 4 kg, respectively. The
      development of muscle fatigue was assessed by spectral analysis (median
      frequency) and root mean square with time. The test consisted of repeated bending
      movements from the trunk, starting from a 45 masculine angle of flexion, with the
      application of approximately 15, 25 and 50% of maximum individual load, to the
      stand up position. The protocol used proved to be more reliable with loads
      exceeding 50% of the maximum for the identification of muscle fatigue by
      electromyography as a function of time. Most of the volunteers showed an increase
      in root mean square versus time on both the right (N = 7) and the left (N = 6)
      side, indicating a tendency to become fatigued. With respect to the changes in
      median frequency of the electromyographic signal, the loads used in this study
      had no significant effect on either the right or the left side of the erector
      spinae muscle at this frequency, suggesting that a higher amount and percentage
      of loads would produce more substantial results in the study of isotonic
      contractions.

PMID- 15264017
TI  - Cholesterol induces fetal rat enterocyte death in culture.
AB  - The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line
      originated from normal rat small intestine) was examined. Both cells were
      cultured in the presence of 20 to 80 microM cholesterol for up to 72 h. Apoptosis
      was determined by flow cytometric analysis and fluorescence microscopy. The
      expression of HMG-CoA reductase and peroxisome proliferator-activated receptor
      gamma (PPARgamma) was measured by RT-PCR. The addition of 20 microM cholesterol
      reduced enterocyte proliferation as early as 6 h of culture. Reduction of
      enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the
      presence and absence of 10% fetal calf serum, respectively, with the effect
      lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the
      proportion of cells with fragmented DNA by 9.7% at 40 microM and by 20.8% at 80
      microM. When the culture period was extended to 48 h, the effect of cholesterol
      was still more pronounced, with the percent of cells with fragmented DNA reaching
      53.5% for 40 microM and 84.3% for 80 microM. Chromatin condensation of IEC-6
      cells was observed after treatment with cholesterol even at 20 microM.
      Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent
      increase in PPARgamma expression in fetal rat enterocytes was observed. The
      expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and
      absence of fetal calf serum, respectively, with cholesterol at 80 mM. The
      apoptotic effect of cholesterol on enterocytes was possibly due to an increase in
      PPARgamma expression.

PMID- 15264018
TI  - Abnormal subcellular distribution of GLUT4 protein in obese and insulin-treated
      diabetic female dogs.
AB  - The GLUT4 transporter plays a key role in insulin-induced glucose uptake, which
      is impaired in insulin resistance. The objective of the present study was to
      investigate the tissue content and the subcellular distribution of GLUT4 protein
      in 4- to 12-year-old control, obese and insulin-treated diabetic mongrel female
      dogs (4 animals per group). The parametrial white adipose tissue was sampled and
      processed to obtain both plasma membrane and microsome subcellular fractions for
      GLUT4 analysis by Western blotting. There was no significant difference in
      glycemia and insulinemia between control and obese animals. Diabetic dogs showed
      hyperglycemia (369.9 +/- 89.9 mg/dl). Compared to control, the plasma membrane
      GLUT4, reported per g tissue, was reduced by 55% (P < 0.01) in obese dogs, and
      increased by 30% (P < 0.05) in diabetic dogs, and the microsomal GLUT4 was
      increased by approximately 45% (P < 0.001) in both obese and diabetic animals.
      Considering the sum of GLUT4 measured in plasma membrane and microsome as total
      cellular GLUT4, percent GLUT4 present in plasma membrane was reduced by
      approximately 65% (P < 0.001) in obese compared to control and diabetic animals.
      Since insulin stimulates GLUT4 translocation to the plasma membrane, percent
      GLUT4 in plasma membrane was divided by the insulinemia at the time of tissue
      removal and was found to be reduced by 75% (P < 0.01) in obese compared to
      control dogs. We conclude that the insulin-stimulated translocation of GLUT4 to
      the cell surface is reduced in obese female dogs. This probably contributes to
      insulin resistance, which plays an important role in glucose homeostasis in dogs.

PMID- 15264019
TI  - Biochemical characterization of the GM2 gangliosidosis B1 variant.
AB  - The deficiency of the A isoenzyme of beta-hexosaminidase (Hex) produced by
      different mutations of the gene that codes for the alpha subunit (Tay-Sachs
      disease) has two variants with enzymological differences: the B variant consists
      of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A
      isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with
      negative charge. In contrast to the early childhood form of the B variant, the B1
      variant appears at a later clinical stage (3 to 7 years of age) with
      neurodegenerative symptoms leading to the death of the patient in the second
      decade of life. The most frequent mutation responsible for the GM2 gangliosidosis
      B1 variant is R178H, which has a widespread geographic and ethnic distribution.
      The highest incidence has been described in Portugal, which has been suggested as
      the point of origin of this mutation. Biochemical characterization of this
      lysosomal disease is carried out using negatively charged synthetic alpha subunit
      specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are
      not applicable. However, the determination of the apparent activation energy of
      Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl
      beta-D-glucosaminide, may offer a valid alternative. The presence of an alpha
      subunit in the alphabeta heterodimer Hex A means that its activation energy (41.8
      kJ/mol) is significantly lower than that of the betabeta homodimer Hex B (75.1
      kJ/mol); however, as mutation inactivates the alpha subunit, the Hex A of the B1
      variant presents an activation energy that is similar to that of the Hex B
      isoenzyme.

PMID- 15264020
TI  - A calcineurin inhibitory protein overexpressed in Down's syndrome interacts with
      the product of a ubiquitously expressed transcript.
AB  - The Down's syndrome candidate region 1 (DSCR1) protein, encoded by a gene located
      in the human chromosome 21, interacts with calcineurin and is overexpressed in
      Down's syndrome patients. As an approach to clarifying a putative function for
      this protein, in the present study we used the yeast two-hybrid system to
      identify DSCR1 partners. The two-hybrid system is a method that allows the
      identification of protein-protein interactions through reconstitution of the
      activity of the yeast GAL 4 transcriptional activator. The gene DSCR1 fused to
      the GAL 4 binding domain (BD) was used to screen a human fetal brain cDNA library
      cloned in fusion with the GAL 4 activation domain (AD). Three positive clones
      were found and sequence analysis revealed that all the plasmids coded for the
      ubiquitously expressed transcript (UXT). UXT, which is encoded in human Xp11, is
      a 157-amino acid protein present in both cytosol and nucleus of the cells. This
      positive interaction of DSCR1 and UXT was confirmed in vivo by mating the yeast
      strain AH109 (MATa) expressing AD-UXT with the strain Y187 (MATalpha) expressing
      BD-DSCR1, and in vitro by co-immunoprecipitation experiments. These results may
      help elucidate a new function for DSCR1 and its participation in Down's syndrome
      pathogenesis.

PMID- 15264021
TI  - Different stress modalities result in distinct steroid hormone responses by male
      rats.
AB  - Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive
      function, the purpose of the present study was to examine the influence of PSD
      and other stressors (restraint, electrical footshock, cold and forced swimming, N
      = 10 per group) on steroid hormones in adult Wistar male rats. Rats were
      submitted to chronic stress for four days. The stressors (footshock, cold and
      forced swimming) were applied twice a day, for periods of 1 h at 9:00 and 16:00
      h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas
      PSD was continuous. Hormone determination was measured by chemiluminescent enzyme
      immunoassay (testosterone), competitive immunoassay (progesterone) and by
      radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that
      PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower
      testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4
      ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5
      ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1
      ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and
      estradiol levels were reduced in the PSD, footshock and restraint groups compared
      to the control, swimming and cold groups. A significant increase in
      corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock
      (169.6 ng/ml) groups. These changes may be thought to be the full steroidal
      response to stress of significant intensity. Thus, the data suggest that
      different stress modalities result in distinct steroid hormone responses, with
      PSD and footshock being the most similar.

PMID- 15264022
TI  - The Shiga toxin 2 B subunit inhibits net fluid absorption in human colon and
      elicits fluid accumulation in rat colon loops.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the large intestine
      causing a spectrum of disorders, including watery diarrhea, bloody diarrhea
      (hemorrhagic colitis), and hemolytic-uremic syndrome. It is estimated that
      hemolytic-uremic syndrome is the most common cause of acute renal failure in
      infants in Argentina. Stx is a multimeric toxin composed of one A subunit and
      five B subunits. In this study we demonstrate that the Stx2 B subunit inhibits
      the water absorption (Jw) across the human and rat colonic mucosa without
      altering the electrical parameters measured as transepithelial potential
      difference and short circuit current. The time-course Jw inhibition by 400 ng/ml
      purified Stx2 B subunit was similar to that obtained using 12 ng/ml Stx2
      holotoxin suggesting that both, A and B subunits of Stx2 contributed to inhibit
      the Jw. Moreover, non-hemorrhagic fluid accumulation was observed in rat colon
      loops after 16 h of treatment with 3 and 30 ng/ml Stx2 B subunit. These changes
      indicate that Stx2 B subunit induces fluid accumulation independently of A
      subunit activity by altering the usual balance of intestinal absorption and
      secretion toward net secretion. In conclusion, our results suggest that the Stx2
      B subunit, which is non-toxic for Vero cells, may contribute to the watery
      diarrhea observed in STEC infection. Further studies will be necessary to
      determine whether the toxicity of Stx2 B subunit may have pathogenic consequences
      when it is used as a component in an acellular STEC vaccine or as a vector in
      cancer vaccines.

PMID- 15264023
TI  - A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice.
AB  - Food allergy is most frequently the result of IgE-mediated hypersensitivity
      reactions. Here, we describe a chronic model in which some of the intestinal and
      systemic consequences of continuous egg white solution ingestion by ovalbumin
      sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were
      investigated. There was a 20% loss of body weight that began one week after
      antigen exposure and persisted throughout the experiment (3 weeks). The
      sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE,
      which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE,
      compared to sensitization values). Intestinal changes were determined by jejunum
      edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil
      infiltration with a peak at 48 h. By day 21 of continuous antigen exposure,
      histological findings were mild, with mast cell hyperplasia (100%) and increased
      mucus production (483%). Altogether, our data clearly demonstrate that, although
      immune stimulation was persistently occurring in response to continuous oral
      antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa,
      preventing overt pathology. The experimental model described here reproduces the
      clinical and pathological changes of mild chronic food allergy and may be useful
      for mechanistic studies of this common clinical condition.

PMID- 15264024
TI  - IgA response in serum and gut secretion in sensitized mice fed with the dust mite
      Dermatophagoides pteronyssinus extract.
AB  - Induced oral tolerance to mucosal-exposed antigens in immunized animals is of
      particular interest for the development of immunotherapeutic approaches to human
      allergic diseases. This is a unique feature of mucosal surfaces which represent
      the main contact interface with the external environment. However, the influence
      of oral tolerance on specific and natural polyreactive IgA antibodies, the major
      defense mechanism of the mucosa, is unknown. We have shown that oral
      administration of an extract of the dust mite Dermatophagoides pteronyssinus (Dp)
      to primed mice caused down-regulation of IgE responses and an increase in tumor
      growth factor-beta secretion. In the present study, we observed that primed
      inbred female A/Sn mice (8 to 10 weeks old) fed by gavage a total weight of 1.0
      mg Dp extract on the 6th, 7th and 8th days post-immunization presented normal
      secretion of IL-4 and IL-10 in gut-associated lymphoid tissue and a decreased
      production of interferon gamma induced by Dp in the draining lymph nodes (13,340
      +/- 3,519 vs 29,280 +/- 2,971 pg/ml). Mice fed the Dp extract also showed higher
      levels of serum anti-Dp IgA antibodies and an increase of IgA-secreting cells in
      mesenteric lymph nodes (N = 10), reflecting an increase in total fecal IgA
      antibodies (N = 10). The levels of secretory anti-Dp IgA antibodies increased
      after re-immunization regardless of Dp extract feeding. Oral tolerance did not
      interfere with serum or secretory IgA antibody reactivity related to self and non
      self antigens. These results suggest that induction of oral tolerance to a Dp
      extract in sensitized mice triggered different regulatory mechanisms which
      inhibited the IgE response and stimulated systemic and secretory IgA responses,
      preserving the natural polyreactive IgA antibody production.

PMID- 15264025
TI  - Abnormalities of hippocampal signal intensity in patients with familial mesial
      temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is associated with hippocampal atrophy and
      hippocampal signal abnormalities. In our series of familial MTLE (FMTLE), we
      found a high proportion of hippocampal abnormalities. To quantify signal
      abnormalities in patients with FMTLE we studied 152 individuals (46 of them
      asymptomatic) with FMTLE. We used NIH-Image for volumetry and signal
      quantification in coronal T1 inversion recovery and T2 for all cross-sections of
      the hippocampus. Values diverging by 2 or more SD from the control mean were
      considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all
      individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1
      hippocampal signal changes were found in 34% of all individuals: 42.5% of
      affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal
      head (first three slices) revealed T2 abnormalities in 73% of all individuals
      (74% of affected subjects and 72% of asymptomatic subjects) and T1 abnormalities
      in 59% (67% of affected subjects and 41% of asymptomatic subjects). Affected
      individuals had smaller volumes than controls (P < 0.0001). There was no
      difference in hippocampal volumes between asymptomatic subjects and controls,
      although 39% of asymptomatic patients had hippocampal atrophy. Patients with an
      abnormal hippocampal signal (133 individuals) had smaller ipsilateral volume, but
      no linear correlation could be determined. Hippocampal signal abnormalities in
      FMTLE were more frequently found in the hippocampal head in both affected and
      asymptomatic family members, including those with normal volumes. These results
      indicate that subtle abnormalities leading to an abnormal hippocampal signal in
      FMTLE are not necessarily related to seizures and may be determined by genetic
      factors.

PMID- 15264026
TI  - Social condition affects hormone secretion and exploratory behavior in rats.
AB  - Studies of behavior, endocrinology and physiology have described experiments in
      which animals housed in groups or in isolation were normally tested individually.
      The isolation of the animal from its group for testing is perhaps the most common
      situation used today in experimental procedures, i.e., there is no consideration
      of the acute stress which occurs when the animal is submitted to a situation
      different from that it is normally accustomed to, i.e., group living. In the
      present study, we used 90 male 120-day-old rats (Rattus norvegicus) divided into
      5 groups of 18 animals, which were housed 3 per cage, in a total of 6 cages. The
      animals were tested individually or with their groups for exploratory behavior.
      Hormones were determined by radioimmunoassay using specific kits. The results
      showed statistically significant differences between testing conditions in terms
      of behavior and of adrenocorticotrophic hormone (ACTH: from 116.8 +/- 15.27 to
      88.77 +/- 18.74 when in group and to 159.6 +/- 11.53 pg/ml when isolated),
      corticosterone (from 561.01 +/- 77.04 to 1036.47 +/- 79.81 when in group and to
      784.71 +/- 55.88 ng/ml when isolated), luteinizing hormone (from 0.84 +/- 0.09 to
      0.58 +/- 0.05 when in group and to 0.52 +/- 0.06 ng/ml when isolated) and
      prolactin (from 5.18 +/- 0.33 to 9.37 +/- 0.96 when in group and to 10.18 +/-
      1.23 ng/ml when isolated) secretion, but not in terms of follicle-stimulating
      hormone or testosterone secretion. The most important feature observed was that
      in each cage there was one animal with higher ACTH levels than the other two;
      furthermore, the exploratory behavior of this animal was different, indicating
      the occurrence of almost constant higher vigilance in this animal (latency to
      leave the den in group: 99.17 +/- 34.95 and isolated: 675.3 +/- 145.3 s). The
      data indicate that in each group there is an animal in a peculiar situation and
      its behavior can be detected by ACTH determination in addition to behavioral
      performance.

PMID- 15264027
TI  - Can calories from ethanol contribute to body weight preservation by malnourished
      rats?
AB  - Our objective was to compare the use of calories from ethanol by well-nourished
      and malnourished rats in terms of body weight. Female Wistar rats weighing 170
      180 g at the beginning of the study were used. The animals were divided into two
      groups (N = 12 each): group W received water ad libitum and group E an ethanol
      solution ad libitum as the only source of liquid throughout the experiment. The
      concentration of ethanol was increased weekly from 0 to 5, 10, 20 and 40% (v/v).
      In the well-nourished phase (A), all rats received food ad libitum (AW and AE).
      Ethanol treatment (AE) was then interrupted and water was offered to both groups.
      After 2 weeks both AW and AE rats were submitted to food restriction (50% of
      group AW food consumption), thus initiating the malnutrition phase (M). Liquid
      was offered as described before to the same W (MW) and E (ME) groups. The weight
      gain during the 1-week treatment of AE rats was similar to that of AW animals
      only when AE rats received the 5% (v/v) ethanol solution (9.16 vs 10.47 g).
      Weight loss was observed after exposure to 10% ethanol (P < 0.05) in spite of
      maintenance of caloric intake. Malnourished rats presented weight loss, which was
      attenuated by ethanol intake up to the 20% (v/v) solution and was related to an
      increased caloric offer. This effect was not observed with the 40% ethanol
      solution (-9.98 g). These data suggest that calories from ethanol were used to
      maintain body weight up to the concentration of 10% (v/v) (well-nourished) and
      20% (v/v) (malnourished) and that ethanol has a toxic profile which depends on
      nutritional status.

PMID- 15264028
TI  - Female novelty and the courtship behavior of male guinea pigs (Cavia porcellus).
AB  - In several rodent species, an increase or recovery of sexual behavior can be
      observed when sexually satiated males are placed in contact with a novel mate. In
      order to assess the influence of female novelty on the courtship behavior of
      guinea pigs (Cavia porcellus), four adult males were observed during four daily
      15-min sessions while interacting with the same pregnant female (same-female
      sessions). A new female was presented during the fifth session (switched-female
      session). The duration of behavioral categories was obtained from videotape
      records using an observational software. From the first to the second session,
      all males decreased the time allocated to investigating (sniffing and licking),
      following, and mounting the female, and that response did not recover by the end
      of the same-female sessions. No similar decreasing tendencies were detected in
      the circling or rumba categories. A marked increase of investigating occurred in
      all males from the last same-female session (8.1, 11.9, 15.1 and 17.3 percent
      session time) to the switched-female one (16.4, 18.4, 37.1 and 28.9 percent
      session time, respectively). Increases in following and circling were recorded in
      three of four males, and full-blown recovery of mounting in one male. No
      consistent changes in the females' responses to males (following or attacking)
      were observed throughout testing. These results are consistent with the
      hypothesis that guinea pig males recognize individual females and that courtship
      responses may suffer a habituation/recovery process controlled by mate novelty.

PMID- 15264029
TI  - The control of deliberate waiting strategies in a stop-signal task.
AB  - To inhibit an ongoing flow of thoughts or actions has been largely considered to
      be a crucial executive function, and the stop-signal paradigm makes inhibitory
      control measurable. Stop-signal tasks usually combine two concurrent tasks, i.e.,
      manual responses to a primary task (go-task) are occasionally countermanded by a
      stimulus which signals participants to inhibit their response in that trial (stop
      task). Participants are always instructed not to wait for the stop-signal, since
      waiting strategies cause the response times to be unstable, invalidating the
      data. The aim of the present study was to experimentally control the strategies
      of waiting deliberately for the stop-signal in a stop-task by means of an
      algorithm that measured the variation in the reaction times to go-stimuli on
      line, and displayed a warning legend urging participants to be faster when their
      reaction times were more than two standard deviations of the mean. Thirty-four
      university students performed a stop-task with go- and stop-stimuli, both of
      which were delivered in the visual modality and were lateralized within the
      visual field. The participants were divided into two groups (group A, without the
      algorithm, vs group B, with the algorithm). Group B exhibited lower variability
      of reaction times to go-stimuli, whereas no significant between-group differences
      were found in any of the measures of inhibitory control, showing that the
      algorithm succeeded in controlling the deliberate waiting strategies. Differences
      between deliberate and unintentional waiting strategies, and anxiety as a
      probable factor responsible for individual differences in deliberate waiting
      behavior, are discussed.

PMID- 15264030
TI  - Is avoidant disorder part of the social phobia spectrum in a referred sample of
      Brazilian children and adolescents?
AB  - The diagnosis of avoidant disorder was deleted from the Diagnostic and
      Statistical Manual of Mental disorders--fourth edition (DSM-IV) based on a
      'committee decision' suggesting that avoidant disorder is part of the social
      phobia spectrum. The objective of the present study was to examine the nature of
      this clinical association in a referred sample of Brazilian children and
      adolescents. We assessed a referred sample of 375 youths using semi-structured
      diagnostic interview methodology. Demographic (age at admission to the study and
      sex) and clinical (level of impairment, age at onset of symptoms and pattern of
      comorbidity) data were assessed in subsamples of children with avoidant disorder
      (N = 7), social phobia (N = 26), and comorbidity between both disorders (N = 24).
      Although a significant difference in the male/female ratio was detected among
      groups (P = 0.03), none of the other clinical variables differed significantly
      among subjects that presented each condition separately or in combination. Most
      of the children with avoidant disorder fulfilled criteria for social phobia.
      Thus, our findings support the validity of the conceptualization of avoidant
      disorder as part of the social phobia spectrum in a clinical sample.

PMID- 15264031
TI  - Expression of neuronal nitric oxide synthase in the developing superficial layers
      of the rat superior colliculus.
AB  - We investigated the level of expression of neuronal nitric oxide synthase (nNOS)
      in the retinorecipient layers of the rat superior colliculus during early
      postnatal development. Male and female Lister rats ranging in age between the day
      of birth (P0) and the fourth postnatal week were used in the present study. Two
      biochemical methods were used, i.e., in vitro measurement of NOS specific
      activity by the conversion of [3H]-arginine to [3H]-citrulline, and analysis of
      Western blotting immunoreactive bands from superior colliculus homogenates. As
      revealed by Western blotting, very weak immunoreactive bands were observed as
      early as P0-2, and their intensity increased progressively at least until P21.
      The analysis of specific activity of NOS showed similar results. There was a
      progressive increase in enzymatic activity until near the end of the second
      postnatal week, and a nonsignificant tendency to an increase until the end of the
      third week was also observed. Thus, these results indicated an increase in the
      amount of nNOS during the first weeks after birth. Our results confirm and extend
      previous reports using histochemistry for NADPH-diaphorase and
      immunocytochemistry for nNOS, which showed a progressive increase in the number
      of stained cells in the superficial layers during the first two postnatal weeks,
      reaching an adult pattern at the end of the third week. Furthermore, our results
      suggested that nNOS is present in an active form in the rat superior colliculus
      during the period of refinement of the retinocollicular pathway.

PMID- 15264032
TI  - Topographic aspects of photic driving in the electroencephalogram of children and
      adolescents.
AB  - The electroencephalogram amplitude spectra at 11 fixed frequencies of
      intermittent photic stimulation of 3 to 24 Hz were combined into driving
      "profiles" for 14 scalp points in 8 male and 7 female normal subjects aged 9 to
      17 years. The driving response varied over frequency and was detected in 70 to
      100% of cases in the occipital areas (maximum) and in 27 to 77% of cases in the
      frontal areas (minimum) using as a criterion peak amplitude 20% higher than those
      of the neighbors. Each subject responded, on average, to 9.7 +/- 1.15
      intermittent photic stimulation frequencies in the right occipital area and to
      6.8 +/- 1.97 frequencies in the right frontal area. Most of the driving responses
      (in relation to the previous background) were significant according to the
      spectral F-test (alpha = 0.05), which also detected changes in some cases of low
      amplitude responses not revealed by the peak criterion. The profiles had two
      maxima in the alpha and theta bands in all leads. The latter was not present in
      the background spectra in the posterior areas and was less pronounced in the
      anterior ones. The weight of the profile theta maximum increased towards the
      frontal areas where the two maxima were similar, while the profile amplitudes
      decreased. The profiles repeated the shape of the background spectra, except for
      the theta band. The interhemispheric correlation between profiles was high. The
      theta driving detected in all areas recorded suggests a generalized influence of
      the theta generators in prepubertal and pubertal subjects.

PMID- 15264033
TI  - Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used
      after myocardial revascularization.
AB  - Hemodynamic care during postoperative management of myocardial revascularization
      should include vasorelaxing drugs to insure adequate graft and coronary flow, and
      stimulation of stroke volume to maintain vascular perfusion pressure. We tested
      the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of
      diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10
      microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated
      human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a
      maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic
      relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation
      diltiazem depressed myocardial contractility and amrinone did not exhibit
      myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and
      dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat
      aorta. Norepinephrine-contracted human vessels were significantly more sensitive
      than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA =
      15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at
      concentrations still devoid of myocardial effects dobutamine and amrinone are
      effective dilators in graft segment vessels and rat aorta contracted by membrane
      depolarization. If the difference between aortic and myocardial tissue still
      holds in human tissues, at the appropriate concentrations these drugs should be
      expected to improve cardiac performance while still contributing to the
      maintenance of graft patency.

PMID- 15264034
TI  - Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells.
AB  - Patients expressing estradiol receptors in melanoma cells have been reported to
      have a better prognosis. We therefore decided to investigate the in vitro effects
      of beta-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel
      23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM beta-estradiol
      inhibited cell proliferation in 30% (0.70 +/- 0.03 x 10(5) cells) and increased
      tyrosinase activity in 50% (7130.5 +/- 376.5 cpm/10(5) cells), as compared to
      untreated cells (1.0 +/- 0.05 x 10(5) cells and 4769 +/- 25.5 cpm/10(5) cells,
      respectively). Both responses were completely (100%) blocked by 1 microM
      tamoxifen. Higher concentrations (up to 1.6 nM) or longer treatments (up to 72 h)
      did not result in a larger effect of the hormone on proliferation or tyrosinase
      activity. Competition binding assays demonstrated the presence of binding sites
      to [2,4,6,7-3H]-beta-estradiol, and that the tritiated analogue was displaced by
      the unlabeled hormone (1 nM to 100 microM, Kd = 0.14 microM, maximal displacement
      of 93%) or by 10 microM tamoxifen (displacement of 60%). Beta-estradiol also
      increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h
      treatment, as determined by Western blot. The absorbance of each band was 1.9-
      and 4-fold the controls, respectively, as determined with Image-Pro Plus
      software. Shorter incubation periods with beta-estradiol did not enhance
      phosphorylation; after 6-h treatment with the hormone, the two proteins returned
      to the control phosphorylation levels. The growth inhibition promoted by
      estradiol may explain the better prognosis of melanoma-bearing women as compared
      to men, and open new perspectives for drug therapy.

PMID- 15264035
TI  - Effect of strenuous maternal exercise before and during pregnancy on rat progeny
      renal function.
AB  - The effects of strenuous exercise before and during pregnancy on the renal
      function and morphological alterations of the progeny were determined in a study
      on female Wistar rats. This research was done based on a previous study carried
      out in our laboratory, which showed morphological alterations in rats submitted
      to this kind of exercise. As the form is related to the function, the
      physiological relevance of submitting a pregnant female to a high-intensity
      exercise training regimen could be explained by the fact that morphological
      alterations can influence kidney function. The animals were assigned to one of
      two groups: control animals that did not exercise during pregnancy and trained
      animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and
      daily for 60 min over a period of 8 weeks starting on the second day of
      pregnancy. Seven rats of each group were analyzed for morphological alterations
      and for renal function. The progeny of the rats used for morphological evaluation
      were born by cesarean section and the progeny of the animals used to evaluate
      renal function were born normally. The progeny were two months old when renal
      function was evaluated. Fertility and morbidity were the same for both groups.
      Strenuous maternal exercise had no significant influence on glomerular filtration
      rate (GFR) but renal plasma flow was lower in the progeny of the trained group
      (mean +/- SD, 16.65 +/- 3.77 ml min(-1) kg(-1)) compared to the progeny of the
      control group (33.42 +/- 2.56 ml min(-1) kg(-1)). Antidiuretic and
      antinatriuretic effects on the progeny of the trained group were observed, since
      urine flow as percentage of GFR and the fraction of urinary sodium excretion were
      lower in this group (1.38 +/- 0.10 and 0.60 +/- 0.04%, respectively) compared to
      the progeny of the control group (2.36 +/- 0.11 and 1.55 +/- 0.20%,
      respectively). Moreover, in this exercise program, fetuses from trained animals
      were small-sized (2.45 +/- 0.19 vs 4.66 +/- 2.45 g for control animals) and
      showed lower differentiation compared to fetuses from the control group. These
      effects were probably caused by caloric restriction, hypoxia and reduction of
      umbilical cord length.

PMID- 15264036
TI  - Follicle profile and plasma gonadotropin concentration in pubertal female ponies.
AB  - Twelve female ponies were examined daily for 30 days and classified as ovulating
      (OV; N = 6; 197 +/- 6 kg) or prepubertal (PP; N = 6; 196 +/- 9 kg). Follicles
      were detected by ultrasound and gonadotropins quantified by radioimmunoassay. The
      mean diameter of the largest follicles was significantly larger in OV (38 +/- 1
      mm) than in PP (26 +/- 2 mm) but there was no difference between groups in the
      size of the second largest follicle. There were more small follicles (<24 mm) in
      the PP than in the OV group, but PP fillies had a smaller number of follicles >29
      mm than the OV fillies. Follicle-stimulating hormone (FSH) levels did not differ
      between groups but PP fillies had lower luteinizing hormone (LH) peak (8 +/- 1
      ng/ml) and basal (4 +/- 0.5 ng/ml) levels, lower peak magnitude (2 +/- 0.2 ng/ml)
      and period average (5 +/- 0.6 ng/ml) than OV fillies (32 +/- 4.5, 8 +/- 1.2, 17.1
      +/- 6, and 15 +/- 2.3 ng/ml, respectively). The PP group, in contrast to the OV
      group, showed no relationship between FSH surge and follicle wave emergence. We
      conclude that an LH concentration higher than 8 ng/ml is needed for follicle
      growth to a preovulatory size. Wave emergence and FSH secretion seem to be
      independent events, probably due to an inhibitory neural system in these PP
      animals. PP fillies may provide a physiological model for the study of follicle
      wave emergence which apparently does not depend on gonadotropin levels.

PMID- 15264037
TI  - Hypercaloric cafeteria-like diet induced UCP3 gene expression in skeletal muscle
      is impaired by hypothyroidism.
AB  - The uncoupling protein UCP3 belongs to a family of mitochondrial carriers located
      in the inner mitochondrial membrane of certain cell types. It is expressed almost
      exclusively at high levels in skeletal muscle and its physiological role has not
      been fully determined in this tissue. In the present study we have addressed the
      possible interaction between a hypercaloric diet and thyroid hormone (T3), which
      are strong stimulators of UCP3 gene expression in skeletal muscle. Male Wistar
      rats weighing 180 +/- 20 g were rendered hypothyroid by thyroidectomy and the
      addition of methimazole (0.05%; w/v) to drinking water after surgery. The rats
      were fed a hypercaloric cafeteria diet (68% carbohydrates, 13% protein and 18%
      lipids) for 10 days and sacrificed by decapitation. Subsequently, the
      gastrocnemius muscle was dissected, total RNA was isolated with Trizol and UCP3
      gene expression was determined by Northern blotting using a specific probe.
      Statistical analysis was performed by one-way analysis of variance (ANOVA)
      followed by the Student-Newman-Keuls post-test. Skeletal muscle UCP3 gene
      expression was decreased by 60% in hypothyroid rats and UCP3 mRNA expression was
      increased 70% in euthyroid cafeteria-fed rats compared to euthyroid chow-fed
      animals, confirming previous studies. Interestingly, the cafeteria diet was
      unable to stimulate UCP3 gene expression in hypothyroid animals (40% lower as
      compared to euthyroid cafeteria-fed animals). The results show that a
      hypercaloric diet is a strong stimulator of UCP3 gene expression in skeletal
      muscle and requires T3 for an adequate action.

PMID- 15264038
TI  - CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells.
AB  - T-type Ca2+ channels are important for cell signaling by a variety of cells. We
      report here the electrophysiological and molecular characteristics of the whole
      cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV
      was described by a single exponential function with a time constant of 18.32 +/-
      1.87 ms (N = 16). The I-V relationship measured with Ca2+ as a charge carrier was
      shifted to the left when we applied a conditioning pre-pulse of up to -120 mV,
      indicating that a low voltage-activated current may be present in GH3 cells.
      Transient currents were first activated at -50 mV and peaked around -20 mV. The
      half-maximal voltage activation and the slope factors for the two conditions are 
      35.02 +/- 2.4 and 6.7 +/- 0.3 mV (pre-pulse of -120 mV, N = 15), and -27.0 +/-
      0.97 and 7.5 +/- 0.7 mV (pre-pulse of -40 mV, N = 9). The 8-mV shift in the
      activation mid-point was statistically significant (P < 0.05). The tail currents
      decayed bi-exponentially suggesting two different T-type Ca2+ channel
      populations. RT-PCR revealed the presence of alpha1G (CaV3.1) and alpha1I
      (CaV3.3) T-type Ca2+ channel mRNA transcripts.

PMID- 15264039
TI  - [Hepatosplenic schistosomiasis mansoni: a tragic disease].

PMID- 15264041
TI  - [Arterial anatomy of the sigmoid colon useful for colon take down techniques].
AB  - BACKGROUND: An anatomic study about the arterial vascularization of the sigmoid
      was performed in order to obtain guidelines for the surgical treatment of rectal
      carcinoma. AIM: In the proposed technique, the sigmoid is brought down to the
      perineum, after radical anal-rectal resection, including sphincterectomy.
      MATERIAL AND METHODS: Thirty-three anatomical pieces were obtained through in
      situ dissection of formolized corpses (22 were male and 11 female). Turpentine
      solution, red marking, polyvinyl chloride were the materials used for preparation
      after catheterization of the inferior mesenteric artery. RESULTS: The inferior
      mesenteric artery originated in most cases from the left side of the abdominal
      aorta, approximately 4.3 cm fromits bifurcation point; the left colonic artery,
      in 25 cases, originated straight from the inferior mesenteric artery below the
      left colonic artery, after which the sigmoid would be brought down to the
      perineum. CONCLUSION: Knowledge about arterial vascularization of the sigmoid
      could be helpful in the surgical management of rectal cancer.

PMID- 15264040
TI  - [Schistosomal portal hypertension: influence of the portal blood flow in serum
      levels of hepatic enzymes].
AB  - AIM: To evaluate relation between the portal blood flow and the laboratory
      hepatic screening in patients with schistosomal portal hypertension. PATIENTS AND
      METHODS: Sixty-four patients with schistosomal portal hypertension had studied,
      being 19 not operated, 23 submitted to esophagogastric devascularization with
      splenectomy and 22 submitted to distal splenorenal shunt. Evaluated the
      laboratory hepatic screening through the dosage of albumin, aspartate
      aminotransferase, alanine aminotransferase, direct bilirubin and indirect
      bilirubin, alkaline phosphatase, gamma-glutamil transferase and prothrombin time.
      The portal flow was evaluated for Doppler. The results have been analyzed through
      linear regression, Pearson correlation coefficient, chi-square and one-way
      analysis of variance with Tukey's test. RESULTS: It was proven that only gamma
      glutamil transferase had significant correlation with the portal flow. In compare
      of the quartiles, also only gamma-glutamil transferase showed resulted
      significant, it was evidenced that the fourth quartile, that is bigger portal
      flow and formed in its majority for patients not operated, also was bigger
      average of gamma-glutamil transferase and significantly bigger value than first
      and the third quartiles. CONCLUSIONS: 1. The portal blood flow was bigger in
      patients that the serum level of GGT was bigger; 2. the gamma-glutamil
      transferase is the variable of the hepatic screening evaluation more
      representative of the portal flow influence in hepatic functional activity in
      patients with hepatosplenic schistosomiasis, and 3. probably, the different
      surgeries through hemodynamics modifications, are beneficial in to diminish the
      degree of cholestasis or in decrease the microssomal induction.

PMID- 15264042
TI  - [Solitary diverticulum of the cecum: experience of a Brazilian general hospital].
AB  - BACKGROUND: Cecal diverticulitis is a rare condition, specially in western
      people. Its importance concerns of being part of the differential diagnosis of
      acute appendicitis and ulcerated cecal carcinoma. AIM: To present the experience
      of southern Brazilian general hospital in the treatment of cecal diverticulitis.
      MATERIAL AND METHODS: We present four cases of single inflamed cecal
      diverticulum. One was diagnosed by pre-operatively computer tomography and was
      treated medically without complications. The other three cases were diagnosed
      during operation and treated by right hemicolectomy and ileotransverse
      anastomosis. RESULTS: There were no deaths or complications. When cecal
      diverticulitis is pre-operatively diagnosed it may be treated medically. We
      preclude laparotomy when the diagnosis is uncertain. CONCLUSION: We recommend
      radical surgical management when the diagnosis is made during operation.

PMID- 15264043
TI  - [Specialized intestinal metaplasia of the distal esophagus in gastroesophageal
      reflux disease: prevalence and clinico-demographic features].
AB  - BACKGROUND: Specialized intestinal metaplasia can be categorized according
      endoscopic and histological findings in long segment Barrett, short segment
      Barrett and specialized intestinal metaplasia of cardia. Barrett's esophagus is
      an acquired disease that is found in about 10%-13% of patients undergoing
      endoscopy for symptoms of gastroesophageal reflux disease and it is well
      established as predisposing to esophageal adenocarcinoma. The columnar epithelium
      with goblet cells replaces the normal squamous epithelium. OBJECTIVE: To
      determine the prevalence and clinical-demographic characteristics of specialized
      intestinal metaplasia of distal esophagus in the gastroesophageal reflux disease.
      METHODS: From April to October 2002, 402 patients referred to upper endoscopy due
      gastroesophageal reflux disease were evaluated through of a symptom questionnaire
      about clinical and demographic features and submitted to upper endoscopy with
      four-quadrant biopsies 1 cm below escamocolumnar junction. RESULTS: Eighteen
      point four percent of patients had specialized intestinal metaplasia, 0.5% long
      segment Barrett esophagus, 3.2% short segment Barrett's esophagus and 14.7%
      specialized intestinal metaplasia of cardia. Patients with Barrett's esophagus
      showed a tendency to be male and specialized metaplasia of cardia to be female.
      All patients with Barrett's esophagus were white. There was not association
      between symptoms of gastroesophageal reflux disease and specialized intestinal
      metaplasia, but patients with Barrett's esophagus showed a tendency to have
      symptoms over 5 years and had more hiatal hernia and esophagitis. The use of
      alcohol and tobacco was not related to the presence of specialized intestinal
      metaplasia. CONCLUSIONS: Barrett's esophagus was more related to the male gender,
      gastroesophageal reflux disease symptoms for 5 years or longer, more intense
      esophagitis and hiatal hernia, but was not related to the use of tobacco and
      alcohol.

PMID- 15264044
TI  - [Interferon-alpha and ribavirin therapy on chronic hepatitis C virus infection:
      the experience of Rio Grande do Sul State Health Department, Brazil].
AB  - BACKGROUND: Chronic infection by hepatitis C virus is an important public health
      issue. AIMS: To assess the effectiveness of a combination therapy with interferon
      alpha plus ribavirin and to identify predictive factors of response in adult
      patients with chronic hepatitis C in a public drug supply program. PATIENTS AND
      METHODS: A retrospective study of consecutive records of 400 patients with
      chronic hepatitis C treated with interferon-a plus ribavirin therapy, as part of
      a health program conducted by the Department of Health of the State of Rio Grande
      do Sul, Porto Alegre, RS, southern Brazil, between 1999 and 2000, was carried
      out. RESULTS: Sex distribution was similar, and the average age was 46.5 +/- 10.3
      years. Response at the end of the treatment was observed in 49% of patients, and
      sustained response was observed in 32% of them. Sustained response was
      significantly higher in females and in patients infected by genotypes other than
      1. We did not observe significant differences in terms of age or histological
      stage and activity score. CONCLUSION: In adult patients with chronic hepatitis C,
      combination therapy with interferon-alpha plus ribavirin was effective in one
      third of patients. Higher rates of response were observed in women and in
      patients infected by genotypes other than 1.

PMID- 15264045
TI  - [Validity of serum amylase and lipase in the differential diagnosis between
      acute/acutized chronic pancreatitis and other causes of acute abdominal pain].
AB  - BACKGROUND: Raised serum amylase and lipase levels are observed in several
      abdominal diseases. AIM: Assessing the validity of serum amylase and lipase for
      the differential diagnosis between acute pancreatitis/acutized chronic
      pancreatitis, biliary tract disease, perforated gastroduodenal ulcer and acute
      appendicitis. PATIENTS E METHODS: Prospective study including 134 individuals: 38
      with acute pancreatitis/acutized chronic pancreatitis, 35 with biliary tract
      disease, 17 with perforated gastroduodenal ulcer and 44 with acute appendicitis,
      mean age (standard deviation) of 42.4 +/- 17.7, 46.7 +/- 18.3, 47.8 +/- 12 and
      33.7 +/- 17.8 years, respectively. Serum amylase and lipase were determined at
      admission to the emergency department. RESULTS: For the diagnosis of acute
      pancreatitis/acutized chronic pancreatitis, when the cutt-off levels of serum
      amylase were set at the upper normal range level or up to 5-fold as high, the
      sensitivity decreased from 92% to 74%, the specificity increased from 85% to 99%,
      the positive predictive value increased from 71% to 97%, and the negative
      predictive value decreased from 96% to 91%. For serum lipase levels similar
      figures were obtained for sensitivity and negative predictive value, but the
      specificity and positive predictive value were lower. When the combination of
      raised serum amylase or lipase were analyzed, a minor increase was observed in
      sensitivity and negative predictive value. CONCLUSIONS: For the diagnosis of
      acute pancreatitis/acutized chronic pancreatitis: 1) the best cut-off level for
      both tests was 2-times the upper normal range; 2) the sensitivities of serum
      amylase and lipase were similar; 3) the specificity and positive predictive value
      of serum amylase were slightly higher than observed for serum lipase; 4) the
      sensitivity but not the specificity increased when at least one between amylase
      or lipase was raised.

PMID- 15264046
TI  - [Risk factors for persistent diarrhea in infants].
AB  - BACKGROUND: Persistent diarrhea is a multicausal disease. The analysis of risk
      factors for persistent diarrhea includes environmental and biological variables
      as well as therapeutical management. AIM: To identify risk factors for persistent
      diarrhea among children hospitalized with acute diarrhea. PATIENT AND METHODS:
      This is a case-control study. The sample consisted of 212 infants under 24
      months, hospitalized with acute diarrhea, at the "Instituto Materno-Infantil de
      Pernambuco", Recife, PE, Brazil. Cases were infants with persistent diarrhea and
      controls those with acute diarrhea. Cases and controls were compared to a series
      of socio-economic, biological and clinical variables, previous morbidities and
      therapeutic management prior to hospital admission. Unadjusted and adjusted odds
      ratio were used with the respective 95% confidence intervals. It was adopted the
      level of significance of 5%. Logistic regression analysis was conducted to
      control for potential confounding factors. RESULTS: The risk of persistent
      diarrhea was higher for infants with: dysentery, fever at the onset of diarrhea,
      fasting and taking antibiotics prior to hospital admission. The variables that
      showed the highest adjusted odds ratios for persistent diarrhea were infants
      living in households without refrigerator and perianal hyperemia at hospital
      admission. CONCLUSIONS: The improvement of environmental conditions and an
      adequate clinical management of diarrhea for hospitalized infants may contribute
      to the reduction of diarrhea morbidity.

PMID- 15264047
TI  - Growth assessment in children with extra-hepatic portal vein obstruction and
      portal hypertension.
AB  - BACKGROUND: Several studies carried out to examine the growth of children with
      extra-hepatic portal vein obstruction and portal hypertension have reported a
      variety of findings. AIM: To assess anthropometric indices in children with
      portal hypertension due to extra-hepatic portal vein obstruction and who were
      treated by endoscopic variceal sclerotherapy. METHODS: Anthropometric data were
      obtained retrospectively from the medical records of 24 patients who had been
      followed for 3.8 +/- 2.5 years at the Pediatric Gastroenterology Outpatient
      Clinic of the University Hospital, Campinas, SP, Brazil. The mean Z scores of
      weight for age, height for age and body mass index at diagnosis and at the last
      consultation were compared to reference data of the National Center for Health
      Statistics. The two recordings were compared to assess the long-term effect of
      the condition. RESULTS: The mean Z scores at diagnosis and at the last follow-up
      visit were all within normal ranges when compared to the reference population,
      with the following respective values: weight for age, 0.042 +/- 1.09 and 0.132 +/
      1.29; height for age, 0.200 +/- 1.04 and 0.466 +/- 1.24, and body mass index, 
      0.223 +/- 0.98 and -0.198 +/- 0.98. In addition, there were no significant
      differences between the Z score values obtained in the two recordings.
      CONCLUSION: Portal hypertension due to extra-hepatic portal vein obstruction was
      not associated with growth impairment in the group of children studied.

PMID- 15264048
TI  - Giant retroperitoneal lipoma: a case report.
AB  - BACKGROUND: Retroperitoneal lipoma is an extremely rare neoplasm. AIMS: The
      authors report a case of giant retroperitoneal lipoma in a 32-year-old white
      female, with a history of pain and an abdominal mass over a 2-year period. Total
      abdominal ultrasonography and barium enema showed a large mass located in the
      retroperitoneal space behind the ascending colon. Laparotomy showed a large
      encapsulated tumor measuring 20 x 13 x 10 cm and weighing 3.400 g. The
      histological study revealed a benign neoplasm of fatty cells. CONCLUSION: The
      patient remains well 17 years after surgery, without recurrence of the disease.

PMID- 15264049
TI  - Molecular aspects of esophageal squamous cell carcinoma carcinogenesis.
AB  - BACKGROUND: The development of human esophageal cancer is a multistep,
      progressive process. An early indicator of this process is an increased
      proliferation of esophageal epithelial cells morphologically including basal cell
      hyperplasia, dysplasia, carcinoma in situ and advanced esophageal squamous cell
      carcinoma. The process of tumorigenesis at cellular level is related to disorders
      of the control of cell proliferation and differentiation and controlled cell
      death (apoptosis). Most of cancer cells contain genetic alterations related to
      the control of these processes, including transcription factors and apoptosis
      related proteins. AIM: In this review, the current knowledge of the genetic
      profile of this subtype of esophageal tumor is discussed, focusing on the
      potential of the development of novel tools for clinical management of esophageal
      squamous cell carcinoma. CONCLUSIONS: The advances in the field of molecular
      biology have let us to deeper our knowledge of the process of carcinogenesis of
      esophagus. Ideally, this knowledge should be translated in benefits for patients
      suffering from cancer. Thus, better understanding of molecular alterations during
      carcinogenesis is expected to improve tumor control and prevention and also may
      lead to better disease management.

PMID- 15264050
TI  - Clinical and endoscopic evaluation of gastroesophageal reflux disease in patients
      successfully treated with esomeprazole.
AB  - BACKGROUND: Esomeprazole, an S-isomer of omeprazole, is the first proton pump
      inhibitor developed as an optical isomer, and it has shown high healing rates in
      erosive esophagitis. AIM: To evaluate the efficacy and tolerability of
      esomeprazole in subjects with erosive esophagitis, according to the Los Angeles
      classification study design: an open, multi-center clinical study. MATERIAL AND
      METHODS: Two hundred and eighteen subjects with reflux esophagitis confirmed by
      endoscopy were included in an open, multi-center study in Brazil. All of them
      received esomeprazole 40 mg, once daily, for a 4-week period. Subjects who had
      unhealed esophagitis by week 4 continued the treatment for another 4 weeks. The
      primary efficacy endpoint was the healing rates by weeks 4 and 8. The secondary
      endpoints were the number of patients with symptom resolution by week 4, the
      number of days to sustained symptom resolution, number of symptom-free days and
      nights and safety and tolerability of the drug. RESULTS: Healing rates by weeks 4
      and 8 were 82% (confidence interval: 77.4%-87.6%) and 96.1% (confidence interval:
      93.5% - 98.8%), respectively. Ninety-nine (99%) of the patients had heartburn
      resolution by week 2. The most common adverse events were headache (4%), diarrhea
      (2.6%) and epigastric pain (2.2%). CONCLUSION: For the studied period,
      esomeprazole was shown to be a safe and well-tolerated drug, providing
      significant healing rates of mucosal breaks, regardless of LA classification, in
      patients with erosive esophagitis. Esomeprazole was also shown to be effective in
      quickly relieving symptoms.

PMID- 15264051
TI  - [Standardization of techniques and equipment for vascular ultrasonography exams
      ].

PMID- 15264052
TI  - Vitamin A palmitate photostability and stability over time.
AB  - Vitamin A palmitate photostability in relation to UVA and UVB was tested in
      hydroxy ethyl cellulose hydrogels at pH 4.0, 5.6, 7.0, and 8.0, alone and with
      the addition of sunscreens (3,4-methylbenzilidencamphor or butyl methoxy
      dibenzoylmethane) or an antioxidant (butylated hydroxy toluene). The
      photostability of vitamin A palmitate was also tested in encapsulated systems
      (Tagravit A1 microcapsules, Lipotec liposomes, phosphatidylcholine liposomes, and
      Lipotec nanocapsules) dispersed in gels at pH 5.6 and 7.0. The stability of
      retinyl palmitate over time in hydroxy ethyl cellulose hydrogels at pH 5.6 and
      7.0 (stored one month at 25 degrees C or 40 degrees C), alone or with butylated
      hydroxy toluene, was also tested. The stability of retinyl palmitate over time in
      encapsulated systems, dispersed in gels at pH 5.6 and 7.0, was also studied. O/W
      emulsions were also prepared to compare the stability of vitamin A palmitate
      introduced in a lipophilic/hydrophilic medium (O/W emulsions) and a hydrophilic
      medium (hydrogels). HPLC analysis showed that encapsulated systems such as
      Lipotec nanocapsules, Tagravit A1 microcapsules, phosphatidylcholine liposomes,
      and Lipotec liposomes protect the vitamin A ester over time from hydrolysis and
      from oxidation to retinaldeide and retinoic acid, and that Lipotec nanocapsules
      and phosphatidylcholine liposomes also improve the vitamin's photostability. A
      change in pH (from 5.6 to 7.0) of the gels did not influence the vitamin ester's
      stability. pH levels of 4.0 and 8.0 determined a decrease in the stability of
      retinyl palmitate in the gels. A high concentration of sunscreens improved the
      photostability of retinyl palmitate in the gels at pH 5.6 and 7.0. Butylated
      hydroxy toluene protected retinyl palmitate from degradation induced by light at
      all the pH levels studied and by heat at pH 5.6 and 7.0, as can be seen from the
      study of the photostability of vitamin A palmitate under UVB and UVA and of
      stability over time. Rheological studies showed a slight decrease in the
      viscosity of the gels after UVB-UVA irradiation and a higher decrease in the
      viscosity of the gels and the emulsions after storage at 25 degrees C and 40
      degrees C. This decrease can be attributed to a partial degradation of hydroxy
      ethyl cellulose and of emulsifier, as can be seen from the decrease in shear
      stress versus shear rate values under these conditions of storage, denoting a
      depolymerization of the rheological modifier.

PMID- 15264053
TI  - Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation
      study.
AB  - The basic properties and the in vitro release rate kinetics of azelaic acid (AA),
      alternatively vehiculated in different phospholipid-based vesicles such as
      ethosomes or liposomes, were investigated. Ethosomes were produced by a simple
      method based on addition of an aqueous phase to an ethanol solution (comprised
      between 20?% and 45%, v/v) of soy phosphatidyl choline (5%, w/w) and AA (0.2%,
      w/w) under mechanical stirring. Liposomes were obtained by the same composition
      in the absence of ethanol with the reverse-phase evaporation method. Vesicle size
      was measured by photon correlation spectroscopy (PCS), evidencing smaller mean
      diameters and narrower dimensional distributions in the case of ethosomes with
      respect to liposomes. In order to obtain homogeneously sized vesicles, both
      ethosomal and liposomal dispersions were extruded through polycarbonate membranes
      with pores of calibrated diameter (400 nm and 200 nm). Vesicle morphology was
      characterized by freeze-fracture scanning electron microscopy (SEM) showing the
      presence of unilamellar vesicles both in liposome- and in ethosome-based
      dispersions. Free energy measurements of the vesicle bilayers were conducted by
      differential scanning calorimetry (DSC). AA diffusion from ethosomal or liposomal
      dispersions and from ethosomes and liposomes incorporated in a viscous gel was
      investigated by a Franz cell assembled with synthetic membranes. The release rate
      was more rapid from ethosomal systems than from liposomal systems. In particular,
      ethosomes produced by the highest ethanol concentration released AA more rapidly,
      and the same trend was found using viscous forms.

PMID- 15264054
TI  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of the
      application of a cationic conditioner to "clean" hair.
AB  - In this study the applicability of the surface-sensitive ToF-SIMS technique to
      hair analysis and associated aqueous processing is evaluated. ToF-SIMS analysis
      of "as received" human hair indicates the presence of silicones, anionic
      surfactants, and cationic conditioners, from previous treatments, on the fiber
      surface. Cleaning of the hair with SLS or SLES results in adsorption of the
      surfactants onto the fiber surface. In particular, the more non-polar surfactant
      components have greater substantivity for the fiber surface, as indicated by the
      relative increase in their ToF-SIMS intensity. Application of the Incroquat
      Behenyl 18-MEA conditioner to both "virgin" and bleached hair results in the
      adsorption of the cationic C18, C20, C22, and C21 surfactant components onto the
      hair surface. The ToF-SIMS data indicate higher levels of conditioner on the
      bleached hair relative to the undamaged hair.

PMID- 15264055
TI  - Investigation of atmospheric oxidation of propyl gallate in an anionic surfactant
      system in the absence and presence of ascorbic acid.
AB  - The antioxidant efficiency of two hydrophilic species, ascorbic acid (AA) and
      propyl gallate (PG), in an anionic surfactant system are studied. Ascorbic acid
      and propyl gallate are dissolved/solubilized in a microemulsion formed by water,
      pentanol, and sodium dodecyl sulfate. The determination of propyl gallate
      decomposition/oxidation kinetics shows enhanced oxidation of PG with increasing
      pentanol concentration in the system. When ascorbic acid and propyl gallate are
      both present in water, in surfactant aqueous solution, and in the studied
      microemulsion systems, the molecular complex AAPG is formed. After some time the
      complex decomposes.

PMID- 15264056
TI  - A study of the photolightening mechanism of blond hair with visible and
      ultraviolet light.
AB  - In this study the photolightening behavior of blond hair was investigated. The
      results demonstrated that visible (VIS) and ultraviolet (UV) light lighten blond
      hair through different mechanisms. VIS light was found to contribute much more to
      the lightening of blond hair than UV light, and acted directly, while UV light
      only lightened blond hair that had been washed following irradiation. VIS and UV
      light both, however, lightened to a similar degree isolated melanin granules and
      decomposed melanin granules that were exposed on a cross section of blond hair.
      These results indicate that melanin granules are equally sensitive to both forms
      of light while blond hair is most sensitive to VIS light. The results also
      indicate that hair tissues, excluding melanin granules, are damaged by UV light
      but not by VIS light. Based on these facts, the hypothetical lightening mechanism
      of UV light is assumed to be that UV light preferentially attacks and damages
      hair tissues rather than melanin granules. This occurs only after the hair is
      washed, as the washing process removes the melanin granules that effuse from
      loose hair fibers. In contrast, VIS light preferentially attacks and decomposes
      the melanin granules rather than other tissues, and also results in the
      lightening of blond hair but without the need for subsequent washing. We also
      found that while VIS light destroys the structure of isolated melanin granules,
      UV light does not act in a similar manner. Consequently, it is proven that VIS
      and UV light attack different sites of the melanin granule, even though the
      lightening rates from both light sources are similar.

PMID- 15264060
TI  - [Abstracts of the XX Pneumology Congress].

PMID- 15264106
TI  - Immunogenicity of recombinant human proteins: causes and consequences.
AB  - Antibodies develop to varying degrees during treatment with human proteins,
      including insulin, growth hormone, granulocyte-macrophage colony-stimulating
      factor, factor VIII, erythropoietin, and interferons. These antibodies may reduce
      the clinical efficacy of these agents by blocking or neutralizing their biologic
      activity and may have other biologic effects. For example, antibodies develop in
      20 % to 40% of patients with severe hemophilia treated with human factor VIII;
      the presence of these antibodies can result in tolerance to the clotting effects
      of this agent. Similarly, a proportion of patients treated with interferon alpha
      develop antibodies, which inhibit its therapeutic effects. Therefore, it is
      important to test for neutralizing antibodies during treatment with these agents,
      particularly in patients who are unresponsive to treatment or have breakthrough
      disease. This article reviews the incidence and clinical impact of antibodies
      that develop in response to some of the commonly used protein therapeutic agents.

PMID- 15264107
TI  - Biologic role of interferon beta in multiple sclerosis.
AB  - The mode of action of interferon-beta (IFNbeta) as a therapeutic agent for
      multiple sclerosis is still insufficiently elucidated. Of the known
      immunomodulatory effects of IFNbeta, those that seem important are its [1]
      effects on the production of cytokines by T helper lymphocytes, [2] antagonistic
      effect against some of the proinflammatory and immunoregulatory effects of
      IFNgamma, [3] inhibitory effect on resistance of T lymphocytes to apoptotic
      signals, [4] inhibitory effect on the production of matrix metalloproteases, and
      [5] modulatory effect on the expression of adhesion molecules and chemokines. The
      relative importance of each of these actions is presently unknown, and still
      other actions of IFNbeta may be at play. The possibility that therapeutic IFNbeta
      compensates for a lack of endogenous IFNbeta production is discussed.

PMID- 15264108
TI  - Immunogenicity of interferon beta: differences among products.
AB  - Protein-based therapies are useful in a variety of diseases; however, their
      potential for immunogenicity is a disadvantage. Neutralizing antibodies (NAbs)
      that develop to interferon beta (IFNbeta) products (IFNbeta-1b, IFNbeta-1a
      Avonex((R)), or IFNbeta-1a-Rebif((R))), which are first-line therapies for the
      treatment of multiple sclerosis, are reported to reduce the clinical efficacy of
      these agents. In individual clinical studies of each commercially available
      IFNbeta product, 28% to 47% of patients develop NAbs to IFNbeta-1b, 12% to 28 %
      to IFNbeta-1a-Rebif, and 2% to 6% to IFNbeta-1a-Avonex. Problems exist in
      comparing the incidence of NAbs among IFNbeta products across studies because of
      differences in study methodology, including assay methods, treatment duration,
      and the definition of NAb positive. Results from studies that have directly
      compared these products are consistent with results from the respective clinical
      trials of IFNbetas. Both the clinical trials and the independent studies have
      shown that NAbs develop more frequently with IFNbeta-1b treatment than with
      IFNbeta-1a treatment and that, among IFNbeta-1a products, NAbs develop more
      frequently with IFNbeta-1a-Rebif treatment than with IFNbeta-1a-Avonex treatment.
      Factors that may affect the immunogenicity of IFNbetas, including the dosing
      regimens and the biochemical properties of the products, are discussed.

PMID- 15264109
TI  - Impact of neutralizing antibodies on the clinical efficacy of interferon beta in
      multiple sclerosis.
AB  - Neutralizing antibodies (NAbs) can develop in a large proportion of patients with
      MS who receive treatment with interferon beta (IFNbeta). Data show that IFNbeta
      1b is more immunogenic than IFNbeta-1a and that IFNbeta-1a-Rebif((R)) is more
      immunogenic than IFNbeta-1a-Avonex((R)). This article reviews the long-term data
      from large phase III clinical trials showing that NAbs can reduce the clinical
      efficacy of IFNbeta in patients with MS; patients who have a positive result on
      NAb testing have a higher relapse rate and more disease activity, as measured by
      brain MRI, than do patients with a negative result. The detrimental effects of
      NAbs were not observed until after 18 months of treatment, suggesting that short
      term clinical trials cannot adequately assess the efficacy of IFNbeta products in
      MS. Clinicians should consider the possible development of NAbs when starting
      patients on treatment and in patients with disease progression while on IFNbeta
      treatment.

PMID- 15264110
TI  - Measurement of neutralizing antibodies to interferon beta in patients with
      multiple sclerosis.
AB  - Treatment of multiple sclerosis (MS) with interferon beta (IFNbeta) can be
      associated with the development of binding antibodies (BAbs) and neutralizing
      antibodies (NAbs). NAbs are a subset of BAbs that prevent IFNbeta from
      effectively binding to or activating its receptor, thereby blocking its biologic
      effects and inhibiting its therapeutic effects. Several factors can affect the
      incidence and titers of NAbs that develop to IFNbeta, including the type of
      IFNbeta preparation used for treatment. One of the major limitations to
      evaluating the relative importance of these factors is the variation in assays
      used to detect IFNbeta antibodies. Two major types of assays are used to detect
      antibodies to IFNbetas: [1] binding assays, which measure the ability of
      antibodies in patients' sera to bind to IFNbeta; and [2] neutralization assays
      (or bioassays), which measure the ability of patients' sera to neutralize the
      biologic effects of IFNbeta. Assays used to detect NAbs differ in their
      sensitivity and specificity, and there can be high variability between
      laboratories in how these assays are performed (e. g., types of cells, quantity
      of IFNbeta). This article reviews assays currently used for detecting NAbs to
      IFNbeta and discusses the development of an international standard NAb assay. The
      myxovirus resistance protein A (MxA) assay is recommended as the standard assay
      for the quantification of NAbs providing availability of reagents.

PMID- 15264111
TI  - Assessment and management of neutralizing antibodies in patients with multiple
      sclerosis.
AB  - The development of neutralizing antibodies (NAbs) to interferon beta (IFNbeta)
      products during treatment of MS poses a challenge for clinicians. Given the
      impact of NAbs on the clinical efficacy of IFNbetas, the immunogenicity of
      different IFNbeta products should be one of the factors that neurologists
      consider in the treatment of patients with MS. However, no clear guidelines are
      available for the practicing neurologist concerning which patients should be
      tested for NAbs and how to clinically manage patients who develop NAbs. This
      article summarizes the content of this supplement, discusses issues related to
      measuring NAbs in clinical practice, and gives practical alternatives for
      managing MS in patients who develop NAbs during IFNbeta therapy.

PMID- 15264113
TI  - Breaking the tolerance or the virus?

PMID- 15264114
TI  - Effect of interferon treatment on glucose metabolism in children with chronic
      hepatitis B infection.
AB  - BACKGROUND/AIMS: Interferon is known to have some effects on glucose metabolism,
      but this issue has not been investigated in children with chronic hepatitis B
      infection. The aim of this study was to investigate the impact of interferon on
      glucose metabolism and to investigate whether autoimmunity has a role in the
      pathogenesis. METHODS: Fourteen patients (9 male, 6.3+/-2.7 years) with children
      with chronic hepatitis B infection were prospectively evaluated. They received
      interferon 10 MU/m2 for six months. Vral glucose tolerance test, fasting insulin
      and C-peptide, postprandial insulin and C-peptide, anti-GAD antibody, HOMA-IR and
      glucose/insulin ratio were measured before and after treatment. RESULTS: Before
      interferon, oral glucose tolerance test showed glucose intolerance in two
      patients (14.5%) and hypoglycemia in one patient (7.1%). One patient had
      hyperinsulinemia and insulin resistance (7.1%), and four patients had
      hypoinsulinemia and insulin hypersensitivity (28.5%). After interferon, oral
      glucose tolerance test was normal in 13 patients (92.8%). Abnormal oral glucose
      tolerance test persisted in the same patient, but no difference was found in
      insulin resistance. Hypoinsulinemia and insulin hypersensitivity were present in
      five patients (35.7%). DM related autoantibodies were negative in all patients
      before interferon; however, one patient, whose glucose metabolism was within
      normal limits, developed anti-GAD antibody after interferon. CONCLUSIONS:
      Children with children with chronic hepatitis B infection were shown to have
      hypoinsulinemia and insulin hypersensitivity. These children may have risk of
      progresssing to insuline dependent drabetes mellitus. We demonstrated that
      interferon did not seem to worsen glucose metabolism, but it had minimal positive
      impact on it. These results should be supported with other studies and interferon
      should be used carefully, especially in children with decreased beta cell
      reserve.

PMID- 15264115
TI  - Hepatitis B carriage and Brucella seroprevalence in urban and rural areas of Bolu
      province of Turkey: a prospective epidemiologic study.
AB  - BACKGROUND/AIMS: In this study, we aimed to investigate the prevalence of
      hepatitis B surface antigen positivity and antibodies against Brucella in rural
      and urban areas of Bolu province of Turkey. METHODS: A total of 4,234 [corrected]
      people were screened from the urban and rural regions (3084 [corrected] versus
      1150, respectively). All sera were evaluated for HBsAg and Brucella antibody.
      RESULTS: HBsAg, rose bengal and serum tube agglutination positivity were found to
      be 2.85%, 1.0%, 0.46%, respectively, in the urban area, versus 2.6%, 1.7%, 1.1%,
      respectively, in rural areas (P>0.05). CONCLUSIONS: HBsAg seropositivity in Bolu
      is lower than in many other centers in Turkey. Brucella prevalence is 1%, which
      is higher than that in the Ministry of Health records. This shows that the
      recording system in our country is not very efficient. Similar studies should be
      carried out in different regions of our country to determine the actual values,
      which requires the cooperation of scientific foundations and the Ministry of
      Health.

PMID- 15264116
TI  - A three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients
      with normal aminotransferase levels.
AB  - BACKGROUND/AIMS: HBeAg-positive patients with normal ALT levels are unlikely to
      respond to current therapy. In addition, there is a high risk of hepatocellular
      carcinoma in HBeAg-positive patients in the natural course of HBV infection. For
      this purpose, we aimed to investigate the clinical efficacy and safety of a three
      month course of lamivudine therapy in HBeAg-positive hepatitis B patients with
      normal aminotransferase levels for assessing a more practical and economical
      approach to these patients. METHODS: Forty-six patients were prospectively
      randomized into two groups. Group A consisted of 13 patients treated with
      lamivudine 100 mg/day, for 12 weeks [7 males, mean age 23.30+/-5.82 years, median
      ALT of 27 IU/L (21-40), median HBV DNA of 4116 pg/ml (2885-6628)]. Group B
      consisted of 33 patients without treatment [18 males, mean age 24.75+/-6.92
      years, median ALT of 30 IU/L (19-39), median HBV DNA of 4094 pg/ml (782-7387)].
      Main outcome measure was sustained virologic response, which was defined as loss
      of HBV DNA in serum with HBeAg seroconversion at least 12 months thereafter.
      Follow-up lasted 12 months after the first dose. RESULTS: No significant effects
      were observed in the treated population in the reduction of HBV DNA to
      undetectable levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels.
      At the end of follow-up, sustained virologic response was almost similar in the
      study as well as control group (7.6% vs. 3.0%, p=0.502). None of the 13 patients
      who received lamivudine therapy had HBeAg seroconversion during the study period.
      In addition, the suppression of serum HBV DNA was temporary; prolonged
      suppression could be achieved in only one patient in the follow-up period. The
      median levels of HBV DNA and ALT values between baseline and month 12 did not
      differ significantly between groups. All patients remained HBsAg positive and
      none developed anti-HBs. The therapy was well tolerated and post-therapy flare
      was not observed in any patient after stopping lamivudine therapy. CONCLUSIONS: A
      short course of lamivudine therapy resulted mostly in only temporarily depressed
      serum HBV DNA levels without significant change in viral clearance. Whether
      permanent suppression of HBV DNA can be achieved in this special population of
      HBsAg carriers by long-term treatment with lamivudine awaits further controlled
      trials. New and safe modalities of therapy are needed for the satisfactory
      treatment of these asymptomatic but viremic patients.

PMID- 15264117
TI  - The mutations in ISDR of NS5A gene are not associated with response to interferon
      treatment in Turkish patients with chronic hepatitis C virus genotype 1b
      infection.
AB  - BACKGROUND/AIMS: A significant association between variations in amino acid
      sequences resides between 2209-2248 nucleotides of HCV non-structural 5A (NS5A)
      gene, and response to interferon treatment has been proposed. The aim of this
      study was to determine whether the amino acid sequence changes in ISDR could be
      correlated to response to alpha interferon treatment in Turkish patients infected
      with HCV genotypes 1b and 1a. METHODS: Thirty-nine patients with chronic C virus
      infection (35 and 4 patients with genotype 1b and 1a, respectively), receiving
      3x3-5 MU of interferon a-2b for six months were included in the study. Following
      PCR amplification of the region from pre-treatment serum samples, the products
      were directly sequenced. The amino acid sequence of NS5A was compared with the
      published sequence for HCV-J (AA 2209-2248). Mutant type was defined as three or
      more amino acid mutations, and intermediate type as 1-3 amino acids in this
      region. Otherwise, they were defined as the wild type (no amino acid mutations).
      HCV RNA serum viremia levels were analyzed by branched DNA assay. RESULTS:
      Eighteen patients were responders (R; 46%), whereas 21 patients were non
      responders (NR; 54%). Amino acid changes in both R and NR groups did not show
      significant difference. Intermediate or wild type strains were detected in both
      groups. CONCLUSIONS: In this study, we could not determine a significant
      association between number of amino acid changes in NS5A2209-2248 and response to
      interferon treatment. In the majority of the patients, it seems that amino acid
      sequences in this region are well conserved.

PMID- 15264118
TI  - Esophageal variceal ligation for acute variceal bleeding: results of three years'
      follow-up.
AB  - BACKGROUND/AIMS: Endoscopic variceal ligation is widely accepted as the optimum
      endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding
      course and long-term outcome of patients with esophageal variceal hemorrhage
      after ligation have been poorly defined. Therefore, we conducted a long-term
      follow-up study to delineate the outcome of ligation. METHODS: Twenty-one liver
      cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were
      treated by endoscopic variceal ligation. These patients received regular follow
      up and detailed clinical assessment of at least 24 months. RESULTS: Twenty-one
      eligible patients were followed up for a mean of 44.45 months (range 33.5-64
      months). The mean number of sessions required to obtain eradication was 3.57+/
      1.99 (range 1-8). Esophageal varices could be obliterated within 11.57+/-6.8
      weeks (range 3-30). The percentage of variceal recurrence during follow-up was
      57.14% (12/21) after endoscopic variceal ligation. Recurrence were observed in a
      mean of 34 months (median 29 months). Rebleeding from esophageal varices appeared
      in four patients (19.04%). The appearance rates of portal hypertensive
      gastropathy and fundal gastric varices after varice obliteration were found to be
      45.45% (5/11) and 25% (3/12), respectively. CONCLUSIONS: Based on the results of
      long-term follow-up of endoscopic variceal ligation, although the percentage of
      variceal recurrence was high, endoscopic ligation achieved variceal obliteration
      faster and in fewer treatment sessions. Furthermore, endoscopic variceal ligation
      had a lower rate of rebleeding and of development of fundal gastric varices, but
      high portal hypertensive gastropathy.

PMID- 15264119
TI  - Comparison of cefotaxime and ofloxacin in treatment of spontaneous bacterial
      peritonitis.
AB  - BACKGROUND/AIMS: Gold-standard treatment of spontaneous bacterial peritonitis
      currently involves 3rd generation cephalosporins. To evaluate the efficacy of
      ofloxacin in this infection, we compared a combined therapy with intravenous and
      oral ofloxacin to intravenous cefotaxime. METHODS: Thirty cirrhotic patients with
      spontaneous bacterial peritonitis were assigned to receive either intravenous (1
      g/12 h) cefotaxime for 7 days (n=17) or intravenous (200 mg/12 h) ofloxacin for 2
      days followed by oral (200 mg/12 h) ofloxacin for 5 days (n=13). All cases had
      community-acquired spontaneous bacterial peritonitis. RESULTS: The infection
      resolution rate on the 7th day of therapy was 82.4% in the cefotaxime group and
      92.3% in the ofloxacin group. Hospital survival rates were 82.4% and 100%,
      respectively. CONCLUSIONS: Oral ofloxacin after a short course of intravenous
      ofloxacin is effective in the treatment of uncomplicated spontaneous bacterial
      peritonitis. This regimen may allow physicians to treat these patients as
      outpatients as soon as their intravenous therapy is completed.

PMID- 15264121
TI  - Liver abscess as a rare complication of Crohn's disease: a case report.
AB  - Pyogenic liver abscess is a rarely seen extraintestinal complication of Crohn's
      disease. It has different features from other liver abscesses. Its clinical and
      laboratory findings are not specific and mimic the reactivation of Crohn's
      disease and diagnosis can be delayed. The radiological methods are very useful in
      diagnosis and treatment of liver abscess. In this paper, we present a patient
      with pyogenic liver abscess which developed in the course of Crohn's disease.

PMID- 15264120
TI  - Should sentinel lymph node mapping be performed for colorectal cancer?
AB  - BACKGROUND/AIMS: Correct determination of lymphatic nodal statement is essential
      to stage correctly and to predict survival. As it is vital to make an assessment
      about the adjacent lymph node(s), this study was designed to compose a sensitive
      detection on the sentinel lymph nodes (SLN) indicating tumoral lymphatic basin
      using advanced pathologic examination. MATERIALS AND METHODS: From June 2002 to
      June 2003, this prospective study was performed in 41 patients undergoing
      standard resection for colorectal cancer. In this study we employed the ex-vivo
      SLN mapping technique. RESULTS: At least one SLN in 37 of 41 patients was
      identified (90.2%). The lymph nodes (LN) from those patients were studied by
      hematoxylin and eosin dye (H&E) and multisectioning. Twenty of 37 patients with
      trace of the metastasis were found. The remaining 17 patients without any
      metastatic LN by H&E underwent clarification of micrometastases (MM) using
      immunohistochemical (IHC) staining technique. Two patients (11.7%) had MM in the
      SLN(s). Upstaging was evaluated in those two. The sensitivity of SLNs was
      obtained as 90%. Two patients with no metastatic SLN had metastasis in the non
      sentinel LNs. CONCLUSIONS: In the LNs from the basin of tumor, MM exposed by IHC
      staining was still not obvious to indicate poor prognosis. The need for treatment
      adjustment in those patients is clear since the upstaging was evident.

PMID- 15264122
TI  - Dydrogesterone-induced hepatitis and autoimmune hemolytic anemia.
AB  - Dydrogesterone, similar to women's natural progesterone, has been used in a wide
      range of gynecological conditions. Despite its widespread use, dydrogesterone
      induced hepatotoxicity and dydrogesterone-induced hemolytic anemia have, to the
      best of our knowledge, never been reported previously. We describe a case of
      hepatitis and warm antibody hemolytic anemia due to dydrogesterone.

PMID- 15264123
TI  - Paraneoplastic cholestasis associated with prostate carcinoma.
AB  - Paraneoplastic syndromes associated with prostate carcinoma are very rare. We
      report a patient with prostate carcinoma and cholestatic jaundice without biliary
      obstruction, hepatic involvement or infectious etiology. In the literature, only
      one case of idiopathic cholestatic jaundice with prostate carcinoma has been
      reported and a paraneoplastic etiology was suggested. In our case, cholestasis
      rapidly regressed with chemotherapy and the patient is well at six months of
      follow-up. Paraneoplastic cholestasis should be kept in mind in the absence of
      biliary tract obstruction, hepatic involvement or infectious etiology.

PMID- 15264124
TI  - Acute pancreatitis possibly due to arginine use: a case report.
AB  - Arginine has been used by millions of athletes over the past 20 years to enhance
      production of human growth hormone. The effects of arginine supplementation
      include increased fat burning and muscle building, enhanced immunity, and
      improvement in erectile function in men. Excessive doses of basic amino acids
      such as ethionine, methionine and lysine are known to damage the rat pancreas.
      Recent studies have demonstrated that excessive doses of arginine induce
      necrotizing pancreatitis in rats. In this article, we report a 16-year-old male
      patient hospitalized in our clinic because of severe pain in upper abdomen,
      nausea and vomiting who was suspected to have arginine-induced acute
      pancreatitis.

PMID- 15264125
TI  - Inflammatory fibroid polyp of the ileum causing intussusception: a case report.
AB  - Inflammatory fibroid polyp is a rare polypoid lesion of the gastrointestinal
      tract, histologically characterized by an admixture of numerous small blood
      vessels, fibroblasts and edematous connective tissue, accompanying a marked
      inflammatory cell infiltrate which contains eosinophils. Although it generally
      presents as a polypoid mass in the gastric antrum, it can be seen throughout the
      gastrointestinal tract. It is believed to represent a reactive, nonneoplastic
      condition, but its histogenesis remains controversial. A case of inflammatory
      fibroid polyp of the ileum presenting clinically as intestinal obstruction due to
      intussusception is presented here.

PMID- 15264126
TI  - Spontaneous bacterial empyema in cirrhosis.

PMID- 15264127
TI  - Abdominal gossypiboma: ultrasonography and computerized tomography findings.

PMID- 15264135
TI  - [Therapy options in lower kidney calix calculus].

PMID- 15264137
TI  - [Personal surgical tips and tricks].

PMID- 15264138
TI  - [How do I do bougienage and secure the ureter in ureterorenoscopy?].

PMID- 15264140
TI  - [Introduction of practice fees].

PMID- 15264141
TI  - [Questions for the specialist physician. Bellini's duct carcinoma].

PMID- 15264142
TI  - [Questions for the specialist physician. Sarcomatoid carcinoma and
      carcinosarcoma].

PMID- 15264143
TI  - [Guideline use by physicians -- how is it possible?].

PMID- 15264156
TI  - [Immunological disorders in epileptic patients are associated to the
      epileptogenic focus localization].
AB  - OBJECTIVE: Clinical and experimental data support the role of immune mechanisms
      in the pathogeny of epilepsy. The purpose of this work was to study the
      immunological aspects in 30 epileptic patients with complex partial crisis
      resistant to antiepileptic drugs. PATIENTS AND METHODS: The patients were
      evaluated by EEG-Video and they were grouped attending to epileptogenic focus
      localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n =
      4). We also studied a group with psychogenic epilepsy (n = 4), this group was
      diagnosed after EEG-video evaluation. The following immunological evaluations has
      been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial
      immunodiffusion test and lymphocytic subpopulations using immunocytochemical
      methods. We measured the percent of T and B lymphocytes (CD3 and CD20),
      helper/inductor lymphocyte T (CD4), suppressor/cytotoxic (CD8), interleukine-2
      receptor (CD25) and human leukocyte antigen (HLA-DR). RESULTS: The results show a
      significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers
      (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to
      different group of epileptogenic focus localization shown that the increase of
      CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The
      patients with extratemporal localization of focus and the psychogenic cases shown
      normal values for the evaluated immunological lymphocyte markers. We did not find
      a deficit in the humoral immunological aspects. CONCLUSIONS: Taking into account
      that patients diagnosed as psychogenic received an antiepileptic drug treatment
      identical to that of the other group, the observed immunological changes might be
      related with the patogeny of certain epilepsy variants associated with the focus
      localization and not with the medication.

PMID- 15264157
TI  - [A study of evoked potentials in the brains of very low birth weight infants].
AB  - INTRODUCTION: This work studies the behaviour of the N200 and P300 waves of the
      brain evoked potentials (BEP) in a group of very low birth weight infants and
      results are compared with a second group of children whose weight was normal at
      birth. AIMS: The objective of this study was to determine whether the N200 and,
      more especially, the P300 waves in children under the age of 3 could be used to
      assess the development and prognosis of their disorders. PATIENTS AND METHODS:
      BEP were performed in very low birth weight infants (taken as the test group) and
      in others whose weight at birth was normal (control group); the difference in
      ages when the potentials were recorded was not statistically significant.
      RESULTS: The EEG index was evaluated for both the test and the control group, and
      a difference was found with a significance of p < 0.001. Latency, in
      milliseconds, of the N200 wave and the P300 wave was recorded at the same sites
      for the test and control groups and showed differences with a significance of p <
      0.001. CONCLUSIONS: The findings from the EEG and the latencies of the N200 and
      P300 waves in the BEP of very low birth weight infants are pathological and are
      linked to immaturity of the brain, which is characteristic of this population.
      This tool could help to detect developmental disorders and to facilitate a better
      approach to attending these children.

PMID- 15264158
TI  - [Gender-specific post-stimulus modulation in the alpha band during visual-spatial
      attention].
AB  - INTRODUCTION: Previous studies of the spontaneous activity of the EEG indicate
      that women present bigger absolute spectral power in the alpha band than men, but
      few studies have been done during cognitive activity. AIM: To check possible
      gender differences in the EEG frequency domain during a visuo-spatial attentional
      task to understand better the temporary dynamics of alpha. SUBJECTS AND METHODS:
      A classic oddball paradigm was used whose stimuli (90% standard-10% objectives)
      were complex. In each block (10 with 100 trials) it was requested to the subjects
      (20, 10 of each gender) to attend to one of the visual fields (left and right,
      with random stimuli and identical probability). Power spectral density values
      were calculated applying the fast Fourier transform in the alpha band (9-11 Hz)
      in two overlapped windows (sliding windows): of 0-512 ms and of 412-924 ms.
      RESULTS: The normalized data were analyzed by means of ANOVAs, with the following
      factors: gender, attention, hemisphere, visual field and electrodes. CONCLUSIONS:
      Different modulations were obtained attending to the gender variable: men showed
      smaller alpha or bigger suppression of the rhythm in posterior electrodes and
      women exhibited smaller power in anterior electrodes.

PMID- 15264159
TI  - [A survey of sleeping difficulties in an urban Latin American population].
AB  - AIMS: To report the results of the first regional survey on the prevalence of
      sleep disturbances in an urban Latin American population. SUBJECTS AND METHODS:
      Door-to-door and telephone interviews in main urban areas were performed in two
      phases. In phase one, 1776 adults, aged 18 to 70 were interviewed in Buenos Aires
      and Sao Paulo. In phase two, adults aged 18 to 77 were interviewed in Buenos
      Aires, Sao Paulo and Mexico City (n = 300 in each city). RESULTS: Two-thirds of
      those surveyed in phase 1, regardless of age and gender, reported some type of
      sleep problem within the last 12 months. Up to 25 % of individuals surveyed in
      phase 2 reported being severely affected or moderately affected by their sleep
      problems. The severity of the condition increased with age, women being more
      severely affected than men. On average, individuals reported suffering from sleep
      difficulties for a period of 5 years and were affected 15.5 nights per month.
      Although 8.2 hours of sleep was most desired, Latin Americans were sleeping on
      average 5.8 hours per night. Those severely affected lost about 3 hours per
      night. Individuals reported stress and worry as the primary trigger for their
      sleep problems, followed by health concerns. All respondents reported the
      negative impact of poor sleep on their health and quality of life. CONCLUSIONS:
      The survey indicates that the prevalence of sleep difficulties in an urban Latin
      America population is high.

PMID- 15264160
TI  - [An analysis of the health care activity of on-call neurologists and its
      repercussions in the hospital].
AB  - INTRODUCTION: The implementation of an on-call neurology service at our hospital
      prompted us to analyse the health care it offers. PATIENTS AND METHODS: We
      conducted a retrospective descriptive study by reviewing the status report of the
      on-call services performed between 15 April 2002 and 14 April 2003. The data
      collected included the age, sex, day of the week, month, requesting service,
      destination and pathology grouped under different codes to facilitate their later
      analysis. RESULTS: A total of 1910 patients were attended with a mean age of 53
      and with no differences between sexes. The service that most often requested
      evaluation was casualty with over 80% of cases. The most frequently involved
      pathologies were headaches (19.7%), followed by ischemic strokes (16.1%) and
      epilepsy (13.4%). In 12.3% of cases no neurological pathology was observed. The
      percentage of direct hospital discharges was 29.16%, while that of admissions to
      neurology was lower (23.56%). Patients requiring further follow-up visits to
      Neurology were remitted normally (12.56%), compared to those who were in need of
      preferential treatment (4.45%). CONCLUSIONS: The need for a duty neurologist has
      provided our hospital with a better evaluation of neurological pathologies and a
      more rational use of complementary tests. Many of the patients who were evaluated
      were given a direct hospital discharge. This has led to a drop in the number of
      admissions to Neurology by almost 30% and a reduction in the mean length of time
      spent in hospital.

PMID- 15264161
TI  - [Hypothalamic-infundibular histiocytosis: magnetic resonance findings].
AB  - INTRODUCTION: We report the magnetic resonance imaging (MRI) of a case of
      Langerhans cell histiocytosis in the pituitary. Isolated central nervous system
      involvement is uncommon. CASE REPORT: An eighteen-years old female patient who
      had an acute onset of central diabetes insipidus because of the Langerhans cell
      histiocytosis. The MRI evidenced a lesion in the hypothalamic-pituitary axis. The
      hyperintensity in the posterior pituitary lobe, which is seen in normal subjects
      on T1-weighted images, was absent. The pituitary stalk was thickened and enhanced
      homogeneously following contrast administration. During the follow-up, the
      infundibullar lesion extended to the hypothalamic region and other systemic
      manifestations appeared. Diagnosis of Langerhans cell histiocytosis was confirmed
      by lung biopsy. After radiotherapy and chemotherapy, MRI showed regression of the
      hypothalamic-pituitary lesion. CONCLUSION: The combination of these findings,
      although nonspecific of Langerhans cell histiocytosis, should nevertheless prompt
      further studies, including chest films, bone scanning and temporal bone
      computerized tomography in order to narrow the differential diagnosis.

PMID- 15264162
TI  - [Is benign childhood paroxysmal eye deviation a non-epileptic disorder?].
AB  - INTRODUCTION: Benign childhood paroxysmal eye deviation (BCPED) is classified as
      a 'non-epileptic paroxysmal disorder'. CASE REPORTS: We report the cases of four
      patients aged between 6 months and 2 years, who suffered brief episodes of upward
      conjugate gaze deviation, with no clonic movements or associated cognitive
      deterioration. These episodes, which lasted several seconds, appeared in short
      repeated bouts that became worse with fatigue. Results of the neurological
      exploration, laboratory examinations, neuroimaging (CAT, MRI, brain
      ultrasonography) and a neurophysiological study, which included EEG-video
      monitoring and EEG performed during the waking state, were all normal. A
      nocturnal polysomnographic study was later conducted for 7-8 hours and EEG, EMG
      and EOG readings were recorded. The trace showed focal or generalised paroxysmal
      discharges during non-REM sleep in the form of polyspike-wave and spike-wave
      complexes. Sleep analysis (Reschstaffen and Kales) showed only a shortened REM
      sleep latency, with no clear clinical meaning. Several cases have been reported
      in the literature with identical symptoms and normal results in the diagnostic
      tests, including daytime polysomnography. CONCLUSIONS: The appearance of these
      epileptic anomalies in the nocturnal study makes it necessary to perform a
      complete nocturnal polysomnography. In spite of these findings, BCPED courses
      favourably and has a benign prognosis both with and without antiepileptic
      treatment. We therefore believe that BCPED should be classed within the group of
      'benign idiopathic epilepsies of childhood'.

PMID- 15264163
TI  - [West syndrome as an epileptic presentation in Menkes' disease. Two cases
      report].
AB  - INTRODUCTION: Menkes' disease is a neurodegenerative disorder, recessive X
      chromosome linked (Xp13.3) that normally codify an ATPasa copper transporter.
      CASE REPORTS: Case 1: patient exhibit failure in the gastrointestinal copper
      absorption, which is insufficient to cover the needing during the first twelve
      months of life. The first case was a 5 months male. His developmental skills were
      normal until he was 5 months old, when he exhibited visual impairment and failure
      to continue getting normal developmental skills. One month later he had infantile
      spasms and hypsarrhythmia in the EEG. He had kinky hair, alopecia zones and
      copper serum level in 0 microg/dL (range 590-1,180 microg/dL) brain CT scan
      revealed diffuse cortical atrophy. The patient is 5 years old now, he is free of
      seizures but he has a severe neurological impairment. Case 2: he is a 7 months
      old male who developed during the two days of life hypotonia and weak suction. He
      exhibited later hypertonia, delayed neurological development and infantile
      spasms, microcephaly, kinky hair, blindness and EEG pattern of hypsarrhythmia.
      The serum copper level was 84 microg/dL (range: 590-1,180 microg/dL). The brain
      CT scan showed generalized atrophy, including cerebellum, extradural effusion and
      MRI with multiple infarcts in different stages. Electronic microscopy revealed
      pili torti. In both cases the diagnosis was suspected because of the hair and
      eyebrow features. CONCLUSIONS: We suggest a careful hair and eyebrow clinical
      exam in those patients with delayed milestones and early epilepsy without a
      documented etiology, and the copper serum level determination in those patients
      with suspected disease.

PMID- 15264164
TI  - [Myelopathy due to Schistosoma mansoni. A description of two cases and review of
      the literature].
AB  - INTRODUCTION: Schistosomiasis is a parasitic infection caused by Schistosoma sp
      that affects over 200 million people worldwide. The neurological manifestations,
      caused by the eggs or by anomalous migration of the parasite, can be epileptic
      seizures and myeloradicular syndromes. S. mansoni is endemic in Brazil and is an
      underdiagnosed cause of transverse myelitis and myeloradiculopathy. CASE REPORTS:
      We present the cases of two Brazilian women, aged 28 and 32, who suffered from
      conus medullaris and cauda equina syndrome, and a thoracolumbar myelopathy,
      respectively. Diagnosis was based on the epidemiological exposure, suggestive
      neurological syndrome and positive serological studies in blood or cerebrospinal
      fluid (CSF) by means of indirect immunofluorescence (IFI) for S. mansoni. Other
      causes of myeloradiculopathy were dismissed. The first patient presented
      progressive sphincteric, motor and dysesthetic symptoms that suggested cauda
      equina and conus medullaris syndrome. Examination of the CSF revealed
      pleocytosis, eosinophils and high protein levels; (IgG) IFI was positive for S.
      mansoni. Spinal cord magnetic resonance imaging showed an increased volume in the
      conus and epiconus, areas of hypersignal in T2 and heterogeneous contrast
      enhancement. Case 2 presented an acute picture of paresthesias and myoclonias in
      the lower limbs. Serological analysis for S. mansoni in blood was positive. S.
      mansoni eggs were found in faeces. Results of the CSF study were normal. Both
      patients were treated with praziquantel and prednisone and responded well both
      clinically and radiologically. CONCLUSIONS: In patients with epidemiological
      evidence of exposure to S. mansoni, lumbosacral myeloradiculopathy is suggestive
      of neuroschistosomiasis.

PMID- 15264165
TI  - [Coexistence of syringomyelia and extramedullary intradural meningioma].
AB  - INTRODUCTION: The coexistence of non-communicating syringomyelia with
      extramedullary intradural tumours in surgical series is extremely rare. CASE
      REPORT: We report the case of a 68-year-old female who had been suffering from
      predominantly proximal asymmetrical progressive paraparesis, with no involvement
      of the sphincters; the clinical exploration revealed a band of thermal
      hypaesthesia D7-D8. Magnetic resonance imaging (MRI), following the
      administration of gadolinium, confirmed the coexistence of an extramedullary
      intradural expansive lesion, which had features suggesting it could be a
      meningioma, and a dorsal syringomyelia. The cavity involved two medullary
      segments situated above the tumour and there were no associated anomalies at the
      junction of the medulla and upper spinal cord. Following complete resection of
      the tumour, which was diagnosed histologically as being a transitional meningioma
      with abundant psammoma bodies, the patient recovered the ability to walk
      independently. CONCLUSIONS: MRI with contrast is the best diagnostic means
      available for the detection and delimitation of the two components in this rare
      association, although its capacity to detect signs suggesting turbulences in the
      intracavity fluid, especially in small cavities, has still to be confirmed. The
      variations in the size and situation of the cavity with respect to the seat of
      the tumour, and the fact that progress is seldom monitored with MRI in the cases
      published to date, do not allow us to identify the pathogenic mechanism
      responsible for this association or to suggest the best type of shunt to prevent
      a possible expansion of the syringomyelic cavity.

PMID- 15264166
TI  - [Protocortex versus protomap: a perspective from the olfactory bulb].
AB  - INTRODUCTION AND AIM: The olfactory sensory system is a unique model for the
      research of guidance and connectivity of growing axons. During development, the
      olfactory epithelium, the olfactory bulb and the olfactory cortex differentiate
      several cell types and extend projection axons. Because there is a close
      relationship between these three structures, we ask the question as to whether
      establishment of the olfactory bulb central projections can proceed independently
      of the arrival of the olfactory sensory afferents. This raises another more
      general question: is establishment of afferent connections necessary to awake a
      developmental program in target cells?. DEVELOPMENT: The initial establishment of
      the olfactory bulb central projections occurs independently of the arrival of the
      olfactory axons from the olfactory epithelium, which reinforces the idea that
      cortical regions are already patterned before migration of newborn neurons, at
      least for the olfactory bulb and maybe for the entire brain. This implies a
      strict intrinsic molecular control of the distinct olfactory structures,
      independent one of each other. CONCLUSIONS: How then, do axonal projections find
      their correct way within the brain? Contact-mediated mechanisms and chemotropic
      molecules cooperate to fix their position in the telencephalon, prevent bulbar
      axons from invading structures other than the olfactory cortex and, at the same
      time, stimulate axonal branching in an orchestra of both, attractive/promoting
      and repulsive/inhibiting signals. At later stages, the mature appearance of the
      olfactory bulb will be completed and refined.

PMID- 15264167
TI  - [Pathophysiology of focal cerebral ischemia: fundamental aspects and its
      projection on clinical practice].
AB  - AIM: The aim of this study is to review the basic aspects of focal cerebral
      ischemia as a fundamental element in clinical practice and of neuroprotective
      strategies. DEVELOPMENT: Ischemia triggers several different responses in nerve
      tissue which, according to the degree of energetic limitation, can be adaptive or
      lead to cell death due to necrosis or apoptosis. Establishing these processes is
      a complex task and the mechanisms involved have still not been fully explained;
      this is made more difficult by the fact that many of them are simultaneous and
      also because of the implications they may have, not only in cell death but also
      in the adaptation of the neurons that suffered ischemic stress and survived. We
      outline the foundations for understanding the physiopathological phenomena at
      work in ischemia: neuronal stress and death, and the reaction of the macroglial
      and microglial cells. This is also illustrated by original images from research
      into cell response to ischemia at a pre-clinical level in an experimental model
      of focal cerebral ischemia in rats, evaluated using, for example, hematoxylin
      eosin and immunohistochemical techniques for several cell markers. CONCLUSIONS:
      Cell death in ischemia is a complex phenomenon that can have two different
      outcomes: necrotic death or apoptotic death. Basic knowledge of the
      pathophysiology of ischemia and of the response of microglial and macroglial
      cells is the foundation for elaborating neuroprotective-type strategies, which
      must not only be oriented towards preventing acute cell death, but also later
      modes of cell death or strengthening the surviving tissue.

PMID- 15264169
TI  - [Cognitive functions of the frontal lobe].
AB  - INTRODUCTION AND DEVELOPMENT: One way to divide the different regions of the
      frontal lobe is according to its connections with the thalamic regions. Each of
      these regions, with their own particular cytoarchitecture, phylogeny and
      ontogeny, are also involved in distinct cognitive functions. The dorsolateral
      prefrontal cortex enables plans of action to be developed and executed, and
      working memory, which is needed for most cognitive processing, is the driving
      force behind what we call the executive functions. The orbital cortex and its
      subcortical connections make up a circuit that allows attention to be held and
      directed through a series of inhibitory mechanisms; this in turn prevents
      interference by stimuli that are irrelevant for a particular purpose. Finally,
      the cingulate cortex plays a part in initiating actions, in the intentionality of
      responses and in focusing attention. CONCLUSIONS: A deeper knowledge of the
      mechanisms behind the workings of the frontal lobe can explain the clinical
      pictures that are observed in many of the pathologies that appear during infancy,
      such as attention deficit hyperactivity disorder.

PMID- 15264168
TI  - [Neuropsychology and epilepsy].
AB  - AIMS: The epileptic child has three times more risk of presenting cognitive
      disorders than other children with no neurological pathology, in accordance with
      three essential facts: 1. The effect exerted by the actual epilepsy. 2. Any
      associated previously-existing neuropsychosocial deficits. 3. The side effects of
      the antiepileptic drug (AED). A certain amount of deterioration is universally
      accepted, without defining the factors involved in its production, but which are
      multifactorial according to computer studies. From this point of view, we analyse
      the relation between neuropsychology and epilepsy in Paediatrics. DEVELOPMENT:
      The relation between epilepsy and behaviour must be seen as an exception and not
      the rule, unless there are coexisting personality disorders and/or mental
      deficiency. The cognitive effects of AED depend on the drug, the doses used and
      on the polypharmacy, and these effects may be both adverse and beneficial. The
      differences from one drug to another are questionable due to the methodology used
      in the different studies and it should be remembered that with suitable doses the
      side effects are generally moderate, and AED monitoring is useful in this case.
      We recommend the use of MEDDRA assessment to obtain a more reliable definition of
      side effects, which in turn will allow them to be better evaluated. Scaling time
      in the introduction of the drug is important, especially with some of the new
      AED. The mechanisms governing the production of the side effects vary, but both
      the classical and the new ones, which are well used owing to the greater
      knowledge we have of their mechanism of action, improve cognitive functioning by
      controlling the seizures. In infancy, idiopathic cognitive reactions are
      produced. In childhood, the main disorders are a diminished reaction and
      information processing time with alterations affecting memory, attention and
      language. CONCLUSIONS: Epilepsy is associated to a number of different, generally
      mild, cognitive problems. The age of onset of epilepsy, type of syndrome, its
      aetiology, the response to treatment and polypharmacy are multifactorial elements
      conditioning side effects. There is a need for batteries of tests capable of
      forecasting the future and controlling the progression of cognition during
      therapy. It can be concluded that the side effects of AED affecting cognition and
      behaviour are generally mild, but the cognitive side effect of an AED can be
      important for a particular child.

PMID- 15264170
TI  - [Magnetoencephalography in cognitive disorders involving frontal lobes].
AB  - INTRODUCTION AND DEVELOPMENT: Frontal lobe, more specifically prefrontal cortex,
      is one of the brain regions that undergoes more protracted ongoing development.
      The wider the developmental window of one brain structure, the more vulnerable
      the functions related to it. Hence, executive functions, which are mediated by
      prefrontal networks, seems to be specially vulnerable during childhood. Attention
      deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      neurodevelopmental disorders. Functional neuroimaging techniques have shown a
      dysfunction in a fronto-striatal network in this disorder, that is likely
      subserving deficits in executive processes, such as in response inhibition.
      DISCUSSION: This review focuses on contributions of neuroimaging techniques, with
      high spatial (SPECT, PET and fMRI), temporal (ERP) and spatio-temporal (MEG)
      resolution, to the neurofunctionality of ADHD.

PMID- 15264171
TI  - [Executive system and frontal lobe lesions in childhood].
AB  - INTRODUCTION AND DEVELOPMENT: Frontal lobe syndrome in adulthood is characterised
      by executive function deficits leading to altered behavioural control with
      difficulties in social interactions and in maintaining stable jobs and
      interpersonal relationships. Generalisation of this concept to children with
      early frontal lobe damage is not straightforward. There are complex interactions
      between the effects of the lesion itself and the effects in other interconnected
      regions, timing of lesion, how long it was since the lesion occurred to the time
      of evaluation, and how old the child is at examination. These facts lead to
      consider that there might be a number of 'frontal syndromes' in childhood rather
      than a unique one. We report 9 cases of children with early frontal lobe lesions
      who were followed up for an average of 10 years. CONCLUSION: A variety of
      different outcomes suggests that prognosis for these patients might be better
      that previously reported.

PMID- 15264172
TI  - [Attention deficit hyperactivity disorder and epilepsy].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is currently one of
      the morbid clinical pictures in childhood and adolescence that is most frequently
      diagnosed in the Neuropaediatric clinic. DEVELOPMENT: ADHD is sometimes
      associated to other important neurological problems, such as behavioural
      disorders, tics or headaches, and may occasionally be related to epilepsy,
      although in this particular case the epileptic syndromes often involve disorders
      affecting behaviour and attention. Due to the frequent association of these
      disorders (epilepsy and ADHD) it is wise to perform an electroencephalographic
      study in patients who visit because of symptoms of disattention. Likewise, the
      neuropsychological assessment of epileptic children must not be neglected. We
      analyse the therapeutic options regarding the use of stimulants when both
      disorders coexist and we endorse the association of antiepileptic and
      psychostimulant drugs when necessary.

PMID- 15264174
TI  - [Arterial hypertension as a risk factor for hemifacial spasm due to vascular
      compression].

PMID- 15264175
TI  - [Basilar artery thrombosis: recanalisation following intravenous administration
      of heparin demonstrated by magnetic resonance angiography].

PMID- 15264176
TI  - Awareness of kidney disease in the US population: findings from the National
      Health and Nutrition Examination Survey (NHANES) 1999 to 2000.
AB  - BACKGROUND: The prevalence of end-stage renal disease (ESRD) in the US population
      has been predicted to increase by 48% during the next decade and will pose a
      significant health cost burden. Early identification and treatment of chronic
      kidney disease (CKD) is necessary to delay progression from CKD to ESRD. CKD
      awareness among patients is crucial to early intervention programs, but its
      prevalence and characteristics in the noninstitutionalized US population are
      unknown. METHODS: The National Health and Nutrition Examination Survey 1999 to
      2000 was used to determine prevalence estimates of kidney disease awareness, as
      well as demographics, health care access, and comorbid characteristics, of
      participants with CKD. RESULTS: In participants with CKD, 40.5% of patients with
      stage 1, 29.3% of patients with stage 2, 22.0% of patients with stage 3, and
      44.5% of patients with stage 4 CKD were aware of their kidney disease,
      respectively. The aware and unaware groups did not differ by health care access.
      In multivariate regression modeling, lack of awareness was significantly
      associated with sex, race-ethnicity distribution, and hypertension. CONCLUSION:
      Kidney disease awareness is low among a representative sample of the
      noninstitutionalized US population. Groups at greater risk for kidney disease,
      such as non-Hispanic blacks, patients with hypertension, and men, were more
      likely to be unaware of having kidney disease, even with health care access
      similar to that of the aware group. Increased efforts to promote kidney disease
      awareness are needed and probably should target primary care providers involved
      in the screening process.

PMID- 15264177
TI  - Kidney disease as a risk factor for recurrent cardiovascular disease and
      mortality.
AB  - BACKGROUND: Chronic kidney disease (CKD) is highly prevalent in the United States
      and is an independent risk factor for adverse cardiovascular disease (CVD) and
      all-cause mortality outcomes in patients with acute coronary syndromes. Few
      studies have evaluated the effect of CKD on cardiovascular events in a diverse
      community-based population with underlying CVD. METHODS: Data for subjects with
      preexisting CVD were pooled from 4 publicly available, community-based,
      longitudinal studies: Atherosclerosis Risk in Communities, Cardiovascular Health
      Study, Framingham Heart Study, and Framingham Offspring Study. CKD was defined as
      an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (<1 mL/s/1.73
      m2). The primary study outcome was a composite of myocardial infarction (MI),
      fatal coronary heart disease (CHD), stroke, and all-cause mortality. The
      secondary outcome included only MI and fatal CHD. RESULTS: A total of 4,278
      subjects satisfied inclusion criteria, and 759 subjects (17.7%) had CKD. Mean
      follow-up was 86 months. The primary and secondary outcomes were observed in
      1,703 (39.8%) and 857 subjects (20.0%), respectively. Incidence rates for the
      primary and secondary outcomes were greater in persons with CKD compared with
      those without CKD (62.5% versus 34.9% and 30.6% versus 17.8%, respectively).
      Adjusted hazard ratios for the primary and secondary outcomes were 1.35 (95%
      confidence interval [CI], 1.21 to 1.52) and 1.32 (95% CI, 1.12 to 1.55),
      respectively. CONCLUSION: The presence of CKD in a community-based population
      with preexisting CVD is associated with an increased risk for recurrent CVD
      outcomes. This increased risk persists after adjustment for traditional CVD risk
      factors.

PMID- 15264178
TI  - The association between depression and chronic kidney disease and mortality among
      patients hospitalized with congestive heart failure.
AB  - BACKGROUND: The point prevalence of depression and its relationship to poor
      outcomes among patients with chronic kidney disease (CKD) has not been fully
      characterized. METHODS: We performed a secondary analysis of a prospective cohort
      of 374 patients admitted with congestive heart failure between March 1, 1997 and
      June 30, 1998, to investigate the point prevalence of depression among patients
      with CKD and its association with mortality. The Beck Depression Inventory (BDI)
      was administered to all patients. Those who scored 10 or higher were administered
      the National Institute of Mental Health Diagnostic Interview Schedule (DIS).
      Logistic regression was used to examine the association between severe CKD,
      corresponding to a creatinine clearance less than 30 mL/min/72 kg (<0.50 mL/s/72
      kg), depression, and mortality at 1 year. RESULTS: Point prevalences of
      depressive symptoms by BDI and major depression by DIS were 54.8% and 21.6% if
      severe CKD was present and 32.8% and 13.0% if severe CKD was absent,
      respectively. After controlling for important clinical factors, severe CKD was
      associated with depressive symptoms by BDI (odds ratio, 2.89; 95% confidence
      interval, 1.39 to 5.99). Both depression by DIS and severe CKD were significant
      predictors of mortality. The increased mortality risk associated with depression
      did not decline with decreasing kidney function. CONCLUSION: Depression was more
      prevalent among patients with than without severe CKD and had at least as strong
      an association with mortality as compared with depression in patients with no or
      less severe CKD. The point prevalence of depression decreased when the DIS
      interview was used, perhaps related to the presence of somatic measures on the
      BDI reflecting uremia. Studies assessing the efficacy of antidepressants among
      patients with CKD are needed to determine whether, in addition to treating
      depression, pharmacotherapy impacts mortality.

PMID- 15264179
TI  - Exercise blood pressure, cardiac structure, and diastolic function in young
      normotensive patients with polycystic kidney disease: a prehypertensive state.
AB  - BACKGROUND: Increased left ventricular mass (LVM) and left ventricular
      hypertrophy have been found in early stages of autosomal dominant polycystic
      kidney disease (ADPKD). The mechanisms that lead to an increase in LVM in this
      population are unknown. The aim of this study is to evaluate blood pressure (BP)
      response to exercise and very early alterations in cardiac structure and
      diastolic function in young normotensive patients with ADPKD. METHODS: Color
      Doppler echocardiography and exercise treadmill testing according to the Bruce
      protocol were performed in 18 young normotensive patients with ADPKD and 18
      healthy subjects. RESULTS: LVM index was greater and isovolumic relaxation time
      (IVRT) was longer in patients with ADPKD than controls (93.3 +/- 21.4 versus 77.5
      +/- 18.6 g/m2; P = 0.02; 100 +/- 20.2 versus 80 +/- 9.7 milliseconds; P = 0.001,
      respectively). Exercise capacity in metabolic equivalents was similar in both
      groups. Systolic BP response during exercise and recovery were similar in both
      groups. Diastolic BP decreased during exercise, but the magnitude of decrease was
      lower in patients with ADPKD than controls (P = 0.01). During recovery, patients
      with ADPKD showed a greater sustained diastolic BP than controls (P = 0.02).
      Patients with ADPKD with an exaggerated systolic BP response had a greater LVM
      index than those with a normal response (112.1 +/- 10.4 versus 84 +/- 19.2 g/m2;
      P = 0.001). Multivariate regression analysis showed that exercise systolic BP and
      diastolic BP were independent predictors of LVM index and IVRT, respectively.
      CONCLUSION: Young normotensive patients with ADPKD showed increased LVM index and
      prolonged IVRT, which are related to exercise BP response. Exaggerated diastolic
      BP response during exercise suggests an impaired capacity for exercise-induced
      vasodilatation and may indicate a greater risk for the development of future
      hypertension.

PMID- 15264180
TI  - Possible mechanism for medial smooth muscle cell injury in diabetic nephropathy:
      glycoxidation-mediated local complement activation.
AB  - BACKGROUND: Although recent studies have emphasized the pathogenic role of
      intrarenal muscular arteries in patients with diabetic nephropathy, notice has
      not been taken of their pathological characteristics. We focused on medial smooth
      muscle cell (SMC) injury and the involvement of glycoxidation and complement
      activation. METHODS: Renal samples were obtained at autopsy from patients with
      diabetes mellitus (DM), patients with hypertension without renal involvement (n =
      9), patients with benign nephrosclerosis (n = 7), and age-matched control
      subjects (n = 12). Patients with DM had glomerulosclerosis classified as severe
      (n = 9; DM-sev), moderate (n = 11; DM-mod), and minimal (n = 7). Renal samples
      were immunohistochemically determined. Activation of plasma complement from
      healthy subjects using advanced glycation end products (AGEs) also was performed.
      RESULTS: A marked SMC loss was noted in the media of patients with DM-sev and DM
      mod. A membrane attack complex (MAC) observed in the area with SMC loss
      correlated well with the loss. Considerable carboxymethyllysine (CML), an
      oxidatively modified AGE, was deposited in the area with SMC loss in patients
      with DM-mod and DM-sev. Degrees of MAC deposition, SMC loss, and CML deposition
      were greater in the DM-sev group than the non-DM groups. Another oxidative
      product, acrolein, colocalized with CML. Plasma complements were not activated by
      AGE-modified bovine serum albumin in our in vitro assays, which included a
      complement hemolytic activity assay and determination of complement fragments,
      including C4d, C3bB, iC3b, and MAC. CONCLUSION: It is strongly suggested that
      medial SMC injury in intrarenal arteries is caused by interaction between
      glycoxidation and complement activation and contributes to the progression of
      diabetic nephropathy.

PMID- 15264181
TI  - FB21, a monoclonal antibody that reacts with a sialic-acid-dependent carbohydrate
      epitope, is a marker for glomerular endothelial cell injury.
AB  - BACKGROUND: FB21 is reactive with glomerular endothelial cells and distal tubules
      of the human kidney and is bound to a sialic-acid-dependent cell-surface antigen.
      We evaluated FB21 staining in fetal kidneys and kidneys of children and adults
      with normal kidneys and glomerulonephritis and investigated whether FB21 can be
      used as a marker for endothelial cell injury. METHODS: This study was performed
      on 6 children, 10 adults, and 12 fetuses with normal kidneys and 113 patients
      diagnosed with primary and secondary glomerulonephritis. We evaluated renal
      staining for FB21 in children with normal kidneys and glomerulonephritis and
      measured serum E-selectin concentrations in patients with hemolytic uremic
      syndrome (HUS) and Henoch-Schonlein purpura nephritis (HSPN). RESULTS: (1) FB21
      was reactive with endothelial cells of normal kidneys and detected on the surface
      of endothelial cells by immunoelectron microscopy. (2) FB21 was reactive with
      endothelial cells in kidneys of fetuses older than 32 weeks. (3) Endothelial cell
      FB21 staining scores in the first renal biopsy specimens of patients with HUS and
      HSPN were lower than those in normal kidneys of children and correlated
      negatively with serum E-selectin concentrations. (4) Endothelial cell FB21
      staining of crescentic and sclerotic glomerular lesions in patients with
      immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, and focal
      glomerulosclerosis was weaker than that in normal kidneys. CONCLUSION: These
      results suggest that FB21 can be used as a marker for glomerular endothelial cell
      injury in various types of glomerulonephritis.

PMID- 15264182
TI  - Possible involvement of circulating fibroblast growth factor 23 in the
      development of secondary hyperparathyroidism associated with renal insufficiency.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a recently identified
      polypeptide that promotes renal phosphate excretion and decreases serum 1,25
      dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily
      elevated in patients with end-stage renal failure. METHODS: Blood and urine
      samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years;
      range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were
      determined by means of a sandwich enzyme-linked immunosorbent assay system using
      2 kinds of monoclonal antibodies that does not detect biologically inactive N
      terminal and C-terminal fragments derived from an identified internal cleavage
      site to date. RESULTS: Serum FGF-23 levels increased with the decrease in
      creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH
      levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative
      correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was
      found. The maximum tubular reabsorptive rate of phosphate correlated negatively
      with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily
      urinary phosphate excretion was significantly less in patients with a Ccr less
      than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels
      were significantly greater (P < 0.001). CONCLUSION: Circulating FGF-23 levels
      increase with the decrease in renal function. FGF-23 is a likely candidate to
      lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin
      to decrease 1,25D levels when it loses its hypophosphatemic action because of a
      decreased number of viable nephrons in patients with advanced renal failure. As
      such, FGF-23 may be an important determinant in the regulation of mineral
      metabolism with renal insufficiency.

PMID- 15264183
TI  - Can young adult patients with proteinuric IgA nephropathy perform physical
      exercise?
AB  - BACKGROUND: It is not known whether physical exercise increases daily proteinuria
      in patients with proteinuric nephropathies, thus accelerating progression of the
      renal lesion. This study evaluates the acute effects of physical exercise on
      proteinuria in young adults with immunoglobulin A (IgA) nephropathy. METHODS:
      Changes induced by intense physical exercise on quantitative and qualitative
      proteinuria were evaluated in basal conditions and after 10 days of ramipril
      therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate
      (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria
      before and after the end of a maximal treadmill Bruce test (B-test). The basal
      study also was performed in 10 age- and sex-matched healthy volunteers. RESULTS:
      At rest, GFR averaged 141 +/- 23 mL/min; it increased by 16.3% +/- 3.3% (P <
      0.005) and 7.1% +/- 1.6% at 60 and 120 minutes after the B-test, respectively. At
      rest, GFR-corrected proteinuria averaged protein of 0.76 +/- 0.21 mg/min/100 mL
      GFR; it increased to 1.55 +/- 0.28 mg/min/100 mL GFR after 60 minutes (P < 0.001)
      and declined to 0.60 +/- 0.11 mg/min/100 mL GFR at 120 minutes after the end of
      the B-test. The pattern of urinary proteins remained unchanged, as did
      microhematuria. Daily proteinuria was not different from the basal value on the
      day of the B-test. After ramipril therapy, patients showed a reduction in GFR,
      but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or
      hematuria. CONCLUSION: The increase in proteinuria after exercise in our patients
      is significant and is not prevented by ramipril therapy, but lasts less than 120
      minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not
      support the need to reduce acute physical activity in patients with nonnephrotic
      renal diseases.

PMID- 15264184
TI  - A cross-sectional immunosurveillance study of anti-EPO antibody levels in CRF
      patients receiving epoetin alfa in 5 Ontario Renal Centers.
AB  - BACKGROUND: Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used
      successfully to correct the anemia of chronic renal failure for more than 12
      years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small
      number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA).
      To evaluate the utility of a large-scale anti-EPO antibody screening program in
      patients with chronic kidney disease (CKD) administered epoetin alfa, a study
      involving 5 large renal centers in southern Ontario, Canada, was conducted.
      METHODS: More than 1,500 hemodialysis, peritoneal dialysis, and predialysis
      patients were screened for the prevalence of anti-EPO antibodies by means of a
      radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD
      Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels
      also were measured. All samples that tested positive or borderline for antibodies
      were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay.
      RESULTS: Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline
      results were detected by means of RIP. PRCA previously was diagnosed in the
      patient with the low-positive antibody level; the patient was treated with
      cyclosporine and currently is being administered epoetin alfa with good response.
      The 3 patients with borderline antibody results manifested no clinical signs of
      PRCA. Neutralization assays performed on all 4 serum samples were negative for
      anti-EPO antibodies. CONCLUSION: Results from this surveillance study show that
      the prevalence of antibody to EPO in patients with CKD administered epoetin alfa
      in 5 Canadian renal centers is low, and the value of a large-scale antibody
      screening program for PRCA cannot be justified.

PMID- 15264185
TI  - Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured
      by thrombin generation time.
AB  - BACKGROUND: Patients with renal dysfunction who undergo systemic anticoagulation
      with enoxaparin are at increased risk for bleeding. Although there is decreased
      renal clearance of enoxaparin in this population, the clinical utility of
      monitoring antifactor Xa activity is controversial because it is weakly
      correlated to bleeding. The goal of this study was to investigate the role of
      other novel anticoagulation markers, such as thrombin generation time, platelet
      contractile force, and clot elastic modulus, while controlling for antifactor Xa
      activity in patients with and without renal dysfunction. METHODS: Thirty
      anticoagulant- and antiplatelet-naive subjects completed this trial (10 controls,
      10 patients with chronic kidney disease, and 10 patients with end-stage renal
      disease [ESRD]). Blood samples were obtained and spiked ex vivo with increasing
      concentrations of enoxaparin antifactor Xa activity (0.25, 0.5, 1.0, and 3.0
      IU/mL). Thrombin generation time, platelet contractile force, and clot elastic
      modulus were measured in each group at each antifactor Xa activity concentration.
      RESULTS: Subjects with ESRD had an approximately 50% greater anticoagulant
      effect, determined by thrombin generation time prolongation, than controls at
      antifactor Xa activity concentrations of 0.5 to 3.0 IU/mL. This may explain why
      subjects with ESRD with seemingly therapeutic antifactor Xa levels still
      experience adverse bleeding. There were no intergroup differences in platelet
      function, determined by platelet contractile force and clot elastic modulus.
      CONCLUSION: Antifactor Xa poorly predicts the degree of anticoagulation in
      patients with ESRD administered low-molecular-weight heparin (LMWH). Thrombin
      generation time may be a clinically useful anticoagulation monitoring tool to
      monitor LMWH therapy, especially in patients with renal dysfunction. Additional
      randomized prospective studies are needed to corroborate these findings.

PMID- 15264186
TI  - Removal of the protein-bound solute p-cresol by convective transport: a
      randomized crossover study.
AB  - BACKGROUND: Middle molecules (MMs) and protein-bound solutes are poorly removed
      by conventional hemodialysis (HD). Hemodiafiltration (HDF) combines convection
      and diffusion in a single therapy and has been shown to be superior for the
      elimination of several small and larger retention molecules. Information on the
      elimination of protein-bound solutes during convective strategies is scarce. The
      primary aim of this randomized crossover study is to evaluate the influence of
      internal filtration, postdilution HDF, and predilution HDF on removal of the
      protein-bound solute p-cresol. METHODS: Fourteen stable patients on regular
      thrice-weekly medium-flux HD therapy were assigned to 5 treatment periods of 2
      weeks each for: HD with HF80(S); HD with FX80; postdilution HDF, 20 L, with FX80;
      predilution HDF, 20 L, with FX80; and predilution HDF, 60 L, with FX80 (all
      dialyzers from Fresenius Medical Care, Bad Homburg, Germany). RESULTS: As for the
      water-soluble solutes, elimination of p-cresol was better during HDF and
      increased with greater filtration volumes. Removal of beta2-microglobulin
      (beta2m) also was enhanced during HDF. However, the positive effect of convection
      was offset when high predilution substitution volumes were applied, probably as a
      result of dilution. Within each dialytic approach, removal of the MM beta2m and
      the protein-bound solute p-cresol was significantly less than that of the water
      soluble molecules urea nitrogen and creatinine. CONCLUSION: Our data indicate
      that convection can provide superior protein-bound solute removal compared with
      high-flux HD. Our findings also suggest that better elimination of the unbound
      fraction is the most plausible underlying mechanism.

PMID- 15264187
TI  - Tyrosine nitration in plasma proteins from patients undergoing hemodialysis.
AB  - BACKGROUND: A growing body of evidence suggesting that oxidative stress might be
      one of the most important complications occurring during hemodialysis (HD) has
      accumulated. However, although the role of reactive oxygen species has been
      investigated extensively, little is known about the involvement of reactive
      nitrogen species. In the present investigation, levels of protein modifications
      in the form of tyrosine nitration in patients undergoing long-term HD therapy
      were evaluated. METHODS: Tyrosine nitration of plasma proteins was detected by
      means of Western blotting using a specific nitrotyrosine-recognizing monoclonal
      antibody, and band intensity was evaluated by using image analysis software.
      Immunoprecipitation of plasma proteins by antinitrotyrosine-agarose--conjugated
      antibodies, followed by Western blotting, was used in an attempt to identify the
      nitrated proteins. RESULTS: Although several proteins with nitrated tyrosine
      residues were observed in plasma of healthy individuals, increased nitration
      levels were observed in some specific proteins in all patients tested (n = 25)
      compared with controls (n = 6). At least 6 apparent bands appeared to be more
      nitrated than their counterparts in plasma from controls. Ceruloplasmin was
      identified as 1 of the proteins with significantly increased nitration in
      patients. CONCLUSION: Results of the present investigation show that specific
      plasma proteins of HD patients are post-translationally modified by nitration of
      their tyrosine residues. The nature of these proteins, as well as the exact
      molecular mechanisms and consequences of these modifications, warrant additional
      investigation.

PMID- 15264188
TI  - International variation in vitamin prescription and association with mortality in
      the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: The prevalence of water-soluble vitamin use among hemodialysis (HD)
      patients and whether mortality and hospitalization are associated with water
      soluble vitamin use by HD patients have not previously been reported. The present
      study investigates patterns of water-soluble vitamin use among HD patients in the
      Dialysis Outcomes and Practice Patterns Study (DOPPS) I and evaluates outcomes
      associated with vitamin use. METHODS: The study sample came from the DOPPS I, a
      prospective observational study of adult HD patients (N = 16,345) randomly
      selected from 308 representative dialysis facilities in France, Germany, Italy,
      Japan, Spain, the United Kingdom, and the United States. Time-dependent Cox
      regression models were used to assess relative risk (RR) for mortality and
      hospitalization for patients administered water-soluble vitamins versus those not
      administered water-soluble vitamins. RESULTS: There was large variation by region
      in the percentage of patients administered water-soluble vitamins: Europe ranged
      from a low of 3.7% in the United Kingdom to a high of 37.9% in Spain; 5.6% in
      Japan; and 71.9% in the United States. Patient use of water-soluble vitamins was
      associated with a substantially and significantly lower risk for mortality (RR,
      0.84; P = 0.001). Lower RR for facility-level mortality also was associated with
      greater water-soluble vitamin use (RR, 0.98; P = 0.05 per 10% more patients
      administered water-soluble vitamins at the facility). CONCLUSION: Although only a
      randomized trial could prove that water-soluble vitamins improve outcomes, use of
      water-soluble vitamins is a minimal-risk practice pattern associated with
      improved outcomes in this prospective observational study.

PMID- 15264189
TI  - The influence of serum apolipoprotein E concentration and polymorphism on serum
      lipid parameters in hemodialysis patients.
AB  - BACKGROUND: Apolipoprotein E (ApoE) polymorphism has been shown to influence
      serum lipid parameters and ApoE levels in both healthy subjects and hemodialysis
      (HD) patients. Conversely, ApoE concentration significantly affects serum lipid
      levels in the general population, independently of ApoE polymorphism, by
      modulating lipoprotein production, lipolytic conversion, and receptor-mediated
      clearance. Therefore, studying the effect of ApoE polymorphism on serum lipid
      levels without taking into account ApoE levels could lead to confounding results.
      However, such a combined study has not been performed in HD patients to date.
      METHODS: Three hundred one patients without diabetes on long-term maintenance HD
      therapy and 200 matched healthy subjects were studied. Determination of levels of
      fasting serum ApoE and other lipid parameters, as well as common ApoE genotypes,
      was performed in all subjects. RESULTS: HD patients had a significantly lower
      prevalence of the epsilon4 allele and greater levels of ApoE compared with the
      control population. ApoE2 allele carriers had significantly lower levels of ApoB
      and serum total, low-density lipoprotein, and non-high-density lipoprotein
      cholesterol, as well as increased ApoE levels. When ApoE levels were included in
      analysis, ApoE levels themselves were proven to be important determinants of
      serum lipid levels, whereas the effect of ApoE polymorphism became more
      pronounced. The combination of these 2 factors explains a much greater percentage
      of the variation in the studied parameters than each factor alone. CONCLUSION:
      For the first time, our study provides data to support that ApoE concentration in
      combination with the ApoE polymorphism significantly influences serum lipid
      parameters in HD patients.

PMID- 15264190
TI  - Differential management of cardiovascular disease in ESRD by nephrologists and
      cardiologists.
AB  - BACKGROUND: Mortality and morbidity from cardiovascular disease are high in
      patients with end-stage renal disease (ESRD). The cardiovascular profile of
      patients with ESRD may differ from that of the general population. We examined
      how nephrologists and cardiologists differ in managing hypertension and
      cardiovascular disease in patients with ESRD. METHODS: Seven cases incorporating
      relevant clinical and echocardiographic findings common to this population were
      developed based on a chart review of an ESRD population. Each ESRD case
      incorporated a clinical presentation designed to test for a specific dichotomous
      response to a common and important clinical problem. Nine nephrology and 7
      cardiology faculty members, each paired with a senior clinical fellow from the
      discipline, were surveyed. RESULTS: Nephrologists were less likely than
      cardiologists to initiate beta-blockade in patients with echocardiographic
      evidence of regional wall motion abnormalities if there was no history of
      coronary artery disease (CAD; P < 0.01). In patients with known CAD,
      cardiologists were more likely than nephrologists to intensify antihypertensive
      therapy, even in the setting of a history of fractures associated with
      orthostatic hypotension (P < 0.02). Decision making did not differ between
      subspecialists in the management of left ventricular hypertrophy, congestive
      heart failure, or diastolic dysfunction. CONCLUSION: Nephrologists and
      cardiologists differ in their management of hypertension in the presence of
      ischemic heart disease in the ESRD population. Only limited data specific to the
      ESRD population are available to assess which approach is superior. The
      discipline-driven differential management approaches observed emphasize the need
      for better evidence-based management strategies for this population.

PMID- 15264191
TI  - Colonic transit time in long-term dialysis patients.
AB  - BACKGROUND: Constipation is a frequent health concern for long-term dialysis
      patients. The increased incidence of constipation in long-term dialysis patients
      is based mainly on self-reported data. Our aim is to investigate this problem
      objectively by using colonic transit time in long-term hemodialysis (HD) and
      continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Segmental and
      total colonic transit time studies measured by means of radiopaque markers were
      conducted in 56 HD patients, 63 CAPD patients, and 25 healthy control subjects.
      Segmental colonic transit times were calculated separately for 3 segments of the
      colon (right, left, and rectosigmoid) and total transit time, which was the sum
      of all 3 segment times. RESULTS: Colonic transit time was significantly prolonged
      in HD patients (43.0 +/- 22.2 versus 32.7 +/- 13.7 hours in CAPD patients and
      24.3 +/- 11.9 hours in controls; P < 0.001). Increased colonic transit times in
      the right and rectosigmoid segments, but not the left segment, contributed to the
      prolongation in total colonic transit time. Age and interdialytic weight gain
      correlated well with prolongation of total and segmental colonic transit times in
      HD patients (P < 0.01). Diabetes and female sex in all groups were associated
      with longer total and segmental colonic transit times, but this trend was not
      statistically significant. CONCLUSION: Total, right segmental, and rectosigmoid
      segmental colonic transit times are prolonged in long-term HD patients compared
      with CAPD patients and healthy controls. We believe colonic transit time
      measurement is helpful to tailor therapy because it helps define the pathogenesis
      of constipation.

PMID- 15264192
TI  - Severe coronary stenosis is an important factor for induction and lengthy
      persistence of ventricular arrhythmias during and after hemodialysis.
AB  - BACKGROUND: Ventricular arrhythmias have been shown to be the major cause of
      sudden cardiac death in hemodialysis (HD) patients. We investigated whether
      angiographic coronary stenosis was responsible for the induction of ventricular
      arrhythmias in HD patients. METHODS: HD patients (n = 150) showing ischemic signs
      in exercise electrocardiography or echocardiography were divided into 2 groups:
      the stenotic group (n = 61), with significant coronary stenosis (> or =75% in
      diameter), and the nonstenotic group (n = 89), without significant coronary
      stenosis on coronary angiography. Severity of ventricular arrhythmias was
      evaluated by means of ambulatory 24-hour Holter monitoring in HD patients with
      and without significant coronary stenosis. RESULTS: The frequency of ventricular
      premature contractions and prevalence of patients with Lown class 4 ventricular
      arrhythmias were significantly greater in the stenotic than nonstenotic group
      during HD and for 12 hours after HD (P < 0.03). In the stenotic group, a
      significantly greater frequency of ventricular premature contractions and
      prevalence of patients with complex arrhythmias were observed during HD (1.33%
      and 31.1%, respectively) compared with before HD (0.50% and 11.5%, respectively),
      and the high incidence persisted for 6 hours after HD. In the nonstenotic group,
      a slightly increased incidence was observed only during HD compared with before
      HD. Multivariate analysis showed only coronary stenosis (odds ratio, 5.69; P =
      0.041) as an independent and significant factor for the induction of complex
      arrhythmias. CONCLUSION: These data clearly indicate that severe coronary
      stenosis, which may cause myocardial ischemia, is an important factor for the
      induction and lengthy persistence of ventricular arrhythmias during and after HD.

PMID- 15264193
TI  - Evaluation of the prevalence and risk factors for colonization by vancomycin
      resistant Enterococcus among patients on dialysis.
AB  - BACKGROUND: Vancomycin-resistant Enterococcus (VRE) has been reported among long
      term dialysis patients, although risk factors for VRE colonization are not well
      defined. This study aims to appraise the prevalence and risk factors for VRE
      colonization among patients on long-term dialysis therapy, as well as the
      mechanisms for dissemination of vancomycin resistance. METHODS: This is a cross
      sectional survey of 320 patients on long-term dialysis therapy at 2 hospitals of
      the Federal University of Sao Paulo from June 2001 to March 2003. Fecal samples
      were collected from each patient once a week for 1 month. Samples with positive
      test results for VRE were submitted to molecular typing through automated
      ribotyping. RESULTS: VRE prevalence was 14.4%. There were significant
      associations between VRE and dialysis type (hemodialysis, P = 0.04), number of
      hospitalizations (P = 0.03), low hemoglobin level (P = 0.03), and leukocytosis (P
      = 0.05). Among samples with VRE (n = 56), 25% were Enterococcus faecium; 10.7%,
      Enterococcus casseliflavus; 57.1%, Enterococcus gallinarum; and 3.6%,
      Enterococcus faecalis. All samples isolated were sensitive to teicoplanin, except
      for E faecium samples, which were strongly resistant, although 9 of 14 patients
      with this isolate presented the same ribogroup (111-S-4). Typing of 6 samples
      from 8 dialysis patients with E gallinarum was performed, showing a predominant
      ribogroup (112-S-4). CONCLUSION: Hospital environment, hemodialysis, anemia, and
      leukocytosis appear to be associated with VRE colonization. These results suggest
      that dissemination of these bacteria among patients on long-term dialysis therapy
      may be taking place.

PMID- 15264194
TI  - Access to renal transplantation among American Indians and Hispanics.
AB  - BACKGROUND: African Americans have decreased access to renal transplantation
      compared with whites. Whether similar barriers exist for American Indians or
      Hispanics is not well defined. METHODS: The authors identified a total of 1,335
      patients ages 20 to 59 years without prior renal transplantation undergoing
      dialysis in December 1994 in Arizona and New Mexico. For each patient,
      information was collected on identification as a potential candidate for renal
      transplantation, referral to a renal transplantation center, completion of 4
      stages in the evaluation process, and receipt of a transplant over 7 years.
      RESULTS: American Indians were more likely than whites to be identified as
      potential candidates (relative risk [RR] 1.30, 95% confidence interval [CI] 1.15
      to 1.44) and to be referred to a transplant center (RR 1.16, 95% CI 1.09 to
      1.19). There were no significant differences in candidacy or referral status
      between Hispanics and whites. Among potential candidates referred to a transplant
      center, both American Indians (RR 0.73, 95% CI 0.51 to 0.96) and Hispanics (RR
      0.68, 95% CI 0.50 to 0.88) were less likely than whites to be placed on a waiting
      list. Both American Indians (hazard ratio [HR] 0.37, 95% CI 0.24 to 0.58) and
      Hispanics (HR 0.58, 95% CI 0.39 to 0.86) were much less likely than whites to
      undergo renal transplantation. CONCLUSION: Despite similar referral rates for
      renal transplantation, American Indians and Hispanics were less likely than
      whites to be placed on a transplant waiting list or receive a transplant.
      Policies to address these disparities should address specific barriers within the
      transplant evaluation process.

PMID- 15264195
TI  - Late urinary tract infection after renal transplantation in the United States.
AB  - BACKGROUND: Although urinary tract infection (UTI) occurring late after renal
      transplantation has been considered "benign," this has not been confirmed in a
      national population of renal transplant recipients. METHODS: We conducted a
      retrospective cohort study of 28,942 Medicare primary renal transplant recipients
      in the United States Renal Data System (USRDS) database from January 1, 1996,
      through July 31, 2000, assessing Medicare claims for UTI occurring later than 6
      months after transplantation based on International Classification of Diseases,
      9th Revision (ICD-9), codes and using Cox regression to calculate adjusted hazard
      ratios (AHRs) for time to death and graft loss (censored for death),
      respectively. RESULTS: The cumulative incidence of UTI during the first 6 months
      after renal transplantation was 17% (equivalent for both men and women), and at 3
      years was 60% for women and 47% for men (P < 0.001 in Cox regression analysis).
      Late UTI was significantly associated with an increased risk of subsequent death
      in Cox regression analysis (P < 0.001; AHR, 2.93; 95% confidence interval [CI],
      2.22, 3.85); and AHR for graft loss was 1.85 (95% CI, 1.29, 2.64). The
      association of UTI with death persisted after adjusting for cardiac and other
      infectious complications, and regardless of whether UTI was assessed as a
      composite of outpatient/inpatient claims, primary hospitalized UTI, or solely
      outpatient UTI. CONCLUSION: Whether due to a direct effect or as a marker for
      serious underlying illness, UTI occurring late after renal transplantation, as
      coded by clinicians in the United States, does not portend a benign outcome.

PMID- 15264196
TI  - Membranous glomerulonephritis in a patient with an adrenal ganglioneuroma.
AB  - Membranous glomerulonephritis has been reported in association with several
      tumors. This report is the first case of membranous glomerulonephritis associated
      with an adrenal ganglioneuroma. The sera obtained from the patient at
      presentation stained the fibrillary component of the ganglioneuroma and the
      glomerular basement membrane of the kidney. The antibodies present in the
      patient's serum also reacted with the glomerular basement membrane of several
      normal and randomly selected abnormal kidneys, including 1 from a patient with
      Alport's syndrome. The patient's sera contained a circulating tumor antigen
      specific antibody that cross-reacted with an antigen present on the podocyte
      membrane of the renal glomeruli. The resection of the ganglioneuroma resulted in
      a complete remission of the nephrotic syndrome within months of removal of the
      tumor. This was associated with loss of antibodies in the patient's serum. The
      patient was not treated with steroids or any immunosuppressive agents. The
      patient remains in remission with normal renal function after 9 years of follow
      up.

PMID- 15264197
TI  - Hypertension.

PMID- 15264198
TI  - Primary renal allograft dysfunction.

PMID- 15264200
TI  - Clinical significance of the K/DOQI bone guidelines in Japan.

PMID- 15264204
TI  - Quiz page. Tubular epithelial injury consistent with osmotic nephrosis.

PMID- 15264206
TI  - Asaia bogorensis peritonitis identified by 16S ribosomal RNA sequence analysis in
      a patient receiving peritoneal dialysis.
AB  - Here the authors report a case of refractory peritonitis leading to multiple
      hospitalizations and the loss of peritoneal dialysis access in a patient on
      automated peritoneal dialysis, caused by Asaia bogorensis, a bacterium not
      previously described as a human pathogen. This organism was identified by
      sequence analysis of the 16S ribosomal RNA gene. Unusual microbial agents may
      cause peritonitis, and molecular microbiological techniques are important tools
      for identifying these agents.

PMID- 15264207
TI  - Traumatic calcinosis cutis in a dialysis patient.
AB  - A patient with end-stage renal disease and refractory hyperparathyroidism was
      evaluated for acute-onset thickening and hardening of the skin of the lower
      extremities. Her clinical course and physical examination findings were
      consistent with the recently described entity of nephrogenic fibrosing
      dermopathy. However, skin biopsy results showed metastatic and dystrophic
      calcification, without calcific uremic arteriolopathy (calciphylaxis). The
      patient reported a history of self-inflicted trauma; the authors postulate that
      trauma, in the setting of hyperparathyroidism and an elevated serum calcium
      phosphorous product, resulted in the subcutaneous deposition of calcium salts. To
      the authors' knowledge, this is the first report of metastatic and dystrophic
      calcification, without calciphylaxis, in a patient with refractory
      hyperparathyroidism. This case underscores both the rich variety of skin
      conditions seen in patients undergoing dialysis and recent developments in the
      field of dermatologic disorders associated with end-stage renal disease.

PMID- 15264208
TI  - Three siblings with steroid-resistant nephrotic syndrome: new NPHS2 mutations in
      a Turkish family.
AB  - Steroid-resistant nephrotic syndromes often are resistant to additional
      immunosuppressive agents and tend to progress to end-stage renal disease. Genetic
      studies in children with familial nephrotic syndrome have identified mutations in
      genes that encode important podocyte proteins. NPHS2 mutations are responsible
      for autosomal recessive familial focal segmental glomerulosclerosis (FSGS), and
      these mutations were detected in both familial and sporadic forms of FSGS.
      Interethnic differences were suggested to play a role in the incidence of these
      mutations. In this report, the cases of 3 siblings with steroid-resistant
      nephrotic syndrome who carry NPHS2 mutations (R238S and P118L) are presented.

PMID- 15264209
TI  - Telithromycin-induced acute interstitial nephritis: a first case report.
AB  - Telithromycin, a ketolide antibiotic used for the treatment of community-acquired
      respiratory infections, is widely prescribed in primary care practice. Treatment
      related adverse events are mainly of gastrointestinal origin and generally mild
      in intensity. The authors report the first case of telithromycin-induced severe
      acute interstitial nephritis. Practitioners should be aware of the possibility
      that telithromycin therapy could result in this form of drug-induced acute renal
      failure.

PMID- 15264210
TI  - Peritoneal dialysis catheter obstruction caused by Fallopian tube wrapping.
AB  - Peritoneal catheter malfunction is commonly related to omental wrapping, although
      entrapment owing to other different intraperitoneal structures is possible but
      rare. The authors report a case of catheter obstruction owing to fallopian tube
      wrapping, diagnosed and resolved by laparoscopic surgery. A brief review of this
      rare problem is presented.

PMID- 15264211
TI  - Development of transgenic mice that inducibly express an active form of c-Src in
      the epidermis.
AB  - Recent work from our laboratory has shown that elevated src kinase activity
      enhances tumor promotion, malignant progression, and metastasis during multistage
      skin carcinogenesis. In this study, we have generated "gene-switch" src(530)
      transgenic mice to further analyze the role of this nonreceptor tyrosine kinase
      in multistage carcinogenesis. Target transgenic mice that have an activated form
      of the human c-src (src(530)) gene fused with GAL4 binding sites upstream of the
      thymidine kinase (TK) promoter were generated. Two lines of epidermis-specific
      transactivator mice were used that targeted the expression of GLVPc or GLp65
      transactivators, fusion molecules containing a truncated progesterone receptor
      with a GAl4-DNA binding domain, with either a mouse loricrin (ML) or human
      keratin 14 (HK14) promoter, respectively. The transactivator mice (ML.GLVPc or
      HK14.GLp65) and the target mice (TK.src(530)) were mated to generate bitransgenic
      mice, and src(530) transgene expression was induced by topical application of
      RU486 (mifepristone, a progesterone receptor antagonist). In both
      ML.GLVPc/TK.src(530) and HK14.GLp65/TK.src(530) bitransgenic mice, histological
      analysis revealed that only the bitransgenic mice had marked epidermal
      hyperplasia and hyperkeratosis after treatment with RU486. Neither the
      nontransgenic mice nor the mice hemizygous for either the transactivator
      transgene or the target transgene alone showed any response to treatment with
      RU486. In addition, no differences were observed in the skin of the bitransgenic
      mice versus nontransgenic littermates without treatment of RU486. Interestingly,
      in HK14.GLp65/TK.src(530) bitransgenic mice, squamous cell carcinomas (SCCs)
      arose along the periphery of the area of the punch biopsies in 25% of the
      bitransgenic mice several weeks after taking the biopsy and subsequent to RU486
      treatment. Collectively, the data support a role of c-src activation in epidermal
      hyperproliferation. Furthermore, the data support the conclusion that src
      activation can substitute for an initiating event in the presence of a tumor
      promoting stimulus (i.e., wounding). Finally, inducible src(530) transgenic mice
      provide a new tool for dissecting the role of src activation in multistage
      carcinogenesis by allowing temporal control of the expression of this oncogene.

PMID- 15264212
TI  - Plumbagin induces reactive oxygen species, which mediate apoptosis in human
      cervical cancer cells.
AB  - There is an emerging evidence that plumbagin (5-hydroxy-2-methyl-1, 4
      naphthoquinone) may have potential as a chemotherapeutic agent. However, the
      growth inhibitory mechanisms of plumbagin have remained unexplored. The aim of
      the study was to determine whether plumbagin-induced cell death in human cervical
      cancer cell line, ME-180, exhibited biochemical characteristics of apoptosis and
      to check whether N-acetyl-l-cysteine (NAC), which is a free radical scavenger,
      can reverse the cytotoxic effects of plumbagin. It can be concluded from the
      results that plumbagin inhibits the growth of ME-180 cells in a concentration and
      time-dependent manner. The cytotoxic effect of plumbagin induced cell death is
      through the generation of reactive oxygen species (ROS) and subsequent induction
      of apoptosis as demonstrated by the present data. Treatment of cells with
      plumbagin caused loss of mitochondrial membrane potential (DeltaPsi(m)), and
      morphological changes characteristic of apoptosis, such as the translocation of
      phosphatidyl serine, nuclear condensation, and DNA fragmentation. Moreover,
      plumbagin-induced apoptosis involved release of mitochondrial cytochrome c and
      apoptosis inducing factor (AIF), thus activation of caspase-dependent and 
      independent pathways, as shown by the plumbagin-mediated activation of caspase-3
      and -9. Our results also show that pretreatment of ME-180 cells with NAC blocks
      plumbagin-induced loss of DeltaPsi(m) and subsequent release of cytochrome c,
      AIF, and caspase-9 and -3 activation, thus inhibiting the apoptotic ability of
      plumbagin.

PMID- 15264213
TI  - Nkx2.1 transcription factor in lung cells and a transforming growth factor-beta1
      heterozygous mouse model of lung carcinogenesis.
AB  - The Nkx2.1 homeobox gene and transforming growth factor-beta1 (TGF-beta1) are
      essential for organogenesis and differentiation of the mouse lung. NKX2.1 is a
      marker of human lung carcinomas, but it is not known whether this gene
      participates in early tumorigenesis. Addition of TGF-beta1 to TGF-beta1
      responsive nontumorigenic mouse lung cells cotransfected with a NKX2.1Luc
      luciferase reporter and either a Sp1 or Sp3 plasmid showed a significant increase
      or decrease, respectively, in NKX2.1Luc transcription. Cotransfection of Sp3 and
      dominant-negative TGF-beta type II receptor plasmids negated the effect of Sp1.
      Cotransfected Sp1 plasmid with either dominant-negative Smad2 or Smad3 or Smad4
      plasmids significantly decreased NKX2.1Luc transcription. Electrophoretic
      mobility shift assays revealed binding of Sp1 and Smad4 to the NKX2.1 promoter.
      With a TGF-beta1 heterozygous mouse model, Nkx2.1 mRNA and protein in lungs of
      TGF-beta1 heterozygous mice were significantly lower compared to wildtype (WT)
      littermates. Competitive reverse transcription (RT)-polymerase chain reaction
      (PCR) and immunostaining showed that Nkx2.1 mRNA and protein decreased
      significantly in adenomas and adenocarcinomas compared to normal lung tissue. Our
      in vitro data showed that regulation of Nkx2.1 by TGF-beta1 occurs through TGF
      beta type II receptor and Smad signaling, with Sp1 and Sp3 in lung cells. Our in
      vivo data showed reduced Nkx2.1 in lungs of TGF-beta1 heterozygous mice compared
      to WT mice, that is detectable in adenomas, and that is further reduced in
      carcinogenesis, and that correlates with reduction of Sp1, Sp3, and Smads in lung
      adenocarcinomas. Our findings suggest that reduced Nkx2.1 and TGF-beta1 signaling
      components may contribute to tumorigenesis in the lungs of TGF-beta1 heterozygous
      mice.

PMID- 15264214
TI  - Inducible nitric oxide synthase expression in N-nitrosomethylbenzylamine (NMBA)
      induced rat esophageal tumorigenesis.
AB  - Nitric oxide (NO), an important regulatory molecule for immune response and
      cytotoxicity, is endogenously generated from L-arginine by NO synthase (NOS). One
      mechanism for NO-induced cytotoxicity is through its interaction with superoxide
      to produce peroxynitrite, which causes DNA damage. Three distinct isoforms of NOS
      have been isolated and represent the products of three different genes. The
      inducible form, inducible nitric oxide synthase (iNOS), is a mediator of
      inflammation and a regulator of epithelial cell growth. Upregulation of iNOS has
      been linked to epithelial tumorigenesis in various human and animal tissues. In
      the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)
      induced preneoplastic and papillomatous lesions of the rat esophagus were
      characterized for expression of iNOS. F344 rats were injected subcutaneously with
      NMBA (0.5 mg/kg body weight) three times per week for 5 wk. At 3, 6, 9, 12, 15,
      18, 21, 24, 30, and 36 wk following initiation of NMBA treatment, esophagi were
      collected from 12 untreated and 12 NMBA treated animals. Results of reverse
      transcription (RT)-polymerase chain reaction (PCR) and immunohistochemistry
      demonstrated a correlation between the upregulation of iNOS and neoplastic
      progression in the rat esophagus. The expression of iNOS mRNA in preneoplastic
      tissues and papillomas was significantly elevated when compared to normal
      tissues. Immunohistochemical analysis showed more extensive cytoplasmic staining
      of iNOS protein in preneoplastic tissues and papillomas than in normal tissues.
      Our data suggest, therefore, that the production of iNOS by the epithelium of the
      esophagus is associated with the development of NMBA-induced esophageal
      tumorigenesis in rats.

PMID- 15264215
TI  - Alterations of the Dutt1/Robo1 gene in lung adenocarcinomas induced by N
      nitrosobis(2-hydroxypropyl)amine in rats.
AB  - Abnormalities of tumor suppressor genes (TSGs) on chromosome 3p are known to be
      important for the development of human lung cancers. In the present study, we
      investigated alterations of the Dutt1/Robo1 gene, as a possible tumor suppressor
      in this region, in rat lung adenocarcinomas induced by N-nitrosobis(2
      hydroxypropyl)amine (BHP). Male Wistar rats, 6-wk-old, were given 2000 ppm BHP in
      their drinking water for 12 wk and maintained without further treatment until
      killed at wk 25. A total of 12 lung adenocarcinomas were obtained and total RNAs
      were extracted from each for assessment of aberrant transcripts of the
      Dutt1/Robo1 gene by reverse transcription (RT)-polymerase chain reaction (PCR)
      analysis. Aberrant transcripts bearing deletions of nucleotides (nt) 55-4318, 89
      4346, 605-4221, and 929-4318 were detected in four of 12 adenocarcinomas (33.3%).
      Loss or reduced expression of the Dutt1/Robo1 gene was not found in any of the
      adenocarcinomas. Genomic DNAs extracted from six adenocarcinomas for Southern
      blot analysis did not show any evidence of deletion or gross rearrangement of the
      Dutt1/Robo1 gene. These results suggest that alterations of the Dutt1/Robo1 gene
      may be involved in the development of some lung adenocarcinomas induced by BHP in
      rats.

PMID- 15264216
TI  - Nerve growth factor-induced protein kinase C stimulation contributes to TrkA
      dependent inhibition of p75 neurotrophin receptor sphingolipid signaling.
AB  - Previous studies have established that reciprocal interactions between the low
      affinity p75 nerve growth factor (NGF) receptor (p75(NTR)) and the high-affinity
      TrkA NGF receptor can dictate the cellular response to NGF. As the most important
      interaction, TrkA signaling was found to inhibit p75(NTR)-mediated
      sphingomyelinase (SMase) stimulation, ceramide production, and apoptosis.
      However, the mechanism by which TrkA counteracts p75(NTR)-coupled sphingolipid
      signaling is still unclear. Considering the stimulatory effect of NGF on protein
      kinase C (PKC) activity, we investigated the role of PKC in TrkA/p75(NTR)
      signaling interaction. In this study, we found that, in SK-N-BE cells, which
      selectively express p75(NTR), phorbol ester-induced PKC stimulation resulted in
      the abrogation of SMase stimulation and ceramide production induced by NGF.
      Moreover, in SK-N-BE neuroblastoma cells, which selectively express TrkA, NGF
      stimulated global PKC activity through two independent pathways involving
      phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase (PI3K). In SH-SY5Y,
      another neuroblastoma cell line, which coexpresses TrkA and p75(NTR), NGF induced
      PKC stimulation through a TrkA/PI3K signaling pathway, whereas there was no
      ceramide production. However, in these cells, the inhibition of TrkA, PI3K, and
      PKC resulted in the restoration of NGF-induced ceramide production. Thus, our
      study demonstrates for the first time that TrkA interferes with p75(NTR)
      signaling through a PI3K/PKC-dependent mechanism.

PMID- 15264217
TI  - Human skin-derived stem cells migrate throughout forebrain and differentiate into
      astrocytes after injection into adult mouse brain.
AB  - Recent evidence indicates that neural stem cell properties can be found among a
      mammalian skin-derived multipotent population. A major barrier in the further
      characterization of the human skin-derived neural progenitors is the inability to
      isolate this population based on expression of cell surface markers. Our work has
      been devoted to purified human skin-derived stem cells that are capable of neural
      differentiation, based on the presence or absence of the AC133 cell surface
      marker. The enriched skin-derived AC133(+) cells express the CD34 and Thy-1
      antigens. These cells cultured in a growth medium containing epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF) proliferate, forming
      spheres, and differentiate in vitro into neurons, astrocytes, and rarely into
      oligodendrocytes. Single cells from sphere cultures initiated from human purified
      AC133(+) cells were replated as single cells and were able to generate new
      spheres, demonstrating the self-renewing ability of these stem cell populations.
      Brain engraftment of cells obtained from human purified AC133(+)-derived spheres
      generated different neural phenotypes: immature neurons and a most abundant
      population of well differentiated astrocytes. The AC133-derived astrocytes
      assumed perivascular locations in the frontal cortex. No donor-derived
      oligodendrocytes were found in the transplanted mouse brains. Several donor
      small, rounded cells that expressed endothelial markers were found close to the
      host vessel and near the subventricular zone. Thus, mammalian skin AC133-derived
      cells behave as a multipotent population with the capacity to differentiate into
      neural lineages in vitro and, prevalently, endothelium and astrocytes in vivo,
      demonstrating the great plasticity of these cells and suggesting potential
      clinical application.

PMID- 15264218
TI  - Cyclic AMP/protein kinase a signal attenuates Ca(2+)-induced fibroblast growth
      factor-1 synthesis in rat cortical neurons.
AB  - Fibroblast growth factor (FGF)-1 is increased in particular brain regions after
      birth, suggesting an involvement of some regulatory neuronal circuits. To address
      the neuronal activity responsible for FGF-1 synthesis, effects of various
      neurotransmitter receptor activation on cellular FGF-1 content were examined
      using cultured rat cortical neurons. Histamine, glutamate, carbachol, serotonin
      or gamma-aminobutyric acid (GABA) caused an increase of FGF-1 content. Because
      this effect was mimicked by (1) N-methyl-D-aspartate, a glutamatergic agonist;
      (2) Ca(2+) ionophore; (3) depolarization with high concentration of KCl, but was
      abolished in Ca(2+)-free medium, Ca(2+) influx was thought to trigger FGF-1
      synthesis. Such Ca(2+)-mediated enhancement of FGF-1 synthesis, however, did not
      occur in the presence of norepinephrine (NE), but was restored by KT-5720, an
      inhibitor of protein kinase A (PKA), suggesting an interplay between Ca(2+)
      activated and cAMP/PKA signals for neuronal FGF-1 synthesis. This mechanism was
      proved to function in vivo by stimulation of FGF-1 expression in neurons of the
      cerebral cortex after intracerebral administration of propranolol, an antagonist
      of adrenergic beta receptors. This demonstrates that FGF-1 synthesis is
      essentially upregulated by Ca(2+) influx through excitatory neuronal activities,
      but such an effect is abolished by neurotransmission that evokes cAMP/PKA
      signals. FGF-1 produced is thought to act on establishment and maintenance of
      particular neuronal circuits in the brain, which may be one of the ways
      neurotransmitters regulate brain function.

PMID- 15264219
TI  - Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence
      affect plasma membrane targeting, ligand binding, and calcium influx in
      heterologous mammalian cells.
AB  - The serotonin type 3(A) receptor (5-HT3(A)R) is a ligand-gated ion channel (LGIC)
      that modulates a diverse set of cognitive and physiological functions. The 5
      HT3(A)R, as with other LGICs, is a pentameric ion channel comprising five
      glycoprotein subunits. Although the N-terminal of the 5-HT3(A)R contains three
      putative N-linked glycosylation sites, the importance of each glycosylation site
      has not yet been established. To address this question, we used tunicamycin
      treatment and site-directed mutagenesis to inhibit selectively N-linked
      glycosylation at each site and then examined the effects of these treatments on
      receptor expression and function in transiently transfected heterologous cells.
      We show that the murine 5-HT3(A)R is glycosylated and that each N-linked
      glycosylation site plays a role in receptor regulation. Our findings suggest that
      N109 is necessary for receptor assembly, whereas N174 and N190 are important for
      plasma membrane targeting and ligand binding. Furthermore, we demonstrate that
      each site is necessary for 5-HT3(A)R-mediated Ca(2+) influx. We conclude that N
      glycosylation is a critical step in the maturation, trafficking, and function of
      the murine 5-HT3(A)R.

PMID- 15264220
TI  - Genetic background markedly influences vulnerability of the hippocampal neuronal
      organization in the "twitcher" mouse model of globoid cell leukodystrophy.
AB  - The twitcher mouse is well known as a naturally occurring authentic mouse model
      of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic
      deficiency of lysosomal galactosylceramidase. The twitcher mice used most
      commonly are on the C57BL/6J background. We generated twitcher mice that were on
      the mixed background of C57BL/6J and 129SvEv, the standard strain for production
      of targeted mutations. Twitcher mice on the mixed background were smaller and had
      a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice
      on the mixed background developed generalized seizures around 30 days that were
      never seen in twitcher mice on the C57BL/6J background. Neuropathologically,
      although the degree of the typical demyelination with infiltration of macrophages
      was similar in the central and peripheral nervous systems, in both strains,
      marked neuronal cell death was observed only in twitcher mice on the mixed
      background. In the hippocampus, the neuronal cell death occurred prominently in
      the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas.
      This neuropathology has never been seen in twitcher mice on the C57BL/6J
      background. Biochemically, the brain of twitcher mice on the mixed background
      showed much greater accumulation of lactosylceramide. Genetic background must be
      carefully taken into consideration when phenotype of mutant mice is evaluated,
      particularly because most targeted mutants are initially on a mixed genetic
      background and gradually moved to a pure background. These findings also suggest
      an intriguing possibility of important function of some sphingolipids in the
      hippocampal neuronal organization and maintenance.

PMID- 15264221
TI  - Expression and location of mRNAs encoding multiple forms of secretory
      phospholipase A2 in the rat retina.
AB  - Low-molecular-weight secretory phospholipases A(2) (sPLA(2)s) are a subgroup of
      PLA(2)s, which are secreted, bind to receptors, and may act as intercellular
      signaling modulators. At least 10 different groups have been characterized in
      mammals, and there is expanding evidence of the significance of sPLA(2)s in
      neuronal signaling and survival [Kolko et al. (1996) J. Biol. Chem. 271: 32722
      32728]. To date, no retinal sPLA(2)s have been cloned or characterized. We
      evaluated the existence and abundance of sPLA(2) subtypes in rat retina and
      explored their possible involvement in light-induced retinal damage. We designed
      primers to identify the sPLA(2)s in rat retina, based on known sequences of
      sPLA(2)-specific mRNAs in other tissues. RNA was isolated from rat retina, and
      cDNA was produced and used for PCR cloning to identify the novel subtypes of
      sPLA(2). Our study revealed the presence of mRNAs encoding sPLA(2)-IB, -X, -V, 
      IIE, -IIA, and -IIF in the retina, and quantification by real-time PCR revealed
      different abundances of the sPLA(2)s. We showed a time-dependent gene induction
      of sPLA(2)-X, -IB, and -V in light-induced retinal damage. We further explored
      the location of sPLA(2)-IB by in situ hybridization and immunohistochemistry.
      This study is the first to reveal the presence, abundance, and induction of mRNAs
      encoding sPLA(2)s in rat retina. We suggest that these enzymes are themselves
      intercellular signaling modulators of retinal cell function and perhaps also of
      retinal degeneration.

PMID- 15264222
TI  - Interplay among platelet-activating factor, oxidative stress, and group I
      metabotropic glutamate receptors modulates neuronal survival.
AB  - Platelet-activating factor (PAF) is a potent phospholipid messenger in the
      nervous system that participates in synaptic plasticity and in pathologic
      processes, including neurodegeneration. Oxidative stress plays important roles in
      neuronal cell death. To define the interaction between PAF and oxidative radicals
      in neuronal death, we studied the effects of PAF in the presence of oxidative
      radicals in primary neurons in culture. Exogenous PAF (50 microM) caused PAF
      receptor-independent injury to neurons. A nonneurotoxic PAF concentration (500
      nM) potentiated neuronal death caused by hydrogen peroxide as determined by
      lactate dehydrogenase (LDH) assay, Hoechst staining, and TUNEL analysis, but it
      did not potentiate neuronal death caused by menadione, a superoxide donor, or by
      the nitric oxide donors 3-morpholino-sydnonimine (SIN-1) and sodium nitroprusside
      (SNP). This potentiation of the hydrogen peroxide effect was selectively blocked
      by a PAF membrane-receptor antagonist, BN52021 (5 microM). The neurotoxic effect
      of PAF and hydrogen peroxide was also completely blocked by ebselen and partially
      decreased by pretreatment with (S)-3,5-dihydroxyphenylglycine (DHPG), a group I
      metabotropic glutamate receptor (mGluR) agonist. This study suggests that PAF
      receptor antagonists may be useful for neuroprotection. A similar effect might
      also be obtained with group I mGluR agonists, probably by way of a different
      underlying mechanism.

PMID- 15264224
TI  - Redox regulation of glial inflammatory response to lipopolysaccharide and
      interferongamma.
AB  - Astrocytes and microglia, the two immune-regulatory cells of the central nervous
      system (CNS), are activated by a variety of pathogens and cytokines to elicit
      rapid transcriptional responses. This program of activation is initiated by a set
      of intracellular signaling cascades that includes mitogen-activated protein
      kinase (MAPK), nuclear factor (NF) kappaB, and Janus kinase/signal transducers
      and activators of transcription (JAK/STAT) pathways. This study defines the
      critical role that NADPH oxidase(Phox)-derived reactive oxygen species (ROS) play
      in lipopolysaccharide (LPS)- and interferon (IFN)gamma-induced signaling cascades
      leading to gene expression in glial cells. Treatment of rat microglia and
      astrocytes with LPS and IFNgamma resulted in a rapid activation of Phox and the
      release of ROS followed by an induction of inducible nitric oxide synthase (iNOS)
      expression. iNOS induction was blocked by inhibitors of Phox, i.e., diphenylene
      iodonium chloride (DPI) and 4-(2-aminoethyl) benzenesulfonylfluoride (AEBSF),
      suggesting an involvement of ROS signaling in iNOS gene expression. Exogenous
      catalase but not superoxide dismutase suppressed the basal activity and
      completely blocked induced levels of NO/iNOS, suggesting that hydrogen peroxide
      is the ROS involved. Phox inhibitors and catalase also suppressed LPS/IFNgamma
      induced expression of cytokines, i.e., interleukin (IL)-1, IL-6, and tumor
      necrosis factor (TNF)alpha and blocked LPS activation of MAP kinases (i.e., p38
      MAPK, c-Jun N-terminal kinase and extracellular signal-regulated kinase),
      NFkappaB, and IFNgamma-induced STAT1 phosphorylation. A microglial cell line
      stably transfected with a mutant form of Phox subunit, i.e., p47(phox) W(193)R,
      and primary astrocytes derived from Phox-deficient mice showed attenuated ROS
      production and induction of iNOS in response to LPS/IFNgamma, further
      strengthening the notion that Phox-derived ROS are crucial for proinflammatory
      gene expression in glial cells.

PMID- 15264223
TI  - Effects of apolipoprotein E on the human immunodeficiency virus protein Tat in
      neuronal cultures and synaptosomes.
AB  - Human immunodeficiency virus type 1 (HIV-1)-associated dementia is observed in 20
      30% of patients with acquired immunodeficiency syndrome (AIDS). The epsilon4
      allele of the apolipoprotein E (APOE) gene currently is thought to play a role as
      a risk factor for the development of HIV dementia. The HIV protein Tat is
      neurotoxic and binds to the same receptor as apoE, the low-density lipoprotein
      receptor-related protein (LRP). In this study, we investigated the role apoE
      plays in Tat toxicity. Synaptosomes from wild-type mice treated with Tat had
      increased reactive oxygen species (ROS), increased lipid and protein oxidation,
      and decreased mitochondrial membrane potential. Synaptosomes from APOE-knockout
      mice also had increased ROS, increased protein oxidation, and decreased
      mitochondrial membrane potential, but to a significantly lesser degree. Treatment
      of synaptosomes with heparinase and Tat increased Tat-induced oxidative stress,
      consistent with the notion of Tat requiring interaction with neuronal membranes
      to induce oxidative damage. Human lipidated apoE3 greatly protected neurons from
      Tat-induced toxicity, whereas human lipidated apoE4 showed no protection. We
      demonstrated that human apoE3 has antioxidant properties against Tat-induced
      toxicity. Taken together, the data suggest that murine apoE and human apoE4 act
      similarly and do not protect the cell from Tat-induced toxicity. This would allow
      excess Tat to remain outside the cell and interact with synaptosomal membranes,
      leading to oxidative stress and neurotoxicity, which could contribute to dementia
      associated with HIV. We show that the antioxidant properties of apoE3 greatly
      outweigh the competition for clearance in deterring Tat-induced oxidative stress.

PMID- 15264225
TI  - NGF acts via p75 low-affinity neurotrophin receptor and calpain inhibition to
      reduce UV neurotoxicity.
AB  - The relative roles of the high-affinity nerve growth factor (NGF) receptor, TrkA,
      and low-affinity p75 neurotrophin receptor (p75NTR) in neuronal survival are an
      active research area. We reported previously that UV treatment induces a calpain
      dependent, delayed neuronal death. We show here that NGF inhibits this UV-induced
      cortical neuron death. Interestingly, NGF neuroprotection requires p75NTR.
      Because it has been reported that NGF binding to p75NTR leads to ceramide
      generation, we evaluated whether ceramide was also neuroprotective. We found that
      ceramide also inhibits UV toxicity, and that the actions of ceramide and NGF were
      not additive. Moreover, cycloheximide inhibited ceramide and NGF neuroprotection,
      suggesting that their actions require new protein synthesis. Consistent with this
      possibility, we found that NGF activates the expression of genes such as
      calbindin. Lastly, we explored the role of calpain in NGF actions. NGF and
      ceramide both reduced the level of calpain activation after UV treatment. This
      NGF effect was p75NTR dependent. Overall, we interpret these results as
      consistent with an NGF neuroprotective pathway wherein p75NTR activation leads
      sequentially to ceramide generation, new protein synthesis, and inhibition of
      calpain activation. Overall, these results provide insight into a p75NTR
      dependent pathway of NGF neuroprotection.

PMID- 15264226
TI  - Steady plasma concentration of unfractionated heparin reduces infarct volume and
      prevents inflammatory damage after transient focal cerebral ischemia in the rat.
AB  - Unfractionated heparin (UH) decreases the extent of infarction after transient
      focal brain ischemia in the rat and abridges neuroinflammatory damage in patients
      with acute stroke. This study was aimed at assessing whether controlled and
      steady heparinemia in plasma can reduce infarct volume and exert neuroprotective
      effects after ischemia. Infarct volume was measured at 24 and 7 days following a
      1-hr intraluminal middle cerebral artery (MCA) occlusion in rats treated with UH
      or with vehicle. After testing several UH administration protocols, we choose to
      give a bolus of 200 U/kg, which was started 3 hr after the occlusion, followed by
      a 24-hr intraperitoneal perfusion of 70 U/kg/hr, which maintained a 24-hr steady
      plasma heparinemia (0.3-0.6 U/ml) and caused no CNS or systemic bleeding. In
      addition, plasma IL-10 concentration was measured by ELISA, endothelial VCAM-1
      expression was evaluated by i.v. injection of a (125)I-labeled monoclonal
      antibody against VCAM-1, and brain hemeoxygenase-1 (HO-1) expression was
      determined by Western blot. UH-treated rats showed smaller infarctions than rats
      treated with vehicle, as well as higher IL-10 plasma levels and HO-1 brain
      expression and lower endothelial VCAM-1 induction. The study shows that a stable
      plasma concentration of UH given at nonhemorrhagic doses reduces infarct volume
      after ischemia-reperfusion in the rat. It also shows that UH prevented the
      induction of cell adhesion molecules in the cerebral vasculature and increased
      the expression of molecules with antiinflammatory and prosurvival properties.
      These findings support further testing of the clinical value of parenteral,
      adjusted, high-dose UH in patients with acute stroke.

PMID- 15264227
TI  - Antisense peptide nucleic acid targeting GluR3 delays disease onset and
      progression in the SOD1 G93A mouse model of familial ALS.
AB  - Glutamate excitotoxicity is strongly implicated as a major contributing factor in
      motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Excitotoxicity
      results from elevated intracellular calcium ion (Ca(2+)) levels, which in turn
      recruit cell death signaling pathways. Recent evidence suggests that alpha-amino
      3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit (GluR)
      stoichiometry is a dominant factor leading to excess Ca(2+) loading in
      neurodegeneration. In particular, the Ca(2+) permeable glutamate receptor subunit
      3 (GluR3) has been implicated in several neurologic conditions such as bipolar
      disorder and epilepsy. Recent proteomic analysis within our group on the copper
      zinc superoxide dismutase (SOD1)(G93A) transgenic mouse model of familial ALS
      (FALS) reveals a potentially deleterious upregulation of GluR3 in spinal cord
      compared to that in wild-type littermates. Based on this finding we designed a
      12mer antisense peptide nucleic acid (PNA) directed against GluR3. This sequence
      significantly reduced levels of GluR3 protein and protected neuroblastoma x
      spinal cord (NSC-34) cells against death induced by the AMPA receptor-specific
      agonist (S)-5-fluorowillardiine. We subsequently treated SOD1(G93A) mice thrice
      weekly with intraperitoneal injections of the antisense PNA (2.5 mg/kg)
      commencing at postnatal day 50. Mice treated with the antisense sequence had
      significantly extended survival compared to mice injected with a nonsense
      sequence. Western blot analysis, however, did not reveal a significant reduction
      in GluR3 protein levels in whole extracts of the lumbar spinal cord. These
      results suggest that interference with the GluR3 component of the AMPA receptor
      assembly may be a novel strategy for controlling excitotoxic destruction of motor
      neurons and may lead to new therapeutic opportunities for the treatment of human
      ALS.

PMID- 15264228
TI  - Cytotoxic mechanisms by M239V presenilin 2, a little-analyzed Alzheimer's disease
      causative mutant.
AB  - Although neurotoxic functions are well characterized in familial Alzheimer's
      disease (FAD)-linked N141I mutant of presenilin (PS)2, little has been known
      about M239V-PS2, another established FAD-causative mutant. We found that
      expression of M239V-PS2 caused neuronal cytotoxicity. M239V-PS2 exerted three
      forms of cytotoxicity: one was sensitive to both an antioxidant glutathione-ethyl
      ester (GEE) and a caspase inhibitor Ac-DEVD-CHO (DEVD); the second was sensitive
      to GEE but resistant to DEVD; and the third was resistant to both. The GEE/DEVD
      sensitive cytotoxicity by M239V-PS2 was likely through NADPH oxidase and the GEE
      sensitive/DEVD-resistant cytotoxicity through xanthine oxidase (XO). Both
      mechanisms by M239V-PS2 were suppressed by pertussis toxin (PTX) and were
      mediated by Galpha(o), but not by Galpha(i). Although Abeta1-43 itself induced no
      cytotoxicity, Abeta1-43 potentiated all three components of M239V-PS2
      cytotoxicity. As these cytotoxic mechanisms by M239V-PS2 are fully shared with
      N141I-PS2, they are most likely implicated in the pathomechanism of FAD by PS2
      mutations. Notably, cytotoxicity by M239V-PS2 could be inhibited by the
      combination of two clinically usable inhibitors of superoxide-generating enzymes,
      apocynin and oxypurinol.

PMID- 15264229
TI  - Food deprivation decreases responsiveness of ventromedial hypothalamic neurons to
      melanocortins.
AB  - The melanocortin system is involved in regulation of food intake and energy
      balance. Melanocyte-stimulating hormone (alpha-MSH) is an endogenous melanocortin
      receptor (MC-R) agonist. It acts on MC3/4 receptors to reduce appetite and to
      increase energy expenditure. The production of alpha-MSH is reduced during food
      deprivation, but MC4-R density is increased. The net effect of reduced alpha-MSH
      production and increased receptor level is not clear. To address this question,
      responses of ventromedial hypothalamic (VMH) neurons to melanotan II (MTII; a
      synthetic analogue of alpha-MSH) were recorded in brain slices from fed and food
      deprived rats. Responses to the highest dose MTII were observed in 61% of VMH
      neurons from fed rats but only 33% of VMH neurons from food-deprived rats. To
      assess a possible mechanism by which responsiveness to melanocortins is
      diminished even though receptor number is augmented during fasting, we examined
      the effect of agouti gene-related peptide (AGRP), an endogenous MC-R antagonist
      that stimulates food intake. The synthesis of AGRP increases during fasting. AGRP
      significantly reduced VMH responsiveness to MTII. Additionally, AGRP by itself
      evoked neuronal responses, in contrast to synthetic MC-R antagonists. AGRP (1 nM)
      induced a predominant inhibitory effect on VMH neurons in food-deprived rats but
      not in fed rats. In the presence of AGRP, MTII induced a significant inhibition
      of neuronal activity in deprived rats, but not in fed rats. Inhibition of VMH
      neurons reduces energy expenditure and the satiety signal. These findings suggest
      that although food deprivation increases MC4-R density, it nevertheless reduces
      the effectiveness of melanocortins on VMH neurons, possibly by the involvement of
      AGRP.

PMID- 15264230
TI  - Effects of unilateral vestibular ganglionectomy on glutaminase activity in the
      vestibular nerve root and vestibular nuclear complex of the rat.
AB  - The metabolism of glutamate, the most likely neurotransmitter of vestibular
      ganglion cells, includes synthesis from glutamine by the enzyme glutaminase. We
      used microdissection combined with a fluorometric assay to measure glutaminase
      activity in the vestibular nerve root and nuclei of rats with unilateral
      vestibular ganglionectomy. Glutaminase activity in the lesioned-side vestibular
      nerve root decreased by 62% at 4 days after ganglionectomy and remained at
      similar values through 30 days. No change occurred in the contralateral
      vestibular nerve root. Glutaminase activity changes in the vestibular nuclei were
      lesser in magnitude and more complex, including contralateral increases as well
      as ipsilateral decreases. At 4 days after ganglionectomy, glutaminase activity
      was 10-20% lower in individual lesioned-side nuclei compared with their
      contralateral counterparts. By 14 and 30 days after ganglionectomy, there were no
      statistically significant differences between the nuclei on the two sides. This
      transient asymmetry of glutaminase activities in the vestibular nuclei contrasts
      with the sustained asymmetry in the vestibular nerve root and suggests that
      intrinsic, commissural, or descending pathways are involved in the recovery of
      chemical symmetry. This recovery resembles our previous finding for glutamate
      concentrations in the vestibular nuclei and may partially underlie central
      vestibular compensation after peripheral lesions.

PMID- 15264231
TI  - Pressor effects of electrical stimulation of medial prefrontal cortex in
      unanesthetized rats.
AB  - The medial prefrontal cortex (MPFC) is involved in central nervous system (CNS)
      mediated cardiovascular modulation. We compared the cardiovascular effects of
      electrical stimulation (EE) of the MPFC in unanesthetized rats to those observed
      after stimulation of the same area in urethane-anesthetized rats. Electrical
      stimulation (35, 106, 177, 247, 318, and 389 microA rms/10 sec, 60-Hz sine wave)
      of the MPFC of urethane-anesthetized rats caused depressor responses of stimulus
      related intensity. The cardiovascular response to electrical stimulation of the
      MPFC in unanesthetized rats was characterized by stimulus-related pressor
      responses. No significant heart rate changes were observed during the EE period
      in any case. The pressor response to electrical stimulation (106 microA rms/10
      sec, 60-Hz sine wave) of the MPFC was not affected by intravenous pretreatment
      with the vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 microg/kg,
      intravenously), by hypophysectomy, or by intravenous pretreatment with the
      angiotensin II antagonist losartan (1 mg/kg, intravenously). The pressor response
      was blocked by intravenous pretreatment with the ganglionic blocker mecamylamine
      (2 mg/kg, intravenously) but was not affected by adrenal demedullation, thus
      suggesting involvement of the neural component of the sympathetic nervous system
      without a major involvement of its hormonal component. Our results confirmed the
      occurrence of depressor responses after electrical stimulation of the MPFC in
      urethane-anesthetized rats and evidenced that only pressor responses are observed
      after its stimulation in unanesthetized rats. The fact that the pressor response
      to the stimulation of the MPFC was blocked by a ganglioplegic suggests that the
      MPFC has functional excitatory actions over the sympathetic nervous system.

PMID- 15264232
TI  - Contribution of electrospray mass spectrometry for the characterization, design,
      and development of nitrido technetium and rhenium heterocomplexes as potential
      radiopharmaceuticals.
AB  - Diagnostic nuclear medicine (NM) is among the imaging procedures (together with X
      ray, computerized tomography, magnetic resonance, and echography) the clinicians
      can routinely adopt to image organs or tissues and related disorders. (99m)Tc
      based agents are the radiopharmaceuticals of election in diagnostic NM because of
      the ideal physical properties of the 99mTc nuclide (t1/2 6.01 hr; Egamma 142
      keV), low cost, and easy availability through the commercial 99Mo/99mTc
      generator, and chemical versatility of the element. In the last two decades the
      synergistic work of clinics, pharmacologists, and coordination chemists has had a
      tremendous impact in the development of new 99mTc-based radiopharmaceuticals
      through the recognition of the structure at the molecular level of the agent
      utilized. This has been achieved by studying the physico-chemical properties of
      the long-lived 99gTc (t1/2 2.11 x 10(5) year; Ebeta 292 keV) and third-row
      congener Re isostructural compounds. Electrospray ionization mass spectrometry
      (ESI-MS) and collision experiments (MS/MS) represent valuable analytical
      techniques suitable for the characterization of both technetium and rhenium
      complexes relevant to NM. Unequivocal structural identification of these
      bioinorganic compounds, either simple coordination complexes ("essential
      radiopharmaceuticals") or more sophisticated structures carrying bioactive
      fragments ("receptor-specific" radiopharmaceuticals), can be realized in
      combination with multinuclear NMR spectroscopy. MS/MS experiments provide useful
      information on the different metal-ligand bond strength, and comparison of the
      fragmentation profiles of isostructural technetium and rhenium compounds give
      additional details on the role played by the metal in determining preferred
      decomposition channels. The analysis of these data contribute to design novel
      synthetic strategies for the obtainment of technetium and rhenium compounds
      relevant to NM. The chemistry underlying the production of a new class of
      potential radiopharmaceuticals including a terminal nitrogen bond and a mixed
      coordination sphere comprising heterodiphosphines and/or dithiocarbamates (DTC)
      is presented in detail together with the ESI-MS and MS/MS investigations.

PMID- 15264233
TI  - Proteome analysis of apoptotic cells.
AB  - Apoptosis, a genetically determined form of cell death, is a central and complex
      process involved in the development of multicellular organisms in the maintenance
      of cell homeostasis. During apoptosis, a large number of proteins involved in
      transducing signals are posttranslationally modified. Classical proteomics, the
      combination of protein separation by two-dimensional gel electrophoresis (2DGE)
      and protein identification by mass spectrometry (MS), enabled the discovery of
      more than 100 proteins altered during apoptosis. Functional data about protein
      degradation, modification, translocation, and synthesis were obtained. In
      addition to classical proteomics, some specifically designed proteome studies
      were carried out to analyze specific apoptotic components such as the
      mitochondrial releasing factors, death-inducing signaling complex (DISC),
      inhibitor of apoptosis (IAP) interacting proteins, and caspases. The
      identification of main regulators significantly influenced the elucidation of the
      concept underlying apoptosis signaling. Thus, the application of detailed protein
      analytical methods in the young field of apoptosis research was particularly
      fruitful.

PMID- 15264234
TI  - Studying the interactome with the yeast two-hybrid system and mass spectrometry.
AB  - Protein interactions are crucial to the life of a cell. The analysis of such
      interactions is allowing biologists to determine the function of uncharacterized
      proteins and the genes that encode them. The yeast two-hybrid system has become
      one of the most popular and powerful tools to study protein-protein interactions.
      With the advent of proteomics, the two-hybrid system has found a niche in
      interactome mapping. However, it is clear that only by combining two-hybrid data
      with that from complementary approaches such as mass spectrometry (MS) can the
      interactome be analyzed in full. This review introduces the yeast two-hybrid
      system to those unfamiliar with the technique, and discusses how it can be used
      in combination with MS to unravel the network of protein interactions that occur
      in a cell.

PMID- 15264235
TI  - Investigation of intact protein complexes by mass spectrometry.
AB  - Mass spectrometry has grown in recent years to a well-accepted and increasingly
      important complementary technique in structural biology. Especially electrospray
      ionization mass spectrometry is well suited for the detection of non-covalent
      protein complexes and their interactions with DNA, RNA, ligands, and cofactors.
      Over the last decade, significant advances have been made in the ionization and
      mass analysis techniques, which makes the investigation of even larger and more
      heterogeneous intact assemblies feasible. These technological developments have
      paved the way to study intact non-covalent protein-protein interactions, assembly
      and disassembly in real time, subunit exchange, cooperativity effects, and
      effects of cofactors, allowing us a better understanding of proteins in cellular
      processes. In this review, we describe some of the latest developments and
      several highlights.

PMID- 15264237
TI  - Identification of polycomb group protein enhancer of zeste homolog 2 (EZH2)
      derived peptides immunogenic in HLA-A24+ prostate cancer patients.
AB  - BACKGROUND: Antigens overexpressed in metastatic prostate cancer are appropriate
      targets in anti-cancer immunotherapy, and one candidate is the polycomb group
      protein enhancer of zeste homolog 2 (EZH2). METHODS: Eleven EZH2-derived peptides
      were prepared based on the HLA-A24 binding motif. These peptide candidates were
      screened first by their ability to be recognized by immunoglobulin G (IgG), and
      then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs).
      RESULTS: IgGs reactive to three EZH2 peptides (EZH2-243 to -252, EZH2-291 to 
      299, and EZH2-735 to -;742) were detected in the plasma of almost half of
      prostate cancer patients. Among them, the EZH2-291 to -299 and EZH2-735 to -742
      peptides effectively induced HLA-A24-restricted and prostate cancer-reactive CTLs
      from prostate cancer patients. The cytotoxicity was mainly dependent on EZH2
      peptide-specific and CD8+ T cells. CONCLUSIONS: These EZH2-291 to -299 and EZH2
      735 to -742 peptides could be promising candidates for peptide-based
      immunotherapy for HLA-A24+ prostate cancer patients with metastases.

PMID- 15264238
TI  - Application of serum PSA to identify acute bacterial prostatitis in patients with
      fever of unknown origin or symptoms of acute pyelonephritis.
AB  - BACKGROUND: Exclusion of prostatitis in screening for prostate cancer (Cap) is a
      matter of concern in the prostate-specific antigen (PSA) era. Yet, the
      identification of acute bacterial prostatitis (ABP), intentionally utilizing PSA
      in patients with pyrexia has been scarcely reported. METHODS: In total, 39 men,
      who presented at our department with a fever higher than 38.3 degrees C, were
      randomly selected. We investigated the fraction of patients who had serum PSA
      levels higher than 4.0 ng/ml and categorized them according to an initial
      diagnosis of pyelonephritis, ABP, other urogenital infections, and fever of
      unknown origin (FUO). RESULTS: Six of nine cases initially diagnosed as
      pyelonephritis, presented with elevated PSA levels between 9.5 and 75.1 ng/ml.
      All six cases of clinically diagnosed prostatitis had PSA elevated between 4.1
      and 13.6 ng/ml. In 8 of 18 FUO cases, PSA was elevated between 5.1 and 77.0
      ng/ml. PSA levels significantly correlated with age (P < 0.005). All 20 patients
      with elevated PSA received antibiotics, and serum PSA was significantly reduced
      in all cases (P < 0.001) together with the alleviation of fever and normalization
      of CRP. CONCLUSIONS: PSA is a prompt and steady diagnostic tool for identifying
      ABP that might be missed or misdiagnosed. We recommend the measurement of PSA in
      cases not only with urologic infection but also puzzling pyrexia.

PMID- 15264239
TI  - Can color doppler predict the uniformity of HIFU-induced prostate tissue
      destruction?
AB  - BACKGROUND: Tissue blood perfusion influences the results of some hyperthermia
      and thermotherapy procedures, but its role in the outcome of prostate cancer
      treatment by high-intensity focused ultrasound (HIFU) has not been evaluated yet.
      We evaluated preoperative prostate color Doppler as a predictor of the efficacy
      of HIFU treatment. METHODS: Thirty-five patients underwent pre- and post-contrast
      color Doppler examination of the prostate before HIFU treatment. Specific
      software was used to calculate, on color Doppler images, the color pixel density
      (CPD), and the specific flow (SF, i.e., mean velocity x CPD) in different regions
      of interest. Post-treatment sextant biopsies were obtained in 31 patients, 5.8 +/
      2.8 months after HIFU treatment. RESULTS: No significant correlation was found
      between the uniformity of HIFU-induced tissue destruction observed on control
      biopsies and the pre-treatment CPD/SF values in any region of interest, either
      before or after contrast injection. On the other hand, history of radiation
      therapy was significantly associated with homogeneous tissue destruction and
      history of hormone therapy was significantly associated with incomplete tissue
      destruction. CONCLUSIONS: Color Doppler cannot predict the uniformity of HIFU
      induced tissue destruction. History of radiation therapy was found to be a factor
      of favorable prognosis and history of hormone therapy was found to be a factor of
      poor prognosis in our population.

PMID- 15264240
TI  - Mutational analysis of PINX1 in hereditary prostate cancer.
AB  - BACKGROUND: Telomerase activity is increased in most tumors. PinX1 has recently
      been identified as a critical component in regulating telomerase activity. The
      PinX1 gene is located within chromosomal region 8p22-23, a region associated with
      LOH and potentially linked to increased prostate cancer risk. METHODS: PINX1 was
      re-sequenced in 159 hereditary prostate cancer (HPC) probands. Four non
      synonymous coding variants were genotyped in 159 HPC families. RESULTS: Thirty
      nine polymorphisms were identified in the HPC screening panel. Ten coding
      polymorphisms were identified, seven (Gln50His, Leu91Met, Gln206His, Arg215Ile,
      Thr220Ala, Ser254Cys, and Glu414Ala) of which were non-synonymous. The most
      common variants Thr220Ala and Ser254Cys were not significantly over-transmitted
      from affected parent to affected offspring. CONCLUSIONS: Based on these results,
      we conclude that PINX1 is not a major factor for HPC risk.

PMID- 15264241
TI  - RNA interference targeting Stat3 inhibits growth and induces apoptosis of human
      prostate cancer cells.
AB  - Stat3, a member of the signal transduction and activation of transcription (STAT)
      family, is a key signal transduction protein that mediates signaling by
      cytokines, peptide growth factors, and oncoproteins and is constitutively
      activated in numerous cancers including prostate. Previous studies demonstrated
      that constitutively activated Stat3 plays an important role in the development
      and progression of prostate cancer by promoting cell proliferation and protecting
      against apoptosis. The present study was designed to investigate the potential
      use of RNA interference to block Stat3 expression and activation and the effect
      on the growth of human prostate cancer cells. We identified a small interfering
      RNA (siRNA) specific for Stat3 and demonstrate that blockade of Stat3 activation
      by the Stat3 siRNA suppresses the growth of human prostate cancer cells and Stat3
      mediated gene expression and induces apoptotic cell death. The Stat3 siRNA does
      not inhibit the proliferation nor induces apoptosis of Stat3-inactive human
      prostate cancer cells. In addition, the Stat3 siRNA inhibits the levels of
      androgen-regulated prostate specific antigen (PSA) expression in prostate cancer
      cells. These results demonstrate that targeting Stat3 signaling using siRNA
      technique may serve as a novel therapeutic strategy for treatment of prostate
      cancer expressing constitutively activated Stat3.

PMID- 15264242
TI  - The effect of combined androgen ablation on the expression of alpha1A-adrenergic
      receptor in the human prostate.
AB  - BACKGROUND: This study was designed to determine whether androgen ablation (AA)
      affects expression of alpha1A-adrenergic receptors (AR) in the human prostate.
      METHODS: Concentrations of alpha1A-AR mRNA were determined in benign prostatic
      tissue from patients undergoing surgery after a 3-month course of combined
      androgen ablation (CAD) therapy with leuprolide and flutamide, and a matched
      group of untreated patients with clinical BPH. RESULTS: Mean concentration of
      alpha1A-AR in the AA group was 0.53 +/- 0.53 SD (range 0.026-1.55) attomol/mg.
      Control mean was 0.29 +/- 0.22 SD (range 0.02-0.69; P = 0.3, two tailed t-test).
      Tissue composition did not statistically differ between the two groups.
      Expression of alpha1A-AR correlated with concentration of smooth muscle myosin
      heavy chain (SMMHC) (r = 0.84, P = 0.001). No significant differences were
      observed after adjusting for SMMHC content. CONCLUSIONS: A 3-month course of CAD
      does not appear to have a significant effect on alpha1A-AR mRNA expression in the
      human prostate.

PMID- 15264243
TI  - Targeting the HGF/SF receptor c-met using a hammerhead ribozyme transgene reduces
      in vitro invasion and migration in prostate cancer cells.
AB  - BACKGROUND: Hepatocyte growth factor scatter factor (HGF/SF) elicits a number of
      biological activities including invasion and migration through activation of its
      tyrosine kinase receptor c-Met. Over expression of c-Met has been implicated in
      prostate cancer development and progression. This study examined the effect of a
      ribozyme transgene, designed to inhibit human c-Met expression, and its impact on
      in vitro invasion and migration in prostate cancer. METHODS: A transgene (Met
      560) consisting of U1 snRNA, hammerhead ribozyme, and antisense was cloned into a
      modified pZeoU1-EcoSpe vector and transfected into DU-145 cells. The effect of
      HGF/SF was tested on prostate cancer cells whose expression of c-Met had been
      blocked by way of a ribozyme transgene. RESULTS: Met 560 stable transfectants (DU
      145(+/+)) manifested a complete loss of c-Met expression at mRNA and protein
      levels. In contrast, control plasmid (DU-145(+/-)) and wild-type DU-145 cells (DU
      145(-/-)) had similar levels of c-Met expression. HGF/SF significantly increased
      the in vitro invasiveness (mean 47.71 +/- SE 7.75; P < 0.01 vs. control 24.14 +/-
      1.34), and migration (mean 48.44 +/- SE 3.51; P < 0.01 vs. control 22.95 +/-
      1.47) of DU-145(-/-) cells, respectively. Similarly, HGF/SF also increased the
      invasion (62.33 +/- 6.34; P < 0.001 vs. control 24.5 +/- 2.35) and migration
      (46.14 +/- 2.26; P < 0.01 vs. control 21.82 +/- 1.62) of DU-145(+/-) cells. In
      contrast, DU-145(+/+) cells had lost its response to HGF/SF induced invasion
      (22.33 +/- 2.08; P > 0.05 vs. control 23.5 +/- 2.11) and migration (24.12 +/-
      0.86; P > 0.05 vs. control 23.27 +/- 0.81). CONCLUSIONS: Targeting the HGF/SF
      receptor by way of a hammerhead ribozyme encoding antisense to c-Met, is an
      effective method to reduce the invasive or migration potential in prostate
      cancer, and may have important therapeutic implications.

PMID- 15264244
TI  - Proteomic analysis of dunning prostate cancer cell lines with variable metastatic
      potential using SELDI-TOF.
AB  - BACKGROUND: Surface enhanced laser desorption and ionization-time-of-flight
      (SELDI-TOF) is an evolving proteomic technology for improving biomarker discovery
      that allows for rapid and sensitive analysis of complex protein mixtures
      generated from body fluids, cells, and/or tissues. SELDI--based profiling
      identifies unique, differentially expressed proteins relating to specific cancer
      related disease states. We utilized SELDI-TOF following pre-processing with
      molecular separation and chemical fractionation of cell membrane extracts from
      three Dunning rat prostate cancer cell lines of varying metastatic potential to
      search novel proteins that are differentially expressed. METHODS: Dunning rat
      cell sublines of variable (%) metastatic potential; G (0%), AT-1 (20%), and Mat
      Ly-Lu (100%) were cultured in two different laboratories. Cell lysis was
      performed in a homogenation buffer (320 mM sucrose/50 mM Tris/0.5 mM PSMF) using
      Dounce homogenation. After centrifugation, the membrane pellet was washed 2x and
      then solublized in 2% CHAPS/8 M urea. This sample was further processed using
      positive pressure molecular ultrafiltration at 30 kDa or precipitation with 50%
      ammonium sulfate. Next, each sample was applied to an IMAC3-Ni ProteinChip
      (Ciphergen Biosystems, Freemont, CA) and analyzed using Ciphergen's Protein
      Biology System with protein peak analysis software. RESULTS: SELDI-TOF analysis
      differentiated the three Dunning rat cell sublines based upon protein
      concentration normalized profiles between 5,000 and 20,000 Da. The preparations
      from the three cells lines showed clear differences when the extracts from the
      metastatic sublines (AT-1 and MLL) were compared to the benign subline (G) for
      proteins with molecular weights of 9 kDa (decrease), 12 kDa (significant
      decrease), 14 kDa (decrease), and 17 kDa (significant gain). After pre-processing
      extracts with ammonium sulfate and molecular ultrafiltration, the molecular
      profile changes from one subline to the next became more apparent. Our results
      were reproducible using multiple runs including from Dunning cells cultured in a
      separate laboratory, and using different lots of SELDI ProteinChips. CONCLUSIONS:
      The application of SELDI-TOF to a series of Dunning rat prostate cancer cell
      lines illustrated apparent changes in protein profiles among the three cell lines
      with known differences in metastatic biologic activity. SELDI-TOF identified four
      reproducible changes in protein expression in the AT1 and MLL metastatic cell
      sublines. Three of the expression changes were manifested as decreases, but one
      protein (17 kDa) was over-expressed in the AT1 and MLL cell lines. Emphasis will
      be placed on the isolation, purification, and characterization of the 17 kDa over
      expressed protein and its potential role in PCa metastasis.

PMID- 15264246
TI  - Thromboprophylaxis for radical prostatectomy: a comparative analysis of present
      practice between the USA, the UK, and Ireland.
AB  - BACKGROUND: A clinical dilemma exists in the management of patients undergoing
      radical prostatectomy (RP) whereby measures taken to reduce the risk of
      thrombotic events may adversely affect efforts to limit blood loss. No consensus
      exists in the literature on the ideal management of thromboprophylaxis in these
      patients. Our aim is to examine and compare current thromboprophylactic policy
      and practice between the centres involved in performing RP. METHODS: A
      questionnaire was forwarded to all urology residency programmes in Ireland, the
      United Kingdom, and the United States, regarding their current practice with
      respect to thromboprophylaxis in RP. Completed questionnaire were returned by fax
      and the data entered into a computer database. RESULTS: An overall response rate
      of 60% was achieved. The questionnaires demonstrated a significant difference in
      clinical practice between Urologists in the United States and the United Kingdom.
      Just 24% of American Urologists use pharmacological thromboprophylaxis in
      contrast to 100% of British Urologists. There was no difference in the use of non
      pharmacological thromboprophylaxis. Pharmacological thromboprophylaxis is mainly
      administered by units, mostly in the United Kingdom, doing fewer radical
      prostatectomies. CONCLUSIONS: While there have been studies advocating the use of
      pharmacological thromboprophylaxis in patients undergoing major pelvic surgery,
      there is no consensus on it is use in urological practice. This study has
      demonstrated significant differences in the management of thromboprophylaxis
      between the USA and the UK/Ireland. Units performing the largest number of
      radical prostatectomies, mostly in the USA, do not use pharmacological
      thromboprophylaxis and most do not use compression boots.

PMID- 15264245
TI  - The use of trastuzumab in the treatment of hormone refractory prostate cancer;
      phase II trial.
AB  - PURPOSE: To investigate the efficacy and toxicity of the antibody to the HER
      2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone
      refractory prostate cancer (HRPC). MATERIALS AND METHODS: Eighteen patients with
      HRPC were recruited for this phase II trial in which they received trastuzumab
      for 12 weeks or until disease progression or unacceptable toxicity was
      documented. HER-2 receptor overexpression was evaluated using
      immunohistochemistry (IHC) and dual-color fluorescence in-situ hybridization
      (FISH) assays. RESULTS: Trastuzumab as a single agent demonstrated little
      efficacy in treating HRPC. Two patients demonstrated stable disease based on a
      decrease in PSA level to less than 50% of baseline. No patient demonstrated a
      regression of radiographic bony or soft tissue metastatic disease. The medication
      was well tolerated in 16 patients (89%), and 2 patients (11%) had to be
      hospitalized for cardiac complications. CONCLUSIONS: Trastuzumab (Herceptin) as a
      single agent demonstrated poor efficacy in treating HRPC. Based on promising
      results in treating breast cancer with regimens using Herceptin and cytotoxic
      agents, a similar combination approach might demonstrate better efficacy in
      treating HRPC.

PMID- 15264247
TI  - Androgen receptor polymorphisms and risk of biochemical failure among
      prostatectomy patients.
AB  - BACKGROUND: Little is known about the role of inherited genotypes in prostate
      cancer (PC) progression. This prospective study evaluated the predictive value of
      androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy
      patients. METHODS: We studied 354 patients registered at M. D. Anderson Cancer
      Center from 1991 to 2001. Kaplan-Meier and Cox proportional hazard analyses were
      used. RESULTS: During an average follow-up of 56 months, 66 (19%) post
      prostatectomy patients experienced biochemical failure (BF). Patients with higher
      CAG repeats (CAG > or = 24) had significantly longer BF-free survival (BFFS) than
      those with fewer repeats (CAG < or = 23) (P = 0.04). Higher CAG repeats were
      significantly associated with lower BF risk among Whites and African Americans.
      Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and
      Gleason score > or = 8 (RR = 19.33, P = 0.005) remained significant BFFS
      predictors in multivariate analysis. GGC repeats were not associated with BF.
      CONCLUSIONS: Our data showed that an inherited polymorphism (CAG repeats) in the
      AR is related to differences in genetic susceptibility to BF, supporting the
      hypothesis that increased AR activity may play a role in PC progression.

PMID- 15264248
TI  - PC-3 cells with enhanced androgen receptor signaling: a model for clonal
      selection in prostate cancer.
AB  - BACKGROUND: Two sublines of the human prostate cancer cell line, PC-3, which is
      widely used as a model of prostate cancer progression, have been reported: PC
      3(AR-) that do not express androgen receptor (AR), and PC-3AR+ that have
      measurable AR RNA but little protein. METHODS: We assayed the geneotype,
      karyotype, AR expression, and physical characteristics of the two PC-3 sublines,
      and compared their ability to elicit a transactivation response from ectopic AR
      in the presence and absence of specific AR coregulators. RESULTS: PC-3(AR-) and
      PC-3AR+ cells are genotypically and karyotypically similar, but exhibit salient
      differences in their morphology, growth rate, and expression of AR RNA. Whereas
      endogenous AR expression in PC-3AR+ cells does not result in sufficient protein
      to confer androgen responsiveness in culture, ectopic AR consistently elicited a
      much greater transactivation response in PC-3AR+ than in PC-3(AR-) cells, without
      altered sensitivity to activation by native ligand or AR coregulators including
      GRIP1, BRCA1, and Zac1. Moreover, phenotypic differences of AR variants
      implicated in prostate cancer susceptibility and progression were only observed
      in PC-3AR+ cells. Higher levels of known AR coregulator proteins detected in PC
      3AR+ compared with PC-3(AR-) cells likely contribute to these differences.
      CONCLUSIONS: These studies provide new evidence that the androgen-signaling axis
      can be sensitized in prostate cancer cells, and have important implications for
      the analysis and interpretation of AR structure and function in in vitro cell
      systems.

PMID- 15264250
TI  - Models for the treatment of crystalline solids and surfaces.
AB  - Crystalline solids and surfaces have become a subject of growing interest. The
      difficulty of a comprehensive description of a variety of phenomena by a single
      method has led to the development of many models. These models can be classified
      as nonperiodic and periodic models. The former include free clusters, saturated
      clusters, and embedded clusters. The latter two models serve to remove the
      boundary effects of the free clusters. No perfect avoidance of such effects can
      be achieved in this way. The cyclic cluster model overcomes this difficulty in a
      natural way. It is periodic with a finite periodicity. An embedding can take into
      account a long-range effect in ionic crystals. Previous periodic approaches
      relied on the large unit cell model, which is related to the supercell approach.
      For perfect crystals the conventional unit cell approach is a well-known
      standard. However, its disadvantage is the unphysical periodicity of defects,
      which is avoided in the cyclic cluster model. The present article presents a
      description of these models together with selective applications to solid-state
      systems and surfaces.

PMID- 15264249
TI  - Pim-1 expression in prostatic intraepithelial neoplasia and human prostate
      cancer.
AB  - BACKGROUND: PIM-1, an oncogene product of serine/threonine kinase, has been found
      to play an important role in induction/suppression of apoptosis, cell cycle
      progression, and transcriptional regulation by phosphorylating the target
      proteins involved in these processes. Recently, the expression of PIM-1 has been
      shown to correlate significantly with measures of prostate cancer clinical
      outcome. METHODS: Immunohistochemical analysis was used to characterize the
      patterns of PIM-1 expression in high grade prostatic intraepithelial neoplasia
      (HGPIN) and cancer in 121 radical prostatectomy specimens. RESULTS: Moderate to
      strong cytoplasmic staining was observed in 68% of cancers, 12% presented nuclear
      positivity as well. Moderate to strong expression was seen in 76% of tumors with
      Gleason score (GS) 7 or higher compared to 58% in tumors with GS 6 or lower (P =
      0.04). The staining intensity was moderate or strong in 97% of HGPIN lesions. PIM
      1 was overexpressed in HGPIN compared to cancer in 65% of cases. Expression in
      benign glands was negative or only weakly positive. CONCLUSION: Our data suggest
      that PIM-1 overexpression in HGPIN may be an early event in the development of
      prostate malignancy. Additionally, PIM-1 expression provides supplementary
      information for distinguishing HGPIN from benign epithelium.

PMID- 15264251
TI  - Fluctuation analysis and accuracy of a large-scale in silico screen.
AB  - Using a cascadic version of the stochastic tunneling method we perform an all
      atom database screen over 186,000 flexible ligands of the NCI 3D database against
      the thymidine kinase receptor. By analyzing the errors in the binding energy we
      demonstrate how the cascadic technique is superior to conventional sequential
      docking techniques and how reliable results for the determination of the top
      scoring ligands could be achieved. The substrate corresponding to the crystal
      structure used in the screen ranks in the upper 0.05% of the database, validating
      both docking methodology and the applicability of the scoring function to this
      substrate. Several high ranking ligands of the database display significant
      structural similarity with known substrates. A detailed analysis of the accuracy
      of the screening method is carried out, and its dependence on the flexibility of
      the ligand is quantified.

PMID- 15264252
TI  - Structure and dynamics of the CrIII ion in aqueous solution: Ab initio QM/MM
      molecular dynamics simulation.
AB  - Structural and dynamical properties of the Cr(III) ion in aqueous solution have
      been investigated using a combined ab initio quantum mechanical/molecular
      mechanical (QM/MM) molecular dynamics simulation. The hydration structure of
      Cr(III) was determined in terms of radial distribution functions, coordination
      numbers, and angular distributions. The QM/MM simulation gives coordination
      numbers of 6 and 15.4 for the first and second hydration shell, respectively. The
      first hydration shell is kinetically very inert but by no means rigid and
      variations of the first hydration shell geometry lead to distinct splitting in
      the vibrational spectra of Cr(H(2)O)(6) (3+). A mean residence time of 22 ps was
      obtained for water ligands residing in the second hydration shell, which is
      remarkably shorter than the experimentally estimated value. The hydration energy
      of -1108 +/- 7 kcal/mol, obtained from the QM/MM simulation, corresponds well to
      the experimental hydration enthalpy value.

PMID- 15264253
TI  - Empirical force fields for biological macromolecules: overview and issues.
AB  - Empirical force field-based studies of biological macromolecules are becoming a
      common tool for investigating their structure-activity relationships at an atomic
      level of detail. Such studies facilitate interpretation of experimental data and
      allow for information not readily accessible to experimental methods to be
      obtained. A large part of the success of empirical force field-based methods is
      the quality of the force fields combined with the algorithmic advances that allow
      for more accurate reproduction of experimental observables. Presented is an
      overview of the issues associated with the development and application of
      empirical force fields to biomolecular systems. This is followed by a summary of
      the force fields commonly applied to the different classes of biomolecules;
      proteins, nucleic acids, lipids, and carbohydrates. In addition, issues
      associated with computational studies on "heterogeneous" biomolecular systems and
      the transferability of force fields to a wide range of organic molecules of
      pharmacological interest are discussed.

PMID- 15264254
TI  - UCSF Chimera--a visualization system for exploratory research and analysis.
AB  - The design, implementation, and capabilities of an extensible visualization
      system, UCSF Chimera, are discussed. Chimera is segmented into a core that
      provides basic services and visualization, and extensions that provide most
      higher level functionality. This architecture ensures that the extension
      mechanism satisfies the demands of outside developers who wish to incorporate new
      features. Two unusual extensions are presented: Multiscale, which adds the
      ability to visualize large-scale molecular assemblies such as viral coats, and
      Collaboratory, which allows researchers to share a Chimera session interactively
      despite being at separate locales. Other extensions include Multalign Viewer, for
      showing multiple sequence alignments and associated structures; ViewDock, for
      screening docked ligand orientations; Movie, for replaying molecular dynamics
      trajectories; and Volume Viewer, for display and analysis of volumetric data. A
      discussion of the usage of Chimera in real-world situations is given, along with
      anticipated future directions. Chimera includes full user documentation, is free
      to academic and nonprofit users, and is available for Microsoft Windows, Linux,
      Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from
      http://www.cgl.ucsf.edu/chimera/.

PMID- 15264255
TI  - Classical force field parameters for the heme prosthetic group of cytochrome c.
AB  - Accurate force fields are essential for describing biological systems in a
      molecular dynamics simulation. To analyze the docking of the small redox protein
      cytochrome c (cyt c) requires simulation parameters for the heme in both the
      reduced and oxidized states. This work presents parameters for the partial
      charges and geometries for the heme in both redox states with ligands appropriate
      to cyt c. The parameters are based on both protein X-ray structures and ab initio
      density functional theory (DFT) geometry optimizations at the B3LYP/6-31G* level.
      The simulations with the new parameter set reproduce the geometries of the X-ray
      structures and the interaction energies between water and heme prosthetic group
      obtained from B3LYP/6-31G* calculations. The parameter set developed here will
      provide new insights into docking processes of heme containing redox proteins.

PMID- 15264256
TI  - Solvation forces on biomolecular structures: a comparison of explicit solvent and
      Poisson-Boltzmann models.
AB  - Continuum electrostatics methods have become increasingly popular due to their
      ability to provide approximate descriptions of solvation energies and forces
      without expensive sampling required by explicit solvent models. In particular,
      the Poisson-Boltzmann equation (PBE) provides electrostatic potentials, solvation
      energies, and forces by modeling the solvent as a featureless, dielectric
      material, and the mobile ions as a continuous distribution of charge. Polar
      solvation forces and energies obtained from the PBE are often supplemented with
      simple solvent-accessible surface area (SASA) models of nonpolar solvation. Given
      the recent development of methods that enable the use of PBE and SASA forces in
      molecular dynamics simulations, it is important to determine the ability of these
      implicit solvent models to accurately reproduce the solvation forces of more
      detailed explicit solvent simulations. In this article, we compare PBE and SASA
      solvation forces with explicit solvent forces for several snapshots from eight
      trajectories of static conformations of intestinal fatty acid binding protein.
      The results from this comparison show that current implementations of the PBE are
      capable of generating polar solvation forces that correlate well with explicit
      solvent forces but systematically overestimate the magnitude of the interaction.
      However, SASA-based nonpolar forces are found to have no significant correlation
      with nonpolar explicit solvent forces. Nevertheless, due to the small magnitude
      of the nonpolar forces in the current system, a good correlation is still
      obtained for total solvation forces. The good correlation of implicit solvent
      forces with more detailed explicit solvent models is encouraging and implies that
      the systematic errors identified in these models could be corrected by
      appropriate parameterization of the force fields.

PMID- 15264257
TI  - Optimization and dynamics of protein-protein complexes using B-splines.
AB  - A moving-grid approach for optimization and dynamics of protein-protein complexes
      is introduced, which utilizes cubic B-spline interpolation for rapid energy and
      force evaluation. The method allows for the efficient use of full electrostatic
      potentials joined smoothly to multipoles at long distance so that multiprotein
      simulation is possible. Using a recently published benchmark of 58 protein
      complexes, we examine the performance and quality of the grid approximation,
      refining cocrystallized complexes to within 0.68 A RMSD of interface atoms, close
      to the optimum 0.63 A produced by the underlying MMFF94 force field. We quantify
      the theoretical statistical advantage of using minimization in a stochastic
      search in the case of two rigid bodies, and contrast it with the underlying cost
      of conjugate gradient minimization using B-splines. The volumes of conjugate
      gradient minimization basins of attraction in cocrystallized systems are
      generally orders of magnitude larger than well volumes based on energy thresholds
      needed to discriminate native from nonnative states; nonetheless, computational
      cost is significant. Molecular dynamics using B-splines is doubly efficient due
      to the combined advantages of rapid force evaluation and large simulation step
      sizes. Large basins localized around the native state and other possible binding
      sites are identifiable during simulations of protein-protein motion. In addition
      to providing increased modeling detail, B-splines offer new algorithmic
      possibilities that should be valuable in refining docking candidates and studying
      global complex behavior.

PMID- 15264258
TI  - Energetic and topological analysis of the reaction of Mo and Mo2 with NH3, C2H2,
      and C2H4 molecules.
AB  - The Density functional theory has been applied to characterize the structural
      features of Mo(1,2)-NH(3),-C(2)H(4), and -C(2)H(2) compounds. Coordination modes,
      geometrical structures, and binding energies have been calculated for several
      spin multiplets. It has been shown that in contrast to the conserved spin cases
      (Mo(1,2)-NH(3)), the interaction between Mo (or Mo(2)) and C(2)H(4) (or C(2)H(2))
      are the low-spin (Mo-C(2)H(4) and -C(2)H(2)) and high-spin (Mo(2)-C(2)H(4) and 
      C(2)H(2)) complexes. In the ground state of Mo(1,2)-C(2)H(4) and -C(2)H(2), the
      metal-center always reacts with the C-C center. The spontaneous formation of the
      global minima is found to be possible due to the crossing between the potential
      energy surfaces (ground and excited states with respect to the metallic center).
      The bonding characterization has been performed using the topological analysis of
      the Electron Localization Function. It has been shown that the most stable
      electronic structure for a pi-acceptor ligand correlates with a maximum charge
      transfer from the metal center to the C-C bond of the unsaturated hydrocarbons,
      resulting in the formation of two new basins located on the carbon atoms (away
      from hydrogen atoms) and the reduction of the number of attractors of the C-C
      basin. The interaction between Mo(1,2) and C(2)H(4) (or C(2)H(2)) should be
      considered as a chemical reaction, which causes the multiplicity change.
      Contrarily, there is no charge transfer between Mo(1,2) and NH(3), and the
      partners are bound by an electrostatic interaction.

PMID- 15264260
TI  - Counting cats in Zanzibar.

PMID- 15264259
TI  - A biomolecular force field based on the free enthalpy of hydration and solvation:
      the GROMOS force-field parameter sets 53A5 and 53A6.
AB  - Successive parameterizations of the GROMOS force field have been used
      successfully to simulate biomolecular systems over a long period of time. The
      continuing expansion of computational power with time makes it possible to
      compute ever more properties for an increasing variety of molecular systems with
      greater precision. This has led to recurrent parameterizations of the GROMOS
      force field all aimed at achieving better agreement with experimental data. Here
      we report the results of the latest, extensive reparameterization of the GROMOS
      force field. In contrast to the parameterization of other biomolecular force
      fields, this parameterization of the GROMOS force field is based primarily on
      reproducing the free enthalpies of hydration and apolar solvation for a range of
      compounds. This approach was chosen because the relative free enthalpy of
      solvation between polar and apolar environments is a key property in many
      biomolecular processes of interest, such as protein folding, biomolecular
      association, membrane formation, and transport over membranes. The newest
      parameter sets, 53A5 and 53A6, were optimized by first fitting to reproduce the
      thermodynamic properties of pure liquids of a range of small polar molecules and
      the solvation free enthalpies of amino acid analogs in cyclohexane (53A5). The
      partial charges were then adjusted to reproduce the hydration free enthalpies in
      water (53A6). Both parameter sets are fully documented, and the differences
      between these and previous parameter sets are discussed.

PMID- 15264261
TI  - Patterns and predictors of sleep pattern disturbance after cardiac surgery.
AB  - The purposes of this study were to examine changes in sleep patterns after
      cardiac surgery and the contributions of preoperative sleep to postoperative
      sleep. Seventy-two cardiac surgery patients wore wrist actigraphs for 3 days
      during the preoperative period (T1) and the 1st (T2), 4th (T3), and 8th (T4)
      postoperative weeks. They completed the Pittsburgh Sleep Quality Index at T1, T3,
      and T4. Sleep was most disturbed during the 1st postoperative week and improved
      at T3 and T4. Overall, sleep pattern disturbance was higher at T3 and T4 than at
      T1. Age, gender, preoperative New York Heart Association Functional Class, and
      preoperative sleep variables explained 20%-50% of the variance in sleep at T2,
      T3, and T4. Sleep disturbance is present preoperatively and continues during the
      postoperative period.

PMID- 15264262
TI  - Variations in sleep hygiene practices of women with and without insomnia.
AB  - Sleep hygiene education is a basic component of behavioral treatment for chronic
      insomnia, yet the actual sleep hygiene practices of people with insomnia have not
      been well documented. In this descriptive secondary analysis, midlife women ages
      41-55 years with either chronic insomnia (n = 92) or good sleep (n = 29) kept
      diaries of sleep perceptions and sleep hygiene practices during 6 nights of
      somnographic monitoring at home. In both groups few reported smoking cigarettes
      (<10%), most drank caffeine (>80%), and many averaged 30 min of exercise per day
      ( approximately 50%). Very few in either group (<10%) had regular (<30 min
      variation) bedtimes or getting-up times. Compared to women with good sleep, those
      with insomnia reported drinking less caffeine per day, being more abstinent from
      alcohol, and having smaller variations in day-to-day alcohol intake and bedtimes.
      Although some women with insomnia limit or refrain from caffeine and alcohol
      intake, many have not optimized behaviors believed to help prevent or modulate
      insomnia.

PMID- 15264263
TI  - Adolescents' coping with surgery for scoliosis: effects on recovery outcomes over
      time.
AB  - Surgery for adolescent idiopathic scoliosis is painful and stressful and has a
      long and demanding recovery. The purpose of this study was to examine pre- and
      postoperative avoidant/vigilant coping and long-term activity outcomes through 9
      months postsurgery for adolescents (11-18 years, N = 113) undergoing scoliosis
      surgery. Generally, more vigilant copers (preoperatively and 1 month
      postoperatively) participated in more activities (usual, new, and social) and had
      higher academic performance during recovery. Several moderation effects indicated
      these relationships were stronger for older adolescents and those more internal
      in locus of control. Adolescents were more vigilant in the hospital, became more
      avoidant 1 month after surgery, and remained at these levels 6 months
      postsurgery. Understanding coping processes and individual factors is necessary
      to develop interventions to help adolescents cope successfully with recovery
      demands.

PMID- 15264264
TI  - Predictors of patient satisfaction with inpatient hospital nursing care.
AB  - The purpose of this predictive nonexperimental study was to investigate the
      influence of registered nurse (RN) job satisfaction, context of care, structure
      of care, patient-perceived nurse caring, and patient characteristics on patient
      satisfaction with inpatient hospital nursing care in an academic medical center
      in north-central West Virginia. Convenience samples of patients (N = 362) and RNs
      (N = 90) were recruited from two medical units, two surgical units, and three
      intensive care step-down units. Causal modeling identified patient-perceived
      nurse caring as the major predictor of patient satisfaction, with nurse/physician
      (RN/MD) collaboration as the only other direct predictor. Age had an indirect
      influence on patient satisfaction. Strategies to achieve and maintain patient
      satisfaction should address the enhancement of patient-perceived nurse caring and
      RN/MD collaboration.

PMID- 15264265
TI  - Effectiveness of a videotape for sexual counseling after myocardial infarction.
AB  - A two-group randomized clinical trial was used to test the hypothesis that
      patients with myocardial infarction (MI) who receive both written instructions
      and a videotape to view at home will have greater knowledge, better quality of
      life, less anxiety, greater sexual satisfaction, and will resume sexual activity
      more quickly than will those who receive written instructions alone. The
      participants, 115 patients diagnosed with an MI, were pretested in the hospital
      and followed at home at 1, 3, and 5 months. The intervention was an educational
      videotape on return to sexual activity. Significant improvements in knowledge
      were found for the experimental group at 1 month. The videotape intervention
      provides an alternative method for education to facilitate recovery post-MI.

PMID- 15264266
TI  - Cigarette smoking: Evidence to guide measurement.
AB  - Smoking cessation programs measure outcomes in terms of abstinence from or
      reduction in smoking. These outcomes can be measured through self-report by the
      smoker, through measurement with a biological marker of smoking, or through a
      combination of both. Consideration of the relative advantages of self-report and
      biomarker approaches is important in the selection of measurement strategies to
      evaluate outcomes in smoking cessation interventions. In this article both ways
      of measuring smoking behavior, self-report and biomarkers of carbon monoxide,
      cotinine, nicotine, thiocyanate, and alkaloids of nicotine, are explored.
      Measurement approaches are discussed in light of research evidence and their
      physiologic bases.

PMID- 15264267
TI  - Inherited cancer predisposition.

PMID- 15264268
TI  - Inherited predisposition to cancer: a historical overview.
AB  - The hereditary predisposition to cancer dates historically to interest piqued by
      physicians as well as family members wherein striking phenotypic features were
      shown to cluster in families, inclusive of the rather grotesque cutaneous
      findings in von Recklinghausen's neurofibromatosis, which date back to the
      sixteenth century. The search for the role of primary genetic factors was
      heralded by studies at the infrahuman level, particularly on laboratory mouse
      strains with strong susceptibility to carcinogen-induced cancer, and conversely,
      with resistance to the same carcinogens. These studies, developed in the 19th and
      20th centuries, continue today. This article traces the historical aspects of
      hereditary cancer dealing with identification and ultimate molecular genetic
      confirmation of commonly occurring cancers, particularly of the colon in the case
      of familial adenomatous polyposis and its attenuated form, both due to the APC
      germline mutation; the Lynch syndrome due to mutations in mismatch repair genes,
      the most common of which were found to be MSH2, MLH1, and MSH6 germline
      mutations; the hereditary breast-ovarian cancer syndrome with BRCA1 and BRCA2
      germline mutations; the Li-Fraumeni (SBLA) syndrome due to the p53 mutation; and
      the familial atypical multiple mole melanoma in association with pancreatic
      cancer due to the CDKN2A (p16) germline mutation. These and other hereditary
      cancer syndromes have been discussed in some detail relevant to their
      characterization, which, for many conditions, took place in the late 18th century
      and, in the more modern molecular genetic era, during the past two decades.
      Emphasis has been placed upon the manner in which improved cancer control will
      emanate from these discoveries.

PMID- 15264269
TI  - Retinoblastoma: revisiting the model prototype of inherited cancer.
AB  - Hereditary retinoblastoma is an autosomal dominant disorder caused by mutations
      in the RB1 gene. Analysis of this rare condition has helped to elucidate the
      mechanisms underlying hereditary cancer predisposition in general. As
      identification of RB1 gene mutations has become a part of clinical management of
      patients with retinoblastoma, there is now a wealth of data. In this article, we
      summarize the current knowledge on the relations between the genotype and
      phenotypic expression. Moreover, detailed analysis of genotype-phenotype
      relations shows that hereditary retinoblastoma has features of a complex trait.

PMID- 15264270
TI  - Familial Wilms tumor.
AB  - Wilms tumor (WT), an embryonic tumor arising from undifferentiated renal
      mesenchyme, has been a productive model for understanding the role of genes in
      both tumorigenesis and normal organogenesis. Approximately 2% of WT patients have
      a family history of WT, and even sporadic WT is thought to have a strong genetic
      component to its etiology. Familial WT cases generally have an earlier age of
      onset and an increased frequency of bilateral disease, although there is
      variability among WT families, with some families displaying later than average
      ages at diagnosis. One WT gene, WT1 at 11p13, has been cloned, but only a
      minority of tumors carry detectable mutations at that locus, and it can be
      excluded as the predisposition gene in most WT families. Two familial WT genes
      have been localized, FWT1 at 17q12-q21 and FWT2 at 19q13.4; lack of linkage in
      some WT families to either of these loci implies the existence of at least one
      additional familial WT gene. Originally modeled as the inheritance of a mutation
      in a tumor suppressor gene, molecular analysis of familial tumors not linked to
      11p13 have provided data suggesting that this model may be overly simplistic
      and/or not applicable to all WT families. Identification of the FWT1 and FWT2
      genes will help clarify this and will also likely aid in our understanding in
      general of the roles of the various WT genes and their genetic interactions in
      the development of WT.

PMID- 15264271
TI  - Simple and complex genetics of colorectal cancer susceptibility.
AB  - There are several hereditary conditions associated with an increased risk of
      colorectal cancer (CRC). These include well-characterized autosomal dominant
      syndromes, such as familial adenomatous polyposis (FAP) and hereditary
      nonpolyposis colorectal cancer (HNPCC). A novel autosomal recessive form of FAP,
      caused by mutations in the base excision repair gene MYH, has recently been
      recognized. This discovery has provided further evidence for the importance of
      DNA repair mechanisms in CRC development, already documented by the involvement
      of the mismatch repair in HNPCC. Additional CRC-predisposing conditions, such as
      hyperplastic polyposis and hereditary mixed polyposis syndrome, are being
      outlined. Heterogeneity of genetic mechanisms has important consequences for
      counseling and surveillance in hereditary CRC. Nevertheless, classical mendelian
      conditions represent only a minor share of the total CRC population burden.
      Alleles of the same genes that are involved in hereditary syndromes might also
      act as low penetrance variants, as shown for APC 1307K in the Ashkenazi. However,
      the level of complexity of multifactorial CRC is such that current tools appear
      inadequate to pinpoint all the involved components. A combination of different
      strategies, including careful clinical observation, analysis of homogeneous
      patient populations, and critical evaluation of data derived from experimental
      models, along with methodological improvements in nucleic acid analysis, will
      probably be necessary to unravel the basis of nonmendelian CRC. Once this is
      achieved, it will be possible to realize the ultimate goal of targeted CRC
      prevention, with the adoption of measures tailored according to individual risk
      levels. .

PMID- 15264272
TI  - Genetic conditions associated with intestinal juvenile polyps.
AB  - Juvenile polyps are hamartomatous polyps found primarily in infants and children,
      and in association with juvenile polyposis (JP; OMIM #174900), Cowden syndrome
      (CS; OMIM #158350), and Bannayan-Riley-Ruvalcaba syndrome (BRRS; OMIM# 153480).
      Although solitary juvenile polyps are benign lesions, when present in JP patients
      they may lead to gastrointestinal cancers. Germline mutations in MADH4 and BMPR1A
      predispose to JP, and both genes are involved in TGF-beta superfamily signaling
      pathways. In CS and BRRS, juvenile polyps are a less consistent feature, and CS
      patients are at risk for breast and thyroid cancers. Mutations of the tumor
      suppressor gene PTEN have been found in the germline of both CS and BRRS
      patients. Despite different underlying genetic mechanisms, these and other
      syndromes share the same phenotypic feature of juvenile polyps.

PMID- 15264273
TI  - Breast cancer genetics: unsolved questions and open perspectives in an expanding
      clinical practice.
AB  - Breast cancer is the most common cause of cancer death in the United Kingdom,
      with a lifetime risk of one in nine in women. Only 5-10% of all cancers is
      thought to be due to strongly penetrant inherited predisposing genes, such as
      BRCA1 and BRCA2. However, other less penetrant genes, including some autosomal
      recessive genes, are likely to be of etiological importance in other families.
      This review addresses the current knowledge of breast cancer susceptibility genes
      and explores the possibilities for future developments. Features of tumor
      pathology, prognosis, and the scope for targeted treatments in mutation carriers
      are discussed, and the management of known carriers and those at increased risk
      for developing breast cancer are evaluated. Genetic testing for cancer
      susceptibility may become widely available in the future, and has important
      ethical and management implications.

PMID- 15264274
TI  - Unravelling the genetics of prostate cancer.
AB  - This review describes what is currently known about the genetics of prostate
      cancer. Traditionally, the genetics of a suspected inherited cancer
      predisposition have generally been thought of in terms of a single, high-risk
      gene with a dominant mode of inheritance. Such a gene might be observed in
      families, as has been documented in familial breast cancer (BRCA1/2), familial
      colorectal cancer (HNPCC), retinoblastoma (RB1), and Wilms tumor (WT1). This
      review investigates the evidence for the existence, first of familial prostate
      cancer, and second, for the presence of such a high-risk gene in those families
      by epidemiological and experimental approaches. Another current area of interest
      in prostate cancer is the investigation of the contribution of common lower
      penetrance genes to the disease. This alternative approach has become popular, as
      it raises the issue of frequently seen genetic variations such as single
      nucleotide polymorphisms (SNPs) having relevance to the risk of developing the
      disease. Finally, this article will explore the way forward, with emphasis on
      worldwide collaboration from teams attempting to find the genes responsible for
      the disease and investment in new technologies that will aid in their discovery.

PMID- 15264275
TI  - Genetic insights into familial tumors of the nervous system.
AB  - Nervous system tumors represent unique neoplasms that arise within the central
      and peripheral nervous system. While the vast majority of nervous system neoplasm
      occur sporadically, most of the adult and pediatric forms have a hereditary
      equivalent. In a little over a decade, we have seen a tremendous increase in
      knowledge of the primary genetic basis of many of the familial cancer syndromes
      that involve the nervous system, syndromes that are mostly inherited as autosomal
      dominant traits. In this review, we discuss the most recent findings on the
      genetic basis of hereditary nervous system tumors. The identification of genes
      associated with familial cancer syndromes has in some families enabled a
      "molecular diagnosis" that complements clinical assessment and allows directed
      cancer surveillance for those individuals determined to be at-risk for disease.

PMID- 15264276
TI  - Genomic imprinting and environment in hereditary paraganglioma.
AB  - Hereditary paraganglioma (PGL) is characterized by the development of slow
      growing and vascularized tumors in the paraganglionic system. PGL is caused by
      germ line heterozygous inactivating mutations in the SDHB (PGL4), SDHC (PGL3), or
      SDHD (PGL1) genes, which encode three of the four subunits of mitochondrial
      complex II (succinate dehydrogenase; SDH). Common tumor sites include the carotid
      body in the neck and paraganglia in the abdomen. The risk of tumor development
      associated with SDHD mutations is determined by the sex of the transmitting
      parent, because only a paternal transmission leads to tumorigenesis in the
      progeny. This transmission pattern suggests operation of genomic imprinting on
      the SDHD gene. There is also evidence that the risk of tumor development
      increases at higher altitudes among SDHD mutation carriers. Accordingly, the
      increased prevalence of SDHD mutations in the Netherlands, attributable to
      multiple founder mutations, has been explained in part by the low altitudes in
      this country, which presumably reduce gene penetrance and relax the natural
      selection. Thus, PGL caused by SDHD mutations represents an unusual example of an
      inherited monogenic tumor syndrome because the risk of tumorigenesis shows an
      absolute dependence on the sex of the transmitting parent and may be modified by
      a ubiquitous environmental factor.

PMID- 15264277
TI  - Loss of DNA mismatch repair function and cancer predisposition in the mouse:
      animal models for human hereditary nonpolyposis colorectal cancer.
AB  - Germline mutations in DNA mismatch repair genes underlie one of the most common
      hereditary cancer predisposition syndromes known in humans, hereditary
      nonpolyposis colorectal cancer (HNPCC). Defects of the DNA mismatch repair system
      are also prevalent in sporadic colorectal cancers. The generation of mice with
      targeted inactivating mutations in the mismatch repair genes has facilitated the
      in vivo study of how these genes function and how their individual loss
      contributes to tumorigenesis. Although there are notable limitations when using
      murine models to study the molecular basis of human cancer, there is remarkable
      similarity between the two species with respect to the contribution of individual
      members of the mismatch repair system to cancer susceptibility, and mouse mutants
      have greatly enhanced our understanding of the normal role of these genes in
      mutation avoidance and suppression of tumorigenesis.

PMID- 15264278
TI  - Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in
      two patients with Antley-Bixler syndrome.
AB  - Antley-Bixler syndrome (ABS) is characterized by skeletal defects including
      craniosynostosis and radiohumeral synostosis. Although mutations in the FGFR2
      gene have been found in some patients called ABS, genetic heterogeneity of this
      syndrome has been proposed. We have previously reported three ABS patients with
      unique abnormalities in steroidogenesis (apparent decreased activity of 17alpha
      hydroxylase, 17,20-lyase, and 21-hydroxylase). Decreased activity of lanosterol
      14alpha-demethylase has also been described in an ABS patient. Since all these
      enzymes require cytochrome P450 oxidoreductase (encoded by POR) as an electron
      donor, we studied POR in two unrelated ABS patients with abnormal
      steroidogenesis. Direct sequencing of POR revealed that both patients had
      compound heterozygous mutations (1329insC and R454H in a male patient, 1698insC
      and R454H in a female patient). The two insertional mutations were assumed to
      generate truncated and unstable mRNAs. The R454H mutation was assumed to be
      deleterious because the R454 resides in the FAD-binding domain and is highly
      conserved among diverse species. Our results demonstrate that mutations in POR
      cause the ABS phenotype with autosomal recessive inheritance and with
      characteristic abnormalities in steroidogenesis.

PMID- 15264279
TI  - Subtelomeric deletions of chromosome 9q: a novel microdeletion syndrome.
AB  - Fluorescent in situ hybridization (FISH) screening of subtelomeric rearrangements
      has resulted in the identification of previously unrecognized chromosomal causes
      of mental retardation with and without dysmorphic features. This article reports
      the phenotypic and molecular breakpoint characterization in a cohort of 12
      patients with subtelomeric deletions of chromosome 9q34. The phenotypic findings
      are consistent amongst these individuals and consist of mental retardation,
      distinct facial features and congenital heart defects (primarily conotruncal
      defects). Detailed breakpoint mapping by FISH, microsatellite and single
      nucleotide polymorphism (SNP) genotyping analysis has narrowed the commonly
      deleted region to an approximately 1.2 Mb interval containing 14 known
      transcripts. The majority of the proximal deletion breakpoints fall within a 400
      kb interval between SNP markers C12020842 proximally and C80658 distally
      suggesting a common breakpoint in this interval.

PMID- 15264280
TI  - Clinical presentation of 13 patients with subtelomeric rearrangements and a
      review of the literature.
AB  - To re-examine the potential clinical indications for subtelomeric FISH testing
      and to provide additional cases to the growing literature on subtelomeric
      abnormalities and their genotype-phenotype correlations, we present a single
      center case series of 13 patients with chromosomal abnormalities detected by
      subtelomeric FISH testing over a 21 month period. The most common abnormality
      involved chromosome 1p (23%). Partial monosomy was present in 69% of the
      patients, complex rearrangements in 23%, and partial trisomy in 8%. The mean time
      from first normal karyotype to positive subtelomeric FISH result was 3.8 years (n
      = 11, median 3.5 years, range: 6 months-10 years). One patient had an abnormal
      high resolution karyotype recognized retrospectively, and two other patients had
      abnormal karyotypes that were fully deciphered only after subtelomeric FISH
      analysis. Eighty five percent of cases occurred de novo. The subtelomeric FISH
      results were useful for adjusting the recurrence risks and helping to focus
      medical screening and monitoring. The results impacted family planning and
      satisfied families in search of a diagnosis. Our findings support the use of
      subtelomeric FISH analysis as a second tier test in patients suspected of having
      a chromosomal abnormality with a normal karyotype. Potential benefits of
      subtelomeric FISH testing include faster time to diagnosis, better informed
      patient prognosis, and more accurate genetic counseling.

PMID- 15264281
TI  - Subtelomere FISH in 50 children with mental retardation and minor anomalies,
      identified by a checklist, detects 10 rearrangements including a de novo balanced
      translocation of chromosomes 17p13.3 and 20q13.33.
AB  - Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed
      by subtelomere fluorescence in situ hybridization (FISH), are a significant cause
      of idiopathic mental retardation (MR). Some 20 subtelomere studies, including
      more than 2,500 subjects, have been reported. The studies are not directly
      comparable because different techniques and patient ascertainment criteria were
      used, but an analysis of 14 studies showed that aberrations were detected in 97
      out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60
      6.84%). We performed a subtelomere FISH study of 50 unrelated children
      ascertained by a checklist that evaluates MR or developmental delay, dysmorphism,
      growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements
      (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced
      familial translocations or inversions, two unbalanced de novo translocations, and
      two de novo deletions. Patient 5 showed multiple anomalies (large head, vision
      defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect,
      mild transient homocysteinemia) and a de novo balanced translocation of
      chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced
      rearrangement associated with a disease phenotype is a novel one. FISH mapping
      using panels of overlapping BAC clones identified a number of candidate genes at
      or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and
      three genes of unknown function at 20q13.33. Only the homocysteinemia could be
      speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three
      within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified
      degree of MR tested positive, suggesting that the checklist approach could be
      especially useful within this group of patients.

PMID- 15264282
TI  - Familial acromelic frontonasal dysostosis: autosomal dominant inheritance with
      reduced penetrance.
AB  - Acromelic frontonasal dysostosis (AFND) represents a subgroup of patients with
      frontonasal malformation with limb abnormalities including preaxial polydactyly
      and tibial hypoplasia. Previous case reports have suggested autosomal recessive
      inheritance, given parental consanguinity. However, no affected siblings have
      been described. Longitudinal clinical history is limited as many do not survive
      the first years of life. The molecular basis of AFND is not known. Previous
      investigators have proposed that AFND may result from a perturbation in the Sonic
      Hedgehog pathway. We present clinical and radiographic findings in two unrelated
      boys, ages 8 and 9 years, with AFND, one of whom has a family history suggesting
      dominant inheritance. A focused study of genetic marker data and candidate gene
      mutation analysis in this family is presented.

PMID- 15264284
TI  - Behavioral pattern profile: a tool for the description of behavior to be used in
      the genetics clinic.
AB  - Careful descriptions of dysmorphic features have led to the delineation of
      hundreds of specific syndromes and patterns of congenital anomalies. The defining
      of unusual behavior had largely been neglected by clinical geneticists until the
      study of the natural history of microdeletions revealed that each has unique and
      characteristic behavior(s). In this study, a simple tool to describe behavior is
      presented that is to be used in the genetics clinic as part of routine
      evaluation. The form is meant to simplify recording and does not require the
      formal training needed for psychological assessments. It is hoped that routine
      recording of behavior among individuals seen in the genetics clinic will lead to
      better recognition of unusual behavior among individuals with known conditions,
      as well as the recognition of conditions characterized only by unusual behavior.
      Better description of behavioral patterns should lead to the ascertainment of
      homogeneous groups of affected individuals with abnormalities in the functional
      pathways that generate patterns of reaction. The genetic and biochemical basis
      for these patterns of reaction (abnormal behavior) should then be available for
      both natural history and molecular studies. The tool consists of 12 categories of
      behavioral features that can be assessed by the medical geneticist. The list was
      built to allow the observation of as many behavioral aspects as possible, but to
      keep it to a practical size and to use those features that are simple to describe
      and quantitate. We expect that its use will produce a rich source of behavioral
      profiles and will eventually contribute to the better understanding of unusual
      behavior.

PMID- 15264283
TI  - Impact of excluding cases with known chromosomal abnormalities on the prevalence
      of structural birth defects, Hawaii, 1986-1999.
AB  - Chromosomal abnormalities are more common in the presence of structural birth
      defects. However, much of the literature have only provided chromosomal
      abnormality rates for one or a few structural birth defects at a time. This study
      calculated the chromosomal abnormality rates for a number of structural birth
      defects using data from the Hawaii Birth Defects Program (HBDP) for deliveries
      during 1986-1999 and evaluated the impact of exclusion of cases with chromosomal
      abnormalities when calculating birth prevalence. The chromosomal abnormality
      rates were highest for endocardial cushion defect (40%) and omphalocele (27%),
      while no chromosomal abnormalities were reported for pyloric stenosis, persistent
      cloaca, and deficiency of lower limbs. The majority of chromosomal abnormality
      rates fell within a certain range, with 32 (63%) of the birth defect categories
      having chromosomal abnormality rates of 5-15%. The chromosomal abnormality rates
      also tended to be higher for multiple than for isolated cases. For three of the
      structural birth defects (ventricular septal defect, atrial septal defect,
      endocardial cushion defect), the birth prevalence of the defect, when cases with
      a chromosomal abnormality were excluded, was significantly lower than the birth
      prevalence that included those cases. Chromosomal abnormality rates varied by
      type of structural birth defect and presence of other major structural birth
      defects. For at least several structural birth defects, exclusion of cases with
      chromosomal abnormalities significantly underestimated the birth prevalence. This
      underestimation may be important, depending on the purpose of the analysis.

PMID- 15264285
TI  - Adaptive skills, cognitive, and behavioral characteristics of Costello syndrome.
AB  - Costello syndrome is a rare congenital disorder whose diagnosis is based on
      clinical findings. The underlying genetic cause has not been identified. Common
      characteristics include failure to thrive, feeding problems, short stature,
      coarsening of facial features, developmental delay, mental retardation, skeletal
      problems, cardiac complications, and increased risk for solid tumors. Given its
      rarity, existing literature is limited regarding its natural course.
      Developmental milestones and intellectual functioning have never been
      systematically studied in this population, therefore this study focused on
      defining developmental and intellectual attributes. Data was obtained through
      solicited participation at the 3rd International Costello Syndrome Meeting. A
      total of 18 children (age 3-20 years) were administered the Leiter-R brief-IQ and
      the Peabody picture vocabulary test (PPVT)-III to assess nonverbal cognitive
      functioning and receptive vocabulary. Parents/guardians completed the child
      behavior checklist (CBCL) and participated in an interview process to complete
      the survey form of the Vineland adaptive behavior scales to assess
      emotional/behavioral issues and adaptive behavior. Results indicated that
      nonverbal cognitive functioning ranged from 1.5 to 4.3 SD below the age mean.
      Receptive vocabulary skills ranged from average functioning to 4 SD below the age
      mean. Adaptive behavior composites were all in the low range (2.0 to >5.0 SD
      below age mean), however there was significant variability in the range of domain
      scores. CBCL results ranged from normal to clinically significant across various
      clinical parameters. These data support a generalized descriptive pattern of
      developmental delay and mental retardation, with noted variability in receptive
      language, level of adaptive behavior functioning, and emotional/behavioral
      aspects. Skills and behavior are compared to existing literature of children with
      various syndromes.

PMID- 15264287
TI  - Mesomelic dysplasia, Kantaputra type: clinical report, prenatal diagnosis, no
      evidence for SHOX deletion/mutation.
AB  - A grandmother, her three children, and three grandchildren had skeletal
      abnormalities consisting of a short stature, bilateral symmetrical very short,
      broad and bowed radii, very short and broad ulna, mildly short lower legs, short
      proximal end of fibula, abnormal ankles, abnormal calcaneus and talus and pes
      equinus. They had normal craniofacial features, normal intelligence and normal
      chromosomes. We concluded that this skeletal dysplasia resembles the autosomal
      dominant mesomelic dysplasia, Kantaputra type. Prenatal diagnosis by ultrasound
      examination early in the pregnancy was possible. We found no evidence for a SHOX
      gene deletion or point mutation. As far as we know this is the third reported
      family with this skeletal dysplasia.

PMID- 15264286
TI  - A novel MSX1 mutation in hypodontia.
AB  - MSX1 mutations have been reported in four unrelated families with autosomal
      dominant tooth agenesis. In one family, some individuals also had cleft lip
      and/or palate. We have identified a novel MSX1 mutation (559 C --> T, resulting
      in Gln187Stop) in three individuals of one family.

PMID- 15264288
TI  - Molecular characterization of a cryptic 2q37 deletion in a patient with Albright
      hereditary osteodystrophy-like phenotype.
AB  - The Albright hereditary osteodystrophy-like (AHO-like) syndrome was recently
      defined as a rare dysmorphic syndrome including brachymetaphalangism and mental
      retardation. This phenotype occurs in Albright hereditary osteodystrophy (AHO)
      but unlike it, the level of the Gs alpha protein activity is not reduced. To date
      59 patients with these clinical and biochemical features have been reported, and
      for the majority of them (57/59) a cytogenetically visible 2q37 deletion has been
      observed. We report a new case of typical AHO-like syndrome with normal
      karyotype. Using the polymorphic marker D2S125 we found a loss of heterozygosity
      suggestive of a de novo 2q37 deletion of maternal origin. This hypothesis was
      confirmed by FISH analysis with a subtelomeric 2q probe containing the D2S90
      marker. Genotypic analysis allowed us to map the proximal breakpoint of the
      subtelomeric deletion within an interval delimited by D2S2338 (present) and
      D2S2253 (deleted). This 2q subtelomeric deletion as small as 4 Mb is to date the
      smallest one observed in association with a typical AHO-like phenotype, and
      allows us to move the centromeric boundary of the AHO-like critical region by 750
      kb towards the 2q telomere.

PMID- 15264289
TI  - New autosomal recessive syndrome with short stature and facio-auriculo-thoracic
      malformations.
AB  - Two sibs, a boy and a girl, from a Lebanese consanguineous family presented with
      short stature, microcephaly, ptosis, small, dysplastic, low set ears, short neck,
      and pectum excavatum and carinatum. In addition, the boy had a high arched
      palate, a cardiac malformation, and at the X-rays an absence of fusion of the
      posterior hemi-arches of C7 and a fusion between L5 and S1 with a sagittal-cleft
      vertebral body of L5, while his sister had a cleft lip/palate and at the X-rays
      an abnormal odontoid peg and a malformation of the articular facets between C1
      and C2, and bilateral cervical ribs. Other laboratory and radiological
      investigations were normal. Sequencing of PTPN11 exons 2, 3, 4, 7, 8, 12, and 13
      did not reveal any variations. Two other sibs presented almost the same
      dysmorphic features; one girl died at age 6(1/4) years after an acute episode of
      renal insufficiency, and one boy died at 40 days of age. Differential diagnosis
      is discussed and the possibility of the report of a new autosomal recessive
      syndrome with variable expressivity is raised.

PMID- 15264290
TI  - Primary trabeculodysgenesis in association with neonatal Marfan syndrome.
AB  - We present the clinical and ophthalmological findings in two infants with
      neonatal Marfan syndrome (nMFS) and primary trabeculodysgenesis (PT). Fibrillin 1
      (FBN1) mutations were confirmed in both cases. Numerous eye anomalies have been
      recognized in infants with nMFS, but PT has not been reported previously. Our
      report expands the phenotype of nMFS, and highlights the importance of early and
      careful ophthalmological assessment of these infants.

PMID- 15264291
TI  - Inverted duplication of 15q with terminal deletion in a multiple malformed
      newborn with intrauterine growth failure and lethal phenotype.
AB  - We describe the cytogenetic and molecular characterization of an inverted
      duplication of chromosome 15q with evidence of a terminal deletion of the same
      rearranged chromosome. The proband was a multiple congenital malformed female
      with a prenatal diagnosis of trisomy 15q and an extremely severe clinical course.
      The phenotype of the patient was characterized by marked intrauterine growth
      retardation, congenital heart defect, "horseshoe" kidney, hand contractures, and
      clubfeet. The exitus came at 20 days because of progressive cardio-respiratory
      impairment. Overall, the clinical phenotype appeared more severe than usual
      trisomy 15q syndrome. Postnatal cytogenetic and molecular studies unraveled a "de
      novo" inverted duplication of 15q (q21.3-->q26.3), associated with the deletion
      of the 15q telomere and part of the band 15q26.3. A single copy region spanning
      approximately 600 kb between the duplicated segments was present. Correlation
      between the clinical findings of the patient and the phenotype of trisomy 15q
      reported in literature is also provided.

PMID- 15264292
TI  - Endangered species.

PMID- 15264293
TI  - Mutations in IRF6 do not cause Bartsocas-Papas syndrome in a family with two
      affected sibs.

PMID- 15264294
TI  - Dent disease-like phenotype and the chloride channel ClC-4 (CLCN4) gene.

PMID- 15264295
TI  - Discordance between phenotypic appearance and genotypic findings in a familial
      case of classical Ehlers-Danlos syndrome.

PMID- 15264296
TI  - A novel NOG mutation Pro37Arg in a family with tarsal and carpal synostoses.

PMID- 15264297
TI  - Comparison of in vitro with in vivo characteristics of wear particles from metal
      metal hip implants.
AB  - The purpose of the present study was to compare wear particles isolated from
      metal-metal (MM) hip implants worn in an orbital bearing simulator with particles
      from similar MM total hip replacement (THR) implants worn in vivo. Comparison of
      these particles is important because it will help to assess the overall
      suitability of this type of hip simulator for reproducing in vivo wear and for
      producing physiological wear particles suitable for biological studies of in
      vitro cellular response. Commercial grade components made of ASTM F75 (cast)
      alloy were evaluated. Simulator tests were performed in 95% bovine calf serum
      with a 28-mm-diameter implant. Wear particles were collected from 0 to 0.25
      million cycles (run-in wear period) and 1.75 to 2 million cycles (steady-state
      wear period). Tissues from seven patients with MM implants (surface replacement
      or stem type) were harvested at revision surgeries (after 1-43 months). Metal
      wear particles were isolated from serum lubricant or tissues using an enzymatic
      protocol that was previously optimized to minimize particle changes due to
      reagents. After isolation, particles were centrifuged, embedded in epoxy resin,
      and characterized by transmission electron microscopy (TEM) and energy dispersive
      X-ray analysis (EDXA). Results of EDXA on particles from the hip simulator
      primarily indicated a predominance of particles containing Cr and O but no Co
      (most likely chromium oxide particles), and fewer CoCrMo particles presenting
      varying ratios of Co and Cr. Image analysis of TEM micrographs demonstrated that
      the majority of the particles from the simulator were round to oval, but a
      substantial number of needle-shaped particles were also found, especially from 0
      to 0.25 Mc. The particles generated from 0 to 0.25 Mc had an average length of 53
      nm, whereas those generated from 1.75 to 2 Mc had an average length of 43 nm. In
      vivo, EDXA and TEM analysis of particles that were retrieved from two patients at
      23 and 43 months respectively, revealed that they were the most comparable in
      composition, average length (57 nm), and shape to particles generated in the hip
      simulator during the run-in wear period. Because a large clinical retrieval study
      in the literature suggested that a run-in wear regime might occur in vivo for
      some 6-36 months, the fidelity of the simulator of the present study was strongly
      supported. However, some uncertainties existed, including the finding that the
      particles isolated from the other five patients generated from 1 month up to 15
      months (shorter implantation times than the other two patients) were smaller and
      mostly contained only Cr and O (no Co). In the opinion of the authors, this
      particular very short term patient group was somewhat atypical. Therefore,
      despite these uncertainties, the present study was deemed to support the ability
      of the orbital bearing hip simulator to produce physiological wear particles.

PMID- 15264298
TI  - The role of implant alignment on stability and particles on periprosthetic
      osteolysis--A rabbit model of implant failure.
AB  - The study objective was to determine the tissue response to polyethylene and/or
      titanium particles and the role that these play in peri-prosthetic osteolysis in
      a rabbit model of implant failure. Twenty-two mature rabbits were used.
      Unilateral tibial arthroplasty was performed on all of them. The test animals
      received implants that were intentionally rotationally unstable with reference to
      the host tibia in order to create a model of failure. The test rabbits were
      divided into three groups. Group 1 consisted of seven rabbits in which only the
      carrier was implanted. Group 2 consisted of seven rabbits that received only
      polyethylene particles suspended in the carrier. Group 3 consisted of eight
      rabbits that received a mixture of polyethylene and titanium alloy particles
      suspended in the carrier. The rabbits were sacrificed at 6 months post surgery.
      The entire knee, together with the immediately surrounding soft tissue, was
      retrieved. The position of the implant in each rabbit was assessed with reference
      to its alignment to the tibia. The number of inflammatory, foreign-body reactive
      cells, the presence of neovascularization, edema, and necrosis in the
      periprosthetic zones were recorded and assessed in a qualitative and
      semiquantitative manner. Quantitative histomorphometry was used to determine the
      proportion of implant surface that interfaced with osseous or fibrous tissue.
      Also assessed was the thickness and maturity of the fibrous tissue and the
      endosteal remodeling activity in the peri-implant bone counting both osteoclastic
      and osteoblastic activity. The results showed that implanted particles and
      misalignment of the implants combined to produce peri-prosthetic bone resorption.
      Bone resorption was found to be proportional to the degree of misalignment. The
      animals that received combined polyethylene/titanium particles had a greater
      degree of foreign-body and inflammatory response with osteolysis than the other
      groups. The combination of bio-material particles (polyethylene and titanium
      alloy) produced a greater degree of bone resorption than the single biomaterial
      particles (polyethylene). The amount of bone resorption surrounding the implant
      was directly proportional to the degree of misalignment of the implant.

PMID- 15264299
TI  - Surface modification of titanium implant by microarc oxidation and hydrothermal
      treatment.
AB  - Surface modification of titanium implant is processed by microarc oxidation and
      hydrothermal treatment. A porous surface with a biologically active bone-like
      apatite layer was formed. The apatite layer consists of very fine crystals and
      high crystallinity and is integrated with the titanium alloy substrate with a
      graded structure without a distinct interface. Such a bioactive layer is expected
      not only to enhance the bony ingrowth into the porous structure, but also to
      improve the interlocking between implant and bone.

PMID- 15264300
TI  - Poly(vinyl alcohol) membranes for adhesion prevention.
AB  - The abnormal joining of anatomic structures after abdominal and pelvic surgery
      can lead to such major complications as bowel obstruction or infertility.
      Poly(vinyl alcohol) (PVA) membranes and hydrogels were placed over the injured
      tissue to act as a physical barrier and prevent such adhesions from occurring in
      a rabbit sidewall model. The membranes were sutured into place to prevent their
      slipping or curling on the moist tissue. Various in vitro experiments (including
      testing for swelling and mechanical strength) were conducted in order to better
      understand the behavior of these membranes in the wound. The results showed that
      both the PVA membranes and PVA hydrogels significantly reduced the number and
      severity of adhesions in the rabbit sidewall model, and even indicated a distinct
      improvement over SEPRAFILM as antiadhesion barriers. Contact-angle measurements
      were taken in order to evaluate the surface properties of the membranes and
      hydrogels. Three approaches were taken to render the membranes more bioadhesive,
      and forego the need for future additional suturing: imprinting a texture onto the
      membrane, coating the membrane with carboxy methyl cellulose (CMC), and producing
      bi-layered, porous PVA membranes through a process of lyophilization. Though the
      surface of the PVA hydrogels is more hydrophilic than the surface of the PVA
      membranes, neither would adhere untreated to moist tissue. However, all three
      approaches aimed at improving their bioadhesion yielded excellent results and
      demonstrated that PVA could indeed be considered a viable method of adhesion
      prevention.

PMID- 15264301
TI  - Evidence of octacalcium phosphate and Type-B carbonated apatites deposited on the
      surface of explanted acrylic hydrogel intraocular lens.
AB  - Fourier-transform infrared (FTIR) microspectroscopy combining with attenuated
      total reflection (ATR) microsampling technique and micro-Raman spectrophotometer
      were used to detect the deposited materials on the surface of acrylic hydrogel
      intraocular lens (IOL) with or without ocular implantation. Surface morphology
      and the interface of this IOL were further examined by a confocal laser scanning
      microscope. The brand-new IOL exhibited a very smooth, transparent and
      featureless surface, but the explanted IOL had an irregular cerebriform-like
      opaque appearance. Both FTIR/ATR and Raman microspectroscopic analyses showed the
      deposits on the surface of acrylic hydrogel IOL after ocular implantation to
      consist of octacalcium phosphate (OCP) and Type B carbonated apatites, leading to
      the opalescence of acrylic hydrogel IOL. Both vibrational microspectroscopic
      examinations also confirmed the mineralization still in progress on the surface
      of acrylic hydrogel IOL after ocular implantation for 2 years.

PMID- 15264302
TI  - Biocompatibility and osseointegration of beta-TCP: histomorphological and
      biomechanical studies in a weight-bearing sheep model.
AB  - The aim of the study was to investigate the biocompatibility, degradation, and
      biomechanical properties of beta-TCP (Cerasorb) in a weight-bearing sheep model.
      beta-TCP implant prototypes were implanted in the tibial head of adult merino
      sheep. After 6 and 12 months material explants were harvested for biomechanical,
      histological, and histomorphometrical analysis. Corresponding bone specimens of
      the intact bone of the contralateral leg were used as controls in the
      biomechanical test. Compression tests showed higher values for maximum fracture
      load, yield strength, and compression modulus after 6 and 12 months compared to
      control. Microscopically, the implants showed good osteoconduction and were
      incorporated into the bone; however, relevant amounts of beta-TCP were still
      present after 12 months. Histomorphological results revealed that beta-TCP had
      partially degraded between implantation and 6 months, but its share remained
      constant between 6 and 12 months. The bone volume fraction in the area of the
      implant (46% +/- 6.5%) was initially higher than in the corresponding bone area
      of the contralateral leg (31% +/- 9.6%), but after 12 months declined to 29% +/-
      9.4% (control: 33% +/- 8.3%), while the share of beta-TCP remained constant at
      36% +/- 12.2%. These findings were supported by microradiographic data. In
      conclusion, in a weight bearing implantation model beta-TCP showed good
      biocompatibility, osseointegration and beginning degradation, even though it was
      not further degraded between 6 and 12 months.

PMID- 15264303
TI  - Flexural fatigue behavior of machinable and light-activated hybrid composites for
      esthetic restorations.
AB  - The purpose of this study was to determine the flexural strength and flexural
      fatigue strength of a machinable composite (GN-I) and three hybrid composites
      (Artglass, Estenia, and Gradia). Specimens (2 x 2 x 25 mm) were polymerized in a
      laboratory photo-curing unit and then immersed in water at 37 degrees C for 24 h,
      6 months, and 1 year. After each immersion period, flexural strengths (4-PFS)
      were measured at a cross-head speed of 1 mm/min in 4-point bending (span = 20 mm;
      distance between inside loading points = 10 mm). The cyclic fatigue test was
      performed at 2.0 Hz on a fatigue tester. The staircase method was employed for
      flexural fatigue strength (FFS) using a 5000 cyclic load limitation, 5-MPa stress
      increment, and 20 specimens for each material. Both 4-PFS and FFS of the
      machinable composite after all immersion periods were significantly greater than
      those of the three hybrid composites. The FFS results followed the same pattern
      as those of the 4-PFS. The Estenia material exhibited the highest 4-PFS and FFS
      after 24 h of immersion among three hybrid composites, whereas after 1 year of
      immersion, all three composites showed almost identical 4-PFS and FFS
      statistically. A strong correlation was observed between 4-PFS and FFS of the
      machinable composite and three hybrid resin composites.

PMID- 15264304
TI  - Vascular graft healing. III. FTIR analysis of ePTFE graft samples from implanted
      bigrafts.
AB  - A bigraft, composed of a 30-microm internodal distance expanded
      polytetrafluoroethylene (ePTFE) arterial graft segment and a preclotted
      polyethylene terephthalate arterial graft segment, was used to study the healing
      process of two different materials in the same dog. Healing was followed by FTIR
      ATR spectroscopy and correlated with ELISA analyses of selected growth factors
      and matrix proteins. The FTIR analyses of the ePTFE explants from 1 and 3 h; 3,
      5, 7, 10, and 14 days; and 4 and 8 weeks showed that the ePTFE grafts did not
      heal (endothelialize), but appeared to remain in overlapping inflammation and
      proliferation stages of wound healing. Although FN was found in the fibrin layer
      coating the luminal surface of the ePTFE, VEGF was not present. The inability of
      VEGF to complex with FN may be the result of FN binding sites being blocked or
      hidden by the conformation of the fibrin clot that forms on ePTFE. Also, TGF-beta
      was not present beyond the initial clot formation at 3 h postimplantation. The
      absence of these two growth factors may be an important factor in the lack of
      healing of 30-microm ePTFE grafts, because both were found to be present during
      the early stages of healing for the preclotted polyester grafts that did
      endothelialize.

PMID- 15264305
TI  - Metal-on-metal bearing wear with different swing phase loads.
AB  - There is currently much discussion about the most clinically relevant testing
      methods for evaluating total hip replacements. This study examined the effect of
      different swing phase loads, including microseparation, on the wear, friction,
      and wear particles of metal-on-metal (MOM) hip replacements. MOM hip replacements
      were tested for 5 million cycles with the use of a hip simulator; prostheses were
      tested with a low (100-N) and ISO (280-N) swing phase load, and under
      microseparation conditions. Increasing the swing phase load from 100 to 280 N in
      the same hip simulator increased the wear of the MOM hip replacements by over
      tenfold. Introducing microseparation into the gait cycle increased wear further,
      and stripe wear was observed on the femoral heads, accompanied by corresponding
      rim damage on the acetabular cups. No significant difference in wear particle
      size was observed between wear particles produced by low load and microseparation
      hip simulator conditions. Introducing microseparation into the hip simulator gait
      cycle increased the wear of MOM prostheses. Joint laxity and separation may lead
      to increased wear rates of MOM prostheses in vivo. Additionally elevated positive
      swing phase loads may also increase wear. Variable swing phase load conditions in
      vivo may contribute to variations in clinical wear rates.

PMID- 15264306
TI  - Development of hydroxyapatite bone scaffold for controlled drug release via
      poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings.
AB  - A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated
      with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for
      use as tissue-regeneration and controlled-release system. An antibiotic drug,
      tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating
      layer through a dip-coating and solvent-casting method. Coating cycle and drug
      loading amount differed to control the level of drug-release rate. The HA
      scaffold framework, obtained by a polymeric foam reticulate method, exhibited a
      highly porous structure, with porosity and pore size of approximately 87% and 180
      microm, respectively. The hybrid layer, consisting of PCL sheet and HA fine
      powders, was uniformly coated on the scaffold surface. The coating layer
      exhibited only PCL and HA phases and structures, revealing no chemical
      interaction among the coating components, as observed by X-ray diffraction (XRD)
      and Fourier-transform infrared (FTIR) analyses. The coated-HA scaffolds showed an
      effective stress distribution behavior in response to an applied load, as
      confirmed by the compressive stress-strain curve. The mechanical properties of
      the coated scaffolds were improved highly with coatings; the compressive strength
      and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times,
      and the energy absorption were approximately 8 times, higher than those without
      coating. These improvements were attributed mainly to the shielding of framework
      flaws by a flexible coating layer and partially to the thicker stems (porosity
      reduction). The dissolution of the coated scaffolds in a phosphate-buffered
      saline (PBS) solution increased with incubation time. The drug was released
      sharply within the initial several hours ( approximately 2 h), but the rate
      decreased further, showing a sustained release. The release amount was well
      controlled via coating-cycle and initial drug loading amount, suggesting the
      effectiveness of the coating-scaffold design as a drug-delivery system.

PMID- 15264307
TI  - Osteoblast-like cell response to bioactive composites-surface-topography and
      composition effects.
AB  - Two bioactive composites, containing 40 vol % filler in high-density polyethylene
      (HDPE), were investigated to examine the effects of different filler compositions
      and different surface patterning. The first composite, known as HAPEX, consists
      of hydroxyapatite within HDPE, and the second composite, known as AWPEX, consists
      of glass-ceramic apatite-wollastonite in HDPE. Surface topography effects at 5-50
      and 100-150 microm were explored, with cell morphology analyzed with the use of
      scanning electron microscopy and confocal laser scanning microscopy (CLSM).
      Biochemical assays of adenosine triphosphate and alkaline phosphatase were used
      to analyze osteoblast-like cell proliferation and differentiation. For both
      composites, cell alignment was seen along grooves, pillars, and wells, with
      preferential cell attachment to ceramic particles within the polymer matrices.
      HAPEX showed significantly increased cell proliferation over AWPEX (P < 0.005).
      However, greater cell differentiation occurred for AWPEX over HAPEX (P < 0.005).
      Polishing significantly increased osteoblast-like cell response over as-cut
      samples, but surface-topography changes above 50 microm had no consistent effect.
      Smaller-scale features also showed no significant trend in terms of cell
      proliferation, but did show significant differences in cell differentiation (P <
      0.05). CLSM imaging of actin and vinculin localization within cells showed the
      greatest change in comparison to polished surface controls for cells cultured on
      samples with surface features below 50 microm. The fact that similar observations
      were made for both HAPEX and AWPEX indicated that, for these experiments, the
      effects of surface topography more strongly influenced cell response than
      chemical composition.

PMID- 15264308
TI  - Variation in surface texture measurements.
AB  - Surface texture influences cellular response to implants, implant wear, and
      fixation, yet measurement and reporting of surface texture can be confusing and
      ambiguous. Seven specimens of widely different surface textures were submitted to
      three internationally renowned laboratories for surface texture characterization.
      The specimens were from dental implants, orthopedic implants, and femoral heads.
      Areas to be measured were clearly marked; simplified instructions were supplied
      but specific measurement parameters were not requested. Techniques used included
      contact profilometry, two- and three-dimensional laser profilometry, and atomic
      force microscopy. Four to thirteen parameters were reported, 2D or 3D, including
      R(a) or S(a); only three were common to all centers. The results varied by as
      much as +/-300-1000%, depending on technique and surface type. Some surfaces were
      not measurable by some techniques. One dental implant surface was reported with
      R(a) of 0.17, 0.85, 1.9, and 4.4 microm. The CoCr femoral head ranged from an
      R(a) of 0.011 to 0.10 microm; the zirconia head from 0.006 to 0.05 microm.
      Similar variability was reported for the other parameters. Useful surface texture
      characterization requires reporting of all measurement parameters. Comparisons
      between studies may be compromised if differences in technique are not
      considered.

PMID- 15264309
TI  - Hard-tissue-engineered zirconia porous scaffolds with hydroxyapatite sol-gel and
      slurry coatings.
AB  - A zirconia (ZrO(2)) porous scaffold was coated with a gradient apatite layer to
      induce osteoconductivity with the use of a combination of sol-gel and powder
      slurry methods. The ZrO(2) was used to impart mechanical strength and the apatite
      layer was coated for functional biocompatibility. The coating layer, from the
      outside in, was composed of sol-gel hydroxyapatite (HA)/slurry HA/slurry FA. The
      sol-gel coating powder had a lower crystallinity than the slurry coating powder.
      The sol-gel HA coating over the HA/FA slurry coating layer made the surface very
      smooth. The sol-gel coating over the slurry coating layer enhanced the bonding
      strength up to 33 MPa. The dissolution rate of the sol-gel/slurry coating layer
      was much higher than that of the slurry coating. Moreover, the rate could be
      controlled by altering the heat-treatment temperature of the sol-gel HA layer.
      The MG63 cells cultured on these materials grew and spread in a different manner,
      depending on the coating layer. However, the proliferation rates of the cells on
      both coating systems were not much different.

PMID- 15264310
TI  - Molecular orientation of ultrahigh molecular weight polyethylene induced by
      various sliding motions.
AB  - Wear and wear debris of ultrahigh molecular weight polyethylene (UHMWPE) in joint
      replacements have been recognized as one of the major contributors to the failure
      of orthopedic implants. The detailed wear mechanism of polyethylene under
      biomechanic motions is not well understood. In simulation wear bench tests, it
      was found that unidirectional sliding produces the least amount of wear,
      reciprocating motion increases wear significantly, and cross-shear motion
      (similar to hip and knee joint motion in the human body) produces the highest
      amount of wear. Conventional wear theories are inadequate to explain this
      observation. This study utilizes resonant absorption of linearly polarized soft X
      rays at a synchrotron radiation beam line to measure the molecular orientation of
      a UHMWPE surface layer subjected to different wear motions. Carbon-K-edge partial
      electron-yield X-ray absorption measurements were done on the worn UHMWPE
      samples. X-ray absorption measurements show conclusively that the molecular
      chains of UHMWPE align preferentially parallel to the direction of sliding.
      Examination under various wear motions showed that unidirectional shear produced
      the maximum chain orientation, whereas cross-shear wear motions produced the
      least amount of orientation. When polymeric chains align, the surface layer tends
      to be more brittle and hard, thus resisting wear. When they do not align, loose
      chains may be subjected to both Mode I and Mode II fracture, hence increasing the
      wear rate. This molecular alignment observation may offer an explanation of why
      different wear motions have different wear characteristics.

PMID- 15264311
TI  - Bioresorbable nanofiber-based systems for wound healing and drug delivery:
      optimization of fabrication parameters.
AB  - Wound healing is a complex process that often requires treatment with
      antibiotics. This article reports the initial development of a biodegradable
      polymeric nanofiber-based antibiotic delivery system. The functions of such a
      system would be (a) to serve as a biodegradable gauze, and (b) to serve as an
      antibiotic delivery system. The polymer used in this study was poly(lactide-co
      glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the
      electrospinning process. The objective of this study was to determine the effect
      of fabrication parameters: orifice diameter (needle gauge), polymer solution
      concentration, and voltage per unit length, on the morphology and diameter of
      electrospun nanofibers. The needle gauges studied were 16 (1.19 mm), 18 (0.84
      mm), and 20 (0.58 mm), and the range of polymer solution concentration studied
      was from 0.10 g/mL to 0.30 g/mL. The effect of voltage was determined by varying
      the voltage per unit electrospinning distance, and the range studied was from
      0.375 kV/cm to 1.5 kV/cm. In addition, the mass per unit area of the electrospun
      nanofibers as a function of time was determined and the feasibility of antibiotic
      (cefazolin) loading into the nanofibers was also studied. The results indicate
      that the diameter of nanofibers decreased with an increase in needle gauge
      (decrease in orifice diameter), and increased with an increase in the
      concentration of the polymer solution. The voltage study demonstrated that the
      average diameter of the nanofibers decreased with an increase in voltage.
      However, the effect of voltage on fiber diameter was less pronounced as compared
      to polymer solution concentration. The results of the areal density study
      indicated that the mass per unit area of the electrospun nanofibers increased
      linearly with time. Feasibility of drug incorporation into the nanofibers was
      demonstrated with the use of cefazolin, a broad-spectrum antibiotic. Overall,
      these studies demonstrated that PLAGA nanofibers can be tailored to desired
      diameters through modifications in processing parameters, and that antibiotics
      such as cefazolin can be incorporated into these nanofibers. Therefore, PLAGA
      nanofibers show potential as antibiotic delivery systems for the treatment of
      wounds.

PMID- 15264312
TI  - Induction of cyclooxygenase-2 mRNA and protein expression by dentin bonding
      agents in human gingival fibroblasts.
AB  - An ideal dentin bonding agent should be nonirritating to surrounding tissues.
      Unfortunately, all histological investigations have demonstrated that dentin
      bonding agents can induce mild to severe inflammatory alterations. However, there
      is little information on the precise mechanisms about dentin bonding agents
      induced inflammatory reaction. Cyclooxygenase-2 (COX-2) is an inducible enzyme
      believed to be responsible for prostaglandin synthesis at the site of
      inflammation. The aim of the present study was to investigate the effects of
      three dentin bonding agents, Clearfil SE Bond, Prime & Bond NT, and Single Bond
      on the expression of COX-2 mRNA gene and protein in cultured human gingival
      fibroblasts. The exposure of quiescent human gingival fibroblasts to dentin
      bonding agents resulted in the induction of COX-2 mRNA expression. The
      investigations of the time-dependent on COX-2 mRNA expression in dentin bonding
      agent-treated human gingival fibroblasts revealed different patterns. The
      influence of COX-2 mRNA depended on the tested materials. In addition, all dentin
      bonding agents also induced COX-2 protein expression in human gingival
      fibroblasts. Taken together, the activation of COX-2 expression may be one of the
      potential mechanisms of dentin bonding agent-induced gingival inflammation.

PMID- 15264313
TI  - Experimental assessment of new stent technologies: validation of a comparative
      paired rabbit iliac artery study model.
AB  - Preventing coronary in-stent restenosis is a major challenge for physicians and
      industry. To assess new stent technologies, a comparative paired iliac artery
      model in rabbits is proposed. One tubular stent was implanted in each external
      iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of
      20% was strictly observed. Restenosis was examined at 30 days by angiography,
      intravascular ultrasound (IVUS) examination, and histomorphometry. On
      quantitative angiography, the mean loss of angiographic diameter was 9.8 +/- 4.4%
      in the right as compared to 9.3 +/- 55% in the left artery (p = 0.75). On IVUS,
      the volume of intrastent neointimal proliferation was 26.6 +/- 4.9 mm(3) in the
      right and 25.8 +/- 3.5 mm(3) in the left artery (p = 0.58). In histomorphometry,
      the neointimal proliferation area was 0.78 +/- 17 mm(2) in the right and 0.76 +/-
      0.17 mm(2) in the left artery (p = 0.87). Intrastent neointimal proliferation was
      comparable between the left and right arteries of all rabbits. The model has
      three main advantages: (1) arterial dilatation and thus arterial wall aggression
      are controlled, (2) pairing makes each animal its own control subject, and (3)
      the statistical power for comparative testing is maximized. The model enables the
      effect of a new drug-delivery device to be assessed.

PMID- 15264314
TI  - 3D microtomographic characterization of precision extruded poly-epsilon
      caprolactone scaffolds.
AB  - One of the dominant approaches to tissue engineering is the seeding of
      biodegradable, biocompatible polymer scaffolds with progenitor cells prior to 3D
      culture or implantation. The microarchitecture of these scaffolds has direct
      effects upon the ability of cells to attach, migrate, and differentiate.
      Microtomographic (micro-CT) scanners enable high-speed 3D characterization of the
      salient features of these polymer scaffolds. A micro-CT scan followed by 3D
      reconstruction of serial image sections can determine porosity, pore size, pore
      interconnectivity, strut size, and overall 3D microarchitecture. In this study,
      four polymer samples with different microarchitectures were manufactured through
      precision extrusion deposition free-form fabrication and subsequently
      characterized through micro-CT analysis. A desktop micro-CT scanner was used to
      examine each sample at approximately 19.1-micron resolution. 2D analyses and 3D
      reconstructions of core regions of each sample were performed. These results
      illustrate that qualitative and quantitative analysis of polymer scaffolds is
      possible using micro-CT and 3D reconstruction techniques.

PMID- 15264315
TI  - Electrochemical properties of suprastructures galvanically coupled to a titanium
      implant.
AB  - In recent years, dental implants have been widely used for the aesthetic and
      functional restoration of edentulous patients. Dental implants and restorative
      alloys are required with high corrosion resistance. Suprastructures and implants
      of different compositions in electrical contact may develop galvanic or coupled
      corrosion problems. In addition to galvanic corrosion, crevice and pitting
      corrosion may occur in the marginal gap between dental implant assemblies. In
      this study, gold, silver-palladium, cobalt-chromium, and nickel-chromium
      suprastructures were used to investigate their galvanic and crevice corrosion
      characteristics in combination with titanium (Ti) implants. Potentiodynamic and
      potentiostatic testing were performed in artificial saliva at 37 degrees C.
      Potentiodynamic testing was carried out at the potential scan rate of 1 mV/s in
      the range of -600-1600 mV (SCE). Potentiostatic testing was performed with an
      open-circuit potential and current densities at -250, 0, and 250 mV (SCE) in
      artificial saliva. After electrochemical testing, surface morphologies and cross
      sections were examined using micrographs of the samples. Potentiodynamic test
      results indicated that suprastructure/Ti implant couples produced passive current
      densities in the range of 0.5-12 microA/cm(2); Ti abutment/Ti implant and gold/Ti
      implant couples exhibited relatively low passive current densities; Co-Cr/Ti
      implant couples the highest. Co-Cr and Ni-Cr/Ti implant couples showed breakdown
      potentials of 700 and 570 mV (SCE), respectively. The open-circuit potentials of
      silver, Ti abutment, gold, Ni-Cr, and Co-Cr/Ti implant couples were -93.2 +/-
      93.9, -123.7 +/- 58.8, -140.0 +/- 80.6, -223.5 +/- 35.1, and -312.7 +/- 29.8 mV
      (SCE), respectively, and did not change with immersion time. The couples
      exhibited cathodic current densities at -250 mV (SCE); in particular, gold and
      silver alloys showed high cathodic current densities of -3.18 and -6.63
      microA/cm(2), respectively. At 250 mV (SCE), Ti abutment/Ti implant couples
      exhibited a minimum current density of 9.48 x 10(-2) microA/cm(2), but gold, Ni
      Cr, Co-Cr, and silver/Ti implant couples exhibited 0.313, 1.27, 5.60, and 8.06
      microA/cm(2), respectively. All couples exhibited relatively low current
      densities at 0 mV (SCE). Photomicrographs after electrochemical testing showed
      crevice or pitting corrosion in the marginal gap and at the suprastructure
      surface. Although of the tested samples Co-Cr/Ti implant couples showed the
      possibility of galvanic corrosion, its degree was not significant. However, it
      should be borne in mind that galvanic corrosion can accelerate localized
      corrosion, such as crevice or pitting corrosion.

PMID- 15264316
TI  - High release of antibiotic from a novel hydroxyapatite with bimodal pore size
      distribution.
AB  - We developed a novel hydroxyapatite (HA) cylinder (HA-A) and compared the slow
      release of antibiotic in vitro as well as osteoconduction of the material in vivo
      to a commercially produced porous hydroxyapatite cylinder (HA-B). HA-A (4 x 4 mm)
      was synthesized by mixing HA powder, gelatin, and vegetable oil. The material had
      a bimodal pore size distribution, with intragranular (10 nm to 10 microm) and
      intergranular (100 microm) pores, and porosity of 40 vol %, while HA-B had pore
      sizes ranging from 50 to 300 microm and identical porosity. In vitro drug release
      was tested using antibiotics (isepamicin sulfate, vancomycin hydrochloride, and
      flomoxef sodium) soaked on the HA cylinders using a vacuum system. The mean
      adsorption efficiency was higher for HA-A (46%) than for HA-B (26%) and higher
      levels of antibiotic were released from HA-A. Of the antibiotics, ISP showed the
      longest release duration. Bone ingrowth into the pores was observed for both
      materials. Because the novel HA showed both the slower release of antibiotic
      (nanosize pores) and supported excellent osteoconduction (microsize pores), it
      could be useful for the treatment of osteomyelitis.

PMID- 15264317
TI  - Mechanical characterization of self-curing acrylic cements formulated with
      poly(methylmethacrylate)/poly(epsilon-caprolactone) beads.
AB  - New acrylic-based cements were formulated by replacing a mass fraction of 20% of
      poly(methyl methacrylate) (PMMA) powder by PMMA/poly(epsilon-caprolactone) (PCL)
      beads (throughout this article all compositions are given as mass fractions,
      unless specified otherwise). PMMA/PCL beads containing 10 and 30% PCL were
      synthesized by suspension polymerization. Cements were prepared by replacing part
      of the PMMA powder of the formulation by an equivalent mass of PMMA/PCL
      particles. The influence of the PCL content in the beads on the mechanical
      behavior was assessed by testing the cements in flexure and compression. The
      addition of PMMA/PCL particles with 10% PCL content resulted in a marked increase
      in both flexural modulus and flexural strength related to the plain PMMA beads
      formulation. This improvement was attributed to a decrease in the cured material
      porosity. Conversely, by the incorporation of beads with 30% PCL content the
      flexural properties decreased. This behavior was attributed to the debonding of
      the particles from the matrix, which was revealed by SEM images. The observed
      compressive yield strength decrease with the increase of PCL content in the beads
      was attributed to a low degree of adhesion between the heterogeneous particles
      and the matrix as well as to the plasticizing effect of the PCL.

PMID- 15264318
TI  - Vascular response to titanium dioxide: a study on the rat carotid artery.
AB  - The purpose of this study was to explore the effects of titanium dioxide (TiO(2))
      on vascular smooth muscle contractility with the use of the rat carotid-artery
      model. TiO(2) powder was implanted on right carotid arteries of five albino rats,
      the left arteries of which were left intact and served as controls. Fourteen days
      after placement, bilateral carotid arteries were removed and
      contraction/relaxation of isolated vessel rings were measured for dose-dependent
      epinephrine and acetylcholine administrations by a force displacement transducer.
      The data of each tissue specimen were collected with the use of a computerized
      system and corresponding software at a sample rate of 1000 kHz, and were
      expressed as contraction force. Contraction forces of control and TiO(2)
      implanted vessel rings were similar (P > 0.05). TiO(2) does not appear to have
      adverse effects on vascular contractility.

PMID- 15264319
TI  - Bone cement X-ray contrast media: a clinically relevant method of measuring their
      efficacy.
AB  - It is important to compare different contrast media used in bone cement according
      to their ability to attenuate X-rays and thereby produce image contrast between
      bone cement and its surroundings in clinical applications. The radiopacity of
      bone cement is often evaluated by making radiographs of cement in air at an X-ray
      tube voltage of 40 kV. We have developed a method for ranking contrast media in
      bone cement simulating the clinical situation, by (1) choosing the same X-ray
      tube voltage as used in clinical work, and (2) using a water phantom to imitate
      the effects of the patients' soft tissue on the X-ray photons. In clinical work
      it is desirable to have low radiation dose, but high image contrast. The voltage
      chosen is a compromise, because both dose and image contrast decrease with higher
      voltage. Three contrast media (ZrO(2), BaSO(4), and Iodixanol) have been compared
      for degree of "image contrast." Comparing 10 wt % contrast media samples at an X
      ray tube voltage of 40 kV, ZrO(2) produced higher image contrast than the other
      media. However, at 80 kV, using a water phantom, the results were reversed,
      ZrO(2) produced lower image contrast than both BaSO(4) and Iodixanol. We conclude
      that evaluations of contrast media should be made with voltages and phantoms
      imitating the clinical application.

PMID- 15264320
TI  - Engineered allogeneic chondrocyte pellet for reconstruction of fibrocartilage
      zone at bone-tendon junction--a preliminary histological observation.
AB  - This study examined histologically the potential of using allogeneic cultured
      chondrocyte pellet (CCP) in enhancing bone-tendon junction (BTJ) healing using a
      rabbit partial patellectomy model. Chondrocytes isolated from the cartilaginous
      ribs of 6-week-old New Zealand white rabbits were cultured for 14 days to form
      CCP. Partial patellectomy was performed on 30 18-week-old rabbits. After removal
      of the distal third patella, the BTJ gap was repaired surgically with or without
      CCP interposition. Four samples of patella-patellar tendon complexes (PPTC) for
      each group were harvested each at 8, 12, and 16 weeks; and two additional PPTC
      for each group were harvested at 2, 4, and 6 weeks for early observation of
      fibrocartilage zone regeneration, histologically. Results showed that CCP
      interposition demonstrated earlier structural integration at the BTJ after 8, 12,
      and 16 weeks of healing, and formation of a fibrocartilage zone like structure,
      compared with control specimens. In addition, no immune rejection was observed in
      CCP experimental group. The results suggested that CCP had a stimulatory effect
      on BTJ healing. This bioengineering approach might have potential clinical
      application in treatment of difficult BTJ healing. However, systemic
      histomorphometric, immunological tests, and biomechanical evaluations are needed
      before any clinical trials.

PMID- 15264322
TI  - Surface modifications of alumina-silica glass fiber.
AB  - A commercial glass fiber with Al(2)O(3) (68.4%) and SiO(2) (27.6%) as major
      components and CaO, TiO(2), Fe(2)O(3), and CuO as minor components was used as
      substrate in a silica sol-gel coating process. After cleaning, fiber samples were
      immersed into tetraethoxysilane (TEOS) at room temperature for 1 h, and then
      individual fiber samples were soaked into a simulated body fluid (SBF) solution,1
      and removed after 5, 10, 15, and 20 days. Zeta potential and Energy Dispersive
      Spectroscopy (EDS) analyses showed that the fiber surfaces were effectively
      coated with a silica layer, which improved the formation of an HA layer upon
      immersion into SBF solution for 5 days. The coating became even more continuous
      after 10-day immersion. Fourier Transform Infrared Spectroscopic (FTIR) analyses
      confirmed that the coating layer has P--O vibration bands characteristic of
      hydroxyapatite (HA) near 1060 and 600 cm(-1).

PMID- 15264321
TI  - The behavior of novel hydrophilic composite bone cements in simulated body
      fluids.
AB  - Composite bone cements were formulated with bioactive glass (MgO--SiO(2)--3CaO.
      P(2)O(5)) as the filler and hydrophilic matrix. The matrix was composed of a
      starch/cellulose acetate blend (SCA) as the solid component and a mixture of
      methylmethacrylate/acrylic acid (MMA/AA) as the liquid component. The curing
      parameters, mechanical properties, and bioactive behavior of these composite
      cements were determined. The addition of up to 30 wt % of glass improved both
      compressive modulus and yield strength and kept the maximum curing temperature at
      the same value presented by a typical acrylic-based commercial formulation. The
      lack of a strongly bonded interface (because no coupling agent was used) had
      important effects on the swelling and mechanical properties of the novel bone
      cements. However, bone cements containing AA did not show a bioactive behavior,
      because of the deleterious effect of this monomer on the calcium phosphate
      precipitation on the polymeric surfaces. Formulations without AA were prepared
      with MMA or 2-hydroxyethyl methacrylate (HEMA) as the liquid component. Only
      these formulations could form an apatite-like layer on their surface. These
      systems, therefore, are very promising: They are bioactive, hydrophilic,
      partially degradable, and present interesting mechanical properties. This
      combination of properties could facilitate the release of bioactive agents from
      the cement, allow bone ingrowth in the cement, and induce a press-fitting effect,
      improving the interfaces with both the prosthesis and the bone.

PMID- 15264323
TI  - Effect of molar mass of an experimental primer on shear bond strength to dentin.
AB  - A novel oligomer was synthesized in different molecular masses and used as a
      primer in dentin bonding. The hypothesis was that an intermediate molecular mass
      would optimize the conflicting needs for diffusion into etched dentin (low M(w))
      and high mechanical properties (high M(w)). The initial oligomer synthesized was
      tert butylmethacrylate-co-maleic anhydride, which was further reacted to add
      hyrdoxyethyl methacrylate (HEMA) across the anhydride. The oligomer was
      synthesized in a series of molecular masses from approximately 800-6000 amu. The
      oligomer with an average M(w) of approximately 1000 amu provided the highest bond
      strength (16 MPa), with both lower and higher molar mass oligomers producing
      lower bond strengths. A polynomial model was fitted to the data with an R(2) =
      0.606, while a linear model only had an R(2) = 0.534. This implies that the graph
      of molar mass to bond strength has a maximum in the range of molar masses
      examined, and that an optimum molar mass can be found between 800 and 6000 amu.

PMID- 15264324
TI  - Improved collagen bilayer dressing for the controlled release of drugs.
AB  - A novel bilayer dressing has been developed from bovine succinylated collagen.
      The dressing contains an antibiotic, Ciprofloxacin, for both immediate and time
      regulated release for controlling the infection, as the infected open wounds need
      special care. The dressing consists of a sponge and a film, both prepared from
      succinylated bovine collagen. The sponge has a smooth surface on one side; its
      rough surface on the other side forms the bilayer system with the film. Both
      sponge and film act as an anionic reservoir to hold the cationic Ciprofloxacin.
      The drug, after dispersing in poly (N-vinyl-2-pyrrolidione) (PVP) solution is
      allowed to spread in the bilayer system by diffusion. The drug stays in the
      bilayer system because of ionic binding, but starts releasing when comes in
      contact with the wound. Release of the drug is immediate, but it is regulated by
      ionic binding between the drug and succinylated collagen. The wound exudates, and
      there is a polarity-controlled release of the drug from the bilayer system. The
      PVP and bilayer system permits only time-regulated release, and the system lasts
      up to 5 days with therapeutically sufficient drug availability.

PMID- 15264325
TI  - Molecular diffusion in tissue-engineered cartilage constructs: effects of
      scaffold material, time, and culture conditions.
AB  - Diffusion is likely to be the primary mechanism for macromolecular transport in
      tissue-engineered cartilage, and providing an adequate nutrient supply via
      diffusion may be necessary for cell proliferation and extracellular matrix
      production. The goal of this study was to measure the diffusivity of tissue
      engineered cartilage constructs as a function of scaffold material, culture
      conditions, and time in culture. Diffusion coefficients of four different-sized
      fluorescent dextrans were measured by fluorescence recovery after photobleaching
      in tissue-engineered cartilage constructs seeded with human adipose-derived stem
      cells or acellular constructs on scaffolds of alginate, agarose, gelatin, or
      fibrin that were cultured for 1 or 28 days in either chondrogenic or control
      conditions. Diffusivities in the constructs were much greater than those of
      native cartilage. The diffusivity of acellular constructs increased 62% from Day
      1 to Day 28, whereas diffusivity of cellular constructs decreased 42% and 27% in
      chondrogenic and control cultures, respectively. The decrease in diffusivity in
      cellular constructs is likely due to new matrix synthesis, which may be enhanced
      with chondrogenic media, and matrix contraction by the cells in the fibrin and
      gelatin scaffolds. The increase in diffusivity in the acellular constructs is
      probably due to scaffold degradation and swelling.

PMID- 15264327
TI  - Anecdotal history Middlesex University School of Veterinary Medicine.

PMID- 15264326
TI  - Influence of cross-linked PMMA beads on the mechanical behavior of self-curing
      acrylic cements.
AB  - Cross-linked PMMA beads were prepared with the use of two cross-linking agents
      with different chain lengths: triethylene glycol dimethacrylate (TEGDMA) and
      poly(ethylene glycol) dimethacrylate (PEGDMA). Beads containing 10 wt % TEGDMA
      and 2, 5, and 10 wt % PEGDMA were synthesized by suspension polymerization.
      Experimental cement formulations were prepared by replacing part of the PMMA
      powder phase by an equivalent weight of the cross-linked beads. The mechanical
      behavior of the modified cements was carried out by testing the cements in
      flexure and compression. All cements displayed a higher flexural modulus, which
      was accompanied with a slight decrease in the flexural strength. The two
      parameter Weibull model, which was used to analyze the flexural strength data,
      gave a good representation of the fracture load distribution. In cements prepared
      with beads containing 2 and 5 wt % PEGDMA and 10 wt % TEGDMA, no improvement in
      the flexural strength was observed. Debonding of the particles from the matrix
      was considered responsible for the decreased flexural strength. On the contrary,
      cements prepared with different proportions of beads containing 10 wt % PEGDMA
      resulted in a markedly increased flexural strength compared with the unmodified
      cement. An improved reinforcing effect of the cross-linked beads and a
      significant degree of bonding with the matrix in these cements account for the
      superior flexural strength compared with the other composite cements tested.

PMID- 15264329
TI  - Bibliography. Current world literature. Breast.

PMID- 15264328
TI  - [Filaria of the lymphatic system: Wuchereria, Brugia].

PMID- 15264330
TI  - Bibliography. Current world literature. Therapeutic modalities.

PMID- 15264331
TI  - Bibliography. Current world literature. Gynecologic cancer.

PMID- 15264332
TI  - Neurooncology--present and future.

PMID- 15264333
TI  - Forgotten veterinarians 1. Harry Hart and Pancho Villa.

PMID- 15264335
TI  - 2. Countess von Maltzan was a veterinarian.

PMID- 15264334
TI  - Food and fluid intake and disturbances in gastrointestinal and mental function
      during an ultramarathon.

PMID- 15264336
TI  - Dueling serpents.

PMID- 15264337
TI  - Animal therapy over the ages: 11. Zoogenous therapy. Frogs, toads, insects, eggs.

PMID- 15264338
TI  - 12. Magnets and massage.

PMID- 15264339
TI  - [Pharmacists as pioneers in porcelain production: what the service, Flora Danica
      owe to the Bordeaux's apothecary Marc-Hilaire Vilaris].
AB  - In 1766, The Bordeaux's apothecary Marc-Hilaire Vilaris (1719-1792) identified
      with certainty a kaolin's deposit at Saint-Yrieix, in the country of Limousin,
      allowing so the porcelain manufacture in France and the development of a china
      clay's and porcelain's dough trade. Archives documents give evidence of regularly
      supplies of limousin's raw materials by the pharmacist Frantz Heinrich Muller
      (1732-1820), Director of the Royal china's Manufactury of Denmark, some time
      before production of the famous table service Flora Danica.

PMID- 15264340
TI  - [The history of the approval of an anthelminthic syrup by the " Societe royale de
      medicine" at the end of the 18th century].
AB  - A dossier in the archives of the Academie nationale de medecine made possible a
      description of the course of events in obtaining an approval of an anthelmintic
      syrup by the Societe royale de medicine. The pharmacists Lanoix and Macors of
      Lyon founded a society in 1778 together with Greth, a non pharmacist, with the
      intention of exploiting in their sole names a syrup which he elaborated. In 1780
      they request the Societe royale de medicine a privilege for seling the syrup
      which was refused. After this unsuccessful attempt Greth however continued his
      efforts and obtained an approval in 1787. He sollicited even the kind protection
      of the minister in 1788. The documents demonstrate the impartiality and
      seriousness of the members of the Societe royale and the not always orthodox
      procedures of the applicants.

PMID- 15264341
TI  - Elderly people's accounts of home care rationing: missing voices in long-term
      care policy debates.
AB  - Fundamental shifts in state intervention in recent years have resulted in steady
      curtailment in public provision of community and social care. A longitudinal
      study of elderly women receiving home care in Ontario explored the reverberations
      of these shifts in the texture of frail elderly people's lives. Three distinct
      accounts of negotiating unstable and rationed home care were discernible. "Taking
      charge" was an active account of women successfully impressing their particular
      needs and identities on home care provision. "Pushed over the edge" was a
      vulnerable account of insufficient and depersonalized care in which participants
      felt themselves practically and emotionally out of control. In "Restraining
      expectations", women adjusted silently to the shortcomings of home care,
      stoically making themselves smaller as they found their previous orbits and
      identities unsupported. Home care's front line emerged as a complex site of
      struggle for identity and agency--a struggle in which elderly people engage with
      inventiveness and determination but also with dwindling support, few witnesses
      and in mounting isolation.

PMID- 15264343
TI  - A national neuroimaging database: a call to action.

PMID- 15264342
TI  - Ethics of assertive outreach (assertive community treatment teams).
AB  - PURPOSE OF REVIEW: Assertive outreach, also known as assertive community
      treatment, is a well established service model in several countries for people
      with severe and enduring mental health problems who do no engage with psychiatric
      services. However, it has been criticized for being coercive and paternalistic.
      The present review considers a number of recent contributions to the debate
      concerning the ethics of assertive outreach. RECENT FINDINGS: Assertive outreach
      brings into sharp focus a number of ethical issues that affect most mental health
      services, but it also generates new ones, primarily whether delivery of a service
      to people who are refusing it and are not legally bound to accept it can be
      justified. Several authors have grappled with these issues, mainly through using
      traditional principles of ethical treatment based on professional values, and
      this paper reviews such attempts at resolving those dilemmas. In so doing, it
      reveals the limitations of such approaches. SUMMARY: In conclusion, the present
      review suggests an alternative ethical basis for supporting delivery of assertive
      outreach services to a reluctant client group, which focuses more on the client's
      values and areas of assistance with which they express genuine appreciation and
      satisfaction.

PMID- 15264344
TI  - Psychosis: conceptual and ethical aspects of early diagnosis and intervention.
AB  - PURPOSE OF REVIEW: Interest in the early identification and treatment of
      incipient first-episode psychosis is rapidly expanding. In the present review we
      discuss the major conceptual and ethical problem areas related to research and
      clinical work in detection and treatment of prepsychosis. RECENT FINDINGS: The
      recent literature shows that conceptualization of early psychosis is often
      inconsistent and even misleading. Ethical discussions mostly concern 'false
      positives' risk assignments, stigmatization, informed consent and acceptability
      of treatment procedures. SUMMARY: At present there is a lack of consensus
      regarding which concepts to use in describing prepsychosis in prospective
      studies, and new concepts are needed for prospective description of emergent
      psychosis.

PMID- 15264345
TI  - [Biographical notes on Pierre Cheri Grimaux, Marine pharmacist, professor at the
      Rochefort's School of Navy Health (1795-1860)].
AB  - Born on the Directoire, engaged as ship-boy in Navy, injured, demobilized,
      engaged in Army as far as the end of Cent Jours, starts again his studies at the
      Rochefort's School of Navy Health, he finished his career as chief-pharmacist
      professor in 1852. He died at Rochefort in 1860, Father of Edouard Grimaux, he
      influenced the career choice of his son toward chemistry with the success and
      notoriety as we know.

PMID- 15264346
TI  - Acrylamide toxicities and food safety: Session IV summary and research needs.

PMID- 15264347
TI  - [The pharmacist Leopold Mathet and the photography].
AB  - From 1872 and during half-century , the pharmacist Leopold Mathet (1850-1922) was
      interested in theoretical and practical faces of photography whose he was a
      talented popularizer by means of his many books and publications. He specially
      got enthusiastic over colour photography by additive trichromy and he made
      sensitized plates including polychromatic net which, as early as 1904, he
      achieved successfully fine colour photographs.

PMID- 15264349
TI  - [Drugs under temporary use authorisation: 50 years of French drug development].
AB  - Drug under temporary use authorisation (authorisation temporaire d' utilisation -
      ATU) was created in 1994 in France. Before this date, various procedures
      controlled patients' use of imported drug and drug in process. The AIDS pandemy
      development in 80's and the need to control news drugs patients' use contributed
      to the ATU statement setting up. This regulatory statement allows companies to
      sell drugs without market drug authorisation (autorisation de mise sur le marche 
      AMM), the letter being done in adequation with good pharmaceutical quality and a
      satisfactory level of benefices/ risks ratio. It's a recent French drug
      evaluation evolution.

PMID- 15264348
TI  - Superior gluteal nerve: safe area in hip surgery.
AB  - Injuries to the superior gluteal nerve are very bad complications in hip surgery.
      An exact knowledge of its course may be helpful in avoiding such problems.
      Nineteen half pelvises from ten male and female adult cadavers were dissected.
      Dissections revealed that the nerve divided into two (89.48%) or three (10.52%)
      branches after leaving the pelvis. The more caudal branch was responsible for
      innervation of tensor fascia latae. The distance and the angle from the entry
      points of all branches of the superior gluteal nerve into the deep surface of the
      gluteus medium and minimus muscles to the mid-point of the superior border of the
      greater trochanter were measured. The branch that innerved the tensor fascia
      latae was also followed. These data were subjected to several statistical tests.
      Based on these findings, and in order to prevent nerve damage, we propose to
      define a 2-3 cm safe area above the great trochanter.

PMID- 15264350
TI  - Infant and child neurotoxicity studies: subtle and long-term effects.

PMID- 15264351
TI  - Training our future rural medical workforce.

PMID- 15264352
TI  - Britain's brain gain.

PMID- 15264353
TI  - Chemical danger.

PMID- 15264354
TI  - High risk of nosocomial-acquired RSV infection in children with congenital heart
      disease.

PMID- 15264355
TI  - Alan Trounson, Scientific Director of Monash IVF, Australia.

PMID- 15264356
TI  - Causes of infant mortality at night.

PMID- 15264358
TI  - Children in foster and kinship care at risk for inadequate health care coverage
      and access.

PMID- 15264359
TI  - Public health: when the talking has to stop.

PMID- 15264357
TI  - Safety net "crowding out" private health insurance for childless adults.
AB  - Because so many low-income children are eligible for either Medicaid or the State
      Children's Health Insurance Program, even when they access safety-net providers,
      the doctors can usually get them enrolled in the appropriate program.

PMID- 15264360
TI  - Primary care ideas. Entrepreneurial spirit.

PMID- 15264361
TI  - Poland's broken promises.

PMID- 15264362
TI  - Variation in torque expression.

PMID- 15264363
TI  - The divine proportion.

PMID- 15264364
TI  - Invisalign and changing relationships.

PMID- 15264365
TI  - On location North Central London. Political futures at stake in key service
      reviews.

PMID- 15264366
TI  - Primary care ideas. Three cheers for PCTs.

PMID- 15264367
TI  - 2003 Keio Medical Science Prize commemorative lecture. PPARs and the complex
      journey to obesity.

PMID- 15264368
TI  - 2003 Keio Medical Science Prize commemorative lecture. Neural mechanisms of
      cognitive memory.

PMID- 15264369
TI  - Frank P. Bowyer, 1917-2004.

PMID- 15264370
TI  - [Pharmacy students proceeding from Alsace and Moselle to Nancy between 1872 and
      1914].
AB  - Because of the war against Prussia, the school of pharmacy of Strasbourg was
      transfered to Nancy in 1872 with some of its professor. These professors are
      generally well known, but it is not the same for students who came from annexed
      departments to Nancy for studying pharmacy between 1872 and 1914. The archives
      stored in Nancy show that, during these fourty years, the quarter of pharmacy
      students in Nancy were native of Alsace or Moselle. We specify their number for
      each year after annexation. Some situations, illustrated by examples, are
      possible: young men who came in France before annexation, students who came with
      their family when they were children, pharmacists with a diploma obtained in
      Strasbourg having the wish to emigrate in France some years later. Our results
      lead to questions whose answers are difficult to formulate and would perhaps
      justify another study: what were the reasons for the obtaining of the french
      pharmacist diploma ?, what was the professional activity of these pharmacists ?,
      what was their posture during the First World War, did some of them return to
      Alsace or Moselle after the war? Whatever the answers, the presence of these <<
      Alsaciens-Lorrains >> students was significant and precious for the school of
      pharmacy of Nancy at this period.

PMID- 15264371
TI  - [7th Nationwide Conference on DNA diagnosis, cellular and gene therapy. Prague,
      11-12 December 2003. Abstracts].

PMID- 15264372
TI  - [Re the article by J. Holcik: Health and money].

PMID- 15264373
TI  - Polish survivors tell their stories.

PMID- 15264374
TI  - Immunosenescence: what is it and what can be done about it? Session 20 of the BSI
      Annual Congress, Harrogate, December, 2003.

PMID- 15264375
TI  - Fishing for Foucault.

PMID- 15264376
TI  - Wait times: the appropriateness of the methodology and how they affect patients.

PMID- 15264377
TI  - Ethical dilemmas encountered while operating and teaching in a developing
      country.

PMID- 15264378
TI  - Monitoring trends in waiting periods in Canada for elective surgery: validation
      of a method using administrative data.
AB  - BACKGROUND: Provincial governments require timely, economical methods to monitor
      surgical waiting periods. Although use of prospective procedure-specific
      registers would be the ideal method, a less elaborate system has been proposed
      that is based on physician billing data. This study assessed the validity of
      using the date of the last service billed prior to surgery as a proxy for the
      beginning of the post-referral, pre-surgical waiting period. METHOD: We examined
      charts for 31,824 elective surgical encounters between 1992 and 1996 at an
      Ontario teaching hospital. The date of the last service before surgery (the last
      billing date) was compared with the date of the consultant's letter indicating a
      decision to book surgery (i.e., to begin waiting). RESULTS: Several surgical
      specialties (but excluding cardiac, orthopedic and gynecologic) had a close
      correlation between the dates of the last pre-surgery visit and those of the
      actual decision to place the patient on the waiting list. Similar results were
      found for 12 of 15 individually studied procedures, including some orthopedic and
      gynecological procedures. CONCLUSION: Used judiciously, billing data is a timely,
      inexpensive and generally accurate method by which provincial governments could
      monitor trends in waiting times for appropriately selected surgical procedures.

PMID- 15264379
TI  - Waiting for an operation: parents' perspectives.
AB  - OBJECTIVE: To determine parents' attitudes toward and acceptance of waiting times
      for their child's operation. DESIGN: Waiting times were measured by a cross
      sectional method. A descriptive survey was conducted of families with a child
      waiting for a non-urgent operation. SETTING: A university teaching hospital.
      SUBJECTS: Parents of children (age < 20 yr) waiting for non-urgent pediatric
      general-surgery operations. MAIN OUTCOME MEASURES: Parents' concerns and
      attitudes about waiting for their child's operation, how it was affecting the
      child and family, how urgent they felt the need for surgery was, and what they
      thought was a reasonable maximum waiting period. RESULTS: Of 89 patients waiting
      for non-urgent pediatric general-surgery operations at the time of the survey,
      61% had been waiting > 6 months and 30% > 12 months. Of the 57 families (64%) who
      returned completed surveys, 94% reported the wait to be emotionally stressful for
      the family; 81.5% expected their child's quality of life would improve after the
      operation. As for length of wait, 83% felt that > 3 months was unacceptable, and
      98% > 6 months. CONCLUSIONS: Parents of children waiting for pediatric general
      surgery operations thought that the need for the operation was significantly more
      urgent then their classification of elective. They felt that waiting periods
      should not exceed 3 months. Long waiting periods are stressful for both family
      and child. Parental perceptions are important when considering strategies for
      wait-list management.

PMID- 15264380
TI  - Implementation of a successful endovascular surgical program in a non-teaching
      tertiary-care centre in Ontario.
AB  - Endovascular surgical techniques have become an accepted standard of care for
      high-risk patients with abdominal aortic aneurysms and for certain patients with
      thoracic aortic pathology and peripheral arterial aneurysms. In Canada,
      endovascular surgery has been concentrated in tertiary-care academic teaching
      institutions. As the technology evolves and as expertise advances, the
      applicability of endovascular techniques will expand. With time, and as the
      demand for endovascular techniques rises, this expertise will increasingly need
      to be delivered by dedicated vascular surgical services in nonteaching
      institutions. The dissemination of endovascular surgical capabilities represent a
      unique challenge. We report the successful implementation of an endovascular
      surgical program in a tertiary-care nonteaching institution using a carefully
      planned preceptorship model. We review our initial 49 cases and discuss 6 factors
      important to the successful establishment of an endovascular surgical service:
      education, teamwork, strict selection of patients, use of a single stent-graft
      manufacturer, industry support and endovascular preceptorship. Our experience may
      be used as a model by other institutions in Canada.

PMID- 15264381
TI  - Survey of colorectal cancer screening practices in a large Canadian urban centre.
AB  - INTRODUCTION: Colorectal carcinoma (CRC) is an ideal tumour for population-based
      screening policies. Screening guidelines are based on differing levels of
      evidence and opinion. The objective of this study was to determine current CRC
      screening practices in Alberta. METHODS: A questionnaire was mailed to all family
      physicians, gastroenterologists, general and colorectal surgeons, and general
      internal medicine specialists in a large Canadian urban centre. Results tabulated
      included response rate, specialty, presence/absence of a screening policy, and
      policy type. RESULTS: The 922 surveys mailed resulted in a 61% response rate.
      Among the responses, 58% (95% confidence interval [CI] 53.6%-62.6%) of physicians
      recommended screening to healthy individuals without a family history of CRC, and
      96% (CI 94.7%-98%; p < 0.0001) to those with a family history. For patients
      without a family history of CRC, the majority of physicians chose the age of 50
      to initiate screening (63%) by fecal occult blood testing (79%) or, less
      frequently, colonoscopy (26%). Screening frequency varied by the modality used.
      In individuals with a family history of CRC, most physicians initiated screening
      prior to the index case (45%) or by age 40 (31%), mostly with colonoscopy (84%);
      screening frequency varied mainly by modality. CONCLUSION: Despite the evidence
      supporting CRC screening in all persons at average risk, only 58% of physicians
      currently recommend screening to patients with no family history of CRC. Fecal
      occult blood testing was recommended most frequently in this subgroup, whereas
      most physicians screen people with a family history of CRC via colonoscopy,
      suggesting that they believe it to be a superior screening modality. As this
      looks to be the trend in practice, a randomized controlled trial comparing fecal
      occult testing with screening colonoscopy is needed.

PMID- 15264383
TI  - Radiology for the surgeon: musculoskeletal case 32. Divot fracture of the tibia.

PMID- 15264382
TI  - Surgical images: soft tissue. Right paraduodenal hernia.

PMID- 15264384
TI  - Surgical Education and Self-assessment Program (SESAP). Malocclusion.

PMID- 15264385
TI  - Users' guide to the surgical literature. How to assess a randomized controlled
      trial in surgery.

PMID- 15264386
TI  - Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 10.
      Laparoscopy-assisted colectomy versus open colectomy for treatment of non
      metastatic colon cancer: a randomized trial.

PMID- 15264387
TI  - The management of dysplasia associated with ulcerative colitis: colectomy versus
      continued surveillance.

PMID- 15264388
TI  - Artery transposition and carotid endarterectomy done simultaneously with stent
      graft repair of an aneurysm of the aortic isthmus.

PMID- 15264389
TI  - Residual appendix producing small-bowel obstruction after laparoscopic
      appendectomy.

PMID- 15264390
TI  - Total hip arthroplasty in a patient with neurofibromatosis type I and recurrent
      spontaneous hip dislocation.

PMID- 15264391
TI  - Spontaneous splenic rupture in infectious mononucleosis treated by embolization
      of the splenic artery.

PMID- 15264392
TI  - Late complication of extended cervical mediastinoscopy.

PMID- 15264393
TI  - Acute renal failure in the critically ill: impact on morbidity and mortality.

PMID- 15264394
TI  - Acute renal failure in the intensive care unit. Risk factors.

PMID- 15264395
TI  - Pathophysiology of ischemic acute renal failure. Inflammation, lung-kidney cross
      talk, and biomarkers.

PMID- 15264396
TI  - Pathophysiology of sepsis and multiple organ failure: pro- versus anti
      inflammatory aspects.

PMID- 15264397
TI  - Tropical acute renal failure.

PMID- 15264398
TI  - Mechanisms underlying combined acute renal failure and acute lung injury in the
      intensive care unit.

PMID- 15264399
TI  - Cytokine single nucleotide polymorphism. Role in acute renal failure.
AB  - Although the pathogenesis of ARF is heterogeneous and results from a combination
      of different environmental influences and host responses, there is overwhelming
      data to suggest a common pathway that involves pro- and anti-inflammatory
      molecules, which in turn, determines the extent of tissue injury. The number of
      recognized cytokine gene polymorphisms is growing daily. The development of
      cytokine gene mapping may help identify patients in whom an excessive systemic
      inflammatory response may follow a therapeutic intervention (e.g. CABG, contrast
      administration), and who may be at increased risk for developing acute organ
      dysfunction. Through these advances, tools may be developed to better understand,
      prevent and treat ARF. Genetic epidemiology studies may help characterize the
      importance of genetic markers in the development of ARF. This would require large
      prospective cohort studies aimed at examining associations between genetic
      markers, urinary (urine KIM-1 and NAG) and circulating (serum creatinine) markers
      of kidney injury. Once firmly established, the association of a particular
      genetic profile and outcome could be used to risk stratify patients for the
      development of ARF (fig. 4). Ultimately, cytokine-modulating therapies could be
      employed on the basis of genotypic risk stratification with the goal to prevent
      kidney injury or minimize its deleterious effects on patient outcome.

PMID- 15264400
TI  - Mechanisms of immunodysregulation in sepsis.

PMID- 15264401
TI  - Goals of resuscitation from circulatory shock.

PMID- 15264402
TI  - Intravenous fluids and acid-base balance.

PMID- 15264403
TI  - Glucose control in the critically ill.

PMID- 15264404
TI  - Dysnatremias in the critical care setting.

PMID- 15264405
TI  - Rasburicase therapy in acute hyperuricemic renal dysfunction.

PMID- 15264406
TI  - Diuretics in acute renal failure?

PMID- 15264407
TI  - How to manage vasopressors in acute renal failure and septic shock.

PMID- 15264408
TI  - Management of vascular catheters for acute renal replacement therapy.

PMID- 15264409
TI  - Relationship between blood flow, access catheter and circuit failure during CRRT:
      a practical review.

PMID- 15264410
TI  - CRRT: selection of patients and starting criteria.

PMID- 15264411
TI  - Fluid composition for CRRT.

PMID- 15264412
TI  - Anticoagulation for continuous renal replacement therapy.

PMID- 15264413
TI  - Peritoneal dialysis in acute renal failure of adults: the under-utilized
      modality.

PMID- 15264414
TI  - Intermittent hemodialysis for acute renal failure patients--an update.

PMID- 15264415
TI  - Continuous renal replacement techniques.

PMID- 15264416
TI  - Hybrid renal replacement therapies for critically ill patients.

PMID- 15264417
TI  - Pediatric acute renal failure: demographics and treatment.

PMID- 15264418
TI  - Vascular access for extracorporeal renal replacement therapy in the intensive
      care unit.

PMID- 15264419
TI  - Anticoagulation in continuous renal replacement therapy.

PMID- 15264420
TI  - Replacement and dialysate fluids for patients with acute renal failure treated by
      continuous veno-venous haemofiltration and/or haemodiafiltration.

PMID- 15264421
TI  - A practical tool for determining the adequacy of renal replacement therapy in
      acute renal failure patients.

PMID- 15264422
TI  - How to approach sepsis today?

PMID- 15264423
TI  - High volume hemofiltration in critically ill patients: why, when and how?

PMID- 15264424
TI  - Coupled plasma filtration adsorption: rationale, technical development and early
      clinical experience.

PMID- 15264425
TI  - Plasmapheresis in sepsis.

PMID- 15264426
TI  - MALDI: more than peptide mass fingerprints.
AB  - Over the past decade, matrix-assisted laser desorption/ionization (MALDI) has
      developed from a phenomenon that was interesting only to physicists and mass
      spectrometrists, and has evolved into a widespread applied ionization technique
      in chemistry, biology and biomedicine. The introduction of MALDI offers all the
      advantages of mass spectrometry (MS) for the analysis of large biomolecules.
      Proteins, carbohydrates and oligonucleotides have been analyzed with MS-inherent
      accuracy, sensitivity, resolution and speed. In addition to electrospray
      ionization-MS, MALDI-MS has a great impact on the challenges of the post-genome
      area. The recent status of MALDI application in proteomics, biomolecular
      interaction analysis-MS and carbohydrate analysis, in addition to single
      nucleotide polymorphism genotyping is reviewed.

PMID- 15264427
TI  - Stable isotope-mass spectrometric measurements of molecular fluxes in vivo:
      emerging applications in drug development.
AB  - Therapeutics require not only targets and chemical entities, but tools for
      measuring actions in vivo. Technologies for evaluating activities, filtering
      leads and predicting clinical response have lagged behind molecular discovery.
      'Systems biology' has not provided systematic methods for predicting metabolic
      effects in complex systems. The flow of molecules through complex pathways, in
      contrast, reflects the connectivity relationships and emergent control features
      of fully assembled networks, but is a quantifiable therapeutic target. This
      strategy, which combines molecular specificity with intrinsic functional
      significance, requires different tools. Here, advances in critical pathway flux
      measurement utilizing stable isotopes and mass spectrometry are described. These
      include mass isotopomer analysis, heavy-water labeling techniques, secreted
      probes of intracellular processes, and analytic advances. Several fundamental
      advantages of kinetic measurements are demonstrated. Measurement of molecular
      fluxes represents a powerful addition to drug development technology.

PMID- 15264428
TI  - Metabonomics: systems biology in pharmaceutical research and development.
AB  - Metabonomics uses a combination of data-rich analytical chemical methods such as
      nuclear magnetic resonance spectroscopy and mass spectrometry together with
      chemometrics for profiling metabolism and interpreting metabolic fingerprints in
      complex biological systems. The methods have been applied in many areas of
      relevance to pharmaceutical research and development, including drug safety
      assessment, characterization of genetically modified animal models of disease,
      diagnosis of human disease, understanding physiological variation and drug
      therapy monitoring. As well as providing a novel means of sample classification
      and effect evaluation, the approach can lead to identification of combinations of
      biomarkers for those effects. These attributes mean that metabonomics will be
      integral in the drive towards personalized healthcare.

PMID- 15264429
TI  - Circulating nucleic acids in plasma and serum: past, present and future.
AB  - Circulating nucleic acids have been detected in plasma/serum from cancer patients
      with a variety of tumor types. Polymerase chain reaction techniques provide a
      ubiquitous and facile approach for the identification of these tumor-associated
      genetic alterations from a minimal amount of tissue and body fluids. Increased
      levels of free DNA and RNA during malignancy, as well as in various medical
      conditions and infectious states, offers potential clinical utility for disease
      screening, diagnosis, prognosis, assessing occult disease progression,
      identifying potential therapeutic targets and monitoring treatment response.
      Additionally, elevated fetal DNA and RNA circulate in maternal blood and may
      serve as a diagnostic aide for assessing chromosomal abnormalities, fetal sexing
      and monitoring complications associated with pregnancy. Issues persist regarding
      the characteristics, etiology and potential pathological consequences of
      circulating cell-free DNA and RNA. Regardless, disease surveillance using nucleic
      acid-based assays for the evaluation of plasma/serum and body fluids provides a
      non-invasive and highly practical method for assessing patients.

PMID- 15264430
TI  - Photochemical drug and gene delivery.
AB  - The utilization of macromolecules in the therapy of cancer and other diseases is
      becoming increasingly relevant. Recent advances in molecular biology and
      biotechnology have made it possible to improve the targeting and design of
      cytotoxic agents or DNA complexes for clinical applications. In many cases, to
      achieve the desired biological effect of these macromolecules, internalization to
      the cell cytosol is crucial. Although new delivery systems have improved the
      cellular uptake of macromolecules, tissue penetration, cellular uptake and
      efficient transfer of the molecules into the cytosol of target cells are still
      fundamental obstacles. At an intracellular level, the greatest obstruction for
      cytosolic release of the therapeutic molecule is the membrane barrier of
      endocytic vesicles. Photochemical activation and delivery of drugs and genes are
      novel technologies to overcome these obstacles. The background theory to these
      technologies is described in this review and recent data in this field are
      discussed.

PMID- 15264431
TI  - Gene expression profiling of anticancer immune responses.
AB  - Anticancer immune responses can be enhanced by immune manipulation, however, the
      biological mechanism responsible for these immune responses remains largely
      unexplained. Conventional immunology researchers have extensively studied
      specific interactions between immune and cancer cells, and additional
      investigations have identified co-factors that may enhance the effectiveness of
      such interactions. As the molecular understanding of individual interactions
      increases, it is becoming apparent that no single mechanism can explain the
      phenomenon of tumor rejection. The contribution of several components of the
      innate and adaptive immune response is likely to be required for successful tumor
      rejection. These components may be variably recruited and activated by molecules
      with immune modulatory properties being produced by tumor and bystander cells
      within the tumor micro-environment. Such complexity can only be appreciated and
      solved by high-throughput tools capable of providing a global view of biological
      processes as they occur. This review will present selected examples of how high
      throughput gene expression profiling may contribute to the understanding of
      anticancer immune responses. As reviews on technological aspects of the genomic
      analysis of cancer are already available, this review will provide a speculative
      discussion about their potential usefulness.

PMID- 15264432
TI  - Pharmacogenomics in breast cancer: current trends and future directions.
AB  - Pharmacogenomics is the study of genetic variations between individuals to
      predict the risk of toxic side effects and the probability that a patient will
      respond to single- or multidrug chemotherapy. Breast cancer remains one of the
      most common cancers among women worldwide and is second only to lung cancer in
      cancer-related death. A better understanding of the mechanisms of initiation and
      progression of breast cancer is needed for early diagnosis and development of
      better therapeutic methodologies. Differences in cancer patients' responses to
      chemotherapy have often been attributed to pathogenesis and severity of the
      disease, drug interactions, patient's age, gender, nutritional status, organ
      functions and tumor biology. It is now well recognized that genetic variations in
      drug target genes, disease pathway genes and drug metabolizing enzymes can have
      greater influence on drug efficacy and toxicity. In addition, germline variants
      can be used to study breast cancer susceptibility, as well as the variable
      response to both drug and radiation therapy used in the treatment of breast
      cancer. This review discusses clinically relevant individual gene variations that
      influence breast cancer susceptibility and cancer therapy, as well as the
      microarray-based expression profiling studies that have great potential in cancer
      pharmacogenomics in terms of tumor classification, drug and biomarker discovery
      and drug efficacy testing.

PMID- 15264433
TI  - Pharmacogenomics of HIV.
AB  - The antiretroviral treatment of HIV infection has expanded tremendously in the
      last few years. This trend is mainly a result of new assays, genetic advances and
      recombinant DNA technologies providing new insights into HIV virology, pathology
      and resistance mechanisms. Since 1995, the use of highly active antiretroviral
      therapy (HAART) as a combination of substances directed against various steps in
      the viral life cycle, has led to significant decreases in the morbidity and
      mortality associated with HIV infections. The ability to quantify viral load and
      to perform sequence analyses represent valuable tools both for understanding the
      pathogenic actions of the virus and for clinical drug monitoring of HIV-infected
      patients. Laboratory tests have been developed and validated to help predict
      which antiviral substances may be more effective to control viral replication in
      a given patient. Genotypic and phenotypic assays have been developed to assess
      HIV antiviral resistance. The ability to predict drug response from a certain
      genotypic or phenotypic setting with respect to drug absorption, drug metabolism
      and drug elimination is continually evolving. This may lead to significant
      changes in drug plasma concentrations and may affect the efficacy and toxicity of
      antivirals. More recently, drug/drug interactions and mutation/drug correlations
      have been discovered. However, the optimal usage of pharmacogenetic and
      pharmacogenomic tools in the clinic still remains to be defined. This review
      summarizes mechanisms of drug bioavailability with respect to pharmacogenomics
      and discusses the impact and clinical benefit of 'personalized' HIV therapy.

PMID- 15264434
TI  - The role of phenotyping and replication capacity in anti-HIV therapeutics.
AB  - The management of antiretroviral-experienced and -naive HIV-infected patients is
      becoming increasingly complex with the emergence of multidrug-resistant viruses
      and with the inter-relationships between numerous virological, immunological and
      therapeutic factors. In addition to standard surrogate markers of peripheral CD4+
      T-cell counts and plasma viral loads, viral resistance phenotype, replication
      capacity and genotype assays serve as objective measures of viral properties,
      which presumably reflect, to a certain degree, what is occurring in vivo. This
      review explores the principles behind, and the basic science and clinical
      evidence supporting the application of viral resistance phenotypic assays and
      replication capacity assays in the therapeutic management of HIV disease.

PMID- 15264435
TI  - Technology evaluation: abatacept, Bristol-Myers Squibb.
AB  - Bristol-Myers Squibb is developing the fusion protein abatacept for the potential
      treatment of various immunological disorders, including rheumatoid arthritis,
      multiple sclerosis and systemic lupus erythematosus. Abatacept is undergoing
      phase III clinical trials.

PMID- 15264436
TI  - Technology evaluation: ISIS-113715, Isis.
AB  - Isis is developing ISIS-113715, an antisense inhibitor of the PTP1B gene, for the
      potential treatment of type 2 diabetes and obesity. ISIS-113715 is undergoing
      phase II clinical trials.

PMID- 15264437
TI  - Technology evaluation: pertuzumab, Roche/Genentech/Chugai.
AB  - Genentech, Roche and Chugai are developing pertuzumab, a next-generation
      trastuzumab-like molecule (an anti-HER/neu monoclonal antibody), for the
      potential treatment of cancer. Pertuzumab is currently undergoing phase II
      clinical trials.

PMID- 15264438
TI  - Technology evaluation: rh lactoferrin, Agennix.
AB  - Agennix is developing recombinant human (rh) lactoferrin, a glycoprotein with
      antibiotic, anti-inflammatory and immunomodulatory activity, for the potential
      treatment of cancers, asthma and chronic wounds. rh Lactoferrin is currently
      undergoing phase II clinical trials.

PMID- 15264439
TI  - A meta-analysis of the published research on the affective, cognitive, and
      behavioral effects of corporal punishment.
AB  - The present study is a meta-analysis of the published research on the effects of
      corporal punishment on affective, cognitive, and behavioral outcomes. The authors
      included 70 studies published between 1961 and 2000 and involving 47,751 people.
      Most of the studies were published between 1990 and 2000 (i.e., 53 or 68%) and
      were conducted in the United States (65 or 83.3%). Each of the dependent
      variables was coded, and effect sizes (ds) were computed. Average unweighted and
      weighted ds for each of the outcome variables were .35 and .20 for affective
      outcomes, .33 and .06 for cognitive outcomes, and .25 and .21 for behavioral
      outcomes, respectively. The analyses suggested small negative behavioral and
      emotional effects of corporal punishment and almost no effect of such punishment
      on cognition. Analyses of several potentially moderating variables, such as
      gender or socioeconomic status, and the frequency or age of first experience of
      corporal punishment, the relationship of the person administering the discipline,
      and the technique of the discipline all had no affect on effect size outcome.
      There was insufficient data about a number of the moderator variables to conduct
      meaningful analyses. The results of the present meta-analysis suggest that
      exposure to corporal punishment does not substantially increase the risk to youth
      of developing affective, cognitive, or behavioral pathologies.

PMID- 15264440
TI  - From empire to democracy: effects of social progress on Turkish writers.
AB  - What is the effect of a society's culture on the creative writers living there?
      Few cultures have had such a event as Ataturk's 1920 revolution that changed
      Turkey from a monarchy ruled by sultans into a republic. How would such a
      dramatic shift in a country's history be reflected in the accomplishments and
      characteristics of its writers? In this study, the authors investigated 948
      eminent Turkish writers. Variables of gender, era, type of writing, education
      level, profession, and winning an award were all analyzed. The type of writing
      (fiction, poetry, plays, or nonfiction) and the era in which the writing was
      produced were both predictive of whether an author won a literary award. Before
      1920, fiction writers received more awards than poets; after 1920, poets received
      more awards. In addition, professional writers were more likely to win awards
      than were professional politicians. Reasons for these findings are discussed with
      an emphasis on cultural and historical influences.

PMID- 15264442
TI  - Self-serving judgments about winning the lottery.
AB  - Although myths and stereotypes about lottery winners tend to be negative (e.g.,
      winners become extravagant), people continue to spend billions of dollars buying
      lottery tickets in the hope of winning. The authors applied findings from the
      self-enhancement literature to understand this paradox. Eighty college students
      received class credit for their participation, in which they read a scenario that
      asked them to imagine that they, or a target other, had won a lottery.
      Participants' responses to a 34-item questionnaire displayed a self-serving bias,
      such that changes to the self were expected to be more positive than changes to
      the other. For several items, this effect was moderated by the participant's
      gender. The present research indicates that the pervasive tendency to display
      self-serving biases can apply to future-oriented processing, an under-researched
      topic.

PMID- 15264441
TI  - Thinking styles: university students' preferred teaching styles and their
      conceptions of effective teachers.
AB  - In the present study, the author investigated the role of thinking styles in
      university students' preferences for teaching styles and their conceptions of
      effective teachers. Students (121 men and 134 women) from the University of Hong
      Kong responded to 3 self-report tests: the Thinking Styles Inventory-Revised (R.
      J. Sternberg, R. K. Wagner, & L-F. Zhang, 2003), the Preferred Thinking Styles in
      Teaching Inventory (L-F. Zhang, 2003c), and the Effective Teacher Inventory (L-F.
      Zhang, 2003b). Results indicated that even after age, gender, and academic
      discipline were controlled, particular thinking styles predisposed students to
      particular teaching styles. Moreover, as expected, students were open to more
      than just teaching styles that precisely matched their own thinking styles.
      Results also indicated that students' thinking styles made a difference in their
      conceptions of effective teachers. Discussions are focused on the study's
      contributions to both the style literature and the growing body of knowledge on
      characteristics of effective teachers.

PMID- 15264443
TI  - Self-estimates of intelligence: a study in two African countries.
AB  - Black and White South Africans (n = 181) and Nigerians (n = 135) completed a
      questionnaire concerning the estimations of their own and their relatives'
      (father, mother, sister, brother) multiple intelligences as well as beliefs about
      the IQ concept. In contrast to previous results (A. Furnham, 2001), there were
      few gender differences in self-estimates. In a comparison of Black and White
      South Africans, it was clear the Whites gave higher estimates for self, parents,
      and brothers. However, overall IQ estimates for self and all relatives hovered
      around the mean of 100. When Black South Africans and Nigerians were compared,
      there were both gender and nationality differences on the self-estimates with men
      giving higher self-estimates than women and Nigerians higher self-estimates than
      South Africans. There were also gender and nationality differences in the answers
      to questions about IQ. The authors discuss possible reasons for the relatively
      few gender differences in this study compared with other studies as well as
      possible reasons for the cross-cultural difference.

PMID- 15264444
TI  - Celebrity and religious worship: a refinement.

PMID- 15264445
TI  - Predictive validity of the SVR-20 and Static-99 in a Dutch sample of treated sex
      offenders.
AB  - In this retrospective study, the interrater reliability and predictive validity
      of 2 risk assessment instruments for sexual violence are presented. The SVR-20,
      an instrument for structured professional judgment, and the Static-99, an
      actuarial risk assessment instrument, were coded from file information of 122 sex
      offenders who were admitted to a Dutch forensic psychiatric hospital between 1974
      and 1996 (average follow-up period 140 months). Recidivism data (reconvictions)
      from the Ministry of Justice were related to the risk assessments. The base rate
      for sexual recidivism was 39%, for nonsexual violent offenses 46%, and for
      general offenses 74%. Predictive validity of the SVR-20 was good (total score: r
      = .50, AUC = .80; final risk judgment: r = .60, AUC = .83), of the Static-99
      moderate (total score: r = .38, AUC =.71; risk category: r = .30, AUC = .66). The
      SVR-20 final risk judgment was a significantly better predictor of sexual
      recidivism than the Static-99 risk category.

PMID- 15264446
TI  - Identifying three types of violent offenders and predicting violent recidivism
      while on probation: a classification tree analysis.
AB  - This study employs classification tree analysis (CTA) to address whether 3 groups
      of violent offenders have similar or different risk factors for violent
      recidivism while on probation. A sample of 1344 violent offenders on probation
      was classified as generalized aggressors (N = 302), family only aggressors (N =
      321), or nonfamily only aggressors (N = 717). The strongest predictor of violent
      recidivism while on probation was whether the offender was a generalized
      aggressor or not, with generalized aggressors more likely to be arrested for new
      violent crimes. Prior arrests for violent crimes predicted violent recidivism of
      generalized aggressors, but did not significantly predict violent recidivism of
      family only and nonfamily only aggressors. For generalized aggressors and family
      only batterers, treatment noncompliance was an important risk predictor of
      violent recidivism. CTA compared to logistic regression classified a higher
      percentage of cases into low-risk and high-risk groups, provided higher
      improvement in classification accuracy of violent recidivists beyond chance
      performance, and provided a better balance of false positives and false
      negatives. The implications for the risk assessment and domestic violence
      literature are discussed.

PMID- 15264447
TI  - The effect of intellectual disability on children's recall of an event across
      different question types.
AB  - This research examined the performance of 80 children aged 9-12 years with either
      a mild and moderate intellectual disability when recalling an innocuous event
      that was staged in their school. The children actively participated in a 30-min
      magic show, which included 21 specific target items. The first interview (held 3
      days after the magic show) provided false and true biasing information about
      these 21 items. The second interview (held the following day) was designed to
      elicit the children's recall of the target details using the least number of
      specific prompts possible. The children's performance was compared with that of 2
      control groups; a group of mainstream children matched for mental age and a group
      of mainstream children matched for chronological age. Overall, this study showed
      that children with either a mild or moderate intellectual disability can provide
      accurate and highly specific event-related information. However, their recall is
      less complete and less clear in response to free-narrative prompts and less
      accurate in response to specific questions when compared to both the mainstream
      age-matched groups. The implications of the findings for legal professionals and
      researchers are discussed.

PMID- 15264448
TI  - Evaluating stranger and acquaintance rape: the role of benevolent sexism in
      perpetrator blame and recommended sentence length.
AB  - In most jurisdictions, the law does not recognize the distinction between
      stranger and acquaintance rape. However, these two types of rape seem to elicit
      different responses from both lay observers and legal practitioners. Two studies
      investigating the role of benevolent sexism (BS) in accounting for participants'
      responses to acquaintance vs. stranger rape perpetrators are reported.
      Participants were presented with vignettes describing either an acquaintance rape
      or a stranger rape. As predicted, relative to low-BS individuals, participants
      who scored high in BS attributed less blame (Study 1) and recommended shorter
      sentences (Study 2) for the acquaintance rape perpetrator. Benevolent sexism was
      unrelated to reactions to the perpetrator in the stranger rape condition.

PMID- 15264449
TI  - How the need for cognition scale predicts behavior in mock jury deliberations.
AB  - The role of Need for Cognition (NC) in mock jury deliberations was examined.
      Study 1 showed that when groups of 4 (2 high and 2 low in NC) deliberated
      together, high-NCs spoke significantly longer than low-NCs and were perceived as
      more active and more persuasive. High-NCs were not, however, viewed as generating
      arguments that were more valid or more logical. In Study 2, participants
      deliberated in dyads with a confederate who delivered either strong or weak
      arguments against the participant's position. Contrary to expectation, low-NCs
      were more responsive to differences in argument quality. The findings suggest
      that, in mock jury deliberations, high-NCs are the active participators whereas
      low-NCs are the quiet contemplators. Implications for legal practice and policy
      are discussed.

PMID- 15264450
TI  - Lineup identification by children: effects of clothing bias.
AB  - This study examined effects of clothing cues on children's identification
      accuracy from lineups. Four- to 14-year-olds (n = 228) saw 12 video clips of
      individuals, each wearing a distinctly colored shirt. After watching each clip
      children were presented with a target-present or target-absent photo lineup.
      Three clothing conditions were included. In 2 conditions all lineup members wore
      the same colored shirt; in the third, biased condition, the shirt color of only
      one individual matched that seen in the preceding clip (the target in target
      present trials and the replacement in target-absent trials). Correct
      identifications of the target in target-present trials were most frequent in the
      biased condition, whereas in target-absent trials the biased condition led to
      more false identifications of the target replacement. Older children were more
      accurate than younger children, both in choosing the target from target-present
      lineups and rejecting target-absent lineups. These findings suggest that a simple
      clothing cue such as shirt color can have a significant impact on children's
      lineup identification accuracy.

PMID- 15264451
TI  - Transplant pharmacists: key to a successful transplant program.

PMID- 15264453
TI  - Hepatotoxicity of herbal remedies: an emerging dilemma.
AB  - The surge in consumption of herbal remedies has been stimulated by several
      factors, including the notion that all herbal products are safe and effective,
      consumers becoming more proactive in self-treating, and lack of regulation by the
      Food and Drug Administration. Although herbal remedies are generally perceived as
      harmless, reports of hepatotoxicity associated with herbal use are accumulating,
      suggesting they are not completely innocuous. On the basis of various case
      reports, the liver injury from herbal remedies has ranged from mild elevations of
      liver enzymes to fulminant liver failure requiring liver transplantation.
      Although regulation by the Food and Drug Administration may be part of the
      solution, increasing public awareness and educating healthcare professionals
      about the potential dangers of herbal preparations will need to be implemented.
      This article reviews the hepatotoxicity of herbal remedies as reported in the
      literature and discusses issues related to regulation of herbal preparations.

PMID- 15264452
TI  - Chronic allograft nephropathy: pathogenesis and management of an important
      posttransplant complication.
AB  - Chronic allograft nephropathy is a devastating complication of kidney
      transplantation that is responsible for a significant proportion of graft loss.
      This complication is characterized by a progressive decline in kidney function,
      which is not attributable to a specific cause. Many risk factors exist for the
      development of chronic allograft nephropathy, including donor-, recipient-, and
      transplant-related factors (eg, use of calcineurin inhibitors and acute rejection
      episodes), as well as comorbid conditions such as hypertension and
      hyperlipidemia. There is no definitive treatment for this complication;
      management has focused on minimization or withdrawal of calcineurin inhibitors in
      conjunction with addition of sirolimus or mycophenolate mofetil. Alterations in
      the immunosuppressive regimen must be done cautiously, as precipitating acute
      rejection will cause further damage to the allograft. Optimal control of blood
      pressure, particularly with the use of agents such as angiotensin II receptor
      blockers, in conjunction with management of dyslipidemia may be effective
      concurrent therapies in patients with chronic allograft nephropathy.

PMID- 15264454
TI  - Use of antidepressant drugs in transplant recipients.
AB  - Depression is the most prevalent psychiatric disorder in transplant recipients
      and may lead to noncompliance and negative outcomes without psychosocial and
      pharmacologic interventions. The pharmacologic treatment of depression in this
      patient population is complicated by complex immunosuppressant drug regimens and
      multiple potential drug interactions that can adversely affect the newly
      transplanted organs. This review provides a brief overview of the currently
      available antidepressant medications and highlights the clinically important
      features each class of agents in transplant recipients. Newer agents selective
      serotonin reuptake inhibitors, venlafaxine, bupropion, nefazodone, and
      mirtazapine are discussed as well as tricyclic antidepressants and monoamine
      oxidase inhibitors. A brief discussion of St. John's wort and its impact on
      posttransplant drug therapy is also included.

PMID- 15264455
TI  - Critical care pharmacy in donor management.
AB  - Significant systemic changes occur following neurologic insult and subsequent
      brain death. If left untreated, the hemodynamic instability and neuroendocrine
      alterations that ensue may significantly affect the quality of the donor organs,
      and contribute to posttransplant allograft dysfunction. A number of pharmacologic
      interventions are often implemented in an attempt to stabilize donor hemodynamics
      and optimize organ perfusion, thereby increasing the number and quality of
      cadaveric donor organs available for transplantation. This review provides a
      summary of these interventions, with an emphasis placed on hormonal
      resuscitation, which involves utilizing such agents as thyroxin, vasopressin,
      insulin, and corticosteroids.

PMID- 15264456
TI  - Management of opportunistic infections in solid-organ transplantation.
AB  - Solid-organ transplantation is often the last alternative in many patients with
      end-stage organ disease. Although advances in immunosuppressive regimens,
      surgical techniques, organ preservation, and overall management of transplant
      recipients have improved graft and patient survival, infectious complications
      remain problematic. Bacterial, fungal, viral, and parasitic infections are
      implicated after transplantation depending on numerous factors, such as degree of
      immunosuppression, type of organ transplant, host factors, and period after
      transplantation. Proper prophylactic and treatment strategies are imperative in
      the face of chronic immunosuppression, nosocomial and community pathogens,
      emerging drug resistance, drug-drug interactions, and medication toxicities. This
      review summarizes the pathophysiology, incidence, prevention, and treatment
      strategies of common posttransplant infections.

PMID- 15264457
TI  - Polyomavirus nephropathy in kidney transplantation.
AB  - Polyomavirus nephropathy has become an important complication in kidney
      transplantation, with a prevalence of 1% to 8%. Unfortunately, the risk factors
      for polyomavirus nephropathy and renal allograft loss are not well defined. The
      definitive diagnosis is made through assessment of a kidney transplant biopsy.
      Recently, noninvasive urine and serum markers have been used to assist in
      polyomavirus nephropathy diagnosis and monitoring. Primary treatment is
      immunosuppression reduction, but must be balanced with the risks of rejection. No
      antiviral treatments for polyomavirus nephropathy have been approved by the Food
      and Drug Administration. Although cidofovir has shown in vitro activity against
      murine polyomaviruses, and has been effective in some patients, it is associated
      with significant nephrotoxicity. Graft loss due to polyomavirus nephropathy
      should not be a contraindication to retransplantation; however, experience is
      limited. This review presents potential risk factors, screening, diagnostic and
      monitoring methods, therapeutic management, and retransplantation experience for
      polyomavirus nephropathy.

PMID- 15264458
TI  - Treating gout in kidney transplant recipients.
AB  - OBJECTIVE: To review the etiology, treatment, and preventive strategies of
      hyperuricemia and gout in kidney transplant recipients. DATA SOURCES: Primary
      literature was obtained via Medline (1966-June 2003). STUDY SELECTION AND DATA
      EXTRACTION: Studies evaluating treatment and prevention of hyperuricemia and gout
      in kidney transplantation were considered for evaluation. English-language
      studies were selected for inclusion. DATA SYNTHESIS: Approximately 14,000 kidney
      transplantations were performed in the United States in 2003, and of those
      transplant recipients, nearly 13% will experience a new onset of gout. The
      prevalence of hyperuricemia is even greater. There are several mechanisms by
      which hyperuricemia and gout develop in kidney transplant recipients. Medication
      induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms.
      Prophylactic and treatment options include allopurinol, colchicine,
      corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory
      drugs. CONCLUSION: It is generally recommended to decide whether the risks of
      prophylactic therapy and treatment outweigh the benefits. Often, the risk of
      adverse events associated with agents to treat these ailments tends to outweigh
      the benefits; therefore, treatment is usually reserved for symptomatic episodes
      of acute gout. Practitioners must also decide if changes in immunosuppressive
      regimens may be of benefit on a patient-by-patient basis.

PMID- 15264459
TI  - Future immunosuppressive agents in solid-organ transplantation.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      mycophenolate sodium, everolimus, and FTY720. STUDY SELECTION AND DATA
      EXTRACTION: Clinical trials and abstracts evaluating mycophenolate sodium,
      everolimus, and FTY720 in solid-organ transplantation were considered for
      evaluation. English-language studies and published abstracts were selected for
      inclusion. DATA SYNTHESIS: Mycophenolate sodium has recently been approved by the
      Food and Drug Adminstration for marketing in the United States; everolimus and
      FTY720 are immunosuppressive agents that may soon be available in the United
      States. These agents have proven efficacy in reducing the incidence of acute
      rejection in solid-organ transplantation. Clinical trials have shown that these
      newer agents are relatively well tolerated. The most common adverse events
      associated with these agents were gastrointestinal and hematologic effects
      (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and
      hematologic effects (everolimus): and gastrointestinal effects, headache, and
      bradycardia (FTY720). CONCLUSION: Mycophenolate sodium has been approved in some
      European countries and the United States. Everolimus has been approved in some
      European countries and a new drug application has been submitted to the Food and
      Drug Administration. FTY720 is currently in phase III clinical trials and
      submission to the Food and Drug Administration for approval is a few years away.
      The approval of these agents will furnish the transplant practitioner with even
      more options for immunosuppression.

PMID- 15264460
TI  - Strategies to prevent chronic allograft nephropathy in kidney transplantation:
      focus on calcineurin inhibitors.
AB  - Chronic allograft nephropathy is one of the leading causes of long-term graft
      failure in kidney transplant recipients. The etiology of this condition is
      multifactorial, but administration of calcineurin inhibitors is often implicated.
      With the introduction of newer immunosuppressive agents, strategies for
      calcineurin inhibitor minimization, avoidance, and withdrawal have been emerging
      in the literature. These strategies may improve long-term kidney allograft
      function, but are not without risks. Results from recent clinical trials
      evaluating the safety and efficacy of these strategies to prevent chronic
      allograft nephropathy in kidney transplant recipients are summarized and
      reviewed. Patients who had never received a calcineurin inhibitor or who had
      cyclosporine withdrawn from their regimens had better kidney function than
      patients who received or kept receiving a calcineurin inhibitor. The impact of
      the improvement in kidney function on long-term graft survival remains to be
      determined. In addition, the benefit in renal function must be weighed against
      the bone marrow toxicities and/or metabolic complications associated with these
      regimens.

PMID- 15264461
TI  - Resources for patients. Coping ABCs for caregivers.

PMID- 15264462
TI  - Industry involvement in senior design courses.

PMID- 15264463
TI  - Drug eluting stents.

PMID- 15264464
TI  - Reproductive versus therapeutic cloning: science, applications, and policies.

PMID- 15264465
TI  - Animal cloning applications in agriculture.

PMID- 15264466
TI  - Why clone horses and mules?

PMID- 15264467
TI  - Cloning pigs as organ donors for humans.

PMID- 15264468
TI  - Science, technology, and potential applications of therapeutic cloning.

PMID- 15264469
TI  - Epigenetic reprogramming in cloned embryos.

PMID- 15264470
TI  - A European perspective on animal cloning and government regulation.

PMID- 15264471
TI  - Cloning laws, policies, and attitudes worldwide.

PMID- 15264472
TI  - Improving pedal power during semireclined leg cycling.

PMID- 15264473
TI  - Intelligent diagnosis of sleep apnea syndrome.

PMID- 15264474
TI  - Free will versus suicide bombers.

PMID- 15264475
TI  - Dead on arrival.

PMID- 15264476
TI  - Exploding glass eyes.

PMID- 15264477
TI  - The emerging in-silico scientist: how text-based bioinformatics is bridging
      biology and artificial intelligence.

PMID- 15264478
TI  - Opportunities and challenges.

PMID- 15264479
TI  - What is the QSR/GMP, and why should you care?

PMID- 15264480
TI  - Launching a partnership to improve animal health and welfare.

PMID- 15264481
TI  - Lords debate the future of rural practice.

PMID- 15264482
TI  - Frequent diagnoses of nephrosis in lambs in May.

PMID- 15264483
TI  - Case-control investigation of the factors affecting the risk of horses falling
      during steeplechase racing in the UK.
AB  - A concurrent case-control study of 12 UK racecourses was made between March 1,
      2000, and August 31, 2001, to identify and quantify the factors associated with
      the risk of horses falling in steeplechase races. Cases were defined as a jumping
      effort at a steeplechase fence that resulted in a fall and controls were defined
      as a successful jumping effort over any steeplechase fence at any of the 12
      racecourses within 14 days before or after the case fall. Information on the
      horse, the jockey and the race were collected and all the fences on all the
      courses were surveyed. Conditional logistic regression was used to examine the
      relationships between the predictor variables and the risk of falling. There was
      one fall per 254 jumping efforts. The risk of a horse falling decreased the more
      times it had raced on a particular racecourse. The number of fences, the distance
      from the previous fence and the nature of the previous fence also affected the
      risk of falling. If the previous fence was a water jump the risk of falling
      increased; fences that were sited on flat or slight uphill gradients (up to
      approximately 1 in 25) were associated with a lower risk of horses falling than
      downhill fences, and higher takeoff boards were associated with a higher risk of
      falling.

PMID- 15264484
TI  - Natural infections of Crenosoma vulpis and Angiostrongylus vasorum in dogs in
      Atlantic Canada and their treatment with milbemycin oxime.
AB  - Milbemycin oxime was used to treat dogs with natural infections of the fox
      lungworm, Crenosoma vulpis and the French heartworm, Angiostrongylus vasorum.
      Crenosomosis was identified in 42 of 202 dogs with clinical signs of coughing,
      dyspnoea or exercise intolerance by a Baermann analysis of faecal samples taken
      between October 2000 and October 2001. It occurred throughout Atlantic Canada
      (New Brunswick, Newfoundland, Nova Scotia and Prince Edward Island). The clinical
      signs resolved and shedding of larvae in faeces ceased in all 32 Crenosoma
      infected dogs given a single oral dose of 0.5 mg/kg milbemycin oxime for which
      the results of faecal examinations were available. Angiostrongylosis was
      identified in 16 of the 202 dogs and was restricted to the Avalon peninsula of
      Newfoundland, where 67 dogs were tested. The clinical signs resolved and shedding
      of larvae ceased in 14 of the 16 dogs treated with four, weekly oral doses of 0.5
      mg/kg milbemycin oxime. One dog with severe clinical signs died during the course
      of treatment and one owner failed to provide a faecal sample from their dog but
      reported that the clinical signs had resolved.

PMID- 15264485
TI  - Immunoglobulin A monoclonal gammopathy in two horses with multiple myeloma.
AB  - The clinical findings in two horses with secretory multiple myeloma and secondary
      immunoglobulin A (IgA) monoclonal gammopathy were non-specific and included
      weight loss, pale mucous membranes, limb oedema and bacterial respiratory tract
      infection. Consistent laboratory abnormalities included hyperproteinaemia,
      hyperglobulinaemia, hypoalbuminaemia and hypercalcaemia. The diagnosis was based
      on the presence of IgA monoclonal gammopathy in serum and urine and bone marrow
      plasmacytosis (> 10 per cent). One horse was euthanased; it had neoplastic plasma
      cell infiltrates in its kidneys, spleen, liver, bone marrow, myocardium and
      adrenal glands. The other horse was treated for a bacterial pneumonia and was
      still alive six months after it was first examined.

PMID- 15264486
TI  - Causes of lymphadenopathy in the dog and cat.

PMID- 15264487
TI  - Lingual and pharyngeal paralysis due to acute doxycycline intoxication in veal
      calves.

PMID- 15264488
TI  - Potential role of candida species in antibiotic-associated diarrhoea in a foal.

PMID- 15264490
TI  - RCVS survey on the uptake of CPD.

PMID- 15264489
TI  - Antibiotic susceptibility of Edwardsiella hoshinae isolated from northern
      bobwhite quail (Colinus virginianus).

PMID- 15264491
TI  - Change in treatment to calving interval for Cepravin Dry Cow.

PMID- 15264492
TI  - Brucella species infection in marine mammals off the Cornish coast.

PMID- 15264493
TI  - Peer relationships and social and recreational activities among adolescents and
      adults with autism.
AB  - In this study, we investigate peer relationships and participation in social and
      recreational activities among 235 adolescents and adults with autism who live at
      home. The prevalence of having friendships, peer relationships, and participating
      in social and recreational activities were all low and comparable to previous
      research. Both individual and environmental factors were investigated as
      predictors of having peer relationships and participation in social and
      recreational activities. Having peer relationships was predicted by individual
      characteristics (younger age, and less impairment in social interaction skills),
      but not by characteristics of the environment. Greater participation in social
      and recreational activities was predicted by characteristics of the individual
      with autism (greater functional independence, less impairment in social
      interaction skills, higher levels of internalizing behaviors) and characteristics
      of the environment (greater maternal participation in social and recreational
      activities, greater number of services received, and inclusion in integrated
      settings while in school).

PMID- 15264494
TI  - Intact covert orienting to peripheral cues among children with autism.
AB  - The focus of the present study was to examine covert orienting responses to
      peripheral flash cues among children with autism in a situation where attentional
      processes were taxed by the presence of distractors in the visual field. Fourteen
      children with autism (MA = 6-7 years) were compared to their MA-matched peers
      without autism on a forced choice RT covert orienting paradigm. The task
      conditions varied with regard to the target location, the validity of the cue,
      and the presence or absence of distractors. The results showed no group
      differences as both children with autism and their MA-matched peers showed
      similar effects of cue validity and distractors. These findings are inconsistent
      with the view that orienting is generally impaired in children with autism.

PMID- 15264495
TI  - Screening and identifying children with autism spectrum disorders in the public
      school system: the development of a model process.
AB  - Heightened public awareness of autism and increased prevalence estimates of
      autism spectrum disorders (ASDs) has generated a sense of urgency within the
      public school system to identify children with these disorders for targeted
      intervention. Two multidisciplinary groups of professionals, one each from two
      separate school districts, were identified and trained to provide diagnostic and
      consultative services. This paper outlines a model process for school personnel
      to develop a basic level of training and competence in recognizing and serving
      students who have an ASD by (1) providing an overview of the legal and clinical
      issues involved in screening for children with ASD within the school system, (2)
      defining a school-based professional training process and (3) outlining a school
      based ASD screening process.

PMID- 15264496
TI  - Defining the intellectual profile of Asperger Syndrome: comparison with high
      functioning autism.
AB  - Asperger syndrome (AS) is a disorder of early childhood characterized by autistic
      social deficits, subtle communication impairment, and excessive isolated
      interests. There is no history of language delay or of mental retardation.
      Despite its increasing popularity as a distinct condition, its diagnostic
      validity remains uncertain. It is still unclear to what extent AS differs from
      autism with normal intelligence sometimes referred to as high-functioning autism
      (HFA). However, some reports have suggested that persons with AS possess a
      distinct profile on tests of intelligence characterized by a high verbal IQ and a
      low performance IQ, whereas in most cases with HFA, the pattern is reversed.
      Since few studies have directly compared AS subjects with HFA controls using
      unmodified diagnostic criteria and standardized measures of assessment, in this
      report we compared 22 AS subjects with 12 HFA controls, matched on age, sex and
      level of intelligence. As a group, subjects with AS showed a higher verbal IQ and
      higher scores on information and vocabulary subtests than those with HFA.
      However, scores of several AS and HFA subjects showed a mixed pattern.
      Implications of these findings are discussed in the context of the validity of
      Asperger Syndrome.

PMID- 15264497
TI  - A systematic review of action imitation in autistic spectrum disorder.
AB  - Imitative deficits have been associated with autistic spectrum disorder (ASD) for
      many years, most recently through more robust methodologies. A fresh, systematic
      review of the significance, characteristics, and underlying mechanism of the
      association is therefore warranted. From 121 candidates, we focused on 21 well
      controlled studies involving 281 cases of ASD. Overall, children with ASD
      performed worse on imitative tasks (Combined Logit p value < .00005). The
      emerging picture is of delayed development in imitation, implicating a deficit in
      mapping neural codings for actions between sensory and motor modalities, rather
      than in motivation or executive function. We hypothesise that ASD is
      characterised by abnormal development of these mappings. such that they are
      biased towards object-oriented tasks at the expense of those required for action
      imitation per se.

PMID- 15264498
TI  - Empathising and systemising in adults with and without Asperger Syndrome.
AB  - An experiment was devised to test the empathising-systemising (E-S) theory of
      autism. Three groups of participants took part in the study: males with Asperger
      Syndrome (AS) (n = 18), males without AS, (n = 44) and females from the general
      population (n = 45). Each participant completed two tasks: one that involved
      empathising and another that involved systemising. On the empathising task,
      females scored significantly higher than control males who in turn scored higher
      than males with AS. Conversely, females scored significantly lower than both male
      groups on the systemising task, who did not differ significantly from each other.
      These results are in line with both the E-S theory of autism and the 'extreme
      male brain' theory of autism. Alternative explanations of the results are also
      explored, including an interpretation through the idea of open and closed
      systems.

PMID- 15264499
TI  - An exploration of causes of non-literal language problems in individuals with
      Asperger Syndrome.
AB  - Individuals with Asperger Syndrome (AS), a high functioning variant of Autism,
      are often noted to possess intact language ability, yet fail to use this language
      capacity to engage in interactive communication. This difficulty using language
      in a social context has been referred to as a deficit in pragmatic language. In
      particular, difficulty understanding nonliteral language devices, such as irony
      has been observed. This paper examines the veracity of two theories that have
      attempted to explain the causes of pragmatic language difficulties in individuals
      with Asperger Syndrome; the theory of Weak Central Coherence (WCC) and Social
      Inference theory. Fourteen young adults with AS and 24 age-matched controls were
      assessed on cognitive tasks measuring WCC processes, social inference or Theory
      of Mind ability, and the ability to interpret ironic remarks. Results indicated
      that the ability to understand the belief states of others is critical to
      understanding ironic language in AS.

PMID- 15264500
TI  - The comorbidity of Pervasive Developmental Disorder and Attention Deficit
      Hyperactivity Disorder: results of a retrospective chart review.
AB  - OBJECTIVE: To determine if a sample of children meeting diagnostic criteria for a
      Pervasive Developmental Disorder (PDD) display symptoms and impairment related to
      Attention Deficit Hyperactivity Disorder (ADHD) sufficient to warrant a comorbid
      diagnosis of ADHD. Further, do children with PDD displaying such symptoms
      demonstrate more impairment in daily life activities than those children only
      having PDD? METHOD: A retrospective chart review was conducted on children (N =
      57) diagnosed with the PDD's of Autism or PDD-Not Otherwise Specified (PDD-NOS),
      or ADHD. Comparative analysis of questionnaire and neuropsychological test data
      was completed to determine the severity of ADHD-like symptoms presenting among
      children with PDD. RESULTS: From the pool of subjects having PDD with sufficient
      data (N = 27), 7 or 26% met DSM-IV criteria for the combined type of ADHD. Nine
      or 33% met diagnostic criteria for the Inattentive Type of ADHD and 11 or 41% did
      not demonstrate a significant number of ADHD symptoms to warrant a comorbid
      diagnosis of ADHD. Results indicate that a subgroup of children with PDD
      displaying significant ADHD-like symptoms may in fact have ADHD thus warranting a
      comorbid diagnosis of ADHD. Current data did not suggest children with PDD and
      the combined type of ADHD demonstrated significantly more impairment in daily
      life functioning than those children only having PDD. However, this appeared
      likely the result of small sample size. The data, however, does indicate such
      children experience more difficulties in daily situations as rated by parents and
      teachers. CONCLUSION: These findings reinforce clinical observations indicating
      that some children with PDD may also experience an independent comorbid condition
      of ADHD, suggesting that a comorbid diagnosis of ADHD with PDD be considered in
      such cases. If further findings are replicated, the current exclusionary DSM-IV
      TR criteria of making such a comorbid diagnosis should be re-considered.

PMID- 15264501
TI  - Processing capacity in children and adolescents with pervasive developmental
      disorders.
AB  - This study sought to investigate whether the abnormally small P3 amplitudes
      observed in pervasive developmental disorder (PDD) are related to differences in
      processing capacity. PDD children and adolescents and their control groups
      participated in the study. Visual probe stimuli were presented during an auditory
      task with two levels of difficulty. Event-related potentials (ERP) were measured
      from 62 electrodes during task performance. All groups showed amplitude increases
      to auditory stimuli with increasing task load. Controls showed expected smaller
      P3 amplitudes to visual probes, whereas PDD subjects did not. The results suggest
      that autistic subjects show abnormal capacity allocation. Some of these
      abnormalities may dissolve over time, while others remain into adolescence.

PMID- 15264502
TI  - External validity of childhood disintegrative disorder in comparison with
      autistic disorder.
AB  - To examine the external validity of DSM-IV childhood disintegrative disorder
      (CDD), 10 children (M = 8.2 yrs) with CDD and 152 gender- and age-matched
      children with autistic disorder (AD) were compared on 24 variables. The CDD
      children had a significantly higher rate of epilepsy, significantly less uneven
      intellectual functioning, and a tendency of greater abnormality in auditory
      responsiveness than AD children, to validate CDD externally. Their short-term
      outcome, as shown in the degree of retardation, was not worse than the AD
      children, which is in disagreement with previous studies reporting worse outcomes
      in CDD than autism. These results need to be verified by a long-term prospective
      study that compares CDD and AD patients from infancy.

PMID- 15264503
TI  - Program for child with autism.

PMID- 15264504
TI  - Management of fetal pain during invasive fetal procedures. A review.
AB  - In recent years, fetal stress and analgesia draw more and more attention.
      Evidence that fetuses show a significant endocrinological and hemodynamical
      response to invasive stimuli, and that these responses can be blocked by
      analgesia, suggests that fetuses experience a stress response, even if this does
      not signify they experience "pain". Moreover, it is becoming increasingly clear
      that experiences of pain of a fetus will be "remembered" by the developing
      nervous system, perhaps for the entire life of the individual, which can probably
      lead to abnormal behavioural patterns or altered nociception. But up to now, the
      entire mechanism of fetal stress response and the optimal analgesic drug, dose
      and route of administration is not so clear.

PMID- 15264505
TI  - Cardiac tamponade and pulmonary compression due to volvulus of oesophageal
      coloplasty.
AB  - We describe an unusual case of cardiac tamponade and pulmonary compression due to
      acute volvulus of colon interposition occuring late after oesophagectomy.
      Clinical signs were suggestive of cardiac tamponade but there was no evidence of
      pericardial effusion by transthoracic echocardiography. Thoracic-CT provided the
      diagnostic clue in revealing the extrapericardial nature (a major dilatation of
      the colonic transplant) of the tamponade. This diagnosis should be considered in
      case of acute cardiopulmonary distress occuring early or late after
      oesophagectomy.

PMID- 15264506
TI  - Recovery from neuromuscular block after an intubation dose of cisatracurium and
      rocuronium in lumbar disc surgery.
AB  - BACKGROUND AND OBJECTIVE: Residual muscle paralysis remains a concern for
      anaesthesiologists. This study investigated the recovery from neuromuscular block
      (NMB) after an intubation dose of cisatracurium (C) or rocuronium (R) in 32
      patients undergoing lumbar disc surgery. METHODS: Anaesthesia was induced with
      propofol and sufentanil, and maintained with sevoflurane in nitrous oxide/oxygen.
      Patients were randomised to receive twice the ED95 of either cisatracurium (GC)
      or rocuronium (GR) before tracheal intubation. After placement in prone position,
      neuromuscular transmission was monitored at the wrist by accelerometry. NMB was
      antagonised when the TOF ratio (TOFR) was < 0.75 at muscle closure. The time from
      muscle relaxant to muscle closure, and to TOFR of 0.25 and of 0.50 were recorded.
      Data were analysed using Student's t-tests, chi-squared tests and two-way mixed
      designed ANOVA's. The prediction probability (Pk) of the times from muscle
      relaxant to muscle closure, and to TOFR of 0.25 for the necessity to antagonize
      NMB was calculated in both groups. P < 0.05 was considered statistically
      significant. RESULTS: NMB was antagonized in 8 (GC) and 6 (GR) patients,
      respectively. The time from muscle relaxant to muscle closure was shorter in
      patients whose NMB was antagonized. The Pk of this time was significant in GC
      (0.85) but not in GR (0.69). In GR contrarily to GC, the times to a TOFR of 0.25
      and 0.50 were longer in patients whose NMB was antagonized. The Pk of the time to
      TOFR of 0.25 was significant in GR (0.95) but not in GC (0.64). CONCLUSIONS: A
      single dose of cisatracurium or rocuronium may be associated to some degree of
      NMB at the end of lumbar surgery, depending on the duration of surgery and on the
      duration of action of the muscle relaxant which is more variable for rocuronium
      than for cisatracurium.

PMID- 15264507
TI  - Disability as masquerade.

PMID- 15264508
TI  - Meditation, disability, and identity.

PMID- 15264509
TI  - Fat as disability: the case of the Jews.

PMID- 15264510
TI  - Where the Girls Are: the management of venereal disease by United States military
      forces in Vietnam.

PMID- 15264511
TI  - Bug chasing, barebacking, and the risks of care.

PMID- 15264512
TI  - "Without us all told": Paul Monette's vigilant witnessing to the AIDS crisis.

PMID- 15264513
TI  - Memento morbi: Lam Qua's paintings, Peter Parker's patients.

PMID- 15264514
TI  - Loss and the persistence of memory: "the case of George Dedlow" and disabled
      Civil War veterans.

PMID- 15264515
TI  - Extrapolating race in GATTACA: genetic passing, identity, and the science of
      race.

PMID- 15264516
TI  - Limnology of Botos Lake, a tropical crater lake in Costa Rica.
AB  - Botos Lake, located at the Poas Volcano complex (Costa Rica) was sampled eight
      times from 1994 to 1996 for physicochemical conditions of the water column and
      phytoplanktonic community composition. Depth was measured at fixed intervals in
      several transects across the lake to determine its main morphometric
      characteristics. The lake has an outlet to the north. It is located 2580 m above
      sea level and is shallow, with a mean depth of 1.8 m and a relative depth of 2.42
      (surface area 10.33 ha, estimated volume 47.3 hm3). The lake showed an isothermal
      water column in all occasions, but it heats and cools completely according to
      weather fluctuations. Water transparency reached the bottom on most occasions (>
      9 m). The results support the idea that the lake is polymictic and oligotrophic.
      The lake has at least 23 species of planktonic algae, but it was always dominated
      by dinoflagellates, especially Peridinium inconspicuum. The shore line is
      populated by a sparse population of Isoetes sp. and Eleocharis sp. mainly in the
      northern shore where the bottom has a gentle slope and the forest does not reach
      the shore.

PMID- 15264517
TI  - [The phytoplankton community of Punta Morales, Nicoya Gulf, Costa Rica ].
AB  - Three daily samplings of the phytoplankton community were made at two consecutive
      days in March, April, May, September, October, November and December 1997, at
      Punta Morales, Golfo de Nicoya, Costa Rica. Samples were collected during each
      tide at depths of 50% and 10% of light penetration using a Niskin bottle. A total
      of 43 taxa were identified. Centric diatoms, pennates and flagellates represented
      90% of total phytoplankton abundance. In the phytoplankton fraction (cells > 30
      microm), diatoms were the most abundant group, and Skeletonema costatum (32%)
      dominated. In nannophytoplankton (cells < 30 microm), Chaetoceros (23.7%) was the
      most abundant taxon, followed by flagellates (23%) and Cylindrotheca closterium
      (13.1%). These results agree with previous surveys and suggest that a typical net
      phytoplankton community persist through time in the Punta Morales zone. The
      number of nannophytoplankton fraction cells varied seasonally and suggests
      quantitative changes in species abundance, with possible modifications of
      cellular size or chain length in filamentous species. The codominance between S.
      costatum and Chaetoceros spp. during the rainy season suggested the ocurrence of
      an early ecological sucession, and nutrients could be the factor generating such
      population changes.

PMID- 15264518
TI  - [Red tide bloom produced by Lingulodinium polyedrum (Peridiniales, Dinophyceae)
      in Bahia Culebra, Papagayo Gulf, Costa Rica].
AB  - This is the first record of the dinoflagellate Lingulodinium polyedrum in a red
      tide bloom in the North Pacific coast of Costa Rica. The sample was collected on
      April 2000 at Culebra Bay, Gulf of Papagayo, from a patch of aproximatly 2000 m2,
      which produced a red discoloration of the water and a peculiar strong odor. This
      species produces spherical hypnocysts that may remain for decades when dark or
      anoxic conditions are present; L. polyedrum had been associated with the
      production of paralyzing toxins such as saxitoxins and yessotoxins. A second
      smaller patch was observed close Panama beach, into the bay, where we found seven
      puffer fish (Diodontidae) and two lobsters dead in the sand. It is important to
      develop a monitoring program to identify seasonal behavior of this species and
      ameliorate its impact on coastal human communities.

PMID- 15264519
TI  - Mollusks of Manuel Antonio National Park, Pacific Costa Rica.
AB  - The mollusks in Manuel Antonio National Park on the central section of the
      Pacific coast of Costa Rica were studied along thirty-six transects done
      perpendicular to the shore, and by random sampling of subtidal environments,
      beaches and mangrove forest. Seventy-four species of mollusks belonging to three
      classes and 40 families were found: 63 gastropods, 9 bivalves and 2 chitons,
      during this study in 1995. Of these, 16 species were found only as empty shells
      (11) or inhabited by hermit crabs (5). Forty-eight species were found at only one
      locality. Half the species were found at one site, Puerto Escondido. The most
      diverse habitat was the low rocky intertidal zone. Nodilittorina modesta was
      present in 34 transects and Nerita scabricosta in 30. Nodilittorina aspera had
      the highest density of mollusks in the transects. Only four transects did not
      clustered into the four main groups. The species composition of one cluster of
      transects is associated with a boulder substrate, while another cluster of
      transects associates with site. Two clusters were not associated to any of the
      factors recorded. Some species were present in previous studies but absent in
      1995, while others were absent in the previous studies but found in 1995. For
      example, Siphonaria gigas was present in 1995 in many transects with a relatively
      high density, but absent in 1962, probably due to human predation before the
      establishment of the park. Including this study, a total of 97 species of
      mollusks in three classes and 45 families have been reported from Manuel Antonio
      National Park. Sixty-nine species are new reports for the area: 53 gastropods, 14
      bivalves and 2 chitons. There are probably more species of mollusks at Manuel
      Antonio National Park, than the 97 reported here, because some areas have not
      been adequately sampled (e.g., deep environments) and many micro-mollusks could
      not be identified.

PMID- 15264520
TI  - Some Nereididae (Annelida: Polychaeta) from the Pacific Coast of Costa Rica.
AB  - Fifteen species of Nereididae (Annelida: Polychaeta) belonging to nine genera are
      reported from the subtidal and intertidal of the Pacific Coast of Costa Rica. A
      new species, Nereis costaricaensis, is described. Laeonereis brunnea Hartmann
      Schroder 1959 is removed from synonomy with L. culveri (Webster 1880) while
      Perinereis seridentata (Hartmann-Schroder 1959) is moved from the genus Neanthes
      based upon the presence of bar-shaped paragnaths on area VI of the proboscis. The
      presence of Neanthes micromma Harper 1979 is an extension of the range of this
      species from the Gulf of California and Neanthes roosevelti Hartman 1939 is the
      first record of this species since its description from the Galapagos. A
      taxonomic key to these nereidid species is included.

PMID- 15264521
TI  - Capitellidae (Annelida: Polychaeta) from the Pacific Coast of Costa Rica.
AB  - Eleven species of Capitellidae (Annelida: Polychaeta) belonging to eight genera
      are reported from the subtidal and intertidal of the Pacific Coast of Costa Rica.
      Three species, Mediomastus ambiseta, M. californiensis and Notomastus hemipodus,
      are found in highest abundances and are widespread in subtidal and intertidal
      environments. A taxonomic key to these species is included.

PMID- 15264522
TI  - Marine biodiversity of Costa Rica: the phyla Sipuncula and Echiura.
AB  - Fourteen species of Sipuncula belonging to 9 genera have been reported from Costa
      Rican waters, mostly from the Pacific coast. Three of these species are new
      records for Costa Rica (Phascolion strombus (Montagu 1804), Aspidosiphon
      (Aspidosiphon) muelleri Diesing 1851, and Aspidosiphon (Aspidosiphon) gracilis
      schnehageni (W. Fisher 1946)). One species of Echiura, Thalassema steinbecki
      Fisher 1946, in the order Echiuroinea, has been reported from the Pacific coast
      of Costa Rica.

PMID- 15264523
TI  - The effects of trawling on the benthic fauna of the Gulf of Nicoya, Costa Rica.
AB  - Four van Veen grab replicates where collected to sample macrofauna (organism
      retained on a 500 micron mesh sieve) at four stations in the Gulf of Nicoya,
      during October 24, 1997, January 16 and April 30, 1998. This information was used
      to search for any effects of trawling on the benthic fauna. Two stations where
      located in a trawled area, and two stations where in a protected area. Diversity
      (H') varied from 2.01 to 3.52 in the trawled area and from 2.13 to 2.78 in the
      protected area. Diversity was generally higher in the trawled area, and this was
      in contradiction to what we would have expected from other studies where the
      trend has been that trawling reduces diversity. Brittlestars and lancelets seemed
      to be the groups mostly harmed by the trawling, while amphipods where more
      abundant in trawled areas. The multivariate analyses did not reveal the patterns
      of faunal change as well as we hoped. This is surely because of our lack of more
      replicate samples. The multivariate analyses are easily confounded when few sites
      are analyzed. We have found differences in the type of fauna found in trawled and
      protected areas and, considering the differences in environmental variables in
      our stations and our lack of replication, this indicates that there are
      differences and a larger investigation is in order to reveal its magnitude.

PMID- 15264524
TI  - Abundance of Petrolisthes armatus (Crustacea: Porcellanidae) on a tropical
      estuarine intertidal rocky beach, Gulf of Nicoya estuary, Costa Rica.
AB  - Population of the porcellanid crab Petrolisthes armatus was studied on a rocky
      intertidal beach located at the Punta Morales peninsula in the mid upper Gulf of
      Nicoya estuary, Pacific coast of Costa Rica, from December 1997 to November 1998
      (14 dates). Horizontal plankton tows (280 micron mesh net) were also made to
      verify the presence of P. armatus larvae. Crabs were collected every 3 m along
      three 18 m long transects, at two sites on the beach, by placing a bottomless
      bucket fringed with canvas to prevent the organisms from escaping under the rim.
      A total of 15,382 P. armatus were collected. Only 146 (0.95%) crabs had a
      carapace length longer than 10 mm, and 8995 (58.5%) were in the size range of 2
      to 4.5 mm. The remaining crabs 6241 (40.5%) were in the size range of 4.6 to 10
      mm. Male and female P. armatus were represented by 2777 and 3518 individuals
      respectively, with a sex ratio of 1:1.26. Ovigerous females were found at all
      dates and included 2937 individuals (83% of females). Plankton tows yielded only
      73 larvae of P. armatus (Zoea 1), with a density of 1.2 larvae/m3. No
      statistically significant seasonal trends in the population of this species were
      detected. P. armatus appears to reproduce continuously the year around in Punta
      Morales, and some peaks of abundance were present during the dry and rainy
      seasons. These trends are similar to trends reported for other crustacean species
      in the Gulf of Nicoya.

PMID- 15264525
TI  - El Nino 1997-1998 impact on the plankton dynamics in the Gulf of Nicoya, Pacific
      coast of Costa Rica.
AB  - The impact of the El Nino 1997-1998 phenomenom on plankton dynamics was studied
      during 1997 at the Punta Morales estuary, Gulf of Nicoya, Pacific coast of Costa
      Rica. The study covered dry season/transition and the rainy season. Phytoplankton
      (microphytoplankton > 30 microm and nanophytoplankton) were collected at two
      depths (50 and 10% light incidence) using a 5 L Niskin bottle, and samples taken
      to determine chlorophyll a. Temperature, salinity, oxygen, and Secchi depth were
      measured. Horizontal sub-surface zooplankton hauls were conducted with a conic
      zooplankton net of 0.49 m diameter and 280 microm mesh width, supplied with a
      flowmeter. Surface sea water temperature average was 29.9 +/- 0.9 degrees C, with
      a maximum of 31.5 degrees C in April and a minimun of 28 degrees C in March and
      October. Chlorophyll a concentration (phytoplankton net) averaged 3.1 +/- 1.7
      mg/m3, with higher values during the rainy season and lower values during the
      transition. Nanophytoplankton chlorophyll a concentration averaged 2.5 +/- 1.2
      mg/m3, with a maximum during the transition season. For both fractions there were
      significant differences between transition and rainy seasons, and for
      nanophytoplankton between dry and transition seasons (p < 0.05). In the last
      case, differences were explained by temperature. Herbivorous copepods dominated
      the abundance and biomass of zooplankton, with a biomass maximun of 167.3 in
      October and a minimun of 7.1 mg DW/m3 in December. These values are higher than
      those found some years ago in the same zone and those reported for some places in
      the Caribbean. The El Nino 1997-1998 phenomenon in the plankton dynamics appears
      to have produced a change in the phytoplankton structure. This is the first
      attempt to evaluate the possible impact of El Nino on the plankton dynamics of
      the Pacific coast of Central America.

PMID- 15264526
TI  - [Marine biodiversity of Costa Rica, the microcrustacea: Copepoda (Crustacea:
      Maxillopoda)].
AB  - This report is part of a series that summarizes the species and localities of
      Costa Rican marine taxa. A review of the literature on copepods, both pelagic and
      benthic for the Pacific and Caribbean coast of Costa Rica, includes eighty
      species. Sixty seven pelagic species have been found, distributed between sixteen
      calanoid, one cyclopoid, three harparticoid and four poecilostomatoid families.
      Moreover, thirteen benthonic species distributed into six families, all
      harparticoids, are reported. Among the pelagic families, Pontellidae has six
      species, while Paracalanidae and Eucalanidae had five each. Other families, like
      Calanidae, Pseudodiaptomidae and Acartiidae had four species and most families
      only one. Forty five species are reported only for the Pacific coast, thirteen
      for the Caribbean coast, only nine species occurred in both coasts; being a
      direct consequence of the more intensive research effort in the Pacific. Pelagic
      copepod biodiversity reflects different oceanographic conditions in both coasts.
      Typical estuarine species were found in the lower region of the Gulf of Nicoya,
      while a mixture of estuarine and oceanic species were found in Golfo Dulce.
      Diversity in the Caribbean, specially at the Cahuita coral reef is lower in
      comparison with the copepod diversity found in other regions in the Caribbean
      sea. This may be due to the high sediment resuspension rate characteristic of the
      Cahuita coral reef, which could affect the reproduction of many holozooplankters,
      specially copepods. Although sixty seven pelagic copepod species appears to be in
      low numbers, in terms of specific biodiversity it is as high when compared to
      numbers found in other tropical areas. Thirteen species are reported in the
      literature, all harparticoids. Five species, three sub-species and one genera
      were new to science. Balacopsylla is reported for the first time from a
      neotropical regions, while the genus Karllangia, represented by two coexisting
      species in the Caribbean coast, belong to a few circumtropical-subtropical
      genera. The most diverse family was Tetragonicipitidae. This is the first effort
      to summarize the available information about the biodiversity of marine copepods
      for Costa Rica's coasts.

PMID- 15264527
TI  - [The diversity and distribution of the cetaceans of Costa Rica (Cetacea:
      Delphinidae, Physeteridae, Ziphiidae y Balaenopteridae)].
AB  - The first complete checklist of Costa Rican cetaceans is presented with a total
      of 28 species (35% of the group's world diversity). Most of the species occur in
      the Pacific Ocean (89%) and most are considered oceanic (57%), common (54%) and
      resident (68%). The known distribution and status of each species are also
      provided.

PMID- 15264528
TI  - [Variation of thermohaline properties in the Nicoya Gulf, Costa Rica].
AB  - The time-space behavior of thermohaline properties of the water masses in the
      Gulf of Nicoya, a tropical estuary in the Costa Rican Pacific coast, was studied
      by sampling monthly from April 1992 to April 1993. The saline field has a
      seasonal maximum during April, a month before the maximum temperature is
      observed. Minimun values were observed during October and November, in the rainy
      season. A defined surface saline front is located towards the east of Negritos
      Islands; it is produced by the interaction of freshwater from the Tarcoles River
      and the oceanic waters that enter through the occidental coast of the gulf. The
      vertical distribution of temperature and salinity indicates a gulf whose internal
      area is highly stratified in the rainy season, and much less stratified, or even
      well mixed in the dry season. The outer area of the Gulf is stratified throughout
      the year.

PMID- 15264529
TI  - Seawater temperature measured at the surface and at two depths (7 and 12 m) in
      one coral reef at Culebra Bay, Gulf of Papagayo, Costa Rica.
AB  - Superficial seawater temperature (SST) and at two depths (7 and 12 m) were
      measured non-continuously during the study of the corals and coral reefs of
      Culebra Bay (1993-1996). SST showed seasonal variations of approximately 4
      degrees C. The highest average temperatures (27.0 +/- 0.1, range 23-29 degrees C)
      were during the rainy season from May to November and the lowest (22.9 +/- 0.3
      degrees C, 15.5-29 degrees C) during the dry season from December to April. Cold
      fronts with 2-3 degrees C differences in SST frequently pass into the bay and
      remain there for several hours according to the tidal cycles. Differences of
      approximately 3 degrees C between SST and the bottom (5-10 m depth) were usually
      found, particularly at locations where bottom topography and tidal circulation
      produced tidal bores. The average temperatures recorded by data loggers placed at
      7 and 12 m depth on a coral reef at the outer shores of Culebra Bay, were 27.1 +/
      0.02 degrees C (20.5-31.6 degrees C) and 25.8 +/- 0.04 (9.9-31.5 degrees C)
      respectively. The seasonal pattern of higher and lower temperatures corresponds
      respectively to the rainy and dry season of the northern Pacific coast of Costa
      Rica. Water temperature at 12 m was < 14 degrees C for some hours during an
      upwelling event whilst minimum temperatures at 7 m were > or = 22 degrees C.
      Negative temperature anomalies coincided with an increase of the NE-E winds
      intensity and there is a lunar and tidal component which influence diumal
      variations of temperature. These results suggest that coral reefs built by
      branching species (e.g. Pocillopora spp.) in Culebra Bay could be limited by both
      the influence of cold fronts and by seasonal upwellings which affect negatively
      those coral species, as reported for other locations in the tropical eastern
      Pacific.

PMID- 15264530
TI  - [The bathymetry of Coco's Island, Costa Rica].
AB  - The bathymetry of Coco's Island (UNESCO Natural and Cultural World Patrimony),
      located approximately 500 km from the Pacific coast of Costa Rica, is not well
      known. It has a high marine biodiversity and also represents a meeting site for
      many species traveling throughout the Pacific Ocean. The insular shelf is
      irregular in extension and also in bathymetric features. The northeast limit is
      defined by the 109.8-128.1 m contours (60-70 fathoms) while the 183 m contour
      (100 fathoms) practically defines the rest of the island, from which the depth
      gradient is steep. The maximum extension is to the northeast with a longitude of
      13 km. In this context the present limits of the marine park (5 km), are
      insufficient to protect the whole insular shelf. Current regulation should be
      modified to prevent fishing activities less than 15 km from the Island.

PMID- 15264531
TI  - [Fifty years of geomorphologic change in Damas Island, Quepos, Costa Rica].
AB  - Fifty years of geomorphologic change in Damas Island, Quepos, Costa Rica, were
      studied from a photographic record that is available since 1947. Coastal dynamics
      were accelerated by the El Nino Phenomenon in 1997 which was simultaneous with
      the August-September astronomical tide, one of the highest in the 4-5 year cycle.
      Additionally, waves with high energy were present in some periods of these
      months. Processes were enough to break the island in two blocks and to initialize
      erosion and transport sediment that continues to date. The frequency of tropical
      storms and the wave energy will be greater in the next years increasing sediment
      instability processes in parts of the island. Two topographic profiles have shown
      that the island is not in equilibrium and that adding all the possible
      mareographic components it will be prone to continued erosion. The marine
      habitats around the island should be changing because the fresh and salt water
      input has been modified, specially because alteration in the Parrita and Paquita
      hydrological river basins, and its effects on the sediments of this system.

PMID- 15264532
TI  - [Tectonic survey of the Central Pacific coast of Costa Rica ].
AB  - Three fossil coral samples (Pocillopora elegans and Pocillopora damicornis) were
      collected from a beachrock in Puerto Escondido, central Pacific coast of Costa
      Rica. The age of the samples ranged from 1272+/-60 to 2010+/-60 years BP. They
      represent some of the few Holocene fossil corals known from the Pacific coast of
      the Americas. The uplift rate for the central Pacific coast of Costa Rica was
      calculated in 0.4 to 2.1 mm year(-1).

PMID- 15264533
TI  - [Some relations between the zones of beginning of the Central American Pacific
      and the Oceans Pacific and Tropical Atlantic].
AB  - In order to explore the influence of the surrounding tropical oceans on the
      Central American Pacific coast, a Transfer Function Model was fixed to Sea
      Surface Temperature Anomalies (SSTA) of the Gulf of Tehuantepec, Papagayo, Panama
      and Quepos time series. As independent variables the following were used: Nino
      3.4, Tropical North and South Atlantic indices. These models show that Nino 3.4
      has the most important influence over the region when compared with the influence
      of the other indices, having positive correlation with all the SSTA series. It
      shows an influence of this index on the relative termocline's depth in front of
      the Central American Pacific Coast.

PMID- 15264534
TI  - [A new species of Euphyllia (Scleractinia: Caryophylliidae) in the limestones of
      Barra Honda, Costa Rica].
AB  - A new species of scleractinian coral is described: Euphyllia donatoi. This is the
      first report of this genus from Central America. The outcrop is located on the
      north-west of Costa Rica. It consists of large colonies (1.2 m high by 0.5 m in
      diameter), from a patch reef which had a dendroid habit. They are part of a very
      distintive facies in a micritic limestones of the Barra Honda Formation
      (Paleogene). The finding is important because these are the only macrofossils
      found in Barra Honda Formation. The growth took place under unstable ecological
      conditions resulting in a low diversity autocthonous community. It probably
      developed in very shallow water with a high sedimentation rate.

PMID- 15264535
TI  - [Corals reef of the Upper Oligocene-Lower Miocene, of Turrialba, Costa Rica].
AB  - The outcrops at Jesus Maria (Turrialba, Cartago Province, Costa Rica) present
      limestone sequences 12 to 30 m thick (packstones: biolithites, biomicrites; and
      wackstones: biosparites, biomicrosparites), sandstones and conglomerates of Upper
      Oligocene-Lower Miocene age, correlated to the Punta Pelada Formation. The
      limestones are characterized by patch reefs with an irregular distribution and a
      reduced lateral extension (50 m), composed of corals (40%), calcareous algae and
      foraminiferans (30%), mollusks (20%), and in minor amounts fragments of
      barnacles, decapods, echinoderms and bryozoans. They consisted of low diversity
      communities possibly due to diverse geographical, geological and tectonic
      factors: a narrow continental shelf, very shallow and isolated environments, sea
      level fluctuations, and exposure to clastic sedimentation associated with
      intermitent volcanic activity. Equity was also low, with corals making up 40% of
      all macrofossils, and one species, Antiguastrea cellulosa, as predominant (80% of
      the corals present). These bioconstructions were developed in an open circulation
      lagoon environment with transitions, in several occasions, to shallower
      environments represented by elastic sediments.

PMID- 15264536
TI  - [The coral reefs and coral communities of Bahia Culebra , Pacific coast of Costa
      Rica: biological aspects, economic-recreational and diving activities].
AB  - The coral reefs (AC) and coral communities on basalts (CCB) or sand (CCA) of
      Bahia Culebra (Golfo de Papagayo, northern Pacific coast of Costa Rica), were
      compared with descriptors such as cover percentage, diversity, substrate
      topographical heterogeneity (I(H)), associated organisms and frequency of
      recreational-commercial diving activities on them. Sea urchin abundance and I(H)
      were similar among the three reefal environments. The AC had higher coral cover
      (ca. 40%) and total live cover (>50%). The CCB had higher macro and calcareous
      algae (>5%) and sponges (>2%). Associated organisms (>2%) and general diversity
      (0.6) were higher in the CCA. Branching coral species (Pocillopora spp.)
      accounted for >40% of total coral cover in the reefs, followed by massive species
      (ca. 30%). In the CCB, branching species contributed ca. 80% and massive ca. 19%,
      whilst in the CCA ca. 68% and ca. 29% respectively. This differences could be
      related with the substrate consolidation and ample depth range of coral
      communities. Most of the recreational dives were conducted at the CCB; only
      occasionally the CCA and AC are visited. Interviewed divers had a principal
      interest on fish and it is precisely at the CCB where highest fish diversity and
      biomass are observed. Commercial divers tend to prefer the CCB because of their
      abundance and distribution in the bay. At the outer littoral of Bahia Culebra,
      diversity of all taxa and live coral cover zonal distribution are generally
      higher. In addition to these descriptors, indexes that indicate the regional
      value of a particular reef or coral community is recommended. Coastal
      infrastructure is mainly concentrated at three areas of the bay; one of them
      harbors a rare Leptoseris papyracea reef (the only reported so far in the eastern
      Pacific) and the solely Costa Rican living population of the free living coral
      Fungia (Cycloseris) curvata. A resort marina will be built over this reef. A
      protection plan for this and other reefal environments of Bahia Culebra is urgent
      and must include the monitoring of environmental variables and coral health.

PMID- 15264537
TI  - Bleaching and mortality of reef organisms during a warming event in 1995 on the
      Caribbean coast of Costa Rica.
AB  - Coral reefs at the Caribbean coast of Costa Rica were affected during a bleaching
      event associated with the 1995 warming of the Western Caribbean. During doldrum
      weather in late August 1995, reef organisms at Parque Nacional Cahuita were 62%
      and 7.4% bleached and dead respectively, whilst 67.6% bleached and 8.2% died in
      the Refugio Nacional de Vida Silvestre Gandoca-Manzanillo. However, Cahuita had
      the highest mean number of bleached (257 +/- 51.1) and dead (30.5 +/- 5.6)
      colonies in the surveyed transects, and bleaching was observed down to a depth of
      20 m. The most affected species (>10% of dead colonies) were the hydrocoral
      Millepora complanata and the scleractinian corals Montastraea spp. at Cahuita,
      and Porites furcata, Porites porites and M. complanata at Gandoca-Manzanillo.
      Mean seawater temperature was between 30.5 and 31.1 degrees C (0-18 m depth)
      during four days of observation at the end of August 1995. Coral reefs of the
      Costa Rican Caribbean coast have shown a rapid decline during the last 20 years
      due to natural and anthropogenic disturbances. The effect of the 1995 warming
      added more pressure to the already deteriorated reefs.

PMID- 15264538
TI  - Effects of the 1991-92 El Nino on scleractinian corals of the Costa Rican central
      Pacific coast.
AB  - Coral communities on the central Pacific coast of Costa Rica were affected during
      the 1991-92 El Nino warming event. More than 57% of all observed colonies at
      three localities (Parque Nacional Manuel Antonio, Punta Cambutal, and Parque
      Marino Ballena) were bleached. Mortality during this El Nino was much lower
      (approximately 9%) than in previous events. Psammocora spp. accounted for
      approximately 66% of dead corals, while massive (Porites lobota, Pavona spp.) and
      branching (Pocillopora spp.) for approximately 34%. Our results suggest that the
      observed bleaching in P. lobata was related to zooxanthellar densities and not to
      changes in pigment concentrations: only chlorophyll a varied between normally
      pigmented and bleached colonies at one locality (Ballena). Site differences in
      zooxanthellar densities or their pigment concentrations, may not be the result of
      the bleaching event itself, because a percentage of dead corals and zooxanthellar
      densities of bleached colonies seems to follow a trend with the exposure to tidal
      regimes and currents at each site. Local oceanographic conditions can be
      influencing the zooxanthellar densities and their response to the warming,
      together with intrinsic differences between colonies as well. The impact of this
      event can be considered serious given the short period of time that elapsed
      between El Nino related mortalities and the slow reefs recovery, the mode of
      reproduction of reef building species, and the anthropogenic-originated
      disturbances which affect the coral communities and reefs of the Costa Rican
      central Pacific coast.

PMID- 15264539
TI  - Spatial distribution of light and nutrients in some coral reefs of Costa Rica
      during January 1997.
AB  - The proximity of coral reefs to areas of present and future coastal development
      in Costa Rica highlights the need for assessing environmental conditions
      important to maintaining healthy corals. In January 1997 a survey of light
      penetration, inorganic nutrient concentrations, temperature, and salinity was
      conducted in the patch reefs of Bahia Culebra (Pacific Ocean) and on the
      Caribbean coast in the fringing reef at Parque Nacional Cahuita and near Limon.
      Temperature was 28 degrees C at all sites, and salinity ranged from 33 to 36 psu.
      Light attenuation coefficients ranged from 0.12 to 0.29 m(-1) in reef areas.
      Seawater nutrient concentrations were within the range of concentrations reported
      for tropical reef waters; combined NO3- and NO2- and PO4(3-) were each below 1
      microM. NH4+ ranged from 0.2 to 7 microM, representing a significant source of
      nitrogen. The ratio of total dissolved inorganic nitrogen to phosphate averaged
      27 for all reef waters. The high nitrate (3.6 microM) and light attenuation (0.95
      m(-1)) values from the surface waters of the La Estrella plume (Caribbean coast)
      show that this river represents a significant source of nitrogen and light
      attenuation for the neighboring reefs at Cahuita. This survey provides a useful
      baseline for future studies, which should monitor these important coastal coral
      reef areas during both wet and dry seasons.

PMID- 15264540
TI  - Biomass, productivity and density of the seagrass Thalassia testudinum at three
      sites in Cahuita National Park, Costa Rica.
AB  - The basic ecology of seagrass beds was investigated by comparing biomass,
      productivity and density of Thalassia testudinum (turtle grass) at three sites:
      Puerto Vargas, Punta Cahuita and Rio Perezoso, in Cahuita National Park, Limon,
      Costa Rica, over a two month period (March-April 1999). Above ground biomass,
      density, and productivity were highest in the Puerto Vargas site while Punta
      Cahuita had the least non-green above ground biomass was significantly lower in
      total biomass than Puerto Vargas. Punta Cahuita was distinguished by the largest
      grain size, a very hard substrate, and shallower water. Rio Perezoso, on the
      other hand, had extremely fine sediment and lower salinity, while Puerto Vargas
      was intermediate both in sediment size and environmental conditions. It appears,
      therefore, that higher biomass and productivity result from a combination of
      moderate environmental characteristics and an intermediate sediment size.

PMID- 15264541
TI  - Requiem for an eastern Pacific seagrass bed.
AB  - Few papers concerning seagrasses of the eastern Pacific have been published. This
      paper presents the first ecological data on the seagrass, Ruppia maritima, from a
      non-lagoonal setting in the eastern Pacific. A 5000 m2 patch formed by R.
      maritima, at Playa Iguanita, Bahia Culebra, Pacific coast of Costa Rica was
      studied. Plant density and leaf length of R. maritima were determined along two
      transects on different dates. Above and below ground biomass were calculated
      along one transect. Plant density ranged from 1590 to 8630 individuals m(-2)
      along the two transects, with means of 5990 +/- 1636 and 6100 +/- 1876 plants m(
      2) for transect 1 and 2, respectively. Longest leaf length per plant varied
      between 0.5 and 23.0 cm. Leaf biomass (LB) ranged from 10 to 97 gm(-2), and root
      rhizome biomass (RB) from 31 to 411 gm(-2), resulting in RB:LB ratios of 3.07 to
      15.27. Total biomass at Bahia Culebra was lower than at tropical lagoons on the
      Pacific coast of Mexico, but higher than in the Gulf of Mexico. The below ground:
      above ground biomass ratio was much higher at Bahia Culebra than at other sites
      on the Pacific coast of Mexico and the Gulf of Mexico. Another seagrass present
      at Bahia Culebra was Halophila baillonii, with low densities on the deepest
      section of the patch. At least 44 invertebrate species associated with the
      seagrass bed have also been identified. The patch at Playa Iguanita and other
      sites within Bahia Culebra, as well as their associated organisms, disappeared
      after a severe storm in June 1996. No seagrasses have been found in the area or
      in any other location on the Pacific coast of Costa Rica since then.

PMID- 15264542
TI  - Planktonic primary production in a tidally influenced mangrove forest on the
      Pacific coast of Costa Rica.
AB  - The seasonal variation of planktonic primary productivity was measured during one
      year in the main channel in the interior part of the mangrove forest of the
      Estero de Morales (Estero de Punta Morales), a mangrove system located in the
      Golfo de Nicoya at the Pacific coast of Costa Rica. Samples were incubated at the
      surface, 0.5 m and 1.0 m depth and the "light and dark bottle technique" was
      employed. The annual gross primary productivity (PPg) was 457 and the net primary
      productivity (PPn) was 278 g C m(-2) a(-1). Daily PPg ranged from 0.29 to 3.88
      and PPn from 0.12 to 2.76 g C m(-2) d(-1). The highest rates observed in May and
      September were due to red tide blooms. The seasonal variation of primary
      productivity inside the mangrove forest depends closely on the PP in the adjacent
      area of the upper Golfo de Nicoya. Obviously the PP was light-limited since the
      compensation depth in the ebb current was found at only 1 m depth. In the flood
      current it was somewhat deeper. The planktonic primary productivity inside the
      mangrove forest was completely restricted to the open channels. A simultaneous
      measurement demonstrated that PPn of the phytoplankton could not take place under
      the canopy of the mangroves. Additional studies on the time course of the oxygen
      concentration in the mouth of the main channel over 24 hrs demonstrated a
      relation between the O2 and the tidal curves. The ebb current had always lower O2
      concentrations than the flood current, regardless of the time of the day. The
      difference to the foregoing high tide, however, was much smaller when the low
      tide occurred during the day. This indicates that under the canopy the net
      primary production and hence O2 liberation of the attached macro- and microalgae,
      together with the high PPn of the phytoplankton in the channels, helped the
      oxygen concentration not to decrease as far as during the night. Nevertheless it
      shows that the consumtion of organic material in the submersed part of the
      mangrove forest exceeds always its production.

PMID- 15264543
TI  - The annual cycle of primary productivity in a tropical estuary: the inner regions
      of the Golfo de Nicoya, Costa Rica.
AB  - A one year cycle of primary productivity (PP) was studied using the "light and
      dark bottle" technique in the Golfo de Nicoya, located at 10 degrees N and 85
      degrees W at the Pacific coast of Costa Rica. Samples were always incubated at 0,
      1, 2, 3 and 4 m depth for 5 hrs from 8:30 till 13:30. The measurements were
      performed twice per month, first around high tide and one week later at low tide
      to account for tidal influences. This routine study was supplemented by special
      measurements about regional and short-term variations of primary productivity
      using the 14C-method, which mainly served to account for the shortcomings of the
      routinely employed incubation technique. The upper Golfo de Nicoya is an
      extremely productive, phytoplankton dominated estuarine system with an annual
      gross PP of 1037, a net PP of 610 and a community respiration of 427 g C m(-2) a(
      1). Highest monthly PP values occurred during the dry season and at the beginning
      of the rainy season. Peaks in primary productivity coincided with massive blooms
      of red tide forming algae. Internal biological dynamics, estuarine circulation
      and land run-off are the most important nutrient sources. High water turbidity
      reduces the euphotic layer to 4-5 m depth, making the underwater light regime the
      rate limiting factor. On an annual basis, 41% of the organic carbon produced in
      the system is already consumed in the euphotic layer. Considering the entire
      water column (mean depth at mean tidal water level is around 7.7 m) 79% is
      consumed in the pelagial. Taking into account the organic material consumed and
      stored in the sediments the carbon budget of the upper gulf is probably balanced.
      Since, however, the system receives a considerable amount of organic material
      from its terrestrial surroundings (especially from the mangrove forests), a
      surplus of organic carbon is exported from the upper Golfo de Nicoya, which
      enhances the overall water productivity of the lower gulf and the adjacent area.

PMID- 15264544
TI  - [Juvenile fish in a tidal pool, Terraba-Sierpe Forest Reserve, Puntarenas, Costa
      Rica].
AB  - Juvenile fish were sampled with a 10 m long net in a tide pool (17,000 m2) on the
      West margin of Boca Guarumal, Terraba-Sierpe Forest Reserve, Puntarenas, Costa
      Rica, from October 1992 through January 1994. Water temperature and surface
      salinity were recorded in each visit. The specimens were fixed in 5% formaldehyde
      and preserved in 70% ethanol. Abundance and size data were pooled based on
      precipitation, a main ecological influence in the Reserve. A total of 13,494
      individuals from 18 species were captured. Eucinostomus currani, Gobionellus
      sagittula, Diapterus peruvianus, Agonostomus monticola and Atherinella sp.
      represented more than 97% of the captures. Although many species presented the
      tendency of concentrating during the dry season, significant differences in
      temporal abundance were found. The fish entered the estuary when their body
      length was between 20 and 60 mm.

PMID- 15264545
TI  - [Abundance and morphometry of tuberculosa Anadara and A. similis (Mollusca:
      Bivalvia) in the Manglar de Purruja, Dulce Gulf, Costa Rica].
AB  - The density, population, length, yield and sex proportion of the mollusks Anadara
      tuberculosa and A. similis were studied in Bahia de Golfito, Golfo Dulce, Pacific
      coast of Costa Rica from February 1998 to February 1999. A. tuberculosa was more
      abundant (0.9 units m(-2)), than A. similis (0.2 units m(-2)); the highest
      abundance was found at the canal mouths. The average lengths were 43.3 mm for A.
      tuberculosa and 42.8 mm for A. similis (both under the Costa Rican legal minimal
      length for exploitation: 47 mm). Maximum lengths were measured in the middle and
      upstream Canal Mayor, respectively: 43.0 mm and 43.4 mm. The correlation between
      length and fresh weight was 0.81 (Pearson). The average total weights were 26.2 g
      for A. tuberculosa and 19.1 g for A. similis. The condition index (a meat yield
      measurement) was higher in A. similis (21.2%) than in A. tuberculosa (17.2%). The
      maximum yield for both species lies in the 31-35 mm range. The male ratio was
      43.7%. A species recovery plan is urgent because these results suggest both a
      decrease in density and illegal exploitation.

PMID- 15264546
TI  - [The mangrove and others vegetation associations in de Gandoca lagoon, Limon,
      Costa Rica].
AB  - Six plant associations were identified at Gandoca Lagoon by photointerpretation
      and field verification: a) mangroves, b) palm trees swamp, and palm trees with
      Acrostichum aureum and A. danaefolium, c) mixed palm trees, d) very humid
      tropical rain forest, and e) tropical beach vegetation. The mangroves cover 12.5
      ha surrounding the lagoon and extend 2 km up the Gandoca River. Rhizophora mangle
      (red mangrove) was the dominant species, with Avicennia germinans (black
      mangrove), Laguncularia racemosa (white mangrove) and Conocarpus erectus
      (buttonwood) also present. Moving inland the mangroves grade into a tropical rain
      forest. Gandoca, the largest and best preserved mangrove of Caribbean Costa Rica,
      tripled its area from 1976 to 2000. Possible causes include sedimentation and the
      Limon earthquake, which may have subside the lagoon area.

PMID- 15264547
TI  - [Mangrove characterization of Central America with remote sensors].
AB  - Satellite images were used to study the mangrove distribution patterns in two
      different climatic regions of Central America: Gulf of Fonseca in Honduras-El
      Salvador and Sierpe-Terraba in Costa Rica. The Gulf of Fonseca has higher
      temperature and solar radiation, and lower precipitation, which can explain the
      higher structural development and species mixing of the Sierpe-Terraba mangrove.
      In the latter the transition between species or between heights in the same
      species is clear. The automatic classification made by the Geographic Information
      System (IDRISI) fits well the field mangrove distribution, but it was necessary
      to regroup some subdivisions that represent the same land use as identified by
      transects and an aerial video. Mixed species and clouds produced less
      satisfactory results in Sierpe-Terraba indicating a need for better satellite
      image resolution.

PMID- 15264548
TI  - The effect of elevated temperature on the toxicity of the laboratory cultured
      dinoflagellate Ostreopsis lenticularis (Dinophyceae).
AB  - Ostreopsis lenticularis Fukuyo 1981, is the major benthic dinoflagellate vector
      implicated in ciguatera fish poisoning in finfish on the southwest coast of
      Puerto Rico. Clonal laboratory cultures of O. lenticularis (clone 301) exposed to
      elevated temperatures (30-31 degrees C) for 33 and 54 days showed significant
      increases in the quantity of extractable toxin they produced as compared to their
      toxicities versus cells grown at temperatures of 25-26 degrees C. O lenticularis
      samples collected directly from the field following exposure to elevated
      temperatures for comparable periods of time also showed significant increases in
      extractable toxin. The increased toxicity of both field sampled and laboratory
      grown O. lenticularis exposed to elevated temperatures may result from the
      effects of elevated temperatures on their metabolism and/or the bacterial
      symbionts found associated with these microalgae. The number of bacteria
      associated with cultured O. lenticularis exposed to elevated temperatures was
      significantly reduced. Increased toxin recovery from O. lenticularis exposed to
      elevated temperatures may have resulted from the direct effect of temperature on
      toxin production and/or the reduction of Ostreopsis associated bacterial flora
      that consume toxin in the process of their growth. This reduction in the quantity
      of associated bacterial flora in temperature treated cultures may result in
      increased toxin recovery from O. lenticularis due to a reduction in the
      consumption of toxin by these symbiont bacteria.

PMID- 15264549
TI  - [Genetic and morphological characteristics of the populations of Cyprinodon
      dearborni (Atherinomorpha: Cyprinodontidae) in Chacopata and Laguna de los Patos,
      Venezuela].
AB  - Two populations of the fish Cyprinodon dearborni were compared, one from Laguna
      de Chacopata and the other from Laguna de los Patos, Cumana, Venezuela. The
      morphometric method of the Box Truss was used; the organisms were photographed
      with a digital camera. In the images 18 measures were made to each organism, with
      the MOCHA 1.2 program. The tendencies of morphologic variation among populations
      were analyzed by main components using STATGRAPHICS 2.0 and SHEAR programs. The
      first four main components in males and females explained 88% of the total
      variation. The components two, three and four separate the two populations based
      on the body form of the animals. For the electrophoretic study, 13 enzymatic
      systems were analyzed in starch gels. The variation and genetic distance were
      calculated with the program GENES 2.0. Differences were observed in the systems
      G6PDH, GPI; ES and GLUD, that which can be used as isoenzimatic markers. Genetic
      diversity of Chacopata (H = 0.086, p = 0.079) was higher than in Laguna de los
      Patos (H = 0.029, p = 0.028), but both are within the average in populations of
      fish. The two populations presented a Nei distance of 0.058. The genetic and
      morphologic differentiation suggests an incipient process of separation whose
      causes could be the ecological conditions of their habitat, or processes of
      vicariant speciation.

PMID- 15264550
TI  - Recent settlement trends in Panulirus argius (Decapoda: Palinuridae) pueruli
      around St. Thomas, U.S. Virgin Islands.
AB  - Puerulus settlement of the western Atlantic spiny lobster, Panulirus argus, was
      monitored using modified Witham collectors from December 1996 to March 1998 at
      seven sites around St. Thomas, U.S. Virgin Islands. A total of 605 pueruli were
      collected from 553 samples for a catch per unit effort (CPUE) for all sites of
      1.09 pueruli. The greatest settlement occurred on sites within a recently
      declared marine reserve, which had an overall CPUE of 1.77 pueruli. Settlement in
      non-reserve sites was much lower with an overall CPUE of 0.31 pueruli. Pueruli
      recruitment declined 67% at inshore sites and 53% at offshore sites between July
      1992 - April 1994 and February 1997 - March 1998. Also, only 10% of months
      sampled in 1997-98 had a CPUE > 0.5 compared to 55% in a previous study in 1992 -
      1993. Despite the decline in pueruli CPUE in 1997-98 compared to 1992-94, the
      commercial lobster catch in the 2000-01 fishing season, and by inference the
      adult lobster population (legal lobster size in the US Virgin Islands is > or =
      3.5 cm carapace length), remained stable.

PMID- 15264551
TI  - Three scleractinian coral diseases in Dominica, West Indies: distribution,
      infection patterns and contribution to coral tissue mortality.
AB  - Coral diseases have been documented in many areas of the Caribbean, but studies
      in the eastern Caribbean region have been lacking. The prevalence, distribution
      patterns and contribution to the mortality of coral tissue by black band discase
      (BBD), white plague (WP) and dark spots disease (DSD) were examined at five reef
      sites along the west coast of Dominica. 185 of the 325 diseased colonies recorded
      between March and August 2000, in a survey area of 5884 m2, were WP. This disease
      contributed to 89% of the total 4.08 m2 of tissue mortality caused by diseases
      during the survey period. WP also affected the largest average tissue surface
      area (relative to colony size) per colony and exhibited the largest average
      tissue loss per infection when compared to BBD and DSD. The species most
      susceptible to WP and BBD in Dominica differed from most other described
      Caribbean locations with Siderastrea siderea being most susceptible. S. siderea
      was also the only species noted to be susceptible to DSD. Measurements of colony
      size revealed that each disease affected the larger colonies of some coral
      species. Comparisons between disease prevalence at each site and various physical
      parameters, including temperature, wave height, depth, and current patterns, did
      not exhibit significant correlations. The lack of a direct correlation between
      temperature and disease prevalence indicates that there are other seasonal
      factors contributing to the higher prevalence of diseases recorded during the
      summer months in Dominica. WP prevalence at each site was positively correlated
      to the relative species abundances of the species most susceptible to WP. This
      was the dominant factor in determining site-specific disease densities of this
      disease and may therefore be a valuable predictive and management tool. There
      were no correlations between BBD or DSD and the relative abundances of
      susceptible species. The spatial distribution patterns of WP, BBD and DSD were
      clustered, which is a distribution pattern that suggests an infectious disease.

PMID- 15264552
TI  - White plague disease outbreak in a coral reef at Los Roques National Park,
      Venezuela.
AB  - Coral diseases have been reported as a major problem affecting Caribbean coral
      reefs. During August 2000, a coral mortality event of White Plague Disease-II
      (WPD-II) was observed at Madrizqui Reef in Los Roques National Park, Venezuela.
      This disease was identified as the major cause of coral mortality, affecting 24%
      of all colonies surveyed (n = 1 439). Other diseases such as Black Band Disease
      (BBD), Yellow Blotch Disease (YBD), Dark Spots Disease (DSD) and White Band
      Disease (WBD) were also recorded, but showed a lower incidence (0.14-0.97%). Two
      depth intervals, D1 (5.5-6.5 m) and D2 (9-9.5 m) were surveyed with two sets of
      three band transects 50 x 2 m long, placed parallel to the long axis of the reef.
      All healthy and injured corals, along each band transect, were counted and
      identified to species level. Additionally, all diseases and recent mortality that
      were still identifiable on each colony also were recorded. The incidence of
      colonies affected by WPD-II ranged from 12.8 to 33% among transects, where
      thirteen species of scleractinian corals showed several degrees of mortality. The
      species most affected were Montastraea annularis (39.13%), M. faveolata (26.67%),
      M. franksi (9.86%), Stephanocoenia intersepta (7.25%), Colpophyllia natans
      (6.96%), Diploria labyrinthiformis (2.99%), Mycetophyllia aliciae (2.03%), M.
      cavernosa (1.74%), and D. strigosa (1.45%). WPD-II was more common in the deeper
      strata (9-9.5 m), where 63% of the surveyed colonies were affected, although the
      disease was present along the entire reef. Presently, it is imperative to
      determine how fast the disease is spreading across the reef, how the disease
      spreads across the affected colonies and what the long-term effects on the reef
      will be.

PMID- 15264553
TI  - Monitoring the coral disease, plague type II, on coral reefs in St. John, U.S.
      Virgin Islands.
AB  - In July 1997, conspicuous white patches of necrotic tissue and bare skeleton
      began to appear on scleractinian corals in several bays around St. John, US
      Virgin Islands. Analysis of diseased coral tissue from five different species
      confirmed the presence of a Sphingomonas-like bacterium, the pathogen for plague
      type II. To date, 14 species of hard corals have been affected by plague type II
      around St. John. This disease was monitored at Haulover and Tektite Reefs at
      depths of 7-12 meters. The study site at Tektite Reef has > 50% cover by
      scleractinian corals with 90% of hard corals being composed of Montastraea
      annularis. Monthly surveys at Tektite Reef from December 1997 to May 2001
      documented new incidence of disease (bare white patches of skeleton) every month
      with associated loss of living coral and 90.5% of all disease patches occurred on
      M. annularis. The frequency of disease within transects ranged from 3 to 58%, and
      the area of disease patches ranged from 0.25 to 9000 cm2. The average percent
      cover by the disease within 1 m2 ranged from 0.01% (+/- 0.04 SD) to 1.74% (+/-
      9.08 SD). Photo-monitoring of 28 diseased corals of 9 species begun in September
      1997 at Haulover Reef revealed no recovery of diseased portions with all necrotic
      tissue being overgrown rapidly by turf algae, usually within less than one month.
      Most coral colonies suffered partial mortality. Very limited recruitment (e.g.,
      of Agaricia spp., Favia spp. and sponges) has been noted on the diseased areas.
      This coral disease has the potential to cause more loss of live coral on St. John
      reefs than any other stress to date because it targets the dominant reef building
      species, M. annularis.

PMID- 15264554
TI  - Response of Millepora alcicornis (Milleporina: Milleporidae) to two bleaching
      events at Puerto Morelos reef, Mexican Caribbean.
AB  - Two naturally occurring colonies of Millepora alcicornis were monitored during
      1997 and 1998, both years in which this species bleached in the Mexican
      Caribbean. One colony (HL) was naturally exposed to a high light environment and
      another nearby colony (LL) was exposed to 5.9 times lower light levels due to
      shadowing by a pier. For 10 days in August 1997, seawater temperatures in the
      surrounding reef lagoon rose up to 1.5 degrees C above the 6-year August average.
      The HL colony bleached to white during this period, whereas, the LL colony
      remained dark-brown colored. The HL colony recovered its normal dark-brown
      coloration (reversible bleaching) within several weeks, during which time the
      seawater temperatures returned to average. The following year, for 10 days,
      seawater temperatures rose up to 3 degrees C above the 7-year August average and
      both colonies bleached to white and neither colony recovered (irreversible
      bleaching). Both colonies were rapidly overgrown by algae and hydroids and, as of
      June 2003, no recovery has taken place. Prior to the 1997 bleaching, experiments
      using solar radiation showed that the quantum yield of photosystem II charge
      separation of branches from HL and LL colonies were affected for several hours by
      exposure to ultraviolet radiation (UVR, 280 to 400 nm), but recovered by the same
      evening, suggesting that UVR does not have long-term effects on photochemistry in
      M. alcicornis. In situ effective quantum yield of photosystem II charge
      separation (deltaF/Fm') measurements before the 1998 bleaching event indicate
      that both colonies were healthy in terms of the physiological status of their
      endosymbionts. During and after the 1998 bleaching event, both colonies showed a
      reduction in deltaF/Fm' and consequently an increase in excitation pressure on
      photosystem II. The data suggest that temperature is not the only factor that
      causes bleaching and that solar radiation may play an important role in coral
      bleaching.

PMID- 15264555
TI  - Comparisons of the 1995 and 1998 coral bleaching events on the patch reefs of San
      Salvador Island, Bahamas.
AB  - Coral patch reefs around San Salvador Island, Bahamas have been monitored with
      the aid of Earthwatch volunteers three times a year since 1992. During that
      period two significant mass bleaching events occurred: autumn 1995, and late
      summer 1998. Elsewhere in 1995, bleaching was caused by higher-than-normal summer
      sea temperatures; in San Salvador, however, temperatures were normal. In 1998 a
      prolonged period of higher-than-normal sea temperatures preceded bleaching on San
      Salvador and worldwide. During the 1995 event, one of the monitored reefs had
      twice the percentage of coral colonies bleached as the other two. Bleaching was
      more evenly distributed among the reefs during the 1998 event. In 1995 Agaricia
      agaricites was significantly more affected than other coral species, with almost
      50% of all its colonies showing bleaching. Bleaching was more evenly spread among
      coral species in 1998, with five species showing bleaching on more than 40% of
      their colonies. Bleaching began on Millepora as early as August during the 1998
      event and progressed to other species through the remainder of the autumn. In
      1995 bleaching was not seen until late autumn and appeared to impact all affected
      species at about the same time. Recovery from the 1995 event was complete: no
      coral death or damage above normal background levels were seen. In the 1998
      event, all Acropora cervicornis on the monitored reefs died and A. palmata was
      severely damaged. Millepora sp. lost almost half of their live tissue, and
      Montastraea sp. showed significant tissue damage following this event.
      Phototransect analysis suggests that more than 20% of total live tissue on
      affected species died during the 1998 event. A. cervicornis has demonstrated no
      re-growth from 1998 to 2000 on monitored reefs. Monitoring has suggested
      significant differences in causes and courses in these two events.

PMID- 15264556
TI  - Behavioral and ecological correlates of foureye butterflyfish, Chaetodon
      capistratus, (Perciformes: Chaetodontidae) infected with Anilocra chaetodontis
      (Isopoda: Cymothoidae).
AB  - We observed the behavior and ecology of Chaetodon capistratus infected and
      uninfected with the ectoparasitic isopod Anilocra chaetodontis to assess whether
      there may be parasite induced alterations in host biology, host defenses against
      infection, and/or pathology related to infection. We also examined habitat
      related differences in infection rates. Infected fish had higher rates of
      interaction with conspecifics and spent more time in low flow environments (which
      might improve transmission of juvenile parasites to new hosts). Butterfly fish
      without isopods were chased more frequently by damselfishes, fed more, and had
      larger territories. Time spent near conspecifics, and fish condition and
      gonadosomatic index did not vary between infected and uninfected fish. These
      results suggest that foureye butterfly fish behavior is altered by the isopod
      parasite in order for the isopods to more easily gain mates or transmit offspring
      to new hosts.

PMID- 15264557
TI  - [Diameter-weight relationship and chromatic proportion of the sea urchin
      Lytechinus variegatus (Echinoidea: Toxopneustidae) in the islands of Margarita
      and Cubagua, Venezuela].
AB  - In Margarita and Cabagua Islands, Venezuela, the sea urchin Lytechinus variegatus
      is consumed as food but few studies concern its biology. Between January 1999 and
      September 2000, 25 localities of Margarita and Cubagua islands we visited to
      determinate the relationship between diameter and weight of living urchins
      according to their coloration green or white. A total of 5 066 urchins (3 421
      captured in Margarita and 1 645 in Cubagua) were measured. There is no
      significant difference in the weight-diameter relations of green or white sea
      urchins of both islands. The weight-diameter equation is P = 0.00246 D252.
      Utilizing a quadrant (0.5 x 0.5 m) monthly samples of urchins living in a 2 m2 of
      surface were taken to estimate the abundance of the specimens according their
      color (N = 6 948 urchins). The green urchins were more abundant than the white
      urchins, in a 3:2 proportion.

PMID- 15264558
TI  - A survey of the epibiota of Eretmochelys imbricata (Testudines: Cheloniidae) of
      Mona Island, Puerto Rico.
AB  - Epibiotic organisms inhabiting non-nesting hawksbill sea turtles, Eretmochelys
      imbricata (Linnaeus, 1766), are described from Mona and Monito Islands, Puerto
      Rico. Epibiont samples from 105 turtles of shallow (< 40 m) water foraging
      habitats were collected and identified to the lowest possible taxon. This
      epibiotic assemblage consisting of at least 4 algal functional groups and 12
      animal phyla represents the greatest phylogenetic diversity for marine turtle
      epibiota. Six groups are considered new reports for marine turtles. Most epibiont
      colonization was found on posterior marginal scutes and under overlapping scutes.
      Ecological attributes of epibiota and their symbiosis with E. imbricata provide a
      tool to understand basi and epibiont populations.

PMID- 15264559
TI  - [RNA/DNA ratio as an index of physiological condition of Colossoma macropomum and
      Piaractus branchypomus (Pisces: Characiformes) during embryonic development].
AB  - We evaluated RNA/DNA ratio as an index of physiological condition during larval
      development of a hybrid between the fishes Colossoma macropomum (cachama) and
      Piaractus brachypomus (morocoto). The samples were obtained by induced
      reproductive technology and the eggs were maintained in acrylic conical incubator
      with a continuous waterflow. Embryonic development, from egg fertilization to
      cell division and hatch out, took 12 hours 20 minutes at 29.5 degrees C,
      dissolved oxygen contents of 6.0 ppm and pH 7.5. Nucleic acids quantification was
      determined by fluorometry with ethidium bromide and Hoechst 33258 dyes. We
      observed significant changes of RNA/DNA ratios during all stages of the embryonic
      larval development. Therefore, RNA/DNA relation is an useful technique to
      evaluate physiological condition in short period and could be utilized as
      nutritional condition and/or instantaneous growth for routine check to verify the
      health status in early life of cultivated species.

PMID- 15264560
TI  - [Population biology patterns of commercially important mollusks in Mexico].
AB  - The need to propose recommendations for the management of over 80 species of
      bivalves and gastropod mollusks exploited commercially in Mexico, led to look for
      trends on the population and reproductive biology in relation to prevailing
      environmental conditions of the habitats where they are exploited. The
      reproductive cycle, growth parameters for the von Bertalanffy equation, mortality
      and recruitment of 18 populations of 14 species from 13 localities are compared
      and related to ambient temperature, precipitation, evaporation, geomorphology,
      tides, and water salinity and temperature. Localities were classified as
      influenced by landmasses or with marine influence, with a desert or tropical
      humid climate. With restricted or continuous communication to oceanic waters and
      with or without freshwater runoff. The reproductive cycles were classified in
      four groups in relation to intensity and duration of the spawning season: 1)
      limited to one annual spawning, 2) two or more defined spawning periods, 3) two
      or more extended spawning periods, and 4) continuous low intensity spawning. And
      three groups in relation to gonad recovery, and duration and intensity of
      gametogenesis: 1) post spawn and rest stages absent or restricted, 2) fast
      gametogenesis and a clear mature stage. and 3) extended gametogenesis and limited
      maturity stages. The population parameters were classified in relation to age
      structure and number of cohorts, intensity and duration of recruitment, and
      growth rates as expressed by infinity and K. In relation to their life cycle four
      types were found: 1) population represented by only one cohort, at least during
      part of the year, 2) with two or more cohorts at any time, 3) longevity under
      five years, and 4) longevity over live years. In relation to recruitment: 1) one
      recruitment period restricted to a short season, 2) two or more recruitment
      periods, 3) constant recruitment with one or more peaks, and 4) constant
      recruitment without periods of dominance.

PMID- 15264561
TI  - [Gonadic cycle of the American oyster Crassostrea virginica (Lamellibranchia:
      Ostreidae) in Mecoacan, Tabasco, Mexico].
AB  - The American oyster Crassostrea virginica is exploited along Gulf of Mexico. This
      resource represents a job source and incomes for fishermen. In Mexico the
      production is supported by Tabasco state, the first producer. However, the
      mexican landings of this bivalve had been dropped about 40% last ten years. By
      1999, Tabasco presents a unique ban season fishery of oysters. This season was
      based in evaluation of gonadal development by visual observations of color and
      texture, larvae and seeds abundance. In 2000, the government set up two ban
      seasons in terms of evaluation of populations every year, without gonadal
      analysis. In general, exists different spawning seasons for American oyster, in
      accordance with the environmental conditions. It is necessary to establish a ban
      season according to reproductive cycle. This study presents the gonadic cycle for
      an oyster population of Mecoacin lagoon along a year. It was defined five phases
      of the gonad development: resting, gametogenesis, mature or ripe, spawn and post
      spawn. Gametogenesis is present all the year, except December. The spawning
      activity was detected all year, except July and August. The ripe phase presented
      maximum values in August and December. It was proposed a modification of the ban
      seasons from April 15 - May 30, and September 15 - October 30 to March 15 - May
      15 and September 1 - October 30, respectively, according to gonadic cycle
      obtained in this work. This modification would to avoid capture mature organisms
      (ready to spawn).

PMID- 15264562
TI  - [Reproductive activity of Strombus gigas (Mesogasteropoda: Strombidae) in
      differente habitats of Alacranes reef, Yucatan].
AB  - The spawning relationships with temperature/photoperiod of Strombus gigas were
      investigated considering three habitats in Alacranes Reef, Yucatan, between
      February 1999 and March 2000. The sites were 22 degrees 34'N, 89 degrees 42'W
      (site 1); 22 degrees 29'N, 89"45'W (site 2) and 22 degrees 22'N, 89 degrees 39'W
      (site 3). At each site, transects (100 m x 10 m) were done. Different kinds of
      reproductive behavior of S. gigas was observed: such as copulating and egg
      laying. Individuals alone and egg masses were registered as well. The S. gigas
      shell length and lip thickness were measured. High density of adults was found at
      site 2 with 87 conchs in one transect of 1000 m2. The mean density per m2 was
      0.004 for site 1; 0.035 for site 2; and 0.003 for site 3. The mean shell length
      was 220 mm and the lip thickness mean was 16 mm (N = 783) for all sites. In
      February 1999 egg-laying female was found on sand. There was a high reproductive
      activity at site 2 with 8 egg-laying and 18 egg masses. Minimum reproductive
      activity was found at site 3 with 2 egg masses. The bottom-water temperature was
      related positively with copulating pairs (r = 0.723, f = 11.05, p < 0.01) and egg
      masses (r = 0.736, f = 11.82, p < 0.1). Correlation between photoperiod with
      copulating pairs (r = 0.857, f = 27.78, p < 0.01) and egg masses (r = 0.782, f =
      15.77, p < 0.01) were found as well.

PMID- 15264563
TI  - Detection of gaps in the spatial coverage of coral reef monitoring projects in
      the US Caribbean and Gulf of Mexico.
AB  - As part of the US Coral Reef Task Force's National Program to Map, Assess,
      Inventory, and Monitor US Coral Reef Ecosystems, a comprehensive survey of
      projects/programs monitoring coral reef ecosystems and related habitats (i.e.,
      seagrass beds and mangroves) in the US Caribbean and Pacific was undertaken.
      Information was gathered on a total of 296 monitoring and assessment projects
      conducted since 1990 in the US Caribbean and the Gulf of Mexico. Substantial gaps
      in monitoring coverage of US coral reef ecosystems were revealed through
      geographic information system (GIS) analysis of survey metadata. Although
      southern Florida contains approximately two-thirds of all marine monitoring
      projects found in the US Caribbean and Gulf of Mexico, we were unable to identify
      any ongoing projects that monitor coral reefs along Florida's western coast and
      off of the Florida Middle Grounds. Additionally, Florida is covered by
      approximately 1 900 km2 of mangroves, yet there were only four ongoing projects
      that monitor this ecosystem, leaving gaps in coverage in the Lower and Middle
      Keys and along the eastern and western coasts. The Flower Garden Banks National
      Marine Sanctuary, located offshore of the Texas/Louisiana border, has an integral
      long-term monitoring program, but lacks a monitoring project that gathers long
      term, quantitative data on reef lish abundance and certain water quality
      parameters. Numerous coral reef monitoring projects in Puerto Rico are
      concentrated on the island's southwestern coast surrounding La Parguera, while
      far fewer monitoring projects are conducted along the northern and southeastern
      coasts and around Vieques Island. In the US Virgin Islands, the paucity of
      monitoring projects in large areas of St. Croix and St. Thomas contrasts with
      monitoring activity in three marine protected areas (MPAs), where 66% of the US
      Virgin Islands' coral reef monitoring sites were found. Only a series of
      assessments have been conducted at Navassa, a small, uninhabited island located
      55 km west of Haiti and 137 km northeast of Jamaica. In order to better
      understand changes in coral reef communities and to produce a series of biennial
      reports on the status of US coral reef ecosystems, the National Oceanic and
      Atmospheric Administration (NOAA) is developing a national coral reef monitoring
      network. This network has already begun to fill some of these gaps in monitoring
      coverage through issuing cooperative grants to states and territories to build
      long-term monitoring capacity.

PMID- 15264564
TI  - [Organic extracts with antimicrobian activity from Penicillium sp. (Moniliales)
      isolated from the sponge Ircinia felix (Porifera: Demospongiae)].
AB  - This research expresses the potential of the bacterial activity present in the
      organic extracts obtained from Penicillium sp., isolated from the esponge
      Irciniafelix. This activity was evaluated through agar diffusion test and Minimal
      Inhibitory Concentration (MIC). The susceptibility trials of organic fractions
      were carried out against Staphylococcus aureus, S. epidermidis, Bacillus cereus
      and B. subtilis. The use of the chromatographic techniques (CLV and TLC),
      permitted to obtain bioactive organic extracts of different polarities, of which
      only the EtOAc and MeOH fractions inhibited the growth of the bacteria used. Of
      the EtOAc fractionation, only fraction number 3 EtOAc/Hex presented greatest
      activity against the Gram-positive bacteria. Number 1 EtOAc/Hex fraction
      increased its activity against S. aureus (24 mm) and S. epidermidis (25 mm),
      which can be explained by the loss of possible antagonistic effect during the
      fractionation process. The CMI trials were carried out for the EtOAc number I
      subfraction against S. aureus, S. epidermidis, B. cereus and B. subtilis, wich
      was clinical interest, and shows the potential of this organic extract as
      antimicrobial agent.

PMID- 15264565
TI  - [A case of malformation in Pachycheles serratus (Decapoda: Porcellanidae)].
AB  - An adult male of Pachycheles serratus with a malformation on the right cheliped
      was found during a collection of anomuran crabs in coastal waters of the
      peninsula de Macanao, Margarita island, Venezuela. The specimen was found at La
      Carmela beach (11 degrees 04'N-64 degrees 20'W), and featured a bifurcated fixed
      finger on the right cheliped.

PMID- 15264566
TI  - Influence of salinity on the physiological conditions in mussels, Perna perna and
      Perna viridis (Bivalvia: Mytilidae).
AB  - Perna genus was introduced to Venezuela, but nowadays, Perna perna and Perna
      viridis coexist and are commercially exploited from their natural beds. The aim
      of this work was to determine the effect of salinity on the physiological
      conditions of these species by studying RNA/DNA and Protein/DNA ratios. The
      organisms were collected from natural beds at La Esmeralda, Sucre State,
      Venezuela, and acclimatized for 15 days under laboratory conditions at 25 degrees
      C, 36 per thousand salinity, pH between 7 and 8 and more than 90% of oxygen
      saturation. Later, they were divided in two groups: for one group, the salinity
      concentration was increased (36 to 45 per thousand), and for the other, the
      salinity was decreased (36 to 15 per thousand). The rate of change was 1 per
      thousand every day. Ten organisms per group of both species were taken at each of
      15, 20, 25, 30, 36, 40 y 45 per thousand salinity concentrations. Protein
      (colorimetric method) and nucleic acids (RNA and DNA by fluorometric method)
      concentrations were measured in the digestive gland, gills and adductor muscle
      tissues. Results indicate that P. perna can physiologically compensate the
      increase in salinity, but not when the salinity decreased, when proteins are the
      most needed macromolecules. The Protein/DNA index is directly related to salinity
      changes in both cases. P. viridis shows physiological compensation to salinity
      increases and decreases. The RNA/DNA index value in both cases supports this.
      Digestive gland and muscle tissues are the regulating tissues in both species.
      These results show that P. viridis has a higher degree of adaptability to
      salinity changes and, therefore, a greater potential for aquaculture than P.
      perna.

PMID- 15264567
TI  - [New additions to the marine algae of Mochima National Park, Sucre, Venezuela].
AB  - The marine algal flora from the eastern coast of Mochima National Park, Sucre,
      Venezuela was studied with a total of 51 taxa identified, including eight new
      additions of red algae which are Erythrotrichia carnea (Dillwyn) J. Agardh,
      Sahlingia subintegra (Rosenvinge) Kornmann, Liagora ceranoides Lamouroux,
      Asparagopsis taxiformis (Delile) Trevisan, Dasya corymbifera J. Agardh, Chondria
      dasyphylla (Woodward) C. Agardh, Herposiphonia secunda f. tenella (C. Agardh)
      M.J. Wynne and Polysiphonia subtilissima Montagne. Morphological and anatomical
      aspects of the specimens are described and illustrated.

PMID- 15264568
TI  - [Disease in scleractinian corals: a new problem in the reef at Cayo Sombrero,
      Morrocoy National Park, Venezuela?].
AB  - At the beginning of 1996 coral reefs in Morrocoy National Park, Venezuela,
      suffered an unprecedented mass mortality event. As a consequence, live coral
      cover dropped to 2-10%. One of the few reefs that kept live coral cover over 35%
      was Cayo Sombrero; nonetheless, the presence of some coral diseases has been
      detected within the past 2 years, representing a new source of coral mortality.
      Due to this situation, this study started a monitoring program on the incidence
      of coral diseases and syndromes in the reef of Cayo Sombrero. The CARICOMP
      protocol was used in order to evaluate reef health. Ten parallel band-transects
      (20 x 2m) where established at two depth intervals: Five between 3-8 m and five
      between 8-12 m, and the frequency of both, healthy and unhealthy colonies of each
      coral species was recorded along each band transect. In addition to other sources
      of coral damage (predation, siltation, etc), significant differences in disease
      incidence between the two depths intervals were tested with a Kruskall-Wallis
      test. The main problems observed were coral diseases such as yellow band (4.2%),
      dark spots (1.61%) and white plague-II (1.4%), mainly affecting Montastraea
      faveolata, M. annularis and Siderastrea siderea. Siltation, affecting massive
      colonies, such as Colpophyllia natans and Diploria strigosa; algae overgrowth,
      predation, anchor damage, and bleaching. Significant differences were found in
      the incidence of unhealthy (Kruskall-Wallis, p < 0.05) bleached (Kruskall-Wallis,
      p < 0.05) and colonies affected by siltation (Kruskall-Wallis, p < 0.05). More
      than 60% of the 585 coral colonies surveyed at both depths were found to be
      healthy, indicating that the Cayo Sombrero reef is still in good conditions
      compared to other localities in the Park. This study stresses the need to conduct
      early monitoring programs that survey coral disease incidence as a source of
      mortality for this coral reef.

PMID- 15264569
TI  - [Present state of diseases and other signs of reef deterioration at seven coral
      reefs at Los Roques Archipelago National Park, Venezuela].
AB  - This work was aimed to determine the incidence of coral diseases in six different
      reef sites at the Parque Nacional Archipielago de Los Roques, Venezuela: Arrecife
      de herradura, Arrecife costanero, both at Dos Mosquises Sur Key, Boca de Cote,
      Carenero, Crasqui and Pelona de Rabusqui. Each reef was surveyed by using ten 10
      m2-band transects (10 x 1 m), placed parallel to the long axis of the reef within
      a depth gradient ranging from 1 to 9 m depth. All healthy and injured corals,
      along each band transect, were counted and identified to species level.
      Additionally, all diseases and recent mortality that were still identifiable on
      each colony were also recorded. The occurrence of diseased colonies and other
      signs of reef decline between localities were compared by means of a Chi2 test.
      The absolute, relative and mean incidence was estimated for each disease and
      other signs of damage observed for all coral species surveyed at each site. The
      overall incidence of coral diseases was low for all the localities surveyed, only
      6.04% of the 3 344 colonies observed, showed signs of diseases. The most
      important diseases recorded were the Yellow-Blotch Disease (YBD) and Dark Spots
      Disease (DSD) with 2.1% +/- 1.52 y 2.1% +/- 2.54, respectively. Significant
      differences were found in the incidence of coral diseases between reef sites
      (Chi2 p < 0.05). Finally, the occurrence of colonies injured by parrotfish bites
      and pomacentrids was higher compared with the incidence of coral diseases for all
      the reefs surveyed. In conclusion, currently the proportion of healthy colonies
      at Los Roques coral reefs is higher than the percentage of both diseased and
      injured colonies.

PMID- 15264570
TI  - Variation in subsurface seawater temperature off Discovery Bay, Jamaica and the
      U.S. Virgin Islands.
AB  - Long-term, high accuracy seawater temperature data sets are essential in studies
      assessing environmental changes that may alter coral reef communities. Located at
      the approximately the same latitude, the subsurface seawater temperature (S3T)
      off Discovery Bay, Jamaica (DBJ) and the U.S. Virgin Islands (USVI) had the same
      overall mean temperature. The USVI S3T during the winter months is approximately
      0.5 degrees C warmer than DBJ, while May - July at DBJ is approximately 1 degrees
      C warmer than USVI S3T. With the passing of tropical storms in 1995 and 1997 in
      the USVI S3T dropped as much as 1.5 degrees C within a 20 hr period and did not
      revert to the previous temperature during that calendar year. Mean monthly S3T
      during 2000 and 2001 in the USVI was > 0.5 degrees C warmer than during similar
      periods in the early 1990s. Mean monthly S3T during 1999-2002 at DBJ was 0.27
      degrees C cooler than during 1994-1995.

PMID- 15264571
TI  - [Evaluation of the impact of recreational dive activity on the community
      structure of some coral reefs at Los Roques Archipelago National Park, Venezula].
AB  - In order to evaluate if snorkeling had significant effects on coral community
      structure, three different coral reefs (Madrizqui, Pelona de Rabusqui and
      Crasqui) located at Archipelago Los Roques National Park, Venezuela, were
      surveyed. For each site, the coral community structure of two different areas,
      one subjected to intense snorkeling use (FB) and other not frequently used (PFB),
      were compared. Community structure was determined with 1 m2-quadrants and 20 m
      long transects. These communities were described in terms of species richness,
      diversity (Shannon-Wiener) and evenness indexes, live and dead coral cover and
      cover of other organisms (sponges, octocorals and algae). Comparisons within
      sites were performed with a Kruskall-Wallis test. A total of 24 species of
      scleractinian corals were found. Live coral cover ranged from 29.9% +/- 26.43
      (Crasqui) to 34.55% +/- 6.43 (Madrizqui), while dead coral cover ranged from
      32.51% +/- 2.86 (Madrizqui) to 60.78% +/- 21.3 (Pelona de Rabusqui). The PFB
      areas showed higher live coral cover compared to FB areas; however, significant
      differences were only found in Crasqui and Pelona de Rabusqui (p < 0.05). Species
      richness, diversity and evenness were variable and no trends were observed
      between FB and PFB areas. The frequency of both damaged and diseased colonies
      were low (< 1%), most damages observed were natural (parrotfish predation).
      Damages caused by divers such as fin impacts, were not found at the reefs
      studied. These results suggest that, currently, diving pressure is not as high to
      cause massive loses of live coral cover in these reefs. However, the lack of
      strict controls for these activities might produce long-term changes in the
      structure of these coral communities.

PMID- 15264572
TI  - [Community structure of fishes on the east coast of the island of Cabagua,
      Venezuela].
AB  - The community structure of fishes on a sandy beach with patch of Thalassia and
      coral reefs was studied at Punta Las Cabeceras, Cubagua Island, Venezuela.
      Diurnal monthly samples were obtained from March 1999 to February 2000. Numerical
      abundance of fish species was recorded to determine the specific diversity. A
      total of 1 268 individual from 38 species and 20 families were identified:
      Haemulidae, Scaridae and Gerreidae were the more abundant, with 7, 4 and 3
      species, respectively. Nicholsina usta, Eucinostomus argenteus, Halichoeres
      bivittatus and Tylosurus crocodiles made up 74.38% of the abundance, and present
      in 50% of the samples. The number of species occasional visitors was 30 (78.94%),
      indicative of the mobilization from another areas. On a monthly basis, the
      species number varied between 2 and 12; diversity index between 0.98 and 2.93
      bits ind(-1), equitability (J') from 0.44 to 0.98, both indices showing the same
      tendency. N. usta and E. argenteus had the highest biological index equivalent to
      59.1 and 60.0%, respectably, of the maximum possible total and were dominants and
      characteristics fishes of the community.

PMID- 15264573
TI  - Identification of carbohydrate degrading bacteria in sub-tropical regions.
AB  - Several bacteria from the islands of Puerto Rico, Vieques and Trinidad were
      isolated for their carbohydrate degrading activities. These terrestrial and
      marine bacterium were collected from pineapple agricultural lands, tropical rain
      forests, coastlands and mangrove swamps. Organisms were screened for activity
      using chromogenic substrates (AZCL Megazyme International Ltd., Ireland). The
      media composition for the effective culturing of some of the marine organisms has
      also been standardized. Gram-negative organisms were identified by sequence
      analysis of the PCR- amplified partial small subunit rRNA gene. Results indicate
      that the majority of the marine organisms tested belong to the genera Vibrio and
      Pseudoalteromonas and in the terrestrial environments Chryseobacterium
      predominated. These experiments reveal that sub-tropical environments are
      potentially good sources of microorganisms with novel carbohydrase activities.

PMID- 15264574
TI  - [Hypoglycaemic coma, a feared paroxysmal phenomenon in type 1 diabetic patient].
AB  - The hypoglycaemic coma is a severe complication for type 1 diabetic patients.
      Rarely fatal it may be associated with various paroxysmal accidents, potentially
      harmful, especially during driving. Hypoglycaemia certainly alters the quality of
      life because it markedly increases the anxiety of both the patient and his/her
      family. It is considered as a major limiting factor in the glycaemic management
      of type 1 diabetic patients. Being the consequence of numerous causal factors,
      hypoglycaemic coma is not always easy to prevent and may occur as a paroxysmal
      phenomenon, sometimes without obvious contributing circumstances. After having
      defined the various hypoglycaemic thresholds, we will analyse the pathophysiology
      of insulin-induced hypoglycaemia and of its hormonal counterregulation, and we
      will describe the hypoglycaemia unawareness phenomenon. These elements should
      help to better understand why a hypoglycaemic coma may suddenly occur in a
      diabetic patient. Some advices will also be given to reduce the risk of such a
      paroxysmal complication in patients with type 1 diabetes.

PMID- 15264575
TI  - [Porphyrias, a rare cause of acute abdominal pain].
AB  - The porphyrias are uncommon disorders caused by deficiencies of some enzymes of
      the heme biosynthetic pathway. Only four hepatic porphyrias are able to cause
      acute abdominal syndrome. In any case, the diagnosis requires the demonstration
      of increased urinary or stool excretion of accumulated metabolites of heme
      synthesis. Treatment is now possible and is able to reduce the burden of these
      metabolic diseases. The management implies also the identification of trigger
      exogenous factors such as oral contraceptives.

PMID- 15264576
TI  - [Gout].
AB  - In the presence of a clinical acute monoarthritis, a differential diagnosis has
      to be made between septic arthritis, gout and diffuse chondrocalcinosis. Gout
      comes from a purine nucleotide metabolism disorder leading to serum urate level
      elevation. This hyperuricemia can lead to the deposition of monosodium urate
      crystals in the joints, causing acute attacks. After long-term evolution, others
      tissues as the kidneys can be involved: it is chronic gout. The definite
      diagnosis is based on the presence of monosodium urate crystals in the joint
      fluid. The diagnosis of gout should prompt a search for associated medical
      conditions that may affect both urate levels and longevity. These include
      alcoholism, various nephropathies, myeloproliferative disorders, and
      hypertension.

PMID- 15264577
TI  - [Transient ischemic attacks: a new definition].
AB  - According to its initial definition, which dates back more than 50 years, a
      transient ischemic attack (TIA) is a sudden focal neurologic deficit lasting for
      less than 24 hours, of presumed vascular origin, and confined to an area of the
      brain or eye perfused by a specific artery. Recent data on the pathophysiology of
      cerebral ischemia and the progress made by the imaging techniques have led an
      American TIA Working Group to propose a new definition which states that: "A
      transient ischemic attack is a brief episode of neurologic dysfunction, caused by
      local brain or retinal ischemia, with clinical symptoms typically lasting less
      than one hour, and without evidence of cerebral infarction". The advantages and
      limitations of this new definition, the need for an emergency medical care in the
      presence of a TIA, the clinical signs associated with this condition, the
      diagnostic work up, and the differential diagnosis are briefly discussed. A
      clinical example illustrates the difficulties that can be encountered in a case
      of TIA.

PMID- 15264579
TI  - [Panic attack].
AB  - Panic attacks can occur unexpectedly and in almost any situation. The present
      article discusses the main features of anxiety states, the approach, the
      management and the practice guidelines for the treatment of panic disorder.

PMID- 15264578
TI  - [Severe paroxysmal drug eruptions].
AB  - Some drug reactions showing cutaneous expression exhibit a paroxysmal course.
      These diseases encompass the toxic epidermal necrolysis, the drug
      hypersensitivity syndrome, and the acute generalized exanthematic pustulosis.
      These syndromes are associated with dismal outcome. They represent medical
      emergencies needing hospitalization in specialized care units.

PMID- 15264580
TI  - [Paroxysmal atrial fibrillation].
AB  - Paroxysmal atrial fibrillation is one of the most common disorders of cardiac
      rhythm. It is often a step toward permanent arhythmia, specially if associated
      with cardiac disease. The management objectives of intermittent arhythmia may be
      different, as maintenance of sinus rhythm. However, risks of stroke and thrombo
      embolism are similar to those for sustained atrial fibrillation and must be
      carefully assessed. In this article we review the epidemiology, pathophysiology,
      clinical aspects and current guidelines for treatment and management of
      paroxysmal atrial fibrillation.

PMID- 15264581
TI  - [Paroxysmal supraventricular tachycardia].
AB  - Paroxysmal supraventricular tachycardias are often encountered in young and
      otherwise healthy patients. They are rarely life threatening even though they may
      alter the quality of life. In this article, we review the acute treatment of an
      episod of tachycardia and the prevention of recurrences.

PMID- 15264582
TI  - [Syncope].
AB  - Syncope remains a clinical challenge. Accurate history taking, physical
      examination and EKG are mainstays of the diagnosis work up. The most important
      parameter for prognosis and requiring aggressive management is a structural heart
      disease. Patient without cardiopathy presenting multiple episodes may be
      candidate for tilt testing and loop EKG recorder.

PMID- 15264583
TI  - [Paroxysmal tachyarrhythmias in pediatrics].
AB  - The purpose of this retrospective study was to investigate the clinical
      characteristics in pediatric patients with supraventricular or ventricular
      tachycardia. Sixty-nine pediatric patients were included. Age distribution at
      first episode of tachyarrythmia, most indicative symptoms and signs, associated
      conditions and long-term prognosis were determined for the different mechanisms
      of tachyarrythmia. 78% of the children had supraventricular tachycardia and 22%
      ventricular tachycardia. At diagnosis, 57% of the children with supraventricular
      tachycardia were younger than 1 year. The majority of infants were detected
      during routine investigation without having any complaints whereas the majority
      of children presented with symptoms. Recurrence was rare in cases diagnosed
      during infancy, but was usual in cases diagnosed beyond infancy.

PMID- 15264585
TI  - [Recurrent paroxystic vertigo].
AB  - The author describes the pathology, the symptoms and the treatment of these
      vertigo.

PMID- 15264584
TI  - [Familial Mediterranean fever].
AB  - Familial Mediterranean Fever (FMF) is an hereditary disease that especially
      affects people living around the Mediterranean sea. It is characterized by
      recurring fever and abdominal pain, eventually associated with localised
      pleuritis, synovitis or skin inflammation. The most serious complication is
      amyloidosis, which can lead to terminal renal failure. The attacks and
      complications can be avoided by life long administration of colchicine. Two
      independent French and American teams discovered the gene responsible for the
      disease in 1997. It encodes for a protein named pyrin/marenostrin involved in the
      homeostasis the inflammatory mechanisms. The main mutations have been identified
      and are henceforth accessible for molecular screening.

PMID- 15264586
TI  - [Paroxystic abdominal pain in children].
AB  - Acute abdominal pain in children is a frequent symptom of a wide spectrum of
      abdominal and extra-abdominal pathologies. Some of them are more common in
      specific age groups. Prompt diagnosis and treatment are facilitated by a good
      knowledge of the etiologies. Although surgery is mandatory in most of the cases
      of perforation, torsion, ischemia or necrosis, a medical treatment will prevent
      an unnecessary laparotomy in some circumtances.

PMID- 15264587
TI  - [Peri-anaesthetic anaphylactic shock: myths and facts].
AB  - Peri-anaesthetic anaphylactic shock is a fortunately rare event, which
      nevertheless often turns out to be life-threatening. Only fast recognition and
      reaction can permit to avoid its sometimes dramatic consequences. This implies,
      from the anaesthetist, good knowledge of the mechanisms, of the events'sequence,
      of the usual triggering drugs and, of course, of the anaphylactic shock's
      treatment. After such an accident has occured the patient should be referred to
      an allergy specialist in order to perform a thorough exploration, thus pointing
      out which drug is responsible for the reaction, and by which mechanism. Drugs to
      be banished in the future would so be identified and should be taken to the
      patient's as well as his general practician's knowledge.

PMID- 15264589
TI  - [Cancer genetic counseling as it pertains to gynaecologic oncology: general
      considerations in hereditary tumors].
AB  - One of the most remarkable discoveries during the last two decades is that cancer
      is a genetic disease, which develops in a stepwise fashion including many gene
      mutations. The nature of hereditary tumours has also been elucidated, with
      recognised inherited germline gene mutations predisposing cancer development.
      These are called cancer susceptibility gene mutations and mostly involve tumour
      suppressor genes, occasionally oncogenes, genes of the apoptosis pathway and DNA
      repair. As a result, cancer genetic counselling centres have been established
      with the objectives of identifying persons at high-risk for cancer development.
      In addition, activities of these centres may involve applied genetics, mostly in
      research setting. The major steps in cancer genetic counselling in terms of
      hereditary tumours include: 1. identifying at risk patients, e.g. gene mutation
      carriers, 2. proper counselling with full information regarding the benefits and
      disadvantages of DNA testing, and 3. preventive measures including screening,
      early detection and prophylactic surgery, drug treatment etc. In this review, the
      natural history and clinical characteristics of hereditary tumours are outlined,
      as well as, the major considerations of cancer genetic counselling are discussed.

PMID- 15264588
TI  - [Thyroid dysfunctions in patients with viral hepatitis treated with interferon
      alpha].
AB  - INTRODUCTION: Many studies have explored that thyroid dysfunctions can be induced
      by cytokine therapy. Most observations were collected in connection with the
      treatment of viral hepatitis with interferon-alpha. AIM AND METHODS: Frequency
      and types of thyroid dysfunction developed during and after recombinant
      interferon-alpha treatment were studied in 138 patients with viral hepatitis C or
      B. Therapy lasted 12 months or more, subjects having thyroid dysfunction at the
      start of therapy were excluded from the study. Thyroid parameters (TSH, FT4, FT3
      and anti-TPO) were controlled every third month. In patients in whom thyroid
      dysfunction occurred the measurements were repeated monthly and other tests were
      also performed (anti-Tg, IL-6, TSH receptor antibody, thyroid scan and 99mTc
      pertechnetate uptake). RESULTS: Thyroid function disturbances were found in 30
      (21.7%) patients, 12 of them (8.7%) showed persistent hypothyroidism.
      Hyperthyroidism was transitory in all cases. The clinical course of thyroid
      dysfunction might be monophasic (hyper- or hypothyroidism), biphasic
      (hyperthyroidism followed by hypofunction) or triphasic. Immune and non-immune
      forms can be clearly distinguished. CONCLUSIONS: Every fifth patient with chronic
      hepatitis showed thyroid dysfunction during interferon-alpha therapy, it is
      necessary therefore to control the hormonal status and the thyroid antibody
      titer. Treated patients have to be informed in advance that as a "side effect"
      persistent hypothyroidism may develop.

PMID- 15264590
TI  - [The combined effect of prenatal steroid prophylaxis, neonatal surfactant therapy
      and reduction of risk of complications from respiratory life support on survival
      rate of very low birthweight infants].
AB  - INTRODUCTION: Retrospective analysis on some factors possibly influencing
      survival rate of very low birthweight infants on respiratory life support has
      been carried out. AIM: The aim was to find out about roles played by prenatal
      steroid prophylaxis, neonatal surfactant therapy and methods of reduction of
      complication risk emanating from respiratory life support in the outcome of
      treatment. METHOD: The frequency rate of pneumothorax, pneumomediastinum and
      bronchopulmonary dysplasia was comparatively examined for all very low
      birthweight (less than 1500 g) neonates treated by respiratory life support in
      the I. Department of Obstetrics and Gynecology, Semmelweis University in 1999 (n
      = 178) and in 1989 (n = 78). Corresponding data were compared using t-tests.
      RESULTS: In 100% of the 1999 patients in the focus of the current investigation
      (178 newborn infants) have received prenatal steroid prophylaxis and 55% of them
      (98 neonates) have received neonatal surfactant therapy. Respiratory life support
      resulted in pneumothorax in 7.8% of them (14 patients) and bronchopulmonary
      dysplasia in 12.3% of them (22 neonates). Frequency rate of complications for the
      neonates under investigation attributable to respiratory support or initial
      illness decreased from 38.6% in 1989 to 19.6% in 1999, a difference proven
      significant by t-test (p < 0.05). Survival rate increased from 34.6% in 1989 to
      63.5% in 1999, which is again a significant difference indicated by t-test (p <
      0.05). The differences are especially consequential considering that the average
      gestation age of the infants in the 1999 group was lower than that of the infants
      in the 1989 group. CONCLUSION: Decrease in complication rate emanating from
      respiratory support and increase in survival rate over the 10 year period between
      1989 and 1999 can be attributed to the combined effect of improvement in
      respiratory support therapy applied (aiming to minimise its adverse effects like
      barotrauma and volutrauma more effectively by refined technological means) and of
      the introduction of administering prenatal steroid prophylaxis and (if judged
      necessary) neonatal surfactant therapy. A considerable limitation of this study
      is the lack of separation of independent variables (the separate effects due to
      the separate treatments applied), but it is reasonable to believe that
      improvement was due to a combined effect of all changes in treatments indicated
      above. It is deemed probable that results can be further improved by finding ways
      to decrease barotrauma and volutrauma even more effectively than now.

PMID- 15264591
TI  - [Virtual bronchoscopy for follow-up investigation of main airway stenoses].
AB  - The aim of the study was to compare the utility and effectivity of conventional
      and virtual bronchoscopy in the follow up of patients with main airway stenosis.
      23 patients with trachea or main bronchi stenosis were enrolled in the study. The
      causes of the stenosis were malignant or benign tumor, struma and stent. The
      stenoses were evaluated before and after the different interventions (i.e.
      mechanical dilatation, laser photocoagulation, stent implantation, radiotherapy,
      chemotherapy or surgical resection.) The mean time between the first and second
      endoscopic and virtual bronchoscopic examinations was 140 days. The authors found
      good correlation between bronchofiberoscopy and virtual bronchoscopy findings.
      The data of virtual bronchoscopy were more exact. Based on this study the virtual
      bronchocopy can replace the traditional invasive method to follow-up patients
      with main airway stenosis.

PMID- 15264592
TI  - [Correlation of anthropometric parameters and blood-pressure in elderly people].
AB  - INTRODUCTION: The elderly represent a growing segment of populations in developed
      and also in developing countries. Anthropological measurements offer a cheap and
      easy way method for assessment of health and nutritional status and in prediction
      for mortality. Anthropological parameters and their relation to blood pressure
      were studied in elderlies. METHODS: Two hundred-thirteen elderly people (83 men
      over 65 y and 110 women over 60 y) were involved. The weight, height, waist- and
      hip circumferences were measured and waist: hip ratio, and body mass index (BMI)
      were calculated. Blood pressure was measured by the use of sphygmomanometer.
      Hypertension was diagnosed when systolic blood pressure was >/= 140 and/or
      diastolic >/= 90 mmHg. The SPSS 10 version for Windows was used for statistical
      analysis. RESULTS: According to the BMI, 72% of men and 65% women were considered
      overweight or obese. According to waist circumference 51% of men and 83% of women
      belonged to the high risk group. Under 80 y the mean blood pressure was in the
      pathological range both in the case of men and women. That could be considered as
      a sign of the insufficient efficiency of treatment or bad compliance. By 60% of
      this elderly population hypertension was registered. 75% of people, considered
      overweight or obese according to BMI, showed hypertension. According to the waist
      circumference, in 73% of people in the high risk group hypertension was detected
      versus 6% of persons in the non-risk group. This relation could not be observed
      in women. CONCLUSION: The prevalence of obesity and overweight is higher in the
      elderly group than in the younger adult population. Decrease in body mass may be
      suggested only by cautious nutritional intervention, control of systolic blood
      pressure should be more regular and prudent.

PMID- 15264593
TI  - [Treatment of rhinitis].

PMID- 15264594
TI  - The Swedish Regional Climate Modelling Programme, SWECLIM: a review.
AB  - The Swedish Regional Climate Modelling Programme, SWECLIM, was a 6.5-year
      national research network for regional climate modeling, regional climate change
      projections and hydrological impact assessment and information to a wide range of
      stakeholders. Most of the program activities focussed on the regional climate
      system of Northern Europe. This led to the establishment of an advanced, coupled
      atmosphere-ocean-hydrology regional climate model system, a suite of regional
      climate change projections and progress on relevant data and process studies.
      These were, in turn, used for information and educational purposes, as a starting
      point for impact analyses on different societal sectors and provided
      contributions also to international climate research.

PMID- 15264595
TI  - Recent mild and wet years in relation to long observation records and future
      climate change in Sweden.
AB  - Recent mild and wet years in Sweden were compared with long observation series of
      temperature, precipitation and runoff. Spatial average series for northern and
      southern Sweden were constructed and analyzed for the period 1901-2002.
      Precipitation increased considerably during the period, whereas temperature and
      runoff increases were weaker. On average, for the whole country, the differences
      between the period 1991-2002 and 1901-1990 were +0.7 degrees C for temperature,
      +11% in precipitation and +7% in runoff. The differences in temperature and
      precipitation, but not runoff, were significant at the 5% level. However, the
      1930s were equally mild, and the runoff was almost as high in the 1920s. The
      characteristic feature of the past decade is the combination of high temperature,
      precipitation and runoff. The deviation between the most recent decade and the
      preceding years is consistent with climate scenario projections for Sweden, but
      there are also differences in the seasonal pattern.

PMID- 15264596
TI  - Spatial analysis of extreme precipitation in Sweden 1961-2000.
AB  - Extreme daily precipitation in Sweden for the years 1961-2000 is analyzed with
      respect to spatial scale, regional variations and associated weather types.
      Correlograms based on a lag distance of 30 km estimated the spatial scale of
      variation of the annual mean precipitation, the 99th percentile of daily
      precipitation and the average of annual maximum daily precipitation to 100 km, 60
      100 km and 40-70 km, respectively. Regions of correlation with respect to
      precipitation at 82 stations during days of extreme events are identified through
      Maximum-Likelihood Factor Analysis. Eleven factors are found to provide the
      optimum factor solution. Weather types for the days of extreme events are
      determined by an objective classification scheme, based on daily sea level
      pressure, which is modified by subjective inclusion of fronts. In total, 63% of
      the extreme events occurred during cyclonic weather types, 32% during frontal, 3%
      during directional and 2% during anticyclonic types. The frequency of the weather
      types during extreme events varied between the regions however.

PMID- 15264597
TI  - Recent and future signatures of climate change in Europe.
AB  - A set of six regional climate model experiments is investigated for future
      changes in daily temperature and precipitation in Europe. Changes in the
      probability distributions for these variables are studied. It is found that the
      asymmetry of these distributions change differently depending on location and
      season. Large summertime changes in extremely high temperatures in central,
      eastern and southern Europe are followed by higher than average temperature
      increases on warm days in general. Likewise, temperatures on cold days increase
      much more than the average temperature increase during winter in eastern and
      northern Europe. A comparison with historical data on wintertime temperature
      shows that the model simulated and observed daily variability are similar. In
      particular, the much stronger increase in temperatures on cold days, compared to
      the average temperature increase as observed in warm compared to cold historical
      periods, is simulated also by the model. The contribution from heavy
      precipitation events is simulated to increase over most parts of Europe in all
      seasons.

PMID- 15264598
TI  - The Rossby Centre Regional Atmospheric Climate Model part I: model climatology
      and performance for the present climate over Europe.
AB  - The Rossby Centre Atmospheric Regional Climate Model (RCA2) is described and
      simulation results, for the present climate over Europe, are evaluated against
      available observations. Systematic biases in the models mean climate and climate
      variability are documented and key parameterization weaknesses identified. The
      quality of near-surface parameters is investigated in some detail, particularly
      temperature, precipitation, the surface energy budget and cloud cover. The model
      simulates the recent, observed climate and variability with a high degree of
      realism. Compensating errors in the components of the surface radiation budget
      are highlighted and the fundamental causes of these biases are traced to the
      relevant aspects of the cloud, precipitation and radiation parameterizations. The
      model has a tendency to precipitate too frequently at small rates, this has a
      direct impact on the simulation of cloud-radiation interaction and surface
      temperatures. Great care must be taken in the use of observations to evaluate
      high resolution RCMs, when they are forced by analyzed boundary conditions. This
      is particularly true with respect to precipitation and cloudiness, where
      observational uncertainty is often larger than the RCM bias.

PMID- 15264599
TI  - The Rossby Centre Regional Atmospheric Climate Model part II: application to the
      Arctic climate.
AB  - The Rossby Centre regional climate model (RCA2) has been integrated over the
      Arctic Ocean as part of the international ARCMIP project. Results have been
      compared to observations derived from the SHEBA data set. The standard RCA2 model
      overpredicts cloud cover and downwelling longwave radiation, during the Arctic
      winter. This error was improved by introducing a new cloud parameterization,
      which significantly improves the annual cycle of cloud cover. Compensating biases
      between clear sky downwelling longwave radiation and longwave radiation emitted
      from cloud base were identified. Modifications have been introduced to the model
      radiation scheme that more accurately treat solar radiation interaction with ice
      crystals. This leads to a more realistic representation of cloud-solar radiation
      interaction. The clear sky portion of the model radiation code transmits too much
      solar radiation through the atmosphere, producing a positive bias at the top of
      the frequent boundary layer clouds. A realistic treatment of the temporally
      evolving albedo, of both sea-ice and snow, appears crucial for an accurate
      simulation of the net surface energy budget. Likewise, inclusion of a prognostic
      snow-surface temperature seems necessary, to accurately simulate near-surface
      thermodynamic processes in the Arctic.

PMID- 15264600
TI  - Model simulations of the Arctic atmospheric boundary-layer from the SHEBA year.
AB  - We present Arctic atmospheric boundary-layer modeling with a regional model
      COAMPS, for the Surface Heat Budget of the Arctic Ocean (SHEBA) experiment. Model
      results are compared to soundings, near-surface measurements and forecasts from
      the ECMWF model. The near-surface temperature is often too high in winter, except
      in shorter periods when the boundary layer was cloud-capped and well-mixed due to
      cloud-top cooling. Temperatures are slightly too high also during the summer melt
      season. Effects are too high boundary-layer moisture and formation of too dense
      stratocumulus, generating a too deep well-mixed boundary layer with a cold bias
      at the simulated boundary-layer top. Errors in temperature and therefore moisture
      are responsible for large errors in heat flux, in particular in solar radiation,
      by forming these clouds. We conclude that the main problems lie in the surface
      energy balance and the treatment of the heat conduction through the ice and snow
      and in how low-level clouds are treated.

PMID- 15264601
TI  - Hydrological change--climate change impact simulations for Sweden.
AB  - Climate change resulting from the enhanced greenhouse effect is expected to give
      rise to changes in hydrological systems. This hydrological change, as with the
      change in climate variables, will vary regionally around the globe. Impact
      studies at local and regional scales are needed to assess how different regions
      will be affected. This study focuses on assessment of hydrological impacts of
      climate change over a wide range of Swedish basins. Different methods of
      transferring the signal of climate change from climate models to hydrological
      models were used. Several hydrological model simulations using regional climate
      model scenarios from Swedish Regional Climate Modelling Programme (SWECLIM) are
      presented. A principal conclusion is that subregional impacts to river flow vary
      considerably according to whether a basin is in northern or southern Sweden.
      Furthermore, projected hydrological change is just as dependent on the choice of
      the global climate model used for regional climate model boundary conditions as
      the choice of anthropogenic emissions scenario.

PMID- 15264602
TI  - Climate change effects on river flow to the Baltic Sea.
AB  - River flow to the Baltic Sea originates under a range of different climate
      regimes in a drainage basin covering some 1,600,000 km2. Changes to the climate
      in the Baltic Basin will not only affect the total amount of freshwater flowing
      into the sea, but also the distribution of the origin of these flows. Using
      hydrological modeling, the effects of future climate change on river runoff to
      the Baltic Sea have been analyzed. Four different climate change scenarios from
      the Swedish Regional Climate Modelling Programme (SWECLIM) were used. The
      resulting change to total mean annual river flow to the Baltic Sea ranges from 
      2% to +15% of present-day flow according to the different climate scenarios. The
      magnitude of changes within different subregions of the basin varies
      considerably, with the most severe mean annual changes ranging from -30% to +40%.
      However, common to all of the scenarios evaluated is a general trend of reduced
      river flow from the south of the Baltic Basin together with increased river flow
      from the north.

PMID- 15264603
TI  - Simulated sea surface temperature and heat fluxes in different climates of the
      Baltic Sea.
AB  - The physical state of the Baltic Sea in possible future climates is approached by
      numerical model experiments with a regional coupled ocean-atmosphere model driven
      by different global simulations. Scenarios and recent climate simulations are
      compared to estimate changes. The sea surface is clearly warmer by 2.9 degrees C
      in the ensemble mean. The horizontal pattern of average annual mean warming can
      largely be explained in terms of ice-cover reduction. The transfer of heat from
      the atmosphere to the Baltic Sea shows a changed seasonal cycle: a reduced heat
      loss in fall, increased heat uptake in spring, and reduced heat uptake in summer.
      The interannual variability of surface temperature is generally increased. This
      is associated with a smoothed frequency distribution in northern basins. The
      overall heat budget shows increased solar radiation to the sea surface, which is
      balanced by changes of the other heat flux components.

PMID- 15264604
TI  - Simulated distributions of Baltic Sea-ice in warming climate and consequences for
      the winter habitat of the Baltic ringed seal.
AB  - Sea-ice in the Baltic Sea in present and future climates is investigated. The
      Rossby Centre Regional Atmosphere-Ocean model was used to perform a set of 30
      year-long time slice experiments. For each of the two driving global models
      HadAM3H and ECHAM4/OPYC3, one control run (1961-1990) and two scenario runs (2071
      2100) based upon the SRES A2 and B2 emission scenarios were conducted. The future
      sea-ice volume in the Baltic Sea is reduced by 83% on average. The Bothnian Sea,
      large areas of the Gulf of Finland and Gulf of Riga, and the outer parts of the
      southwestern archipelago of Finland will become ice-free in the mean. The
      presented scenarios are used to study the impact of climate change on the Baltic
      ringed seal (Phoca hispida botnica). Climate change seems to be a major threat to
      all southern populations. The only fairly good winter sea-ice habitat is found to
      be confined to the Bay of Bothnia.

PMID- 15264605
TI  - Baltic sub-basin turnover times examined using the Rossby Centre Ocean model.
AB  - Not least when judging the possible effects of climate change it proves necessary
      to estimate the water-renewal rates of limited marine areas subject to pronounced
      external influences. In connection with the SWECLIM programme this has been
      undertaken for two ecologically sensitive sub-basins of the Baltic, viz. the Gulf
      of Riga and Gdansk Bay. For this purpose two methodologically different
      approaches have been employed, based on mass-balance budgets and analysis of
      Lagrangian trajectories, respectively. When compared to the results obtained
      using the Lagrangian technique, the box-model approach proved to be adequate for
      the Gulf of Riga representing a morphologically highly constrained basin, whereas
      it demonstrated certain shortcomings when applied to the more open topographic
      conditions characterizing Gdansk Bay.

PMID- 15264606
TI  - The Baltic haline conveyor belt or the overturning circulation and mixing in the
      Baltic.
AB  - A study of the water-mass circulation of the Baltic has been undertaken by making
      use of a three dimensional Baltic Sea model simulation. The saline water from the
      North Atlantic is traced through the Danish Sounds into the Baltic where it
      upwells and mixes with the fresh water inflow from the rivers forming a Baltic
      haline conveyor belt. The mixing of the saline water from the Great Belt and
      Oresund with the fresh water is investigated making use of overturning stream
      functions and Lagrangian trajectories. The overturning stream function was
      calculated as a function of four different vertical coordinates (depth, salinity,
      temperature and density) in order to understand the path of the water and where
      it upwells and mixes. Evidence of a fictive depth overturning cell similar to the
      Deacon Cell in the Southern Ocean was found in the Baltic proper corresponding to
      the gyre circulation around Gotland, which vanishes when the overturning stream
      function is projected on density layers. A Lagrangian trajectory study was
      performed to obtain a better view of the circulation and mixing of the saline and
      fresh waters. The residence time of the water masses in the Baltic is calculated
      to be 26-29 years and the Lagrangian dispersion reaches basin saturation after 5
      years.

PMID- 15264607
TI  - A new method for monitoring long-term transport variability in the Baltic.
AB  - Direct measurements of the potential induced by motion of electrically conducting
      seawater through the earth's magnetic field may be used to estimate ocean
      transports. For the purpose of evaluating the feasibility of monitoring the
      Baltic climate, a number of temporary observational systems based on this
      principle have been established around the Swedish coast. Some results from these
      investigations are presented, and the study is concluded by an outlook towards
      the prospects for future work along these lines.

PMID- 15264608
TI  - Nondaily hormonal contraception: considerations in contraceptive choice and
      patient counseling.
AB  - PURPOSE: To review currently available choices for non-daily hormonal
      contraception, considering efficacy, safety, patient counseling issues, and
      appropriate patient selection. DATA SOURCES: Worldwide medical literature and the
      individual products' prescribing information. CONCLUSIONS: Patients and
      clinicians have many nondaily hormonal contraceptive options available--from Depo
      Provera quarterly injection, which has been available in the United States for
      over 10 years, to several new entries (Mirena 5-year intrauterine system, Lunelle
      monthly injection, NuvaRing monthly intravaginal ring, and Ortho Evra weekly
      transdermal patch). All these options offer high efficacy and enhanced
      convenience for many patients over daily oral contraceptives (OCs). Barriers to
      use of these agents may include patients' lack of information as well as fear or
      misconceptions regarding the hormones and methods. All of these can be addressed
      with adequate patient counseling and open dialogue. The clinician and patient
      need to be well-informed regarding these options so that they can work together
      and identify the best contraceptive fit for the patient---with the ultimate goal
      being to increase patient satisfaction and adherence and, thus, avoid unintended
      pregnancy. IMPLICATIONS FOR PRACTICE: Despite the efficacy of OCs, missed pills
      are quite common and contribute to unintended pregnancy. Many women in all
      population categories would benefit from the convenience and reliability of
      nondaily hormonal contraceptives. The highest efficacy rates with typical use are
      associated with agents that require minimal user participation (i.e., Depo
      Provera, Mirena). Compared to daily regimens, all nondaily options offer
      increased convenience and may contribute to improved patient adherence. However,
      barriers to use may exist. Patient fears regarding use of hormones can be
      minimized by discussing the long-term safety of hormonal contraceptives. (The
      data are predominantly derived from Depo-Provera and OCs because these agents
      have been available in the United States and in the rest of the world for much
      longer than the newer nondaily options.) Patient counseling and appropriate
      expectations regarding changes in menstrual pattern have been demonstrated to
      further enhance patient adherence to therapy. Finally, patient lifestyle
      preferences must be considered. The finding that many women are comfortable with
      or even prefer amenorrhea, which is associated with options such as Depo-Provera,
      highlights how important it is for clinicians to avoid making assumptions about a
      patient's contraceptive preferences. Rather, clinicians and patients should
      exchange information through an open dialogue. For the majority of patients,
      nondaily hormonal contraceptives should be considered and offered as first-line
      options.

PMID- 15264609
TI  - Identifying the drug seeker: the advanced practice nurse's role in managing
      prescription drug abuse.
AB  - PURPOSE: To provide advanced practice nurses (APNs) with a definition of drug
      seeking behaviors, to identify the common signs and symptoms of drug-seeking
      behaviors, to furnish tips for managing interactions with and treatment of the
      drug-seeking patient, and to describe prescription parameters that will help APNs
      avoid legal ramifications. DATA SOURCES: A review of the current scientific and
      clinical literature regarding interaction with and treatment of patients who
      abuse prescription drugs. CONCLUSIONS: A basic understanding of drug-seeking
      behaviors and adherence to appropriate procedures for prescribing controlled
      medications are essential for APNs to maintain their safe prescribing habits;
      carry on with quality, effective care; and continue the advancement of their
      profession. IMPLICATIONS FOR PRACTICE: As primary care providers, APNs must be
      aware of the potential complications resulting from interacting with patients who
      may be seeking prescription drugs for recreational or illicit use, rather than
      for legitimate reasons.

PMID- 15264610
TI  - Down syndrome with an unusual etiology: case report and review.
AB  - PURPOSE: To present the genetic etiology of an unusual case of Down syndrome,
      arising from translocation of chromosome 21 to chromosome 9; to discuss advanced
      genetic diagnostic techniques, focusing on how pinpointing a specific genetic
      mistake can influence treatment and outcome; and to review the role of the nurse
      practitioner (NP) in caring for families of children with Down syndrome. DATA
      SOURCES: Case report, literature review, and advanced genetic techniques.
      CONCLUSIONS: NPs often answer patient questions regarding genetic abnormalities
      and risk factors for transmission of genetic errors to offspring. Advanced
      genetic analysis allows for the diagnosis of unusual causes of common genetic
      disorders. The ability to identify a specific genetic mistake and to predict the
      scope of its effect on an individual offers health care providers the opportunity
      to develop a case-by-case plan of care. IMPLICATIONS FOR PRACTICE: NPs have a
      responsibility to be informed about the processes involved in the transmission of
      genetic errors and about the subtleties of various expressions of a genetic
      disorder. The availability of new genetic-testing techniques allows NPs to
      individualize patient care and family teaching.

PMID- 15264611
TI  - Evidenced-based use of botanicals, minerals, and vitamins in the prophylactic
      treatment of migraines.
AB  - PURPOSE: To analyze evidence-based information about alternative prophylactic
      pharmacological migraine treatments utilizing feverfew, butter-bur, magnesium,
      and riboflavin and to discuss the mechanism of action, dosage recommendations,
      side effects, and contraindications for each treatment. DATA SOURCES: Data
      obtained via electronic databases and professional medical references.
      CONCLUSIONS: Current clinical data support the use of fever-few, butterbur,
      magnesium, and riboflavin in migraine prophylaxis; however, studies are limited
      but promising regarding the participants' perceived relief. Studies with rigorous
      methodologies and larger sample sizes are needed to further support the safe and
      effective use of these treatments. IMPLICATIONS FOR PRACTICE: With increased
      patient access to information regarding alternative migraine treatments, nurse
      practitioners (NPs) and other health care providers must be knowledgeable about
      evidence-based data regarding these alternative treatments to appropriately offer
      safe patient care.

PMID- 15264612
TI  - Perceived stress reported by nurse practitioner students.
AB  - PURPOSE: To explore the phenomenon of stress as perceived by nurse practitioner
      (NP) students enrolled in a master of science in nursing program. DATA SOURCES:
      The study utilized a qualitative approach for data collection and analysis
      consistent with grounded theory methodology. We recruited 12 students, 4 men and
      8 women, during their final year of a university-based NP program. Data were
      collected through individual interviews and a demographic questionnaire.
      CONCLUSIONS: Students reported stress levels ranging from moderate to highest
      ever in their lives. Although reasons given for becoming an NP included increased
      autonomy and increased ability, high-level stress was attributed to high demands
      and to independent teaching-learning techniques in the NP courses. Participants
      also expressed concerns about time management and financial obligations.
      IMPLICATIONS FOR PRACTICE: Knowledge of NP students' perceptions regarding
      personal stress can provide insight useful for developing approaches to foster
      optimum learning. Practicing stress reduction techniques with students would not
      only facilitate their own stress reduction but would also reinforce their ability
      to assist clients with this need.

PMID- 15264613
TI  - What is the nature of nurse practitioners' lived experiences interacting with
      patients?
AB  - PURPOSE: To illuminate the nature of the lived experiences of nurse practitioners
      (NPs) interacting with patients, to discover the essential meanings of those
      lived experiences, and to articulate a structure gleaned from the essential
      meanings. DATA SOURCES: Six NPs provided concrete descriptions of their
      experiences interacting with patients. Data were collected and analyzed using a
      descriptive, phenomenological method of inquiry. CONCLUSIONS: The data revealed
      eight essential meanings for interacting with patients: openness, connection,
      concern, respect, reciprocity, competence, time, and professional identity. The
      nature of NPs' lived experiences interacting with patients is an authentic
      attending to health-related concerns, originating and enduring within the context
      of an intersubjective relationship. Through the dialogues that evolve within the
      context of intersubjective relationships, both NPs and patients become more as
      persons, amenable to understanding the meanings each has assigned to his or her
      life-world situations, regardless of the outcomes of any health-related
      interventions. IMPLICATIONS FOR PRACTICE: The NPs in this study valued the
      relationships that ensued from their interactions with patients. From these
      relationships they derived both personal and professional growth. Intersubjective
      relating is the "art of nursing" for the participants in this study.

PMID- 15264614
TI  - Molecular evidence for synonymy of Anopheles yatsushiroensis and An. pullus.
AB  - Identification of species members of the Hyrcanus Group of Anopheles is difficult
      because of intraspecific variation in and interspecific similarity among key
      characters. Hibernating female Anopheles pullus were collected and 6 adults were
      individually reared. All F1 progeny of wild-caught An. pullus were
      morphologically identical to An. yatsushiroensis. The 5.8S rDNA-ITS2-28S rDNA
      region from each of 3 An. pullus and An. yatsushiroensis (wild-caught females)
      and a portion of the mitochondrial cytochrome oxidase 1 genes from 1 individual
      of the 2 species were sequenced. The same gene regions from an An. sinensis were
      sequenced to determine the degree of interspecific sequence variation within the
      Hyrcanus Group. Consensus sequence of the 5.8S rDNA-ITS2-28S rDNA region from 3
      individual An. pullus was completely identical to that from 3 individual An.
      yatsushiroensis. Examination of molecular data obtained from nuclear DNA and
      mitochondrial DNA as well as morphological observations in rearing experiments
      support synonymy of An. yatsushiroensis and An. pullus in Korea.

PMID- 15264615
TI  - Distribution of Ochlerotatus togoi along the Pacific coast of Washington.
AB  - Before this study, the mosquito Ochlerotatus (Finlaya) togoi (Theobald) had been
      reported from only 2 locations within the continental United States, both of
      which were documented in Washington State. This study used active and passive
      surveillance to determine the current distribution of Oc. togoi along the Pacific
      Coast of Washington. Results of the study show that small, but stable,
      populations of Oc. togoi exist in the northern San Juan Island region of Puget
      Sound. Geological formations in this region are conducive to rock holes and
      support populations of Oc. togoi. No members of Oc. togoi were found on the
      southwestern Washington coast, the coast of the Olympic Peninsula, or in the
      lower Puget Sound.

PMID- 15264616
TI  - Studies of the genus Culex in Florida II. Redescription of the fourth instar of
      Culex nigripalpus.
AB  - The fourth instar of Culex nigripalpus is described in detail and completely
      illustrated for the 1st time as compared with previous descriptions of the larva
      of Cx. nigripalpus. Certain important features are shown in the figure.

PMID- 15264617
TI  - Verrallina (Neomacleaya) assamensis, a new species from Assam, India.
AB  - The adult female, adult male, pupa, and larva of Verrallina (Neomacleaya)
      assamensis, a new mosquito species, are described from the Dibrugarh District of
      Assam State, India.

PMID- 15264618
TI  - Insemination rates of hybrids between Culex pipiens pipiens and Culex pipiens
      quinquefasciatus or Culex pipiens pallens at high temperature.
AB  - Females of Culex pipiens pallens are rarely inseminated at temperatures above 30
      degrees C. Insemination and egg-hatching rates (F2) were examined in females of
      hybrids (F1) between Culex pipiens pipiens and Culex pipiens quinquefasciatus at
      25 degrees C and 30 degrees C to examine temperature-dependent reproductive
      activity. Insemination rates were very high in hybrid females (F1) at 25 degrees
      C and 30 degrees C, and egg-hatching rate (F2) also was high at both
      temperatures. Crosses between Cx. p. pipiens and Cx. p. quinquefasciatus did not
      show insemination rates and egg-hatching rates similar to the rates observed in
      Cx. p. pallens, suggesting that the hybrids expressed reproductive activity
      characteristic of Cx. p. quinquefasciatus.

PMID- 15264619
TI  - Distribution and seasonal abundance of Cnephia pecuarum (Diptera: Simuliidae) in
      Arkansas.
AB  - Studies were conducted during 1990-92 to determine the distribution and abundance
      of the southern buffalo gnat (Cnephia pecuarum) in Arkansas. Field collection of
      adults near streams throughout Arkansas demonstrated adult occurrence in 24
      counties. Abundance studies were conducted by using tent traps baited with dry
      ice in 3 counties in southeastern Arkansas. In 1990, studies were conducted in
      Bayou Meto (Ashley County); Seven Devils Swamp (Drew County); and Crocketts
      Bluff, Bayou Meto, and Little LaGrue Bayou (Arkansas County). During 1991 and
      1992, abundance studies were limited to Arkansas County. Results and previous
      field observations suggest 3 distinct populations in Arkansas (southwestern,
      southeastern, and central). Seasonal occurrence extended from December to April
      but varied by location and year. Abundance studies indicated variation in both
      seasonal occurrence and adult density by year and trap location. Although
      investigations during 1990-91 showed similar seasonal occurrence trends (peaking
      in early March), higher adult densities were noted during 1990. In contrast, peak
      adult density during 1992 occurred in late January. Greatest adult density during
      the course of these investigations was 7,160 gnats/24 h during 1990 at Crocketts
      Bluff (Arkansas County). Results suggest that additional studies are warranted to
      determine the impact of environmental and river factors on seasonal occurrence
      and abundance of this pest.

PMID- 15264620
TI  - Evaluation of 1-octen-3-ol and carbon dioxide as attractants for Phlebotomus
      papatasi (Diptera: Psychodidae) in southern Egypt.
AB  - The effectiveness of 1-octen-3-ol (octenol) as an attractant for collecting
      medically important psychodids has never been reported. This study evaluated the
      effects of carbon dioxide (CO2) and octenol released at 2 rates, individually and
      in combination, as attractants for adult sand flies in a small village in
      southern Egypt. Four sand fly species were collected: Phlebotomus papatasi, P.
      sergenti, Sergentomyia palestinensis, and S. schwetzi. Only P. papatasi was
      collected in numbers sufficient to allow statistical analysis. This study
      reaffirms that CO2 is an effective attractant for female P. papatasi and also
      demonstrates that neither male nor female P. papatasi respond to octenol alone.
      Additionally, no synergistic attractancy for either females or males was observed
      when CO2 and octenol were combined.

PMID- 15264621
TI  - A crab-hole mosquito, Ochlerotatus baisasi, feeding on mudskipper (Gobiidae:
      Oxudercinae) in the Ryukyu Islands, Japan.
AB  - Ochlerotatus baisasi was observed and photographed feeding on a mudskipper
      (Periophthalmus argentilineatus). Origin of blood meals in the stomachs of female
      mosquitoes collected at burrows of land crabs and mud lobsters in the mangrove
      forests of Oura, Okinawa, and Komi, Iriomote (the Ryukyu Islands), was determined
      by enzyme-linked immunosorbent assay to be from a fish source.

PMID- 15264622
TI  - Selected mosquito vectors of West Nile virus: comparison of their ecological
      dynamics in four woodland and marsh habitats in Delaware.
AB  - We compared human landing, CO2-baited light trap, CO2-baited Omni-Fay trap, and
      gravid trap collections of mosquitoes at 4 woodland and marsh sites with varied
      vegetative habitats in Delaware during summer 2001. Landing collections provided
      more consistent, but sometimes smaller, collection numbers than light traps.
      Proportions of parous mosquitoes were also higher in landing than in light trap
      or Omni-Fay collections about 65% of the time. Circadian feeding rhythms were
      observed for 3 suspected vector species selected on the basis of 1999-2000
      laboratory vector competence data and their presence at local habitats. These
      species included Aedes vexans, Culex salinarius, and Cx. pipiens pipiens. Aedes
      vexans fed after dusk, primarily before 2200 h and again around dawn (0600-0700
      h). Both Cx. salinarius and Cx. p. pipiens exhibited peak feeding activity after
      dusk and in predawn periods, as well as extended feeding periods up until
      midnight. Time of feeding is an important factor in evaluating vector-host
      associations and risks of human outbreaks.

PMID- 15264623
TI  - Repellency of aromatic medicinal plant extracts and a steam distillate to Aedes
      aegypti.
AB  - The repellent activity of methanol extracts from 23 aromatic medicinal plant
      species and a steam distillate against female blood-starved Aedes aegypti was
      examined in the laboratory by skin test and compared with that of N,N-diethyl-m
      toluamide (deet). Responses varied according to plant species. At a dose of 0.1
      mg/cm2, the repellency of extracts of Cinnamomum cassia bark (91%), Nardostachys
      chinensis rhizome (81%), Paeonia suffruticosa root bark (80%), and Cinnamomum
      camphora steam distillate (94%) was comparable to deet (82%). The duration of the
      effectiveness for extracts from C. cassia bark and N. chinensis rhizome was
      comparable to deet and lasted for approximately 1 h. Relatively short duration of
      repellency was observed in P. suffruticosa root bark extract and C. camphora
      steam distillate. The plants described merit further study as potential mosquito
      repellent agents.

PMID- 15264624
TI  - Evaluation of an in vitro bloodfeeding system for testing mosquito repellents.
AB  - Median effective doses and 95% effective doses of 9 commercial mosquito
      repellents were determined for the yellow fever mosquito, Aedes aegypti, in an in
      vitro bloodfeeding test system and on the human forearm. Results obtained in the
      2 test systems did not differ significantly but, because of the inherent
      variability of repellent test data, did not always agree closely. Potential
      modifications of in vitro bloodfeeding test systems for increased accuracy,
      precision, and reliability are discussed.

PMID- 15264625
TI  - Seasonal abundance, vector behavior, and malaria parasite transmission in
      Eritrea.
AB  - Entomological studies were conducted over a 24-month period in 8 villages to
      establish the behavior patterns, seasonal densities, and variation in
      entomological inoculation rates (EIRs) of Anopheles arabiensis, the main vector
      of malaria in Eritrea. A total of 5,683 anopheline mosquitoes were collected
      through indoor sampling (1,613), human-landing catches (2,711), and outdoor pit
      shelters (1,359). Overall, An. arabiensis was the predominant species at all of
      the study sites, with its population density increasing during the rainy season.
      Peak indoor-resting densities was observed during September and October. Human
      landing indices for An. arabiensis averaged 1.9 and 3.8 per person per night in
      October and September, respectively. Peak biting and landing rates occurred
      between 2000-2200 h and 0100-0300 h. Of the total number of bites, 44.7% occurred
      between 1800 and 2300 h, and at least 56.5% of the total bites occurred outdoors,
      indicating that the species was partially exophagic. The fed to gravid ratio for
      An. arabiensis in indoor-resting collections was 2:1, indicating some degree of
      exophily. The sporozoite rates (SRs) for An. arabiensis ranged from 0.54% in the
      Anseba zone to 1.3% in the Gash-Barka zone. One mosquito each of An. d'thali (SR
      = 0.45%) and An. cinereus (SR = 2.13%) was found to be positive. Of the total
      positive An. arabiensis (n = 64), 18.2% came from human-landing collections
      outdoors. Blood-meal analysis by enzyme-linked immunosorbent assay for An.
      arabiensis indicated that this species was partially zoophilic with a human to
      bovine ratio of 2:1 being recorded. The EIR profiles indicated that malaria
      transmission is highly seasonal, increasing during the wet season and declining
      drastically during the dry season. On average, the greatest risk of infection
      occurs in Hiletsidi, in the Gash-Barka zone (6.5 infective bites per month). The
      exophilic behavior and early evening biting of An. arabiensis present obstacles
      for control with treated bed-nets and indoor residual spraying within the context
      of integrated malaria control, and call for greater focus on strategies such as
      larval control.

PMID- 15264626
TI  - Influence of temperature and concentration of VectoBac on control of the salt
      marsh mosquito, Ochlerotatus squamiger, in Monterey County, California.
AB  - Laboratory susceptibility bioassays were conducted to determine the efficacy of
      VectoBac TP (Bacillus thuringiensis var. israelensis [Bti]) at different
      concentrations and temperatures against the salt-marsh mosquito Ochlerotatus
      squamiger. Bioassays on late 3rd- and early 4th-stage larvae, read at 72 h and 14
      degrees C produced an LD90 of 0.223 mg/liter, whereas more than double this dose
      was required to produce similar mortality at 6 degrees C. A field trial in the
      winter of 2001-02 of an aerially applied VectoBac TP formulation in Salinas, CA,
      corroborated laboratory bioassay observations by producing 97-100% control of Oc.
      squamiger at 72 h postapplication. Inconsistencies in mortality with field
      applications of VectoBac TP previously observed by North Salinas Valley Mosquito
      Abatement personnel were most likely caused by uneven application rates and
      varying temperatures and water volumes.

PMID- 15264627
TI  - Effects of algae on the efficacy of Bacillus thuringiensis var. israelensis
      against larval black flies.
AB  - Personnel from several black fly control programs have reported that the efficacy
      of Bacillus thuringiensis var. israelesis (Bti) is reduced during periods when
      algal concentrations are high in the waterways. Although the reduction in Bti
      induced mortality in black fly larvae is presumed to be related to the presence
      of algae, no scientific data support this theory. In this study, 4 genera of
      algae (Microcytis, Scenedesmus, Dictrosphaerium, and Chlorella) commonly detected
      in Pennsylvania rivers where Bti-induced mortality in black fly larvae has been
      reduced were assessed to determine their respective effects on Bti-induced
      mortality by using an orbital shaker bioassay with laboratory-reared black fly
      larvae (Simulium vittatum cytospecies IS-7). A significant reduction in Bti
      induced mortality was observed when Scenedesmus was present in the flasks at
      concentrations > or = 16,000 cells/ml. The Bti-induced mortality of larvae was
      not significantly reduced when Chlorella, Dictyosphaerium, or Microcytis was
      present in the flasks, even at concentrations > or = 250,000 cells/ml. These
      results indicate that the presence of certain types of algae can reduce the
      mortality of black flies exposed to Bti. Although not clearly defined, the
      mechanisms involved may be related to algal morphology due to overall size and
      structures associated with certain types of algae, and possible interference with
      feeding.

PMID- 15264628
TI  - Efficacy and longevity of a new formulation of temephos larvicide tested in
      village-scale trials against larval Aedes aegypti in water-storage containers.
AB  - Field trials on the initial and long-term efficacy of a new formulation of
      temephos granules (1% on zeolite) applied at 1 ppm active ingredient (AI) were
      conducted in water-storage containers against Aedes aegypti in 3 villages in the
      Kanchanaburi Province in Thailand. A total of 316 water-storage containers of
      various types and sizes were included in the study. In the initial survey, we
      found that some containers were positive for larval Ae. aegypti, whereas others
      were devoid of larvae before the initiation of treatments. The containers all
      were numbered with paint and divided into 4 groups: with larvae and treated,
      without larvae and treated, with larvae untreated, and without larvae and
      untreated. Assessment of larval abundance was made 48 h after treatment and
      monthly thereafter for 5 months. Containers with larvae and that were treated
      exhibited almost complete absence of larval Ae. aegypti for 2 months, but a small
      proportion became positive after 3 months. Most of these positive containers were
      devoid of zeolite granules, which are visible in the containers. The number of
      positive containers increased in months 4 and 5, despite the fact that residues
      of temephos granules were present in some of the larvae-positive containers. The
      containers initially without larvae and treated with temephos essentially were
      devoid of larvae for 2 months. After 3, 4, and 5 months, about 6-23% of the
      containers became positive despite the fact that some had visible amounts of
      temephos granules. In the 2 control groups initially with and without larvae,
      sustained and consistent production of larvae occurred. Even in the group
      initially without a larval population, the containers became positive for larvae
      1 month after the start of the experiment and the positivity rate increased as
      the trial progressed. From these studies, the conclusion can be made that a
      single application of temephos zeolite granules at 1 ppm AI can provide highly
      satisfactory control of larval Ae. aegypti in water-storage containers for at
      least 3 months in the field under normal water-use practices.

PMID- 15264629
TI  - Diagnostic dose of synergized d-phenothrin for insecticide susceptibility testing
      by bottle bioassay.
AB  - The diagnostic dose of d-phenothrin synergized 1:1 with piperonyl butoxide for
      testing insecticide susceptibility of mosquitoes by bottle bioassay is reported
      for 2 mosquito species, Culex quinquefasciatus and Ochlerotatus taeniorhynchus.
      The diagnostic dose was defined as 2 times the 95% lethal concentration (LC95).
      LC50, LC90, and LC95 were estimated by probit analysis of dose response data.
      Procedures for diluting the commercial-grade off-the-shelf pesticide in acetone,
      treating the bottles, and calculating baseline data for insecticide-susceptible
      mosquito populations are described. The advantages and disadvantages of testing
      off-the-shelf commercial-grade pesticides that are maintained on premises by
      mosquito control programs, in contrast to using reagent-grade chemicals purchased
      from a chemical supply house, are also discussed. Data obtained by this method
      can be invaluable in making timely management decisions about the choice of
      pesticides in a control program.

PMID- 15264631
TI  - Conservation of the names Aedes albothorax, Ae. circumluteolus, and Ae.
      mcintoshi.
AB  - As a result of action by the International Commission on Zoological Nomenclature,
      the specific names Aedes albothorax (Theobald, 1907), Ae. circumluteolus
      (Theobald, 1908), and Ae. mcintoshi Huang, 1985, are conserved for common African
      mosquitoes; a neotype for albothorax is designated; and the specific name
      Banksinella pallid Theobald, 1907, is suppressed.

PMID- 15264630
TI  - First report of a kdr mutation in Anopheles arabiensis from Burkina Faso, West
      Africa.
AB  - The leu-phe kdr mutation was detected in a specimen of Anopheles arabiensis
      during an extensive survey of pyrethroid resistance in An. gambiae s.l. in
      Burkina Faso. The detection of this mutation in An. arabiensis, which had so far
      been observed only in An. gambiae s.s., is important at both epidemiologic and
      fundamental levels. It can be useful to understand the history of this gene
      throughout the range of An. gambiae complex.

PMID- 15264632
TI  - Toxorhynchites rutilus septentrionalis: new occurrences in upstate New York.
AB  - Records of Toxorhynchites rutilus septentrionalis findings in New York State are
      few, and collections north of New York City are rare. This is the 1st official
      documentation of Tx. rutilus found in upstate New York in the past 46 years and
      the farthest northern record. In 2002, immatures of Tx. rutilus were found in
      artificial containers in 2 locations in the Hudson Valley region, at Quarryville
      (Ulster County) and Blauvelt (Rockland County), NY. A study conducted at
      Quarryville in 2002 and 2003 found that breeding occurred continuously through
      the season, and that overwintering possibly could be occurring at that site.

PMID- 15264633
TI  - First record of Aedes (Stegomyia) albopictus in Belgium.
AB  - The 1st record of Aedes albopictus in Belgium was made in a village in Oost
      Vlaanderen Province. Two preimaginal stages were collected on October 31, 2000,
      in the used tire stock of a recycling company that imports tires from the USA and
      Japan. The species has reproduced on site, and local environmental conditions
      make its establishment possible. Anopheles plumbeus was a common companion
      species found in tires in high densities.

PMID- 15264634
TI  - New record, habitats, and updated checklist of the mosquitoes of Hong Kong.
AB  - Mosquito collections were carried out during April 2002 in Hong Kong. Twenty-six
      species of mosquitoes in 9 genera were collected, including 1 new record, Culex
      (Culiciomyia) nigropunctatus. Characteristics of larval habitats of these species
      are described and an updated checklist is included.

PMID- 15264635
TI  - The genus and subgenus categories within Culicidae and placement of Ochlerotatus
      as a subgenus of Aedes.
AB  - Many species of Culicidae are of major medical, veterinary, and economic
      importance. To facilitate discussion among taxonomists, medical entomologists,
      ecologists, and vector control specialists, it is essential that culicidologists
      be able to readily recognize individual genera. Adult female mosquitoes, the
      stage most often encountered in surveys, should be identifiable to genus without
      dissection with the aid of a good-quality dissecting microscope. Female adult
      specimens of Ochlerotatus and Aedes as defined by Reinert cannot be identified
      morphologically without dissection, and no distinct differences in biology,
      behavior, and ecology distinguish these 2 taxa as currently defined. Use of these
      names as genera complicates mosquito identification and interferes with
      information retrieval and communication among taxonomists, medical entomologists,
      and vector control specialists. Therefore, it is our opinion that Ochlerotatus
      Lynch Arribalzaga should be placed as a subgenus of Aedes Meigen, Aedes
      (Ochlerotatus). We believe that the usage of the genus Aedes and the subgenus Ae.
      (Ochlerotatus) should be restored to the traditional usage during the interval
      1906-2000.

PMID- 15264636
TI  - Learning to use Ochlerotatus is just the beginning.

PMID- 15264637
TI  - Orthodontic care in suburban Cuyahoga County, Ohio: who provides treatment and
      whom do they treat?
AB  - It has been reported that orthodontic services are being provided to a larger
      segment of the population by an increasing number of providers. The present study
      surveyed the dental and orthodontic experiences of 10th grade students attending
      16 public and two parochial high schools in suburban Cuyahoga County, Ohio, as
      well as two schools from the city of Cleveland. Questionnaires were distributed
      in the classroom and data obtained for 2808 students. Approximately 50% of the
      sample were girls with an average age of 15.5 +/- 0.8 years. Results of the
      survey revealed that 84% (2371/2808) had seen a dentist within the past year, and
      37% (1047/2808) of the students had received orthodontic treatment from 171
      different providers. Of those treated, 87.2% (913/1047) were treated by a
      specialist in orthodontics, 10.8% (114/1047) by a general dentist, and 0.7%
      (7/1047) by a pediatric dentist, with 1.3% missing or unknown (13/1047). Patients
      who had seen a dentist within the past year were more likely to have had
      orthodontic treatment. Only 7% of the untreated students were told by a dental
      professional that they needed braces compared with 71% of the treated group.
      Therefore, we conclude that orthodontic specialists provide most of the
      orthodontic services in the suburbs of Cuyahoga County, and visiting a general
      dentist positively influences the utilization of orthodontic services.

PMID- 15264638
TI  - The accuracy and reliability of measurements made on computer-based digital
      models.
AB  - For reasons of convenience and economy, orthodontists who routinely use and
      maintain pre- and posttreatment plaster casts are beginning to use computer-based
      digital models. The purpose of this study was to determine the accuracy
      (validity), reproducibility (reliability), efficacy, and effectiveness of
      measurements made on computer-based models. A plastic model occlusion ie,
      dentoform, served as a gold standard to evaluate the systematic errors associated
      with producing either plaster or computer-based models. Accuracy,
      reproducibility, efficacy, and effectiveness were tested by comparing the
      measurements of the computer-based models with the measurements of the plaster
      models--(1) accuracy: one examiner measuring 10 models made from a dentoform,
      twice; (2) reproducibility and efficacy: two examiners measuring 50 models made
      from patients, twice; and (3) effectiveness: 10 examiners measuring 10 models
      made from patients, twice. Reproducibility (reliability) was tested by using the
      intraclass correlation coefficient. Repeated measures of analysis of variance for
      multiple repeated measurements and Student's t-test were used to test for
      validity. Only measurements of maxillary and mandibular space available made on
      computer-based models differed from the measurements made on the dentoform gold
      standard. There was significantly greater variance for measurements made from
      computer-based models. Reproducibility was high for measurements made on both
      computer-based and plaster models. In conclusion, measurements made from computer
      based models appear to be generally as accurate and reliable as measurements made
      from plaster models. Efficacy and effectiveness were similar to those of plaster
      models. Therefore, computer-based models appear to be a clinically acceptable
      alternative to conventional plaster models.

PMID- 15264639
TI  - Rapid canine distalization using distraction of the periodontal ligament: a
      preliminary clinical validation of the original technique.
AB  - The process of rapid canine distalization through the distraction of the
      periodontal ligament is similar to the process in the midpalatal suture during
      rapid palatal expansion. Rapid canine distalization can be achieved in three
      weeks with this technique. The aim of this research was to evaluate the effects
      of rapid canine distalization on dentoalveolar tissues during the rapid
      distalization of canine teeth with semirigid, individual tooth-borne distractors.
      The study was carried out on 43 canine teeth in 18 (seven male and 11 female)
      patients who required first premolar extractions. The mean age of the patients
      was 16.7 years. The second premolars and first molars were used as anchor units.
      Orthodontic models, cephalometric and panoramic radiographs, and standard
      photographs of all the patients were taken before treatment and after the
      consolidation period. Periapical radiographies of the canines and anchor units
      were obtained once a week during the distalization period. The distractors were
      activated 0.25 mm three times a day, and the canines were distalized efficiently
      an average of three weeks. The within-group differences were evaluated with the
      Wilcoxon test. The maxillary canines were distalized an average of 5.76 mm with
      11.47 degrees distal tipping. The maxillary first molars moved mesially 0.56 mm
      and extruded 0.64 mm. The maxillary incisors showed 1.44 degrees of palatal
      tipping. The mean distal movement of the mandibular canines was 3.5 mm with 7.16
      degrees distal tipping. Anchorage loss was not observed in the mandibular first
      molars.

PMID- 15264640
TI  - Nonlinear behavior of search strategies for identifying relevant orthodontic
      articles.
AB  - The communication process with electronic literature databases permitting a
      freetext search is prone in part to nonlinear, chaotic behavior. Even very minor
      changes in the initial conditions (search query) have a dramatic impact on the
      concluding event (search outcome). This statement has been verified with
      reference to alterations to the term "orthodontic" in search strategies of
      published systematic reviews. The results showed that a variation in one letter
      led to an average of 152 papers, 81% of them of orthodontic relevance, failing to
      be localized. Yet, the opposite effect, the elimination of papers (-418), was
      also observed, confirming the underlying nonlinear pattern. Search queries for
      orthodontic articles should invariably be equipped with the robust truncation
      "orthodon*." Truncation variants of key words should be used as a matter of
      principle to verify the outcome.

PMID- 15264641
TI  - Malocclusion and temporomandibular disorder: a comparison of adolescents with
      moderate to severe dysfunction with those without signs and symptoms of
      temporomandibular disorder and their further development to 30 years of age.
AB  - A total of 1018 subjects were examined at the age of 11 years, 791 were
      reexamined at 15 years, 456 at 19 years, and 337 at 30 years. Anamnestic and
      clinical recordings of temporomandibular disorder (TMD) were made. Morphology,
      including calculation of peer assessment rating (PAR) scores, was recorded.
      Previous history of orthodontic treatment was assessed. Muscular endurance was
      recorded. The subjects completed four psychological measures. The malocclusion
      prevalence, occlusal contacts, psychological factors, and muscular endurance in
      subjects with no recorded signs and symptoms of TMD were compared with those with
      the most severe dysfunction at 19 years of age. The further development of TMD to
      30 years of age was followed. PAR scores were significantly higher in the
      subjects with the most severe dysfunction. Apart from crowding of teeth, no other
      significant differences were found between the groups with regard to separate
      malocclusions, tooth contact pattern, orthodontic treatment, or extractions. A
      greater proportion of subjects with low endurance were found in those with TMD.
      Significant associations between TMD and general health and psychological well
      being as well as the personality dimension of neuroticism and self-esteem were
      found. During the period from 19 to 30 years, the prevalence of muscular signs
      and symptoms showed considerable reduction, whereas clicking showed a slight
      increase. Locking of the joint showed a decrease from 19 to 30 years. One-quarter
      of the TMD subjects showed complete recovery. Thus, orthodontic treatment seems
      to be neither a major preventive nor a significant cause of TMD.

PMID- 15264642
TI  - The G-Axis: a growth vector for the mandible.
AB  - On the basis of the G-point, defined as the center of the largest circle that is
      tangent to the internal inferior, anterior, and lingual surfaces of the
      mandibular symphysis in the sagittal view, a growth axis and its direction are
      described for each gender from age six to 19.25 years. Incremental growth along
      the G-Axis, defined by Sella-G-point, is described by regression formulas with
      correlation coefficients of 0.673 for female subjects and 0.749 for male
      subjects. The vector (direction) of the growth axis, defined by the angle alpha
      ((G-Axis)-(S-N)) does not materially alter in the age range studied. At age six
      in female subjects the angle alpha is 67.16 degrees +/- 3.03 degrees and at age
      19.25 it is 66.87 degrees +/- 3.03 degrees, whereas in male subjects it is 66.12
      degrees +/- 4.00 degrees and 67.93 degrees +/- 4.00 degrees, respectively. These
      changes and gender differences are not clinically significant. The data is based
      on 444 serial lateral cephalograms of 24 female subjects and 24 male subjects.
      The G-Axis incremental growth change and its vector offer an improved means of
      quantifying complex mandibular growth in the sagittal plane by using
      cephalometric measurements relative to and correlated with other craniofacial
      structures.

PMID- 15264643
TI  - Angular changes and their rates in concurrence to developmental stages of the
      mandibular second premolar.
AB  - In the early developmental stage of the mandibular second premolar (MnP2), it is
      not unusual to find the tooth extremely angulated to the lower border of the
      mandible, as seen in the panoramic roentgenogram. On eruption, the tooth, in most
      cases, is close to being upright. However, impaction or other types of
      malocclusions due to its ectopic eruption are not rare. This study follows the
      angular changes of the MnP2 during development. Two hundred two panoramic
      roentgenograms of 101 patients were retrospectively analyzed. All patients had
      two sequential films with a minimal time interval of nine months. Each MnP2 was
      traced, and its developmental stage as well as its angulation to the lower border
      of the mandible was registered. We found that normally more MnP2 are distally
      (56.5%) than mesially (25%) inclined. There is a statistically significant
      difference in the inclination of the teeth during their development from stage D
      to stage F (D = 75.17 degrees +/- 15.25 degrees, E = 79.35 degrees +/- 12.18
      degrees, F = 83.38 degrees +/- 10.79 degrees). The average amount of total
      angular change rate of the MnP2s from stage D to stage G is 0.09 +/- 0.25
      degrees/mo, and the absolute angular change rate is 0.19 +/- 0.25 degrees/mo.

PMID- 15264644
TI  - Agenesis of third molar germs depends on sagittal maxillary jaw dimensions in
      orthodontic patients in Japan.
AB  - The aim of this study was to determine the correlation between congenitally
      missing third molar tooth germs and sagittal maxillomandibular jaw dimensions in
      orthodontic patients in Japan. The subjects were 391 patients from the
      orthodontic clinic of the Hokkaido University Dental Hospital who were less than
      15 years of age. Assessments were made from panoramic radiographs and lateral
      cephalograms. The subjects were divided into a maxillary/mandibular third molar
      absent and an existent group. The ANB angle and the sagittal dimensions of the
      nasal floor (ANS-PNS), maxillary basal bone (Mx), mandibular corpus (Go-Pog), and
      mandibular basal bone (Mn) were measured. Logistic regression analysis was used
      to estimate associations between third molar agenesis and these measures. The
      following results were obtained: (1) The frequency of the maxillary third molar
      agenesis significantly increased with decreasing Mx (odds ratio = 0.559, 95%
      confidence interval = 0.377 - 0.829). The frequency of the mandibular third molar
      agenesis also increased with decreasing Mx (odds ratio = 0.532, 95% confidence
      interval = 0.330 - 0.856). (2) There were no significant correlations between Mn
      and mandibular third molar agenesis. These results suggest that agenesis of third
      molar germs does not depend on anteroposterior dimensions of the mandible but
      depends on anteroposterior dimensions of the maxilla in Japanese orthodontic
      patients.

PMID- 15264645
TI  - Heterogeneity in vertical positioning of the hyoid bone in relation to
      genioglossal activity in men.
AB  - The aim of this study was to investigate whether there is any relationship among
      genioglossus (GG) baseline electromyographic (EMG) activity, upper airway
      resistance, and sex. We hypothesized that GG baseline EMG activity and its
      response to pharyngeal partial occlusion may be heterogeneous in men but
      homogeneous in women. Lateral head roentgenograms were obtained in the upright
      standing position with the head at natural posture from age-matched, healthy, 16
      men and 15 women. A miniature balloon was placed in the retroglossal pharynx, and
      a record of GG EMG response was measured. The database was divided by sex and
      further categorized based on the increment of GG EMG response to inflation of the
      balloon. Both sexes included responsive subjects showing a greater GG EMG
      activity increase than the mean values and a counterpart, ie, a nonresponsive
      group. When the two subgroups were compared, the hyoid bone of the responsive
      subjects positioned more inferiorly than that of nonresponsive subjects in men (P
      < .05). When men and women were compared, most cephalometric measurements were
      significantly larger in the male responders, but no difference was shown in the
      nonresponders. We concluded that men with a lower hyoid bone show greater GG
      reflexive response to the partial oropharyngeal obstruction.

PMID- 15264646
TI  - Investigation of the changes in the positions of upper and lower incisors,
      overjet, overbite, and irregularity index in subjects with different depths of
      curve of Spee.
AB  - The aim of this study was to investigate the relationship between the depth of
      the curve of Spee and positions of upper and lower incisors, overjet, overbite,
      and anterior lower crowding. The material consisted of lateral head films and
      dental casts of 137 untreated adolescent subjects, 76 girls and 61 boys, aged 13
      to 16 years. The subjects were divided into three groups with normal Spee, flat
      Spee, and deep Spee and were compared with one another. Differences between the
      Spee groups and between sexes were assessed by means of analysis of variance and
      a post hoc multiple comparison test. In addition, correlation coefficients
      between the depth of curve of Spee and other variables were calculated. Finally,
      cephalometric measurements for all subjects were subjected to a multiple
      regression analysis, with the depth of curve of Spee as the dependent variable.
      The results showed that there were no statistically significant differences in
      the positions of upper and lower incisors and anterior lower crowding among the
      Spee groups. However, overjet and overbite demonstrated significant differences
      among the groups. Statistically significant correlations were found between the
      depth of curve of Spee and overjet and overbite. Multiple linear regression
      analysis revealed that chronological age and all other variables used in the
      study could account for only 28.7% of the total variance of the curve of Spee.
      The overbite alone explained 17.3% of the total variance of the curvature.

PMID- 15264647
TI  - Comparison of dental arch and alveolar widths of patients with Class II, division
      1 malocclusion and subjects with Class I ideal occlusion.
AB  - This study evaluates dental arch and alveolar widths of patients with Class II,
      division 1 malocclusion. Thirty female patients with Class II, division 1
      malocclusion were compared with 30 female subjects with Class I ideal occlusion.
      Patients with posterior crossbites even in a single tooth were excluded from the
      study. According to our results, arch widths measured between maxillary second
      premolars and maxillary first molars were found narrower in the Class II,
      division 1 group, and mandibular intercanine widths were narrower in the Class I
      group. Interalveolar widths showed no difference between the groups. These
      results suggested that transverse discrepancy in Class II, division 1 patients
      originated from upper posterior teeth and not from the maxillary alveolar base.
      Therefore, slow maxillary expansion rather than rapid maxillary expansion may be
      considered before or during the treatment of Class II, division 1 patients.

PMID- 15264648
TI  - Correlation of the cranial base angle and its components with other
      dental/skeletal variables and treatment time.
AB  - Many authors have studied the correlation of cranial base flexure and the degree
      of mandibular prognathism and classification of malocclusion. This indicates that
      the cranial base flexure may or may not have an effect on the degree of
      mandibular prognathism and classification of malocclusion. This study evaluates
      the correlation of the pretreatment cranial base angle and its component parts to
      other dental and skeletal cephalometric variables as well as treatment time. The
      sample consisted of 99 Angle Class II and Class I malocclusions treated in the
      mixed dentition with cervical headgear and incisor bite plane. Thirty of the
      patients required full appliance treatment. Treatment duration averaged 4.3 years
      (SD, 1.5 years). Only the starting cephalograms were used to acquire linear,
      proportional, and angular cranial base dimensions using Ba-S-N (total cranial
      base), Ba-S/FH (posterior cranial base), and SN/FH (anterior cranial base).
      Pearson product moment correlation coefficients were computed and used to assess
      the association of the following skeletal and dental variables: N-Pg/FH, MP/FH, Y
      axis/FH, U1/L1, L1/MP, A-NPg mm, A-Perp, B-Perp, and treatment time with the
      cranial base measurements. Significance was determined only when the confidence
      level was P < .05. Although there was no significant correlation of BaSN or SN/FH
      with NPg, the angular BaS/FH, linear BaS mm, and proportional length of BaS %BaN
      were all statistically negatively correlated to the facial angle. This indicates
      that the posterior cranial base leg is the controlling factor in relating the
      cranial base to mandibular prognathism.

PMID- 15264649
TI  - Growth and treatment changes distal to the mandibular first molar: a lateral
      cephalometric study.
AB  - This study examined space changes occurring distal to the mandibular first molar
      in growing patients treated using two different approaches. Two groups of 50
      patients were selected for the study. The patients in group I were treated with
      the extraction of mandibular second premolars, whereas those in group II were
      treated without mandibular premolar extractions, by holding E-spaces with utility
      arches. Lateral cephalograms taken before and after treatment were used to
      measure space changes within the mandible. Follow-up written treatment records
      and radiographs were also examined to ascertain whether the mandibular third
      molars were ultimately extracted or retained. A greater mean space increase
      between Xi point and the mandibular first molar was found in boys and girls
      treated with second premolar extractions. The mean space increase between Xi
      point and the mandibular first molar, as well as the average increase in total
      mandibular length, was greater in boys than in girls for both treatment
      modalities. This reflects a greater amount of growth in boys during the treatment
      period. The greater mean space increase in the groups treated with second
      premolar extractions could be attributed to the fact that the first molar
      generally moved further mesially during treatment in the extraction subjects,
      whereas in the E-space subjects, the first molars were perhaps held back. It was
      noted that the mandibular third molars were ultimately more likely to have been
      extracted in the E-space groups than in the second premolar extraction groups
      within this sample.

PMID- 15264650
TI  - Comparison of two different gingivectomy techniques for gingival cleft treatment.
AB  - Interdental clefts or invaginations contribute to orthodontic relapse and poor
      periodontal health in extraction cases. These clefts or invaginations can be
      removed both by electrosurgical or conventional surgical gingivectomy techniques.
      This study investigates and compares the efficacy of two different techniques to
      remove gingival clefts with respect to periodontal health and patient tolerance.
      Twenty-two patients (mean age, 15.7 years) with bilateral gingival clefts
      participated in this study. In each patient, the gingival invaginations were
      removed by gingivectomy using electrosurgery on one side and conventional surgery
      on the contralateral side. The length and depth of the invaginations, the
      gingival index of the adjacent teeth, and the changes in visual analogue scale
      scores were recorded before and after the operation for both groups. Mann-Whitney
      U-test and Wilcoxon tests were used to analyze the data statistically. The
      results showed significant improvement in invagination depth and length and
      gingival index scores for both techniques. There were no statistical differences
      between the two gingivectomy techniques with respect to gingival health and
      patient tolerance. Both techniques can be used to remove the gingival
      invaginations efficiently.

PMID- 15264651
TI  - The use of skeletal anchorage in open bite treatment: a cephalometric evaluation.
AB  - The aims of the present study were to assess the effectiveness of skeletal
      anchorage for intrusion of maxillary posterior teeth, to correct open bite
      malocclusion, and to evaluate the usage of titanium miniplates for orthodontic
      anchorage. Anterior open bite is one of the most difficult malocclusions to treat
      orthodontically. Currently, surgical impaction of the maxillary posterior segment
      is considered to be the most effective treatment option in adult patients.
      Various studies have reported the use of implants as anchorage units at different
      sites of midfacial bones for orthodontic tooth movement. The zygomatic buttress
      area could be a valuable anchorage site to achieve intrusion of maxillary
      posterior teeth. Ten patients, 17 to 23 years old and characterized with an
      anterior open bite and excessive maxillary posterior growth, were included in
      this preliminary study. Titanium miniplates were fixed bilaterally to the
      zygomatic buttress area, and a force was applied bilaterally with nine mm Ni-Ti
      coil springs between the vertical extension of the miniplate and the first molar
      buccal tube. The results showed that, with the help of skeletal anchorage,
      maxillary posterior teeth were intruded effectively. As compared with an
      osteotomy, this minimally invasive surgical procedure eased treatment and reduced
      treatment time and did not require headgear wear or anterior box elastics for
      anterior open bite correction. In conclusion, the zygomatic area was found to be
      a useful anchorage site for intrusion of the molars in a short period of time.

PMID- 15264652
TI  - Color stability of orthodontic adhesive resins.
AB  - Color alteration of adhesive during treatment and after debonding may be
      implicated in long-term enamel discoloration. The aim of this study was to assess
      the color stability of light-cured and chemically cured adhesives subjected to
      artificial photoaging. Disk-shaped specimens of adhesives were colorimetrically
      evaluated before and after artificial photoaging using an ISO-recommended
      protocol. The measurement variable was the color change (deltaE) of adhesives
      induced by artificial, accelerated photoaging. The deltaE values derived from the
      two color recordings for the materials at pre- and postaging intervals were
      statistically analyzed with a one-way analysis of variance (ANOVA), with the
      adhesive brand serving as a discriminating variable. Differences among groups
      were further investigated using the Tukey multiple comparisons test (alpha =
      .05). To establish the statistical significance of the difference of the deltaE
      values of each adhesive and the deltaE threshold for clinical detection, a paired
      t-test was used (P = .05). All adhesives exhibited color change, which in some
      cases exceeded the clinically detectable color change limit. The extent of the
      color alterations of aged bonding systems may contribute to enamel discoloration
      after treatment.

PMID- 15264653
TI  - Elemental composition of brazing alloys in metallic orthodontic brackets.
AB  - The aim of this study was to assess the elemental composition of the brazing
      alloy of representative orthodontic brackets. The brackets examined were Gemini
      (3M, Unitec, Monrovia, Calif), MicroLoc (GAC, Bohemia, NY), OptiMESHxrt (Ormco,
      Glendora, Calif), and Ultratrim (Dentarum, Ispringen, Germany). Four metallic
      brackets for each brand were embedded in epoxy resin and after metallographic
      grinding and polishing were cleaned in a water ultrasonic bath. Scanning electron
      microscopy and energy-dispersive x-ray microanalysis (EDS) were used to assess
      the quantitative composition of the brazing alloy. Four EDS spectra were
      collected for each brazing alloy, and the mean value and standard deviation for
      the concentration of each element were calculated. The elemental composition of
      the brazing alloys was determined as follows (percent weight): Gemini: Ni = 83.98
      +/- 1.02, Si = 6.46 +/- 0.37, Fe = 5.90 +/- 0.93, Cr = 3.52 +/- 0.34; MicroLoc:
      Ag = 42.82 +/- 0.18, Au = 32.14 +/- 0.65, Cu = 24.53 +/- 0.26, Mg = 1.12 +/-
      0.33; OptiMESHxrt: Au = 67.79 +/- 0.97, Fe = 15.69 +/- 0.29, Ni = 13.01 +/- 0.93,
      Cr = 4.01 +/- 0.35; Ultratrim: Ag = 87.97 +/- 0.33, Cu = 10.51 +/- 0.45, Mg =
      1.29 +/- 0.63, Zn = 1.13 +/- 0.24. The findings of this study showed that
      different brazing materials were used for the different brands, and thus
      different performances are expected during intraoral exposure; potential effects
      on the biological properties also are discussed.

PMID- 15264654
TI  - The effect of variation in mesh-base design on the shear bond strength of
      orthodontic brackets.
AB  - This study compared the shear bond strengths of two metallic orthodontic
      brackets, one with a single-mesh bracket base and the other with a double-mesh
      bracket base. The Transbond XT adhesive system was used to bond all brackets to
      the teeth. Two types of brackets were compared, ie, 20 Ovation metal bracket
      series, with a double-mesh base (Super-mesh) and an 81.50 gauge (0.126 inch), and
      20 Victory series metal brackets that have a miniature single-mesh base. The
      teeth were bonded and debonded within half an hour from the initial bonding. The
      enamel surface was examined under 10x magnification to determine how much
      residual adhesive remained on the tooth. Student's t-test was used to compare the
      shear bond strength of the two groups. Chi-square test was used to compare the
      adhesive remnant index (ARI) scores for the two bracket types. The mean shear
      bond strength for the double-mesh brackets was 5.2 +/- 3.9 MPa and for the single
      mesh brackets was 5.8 +/- 2.8 MPa. The t-test comparisons indicated that they
      were not significantly different from each other (P = .157). The ARI comparisons
      indicated that both bracket types had similar bracket failure modes and were not
      significantly different from each other (chi2 = 2.0, P = .5). These results
      indicated that single- and double-mesh bracket bases have comparable shear bond
      strength and bracket failure modes.

PMID- 15264655
TI  - In vitro evaluation of shear bond strengths and in vivo analysis of bond survival
      of indirect-bonding resins.
AB  - In this study we evaluate the shear bond strengths (SBS) of indirect-bonding
      systems available on the market. For the in vitro study, 60 extracted premolars
      were divided into three groups. In indirect group I, the brackets were bonded to
      models using Therma Cure laboratory resin and transferred to the teeth using
      Custom IQ resin for indirect bonding. For indirect group II, the teeth were
      attached to models using Transbond XT and transferred using Sondhi Rapid Set. In
      the direct-bonding group, the brackets were bonded to teeth directly using
      Transbond XT The SBS were evaluated, and the comparisons were made. In the in
      vivo study, left half of the upper arch and right half of the lower arch were
      bonded using Sondhi's indirect-bonding resin and right half of the upper arch and
      left half of the lower arch were bonded using Therma Cure as a laboratory resin
      and Custom IQ as a clinical bonding resin. The failure rates of the brackets were
      followed for nine months. Analysis of variance and Tukey tests were performed.
      Mean SBS values (MPa) were 10.3 +/- 4.2, 6.1 +/- 1.6, and 12.8 +/- 5.4 for the
      indirect groups I and II and for the direct-bonding group, respectively. There
      were no significant differences between indirect group I and direct group (P >
      .05), whereas both yielded significantly higher SBS values compared with indirect
      group II. In vivo bond survival evaluation showed no differences between the two
      indirect-bonding systems available.

PMID- 15264656
TI  - Evaluation of modifying the bonding protocol of a new acid-etch primer on the
      shear bond strength of orthodontic brackets.
AB  - The purpose of the study was to evaluate the shear bond strength of orthodontic
      brackets when light curing both the self-etch primer and the adhesive in one
      step. Fourty eight teeth were bonded with self-etch primer Angel I (3M/ESPE, St
      Paul, Minn) and divided into three groups. In group I (control), 16 teeth were
      stored in deionized water for 24 hours before debonding. In group II, 16 teeth
      were debonded within half-an-hour to simulate when the initial archwires were
      ligated. In group III, 16 additional teeth were bonded using exactly the same
      procedure as in groups I and II, but the light cure used for 10 seconds after
      applying the acid-etch primer was eliminated, and the light cure used for 20
      seconds after the precoated bracket was placed over the tooth. This saved at
      least two minutes of the total time of the bonding procedure. The teeth in this
      group were also debonded within half-an-hour from the time of initial bonding.
      The teeth debonded after 24 hours of water storage at 37 degrees C had a mean
      shear bond strength of 6.0 +/- 3.5 MPa, the group that was debonded within half
      an-hour of two light exposures had a mean shear bond strength of 5.9 +/- 2.7 MPa,
      and the mean for the group with only one light cure exposure was 4.3 +/- 2.6 MPa.
      Light curing the acid-etch primer together with the adhesive after placing the
      orthodontic bracket did not significantly diminish the shear bond strength as
      compared with light curing the acid-etch primer and the adhesive separately.

PMID- 15264657
TI  - Effectiveness of a hydrophilic primer when different antimicrobial agents are
      mixed.
AB  - The purpose of this study was to determine whether different types of
      antimicrobial agents with hydrophilic primer applied to etched enamel surfaces
      will affect the shear bond strength (SBS) and the bracket/adhesive failure modes
      of metallic orthodontic brackets. Eighty noncarious human premolars were divided
      into four groups of 20 each. A composite resin (Transbond XT) was used to bond
      stainless steel brackets. Teeth in the first group were used as a control and
      bonded with standard procedures. For the other three groups, mixtures containing
      a hydrophilic primer (Transbond MIP) and one of three anti-microbial agents were
      prepared (Cervitec: in 1:2 ratio; chlorhexidine mouthwash and EC40 varnish in 1:1
      ratio). These mixtures were applied to the etched enamel surfaces and thoroughly
      light cured for 20 seconds, and the brackets were bonded and light cured for 40
      seconds. The SBS values of these brackets (Mpa) were recorded using a universal
      testing machine. Adhesive Remnant Index scores were determined after failure of
      the brackets. Data were analyzed using analysis of variance (ANOVA), Tukey
      honestly significant difference, and chi-square tests. Results of ANOVA revealed
      statistically significant differences in bond strengths among the various groups
      tested (P < .05). The bond strength values in these four groups compared
      favorably with those from other studies and the minimal bond strength values that
      are clinically acceptable. However, results of this study demonstrated that
      groups 1 (control) and 2 (Cervitec varnish) had higher SBS values than the other
      applications. Application of different antimicrobial agents may result in
      differences in the site of failure.

PMID- 15264658
TI  - Premaxillary distraction osteogenesis with an individual tooth-borne appliance.
AB  - Distraction osteogenesis defines a technique of bone generation and
      osteosynthesis by the distraction of native preexisting bone. The technique
      offers a promising treatment alternative for patients with maxillary hypoplasia
      and a retrognathic mandible. In this case report, the steps in the treatment of
      an 18.2-year-old girl with premaxillary hypoplasia and anterior crossbite are
      described. The patient was treated with a distraction osteogenesis technique, and
      premaxillary advancement was performed using an individual tooth-borne
      distraction device. The surgical operation consisted of a classical segmental
      maxillary osteotomy carefully respecting the palatal periosteum. The distractor
      was cemented in the mouth after the surgical procedures. The patient was observed
      during a seven-day latency period, after which the device was activated 0.5 mm
      every 12 hours. The anterior crossbite was eliminated in one week, and the
      treatment was finished with fixed orthodontic appliances.

PMID- 15264659
TI  - Macrophage behavior on surface-modified polyurethanes.
AB  - Adherent macrophages and foreign body giant cells (FBGCs) are known to release
      degradative molecules that can be detrimental to the long-term biostability of
      polyurethanes. The modification of polyurethanes using surface modifying
      endgroups (SMEs) and/or the incorporation of silicone into the polyurethane soft
      segments may alter macrophage adhesion, fusion and apoptosis resulting in
      improved long-term biostability. An in vitro study of macrophage adhesion, fusion
      and apoptosis was performed on polyurethanes modified with fluorocarbon SMEs,
      polyethylene oxide (PEO) SMEs, or poly(dimethylsiloxane) (PDMS) co-soft segment
      and SMEs. The fluorocarbon SME and PEO SME modifications were shown to have no
      effect on macrophage adhesion and activity, while silicone modification had
      varied effects. Macrophages were capable of adapting to the surface and adhering
      in a similar manner to the silicone-modified and unmodified polyurethanes. In the
      absence of IL-4, macrophage fusion was comparable on the modified and unmodified
      polyurethanes, while macrophage apoptosis was promoted on the silicone modified
      surfaces. In contrast, when exposed to IL-4, a cytokine known to induce FBGC
      formation, silicone modification resulted in more macrophage fusion to form
      foreign body giant cells. In conclusion, fluorocarbon SME and PEO SME
      modification does not affect macrophage adhesion, fusion and apoptosis, while
      silicone modification is capable of mediating macrophage fusion and apoptosis.
      Silicone modification may be utilized to direct the fate of adherent macrophages
      towards FBGC formation or cell death through apoptosis.

PMID- 15264660
TI  - The effect of pH on the LCST of poly(N-isopropylacrylamide) and poly(N
      isopropylacrylamide-co-acrylic acid).
AB  - Poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide-co-acrylic
      acid) (P(NIPAAm-co-AAc)) hydrogels are synthesized by irradiating the aqueous
      solutions of NIPAAm and NIPAAm/AAc with 60Co gamma-ray. The effects of pH on the
      swelling ratio and on the lower critical solution temperature (LCST) are studied
      by determining the dependence of swelling ratio on temperature in different pH
      butter solutions. Differential scanning calorimetry (DSC) is applied in
      determination of the LCST of the hydrogels. Fourier transform infrared (FT-IR)
      spectrometry is used in the comparison of hydrogels swelled in various pH
      conditions. As a result, PNIPAAm was found to be a pH-sensitive hydrogel and the
      LCST of the PNIPAAm and P(NIPAAm-co-AAc) hydrogels are influenced by pH.

PMID- 15264661
TI  - Amido-modified polylactide for potential tissue engineering applications.
AB  - Poly(ester amide) copolymers based on L-lactide (2) and a new depsipeptide (1)
      were prepared by ring opening polymerization in the presence of Sn(Oct)2 as the
      catalyst. Variable monomer feed ratios up to 2.3 mol% 1 afforded copolymers
      containing ester and amido functional groups in the backbone. Lower glass
      transition temperatures and reduced crystallization kinetics and crystallinity
      compared to homo-polylactide (PLA) was achieved with low levels of amido
      incorporation. A reactivity comparison between enchainment of 2 and 1 was
      determined using in situ infrared spectroscopy. An increase in shear viscosity
      was observed with the increase of 1 content as determined by rheology studies.
      Cellular compatibility of the co-polymers was investigated by seeding D1 mouse
      stem cells onto films and characterizing cell morphology by optical microscopy.
      Preliminary results indicate that these novel materials exhibit reduced cell
      attachment compared to PLA and, pending further exploration, may have potential
      use in biomedical applications.

PMID- 15264662
TI  - Novel carboxymethylcellulose-based microporous hydrogels suitable for drug
      delivery.
AB  - Several materials capable of acting as structures for controlled release were
      analysed for the fabrication of matrices. Among those used, hydrophilic
      polysaccharides appeared to be the most suitable materials.
      Carboxymethylcellulose (a semi-synthetic polysaccharide) was chemically cross
      linked with a 60% and 90% cross-linking degree in order to obtain hydrogels and
      utilised as matrix for the realisation of controlled drug release systems. The
      morphology of the gels was changed in order to obtain a microporous structure
      with different porosity (14, 30 and 40 microm). The obtained porous matrices were
      characterised in terms of pore density, dimension and swelling behaviour. The
      influence of both the pore dimension and technique of loading on the release
      kinetics was analysed. By increasing the pore dimension the release of ibuprofen
      lysin was slower. Inducing the microporous structure after the loading of the
      hydrogel with the drug resulted in a slower release.

PMID- 15264663
TI  - PEGylated dextran as long-circulating pharmaceutical carrier.
AB  - Dextran-polyethylene glycol (PEG) conjugates were synthesized by activating
      dextran hydroxy groups with carbonyldiimidazole, introducing amino groups by
      attaching ethylenediamine, and reacting amino groups with a succinimidyl
      activated derivative of PEG. Conjugates with an average of 12 and 21 PEG (5 kDa)
      residues per single dextran (73 kDa) molecule were prepared. These conjugates
      have circulation half-lives of 5.3 h and 7.0 h, respectively, compared to 4.0 h
      for non-PEGylated dextran. The modification of dextran with PEG inhibits the
      uptake of polymer by the major organ of the reticuloendothelial system, the
      liver. Dextran-PEG conjugates may represent a convenient platform for long
      circulating pharmaceutical preparations.

PMID- 15264664
TI  - Hydrogen-bonding-driven spontaneous gelation of water-soluble phospholipid
      polymers in aqueous medium.
AB  - It has been found that mixing of two kinds of water-soluble phospholipids
      polymers, such as poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic
      acid) (PMA) and poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl
      methacrylate) (PMB), spontaneously forms a hydrogel in aqueous medium at room
      temperature without any chemical treatment. However, the mechanism of spontaneous
      gelation has not been clarified yet. The purpose of this study is to investigate
      the gelation mechanism of the hydrogel. Moreover, effects of ions on gelation and
      dissolution behavior were observed. We investigated the mechanism of the hydrogel
      formation by spectroscopic techniques and a rheological method with attention to
      the interactions between polymer chains. Both Raman spectroscopic analysis and FT
      IR analysis revealed that carboxyl groups in methacrylic acid (MA) formed dimer
      when two polymer solutions were mixed, and the results of the rheological study
      showed dissociation of carboxyl groups caused dissolution of the hydrogel. Thus,
      the gelation occurred due to the formation of dimers by hydrogen bonding which
      acts as a physical cross-linking of polymer chains. The hydrogel dissolved in a
      large amount of aqueous medium. We also observed the addition of inorganic salts
      during the preparation of the hydrogel affected the gelation and dissolution
      behaviors by a rheological and a weight measuring method, respectively. The
      gelation period became longer in the presence of NaCl and CaCl2 compared with
      that in the absence of these salts. NaCl and CaCl2 disturbed the formation of
      hydrogen bonding between carboxyl groups by stabilization of carboxylate anion of
      the MA units. On the other hand, addition of FeCl3 made the gelation period
      shorter and stabilized the hydrogel in the aqueous medium. This is because FeCl3
      can suppress dissociation of the carboxyl groups by acidic condition of FeCl3
      aqueous solution and cross-link the carboxylate anions in the PMA effectively.

PMID- 15264665
TI  - Manufacture of elastic biodegradable PLCL scaffolds for mechano-active vascular
      tissue engineering.
AB  - A soft and very elastic poly(lactide-co-epsilon-caprolactone) (PLCL)(50:50, Mn
      185 x 10(3)) was synthesized. Tubular scaffolds were prepared by an extrusion
      particulate leaching method for mechano-active vascular tissue engineering. The
      copolymer was very flexible but completely rubber-like elastic. Even the high
      porous PLCL scaffolds (90% salt wt) exhibited 200% elongation, but recovery over
      85% in a tensile test. Moreover, the PLCL scaffolds maintained their high
      elasticity also in culture media under cyclic mechanical strain conditions. The
      highly porous scaffold (90% salt wt) withstood for an initial 1 week without any
      deformation and sustained for 2 weeks in culture media under cyclic stress of 10%
      amplitude and at 1 Hz frequency which are similar to the natural vascular
      conditions. Vascular smooth muscle cells (VSMCs) were seeded on to the PLCL
      scaffolds. The cell adhesion and proliferation on the scaffolds of various pore
      size were increased with increasing pore size. For the pore sizes of 50-100
      microm, 100-150 microm, 150-200 microm and 200-250 microm, the ratios of cell
      numbers were about 1:1.2:1.9:2.2, respectively, at both 12 h and 5 days.
      Similarly, the higher porous scaffolds exhibited more cell adhesion and
      proliferation compared to lower porous one, where the effect was more pronounced
      in the longer proliferation period. SMC-seeded scaffolds were implanted
      subcutaneously in athymic nude mice to confirm the biocompatibility. Such a high
      elastic property and proper biocompatibility to SMCs of PLCL scaffolds prepared
      in this study will be very useful to engineer SM-containing tissues such as blood
      vessels under mechanically dynamic environments (mechano-active tissue
      engineering).

PMID- 15264666
TI  - IgG responses to intranasal immunization with cholera-toxin-immobilized polymeric
      nanospheres in mice.
AB  - IgG responses to antigen-nanosphere hybrids were studied in mice. Cholera toxin
      (CT) was covalently immobilized onto the surface of polymeric nanospheres (NS)
      with a nanophase-separated structure consisting of a polystyrene core and a
      poly(methacrylic acid) graft corona. Reaction conditions favoring the dehydroxide
      condensation reaction of the amino group of the CT with the carboxyl group of NS
      effectively immobilized CT onto their surface. When CT-immobilized nanospheres
      (CT-NS) were suspended in aqueous solution and administrated to mice either
      intranasally or intramuscularly, serum IgG titers elevated with increasing time
      and reached a maximum level at 8 weeks after immunization. On the other hand,
      intranasal administration of CT alone induced an even higher serum IgG titer than
      that of CT-NS at 4 weeks. However, the titer gradually decreased thereafter.
      Thus, polymeric NS may be an effective substrate to covalently immobilize antigen
      on their surface, steadily inducing a high level of IgG production in response to
      the intranasal administration.

PMID- 15264667
TI  - Enhanced ileal absorption of a hydrophilic macromolecule, pentosan polysulfate
      sodium (PPS).
AB  - An in situ gelling, bioadhesive liquid formulation was developed to enhance the
      bioavailbility (BA) of a polysaccharide, pentosan polysulfate sodium (PPS). The
      formulation was tested to determine its bioavailability enhancement in a non
      flush/non-ligated rat ileal model. A potent synergistic effect was found with a
      gelling agent Cremophor and a permeation enhancer sodium salicylate. The absolute
      bioavailabilities were 1.9%, 4.6%, 6.3% and 46.4%, respectively, for the PPS
      solution in saline, sodium salicylate/PPS, Cremophor/PPS and Cremophor/sodium
      salicylate/PPS. Therefore, we successfully demonstrated the approach of utilizing
      an in situ gelling/bioadhesive liquid carrier to enhancing the bioavailability of
      a hydrophilic macromolecule at the distal small intestine.

PMID- 15264668
TI  - Development of perforated microthin poly(epsilon-caprolactone) films as matrices
      for membrane tissue engineering.
AB  - The design and fabrication of thin films based on bioresorbable polymers such as
      poly(epsilon-caprolactone) (PCL) has been the focus of a part of current
      biomedical research, especially as matrices for membrane tissue engineering. We
      have successfully developed perforated microthin PCL membrane for this purpose.
      Two critical issues are the control of moisture permeability and understanding
      the degradation of PCL microthin film. In order to increase the moisture
      permeability. PCL films were biaxially stretched to a thickness of 10 +/- 3
      microm and perforated with uniform array of holes (180-275 microm) using a Sony
      Robotic system. After perforation, the water vapour transmission rate was
      increased by 50% to a value of 47.6 +/- 2.7 g/h per m2. Accelerated hydrolytic
      degradations were performed in 5 M NaOH. The degraded samples were characterised
      for changes in weight, surface morphology, mechanical properties, crystallinity
      and molecular weight. Hydrolytic degradation commenced with random chain scission
      of backbone ester bonds on the film surface and followed by loss of material due
      to surface erosion. In general, the perforated films degraded faster than the
      unperforated microthin films. Scanning electron microscopic images showed that
      surface erosion led to extensive formation of micropores, microcracks and
      increased in surface roughness.

PMID- 15264669
TI  - Influence of dietary vitamin E and C supplementation on vitamin E and C content
      and thiobarbituric acid reactive substances (TBARS) in different tissues of
      growing pigs.
AB  - To investigate the influence and possible interactions of dietary vitamin E and C
      supplementation on vitamin content of both vitamins and oxidative stability of
      different pork tissues 40 Large White barrows from 25 kg to 106 kg were allocated
      to four different cereal based diets: Basal diet (B), dl-alpha-tocopherylacetate
      + 200 mg/kg (E), crystalline ascorbic acid + 300 mg/kg (C) or both vitamins (EC).
      At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham
      and M. tongissimus dorsi were obtained. Growth performance of the pigs and
      carcass characteristics were not influenced by feeding treatments. Dietary
      vitamin E supplementation had a significant effect on the vitamin E and alpha
      tocopherol concentration in all investigated tissues. Backfat outer layer, liver,
      spleen, kidney and heart had higher vitamin E concentrations than ham and M.
      longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced
      vitamin E levels except for ham samples. Therefore, some synergistic actions
      without dietary vitamin E supplementation between the two vitamins could be
      shown. The vitamin C concentration and TBARS were increased or at least equal in
      all tissues due to vitamin C supplementation. Dietary alpha-tocopherol
      supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde
      0.35 mg/kg in B vs. 0.28 mg/kg in E), but increased in heart and ham. When both
      vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and
      backfat outer layer, equal in heart and higher in liver and ham compared to a
      single vitamin C supplementation. Rancimat induction time of backfat outer layer
      was 0.3 h higher in C compared to B and 0.17 h higher in EC than in E.
      Correlations between levels of both vitamins were positive for kidney (r =
      0.169), M. longissimus dorsi (r = 0.499) and ham (r = 0.361) and negative for
      heart (r = -0.350). In liver and spleen no interaction could be found. In backfat
      outer layer vitamin E was positively correlated with rancimat induction time (r =
      0.550) and negatively with TBARS (r = -0.202), but provided no evidence that
      dietary vitamin E supply led to better oxidative stability.

PMID- 15264670
TI  - Performance of rabbits and oxidative stability of muscle tissues as affected by
      dietary supplementation with oregano essential oil.
AB  - The effect of dietary supplementation with oregano essential oil on the
      performance of rabbits, and the susceptibility of the produced raw and thermally
      treated muscle tissue to lipid oxidation during refrigerated storage, were
      investigated. A total of 96 weaned rabbits were separated into four equal groups
      with three subgroups each. One group was given the basal diet and served as
      control, two groups were administered diets supplemented with oregano essential
      oil at levels of 100 and 200 mg/kg diet, whereas the remaining group was given a
      diet supplemented with alpha-tocopheryl acetate at 200 mg/kg. During the 42-day
      experimental period, body weight and feed intake were recorded weekly and the
      feed conversion ratio was calculated. Feeding the experimental diets to rabbits,
      performance parameters were not affected. Therefore, dietary oregano essential
      oil exerted no growth-promoting effect on rabbits. With increased supplementation
      of oregano essential oil, malondialdehyde values decreased in both raw and
      thermally treated muscles during refrigerated storage. This finding suggests that
      dietary oregano essential oil exerted a significant antioxidant effect. Dietary
      supplementation of oregano essential oil at the level of 200 mg/kg was more
      effective in delaying lipid oxidation compared with the level of 100 mg/kg, but
      inferior to dietary supplementation of 200 mg alpha-tocopheryl acetate per kg.
      This study indirectly provides evidence that antioxidant compounds occurring in
      oregano essential oil were absorbed by the rabbit and increased the antioxidative
      capacity of tissues.

PMID- 15264671
TI  - Digestibility of carbohydrates in growing pigs: a comparison between the T
      cannula and the steered ileo-caecal valve cannula.
AB  - We compared the determination of ileal and total tract digestibility of
      carbohydrates in five experimental diets using a double 5 x 5 Latin square design
      involving a total of 10 cannulated pigs; half of the pigs were equipped with a
      simple T-cannula and the other half with steered ileo-caecal valve (SICV)
      cannula. The diets consisted of nitrogen-free mixture and soya bean meal,
      sunflower meal, peas or rape seed cake diluted to about 180 g/kg DM protein with
      the nitrogen-free mixture. There was no significant difference in the
      digestibility values using the two types of cannulas with regard to organic
      matter, sugars (sum of glucose, fructose and sucrose), alpha-galactosides (sum of
      raffinose, stachyose and verbascose), starch, cellulose, total non-cellulosic
      polysaccharides (NCP) and insoluble NCP constituents. The digestibility values
      for the NCP residues arabinose and galactose, however, were estimated higher but
      with a lower variability with the SICV-cannula compared with the T-cannula. The
      type of cannula did no influence the estimation of the total tract digestibility
      for any of the major dietary constituents, but the total tract digestibility was
      slightly more variable when the pigs were equipped with the SICV-cannula compared
      with the T-cannula. There was no difference in the ileal digestibility of sugars,
      alpha-galactosides, cellulose and the NCP arabinose and uronic acids residues
      among the experimental diets, while the ileal digestibility of starch and the
      remaining NCP sugar residues varied between diets. The total tract digestibility
      was complete for sugars, alpha-galactosides and starch, whereas the digestibility
      of the cell wall constituents varied in accordance with the polymeric composition
      of the cell walls. It was concluded that ileal digesta samples from SICV-cannula
      are more homogenous than those from the T-cannula. In cases where the precision
      of each determination is crucial, the SICV-cannula should be the option.

PMID- 15264672
TI  - Agri-environmental grass hay: nutritive value and intake in comparison with hay
      from intensively managed grassland.
AB  - Chemical composition, digestibility, nutritive value and intake of hay from an
      agri-environmental management (EH) were compared with those from hay (Lolium
      perenne) from an intensive management (IH). IH was of low to moderate quality
      because of unfavourable weather conditions. EH was harvested mid-June of 2000
      (EH1) and 2001 (EH2) on the same sward that had not received mineral fertilizer
      for 10 years. The EH was characterized by a species-rich botanical composition.
      On average, it had lower contents of protein (32%), NDF (9%) and ash (35%), and a
      higher concentration of water-soluble carbohydrates (117%) than IH. Digestibility
      of dry and organic matter, determined with sheep, was not different between IH
      and EH and averaged 59 and 63%, respectively. Crude fibre and NDF digestibility
      were lower in EH (58 and 57%, respectively) than in IH (70 and 69%,
      respectively). Net energy value for lactation did not differ between IH and EH
      and amounted to 4.78 MJ per kg DM. True protein digested in the small intestine
      and rumen degraded protein balance were lower in EH (63 and -60 g per kg DM) than
      in IH (71 and -33 g per kg DM). Intake of hay was investigated in Holstein
      Friesian heifers and Belgian Blue double-muscled heifers (mean BW 280 +/- 22 kg
      and 269 +/- 21 kg, respectively), and in Belgian Blue non-lactating and non
      pregnant double-muscled cows (initial BW 642 +/- 82 kg), using a cross-over
      design. Hay was freely available. It was supplemented with 1 kg concentrate
      daily. Dry matter intake from hay was higher for EH than for IH in heifers (4%
      and 13%, respectively in Holstein-Friesian and Belgian Blue heifers) and in cows
      (22%). Hay from an agri-environmental management may be used for low-performing
      animals, as energy intake only exceeded maintenance requirements by 20 to 35%.
      Several characteristics of EH were different between years, such as dry matter
      digestibility, net energy value for lactation and fermentable organic matter
      content.

PMID- 15264673
TI  - The effects of lactic acid bacteria inoculants and formic acid on the formation
      of biogenic amines in grass silages.
AB  - Silages were prepared in six laboratory experiments from four direct-cut
      grassland swards and pure swards of perennial ryegrass and false oat with dry
      matter contents ranging between 180 and 325 g/kg. Grass was fermented at 22
      degrees C and silages were stored at the same temperature for 4 months. Untreated
      silages (negative control) and silages preserved with 3 g/kg of formic acid
      (positive control) were compared with silages inoculated with commercial strains
      of Lactobacillus plantarum, Lactobacillus buchneri and a mixed preparation
      Microsil. The inoculants were applied at a dose of 5.10(6) CFU/g of grass. Seven
      biogenic amines were extracted from silages with perchloric acid and determined
      as N-benzamides by micellar electrokinetic capillary chromatography. Common
      chemical quality parameters of silages were also determined. Tyramine, cadaverine
      and putrescine were the amines occurring at the highest concentration. As
      compared to untreated silages, formic acid was most effective to suppress
      formation of the main amines. Also the inoculants often decreased amine contents
      significantly (P < 0.05). The inoculants decreased levels of polyamine spermidine
      more efficiently than formic acid. Contents of histamine, tryptamine and
      polyamine spermine were very low, commonly below the detection limits.

PMID- 15264674
TI  - Effect of alfalfa meal in diets of laying quails on performance, egg quality and
      some serum parameters.
AB  - This study was conducted to investigate the effects of increasing levels of
      alfalfa meal in the diet of laying quails on egg production, feed consumption,
      feed efficiency, egg quality, egg yolk cholesterol and selected serum parameters.
      In this study, 192, 10-week old quails (Coturnix coturnix japonica) were evenly
      distributed to four groups with four replicates of 12 quails each. The control
      group was fed a basal diet containing 0% alfalfa meal and the remaining groups
      received 3, 6 or 9% alfalfa meal for 12 weeks. Live weight, feed consumption, and
      egg production were recorded and feed efficiency were calculated. Eggs were
      examined for interior and exterior quality and egg yolk cholesterol content. At
      the end of the experiment, blood samples were collected and sera were analysed
      for serum Ca, inorganic P (P(i)), Mg, triglycerides and total cholesterol. Any
      level of alfalfa meal had no effect on live weight, egg production, feed
      consumption, feed efficiency, egg weight, and egg yolk index. Six percent and 9%
      alfalfa meal increased specific gravity of whole egg and eggshell thickness as
      well as serum P(i) levels. Nine percent alfalfa meal reduced serum triglycerides,
      total cholesterol levels and egg yolk cholesterol content. The results of this
      experiment indicated that addition of 9% alfalfa meal into the laying quail diet
      may improve eggshell quality and reduced serum triglycerides and serum and egg
      yolk cholesterol without any adverse effect on performance.

PMID- 15264675
TI  - [Analysis of renal neoplasms in adult patients under 40].
AB  - OBJECTIVES: To analyze within our sample population the number of patients under
      40 receiving surgery as a result of renal neoplasm; to describe the
      characteristics of these patients and compare them with those of adult patients
      over 40. PATIENTS AND METHODS: We have revised the clinical history of the 379
      patients with renal neoplasm who have undergone surgery in our Service from
      January 1986 through June 2003. Patients were divided into two groups. Group I,
      formed by 36 subjects (9.5%) < or = 40. Group II includes 343 patients (90.5%)
      over 40. Data were included in a database created using the software programme
      Access and were subsequently analysed using the statistical package SPSS. A
      descriptive analysis was performed and life expectancy was calculated for both
      groups using the Kaplan-Meier survival curve. RESULTS: 7.3% of the total number
      of renal cell carcinomas included in our series occurs in patients of or under
      40. No significant differences have been observed as regards the distribution per
      sexes, laterality, size, incidental occurrence, clinical symptoms,
      anatomopathology, staging or surgical technique employed. However, we have
      observed differences as regards cancer-specific survival rate after 5 years,
      being 94.74% in the case of group I and 68.64% in group II (log-rank 0.0338).
      CONCLUSIONS: The number of patients < or = 40 undergoing surgery as a result of
      renal cell carcinoma in the sample under study matches other series already
      published. No statistically significant difference has been observed as regards
      staging among patients under and over 40. Differences do exist as regards cancer
      specific survival rate. In the case of our patients, irrespective of the age
      group to which they were ascribed, it is more common to diagnose a renal neoplasm
      incidentally than through the clinical manifestations.

PMID- 15264677
TI  - [Could the BCG vaccine prevent bladder cancer?].
AB  - In developed countries, the incidence of tuberculous is major, and the incidence
      of bladder cancer is minor. Above the base of the utility of the BCG in the
      prevention of the tuberculous and the use in the treatment and prevention of the
      recurrences of cancer, it's investigated the relation between the 2 pathology's.
      PATIENTS AND METHODS: We effected a study retrospective and prospective. It's
      revised the history's of 52 cases of bladder cancer, it's interview 100 persons,
      and interview medicals what to dedicate to treat patients whit tuberculous, above
      the existence before patient what had the 2 pathology's or before case vaccinate
      with BCG what to develop bladder cancer. It's a study effected in tree groups of
      patients, in a period of 14 year, between 1985-1999. RESULTS: First group: all
      the cases what development bladder of cancer none of them to vaccinate with BCG.
      Second group: all to vaccinate with BCG with prevention of lung tuberculous none
      of them development bladder of cancer in the course of mean of 32 year. Third
      group: none of the patients what to treat for tuberculous developed bladder of
      cancer. Never a medical interview observe case some what development the two
      pathology's, or patients what vaccinate with BCG what development bladder of
      cancer.

PMID- 15264676
TI  - [Experimental study of the expression of the bladder wall proteins in bladder
      outlet obstruction in the rabbit].
AB  - OBJECTIVES: To determine the relationship of the bladder wall levels of the
      contractile proteins: whole actin, beta-actin, alpha-sarcomeric-actina caldesmon
      and of the Heat Stress Protein HSP-70, with the partial bladder outlet
      obstruction. MATERIAL AND METHODS: It was carried out an experimental study on 43
      New-Zealand rabbits. These animals were divided into a control group and six
      experimental groups with partial bladder outlet obstruction induced by an
      incomplete tie around the urethra. The experimental groups were defined according
      the day when the animals were sacrified: at 24 hours, 7 days, 15 days, 1 month, 3
      months and 6 months of the obstruction. It was determined in all animals the
      muscular bladder wall concentration of whole actin, beta-actin, alpha-sarcomeric
      actin, caldesmon and HSP-70 protein, according to Western Blotting technique. The
      results were analyzed by means of ANOVA, using the Scheffe post hoc method.
      RESULTS: The bladder weight of the obstructed animals increased significantly in
      two stages: until the day 15 and between the day 15 and the end of the study,
      corresponding to theoretical phases of initial hypertrophy and compensation. The
      level of whole actin showed a significant decrease at the beginning of
      compensation phase, while the beta-actin level increased in the phase of initial
      hypertrophy and the alpha-sarcomeric-actin level increased at the end of the
      compensation phase, while the caldesmon and the HSP-70 made it at the end of the
      initial hypertrophy phase. CONCLUSIONS: Analysing our data we conclued that the
      determination of the caldesmon levels is the marker that better adjusts to the
      changes associated with partial bladder outlet obstruction in the rabbit.

PMID- 15264678
TI  - [Natural history of localized prostate cancer. Preliminary data on progression
      and mortality].
AB  - OBJECTIVE: To address the effect of therapy options and other factors on the
      natural history of localized prostate cancer (PCa). METHODS: Men with diagnosed
      clinically localized PCa who underwent radical prostatectomy (RP), radiotherapy
      (RT) or watchful waiting (WW). Rates of biochemical progression (BQP) and
      clinical progression (CLP) were calculated. The effects of therapy, initial PSA,
      presence of palpable tumor and Gleason score were assessed with Kaplan-Meier
      analysis and log-rank test. Similar methods were used to study overall and
      disease-specific survival. RESULTS: A total of 228 patients were studied (135
      underwent RP, 46 RT, and 47 WW). Median followup time was 2.5 years. Forty
      patients presented with BQP. The probability of being free from BQP after 2 and 5
      years was 76.8% and 57.9% respectively for the whole population, 70.9% and 57.6%
      for RP patients, 100% and 100% for RT, and 87.1% and 47.2% for WW (p = 0.031).
      Nineteen patients presented with CLP, with no significant differences with regard
      to therapy option. A poorly differentiated Gleason score favoured the probability
      of presenting with CLP (p = 0.022) and shift to metastatic disease (p < 0.001).
      No cancer-specific mortality was recorded in the studied population. CONCLUSIONS:
      Short and medium-term prognosis is excellent for localized prostate cancer in
      terms of survival. Nevertheless, some patients show a higher risk of progressing
      to metastatic disease (poorly differentiated Gleason score).

PMID- 15264679
TI  - [Usefulness and necessity of the andrologist in assisted reproductions units].
AB  - In this issue we make a review of our experience in the management of the sterile
      men: protocols used for the study of men's sterility, causes and specific
      treatments, surgical recovery of spermatozoa and screening before IVF or IVF
      ICSI. We concluded that with an adequate protocol, it's possible to establish the
      aetiology of men's infertility in a 78.8% of the cases and it's also possible to
      initiate a specific treatment in almost a 47.8% of men. Results of specific
      treatment, with a previous selection of patients, could be better than those of
      assisted reproduction techniques. Best results are obtained in cases of vaso
      vasostomy (vasectomy reversal) and obstruction of ejaculatory duct. It's also
      needed a study of genetics causes and bad prognostic circumstances in those men
      whose partner is going on with an IVF or IVF-ICSI cycle.

PMID- 15264680
TI  - [Pure primary prostate transitional cell carcinoma. A review of our series].
AB  - Primary prostate transitional cell carcinoma is a very uncommon tumor, that
      represents about 1% of all prostate tumours. In our institution, only six
      patients have been diagnosed with pure transitional cell prostate carcinoma until
      2002. Bladder origin of the neplasic was ruled out in all cases. We report a
      study about the progression and survival of prostate transitional cell carcinoma.
      These prostatic tumours carry a poor prognostic (median survival is 4.6 months)
      with a strong tendency to metastatic spread. Therefore, we suggest a radical
      prostatectomy (without cystectomy) when it rules out bladder origin tumour.

PMID- 15264681
TI  - [Usefulness of serum markers in renal cell carcinoma].
AB  - OBJECTIVES: To select a group of useful serum markers in renal cell carcinoma
      (RCC) with investigational purpose in future. MATERIAL AND METHODS: Periodic
      determination in serum of 21 RCC patients of the following markers: EGR, RPC,
      hemogram and leucocyte differential count (LDC), standard biochemist parameters,
      beta-2 microglobuline, CEA, CA 12.5, CA 50, CA 15.3, ferritin, interleukin-6,
      serum interleukin-2 receptor, TNF-alpha and TPSA. RESULTS: Different elements
      within the LDC had relations with the presence of symptoms/signs, tumour size,
      pathological stage and disease progression. There was a significant increase of
      beta-2 microglobuline and sIL-2 receptor when disease progressed, as well as a
      similar statistical trend with RPC and alkaline phosphatases. Beta-2
      microglobuline and sIL-2 receptor also decreased after treatment of the disease
      progression. CONCLUSIONS: We will keep analysing hemogram, LDC and standard
      byochemics, RPC, ferritin, beta-2 microglobuline and sIL-2 receptor only with
      investigational purposes, obviating the determination of the rest of the tested
      markers.

PMID- 15264682
TI  - [Priapism as an initial presentation of chronic myeloid leukaemia].
AB  - We report the case of a 29 years old patient who presented, in the last three
      moths, four episodes of priapism without any other symptoms and any previous
      traumatism. An hemogram reveled that the repeted episodes of priapism were caused
      by a chronic myeloid leukaemia.

PMID- 15264683
TI  - [Foreign body simulating kidney tumour].
AB  - A six cm kidney tumour is found in a prostate control ultrasonography, in a 70
      aged men. A chirurgical remove is indicated the tumour presented a very few
      separation of the kidney. The kidney was only compressed by the mass which
      contained a chirurgical gauze inside it from a previous surgery 35 years before.

PMID- 15264684
TI  - [Primary renal lymphoma in a patient with IgM monoclonal gammapathy].
AB  - Reports on primary renal lymphoma are scarce in the urological literature, the
      most part of them are secondary on a lymphomatous infiltration of the kidneys. We
      report the case of a 77 year old man with an incidental mass on the kidney. After
      radiological studies (CT), we practise nephrectomy with a pathological result of
      a non-Hodgking B primary lymphoma. The patient present a IgM monoclonal
      gammapathy who need complementary treatment with chemotherapy. A literature
      review on currently recommended diagnostic and treatment practices in presented.

PMID- 15264685
TI  - [Extracorporeal shock wave lithotripsy of urolithiasis in patients with urinary
      diversion].
AB  - We evaluate the efficacy of ESWL in the management of calculi in patients with
      urinary diversion. We treated 5 patients who suffered from urinary lithiasis
      after urinary diversion post cistectomy. We managed the patients with
      extracorporeal shock wave lithotripsy in monotherapy with a Siemens Lithostar
      Modularis device. Mean stone size (long axis) was 1.95 cm (range 1 to 3.5 cm).
      The mean shockwave number per session was 2.6 per patient. Stone free result was
      100%. We conclude that ESWL technique can provide acceptable results in patients
      with urinary diversion and can be used as first choice treatment in these type of
      patients due to its minimal morbidity and excellent results, equivalent to those
      achieved in patients without urinary diversion.

PMID- 15264686
TI  - [Berdon syndrome (megacystis, microcolon, intestinal hypoperistalsis). Report of
      our cases].
AB  - Berdon syndrome is a rare congenital malformation that consists in megacystis and
      severe intestinal malformations that condition the prognosis in most of the
      cases. We report the three cases diagnosticated between 1976-2003. Diagnosis,
      therapeutics aspects and evolution are discussed.

PMID- 15264687
TI  - [Thoracic renal ectopia].

PMID- 15264688
TI  - [Complete sustitution of urinary tract with ileum due to a transitional tumor].

PMID- 15264689
TI  - [Renal metastasis of colon carcinoma].

PMID- 15264690
TI  - [Genetic background of epilepsies].
AB  - In this article we review epilepsies with monogenic inheritance. Most of these
      diseases are caused by abnormal function of ligand- and voltage gated ion
      channels caused by a genetic defect, therefore belonging to the channelopathies.
      From the inherited epilepsies the genetics of the autosomal dominant partial
      epilepsies is clarified the best. Mutations of the nicotinic acetylcholine
      receptor subunits are found in familial nocturnal frontal lobe epilepsy, while
      defects in the voltage gated potassium channels (KCNQ2 and KCNQ3) have been
      identified in benign familial neonatal convulsions. Familial temporolateral
      epilepsy was associated with mutations of a tumor suppressor gene. From the
      generalized epilepsies, the syndrome of generalized epilepsy with febrile
      seizures plus (GEFS+) can be caused by mutations of the sodium channel subunits
      and of the GABAA receptor subunits. These important results would probably lead
      to new findings in the genetics of the more common forms of idiopathic
      generalized epilepsies, which have presumed polygenic origin. Although without
      definite conclusions, sodium channel and GABA receptor dysfunction is presumed.
      The accumulated knowledge about channelopathies enables insight to the cellular
      mechanism of epileptogenesis as well.

PMID- 15264691
TI  - [Diagnosis of epilepsy].
AB  - 0.5-1% of the population suffers from epilepsy, while another 5% undergoes
      diagnostic evaluations due to the possibility of epilepsy. In the case of
      suspected epileptic seizures we face the following questions: Is it an epileptic
      seizure? The main and most frequent differential-diagnostic problems are the
      psychogenic non-epileptic seizures ("pseudo-seizures") and the convulsive
      syncope, which is often caused by heart disorders. Is it epilepsy? After an
      unprovoked seizure, the information on recurrence risk is an important question.
      The reoccurrence is more possible if a known etiological factor is present or the
      EEG shows epileptiform discharges. After an isolated epileptic seizure, the EEG
      is specific to epilepsy in 30-50% of cases. The EEG should take place within 24
      hours postictally. If the EEG shows no epileptiform potentials, a sleep-EEG is
      required. What is the cause of seizures? Hippocampal sclerosis, benign tumors,
      and malformations of the cortical development are the most frequent causes of the
      focal epilepsy. Three potentially life-threatening conditions may cause chronic
      epilepsy: vascular malformations, tumors, and neuroinfections. The diagnosis in
      theses cases can usually be achieved by MRI, therefore, MRI is obligatory in all
      epilepsies starting in adulthood. The presence of epileptogenic lesion has a
      prognostic significance in treatment. If the MRI shows a circumscribed lesion
      then the pharmacological treatment will likely to be unsuccessful, while surgery
      may result in seizure freedom. The new and quantitative MRI techniques, such as
      volumetry, T2-relaxometry, MR-spectroscopy, and functional MRI play a growing
      role in the epilepsy diagnosis.

PMID- 15264692
TI  - [Questions of epileptogenesis and prevention in symptomatic epilepsies].
AB  - Symptomatic epilepsies usually report themselves after a longer period of time
      after brain injury, after the so-called latent period. During this period
      progressive functional and structural changes occur which finally cause an
      increased excitatory condition. The process of epileptogenesis may be examined in
      animal models, such as in the kindling, status epilepticus, hypoxicischaemic
      models. Data gained from such sources support the hypothesis that the first
      injury results in a lower seizure threshold, but genetical and environmental
      factors also contribute to the development of epilepsy and most probably further
      insults may be needed. The development of epilepsy can be traced back to several
      reasons. In spite of this, the latent period provides opportunity for the
      prevention of epilepsy or for the influence of epileptogenesis in such a manner
      that later treatment can become more successful. Prevention should be an aim in
      clinical practice, as well. Medication used presently are more like to have
      anticonvulsive properties and their antiepileptogenic effect is questionable. Due
      to this fact, development of new drugs is necessary with new theoretical
      background. The most important influence on the incidence of epilepsy in recent
      years has been provided by the improvement in neonatal care. This highlights the
      fact that such optimal medical care should be provided in the acute period of
      brain injury which can terminate or lessen the risk of epilepsy.

PMID- 15264693
TI  - [Pharmacotherapy of epilepsy].
AB  - Antiepileptic drug treatment is essential and provides excellent therapeutic
      effects in more than the two-third of the epileptic patients. The antiepileptic
      drugs influence the chronic hyperexcitability of the brain developed during the
      epileptogenesis. As an effect, it decreases the excitability and/or increases the
      inhibition of the pathological cells, which prevents the precipitation of the
      epileptic seizure (anticonvulsive effect). The anticonvulsive effect comes into
      operation by the influence of the transport of one ore more ion-channels. The
      anticonvulsive effect is only symptomatic and it doesn't cure the disorder. The
      drug selection is based on the knowledge of the therapeutic markers and the
      effectiveness of the drug to be used. This can occur on the basis of the action
      of the drug or in syndrome-specific way. The pharmacokinetic properties of the
      drugs determine how they can be used in the practice. The drug interactions can
      take place in several levels. Among them, the change of the metabolism is the
      most important. Acute dose-dependent side effects, organ-specific chronic
      interactions and idiosyncratic reactions must be taken into consideration during
      the use of antiepileptic drugs. The patient's individual aspects must be
      considerably taken into account during the treatment. There are other medical
      areas that can benefit from the antiepileptic drugs. Among them, the most
      important diseases are: restless legs syndrome, neuropathic pain, trigeminal
      neuralgia, essential tremor, bulimia and bipolar disorders. There are other
      pharmacological (adrenocorticotropic hormone, immunoglobulins, neurosteroids) and
      dietary methods, which may be effective at certain epileptic syndromes. The
      principles of the pharmacotherapy have been changing continuously during the past
      decades and since. New drugs have been introduced into the marketing and new
      expectations are coming into the limelight concerning the treatment. As a
      consequence this will bring on the modification of antiepileptic drug therapeutic
      habits.

PMID- 15264694
TI  - [Surgical treatment of epilepsy].
AB  - In this article the possibilities, indications, methods and results of surgery in
      epilepsy are summarized in general with the Hungarian experience emphasized.
      Surgery may provide effective treatment in about 5-10% of the epileptic
      population. Surgical solution nowadays became an essential treatment in medial
      temporal epilepsy, if hippocampal sclerosis or other lesion is present, in
      therapy resistant lesional extratemporal epilepsies and in catastrophic childhood
      epilepsies if the epileptic disorder is restricted to one hemisphere (Rasmussen
      syndrome, hemimegalencephaly, Sturge-Weber disease and posttraumatic or
      postencephalitic hemispherial epilepsies). The algorithms of the presurgical
      evaluation and the current methods for study the pacemaker area, forbidden zones,
      and hemispherial functions are treated. The currently used type and techniques of
      surgery, such as lesionectomy, temporal lobe resections, hemispherotomy,
      callosotomy, multiple subpial transsections and their indications are described.
      The newest surgical approaches, as deep brain stimulation, vagal nerve
      stimulation, and irradiation techniques are also briefly touched. Lastly, we deal
      with prognostical factors of the surgical outcome, reasons of surgical failures
      and complications. In a brief chapter the importance of postsurgical
      rehabilitation is emphasized.

PMID- 15264695
TI  - [Psychosocial conditions of adult epileptic patients in Hungary].
AB  - Authors analyze the possible connections among psychosocial, more important
      epileptological and social conditions in the population of the Hungarian Epilepsy
      Database. The inclusion criteria were the presence of repeated epileptic
      seizures, the strict diagnosis of epilepsy and at least three registered control
      visits. Four hundred and fifty 30 or more years old patients fulfilled the
      criteria. Based on the answers to four questions in the database considering some
      conditions potentially modifying the way of life the patients were scored and
      distributed into 3 subgroups (good, average and bad) concerning their
      psychosocial conditions. In contrast to previous expectations they found that the
      type of epilepsy does not influence the attainable psychosocial conditions.
      Presence of generalized tonic-clonic or complex partial seizure did not exhibit
      influence either. Analysis of the seizure frequency showed that generalized
      convulsions, if occurred rarely were accompanied by good psychosocial level and
      if occurred frequently they were accompanied by a less acceptable level.
      Psychopathological symptoms independently from their nature and evidenced brain
      lesion as etiology also made the psychosocial conditions worse. No difference was
      found concerning the gender of the population. It contradicts the hypothesis that
      epilepsy has a greater impact on females. Psychosocial conditions are better in
      patients with higher education and living in pairs. Based on the study authors
      support the statements of the literature emphasizing that for achieving the best
      quality of life and psychosocial level an appropriate medical care is not enough.
      They need also the relative highest level of education and a stable partnership.

PMID- 15264696
TI  - A female infant with hypotonia and cardiomegaly.

PMID- 15264697
TI  - Arterial switch operation for transposition of the great arteries: an encouraging
      result.

PMID- 15264698
TI  - Kawasaki disease.

PMID- 15264699
TI  - Surveillance of Kawasaki disease in Taiwan and review of the literature.
AB  - BACKGROUND: Kawasaki disease affects mainly children younger than five years,
      leading to coronary artery lesions, even to life-threatening myocardial
      infarctions. Since 1976, Kawasaki disease has occurred in thousands of children
      in Taiwan; some of them died. METHODS: Questionnaire forms for the survey of
      epidemiological features of Kawasaki disease were designed and sent to the
      hospitals of 100 or more beds in Taiwan, in 1987, 1992, 1994, and 2001, for
      retrospective reviews of their patients with Kawasaki disease encountered during
      1976-2000. A school-based mass survey, on the prevalence of children with history
      of Kawasaki disease was conducted every year from 1990 to 2000. RESULTS: Since
      1976, the number of Kawasaki disease patients increased, totaling to 8,267
      patients in 2000. The ratio of the incidence increased by 1.15 times annually
      (Poisson regression), reaching the highest incidence of 54.9 per 100,000 children
      <5 years of age in 1998. Of them, 85.1% were under 5 years of age. The male-to
      female ratio was 1.6. Coronary artery lesions were noted during acute, subacute
      and convalescent stages in 25.8% of the patients. The fatality rate decreased
      from 0.4% to 0.06%. There was no student with history of Kawasaki disease among
      students surveyed in 1990. Subsequent school surveys showed the prevalence was
      24.6 in 1991, 74.6 in 1996, then reached to 103.9 per 100,000 school children in
      2000, with an annual increase of 1.24 times (Poisson regression). CONCLUSIONS: In
      Taiwan, Kawasaki disease, first diagnosed in 1976, continued to occur with
      several outbreaks reaching to a peak incidence of 54.9 per 100,000 population
      less than 5 years of age in 1998. Epidemiological features of Kawasaki disease in
      Taiwan were similar to the Japanese experiences and the incidence was, next only
      to Japan, the second highest in the world.

PMID- 15264700
TI  - Pulmonary function assessment in patients with spinal muscular atrophy type II
      and type III.
AB  - In this study, we used a spirometer to measure pulmonary function of 48 patients
      (4.3 to 34 years old), with type II and type III spinal muscular atrophy (SMA)
      and compared our findings according to the two SMA types, sex, functional grade,
      and degree of scoliosis. SMA patients were stratified into three groups based on
      severity and the age at which the symptoms began: type I, type II, and type III
      SMA patients were also classified into four functional grades depending upon
      whether they were able to 1) sit with support, 2) sit independently, 3) walk with
      assistance, or 4) walk independently. A restrictive pattern was found in all SMA
      patients who were found to have impaired lung function. The highest functional
      group had normal or nearly normal pulmonary functions. The lowest functional
      group, however, were found to have the worst pulmonary functions. Patients with
      type III SMA had better lung function than type II. We found a significant
      inverse relationship between pulmonary function and scoliosis, but no significant
      difference in pulmonary functioning with respect to gender. As the functional
      grade decreases, chest care needs to be intensified to prevent respiratory tract
      infections.

PMID- 15264701
TI  - Arterial switch operation for transposition of the great arteries: experience
      from 2000-2002 in Taiwan.
AB  - Arterial switch operation (ASO) is considered the procedure of choice for
      transposition of great arteries (TGA). The results and long-term prognosis
      improved with recent advances in perioperative management. We herein analyze the
      clinical outcome of patients undergoing ASO at our institution during the past 3
      years. From 2000 to 2002, 44 patients (30 male and 14 female) of TGA received
      ASO. Age at operation varied from 4 days to 6.6 years (median 14 days) with body
      weight ranged from 2.25 kg to 18.1 kg (median 3.3 kg). Palliative procedure prior
      to ASO was performed in 8 patients (18.8%). Normal coronary artery pattern was
      found in 28 patients (63.6%). The early mortality was 11% (5/44). Only associated
      ventricular septal defect (VSD) was a significant predictor for operative
      mortality (p=0.012). With a follow-up ranged from 11 to 44 months, the gradient
      of neo-pulmonary artery stenosis was 16.5 +/- 18.2 mmHg. Four patients (10%)
      received balloon dilatation and the other three (7.7%) underwent reoperation. The
      gradient of neo-aortic stenosis was 16.5 +/- 18.2 mmHg that needed to be dilated
      in three patients (7.7%). The probability free from reintervention was 73% at the
      3rd postoperative year. One patient had moderate degree of pulmonary valve
      regurgitation and six had moderate neo-aortic valve regurgitation. In conclusion,
      the ASO can be performed in infants with satisfactory results, even in those with
      a body weight less than 2.5 kg. Only associated VSD was shown to be a risk
      factor.

PMID- 15264702
TI  - Growth curves of aboriginal children in Taiwan.
AB  - The aims of the study were to establish individual percentile charts of the body
      height, weight and body mass index (BMI) for Taiwanese aboriginal children, aged
      from 7-18 years old, and to compare the growth data of aboriginal children to the
      data of children in Taiwan and Fukien areas collected in 2002. In total 6,720
      aboriginal boys and 6,414 aboriginal girls were included in this study. Cole's
      LMS method was used to draw the smoothed growth charts. The results revealed that
      the aboriginal girls were slightly taller and heavier than the aboriginal boys
      during most of childhood but the aboriginal boys surpassed the aboriginal girls
      beginning at age 13. Growth velocity slowed down in the aboriginal girls at age
      11 and in the aboriginal boys at age 14. The aboriginal boys rapidly gained
      weight during 7-18 years of age. The weight curves of aboriginal boys and girls
      had similar patterns before the age of 16. This increase in weight continued in
      the aboriginal boys', but it plateaued for aboriginal girls around 16 to 17 years
      of age and even declined at the age 18 in the 97th percentile. When comparing
      this data to the data from 2002, the aboriginal children demonstrated similar
      growth patterns as the nationwide children in the 15th, 50th, and 85th
      percentiles of body height, weight, and BMI respectively. The one exception was
      the BMI of the aboriginal boys. It was increasingly higher than the nationwide
      correspondents during the late teenage years. The aboriginal girls had slightly
      higher BMI than the nationwide girls at every age. Based on these results,
      developing programs aimed at preventing aboriginal boys from becoming overweight
      before they reach their late teenage years is suggested to administrators of
      health and education services.

PMID- 15264703
TI  - Risk factors of mortality in meconium aspiration syndrome: review of 314 cases.
AB  - Meconium aspiration syndrome (MAS) is a common severe respiratory disease in full
      term infants. To investigate the risk factors for mortality of MAS, a
      retrospective chart-review study of MAS was conducted from 1995 to 2001. All
      cases of MAS were included except cases of cyanotic congenital heart disease or
      congenital fetal anomaly. Prenatal, perinatal and postnatal risk factors of
      mortality were recorded. The risk factors were compared between surviving and
      deceased cases. There were 314 cases of MAS during the seven years. Total
      mortality rate was 4.8% (15/314); this did not change significantly during these
      years. Risk factors of mortality by univariate analysis were: outborn babies,
      resuscitation before admission, first born baby, low pH, high oxygen index (OI),
      high alveolar-arterial oxygen tension gradient (AaDO2) at admission, high OI and
      AaDO2 at 2 hours after admission, shock, pneumothorax, asphyxia, pulmonary
      hemorrhage, persistent pulmonary hypertension of newborn (PPHN), and renal
      failure. Logistic regression analysis showed asphyxia, pneumothorax and PPHN are
      the most important risk factors of mortality in MAS. How to diminish these events
      is the key point for reducing the mortality rate of MAS.

PMID- 15264704
TI  - Extravasation of calcium gluconate concomitant with osteomyelitis in a neonate.
AB  - Extravasation of calcium gluconate is not an uncommon complication in neonatal
      units, which may result in skin and soft tissue inflammation, injury and even
      infection. We report an 11-day-old preterm infant who developed osteomyelitis at
      an infiltrated intravenous site through which calcium gluconate was infused. The
      patient was initially treated conservatively as a simple calcium-infiltrate.
      Clinical condition deteriorated until proper antibiotic treatment was given. We
      exclude other possible causes and assume that calcium-infiltrate had an important
      role in the pathogenesis. We conclude that osteomyelitis should be considered in
      a patient with calcium extravasation whose soft tissue inflammation does not
      improve as expected. Furthermore, using a diluted calcium solution and checking
      the insertion site frequently in order to identify extravasation earlier would
      prevent the complication.

PMID- 15264705
TI  - Geotrichum capitatum fungemia with skin lesions similar to varicella in a patient
      with acute lymphocytic leukemia.
AB  - Varicella-zoster virus (VZV) can cause increased morbidity and mortality in
      immunocompromised persons. Varicella lesions (macules, papules and vesicles)
      often appear first on the scalp, face or trunk. We report the case of a leukemic
      patient who developed multiple maculopapular rashes with central vesicles after
      chemotherapy. The skin lesions were first noted on the scalp, face and then trunk
      and extremities. These manifestations were similar to those caused by VZV. Both
      blood culture and skin vesicle fluid culture yielded Geotrichum capitatum, which
      is a thermotolerant, yeast-like fungus that forms on culture cream-colored
      wrinkled colonies. Serology study and throat swab culture for VZV were negative.
      This case raises the possibility that fungal infection can manifest chickenpox
      like skin lesions in immunocompromised patients.

PMID- 15264706
TI  - Radiofrequency catheter ablation of idiopathic left ventricular tachycardia in a
      child.
AB  - Ventricular tachycardia occurring in apparently normal heart is rare in children.
      A 9-year-old boy presented with recurrent palpitations and syncope was found to
      have idiopathic ventricular tachycardia with a right bundle branch block
      morphology and left axis deviation. Pace mapping and activation mapping were used
      to localize the site of ventricular tachycardia origin. Radiofrequency catheter
      ablation successfully abolished this arrhythmia at a site of the midportion of
      the inferoseptal region of the left ventricle. This boy was free of tachycardia
      over follow-up of 2 years.

PMID- 15264707
TI  - Diffuse xanthogranulomatous pyelonephritis and staghorn calculus: report of one
      case.
AB  - Xanthogranulomatous pyelonephritis and staghorn calculus are rare in children. In
      this report, we describe a Chinese boy without history of urinary tract infection
      who developed insidious onset of left flank pain. Urine culture showed Proteus
      mirabilis infection. Sonography and computed tomography of the abdomen showed
      typical picture of xanthogranulomatous pyelonephritis and staghorn calculus.
      Photomicrography showed characteristic lipid-laden macrophage aggregates. After
      nephrectomy, he was symptom-free. In conclusion, xanthogranulomatous
      pyelonephritis should be considered in afebrile children with flank pain and
      staghorn calculus.

PMID- 15264708
TI  - Hypopituitarism associated with neurofibromatosis type 1: report of one case.
AB  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder with a wide
      range of clinical manifestations. Hydrocephalus unrelated to brain tumors is rare
      in neurofibromatosis type 1. A 16-year-and-6-month-old girl with primary
      amenorrhea was found to have hydrocephalus associated with neurofibromatosis type
      1. After endocrine and brain imaging study, the cause of primary amenorrhea was
      proven to be hypopituitarism due to hydrocephalus. She entered puberty soon after
      relieving the hydrocephalus with a ventriculoperitoneal shunt. However, arrest of
      puberty was noted three months later. Therefore estrogen replacement therapy was
      given. Early detection of hydrocephalus was difficult in this patient. From the
      experience of our case, MRI study of brain is indicated in patient with
      neurofibromatosis type 1 and endocrine dysfunction.

PMID- 15264709
TI  - Early cerebral images of Alexander disease: report of one case.
AB  - Alexander disease is a neurodegenerative disorder characterized pathologically by
      demyelination and accumulation of eosinophilic hyaline bodies (Rosenthal fibers)
      within astrocytes. Demonstration of Rosenthal fibers on histological examination
      is considered a prerequisite for a definitive diagnosis. However, the CT and MRI
      scans may be highly suggestive of the disorder. We describe a patient who
      presented with subtle seizures at the age of 4 months. On examination, he was
      floppy with evident head lag. There was no visual following or social smiling. At
      that time, the brain MRI showed abnormal findings, with more white matter
      involvement and a characteristic periventricular rim. A diagnosis of Alexander
      disease was not made until he was one year old, when a repeated MRI showed the
      full-blown pictures typically seen in Alexander disease. The images fulfilled the
      diagnostic criteria proposed by van der Knaap in 2001. The early brain MRI
      findings in Alexander disease can be very characteristic and greatly different
      from those in the late stage.

PMID- 15264710
TI  - The association between delirium and cognitive decline: a review of the empirical
      literature.
AB  - Delirium is a common neurobehavioral syndrome that occurs across health care
      settings which is associated with adverse outcomes, including death. There are
      limited data on long-term cognitive outcomes following delirium. This report
      reviews the literature regarding relationships between delirium and cognitive
      impairment. Psych Info and Medline searches and investigation of secondary
      references for all English language articles on delirium and subsequent cognitive
      impairment were carried out. Nine papers met inclusion criteria and documented
      cognitive impairment in patients following delirium. Four papers reported greater
      cognitive impairment among patients with delirium than matched controls. Four
      papers reported higher incidence of dementia in patients with a history of
      delirium. One study found 1 of 3 survivors of critical illness with delirium
      developed cognitive impairment. The evidence suggests a relationship between
      delirium and cognitive impairment, although significant questions remain
      regarding the nature of this association. Additional research on delirium-related
      effects on long-term cognitive outcome is needed.

PMID- 15264711
TI  - The role of cognitive deficits in the development of eating disorders.
AB  - Eating disorders (ED), including anorexia and bulimia nervosa, are chronic
      illnesses with periods of symptom exacerbation and remission. Because symptoms
      are usually present from 6 to 24 months before a diagnosis is made, aetiological
      agents are believed to be active well before symptoms appear. It is proposed that
      neuropsychological deficits in various cognitive domains preexist and underlie
      the aetiology of ED. This paper provides a comprehensive review of the literature
      relevant to neuropsychological deficits in ED patients and explores the
      relationship between cognitive deficits, psychosocial development, and the
      development of ED. Although the role of neuropsychological deficits in the
      evolution of ED requires further research, the proposed association has
      significant implications for clinical practice.

PMID- 15264712
TI  - Clinical perspectives on neurobiological effects of psychological trauma.
AB  - Physical trauma to the brain has always been known to affect brain functions and
      subsequent neurobiological development. Research primarily since the early 1990s
      has shown that psychological trauma can have detrimental effects on brain
      function that are not only lasting but that may alter patterns of subsequent
      neurodevelopment, particularly in children although developmental effects may be
      seen in adults as well. Childhood trauma produces a diverse range of symptoms and
      defining the brain's response to trauma and the factors that mediate the body's
      stress response systems is at the forefront of scientific investigation. This
      paper reviews the current evidence relating psychological trauma to anatomical
      and functional changes in the brain and discusses the need for accurate diagnosis
      and treatment to minimize such effects and to recognize their existence in
      developing treatment programs.

PMID- 15264713
TI  - Sampling and evaluation of white spot syndrome virus in commercially important
      Atlantic penaeid shrimp stocks.
AB  - In 1997, white spot syndrome virus (WSSV) was discovered in shrimp culture
      facilities in South Carolina, USA. This disease was known to cause devastating
      mortalities in cultured populations in Southeast Asia and prompted concern for
      the health of wild populations in the USA. Our study surveyed wild shrimp
      populations for the presence of WSSV by utilizing molecular diagnostics and
      bioassay techniques. A total of 1150 individuals (586 Litopenaeus setiferus, 477
      Farfantepenaeus aztecus and 87 F. dourarum) were examined for the presence of
      WSSV DNA by PCR. A total of 32 individuals tested positive and were used in a
      bioassay to examine the transmission of disease to healthy individuals of the
      culture species L. vannamei. DNA sequencing of PCR products from a positive
      individual confirmed that the positive individuals carried WSSV DNA. Significant
      mortalities were seen in test shrimp injected with tissue extracts from heavily
      infected wild shrimp. These data confirm the existence of WSSV in wild shrimp
      stocks along the Atlantic Coast and that the virus can cause mortalities in
      cultured stocks.

PMID- 15264714
TI  - Susceptibility of the Australian freshwater crayfish Cherax destructor albidus to
      white spot syndrome virus (WSSV).
AB  - Cherax destructor occurs naturally and/or is farmed in all Australian mainland
      states and territories and is of major cultural, economical and conservation
      significance. The aim of this study was to determine susceptibility of the
      commercially important subspecies C. destructor albidus to white spot syndrome
      virus (WSSV), a hazard to crustaceans and currently considered to be exotic to
      Australia. In challenge tests by intramuscular injection, C. destructor albidus
      displayed a similar level of susceptibility to white spot disease (WSD) as
      Penaeus monodon (i.e. 100% mortality in 3 d). In one oral challenge test where C.
      destructor albidus was subjected to significant temperature stress, over 50% died
      of severe WSD within 14 d post challenge. All dead and moribund crayfish
      displayed histopathological lesions typical for WSD and gave positive results for
      WSSV in DNA dot blot hybridization tests. Survivors to 30 d (n = 3) showed no
      lesions and gave negative dot blot test results. In a second oral challenge test
      without temperature stress, mortality was delayed but reached 75% by 30 d.
      However, no typical WSD lesions were observed in the dead, dying or surviving
      crayfish and dot blot test results were negative. The results suggested that C.
      destructor albidus would be less susceptible than P. monodon to WSSV exposure via
      natural routes of infection in farms and in the wild. This information may be
      useful for disease import risk analysis for WSSV.

PMID- 15264715
TI  - Quantitative real-time RT-PCR demonstrates that handling stress can lead to rapid
      increases of gill-associated virus (GAV) infection levels in Penaeus monodon.
AB  - Gill-associated virus (GAV) of the black tiger prawn Penaeus monodon has been
      implicated as a cause of periodic production losses in Australia since 1996. We
      report here the development of a real-time quantitative RT-PCR (qRT-PCR) for GAV.
      A dilution series of in vitro transcribed RNA was used to determine the
      sensitivity limit of the qRT-PCR and as a standard for GAV quantification. A
      linear relationship between cycle threshold (Ct) values and input RNA was
      obtained over a wide concentration range between 4.86 x 10(9) and 0.5 template
      copies per reaction, the latter being the test detection limit. The qRT-PCR was
      used to follow the progression of GAV levels in a group of 15 adult male P.
      monodon with chronic GAV infections that were super-infected by intramuscular
      injection of an inoculum containing high levels of GAV. By Day 9 post-injection,
      cumulative mortalities reached 100% (15/15) in the GAV-injected prawns and 40%
      (2/5) in placebo-injected prawns. Spermatophores were collected at the beginning,
      and together with other tissues, at the end of the trial. Prawns were also bled
      at regular intervals to collect circulating haemocytes. The qRT-PCR revealed that
      GAV loads increased significantly in haemocytes collected from both the control
      and super-infected prawns (p = 0.010). This increase was significantly higher in
      the super-infected prawns (p = 0.047). The rapid increase in GAV levels in super
      infected P. monodon was expected. However, the increase in the control prawns was
      not, and indicates that repetitive bleeding and handling stress can stimulate GAV
      proliferation in chronically infected P. monodon.

PMID- 15264716
TI  - Viral gametocytic hypertrophy caused by a papova-like virus infection in the
      Pacific oyster Crassostrea gigas in Korea.
AB  - During a routine survey of the Pacific oyster Crassostrea gigas in Tongyoung
      (previously Chungmu) on the southern coast of Korea, basophilic inclusions were
      observed in the gonadal tissues. They were detected from March to May at a
      prevalence rate of 3.3 to 7.1%. The inclusion bodies were Feulgen-positive and
      stained orange-red with phloxine tartrazine. Electron microscopic observation
      revealed non-enveloped, icosahedral particles 40 to 45 nm in diameter. These
      morphological characteristics resemble those of papova virus-like inclusions
      previously described from Pacific and eastern (American) oysters C. virginica in
      North America. Although many mitochondrial bodies and intact sperm cells were
      observed around the inclusion body, no host reaction, such as hemocytic
      infiltration, was detected.

PMID- 15264717
TI  - Susceptibility of captive adult winter-run Chinook salmon Oncorhynchus
      tshawytscha to waterborne exposures with infectious hematopoietic necrosis virus
      (IHNV).
AB  - Sexually mature female Chinook salmon Oncorhynchus tshawytscha with no prior
      history of exposure to infectious hematopoietic necrosis virus (IHNV) were
      susceptible to experimental infection induced by additions of virus to the water.
      The resulting infections resembled those observed among naturally infected
      hatchery and wild populations of Chinook salmon. Virus was detected as early as 4
      d post-exposure (p.e.) and subsequently in all virus-exposed fish that died or
      that were examined at 14 d p.e. when the study was terminated. The greatest
      concentrations of virus, up to 10(8) plaque-forming units (pfu) ml(-1), were
      found in the ovarian fluid at 13 to 14 d p.e., but the virus was also found in
      high concentrations in the gill, kidney/spleen and plasma. In contrast, the virus
      was not recovered from unexposed control adult salmon that died or were sampled
      at the end of the study. Despite detecting concentrations of IHNV in excess of
      10(7) pfu g(-1) of tissue, no specific microscopic lesions were found in IHNV
      exposed compared to unexposed control salmon. The results of this initial study
      suggest that virus in the spawning environment, either from adult salmon or other
      sources, may contribute to its rapid spread among adult Chinook salmon, thereby
      considerably increasing the prevalence of IHNV infection in both wild and
      hatchery populations of adult Chinook salmon.

PMID- 15264718
TI  - Pathology of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic
      salmon Salmo salar.
AB  - This is the first description of heart and skeletal muscle inflammation (HSMI), a
      novel disease affecting farmed Atlantic salmon Salmo salar in Norway. HSMI was
      first diagnosed in 1999, and there has since been a yearly increase in the number
      of recorded outbreaks. Atlantic salmon are commonly affected 5 to 9 mo after
      transfer to sea, but outbreaks have been recorded as early as 14 d following
      seawater transfer. Affected fish are anorexic and display abnormal swimming
      behaviour. Autopsy findings typically include a pale heart, yellow liver,
      ascites, swollen spleen and petechiae in the perivisceral fat. While mortality is
      variable (up to 20%), morbidity may be very high in affected cages. Until more
      accurate tests are available, HSMI is diagnosed on the basis of histopathology.
      The major pathological changes occur in the myocardium and red skeletal muscle,
      where extensive inflammation and multifocal necrosis of myocytes are evident.
      HSMI is transmissible and, although most likely caused by a virus, the causal
      agent has not yet been isolated. This paper describes clinical signs and
      pathology of HSMI from 3 field outbreaks in Norway. Microscopic lesions are
      compared and discussed in relation to published descriptions of pancreas disease
      (PD) and cardiomyopathy syndrome (CMS). It is concluded that HSMI is
      histopathologically distinguishable from PD and CMS.

PMID- 15264719
TI  - Effects of fish age and parasite dose on the development of whirling disease in
      rainbow trout.
AB  - We determined the ages at which juvenile rainbow trout Oncorhynchus mykiss became
      resistant to the effects of whirling disease following exposure to a range of
      parasite doses. Heretofore, the development and severity of whirling disease in
      salmonids was known to be generally dependent on the age or size of fish when
      first exposed to the triactinomyxon spores of Myxobolus cerebralis; larger, older
      individuals tended to be less diseased. However, no systematic determination had
      been made of the exact age at which fish become resistant to the development of
      the disease. We exposed rainbow trout at 9 ages (1 to 17 wk post-hatch) to 4
      parasite dose levels (0, 100, 1000 and 10,000 triactinomyxons per fish). Disease
      severity was measured using mortality, clinical signs, microscopic pathology, and
      myxospore counts. Disease and mortality were substantially reduced when exposure
      to the parasite occurred for the first time at 9 wk post-hatch (756 degree-days
      at 12 degrees C) or older. High doses elicited more disease among the younger age
      groups, but the effect was dampened in groups exposed at about 9 to 11 wk post
      hatch and absent thereafter. Rainbow trout reared in M. cerebralis-free waters
      for 9 wk post-hatch or longer, whether in the wild or in a hatchery situation,
      should experience greater survival and less disease than fish first exposed to
      the parasite at younger ages.

PMID- 15264720
TI  - Identification of a serine protease gene expressed by Myxobolus cerebralis during
      development in rainbow trout Oncorhynchus mykiss.
AB  - Serine proteases have been recognized as key factors in parasite physiology and
      disease development. We have identified a serine protease gene from Myxobolus
      cerebralis, MyxSP-1, the myxozoan parasite causing whirling disease in salmonid
      fishes. The amino acid sequence, as deduced from the cDNA sequence, included a
      catalytic residue arrangement similar to that of the chymotrypsin family of
      serine proteases. A real-time TaqMan polymerase chain reaction (PCR) analysis
      revealed differences in the transcription levels for the chymotrypsin-like
      protease as found in early, intermediate, and late developmental stages of the
      parasite in experimentally-infected rainbow trout Oncorhynchus mykiss. MyxSP-1
      transcription differed between individual tissues at each sampling point and in
      the same tissues over time (p < 0.0001). A nonradioactive mRNA in situ
      hybridization (ISH) protocol was developed to detect MyxSP-1 transcripts. Using a
      mixture of 3 digoxigenin-labeled antisense mRNA probes, MyxSP-1 transcription was
      observed in developmental stages of the parasite during the acute and chronic
      phases of the disease over a 240 d time period in infected rainbow trout tissues.
      MyxSP-1 transcription observed by ISH in cartilage and as associated with
      cartilage destruction was consistent with our real-time TaqMan PCR findings that
      demonstrated high levels of MyxSP-1 transcription during lesion development.
      Identifying genes encoding these enzymes and characterization of their functions
      can lead to the development of new chemotherapeutic protocols and vaccine
      approaches to control parasitic diseases.

PMID- 15264721
TI  - Effect of temperature on defense parameters in manila clam Ruditapes
      philippinarum challenged with Vibrio tapetis.
AB  - Brown Ring Disease (BRD), a vibriosis affecting the clam Ruditapes philippinarum,
      is present on the Atlantic coasts of Western Europe and is considered to be a
      cold water disease. The present work investigated the effect of temperature on
      immune response and its relationships with BRD development. Clams maintained at
      different temperatures (8, 14 and 21 degrees C) were experimentally challenged
      with the pathogen Vibrio tapetis, the etiologic agent of BRD. Results
      demonstrated significant effects of temperature on disease development and on
      hemolymph immune parameters including total and viable hemocyte counts, lysozyme
      and leucine aminopeptidase activities. Thirty days after challenge, clams
      maintained at 21 degrees C displayed significantly higher values for all the
      measured immune parameters in comparison to specimens incubated at 14 degrees C.
      Improved performance of the immune system was associated with a low BRD
      prevalence. The recovery process, which occured mainly at 21 degrees C, was
      associated with high percentages of viable hemocytes and high activities of
      leucine amino-peptidase and lysozyme. This laboratory study clearly demonstrates
      that temperature strongly affects BRD development and clam immune response during
      infection. Favourable immune status at higher temperature may confer upon the
      clam a better capacity to fight the disease agent, and therefore to recover more
      easily.

PMID- 15264722
TI  - In vitro effect of a buffered chelating agent and neomycin or oxytetracycline on
      bacteria associated with diseases of fish.
AB  - The antimicrobial agents used to treat bacterial fish diseases are archaic, and
      their uses may result in the emergence of drug-resistant bacterial strains. This
      study evaluated the in vitro antimicrobial activity of combinations of Tricide
      and neomycin or oxytetracycline on common disease-causing bacteria of fish and
      its possible use as an alternative treatment of these diseases. Tricide solutions
      containing of 8 mM United States Pharmacopeia (USP) disodium
      ethylenediaminetetraacetate dehydrate (chelator) and 20 mM USP 2-amino-2
      hydroxymethyl-1,3-propanediol (buffer) potentate the antimicrobial action of
      neomycin and oxytetracycline when reacted in vitro with Aeromonas hydrophila,
      Streptococcus iniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Serial
      passage of the test organisms in Tricide or Tricide and neomycin or
      oxytetracycline did not result in the development of resistant forms.
      Combinations of Tricide and neomycin or oxytetracycline reduced the amount of
      antibiotics necessary for fish therapy, render drug-resistant bacteria sensitive
      to antimicrobial therapy, may be used to decontaminate recently shipped fish, and
      should reduce the formation of antibiotic-resistant forms.

PMID- 15264723
TI  - Local anaesthetics--procaine (Novocaine, Ethocaine).

PMID- 15264724
TI  - Implementing intensive insulin therapy: development and audit of the Bath insulin
      protocol.
AB  - Intensive insulin therapy to control blood glucose has been found to reduce
      mortality among critically ill patients in a surgical intensive care unit, though
      a simple prescriptive insulin infusion protocol to achieve this has not been
      published previously. This study documents the development and routine use of a
      simple prescriptive intravenous insulin infusion protocol for critically ill
      patients and compares the results with previous practice. During development the
      protocol was optimized and practical issues of implementation addressed. The
      optimized protocol was then used for all ICU admissions, and a prospectively
      defined retrospective chart audit performed for the first month of use. Results
      were compared with a similar time period the previous year. In September 2002, 27
      admissions were started on the protocol. Blood glucose for the time on the
      protocol had a median value of 6.2 (IQR 5.9-7.1) mmol/l compared with 9.2 (IQR
      8.1-10.2) mmol/l for those on insulin in 2001. Blood glucose for the whole ICU
      stay for those on the protocol in 2002 had a median value of 6.6 (IQR 6.0-7.4)
      mmol/l compared with 8.6 (IQR 8.0-9.4) mmol/l in 2001. Blood glucose for all ICU
      patients in 2002 had a median value of 6.5 (IQR 6.0-7.3) mmol/l compared with 7.2
      (IQR 6.3-8.3) mmol/l in 2001. Three blood glucose recordings were less than 2.2
      mmol/l in September 2002. This study provides initial effectiveness and safety
      data for the Bath Insulin Protocol Further audits in a larger patient population
      are now needed.

PMID- 15264725
TI  - Modelling thirty-day mortality in the Acute Respiratory Distress Syndrome (ARDS)
      in an adult ICU.
AB  - Variables predicting thirty-day outcome from Acute Respiratory Distress Syndrome
      (ARDS) were analysed using Cox regression structured for time-varying covariates.
      Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral
      chest X-ray opacities, PaO2/FiO2 ratio of <200 and an acute precipitating event)
      were identified using a prospective computerized data base in a university
      teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of
      mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred
      in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8);
      ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day
      mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO2/FiO2 ratio was 92 (31),
      81% had four-quadrant chest X-ray opacification and lung injury score was 2.75
      (0.45). Average mechanical ventilator tidal volume was 10.3 ml/predicted kg
      weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II
      score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus
      indirect injury, 2.89 (1.45-5.76); PaO2/FiO2 ratio, 0.98 (0.97-0.99); operative
      versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were
      evident for PaO2/FiO2 ratio, operative versus non-operative category and
      ventilator tidal volume assessed as a categorical predictor with a cut-point of 8
      ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg
      predicted weight). Thirty-day survival was improved for patients ventilated with
      lower tidal volumes. Survival predictors in ARDS were multifactorial and related
      to patient-injury-time interaction and level of mechanical ventilator tidal
      volume.

PMID- 15264726
TI  - Perioperative intravenous ketamine infusion for the prevention of persistent post
      amputation pain: a randomized, controlled trial.
AB  - We hypothesized that perioperative ketamine administration would modify acute
      central sensitization following amputation and hence reduce the incidence and
      severity of persistent post-amputation pain (both phantom limb and stump pain).
      In a randomized, controlled trial, 45 patients undergoing above- or below-knee
      amputation received ketamine 0.5 mg x kg(-1) or placebo as a pre-induction bolus
      followed by an intravenous infusion of ketamine 0.5 mg x kg(-1) x h(-1) or normal
      saline for 72 hours postoperatively. Both groups received standardized general
      anaesthesia followed by patient-controlled intravenous morphine. The surface area
      of allodynia over the stump was mapped at days 3 and 6. Postamputation pain was
      assessed at days 3 and 6 and at 6 months postoperatively. We found no significant
      difference between groups in the surface area of stump allodynia or in morphine
      consumption. There was an unexplained, but significant, increase in the incidence
      of stump pain in the ketamine group at day 3. At six-month review, the incidence
      of phantom pain was 47% in the ketamine group and 71% in the control group. This
      did not reach statistical significance (P=0.28) as the power of the study was
      based on the search for a large treatment effect. The incidence of stump pain at
      six months was 47% in the ketamine group and 35% in the control group (P=0.72).
      There were no significant between-group differences in pain severity throughout
      the study period. Ketamine at the dose administered did not significantly reduce
      acute central sensitization or the incidence and severity of post-amputation
      pain.

PMID- 15264727
TI  - Post-suction recruitment manoeuvre restores lung function in healthy,
      anaesthetized pigs.
AB  - Endotracheal suction can cause partial lung collapse and hypoxia and alter lung
      mechanics. We investigated the effects of adding a recruitment manoeuvre directly
      after endotracheal suction to restore lung volume in volume-controlled
      ventilation and pressure-controlled ventilation modes. Five anaesthetized pigs
      were investigated. The effects of endotracheal suction with or without a
      recruitment manoeuvre were compared in random order. In volume-controlled
      ventilation, compliance decreased after suction from 33 +/- 5 to 26 +/- 6 ml x
      cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 6 ml x
      cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 8 +/- 4%
      (P<0.05), but had recovered at 30 minutes. In pressure-controlled ventilation,
      compliance decreased after suction from 34 +/- 3 to 25 +/- 7 ml x cmH2O(-1)
      (P<0.05), and 30 minutes later it remained decreased at 25 +/- 7 ml x cmH2O(-1).
      Venous admixture increased after suction from 5 +/- 2 to 13 +/- 7% (P<0.05), and
      had not recovered after 30 minutes, 10 +/- 4%. When a recruitment manoeuvre was
      applied directly after suction, no negative side-effects were registered in
      volume-controlled ventilation or pressure-controlled ventilation. We conclude
      that the impairment of lung mechanics and gas exchange induced by endotracheal
      suction can be prevented by a simple post-suction recruitment manoeuvre. Further
      studies are needed to identify a suitable suction recruitment manoeuvre in
      patients with diseased lungs.

PMID- 15264728
TI  - Is the degree of sensitivity to nondepolarizing muscle relaxants related to
      requirements for postoperative ventilation in patients with myasthenia gravis?
AB  - The purpose of this study was to examine whether the degree of sensitivity to
      nondepolarizing muscle relaxants is related to the requirement for postoperative
      ventilatory support in patients with myasthenia gravis. Thirty-six patients with
      myasthenia gravis undergoing trans-sternal thymectomy were monitored by
      electromyography in order to assess the neuromuscular response to vecuronium.
      After calibration to 100% of baseline electromyographic response values using an
      EMG monitor, incremental doses of 5, 10 and 20 microg/kg of vecuronium were
      administrated to produce 95% neuromuscular blockade and to obtain a cumulative
      dose-response curve for each patient. A univariable logistic regression with odds
      ratio was used to examine the predictive variables of prolonged postoperative
      ventilation. Depending on their postoperative ventilatory needs, patients were
      divided into an early extubation group and a prolonged ventilatory group. There
      were no significant differences between the two groups in terms of vecuronium
      ED95 (prolonged ventilation group: 23.2 +/- 18 microg/kg; early extubation group:
      23.2 +/- 18 microg/kg P=0.129) and vecuronium requirement to maintain less than
      25% neuromuscular blockade (prolonged ventilation group: 24 +/- 1.7 mg/kg; early
      extubation group: 3.8 +/- 4.5 mg/kg P=0.249). There were, however, significant
      differences in the incidence of a history of previous respiratory crises and the
      presence of bulbar palsy between the early extubation and prolonged ventilation
      groups. History of previous respiratory crisis (odds ratio (OR), 3.5; 95%
      confidence interval (CI), 1.0-13; P=0.03) and presence of bulbar palsy (OR, 3.7;
      95%CI, 0.9-15; P=0.049) were associated with the need for prolonged postoperative
      ventilation. However, we failed to demonstrate that the degree of sensitivity to
      nondepolarizing muscle relaxants was related to an increased requirement for
      postoperative ventilation in patients with myasthenia gravis.

PMID- 15264729
TI  - Crystalloid preload versus rapid crystalloid administration after induction of
      spinal anaesthesia (coload) for elective caesarean section.
AB  - Current methods of crystalloid preload administration prior to spinal anaesthesia
      for elective caesarean section are relatively ineffective in preventing
      hypotension. This study examined the relevance of the timing of the fluid
      administered. Fifty women were randomly allocated to receive either 20 ml x kg(
      1) of crystalloid solution during 20 minutes prior to induction of spinal
      anaesthesia (preload), or an equivalent volume by rapid infusion immediately
      after induction (coload). Significantly more patients in the coload group did not
      require vasopressor therapy pre-delivery (P=0.047). The coload group required a
      lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses
      for the treatment of maternal hypotension pre-delivery. There was no between
      group difference in either the total cumulative dose, or in the total number of
      doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid
      crystalloid administration after, rather than over 20 minutes before the
      induction of spinal anaesthesia for elective caesarean section, may be
      advantageous in terms of managing maternal blood pressure prior to delivery.

PMID- 15264730
TI  - Intraoperative patient warming using radiant warming or forced-air warming during
      long operations.
AB  - Forced-air warming is the most commonly used and effective method of active
      warming. A new radiant warming device (Suntouch, Fisher and Paykel) may provide
      an alternative when the skin surface available for warming is limited. We
      conducted a randomized controlled trial to compare the efficacy of the Suntouch
      radiant warmer and forced-air warming. With ethics committee approval 60 surgical
      patients having procedures anticipated to be more than two hours in duration were
      recruited. Patients were randomized to either radiant warming or forced-air
      warming. All intravenous fluids were warmed but prewarming was not used. The
      final intraoperative core temperatures (degrees C) for the radiant warming and
      forced-air warming groups were 36.0 +/- 0.5 and 36.4 +/- 0.6 (P=0.002)
      respectively. No other patient variables were significantly different. The
      Suntouch is not as effective as the forced air warming for intraoperative warming
      during long surgical procedures. The device may be useful when forced-air warming
      is not possible.

PMID- 15264732
TI  - Impediments to the use of ankle block in Australia.
AB  - Anaesthetic trainees and consultants who enrolled in a regional anaesthetic
      workshop completed a questionnaire regarding their own ankle block practice. The
      questionnaire focused on frequency of use, barriers to use, technique and
      perceived success rate. One hundred and twelve respondents participated, with 73%
      performing less than 10 ankle blocks per year. Forty-eight per cent believed that
      they did not have an appropriate operating list or a suitable patient, whilst 27%
      believed time constraints were the major barrier. Of those performing less than
      10 ankle blocks peryear, 22% cited lack of anatomical knowledge or technique as
      their major barrier and 71% perceived their success rate as medium to low. Eighty
      per cent performed their ankle block with the patient fully awake or sedated.
      Sixty-five per cent did not know the length of action of their ankle block. This
      survey supports recent suggestions that the practice of ankle block is under
      utilized. Teaching workshops and clinical training for peripheral nerve blocks
      should receive high priority for the future.

PMID- 15264731
TI  - Pethidine and skin warming to prevent shivering during endovascular cooling.
AB  - We tested the efficacy of pethidine and cutaneous warming to prevent shivering
      during percutaneous cooling in unanaesthetized patients. Ten patients scheduled
      for cranial neurosurgery received pethidine infusion and skin warming. The
      Setpoint internal heat-exchanging catheter was inserted and cooling to 33.5
      degrees C was started. Clonidine and chlorpromazine were given as "rescue
      medication" to treat shivering. General anaesthesia was planned to be induced
      after cooling was complete. Rewarming was initiated at dural closure. Three
      patients successfully completed the protocol, cooling to 33.8 degrees C at a
      median rate of 3.6 (range: 3.4-3.8) degrees C/h. Two patients cooled to 33.8
      degrees C but required treatment for shivering (cooling rate: 2.9 [2.8-3.1]
      degrees C/h). Four patients failed to cool adequately because of refractory
      shivering (cooling rate: 20 [1.5-2.9] degrees C/h). One patient did not shiver
      and yet failed to cool adequately (cooling rate: 0.76 degrees C/h). Rewarming was
      at a rate of 26 (1.2-4.3) degrees C/h. There were no significant complications
      arising from catheter placement. The combination of skin warming and pethidine
      was not reliable enough to be recommended for use during endovascular cooling in
      unanaesthetized patients.

PMID- 15264733
TI  - Efficacy of low-dose dexamethasone for preventing postoperative nausea and
      vomiting following strabismus repair in children.
AB  - We studied the efficacy of a range of doses of dexamethasone for prevention of
      postoperative nausea and vomiting following strabismus repair in children in a
      hospital-based, prospective, double-blinded, randomized, placebo-controlled
      trial. Two hundred and ten children were randomized to receive either
      dexamethasone in one of four dosages: 50 microg/kg (Group 1), 100 microg/kg
      (Group 2), 200 microg/kg (Group 3) and 250 microg/kg (Group 4) or normal saline
      (Group 5) prior to corrective surgery for strabismus. Anaesthesia was
      standardized and included nitrous oxide, pethidine, intubation and the use of
      muscle relaxant and reversal with neostigmine. Postoperative nausea and vomiting
      were evaluated in epochs of 0-2 hours, 2-6 hours and 6-24 hours after surgery.
      Parent satisfaction was assessed 24 hours after surgery and the operated eye was
      examined for wound infection and delayed healing one week later Dexamethasone was
      effective in preventing nausea and vomiting after strabismus repair: 57.1%
      children in Group 1, 42.9% in Group 2, 52.4% in Group 3, and 59.5% in Group 4
      were free from postoperative nausea and vomiting compared with 7.1% in placebo
      group. The lowest dose of 50 microg/kg was as efficacious as the higher dosages
      of dexamethasone during the 24 hours studied. Of the children who developed
      postoperative nausea and vomiting those who received dexamethasone had
      significantly fewer episodes than those in the placebo group. We conclude that
      dexamethasone 50 microg/kg is effective for the prevention of postoperative
      nausea and vomiting following strabismus repair in children.

PMID- 15264734
TI  - The differential flow of epidural local anaesthetic via needle or catheter: a
      prospective randomized double-blind study.
AB  - The extent of epidural anaesthesia and pattern of spread of contrast medium,
      using different injection techniques, has not been well documented. Therefore, in
      this prospective, randomized double-blind study, the extent of anaesthesia and
      pattern of spread of contrast medium following an epidural bolus injection, via
      either a Tuohy needle or an epidural catheter, were compared. The study had two
      parts. In the first, 59 of 79 patients scheduled for a lower extremity operation
      under epidural anaesthesia were randomly allocated to one of the two groups.
      Anaesthesia was achieved with an epidural injection of 10 to 15 ml (including a 3
      ml test dose) of 0.75% ropivacaine and fentanyl 25 microg via either a Tuohy
      needle (Group N, n=31) or a catheter (Group C, n=28). The level of sensory
      anaesthesia was recorded. In the second part, the remaining 20 patients were
      randomized to initially receive 5 ml of contrast medium via either a Tuohy needle
      (Group NE, n= 10) or a catheter (Group CE, n = 10). The extent of spread was
      recorded radiologically. Unilateral or missed blocks and additional dose
      requirement were absent in Groups N and C. No differences were found in the
      extent of sensory anaesthesia or the spread of contrast medium. Twenty per cent
      of catheter tips lay outside the lateral margins of the vertebral bodies. We
      found that an epidural bolus injection, via either a Tuohy needle or a catheter,
      made no difference in regard to spread of local anaesthetic or contrast medium in
      the epidural space.

PMID- 15264735
TI  - Comparison of laryngeal mask airway with tracheal tube for ophthalmic surgery in
      paediatric patients.
AB  - This study of sixty ASA grade 1 or 2 children, aged 1 to 12 years, undergoing
      elective ophthalmic procedures, compared the use of the laryngeal mask airway
      (LMA) with that of an endotracheal tube. Changes in intraocular pressure and
      haemodynamic parameters, and intraoperative and postoperative complications were
      measured Patients were randomly allocated into two groups of 30 patients. In
      group 1, the airway was secured with an LMA and in group 2 with an endotracheal
      tube. A standard technique of general anaesthesia incorporating positive pressure
      ventilation was used in both groups. The changes in intraocular pressure, heart
      rate (HR) and mean arterial pressure (MAP) were observed before and after
      insertion of the airway device, two minutes after insertion, and pre and post
      removal of the device. The incidence of airway complications was also noted.
      There was no significant change in mean intraocular pressure after insertion of
      the LMA, but removal caused a significant increase to 19.3 +/- 7.6 mmHg (from a
      baseline of 13.9 +/- 4.3 mmHg). In the endotracheal tube group, intubation
      increased the mean intraocular pressure significantly to 19.9 +/- 7.3 mmHg (from
      a baseline of 13.1 +/- 4.0 mmHg) and extubation caused an increase to 24.6 +/-
      10.4 mmHg which was clinically as well as statistically significant. The
      incidence of postoperative coughing was lower in the LMA group, but the incidence
      of vomiting higher. Two patients had displacement of the LMA during the
      procedure. We conclude that the use of an LMA is associated with less increase in
      intraocular pressure than the use of an endotracheal tube in children.

PMID- 15264736
TI  - Residual protein contamination of ProSeal laryngeal mask airways after two
      washing protocols.
AB  - The risk of prion protein cross-infection has focussed attention on the potential
      hazards of protein contamination of re-usable medical devices. This study
      determined the frequency of protein contamination of ProSeal laryngeal mask
      airways (PLMA) after two cleaning procedures and tested the hypothesis that the
      combination of hand- and machine-washing removes protein contamination more
      effectively than hand-washing alone. After clinical use fifty-four PLMAs were
      randomly allocated to be washed by hand or by hand then machine. All PLMAs were
      then autoclaved at 134 degrees C for 4 minutes. After processing, each PLMA was
      immersed in a 1.2% solution of erythrosin B and examined for uptake of stain. The
      site (outer surface, bowl and edges of the cuff airway and drain tube, finger
      strap) and severity (nil/mild/moderate/severe) of staining was scored by a
      blinded observer. There were no differences in the site or severity of staining
      between the two cleaning procedures. Staining was detected on 89% of PLMAs that
      were hand-washed and 78% of PLMAs that were hand-, then machine-washed (P=0.27).
      When staining occurred, it was mild in 98%, moderate in 2% and was never severe.
      Staining was more frequent on the edge than at any other location (all
      comparisons: P < or = 0.01). The strap never had any staining. We conclude that
      residual contamination of PLMAs with protein deposits is common even when machine
      washing is used to augment hand-washing before autoclaving. The infection risk
      associated with these deposits remains to be determined.

PMID- 15264737
TI  - How severe acute respiratory syndrome (SARS) affected the department of
      anaesthesia at Singapore General Hospital.
AB  - The effects of the outbreak of severe acute respiratory syndrome (SARS) on the
      Singapore General Hospital's Department of Anaesthesia are described. Urgent
      measures to protect staff and patients were implemented. Clear direction in
      administration issues and clinical pathways with good logistic support were
      essential. Anaesthetists were at risk and anaesthetic practice had to change in
      view of strict infection control provisions. Contingency planning for future
      infectious diseases outbreaks is required. Lessons can be learnt by hospitals yet
      to be visited by this virulent infection.

PMID- 15264738
TI  - Small simulators for teaching procedural skills in a difficult airway algorithm.
AB  - Difficulty with intubation, ventilation or both is a significant issue for
      anaesthetists. The American Society of Anesthesiologists' Guidelines for the
      Management of the Difficult Airway is an algorithm widely used when airway
      difficulties are encountered. Ideally, anaesthetic trainees should have access to
      simulators suitable for learning and practising how to manage airway
      difficulties, but most models have been designed primarily for resuscitation
      training. The aim of this study was to determine which small airway simulators
      could be used to practise steps in the Difficult Airway Algorithm (DAA). We
      identified the essential elements of the DAA relating to endotracheal intubation
      (laryngoscope, Trachlight and Fastrach), external laryngeal manipulation,
      dedicated airway devices (LMA, Combitube) and trans-tracheal ventilation using
      the Enk oxygen flow modulator (Cook). Each element was studied in adult airway
      models sold for airway management training. The DAA elements were studied in 16
      different airway models. No single model achieved our criteria of "good/very
      realistic" for all elements. All elements of the DAA could be used in the
      Difficult Airway Trainer Deluxe (MPL) and Bill (VBM/Mallinckrodt) but it would be
      necessary to acquire at least two trainers to achieve "good/very realistic" in
      all techniques studied. Anaesthetic departments planning to acquire small
      simulators for airway management training should undertake a training-needs
      analysis and apply this to the performance characteristics of the simulators.
      Generally, at least two airway training models will be needed to teach all steps
      of the DAA effectively.

PMID- 15264739
TI  - Recurrent atrial tachyarrhythmia triggered by percutaneous balloon rhizotomy of
      the trigeminal nerve.
AB  - Stimulation of sensory branches of the trigeminal nerve is known to cause sudden
      bradycardia (trigeminocardiac reflex). However we report a case where
      percutaneous balloon rhizotomy of the trigeminal ganglion provoked atrial
      tachyarrhythmias during two separate treatments. On both occasions the patient
      was treated with antiarrhythmic drugs and reverted to sinus rhythm within days.
      Our case demonstrates that surgery involving the trigeminal nerve may cause
      variable cardiovascular effects that are often clinically significant. Possible
      mechanisms and management of arrhythmias in this setting are discussed.

PMID- 15264741
TI  - Bilateral adductor vocal cord paresis following endotracheal intubation for
      general anaesthesia.
AB  - Recurrent laryngeal nerve palsy is a rare complication of endotracheal
      intubation. We report a case of bilateral vocal cord palsy following endotracheal
      intubation for general anaesthesia. The clinical picture was of hoarseness and
      aspiration suggestingpartialparesis, as complete bilateral recurrent laryngeal
      nerve palsy usually causes acute airway obstruction due to unopposed vocal cord
      adduction. Compression of the anterior branch of the recurrent laryngeal nerve
      between the cuff of the endotracheal tube and the posterior part of the thyroid
      cartilage was the likely mechanism. Ensuring that the cuff of the endotracheal
      tube is distal to the cricoid cartilage and that the pressure in the cuff is kept
      to the minimum required to prevent a gas leak should prevent this complication.

PMID- 15264740
TI  - Difficult extubation: calming the sympathetic storm.
AB  - Tracheal extubation can evoke an equally strong haemodyamic stress response as
      tracheal intubation. We present a patient with myocardial infarction who
      repeatedly failed tracheal extubation. He developed acute pulmonary oedema
      following each attempt at tracheal extubation due to sympathetic overactivity. A
      change of approach with extubation under propofol sedation followed by continued
      sympatholysis with dexmedetomidine infusion allowed successful extubation.

PMID- 15264743
TI  - Suspected case of venous air embolism in an infant undergoing hip arthrogram.
AB  - An otherwise well ten-week-old girl underwent an air contrast hip arthrogram and
      application of a hip spica for a developmentally dislocated hip. The child
      displayed signs consistent with venous air embolism after injection of 5 ml of
      air into the hip joint. These signs included a decrease in arterial haemoglobin
      oxygen saturation as measured by pulse oximetry, decreased end-tidal carbon
      dioxide level and tachycardia. The signs initially resolved, but the patient
      deteriorated with injection of a further 5 ml of air. The patient responded to
      cessation of injection and resuscitative measures. The infant remained well
      postoperatively. The need for the use of air to confirm intra-articular placement
      of the needle prior to injection of contrast during a hip arthrogram is
      questioned.

PMID- 15264742
TI  - Presumed central anticholinergic syndrome from inadvertent intravenous hyoscine
      hydrobromide (scopolamine) injection.
AB  - We present a case of presumed central anticholinergic syndrome due to a drug
      administration error. A 35-year-old woman was slow to emerge from anaesthesia for
      laparoscopic biliary surgery. Postoperative neurological and metabolic
      abnormalities were later diagnosed as central anticholinergic syndrome. Only
      after resolution of the clinical problems did the drug error origin of the
      syndrome become apparent. It was realized that hyoscine hydrobromide
      (scopolamine) had been inadvertently administered intraoperatively for biliary
      relaxation, instead of hyoscine butylbromide. This case report describes central
      anticholinergic syndrome and highlights potential problems involved for
      anaesthetists administering drugs they do not commonly use.

PMID- 15264744
TI  - Syringe production failure.

PMID- 15264745
TI  - Failed extubation of a double-lumen tube requiring a cricoid split.

PMID- 15264746
TI  - Glycopyrrolate as an alternative to vasopressor infusion for hypotension after
      carotid endarterectomy.

PMID- 15264747
TI  - Prone ventilation and aeromedical transport.

PMID- 15264748
TI  - Prolonged per-laryngeal endotracheal intubation in children: 40 years on--reply.

PMID- 15264749
TI  - Breathing filters in anaesthesia and ICU: an overview.

PMID- 15264750
TI  - Pressure or flow?

PMID- 15264751
TI  - Mechanical failure of a laryngoscope handle.

PMID- 15264752
TI  - [Simultaneous pancreas-kidney transplantation--an alternative option for the
      treatment of type 1 diabetes mellitus with renal failure].
AB  - INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is the only
      routinely used therapeutic option which can provide insulin independence,
      euglycemia and good renal replacement. AIMS: Analysis of the five years'
      experience of the first Hungarian SPK transplants. MATERIAL: From 29 October
      1998. through 31 December 2003. 32 SPK transplants were performed from 53 type 1
      diabetes mellitus patients with ESRD on the waiting list. Enteric drainage was
      performed in all transplanted patients in 20 combined with systemic venous
      drainage, whereas in 12 patients portal venous drainage was used. In 18 patients
      only maintenance immunosuppression was administered without ATG induction
      therapy. Anti IL-2R antibody, daclizumab was given as induction therapy in 14
      patients. RESULTS: 24 patients out of 32 transplanted are insulin independent
      with excellent renal function. 2 patients were lost in the perioperative period
      due to septic complication. 2 patients died 5 months after transplantation. 1
      patient became insulin dependent in 7 month following the SPK transplant, while
      preserving a marginal renal function. One patient became insulin dependent 2
      years after the SPK transplant and was returned to chronic hemodialysis treatment
      one more year later. 2 patients are insulin independent but lost his renal graft
      due to therapy resistant rejection. CONCLUSION: SPK transplant is a routinely
      used therapeutic option with good survival rate and good quality of life for type
      I diabetes mellitus patients with ESRD.

PMID- 15264753
TI  - [Continuous glucose monitoring system, as a valuable tool in the care of children
      and adolescents with diabetes mellitus].
AB  - INTRODUCTION: Good metabolic control of diabetic patients is mainly based on the
      results of self measured blood glucose levels. Important excursions of blood
      glucose may, however, be hidden in the usual case of 4-5 daily determinations.
      The aim of this paper was to give detailed information about this new diagnostic
      tool and to report the first Hungarian pediatric experiences with continuous
      glucose monitoring. METHOD: Continuous glucose monitoring system (Mini-Med) is
      able to monitor the changes of tissue glucose levels for up to 72 hours by
      measuring glucose concentration via a s.c. canula every 5 minutes. In its present
      form the results of continuous glucose monitoring cannot be observed real time by
      the patient, it provides useful information retrospectively mainly for the
      doctor. RESULTS: The sensor detected unexpectedly high fluctuation of glucose
      levels in several patients. It was possible to distinguish between nighttime
      hypoglycaemia (Somogyi-effect) or dawn phenomenon-induced morning hyperglycaemiae
      by the use of continuous glucose monitoring. Fever may influence peripheral
      circulation representing a limitation in the use (or evaluation) of continuous
      tissue glucose monitoring. The authors found good correlation between continuous
      glucose monitoring and self blood glucose monitoring results. The best
      correlation was observed in the low blood glucose range. CONCLUSIONS: The
      continuous glucose monitoring results provide useful information for the
      diabetologist in order to modify insulin treatment. Continuous glucose monitoring
      based changes in insulin treatment are reported to result in better long term
      metabolic control. Continuous glucose monitoring in the near future will
      obviously play a primary role in insulin pump therapy where it will provide
      glucose result for the pump.

PMID- 15264754
TI  - [Icterus of the newborn caused by indirect bilirubin--recent progress].
AB  - Recently a big shift has taken place in the judgment and treatment of jaundice in
      newborn, caused by increased unconjugated bilirubin level. New techniques evolved
      for assessing the prognosis of developing jaundice. An important major discovery
      is the antioxidant effect of bilirubin. We have a broader range of knowledge
      concerning the mechanism of bilirubin toxicity and for judging the chance of
      developing kernicterus. The prevention techniques do not stop at prohibiting anti
      D immunisation but go on to preventing hydrops foetalis, the life-threatening
      form of haemolytic disease. There are data about the complications of
      phototherapy and EPO treatment for prolonged anaemia.

PMID- 15264755
TI  - [Beliefs, hopes, misbeliefs (connection between the pharmaceutical industry and
      clinical research)].

PMID- 15264756
TI  - [Position statement of the Hungarian Medical and Health Education Society
      regarding medical school admissions in connection with the two-step high school
      graduation examination].

PMID- 15264757
TI  - [Procedure for the qualification of scientific conferences and congresses].

PMID- 15264758
TI  - [Treatment of schizophrenia].

PMID- 15264759
TI  - [Treatment of recidiv cornea erosion].

PMID- 15264760
TI  - [Philip Hauser M.D. (1832-1925)].

PMID- 15264761
TI  - [Plavix--medicine of the year 2003].

PMID- 15264762
TI  - Rodent vendor apparent source of mouse parvovirus in sentinel mice.
AB  - Mouse parvovirus (MPV) has been increasingly prevalent in laboratory animal
      facilities, and the source of infection often can be difficult to determine.
      After 4 years of sporadic MPV detected in our sentinel mice and continual failure
      to identify index cases in colony mice, we developed a regimen to house newly
      arrived vendor mice in large sterile cages with a high stocking density. Some of
      these mice were retained in isolation after the remaining mice were deployed as
      sentinels. After detecting MPV seropositive sentinel mice 4 weeks after
      introduction to the mouse colonies in one facility, the remaining naive mice that
      had been previously housed with those sentinels also tested positive for MPV,
      despite never having been exposed to colony mice. These results suggest that
      commercially bred mice intended for use as sentinels may, in fact, arrive at
      animal facilities already infected with MPV. Depending upon numerous factors,
      including the health surveillance methods used, it is possible that a low
      prevalence of MPV may exist undetected at rodent vendors.

PMID- 15264763
TI  - Evaluation of cage micro-environment of mice housed on various types of bedding
      materials.
AB  - A variety of environmental factors can affect the outcomes of studies using
      laboratory rodents. One such factor is bedding. Several new bedding materials and
      processing methods have been introduced to the market in recent years, but there
      are few reports of their performance. In the studies reported here, we have
      assessed the cage micro-environment (in-cage ammonia levels, temperature, and
      humidity) of mice housed on various kinds of bedding and their combinations. We
      also compared results for bedding supplied as Nestpaks versus loose bedding. We
      studied C57BL/6J mice (commonly used) and NOD/LtJ mice (heavy soilers) that were
      maintained, except in one study, in static duplex cages. In general, we observed
      little effect of bedding type on in-cage temperature or humidity; however, there
      was considerable variation in ammonia concentrations. The lowest ammonia
      concentrations occurred in cages housing mice on hardwood bedding or a mixture of
      corncob and alpha cellulose. In one experiment comparing the micro-environments
      of NOD/LtJ male mice housed on woodpulp fiber bedding in static versus ventilated
      caging, we showed a statistically significant decrease in ammonia concentrations
      in ventilated cages. Therefore, our data show that bedding type affects the micro
      environment in static cages and that effects may differ for ventilated cages,
      which are being used in vivaria with increasing frequency.

PMID- 15264764
TI  - To enrich or not to enrich: providing shelter does not complicate handling of
      laboratory mice.
AB  - Environmental enrichment (EE) is used in laboratory animal housing to provide
      stimuli exceeding those of barren cages and is intended to improve the welfare of
      captive animals. It is argued that when laboratory mice can routinely retreat in
      sheltering objects when humans are present, they do not habituate to humans and
      continue to shy away, thereby increasing the time needed for husbandry and
      testing procedures. To this date very limited research has been carried out to
      determine whether providing EE in the form of shelter interferes with the
      habituation of mice to humans and thus complicates catching and handling them. We
      housed 20 FVB (inbred) and 20 NMRI (outbred) male mice in standard cages and
      another 20 FVB and 20 NMRI male mice in cages enriched with two PVC conduits.
      When the mice were 10 weeks old, measurements of food and water consumption,
      weight, latency of catching, and a behavior score in response to handling during
      a sham subcutaneous injection were performed weekly for 4 consecutive weeks. Food
      and water consumption and weight were influenced by strain, but the presence of
      EE in the home cage did not affect these parameters as much. Outbred mice ate,
      drank, and weighed more than did the inbred animals, but they did not
      significantly gain weight during the course of the 4 testing weeks. Cage
      enrichment in the form of PVC conduits decreased the time needed to catch outbred
      animals and did not increase the time needed to catch mice from the inbred
      strain. Furthermore, no differences in resistance to being held during the sham
      injection could be detected between animals from the enriched versus non-enriched
      group. These results indicate that EE in the form of sheltering objects does not
      complicate catching or handling mice and that allowing access to enrichment in
      the laboratory cage, which has been shown to have positive effects on welfare,
      does not interfere with the management or cost of laboratory animals.

PMID- 15264765
TI  - Endotracheal tubes versus laryngeal mask airways in rabbit inhalation anesthesia:
      ease of use and waste gas emissions.
AB  - In this study, we compared two endotracheal tubes (cuffed [Murphy Eye type] and
      uncuffed [Cole type]) and a pediatric laryngeal mask airway (LMA) with respect to
      their ease of use in rabbits and their capacities to limit waste isoflurane
      emissions. Animals (New Zealand White, 3.3 to 5.0 kg, n = 8) were sedated with
      intramuscular ketamine (50 mg/kg) and xylazine (10 mg/kg). After 5 min, the
      larynx was numbed with cetocaine, an intubation device was positioned, and
      anesthesia was maintained with isoflurane (2%) in oxygen (1 liter/min). Real-time
      atmospheric isoflurane emissions were assessed at the rabbit's oral commissure
      and in the operator's breathing zone (45 cm from the rabbit's nose) by using a
      portable infrared spectrophotometer. The LMA was placed more easily than was
      either endotracheal tube, especially by novices. The cuffed tube was positioned
      more readily than was the uncuffed variant. All three devices emitted isoflurane.
      The concentrations measured at the oral commissure for the LMA (mean +/- standard
      error, 8.4 +/- 0.6 ppm) were modestly higher than those acquired for the cuffed
      (6.7 +/- 0.5 ppm) and uncuffed (6.3 +/- 0.4 ppm) endotracheal tubes; the
      difference between the LMA and uncuffed tube was significant (P = 0.012).
      Isoflurane was not detected in the operator's breathing zone. These data show
      that the uncuffed endotracheal tube (usually used to anesthetize birds and
      reptiles) and the pediatric LMA can be used in rabbits as readily as a cuffed
      tube. In addition, our findings indicate that tradeoffs will be required in
      selecting a delivery system for this species, as the easiest apparatus (the LMA)
      also emits the most isoflurane waste.

PMID- 15264766
TI  - Vitamin A toxicity and vitamin E deficiency in a rabbit colony.
AB  - Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit
      breeding colony and was associated with reproductive abnormalities, abortions,
      and poor survivability of kits in the breeding colony. Paresis and muscular
      dystrophy were noted in juvenile rabbits. Another group of New Zealand White
      rabbits from the same commercial colony was used to assess the effect of vitamin
      E-based therapy on clinical signs, reproduction, and vitamin A and E serum and
      liver levels. Blood samples were taken before and after dietary changes and
      vitamin E therapy. Serum vitamin E remained low after feeding a diet containing
      the recommended levels of vitamin E. Administration of vitamin E for 2 weeks
      lowered the serum vitamin A levels and increased the vitamin E serum and liver
      levels. In conclusion, vitamin E therapy appears to be an effective treatment for
      hypervitaminosis A.

PMID- 15264767
TI  - Vaginal and cervical atresia in a cynomolgus macaque.
AB  - A female cynomolgus monkey presented clinically with a caudal abdominal mass
      noted on a prestudy physical examination. No other clinical abnormalities were
      noted. An ultrasound examination revealed a mass approximately 2 cm in diameter,
      which contained fluid with a granular "free-floating" appearance. Within a month
      the mass enlarged and was visible from external examination. Exploratory
      laparotomy revealed a mass encompassing the uterus, both ovaries, bladder, and
      rectum. The animal was euthanized under anesthesia, and the mass was removed,
      examined, and submitted for histopathology. A diagnosis of vaginal and cervical
      atresia was made. To the author's knowledge, this is the first description of
      vaginal and cervical atresia in a laboratory nonhuman primate.

PMID- 15264768
TI  - Brine shrimp dispenser.

PMID- 15264769
TI  - Operant conditioning.

PMID- 15264770
TI  - Deep brain stimulation for hyperkinetic disorders.
AB  - Deep brain stimulation (DBS) has a record of safety and efficacy for an expanding
      range of indications. Recently,the Food and Drug Administration provided approval
      through a Humanitarian Device Exemption for DBS of the globus pallidus internus
      and subthalamic nucleus for the treatment of dystonia. There is increasing
      clinical experience demonstrating that DBS is also effective for other
      hyperkinetic disorders such as chorea from a variety of causes. The selection
      criteria, intraoperative targeting, and the postoperative management of DBS for
      hyperkinetic disorders are discussed.

PMID- 15264771
TI  - Deep brain stimulation in the treatment of dyskinesia and dystonia.
AB  - Deep brain stimulation (DBS) has become a mainstay of treatment for patients with
      movement disorders. This modality is directed at modulating pathological activity
      within basal ganglia output structures by stimulating some of their nuclei, such
      as the subthalamic nucleus (STN) and the globus pallidus internus (GPi), without
      making permanent lesions. With the accumulation of experience, indications for
      the use of DBS have become clearer and the effectiveness and limitations of this
      form of therapy in different clinical conditions have been better appreciated. In
      this review the authors discuss the efficacy of DBS in the treatment of dystonia
      and levodopa-induced dyskinesias. The use of DBS of the STN and GPi is very
      effective for the treatment of movement disorders induced by levodopa. The
      relative benefits of using the GPi as opposed to the STN as a target are still
      being investigated. Bilateral GPi stimulation is gaining importance in the
      therapeutic armamentarium for the treatment of dystonia. The DYT1 forms of
      generalized dystonia and cervical dystonias respond to DBS better than secondary
      dystonia does. Discrimination between the diverse forms of dystonia and a better
      understanding of the pathophysiological features of this condition will serve as
      a platform for improved outcomes.

PMID- 15264772
TI  - Comparison of pallidal and subthalamic deep brain stimulation for the treatment
      of levodopa-induced dyskinesias.
AB  - Deep brain stimulation (DBS) can relieve dyskinesias effectively and safely. This
      modality is applied most commonly in the treatment of dyskinesias associated with
      levodopa therapy for Parkinson disease. The subthalamic nucleus (STN) and globus
      pallidus internus (GPi) are the most common surgical targets. Deep brain
      stimulation of the GP has a direct antidyskinetic effect, whereas relief of
      dyskinesias by DBS of the STN depends on postoperative reduction of dopaminergic
      medications. Outcomes are similar for DBS in these two sites despite the
      different mechanisms by which the stimulation relieves dyskinesias. Deep brain
      stimulation of the STN has become the surgical treatment of choice in many
      movement disorders programs but this modality has not been compared with DBS of
      the GPi in randomized controlled trials, and the superiority of one site over the
      other remains unproven. In the absence of data demonstrating superiority,
      selection of the stimulation target should be individualized to meet the needs of
      each patient. Selection of the target should be based on the patient's most
      disabling symptoms, response to medications (including side effects), and the
      goals of therapy, with consideration given to the different antidyskinetic
      effects of DBS of the STN and GPi.

PMID- 15264773
TI  - Microelectrode-guided implantation of deep brain stimulators into the globus
      pallidus internus for dystonia: techniques, electrode locations, and outcomes.
AB  - Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a
      promising new procedure for the treatment of dystonia. The authors present their
      technical approach for placement of electrodes into the GPi in awake patients
      with dystonia, including the methodology used for electrophysiological mapping of
      the GPi in the dystonic state, clinical outcomes and complications, and the
      location of electrodes associated with optimal benefit. Methods. Twenty-three
      adult and pediatric patients who had various forms of dystonia were included in
      this study. Baseline neurological status and improvement in motor function
      resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating
      Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic
      resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording,
      and intraoperative test stimulation to determine thresholds for stimulation
      induced adverse effects. Electrode locations were measured on computationally
      reformatted postoperative MR images according to a prospective protocol.
      Conclusions. Physiologically guided implantation of DBS electrodes in patients
      with dystonia is technically feasible in the awake state in most cases, with low
      morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are
      similar to those of globus pallidus externus neurons, such that the two nuclei
      must be distinguished by neuronal discharge patterns rather than by rates. Active
      electrode locations associated with robust improvement (> 50% decrease in BFMDRS
      score) were located near the intercommissural plane, at a mean distance of 3.7 mm
      from the pallidocapsular border. Patients with juvenile-onset primary dystonia
      and those with the tardive form benefited greatly from this procedure, whereas
      benefits for most secondary dystonias and the adult-onset craniocervical form of
      this disorder were more modest.

PMID- 15264774
TI  - The Canadian multicenter trial of pallidal deep brain stimulation for cervical
      dystonia: preliminary results in three patients.
AB  - OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is
      beneficial for generalized dystonia and has been proposed as a treatment for
      cervical dystonia. The Canadian Stereotactic/Functional and Movement Disorders
      Groups designed a pilot project to investigate the following hypothesis: that
      bilateral DBS of the GPi will reduce the severity of cervical dystonia at 1 year
      of follow up, as scored in a blinded fashion by two neurologists using the
      Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcome
      measures included pain and disability subscores of the TWSTRS, Short Form-36
      quality of life index, and the Beck Depression Inventory. METHODS: Three patients
      have undergone surgery in Calgary with a follow-up duration of 7.4 +/- 5.9 months
      (mean +/- standard deviation). One patient underwent inadvertent ineffective
      stimulation for the first 3 months and did not experience a benefit until DBS
      programming was corrected. All three patients had rapid response to stimulation,
      with the muscles relaxing immediately and abnormal movements improving within
      days. Total TWSTRS scores improved by 79%, and severity subscores improved
      significantly, from 15.7 +/- 2.1 to 7.7 +/- 2.9 (paired t-test, p = 0.02). Pain
      and disability subscores improved from 25.5 +/- 4.1 to 3.3 +/- 3.1 (paired t
      test, p = 0.002) and from 13.3 +/- 4.9 to 3.3 +/- 4.2 (paired t-test, p = 0.06),
      respectively. CONCLUSIONS: Although it is too early to reach broad conclusions,
      this report of preliminary results confirms the efficacy of DBS of the GPi for
      cervical dystonia.

PMID- 15264775
TI  - Immediate and sustained relief of levodopa-induced dyskinesias after dorsal
      relocation of a deep brain stimulation lead. Case report.
AB  - The authors demonstrate that high-frequency electrical stimulation dorsal to the
      subthalamic nucleus (STN) can directly suppress levodopa-induced dyskinesias.
      This 63-year-old woman with idiopathic Parkinson disease underwent surgery for
      placement of bilateral subthalamic deep brain stimulation (DBS) electrodes to
      control progressive rigidity, motor fluctuations, and levodopa-induced
      dyskinesias. The model 3389 DBS leads were implanted with microelectrode
      guidance. Magnetic resonance imaging confirmed proper placement of the leads.
      Postoperatively the patient exhibited improvement in all of her parkinsonian
      symptoms; however, her right leg dyskinesias had not improved. Based on their
      previous experiences treating levodopa-induced dyskinesias with subthalamic
      stimulation through the more dorsally located contacts of the model 3387 lead,
      the authors withdrew the implanted 3389 lead 3 mm. Following relocation of the
      lead they were able to suppress the right leg dyskinesias by using the most
      dorsal contacts. The patient's dopaminergic medication intake increased slightly.
      These findings indicate that electrical stimulation dorsal to the STN can
      directly suppress levodopa-induced dyskinesias independent of dopaminergic
      medication changes. The 3389 lead may provide inadequate coverage of the
      subthalamic region for some patients.

PMID- 15264776
TI  - Treatment of hemiballismus with stereotactic pallidotomy. Case report and review
      of the literature.
AB  - Hemiballismus is a relatively rare movement disorder that is characterized by
      uncontrolled, random, large-amplitude movements of the limbs. It is usually
      caused by a vascular lesion that involves the contralateral subthalamic nucleus
      (STN) (also known as the nucleus hypothalamicus or corpus luysi) and its afferent
      and efferent pathways. The authors present a case of medically intractable
      hemiballismus in a 70-year-old woman who was successfully treated with
      stereotactic posteroventral pallidotomy. In agreement with the data reported
      earlier by other groups, the microrecording performed during the pallidotomy
      showed a decreased rate of firing of the pallidal neurons, supporting the theory
      of impaired excitatory input from the STN to the internal part of the globus
      pallidus. Stereotactic pallidotomy may be the procedure of choice in the
      treatment of medically intractable hemiballismus. Intraoperative microrecording
      significantly improves the precision of the stereotactic targeting and should be
      considered a standard part of the pallidotomy protocol.

PMID- 15264777
TI  - Reduction of leg pain and lower-extremity weakness for 1 year with Oxiplex/SP gel
      following laminectomy, laminotomy, and discectomy.
AB  - OBJECT: Although good surgical technique is effective in reducing postoperative
      epidural fibrosis, compression or tethering of the nerve root may cause recurrent
      radicular pain and physical impairment. The implantation of a bioresorbable gel
      on the dura may further decrease the amount of scar formation after surgery and
      thus improve the patient's ability to perform activities of daily living (ADL).
      This study is a 12-month evaluation of the safety and effectiveness of Oxiplex/SP
      Gel (FzioMed, Inc., San Luis Obispo, CA) in the reduction of pain and
      radiculopathy after lumbar discectomy. METHODS: A pilot randomized single-blind
      multicenter clinical trial was conducted to evaluate the performance of
      Oxiplex/SP Gel in patients who underwent surgery for unilateral herniation of the
      lumbar disc at L4-5 or L5-S1. Eighteen patients with severe leg pain and lower
      extremity weakness (11 women and seven men) were randomly assigned
      intraoperatively to receive the gel at the conclusion of surgery (treatment
      group) or to undergo surgery alone (control group). Self-assessment
      questionnaires (Lumbar Spine Outcomes Questionnaire) to assess pain, symptoms,
      and ADL were completed preoperatively and at scheduled postoperative intervals
      (30 days, 90 days, 6 months, and 12 months). The authors examined the spine and
      lower extremities of patients scheduled for discectomy to assess neurological
      function and pain. Treated patients received sufficient Oxiplex/SP Gel (1-3 ml)
      to coat the nerve root and fill the epidural space. Postoperative clinical
      evaluations were performed at 30 and 90 days. Patients completed the self
      assessment questionnaires at baseline and were contacted by telephone or mail for
      the completion of the postoperative self-assessment questionnaires. Surgical
      procedures were well tolerated; no device-related adverse events and no
      clinically significant laboratory results were reported. The 11 patients with
      severe leg pain and lower-extremity weakness who were treated with Oxiplex/SP Gel
      had a reduction in those symptoms at 30 days, 90 days, 6 months, and 12 months
      after discectomy, compared with the seven control patients who underwent surgery
      only. CONCLUSIONS: Oxiplex/SP Gel was easy to use and safe in patients who
      underwent unilateral discectomy. A greater benefit in clinical outcome measures
      was seen over the 12-month follow-up period in gel-treated patients.

PMID- 15264778
TI  - Intradural ventral and ventrolateral tumors of the spinal cord: surgical
      treatment and results.
AB  - OBJECT: To improve results of surgical treatment of ventral and ventrolateral
      tumors of the spinal cord, the authors analyzed surgical approaches, defined the
      indications for various approaches, and assessed the clinical results. METHODS:
      Between 1993 and 2004 the authors treated 360 patients: 43 of them had dorsal,
      177 dorsolateral, 33 ventral, and 107 had ventrolateral intradural extramedullary
      tumors. Among 140 patients with intradural extramedullary ventral and
      ventrolateral tumors, neuromas were seen in 56 and meningiomas in 84. Of the 140
      patients studied, tumors were removed totally in 102 (74%), subtotally in 30
      (21%), and partially in eight (5%). After ventrolateral and dorsolateral
      approaches were introduced in 1996, tumors in ventral or ventrolateral locations
      have been removed totally or subtotally. In the group of patients with
      meningiomas, 41 of the lesions were the meningothelial type, 22 were
      transitional, 12 fibroblastic, four psammomatous, three were angiomatous, one was
      atypical, and one was malignant. Tumors in the neuroma group were schwannomas in
      45 patients and neurofibromas in 11. Postoperatively, recovery was observed in 70
      patients (50%), improvement in 53 (38%), no change in 10 (7%), and deterioration
      in seven (5%). At follow-up evaluation recovery was noted in 76 patients,
      improvement in 58, no change in four, and in two patients the neurological
      symptoms were worse than before the operation. CONCLUSIONS: Surgical routes to
      extramedullary tumors should be chosen based on the location of the tumor, its
      spread, and the region in which it is localized.

PMID- 15264779
TI  - History of spinal surgery: one neurosurgeon's perspective.
AB  - Spinal surgery has advanced from decompression procedures to complex spinal
      reconstruction and internal stabilization within the last 25 years, as a result
      of a broad-based technological boom that began in the 1970s with the advent of
      spinal computerized tomography and magnetic resonance imaging. These
      technological advances have coincided with, and developed as a result of, the
      concomitant rise of a complex, economically driven consortium of innovative
      surgeons and researchers, academic institutions, government agencies, and private
      industry, to form a Medical-Industrial Complex (MeIC). A major growth industry
      has formed, resulting in an overall societal benefit. Nevertheless, it has
      impacted graduate medical education and has significantly increased the cost of
      treating spinal disorders. Back pain and spinal disorders are a major societal
      health problem that is associated with a high demand for treatment services.
      There is a potential for abuse as well as a benefit in offering these services.
      The MeIC has contributed to the overall rise in the cost of health care insurance
      and in the migration of manufacturing jobs abroad as a solution for lowering
      production costs. The increased cost has had a negative impact on local and
      regional economies.

PMID- 15264780
TI  - History of spine surgery in the ancient and medieval worlds.
AB  - There is a paucity of surviving texts from ancient and medieval times that can
      shed light on the early development of spine surgery. Nevertheless, the author
      reviews many of the available books and fragments and discusses early
      developments in the field of spine surgery from the point of view of physicians'
      personalities, general themes, and actual surgical practices. For purposes of an
      overview and to highlight changing trends in spine surgery, he divides the paper
      into four eras of medicine: 1) Egyptian and Babylonian; 2) Greek and early
      Byzantine; 3) Arabic; and 4) medieval.

PMID- 15264781
TI  - Medieval management of spinal injuries: parallels between Theodoric of Bologna
      and contemporary spine surgeons.
AB  - In recent decades there have been revolutionary technological advances in the
      management of traumatic spinal column injuries. Despite these advances, the basic
      principles of reduction and stabilization of vertebral fractures and dislocations
      remain similar to those proposed by ancient and medieval physicians. Theodoric of
      Bologna, in his text Chiurgica de Theodoric (ca. AD 1267), described an
      extracorporeal approach to the management of traumatic spinal column
      misalignments. Surprisingly, his techniques are still used in many instances by
      contemporary spine surgeons, despite the availability of a more advanced
      technological armamentarium than that existent in medieval times.

PMID- 15264782
TI  - Nelson's wound: treatment of spinal cord injury in 19th and early 20th century
      military conflicts.
AB  - During the first half of the 19th century, warfare did not provide a background
      for a systematic analysis of spinal cord injury (SCI). Medical officers
      participating in the Peninsular and Crimean Wars emphasized the dismal prognosis
      of this injury, although authors of sketchy civil reports persuaded a few
      surgeons to operate on closed fractures. The American Medical and Surgical
      History of the War of the Rebellion was the first text to provide summary of
      results in 642 cases of gunshot wounds of the spine. The low incidence of this
      injury (0.26%) and the high mortality rate (55%) discouraged the use of surgery
      in these cases. Improvements in diagnoses and the introduction of x-ray studies
      in the latter half of the century enabled Sir G. H. Makins, during the Boer War,
      to recommend delayed intervention to remove bone or bullet fragments in
      incomplete injuries. The civil experiences of Elsberg and Frazier in the early
      20th century promoted a meticulous approach to treatments, whereas efficient
      transport of injured soldiers during World War I increased the numbers of
      survivors. Open large wounds or cerebrospinal fluid leakage, signs of cord
      compression in recovering patients, delayed clinical deterioration, or
      intractable pain required surgical exploration. Wartime recommendations for
      urological and skin care prevented sepsis, and burgeoning pension systems
      provided specialized longterm rehabilitation. By the Armistice, the effective
      surgical treatment and postoperative care that had developed through decades of
      interaction between civil and military medicine helped reduce incidences of
      morbidity and dispel the hopelessness surrounding the combatant with an SCI.

PMID- 15264783
TI  - A brief history of therapy for traumatic spinal cord injury.
AB  - There are few more devastating injuries that afflict man than those associated
      with spinal cord injury (SCI). The economic, psychological, and social impact are
      encompassing and enormous to the individual and society. During the last several
      years, there has been a renewed interest in the study of SCI, with the hope of
      finding a cure. It is appropriate, then, to examine the efforts accomplished
      throughout medical history. With this retrospective view, potential avenues for
      future treatment become more apparent and clear. As in the past, the integration
      of basic science and clinical innovation will create the path toward progress for
      treatment of this disease.

PMID- 15264784
TI  - Sciatica: a historical perspective on early views of a distinct medical syndrome.
AB  - The authors offer a brief overview of early theories and treatments of sciatica.
      Tracing medical traditions through early Greek, Roman, and Eastern epochs, the
      authors demonstrate the slow sequential steps that were required to delineate
      this disease as a uniquely human affliction.

PMID- 15264785
TI  - The "tract" of history in the treatment of lumbar degenerative disc disease.
AB  - In this paper past, present, and future treatments of degenerative disc disease
      (DDD) of the lumbar spine are outlined in a straight forward manner. This is done
      to review previous knowledge of the disease, define current treatment procedures,
      and discuss future perspectives. An analysis of a subject of this magnitude
      dictates that one describes as accurate a history as possible: an
      anatomical/historical "tract" with emphasis on all possible deviations. Although
      spinal disorders have been recognized for a long time, the view of DDD as a
      particular disease entity is a more recent development. In this paper, the
      authors attempt to outline the history of DDD of the lumbar spine in an unbiased
      and scientific fashion. Physiological, diagnostic, and therapeutic implications
      will all be addressed in this study.

PMID- 15264786
TI  - Anterior cervical plates: a historical perspective.
AB  - The development of anterior cervical plates (ACPs) represents a rapidly changing
      aspect of spine surgery. This paper focuses on a historical overview of ACPs. The
      authors discuss the disadvantages of earlier generations of plates and
      demonstrate how current plates have been designed to overcome the presumed
      shortcomings of their predecessors. This historical review begins with the
      earliest plates--unrestricted backout plates--and moves on to newer plates-
      restricted backout plates and their different subcategories. Virtually all modern
      ACPs work equally well in cervical stabilization; however, there are differences
      in design that warrant future studies to understand the long-term performances of
      different plates.

PMID- 15264787
TI  - The evolution of posterior cervical and occipitocervical fusion and
      instrumentation.
AB  - The past several decades have been the setting for a remarkable evolution of
      spinal instrumentation technology. The advancements that have been made have
      allowed previously complex disorders of the cervical spine, the atlantoaxial
      articulation, and the occipitocervical junction to be managed more effectively
      with direct methods of internal fixation and arthrodesis. This has resulted in
      improvements in patient outcomes and fusion success rates. The improved strength
      of instrumentation constructs allows minimal, if any, external bracing, obviating
      the need for a halo orthosis in many cases. In this paper the authors review key
      events that have occurred in neuroimaging, biomechanical testing, and the
      development of fusion and instrumentation constructs.

PMID- 15264788
TI  - History of instrumentation for stabilization of the subaxial cervical spine.
AB  - In the past several decades methods have been developed to stabilize the subaxial
      cervical spine both posteriorly and anteriorly. Methods of posterior
      stabilization have progressed from interspinous wiring, through facet wiring and
      sublaminar wiring, to the lateral mass screws with plates and rods that are in
      use today. Plates for anterior stabilization have evolved from rigid plates
      requiring bicortical screws through those used with unicortical locking screws,
      to dynamic load-sharing plates used with variable angle screws. The original
      description of spinous process wiring was published by Hadra in 1891. In 1942
      Rogers described the interspinous wiring method used for trauma-induced cervical
      instability, which was modified by Bohlman in 1985 (triple wiring technique).
      Luque rods with sublaminar wires were introduced in the late 1970s to address
      multilevel and occipitocervical instability. Facet wiring was developed in 1977
      by Callahan to address the problem of stabilization when laminae are not present.
      Wiring remained the method used until Roy-Camille introduced the lateral mass
      screw-plate construct in the 1980s. The first plate for anterior stabilization
      was designed by Orozco and Llovet in 1970 and was later refined by Caspar; this
      was a rigid plate with bicortical screws. Morscher devised unicortical locking
      screws in the 1980s. The latest concept of dynamic load-sharing plates with
      variable angle screws was developed in 2000. In this article historical landmarks
      in surgical methods for the stabilization of the subaxial cervical spine are
      reviewed.

PMID- 15264789
TI  - History of posterior thoracic instrumentation.
AB  - The term "backbone" appears in many expressions used in modern day society. In
      any scenario, it has one central meaning: stability. Best defined as a foundation
      that is able to sustain multiple stressors without adversely affecting integrity,
      the commonly and appropriately termed backbone of humans is the spinal column. As
      the central focus of stability in our species, the spine is subject to a great
      degree of trauma and mechanical forces. A variety of methods have been developed
      throughout history in the treatment of spinal column injury. Initial treatment
      involved the use of simple traction devices for the reduction of spinal
      fractures; these have evolved to include the current insertion of spinal
      instrumentation. The authors review the historical treatment and development of
      posterior instrumentation for thoracic spinal injury.

PMID- 15264790
TI  - Evolution of the lateral extracavitary approach to the spine.
AB  - The development of alternative approaches to spine disorders marked an
      evolutionary change in the methods by which surgeons address diseases that affect
      the ventral portion of the spine. From the advent of spinal surgery until quite
      recently, physicians used posterior approaches almost exclusively for the
      treatment of all pathological processes. Surgeons subsequently became frustrated
      and disenchanted with outcomes of patients with anterior vertebral body disease
      when these procedures were applied. This sentiment is best reflected in the
      surgical thought related to Pott disease. In this paper, the authors chart the
      development of an influential approach to the spine that is designed to address
      these issues: the lateral extracavitary approach. They trace its origins to early
      precursor procedures and follow its use in current practice for the treatment of
      a variety of spinal disorders. They also examine its applications, role, and
      continued importance in the age of minimally invasive surgery.

PMID- 15264791
TI  - Minimally invasive spinal surgery: a historical perspective.
AB  - The concept of minimally invasive spinal surgery embodies the goal of achieving
      clinical outcomes comparable to those of conventional open surgery, while
      minimizing the risk of iatrogenic injury that may be incurred during the exposure
      process. The development of microscopy, laser technology, endoscopy, and video
      and image guidance systems provided the foundation on which minimally invasive
      spinal surgery is based. Minimally invasive treatments have been undertaken in
      all areas of the spinal axis since the 20th century. Lumbar disc disease has been
      treated using chemonucleolysis, percutaneous discectomy, laser discectomy,
      intradiscal thermoablation, and minimally invasive microdiscectomy techniques.
      The initial use of thoracoscopy for thoracic discs and tumor biopsies has
      expanded to include deformity correction, sympathectomy, vertebrectomy with
      reconstruction and instrumentation, and resection of paraspinal neurogenic
      tumors. Laparoscopic techniques, such as those used for appendectomy or
      cholecystectomy by general surgeons, have evolved into procedures performed by
      spinal surgeons for anterior lumbar discectomy and fusion. Image-guided systems
      have been adapted to facilitate pedicle screw placement with increased accuracy.
      Over the past decade, minimally invasive treatment of cervical spinal disorders
      has become feasible by applying technologies similar to those developed for the
      thoracic and lumbar spine. Endoscope-assisted transoral surgery, cervical
      laminectomy, discectomy, and foraminotomy all represent the continual evolution
      of minimally invasive spinal surgery. Further improvement in optics and imaging
      resources, development of biological agents, and introduction of instrumentation
      systems designed for minimally invasive procedures will inevitably lead to
      further applications in minimally invasive spine surgery.

PMID- 15264792
TI  - Retrospective analysis and modifications of retractor systems for anterior
      odontoid screw fixation.
AB  - The authors present an in-depth retrospective analysis of retractor systems for
      anterior odontoid screw fixation. They discuss various modifications and
      innovations of such systems and describe their own tubular retractor system, in
      which a beveled end conformal to the ventral surface of the vertebral column at
      the C2-3 level is introduced together with an incorporated light source. This new
      retractor system allows optimal anatomical exposure for controlled odontoid screw
      placement with improved protection of surrounding vital structures.

PMID- 15264793
TI  - History of the spinal cord localization.
AB  - The first reference to spinal cord injury is recorded in the Edwin Smith papyrus.
      Little was known of the function of the cord before Galen's experiments conducted
      in the second century AD. Galen described the protective coverings of the spinal
      cord: the bone, posterior longitudinal ligament, dura mater, and pia mater. He
      gave a detailed account of the gross anatomy of the spinal cord. During the
      medieval period (AD 700-1500) almost nothing of note was added to Galen's account
      of spinal cord structure. The first significant work on the spinal cord was that
      of Blasius in 1666. He was the first to differentiate the gray and white matter
      of the cord and demonstrated for the first time the origin of the anterior and
      posterior spinal nerve roots. The elucidation of the various tracts in the spinal
      cord actually began with demonstrations of pyramidal decussation by Mistichelli
      (1709) and Pourfoir du Petit (1710). Huber (1739) recorded the first detailed
      account of spinal roots and the denticulate ligaments. In 1809, Rolando described
      the substantia gelatinosa. The microtome, invented in 1824 by Stilling, proved to
      be one of the fundamental tools for the study of spinal cord anatomy. Stilling's
      technique involved slicing frozen or alcohol-hardened spinal cord into very thin
      sections and examining them unstained by using the naked eye or a microscope.
      With improvements in histological and experimental techniques, modern studies of
      spinal cord anatomy and function were initiated by Brown-Sequard. In 1846, he
      gave the first demonstration of the decussation of the sensory tracts. The
      location and direction of fiber tracts were uncovered by the experimental studies
      of Burdach (1826), Turck (1849), Clarke (1851), Lissauer (1855), Goll (1860),
      Flechsig (1876), and Gowers (1880). Bastian (1890) demonstrated that in complete
      transverse lesions of the spinal cord, reflexes below the level of the lesion are
      lost and muscle tone is abolished. Flatau (1894) observed the laminar nature of
      spinal pathways. The 20th century ushered in a new era in the evaluation of
      spinal cord function and localization; however, the total understanding of this
      remarkable organ remains elusive. Perhaps the next century will provide the
      answers to today's questions about spinal cord localization.

PMID- 15264794
TI  - A fluorogenic probe for the copper(I)-catalyzed azide-alkyne ligation reaction:
      modulation of the fluorescence emission via 3(n,pi)-1(pi,pi) inversion.
AB  - Chemoselective ligation reactions represent a powerful approach for labeling of
      proteins or small molecules in a biological environment. We report here a
      fluorogenic probe that is activated by click chemistry, a highly versatile bio
      orthogonal and chemoselective ligation reaction which is based on the azide
      moiety as the functional group. The electron-donating properties of the triazole
      ring that is formed in the course of the coupling reaction was effectively
      utilized to modulate the fluorescence output of an electronically coupled
      coumarin fluorophore. Under physiological conditions the probe is essentially
      nonfluorescent and undergoes a bright emission enhancement upon ligation with an
      azide. Time-resolved emission spectroscopy and semiempirical quantum-mechanical
      calculations suggest that the fluorescence switching is due to an inversion of
      the energy ordering of the emissive 1(pi,pi*) and nonemissive 3(n,pi*) excited
      states. The rapid kinetics of the ligation reaction render the probe attractive
      for a wide range of applications in biology, analytical chemistry, or material
      science.

PMID- 15264795
TI  - Sequence- and base-specific delivery of nitric oxide to cytidine and 5
      methylcytidine leading to efficient deamination.
AB  - Nitric oxide (NO) is an important endogenous regulatory molecule, and S
      nitrosothiols are believed to play a significant role in NO storage, transport,
      and delivery. On the basis of their ability to generate NO in vivo, S
      nitrosothiols can be used as therapeutic drugs. In this study, we have developed
      an innovative method for sequence- and base-specific delivery of NO to a specific
      site of DNA followed by specific deamination. We designed a NO transfer reaction
      from S-nitroso thioguanine to an imino tautomer of cytosine. Nitrosation of the
      thioguanosine-containing ODN 1 was carried out with S-nitroso-N
      acetylpenicillamine (SNAP) to produce ODN 2. An interstrand NO transfer reaction
      was performed using ODN 2 and its complementary ODN 3 having dC or dmC at the
      target site, and a rapid NO transfer reaction was observed. In contrast, a
      transfer reaction was not observed either with ODN 3 having dT, dA, or dG at the
      target site or with ODN 5-7 having dC at a nontarget site. In the analysis of
      deaminated products of the NO-transferred ODN 4, it was found that the
      transformation ratio from dmC to dT was as high as 42% together with the dmC
      diazoate (13%). In conclusion, we have demonstrated the innovative method of
      sequence- and base-specific delivery of nitric oxide to cytidine and 5
      methylcytidine. The selectivity and efficiency of NO transfer followed by
      deamination exhibited in this study are extremely high compared to those of the
      conventional methods.

PMID- 15264796
TI  - Double C-H activation during functionalization of phenyl(methyl)ketene on
      iridium(I) using alkynes. synthesis of 1,4-dien-3-ones.
AB  - Under the influence of an Ir(I) metal fragment, the methyl group of
      phenyl(methyl)ketene undergoes two C-H activations in reacting with internal
      alkynes, giving metallacycles 3 in 86-94% yield. Treatment of 3 with CO liberates
      1,4-dien-3-ones 5 in 81-93% yield, along with CO complex 4. A possible mechanism
      for the very selective double C-H activation-alkyne coupling is discussed.

PMID- 15264797
TI  - Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450
      catalyzed N-dealkylation.
AB  - Multiple oxidants have been implicated as playing a role in cytochrome P450
      mediated oxidations. Herein, we report results on N-dealkylation, one of the most
      facile reactions mediated by P450 enzymes. We have employed the N-oxides of a
      series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as
      both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic
      isotope effect profiles obtained using the N-oxide system were found to closely
      match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2
      system. The results are consistent with oxidation occurring solely through an
      iron-oxene species.

PMID- 15264798
TI  - Activation energies for the singlet excited state processes of substituted
      benzenes: para, meta, and ortho isomers of methylbenzonitrile and methylanisole
      in acetonitrile.
AB  - The rate constants of decay of the excited singlet states of the
      methylbenzonitriles (1-3) and the methylanisoles (4-6) have been determined by
      the measurement of fluorescence lifetimes over a broad range of temperatures (-45
      to +65 degrees C) in acetonitrile. By fitting this data to a nonlinear expression
      that includes the Arrhenius equation, rate constants for the activated process
      (reaction) and the unactivated ones (fluorescence and intersystem crossing) can
      be reliably obtained. Available literature data for benzene, toluene, and ortho
      xylene were also analyzed. The results indicate that the excited singlet state of
      substituted benzenes is quite reactive and forms a prefulvene biradical
      intermediate efficiently (quantum yield = 0.69 for benzene itself) by an
      activated route. In contrast, the efficiency of isolable product formation is
      quite low because the dominant process for this intermediate is returned to
      starting material. These observations explain why Ermolaev's rule does not apply
      to benzene derivatives.

PMID- 15264799
TI  - Site-directed electrostatic measurements with a thiol-specific ph-sensitive
      nitroxide: differentiating local pK and polarity effects by high-field EPR.
AB  - This communication describes the use of a methanethiosulfonate derivative of an
      imidazolidine nitroxide, methanethiosulfonic acid S-(1-oxyl-2,2,3,5,5-pentamethyl
      imidazolidin-4-ylmethyl) ester, IMTSL, for site-directed pKa determination of
      peptides by electron paramagnetic resonance. This spin label is covalently
      attached to the thiol group of unique cysteines incorporated into peptide
      structures. The tertiary amine nitrogen N3 of the label readily participates in
      proton exchange reactions, which are monitored through changes in EPR spectra of
      nitroxide moiety. Using EPR at 95 GHz (W-band) isotropic magnetic parameters of
      this nitroxide, both Aiso and giso, were calibrated in solvents of different
      polarity and pH. Two different linear correlations between Aiso and giso for
      acidic and basic forms of IMTSL were observed, making it possible to
      differentiate effects of local polarity from N3 protonation on nitroxide EPR
      spectra. Titration of a synthetic P11 peptide fragment of the laminin B1 chain
      illustrates the utility of this method.

PMID- 15264800
TI  - Generation of fullerenyl cation (EtO)2P+(OH)CH2-C60+ from RC60-H and from RC60
      C60R (R = CH2P(O)(OEt)2).
AB  - A novel fullerenyl cation (EtO)2P+(OH)CH2-C60+ was generated by simply dissolving
      the monofunctionalized hydrofullerene RC60-H or singly bonded dimer RC60-C60R (R
      = CH2P(O)(OEt)2) in oxidizing acids such as H2SO4 and FSO3H. The cation was also
      formed in CH2Cl2 by one-electron oxidation with aminium radical cation and was
      used for further functionalization of C60.

PMID- 15264801
TI  - Enantioselective synthesis of quaternary stereocenters via a catalytic asymmetric
      Stetter reaction.
AB  - A new electron-deficient chiral triazolium salt has been shown to catalyze the
      formation of quaternary stereocenters by an asymmetric intramolecular Stetter
      reaction. Pentafluorophenyl substitution on an aminoindanol-derived catalyst
      affords tertiary ether, thioether, and quaternary stereocenters in typically
      greater than 90% ee and very good chemical yield. Aromatic and aliphatic
      aldehydes are equally competent substrates for this reaction. The reaction
      proceeds at room temperature under mild conditions to provide quaternary
      stereocenters with functional group relationships that are particularly difficult
      to access by other methods.

PMID- 15264802
TI  - The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6
      epimerase.
AB  - ADP-l-glycero-d-manno-heptose 6-epimerase (AGME, RfaD) is a bacterial enzyme that
      is involved in lipopolysaccharide biosynthesis and interconverts ADP-beta-l
      glycero-d-manno-heptose (ADP-l,d-Hep) with ADP-beta-d-glycero-d-manno-heptose
      (ADP-d,d-Hep). AGME is known to require a tightly bound NADP+ cofactor for
      activity and presumably employs a mechanism involving transient oxidation of the
      substrate. Four mechanistic possibilities are considered that involve transient
      oxidation at either C-7' ', C-6' ', or C-4' ' of the heptose nucleotide. In this
      contribution, the use of solvent isotope incorporation studies and alternate
      substrates provides strong evidence for a mechanism involving nonstereospecific
      oxidation/reduction directly at C-6' '. It was found that the epimerization
      proceeds without any detectable incorporation of solvent-derived deuterium or 18O
      isotope into the product. This argues against mechanisms involving either proton
      transfers at carbon or dehydration/rehydration events. In addition, the
      deoxygenated analogues, 7' '-deoxy-ADP-l,d-Hep and 4' '-deoxy-ADP-l,d-Hep, were
      both found to serve as substrates for the enzyme, indicating that oxidation at
      either C-7' ' or C-4' ' is not required for catalysis.

PMID- 15264803
TI  - Photochemical ligation of DNA conjugates through anthracene cyclodimer formation
      and its fidelity to the template sequences.
AB  - Anthracene readily forms photoadducts, anthracene dimers, and this
      photodimerization reaction has been well characterized. In general, however, the
      reaction requires close proximity and certain spatial alignment of both reaction
      partners. DNA could provide an ideal scaffold for accelerating the photocyclic
      addition. We synthesized a number of anthracene-DNA conjugates. The sequences of
      the conjugates, 5'AntODNn and 3'AntODNn (the length of methylene linkers: n = 3
      or 6), were designed to bind adjacent sequences of the template with the
      anthracene units directed such that they stacked with each other. The conjugates
      were only dimerized in the presence of the template by light irradiation. The
      efficiency was affected by one-base displacement in the template sequence.

PMID- 15264804
TI  - Microemulsion-based synthesis of titanium phosphate nanotubes via amine
      extraction system.
AB  - The first titanium phosphate nanotubes with alternating interlayer spacings have
      been successfully prepared and characterized. The synthesis is accomplished in a
      reverse microemulsion formed in an amine extraction system. TEM data from samples
      made after different times of reaction suggest a scrolling-formation mechanism.

PMID- 15264805
TI  - The second triannulenylene: tri-[8]annulenylene.
AB  - Room-temperature dehydrohalogenation of bromocyclooctatetraene (BrC8H7) with
      potassium tert-butoxide followed (after a couple of minutes) by alkali metal
      reduction was used to generate the anion radical of tri-[8]annulenylene [(C8H6*
      )3] in HMPA. EPR analysis reveals that the odd electron is primarily located in
      one of the three eight-membered ring systems, which is rendered planar. Excellent
      agreement was obtained between spin densities predicted by B3LYP/6-31G*
      calculations and those observed. The neutral tri-[8]annulenylene system has a
      propensity toward polymerization, but it can be isolated for NMR and mass
      spectral analysis via the I2 oxidation of the anion radical. The NMR analysis
      reveals that two of the eight-membered rings are bent above the plane of the
      benzene ring and the other is bent below. Tri-[6]annulenylene (triphenylene) is
      the only other known member of the triannulenylenes.

PMID- 15264806
TI  - Preparation and structural characterization of RuS2 nanoislands on Au(111).
AB  - Among all the transition metal sulfides, ruthenium sulfide (RuS2) has been shown
      to be the most active catalyst for the hydrodesulfuriztion processes. Using X-ray
      photoemission spectroscopy (XPS) and scanning tunneling microscopy (STM), we have
      found a novel approach for the preparation of RuS2 nanoislands on an Au(111)
      substrate. Chemical vapor deposition of Ru3(CO)12 leads to metallic Ru
      nanoclusters on the gold substrate. Although sulfidation has not been observed on
      extended Ru (0001) surface, Ru nanoclusters react with S2, forming ruthenium
      sulfide. While the majority of the sulfide is in the form of nanosized clusters
      that aggregate into clustered islands, a small fraction of the sulfide is seen as
      flat islands. When Ru3(CO)12 was deposited on a sulfur-modified gold substrate at
      elevated temperature, flat islands of ruthenium sulfide are formed exclusively.
      The flat islands are single-layer RuS2 nanocrystals with a (111) surface
      termination which exhibits an ordered array of sulfur vacancies. On such RuS2
      (111) surfaces, excess sulfur is stable at low temperature and induces surface
      reconstruction, and desorbs at high temperature. The RuS2(111)/Au system provides
      an excellent model system for ruthenium sulfide catalysts.

PMID- 15264807
TI  - Enzymatic resolution of chiral phosphinate esters.
AB  - The bacterial phosphotriesterase has been shown to catalyze the stereoselective
      hydrolysis of phosphinate esters. The wild-type enzyme preferentially hydrolyzes
      the SP-enantiomers of methyl phenyl p-X-phenylphosphinate esters by 3 orders of
      magnitude. The mutant enzyme, I106T/F132A/H254G/H257W, exhibits the opposite
      stereoselectivity and hydrolyzes the RP-enantiomer up to 30 times faster than the
      corresponding SP-enantiomer. The enantiomerically pure phosphinate esters,
      prepared from the kinetic resolution of racemic mixtures, can serve as the entry
      point for the chemoenzymatic preparation of P-chiral phosphines and phosphine
      oxides.

PMID- 15264808
TI  - Reactivity of secondary metallocene alkyls and the question of dormant sites in
      catalytic alkene polymerization.
AB  - The reactivity of [rac-(C2H4(1-indenyl)2)Zr(n-butyl)][MeB(C6F5)3] (4), [rac
      (C2H4(1-indenyl)2)Zr(sec-butyl)][MeB(C6F5)3] (5), and [rac-(C2H4(1
      indenyl)2)Zr(polypropenyl)][MeB(C6F5)3] with propene, ethene, and hydrogen was
      studied by low-temperature (<-40 degrees C) 1H and 13C NMR spectroscopy in
      toluene solutions. In contrast with previous suggestions that 2 degrees zirconium
      alkyl species such as 5 are dormant sites, these measurements demonstrate
      reactivity of 2 degrees zirconium alkyls with propene and ethene comparable to
      the 1 degrees zirconium alkyl species 4 and [rac-(C2H4(1
      indenyl)2)Zr(polypropenyl)][MeB(C6F5)3]. Because 2,1-insertion of propene is an
      infrequent event, these results preclude significant accumulation of catalyst in
      the form of 2 degrees zirconium alkyls for this metallocene and counterion. The
      reactivity of 5 with hydrogen is at least 2 orders of magnitude faster than other
      1 degrees zirconium alkyls. Such high reactivity accounts for the puzzlingly high
      fraction of butyl end groups in prior hydrooligomerization studies and implies
      that catalyst responsivity to H2 as a molecular weight control agent correlates
      with the regioselectivity of the catalyst.

PMID- 15264809
TI  - Fluorescent GTP-sensing in aqueous solution of physiological pH.
AB  - A new water-soluble imidazolium anthracene derivative not only differentiates two
      structurally similar compounds GTP and ATP but also acts as potential fluorescent
      chemosensors (as a quencher and an enhancer, respectively) for GTP and ATP in
      100% aqueous solution (pH = 7.4, 10 mM HEPES).

PMID- 15264810
TI  - Phase transition of a single lipid bilayer measured by sum-frequency vibrational
      spectroscopy.
AB  - In this communication, we demonstrate the first use of sum-frequency generation
      (SFG) vibrational spectroscopy to measure directly the phase transition
      temperature (Tm) of a single planar supported lipid bilayer (PSLB). Three
      saturated phospholipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2
      diheptadecanoyl-sn-glycero-3-phosphocholine (DHPC), and 1,2-distearoyl-sn-glycero
      3-phosphocholine (DSPC), were studied. Lipid bilayer films were prepared by the
      the Langmuir-Blodgett method at a surface pressure of 30 nN/m. The symmetric
      nature of the bilayer was used to determine the Tm of bilayers by measuring the
      intensity of the symmetric methyl stretch at 2875 cm-1 from the lipid fatty acid
      chains as a function of temperature. A maximum in the CH3 symmetric stretch
      transition was observed at the Tm of the lipid film due to the reduction of
      symmetry in the bilayer. The SFG measured Tm for DPPC, DHPC, and DSPC were 41.0
      +/- 0.4, 52.4 +/- 0.7, and 57.9 +/- 0.5 degrees C, respectively. These values
      correlate well with the literature values of 41.3 +/- 1.8, 49 +/- 3, and 54.5 +/-
      1.5 degrees C for DPPC, DHPC, and DSPC, respectively obtained by differential
      scanning calorimetry (DSC) of lipid vesicles in solution. The high degree of
      correlation between the SFG spectroscopic measurements and the DSC results
      suggests the Tm of these lipids is not significantly altered upon immobilization
      on a surface.

PMID- 15264812
TI  - Dipeptide binding in water by a de novo designed guanidiniocarbonylpyrrole
      receptor.
AB  - A new dipeptide receptor 9, which was designed de novo based on theoretical
      calculations, efficiently binds dipeptides in water with Kass > 104 M-1 by a
      combination of ion pairing and hydrogen bonds as can be shown by UV-titration and
      NMR experiments.

PMID- 15264811
TI  - Specific labeling of cell surface proteins with chemically diverse compounds.
AB  - The specific and covalent labeling of fusion proteins with synthetic molecules
      opens up new ways to study protein function in the living cell. Here we present a
      novel method that allows for the specific and exclusive extracellular labeling of
      proteins on the surfaces of live cells with a large variety of synthetic
      molecules including fluorophores, protein ligands, or quantum dots. The approach
      is based on the specific labeling of fusion proteins of acyl carrier protein with
      synthetic molecules through post-translational modification catalyzed by
      phosphopantetheine transferase. The specificity and versatility of the labeling
      should allow it to become an important tool for studying and manipulating cell
      surface proteins and for complementing existing approaches in cell surface
      engineering.

PMID- 15264813
TI  - The observation of superparamagnetic behavior in molecular nanowires.
AB  - Using the anionic precursor [(Tp)Fe(CN)3]-, a new one-dimensional Ising cyanide
      bridged chain, [(Tp)2FeIII2(CN)6Cu(CH3OH).2CH3OH]n, has been prepared. The
      crystal structure and magnetic studies demonstrate that it is a single-chain
      magnet and the blocking temperature is ca. 6 K.

PMID- 15264814
TI  - Attomolar sensitivity in bioassays based on surface plasmon fluorescence
      spectroscopy.
AB  - With the aid of a dextran matrix, the metal-induced fluorescence loss of bound
      fluorophores can be greatly reduced, and the distance dependence of the
      fluorescence yield could be largely convoluted. This is optimized for the limit
      of detection assessment of surface plasmon fluorescence spectroscopy. The model
      system was designed as a direct assay with mouse IgG covalently immobilized to
      the carboxymethyl dextran matrix of a CM5 sensor chip from Biacore. Time-resolved
      ultratrace detection of fluorophore (Alexa-Fluor 647)-labeled rabbit anti-mouse
      antibody down to 500 aM (10-18 M) was accomplished, corresponding to a binding
      rate of approximately 10 molecules mm-2 min-1.

PMID- 15264815
TI  - Reversible control of free energy and topography of nanostructured surfaces.
AB  - We describe a facile method for the formation of dynamic nanostructured surfaces
      based on the modification of porous anodic aluminum oxide with poly(N-isopropyl
      acrylamide) (PNIPAAm) via surface-initiated atom transfer radical polymerization.
      The dynamic structure of these surfaces was investigated by atomic force
      microscopy (AFM), which showed dramatic changes in the surface nanostructure
      above and below the aqueous lower critical solution temperature of PNIPAAm. These
      changes in surface structure are correlated with changes in the macroscopic
      wettability of the surfaces, which was probed by water contact angle
      measurements. Principal component analysis was used to develop a quantitative
      correlation between AFM image intensity histograms and macroscopic wettability.
      Such correlations and dynamic nanostructured surfaces may have a variety of uses.

PMID- 15264816
TI  - Interaction-controlled HPLC for block copolymer analysis and separation.
AB  - An interaction-controlled HPLC technique has been developed to analyze
      homopolymer precursors in block copolymer systems that are not easily identified
      by size exclusion chromatography (SEC) and to obtain block copolymers that are
      homopolymer-free and compositionally narrower than the as-synthesized ones. We
      demonstrate that a "single peak" in SEC does not necessarily mean that the block
      copolymers are free of homopolymers (due to limitations in the SEC analysis of
      block copolymers) and propose to employ the interaction-controlled HPLC strategy
      for rigorous analysis and purification of block copolymers in terms of their
      chemical heterogeneity.

PMID- 15264818
TI  - Catalytic enantioselective allylboration of ketones.
AB  - The first example of catalytic enantioselective allylboration and crotylboration
      of simple ketones is described. High enantioselectivity (up to 93% ee) was
      obtained using 3 mol % CuF-iPr-DuPHOS as a chiral catalyst and 4.5 mol %
      La(OiPr)3 as a cocatalyst. Mechanistic studies strongly suggested that the active
      nucleophile of the present reaction is an allylcopper, and that La(OiPr)3
      facilitates the generation of an active allylcopper from the allylboronate,
      without affecting the transition-state structure of the ketone allylation step.

PMID- 15264817
TI  - Differential binding of Mg2+, Zn2+, and Cd2+ at two sites in a hammerhead
      ribozyme motif, determined by 15N NMR.
AB  - A decamer duplex model of Domain II of the hammerhead ribozyme was synthesized
      with [8-13C-1,7,NH2-15N3]-guanosine at the known metal binding site, G10.1 and,
      for comparison, [2-13C-1,7,NH2-15N3]-guanosine at G16.2. The 15N NMR chemical
      shifts of the labeled N7s monitored during addition of Mg2+, Cd2+, and Zn2+
      showed the same preference for binding at G10.1 over G16.2 for each metal. These
      results demonstrate that 15N labeling can be used to evaluate the binding of
      different metals, including Mg2+, to a given nitrogen, as well as to compare the
      binding potential of different sites.

PMID- 15264819
TI  - An undoped, single-phase oxide photocatalyst working under visible light.
AB  - A novel photocatalyst, PbBi2Nb2O9 has been discovered that shows high activities
      for degradation of organic pollutants, generation of photocurrent, and water
      decomposition into O2 or H2, all under visible right irradiation (lambda >/= 420
      nm). This is the first example of an undoped, single-phase oxide photocatalyst
      that shows such reactivity. Its quantum yields are much higher than those for
      most of the previously reported materials, especially in water decomposition to
      generate oxygen (29%). Since it is an oxide, there is much less concern for
      stability under light irradiation.

PMID- 15264820
TI  - The direct amino acid-catalyzed asymmetric incorporation of molecular oxygen to
      organic compounds.
AB  - We have disclosed the direct catalytic incorporation of 1O2 to aldehydes. The
      unprecedented amino acid-catalyzed asymmetric alpha-oxidation of aldehydes with
      molecular oxygen or air proceeded with high chemoselectivity and was a direct
      entry for the synthesis of both enantiomers of terminal diols. The results
      demonstrated that simple amino acids accomplished catalytic asymmetric oxidations
      with molecular oxygen or air, which has previously been considered to be in the
      domain of enzymes and chiral transition-metal complexes. The efficiency of the
      catalytic process may warrant the existence of an ancient pathway for the
      synthesis of hydroxylated organic compounds.

PMID- 15264821
TI  - A new chiral Rh(II) catalyst for enantioselective [2 + 1]-cycloaddition.
      mechanistic implications and applications.
AB  - A novel chiral Rh(II) catalyst (1) is introduced for the [2 + 1]-cycloaddition of
      ethyl diazoacetate to terminal acetylenes and olefins with high
      enantioselectivity. The catalyst 1 consists of one acetate bridging group and
      three mono-N-triflyldiphenylimidazoline-2-one bidentate ligands (DPTI) spanning
      the Rh(II)-Rh(II) metallic center in a structure that was determined by single
      crystal X-ray diffraction analysis. A rational mechanism is advanced that
      provides a straightforward explanation for the enantioselectivity and absolute
      stereochemical course of the [2 + 1]-cycloaddition reactions. A key element in
      this explanation is the cleavage of one of the Rh-O bonds of the bridging acetate
      group in the intermediate Rh-carbene complex to form a new pentacoordinate Rh
      carbene complex (formally 1.5 valent Rh) that can undergo [2 + 2]-cycloaddition
      with the C-C pi-bond of the acetylenic or olefinic substrate. Reductive
      elimination of the resulting adduct affords the cyclopropene or cyclopropane
      product. The C2-symmetry of the two DPTI ligands orthogonal to the bridging
      acetate also contributes to the high observed enantioselectivity and mechanistic
      clarity. The catalyst 1, which functions effectively at 0.5 mol %, can be
      recovered efficiently for reuse. Its ready availability, robustness, and
      effectiveness suggest it as a useful addition to the list of practical chiral
      Rh(II) catalysts for synthesis.

PMID- 15264822
TI  - Mechanism for catechol ring-cleavage by non-heme iron extradiol dioxygenases.
AB  - The catalytic mechanism of the non-heme iron extradiol dioxygenases has been
      studied using hybrid density functional theory. These enzymes cleave a C-C bond
      outside the two hydroxyl groups of catechols, in contrast to the intradiol
      enzymes which cleave the C-C bond between these two groups. The chemical models
      used comprise about 70 atoms and include the first-shell ligands, two histidines,
      one glutamate, and one water, as well as some second-shell ligands, two
      histidines, one aspartate, and one tyrosine. Catechol is found to bind as a
      monoanion in agreement with experiments, while dioxygen is found to replace the
      water ligand. A spin-transition from the initial septet to a quintet state
      prepares the system for formation of a bridging peroxide with the catechol
      substrate. When the O-O bond is cleaved in the suggested rate-limiting step, a
      key substrate intermediate with partly radical and partly anionic character is
      formed. The partly anionic character is found to determine the selectivity of the
      enzyme. The results are compared to available experimental information and to
      previous studies.

PMID- 15264823
TI  - A simple method for improving protein solubility and long-term stability.
AB  - Increasing a protein concentration in solution to the required level, without
      causing aggregation and precipitation is often a challenging but important task,
      especially in the field of structural biology; as little as 20% of nonmembrane
      proteins have been found to be suitable candidates for structural studies
      predominantly due to poor protein solubility. We demonstrate here that
      simultaneous addition of charged amino acids L-Arg and L-Glu at 50 mM to the
      buffer can dramatically increase the maximum achievable concentration of soluble
      protein (up to 8.7 times). These amino acids are effective in preventing protein
      aggregation and precipitation, and they dramatically increase the long-term
      stability of the sample; additionally, they protect protein samples from
      proteolytic degradation. Specific protein-protein and protein-RNA interactions
      are not adversely affected by the presence of these amino acids. These additives
      are particularly suitable for situations where high protein concentration and
      long-term stability are required, including solution-state studies of
      isotopically labeled proteins by NMR.

PMID- 15264824
TI  - Interfacial nano-structuring of designed peptides regulated by solution pH.
AB  - The in-situ conformations of peptide layers formed from the adsorption of two
      different synthetic 15-mer peptides at the hydrophilic silicon oxide/aqueous
      solution interface have been determined using neutron reflectivity (NR). The
      first peptide is based on the native sequence of a protein-binding domain within
      a heteromeric transcriptional activator, HAP2, identified from yeast
      Saccharomyces cerevisiae, with tyrosine (Y) present at the 1st, 8th and 15th
      amino acid positions, hence we denote this YYY15. Substitution of tryptophan (W)
      at the same locations gives WWW15. Both peptides have alpha-helical structure in
      phosphate buffer, as determined by circular dichroism (CD) spectra. D(2)O was
      used as solvent in the NR experiments to highlight structural heterogeneity
      across the hydrogenated peptide layers. At pH 7, YYY15 was found to form a weakly
      adsorbed interfacial monolayer. However, the mutant WWW15 showed strong
      interfacial adsorption, with the interfacial layer characterized by a middle
      hydrophobic sublayer of 7-8 A with lower scattering length density and two almost
      symmetrical hydrophilic outer sublayers of 6-8 A with higher scattering length
      density, suggesting the formation of a "sideways-on" helical conformation. An
      increase in pH to 9 resulted in the improved packing within the interfacial layer
      with similar structure. However, decrease in pH to 5 reduced the interfacial
      adsorption, mainly due to the enhanced solubility of the peptides associated with
      the protonation of arginine (R) and lysine (K) groups and the decreasing
      concentration of divalent HPO(4)(2-) in the phosphate buffer. Subsequent
      assessment of the reversibility of adsorption showed that once the peptide layers
      were formed they did not desorb. These interfacial structures may provide
      feasible routes to interfacial nano-templating.

PMID- 15264825
TI  - Enantioselective DNA alkylation by a pyrrole-imidazole S-CBI conjugate.
AB  - Conjugates 12S and 12R of N-methylpyrrole (Py)-N-methylimidazole (Im) seven
      ringed hairpin polyamide with both enantiomers of 1,2,9,9a
      tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) were synthesized, and
      their DNA alkylating activity was examined. High-resolution denaturing gel
      electrophoresis revealed that 12S selectively and efficiently alkylated at one
      match sequence, 5'-TGACCA-3', in 450-bp DNA fragments. The selectivity and
      efficiency of the DNA alkylation by 12S were higher than those of the
      corresponding cyclopropapyrroloindole (CPI) conjugate, 11. In sharp contrast,
      another enantiomer, 12R, showed very weak DNA alkylating activity. Product
      analysis of the synthetic decanucleotide confirmed that the alkylating activity
      of 12S was comparable with 11 and that 12S had a significantly higher reactivity
      than 12R. The enantioselective reactivity of 12S and 12R is assumed to be due to
      the location of the alkylating cyclopropane ring of the CBI unit in the minor
      groove of the DNA duplex. Since the CBI unit can be synthesized from commercially
      available 1,3-naphthalenediol, the present results open up the possibility of
      large-scale synthesis of alkylating Py-Im polyamides for facilitating their use
      in future animal studies.

PMID- 15264826
TI  - Single molecule solvation and its effects on tautomeric equilibria in a self
      assembled capsule.
AB  - A self-assembled cylindrical capsule provides a nanoscale environment that
      affects keto-enol equilibria. The equilibrium constants for encapsulated beta
      ketoesters show values that differ by an order of magnitude from that of the free
      tautomers in solution. For complexes with a single, large encapsulated guest, the
      inner surfaces of the capsule and the seam of the hydrogen bonds influence the
      equilibrium between the encapsulated keto and enol forms. For complexes of
      smaller beta-ketoesters, the coencapsulated solvent influences the equilibria.
      The solvent reduces the space available and affects the positioning of the ester
      in the capsule.

PMID- 15264827
TI  - Mediation of conformationally controlled photodecarboxylations of chiral and
      cyclic aryl esters by substrate structure, temperature, pressure, and medium
      constraints.
AB  - An aryl alkanoate, 2,4,6-trimethylphenyl (S)-(+)-2-methylbutyrate, whose ester
      group has a chiral center alpha to the carbonyl carbon and in which photo-Fries
      rearrangements are blocked by methyl substituents, undergoes facile
      photodecarboxylation under a variety of conditions and with complete retention of
      configuration. In fact, the decarboxylation process has many of the attributes of
      a symmetry-allowed suprafacial [1,3]sigmatropic rearrangement. The process
      requires concerted extrusion of carbon dioxide in a spiro-lactonic transition
      state, which has been investigated using high level DFT and CIS calculations:
      thermally less stable s-cis conformers in the ground and excited singlet states
      play an important role in determining the competitive efficiency of the process.
      Conformational control has also been imposed by substrate structure, solvent
      interactions, temperature, and applying external pressure, as well as using
      constraining media such as cyclodextrins and polyethylene films. The results are
      correlated with steady-state and dynamic fluorescence measurements at various
      temperatures in order to investigate further degrees to which ground and excited
      singlet state conformations affect the different photoreactivity channels
      available to the aryl esters.

PMID- 15264828
TI  - Insights into photodissociation dynamics of benzamide and formanilide from ab
      initio calculations.
AB  - In the present study, the five lowest electronic states that control the UV
      photodissociation of formanilide and benzamide have been characterized using the
      complete active space self-consistent field theory. The mechanisms for the
      initial relaxation and subsequent dissociation processes have been determined on
      the basis of the calculated potential energy surfaces and their intersections. It
      was found that the S(1)/T(1)/T(2) three-surface intersection plays an important
      role in the photodissociation processes of benzamide. However, the dissociation
      behavior of formanilide and benzamide was found to be quite different from that
      for aliphatic amides. The present study provides several insights into the
      photodissociation dynamics of formanilide and benzamide.

PMID- 15264829
TI  - Delocalized carotenoid cations in relation to the soliton model.
AB  - A series of charge-delocalized carotenoid mono- and dications have been prepared
      by treatment of selected carotenoids with Bronsted and Lewis acids. The detailed
      structures of the carbocations were established by NMR studies in the temperature
      range from -10 to -20 degrees C. The general strategy for structure elucidation
      by NMR of several cationic components in a mixture is outlined. Bond type and
      regions of bond inversion were established, as well as the charge distribution,
      which was determined from the difference in (13)C chemical shift at each carbon.
      This method gave a more accurate estimate for the partial charges than by using
      the Spiesecke-Schneider relationship. The resulting charge distribution was used
      as models for the structure of charged solitons. These carotenoid cations have
      the most delocalized charge so far determined, and the monocations represent the
      first experimental structure determination of positively charged solitons. The
      soliton width determined here is in good agreement with the results of previous
      AM1 calculations.

PMID- 15264830
TI  - Charge separation in ground-state 1,2,4,5-tetra-substituted benzene derivatives.
AB  - The conditions required for a formal biradical to exist in a zwitterionic form in
      the ground state are discussed following the recent experimental observation of
      zwitterionic structure in the ground state of a quinoid molecule (di-tert-butyl
      derivative of 2,5-diamino-1,4-benzoquinonediimine, I). A unique characteristic of
      molecules of this class is the fact that they may be considered as being formed
      by the union of two radicals, each having an odd number of pi electrons. In the
      case of I, one fragment carries the two amino group having 7 pi electrons; it
      acts as the electron donor. The other fragment carries the two oxygen atoms
      (carrying 5 pi electrons) and acts as an electron acceptor. A model that predicts
      the properties of these systems is presented, based on previous work on non
      Kekule hydrocarbons(2,3) and on the electron donating and attracting properties
      of the donor and acceptor groups, respectively. The zwitterion is formed by an
      electron transfer leading to two subunits carrying 6 pi electrons each and may
      become more stable than the triplet biradical even in the gas phase (i.e., in the
      absence of an external field) if the ionization potential of the donor is small
      (of the order of 3-4 eV). In some cases solvation in a polar solvent is required
      to make the zwitterionic form the lowest energy species on the ground-state
      surface. The 'spacer' between the donor and acceptor groups (which need not be
      necessarily derived from an aromatic structure) can be varied and influences the
      overall dipole moment that is calculated in some cases to be quite large (over 20
      D in the gas phase).

PMID- 15264831
TI  - Water-soluble dendrimers as photochemical reaction media: chemical behavior of
      singlet and triplet radical pairs inside dendritic reaction cavities.
AB  - Water-soluble poly(alkyl aryl ether) dendrimers have been explored for their use
      as hosts of organic substrates in aqueous media. Prototypical photoreactions,
      namely, photo-Fries reaction of (a) 1-naphthyl benzoate and (b) 1-naphthyl phenyl
      ester and alpha-cleavage reaction of (a) dibenzyl ketones and (b) benzoin alkyl
      ethers, have been examined. We find that a dendritic microenvironment not only
      restricts the mobility of radical intermediates but also rigidly encapsulates the
      substrate, intermediates, and products from "leaking" to the bulk environment.
      Comparative studies of the same photoreactions in micellar media demonstrate that
      dendritic media offer much better constrainment than the micelles.

PMID- 15264832
TI  - Controlled polymer grafting on single clay nanoplatelets.
AB  - We report on the controlled chemical grafting of well-defined polymer chains onto
      individual montmorillonite-type clay nanoplatelets and the direct visualization
      of the formed hybrid material at the nanoscale level. Our approach is based on
      the use of a surfactant mixture that contains varying proportions of hydroxyl
      substituted alkylammonium and unsubstituted alkylammonium cations to exchange the
      initial Na(+) counterions of the natural montmorillonite. This allows for the
      exchange of Na(+) by a tunable amount of hydroxyl functions at the surface of the
      clays. Those functions are then derivatized into aluminum alkoxides in order to
      initiate the ring-opening polymerization of epsilon-caprolactone directly from
      the clay surface that was swollen in an organic solvent. Atomic force microscopy
      measurements on the resulting polymer-grafted nanoplatelets demonstrate the
      strong dependence of the coating of the individual clay particles with the
      composition of the surfactant mixture used for the cationic exchange. This allows
      for the generation of a range of morphologies varying from polymer islands
      distributed over the clay surface to homogeneous polymer layers thoroughly
      coating the platelets. Finally, the control that is achievable over the synthesis
      of this new family of organic-inorganic nanohybrid materials has been extended to
      the surface grafting of semicrystalline poly(epsilon-caprolactone)-poly(lactic
      acid) diblock copolymers with defined compositions.

PMID- 15264833
TI  - Tetrafluoroborate salts as site-selective promoters for sol-gel synthesis of
      mesoporous silica.
AB  - Tetrafluoroborate ion (BF(4)(-)) serves as a powerful and better-behaved promoter
      than fluoride ion (F(-)) for hydrolytic condensation of alkoxysilanes, such as
      tetraethoxy orthosilicate, in aqueous media containing amphiphiles with onium ion
      headgroups as templates, affording thermally and hydrothermally stable mesoporous
      silica. According to (19)F NMR spectral profiles, BF(4)(-) is localized on a
      positive-charged micellar surface, thereby allowing a site-selective growth of
      the silica framework. The resulting porous silica has an ordered hexagonal
      structure with a well-developed and thick silicate wall. Even without
      calcination, the condensation with BF(4)(-) as the promoter progresses to a large
      extent to furnish a [Si(OSi-)(4)]/([HOSi(OSi-)(3)] + [(HO)(2)Si(OSi-)(2)]) ratio
      of 6.2, which is greater than that of mesoporous silica formed without BF(4)(-)
      before (1.5) and even after calcination (3.5) to promote thermal condensation in
      the solid state.

PMID- 15264834
TI  - Tracing kinetic intermediates during ligand binding.
AB  - Specific protein-ligand interactions are central to biological control. Although
      structure determination provides important insight into these interactions, it
      does not address dynamic events that occur during binding. While many biophysical
      techniques can provide a global view of these dynamics, NMR can be used to derive
      site-specific dynamics at atomic resolution. Here we show how NMR line shapes can
      be analyzed to identify long-lived kinetic intermediates for individual amino
      acids on the reaction pathway for a protein-ligand interaction. Different ligands
      cause different intermediate states. The lifetimes of these states determine the
      specificity of binding. This novel approach provides a direct, site-specific
      visualization of the kinetic mechanism of protein-ligand interactions.

PMID- 15264835
TI  - Imaging the binding ability of proteins immobilized on surfaces with different
      orientations by using liquid crystals.
AB  - We report an investigation of the binding ability of a protein immobilized on
      surfaces with different orientations but in identical interfacial
      microenvironments. The surfaces present mixed self-assembled monolayers (SAMs) of
      11-[19-carboxymethylhexa(ethylene glycol)]undecyl-1-thiol, 1, and 11
      tetra(ethylene glycol) undecyl-1-thiol, 2. Whereas 2 is used to define an
      interfacial microenvironment that prevents nonspecific adsorption of proteins, 1
      was activated by two different schemes to immobilize ribonuclease A (RNase A) in
      either a preferred orientation or random orientations. The binding of the
      ribonuclease inhibitor protein (RI) to RNase A on these surfaces was
      characterized by using ellipsometry and the orientational behavior of liquid
      crystals. Ellipsometric measurements indicate identical extents of immobilization
      of RNase A via the two schemes. Following incubation of both surfaces with RI,
      however, ellipsometric measurements indicate a 4-fold higher binding ability of
      the RNase A immobilized with a preferred orientation over RNase A immobilized
      with a random orientation. The higher binding ability of the oriented RNase A
      over the randomly oriented RNase A was also apparent in the orientational
      behavior of nematic liquid crystals of 4-cyano-4'-pentylcyanobiphenyl (5CB)
      overlayed on these surfaces. These results demonstrate that the orientations of
      proteins covalently immobilized in controlled interfacial microenvironments can
      influence the binding activities of the immobilized proteins. Results reported in
      this article also demonstrate that the orientational states of proteins
      immobilized at surfaces can be distinguished by examining the optical appearances
      of liquid crystals.

PMID- 15264836
TI  - Elastic properties of single amylose chains in water: a quantum mechanical and
      AFM study.
AB  - Recent single-molecule atomic force microscopy (AFM) experiments have revealed
      that some polysaccharides display large deviations from force-extension
      relationships of other polymers which typically behave as simple entropic
      springs. However, the mechanism of these deviations has not been fully
      elucidated. Here we report the use of novel quantum mechanical methodologies, the
      divide-and-conquer linear scaling approach and the self-consistent charge density
      functional-based tight binding (SCC-DFTB) method, to unravel the mechanism of the
      extensibility of the polysaccharide amylose, which in water displays particularly
      large deviations from the simple entropic elasticity. We studied the deformations
      of maltose, a building block of amylose, both in a vacuum and in solution. To
      simulate the deformations in solution, the TIP3P molecular mechanical model is
      used to model the solvent water, and the SCC-DFTB method is used to model the
      solute. The interactions between the solute and water are treated by the combined
      quantum mechanical and molecular mechanical approach. We find that water
      significantly affects the mechanical properties of maltose. Furthermore, we
      performed two nanosecond-scale steered molecular dynamics simulations for single
      amylose chains composed of 10 glucopyranose rings in solution. Our SCC-DFTB/MM
      simulations reproduce the experimentally measured force-extension curve, and we
      find that the force-induced chair-to-boat transitions of glucopyranose rings are
      responsible for the characteristic plateau in the force-extension curve of
      amylose. In addition, we performed single-molecule AFM measurements on
      carboxymethyl amylose, and we found that, in contrast to the results of an
      earlier work by others, these side groups do not significantly affect amylose
      elasticity. By combining our experimental and modeling results, we conclude that
      the nonentropic elastic behavior of amylose is governed by the mechanics of
      pyranose rings themselves and their force-induced conformational transitions.

PMID- 15264837
TI  - Two-dimensional crystallization: self-assembly, pseudopolymorphism, and symmetry
      independent molecules.
AB  - The self-assembly of a series of 1,3-disubstituted benzenes has been scrutinized
      by scanning tunneling microscopy (STM) and computational modeling. Small changes
      in the functional groups (e.g., ester, thioester, ketone) resulted in dramatic
      changes in packing patterns. Remarkably, several of the molecules gave rise to
      monolayers with more than one molecule in the asymmetric unit and displayed
      multiple packing patterns. This constitutes the most complex behavior observed to
      date in this type of monolayer and illuminates several issues of importance in
      three-dimensional crystallization. Intermolecular interactions associated with
      the observation of multiple molecules in the asymmetric unit and stabilization of
      pseudopolymorphs were identified. The geometry and electrostatic properties of
      the isolated molecule and monolayer density were found to be critical in
      determining which packing motif was adopted.

PMID- 15264838
TI  - Steric retardation of SN2 reactions in the gas phase and solution.
AB  - The gas-phase S(N)2 reactions of chloride with ethyl and neopentyl chlorides and
      their alpha-cyano derivatives have been explored with B3LYP, CBS-QB3, and
      PDDG/PM3 calculations. Calculations predict that the steric effect of the tert
      butyl group raises the activation energy by about 6 kcal/mol relative to methyl
      in both cases. Solvent effects have been computed with QM/MM Monte Carlo
      simulations for DMSO, methanol, and water, as well as with a polarizable
      continuum model, CPCM. Solvents cause a large increase in the activation energies
      of these reactions but have a very small differential effect on the ethyl and
      neopentyl substrates and their cyano derivatives. The theoretical results
      contrast with previous conclusions that were based upon gas-phase rate
      measurements.

PMID- 15264839
TI  - Catalytic oligomerization of ethylene to higher linear alpha-olefins promoted by
      the cationic group 4 [(eta 5-Cp-(CMe2-bridge)-Ph)MII(ethylene)2]+ (M = Ti, Zr,
      Hf) active catalysts: a density functional investigation of the influence of the
      metal on the catalytic activity and selectivity.
AB  - A detailed theoretical analysis is presented of the catalytic abilities of
      heavier group 4 (M = Zr, Hf) metals for linear ethylene oligomerization with the
      cationic [(eta(5)-C(5)H(4)-(CMe(2)-bridge)-C(6)H(5))M(IV)(CH(3))(2)](+) complex
      as precatalyst, employing a gradient-corrected DFT method. The parent Ti system
      has been reported as a highly selective catalyst for ethylene trimerization. The
      mechanism involving metallacycle intermediates, originally proposed by Briggs and
      Jolly, has been supported by the present study to be operative for the
      investigated class of group 4 catalysts. Metallacycle growth through bimolecular
      ethylene uptake and subsequent insertion is likely to occur at uniform rates for
      larger cycles that are furthermore comparable for Ti, Zr, and Hf catalysts.
      Ethylene insertion into the two smallest five- and seven-membered cycles is found
      to become accelerated for Zr and Hf catalysts, which is due to geometrical
      factors. In contrast, electronic effects act to raise the barrier for
      metallacycle decomposition, affording alpha-olefins upon descending group 4. This
      process is furthermore predicted to be kinetically more difficult for larger
      metallacycles. The oligomer distribution of the Zr-mediated reaction is likely to
      comprise predominantly 1-hexene together with 1-octene, while 1-butene and alpha
      olefins of chain lengths C(10)-C(18) should occur only in negligible portions. A
      similar composition of alpha-olefins having C(6)-C(18) chain lengths is indicated
      for the Hf catalysts, but with long-chain oligomers and polymers as the prevalent
      fraction. Between the group 4 catalysts of the investigated type, the Zr system
      appears as the most promising candidate having catalytic potential for production
      of 1-octene, although not selectively. The influence of temperature to modulate
      the oligomer product composition has been evaluated.

PMID- 15264840
TI  - Characterization of superparamagnetic "core-shell" nanoparticles and monitoring
      their anisotropic phase transition to ferromagnetic "solid solution" nanoalloys.
AB  - The structure, magnetism, and phase transition of core-shell type CoPt
      nanoparticles en route to solid solution alloy nanostructures are systematically
      investigated. The characterization of Co(core)Pt(shell) nanoparticles obtained by
      a "redox transmetalation" process by transmission electron microscopy (TEM) and,
      in particular, X-ray absorption spectroscopy (XAS) provides clear evidence for
      the existence of a core-shell type bimetallic interfacial structure. Nanoscale
      phase transitions of the Co(core)Pt(shell) structures toward c-axis compressed
      face-centered tetragonal (fct) solid solution alloy CoPt nanoparticles are
      monitored at various stages of a thermally induced annealing process and the
      obtained fct nanoalloys show a large enhancement of their magnetic properties
      with ferromagnetism. The relationship between the nanostructures and their
      magnetic properties is in part elucidated through the use of XAS as a critical
      analytical tool.

PMID- 15264841
TI  - Is the allylpalladium structure altered between solid and solutions?
AB  - Recent EXAFS measurements on
      [(Ph(2)PCH(2)CH(2)PPh(2))Pd(H(2)CCHCMe(2))]O(3)SCF(3) (Tromp et al. J. Am. Chem.
      Soc. 2002, 124, 14814) were interpreted as evidence that, when the complex is
      dissolved in THF, the allyl ligand adopts an eta(2) structure with a dangling
      allyl CH(2) substituent. DFT calculations of the Pd complex using H(2)P
      CH(2)CH(2)-PH(2) as a model for Ph(2)P-CH(2)CH(2)-PPh(2) (dppe), in the absence
      or the presence of the triflate counteranion, and modeling the THF solvent by
      explicit Me(2)O molecules or by a continuum model give always a conventional
      eta(3)-H(2)CCHCMe(2) structure with equal Pd-C bonds to the terminal carbon
      centers of the allyl. QM/MM calculations using the dppe ligand also fail to
      support an eta(2)-allyl structure as a global minimum. The EXAFS parameter space
      is shown to have multiple minima. These have very similar overall EXAFS, but have
      very different structural parameters. The minimum that was the basis for the
      previous structural conclusion gives a slightly better fit but has unrealistic
      Debye-Waller factors and threshold energies.

PMID- 15264842
TI  - Reversible disulfur monoxide (S2O)-forming retro-Diels-Alder reaction.
      disproportionation of S2O to trithio-ozone (S3) and sulfur dioxide (SO2) and
      reactivities of S2O and S3.
AB  - 5,6-Di-tert-butyl-2,3,7-trithiabicyclo[2.2.1]hept-5-ene 7-endo-oxide (4) was
      prepared by addition of S(2)Cl(2) to 3,4-di-tert-butylthiophene 1-oxide (3) in
      high yield. The oxidation of 4 with dimethyldioxirane gave a 7:1 isomeric mixture
      of 5,6-di-tert-butyl-2,3,7-trithiabicyclo[2.2.1]hept-5-ene 2-endo-7-endo-dioxide
      (5a) and 2-exo-7-endo-dioxide (5b) quantitatively. The thermally labile 5 was
      shown to undergo a retro-Diels-Alder reaction that produces S(2)O and 3 in a
      reversible way. The resulting S(2)O was trapped by Diels-Alder reactions with
      dienes to give 3,6-dihydro-1,2-dithiin 1-oxides in good yields. In the absence of
      the dienes, S(2)O disproportionates to SO(2) and S(3), and the resulting S(3)
      underwent a 1,3-dipolar cycloaddition with 3 on its syn-pi-face with respect to
      the S[double bond]O bond to give a trithiolane derivative, whereas in the
      presence of excess norbornene, it produced the 1,3-dipolar cycloadduct with
      norbornene in good yield. Thus, the retro-Diels-Alder reaction of 5 functions as
      an S(2)O and S(3) source. DFT calculations at the B3LYP/6-311+G(3df,2p) level
      were carried out in order to explain why S(2)O disproportionates to SO(2) and
      S(3) and why S(2)O acts as a dienophile and not a 1,3-dipole, whereas O(3) and
      S(3) serve as 1,3-dipoles.

PMID- 15264843
TI  - Effect of sodium sulfide on Ni-containing carbon monoxide dehydrogenases.
AB  - The structure of the active-site C-cluster in CO dehydrogenase from
      Carboxydothermus hydrogenoformans includes a mu(2)-sulfide ion bridged to the Ni
      and unique Fe, whereas the same cluster in enzymes from Rhodospirillum rubrum
      (CODH(Rr)) and Moorella thermoacetica (CODH(Mt)) lack this ion. This difference
      was investigated by exploring the effects of sodium sulfide on activity and
      spectral properties. Sulfide partially inhibited the CO oxidation activity of
      CODH(Rr) and generated a lag prior to steady-state. CODH(Mt) was inhibited
      similarly but without a lag. Adding sulfide to CODH(Mt) in the C(red1) state
      caused the g(av) = 1.82 EPR signal to decline and new features to appear,
      including one with g = 1.95, 1.85 and (1.70 or 1.62). Removing sulfide caused the
      g(av) = 1.82 signal to reappear and activity to recover. Sulfide did not affect
      the g(av) = 1.86 signal from the C(red2) state. A model was developed in which
      sulfide binds reversibly to C(red1), inhibiting catalysis. Reducing this adduct
      causes sulfide to dissociate, C(red2) to develop, and activity to recover. Using
      this model, apparent K(I) values are 40 +/- 10 nM for CODH(Rr) and 60 +/- 30
      microM for CODH(Mt). Effects of sulfide are analogous to those of other anions,
      including the substrate hydroxyl group, suggesting that these ions also bridge
      the Ni and unique Fe. This proposed arrangement raises the possibility that CO
      binding labilizes the bridging hydroxyl and increases its nucleophilic tendency
      toward attacking Ni-bound carbonyl.

PMID- 15264844
TI  - Aqueous cholesteric liquid crystals using uncharged rodlike polypeptides.
AB  - The aqueous, lyotropic liquid-crystalline phase behavior of the alpha-helical
      polypeptide, poly(N(epsilon)-2-[2-(2-methoxyethoxy)ethoxy]acetyl-lysine) (1), has
      been studied using optical microscopy and X-ray scattering. Solutions of
      optically pure 1 were found to form cholesteric liquid crystals at volume
      fractions that decreased with increasing average chain length. At very high
      volume fractions, the formation of a hexagonal mesophase was observed. The pitch
      of the cholesteric phase could be varied by a mixture of enantiomeric samples L-1
      and D-1, where the pitch increased as the mixture approached equimolar. The
      cholesteric phases could be untwisted, using either magnetic field or shear flow,
      into nematic phases, which relaxed into cholesterics upon removal of field or
      shear. We have found that the phase diagram of 1 in aqueous solution parallels
      that of poly(gamma-benzyl glutamate) in organic solvents, thus providing a useful
      system for liquid-crystal applications requiring water as solvent.

PMID- 15264845
TI  - Oxidative cyclizations: the asymmetric synthesis of (-)-alliacol A.
AB  - A tandem anodic coupling-Friedel-Crafts alkylation strategy has been used to
      rapidly complete the asymmetric synthesis of alliacol A. The anodic oxidation
      reaction allowed for the generation of a new bond between two nucleophiles. In
      the synthesis, the absolute stereochemistry of the final natural product is set
      relative to a methyl group that is incorporated early in the sequence using an
      asymmetric Michael reaction.

PMID- 15264846
TI  - Poly-L-lysine templated silicas: using polypeptide secondary structure to control
      oxide pore architectures.
AB  - Utilizing polypeptide secondary structure as a means for controlling oxide pore
      architectures is explored. Poly-L-lysine is used as a model polypeptide as its
      folding behavior is well understood and compatible with the sol-gel chemistry of
      silica. Here, we show that silicas synthesized with poly-L-lysine in a alpha
      helix conformation possess cylindrical pores that are approximately 1.5 nm in
      size, whereas silicas synthesized with poly-L-lysine in a beta-sheet conformation
      possess larger pores, the size of which are a function of the poly-L-lysine
      concentration, or in other words the size of the aggregate. In both cases, highly
      porous materials are obtained. In-situ circular dichroism measurements of the
      synthesis mixtures show that the poly-L-lysine secondary structure is not
      perturbed during synthesis. Infrared spectroscopy of the as-synthesized materials
      is consistent with the poly-L-lysine retaining its secondary structure. Grand
      canonical Monte Carlo simulations were also performed to validate the
      interpretation of the experimental adsorption results. The experimental isotherms
      are consistent with simulated isotherms of cylindrical pores 1.3-1.7 nm in size,
      in good agreement with expected values. Our results suggest a new avenue for
      synthesizing porous oxides with highly tuneable pore sizes and shapes under mild
      conditions.

PMID- 15264847
TI  - Nonaqueous and halide-free route to crystalline BaTiO3, SrTiO3, and (Ba,Sr)TiO3
      nanoparticles via a mechanism involving C-C bond formation.
AB  - A novel nonaqueous route for the preparation of nanocrystalline BaTiO(3),
      SrTiO(3), and (Ba,Sr)TiO(3) has been developed. In a simple one-pot reaction
      process, the elemental alkaline earth metals are directly dissolved in benzyl
      alcohol at slightly elevated temperatures. After the addition of Ti(O(i)Pr)(4),
      the reaction mixture is heated to 200 degrees C, resulting in the formation of a
      white precipitate. XRD measurements prove the exclusive presence of the
      perovskite phase without any other crystalline byproducts such as BaCO(3) or
      TiO(2). TEM investigations reveal that the BaTiO(3) nanoparticles are nearly
      spherical in shape with diameters ranging from 4 to 5 nm. The SrTiO(3) particles
      display less uniform particle shapes, and the size varies between 5 and 10 nm.
      Lattice fringes observed in HRTEM measurements further prove the high
      crystallinity of the nanoparticles. Surprisingly, GC-MS analysis of the reaction
      solution after hydrothermal treatment shows that hardly any ether formation
      occurs during the BaTiO(3) synthesis. Instead, the presence of 4-phenyl-2-butanol
      in stoichiometric amounts gives evidence that the formation mechanism proceeds
      mainly via a novel pathway involving C-C bond formation between benzyl alcohol
      and the isopropanolate ligand.

PMID- 15264848
TI  - Polyphosphate ions encapsulated in oxothiomolybdate rings: synthesis, structure,
      and behavior in solution.
AB  - Cyclic oxothiomolybdates containing polyphosphate ions were prepared by simple
      reactions in aqueous medium of the corresponding polyphosphate ions and the
      cyclic precursor K(2)I(2)Mo(10)S(10)O(10)(OH)(10)(OH(2))(5).15H(2)O.
      K(5)[Cl(P(2)O(7)]Mo(12)S(12)O(12)(OH)(12)(H(2)O)(4)].22H(2)O (1) was isolated
      from concentrated chloride solution (2.5 mol.L(-1)). 1 reveals a remarkable
      complex containing two different substrates encapsulated in a dodecanuclear ring,
      a H-bonded Cl(-) ion, and a covalently bonded [P(2)O(7)] group. The chloride ion
      in 1 can be selectively removed for a monohydrogenophosphate group yielding
      K(6)[(HPO(4))(P(2)O(7))Mo(12)S(12)O(12)(OH)(12)(H(2)O)(2)].19H(2)O (2), a mixed
      species containing a [P(2)O(7)] and a [HPO(4)] group. The substitution is
      accompanied by a significant change of the ring, which adopts a "pear-shape"
      conformation. In the presence of triphosphate ion, the "heart-shaped" decanuclear
      ring Rb(3)[(H(2)P(3)O(10))Mo(10)S(10)O(10)(OH)(10)].17.5H(2)O (3) is formed
      containing a linear [P(3)O(10)] group intimately embedded in the inorganic cyclic
      host. The three compounds were structurally characterized by single-crystal X-ray
      diffraction. The behaviors of 1, 2, and 3 in solution were studied by (31)P NMR.
      Variable temperature experiments, supported by a two-dimensional COSY (31)P
      experiment, revealed that the supramolecular interaction existing between the
      chloride ion and the ring in solid 1 is maintained in solution. Nevertheless, 1
      remains labile, and successive equilibria were evidenced and interpreted as an
      ion-pair association involving a halide ion (Cl, Br, or I), responsible for the
      conformational change of the [P(2)O(7)] group within the cavity. The influence of
      the nature of the halide guest (Cl(-), Br(-), and I(-)) on the successive
      equilibria was studied, and the thermodynamic constant related to the postulated
      equilibrium was determined. The stability of the supramolecular association
      decreases in the order Cl > Br > I. In solution, a phosphate exchange is observed
      for 2 while for 3 the absence of temperature dependence of the (31)P NMR spectrum
      confirms the conformation of the host-guest system is blocked. Elemental analysis
      and infrared characterizations are also supplied.

PMID- 15264849
TI  - Effect of ions on the vibrational relaxation of liquid water.
AB  - We study the relaxation of the O-H stretch vibration of water in aqueous salt
      solutions using femtosecond two-color pump-probe spectroscopy. The vibrational
      lifetimes are measured for a series of salts consisting of the anions Cl(-), Br(
      ), and I(-) and the cations Li(+), Na(+), and Mg(2+), for a range of
      concentrations from 0.5 M up to 6 M (chloride salts), 9 M (bromide salts), and 10
      M (iodide salts). In addition to the previously found dependence of the
      vibrational lifetime on the nature of the anion, the lifetime is found to depend
      on concentration and is observed to show a small but significant dependence on
      the nature of the cation. We present a model in which all the effects of ions on
      the vibrational relaxaton of liquid water are accounted for.

PMID- 15264850
TI  - Deep eutectic solvents formed between choline chloride and carboxylic acids:
      versatile alternatives to ionic liquids.
AB  - Deep Eutectic Solvents (DES) can be formed between a variety of quaternary
      ammonium salts and carboxylic acids. The physical properties are significantly
      affected by the structure of the carboxylic acid but the phase behavior of the
      mixtures can be simply modeled by taking account of the mole fraction of
      carboxylic acid in the mixture. The physical properties such as viscosity,
      conductivity, and surface tension of these DES are similar to ambient temperature
      ionic liquids and insight into the cause of these properties is gained using hole
      theory. It is shown that the conductivity and viscosity of these liquids is
      controlled by ion mobility and the availability of voids of suitable dimensions,
      and this is consistent with the fluidity of other ionic liquids and molten salts.
      The DES are also shown to be good solvents for metal oxides, which could have
      potential application for metal extraction.

PMID- 15264852
TI  - Poly(ethylene glycol)-supported enzyme inactivators. Efficient identification of
      the site of covalent attachment to alpha-chymotrypsin by PEG-TPCK.
AB  - A new methodology utilizing an enzyme inactivator covalently attached to
      poly(ethylene glycol) (PEG) is described in which the PEG affords facile and mild
      quantification, isolation, and identification of the site of enzyme inactivation.
      As proof of concept, the known affinity labeling agent for alpha-chymotrypsin, N
      tosyl-L-phenylalanine chloromethyl ketone (TPCK), was linked to PEG. The
      synthesis of the PEG-bound inactivator PEG-TPCK was carried out in good yields
      using standard solution-phase chemistry. Inactivation of alpha-chymotrypsin with
      PEG-TPCK was monitored via UV-vis spectroscopy in aqueous conditions, which
      resulted in less than 3% remaining activity, indicating that 97% of the alpha
      chymotrypsin was covalently modified with PEG-TPCK. The MALDI-TOF mass spectrum
      showed only one new peak that was distinct in shape and corresponded to the mass
      of PEG-TPCK-alpha-chymotrypsin. Following proteolytic digestion, the PEG-TPCK
      peptide was easily discernible from the rest of the digest in a HPLC trace
      because of its characteristic prolonged retention time and broad polymer shape.
      MALDI-TOF MS was used to determine the mass of the PEGylated peptide. Without
      prior removal of the PEG, the amino acid site to which PEG-TPCK covalently bound
      was determined via Edman sequencing. In comparison to other methods, the PEG
      supported inactivator system is significantly cheaper and safer than the
      synthesis of radiolabeled compounds; furthermore, isolation of the PEGylated
      peptide is milder and more selective than standard affinity binding columns.
      Edman sequencing provides an exact determination of the site of inactivator
      covalent attachment without extensive, tedious LC-MS analysis of a complex
      peptide mixture. The method described here could be applied to a variety of
      enzymes as an alternative to current techniques.

PMID- 15264853
TI  - Physicochemical and biological characterization of polyethylenimine-graft
      poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides
      and ribozymes.
AB  - Two different series of polyethylenimine (PEI) block copolymers grafted with
      linear poly(ethylene glycol) (PEG) were investigated as delivery systems for
      oligodeoxynucleotides (ODN) and ribozymes. The resulting interpolyelectrolyte
      complexes were characterized with respect to their physicochemical properties,
      protection efficiency against enzymatic degradation, complement activation, and
      biological activity under in vitro conditions. The effect of PEG molecular weight
      and the graft density of PEG blocks on complex characteristics was studied with
      two different series of block copolymers. The resulting ODN complexes were
      characterized by photon correlation spectroscopy (PCS) and laser Doppler
      anemometry (LDA) to determine complex size and zeta potential. Electrophoresis
      was performed to study the protective effects of the different block copolymers
      against enzymatic degradation of ODN. Intact ODN was quantified via densitometric
      analysis. Ribozymes, a particularly unstable type of oligonucleotides, were used
      to examine the influence of block copolymer structure on biological activity. The
      stabilization of ribozymes was also characterized in a cell culture model. Within
      the first series of block copolymers, the grafted PEG chains (5 kDa) had marginal
      influence on the complex size. Two grafted PEG chains were sufficient to achieve
      a neutral zeta potential. Within the second series, size and zeta potential
      increased with an increasing number of PEG chains. A high number of short PEG
      chains resulted in a decrease in complex size to values comparable to that of the
      homopolymer PEI 25 kDa and a neutral zeta potential, indicating a complete
      shielding of the charges. Complement activation decreased with an increasing
      number of short PEG 550 Da chains. Ribozyme complexes with PEG-PEI block
      copolymers achieved a 50% down-regulation of the target mRNA. This effect
      demonstrated an efficient stabilization and biological activity of the ribozyme,
      which was comparable to that of PEI 25 kDa. PEGylated PEI block copolymers
      represent a promising new class of drug delivery systems for ODN and ribozymes
      with increased biocompatibility and physical stability.

PMID- 15264854
TI  - Synthesis and characterization of bioconjugates of S-layer proteins.
AB  - The self-assembling proteins that form crystalline surface layers (S-layers) on
      many microbial species have found numerous applications due to their
      nanostructured nature. To devise a new method to construct surface displays that
      exploit S-layer self-assembly activity and nanostructural properties, we have
      constructed polymer bioconjugates of S-layer proteins. The conjugates formed are
      similar in function to the monomer alkanethiols that form self-assembled
      monolayers (SAMs) on gold surfaces. However, the self-assembly is driven by the
      protein "headgroup" that positions polymer-tethered endgroups on a surface. This
      paper examines the integration of protein purification, conjugation, and surface
      assembly that has led to the development of this new method for the formation of
      nanostructured surfaces. Purified S-layer proteins from Lactobacillus brevis were
      conjugated with small molecule probes and polymers using amine-based reactions.
      To keep multiple labeling of protein amine groups to acceptable levels, the
      conjugations were performed at pH 6.5, allowing for limited yields (24-39%) as
      determined by mass spectrometry and SDS-polyacrylamide gel electrophoresis. As
      the presence of high levels of unlabeled S-layer proteins is undesired, we have
      developed a protocol for further purification that employs monomeric avidin
      affinity chromatography. The surface self-assembly of the polymer bioconjugates
      onto amine-terminated microspheres was studied using epi-fluorescence, confocal,
      and scanning electron microscopy. The surfaces obtained exhibited homogeneous
      distributions of tethered molecules. Also, in cases where the modular assembly of
      two distinct types of tethered endgroups was accomplished, there was no evidence
      for phase separation in the surfaces. The modular assembly method will provide a
      potential route to controlling surface display density as the starting assembly
      conditions guide displayed endgroup concentrations in mixed molecular monolayers.

PMID- 15264855
TI  - De novo design of peptides with L-alpha-nucleobase amino acids and their binding
      properties to the P22 boxB RNA and its mutants.
AB  - A method to design novel molecules that specifically recognize a structured RNA
      would be a promising tool for the development of drugs or probes targeting RNA.
      In this study, the de novo design of the alpha-helical peptides having L-alpha
      amino acids with nucleobases (nucleobase amino acids, NBAs) was carried out.
      Binding affinities of the peptides for a hairpin RNA derived from P22 phage were
      dependent on the types and positions of the NBA units they have. Some NBA
      peptides bound to the wild-type RNA or its mutant with high affinity and high
      specificity compared with the native P22 N peptide. These results indicate that
      the NBA units on the peptides interact with the RNA bases in a specific manner.
      It is demonstrated that the de novo design of peptides with the NBA units is an
      effective way to construct novel RNA-binding molecules.

PMID- 15264856
TI  - Peptide-derivatized shell-cross-linked nanoparticles. 1. Synthesis and
      characterization.
AB  - The conjugation of the protein transduction domain (PTD) from the HIV-1 Tat
      protein to shell-cross-linked (SCK) nanoparticles is reported as a method to
      facilitate cell surface binding and transduction of SCK nanoparticles. Attaching
      increasing numbers of peptide sequences to SCK nanoparticles in a global solution
      state functionalization strategy has been devised as a method for increasing the
      efficiency of the cell-penetrating process. The numbers of peptides per SCK were
      controlled through stoichiometric balance and measured experimentally by two
      independent methods, UV-visible spectroscopy and phenylglyoxal analysis. PTD was
      conjugated in (0.005, 0.01, and 0.02) molar ratios, relative to the acrylic acid
      residues in the shell, to the SCK nanoparticles resulting in SCK populations
      possessing nominally 52, 104, and 210 (41, 83, and 202 as measured by
      phenylglyoxal analysis) PTD peptides per particle, respectively. The
      methodologies for the block copolymer and nanoparticle syntheses, peptide
      derivatization, and characterization of peptide-functionalized SCK nanoparticles
      are reported and the feasibility and efficiency of intracellular internalization
      of the respective SCKs were quantified.

PMID- 15264857
TI  - Peptide-derivatized shell-cross-linked nanoparticles. 2. Biocompatibility
      evaluation.
AB  - The conjugation of the protein transduction domain (PTD) from the HIV-1 Tat
      protein to shell cross-linked (SCK) nanoparticles is a method to facilitate cell
      surface binding and transduction. In the previous report, the preparation,
      derivatization, and characterization of peptide-functionalized SCK nanoparticles
      were reported in detail. Following assembly, the constructs were evaluated in
      vitro and in vivo to obtain a preliminary biocompatibility assessment. The
      effects of SCK exposure on cell viability were evaluated using a metabolic 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and a fluorescent
      apoptosis assay. Furthermore, stages of apoptosis were quantified by flow
      cytometry. Although higher levels of peptide functionalization resulted in
      decreased metabolic function as measured by MTT assay, significant apoptosis was
      not observed below 500 mg/L for all the samples. To evaluate the potential
      immunogenic response of the peptide-derivatized constructs, a real-time
      polymerase chain reaction (RT-PCR) system that allows for the in vitro analysis
      and quantification of the cellular inflammatory responses tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL1-beta) was utilized. The
      inflammatory response to the peptide-functionalized SCK nanoparticles as measured
      by RT-PCR show statistically significant increases in the levels of both TNF
      alpha and IL1-beta relative to tissue culture polystyrene (TCPS). However, the
      measured cytokine levels did not preclude the further testing of SCKs in an in
      vivo mouse immunization protocol. In this limited assay, measured increases in
      immunoglobulin G (IgG) concentration in the sera were minimal with no specific
      interactions being isolated, and more importantly, none of the mice (>50)
      subjected to the three 100 microg immunization protocol have died. Additionally,
      no gross morphological changes were observed in postmortem organ histology
      examinations.

PMID- 15264858
TI  - Combinatorial chemical reengineering of the alpha class glutathione transferases.
AB  - Previously, we discovered that human glutathione transferases (hGSTs) from the
      alpha class can be rapidly and quantitatively modified on a single tyrosine
      residue (Y9) using thioesters of glutathione (GS-thioesters) as acylating
      reagents. The current work was aimed at exploring the potential of this site
      directed acylation using a combinatorial approach, and for this purpose a panel
      of 17 GS-thioesters were synthesized in parallel and used in screening
      experiments with the isoforms hGSTs A1-1, A2-2, A3-3, and A4-4. Through
      analytical HPLC and MALDI-MS experiments, we found that between 70 and 80% of the
      reagents are accepted and this is thus a very versatile reaction. The range of
      ligands that can be used to covalently reprogram these proteins is now expanded
      to include functionalities such as fluorescent groups, a photochemical probe, and
      an aldehyde as a handle for further chemical derivatization. This site-specific
      modification reaction thus allows us to create novel functional proteins with a
      great variety of artificial chemical groups in order to, for example,
      specifically tag GSTs in biological samples or create novel enzymatic function
      using appropriate GS-thioesters.

PMID- 15264859
TI  - Pyridine-containing 6-hydrazinonicotinamide derivatives as potential bifunctional
      chelators for 99mTc-labeling of small biomolecules.
AB  - As a continuation of our interest in novel 99mTc chelating systems, several
      pyridine-containing HYNIC (6-hydrazinonicotinamide) derivatives (L1-L5) have been
      synthesized and characterized by NMR (1H and 13C) and LC-MS. 99mTc complexes of
      L1-L5 were prepared by the reaction of the HYNIC derivative with 99mTcO4- in the
      presence of excess tricine and stannous chloride. Results from this study show
      that the attachment site of the linker is critical for the formation of
      macrocyclic 99mTc complexes. For example, the pyridine-N in L3 is not able to
      bond to the Tc, because the lysine linker is attached to the 4-position. When the
      linker is at the 2-position, L1 forms the macrocyclic complex
      [99mTc(L1)(tricine)], but the radiochemical purity is relatively low. If the
      linker is attached to the 3-position of the pyridine ring, the HYNIC derivatives
      form macrocyclic complexes [99mTc(L)(tricine)] (L2, L4, and L5) in high yield
      (>95%). The HPLC data suggest that the macrocyclic complex [(99m)Tc(L2)(tricine)]
      exists in solution as four isomers: two diastereomers and two conformational
      isomers. Diastereomers are due to a combination of the chirality of the lysine
      linker and of the Tc chelate. Replacing lysine with a pentamethylenediamine
      linker results in the macrocyclic complex [99mTc(L4)(tricine)] with two
      conformational isomers, which interconvert rapidly at room temperature. Changing
      the linker from pentamethylenediamine to hexamethylenediamine did not eliminate
      the minor isomer; but the percentage of the minor isomer was reduced from
      approximately 10% for [99mTc(L4)(tricine)] to only 6% for [99mTc(L5)(tricine)].
      The linker length is an important parameter to minimize the minor isomer. LC-MS
      data of complexes [99mTc(L)(tricine)] (L2, L4, and L5) are completely consistent
      with their proposed compositions. On the basis of these data, it is concluded
      that pyridine-containing HYNIC derivatives have the potential as bifunctional
      chelators for 99mTc-labeling of small biomolecules if the linker is attached to
      the 3-position of the pyridine ring.

PMID- 15264860
TI  - Amphiphilic corroles bind tightly to human serum albumin.
AB  - Amphiphilic 2,17-bis-sulfonato-5,10,15(trispentafluorophenyl)corrole (2) and its
      Ga and Mn complexes (2-Ga and 2-Mn) form tightly bound noncovalent conjugates
      with human serum albumin (HSA). Protein-induced changes in the electronic
      absorption, emission, and circular dichroism spectra of these corroles, as well
      as results obtained from HPLC profiles of the conjugates and selective
      fluorescence quenching of the single HSA tryptophan, are interpreted in terms of
      multiple corrole:HSA binding sites. High-affinity binding sites, close to the
      unique tryptophan, are fully occupied at very low concentrations. At biologically
      relevant HSA concentrations (2-3 orders of magnitude larger than those employed
      in our studies), all corroles (2, 2-Ga, and 2-Mn) may be considered as fully
      conjugated.

PMID- 15264861
TI  - Reversible meso-scale smart polymer--protein particles of controlled sizes.
AB  - Functionalized beads and particles in the size range of tens to hundreds of
      nanometers (nano- to meso-scale) are finding increased applications in the
      bioanalytical field. We show here that conjugates of streptavidin and the
      temperature-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm), synthesized
      with low polydispersities by reversible addition--fragmentation chain transfer
      (RAFT) polymerization, rapidly formed mesoscale polymer--protein particles above
      the lower critical solution temperature (LCST). The average hydrodynamic
      diameters of these particles could be controlled between 250 nm to 900 nm by the
      choice of conjugate concentration and polymer molecular weight, and/or through
      control of the rate of temperature change. Once formed, the biohybrid particles
      were found to be stable for >16 h at the controlled size, unlike the free PNIPAAm
      which continued to aggregate and grow over time into very large and polydisperse
      aggregates. The reversibility between the smart polymer--protein particles and
      the free polymer--protein conjugates opens potential uses in traditional
      diagnostic formats and in microfluidic formats where the differential diffusive
      and physical properties might be exploited for separations, analyte
      concentration, and signal generation.

PMID- 15264862
TI  - A new triantennary galactose-targeted PEGylated gene carrier, characterization of
      its complex with DNA, and transfection of hepatoma cells.
AB  - Nonviral gene vectors remain inefficient in vivo largely because of their rapid
      clearance from the circulation and also their nonspecific association with the
      extracellular matrix. To overcome such drawbacks, cationic lipoplexes are now
      frequently coated with hydrophilic polymers such as PEGs to reduce nonspecific
      interactions, and ligands are also linked to their surface to obtain cell
      specific gene transfer. In view of the development of vectors for systemic gene
      delivery, we have designed and studied lipoplexes that carry a triantennary
      galactosyl ligand attached to the distal end of a (PEG)45-conjugated lipid. We
      incorporated this targeted PEGylated lipid into lipoplexes using two strategies
      of formulation, i.e., using either preformed micelles or liposomes. We
      demonstrated that the incorporation of PEG chains stabilized lipoplexes and
      masked, but only partially, the positive charges exposed on the surface of the
      particles. We have also shown that incorporation into lipoplexes of a lipidated
      PEG chain, bearing a ligand at its distal end, yielded particles that exhibited
      an accessible ligand throughout the whole range of cationic lipid to DNA ratios.
      We obtained a targeted transfection in HepG2 cells with one of the formulations.
      Our results strengthen the validity of using a ligand carried by a long PEG
      spacer arm for targeted gene transfer.

PMID- 15264863
TI  - Secondary mAb--vcMMAE conjugates are highly sensitive reporters of antibody
      internalization via the lysosome pathway.
AB  - Monoclonal antibodies (mAb) selectively recognizing tumor surface antigens are an
      important and evolving approach to targeted cancer therapy. One application of
      therapeutic mAbs is drug targeting via mAb-drug conjugate (ADC) technology.
      Identification of mAbs capable of internalizing following antigen binding has
      been accomplished by tracking decline of surface-bound mAb or by internalization
      of a secondary mAb linked to a toxin. These methods may not be sufficiently
      sensitive for screening nor wholly predictive of the mAbs' capacity for a
      specific drug delivery. We have developed a highly selective and sensitive method
      to detect mAbs for cell internalization and drug delivery. This system uses
      secondary anti-human or anti-murine mAbs conjugated to the high-potency drug
      monomethyl auristatin E (MMAE) via a highly stable, enzymatically cleavable
      linker. Prior studies of this drug linker technology demonstrated internalization
      of a primary ADC leads to trafficking to lysosomes, drug release by lysosomal
      cathepsin B, and ensuing cell death. A secondary antibody--drug conjugate (2
      degrees ADC) capable of binding primary mAbs bound to the surface of antigen
      positive cells has comparable drug delivery capability. The system is
      sufficiently sensitive to detect internalizing mAbs in nonclonal hybridoma
      supernatants and is predictive of the activity of subsequently produced primary
      ADC. Because of their high extracellular stability, the noninternalized 2 degrees
      ADC are 100--1000-fold less toxic to cells over extended periods of time,
      permitting an assay in which components can be added without need for separate
      wash steps. This homogeneous screening system is amenable to medium-throughput
      screening applications and enables the early identification of mAbs capable of
      intracellular trafficking for drug delivery and release.

PMID- 15264864
TI  - Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and
      cells: hole formation and the relation to transport.
AB  - We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with
      supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and
      KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays,
      flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7
      (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in
      diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did
      not initiate hole formation but expanded holes at existing defects. Acetamide
      terminated G5 PAMAM dendrimers did not cause hole formation in this concentration
      range. The interactions between PAMAM dendrimers and cell membranes were studied
      in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide
      terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However,
      the dose dependent release of the cytoplasmic proteins lactate dehydrogenase
      (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5
      PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the
      presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane
      integrity up to a 500 nM concentration. The induction of permeability caused by
      the amine-terminated dendrimers was not permanent, and leaking of cytosolic
      enzymes returned to normal levels upon removal of the dendrimers. The mechanism
      of how PAMAM dendrimers altered cells was investigated using fluorescence
      microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1)
      a hole formation mechanism is consistent with the observations of dendrimer
      internalization, (2) cytosolic proteins can diffuse out of the cell via these
      holes, and (3) dye molecules can be detected diffusing into the cell or out of
      the cell through the same membrane holes. Diffusion of dendrimers through holes
      is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into
      cells and is consistent with the lack of uptake of G5 acetamide-terminated PAMAM
      dendrimers.

PMID- 15264865
TI  - Synthetic bivalent CD4-mimetic miniproteins show enhanced anti-HIV activity over
      the monovalent miniprotein.
AB  - HIV-1 envelope glycoprotein gp120 is displayed as a trimeric complex on the
      surface of virion and infected T-cells, making it a typical multivalent target.
      This paper describes the design and synthesis of bivalent CD4-mimetic
      miniproteins to target the conserved CD4-binding pockets in the trimeric gp120.
      Using miniprotein CD4M9 as the model inhibitor, we created bivalent inhibitors in
      which two CD4M9 moieties were tethered by a spacer of varied length and evaluated
      their anti-HIV activity using a cell culture assay. The synthetic bivalent
      miniproteins showed 5-21-fold enhancement in anti-HIV activity over the
      monovalent miniprotein. The activity enhancement is dependent on the length of
      the spacer. The study suggests that targeting the oligomeric gp120 complex by
      novel multivalent ligands offers a valuable strategy for developing highly
      specific and effective HIV entry inhibitors.

PMID- 15264866
TI  - Design and synthesis of AX7574: a microcystin-derived, fluorescent probe for
      serine/threonine phosphatases.
AB  - The design and synthesis of AX7574, a microcystin-derived probe for
      serine/threonine phosphatases, is described. A key step in the synthesis was the
      conjugation under basic conditions of a tetramethylrhodamine 1,3-diketone
      derivative to the arginine side chain present in microcystin-LR. The resulting
      conjugate specifically labeled the active site of protein phosphatases 1 (PP-1)
      with a 1:1 stoichiometry and IC50 of 4.0 nM. AX7574 was used to isolate and
      identify PP-1, PP-2A, PP-4, and PP-6 in Jurkat cells. Finally, AX7574 was able to
      record changes in the phosphatase activity levels of calyculin A treated Jurkat
      cells versus untreated control cells.

PMID- 15264867
TI  - A liposomal system for contrast-enhanced magnetic resonance imaging of molecular
      targets.
AB  - Pegylated paramagnetic and fluorescent immunoliposomes were designed to enable
      the parallel detection of the induced expression of molecular markers on
      endothelial cells with magnetic resonance imaging (MRI) and fluorescence
      microscopy. MRI is capable of three-dimensional noninvasive imaging of opaque
      tissues at near cellular resolution, while fluorescence microscopy can be used to
      investigate processes at the subcellular level. As a model for the expression of
      a molecular marker, human umbilical vein endothelial cells (HUVEC) were treated
      with the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) to
      upregulate the expression of the adhesion molecule E-selectin/CD62E. E-selectin
      expressing HUVEC were incubated with pegylated paramagnetic fluorescently labeled
      liposomes carrying anti-E-selectin monoclonal antibody as a targeting ligand.
      Both MRI and fluorescence microscopy revealed the specific association of the
      liposomal MR contrast agent with stimulated HUVEC. This study suggests that this
      newly developed system may serve as a useful diagnostic tool to investigate
      pathological processes in vivo with MRI.

PMID- 15264868
TI  - Chemical conjugation of heterologous proteins on the surface of Cowpea mosaic
      virus.
AB  - Genetic economy leads to symmetric distributions of chemically identical subunits
      in icosaherdal and helical viruses. Modification of the subunit genes of a
      variety of viruses has permitted the display of polypeptides on both the
      infectious virions and virus particles made in expression systems. Icosahedral
      chimeric particles of this type often display novel properties resulting in high
      local concentrations of the insert. Here we report an extension of this concept
      in which entire proteins were chemically cross-linked to lysine and cysteine
      residues genetically engineered on the coat protein of icosahedral Cowpea mosaic
      virus particles. Three exogenous proteins, the LRR domain of internalin B, the T4
      lysozyme, and the Intron 8 gene product of the of the HER2 tyrosine kinase
      receptor were derivatized with appropriate bifunctional cross-linkers and
      conjugated to the virus capsid. Characterization of these particles demonstrated
      that (1) virtually 100% occupancy of the 60 sites was achieved; (2) biological
      activity (either enzyme or binding specificity) of the attached protein was
      preserved; (3) in one case (LRR-internalin B) the attached protein conformed with
      the icosahedral symmetry to the extent that a reconstruction of the derivatized
      particles displayed added density with a shape consistent with the X-ray
      structure of the attached protein. Strategies demonstrated here allow virus
      particle targeting to specific cell types and the use of an icosahedral virus as
      a platform for structure determination of small proteins at moderate resolution.

PMID- 15264869
TI  - Nuclear localization signal-targeted poly(ethylene glycol) conjugates as
      potential carriers and nuclear localizing agents for carboplatin analogues.
AB  - Carboplatin is a low-molecular-weight anticancer drug that acts by binding to the
      nuclear DNA of cells. Thus, efficient delivery of the platinum drugs to the
      nucleus of the cancer cells may enhance the cytotoxicity of the drug. Efficient
      drug delivery to the nucleus of cancer cells requires three levels of
      localization: targeting to the cancerous tissue, accumulation in the cancer
      cells, and intracellular localization in the nucleus. Nuclear localization
      signals (NLS) are short positively charged basic peptides that actively transport
      large proteins across the nuclear membrane. We have prepared conjugates in which
      the NLS is tethered to poly(ethyleneglycol)carboplatin conjugate (NLS-PEG-Pt) and
      compared their pharmacological properties to those of their untargeted analogues
      that do not possess the NLS (PEG-Pt). NLS-PEG-Pt conjugates are rapidly
      internalized into cancer cells and accumulate in the nucleus. Despite their rapid
      nuclear localization, they form less Pt-DNA adducts than the untargeted
      analogues, PEG-Pt, and are also less cytotoxic. These results support the
      hypothesis that carboplatin (unlike cisplatin) may require cytosolic activation
      prior to its binding to nuclear DNA.

PMID- 15264870
TI  - Novel polyamine-dialkyl phosphate conjugates for gene carriers. Facile synthetic
      route via an unprecedented dialkyl phosphate.
AB  - To develop a novel nonviral gene carrier, three types of polyamine-dialkyl
      phosphates conjugates were synthesized via an unprecedented synthetic
      intermediate, dimerized dicetyl phosphate (DCP) anhydride, and the transfection
      efficiency and the complexation properties of the conjugate-DNA were evaluated.
      Condensation of DCP by 1,3,5-triisopropylbenzenesulfonyl chloride, TPSCl, gives
      the dimerized anhydride, which is stable enough to isolate by column
      chromatography in approximately 90% yield. The anhydride is reactive with various
      amines, i.e., spermidine, spermine, and polyethylenimine (PEI(1800)), providing
      corresponding polyamine-DCP conjugates via phosphoramidate linkage. The polyamine
      DCP conjugates exhibited moderate transfection efficacy evaluated by beta
      galactosidase assay. The conjugate-DNA complex was observed by using an atomic
      force microscope (AFM), revealing that the PEI(1800)-DCP conjugate, which showed
      the most efficient transfection, enables the formation of the more compact
      complex with DNA.

PMID- 15264871
TI  - Cyclodextrin-modified polyethylenimine polymers for gene delivery.
AB  - Linear and branched poly(ethylenimines), lPEI and bPEI, respectively, grafted
      with beta-cyclodextrin are prepared to give CD-lPEI and CD-bPEI, respectively,
      and are investigated as in vitro and in vivo nonviral gene delivery agents. The
      in vitro toxicity and transfection efficiency are sensitive to the level of
      cyclodextrin grafting. The cyclodextrin-containing polycations, when combined
      with adamantane-poly(ethylene glycol) (AD-PEG) conjugates, form particles that
      are stable at physiological salt concentrations. PEGylated CD-lPEI-based
      particles give in vitro gene expression equal to or greater than lPEI as measured
      by the percentage of EGFP expressing cells. Tail vein injections into mice of 120
      microg of plasmid DNA formulated with CD-lPEI and AD-PEG do not reveal observable
      toxicities, and both nucleic acid accumulation and expression are observed in
      liver.

PMID- 15264872
TI  - Self-assembling nanocomplexes from insulin and water-soluble branched polyesters,
      poly[(vinyl-3-(diethylamino)- propylcarbamate-co-(vinyl acetate)-co-(vinyl
      alcohol)]-graft- poly(L-lactic acid): a novel carrier for transmucosal delivery
      of peptides.
AB  - The design of carriers for protein delivery that provide protection against
      enzymatic degradation and facilitate protein transport across epithelial
      surfaces, thus avoiding parenteral administration, remains a challenge. Self
      assembling nanoscale protein/polymer complexes might present a promising
      approach. We synthesized water-soluble, amphiphilic polyesters, poly[(vinyl-3
      (diethylamino)-propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft
      poly(L-lactic acid), containing a positively charged backbone, and studied the
      spontaneous formation of nanocomplexes (NC) with insulin. NC were characterized
      using dynamic light scattering, zeta-potential measurements, and atomic force
      microscopy (AFM). Insulin loading was determined with HPLC, and the binding
      constants were obtained by isothermal titration calorimetry (ITC). The NC
      formation was followed using nephelometric and light scattering techniques. Water
      soluble, positively charged, branched polyesters with amphiphilic properties were
      obtained in a three-step polymer-analogous reaction. The degree of amine
      substitution, DS, in the PVAL backbone was varied between 0.04 and 0.5, and
      grafting this backbone with L-lactide increased the molecular weight from 18 kDa
      to 81 kDa. The polymer composition was optimized to facilitate NC formation with
      insulin resulting in a DS of 0.09 and a poly(L-lactide) side chain substitution
      of 0.5 with an average chain length of two lactic acids. Depending on polymer
      composition, stable NC of 200-500 nm diameter were formed with insulin, and the
      binding constants ranged from 4.7 x 10(5) to 9.5 x 10(6) M(-1). Positively
      charged surface charges ranging from +5 to +35mV and an insulin loading up to 98%
      of 33 IU/mL were obtained. The NC visualized by AFM revealed spheroidal particles
      with an entangled internal structure. It was demonstrated that this class of
      multifunctional polymers is capable of self-assembly with a peptidic substrate.
      The resulting nanosized complexes offer the potential for mucosal insulin/protein
      delivery and merit further investigations under in vivo conditions.

PMID- 15264873
TI  - 99mTc-neolactosylated human serum albumin for imaging the hepatic
      asialoglycoprotein receptor.
AB  - 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA)-coupled neogalactosyl
      human serum albumin (GSA) is used as an imaging agent for asialoglycoprotein
      receptor of the liver. However, its labeling is inconvenient because it should be
      incubated for 30 min at 50 degrees C. In addition, the conjugated DTPAs can cause
      decrease of pI and denaturation of protein. Therefore, we developed an improved
      agent 99mTc-neolactosyl human serum albumin (LSA) which contains a terminal
      galactose. LSA was synthesized by conjugating lactose to human serum albumin by
      the formation of a Schiff's base and successive reduction with sodium
      cyanoborohydride. The number of conjugated lactose molecules per LSA was 40.7 +/-
      12.3. To simplify the labeling procedure, we used a direct labeling method that
      adopts a high affinity 99mTc binding site concept in antibody labeling. The
      produced LSA was reduced by beta-mercaptoethanol to generate sulfhydryl groups
      and purified by PD-10 size-exclusion column. The number of generated sulfhydryl
      groups per LSA was 21.9 +/- 3.0. Medronate and stannous chloride were added to
      the reduced LSA and freeze-dried. Finally, 99mTc-pertechnetate (37 MBq, 1 mL) was
      added to the vial and incubated for 10 min at room temperature. The labeling
      efficiency of 99mTc-LSA was higher than 98%, and the stability in human serum at
      37 degrees C for 24 h was over 90%. Biodistribution study using balb/c mice and
      imaging study using SD rats showed high initial liver uptake and slow increase in
      the intestine due to hepatobiliary excretion after metabolism in the hepatocytes.
      Negligible spleen uptake was found while 99mTc-tin colloid showed significant
      amount of spleen uptake due to reticuloendothelial uptake. In conclusion, an
      improved agent, 99mTc-LSA, for imaging asialoglycoprotein receptor of the liver
      was successfully developed which showed a simple labeling procedure, high
      labeling efficiency, high stability, and high initial liver uptake.

PMID- 15264874
TI  - Novel procedures for preparing 99mTc(III) complexes with tetradentate/monodentate
      coordination of varying lipophilicity and adaptation to 188Re analogues.
AB  - Improved methods are presented for the preparation of 99mTc and 188Re mixed
      ligand complexes with tetradentate and monodentate ligands of the general formula
      [MIII(Lm)(Ln)] (M = Tc, Re; Lm = NS3 or NS3COOH; Ln = isocyanide or phosphine).
      To avoid the undesired formation of reduced-hydrolyzed species of both metals,
      the preparation of complexes is performed in a two-step procedure. At first the
      Tc(III)- or Re(III)-EDTA complex is formed which reacts in a second step with the
      tripodal ligand 2,2',2' '-nitrilotris(ethanethiol) (NS3) or its carboxyl
      derivative NS3COOH (a) and the monodentate phosphine ligands (triphenylphosphine
      L1, dimethylphenylphosphine L2) or isocyanides (tert-butyl isonitrile L3,
      methoxyisobutyl isonitrile L4, 4-isocyanomethylbenzoic acid-L-arginine L5, 4
      isocyanomethylbenzoic acid-L-arginyl-L-arginine L6, 4-isocyanomethylbenzoic acid
      neurotensin(8-13) L7) to the so-called '4+1' complex. Copper(I) isocyanide
      complexes are used for preparing the '4+1' complexes. That facilitates storage
      stability and allows kit formulations, and, moreover, enables the formation of
      188Re complexes in acidic solution. Only micromolar amounts of the monodentate
      ligand are needed, and that results in high specific activity labeling of
      interesting molecules. The lipophilicity of complexes can be controlled by
      introducing a carboxyl group into the tetradentate ligand and/or derivatization
      of the monodentate ligands. Furthermore, the carboxyl group enables the
      conjugation of biomolecules. As an example, the neurotensin derivative CN-NT(8
      13) was prepared and labeled with 99mTc according to the '4+1' approach, and its
      behavior in vivo was studied.

PMID- 15264875
TI  - 99mTc-labeling and in vitro and in vivo evaluation of HYNIC- and (Nalpha
      His)acetic acid-modified [D-Glu1]-minigastrin.
AB  - Gastrin/CCK-2 receptors are overexpressed in a number of tumors such as medullary
      thyroid cancer (MTC) and small cell lung cancer (SCLC). Recently [D-Glu1]
      minigastrin (MG) has been radiolabeled with 131I, 111In, and 90Y and evaluated in
      patients. This study describes the labeling and evaluation of MG with technetium
      99m using two different labeling approaches: HYNIC as bifunctional coupling agent
      and (Nalpha-His)Ac as tridentate ligand for 99mTc(CO3) labeling. Labeling was
      perfomed at high specific activities using Tricine and EDDA as coligands for
      HYNIC-MG and [99mTc(OH2)3(CO)3]+ for (Nalpha-His)Ac-MG. Stability experiments
      were carried out by reversed phase HPLC analysis in PBS, serum, histidine, and
      cysteine solutions, as well as rat liver and kidney homogenates. Receptor binding
      and internalization experiments were performed using CCK-2 receptor positive
      AR42J rat pancreatic tumor cells. Biodistribution experiments were carried out in
      nude mice carrying AR42J tumors by injection of 99mTc-labeled peptide with or
      without coinjection of 50 microg of minigastrin I human (MGh). HYNIC-MG and
      (Nalpha-His)Ac-MG could be radiolabeled at high specific activities (>1
      Ci/micromol). For HYNIC-MG, high labeling yields (>95%) were achieved using
      Tricine and EDDA as coligands. Stability experiments of all 99mTc-labeled
      conjugates revealed a high stability of the label in PBS and serum as well as
      toward challenge with histidine and cysteine. Incubation in kidney homogenates
      resulted in a rapid degradation of all conjugates with <10% intact peptide after
      60 min at 37 degrees C, with no considerable differences between the radiolabeled
      conjugates; a somewhat lower degradation rate was seen in liver homogenates.
      Protein binding varied considerably with lowest levels for 99mTc-EDDA/HYNIC-MG.
      Competition experiments of unlabeled conjugates on AR42J membranes versus [125I
      Tyr12]-gastrin I showed high CCK-2 receptor affinity for all conjugates under
      study. Internalization behavior was very rapid for all radiolabeled conjugates in
      the order of 99mTc-(Nalpha-His)Ac-MG > 99mTc-EDDA/HYNIC-MG > 99mTc-Tricine/HYNIC
      MG. In tumor-bearing nude mice the highest tumor-uptake was observed with 99mTc
      EDDA/HYNIC-MG (8.1%ID/g) followed by 99mTc-Tricine/HYNIC-MG (2.2%ID/g) and 99mTc
      (Nalpha-His)Ac-MG (1.2%ID/g) which correlated with kidney uptake (101.0%ID/g,
      53.8%ID/g, 1.8%ID/g respectively). In this series of compounds 99mTc-EDDA/HYNIC
      MG with its very high tumor/organ ratios except for kidneys seems to be the most
      promising agent to target CCK-2 receptors. Despite promising properties
      concerning receptor binding, internalization, and in vitro stability, 99mTc
      (Nalpha-His)Ac-MG showed low tumor uptake in vivo.

PMID- 15264876
TI  - In vitro and in vivo comparison of human Escherichia coli heat-stable peptide
      analogues incorporating the 111In-DOTA group and distinct linker moieties.
AB  - Three human Escherichia coli heat-stable peptide (STh) analogues, each containing
      a DOTA chelating group, were synthesized by SPPS and oxidative refolding and
      compared in in vitro and in vivo systems. One analogue, DOTA-F19-STh(1-19),
      contains an N-terminal DOTA group attached via an amide bond linkage to an STh
      moiety which is essentially wild-type except for a Tyr to Phe alteration at
      position 19 of the molecule. A second analogue, DOTA-R1,4,F19-STh(1-19), differs
      from the first in that asparagine residues in positions 1 and 4 have been altered
      to arginine residues in order to examine the effect of positively charged groups
      in the linker domain. A third analogue, DOTA-11AUN-F19-STh(1-19), differs from
      the first in that it incorporates an 11-aminoundecanoic acid spacer group between
      the DOTA group and the first asparagine residue. In vitro competitive binding
      assays utilizing T-84 human colon cancer cells demonstrated that significant
      alterations to the N-terminal region of the STh molecule were well tolerated and
      did not significantly affect binding affinity of STh for the guanylyl cyclase C
      (GC-C) receptor. Internalization and efflux studies of the indium-labeled species
      demonstrated that inclusion of positive charge in the linker moiety inhibits
      internalization of the compound within tumor cells. The characteristics of the
      three analogues were compared in an in vivo model utilizing T-84 human colon
      cancer cell xenografts in SCID mice. Clearance of all analogues was rapid,
      primarily via renal excretion into the urine, with >89% ID excreted into the
      urine at 1 h pi for all analogues. The 111In-DOTA-R1,4,F19-STh(1-19) and 111In
      DOTA-11AUN-F19-STh(1-19) analogues both had longer residence times in the blood
      than did the 111In-DOTA-F19-STh(1-19) analogue, probably accounting for increased
      %ID/g values for tumors and nontarget tissues at 1 h pi. At 4 h pi, significant
      differences between analogues were only seen with respect to metabolic routes of
      excretion, indicating that increased blood residence time did not result in
      increased tumor residualization. Reduction of hepatic uptake of these compounds,
      however, could have significance in the development of agents for the imaging of
      hepatic metastases. The ability to manipulate in vivo pharmacodynamics and tumor
      uptake of radiolabeled STh peptides through modification of linker moieties is
      under continuing investigation in order to produce optimal imaging and
      therapeutic radiopharmaceuticals.

PMID- 15264877
TI  - A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of
      diethylenetriamine covalently bound to inulin, a potential macromolecular MRI
      contrast agent.
AB  - A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as
      contrast agent for magnetic resonance imaging (MRI) was synthesized. The
      structure of the chelate was derived from H5DTPA by replacing the central pendant
      arm by a phosphinic acid functional group, which was covalently bound to the
      polysaccharide inulin. On the average, each monosaccharide unit of the inulin was
      attached to approximately one (0.9) chelate moiety. The average molecular weight
      is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds
      the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate
      oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is
      completed by a water molecule. This compound shows promising properties for
      application as a contrast agent for MRI thanks to a favorable residence lifetime
      of this water molecule (170 ns at 298 K), a relatively long rotational
      correlation time (866 ps at 298 K), and the presence of two water molecules in
      the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward
      transmetalation with Zn(II) is as high as that of the clinically used
      [Gd(DTPA)(H2O)]2-.

PMID- 15264878
TI  - Solid-phase synthesis of multiantennary oligonucleotide glycoconjugates utilizing
      on-support oximation.
AB  - A novel method for preparation of multivalent oligonucleotide glycoconjugates on
      a solid support has been described. A pentaerythritol-based phosphoramidite (1)
      bearing two masked aminooxy groups has been used as the key building block. After
      conventional chain assembly, the aminooxy functions have been deblocked by a
      hydrazinium acetate treatment and subsequently oximated with fully acetylated 4
      oxobutyl alpha-D-mannopyranoside. The conjugates obtained have been shown to
      withstand standard ammonolytic deprotection and cleavage from the support. Four
      different oligonucleotide glycoconjugates containing two, four, or six alpha-D
      mannopyranosyl units (12-15) have been prepared to demonstrate the applicability
      of the procedure. The glycosyl residues only moderately retards hybridization of
      the oligonucleotide moiety.

PMID- 15264879
TI  - Toxicity of gold nanoparticles functionalized with cationic and anionic side
      chains.
AB  - The structure and properties of gold nanoparticles make them useful for a wide
      array of biological application. Toxicity, however, has been observed at high
      concentrations using these systems. MTT, hemolysis, and bacterial viability
      assays were used to explore differential toxicity among the cell types used,
      using 2 nm core particles. These studies show that cationic particles are
      moderately toxic, whereas anionic particles are quite nontoxic. Concentration
      dependent lysis mediated by initial electrostatic binding was observed in dye
      release studies using lipid vesicles, providing the probable mechanism for
      observed toxicity with the cationic MMPCs.

PMID- 15264880
TI  - Transfection with fluorinated lipoplexes based on new fluorinated cationic lipids
      and in the presence of a bile salt surfactant.
AB  - The synthesis of two fluorinated cationic lipids, which are analogues of
      frequently used synthetic gene carrier agents (including the cationic 2,3
      dioleoyloxy-N-[2-(spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminium
      (DOSPA) component of the commercially available liposomal Lipofectamine), and the
      disintegration and DNA accessibility (evaluated by the ethidium bromide (BET)
      intercalation assay) as well as the in vitro transfection efficacy of cationic
      lipoplexes formulated with these new lipids in conjunction with conventional or
      fluorinated helper lipids, in the absence or presence of sodium taurocholate
      (STC), a powerful anionic bile salt detergent, is reported. A higher stability,
      with respect to the STC lytic activity and DNA accessibility, of the fluorinated
      cationic lipoplexes as compared with their respective lipofectamine-based ones
      was demonstrated. Indeed, while the Lipofectamine lipoplexes were fully
      disintegrated at a [STC]/[lipid] molar ratio of 2000, only 40-60% of the DNA
      intercalation sites of the lipoplexes based on the fluorinated analogue of DOSPA
      were accessible to ethidium bromide. A higher transfection potential in the
      presence of STC was further found for the lipoplexes formulated with the
      fluorinated analogue of DOSPA as compared with the Lipofectamine preparation. For
      a STC concentration of 7.5 mM, lipofection mediated with these fluorinated
      lipoplexes was significantly higher (nearly 30- to 50-fold, p < 0.05) than with
      the Lipofectamine ones. These results confirm the remarkable transfection
      potential of fluorinated lipoplexes.

PMID- 15264881
TI  - Fluorescent vasotocin conjugate for identification of the target cells for brain
      actions of vasotocin.
AB  - The effects of neuropeptides on the brain are a major focus of neuroendocrine
      research, and little progress has been made in the identification of the target
      neurons for many neuropeptides. Arginine8-vasotocin (AVT) is a neurohypophyseal
      peptide present in nonmammalian vertebrates that controls many neural and
      behavioral functions. Here we describe synthesis and functional characterization
      of an AVT-Oregon green conjugate 1 (AVT-OG 1) that can be used in vivo to
      identify AVT target neurons. Application of AVT-OG 1 to the brainstem of an
      amphibian produces rapid, endosome-like internalization together with typical AVT
      like neurophysiological effects. Thus, preparation of AVT-OG 1, which preserves
      the peptide's neurophysiological effects, is useful as a fluorescent marker for
      AVT target neurons. Consequently, AVT-OG 1 conjugate will have considerable
      utility for analyzing the neural actions of AVT in the intact brain.

PMID- 15264882
TI  - Conjugation of a hairpin pyrrole-imidazole polyamide to a quinone methide for
      control of DNA cross-linking.
AB  - A series of quinone methide precursors designed for DNA cross-linking were
      prepared and conjugated to a pyrrole-imidazole polyamide for selective
      association to the minor groove. Although reaction was only observed for DNA
      containing the predicted recognition sequence, yields of strand alkylation were
      low. Interstrand cross-linking was more efficient than alkylation but still quite
      modest and equivalent to that generated by a comparable conjugate containing the
      N-mustard chlorambucil. Varying the length of the linker connecting the polyamide
      and quinone methide derivative did not greatly affect the yield of DNA cross
      linking. Instead, intramolecular trapping of the quinone methide intermediate by
      nucleophiles of the attached polyamide appears to be the major determinant that
      limits its reaction with DNA. Self-adducts of the quinone methide conjugate form
      readily and irreversibly as detected by a combination of chromatography and mass
      spectroscopy. This result is unlike comparable self-adducts observed for
      oligonucleotide conjugates that form more slowly and remain reversible.
      Equivalent intramolecular alkylation of a polyamide by its attached chlorambucil
      mustard was not observed under similar condition. The presence of DNA, however,
      did facilitate hydrolysis of this mustard conjugate.

PMID- 15264883
TI  - Carbohydrate conjugates for molecular imaging and radiotherapy: 99mTc(I) and
      186Re(I) tricarbonyl complexes of N-(2'-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose.
AB  - An approach to a new class of potential radiopharmaceuticals is demonstrated by
      the labeling of a glucosamine derivative with the tricarbonyls of 99mTc and
      186Re. The proligand HL2 (N-(2'-hydroxybenzyl)-2-amino-2-deoxy-D-glucose) was
      produced by hydrogenation of the corresponding Schiff base and reacted with
      [NEt4]2[Re(CO)3Br3] to form the neutral complex [(L2)Re(CO)3] in 40% yield. 1H
      and 13C NMR spectra indicate that the [Re(CO)3] core is bound in a tridentate
      fashion via the amino N, phenolato O, and C-3 hydroxyl O atoms of the ligand. At
      the tracer-level, labeling of HL2 with [99mTc(CO)3(H2O)3]+ and
      [186Re(CO)3(H2O)3]+ was achieved in aqueous conditions in 95 +/- 2% and 94 +/- 3%
      average radiochemical yields, respectively.

PMID- 15264884
TI  - Labeling of steroids on solid phase.
AB  - Up to four tetra-tert-butyl-1-[4
      aminoacetamido)benzyl]diethylenetriaminetetrakis(acetato) derivatives of Fmoc
      glutamic acid (1) were attached to two steroids (17alpha-hydroxyprogesterone-3-O
      carboxymethyloxime 2 and 1,3,5(10)-estratriene-3,16alpha,17beta-triol-6-one-6-O
      carboxymethyloxime, 3)) on solid phase using an oligopeptide synthesizer. Upon
      deprotection and conversion to the corresponding europium(III) chelates, these
      steroid conjugates were used in DELFIA-based competitive fluoroimmunoassays. The
      more chelates conjugated to 17-alpha-hydroxyprogesterone, the more diluted
      antiserum could be used in an immunoassay for 17-alpha-hydroxyprogesterone,
      without any alteration of the measurement range. Hence, 17-alpha
      hydroxyprogesterone tracers with several chelates are useful when a high serum
      dilution factor is desired i.e., when only a limited quantity of antiserum is
      available. The result demonstrates the suitability and usefulness of
      lanthanide(III) chelates as multilabels in bioaffinity assays.

PMID- 15264885
TI  - Synthesis and characterization of dextran-peptide-methotrexate conjugates for
      tumor targeting via mediation by matrix metalloproteinase II and matrix
      metalloproteinase IX.
AB  - We designed and synthesized new dextran-peptide-methotrexate conjugates for tumor
      targeted delivery of chemotherapeutics via the mediation of matrix
      metalloproteinase II (MMP-2) and matrix metalloproteinase IX (MMP-9), both being
      widely known tumor-associated enzymes. A robust and flexible synthesis procedure
      and process monitoring chromatography assays were developed. The linker chemistry
      and the backbone charge were optimized to allow high sensitivity of the
      conjugates toward the targeted enzymes. The optimal conjugate carries Pro-Val-Gly
      Leu-Ile-Gly as the peptide linker, and the charge on the dextran backbone is
      fully neutralized. In the presence of the targeted enzymes, the peptide was
      cleaved and peptidyl methotrexate was released, with a kcat/Km value of 1.21 x
      10(5) M(-1) s(-1) for MMP-2 and 3.60 x 10(3) M(-1) s(-1) for MMP-9, respectively.
      Satisfactory stability of the new conjugates was demonstrated in serum containing
      conditions, suggesting the conjugates can remain intact in systemic circulation.
      These findings supported the tumor targeting capability of the new conjugates and
      warranted further investigation with in vivo study.

PMID- 15264886
TI  - Bacteriorhodopsin conjugates as anchors for supported membranes.
AB  - The sophistication of supported lipid bilayer membranes has increased steadily as
      new applications are being explored. In general, tethered lipids are used to
      anchor the lipid bilayer to the substrate. Here we describe a new type of
      anchoring system for supported lipid bilayers that is based on biotin-PEG3400
      bacteriorhodopsin conjugates. Amine-based coupling was used to construct the
      polymer conjugates, followed by fluorophore labeling to enable confocal imaging.
      The bacteriorhodopsin-based anchoring system was used to construct solid
      supported vesicles from streptavidin-coated microspheres. This method could
      provide a new route for the stability enhancement of supported lipid bilayer
      membrane assemblies.

PMID- 15264887
TI  - Hapten and antibody production for a sensitive immunoassay determining a human
      urinary metabolite of the pyrethroid insecticide permethrin.
AB  - Permethrin is the most popular synthetic pyrethroid insecticide in agriculture
      and public health. For the development of the enzyme-linked immunosorbent assay
      (ELISA) to evaluate human exposure to permethrin, the glycine conjugate (DCCA
      glycine) of a major metabolite, cis/trans-3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane-1-carboxylic acid (DCCA), of permethrin was established as
      the target analyte. Four different types of the cis- and trans-isomers of
      immunizing haptens were synthesized as follows: N-(cis/trans-3-(2,2
      dichlorovinyl)-2,2-dimethylcyclopropane-1-carbonyl)glycine (hapten 3), N
      (cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carbonyl)-4-amino-l
      phenylalanine (hapten 5), N-(N-(cis/trans-3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane-1-carbonyl)glycine)amino-6-(2,4-dinitrophenyl)aminohexanoic
      acid (hapten 9), and N-(cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane
      1-carbonyl)glycine-4-oxobutanoic acid (hapten 24). Sixteen polyclonal antibodies
      produced against each cis- or trans-hapten-thyroglobulin conjugate as immunogens
      were screened against numerous hapten-bovine serum albumin conjugates as coating
      antigens. Six ELISAs with both a heterologous hapten structure and a heterologous
      hapten configuration (cis/trans or trans/cis) between antibody and coating
      antigen showed a high sensitivity for the target analyte. The IC50 was 1.3, 2.1,
      and 2.2 microg/L for the trans-target analyte and 0.4, 2.3, and 2.8 microg/L for
      the cis-target analyte. The immunizing haptens, except for hapten 5, provided the
      target specific antibodies. Molecular modeling of the haptens supported the
      selection of reasonable immunizing haptens that best mimicked the target analyte.
      Hapten 5 was suitable as a coating antigen rather than as an immunogen since it
      had a different geometry. Very low cross-reactivities were measured to
      permethrin, its free metabolite (DCCA), PBA-glycine conjugate, and glycine. The
      ELISA will be optimized for the detection of total cis/trans-DCCA-glycine in
      human urine samples.

PMID- 15264888
TI  - Analysis of flavonoids and other phenolic compounds using high-performance liquid
      chromatography with coulometric array detection: relationship to antioxidant
      activity.
AB  - High-performance liquid chromatography coupled with a coulometric array detector
      was used to characterize the electrochemical behavior of 17 flavonoids and three
      cinnamic acid derivatives. The antioxidant activity of these phenolic compounds
      was evaluated by the ferric reducing activity power (FRAP), the oxygen radical
      absorbance capacity (ORAC), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      assays. All flavonoids, except kaempferol-3-rutinoside, malvidin-3-glucoside, and
      peonidin-3-glucoside, had two oxidation potentials (100-300 and 700-800 mV).
      Quercetin and myricetin had an additional oxidation wave at 400 mV. The
      electrochemical responses at a relatively low oxidation potential (300 mV) and
      the cumulative responses at medium oxidation potentials (400 and 500 mV) had the
      highest correlations with antioxidant activities. The highest correlations
      between electrochemical characteristics and antioxidant activities were found
      between electrochemical responses and antioxidant activities obtained in the FRAP
      assay and in the DPPH assay after short reaction periods. Lower correlations were
      revealed between electrochemical responses and antioxidant activities obtained in
      the ORAC assay.

PMID- 15264889
TI  - Determination of phytic acid and inositol pentakisphosphates in foods by high
      performance ion chromatography.
AB  - A high-performance anion exchange chromatographic method was adapted for the
      quantitative determination of phytic acid and inositol pentakisphosphate isomers
      (excluding enantiomers) in foods. Because of the cost and limited availability of
      inositol phosphate standards, a phytic acid sodium salt standard was used for the
      calculation of an average relative response factor for the quantification of
      inositol pentakisphosphate isomers, and the purity of phytic acid sodium salt
      standard was also accurately established. The detection limits (S/N = 3) for
      phytic acid and inositol pentakisphosphates were in the range of 1.5-3.4 microM
      (0.1-0.2 microg/100 microL). This method has been successfully applied to the
      determination of phytic acid and inositol pentakisphosphates in a variety of
      beans and nuts after extraction with 0.5 M HCl and cleanup with solid phase
      extraction cartridges. The results demonstrated that there was a strong
      correlation between either the phytic acid content or the total content of phytic
      acid together with inositol pentakisphosphates and the total dietary fiber
      content in the group of all raw dry beans and in the group of raw dry black beans
      but not in the group of raw dry red kidney beans, which was probably due to the
      insufficient number of the raw dry red kidney bean samples.

PMID- 15264890
TI  - Accelerated solvent extraction and confirmatory analysis of sulfonamide residues
      in raw meat and infant foods by liquid chromatography electrospray tandem mass
      spectrometry.
AB  - This paper describes a new method for the rapid extraction and unequivocal
      confirmation of 13 sulfonamides (SAs) in raw meat and infant foods. The highly
      automated extraction procedure is based on accelerated solvent extraction
      followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a
      confirmatory analysis. After 1 g of food matrix was blended with 2 g of C18 as a
      solid support material, the mixture was packed into the extraction cell and the
      SAs were extracted with 10 mL of hot water at 160 degrees C and 100 atm; 100
      microL of the extract was directly injected into the LC-MS system. The analytes
      were ionized in an electrospray interface operating in the positive ion mode and
      were identified by selecting two multireaction monitoring transitions, which
      guaranteed method specificity. Typical recoveries from crude meat and baby food
      samples ranged from 70 to 101% at a fortification level of 100 ppb, corresponding
      to the maximum residue limits established by the European Union and the U.S. Food
      and Drug Administration. The interday method precision was less than 8.5%, and
      the limits of detection were below 2.6 ppb. This study has taken matrix-induced
      suppression of ionization into account, by comparing standard and matrix-matched
      calibration curves. Four of the 13 monitored SAs have been detected in some baby
      foods and raw meat samples, bought from Roman supermarkets and butchers' shops,
      using the described methodology.

PMID- 15264891
TI  - Improved sample preparation to determine acrylamide in difficult matrixes such as
      chocolate powder, cocoa, and coffee by liquid chromatography tandem mass
      spectroscopy.
AB  - An improved sample preparation (extraction and cleanup) is presented that enables
      the quantification of low levels of acrylamide in difficult matrixes, including
      soluble chocolate powder, cocoa, coffee, and coffee surrogate. Final analysis is
      done by isotope-dilution liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-MS/MS) using d3-acrylamide as internal standard. Sample
      pretreatment essentially encompasses (a) protein precipitation with Carrez I and
      II solutions, (b) extraction of the analyte into ethyl acetate, and (c) solid
      phase extraction on a Multimode cartridge. The stability of acrylamide in final
      extracts and in certain commercial foods and beverages is also reported. This
      approach provided good performance in terms of linearity, accuracy and precision.
      Full validation was conducted in soluble chocolate powder, achieving a decision
      limit (CCalpha) and detection capability (CCbeta) of 9.2 and 12.5 microg/kg,
      respectively. The method was extended to the analysis of acrylamide in various
      foodstuffs such as mashed potatoes, crisp bread, and butter biscuit and cookies.
      Furthermore, the accuracy of the method is demonstrated by the results obtained
      in three inter-laboratory proficiency tests.

PMID- 15264892
TI  - Development and comparison of four real-time polymerase chain reaction systems
      for specific detection and quantification of Zea mays L.
AB  - Four real-time polymerase chain reaction systems aiming at the specific detection
      and quantification of maize DNA are described. They have been developed in four
      independent laboratories targeting different maize sequences, i.e., alcohol
      dehydrogenase (Adh1), high mobility group protein (hmga), invertase A (ivr1), and
      zein, respectively. They were all fully specific, showing a very similar
      quantification accuracy along a number of distantly related maize cultivars and
      being either single or low copy number genes. They were highly sensitive and
      exhibited limits of quantification below 100 maize genomic copies. In
      consequence, they are considered suitable for use as maize specific endogenous
      reference genes in DNA analyses, including GMO quantitative tests.

PMID- 15264893
TI  - Determination of choline in milk, milk powder, and soy lecithin hydrolysates by
      flow injection analysis and amperometric detection with a choline oxidase based
      biosensor.
AB  - A fast-response and interference-free amperometric biosensor based on choline
      oxidase immobilized onto an electropolymerized polypyrrole film for flow
      injection determination of choline in milk, milk powder, and soy lecithin
      hydrolysates is described. The sensor displayed an Imax value of 1.9 +/- 0.2
      microA and an apparent Michaelis-Menten constant, k'M, equal to 1.75 +/- 0.07 mM.
      Detection limits of 0.12 microM could be obtained. Because even a slight
      deterioration of the anti-interference membrane can adversely affect measurement
      accuracy, a real time monitoring of the biosensor selectivity has been achieved
      by a dual Pt electrode flow-through cell where the enzyme modified electrode is
      coupled to an enzyme-free electrode in a parallel configuration. Finally,
      bracketing technique (alternate injections of sample and standards) allows a two
      point calibration to be performed in real-time, correcting for any drift in
      sensor response.

PMID- 15264894
TI  - Optimization of a liquid chromatography-tandem mass spectrometry method for
      quantification of the plant lignans secoisolariciresinol, matairesinol,
      lariciresinol, and pinoresinol in foods.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      for the quantification of the four major enterolignan precursors
      [secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol] in foods.
      The method consists of alkaline methanolic extraction, followed by enzymatic
      hydrolysis using Helix pomatia (H. pomatia) beta-glucuronidase/sulfatase. H.
      pomatia was selected from several enzymes based on its ability to hydrolyze
      isolated lignan glucosides. After ether extraction samples were analyzed and
      quantified against secoisolariciresinol-d8 and matairesinol-d6. The method was
      optimized using model products: broccoli, bread, flaxseed, and tea. The yield of
      methanolic extraction increased up to 81%, when it was combined with alkaline
      hydrolysis. Detection limits were 4-10 microg/(100 g dry weight) for solid foods
      and 0.2-0.4 microg/(100 mL) for beverages. Within- and between-run coefficients
      of variation were 6-21 and 6-33%, respectively. Recovery of lignans added to
      model products was satisfactory (73-123%), except for matairesinol added to bread
      (51-55%).

PMID- 15264895
TI  - New method for a two-step hydrolysis and chromatographic analysis of pectin
      neutral sugar chains.
AB  - A new method for the determination of the main neutral sugars in pectin has been
      developed. The sample preparation involves a mild chemical attack followed by an
      enzymatic hydrolysis. The completeness and nondestructive character of the method
      are demonstrated by comparison of the results obtained with different acids such
      as H2SO4, HCl, and trifluoroacetic acid (TFA) at different concentrations (2, 1,
      or 0.2 M) at two temperatures (80 or 100 degrees C). The chemical hydrolysis of
      pectin neutral sugar chains with strong acid (1 or 2 M) and high temperature (100
      degrees C) shows that the liberation of the pectin sugars is not realized at the
      same rate for each sugar. Different optimum conditions are thus obtained.
      However, the chemical pectin hydrolysis with 0.2 M TFA at 80 degrees C is
      characterized by the liberation of pectin neutral sugar side chains without any
      degradation within 72 h of hydrolysis. Under these conditions, the liberation of
      some pectin sugars, essentially galactose, glucose, and rhamnose, was not
      complete. An enzymatic hydrolysis is necessary to obtain a complete release of
      all the sugars. The combination of the two treatments, a chemical hydrolysis
      realized with diluted acid (0.2 M) for 72 h at low temperature (80 degrees C) on
      one hand and an enzymatic hydrolysis on the other hand, allow a total liberation
      of pectin sugars. The quantitative analysis of the carbohydrates is realized with
      accuracy, high selectivity, and sensitivity with high-performance anion-exchange
      chromatography with pulsed-amperometric detection. The sugars can be analyzed
      without any derivatization with a limit of quantification of 0.1 mM.

PMID- 15264896
TI  - Inhibitory Effects of the C-2 Epimeric Isomers of Tea Catechins on Mouse Type IV
      Allergy.
AB  - The inhibitory effects of C-2 epimeric isomers of (-)-epigallocatechin-3-O
      gallate (EGCG) and two O-methylated EGCG derivatives, (-)-epigallocatechin-3-O-(3
      O-methyl)gallate (EGCG3''Me) and (-)-epigallocatechin-3-O-(4-O-methyl)gallate
      (EGCG4''Me), against oxazolone-induced type IV allergy in male mice were
      investigated. These compounds exhibited strong antiallergic effects by
      percutaneous administration at a dose of 0.13 mg/ear. The inhibition rates of (-)
      gallocatechin-3-O-gallate (GCG), (-)-gallocatechin-3-O-(3-O-methyl)gallate
      (GCG3''Me), and (-)-gallocatechin-3-O-(4-O-methyl)gallate (GCG4''Me) on mouse
      type IV allergy were 52.1, 53.3, and 54.8%, respectively. However, the
      antiallergic effects were weaker than those of their corresponding original tea
      catechins (2R,3R type). The inhibition rates of those were 88.0, 73.2, and 77.6%,
      respectively. For all of the catechins tested, oral administration at a dose of
      50 mg/kg body weight significantly suppressed the allergic symptoms. The
      inhibitory rates varied from 24.0 to 60.6%. No significant differences were
      observed between the effects of the epimers (2S,3R type) and their corresponding
      original catechins (2R,3R type). The antiallergic effects of tea catechins and
      their C-2 epimers observed in this study were dose-dependent. These results
      suggest that C-2 epimers of tea catechins, which are produced during heat
      processing at high temperatures, could be disadvantageous for the antiallergic
      effects on type IV allergy.

PMID- 15264897
TI  - Novel flavonol glycoside, 7-O-methyl mearnsitrin, from Sageretia theezans and its
      antioxidant effect.
AB  - A novel flavonol glycoside, 7-O-methylmearnsitrin (7,4'-O-dimethylmyricetin 3-O
      alpha-L-rhamnopyranoside), and myricetrin, kaempferol 3-O-alpha-L
      rhamnopyranoside, europetin 3-O-alpha-L-rhamnoside, and 7-O-methyl quercetin 3-O
      alpha-L-rhamnopyranoside were isolated from the leaves of Sageretia theezans, and
      their chemical structures were identified by spectroscopic analyses including two
      dimensional NMR (HSQC, HMBC). Whereas myricetrin, europetin 3-O-alpha-L
      rhamnoside, and 7-O-methylquercetin 3-O-alpha-L-rhamnopyranoside showed stronger
      activities than ascorbic acid and alpha-tocopherol, 7-O-methylmearnsitrin showed
      very weak antioxidant activities by ESR and LDL oxidation inhibition tests.

PMID- 15264898
TI  - Estimation of scavenging activity of phenolic compounds using the ABTS(*+) assay.
AB  - Observations on the applicability of the ABTS(*+) assay to define structure
      activity relationships (SARs) among phenols (AH) were based on experimental data
      and theoretical calculations. All AH examined (hydroxycinnamic derivatives,
      simple polyphenols, polyhydroxybenzoates, and flavonoids) were found to be active
      toward ABTS(*+). Moreover, known weak radical scavengers (i.e., coumaric and
      isoferulic acids) were found to be efficient or comparatively active to caffeic
      or rosmarinic acids in contradiction to the AH classification based on 1,1
      diphenyl-2-picrylhydrazyl (DPPH) data or the bond dissociation enthalpy values.
      This behavior was observed both in ethanol and in buffered (pH 7.4) environment.
      Resorcinol and phloroglucin were found to be more active than catechol and
      hydroquinone, whereas, among polyhydroxybenzoates, 2,4-dihydroxybenzoic acid was
      the least active, in line with the DPPH and theoretical data. Therefore, it can
      be argued that the ABTS(*+) assay may give an indication for the presence of
      antioxidants in a certain system but SARs cannot be readily inferred.

PMID- 15264900
TI  - Radical scavenging activities of peels and pulps from cv. Golden Delicious apples
      as related to their phenolic composition.
AB  - The relationship between phenolic composition and radical scavenging activity of
      apple peel and pulp was investigated in fruit produced according to both organic
      and integrated agricultural methods. Apple tissue extracts were subjected to high
      performance liquid chromatography separation, which showed that as compared with
      pulps, peels are richer in almost all of the quantified phenolics. Flavonols,
      flavanols, procyanidins, dihydrochalcones, and hydroxycinnamates were the
      identified phenolic classes in peel tissue, and the most abundant compounds were
      epicatechin, procyanidin B2, and phloridzin. Pulps were poorer in phytochemicals.
      Their major phenolics were procyanidins and hydroxycinnamates. Flavonols in
      amounts <20 mg kg(-1) fresh weight (fw) were also found. In both peels and pulps,
      integrated production samples were richer in polyphenols. Among the 14 compounds
      identified, only phloridzin had a tendency to appear higher in organic peels. The
      total antioxidant capacities (TAC) of extracts were evaluated using the 1,1
      diphenyl-2-picrylhydrazyl radical assay and were expressed as Trolox equivalents.
      Integrated peels gave the highest TAC (18.56 mM kg(-1) fw), followed by organic
      peels (TAC = 14.96), integrated pulps (TAC = 7.12), and organic pulps (TAC =
      6.28). In peels, the top contributors to the antioxidant activity were found to
      be flavonols, flavanols, and procyanidins, which accounted for about 90% of the
      total calculated activity whereas in pulps, the TAC was primarily derived from
      flavanols (monomers and polymers) together with hydroxycinnamates. A good
      correlation between the sum of polyphenols and the radical scavenging activities
      was found. Among the single classes of compounds, procyanidins (in peels and
      pulps) and flavonols (in peels) were statistically correlated to the TAC.

PMID- 15264899
TI  - Preparation and promotion of fruit growth in kiwifruit of fluorinated N-phenyl-N'
      1,2,3-thiadiazol-5-yl ureas.
AB  - Seventeen phenyl-fluorinated analogues of thidiazuron [N-phenyl-N'-(1,2,3
      thiadiazol-5-yl)urea, TDZ] have been prepared and characterized. The effects of
      each fluorinated urea on growth and quality of kiwifruits (Actinidia deliciosa)
      were evaluated by comparison with untreated (control) and TDZ-treated fruits. The
      results obtained showed a clear dependence of the growth-promoting activity of
      these fluorinated ureas on the pattern and degree of fluorine substitution in the
      phenyl ring. The most effective for promoting fruit growth was N-(2,3,5,6
      tetrafluorophenyl)-N'-(1',2',3'-thiadiazol-5'-yl)urea at 25 ppm (at harvest,
      treated fruits were 58% heavier than untreated ones) followed by N-(3,5
      difluorophenyl)-N'-(1',2',3'-thiadiazol-5'-yl)urea at 10 ppm (50%).
      Comparatively, TDZ-treated fruits were 31% (10 ppm) and 38% (25 ppm) heavier than
      untreated ones. The results also indicate that the effects of the more active
      phenyl-fluorinated ureas on some standard quality parameters of fruits, for
      example, percent of fruit dry matter content, soluble solids contents, total
      titratable acids, shape, and internal structure, are similar to those of TDZ.
      Quantitative structure-activity relationships have been derived for the fruit
      growth promoting activity of the phenyl-fluorinated analogues of TDZ.

PMID- 15264901
TI  - Evaluation of antioxidant capacity of cereal brans.
AB  - Several oat brans (crunchy oat bran, oat bran alone, and oat breakfast cereal)
      and wheat brans (wheat bran alone, wheat bran powder, wheat bran with malt
      flavor, bran breakfast cereal, tablet of bran, and tablet of bran with cellulose)
      used as dietary fiber supplements by consumers were evaluated as alternative
      antioxidant sources (i) in the normal human consumer, preventing disease and
      promoting health, and (ii) in food processing, preserving oxidative alterations.
      Products containing wheat bran exhibited higher peroxyl radical scavenging
      effectiveness than those with oat bran. Wheat bran powder was the best hydroxyl
      radical (OH*) scavenger. In terms of hydrogen peroxide (H2O2) scavenging, wheat
      bran alone was the most effective, while crunchy oat bran, oat bran alone, and
      oat breakfast cereal did not scavenge H2O2. The shelf life of fats (obtained by
      the Rancimat method for butter) increased most in the presence of crunchy oat
      bran. When the antioxidant activity during 28 days of storage was measured by the
      linoleic acid assay, all of the oat and wheat bran samples analyzed showed very
      good antioxidant activities. The Trolox equivalent antioxidant capacity (TEAC)
      assay was used to provide a ranking order of antioxidant activity. The wheat bran
      results for TEAC (6 min), in decreasing order, were wheat bran powder > wheat
      bran with malt flavor > or = wheat bran alone > or = bran breakfast cereal >
      tablet of bran > tablet of bran with cellulose. The products made with oat bran
      showed lower TEAC values. In general, avenanthramide showed a higher antioxidant
      level than each of the following typical cereal components: ferulic acid,
      gentisic acid, p-hydroxybenzoic acid, protocatechuic acid, syringic acid,
      vanillic acid, vanillin, and phytic acid.

PMID- 15264902
TI  - Fungistatic and bacteriostatic activities of alkamides from Heliopsis longipes
      roots: affinin and reduced amides.
AB  - This work demonstrates the fungistatic and bacteriostatic activities of affinin,
      the main alkamide of Heliopsis longipes (Gray) Blake (Asteraceae) roots and two
      alkamides obtained by catalytic reduction of affinin: N-isobutyl-2E-decenamide
      and N-isobutyl-decanamide. The bioactivity was tested against Rhizoctonia solani
      groups AG3 and AG5, Sclerotium rolfsii, Sclerotium cepivorum, Fusarium sp.,
      Vertcillium sp., phytopathogenic fungi; Phytophthora infestans, a phytopathogenic
      Chromista; Saccharomyces cerevisiae, a nonphytopathogenic ascomycete; and
      Escherichia coli, Erwinia carotovora, and Bacillus subtilis, bacteria. Affinin,
      being the primary component of the lipidic fraction, is expected to be
      responsible for the fungitoxic activity observed in roots of this plant species.
      Four of the assayed fungi showed an important sensitivity to the presence of
      affinin: S. rolfsii, S. cepivorum, P. infestans, and R. solani AG-3 and AG-5,
      displaying a growth inhibition of 100%. S. cerevisiaeshowed a similar growth
      inhibition with affinin. None of the alkamides obtained by catalytic reduction of
      affinin showed a fungitoxic activity. Affinin had a definite negative effect on
      the growth of E. coli and B. subtilis, but E. carotovora carotovora was not
      sensitive to the highest dose of affinin assayed. N-Isobutyl-2E-decenamide
      displayed a higher bacteriostatic activity against E. coli and E. carotovora
      carotovora. In both cases, this alkamide was more potent than affinin. On the
      other hand, only N-isobutyl-decanamide displayed a significant activity on the
      growth of B. subtilis.

PMID- 15264903
TI  - Quince (Cydonia oblonga Miller) fruit (pulp, peel, and seed) and Jam: antioxidant
      activity.
AB  - To study the antioxidant activity of quince fruit (pulp, peel, and seed) and jam,
      methanolic extracts were prepared. Each extract was fractionated into a phenolic
      fraction and an organic acid fraction and was analyzed by high-performance liquid
      chromatography (HPLC)/diode array detection and HPLC/UV, respectively.
      Antiradical activities of the extracts and fractions were evaluated by a
      microassay using 1,1'-diphenyl-2-picrylhydrazyl. The phenolic fraction always
      exhibited a stronger antioxidant activity than the whole methanolic extract.
      Organic acid extracts were always the weakest in terms of antiradical activity,
      which seems to indicate that the phenolic fraction gives a higher contribution
      for the antioxidant potential of quince fruit and jam. The evaluation of the
      antioxidant activity of methanolic extracts showed that peel extract was the one
      presenting the highest antioxidant capacity. The IC50 values of quince pulp,
      peel, and jam extracts were correlated with the caffeoylquinic acids total
      content. Among the phenolic fractions, the seed extract was the one that
      exhibited the strongest antioxidant activity. The IC50 values of quince pulp,
      peel, and jam phenolic extracts were strongly correlated with caffeoylquinic
      acids and phenolics total contents. For organic acid fractions, the peel extract
      was the one that had the strongest antiradical activity. The IC50 values of
      quince pulp, peel, and jam organic acid fractions were correlated with the
      ascorbic acid and citric acid contents.

PMID- 15264904
TI  - Resveratrol, pterostilbene, and piceatannol in vaccinium berries.
AB  - A study was conducted to determine the presence of resveratrol, pterostilbene,
      and piceatannol in Vaccinium berries. Samples representing selections and
      cultivars of 10 species from Mississippi, North Carolina, Oregon, and Canada were
      analyzed by gas chromatography/mass spectrometry. Resveratrol was found in
      Vaccinium angustifolium (lowbush blueberry), Vaccinium arboretum (sparkleberry),
      Vaccinium ashei (rabbiteye blueberry), Vaccinium corymbosum (highbush blueberry),
      Vaccinium elliottii (Elliott's blueberry), Vaccinium macrocarpon (cranberry),
      Vaccinium myrtillus (bilberry), Vaccinium stamineum (deerberry), Vaccinium vitis
      ideae var. vitis-ideae (lingonberry), and Vaccinium vitis-ideae var. minor
      (partridgeberry) at levels between 7 and 5884 ng/g dry sample. Lingonberry was
      found to have the highest content, 5884 ng/g dry sample, comparable to that found
      in grapes, 6471 ng/g dry sample. Pterostilbene was found in two cultivars of V.
      ashei and in V. stamineum at levels of 99-520 ng/g dry sample. Piceatannol was
      found in V. corymbosum and V. stamineum at levels of 138-422 ng/g dry sample.
      These naturally occurring stilbenes, known to be strong antioxidants and to have
      cancer chemopreventive activities, will add to the purported health benefits
      derived from the consumption of these small fruits.

PMID- 15264905
TI  - Active recombinant thioredoxin h protein with antioxidant activities from sweet
      potato (Ipomoea batatas [L.] Lam Tainong 57) storage roots.
AB  - Recombinant thioredoxin h (Trx2) overproduced in Escherichia coli (M15) was
      purified by Ni2+-chelated affinity chromatography. The molecular mass of Trx2 is
      approximately 1.4 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Total antioxidant status, 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      staining, reducing power method, Fe2+-chelating ability, ferric thiocyanate (FTC)
      method, and protection of calf thymus DNA against hydroxyl radical-induced damage
      were studied. The thioredoxin h protein with a concentration of 12.5 mg/mL
      exhibited the highest activity (expressed as 0.37 +/- 0.012 mM ABTS* radical
      cation being cleared) in a total antioxidant status test. In the DPPH staining
      thioredoxin h appeared as white spots when it was diluted to 50 mg/mL (a final
      amount of 15 microg). Like the total antioxidant status, the reducing power, Fe2+
      chelating ability, FTC activity, and protection against hydroxyl radical-induced
      calf thymus DNA damage were found with the thioredoxin h protein. It was
      suggested that thioredoxin h might contribute to its antioxidant activities
      against hydroxyl and peroxyl radicals.

PMID- 15264906
TI  - Antioxidant activity of protein-bound quercetin.
AB  - Bovine serum albumin (BSA) was derivatized by covalent attachment of different
      amounts of quercetin [ratios of BSA to quercetin were 20:1, 10:1, 7:1, 5:1, and
      2:1 (w/w)]. The antioxidant activity of the protein-phenol derivatives was
      investigated using a modified TEAC assay. The results show that the covalent
      attachment of quercetin to BSA decreases the total antioxidant activity in
      comparison to an equivalent amount of free quercetin depending on the degree of
      derivatization. The derivative with the highest amount of covalently bound
      quercetin (the 2:1 derivative) showed an antioxidant activity of only 79%
      compared to an equivalent amount of free quercetin. After the enzymatic
      proteolysis of the BSA-quercetin derivatives with trypsin, the total antioxidant
      activity of the degradation products increases in comparison to the respective
      undigested derivatives but does not reach the activity of an equivalent amount of
      free quercetin. Even after 240 min of tryptic degradation, there is still a lack
      in antioxidant activity (for the 7:1 derivative nearly 33%) as compared to free
      quercetin.

PMID- 15264907
TI  - In vitro inhibition of the activation of Pro-matrix Metalloproteinase 1 (Pro-MMP
      1) and Pro-matrix metalloproteinase 9 (Pro-MMP-9) by rice and soybean Bowman-Birk
      inhibitors.
AB  - The in vitro inhibitory activity of the rice Bowman-Birk inhibitor (rBBI) or
      soybean Bowman-Birk inhibitor (sBBI) against trypsin-catalyzed activation of pro
      matrix metalloproteinase 1 or 9 (pro-MMP-1 or pro-MMP-9), respectively, was
      investigated using electrophoresis with silver staining, heparin-enhanced
      zymography, biotinylated gelatin, Biotrak assay, and fluorescence quenched
      substrate hydrolysis. rBBI at concentrations of 0.08-0.352 mg/mL dose-dependently
      inhibited the in vitro activation of 45 microg/mL pro-MMP-1 by trypsin. Heparin
      enhanced zymography analysis of pro-MMP-1, trypsin-activated MMP-1, and a mixture
      of pro-MMP-1-trypsin-rBBI showed clear zones associated with trypsin-activated
      MMP-1 and the absence of clear zones in lanes containing pro-MMP-1 or a mixture
      of pro-MMP-1, trypsin, and rBBI. The results of the Biotrak assay also indicated
      that rBBI dose-dependently suppressed the activation of pro-MMP-1 by trypsin.
      sBBI dose-dependently inhibited the activation of 100 microg/mL of pro-MMP-9 by
      trypsin. Biotinylated gelatin assays demonstrated that pro-MMP-9 or pro-MMP-9 in
      the presence of trypsin and BBI did not hydrolyze gelatin, whereas p
      aminophenylmercury acetate (APMA)-activated MMP-9 and trypsin-activated MMP-9
      caused significant hydrolysis of gelatin. Quenched fluorescence substrate
      hydrolysis for total MMP activity showed that pro-MMP-1 or pro-MMP-9 did not
      hydrolyze the substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2; active MMP-1 or MMP
      9 hydrolyzed the substrate, but lower substrate hydrolysis was obtained when pro
      MMP-1 or pro-MMP-9 was incubated with trypsin in the presence of increasing
      concentrations of rBBI. The results are discussed in light of the role of MMP-1
      and MMP-9 in the process of angiogenesis and the potential of rBBI or sBBI as a
      functional food ingredient.

PMID- 15264908
TI  - Evaluation of calcium-alginate gel as an artificial diet medium for bioassays on
      common cutworms.
AB  - A calcium-alginate gel diet was developed for Spodoptera litura larvae, and its
      reliability as a carrier for incorporating antifeedants as well as insecticides
      was investigated. The alginate gel diet was prepared with a simple protocol,
      which does not involve any heating process. When tested using this diet,
      acephate, a Bacillus thuringiensis endotoxin formulation and rotenone
      reproducibly showed insecticidal activity against the larvae, while neem oil and
      scabequinone deterred the larval feeding effectively. However, not only the
      insecticidal activity of acephate but also the antifeedant activity of neem oil
      was reduced by replacing the alginate component by agar in the diet, suggesting
      the usefulness of the alginate gel diet as an assay tool for testing a broad
      range of samples against the larvae.

PMID- 15264909
TI  - Ferulic acid crosslinks in asparagus cell walls in relation to texture.
AB  - Post-harvest toughening of asparagus spears is associated with a large increase
      in monomeric and diferulic acids in the cell walls of stem tissues. The purpose
      of this study has been to investigate the distribution of these phenolic
      components among cell wall polymers and the role they play in the formation of
      associated pectic-xylan-phenolic complexes in relation to post-harvest
      toughening. The phenolic esters are found in all the extractable polysaccharide
      fractions, particularly the 0.5 M KOH fraction, as well as the insoluble
      cellulose-rich residue. The storage-related increase occurs in all fractions but
      is most prominent in the 0.5 M KOH-soluble components. Degradation of 0.5 M KOH
      subfractions with pure polysaccharide degrading enzymes has confirmed the
      occurrence of pectic-xylan-phenolic complexes in which ferulic acid and its
      dehydrodimers are attached to the xylan component but not to the pectic
      component. Studies on cell separation show that the maturation- and storage
      related increase in thermal stability of cell adhesion (and therefore texture) is
      probably due to an increase in phenolic cross linking of xylans mainly in the
      parenchyma tissues. This overcomes the thermal lability of the pectic
      polysaccharides that are responsible for cell adhesion in immature tissues. The
      storage-induced appearance of some of the diferulic acid moieties in a number of
      wall polymer fractions supports the hypothesis that the storage affect is a wound
      induced response rather than a continuation of maturation-related activity.

PMID- 15264910
TI  - Quantitation of 3-aminopropionamide in potatoes-a minor but potent precursor in
      acrylamide formation.
AB  - 3-Aminopropionamide (3-APA) has recently been suggested as a transient
      intermediate in acrylamide (AA) formation during thermal degradation of
      asparagine initiated by reducing carbohydrates or aldehydes, respectively. 3-APA
      may also be formed in foods by an enzymatic decarboxylation of asparagine. Using
      a newly developed method to quantify 3-APA based on liquid chromatography/tandem
      mass spectrometry, it could be shown that the biogenic amine was present in
      several potato cultivars in different amounts. Further experiments indicated that
      3-APA is formed during storage of intact potatoes (20 or 35 degrees C) or after
      crushing of the cells. The heating of 3-APA under aqueous or low water conditions
      at temperatures between 100 and 180 degrees C in model systems always generated
      more AA than in the same reaction of asparagine, thereby pointing to 3-APA as a
      very effective precursor of AA. While the highest yields measured were about 28
      mol % in the presence of carbohydrates (170 degrees C; aqueous buffer), in the
      absence of carbohydrates, 3-APA was even converted by about 63 mol % into AA upon
      heating at 170 degrees C under aqueous conditions. Propanoic acid amides bearing
      an amino or hydroxy group in the alpha-position, such as 2-hydroxypropionamide
      and l-alaninamide, were ineffective in AA generation indicating that elimination
      occurs only from the beta-position.

PMID- 15264911
TI  - Malate metabolism and adaptation to chilling temperature storage by pretreatment
      with high CO2 levels in Annona cherimola fruit.
AB  - In this study we focused on the effect of a pretreatment with high (20%) CO2
      levels on malic acid metabolism in cherimoya (Annona cherimola Mill) fruit stored
      at chilling temperature. We analyzed the activity of phosphoenolpyruvate
      carboxylase (PEPC), malate dehydrogenase (MDH), and the NADP-malic enzyme (NADP
      ME), involved in the carboxylation/decarboxylation of malate. Our results show
      that CO2 treatment, which improves tolerance to prolonged storage at chilling
      temperature, was closely linked to considerably greater NADP-ME activity. These
      results, combined with lower PEPC activity, may explain the significantly lower
      amount of malic acid and titratable acidity quantified in CO2-treated fruit.
      Moreover, the high cytoplasmic MDH enzyme activity and the strong stimulation of
      NADP-ME activity exhibited by CO2-treated fruit could be contributing factors in
      the maintenance of fruit energy metabolism, pH stability, and the promotion of
      synthesis of defense compounds that prevent or repair damage caused by chilling
      temperature.

PMID- 15264912
TI  - Chemical characterization of lignin and lipid fractions in kenaf bast fibers used
      for manufacturing high-quality papers.
AB  - The chemical composition of lignin and lipids of bast fibers from kenaf (Hibiscus
      cannabinus) used for high-quality paper pulp production was studied. Pyrolysis
      gas chromatography/mass spectrometry (Py-GC/MS) of fibers showed a lignin with a
      high syringyl/guaiacyl ratio (5.4) and minor amounts of p-hydroxyphenyl units.
      Simultaneously, sinapyl and coniferyl acetates were also identified, indicating
      that this lignin is partially acetylated. p-Hydroxycinnamic acids were found in
      only trace amounts. The main lipids identified by GC/MS of extracts from kenaf
      fibers were series of long-chain n-fatty acids, waxes, n-alkanes, and n-fatty
      alcohols. Free and esterified sterols and triterpenols, steroid hydrocarbons, and
      steroid and triterpenoid ketones, as well as steryl glycosides, were also found.
      Finally, the fate of the main constituents of kenaf fibers in alkaline pulping
      was also investigated.

PMID- 15264913
TI  - Countercurrent supercritical fluid extraction and fractionation of high-added
      value compounds from a hexane extract of olive leaves.
AB  - Countercurrent supercritical fluid extraction (CC-SFE) at a pilot scale plant was
      used for fractionation of high-added-value products from a raw extract of olive
      leaves in hexane. Compounds found in the raw extract were waxes, hydrocarbons,
      squalene, beta-carotene, triglycerides, alpha-tocopherol, beta-sitosterol, and
      alcohols. The CC-SFE extraction process was investigated according to a 2(3) full
      factorial experimental design using the following variables and ranges:
      extraction pressure, 75-200 bar; extraction temperature, 35-50 degrees C; and
      ethanol as modifier, 0-10%. Data were analyzed in terms of extraction yield,
      enrichment, recovery, and selectivity. Higher extraction yields were attained at
      200 bar. For most of the compounds analyzed enrichment was attained at the same
      conditions, that is, 75 bar, 35 degrees C, and 10% ethanol. Hydrocarbons were
      usually recovered in the separators, whereas waxes and alpha-tocopherol remain in
      the raffinate. Selectivity data reveal that alpha-tocopherol is the most easily
      separable compound. The influence of the experimental factors on the recovery of
      all the compounds was studied by means of regression models. The best fitted
      model was attained for beta-sitosterol, with R2 = 99.25%.

PMID- 15264914
TI  - Effect of drying conditions and storage period on polyphenolic content,
      antioxidant capacity, and ascorbic acid of prunes.
AB  - In this study the main chemical parameters, ascorbic acid and polyphenol content,
      and antioxidant activity of two varieties of prunes, dried by high-temperature
      (85 + 70 degrees C) and low-temperature (60 degrees C) procedures, were monitored
      during storage. Ascorbic acid content was higher in the prunes dried at 60
      degrees C but significantly decreased in both varieties during storage. The
      different classes of polyphenols analyzed (cinnamates, anthocyanins, flavonols)
      showed different stabilities during storage. Neochlorogenic acid decreased only
      in the President variety, whereas chlorogenic acid increased in both varieties;
      anthocyanins, present only in the President prunes, disappeared in the first
      months of storage, and the flavonol content fell significantly in both cultivars
      during the year of the study. Drying temperature significantly affected the
      polyphenol content, with different effects according to the class of polyphenols.
      Antioxidant activity showed a significant increase at the end of the storage
      period and in the President variety was higher in the sample dried at the higher
      temperature.

PMID- 15264915
TI  - Enhancement of tofu isoflavone recovery by pretreatment of soy milk with koji
      enzyme extract.
AB  - Isoflavones are novel nutraceutical constituents of soybeans, but considerable
      amounts are lost in the whey during conventional tofu manufacturing. In this
      study, in a small-scale process, 2 mL of koji enzyme extract (soybean
      koji/deionized water, 1/3, w/v) was combined with 600 mL of soy milk, and 30 mL
      aliquots were incubated at 35 degrees C for 0, 30, 60, 120, and 300 min, for
      enzyme pretreatment. After each treatment time, soy milk was heated to 85 degrees
      C, CaSO4 was added to aggregate protein, and the mixture was centrifuged to
      separate the solids (tofu) from the whey. The tofu yield and moisture contents
      from soy milk treated for 30 or 60 min were higher than those from soy milk
      treated for 0 (control), 120, or 300 min. The protein content of freeze-dried
      tofu varied in a limited range, and native PAGE and SDS-PAGE patterns revealed
      slight quantitative and qualitative variations among products. Soy milk daidzein
      and genistein contents increased while daidzin and genistin contents decreased as
      the time of enzyme pretreatment of the soy milk increased. After 30 min of
      pretreatment, daidzin, genistin, daidzein, and genistein contents recovered in
      tofu products were higher than those of the control. In a pilot-scale process,
      aliquots (3 L) of soy milk were enzyme-treated for 30 min, aggregated with CaSO4,
      and hydraulically pressed to remove the whey. As in pretreatments, soy milk
      daidzein and genistein contents increased while daidzin and genistin contents
      decreased. In a comparison of the control and enzyme-treated tofu products, the
      total recoveries of daidzin, genistin, daidzein, and genistein in the tofu
      products increased from 54.9% to 64.2%. When the tofu products were subjected to
      a sensory panel test, both products were judged acceptable.

PMID- 15264916
TI  - Lipid composition of lees from Sherry wine.
AB  - In this paper, we describe the study and characterization of the lipids from lees
      of Sherry wine, one of the main byproducts from the wine-making industry in the
      Jerez/Xeres/Sherry denomination of the origin zone in Jerez de la Frontera,
      Spain. The lipid content, extractability, classification, fatty acid composition,
      and its main chemical characteristics have been determined in order to evaluate
      their potential use as a food or food additive.

PMID- 15264917
TI  - Characterization of carrot root oil arising from supercritical fluid carbon
      dioxide extraction.
AB  - Carrot root oil (SCO), obtained by supercritical fluid carbon dioxide (SC-CO2)
      extraction, was characterized and compared to a commercial carrot oil (MCO) and a
      virgin olive oil (VOO) (cv. Coratina). SCO showed much higher contents of
      carotenes, phenolics, waxes, phytosterols, and sesquiterpene and monoterpene
      volatiles. In SCO, the most prominent components present in the fully
      investigated analytical fractions (fatty acids, triglycerides, waxes,
      phytosterols, long-chain aliphatic alcohols, superior triterpene alcohols, and
      volatiles) were, respectively, linolenic acid, trilinolein, waxes C38, beta
      sitosterol, campesterol and stigmasterol, 1-hexacosanol, 24-methylencycloartanol
      and cycloartenol, beta-caryophyllene, alpha-humulene, alpha-pinene, and sabinene.
      In VOO, the major constituents of the above analytical classes were,
      respectively, oleic acid, trilinolein, waxes C36, unsaturated volatile C6
      aldehydes (trans-2-hexenal most markedly), and the same prominent sterols and
      superior alcohols found in SCO. In MCO, which also contained a proportion of
      unknown plant oil, several components showed magnitudes that were lower compared
      to SCO but higher with respect to VOO. The last had the aliphatic and triterpene
      alcohol concentration higher compared to that of both SCO and MCO. Several
      chemometric methods, applied to different analytical data sets, proved to be
      effective in grouping the three oil kinds.

PMID- 15264918
TI  - Spelt (Triticum spelta L.) and winter wheat (Triticum aestivum L.) wholemeals
      have similar sterol profiles, as determined by quantitative liquid chromatography
      and mass spectrometry analysis.
AB  - From a nutritional point of view, cereal lipids include valuable molecules, such
      as essential fatty acids, phytosterols, and fat-soluble vitamins. Spelt (Triticum
      spelta L.) is an alternative hulled bread cereal mostly grown in Belgium, where
      it is mainly intended for animal feed but should increasingly be used for human
      consumption. The present research focused on phytosterol quantification by
      LC/APCI-MS2 in saponified wholemeal extracts of 16 dehulled spelt and 5 winter
      wheat (Triticum aestivum L.) varieties grown in Belgium during 2001-2002 at the
      same location. Glycosylated sterols and free and formerly esterified sterols
      could be determined in saponified extracts. Results show that the mean
      phytosterol content is comparable in both cereals (whereas other lipids, such as
      oleic and linoleic acids, are increased in spelt wholemeal): spelt extract has,
      on average, 527.7 microg of free and esterified sterols g(-1) of wholemeal and
      123.8 microg of glycosylated sterols g(-1) of wholemeal versus 528.5 and 112.6
      microg x g(-1) in winter wheat (values not corrected for recoveries). This is the
      first report on the application and validation of an LC/MS2 method for the
      quantification of phytosterols in spelt and winter wheat.

PMID- 15264919
TI  - Analysis of phenolic compounds in white rice, brown rice, and germinated brown
      rice.
AB  - Two hydroxycinnamate sucrose esters, 6'-O-(E)-feruloylsucrose and 6'-O-(E)
      sinapoylsucrose, were isolated from methanol extracts of rice bran. Soluble and
      insoluble phenolic compounds as well as 6'-O-(E)-feruloylsucrose and 6'-O-(E)
      sinapoylsucrose from white rice, brown rice, and germinated brown rice were
      analyzed using HPLC. The results demonstrated that the content of insoluble
      phenolic compounds was significantly higher than that of soluble phenolics in
      rice, whereas almost all compounds identified in germinated brown rice and brown
      rice were more abundant than those in white rice. 6'-O-(E)-Feruloylsucrose (1.09
      mg/100 g of flour) and 6'-O-(E)-sinapoylsucrose (0.41 mg/100 g of flour) were
      found to be the major soluble phenolic compounds in brown rice. During
      germination, an approximately 70% decrease was observed in the content of the two
      hydroxycinnamate sucrose esters, whereas free phenolic acid content increased
      significantly; the ferulic acid content of brown rice (0.32 mg/100 g of flour)
      increased to 0.48 mg/100 g of flour and became the most abundant phenolic
      compound in germinated brown rice. The content of sinapinic acid increased to
      0.21 mg/100 g of flour, which is nearly 10 times as much as that in brown rice
      (0.02 mg/100 g of flour). In addition, the total content of insoluble phenolic
      compounds increased from 18.47 mg/100 g of flour in brown rice to 24.78 mg/100 g
      of flour in germinated brown rice. These data suggest that appropriate
      germination of brown rice may be a method to improve health-related benefits.

PMID- 15264920
TI  - Controlled release of tebuconazole from a polymer matrix microparticle: release
      kinetics and length of efficacy.
AB  - Preparation and characterization of microencapsulated tebuconazole, its release
      kinetics in water, and the bioefficacy of these formulations in controlling wheat
      rust in spring wheat is described herein. Controlled-release (CR) formulations
      based on matrix microparticles were prepared by the oil-in-water emulsion
      process. Polymer-based matrix was prepared from poly(methyl methacrylate) (PMMA)
      and poly(styrene-co-maleic anhydride) (PSMA). Modification of the matrix was
      achieved by the use of different low molecular weight or polymeric additives.
      These additives were found to lower the glass transition temperature of the
      matrix and enhance the release rate of tebuconazole in water, under infinite sink
      conditions. Release of tebuconazole from matrix microparticles was found to be
      diffusion controlled. CR formulations were found to be very efficacious in
      controlling wheat rust. Soil-applied CR formulations prepared from a PMMA or PSMA
      matrix, modified with poly(vinyl acetate), were as effective in controlling wheat
      rust (Puccinia recondita) as foliar-applied tebuconazole, Raxil, from Bayer AG.
      Results suggest that CR formulations with a systemic fungicide, such as
      tebuconazole, applied as either a soil or seed treatment, may provide control of
      foliar diseases, possibly eliminating or reducing the need for traditional foliar
      applications.

PMID- 15264921
TI  - Stir bar sorptive extraction applied to volatile constituents evolution during
      Vitis vinifera ripening.
AB  - The stir bar sorptive extraction (SBSE) technique is used to determine volatile
      constituents in Monastrell grapes. The method proposed involves a maceration step
      lasting 2 h and a sorption time of 6 h. The coefficients of variation obtained
      were <4% in the case of the volatile compounds and <2% for the internal standard.
      The behavior of the volatiles during grape ripening was studied, and 34 compounds
      were determined, among which geranyl acetone, geranyl butyrate, farnesol, and a
      bicycloterpene, tentatively identified as 6-methylene[3.1.0]byciclohexane, were
      recorded for the first time in this variety. The highest terpene and
      norisoprenoid contents together with the lowest values of C6 compounds were
      observed during the fifth week of ripening, meaning that this would be the
      optimal time for harvesting in terms of volatile compounds.

PMID- 15264922
TI  - Identification of fruity/fermented odorants in high-temperature-cured roasted
      peanuts.
AB  - Gas chromatography/olfactometry on a concentrate of volatiles obtained by solvent
      assisted flavor evaporation (SAFE) from roasted peanuts containing a
      fruity/fermented off-note was used to identify the odorants responsible for the
      flavor defect. Freshly dug peanuts were divided into two classes, mature and
      immature, using pod mesocarp color, and subjected to normal (27 degrees C) and
      high (40 degrees C) temperature curing. Sensory evaluation of the roasted peanuts
      found that immature peanuts cured at high temperature contained the
      fruity/fermented off-note. Mature peanuts cured at high temperature and both
      immature and mature peanuts cured at low temperature were free of the off-note.
      Peanuts with the off-flavor were found to contain fruit-like esters (ethyl 2
      methylpropanoate, ethyl 2-methylbutanoate, and ethyl 3-methylbutanoate) along
      with increased levels of short chain organic acids (butanoic, 3-methylbutanoic,
      and hexanoic). These findings were confirmed by sensory evaluation of models,
      where the addition of these compounds produced the fruity/fermented flavor defect
      in a control peanut paste. This is the first time that the odorants responsible
      for this off-note in roasted peanuts have been identified.

PMID- 15264923
TI  - Controlled continuous flow delivery system for investigating taste-aroma
      interactions.
AB  - A multichannel flavor delivery system, Dynataste, was developed. Controlled
      amounts of isoamyl acetate (100 ppm) and sucrose (0-3%) solution was administered
      to experienced and naive assessors who used time intensity techniques to record
      perceived 'fruit' flavor intensity. In-nose volatile delivery was monitored using
      atmospheric pressure chemical ionization-mass spectrometry. Results indicated
      that sucrose is a key driver of fruit flavor intensity but that the magnitude of
      the effect varies between individuals. The combined temporal analysis of chemical
      stimuli in vivo and sensory data indicate evidence of interactions at a
      perceptual level. Comparison of experienced and naive assessors revealed cross
      modal interactions in each group, although a subgroup of experienced assessors
      was unaffected by changes in sucrose concentration. This raises the question of
      the selected use of experienced panels in cross modal investigations.

PMID- 15264924
TI  - Impact of blanching and packaging atmosphere on the formation of aroma compounds
      during long-term frozen storage of leek (Allium ampeloprasum Var. Bulga) slices.
AB  - The content of aroma compounds and the catalytic activity of lipoxygenase (LOX),
      alliinase, hydroperoxide lyase (HPL), and alcohol dehydrogenase (ADH) were
      analyzed in unblanched and blanched 15-mm leek slices packed in atmospheric air
      (21% O2) or 100% nitrogen (0% O2) three times during 12 months of frozen storage
      (12 M). The total amount of sulfur compounds and the total amount of aldehydes
      were greatly influenced by storage time, atmosphere, and blanching [concentration
      of sulfur compounds in fresh unblanched (UNB) slices = 1.35 mg/L, fresh blanched
      (B) slices = 1.09 mg/L, UNB 21% O2 12 M = 0.656 mg/L, UNB 0% O2 12 M = 2.11 mg/L,
      B 21% O2 12 M = 1.14 mg/L, B 0% O2 12 M = 1.59 mg/L]. B 0% O2 was closest to the
      original ratio between sulfur compounds and aldehydes after 12 months. The
      activities of HPL and alliinase were totally lost after 12 months, and ADH showed
      minimal activity, whereas LOX (UNB 0% O2) showed approximately 25% of the
      original activity. LOX was the most and HPL the least heat labile enzyme
      investigated.

PMID- 15264925
TI  - Fresh Israeli Jaffa blond (Shamouti) orange and Israeli Jaffa red Star Ruby
      (Sunrise) grapefruit juices affect plasma lipid metabolism and antioxidant
      capacity in rats fed added cholesterol.
AB  - The bioactivity of Israeli Jaffa blond (Shamouti) fresh orange and Israeli Jaffa
      red Star Ruby (Sunrise) grapefruit juices was investigated in vitro and in vivo.
      The contents of bioactive compounds of these juices were determined. The
      influence of bioactive compounds on plasma lipids and plasma antioxidant activity
      in rats fed cholesterol-containing and cholesterol-free diets was assessed.
      Significant differences in the contents of dietary fibers were not found. The
      contents of total polyphenols, flavonoids, and anthocyanins in fresh orange and
      grapefruit juices were 962.1 +/- 27.2 and 906.9 +/- 27.1; 50.1 +/- 3.3 and 44.8
      +/- 3.2; and 69.9 +/- 5.6 and 68.7 +/- 5.5 microg/mL, respectively. The
      antioxidant potential measured by the scavenging activity against nitric oxide,
      the beta-carotene-linoleate model system (beta-carotene), and the 1,1-diphenyl-2
      picrylhydrazyl and 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid)
      diamonium salt assays was higher in orange juice but not significantly. A high
      level of correlation between contents of total polyphenols and flavonoids and
      antioxidant potential values of both juices was found. Diets supplemented with
      orange and to a lesser degree with grapefruit juices improved plasma lipid
      metabolism only in rats fed added cholesterol. However, an increase in the plasma
      antioxidant activity was observed in both groups. In conclusion, fresh orange and
      grapefruit juices contain high quantities of bioactive compounds, which guarantee
      their high antioxidant potential, and the positive influence on plasma lipid
      metabolism and plasma antioxidant activity could make fresh orange and grapefruit
      juices a valuable supplement for disease-preventing diets.

PMID- 15264926
TI  - Inhibition of fish gill lipoxygenase and blood thinning effects of green tea
      extract.
AB  - The objective of the present study was to determine whether green tea extracts
      are inhibitory to lipid oxidations catalyzed by lipoxygenase (LOX) and hemoglobin
      (Hb) using fish as an animal model. Green tea was extracted with water. LOX was
      extracted from the gills of grey mullet and tilapia, respectively. The LOX
      activity was determined using chemiluminescence and high-pressure liquid
      chromatography. The green tea extract showed inhibitory effects on both LOX
      catalyzed and Hb-catalyzed oxidation of arachidonic acid and linoleic acid. Blood
      thinning effects were observed ex vivo by mixing the green tea extract with fish
      red blood cells and showed that the flow behavior of fish blood becomes closer to
      the Newtonian type with a thinner consistency. Similar effects were found on
      tilapia and grey mullet.

PMID- 15264927
TI  - Regulation of lysine metabolism and endosperm protein synthesis by the opaque-5
      and opaque-7 maize mutations.
AB  - Two high lysine maize endosperm mutations, opaque-5 (o5) and opaque-7 (o7), were
      biochemically characterized for endosperm protein synthesis and lysine metabolism
      in immature seeds. Albumins, globulins, and glutelins, which have a high content
      of lysine, were shown to be increased in the mutants, whereas zeins, which
      contain trace concentrations of lysine, were reduced in relation to the wild-type
      lines B77xB79+ and B37+. These alterations in the storage protein fraction
      distribution possibly explain the increased concentration of lysine in the two
      mutants. Using two-dimensional polyacrylamide gel electrophoresis of proteins of
      mature grains, variable amounts of zein polypeptides were detected and
      considerable differences were noted between the four lines studied. The analysis
      of the enzymes involved in lysine metabolism indicated that both mutants have
      reduced lysine catabolism when compared to their respective wild types, thus
      allowing more lysine to be available for storage protein synthesis.

PMID- 15264928
TI  - Lipid [corrected] classes, fatty acids, and sterols in seafood from Gilbert Bay,
      southern labrador.
AB  - Seafood from Gilbert Bay, southern Labrador, was sampled for lipid classes, fatty
      acid, and sterol composition. Gilbert Bay is a proposed Marine Protected Area,
      and the composition of seafood from this region is interesting from both human
      health and ecological perspectives. Analyses included four species of bivalves
      and flesh and liver samples from four fish species. Lipids from a locally
      isolated population of northern cod (Gadus morhua) were also compared to lipids
      from other cod populations. Lipid classes were analyzed by Chromarod/Iatroscan
      TLC-FID, fatty acids by GC, and sterols by GC-MS. Three cod populations had
      similar levels of total lipid per wet weight (0.6%) with triacylglycerols (TAG),
      sterols, and phospholipids comprising on average 13, 11, and 51%, respectively,
      of their total lipids. Fatty fish such as capelin and herring contained on
      average 8.4% lipid with 86% present as TAG. Fish livers from cod and herring
      showed opposite trends, with cod having elevated lipid (27%) and TAG (63%) and
      herring containing only 3.8% lipid and 20% TAG. Shellfish averaged 0.6% lipid;
      however, significant lipid class differences existed among species. Fatty acid
      analysis showed few significant differences in cod populations with on average
      57% polyunsaturated fatty acids (PUFA), 18% monounsaturated fatty acids (MUFA),
      and 24% saturated fatty acids (SFA). Cod livers had lower PUFA (34%) and elevated
      MUFA (44%) relative to flesh. Bivalves averaged 25% SFA, 18% MUFA, and 57% PUFA,
      whereas scallop adductor muscle had the highest PUFA levels (63%). Bivalves
      contained 20 different sterols with cholesterol present as the major sterol (19
      39%). trans-22-Dehydrocholesterol, brassicasterol, 24-methylenecholesterol, and
      campesterol individually accounted for >10% in at least one species. High levels
      of PUFA and non-cholesterol sterols observed in Gilbert Bay seafood demonstrate
      their positive attributes for human nutrition.

PMID- 15264929
TI  - Ability of alphas-Casein to suppress the heat aggregation of ovotransferrin.
AB  - The effects of alphas-casein on heat aggregation of ovotransferrin (OT) were
      studied by heating at 80 degrees C for 20 min in 10 mM phosphate buffer, pH 7.0.
      The heat interactions between alphas-casein and OT were followed by turbidity
      development and polyacrylamide gel electrophoresis. We found that alphas-casein
      can effectively suppress the heat-induced aggregation of heat-labile OT. The
      suppressive ability of alphas-casein was reduced by the presence of NaCl on
      heating. Dephosphorylated alphas-casein had less ability to suppress the
      aggregation of OT than native alphas-casein. Our results indicate that alphas
      casein interacts with the heat-denatured OT through its exposed hydrophobic
      surface and phosphoserine residue. Such interactions seem to be important in
      helping to suppress the aggregation of heated OT. The suppressive effects of
      alphas-casein on heat aggregation of OT would be partially ascribed to the
      formation of transparent gel from egg white by the addition of alphas-casein.

PMID- 15264930
TI  - Enzymolysis approach to compare cu availability from human milk and infant
      formulas.
AB  - The purpose of the present paper is to develop an easy and quick in vitro method
      to compare copper availability from breast milk and infant formulas. This study
      focuses on the differences caused by the use of pH 2.0 (adult gastric pH) or pH
      5.0 (newborn gastric pH) in the first stage of the enzymolysis. pH affects Cu
      solubility, a possible estimator of the availability. Selection of a digestor,
      times of enzymolysis, centrifugation parameters, and Cu determination by ETAAS
      were discussed as well. Percentage of Cu solubility was larger from breast milk
      (gastric pH 2.0, 65.3 +/- 14.0 vs 40.0 +/- 13.9%; gastric pH 5.0, 61.2 +/- 16.5
      vs 26.6 +/- 10.3%), but the soluble content was larger from infant formulas for
      both pHs (gastric pH 2.0, 245.3 +/- 82.1 vs 113.0 +/- 103.4 ng mL(-1); gastric pH
      2.0, 169.3 +/- 76.9 vs 75.3 +/- 21.9 vs ng mL(-1)).

PMID- 15264931
TI  - In vitro antioxidative effects and tyrosinase inhibitory activities of seven
      hydroxycinnamoyl derivatives in green coffee beans.
AB  - Seven kinds of hydroxycinnamic acid derivatives identified as 3-caffeoylquinic
      acid (3-CQA), 4-caffeolyquinic acid (4-CQA), 5-caffeoylquinic acid (5-CQA), 5
      feruloylquinic acid (5-FQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 3,5
      dicaffeoylquinic acid (3,5-diCQA), and 4,5-dicaffoylquinic acid (4,5-diCQA) by
      MS, 1H NMR, and HPLC analyses were isolated from low-quality (immature) and
      commercial quality green coffee beans. The quantity of chlorogenic acid isomers
      (10.4 g/100 g), especially 5-CQA, in commercial green coffee beans [West Indische
      Bereiding (West India processing beans from Sumatra Island, Indonesia, WIB)] was
      higher than that in low-quality beans [9.1 g/100 g, Eerste Kwaliteit (Export low
      quality beans from Java Island, Indonesia, EK-1, grade 4)], whereas little
      difference in diCQAs was detected between the two kinds of beans. The free
      radical scavenging activity of these isolates was evaluated in assay systems
      using DPPH free radicals and superoxide anion radicals generated by xanthine-XOD.
      The diCQAs showed strong (1.0-1.8-fold) free radical scavenging activity compared
      to commonly used antioxidants such as alpha-tocopherol and ascorbic acid. The
      potency order of superoxide anion radical scavenging activity was diCQAs >
      caffeic acid, CQAs > 5-FQA. The activities of the diCQAs were twice as effective
      as those of CQAs and 4 times as effective as that of 5-FQA. The diCQAs also
      exhibited more potent (2.0-2.2-fold) tyrosinase inhibitory activities compared to
      CQAs, arbutin, and ascorbic acid. The isolates exhibited antiproliferation
      activities in four cancer cell lines, U937, KB, MCF7, and WI38-VA. Among these,
      KB cells were most sensitive (IC50 = 0.10-0.56 mM).

PMID- 15264932
TI  - Antioxidant properties of phenolic compounds from Pelargonium reniforme.
AB  - Flavonoids and hydrolyzable tannins isolated from Pelargonium reniforme were
      evaluated for their antioxidant ability using a 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical generating system and a luminol-dependent chemiluminescence assay.
      In both assays, the polyphenols tested showed higher radical scavenging
      activities than the reference antioxidant, ascorbic acid (IC50 2.6-32.9 microM vs
      40.9 microM in the DPPH test, and 2-25 times stronger effects in the
      chemiluminescence assay). A comparison of the flavonoids and the tannins showed
      that the latter have more potential than the former. Structural requirements for
      marked antioxidant activities of hydrolyzable tannins were the presence of
      galloyl and hexahydroxydiphenoyl groups, and apparently carbonyl (ester)
      functionalities in oxidatively modified dehydrohexa-hydroxydiphenoyl moieties.
      For flavonoids, it appeared that a catechol (3',4'-dihydroxy) element in the B
      ring were important determinants and that O-glycosides were more effective than
      flavone-based C-glucosyls. Conspicuously, introduction of a galloyl group
      significantly enhanced their potentials. The demonstrated marked antioxidant
      effects of the polyphenols provide a clue for beneficial effects of P. reniforme
      in the treatment of liver disorders among several ethnic groups in areas of
      southern Africa.

PMID- 15264933
TI  - The major peanut allergen Ara h 1 and its cleaved-off N-terminal peptide;
      possible implications for peanut allergen detection.
AB  - Ara h 1 was purified from raw peanuts (Arachis hypogaea L.) in the presence or
      absence of protease inhibitors. N-Terminal amino acid sequences were determined
      after western blotting. Both purification procedures proved to be very consistent
      and resulted in identical chromatographic and electrophoretic behavior of Ara h 1
      and in the isolation of identical proteins of approximately 64 kDa with
      RS/H_PPGERTRG as the N-terminal amino acid sequence. Consequently, purified Ara h
      1 appears to be truncated at the N-terminal side. The observations strongly
      suggest that Ara h 1 occurs physiologically as a protein of which the first 84
      and 78 amino acids, respectively, are cleaved off in planta upon maturation of
      the protein. On the basis of epitope mapping, the cleaved-off N-terminal peptide
      contains three allergenic epitopes, of which two are major. These truncated
      epitopes will go undetected in assays when purified Ara h 1 from peanuts is used
      as reference material. Patients' sera, however, contain IgE-type antibodies
      against the epitopes that are contained in the cleaved-off peptide, implying that
      the peptide, or part of it, is still present in peanuts that are consumed.
      Possible consequences of this exposure to these three epitopes are discussed. On
      the basis of literature data the cleaved-off peptide is hypothesized to have
      antifungal activity.

PMID- 15264934
TI  - Further studies on the anticancer activity of citrus limonoids.
AB  - Research in this laboratory has shown that some citrus limonoids can inhibit the
      development of 7,12-dimethylbenz[a]anthracene-induced oral tumors. The data from
      these studies have suggested that certain rings in the limonoid nucleus may be
      critical to antineoplastic activity. Using the hamster cheek pouch model, three
      new limonoids (ichangensin, deoxylimonin, and obacunone) have now been tested for
      cancer chemopreventive activity. In the first experiment, it was found that the
      treatments with ichangensin had no effect on tumor number or burden. In the
      second experiment, obacunone reduced tumor number and burden by 25 and 40%,
      respectively, whereas deoxylimonin reduced tumor number and burden by 30 and 50%,
      respectively. The results with deoxylimonin were significant, p < 0.05. Overall,
      the data indicated that changes in the A ring of the limonoid nucleus can lead to
      a loss of anticancer activity, whereas changes in the D ring can be tolerated
      without any apparent loss of biological activity.

PMID- 15264935
TI  - Characterization of globulins from common vetch (Vicia sativa L.).
AB  - The proteins from Vicia sativa L. (common vetch) seeds were investigated. Protein
      comprises approximately 11.4% of the seed fresh weight, >50.8% of which is
      composed by globulins and 43.6% by albumins. The globulins may be fractionated
      into two main components, which were named alpha-vicinin (comprising 73% of the
      total globulin fraction, and hence >37% of the total seed protein) and beta
      vicinin. Two minor globulin components are also present, gamma-vicinin and delta
      vicinin. alpha-Vicinin, the legumin-like globulin, with a sedimentation
      coefficient of 10.6 S, is a nonglycosylated, disulfide-bond-containing globulin,
      composed of a group of subunits with molecular masses ranging from 50 to 78 kDa.
      Upon reduction, each of these subunits releases a heavy polypeptide chain (34-66
      kDa) and a light polypeptide chain (21-23 kDa). beta-Vicinin, the vicilin-like
      globulin, with a sedimentation coefficient of 7.7 S, is a nonglycosylated
      globulin that contains no disulfide bonds and consists of two major polypeptides
      with molecular masses of 58 and 66 kDa. gamma-Vicinin is a minor, glycosylated,
      disulfide-bond-containing globulin. In the reduced form, it comprises six
      polypeptide chains with molecular masses of 12, 19, 21, 22, 23, and 31 kDa.
      Finally, delta-vicinin is a minor, highly glycosylated globulin that exhibits
      hemagglutinating activity. It is composed of a major 47 kDa polypeptide and two
      minor (33 and 38 kDa) polypeptides. N-terminal sequencing of the delta-vicinin 47
      kDa polypeptide revealed no homology to any other known storage protein.

PMID- 15264936
TI  - Insights into the reaction mechanism of the coagulation of soy protein isolates
      induced by subtilisin carlsberg.
AB  - The reaction mechanism of the coagulation of soy protein isolates (SPIs) induced
      by subtilisin Carlsberg was investigated. Formation of the coagula was monitored
      by measuring the turbidity (OD660) of the SPI solution, which decreased at the
      initial stage (phase 1 or digestion phase) of the reaction, and then increased
      (phase 2 or coagulation phase) and finally reached the plateau level. The
      velocity of the coagulation increased with increasing enzyme concentration. The
      coagulation was inhibited dramatically by adding a serine protease inhibitor
      (phenylmethanesulfonyl fluoride, PMSF) when the turbidity reached the minimum
      value. This indicates that the SPI digests participating in the coagulation are
      produced mainly in phase 2; in other words, production of the coagulating
      fragments and their coagulation occur simultaneously in phase 2. Structural
      changes of SPI during proteolysis were measured by observing fluorescence changes
      of aromatic amino acids of SPI and an externally added hydrophobic probe. It was
      suggested that the hydrophilic surface areas of SPIs might be cleaved
      preferentially in phase 1, and that the hydrophobic inner areas might be cleaved
      in phase 2 with extensive decomposition of the 3-D structure of SPI proteins. The
      fragments formed in phase 2 are considered to coagulate through hydrophobic
      interactions.

PMID- 15264937
TI  - Structural characterization of potato protease inhibitor I (Cv. Bintje) after
      expression in Pichia pastoris.
AB  - In the present study the structural properties of potato protease inhibitor 1 (PI
      1) were studied as a function of temperature to elucidate its precipitation
      mechanism upon heating. A cDNA coding for PI-1 from cv. Bintje was cloned and
      expressed in Pichia pastoris. Using the recombinant PI-1 it was suggested that PI
      1 behaves as a hexameric protein rather than as a pentamer, as previously
      proposed in the literature. The recombinant protein seems either to have a
      predominantly unordered structure or to belong to the beta-II proteins.
      Differential scanning calorimetry analysis of PI-1 revealed that its thermal
      unfolding occurs via one endothermic transition in which the hexameric PI-1
      probably unfolds, having a dimer instead of a monomer as cooperative unit. The
      transition temperature for the recombinant PI-1 was 88 degrees C. Similar results
      were obtained for a partially purified pool of native PI-1 from cv. Bintje.

PMID- 15264938
TI  - Characterization of new bisphenol a metabolites produced by CD1 mice liver
      microsomes and S9 fractions.
AB  - Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) is a widely used industrial
      chemical resulting in occupational and consumer exposure. BPA possesses weak
      estrogenomimetic activity and can be cytotoxic, though the underlying mechanisms
      of its toxicity toward cells are not completely understood. The metabolism of BPA
      by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites
      were isolated and characterized using HPLC and mass spectrometry. Many of these
      metabolites were characterized for the first time in mammals, namely isopropyl
      hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione
      conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers.
      Most of these metabolites apparently share a common metabolic pathway, for which
      considerable evidence supports the hypothesis of the production of a reactive
      intermediate, and also helps explain BPA cytotoxicity.

PMID- 15264939
TI  - Evening continuity clinic: preserving primary care education in the face of duty
      hour limitations?
AB  - OBJECTIVE: Residency programs with postcall afternoon continuity clinics violate
      the new Accreditation Council for Graduate Medical Education (ACGME) limitations
      on resident duty hours. We evaluated housestaff experience with a pilot
      intervention that replaced postcall continuity clinics with evening continuity
      clinics. METHODS: We began this pilot program at one continuity clinic site for
      pediatric residents. Instead of postcall clinics, residents had evening
      continuity clinic added to a regular clinic day when they were neither postcall
      nor on call. At 5 and 11 months, we surveyed housestaff satisfaction and
      experience with the evening clinics, particularly in comparison to postcall
      clinics. RESULTS: Nineteen of 23 pediatric residents participated in the pilot
      program. Twenty-two and 17 residents completed the 5- and 11-month follow-up
      surveys, respectively. A significantly greater proportion of residents rated
      their overall satisfaction with evening clinic as good/outstanding (16/18, 89%)
      compared with postcall clinic (2/19, 11%) at the 5-month survey (P<.01). Resident
      preference for evening clinic over postcall clinic persisted but was not
      statistically significant at 11 months (P =.05), and overall satisfaction with
      evening clinic was unchanged from the 5- and 11-month surveys (P =.64). All areas
      of patient care, medical education, and clinic infrastructure were better or
      equal in evening clinic in comparison to postcall clinic except for continuity of
      preceptors and access to medical services. CONCLUSION: Housestaff had greater
      satisfaction and a better clinic experience with evening clinic versus postcall
      clinic. Evening continuity clinic is a viable solution to meeting the ACGME work
      hour limitations while preserving housestaff primary care education.

PMID- 15264940
TI  - Can continuity of care be improved? Results from a randomized pilot study.
AB  - CONTEXT: Although continuity of care is an important component of primary care,
      few mechanisms for improving it have been studied. OBJECTIVE: To determine if
      automated reminders to providers and patient schedulers can improve continuity of
      care in a practice. DESIGN: Prospective randomized controlled trial. SETTING AND
      POPULATION: Four hundred and nine patients in the lowest tertile of continuity of
      care in a university-affiliated clinic with a computerized information system
      were randomized to 1 of 4 groups: 1) control (no reminder), 2) provider alert, 3)
      scheduler alert, or 4) provider and scheduler alert. MAIN OUTCOME MEASURES:
      Continuity of care as measured by a previously described dispersion index that
      ranges from 0 to 1.Results.-Initial continuity of care was.134 (standard
      deviation,.07). In a linear regression model, 9 months after implementation of
      the system, both the provider-prompt group (.027 [.006,.05]) and the provider and
      scheduler group (.024 [.001,.054]) were associated with increased continuity
      compared with the control group CONCLUSIONS: Prompting providers for patients
      with poor continuity of care may improve it.

PMID- 15264941
TI  - Measuring health status and quality of life for US children: relationship to
      race, ethnicity, and income status.
AB  - OBJECTIVE: Accurately measuring the health of the increasingly diverse population
      of US children requires instruments that are comparable and valid across
      cultures, economic background, and language. This paper asks: Has the field of
      pediatric health status measures reached this level of comprehensiveness?
      METHODS: Children's health status and quality of life measures commonly used in
      the United States were reviewed to assess how they have included racial/ethnic
      minority and low-income groups. Four generic and 2 condition-specific instruments
      (asthma) were examined for total sample size, percent of sample from
      racial/ethnic and low-income groups, language availability, translation methods
      for US-Spanish, reading level, and separately reported psychometric findings and
      outcomes/scores. RESULTS: Most measures have included minority groups, usually
      African American or Hispanic children, although with little information by
      Hispanic subgroup. Children's measures have generally been tested on relatively
      small samples, without separate analyses by subgroups. When done, tests of
      reliability and validity find few differences from the general population. Some
      studies report information on health by racial or ethnic group, but the findings
      are inconclusive. Economic status is usually measured in some way, but rarely are
      psychometric findings examined separately by income. When differences in health
      outcome are reported by income, lower income children usually have poorer health.
      CONCLUSIONS: Much has been accomplished in advancing health status measures for
      children. Next-generation issues include the influence of race, ethnicity, and
      income on health and health reports.

PMID- 15264942
TI  - A block rotation in community health and child advocacy: improved competency of
      pediatric residency graduates.
AB  - CONTEXT: Despite increasing recognition of the importance of community health and
      child advocacy activities by pediatricians, residency programs have had little
      experience providing this education. There are no known reports examining the
      effects of such training on residency graduates. OBJECTIVE: To determine whether
      a program for educating residents in community health and child advocacy,
      Pediatric Links With the Community (PLC), improved attitudes and competencies of
      residency graduates. DESIGN: Survey of all graduates of the Rochester Pediatric
      Residency Program from 1991-2001. Graduates before institution of PLC (pre-PLC)
      were compared with graduates after institution of PLC (post-PLC). PARTICIPANTS: A
      total of 137 (81%) of 169 graduates participated; 78 (85%) of 92 were in the pre
      PLC group and 59 (77%) of 77 were in the post-PLC group. INTERVENTION: PLC
      provides all pediatric residents with a 2-week rotation working with multiple
      community-based organizations. OUTCOME MEASURES: Differences between pre-PLC and
      post-PLC graduates in self-reported attitudes and competencies in multiple
      community health and child advocacy activities on 4-point Likert scales. RESULTS:
      The pre-PLC and post-PLC groups' attitudes toward community health activities
      were equally positive (3.4 vs 3.5, P =.08). The post-PLC group rated its
      competency higher in 8 of 12 activities (P <.05); its overall rating of
      competency was also higher (2.8 vs 2.3, P <.001). CONCLUSIONS: Although all
      pediatricians surveyed had positive attitudes toward community health and child
      advocacy activities, those who participated in PLC had higher self-perceived
      competency in most activities. Residency training programs can increase
      graduates' competence in community health skills.

PMID- 15264943
TI  - State legislator gender and other characteristics associated with sponsorship of
      child health bills.
AB  - OBJECTIVE: To examine the characteristics of state legislators who introduce
      child health bills. METHODS: We conducted a cross-sectional analysis of all bills
      introduced in Colorado, Louisiana, and Michigan during the 1997-1998 legislative
      session. We identified the topic for each bill while blinded to legislator
      characteristics. The primary study outcome was whether the bill topic related to
      child health. We also categorized whether the bill was signed into law. We
      examined associations between the outcomes and characteristics of the sponsoring
      legislators (gender, political party, terms served, chairpersonship of
      committees, legislative chamber, membership in the legislature's Black Caucus).
      RESULTS: During 1997 and 1998, legislators in the 3 study states introduced 9833
      bills (1234 in Colorado, 4905 in Louisiana, and 3694 in Michigan). Sixty-five
      bills (0.66%) related to child health issues. Child health bills comprised a
      significantly higher proportion of all legislation introduced by female
      legislators compared with male legislators (1.5% vs 0.5%, P <.001). Of bills
      introduced by Black Caucus members, 1.4% pertained to child health compared with
      0.59% of bills introduced by nonmembers (P <.01). In contrast, 0.23% of bills
      introduced by committee chairpersons pertained to child health versus 0.96% of
      bills introduced by nonchair legislators (P <.001). These associations remained
      statistically significant in multivariate analyses controlling for state effects.
      Whether child health bills were signed into law was not associated with other
      legislator characteristics. CONCLUSIONS: This study offers valuable insights
      about the different roles of women, Black Caucus members, and committee
      chairpersons in the state legislative process regarding children's health.

PMID- 15264944
TI  - Toward youth self-report of health and quality of life in population monitoring.
AB  - This paper addresses population monitoring of youth health and quality of life,
      including the concepts used, methodological and practical criteria for
      indicators, and existing surveys and measures. Current population surveys of
      youth generally focus on poor health, such as disability or health-risk
      behaviors. Although these are important end points, indicators of illness or risk
      do not reflect the health or life perspective of the majority of youth who do not
      experience health problems. The measures used to monitor youth health should be
      appropriate and sensitive to future needs and capture the perspectives of youths.
      Two potential concepts for this "scorecard" are self-perceived health and quality
      of life, which have been shown to be useful in adults. For youth, the quality of
      life framework seems particularly relevant as it incorporates both positive and
      negative aspects of health and well-being and also captures salient aspects of
      health other than physical health, such as sense of self, social relationships,
      environment and culture, and life satisfaction.

PMID- 15264945
TI  - Use of quality of life measures in clinical trials.
AB  - To be useful in clinical trials, quality of life (QOL) measures must meet basic
      criteria related to psychometric properties (reliability, validity, and
      sensitivity), length and acceptability to patients, and availability of parallel
      child and proxy versions. This paper examines the adequacy of several current
      measures, with special reference to childhood cancer. We identified 10 such
      measures of varying length, age-appropriateness, and content. We also discerned a
      number of obstacles to inclusion of QOL measures in trials. These include
      clinician bias, financial cost, and time required to inform families and to
      obtain informed consent from parents. We noted some methodological difficulties
      associated with measuring QOL over time. These include allowing for maturation
      and accounting for response shift, or children's propensity to change their
      internal standards for assessing QOL.

PMID- 15264946
TI  - The role and impact of gender and age on children's preferences for
      pediatricians.
AB  - OBJECTIVE: To determine the physician gender preferences of children and the
      consequences of meeting/not meeting children's preferences, both in their liking
      and feeling comfortable in talking with the pediatrician. METHODS: A convenience
      sample of 125 parent-child pairs completed surveys when coming for an outpatient
      visit to a university-sponsored, urban pediatric practice. RESULTS: Both
      adolescents and preadolescents (especially females) as young as 9 years of age
      expressed a gender preference for their physician. Meeting those preferences
      significantly affected how much children both liked and felt comfortable in
      talking with their physician. In young teen females, gender-preferred physicians
      are synonymous with gender-congruent physicians; yet although their preference
      for gender-congruent physicians increased in early adolescence, data indicated
      that their preference was often not met for several years to come. CONCLUSIONS:
      Liking and comfort with the pediatrician are not only desirable, but may also
      influence the doctor-patient relationship and young people's ability to develop
      health communication skills that they need as adults. These results, if
      validated, could also lead to a rethinking of parental dominance in the role of
      physician selection.

PMID- 15264947
TI  - Validating measures of pediatric health status, functional status, and health
      related quality of life: key methodological challenges and strategies.
AB  - OBJECTIVE: To describe key methodological challenges in the validation of
      measures of pediatric health status, functional status, and health-related
      quality of life (HRQOL) and ways to address them. METHODS: Validation strategies
      of measures of pediatric health status, functional status, and HRQOL were
      reviewed. RESULTS: Three key challenges were identified: 1) clarifying and
      testing measurement models; 2) measuring responsiveness to clinically meaningful
      change; and 3) considering data from multiple respondents. CONCLUSIONS: Research
      strategies to enhance validity of measures include specifying intended validity
      and measurement models, documenting sensitivity of measures to clinically
      meaningful change, and considering data from multiple informants.

PMID- 15264948
TI  - Factors associated with variations in parental social support in primary care
      pediatric settings.
AB  - OBJECTIVE: To examine social support (SS) among parents across
      sociodemographically distinct pediatric outpatient settings. METHODS: We
      conducted a cross-sectional, self-administered, anonymous parent survey in 3
      primary care sites in a Midwestern metropolitan area: inner-city health center,
      urban group practice, and suburban group practice. Participants were parents of
      children aged 6 weeks to 36 months. The main outcome measure was overall SS as
      measured by a previously validated 10-item instrument. Multivariate linear
      regression modeling was used to examine sociodemographic and health factors
      associated with overall SS scores. RESULTS: The study sample included 463
      parents. The strongest sources of SS were a significant other or spouse and
      parent's parent or grandparent. The range for overall SS was 0 to 20, with a mean
      score of 12.1 (SD, +/-4.2). Parents with overall SS in the lowest quartile (n =
      123) comprised 43% of parents at the inner-city health center compared with 23%
      of parents at the urban practice and 16% of parents at the suburban practice. In
      a multivariate model, factors associated with lower overall SS were race other
      than white or black, single or cohabiting marital status, poorer parental health,
      and parental depressive symptoms. CONCLUSIONS: Although parental SS was lowest in
      the most socioeconomically disadvantaged community in this sample, parents in all
      3 communities had widely varying levels of support. Providers may gain insights
      about parents at increased risk for low SS by asking about parents' own physical
      and mental health.

PMID- 15264949
TI  - A videotape to improve parental knowledge of lead poisoning.
AB  - BACKGROUND: Disadvantaged children are at high risk for lead poisoning. Their
      parents often have poor knowledge of lead poisoning and do not know how to
      prevent lead poisoning in their child. OBJECTIVE: To assess an educational
      videotape's impact on parental knowledge and behavior about lead poisoning.
      DESIGN: Prospective study by self-administered parental survey immediately before
      (pretest) and after (posttest 1) well visits and mailed 2-4 weeks later (posttest
      2). The intervention group watched the videotape immediately after the pretest.
      SETTING: Pediatric clinic in tertiary care hospital. PARTICIPANTS: Consecutive
      sample of parents of 6-month-old to 6-year-old children (n = 146). MAIN OUTCOME
      MEASURES: Survey included demographic questions, the shortened Chicago Lead
      Knowledge Test (sCLKT), and questions about parental behaviors. RESULTS: Mean
      pretest scores were 5.8 (SD, 2.8) and 5.3 (SD, 2.2), posttest 1 scores were 6.0
      (SD, 2.6) and 10.6 (SD, 2.1), and posttest 2 scores were 6.1 (SD, 2.8) and 9.5
      (SD, 2.8) of 14 in the control and intervention groups, respectively. Control and
      intervention group posttest 1 and posttest 2 score differences were statistically
      significant (P <.05). Intervention group parents reported more frequent washing
      of their child's hands (P <.05) and windows, walls, or floors at study completion
      (P <.05). CONCLUSIONS: The videotape significantly increased sCLKT scores and
      behaviors that may decrease children's risk of developing lead poisoning.
      Improvement persisted throughout the study period.

PMID- 15264950
TI  - Measuring child health: scientific questions, challenges, and recommendations.

PMID- 15264952
TI  - Culture, ethnicity, and linguistic issues in pediatric care: urgent priorities
      and unanswered questions.

PMID- 15264953
TI  - Child health disparities: framing a research agenda.

PMID- 15264954
TI  - Advocacy and child health.

PMID- 15264956
TI  - Measurements of the solar UVR protection provided by shade structures in New
      Zealand primary schools.
AB  - To reduce ultraviolet radiation (UVR) exposure during childhood, shade structures
      are being erected in primary schools to provide areas where children can more
      safely undertake outdoor activities. This study to evaluate the effectiveness of
      existing and purpose built shade structures in providing solar UVR protection was
      carried out on 29 such structures in 10 schools in New Zealand. Measurements of
      the direct and scattered solar UVR doses within the central region of the shade
      structures were made during the school lunch break period using UVR-sensitive
      polysulfone film badges. These measurements indicate that many of the structures
      had UVR protection factors (PF) of 4-8, which was sufficient to provide
      protection during the school lunch hour. However, of the 29 structures examined,
      only six would meet the suggested requirements of UVR PF greater than 15 required
      to provide all-day protection.

PMID- 15264957
TI  - Removing UV-A and UV-C radiation from UV-B fluorescent lamp emissions.
      Differences in the inhibition of photosynthesis in the marine alga Dunaliella
      tertiolecta using chromate versus cellulose acetate-polyester filters.
AB  - Ultraviolet-B (UV-B; 280-320 nm)-emitting lamps unavoidably emit ultraviolet-A
      (UV-A; 320-400 nm) and ultraviolet-C (UV-C; <280 nm) radiation. Short-wavelength
      blocking filters are generally used to limit the wave bands of UV under
      investigation. The widespread use of such filters means that all exposures to UV
      B radiation will have a significant UV-A component. Therefore, the physiological
      effects unique to UV-B exposure are difficult to clearly isolate. This study
      presents a method to remove the UV-A and UV-C "contamination" using a liquid
      potassium chromate (K(2)CrO(4)) filter, thus allowing more direct assessment of
      the effects of UV-B exposure. Cultures of the green marine alga Dunaliella
      tertiolecta were grown in the absence of UV radiation. Sunlamps supplied the UV
      radiation for a 24 h exposure (solar radiation was not used in this study). The
      UV radiation was filtered either by the standard method (i.e. cellulose acetate
      (CA) with polyester = Mylar controls) or by a liquid filter of potassium
      chromate. Photosynthetic responses were compared. Major decreases in the ratio of
      variable to maximal fluorescence in dark-adapted cells and photosynthetic
      capacity were observed in CA-filtered cultures, whereas no change was observed in
      cells exposed to the same UV-B flux with the UV-A removed by K(2)CrO(4). The use
      of a CA filter with a Mylar control does not link results unequivocally to UV-B
      radiation. Such results should be interpreted with caution.

PMID- 15264958
TI  - Willingness of eye care practices to evaluate children and accept Medicaid.
AB  - BACKGROUND: The willingness of eye care providers to evaluate children or to
      accept Medicaid may be a barrier to care for those with an abnormal screen.
      OBJECTIVES: To determine the proportion of eye care practices that would provide
      diagnostic evaluation for children and accept Medicaid payment and to evaluate
      the influence of child age and practice characteristics on provision of care or
      acceptance of Medicaid. METHODS: We conducted a telephone survey of 364 eye care
      practices in Michigan, which were randomly selected from telephone directories of
      26 rural and urban cities as defined by metropolitan statistical areas. RESULTS:
      The response rate was 93%. Most eye care practices, but more optometry-listed
      practices than ophthalmology-listed ones, would evaluate preschool-aged children
      (88% vs 73%; P <.01) or school-aged children only (11% vs 7%; P <.01). The
      proportion of practices willing to evaluate preschool-aged children was lower in
      urban cities compared with rural cities for optometry-listed (83% vs 96%; P <.01)
      and ophthalmology-listed practices (67% vs 93%; P <.01). Medicaid acceptance
      among practices that would evaluate children was higher among ophthalmology
      listed than optometry-listed practices (74% vs 59%; P =.01) and did not vary by
      urban or rural status. Practice size was not associated with willingness to
      provide care for children. However, among practices that would provide care for
      children, larger practice size was associated with increased odds of Medicaid
      acceptance in both optometry-listed and ophthalmology-listed practices.
      CONCLUSIONS: These findings contradict the perception that eye care for children
      is unavailable. More work is needed to understand the relationship of this
      availability with the accessibility of eye care.

PMID- 15264959
TI  - Parents' reports of barriers to care for children with special health care needs:
      development and validation of the barriers to care questionnaire.
AB  - OBJECTIVE: To describe the development and validation of the Barriers to Care
      Questionnaire (BCQ). METHODS: The 39-item BCQ was developed through review of the
      literature, focus groups, and cognitive interviews of Spanish- and English
      speaking parents of children with chronic health conditions. Barriers to care are
      conceptualized as a multidimensional construct consisting of pragmatics, health
      knowledge and beliefs, expectations about care, skills, and marginalization. The
      BCQ was field tested in 3 samples of children with special health care needs
      (CSHCN). RESULTS: Response rate for the field test was 77.2%. There were minimal
      missing data (0.08%), no floor effects, and minimal ceiling effects (3.8%, total
      scale). Internal consistency reliability (alpha) for the BCQ total scale was.95
      and subscale alpha ranged from.75 to.91. The BCQ total scale and subscales
      correlated in the expected direction with validated measures of primary care
      characteristics and health-related quality of life. BCQ scores were higher (fewer
      barriers) for children with a primary care physician and for those who reported
      no problems getting care or foregone care. CONCLUSION: The BCQ is a feasible,
      reliable, and valid instrument for measuring barriers to care for CSHCN. Its use
      may inform efforts to support consumer choice, enhance provider accountability,
      and spur quality improvement.

PMID- 15264960
TI  - Measurement of children's health.
AB  - Measuring child health has become a more pressing issue in the face of high rates
      of survival of childhood illnesses, often with residual chronic health conditions
      or impairments; the growing awareness of child behavioral and mental health
      morbidity; the focus on the importance of assessing therapeutic interventions and
      outcomes; and increased awareness of the multiple ways in which child health
      influences later adult health conditions. There is widespread belief that the
      perfect all-purpose measure can be developed and that researchers have not yet
      succeeded in doing so. This paper addresses three kinds of challenges to the
      measurement of child health that hamper the development of measures and make it
      likely that one size will not fit all. These include a series of fundamental
      underlying assumptions about health and its measurement, issues unique to
      assessing the health of children, and unresolved controversies that relate to the
      lens through which to assess child health.

PMID- 15264961
TI  - Smoking cessation counseling training for pediatric residents in the continuity
      clinic setting.
AB  - OBJECTIVE: To determine the effectiveness of a clinic-based smoking cessation
      counseling curriculum on pediatric resident confidence, knowledge, counseling
      skills, and provision of counseling. METHODS: Twenty-six residents at a pediatric
      residency program completed a new smoking cessation counseling curriculum as part
      of continuity clinic training. We assigned residents to 2 groups (study group, n
      = 12 vs control group, n = 14) on the basis of clinic site. We used a quasi
      experimental, crossover design with pre- and posttests for each group. Control
      group residents served as an initial control before the intervention crossover.
      Residents were tested at baseline and at completion of each group's intervention.
      Standardized patients measured resident provision of counseling and quality of
      counseling during resident continuity clinic. Knowledge and confidence were
      measured by a written exam and self-administered survey. Analysis of variance
      with a mixed design assessed overall group differences and group performances
      over time. RESULTS: There were no baseline differences between groups. Across
      time, there were significant differences between study-group and control-group
      residents for confidence (F [2, 48] = 11.82; P <.01), knowledge (F [2, 48] =
      6.24; P <.01), and provision of counseling (F [2, 48] = 3.60, P <.05) but not
      counseling skills (F [2, 48] = 2.44; P <.10). After each group's intervention,
      their confidence, knowledge, counseling skills, and inclusion of counseling
      increased significantly (P <.01 for all). CONCLUSIONS: Our findings suggest that
      a clinic-based curriculum in smoking cessation counseling can significantly
      increase knowledge, confidence, counseling skills, and provision of counseling.
      Future research should evaluate the long-term impact of such curricula on
      resident counseling behavior and patient outcomes.

PMID- 15264962
TI  - Evidence that school-age children can self-report on their health.
AB  - The value of obtaining children's reports about their health from questionnaires
      is a topic of considerable debate in clinical pediatrics and child health
      research. Evidence from the following areas can inform the debate: 1) studies of
      parent-child agreement or concordance about the child's health state, 2) basic
      research on the development of children's cognitive abilities, 3) cognitive
      interviewing studies of children's abilities to respond to questionnaires and of
      influences on their responses, 4) psychometric studies of child-report
      questionnaires, and 5) longitudinal research on the value of children's reports.
      This review makes a case for the utility of child rather than parent-proxy
      reports for many, though not all, applications. The review summarizes evidence in
      terms of the value and limitations of child questionnaire reports. Research
      demonstrates adequate understanding and reliability and validity of child reports
      of their health even at age 6, which increases after age 7 in general
      populations. The reliability of reports by children 8-11 years old is quite good
      on health questionnaires developed especially for this age group. Children's
      personal reports provide a viable means of monitoring internal experiences of
      health and distress during childhood and adolescence, which can enhance
      understanding about trajectories of health and development of illnesses.

PMID- 15264963
TI  - Parental mental health, childhood psychiatric disorders, and asthma attacks in
      island Puerto Rican youth.
AB  - OBJECTIVE: Previous research documents an association of poor parental mental
      health with asthma in children. This study aims to determine whether the
      associations between parental mental health problems and childhood asthma attacks
      persist after controlling for childhood anxiety and depression and other
      confounding factors. DESIGN/METHODS: A community household sample of youth ages 4
      to 17 years and their primary caregivers from the US Commonwealth of Puerto Rico
      was studied to determine the associations between parental mental health and
      childhood asthma attacks. Regression models that predicted asthma attacks in
      youth controlled for parental mental health problems, childhood anxiety and
      depression, zone of residence, and parents' age, education, and perception of
      poverty. RESULTS: After adjusting for children's depressive and anxiety disorders
      as well as other important confounders, associations between parental depression,
      suicide attempts, ataque de nervios, and history of mental health treatment and
      asthma attacks in offspring, by parental report, persisted. Additionally, the
      frequency of parental mental health problems was associated with children's
      asthma attacks. CONCLUSION: Parents with mental health problems were more likely
      to report histories of asthma attacks in their children compared with parents
      without mental health problems in Puerto Rico. These associations were not
      attributable to internalizing disorders in youth but persisted independent of
      childhood psychopathology and other confounding factors. Clinicians and
      researchers should recognize the relations between poor parental mental health
      and childhood asthma and explore the potential role of family psychosocial and
      behavioral factors related to the manifestation of the disease.

PMID- 15264964
TI  - Clinical effectiveness of atypical antipsychotics in dementia.

PMID- 15264965
TI  - Behavioral and psychological symptoms in dementia: the role of atypical
      antipsychotics.
AB  - Although cognitive dysfunction is the hallmark of dementia, behavioral and
      psychological symptoms of dementia (BPSD), such as psychosis, aggression, sleep
      disturbance, agitation, and mood disorders, develop in most elderly patients at
      some stage. These symptoms pose major difficulties in the day-to-day care of
      patients and are likely to impair the quality of life of both patient and
      caregiver. Patients exhibiting BPSD should be assessed in a detailed clinical
      interview to establish symptoms causing distress to the patient and/or caregiver.
      Several mood and behavior scales with good psychometric properties are available
      for patient evaluation. Initial intervention should focus on nonpharmacologic
      measures, and the quality of patient care should be optimized with potential
      physical, environmental, social, and psychiatric triggers being addressed where
      possible. Caregiver education, support, and behavioral training can also be
      effective in alleviating BPSD. However, pharmacologic intervention is necessary
      in many cases and includes use of antidepressants for mood disorders,
      anticonvulsants for nonpsychotic agitation, and antipsychotics for aggression,
      agitation, and psychotic symptoms. Conventional antipsychotics have shown modest
      benefit over placebo in the treatment of psychosis and agitation in dementia
      patients; however, they are associated with treatment-emergent side effects,
      particularly extrapyramidal symptoms (EPS). Atypical antipsychotics such as
      risperidone, olanzapine, and quetiapine are at least as effective as conventional
      antipsychotics, are better tolerated, and have a lower propensity for EPS. There
      are, however, significant differences between atypical agents with regard to
      receptor affinities and, therefore, side effect profiles. Patients' vulnerability
      to these side effects should be considered when making individual treatment
      decisions.

PMID- 15264966
TI  - Efficacy of atypical antipsychotics in elderly patients with dementia.
AB  - Pharmacotherapy in patients with dementia aims to improve distressing behavioral
      and psychological signs of dementia after nonpharmacologic interventions fail,
      without causing unacceptable side effects or exacerbating underlying cognitive
      impairment. We review data describing risperidone (3 published placebo-controlled
      trials), olanzapine (1 abstract regarding a placebo-controlled trial and a
      published placebo-controlled trial), quetiapine (1 published open-label trial and
      an abstract regarding a placebo-controlled trial), and aripiprazole (1 abstract
      regarding a placebo-controlled trial). For example, a 12-week study of
      risperidone in patients with Alzheimer's disease showed a dose-related
      improvement in psychosis and agitation. The frequency of extrapyramidal symptoms
      (EPS) was also significantly greater in patients receiving the highest doses. A 6
      week study of olanzapine showed greater improvement than placebo in
      agitation/aggression and psychosis with doses of 5 and 10 mg/day, but not 15
      mg/day, with side effects including gait disturbance and sedation at all doses. A
      52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly
      patients with psychosis suggested good tolerability with apparent behavioral
      benefit; EPS improved or remained unchanged in most patients. Limited data
      describing aripiprazole have shown inconclusive evidence regarding relief of
      psychosis in elderly patients with Alzheimer's disease-related dementia, with
      apparently good tolerability over the short term. It appears that, in the
      aggregate, atypical antipsychotics are efficacious for treatment of agitation in
      dementia, with less clear impact on psychosis, but their tolerability profiles
      clearly differ. The National Institute of Mental Health-funded Clinical
      Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease project
      will provide the first head-to-head comparisons of atypicals in dementia and will
      examine possible drug-drug differences between efficacy and effectiveness.

PMID- 15264967
TI  - Lewy body dementia: the litmus test for neuroleptic sensitivity and
      extrapyramidal symptoms.
AB  - Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a
      neurodegenerative disorder now considered to be the second most common cause of
      dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts
      for 20% to 34% of all dementia cases and is often underdiagnosed. Salient
      features of DLB include fluctuations in cognition, perceptual abnormalities
      (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include
      frequent falls, nighttime agitation, and depression. DLB symptomatology can be
      partly explained by the extensive destruction of dopaminergic and
      acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB
      patients are especially vulnerable to the antidopaminergic and anticholinergic
      actions of most conventional antipsychotics, which makes treatment of the
      psychotic symptoms of DLB extremely difficult. Patients are particularly
      sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially
      fatal complication of neuroleptic sensitivity, which affects approximately 50% of
      DLB patients. Therefore, a need exists for antipsychotic drugs with less
      propensity to induce EPS and reduced affinity for dopamine and acetylcholine
      receptors. Here we review studies evaluating the efficacy and tolerability of
      atypical antipsychotics for the treatment of psychoses associated with DLB.
      Olanzapine appears to be poorly tolerated, and risperidone has been associated
      with high risk of neuroleptic malignant syndrome. Clozapine use remains
      controversial because of its potent anticholinergic action and risk of
      agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations
      of DLB without causing neuroleptic sensitivity or increasing EPS. Hence,
      quetiapine is an attractive candidate for the treatment of psychoses in DLB and
      other dementias.

PMID- 15264969
TI  - Optimism, perceived risk of breast cancer, and cancer worry among a community
      based sample of women.
AB  - Optimism is frequently inversely associated with distress; however, less is known
      about the mechanisms underlying this relationship. Optimism can be defined as
      having a generalized positive expectancy about the future. The authors
      hypothesized that a specific expectancy might mediate the relationship between
      optimism and distress. That model was tested using perceived risk of breast
      cancer as a specific measure of expectancy and cancer worry as a measure of
      distress in a community-based sample of 1,366 women. It was hypothesized that
      optimism would be inversely associated with cancer worry and that perceived risk
      of breast cancer would mediate the relationship between optimism and cancer
      worry. Multiple regression analyses revealed that perceived risk partially
      mediated the relationship between optimism and cancer worry.

PMID- 15264968
TI  - The relationship between antipsychotic treatment and quality of life for patients
      with dementia living in residential and nursing home care facilities.
AB  - For any treatment, the impact on quality of life (QoL) is a key consideration.
      These issues are particularly important in the pharmacologic management of
      behavioral and psychological symptoms in patients with dementia (BPSD). Although
      these symptoms can be very distressing for some patients, the overall
      relationship of the symptoms with QoL is far less clear. In addition, although
      antipsychotic agents have moderate efficacy in the short- to medium-term
      management of these symptoms, it cannot be assumed that symptom resolution
      automatically equates with improved QoL. This is of particular concern in light
      of the adverse side effect profiles of many of these agents. Indeed, the only
      empirical study in this area conducted to date indicated that antipsychotics are
      associated with a worse QoL for nursing home patients. Unfortunately, none of the
      placebo-controlled trials of antipsychotics for the treatment of BPSD have
      included formal QoL measures, although preliminary evidence indicates that
      atypical antipsychotics such as quetiapine may result in QoL improvements. The
      inclusion of systematic QoL measures in future clinical trials is imperative in
      order to provide evidence to enable the clinician to make informed judgments
      regarding the potential benefits or risks of pharmacologic treatment for
      individual patients. In addition, such information will facilitate a better
      understanding of the likely factors that may contribute to the impact of
      treatment on QoL (e.g., side effects) and hence enable physicians to make
      rational treatment choices between different pharmacologic agents.

PMID- 15264970
TI  - Gender disparities in common sense models of illness among myocardial infarction
      victims.
AB  - Symptom attributions were contrasted between male and female myocardial
      infarction victims (N = 157) who were comparable on age, cardiac risk status,
      medical history, symptom presentation, and other variables. Women were less
      likely than men to attribute their prehospital symptoms to cardiac causes. In the
      context of hearing symptom attributions or advice from support persons, women
      were less likely than men to report receiving a cardiac attribution or advice to
      seek medical attention. Results have implications for how victim gender
      influences the lay interpretation of cardiac symptoms.

PMID- 15264971
TI  - Momentary mood and coping processes in TMD pain.
AB  - Temporomandibular dysfunction (TMD) pain, like many chronic pain problems,
      appears to be multiply determined. Patients with TMD pain of at least 6 months
      duration (N = 30) were administered questionnaires measuring dispositional coping
      styles and appraisals to explore the dynamic interactions of the pain and coping
      process. Patients were then issued handheld computers that prompted them to
      record their momentary pain and coping processes 4 times per day for 7 days.
      Hierarchical linear regression models using both the dispositional and momentary
      predictors indicated that momentary pain was a function both of dispositional
      tendency to catastrophize and of momentary measures of catastrophization, self
      efficacy, and mood states. Results were seen as supporting a situational model of
      intervention for chronic TMD pain.

PMID- 15264972
TI  - Psychosocial mediators of antiretroviral nonadherence in HIV-positive adults with
      substance use and mental health problems.
AB  - This study used data from 1,889 HIV-positive patients on antiretroviral (ARV)
      medications who participated in the HIV Cost and Services Utilization Study to
      investigate whether nonadherence to ARV medications among patients with mental
      health and substance use problems could be explained by difficulty getting and
      negative attitudes toward ARV medications, poor fit of the regimen with
      lifestyle, lack of instruction and cues for remembering the regimen from a health
      care provider, and poor support from others for taking ARV medications.
      Difficulty getting ARV medications and poor fit with lifestyle were significant
      mediators of nonadherence for patients with a probable psychiatric disorder.
      Difficulty getting medication was a mediator for heavy drinkers, and poor fit
      with lifestyle was a mediator for drug users who drank heavily. Further research
      is needed to identify and address the barriers to adherence in these populations.

PMID- 15264973
TI  - The effect of reinforcement or stimulus control to reduce sedentary behavior in
      the treatment of pediatric obesity.
AB  - Obese children were randomly assigned to a family-based behavioral treatment that
      included either stimulus control or reinforcement to reduce sedentary behaviors.
      Significant and equivalent decreases in sedentary behavior and high energy
      density foods, increases in physical activity and fruits and vegetables, and
      decreases in standardized body mass index (z-BMI) were observed. Children who
      substituted active for sedentary behaviors had significantly greater z-BMI
      changes at 6 (-1.21 vs. -0.76) and 12 (-1.05 vs. -0.51) months, respectively.
      Substitution of physically active for sedentary behaviors and changes in activity
      level predicted 6- and 12-month z-BMI changes. Results suggest stimulus control
      and reinforcing reduced sedentary behaviors are equivalent ways to decrease
      sedentary behaviors, and behavioral economic relationships in eating and activity
      may mediate the effects of treatment.

PMID- 15264974
TI  - Presurgery distress and specific response expectancies predict postsurgery
      outcomes in surgery patients confronting breast cancer.
AB  - Prior to scheduled surgery, patients frequently experience particularly high
      levels of distress and expect a variety of postsurgery symptoms. Surgery patients
      who confront breast cancer are no exception. It has been suggested that such
      presurgery distress and response expectancies are predictive of postsurgery
      outcomes. To test the contribution of presurgery distress and expectancies to
      common postsurgery symptom outcomes (pain, nausea, fatigue, and discomfort), 63
      female patients undergoing breast cancer surgery were recruited to a prospective
      study. Results indicated that presurgery distress uniquely contributed to
      patients' postsurgery nausea, fatigue, and discomfort; specific expectancies
      uniquely contributed to pain intensity, pain unpleasantness, and fatigue (ps <
      .05). Consistent with expectancy theory, associations between response
      expectancies and postsurgery outcomes were not due to presurgery distress.

PMID- 15264975
TI  - Individual differences in sensitivity to health communications: consideration of
      future consequences.
AB  - There are reliable individual differences in the extent to which people consider
      the long- and short-term consequences of their behaviors. Such differences,
      assessed by the Consideration of Future Consequences (CFC) Scale (A. Strathman,
      F. Gleicher, D. S. Boninger, & C. S. Edwards, 1994), are hypothesized to
      influence the impact of a persuasive communication. In an experimental study, the
      time frame of occurrence of positive and negative consequences of engaging in a
      new colorectal cancer-screening program was manipulated in a sample of two
      hundred twenty 50-69-year-old men and women. CFC moderated (a) the processing of
      short- versus long-term consequences and (b) the persuasive impact of the
      different communications on behavioral intentions. Low CFC individuals produced
      more positive thoughts and were more persuaded when positive consequences were
      short term and negative consequences were long term. The opposite was true for
      high CFC individuals.

PMID- 15264976
TI  - A randomized trial comparing the effects of self-help materials and proactive
      telephone counseling on teen smoking cessation.
AB  - We conducted a 2-arm randomized trial to test the efficacy of self-help materials
      with or without proactive telephone counseling to increase cessation among teen
      smokers. Teen smokers (N = 402) recruited from 11 shopping malls and 1 amusement
      park in the southeastern United States were randomized to 1 of 2 groups: written
      self-help material plus video; or written self-help material, video, and
      telephone counseling. Cessation rates based on 7-day point-prevalent abstinence
      for the self-help and counseling arms were 11% and 16%, respectively (p = .25),
      at 4 months postbaseline and 19% and 21%, respectively (p = .80), at 8 months
      postbaseline. Sustained abstinence, reflecting 7-day abstinence at both time
      points, in the self-help and counseling arms was 7% and 9% (p = .59). Results
      suggest that minimal self-help cessation approaches that target youth have
      comparable success to that shown among adult smokers. However, refinements in
      telephone-counseling approaches may be needed to achieve the success observed in
      adult populations.

PMID- 15264977
TI  - Conceptualization of disease timeline predicts posttreatment distress in breast
      cancer patients.
AB  - A sample of 69 breast cancer patients was assessed before and after cessation of
      treatment to determine the predictors of posttreatment distress. Patients were
      assessed approximately 6 weeks before completing chemotherapy treatment, 1 month
      after completing treatment, and 3 months after completing treatment. Results
      indicate that timeline beliefs are related to distress: Patients who
      conceptualize their cancer as a chronic or cyclic illness are more anxious,
      depressed, and worried about a recurrence than patients who conceptualize their
      cancer as an acute illness. These findings hold true even while controlling for
      disease stage. The way patients conceptualize their illness appears to be more
      influential in determining levels of posttreatment distress than objective
      indicators of the likelihood of recurrence.

PMID- 15264978
TI  - Social support, positive states of mind, and HIV treatment adherence in men and
      women living with HIV/AIDS.
AB  - Numerous studies have linked social support to better medication adherence among
      illness groups, but few have examined potential mechanisms for this relationship.
      Relationships were examined between social support, depression, positive states
      of mind (PSOM), and medication adherence among HIV positive men who have sex with
      men (n = 61) and women (n = 29) on highly active antiretroviral therapy.
      Depression and PSOM were evaluated as potential mediators of the relationship
      between support and adherence. Cross-sectional data showed that greater social
      support and PSOM related to better adherence whereas higher depression scores
      related to nonadherence. PSOM partially mediated the relationship between social
      support and adherence. PSOM may be an important mechanism through which social
      support is related to better medication adherence in this population.

PMID- 15264979
TI  - The motivating impact of informing women smokers of a link between smoking and
      cervical cancer: the role of coherence.
AB  - This research assessed the role of having a coherent explanation of the link
      between smoking and cervical cancer in motivating women to stop smoking. In the
      1st study, women were given a leaflet with either a detailed or a minimal
      explanation of the link or no leaflet. The leaflets were similarly effective at
      providing a coherent explanation. In a cross-sectional analysis, having a
      coherent explanation moderated the relationship between perceived vulnerability
      and intention: Higher perceived vulnerability to cervical cancer was associated
      with greater intention to quit smoking only amongst women with a more coherent
      explanation of the link between smoking and cervical cancer. This finding was
      replicated in a 2nd study. These results are consistent with H. Leventhal et
      al.'s (1997) self-regulatory model, which suggests that motivation to change
      behavior depends not only on perceiving a threat but also on having a coherent
      model linking the behavior with the threat.

PMID- 15264980
TI  - Mismatches in social support and psychosocial adjustment to breast cancer.
AB  - Emotional support is known to provide psychosocial benefits for women with breast
      cancer, but women can experience a mismatch between support that is wanted and
      support that is received from their personal supporter. The role of wanted and
      unwanted support in psychosocial adjustment was examined in 79 women recovering
      from breast cancer. Four distinct patterns of desired support actions were found
      using cluster analysis. Patterns of wanted support were not related to better or
      worse psychosocial adjustment. However, a misalignment of support between the
      provider and the receiver significantly influenced psychosocial adjustment, and
      unwanted but received support (support commission) was uniquely associated with
      poor psychosocial adjustment. Clinical interventions using the support instrument
      could help match support providers' actions to receivers' preferences.

PMID- 15264981
TI  - Questions raised by a reasoned action approach: comment on Ogden (2003).
AB  - In her critique of social cognition or reasoned action models, J. Ogden (see
      record 2003-05896-016) claimed that such models are not falsifiable and thus
      cannot be tested, that the postulated relations among model components are true
      by definition, and that questionnaires used to test the models may create rather
      than assess cognitions and thus influence later behavior. The authors of this
      comment challenge all 3 arguments and contend that the findings Ogden regarded as
      requiring rejection of the models are, in fact, consistent with them, that there
      is good evidence for the validity of measures used to assess the models' major
      constructs, and that the effect of completing a questionnaire on cognitions and
      subsequent behavior is an empirical question.

PMID- 15264982
TI  - Idiopathic pulmonary fibrosis: emerging concepts on pharmacotherapy.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrosing disease of the
      distal air spaces of the lung of unknown aetiology. IPF is usually fatal with a
      median survival of < 3 years. There are currently no effective
      pharmacotherapeutic agents for the treatment of IPF. In this review, unifying
      concepts on the pathogenesis of IPF based on understanding of host responses to
      tissue injury are presented. These host responses involve tightly regulated and
      contextually orchestrated inflammatory and repair processes. Dysregulation of
      either of these processes can lead to pathological outcomes. Fibrosis results
      from an exaggerated or dysregulated repair process that proceeds 'uncontrolled'
      even after inflammatory responses have subsided. Disease heterogeneity may arise
      when inflammation and repair are in different (dys)regulatory phases, thus
      accounting for regional disparity. Usual interstitial pneumonia (UIP), the
      histopathological correlate of clinical IPF, represents a more fibrotic tissue
      reaction pattern and for which anti-inflammatory agents are ineffective. Emerging
      'antifibrotic' drugs and strategies for UIP/IPF are discussed. The importance of
      accurately phenotyping a highly heterogeneous disease process that may require
      individualised and 'combined' therapies is emphasised.

PMID- 15264983
TI  - Advancements in the battle against severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease
      with a significant morbidity and mortality. The major clinical features include
      persistent fever, chills/rigor, myalgia, malaise, dry cough, headache and
      dyspnoea. Respiratory failure is the major complication of SARS and approximately
      20% of patients may progress to acute respiratory distress syndrome requiring
      invasive mechanical ventilatory support. However, the severity is much milder in
      infected young children. Treatment of SARS was empirical in 2003 due to our
      limited understanding of this new disease. Protease inhibitors
      (lopinavir/ritonavir) in combination with ribavirin may play a role as antiviral
      therapy in the early phase, whereas the role of IFN and systemic steroid in
      preventing immune-mediated lung injury deserves further investigation. Knowledge
      of the genomic sequence of the SARS coronavirus has facilitated the development
      of rapid diagnostic tests. In addition, other antiviral treatment, RNA
      interference, monoclonal antibody, synthetic peptides, and vaccines are being
      developed. This paper provides a review of the epidemiology, clinical features
      and possible treatment strategies of SARS.

PMID- 15264984
TI  - Treatment options in the management of necrotising fasciitis caused by Group A
      Streptococcus.
AB  - Invasive Group A Streptococcus (GAS) disease is a serious condition that has
      multiple manifestations. A particularly severe form of invasive GAS disease is
      necrotising fasciitis (NF). The case-fatality rate of GAS NF is approximately
      20%. Penicillin remains the antibiotic of choice when treating invasive GAS
      infections. Epidemiological studies have shown that clindamycin is effective in
      the treatment of deep infections that are caused by GAS. Clinicians should
      consider adding clindamycin to the beta-lactam antibiotic regimen when NF or
      myositis is present. Intravenous immunoglobulin appears to be a promising
      adjunctive therapy in the management of GAS NF. Consultations with surgeons and
      infectious disease specialists are imperative.

PMID- 15264985
TI  - Managing toxic shock syndrome with antibiotics.
AB  - Toxic shock syndrome (TSS) is a serious disorder with a worldwide prevalence of
      approximately 3/100,000 persons. TSS is mainly caused by Streptococcus pyogenes
      or Staphylococcus aureus. Thus, beta-lactam and lincosamides, such as
      clindamycin, are the first-line drugs. Yet, the mortality rate remains
      unacceptably high; highlighting the role of bacterial toxin-mediated activation
      of the inflammatory cascade in TSS pathogenesis. Further strategies should be
      targeted towards interfering with the interaction between bacterial toxins and
      host T cells. This paper aims to provide an overview of the epidemiology,
      pathomechanisms, and clinical presentation of TSS, and criteria for selecting
      drugs among available antibiotics.

PMID- 15264986
TI  - Chemotherapy for major food-borne trematodes: a review.
AB  - Food-borne trematode infections, caused by liver flukes (Clonorchis, Fasciola,
      Opisthorchis), lung flukes (Paragonimus) and intestinal flukes (Echinostoma,
      Fasciolopsis, heterophyids), are significant public health problems, most notably
      in Southeast Asia and the Western Pacific. Globally, it is estimated that > 40
      million people are infected among the 750 million people who live in endemic
      areas. The epidemiology of food-borne trematodiasis has changed over the past few
      decades, and now presents a dual picture. On the one hand, increasing numbers of
      infections are reported from non-endemic areas, and endemic areas are expanding
      due to larger areas utilised for aquaculture, domestic migration, declining
      socioeconomic conditions, lack of improved sanitation, and increasing
      availability of aquatic foods through wider distribution networks often without
      proper food inspections. On the other hand, social and economic advances in many
      Asian countries, going hand-in-hand with urbanisation, use of chemical
      fertilisers and, above all, the administration of safe, efficacious and
      inexpensive drugs, have significantly reduced the prevalence of food-borne
      trematode infections. In this review, the taxonomy, life cycle, and geographical
      distribution of the major food-borne trematodes, including issues of diagnosis
      and clinical disease manifestations, is summarised. The discovery, chemistry,
      pharmacological properties, safety, therapeutic efficacy and adverse effects of
      the current drugs of choice, namely praziquantel and triclabendazole, is then
      discussed. Recent advances on other drugs and contemporary investigations on
      novel compounds that might become important players in chemotherapy are
      highlighted. Finally, the need for research and development of new trematocidal
      drugs that - employed in concert with health education, improved sanitation and
      enhanced food safety - are key factors for sustainable control of food-borne
      trematodiasis, is highlighted.

PMID- 15264988
TI  - Available options in the management of non-typhi Salmonella.
AB  - Gastroenteritis, caused by Salmonella spp. is usually a self-limiting infection
      and does not require treatment. However, in some immunosuppressed patients (such
      as the newborn, the elderly, those with AIDS or neoplasms), there is a greater
      risk of developing a severe systemic infection, and in these cases, antibiotic
      treatment is recommended. Third-generation cephalosporins and fluoroquinolones
      are the most useful antibiotics in the treatment of these infections, although
      resistant strains are sometimes isolated. Therapeutic failures have been reported
      with fluoroquinolones in extra-intestinal infections caused by nalidixic acid
      resistant strains.

PMID- 15264987
TI  - An update on the medical management of listeriosis.
AB  - It is still not quite well understood why there is no optimal or even a
      satisfactory antibiotic therapy for listeriosis. Although almost all Listeria
      strains that induce sepsis, meningitis and encephalitis, as well as many other
      manifestations--in particular, in immunocompromised individuals--are susceptible
      to most of the common antibiotics, the cure rate is only approximately 70%. The
      most effective regimen still consists of a combination of an aminopenicillin
      (amoxicillin or ampicillin) plus an aminoglycoside. In vitro, this combination is
      bactericidal, whereas aminopenicillin alone only exerts a weak bactericidal
      activity against Listeriae. These antibiotics only poorly penetrate the
      cerebrospinal fluid and thus, only high doses given over a prolonged period of 2
      3 weeks are curative. Furthermore, Listeria monocytogenes belongs to the group of
      facultative intracellular bacteria, which means that a certain population is
      inaccessible for antibiotics. Theoretically, a drug which is endowed with
      bactericidal activity superior to that of ampicillin would be preferable.
      Furthermore, the candidate drug should easily cross the blood-brain barrier into
      the CNS, be able to accumulate within host cells, reach the cytoplasm and be
      active under these unusual conditions. Because of all these arguments, the new
      quinolones are of particular interest; but broad clinical data are still lacking.
      It is unclear as to whether antibiotics alone will be sufficient to increase the
      prognosis. Adjunctive therapy with immunomodulators, which are able to
      reconstitute the defective defence capacities, would presumably create the
      conditions necessary to finally resolve listeriosis.

PMID- 15264989
TI  - Diastolic heart failure: recognition, diagnosis and management.
AB  - A variety of community-based epidemiological studies have suggested that 30-50%
      of patients with heart failure symptoms appear to have preserved left ventricular
      (LV) systolic function when assessed by echocardiography or similar techniques
      suggesting 'diastolic heart failure' (DHF) as its cause. The prognosis of these
      patients is characterised by morbidity and mortality similar to, but less overt
      than, patients with systolic dysfunction. However, rates of readmission for
      symptom control are broadly similar in patients with DHF or in those with
      systolic impairment. Thus, there are many similarities in the portrayal of both
      systolic and DHF but equally; there are also many key differences. Certainly,
      while there are several successful therapies for patients with systolic heart
      failure, the management of patients with DHF is poorly defined. In this review,
      the gaps in current knowledge and practice, which is creating this therapeutic
      void will be addressed.

PMID- 15264990
TI  - Seborrhoeic dermatitis: current treatment practices.
AB  - Seborrhoeic dermatitis (SD) is a recurrent, chronic inflammation of the skin that
      occurs on sebum rich areas such as the face, scalp and chest, characterised by
      red scaly lesions. The are many studies indicating that Malassezia yeasts play an
      important role in the aetiology of this condition, most of the evidence for which
      comes from demonstrated responsiveness to treatment with antifungal agents. Its
      aetiology, however, is far from being resolved. Some believe that it is the
      immune response of the skin to the Malassezia that is the cause of the disease.
      Traditional treatments of SD have been the use of keratolytic agents or
      corticosteroids. Since the discovery of ketoconazole, a considerable amount of
      research has been focused on determining the efficacy of various antifungal
      agents. This article reviews clinical trial data on treatment options available
      for SD.

PMID- 15264991
TI  - Medical treatment of hidradenitis suppurativa.
AB  - Hidradenitis suppurativa (HS) is a common skin disease affecting an estimated 2%
      of the population. It causes significant symptoms and is notoriously difficult to
      treat. In this article, the current medical therapy is reviewed. At the present
      time, therapy appears to be based on an interpretation of the disease as either
      infectious or a form of acne. The understanding of the pathogenesis of HS
      suggests that these are not adequate models in order to understand the disease
      and this may explain the insufficiency of currently available medical treatment.
      The literature is sparse and there is a shortage of randomised, controlled
      trials. Three small, randomised, controlled trials have suggested that
      clindamycin, tetracycline and oestrogens and cyproteroneacetate may have an
      effect in some patients. Preceiving HS as an inflammatory skin disease suggests
      the use of general immunosuppressive drugs in the treatment of this condition.
      This approach, using both traditional immunosupressants and monoclonal
      antibodies, has been assessed in a small number of patients and appears to have
      some potential. However, the main source of evidence for this are case series and
      there is a strong need for more formal studies in this potentially debilitating
      disease.

PMID- 15264992
TI  - Paclitaxel for non-small cell lung cancer.
AB  - Paclitaxel, a tubulin-binding agent, is widely used for the treatment of non
      small cell lung cancer (NSCLC). The combination of paclitaxel and a platinum
      compound is an approved regimen for the treatment of advanced NSCLC. The dose
      limiting toxicity of paclitaxel is myelosuppression when administered on a
      prolonged infusion schedule, whereas neuropathy is more common with short
      infusions. Although the 3-weekly schedule of paclitaxel is the commonly utilised
      regimen for the treatment of advanced NSCLC, the weekly regimens appear to be
      associated with lesser myelosuppression and neuropathy. A randomised clinical
      trial is currently underway to compare the efficacy of the weekly versus 3-weekly
      regimen of paclitaxel, in combination with carboplatin for the treatment of
      advanced NSCLC. The radiosensitising effect of paclitaxel has led to its
      incorporation into multi-modality treatment of NSCLC patients in combination with
      thoracic radiation. Paclitaxel has also demonstrated synergistic interaction with
      several molecularly-targeted agents and is at present being evaluated in the
      neoadjuvant and adjuvant treatment settings for early stage NSCLC.

PMID- 15264993
TI  - Anagrelide: a decade of clinical experience with its use for the treatment of
      primary thrombocythaemia.
AB  - Primary thrombocythaemia (PT) is the most frequent among the rare chronic
      myeloproliferative disorders. Life expectancy is determined by thromboembolic and
      haemorrhagic complications, which can be prevented by cytoreductive therapy. For
      a long time, hydroxyurea has been considered as the therapeutic gold standard.
      However, hydroxyurea treatment is not lineage-specific, may not be tolerated
      because of adverse effects (skin, gastrointestinal tract) and is leukaemogenic
      when sequentially used with other DNA-targeting drugs. Hence, anagrelide was
      welcomed in 1988 when it was first described as being efficient at normalising
      elevated platelet counts, specific for megakaryocytes and non-mutagenic. Since
      then, anagrelide has been approved in the US and Canada (Agrylin), Shire
      Pharmaceuticals) as well as in Austria and other countries of the EU
      (Thromboreductin), AOP Orphan Pharmaceuticals). Clinical Phase III trials (PT1
      and ANAHYDRET) are underway to directly compare the efficacy and safety of
      anagrelide and hydroxyurea.

PMID- 15264994
TI  - Paroxetine in the treatment of generalised anxiety disorder.
AB  - Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment
      of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is
      characterised by excessive persistent anxiety and worry about a number of events
      and activities occurring on more days than not for at least 6 months. GAD is the
      most common anxiety disorder in primary care settings. Paroxetine was the second
      antidepressant to receive an FDA indication for the treatment of GAD. In contrast
      to benzodiazepines, which had been the mainstay of treatment for anxiety
      disorders for many years, antidepressants, such as paroxetine, are more effective
      for the psychic symptoms of anxiety, which include worry, tension, irritability
      and concentration difficulties, and carry a more tolerable and safe side effect
      profile.

PMID- 15264995
TI  - A review of the second-generation antihistamine ebastine for the treatment of
      allergic disorders.
AB  - Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation
      antihistamine. The use of ebastine is indicated in patients suffering from
      intermittent and persistent allergic rhinitis and chronic idiopathic urticaria.
      Ebastine 10 mg/day, appears as effective as other second-generation
      antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is
      indicated in patients with moderate and severe allergic symptoms. No
      cardiovascular effects of ebastine are described, although there is a
      pharmacokinetic interaction when ketoconazole or macrolides are co-administered.
      Ebastine has no relevant effects on the psychomotor performance. Even with
      ebastine 20 mg/day skilled performance does not appear to be impaired.
      Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used
      safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to
      be a safe, effective and well-tolerated second-generation antihistamine in the
      treatment of allergic rhinitis and chronic idiopathic urticaria.

PMID- 15264996
TI  - Fluticasone propionate/salmeterol for the treatment of chronic-obstructive
      pulmonary disease.
AB  - Chronic-obstructive pulmonary disease (COPD) is a global public health problem
      and its impact is increasing. Although only smoking cessation has been shown to
      alter the natural history of the disease, current treatment guidelines recommend
      the use of inhaled bronchodilators to decrease symptoms, improve lung function
      and quality of life and to prevent exacerbations. For a subset of patients with
      more severe disease, inhaled corticosteroids may also have a role in achieving
      these goals. Fluticasone propionate/salmeterol (Advair) or Seretide),
      GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator
      that is delivered by a dry-powder inhaler and was recently approved for use in
      COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and
      also appears to have important effects on the frequency of exacerbations and
      overall quality of life for some patients with COPD. Issues of patient selection
      as well as the pharmacology, efficacy and safety of the drug are discussed.

PMID- 15264998
TI  - New drugs for the prevention and treatment of migraine: topiramate and BIBN 4096
      BS.
AB  - Migraine is one of the leading causes of disability. Topiramate has multiple
      mechanisms and may reduce neurotransmission through the trigeminocervical complex
      to prevent migraine. In clinical trials for the prevention of migraine, the mean
      monthly migraine frequency decreased from 5.6 to 4.5 in the placebo group and
      larger decreases were observed with topiramate (100 mg/day, 5.8 to 3.5; 200
      mg/day, 5.1 to 3.0). However, topiramate use is associated with a high incidence
      of adverse events (paraesthesia, fatigue, anorexia, diarrhoea), which may limit
      the willingness of patients to use topiramate for the prevention of migraine.
      BIBN 4096 BS is a non-peptide calcitonin gene-related peptide-receptor antagonist
      that has recently been trialled in migraine attacks. The primary efficacy end
      point was the reduction of severe or moderate headache prior to treatment to mild
      or no headache at 2 h. This endpoint was achieved in 21 of 32 (66%) patients with
      BIBN 4096 BS 2.5 mg, compared to 27% of patients given placebo. Although BIBN
      4096 BS is a non-peptide, it is still administered intravenously, which will
      probably limit its use to medical centres.

PMID- 15264997
TI  - Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for
      chronic-obstructive pulmonary disease.
AB  - Tiotropium bromide is a quaternary ammonium compound structurally related to
      ipratropium and has recently been approved in the US for the long-term, once
      daily, maintenance treatment of bronchospasm associated with chronic-obstructive
      pulmonary disease (COPD). It is available in a dry powder form, where 18 microg
      [corrected] of the drug is inhaled once-daily through a device, the HandiHaler).
      The potency and long duration of effect of this anticholinergic bronchodilator
      result primarily from a prolonged blockade of the M1 and M3 muscarinic receptors
      in the airways and a relatively more rapid dissociation from the M2 receptor
      (which provides inhibitory feedback). Multiple studies of up to a duration of 1
      year have demonstrated its effectiveness as a bronchodilator for COPD, with a
      trough increase (measured approximately 24 h after administration of the drug) in
      forced expiratory volume in 1 s of approximately 0.12 l and a peak increase of
      approximately 0.25 l. Tiotropium inhalation also leads to a significant reduction
      in static lung volumes in hyperinflated patients with COPD; this probably
      contributes to the reduction in dyspnoea that is associated with long-term use of
      this maintenance bronchodilator. Regular use of the drug was associated with
      clinically meaningful increases in the Transitional Dyspnoea Index, which
      indicate reductions in dyspnoea associated with daily activities. Improvement in
      the respiratory-specific health status questionnaire, the St George's Respiratory
      Questionnaire component and total scores was also documented. Finally, pooled
      data from two 1-year studies and two 6-month studies documented 20 and 28%
      reductions in the number of exacerbations per patient per year. Side effects have
      been relatively minimal, with dry mouth the most common symptom, ranging 6 - 16%
      of patients and rarely leading to discontinuation of the study drug. Limited
      comparisons of efficacy with other bronchodilators are available. Once-daily
      tiotropium has been demonstrated to be clearly superior to ipratropium four times
      daily as a bronchodilator for COPD. Combined results from two studies comparing
      once-daily tiotropium to twice-daily inhalation of standard doses of salmeterol,
      indicate a magnitude of the bronchodilator response similar in the two drugs
      early in the study. However, by 6 months, the bronchodilator effect of tiotropium
      was somewhat greater than that of the long-acting beta-agonist. Preliminary data
      suggest that combining tiotropium with long-acting beta-agonists may produce
      additional bronchodilator action in COPD.

PMID- 15264999
TI  - A newly identified zona pellucida glycoprotein, ZPD, and dimeric ZP1 of chicken
      egg envelope are involved in sperm activation on sperm-egg interaction.
AB  - Fertilization begins with interaction between the sperm and the egg. The surface
      of the vertebrate oocyte is covered with the egg envelope, which is composed of
      ZP (zona pellucida) glycoproteins. We have identified two glycoproteins, ZP1/gp97
      and ZPC/gp42, as the major components of the chicken egg envelope. In the present
      study, another 42 kDa protein, designated ZPD, has been found as a new major
      component of the chicken egg envelope. ZPD was specifically released from the egg
      envelope by ultrasonication treatment without urea. ZPD cDNA was cloned using a
      chicken granulosa cell cDNA pool. The deduced amino acid sequence showed that
      preproprotein of ZPD is composed of 418 amino acid residues with four potential N
      glycosylation sites and includes a ZP domain, common in vertebrate ZP
      glycoproteins, and a transmembrane domain. ZPD belongs phylogenetically to a
      distinct group from known ZP glycoprotein subfamilies, ZPA, ZPB, and ZPC. In two
      dimensional gel electrophoresis ZPD proteins were identified to be several
      isoforms with different pI values between 5 and 7. ZP1, ZPC and the newly
      identified ZPD were confirmed to be the major components of chicken egg envelope
      by MS of proteolytic digests of whole egg envelope. The in vitro incubation of
      chicken sperm with calcium ionophore A23187 induced sperm activation, resulting
      in the fragmentation and release of a 41 kDa PNA (peanut agglutinin)-positive
      glycoprotein and the decrease or loss of sperm PNA-stainability. The incubation
      with ZPD and dimeric ZP1, but not ZPC and monomeric ZP1, also induced the
      decrease or loss of sperm PNA-stainability, suggesting the in vitro sperm
      activation by these ZP components. Collectively, ZPD might bind loosely to egg
      envelope matrix and play a key role in the sperm activation on avian sperm-egg
      interaction.

PMID- 15265000
TI  - Genetic and environmental factors modulating serum concentrations and activities
      of the antioxidant enzyme paraoxonase-1.
AB  - PON1 (paraoxonase-1) is an HDL (high-density lipoprotein)-associated enzyme
      capable of hydrolysing diverse substrates from OP (organophosphate) toxins to
      oxidized phospholipids. As such, it has been linked with both the prevention of
      OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified
      LDL (low-density lipoprotein). Mice deficient in PON1 are more susceptible to OP
      poisoning and oxidative stress and more prone to develop atherosclerosis than
      their wild-type siblings. There are a number of polymorphisms in the PON1 gene
      which affect serum PON1 activity and concentration. Many (but not all) studies in
      human populations have suggested that these polymorphisms may be a risk factor
      for atherosclerosis. The serum concentration of PON1 across the general
      population is highly variable and there is some debate as to whether genotype or
      phenotype (i.e. the quantity or quality of the enzyme) is most accurately
      associated with risk of disease development. What is clear is that factors
      influencing serum levels of PON1, be they genetic or environmental, will, in
      turn, affect the capacity of HDL to protect LDL from oxidation and, consequently,
      may be linked to atherosclerosis. This review will focus on mechanisms which
      determine the serum concentration of PON1, including gene expression and genetic
      polymorphisms, protein secretion and association with HDL, pharmacological and
      environmental factors.

PMID- 15265001
TI  - Weight loss leads to reductions in inflammatory biomarkers after a very-low
      carbohydrate diet and a low-fat diet in overweight men.
AB  - In recent years, it has become apparent that low-grade vascular inflammation
      plays a key role in all stages of the pathogenesis of atherosclerosis. Weight
      loss has been shown to improve blood inflammatory markers; however, it is unknown
      if weight-loss diets varying in macronutrient composition differentially affect
      inflammatory responses. The primary purpose of the present study was to compare a
      very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory
      biomarkers in overweight men. In a randomized cross-over design, 15 overweight
      men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight
      loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10%
      energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low
      fat and the very-low-carbohydrate diets resulted in significant decreases in
      absolute concentrations of hsTNF-alpha (high-sensitivity tumour necrosis factor
      alpha), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C
      reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1).
      There was no significant change in absolute sP-selectin (soluble P-selectin)
      concentrations after either diet. Normalized inflammatory values represented as
      the delta change per 1 kg reduction in body mass showed a significant difference
      between the two diets only for sP-selectin (P<0.05). In summary, energy
      restricted low-fat and very-low-carbohydrate diets both significantly decreased
      several biomarkers of inflammation. These data suggest that, in the short-term,
      weight loss is primarily the driving force underlying the reductions in most of
      the inflammatory biomarkers.

PMID- 15265002
TI  - Cathepsin K: a cysteine protease with unique kinin-degrading properties.
AB  - Taking into account a previous report of an unidentified enzyme from macrophages
      acting as a kininase, the ability of cysteine proteases to degrade kinins has
      been investigated. Wild-type fibroblast lysates from mice, by contrast with
      cathepsin K-deficient lysates, hydrolysed BK (bradykinin), and released two
      metabolites, BK-(1-4) and BK-(5-9). Cathepsin K, but not cathepsins B, H, L and
      S, cleaved kinins at the Gly4-Phe5 bond and the bradykinin-mimicking substrate
      Abz (o-aminobenzoic acid)-RPPGFSPFR-3-NO2-Tyr (3-nitrotyrosine) more efficiently
      (pH 6.0: kcat/K(m)=12500 mM(-1) x s(-1); pH 7.4: kcat/K(m)=6930 mM(-1) x s(-1))
      than angiotensin-converting enzyme hydrolysed BK. Conversely Abz-RPPGFSPFR-3-NO2
      Tyr was not cleaved by the Y67L (Tyr67-->Leu)/L205A (Leu205-->Ala) cathepsin K
      mutant, indicating that kinin degradation mostly depends on the S2 substrate
      specificity. Kininase activity was further evaluated on bronchial smooth muscles.
      BK, but not its metabolites BK(1-4) and BK(5-9), induced a dose-dependent
      contraction, which was abolished by Hoe140, a B2-type receptor antagonist.
      Cathepsin K impaired BK-dependent contraction of normal and chronic hypoxic rats,
      whereas cathepsins B and L did not. Taking together vasoactive properties of
      kinins and the potency of cathepsin K to modulate BK-dependent contraction of
      smooth muscles, the present data support the notion that cathepsin K may act as a
      kininase, a unique property among mammalian cysteine proteases.

PMID- 15265004
TI  - The crystal structure of microtubule-associated protein light chain 3, a
      mammalian homologue of Saccharomyces cerevisiae Atg8.
AB  - Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of
      yeast Atg8, plays an essential role in autophagy, which is involved in the bulk
      degradation of cytoplasmic components by the lysosomal system. Here, we report
      the crystal structure of LC3 at 2.05 A resolution with an R-factor of 21.8% and a
      free R-factor of 24.9%. The structure of LC3, which is similar to those of Golgi
      associated ATPase enhancer of 16 kDa (GATE-16) and GABAA receptor-associated
      protein (GABARAP), contains a ubiquitin core with two alpha helices, alpha1 and
      alpha2, attached at its N-terminus. Some common and distinct features are
      observed among these proteins, including the conservation of residues required to
      form an interaction among alpha1, alpha2 and the ubiquitin core. However, the
      electrostatic potential surfaces of these helices differ, implicating particular
      roles to select specific binding partners. Hydrophobic patches on the ubiquitin
      core of LC3, GABARAP and GATE-16 are well conserved and are similar to the E1
      binding surface of ubiquitin and NEDD8. Therefore, we propose that the
      hydrophobic patch is a binding surface for mammalian Atg7 similar to a ubiquitin
      like conjugation system. We also propose the functional implications of the
      ubiquitin fold as a recognition module of target proteins.

PMID- 15265003
TI  - Diminished synthesis of subunit a (ATP6) and altered function of ATP synthase and
      cytochrome c oxidase due to the mtDNA 2 bp microdeletion of TA at positions 9205
      and 9206.
AB  - Dysfunction of mitochondrial ATPase (F1F(o)-ATP synthase) due to missense
      mutations in ATP6 [mtDNA (mitochondrial DNA)-encoded subunit a] is a frequent
      cause of severe mitochondrial encephalomyopathies. We have investigated a rare
      mtDNA mutation, i.e. a 2 bp deletion of TA at positions 9205 and 9206
      (9205DeltaTA), which affects the STOP codon of the ATP6 gene and the cleavage
      site between the RNAs for ATP6 and COX3 (cytochrome c oxidase 3). The mutation
      was present at increasing load in a three-generation family (in blood:
      16%/82%/>98%). In the affected boy with severe encephalopathy, a homoplasmic
      mutation was present in blood, fibroblasts and muscle. The fibroblasts from the
      patient showed normal aurovertin-sensitive ATPase hydrolytic activity, a 70%
      decrease in ATP synthesis and an 85% decrease in COX activity. ADP-stimulated
      respiration and the ADP-induced decrease in the mitochondrial membrane potential
      at state 4 were decreased by 50%. The content of subunit a was decreased 10-fold
      compared with other ATPase subunits, and [35S]-methionine labelling showed a 9
      fold decrease in subunit a biosynthesis. The content of COX subunits 1, 4 and 6c
      was decreased by 30-60%. Northern Blot and quantitative real-time reverse
      transcription-PCR analysis further demonstrated that the primary ATP6--COX3
      transcript is cleaved to the ATP6 and COX3 mRNAs 2-3-fold less efficiently.
      Structural studies by Blue-Native and two-dimensional electrophoresis revealed an
      altered pattern of COX assembly and instability of the ATPase complex, which
      dissociated into subcomplexes. The results indicate that the 9205DeltaTA mutation
      prevents the synthesis of ATPase subunit a, and causes the formation of
      incomplete ATPase complexes that are capable of ATP hydrolysis but not ATP
      synthesis. The mutation also affects the biogenesis of COX, which is present in a
      decreased amount in cells from affected individuals.

PMID- 15265005
TI  - Fluctuation of chromatin unfolding associated with variation in the level of gene
      expression.
AB  - We examined whether spontaneous alteration of chromatin structure, if any,
      correlates with variation in gene expression. Gene activation is associated with
      changes in chromatin structure at different levels. Large-scale chromatin
      unfolding is one such change detectable under the light microscope. We
      established cell clones carrying tandem repeats (more than 50 copies spanning
      several hundred kb) of the GFP (green fluorescent protein)-ASK reporter genes
      driven by a tetracycline responsive promoter. These clones constitutively express
      the transcriptional transactivator. Flow cytometry and live-recording
      fluorescence microscopy revealed that, although fully activated by a saturating
      amount of doxycycline, GFP-ASK expression fluctuated in individual cell clones,
      regardless of the cell cycle stage. The GFP-ASK expression changed from lower to
      higher levels and vice versa within a few cell cycles. Furthermore, the levels of
      GFP-ASK expression were correlated with the degrees of chromatin unfolding of the
      integrated array as detected by FISH (fluorescent in situ hybridization). The
      chromatin unfolding was not coupled to a mitotic event; around one-third of the
      daughter-pairs exhibited dissimilar degrees of chromatin unfolding. We concluded
      that fluctuation of chromatin unfolding was likely to result in variation in gene
      expression, although the source of the fluctuation of chromatin unfolding remains
      to be studied.

PMID- 15265006
TI  - Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a
      protein assembly with multiple neuronal scaffold proteins in distinct modes of
      protein-protein interaction.
AB  - Hyperpolarization-activated cation currents, termed Ih, are non-uniformly
      distributed along dendritic arbors with current density increasing with
      increasing distance from the soma. The non-uniform distribution of Ih currents
      contributes to normalization of location-dependent variability in temporal
      integration of synaptic input, but the molecular basis for the graded HCN
      distribution remains to be investigated. The hyperpolarization-activated, cyclic
      nucleotide-gated cation channels (HCNs) underlie Ih currents and consist of four
      members (HCN1-HCN4) of the gene family in mammals. In this investigation, we
      report that HCN2 forms a protein assembly with tamalin, S-SCAM and Mint2 scaffold
      proteins, using several different approaches including immunoprecipitation of rat
      brain and heterologously expressing cell extracts and glutathione S-transferase
      pull-down assays. The PDZ domain of tamalin interacts with HCN2 at both the PDZ
      binding motif and the internal carboxy-terminal tail of HCN2, whereas binding of
      the PDZ domain of S-SCAM occurs at the cyclic nucleotide-binding domain (CNBD)
      and the CNBD-downstream sequence of the carboxy-terminal tail of HCN2. A protein
      assembly between HCN2 and Mint2 is formed by the interaction of the munc18
      interacting domain of Mint2 with the CNBD-downstream sequence of HCN2. The
      results demonstrate that HCN2 forms a protein complex with multiple neuronal
      scaffold proteins in distinct modes of protein-protein interaction.

PMID- 15265007
TI  - Nrf2 deficiency causes tooth decolourization due to iron transport disorder in
      enamel organ.
AB  - Rodents have brownish-yellow incisors whose colour represents their iron content.
      Iron is deposited into the mature enamel by ameloblasts that outline enamel
      surface of the teeth. Nrf2 is a basic region-leucine zipper type transcription
      factor that regulates expression of a range of cytoprotective genes in response
      to oxidative and xenobiotic stresses. We found that genetically engineered Nrf2
      deficient mice show decolourization of the incisors. While incisors of wild-type
      mice were brownish yellow, incisors of Nrf2-deficient mice were greyish white in
      colour. Micro X-ray imaging analysis revealed that the iron content in Nrf2
      deficient mouse incisors were significantly decreased compared to that of wild
      type mice. We found that iron was aberrantly deposited in the papillary layer
      cells of enamel organ in Nrf2-deficient mouse, suggesting that the iron transport
      from blood vessels to ameloblasts was disturbed. We also found that ameloblasts
      of Nrf2-null mouse show degenerative atrophy at the late maturation stage, which
      gives rise to the loss of iron deposition to the surface of mature enamel. Our
      results thus demonstrate that the enamel organ of Nrf2-deficient mouse has a
      reduced iron transport capacity, which results in both the enamel cell
      degeneration and disturbance of iron deposition on to the enamel surface.

PMID- 15265008
TI  - Interaction of Rho-kinase with myosin II at stress fibres.
AB  - Rho-kinase and myosin phosphatase cooperatively regulate the phosphorylation
      level of myosin light chain and are involved in the formation of stress fibres
      and smooth muscle contraction. Rho-kinase has been known to be localized at
      stress fibres, but little is known about the mechanism of its localization. Here
      we identified non-muscle myosin heavy chain IIA and IIB as the pleckstrin
      homology domain-interacting molecules by affinity column chromatography. The
      pleckstrin homology domain of Rho-kinase binds to myosin II directly in in vitro
      cosedimentation assay. The C-terminal region of the pleckstrin homology domain
      was important for this interaction, and the point mutations in the pleckstrin
      homology domain mutant (W1170A, W1340L) resulted in a decrease in the binding. We
      also found that the pleckstrin homology domain, but not the pleckstrin homology
      domain mutant (W1170A, W1340L), was localized at stress fibres in fibroblasts.
      These results indicate that Rho-kinase is localized at stress fibres through
      binding of the pleckstrin homology domain to myosin II.

PMID- 15265009
TI  - Transcriptional responses to epigallocatechin-3 gallate in HT 29 colon carcinoma
      spheroids.
AB  - Catechins have been reported to possess anti-cancer activity in vitro and in
      vivo. To identify target genes that may be involved in the anti-tumorigenic
      effect of catechins, gene expression profiles in adherent human HT 29 colon
      carcinoma cells, in HT 29 spheroids and in epigallocatechin-3 gallate (EGCG)
      treated HT 29 cells have been analysed by high-density oligonucleotide
      microarrays. Treatment of HT 29 cells with EGCG (2.5-50 microm) resulted in a
      dose-dependent inhibition of spheroid formation of HT 29 cells. Forty transcripts
      were induced at least twofold in 3-day-old spheroids relative to normal adherent
      cells using three replicates. Oncogenes like c-fos and c-jun are significantly up
      regulated in spheroids. We identified several signal transduction and
      proliferation genes which are down-regulated in response to EGCG treatment.
      Increase in the mRNA expression profile of c-Fos correlated well with protein
      levels in HT 29 spheroids whereas EGCG did not affect protein formation. In
      agreement with the DNA chip data, IQGAP2 protein was not increased in spheroids
      but protein formation was totally blocked in EGCG-treated cells. Interestingly,
      no change in expression of cytotoxic or apoptotic related genes has been observed
      in EGCG-treated cells. Our findings suggest that EGCG may exert its anti-cancer
      activity through modulation of expression of a number of genes that are involved
      in cell proliferation, cell-cell contacts and cell-matrix interactions.

PMID- 15265010
TI  - Suppression of melanogenesis by induction of endogenous intracellular
      metallothionein in human melanocytes.
AB  - Nitric oxide (NO) is a potent intercellular mediator of melanogenesis, whereas
      metallothionein (MT) is an inducible intracellular antioxidant that has been
      reported to scavenge NO. We investigated the existence and induction of MT in
      melanocytes, and its inhibitory effect on NO-induced melanogenesis. The
      expression of MT was detected in melanocytes, however, at a lower level than in
      keratinocytes, and its induction was possible by the addition of zinc chloride.
      Further, an NO-stimulated increase of tyrosinase activity in melanocytes was
      remarkably suppressed, when MT was induced prior to NO stimulation. Melanogenesis
      was also suppressed, when dexamethasone was used to induce MT. However, an NO
      stimulated increase of tyrosinase expression was not suppressed at the gene and
      protein level, when MT was induced in melanocytes. The same suppressive effect of
      melanogenesis was also observed, when alpha-melanocyte-stimulating hormone or
      endothelin-1 was used as a stimulator. Because these results implied a mechanism
      other than NO scavenging to explain the suppressive effect of MT induction on
      melanogenesis, the direct inhibition of tyrosinase by MT was examined. Melanosome
      fractions were prepared from melanocytes, whose melanogenesis was suppressed by
      the induction of MT. Tyrosinase suppression was observed in the melanosome
      fractions, which was neutralized by the addition of anti-MT antibody. These
      results suggest that MT induction may be effective to suppress melanogenesis
      stimulated by NO as well as other melanogens, and these suppressive effects might
      be due to a direct inhibition of tyrosinase activity in melanosome and not a
      scavenging effect of NO.

PMID- 15265011
TI  - Multilineage progression of genetically unstable tumor subclones in cutaneous T
      cell lymphoma.
AB  - Molecular analysis of solid malignant tumors has suggested multilineage
      progression of genetically unstable subclones during early stages of
      tumorigenesis as a common mechanism of tumor cell evolution. We have investigated
      whether multilineage progression is a feature of cutaneous T-cell lymphoma
      (CTCL). To identify individual tumor cell subclones, we determined the pattern of
      mutations within microsatellite DNA obtained from multiple histomorphologically
      confined tumor cell nests of mycosis fungoides (MF) and lymphomatoid papulosis
      (LyP) lesions. Tumor cells were isolated by laser microdissection, and
      allelotypes were determined at microsatellite markers D6S260, D9S162, D9S171,
      D10S215, TP53.PCR15, and D18S65. Nine cases of MF and one patient with anaplastic
      large cell lymphoma (ALCL) originating from LyP were analyzed at 277 different
      microdissected areas obtained from 31 individual lesions. Three specimens of
      cutaneous lichen planus microdissected at 26 areas served as the control tissue.
      Microsatellite instability in microdissected tissue [MSI(md-tissue)] was detected
      in tumor tissues of all CTCL patients. One hundred and fifty-seven of 469
      analyzed polymerase chain reaction (PCR) amplifications contained mutated
      microsatellite alleles (34%). In lichen planus, MSI(md-tissue) was seen in only
      four of 76 PCR products (5%) (P < 0.0001). The distribution of allelotypes in
      tumor cells from different disease stages was consistent with multilineage
      progression in five MF cases, as well as in the LyP/ALCL patient. Our results
      suggest that CTCL may evolve by multilineage progression and that tumor subclones
      in MF can be detected in early disease stages by mutation analysis of
      microsatellite DNA obtained from multiple microdissected areas.

PMID- 15265012
TI  - In vitro induction of matrix metalloproteinase-2 and matrix metalloproteinase-9
      expression in keratinocytes by boron and manganese.
AB  - Matrix metalloproteinase (MMP)-2 and MMP-9 are involved in keratinocyte migration
      and granulation tissue remodeling during wound healing. Thermal water cures are
      sometimes proposed as complementary treatment for accelerating healing of wounds
      resulting from burns and/or surgery, but their mechanisms of action remain
      unknown. Some thermal waters are rich in trace elements such as boron and
      manganese. Interestingly, clinical studies have shown the beneficial effects of
      trace elements such as boron and manganese for human wound healing. To try to
      specify the role of trace elements in cutaneous healing, the present study
      investigated the effects of these trace elements on the production of MMP-2 and
      MMP-9 by normal human keratinocytes cultured in vitro. Immunohistochemistry and
      Western blot showed that intracellular MMP-9 expression in keratinocytes was
      induced when incubated for 6 h with boron at 10 micro g/ml or manganese at 0.2
      micro g/ml. Moreover, gelatin zymography on keratinocyte supernatants showed an
      increase of gelatinase secretion after 24 h of incubation of keratinocytes with
      boron or manganese, regardless of concentration. Gelatinase secretion was not
      associated with keratinocyte proliferation induced by trace elements. Thus, our
      results suggest that boron and manganese could play a role in the clinical
      efficiency of thermal water on wound healing.

PMID- 15265013
TI  - Characterization of hair follicles induced in implanted, cultured rat
      keratinocyte sheets.
AB  - Cultured rat keratinocyte sheets form hair follicles in combination with rat
      vibrissa dermal papillae when they are transplanted subcutaneously in syngeneic
      rats and athymic mice. In the present study, the histologic details of these
      induced follicles were analyzed by preparing cultured sheets mixed with normal
      rat keratinocytes and green fluorescent protein (GFP)-transgenic rat
      keratinocytes. Histologic examination demonstrated that some induced follicles
      maintained their size and morphology for at least 18 weeks, whereas others
      decreased in size and others totally differentiated into cornified structures
      between 3 and 6 weeks. The percentage of the grafts with GFP-positive cells
      decreased during the same period. This finding suggests that some GFP-positive
      cells were transient-amplifying cells that turned into terminally differentiated
      cells and were lost during this period. Some large follicles and some small
      follicles maintained their hair-producing ability and the proliferative activity
      in their hair matrix for 18 weeks. In addition, one 6-week-old follicle contained
      label-retaining cells in the outer root sheath. Seven of 25 follicles induced
      from chimera epithelium contained both GFP-positive cells and GFP-negative cells.
      These results suggest that stem cells are present in the induced follicle and the
      induced follicle consists of polyclonally derived cells. The presence of early
      anagen-like large follicles at week 6 and 9 and a telogen-like small follicle at
      week 18 also suggests that hair-growth cycle phases proceeded in the induced
      follicles. In conclusion, the follicles induced in the cultured keratinocyte
      sheets maintained hair-producing ability and proliferative activity for at least
      18 weeks. This and the presence of label-retaining cells suggest that there are
      stem cells in the induced follicles, which seem to have a hair-growth cycle.

PMID- 15265014
TI  - The water-soluble extract of Illicium anisatum stimulates mouse vibrissae
      follicles in organ culture.
AB  - It is well known that reduced blood flow in the scalp is a cause of alopecia. We
      have shown previously that the extract of Illicium anisatum increases
      subcutaneous blood flow in mice. In the present study, we used an organ culture
      system to examine whether this extract promoted hair follicle elongation. B6C3HF1
      mouse vibrissae follicles were cultured in serum-free medium for 7 days at 31
      degrees C. Follicles treated with water-soluble (WS) extracts of the leaves,
      fruits and roots of Illicium anisatum or shikimic acid grew significantly longer
      than controls. In contrast, ethyl acetate-soluble (AS) extracts and n-hexane
      soluble (HS) extracts of the leaves, fruits and roots of the plant inhibited hair
      follicles and shaft growth. Fractionation of the WS fruit extract showed that the
      number 1 and number 2 fractions possessed hair follicle elongation activity.
      GC/MS analysis revealed that the number 1 fraction contained shikimic acid, and
      that the number 2 fraction was a mixture of many components including glycosides
      and polysaccharides. Reverse transcription-polymerase chain reaction analysis
      demonstrated that shikimic acid also induced mRNA expression of insulin-like
      growth factor-1, keratinocyte growth factor, and vascular endothelial growth
      factor in the hair follicles. These results suggest that the WS extract of
      Illicium anisatum promotes hair growth and may be a useful additive in hair
      growth products.

PMID- 15265015
TI  - Characterization of the expression and function of N-methyl-D-aspartate receptor
      in keratinocytes.
AB  - The N-methyl-D-aspartate (NMDA) receptor is expressed on neural tissue where it
      gates calcium ion entry upon stimulation. Using immunohistochemistry, it has been
      demonstrated in this study that the NMDAR1 receptor is also expressed on
      keratinocytes (KCs) in normal human skin and inflamed psoriatic skin in vivo.
      Furthermore, the NMDA receptor was functional as demonstrated by the ability of
      this receptor to trigger Ca++ influx in KCs. Incubation of cultured, human KCs
      with MK-801 decreases the cell growth and induces an increase in apoptosis. These
      findings demonstrate that the KC expression of NMDA receptor is a mechanism
      through which the influx of Ca++ into the cell can be regulated and suggest that
      the expression of this receptor may play a role in the regulation of KC growth
      and differentiation.

PMID- 15265016
TI  - N-methyl-D-aspartate receptors influence the intracellular calcium concentration
      of keratinocytes.
AB  - In the present study, the distribution of ionotropic glutamate receptors of the N
      methyl-D-aspartate (NMDA)-receptor type was immunohistochemically demonstrated in
      healthy human skin (n = 22) and healthy buccal mucosa (n = 20). Moreover, the
      intracellular calcium concentration of HaCaT-cells and native human keratinocytes
      were studied under the influence of the selective agonist NMDA and the selective
      NMDA-antagonist MK-801. Immunohistochemical imaging of NMDA receptors in healthy
      epidermis showed a positive reaction in the stratum basale, spinosum and
      granulosum, whereby the greatest expression was observed in the granular layer.
      In the mucosal preparations, the distribution of NMDA receptors was observed to
      be equal in all cell layers. In the cell culture (HaCaT-cells), NMDA
      concentrations between 25 microM and 1 mM resulted in a significant increase in
      the number of cells showing elevated intracellular calcium concentration. This
      effect could be significantly reduced by prior application of MK-801 (100 micro
      M). In supplementary tests on HaCaT-keratinocytes, blockade of the keratinocytic
      NMDA receptors with MK-801 suppressed the differentiation of the cells
      (expression of cytokeratin 10). The proliferation of cells was not influenced by
      NMDA. The investigations showed that glutamate receptors of the NMDA type have an
      influence on keratinocytic calcium concentration. This appears especially
      important for the differentiation of keratinocytes.

PMID- 15265017
TI  - Human T lymphocytes and mast cells differentially express and regulate extra- and
      intracellular CXCR1 and CXCR2.
AB  - CXCL8 plays a major role in cell recruitment to sites of inflammation. Apart from
      neutrophils, little is known, however, about the cellular distribution and
      regulation of CXCL8 receptors in cells involved in acquired and adaptive immune
      responses. In previous studies, we have demonstrated the extracellular expression
      and function of CXCR1/2 on mast cells and also detected an intracellular pool of
      CXCR1/2. Here, we have addressed the question of receptor regulation during
      stimulation of human mast cells (HMC-1 cell line) and have studied T cells in
      comparison. Cell permeabilization was performed to detect both surface and
      possible intracellular receptor pools. HMC-1 cells stained positive for both
      receptors on the cell surface (CXCR1, 50%; CXCR2, 51%) and also after cell
      permeabilization (CXCR1, 86%; CXCR2, 74%). Similarly, T cells exhibited both cell
      surface receptor expression (CXCR1, 30%; CXCR2, 23%) and higher total receptor
      expression (CXCR1, 50%; CXCR2, 36%), although overall values were lower than that
      in HMC-1 cells. On immunoblot, molecular weights of extra- and intracellular
      receptors on mast cells were the same, excluding altered receptor glycosylation.
      On stimulation with phorbol 12-myristate 13-acetate plus calcium ionophore, a
      time-dependent decrease of surface-membrane receptors was observed in both cell
      types, while total receptor remained the same, suggesting that receptor shedding
      is not involved. The kinetics of membrane receptor internalization and
      replenishment differed for the two cell types. Furthermore, receptor
      internalization was associated with decreased F-actin polymerization, a basic
      prerequisite for cell migration. These findings demonstrate for the first time
      the expression of extra- and intracellular CXCR1/2 receptors on T cells and
      delineate the dynamics of CXCR1/2 receptors on mast cells and T cells.
      Furthermore, they suggest a cell-type-specific and finely tuned regulation of
      chemokine responses at the receptor level in the context of inflammation.

PMID- 15265019
TI  - Detection of polymorphisms in the tumour necrosis factor alpha candidate gene in
      sheep.
AB  - Primers based on GenBank sequences of the ovine tumour necrosis factor (TNF)
      alpha gene were designed to amplify a 273-bp fragment comprising part of the
      fourth exon and the 3' untranslated region (UTR) of the ovine TNF-alpha gene.
      Five different single-strand conformational polymorphism (SSCP) patterns were
      detected in a number of unrelated animals and three different alleles were
      identified and sequenced. These alleles differed in one deletion and one single
      nucleotide polymorphism (SNP) and were named TNF*01, TNF*02 and TNF*03. These
      alleles corresponded to three sequences previously characterized by other groups.
      In the population analysis, no significant differences were found in the
      frequencies of the Latxa and Rasa breeds. This is the first description of
      allelic variation in the ovine TNF-alpha gene.

PMID- 15265020
TI  - Alternatively spliced transcripts of Fas mRNAs in feline lymphoid cells.
AB  - Fas belongs to the tumour necrosis factor receptor family and transduces the
      death signal after binding to the Fas ligand. Five feline lymphoma cell lines
      were shown, by reverse transcription-polymerase chain reaction, to express six
      species of Fas transcripts. Based on sequence comparison of these Fas transcripts
      with the genomic Fas gene, five of the six transcripts were found to be generated
      through alternative splicing and to encode five different Fas proteins lacking
      the transmembrane domain. We also detected such alternatively spliced transcripts
      in primary tumour tissues from cats with naturally occurring lymphoma. These
      results suggest a possible association of the alternatively spliced Fas variants
      with the pathogenesis of feline lymphoma.

PMID- 15265021
TI  - Cytokine gene polymorphisms and breast cancer susceptibility and prognosis.
AB  - Single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes
      are associated with differential levels of cytokine expression. We hypothesized
      that these SNPs might influence breast tumour development and progression by
      affecting the efficiency of the antitumour immune response and/or pathways of
      angiogenesis. A total of 144 female breast cancer patients and 263 cancer-free
      population controls were genotyped for the interleukin (IL)-1beta-511 (T/C), IL-6
      -174 (G/C), tumour necrosis factor (TNF)-alpha-308 (A/G), IL-10 -1082 (A/G), IL-8
      -251 (A/T) and vascular endothelial growth factor (VEGF) -1154 (A/G) SNPs, using
      amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and
      TaqMan (Applied Biosystems, Foster City, CA, USA) 5' nuclease assays for allelic
      discrimination. No significant associations were seen. Patient-control
      comparisons revealed a non-significant trend for association between the TNF
      alpha-308 GG genotype and breast cancer compared to controls (79.7 vs. 68.2%, P =
      0.03, Pc = 0.54). Stratification of the patient group according to the Nottingham
      Prognostic Index and individual prognostic factors revealed trends for
      association between IL-6 -174 GC and IL-8 -251 AA genotypes and markers of poor
      prognosis (P = 0.04, Pc = 0.72 and P = 0.02, Pc = 0.36, respectively). There were
      also trends for associations between VEGF -1154 AG and IL-1beta-511 TC genotypes
      and markers of good prognosis (P = 0.02, Pc = 0.36 and P = 0.05, Pc = 0.90,
      respectively). These results suggest that the role of cytokine promoter SNPs in
      both susceptibility to and prognosis in breast cancer requires further
      investigation in a larger study.

PMID- 15265022
TI  - Association between platelet endothelial cellular adhesion molecule 1 (PECAM
      1/CD31) polymorphisms and acute myocardial infarction: a study in patients from
      Sicily.
AB  - Adhesion of circulating cells to the arterial surface is among the first
      detectable events in atherogenesis. Cellular adhesion molecules, expressed by the
      vascular endothelium and by circulating leucocytes, mediate cell recruitment and
      their transendothelial migration. Platelet endothelial cellular adhesion molecule
      1 (PECAM-1/CD31), involved in this migration, has been associated with the
      developmental course of atherosclerosis. A few studies have investigated an
      association between coronary heart disease and single nucleotide polymorphisms
      (SNPs) located in functionally important domains of the PECAM-1/CD31 gene. In
      particular, Ser563Asn and Gly670Arg SNPs have been described as susceptibility
      factors involved in acute myocardial infarction (AMI) in the Japanese male
      population. To confirm these observations, we studied 96 male patients (mean age
      40 years; age range 20-46) affected by AMI and 118 healthy male controls (mean
      age 38 years, age range: 20-55), and analysed for the following PECAM-1/CD31
      SNPs: Val125Leu, Asn563Ser and Gly670Arg. The frequency of the Gly670Arg
      polymorphism was significantly higher in patients with AMI (58.9% vs. 48.3%; P =
      0.019), whereas the frequencies of the other two SNPs (Leu125Val and Ser563Asn)
      were not significantly different between patients and controls. By comparing the
      observed number of 670Arg/Arg genotypes in the patients with the expected number,
      calculated from the allele frequency in a healthy population, a significance of P
      = 0.02 (odds ratio, 2.04; 95% CI: 1.1-3.7) was obtained, supporting a recessive
      model of inheritance. Hence, the differences between patients and controls are
      significant, but relatively small. However, as AMI is a multifactorial disease,
      any single mutation will only provide a small or modest contribution to the risk,
      which also depends on environmental interaction. All in all, we believe that the
      results of the present study would add support to the role of pro/anti
      inflammatory genotypes in determining susceptibility or resistance to immune
      inflammatory diseases, including atherosclerosis.

PMID- 15265023
TI  - Effects of single nucleotide polymorphisms in the RANTES promoter region in
      healthy and HIV-infected indigenous Chinese.
AB  - We determined the occurrence of the single nucleotide polymorphisms (SNPs) 
      403A/G and -28C/G in the promoter region of RANTES in 1082 Chinese blood donors
      from northern and southern China and 249 HIV patients from southern China.
      Compared to healthy adults, Chinese AIDS patients had a significantly higher
      frequency of the -403G allele and haplotype I, -403G/-28C (P < 0.05), and a lower
      frequency of the -403A/A genotype (P < 0.01). Symptomatic patients had a higher
      frequency of the -28G allele and a lower frequency of the -28C/C genotype (P < or
      = 0.01). The plasma RANTES level was significantly lower in blood donors
      homozygous for haplotype I than in those who were homozygous for haplotypes II
      and III (P < 0.05). The frequency of the -403G allele was found to be higher in
      Chinese than in indigenous Africans, but lower than in Caucasians, Hispanics, and
      African Americans. The frequency of the -28G allele was comparable in Chinese and
      Japanese; this allele is rare in other ethnic groups. Results suggest that -403G
      may be associated with increased susceptibility to HIV infection, while -28G may
      be associated with advanced disease progression. The impact of SNPs on HIV
      infection appears to be unique in Chinese.

PMID- 15265024
TI  - HLA-DRB1 genotyping in patients with juvenile idiopathic arthritis in Taiwan.
AB  - The object of this study was to investigate whether there is an association
      between HLA-DRB1 alleles and the development of juvenile idiopathic arthritis
      (JIA) in Taiwan. HLA-DRB1 alleles were studied in 60 patients with JIA and 200
      healthy controls using polymerase chain reaction (PCR)/sequence-specific
      oligonucleotide probes (SSO). The frequency of HLA-DRB1*0405 in patients with JIA
      was found to be significantly higher than that in healthy controls [odds ratio
      (OR) 2.64, 95% confidence interval (CI) 1.01-6.91]. The DRB1*0405 allele was
      significantly associated with the development of both polyarthritis (OR 4.30, 95%
      CI 1.34-13.80) and oligoarthritis (OR 3.27, 95% CI 1.01-10.58). The frequency of
      HLA-DRB1*1502 was higher in Taiwanese JIA patients with systemic arthritis than
      in controls (OR 18.09, 95% CI 2.25-145.73). We conclude that, in Taiwan, HLA
      DRB1*0405 is associated with the development of polyarthritis and oligoarthritis
      in children, and HLA-DRB1*1502 is associated with the development of systemic
      arthritis.

PMID- 15265025
TI  - High nucleotide and amino acid sequence similarities in tumour necrosis factor
      alpha amongst Indian buffalo (Bubalus bubalis), Indian cattle (Bos indicus) and
      other ruminants.
AB  - Tumour necrosis factor-alpha (TNF-alpha) mRNA from Indian water buffalo (Bubalus
      bubalis) and Indian cattle (Bos indicus) was reverse transcribed and amplified
      using reverse transcriptase-polymerase chain reaction (RT-PCR). The nucleotide
      sequences of cDNAs were determined after cloning into pGEM-T-Easy vector
      (Promega, Madison, WI) and compared with reported nucleotide sequences of TNF
      alpha cDNA from other species. The nucleotide sequences of TNF-alpha from Indian
      cattle revealed significantly high similarities at nucleotide (99.2%) and amino
      acid (100%) levels with those of cattle (Bos taurus; Zebu). The sequences from
      buffalo had 98.4% nucleotide and 99.1% amino acid similarities with Indian
      cattle, indicating functional cross-reactivity. One amino acid deletion at
      position 63 and one substitution (A-->P) at position 64 were observed in buffalo
      compared with Indian cattle. The amino acid deletion at position 63 was predicted
      due to differences in pre-mRNA splicing.

PMID- 15265026
TI  - Nomenclature for factors of the HLA system, update April 2004.

PMID- 15265027
TI  - Nomenclature for factors of the HLA system, update May 2004.

PMID- 15265028
TI  - Nomenclature for factors of the HLA system, update June 2004.

PMID- 15265029
TI  - Biochemical and enzymological aspects of the symbiosis between the deep-sea
      tubeworm Riftia pachyptila and its bacterial endosymbiont.
AB  - Riftia pachyptila (Vestimentifera) is a giant tubeworm living around the volcanic
      deep-sea vents of the East Pacific Rise. This animal is devoid of a digestive
      tract and lives in an intimate symbiosis with a sulfur-oxidizing chemoautotrophic
      bacterium. This bacterial endosymbiont is localized in the cells of a richly
      vascularized organ of the worm: the trophosome. These organisms are adapted to
      their extreme environment and take advantage of the particular composition of the
      mixed volcanic and sea waters to extract and assimilate inorganic metabolites,
      especially carbon, nitrogen, oxygen and sulfur. The high molecular mass
      hemoglobin of the worm is the transporter for both oxygen and sulfide. This last
      compound is delivered to the bacterium which possesses the sulfur oxidizing
      respiratory system, which produces the metabolic energy for the two partners. CO2
      is also delivered to the bacterium where it enters the Calvin-Benson cycle. Some
      of the resulting small carbonated organic molecules are thus provided to the worm
      for its own metabolism. As far as nitrogen assimilation is concerned, NH3 can be
      used by the two partners but nitrate can be used only by the bacterium. This very
      intimate symbiosis applies also to the organization of metabolic pathways such as
      those of pyrimidine nucleotides and arginine. In particular, the worm lacks the
      first three enzymes of the de novo pyrimidine biosynthetic pathways as well as
      some enzymes involved in the biosynthesis of polyamines. The bacterium lacks the
      enzymes of the pyrimidine salvage pathway. This symbiotic organization
      constitutes a very interesting system to study the molecular and metabolic basis
      of biological adaptation.

PMID- 15265030
TI  - Distribution of the lipolysis stimulated receptor in adult and embryonic murine
      tissues and lethality of LSR-/- embryos at 12.5 to 14.5 days of gestation.
AB  - The lipolysis stimulated receptor (LSR) recognizes apolipoprotein B/E-containing
      lipoproteins in the presence of free fatty acids, and is thought to be involved
      in the clearance of triglyceride-rich lipoproteins (TRL). The distribution of LSR
      in mice was studied by Northern blots, quantitative PCR and immunofluorescence.
      In the adult, LSR mRNA was detectable in all tissues tested except muscle and
      heart, and was abundant in liver, lung, intestine, kidney, ovaries and testes.
      During embryogenesis, LSR mRNA was detectable at 7.5 days post-coitum (E7) and
      increased up to E17 in parallel to prothrombin, a liver marker. In adult liver,
      immunofluorescence experiments showed a staining at the periphery of hepatocytes
      as well as in fetal liver at E12 and E15. These results are in agreement with the
      assumption that LSR is a plasma membrane receptor involved in the clearance of
      lipoproteins by liver, and suggest a possible role in steroidogenic organs, lung,
      intestine and kidney). To explore the role of LSR in vivo, the LSR gene was
      inactivated in 129/Ola ES cells by removing a gene segment containing exons 2-5,
      and 129/Ola-C57BL/6 mice bearing the deletion were produced. Although
      heterozygotes appeared normal, LSR homozygotes were not viable, with the
      exception of three males, while the total progeny of genotyped wild-type and
      heterozygote pups was 345. Mortality of the homozygote embryos was observed
      between days 12.5 and 15.5 of gestation, a time at which their liver was much
      smaller than that of their littermates, indicating that the expression of LSR is
      critical for liver and embryonic development.

PMID- 15265031
TI  - Mitochondrial malate dehydrogenase from the thermophilic, filamentous fungus
      Talaromyces emersonii.
AB  - Mitochondrial malate dehydrogenase (m-MDH; EC 1.1.1.37), from mycelial extracts
      of the thermophilic, aerobic fungus Talaromyces emersonii, was purified to
      homogeneity by sequential hydrophobic interaction and biospecific affinity
      chromatography steps. Native m-MDH was a dimer with an apparent monomer mass of
      35 kDa and was most active at pH 7.5 and 52 degrees C in the oxaloacetate
      reductase direction. Substrate specificity and kinetic studies demonstrated the
      strict specificity of this enzyme, and its closer similarity to vertebrate m-MDHs
      than homologs from invertebrate or mesophilic fungal sources. The full-length m
      MDH gene and its corresponding cDNA were cloned using degenerate primers derived
      from the N-terminal amino acid sequence of the native protein and multiple
      sequence alignments from conserved regions of other m-MDH genes. The m-MDH gene
      is the first oxidoreductase gene cloned from T. emersonii and is the first full
      length m-MDH gene isolated from a filamentous fungal species and a thermophilic
      eukaryote. Recombinant m-MDH was expressed in Escherichia coli, as a His-tagged
      protein and was purified to apparent homogeneity by metal chelate chromatography
      on an Ni2+-nitrilotriacetic acid matrix, at a yield of 250 mg pure protein per
      liter of culture. The recombinant enzyme behaved as a dimer under nondenaturing
      conditions. Expression of the recombinant protein was confirmed by Western blot
      analysis using an antibody against the His-tag. Thermal stability studies were
      performed with the recombinant protein to investigate if results were consistent
      with those obtained for the native enzyme.

PMID- 15265032
TI  - Characterization of a Cry1Ac-receptor alkaline phosphatase in susceptible and
      resistant Heliothis virescens larvae.
AB  - We reported previously a direct correlation between reduced soybean agglutinin
      binding to 63- and 68-kDa midgut glycoproteins and resistance to Cry1Ac toxin
      from Bacillus thuringiensis in the tobacco budworm (Heliothis virescens). In the
      present work we describe the identification of the 68-kDa glycoprotein as a
      membrane-bound form of alkaline phosphatase we term HvALP. Lectin blot analysis
      of HvALP revealed the existence of N-linked oligosaccharides containing terminal
      N-acetylgalactosamine required for [125I]Cry1Ac binding in ligand blots. Based on
      immunoblotting and alkaline phosphatase activity detection, reduced soybean
      agglutinin binding to HvALP from Cry1Ac resistant larvae of the H. virescens YHD2
      strain was attributable to reduced amounts of HvALP in resistant larvae.
      Quantification of specific alkaline phosphatase activity in brush border membrane
      proteins from susceptible (YDK and F1 generation from backcrosses) and YHD2 H.
      virescens larvae confirmed the observation of reduced HvALP levels. We propose
      HvALP as a Cry1Ac binding protein that is present at reduced levels in brush
      border membrane vesicles from YHD2 larvae.

PMID- 15265033
TI  - N-Terminal segment of potato virus X coat protein subunits is glycosylated and
      mediates formation of a bound water shell on the virion surface.
AB  - The primary structures of N-terminal 19-mer peptides, released by limited trypsin
      treatment of coat protein (CP) subunits in intact virions of three potato virus X
      (PVX) isolates, were analyzed. Two wild-type PVX strains, Russian (Ru) and
      British (UK3), were used and also the ST mutant of UK3 in which all 12 serine and
      threonine residues in the CP N-terminal segment were replaced by glycine or
      alanine. With the help of direct carbohydrate analysis and MS, it was found that
      the acetylated N-terminal peptides of both wild-type strains are glycosylated by
      a single monosaccharide residue (galactose or fucose) at NAcSer in the first
      position of the CP sequence, whereas the acetylated N-terminal segment of the ST
      mutant CP is unglycosylated. Fourier transform infrared spectra in the 1000-4000
      cm(-1) region were measured for films of the intact and in situ trypsin-degraded
      PVX preparations at low and high humidity. These spectra revealed the presence of
      a broad-band in the region of valent vibrations of OH bonds (3100-3700 cm(-1)),
      which can be represented by superposition of three bands corresponding to tightly
      bound, weakly bound, and free OH groups. On calculating difference ('wet' minus
      'dry') spectra, it was found that the intact wild-type PVX virions are
      characterized by high water-absorbing capacity and the ability to order a large
      number of water molecules on the virus particle. This effect was much weaker for
      the ST mutant and completely absent in the trypsin-treated PVX. It is proposed
      that the surface-located and glycosylated N-terminal CP segments of intact PVX
      virions induce the formation of a columnar-type shell from bound water molecules
      around the virions, which probably play a major role in maintaining the virion
      surface structure.

PMID- 15265034
TI  - Mode of action of the microbial metabolite GE23077, a novel potent and selective
      inhibitor of bacterial RNA polymerase.
AB  - GE23077, a novel microbial metabolite recently isolated from Actinomadura sp.
      culture media, is a potent and selective inhibitor of bacterial RNA polymerase
      (RNAP). It inhibits Gram-positive (Bacillus subtilis) and Gram-negative
      (Escherichia coli) RNAPs with IC50 values (i.e. the concentration at which the
      enzyme activity is inhibited by 50%) in the 10(-8) m range, whereas it is not
      active on E. coli DNA polymerase or on eukaryotic (wheat germ) RNAP II (IC50
      values > 10(-4) m in both cases). In spite of its potent activity on purified
      bacterial RNAPs, GE23077 shows a narrow spectrum of antimicrobial activity on
      Gram-positive and Gram-negative bacteria. To investigate the molecular basis of
      this behaviour, the effects of GE23077 on macromolecular biosynthesis were tested
      in E. coli cells permeabilized under different conditions. The addition of
      GE23077 to plasmolyzed cells resulted in an immediate and specific inhibition of
      intracellular RNA biosynthesis, in a dose-response manner, strongly suggesting
      that cell penetration is the main obstacle for effective antimicrobial activity
      of the antibiotic. Biochemical studies were also conducted with purified enzymes
      to obtain further insights into the mode of action of GE23077. Interestingly, the
      compound displays a behaviour similar to that of rifampicin, an antibiotic
      structurally unrelated to GE23077: both compounds act at the level of
      transcription initiation, but not on the sigma subunit and not on the formation
      of the promoter DNA-RNAP complex. Tests on different rifampicin-resistant E. coli
      RNAPs did not show any cross-resistance between the two compounds, indicating
      distinct binding sites on the target enzyme. In conclusion, GE23077 is an
      interesting new molecule for future mechanistic studies on bacterial RNAP and for
      its potential in anti-infective drug discovery.

PMID- 15265035
TI  - Structural and functional analysis of ataxin-2 and ataxin-3.
AB  - Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3) are autosomal-dominantly
      inherited, neurodegenerative diseases caused by CAG repeat expansions in the
      coding regions of the genes encoding ataxin-2 and ataxin-3, respectively. To
      provide a rationale for further functional experiments, we explored the protein
      architectures of ataxin-2 and ataxin-3. Using structure-based multiple sequence
      alignments of homologous proteins, we investigated domains, sequence motifs, and
      interaction partners. Our analyses focused on presumably functional amino acids
      and the construction of tertiary structure models of the RNA-binding Lsm domain
      of ataxin-2 and the deubiquitinating Josephin domain of ataxin-3. We also
      speculate about distant evolutionary relationships of ubiquitin-binding UIM, GAT,
      UBA and CUE domains and helical ANTH and UBX domain extensions.

PMID- 15265036
TI  - Presence of membrane ecdysone receptor in the anterior silk gland of the silkworm
      Bombyx mori.
AB  - Nongenomic action of an insect steroid hormone, 20-hydroxyecdysone (20E), has
      been implicated in several 20E-dependent events including the programmed cell
      death of Bombyx anterior silk glands (ASGs), but no information is available for
      the mode of the action. We provide evidence for a putative membrane receptor
      located in the plasma membrane of the ASGs. Membrane fractions prepared from the
      ASGs exhibit high binding activity to [3H]ponasterone A (PonA). The membrane
      fractions did not contain conventional ecdysone receptor as revealed by Western
      blot analysis using antibody raised against Bombyx ecdysone receptor A (EcR-A).
      The binding activity was not solubilized with 1 m NaCl or 0.05% (w/v) MEGA-8,
      indicating that the binding sites were localized in the membrane. Differential
      solubilization and temperature-induced phase separation in Triton X-114 showed
      that the binding sites might be integrated membrane proteins. These results
      indicated that the binding sites are located in plasma membrane proteins, which
      we putatively referred to as membrane ecdysone receptor (mEcR). The mEcR
      exhibited saturable binding for [3H]PonA (Kd = 17.3 nm, Bmax = 0.82 pmol.mg(-1)
      protein). Association and dissociation kinetics revealed that [3H]PonA associated
      with and dissociated from mEcR within minutes. The combined results support the
      existence of a plasmalemmal ecdysteroid receptor, which may act in concert with
      the conventional EcR in various 20E-dependent developmental events.

PMID- 15265037
TI  - alpha-Synuclein-synaptosomal membrane interactions: implications for
      fibrillogenesis.
AB  - alpha-Synuclein exists in two different compartments in vivo-- correspondingly
      existing as two different forms: a membrane-bound form that is predominantly
      alpha-helical and a cytosolic form that is randomly structured. It has been
      suggested that these environmental and structural differences may play a role in
      aggregation propensity and development of pathological lesions observed in
      Parkinson's disease (PD). Such effects may be accentuated by mutations observed
      in familial PD kindreds. In order to test this hypothesis, wild-type and A53T
      mutant alpha-synuclein interactions with rat brain synaptosomal membranes were
      examined. Previous data has demonstrated that the A30P mutant has defective lipid
      binding and therefore was not examined in this study. Electron microscopy
      demonstrated that wild-type alpha-synuclein fibrillogenesis is accelerated in the
      presence of synaptosomal membranes whereas the A53T alpha-synuclein
      fibrillogenesis is inhibited under the same conditions. These results suggested
      that subtle sequence changes in alpha-synuclein could significantly alter
      interaction with membrane bilayers. Fluorescence and absorption spectroscopy
      using environment sensitive probes demonstrated variations in the inherent lipid
      properties in the presence and absence of alpha-synuclein. Addition of wild-type
      alpha-synuclein to synaptosomes did not significantly alter the membrane fluidity
      at either the fatty acyl chains or headgroup space, suggesting that synaptosomes
      have a high capacity for alpha-synuclein binding. In contrast, synaptosomal
      membrane fluidity was decreased by A53T alpha-synuclein binding with concomitant
      packing of the lipid headgroups. These results suggest that alterations in alpha
      synuclein-lipid interactions may contribute to physiological changes detected in
      early onset PD.

PMID- 15265038
TI  - Interaction of selenium compounds with zinc finger proteins involved in DNA
      repair.
AB  - As an essential element, selenium is present in enzymes from several families,
      including glutathione peroxidases, and is thought to exert anticarcinogenic
      properties. A remarkable feature of selenium consists of its ability to oxidize
      thiols under reducing conditions. Thus, one mode of action recently suggested is
      the oxidation of thiol groups of metallothionein, thereby providing zinc for
      essential reactions. However, tetrahedral zinc ion complexation to four
      thiolates, similar to that found in metallothionein, is present in one of the
      major classes of transcription factors and other so-called zinc finger proteins.
      Within this study we investigated the effect of selenium compounds on the
      activity of the formamidopyrimidine-DNA glycosylase (Fpg), a zinc finger protein
      involved in base excision repair, and on the DNA-binding capacity and integrity
      of xeroderma pigmentosum group A protein (XPA), a zinc finger protein essential
      for nucleotide excision repair. The reducible selenium compounds phenylseleninic
      acid, phenylselenyl chloride, selenocystine, ebselen, and 2
      nitrophenylselenocyanate caused a concentration-dependent decrease of Fpg
      activity, while no inhibition was detected with fully reduced selenomethionine,
      methylselenocysteine or some sulfur-containing analogs. Furthermore, reducible
      selenium compounds interfered with XPA-DNA binding and released zinc from the
      zinc finger motif, XPAzf. Zinc release was even evident at high
      glutathione/oxidised glutathine ratios prevailing under cellular conditions.
      Finally, comparative studies with metallothionein and XPAzf revealed similar or
      even accelerated zinc release from XPAzf. Altogether, the results indicate that
      zinc finger motifs are highly reactive towards oxidizing selenium compounds. This
      could affect gene expression, DNA repair and, thus, genomic stability.

PMID- 15265039
TI  - Protein transport into canine pancreatic microsomes: a quantitative approach.
AB  - Transport of presecretory proteins into the mammalian rough endoplasmic reticulum
      involves a protein translocase that comprises the integral membrane proteins
      Sec61alphap, Sec61betap, and Sec61gammap as core components. Electron microscopic
      analysis of protein translocase in rough microsomal membranes suggested that
      between three and four heterotrimeric Sec61p complexes form the central unit of
      protein translocase. Here we analyzed the stoichiometry of heterotrimeric Sec61p
      complexes present in cotranslationally active protein translocases of canine
      pancreatic microsomes and various other lumenal and membrane components believed
      to be subunits of protein translocase and to be involved in covalent
      modifications. Based on these numbers, the capacity for cotranslational transport
      was estimated for the endoplasmic reticulum of the human pancreas.

PMID- 15265040
TI  - Structural basis of charge transfer complex formation by riboflavin bound to 6,7
      dimethyl-8-ribityllumazine synthase.
AB  - The amino acid residue tryptophan 27 of 6,7-dimethyl-8-ribityllumazine synthase
      of the yeast Schizosaccharomyces pombe was replaced by tyrosine. The structures
      of the W27Y mutant protein in complex with riboflavin, the substrate analogue 5
      nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, and the product analogue 6
      carboxyethyl-7-oxo-8-ribityllumazine, were determined by X-ray crystallography at
      resolutions of 2.7-2.8 A. Whereas the indole system of W27 forms a coplanar pi
      complex with riboflavin, the corresponding phenyl ring in the W27Y mutant
      establishes only peripheral contact with the heterocyclic ring system of the
      bound riboflavin. These findings provide an explanation for the absence of the
      long wavelength shift in optical absorption spectra of riboflavin bound to the
      mutant enzyme. The structures of the mutants are important tools for the
      interpretation of the unusual physical properties of riboflavin in complex with
      lumazine synthase.

PMID- 15265041
TI  - Expression, purification and catalytic activity of Lupinus luteus asparagine beta
      amidohydrolase and its Escherichia coli homolog.
AB  - We describe the expression, purification, and biochemical characterization of two
      homologous enzymes, with amidohydrolase activities, of plant (Lupinus luteus
      potassium-independent asparaginase, LlA) and bacterial (Escherichia coli,
      ybiK/spt/iaaA gene product, EcAIII) origin. Both enzymes were expressed in E.
      coli cells, with (LlA) or without (EcAIII) a His-tag sequence. The proteins were
      purified, yielding 6 or 30 mg.L(-1) of culture, respectively. The enzymes are
      heat-stable up to 60 degrees C and show both isoaspartyl dipeptidase and l
      asparaginase activities. Kinetic parameters for both enzymatic reactions have
      been determined, showing that the isoaspartyl peptidase activity is the
      dominating one. Despite sequence similarity to aspartylglucosaminidases, no
      aspartylglucosaminidase activity could be detected. Phylogenetic analysis
      demonstrated the relationship of these proteins to other asparaginases and
      aspartylglucosaminidases and suggested their classification as N-terminal
      nucleophile hydrolases. This is consistent with the observed autocatalytic
      breakdown of the immature proteins into two subunits, with liberation of an N
      terminal threonine as a potential catalytic residue.

PMID- 15265042
TI  - On the mechanism of action of the antifungal agent propionate.
AB  - Propionate is used to protect bread and animal feed from moulds. The mode of
      action of this short-chain fatty acid was studied using Aspergillus nidulans as a
      model organism. The filamentous fungus is able to grow slowly on propionate,
      which is oxidized to acetyl-CoA via propionyl-CoA, methylcitrate and pyruvate.
      Propionate inhibits growth of A. nidulans on glucose but not on acetate; the
      latter was shown to inhibit propionate oxidation. When grown on glucose a
      methylcitrate synthase deletion mutant is much more sensitive towards the
      presence of propionate in the medium as compared to the wild-type and accumulates
      10-fold higher levels of propionyl-CoA, which inhibits CoA-dependent enzymes such
      as pyruvate dehydrogenase, succinyl-CoA synthetase and ATP citrate lyase. The
      most important inhibition is that of pyruvate dehydrogenase, as this affects
      glucose and propionate metabolism directly. In contrast, the blocked succinyl-CoA
      synthetase can be circumvented by a succinyl-CoA:acetate/propionate CoA
      transferase, whereas ATP citrate lyase is required only for biosynthetic
      purposes. In addition, data are presented that correlate inhibition of fungal
      polyketide synthesis by propionyl-CoA with the accumulation of this CoA
      derivative. A possible toxicity of propionyl-CoA for humans in diseases such as
      propionic acidaemia and methylmalonic aciduria is also discussed.

PMID- 15265043
TI  - Arginine ethylester prevents thermal inactivation and aggregation of lysozyme.
AB  - Arginine is a versatile additive to prevent protein aggregation. This paper shows
      that arginine ethylester (ArgEE) prevents heat-induced inactivation and
      aggregation of hen egg lysozyme more effectively than arginine or guanidine. The
      addition of ArgEE decreased the melting temperature of lysozyme. This data could
      be interpreted in terms of ArgEE binding to unfolded lysozyme, possibly through
      the ethylated carboxyl group, which leads to effective prevention of
      intermolecular interaction among aggregation-prone molecules. The data suggest
      that ArgEE could be used as an additive to prevent inactivation and aggregation
      of heat-labile proteins.

PMID- 15265044
TI  - A novel coupled enzyme assay reveals an enzyme responsible for the deamination of
      a chemically unstable intermediate in the metabolic pathway of 4-amino-3
      hydroxybenzoic acid in Bordetella sp. strain 10d.
AB  - 2-amino-5-carboxymuconic 6-semialdehyde is an unstable intermediate in the meta
      cleavage pathway of 4-amino-3-hydroxybenzoic acid in Bordetella sp. strain 10d.
      In vitro, this compound is nonenzymatically converted to 2,5-pyridinedicarboxylic
      acid. Crude extracts of strain 10d grown on 4-amino-3-hydroxybenzoic acid
      converted 2-amino-5-carboxymuconic 6-semialdehyde formed from 4-amino-3
      hydroxybenzoic acid by the first enzyme in the pathway, 4-amino-3-hydroxybenzoate
      2,3-dioxygenase, to a yellow compound (epsilonmax = 375 nm). The enzyme in the
      crude extract carrying out the next step was purified to homogeneity. The yellow
      compound formed from 4-amino-3-hydroxybenzoic acid by this purified enzyme and
      purified 4-amino-3-hydroxybenzoate 2,3-dioxygenase in a coupled assay was
      identified as 2-hydroxymuconic 6-semialdehyde by GC-MS analysis. A mechanism for
      the formation of 2-hydroxymuconic 6-semialdehyde via enzymatic deamination and
      nonenzymatic decarboxylation is proposed based on results of spectrophotometric
      analyses. The purified enzyme, designated 2-amino-5-carboxymuconic 6-semialdehyde
      deaminase, is a new type of deaminase that differs from the 2-aminomuconate
      deaminases reported previously in that it primarily and specifically attacks 2
      amino-5-carboxymuconic 6-semialdehyde. The deamination step in the proposed
      pathway differs from that in the pathways for 2-aminophenol and its derivatives.

PMID- 15265045
TI  - Calcium-independent cytoskeleton disassembly induced by BAPTA.
AB  - In living organisms, Ca2+ signalling is central to cell physiology. The Ca2+
      chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) has
      been widely used as a probe to test the role of calcium in a large variety of
      cell functions. Here we show that in most cell types BAPTA has a potent actin and
      microtubule depolymerizing activity and that this activity is completely
      independent of Ca2+ chelation. Thus, the depolymerizing effect of BAPTA is shared
      by a derivative (D-BAPTA) showing a dramatically reduced calcium chelating
      activity. Because the extraordinary depolymerizing activity of BAPTA could be due
      to a general depletion of cell fuel molecules such as ATP, we tested the effects
      of BAPTA on cellular ATP levels and on mitochondrial function. We find that BAPTA
      depletes ATP pools and affects mitochondrial respiration in vitro as well as
      mitochondrial shape and distribution in cells. However, these effects are
      unrelated to the Ca2+ chelating properties of BAPTA and do not account for the
      depolymerizing effect of BAPTA on the cell cytoskeleton. We propose that D-BAPTA
      should be systematically introduced in calcium signalling experiments, as
      controls for the known and unknown calcium independent effects of BAPTA.
      Additionally, the concomitant depolymerizing effect of BAPTA on both tubulin and
      actin assemblies is intriguing and may lead to the identification of a new
      control mechanism for cytoskeleton assembly.

PMID- 15265046
TI  - The role of the ESSS protein in the assembly of a functional and stable mammalian
      mitochondrial complex I (NADH-ubiquinone oxidoreductase).
AB  - The ESSS protein is a recently identified subunit of mammalian mitochondrial
      complex I. It is a relatively small integral membrane protein (122 amino acids)
      found in the beta-subcomplex. Genomic sequence database searches reveal its
      localization to the X-chromosome in humans and mouse. The ESSS cDNA from Chinese
      hamster cells was cloned and shown to complement one complementation group of our
      previously described mutants with a proposed X-linkage. Sequence analyses of the
      ESSS cDNA in these mutants revealed chain termination mutations. In two of these
      mutants the protein is truncated at the C-terminus of the targeting sequence; the
      mutants are null mutants for the ESSS subunit. There is no detectable complex I
      assembly and activity in the absence of the ESSS subunit as revealed by blue
      native polyacrylamide gel electrophoresis (BN/PAGE) analysis and polarography.
      Complex I activity can be restored with ESSS subunits tagged with either
      hemagglutinin (HA) or hexahistidine (His6) epitopes at the C-terminus. Although,
      the accumulation of ESSS-HA is not dependent upon the presence of mtDNA-encoded
      subunits (ND1-6,4 L), it is incorporated into complex I only in presence of
      compatible complex I subunits from the same species.

PMID- 15265047
TI  - Thermodynamic analysis of porphyrin binding to Momordica charantia (bitter gourd)
      lectin.
AB  - Owing to the use of porphyrins in photodynamic therapy for the treatment of
      malignant tumors, and the preferential interaction of lectins with tumor cells,
      studies on lectin-porphyrin interaction are of significant interest. In this
      study, the interaction of several free-base and metalloporphyrins with Momordica
      charantia (bitter gourd) lectin (MCL) was investigated by absorption
      spectroscopy. Difference absorption spectra revealed that significant changes
      occur in the Soret band region of the porphyrins on binding to MCL. These changes
      were monitored to obtain association constants (Ka) and stoichiometry of binding.
      The tetrameric MCL binds four porphyrin molecules, and the stoichiometry was
      unaffected by the presence of the specific sugar, lactose. In addition, the
      agglutination activity of MCL was unaffected by the presence of the porphyrins
      used in this study, clearly indicating that porphyrin and carbohydrate ligands
      bind at different sites. Both cationic and anionic porphyrins bind to the lectin
      with comparable affinity (Ka =10(3)-10(5) m(-1)). The thermodynamic parameters
      associated with the interaction of several porphyrins, obtained from the
      temperature dependence of the Ka values, were found to be in the range: DeltaH
      degrees = -98.1 to -54.4 kJ.mol(-1) and DeltaS degrees =-243.9 to -90.8 J.mol(
      1).K(-1). These results indicate that porphyrin binding to MCL is governed by
      enthalpic forces and that the contribution from binding entropy is negative.
      Enthalpy-entropy compensation was observed in the interaction of different
      porphyrins with MCL, underscoring the role of water structure in the overall
      binding process. Analysis of CD spectra of MCL indicates that this protein
      contains about 13%alpha-helix, 36%beta-sheet, 21%beta-turn, and the rest
      unordered structures. Binding of porphyrins does not significantly alter the
      secondary and tertiary structures of MCL.

PMID- 15265049
TI  - Blockade of CGRP receptors in the intracranial vasculature: a new target in the
      treatment of headache.
AB  - In primary headaches, there is a clear association between the headache and the
      release of calcitonin gene-related peptide (CGRP) but not with any of the other
      neuronal messengers. The purpose of this review is to describe the role of CGRP
      in the intracranial circulation and to elucidate a possible role for a specific
      CGRP receptor antagonist in the treatment of primary headaches. Acute treatment
      with a 5-HT(1B/1D) agonist (triptan) results in alleviation of the headache and
      normalization of the cranial venous CGRP levels, in part due to a presynaptic
      inhibitory effect on sensory nerves. The central role of CGRP in migraine and
      cluster headache pathophysiology has led to the search for small molecule CGRP
      antagonists with few cardiovascular side-effects. The initial pharmacological
      profile of such a group of compounds has recently been disclosed. One of these
      compounds has been found to be efficacious in the relief of acute attacks of
      migraine.

PMID- 15265050
TI  - Platelet-activating factor (PAF) in internal jugular venous blood of migraine
      without aura patients assessed during migraine attacks.
AB  - The aim of the study was to verify the production of PAF and the activity of PAF
      acetyl-hydrolase (PAF-AH), the enzyme involved in the catabolism of this
      phospholipid mediator, in migraine attacks. Their levels were determined during
      migraine crises in serial samples of internal jugular venous blood taken from
      five migraine patients without aura, who were admitted to the hospital during the
      crises. Internal jugular venous blood samples were taken immediately after
      catheter insertion at 1, 2, and 4 h after attack onset, and within 2 h from its
      cessation. PAF was purified by high-performance liquid chromatography (HPLC) and
      determined by radioimmunoassay method. The enzymatic activity of PAF-AH was
      measured by reverse-phase HPLC, based on the derivatization with 7
      diethylaminocoumarin-3-carbonylazide. In the internal jugular venous blood of
      migraine patients without aura (MO), an increase was observed in PAF levels,
      which was already evident at the time of catheter insertion (885.6 +/- 82.8) and
      at the first hour (868.4 +/- 65.24) (ANOVA: P < 0.0001). PAF levels remained
      elevated through the second (746.8 +/- 82.95), fourth (700.6 +/- 34.93) and sixth
      hours (644.4 +/- 42.85), and then decreased at the end of the attack, reaching
      levels significantly lower than those measured at the time of catheter insertion
      (565.5 +/- 38.34). The activity of PAF-AH showed an opposite trend with higher
      values at the first hour and significantly lower values at the second and fourth
      hours from the beginning of the migraine attack (ANOVA: P < 0.02). The increased
      production of PAF may account for persistent platelet activation during migraine
      crises, even in the presence of an increased production of nitric oxide (NO) end
      products which, on the other hand, should instead intervene in counteracting and
      limiting platelet activation. Potential sources of PAF production are the
      endothelial cells from cerebral vessels, stimulated by trigeminal neuropeptides,
      platelets themselves, and mast cells, as suggested by the neurogenic inflammation
      model.

PMID- 15265051
TI  - Cluster headache in the Taiwanese -- a clinic-based study.
AB  - Cluster headache has not been fully investigated in Asians. One hundred and four
      patients (90M/14F; mean age 39.2 +/- 12.2 years) with cluster headache were
      recruited from two major headache clinics in Taiwan. They filled out a structured
      cluster headache questionnaire. All participants were diagnosed to have episodic
      cluster headache. Mean age of onset was 26.9 years; mean latency of diagnosis was
      8.1 years. A trend of decrease in male/female ratio with time was noted. Seventy
      three percent were ex- or current smokers (M: 79%, F: 36%). Restlessness was
      reported by 51% patients. Only 1 patient (1%) reported visual aura. Patients
      responded well to standard acute and prophylactic treatment. The monthly
      incidence of cluster period was inversely related to sunshine duration. Compared
      to Western series, our patients were different in several aspects including the
      absence of chronic cluster headaches and a low prevalence of restlessness and
      aura. Racial and geographical factors might contribute to these discrepancies.

PMID- 15265052
TI  - A randomized, double blind study of the prophylactic effect of hyperbaric oxygen
      therapy on migraine.
AB  - In a double blind, placebo-controlled study to assess the prophylactic effect of
      hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a
      treatment group receiving three sessions of hyperbaric oxygen, or a control group
      receiving three hyperbaric air treatments. The patients were instructed to keep a
      standardized migraine diary for eight weeks before and after the treatment.
      Thirty-four patients completed the study. Our primary measure of efficacy was the
      difference between pre- and post-treatment hours of headache per week. The
      results show a nonsignificant reduction in hours of headache for the hyperbaric
      oxygen group compared to the control group. Levels of endothelin-1 in venous
      blood before and after treatment did not reveal any difference between the
      hyperbaric oxygen and control groups. We conclude that the tested protocol does
      not show a significant prophylactic effect on migraine and does not influence the
      level of endothelin-1 in venous blood.

PMID- 15265053
TI  - Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective
      small molecule calcitonin gene-related peptide receptor antagonist, following
      single intravenous administration in healthy volunteers.
AB  - BIBN 4096 BS ([R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1
      piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2
      oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is
      the first selective, highly potent, small molecule, nonpeptide calcitonin gene
      related peptide (CGRP) receptor antagonist, which has been developed for the
      treatment of acute migraine. The objective of this study was to obtain
      information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS
      following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1,
      2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of
      single-centre, double-blind (within dose levels), placebo-controlled, randomized,
      single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG,
      laboratory tests and forearm blood flow did not reveal any clinically relevant,
      drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41
      volunteers after BIBN 4096 BS compared to five AEs reported by four of 14
      volunteers after placebo. Approximately two-thirds of all AEs related to active
      treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were
      confined to the three BIBN 4096 BS-treated females, and consisted mainly of
      transient and mild paresthesias. Paresthesias were the single most frequent AE,
      whereas fatigue was the AE which occurred in the highest number of subjects. Only
      two AEs were of moderate intensity, all remaining AEs were of mild intensity. No
      serious AEs were reported. The local tolerability after intravenous
      administration was good. In summary, intravenously administered BIBN 4096 BS
      revealed a very favourable safety profile over the dose range tested in both
      genders. Generally well tolerated at all dose levels, it was of satisfactory
      tolerability in female subjects at the highest dose of 10 mg. The plasma
      concentration-time courses of BIBN 4096 BS showed multicompartmental disposition
      characteristics. Mean maximum concentration (Cmax) values appeared to be dose
      proportional. Based on the results from the two high dose levels (5 and 10 mg)
      with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma
      clearance (CL) of approximately 12 l/h and an apparent volume of distribution at
      steady state (Vss) of approximately 20 l, resulting in a terminal half-life
      (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a
      coefficient of variation of approximately 45% based on the area under the plasma
      concentration-time curve (AUC) values. The mean renal clearance (CLR) was
      approximately 2 l/h, suggesting that renal excretion plays only a minor role in
      the elimination of unchanged BIBN 4096 BS.

PMID- 15265054
TI  - Differences of anti-nociceptive mechanisms of migraine drugs on the trigeminal
      pain processing during and outside acute migraine attacks.
AB  - The aim of this study was to investigate central anti-nociceptive mechanisms of
      i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients
      and healthy subjects using the 'nociceptive' blink reflex (nBR). Twenty-eight
      migraine patients received ASA (n = 14, 1000 mg i.v) or ZOL (n = 14, 5 mg p.o)
      during the acute migraine attack and interictally. Thirty healthy subjects
      received either ASA or ZOL vs. placebo using a double blind cross over design.
      nBR was recorded in all patients and subjects before, 60 and 90 min after
      treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both
      ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the
      acute attack but not interictally. The data suggest, that the anti-nociceptive
      effects of migraine drugs on the trigeminal nociceptive processing are different
      during and outside an acute migraine attack.

PMID- 15265055
TI  - Interictal lack of habituation of mismatch negativity in migraine.
AB  - The aim was to study mismatch negativity features and habituation during the
      interictal phase of migraine. In migraine patients, a strong negative correlation
      has been found between the initial amplitude of long latency auditory-evoked
      potentials and their amplitude increase during subsequent averaging. We studied
      12 outpatients with a diagnosis of migraine without aura recorded in a headache
      free interval and 10 gender- and age-matched healthy volunteers not suffering
      from any recurrent headache. The experiment consisted of two sequential blocks of
      2000 stimulations, during which 1800 (90%) recordings for standard tones and 200
      (10%) for target tones were selected for averaging. The latency of the N1
      component was significantly increased in migraine patients in respect of controls
      in both the first and second repetitions; the MMN latency was increased in the
      second repetition. In the control group the MMN amplitude decreased on average by
      3.2 +/- 1.4 microV in the second trial, whereas in migraine patients it showed a
      slight increase of 0.21 +/- 0.11 microV in the second repetition. The MMN latency
      relieved in the second trial was significantly correlated with the duration of
      illness in the migraine patients (Spearman correlation coefficient: 0.69; P <
      0.05). The increases in N1 latency and MMN latency and amplitude, the latter
      correlated with duration of illness, seemed to be due to a reduced anticipatory
      effect of stimulus repetition in migraine patients. This suggests that such hypo
      activity of automatic cortical processes, subtending the discrimination of
      acoustic stimuli, may be a basic abnormality in migraine, developing in the
      course of the disease.

PMID- 15265056
TI  - Epidemiological and clinical characteristics with psychosocial aspects of tension
      type headache in Turkish college students.
AB  - We investigated the prevalence and clinical characteristics of tension-type
      headache (TTH), psychosocial factors contributing to the onset and aggravation of
      headache and coping mechanisms of individuals in a young population in Turkey.
      The sample consisted of 2226 university students, aged 7 to 21 years old. A self
      administered questionnaire inquiring about epidemiological and clinical features
      of headache was filled out by participants. TTH diagnosis was determined in
      accordance with the International Headache Society Criteria of 1988. The
      prevalence of TTH was 20.35% (25.54% for women and 14.25% for men). 43.7% of
      headache sufferers had one or more stressful life events before the onset of
      headache and stress was the most frequent aggravating factor of headache (52%).
      Resting (58.1%) was the most common coping style. In conclusion, TTH is not a
      rare condition in Turkish young people and psychosocial factors are always taken
      into consideration for diagnosis and treatment of TTH.

PMID- 15265057
TI  - Treatment of chronic tension-type headache with botulinum toxin: a double-blind,
      placebo-controlled clinical trial.
AB  - Botulinum toxin is increasingly advocated as effective treatment in chronic
      tension-type headache. We conducted a randomized, placebo-controlled clinical
      trial to prove efficacy of botulinum toxin in chronic tension-type headache.
      Patients were randomly assigned to receive botulinum toxin (maximum 100 units) or
      placebo (saline) in muscles with increased tenderness. After 12 weeks there was
      no significant difference between the two treatment groups in decrease of
      headache intensity on VAS (-3.5 mm, 95% confidence interval (CI) - 20 to +13),
      mean number of headache days (-7%; 95% CI - 20 to +4), headache hours per day (
      1.4%; 95% CI - 3.9 to +1.1), days on which symptomatic treatment was taken (
      1.9%; 95% CI - 11 to +7) and number of analgesics taken per day (-0.01; 95% CI 
      0.25-0.22). There was no significant difference in patient's assessment of
      improvement after week 4, 8 and 12. Botulinum toxin was not proven effective in
      treatment of chronic tension-type headache. Increased muscle tenderness might not
      be as important in pathophysiology of chronic tension-type headache as hitherto
      believed.

PMID- 15265058
TI  - Episodic hypnic headache?

PMID- 15265059
TI  - Migraine and depersonalization disorder.

PMID- 15265060
TI  - Meta-analysis of oral triptans.

PMID- 15265063
TI  - Biological therapies in the systemic management of psoriasis: International
      Consensus Conference.
AB  - Psoriasis is a chronic, immune-mediated disorder that usually requires long-term
      treatment for control. Approximately 25% of patients have moderate to severe
      disease and require phototherapy, systemic therapy or both. Despite the
      availability of numerous therapeutic options, the long-term management of
      psoriasis can be complicated by treatment-related limitations. With advances in
      molecular research and technology, several biological therapies are in various
      stages of development and approval for psoriasis. Biological therapies are
      designed to modulate key steps in the pathogenesis of psoriasis. Collectively,
      biologicals have been evaluated in thousands of patients with psoriasis and have
      demonstrated significant benefit with favourable safety and tolerability
      profiles. The limitations of current psoriasis therapies, the value of biological
      therapies for psoriasis, and guidance regarding the incorporation of biological
      therapies into clinical practice are discussed.

PMID- 15265065
TI  - Genetic diversity in German draught horse breeds compared with a group of
      primitive, riding and wild horses by means of microsatellite DNA markers.
AB  - We compared the genetic diversity and distance among six German draught horse
      breeds to wild (Przewalski's Horse), primitive (Icelandic Horse, Sorraia Horse,
      Exmoor Pony) or riding horse breeds (Hanoverian Warmblood, Arabian) by means of
      genotypic information from 30 microsatellite loci. The draught horse breeds
      included the South German Coldblood, Rhenish German Draught Horse, Mecklenburg
      Coldblood, Saxon Thuringa Coldblood, Black Forest Horse and Schleswig Draught
      Horse. Despite large differences in population sizes, the average observed
      heterozygosity (H(o)) differed little among the heavy horse breeds (0.64-0.71),
      but was considerably lower than in the Hanoverian Warmblood or Icelandic Horse
      population. The mean number of alleles (N(A)) decreased more markedly with
      declining population sizes of German draught horse breeds (5.2-6.3) but did not
      reach the values of Hanoverian Warmblood (N(A) = 6.7). The coefficient of
      differentiation among the heavy horse breeds showed 11.6% of the diversity
      between the heavy horse breeds, as opposed to 21.2% between the other horse
      populations. The differentiation test revealed highly significant genetic
      differences among all draught horse breeds except the Mecklenburg and Saxon
      Thuringa Coldbloods. The Schleswig Draught Horse was the most distinct draught
      horse breed. In conclusion, the study demonstrated a clear distinction among the
      German draught horse breeds and even among breeds with a very short history of
      divergence like Rhenish German Draught Horse and its East German subpopulations
      Mecklenburg and Saxon Thuringa Coldblood.

PMID- 15265066
TI  - B-F DNA sequence variability in Brazilian (blue-egg Caipira) chickens.
AB  - A total of 100 chickens from the Brazilian (blue-egg Caipira) native breed were
      studied in relation to exon 2 of the B-F genes of the major histocompatibility
      complex (MHC) region. After a first screening on 100 birds, 22 animals were
      selected for amplification, cloning and sequencing experiments of exons 2-4 (a
      total of 1048 bp) of their DNA. Twenty-three sequences were obtained, of which at
      least 10 appear novel. Inferred protein sequences were compared with those
      previously described, totalling 41 different sequences with amino acid changes in
      33 of the 88 sites in alpha1, and 34 of the 91 sites in alpha2 domains. Allele
      expression was investigated in these animals through cloning experiments. The
      blue-egg Caipira chickens may provide a source of novel B-F alleles for genetic
      improvement programmes.

PMID- 15265067
TI  - Microsatellite diversity, population subdivision and gene flow in the Lipizzan
      horse.
AB  - Blood samples of 561 Lipizzan horses from subpopulations (studs) of seven
      European countries representing a large fraction of the breed's population were
      used to examine the genetic diversity, population subdivision and gene flow in
      the breed. DNA analysis based on 18 microsatellite loci revealed that genetic
      diversity (observed heterozygosity = 0.663, gene diversity = 0.675 and the mean
      number of alleles = 7.056) in the Lipizzan horse is similar to other horse breeds
      as well as to other domestic animal species. The genetic differentiation between
      Lipizzan horses from different studs, although moderate, was apparent (pairwise
      F(ST) coefficients ranged from 0.021 to 0.080). Complementary findings explaining
      the genetic relationship among studs were revealed by genetic distance and
      principal component analysis. One genetic cluster consisted of the subpopulations
      of Austria, Italy and Slovenia, which represent the classical pool of Lipizzan
      horse breeding. A second cluster was formed by the Croatian, Hungarian and
      Slovakian subpopulations. The Romanian subpopulation formed a separate unit. The
      largest genetic differentiation was found between the Romanian and Italian
      subpopulation. Genetic results are consistent with the known breeding history of
      the Lipizzan horse. Correct stud assignment was obtained for 80.9% and 92.1% of
      Lipizzan horses depending on the inclusion or exclusion of migrant horses,
      respectively. The results of the present study will be useful for the development
      of breeding strategies, which consider classical horse breeding as well as recent
      achievements of population and conservation genetics.

PMID- 15265068
TI  - Impact of the ESR gene on litter size and production traits in Czech Large White
      pigs.
AB  - To evaluate the effect of the PvuII polymorphism of the oestrogen receptor gene
      on litter size and production traits in Czech Large White swine, data from 1250
      sows and 3600 litters were analysed with two four-trait animal models. The traits
      in the first model were number of piglets born alive in a sow's first litter,
      number of piglets born alive in second and subsequent litters, lifetime daily
      gain and lean meat percentage. The second model included number of piglets born,
      number of piglets born alive, number of piglets weaned and litter weight at
      weaning from first and subsequent litters. The oestrogen receptor (ESR) locus
      significantly affected prolicacy in the first parity and averaged over all
      parities (P < 0.05), with allele A superior to allele B. In the first parity, AA
      sows produced approximately 0.5 more live piglets per litter than BB sows.
      Averaged over all parities, this difference was c. 0.25 piglets. Results for
      total number of piglets born and number of piglets weaned were similar to results
      for numbers born alive. No significant dominance effect was found for prolificacy
      traits. For litter weight at weaning, no significant additive effect was observed
      at the ESR locus, but a significant negative dominance effect (-1.5 kg) was
      estimated averaged across parities (litters of AB sows were similar to litters of
      BB sows for this trait). No pleiotropic effect of the ESR polymorphism on average
      daily gain or lean meat percentage was found.

PMID- 15265069
TI  - Identification of an ovulation rate QTL in cattle on BTA14 using selective DNA
      pooling and interval mapping.
AB  - Increased twinning incidence in beef cattle has the potential to improve
      production efficiency. However, phenotypic selection for twinning rate is
      difficult because of the trait's low heritability and the long time interval
      necessary to collect phenotypic records. Therefore, this trait and the correlated
      trait of ovulation rate are ideal candidates for marker-assisted selection. The
      objective of this study was to complete a genome-wide search for ovulation rate
      quantitative trait loci (QTL) in two related sire families. The families
      (paternal halfsib sires 839802 and 839803) were from a population of cattle
      selected for ovulation rate at the USDA Meat Animal Research Center, Clay Center,
      Nebraska. Putative ovulation rate QTL have previously been identified in the
      839802 family on chromosomes 7 and 19; however, marker coverage in the original
      scan was not complete. This study fills the gaps in marker coverage of the
      earlier study by adding approximately 60 informative microsatellites to each sire
      family. Each family was genotyped using selective DNA pooling. Sons and daughters
      were included in either the high or low pool based on their estimated breeding
      value deviations from the mid-parent average (EBVMD) for ovulation rate.
      Approximately 40% (839802) and 26% (839803) of available progeny comprised the
      high and low pools combined. Pooled typing revealed possible associations
      (nominal P < 0.05) between ovulation rate and marker genotype for 11 and 15
      microsatellites in the 839802 and 839803 families, respectively. Subsequent
      interval mapping strengthened support for the presence of an ovulation rate QTL
      on BTA14 (chromosome-wise P < 0.02).

PMID- 15265070
TI  - Contributions of Portuguese cattle breeds to genetic diversity using marker
      estimated kinships.
AB  - The quantitative assessment of genetic diversity within and between populations
      is important for decision-making in genetic conservation plans. In our study, we
      applied the livestock core set method to define the contribution of 15 cattle
      breeds, 11 of which are Portuguese indigenous cattle breeds, to genetic
      diversity. In livestock core set theory genetic diversity is defined as the
      maximum genetic variance that can be obtained in a random-mating population that
      is bred from the populations present in that core set. Two methods to estimate
      marker-estimated kinships to obtain the contributions to the core set were used
      in this study: the weighted log-linear model (WLM) and the weighted log-linear
      mixed model (WLMM). The breeds that contributed most to diversity in the core set
      were Holstein-Friesian followed by the Portuguese Mertolenga and Cachena for both
      WLM and WLMM methods. The ranking of relative contributions of cattle breeds was
      maintained when we considered only the Portuguese cattle breeds. Furthermore, we
      were able to identify the marginal contributions and respective losses of
      diversity for each of the 11 Portuguese cattle breeds when we considered a subset
      of populations that are not threatened of being lost (the Safe set composed of
      the four exotic breeds present in this study). When WLM was used losses in
      genetic diversity ranged from 2.68 to 0.65% while the loss in founder genome
      equivalents ranged from 37.37 to 8.43% for Mertolenga and Brava de Lide breeds
      respectively. When WLMM was used losses in genetic diversity and founder genome
      equivalents were less extreme than for the WLM method, ranging from 1.27 to 0.69
      and 26.8 to 12.99 respectively.

PMID- 15265071
TI  - Molecular cloning, expression and functional characterization of the cytochrome
      P450 2A6 gene in pig liver.
AB  - Raising intact male pigs would have a significant economic impact on the pork
      industry because intact males have improved feed efficiency and a greater lean
      yield of the carcass compared with barrows. However, the presence of skatole, a
      major cause of boar taint, in meat from intact male pigs could be highly
      objectionable to consumers. It has been shown that CYP2A6 is a key enzyme in the
      hepatic metabolism of skatole and that the activity of CYP2A6 is negatively
      correlated with skatole accumulation in fat. The aim of this study was to isolate
      and characterize CYP2A6 from pig liver, as well as identify genetic polymorphisms
      in the CYP2A6 gene, and examine the association between these polymorphisms and
      skatole level. We identified a single base deletion in CYP2A6, resulting in a
      frame shift in the coding region that produces a non-functional enzyme, which was
      associated with high levels of skatole in fat tissue.

PMID- 15265072
TI  - Genomic characterization of a novel pair of ID genes in the rainbow trout
      (Oncorhynchus mykiss).
AB  - The ID (inhibitors of DNA binding/differentiation) proteins represent a family of
      dominant negative regulators of the basic helix-loop-helix transcription factors
      whose activities result in delayed cell differentiation and prolonged
      proliferation. A pair of expressed sequence tag clones with homologies to the ID
      proteins were identified and used to screen a rainbow trout bacterial artificial
      chromosome (BAC) library to identify clones containing homologues sequences.
      Phylogenetic analysis of the predicted amino acid sequences revealed close
      similarities to the rainbow trout ID1 protein, the genes were therefore
      classified as rainbow trout ID1B and ID1C. Genome characterization based on BAC
      sequencing showed each gene to have two exons separated by a small intron. The
      genes are 83% similar in their transcribed regions, yet they are only 64 and 65%
      similar in the upstream and downstream sequences, respectively. Using reverse
      transcription polymerase chain reaction, we found both genes to be expressed in a
      variety of tissues in the adult rainbow trout.

PMID- 15265064
TI  - An expanded comparative map of bovine chromosome 27 targeting dairy form QTL
      regions.
AB  - At present, the density of genes on the bovine maps is extremely limited and
      current resolution of the human-bovine comparative map is insufficient for
      selection of candidate genes controlling many economic traits of interest in
      dairy cattle. This study describes the chromosomal mapping of 10 selected gene
      associated markers to bovine linkage and radiation hybrid maps to improve the
      breakpoint resolution in the human-bovine comparative map near two previously
      identified quantitative trait loci for the linear type trait, dairy form. Two
      regions of conserved synteny not previously described are reported between the
      telomeric region of bovine chromosome 27 (BTA27) and human chromosome 3 (HSA3)
      p24 region and between the HSA4q34.1 region and BTA8. These data increase the
      number of genes positioned on the bovine gene maps, refine the human-bovine
      comparative map, and should improve the efficiency of candidate gene selection
      for the dairy form trait in cattle.

PMID- 15265073
TI  - Linkage arrangement of Na,K-ATPase genes in the tetraploid-derived genome of the
      rainbow trout (Oncorhynchus mykiss).
AB  - As part of our efforts to characterize Na,K-ATPase isoforms in salmonid fish, we
      investigated the linkage arrangement of genes coding for the alpha and beta
      subunits of the enzyme complex in the tetraploid-derived genome of the rainbow
      trout (Oncorhynchus mykiss). Genetic markers were developed from four of five
      previously characterized alpha-subunit isoforms (alpha1b, alpha1c, alpha2 and
      alpha3) and four expressed sequence tags derived from yet undescribed beta
      subunit isoforms (beta1a, beta1b, beta3a and beta3b). Sex-specific linkage
      analysis of polymorphic loci in a reference meiotic panel revealed that Na,K
      ATPase genes are generally dispersed throughout the rainbow trout genome. A
      notable exception was the colocalization of two alpha-subunit genes and one beta
      subunit gene on linkage group RT-12, which may thus share a conserved orthologous
      segment with linkage group 1 in zebrafish (Danio rerio). Consistent with
      previously reported homeologous relationships among the chromosomes of the
      rainbow trout, primers designed from the alpha3-isoform detected a pair of
      duplicated genes on linkage groups RT-27 and RT-31. Similarly, the evolutionary
      conservation of homeologous regions on linkage groups RT-12 and RT-16 was further
      supported by the map localization of gene duplicates for the beta1b isoform. The
      detection of homeologs within each gene family also raises the possibility that
      novel isoforms may be discovered as functional duplicates.

PMID- 15265074
TI  - Exclusion of galectin 9 as a candidate gene for hyperuricosuria in the Dalmatian
      dog.
AB  - All Dalmatian dogs have an inherited defect in purine metabolism leading to high
      levels of uric acid excretion in their urine (hyperuricosuria) rather than
      allantoin, the normal end product of purine metabolism in all other breeds of
      dog. Transplantation experiments have demonstrated that the defect is intrinsic
      to the liver and not the kidney. Uricase, the enzyme involved in the breakdown of
      urate into allantoin, has been shown to function in Dalmatian liver cells.
      Therefore, candidate genes for this defect include transporters of urate, a salt
      of uric acid, across cell membranes. We excluded one such urate transporter
      candidate, galectin 9, using a Dalmatian x Pointer backcross in which
      hyperuricosuria was segregating.

PMID- 15265075
TI  - Ovine alpha-amylase genes: isolation, linkage mapping and association analysis
      with milk traits.
AB  - On the basis of comparisons between cattle and sheep genome mapping information
      the ovine alpha-amylase gene was examined as a possible genetic marker for milk
      traits in sheep. The objective of the present study was to isolate, map and
      determine whether this gene is a candidate gene for milk traits. DNA fragments
      (832 and 2360 bp) corresponding to two different AMY genes were isolated, and one
      SNP in intron 3 and one GTG deletion in exon 3 of the 2360 bp DNA fragment were
      found. The 2360 bp ovine AMY DNA fragment was located on chromosome 1 by linkage
      mapping using the International Mapping Flock. No association was found between
      estimated breeding values for milk yield, protein and fat contents and AMY
      genotypes in a daughter design comprising 13 Manchega families with an average of
      29 daughters (12-62) per sire.

PMID- 15265076
TI  - The genes encoding bovine SP-A, SP-D, MBL-A, conglutinin, CL-43 and CL-46 form a
      distinct collectin locus on Bos taurus chromosome 28 (BTA28) at position q.1.8
      1.9.
AB  - Collectins are a group of C-type lectins involved in the innate immune system,
      where they mediate and modulate clearance of pathogens. The health status of
      cattle is of major economical and ethical concern; therefore, the study of bovine
      collectins is of importance. The collectins conglutinin, CL-43 and CL-46 are only
      present in Bovidae and the characterization of their genes indicates that they
      are structural descendants of another collectin, lung surfactant protein D (SP
      D). In this study, we assembled BAC clones into a contig spanning 330-1150 kb,
      which includes the bovine genes encoding the collectins SP-A (SFTPA), SP-D
      (SFTPD), mannan-binding lectin A (MBL1), CL-43 (COLEC9), CL-46 (COLEC13) and
      conglutinin (COLEC8). In the same contig, we also identified a gene that
      potentially encodes a novel conglutinin-like collectin (COLEC14). The arrangement
      of STFPA, SFTPD and MBL1 is homologous to the organization found in humans and
      mice, whereas the Bovidae-specific collectin genes, COLEC8, COLEC9 and COLEC13,
      extend from SFTPD. Proximal to the collectin locus at BTA28q1.8-1.9, and included
      in the contig, we found the microsatellite IDVGA8, which may be a valuable marker
      for tracking polymorphisms in the linked collectin genes.

PMID- 15265077
TI  - Comparative mapping of human chromosome 10 to pig chromosomes 10 and 14.
AB  - Identification of predictive markers in QTL regions that impact production traits
      in commercial populations of swine is dependent on construction of dense
      comparative maps with human and mouse genomes. Chromosomal painting in swine
      suggests that large genomic blocks are conserved between pig and human, while
      mapping of individual genes reveals that gene order can be quite divergent. High
      resolution comparative maps in regions affecting traits of interest are necessary
      for selection of positional candidate genes to evaluate nucleotide variation
      causing phenotypic differences. The objective of this study was to construct an
      ordered comparative map of human chromosome 10 and pig chromosomes 10 and 14. As
      a large portion of both pig chromosomes are represented by HSA10, genes at
      regularly spaced intervals along this chromosome were targeted for placement in
      the porcine genome. A total of 29 genes from human chromosome 10 were mapped to
      porcine chromosomes 10 (SSC10) and 14 (SSC14) averaging about 5 Mb distance of
      human DNA per marker. Eighteen genes were assigned by linkage in the MARC mapping
      population, five genes were physically assigned with the IMpRH mapping panel and
      seven genes were assigned on both maps. Seventeen genes from human 10p mapped to
      SSC10, and 12 genes from human 10q mapped to SSC14. Comparative maps of mammalian
      species indicate that chromosomal segments are conserved across several species
      and represent syntenic blocks with distinct breakpoints. Development of
      comparative maps containing several species should reveal conserved syntenic
      blocks that will allow us to better define QTL regions in livestock.

PMID- 15265078
TI  - A new single nucleotide polymorphism in the chicken pituitary-specific
      transcription factor (POU1F1) gene associated with growth rate.
AB  - The pituitary-specific transcription factor (POU1F1) is a protein which binds to
      and transactivates promoters of growth hormone (GH), prolactin (PRL) and thyroid
      stimulating hormone chain (TSHB)-encoding genes. Ten chicken populations (n =
      662), including six Chinese indigenous breeds, White Leghorn, paternal/maternal
      lines of brown egg layer and a paternal line of broiler, were used to detect
      single nucleotide polymorphisms in the pituitary-specific transcription factor
      gene (PIT1) by means of PCR-SSCP. A nucleotide transversion from adenine (A) to
      thymidine (T) at position 980 of the open reading frame of the PIT1 cDNA (GenBank
      accession no. AF029892) was identified. This nucleotide transversion results in
      an alteration of codon 299 from AAC to ATC, which leads to a change from
      asparagine (Asn) to isoleucine (Ile) in the POU domain of POU1F1. The
      distribution of allele and genotype frequencies differed significantly between
      meat-type chickens (higher frequencies of A and A/A) and layer-type chickens (P <
      0.01). Another experimental population with growth records was used to evaluate
      the relationship between this polymorphism and growth rate. The results revealed
      a positive relationship between genotype A/A and body weight at 8 weeks of age,
      indicating that the SNP in PIT1 gene is a potential molecular marker for early
      growth rate in chicken.

PMID- 15265079
TI  - Association of the heart fatty acid-binding protein (FABP3) gene with milk traits
      in Manchega breed sheep.
AB  - The ovine fatty acid-binding protein type 3 gene has been chosen as a functional
      candidate gene for milk traits. Two different single nucleotide polymorphisms
      (SNPs) of ovine FABP3 gene have been tested in a daughter design comprising 13
      families. No association was found between estimated breeding values for milk
      yield, protein and fat contents (FC) and genotypes across families using anova
      and transmission disequilibrium test (TDT). In within-family analysis, one family
      showed a significant effect for FC. These results could indicate linkage
      disequilibrium between the FABP3 gene and a quantitative trait loci (QTL) for FC,
      with the heterozygous genotype associated with a positive effect in this trait.

PMID- 15265080
TI  - The canine KRAS2 gene maps to chromosome 22.

PMID- 15265081
TI  - Genomic localization and SNP discovery in the bovine melanocortin receptor 4 gene
      (MC4R).

PMID- 15265082
TI  - Assignment of the porcine PLD2 gene to chromosome 12 and characterization of a
      SINE indel polymorphism.

PMID- 15265083
TI  - Sequencing and mapping of the porcine CCS gene.

PMID- 15265084
TI  - The protein kinase B, gamma (AKT3) gene maps to canine chromosome 7.

PMID- 15265085
TI  - The canine NRAS gene maps to CFA 17.

PMID- 15265086
TI  - Linkage mapping of chicken ovoinhibitor and ovomucoid genes to chromosome 13.

PMID- 15265087
TI  - Cloning and mapping of canine KIAA1753.

PMID- 15265088
TI  - Alcohol and homicide in Russia.

PMID- 15265089
TI  - Estimating substance abuse treatment need by state.

PMID- 15265090
TI  - Slow-release oral morphine versus methadone: a crossover comparison of patient
      outcomes and acceptability as maintenance pharmacotherapies for opioid
      dependence.
AB  - AIMS: To evaluate slow-release oral morphine (SROM) as an alternative maintenance
      pharmacotherapy to methadone for treatment of opioid dependence. DESIGN: Open
      label crossover study. SETTING: Out-patient methadone maintenance programme.
      PARTICIPANTS: Eighteen methadone maintenance patients. Intervention Participants
      were transferred from methadone to SROM (once-daily Kapanol trade mark ) for
      approximately 6 weeks before resuming methadone maintenance. MEASUREMENTS:
      Patient outcomes were assessed (1) during the transition between medications
      (dose requirements, withdrawal severity) and (2) after at least 4 weeks on a
      stable dose of each drug (treatment preference, patient ratings of treatment
      efficacy and acceptability, drug use, health, depression and sleep). FINDINGS:
      Transfer from methadone to SROM was associated with relatively mild withdrawal
      for the first 5 days; the final mean SROM : methadone dose ratio was 4.6 : 1.
      Compared to methadone, SROM was associated with improved social functioning,
      weight loss, fewer and less troublesome side-effects, greater drug liking,
      reduced heroin craving, an enhanced sense of feeling 'normal' and similar
      outcomes for unsanctioned drug use, depression and health. The majority of
      subjects preferred SROM (78%) over methadone (22%). CONCLUSIONS: These findings
      provide justification for further evaluation of SROM as a maintenance
      pharmacotherapy for opioid dependence.

PMID- 15265091
TI  - Mortality risk among new onset injection drug users.
AB  - AIMS: To characterize mortality experience among those who only recently started
      injection. DESIGN: Prospective study. SETTING: Independent study clinic within
      high drug use neighborhoods. PARTICIPANTS: In 1988-1989, we enrolled 256 adult
      injection drug users (IDUs) recruited through street outreach who had initiated
      injection within the prior 2 years. MEASUREMENTS: Consenting participants
      underwent venipuncture for HIV antibody testing and interviews. We prospectively
      ascertained date and cause of death through follow-up contact and registry
      linkages. Analyses included standardized mortality ratios (SMRs) with local,
      state and national mortality data, adjusted for age, gender and race. FINDINGS:
      Baseline median age was 30 years, 70% were male, 95% were African-American and
      90% injected within the prior 6 months. We identified 69 deaths through October
      2000; mortality rate was 3.3/100 person-years. The adjusted SMR with the USA (and
      Baltimore) as the reference for IDUs was 4.40 (2.43) for 1991-1992, which
      increased to 8.12 (4.13) by 1993-1994, decreased to 4.43 (2.13) by 1997-1998 and
      increased slightly to 5.35 (2.79) during 1999-2000. Excluding HIV-related
      mortality, SMRs remained elevated. Decline in SMRs was not linked to drug abuse
      treatment. CONCLUSIONS: These data demonstrate excess mortality among new-onset
      IDUs compared with demographically similar peers in the general population,
      indicating the need for interventions to prevent premature death among young
      IDUs.

PMID- 15265092
TI  - Characteristics of drug users who do or do not have care of their children.
AB  - AIMS: To compare the relative frequency of eight indicators of problem drug use
      and potentially adverse social circumstances in drug-using parents and non
      parents and to explore whether a profile based on these characteristics differs
      according to whether or not dependent children live with their drug-using parent.
      DESIGN: The study utilizes a 5 year national UK treatment monitoring system data
      set. SAMPLE: 61,425 users with, and 105,473 without dependent children accessing
      drug treatment services in England and Wales between January 1996 and December
      2000. MEASUREMENTS: Information about parenthood and children's residence was
      routinely collected. Drug use and social circumstance indicators were daily
      heroin use, daily alcohol use, regular stimulant use, sharing of injecting
      equipment, living with another user, living alone, unstable accommodation, and
      criminal justice referral. FINDINGS: There were clear differences between drug
      using parents according to where children live. Parents with children at home and
      non-parents showed fewer of the indicators than parents with children in care or
      elsewhere. Sixty-five percent of parents with none of the indicators lived with
      their children, compared with only 28% of those with three indicators and 9% of
      those with six or more indicators. Parents with children in care or living
      elsewhere showed the highest prevalence for each individual indicator.
      CONCLUSIONS: Drug-using parents demonstrate a range of potentially unfavourable
      drug use behaviours and social circumstances, but those whose children live with
      them use drugs less frequently and live in more favourable conditions than those
      whose children live elsewhere. Protective factors may operate in family
      situations, while severe drug use and adverse social circumstances may result in
      a breakdown of family structures.

PMID- 15265093
TI  - The effect of matching comprehensive services to patients' needs on drug use
      improvement in addiction treatment.
AB  - AIMS: To examine whether need-service matching in addiction treatment leads to
      improvements in drug use, and whether treatment duration mediates those
      improvements. DESIGN, PARTICIPANTS, MEASUREMENTS: This analysis utilizes
      prospective data from a US cohort of addiction treatment patients who reported
      service needs beyond core rehabilitative services (n = 3103). 'Drug use
      improvement' is the difference between the patient's peak drug use frequency (in
      days per month) in the year before intake and in the year after treatment.
      Overall and primary use of the major illicit drugs (heroin, powder or crack
      cocaine and marijuana) are considered separately. 'Need-service match' means that
      a patient rated a service as important at intake and reported its receipt during
      treatment. 'Percentage of needs matched' indicates the proportion of five service
      domains (medical, mental health, family, vocational and housing) so matched.
      FINDINGS: In mixed regression models controlling for multiple factors, a greater
      percentage of needs matched tended to improve primary (beta = 0.028, P = 0.09)
      and overall (beta = 0.049, P = 0.05) drug use in the follow-up year. Exclusion of
      treatment duration as a covariate doubled the magnitude of these coefficients.
      The benefits of matching were concentrated among the half of patients reporting
      needs in four to five rather than one to three domains, and were strongest among
      patients in long-term residential facilities. Addressing vocational and housing
      needs exerted the greatest effects. CONCLUSIONS: Matching comprehensive services
      to needs is a useful addiction treatment practice, especially for high-need
      patients. Treatment duration might partially mediate its effect.

PMID- 15265094
TI  - Intranasal cocaine use does not appear to be an independent risk factor for HCV
      infection.
AB  - AIMS: To determine the prevalence of HCV infection among intranasal cocaine users
      and evaluate underlying parental risk factors. DESIGN, SETTING AND PARTICIPANTS:
      A cross-sectional study evaluated prospectively 60 patients admitted to a
      chemical dependency unit. MEASUREMENTS: A standardized questionnaire was designed
      to obtain epidemiological data. Aminotransferases and anti-HCV antibodies were
      determined. Anti-HCV antibody positivity was confirmed by polymerase chain
      reaction (PCR). FINDINGS: Fifteen (25%) patients of 60 tested intranasal cocaine
      users were anti-HCV positive. Ten (75%) of them had detectable HCV-RNA.
      Comparison between 15 anti-HCV positive and 45 anti-HCV negative patients showed
      significant differences in mean age (35 versus 27 years), estimated time of drug
      use (10 versus 4 years), rate of elevated ALT and/or AST (60% versus 16%) and
      presence of parenteral risk factors (100% versus 7%). Comparison between patients
      with and without elevated aminotransferases showed significant difference in mean
      duration of drug use (8 versus 5 years) and rate of anti-HCV positivity (56%
      versus 14%). Among 15 anti-HCV positive patients, HCV-RNA was detectable in all
      with elevated aminotransferases and only one of six with normal aminotransferases
      (100% versus 17%). CONCLUSIONS: While there was a high prevalence of anti-HCV
      antibodies in this sample of intranasal cocaine users, the infection was highly
      correlated with the presence of intravenous (i.v.) drug use and duration of drug
      use. In this sample, therefore, intranasal cocaine use alone was not an important
      risk factor for HCV infection.

PMID- 15265095
TI  - A critical review of the causes of death among post-mortem toxicological
      investigations: analysis of 34 buprenorphine-associated and 35 methadone
      associated deaths.
AB  - AIMS: To assess the trends in the number, mortality and the nature of forensic
      cases involving toxicological detection of buprenorphine or methadone among
      toxicological investigations performed in Paris from June 1997 to June 2002.
      DESIGN: Retrospective, 5 year study with review of premortem data, autopsy,
      police reports, hospital data, and post-mortem toxicological analyses. SETTING
      AND PARTICIPANTS: 34 forensic cases of buprenorphine and 35 forensic cases of
      methadone detection among 1600 toxicological investigations performed at the
      Laboratory of Toxicology in the Medical Examiner's Office in Paris. MEASUREMENTS
      AND RESULTS: Therapeutic, toxic or lethal drug concentrations were defined based
      upon the results of blood analyses and the published literature. Drug
      concentrations were cross-referenced with other available ante- and post-mortem
      data. Subsequently, we classified a 'clear responsibility', 'possible
      responsibility' or 'not causative' role for buprenorphine or methadone in the
      death process, or 'no explanation of death'. Buprenorphine and methadone can be
      regarded as being directly implicated in, respectively, four of 34 death cases
      (12%) and three of 35 death cases (9%), and their participation in the lethal
      process is strongly plausible in eight (buprenorphine) and 11 (methadone)
      additional deaths. CONCLUSIONS: Analysis of causes of death reveals the
      difficulties in determining the role of substitution drugs in the death process,
      as many other factors may be involved, including circumstances surrounding death,
      past history, differential selection of subjects into either substitution
      modality and concomitant intake of other drugs (especially benzodiazepines and
      neuroleptics). The potential for synergistic or additive actions by other
      isolated molecules-particularly opioids, benzodiazepines, other psychotropes and
      alcohol-must be also considered.

PMID- 15265097
TI  - Substance abuse treatment needs and access in the USA: interstate variations.
AB  - AIMS: This study investigated interstate substance abuse treatment needs and
      access in the USA. DESIGN: After assessing the validity of recently developed
      survey and indicator measures, the study analysed the geographic distribution and
      nature of state substance abuse treatment needs. Substance abuse treatment
      utilization index scores were regressed on the need measurements to identify
      differences among state populations in treatment access. FINDINGS: The interstate
      substance abuse treatment need measures had evidence of reliability and construct
      validity. Treatment needs clustered in stable, distinct geographic patterns. The
      most severe problems, primarily reflecting alcoholism, were in the west. Drug and
      alcohol substance use disorders and related problems were not significantly
      correlated at this level of aggregation. There was evidence of regionalization of
      the drug-of-choice mix in treatment admissions. Only 21% of the variations in
      state treatment utilization rates stemmed from the prevalence of substance use
      disorders and related problems. The biggest treatment gaps were in the south and
      south-west, regions with large minority populations. CONCLUSIONS: Development of
      interstate survey and indicator measures of treatment needs has created new
      opportunities to broaden our understanding of substance abuse epidemiology and
      treatment access in the USA. The nature and severity of drug and alcohol problems
      vary from state to state, but the interstate disparities in treatment services
      remain even after variations in treatment need have been discounted. Further
      research is needed to understand the causes of these differences in treatment
      access.

PMID- 15265096
TI  - Prevalence of non-medical drug use and dependence among homosexually active men
      and women in the US population.
AB  - AIMS: The aim of this study was to compare patterns of drug use and dependence
      between homosexually experienced and exclusively heterosexually experienced
      individuals. DESIGN: We used a cross-sectional national household interview
      survey conducted in the United States. SETTING: Secondary data analysis of the
      1996 National Household Survey on Drug Abuse was employed. PARTICIPANTS:
      Participants were sexually active individuals, aged 18 years and older, who
      reported the genders of their sexual partners in the past 12 months; included 174
      homosexually experienced (98 men, 96 women) and 9714 exclusively heterosexually
      experienced (3922 men, 5792 women) respondents. MEASUREMENTS: Life-time, past 30
      days and daily use of nine classes of drugs. Symptoms of dysfunctional use and
      dependence. FINDINGS: There were consistent patterns of elevated drug use in
      homosexually experienced individuals for life-time drug use, but these were
      greatly attenuated for recent use. Homosexually experienced men were more likely
      to report use of marijuana, cocaine and heroin, and homosexually experienced
      women more likely to report use of marijuana and analgesics than individuals
      reporting only opposite-sex partners. Both homosexually active men and women were
      more likely than exclusively heterosexually active respondents to report at least
      one symptom indicating dysfunctional drug use across all drug classes, and to
      meet criteria for marijuana dependence syndrome. The only difference between
      homosexually experienced men and women was that men were more likely to report
      any daily drug use. CONCLUSIONS: These data are consistent with surveys
      suggesting that there is a moderate elevation of drug, particularly marijuana,
      use and dependence in gay and bisexual men and women when compared to
      heterosexual men and women.

PMID- 15265098
TI  - In 12-step groups, helping helps the helper.
AB  - AIMS: The helper therapy principle suggests that, within mutual-help groups,
      those who help others help themselves. The current study examines whether clients
      in treatment for alcohol and drug problems benefit from helping others, and how
      helping relates to 12-step involvement. DESIGN: Longitudinal treatment outcome.
      PARTICIPANTS: An ethnically diverse community sample of 279 alcohol- and/or drug
      dependent individuals (162 males, 117 females) was recruited through
      advertisement and treatment referral from Northern California Bay Area
      communities. PARTICIPANTS: were treated at one of four day-treatment programs.
      MEASUREMENTS: A helping checklist measured the amount of time participants spent,
      during treatment, helping others by sharing experiences, explaining how to get
      help and giving advice on housing and employment. Measures of 12-step involvement
      and substance use outcomes were administered at baseline and a 6 month follow-up.
      FINDINGS: Helping and 12-step involvement emerged as important and related
      predictors of treatment outcomes. In the general sample, total abstinence at
      follow-up was strongly and positively predicted by 12-step involvement at follow
      up, but not by helping during treatment; still, helping positively predicted
      subsequent 12-step involvement. Among individuals still drinking at follow-up,
      helping during treatment predicted a lower probability of binge drinking, whereas
      effects for 12-step involvement proved inconsistent. CONCLUSIONS: Findings
      support the helper therapy principle and clarify the process of 12-step
      affiliation.

PMID- 15265099
TI  - Under-reporting of alcohol consumption in household surveys: a comparison of
      quantity-frequency, graduated-frequency and recent recall.
AB  - AIM: To compare alternative survey methods for estimating (a) levels of at risk
      alcohol consumption and (b) total volume of alcohol consumed per capita in
      comparison with estimates from sales data and to investigate reasons for under
      reporting. SETTING: The homes of respondents who were eligible and willing to
      participate. PARTICIPANTS: A total of 21,674 Australians aged 14 years and older.
      DESIGN: A 2001 national household survey of drug use, experiences and attitudes
      with weights applied for age, sex, geographic location and day of week of
      interview. MEASURES: Self-completion questionnaire using quantity-frequency (QF)
      and graduated-frequency (GF) methods plus two questions about consumption
      'yesterday': one in standard drinks, another with empirically based estimates of
      drink size and strength. RESULTS: The highest estimate of age 14 + per capita
      consumption of 7.00 l of alcohol derived from recall of consumption 'yesterday'
      or 76.8% of the official estimate. The lowest was QF with 49.8%. When amount
      consumed 'yesterday' was recalled in standard drinks this estimate was 5.27 l. GF
      questions yielded higher estimates than did QF questions both for total volume
      (5.25 versus 4.54 l) and also for the proportion of the population at risk of
      long-term alcohol-related harm (10.6%versus 8.1%). With the detailed 'yesterday'
      method 61% of all consumption was on high risk drinking days. CONCLUSIONS:
      Questions about typical quantities of alcohol consumed can lead to
      underestimates, as do questions about drinking 'standard drinks' of alcohol.
      Recent recall methods encourage fuller reporting of volumes plus more accurate
      estimates of unrecorded consumption and the proportion of total alcohol
      consumption that places drinkers at risk of harm. However, they do not capture
      longer-term drinking patterns. It is recommended that both recent recall and
      measures of longer-term drinking patterns are included in national surveys.

PMID- 15265100
TI  - Weekend effects on binge drinking and homicide: the social connection between
      alcohol and violence in Russia.
AB  - AIMS AND DESIGN: This study employs unique newly available Russian mortality data
      to examine the social connection between binge drinking and homicide in the
      country. SETTING, PARTICIPANTS AND MEASUREMENTS: All death certificates of those
      aged 20-64 years in the Udmurt Republic, Russia, were analyzed according to day
      and cause of death for the years 1994-98. Deaths due to alcohol poisoning were
      used as a proxy for binge drinking. FINDINGS: There was a high bivariate
      correlation (r = 0.75) between the daily distribution of deaths due to alcohol
      and homicide. The number of alcohol deaths was significantly higher on Saturdays
      and Sundays (presumably as a result of drinking on Friday and Saturday nights)
      and the number of homicide deaths was significantly higher on Fridays and
      Saturdays. CONCLUSIONS: The levels of alcohol consumption and homicide in Russia
      are among the highest in the world, and there is mounting evidence that the two
      are related. Binge drinking, preference for distilled spirits and a high social
      tolerance for heavy drinking may act as social and cultural contextual factors
      that might increase the risk of violent outcomes. The high correspondence between
      the daily distribution of alcohol and homicide deaths provides indirect evidence
      for the social connection between them. While these findings do not represent a
      causal connection, when placed in the context of the growing literature on this
      topic they provide further support of an association between alcohol consumption
      and homicide rates in Russia and preliminary evidence for the intermediate role
      in this relationship played by social context.

PMID- 15265101
TI  - Do smokers know how to quit? Knowledge and perceived effectiveness of cessation
      assistance as predictors of cessation behaviour.
AB  - AIMS: Despite the existence of effective cessation methods, the vast majority of
      smokers attempt to quit on their own. To date, there is little evidence to
      explain the low adoption rates for effective forms of cessation assistance,
      including pharmaceutical aids. This study sought to assess smokers' awareness and
      perceived effectiveness of cessation methods and to examine the relationship of
      this knowledge to cessation behaviour. DESIGN: A random-digit-dial telephone
      survey (response rate = 76%) with 3-month follow-up was conducted with 616 adult
      daily smokers in South-Western Ontario, Canada. MEASUREMENTS: A baseline survey
      assessed smoking behaviour, as well as smokers' awareness and perceived
      effectiveness of cessation assistance. A follow-up survey measured changes in
      smoking behaviour and adoption of cessation assistance at 3 months. FINDINGS:
      Participants demonstrated a poor recall of cessation methods: 45% of participants
      did not recall nicotine gum, 33% did not recall the nicotine patch and 57% did
      not recall bupropion. Also, many participants did not believe that the following
      cessation methods would increase their likelihood of quitting: nicotine
      replacement therapies (36%), bupropion (35%), counselling from a health
      professional (66%) and group counselling/quit programmes (50%). In addition, 78%
      of smokers indicated that they were just as likely to quit on their own as they
      were with assistance. Most important, participants who perceived cessation
      methods to be effective at baseline, were more likely to intend to quit (OR =
      1.80, 95% CI: 1.12-2.90), make a quit attempt at follow-up (OR = 1.80, 95% CI:
      1.03-3.16) and to adopt cessation assistance when doing so (OR = 3.62, 95% CI:
      1.04-12.58). CONCLUSIONS: This research suggests that many smokers may be unaware
      of effective cessation methods and most underestimate their benefit. Further,
      this lack of knowledge may represent a significant barrier to treatment adoption.

PMID- 15265102
TI  - Inattentiveness, parental smoking and adolescent smoking initiation.
AB  - AIMS: To examine how adolescents' inattentive behaviour, together with parental
      smoking patterns, predicts smoking initiation by age 14. DESIGN, SETTINGS: A
      prospective, longitudinal study: baseline at ages 11-12, follow-up at age 14. A
      population-based sample of Finnish twins, born 1983-1987, with parents and
      classroom teachers as additional informants. Two groups were formed, allocating
      the co-twins of each family into separate groups: the study sample and a
      replication sample. PARTICIPANTS: Twin individuals (n = 4552), aged 11-12 at
      baseline and 14 (average 14.04 years) at follow-up. MEASUREMENTS: At baseline,
      inattentiveness was assessed with the Multidimensional Peer Nomination Inventory
      (MPNI, Teacher Form) and parental smoking with individual questionnaires
      completed by each twins' parents; at the age 14 follow-up, adolescent smoking was
      assessed with a self-report questionnaire. FINDINGS: At age 14, 57% reported
      never having smoked, 34% had experimented with cigarettes and 9% were current
      smokers. Inattentiveness and parental smoking additively predicted both
      experimental and current smoking in adolescence. The effects were independent of
      each other. CONCLUSIONS: The risk related to inattentiveness itself is high, but
      in combination with the effects of parental smoking, the probability of current
      smoking can rise as high as 38%, compared with 5% without these two risk factors.
      For prevention purposes, parental commitment to non-smoking should be emphasized.

PMID- 15265103
TI  - Behavioral autarcesis-reprise.

PMID- 15265104
TI  - Footnotes to Hall (2004).

PMID- 15265105
TI  - Highly active antiretroviral therapy among HIV-infected people with alcohol and
      substance misuse problems: the impact of substance abuse treatment.

PMID- 15265107
TI  - Amazing good news.

PMID- 15265113
TI  - Transfusion Medicine Illustrated: Donath-Landsteiner antibody-associated
      hemolytic anemia after Haemophilus influenzae infection in a child.

PMID- 15265114
TI  - Things are seldom what they seem: Skim milk masquerades as cream--a platelet
      saga.

PMID- 15265115
TI  - Platelet transfusion and cardiac surgery: a cautionary tale.

PMID- 15265116
TI  - Methods for the analysis of bleeding outcomes in randomized trials of PLT
      transfusion triggers.
AB  - BACKGROUND: A number of methodologic challenges arise in the analysis of bleeding
      data from clinical trials of PLT transfusion triggers. It is important to
      understand the assumptions and role of the various methods of analysis to
      interpret published trials and to design future studies appropriately. STUDY
      DESIGN AND METHODS: The methods of analysis used for testing the effectiveness
      and safety of transfusion strategies are reviewed from several recent PLT
      transfusion trigger trials. The underlying assumptions of these methods are
      discussed, as well as the clinical interpretations of the resulting summary
      statistics. Four methods of analysis were applied to data from a large PLT
      transfusion trigger study to illustrate the differences in the interpretations
      that can arise from various approaches. RESULTS: PLT transfusion trigger trials
      of patients with leukemia have based their primary analyses on 1) simple
      dichotomous classifications of whether or not at least 1 day of clinically
      important bleeding was experienced; 2) the time to the first day of clinically
      important bleeding; and 3) the proportion of days at risk with clinically
      important bleeding. Recurrent event methods provide a robust alternative approach
      to the analysis of this kind of data and should be considered if interest is in
      capturing the overall burden of bleeding over time. These four methods differ in
      the extent to which they utilize information on the number of days with bleeding
      and the temporal variation in bleeding patterns. Inferences drawn regarding the
      relative safety and efficacy of different transfusion triggers can vary depending
      on the method of analysis. CONCLUSION: To rigorously design and analyze future
      PLT transfusion studies based on bleeding outcomes, it is important to have a
      clear understanding of the interpretation of the different ways of analyzing
      bleeding outcomes. The analysis strategy should be selected based on the clinical
      question being addressed.

PMID- 15265117
TI  - Platelet transfusions during coronary artery bypass graft surgery are associated
      with serious adverse outcomes.
AB  - BACKGROUND: Platelet (PLT) transfusions are administered in cardiac surgery to
      prevent or treat bleeding, despite appreciation of the risks of blood component
      transfusion. The current analysis investigates the hypothesis that PLT
      transfusion is associated with adverse outcomes associated with coronary artery
      bypass graft surgery (CABG). STUDY DESIGN AND METHODS: Data originally collected
      during double-blind placebo-controlled phase III trials for licensure of Trasylol
      (aprotinin injection) were retrospectively analyzed. Adverse outcome data of
      patients (n = 1720) that received, and did not receive, perioperative PLT
      transfusion were compared. Logistic regression analysis was used to assess the
      association of perioperative adverse events with PLT transfusion. Propensity
      scoring analysis was used to verify results of the logistic regression. RESULTS:
      Patients receiving PLTs were more likely to have prolonged hospital stays, longer
      surgeries, more bleeding, re-operation for bleeding, and more RBC transfusions,
      and less likely to have full-dose aprotinin administration. Adverse events were
      statistically more frequent in patients that received one or more PLT
      transfusion. Logistic regression analysis showed that PLT transfusion was
      associated with infection, vasopressor use, respiratory medication use, stroke,
      and death. Propensity scoring analysis confirmed the risk of PLT transfusion.
      CONCLUSIONS: PLT transfusion in the perioperative period of CABG was associated
      with increased risk for serious adverse events. PLT transfusion may be a
      surrogate marker for sicker patients and have no causal role in the outcomes
      observed. However, a direct contribution to outcomes remains possible.

PMID- 15265118
TI  - Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura
      hemolytic uremic syndrome.
AB  - BACKGROUND: Recurrent thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome (TTP-HUS) during a subsequent pregnancy is an important concern because
      pregnancy may increase the risk for relapse. STUDY DESIGN AND METHODS: Outcomes
      of all pregnancies after recovery from TTP-HUS in the Oklahoma TTP-HUS Registry,
      a cohort of 301 consecutive patients during the period of 1989 through 2003, were
      assessed and compared to the total published experience. RESULTS: In the Oklahoma
      Registry, 3 of 7 (43%) women with idiopathic TTP-HUS, 2 of 11 (18%) women who
      were pregnant/postpartum, and 0 of 1 (0%) woman with a bloody diarrhea prodrome
      at their initial presentation were diagnosed with TTP-HUS during a subsequent
      pregnancy; all 5 women recovered. In published reports, 10 of 11 (91%) women with
      idiopathic TTP-HUS and 11 of 18 (61%) women who were pregnant/postpartum at their
      initial presentation, and all 11 (100%) women with congenital TTP-HUS were
      diagnosed with TTP-HUS during a subsequent pregnancy. Rates of recurrence in the
      Oklahoma Registry may be less because of case report bias for exceptional
      patients. Recurrent TTP-HUS was difficult to diagnose because other pregnancy
      related complications were frequent. CONCLUSIONS: Although pregnancies in these
      women were often complicated, a future pregnancy may be a safe and appropriate
      decision for women who have recovered from TTP-HUS.

PMID- 15265119
TI  - Photochemical treatment of platelet concentrates with amotosalen hydrochloride
      and ultraviolet A light inactivates free and latent cytomegalovirus in a murine
      transfusion model.
AB  - BACKGROUND: A photochemical treatment (PCT) process utilizing amotosalen
      hydrochloride and long wavelength UVA light has been developed to inactivate
      pathogens in PLTs. This study investigated the effects of amotosalen/UVA
      treatment on free and latent murine CMV (MCMV) in PLT preparations using a murine
      model of transfusion-transmitted CMV (TT-CMV). STUDY DESIGN AND METHODS: In a
      model of latent MCMV infection, "donor" mice received 1 x 10(6) plaque-forming
      units (PFUs) MCMV and were rested 14 days. Subsequently harvested, pooled, and
      washed WBCs were PCR positive for MCMV. Murine WBC doses of 1 x 10(4), 1 x 10(5),
      and 1 x 10(6) were added to human apheresis PLTs in 35 percent autologous plasma
      and 65 percent PLT AS (PAS). The WBC-PLT products were treated with 150 micro
      mol/L amotosalen and 0.6 J per cm2 UVA and transfused via tail vein injection
      into recipient mice. Recipients were killed on Day 14. Blood and spleens were
      collected and assayed for MCMV by PCR. In a parallel model of active infection
      with free virus, human PLT in 35 percent autologous plasma and 65 percent PAS
      were dosed with 1 x 10(5) and 1 x 10(6) PFUs of MCMV. All other procedures were
      as described above. RESULTS: In the absence of amotosalen/UVA-pretreatment,
      transfusion of PLT latently or actively infected with MCMV produced TT-CMV in a
      dose-dependent fashion. In contrast, all transfusion recipients of identical PLT
      preparations pretreated with amotosalen/UVA were uniformly PCR negative for MCMV
      (abrogation of TT-CMV; p < 0.05). CONCLUSIONS: PCT of PLT preparations with the
      specified doses of amotosalen hydrochloride and UVA light prevents transfusion
      transmission of free and latent MCMV in a murine model. These results suggest
      that PCT of human PLTs with amotosalen/UVA should also effectively abrogate TT
      CMV in the clinical setting.

PMID- 15265120
TI  - Detection of bacterial contamination of platelet components: six years'
      experience with the BacT/ALERT system.
AB  - BACKGROUND: Hemovigilance has shown that bacteria cause more fatalities than
      other infections together. Surveillance for detection of bacteria in platelets
      (PLTs) was initiated. Concomitantly, the storage period for PLTs was extended
      from 5 to 7 days to reduce cost. STUDY DESIGN AND METHODS: Analysis was performed
      of all cases of a positive signal in a screening procedure for contaminated PLTs
      taking into account results of confirmative cultures and results of culture from
      blood components including bacteria strains. Records were assessed from patients
      transfused with blood components issued before the screening culture became
      positive. RESULTS: Samples were collected from 22,057 PLT units. An initial
      reaction was seen in 84 (0.38%). Growth was confirmed in 70 of these. Of the
      associated PLT units, 26 had been issued or outdated at the time when the culture
      was found to be reactive, in 27 bacteria were found, and in 17 cultures were
      negative. The bacteria found were mainly from normal skin flora. Sixty-six
      patients received 75 blood components issued before the screening system alarmed.
      None of these patients had a transfusion reaction reported. The outdating fell to
      less than 5 percent. CONCLUSION: A screening system for detection of bacterial
      contamination was implemented without increase in cost owing to extension of
      storage time to 7 days. Transfusion of several contaminated blood components was
      prevented.

PMID- 15265121
TI  - Validation of BacT/ALERT plastic culture bottles for use in testing of whole
      blood-derived leukoreduced platelet-rich-plasma-derived platelets.
AB  - BACKGROUND: Bacterial detection of platelet (PLT)-rich-plasma (PRP)-derived PLTs
      presents unique challenges for countries that do not allow pooling before
      storage. This study validated the BacT/ALERT for use in testing pooled PRP
      derived PLTs with nine contaminating organisms. STUDY DESIGN AND METHODS:
      Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella
      pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia
      marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated
      into two PRP-derived PLT pools (target, 10 and 100 colony-forming units
      [CFUs]/mL; actual recovered concentrations, 5 and 90 CFUs/mL). Four milliliters
      of each postbacterial inoculation sample was inoculated into both plastic aerobic
      and anaerobic bottles and 0.5 mL was plated onto blood agar. RESULTS: All
      organisms (excluding P. acnes) were detected in 8.2 to 22.0 and 7.6 to 20.3 hours
      (10 and 100 CFUs/mL, respectively) and the mean time to detection was 15.0 and
      13.1 hours (10 and 100 CFUs/mL, respective). P. acnes was detected with the
      anaerobic bottles in a mean of 74.9 and 64.3 hours (10 and 100 CFUs/mL,
      respectively). With E. cloacae, E. coli, K. pneumoniae, S. marcescens, and S.
      viridans detection with the anaerobic bottles was faster or equivalent to the
      detection with the aerobic bottles. This was most notable with S. viridans where
      the anaerobic bottle was reactive on average 21.6 and 10.8 hours (10 and 100
      CFUs/mL, respectively) faster than the aerobic bottle. CONCLUSIONS: This study
      validates the use of the BacT/ALERT system for the detection of bacteria in PRP
      derived PLTs in a pooled format. Overall, the use of the BacT/ALERT system
      allowed the detection of pooled PRP-derived PLTs inoculated with nine bacteria at
      10 and 100 CFUs per mL in 7.6 to 22.0 hours (excluding P. acnes).

PMID- 15265122
TI  - Human parvovirus B19 in young male patients with hemophilia A: associations with
      treatment product exposure and joint range-of-motion limitation.
AB  - BACKGROUND: To evaluate the risk of human parvovirus B19 (B19) transmission in
      recombinant antihemophilic factor, the seroprevalence among 798 two- to seven
      year-old boys with hemophilia was compared. Also, data collected on joints were
      used to assess relations between B19 serostatus and joint range-of-motion (ROM)
      limitation. STUDY DESIGN AND METHODS: Staff at US hemophilia treatment centers
      collected data on product exposures and ROM of 10 joints and provided blood
      specimens as part of blood safety surveillance. Blood was tested for
      immunoglobulin G anti-B19. Associations between B19 seropositivity and treatment
      products and joint ROM limitations were examined in multivariate analyses.
      RESULTS: Compared to children who received no product, the odds of B19
      seropositivity were 0.8 (p = 0.5), 1.9 (p = 0.05), and 7.6 (p < 0.001) for those
      children who received recombinant antihemophilic factor only, both recombinant
      antihemophilic factor and plasma-derived factor, and plasma-derived factor only,
      respectively. Children who were anti-B19 positive had an average 8 degrees less
      overall ROM (p = 0.002) than those who were B19 antibody negative after
      adjustment for other risk factors. CONCLUSION: The risk of B19 transmission by
      recombinant antihemophilic factor is low. Previous B19 infection is associated
      with ROM limitations in very young male patients with hemophilia. Virus
      inactivation techniques effective against B19 and other nonenveloped viruses are
      needed.

PMID- 15265123
TI  - Positively charged porphyrins: a new series of photosensitizers for sterilization
      of RBCs.
AB  - BACKGROUND: Photodynamic treatment could be a way to inactivate pathogens in
      RBCs. The objective of this study was to characterize the virucidal activity and
      RBC-damaging activity of a series of cationic porphyrins. Using the most
      efficacious photosensitizer, various in-vitro human RBC quality variables and in
      vivo RBC survival in Rhesus monkeys were evaluated. STUDY DESIGN AND METHODS:
      RBCs, spiked with 5 log of extracellular VSV, were treated with porphyrins (25
      micro mol/L) and red light (100 W/m2) and essayed for virucidal activity. In
      vitro RBC quality variables were assessed during 5 weeks of storage in various
      ASs. In-vivo survival was investigated with autologous RBCs in Rhesus monkeys.
      RESULTS: Tri-P(4) was by far the best sensitizer of a series tested, giving the
      least hemolysis under conditions that resulted in 5 log-kill of extracellular
      VSV. Under our experimental conditions, the percentage hemolysis in treated cells
      was 5.1 +/- 1.1 percent after 5 weeks of storage in SAG-M compared to 1.9 +/- 1.1
      percent in the untreated control. Storage in AS-3 resulted hemolysis of 2.3 +/-
      1.9 percent. With the exception of IgG binding and potassium leakage, RBC quality
      variables remained unchanged after photodynamic treatment. Addition of reduced
      glutathione (GSH) during treatment reduced IgG binding. The 24-hour recovery and
      T50 of treated RBCs in Rhesus monkeys were satisfactory. CONCLUSION: Porphyrin
      Tri-P(4) may be a suitable photosensitizer for sterilization of RBCs. However,
      further exploration to optimize the method is necessary to reach clinically
      acceptable goals.

PMID- 15265124
TI  - Multicenter evaluation of a whole-blood filter that saves platelets.
AB  - BACKGROUND: Whole-blood (WB) leukoreduction filters in current use retain the
      majority of PLTs. A new whole-blood filter, which retains significantly fewer of
      the PLTs (or saves PLTs [WB-SP]), has been developed. The performance
      characteristics of the WB-SP filter have been evaluated in a multicenter study.
      STUDY DESIGN AND METHODS: A total of 617 units of WB was collected into quadruple
      bag sets with an integrated WB-SP filter, leukoreduced, and processed into
      leukoreduced RBCs (LR-RBC), plasma (LR-PL), and buffy coats (LR-BC) from which,
      pooled, leukoreduced, PLT concentrates (LR-PCs) were produced. Recovery, yield,
      and residual WBCs were assessed in prepared blood components. RESULTS: The median
      residual WBC number in the LR-RBCs was 0.05 x 10(6) (range, <0.05-3.8), exceeding
      1 x 10(6) in 0.6 percent of the units. Median Hb content in LR-RBC was 50 g
      (range, 34-72), reflecting a final RBC recovery of 81 +/- 6 percent. The median
      WBC content of the LR-PC was 0.05 x 10(6) (range, <0.05-0.28), with none
      exceeding 1 x 10(6). The median PLT content of the LR-PC, per individual
      donation, was 6.4 x 10(10) (range, 4.1-10.7), representing a final recovery of 62
      +/- 10 percent. The mean FVIII activity was 104 +/- 25 percent and 83 +/- 11
      percent in plasma separated from fresh or overnight stored WB, respectively.
      CONCLUSION: Use of the WB-SP filter makes it possible to obtain three
      leukoreduced blood components with only one filtration step. The WB-SP filter
      showed good leukoreduction performance and recovery of all blood components
      including PLTs.

PMID- 15265125
TI  - Storage of platelets in additive solution for up to 12 days with maintenance of
      good in-vitro quality.
AB  - BACKGROUND: Storage of PLT concentrates (PCs) may be extended beyond 5 days,
      provided in-vitro and in-vivo variables allow longer storage and bacterial
      screening is performed. The aim of this study was to examine in-vitro storage
      characteristics of PCs in various storage solutions: plasma only, or mixtures of
      plasma with PAS-II, PAS-III, PAS-IIIM, and Composol. STUDY DESIGN AND METHODS:
      PCs from five pooled buffy-coats and WBCs reduced by filtration were stored in
      1.3-L butyryl-tri-hexyl-citrate-plasticised PVC containers. First, a paired
      comparison was made between PAS-II and Composol, with 35-percent final plasma
      concentration (n = 10). Then, plasma, PAS-III with 30-percent plasma, PAS-IIIM
      with 20- and 30-percent plasma, and Composol with 20 and 30-percent final plasma
      concentration were compared (n = 5 pairs). Finally, 50 PCs in Composol with 35
      percent final plasma concentration were studied. RESULTS: PCs in PAS-II or
      Composol had a mean +/- SD pH of 6.95 +/- 0.09 and 6.96 +/- 0.08 at Day 12,
      respectively. For PCs in PAS-IIIM and Composol with 30-percent final plasma
      concentration, pH on Day 7 was 7.00 +/- 0.02 and 6.83 +/- 0.05. With 20-percent
      final plasma concentration, pH was 6.98 +/- 0.02 and 6.81 +/- 0.03 for PAS-IIIM
      and Composol, respectively. PCs in PAS-III with 30-percent plasma had a pH on Day
      7 of 6.87 +/- 0.03, whereas PCs in 100-percent plasma had a pH of 7.05 +/- 0.03.
      PCs in Composol with 35-percent plasma maintained pH greater than 6.8 in 48 of 50
      of the units (96%), averaging 7.00 +/- 0.10 on Day 8. CONCLUSION: In-vitro
      quality of PCs in AS with at least 35-percent plasma can be maintained for 7 to
      12 days after collection.

PMID- 15265126
TI  - Prestorage pooled whole-blood-derived leukoreduced platelets stored for seven
      days, preserve acceptable quality and do not show evidence of a mixed lymphocyte
      reaction.
AB  - BACKGROUND: Prestorage pooling of whole-blood-derived PCs (WBD-PCs) would be
      advantageous to transfusion services in that it would make the product available
      in a more timely manner, reduce wastage of untransfused pools, and simplify
      bacterial screening by allowing testing of the pool rather than each single PLT
      concentrate (PC). STUDY DESIGN AND METHODS: Four to six individual leukoreduced
      PCs were pooled into a 1.5-L CLX-HP PLT storage bag using a sterile connecting
      device. Controls were individual prestorage leukoreduced PCs that were stored as
      single products. Products were sampled on Days 5 and 7 for measures of PLT
      quality; coagulation, fibrinolytic and complement activation; and for evidence of
      a mixed lymphocyte reaction. RESULTS: The pH level was well maintained to Day 7
      with no prestorage pool having a pH below 6.7. Day 7 studies showed no evidence
      of coagulation or difference in complement activation. F1.2 levels did not differ
      between Days 5 and 7, but a 10- to 15-percent increase in C3a des-Arg was
      observed between these days in all product types. Day 7 activated lymphocyte
      surface markers (CD69, CD71, HLA-DR) were all at lower limits of detection in the
      prestorage pooled products, and levels of supernatant cytokines were either not
      different between product types on either study day or, if different, were lower
      in the prestorage pooled products. CONCLUSION: There is no evidence of a
      deterioration in quality, activation of coagulation or complement, or a mixed
      lymphocyte reaction attributable to the prestorage pooling process with up to 7
      days of storage.

PMID- 15265127
TI  - Human platelet antigen-specific alloantibodies implicated in 1162 cases of
      neonatal alloimmune thrombocytopenia.
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NATP) caused by fetomaternal
      mismatch for human platelet (PLT) alloantigens (HPAs) complicates approximately 1
      in 1000 to 1 in 2000 pregnancies and can lead to a serious bleeding diathesis,
      intracranial hemorrhage, and sometimes death of the fetus or neonate. As a
      national reference center for NATP investigations, our experience with this
      entity over a 12-year period was reviewed. STUDY DESIGN AND METHODS: The
      laboratory records of all cases of suspected NATP referred for evaluation from
      January 1, 1990, to December 31, 2002, were analyzed. The spectrum of PLT
      alloantibody specificities identified was compared with an earlier reported
      series of serologically verified NATP cases. RESULTS: HPA-specific alloantibodies
      were identified in 1162 (31%) of 3743 sera of mothers of infants with clinically
      suspected NATP. Maternal HPA-1a (PlA1) alloimmunization accounted for the
      majority (79%) of confirmed NATP cases, with HPA-5b (Bra), HPA-3a (Baka), and HPA
      1b (PLA2) alloantibodies accounting for 9, 2, and 4 percent of cases,
      respectively. In addition, an increase in the number of cases in which multiple
      HPA-specific alloantibodies were present in maternal sera was observed during the
      study period. CONCLUSION: Although, as with the earlier series, maternal HPA-1a
      alloimmunization was the dominant cause of NATP, the identification of an
      increasing number of cases due to alternative HPA polymorphisms suggests that
      investigation for HPA-1 incompatibility alone is no longer sufficient to fully
      evaluate clinically suspect NATP cases.

PMID- 15265128
TI  - Diclofenac-induced antibodies against red blood cells are heterogeneous and
      recognize different epitopes.
AB  - BACKGROUND: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug
      implicated as a cause of immune hemolytic anemia. Drug derivatives have been
      suggested to be an important-or probably the primary-immunizing agent in drug
      induced immune reactions. A systematic evaluation of 12 patients with DCF-induced
      immune hemolysis is reported. STUDY DESIGN AND METHODS: All sera samples were
      evaluated with standard serologic tests for the detection of red blood cells
      (RBCs) and platelet (PLT) antibodies in the presence of DCF, DCF-urine (DCF-U),
      and five chemically defined metabolites. RESULTS: Twelve patients' sera samples
      reacted with DCF-U, but only 9 reacted with DCF. When derivatives were tested, no
      metabolite was recognized by all sera samples (although 4'-OH-DCF was recognized
      by 11/12), and no metabolite remained unrecognized. As demonstrated with Rh(null)
      cells, the Rh complex may represent an important, but not the only, target
      protein for which drug-dependent antibodies are specific. PLT-reactive antibodies
      were not detectable. CONCLUSION: There is evidence that patients with DCF-induced
      immune hemolysis produce a broad spectrum of anti-DCF/RBC antibodies. 4'-OH-DCF
      seems to represent the most immunogenic metabolite. Nevertheless, all patients'
      sera samples contain a mixture of antibodies that recognize several and
      distinguishable epitopes. These epitopes consist of different drug metabolites
      and a target protein on the RBC surface, which appears to be the Rh complex in
      many, but not in all, cases. Additional target proteins remain to be identified.

PMID- 15265129
TI  - Decreased deformability of donor red blood cells after intrauterine transfusion
      in the human fetus: possible reason for their reduced life span?
AB  - BACKGROUND: The life span of donor red blood cells (RBCs) is reduced in the fetus
      with Rh hemolytic disease. This may have resulted from donor or recipient
      factors. STUDY DESIGN AND METHODS: Studied in vitro was the effect of gamma
      irradiation on hemolysis, methemo-globin (metHb), and lipid peroxidation of donor
      RBCs and the ability of fetal and adult plasma to protect irradiated RBCs from
      induced lipid peroxidation. Also studied in vivo were the effects after the time
      that donor RBCs reside in the fetus by measuring its lipid peroxidation,
      cholesterol-to-phospholipid ratios, and deformability of RBCs. RESULTS:
      Irradiation barely increased hemolysis and metHb formation and did not increase
      lipid peroxidation. Plasma samples of D+ fetuses inhibited induced oxidative
      stress less than plasma samples of adults. Nevertheless, in vivo lipid
      peroxidation of the donor RBC membrane had not increased, whereas the molar
      cholesterol-to-phospholipid ratio increased from 1.08 +/- 0.11 to 1.38 +/- 0.12.
      It became identical to that of the fetal RBCs (1.44 +/- 0.12). Before
      transfusion, the deformability of the adult RBCs (elongation index, 0.578 +/-
      0.013) was better than that of the fetal cells (elongation index, 0.494 +/-
      0.027), but decreased to fetal levels after transfusion (elongation index, 0.518
      +/- 0.039). CONCLUSION: Irradiation of the RBCs and a reduced fetal antioxidant
      capacity do not lead to in vivo lipid peroxidation. The shorter life span of
      donor cells in the fetus probably results from a decreased deformability of the
      RBCs after transfusion, most likely owing to an increased cholesterol-to
      phospholipid ratio.

PMID- 15265130
TI  - Validation and assessment of a blood-donor arm disinfectant containing
      chlorhexidine and alcohol.
AB  - BACKGROUND: To minimize the bacterial contamination rate in blood collected from
      donors, a study was designed to evaluate the suitability of a single-use
      chlorhexidine-alcohol antiseptic for donor arm preparation at all blood
      collection venues in Australia. STUDY DESIGN AND METHODS: A prospective study of
      bacterial load on the skin was performed on 616 blood donors' arms before and
      after disinfection using a direct swabbing and plating technique. Disinfection
      was achieved with a swab containing 1 percent chlorhexidine gluconate with 75
      percent alcohol, which was applied to the skin in a prescribed method. Feedback
      from blood donors and staff was obtained using questionnaires. RESULTS: After
      disinfection, 99 percent of donor arms had bacterial counts of 5 cfu per plate or
      less, and 99.5 percent had counts of 10 cfu per plate or less, respectively. The
      mean colony count for all donors after disinfection was 0.39, and the percentage
      reduction was 99 compared to predisinfection. Sixteen donors (3%) noted transient
      skin irritation. The majority of staff (64%) preferred not to use the new
      disinfectant due to the difficulty opening the packaging and an excessive amount
      of antiseptic solution per pack. CONCLUSION: The bacteriologic study showed that
      the disinfectant satisfied the requirements of the Australian Red Cross Blood
      Service for use to prepare blood-donor arms before venesection. An improvement to
      the packaging was required before it could be acceptable to all staff.

PMID- 15265131
TI  - Comparison of demographic and donation profiles and transfusion-transmissible
      disease markers and risk rates in previously transfused and nontransfused blood
      donors.
AB  - BACKGROUND: Increasing concern about transfusion transmission of variant
      Creutzfeldt-Jakob disease has resulted in indefinite deferral of transfused
      donors in France and the UK. Little is known, however, about the impact of
      indefinite deferral of transfused donors on blood safety and availability in the
      US. STUDY DESIGN AND METHODS: Data were collected on allogeneic donations at five
      US blood centers during 1991 through 2000. Donation characteristics, prevalence,
      and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and
      hepatitis C virus (HCV) were compared between transfused and nontransfused
      donors. Unreported deferrable risk (UDR) and reasons to donate were evaluated
      with data from a mail survey. RESULTS: Transfusion history was reported by 4.2
      percent of donors. Prevalence and incidence of HIV and HBV were comparable
      between transfused and nontransfused donors. Although HCV incidence was similar
      in both groups, HCV prevalence was nearly three times higher in transfused than
      in nontransfused first-time donors. UDR and reasons to donate were similar in the
      two groups, except transfused donors were less likely to donate for screening
      test results (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). CONCLUSION:
      Transfused and nontransfused donors had similar viral incidence and comparable
      UDR, suggesting that indefinite deferral of transfused donors would unlikely
      improve blood safety. Until more is known about the prevalence and transfusion
      transmissibility of emerging agents, indefinite deferral of previously transfused
      donors in the US does not appear warranted.

PMID- 15265132
TI  - Training physicians in the discipline of transfusion medicine--2004.

PMID- 15265133
TI  - The lower limit of residual white blood cell counting: how low is low?

PMID- 15265135
TI  - Controlling specimen misidentification in parentage analysis.

PMID- 15265136
TI  - Nonhemolytic passenger lymphocyte syndrome with anti-Jk after allogeneic
      peripheral blood progenitor cell transplantation.

PMID- 15265137
TI  - Splenic rupture after granulocyte-colony-stimulating factor mobilization in a
      peripheral blood progenitor cell donor.

PMID- 15265138
TI  - Multisite trial of a pH paper and a pH value of less than 7.0 to screen whole
      blood-derived platelets: implications for bacterial detection.

PMID- 15265141
TI  - Disordered eating and exercise.

PMID- 15265142
TI  - Myocardial perfusion after marathon running.
AB  - We investigated the effects of acute prolonged exercise (marathon running) on
      cardiac function and myocardial perfusion. Cardiac dimensions and function were
      measured in seven endurance-trained men using echocardiography before and
      repeatedly after marathon (42.2 km) running (at 10 min, 150 min, and 20 h).
      Myocardial perfusion and perfusion resistance were measured using positron
      emission tomography and 15O-H2O before and 85-115 min after running.
      Echocardiographic indices showed only mild and clinically non-significant changes
      in cardiac function after running. Rate-pressure-corrected basal myocardial
      perfusion (0.89+/-0.13 vs. 1.20+/-0.32 mL min(-1) g(-1), P=0.04) was increased
      after running. Also, adenosine-stimulated perfusion tended to be higher (3.67+/
      0.81 vs. 4.47+/-0.52 mL min(-1) g(-1), P=0.12) and perfusion resistance during
      adenosine stimulation was significantly lower after running (26+/-6 vs. 18+/-3
      mmHg min g mL(-1), P=0.03). Plasma free fatty acid (FFA) concentration was
      significantly increased after running. These results show that marathon running
      does not cause marked changes in cardiac function in healthy men. Basal perfusion
      was increased after exercise, probably reflecting changes in fuel preferences to
      increased use of FFAs. Strenuous exercise also seems to enhance coronary
      reactivity, which could thereby serve as a protective mechanism to vascular
      events after exercise.

PMID- 15265143
TI  - Abnormally elevated intramuscular pressure impairs muscle blood flow at rest
      after exercise.
AB  - We used photoplethysmography (PPG) to measure the relative changes in the
      anterior tibial muscle blood flow (MBF) in response to exercise when
      intramuscular pressure (IMP) was elevated (the test leg) or when IMP was normal
      (the control leg). The elevated IMP was induced by applying venous obstruction of
      40 mmHg or 65 mmHg (thigh tourniquet) of a casted leg in eight healthy subjects.
      Subjects performed dorsiflexion of both feet in sitting position with or without
      venous obstruction. IMP at rest after exercise increased to 39.4+/-7.9 mmHg or to
      58.3+/-8.4 mmHg, respectively. MBF at rest before exercise was 100%. At rest
      after exercise, it increased to 184+/-52.6% in the test leg when IMP was 39.4
      mmHg, and to 279+/-108.3% in the control leg. MBF at rest after exercise was
      156+/-58.2% in the test leg when IMP was 58.3 mmHg and 303+/-95.3% in the control
      leg. The abnormally elevated IMP induced by venous obstruction of a casted leg
      reduced MBF at rest after exercise. PPG seems to be a suitable method to measure
      changes in MBF in response to exercise and in experimental conditions with
      abnormally elevated IMP.

PMID- 15265144
TI  - Back muscle fatigue during intermittent prone back extension exercise.
AB  - The purpose of this study was to estimate the level of muscular activation and
      muscle fatigue of the low back muscles during the performance of an intermittent
      prone back extension (PBE) exercise. Forty-one healthy students (24 males and 17
      females) lying prone on a bench with the legs fixed performed two maximal
      voluntary contractions (MVC) in extension, a maximum of 100 repetitions of an
      intermittent PBE exercise immediately followed by a final MVC in extension. In
      addition, 12 subjects (11 males and one female) repeated the PBE exercise but
      with the addition of a 45-N weight on the back. The PBE exercise consisted of a
      task broken into four 1-s segments, while lying prone on a bench (10 degrees
      below horizontal): (1) raising the trunk to a horizontal position; (2) holding
      the trunk in the static phase (10 degrees above horizontal); (3) returning to the
      original position; and (4) resting on the bench. Electromyography (EMG) was used
      to measure the level of muscle activity (erector spinae (ES), gluteus maximus
      (GM), hamstrings (HA)) relative to the maximum voluntary EMG (MVE). RESULTS: Most
      of the subjects (34 out of 41) completed the 100 repetitions without excessive
      muscle fatigue according to the post-exercise MVC values. The intermittent PBE
      increased fatigue in the lumbar and hip extensor muscles in terms of: (1) a
      decrease in the MVC; (2) an increase in the level of muscle activation; and (3) a
      decline of the median frequency (MF). There was no gender difference in all EMG
      measurements. The level of muscle activation in the hip extensors (GM and HA) was
      associated with task failure (number of repetitions <100) for some subjects and
      the addition of a weight of 45 N had more impact on HA than ES. In conclusion,
      the PBE exercise as performed in the present study (including rest intervals),
      although not very strenuous for our healthy subjects, seems an adequate exercise
      to measure and train the aerobic capacity of the back muscles. However, to train
      specifically the back muscles, the exercise must be adjusted to avoid task
      failure due to possible hip extensor fatigue.

PMID- 15265145
TI  - Isokinetic performance at diagonal pattern and shoulder mobility in elite
      overhead athletes.
AB  - The purpose of this study was to measure isokinetically glenohumeral joint
      movement peak torque and work in professional basketball, volleyball, handball
      and baseball players and determine whether significant differences exist between
      the dominant and non-dominant extremity in athletes and controls. Eighty healthy
      professional overhead athletes (basketball, volleyball, handball and baseball
      players) and 20 controls were tested bilaterally on a CYBEX 6000 isokinetic
      dynamometer at 60 degrees and 180 degrees s(-1) for diagonal pattern of the
      glenohumeral joint. A standardized protocol and testing guidelines were strictly
      followed. The range of motion of internal rotation (IR) on the dominant side of
      baseball players was significantly smaller than those on the dominant side of
      basketball, handball and volleyball players, and controls (P<0.01).
      Flexion/abduction/external rotation were consistently higher on the dominant arm
      (8.5%) for peak torque at 60 degrees s(-1) in baseball players, and bilateral
      ratios were lower on the dominant arm (14.8%) for peak torque at 180 degrees s(
      1) in basketball players. The results of this study are important for the
      application and interpretation of isokinetic data and flexibility and mobility
      characteristics on unilaterally dominant overhead athletes. Functional weakness
      in external rotators, mobility impairments in IR and muscle imbalance have been
      shown in the dominant arm of these overhead athletes.

PMID- 15265146
TI  - Modification of stretch tolerance in a stooping position.
AB  - A stooping (slump) position is believed to add tension to the nerve tissue
      complex. This study was designed to determine whether this position would have an
      effect on the stretch tolerance in a passive knee extension. Thirteen healthy
      individuals were tested. The knee extension was stopped by the subjects at "onset
      of pain". Joint range of motion and passive resistance to the extension were
      recorded in four test situations: upright sitting and stooping position, with the
      ankle joint in either the neutral or maximal dorsi-flexed position. A significant
      decrease in range of motion was seen when shifting from upright to stooping
      position: Delta angle -2.4 degrees (P<0.01). According to this, the passive
      tissue tension was accepted at significantly lower values in stooping position:
      Delta torque -1.2 N m (P<0.01). Testing with maximal dorsi-flexion of the ankle
      showed more pronounced changes: Delta angle -3.4 degrees (P<0.001); Delta torque 
      2.3 N m (P<0.001), but the effect of foot position was not significant. Knee
      joint range of motion was acutely diminished in a stooping position. Thus,
      stretch tolerance was affected by manipulation of structures, which were not
      directly mechanically related to this joint. An influence from the nerve tissue
      complex must be considered to be a factor when describing the mechanisms behind
      altered stretch tolerance.

PMID- 15265147
TI  - The Coach-Athlete Relationship Questionnaire (CART-Q): development and initial
      validation.
AB  - The purpose of the present study was to develop and validate a self-report
      instrument that measures the nature of the coach-athlete relationship. Jowett et
      al.'s (Jowett & Meek, 2000; Jowett, in press) qualitative case studies and
      relevant literature were used to generate items for an instrument that measures
      affective, cognitive, and behavioral aspects of the coach-athlete relationship.
      Two studies were carried out in an attempt to assess content, predictive, and
      construct validity, as well as internal consistency, of the Coach-Athlete
      Relationship Questionnaire (CART-Q), using two independent British samples.
      Principal component analysis and confirmatory factor analysis were used to reduce
      the number of items, identify principal components, and confirm the latent
      structure of the CART-Q. Results supported the multidimensional nature of the
      coach-athlete relationship. The latent structure of the CART-Q was underlined by
      the latent variables of coaches' and athletes' Closeness (emotions), Commitment
      (cognitions), and Complementarity (behaviors).

PMID- 15265148
TI  - Gender, eating behavior, and personality characteristics in physically active
      students.
AB  - The aim of this paper was to examine associations between personality traits,
      eating disorder (ED) behavior, exercise, and gender. The participants (n=1482:
      905 women and 577 men) were students from four universities in Norway. The
      subjects filled out a compound questionnaire including demographics, weekly hours
      of exercise, type of sport, Karolinska Scales of Personality (KSP), and the
      Eating Disorder Inventory (EDI). Because of the data collection procedure, it is
      difficult to provide a clear-cut response rate in this study. The results showed
      that the risk ratio for women who scored 40 or higher on the EDI was three times
      higher compared with men. ED behavior did not seem to be associated with high
      weekly hours of physical activity in general. There were significant gender
      differences in personality traits. However, women and men with high scores on the
      EDI showed no differences on the KSP scales, except on "detachment" and "indirect
      aggression". The most important predictors for weekly hours of physical activity
      were the EDI scales "drive for thinness" and "body dissatisfaction", and the
      personality variables "extraversion" and "neuroticism". The factors that
      contributed most to the differences between students who scored 40 or higher on
      the EDI and those who scored below 40 on the EDI were neuroticism, BMI, gender,
      and age.

PMID- 15265149
TI  - Preliminary results of colour Doppler-guided intratendinous glucocorticoid
      injection for Achilles tendonitis in five patients.

PMID- 15265151
TI  - Tendinopathy--tendinitis or tendinosis? The question is still open.

PMID- 15265152
TI  - Quantitative measurement of cytomegalovirus load in pediatric solid transplant
      recipients: moving beyond antigenemia.

PMID- 15265153
TI  - Renal transplantation and long-term graft survival for all children and
      adolescents with end-stage renal failure.

PMID- 15265154
TI  - Parental experience with living-related donor liver transplantation.

PMID- 15265155
TI  - The use of multiple transbronchial biopsies as the standard approach to evaluate
      lung allograft rejection.
AB  - Flexible bronchoscopy with transbronchial biopsy (TBB) is routinely performed in
      adult and pediatric lung transplant recipients. The clinical signs and symptoms
      of acute cellular rejection (ACR) are often identical to those of infection. TBB
      is a fairly sensitive and specific tool in which to diagnose ACR and can be
      performed safely in children of all ages. The utility of TBB is unquestioned
      during periods of worsening clinical symptoms. The utility of TBB for routine
      surveillance of the allograft remains unproven. The data suggests that during the
      first 4-6 months post-transplant there is a high incidence of clinically silent
      ACR. The significance of subclinical rejection in lung transplantation is
      unknown. Randomized, controlled trials are required to determine if multiple
      surveillance TBB, can impact the incidence of obliterative bronchiolitis.

PMID- 15265156
TI  - Outcomes after renal transplantation for FSGS in children.
AB  - Focal segmental glomerulosclerosis (FSGS) is the primary diagnosis resulting in
      end-stage renal disease in approximately 12% of children receiving renal
      transplantation. Recurrent FSGS after transplantation is unpredictable and clear
      risk factors have not been identified. Post-transplantation, the incidence of
      acute tubular necrosis requiring dialysis is higher in children with FSGS
      compared with other diagnoses and may represent immediate severe recurrence.
      Graft survival is decreased in children with FSGS compared with other primary
      diagnoses, and the impact is greatest in recipients of living donor transplants.
      Graft loss caused by recurrent FSGS is significantly higher in living donor
      transplants compared with cadaveric donor transplants in children. Compared with
      adults, the impact of FSGS on graft survival appears to be greatest in children.
      White recipient race is associated with a higher risk of graft loss from
      recurrent FSGS. Efforts to elucidate the mechanisms of recurrent FSGS and to
      understand risk factors based on genetics, potential circulating cytokines and
      permeability factors, age and race must move forward before we can significantly
      impact outcomes in renal transplantation for FSGS.

PMID- 15265157
TI  - Renal transplantation in patients with IgA mesangial glomerulonephritis.
AB  - Most patients with IgA nephritis are suitable candidates for renal
      transplantation. In about 33% of patients the disease may recur after
      transplantation, although there are differences in the various series because of
      the different criteria for biopsy, the different length of follow-up and the
      different ethnicities. Living donation, genetic factors and time of progression
      of original disease have been found to be related with the risk of recurrence by
      some investigators, but these associations were not confirmed by other studies.
      The graft survival in patients with IgA nephritis is similar or even better than
      that observed with other renal diseases. The available data indicate that
      recurrence has a little impact on the 10-yr graft survival. However, a minority
      of patients may show a rapid progressive course after recurrence. Little
      information is available on the impact of recurrence in the very long term. There
      is no established treatment for preventing or treating the recurrence of IgA
      nephritis.

PMID- 15265158
TI  - Glomerular albumin permeability as an in vitro model for characterizing the
      mechanism of focal glomerulosclerosis and predicting post-transplant recurrence.
AB  - The putative mechanisms of proteinuria in idiopathic focal glomerulosclerosis and
      of its post-transplant recurrence are discussed. It is proposed that a balance
      between circulating factors with permeability activity on glomeruli and putative
      inhibitors play a key role. The characterization of inductors is currently in
      progress; most inhibitors appear to be apolipoproteins (mainly apoJ and apo E)
      but we cannot exclude other substances. The goal is now to evaluate the
      concentration of both inducers and inhibitors of glomerular permeability in vivo.
      Permeability activity in plasma of patients with FSGS with and without recurrence
      of the disease may be evaluated by an in vitro functional essay with isolated
      glomeruli. Published data on permeability activity evaluated with this method in
      different proteinuric states gave, however, controversial results and this test
      cannot be readily considered of clear clinical utility. Only the definitive
      characterization and quantification in vivo of the different molecules that play
      a role in FSGS may furnish adequate answer.

PMID- 15265160
TI  - Recurrent and de novo disease after renal transplantation: a report from the
      Renal Allograft Disease Registry.
AB  - Recurrent and de novo disease is an increasing problem and is known to negatively
      impact transplant graft survival. Immunosuppressive medications have not had an
      impact on the prevalence of recurrent and de novo disease. Renal Allograft
      Disease Registry (RADR) was established to study the prevalence, impact and risk
      factors for the development of recurrent and de novo disease. Retrospective and
      prospective study on recurrent disease is discussed in this manuscript.

PMID- 15265159
TI  - The pediatric nephrotic syndrome spectrum: clinical homogeneity and molecular
      heterogeneity.
AB  - Idiopathic nephrotic syndrome is the most common glomerular disorder of
      childhood. Recurrence of nephrotic syndrome immediately following renal
      transplantation is rapid, results in a high rate of graft loss, and represents
      the most severe form of nephrotic syndrome. This review discusses the molecular
      heterogeneity of pediatric nephrotic syndrome across the spectrum of disease
      activity. A schema is offered for a molecular approach to pediatric nephrotic
      syndrome, including immune-mediated and structural/genetic factors.

PMID- 15265161
TI  - Allograft diabetic nephropathy may progress to end-stage renal disease.
AB  - Mesangial expansion and glomerular basement membrane thickening characteristic of
      diabetic nephropathy recur in diabetic recipients of renal allografts from non
      diabetic donors but progression to renal failure is minimally documented. Three
      female renal allograft recipients (aged 40, 62 and 73 yr), who developed end
      stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients)
      and de novo diabetes (one patient) are reported. Onset of proteinuria,
      uncontrolled hypertension, azotemia, renal allograft pathologic findings and the
      need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two
      living related) had known diabetes or perturbed glucose metabolism pre
      transplantation. The three patients presented had different varieties of
      diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In
      each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8
      9) post-transplantation and increased to the nephrotic range (3.7-4.8 g/day)
      inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft
      diabetic nephropathy was made in a mean of 11.7 yr (range 10-14), based on
      glomerular basement membrane thickening, nodular and diffuse intercapillary
      glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular
      basement membrane thickening characteristic of advanced diabetic nephropathy. All
      three patients manifested uremia and resumed hemodialysis. Two patients died from
      sepsis within 2 months and one patient died 2.5 yr later after resumption of
      maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy
      in renal allografts follows a clinical decade-long course irrespective of
      diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been
      limited because of shorter survival of diabetic transplant recipients and few
      kidney biopsies performed in patients with chronic allograft dysfunction. The
      occurrence of allograft diabetic nephropathy in some, but not all patients,
      however, suggests that individual genetic variability modulates disease
      expression.

PMID- 15265162
TI  - Treatment of osteopenia and osteoporosis in renal transplant children and
      adolescents.
AB  - Successful renal transplantation corrects many of the metabolic abnormalities
      associated with the development of renal osteodystrophy, but despite a well
      functioning graft osteopenia, growth failure, spontaneous fractures, and
      avascular necrosis remain prevalent in adult and pediatric kidney recipients. A
      paucity of information exists regarding the effects of different therapies to
      prevent and treat bone loss in the renal transplant recipients. We constructed a
      design to study the effect of different modalities of treatment on bone mass in
      our renal transplant children. Among 93 patients who underwent renal
      transplantation at the age of 17 yr or less and were subjected to dual-energy X
      ray absorptiometry (DEXA), we blindly randomized 60 patients who had osteopenia
      or osteoporosis (T-score = -1 by DEXA) in a prospective study. Their mean age at
      time of transplantation was 13.4 +/- 4.3 yr. The mean duration after
      transplantation was 48 +/- 34 months. The patients were classified randomly into
      four groups. Each group consisted of 15 patients: group 1 was the control group,
      group 2 received oral alfacalcidol 0.25 microg daily, group 3 received oral
      alendronate 5 mg daily, and group 4 received 200 IU/day nasal spray calcitonin.
      Parameters of bone turnover, calcium metabolism, and DEXA were measured before
      and after 12 months of treatment duration. The characteristics of all groups were
      comparable at the beginning of the study. At the lumber spine, bone mass density
      decreased from -2.4 to -2.8 in group 1, increased from -2.3 to -0.5 in group 2,
      from -2.3 to -1.9 in group 3, and from -2.3 to -1.0 in group 4. The four groups
      had similar patient profiles, serum creatinine, intact parathyroid hormone,
      osteocalcin, and deoxypyridinoline. This study confirmed the value of
      alfacalcidol and antiresorptive agents in the treatment of osteopenia and
      osteoporosis in young renal transplant recipients.These therapies were safe,
      tolerable, simple to administer and potentially applicable to other renal
      transplant patients.

PMID- 15265163
TI  - Improvement in renal function and rejection control in pediatric liver transplant
      recipients with the introduction of sirolimus.
AB  - Calcineurin inhibitors have dramatically improved the outcomes of pediatric liver
      transplantation. However, calcineurin inhibitor use is associated with a 50%
      reduction in glomerular filtration rate in the first year post-transplant.
      Nephrotoxicity can be difficult to manage, especially in the pediatric
      population. We hypothesized that the addition of an mTOR inhibitor with decreased
      calcineurin inhibitor levels might improve or prevent renal insufficiency and
      improve control of rejection. A retrospective chart review was performed on the
      patients treated with sirolimus who had undergone an orthotopic liver transplant
      between January 2000 and February 2003. Thirty-eight patients were identified.
      Mean age was 8.6 yr. Fourteen patients were male and 24 were female. Mean weight
      was 30.3 kg. The most common indications for starting sirolimus were rejection
      (42%) and renal impairment (29%). Seventy-three percent of patients begun on
      sirolimus remain on the medication. Those with renal impairment (11 patients)
      showed improvement in their creatinine levels from a mean baseline of 1.3 to 0.8
      mg/dL. Their calculated creatinine clearance (Schwartz formula) improved from
      63.7 to 84.8 mL/min (p = 0.03). Patients started on sirolimus for rejection
      showed significant improvement in hepatocellular enzymes despite a reduction in
      the tacrolimus level from 12.2 to 7.5 ng/mL. The mean alanine aminotransferase
      level improved from 221 to 100 units/L (p = 0.02), and the mean aspartate
      aminotransferase improved from 121 to 99 units/L (p = 0.59). Addition of
      sirolimus to a tacrolimus-based regimen with lower target tacrolimus levels
      improved liver function in patients with rejection. Addition of sirolimus
      significantly improved renal function as shown by creatinine level and calculated
      creatinine clearance in those children with renal impairment. The effect of
      combined immunosuppressant treatment with tacrolimus and sirolimus on long-term
      renal function needs to be evaluated.

PMID- 15265164
TI  - Impact of non-compliance on outcome after pediatric kidney transplantation: an
      analysis in racial subgroups.
AB  - Renal transplantation is the therapy of choice for children with end-stage renal
      disease. Despite excellent patient survival, long-term graft survival is poor,
      especially in the African-American (AA) population. This article addresses non
      compliance as a major cause of late-term graft loss in the pediatric population.
      Between July 1995 and September 2002, a total of 50 pediatric kidney transplants
      were performed at our institution. We have analyzed data for 44 of these kidney
      transplants. Twelve recipients were AA, 14 Caucasian (C) and 18 Hispanic (H). The
      remaining six patients of different racial origin were not included in this
      analysis. The mean age of the recipients was 10.9 yr (range 1.7-17.8). Thirty-one
      were cadaveric and 13 were living donor transplants. We analyzed creatinine level
      and graft and patient survival at 1, 3 and 5 yr post-transplant. Compliance was
      evaluated based on trends in cyclosporine levels, attendance to clinic visits,
      individual interviews and unexplained late graft dysfunction. One- and 3-yr
      patient survival rates were 100% for all racial groups, except the 3-yr patient
      survival rate for C, which was 86%. One and 3-yr graft survival rates for AA, C
      and H were 92 and 67%, 86 and 79% and 100 and 100%, respectively. However, at 5
      yr, we found that AA recipients had a significantly higher rate of graft loss
      when compared to both H and C recipients (42 vs. 95 vs. 71%, respectively). Non
      compliance was the main factor, accounting for 71% of cases of late graft loss.
      In conclusion, non-compliance is a problem of great importance in the pediatric
      transplant population, particularly in AA recipients, where it plays a major role
      in late-term graft loss.

PMID- 15265165
TI  - The essence of living parental liver donation--donors' lived experiences of
      donation to their children.
AB  - The use of living parental liver donors will continue and probably increase
      because of lack of cadaveric livers for paediatric transplantation and the
      excellent graft survival of parental livers. Therefore, it is important for the
      health care professionals involved in living parental liver donation to
      understand the experience of being a liver donor. The aim of this study was to
      investigate the expressed deeper feelings of parents who donated a part of their
      liver to their own child. The study took the form of in-depth interviews with 11
      donors. All donors were biological parents of the recipient, nine fathers and two
      mothers. The interpretive phenomenology method was used, and interpretive
      analysis was carried out in three interrelated processes in line with Benner.
      Data collection was guided by the researcher's preliminary understanding of the
      donor experience from being involved in the surgery and care of the donors as
      well as the paediatric recipients. However, the research question was approached
      from the perspective of holistic care for the donor. In this study, the essence
      of living parental liver donation was found to be the struggle for holistic
      confirmation. There were three categories leading to this central theme; the
      total lack of choice, facing the fear of death and the transition from health to
      illness. There was total agreement among the respondents that there is no choice
      when it comes to the question of donation. The findings in this study stress the
      importance of organizing the parental liver donation programme with as much focus
      on the donor as on the child. Based on the results of this study, several
      clinical implications are suggested for the formation of guidelines for living
      parental liver donation.

PMID- 15265166
TI  - Long-term renal function in pediatric liver and heart recipients.
AB  - Long-term survivors of pediatric liver and heart transplantation are at risk for
      progressive renal dysfunction as a result of chronic exposure to calcineuron
      inhibitors. This class of drugs causes alterations in renal perfusion that can
      result in irreversible renal injury including afferent arteriopathy,
      glomerulosclerosis, tubular atrophy and interstitial fibrosis. Approximately 3-6%
      of pediatric liver and heart recipients will develop end stage renal failure. A
      much larger percentage has chronic renal insufficiency and hypertension. Children
      with significant renal compromise in the pretransplant period and those with
      significantly elevated serum creatinine levels during the first post-transplant
      year may be at the highest risk to develop irreversible renal injury in long-term
      follow-up. Serum creatinine is a poor screening tool as it rises late in the
      course when the injury may no longer be reversible. Strategies to minimize long
      term exposure to calcineuron inhibitors may reduce the prevalence of renal
      insufficiency in this vulnerable population.

PMID- 15265167
TI  - Risk factors for cardiovascular disease in pediatric renal transplant recipients.
AB  - About 1,000 children develop end-stage renal disease (ESRD) each year in the
      United States and about 5,000 children are currently receiving dialysis. Children
      who develop ESRD are eligible to receive renal replacement therapy, including
      renal transplantation. There are inherent risks associated with transplantation,
      including renal insufficiency, infections, post-transplant lymphoproliferative
      disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in
      pediatric renal transplant recipients include renal insufficiency,
      hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and
      hyperglycemia/insulin resistance. Despite evidence that many children may possess
      various risk factors for CVD post-renal transplantation, there are very few
      studies that have attempted to assess the link between these risk factors and CVD
      in pediatric renal transplant recipients.

PMID- 15265168
TI  - Hypertension and end-organ damage in pediatric renal transplantation.
AB  - The prevalence of hypertension in pediatric patients with renal transplant (Tx)
      has not changed for the last three decades, remaining at 50-80%. Long-standing
      and uncontrolled hypertension is associated with the development of end-organ
      damage including allograft dysfunction, early cardiomyopathy and premature
      atherosclerosis. Aggressive treatment of elevated BP is an essential part of Tx
      care with the goal to delay graft failure and prevent the development of
      symptomatic cardiovascular disease in young recipients of renal Tx.

PMID- 15265169
TI  - Osseous complications of pediatric transplantation.
AB  - Adult stature and peak bone mass are achieved through childhood growth and
      development. Multiple factors impair this process in children undergoing solid
      organ transplantation, including chronic illness, pretransplant osteodystrophy,
      use of medications with negative impact on bone, and post-transplant renal
      dysfunction. While growth delay and short stature remain common, the most severe
      forms of transplant-related bone disease, fracture and avascular necrosis, appear
      to have become less common in the pediatric age group. Osteopenia is very
      prevalent in adult transplant recipients and probably also in pediatrics, but its
      occurrence and sequelae are difficult to study in these groups due to
      methodological shortfalls of planar densitometry related to short stature and
      altered patterns of growth and development. Although the effect on lifetime peak
      bone mass is not clear, data from adult populations suggest an elevated long-term
      risk of bone disease in children receiving transplants. Optimal management of
      pretransplantation osteodystrophy, attention to post-transplant renal
      insufficiency among both renal and non-renal transplant patients, reduction of
      steroid dose in select patients, and supplementation with calcium plus vitamin D
      during expected periods of maximal bone loss may improve bone health. Careful
      research is required to determine the role of bisphosphonate therapy in pediatric
      transplantation.

PMID- 15265170
TI  - Liver retransplantation in an infant requiring cavoportal hemi transposition.
AB  - Historically inability to achieve portal inflow to the liver allograft
      operatively was felt to be a contraindication to orthotopic liver transplantation
      (OLTx). Cavoportal hemi transposition has been utilized more recently in adult
      OLTx recipients but rarely in pediatric recipients. Here we report the case of a
      10-month-old male with biliary atresia, who required urgent retransplantation
      with an in situ split cadaver donor allograft for failure of his first liver
      allograft from portal vein thrombosis. At the time of retransplantation,
      cavoportal hemi transposition was required to effect portal vein inflow to the
      allograft because of extensive thrombosis of the recipients portomesenteric
      venous system.

PMID- 15265171
TI  - Role of leptin in farm animals: a review.
AB  - The discovery of hormone leptin has led to better understanding of the energy
      balance control. In addition to its effects on food intake and energy
      expenditure, leptin has now been implicated as a mediator of diverse
      physiological functions. Recently, leptin has been cloned in several domestic
      species. The sequence similarity suggests a common function or mechanism of this
      peptide hormone across species. Leptin receptors are expressed in most of
      tissues, which is consistent with the multiplicity of leptin functions. The main
      goal of this review was to summarize knowledge about effect of leptin on
      physiology of farm animals. Experiments point to a stimulatory action of leptin
      on growth hormone (GH) secretion, normal growth and development of the brain.
      Surprisingly, leptin is synthesized at a high rate in placenta and may function
      as a growth factor for fetus, signalling the nutritional status from the mother
      to her offspring. Maturation of reproductive system can be stimulated by leptin
      administration. Morphological and hormonal changes, consistent with a major role
      of leptin in the reproductive system, have also been described, including the
      stimulation of the release of luteinizing hormone (LH), follicle-stimulating
      hormone (FSH) and prolactin. Leptin has a substantial effect on food intake and
      feeding behaviour in animals. Administration of leptin reduces food intake. Its
      level decrease within hours after initiation of fasting. Leptin also serves as a
      mediator of the adaptation to fasting, and this role may be the primary function
      for which was the molecule evolved.

PMID- 15265172
TI  - Growth of differentiated ovine tracheal epithelial cells in vitro.
AB  - Culture of ovine tracheal epithelial cells is a useful tool for conducting
      various in vitro studies. We describe herein an in vitro technique and the
      conditions for culturing primary epithelial cells derived from tracheas of adult
      sheep. Ovine tracheas were surgically removed from 2- to 3-month-old healthy
      sheep and tracheal epithelial cells were isolated by 0.15% pronase digestion.
      After epithelial cells isolation, a Millicell insert with porous membrane was
      coated with 0.05% human placental collagen and the epithelial cells were added to
      the membrane. To create an air-liquid interface environment for the cells, the
      apical compartment of the membrane containing the tracheal epithelial cells was
      left exposed to 5% CO(2) at 37 degrees C for 2 days then increased to 9% CO(2)
      while cells in the basolateral compartment underneath the membrane contained the
      growth medium necessary for cells nourishment. Pepsin digestion was more
      effective in reducing the number of fibroblasts than other procedures. Cells were
      allowed to grow for 6-7 days to form a confluent monolayer and nearly 21 days for
      cilia formation on the apical surface as determined by light microscopy of
      haematoxylin and eosin-stained sections of membranes. In order to further confirm
      the epithelial origin of cells, cells were stained for cytokeratin antigen by
      immunohistochemistry. Most ciliated epithelial cells were immunoreactive for
      cytokeratin. This is the first report of differentiated ovine tracheal epithelial
      cells growth and isolation. This technique can be used in numerous in vitro
      investigative studies in ovine species as an animal model for human disease.

PMID- 15265173
TI  - Comparison of the effects of fructose and glucose supplementation on metabolic
      responses in resting and exercising horses.
AB  - The aim of this study was to compare the effects of two different carbohydrate
      sources (fructose and glucose) on the metabolic responses in resting and
      exercising horses. The following regimes were fed in randomized order to five
      trained horses at rest and immediately before or during exercise. The resting
      regime comprised 0.6 kg grass meal pellets (control) or 0.6 kg grass meal pellets
      supplemented with either 50% glucose or 50% fructose. The exercise regime
      comprised 0.3 kg grass meal (control) or 0.6 kg grass meal pellets supplemented
      with either 50% glucose or 50% fructose fed immediately before or during
      simulated endurance exercise on a treadmill (30 km, total running time 120 min;
      15 min rest after 60 min running time). Blood samples were collected for the
      analysis of glucose, insulin, free fatty acids (FFA) and lactate. In resting
      horses, glucose supplementation resulted in a significantly higher glycaemic and
      insulinaemic response than the control or fructose feedings (treatment P < 0.05).
      Plasma glucose levels were significantly higher after glucose supplementation
      given before or during exercise. Similar plasma glucose concentrations were
      observed after fructose was fed before exercise, whereas fructose supplementation
      during exercise resulted in a lower glycaemic response than glucose feeding (P <
      0.05). Plasma insulin, FFA and lactate levels showed exercise-related changes
      (time P < 0.05), but treatment did not effect these results. Plasma glucose
      concentrations were elevated during the simulated endurance exercise after
      glucose feeding, and no counter-regulation by insulin occurred. The higher
      glycaemic response might be beneficial as exogenous glucose can be used as an
      energetic substrate during prolonged exercise. Fructose exhibited no clear
      advantages in comparison with glucose as a carbohydrate source for exercising
      horses.

PMID- 15265174
TI  - Effect of vitamin E supplementation on various functional properties of
      macrophages and neutrophils obtained from weaned piglets.
AB  - Sixteen piglets were used to determine the effect of vitamin E supplementation on
      several functional properties of macrophages and neutrophils obtained from weaned
      piglets. Piglets, immediately following weaning, were assigned to one of three
      experimental groups: control (no vitamin E supplementation), low level of vitamin
      E supplementation (100 mg DL-alpha-tocopheryl acetate/kg diet) and high level of
      vitamin E supplementation (300 mg DL-alpha-tocopheryl acetate/kg diet).
      Supplementation of vitamin E lasted for a period of 36 days, following a 3-day
      adaptation period after weaning. Blood samples were collected on days 0, 12, 24
      and 36 of the experimental period, monocytes/macrophages and neutrophils were
      isolated and the following parameters were determined in macrophages and
      neutrophils activated by phorbol myristate acetate: total cell-associated and
      membrane-bound urokinase plasminogen activator (u-PA) activity and superoxide
      anion production. Results showed that macrophages and neutrophils isolated from
      piglets that received supplemental vitamin E had higher (P < 0.05) total and
      membrane-bound u-PA activities as well as higher (P < 0.05) superoxide anion
      production compared with the values of the corresponding cells obtained from
      control piglets on day 12 of the experimental period. Both levels of vitamin E
      supplementation (low and high) were equally effective. In contrast, vitamin E
      supplementation had no effect (P > 0.05) on total and membrane-bound u-PA
      activities and superoxide anion production by porcine macrophages and neutrophils
      on days 24 and 36 of the experimental period. In conclusion, the low level of
      vitamin E supplementation is recommended for piglets for the first 2 weeks after
      weaning.

PMID- 15265175
TI  - A comparison of biopsy and post-mortem findings in the lungs of healthy cows.
AB  - Lung biopsy in cattle for the diagnosis of lung diseases is rarely used or
      described. The clinical effects and the gross findings in lung and pleura after
      ultrasonic-guided percutaneous lung biopsy in the upright animal of healthy
      cattle were reported previously (Braun et al., 1999). This report describes the
      yield of attained lung tissue and the local tissue reaction in 60 healthy adult
      cows slaughtered 24 h (50 animals) and 10 days (10 animals) after invasion. The
      yield of lung tissue in the biopsies was high (85.5%) in 90 histologically
      examined biopsy specimens and judged 'good to excellent'. The local tissue
      reaction and the extent of haemorrhage in the lung parenchyma, both 24 h and 10
      days after the biopsy, were minimal. In the latter group, the scar tissue had
      approximately the same dimensions as the tissue cylinders punched 10 days before.
      There were no local adhesions between the pleural surfaces. Previously published
      data concerning clinical reactions and complications, macroscopically examined
      local tissue bleeding and the histologically evaluated minimal local inflammatory
      reaction, following lung biopsy of cattle, indicate that this procedure is safe
      and satisfactory for sampling of accurate lung material. The results of this
      study concur and indicate that local complications in the animal were minimal to
      absent.

PMID- 15265176
TI  - The effect of parentage on the prevalence, severity and location of lesions of
      osteochondrosis in swine.
AB  - The aims of this study were to determine the effects of parentage and gender on
      the prevalence, severity and location of lesions of osteochondrosis manifesta
      (OCM) and osteochondrosis dissecans (OCD) in offspring from different Norwegian
      Landrace boars and to examine the relationships between lesion characteristics
      and selected growth parameters. Fifteen sires were selected based on their high
      breeding value for osteochondrosis. Seven locations in the distal humerus and the
      distal femur from 1680 offspring of these animals were evaluated for severity of
      OCM and presence of OCD by gross examination of serially sectioned humeri and
      femora. Osteochondrosis manifesta was most prevalent in the trochlea of humerus,
      the sagittal ridge of humerus, the medial condyle of femur and the medial sulcus
      obliquus of femur. The severity of the lesions and the prevalence of OCD were
      highest in the trochlea and the sagittal ridge of humerus. Castrates had
      significantly higher OCM scores than sows. There were significant effects of both
      sire and dam on the OCM scores of the offspring in most locations; however,
      growth rate and weight at slaughter did not influence the OCM score.

PMID- 15265177
TI  - Evaluation of stratification factors and score-scales in clinical trials of
      treatment of clinical mastitis in dairy cows.
AB  - There is often a need to reduce sample size in clinical trials due to practical
      limitations and ethical considerations. Better comparability between treatment
      groups by use of stratification in the design, and use of continuous outcome
      variables in the evaluation of treatment results, are two methods that can be
      used in order to achieve this. In this paper the choice of stratification factors
      in trials of clinical mastitis in dairy cows is investigated, and two score
      scales for evaluation of clinical mastitis are introduced. The outcome in 57
      dairy cows suffering from clinical mastitis and included in a clinical trial
      comparing homeopathic treatment, placebo and a standard antibiotic treatment is
      investigated. The strata of various stratification factors are compared across
      treatments to determine which other factors influence outcome. The two score
      scales, measuring acute and chronic mastitis symptoms, respectively, are
      evaluated on their ability to differentiate between patients classified from
      clinical criteria as responders or non-responders to treatment. Differences were
      found between the strata of the factors severity of mastitis, lactation number,
      previous mastitis this lactation and bacteriological findings. These factors
      influence outcome of treatment and appear relevant as stratification factors in
      mastitis trials. Both score scales differentiated between responders and non
      responders to treatment and were found useful for evaluation of mastitis and
      mastitis treatment.

PMID- 15265178
TI  - Relationships between lactational incidence of displaced abomasum and milk
      production traits in German Holstein cows.
AB  - The objective of this study was to analyse the heritabilitiy of the lactational
      incidence of displaced abomasum (DA) and the relationships of DA with milk
      production traits in German Holstein cows. Data were recorded between February
      1999 and January 2000 in cooperation with five veterinary practitioners. Their
      veterinary practices were located in the northern part of Lower Saxony. The
      investigation included 160 dairy farms under the official milk-recording scheme
      with 9,315 cows. The lactational incidence of the left abomasal displacement
      amounted to 1.21%, and of the right abomasal displacement to 0.41%, respectively.
      The linear heritability estimates for the lactational incidences of left and
      right DA were h(2) = 0.05 +/- 0.012 and h(2) = 0.004 +/- 0.005, respectively.
      Using the Dempster-Lerner-transformation the corresponding heritabilities were
      h(2) = 0.53 and 0.09, respectively. Milk losses for the lactation when DA was
      diagnosed were significant and reached 1016 kg milk, 41 kg fat, 36 kg protein and
      0.07% protein. Fat content significantly increased by 0.18%. The analysis could
      not show significant differences between cows diagnosed with DA and cows not
      diagnosed with DA in the 305-day milk production traits of the lactation
      preceding the diagnosis of DA. There was also no indication for an unequal
      distribution of breeding values for milk performance traits between cows with and
      without DA. The additive genetic correlations between 305-day milk performance
      and left DA were low. The results indicated that cows with a high milk production
      and superior breeding values for milk performance were not exposed to an
      increased risk for DA.

PMID- 15265179
TI  - Research and sudden infant death syndrome: definitions, diagnostic difficulties
      and discrepancies.
AB  - The diagnosis of causes of sudden infant death is an often complex and difficult
      process. Variable standards of autopsy practice and the use of different
      definitions for entities such as sudden infant death syndrome (SIDS) have also
      contributed to confusion and discrepancies. For example, the term SIDS has been
      used when the requirements of standard definitions have not been fulfilled. In an
      attempt to correct this situation recent initiatives have been undertaken to
      stratify cases of unexpected infant death and to institute protocols that provide
      frameworks for investigations. However, if research is to be meaningful,
      researchers must be scrupulous in assessing how extensively cases have been
      investigated and how closely cases fit with internationally recognized
      definitions and standards. Unless this approach is adopted, evaluation of
      research findings in SIDS will be difficult and the literature will continue to
      be beset by contradictions and unsubstantiated conclusions.

PMID- 15265180
TI  - Iron deficiency in minority groups in Australia.

PMID- 15265181
TI  - Iron status of young Vietnamese children in Australia.
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence of iron
      deficiency in Vietnamese children living in Australia and to identify risk
      factors associated with iron deficiency. METHODS: A cohort of healthy term
      Vietnamese infants, were followed from birth (n = 210) to 18 months (n = 174)
      with anthropometry, dietary intake and feeding practices measured at seven time
      points. Socio-demographic data were collected from the parents at the first home
      visit. At 18 months iron status was examined by full blood count and plasma
      ferritin concentration in 129/152 (85%) of the eligible children. Iron depletion
      was defined as a plasma ferritin level < 10 microg/L. Iron deficiency without
      anaemia was defined as iron depletion plus MCV < 70fl and iron deficiency anaemia
      was defined as iron deficiency anaemia plus Hb < 110 g/L. RESULTS: The prevalence
      of iron deficiency was iron depletion 19.4% (95% CI: 13.0%, 27.3%), iron
      deficiency without anaemia 3.1% (95% CI: 0.9%, 7.8%) and iron deficiency anaemia
      3.9% (95% CI: 1.3%, 8.8%). Multiple regression analysis showed three significant
      predictors of iron deficiency: cows milk intake (negative effect), meat, fish or
      poultry intake (positive effect) and weight gain (negative effect). A cows milk
      intake > or = 650 mL/day was a risk factor for iron deficiency. CONCLUSION:
      Prevalence of iron deficiency at 18 months was high despite appropriate infant
      feeding practices during the first year. Modification of the diet in the second
      year of life may decrease the risk of iron deficiency in Vietnamese children.

PMID- 15265182
TI  - Iron status and haematological changes in adolescent female inpatients with
      anorexia nervosa.
AB  - OBJECTIVES: (i) To investigate the incidence of iron deficiency (both latent iron
      deficiency and iron deficiency anaemia) in post menarchal female adolescent
      patients hospitalized with anorexia nervosa. (ii) To observe changes in iron
      status during refeeding. METHODS: During the study period all post menarchal
      female patients admitted to the adolescent unit with anorexia nervosa were
      invited to participate. Ferritin, serum iron, transferrin and transferrin
      saturation were measured on admission and discharge. Haemoglobin, haematocrit,
      weight, and body mass index were monitored weekly. RESULTS: All 12 eligible
      patients participated in the study. Four patients had elevated ferritin levels on
      admission. Ten of the 12 showed a statistically significant fall in serum
      ferritin at time of discharge compared with admission (P = 0.004). One of 12
      patients had a low serum iron at presentation. All 12 had normal serum iron
      levels at discharge. Nine of the 12 subjects had a higher serum iron at discharge
      which was statistically significant (P = 0.046). There was no significant change
      in haemoglobin levels when comparing admission and discharge levels. Nine of the
      12 patients however, transiently developed anaemia, at some stage during
      treatment. CONCLUSIONS: Iron deficiency is uncommon at both presentation and
      after nutritional rehabilitation in post menarchal adolescent females with
      anorexia nervosa. This is most likely due to increased iron storage secondary to
      the contraction of the circulating blood volume and reduced iron losses from
      (secondary) amenorrhoea. The fall in ferritin observed during treatment is due to
      haemopoiesis necessary to fill the increased blood volume associated with weight
      gain. This also results in normalization of the haemoglobin and haematocrit.

PMID- 15265183
TI  - Asthma in emergency departments: combined adult and paediatric versus paediatric
      only centres.
AB  - OBJECTIVE: To compare the management of paediatric patients with mild or moderate
      asthma in paediatric-only emergency departments (POEDs) to treatment in a mixed
      adult-child emergency departments (mixed EDs). METHODS: Prospective,
      observational study conducted in 36 Australian emergency departments (EDs) for 2
      weeks in 2001. Children aged 1-15 years with acute asthma classified as mild or
      moderate severity. Details of demography, severity assessment, and type of
      treatment facility, treatment and disposition were collected. Analysis used
      descriptive statistics, comparison of proportions by chi2, and multiple logistic
      regression. RESULTS: Two-hundred and nine children were treated at POEDs and 257
      at mixed EDs. The groups had similar severity. Spacers to deliver beta-agonists
      were used more frequently in POEDs (67.5% vs 24.2%; P < 0.01). Children treated
      at POEDs with a mild attack were more likely to be admitted (20.6% vs 9.5%; P <
      0.02) and given salbutamol (82.8% vs 71.9%; P = 0.03). For children with moderate
      asthma, oral steroid prescription on hospital discharge was more common for those
      treated in a mixed ED (81.0% vs 95.7%; P = 0.01). Ipratropium bromide (IB) was
      widely used at both types of ED but more commonly used in mixed EDs (41.7% vs
      54.9%; P < 0.01). There were no differences in length-of-stay, representation
      rate within one month and oral steroid use for attack. Less than 2/3 of children
      with mild asthma attacks received steroid treatment in the ED. CONCLUSION:
      Treatment was similar between the two types of ED. IB was overused in mild asthma
      and oral steroids were underused in moderate asthma, by both ED types. Spacers
      were under-utilized in mixed EDs.

PMID- 15265184
TI  - Predicting the need for ventilation in term and near-term neonates.
AB  - OBJECTIVE: To determine whether the need for respiratory support can be predicted
      by oxygen requirement within the first 72 h in term and near-term infants.
      METHODS: To mimic the population of infants that would often be delivered outside
      a tertiary centre we studied a retrospective cohort of infants > or = 32 weeks
      requiring oxygen, divided into three groups: cot oxygen only, nasal continuous
      positive airway pressure (NCPAP) only, or intermittent positive pressure
      ventilation (IPPV). We recorded each infant's peak fraction of inspired oxygen
      (FiO2)--i.e. FiO2 in the first 72 h in the cot oxygen only group or maximum FiO2
      prior to commencing the highest level of respiratory support. The peak FiO2 was
      used as a diagnostic test to predict any respiratory support or IPPV--sensitivity
      and specificity were calculated and receiver operating characteristic (ROC)
      curves plotted (FiO2 0.21-1.00) to identify the best balance point for
      prediction. RESULTS: The cohort included 592 infants: 516 cot oxygen only, 46
      NCPAP only and 30 IPPV. The proportion ventilated increased with increasing peak
      FiO2--above 0.45 the proportion of infants ventilated exceeded 50%. To predict
      any respiratory support, the cut-point balancing sensitivity and specificity was
      a FiO2 > or = 0.35-58/136 required respiratory support (sensitivity = 0.76,
      specificity = 0.85, positive predictive value (PPV) = 43%, negative predictive
      value (NPV) = 96%). To predict IPPV the cut-point was a FiO2 > or = 0.5-28/47
      treated with IPPV (sensitivity = 0.93, specificity = 0.97, PPV = 60%, NPV =
      100%). CONCLUSION: The need for respiratory support can be predicted by oxygen
      requirement within the first 72 h in term and near-term infants with reasonable
      sensitivity and excellent specificity.

PMID- 15265185
TI  - Perinatal cytomegalovirus hepatitis: to treat or not to treat with ganciclovir.
AB  - OBJECTIVE: The use on ganciclovir for perinatal cytomegalovirus (CMV) infection
      is controversial. We aim to evaluate the use of ganciclovir treatment for
      neonatal CMV hepatitis. METHODS: We present five infants with perinatally
      acquired CMV hepatitis as a single organ manifestation of CMV infection. The
      three more severely affected children, i.e. those with cholestasis and elevation
      of serum hepatic enzymes to more than twice the normal values, were treated for
      15 days with intravenous ganciclovir. RESULTS: The three treated infants improved
      clinically and CMV DNA in the blood disappeared during treatment. After cessation
      of ganciclovir treatment all of the patients had a relapse of the infection. The
      two untreated patients recovered completely. CONCLUSION: The long-term outcome of
      infants with CMV hepatitis is unpredictable. Some patients have persistent liver
      injury despite ganciclovir therapy. Ganciclovir therapy did not prevent chronic
      liver disease in any of the patients in our study. Owing to the possible serious
      side-effects the cost-benefit of ganciclovir treatment should be carefully
      evaluated.

PMID- 15265186
TI  - Evolution of an adenovirus outbreak in a multidisciplinary children's hospital.
AB  - OBJECTIVE: To describe the course of an evolving adenovirus outbreak in a
      multidisciplinary children's hospital with a high-risk patient population.
      METHODS: Observational study in a 280-bed university hospital during June 2002.
      Active case finding identified children with adenovirus infection. Data are
      median (interquartile range) or n (%). Adenovirus infection was diagnosed in 49
      children, median age 12 months (4-33). RESULTS: New cases were diagnosed over 26
      days and peaked on day 17 (n = 15). Total infected inpatients peaked on days 17
      21 (n = 36). Twenty-three infections (47%) were community-acquired and 26 (53%)
      hospital-acquired. Thirty-three children (67%) had a coexistent high-risk
      condition. Median hospital stay before and after diagnosis was 9 days (3-18) and
      9 days (4-29), respectively. Twenty-two children (45%) were admitted to PICU.
      Overall hospital mortality was 22% (n = 11) and mortality attributed to
      adenoviral disease 12% (n = 6). Hospital mortality was similar between community-
      and hospital-acquired infections (22% compared to 23%) (P = 1.0). Twenty children
      (41%) received intravenous immunoglobulin (IVIG). Children treated with IVIG had
      a longer hospital stay (median 40 days vs 14 days) than those who did not receive
      IVIG (P = 0.01). Neither PICU mortality (29% vs 12%), nor hospital mortality (35%
      vs 14%), differed significantly between IVIG treated and untreated children (P =
      0.76 and P = 0.16, respectively). CONCLUSION: The rapid spread of hospital
      acquired adenovirus underlines the importance of effective infection control
      measures. Despite nosocomial infection amongst high-risk patients, mortality was
      similar to that of community-acquired infection. Administration of immunoglobulin
      was not associated with demonstrable benefit. A prospective randomized trial
      would be required to resolve this issue.

PMID- 15265187
TI  - Intelligence and achievement of children referred following sexual abuse.
AB  - OBJECTIVE: Little is known about the prevalence of intellectual and academic
      problems in sexually abused children. Such problems may have significant
      implications for their management. This study examined the prevalence of such
      problems in a population of Australian children referred for sexual abuse
      evaluation. The study also assessed the clinical utility of the Parents'
      Evaluation of Developmental Status (PEDS) questionnaire as a screening tool for
      learning and developmental problems in this population. METHODS: Over a 12-month
      period, children referred for sexual abuse evaluation to the Mater Children's
      Hospital Child Protection Unit were enrolled and background demographic and abuse
      related data collected. The children then completed standardized psychometric
      assessments. Their parents completed Child Behavior Checklists (CBCL) and PEDS
      questionnaires. Day care providers and schoolteachers completed the corresponding
      Caregiver or Teacher Report Forms (TRF). RESULTS: A total of 21 of the 35
      eligible children completed the assessment during the study period. Mean scores
      for intelligence and academic achievement were within the average range. However,
      three (14%) of the tested children were intellectually impaired and three (14%)
      showed academic underachievement. Sixty-two per cent of children had problems in
      the clinical range on the CBCL and 33% on the TRF. The PEDS showed a sensitivity
      of 64%, specificity of 60% with a positive predictive value of 77%. CONCLUSION:
      In this population of referred children, over one quarter showed problems with
      intellectual impairment or academic under achievement. Most of these children
      were not receiving learning support at school. A high index of suspicion is
      therefore required when assessing sexually abused children for comorbid
      intellectual and learning problems.

PMID- 15265188
TI  - Snoring and its association with asthma in Indigenous children living in the
      Torres Strait and Northern Peninsula Area.
AB  - OBJECTIVE: Respiratory health of Indigenous and minority ethnic groups in
      affluent countries is poorer than their non-minority counterparts and sleep
      disorders are no exception. In children, obstructive sleep apnoea has the
      potential to result in serious long-term consequences. In 1999, we studied 1650
      children and adolescents living in the Torres Strait and the Northern Peninsula
      Area, Australia. Here we report prevalence of snoring in these communities and
      relate its association with asthma symptoms. METHODS: A population-based cross
      sectional study was conducted in the Torres Strait region. Five indigenous
      communities were randomly selected and information was collected using a
      structured face-to-face interview based on a standardized questionnaire. There
      was a 98% response rate, and 1650 children, 0-17 years of age, were included in
      the study. RESULTS: Overall, the prevalence of snoring was 14.2% (95% CI 12.5
      15.9); 3.6% (95% CI 2.7-4.6) reported snorting, and 6% (95% CI 4.9-7.2) reported
      restless sleep. The prevalence of snoring was significantly higher among males
      (17.1% for males and 10.8 for females, P = 0.005). Children were five times more
      likely to have experienced snoring and snorting if they reported wheezing in the
      last 12 months. CONCLUSION: We conclude that the prevalence of symptoms
      suggestive of obstructive sleep problems is relatively high in children of this
      region. This highlights the need for awareness among the community patients and
      physicians about the problem of obstructive sleep-disordered breathing,
      especially in children with asthma, and for the need for further studies to
      measure prevalence of sleep breathing disorders among Indigenous Australians.

PMID- 15265189
TI  - Notification of patients with acute flaccid paralysis since certification of
      Australia as polio-free.
AB  - OBJECTIVE: Surveillance of patients presenting with acute flaccid paralysis (AFP)
      is the World Health Organization (WHO) recommended method for the detection of
      incident cases of poliovirus infection. Australia was certified free of
      circulating poliovirus in 2000 but is required to continue AFP surveillance until
      global certification. Although Australia reached the WHO nominated surveillance
      target in 2000 and 2001, it was not reached in 2002. Notification rates between
      states have been variable. We aim to investigate the difference in notification
      rates by state to determine whether different rates reflect different patterns of
      disease or different approaches to reporting. METHODS: Notification rates were
      reviewed by state for the years 1997-2002. The completeness of case ascertainment
      was reviewed from published studies. Key informants described differences in AFP
      reporting in states with consistent differences in notification rates. RESULTS:
      Australia achieved 75% of the WHO surveillance target for AFP cases between 1997
      and 1999 and 98% between 2000 and 2002. After 2000, Queensland achieved 150% of
      its target while Victoria achieved less than 50%. New South Wales reached its
      target over the entire 6 years but other states and territories were not as
      consistent. Although the formal process for AFP reporting is uniform throughout
      Australia, many differences in approach were identified between Victoria and
      Queensland. CONCLUSION: Maintaining AFP surveillance at the required WHO standard
      will be more likely in Australia if the populous states are able to notify cases
      at the same rate as Queensland (since 2000) and New South Wales (in general).

PMID- 15265190
TI  - Bone mineral metabolism changes in epileptic children receiving valproic acid.
AB  - OBJECTIVE: The aim of this study was to evaluate bone mineral density (BMD) in
      epileptic children receiving valproic acid (VPA) and to determine differences
      between osteopenic and non-osteopenic children. METHODS: Thirty-three epileptic
      children, receiving VPA for at least 6 months, were compared with 33 healthy
      children for BMD. BMD was measured by dual-energy X-ray absorptiometry at lumbar
      vertebrae, femoral neck and greater trochanter. Serum calcium, phosphorus,
      alkaline phosphates, osteocalcin and VPA levels were also determined. RESULTS:
      Patient's osteocalcin levels were significantly higher (P = 0.02) and femur and
      trochanter BMD values were significantly lower (P = 0.04 and P = 0.03,
      respectively). Duration of VPA therapy was significantly longer and doses of VPA
      were significantly higher in seven osteopenic patients compared with 26 non
      osteopenic patients. Osteopenic patients (4.6 +/- 2.4 years) were younger than
      non-osteopenic patients (7.8 +/- 3.2 years) (P = 0.01). CONCLUSION: Long-term and
      high dose VPA therapy may cause osteopenia, primarily in younger epileptic
      children. These patients should be followed closely by BMD measurements.

PMID- 15265191
TI  - The value of a CT-guided fine needle aspirate in infants with lung abscess.
AB  - OBJECTIVE: To describe the range of pathogens isolated from a lung abscess in
      infants less than one year of age. To assess the role of direct culture from the
      abscess. METHODS: The two index cases were managed in 2002. An institution-based
      review was conducted of all infants up to one year of age diagnosed with a lung
      abscess between 1989 and 2002. Data sources were hospital's disease index and
      Neonatal Intensive Care Unit Audit database using ICD9 and ICD10 diagnostic codes
      for 'lung abscess'. RESULTS: Five infants, under the age of one year, were
      treated for a lung abscess. In the one case where the abscess was left-sided it
      was associated with a congenital cystic adenomatoid malformation of the lung.
      Pathogens were isolated following direct culture of the abscess in four cases. In
      three cases a single pathogen was isolated: pseudomonas aeruginosa,
      staphylococcus aureus and haemophilus influenzae. In one case a mixture of
      escherichia coli, streptococcus milleri and an anaerobe, propionibacteria, were
      cultured. Antibiotic therapy was directed at the identified pathogen(s) in all
      four cases. There was no mortality or recurrence. CONCLUSION: Predisposing
      factors for a lung abscess in infancy include prematurity, assisted ventilation,
      congenital lung anomaly and aspiration. Given the range of potential pathogens,
      direct culture by CT-guided fine needle aspiration is recommended to direct
      appropriate intravenous medical therapy provided the abscess is located
      peripherally.

PMID- 15265192
TI  - Development and use of a portable paediatric resuscitation card.
AB  - OBJECTIVES: Inaccuracy and delay in decision making in paediatric resuscitation
      has been previously demonstrated and may result in preventable death. We assessed
      several domains of paediatric resuscitation knowledge amongst a sample of
      tertiary hospital paediatric doctors, developed a portable aide-memoire reference
      card containing reference normal values, including an algorithm for recognition
      and management of the seriously ill/arrested child, and assessed the ability of
      medical staff to use this card to obtain accurate information. METHODS: A
      convenience sample of 46 members of the Royal Children's Hospital medical staff
      completed a questionnaire. Knowledge deficits identified were used to create a 9
      x 6 cm, name tag sized, laminated card providing physiological parameters and
      information required for paediatric resuscitation. The card was then distributed
      to all medical staff. A sample of 18 doctors completed an identical questionnaire
      4 months after introduction of the card. Pre- and post-card results were analysed
      across a range of knowledge domains. RESULTS: Basic calculations were incorrect
      in over 40% of all pre-card responses. Seniority did not predict more correct
      answers. The post-card group obtained significantly more correct answers than the
      pre-card group. CONCLUSION: Medical staff wore, and were able to use the card to
      provide the correct values for paediatric resuscitation parameters. The use of a
      card significantly improved knowledge of the correct values for resuscitation
      data. This project has resulted in the card being issued to all medical and
      nursing staff and is now accessible via the Royal Children's Hospital internet at
      http://perseus.rch.unimelb.edu.au/genmed/resuscardontheweb.htm

PMID- 15265193
TI  - Bilateral parotid abscesses in an HIV-infected child caused by Streptococcus
      pneumoniae.

PMID- 15265194
TI  - Facial nerve paralysis secondary to acute otitis media in infants and children.
AB  - Nowadays, facial paralysis is an uncommon complication of acute inflammation of
      the middle ear, with an estimated incidence of 0.005%; it was not so rare in the
      pre-antibiotic era, occurring in 0.5-0.7% of middle ear inflammatory processes.
      We would like to highlight this complication of acute otitis media, a common
      paediatric complaint. We present three new cases of facial palsy in children with
      acute otitis media and discuss the etiological mechanisms and different
      approaches to the treatment; a flow chart for facial paralysis in acute otitis
      media is also presented. Our three patients recovered completely after
      mastoidectomy (first two cases) and myringotomy with antibiotic therapy (third
      case). Facial paralysis is an uncommon complication of otitis media which
      requires appropriate care. Following our experience and revision of literature on
      the subject, antibiotic therapy and myringotomy are the first-line procedures.
      Surgery should be employed in case of acute or coalescent mastoiditis,
      suppurative complications and lack of clinical regression.

PMID- 15265195
TI  - Hereditary pancreatitis in a family of Aboriginal descent.
AB  - Hereditary pancreatitis is an autosomal dominant condition characterized by
      recurrent episodes of acute pancreatitis, usually starting in childhood. We
      present a family who was ascertained when an 11-year-old girl presented with an
      episode of acute pancreatitis. Her father and other family members had also had
      recurrent bouts of acute pancreatitis. Genetic testing revealed a pathogenic
      mutation in the cationic trypsinogen gene in the proband, her father and her
      paternal grandmother. As far as we are aware, this is the first Aboriginal
      kindred with mutation-proven hereditary pancreatitis. Hereditary pancreatitis is
      an important differential diagnosis to consider in a patient with recurrent
      episodes of acute pancreatitis with no obvious precipitating cause. This family
      is of Aboriginal descent and the implications of the family's background are also
      discussed when considering the aetiology of the condition. We emphasize the need
      to ascertain a full family history from patients with a history of repeated
      episodes of acute pancreatitis and also emphasize the need to avoid ethnic
      stereotypes when assessing patients.

PMID- 15265197
TI  - Adventitious knot formation complicating catheterization of the infant bladder.
AB  - Bladder catheterization is a common technique employed in obtaining urine for
      culture, monitoring urine output and for diagnostic radiological procedures. We
      present two cases of knot formation in male infants catheterized with a 5 gauge
      feeding tube. We discuss avoidance, recognition and management of this
      complication.

PMID- 15265196
TI  - Isoniazid and hypoglycaemia in a premature infant.
AB  - Severe hypoglycaemia requiring more than 20 mg/kg per minute glucose infusion was
      seen in a premature infant. The infant was born to a woman with active
      tuberculosis, and she was on prophylactic isoniazid. Discontinuation of isoniazid
      resulted in prompt recovery of hypoglycaemia. Further pharmacological studies may
      be needed to establish a cause and effect relationship.

PMID- 15265198
TI  - Re: resuscitation beyond 10 minutes of term babies born without signs of life.

PMID- 15265199
TI  - Occurrence of vascular rings in ex-preterm twins.

PMID- 15265207
TI  - Perceived stress, pain and work performance among non-patient working personnel
      with clinical signs of temporomandibular or neck pain.
AB  - The aim of the present study was to assess the associations between different
      types of perceived stress, pain and work performance among non-patients with
      clinical signs of muscle pain in the head/neck region. One-fifth (n = 241) of the
      1339 media employees who had participated in a previous survey (Ahlberg J. et
      al., J Psychosom Res 2002; 53: 1077-1081) were randomly selected for standardized
      clinical examinations. Altogether 49% (n = 118) of these subjects had clinical
      signs of temporomandibular and/or neck muscle pain and were enrolled in the
      present study. The mean age of the study sample was 46.9 years (s.d. 6.6) and the
      female to male distribution 2:1. Of the 118 employees 46.5% reported that the
      pain problem interfered with their ability to work. Perceived ability to work was
      not significantly associated with age, gender or work positions. According to
      logistic regression, reduced work performance was significantly positively
      associated with continuous pain [odds ratio (OR) 4.38; 95% CI 1.21-15.7], level
      of perceived pain severity (OR 1.30; 95% CI 1.04-1.63), and health stress (OR
      2.08; 95% CI 1.22-3.54). The results of this study indicated an association
      between specific self-reported stress regarding health and work issues, pain and
      work performance. From a preventive perspective this indicates a need for
      increased awareness about these associations on not only individual level but
      also at the organizational level and in health care.

PMID- 15265208
TI  - Craniomandibular pain, oral parafunctions, and psychological stress in a
      longitudinal case study.
AB  - In a single case study, the most frequently suggested contributing factors to
      craniomandibular pain, viz., oral parafunctions and psychological stress, were
      studied in more detail. During a 13-week study period, questionnaires were
      completed, in which, among others, jaw muscle pain, bruxism behaviour, and
      experienced/anticipated stress were noted. During about 40% of the nights,
      nocturnal masticatory muscle activity (NMMA) was recorded, using single-channel
      electromyography (EMG). The number of NMMA events per recorded hour was scored,
      using a detection threshold of 10% of the maximum voluntary contraction level.
      This threshold was established in a separate study, in which EMG was compared
      with polysomnography. Stepwise regression analyses indicated, that morning jaw
      muscle pain could be explained by evening jaw muscle pain for 64% and by alcohol
      intake for another 2%. In turn, evening jaw muscle pain was explained by daytime
      clenching for 56% and by vacuum sucking of the tongue for an additional 6%.
      Finally, daytime clenching was significantly explained by experienced stress for
      30%. Data of the recorded nights showed, that variations in NMMA did not
      contribute to variations in morning jaw muscle pain. This case study corroborates
      the paradigm that experienced stress may be related to daytime clenching and, in
      turn, to evening and morning jaw muscle pain.

PMID- 15265209
TI  - Association of dietary habits with symptoms of temporomandibular disorders in
      Bangladeshi adolescents.
AB  - The prevalences of signs and symptoms of temporomandibular disorder (TMD) in
      Bangladeshi adolescents and their associations with intake of various hard food
      items were investigated. A group of 1200 randomly selected high school students
      aged 12-17 years from three communities (rural, semi-urban and urban) completed a
      questionnaire on dietary habits and presence of TMD symptoms and were examined
      clinically. In bivariate analysis, no significant relationship was observed
      between TMD symptoms and eating of hard foods. However, in logistic regression
      analysis, clicking showed a significant correlation with consumption of hard
      vegetable and fruits more than three times per week (P < 0.05). A statistically
      significant correlation was also observed between consumption of all hard food
      items (at least one item in each of the four categories of hard food) more than
      12 times per week and pain in the temporomandibular joint (TMJ) (P < 0.05). A
      positive association was found between pain in the TMJ and older age (15-17
      years) (P < 0.001). The prevalence of pain in the TMJ was significantly higher in
      males (P < 0.01). Prevalences of clicking and pain in the TMJ were significantly
      higher in subjects living in a rural area than in subjects living in an urban
      area (P < 0.01 and P < 0.01, respectively). Subjects having one or more decayed,
      missing and filled teeth (DMFT) showed significantly higher prevalences of
      clicking (P < 0.01) and restricted mouth opening (P < 0.01). The results suggest
      that prevalence of TMD symptoms are related to prolonged consumption of hard food
      items.

PMID- 15265210
TI  - Relationship between the TMJ disc and condyle position on MRI and occlusal
      contacts on lateral excursions in TMD patients.
AB  - Confusion about the relationship between dental occlusion and the
      temporomandibular disorders (TMD) has been evident in the literature for many
      years. Previous studies have supported the concept of a multifactorial aetiology
      of TMD, the occlusal factor in general being of minor importance. The purpose of
      the study was to investigate the relationship between condyle and disc positions
      and occlusal contacts on lateral excursions of the mandible in patients with TMD.
      A total of 122 temporomandibular joints (TMJs) of 61 patients with TMD were
      evaluated using magnetic resonance imaging (MRI) and occlusal analyses were made
      clinically. Non-working-side contacts were found to be statistically significant
      in TMJ anterior disc displacement. No significant statistical correlation was
      found between the severity of anterior disc displacement and non-working-side
      contacts in both canine guidance and group function occlusions. There was no
      correlation between non-working-side contacts and condyle positions in both
      occlusion types in the present study. It was concluded that non-working-side
      contacts had some effect on disc position in TMD, however the presence of these
      contacts in both canine guidance and group function occlusions did not correlate
      with anterior disc displacement in TMD statistically. Therefore, non-working-side
      contacts are not to be regarded as the prime cause of anterior disc displacement.

PMID- 15265211
TI  - Impact of posterior occlusal support on the condylar position.
AB  - The purpose of this study was to investigate condylar displacement related to the
      loss of posterior occlusal support. Each of 23 subjects received one occlusal
      adjusted splint that covered all teeth from the right to the left second
      mandibular molar. None of the subjects had a third molar and none of them had a
      missing tooth or showed tooth mobility. The splint was inserted and vertical and
      horizontal condylar position was measured by an ultrasonic motion analyser. The
      splint was then unilateraly shortened tooth-by-tooth up to the canine tooth and
      the measurement was repeated after each shortening. Cutting off the splint's
      second molar on one side lead to a slight ipsilateral cranial motion of the
      condyle if subjects clenched with maximum voluntary force. If the second and
      first molar were cut off, a noticeable cranial condylar movement of about 0.3 mm
      was observed even when teeth occluded with low force. These results suggest that
      loss of posterior occlusal support as it happens in routine oral rehabilitation
      leads to a noticeable cranial condyle movement during registration, even if the
      clenching force is low.

PMID- 15265212
TI  - Pulp size in molars: underestimation on radiographs.
AB  - The aim was to determine whether radiographs provide a clinically useful
      indication of pulp size in diseased/restored human first molar teeth, and to
      investigate accessibility of pulp tissue for diagnostic testing using laser
      Doppler flowmetry (LDF). Extracted teeth of known age were collected. Restorative
      materials were removed and teeth with evidence of pulp exposures excluded. Fifty
      six teeth were radiographed from buccal and mesial aspects, and then their crowns
      were sectioned axiobuccolingually and photographed. Images were digitally scanned
      and measurements made of the total pulp area (above a line across the most
      superior part of the pulpal floor) and the pulp area in the clinical crown
      (superior to a line between the amelocemental junctions). The pulp width at the
      cervix and the highest point of the pulp were also recorded. Data were analysed
      using Pearson correlations. Pulp areas within the clinical crowns were
      significantly larger than indicated by radiographs, by 23% in the case of the
      clinically attainable buccal view (P < 0.05). Pulps may be more accessible to
      flowmeter testing than they appear. Absence of pulp tissues in the crown was
      recorded in equal numbers of teeth on radiographs and sections, but with
      agreement for only one tooth. Sixteen per cent of the teeth had no pulp area in
      the clinical crown when sectioned, but might still be suitable for testing using
      LDF.

PMID- 15265213
TI  - Effectiveness of two-liquid silane primers on bonding sintered feldspathic
      porcelain with a dual-cured composite luting agent.
AB  - The purpose of the current study was to evaluate the effect of two-component
      ceramic primers on the bond strength of a composite material joined to a sintered
      porcelain material. Two sizes of porcelain discs (VMK 68; 10 and 8 mm in diameter
      by 2.5 mm thick) were ground (No. 1000 SiC), and surface-conditioned using one of
      the following systems: (i) unprimed, (ii) Liquid A of the Porcelain Liner M
      material (PLM-A), (iii) Liquid B of Porcelain Liner M (PLM-B), (iv) Liquids A and
      B of Porcelain Liner M (PLM-AB), (v) Liquid A of the Tokuso Ceramics Primer
      material (TCP-A), (vi) Liquid B of Tokuso Ceramics Primer (TCP-B) and (vii)
      Liquids A and B of Tokuso Ceramics Primer (TCP-AB). All specimens were bonded
      with the Bistite II dual-cured composite luting agent, and shear bond strengths
      were determined both after 24 h immersion in water and after subsequent
      thermocycling (4-60 degrees C, 1 min each, 20,000 cycles). Of the seven groups
      assessed, two groups (PLM-AB and TCP-AB) showed the greatest bond strength both
      before (30.7 MPa for PLM-AB and 29.7 MPa for TCP-AB) and after (19.7 MPa for PLM
      AB and 22.4 MPa for TCP-AB) thermocycling (P < 0.05). No significant differences
      were found between the PLM-AB and TCP-AB groups regardless of the application of
      thermocycling (P > 0.05). It can be concluded that both of the acid-catalysed two
      liquid ceramic primers showed superior bonding to the unhydrolysed single-liquid
      silane agents (PLM-B and TCP-A) when the feldspathic porcelain was bonded with
      the Bistite II luting composite.

PMID- 15265214
TI  - The effect of Goldbonder on the adhesion between porcelain and pure titanium.
AB  - The present study examines the effect of a Goldbonder on the adhesion between
      titanium and porcelain as measured by the strain energy release rate (G)
      associated with the interfacial fracture of porcelain and titanium. The influence
      of surface treatment of titanium prior to Goldbonder application was also
      examined. The porcelain side of the specimens was notched to the interface with a
      thin diamond saw, and then a pre-crack was made at the metal-porcelain interface
      by a special jig. The samples were subjected to a four-point bending test
      resulting in stable crack extension from which G was calculated. Both the cracked
      cross-section of interface and peeled fracture surface were examined with
      scanning electron microscope (SEM). The mean G values were 81.57 +/- 10.34, 46.01
      +/- 14.83, and 15.98 +/- 1.76 J m(-2) for the sandblasted surface with the
      Goldbonder, polished surface with the Goldbonder, and sandblasted surface with
      the Pastebonder, respectively. The G values revealed significant differences (P <
      0.01) between Goldbonder and Pastebonder, and between the sandblasted and
      polished surfaces with Goldbonder. The SEM photographs and elemental analysis
      showed that Goldbonder developed both chemical and mechanical bonding to titanium
      and porcelain.

PMID- 15265215
TI  - Bonding between resin luting cement and glass infiltrated alumina-reinforced
      ceramics with silane coupling agent.
AB  - The purpose of this study was to evaluate the shear bond strengths of three dual
      cured resin luting cements (Linkmax HV, Panavia Fluoro Cement, and RelyX ARC) to
      glass-infiltrated alumina-reinforced ceramic material and the effect of four
      silane coupling agents (Clearfil Porcelain Bond, GC Ceramic Primer, Porcelain
      LinerM, and Tokuso Ceramic Primer) on the bond strength. The two type-shaped of
      In-Ceram alumina ceramic glass-infiltrated specimens were untreated or treated
      with one of the four ceramic primers and then cemented together with one of the
      three dual-cured resin luting cements. Half of the specimens were stored in water
      at 37 degrees C for 24 h and the other half thermocycled 20,000 times before
      shear bond strength testing. Surface treatment by all silane coupling agents
      improved the shear bond strength compared with non-treatment. The specimens
      treated with Clearfil Porcelain Bond showed significantly greater shear bond
      strength than any of the other three silane coupling agents regardless of resin
      luting cements and thermocycling except for the use of Panavia Fluoro Cement at
      20,000 thermocycles. When the alumina-reinforced ceramic material was treated
      with any silane coupling agent except GC Ceramic Primer and cemented with Linkmax
      HV, no significant differences in bond strength were noted between after water
      storage and after 20,000 thermocycles. After 20,000 thermocycles, all specimens
      except for the combined use of Clearfil Porcelain Bond or GC Ceramic Primer and
      Linkmax HV and GC Ceramic Primer and Panavia Fluoro Cement showed adhesive
      failures at the ceramic-resin luting cement interface.

PMID- 15265216
TI  - Effect of various surface treatment methods on the bond strength of the heat
      pressed ceramic samples.
AB  - This in vitro study was conducted to evaluate the interaction between the shear
      bond strength and the surface treatment method for a commercial dental ceramic.
      Ninety bonded ceramic units were manufactured for this study. Each unit was made
      by luting two cylinder-shaped ceramic samples to each other with a resin
      composite luting agent. The units were then divided into nine groups, containing
      10 units in each group. Samples from each group were treated with one of the
      following: etching with 4.9% hydrofluoric acid for 10, 20 and 40 s, 9.5%
      hydrofluoric acid for 10, 20 and 40 s, 40% orthophosphoric acid for 40 s, air
      abrasion with alumina in 50-microm particles, and grinding with a high-speed
      diamond bur. The treated samples were then silanated and luted with a resin
      composite luting agent. The luted units were then loaded to failure. Two samples
      from each group were neither silanated nor luted after the surface treatment
      procedure, and morphological changes obtained by various surface treatment
      regimens were investigated by scanning electron microscopy. A statistically
      significant difference was observed among the mean shear bond strengths of the
      groups prepared with different surface treatment techniques (P = 0.00).
      Hydrofluoric acid appeared to be the most suitable chemical medium to produce a
      reliable ceramic bond. Etching time and concentration of the acidic medium were
      also observed as important prognostic variates. Orthophosphoric acid treatment
      was observed to be the least effective surface treatment method on the heat
      pressed ceramic samples. Physical applications such as bur grinding and air
      blasting maintained stronger bonds than the orthophosphoric acid, while producing
      weaker bonds than surfaces treated with hydrofluoric acid in all concentrations
      and etching periods. The effect of the silane priming agent was not considered in
      this study.

PMID- 15265217
TI  - Shear bond strength of microwaveable acrylic resin for denture repair.
AB  - Microwaveable acrylic denture resins are believed to provide an effective means
      of repairing fractured dentures. This in vitro investigation compared the bond
      strength of a microwaveable acrylic resin as a denture repair material to two
      established auto-polymerized resins. Fifty-one specimens were made using Lucitone
      199 as a simulated denture base, and were then divided into three groups of 17
      samples each. Each test group was bonded with the following acrylic resins: Acron
      Mc, Rapid Repair and Palapress. A shear bond strength test was carried out 24 h
      after the samples were bonded. Fracture analysis showed that bond failure was
      adhesive for all groups. Shear bond values showed a statistically significant
      difference at P < 0.05 level between Acron Mc and Rapid Repair; Palapress and
      Rapid Repair, and indicated that Acron Mc and Palapress were superior to Rapid
      Repair as a repair material. However, there was no statistical difference found
      between Acron Mc and Palapress. Microwaveable acrylic resins produce repaired
      junctions of adequate strength.

PMID- 15265218
TI  - Effect of plasma arc curing on polymerization shrinkage of orthodontic adhesive
      resins.
AB  - The purpose of this study was to evaluate the polymerization shrinkage of three
      orthodontic adhesive resins when polymerized with a high-energy plasma arc light
      (1340 mW cm(-2)) and a conventional halogen light (500 mW cm(-2)), and to
      correlate the polymerization shrinkage with the degree of conversion. To equalize
      the total light energy delivered to the adhesive resin, irradiation time was
      varied between 3 or 6 s for a plasma arc-curing unit, and 8 or 16 s for a halogen
      light-curing unit. The polymerization shrinkage of adhesive resins during the
      light-curing process was measured using a computer-controlled mercury dilatometer
      and the degree of conversion was measured using Fourier transform infrared
      spectroscopy. A plasma arccuring unit produced significantly lower polymerization
      shrinkage than a halogen light-curing unit when the equivalent total light energy
      was irradiated to the orthodontic adhesive resins (P < 0.05). The magnitude of
      polymerization shrinkage was significantly different depending on the kind of
      adhesive resins (P < 0.05), but there was no significant correlation between the
      filler fraction and the polymerization shrinkage (r2 = 0.039). There was strong
      correlation (r2 = 0.787) between the polymerization shrinkage and the degree of
      conversion with a halogen light-curing unit, but poor correlation (r2 = 0.377)
      was observed with a plasma arc-curing unit.

PMID- 15265220
TI  - Translucency of glass-fibre-reinforced composite materials.
AB  - summary The purpose of this study was to examine the translucency of glass-fibre
      reinforced composite framework materials. Vectris and FibreKor, as well as an
      experimental material, were the glass-fibre-reinforced framework materials used.
      Targis, Sculpture and Estenia were the types of particulate filler composites
      veneered onto frameworks. Specimens were fabricated from each material, 0.5 and
      1.0 mm thick. In addition, laminate specimens, 1.5 mm thick, were fabricated. The
      translucency of each specimen was evaluated by determining its contrast ratio.
      The laminate specimens were examined for colour differences. The experimental
      framework material was more translucent than the enamel composite when it was not
      coloured, and was nearly as translucent as the dentine composite when coloured.
      The commercial tooth-coloured framework materials were nearly as translucent as
      the dentine composite. It was found that it was possible to reproduce the same
      colour as the veneering dentine composite, when the framework thickness was 0.5
      mm, except in the case of FibreKor. Within the limitations of this study, tooth
      coloured, glass-fibre-reinforced framework materials are nearly as translucent as
      the veneering dentine composite, but these materials affect the colour of the
      prosthesis if the thickness of the framework material is increased beyond a
      certain point.

PMID- 15265223
TI  - The shortage of nurses: is it 'man'-made?

PMID- 15265221
TI  - Effectiveness of wet and dry mercury vapour suppressant systems in a faculty of
      dentistry clinic.
AB  - The objective of this study was to determine the effectiveness of a liquid and a
      dry commercial mercury vapour suppressant system. Measurements were made in a
      student dental clinic, using a mercury vapour detector for periods up to 76
      weeks. The two products examined were Mercon vap liquid in a stock jar and the
      Mercon tainer dry jar system. Amalgam scrap jars were removed from the study when
      the mercury vapour concentration in the jars exceeded the arbitrary cut-off
      criterion of 0.05 mg Hg m(-3). Results showed that the mercury vapour
      concentration in the liquid system exceeded the cut-off criterion in 44 weeks or
      less, whereas the dry system remained below the detection limit (0.01 mg Hg m(
      3)) for the maximum measurement period of 76 weeks. It was concluded that the dry
      system is more effective and reliable than the liquid system. The reliability of
      the liquid system may be influenced by contact of amalgam scrap with the portion
      of the inner wall of the jar that is not covered by liquid. It is proposed that
      amalgam scrap contaminates the wall with mercury during its insertion.

PMID- 15265219
TI  - Effect of traditional and alternative intracoronal bleaching agents on
      microhardness of human dentine.
AB  - The purpose of this study was to compare the effect of traditional and
      alternative bleaching agents on microhardness of human dentine when used
      intracoronally. Thirty-six premolars were divided into six groups and bleaching
      agents were sealed into the pulp chambers as follows: group 1--distilled water
      (control), group 2--30% hydrogen peroxide solution, group 3--sodium perborate
      mixed with distilled water, group 4--sodium perborate mixed with 30% hydrogen
      peroxide solution, group 5--35% carbamide peroxide gel, group 6--35% hydrogen
      peroxide gel. Access cavities were sealed and the teeth were stored in distilled
      water at 37 degrees C. After 7 days, each tooth was sectioned at the cemento
      enamel junction level and microhardness testing was carried out on dentine. The
      results showed that treatment with 35% hydrogen peroxide gel, 30% hydrogen
      peroxide solution and 35% carbamide peroxide gel reduced the microhardness of
      outer dentine to a small extent while treatment with sodium perborate mixed with
      water and sodium perborate mixed with 30% hydrogen peroxide solution did not
      significantly alter the microhardness of dentine.

PMID- 15265224
TI  - Journeying to professionalism: the case of Irish nursing and midwifery research.
AB  - This paper gives a 'discursive' account of the contemporary development of
      nursing and midwifery research in the Republic of Ireland in the context of
      advancing professionalism. Initially, the paper views the landscape by placing
      research in the current framework of Irish nursing and midwifery. It then
      examines the map of our present location by documenting a baseline. It ascertains
      the signposts that are in place by exploring the strategic direction for
      development. Finally, it uses the compass to orienteer the route through the
      various obstacles by examining the challenges of the role of the joint appointee
      leading the implementation of the national Research Strategy for Nursing and
      Midwifery in Ireland.

PMID- 15265225
TI  - Giving voice to the burden of blame: a feminist study of mothers' experiences of
      mother blaming.
AB  - Mother blaming has been identified as a pervasive and serious problem and it is
      known that the professional literature has strong and entrenched mother-blaming
      messages. Using a feminist approach, this paper explores mother blaming as it has
      been experienced by a group of mothers themselves. Analysis of narrative exposes
      mother blaming as a burden that complicates the already-complex responsibilities
      that comprise mothering. Health providers are among those identified by women as
      being particularly likely to attribute problems with (even grown) children to
      maternal fault. Implications for practice and research are drawn from the
      findings of this paper.

PMID- 15265226
TI  - Ethics in nursing homes: experience and casuistry.
AB  - The purpose of the study was to further explore the methods that nurses use to
      solve ethically difficult care situations in nursing homes while the aim of this
      article was to present a model for nursing practice in such situations. Fourteen
      nurses from three nursing homes in Norway were observed and interviewed in order
      to discern the strategies they used to deal with ethically difficult care
      situations. To analyse this information, we used a constant comparative method
      until a grounded theory emerged. The nurses' principal strategy was to apply
      earlier experiences while striving for the best outcome for the elderly patients.
      This article discusses this strategy and compares it to a theory of ethics called
      casuistry. We suggest that by using the method of experiences combined with
      casuistry in a more systematic way, nurses can develop acceptable solutions for
      difficult care situations in nursing homes.

PMID- 15265227
TI  - A nursing intervention for the quality use of medicines by elderly community
      clients.
AB  - Although considerable research and development work has been undertaken on the
      role of General Practitioners (GPs) and pharmacists in medication management,
      monitoring and referral, there is limited research into a role in medication
      management for community nurses. One hundred and thirteen older people living at
      home and receiving community nursing care were assessed for their knowledge of,
      and ability to manage their medication regimen. From these data, a nurse
      initiated intervention was developed that included nursing interventions and
      referral pathways to GPs for people who might benefit from a GP and/or pharmacist
      medication review. A subgroup of 24 participants with diminished knowledge of
      medications or ability to manage their regime (considered to be at risk of drug
      related problems) who were followed up, demonstrated an increase in knowledge,
      some alteration in compliance aids and with no statistically significant change
      in medication regime complexity. This paper details an approach to medication
      review and intervention suitable for community nurses that includes referral
      pathways within the medication team.

PMID- 15265228
TI  - The effectiveness of a pram-walking exercise programme in reducing depressive
      symptomatology for postnatal women.
AB  - The purpose of the research project was to examine the effects of exercise,
      social support and depression on postnatal women who reported experiencing
      postnatal depression. A 12-week randomized, controlled trial was conducted
      investigating the effects of an exercise intervention group (a pram-walking
      programme for mothers and their babies ) compared to a social support group (non
      structured sessions, similar to a playgroup). Participants in both groups had
      given birth in the past 12 months. Pretest data of physical fitness and
      structured questionnaires were compared to post-test effects. The primary
      outcomes were to reduce the depressive symptomatology and improve fitness levels
      of participants in the pram-walking group. Secondary outcomes were to improve the
      social support levels of the participants in both groups and explore women's
      views about the programmes. It was hypothesized that the pram-walking group
      participants would improve their feelings of depression and fitness levels
      compared to the social support group, but that both groups would improve their
      perceived levels of social support. The results showed that mothers in the pram
      walking intervention group improved their fitness levels and reduced their level
      of depressive symptomatology significantly more than the social support group.
      There were no significant changes to social support levels for both groups.
      Therefore, a direct association between improvement in fitness was related to
      improvement in depression for the pram-walking group. However, it is also
      suggested that other factors in combination with improvements in fitness
      influenced improvements in depression levels. It is recommended that pram-walking
      programmes for mothers with postnatal depression be implemented as pilot research
      into existing available services.

PMID- 15265230
TI  - Rofecoxib for dysmenorrhoea: meta-analysis using individual patient data.
AB  - BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy
      and adverse effects of single-dose rofecoxib in primary dysmenorrhoea. METHODS:
      Individual patient information was available from three randomised, double blind,
      placebo and active controlled trials of rofecoxib. Data were combined through
      meta-analysis. Number-needed-to-treat (NNT) for at least 50% pain relief and the
      proportion of patients who had taken rescue medication over 12 hours were
      calculated. Information was collected on adverse effects. RESULTS: For single
      dose rofecoxib 50 mg compared with placebo, the NNTs (with 95% CI) for at least
      50% pain relief were 3.2 (2.4 to 4.5) at six, 3.1 (2.4 to 9.0) at eight, and 3.7
      (2.8 to 5.6) at 12 hours. For naproxen sodium 550 mg they were 3.1 (2.4 to 4.4)
      at six, 3.0 (2.3 to 4.2) at eight, and 3.8 (2.7 to 6.1) at 12 hours. The
      proportion of patients who needed rescue medication within 12 hours was 27% with
      rofecoxib 50 mg, 29% with naproxen sodium 550 mg, and 50% with placebo. In the
      single-dose trial, the proportion of patients reporting any adverse effect was 8%
      (4/49) with rofecoxib 50 mg, 12% (6/49) with ibuprofen 400 mg, and 6% (3/49) with
      placebo. In the other two multiple dose trials, the proportion of patients
      reporting any adverse effect was 23% (42/179) with rofecoxib 50 mg, 24% (45/181)
      with naproxen sodium 550 mg, and 18% (33/178) with placebo. CONCLUSIONS: Single
      dose rofecoxib 50 mg provided similar pain relief to naproxen sodium 550 mg over
      12 hours. The duration of analgesia with rofecoxib 50 mg was similar to that of
      naproxen sodium 550 mg. Adverse effects were uncommon suggesting safety in short
      term use of rofecoxib and naproxen sodium. Future research should include
      restriction on daily life and absence from work or school as outcomes.

PMID- 15265231
TI  - Smoking cigarettes of low nicotine yield does not reduce nicotine intake as
      expected: a study of nicotine dependency in Japanese males.
AB  - BACKGROUND: Many Japanese believe that low-yield cigarettes are less hazardous
      than regular cigarettes, and many smokers consume low-yield cigarettes to reduce
      their risks from smoking. We evaluate the association between actual nicotine
      intake and brand nicotine yield, and the influence of nicotine dependence on this
      association. METHODS: The study subjects included 458 Japanese male smokers, aged
      51.2 +/- 9.9 years, who participated in health check-ups in a hospital in 1998
      and 2000. Each subject filled out a self-administered smoking questionnaire and
      the score of each on the Fagerstrom Test for Nicotine Dependence was calculated.
      Urinary cotinine concentration was measured at the time of participation.
      RESULTS: The geometric mean of urinary cotinine concentration was 535 ng/mgCr for
      those who smoked brands with the lowest nicotine (0.1 mg on the package),
      compared with 1010 ng/mgCr for those who smoked brands with the highest (0.9-2.4
      mg, weighted mean of 1.1 mg). Thus, despite the 11-fold ratio of nicotine yield
      on the packages, the ratio of urinary cotinine level was less than twofold. Both
      nicotine yield on the package and nicotine dependence significantly increased
      urinary cotinine concentration, and the negative interaction between them almost
      attained statistical significance. Cotinine concentration in heavily dependent
      smokers was consistently high regardless of the nicotine yield of brands.
      CONCLUSIONS: The nicotine yield of cigarettes measured by machine-smoking does
      not reliably predict the exposure of smokers. Smokers consuming low-yield
      nicotine cigarettes did not reduce actual intake of nicotine to the level that
      might be expected, especially for those heavily dependent on nicotine. Current
      labeling practices are misleading for the two-third of smokers who are moderately
      or highly dependent on nicotine.

PMID- 15265232
TI  - Identification of astrocytoma associated genes including cell surface markers.
AB  - BACKGROUND: Despite intense effort the treatment options for the invasive
      astrocytic tumors are still limited to surgery and radiation therapy, with
      chemotherapy showing little or no increase in survival. The generation of Serial
      Analysis of Gene Expression (SAGE) profiles is expected to aid in the
      identification of astrocytoma-associated genes and highly expressed cell surface
      genes as molecular therapeutic targets. SAGE tag counts can be easily added to
      public expression databases and quickly disseminated to research efforts
      worldwide. METHODS: We generated and analyzed the SAGE transcription profiles of
      25 primary grade II, III and IV astrocytomas 1. These profiles were produced as
      part of the Cancer Genome Anatomy Project's SAGE Genie 2, and were used in an in
      silico search for candidate therapeutic targets by comparing astrocytoma to
      normal brain transcription. Real-time PCR and immunohistochemistry were used for
      the validation of selected candidate target genes in 2 independent sets of
      primary tumors. RESULTS: A restricted set of tumor-associated genes was
      identified for each grade that included genes not previously associated with
      astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high
      percentage of cell surface genes. Two genes with available antibodies, Aquaporin
      1 and Topoisomerase 2A, showed protein expression consistent with transcript
      level predictions. CONCLUSIONS: This survey of transcription in malignant and
      normal brain tissues reveals a small subset of human genes that are activated in
      malignant astrocytomas. In addition to providing insights into pathway biology,
      we have revealed and quantified expression for a significant portion of cell
      surface and extra-cellular astrocytoma genes.

PMID- 15265233
TI  - Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly
      FOLFIRI regimen for first-line therapy of metastatic colorectal cancer.
AB  - BACKGROUND: Combination therapy of irinotecan, folinic acid (FA) and 5
      fluorouracil (5-FU) has been proven to be highly effective for the treatment of
      metastatic colorectal cancer. However, in light of safety and efficacy concerns,
      the best combination regimen for first-line therapy still needs to be defined.
      The current study reports on the bimonthly FOLFIRI protocol consisting of
      irinotecan with continuous FA/5-FU in five German outpatient clinics, with
      emphasis on the safety and efficiency, quality of life, management of delayed
      diarrhea, and secondary resection of regressive liver metastases. METHODS: A
      total of 35 patients were treated for metastatic colorectal cancer. All patients
      received first-line treatment according to the FOLFIRI regimen, consisting of
      irinotecan (180 mg/m2), L-FA (200 mg/m2) and 5-FU bolus (400 mg/m2) on day 1,
      followed by a 46-h continuous infusion 5-FU (2400 mg/m2). One cycle contained
      three fortnightly administrations. Staging was performed after 2 cycles. Dosage
      was reduced at any time if toxicity NCI CTC grade III/IV was observed.
      Chemotherapy was administered only to diarrhea-free patients. RESULTS: The
      FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51
      of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade
      III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia
      (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4
      CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection
      of liver metastases was achieved in three patients. In one patient, the CR was
      confirmed pathologically. Median progression-free and overall survival were seven
      and 17 months, respectively. CONCLUSIONS: The FOLFIRI regimen proved to be safe
      and efficient. Outpatient treatment was well tolerated. Since downstaging was
      possible, combinations of irinotecan and continuous FA/5-FU should further be
      investigated in neoadjuvant protocols.

PMID- 15265234
TI  - Effects of chemokines on proliferation and apoptosis of human mesangial cells.
AB  - BACKGROUND: Proliferation and apoptosis of mesangial cells (MC) are important
      mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as
      well as in renal disease and glomerular regeneration. Expression of chemokines
      and chemokine receptors by intrinsic renal cells, e.g. SLC/CCL21 on podocytes and
      CCR7 on MC is suggested to play a pivotal role during these processes. Therefore
      the effect of selected chemokines on MC proliferation and apoptosis was studied.
      METHODS: Proliferation assays, cell death assays including cell cycle analysis,
      hoechst stain and measurement of caspase-3 activity were performed. RESULTS: A
      dose-dependent, mesangioproliferative effect of the chemokine SLC/CCL21, which is
      constitutively expressed on human podocytes was seen via activation of the
      chemokine receptor CCR7, which is constitutively expressed on MC. In addition, in
      cultured MC SLC/CCL21 had a protective effect on cell survival in Fas-mediated
      apoptosis. The CXCR3 ligands IP-10/CXCL10 and Mig/CXCL9 revealed a
      proproliferative effect but did not influence apoptosis of MC. Both the CCR1
      ligand RANTES/CCL5 and the amino-terminally modified RANTES analogue Met-RANTES
      which blocks CCR1 signalling had no effect on proliferation and apoptosis.
      CONCLUSIONS: The different effects of chemokines and their respective receptors
      on proliferation and apoptosis of MC suggest highly regulated, novel biological
      functions of chemokine/chemokine receptor pairs in processes involved in renal
      inflammation, regeneration and glomerular homeostasis.

PMID- 15265235
TI  - Treatment of mechanically-induced vasospasm of the carotid artery in a primate
      using intra-arterial verapamil: a technical case report.
AB  - BACKGROUND: Despite improvements in the safety and efficacy of endovascular
      procedures, considerable morbidity may still be attributed to vasospasm.
      Vasospasm has proven amenable to pharmacological intervention such as nitrates,
      intravenous calcium channel blockers (CCBs), and intra-arterial papaverine,
      particularly in small vessels. However, few studies have focused on medium to
      large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil,
      to treat flow-limiting mechanically-induced spasm of the common carotid artery
      (CCA) in a primate. We believe this to be the first such report of its kind. CASE
      PRESENTATION: As part of a study assessing the placement feasibility and safety
      of a catheter capable of delivering intra-arterial cerebroprotective therapy, a
      female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent
      transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of
      acute spasm. The protocol dictated that the catheter remain in the CCA for 12
      hours. Upon completion of the protocol, arteriography revealed a marked decrease
      in CCA size (mean cross-sectional area reduction = 31.6 +/- 1.9%) localized along
      the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and
      arteriography was performed 10 minutes later. Image analysis at 6 points along
      the CCA revealed a 21.0 +/- 1.7% mean increase in vessel diameter along the
      length of the catheter corresponding to a 46.7 +/- 4.0% mean increase in cross
      sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg
      during the procedure. CONCLUSIONS: Intraluminal CCBs like verapamil may
      constitute an effective endovascular treatment for mechanically-induced vasospasm
      in medium to large-sized vessels such as the CCA.

PMID- 15265236
TI  - A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH2,
      induces protease release from mast cells: role in TNF degradation.
AB  - BACKGROUND: Mast cell (MC)-derived serine proteases have been implicated in a
      variety of inflammatory processes. We have previously shown that rat peritoneal
      MC (PMC) express mRNA for protease activated receptor 2 (PAR-2), a G-coupled
      receptor activated by trypsin-like proteases. Recent evidence also suggests that
      MC-induced inflammation can be mediated through PAR. Therefore, we hypothesized
      that specific PAR-2 agonist peptides (PAR-2ap) induce protease release from PMC.
      RESULTS: Western blot analysis of PMC supernatants revealed that a PAR-2ap, tc
      LIGRLO (10 microM), stimulated the release of rat MC protease (RMCP)-1, RMCP-5
      and carboxypeptidase-A. The release was evident by 20 min but further increased
      up to 8 h. To study the biological effects of protease release we tested
      supernatants from tc-LIGRLO, tc-OLRGIL (inactive control peptide) and antigen
      activated PMC for proteolytic activity by seeding with TNF (150 pg/ml),
      incubating for 8 h at 37 degrees C, and measuring TNF remaining in the
      supernatants. Supernatants from tc-LIGRLO-stimulated PMC degraded 44 % of seeded
      TNF (n = 5). Moreover, this TNF proteolysis was dependent on the concentration of
      tc-LIGRLO used to stimulate PMC, and was significantly inhibited (94 %) by
      soybean trypsin inhibitor. Antigen and tc-OLRGIL induced no significant release
      of such proteolytic activity. CONCLUSIONS: These data indicate that a PAR-2ap
      induces the release of proteases from mast cells, which may degrade extracellular
      cytokines and other substrates thus modulating the inflammatory response.

PMID- 15265237
TI  - Characterization of the GATC regulatory network in E. coli.
AB  - BACKGROUND: The tetranucleotide GATC is methylated in Escherichia. coli by the
      DNA methyltransferase (Dam) and is known to be implicated in numerous cellular
      processes. Mutants lacking Dam are characterized by a pleiotropic phenotype. The
      existence of a GATC regulated network, thought to be involved in cold and oxygen
      shift, had been proposed and its existence has recently been confirmed. The aim
      of this article is to describe the components of the GATC regulated network of E.
      coli in detail and propose a role of this network in the light of an evolutionary
      advantage for the organism. RESULTS: We have classified the genes of the GATC
      network according to the EcoCyc functional classes. Comparisons with all of E.
      coli's genes and the genes involved in the SOS and stress response show that the
      GATC network forms a group apart. The functional classes that characterize the
      network are the Energy metabolism (in particular respiration), Fatty acid/
      Phospholipid metabolism and Nucleotide metabolism. CONCLUSIONS: The network is
      thought to come into play when the cell undergoes coldshock and is likely to
      enter stationary phase.The respiration is almost completely under GATC control
      and according to our hypothesis it will be blocked at the moment of coldshock;
      this might give the cell a selective advantage as it increases its chances for
      survival when entering stationary phase under coldshock. We predict the
      accumulation of formate and possibly succinate, which might increase the cell's
      resistance, in this case to antimicrobial agents, when entering stationary phase.

PMID- 15265238
TI  - Endometrial glands as a source of nutrients, growth factors and cytokines during
      the first trimester of human pregnancy: a morphological and immunohistochemical
      study.
AB  - BACKGROUND: The maternal circulation to the human placenta is not fully
      established until 10-12 weeks of pregnancy. During the first trimester the
      intervillous space is filled by a clear fluid, in part derived from secretions
      from the endometrial glands via openings in the basal plate. The aim was to
      determine the activity of the glands throughout the first trimester, and to
      identify components of the secretions. METHODS: Samples of human decidua basalis
      from 5-14 weeks gestational age were examined by transmission electron microscopy
      and immunohistochemically. An archival collection of placenta-in-situ samples was
      also reviewed. RESULTS: The thickness of the endometrium beneath the implantation
      site reduced from approximately 5 mm at 6 weeks to 1 mm at 14 weeks of gestation.
      The glandular epithelium also transformed from tall columnar cells, packed with
      secretory organelles, to a low cuboidal layer over this period. The lumens of the
      glands were always filled with precipitated secretions, and communications with
      the intervillous space could be traced until at least 10 weeks. The glandular
      epithelium reacted strongly for leukaemia inhibitory factor, vascular endothelial
      growth factor, epidermal growth factor, transforming growth factor beta, alpha
      tocopherol transfer protein, MUC-1 and glycodelin, and weakly for lactoferrin. As
      gestation advanced uterine natural killer cells became closely approximated to
      the basal surface of the epithelium. These cells were also immunopositive for
      epidermal growth factor. CONCLUSIONS: Morphologically the endometrial glands are
      best developed and most active during early human pregnancy. The glands gradually
      regress over the first trimester, but still communicate with the intervillous
      space until at least 10 weeks. Hence, they could provide an important source of
      nutrients, growth factors and cytokines for the feto-placental unit. The
      endometrium may therefore play a greater role in regulating placental growth and
      differentiation post-implantation than previously appreciated.

PMID- 15265239
TI  - Color Doppler imaging of cervicocephalic fibromuscular dysplasia.
AB  - BACKGROUND: Fibromuscular dysplasia (FMD) is a possible cause of stroke,
      especially in middle-aged women. However, only few reports are available on
      ultrasonographic detection and monitoring. METHODS: Among the 15,000 patients who
      underwent color Doppler imaging (CDI) of the cervicocephalic arteries during the
      study period, all cases fulfilling ultrasound criteria of FMD were included into
      the case series. Criteria of FMD were: 1. Segmental string-of-beads pattern, 2.
      Localization in the distal extracranial part of internal carotid artery (ICA) or
      vertebral artery (VA), and 3. (optional): Direct and/or indirect criteria of
      stenosis. RESULTS: CDI detected FMD in 39 vessels (37 ICA and 2 VA segments) of
      21 patients. 16 patients had bilateral manifestation on ICA, one of those also on
      VA, bilaterally. CDI disclosed 4 symptomatic high-grade ICA stenoses, 3 of them
      underwent endovascular treatment. 5 patients with moderate symptomatic ICA
      stenoses got medical treatment. In 6 patients FMD was the most likely cause of
      headache and in one patient FMD was diagnosed as a cause of vertigo. CONCLUSIONS:
      CDI may be used for detection of cervicocephalic FMD. Due to the unfavourable
      localisation of FMD for CDI, the sensitivity of CDI is lower in comparison to
      angiography. However, high-grade FMD stenoses that require invasive treatment can
      be recognized on the basis of indirect hemodynamic criteria.

PMID- 15265240
TI  - Algorithms for optimizing drug therapy.
AB  - BACKGROUND: Drug therapy has become increasingly efficient, with more drugs
      available for treatment of an ever-growing number of conditions. Yet, drug use is
      reported to be sub optimal in several aspects, such as dosage, patient's
      adherence and outcome of therapy. The aim of the current study was to investigate
      the possibility to optimize drug therapy using computer programs, available on
      the Internet. METHODS: One hundred and ten officially endorsed text documents,
      published between 1996 and 2004, containing guidelines for drug therapy in 246
      disorders, were analyzed with regard to information about patient-, disease- and
      drug-related factors and relationships between these factors. This information
      was used to construct algorithms for identifying optimum treatment in each of the
      studied disorders. These algorithms were categorized in order to define as few
      models as possible that still could accommodate the identified factors and the
      relationships between them. The resulting program prototypes were implemented in
      HTML (user interface) and JavaScript (program logic). RESULTS: Three types of
      algorithms were sufficient for the intended purpose. The simplest type is a list
      of factors, each of which implies that the particular patient should or should
      not receive treatment. This is adequate in situations where only one treatment
      exists. The second type, a more elaborate model, is required when treatment can
      by provided using drugs from different pharmacological classes and the selection
      of drug class is dependent on patient characteristics. An easily implemented set
      of if-then statements was able to manage the identified information in such
      instances. The third type was needed in the few situations where the selection
      and dosage of drugs were depending on the degree to which one or more patient
      specific factors were present. In these cases the implementation of an
      established decision model based on fuzzy sets was required. Computer programs
      based on one of these three models could be constructed regarding all but one of
      the studied disorders. The single exception was depression, where reliable
      relationships between patient characteristics, drug classes and outcome of
      therapy remain to be defined. CONCLUSION: Algorithms for optimizing drug therapy
      can, with presumably rare exceptions, be developed for any disorder, using
      standard Internet programming methods.

PMID- 15265241
TI  - Hospitalization rates among patients with community-acquired pneumonia treated
      with telithromycin vs clarithromycin: results from two randomized, double-blind,
      clinical trials.
AB  - AIMS: To compare hospitalization rates among patients with community-acquired
      pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on
      pooled data from two randomized, double-blind, multinational clinical trials.
      PATIENTS AND METHODS: Adult patients with CAP eligible for oral therapy (Study 1,
      n = 448; Study 2, n = 575) received telithromycin 800 mg once daily for 10 (Study
      1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500 mg twice daily
      for 10 days. Frequency of CAP-related hospitalizations, physician
      visits/tests/procedures, and additional respiratory tract infection-related
      antibacterial use, as well as CAP-related length of hospital stay and
      hospitalization costs, were compared by treatment group (intent to treat
      populations) up until the late post-therapy visit (Days 31-36). Study
      investigators blinded to treatment regimen assessed whether hospital admissions
      were CAP related. RESULTS: Despite equivalent clinical efficacy for telithromycin
      vs clarithromycin in the clinically evaluable per-protocol populations (n = 784)
      (88.8% [428/482] vs 90.1% [272/302]--difference: -1.3%; 95% CI: -6.0, 3.4),
      telithromycin treatment for 5, 7, or 10 days was associated with significantly
      fewer CAP-related hospitalizations (p = 0.023) and CAP-related hospital days (p =
      0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital
      days per 100 patients). Accordingly, estimated CAP-related hospitalization costs
      were significantly lower (p = 0.025) for telithromycin recipients (30,231 US
      dollars less per 100 patients). CAP-related hospitalizations, duration of
      hospital stay, and hospitalization costs for 7- to 10-day telithromycin--the
      approved dosing regimen for CAP--were significantly lower (p = 0.023, 0.025, and
      0.025, respectively) than for clarithromycin. CONCLUSIONS: Data from this study
      indicate that telithromycin 800 mg once daily for 5, 7, or 10 days provides an
      effective therapy for patients with CAP, and may be associated with fewer CAP
      related hospitalizations and hospital days than clarithromycin 500 mg twice daily
      for 10 days. Treatment with telithromycin could, therefore, potentially translate
      into cost savings in the management of CAP.

PMID- 15265242
TI  - Safety of botulinum toxin type A: a systematic review and meta-analysis.
AB  - OBJECTIVE: To define quantitatively the safety and tolerability profile of
      botulinum toxin type A (BTX-A) across all common therapeutic indications. The
      review was limited to the evaluation of the safety profile of one preparation of
      BTX-A (BOTOX) because distinct formulations of BTX-A are associated with
      different clinical profiles, requiring separate consideration for an analysis of
      safety. RESEARCH DESIGN AND METHODS: We identified randomized controlled trials
      of BTX-A through searches of the MEDLINE, EMBASE, and Cochrane Controlled Trial
      databases for the years 1966-2003. Studies were double-blind, randomized,
      crossover, or of parallel group design. The search strategy included the terms
      'botulinum toxin', 'therapeutic use', 'randomized controlled trial', 'controlled
      clinical trial', 'randomized clinical trial', and 'placebo controlled trial'.
      Only randomized controlled trials of at least 7 days duration that reported
      adverse events were included in the analysis. MAIN OUTCOME MEASURE: Safety was
      assessed by means of a meta-analysis of the number and frequency of adverse
      events. RESULTS: Thirty-six studies involving 2309 subjects met the inclusion
      criteria. These reported on 1425 subjects receiving BTX-A treatment. No study
      reported any severe adverse events. The meta-analysis of any mild to moderate
      adverse events showed a rate of roughly 25% in the BTX-A-treated group (353/1425
      patients) compared with 15% in the control group (133/884 patients, p < 0.001).
      Focal weakness was the only adverse event that occurred significantly more often
      with BTX-A treatment than control. CONCLUSION: The results of this meta-analysis
      and experience from long-term, open-label investigations demonstrate that the
      formulation of BTX-A evaluated here has a favorable safety and tolerability
      profile across a broad spectrum of therapeutic uses.

PMID- 15265243
TI  - The role of sevelamer in achieving the kidney disease outcomes quality initiative
      (K/DOQI) guidelines for hyperphosphatemia.
AB  - BACKGROUND: End-stage renal disease (ESRD) is a chronic health care problem
      associated with multiple co-morbidities and escalating costs. Disregulation of
      mineral metabolism (principally hyperphosphatemia and hypercalcemia) contributes
      to substantial morbidity and mortality. Accordingly, new and more-aggressive
      Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines from the National
      Kidney Foundation promote lower serum phosphorus (3.5-5.5 mg/dL), lower calcium
      (8.4-9.5 mg/dL), and lower calcium-phosphorus product (< 55 mg(2)/dL(2)) targets.
      REVIEW FINDINGS: Traditional calcium-based and metal-based phosphate binders are
      effective but are associated with side effects and toxicity that limit their use.
      Achieving rigorous K/DOQI goals demands higher therapeutic doses of phosphate
      binders and may require more-aggressive use of calcium-free and metal-free
      phosphate binders. Sevelamer hydrochloride is a calcium- and metal-free polymer
      that binds phosphate effectively without contributing to calcium load or metal
      accumulation. In the Treat-to-Goal trial, sevelamer-treated dialysis patients had
      less progression of coronary and aortic calcification than patients treated with
      calcium-based binders. This offers the potential promise of reducing
      cardiovascular morbidity and mortality. The 800-mg tablet (Renagel) increases the
      daily sevelamer dose while reducing the number of tablets required per meal. Nine
      of the 800-mg tablets per day (3 x 800-mg tablets tid with meals) of sevelamer
      monotherapy have been shown to achieve K/DOQI serum phosphorus and calcium
      phosphorus product targets. CONCLUSION: In summary, this review of the current
      evidence-base concludes that the new, more-aggressive, K/DOQI goals limit the use
      of metal-based and calcium-based phosphate binders. Sevelamer offers the
      advantages of lowering serum phosphorus without the risks of calcium or metal
      accumulation - and offers the promise of slowing the progression of vascular
      calcification and potentially reducing the morbidity and mortality of
      hemodialysis patients.

PMID- 15265244
TI  - Low molecular weight heparins: the optimal treatment for venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common vascular complication that requires
      immediate as well as long-term treatment. Unfractionated heparin (UFH), followed
      by oral anticoagulants (OAs), is of proved efficacy in the treatment of deep
      venous thrombosis (DVT) and pulmonary embolism (PE). However, low molecular
      weight heparins (LMWHs) have successfully replaced UFH both in the prevention and
      in the initial treatment of DVT and PE. Recent trials evaluated the efficacy and
      safety of LMWH therapy as an alternative to vitamin K antagonists in long-term
      VTE secondary prophylaxis for all patients and in specific subgroups. LMWHs
      differ considerably from each other. These agents were studied separately,
      administered according to various protocols, in various doses and for different
      duration of treatment. Results from prospective randomized trials, conducted
      during the last decade, indicate that LMWHs are at least as effective and yet
      safer than OAs in the long-term treatment of VTE. In this brief overview, we
      consider the potential advantages of treatment with LMWH in patients with VTE.

PMID- 15265245
TI  - A dependency model for patients with Alzheimer's disease: its validation and
      relationship to the costs of care--the LASER-AD Study.
AB  - BACKGROUND: Loss of independence becomes more marked as Alzheimer's disease (AD)
      progresses and contributes significantly to its societal and economic burden.
      Existing measures of functional disability focus either on basic or on
      instrumental activities of daily living (ADL). It would be more appropriate to
      combine these but, using existing assessment tools, this would involve
      considerable quantitative analysis. Recently, a qualitative and pragmatic system
      of classifying AD patients according to levels of dependency has been developed
      in a Belgian cohort. OBJECTIVES: To validate independently, in a UK community
      setting, a functional classification model of AD patients and to explore the
      relationship between dependency and costs of care using this model. RESEARCH
      DESIGN AND METHODS: Longitudinal epidemiological study of 224 AD patients. Data
      were collected at baseline and at 6 months on ADL, global state, cognition,
      behavioural dimensions, depression, quality of life and resource utilisation
      using validated instruments. An automatic classification algorithm was performed
      to allow identification of dependency clusters. The scheme was tested for
      validity against other simultaneously collected data including health and social
      care costs. The relationship between dependency and costs of care was explored
      using ANOVA models. RESULTS: Analysis of the ADL assessment instruments produced
      three ADL sub-scores by which patients could be classified into one of three
      disability clusters: ('non-dependent', 'non-dependent with instrumental
      functional disability', and 'dependent'). Good external validity of the
      classification scheme was demonstrated by correlation with simultaneously
      collected data. After a backward selection process on ANOVA model (at a 5%
      level), institutionalisation and the most dependent status were the most
      significant cost drivers. CONCLUSIONS: Qualitative classification of AD patients
      using dependency levels is a simple and validated approach. Applying this
      approach showed that institutionalisation and the most 'dependent' status were
      independently and significantly associated with high care cost.

PMID- 15265246
TI  - Quetiapine in schizophrenia: onset of action within the first week of treatment.
AB  - OBJECTIVE: Three placebo-controlled clinical trials have established the efficacy
      of the atypical antipsychotic quetiapine (Seroquel) in schizophrenia. These
      trials were designed and powered to detect a treatment difference in the primary
      endpoint at Week 6. The objective of the current analysis was to investigate the
      effect of quetiapine at earlier timepoints. RESEARCH DESIGN AND METHODS: A
      combined analysis of data from three acute, double-blind, placebo-controlled,
      randomised trials was carried out. The trials comprised hospitalised patients
      with an acute exacerbation of chronic or subchronic schizophrenia who were
      randomised to receive quetiapine 150-750 mg/day (n = 422) or placebo (n = 198).
      Symptoms were assessed using changes from baseline to Week 1 in the Brief
      Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score
      and the individual BPRS items of excitement, tension and depression. Changes from
      baseline to Weeks 1-6 were calculated for BPRS Factor 1 scores (which measures
      mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary
      scores. RESULTS: Within 1 week, overall symptom improvement (BPRS total score)
      was significantly (p < 0.05) greater with quetiapine than with placebo;
      improvement also occurred in individual BPRS items of excitement, tension and
      depression. Improvement in negative symptoms was significantly (p < 0.05) greater
      with quetiapine than with placebo from Week 1, as was the BPRS Factor I score
      from Week 2. More quetiapine- than placebo-treated patients showed a response of
      positive symptoms to treatment within 1 week (p < 0.05). CONCLUSIONS: The
      beneficial effects of quetiapine are observed within 1 week across a broad
      spectrum of symptoms.

PMID- 15265247
TI  - Statins are less effective in common daily practice among patients with
      hypercholesterolemia: the REALITY-PHARMO study.
AB  - BACKGROUND: To study the use and effectiveness of lipid-lowering drugs with
      respect to lowering of cholesterol levels in routine daily practice. METHODS: 20
      392 patients for whom lipid levels records were available between January 1991
      and December 2001 were included in this retrospective population based cohort
      study. From this group of patients 1899 patients started treatment during the
      study period and had at least one baseline cholesterol measurement during the six
      months prior to the initiation of lipid lowering drugs and at least one
      cholesterol measurement after initiation. A patient was defined to be 'at goal'
      if the patient had a total cholesterol less than 5.0 mmol/L. RESULTS: Our results
      indicate that only 30.2% of all treated patients achieved goal in the first year
      of treatment. After the introduction of new guidelines in 1998, recommending more
      aggressive treatment, the goal attainment percentage rose from 22.4% of those
      patients treated before 1998 to 42.3% for those in whom treatment was initiated
      after 1998. CONCLUSION: The percentage of patients achieving guideline
      recommended goal is low in real-life even in patients treated with high dose
      statins.

PMID- 15265248
TI  - Comment on Disintegration/dissolution profiles of copies of Fosamax
      (alendronate).

PMID- 15265249
TI  - Economic outcomes associated with olanzapine versus risperidone in the treatment
      of uncontrolled schizophrenia.
AB  - OBJECTIVE: This study, based upon a database analysis, compares a one-year drug
      treatment course (duration of therapy, concomitant use of typical antipsychotics,
      anxiolytics/antidepressants or anti-Parkinsonians) and direct health care costs
      of uncontrolled schizophrenia patients initiated on olanzapine versus
      risperidone. METHODS: The integrated medical and pharmacy claims of a large,
      geographically diverse, commercially insured population of 1.6 million employees,
      retirees and dependents were used to conduct this analysis. Patients who
      initiated outpatient treatment with either olanzapine or risperidone (no
      prescription for olanzapine or risperidone during a 1-year period prior to the
      initiation) and with uncontrolled schizophrenia were included. Drug treatment
      course and associated health care costs (calculated based on charges) during the
      subsequent 12-month period were examined using univariate and multivariate
      methods. RESULTS: 431 patients initiated on risperidone and 142 initiated on
      olanzapine met the inclusion criteria. The mean dose was 4.34 and 11.00 mg/day
      for risperidone and olanzapine, respectively. Olanzapine was associated with more
      favorable drug treatment course than risperidone. Although pharmaceutical costs
      were significantly higher, medical costs were significantly lower for patients on
      olanzapine compared to those on risperidone. Univariate and multivariate analyses
      (controlling for potential confounding factors including demographic and clinical
      characteristics) consistently demonstrated that olanzapine patients had
      significantly lower schizophrenia related costs (2839 US dollars less, p <
      0.011), lower mental health care costs (3744 US dollars less, p < 0.004) and
      lower total health care costs (4674 US dollars less, p < 0.001) than those
      patients initiated on risperidone. CONCLUSIONS: The findings revealed significant
      differences between olanzapine and risperidone in the treatment of uncontrolled
      schizophrenia patients in clinical practice. Olanzapine patients experienced a
      favorable drug treatment course and incurred lower overall costs. The lower costs
      were hospital-treatment driven. Further studies are needed to examine if these
      results hold for different patient populations.

PMID- 15265250
TI  - Effect of raloxifene on the incidence of elevated low density lipoprotein (LDL)
      and achievement of LDL target goals in postmenopausal women.
AB  - OBJECTIVE: To determine the extent to which raloxifene can maintain low density
      lipoprotein cholesterol (LDL-C) levels below 160 mg/dL or reduce elevated LDL-C
      levels to below lipid-lowering goals in postmenopausal women. PATIENTS AND
      METHODS: The Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis
      treatment trial randomized 7705 postmenopausal women to placebo or raloxifene (60
      mg or 120 mg) daily for a core treatment phase of 3 years. Changes in LDL-C and
      other serum lipids in a subset of women was a predefined secondary objective.
      This post-hoc analysis included the 2413 women who did not take lipid-lowering
      medications at any time during the trial and for whom LDL-C measurements were
      available. The threshold for high LDL-C (> or = 160 mg/dL) and LDL-C lipid
      lowering goals were defined according to National Cholesterol Education Program
      Adult Treatment Panel III (NCEP-ATP III) guidelines. RESULTS: The percent of
      women with LDL-C < 160 mg/dL was comparable between treatment groups at baseline
      (placebo, 57.5%; raloxifene 60 mg, 56.4%; raloxifene 120 mg, 56.8%). At 3 years,
      the percent of these women whose LDL-C had increased to above 160 mg/dL was
      significantly less in the raloxifene 60 mg and 120 mg groups compared with
      placebo by 65% (95% CI, 44%-78%) and 64% (95% CI, 43%-77%), respectively. Among
      women with elevated (defined for these analyses as > or = 160 mg/dL) LDL-C at
      baseline, the proportion having elevated LDL-C at 3 years was significantly less
      in the raloxifene 60 mg and 120 mg groups compared with placebo by 32% (95% CI,
      24%-40%) and 40% (95% CI, 32%-48%), respectively. Fifty percent and 13% of these
      women achieved LDL-C goals of < 160 mg/dL and < 130 mg/dL, respectively (P <
      0.001 vs. placebo for both) in the raloxifene 60 mg group, with similar results
      for the raloxifene 120 mg group. CONCLUSIONS: In postmenopausal women with
      osteoporosis not taking concurrent lipid-lowering therapy, raloxifene
      significantly reduced the incidence of LDL-C > or = 160 mg/dL and significantly
      increased the proportion achieving LDL-C goals for lipid-lowering compared with
      placebo. Whether these and other effects of raloxifene on cardiovascular risk
      markers will improve cardiovascular outcomes requires further study.

PMID- 15265251
TI  - Nicotinic receptors and schizophrenia.
AB  - The incidence of smoking is very high in non-schizophrenic subjects presenting
      various psychiatric disorders (35 to 54%). However, the incidence of smoking is
      extremely high in schizophrenic patients: 80% to 90%, versus 25% to 30% of the
      general population. Various studies have demonstrated that the use of tobacco
      transiently restores the schizophrenic patient's cognitive and sensory deficits.
      Smoking cessation also appears to exacerbate the symptoms of the disease. Post
      mortem binding studies have revealed a disturbance of nicotinic receptor
      expression, affecting the alpha(7) and alpha(4)beta(2) subunits, in various
      cerebral areas. Genetic linkage studies have also shown that the alpha(7) subunit
      is involved in schizophrenia. This review assesses the involvement of the
      nicotinic system in schizophrenia and suggests ways in which this system may
      participate in the pathophysiology of this disease.

PMID- 15265252
TI  - Efficacy of etanercept delivered by perispinal administration for chronic back
      and/or neck disc-related pain: a study of clinical observations in 143 patients.
AB  - OBJECTIVE: Documentation of the clinical results obtained utilizing perispinal
      etanercept off-label for treatment-refractory back and neck pain in a clinical
      practice setting. RESEARCH DESIGN AND METHODS: The medical charts of all patients
      who were treated with etanercept for back or neck pain at a single private
      medical clinic in 2003 were reviewed retrospectively. Patients were treated if
      they had disc-related pain which was chronic, treatment-refractory, present every
      day for at least 8 h, and of moderate or severe intensity. Patients with active
      infection, demyelinating disease, uncontrolled diabetes, lymphoma or
      immunosuppression were excluded from treatment with etanercept. Etanercept 25 mg
      was administered by subcutaneous injection directly overlying the spine. Visual
      Analogue Scales (VAS, 0-10 cm) for intensity of pain, sensory disturbance, and
      weakness prior to and 20 min, 1 day, 1 week, 2 weeks, and 1 month after treatment
      were completed. Inclusion criteria for analysis required baseline and treatment
      VAS data. MAIN OUTCOME MEASURES: Before and after treatment VAS comparisons for
      intensity of pain, sensory disturbance, and weakness. RESULTS: 143 charts out of
      204 met the inclusion VAS criteria. The 143 patients had a mean age of 55.8 +/-
      14, duration of pain of 9.8 +/- 11 years, and an initial Oswestry Disability
      Index of 42.8 +/- 18, with 83% having back pain, 61% sciatica, and 33% neck pain.
      30% had previous spinal surgery, and 69% had previously received epidural steroid
      injections (mean 3.0 +/- 3). The patients received a mean of 2.3 +/- 0.7 doses of
      perispinal etanercept separated by a mean interval of 13.6 +/- 16.3 days. The
      mean VAS intensity of pain, sensory disturbance, and weakness were significantly
      reduced after perispinal etanercept at 20 min, 1 day, 1 week, 2 weeks, and 1
      month with a p < 0.0001 at each time interval for the first dose in this patient
      population. CONCLUSIONS: Perispinal etanercept is a new treatment modality which
      can lead to significant clinical improvement in selected patients with chronic,
      treatment-refractory disc-related pain. Generalizability of the present study
      results is limited by the open-label, uncontrolled methodology employed. Based on
      this and other accumulating recent studies, etanercept may be useful for both
      acute and chronic disc-related pain. Further study of this new treatment modality
      utilizing double-blind placebo controlled methodology is indicated. NOTE: This
      treatment method is protected by multiple patents awarded to Edward Tobinick MD,
      including U. S. patents 6 015 557; 6 177 077; 6 419 944; 6 537 549 and Australian
      patent 758 523.

PMID- 15265253
TI  - Effectiveness of simvastatin therapy in raising HDL-C in patients with type 2
      diabetes and low HDL-C.
AB  - OBJECTIVE: To evaluate the efficacy of high and moderate doses of simvastatin (80
      and 40 mg), for raising high density lipoprotein-cholesterol (HDL-C), improving
      HDL sub-fractions, and affecting other parameters, including high sensitivity C
      reactive protein (hs-CRP), in patients with type 2 diabetes mellitus (DM) and low
      HDL-C. RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled,
      randomized, 3-period, complete block, 6-week crossover study examined the
      efficacy of simvastatin in adult men and women (N = 151) with stable type 2 DM
      (HbA(1C) < 9%), low density lipoprotein-cholesterol (LDL-C) > 100 mg/dL (2.6
      mmol/L), HDL-C < 40 mg/dL (< 1 mmol/L), and fasting triglyceride level > 150 (>
      1.7 mmol/L) and < 700 mg/dL (< 7.9 mmol/L). This study included adult men (71%)
      and women (29%) of various races (89% white, 6% black, 1% Asian, 3% other)
      enrolled from 29 practice-based sites in the United States. MAIN OUTCOME
      MEASURES: Percentage change in HDL-C from baseline at the end of each 6-week
      treatment interval. RESULTS: Both simvastatin 80 and 40 mg significantly
      increased total HDL-C from baseline (mean increases of 8% +/- 1 [SE] and 5% +/-
      1, respectively; p < 0.001) compared with placebo, and significantly reduced
      plasma concentrations of LDL-C (p < 0.001), triglycerides (p < 0.001),
      apolipoprotein B (p < 0.001), and hs-CRP (p < or = 0.012). Compared with
      simvastatin 40 mg, the 80 mg dose provided additional efficacy. Simvastatin 80 mg
      also significantly (p < 0.001) increased HDL(2) from baseline (14% +/- 3[SE]) and
      placebo phases (10 +/- 3). An exploratory analysis showed 87% (simvastatin 80 mg)
      and 82% (simvastatin 40 mg) of patients reached the NCEP ATP III treatment goals
      for LDL-C compared with 14% on placebo. CONCLUSIONS: Both simvastatin 80 and 40
      mg raise HDL-C and improve other measures associated with elevated coronary risk
      in patients with type 2 DM and low HDL-C.

PMID- 15265254
TI  - Achieving therapeutic targets in renal anaemia: considering cost-efficacy.
AB  - Erythropoietin treatment for anaemia in chronic kidney disease (CKD) brings
      important clinical benefits, but restricted healthcare budgets necessitate value
      for-money therapies, requiring economic considerations also to be taken into
      account when selecting a treatment regimen. Subcutaneous (s.c.) administration of
      epoetin is effective at a lower dose than intravenous (i.v.) administration,
      offering the potential for substantial reductions in costs of treatment. Unlike
      epoetin alfa, which is contra-indicated by the s.c. route in Europe in patients
      with CKD, epoetin beta (NeoRecormon) can be safely and effectively given by
      either route. The multidose presentations of epoetin beta (Reco-Pen, multidose
      vials) may provide further opportunity for dose reduction. The tolerability of
      s.c. epoetin beta is excellent and superior compared with epoetin alfa or
      darbepoetin alfa. Epoetin beta given once weekly is as effective as two- or three
      times weekly, and the dosing frequency can be further reduced to once every 2
      weeks in patients who are stable on once-weekly dosing. Reduced dosing frequency
      is more convenient for the patient and may save nursing time in dialysis units.
      Overall, s.c. epoetin beta, compared with alternative treatments, may represent a
      cost-effective treatment option for anaemia management as it combines a well
      established safety and efficacy record, favourable local tolerability, and the
      convenience of once-weekly dosing with the potential to reduce treatment costs by
      up to 30%.

PMID- 15265255
TI  - Triple nucleoside treatment with abacavir plus the lamivudine/zidovudine
      combination tablet (COM) compared to indinavir/COM in antiretroviral therapy
      naive adults: results of a 48-week open-label, equivalence trial (CNA3014).
AB  - OBJECTIVE: An equivalence (non-inferiority) trial comparing antiviral response,
      tolerability, and adherence with a triple nucleoside regimen containing abacavir
      300 mg (ABC) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet (COM)
      twice daily vs. a regimen containing the protease inhibitor indinavir (IDV) 800
      mg three times daily plus COM twice daily (IDV/COM) in antiretroviral-naive, HIV
      infected patients. METHODS: Adult patients with plasma HIV-1 RNA levels > or =
      5000 copies/mL and CD4+ cell counts > or = 100 cells/mm(3) were randomized to
      receive open-label ABC/COM (n = 169) or IDV/COM (n = 173) for 48 weeks. The
      intent-to-treat (ITT) population was the primary population evaluated. ITT:
      switch/missing equals failure (ITT: S/M = F) and as-treated (AT) analyses were
      used for assessing the proportion of patients achieving plasma HIV-1 RNA level <
      400 and < 50 copies/mL at each clinic visit. In the ITT: S/M = F analysis,
      patients who switched treatment or had missing values were considered treatment
      failures; the AT analysis examined virologic data only while patients received
      study treatment. ABC/COM was considered equivalent (non-inferior) to IDV/COM if
      the lower limit of the 95% confidence intervals (CIs) about the difference in
      proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA <
      400 copies/mL exceeded -15% at week 48. RESULTS: The study population was diverse
      with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4%
      other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80
      log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). ABC/COM met the
      criterion of equivalence to IDV/COM. In the ITT: S/M = F analysis at Week 48, a
      greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL
      (66% [109/164] vs. 50% [82/165]; treatment difference 16.6%, 95% CI (6.0, 27.2),
      p = 0.002) and HIV-1 RNA < 50 copies/mL (60% [99/164] vs. 50% [83/165]; treatment
      difference 9.6%, 95% CI [-1.1, 20.2]), whereas the AT analysis showed similar
      proportions achieving these endpoints (< 400 copies/mL: 85 vs. 83%; < 50
      copies/mL: 79 vs 81%). Comparable proportions of patients with screening HIV-1
      RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL (ABC/COM: 60%
      [35/58]; IDV/COM: 51% [33/65]; treatment difference 9.6%, 95% CI [-7.9, 27.1];
      ITT: S/M = F analysis). A significantly greater proportion taking ABC/COM were >
      or = 95% adherent (72% [109/151] vs. 45% [70/154] with IDV/COM, p < 0.001).
      Median increases from baseline in CD4+ cell counts were similar in the two
      treatment groups (+148 vs. +152 cells/mm(3)). Significantly more patients on
      IDV/COM reported drug-related adverse events (87% [142/165] vs. 65% [108/164]
      with ABC/COM, p < 0.001), similar proportions discontinued treatment due to
      adverse events (13 vs. 10%), and a slightly greater proportion in the ABC/COM
      group reported serious adverse events (13 vs. 8%). About half of the latter
      comprised suspected ABC-related hypersensitivity reactions (overall rate, 6%).
      Most adverse events were gastrointestinal in nature in both treatment groups.
      CONCLUSION: ABC/COM was at least equivalent to IDV/COM over 48 weeks in the
      treatment of antiretroviral-naive patients. ABC/COM was associated with a
      significantly higher adherence rate and lower incidence of drug-related adverse
      events than IDV/COM. The study was limited in that it was not powered to
      determine equivalence of treatments within high vs. low viral load strata,
      adherence was not monitored electronically, and bias could not be ruled out due
      to the open-label study design.

PMID- 15265257
TI  - Identifying patients who require a change in their current acute migraine
      treatment: the Migraine Assessment of Current Therapy (Migraine-ACT)
      questionnaire.
AB  - BACKGROUND: Currently available measures of the efficacy of acute migraine
      medications are not frequently used in primary care. They may be too burdensome
      and complicated for routine use. OBJECTIVES: To design and test a new, easy to
      use, 4-item assessment tool, the Migraine Assessment of Current Therapy (Migraine
      ACT) questionnaire for use by clinicians, to quickly evaluate how a recently
      prescribed acute medication is working, and to identify patients who require a
      change of their current acute treatment. METHODS: A 27-item Migraine-ACT
      questionnaire was developed by an international advisory board of headache
      specialists. Questions were formulated in four domains: headache impact, global
      assessment of relief, consistency of response and emotional response. All these
      are clinically important measures of migraine severity and treatment outcome. All
      questions were dichotomous and answered by yes or no. Patients (n = 185)
      attending secondary care headache clinics who were diagnosed with migraine
      according to International Headache Society criteria entered a multinational,
      prospective, observational study to investigate the test-retest reliability and
      construct validity of the 27-item Migraine-ACT. Patients completed the Migraine
      ACT on two occasions, separated by a 1-week interval, and test-retest reliability
      was assessed by Pearson product moment and Spearman rank measures. Construct
      validity was assessed by correlating patients' answers to the 27-item Migraine
      ACT with those to other questionnaires (individual domains and total scores)
      conceptually related to it; the Short-Form 36 quality of life questionnaire (SF
      36), the Migraine Disability Assessment (MIDAS) questionnaire and the Migraine
      Therapy Assessment Questionnaire (MTAQ). Discriminatory t-tests were used to
      identify the four Migraine-ACT questions (one in each domain) which discriminated
      best between the domains of the SF36, MIDAS, and MTAQ. These four items
      constituted the final 4-item Migraine-ACT. RESULTS: The test-retest reliability
      of the 27 Migraine-ACT questions ranged from good to excellent, and correlation
      coefficients were highly significant for all items. The consistency of reporting
      the yes and no answers was also excellent. Correlations of Migraine-ACT items
      with SF-36 and MIDAS items and SF-36, MIDAS and MTAQ total scores indicated that
      the following were the most discriminating items, in the respective four domains,
      and constitute the final Migraine-ACT questionnaire: Consistency of response:
      Does your migraine medication work consistently, in the majority of your attacks?
      Global assessment of relief: Does the headache pain disappear within 2 h? IMPACT:
      Are you able to function normally within 2 h? Emotional response: Are you
      comfortable enough with your medication to be able to plan your daily activities?
      The 4-item Migraine-ACT was shown to be highly reliable (Spearman/Pearson measure
      r = 0.82). The individual questions, and the total 4-item Migraine-ACT score,
      showed good correlation with items of the SF-36, MIDAS and MTAQ questionnaires,
      particularly with the total MTAQ and SF-36 scores. CONCLUSIONS: The 4-item
      Migraine-ACT questionnaire is an assessment tool for use by primary care
      physicians to identify patients who require a change in their current acute
      migraine treatment. It is brief and simple to complete and score, and has
      demonstrated reliability, accuracy and simplicity. Migraine-ACT can therefore be
      recommended for everyday clinical use by clinicians.

PMID- 15265258
TI  - Risk stratification for the prevention of cardiovascular complications of
      hypertension.
AB  - Arterial hypertension is a well established risk factor for both coronary artery
      disease (CAD) and stroke. The decision to treat hypertension and prevent
      cardiovascular complications has, for many years, been based on the level of
      blood pressure. The present review, based on a cross-sectional and careful
      analysis of major trials, emphasises the need to assess the cardiovascular risk
      for each patient in order to make appropriate treatment decisions. Evaluation of
      cardiovascular risk in untreated hypertensive subjects indicates that coronary
      risk is two to three times higher than cerebrovascular risk. The same results
      have been observed in outcome trials where hypertensive patients were treated
      with antihypertensive drugs. Even though the results of outcome trials for
      antihypertensive drugs can be explained by blood pressure differences between
      randomised groups, antihypertensive drugs are, for the same reduction in blood
      pressure, more efficient in preventing cerebrovascular events than in preventing
      (CAD). Meta-analysis indicates that each reduction of 2 mmHg in systolic blood
      pressure levels is associated with a 25% reduction in stroke events, but a
      difference of at least 5 mmHg for systolic pressure between groups is necessary
      to obtain prevention of coronary events. A number of controlled trials using
      statins have shown that these drugs were particularly effective in preventing
      coronary disease. An appropriate therapeutic strategy for cardiovascular risk
      reduction in hypertensive patients should therefore include both antihypertensive
      therapy and prescription of a statin. The efficacy of this strategy was recently
      reported in the ASCOT trial, which estimated that for 100 hypertensive patients
      with a high cardiovascular risk and followed up for 10 years, the number of
      coronary events is 13, 10 and 7 for those without antihypertensive treatment,
      with antihypertensive therapy only and with both antihypertensive therapy and
      statin therapy, respectively.

PMID- 15265256
TI  - Predictors of adherence and virologic outcome in HIV-infected patients treated
      with abacavir- or indinavir-based triple combination HAART also containing
      lamivudine/zidovudine.
AB  - OBJECTIVES: To compare dosing convenience and adherence with abacavir (ABC) 300
      mg plus a fixed-dose lamivudine 150 mg/zidovudine 300 mg combination tablet (COM)
      twice daily versus indinavir (IDV) plus COM twice daily in treatment-naive, HIV-1
      infected adults; and to evaluate the association among difficulty taking
      antiretroviral regimens, adherence, and virologic efficacy. METHODS: An open
      label, randomized, multicenter, international study compared the COM/ABC and
      IDV/COM regimens with respect to self-reported adherence and regimen convenience
      over 48 weeks. Logistic regression analysis (LRA) was done on a patient sub
      sample from both groups to evaluate predictors of adherence and virologic
      response at last time-point on randomized therapy (LTORT). RESULTS: The study
      population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28%
      white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1
      RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). Of 329
      patients who were randomized and received treatment, 315 (96%) provided adherence
      data. Significantly more patients in the ABC/COM group than in the IDV/COM group
      reported > or = 95% adherence to therapy (76 vs 58%, p < 0.001) and no difficulty
      in taking their regimen (91 vs 61%, p < 0.001). In both groups, the highest
      probability of HIV-1 RNA < 400 copies/mL occurred when median adherence was > or
      = 95%. The probability of HIV-1 RNA < 400 copies/mL declined more rapidly in the
      IDV/COM group as adherence rates decreased. LRA showed that no difficulty taking
      any of the drugs in the regimen, ABC/COM treatment group, and male gender were
      independent significant predictors of > or = 95% adherence (p < 0.05). Median
      adherence and baseline HIV-1 RNA were significant predictors of HIV-1 RNA < 400
      copies/mL (p < 0.05). CONCLUSIONS: Patients reported greater ease of use and
      superior adherence to ABC/COM than IDV/COM. Patient-reported difficulty taking
      drugs in a regimen was predictive of reduced adherence, and both of the latter
      factors were predictive of poorer virologic outcome. Adherence levels of > or =
      95% in both treatment groups maximized the probability of patients achieving an
      HIV-1 RNA < 400 copies/mL.

PMID- 15265259
TI  - Impact of migraine on patients and their families: the Migraine And Zolmitriptan
      Evaluation (MAZE) survey--Phase III.
AB  - OBJECTIVE: To investigate the impact of migraine on migraineurs and their
      families and evaluate migraineurs' preference for different treatment
      formulations. This study also assessed the prevalence and impact of migraine with
      menstruation. METHODS: Participants (n = 1028) from around the world (USA [39%],
      Canada [20%], Europe [37%] and other countries [4%]) completed an online
      questionnaire. Of these, 866 were migraineurs and 162 were non-migraineurs living
      with/related to migraineurs. Migraineurs were identified based on responses to a
      modified Kiel questionnaire and/or diagnosis of migraine by a doctor. Disability
      was quantified using the Migraine Disability Assessment Scale (MIDAS). RESULTS:
      Migraineurs missed more days from family/leisure activities than from work/school
      (mean 4.2 vs 2.4 days) in the previous 3 months. On an additional 6.2 days within
      the 3-month period, productivity at work/school was reduced by at least half.
      Inability and reduced ability (by at least half) to perform household work were
      reported on 6.0 and 6.5 days, respectively. Of the women surveyed, 51% identified
      menstruation as a trigger for attacks and 6% reported attacks solely with
      menstruation (i. e. attacks occurred during menstruation on at least 9 out of 10
      occasions), the latter associated with a higher pain score than other attacks.
      Living with or being related to a migraineur decreased nonmigraineurs' ability to
      participate in home/family life (moderate/great impact 49%) and social/leisure
      activities (moderate/great impact 47%). In a tradeoff analysis, 60% of treatment
      choice was driven by formulation type and 40% was driven by speed of onset. As
      migraine disability increased, speed of onset became more important. CONCLUSIONS:
      This study confirms the significant burden of migraine on patients and
      families/cohabitants, highlighting not only reduced productivity and absences
      from work/school, but also time missed from family/social occasions. Many women
      identify menstruation to be associated with more painful attacks. Overall, in
      terms of treatment choice, formulation type was a more important driver than
      speed of onset; however, as migrainerelated disability escalates, speed of onset
      becomes more important. To optimise migraine management, treatment choice should
      be based on individual patients' needs and preferences.

PMID- 15265260
TI  - Treatment priorities and current prescribing patterns in hypertension: results of
      GRASP, an international physician survey.
AB  - The GRASP (Global Research on Attitudes about hypertension and Stroke Prevention)
      survey, conducted in 11 countries and involving 825 physicians, was designed to
      investigate physician perceptions and priorities in the treatment of hypertension
      and influences on choice of antihypertensive therapy. The prevention of stroke
      was identified as a major priority in this survey, but there appeared to be some
      degree of mismatch between the evidence from large controlled trials and current
      patterns of prescribing for stroke prevention. The results of GRASP confirm the
      desirability of research to identify methods and strategies that will facilitate
      the integration of clinical trial results into general practice treatment of
      hypertension.

PMID- 15265261
TI  - Comment on Putting evidence-based medicine into clinical practice: comparing anti
      resorptive agents for the treatment of osteoporosis.

PMID- 15265263
TI  - Brain hypoperfusion: a critical factor in vascular dementia.
AB  - Subcortical ischemic vascular dementia is a relatively common form of dementia.
      Anatomical changes of ageing in the brain arteries predispose the elderly to the
      effects of hypotension. Depending on their circulatory pattern, particular
      regions of the brain are susceptible to ischemic hypoperfusive lesions. These
      regions include the periventricular white matter, basal ganglia, and hippocampus.
      Interruption of prefrontal-basal ganglia circuits important for cognition and
      memory may result from these lesions. Hypotension and hypoperfusion explain the
      high risk for the development of cognitive impairment and vascular dementia in
      older patients affected by orthostatic hypotension, congestive heart failure, as
      well as in those undergoing surgical procedures such as hip and knee replacement
      and coronary artery bypass graft (CABG). Recognition of the susceptibility of
      elderly subjects to cerebral lesions induced by hypoperfusion should result in
      appropriate preventive measures and better treatment.

PMID- 15265264
TI  - Phenotypic profiles and functional genomics in Alzheimer's disease and in
      dementia with a vascular component.
AB  - Alzheimer's disease (AD) and dementia with vascular component (DVC) are the most
      prevalent forms of dementia. Both clinical entities share many similarities, but
      they differ in major phenotypic and genotypic profiles as revealed by structural
      and functional genomics studies. Comparative phenotypic studies have identified
      significant differences in 25% of more than 100 parametric variables, including
      anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy,
      blood pressure, blood biochemistry, hematology, thyroid function, folate and
      vitamin B12 levels, brain hemodynamics and lymphocyte markers. The phenotypic
      profile of patients with DVC differs from that of AD patients in the following:
      anthropometric values (weight, height); cardiovascular function (ECG, heart
      rate); blood pressure; lipid metabolism (HDL-CHO, TGs); uric acid metabolism;
      peripheral calcium homeostasis; liver function (GOT, GPT, GGT); alkaline
      phosphatase; lactate dehydrogenase; red and white blood cells; regional brain
      atrophy (left temporal region, inter-hippocampal distance); and left anterior
      blood flow velocity. Functional genomics studies incorporating APOE-related
      changes in biological markers extended the difference between AD and DVC up to
      57%. Brain perfusion studies show a severe brain hypoperfusion in dementia
      associated with enlarged age-dependent arterial perfusion times. Structural
      genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M,
      ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and
      DVC, with an absolute genetic variation rate ranging from 30% to 80%, depending
      upon genes and genetic clusters. Single gene analysis identifies relative genetic
      variations ranging from 0% to 5%. The relative polymorphic variation in genetic
      clusters integrated by two, three or four genes associated with AD ranges from 1%
      to 3%. The main phenotypic differences between AD and DVC are genotype-dependent,
      especially in AD, probably indicating that different genomic factors are
      determinant for the expression of dementia symptoms which might be accelerated or
      induced by environmental and/or cerebrovascular factors.

PMID- 15265265
TI  - 1H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) allows major metabolites to be
      measured noninvasively in defined regions of the living brain, and can detect
      biochemical abnormalities where conventional structural imaging appears normal.
      MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical
      abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other
      primary degenerative dementias have been investigated using MRS. Characteristic
      and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and
      elevated myo-inositol (mI) in the mesial temporal and parieto-occipital cortex.
      These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic
      distributions which reflect early pathological involvement and atrophy patterns
      in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline
      containing compounds (Cho) have also been reported. Similar changes are seen in
      VaD; mostly in white matter, whereas in AD they predominate in cortical grey
      matter. The regional distribution of grey matter involvement may differ between
      AD and other degenerative dementias. Hence, both the nature and anatomic
      distribution of metabolite abnormalities contribute to diagnostic discrimination
      with MRS. NAA/mI ratios from short echo time spectra of the posterior cingulate
      region cortex discriminate reliably between AD subjects, normal individuals and
      those with VaD, and provides a useful clinical test, as an adjunct to structural
      imaging. Elevated mI is detected in mild cognitive impairment (MCI) and
      quantitative metabolite measures correlate with degrees of cognitive impairment
      in AD; these suggest a possible role for MRS in early diagnosis and for surrogate
      biochemical markers for monitoring disease progression and therapeutic response.

PMID- 15265266
TI  - Relevance of functional neuroimaging in the progression of mild cognitive
      impairment.
AB  - AIM: To assess whether combining neuropsychological tests and cerebral blood flow
      markers improves progression accuracy from mild cognitive impairment (MCI) to
      Alzheimer's disease (AD) than each of them on its own. METHODS: Forty-two
      patients were investigated prospectively, undergoing baseline and 3-year follow
      up neuropsychological tests and neuroimaging with Tc-ECD-SPECT. Twenty-one
      patients had developed AD while 21 retained their initial diagnosis. The relative
      blood flow and cognitive differences were studied. Validity parameters,
      multivariant analysis and logistic regression model were calculated. RESULTS:
      Patients who deteriorated showed lower scoring than stable subjects in some
      neuropsychological tests (p = 0.03-0.001) and in relative blood flow in selected
      regions (8-10%). Low cognitive test scoring and low relative blood flow in some
      regions showed sensibilities and specificities from 70% to 86% for the diagnosis
      of early Alzheimer's disease. The relative risk of progression to AD was up to
      4.7 times higher for these patients (p = 0.0001). The left frontal relative blood
      flow, the CAMCOG and orientation scoring were the best data to predict the risk
      of progression to AD. CONCLUSIONS: The combination of functional imaging and
      neuropsychological tests can diagnose with high sensitivity and specificity if a
      patient is suffering cognitive impairment in its early stages, and may aid in
      predicting the risk of developing dementia.

PMID- 15265267
TI  - Gender differences in the relation of hypertension to cognitive function in older
      adults.
AB  - Here we examined potential interactive relations of hypertension and gender to
      cognitive function in 98 healthy, older adults (ages 55-83 years; 64% male; 92%
      White). After statistical adjustment for age and education, hypertensives
      performed significantly more poorly than normotensives on tests of motor speed
      and manual dexterity (p < 0.05). The adverse consequences of hypertension in
      older adults was more pronounced for female than male hypertensives on tests of
      delayed visual memory, visual attention and working memory, visuoconstructional
      ability, motor speed and manual dexterity for the non-dominant hand (p < 0.05);
      these are dimensions of performance for which female gender may be a relative
      disadvantage. The findings suggest the need to further examine subgroups that are
      vulnerable to the cognitive correlates of hypertension. The results also
      highlight the need for increased attention to blood pressure control in older
      adults for the preservation of cognitive function.

PMID- 15265268
TI  - Magnetic resonance angiography and vascular corrosion casting as tools in
      biomedical research: application to transgenic mice modeling Alzheimer's disease.
AB  - In vivo imaging technologies are presently receiving considerable attention in
      the biomedical and pharmaceutical research areas. One of the principal imaging
      modalities is magnetic resonance imaging (MRI). The multiparametric nature of MRI
      enables anatomical, functional and even molecular information to be obtained non
      invasively from intact organisms at high spatial resolution. Here we describe the
      use of one MRI modality, namely angiography (MRA), to non-invasively study the
      arterial vascular architecture of APP23 transgenic mice modeling Alzheimer's
      disease. Because the spatial resolution of the technique is limited, the in vivo
      studies are complemented by a powerful analysis of the vasculature using vascular
      corrosion casting. Both techniques revealed age-dependent blood flow alterations
      and cerebrovascular abnormalities in these mice. Our experience suggests that MRA
      complemented by cast analysis are important tools to describe vascular
      alterations and test new therapy concepts in animal models of AD. Furthermore,
      being non-invasive, MRA can also be applied to studies in patients suffering from
      this disease.

PMID- 15265269
TI  - Alzheimer's disease is a vasocognopathy: a new term to describe its nature.
AB  - Considerable evidence now indicates that Alzheimer's disease (AD) is a vascular
      disorder with neurodegenerative consequences. As a result, AD and vascular
      dementia (VaD) can each be described as a 'vasocognopathy'. The term better
      describes the origin of the disease (vaso: vessel/blood flow), its primary effect
      on a system (-cogno: relating to cognition) and its clinical course (-pathy:
      disorder). Evidence that AD is a vasocognopathy is partly supported by the
      following multidisciplinary findings: (1) epidemiologic studies linking AD and
      vascular risk factors to cerebral hypoperfusion; (2) evidence that AD and
      vascular dementia (VaD) share practically all reported risk factors; (3) evidence
      that pharmacotherapy which increases or improves cerebral perfusion lowers AD
      symptoms; (4) evidence of preclinical detection of AD candidates using regional
      cerebral perfusion and glucose uptake studies; (5) evidence of overlapping
      clinical symptoms in AD and VaD; (6) evidence of parallel cerebrovascular and
      neurodegenerative pathologic markers (including plaques and tangles) in AD and
      VaD; (7) evidence that cerebral infarction increases AD incidence by 50%; (8)
      evidence that chronic brain hypoperfusion can trigger hypometabolic, cognitive
      and neurodegenerative changes typical of AD; (9) evidence that most autopsied AD
      brains contain cerebrovascular pathology; (10) evidence that mild cognitive
      impairment (a transition stage for AD) converts to AD or VaD in 48% and 56% of
      cases, respectively, within several years. The collective evidence presented here
      poses a powerful argument for the re-classification of AD as a vascular disorder.
      Re-classification would allow a new strategy that could result in the tactical
      development and application of genuinely effective treatments, provide earlier
      diagnosis and reduce AD prevalence by focusing on the root of the problem.

PMID- 15265270
TI  - Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis
      of sporadic Alzheimer's disease.
AB  - We postulate that severe atherosclerotic occlusion of the circle of Willis and
      leptomeningeal arteries is an important factor in the pathogenesis of some
      sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated
      by an overwhelming amyloid accumulation in the walls of leptomeningeal and
      cortical arteries resulting in a significant decrease in perfusion pressure and
      consequent ischemia/hypoxia of the brain tissue. We also propose that the distal
      areas of the white matter (WM) will be the first affected by a lack of oxygen and
      nutrients. Our hypotheses are supported by the following observations: (1) the
      number of stenoses is more frequent in AD than in the control population (p =
      0.008); (2) the average index of occlusion is greater in AD than in the control
      group (p < 0.00001); (3) the index of stenosis and the total number of stenoses
      per case are positively correlated (R = 0.67); (4) the index of stenosis
      correlates with the neuropathological lesions of AD and with the MMSE
      psychometric test; (5) the number and degree of atherosclerosis of the anterior,
      middle and posterior cerebral arteries is more severe in cases of AD than in the
      control population; (6) atherosclerosis severity is apparently associated with
      the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with
      the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell
      count and microvessel count in the areas of WM rarefaction correlate with the
      neuropathological lesions of AD and with the MMSE score. Our data strongly
      suggest that severe hemodynamic disturbances contribute to sporadic AD and
      support the numerous observations indicating cardiovascular system participation
      in the pathogenesis of these dementias.

PMID- 15265271
TI  - Vascular inflammatory, oxidative and protease-based processes: implications for
      neuronal cell death in Alzheimer's disease.
AB  - A substantial literature demonstrates activation of inflammatory processes in the
      Alzheimer's disease (AD) brain and an association between inflammation and
      oxidative stress. We have shown that brain microvessels from AD patients express
      high levels of inflammatory proteins and that these proteins evoke release of the
      neurotoxic protease thrombin from brain endothelial cells. The objective of this
      study was to determine the effects of inflammatory proteins on brain endothelial
      cell reactive oxygen species generation, protease release and cell apoptosis.
      Also, the effects of inflammatory proteins on neuronal reactive oxygen species
      generation, injury and apoptosis were assessed. Treatment of cultured brain
      endothelial cells with inflammatory proteins (LPS, IL-1beta, IL-6, IFN-gamma, TNF
      alpha) resulted in a significant increase (p < 0.01) in intracellular levels of
      reactive oxygen species by 1 h. Inflammatory proteins also caused release of
      tissue plasminogen activator and increased apoptosis by 24 h in these cells. In
      cultured neurons, inflammatory proteins caused an increase in reactive oxygen
      species, membrane fluidity, and apoptosis by 24 h, as detected by fluorescent
      microscopy. Taken together, these data support the hypothesis that vascular
      inflammatory, oxidative and protease-based processes contribute to neuronal cell
      death, and suggest that therapies targeted at these mediators and processes could
      be effective in AD.

PMID- 15265272
TI  - Is nitric oxide a key target in the pathogenesis of brain lesions during the
      development of Alzheimer's disease?
AB  - Nitric oxide (NO) is a short-life key bioregulatory active molecule in the
      cardiovascular, immune and nervous systems. NO is synthesized by converting L
      arginine to L-citrulline by enzymes called NO synthase (NOS). The growing body of
      evidence strongly supports the theory that this molecule appears to be one of the
      key targets for the disruption of normal brain homeostasis, which causes the
      development of brain lesions and pathology such as in Alzheimer's disease (AD) or
      other related dementia. The vascular content of NO activity appears especially to
      be a main contributor to this pathology before the over-expression of other NOS
      isoforms activity in a different brain cellular compartment. We speculate that
      pharmacological intervention using NO donors and/or NO suppressors will be able
      to delay or minimize the development of brain pathology and further progression
      of mental retardation.

PMID- 15265273
TI  - Increased homocysteine and decreased adenosine formation in Alzheimer's disease.
AB  - Vascular risk factors increase the risk of Alzheimer's disease. Increased
      concentrations of circulating homocysteine are associated with vascular risk
      factors and Alzheimer's disease but the underlying mechanisms are unclear.
      Homocysteine inhibits the hydrolysis of S-adenosylhomocysteine leading to a
      decrease in the intracellular adenosine concentration. Adenosine is an endogenous
      protective molecule against atherosclerotic and vaso-occlusive disorders that
      contribute to the pathology of Alzheimer's disease. In this study the
      concentrations of homocysteine and adenosine were determined in the plasma of 25
      patients with Alzheimer's disease and 25 control subjects. There was a
      significant increase in the plasma concentration of homocysteine (p < 0.0001) and
      a significant decrease in the plasma concentration of adenosine (p < 0.001). In
      the combined Alzheimer and control groups a significant negative correlation was
      found between the plasma concentrations of homocysteine and adenosine (r = 
      0.769, p < 0.0001). There was also a significant negative correlation between the
      plasma concentrations of homocysteine and adenosine in the Alzheimer group (r =
      0.773, p < 0.0001). The decrease in adenosine formation may play a role in the
      vascular pathology of homocysteine in Alzheimer's disease.

PMID- 15265274
TI  - CADASIL: what component of the vessel wall is really a target for Notch 3 gene
      mutations?
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to
      cognitive decline, dementia and recurrent strokes. The underlying angiopathy of
      the small vessels is characterized by basophilic degeneration of the media, Notch
      3 protein accumulation in vessel wall and a unique type of ultrastructural
      deposits located nearby the basal lamina. In some cases of CADASIL, morphological
      changes similar to those observed in panarteritis nodosa (PAN) were found. PAN
      like changes manifested as fibrinoid necrosis of the tunica media and
      perivascular inflammatory infiltrates were found in arteries not only in the
      central nervous system but also in internal organs. Presence of PAN-like changes
      indicates that some autoimmunological mechanisms can participate in the CADASIL
      process. Although vascular smooth muscle cells seem to be a primary target of the
      pathogenic process triggered by mutations in Notch 3 gene they are probably not
      the only target. This article gives a brief overview on the morphologic spectrum
      of the vascular pathological changes in CADASIL and discusses some of the
      relevant mechanisms that lead from Notch 3 mutations to ischemic infarcts.

PMID- 15265275
TI  - Nitric oxide pathways in Alzheimer's disease and other neurodegenerative
      dementias.
AB  - Nitric oxide (NO) is an enzymatic product of nitric oxide synthase (NOS). NO has
      significant physiological functions and an increasing body of evidence suggests
      that NO pathways are implicated in a number of neurological disorders, including
      Alzheimer's disease (AD) and other neurodegenerative dementias. NO is
      continuously released by endothelial cells in the vascular system, whereas
      advanced age in the presence of vascular risk factor causes a decrease in
      cerebral blood flow, involving microvasculopathy with impaired NO release, which
      in turn results in regional metabolic dysfunction. This finding suggests that
      vascular pathology plays a crucial role in the pathogenesis of so-called
      neurodegenerative dementias. Inflammatory responses are commonly found in the
      brain under a variety of neurodegenerative dementias, including AD and dementia
      with Lewy bodies, in which up-regulation of NOS expression, suggesting
      overproduction of NO, is found in neurons and glia. NO is thought to be involved
      in such neuroinflammation due to its free radical properties, which compromise
      cellular integrity and viability via mitochondrial damage. Further studies to
      elucidate NO pathways in neurodegenerative dementias could lead to a better
      understanding of their pathogenesis and improved therapeutic strategies, and
      therefore are certainly warranted.

PMID- 15265276
TI  - The relationships between atherosclerosis, heart disease, type 2 diabetes and
      dementia.
AB  - Type 2 diabetes in the elderly is associated with increased incidence of vascular
      disease, particularly, atherosclerosis of large blood vessels. Together with
      other risk factors such as dyslipidemia, atherosclerosis increases the risk for
      coronary heart disease and stroke. Most studies that have examined the impact of
      type 2 diabetes and other heart disease risk factors on cognitive functions do
      not provide evidence that heart disease risk factors (with the possible exception
      of triglycerides) further increase the likelihood of observing cognitive deficits
      in diabetic patients. However, none of these studies used imaging techniques to
      evaluate atherosclerosis or evidence of cerebrovascular disease, such as
      infarctions. The few studies that have included brain imaging suggest that
      evidence of cerebrovascular disease further increases the risk for dementia in
      diabetic patients. The results of longitudinal studies suggest that diabetes is
      an independent risk factor for cognitive decline and dementia. The pattern of
      neuropsychological performance observed in type 2 diabetic patients appears to be
      the result of multiple interacting processes developing over time. In addition to
      the detrimental effects of protracted impaired glucose regulation on the central
      nervous system, type 2 diabetes pathology also encompasses the detrimental
      effects of associated complications such as cerebrovascular disease, which is
      likely the main cause of the observed processing speed/reaction time decrements.

PMID- 15265277
TI  - The nature and effects of cortical microvascular pathology in aging and
      Alzheimer's disease.
AB  - Age-related and amyloid-induced pathology of the cerebral microvasculature have
      been implicated as potential contributing factors to the pathogenesis of
      Alzheimer's disease (AD). The microvasculature plays a crucial role in
      maintaining brain homeostasis and deterioration of its integrity may have
      deleterious effects on brain function in AD, possibly leading to neurofibrillary
      degeneration, plaque formation, and cell loss. Brain vessels possess peculiar
      anatomical and physiological properties owing to their role in the exchange
      processes of various substances between blood and brain, which are highly
      regulated for the maintenance of ionic homeostasis of the neuronal environment.
      Here we review neuropathological aspects of cortical microvessels in aging and AD
      in relationship to known cardiovascular risk factors and their possible impact on
      the cognitive decline seen in late-onset dementia.

PMID- 15265278
TI  - Influence of beta-amyloid fibrils on the interactions between red blood cells and
      endothelial cells.
AB  - Alzheimer's disease is associated with vascular amyloidosis. As blood flows
      through the microcirculation, red blood cells (RBCs) come in contact with the
      vasculature. RBCs as well as endothelial cells (ECs) are known to bind beta
      amyloid fibrils. This suggests that a potential effect of amyloidosis may involve
      the interactions of RBCs with ECs lining the wall of the blood vessels mediated
      by amyloid fibrils. We have studied the effect of beta-amyloid peptide[1-40]
      (Abeta1-40) fibrils on the interactions of murine RBCs with ECs derived from
      bovine lung microvascular endothelium (BLMVEC) as well as bovine pulmonary
      arterial endothelium (BPAEC) in culture. We show that the initial incorporation
      of Abeta fibrils onto either RBCs or ECs cause RBCs to adhere to the ECs with
      greater affinity for the microvascular cells than the arterial cells. In
      addition, there is a transfer of Abeta fibrils between the RBCs and the ECs. Both
      the transfer and adhesion occurs when the amyloid fibrils are on the ECs or on
      the RBCs. However, with the amyloid fibrils on the RBCs, the adhesion and the
      transfer are greater than with the fibrils on the ECs. These results suggest that
      amyloidosis may affect the flow of RBCs through the microcirculation and that
      RBCs may play a role in propagating amyloidosis through the vasculature.

PMID- 15265279
TI  - The evolution of omentum transposition: from lymphedema to spinal cord, stroke
      and Alzheimer's disease.
AB  - It is now well established that the omentum incorporates into its tissues a
      variety of biological factors that exert a favorable effect on the central
      nervous system. Physiological characteristics of the omentum include edema
      absorption, fibrotic inhibition, blood-brain barrier penetration and, of major
      importance, angiogenic activity. Over several decades, studies have shown
      increasing clinical uses of the omentum following its placement on various
      structures within the body. This paper details the evolution of omental
      transposition (OT) up to the present at which time OT is being applied to the
      brain of Alzheimer disease (AD) patients. Success in this area raises the
      possibility that the omentum may prove to be a present-day treatment for patients
      with AD until future pharmaceutical and/or genetic forms of treatment are
      developed.

PMID- 15265280
TI  - Is mild vascular cognitive impairment reversible? Evidence from a study on the
      effect of carotid endarterectomy.
AB  - Mild vascular cognitive impairment (mVCI) is a broader term that is intended to
      detect cognitive loss before the development of dementia. The identification of
      preventable risk factors as well as therapeutic strategies of intervention is
      still unclear. It has been suggested that carotid endarterectomy (CEA) improves
      cognitive functions, beyond the well-known preventive effect upon future stroke
      events. In the present study, we evaluated the beneficial effect of CEA in
      restoring mVCI. Among a large sample of subjects, who underwent CEA for severe
      carotid stenosis, two groups were identified according to the absence (CON) or
      the presence of cognitive impairment (mVCI). A multidimensional
      neuropsychological and behavioural assessment was performed in the week prior,
      and at a 3-month follow-up after CEA. The incidence of mVCI in this sample was
      38%. Seventy-eight patients completed the follow-up (48 CON, 30 mVCI). Both
      groups showed a clinical improvement after CEA, although the effect was
      significantly higher in the mVCI group in regard to verbal memory (short story, p
      < 0.05), and attention (digit span, p < 0.05) scores. At follow-up, 60% of mVCI
      subjects were classified as having normal cognitive functions. Index of disease
      severity and peripheral arterial disease were found to be the predictors of
      improvement. These findings support that mVCI represents a heterogeneous, in some
      cases reversible condition. CEA might be considered a therapeutic option to treat
      and prevent cognitive decline in mVCI patients.

PMID- 15265281
TI  - Antioxidants for the treatment of mild cognitive impairment.
AB  - The isolated deficit in recent memory frequently associated with decline to
      Alzheimer's disease (AD) is defined as mild cognitive impairment (MCI). The
      observed progression of MCI to AD suggests a common pathogenesis between these
      two clinical syndromes, and several neuroimaging, neuropsychological and
      biological methods are applied with the purpose of identifying subjects at risk
      of AD. Among these methods, the evaluation of a condition of oxidative stress is
      gaining increasing attention. Since oxidative stress seems to be involved in the
      earliest phases of AD, and MCI may be considered as a prodromal phase of
      dementia, it is an attractive issue to focus therapeutic interventions on the
      early phase of the disease.

PMID- 15265282
TI  - Treatment of vascular dementia-evidence from clinical trials with cholinesterase
      inhibitors.
AB  - Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from
      cardiovascular disease, are common causes of dementia and cognitive decline in
      the elderly. Also, CVD frequently contributes to cognitive loss in patients with
      Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism
      involved in vascular cognitive impairment and vascular dementia (VaD) has
      resulted in promising treatments of these conditions. Cholinergic deficits in VaD
      are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can
      be treated with the use of the cholinesterase inhibitors used in AD. Controlled
      clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as
      in patients with AD plus CVD, have demonstrated improvement in cognition,
      behavior and activities of daily living.

PMID- 15265283
TI  - Cultured mucosal cell sheet with a double layer of keratinocytes and fibroblasts
      on a collagen membrane.
AB  - The aim of this study was to develop a novel cultured mucosal membrane that was
      facile to prepare and easy to handle, and that could be applied to mucosal
      defects in the oral cavity. Human oral keratinocytes and fibroblasts were
      prepared from the oral mucosa. We made the following two types of cultured
      mucosal cell sheets: a monolayer sheet of keratinocytes cultured on a collagen
      membrane (K-S) and a double-layered sheet of keratinocytes and fibroblasts on a
      collagen membrane (KF-S). A collagen membrane was used as a control. Each type of
      sheet was transplanted onto dorsal skin defects of nude mice. The wound area was
      measured for the assessment of wound contraction and a specimen was harvested for
      histologic evaluation 1 week and 4 weeks after grafting. Wound contraction was
      minimal with KF-S grafts. Although histologic examination showed normal
      differentiation of the epithelium in all graft types, the involucrin expression
      pattern of KFS was most similar to that of normal epithelium. These results
      indicate that a double-layered sheet of keratinocytes and fibroblasts cultured on
      a collagen membrane may facilitate epithelial healing and prevent wound
      contraction.

PMID- 15265284
TI  - Regeneration of hyaline articular cartilage with irradiated transforming growth
      factor beta1-producing fibroblasts.
AB  - The regeneration of hyaline articular cartilage by cell-mediated gene therapy
      using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH
      3T3-TGF-beta(1)) has been reported previously. In this study, we investigated
      whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of
      radiation are still capable of inducing the regeneration of hyaline articular
      cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80
      Gy, using a irradiator, and then injected into artificially made partial defects
      on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6
      weeks postinjection and hyaline articular cartilage regeneration was evaluated by
      histological and immunohistochemical staining (n = 5 per each group). Irradiated
      NIH 3T3-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation;
      moreover, the kinetics of their viability were similar regardless of the
      radiation intensity. TGF-beta1 expression, measured by ELISA, showed that the TGF
      beta(1) protein produced from the irradiated cells peaked 5 days after
      irradiation and thereafter declined rapidly. Complete filling of the defect with
      reparative tissue occurred in all the groups, although variations were observed
      in terms of the nature of the repair tissue. Histological and immunohistochemical
      staining of the repair tissue showed that the tissue newly formed by irradiated
      NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage
      like characteristics, as was observed in the nonirradiated controls. On the other
      hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with
      40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that
      TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose
      (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo.
      Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be
      clinically useful and an efficient method of regenerating hyaline articular
      cartilage.

PMID- 15265285
TI  - Tissue engineering of an auricular cartilage model utilizing cultured chondrocyte
      poly(L-lactide-epsilon-caprolactone) scaffolds.
AB  - To determine the potential development in vivo of tissue-engineered auricular
      cartilage, chondrocytes from articular cartilage of bovine forelimb joints were
      seeded on poly(L-lactic acid-epsilon-caprolactone) copolymer scaffolds molded
      into the shape of a human ear. Copolymer scaffolds alone in the same shape were
      studied for comparison. Chondrocyte-seeded copolymer constructs and scaffolds
      alone were each implanted in dorsal skin flaps of athymic mice for up to 40
      weeks. Retrieved specimens were examined by histological and molecular
      techniques. After 10 weeks of implantation, cell-seeded constructs developed
      cartilage as assessed by toluidine blue and safranin-O red staining; a vascular,
      perichondrium-like capsule enveloped these constructs; and tissue formation
      resembled the auricular shape molded originally. Cartilage matrix formation
      increased, the capsule persisted, and initial auricular configuration was
      maintained through implantation for 40 weeks. The presence of cartilage
      production was correlated with RT-PCR analysis, which showed expression of bovine
      specific type II collagen and aggrecan mRNA in cell-seeded specimens at 20 and 40
      weeks. Copolymer scaffolds monitored only for 40 weeks failed to develop
      cartilage or a defined capsule and expressed no mRNA. Extensive vascularization
      led to scaffold erosion, decrease in original size, and loss of contour and
      shape. These results demonstrate that poly(L-lactic acid-epsilon-caprolactone)
      copolymer seeded with articular chondrocytes supports development and maintenance
      of cartilage in a human ear shape over periods to 40 weeks in this implantation
      model.

PMID- 15265286
TI  - Bone regeneration by grafting of cultured human bone.
AB  - A 3-mL sample of bone marrow was collected from the iliac bones of 27 orthopedic
      patients (8 men and 19 women with a mean age of 56.1 years [range, 17 to 76
      years]), followed by culture in standard culture medium (minimal essential medium
      containing 15% fetal bovine serum). In all 7 patients randomly selected from
      these 27 patients, significant in vitro osteogenic ability of marrow mesenchymal
      cells was demonstrated by scanning electron microscopy and biochemical analyses.
      In all 27 cases, to investigate the in vivo osteogenic potential of this human
      cultured bone, porous ceramics were impregnated with marrow cells and subcultured
      in osteogenic culture medium (standard medium supplemented with sodium beta
      glycerophosphate, vitamin C phosphate, and dexamethasone). After 3 weeks of
      subculture, the cultured artificial bones of the cultured bone/porous ceramics
      were grafted into the abdominal cavity of nude mice. Histological and biochemical
      (alkaline phosphatase activity and human osteocalcin) examinations indicated that
      the cultured artificial bone possessed significant ability to regenerate bone.
      This result suggests that the bone-regenerating ability of human marrow cells may
      not depend on age, and that cultured artificial bone may be useful for bone
      regeneration treatment if appropriate cultured marrow cells can be successfully
      prepared.

PMID- 15265287
TI  - Vascular smooth muscle cells on hyaluronic acid: culture and mechanical
      characterization of an engineered vascular construct.
AB  - Esterified hyaluronic acid (HYAFF) is routinely used for clinical tissue
      engineering applications such as skin and cartilage. The material is degraded by
      neotissue formation and degradation products are highly biocompatible. In the
      present article we investigate the possibility to culture vascular smooth muscle
      cells on this biodegradable material for the generation of tubular constructs to
      be used for vascular tissue engineering. We have evaluated cell attachment and
      growth, and the possibility to obtain a three-dimensional tubular shape culture
      from flat HYAFF sheets. We also evaluated the mechanical properties of the cell
      constructs, using a specific testing protocol, and compared them with the
      properties of segments of porcine coronary artery. Morphology and viability tests
      demonstrated that vascular cells, either from porcine or human origin, adhere and
      grow on nonwoven meshes of HYAFF, and that precoating of the material with
      fibronectin or collagen had a modest effect on cell growth and extracellular
      matrix production. Cell growth reached a maximum 7 days after seeding. Simple
      wrapping of flat sheets of nonwoven meshes containing vascular cells around a
      cylindrical mandrel, and culture under static conditions for 14 days, yielded
      tubular constructs suitable for mechanical tests. Despite cell colonization,
      constructs showed lower mechanical resistance as compared with porcine coronary
      arteries. The material used and the technique developed result in highly
      cellularized tubular constructs. Whether the mechanical properties may be
      improved by dynamic culture conditions is worthy of investigation.

PMID- 15265288
TI  - Transcellular water transport and stability of expression in aquaporin 1
      transfected LLC-PK1 cells in the development of a portable bioartificial renal
      tubule device.
AB  - We investigated a portable bioartificial renal tubule device (BRTD) consisting of
      renal tubule cells and hollow fibers, to improve the quality of life of patients.
      It is necessary for a BRTD system to be compact. A compact portable BRTB requires
      transfection of an appropriate water channel or electrical pump genes in tubular
      epithelial cells, which should be based on physiological similarities to human
      kidney function. LLC-PK(1) cells, into which rat kidney aquaporin 1 (AQP1) cDNA
      was stably transfected, were evaluated for water transport ability. The
      expression and localization of water AQP1 were examined by Western blotting, RT
      PCR, and immunofluorescence. To measure transcellular water permeation, a simple
      method was applied, using phenol red as a cell-impermeant marker of
      concentration. In contrast to wild-type LLC-PK(1) cells, rat AQP1-transfected
      cells had high transcellular osmotic water permeability. The expression of rat
      AQP1 mRNA (ratio of AQP1 to beta-actin mRNA) and protein bands (a 28-kDa band and
      a broad, 35- to 45-kDa band) was confirmed to be stably maintained until a
      population doubling level of 24. In AQP1-transfected LLCPK(1) cells, the protein
      was localized mainly to the basolateral side, but also the apical side, of the
      plasma membrane. Wild-type LLC-PK(1) cells were not stained at the plasma
      membrane. It is possible that enough AQP1-transfected tubule epithelial cells
      were supplied for a bioartificial renal tubule device.

PMID- 15265289
TI  - Fetal liver as a source of autologous progenitor cells for perinatal tissue
      engineering.
AB  - Mesenchymal progenitor cells, isolated from adult bone marrow, have been shown to
      have utility for autologous tissue engineering. The possibility of isolating from
      the fetal hematopoietic system a cell population with similar potential, which
      could be used for autologous reconstruction of prenatally diagnosed congenital
      anomalies, has not been explored to date. Liver stromal cells isolated from a
      portion of the right lateral hepatic lobe of midgestation fetal lambs were
      expanded in vitro. Passage 1 cells displayed a uniform fibroblast-like morphology
      but could be induced to differentiate into skeletal muscle, adipocytes,
      chondrocytes, and endothelial cells by selective medium supplementation. By
      manipulating the extracellular matrix in vitro, spontaneously contracting cardiac
      myocyte-like cells could be generated as well. Multilineage differentiation was
      confirmed by morphology, protein expression, and upregulation of lineage-specific
      mRNA. The potential for engineering myocardial tissue was then investigated by
      transplanting early-passage progenitor cells, organized on a three-dimensional
      matrix, into the ventricle of an immunocompromised rat utilizing a previously
      described model of left ventricular tissue engineering. Survival, incorporation
      into the host myocardium, and cardiomyocytic differentiation of the transplanted
      cells were confirmed. We have demonstrated that mesenchymal progenitor cells with
      multilineage potential can be isolated from the fetal liver and have potential
      utility for autologous tissue engineering.

PMID- 15265290
TI  - Maturation and integration of tissue-engineered cartilages within an in vitro
      defect repair model.
AB  - This study compared the behavior of four different engineered cartilages in a
      hybrid culture system. First, the growth and maturation of tissue-engineered
      cartilages in isolation were compared to those grown in an in vitro articular
      cartilage defect repair model. Tissue-engineered cartilages using fibrin,
      agarose, or poly(glycolic acid) scaffolds were implanted into annular explants of
      articular cartilage and cultured for 20 or 40 days. Native tissue had a
      substantial influence on the DNA, sulfated glycosaminoglycan, and hydroxyproline
      content of the engineered tissues, suggesting that the presence of living tissue
      in the culture significantly altered cell proliferation and matrix accumulation.
      Second, the adhesion strength of various engineered cartilages to native tissue
      was measured and compared with the biochemical content of the engineered tissues.
      All scaffold treatments adhered to the native cartilage, but there were
      statistically significant differences in adhesive strength between the different
      scaffolds. The adhesive strength of all engineered scaffolds was significantly
      lower than that of native tissue to itself. In the engineered tissues, neither
      failure stress nor energy to failure correlated with gross biochemical content,
      suggesting that adhesion between native and engineered tissues is not purely a
      function of gross matrix synthesis.

PMID- 15265291
TI  - Demineralized bone matrix-induced ectopic bone formation in rats: in vivo study
      with follow-up by magnetic resonance imaging, magnetic resonance angiography, and
      dual-energy X-ray absorptiometry.
AB  - The aim of this study was to further explore the use of magnetic resonance
      imaging (MRI), magnetic resonance angiography (MRA), and dual-energy X-ray
      absorptiometry (DEXA) to assess bone formation and blood circulation in a
      pedicled bone graft substitute. In 14 Wistar rats, initially 10 weeks old,
      heterogeneous demineralized femur bone matrix implants were wrapped in pedicled
      adductor thigh muscle flaps. One rat died after surgery. Subsequently, bone
      formation and maintenance of blood vessel functionality were evaluated in six
      rats 6 weeks postimplantation by means of in vivo MRI/MRA and postmortem
      histomorphometry. The other seven rats were left for 12 weeks, whereafter bone
      formation was evaluated by in vivo DEXA and postmortem histomorphometry. The
      results demonstrated that after 6 weeks bone formation was present in four of six
      animals, quantified as 42 (+/-35)% and 25 (+/-19)% by means of MRI and
      histomorphometry, respectively. MRA was able to show patency of the pedicles of
      these four rats only, which suggests that the lack of blood supply in the other
      two rats is the cause of the failure to form bone. In the 12-week group,
      histology showed increased bone formation without signs of osteolysis, which was
      quantified histomorphometrically to be as high as 48 (+/-15)%. DEXA failed to
      show bone formation. It is concluded that in vivo MRI proved to be a reliable
      method for monitoring ectopic bone formation in a rat model, whereas in vivo DEXA
      was unable to detect the implants. Furthermore, in vivo MRA proved to be a useful
      technique for studying the circulation of muscle flaps in this animal model.

PMID- 15265292
TI  - Engineering of functional tendon.
AB  - Surgical tendon repair is limited by the availability of viable tissue for
      transplantation. Because of its relatively avascular nature, tendon is a prime
      candidate for engineered tissue replacement. To address this problem, cells
      isolated from rat Achilles tendon were grown to confluence in culture and allowed
      to self-assemble into a cylinder between two anchor points. The resulting
      scaffold-free tissue was composed of aligned, small-diameter collagen fibrils, a
      large number of cells, and an excess of noncollagenous extracellular matrix; all
      characteristics of embryonic tendon. The stress-strain response of the constructs
      also resembles the nonlinear behavior of immature tendons, and the ultimate
      tensile strength is approximately equal to that of embryonic chick tendon,
      roughly 2 MPa. These physical and mechanical properties indicate that these
      constructs are the first viable tendons engineered in vitro, without the aid of
      artificial scaffolding.

PMID- 15265293
TI  - Cell yield, proliferation, and postexpansion differentiation capacity of human
      ear, nasal, and rib chondrocytes.
AB  - Human ear, nasal, and rib chondrocytes were compared with respect to their
      suitability to generate autologous cartilage grafts for nonarticular
      reconstructive surgery. Cells were expanded for two passages in medium containing
      10% fetal bovine serum without (control) or with transforming growth factor
      beta(1) (TGF-beta(1)), fibroblast growth factor 2 (FGF-2), and platelet-derived
      growth factor bb (PDGF-bb) (TFP). Expanded cells were cultured as three
      dimensional pellets in chondrogenic serum-free medium containing insulin,
      dexamethasone, and TGF-beta(1). Chondrocytes from all three sources were
      successfully isolated, increased their proliferation rate in response to TFP, and
      dedifferentiated during passaging. Redifferentiation by ear and nasal, but not
      rib, chondrocytes was enhanced after TFP expansion, as assessed by the
      significant increase in glycosaminoglycan (GAG)/DNA content and collagen type II
      mRNA expression in the resulting pellets. TFP-expanded ear and nasal chondrocytes
      generated pellets of better quality than rib chondrocytes, as assessed by the
      significantly higher GAG/DNA content and collagen type II mRNA expression, and by
      the relative stain intensities for GAG and collagen types I and II. In
      conclusion, postexpansion cell yields suggest that all three sources investigated
      could be used to generate autologous grafts of clinically relevant size. However,
      ear and nasal chondrocytes, if expanded with TFP, display superior postexpansion
      chondrogenic potential and may be a preferred cell source for cartilage tissue
      engineering.

PMID- 15265294
TI  - Transplantation of endothelial progenitor cells into the lung to alleviate
      pulmonary hypertension in dogs.
AB  - Primary pulmonary hypertension (PPH) is still a refractory disease, and patients
      deteriorate despite any treatment. We hypothesized that neovascularization in the
      lung could increase the volume of the vascular bed in the pulmonary circulation
      and thus reduce the development of pulmonary hypertension (PH). Endothelial
      progenitor cells (EPCs) might be a potential cell source for neovascularization.
      We examined the effects of EPC transplantation into the lungs of dogs with
      dehydromonocrotaline-induced PH. The lung parenchyma of PH model dogs was
      injected with ex vivo-expanded, autologous EPCs originated from peripheral blood
      (experiments, n=4) or culture medium (control, n=3), using a bronchoscope. EPC
      transplantation gave significant improvements in mean pulmonary artery pressure,
      cardiac output, and pulmonary vascular resistance. Histological evaluation
      revealed both improvement in the medial thickness of the small pulmonary artery
      and neovascularization of the lung tissue. These results indicate that EPC
      transplantation into the lung is effective at preventing the progression of
      dehydromonocrotaline-induced PH in dogs, and suggest a new therapeutic option for
      PPH.

PMID- 15265295
TI  - Hydrodynamic shear stimulates osteocalcin expression but not proliferation of
      bone marrow stromal cells.
AB  - Bone marrow stromal cells (BMSCs) are a promising component for engineered bone
      tissues, but in vitro formation of a bonelike tissue requires culture conditions
      that direct these multipotent cells toward osteoblastic maturation. Fluid flow
      has been postulated to stimulate bone tissue development in vivo, but the effect
      of shear stress on proliferation and differentiation of osteoprogenitor cell
      cultures in vitro has not been examined closely. In this study BMSCs were
      cultured on fibronectin-coated substrates and exposed intermittently (for 30 min
      3, 5, 7, 9, 11, and 13 days after seeding) to a spatially dependent range of
      shear stresses (0.36 to 2.7 dyn/cm(2)) using a radial-flow chamber. After 7 days
      cell density did not vary between sheared and control cell layers. In contrast,
      after 21 days the accumulation of osteocalcin protein (OC) in cell layers was
      increased significantly relative to static controls, while the quantity of
      multilayer cell aggregates (i.e., bone nodules) was diminished. Neither of these
      effects varied systematically with shear magnitude. Finally, pretreatment of
      cultures with the cyclooxygenase (COX)-2-specific inhibitor NS-398 blocked
      prostaglandin secretion in response to shearing flow and significantly reduced OC
      accumulation in cell layers. These results provide evidence that flow stimulates
      osteoblastic maturation but not proliferation of bone marrow stromal cells and
      that prostaglandin signaling is involved in this effect.

PMID- 15265296
TI  - Capillary vessel network integration by inserting a vascular pedicle enhances
      bone formation in tissue-engineered bone using interconnected porous
      hydroxyapatite ceramics.
AB  - The aim of the present study was to investigate the possibility of integrating
      porous hydroxyapatite (HA) ceramics with a capillary vessel network via insertion
      of a vascular pedicle, and to determine whether this procedure enhances new bone
      formation in tissue engineering of bone. First, synthetic interconnected porous
      HA (IP-CHA) was implanted subcutaneously into rat groin with or without insertion
      of superficial inferior epigastric vessels. At 6 weeks, IP-CHA with vascular
      insertion contained thick fibrous connective tissue with a number of large blood
      vessels that seemed to derive from the inserted vascular bundle. Next, IP-CHA
      loaded with recombinant human bone morphogenetic protein 2 (BMP, 2 or 10
      microg/block) was implanted with or without vascular insertion. At 3 weeks, IP
      CHA/BMP (10 microg) composite with vascular insertion exhibited abundant new bone
      formation in the pores of the deep portion close to the inserted vessels. In
      contrast, IP-CHA/BMP (10 microg) without vascular insertion showed poor bone
      formation. Histomorphometric analysis demonstrated that vascular insertion
      significantly increased new bone formation. In IP-CHAs with a lower dose of BMP
      (2 microg), no bone formation was found, with or without vascular insertion.
      These results suggest that the present system of integrating a vascular network
      with IP-CHA is a useful technique for bone tissue engineering.

PMID- 15265298
TI  - Megakaryocyte-bone marrow stromal cell aggregates demonstrate increased colony
      formation and alkaline phosphatase expression in vitro.
AB  - Bone marrow stromal cells (BMSCs) possess certain stem celllike properties and
      can differentiate to adopt a number of mesenchymal phenotypes. BMSCs are usually
      investigated in vitro as homogeneous single-cell suspensions; however, these
      preparations lose much of their osteogenic capacity. Using the fibroblastic
      colony-forming unit assay, we have compared the proliferation and capacity to
      express alkaline phosphatase of BMSC-containing aggregates of bone marrow cells
      with single-cell suspensions of bone marrow cells from the same source.
      Aggregates were separated from single cells by density gradient centrifugation or
      cell sieving. The aggregate and single-cell preparations gave rise to similar
      numbers of colonies; however, the colonies produced by the aggregates were larger
      and expressed higher levels of alkaline phosphatase. When the aggregates were
      dissociated, colonies still formed; however, they expressed negligible levels of
      alkaline phosphatase. Immunomagnetic selection and immunofluorescent staining for
      CD61, N-methyl-D-aspartate (NMDA) receptor subunit 1, and acetylcholinesterase
      showed that the majority of the aggregates giving rise to osteoblastic colonies
      contained megakaryocytes. These data demonstrate that removing BMSCs from their
      normal environment reduces their osteoblastic capacity and that to achieve their
      maximal differentiation, BMSCs require direct physical contact with accessory
      cells such as megakaryocytes. These findings may be of direct relevance to the
      use of BMSCs for tissue-engineering purposes.

PMID- 15265297
TI  - Osteogenic differentiation of mouse embryonic stem cells: differential gene
      expression analysis by cDNA microarray and purification of osteoblasts by
      cadherin-11 magnetically activated cell sorting.
AB  - We have previously shown osteogenic differentiation of mouse embryonic stem (ES)
      cells and temporal enrichment with osteoblastic cells, by stimulation with serum
      containing culture medium supplemented with beta-glycerophosphate, ascorbate, and
      dexamethasone. In our present study we have used similar culture conditions to
      further investigate osteogenic differentiation of mouse ES cells. Using reverse
      transcription-polymerase chain reaction (RT-PCR) we demonstrated the expression
      of genes associated with osteoblast differentiation including the bone matrix
      protein osteocalcin and the transcription factor Cbfa-1/runx2. Furthermore,
      results of cDNA microarray analysis, and subsequent RT-PCR analysis of
      differentiating ES cells after exposure to osteogenic stimuli, revealed a
      combination of upregulation of genes involved in osteoblast differentiation
      including osteopontin, HSP-47, and IGF-II coupled with downregulation of genes
      involved in differentiation of other phenotypes such as the neuroectoderm factor
      Stra-13. Finally, we have applied magnetically activated cell-sorting methods to
      ES cell cultures treated with osteogenic stimuli and, using an antibody to
      cadherin-11, have purified a subpopulation of cells with osteoblastic
      characteristics.

PMID- 15265299
TI  - Novel collagen sponge reinforced with polyglycolic acid fiber produces robust,
      normal hair in murine hair reconstitution model.
AB  - The hair reconstitution assay is a useful system for studying cell-cell and
      epithelial-mesenchymal interaction. The current method consists of
      transplantation of both epidermal and dermal cells, using a silicone chamber
      placed on an athymic nude mouse. However, because of leakage and tilting of the
      grafted cells, the rate and area of hair growth vary depending on the chamber. We
      modified this method by using a collagen sponge as a scaffold and compared two
      types of collagen sponges, each having different tensile strengths. A
      conventional collagen sponge disturbed normal hair follicle formation; in
      contrast, a collagen sponge containing polyglycolic acid (PGA) fiber supported
      proper restructuring of skin and hair follicles. These data suggested the
      usefulness of PGA fiber-containing collagen sponges for hair reconstitution in
      research and clinical applications.

PMID- 15265300
TI  - Effect of low oxygen tension on tissue-engineered cartilage construct development
      in the concentric cylinder bioreactor.
AB  - Cartilage is exposed to low oxygen tension in vivo, suggesting culture in a low
      oxygen environment as a strategy to enhance matrix deposition in tissue
      engineered cartilage in vitro. To assess the effects of oxygen tension on
      cartilage matrix accumulation, porous polylactic acid constructs were dynamically
      seeded in a concentric cylinder bioreactor with bovine chondrocytes and cultured
      for 3 weeks at either 20 or 5% oxygen tension. Robust chondrocyte proliferation
      and matrix deposition were achieved. After 22 days in culture, constructs from
      bioreactors operated at either 20 or 5% oxygen saturation had similar chondrocyte
      densities and collagen content. During the first 12 days of culture, the matrix
      glycosaminoglycan (GAG) deposition rate was 19.5 x 10(-9) mg/cell per day at 5%
      oxygen tension and 65% greater than the matrix GAG deposition rate at 20% oxygen
      tension. After 22 days of bioreactor culture, constructs at 5% oxygen contained
      4.5 +/- 0.3 mg of GAG per construct, nearly double the 2.5 +/- 0.2 mg of GAG per
      construct at 20% oxygen tension. These data demonstrate that culture in
      bioreactors at low oxygen tension favors the production and retention of GAG
      within cartilage matrix without adversely affecting chondrocyte proliferation or
      collagen deposition. Bioreactor studies such as these can identify conditions
      that enhance matrix accumulation and construct development for cartilage tissue
      engineering.

PMID- 15265301
TI  - Tissue engineering using magnetite nanoparticles and magnetic force: heterotypic
      layers of cocultured hepatocytes and endothelial cells.
AB  - Novel technologies to establish three-dimensional, in vivo-like tissue consisting
      of various types of cells are required for tissue engineering. We applied
      magnetic force to construct a heterotypic, layered coculture system of rat
      hepatocytes and human aortic endothelial cells (HAECs) that was not limited by
      cell type. Magnetite cationic liposomes carrying a positive surface charge to
      improve adsorption accumulated in HAECs at a concentration of 38 pg of magnetite
      per cell. Magnetically labeled HAECs specifically accumulated onto hepatocyte
      monolayers at sites where a magnet (4000 G) was positioned, and then adhered to
      form a heterotypic, layered construct with tight and close contact. This
      cocultured construct significantly (p < 0.05) enhanced albumin secretion by
      hepatocytes compared with that in homotypic cultures of hepatocytes or
      heterotypic cocultures of hepatocytes and HAECs without magnets. These results
      suggest that this novel use of magnetite nanoparticles and magnetic force, which
      we refer to as "magnetic force-based tissue engineering" (Mag-TE), offers a major
      advancement in tissue engineering.

PMID- 15265302
TI  - Modulated fibronectin anchorage at polymer substrates controls angiogenesis.
AB  - A set of maleic anhydride copolymer thin films exhibiting well-defined
      differences in hydrophobicity and reactivity was compared with respect to the
      capability of supporting angiogenesis of human endothelial cells grown in
      contact. The physicochemical surface characteristics of the polymer substrates
      were found to modulate the anchorage of immobilized fibronectin. This was
      demonstrated to determine whether endothelial cells grow as a monolayer or form
      capillary networks. Enhanced reorganization of predeposited fibronectin into cell
      matrix adhesions and slightly elevated levels of membrane-type matrix
      metalloproteinase 14 (MMP-14) occurred with weakly bound fibronectin layers where
      angiogenesis was most obvious. The key role of fibronectin-substrate binding for
      angiogenesis-under otherwise constant conditions-was further confirmed by the
      absence of variations in the expression of angiogenesis-related integrins
      (alpha(v)beta(3)) and in the secretion of the metalloproteinase MMP-2.
      Altogether, the results of this study point at the relevance of physicochemical
      surface characteristics of polymer materials for the stimulation of angiogenesis.

PMID- 15265303
TI  - Transplantation of fetal cardiomyocytes into infarcted rat hearts results in long
      term functional improvement.
AB  - Studies have demonstrated the feasibility of transplanting cardiomyocytes after
      myocardial infarction (MI). However, persistence and effects on left ventricular
      (LV) function have not been elucidated in long-term studies. Ventricular fetal
      cardiomyocytes from embryos of both sexes were injected into marginal regions of
      MI 4 weeks after suture occlusion of the left anterior descending artery in adult
      female rats. Two and 6 months after transplantation (Tx), engrafted cells were
      traced by immunohistochemical in situ hybridization for Y chromosomes or
      bromodeoxyuridine (BrdU) staining, LV dimensions and function were assessed by
      echocardiography, and LV pressure was assessed ex vivo in a Langendorff perfusion
      system. Immunohistochemistry for alpha-sarcomeric actin and Y chromosomes
      revealed the presence of transplanted cells in infarcted host myocardium at both
      2 and 6 months. End-diastolic LV diameter markedly decreased after Tx and
      fractional shortening gradually increased after Tx (31.3 +/- 4.5% before Tx, 45.4
      +/- 4.2% at 6 months; p<0.005). Wall area fraction and MI size were unaffected by
      Tx. In hearts with MI, but not in normal hearts, Tx led to the development of
      higher pressures (87 +/- 18 versus 38 +/- 8 mmHg, 6 months post-Tx versus
      nontreated). After catecholamine stimulation, both infarcted and normal hearts
      developed higher pressures after Tx (p<0.005), ultimately associated with reduced
      mortality after Tx versus nontreated. Transplanted cardiomyocyte-rich graft cells
      persist in host myocardium and mediate continuous improvement of LV function and
      survival in a rat model of MI even during long-term follow-up, possibly involving
      a catecholamine-sensitive mechanism.

PMID- 15265304
TI  - Simple approach to micropattern cells on common culture substrates by tuning
      substrate wettability.
AB  - The ability to spatially control cell adhesion and multicellular organization is
      critical to many biomedical and tissue-engineering applications. This work
      describes a straightforward method to micropattern cells onto glass, silicone
      rubber, and polystyrene using commercially available reagents. An elastomeric
      polydimethylsiloxane stamp is used to contact-transfer extracellular matrix
      protein onto a surface followed by blocking cell adhesion in the surrounding
      regions by the physisorption of Pluronic surfactants. Using self-assembled
      monolayers of alkanethiols on gold as model surfaces to control surface
      wettability, we found that protein printing was most effective at intermediate to
      highly wetting surfaces whereas Pluronic adsorption occurred at intermediate to
      low wetting surfaces. Within a regimen of intermediate wettability both
      techniques were applied in conjunction to restrict cell adhesion to specified
      patterns. Adjusting the wettability of common tissue culture substrates to the
      same intermediate range again allowed the micropatterning of cells, suggesting
      that this approach is likely to be generally applicable to many types of
      materials. This technique therefore may allow for wider adoption of cell
      patterning.

PMID- 15265305
TI  - Construction and harvest of multilayered keratinocyte sheets using magnetite
      nanoparticles and magnetic force.
AB  - Novel technologies to establish three-dimensional constructs are desired for
      tissue engineering. In the present study, magnetic force was used to construct
      multilayered keratinocyte sheets and harvest the sheets without enzymatic
      treatment. Our original magnetite cationic liposomes, which have a positive
      surface charge in order to improve adsorption, were taken up by human
      keratinocytes at a concentration of 33 pg of magnetite per cell. The magnetically
      labeled keratinocytes (2x10(6) cells, which corresponds to 5 times the confluent
      concentration against the culture area of 24-well plates, in order to produce 5
      layered keratinocyte sheets) were seeded into a 24-well ultralow-attachment
      plate, the surface of which was composed of a covalently bound hydrogel layer
      that is hydrophilic and neutrally charged. A magnet (4000 G) was placed under the
      well, and the keratinocytes formed a five-layered construct in low-calcium medium
      (calcium concentration, 0.15 mM) after 24 h of culture. Subsequently, when the
      five-layered keratinocytes were cultured in high-calcium medium (calcium
      concentration, 1.0 mM), keratinocytes further stratified, resulting in the
      formation of 10-layered epidermal sheets. When the magnet was removed, the sheets
      were detached from the bottom of the plates, and the sheets could be harvested
      with a magnet. These results suggest that this novel methodology using magnetite
      nanoparticles and magnetic force, which we have termed "magnetic force-based
      tissue engineering" (Mag-TE), is a promising approach for tissue engineering.

PMID- 15265306
TI  - Acellular bovine pericardia with distinct porous structures fixed with genipin as
      an extracellular matrix.
AB  - A cell extraction process was employed to remove the cellular components from
      bovine pericardia. Various porous structures of the acellular tissues were then
      created, using acetic acid and collagenase, and subsequently fixed with genipin.
      The biological response and tissue regeneration pattern for each studied group
      were evaluated in a growing rat model. One month postoperatively, fibroblasts,
      neoconnective tissue fibrils, and neocapillaries were observed in the acellular,
      acetic acid-treated, and collagenase-treated tissues to fill the pores within the
      implanted samples, indicating that these tissue samples were being regenerated.
      The neoconnective tissue fibrils were identified to be neocollagen fibrils and
      neoglycosaminoglycans. On the other hand, no tissue regeneration was observed in
      the cellular tissue throughout the entire course of the study; tissue
      regeneration was limited to the outer most layer of the acellular tissue. In
      contrast, the areas of tissue regeneration in the acetic acid-treated and
      collagenase-treated tissues were expanded with increasing duration of
      implantation. However, 1 year postoperatively there were still numerous
      inflammatory cells observed in the acetic acid-treated tissue, whereas
      inflammatory cells in the collagenase-treated tissue had almost disappeared.
      These results indicated that tissue regeneration patterns within acellular
      tissues were significantly affected by their porous structures.

PMID- 15265307
TI  - Tissue engineering of ligaments: a comparison of bone marrow stromal cells,
      anterior cruciate ligament, and skin fibroblasts as cell source.
AB  - Anterior cruciate ligament (ACL) reconstruction surgery still has important
      problems to overcome, such as "donor site morbidity" and the limited choice of
      grafts in revision surgery. Tissue engineering of ligaments may provide a
      solution for these problems. Little is known about the optimal cell source for
      tissue engineering of ligaments. The aim of this study is to determine the
      optimal cell source for tissue engineering of the anterior cruciate ligament.
      Bone marrow stromal cells (BMSCs), ACL, and skin fibroblasts were seeded onto a
      resorbable suture material [poly(L-lactide/glycolide) multifilaments] at five
      different seeding densities, and cultured for up to 12 days. All cell types
      tested attached to the suture material, proliferated, and synthesized
      extracellular matrix rich in collagen type I. On day 12 the scaffolds seeded with
      BMSCs showed the highest DNA content (p < 0.01) and the highest collagen
      production (p < 0.05 for the two highest seeding densities). Scaffolds seeded
      with ACL fibroblasts showed the lowest DNA content and collagen production.
      Accordingly, BMSCs appear to be the most suitable cells for further study and
      development of tissue-engineered ligament.

PMID- 15265308
TI  - New tissue dissociation protocol for scaled-up production of neural stem cells in
      suspension bioreactors.
AB  - The successful dissociation of mammalian neural stem cell (NSC) aggregates
      (neurospheres) into a single-cell suspension is an important procedure when
      expanding NSCs for clinical use, or when performing important assays such as
      clonal analyses. Until now, researchers have had to rely primarily on destructive
      mechanical methods such as trituration with a pipette tip to break apart the
      aggregates. In this study we report on a new chemical dissociation procedure that
      is efficient, cost effective, reproducible, and much less harmful to murine NSCs
      than both mechanical and enzymatic techniques. This method, involving the
      manipulation of environmental pH levels, resulted in 40% higher measured cell
      densities and 15-20% higher viabilities compared with mechanical dissociation.
      Moreover, chemical dissociation resulted in the production of significantly less
      cellular debris. Chemical dissociation was found to have no adverse effects on
      the long-term proliferation of the NSCs, which retained the ability to
      proliferate, form neurospheres, self-renew, and exhibit multipotentiality. This
      chemical method represents a new approach for the dissociation of tissues.

PMID- 15265309
TI  - Characterization of murine autologous salivary gland graft cells: a model for use
      with an artificial salivary gland.
AB  - The purpose of this study was to examine the growth and key functional abilities
      of primary cultures of salivary epithelial cells toward developing an artificial
      salivary gland. Cultures of epithelial cells originating from submandibular
      glands of BALB/c mice were established. Parenchymal cells were isolated by a
      Percoll gradient technique and thereafter seeded on irradiated NIH 3T3
      fibroblasts serving as a feeder layer. The isolated cells were termed autologous
      salivary gland epithelial (ASGE) cells and could be cultivated for at least five
      passages (time limit of experiments). ASGE cells presented the typical
      organizational behavior of epithelial cells and electron microscopy, as well as
      immunostaining for cytokeratins, confirmed their epithelial origin. Furthermore,
      measurements of transepithelial resistance and water permeability indicated the
      ability of the ASGE cells to form a functional epithelial barrier. This study
      suggests that primary salivary epithelial cells can be obtained that exhibit
      critical characteristics needed for use with an artificial secretory device.

PMID- 15265310
TI  - Ultrasound enhances transforming growth factor beta-mediated chondrocyte
      differentiation of human mesenchymal stem cells.
AB  - In clinical studies and animal models, low-intensity ultrasound (US) promotes
      fracture repair and increases mechanical strength. US also promotes cartilage
      healing by increasing glycosaminoglycan synthesis of chondrocytes. As mesenchymal
      stem cells (MSCs) have the ability to differentiate into chondrocytes, US may
      promote their differentiation. Here, we evaluated the effects of US on the
      differentiation of MSCs toward chondrocytes and cartilage matrix formation. When
      human MSCs cultured in pellets were treated with transforming growth factor beta
      (TGF-beta, 10 ng/mL), they differentiated into chondrocytes as assessed by alcian
      blue staining and immunostaining for aggrecan, but nontreated cell pellets did
      not. Furthermore, when low-intensity US was applied for 20 min every day to the
      TGF-beta-treated cell pellets, chondrocyte differentiation was enhanced.
      Biochemically, aggrecan deposition was increased by 2.9- and 8.7-fold by
      treatment with TGF-beta alone, and with both TGF-beta and US, respectively. In
      contrast, cell proliferation and total protein amount appeared unaffected by
      these treatments. These results indicate that low-intensity US enhances TGF-beta
      mediated chondrocyte differentiation of MSCs in pellet culture and that
      application of US may facilitate larger preparations of chondrocytes and the
      formation of mature cartilage tissue.

PMID- 15265311
TI  - Perfusion bioreactor for small diameter tissue-engineered arteries.
AB  - A scaleable perfusion bioreactor has been developed for tissue engineering of
      small diameter arterial constructs. This modular bioreactor allows for dynamic
      sequential seeding of smooth muscle and endothelial cells, biomechanical
      stimulation of cells during culture, and monitoring of tissue growth and
      maturation. Bovine aortic smooth muscle and endothelial cells were seeded onto
      porous tubular poly(glycolic acid) nonwoven scaffolds and cultured in the
      bioreactor under pulsatile flow conditions for up to 25 days. Cell proliferation
      was more than 3-fold after 4 days, smooth muscle cells expressed differentiated
      phenotype after 16 days, and collagen and elastin were distributed throughout the
      construct after 25 days of culture. In bioreactor experiments in which the
      construct lumen was seeded with endothelial cells by perfusion after 13 days of
      smooth muscle cell culture, endothelial cell seeding efficiency was 100%, and a
      confluent monolayer was observed in the lumen within 48 h. These data demonstrate
      that this perfusion bioreactor supports sequential seeding of constructs with
      smooth muscle and endothelial cells. Dynamic culture under pulsatile flow leads
      to cellular expression of differentiated function and extracellular matrix
      deposition toward the development of tissue-engineered arterial constructs.

PMID- 15265312
TI  - Behavior of human dermal fibroblasts in three-dimensional fibrin clots:
      dependence on fibrinogen and thrombin concentration.
AB  - Fibrin sealant products are used in hemostasis and tissue sealing, and
      potentially as a cell delivery vehicle. In this study, fibrin sealant was
      evaluated as a delivery vehicle for human dermal fibroblasts. Fibroblast
      proliferation and migration were assessed in various dilutions of fibrin sealant
      by changing the fibrinogen and thrombin concentration. Fibroblasts proliferated
      well within three-dimensional (3-D) fibrin clots consisting of fibrinogen (5-17
      mg/mL) and thrombin (1-167 U/mL). These fibroblasts also retained good morphology
      and growth characteristics after migrating out of the 3-D fibrin clots.
      Furthermore, using Western blot and fluorescence-activated cell-sorting analysis,
      we found that the expression of growth factors and interleukins in the entire
      fibroblast-fibrin construct was dependent on the fibrin sealant formulation. For
      example, in a formulation in which fibroblasts showed modest proliferation and
      migration, interleukin 8 was secreted to a lesser extent than in a formulation
      that supported robust proliferation and migration. To our knowledge, this is the
      first time that it has been shown that modifying the concentration of fibrinogen
      and thrombin affects fibroblast behavior within formed 3-D fibrin clots. In
      addition, some of these formulations present an ideal delivery vehicle for
      fibroblasts that could be used for the treatment of chronic wounds.

PMID- 15265313
TI  - Autogenous injectable bone for regeneration with mesenchymal stem cells and
      platelet-rich plasma: tissue-engineered bone regeneration.
AB  - We have attempted to regenerate bone in a significant osseous defect with minimal
      invasiveness and good plasticity, and to provide a clinical alternative to
      autogenous bone grafts. Platelet-rich plasma (PRP) may enhance the formation of
      new bone and is nontoxic, nonimmunoreactive, and accelerates existing wound
      healing pathways. We have used a combination of PRP as an autologous scaffold
      with in vitro-expanded mesenchymal stem cells (MSCs) to increase osteogenesis,
      compared with using the scaffold alone or autogenous particulate cancellous bone
      and marrow (PCBM). The newly formed bones were evaluated by radiography,
      histology, and histomorphometric analysis in the defects at 2, 4, and 8 weeks.
      According to the histological observations, the dog MSCs (dMSCs)/PRP group had
      well-formed mature bone and neovascularization compared with the control (defect
      only), PRP, and PCBM groups at 2 and 4 weeks. Histometrically, at 8 weeks newly
      formed bone areas were 18.3 +/- 4.84% (control), 29.2 +/- 5.47% (PRP), 61.4 +/-
      3.38% (PCBM), and 67.3 +/- 2.06% (dMSCs/PRP). There were significant differences
      between the PCBM, dMSCs/PRP, and control groups. These results demonstrate that
      the dMSCs/PRP mixture is useful as a osteogenic bone substitute.

PMID- 15265314
TI  - Cannabinoids in pain and inflammation.
AB  - Cannabinoids exhibit medicinal properties including analgesic, anti-inflammatory
      and immunosuppressive properties. This paper reviews some of the recent findings
      in the study of cannabinoids in pain and inflammation. Some of the effects of
      cannabinoids are receptor mediated and others are receptor independent.
      Endocannabinoids naturally reduce pain and are cerebroprotective. Natural and
      synthetic cannabinoids have the potential to reduce nociception, reverse the
      development of allodynia and hyperalgesia, reduce inflammation and inflammatory
      pain and protect from secondary tissue damage in traumatic head injury.

PMID- 15265315
TI  - Protective effects of lysozyme chloride and reduced glutathione on betel quid
      chewing-produced gastric oxidative stress and haemorrhagic ulcer in rats.
AB  - The pathogenic mechanisms underlying betel quid chewing (BQC)-induced gastric
      haemorrhagic ulcer are totally unknown. This study first demonstrated that BQC
      produced gastric haemorrhagic ulcer via oxidative stress that could be protected
      by lysozyme chloride and glutathione in rats. Male Wistar rats were fed with
      regular pellet food or BQC-containing diets. After 1-90 days rats were deprived
      of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or
      simulated gastric juice. Rats were killed and gastric specimens were harvested. A
      BQC-feeding period-dependent exacerbation of gastric parameters, such as enhanced
      acid back-diffusion, mucosal lipid peroxide generation, as well as related
      decreased glutathione levels and mucus content, were observed. Gastric juice
      caused a further aggravation of these ulcerogenic parameters. Daily intragastric
      lysozyme chloride or glutathione dose-dependently inhibited exacerbation of
      various ulcerogenic parameters in those BQC-fed rats. In conclusion, BQC can
      produce gastric haemorrhagic ulcer in rats via oxidative stress that could be
      ameliorated by lysozyme chloride and glutathione.

PMID- 15265316
TI  - Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent
      atherosclerosis.
AB  - BHUx is a polyherbal formulation consisting of water-soluble fractions of five
      medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata,
      Semecarpus anacardium and Strychnos nux vomica). The present study was undertaken
      to evaluate its antioxidant and antiinflammatory effects. BHUx, standardized by
      HPLC fingerprinting and filtered through 0.2 microm filter paper, was employed
      for different studies under in vivo and in vitro conditions. Under in vivo
      conditions, BHUx significantly reduced inflammation in the carrageenan-induced
      rat paw oedema model of inflammation, suggesting its anti-inflammatory
      properties. In order to test the mechanism of action of BHUx, further in vitro
      studies were undertaken on cumene-hydroperoxide-induced lipid peroxidation (CHP)
      in liver homogenate, LPS-induced NO production in peritoneal macrophages and on
      key enzymes of arachidonic acid cascade, involved in the mediation of
      inflammation. Under the conditions, BHUx showed concentration-dependent
      inhibition of CHP-induced lipid peroxidation in liver homogenate, suggesting its
      antioxidant properties. Similarly the potent anti-inflammatory effects of BHUx
      are evident by (a) preferential inhibition of COX-2 (IC50 for COX-2 = 80
      microg/ml and IC50 for COX-1 = 169 microg/ml), (b) low ratios in the IC50 values
      of COX-2/COX-1 (0.47), (c) decreased production of NO in LPS-induced peritoneal
      macrophages and (d) inhibition of 5-LOX (IC50 = 795 microg/ml). BHUx also showed
      a preference for inhibiting 15-lipoxygenase (IC50 = 44 microg/ml), a key enzyme
      implicated in LDL oxidation. These studies suggest that BHUx is acting mainly at
      three levels, i.e., as a potent natural antioxidant, by reduction of key
      inflammatory mediators of arachidonic acid cascade and by preventing 15-LOX
      mediated LDL oxidations, to prevent atherosclerosis.

PMID- 15265317
TI  - Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect
      on H+-K+-ATPase, oxidative damage and apoptosis.
AB  - The mechanism of the antiulcer effect of Neem leaf aqueous extract to block
      gastric lesions in rat has been studied with emphasis on acid secretion,
      oxidative damage and apoptosis. The extract dose-dependently inhibits gastric
      lesions induced by restraint-cold stress, indomethacin and ethanol. In stress
      ulcer model, it is more effective than ranitidine but less effective than
      omeprazole. It also dose-dependently blocks pylorus ligation and
      mercaptomethylimidazole-induced acid secretion. In the pylorus-ligation model, it
      is less effective than omeprazole but as effective as ranitidine. It inhibits H+
      K+-ATPase activity in vitro in concentration-dependent manner to inhibit acid
      secretion. Oxidative membrane damage by hydroxyl radical (*OH) as measured by
      lipid peroxidation in stress ulcer is significantly blocked by leaf extract.
      Stress-induced apoptotic DNA fragmentation is also protected. The extract also
      prevents *OH-mediated mucosal DNA damage in vitro by scavenging the *OH. Neem
      leaf extract, thus, offers antiulcer activity by blocking acid secretion through
      inhibition of H+-K+-ATPase and by preventing oxidative damage and apoptosis.

PMID- 15265318
TI  - Role of epidermal growth factor receptor transactivation in PPAR gamma-dependent
      suppression of Helicobacter pylori interference with gastric mucin synthesis.
AB  - Peroxisome-proliferator-activated receptor gamma (PPARgamma) is recognized for
      its role in regulation of genes associated with inflammation, and its activation
      of phosphatidylinositol 3-kinase (PI3K) has emerged recently as an important
      regulator of mucosal responses to bacterial infection. In this study, we report
      that PPARgamma activation leading to the impedance of Helicobacter pylori
      lipopolysaccharide (LPS) inhibitory effect on salivary mucin synthesis requires
      epidermal growth factor receptor (EGFR) participation. Using gastric mucosal
      cells in culture, we show that activation of PPARgamma with a specific agonist,
      ciglitazone, prevents the LPS-induced reduction in mucin synthesis, and the
      effect is reflected in a marked decrease in apoptosis, caspase-3 activity and NO
      generation. The impedance by ciglitazone of the LPS-induced reduction in mucin
      synthesis was blunted (up to 65.8%) in a concentration-dependent fashion by a
      specific inhibitor of EGFR kinase, PD153035, as well as the PPARgamma antagonist
      BADGE, and wortmannin, an inhibitor of PI3K. Moreover, the inhibitory effect of
      ciglitazone on the LPS-induced reduction in mucin synthesis and upregulation in
      apoptosis, caspase-3 activity and NO generation was countered by PP2, a selective
      inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR
      transactivation. These findings indicate that PPARgamma activation leading to the
      suppression of H. pylori LPS inhibition of gastric mucin synthesis involves Src
      kinase-dependent EGFR transactivation.

PMID- 15265319
TI  - Effect of zileuton in radicular pain induced by herniated nucleus pulposus in
      rats.
AB  - Arachidonic acid metabolites, prostaglandins and leukotrienes are detected in
      clinical cases of herniated nucleus pulposus. However, little is known about
      their role in the associated symptoms like radicular pain. The aim of the present
      study was to examine the role of leukotrienes in an animal model of hyperalgesia
      induced by application of autologus nucleus pulposus to sciatic nerve in rats.
      Hyperalgesia was assessed employing noxious mechanical and thermal stimuli.
      Zileuton, a 5-lipoxygenase inhibitor, dose dependently (25-100 mg/kg, p.o.), and
      indomethacin (2 mg/kg, p.o.), a non-selective cyclooxygenase inhibitor,
      significantly (P > 0.05) decreased mechanical as well as thermal hyperalgesia on
      postoperative days 3, 5 and 7 as compared to the nucleus pulposus group. Further,
      co-administration of zileuton (25 mg/kg, p.o.) with indomethacin (2 mg/kg, p.o.)
      showed enhanced anti-hyperalgesic effect in both the paradigms as compared to
      effect per se. The present study, thus, suggested that leukotrienes as well as
      prostaglandins might play a significant role in hyperalgesia induced by autologus
      nucleus pulposus in rats. The results suggested that dual inhibition approach of
      5-lipoxygenase and cyclooxygenase enzymes may prove beneficial in such
      conditions.

PMID- 15265320
TI  - Anti-inflammatory studies on Adenanthera pavonina seed extract.
AB  - A methanol extract of the seeds of Adenanthera pavonina was evaluated for
      pharmacological effects in animal models. The extract (50-200 mg/kg) produced
      statistically significant (P < 0.05) inhibition of the carrageenan-induced paw
      oedema in the rat, as well as the acetic-acid-induced vascular permeability in
      mice. At doses of 100 and 200 mg/kg, pleurisy induced with carrageenan was also
      inhibited. The extract (50-200 mg/kg) exhibited a dose-dependent and significant
      (P < 0.05) analgesic activity in the acetic-induced writhing in mice. In
      addition, both early and late phases of the formalin-induced paw licking in mice
      was inhibited by the extract. Acute toxicity studies revealed that the extract
      produced reduced motor activity. The LD50 value of the extract was found to be
      1.36 g/kg. This study demonstrated the anti-inflammatory and analgesic effects of
      A. pavonina extract.

PMID- 15265321
TI  - Anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in
      combination with cimetidine.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the
      modulation of the inflammatory response. However, a number of facts involving the
      occurrence of gastrointestinal lesions have limited the chronic use of NSAIDs. In
      order to diminish the occurrence of gastrointestinal damage caused by NSAIDs, the
      combination of NSAIDs with the H2 receptor blocker, cimetidine, has been
      evaluated. The anti-inflammatory and ulcerogenic effects of indomethacin and
      tenoxicam in association with or without cimetidine were determined at pre
      clinical levels. It was observed that the group of animals treated with
      indomethacin and cimetidine, or tenoxicam and cimetidine (10 mg/kg, p.o.)
      demonstrated a significant reduction (P < 0.05, ANOVA followed by Tukey-Kramer
      multiple comparison test) of type-III gastric ulcers. Furthermore, indomethacin
      or tenoxicam (10 mg/kg, p.o.) in association with cimetidine increased the anti
      inflammatory activity. The group, which received indomethacin and cimetidine
      presented the best performance in decreasing the inflammatory process (P < 0.05,
      ANOVA followed by Tukey-Kramer multiple comparison test).

PMID- 15265322
TI  - Stochastic reasoning, free energy, and information geometry.
AB  - Belief propagation (BP) is a universal method of stochastic reasoning. It gives
      exact inference for stochastic models with tree interactions and works
      surprisingly well even if the models have loopy interactions. Its performance has
      been analyzed separately in many fields, such as AI, statistical physics,
      information theory, and information geometry. This article gives a unified
      framework for understanding BP and related methods and summarizes the results
      obtained in many fields. In particular, BP and its variants, including tree
      reparameterization and concave-convex procedure, are reformulated with
      information-geometrical terms, and their relations to the free energy function
      are elucidated from an information-geometrical viewpoint. We then propose a
      family of new algorithms. The stabilities of the algorithms are analyzed, and
      methods to accelerate them are investigated.

PMID- 15265323
TI  - Blind separation of positive sources by globally convergent gradient search.
AB  - The instantaneous noise-free linear mixing model in independent component
      analysis is largely a solved problem under the usual assumption of independent
      nongaussian sources and full column rank mixing matrix. However, with some prior
      information on the sources, like positivity, new analysis and perhaps simplified
      solution methods may yet become possible. In this letter, we consider the task of
      independent component analysis when the independent sources are known to be
      nonnegative and well grounded, which means that they have a nonzero pdf in the
      region of zero. It can be shown that in this case, the solution method is
      basically very simple: an orthogonal rotation of the whitened observation vector
      into nonnegative outputs will give a positive permutation of the original
      sources. We propose a cost function whose minimum coincides with nonnegativity
      and derive the gradient algorithm under the whitening constraint, under which the
      separating matrix is orthogonal. We further prove that in the Stiefel manifold of
      orthogonal matrices, the cost function is a Lyapunov function for the matrix
      gradient flow, implying global convergence. Thus, this algorithm is guaranteed to
      find the nonnegative well-grounded independent sources. The analysis is
      complemented by a numerical simulation, which illustrates the algorithm.

PMID- 15265324
TI  - A new concept for separability problems in blind source separation.
AB  - The goal of blind source separation (BSS) lies in recovering the original
      independent sources of a mixed random vector without knowing the mixing
      structure. A key ingredient for performing BSS successfully is to know the
      indeterminacies of the problem-that is, to know how the separating model relates
      to the original mixing model (separability). For linear BSS, Comon (1994) showed
      using the Darmois-Skitovitch theorem that the linear mixing matrix can be found
      except for permutation and scaling. In this work, a much simpler, direct proof
      for linear separability is given. The idea is based on the fact that a random
      vector is independent if and only if the Hessian of its logarithmic density
      (resp. characteristic function) is diagonal everywhere. This property is then
      exploited to propose a new algorithm for performing BSS. Furthermore, first ideas
      of how to generalize separability results based on Hessian diagonalization to
      more complicated nonlinear models are studied in the setting of postnonlinear
      BSS.

PMID- 15265325
TI  - Modeling mental navigation in scenes with multiple objects.
AB  - Various lines of evidence indicate that animals process spatial information
      regarding object locations differently from spatial information regarding
      environmental boundaries or landmarks. Following Wang and Spelke's (2002)
      observation that spatial updating of egocentric representations appears to lie at
      the heart of many navigational tasks in many species, including humans, we
      postulate a neural circuit that can support this computation in parietal cortex,
      assuming that egocentric representations of multiple objects can be maintained in
      prefrontal cortex in spatial working memory (not simulated here). Our method is a
      generalization of an earlier model by Droulez and Berthoz (1991), with extensions
      to support observer rotation. We can thereby simulate perspective transformation
      of working memory representations of object coordinates based on an egomotion
      signal presumed to be generated via mental navigation. This biologically
      plausible transformation would allow a subject to recall the locations of
      previously viewed objects from novel viewpoints reached via imagined,
      discontinuous, or disoriented displacement. Finally, we discuss how this model
      can account for a wide range of experimental findings regarding memory for object
      locations, and we present several predictions made by the model.

PMID- 15265326
TI  - Failure of motor learning for large initial errors.
AB  - For certain complex motor tasks, humans may experience the frustration of a lack
      of improvement despite repeated practice. We investigate a computational basis
      for failure of motor learning when there is no prior information about the system
      to be controlled and when it is not practical to perform a thorough random
      exploration of the set of possible commands. In this case, if the desired
      movement has never yet been performed, then it may not be possible to learn the
      correct motor commands since there will be no appropriate training examples. We
      derive the mathematical basis for this phenomenon when the controller can be
      modeled as a linear combination of nonlinear basis functions trained using a
      gradient descent learning rule on the observed commands and their results. We
      show that there are two failure modes for which continued training examples will
      never lead to improvement in performance. We suggest that this may provide a
      model for the lack of improvement in human skills that can occur despite repeated
      practice of a complex task.

PMID- 15265327
TI  - Fair attribution of functional contribution in artificial and biological
      networks.
AB  - This letter presents the multi-perturbation Shapley value analysis (MSA), an
      axiomatic, scalable, and rigorous method for deducing causal function
      localization from multiple perturbations data. The MSA, based on fundamental
      concepts from game theory, accurately quantifies the contributions of network
      elements and their interactions, overcoming several shortcomings of previous
      function localization approaches. Its successful operation is demonstrated in
      both the analysis of a neurophysiological model and of reversible deactivation
      data. The MSA has a wide range of potential applications, including the analysis
      of reversible deactivation experiments, neuronal laser ablations, and
      transcranial magnetic stimulation "virtual lesions," as well as in providing
      insight into the inner workings of computational models of neurophysiological
      systems.

PMID- 15265328
TI  - Recurrent network with large representational capacity.
AB  - A recurrent network is proposed with the ability to bind image features into a
      unified surface representation within a single layer and without capacity
      limitations or border effects. A group of cells belonging to the same object or
      surface is labeled with the same activity amplitude, while cells in different
      groups are kept segregated due to lateral inhibition. Labeling is achieved by
      activity spreading through local excitatory connections. In order to prevent
      uncontrolled spreading, a separate network computes the intensity difference
      between neighboring locations and signals the presence of the surface boundary,
      which constrains local excitation. The quality of surface representation is not
      compromised due to the self-excitation. The model is also applied on gray-level
      images. In order to remove small, noisy regions, a feedforward network is
      proposed that computes the size of surfaces. Size estimation is based on the
      difference of dendritic inhibition in lateral excitatory and inhibitory pathways,
      which allows the network to selectively integrate signals only from cells with
      the same activity amplitude. When the output of the size estimation network is
      combined with the recurrent network, good segmentation results are obtained. Both
      networks are based on biophysically realistic mechanisms such as dendritic
      inhibition and multiplicative integration among different dendritic branches.

PMID- 15265329
TI  - A solution for two-dimensional mazes with use of chaotic dynamics in a recurrent
      neural network model.
AB  - Chaotic dynamics introduced into a neural network model is applied to solving two
      dimensional mazes, which are ill-posed problems. A moving object moves from the
      position at t to t + 1 by simply defined motion function calculated from firing
      patterns of the neural network model at each time step t. We have embedded
      several prototype attractors that correspond to the simple motion of the object
      orienting toward several directions in two-dimensional space in our neural
      network model. Introducing chaotic dynamics into the network gives outputs
      sampled from intermediate state points between embedded attractors in a state
      space, and these dynamics enable the object to move in various directions. System
      parameter switching between a chaotic and an attractor regime in the state space
      of the neural network enables the object to move to a set target in a two
      dimensional maze. Results of computer simulations show that the success rate for
      this method over 300 trials is higher than that of random walk. To investigate
      why the proposed method gives better performance, we calculate and discuss
      statistical data with respect to dynamical structure.

PMID- 15265330
TI  - Online adaptive decision trees.
AB  - Decision trees and neural networks are widely used tools for pattern
      classification. Decision trees provide highly localized representation, whereas
      neural networks provide a distributed but compact representation of the decision
      space. Decision trees cannot be induced in the online mode, and they are not
      adaptive to changing environment, whereas neural networks are inherently capable
      of online learning and adpativity. Here we provide a classification scheme called
      online adaptive decision trees (OADT), which is a tree-structured network like
      the decision trees and capable of online learning like neural networks. A new
      objective measure is derived for supervised learning with OADT. Experimental
      results validate the effectiveness of the proposed classification scheme. Also,
      with certain real-life data sets, we find that OADT performs better than two
      widely used models: the hierarchical mixture of experts and multilayer
      perceptron.

PMID- 15265333
TI  - Acute mountain sickness: controversies and advances.
AB  - This review discusses the impact of recent publications on pathophysiologic
      concepts and on practical aspects of acute mountain sickness (AMS). Magnetic
      resonance imaging studies do not provide evidence of total brain volume increase
      nor edema within the first 6 to 10 h of exposure to hypoxia despite symptoms of
      AMS. After 16 to 32 h at about 4500 m, brain volume increases by 0.8% to 2.7%,
      but morphological changes do not clearly correlate with symptoms of AMS, and
      lumbar cerebrospinal fluid pressure was unchanged from normoxic values in
      individuals with AMS. These data do not support the prevailing hypothesis that
      AMS is caused by cerebral edema and increased intracranial pressure. Direct
      measurement of increased oxygen radicals in hypoxia and a first study reducing
      AMS when lowering oxygen radicals by antioxidants suggest that oxidative stress
      is involved in the pathophysiology of AMS. Placebo-controlled trials demonstrate
      that theophylline significantly attenuates periodic breathing without improving
      arterial oxygen saturation during sleep. Its effects on AMS are marginal and
      clearly inferior to acetazolamide. A most recent large trial with Ginkgo biloba
      clearly showed that this drug does not prevent AMS in a low-risk setting in which
      acetazolamide in a low dose of 2 x 125 mg was effective. Therefore, acetazolamide
      remains the drug of choice for prevention and the recommended dose remains 2 x
      250 mg daily until a lower dose has been tested in a high-risk setting and larger
      clinical trials with antioxidants have been performed.

PMID- 15265334
TI  - Unraveling the mechanism of high altitude pulmonary edema.
AB  - During the last decade, major advances in the understanding of the mechanism of
      high altitude pulmonary edema (HAPE) have supplemented the landmark work done in
      the previous 30 years. A brief review of the earlier studies will be described,
      which will then be followed by a more complete treatise on the subsequent
      research, which has elucidated the role of accentuated pulmonary hypertension in
      the development of HAPE. Vasoactive mediators, such as nitric oxide (NO) and
      endothelin-1, have played a major role in this understanding and have led to
      preventive and therapeutic interventions. Additionally, the role of the alveolar
      epithelium and the Na-K ATPase pump in alveolar fluid clearance has also more
      recently been understood. Direction for future work will be given as well.

PMID- 15265335
TI  - High altitude cerebral edema.
AB  - This review focuses on the epidemiology, clinical description, pathophysiology,
      treatment, and prevention of high altitude cerebral edema (HACE). HACE is an
      uncommon and sometimes fatal complication of traveling too high, too fast to high
      altitudes. HACE is distinguished by disturbances of consciousness that may
      progress to deep coma, psychiatric changes of varying degree, confusion, and
      ataxia of gait. It is most often a complication of acute mountain sickness or
      high altitude pulmonary edema. The current leading theory of its pathophysiology
      is that HACE is a vasogenic edema; that is, a disruption of the blood-brain
      barrier, and we review possible mechanisms to explain this. Treatment and
      prevention of HACE are similar to those for the other altitude illnesses, but
      with greater emphasis on descent and steroids. We conclude the review with
      several case histories to illustrate key clinical features of the disorder.

PMID- 15265336
TI  - Chronic mountain sickness: recent studies of the relationship between hemoglobin
      concentration and oxygen transport.
AB  - Although an increase in hemoglobin concentration [Hb] in high altitude residents
      assists oxygen transport, excessive polycythemia ([Hb] > or = 21 g/100 mL) may
      cause the syndrome of chronic mountain sickness (CMS). A recent theoretical
      analysis has suggested that increasing [Hb] above 18 g/100 mL provides no further
      benefit in oxygen transport at rest. To test this hypothesis, we examined oxygen
      transport at rest for given arterial oxygen saturations (Sa(O2), in classes at
      intervals of 5%) as reported in 206 residents of various altitudes. For Sa(O2) of
      97% versus 87%, [Hb] and a-v oxygen content difference increased (respectively,
      14.5 to 17.5 g/100 mL and 4.11 to 5.03 volume %). As Sa(O2) fell further to 66%,
      a-v progressively decreased to 3.77 volume %, despite an increase in [Hb] to 24.2
      g/100 mL. Over the Sa(O2) range of 97% to 66%, the a-v difference changed little
      (-8%) compared to other subjects made acutely hypoxic (-33%), for Sa(O2) change
      from 97% to 75%. The results suggest that increasing [Hb] allows greater oxygen
      extraction (a cardiac output sparing effect), which is maximal at Sa(O2) of 87%
      and a [Hb] of 17.5 g/100 mL. For more severe hypoxemia, even to Sa(O2) of 66%,
      both increasing [Hb] and increasing output are utilized for oxygen transport.

PMID- 15265337
TI  - Syndromes of subacute mountain sickness.
AB  - Two clinical syndromes, acute and chronic mountain sickness, have traditionally
      been associated with high altitude. Recently, two separate entities of subacute
      nature have been described in infants and adults. In this paper, we review the
      published literature on these conditions. Subacute infantile mountain sickness is
      a condition seen predominantly in Han Chinese infants living in Tibet, although
      it has been described in other high altitude communities as well. It came into
      prominence only after the large-scale migration of Chinese population from the
      low altitude of mainland China to the high altitudes of the Qinghai-Tibetan
      plateau. The condition is characterized by features of severe hypoxic pulmonary
      hypertension and heart failure. Pulmonary histology is consistent with
      muscularization of the pulmonary arterioles, but no intimal proliferation or
      plexiform lesions are seen. The second syndrome, adult subacute mountain
      sickness, has been described almost exclusively in Indian soldiers living at
      extreme altitude for prolonged periods of time. In this condition also, hypoxic
      pulmonary hypertension appears to be the dominant factor responsible for severe
      congestive heart failure. Both these conditions have several similarities with
      brisket disease in cattle; hypoxic pulmonary vasoconstriction plays an important
      role in the pathogenesis, and removal from high altitude results in complete
      resolution. Thus, it appears that both these syndromes are human counterparts of
      brisket disease in cattle.

PMID- 15265338
TI  - Neurological conditions at altitude that fall outside the usual definition of
      altitude sickness.
AB  - Altitude sickness in its commonly recognized forms consists of acute mountain
      sickness and the two life-threatening forms, high altitude cerebral and pulmonary
      edema. Less well known are other conditions, chiefly neurological, that may arise
      completely outside the usual definition of altitude sickness. These, often focal,
      neurological conditions are important to recognize so that they do not become
      categorized as altitude sickness because, besides oxygen and descent, treatment
      may be vastly different. Transient ischemic attacks, cerebral venous thrombosis,
      seizures, syncope, double vision, and scotomas are some of the well-documented
      neurological disturbances at high altitude discussed here in order to enhance
      their recognition and treatment.

PMID- 15265339
TI  - Sleep at high altitude.
AB  - New arrivals to altitude commonly experience poor-quality sleep. These complaints
      are associated with increased fragmentation of sleep by frequent brief arousals,
      which are in turn linked to periodic breathing. Changes in sleep architecture
      include a shift toward lighter sleep stages, with marked decrements in slow-wave
      sleep and with variable decreases in rapid eye movement (REM) sleep. Respiratory
      periodicity at altitude reflects alternating respiratory stimulation by hypoxia
      and subsequent inhibition by hyperventilation-induced hypocapnia. Increased
      hypoxic ventilatory responsiveness and loss of regularization of breathing during
      sleep contribute to the occurrence of periodicity. Interventions that improve
      sleep quality at high altitude include acetazolamide and benzodiazepines.

PMID- 15265340
TI  - A Tibetan with chronic mountain sickness followed by high altitude pulmonary
      edema on reentry.
AB  - Chronic mountain sickness (CMS) and high altitude pulmonary edema (HAPE) each
      occur rarely in Tibetans, and they have previously not been reported in the same
      person. Here we describe a 37-year-old native Tibetan man with CMS at 4300 m, who
      developed HAPE after his return home from a 12-day visit to sea level. Possible
      common pathogenetic factors included a poor ventilatory response to hypoxia,
      accentuated hypoxemia, pulmonary hypertension, and increased blood volume. In
      addition, strenuous exercise and high levels (to approximately 1000 ng/L) of
      plasma atrial natriuretic peptide may have contributed to HAPE.

PMID- 15265341
TI  - Lactate metabolism at high altitude.

PMID- 15265343
TI  - Progress in pain management: is the emperor dressed?

PMID- 15265344
TI  - Trying trials.

PMID- 15265345
TI  - Working to improve palliative care trials.

PMID- 15265346
TI  - Challenges for palliative care research.

PMID- 15265347
TI  - Mixed methods: in search of truth in palliative care medicine.

PMID- 15265348
TI  - Challenges in palliative care research: one experience.

PMID- 15265349
TI  - Palliative care research: the need to construct paradigms.

PMID- 15265350
TI  - Barriers to hospice care and referrals: survey of physicians' knowledge,
      attitudes, and perceptions in a health maintenance organization.
AB  - INTRODUCTION: Many proponents of hospice care believe that this service is
      underutilized. OBJECTIVE: To determine physicians' perceptions of hospice
      utilization and of their own hospice referral pattern; their perceived and actual
      knowledge of appropriate hospice referral diagnoses; and perceived barriers to
      hospice referral. METHODS: Surveys for anonymous response were distributed to 125
      physicians in 2 internal medicine departments of a large not-for-profit health
      maintenance organization (HMO). Of these 125 physicians, 89% responded, including
      91 staff physicians and 20 residents. RESULTS: Of the 111 physician-respondents,
      78% reported their belief that hospice care was underutilized; 84% were unable to
      identify appropriate hospice diagnoses; and 12% were aware of the "National
      Hospice Organization Medical Guidelines for Determining Prognosis in Selected Non
      Cancer Diseases." Difficulty of predicting death to within 6 months was cited by
      37% as the foremost barrier to hospice referral. In addition, 28% expressed
      concern that patients or families would interpret hospice referral as a cost
      saving measure; 11% of respondents had been accused of using hospice referral for
      this purpose. CONCLUSION: Our study-the first major survey of physician attitudes
      and practices regarding hospice utilization in an HMO setting-showed that
      barriers to hospice referral are similar to those in non-HMO settings; physicians
      have difficulty predicting life expectancy and lack knowledge of patient
      eligibility guidelines. Physician concern that patients or their family members
      would construe hospice referral as a cost-saving technique may be a barrier
      particularly troublesome in an HMO setting.

PMID- 15265351
TI  - Opioid rotation in children with cancer.
AB  - The purpose of this retrospective study was to determine the therapeutic value of
      opioid rotation in a large pediatric oncology center. The details for opioid
      prescriptions, over the course of a year, were obtained from the medical records
      of children with cancer who had a rotation of opioid during their admission.
      Twenty-two children or 14% of children on opioid therapy underwent 30 opioid
      rotations. Mucositis was the cause of pain in 19 (70%) children, bone pain in 3
      (11%) children, and postoperative, visceral, or neuropathic pain in the
      remainder. The opioid was rotated either for excessive side effects with adequate
      analgesia (70%), excessive side effects with inadequate analgesia (16.7%), or
      tolerance (6.7%). Five (23%) children required two rotations, 3 during the same
      admission. The favored rotations were morphine to fentanyl in 20 (67%) children
      and fentanyl to hydromorphone in 6 (20%). Adverse opioid effects were resolved in
      90% of cases, all failures occurred when morphine was rotated to fentanyl. There
      was no significant loss of pain control or increase in mean morphine equivalent
      dose requirements. Opioid rotation had a positive impact on managing dose
      limiting side effects of, or tolerance to, opioid therapy during cancer pain
      treatment in children. This was accomplished without loss of pain control or
      having to significantly increase the dose of opioid therapy.

PMID- 15265352
TI  - Appropriate methods to assess the effectiveness and efficacy of treatments or
      interventions to control cancer pain.
AB  - Pain is common in cancer patients. To ensure optimal pain management efficacy and
      effectiveness of new drugs and treatments have to be investigated in clinical
      trials. Efficacy trials such as randomised controlled trials (RCT) are
      experimental studies and estimate the maximum potential benefit to be derived
      from an intervention in ideal circumstances and under a controlled environment.
      RCTs are the only trial design to establish causal effects. A crossover study is
      a special type of RCT where patients serve as own controls. In efficacy studies
      the intervention and the control group should be as homogeneous as possible,
      confounding variables are controlled, bias is reduced, internal validity is high
      whereas external validity is low. Studies looking at effectiveness assess
      clinical practice and reflect real life circumstances. They rely high on external
      validity at the expense of careful controls, the study population is
      heterogeneous, confounding variables are examined. Cohort studies follow a group
      or groups of individuals with a common characteristic over a period of time to
      measure outcomes. Case-control studies start with the outcome and compare the
      characteristics of two groups of interest, those with the outcome and those
      without to identify factors which occur more or less often in the poor outcome
      group. Definition of outcome criteria is crucial both for efficacy and
      effectiveness studies and is often a primary problem. All clinical studies must
      use valid and reliable outcome measures.

PMID- 15265353
TI  - Increased family reports of pain or distress in dying Oregonians: 1996 to 2002.
AB  - The aim of this study was to compare the prevalence of family-reported pain or
      distress during the last week of decedents' lives during two times: November 1996
      to December 1997 and June 2000 to March 2002. We telephone-surveyed family
      caregivers of Oregonians who had died 2 to 5 months previously in private homes,
      nursing homes, and other community-based settings. Caregivers were asked to rate
      the level of pain or distress during the decedent's final week of life on a four
      point scale. Data were collected from 340 respondents from 1996-1997 and 1384
      respondents from 2000-2002. We found that the prevalence of family-reported
      moderate or severe pain or distress (compared to comfortable or mild pain or
      distress) in Oregon decedents increased from 30.8% in 1996-1997 to 48% in 2000
      2002. Using a logistic regression model to control for differences between the
      two sampling times and other predictors of increased pain or distress, decedents
      in 2000-2002 remained approximately twice as likely to be reported to be in
      moderate or severe pain or distress during the last week of their lives (Time 2
      vs. Time 1, odds ratio [OR] 2.09, 95% confidence interval [CI] 1.59-2.74). We
      discuss possible explanations for this finding, including media effect created by
      the publicity surrounding the second ballot measure and subsequent availability
      of physician-assisted suicide in November 1997. Alternatively, trends in under
      funding and under staffing of hospice and community nursing resources may have
      disproportionately affected care in the final week of life, which depends heavily
      on skilled nursing care for effective symptom control and psychosocial support of
      the patient and family.

PMID- 15265354
TI  - Acceptability of severe pain among hospitalized adults.
AB  - BACKGROUND: It is unclear why some hospitalized adults experiencing severe pain
      report that this degree of pain is acceptable to them. METHODS: A 25% random
      sample of cognitively intact patients admitted to nine medical/surgical units in
      a New York City hospital were enrolled. Patients were interviewed daily, Monday
      to Friday from April 1, 2001 through February 14, 2003, to collect information on
      the presence of pain, pain intensity, analgesic use, and acceptance of pain.
      Patients were asked to rate their current level of pain using a four-point scale.
      RESULTS: Three hundred ninety-two of 1254 patients ( 31%) experiencing severe
      pain reported that their pain was acceptable to them. Variables significantly
      associated with an episode of acceptable severe pain in multivariate analyses
      included resolution of the painful episode (odds ratio = 4.7; 95% confidence
      interval [CI], 3.54-6.17), recent surgery (odds ratio = 1.5; 95% CI, 1.11-1.99),
      African American compared to white (odds ratio = 0.7; 95% CI, 0.48-0.955), age
      (odds ratio = 0.985; 95% CI, 0.977-0.993), and patients taking analgesics (odds
      ratio = 0.7; 95% CI, 0.46-0.964 for nonsteroidal anti-inflammatory drugs
      [NSAIDs]/acetaminophen and odds ratio = 0.6; 95% CI, 0.46-0.85 for opioids).
      Overall, 86 of 252 (34%) reported the pain was acceptable because it had
      resolved, 47 (19%) believed the pain would eventually go away, and 47 (19%)
      reported they were able to tolerate the pain. CONCLUSIONS: A substantial
      percentage of patients reporting severe pain report this experience as
      acceptable. Given recent research linking high intensity pain to adverse
      outcomes, future studies directed at improving the management of pain need to
      target both pain intensity and patients' beliefs about the acceptability of
      severe pain.

PMID- 15265355
TI  - Oregon physicians' responses to requests for assisted suicide: a qualitative
      study.
AB  - In 1997, the Oregon Death with Dignity Act was enacted, allowing physicians to
      prescribe lethal dosages of medication to competent, terminally ill patients who
      request them. To improve our understanding of physicians' reactions to requests
      for assisted suicide, we performed semistructured interviews of 35 Oregon
      physicians who had received requests from patients. Interviews were completed in
      2000, and audiotaped, transcribed, and analyzed using qualitative techniques.
      Requests for assisted suicide had a powerful impact on physicians and their
      practices. Physicians often felt unprepared, and experienced apprehension and
      discomfort before and after receiving requests. Prominent sources of discomfort
      included concerns about adequately managing symptoms and suffering, not wanting
      to abandon patients, and incomplete understanding of patients' preferences,
      especially when physicians did not know patients well. Participation in assisted
      suicide required a large investment of time and was emotionally intense.
      Regardless of whether they prescribed or not, physicians did not express major
      regrets about their decisions. Requests often facilitated discussion of important
      issues, and many physicians felt that the process increased their confidence and
      assertiveness in discussing end-of-life issues with other patients. Physicians
      rarely sought support from colleagues; instead, they tended to discuss emotional
      aspects of their experiences with their spouses.

PMID- 15265356
TI  - Opioid dose titration for severe cancer pain: a systematic evidence-based review.
AB  - Dosing strategies to achieve rapid analgesia in patients with severe or crescendo
      cancer pain are important. A systematic review of research trials for treatment
      of severe or crescendo cancer pain was conducted; nine studies were identified.
      Eight trials were prospective; two were randomized between different dosing
      strategies. Dosing frequency predicted onset to analgesia regardless of baseline
      opioid dose. None of the trials were associated with evidence of respiratory
      depression. The studies all suffered significant methodological problems limiting
      broad conclusions. Until better data exist, opioid dose titration for
      severe/crescendo pain will be guided by expert opinion and experience.

PMID- 15265357
TI  - Opening the black box: physicians' inner responses to patients' requests for
      physician-assisted death.

PMID- 15265358
TI  - Broaching the topic of a palliative care consultation with patients and families
      #42.

PMID- 15265359
TI  - Responding to patient emotion #29.

PMID- 15265360
TI  - Cell shed.

PMID- 15265361
TI  - Communication across cultures.

PMID- 15265364
TI  - The Balm of Gilead Project: a demonstration project on end-of-life care for
      safety-net populations.
AB  - The Balm of Gilead is a comprehensive program of end-of-life care for the
      populations served by the "safety net" public health system in Alabama's largest
      county. The Balm of Gilead serves terminally ill persons, predominantly of
      minority ethnic status who as a group are relatively younger than the national
      hospice population, and typically lacking in personal financial resources. Care
      provided by the Balm of Gilead addresses the holistic needs associated with
      terminal illness in each of its stages and each of its treatment settings. Balm
      of Gilead professionals and volunteers provide continuity of care across a
      continuum that includes inpatient palliative care, home hospice services, and
      specialized palliative care in nursing homes and other community residential
      settings. Cooper Green Hospital and the Jefferson County Department of Health are
      principal partners in the program. Community partnerships with local foundations,
      colleges and universities, faith communities, civic groups, and professional
      groups complete the collaborative network of the Balm of Gilead Project. This
      report discusses work to date toward fulfilling the project's two primary
      objectives: (1) to build the infrastructure necessary to support a comprehensive
      palliative care program that is available to county residents regardless of their
      ability to pay and (2) to develop systems and services to foster the
      institutional and community values that promote excellence in end-of-life care.
      The Project's current status and future challenges are reviewed.

PMID- 15265365
TI  - Transformation of myelodysplastic syndromes into acute myeloid leukemias.
AB  - BACKGROUND: Myelodysplastic syndromes (MDSs), also called preleukemias, are a
      group of myeloid hematopoietic malignant disorders. We studied the transformation
      of MDS into acute myeloid leukemia (AML). METHODS: Leukemic transformation in 151
      patients with MDS was dynamically followed up. The clinical manifestation,
      peripheral blood and bone marrow condition, karyotypes, immunophenotypes,
      response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were
      also observed. RESULTS: During the course of this study, over the past eight
      years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt
      leukemia, with a median interval of 5 (1 - 23) months. There were no significant
      differences between rates of leukemic transformation in comparison with the
      refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in
      transformation (RAEB-t) patient groups. Transformation occurred either gradually
      or rapidly. There were five parameters positively correlated to leukemic
      transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15%
      blasts in the bone marrow, at least two abnormal karyotypes, and treatment with
      combined chemotherapy. All of the 21 patients with leukemia suffered from MDS
      AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed
      extramedullary infiltration. Leukopenia was found in 47.62% of these patients.
      Two thirds of these patients, whose bone marrows were generally hypercellular,
      suffered from neutropenia. After developing AML, 8 (47.06%) patients developed
      abnormal karyotypes. High expression of immature myeloid antigens, including CD33
      [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50
      +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone
      marrow mononuclear cells from MDS-AML patients after leukemic transformation. In
      some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with
      myeloid antigens. A low complete remission rate (31.25%) and a short survival
      time, with median survival of 6 (1 - 28) months, were found in patients with MDS
      AML treated by induction chemotherapy. CONCLUSIONS: MDS has a high risk of
      developing into AML, either gradually or rapidly. Patients with MDS-AML have
      specific biological characteristics and a worse prognosis.

PMID- 15265366
TI  - Expression patterns of WT-1 and Bcr-Abl measured by TaqMan quantitative real-time
      RT-PCR during follow-up of leukemia patients with the Ph chromosome.
AB  - BACKGROUND: This study was designed to quantitatively measure WT-1 expression
      levels in patients with chronic myelogenous leukemia (CML) and acute
      lymphoblastic leukemia (ALL) during follow-up and to clarify the value of WT-1 as
      a molecular marker in minimal residual disease monitoring. METHODS: The TaqMan
      quantitative real-time RT-PCR method was established by using cloned WT-1 cDNA or
      synthesized oligonucleotides resembling WT-1 cDNA fragments in limit dilution as
      template until a stable and reliable standard curve was obtained. In a 25-month
      follow-up, the transcriptional levels of WT-1, Bcr-Abl, and Abl gene, were
      quantitatively measured in bone marrow cells from 25 CML or acute lymphoblastic
      leukemia (ALL) patients with the Ph chromosome. In addition, the expression of
      these genes in 40 samples of normal peripheral blood was also examined using the
      same method. The ratios of WT-1/Abl and Bcr-Abl/Abl were both plotted, and the
      two expression patterns were compared as well as their clinical significance.
      RESULTS: The levels of WT-1 expression in normal peripheral blood were
      detectable. In CML and Ph positive ALL patients, WT-1 expression levels changed
      in parallel with the Bcr-Abl expression pattern as the disease progressed or
      responded to effective treatment. CONCLUSION: WT-1 expression provides a novel
      molecular marker in addition to Bcr-Abl for monitoring minimal residual disease
      (MRD) and targeting therapy in Ph chromosome-positive leukemia patients.

PMID- 15265367
TI  - Inhibition of NF-kappaB by mutant IkappaBalpha enhances TNF-alpha-induced
      apoptosis in HL-60 cells by controlling bcl-xL expression.
AB  - BACKGROUND: The aim of this study was to explore whether the inhibition of
      nuclear factor-kappaB (NF-kappaB) activation by mutant IkappaBalpha (S32, 36-->A)
      can enhance TNF-alpha-induced apoptosis of leukemia cells and to investigate the
      possible mechanism. METHODS: The mutant IkappaBalpha gene was transfected into HL
      60 cells by liposome-mediated techniques. G418 resistant clones stably expressing
      mutant IkappaBalpha were obtained by the limiting dilution method. TNF-alpha
      induced NF-kappaB activation was measured by electrophoretic mobility shift assay
      (EMSA). The expression of bcl-xL was detected by RT-PCR and Western blot after 4
      hours exposure of parental HL-60 and transfected HL-60 cells to a variety of
      concentrations of TNF-alpha. The percentage of apoptotic leukemia cells was
      evaluated by flow cytometry (FCM). RESULTS: Mutant IkappaBalpha protein was
      confirmed to exist by Western blot. The results of EMSA showed that NF-kappaB
      activation by TNF-alpha in HL-60 cells was induced in a dose-dependent manner,
      but was almost completely inhibited by mutant IkappaBalpha repressor in
      transfected cells. The levels of bcl-xL mRNA and protein in HL-60 cells increased
      after exposure to TNF-alpha, but changed very little in transfected HL-60 cells.
      The inhibition of NF-kappaB activation by mutant IkappaBalpha enhanced TNF-alpha
      induced apoptosis. The cytotoxic effects of TNF-alpha were amplified in a time-
      and dose-dependent manner. CONCLUSIONS: NF-kappaB activation plays an important
      role in the resistance to TNF-alpha-induced apoptosis. The inhibition of NF
      kappaB by mutant IkappaBalpha could provide a new approach that may enhance the
      anti-leukemia effects of TNF-alpha or even of other cytotoxic agents.

PMID- 15265368
TI  - Upregulation and activation of caspase-3 or caspase-8 and elevation of
      intracellular free calcium mediated apoptosis of indomethacin-induced K562 cells.
AB  - BACKGROUND: A nonsteroidal anti-inflammatory drug, indomethacin, has been shown
      to have anti-leukemic activity and induce leukemic cell apoptosis. This study was
      to elucidate the mechanism of indomethacin-induced K562 cell apoptosis. METHODS:
      K562 cells were grown in RPMI 1640 medium and treated with different doses of
      indomethacin (0 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L, 800
      micromol/L) for 72 hours. The cells were harvested, and cell viability or
      apoptosis was analyzed using MTT assay and AO/EB stain, combining laser scanning
      confocal microscopy (LSCM) technique separately. For the localization and
      distribution of intracellular caspase-3 or caspase-8 protein, immunofluorescence
      assay was carried out. To reveal the activation of caspase-3 or caspase-8 in
      indomethacin-treated cells, Western blot detection was used. The change in
      intracellular free calcium was determined by Fluo-3/Am probe labeling combined
      with LSCM. RESULTS: Indomethacin could lead to K562 cell apoptosis and inhibit
      cell viability in a concentration-dependent manner. An increased expression of
      intracellular caspase-3 or caspase-8 was observed at higher doses of indomethacin
      (400 - 800 micromol/L). Western blot results showed upregulation and activation
      in both caspase-3 and caspase-8 protein. Under indomethacin intervention, the
      levels of intracellular free calcium showed a significant increase. Blocking the
      activity of cyclooxygenase did not abolish the effects of indomethacin on K562
      cell apoptosis. CONCLUSIONS: Activation and upregulation of caspase-3 or caspase
      8 protein were responsible for Indomethacin-induced K562 cell apoptosis.
      Variation of intracellular free calcium might switch on the apoptotic pathway and
      the proapoptotic effect of indomethacin might be cyclooxygenase-independent.

PMID- 15265369
TI  - Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes.
AB  - BACKGROUND: Recent studies have indicated that many mutations in mitochondrial
      (mt) DNA NDI gene region are related to diabetes mellitus. In this study we
      explored the relationship between various mtDNA ND1 gene mutations and type 2
      diabetes mellitus (DM) among Chinese. METHODS: Using PCR restriction fragment
      length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA
      (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non
      diabetic subjects. RESULTS: In diabetic group, there were 13 carriers (2.72%) of
      3316 G-->A mutation,12 (2.51%) of 3394 T-->C mutation and 2 (0.42%) of 3426A-->G
      mutation. In controls, only 3394 T-->C mutation was observed in 2 subjects
      (0.47%). There was significant difference in the frequency of 3316 and 3394
      mutation between two groups (P < 0.05, respectively). More subjects with
      mitochondrial DNA ND1 gene mutations had DM family history and greater tendency
      of maternal inheritance when compared to those patients without mutation in
      diabetic group (P < 0.01). A 3426 mutation diabetic pedigree was studied, and we
      found 12 maternal members in the family had the same mutation. CONCLUSION: mtDNA
      ND1 gene mutations at nt3316 (G-->A), nt3394 (T-->C) and 3426 (A-->G) might
      contribute to the pathogenesis of DM with other genetic factors and environment
      factors.

PMID- 15265370
TI  - Role of connective growth factor in plasminogen activator inhibitor-1 and
      fibronectin expression induced by transforming growth factor beta1 in renal
      tubular cells.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) contributes greatly to renal
      tubulointerstitial fibrosis, which is the final event leading to end-stage renal
      failure. This study was designed to investigate the effects of CTGF antisense
      oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator
      inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by
      transforming growth factor beta1 (TGF-beta1) in addition to the role of CTGF in
      the accumulation and degradation of renal extracellular matrix (ECM). METHODS: A
      human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic
      lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC
      cells were stimulated with TGF-beta1 (5 microg/L), the mRNA levels of PAI-1 and
      fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was
      assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were
      determined by Western blot and ELISA, respectively. RESULTS: TGF-beta1 was found
      to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and
      fibronectin mRNA expression induced by TGF-beta1 was significantly inhibited by
      CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1
      protein synthesis and lowered the levels of PAI-1 and fibronectin protein
      secreted into the medium. CONCLUSIONS: CTGF may play a crucial role in the
      accumulation and degradation of excessive ECM during tubulointerstitial fibrosis,
      and transfecting CTGF antisense ODNs may be an effective way to prevent renal
      fibrosis.

PMID- 15265371
TI  - Activation of nuclear factor kappaB and induction of inducible nitric oxide
      synthase by lipid-associated membrane proteins isolated from Mycoplasma
      penetrans.
AB  - BACKGROUND: This study was designed to investigate the potential pathogenicity of
      Mycoplasma penetrans (M. penetrans) and its molecular mechanisms responsible for
      the induction of iNOS gene expression in mouse macrophages stimulated by lipid
      associated membrane proteins (LAMPs) prepared from M. penetrans. METHODS: Mouse
      macrophages were stimulated with M. penetrans LAMPs to assay the production of
      nitric oxide (NO). The expression of inducible nitric oxide synthase (iNOS) was
      detected by RT-PCR and Western blotting. The activity of nuclear factor kappaB
      (NF-kappaB) and the effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor
      of NF-kappaB, on the production of nitric oxide and the expression of iNOS were
      also assessed in mouse macrophages treated with M. penetrans LAMPs by indirect
      immunofluorescence and Western blotting. RESULTS: M. penetrans LAMPs stimulated
      mouse macrophages to produce nitric oxide in a dose- and time-dependent manner.
      The mRNA and protein levels of iNOS were also upregulated in response to LAMP
      stimulation and inhibited by PDTC treatment. M. penetrans LAMPs were found to
      trigger NF-kappaB activation, a possible mechanism for the induction of iNOS
      expression. CONCLUSION: This study demonstrated that M. penetrans may be an
      important etiological factor of certain diseases due to the ability of M.
      penetrans LAMPs to stimulate the expression of iNOS, which is probably mediated
      through the activation of NF-kappaB.

PMID- 15265372
TI  - Clinical features of hereditary spastic paraplegia with thin corpus callosum:
      report of 5 Chinese cases.
AB  - BACKGROUND: Hereditary spastic paraplegia is a clinically and genetically
      heterogeneous group of neurodegenerative disorders of the motor system,
      characterized by slowly progressive spasticity and weakness of the lower
      extremities. This study was conducted to investigate the clinical features of
      hereditary spastic paraplegia with thin corpus callosum (HSP-TCC). METHODS:
      Clinical data from five patients and thirty-five previously published case
      reports of HSP-TCC were analyzed retrospectively. RESULTS: Most patients were
      adolescents at the onset of the disease, presenting with spastic paraparesis of
      the lower limbs and mental impairment. Some patients also had other clinical
      features, including spasticity of the upper limbs, cerebellar ataxia, and sensory
      disturbances. Cranial MRIs of the five patients revealed an extremely thin corpus
      callosum, sometimes with widened cerebral sulci and ventricles, as well as with
      cerebellar and cerebral atrophy. CONCLUSION: The main clinical features of HSP
      TCC include slowly progressive spastic paraplegia, mental impairment during the
      second decade of life, and an extremely thin corpus callosum as shown on cranial
      MRIs.

PMID- 15265373
TI  - Efficacy of non-penetrating trabecular surgery for open angle glaucoma: a meta
      analysis.
AB  - BACKGROUND: Non-penetrating trabecular surgery is a new filtrating surgery
      without opening in ternal trabecular structures. This study was to estimate the
      overall efficacy of non-penetrating trabecular surgery for open angle glaucoma.
      METHODS: The published articles selected for this study were obtained by a
      computerised Medline and China Biological Medicine Disk search of the literature
      and a manual search of the bibliographies of relevant articles. Articles meeting
      the inclusion criteria were reviewed systematically, and the reported data were
      aggregated using the statistical techniques of meta-analysis. RESULTS: A total of
      37 articles were included in the meta-analysis. The pooled complete success rates
      of non-penetrating trabecular surgery with different techniques were: deep
      sclerectomy single, 69.7% (95% CI: 58.5% - 81.0%); deep sclerectomy with collagen
      implant, 59.4% (95% CI: 47.0% - 71.8%); deep sclerectomy with reticulated
      hyaluronic acid implant, 71.1% (95% CI: 56.8% - 85.3%); and viscocanalostomy,
      72.0% (95% CI: 57.6% - 86.4%). The overall weighted complete success rate of non
      penetrating trabecular surgery was 67.8% (95% CI: 61.4% - 74.3%). CONCLUSIONS:
      Non-penetrating trabecular surgery is the best available therapy method for
      medically uncontrolled open angle glaucoma with a complete success rate of over
      60%. But the different techniques cannot belie the complete success rate of non
      penetrating trabecular surgery.

PMID- 15265374
TI  - Cortical language activation in aphasia: a functional MRI study.
AB  - BACKGROUND: Functional neuroimaging has been used in neurolinguistic research on
      normal subjects and on patients with brain damage. This study was designed to
      investigate the differences of the neural basis underlying language processing
      between normal subjects and aphasics. METHODS: Functional magnetic resonance
      imaging (fMRI) was used to map the language network in 6 normal subjects and 3
      patients with aphasia who were in the stage of recovery from acute stroke. The
      participants performed a word generation task during multi-slice functional
      scanning for the measurement of signal change associated with regional neural
      activity induced by the task. RESULTS: In normal subjects, a distributed language
      network was activated. Activations were present in the frontal, temporal,
      parietal and occipital regions. In the patient group, however, no activation was
      detected in the left inferior frontal gyrus whether the patient had a lesion in
      the left frontal lobe or not. Two patients showed activations in some right
      hemisphere regions where no activation appeared in normal subjects. CONCLUSIONS:
      fMRI with word generation task is feasible for evaluating language function in
      aphasic patients. Remote effect of focal lesion and functional redistribution or
      reorganisation can be found in aphasic patients.

PMID- 15265375
TI  - Activation of protein kinase A alters subnuclear distribution pattern of human
      steroidogenic factor 1 in living cells.
AB  - BACKGROUND: The aim of this study was to identify the subnuclear distribution
      pattern of human orphan nuclear receptor steroidogenic factor 1 (SF-1) in living
      cells with and without the activation of protein kinase A (PKA) signal pathway,
      and thus try to explain the unknown mechanism by which PKA potentiates SF-1
      transactivation. METHODS: Full-length cDNAs of wild type and a naturally
      occurring mutant (G35E) human SF-1 were cloned and fused with green fluorescent
      protein (GFP). Subcellular distribution pattern of human SF-1 in living cells,
      whose PKA signaling was either activated or not, was studied by laser confocal
      microscopy after the validity of the gene sequence was confirmed. RESULTS: The
      transactivation ability of the GFP-SF-1 chimeric protein was highly conserved.
      Wild type human SF-1 diffused homogeneously within the nuclei of cells when PKA
      was not active, and converged to clear foci when PKA was activated. Mutant SF-1
      diffused within the nuclei even in the presence of PKA activation, surprisingly
      aggregating as fluorescent dots inside the nucleoli, a phenomenon not altered by
      PKA. CONCLUSIONS: Activation of PKA causes wild type, but not mutant SF-1 to
      alter its subnuclear distribution pattern to a transactivationally active form
      (foci formation). This finding may throw new light on the mechanism by which PKA
      activates the orphan nuclear receptor.

PMID- 15265376
TI  - Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial
      growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary
      hypertension.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is one of the pivotal
      mediators in the response of lungs to decreased oxygen availability, and
      increasingly has been implicated in the pathogenesis of pulmonary hypertension.
      Vascular endothelial growth factor (VEGF), a downstream target gene of HIF
      1alpha, plays an important role in the pathogenesis of hypoxic pulmonary
      hypertension and hypoxic pulmonary artery remodelling. In this study, we
      investigated the dynamic expression of HIF-1alpha and VEGF in pulmonary artery of
      rats with hypoxia-induced pulmonary hypertension. METHODS: Forty male Wistar rats
      were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial
      pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI)
      were estimated. Lungs were inflated and fixed for in situ hybridisation and
      immunohistochemistry. RESULTS: mPAP values were significantly higher than the
      control values after 7days of hypoxia [(18.4 +/- 0.4) mmHg, P < 0.05]. RVHI
      developed significantly after 14 days of hypoxia. Expression of HIF-1alpha
      protein increased in pulmonary arterial tunica intima of all hypoxic rats. In
      pulmonary arterial tunica media, HIF-1alpha protein was markedly increased by day
      3 (0.20 +/- 0.02, P < 0.05), reached the peak by day 7, then declined after day
      14 of hypoxia. HIF-1alpha mRNA increased significantly after day 14 of hypoxia
      (0.20 +/- 0.02, P < 0.05). VEGF protein began to increase markedly after day 7 of
      hypoxia, reaching its peak around day 14 of hypoxia (0.15 +/- 0.02, P < 0.05).
      VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less
      stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and
      tunica media, whereas VEGF protein is located predominantly in tunica intima.
      Linear analysis showed that HIF-1alpha mRNA, VEGF and mPAP were correlated with
      hypoxic pulmonary artery remodelling. HIF-1alpha mRNA was positively correlated
      with VEGF mRNA and protein (P < 0.01). CONCLUSION: HIF-1alpha and VEGF are both
      involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.

PMID- 15265377
TI  - Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and
      serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center,
      randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: Raloxifene has been approved for prevention and treatment of
      postmenopausal osteoporosis in Caucasian women. It also has some positive effects
      on serum lipids in Caucasians. The objective of this study was to determine the
      effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral
      density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women
      with osteoporosis. METHODS: This was a multi-center, randomized, double-blind,
      placebo-controlled clinical trial in which 204 postmenopausal Chinese women with
      osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment
      daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were
      measured before and after drug administration. BMD was measured by Dual-Energy X
      Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step
      enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic
      analysis. RESULTS: At the end of the 12-month study, lumbar spine BMD increased
      in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and
      (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in
      total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of
      (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene
      group had a new vertebral fracture and 5 placebo subjects had new fractures (P >
      0.05). In the raloxifene group, the median decreases in the biochemical markers
      of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%,
      respectively. These changes were statistically significant compared with those in
      the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total
      cholesterol and low-density lipoprotein cholesterol decreased significantly in
      the raloxifene group compared with those in the placebo group (P < 0.001,
      respectively) and there was no significant effect of raloxifene on high-density
      lipoprotein cholesterol and triglycerides compared with placebo. CONCLUSIONS:
      Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total
      hip BMD, significantly decreases bone turnover, and has favourable effects on
      serum lipids in Chinese postmenopausal women with osteoporosis.

PMID- 15265378
TI  - Effects of low-dose radiation on tumor growth, erythrocyte immune function and
      SOD activity in tumor-bearing mice.
AB  - BACKGROUND: Activating on mammalian and human body LDR is thought to induce
      adaptive response, enhance immune function and increase anti-tumor ability. This
      study was designed to assess the effect of low-dose radiation on tumor growth and
      on erythrocyte immune function and superoxide dismutase (SOD) activity in tumor
      bearing mice. METHODS: Male Kunming mice were subcutaneously implanted with S180
      sarcoma cells in the right inguen to create an experimental in situ animal model.
      Six hours before implantation, the mice were given 75 mGy X-ray radiation, over
      the body. Tumor size was observed 5 days later while tumor volume was calculated
      every other day, allowing for the creation of a graph depicting tumor growth.
      Fifteen days after implantation, the mice were killed to measure tumor weight and
      observe the necrotic areas and the location of tumor-infiltrating lymphocytes
      (TILs). Erythrocyte immune function and SOD activity were also determined.
      RESULTS: Mice pre-exposed to low-dose radiation had a lower tumor formation rate
      than did those receiving no radiation (P < 0.05). Tumor growth was significantly
      lower in the mice pre-exposed to low-dose radiation; after 15 days, the average
      tumor weight in the mice pre-exposed to low-dose radiation was also lower (P <
      0.05). Areas of tumor necrosis and infiltration of TILs were larger in the low
      dose radiation group than in the non-radiation group. Erythrocyte immune function
      and SOD activity were higher in the low-dose radiation group than in the non
      radiation group (P < 0.05). CONCLUSION: Low-dose radiation can markedly increase
      the anti-tumor ability of an organism and improve erythrocyte immune function and
      red blood cell SOD activity as well, suggesting that low-dose radiation might be
      useful in the clinical treatment of cancer.

PMID- 15265379
TI  - Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in
      kidneys of diabetic rats.
AB  - BACKGROUND: The changes in matrix metalloproteinase-2 (MMP-2) and matrix
      metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic
      rats to investigate the degradative pathway of collagen type IV (C-IV) and the
      protective effects of pioglitazone on an experimental model of diabetic
      nephropathy. METHODS: In 54 SD rats used in our study, 18 served as normal
      controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by
      intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats
      were allocated at random to receive pioglitazone [20 mg.kg(-1).d(-1)] in their
      drinking water and 18 served as diabetic controls. Rats were killed after 2, 4,
      or 8 weeks of treatment. Kidneys were examined pathomorphologically and the
      expressions of MMP-2, MMP-9, and C-IV were analyzed by immunohistochemistry, and
      the results were quantified by image analysis techniques. RESULTS: Diabetes
      mellitus was associated with a decrease in the expression of MMP-2 in the
      glomeruli (P < 0.05, vs control). By contrast, MMP-2 expression in the
      interstitium increased, but not significantly (P > 0.05, vs control). The
      expression of MMP-9 did not show any change when comparing the three groups (P >
      0.05, vs control). STZ-diabetic rats were also associated with an increase in the
      expression of C-IV in the glomeruli and the interstitium (P < 0.05, vs control).
      All diabetes-associated changes in MMP-2 expression were attenuated by
      pioglitazone treatment in association with reduced C-IV accumulation.
      CONCLUSIONS: These results indicate that a decrease in MMP-2 expression in the
      glomeruli of diabetic rats may lead to impairment of C-IV degradation and
      contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone
      treatment, which can attenuate the decrease of glomerular MMP-2 and the increase
      of C-IV degradation, has curative effects on diabetic nephropathy.

PMID- 15265380
TI  - Capsule endoscopy and push enteroscopy in the diagnosis of obscure
      gastrointestinal bleeding.
AB  - BACKGROUND: In obscure gastrointestinal (GI) bleeding, it is often difficult to
      detect the bleeding sites located in the small bowel with conventional
      radiological, scintigraphic or angiographic techniques. Push enteroscopy and
      capsule endoscopy are currently considered to be the most effective diagnostic
      procedures. The aim of this study was to compare the detection rates between
      capsule endoscopy and push enteroscopy. METHODS: From May 2002 through January
      2003, we prospectively examined by capsule endoscopy 39 patients with suspected
      small bowel diseases, in particular GI bleeding of unknown origin in Renji
      Hospital. Among them, 32 complained of obscure recurrent GI bleeding. Between
      January 1993 and October 1996, we used push enteroscopy on 36 patients who
      suffered from unexplained GI bleeding. All patients had prior normal results on
      gastroscopy, colonoscopy, small bowel barium radiography, scintigraphy and/or
      angiography. RESULTS: M2A capsule endoscopy disclosed abnormal small bowel
      findings in 26 (82%) out of 32 patients. Twenty-one of them had significant
      pathological findings explaining their clinical disorders. Diagnostic yield was
      therefore 66% (21 of 32 patients). Definite bleeding sites diagnosed by capsule
      endoscopy in 21 patients included angiodysplasia (8), inflammatory small-bowel
      (5), small-bowel polyps (4), gastrointestinal stromal tumour (2), carcinoid
      tumour and lipoma (1), and hemorrhagic gastritis (1). Push enteroscopy detected
      the definite sources of bleeding in 9 (25%) of the 36 patients. Patients with
      definite bleeding sources included angiodysplasias (2), leiomyosarcoma (2),
      leiomyoma (1), lymphoma (1), Crohn's disease (1), small-bowel polyps (1) and
      adenocarcinoma of ampulla (1). Suspected bleeding sources were shown by push
      enteroscopy in two additional patients (6%), and in other five patients (16%) by
      capsule endoscopy. CONCLUSIONS: The present study of patients with obscure GI
      bleeding showed that capsule endoscopy significantly superior to push enteroscopy
      in detecting GI bleeding (P < 0.001). Capsule endoscopy is safe and painless, and
      should become the initial diagnostic choice for patients with obscure GI
      bleeding.

PMID- 15265381
TI  - Cryopreservation of human embryonic stem cells by vitrification.
AB  - BACKGROUND: The efficiency of traditional cryopreservation of human embryonic
      stem (ES) cells is low, and there have been few attempts to prove new
      cryopreservation methods effective. This study was designed to evaluate the
      efficiency of cryopreservation of human ES cells using vitrification method.
      METHODS: Human ES cells clumped from an identical cell line were randomly
      allocated to be cryopreserved by vitrification or by slow freezing. The recovery
      rates, the growth and differentiation potential of thawed human ES cells were
      compared between these two groups. The pluripotency of human ES cells after
      thawing was identified. RESULTS: Eighty-one point nine percent (59/72) of human
      ES cell clumps were recovered after vitrification, while only 22.8% (16/70) were
      recovered after slow freezing (P < 0.01). The colonies after vitrification
      manifested have not only faster growth but also a lower level of differentiation
      when compared to colonies subjected to the slow freezing protocol. However, the
      rates of growth and differentiation in undifferentiated colonies from both groups
      were identical to the rates in those of non-cryopreserved stem cells after a
      prolonged culture period. Passage 6 of vitrified human ES cells retained the
      properties of pluripotent cells, a normal karyotype and expressed the
      transcription factor OCT-4, stage specific expressed antigen-4 (SSEA-4) and SSEA
      3. Teratoma growth of these cells demonstrated the ability to develop into all
      three germ layers. CONCLUSIONS: Vitrification is effective in cryopreserving
      human ES cells. During a prolonged culture, human ES cells retain their
      pluripotency after cryopreservation.

PMID- 15265382
TI  - Single photon emission computer tomography of dopamine transporters in monkeys
      and humans with 99mTc-TRODAT-1.
AB  - BACKGROUND: The diagnosis of Parkinson's disease is presently based on non
      specific symptoms. However, radionuclide dopamine transporters imaging can
      provide specific diagnostic tool for Parkinson's disease. This study was designed
      to investigate the effects of imaging of dopamine transporters with 99mTc-TRODAT
      1 in early diagnosis or differential diagnosis of Parkinson's disease. METHODS:
      Nine normal monkeys were used to establish N-methyl-4-phenyl-1, 2, 3, 6-tetra
      hydropyridine (MPTP) hemi-Parkinsonian animal models, and they were subjected to
      imaging. Twenty-nine patients with Parkinson's disease, 12 age-matched healthy
      volunteers, and 18 age-matched patients with Parkinson's syndrome were
      investigated. Single photon emission computer tomography (SPECT) was performed 3
      hours after intravenous injection of 740 MBq 99mTc-TRODAT-1. Striatum specific
      uptake of 99mTc-TRODAT-1 was calculated according to the ratio of striatum (ST)
      to cerebellum (CB) in dopamine transporters uptake. RESULTS: In normal monkeys,
      bilateral ratio of ST/CB was 2.34 +/- 0.41. After the injection of MPTP, uptake
      rate of 99mTc-TRODAT-1 at damaged region was much lower than that at the
      contralateral region, resulting in a significant difference in the ratio of ST/CB
      (right: ST/CB = 1.73 +/- 0.35; left: ST/CB = 1.90 +/- 0.30), especially in hemi
      Parkinsonian model monkeys (right: ST/CB = 1.29 +/- 0.17; left: ST/CB = 1.80 +/-
      0.33). The ratios of ST/CB were 1.57 +/- 0.17 and 1.61 +/- 0.14 for the right and
      left respectively in the healthy volunteers, 1.04 +/- 0.29 and 1.06 +/- 0.30 in
      the age-matched patients with Parkinson's disease, and 1.56 +/- 0.17 and 1.59 +/-
      0.18 in the age-matched patients with Parkinson's disease syndrome. A significant
      difference was noted between group of Parkinson's disease, normal controls and
      Parkinson's disease syndrome. CONCLUSION: The results suggest that 99mTc-TRODAT-1
      dopamine transporters SPECT has clinical application value in early diagnosis or
      differential diagnosis of Parkinson's disease.

PMID- 15265384
TI  - Characterization of DNA antigens from immune complexes deposited in the skin of
      patients with systemic lupus erythematosus.
AB  - BACKGROUND: Skin lesions are common manifestations in systemic lupus
      erythematosus (SLE). It is still unknown what the definite pathogenesis of skin
      involvement was and whether DNA participated in it. Our study was designed to
      explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in
      the skin lesions of patients with SLE. METHODS: Thirty skin samples from patients
      with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated
      by indirect immunofluorescence methods. The deposited immune complexes were
      extracted by cryoprecipitation, and DNA was then isolated with phenol and
      chloroform. DNA fragment sizes were detected by agarose gel electrophoresis.
      Finally, 8 different probes were used to analyze the origin of these DNA
      molecules using Dot hybridization. RESULTS: Extracellular DNA staining was found
      only in skin lesions, mainly those located in the basement membrane zone,
      vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed
      no fluorescence at locations outside the nuclei. There were no differences in the
      rate and intensity of extracellular DNA staining when comparing active phase to
      remission phase patients. No relationship was found between extracellular DNA and
      circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four
      bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp.
      Small sized fragments (100-200 bp) were positively correlated with disease
      activity (P < 0.05, r = 0.407). Dot hybridization showed significant homology of
      the various extracellular DNA fragments examined with human genomic DNA, but not
      with DNA from the microorganisms and viruses we examined. There were also
      homologies between DNA samples from different individuals. CONCLUSIONS: DNA and
      its immune complexes may contribute to the pathogenesis of skin lesions in SLE.
      These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in
      origin.

PMID- 15265383
TI  - Significance of changes in transforming growth factor-beta mRNA levels in
      autogenous vein grafts.
AB  - BACKGROUND: This study was designed to investigate changes in mRNA levels of
      transforming growth factor-beta (TGF-beta), collagen I, and collagen III in
      autogenous vein grafts. METHODS: Twenty-four New Zealand rabbits were randomly
      divided into 4 groups with 6 rabbits each. The external jugular veins of the New
      Zealand rabbits were harvested and grafted into the ipsilateral carotid artery.
      All rabbits were fed with a standard diet. After the operation, the rabbits were
      sacrificed at 1, 2, 3, or 4 weeks. TGF-beta, collagen I, and collagen III mRNA
      levels in the venous grafts were measured by semiquantitative methods at every
      time point. The contralateral external jugular veins were also harvested and
      analyzed as controls. Glyceraldehyde-3-phosphate dehydrogenase was used as an
      internal standard to normalize all samples for potential variations in mRNA
      content. In order to observe the expression of TGF-beta protein,
      immunohistochemical SABC methods were used. RESULTS: One week postoperation, the
      mRNA level of TGF-beta was upregulated to 1.73 +/- 0.19 in the vein graft and
      1.21 +/- 0.16 in the control vein (P < 0.01). High mRNA levels were maintained
      until week 4 postoperation. The mRNA levels of collagen I and collagen III were
      also significantly increased to 2.18 +/- 0.21 versus 1.12 +/- 0.24 and 1.08 +/-
      0.13 versus 0.83 +/- 0.12, respectively (P < 0.05). Immunohistochemical staining
      revealed a higher density of TGF-beta expression in the vein grafts. CONCLUSIONS:
      An uninterrupted increase in mRNA levels of TGF-beta, collagen I, and collagen
      III is observed in autogenous vein grafts. This increase may be the major cause
      of intimal hyperplasia, sclerosis, and even graft failure.

PMID- 15265385
TI  - Brain hyaluronan binding protein inhibits tumor growth.
AB  - BACKGROUND: Great efforts have been made to search for the angiogenic inhibitors
      in avascular tissues. Several proteins isolated from cartilage have been proved
      to have anti-angiogenic or anti-tumour effects. Because cartilage contains a
      great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding
      proteins (HABP), therefore, we speculated that HABP might be one of the factors
      regulating vascularization in cartilage or anti-angiogenesis in tumours. The
      purpose of this research was to evaluate the effects of hyaluronan binding
      protein on inhibiting tumour growth both in vivo and vitro. METHODS: A unique
      protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned
      from human brain cDNA library. MDA-435 human breast cancer cell line was chosen
      as a transfectant. The in vitro underlying mechanisms were investigated by
      determining the possibilities of MDA-435/b-HABP colony formation on soft agar,
      the effects of the transfectant on the proliferation of endothelial cells and the
      expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study
      included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos
      and nude mice. RESULTS: Colony formation assay revealed that the colonies formed
      by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The
      conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells
      in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The
      size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than
      that of MDA-435 alone. CONCLUSIONS: Human brain hyaluronan binding protein (b
      HABP) may represent a new kind of naturally existing anti-tumour substance. This
      brain-derived glycoprotein may block tumour growth by inducing apoptosis of
      cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting
      proliferation of endothelial cells.

PMID- 15265386
TI  - Down-regulation of mitotic checkpoint in transformed human embryo lung
      fibroblasts induced by N-methyl-N'-nitro-N-nitrosoguaridine.
AB  - BACKGROUND: Mutations in mitotic checkpoint genes have been detected in several
      human cancers, which exhibit chromosome instability. We wanted to know whether
      mutation of hBub1 could occur in transformed human embryo lung fibroblasts (HELF)
      cells induced by a chemical carcinogen. METHODS: HELF cells were transformed by N
      methyl-N'-nitro-N-nitrosoguaridine (MNNG), and three flasks of transformed HELF
      cells (named as T1, T2, and T3) were selected as amplifiers, and mutations of
      hBub1 in these transformed cells were analyzed by PCR-SSCP and sequencing.
      RESULTS: It was found that any one of three transformed cell lines exhibited
      aneuploidy with a low mitotic checkpoint function. Subsequent PCR-SSCP and
      sequence analysis showed an AGT to CGT or ATT mutation at codon 80 in hBub1 gene
      in T1 cells with a resultant change in amino acid sequence. CONCLUSION: Our study
      demonstrated that the mitotic checkpoint genes could be targets of MNNG.

PMID- 15265387
TI  - RNA interference and its current application in mammals.
AB  - OBJECTIVE: The aim of this review was to assess RNA interference (RNAi) and its
      possibility as a potential and powerful tool to develop highly specific double
      stranded RNA (dsRNA) or small interfering RNA (siRNA) based gene-silencing
      therapeutics. DATA SOURCES: The data used in this review were obtained from the
      current RNAi-related research reports. STUDY SELECTION: dsRNA-mediated RNAi has
      recently emerged as a powerful reverse genetic tool to silence gene expression in
      multiple organisms. The discovery that synthetic duplexes of 21 nucleotides
      siRNAs trigger gene-specific silencing in mammalian cells has further expanded
      the utility of RNAi in to the mammalian system. DATA EXTRACTION: The currently
      published papers reporting the discovery and mechanism of RNAi phenomena and
      application of RNAi on gene function in mammalian cells were included. DATA
      SYNTHESIS: Since the recent development of RNAi technology in the mammalian
      system, investigators have used RNAi to elucidate gene function, and to develop
      gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector.
      The general and sequence-specific inhibitory effects of RNAi that will be
      selective, long-term, and systemic to modulate gene targets mentioned in similar
      reports have caused much concern about its effectiveness in mammals and its
      eventual use as a therapeutic mordality. CONCLUSIONS: It is certain that the
      ability of RNAi in mammals to silence specific genes, either when transfected
      directly as siRNAs or when generated from DNA vectors, will undoubtedly
      accelerate the study of gene function and might also be used as a potentially
      useful method to develop highly gene-specific therapeutic methods. It is also
      expected that RNAi might one day be used to treat human diseases.

PMID- 15265388
TI  - High risk genetic factor in Chinese patients with idiopathic male infertility:
      deletion of DAZ gene copy on Y chromosome.

PMID- 15265389
TI  - Prediction of thrombolytic therapy for acute venous thromboembolic disease by CT
      pulmonary angiography and indirect CT venography.

PMID- 15265390
TI  - Phage displaying epitope of Candida albicans HSP90 and serodiagnosis.

PMID- 15265391
TI  - Relationship between expression of CD40-CD40 ligand system and serum cholesterol
      levels in patients with hypercholesterolemia.

PMID- 15265392
TI  - Clinical features and minimally invasive surgery of insular lesions: report of 42
      cases.

PMID- 15265393
TI  - Non-invasive diagnostic screening of hepatic fibrosis in patients with chronic
      hepatitis B.

PMID- 15265394
TI  - Concomitant diabetic ketoacidosis and rhinocerebral mucormycosis: report of a
      case.

PMID- 15265395
TI  - Platypnea-orthodeoxia and blockpnea as two unrecognized or underdiagnosed causes
      of medically unexplained dyspnea.

PMID- 15265396
TI  - [The selection and application of appendix in situ in the continent urinary
      diversion].
AB  - OBJECTIVE: To evaluate the elective method and the clinical experience of using
      appendix in situ in continent urinary diversion. METHODS: 26 continent urinary
      diversions have been performed since 1990. Among them, 11 cases underwent the
      intussuscepted technique and other 15 cases underwent embedded technique.
      RESULTS: The continent rate was 100% at the daytime among all the case, while
      intermittent incontinence occurred in 3 cases at night, which happened in the
      intussuscepted group. Other complications included catheterization difficulty in
      3 cases, appendix perforation in 1 case, which happened in the embedded group,
      traction of the appendix into abdominal cavity in 1 case, and prolapse of the
      intussusepted appendix in 3 cases. CONCLUSIONS: The embedded technique shows
      better results than the intussuscepted technique in term of continence. The
      embedded technique, using appendix in situ as an efferent loop, shows the
      advantages of easily performing, timesaving, better outcome in continence and
      less complication. We believe the technique of appendix in situ as an efferent
      loop is an ideal modality in urinary diversion operation.

PMID- 15265397
TI  - [Submucosal injection of anti-tumor drug on the prevention of Post-TUR-Bt
      recurrence].
AB  - OBJECTIVE: To study a new and practical method to prevent the superficial bladder
      tumor recurrence after transurethral resection of bladder tumor (TUR-Bt).
      METHODS: We had chosen 68 patients with superficial bladder tumor randomly. After
      TUR-Bt, we inserted special stainless steel injection needle through the
      operation hole, and then injected anti-tumor drugs (pirarubicin) submucously; in
      the control group, 74 patients were given traditional perfusion therapy for
      carcinoma in bladder with the same anti-tumor drug (pirarubicin) after TUR-Bt.
      The effects were evaluated according to recurrence ratio. RESULTS: The recurrence
      rate of injection group was 11.8% (8/68), and that of the control group was 29.7%
      (22/74). There is a very significant difference between the two groups (chi(2) =
      0.013, P < 0.01). The overall median recurrence interval period of injection
      group was obviously longer than that of the control group, but there was no
      significant difference about single and multiple occurrences between the two
      groups (chi(2) = 0.719, P > 0.05). CONCLUSIONS: The injection method used to
      prevent tumor recurrence after TUR-Bt has the following virtues: simple and safe,
      less side effect, more economical. We demonstrated that submucosal injection is a
      practical method to prevent tumor recurrence and is worth popularizing.

PMID- 15265398
TI  - [The evaluation of the diagnosis and treatment of 32 cases with ectopic ACTH
      syndrome].
AB  - OBJECTIVE: To investigate and discuss the diagnosis and treatment of ectopic ACTH
      syndrome. METHODS: Clinical data of 32 cases of ectopic ACTH syndrome, recruited
      from January 1990 to April 2003 in our hospital, was analyzed. RESULTS: All of
      the 32 cases presented with clinical and biochemical evidences of Cushing's
      syndrome. Ten cases were definitively diagnosed as ectopic ACTH syndrome by
      finding ectopic tumors; 4 cases were highly suspected as ectopic ACTH by blood
      sampling from femoral vein and infra-petrosal vein and 18 cases were suspected as
      ectopic ACTH by imaging examinations. Fifteen cases (47%), without identified
      source of ectopic hormone, were treated with bilateral or unilateral total
      adrenalectomy, with 1-year survival rate of 60%. Seven cases (22%), with possible
      source of ectopic hormone, underwent no intervention, with 1-year survival rate
      of 0. Ten cases underwent radical resection of tumor, 6 of which were bronchial
      carcinoids and 4 of which were thymic carcinoids, with 1-year survival rate of
      60%. CONCLUSION: It is very difficult to localize the tumor of ectopic ACTH
      syndrome patients. Bilateral adrenalectomy followed by hormonal replacement is
      effective for most of the patients without identifying source of ectopic hormone.

PMID- 15265399
TI  - [The analysis of the factors for postoperative blood pressure recovery of
      aldosterone producing adenoma patients].
AB  - OBJECTIVE: To investigate the factors regarding the recovery of postoperative
      blood pressure of aldosterone producing adenoma (APA) patients. METHODS: Sixty
      eight patients with APA were recruited and their data including retinal blood
      vessel by Doppler sonography, urinary trace albumin, pathological changes of
      renal biopsy and the adrenal tissues around the adenoma were analyzed in order to
      determine the correlation between these data and postoperative durative
      hypertension. RESULTS: Postoperative durative hypertension occurred in 14 cases
      (41.2%) with increased resistance of unilateral or bilateral central artery of
      retina, in 16 cases (66.7%) with increased level of urinary trace albumin.
      Fifteen cases underwent renal biopsy and all of them showed different
      pathological alterations, 11 cases (73.3%) of which presented with postoperative
      durative hypertension. The pathological changes of the adrenal tissues around the
      adenoma is either atrophy or non-atrophy (normal or hyperplasia), 8 cases (40%)
      and 10 cases (22.2%) of which showed postoperative durative hypertension,
      respectively. CONCLUSION: The renal pathological changes and increased resistance
      of retinal blood vessel are the main reasons leading to postoperative
      hypertension in patients with APA.

PMID- 15265400
TI  - [Evaluation of absolute alcohol treatment for renal cyst with percutaneous
      puncture and catheterization under ultrasonographic guidance].
AB  - OBJECTIVE: To evaluate the effect of absolute alcohol treatment for renal cyst
      with percutaneous puncture and catheterization. METHODS: This report presented 64
      cases of renal cysts, 34 cases were treated with percutaneous puncture (A group)
      and 30 cases with percutaneous catheterization (B group). According to the size,
      the cysts were divided into 2 groups, more than 6 cm in diameter and less than 6
      cm in diameter. RESULTS: All the patients were followed up for 3 - 12 months by
      CT or B ultrasonography. Striking difference of the therapeutic results were
      existed when cystS were more than 6 cm in diameter. CONCLUSION: Percutaneous
      catheterization is applicable to the sclerosing treatment of renal cyst whose
      diameter is more than 6 cm.

PMID- 15265401
TI  - [Significance and limitations of f/tPSA in differential diagnosis of prostate
      cancer with tPSA levels between 4 and 10 ng/ml].
AB  - OBJECTIVE: To study significance and limitations of the ratio of free to total
      prostate specific antigen (f/t PSA) in differential diagnosis between prostate
      cancer and benign prostatehyperplasia (BPH) with total PSA (tPSA) levels between
      4 and 10 ng/ml. METHODS: We analysed retrospectively 180 prostate cancer and BPH
      patients who were diagnosed and treated in our hospital from October 1998 to
      October 2002 and had serum tPSA levels between 4 and 10 ng/ml. Of the 180
      patients, 36 (20%) were histologically confirmed as prostate cancer and 144 (80%)
      BPH. The tPSA and free PSA (fPSA) in serum were measured by micropartical enzyme
      immunoassay. Prostate volume was measured by transabdominal ultrasonography. We
      chose Student's t-test for comparison between prostate cancer and BPH groups. The
      correlation between prostate volume and f/t PSA was analyzed using Pearson's
      correlation coefficient. RESULTS: The mean values of tPSA and f/t PSA were 6.75
      ng/ml and 0.17 in patients with prostate cancer, 6.48 ng/ml and 0.25 in patients
      with BPH. The mean value of tPSA wasn't significantly different between patients
      with prostate cancer and BPH (P > 0.05). However, the mean value of f/t PSA of
      patients with prostate cancer was significantly lower than that of patients with
      BPH (P < 0.01). Furthermore, there were significant and positive correlation
      between prostate volume and f/t PSA in both groups with prostate cancer and BPH
      (prostate cancer group's correlation coefficient (r = 0.50, P < 0.01); BPH group
      (r = 0.24, P < 0.01). There was significant difference in f/t PSA between
      prostate cancer and BPH patients with prostate volumes more than 40 cm(3) (P <
      0.05), but not between these two groups with prostate volumes more than 40 cm(3)
      (P > 0.05). CONCLUSION: The f/t PSA is significant in differential diagnosis
      between prostate cancer and BPH with tPSA levels between 4 and 10 ng/ml. But
      prostate volume has an effect on f/tPSA. The f/tPSA has diagnostic value of
      differentiation only when the prostate volume is less than 40 cm(3).

PMID- 15265402
TI  - [Effects on erectile function of transplanted major pelvic ganglion into the
      corpus cavernosum of adult rats with bilateral cavernous nerve injury].
AB  - OBJECTIVE: To investigate the effects on erectile function of transplanted major
      pelvic ganglion into the corpus cavernosum of adult male rats undergoing
      transection of bilateral cavernous nerves. METHODS: Twenty-six male Sprague
      Dawley rats (3 - 4 month-old and 300 - 400 g/each) were divided into 2 groups:
      experimental group (transection of bilateral cavernous nerves and transplantation
      of left ganglion into left crus of penis, n = 16) and control group (transection
      of bilateral cavernous nerves only, n = 10). Erectile function was measured by
      injecting APO, and intracavernous pressure was measured 1 and 3 months afterwards
      by electric-stimulating the right major pelvic ganglion or the left crus. Half
      animals in each group were sacrificed 1 and 3 months afterwards for detecting
      nNOS-containing nerve fibers of corpus cavernosum. Electron microscopy of the
      implanted area was performed to assess neuronal survival. RESULTS: Both of the
      two groups have no erectile response to APO injection. Electrostimulation on the
      right major pelvic ganglion and left crus failed to produce erection in
      experimental group. The mean pressure changes in the two groups, measured by
      stimulating the left crus, were (9.41 +/- 3.20) and (4.16 +/- 2.58) cmH(2)O 1
      month afterwards, and (13.67 +/- 4.18) and (5.09 +/- 2.74) cmH(2)O 3 months
      afterwards, respectively (P < 0.05). An increased number of nNOS-containing nerve
      fibers in left crus was detected in experimental group 1 and 3 months later,
      compared with control one (218.7 +/- 24.5, 18.0 +/- 3.7; 183.2 +/- 19.7, 19.0 +/-
      3.8; P < 0.05). Ultrastructure examination by transmission electron microscope
      confirmed the survival of the implanted ganglion. CONCLUSION: Major pelvic
      ganglion can survive in the corpus cavernosum, and it has significant effects on
      the number of nNOS-containing nerve fibers and the alteration of intracavernous
      pressure.

PMID- 15265403
TI  - [PTEN and p27Kip1 have a cooperative role on inhibition proliferation, modulation
      of cell cycle and inducing apoptosis in prostate cancer PC-3 cell].
AB  - OBJECTIVES: To investigate whether the human PC-3 cell infected with recombinant
      Ad-PTEN and Ad-p27Kip1 can steadily produce PTEN and p27Kip1 protein and change
      the biologic behaviors such as cell proliferation, cell cycle and apoptosis. The
      synergistic effect of PTEN and p27Kip1 on the therapy for prostate cancer has
      also been investigated. METHODS: We constructed recombinant adenovirus vector of
      human tumor suppressor gene PTEN and p27Kip1. The viral titer was examined by
      plaque assay and the mRNA and protein expressions of PTEN and p27Kip1 in human
      prostate cancer cell line PC-3 infected with Ad-PTEN and Ad-p27Kip1 were
      determined by RT-PCR and Western blot respectively. MTT assay was used to
      determine the effect of PTEN and p27Kip1 on growth and proliferation of PC-3
      cell; the change of cell cycle and apoptosis was examined by flow cytometry, and
      to compare between the combined therapy group and single gene therapy group.
      RESULTS: The viral titers of Ad-PTEN and Ad-p27Kip1 were 1.8 x 10(7) pfu/ml and
      1.2 x 10(9) pfu/ml respectively. After infected by adenovirus, it had been
      verified that the mRNA and protein expression of PTEN and p27Kip1 were steady in
      human PC-3 cell. Ad-PTEN and Ad-p27 Kip1 inhibited the growth and proliferation
      of PC-3 cells. The progression of cell cycle of PC-3 cell was arrested in G(0)
      G(1) phase, meanwhile the apoptosis rate of PC-3 was also affected after Ad-PTEN
      or/and Ad-p27 Kip1 infected. There was significant difference between combined
      therapy group and single gene therapy group. CONCLUSION: The recombinant Ad-PTEN
      and Ad-p27Kip1 vector were constructed successfully and the expression of
      specific PTEN and p27Kip1 was high, steadily in PC-3 cell line. These results
      suggested that combination of PTEN with p27Kip1 has an application value in
      treatment of prostate cancer in future.

PMID- 15265404
TI  - [The growth inhibition effect of alpha-adrenoceptor antagonists on androgen-
      independent prostate cancer cell line].
AB  - OBJECTIVE: The aim of the present study is to compare the effects of two alpha1
      adrenoceptor antagonist terazosin and alfuzosin together with one alpha
      adrenoceptor antagonist phenoxybenzamine on androgen-independent prostate cancer
      cell lines PC-3 and DU145. METHODS: Two androgen- independent cell lines, PC-3
      and DU145, were used to determine the cell viability, colony-forming ability as
      well as cell cycle characteristics after exposure to these three drugs. RESULTS:
      This study showed that terazosin inhibited not only prostate cancer cell growth
      but also colony-forming ability, which is the main target of clinical treatment.
      On the other hand, alfuzosin and phenoxybenzamine have no effect on cell
      viability and colony forming ability of PC-3 and DU145. In addition, the
      terazosin inhibits cell growth through G(1) phase cell cycle arrest. CONCLUSION:
      This study provided the evidence that alpha1-adrenoceptor antagonist terazosin
      may have a therapeutic potential in the treatment of advanced androgen
      independent prostate cancer.

PMID- 15265405
TI  - [Treatment techniques of harvesting injury of donor renal blood vessels].
AB  - OBJECTIVE: To study the treatment technique for harvesting injury of donor blood
      vessels for the clinic application. METHODS: The data of 32 renal transplantation
      patients with injury of graft blood vessels were retrospectively reviewed. 60
      renal transplantation patients with non-injury during the same term were selected
      as the control group. The treatment techniques for harvesting injury of graft
      blood vessels mainly includes end-to-end anastomosis of graft artery, side-to
      side anastomosis of branch artery, end-to-side anastomosis of branch artery to
      the main renal artery, reconstruction of multiple segmental arteries by using
      iliac arterial grafts from cadaveric donors or recipients on the workbench,
      repairs of injuries for the smaller segmental/polar arteries by using inferior
      epigastric artery, end-to-end anastomosis of the lower thick segmental/polar
      arteries with the iliac internal arterial by placing kidney upside down. RESULTS:
      Those injured included 28 arterial and 4 venous. Average bench surgery time was
      42 minutes. Mean warm ischemic time was 31 minutes. No death occurred at an
      average follow-up of 3.5 years (1 - 5 years). There was no statistical difference
      in the 1-year graft survival, postoperative 1-year acute rejection, delayed graft
      function (DGF) and the incidence of constriction of vascular anastomosis rate
      (96.9%, 12.5%, 21.9%, 3.1%, respectively) compared with non-reconstructed kidneys
      during the same term (98.3%, 11.7%, 18.3%, 1.7%, P > 0.05, respectively).
      CONCLUSION: The flexible and appropriate application of different vascular
      reconstruction means and satisfactory surgery techniques play an important role
      in assuring quality of kidney with harvesting blood vessels injury and donor
      kidney availability.

PMID- 15265406
TI  - [Pharyngo-colonic anastomosis for esophageal reconstruction in the treatment of
      diffuse corrosive esophageal stricture].
AB  - OBJECTIVE: To observe the experience and the outcome of pharyngo-colonic
      anastomosis for esophageal reconstruction in diffuse corrosive esophageal
      stricture involving hypopharynx. METHODS: This retrospective report reviews the
      experience and results of 14 patients who underwent esophageal reconstruction by
      pharyngo-colonic anastomosis without resection of intra thoracic stricture
      esophagus. The left half colonic segment was pulled up to the neck through the
      substernal space in all patients. RESULTS: There was no operative or hospital
      death. Postoperative complications include cervical anastomotic fistula in four
      patients, rupture of the abdominal incision in 1. The length of follow-up ranged
      from half year to 10 years with an average of 4 years. Anastomotic stenosis
      occurred in 2 patients. One case improved after dilatation and the other one
      healed by plastic operation. One patient began to vomit after diet in seven
      months later with barium swallowing the abdominal colon graft was redundant and
      this patient was cured with side by side between the colon and the stomach.
      CONCLUSION: The successful reconstruction for hypo-pharyngo-esophageal stricture
      requires a correct and larger hypopharyngeal opening and a good anastomotic
      technique. From our experience this procedure is shown to be safe and effective.

PMID- 15265407
TI  - [The diagnosis and surgical treatment for 56 cases with pulmonary and pleural
      aspergillosis].
AB  - OBJECTIVE: To summarize the experience of diagnosis and surgical treatment for
      pulmonary and pleural aspergillosis. METHODS: The clinical data of cases with
      pulmonary and pleural aspergillosis were analyzed retrospectively between
      September 1972 and June 2003. There were 53 cases with pulmonary aspergillosis
      and 3 cases with pleural aspergillosis. Aspergillus was found preoperatively in 8
      patients by sputum culture (5 cases) or needle biopsy of the lung (2 cases) or
      fibro-bronchoscopic biopsy (1 case). All patients were treated with surgical
      procedures following X-ray film or CT scan. RESULTS: Of 53 cases with pulmonary
      aspergillosis, 42 lobectomies, 3 segment-Pneumonectomies, and 8 wedge resections
      were performed. Of three cases with pleural aspergillosis following eliminating
      their diseased foci in residual pleural space, two underwent thoracoplasty, one
      underwent postoperative closed chest drainage for one and an half month with
      fluconazole injected into residual pleural space repeatedly for 1 month (200
      mg/100 ml, 1 time per 2 or 3 days). No operative death and major postoperative
      complications occurred. None of the patients had recurrent symptoms at follow-up.
      CONCLUSION: We recommend aggressive surgical resection for pulmonary and pleural
      aspergillosis, and the surgical result is excellent.

PMID- 15265408
TI  - [Postoperative analgesic and anti-inflammatory effects of rofecoxib after total
      knee replacement].
AB  - OBJECTIVE: To evaluate the analgesic efficacy and systemic anti-inflammation of
      preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib,
      after total knee replacement (TKR). METHODS: Thirty patients underwent elective
      knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or
      placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural
      combined isoflurane anesthesia during surgery and patient-controlled epidural
      analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine +
      0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate
      postoperative pain intensity. The outcomes included pain scores during rest and
      movement of knee joints and analgesia satisfaction. Daily morphine consumption
      was recorded. Circulation leucocyte and serum cytokine concentrations (including
      interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were
      determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h
      after surgery in two groups using RIA. The amount of intraoperative blood loss
      and postoperative drainage from the knees were measured. RESULTS: The pain scores
      were significantly less in the group RE than in group E during rest and knee
      joints movement on the first and second postoperative day, with an improvement in
      total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h
      was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = 
      2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than
      in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha
      concentration was significantly lower in group RE than group E at the end of
      surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after
      surgery (P < 0.05). There were no significant differences in respect to the
      amount of intraoperative and postoperative blood loss between two groups (P >
      0.05). CONCLUSION: Preoperative cyclooxygenase-2-specific nonsteroidal anti
      inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid
      requirement and demonstrates a systemic anti-inflammatory effect after TKR.

PMID- 15265409
TI  - [Experimental research of promoting revascularization of tracheal transplantation
      by gene therapy].
AB  - OBJECTIVE: To investigate methods of promoting revascularization of tracheal
      transplantation to increase the length of graft. METHODS: Transfer recombinant
      plasmid pcDNA3.1/myc-His(-)C-bFGF and pCD(2)-VEGF(121) into rabbit cervical
      muscle by direct injection of plasmid following electric pulses in vivo. Use
      histochemistry and immunohistochemistry analysis of muscles injected to show the
      transferred gene expression and the biological effect. Based on the former
      experiment, conduct gene therapy to the rabbit tracheal autotransplantation
      wrapped by cervical combined muscles by injecting plasmid DNA directly, combined
      with gene sutures following electric pulses. Observe and analyze the effect on
      trachea viability. RESULTS: The recombinant plasmid, pcDNA3.1/myc-His(-)C-bFGF
      and pCD(2)-VEGF(121) was transferred into muscles flap in vivo successfully. The
      active protein bFGF and VEGF(121) were expressed at high levels. Blood vessels
      increased significantly in the muscles, and blood circulation was improved by
      local angiogenesis. Ten rings tracheal autograft wrapped by transgenic muscles
      integrating with gene structure revascularized completely, and the rabbit
      survived for a long period of time. There was significant difference between gene
      therapy group and control group (P < 0.01). There was no significant difference
      between bFGF gene therapy group and VEGF(121) gene therapy group. Almost rabbits
      in the control group died of graft necrosis. CONCLUSION: Tracheal grafts
      revascularization can be established early by the cervical combined muscles flap
      wrapping associated with single gene therapy. The length of the tracheal can be
      increased simultaneously.

PMID- 15265420
TI  - [Clinical significance of pancreatic beta-cell function in obese children with
      acanthosis nigricans].
AB  - OBJECTIVE: The strong relation between type 2 diabetes mellitus and obesity with
      acanthosis nigricans is widely concerned. This study investigated the pancreatic
      beta-cell function in obese children with acanthosis nigricans, so as to find out
      the role of insulin secretion and insulin resistance in obese children with
      acanthosis nigricans. METHODS: Thirty-five obese children with acanthosis
      nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were
      enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with
      mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with
      mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups.
      The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were
      measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C
      peptide were calculated. Homeostasis model assessment was applied to assess the
      status of insulin resistance and basic function of pancreatic beta-cell. RESULTS:
      The levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of
      proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin
      secretion index of obese children with acanthosis nigricans, obese control
      children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1
      35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0)
      microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5)
      pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L
      and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9
      (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and
      1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The
      levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of
      proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin
      secretion index in obese children with acanthosis nigricans were significantly
      higher than those in obese children (P < 0.001) and normal children (P < 0.001).
      CONCLUSION: Obese children with acanthosis nigricans had higher insulin
      resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a
      skin sign of high risk of type 2 diabetes mellitus.

PMID- 15265419
TI  - [A pilot study of selective screening for high risk children with inborn error of
      metabolism using tandem mass spectrometry in China].
AB  - OBJECTIVE: The new technology of tandem mass spectrometry is exerting a
      significant impact on the diagnostics of inborn metabolic errors, and allows to
      detect a number of these disorders in a single step. The aim of the present study
      was to establish a dry blood filter paper method for amino acid and acylcarnitine
      profiles test using tandem mass spectrometry and to apply the method for
      selective screening in high risk children with inborn error of metabolism.
      METHOD: The study group consisted of 104 high risk cases of inborn error of
      metabolism from 5 pediatric hospitals in Shanghai and Beijing were tested from
      November 2002 to June 2003; 77 were males and 27 females, the means age was 4.8
      +/- 4.2 years. These patients had mental retardation, slow development,
      psychological abnormalities, muscle hypotonia, jaundice, hepatosplenomegaly,
      recurrent vomiting, and convulsion. Laboratory examinations suggested metabolic
      acidosis, hypoglycemia, hyperammonemia and hyperlactacidemia. Phenylketonuria was
      excluded in this study by routine phenylalanine screening. The control group
      consisted of 308 children, 170 males and 138 females. The blood was collected on
      filter paper, punched and extracted into methanol solution with stable isotope
      labeled internal standards, then derivatized with butanolic-HCl. After
      preparation, the samples were analyzed by tandem mass spectrometry (API 2000).
      RESULTS: Ten of 104 patients (9.6%) were positive in our selective screening
      program, including one with tyrosinemia, one with homocystinuria, one with
      hyperornithinemia, two with methylmalonic acidemia, one with propionic acidemia,
      one with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, two with medium chain
      acyl-CoA dehydrogenase deficiency, and one with carnitine palmitoyl transferase
      type II deficiency. CONCLUSION: The authors established a fast, accurate and
      sensitive tandem mass spectrometry method for amino acid and acylcarnitine
      profiles analysis, nearly 30 metabolic diseases including amino acid disorders,
      organic acid disorders and fatty acid oxidation disorders could be detected, most
      of the diseases that cause death and disability represent preventable entities by
      early diagnosis and treatment. The results indicated the importance of selective
      screening for high risk patients with inborn error of metabolism.

PMID- 15265421
TI  - [Clinical and pathological characterization of antineutrophil cytoplasmic
      antibody associated small vasculitis in children].
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) associated small
      vasculitides (ASV) are rare in children and often complicated in clinical
      manifestations and have very poor prognosis. In order to deepen our understanding
      of ANCA-associated small vasculitis (ASV) in children, the present study aimed to
      characterize their clinical manifestations, serum ANCA and renal
      histopathological findings and outcomes in Chinese children. METHODS: Serum ANCA
      was qualitatively tested with indirect immunofluorescence microscopy and anti
      proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by
      enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to
      investigate the pathological changes. The clinical manifestation, serum ANCA and
      renal histopathological findings and outcome were characterized in 5 children
      with ANCA associated small vasculitis. RESULTS: (1) Five children with ANCA
      associated small vasculitis only accounted for 1.20% of children in whom renal
      biopsy was performed and 0.25% of hospitalized children with renal diseases
      during the same period. The age of onset of the 5 children with ASV was between 8
      to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV
      children were negative for C-ANCA and showed normal anti-proteinase 3 activities,
      but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to
      242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7
      kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide
      spread glomerular crescents formation and capillary tuft fibrinoid necrosis.
      Variety of complement C3 deposits and weak immunoglobulin deposits were noted in
      all ASV but one child who showed relatively strong deposits of IgA and IgM. The
      electronic dense deposits were mainly located in subendothelial space but were
      also found in the glomerular basement membrane in one child. (4) Three children
      with ASV died within one year after diagnosis, and two got remission and restored
      renal function after combined pulse therapy with methylprednisolone and
      cyclophosphamide (CTX), but remained to have hematuria and small amount of
      proteinuria after 1 and 5 year follow-up, respectively. CONCLUSION: Childhood ASV
      was female and P-ANCA predominant, more vulnerable to progress to renal failure
      and poorer in prognosis than adult cases. Qualitative and quantitative ANCA
      measurement and renal biopsy were key to the diagnosis of ASV in children.

PMID- 15265422
TI  - [Clinicopathological analysis of IgA nephropathy with crescentic formation in
      childhood].
AB  - OBJECTIVE: To understand the clinical and pathological characteristics of IgA
      nephropathy (IgAN) with crescentic formation in children. METHODS:
      Clinicopathological data of 29 children with IgAN accompanied by crescents were
      analyzed. These patients were divided into two groups according to the percentage
      of glomeruli affected by crescents more or less than 50%, and their data were
      compared. RESULTS: (1) CLINICAL FEATURES: all the patients had hematuria and
      proteinuria, and macrohematuria (86%) and proteinuria were also common, protein
      excreted in urine was more than 1 g per day in 76% of the patients. The patients
      with edema, hypertension, and renal insufficiency were less than fifty percent.
      Nine patients in Group A (glomeruli affected by crescents > or = 50%) were
      crescentic IgAN. Significantly more cases in Group A had persistent
      macrohematuria, hypertension and renal failure than in Group B (glomeruli
      affected by crescents < 50%) (P < 0.05), with especially severe proteinuria (P <
      0.01). It was easy to find nephritic syndrome in Group A, and asymptomatic
      hematuria combined with proteinuria in Group B. (2) Renal pathology: the
      glomeruli were affected by crescents from 5% to 85%. There were 52% to 85% in
      Group A, and 5% to 40% in Group B. Most crescents were cellular. All the cases
      had a diffuse mesangial proliferation and tubular-interstitial injury to
      different degree. Three cases had crescentic IgAN. Glomerulosclerosis was
      significantly more often seen in Group A (P < 0.05) and tuft adhesion was more
      frequently seen in Group B (P < 0.05). (3) Immunofluorescence: All the patients
      presented deposition of IgA, IgM and C3. There were 45% specimens combined with
      the deposition of IgG. Five cases showed 'full house' (17%), four of them were in
      Group A. None had IgA deposition alone. CONCLUSION: The main clinical feature of
      IgAN with crescentic formation were hematuria combined with proteinuria,
      especially persistent gross hematuria and severe proteinuria. All of them showed
      diffuse mesangial proliferation and tubular-interstitial injury in morphology of
      kidney. Most of them had tuft adhesion. The main type of immunofluorescence were
      IgA + IgM and IgA + IgM + IgG deposition. Some showed 'full house' phenomenon.
      The clinical manifestation and renal lesions of IgAN with diffuse crescentic
      formation were worse than IgAN with glomeruli affected by crescents < 50%.

PMID- 15265423
TI  - [Long-term therapeutic effect of triple therapy consisted of omeperazole,
      clarithromycin and amoxycillin in children with Helicobacter pylori infection and
      approach to re-treatment after failure of the treatment].
AB  - OBJECTIVE: Helicobacter pylori (Hp) infection presents high prevalence in the
      world, but there are few pediatric assays evaluating antimicrobial treatment
      using a short regimen of triple therapy. To evaluate the eradication rate and
      long term therapeutic effect of a triple therapy consisted of omeperazole,
      clarithromycin (CLA) and amoxycillin (AMO) on Hp infection, the authors explored
      the alternative therapeutic programs and their effects after first therapeutic
      failure. METHODS: A total of 192 children with Hp infection were divided into two
      groups: 157 children were given the triple therapy for one week (CLA group); 35
      children were given another triple therapy composed of omeperazole, metronidazole
      (MET) and AMO for two weeks (MET group). All of the children were followed up for
      1 - 36 months after the therapies ended. Twenty-two children in whom Hp was
      eradicated with CLA triple therapy were followed up for 3 years. The children of
      the two groups who had therapeutic failure were given re-treatment as follows.
      CLA triple therapy was given for one week to the children who had failure after
      MET triple therapy; increased doses of CLA with longer treatment course was given
      to the children who had failure after CLA triple therapy. A tetra therapy
      consisted of omeperazole, colloidal bismuth subcitrate (CBS), furazolidone (FUR)
      and AMO was given to the children in whom the re-treatment failed. RESULTS: The
      Hp eradication and ulcer recovery rate of CLA group was 90.4% (142/157) and 96.9%
      (32/33), respectively; the Hp eradication rate of MET group was 77% (27/35).
      There was significant difference between eradication rates of the two groups
      (chi(2) = 4.69, P < 0.05). The recurrence rate of 22 Hp eradicated children
      treated with CLA triple therapy was 4.5% (1/22) during the 3-year follow-up. The
      eradication rate of the three re-treatment programs for 29 children was 75%
      (6/8), 77% (11/15) and 100% (6/6), respectively. CONCLUSION: (1) Omeperazole, CLA
      and AMO triple therapy for one week was the best to eradicate Hp infection with
      high eradication rate, few side effects, short period of treatment, good
      compliance and low recurrence rate. (2) Proper increase of CLA dose and longer
      therapeutic course may increase the eradication rate. Omeperazole, CBA, FUR and
      AMO tetra therapeutic program may be used as an alternative treatment in patients
      who develop resistance to CLA triple therapy.

PMID- 15265424
TI  - [A case with acute pancreatitis complicated with pseudocyst and pancreatic
      ascitis].

PMID- 15265425
TI  - [Association of interferon-gamma + 874 gene single nucleotide polymorphism with
      susceptibility to intrauterine HBV infection].
AB  - OBJECTIVE: To explore the susceptibility of children to develop intrauterine
      hepatitis B virus (HBV) infection through studying the association between
      interferon gamma (IFN-gamma) + 874 single nucleotide polymorphism (SNP) and
      intrauterine HBV infection. METHODS: The subjects were selected from outpatients
      who were in our hepatitis B (HB) vaccine following-up clinics. The subjects whose
      mothers were HBV carriers were inoculated with HB vaccine or HB vaccine and
      hepatitis B immunoglobulin (HBIg). Intrauterine HBV infection was defined as
      peripheral blood HBsAg and/or HBV-DNA positive at birth and lasting for six
      months (group I). Normal immune children were defined as peripheral blood
      negative for HBV marker since birth and afterwards HBsAb titers were above
      protective level (group II). The subjects were composed of the following two
      groups. Group I consisted of 46 children with intrauterine HBV infection. Group
      II was composed of 73 normal children. A Taqman fluorescence polymerase chain
      reaction for the IFN-gamma + 874 SNP was performed for both groups. RESULTS: IFN
      gamma + 874 SNP was tested successfully for every subject. Frequencies of AA, AT
      and TT genotype were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection
      group, and 45.2%, 30.1% and 24.7% in the normal immune children group. A
      significant difference was found in the frequency distribution of IFN-gamma + 874
      genotype between the two groups (chi(2) = 5.102, P = 0.02389). In the
      intrauterine HBV infection group the AA genotype was more common than in normal
      immune group. CONCLUSION: There is an association between IFN-gamma + 874 SNP and
      intrauterine HBV infection. This study suggested the possibility that IFN-gamma +
      874 SNP might be important in determining an individual's susceptibility to
      development of intrauterine HBV infection.

PMID- 15265426
TI  - [Preliminary linkage analysis of a Chinese family with benign familial infantile
      convulsion].
AB  - OBJECTIVE: Benign familial infantile convulsions (BFIC) is a recently recognized
      autosomal dominant inherited disorder. This epileptic syndrome typically begins
      between 3 and 12 months of age with clusters of partial seizures in most cases
      and carries a good prognosis. So far, three loci have been linked to chromosome
      19q12.1-13.1, chromosome 2q24 and chromosome 16p12-q12. The authors performed
      linkage analysis on this pedigree. METHODS: A four-generation Chinese family was
      investigated. The total number of members was 32 in this family and two
      neurologists in Xiangya Hospital gave systemic physical examinations and
      interictal neurological examinations to nineteen members of this family. Venous
      blood samples were taken for genetic analysis. DNA was extracted from peripheral
      blood leukocytes using phenol-chloroform method. Seventeen microsatellite markers
      spanning the critical regions on chromosomes 19q12-13.1, 2q24, and 16p12-q12 were
      genotyped. These markers included D19S49, D19S250, D19S414, D19S416 and D19S245
      for the 19q region, D2S2380, D2S399, D2S111, D2S2195, D2S2330 and D2S2345 for the
      2q region, D16S401, D16S3131, D16S3093, D16S517, D16S3120 and D16S415 for the 16p
      q region. The DNA from each sample was amplified for the 17 markers. After
      polymerase chain reactions (PCR), PCR products of chromosome 19 with markers
      D19S49, D19S250, D19S414, D19S416 and D19S245 were subjected to electrophoresis
      on 8% denatured polyacrylamide gel for at least 2 hours and 20 minutes. Then the
      length of the PCR products was judged in the Strategene Eagle Eye II automated
      gel image analyzer. For the markers from chromosome 2 and 16, PCR products were
      scanned at ABI 377 autosequencer. The data of PCR products were analyzed using
      the software Genescan v3.1, Genetyper v2.1 (Applied Biosystem, CA. USA) and
      GenoDB v1.0. After Mendelian checking, the eligible genotyping data were used for
      linkage analysis. LOD scores were calculated by using MLINK program of LINKAGE
      v5.1, under an assumption of autosomal dominant inheritance and the estimated
      penetrance was 0.9. The allele frequencies of each marker were assumed to be
      equal and the disease-allele frequencies were designated to be 1/10,000. The LOD
      scores were calculated at combination rate (theta) 0.0, 0.1, 0.2, 0.3, and 0.4.
      RESULTS: Among the 17 selected microsatellite markers, which cover the previously
      reported regions, seven markers' data (D16S3131, D16S517, D16S3120, D16S3093,
      D2S2380, D19S250 and D19S414) were omitted due to failed genotyping, low genetic
      heterogeneity, or failure to pass Mendelian checking. Omission of these markers
      was to ensure the reliability of our raw data. The two-point LOD scores were
      below zero for all the markers and the maximum LOD scores at theta = 0.0 were
      less than -2 for markers D19S49, D19S416, D19S245, D16S401, D16S415, D2S399,
      D2S111, D2S2195, D2S2330 and D2S2345. Thus, the linkage result showed no evidence
      that the disease locus is linked to any of these selected markers, which excludes
      the previously reported candidate regions found in other ethnic families.
      CONCLUSION: There is no evidence that this Chinese family was linked to one of
      the following loci: 19q12.1-13.1, 16p12-q12 and 2q24. The results indicated that
      BFIC showed genetic heterogeneity and the Chinese BFIC families might be mapped
      on another new locus.

PMID- 15265427
TI  - [Possible damaging effect of human cytomegalovirus infection on the kidney in
      children].

PMID- 15265428
TI  - [Diagnosis and prognosis of neonatal cerebral infarction].
AB  - OBJECTIVE: To analyze the relationship between clinical characteristics and
      prognosis of neonatal cerebral infarction and to draw attention to the disease to
      improve the long-term outcome through early diagnosis and intervention. METHODS:
      The clinical characteristics of 6 confirmed cases were summarized. Perinatal
      conditions and other factors were analyzed for possible causes of the disease.
      The survived patients were followed-up for 6-8 months. RESULTS: The authors
      diagnosed 6 cases of neonatal cerebral infarction in one year, which accounted
      for 0.6% (6/969) of all the in-patients in the same time period. Among them 3
      cases were confirmed as cerebrovascular malformations by magnetic resonance
      angiography (MRA), In 1 case the infarction was due to severe bilateral
      intraventricular hemorrhage, and in another case the disease was related to
      comprehensive factors such as prematurity, maternal pregnancy induced
      hypertension and respiratory failure secondary to bronchopulmonary dysplasia
      (BPD), and in 1 case the cause was undetermined. Four out of the 6 patients
      presented with varied forms of convulsions, which became the second leading cause
      for all the neonatal convulsive events (20%). None of the patients had localized
      neurological signs in the early course except for abnormal muscular tone of some
      extent. Cerebral ultrasound scanning in 5 out of 6 cases showed positive results.
      The diffusion-weighted magnetic resonance imaging (DW-MRI) was highly valuable
      for early confirmative diagnosis. Only one case was found normal within one year
      of follow-up and all the other 5 cases had unfavorable prognoses of varied
      severity. CONCLUSION: Neonatal cerebral infarction is not a rare condition and
      should be considered as one of the important causes for neonatal convulsion.
      Imaging study is the main technique for diagnosis. The prognoses were poor for
      those cases for whom early diagnosis and treatment can not be made or those with
      widespread cerebral lesions.

PMID- 15265430
TI  - [Report of two cases with lamivudine-caused extrapyramidal reaction].

PMID- 15265429
TI  - [Effect of adenosine on activity of transcription factor NF-kappa B and cytokines
      in myocardial tissue of experimental rats with pneumonia].
AB  - OBJECTIVE: Recent studies have shown that cytokines TNF-alpha and IL-6 play
      important roles in myocardial injury or dysfunction. Transcription nuclear factor
      (NF-kappa B) have been implicated in the regulation of a variety of cytokines in
      response to cellular defense. The authors observed the activity of NF-kappa B and
      cytokines TNF-alpha, IL-6 mRNA expression in myocardium to further investigate
      the mechanism of myocardial injury caused by infectious pneumonia. The
      therapeutic effect of exogenous adenosine was also studied by observing the
      influence on NF-kappa B and cytokines. METHODS: Thirty rats were divided into
      three experimental groups at random, each group had 10 rats. The model of
      pneumonia was induced by the injection of Staphylococcus aureus into the trachea
      of rats. Adenosine-treated rats were given daily slow intravenous injection of
      adenosine at a dose of 150 microg/kg.min for 3 days from the second day. All rats
      were killed on the fifth day. Myocardial tissues were preserved in liquid
      nitrogen for examination. Pathological examination of myocardium was done and TNF
      alpha and IL-6 mRNA expression was detected by reverse transcription polymerase
      chain reaction (RT-PCR). NF-kappa B activity was measured by electrophoretic
      mobility shift assay (EMSA). RESULTS: (1) The myocardium in pneumonia group
      showed significant pathological lesion when compared with control group (P <
      0.01). The pathological lesion of myocardium in adenosine-treated group
      significantly decreased when compared to pneumonia group (P < 0.05). (2)
      Significant increase of TNF-alpha and IL-6 mRNA expression was observed in
      myocardium of pneumonic rats when compared with control group (2.27 +/- 0.27 vs.
      1.05 +/- 0.16; 1.89 +/- 0.31 vs. 1.12 +/- 0.25: P < 0.01, respectively). NF-kappa
      B activity of myocardium in pneumonia group was significantly higher than that in
      control group (13,033 +/- 1286 vs. 383 +/- 15: P < 0.01). (3) TNF-alpha and IL-6
      mRNA expression was significantly decreased in adenosine-treated group when
      compared with pneumonia group (1.25 +/- 0.18 vs. 2.27; 1.31 +/- 0.25 vs. 1.89 +/-
      0.31, P < 0.01, respectively). Comparing to that in pneumonia group, NF-kappa B
      activity of myocardium in adenosine-treated group was significantly decreased (4
      487 +/- 562 vs. 13033 +/- 1286, P < 0.01), but it was still significantly higher
      than that in control group (4487 +/- 562 vs.383 +/- 15, P < 0.01). CONCLUSIONS:
      Increased activity of NF-kappa B and subsequent upregulation of TNF-alpha and IL
      6 mRNA expression probably play a pivotal role in the mechanism of myocardial
      injury in rats with pneumonia. Exogenous adenosine can inhibit inflammatory
      change by lowering NF-kappa B activity and subsequent down-regulation of TNF
      alpha and IL-6 expression. Our findings provide novel therapeutic evidence of
      adenosine in myocardial injury induced by pneumonia in clinic.

PMID- 15265431
TI  - [Cytochrome C release and apoptosis in neonatal rat cerebral hypoxia-ischemia].
AB  - OBJECTIVE: To study the relation of cytochrome C release from mitochondria to
      cytosol and neuronal apoptosis after cerebral hypoxia-ischemia (HI) in neonatal
      rats. METHODS: Hypoxia-ischemia was induced in 7-day-old rat pups by ligation of
      left carotid artery and 7.7% oxygen was inhaled for 55 min. The pups were
      sacrificed and the brains were taken out at different recovery time. Some of the
      brains were homogenized and cellular fraction of mitochondria and cytosol was
      isolated with different speed centrifugation. The cellular fraction was used for
      Western blotting. Some of the brains were sectioned and stained with antibody
      against cytochrome C and TUNEL as well as double labeling with different
      combinations. RESULTS: Western blots showed that cytochrome C in mitochondria was
      not reduced significantly at 1 h, but reduced markedly at 14 h in ipsilateral
      hemisphere post-HI. However, the immunoreactivity of cytochrome C in cytosol was
      increased markedly at 1 h post-HI and reached peak at 14 h post-HI. The number of
      cytochrome C positive cells in the cortex was increased significantly at 1 h (8.4
      +/- 1.8/visual field) compared to normal control (1.5 +/- 0.8/visual field) (P <
      0.01) and reached peak at 14 h (29.0 +/- 5.2/visual field) post-HI. The number of
      TUNEL positive cells increased significantly at 1 h post-HI (14 +/- 3/visual
      field) compared to normal control (1.5 +/- 0.8/visual field) (P < 0.01) and
      reached peak at 24 h (286 +/- 86/visual field). The double labeling of cytochrome
      C and active caspase-3 showed that they colocalized well at 3 h after HI.
      Furthermore, the positive cells showed nuclei condensation. There were more
      active caspase-3 positive cells at late recovery (24 h and on) after HI. The
      double labeling of cytochrome C and TUNEL showed only part of Positive cells
      colocalized. The cells with cytochrome C strong staining showed TUNEL negative or
      weakly positive. The cells with TUNEL strong staining showed weakly cytochrome C
      staining. CONCLUSION: Cytochrome C release is one of the early biochemical
      changes of neuronal apoptosis after hypoxia-ischemia in neonatal rat brain.

PMID- 15265432
TI  - [Time-course of mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expression
      in hypoxic-ischemic neonatal rat brain].
AB  - OBJECTIVE: The cascade of physiological events underlying hypoxic-ischemic brain
      damage (HIBD) remains to be fully established. The perinatal brain shows both an
      increased tolerance to hypoxic-ischemic (HI) injury and a faster and more
      complete recovery than the adult. It is, therefore, important to understand the
      sequence of events following hypoxia and ischemia in young animals. The present
      study aimed to clarify the time-course of the activation of the mu-calpain, and
      the expression of c-Fos, c-Jun, HSP70 and HSP27 proteins following severe HI (2 h
      hypoxia) and their relationship with each other. METHODS: A modified newborn rat
      model of HIBD that included a combination of hypoxia and ischemia as described by
      Rice was used. Forty-two postnatal 7-day-old Sprague-Dawley rats were randomly
      divided into seven groups (6 rats in each): 6 time-window groups and a normal
      control group. Samples were collected at 0, 1, 2, 4, 12 and 24 h after HI
      insults. The protein concentration was determined using a modified Bradford
      assay. mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expressions were
      observed respectively by Western blot from cortical and hippocampal samples.
      RESULTS: The cleavage of cytosolic mu-calpain was observed from both cortical and
      hippocampal samples in neonatal rats after HI. The ratio 76:80 of mu-calpain was
      increased significantly post-HI and reached a maximum at 24 h in cortex and at 12
      h in hippocampus after HI. The expressions of c-Fos and c-Jun from both cortical
      and hippocampal samples in neonatal rats were up-regulated and peaked at 2 or 4 h
      after HI, demonstrating significant differences at 1, 2, 4, and 12 h compared
      with that observed in the control (P < 0.05). When compared with that observed in
      cortex, the nuclear c-Fos expression from hippocampal samples was highly elevated
      at 2, 4 and 12 h but significantly decreased at 24 h after HI (P < 0.05), while
      the nuclear c-Jun expression from hippocampal samples was highly elevated at 0
      and 1 h but significantly decreased at 4 and 24 h after HI (P < 0.05). Similarly,
      the expressions of HSP70 and HSP27 from both cortical and hippocampal samples
      were up-regulated and reached a maximum at 12 or 24 h after HI, demonstrating
      significant differences at 12 or 24 h both in cortex and hippocampus for HSP70,
      and at 24 h in cerebral cortex as well as at 12 and 24 h in hippocampus for HSP27
      compared with the control (P < 0.05). Furthermore, in comparison with that
      observed in cortex, the HSP70 expression from hippocampal samples was highly
      elevated at 1 h, but significantly decreased at 4, 12 and 24 h after HI (P <
      0.05), while the HSP27 expression was permanently elevated in hippocampus after
      HI. CONCLUSION: The neuronal injury induced by HI insults appears to involve many
      ongoing and simultaneous mechanisms. HI activates the calpains immediately, which
      may contribute to neuron apoptosis, and induces a significant brain
      neuroprotection, since there is an increased HSP70 expression and a relatively
      late remarkable HSP27 expression in hypoxic-ischemic neonatal rat brain. Nuclear
      c-Fos and c-Jun may participate in the pathogenesis of HIBD.

PMID- 15265433
TI  - [Exogenous endothelin-1 induced pulmonary hemorrhage in newborn rats and the
      antagonizing effect of calcitonin gene-related peptide].
AB  - OBJECTIVE: To observe the phenomenon of pulmonary hemorrhage (PH) induced by
      exogenous endothelin-1 (exET-1) and the antagonizing effect of exogenous
      calcitonin gene-related peptide (exCGRP) in newborn rats. METHODS: (1) To study
      the exET-1 induced PH: 100 newborn Wistar rats were randomly assigned into
      control group (group A, n = 10) and experiment groups (20 rats in each of groups
      B, C, D and E and 10 in group F). Thirty microl of normal saline and different
      concentrations of exET-1 in saline (ranged from 2 x 10(-6) mol/L to 10 x 10(-6)
      mol/L) were dripped into the rats' trachea through intubation for control group
      and the experiment groups, respectively. (2) To study the antagonizing effect of
      calcitonin gene-related peptide against endothelin: 50 rats were randomly
      assigned into control group (group D(1), n = 10) and experiment groups D(2),
      D(3), D(4) and D(5) (10 rats in each group), and were treated with 30 microl of
      normal saline as control and 4 x 10(-6) mol/L exET-1 via tracheal dripping.
      Twenty microl of exCGRP (concentrations ranged from 6.7 x 10(-8) mol/L to 6.7 x
      10(-6) mol/L) were given by dripping to rats in groups D(3) to D(5) 30 minutes
      after the administration of exET-1. (3) The rats were sacrificed 3 hours after
      the first tracheal dripping and the gross anatomical and histological (HE
      staining) changes in lungs were observed. RESULTS: (1) Following the treatment
      with exET-1, the rats showed cyanosis and dyspnea rapidly. The severity of
      respiratory symptoms varied in a dose dependent fashion with the concentrations
      of exET-1. The symptoms were relieved in the survived rats in about 30 minutes.
      The rats of all exET-1 treated groups presented with different degree of PH and
      group D (treated with 4 x 10(-6) mol/L of exET-1) had the highest incidence
      (diffuse PH 30%, focal PH 25%, spotty PH 25% and 80% in total), with a mortality
      of 20%. Rats in group E and F had lower incidence of PH (50% and 20%) but higher
      mortality (35% and 60%). (2) After the administration of different concentrations
      of exCGRP, the skin of the exET-1 treated rats turned ruddy rapidly with a
      significantly decreased incidence of PH and all the rats survived. The best
      protective effect was observed with the concentration of 6.7 x 10(-6) mol/L, and
      the incidence of PH was reduced to 20% (focal PH 10%, spotty PH 10%). CONCLUSION:
      A significant increase of the endogenous ET-1 in hemorrhagic lung tissue caused
      by rewarming and reoxygenation following hypothermia and hypoxia had been
      confirmed. Administration of intratracheal exET-1 could induce pulmonary
      hemorrhage. This suggests that a significant increase of endogenous ET-1 in lung
      tissue may be one of the mechanisms in pathogenesis of PH caused by rewarming and
      reoxygenation following hypothermia and hypoxia. Endotracheal administration of
      exCGRP showed protective antagonizing effect against PH induced by exET-1. The
      authors speculate that the exCGRP has the potential to treat or even prevent PH
      caused by a significant increase of the endogenous ET-1.

PMID- 15265434
TI  - [Comparison of the effect of ambroxol and dexamethasone on the expression of
      pulmonary surfactant proteins in the fetal rat lungs].
AB  - OBJECTIVE: To investigate the effects of maternally administered dexamethasone
      and ambroxol on the mRNA levels of surfactant proteins (SP-A, SP-B and SP-C)
      expression in fetal rat lungs at gestational age day 19. METHODS: A 19-day fetal
      rat lung model was employed. In situ hybridization was used to detect the
      expression of SP-B mRNA in alveolar type II cell, and the levels of SP-A, SP-B
      and SP-C mRNAs were detected by semi-quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: (1) SP-B mRNA was detected in situ
      in alveolar type II cells in fetal rat lung of day 19 gestational age; (2) In the
      late developmental period of fetal rat lungs, alveolar type II cells were also
      found around bronchus; (3) Comparing to beta-actin mRNA, the relative values of
      SP-A, SP-B and SP-C mRNAs were 0.81 +/- 0.26, 0.97 +/- 0.20 and 0.88 +/- 0.11 in
      fetal lung in the control group. The relative values of mRNAs of SP-A, SP-B and
      SP-C to beta-actin were 1.04 +/- 0.16, 1.28 +/- 0.29, 1.09 +/- 0.25 in fetal
      lungs of the ambroxol injected rats, and were 1.08 +/- 0.25, 1.23 +/- 0.35, 1.21
      +/- 0.25 in fetal lungs of the dexamethasone injected rats, respectively. Both
      ambroxol and dexamethasone-treated rats had significantly higher mRNA expression
      of surfactant proteins compared to the control saline injected animals (P <
      0.05). (4) There were no significant differences between ambroxol and
      dexamethasone in the effects of increasing expressions of surfactant protein
      mRNAs (P > 0.05). CONCLUSION: Antepartum administration of both ambroxol and
      dexamethasone can significantly increase fetal lung SP-A, SP-B and SP-C mRNAs
      expression.

PMID- 15265435
TI  - [Changes of plasma concentration of soluble intercellular adhesion molecule-1 and
      vascular endothelial growth factor in children with Henoch-Schoenlein purpura].

PMID- 15265436
TI  - [Genetic polymorphism and family aggregation of the angiotensin converting enzyme
      in asthmatic children].

PMID- 15265437
TI  - [Relationship between T354P mutation of the human sodium/iodine symporter and
      congenital hypothyroidism].

PMID- 15265438
TI  - [Analysis of 3 cases with nephrotic damage by anti-neutrophil-cytoplasmic
      antibodies associated vasculitis in children].

PMID- 15265439
TI  - [Chronic renal failure in children--report of 65 cases].

PMID- 15265440
TI  - [Analysis of clinical and pathological data in 111 infants and young children
      with glomerular diseases].

PMID- 15265441
TI  - [Clinical analysis of twenty cases with congenital airway abnormalities in
      children].

PMID- 15265442
TI  - [Efficacy of sublingual polyvalent bacterial vaccine (Lantigen B) in children
      with recurrent respiratory infection: a randomized double-blind controlled
      clinical trial].

PMID- 15265443
TI  - [Three cases with acute necrotizing encephalopathy].

PMID- 15265444
TI  - [Clinical diagnosis of tuberous sclerosis complex in 5 children without calcified
      nodule on brain CT].

PMID- 15265445
TI  - [Clinical observation and long-term follow up of benign myoclonus in early
      infancy].

PMID- 15265446
TI  - [Clinical application of nuclide scanning in diagnosis of gastrointestinal
      hemorrhage in children].

PMID- 15265448
TI  - [Metapneumovirus, a newly discovered respiratory pathogen].

PMID- 15265447
TI  - [Report of a case with Alstrom syndrome].

PMID- 15265449
TI  - [Possible relation of leptin with kidney and chronic renal failure].

PMID- 15265450
TI  - [Autoimmune hepatitis in children].

PMID- 15265451
TI  - The Advantage of Bactericidal Drugs in the Treatment of Infection.

PMID- 15265452
TI  - Does Aspirin Prevent Emboli in Infective Endocarditis?

PMID- 15265453
TI  - Intra-arterial Device Infections.
AB  - As an increasing number and variety of prosthetic devices are used in
      cardiovascular medicine, novel infectious complications have been described.
      Infection of intra-arterial devices, including arterial closure devices,
      prosthetic carotid patches, coronary artery stents and endovascular stents, and
      stent-grafts, is now being reported. Prosthetic vascular graft infection is an
      older, more common, and better-characterized entity, but recent developments in
      the surgical management of these infections have prompted a re-examination of the
      syndrome. Staphylococcal species account for most intra-arterial device
      infections, and often, morbidity and mortality rates are high. An update on intra
      arterial device infections is warranted.

PMID- 15265454
TI  - Molecular Methods in the Diagnosis of Endocarditis.
AB  - Advances in molecular microbiologic diagnostics have yielded new tools to
      diagnose infective endocarditis. These tools can detect microorganisms that are
      difficult to grow or are uncultivable, because of prior antimicrobial therapy or
      because of innate characteristics of the microorganisms. This paper reviews
      molecular microbiologic diagnostic techniques and their role in the diagnosis of
      infective endocarditis.

PMID- 15265455
TI  - Fungal Endocarditis.
AB  - Recent advances in medicine have caused fungal endocarditis (FE) to be a more
      common disease entity. Many fungi are potential pathogens in FE, although Candida
      species and Aspergillus species are the most common. Valvular heart disease is
      the necessary underlying condition for FE, with intravenous devices and
      antibiotic use being the predisposing factors for yeast endocarditis, whereas
      immunosuppression in patients with valvulopathy predisposes for mold
      endocarditis. Better prognosis of FE depends on fast and accurate diagnosis and
      subsequent treatment. Echocardiography was the most valuable recent technique in
      the past two decades that allowed early diagnosis of FE and is probably
      responsible for the improved prognosis of patients with FE. In the future,
      development of nonculture-based diagnostic tests may further improve the
      sensitivity, specificity, and rapidity of microbiologic diagnosis of FE. Novel
      approaches in treatment, such as new antifungal drugs, also may assist in
      achieving cure and further improving the prognosis of this disease entity.

PMID- 15265457
TI  - Double-blind Placebo-controlled Trial of Pleconaril in Infants with Enteroviral
      Meningitis.

PMID- 15265456
TI  - Issues in the Management of Endocarditis Caused by Resistant Gram-positive
      Organisms.
AB  - Most cases of infective endocarditis (IE) are caused by gram-positive bacteria
      such as enterococci, streptococci, and staphylococci. Increasing resistance among
      these organisms has eroded the utility of mainstay antibiotics and complicated
      the management of this difficult-to-treat infection. Clinical experience with
      newer gram-positive antibiotics to treat IE is limited.

PMID- 15265458
TI  - Reducing Intracranial Pressure may Increase Survival among Patients with
      Bacterial Meningitis.

PMID- 15265459
TI  - Central Nervous System Lyme Disease.
AB  - Nervous system infection with Borrelia burgdorferi frequently causes meningitis
      and rarely causes encephalomyelitis. Altered cognitive function also can occur in
      the absence of central nervous system infection. Recently developed
      serodiagnostic tools, such as the C6 assay, and appropriate use of Western
      blotting, promise to improve diagnostic accuracy. Treatment trials have
      demonstrated the efficacy of relatively brief courses of oral antimicrobial
      agents, even in peripheral nervous system infection and meningitis. Several well
      performed studies have clearly shown that prolonged antimicrobial treatment of
      "post-Lyme disease" is ineffective. Diagnosis and treatment of Lyme disease
      continue to improve.

PMID- 15265460
TI  - Prion Diseases: Update on Mad Cow Disease, Variant Creutzfeldt-Jakob Disease, and
      the Transmissible Spongiform Encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSEs) are a group of progressive,
      fatal neurodegenerative disorders that share a common spongiform histopathology.
      TSEs may be transmitted in a sporadic, familial, iatrogenic, or zoonotic fashion.
      The putative infectious agent of TSE, the prion, represents a novel paradigm of
      infectious disease with disease transmission in the absence of nucleic acid.
      Several small but spectacular epidemics of TSEs in man have prompted widespread
      public health and food safety concerns. Although TSEs affect a comparatively
      small number of individuals, prion research has revealed fascinating insights of
      direct relevance to common illnesses. This paper reviews recent advances that
      have shed new light on the nature of prions and TSEs.

PMID- 15265461
TI  - Human Herpesvirus 6 Infection of the Central Nervous System.
AB  - Human herpesvirus (HHV) 6 infects all children, usually during the first year of
      life. High fever is the hallmark of primary infection, with febrile seizures the
      most common complication. After primary infection, HHV-6 remains latent or
      persistent at multiple sites, with intermittent reactivation. Many disorders of
      the central nervous system (CNS) have been linked to HHV-6 reactivation,
      including chronic seizure disorders, encephalitis, and demyelinating disorders
      including multiple sclerosis. Although multiple studies have pieced together an
      understanding of the molecular organization, viral characteristics, immunology,
      and epidemiology of HHV-6, the true role of this virus in diseases of the CNS is
      still unfolding.

PMID- 15265462
TI  - Update on the Virologic and Immunologic Response to Highly Active Antiretroviral
      Therapy.
AB  - Highly active antiretroviral therapy (HAART) delays clinical progression by
      suppressing viral replication, measured by a substantial reduction in HIV RNA,
      allowing the immune system to reconstitute, measured in most studies by an
      increase in CD4 cells. These virologic and immunologic consequences do not occur
      uniformly among HAART users. Markers of HIV disease stage at the time of HAART
      initiation are critical determinants of the progression while receiving HAART. In
      this report, we review studies describing the heterogeneous virologic and
      immunologic progression after the initiation of HAART, discuss methodologic
      concerns in the study of the response of biomarkers, and update findings obtained
      in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of
      antiretroviral therapy, and age at the time of initiation are independent
      determinants of response.

PMID- 15265463
TI  - New Antiretroviral Agents for the Treatment of HIV Infection.
AB  - Issues, such as complexity, tolerability, and drug resistance and cross
      resistance, limit the effectiveness of current antiretroviral regimens and make
      the continued development of newer agents important, despite the availability of
      20 approved drugs for the treatment of HIV infection. Many new compounds are in
      development in existing classes: nucleoside and nucleotide analogue reverse
      transcriptase inhibitors (eg, D-d4FC and SPD754), non-nucleoside analogue reverse
      transcriptase inhibitors (eg, capravirine and TMC125), and protease inhibitors
      (eg, tipranavir and TMC114). In addition, newer classes of antiretroviral drugs,
      such as HIV entry inhibitors (eg, TNX-355, SCH 417690, UK-427,857, AMD 11070),
      that target the first step in the HIV life cycle are under development. Continued
      improvement in the treatment of HIV infection will result from the availability
      of convenient, well-tolerated, and affordable drugs with potent and durable
      antiretroviral activity.

PMID- 15265464
TI  - Endothelial dysfunction, inflammation, and insulin resistance: a focus on
      subjects at risk for type 2 diabetes.
AB  - Subjects with obesity, family history of type 2 diabetes, polycystic ovary
      syndrome, previous gestational diabetes, dyslipidemia, hypertension, impaired
      glucose tolerance or impaired fasting glucose, and those with metabolic syndrome
      are at risk for the development of type 2 diabetes. Some of them are also at risk
      for cardiovascular disease. Some underlying abnormalities such as insulin
      resistance, endothelial dysfunction, and low-grade chronic inflammation are
      frequently present and closely associated in all these groups. The flow of
      substrates, hormones, and cytokines from visceral fat to skeletal muscle and to
      the endothelial cells, along with some genetic abnormalities that lead to
      impaired insulin action in the peripheral tissues and to impaired insulin
      stimulated nitric oxide production in endothelial cells, may play a role in
      establishing these shared metabolic and vascular derangements. Weight loss,
      thiazolidinediones, and metformin improve vascular function in subjects at risk
      for type 2 diabetes and may prove to reduce cardiovascular events in these
      individuals.

PMID- 15265465
TI  - Oxidative stress and diabetic vascular complications.
AB  - Vascular complications of diabetes represent the leading cause of morbidity and
      mortality in affected patients. Production of reactive oxygen species is
      increased in diabetic patients, especially in those with poor glycemic control.
      Reactive oxygen species affect vascular smooth muscle cell growth and migration,
      endothelial function, including abnormal endothelium-dependent relaxation and
      expression of a proinflammatory phenotype, and modification of the extracellular
      matrix. All of these events contribute to the development of diabetic
      microvascular and macrovascular complications, suggesting that the sources of
      reactive oxygen species and the signaling pathways that they modify may represent
      important therapeutic targets.

PMID- 15265466
TI  - Nutrition and the endothelium.
AB  - Growing evidence suggests that dietary factors play an important role in
      modulating endothelial function. Epidemiologic and clinical studies have related
      intake of alpha-linolenic acid and long-chain n-3 fatty acids to lower plasma
      concentrations of inflammatory cytokines and endothelial adhesion molecules, both
      of which are considered markers of endothelial dysfunction. In contrast, trans
      fatty acid intake and a higher dietary glycemic load have been associated with
      increased plasma concentrations of these biomarkers. Recently, several
      epidemiologic and intervention studies have examined the relationship between
      overall dietary patterns and endothelial dysfunction. In general, a "prudent
      diet," characterized by higher intake of fruits, vegetables, legumes, fish,
      poultry, and whole grains, is associated with a beneficial effect on the
      endothelium. Conversely, a "Western diet," characterized by higher intake of red
      and processed meats, sweets, desserts, French fries, and refined grains, is
      associated with an impairment of the endothelial function. These findings provide
      additional biological mechanisms through which dietary factors influence the risk
      of cardiovascular diseases.

PMID- 15265469
TI  - Nutrition and pregnancy: the link between dietary intake and diabetes.
AB  - Pregnancy is a time when serial metabolic changes in the mother are carefully
      regulated to provide optimum substrate to both mother and fetus. Subtle
      perturbations in maternal metabolism can have implications not only for the index
      pregnancy, but also for future generations. The literature provides evidence that
      maternal nutrition plays a major role in the destiny of the offspring. Both
      maternal malnutrition and overnutrition are associated with subsequent diabetes
      in the offspring. Pregnancy represents a window of opportunity for health care
      providers to change dietary patterns toward habits that will be healthier for the
      individual now, as well as impacting on the future. The challenge for clinicians
      is to provide nutritional information based on scientific evidence that
      facilitates the normalization of fetal nutrition, and thus minimize the risk that
      the child will develop diabetes.

PMID- 15265470
TI  - Insulin sensitivity and premenstrual syndrome.
AB  - Maintaining normal blood glucose levels is a constant challenge for women with
      diabetes. Anecdotal reports reveal that many women question if menstrual cycle
      phases may affect their blood glucose levels. However, results from studies
      investigating the effect of the menstrual cycle on insulin sensitivity in
      diabetic women have been conflicting. One variable that may account for the
      conflicting results is the presence or absence of premenstrual syndrome (PMS),
      which may exacerbate menstrual cycle-related effects on insulin sensitivity.
      Treatment of PMS with serotonin reuptake inhibitors may alleviate the symptoms of
      PMS, as well as improve insulin sensitivity and help regulate blood glucose
      levels.

PMID- 15265471
TI  - Determinants of fetal growth.
AB  - Fetal growth is the end product of a variety of genetic, maternal, fetal, and
      placental factors. Maternal size is a dominant determinant of birth weight.
      Specific nutrients and their availability modify the expression of genetically
      determined metabolic and transfer systems. Hormones and growth factors of
      maternal, fetal, and placental origin regulate nutrient transfer and fetal organ
      development. Fetal development is ultimately determined by dynamic interactions
      between all of these factors beginning prior to conception and proceeding to
      delivery.

PMID- 15265472
TI  - Treatment of type 1 diabetes with anti-T-cell agents: from T-cell depletion to T
      cell regulation.
AB  - Studies in animal models of type 1 diabetes had suggested that the disease was
      due to an immune-mediated destruction of insulin-producing cells. As this
      understanding was developed, clinical trials that were directed against T cells
      were begun, because these lymphocytes were thought to be the primary mediators of
      disease. Initial studies used broad-spectrum agents and showed general efficacy
      in either preventing the loss of insulin secretion or reducing the need for
      exogenous insulin. Although encouraging, the enthusiasm for this approach waned
      due to the lack of long-term effects and toxicities. These studies were followed
      by trials with more specific agents, but the issue of toxicity remained. Newer
      agents, such as anti-CD3 antibody, are also targeted against T cells but the
      toxicity and efficacy of modified anti-CD3 antibody, for example, appears to be
      improved over previously tested agents. In addition, our understanding of the
      immunologic effects of anti-T-cell agents has evolved. Data now suggest that
      efficacy and duration of the effects of anti-T-cell drugs can be enhanced when
      the agents provoke immune modulation rather than depletion of effector cells.

PMID- 15265473
TI  - Generation of surrogate beta cells from tissue stem cells.
AB  - beta-Cell replacement represents a promising approach for the treatment of type 1
      diabetes, but is limited by donor shortage and recurring autoimmunity. Stem and
      progenitor cells, which can be expanded and differentiated in vitro, may offer an
      abundant source of cells for transplantation. The difficulty of expanding mature
      beta cells and their pancreatic precursors has turned the attention to the
      potential of cells from other tissues to function as surrogate beta cells. Recent
      research has shown that cells from a number of tissues can be induced to produce,
      process, and store insulin, release it in response to physiologic signals, and
      replace beta-cell function in rodents. The change in cell phenotype has been
      induced by dominant transcription factor genes ectopically expressed in the
      cells, or following cell exposure to differentiation factors in vitro or in vivo.
      Propagation of these cells in tissue culture provides an opportunity for further
      modifying them to enhance their resistance to immune destruction.

PMID- 15265475
TI  - Evolving surgical strategies for pancreas transplantation.
AB  - Pancreas transplant has become a reliably predictable treatment and cure for
      patients with type 1 diabetes mellitus and hypoglycemic unawareness or renal
      failure. During the past 2 years, the use of enteric drainage has been shown to
      decrease morbidity over traditional bladder drainage, and the use of the portal
      system for venous drainage continues to be explored. Technically, the use of
      circular staplers, over a hand-sown anastomosis for duodenal drainage, has gained
      popularity, and alternative arterial reconstruction methods have been developed.
      Living donor pancreas and kidney transplants are also becoming more common
      throughout the world. In the area of immunosuppression, steroid-free protocols,
      now commonplace in kidney transplants, are being applied successfully to pancreas
      transplantation. Finally, the benefit of solitary pancreas and pancreas after
      kidney transplantation has been questioned, and a more complete analysis of
      pancreas alone and pancreas after kidney transplants is anticipated in the near
      future.

PMID- 15265474
TI  - Risks and side effects of islet transplantation.
AB  - Islet transplantation can deliver stable glycemic control, relief from recurrent
      severe hypoglycemia, and insulin independence. Accessing the portal vein via the
      percutaneous hepatic approach carries the risk of bleeding, and the infusion of
      islets a risk of portal vein thrombosis. In the long term, common minor problems
      with immunosuppression are mouth ulcers, diarrhea, and acne. Longer-term risks
      include malignancy and serious infection, both rare to date in clinical islet
      transplantation. Sensitization to donor antigens may also occur. The long-term
      diabetes complications may stabilize, but of this aspect little is known to date.
      In the short term, there may be some elevation of serum cholesterol and blood
      pressure, in some patients there has been a decline in renal function, and in a
      few, acute retinal bleeds. For most, improvement in glucose control with
      resolution of glycemic lability and hypoglycemia has been a net benefit.

PMID- 15265476
TI  - Effects of high carbohydrate and high fat diet on plasma metabolite levels and on
      i.v. glucose tolerance test in intact and neutered male cats.
AB  - To elucidate the impact of dietary influence on carbohydrate and lipid metabolism
      and on the development of diabetes mellitus in the carnivorous cat, a 3 weeks
      feeding trial was carried out on six sexually intact and six neutered adult male
      cats. The effects of two isonitrogenic diets, differing in carbohydrate and fat
      content, were investigated on plasma metabolite levels in a 24-h blood sampling
      trial. Plasma leptin concentrations were also determined at the beginning and at
      the end of the 24-h trial. Glucose and insulin response was measured in an i.v.
      glucose tolerance test. A 5 days long digestion trial was also performed, which
      revealed a high digestion capacity of both fat and carbohydrates in cats. The
      high fat diet induced a significant rise in the plasma triglyceride, FFA, beta
      hydroxybutyrate and cholesterol concentration, while the elevation in the glucose
      level did not reach significance. In the glucose tolerance test no significant
      difference was found between the neutered and intact cats. However, independently
      of the sexual state, the cats on the high fat diet showed a slightly elongated
      glucose clearance and reduced acute insulin response to glucose administration.
      This is indicative of diminished pancreatic insulin secretion and/or beta-cell
      responsiveness to glucose. The results of this preliminary study may be the
      impetus for a long-term study to find out whether it is rather the fat rich
      ration than carbohydrate rich diet that is expected to impair glucose tolerance
      and thus might contribute to the development of diabetes mellitus in cats.
      Whether the alteration in glucose metabolism is due to altered leptin levels
      remains to be determined.

PMID- 15265477
TI  - Oral glucosamine and the management of feline idiopathic cystitis.
AB  - Oral glucosamine was compared to a placebo for the management of cats with feline
      idiopathic cystitis (FIC) in a randomised, double-blinded, placebo-controlled,
      study. Forty cats with a history of recurrent cystitis due to FIC were divided
      into two groups and treated daily per os with either 125 mg N-acetyl glucosamine
      or a placebo for six months. Owners graded their cats' clinical signs at the
      beginning and end of the study, and kept daily diaries documenting signs of
      cystitis using visual analogue scales. Further episodes of cystitis were seen in
      26 (65%) of the cats during the study. Affected cats experienced a mean of five
      recurrences (range 1-19) with each recurrence lasting a mean of four days (range
      1-64 days). There were no significant differences between the two groups when
      considering the owners assessments of the mean health score (P>0.5), the average
      monthly clinical score (P=0.22) or the average number of days with clinical signs
      (P=0.28). Two cats suffered from such severe recurrent urethral obstruction that
      they were euthanased; they were both in the placebo group. Compared to the start
      of the study the majority of cats in both groups improved significantly (P<0.001)
      (mean health score of each group at the start was 0.5+/-SD 0.5, compared to
      glucosamine 4.4+/-0.7 and placebo 3.9+/-1.6 at the end). This is believed to have
      occurred because the owners of 36 of the 40 cats (90%) started feeding more
      canned cat food. The urine specific gravity at the start of the trial was
      significantly higher (mean 1.050+/-SD 1.007) than when reassessed one month later
      (1.036+/-1.010, P<0.01).

PMID- 15265478
TI  - Feline lower airway disease: a retrospective study of 22 naturally occurring
      cases from Greece.
AB  - In this retrospective study of 22 cats with lower airway disease of either
      intermittent (23%) or persistent nature (77%), the Siamese breed (55%) was
      significantly over-represented. Females (68%) were slightly but not significantly
      over-represented. No significant association was found between the clinical stage
      of disease and the physical findings, thoracic radiographic changes or the
      response to treatment. Cough, the most common presenting complaint, was the only
      symptom detected in the cats with intermittent disease, yet the two most severely
      affected animals did not show it. Thoracic auscultation did not reveal any
      abnormality in 41% of the cats. Haematology revealed eosinophilia in 46% of the
      cats. A bronchial pattern was the most common radiographic abnormality (73%),
      followed by alveolar (32%) and interstitial patterns (23%). Interestingly,
      thoracic radiographs were normal in 23% of the cats. The combination of short
      term corticosteroids and bronchodilators resulted in complete and long-term
      remission of symptoms in nine cats, while the other 11 required ongoing
      medication because of relatively frequent relapses. One of the remaining two cats
      died during an asthmatic crisis, while the other was lost to follow up.

PMID- 15265479
TI  - PCR studies of feline leprosy cases.
AB  - 16S rRNA gene sequence analysis provided evidence for two different mycobacterial
      species, Mycobacterium lepraemurium and a potentially novel species, as causative
      agents of 'feline leprosy'. Comparison of 16S rRNA gene sequence data obtained
      for M. lepraemurium and the potentially novel species indicated 12 nucleotide
      differences over a 446 bp region encompassing the V2 and V3 hypervariable
      regions. From available 16S rRNA gene sequence data, M. lepraemurium shared
      greatest nucleotide identity with M. avium subsp paratuberculosis and M. avium.
      The novel species had a long helix 18 in the V3 region and shared greatest
      nucleotide identity with M. leprae, M. haemophilum and M. malmoense. The novel
      species had an additional 'A' nucleotide at position 105 of the aligned 16S rRNA
      gene sequence, the only other mycobacterial database sequence having this same
      extra nucleotide being M. leprae. This nucleotide variation was exploited to
      develop specific PCR assays for the two species. These were found to be effective
      and specific when tested against a panel of mycobacteria including species found
      in feline leprosy lesions and closely related mycobacteria and also when applied
      directly to formalin-fixed, paraffin-embedded tissues from feline leprosy cases.

PMID- 15265480
TI  - Investigation of nasal disease in the cat--a retrospective study of 77 cases.
AB  - A retrospective study was undertaken to determine the prevalence of different
      diseases in cats referred for investigation of chronic nasal disease, to identify
      historical, clinical and diagnostic features which may assist in making a
      diagnosis, and to provide information pertaining to outcome in these cats.
      Diagnoses included neoplasia (30 cases), chronic rhinitis (27), foreign body (8),
      nasopharyngeal stenosis (5), Actinomyces infection (2), nasal polyps (2),
      stenotic nares (2), and rhinitis subsequent to trauma (1). The most common
      neoplasia was lymphosarcoma (21 cases), with a median survival of 98 days for
      cats treated with multiagent chemotherapy. Cats with neoplasia were older on
      average than the other cats, and were more likely to be dyspnoeic and have a
      haemorrhagic and/or unilateral nasal discharge than cats with chronic rhinitis.
      Cats with neoplasia were more likely to have radiographic evidence of nasal
      turbinate destruction, septal changes, or severe increases in soft tissue density
      than cats with chronic rhinitis. It was unusual for cats with diseases other than
      neoplasia to be euthanased as a result of their nasal disease.

PMID- 15265481
TI  - Disorders of the parathyroid glands.
AB  - The three calcitropic hormones, parathyroid hormone (PTH), 1,25
      dihydroxycholecalciferol and calcitonin are together responsible for calcium
      homeostasis in the mammal. Feline PTH is an 84 amino acid, single chain
      polypeptide with a molecular weight of 9449, which is secreted by the parathyroid
      glands. The principle secretagogue for PTH is a low plasma ionised calcium
      concentration, although both 1,25-dihydroxycholecalciferol and phosphate have
      significant roles in regulating PTH secretion. The ability to accurately measure
      circulating PTH in the cat has simplified the evaluation of disorders of calcium
      metabolism in this species. In primary parathyroid disorders the lesion is
      located within the parathyroid gland, with parathyroid secretion being
      inappropriate to the prevailing mineral balance. By contrast, in secondary
      conditions a pathological state out with the parathyroid gland alters mineral
      homeostasis and the parathyroid gland responds in an appropriate manner. The
      measurement of circulating PTH may then be used to determine if PTH secretion is
      appropriate to the prevailing calcium concentrations to differentiate primary
      from secondary disorders. Although primary hyper and hypoparathyroidism are
      generally considered rare endocrine conditions of the cat, the ability to measure
      PTH has led to their increasing recognition.

PMID- 15265482
TI  - Concurrent Fusarium chlamydosporum and Microsphaeropsis arundinis infections in a
      cat.
AB  - A 7-year-old cat was presented initially with multiple draining sinuses on the
      metatarsal region of its right hindlimb. Another lesion had appeared at the same
      time on the fifth proximal interphalangeal joint of the left forelimb.
      Histopathological examination of a biopsy from the right hindlimb lesion revealed
      chronic pyogranulomatous inflammation associated with yeast-like bodies and
      septate mycelia; a fungus was cultured on conventional media but not identified
      further. Culture of a swab collected from the left forelimb lesion demonstrated a
      pigmented fungus, also not characterised further. Although there was initially a
      favourable response to ketoconazole (Nizoral, Janssen-Cilag Pty. Ltd) and beta
      lactam therapy, the infection in the hind limb relapsed subsequently, and
      Fusarium chlamydosporum was cultured from deep biopsy specimens. Clinical
      improvement followed debridement and itraconazole (Sporanox, Janssen-Cilag Pty.
      Ltd; 100 mg orally once daily), however amputation of the limb represented the
      best chance for a cure. The cat made an uncomplicated recovery following surgery
      and remained well for five months until the lesion on the left forelimb recurred.
      Amputation of the distal fourth digit was then performed, and the resected tissue
      submitted for culture. The dematiaceous fungus Microsphaeropsis arundinis was
      subsequently cultured. The cat remained well for several months, until a further
      F. chlamydosporum infection developed on the body wall. This was excised 7 months
      ago, and no lesions have recurred in this area. Importantly, this is the first
      reported case of M. arundinis infection in a mammalian host.

PMID- 15265483
TI  - Feline necrotising sialometaplasia: a report of two cases.
AB  - Unilateral swelling of submandibular salivary gland in two cats was diagnosed as
      necrotising sialometaplasia. Histological features that differentiate the disease
      from other salivary gland lesions, particularly neoplasia are: lobular necrosis
      of salivary tissue; squamous metaplasia conforming to duct and/or acinar
      outlines; preservation of salivary lobular morphology; and variable inflammation
      and granulation tissue.

PMID- 15265484
TI  - Surgical management of acute ear canal separation in a cat.
AB  - A 5-year-old cat presented with haemorrhagic left aural discharge, 2 days
      following a road traffic accident. Otoscopic examination identified disruption of
      the external ear canal at the auricular/annular cartilage junction. This was
      managed by total ear canal ablation and lateral bulla osteotomy. Left sided
      facial nerve deficits were present following surgery. Eighteen months
      postoperatively there were no auricular problems, however facial nerve deficits
      persisted. There are no previous reports describing management of acute
      separation at the auricular/annular cartilage junction of the external ear in the
      cat or dog. This case report describes the presentation, diagnosis and surgical
      management of an acute ear canal separation at the auricular/annular junction of
      the external ear canal in a cat.

PMID- 15265485
TI  - C(17,20)-lyase inhibitors. Part 2: design, synthesis and structure-activity
      relationships of (2-naphthylmethyl)-1H-imidazoles as novel C(17,20)-lyase
      inhibitors.
AB  - A series of 1- and 4-(2-naphthylmethyl)-1H-imidazoles (3 and 4) has been
      synthesized and evaluated as C(17,20)-lyase inhibitors. Several 6-methoxynaphthyl
      derivatives showed potent C(17,20)-lyase inhibition, suppression of testosterone
      biosynthesis in rats and reduction in the weight of prostate and seminal vesicles
      in rats, whereas most of these compounds increased the liver weight after
      consecutive administrations. The effect on the liver weight was removed by
      incorporation of a hydroxy group and an isopropyl group at the methylene bridge,
      as seen in (S)-28d and (S)-42. Selectivity for C(17,20)-lyase over 11beta
      hydroxylase is also discussed, and (S)-42 was found to be a more than 260-fold
      selective inhibitor. Furthermore, (S)-42 showed a potent suppression of
      testosterone biosynthesis after a single oral administration in monkeys. These
      data suggest that (S)-42 may be a promising agent for the treatment of androgen
      dependent prostate cancer.

PMID- 15265486
TI  - Synthesis and DNA binding affinity of novel A-C8/C-C2-exo unsaturated alkoxyamido
      linked pyrrolo[2,1-c][1,4]benzodiazepine dimers.
AB  - The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1
      c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA
      binding affinity and they also exhibit moderate anticancer activity.

PMID- 15265487
TI  - Potent histone deacetylase inhibitors: N-hydroxybenzamides with antitumor
      activities.
AB  - The screening tests of N-hydroxybenzamides for their HDAC-inhibitory activities
      led to the discovery of the promising compounds with a 2-naphthylcarbonyl group
      and with a 1,4-biphenylcarbonyl group. These compounds were further modified to
      optimize their physico-chemical profile. As a result, the inhibitor with a 6
      amino-2-naphthylcarbonyl was obtained, which showed not only promising growth
      inhibitions against a panel of tumor cells, but also an improved water
      solubility. It exhibited the maximal 185% of survival rate (%T/C) in a in vivo
      experiment with P388 cell-inoculated mice.

PMID- 15265488
TI  - Synthesis and biological characterization of novel hybrid 7-[[2-(4-phenyl
      piperazin-1-yl)-ethyl]-propyl-amino]-5,6,7,8-tetrahydro-naphthalen-2-ol and their
      heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors.
AB  - In a recent preliminary communication we described the development of a series of
      hybrid molecules for the dopamine D2 and D3 receptor subtypes. The design of
      these compounds was based on combining pharmacophoric elements of aminotetralin
      and piperazine molecular fragments derived from known dopamine receptor agonist
      and antagonist molecules. Molecules developed from this approach exhibited high
      affinity and selectivity for the D3 receptor as judged from preliminary
      [(3)H]spiperone binding data. In this report, we have expanded our previous
      finding by developing additional novel molecules and additionally evaluated
      functional activities of these novel molecules in the [(3)H]thymidine
      incorporation mitogenesis assay. The binding results indicated highest
      selectivity in the bioisosteric benzothiazole derivative N6-[2-(4-phenyl
      piperazin-1-yl)-ethyl]-N6-propyl-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine
      (14) for the D3 receptor whereas the racemic compound 7-([2-[4-(2,3-dichloro
      phenyl)-piperazin-1-yl]-ethyl]-propyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-ol
      (10c) showed the strongest potency. Mitogenesis studies to evaluate functional
      activity demonstrated potent agonist properties in these novel derivatives for
      both D2 and D3 receptors. In this regard, compound 7-[[4-(4-phenyl-piperazin-1
      yl)-butyl]-prop-2-ynyl-amino]-5,6,7,8-tetrahydro-naphthalen-2-ol (7b) exhibited
      the most potent agonist activity at the D3 receptor, 10 times more potent than
      quinpirole and was also the most selective compound for the D3 receptor in this
      series. Racemic compound 10a was resolved; however, little separation of activity
      was found between the two enantiomers of 10a. The marginally more active
      enantiomer (-)-10a was examined in vivo using the 6-OH-DA induced unilaterally
      lesioned rat model to evaluate its activity in producing contralateral rotations.
      The results demonstrated that in comparison to the reference compound
      apomorphine, (-)-10a was quite potent in inducing contralateral rotations and
      exhibited longer duration of action.

PMID- 15265489
TI  - Design, synthesis, and conformational analysis of eight-membered cyclic
      peptidomimetics prepared using ring closing metathesis.
AB  - As part of a program to identify novel scaffolds that adopt defined secondary
      structure when incorporated into peptides, we have designed and prepared a
      library of constrained eight-membered ring lactams based upon 7-amino-8-oxo
      1,2,3,6,7-pentahydroazocine-2-carboxylic acid. Ring closing metathesis (RCM) was
      employed as the key step, proceeding in high yields to afford the Z olefin. In
      this reaction sequence, the first generation benzylidene ruthenium RCM catalyst
      was superior to the second-generation imidazoline catalyst, which gave extensive
      oligomerization at higher concentrations. Conformational analysis of the 2S,7S
      and 2R,7S stereoisomers revealed that the 2R,7S isomer is a Type VIa beta-turn in
      the solid state (X-ray crystal structure) and in water (NMR analysis). The Type
      VIa beta-turn is relatively rare, typically bearing the cis amide bond found in
      proline-containing sequences. The 2S,7S diastereomer has an extended geometry of
      the pendent amide chains. The corresponding saturated derivatives (7-amino-8
      oxoazocane-2-carboxylic acid) were also synthesized and investigated. The 2S,7S
      azocane bears an extended geometry and mimics the C(+) conformer of ox-[Cys-Cys],
      found in a variety of naturally occurring peptides. The scaffolds described here
      are useful for the design of constrained peptidomimics with defined secondary
      structure.

PMID- 15265490
TI  - Antibacterial prenylflavone derivatives from Psoralea corylifolia, and their
      structure-activity relationship study.
AB  - Three new prenylflavonoids, namely corylifols A-C (1-3), together with 13 known
      ones, were isolated from the seeds of Psoralea corylifolia. Their structures were
      elucidated by spectral methods including 1D and 2D NMR techniques. All the
      isolates were tested on antibacterial assays, and nine of them showed significant
      antibacterial activities against two pathogenic bacteria Staphylococcus aureus
      and S. epidermidis. The antibacterial structure-activity relationship of these
      prenylflavonoids (1-16) was also briefly discussed.

PMID- 15265491
TI  - Estradiol derivatives bearing sulfur-containing substituents at the 11beta or
      7alpha positions: versatile reagents for the preparation of estrogen conjugates.
AB  - Estradiol derivatives bearing HS-, HSCH(2)-, HSCH(2)CH(2)-, MeS-, MeSCH(2)-,
      MeSCH(2)CH(2)-, or PhCH(2)SCH(2)CH(2)-groups at the 11beta position or an HS
      group at the 7alpha position have been synthesized, and their binding affinity to
      the estrogen receptor (ER) determined. Nearly all of these substituted estrogens
      retain high binding affinity, and at the 11beta position, the sulfur atom has an
      effect on ER binding that is similar to that of a carbon atom. These thiol
      derivatives are promising intermediates for the preparation of a variety of
      estradiol conjugates. The methyl sulfides, in particular, might potentially be
      developed as (11)C-labeled agents for imaging ER-positive tumors by positron
      emission tomography.

PMID- 15265492
TI  - The synthesis and immunosuppressive activities of steroid-urotoxin linkers.
AB  - The urotoxins (Glu-Asp-Gly-OH, His-Gly-Glu-OH, His-Gly-Lys-OH, and His-Gly-Lys
      NHNH(2)) were introduced into the convenient sites of hydrocortisone and
      prednisolone via the amidation or condensation reactions to form the
      corresponding linkers 7a-d, 8a-d, 9a,b, and 10a,b in acceptable yields. The
      bioassays such as prolongation of heterotopic transplanted cardiac tissue
      survival in vivo, inhibitory effects on phagocytosis of mouse peritoneal
      macrophages and concanavalin (ConA) or lipopolysaccharide (LPS) induced
      proliferation of mouse spleen lymphocytes in vitro show that at the comparable
      concentrations the immunosuppressive activities of the steroid-urotoxin linkers
      7a-d, 8a-d, 9a,b, and 10a,b were higher than that of hydrocortisone,
      prednisolone, and the urotoxins alone, as well as significantly higher than that
      of the mixture of hydrocortisone and urotoxins or prednisolone and urotoxins. The
      so-called 'permissive action' may be responsible for the enhancement of the
      mentioned bioactivities of the steroid-urotoxin linkers 7a-d, 8a-d, 9a,b, and
      10a,b.

PMID- 15265493
TI  - Icogenin, a new cytotoxic steroidal saponin isolated from Dracaena draco.
AB  - This paper reports on the cytotoxic effect induced by a new natural steroidal
      saponin, icogenin, on the myeloid leukemia cell line HL-60. Icogenin was found to
      be a cytotoxic compound IC(50) 2.6+/-0.9microM at 72h, with growth inhibition
      caused by the induction of apoptosis, as determined by microscopy of nuclear
      changes and the fragmentation of poly(ADP-ribose) polymerase-1.

PMID- 15265494
TI  - Synthesis and nematocide activity of S-glycopyranosyl-6,7-diarylthiolumazines.
AB  - 6,7-Diaryl derivatives of mono and di-S-glycopyranosylthiolumazine derivatives 5
      8 were prepared to test their nematocide activity. In vitro tests against
      Caenorhabditis elegans were performed and it was found that monosubstituted
      derivatives 5-7 showed higher activity than the corresponding unsubstituted 2
      thiolumazines 1-3, whilst 2-S,4-S-di-glycopyranosylpteridine derivative 8 was
      inactive in contrast to unsubstituted derivative 4. In order to check whether the
      lack of activity of 8 was due to the two bulky substituents of the pteridine
      nucleus, 2-S,4-S-dimethyl derivative 9 was synthesized and assayed showing also
      lack of activity. A theoretical study on the stability of the different possible
      tautomers of compound 4 was carried out in an attempt to explain some, in
      appearance, anomalous (13)C NMR data of this compound.

PMID- 15265495
TI  - Novel 18beta-glycyrrhetinic acid analogues as potent and selective inhibitors of
      11beta-hydroxysteroid dehydrogenases.
AB  - Extensive structural modifications to the 18beta-glycyrrhetinic acid template are
      described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase
      isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors
      have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo
      18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective
      inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC(50) = 4pM.

PMID- 15265496
TI  - Synthesis of novel thiazolothiazepine based HIV-1 integrase inhibitors.
AB  - Thiazolothiazepines are among the smallest and most constrained inhibitors of
      human immunodeficiency virus type-1 integrase (HIV-1 IN) inhibitors (J. Med.
      Chem. 1999, 42, 3334). Previously, we identified two thiazolothiazepines lead IN
      inhibitors with antiviral activity in cell-based assays. Structural optimization
      of these molecules necessitated the design of easily synthesizable analogs. In
      order to design similar molecules with least number of substituent, herein we
      report the synthesis of 10 novel analogs. One of the new compounds (1) exhibited
      similar potency as the reference compounds, confirming that a thiazepinedione
      fused to a naphthalene ring system is the best combination for the molecule to
      accommodate into the IN active site. Thus, the replacement of sulfur in the
      thiazole ring with an oxygen does not seem considerably affect potency. On the
      other hand, the introduction of an extra methyl group at position 1 of the
      polycyclic system or the shift from a thiazepine to an oxazepine skeleton
      decreased potency. In order to understand their mode of interactions with IN
      active site, we docked all the compounds onto the previously reported X-ray
      crystal structure of IN. We observed that compounds 7-9 occupied an area close to
      D64 and Mg(2+) and surrounded by amino acid residues K159, K156, N155, E152,
      D116, H67, and T66. The oxygen atom of the oxazolo ring of 7 and 8 could chelate
      Mg(2+). These results indicate that the new analogs potentially interact with the
      highly conserved residues important for IN catalytic activities.

PMID- 15265497
TI  - TOPS-MODE based QSARs derived from heterogeneous series of compounds.
      Applications to the design of new anti-inflammatory compounds.
AB  - A new application of TOPological Sub-structural MOlecular DEsign (TOPS-MODE) was
      carried out in anti-inflammatory compounds using computer-aided molecular design.
      Two series of compounds, one containing anti-inflammatory and the other
      containing nonanti-inflammatory compounds were processed by a k-means cluster
      analysis in order to design the training and prediction sets. A linear
      classification function to discriminate the anti-inflammatory from the inactive
      compounds was developed. The model correctly and clearly classified 88% of active
      and 91% of inactive compounds in the training set. More specifically, the model
      showed a good global classification of 90%, that is, (399 cases out of 441).
      While in the prediction set, they showed an overall predictability of 88% and 84%
      for active and inactive compounds, being the global percentage of good
      classification of 85%. Furthermore this paper describes a fragment analysis in
      order to determine the contribution of several fragments towards anti
      inflammatory property, also the present of halogens in the selected fragments
      were analyzed. It seems that the present TOPS-MODE based QSAR is the first
      alternate general 'in silico' technique to experimentation in anti-inflammatory
      discovery.

PMID- 15265498
TI  - Novel glycine transporter type-2 reuptake inhibitors. Part 1: alpha-amino acid
      derivatives.
AB  - A variety of alpha-amino acid derivatives were prepared as glycine transport
      inhibitors and their ability to block the uptake of [(14)C]-glycine in COS7 cells
      transfected with human glycine transporter-2 (hGlyT-2) was evaluated. An array of
      substituents at the chiral center was studied and overall, L-phenylalanine was
      identified as the preferred amino acid residue. Compounds prepared from l-amino
      acids were more potent GlyT-2 inhibitors than analogs derived from the
      corresponding d-amino acids. Introducing an achiral amino acid such as glycine,
      or incorporating geminal substitution in the alpha-position, led to a significant
      reduction in GlyT-2 inhibitory properties.

PMID- 15265499
TI  - Novel glycine transporter type-2 reuptake inhibitors. Part 2: beta- and gamma
      amino acid derivatives.
AB  - Several beta- and gamma-amino acid derivatives were prepared as glycine transport
      inhibitors and their ability to block the uptake of [(14)C]-glycine in COS7 cells
      transfected with human glycine transporter-2 (hGlyT-2) were evaluated. A range of
      lipophilic side chains were tolerated in the beta-amino acid series (i.e., Ph,
      CH(2)Ph, CH(CH(3))(2), and CH(2)CH(CH(3))(2)). In the gamma-amino acid series,
      minimal differences in potency were observed between the alpha,beta-unsaturated
      analogs and the corresponding saturated derivatives. In both series, a 4-biphenyl
      or 4-phenoxyphenyl substituent appended to the urea or cyanogunaidine moiety was
      necessary for in vitro activity.

PMID- 15265500
TI  - Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological
      activity of benzoylpiperidine derivatives.
AB  - A series of benzoylpiperidine analogs related to 4a was prepared, and their
      ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with
      human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes
      to the benzoylpiperidine region of the molecule led to a significant decrease in
      GlyT-2 inhibitory activity. In contrast, the distal aryl ring was more tolerant
      to functional group modifications and could accommodate a variety of substitutes
      at the C-2 or C-3 positions. Comparable activities to 4a were obtained by
      replacing the anilino nitrogen with an ether linkage 27 or by exchanging the
      isopropoxy ether moiety with an isopropyl amino group 15. A distinct preference
      for a 2-carbon tether (n=1) was observed relative to the corresponding 3-carbon
      homolog (n=2).

PMID- 15265501
TI  - Synthesis and biological evaluation of novel fluoro and iodo quinoline
      carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies.
AB  - In order to develop radioligands of human NK-3 receptor (hNK-3r) for imaging
      studies by positron emission tomography (PET) or single photon emission computed
      tomography (SPECT), a new series of fluoro- and iodo-quinoline carboxamides were
      synthesized and evaluated in a target receptor binding assay. Compared to the
      unsubstituted parent compound SB 223 412 (Ki=27 nM +/- 9), affinity was not
      altered for the analogues 1c and 2c bearing a fluorine in position 8 (Ki
      approximately 24-27 nM), and was only slightly reduced for compounds 1b, 2b, 1e
      and 2e fluorinated or iodinated at the position 7 (Ki approximately 49-67 nM). A
      drastic reduction in binding (Ki > 115 nM) was observed for all other halogenated
      compounds 1a, 2a, 1d, 2d, 1f and 2f.

PMID- 15265502
TI  - A critical structural determinant of opioid receptor interaction with phenolic 5
      phenylmorphans.
AB  - The opioid receptor binding affinities of N-methyl- and N-phenethyl-5
      phenylmorphans with a meta-hydroxy substituent [3-(2-methyl-2
      azabicyclo[3.3.1]non-5-yl)-phenol (1a), and 3-(2-phenethyl-2-azabicyclo[3.3.1]non
      5-yl)-phenol (1b)] were compared with the affinities of four new ligands bearing
      an ortho- or para-hydroxyl substituent (2-(2-methyl-2-azabicyclo[3.3.1]non-5-yl)
      phenol (2a) and 2-(2-phenethyl-2-azabicyclo[3.3.1]non-5-yl)-phenol (2b), 4-(2
      methyl-2-azabicyclo[3.3.1]non-5-yl)-phenol (3a), and 4-(2-phenethyl-2
      azabicyclo[3.3.1]non-5-yl)-phenol (3b)) that were synthesized from 2-bromoanisole
      or the known 2-methyl-5-phenyl-2-azabicyclo[3.3.1]nonane (13), respectively. The
      data indicated that either the electronic state of the phenolic ring is critical
      for the ligand's interaction with an opioid receptor, or that there must be a
      specific distance and angle for a hydrogen bond between the phenolic moiety and
      an amino acid in the binding domain that cannot be altered.

PMID- 15265503
TI  - Microscopic techniques as potential tools to quantify the extent of bioadhesion
      of liquid systems.
AB  - This work demonstrates the potential of fluorescence and confocal microscopy as
      techniques to quantify both the extent and duration of bioadhesion of alginate
      solutions to porcine oesophageal tissue using an in vitro model. The retention of
      low (40 kDa), medium (240 kDa) and high (416 kDa) MW alginates was quantified via
      three methods of analysis. Fluorimetric analysis of the dose removed from the
      oesophageal surface suggested that the percentage of the original dose retained
      at 30 min was 7.9 +/- 7.0%, 21.9 +/- 9.5% and 23.7 +/- 5.8% for the alginates in
      order of increasing MW. Analysis of the dose adhered at 30 min using fluorescence
      microscopy demonstrated that 5.5 +/- 1.9%, 7.1 +/- 2.7% and 18.2 +/- 1.7% of the
      original dose of the alginate solutions was retained at 30 min. The results found
      using confocal microscopy showed that the percentage of the original dose adhered
      at 30 min of the low, medium and high MW alginates were 4.5 +/- 1.9%, 7.2 +/-
      5.3% and 11.8 +/- 4.3%, respectively. All techniques demonstrated significantly
      greater retention of the high MW solution at 30 min compared to the low MW
      solution. Both confocal and fluorescence microscopy may be used as techniques to
      evaluate the bioadhesion of liquid systems.

PMID- 15265504
TI  - Assessment and modulation of acamprosate intestinal absorption: comparative
      studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo models.
AB  - The purpose of this study was to explore the intestinal absorption mechanism of
      acamprosate and to attempt to improve the bioavailability (BA) of the drug
      through modulation of its intestinal absorption using two enhancers (polysorbate
      80 and sodium caprate) based on in situ, in vitro and in vivo models and
      comparing the results obtained. Intestinal transport of the drug, in the absence
      and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13
      and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell
      monolayers. Additionally, the effect of sodium caprate on drug oral
      bioavailability, measured as urinary recovery, was quantified by performing in
      vivo experiments with the rat as animal model. Only sodium caprate was able to
      increase the absorption rate constant (ka) of acamprosate in the mid-intestine of
      the rats from 0.29 +/- 0.07 h-1 in the absence of the promoter to 0.51 +/- 0.19 h
      1 in the presence of C10 16 mM, along with the apparent permeability (Papp)
      obtained in Caco-2 cells (around two-fold). However, the drug bioavailability in
      rats (around 20%) did not improve in the presence of any of the concentrations
      tested (13, 16 and 50 mM). It is concluded that acamprosate absorption likely
      occurs via paracellular pathway and can be enhanced by sodium caprate in situ and
      in vitro but not in vivo-thus suggesting that although in situ and in vitro
      studies could be useful in early screening to select a potential promoter, in
      vivo studies in animal models are necessary to confirm the utility of the
      enhancer and to determine the influence of physiological variables.

PMID- 15265505
TI  - Cystatin incorporated in poly(lactide-co-glycolide) nanoparticles: development
      and fundamental studies on preservation of its activity.
AB  - Preservation of biological activity is still a major challenge for successful
      formulation and delivery of protein drugs. Cystatin, a potential protein drug in
      cancer therapy, was incorporated in poly(lactide-co-glycolide) nanoparticles by
      the water-in-oil-in-water emulsion solvent diffusion technique. In order to
      preserve the biological activity of cystatin, a specific modification of the
      method of producing nanoparticles was introduced. The activity of cystatin was
      strongly influenced by the stirring rate during preparation and, to a lesser
      extent, by selected organic solvents. A synergistic effect of mechanical stirring
      and sonication, both at low energy levels, enabled nanoparticles to be formed
      without denaturing the cystatin. Nanoparticles produced by the optimised method
      ranged from 300 to 350 nm in diameter with 85% of the starting cystatin activity.
      The loading efficiency of cystatin depends on polymer type and ranged from 12 to
      57%, representing an actual loading of 0.6-2.6% (w/w). Among various cryo
      /lyoprotectants bovine serum albumin was identified as the most successful. The
      use of a protein protectant prior to nanoparticle formation was essential to
      maintaining the biologically active three-dimensional structure of cystatin. In
      addition, a specific type of poly(lactide-co-glycolide) polymer, particularly in
      terms of its functional groups, was identified to be important in retaining
      cystatin activity. Cystatin incorporated into nanoparticles in this way maintains
      its structural integrity, making it suitable for effective drug delivery.

PMID- 15265506
TI  - PAMPA--a drug absorption in vitro model 11. Matching the in vivo unstirred water
      layer thickness by individual-well stirring in microtitre plates.
AB  - Many plate-based in vitro assays of membrane permeability (e.g., Caco-2, MDCK,
      PAMPA) of sparingly soluble candidate molecules report permeability of water, and
      not of the intended membrane barrier. This is so because the unstirred water
      layer on both sides of the membrane barrier is rate limiting for these highly
      permeable molecules. The thickness of this water layer can be 1500-4000 microm in
      unstirred assays. Under in vivo conditions, however, the unstirred water layer is
      believed to be 30-100 microm thick. Lightly stirred in vitro assays, using plate
      shakers, cannot lower the thickness of the water layer to match that found in
      vivo. In this study, 55 lipophilic drugs were employed to characterize the effect
      of stirring in parallel artificial membrane permeability assay (PAMPA). Highly
      efficient individual-well magnetic stirring at speeds greater than 110 rpm has
      been demonstrated to lower the unstirred water layer thickness to the in vivo
      range. Stirring at 622 rpm has lowered the layer thickness to 13 microm in some
      cases, which had not been previously achieved for plate-based permeability
      assays. With diminished water layer contribution at 622 rpm, for example, the
      effective permeability of progesterone is 2754 x 10(-6) cm/s. The new stirring
      apparatus used in this study is not only suitable for PAMPA, but can also be used
      in Caco-2 assays. Because of the diminished resistance of the thinner water
      layer, the stirred PAMPA permeation time has decreased from the usual 15 h to
      about 15 min for lipophilic compounds.

PMID- 15265507
TI  - Phase behaviour analysis of solid dispersions of loperamide and two structurally
      related compounds with the polymers PVP-K30 and PVP-VA64.
AB  - The purpose of the present study was to investigate the influence of the
      structure of a poorly water soluble model drug (loperamide) on the phase
      behaviour in solid dispersions with PVP-K30. Dispersions with PVP-VA64, a less
      hydrophilic polymer, were investigated as well in order to study the influence of
      differences in polymer structure and water content of the samples. The solid
      dispersions of PVP-K30 or PVP-VA64 with loperamide as well as with two fragments
      of this molecule were prepared by spray drying. The amount of residual solvents
      and water was determined with GC and thermogravimetric analysis (TGA). The drug
      loading of the dispersions was determined using high performance liquid
      chromatography (HPLC). The solid state properties were evaluated using powder
      XRD, IR-spectroscopy and MT-DSC. All mixtures containing loperamide proved to be
      completely amorphous, whereas the dispersions containing the fragments are only
      amorphous in case the polymer content is high. The phase diagrams that were
      constructed clearly show that loperamide exhibits a different behaviour in the
      solid dispersions than its two building blocks. They also point to the presence
      of specific intermolecular compound--polymer interactions in the dispersions of
      one of the fragments with the two polymers. This was confirmed by the IR-results.
      Despite structural similarities, interactions in dispersions containing
      loperamide are far less important. In dispersions containing high concentrations
      of the other fragment, the DSC curves give indications for polymorphism whereas
      IR and XRD-spectra point towards inclusion of solvent in these samples.

PMID- 15265508
TI  - Accuracy of calculated pH-dependent aqueous drug solubility.
AB  - The aim of the present study was to investigate the extent to which the Henderson
      Hasselbalch (HH) relationship can be used to predict the pH-dependent aqueous
      solubility of cationic drugs. The pH-dependent solubility for 25 amines, carrying
      a single positive charge, was determined with a small-scale shake flask method.
      Each sample was prepared as a suspension in 150 mM phosphate buffer. The pH
      dependent solubility curves were obtained using at least 10 different pH values.
      The intrinsic solubility, the solubility at the pKa and the solubility at pH
      values reflecting the pH of the bulk and acid microclimate in the human small
      intestine (pH 7.4 and 6.5, respectively) were determined for all compounds. The
      experimental study revealed a large diversity in slope, from -0.5 (celiprolol) to
      -8.6 (hydralazine) in the linear pH-dependent solubility interval, which is in
      sharp contrast to the slope of -1 assumed by the HH equation. In addition, a
      large variation in the range of solubility between the completely uncharged and
      completely charged drug species was observed. The range for disopyramide was only
      1.1 log units, whereas that for amiodarone was greater than 6.3 log units,
      pointing at the compound specific response to counter-ion effects. In conclusion,
      the investigated cationic drugs displayed compound specific pH-dependent
      solubility profiles, indicating that that the HH equation in many cases will only
      give rough estimations of the pH-dependent solubility of drugs in divalent buffer
      systems.

PMID- 15265509
TI  - Kinetics of degradation and oil solubility of ester prodrugs of a model dipeptide
      (Gly-Phe).
AB  - Oil-based depot formulations may constitute a future delivery method for small
      peptides. Thus, a requirement is attainment of sufficient oil solubility for such
      active compounds. A model dipeptide (Gly-Phe) has been converted into lipophilic
      prodrugs by esterification at the C-terminal carboxylic acid group. The
      decomposition kinetics of octyl ester of Gly-Phe (IV) has been investigated at pH
      7.4 (37 degrees C) and IV was shown to degrade by first-order kinetics via two
      parallel pathways (1) intramolecular aminolysis resulting in formation of a 2,5
      diketopiperazine and (2) hydrolysis of the ester bond producing the dipeptide.
      The cyclisation reaction was dominating in the decomposition of methyl (II) butyl
      (III) octyl (IV) decyl (V) and dodecyl (VI) esters of Gly-Phe at pH 7.4. However,
      this degradation pathway was almost negligible for pH below 6. During degradation
      of the dipeptide esters in 80% human plasma pH 7.4 (37 degrees C) a minimal
      amount of cyclo(-Gly-Phe) was formed. A faster degradation of the esters in 80%
      human plasma pH 7.4 compared to those in aqueous solution pH 7.4 was suggested to
      be due to fast cleavage of the peptide bond. Low oil solubilities for Gly-Phe and
      the hydrochlorides of the dipeptide esters III and VI were observed. Although the
      solubility of Gly-Phe in oil solutions was enhanced by hydrophobic ion pairing
      with sodium decyl sulfonate the oil solubility was still less than 1 mg Gly
      Phe/ml. By addition of a solubiliser, 10% N,N-dimethylacetamide (DMA), to
      Viscoleo the solubility of the HIP complexes increased significantly. The present
      study indicates that sufficient oil solubility might only be obtained for
      relatively small peptides by using the prodrug approach in combination with
      solubility enhancing organic solvents like DMA.

PMID- 15265510
TI  - The influence of guaifenesin and ketoprofen on the properties of hot-melt
      extruded polyethylene oxide films.
AB  - Films containing polyethylene oxide (PEO) and a model drug, either guaifenesin
      (GFN) or ketoprofen (KTP), were prepared by hot-melt extrusion. The thermal
      properties of the hot-melt extruded films were investigated using differential
      scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to
      examine the surface morphology of the films, and wide angle X-ray diffraction
      (XRD) was used to investigate the crystalline properties of the polymer, drugs
      and physical mixtures as well as the solid state structure of the films. The
      stability of the polymer was studied using gel permeation chromatography. The
      mechanical properties, including percent elongation and tensile strength of the
      films, were determined on an Instron according to American Society for Testing
      Materials (ASTM) procedures. The Hansen solubility parameter was calculated using
      the Hoftyzer or van Krevelen method to estimate the likelihood of drug--polymer
      miscibility. Both GFN and KTP were stable during the extrusion process. Melting
      points corresponding to the crystalline drugs were not observed in the films.
      Crystallization of GFN on the surface of the film was observed at all
      concentrations studied, however KTP crystallization did not occur until reaching
      the 15% level. Guaifenesin and ketoprofen were found to decrease drive load,
      increase PEO stability and plasticize the polymer during extrusion. The Hansen
      solubility parameters predicted miscibility between PEO and KTP and poor
      miscibility between PEO and GFN. The predictions of the solubility parameters
      were in agreement with the XRD and SEM results. The percent elongation decreased
      with increasing GFN concentrations and significantly increased with increasing
      levels of KTP. Both GFN and KTP decreased the tensile strength of the extruded
      film.

PMID- 15265511
TI  - Metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted.
AB  - Generally, 70-80% of absorbed nicotine is mainly metabolized to cotinine by
      cytochrome P450 (CYP) 2A6. There is genetic polymorphism in the human CYP2A6
      gene. Among several mutated alleles, CYP2A6*4 allele is a whole deleted type. The
      purpose of the present study was to clarify the metabolic profile of nicotine in
      subjects whose CYP2A6 gene is deleted. We developed a liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method for nicotine and its nine metabolites.
      Excretion levels of nicotine and its metabolites in 24 h accumulated urine after
      the chewing of one piece of nicotine gum were evaluated in five Japanese subjects
      whose CYP2A6 genotype was determined. In three subjects with CYP2A6*1A/CYP2A6*1A,
      CYP2A6*1A/CYP2A6*1B, and CYP2A6*1A/CYP2A6*4 (group I), nicotine was mainly
      excreted as cotinine, trans-3'-hydroxycotinine, and their glucuronide
      (approximately 60%). In contrast, in two subjects with CYP2A6*4/CYP2A6*4 (group
      II), trace levels of cotinine, cotinine N-glucuronide, and cotinine 1'-N-oxide
      were detected. Trans-3'-hydroxycotinine and its O-glucuronide were not detected.
      The excretion levels of nicotine itself, nicotine N-glucuronide, and nicotine 1'
      N-oxide were higher than those in the other three subjects. The total excretion
      levels of these three compounds were approximately 95% in group II versus 35% in
      group I. However, the sum of the excretion levels of nicotine and all metabolites
      was similar among these five subjects. This is the first report of the metabolic
      profile of nicotine in subjects whose CYP2A6 gene is deleted.

PMID- 15265512
TI  - Non-invasive monitoring of phenytoin by reverse iontophoresis.
AB  - Transdermal iontophoresis offers a non-invasive sampling method for therapeutic
      drug monitoring. This study examined whether iontophoretic extraction (a) is
      concentration dependent, (b) reflects the subdermal level of unbound drug, (c)
      follows protein binding changes, and (d) becomes truly non-invasive when a co
      extracted compound is used as an internal standard for calibration. Iontophoresis
      was conducted in vitro using dermatomed pig-ear skin. The subdermal solution was
      a buffer containing phenytoin at therapeutic concentrations, an internal standard
      at fixed level, human albumin and/or valproic acid. The ionized form of phenytoin
      was recovered at the anode by electro-migration, while the neutral form was
      extracted to the cathode by electroosmosis. A satisfactory correlation between
      the reverse iontophoretic extracted amount of phenytoin and the subdermal
      concentration was observed. Iontophoresis extracted only the free fraction of
      phenytoin. At steady state, reverse iontophoresis monitored changes in free drug
      concentration provoked in the subdermal compartment. Acetate was introduced at a
      fixed concentration into the subdermal compartment to act as an 'internal
      standard'. Subsequently, acetate and the ionized form of phenytoin were co
      extracted to the anode. The ratio of the extracted amounts was proportional to
      the subdermal concentration ratio demonstrating a means by which the method may
      become truly non-invasive.

PMID- 15265513
TI  - Cellular disposition of arabinogalactan in primary cultured rat hepatocytes.
AB  - To characterize a targeting property of arabinogalactan (AG) as a carrier to the
      liver, we examined cellular disposition, such as binding and internalization in
      primary cultured rat hepatocytes, comparing them to those of asialofetuin (AF). A
      tyramine derivative of AG was synthesized to allow labeling with 125I. Binding of
      AG to the cells was concentration-dependent and saturable. The number of binding
      sites (n) of AG on the cell surface was 4.0 x 10(5) +/- 0.1 x 10(5) sites per
      cell which was about similar to that of AF. The value of Ka of AG was 2.2 x 10(8)
      +/- 0.1 x 10(8) M-1 being seven-fold higher than that of AF. The binding of AG
      was competitively inhibited by AF and was decreased by calcium depletion. These
      results indicate that AG can bind strongly to hepatocytes probably through the
      recognition by the asialoglycoprotein receptor (ASGP-R). Both 125I-labeled AG and
      fluorescein-labeled AG were internalized into the cells. The rate of
      internalization of AG was faster than that of AF, indicating that AG is
      effectively endocytosed. Microscopic observations showed that FITC labeled AG
      accumulated in granules within the primary cultured rat hepatocytes. Subcellular
      fractionation indicated that the internalized AG was mainly associated with the
      lysosomal fraction. However, the internalized AG seemed to remain intact in the
      hepatocytes. In conclusion, we found that AG is effectively internalized in
      primary cultured rat hepatocytes. Although AG seems a good candidate for
      targeting to the liver due to its high affinity binding and rapid
      internalization, it remains to be established whether the apparent lack of
      biodegradation will result in cytotoxic effects at chronic administration in
      vivo.

PMID- 15265514
TI  - NMR studies of the inclusion complex between beta-cyclodextrin and paroxetine.
AB  - A 1H and 13C NMR study on the inclusion complex of paroxetine with beta
      cyclodextrin was carried out in order to define the stoichiometry of the
      association and its strength. Proton and carbon chemical shift measurements of
      paroxetine and beta-cyclodextrin were performed at several molar ratios and
      temperatures, allowing the determination of a 1:1 stoichiometry and an
      association constant value of the order of 2 x 10(3) for the paroxetine-beta
      cyclodextrin complex. Overhauser effects in the rotating frame were also
      measured, and the experimental interproton distance constraints have been used
      for molecular model building of the complex. The obtained model indicates that
      the benzodioxolyl moiety of paroxetine is deeply inserted in the cavity of the
      cylindrical structure of beta-cyclodextrin, while the fluoro-phenyl ring lays
      above the wider rim.

PMID- 15265515
TI  - Comparative therapeutic efficacy of a novel lyophilized amphotericin B lecithin
      based oil-water microemulsion and deoxycholate-amphotericin B in immunocompetent
      and neutropenic mice infected with Candida albicans.
AB  - The in vivo efficacy of a new amphotericin B (AmB) oil-in-water lecithin-based
      microemulsion delivery system (M-AmB) compared to deoxycholate-AmB (D-AmB) was
      studied in an immunocompetent and neutropenic murine model of systemic
      candidiasis. D-AmB was administered at the maximum tolerated dose of 1 mg/kg
      whereas M-AmB was given at the doses of 1, 2 and 3 mg/kg; doses were well
      tolerated due to their reduced toxicity. Both formulations were administered 24,
      48 and 72 h after infection in immunocompetent mice, and 2, 6 and 24 h after
      infection in neutropenic mice. Kaplan-Meier survival curves showed that the M-AmB
      treated group had a better survival time than infected mice without treatment
      used as a control group (P = 4.66 x 10(-6)), and the Mann-Whitney W statistical
      test indicated that it reduced the percentage of mortality and fungal load in the
      most representative organs. This new formulation is a designed competitor which
      has proved to present better results than D-AmB in an established infection not
      only in immunocompetent but in neutropenic mice as well.

PMID- 15265516
TI  - Virosome and ISCOM vaccines against Newcastle disease: preparation,
      characterization and immunogenicity.
AB  - The purpose of this study was to prepare and characterize virosomes and ISCOMs
      containing envelope proteins of Newcastle disease virus (NDV) and to evaluate
      their immunogenicity in target animals (chickens). Virosomes were prepared by
      solubilization of virus with either Triton X-100 or octyl glucoside (OG) followed
      by detergent removal. Biochemical analysis revealed that these virosomes
      contained both the haemagglutinin-neuraminidase protein (HN) and the fusion
      protein (F), with preserved biological activity. Acidic environment triggered the
      fusion between virosomes and chicken erythrocyte ghosts. Formation of ISCOMs was
      achieved by solubilizing phospholipids, cholesterol, envelope protein antigen and
      Quil A in Triton X-100. The ISCOM particles were formed by removal of the
      detergent. In each formulation the relative HN content correlated with the
      capability to agglutinate red blood cells. The immunogenicity of these lipid
      based subunit vaccines was determined in chickens after subcutaneous
      immunization. The relative HN content of the subunit vaccines correlated with the
      haemagglutination-inhibition (HI) antibody titres. Virosomes prepared with Triton
      X-100 and ISCOMs offered high clinical protection (> 80%) upon challenge with
      virulent NDV. Virosomes prepared with OG yielded lower clinical protection
      despite high HI antibody titres. Virosomes with reduced antigen density showed
      poor immunogenicity and protection. In conclusion, ND virosomes and ISCOMs were
      found to be immunogenic and provided good protection.

PMID- 15265517
TI  - Different HPMC viscosity grades as coating agents for an oral time and/or site
      controlled delivery system: a study on process parameters and in vitro
      performances.
AB  - Currently, delayed/pulsatile release and colon delivery represent topics of
      remarkable interest. The present paper deals with the study and development of an
      oral dosage form devised to release drugs following a programmed time period
      after administration or, when opportune design modifications are introduced, to
      target the colon. The system is composed of a drug-containing core and a
      hydrophilic swellable polymeric coating capable of delaying drug release through
      slow interaction with aqueous fluids. An optional external gastroresistant film
      is applied to overcome gastric emptying variability, thus allowing colon delivery
      to be pursued according to the time-dependent approach. The aim of this work was
      to evaluate different hydroxypropyl methylcellulose (HPMC) viscosity grades as
      possible materials for the attainment of the system retarding hydrophilic layer.
      Both the relevant suitability for application onto tablet cores by aqueous spray
      coating in fluid bed and capability of delaying drug release for a programmable
      period were explored and compared. Methocel E50 was found to afford the best
      balance among different important items, i.e. process time, retarding ability,
      dimensions of the coated units and possibility of finely tuning the delay
      duration. Further results pointed out the robustness of Methocel E50-based
      systems, which have shown to be practically unaffected by the concentration of
      the employed coating solution and the pH of the release medium, as well as only
      poorly influenced by ionic strength, at least with regard to values encompassed
      in the physiological range for gastrointestinal fluids.

PMID- 15265518
TI  - A novel compression-coated doughnut-shaped tablet design for zero-order sustained
      release.
AB  - A novel coated doughnut-shaped tablet is evaluated as to its ability to be
      manufactured in a reproducible manner, and as to whether it releases model drugs
      at a zero-order rate. The doughnut-shaped tablets were compressed using specially
      designed punches, which make automated production feasible. In the preliminary
      part of the experiment, HPMC K15M mixed with gelatin was found to be the most
      suitable coating tablet material with respect to its disintegration and adherence
      properties. The adherence of the coating tablet to ibuprofen cores was not
      optimal, so different concentrations of gelatin, to act as a plasticiser and
      enhance adherence, were further investigated. Friability results of the coated
      doughnut-shaped tablet indicate that coating tablets containing 20% and 30%
      gelatin had a percentage weight losses of less than 1% after 100 revolutions in a
      Roche friabilator. For all the concentrations of gelatin, the granule blends had
      angle of repose values in the range of 22.01-17.8 degrees. The compressibility
      factor, as measured from the slopes of the natural logarithm of compressional
      force versus crushing strength, were 121.91 +/- 2.36, 132.64 +/- 3.60, and 88.54
      +/- 11.52 for the coating tablet granules containing 10%, 20%, and 30% gelatin in
      HPMC K15M, respectively. The composition of the coating tablet did not affect the
      rate of release of both caffeine and ibuprofen from the coated doughnut-shaped
      tablets. The coatings also adhered to the core tablets for the entire duration of
      the release of the drugs.

PMID- 15265519
TI  - A Raman spectroscopic study of the diclofenac sodium-beta-cyclodextrin
      interaction.
AB  - The inclusion complex of diclofenac sodium (DCFNa) and beta-cyclodextrin (betaCD)
      was prepared and analyzed by using Raman and SERS spectroscopy. The interaction
      between DCFNa and betaCD molecules was evidenced by monitoring the change in the
      peak positions and the widths of some guest molecule bands relative to those
      observed in the spectra of the free compound and 1:1 DCFNa-betaCD physical
      mixture. Raman data have shown that the interaction between the guest and host
      molecules in the 1:1 DCFNa-betaCD complex is maintained both through the
      dichlorophenyl ring and the phenylacetate group. SER spectra revealed that
      depending on the pH value of the solution different isomeric forms of the 1:1
      guest-host complex are preferentially adsorbed on the silver surface via the
      nonbonding electrons of the oxygen atom. The orientation of the adsorbed species
      with respect to the metal surface was also elucidated.

PMID- 15265520
TI  - TGF-beta-induced SMAD signaling and gene regulation: consequences for
      extracellular matrix remodeling and wound healing.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily are
      pleiotropic cytokines that have the ability to regulate numerous cell functions,
      including proliferation, differentiation, apoptosis, epithelial-mesenchymal
      transition, and production of extracellular matrix, allowing them to play an
      important role during embryonic development and for maintenance of tissue
      homeostasis. Three TGF-beta isoforms have been identified in mammals. They
      propagate their signal via a signal transduction network involving receptor
      serine/threonine kinases at the cell surface and their substrates, the SMAD
      proteins. Upon phosphorylation and oligomerization, the latter move into the
      nucleus to regulate transcription of target genes. This review will summarize
      recent advances in the understanding of the mechanisms underlying SMAD modulation
      of extracellular matrix gene expression in the context of wound healing and
      tissue fibrosis.

PMID- 15265521
TI  - Psoriatic architecture constructed by epidermal remodeling.
AB  - Epidermal remodeling is the concept that epidermal architecture is determined by
      a simple self-organizing mechanism; epidermal hyperproliferation constructs
      typical psoriatic architecture. This is based on the assumption that the
      enlargements in both the two-dimensional proliferative compartment (basal cell
      layer) and three-dimensional whole epidermal volume coexist. During this process,
      the dermal papillae become markedly, but passively, expanded by enlargement of
      the proliferative compartment. This creates a considerable shrinkage force
      against the crowded basal cell layer, which is forced to lose adherence to the
      dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis
      characterized by cell detachment, and, consequently, a markedly diminished
      epidermal turnover time in psoriasis. The papillary shrinkage force also explains
      the fact that dermal papillary height does not exceed a certain limit. At the
      cessation of hyperproliferation a normalisation remodeling takes place toward
      normal tissue architecture. Thus the concept of epidermal remodeling explains the
      self-organizing mechanism of the architectural change in psoriasis, which is
      essentially a reversible disorder depending on epidermal hyperproliferation.

PMID- 15265522
TI  - Scrapie transmission following exposure through the skin is dependent on
      follicular dendritic cells in lymphoid tissues.
AB  - BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are chronic
      infectious neurodegenerative diseases that are characterized by the accumulation
      in affected tissues of PrP(Sc), an abnormal isoform of the host prion protein
      (PrP(c)). Following peripheral exposure, PrP(Sc) usually accumulates on
      follicular dendritic cells (FDCS) in lymphoid tissues before neuroinvasion.
      Studies in mice have shown that TSE exposure through scarified skin is an
      effective means of transmission. Following inoculation via the skin, a functional
      immune system is critical for the transmission of scrapie to the brain as severe
      combined immunodeficiency (SCID) mice are refractory to infection. Until now, it
      was not known which components of the immune system are required for efficient
      scrapie neuroinvasion following skin scarification. OBJECTIVE: To determine which
      cells are critical for the transmission of scrapie to the brain following
      inoculation via the skin. METHODS: A chimeric mouse model was used, which had a
      mismatch in PrP(c) expression between FDCs and other bone marrow-derived cells
      within lymphoid tissues. These chimeric mice were challenged with scrapie by skin
      scarification to allow the separate roles of FDCs and lymphocytes in peripheral
      scrapie pathogenesis to be determined. RESULTS: We show that mature FDCs are
      essential for the accumulation of scrapie within lymphoid tissues and the
      subsequent transmission of infection to the brain following TSE exposure by this
      route. Furthermore, we show that the accumulation of PrP(Sc) and infectivity in
      the spleen is independent of PrP expression by lymphocytes or other bone marrow
      derived cells. CONCLUSION: Following inoculation with scrapie by skin
      scarification, replication in the spleen and subsequent neuroinvasion is
      critically dependent upon mature FDCs.

PMID- 15265523
TI  - Cellular senescence induced loss of stem cell proportion in the skin in vitro.
AB  - BACKGROUND: It is known that cellular senescence could affect culture results. A
      previous study on K19 found that the loss of stem cell proportion is the reason
      for difficulties experienced when culturing aged keratinocytes. But the situation
      is unclear, because K19 is not generally accepted as an epidermal stem cell
      marker. OBJECTIVE: The aim of this study was to investigate the effects of
      cellular senescence caused by chronological aging or by repeated subcultures.
      METHODS: The effects of cellular senescence were investigated using monolayer
      cultures of keratinocytes and reconstructed epidermis. We prepared keratinocytes
      from donors of different ages and by repeated subcultures. Flow cytometric
      analysis was performed using alpha6 integrin and CD71 antibodies, and candidate
      keratinocyte stem cell proportions were separated according to reactivities to
      these antibodies. Living skin equivalents (LSEs) were reconstructed using
      keratinocytes from child, adult and elderly donors. RESULTS: Flow cytometric
      analysis showed a decrease in the candidate stem cell proportion in an age- or
      culture passage-dependent manner. LSE experiments showed that a reconstructed
      epidermis using child's keratinocytes was well formed compared to epidermis
      reconstructed using an elderly donor's keratinocytes. Different expression of
      proliferation markers was also observed according to donor age. CONCLUSION: Our
      results showed that cellular senescence by chronological aging or repeated sub
      culture induced the loss of candidate stem cell proportion in keratinocyte
      cultures. This seems to be the reason why it is difficult to culture
      keratinocytes from the elderly or by repeatedly culturing keratinocytes in vitro.

PMID- 15265524
TI  - Objective interpretation of severity of SLS induced edema by stereoimaging.
AB  - BACKGROUND: In the evaluation of the severity of skin inflammations, visual
      scoring system is widely being used as a subjective method. However, it is well
      known that interobserver variations occur even between the interpretations of
      experienced dermatologists. OBJECTIVE: To develop a new objective and
      quantitative method for the evaluation of skin surface contours and for the
      assessment of severity in SLS-induced edema, a new investigatory tool based on
      the concept of "stereoimaging" was studied. Differences between binocular images
      were used by a stereoimage optical topometer (SOT) system capable of calculating
      skin surface topographic information, which was then used to produce a three
      dimensional image. METHODS: We compared the results obtained by SOT with a visual
      scoring system after applying sodium lauryl sulfate (SLS) to skin. The degree of
      edema was assessed qualitatively by visual scoring (0: none, 1: mild edema, 2:
      moderate edema, 3: severe edema). To quantify the severity, five three
      dimensional parameters (S(a), S(z), SL, SA and SV) were used in the SOT analysis.
      RESULTS: The means of these five parameters increased significantly in visual
      grade 1+ compared to visual grade 0 and the means of the five parameters
      decreased significantly and proportionally as the visual grades increased from 1+
      to 3+. A highly significant correlation was found to exist between the visual
      scoring results and the five SOT parameters. CONCLUSION: SOT can be used to
      evaluate the severity of SLS-induced edema objectively and can be extensively
      applied to evaluate the degree of severity in other inflammatory skin conditions.

PMID- 15265525
TI  - Conformational epitope mapping of antibodies against desmoglein 3 in experimental
      murine pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a blistering skin disease caused by IgG
      autoantibodies against desmoglein 3 (Dsg3). We have recently developed an active
      disease mouse model for PV by adoptive transfer of splenocytes from immunized or
      naive Dsg3-/- mice into Rag2-/- recipient mice. OBJECTIVE: In this study, we
      characterized the conformational epitopes of anti-Dsg3 IgG antibodies and their
      pathogenic activities in the PV model mice. METHODS: The binding regions of anti
      Dsg3 IgG antibodies were assessed by competition ELISAs with domain-swapped mouse
      Dsg1/Dsg3 molecules in PV model mice receiving immunized (n = 53) or naive (n =
      56) splenocytes. To compare the pathogenic activity of antibodies against N
      terminal versus C-terminal extracellular domains, Dsg3-/- mice were immunized
      with the residues 1-162 or the residues 403-565 of mouse Dsg3, and the
      splenocytes were adoptively transferred into Rag2-/- mice. RESULTS: The middle to
      C-terminal extracellular domains of Dsg3 (residues 195-565) showed >50%
      competition in 51/53 (96.2%) and 45/56 (80.4%) while the N-terminal domain
      (residues 1-162) showed >50% competition only in 3/53 (5.7%) and 8/56 (14.3%) in
      mice receiving immunized and naive splenocytes, respectively. The mice receiving
      Dsg3-/- splenocytes immunized with the residues 403-565 developed the PV
      phenotype as early as and as severely as the mice receiving splenocytes immunized
      with the residues 1-162. CONCLUSIONS: In PV model mice the antibodies were
      dominantly raised against the middle to C-terminal extracellular domains of mouse
      Dsg3 where amino acid sequences are less conserved among desmoglein isoforms and
      that those antibodies may also be involved in the blister formation.

PMID- 15265526
TI  - Persistence of Staphylococcus aureus colonization on the skin of NC/Nga mice.
AB  - BACKGROUND: Colonization of Staphylococcus aureus (S. aureus) on skin is one
      factor which can worsen atopic dermatitis (AD). The reduction of bacterial
      colonization in these lesions was reported to be effective for the treatment of
      subjects with AD. NC/Nga mice are recognized to be a model of AD. OBJECTIVE: We
      examined the susceptibility of S. aureus colonization on the skin in NC/Nga mice,
      as compared with findings in BALB/c mice. METHODS: The number of S. aureus on the
      skin was counted and serum corticosterone, serum interferon-gamma (IFN-gamma) and
      interleukin (IL)-12 levels were measured. The effects of dexamethasone on number
      of S. aureus on the skin and serum IFN-gamma and interleukin IL-12 levels were
      also examined. RESULTS: The number of S. aureus increased in parallel with the
      severity of the dermatitis in these mice, and the remaining number of S. aureus
      on the skin after topical treatment of S. aureus suspension was higher than that
      in BALB/c mice. Serum IFN-gamma and IL-12 concentrations in NC/Nga mice were
      lower than in BALB/c mice, and the circadian variations of serum corticosterone
      concentrations in NC/Nga mice tended to reveal higher levels compared with the
      circadian variations in BALB/c mice. Continuous administration of dexamethasone
      inhibited the elimination of S. aureus from skin surfaces of BALB/c mice. Serum
      IFN-gamma and IL-12 concentrations in dexamethasone-treated BALB/c mice were
      lower than those in vehicle-treated BALB/c mice. CONCLUSION: Our data support the
      notion that high levels of circadian variations of endogenous glucocorticoid lead
      to a lack of protection against bacteria and a persistence of S. aureus
      colonization on the skin in NC/Nga mice.

PMID- 15265527
TI  - Rapid diagnosis of lipoid proteinosis using an anti-extracellular matrix protein
      1 (ECM1) antibody.

PMID- 15265528
TI  - Remodeling of desmosomal and hemidesmosomal adhesion systems during human hair
      follicle development.

PMID- 15265529
TI  - Effects of phenol peeling on dermal endothelial cells.

PMID- 15265530
TI  - Association of the Arg16Gly polymorphism of the beta-2-adrenergic receptor with
      psoriasis.

PMID- 15265531
TI  - Association of HLA class I alleles with vitiligo in Chinese Hans.

PMID- 15265532
TI  - The influence of systemic inflammation on inflammation in the brain: implications
      for chronic neurodegenerative disease.
AB  - Systemic inflammation is associated with sickness behaviour and signals pass from
      the blood to the brain via macrophage populations associated with the brain, the
      perivascular macrophages and the microglia. The amplitude, or gain, of this
      transduction process is critically dependent on the state of activation of these
      macrophages. In chronic neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease, or prion disease the pathology is associated with a highly
      atypical inflammatory response, characterised by the activation of the macrophage
      populations in the brain: the cells are primed. Recent evidence suggests that
      systemic inflammation may impact on local inflammation in the diseased brain
      leading to exaggerated synthesis of inflammatory cytokines and other mediators in
      the brain, which may in turn influence behaviour. These interactions suggest that
      systemic infections, or indeed any systemic challenge that promotes a systemic
      inflammatory response, may contribute to the outcome or progression of chronic
      neurodegenerative disease.

PMID- 15265533
TI  - Of mice and men, corticosteroids, and vicarious participation.

PMID- 15265534
TI  - Physical defeat reduces the sensitivity of murine splenocytes to the suppressive
      effects of corticosterone.
AB  - Social disruption (SDR) in male mice reduces the sensitivity of their splenocytes
      to the actions of glucocorticoids. To determine whether physical defeat is
      necessary for the development of this reduced sensitivity, a modification of the
      SDR paradigm was employed in which mice were exposed to fighting conspecifics in
      the presence or absence of physical contact. This was accomplished by dividing a
      cage of 5 resident male C57BL/6 mice in half with a wire mesh partition so that 2
      of the mice in the cage (SDR Physical Contact mice) fought and were defeated by
      an aggressive male C57BL/6 intruder that was placed into the cage for 2h for up
      to 6 days, while the remaining 3 resident mice (SDR Sensory Contact mice) were on
      the opposite side of the partition and thus prevented from physically interacting
      with the intruder. Although both the SDR Physical Contact and the SDR Sensory
      Contact mice had significantly elevated corticosterone levels and displayed
      submissive postures toward the intruder, only the SDR Physical Contact animals
      developed functional glucocorticoid resistance. The viability of LPS-stimulated
      splenocytes cultured from the SDR Physical Contact mice was not affected by
      pharmacological doses of corticosterone, whereas splenocyte viability was
      significantly reduced by corticosterone in cultured cells from SDR Sensory
      Contact and control mice. This study indicates that exposure to a stressful
      environment in the absence of physical attack does not reduce the sensitivity of
      murine splenocytes to the suppressive effects of corticosterone.

PMID- 15265535
TI  - Exogenous pyruvate prevents stress-evoked suppression of mitogen-stimulated
      proliferation.
AB  - Although the phenomenon that psychological stress influences disease onset and
      progression is well established, the mechanisms underlying stress-evoked
      compromise of immune function remain unspecified. To test the hypothesis that
      energetic shortages compromise immunity, we evaluated the effectiveness of
      pyruvate, a metabolic supplement, to prevent stress-evoked suppression of mitogen
      stimulated splenocyte proliferation. Male C57BL/6 mice were subjected to 2h of
      restraint once daily for 14 days. Consistent with previous studies, mitogen
      stimulated splenocyte proliferation was reduced after restraint; in contrast,
      mice that received pyruvate injections immediately following each episode of
      restraint did not reduce splenocyte proliferation. In addition, restraint-evoked
      corticosterone elevation did not habituate in animals treated with pyruvate,
      suggesting that glucocorticoids are not exclusively immunosuppressive. The ratio
      of pyruvate to lactate, an index of aerobic metabolism, was elevated in mice
      exposed to restraint suggesting that mice exposed to restraint were
      preferentially using aerobic metabolism and producing more ATP per unit of
      pyruvate than non-restrained mice. Furthermore, two of the effective doses of
      pyruvate (0.5 and 500.0mg/kg) altered glucose levels suggesting a metabolic
      function of the supplement. Although several different mechanisms could possibly
      mediate the changes in splenocyte proliferation, these results support the
      hypothesis that stress-evoked immunosuppression may be a function of metabolic
      energy shortages and can be prevented via pyruvate supplementation.

PMID- 15265536
TI  - Permeability of the mouse blood-brain barrier to murine interleukin-2:
      predominance of a saturable efflux system.
AB  - Interleukin (IL)-2, a T helper (TH)1 cell-derived glycoprotein with potent
      neuromodulatory effects, is implicated in the etiology and pathogenesis of
      various psychiatric and neurological disorders. Paralleling these findings,
      chronic IL-2 intravenous immunotherapy may induce similar psychopathological
      outcomes. The findings that acute or repeated injections of IL-2 induce motor and
      cognitive abnormalities in rodents are consistent with these clinical findings,
      and raise the possibility that IL-2 crosses the blood-brain barrier (BBB) to
      alter brain function. However, little is known about the ability of IL-2 to enter
      the brain or whether its effects vary with the chronicity of IL-2 treatment.
      Here, we found that radioactively labeled mouse IL-2 (I-IL-2) given intravenously
      entered the brain at a low rate (Ki=0.142+/-0.044microl/g-min) by a non-saturable
      process. Repeated injections of either IL-2 or vehicle altered the kinetics of
      entry without producing a net effect on IL-2 entry. When I-IL-2 was given by
      brain perfusion, the entry rate greatly increased over 10-fold to 2.2+/
      0.805microl/g-min. This suggests a circulating factor is retarding the entry of
      IL-2 into the brain. A paradoxic increase in the rate of I-IL-2 entry into brain
      occurred when an excess of unlabeled IL-2 was included in the brain perfusate,
      suggesting a saturable CNS-to-blood efflux system. Intracerebroventricular
      injection of I-IL-2 with and without unlabeled IL-2 confirmed the presence of a
      saturable efflux system. We conclude that IL-2 entry into the brain is low
      because of the absence of a blood-to-brain transporter and further retarded by
      circulating factors and a CNS-to-blood efflux system. This is the first
      description of a saturable CNS-to-blood efflux system for a cytokine. We
      postulate that this efflux system may protect the brain from circulating IL-2.

PMID- 15265537
TI  - Changes in neutrophil functions in astronauts.
AB  - Exploration class human spaceflight missions will require astronauts with robust
      immune systems. Innate immunity will be an essential element for the healthcare
      maintenance of astronauts during these lengthy expeditions. This study
      investigated neutrophil phagocytosis, oxidative burst, and degranulation of 25
      astronauts after four space shuttle missions and in nine healthy control
      subjects. Space flight duration ranged from 5 to 11 days. Blood specimens were
      obtained 10 days before launch, immediately after landing, and 3 days after
      landing. The number of neutrophils increased by 85% at landing compared to
      preflight levels. The mean values for phagocytosis of Escherichia coli and
      oxidative burst capacity in neutrophils from astronauts on the 5-day mission were
      not significantly different from those observed in neutrophils from the control
      subjects. Before and after 9- to 11-day missions, however, phagocytosis and
      oxidative burst capacities were significantly lower than control mean values. No
      consistent changes in degranulation or expression of surface markers were
      observed before or after any of the space missions. This study indicates that
      neutrophil phagocytic and oxidative functions are affected by factors associated
      with space flight and this relationship may depend on mission duration.

PMID- 15265538
TI  - ProCRH in the teleost Ameiurus nebulosus: gene cloning and role in LPS-induced
      stress response.
AB  - The procorticotrophin-releasing hormone (proCRH) gene from the teleost Ameiurus
      nebulosus was cloned by direct and inverse PCR-based technologies and
      characterized. The structure of the proCRH gene shows the presence of four exons
      and three introns giving a total length of 1416bp. Sequence similarity with the
      corresponding proCRH coding sequences in Tilapia mossambica and Homo sapiens is
      97.7 and 78%, respectively. Western blot experiments performed with an anti-human
      CRH (1-41) antibody revealed the presence of an immunoreactive molecule with an
      approximate MW of 18kDa, a value comparable to that of the putative catfish
      proCRH peptide. These data suggest that proCRH could be active in A. nebulosus
      without any cleavage. ProCRH immunoreactive molecules were found in the central
      nervous system (CNS) and were immunocytochemically detected in the head kidney
      and in the pancreatic gland. Western blot and immunocytochemical experiments
      showed an increase in proCRH expression in the CNS after 15min but not after
      120min exposure to LPS. In contrast, the increased immunopositivity was
      detectable in the pancreas only after 120min of treatment, but in the head kidney
      throughout the entire period of exposure. Our findings indicate that the CNS
      responds to the altered conditions for a shorter period of time than the
      peripheral organs, suggesting a hierarchical and time-regulated stress response.
      However, an independent response in the peripheral organs cannot be excluded in
      this scenario.

PMID- 15265539
TI  - Acute stress effects on local Il-1beta responses to pathogens in a human in vivo
      model.
AB  - The combined effects of stress and antigen on interleukin-1beta (Il-1beta) have
      rarely been studied locally at the site of microbial challenges in vivo, so far.
      We here propose a model for the analysis of such effects in humans and examine
      its utility for acute stress trials. Twelve students (6 male, 6 female) refrained
      from oral hygiene in two antagonistic quadrants for 28 days to allow for
      increasing bacterial stimulation of the respective gingival sites due to
      accumulation of microbial plaque. Good oral hygiene was maintained in the
      remaining quadrants. At day 27 and 28 students were subjected to either stress
      ('public speech') or a control condition, in a cross-over design. Samples of
      gingival crevicular fluid (GCF) which emerges between the tooth surface and the
      gingival epithelium as transudate of healthy and exudate of inflamed gingival
      tissue, were taken immediately after stress and 60 min later for Il-1beta
      analysis. Salivary cortisol was assessed to prove the validity of the stress
      protocol. Stress induced a profound increase of salivary cortisol (p=.001).
      Repeated measures (stress x time x hygiene) ANOVA with gender as between factor
      revealed significant stress (p=.014) and hygiene (p=.038) effects on GCF-Il-1beta
      concentrations and tentatively significant hygiene x time (p = .097) and stress x
      time x hygiene x gender (p=.107) interactions. Stress induced an increase of Il
      1beta as did plaque accumulation. The merits of the proposed model are discussed.
      It is concluded that it is well suited for the assessment of the effects of
      stress on inflammatory responses in vivo in humans.

PMID- 15265540
TI  - The rank assessed in a food competition test influences subsequent reactivity to
      immune and social challenges in mice.
AB  - The purpose of this study was to investigate whether, in a stable social
      environment, social interactions are responsible for individual, endocrine and
      immune differences among group members. Cage-mates were classified according to
      their rank in a food competition test. The influence of the rank was evaluated in
      two different situations activating neuroendocrine and immune systems. A first
      experiment used a context of repeated social stress. A second experiment
      investigated the influence of rank on the response to a bacterial infection by
      BCG. Endocrine and immune functions were assessed by measuring plasma
      corticosterone levels, splenocyte proliferation and in vitro cytokine production.
      In control undisturbed groups, plasma levels of corticosterone were lower in low
      ranking (LR) mice than in intermediate (IR) and high ranking (HR) mice. LPS
      induced splenocyte proliferation and in vitro cytokine production were
      independent of rank. In response to social stress, corticosterone increased
      similarly in all categories but the increase in splenocyte proliferation was more
      pronounced in HR animals. During BCG infection, the rank influenced the
      production of IL-10 and IFN-gamma by tuberculin-stimulated splenocytes during the
      acute phase of the infection but not after 94 days of infection. Cytokine
      production in response to LPS and bacterial growth were not affected by the rank.
      Therefore, social interactions emerging in a stable social group may be involved
      in the individual differences observed in endocrine activity and in immune system
      reactivity.

PMID- 15265541
TI  - The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor
      necrosis factor-alpha production.
AB  - Septic shock is believed to be a consequence of excessive stimulation of the
      immune system by bacterial toxins that results in systemic overproduction of
      proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), IL
      1, and IL-6. Various studies have shown that TNF-alpha, a major mediator of
      septic shock, induces tissue injury, loss of blood pressure, organ failure, and
      ultimately death. Administration of the opioid antagonist naloxone has been
      reported to reverse opiate-mediated hypotension, promote organ perfusion and
      increase patient survival. In this study, we examined the mechanism by which the
      opioid receptor antagonist, naltrexone, modulates the septic shock response in
      BALB/c mice after injection with lipopolysaccharide (LPS) or staphylococcal
      enterotoxin B (SEB) in combination with d-galactosamine (d-gal), or with
      agonistic anti-Fas antibody (Jo2) alone. Each of these treatments induced rapid
      onset, acute shock, and ultimately mortality (6-9h after injection), although
      different mechanisms are involved. Administration of the opioid antagonist
      naltrexone protected mice from shock induced by LPS+d-gal, but not SEB+d-gal or
      Jo2 antibody, a protective effect that was reversed by morphine. Naltrexone
      significantly inhibited the production of TNF-alpha induced by LPS, but not SEB
      in vivo. When bone marrow-derived, splenic or peritoneal macrophages were treated
      with LPS in vitro, administration of naltrexone had no direct effect on TNF-alpha
      production. These results suggest that naltrexone is capable of preventing LPS
      induced septic shock mortality by indirect inhibition of TNF-alpha production in
      vivo.

PMID- 15265542
TI  - Freeze drying--principles and practice for successful scale-up to manufacturing.
AB  - Freeze Drying involves transfer of heat and mass to and from the product under
      preparation, respectively, thus it is necessary to scale these transport
      phenomena appropriately from pilot plant to manufacturing-scale units to maintain
      product quality attributes. In this manuscript we describe the principal approach
      and tools utilized to successfully transfer the lyophilization process of a
      labile pharmaceutical product from pilot plant to manufacturing. Based on pilot
      plant data, the lyophilization cycle was tested during limited scale-up trials in
      manufacturing to identify parameter set-point values and test process parameter
      ranges. The limited data from manufacturing were then used in a single-vial
      mathematical model to determine manufacturing lyophilizer heat transfer
      coefficients, and subsequently evaluate the cycle robustness at scale-up
      operating conditions. The lyophilization cycle was then successfully demonstrated
      at target parameter set-point values.

PMID- 15265543
TI  - Crystal structure and surface properties of an investigational drug--a case
      study.
AB  - In this study we investigate the correlations between the single crystal
      structure, the crystal habitat and morphology, and surface energetics of an
      investigational pharmaceutical compound. Crystal structure of this
      investigational pharmaceutical solid has been solved from single crystal X-ray
      analysis. Crystallographic data are as follows: triclinic, P1 (no. 1), a = 6.1511
      (8) A, b = 13.5004 (18) A, c = 17.417 (2) A, alpha = 68.259 (2) degrees, beta =
      80.188 (2) degrees, gamma = 82.472 (2) degrees, V = 1320.2 (3) A(3), Z = 2. The
      external morphology of this crystalline solid was predicted by molecular
      modelling using attachment energies to be thin-plate like with a dominant face
      (001). The predicted morphology was confirmed by scanning electron micrographs
      (SEM) and the Miller Index of the dominant face was complemented by X-ray powder
      diffraction (XRPD) method. The microscopic layering structures of crystals and
      surface stability of the dominant faces were investigated using atomic force
      microscopy (AFM). Contact angle measurement showed that the surface of the
      dominant face is hydrophilic as predicted from crystal structure.

PMID- 15265544
TI  - Measurement of the flow properties of powders with special reference to die fill.
AB  - The flow behaviour of four pharmaceutical powders was investigated using a model
      shoe-die-filling system. The variation of mass delivered to the die as a function
      of shoe velocity provides a measure of flowability. The paper discusses the
      concept of critical velocity, above which incomplete filling is observed, in the
      context of pharmaceutical powders. The filling process was recorded using a high
      speed video system, which allowed the different flow patterns to be observed, and
      how this influences the critical velocity to be evaluated. The influence of
      humidity, which was investigated in detail for one of the powders, was found to
      be small. The initial conditioning of the material, the die opening and if die
      filling takes place in air or in vacuum, however, were found to change the flow
      behaviour significantly.

PMID- 15265545
TI  - Uniformity and physical states of troglitazone in solid dispersions determined by
      electron probe microanalysis and microthermal analysis.
AB  - Solid dispersions of troglitazone with PVP K30 in a weight ratio of 1:2 were
      prepared by the closed melting method. Solid dispersions that exhibit different
      degrees of crystallinity (0 and 36%) were prepared by changing the charged amount
      of water, which functions as a plasticizer for PVP K30. Electron probe
      microanalysis (EPMA) and microthermal analysis (micro TA) of the solid
      dispersions were performed to investigate the uniformity and physical state of
      troglitazone in the solid dispersions. The EPMA study confirmed that troglitazone
      was dispersed homogeneously in the sample whose apparent crystallinity was 0%.
      However, the sample with a 36% crystallinity was heterogeneous. The micro TA
      study showed that the sample with a 36% crystallinity was present in two states,
      crystal and amorphous. EPMA and micro TA would be useful tools to confirm the
      uniformity and physical states, respectively, of solid dispersions.

PMID- 15265546
TI  - Membrane permeability related physicochemical properties of a novel gamma
      secretase inhibitor.
AB  - Pharmaceutical profiling studies were conducted on a novel prototype gamma
      secretase inhibitor, to determine the potential of its oral absorption. Such
      compounds can be of use in the treatment of Alzheimer's disease (AD). The studies
      included determination of solubility, dissociation constant (pK(a)),
      octanol/water partition coefficient (log P) and the capacity factor (k'(IAM)) on
      immobilized artificial membrane (IAM) chromatographic columns. The compound is
      very slightly solubility in water (120 +/- 50 microg/mL) but the solubility
      increased considerably in basic medium (270 +/- 60 microg/mL). The compound
      exhibited pK(a) of (10.36 +/- 0.11); and log P of (3.36 +/- 0.16) determined by
      shake-flask method and (3.31 +/- 0.01) determined by high performance liquid
      chromatography (HPLC). The experimentally determined log P values correlated well
      with the calculated one of 3.44. The observed log k'(IAM) value of (2.79 +/-
      0.04) indicates that the compound can reasonably be expected to have high
      membrane permeability, and therefore, good absorption profile if taken orally.
      This conclusion is also supported by other parameters determined.

PMID- 15265547
TI  - Formulation and characterization of bupivacaine lipospheres.
AB  - Bupivacaine lipospheres were prepared as a parenteral sustained-release system
      for post-operative pain management. Bupivacaine free base was incorporated into
      micron-sized triglyceride solid particles coated with phospholipids, which were
      formed via a hot emulsification and cold resolidification process. The
      bupivacaine liposphere dispersions were characterized with respect to drug
      loading, particle-size distribution, and morphology. Gelation of the fluid
      liposphere dispersions was observed at different time intervals upon storage. The
      type of phospholipids used in the formulation was found to have a major impact on
      the gelation of the dispersion. The use of synthetic phospholipids instead of the
      natural phospholipids in the formulation yielded bupivacaine liposphere
      dispersions exhibiting prolonged gelation time. The addition of a hydrophilic
      cellulosic polymer can further improve the physical stability of the dispersion.

PMID- 15265548
TI  - Changes in surface properties by granulation and physicochemical stability of
      granulated amorphous cefditoren pivoxil with additives.
AB  - The evaluation of the physicochemical stability of granules of amorphous
      cefditoren pivoxil (CDTR-PI), alone or with polymers, demonstrated that
      granulated amorphous CDTR-PI with hydroxypropyl methylcellulose was the most
      stable. We measured glass transition temperature by differential scanning
      calorimetry (DSC). The molecular mobility of the whole granules did not change,
      and it was not consistent with the results of the evaluation of physicochemical
      stability. Peak shifts were observed in IR spectra of amorphous CDTR-PI with
      polymers after granulation, and the shifts were similar to those observed for
      spray-dried samples. Furthermore, the shifts were not observed after the granules
      were ground. Acid-base parameters, which were also measured by inverse gas
      chromatography (IGC), changed after granulation. These results suggested that on
      the surface of the granules, CDTR-PI and the polymers would be mixed
      monomolecularly, as in the spray-dried samples. The changes in the molecular
      state of a drug when mixed monomolecularly with a polymer on the surface of
      granules were successfully confirmed by IGC and IR.

PMID- 15265549
TI  - Interparticle van der Waals force in powder flowability and compactibility.
AB  - Particle flowability and compactibility are the two critical process parameters
      tested when a pharmaceutical material is formulated for a tabletting process.
      These behavioral descriptions are strongly affected by geometrical, physical,
      chemical and mechanical particle properties, as well as operational conditions.
      The property influences are broadly known in a qualitative sense, but have
      largely escaped fundamental quantitative description. Various measurement methods
      have been separately developed for each of these properties which provide
      comparative indices to assist in process and formulation design. This paper seeks
      to establish the connections between interparticle van der Waals force and both
      flowability and compactibility, and therefore also the inter-relations between
      the two apparently distinct properties. Paracetamol and the excipients often
      associated with it for tabletting are used as test materials to provide an
      initial validation of the theoretical development. These powders are well
      characterized and known to be particularly difficult with respect to flowability
      and compactibility.

PMID- 15265550
TI  - Beta-cyclodextrin as a suitable solubilizing agent for in situ absorption study
      of poorly water-soluble drugs.
AB  - To evaluate the intestinal permeability of poorly water-soluble compounds, it is
      of importance to completely dissolve them in a medium and to avoid precipitation
      during experiments. This study was undertaken to find an agent possessing a high
      solubilizing capacity and exhibiting minimal modulating impact on membrane
      integrity and absorption systems such as passive diffusion and carrier-mediated
      permeation. Phenytoin dissolution was compared in the presence of seven
      solubilizing agents at concentrations of 1, 2, or 5% using a centrifugation
      method. The capacity to dissolve phenytoin was great in beta-cyclodextrin (beta
      CD) and hydroxypropyl beta-cyclodextrin, followed by Tween 80. Those of methanol,
      dimethyl sulfoxide, dimethyl acetoamide, and polyethylene glycol 400 were much
      lower than expected. One percent beta-CD did not alter the absorption of
      fluorescein isothiocyanate-dextran 4,000 or the release of protein and lactate
      dehydrogenase into in situ loop contents, suggesting that 1% beta-CD had no
      significant impact on the integrity of the intestinal membrane. One percent beta
      CD also did not alter the absorption of caffeine, ceftibuten, or rhodamine 123
      from in situ jejunal loops, indicating no interference with passive diffusion and
      active transports mediated by a peptide transporter and P-glycoprotein. In
      conclusion, 1% beta-CD is a suitable solubilizing agent for evaluating in situ
      intestinal absorption of poorly water-soluble compounds.

PMID- 15265551
TI  - Time-release compression-coated core tablet containing nifedipine for
      chronopharmacotherapy.
AB  - Compression-coated time-release tablets (CC tablets) containing nifedipine,
      dihydropyridine Ca channel blocker, in the core tablet were prepared by dry
      coating with different polyethylene oxide-polyethylene glycol mixtures. Each
      formulation showed a clear lag period before nifedipine release initiation,
      followed by sustained drug release lasting up to 24 h. The lag time of nifedipine
      release increased as the amount of polyethylene oxide in the outer layer
      increased. To investigate the applicability of such CC-tablets for
      chronopharmacotherapy, the pharmacokinetics of CC-1 and CC-2 tablets, with
      different in vitro lag times before drug release, were compared with the
      pharmacokinetics of a sustained-release (SR) tablet in dogs. The times of first
      nifedipine appearance (TFA) in plasma were 0.7 +/- 0.3 h for SR, 2.5 +/- 1.2 h
      for CC-1, and 5.3 +/- 1.0 h for CC-2. These data show a significant difference in
      in vivo lag time (P < 0.01) among the three formulations that correlates with the
      in vitro lag times. Thus, the in vivo lag time could be predicted from the in
      vitro lag time. Additionally, higher plasma nifedipine concentrations were
      observed at 8 h after administration of the CC-2 than that observed for the SR
      tablet. These results indicate that a CC-tablet with a lag time before drug
      release is a potentially useful formulation for chronopharmacotherapy that can
      control the time and duration of plasma drug concentration better than existing
      SR technologies.

PMID- 15265552
TI  - Topical delivery of retinyl ascorbate co-drug. 1. Synthesis, penetration into and
      permeation across human skin.
AB  - A novel synthetic technique was used to synthesise the co-drug retinyl ascorbate
      (RA-AsA) ester from all-trans-retinyl chloride (RA) and L-ascorbic acid (AsA)
      suspended in ethanol at low temperature. Its log P, solubility in a Me:PBS, 50/50
      at pH 4.8 and degradation constant were determined. The flux and permeation
      coefficient were determined using heat separated human skin membrane, and skin
      penetration was determined by tape stripping using full thickness human. All
      experiments were performed in parallel with retinyl palmitate (Rol-Pal) and
      ascorbyl palmitate (AsA-Pal), which are used in commercial topical formulations.
      RA-AsA exhibited favourable log P (2.2), with stability much greater than RA and
      AsA, but similar stability to Rol-Pal and AsA-Pal. The flux of RA-AsA was lower
      than for Rol-Pal and AsA-Pal. RA-AsA also demonstrated higher skin retention than
      the other two esters, but delivered more RA and AsA to the viable epidermis than
      retinol from Rol-Pal and ascorbic acid from AsA-Pal. Overall, the data suggest
      the potential value of RA-AsA co-drug for the purpose of treating damage to skin
      resulting from UV-induced production of free radicals.

PMID- 15265553
TI  - Evaluation of the clearance characteristics of various microspheres in the human
      nose by gamma-scintigraphy.
AB  - The nasal cavity possesses many advantages as a site for drug delivery, such as;
      ease of administration, applicability for long-term treatments and a large
      surface area for absorption. One important limiting factor for nasal drug
      delivery is the limited time available for absorption within the nasal cavity due
      to mucociliary clearance. Several drug delivery systems including different kinds
      of microspheres have been tried for encapsulation of drugs and increasing the
      residence time in nasal cavity. In this study the clearance rate of three kinds
      of microspheres (Alginate, PLGA, and Sephadex) was determined by gamma
      scintigraphy with lactose powder being used as negative control. (99m)Tc labeled
      microspheres were prepared using technetium pertechnetate in the presence of a
      potent reducing agent, stannus chloride. The labeling procedure was set in a
      manner that each 3-5 mg of microspheres contained 2 MBq of radioactivity.
      Labeling efficiency was calculated by paper chromatography using acetone as a
      mobile phase. Each delivery system containing 2 MBq of activity was administered
      into right nostril of four healthy volunteers and 1 min static views were
      repeated each half an hour until 4 h. Clearance rates were compared using two
      regions of interest (ROIs); the initial site of deposition of particles, and all
      of the nasopharynx region. The clearance rate of each one of microspheres was
      calculated after applying the physical decay corrections. The mean labeling
      efficiencies for Alginate, PLGA, and Sephadex microspheres were calculated as
      60%, 59%, and 74%, respectively. The cleared percent of formulations from
      nasopharynx region after 4 h was determined as follows: PLGA microspheres 48.5 +/
      8.2%; Alginate microspheres 45.0 +/- 0.8%; Sephadex microspheres 63.1 +/- 3.4%;
      lactose powder 74.5 +/- 4.9%. Alginate and PLGA microspheres showed the lowest
      clearance rate compared to lactose powder (P < 0.0001 and P < 0.001,
      respectively), followed by Sephadex microspheres (P < 0.01). The clearance
      profiles of formulations from deposition ROI and nasopharynx ROI were identical.
      This study shows that Alginate and PLGA microspheres have the highest
      mucoadhesion properties and are suitable nasal delivery systems. Futhermore, this
      study proves that limiting step for the nasal clearance of nasally administered
      particulate systems is their dislocation from the initial site of deposition, and
      their following interactions with mucus layer in the rest of the nasal passage
      does not significantly affect the clearance time.

PMID- 15265554
TI  - The effects of additives on the growth and morphology of paracetamol
      (acetaminophen) crystals.
AB  - It is well known that the presence of impurities can dramatically affect the
      nucleation, morphology, and chemical properties of crystals. Although literature
      is replete with examples of impurity or additive-induced modifications of
      crystals, few have examined the interaction of these compounds with distinct
      growing faces. In this study, we utilize atomic force microscopy (AFM) and
      scanning electron microscopy (SEM) to investigate the influence of two
      structurally related additives of paracetamol (acetaminophen) on its crystal
      morphology. We also probe, in situ, the effects of these additives on the
      morphology and growth rate of steps on the (0 0 1) face of the crystal. This
      study, in conjunction with further investigations, aims to establish the specific
      mechanisms of inhibition of these additives on each face of paracetamol, and
      provide a means of overcoming the poor compaction behaviour of paracetamol.

PMID- 15265555
TI  - Comparative in vitro-in vivo study of two quinine rectal gel formulations.
AB  - The main objective of this work was to develop and evaluate rectal quinine
      paediatric formulations to treat acute uncomplicated malaria attack in some
      African countries. Developed dosage forms must be able to assure a prolonged
      release in the rectum but not too much so as to avoid product expulsion by the
      child anus. Two quinine rectal gels, namely mucoadhesive (MA) gel and
      thermosensitive (TS) gel, containing 20 mg quinine base/g were developed and
      evaluated in vitro and in vivo in the rabbit. The MA and the TS gels contained
      hydroxypropyl methylcellulose 4000 (HPMC) and poloxamer 407, respectively. The
      calculated in vitro release exponent (n) values suggested that drug was released
      from both gels by non-Fickian diffusion. Both gels exhibit practically similar
      efficient of dissolution (ED%) which was not reflected in the plasma and,
      therefore, quinine bioavailability from MA gel was found to be higher than that
      obtained from TS gel and their AUC(0-infinity) were statistically different (P =
      0.0006). The t(1/2) values of quinine were significantly higher for Hydrogels
      than for IV and rectal solutions. MRT values displayed by TS gel and MA gel were
      not statistically different but were about 3.8- and 1.3-fold, respectively,
      larger than those obtained for IV solution and rectal solution, respectively.
      These results confirm the sustained-release behaviour of both hydrogels in the
      rabbit. Tolerability study of hydrogels didn't show any damage on the rectal
      mucosa of the rabbit.

PMID- 15265556
TI  - Influence of cyclodextrins on in vitro human skin absorption of the sunscreen,
      butyl-methoxydibenzoylmethane.
AB  - The effects of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutylether
      beta-CD (SBE7-beta-CD) on in vitro human skin penetration and retention of the
      sunscreen agent butyl-methoxydibenzoylmethane (BM-DBM) were investigated. The
      interaction between the UV filter and the cyclodextrins was studied in water by
      phase-solubility analysis. Solid complexes were prepared by the co-evaporation
      method and characterized by (1)H NMR spectroscopy, thermal analysis and powder X
      ray diffraction. Solutions containing BM-DBM free or complexed with cyclodextrins
      were applied to excised human skin in Franz diffusion cells and the amount of
      sunscreen permeated after 6 h into the stratum corneum, viable epidermis, dermis
      and receptor fluid was assessed by HPLC. As much as 14.10-16.78% of the applied
      dose of BM-DBM penetrated within the skin tissue. No sunscreen was detected in
      the dermis and in the receiver phase. The greater proportion (84.6-95.5%) of the
      absorbed UV filter was localized in the stratum corneum with no significant
      differences between uncomplexed or complexed BM-DBM. Notable levels (2.29% of the
      applied dose) of the sunscreen agent accumulated in the epidermis from the
      preparation containing free BM-DBM. The epidermal concentration of the UV filter
      was markedly reduced (0.66% of the applied dose) by complexation with SBE7-beta
      CD, whereas HP-beta-CD had no effect. The decreased BM-DBM retention in the
      epidermal region achieved by SBE7-beta-CD limits direct contact of the sunscreen
      and of its reactive photolytic products with the skin viable tissues.

PMID- 15265557
TI  - Antimicrobial activity of polyurethanes coated with antibiotics: a new approach
      to the realization of medical devices exempt from microbial colonization.
AB  - Intravascular devices are widely used for vascular access but are associated with
      substantial risk of development of devices-related bloodstream infection (DR
      BSI), which causes a considerable increase of morbidity and mortality, prolonged
      hospitalisation and growing medical costs. Since conventional treatment of DR-BSI
      fails in a significant number of cases, resulting in removal of the device, new
      approaches are needed to prevent bacterial colonization. In this paper, two
      antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes
      exhibiting acidic or basic properties. The influence of the type of antibiotic
      polymer interaction on the amount of adsorbed antibiotic and on the release
      kinetics was studied. It was seen that the antibiotic-polymer affinity increases
      both with the introduction in the polymer side-chain of functional groups and
      with the matrix hydrophilicity. The antimicrobial activity of the treated
      polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of
      antibiotic adsorbed, on the strength of drug-matrix interaction and on the water
      swelling of the polymers. The inhibition zone of bacterial growth lasts only a
      few hours for the amoxi-coated polymers while remains at least for five months
      for the rifampin-coated ones. The presence of serum proteins decreases by about
      30% the inhibition zone diameter of these latest matrices after two months.

PMID- 15265559
TI  - Photolysis of riboflavin in aqueous solution: a kinetic study.
AB  - The kinetics of photolysis of aqueous riboflavin solutions on UV and visible
      irradiation has been studied in the pH range 1-12 using a specific multicomponent
      spectrophotometric method for the simultaneous determination of riboflavin and
      its major photoproducts (formylmethylflavin, lumichrome and lumiflavin). The
      apparent first-order rate constants for the photodegradation reactions in the pH
      range have been determined. The log k-pH profiles indicate that riboflavin has
      maximum photostability around pH 5-6, at which the rate of oxidation-reduction of
      the molecule is lowest. The cationic and anionic forms of riboflavin are non
      fluorescent and less susceptible to photolysis than the non-ionised molecule as
      indicated by the relatively slow rates below pH 3.0 and above pH 10.0. The rate
      of photolysis is increased up to 80-fold at pH 10.0, compared to that at pH 5.0,
      due to increase in redox potentials with an increase in pH and consequently the
      ease with which the molecule is oxidised. The increase in rate at pH 3.0,
      compared to that at pH 5.0, appears to be due to the involvement of the excited
      singlet state as well as the triplet state in riboflavin degradation. The
      apparent first-order rate constants for the photolysis of riboflavin at pH 5.0
      10.0 with UV and visible radiation are 0.185 x 10(-2) to 13.182 x 10(-2)min(-1)
      and 0.098 x 10(-2) to 7.762 x 10(-2)min(-1), respectively.

PMID- 15265558
TI  - AFM studies of the crystallization and habit modification of an excipient
      material, adipic acid.
AB  - Atomic force microscopy (AFM) has been used to investigate the (1 0 0) face of
      crystalline adipic acid, both in air and liquid environments. In air, surface
      reorganization occurred during scanning of the AFM probe, which has been
      investigated using single point force-distance analysis under a controlled
      relative humidity (RH) environment. We suggest such reorganization can be
      attributed to the influence of a network of water molecules bound to the
      hydrophilic (1 0 0) surface permitting local AFM tip-enhanced dissolution and
      reorganization of the solute. In situ imaging was also carried out on the
      crystals, revealing etch-pit formation during dissolution, and rapid growth at
      higher levels of supersaturation (sigma), both of which are direct consequences
      of the hydrophilic nature of the (1 0 0) face. Also presented here are nanoscale
      observations of the effect of octanoic acid, a structurally-related habit
      modifier, on crystalline adipic acid. Using AFM, we have been able to show that
      the presence of octanoic acid at low concentration has little observable affect
      on the development of the (1 0 0) face; however, as this concentration is
      increased, there are clear changes in step morphology and growth mode on the (1 0
      0) face of the crystal. At a concentration of 1.26 mmol dm(-3) (a concentration
      corresponding to a molar ratio of approximately 1:175 octanoic acid:adipic acid),
      growth on the (1 0 0) face is inhibited, with in situ AFM imaging indicating this
      is a direct consequence of octanoic acid binding to the surface, and pinning the
      monomolecular growth steps.

PMID- 15265560
TI  - Solid state NMR and DSC methods for quantifying the amorphous content in solid
      dosage forms: an application to ball-milling of trehalose.
AB  - The purpose of this study was to determine quantitatively the amorphous fraction
      in crystalline-amorphous powder mixtures of trehalose, in order to assess the
      ability of the (13)C NMR technique for quantitative amorphous characterization.
      The NMR method is described in detail and its accuracy is compared to that of the
      DSC technique. Amorphous trehalose was prepared by mechanical milling. Samples
      with different amorphous fractions were prepared by physical mixing of purely
      amorphous and purely crystalline powders. The results reveal a close correlation
      between the imposed compositions of the physical mixtures and those determined by
      NMR and DSC, indicating that both are useful and accurate methods for
      compositional characterization of powders. The NMR method is then used to
      determine the evolution of the amorphous fraction in a trehalose powder, during a
      milling procedure which ultimately leads to a fully amorphous state.

PMID- 15265561
TI  - Enhanced paclitaxel bioavailability after oral administration of pegylated
      paclitaxel prodrug for oral delivery in rats.
AB  - The bioavailability and pharmacokinetic parameters of paclitaxel in a PEGylated
      paclitaxel prodrug were studied after the oral administration of paclitaxel (25,
      50, 100 mg/kg) and prodrug (87.5, 175, 350 mg/kg) in rats. The area under the
      plasma concentration-time curve (AUC) of paclitaxel by oral paclitaxel were 836,
      1,602 and 3,076 ng/mlh, which increased dose-dependently (P < 0.006, r = 0.9996).
      The AUCs of paclitaxel by the oral paclitaxel prodrug were 1,646, 3,079 and 5,998
      ng/mlh, also increased dose-dependently (P < 0.003, r = 0.9999). The AUC of
      paclitaxel by the intravenous administration of paclitaxel (2 mg/kg) was 3,992
      ng/mlh. The mean absolute bioavailability (AB%) of paclitaxel was 1.6% by the
      oral administration of paclitaxel. The mean AB% of paclitaxel by the prodrug was
      6.3%, which was 3.94-fold higher than the oral paclitaxel. The peak concentration
      of paclitaxel (C(max)) in the dose of 350 mg/kg (50 mg/kg as paclitaxel) of
      prodrug was 339 ng/ml, which was significantly higher (P < 0.01) than the dose of
      50 mg/kg of paclitaxel (104 ng/ml). At the same dose of paclitaxel, the AUC of
      paclitaxel in the prodrug resulted in a remarkable increase, approximately four
      fold compared to the oral paclitaxel. It might be considered that the
      significantly enhanced bioavailability of paclitaxel by the prodrug, which is
      water-soluble and easy to permeat through the intestinal mucosa, is due to the
      avoidance of being inhibited by p-glycoprotein efflux pump in the intestinal
      mucosa and reduction of metabolism by cytochrome-p-450 (CYP3A) in epitherial
      cells of small intestine. It appears that the development of oral paclitaxel
      preparations as a prodrug is possible, which will be more convenient than the IV
      dosage form.

PMID- 15265562
TI  - pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine
      A.
AB  - The purpose of this work was to improve the oral bioavailability of cyclosporine
      A (CyA) by preparation the CyA-pH sensitive nanoparticles. The CyA-pH sensitive
      nanoparticles were prepared by using poly(methacrylic acid and methacrylate)
      copolymer. The characterization and the dispersion state of CyA at the surface or
      inside the polymeric matrices of the nanoparticles were investigated. The in
      vitro release studies were conducted by ultracentrifuge method. The
      bioavailability of CyA from nanoparticles and Neoral microemulsion was assessed
      in Sprague-Dawley (SD) rats at a dose of 15 mg/kg. The particle size of the
      nanoparticles was within the range from 37.4 +/- 5.6 to 106.7 +/- 14.8 nm. The
      drug entrapped efficiency was very high (from 90.9 to 99.9%) and in all cases the
      drug was amorphous or molecularly dispersed within the nanoparticles polymeric
      matrices. In vitro release experiments revealed that the nanoparticles exhibited
      perfect pH-dependant release profiles. The relative bioavailability of CyA was
      markedly increased by 32.5% for CyA-S100 nanoparticles (P < 0.05), and by 15.2%
      and 13.6% for CyA-L100-55 and CyA-L100 nanoparticles respectively, while it was
      decreased by 5.2% from CyA-E100 nanoparticles when compared with the Neoral
      microemulsion. With these results, the potential of pH-sensitive nanoparticles
      for the oral delivery of CyA was confirmed.

PMID- 15265563
TI  - Nano-emulsion formulation using spontaneous emulsification: solvent, oil and
      surfactant optimisation.
AB  - Nano-emulsions consist of fine oil-in-water dispersions, having droplets covering
      the size range of 100-600 nm. In the present work, nano-emulsions were prepared
      using the spontaneous emulsification mechanism which occurs when an organic phase
      and an aqueous phase are mixed. The organic phase is an homogeneous solution of
      oil, lipophilic surfactant and water-miscible solvent, the aqueous phase consists
      on hydrophilic surfactant and water. An experimental study of nano-emulsion
      process optimisation based on the required size distribution was performed in
      relation with the type of oil, surfactant and the water-miscible solvent. The
      results showed that the composition of the initial organic phase was of great
      importance for the spontaneous emulsification process, and so, for the physico
      chemical properties of the obtained emulsions. First, oil viscosity and HLB
      surfactants were changed, alpha-tocopherol, the most viscous oil, gave the
      smallest droplets size (171 +/- 2 nm), HLB required for the resulting oil-in
      water emulsion was superior to 8. Second, the effect of water-solvent miscibility
      on the emulsification process was studied by decreasing acetone proportion in the
      organic phase. The solvent-acetone proportion leading to a fine nano-emulsion was
      fixed at 15/85% (v/v) with EtAc-acetone and 30/70% (v/v) with MEK-acetone
      mixture. To strength the choice of solvents, physical characteristics were
      compared, in particular, the auto-inflammation temperature and the flash point.
      This phase of emulsion optimisation represents an important step in the process
      of polymeric nanocapsules preparation using nanoprecipitation or interfacial
      polycondensation combined with spontaneous emulsification technique.

PMID- 15265564
TI  - Poly(diallyldimethylammonium chlorides) and their N-methyl-N-vinylacetamide
      copolymer-based DNA-polyplexes: role of molecular weight and charge density in
      complex formation, stability, and in vitro activity.
AB  - Poly(diallyldimethylammonium chlorides) (pDADMAC) of different molecular weights
      (5-244 kDa) and DADMAC/N-methyl-N-vinylacetamide (NMVA) copolymers (coDADMAC)
      with different composition (24-75 mol%) and therefore varying cationic charge
      densities were used to investigate the relationship between polymer structure,
      polyplex formation and stability, as well as their biological activity. All
      polymers interacted electrostatically with DNA to form polyplexes as detected by
      electrophoresis. Complexation and condensation of DNA by the polycations as well
      as protection of DNA against mechanical and enzymatic degradation were found to
      increase with higher molecular weights and charge densities of the polymers as
      well as increasing charge ratios of the complexes. Static and dynamic light
      scattering revealed for all DNA/polymer complexes sphere-like structures of about
      100-150 nm forming more compact structures with increasing charge ratios which
      were stable over 24 h. The in vitro cytotoxicity of the free polymers determined
      by MTT-assay was directly correlated to molecular weight and charge density of
      the polycations which was also confirmed for polymer/DNA complexes quantifying
      the membrane toxic effects by LDH-release. The transfection efficiency of the
      complexes was low independent from different charge ratios, presence or absence
      of serum and lysosomotropic agents. In conclusion, the DADMACs are an interesting
      tool to study structure-function-relationships due to the specific adjustment of
      molecular weight as well as number and density of charges.

PMID- 15265565
TI  - Molecular epidemiology of Giardia and Cryptosporidium infections in dairy calves
      originating from three sources in Western Australia.
AB  - A longitudinal study was undertaken to determine the spread of naturally acquired
      Giardia and Cryptosporidium in dairy cattle in Western Australia. Samples were
      collected weekly from birth to weaning, and only calves that were sampled four or
      more times were included in the analysis. It was found that calves rapidly
      acquire infections with Cryptosporidium parvum and Giardia, with Cryptosporidium
      being the first to appear within 1-3 weeks after birth whereas Giardia was most
      prevalent in calves 4-7 weeks of age. Cryptosporidium and Giardia were detected
      in 48 and 89% of sampled calves, respectively. No significant association was
      observed in the present study between parasite occurrence and season or
      management practices (housing), and calf-to-calf contact appears to be the most
      likely source of transmission. Molecular characterization of isolates of Giardia
      and C. parvum recovered from calves demonstrated that only the occurrence
      Cryptosporidium represents a public health risk in terms of the potential for
      zoonotic transmission.

PMID- 15265566
TI  - Seroprevalence of Neospora spp. in asymptomatic horses in Italy.
AB  - One hundred and fifty horses from Italy were tested for serum antibodies to
      Neospora caninum by indirect fluorescence antibody test (IFAT). Antibodies were
      present in 42 horses (28%). The positive titres were: 1:50 (16/150-10.5%), 1:100
      (26/150-17%), 1:200 (8/150-5.3%) and 1:800 (1/150-0.6%). No neurological
      anomalies were observed in the seropositive horses. This is the first serologic
      survey for Neospora spp. antibodies performed on horses born and raised in Italy.

PMID- 15265567
TI  - Molecular and phylogenetic characterization of Theileria spp. parasites in
      autochthonous bovines (Mirandesa breed) in Portugal.
AB  - A survey was conducted during the months of April-June 2003 in the northeast
      Portugal (Braganca district) in order to characterize the hemoparasite population
      of an autochthonous Mirandesa breed of Bos taurus. The polymerase chain reaction
      (PCR) analysis of the bovine blood revealed that 3 out of 116 animals were
      infected with Theileria and/or Babesia parasites, while reverse line blot
      hybridisation (RLB) analysis showed that these animals were infected with
      Theileria buffeli/orientalis. Cloning and sequencing confirmed the RLB results.
      Database sequence searches combined with phylogenetic analysis of the partial 18S
      ribosomal RNA gene sequences obtained enabled us to place the parasites in
      question as members of the T. buffeli/orientalis group, confirming the PCR/RLB
      diagnosis.

PMID- 15265568
TI  - Comparison of three techniques for the serological diagnosis of Neospora caninum
      in the dog and their use for epidemiological studies.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed in our laboratory and
      used to determine the seroprevalence of Neospora caninum in three different dog
      populations in Belgium: healthy dogs from cattle farms and urban dogs with or
      without various neurological disorders. The test was validated and compared with
      two other tests: an indirect fluorescent antibody test (IFAT) and a commercially
      available competitive enzyme-linked immunosorbent assay (C-ELISA). The study
      showed a good correlation between the IFAT and the ELISA developed. When the two
      tests were compared with the C-ELISA, moderate positive and negative agreement
      indices were observed. Using our ELISA and the IFAT techniques, a high prevalence
      was found in farm dogs. This result showed that the neurological symptoms are not
      usually associated with the Neospora infection. In conclusion, the ELISA
      developed in our laboratory could replace the IFAT for the screening of a large
      number of dogs' sera.

PMID- 15265569
TI  - Prevalence of anti-Neospora caninum antibodies in dogs from urban, periurban and
      rural areas of the city of Uberlandia, Minas Gerais--Brazil.
AB  - In Brazil there are few reports on the prevalence of anti-Neospora caninum
      antibodies in dogs from urban, periurban and rural areas. Serum samples from 450
      dogs, 300 from urban, 58 from periurban and 92 from rural areas, were tested for
      the detection of anti-N. caninum IgG antibodies using IFAT: indirect fluorescent
      antibody test (IFAT, > or =50). Antibodies were observed in 63 (14%) of the 450
      serum samples analyzed, with 32 (10.7%) in dogs coming from the urban area, 11
      (18.9%) from the periurban area and 20 (21.7%) from the rural area. Statistical
      differences were seen between the occurrences in animals from the urban area and
      those of the rural area (P = 0.01). The antibody titers found were: 1:50 in 20
      dogs, 1:100-1:800 in 41 dogs, and 1:3200 in two dogs. In the female dogs, a
      smaller prevalence of dogs with antibodies was observed in those from the urban
      area (7.5%) in comparison with those of the rural (21.0%) (P = 0.05) and
      periurban (23.3%) (P = 0.01) areas. There were growing levels of antibody
      prevalence with the increase in age of the dogs in all three areas studied.
      Although this increase was not significant, it indicates a tendency towards more
      infections with age, suggesting post-natal exposure to N. caninum. However, a
      significant difference (P = 0.05) was observed in the occurrence of anti-N.
      caninum antibodies in dogs with ages = 2 years in urban (13.1% urban) versus
      rural environments (27.1% rural). Among the other age brackets studied the
      difference was not significant. The results confirm the presence of N. caninum in
      the region and reveal the important role of dogs in the parasite's epidemiology.

PMID- 15265570
TI  - Detection and identification of equine Theileria and Babesia species by reverse
      line blotting: epidemiological survey and phylogenetic analysis.
AB  - Specific oligonucleotide probes were designed to develop a new and highly
      sensitive reverse line blot assay to detect and identify simultaneously different
      Theileria and Babesia species in horses. The amplified hypervariable V4 region of
      the 18S rRNA gene was hybridised against different generic and species-specific
      probes. The survey was conducted over 243 samples of equine blood divided into
      three different groups: group 1, 24 horses presented as possible clinical
      piroplasmosis; group 2, 181 clinically healthy free-ranging horses exposed to
      ticks; group 3, 38 riding horses with unrelated pathologies and low or no contact
      with ticks. The study demonstrated a high piroplasm prevalence in the first two
      groups of animals. Two Theileria genotypes sharing 96.8% similarity between their
      18S rRNA gene sequences and two Babesia genotypes sharing 97.4% similarity, were
      identified. The biologic meaning of such genotypes is discussed in terms of their
      phylogenetic relationships and potential pathogenicity.

PMID- 15265571
TI  - CpG-oligodeoxynucleotides enhance porcine immunity to Toxoplasma gondii.
AB  - Protection against a challenge infection with Toxoplasma gondii VEG strain
      oocysts was examined in pigs after vaccination with T. gondii RH strain
      tachyzoites with or without a porcine specific synthetic oligodeoxynucleotides
      (ODN) containing immunostimulatory CpG motifs. Six groups of pigs were immunized
      with incomplete Freund's adjuvant (IFA) and either vehicle, tachyzoites alone or
      in combination with three different doses of CpG ODN or with CpG ODN alone.
      Protection from challenge was significantly (P < 0.05) improved in pigs
      vaccinated using CpG ODN as an adjuvant with tachyzoites compared to all other
      groups. The CpG ODN tachyzoite-immunized pigs also had higher serum parasite
      specific IgG antibody, no clinical signs of disease, and 52% had no demonstrable
      tissue cysts after the challenge infection. These data indicate that CpG ODN is a
      potential safe and effective adjuvant for the T. gondii RH strain vaccine in
      pigs.

PMID- 15265572
TI  - Isolation of two antigens from Trypanosoma evansi that are partially responsible
      for its cross-reactivity with Trypanosoma vivax.
AB  - In Venezuela, two non-tsetse transmitted trypanosomes, Trypanosoma evansi and
      Trypanosoma vivax, are the major etiological agents of animal trypanosomosis.
      Rodents can be experimentally infected with T. evansi in order to obtain enough
      parasites to prepare antigens for serological tests. On the contrary, the
      production of T. vivax antigens is a limiting factor in most laboratories. Since
      T. evansi and T. vivax have exhibited a very high immunological cross-reactivity,
      we have focused on the identification of antigens from T. evansi responsible for
      this phenomenon. The predominant 64 kDa glycosylated cross-reacting antigen was
      recently purified from the TEVA1 T. evansi Venezuelan isolate [Parasitology 124
      (2002) 287]. Here, we purified two additional cross-reacting antigens with
      molecular masses of approximately 51 and 68 kDa from the cytosolic fraction of
      the same T. evansi isolate, by sequential chromatography on DEAE-sepharose and
      sephacryl S-300. Sera obtained from animals infected with T. evansi or T. vivax
      recognized both purified proteins, suggesting their potential use as diagnostic
      reagents.

PMID- 15265573
TI  - Glomerulonephritis in water buffaloes (Bubalus bubalis) naturally infected by
      Fasciola hepatica.
AB  - Glomerulonephritis caused by Fasciola hepatica was observed in buffaloes. Renal
      biopsies of 20 buffaloes, 11 with F. hepatica and 9 uninfected buffaloes
      (controls), were examined by light microscopy, direct and indirect
      immunofluorescence, and immunohistochemical analysis. The biopsies of seven
      (63.6%) infected buffaloes revealed membranoproliferative glomerulonephritis,
      three biopsies (27.3%) showed mesangioproliferative glomerulonephritis, and one
      kidney presented normal biopsy specimens. In the control group, seven buffaloes
      (77.8%) presented normal biopsy specimens, while two (22.2%) revealed
      glomerulonephritis-one with a membranoproliferative pattern, and the other with a
      mesangioproliferative pattern-with extensive inflammatory cell infiltrate. Our
      conclusion is that glomerulopathy is associated with fascioliasis and that
      buffaloes are suitable as a naturally existing experimental model of renal injury
      by circulating immune complexes.

PMID- 15265574
TI  - Herd-level seroprevalence of fasciolosis in cattle in north central Portugal.
AB  - An epidemiological study of Fasciola hepatica in cattle was implemented in the
      north central region of Portugal. Both an enzyme-linked immunosorbent assay and
      an egg shedding quantification technique were used in the follow-up of seven
      herds. Two of these herds were negative and the other five were positive for F.
      hepatica. A herd cut-off of value of 0.425 optical density was calculated and
      herd sensitivity (HSe) and herd specificity (HSp) were defined. Three
      seroprevalence studies were also implemented in the region with stratification by
      county sub-regions for a period of 18 months. Overall mean herd prevalence in
      Vagos of 11, 23 and 48% was progressively found for the three studies,
      respectively.

PMID- 15265576
TI  - The influence of flotation solution, sample dilution and the choice of McMaster
      slide area (volume) on the reliability of the McMaster technique in estimating
      the faecal egg counts of gastrointestinal strongyles and Dicrocoelium dendriticum
      in sheep.
AB  - The present study was aimed to evaluate the influence of flotation solution,
      sample dilution, and the choice of McMaster slide area (volume) on the
      reliability of the McMaster technique in estimating the faecal egg counts of
      gastrointestinal (GI) strongyles and Dicrocoelium dendriticum in a composite
      sample of faeces from naturally infected sheep. Fourteen flotation solutions
      having densities between 1.200 and 1.450, and six sample dilutions, 1:10, 1:15,
      1:20, 1:30, 1:40 and 1:50 were used. Each of the six dilutions was divided into
      70 aliquots in order to have five replicates of each of the 14 flotation
      solutions at each of the six dilutions. For each McMaster slide, the GI strongyle
      and D. dendriticum egg counts were performed under one grid (McM 0.15 ml), two
      grids (McM 0.3 ml), one chamber (McM 0.5 ml), and both chambers (McM 1.0 ml).
      Mean eggs per gram (EPG) of faeces of GI strongyles and D. dendriticum were
      calculated and statistical analyses were performed on the resulting data. The
      type of flotation solution used significantly influenced the EPG in the GI
      strongyles and in the D. dendriticum egg counts. All the sucrose-based solutions
      at density between 1.200 and 1.350 floated more GI strongyle eggs than the
      others. With respect to D. dendriticum, only six solutions were capable of
      floating eggs and the potassium iodomercurate solution (density 1.440) floated
      more eggs than the others. The reliability of the McMaster technique regarding
      sample dilution was high for both GI strongyle and D. dendriticum EPG at 1:10 and
      1:15, and then progressively decreased with increasing dilution. The reliability
      of the McMaster technique regarding the choice of the McMaster slide area
      (volume) was high for both GI strongyle and D. dendriticum EPG at the McMaster
      slide area (volume) of 1.0 ml, i.e. the total area of the McMaster slide. The EPG
      counts resulting from choosing any of the other three McMaster slide areas
      (volumes), i.e. McM 0.15 ml, McM 0.3 ml, or McM 0.5 ml, produced unreliable over
      estimates. The findings of the present study show that the highest reliability of
      the McMaster technique for estimating GI strongyle and D. dendriticum egg counts
      in faeces from pastured sheep is obtained when using flotation solutions based on
      sucrose for GI strongyles, and potassium iodomercurate for D. dendriticum,
      dilutions which do not exceed 1:15, and the McMaster slide area (volume) of 1.0
      ml.

PMID- 15265575
TI  - Validation of the FAMACHA eye color chart for detecting clinical anemia in sheep
      and goats on farms in the southern United States.
AB  - Recent studies on sheep and goat farms in the southern United States indicate
      that multiple-anthelmintic resistance in Haemonchus contortus is becoming a
      severe problem. Though many factors are involved in the evolution of resistance,
      the proportion of the parasite population under drug selection is believed to be
      the single most important factor influencing how rapidly resistance develops.
      Therefore, where prevention of resistance is an important parallel goal of worm
      control, it is recommended to leave a portion of the animals untreated. Recently,
      a novel system called FAMACHA was developed in South Africa, which enables
      clinical identification of anemic sheep and goats. When H. contortus is the
      primary parasitic pathogen, this system can be applied on the farm level to
      reduce the number of treatments administered, thereby increasing the proportion
      of the worm population in refugia. Since most studies validating the FAMACHA
      method have been performed in South Africa, it is important that the method be
      tested in other regions before its use is broadly recommended. We performed a
      validation study of FAMACHA by testing the system in sheep (n = 847) and goats (n
      = 537) of various breeds and ages from 39 farms located in Arkansas, Georgia,
      Louisiana, Florida, and the US Virgin Islands. The color of the ocular
      conjunctiva of all animals were scored on a 1-5 scale using the FAMACHA card, and
      blood samples were collected from each animal for determination of packed cell
      volume (PCV). Fecal samples were also collected from a majority of the animals
      tested for performance of fecal egg counts (FEC). Correlations between PCV and
      eye scores, PCV and FEC, and FEC and eye scores were all highly significant for
      both sheep and goats (P < 0.001). Data for both FAMACHA scores and PCV were
      evaluated using two separate criteria for anemia: eye score values of 3, 4 and 5
      or 4 and 5, and PCV values of < or =19 or < or =15 were considered anemic.
      Specificity was maximized when eye score values of 4 and 5 were considered anemic
      and PCV cut off for anemia was < or =19, but sensitivity was low. In contrast,
      sensitivity was 100% for both sheep and goats when eye score values of 3, 4 and 5
      were considered anemic and PCV cut off was < or =15, but specificity was low. In
      both sheep and goats, predictive value of a negative was greater than 92% for all
      anemia and eye score categories, and was greater than 99% for both eye score
      categories when an anemia cutoff of < or =15 was used. Predictive value of a
      positive test was low under all criteria indicating that many non-anemic animals
      would be treated using this system. However, compared to conventional dosing
      practices where all animals are treated, a large proportion of animals would
      still be left untreated. These data indicate that the FAMACHA method is an
      extremely useful tool for identifying anemic sheep and goats in the southern US
      and US Virgin Islands. However, further studies are required to determine optimal
      strategies for incorporating FAMACHA-based selective treatment protocols into
      integrated nematode control programs.

PMID- 15265577
TI  - A survey of gastrointestinal helminths in cats of the metropolitan region of Rio
      de Janeiro, Brazil.
AB  - The prevalence of gastrointestinal helminth parasites in 135 cats over 1 year of
      age and inhabiting the metropolitan region of the city of Rio de Janeiro, Brazil
      was investigated by necropsy. These animals had two distinct origins: 99 cats (29
      males and 70 females) were derived by capture in public areas (feral/stray) and
      36 (12 males and 24 females) from shelters. The overall prevalence of
      gastrointestinal helminth parasites was 89.6%. The following parasites, with
      their respective prevalence in parenthesis, were found: Dipylidium caninum
      (52.6%), Ancylostoma braziliense (65.9%), Ancylostoma tubaeforme (8.9%), Toxocara
      cati (25.2%), Toxascaris leonina (11.9%), Physaloptera praeputialis (9.6%).
      Concurrent infections with two or more parasites were recorded in 59.5% of the
      individuals. Of the 121 parasitized cats, 94 were feral/strays and 27 were from
      shelters. Among feral/stray cats, 80 were infected with A. braziliense (85%) and
      17 of the shelter felids were infected with D. caninum (63%). Feral/stray cats
      had higher worm intensities (6411/94-68.2) than shelter cats (992/27-36.7). The
      helminth parasites most frequently found in feral/stray cats were Ancylostoma
      braziliense (47.5%) and D. caninum (47%) while in shelter cats, D. caninum was
      the predominant species (85.2%). Twenty seven cats (22.3%) had only A.
      braziliense and 19 (15.7%) were parasitized only with D. caninum. Among those
      cats harboring mixed infections A. braziliense and D. caninum were the species
      more frequently found (P < 0.001).

PMID- 15265578
TI  - p-Nitrotoluene causes hyperactivity in the rat.
AB  - It has not been known which endocrine disruptors exert their effects on neuronal
      functions, particularly leading to behavioral alterations. To address this, we
      examined the effects of p-nitrotoluene, an endocrine disruptor, on rat behavior
      and gene expression. Single intracisternal administration of p-nitrotoluene (ca.
      10 microg) into 5-day-old male Wistar rats caused significant hyperactivity at 4
      5 weeks of age. They were about 1.4-fold more active in the nocturnal phase after
      administration of p-nitrotoluene than control rats. Based on DNA array analyses,
      p-nitrotoluene decreased more than two-fold the levels of gene expression of the
      mesencephalic dopamine transporter at 8 weeks old. Thus, it was demonstrated for
      the first time that p-nitrotoluene definitely affected the developing brain,
      resulting in hyperactivity in the rat.

PMID- 15265579
TI  - Effects of ventilation on body sway during human standing.
AB  - Body sway was studied in standing with eyes closed during quiet breathing and
      apnoea. The hypothesis was that absence of ventilation improved balance.
      Performance and control of balance were assessed by centre of gravity and centre
      of pressure motions respectively. Eight healthy male subjects participated in the
      study. The analysis was performed for the first 20s when no activity of the
      diaphragm and no force variation at thoracic and abdominal levels were observed
      in apnoea condition. Performance and control were significantly improved in
      apnoea from 17 to 26% for the planar parameters; this improvement was only
      observed along the medio-lateral axis (around 34%), probably due to upper body
      asymmetry and diminution of the number of degrees of freedom that can be
      mobilised along this axis. In conclusion, ventilation in quiet breathing is a
      perturbing factor in human standing.

PMID- 15265580
TI  - Induction of memory-associated immediate early genes by nerve growth factor in
      rat primary cortical neurons and differentiated mouse Neuro2A cells.
AB  - Activation of several immediate early genes (IEGs) is crucial for long-term
      memory formation in vivo. In vitro methods of inducing these genes have not been
      investigated extensively. Here we present data demonstrating that application of
      the neurotrophin, nerve growth factor (NGF), to both rat primary neuronal
      cultures and differentiated mouse neuroblastoma 2A (N2A) cultures reliably
      induces expression of several IEGs, including Zif268, Nur77 and Arc, each of
      which have been linked to memory consolidation. These findings provide an in
      vitro model in which to test other agents that might modulate the induction of
      memory-associated genes.

PMID- 15265581
TI  - Protein 4.1B localizes on unmyelinated axonal membranes in the mouse enteric
      nervous system.
AB  - Recent molecular studies on anchoring structures between myelin sheaths by glial
      cells (oligodendrocytes and Schwann cells (Sc) in the central (CNS) and
      peripheral nervous system (PNS), respectively) and axons indicated protein
      protein interaction for the polarization of paranodes in the axons. The protein
      4.1 (4.1) family was originally found in erythrocytes as a component of membrane
      skeletons, and genetic approaches revealed the precise family members. One of
      them, 4.1B, has been reported to be localized in paranodes and juxtaparanodes of
      myelinated axons. In this study, in addition to the myelinated axons, we also
      present the localization of 4.1B in nerve fibers in the adult mouse enteric
      nervous system, a subpopulation of mature unmyelinated nerve fibers in PNS.
      Ultrastructurally, 4.1B localized along the membranes of unmyelinated axons. Such
      unmyelinated axons were surrounded only by Sc, suggesting that the 4.1B may also
      have a role in direct Sc-axon interactions and maturation of the axons, as well
      as myelinating glial cell-axon interactions.

PMID- 15265582
TI  - Effects of normal aging on event-related desynchronization/synchronization during
      a memory task in humans.
AB  - Event-related desynchronization (ERD) and event-related synchronization (ERS) of
      the 1-20Hz EEG frequencies were studied using wavelet transforms in young (n =
      10, mean age 22) and elderly subjects (n = 10, mean age 65) performing an
      auditory Sternberg memory task with words as stimuli. In both age groups,
      encoding of the four-word memory set elicited ERS in the theta and alpha
      frequency range. Theta ERS, and ERD in the alpha and beta bands were observed
      during retrieval. During encoding, the elderly showed greater alpha ERS and
      smaller theta ERS. During retrieval, smaller alpha ERD and theta ERS was found in
      the elderly subjects. Also, in the elderly, beta ERD was elicited in the late
      time window during retrieval. The statistically significant differences between
      the age groups were more marked during retrieval than during encoding. The
      results indicate that although the two groups performed equally well behaviorally
      in the task and the elderly subjects were cognitively intact, normal aging
      affects oscillatory theta, alpha and beta responses particularly during retrieval
      from working memory. The ERD/ERS patterns of the elderly resemble those of
      children found in a recent study, which might suggest that those memory-related
      brain processes that evolve later in childhood are the first to be affected in
      older age.

PMID- 15265583
TI  - Erythropoietin prevents hypoxia/ischemia-induced DNA fragmentation in an
      experimental model of perinatal asphyxia.
AB  - Erythropoietin (EPO) prevents neuronal damage following ischemic, metabolic and
      excitotoxic stress. Recent studies have shown that EPO plays a significant role
      in the developing brain. The present study investigates the effect of EPO
      administration on hypoxic-ischemic brain injury and the possibility that its
      neuroprotective action may be associated with anti-apoptotic activity. Seven-day
      old rats were treated with EPO (2000 U/kg) and subjected to a modified Levine
      procedure. EPO administration before the hypoxic-ischemic insult significantly
      reduces the severity of brain damage and improved the short-term functional brain
      recovery. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling and DNA electrophoresis displayed no evidence of DNA fragmentation in
      EPO-treated animals. These results suggest that EPO might protect the neonatal
      rat brain by anti-apoptotic mechanisms.

PMID- 15265584
TI  - Presence of translation elongation factor-1A (eEF1A) in the excitatory
      postsynaptic density of rat cerebral cortex.
AB  - The postsynaptic density (PSD) is a proteinaceous cellular structure that is
      specialized for postsynaptic signal transduction. Here, we show that eukaryotic
      translation factor-1A (eEF1A; formerly known as eEF-1alpha) is associated with
      the excitatory PSD in rat forebrain. Immunoblot analysis showed that eEF1A in the
      PSD fraction is enriched over homogenate. Salt (1.0M NaCl), but not non-ionic
      detergents such as Triton X-100 (1.0%) and n-octyl glucoside (1.0%), could
      dissociate eEF1A from the PSD core. In cultured cortical neurons, eEF1A was
      colocalized with postsynaptic markers (PSD95 and SynGAPalpha), but not with a
      presynaptic marker (synaptophysin). These results indicate that eEF1A is present
      in the PSD of the excitatory synapses.

PMID- 15265585
TI  - Acute cardiac injury induces glial cell response and activates extracellular
      signaling-regulated kinase-1 and -2 in the spinal cord of Wistar rats.
AB  - We have examined the activation of glial cells and the upregulation of
      phosphorylated extracellular signaling-regulated kinase (ERK)-1 and -2 in upper
      thoracic segments of the spinal cord in rats following acute cardiac injury
      (ACI). ACI was established by intramyocardial injection of formalin and confirmed
      by hematoxylin and eosin (H&E) and terminal transferase-mediated deoxyuridine
      triphosphate-biotin nick end labeling (TUNEL) staining. Following ACI, the
      astrocytes (determined by glial fibrillary acidic protein (GFAP) immunoreactivity
      (-IR)) and microglia (determined by OX-42-IR) were activated within the thoracic
      spinal cord. Phosphorylated (phospho-) ERK-IR was also activated in response to
      ACI. The upregulation of phospho-ERK was observed at 1h and became very obvious
      at 6h following ACI. The upregulated phospho-ERK was evidently expressed in the
      superficial and deep dorsal horn of the thoracic spinal cord. The activated ERK
      was also expressed in the intermediolateral nucleus (IML), nucleus intercalatus
      (IC) and the long processes projecting to the central canal, regions closely
      associated with autonomic outflow. Thus, the present study suggested that ACI
      could induce the activation of spinal ERK, which might link the nociceptive
      processing with the spinal sympathetic reflexes in myocardial injury in clinics.

PMID- 15265586
TI  - Multiple sources of endogenous opioid peptide involved in the hypoglycemic
      response to 15 Hz electroacupuncture at the Zhongwan acupoint in rats.
AB  - A decrease in plasma glucose levels was observed in rats which received
      electroacupuncture (EA) stimulation at the Zhongwan acupoint. In the present
      study, the role of the adrenal gland in this hypoglycemic response to EA at high
      frequency (15 Hz) was investigated on adrenalectomized (ADX) normal rats. There
      was a sharper decrease in plasma glucose by EA stimulation in the fasting ADX
      group than in the fasting sham-operated group. Naloxone blocked this hypoglycemic
      response to EA stimulation in rats which received ADX. Stimulation of EA failed
      to elicit an increase in plasma beta-endorphin and insulin levels in ADX rats.
      Similar results were observed in sham and ADX mice. EA stimulation of ADX mice
      can reduce plasma glucose levels. Furthermore, naloxone abolished the
      hypoglycemic response to EA stimulation in mice. Such a hypoglycemic response to
      EA stimulation was also observed in micro-opioid receptor knockout mice (MOR
      KOM). Mediation by another opioid peptide should also be considered in future
      experiments. We conclude that multiple sources of endogenous opioid peptide
      participated in the lowering of plasma glucose in rats induced by EA stimulation
      at higher frequency (15 Hz) at the Zhongwan acupoint. Increase in beta-endorphin
      levels from the adrenal gland enhances the secretion of insulin, there by
      reducing plasma glucose levels, and is partially involved in this EA stimulation.

PMID- 15265587
TI  - An increase in cAMP concentration in mouse hippocampal slices exposed to low
      frequency and pulsed magnetic fields.
AB  - Our previous studies revealed that magnetic fields amplified evoked potentials
      recorded from mouse hippocampal slices. In search for the mechanism of this
      effect, we evaluated the concentration of cAMP in slices exposed to low-frequency
      and pulsed magnetic fields. Low-frequency magnetic fields of 15 mT applied at
      0.16 Hz for 30 min enhanced the concentration of cAMP almost three-fold. The
      concentration of cAMP continued to rise through the first hour after turning
      magnetic fields off, reaching almost a four-fold increase, and then returned to
      control levels at the end of the second hour. Neither static magnetic fields nor
      magnetic fields applied with the frequency of 0.5 Hz had any effect on cAMP
      concentration. The increase in cAMP levels was dependent on the strength of the
      magnetic field and required the presence of extracellular calcium. A pulsed
      magnetic field applied with variable intensity (9-15 mT) and in cycles lasting
      from 5 to 20 min doubled the cAMP concentration. These results support our
      previous electrophysiological observations and provide biochemical correlates for
      their interpretation.

PMID- 15265588
TI  - Identification of adenosine A1 and A3 receptor subtypes in rat pial and
      intracerebral arteries.
AB  - The expression and microanatomical localization of adenosine A1 and A3 receptor
      subtypes were investigated in rat pial and intracerebral arteries by
      immunoblotting, immunohistochemistry and in situ hybridization techniques. Pial
      artery membranes develop immune bands of approximately 79 and 52 kDa when exposed
      to anti-A1 and anti-A3 receptor protein antibodies respectively. Sympathectomy
      performed by bilateral superior cervical ganglionectomy did not change the
      pattern of adenosine A1 or A3 receptor immunochemistry. Sections of pial and
      intracerebral arteries processed for A1 or A3 receptor protein
      immunohistochemistry developed immune reaction in the tunica media, within
      arterial smooth muscle. A1 receptor immunoreactivity was more pronounced in large
      sized compared to medium- and small-sized pial arteries and was stronger in small
      than in medium- or large-sized intracerebral arteries. A3 receptor
      immunoreactivity was more pronounced in smaller sized pial arteries compared to
      larger pial arteries, whereas no differences in the intensity of immune staining
      were noticeable between different sized intracerebral arteries. In situ
      hybridization histochemistry revealed a strong signal for A1 receptor and a
      moderate signal for A3 receptor in the tunica media of pial arteries, within
      smooth muscle. The present study indicates that rat pial and intracerebral
      arteries besides to the well characterized A2a and A2b receptors, express also A1
      and A3 receptor subtypes. The identification of cerebrovascular A1 and A3
      adenosine receptor subtypes may stimulate further research for detailing the
      mechanism(s) of regulation of cerebral circulation by adenosine.

PMID- 15265589
TI  - Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from
      PC12 cells.
AB  - Parkinson's disease is characterized by an extensive loss of dopaminergic neurons
      in the substantia nigra pars compacta. The final common pathway in the demise of
      these cells may involve dopamine-dependent oxidative stress. Previous studies
      revealed a new neuronal protective role of ATP-sensitive potassium channel
      openers. But the exact mechanism is still unknown. In the present study, the
      neuroprotective effect of iptakalim, a novel ATP-sensitive potassium channel
      opener, was studied against rotenone-induced cytotoxicity in rat dopaminergic
      PC12 cells. Rotenone decreased cell viability significantly after 48 h exposure
      and induced dopamine release from PC12 cells concentration-dependently. Iptakalim
      significantly enhanced dopamine uptake and alleviated rotenone-induced PC12 cells
      death and reduced dopamine release induced by rotenone or GBR-12909, a classical
      dopamine transporter inhibitor. These results suggest that iptakalim may open
      mitochondrial K(ATP) channels to modulate dopamine transporter and reduce
      extracellular dopamine levels, thereby it protecting PC12 cells against rotenone
      induced injury.

PMID- 15265590
TI  - Age-related effects of bilateral frontal eye fields lesions on rapid eye
      movements during REM sleep in rhesus monkeys.
AB  - Rapid eye movement (REM) is one of the most characteristic features of REM sleep,
      but the mechanisms underlying its regulation remain unclear. The present study
      aims to investigate whether the frontal eye field (FEF) is involved in the
      regulation of the rapid eye movements during REM sleep. To address this question,
      we ablated the FEF in four rhesus monkeys and observed the effects of the lesions
      on sleep architecture. After lesions, two adult monkeys did not show any lesion
      effect. However, in the other two adolescent monkeys, both the total duration and
      percentage of the rapid eye movements during REM sleep were decreased moderately.
      The result suggests that the relation between the FEF and the regulation of the
      rapid eye movements during REM sleep may be affected by age factor, also
      indicating that both the functions of the FEF and the mechanisms underlying the
      control of rapid eye movements during REM sleep might not be the same throughout
      the whole life span of an animal.

PMID- 15265591
TI  - Proprioceptive weighting changes in persons with low back pain and elderly
      persons during upright standing.
AB  - The purpose of this study was to examine whether postural instability observed in
      persons with spinal pain and in elderly persons is due to changes in
      proprioception and postural control strategy. The upright posture of 20 young and
      20 elderly persons, with and without spinal pain, was challenged by vibrating
      ankle muscles (i.e. tibialis anterior, triceps surae) or paraspinal muscles.
      Center of pressure displacement was recorded using a force plate. Persons with
      spinal pain were more sensitive to triceps surae vibration and less sensitive to
      paraspinal vibration than persons without spinal pain. Elderly persons were more
      sensitive to tibialis anterior vibration than young healthy persons. These
      results suggest that spinal pain and aging may lead to changes in postural
      control by refocusing proprioceptive sensitivity from the trunk to the ankles.

PMID- 15265592
TI  - Protein levels of glycogen synthase 3 kinase are normal in progressive
      supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disorder
      characterized by pure neurofibrillary tau pathology involving mainly basal
      ganglia and brain stem nuclei. One of the kinases involved in tau phosphorylation
      is glycogen synthase 3 kinase (GSK3). In mammals GSK3 is present in two isoforms,
      alpha and beta regulated by phosphorylation: phosphorylation of Ser9 in GSK3beta
      or Ser21 in GSK3alpha leads to inactivation while phosphorylation of Tyr216 in
      GSK3beta or Tyr279 in GSK3alpha leads to activation. We analyzed the protein
      levels of GSK3alpha/beta and of the phosphorylated forms GSK3beta S(9), GSK3beta
      Y(216), GSK3alpha Y(279) in brain tissues of subjects with PSP. The analysis
      failed to show significant differences of all GSK3 isoforms in PSP in comparison
      to age-matched control cases. This negative result argues against the role of
      GSK3 in the pathogenesis of PSP.

PMID- 15265593
TI  - Habituation to galvanic vestibular stimulation for analysis of postural control
      abilities in gymnasts.
AB  - The possible correlation between postural control abilities in gymnasts and the
      sensitivity for and the degree of short-term habituation to galvanic vestibular
      stimulation (GVS) was studied. Seven balance trained young girls (Dutch National
      Junior Gymnasts Championship) versus seven non-trained girls and twenty-five
      women underwent computer-controlled GVS using a monaural continuous 1
      cosinusoidal stimulus of 0.5 Hz and 2 mA, repeated three times on each side
      [Balter, Stokroos, Boumans, Kingma, Acta Otolaryngol. (in press); Balter,
      Stokroos, Eterman, Paredis, Orbons, Kingma, Acta Otolaryngol. (in press)].
      Results showed that mean total galvanic-induced body sway (GBS) gain was
      significantly lower in the trained and untrained girls compared to the adult
      women (P < 0.05). Mean habituation to GVS (learning abilities), however, showed
      no significant differences between the three groups. We suggest that the superior
      balance control in professional gymnasts is primarily achieved through motor
      training and not by learning abilities or a higher sensitivity of the vestibular
      system [Neurosci. Lett. 225 (1998) 155].

PMID- 15265594
TI  - An experimental knee joint effusion does not affect plasma catecholamine
      concentration in humans.
AB  - Knee joint effusion causes quadriceps inhibition and is accompanied by increased
      soleus muscle excitability. In order to reverse the neurological alterations that
      occur to the musculature following effusion, we need to understand the extent of
      neural involvement. Ten healthy adults were tested on two occasions; during one
      session, subjects had their knees injected with saline and in the other
      admission, they did not. Soleus Hmax, Mmax, plasma epinephrine, and
      norepinephrine concentrations were obtained at five intervals. Results showed
      that Hmax increased following the effusion, while norepinephrine and epinephrine
      levels were not altered. We suggest that the soleus facilitation seen following
      knee effusion results from stimulation of joint mechanoreceptors and removal of
      descending spinal and supraspinal inhibition and is not the result of a
      sympathetic response.

PMID- 15265595
TI  - Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis.
AB  - Abeta peptides are naturally occurring peptides, which are thought to play a key
      role in the pathophysiology of Alzheimer's disease (AD). In AD cases, levels of
      soluble and insoluble Abeta peptides increase in the brain as well as in the
      cerebrovasculature, a phenomenon that does not occur in extra-cranial vessels.
      There are frequently anomalies in the cerebrovasculature in AD, and despite
      increases in several pro-angiogenic factors in AD brain, evidence for increased
      vascularity is lacking; in fact there is evidence to the contrary. It has also
      been recently shown that Abeta peptides may have profound anti-angiogenic effects
      in vitro and in vivo. We therefore investigated whether there is evidence for
      altered angiogenesis in the vasculature in a transgenic mouse model of Abeta
      amyloidosis (Tg APPsw line 2576). In vitro, the formation of capillary-like
      structures on a reconstituted extracellular matrix by endothelial cells isolated
      from Tg APPsw is impaired. Ex vivo, the sprouting of new capillaries from
      arterial explants (over expressing Abeta) isolated from 9-month-old Tg APPsw is
      reduced compared to arterial explants isolated from control littermates. In
      addition, Tg APPsw mice show a reduction in vascular density in the cortex and
      hippocampus compared to control littermates. Altogether, our data suggest that
      the over expression of APPsw in the vasculature may oppose angiogenesis.

PMID- 15265597
TI  - Decreased hypothalamic aromatization in female rats of true precocious puberty.
AB  - The true precocious puberty animal model induced by the single dose of danazol
      was used for investigating the expressions of hypothalamic aromatase in the
      advanced onset of puberty in rats. The day of vaginal opening and first estrus
      showed significant advancement in the model rats compared with the normal and
      vehicle rats (P < 0.01, respectively). The hypothalamic gonadotropin-releasing
      hormone (GnRH) mRNA expression increased significantly in the model rats compared
      with that in the normal and vehicle ones (P < 0.01). The levels of aromatase mRNA
      and protein expressions detected by RT-PCR and Western blot both decreased in the
      model rats compared with those in the normal and vehicle groups (P < 0.05). The
      results suggested that the hypothalamic aromatization might diminish in the onset
      of true precocious puberty of female rats.

PMID- 15265596
TI  - Antinociception induced by chronic exposure of rats to cigarette smoke.
AB  - To investigate if chronic exposure to cigarette smoke induces analgesia, rats
      were exposed to concentrated cigarette smoke in an environmental chamber over
      four successive 5-day blocks (6 h/day), with 2 smoke-free days between blocks. A
      control group was exposed to room air. Tail flick latencies increased
      significantly (analgesia) during each smoke exposure block, with a relative
      decline in analgesia across blocks (tolerance) and a return to control levels
      during the first three smoke-free interludes while remaining higher after the
      conclusion of the 4-week exposure period. Mechanical (von Frey) withdrawal
      thresholds declined over time in smoke-exposed and control groups, with the smoke
      exposed group showing significantly lower thresholds. Plasma nicotine reached
      95.4 +/- 32 (S.D.) ng/ml at the end of weekly smoke exposure and declined to 44.9
      +/- 10.6 ng/ml 24 h after withdrawal. Rats lost weight during smoke exposure and
      quickly regained weight during smoke-free interludes and at the cessation of
      smoke exposure. Analgesia may contribute to the initiation of smoking, and rapid
      reversal of the analgesic effect following acute exposure may contribute to the
      difficulty in quitting smoking.

PMID- 15265598
TI  - Differential inhibition of nicotine- and acetylcholine-evoked currents through
      alpha4beta2 neuronal nicotinic receptors by tobacco cembranoids in Xenopus
      oocytes.
AB  - In tobacco, there are two types of compounds that interact with neuronal
      nicotinic acetylcholine receptors (nnAChRs) in the brain. The first is the
      addictive component of tobacco and an agonist of these receptors, nicotine. The
      second are cyclic diterpenoids called cembranoids that non-competitively inhibit
      many types of nnAChRs. Nictotinic receptors composed of alpha4beta2 subunits are
      the predominant type of nicotinic receptors in the brain. These alpha4beta2
      receptors are up-regulated upon chronic exposure to nicotine and have been
      implicated in nicotine addiction. The present study was designed to determine
      whether the inhibitory effects of two cembranoids from tobacco [(1S, 2E, 4R, 6R,
      7E, 11E)-2,7,11-cembratriene-4,6-diol (4R) and its diastereoisomer (1S, 2E, 4S,
      6R, 7E, 11E)-2,7,11-cembratriene-4,6-diol (4S)] were comparable on acetylcholine
      (ACh) and nicotine-evoked currents through alpha4beta2 nnAChRs. alpha4beta2
      nnAChRs from rat brain were expressed in Xenopus oocytes and studied using the
      two-electrode voltage-clamp technique. The dose-response curves for acetylcholine
      and nicotine were hyperbolic and bell-shaped, respectively. Although there was no
      difference in the potency between cembranoids 4R and 4S, both of these
      cembranoids more potently inhibited nicotine-induced currents than acetylcholine
      induced currents. Furthermore, both cembranoids were more potent inhibitors of
      this receptor when they were preincubated for 1 min prior to application of
      agonist. The finding that cembranoids preferentially inhibit nicotine-induced
      currents over those elicited by the natural neurotransmitter acetylcholine may
      have important implications when developing strategies to prevent nicotine
      addiction and tobacco use.

PMID- 15265599
TI  - Optical mapping of pontine chemosensitive regions of neonatal rat.
AB  - We analyzed the neuronal response to hypercapnic acidosis, using an optical
      recording technique with a fluorescent voltage-sensitive dye (di-4-ANEPPS), in
      pontine slice preparations of neonatal rats, containing the locus coeruleus (LC),
      which has been electrophysiologically demonstrated to be chemosensitive. The dye
      stained preparation was continuously superfused with artificial cerebrospinal
      fluid. Epifluorescence of the slice was detected using a high-sensitivity optical
      recording system. Changes in the intensity of fluorescence were serially analyzed
      while switching artificial cerebrospinal fluid from control to hypercapnic
      acidosis, or vice versa. The optical recording method revealed that the LC, as
      reported in previous studies, reversibly showed a depolarizing response to
      hypercapnic acidosis in 56% of the examined preparations. The A5 area (56%) also
      exhibited a reversible, depolarizing response to hypercapnic acidosis. The
      response was preserved under conditions in which chemical synaptic transmission
      was blocked by low Ca(2+)-high Mg(2+) solution. These results suggest that the
      optical recording method is applicable to identification of potentially
      chemosensitive areas, which deserve further electrophysiological analysis, and
      that the A5 area could be chemosensitive.

PMID- 15265600
TI  - Antisense Noggin oligodeoxynucleotide administration decreases cell proliferation
      in the dentate gyrus of adult rats.
AB  - The dentate gyrus of the hippocampus is one of few regions in the adult mammalian
      brain characterized by ongoing neurogenesis. It has been demonstrated that Noggin
      antagonizes bone morphogenetic protein-4 (BMP4) to create a niche for
      subventricular zone neurogenesis. We previously demonstrated that Noggin and BMP4
      showed strong expression in the proliferative subgranular layer of the dentate
      gyrus in adult rats. To examine the action of Noggin on cell proliferation in the
      dentate gyrus of adult rats, we administered antisense oligodeoxynucleotide
      (ASODN) to Noggin by continuous infusion into the lateral ventricle of rats.
      Antisense-infused rats displayed significant reduction in number of
      bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus. This indicated that
      endogenous Noggin activity is important for naturally occurring cell
      proliferation in the dentate gyrus, and perhaps neurogenesis, and is one of the
      many factors involved in its regulation.

PMID- 15265601
TI  - Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium
      acetate (HMRlignan) in rats.
AB  - Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan
      enterolactone was evaluated in a prenatal developmental toxicity study conducted
      in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4%
      (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex
      (HMRlignan; potassium acetate level approximately 20% w/w within the preparation)
      for days 0-21 of gestation. Test substance intake was calculated to be 0.14-0.18,
      0.46-0.74, and 1.19-2.93 g/kg body weight/day for the low, mid, and high-dose
      groups, respectively. The rats were sacrificed on day 21 of the gestation period
      and examined for standard parameters of reproductive performance (fecundity
      index, gestation index, number of corpora lutea, number of implantations, pre-
      and post-implantation loss, number of early- and late resorptions, number of live
      and dead fetuses, sex-ration and the weight of the reproductive organs). The
      fetuses were examined for external, visceral, and skeletal alterations. The
      results from this study showed no effects on reproductive performance or any
      treatment related findings following external, visceral, and skeletal examination
      of the fetuses. However, approximately half of the mated dams of the high-dose
      failed to thrive due to an unexpected large decrease in their food intake, and
      were sacrificed early. Body weights of the remaining animals of the high-dose
      group were decreased. Food consumption was decreased in all treatment groups
      during the first three days of the gestation period as a result of decreased
      palatability of the feed. In conclusion, the no-observed-effect level (NOEL) for
      maternal effects was 1%, whereas the NOEL for fetal development following daily
      oral HMRlignan administration throughout the gestation was equivalent to 4% in
      the diet.

PMID- 15265602
TI  - An evaluation of benchmark dose methodology for non-cancer continuous-data health
      effects in animals due to exposures to dioxin (TCDD).
AB  - The U.S. Environmental Protection Agency (EPA) has conducted extensive reviews
      and analyses of health effects associated with exposures to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Because the
      carcinogenicity of TCDD has received considerable attention from EPA and others,
      this paper focuses on animal data for non-cancer health effects that sometimes
      appear to be almost as sensitive as cancer to TCDD exposures. Benchmark dose
      (BMD) methodology can be used to identify point-of-departure (POD) estimates for
      use in derivation of reference doses or evaluation of margins of exposure.
      However, selection of an appropriate BMD methodology for assessment of non-cancer
      data, which are usually continuous (non-quantal), needs to be considered. One
      option available for a benchmark dose is to use a small percentage change in the
      mean response relative to the estimated maximum effect of TCDD at large doses.
      The benchmark based on a change estimated to equal 1% of the estimated maximum
      change from background to the asymptotic response at large doses (denoted as the
      relative ED01) was used by EPA in a reassessment of TCDD health risks. A lower
      confidence limit (LED01) could serve as a point of departure for setting a
      reference dose (RfD). This is a somewhat arbitrary effect level, generally within
      the background range of variation among unexposed animals, with an unknown risk.
      An alternative approach is recommended in which the risk of abnormal levels can
      be estimated. For continuous-data effects, a low and/or high percentile (e.g.,
      1st and/or 99th) in unexposed control animals can be used to define abnormal (not
      necessarily adverse) levels. From a dose-response curve and the standard
      deviation, it is possible to estimate the excess risk (proportion) of animals
      with abnormal levels as a function of dose for normally distributed levels. With
      this approach, the risk-based benchmark dose (BMD01) represents the dose with an
      estimated excess risk of 1% of the animals in the abnormal range rather than an
      arbitrary change in the value of the measured endpoint. Values for the relative
      and risk-based benchmark doses are computed from published data for a variety of
      non-cancer health effects associated with exposure to TCDD. For the 30 cases
      investigated, the BMD01 tended to vary around the lowest experimental dose
      tested, whereas the relative ED01 tended to be about a factor of three below the
      lowest dose, and the BMD01 was more precisely estimated than the ED01 as
      reflected by narrower confidence intervals. The BMDL01 values were on average
      more than fivefold higher than the corresponding LED01 values. However, these
      values still provide a conservative assessment for POD assessment, because the
      BMDL01 tends to be about an order of magnitude lower (more conservative) than the
      no-observed-adverse-effect level. This analysis demonstrates the potential impact
      of alternative choices in benchmark dose methodology. In combination with
      selection of appropriate adverse health effect endpoint(s) and studies, use of
      the risk-based BMD results in identification of more valid and meaningful POD
      estimates for non-cancer effects compared to the use of the relative ED approach.

PMID- 15265603
TI  - The stability of historical control data for common neoplasms in laboratory rats:
      adrenal gland (medulla), mammary gland, liver, endocrine pancreas, and pituitary
      gland.
AB  - Time-related changes in the incidences of spontaneous neoplasms in adrenals
      (medulla), mamma, liver, pituitary, and (endocrine) pancreas were assessed
      statistically in Wistar, Sprague-Dawley, and F344 rats employed by BASF, Germany
      and major European contract research organizations over the last 20 years.
      Negative trends (7 of 80 cases) were observed for pituitary pars distalis
      adenomas in Sprague-Dawley males and females, for pancreas islet cell adenomas in
      BASF Wistar males and females, for benign adrenal pheochromocytomas in Sprague
      Dawley males, for malignant pheochromocytomas in F344 males, and for mammary
      gland fibroadenomas in BASF Wistar females. Positive trends (13 of 80 cases) were
      observed for benign pheochromocytomas, mammary gland adenocarcinomas, and
      pancreas islet cell carcinomas in HanWistar females, for malignant
      pheochromocytomas and islet cell carcinomas in BASF Wistar males, for benign
      pheochromocytomas and islet cell adenomas in F344 males, for mammary gland
      fibroadenomas in Sprague-Dawley females, and for benign hepatocellular tumors in
      HanWistar males and females, and in BASF Wistar and Sprague-Dawley females. In 60
      of 80 cases there were no statistically significant trends. These results
      indicate that the majority of tumor types showed no time trends and that, in each
      rat strain, certain tumor types are susceptible to slight positive or negative
      time trends. Accordingly, the validity and use of historical control data should
      be based on an organ- and strain-specific statistical analysis of tumor incidence
      over time.

PMID- 15265604
TI  - Carbon black should not be classified as a human carcinogen based on rodent
      bioassay data.
AB  - Numerous epidemiology studies have failed to adequately demonstrate an increased
      risk of lung cancer due to occupational exposure to carbon black (CB). CB is not
      carcinogenic to mice (oral, skin or inhalation), hamsters (inhalation or
      intratracheal), guinea pigs (inhalation), rabbits (skin or inhalation), primates
      (skin or inhalation) or rats (oral). Only studies conducted by inhalation and
      intratracheal administration in rats have shown significant increases in benign
      and malignant lung tumors and lesions described as benign cystic keratinizing
      squamous-cell (KSC) tumors. CB-induced lung tumor formation, including KSC
      lesions, occurs only in rats. An expert panel reviewing KSC lesions (induced in
      rats by TiO2 or p-aramid) concluded that KSC lesions are not seen in humans. Lung
      tumors in humans are primarily located in the bronchial airways, whereas in the
      rat they occur in the parenchyma and are alveolar in origin. This species
      specific response (tumor formation and KSC lesions) by the rat to CB, not seen in
      any other laboratory species and which has not been reported in humans, strongly
      suggests that the results of the rat inhalation bioassay should not be considered
      directly relevant when assessing human risk. Therefore, CB should not be
      classified as carcinogenic to humans based on the rodent bioassay data.

PMID- 15265605
TI  - Development of an oral cancer slope factor for Aroclor 1268.
AB  - Rodent cancer bioassays indicate that substantial differences exist among PCB
      mixtures in terms of tumorigenic response, although no bioassay has been
      conducted with Aroclor 1268. The USEPA has used data from these studies to
      develop three sets of PCB cancer slope factors (CSFs) ranging from 0.07 to
      2.0(mg/kg-day)(-1). Selection of the appropriate CSF for risk assessment purposes
      is largely a function of the exposure circumstances rather than the PCB mixture
      involved. Since the congener composition of Aroclor 1268 differs substantially
      from that of the predominant PCB mixture (Aroclor 1254) used to derive the CSFs,
      the validity of applying existing CSFs to Aroclor 1268 is questionable. We have
      therefore undertaken the task of developing cancer potency estimates specifically
      for Aroclor 1268. Potency estimation approaches for Aroclor 1268 were based in
      part on existing potency estimates for other PCB mixtures, coupled with the
      relative 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQ) content and
      bioaccumulation potential of PCB mixtures. As such, both Ah-dependent and
      independent mechanisms of tumorigenesis were considered relevant. Both empirical
      evidence and mechanistic considerations indicate Aroclor 1268 is substantially
      less toxic and carcinogenic than the PCB mixtures that have been used by the
      USEPA to develop CSFs. The present analysis indicates that Aroclor 1268 is likely
      to be 1-2 orders of magnitude less potent than Aroclor 1254 in terms of potential
      tumorigenicity. Therefore, we suggest an upper-bound cancer potency factor of
      0.27(mg/kg-day)(-1) for Aroclor 1268, a value that is 7- to 8-fold lower than the
      USEPA's current default, but nonetheless adequately conservative.

PMID- 15265606
TI  - Approaches to carcinogenic risk assessment for polycyclic aromatic hydrocarbons:
      a UK perspective.
AB  - This paper reviews the approaches to carcinogenic risk assessment of polycyclic
      aromatic hydrocarbons (PAHs) in air pollution with emphasis on high potency PAHs
      such as dibenzo[a,l]pyrene (DB[a,l]P). The potency of DB[a,l]P may be 100-fold
      greater than benzo[a]pyrene (B[a]P); thus the B[a]P surrogate approach currently
      used to monitor for compliance with UK air pollution standards may not be
      appropriate. It is suggested that an approach based on potency equivalency
      factors (PEFs) could be developed to include highly potent PAHs provided an
      appropriate reference data set for relevant PAHs using a route acceptable for
      inhalation risk assessment is selected. Available data suggest that intratracheal
      administration of low doses of PAHs to rats is likely to simulate the kinetics of
      inhalation exposure to PAHs in a feasible manner. The use of a measure of total
      DNA adducts as an endpoint, which correlates well with lung tumourigenicity,
      would provide surrogate data for setting PEFs without the need for long-term
      bioassays in rodents. Further, dose-response studies using intratracheal
      administration of a range of PAHs singly and in combination to assess additivity
      are required to develop a PEF system for inhalation PEFs derived from DNA adduct
      measurements.

PMID- 15265607
TI  - A hematology surveillance study of petrochemical workers exposed to benzene.
AB  - Historically, complete blood counts (CBCs) have been recognized as an easy and
      readily available screen for hematotoxicity following occupational exposure to
      benzene. The purpose of this study is to evaluate hematology data from employees
      who have ever participated in the Shell Benzene Medical Surveillance Program
      (BMSP) compared to employees who have not participated and to examine the
      sensitivity of CBCs to detect hematological changes in a low-exposure
      occupational setting. This large study included 1200 employees who participated
      in the BMSP, with mean benzene exposure (TWA-8) of 0.60 ppm from 1977 to 1988 and
      0.14 ppm since 1988, and 3227 comparison employees. The comparison group included
      employees not enrolled in either the benzene or butadiene surveillance programs.
      Abnormality of six CBC parameters and the adjusted mean values of these
      parameters in the exposed group were compared with that of the comparison group.
      We found no increased abnormality for any hematology parameter among exposed
      employees. The adjusted mean values (adjusted for age, sex, race, length of time
      between first and last exam, and current smoking status) of the exposed employees
      were similar to those in the comparison group. At current occupational exposure
      levels for benzene, no evidence of adverse hematological effects was observed in
      this study. These results raise the question of whether annual CBC surveillance
      for benzene-exposed workers has adequate sensitivity to detect meaningful
      hematological changes due to low-level exposures.

PMID- 15265608
TI  - Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in
      rats.
AB  - The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was
      examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of
      0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of
      gestation. At Cesarean section 25, 22, 23, and 23 rats were found to be pregnant
      in the control, low-, mid-, and high-dose group, respectively. The NHDC treatment
      was well tolerated and all animals survived till the end of the study. Body
      weights (bw) and body weight gains did not differ between controls and NHDC
      treatment groups. The intake of NHDC was 0.8-0.9, 1.6-1.7, and 3.1-3.4 g/kg
      bw/day for the low-, mid-, and high-dose group, respectively. Except for cecal
      enlargement, there were no changes observed at necropsy which could be related to
      the NHDC treatment. All dams had viable fetuses. The fecundity and gestation
      index, the number of corpora lutea, implantation sites, live and dead fetuses,
      early and late resorptions, pre- and post-implantation losses, and sex-ratio were
      not affected by the treatment. There were no differences for the mean weight of
      the gravid and empty uterus, ovaries, and placenta between the NHDC treatment
      groups and the controls. Examination of the fetuses for external, visceral, and
      skeletal changes did not reveal any fetotoxic, embryotoxic or teratogenic effects
      of NHDC. In conclusion, no adverse effects were observed at NHDC levels of up to
      5% of the diet, the highest dose level tested, at which the rats consumed about
      3.3g/kg body weight/day. The observed cecal enlargement is a well-known
      physiological, adaptive response to the ingestion of high doses of a low
      digestible substance and is generally accepted to lack toxicological relevance.

PMID- 15265609
TI  - Preface. Cyclodextrins.

PMID- 15265610
TI  - Safety assessment of gamma-cyclodextrin.
AB  - Gamma-cyclodextrin (gamma-CD) is a cyclic alpha-(1,4)-linked oligosaccharide
      consisting of eight glucose molecules. Like other cyclodextrins, gamma-CD can
      form inclusion complexes with a variety of organic molecules because the inner
      side of the torus-like molecule is less polar than the outer side. In foods,
      gamma-CD may be used as a carrier for flavors, vitamins, polyunsaturated fatty
      acids, and other ingredients. It also has useful properties as a stabilizer in
      different food systems. The daily intake from all its intended uses in food at
      highest feasible concentrations has been estimated at 4.1g/person/day for
      consumers of gamma-CD containing foods. The present review summarizes the safety
      data of gamma-CD. The toxicity studies consist of standard genotoxicity tests,
      subchronic rat studies with oral and intravenous administration of gamma-CD for
      up to 3 months, a subchronic (3-month) toxicity study in dogs, a (1-year) oral
      toxicity study in rats, and embryotoxicity/teratogenicity studies in rats and
      rabbits. In the studies with oral administration, gamma-CD was given at dietary
      concentrations of up to 20%. All these studies demonstrated that gamma-CD is well
      tolerated and elicits no toxicological effects. Metabolic studies in rats showed
      that gamma-CD is rapidly and essentially completely digested by salivary and
      pancreatic amylase. Therefore, the metabolism of gamma-CD closely resembles that
      of starch and linear dextrins. A human study with ingestion of single doses of 8
      g gamma-CD or 8 g maltodextrin did not reveal a difference in gastrointestinal
      tolerance of these two products. An interaction of ingested gamma-CD with the
      absorption of fat-soluble vitamins or other lipophilic nutrients is not to be
      expected because the formation of inclusion complexes is a reversible process,
      gamma-CD is readily digested in the small intestine, and studies with beta-CD, a
      non-digestible cyclodextrin, have shown that the bioavailability of vitamins (A,
      D, and E) is not impaired. On basis of these studies it is concluded that gamma
      CD is generally recognized as safe (GRAS) for its intended uses in food.

PMID- 15265611
TI  - Subchronic oral toxicity studies with alpha-cyclodextrin in rats.
AB  - The toxicity of alpha-cyclodextrin (alpha-CD), a cyclic polymer of six alpha-1,4
      linked glucopyranosyl units with potential applications as a food ingredient,
      more specifically a water-soluble dietary fiber, was examined in a 4-week range
      finding study and a 13-week oral toxicity study in rats. In the 4-week study, the
      test substance was administered to groups of Bor:WISW(SPF;Cpb) rats at dietary
      levels of 0, 1, 5, and 15% (5 rats/sex/group). An additional group received a
      diet with 5% beta-CD. In the 13-week study, groups of Crl:(WI)WU Br rats received
      diets with 0, 1.5, 5, or 20% alpha-CD. An additional group received a diet with
      20% lactose (20 rats/sex/group). Satellite groups of 10 rats/sex were attached to
      the control, 20% alpha-CD and 20% lactose group. Following the 13-week treatment
      period, these satellite groups were kept on a standard, cereal-based rodent diet
      for a 4-week recovery period. Parameters measured during the two studies included
      clinical signs, body weights, food and water intake, hematological and
      clinicochemical parameters, and organ weights as well as gross and
      histopathological observations at necropsy. In the 13-week study, ophthalmoscopic
      examinations as well as urine and feces analyses were also conducted. There were
      no treatment-related mortalities in either study. In the 4-week study, persistent
      diarrhea was the most prominent, treatment-related effect observed in the animals
      of the 15% alpha-CD group especially in the male animals. In association with
      this effect, food consumption and food conversion efficiency were decreased. In
      line with observations from studies with other low-digestible, yet fermentable
      carbohydrates, the weight of the full and empty cecum was increased significantly
      in the 5% alpha-CD, 5% beta-CD, and 15% alpha-CD group. The reduced relative
      liver weights (in males and females) and the significantly increased relative
      testes weight which were observed in the 15% alpha-CD group, were attributed to
      the impaired nutritional condition (due to diarrhea) and the reduced body weight
      of the animals of this group, respectively. Microscopic examination of the main
      organs did not reveal pathological alterations that could be attributed to the
      alpha-CD treatment. In the 13-week study, soft stool and infrequent mild diarrhea
      were observed only during the first 2-3 weeks in the 20% alpha-CD and 20% lactose
      group (mainly male animals). Accordingly, body weights were reduced in males of
      the 20% lactose group throughout the study and in the 20% alpha-CD group during
      the last week of the study. Food intakes were slightly increased in the 20% alpha
      CD group and the food conversion efficiency, was significantly reduced in males,
      but not females, of the 20% alpha-CD and 20% lactose group. There were no
      treatment-related changes of hematological parameters. In line with similar
      observations from studies on other low-digestible carbohydrates, the urinary pH
      was decreased and urinary calcium levels increased in the 20% alpha-CD and 20%
      lactose group. Similarly, the fecal dry weight and nitrogen output was increased
      in these groups. At termination of the treatment, significantly in creased cecum
      weights (full and empty) were observed in the 5 and 20% alpha-CD groups and the
      20% lactose group. The relative (not absolute) weight of the spleen was
      significantly increased in males of the 20% alpha-CD group. In the 20% lactose
      group, the relative weights of the spleen and liver (females) and the testes,
      brain, and adrenals (males) were significantly increased. The histopathological
      examination of these and all other organs and tissues did not reveal any
      abnormalities that could be attributed to the alpha-CD or lactose treatment. In
      conclusion, the ingestion of alpha-CD for 13-weeks at dietary levels of up to 20%
      (corresponding to intakes of 12.6 and 13.9 g/kg bodyweight/d in male and female
      rats, respectively) did not produce any signs of toxicity or adverse effects.

PMID- 15265612
TI  - Subchronic (13-week) oral toxicity study of alpha-cyclodextrin in dogs.
AB  - The oral toxicity of alpha-cyclodextrin (alpha-CD) was examined in a 13-week
      feeding study in which groups of Beagle dogs received alpha-CD in the diet at
      concentrations of 0 (control), 5, 10, or 20% (4 dogs/sex/group). No treatment
      related changes were noted in behavior or appearance of the dogs and no
      mortalities occurred. Diarrhea occurred in all alpha-CD groups. The incidence and
      severity of diarrhea increased with increasing dietary levels of alpha-CD and was
      more pronounced in males than females. Nonetheless, all dogs remained in good
      health and gained weight. Food intake was slightly increased and food efficiency
      was slightly decreased in the 20% alpha-CD group. However, these changes did not
      reach statistical significance. No treatment-related differences were observed
      with respect to ophthalmoscopic examinations, hematological parameters,
      clinicochemical analyses of the plasma, and semiquantitative urine analyses. Only
      the urinary pH was slightly below control levels in males (p > 0.05) and females
      (p < 0.05) of the 20% alpha-CD group. No abnormalities were seen at necropsy that
      could be attributed to the treatment. The organ weight data revealed cecal
      enlargement in the 10 and 20% alpha-CD groups (significant only in males). The
      relative weight of the colon was also slightly increased in the 10 and 20% alpha
      CD groups (significant only in females of the 10% alpha-CD group). On microscopic
      examination, no treatment-related alterations were observed in any of the various
      organs and tissues. In conclusion, transient diarrhoea, enlargement of the cecum
      and colon and a slightly increased acidity of the urine were the only treatment
      related effects. These changes are well-known physiological responses to the
      presence of high amounts of not digested, fermentable carbohydrates in the lower
      gut. They are known to be reversible on cessation of the treatment and are not
      associated with histological alterations of the intestinal tissues. It is
      concluded, therefore, that the high dose level, at which the male and female dogs
      consumed about 9.8 and 10.4 g alpha-CD/kg bw/d, respectively, is the NOAEL of
      this 13-week toxicity study.

PMID- 15265613
TI  - Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rats.
AB  - The embryotoxicity/teratogenicity of alpha-cyclodextrin (alpha-CD) was examined
      in Wistar Crl:(WI)WU BR rats. alpha-CD was fed at dietary concentrations of 0,
      1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of
      gestation. An additional group received a diet with 20% lactose. The additions to
      the diet of alpha-CD and lactose were made at the expense of pregelatinized
      potato starch. Body weight as well as food and water intake were recorded during
      the treatment period. The rats were killed on day 21 and examined for standard
      parameters of maternal reproductive performance. The fetuses were examined for
      external abnormalities, body weight and crown rump length. Fetuses were examined
      for skeletal and visceral abnormalities. Generally, alpha-CD was well tolerated
      and no deaths occurred in any group. Weight gain and food consumption were
      similar in all groups during gestation, except for a slightly yet significantly
      increased food intake in the 20% alpha-CD group from day 6 to 21. Water intake
      was similar in all alpha-CD groups; in the lactose group, it was significantly
      higher than in the controls. Maternal reproductive performance was not affected
      by the alpha-CD treatment. Examination of the fetuses for external, visceral and
      skeletal changes did not reveal any fetotoxic, embryotoxic, or teratogenic
      effects of alpha-CD. In conclusion, no adverse effects were observed at alpha-CD
      intakes of up to 20% of the diet, the highest dose level tested at which the rats
      consumed about 13 g/kg bw/day.

PMID- 15265614
TI  - Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rabbits.
AB  - In a standard embryotoxicity/teratogenicity study, alpha-cyclodextrin (alpha-CD)
      was administered to groups of sixteen, artificially inseminated New Zealand White
      rabbits at dietary concentrations of 0, 5, 10, or 20%. An additional group
      received a diet containing 20% lactose. Treatment started on day 0 of gestation
      and ended on day 29 when the animals were killed. Except for the occurrence of
      transient diarrhoea in one rabbit of the 20% alpha-CD group for a few days, the
      treatment was well tolerated. A reduced food intake in the 20% alpha-CD group
      during the first week of treatment resulted in a reduced weight gain from day 0
      to 12 of the study. However, the difference to the controls was not significant
      and at termination of the study body weights were similar in all groups. Even at
      the highest dose level, which corresponds to an intake of 5.9-7.5 g/kg bw/day, no
      signs of maternal toxicity were observed. Maternal reproductive performance was
      not affected by the treatment. Uterine weight, placental weight, fetal weight,
      number of fetuses, sex ratio, number of implanation sites, resorptions, and
      corpora lutea did not differ among the groups. Visceral and skeletal examinations
      of the fetuses did not reveal any malformations, anomalies or variations that
      could be attributed to treatment. It was concluded that dietary alpha-CD is
      generally well tolerated by pregnant rabbits, has no adverse effect on maternal
      reproductive performance and is not embryotoxic, fetotoxic, or teratogenic at
      dietary concentrations of up to 20%, the highest dose level tested.

PMID- 15265615
TI  - Safety evaluation of an alpha-cyclodextrin glycosyltranferase preparation.
AB  - Alpha-cyclodextrin glucosyltransferase (alpha-CGTase, EC 2.4.1.19) is an
      amylolytic enzyme used for the production of alpha-cyclodextrin (alpha-CD), a
      novel, soluble dietary fiber, from food-grade starch. The safety of an alpha
      CGTase preparation obtained by batch fermentation from a recombinant strain of
      Escherichia coli K12 harboring the alpha-CGTase gene from Klebsiella oxytoca
      strain M5a1 was examined. In a 13-week subchronic toxicity study in rats, the
      administration by gavage of the alpha-CGTase preparation at levels of up to 20
      ml/kg bw/day, corresponding to a total organic solids dosage of 260 mg/kg bw/day,
      did not cause any systemic toxic effect. Some signs of irritation were observed
      in the respiratory tract which occurred, however, in one sex only and/or were not
      dose-related. Accordingly, these changes were considered to be an unspecific
      consequence of the reflux and aspiration of the dosing solution. There was no
      evidence of a genotoxic activity in Ames tests and a chromosome aberration test
      in cultured human lymphocytes. It is concluded that the examined alpha-CGTase
      preparation is safe when used for the production of alpha-CD.

PMID- 15265616
TI  - Disposition of 14C-alpha-cyclodextrin in germ-free and conventional rats.
AB  - The absorption, disposition, metabolism, and excretion of uniformly (14)C-labeled
      alpha-cyclodextrin ((14)C-alpha-CD) was examined in four separate experiments
      with Wistar rats. In Experiment 1, (14)C-alpha-CD (25 microCi, 50 mg/kg bw) was
      administered intravenously to four male and four female conventional rats. In
      Experiment 2, (14)C-alpha-CD (25 microCi, 200 mg/kg bw) was given by gavage to
      four male and four female germ-free rats. In Experiments 3 and 4, (14)C-alpha-CD
      was given to groups of four male and four female conventional rats by gavage at
      different dose levels (100 microCi, 200 mg/kg bw; 25 microCi, 200 and 100 mg/kg
      bw). In all experiments, (14)C was measured in respiratory CO(2), urine, and
      feces over periods of 24-48 h, and in the contents of the gastrointestinal tract,
      blood, main organs, and residual carcass at termination of the experiments. The
      chemical identity of the (14)C-labeled compounds was examined by HPLC in blood
      (Experiment 1), urine (Experiments 1-4), feces (Experiments 2-4), and samples of
      intestinal contents (Experiments 2 and 4). Recovered (14)C was expressed as
      percentage of the administered dose. Experiment 1 showed that intravenously
      administered alpha-CD is excreted rapidly with urine. During the first 2h after
      dosing, plasma (14)C levels decreased rapidly (t(1/2), 26 and 21 min in male and
      female rats, respectively). About 13% of the administered (14)C dose (range 4.6
      30.6) was detected in the feces, respiratory CO(2), organs, and carcass at the
      end of the experiment, i.e., 24 h after dosing. The presence of about 1.9% in the
      intestinal contents and feces suggests that a certain fraction of systemic alpha
      CD is eliminated with the bile or saliva. Conclusive evidence, either positive or
      negative, for a hydrolysis and further metabolism of a small fraction of the
      administered alpha-CD by the enzymes of the mammalian body could not be gained
      from this experiment. Upon oral administration of (14)C-alpha-CD to germ-free
      rats (Experiment 2), about 1.3% of the label expired as CO(2) within 24 h. In the
      urine collected from 0 to 8 h after dosing, (14)C-alpha-CD was the only
      radiolabeled compound detected. The amounts of alpha-CD detected in the urine
      suggest that on average about 1% of an oral dose is absorbed in rats during small
      intestinal passage. In conventional rats (Experiments 3 and 4), a delayed
      appearance of respiratory (14)CO(2) was observed which is attributed to the non
      digestibility of alpha-CD and its subsequent microbial fermentation in the cecum
      and colon. In the urine collected at 4 h after dosing, a small amount of
      unchanged (14)C-alpha-CD was detected which confirms that about 1% of the
      ingested alpha-CD is absorbed intact and is excreted via the kidneys. No (14)C
      alpha-CD was found in the feces. It is concluded from the data that ingested
      (14)C-alpha-CD is not digested in the small intestine of rats but is fermented
      completely by the intestinal microbiota to absorbable short-chain fatty acids.
      Therefore, the metabolism of alpha-CD resembles closely that of resistant starch
      or other fermentable dietary fibers.

PMID- 15265617
TI  - Modeling fibrin aggregation in blood flow with discrete-particles.
AB  - Excessive clotting can cause bleeding over a vast capillary area. We study the
      mesoscopic dynamics of clotting by using the fluid particle model. We assume that
      the plasma consists of fluid particles containing fibrin monomers, while the red
      blood cells and capillary walls are modeled with elastic mesh of "solid"
      particles. The fluid particles interact with each other with a short-ranged,
      repulsive dissipative force. The particles containing fibrin monomers have a dual
      character. The polymerization of fibrin monomers into hydrated fibrins is modeled
      by the change of the interactions between fluid particles from repulsive to
      attractive forces. This process occurs with a probability being an increasing
      function of the local density. We study the blood flow in microscopic capillary
      vessels about 100 microm long and with diameters in order of 10 microm. We show
      that the model of polymerization reflects clearly the role played by fibrins in
      clotting. Due to the density fluctuations caused the by the high acceleration,
      the fibrin chains are produced within a very short time (0.5 ms). Fibrin
      aggregation modifies the rheological properties of blood, slows down the
      incipient flow, and entraps the red blood cells, thus forming dangerous clots.

PMID- 15265618
TI  - Regression models for unbalanced longitudinal ordinal data: computer software and
      a simulation study.
AB  - A computer program GGOREX in the form of a SAS macro is developed for the
      analysis of longitudinal ordinal data. It is extended from GEECAT and GEEGOR
      developed by Williamson, Lipsitz and Kim in their paper in 1999. An illustrative
      example with some preliminary data from a study conducted by the National
      Institute of Child Health and Human Development and the University of Alabama at
      Birmingham is given. Another set of computer programs is developed to make it
      possible to conduct a simulation study to validate the GGOREX procedure in a
      finite sample. A simple computer program in FORTRAN using the IMSL software
      library is developed to solve for the probability distribution of the
      longitudinal ordinal responses according to the correlation specification.

PMID- 15265619
TI  - Computer program for determining fluorescence resonance energy transfer
      efficiency from flow cytometric data on a cell-by-cell basis.
AB  - The determination of fluorescence resonance energy transfer (FRET) with flow
      cytometry (FCET) is one of the most efficient tools to study the proximity
      relationships of cell membrane components in cell populations on a cell-by-cell
      basis. Because of the high amount of data and the relatively tedious
      calculations, this procedure should be assisted by powerful data processing
      software. The currently available programs are not able to fulfill this
      requirement. We developed a Windows-based program to calculate fluorescence
      resonance energy transfer efficiency values from list mode flow cytometry
      standard (FCS) files. This program displays the measured data in standard plots
      by generating one- and two-parameter histograms on linear or logarithmic scales.
      A graphical gating tool allows the user to select the desired cell population
      according to any combination of the parameter values. The program performs
      several statistical calculations, including mean, S.D., percent of the gated
      data. We have implemented two types of data sheet for FRET calculations to aid
      and guide the user during the analysis: one with population-mean-based
      autofluorescence correction and the other with spectrum-based cell-by-cell
      autofluorescence correction. In this paper, we describe the gating algorithms,
      the file opening procedure and the rules of gating. The structure of the program
      and a short description of the graphical user-interface (GUI) are also presented
      in this article.

PMID- 15265620
TI  - JIDE: a new software for computer-aided design of hip prosthesis.
AB  - This work is aimed at developing an innovative simulation environment supporting
      and improving the design of standard joint implants (JPD integrated design
      environment (JIDE)). The conceptual workflow starts from the design of a new
      implant, by using conventional CAD programmes and completes with the generation
      of a report that summarises the goodness for a new implant against a database of
      human bone anatomies. For each dataset in the database, the JPD application
      calculates a set of quantitative indicators that will support the designer in the
      evaluation of its design on a statistical basis. The resulting system is thus
      directed to prostheses manufacturers and addresses a market segment that appears
      to have a steady growth in the future.

PMID- 15265621
TI  - Design and implementation of a web-enabled haematological system.
AB  - This paper describes the design and the implementation of a web-enabled
      integrated haematological system, named e-HS. The proposed system runs on a set
      of distributed network nodes providing useful haematological services. These
      services include patient-oriented data management, digitized histopathological
      slides (DHS) acquisition, teleconsulting facilities, etc. The objective of e-HS
      is to supply web-enabled services according to haematological requirements,
      implement a distributed storage scheme for DHS, and provide a common database
      containing all haematological laboratory results by using eXtensible Markup
      Language (XML) and web technologies. Our implementation can be accessible to
      every authorized physician at the distributed nodes without any additional
      software. The only software required for the user is the widely used browser
      (e.g. MS Internet Explorer v 3.02 or higher). Besides, by using a self-explaining
      user interfaces and HTML-techniques, such as hyperlinks, the necessary amount of
      training at the physicians-side is reduced to a minimum. A first implementation
      of the e-HS, has been established at the Medical Physics Department of the
      University of Patras (master node of the system), and has been tested with
      success by the medical staff of the Hospital Departments of the University of
      Patras and Thessalonica that served as distributed nodes of the system.

PMID- 15265622
TI  - Semia: semi-automatic interactive graphic editing tool to annotate ambulatory ECG
      records.
AB  - We designed and developed a special purpose interactive graphic editing tool semi
      automatic (Semia) to annotate transient ischaemic ST segment episodes and other
      non-ischaemic ST segment events in 24h ambulatory electrocardiogram (ECG)
      records. The tool allows representation and viewing of the data, interaction with
      the data globally and locally at different resolutions, examining data at any
      point, manual adjustment of heart-beat fiducial points, and manual and automatic
      editing of annotations. Efficient and fast display of ambulatory ECG signal
      waveforms, display of diagnostic and morphology feature-vector time-series,
      dynamic interface controls, and automated procedures to help annotate, made the
      tool efficient, user friendly and usable. Human expert annotators used the Semia
      tool to successfully annotate the Long-Term ST database (LTST DB), a result of a
      multinational effort. The tool supported paperless editing of annotations at
      dislocated geographical sites. We present design, characteristic "look and feel",
      functionality, and development of Semia annotating tool.

PMID- 15265623
TI  - Simulation of emission tomography using grid middleware for distributed
      computing.
AB  - SimSET is Monte Carlo simulation software for emission tomography. This paper
      describes a simple but effective scheme for parallel execution of SimSET using
      NetSolve, a client-server system for distributed computation. NetSolve (version
      1.4.1) is "grid middleware" which enables a user (the client) to run specific
      computations remotely and simultaneously on a grid of networked computers (the
      servers). Since the servers do not have to be identical machines, computation may
      take place in a heterogeneous environment. To take advantage of diversity in
      machines and their workloads, a client-side scheduler was implemented for the
      Monte Carlo simulation. The scheduler partitions the total decay events by taking
      into account the inherent compute-speeds and recent average workloads, i.e., the
      scheduler assigns more decay events to processors expected to give faster service
      and fewer decay events to those expected to give slower service. When compute
      speeds and sustained workloads are taken into account, the speed-up is
      essentially linear in the number of equivalent "maximum-service" processors. One
      modification in the SimSET code (version 2.6.2.3) was made to ensure that the
      total number of decay events specified by the user is maintained in the
      distributed simulation. No other modifications in the standard SimSET code were
      made. Each processor runs complete SimSET code for its assignment of decay
      events, independently of others running simultaneously. Empirical results are
      reported for simulation of a clinical-quality lung perfusion study.

PMID- 15265624
TI  - Web-based delivery of medical multimedia contents using an MPEG-4 system.
AB  - Moving picture expert group compression standard version 4 (MPEG-4) is a standard
      for video coding aimed at multimedia applications. MPEG-4 was developed to enable
      high compression rate in a low bitrate transmission via the Internet or mobile
      telecommunications. Although these characteristics of MPEG-4 are suitable for
      telemedicine, little is known about the possibility of using this technology in
      the field of telemedicine. We evaluated the quality of MPEG-4-encoded medical
      video streams and compared them with original analogue videos and audio-video
      interleave (AVI) files. Although MPEG-4 video streams have the advantage of small
      file size, they were found to be inferior to original videos and AVI files in
      terms of smoothness of motion pictures, sharpness of images and clearness of
      sound. Illegibility of characters was a major problem in MPEG-4 files. The score
      for total impression of MPEG-4 files was significantly lower than those for AVI
      files. The results of this study suggest that the quality of MPEG-4-encoded video
      streams is not adequate for telemedicine.

PMID- 15265625
TI  - Co-regulation of female sexual behavior and pregnancy induction: an exploratory
      synthesis.
AB  - This paper will review both new and old data that address the question of whether
      brain mechanisms involved in reproductive function act in a coordinated way to
      control female sexual behavior and the induction of pregnancy/pseudopregnancy
      (P/PSP) by vaginocervical stimulation. Although it is clear that female sexual
      behavior, including pacing behavior, is important for induction of P/PSP, there
      has been no concerted effort to examine whether or how common mechanisms may
      control both functions. Because initiation of P/PSP requires that the female
      receive vaginocervical stimulation, central mechanisms controlling P/PSP may be
      modulated by or interactive with those that control female sexual behavior. This
      paper presents a synthesis of the literature and recent data from our lab for the
      purpose of examining whether there are interactions between behavioral and
      neuroendocrine mechanisms which reciprocally influence both reproductive
      functions.

PMID- 15265626
TI  - Sensitization and dishabituation of swim induction in the leech Hirudo
      medicinalis: role of serotonin and cyclic AMP.
AB  - In this paper the role of serotonin (5HT) and cyclic AMP (cAMP) in sensitization
      and dishabituation of swim induction (SI) has been investigated in the leech
      Hirudo medicinalis. Electrical stimulation of the body wall evokes swimming
      activity with a constant latency. In animals with a disconnection between head
      ganglion and segmental ganglia, repetitive stimulation induces habituation of
      swimming whereas brushing on the dorsal skin provokes sensitization of a naive
      response or dishabituation of a previously habituated response. Our findings
      indicate that 5HT is the neurotransmitter underlying both sensitization and
      dishabituation of SI. Injection of the 5HT receptor blocking agent methysergide
      impaires the onset of sensitization and dishabituation induced by brushing.
      Moreover, injection of 5HT mimics these forms of nonassociative learning, whereas
      injection of dopamine does not. Finally, the effects of 5HT are mediated by cAMP:
      (1) after injections of specific adenylate cyclase inhibitors such as MDL 12.330A
      or SQ22536, brushing becomes ineffective in facilitating the SI in either non
      habituated or habituated animals. (2) 8Br-cAMP application mimics both
      sensitization and dishabituation of SI.

PMID- 15265627
TI  - Effects of post-session injections of anisomycin on the extinction of a spatial
      preference and on the acquisition of a spatial reversal preference.
AB  - Four experiments with C57BL/6 mice examined the effects of protein synthesis
      inhibition on extinction of spatial preferences in the Morris water maze. The
      protein synthesis inhibitor anisomycin was injected systemically immediately
      after spatial reversal sessions, which consisted of eight, two, or one reversal
      trials. Anisomycin had no effect on extinction of a spatial preference with eight
      reversal trials per session. When only two reversal trials were administered per
      session, anisomycin slowed extinction initially, although full extinction
      occurred with further training even in the presence of anisomycin. In both cases,
      anisomycin blocked acquisition of the reversal preference. When anisomycin
      injections followed a single simple extinction trial, performance was not
      disrupted. These findings suggest that acquisition and extinction may involve
      different molecular processes, and they do not support the idea that brief
      extinction trials induce a protein synthesis-dependent reconsolidation phase of
      spatial memory.

PMID- 15265628
TI  - Involvement of nitric oxide-dependent pathways of dorsolateral periaqueductal
      gray in the effects of ethanol in rats submitted to the elevated plus-maze test.
AB  - Our previous study showed the microinjection of drugs that influence the nitric
      oxide (NO)-mediated neurotransmission in the hippocampus impacts upon the
      anxiolytic-like effect of ethanol. In this study, we examined whether NO
      dependent pathways of the dorsolateral periaqueductal gray (dlPAG) participate in
      the anxiolytic effect of ethanol in rats submitted to the elevated plus-maze
      test. We evaluated the impact on ethanol effects of the nitric oxide synthase
      (NOS) inhibitor 7-nitroindazole, the soluble guanylate cyclase inhibitor 1H
      (1,2,4)-oxodiazolo (4,3-a) quinoxalin-1-one (ODQ), the cyclic guanylate
      monophosphate (cGMP) analogue 8-bromo-cGMP and the NO donor sodium nitroprusside.
      The results showed that ODQ and 7-nitroindazole increased the percentage of open
      arm entries and of time spent on open arms in the elevated plus maze in rats
      injected with ethanol at 1.0g/kg, a dose that did not produce anxiolysis per se.
      Conversely, 8-bromo-cGMP and sodium nitroprusside blocked the increased
      exploration of open arms exhibited by rats treated with a higher dose of ethanol
      (1.2g/kg). Taken together, the results suggest that the inhibition of NO
      dependent pathways of the dlPAG enhances the anxiolytic effect of ethanol,
      whereas the activation of these pathways results in an opposite effect.

PMID- 15265629
TI  - Proinflammatory cytokines differentially affect leverpress avoidance acquisition
      in rats.
AB  - Recent evidence indicates that the pro-inflammatory cytokines (PICs) can affect
      learning and memory processes. To examine the effect of the PICs on leverpress
      escape/avoidance conditioning, we injected male Sprague-Dawley rats with IL
      1beta, IL-6 (both 3.0 microg/kg, i.p.), TNFalpha (6.0 microg/kg, i.p.) or
      vehicle, 24h before a single 4-h session of leverpress escape/avoidance
      conditioning. The TNFalpha-treated animals made more avoidance responses and
      fewer escape responses than controls during the last hour of the session.
      Further, both TNFalpha- and IL-1beta-treated animals had a higher percent
      avoidance than controls during the 4th hour of the session. None of the cytokines
      had an effect on the number of leverpresses during safety, a putative measure of
      anxiety. Results are discussed in terms of the differential central effects of
      the pro-inflammatory cytokines and the possible relationship to avoidance
      conditioning.

PMID- 15265630
TI  - Insular cortex lesions alter conditioned taste avoidance in rats differentially
      when using two methods of sucrose delivery.
AB  - The insular gustatory cortex may be essential for the evaluation of saliency and
      representation of the incentive values of tastes. Gustatory cortex lesions should
      interfere with conditioned taste avoidance according to these factors, which
      depend on the conditioned taste avoidance protocol used. The present study was
      aimed at investigating the effects of bilateral lesions of the gustatory cortex
      focusing on electrolytic and excitotoxic lesions. Lesioned and sham-operated male
      Long-Evans rats were intoxicated using LiCl after drinking sucrose from a tube
      (SD) or having the same amount of sucrose fed directly into their mouths through
      a chronically implanted intra-oral (IO) cannula. Every aspect of the experiment
      was carefully counterbalanced between the experimental groups. In the control
      groups, the acquired avoidance towards sucrose was strongly preserved over eight
      extinction test days in SD rats but not in IO rats, in which a progressive
      decline was recorded. Electrolytic gustatory cortex lesions impaired but did not
      suppress conditioned taste avoidance in both protocols. Excitotoxic lesions tend
      to impair CTA also, but differentially according to the SD or IO protocols.
      Extinction of CTA was selectively impaired in the SD protocol by small lesions
      destroying the anterior insular cortex.

PMID- 15265631
TI  - Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist
      administration.
AB  - The early postnatal brain development, when many potentially sensitive processes
      occur, has been shown to be vulnerable to different pharmacological and
      environmental compounds. In the present investigation, four groups of neonatal
      NMRI male mice were administered the glutamate NMDA receptor antagonist ketamine
      (50 mg/kg, s.c.), or the GABA(A) receptor agonist diazepam (5 mg/kg, s.c.), or co
      administered ketamine (50 mg/kg, s.c.) and diazepam (5 mg/kg, s.c.), or vehicle
      (0.9% saline, s.c.) on day 10 after birth. On day 11, mice from each treatment
      group were sacrificed and brains were taken for analysis of neuronal cell
      degeneration, using Fluoro-Jade staining technique. Ketamine, but not diazepam,
      induced a severe degeneration of cells in the parietal cortex. The opposite was
      observed for diazepam in the laterodorsal thalamus. The most pronounced cell
      degeneration was seen in parietal cortex of mice exposed to both ketamine and
      diazepam. At 2 months of age each treatment group was tested for motor activity
      and learning performance. Ketamine and ketamine + diazepam treated mice displayed
      severe deficits of habituation to the test chamber in the spontaneous motor
      activity test, marked deficits of acquisition learning and retention memory in
      the radial arm maze-learning task and less shift learning in the circular swim
      maze-learning task. This study indicates that the observed functional deficits
      can be related to cell degeneration induced during a critical stage of neonatal
      brain development. The potentiated apoptosis induced by ketamine and diazepam may
      have implications for the selection of drugs used in neonatal paediatric
      anaesthesia.

PMID- 15265632
TI  - Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris
      water maze task.
AB  - Homocystinuria is an inherited metabolic disease biochemically characterized by
      tissue accumulation of homocysteine. Affected patients present mental retardation
      and other neurological symptoms whose mechanisms are still obscure. In the
      present study, we investigated the effect of chronic hyperhomocysteinemia on rat
      performance in the Morris water maze task. Chronic treatment was administered
      from the 6th to the 28th day of life by s.c. injection of homocysteine, twice a
      day at 8-h intervals; control rats received the same volume of saline solution.
      Animals were left to recover until the 60th day of life. Morris water maze tasks
      were then performed, in order to verify any effect of early homocysteine
      administration on reference and working memory of rats. Results showed that
      chronic treatment with homocysteine impaired memory of the platform location and
      that homocysteine treated animals presented fewer crossings to the place where
      the platform was located in training trials when compared to saline-treated
      animals (controls). In the working memory task, homocysteine treated animals also
      needed more time to find the platform. Our findings suggest that chronic
      experimental hyperhomocysteinemia causes cognitive dysfunction and that might be
      related to the neurological complications characteristic of homocystinuric
      patients.

PMID- 15265633
TI  - Basolateral amygdala dopamine receptor antagonism modulates initial reactivity to
      but not habituation of the acoustic startle response.
AB  - Although the basolateral amygdala (BLA) plays a role in the habituation to
      sensory stimuli, the receptor mechanisms mediating this process remain unclear.
      In the present study, we investigated the role of BLA dopamine (DA) in the
      habituation of the acoustic startle response (ASR) with intra-BLA infusions of DA
      receptor antagonists. Male Long Evans rats were subjected to startle pulses over
      two consecutive once-daily sessions. Prior to testing on Day 1, separate groups
      of animals received bilateral intra-BLA infusions of a D1 (SCH 23390: 0, 3.2, 6.4
      microg per side) or a D2/D3 (raclopride: 0, 2.5, 5.0 microg per side) receptor
      antagonist. Animals were retested 24h later (Day 2) without prior drug infusion
      in order to assess possible treatment effects on within- and between-session
      habituation of the ASR. As expected, within- and between-session habituation was
      observed in vehicle-treated controls. Within-session habituation was also seen in
      SCH 23390- and raclopride-treated animals both on Day 1 as well as 24h later (Day
      2). Evidence of between-session habituation was observed in SCH 23390-treated
      animals. However, compared to vehicle, intra-BLA SCH 23390 or raclopride
      attenuated the initial startle response on Day 1, but not Day 2. No evidence of
      between-session habituation was found in raclopride-treated animals, although
      this probably reflected the attenuated initial response to the startling stimulus
      on Day 1 rather than a reduced rate of habituation on Day 2. The present study
      suggests that while BLA DA is not involved in habituation of the ASR, it may
      mediate the perceived aversive nature of the initially startling stimuli.

PMID- 15265634
TI  - Comparison of the role of somatosensory stimuli in maze learning in a blind
      subterranean rodent and a sighted surface-dwelling rodent.
AB  - We compared the role of tactile perception in maze learning in the blind mole rat
      and in the laboratory rat. Both species were tested in each of two mazes that
      were identical in complexity but differed in tunnel width and height: the first
      was only slightly wider than the animal's body width (narrow maze) while the
      second was about twice the animal's body width (wide maze). We found that the
      performances of rats tested in the narrow maze were significantly lower than
      those tested in the wide maze, as measured by time and number of errors to reach
      the end of the maze (food reward). The mole rats, in contrast, performed
      significantly better in the narrow maze than in the wide maze. Further, in
      contrast to the rats, the mole rats' locomotion in the wide maze was much less
      continuous than in the narrow maze, reflected in longer and more frequent stops
      at maze junctions, where they pressed the side of their body tightly against the
      tunnel walls. Two main conclusions are derived from this experiment. First,
      subterranean mammals, such as the blind mole rat, appear to rely more on tactile
      stimuli while exploring and learning a complex maze than do sighted surface
      dwelling rodents, such as rat. The extensive use of this somatosensory channel
      may compensate for the mole rats' visual deficiency, and thus substantially
      contribute to their excellent spatial orientation ability, previously
      demonstrated in field and laboratory conditions. Second, poor performance of
      surface-dwelling rodents, such as the rats, in spatial-maze learning tasks might
      not be a consequence of impaired cognitive learning ability, but rather due to
      testing the animal in a physical situation that does not provide the necessary
      somatosensory stimuli found in their natural habitat.

PMID- 15265635
TI  - On the relationship between anticipatory behaviour in a Pavlovian paradigm and
      Pavlovian-to-Instrumental Transfer in rats (Rattus norvegicus).
AB  - The present rat study assessed the relationship between, and the sensitivity of,
      two different tests for appetitive conditioned responding to differences in the
      contingency between a conditioned stimulus (CS) and an unconditioned stimulus
      (US), and to differences in US magnitude. The first test used a Pavlovian-to
      Instrumental Transfer (PIT) paradigm, assessing the capacity of the CS to enhance
      instrumental responding for food. The second test employed a Pavlovian
      conditioning paradigm with an extended CS-US interval, and total number of
      behavioural elements in this interval as a dependent measure. The PIT test proved
      to be sensitive to contingency but not reward magnitude differences, whereas the
      reverse was true for the Pavlovian test. Although there was a significant
      correlation between tests in the magnitude of the CS-induced increase of food
      magazine entries, the main dependent measure from PIT (number of lever presses)
      and that from the Pavlovian test (total number of behavioural elements) did not
      correlate. It is suggested that in the PIT procedure, the CS induces a chain of
      behavioural responses of which lever pressing is just a single element and that
      the Pavlovian test, in principle, is more sensitive.

PMID- 15265636
TI  - Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A
      adrenoceptor subtype.
AB  - The activation of alpha2-adrenoceptors has been reported to impair memory
      functions in both rats and humans. The alpha2-adrenoceptor subtype responsible
      for this detrimental effect is still unknown. The effect of the alpha2-agonists
      clonidine and guanabenz on memory processes, in dependence to the time of
      administration, was evaluated in the mouse passive avoidance test. Clonidine
      (0.02-0.2 mg kg(-1) i.p.) and guanabenz (0.1-0.3 mg kg(-1) i.p.) induced amnesia
      in a dose-dependent manner. From time-course experiments emerged that the
      impairment of memory function was detectable only when clonidine and guanabenz
      were administered 60 min before or immediately after the training test,
      respectively. This detrimental effect was prevented by pretreatment with the
      alpha2-antagonist yohimbine (1-3 mg kg(-1) i.p.) and by the alpha2A-antagonist
      BRL-44408 (0.3-1 mg kg(-1) i.p.). By contrast, the alpha(2B,C) antagonists ARC
      239 (10 mg kg(-1) i.p.) and prazosin (1 mg kg(-1) i.p.) did not revert the
      amnesia induced by both clonidine and guanabenz. At the highest effective doses,
      clonidine and guanabenz were devoid of behavioral side-effects as well as
      maintained unaltered the motor coordination, as revealed by the rota-rod test.
      Furthermore, none of the compounds used modified the spontaneous motility as
      indicated by the Animex apparatus. These results indicate that clonidine and
      guanabenz impaired memory processes in a mouse passive avoidance paradigm through
      the selective activation of the alpha2A-adrenoceptor subtype.

PMID- 15265637
TI  - Anabasine, a selective nicotinic acetylcholine receptor agonist, antagonizes MK
      801-elicited mouse popping behavior, an animal model of schizophrenia.
AB  - The expression of the alpha7-nicotinic acetylcholine receptor is diminished in
      selected brain areas of patients with schizophrenia. This diminished expression
      may account for the pathophysiological deficits of sensory inhibition and smooth
      pursuit eye movement performance in these patients. Furthermore, the deficits in
      sensory inhibition and smooth pursuit eye movement performance in schizophrenia
      appear to be inherited in an autosomal dominant fashion; thus, the "alpha7
      nicotinic acetylcholine receptor-deficiency" may be a necessary condition for
      expression of schizophrenia. This deficit has encouraged speculation about the
      possible therapeutic benefit of selective alpha7-nicotinic acetylcholine receptor
      agonist interventions in this disorder. In view of this, we sought to examine the
      effect of anabasine, a selective alpha7-nicotinic acetylcholine receptor agonist,
      on popping behavior in mice elicited by MK-801. MK-801, a high affinity analogue
      of phencyclidine (PCP), is a noncompetitive N-methyl-D-aspartic acid (NMDA)
      receptor antagonist that binds to the hydrophobic domain of this ligand-gated
      channel. PCP is known to precipitate a schizophreniform psychosis in susceptible
      individuals, causing productive (e.g. hallucinations) deficit (e.g. affective
      blunting, amotivation, and social withdrawal), cognitive and motor symptoms
      similar to those seen in naturally-occurring schizophrenia. Behaviors elicited by
      MK-801 in mice reflect a pharmacologically-induced state of NMDA receptor
      hypofunction (NRH), which has been proposed to exist in schizophrenia. Compounds
      that attenuate MK-801-elicited behaviors, which are identified in this animal
      model, may have the potential to treat schizophrenia, including deficit and
      cognitive symptoms. In the current study, anabasine attenuated MK-801-elicited
      popping at a dose that did not cause clonic seizures. The development of alpha7
      nicotinic acetylcholine receptor agonist interventions for schizophrenia must
      consider their potential liability to elicit seizure activity.

PMID- 15265638
TI  - Cognitive function in young and adult IL (interleukin)-6 deficient mice.
AB  - Interleukin-6 (IL-6) is a cytokine shown to affect brain function and to be
      involved in pathological neurodegenerative disorders such as Alzheimer's disease
      (AD). In the present study we investigated the cognitive function in transgenic
      mice not expressing IL-6 (IL-6 KO) and in wild type (WT) genotype at 4 and 12
      months of age, using a passive avoidance and an eight-arm radial maze tasks.
      Motor function was quantified using an Animex apparatus. Hippocampal choline
      acetyltransferase (ChAT) activity was evaluated in both genotypes. No difference
      was observed in both genotypes for spontaneous motor activity. The mean latency
      (s) to re-enter the shock box, was similar in both young mutant and WT mice.
      However, a decreased sensitivity (50%) to scopolamine (1 mg/kg) in mutant
      compared to WT mice, was obtained. IL-6 KO mice exhibited a facilitation of
      radial maze learning over 30 days, in terms of a lower number of working memory
      errors and a higher percentage of animals reaching the criterion as compared with
      WT genotype tested at both ages. Furthermore, mutant mice, at the age of 12
      months, showed a faster acquisition (22 days versus 30 days to reach the
      criterion). The pattern of arm entry exhibited by IL-6 KO mice showed a robust
      tendency to enter an adjacent arm at both ages, while WT only at the age of 4
      months. ChAT activity was inversely correlated with memory performance. These
      findings suggest a possible involvement of IL-6 on memory processes, even if the
      mechanism remains still unclear.

PMID- 15265639
TI  - Effects of changing reward on performance of the delayed spatial win-shift radial
      maze task in pedunculopontine tegmental nucleus lesioned rats.
AB  - Because it was designed to assess working memory, the delayed spatial win-shift
      (DSWS) radial maze task has been used to investigate the involvement of
      corticostriatal structures in executive processing. Excitotoxic lesions of the
      pedunculopontine tegmental nucleus (PPTg) produce profound deficits in
      performance of this task that are not accounted for by motor impairment. Thus,
      PPTg DSWS deficits are hypothesized to support a role for PPTg in complex
      cognitive processing. However, other studies indicate that the behaviour of PPTg
      lesioned rats varies depending on level of motivational excitement, assessed by
      the presence or absence of deprivation, or by manipulations of reward value.
      Since DSWS performance may also be affected by motivational dysfunction, the
      present experiment was conducted to examine the effects of post-surgical
      presentation of a more positive food reward (chocolate drops) on the DSWS
      retention performance of PPTg lesioned rats. Results confirmed a PPTg lesion
      deficit: lesioned rats made significantly more errors in both training and test
      phases, and made errors significantly earlier in their choice sequence in the
      test phase. Main effects of phase on number of errors indicated that the PPTg
      test phase deficit was not simply the result of a carry-over impairment from the
      training phase. PPTg rats receiving chocolate made significantly fewer errors
      than PPTg rats receiving food pellets. Results suggest that PPTg DSWS deficits
      are not the result of altered motivation or hedonic appreciation of reward value
      (or reward change) and therefore support the hypothesis of executive cognitive
      deficits in PPTg lesioned rats.

PMID- 15265640
TI  - L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats.
AB  - Peripherally and locally administered rotenone (an inhibitor of mitochondrial
      complex I) has been proposed as a model of Parkinson's disease (PD) as it induces
      nigrostriatal degeneration associated with alpha-synuclein inclusions. If
      rotenone-induced symptoms represent a model of PD, than they should be
      counteracted by L-DOPA. To answer this question, rats were treated with rotenone
      2.5 mg/kg over 48 days. Behavioural data showed a strong increase in catalepsy, a
      decrease in locomotor activity and biochemical data showed a significant
      depletion of dopamine levels in the striatum (Cpu) and substantia nigra in
      rotenone treated animals compared to vehicle. To examine the effectiveness of L
      DOPA in reversing the motor deficit in rats, a dose of L-DOPA (10 mg/kg) in
      combination with the peripheral amino acid decarboxylase inhibitor benserazide
      were daily administrated intraperitonially for a period of 10 days in the
      rotenone-treated rats. This treatment counteracted catalepsy and increased
      locomotor activity and number of rearings but decreased inactive sitting. In this
      animal model (rotenone model), catalepsy tests and motor activities showed that
      the clinically used anti-parkinsonian drug L-DOPA substitutes rotenone-induced
      dopamine (DA) deficiency.

PMID- 15265641
TI  - Monocular sleep in male domestic chicks.
AB  - Behavioural sleep during the first 2 weeks after hatching was studied in male
      chicks reared with an imprinting object (I-chicks) and in social isolation (NI
      chicks). Time spent in sleeping with both eyes closed (binocular sleep) decreased
      gradually with age in both I-chicks and in NI-chicks whilst the number of
      episodes of binocular sleep decreased with age in NI-chicks but not in I-chicks.
      The pattern of monocular sleep (only one eye closed) of both I-chicks and NI
      chicks showed no significant bias towards predominant left- or right-eye closure
      during the first week. During the second week, I-chicks showed a tendency towards
      more pronounced left-eye closure with a peak on day 10, whilst NI-chicks showed a
      tendency for more pronounced right-eye closure with peaks on days 9 and 11. In a
      different group of chicks, changing the colour of the imprinting object on day 8
      produced a shift towards right-eye closure. In contrast, the removal of the
      imprinting object on day 8 did not cause any change in the pattern of monocular
      sleep. Differences with respect to sleeping patterns previously observed in
      females chicks are discussed.

PMID- 15265642
TI  - Differences in spatial learning comparing transgenic p75 knockout, New Zealand
      Black, C57BL/6, and Swiss Webster mice.
AB  - Four strains of mice were compared regarding their relative abilities to solve
      the Morris water maze test of spatial memory. Members of the New Zealand Black
      (NZB) strain revealed steady improvement over the 6 days of training comparable
      to C57BL/6 mice. The neurotrophin low affinity receptor p75 knockout mouse, in
      which the binding region is rendered refractory to ligand, displayed profound
      deficits in the acquisition of this task. Members of the Swiss Webster strain
      performed intermediate between the poor performance of the p75 mice and the
      progressively improving learning curves of the NZB and C57 mice. The present
      results support the notion that interference with functioning of nerve growth
      factor (NGF) receptors on forebrain cholingergic neurons negatively impacts the
      animal's ability to utilize the spatial cues necessary for successful spatial
      navigation. This effect on NGF receptors was more behaviorally disrupting than
      the influence of neocortical and hippocampal ectopias as present in the NZB mice.
      These results support the use of the p75 knockout mouse as a model of forebrain
      cholinergic neuron dysfunction. On the other hand, these results do not support
      the use of the NZB mouse as an animal model of human learning disability and
      dementia.

PMID- 15265643
TI  - Fetal habituation correlates with functional brain development.
AB  - In this study, we divided 26 fetuses at 32-37 weeks of gestation into three
      groups using combined criteria of gestational age and behavioral indicators. We
      investigated fetal habituation to vibroacoustic stimulation (VAS). Fetuses showed
      habituation from at least 32 weeks of gestation. Furthermore, fetuses less
      developed from behavioral standpoint took significantly more trials to achieve
      habituation than developed fetuses even in the same gestational age. Taken
      together with these data, it was proved that there was a relationship between
      aspects of behavioral development and habituation.

PMID- 15265644
TI  - Neurotoxic lesion of anteromedial/posterior parietal cortex disrupts spatial maze
      memory in blind rats.
AB  - The primary visual cortex of rats is surrounded laterally (in Oc2L) and medially
      (in Oc2M) by several peristriate visual areas. Previous studies from our
      laboratory demonstrated that bilateral lesions in Oc2L result in visual pattern
      discrimination deficit, and in failure to solve a conditional discrimination
      which requires figure-background association. In contrast, neurotoxic lesions of
      the rostral part of Oc2M (which contains the anteromedial and anterior
      peristriate visual areas, collectively referred to as AM complex) result in
      deficits in visuospatial discrimination, and in disruptions in visual tasks
      involving spatial memory. The objective of this study was to behaviorally test
      the role of AM complex in a spatial memory task in absence of visual cues. For
      this purpose, we analyzed memory retention of Lashley III maze in blind rats
      after bilateral ibotenate lesions in AM complex, or in the primary visual cortex
      (V1, Oc1), to test the hypothesis that AM complex is essential for this cognitive
      task. The results showed a significant loss of memory retention of the maze in
      rats with lesions in AM complex, but not in rats with lesions in V1. Furthermore,
      the retention loss in rats with AM complex lesions was positively and
      significantly correlated with the size of the lesion. The results indicate a
      critical role of AM complex in spatial memory mechanisms independent on visual
      cues. A probable homology of rat AM complex with the posterior parietal cortex of
      primates is discussed.

PMID- 15265645
TI  - Aged neuropeptide Y transgenic rats are resistant to acute stress but maintain
      spatial and non-spatial learning.
AB  - The behavioral phenotype of five-month-old rats overexpressing neuropeptide Y
      (NPY) has previously been described [Proc Natl Acad Sci USA 97 (2000) 12852]. In
      this transgenic rat model, there is central overexpression of prepro-NPY mRNA and
      NPY peptide in the hippocampus and hypothalamus and decreased Y1 binding sites
      within the hippocampus. These molecular and neurochemical events led to altered
      anxiety profile and learning abilities in NPY-overexpressing rats. In the present
      study, anxiety and learning/memory related behaviors were examined in one-year
      old NPY-transgenic rats in order to assess any behavioral changes that may have
      occurred during the aging process. As observed in 5-month-old overexpressing
      rats, aged NPY-transgenic animals are resistant to acute physical restraint
      stress measured by the elevated-plus maze and demonstrate anxiolytic-like
      activity in the open field. However, in contrast to data in young rats, there was
      no significant difference between aged wildtype and NPY-transgenic animals in
      relation to spatial and non-spatial memory as indicated by the (allo- and ego
      centric) Morris water maze and object recognition test. It would thus appear that
      the anxiolytic-like profile observed in young NPY-overexpressing rats is
      maintained in older animals providing further evidence for a role for NPY in
      anxious behaviors. However, the cognitive deficits observed in young rats do not
      appear to occur in older animals suggesting the existence of compensatory
      mechanisms leading to a reversal of the learning deficits noted in younger
      animals. These results also provide additional evidence for the mechanistic
      dissociation between anxiety and cognition-related behaviors modulated by NPY.

PMID- 15265646
TI  - An investigation of the effect of tacrine and physostigmine on spatial working
      memory deficits in the olfactory bulbectomised rat.
AB  - The olfactory bulbectomised (OB) rat is being increasingly used as a model of
      impaired learning and mnemonic functioning. In this study the model has been
      utilised to determine the effect of the acetylcholinesterase inhibiting compounds
      tacrine and physostigmine on spatial working memory deficits associated with the
      OB rat. One-hundred and twenty male rats were randomly allocated to OB or sham
      operated groups and received chronic i.p. treatment with either saline,
      physostigmine (0.1 mg/kg) or tacrine (0.1 and 0.3 mg/kg). Two weeks after
      beginning treatment animals were tested on the Morris water maze and open field
      test. The results indicated that the OB surgery was associated with spatial
      working memory disturbances that were effectively attenuated with both doses of
      tacrine, but not physostigmine. Increased hyperactivity and defecation was
      observed in OB animals in the Open-field test, however, these changes were not
      ameliorated by either drug treatment. The ability for tacrine but not
      physostigmine to attenuate OB cognitive deficits may be associated with the
      different half-life of these compounds. This study provides further support for
      the use of the OB rat as a drug discovery model for the investigation of novel
      therapeutic compounds that target the cholinergic system.

PMID- 15265647
TI  - Effect of dorsal periaqueductal gray lesions on cardiovascular and behavioral
      responses to cat odor exposure in rats.
AB  - Previously we demonstrated Fos expression in the dorsal periaqueductal gray
      (DPAG) of the rat following cat odor exposure. Further work correlated the
      response to cat odor with a sustained blood pressure increase and deployment of
      defense behavior. It was therefore of interest to determine whether lesions of
      the DPAG would abolish these two effects of cat odor exposure. Male Wistar rats
      were given excitotoxic NMDA (N-methyl-D-aspartate) lesions of the DPAG and
      anterior tectum under halothane, then implanted with blood pressure telemetric
      probes. Sham lesions were made with saline. Rats were then exposed to cat odor
      with a hide option, followed 2 weeks later by re-exposure to cat odor without a
      hide option. Controls were exposed to rat odor in the same way. Trends toward
      attenuation in defense and cardiovascular indices were found in lesioned rats for
      cat odor exposure with a hide option, but these were not significant. Re-exposure
      to cat fur without a hide option enhanced the cardiovascular response and under
      these conditions, lesioned rats showed a significant change of the heart rate and
      locomotor activity response to cat fur. However, the blood pressure response was
      not significantly attenuated. Thus, the present results support the Fos data and
      indicate that the DPAG is involved in the expression of some but not all of the
      cardiovascular and behavioral components of the response to cat odor.

PMID- 15265648
TI  - Maintenance in working memory or response selection? Functions of NMDA receptors
      in the pigeon "prefrontal cortex".
AB  - The prefrontal cortex is involved in various aspects of working memory like
      stimulus maintenance and response selection functions. Neurobehavioral studies
      and neurocomputational models assume a role for NMDA receptors in prefrontal
      cortex for maintenance processes, while our previous studies on NMDA receptors in
      the avian prefrontal cortex-analogue, the nidopallium caudolaterale (NCL), showed
      them to be involved in response selection functions. Various tasks used in PFC
      related research address in fact both functions, so they cannot disambiguate
      their separate contributions to performance. In order to investigate the role of
      NMDA receptors in avian NCL for stimulus maintenance and response selection, we
      trained pigeons in a delayed matching-to sample (DMTS) task, requiring both
      functions, and a simultaneous matching to sample (SMTS) task, requiring only
      response selection. After reaching criterion, pigeons had to perform the tasks
      alternately under local NMDA receptor blockade in NCL (DL-AP5) and after infusion
      of vehicle (saline solution). Blockade of NCL-based NMDA receptors led to
      significant increases in error rates in both DMTS and SMTS--compared with the
      same subjects' performance during training and in the control condition. However,
      there was no additional increase in errors due to the additional maintenance
      component, so the impairment appears to be due to deficits in adequate selection
      of responses, the function necessary for both tasks. We conclude that NMDA
      receptors in the pigeon NCL participate in response selection rather than
      stimulus maintenance in tasks requiring the processing of context information.

PMID- 15265650
TI  - Paw preference in dogs: relations between lateralised behaviour and immunity.
AB  - Paw use in a task consisting of the removal of a piece of adhesive paper from the
      snout was investigated in 80 mongrel and pure-bred domestic dogs (Canis
      familiaris). Population lateralisation was observed, but in opposite directions
      in the two sexes (animals were not desexed): males preferentially used their left
      paw, females their right paw. The relationship between immune function and paw
      preference was then investigated. Some immune parameters (total number of white
      blood cells including lymphocytes, granulocytes and monocytes; leukocyte formula;
      total proteins; gamma-globulins) were investigated in a sample of left-pawed (n =
      6), right-pawed (n = 6) and ambidextrous (n = 6) dogs. The results showed that
      the percentage of lymphocytes was higher in left-pawed than in right-pawed and
      ambidextrous dogs, whereas granulocytes percentage was lower in left-pawed than
      in right-pawed and ambidextrous dogs. Moreover, total number of lymphocytes cells
      was higher in left-pawed than in right-pawed and ambidextrous dogs, whereas the
      number of gamma-globulins was lower in left-pawed than in right-pawed and
      ambidextrous dogs. These findings represent the first evidence that brain
      asymmetry modulates immune responses in dogs.

PMID- 15265649
TI  - Deficits in sensorimotor gating and tests of social behavior in a genetic model
      of reduced NMDA receptor function.
AB  - Reduced NMDA receptor function is hypothesized to contribute to the
      pathophysiology of schizophrenia. In order to model chronic and developmental
      NMDA receptor hypofunction, a mouse line was developed that expresses low levels
      of the NMDA R1 subunit (NR1) of the NMDA receptor. The present study tested the
      hypothesis that these NR1 hypomorphic mice would exhibit deficits in sensorimotor
      and conspecific interactions, analogous to deficits observed in schizophrenic
      patients. F1 hybrid mice homozygous for the NR1 hypomorphic mutation (NR1 -/-)
      were generated by crossing heterozygous mice (NR1 +/-) from C57BL/6 and 129 Sv/Ev
      backgrounds. To assess sensorimotor gating, mice were tested in the paradigm of
      prepulse inhibition of acoustic startle. The NR1 hypomorphic mice exhibited
      increased acoustic startle responses and also showed deficits in prepulse
      inhibition. Startle responses were differentially altered by predator odor
      exposure in the male NR1 -/- mice, in comparison to control mice. In a test of
      social affiliation, the wild type mice spent significantly more time
      investigating a novel mouse in comparison to the NR1 -/- mice. In a resident
      intruder test, marked deficits were found in sex-specific aggressive behavior
      between the wild type and mutant mice. These data support the contention that the
      NR1 hypomorphic mice exhibit alterations in sensorimotor gating and typical
      conspecific interactions, reminiscent of behavioral disturbances associated with
      schizophrenia. The NR1 hypomorphic mice could represent a model system to explore
      novel treatment and preventative strategies for certain symptoms of
      schizophrenia.

PMID- 15265651
TI  - Deletion of the 5-HT3 receptor differentially affects behavior of males and
      females in the Porsolt forced swim and defensive withdrawal tests.
AB  - The central serotonin (5-HT) system is important in regulating behaviors
      associated with anxiety and depression. While a fair amount is known about the
      role of 5-HT1 and 5-HT2 receptor subtypes in regulating these behaviors, much
      less is known about the involvement of the 5-HT3 receptor, especially with
      regards to its role in sex differences in behavior. Our goal in the present
      studies was to examine whether deletion of the 5-HT3 receptor produces different
      effects in adult male and female mice on performance in three behavioral tests.
      We examined behavior of male and female mice lacking the 5-HT3 receptor (knock
      out or KO) and their wild-type (WT) littermates in the Porsolt forced swim test
      because of its importance in reliably detecting anti-depressant efficacy. In
      addition, we examined behavior in the defensive withdrawal test and repeated
      exposure to an open field because behavior in these two tests provides measures
      of anxiety. In the Porsolt swim test, sex differences were eliminated by deletion
      of the 5-HT3 receptor while deletion had no effect in the habituation of
      locomotor activity to repeated exposure to an open field. In the defensive
      withdrawal test, deletion of the 5-HT3 receptor had more complex effects though
      these effects tended to be in the opposite direction in males and females.
      Together these results suggest that the 5-HT3 receptor regulates behavior-related
      to depression and anxiety differently in males and females. Whether these effects
      are due to the interaction of 5-HT3 receptor with gonadal hormones requires
      further examination.

PMID- 15265652
TI  - Evidence that the effect of melanocortins on female sexual behavior in preoptic
      area is mediated by the MC3 receptor; Participation of nitric oxide.
AB  - alpha-MSH is involved in reproductive processes and can regulate the expression
      of lordosis, an important component of female reproductive behavior in rats and
      many other species. In this study, we investigated the effects of MSH peptides on
      lordosis behavior when injected in medial preoptic area (POA) of ovariectomised
      rats primed with estradiol. The results show an increase in lordotic activity
      after bilateral administration of alpha-MSH and gamma-MSH. Interestingly, the
      treatment with the MC4 receptor antagonist HS014 did not block the stimulatory
      effect of alpha-MSH. Moreover, the injection of HS014 did not itself modify the
      lordosis quotient. Nitric oxide has been suggested to play a crucial role in the
      regulation of lordosis behavior via stimulation of guanylyl cyclase to synthesize
      cGMP. In order to determine the participation of NO in the effect of the
      melanocortins, another group of rats were treated with L-NAME, an inhibitor of
      NOS, alone or 15 min before the injection of alpha-MSH or gamma-MSH. The
      injection of L-NAME into the POA of E-primed rats 15 min before the test for
      sexual receptivity did not modify significantly the lordosis quotient at the two
      doses examined. The treatment with L-NAME at the lowest dose completely abolished
      the stimulatory effect of alpha-MSH and gamma-MSH on sexual behavior. The results
      indicate that the effects of MSH peptides on female sexual behavior in this area
      are mediated through specific MC receptor, that could be the MC3 receptor and
      that NO mediates the melanocortins effects.

PMID- 15265653
TI  - Participation of the thalamofugal visual pathway in a coarse pattern
      discrimination task in an open arena.
AB  - The purpose of this study was to examine the role of the thalamofugal pathway in
      far-field visual processing. Experiment 1 examined the role of the visual wulst
      and the ectostriatum in a far-field pattern discrimination task in a large open
      arena. Control pigeons, pigeons with ectostriatum lesions, and pigeons with wulst
      lesions were trained to discriminate between four patterns within the arena.
      Ectostriatum-lesioned pigeons were unimpaired and behaved similar to controls. By
      contrast, wulst-lesioned pigeons were severely impaired in the pattern
      discrimination task in the open arena and performed poorer than control pigeons
      and pigeons with ectostriatum lesions. Statistical analyses of regional
      contributions to the observed impairment identified the left visual wulst and
      bilateral hyperstriatum ventrale, which lies outside the wulst, as interesting
      areas. To ensure that the impairment was not due to a general learning deficit,
      experiment 2 involved training the pigeons in a pattern discrimination task
      carried out in an operant chamber, which presumably required use of near-field
      visual information. Wulst-lesioned pigeons were able to learn the task and
      performed at a level no different from control pigeons. The results of these
      experiments support the proposal that the wulst may be important for processing
      far-field information.

PMID- 15265654
TI  - Neuroplasticity after unilateral visual cortex damage in the newborn cat.
AB  - Anatomical, electrophysiological, and behavioral studies implicate extrastriate
      cortex as a major contributor to the sparing of visually guided behaviors
      following lesions of primary visual cortex incurred early in life. Here we report
      considerable sparing of the ability to detect and localize stimuli in the
      hemifield contralateral to unilateral early lesions of all contiguous visually
      responsive primary and extrastriate cortical regions (occipital, visuoparietal,
      and visuotemporal cortices). In the adult cat this same lesion induces a dense
      blindness and cats are unable to orient to any visual stimulus introduced into
      the contralesional hemifield. In the absence of cortical circuits, the neural
      sparing identified following the neonatal lesion is based on the superior
      colliculus and it occurs despite massive retrograde transynaptic degeneration of
      large numbers of retinal ganglion cells.

PMID- 15265655
TI  - Effects of central administration of naloxone during the extinction of appetitive
      sexual responses.
AB  - Several studies indicate that opioids are involved in the control of consummatory
      sexual behavior in male Japanese quail. Naloxone has been reported to increase
      copulatory responses. In the current study, the effect of naloxone on appetitive
      sexual behaviors was assessed during extinction test trials. Naloxone was found
      to substantially reduce appetitive responding, suggesting that opioids
      differentially affect anticipatory and contact components of sexual behavior.

PMID- 15265656
TI  - Somatosensory cell response to an auditory cue in a haptic memory task.
AB  - Neurons in the monkey's anterior parietal cortex (Brodmann's areas 3a, 3b, 1, and
      2) have been reported to retain information from a visual cue that has been
      associated with a tactile stimulus in a haptic memory task. This cross-modal
      transfer indicates that neurons in somatosensory cortex can respond to non
      tactile stimuli if they are associated with tactile information needed for
      performance of the task. We hypothesized that neurons in somatosensory cortex
      would be activated by other non-tactile stimuli signaling the haptic movements-
      of arm and hand--that the task required. We found such cells in anterior parietal
      areas. They reacted with short-latency activity changes to an auditory signal (a
      click) that prompted those movements. Further, some of those cells changed their
      discharge in temporal correlation with the movements themselves, with the touch
      of the test objects, and with the short-term memory of those objects for
      subsequent tactile discrimination. These findings suggest that cells in the
      somatosensory cortex participate in the behavioral integration of auditory
      stimuli with other sensory stimuli and with motor acts that are associated with
      those stimuli.

PMID- 15265658
TI  - Innate immunity in the retina: Toll-like receptor (TLR) signaling in human
      retinal pigment epithelial cells.
AB  - Toll-like receptors (TLRs) are crucial components of innate immunity that
      participate in host defense against microbial pathogens. We evaluated the
      expression and function of TLRs in human retinal pigment epithelial (RPE) cells.
      Real time PCR analysis revealed gene expression for TLRs 1-7, 9, and 10 in RPE
      cells. TLRs 1 and 3 were the most highly expressed TLRs. Protein expression for
      TLRs 2, 3, and 4 was observed on RPE cells and this expression was augmented by
      treatment with poly I:C or interferon-gamma (IFN-gamma). TLR 3 is the receptor
      for dsRNA, an intermediate of virus replication. Because RPE cells express TLR 3
      and are frequently the site of virus replication within the retina, we evaluated
      TLR 3 signaling. RPE cells treated with poly I:C produced IFN-beta but not IFN
      alpha, and this was inhibited by the treatment of RPE cells with anti-TLR 3
      antibody. Human recombinant IFN-beta was shown to be biologically active on RPE
      cells by inhibiting viral replication. Poly I:C treatment of RPE resulted in an
      increase in the production of IL-6, IL-8, MCP-1, and sICAM-1. The presence of
      TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these
      molecules may play an important role in innate and adaptive immune responses
      within the retina.

PMID- 15265659
TI  - ICOS is essential for the development of experimental autoimmune myasthenia
      gravis.
AB  - Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is
      required for effective humoral immunity development. Following immunization with
      Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly
      resistant to clinical experimental autoimmune myasthenia gravis (EAMG)
      development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a
      diminutive germinal center (GC) reaction in secondary lymphoid tissues.
      Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR
      and the AChR dominant alpha146-162 peptide were inhibited by the ICOS gene
      deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction
      of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.

PMID- 15265660
TI  - Differences in the amyloid-beta-induced inflammatory response in microglia from
      C57BL/6 and A/J strains of mice.
AB  - The microglial inflammatory response to Abeta(1-42) stimulation with or without
      IFN-gamma priming was investigated in low and high responder strains of mice, A/J
      and C57BL/6, respectively. A/J microglia showed moderate morphological changes
      upon stimulation with IFN-gamma alone or with Abeta(1-42). Conversely, C57BL/6
      microglia showed major changes in their cellular morphology, which were
      accompanied by a decrease in NO release and a marked increase in TNF-alpha
      production. These results indicate that the magnitude of the microglial
      inflammatory response to Abeta is strongly influenced by genetic factors.
      Individual differences in the regulation of the microglial response may be a key
      player in the rate of development of the neuropathology of AD.

PMID- 15265661
TI  - Involvement of the neuropeptide corticotropin-releasing hormone in an animal
      model of Shigella-related seizures.
AB  - Convulsions are common complications of shigellosis in children. Corticotropin
      releasing hormone (CRH), a stress neurohormone, has been implicated in the
      susceptibility of young children to seizures. We investigated the role of CRH in
      Shigella-related seizures. Pretreatment with Shigella dysenteriae sonicate
      enhanced mice response to pentylenetetrazole (PTZ)-induced seizures. Preinjection
      of antalarmin, a CRH-receptor 1 antagonist, decreased both the mean convulsion
      score (MCS: 1.6 vs. 1.1, p<0.05) and the percent of mice having seizures (48% vs.
      28%, p=0.03). This indicates that CRH plays a role in the increased
      susceptibility to seizures following exposure to S. dysenteriae.

PMID- 15265662
TI  - The induction of splenic suppressor T cells through an immune-privileged site
      requires an intact sympathetic nervous system.
AB  - Antigen injection into the eye's anterior chamber (AC) induces the antigen
      specific suppression of delayed-type hypersensitivity (DTH) that is mediated by
      NKT cells and splenic CD8+ suppressor T cells. Because the AC, uveal tissues, the
      thymus and spleen required to induce anterior chamber-associated immune deviation
      (ACAID) have dense sympathetic innervations, we examined the effects of chemical
      sympathectomy of mice by 6-hydroxydopamine (6-OHDA) on the induction of the
      suppression of contact sensitivity to trinitrophenol (TNP) induced by the
      injection of TNP-bovine serum albumin (BSA) into the anterior chamber. DTH
      measured as contact sensitivity to picrylchloride was not induced in mice that
      received 6-OHDA before immunization with TNP-BSA. Although spleen cells from 6
      OHDA-treated TNP-BSA-immunized mice produced IFN-gamma when stimulated by TNP
      BSA, the number of DTH-initiating hepatic NKT cells was reduced markedly in 6
      OHDA-treated mice. Chemically denervated mice did not produce splenic suppressor
      T cells or thymic NKT cells that activate splenic suppressor T cells. We suggest
      that an intact sympathetic nervous system (SNS) is required to maintain cellular
      immunoregulation.

PMID- 15265664
TI  - Cytokine production, glutamate release and cell death in rat cultured astrocytes
      treated with unconjugated bilirubin and LPS.
AB  - In hyperbilirubinemic newborns, sepsis is considered a risk factor for
      kernicterus. Evidence shows that injury to astrocytes triggers cytokine release.
      We examined the effects of unconjugated bilirubin (UCB) alone, or in combination
      with LPS, on the release of glutamate and cytokines from astrocytes in conditions
      inducing less than 10% of cell death. UCB leads to an increase of extracellular
      glutamate and highly enhances the release of TNF-alpha and IL-1beta, while
      inhibiting the production of IL-6. LPS potentiates immunostimulatory properties
      of UCB. These results point out the role of cytokines and provide a basis for the
      significance of sepsis in UCB encephalopathy.

PMID- 15265663
TI  - CpG oligodeoxynucleotides induce expression of proinflammatory cytokines and
      chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG ODN-mediated
      NF-kappaB activation.
AB  - Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated
      CpG motifs stimulate the cells of the innate immune system through a specific
      receptor called Toll-like receptor-9 (TLR9). It was reported that CpG ODN
      stimulation induces activation of astrocytes and microglia. However, the precise
      intracellular signaling pathways that lead to this glial cell activation have not
      been clearly elucidated. In this study, we found that CpG ODN induce mRNA
      expression of adhesion molecules and matrix metalloproteinase-9 (MMP-9), as well
      as proinflammatory cytokines and chemokines, in mouse astrocytes. CpG ODN
      stimulation in astrocytes induces the activation of IkappaB kinase (IKK) and c
      Jun N-terminal kinase (JNK), whereas it inhibits the constitutive ERK1/2
      activation. The abrogation of JNK activity using a pharmacological inhibitor
      showed that JNK activation is essential for the induction of cytokine and
      chemokine gene expression. This effect of JNK does not require the
      phosphorylation of c-Jun; rather, it works via the potentiation of NF-kappaB
      signaling.

PMID- 15265665
TI  - Microglia phagocytose alloreactive CTL-damaged 9L gliosarcoma cells.
AB  - Intracranial adoptive transfers of alloreactive cytotoxic T lymphocytes (aCTL)
      for brain tumor treatment were safe and showed promise in preclinical and early
      clinical trials. To better understand the endogenous immune responses that may
      ensue following cellular therapy with aCTL, we examined the ability of microglia
      to phagocytose aCTL-damaged and undamaged rat 9L gliosarcoma cells in vitro and
      in vivo. In vitro, 5.5+/-0.9% of microglial cells isolated from adult tumor
      bearing rat brains phagocytosed aCTL-damaged 9L cells, whereas microglia did not
      bind to or ingest undamaged 9L cells. Addition of supernates from either 9L cell
      cultures or from aCTL+9L co-incubate cell cultures to microglia did not
      significantly alter their ability to bind to or phagocytose damaged glioma cells
      even though the latter contained T helper 1 and 2 cytokines. At 3 days following
      intracranial 9L cell infusion, 17.5+/-0.1% of the microglia phagocytosed CFSE
      labeled aCTL-damaged 9L tumor cells within the adult rat brain, confirming the in
      vitro data. The results suggest that microglia within the tumor microenvironment
      of the adult rat glioma model selectively remove damaged, but not undamaged,
      glioma cells.

PMID- 15265666
TI  - Prolactin stimulates maturation and function of rat thymic dendritic cells.
AB  - The current study analyses the effect of PRL, a hormone involved in numerous
      physiological processes, on dendritic cells (DC) of rat thymus. Most thymic DC
      express prolactin receptors (PRL-R) as demonstrated by both immunohistochemistry
      and flow cytometry. PRL administration during 2 or 6 days to fetal thymus organ
      cultures (FTOC) does not increase the proportions of DC in cultures but
      stimulates their differentiation. Furthermore, PRL-treated thymic DC exhibit
      increased allostimulatory capacity in mixed leukocyte reaction (MLR) assays in
      association with increased surface expression of both MHC antigens and the co
      stimulatory molecule CD80. PRL-treated DC also produce increased amounts of pro
      inflammatory cytokines, such as IL-12, TNFalpha and IL-1beta, but not of IL6 or
      IL-10. Our data suggest a key role for IL-12 in the observed changes in the
      allostimulatory capacity of PRL-treated DC. Also, they permit us to hypothesize
      about the physiological role played by PRL in thymus ontogeny.

PMID- 15265667
TI  - The delta-opioid receptor participates in T-cell development by promoting
      negative selection.
AB  - The delta-opioid receptor-1 (DOR-1) as well as delta-opioid enkephalin peptides
      are expressed during maturation of T cells, although the functional significance
      of their expression remains unclear. Based on results which show that the
      administration of the highly selective delta-opioid agonist D-Pen2, D
      Pen5]enkephalin (DPDPE) induces an altered pattern of T-cell differentiation in
      fetal thymic organ culture (FTOC), we hypothesized that DOR-1 is involved in the
      negative selection process. Our results show that superantigen-induced clonal
      deletion is promoted by DPDPE and significantly impaired in DOR-1-deficient mice.
      These results suggest that delta-opioids may play a homeostatic role in the
      negative selection process during T-cell development.

PMID- 15265668
TI  - Modulatory effects on myocardial physiology induced by an anti-Trypanosoma cruzi
      monoclonal antibody involve recognition of major antigenic epitopes from beta1
      adrenergic and M2-muscarinic cholinergic receptors without requiring receptor
      cross-linking.
AB  - It has been proposed that anti-myocardial antibodies (Ab) against
      neurotransmitter (NT) receptors are involved in the immunopathology of chronic
      Chagas' heart disease. We demonstrated that an anti-Trypanosoma cruzi monoclonal
      Ab (mAb), CAK20.12, binds to murine cardiac beta-adrenergic and muscarinic acetyl
      choline (mACh) receptors eliciting abnormal physiological responses on normal
      heart. No cross-linking requirement for mAb actions was demonstrated using Fab
      fragment derived from CAK20.12. mAb binding to synthetic peptides from the second
      extracellular loop of both beta1-adrenergic and mACh receptors, demonstrated by
      ELISA, identified the region of NT receptors involved. Cross-reactivity between
      these peptides and T. cruzi antigen was confirmed by binding inhibition assays.
      These results support the existence of cross-reactivity due to molecular mimicry
      between a parasite antigen and the major antigenic epitopes present on both beta1
      adrenergic and M2-ACh receptors. Its possible relationship with cardiac
      dysfunction during chronic stage of Chagas' disease is also discussed.

PMID- 15265670
TI  - Microglial cell activation in demyelinating canine distemper lesions.
AB  - Microglia cells are the principal immune effector elements of the brain
      responding to any pathological event. To elucidate the possible role of microglia
      in initial non-inflammatory demyelination in canine distemper virus (CDV)
      infection, microglia from experimentally CDV infected dogs were isolated ex vivo
      by density gradient centrifugation and characterized immunophenotypically and
      functionally using flow cytometry. Results from dogs with demyelinating lesions
      were compared to results from recovered dogs and two healthy controls. CDV
      antigen could be detected in microglia of dogs with histopathologically confirmed
      demyelination. Microglia of these dogs showed marked upregulation of the surface
      molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency
      for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86),
      whereas no increased expression was found for CD44 and CD45. Functionally,
      microglia exhibited distinctly enhanced phagocytosis and generation of reactive
      oxygen species (ROS). It was concluded that in CDV infection, there is a clear
      association between microglial activation and demyelination. This strongly
      suggests that microglia contribute to acute myelin destruction in distemper.

PMID- 15265669
TI  - Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting
      experimental autoimmune encephalitis in SJL mice.
AB  - FTY720 is a prodrug for FTY-phosphate, an agonist at four of the five known
      receptors for sphingosine-1-phosphate (S1P). We show that administration of
      either FTY720 or FTY-P to SJL mice with established relapsing-remitting
      experimental autoimmune encephalitis (EAE) results in a rapid and sustained
      improvement in their clinical status, and a reversal of changes in expression of
      mRNAs encoding some myelin proteins and inflammatory mediators. EAE produced by
      adoptively transferring lymph node cells from immunized mice to naive hosts is
      similarly ameliorated by FTY-P. Treatment with FTY-P is accompanied by a dose
      responsive peripheral lymphopoenia.

PMID- 15265671
TI  - 15-deoxy-delta (12,14)-PGJ2 inhibits astrocyte IL-1 signaling: inhibition of NF
      kappaB and MAP kinase pathways and suppression of cytokine and chemokine
      expression.
AB  - We studied the role of 15-deoxy-delta (12,14)-PGJ2 (15d-PGJ2), a macrophage
      inhibitor with reported therapeutic effects on experimental allergic
      encephalomyelitis, in human astrocyte activation in vitro. 15d-PGJ2 inhibited a
      broad range of astrocyte inflammatory gene expression induced by IL-1, including
      cytokines (TNFalpha and IL-6), chemokines (RANTES/CCL5 and IP-10/CXCL10) and
      inducible nitric oxide synthase. 15d-PGJ2 inhibited transactivation of NF-kappaB
      dependent promoters, as well as p38 and JNK MAPK phosphorylation induced by IL-1,
      while having no inhibitory effect on IFN-induced Stat signaling pathways. Our
      results demonstrating 15d-PGJ2-mediated astrocyte deactivation through inhibition
      of NF-kappaB are similar to those described for macrophages, and add astrocytes
      as additional targets for this prostaglandin (PG).

PMID- 15265672
TI  - Increased pro-thyrotropin-releasing hormone transcription in hypophysiotropic
      neurons of Lewis rats.
AB  - The expression of pro-thyrotropin-releasing hormone (pro-TRH) mRNA was analyzed
      in the hypothalamus of inflammatory susceptible LEW/N and resistant F344/N rats
      at baseline and in adrenalectomized and lipopolysaccharide-treated animals. In
      saline-treated control animals, increased pro-TRH transcription was detected in
      LEW/N with respect to F344/N rats. This increased LEW/N pro-TRH expression was
      stable regardless of condition in contrast to F344/N increased pro-TRH
      transcription post-adrenalectomy and decreased pro-TRH after lipopolysaccharide
      administration. The LEW/N increase in pro-TRH mRNA was independent of changes in
      hormonal status suggesting alteration of the thyroid axis at the central level in
      this strain.

PMID- 15265673
TI  - CXCR3 marks CD4+ memory T lymphocytes that are competent to migrate across a
      human brain microvascular endothelial cell layer.
AB  - Chemokines and their receptors may be implicated in leukocyte ingress into brain
      during inflammation observed during the course of multiple sclerosis (MS). To
      address receptor modulation on CD4+ memory T lymphocytes during diapedesis, we
      used an in vitro model of the blood-brain barrier (BBB). We found that only
      memory (CD45RO+) cells transmigrated and type 3 CXC chemokine receptor (CXCR3)
      was enriched on transmigrated cells. CXCR3 depletion of the input population did
      not affect transmigration capability. CXCR3 reemerged on CXCR3 depleted cells
      independently of endothelial cell exposure, but was susceptible to incubation at
      4 degrees C, indicating receptor recycling. We propose that CXCR3 serves as a
      surface marker for cells that have the capacity to cross the BBB, but does not
      play an essential role in extravasation.

PMID- 15265674
TI  - Behavioral testing strategies in a localized animal model of multiple sclerosis.
AB  - To assess neurological impairments quantitatively in an animal model of multiple
      sclerosis (MS), we have used a targeted model of experimental autoimmune
      encephalomyelitis (EAE), which leads to the formation of anatomically defined
      lesions in the spinal cord. Deficits in the hindlimb locomotion are therefore
      well defined and highly reproducible, in contrast to the situation in generalized
      EAE with disseminated lesions. Behavioral tests for hindlimb sensorimotor
      functions, originally established for traumatic spinal cord injury, revealed
      temporary or persistent deficits in open field locomotion, the grid walk, the
      narrow beam and the measurement of the foot exorotation angle. Such refined
      behavioral testing in EAE will be crucial for the analysis of new therapeutic
      approaches for MS that seek to improve or prevent neurological impairment.

PMID- 15265675
TI  - Involvement of substance P, CGRP and histamine in the hyperalgesia and cytokine
      upregulation induced by intraplantar injection of capsaicin in rats.
AB  - Intraplantar (i.pl.) injection of small doses of capsaicin has been shown to
      produce hyperalgesia and upregulation of the levels of proinflammatory cytokines.
      The present work aimed at investigating the possible mediation of these effects
      by sensory neuropeptides and mast cells. Various groups of rats received i.pl.
      injection of capsaicin alone or preceded by the injection of antagonists to
      substance P (SP), calcitonin gene-related protein (CGRP) and histamine (H1, H2)
      or the mast cell blocker ketotifen. All pretreatments prevented, in a dose
      related manner, the capsaicin-induced hyperalgesia. The SP, H2 antagonists and
      ketotifen prevented the upregulation of all cytokines and nerve growth factor
      (NGF) levels, while the CGRP and H1 antagonists showed only attenuation of the
      NGF level.

PMID- 15265676
TI  - Extra-cellular superoxide promotes T cell expansion through inactivation of
      nitric oxide.
AB  - The mechanism and regulation of immunosuppression by nitric oxide (NO) is
      unclear. Extra-cellular superoxide (EC-O2-) production by NADPH-oxidase (phox)
      may prevent NO-mediated suppression of T cell proliferation. p47(phox-/-) mice
      are resistant to experimental allergic encephalomyelitis (EAE), coinciding with
      enhanced splenic NO activity, but no causal link was established. Here, we
      demonstrate such link, since p47(phox-/-) mice developed severe EAE by adoptive
      transfer, but only if NO production during ex vivo donor cell reactivation was
      inhibited. EC-O2- production increased during cognate T cell reactivation, while
      inhibition of EC-O2- by exogenous superoxide dismutase enhanced NO activity. By
      inhibiting NO, EC-O2- production promotes T cell expansion during peripheral
      immune-response activation, not during tissue inflammation.

PMID- 15265677
TI  - Changes of matrix metalloproteinase-9 and its tissue inhibitor (TIMP-1) after
      autologous hematopoietic stem cell transplantation in multiple sclerosis.
AB  - Elevated levels of matrix metalloproteinase-9 (MMP-9) associates with predictors
      of multiple sclerosis (MS) activity. We analysed serum levels and mRNA expression
      of MMP-9 and its inhibitor TIMP-1 in peripheral mononuclear cells of 14 MS
      patients after autologous hematopoietic stem cell transplantation (AHSCT). All
      but 2 patients stabilized after AHSCT. A significant decrease of MMP-9 levels was
      seen up to 36 months after AHSCT. TIMP-1 levels did not change. MMP-9 mRNA levels
      correlated with the CD4+ T cell count (p<0.0001). The significant and persistent
      change in MMP-9 activity after AHSCT may be caused in part by the effect of AHSCT
      in the CD4+ T cell count.

PMID- 15265678
TI  - Generalization of deferred imitation during the first year of life.
AB  - Infants first generalize across contexts and cues at 3 months of age in operant
      tasks but not until 12 months of age in imitation tasks. Three experiments using
      an imitation task examined whether infants younger than 12 months of age might
      generalize imitation if conditions were more like those in operant studies.
      Infants sat on a distinctive mat in a room in their home (the context) while an
      adult modeled actions on a hand puppet (the cue). When they were tested 24 h
      later, 6-month-olds generalized imitation when either the mat or the room (but
      not both) differed, whereas 9-month-olds generalized when both the mat and the
      room differed. In addition, 9-month-olds who imitated immediately also
      generalized to a novel test cue, whereas 6-month-olds did not. These results
      parallel results from operant studies and reveal that the similarity between the
      conditions of encoding and retrieval-not the type of task-determines whether
      infants generalize. The findings offer further evidence that memory development
      during infancy is a continuous function.

PMID- 15265679
TI  - Changes in the structure of children's isometric force variability with practice.
AB  - This study examined the effect of age and practice on the structure of children's
      force variability to test the information processing hypothesis that a reduction
      of sensorimotor system noise accounts in large part for age-related reductions in
      perceptual-motor performance variability. In the study, 6-year-olds, 10-year
      olds, and young adults practiced on 5 consecutive days (15 trials/day),
      maintaining for 15-s trials a constant level of force (5 or 25% of maximum
      voluntary contraction) against an object using a pinch grip (thumb and index
      finger). With increasing age, the amount of force error and variability
      decreased, but the sequential structure of variability increased in irregularity.
      With practice, children reduced the amount of variability by changing the
      structure of the force output so as to be more similar to that of their older
      counterparts. The findings provide further evidence that practice-driven changes
      in the structure of force output, rather than a decline in the amount of white
      noise, largely account for age-related reductions in the amount of force
      variability.

PMID- 15265680
TI  - Functional learning among children, adolescents, and young adults.
AB  - This study examined age-related differences in functional learning performance
      manifested among children, adolescents, and young adults placed in a two-cue
      ecology involving cues with direct relation and inverse relations with the
      criterion. On each trial, participants were instructed to consider the values
      taken by two cues, predict from these two values the value of a criterion, and
      finally examine the corresponding feedback value (i.e., the correct value of the
      criterion for this situation). The authors' hypotheses were that: (a) very few
      children under 11 years of age would be able to learn how to use the inverse
      relation cue for predicting the criterion, although they would be able to
      correctly use the direct relation cue; (b) most adolescents and young adults over
      17 years of age would be able to learn how to use the inverse relation cue and
      combine it with the direct relation cue; and (c) adolescents between 11 and 17
      years of age would show various levels of achievement. In general, these
      predictions were confirmed. Not until 11 years was a substantial proportion of
      participants (23%) able to reject the direct relation hypothesis and select the
      inverse relation hypothesis during learning.

PMID- 15265681
TI  - Working memory and access to numerical information in children with disability in
      mathematics.
AB  - The relationship among working memory, mathematic ability, and the cognitive
      impairment of children with difficulties in mathematics was examined. A group of
      children with difficulties in mathematics (MD) was compared with a group of
      children with a normal level of achievement matched for vocabulary, age, and
      gender (N = 49). The children were required to perform a variety of working
      memory and short-term memory tasks that had been administered 1 year previously.
      Moreover, the children were asked to perform tasks designed to provide
      information about speed of articulation. The results suggest a general working
      memory deficit in children with MD, specifically in the central executive
      component of Baddeley's model and primarily in the ability to inhibit irrelevant
      information. However, the MD children were not impaired in speech rate and
      counting speed tasks, which mainly involve the role of the articulatory loop.

PMID- 15265682
TI  - Tyrosinase-related proteins suppress tyrosinase-mediated cell death of
      melanocytes and melanoma cells.
AB  - The synthesis of melanin intermediates through tyrosinase (TYR) involves the
      production of cytotoxic free radicals. By using recombinant adenoviruses that
      express TYR, tyrosinase-related protein 1 (TYRP1) or DOPAchrome tautomerase
      (DCT), we analyzed the biological function of these proteins with regard to
      melanin production and the growth of melanocytes, fibroblasts, melanoma cells and
      nonmelanoma cancer cells. High-level expression of TYR produced newly synthesized
      melanin and induced cell death in all of these cells. However, when TYRP1 or DCT
      was coexpressed with TYR in melanocytes and melanoma cells, TYR-mediated cell
      death was clearly decreased. This decrease was not observed in nonmelanocytic
      cells. Western blot analysis and measurement of enzyme activity revealed that the
      expression of TYRP1 or DCT had little effect on the amount or activity of
      cointroduced TYR in either the melanocytic or nonmelanocytic cells. In cells
      expressing both TYR and TYRP1 or TYR and DCT, the total amount of melanin and/or
      eumelanin increased substantially more than that in cells expressing TYR alone.
      On the other hand, the level of pheomelanin was similar in these three cell
      types. These findings suggest that TYRP1 and DCT play an important role in
      suppressing TYR-mediated cytotoxicity in melanocytic cells without decreasing TYR
      expression and/or activity. These biological activities of TYRP1 and DCT may work
      through the interaction with TYR in melanosomal compartment.

PMID- 15265683
TI  - Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2
      and Bcl-x(L).
AB  - Lats2, also known as Kpm, is the second mammalian member of the novel Lats tumor
      suppressor gene family. Recent studies have demonstrated that Lats2 negatively
      regulates the cell cycle by controlling G1/S and/or G2/M transition. To further
      understand the role of Lats2 in the control of human cancer development, we have
      expressed the protein in human lung cancer cells by transduction of a replication
      deficient adenovirus expressing human Lats2 (Ad-Lats2). Using a variety of
      techniques, including Annexin V uptake, cleavage of PARP, and DNA laddering, we
      have demonstrated that the ectopic expression of human Lats2 induced apoptosis in
      two lung cancer cell lines, A549 and H1299. Caspases-3, 7, 8, and 9 were
      processed in the Ad-Lats2-transduced cells; however, it was active caspase-9, not
      caspase-8, that initiated the caspase cascade. Inhibitors specific to caspase-3
      and 9 delayed the onset of Lats2-mediated apoptosis. Western blot analysis
      revealed that anti-apoptotic proteins, BCL-2 and BCL-x(L), but not the pro
      apoptotic protein, BAX, were downregulated in Ad-Lats2-transduced human lung
      cancer cells. Overexpression of either Bcl-2 or Bcl-x(L) in these cells lead to
      the suppression of Lats2-mediated caspase cleavage and apoptosis. These results
      show that Lats2 induces apoptosis through downregulating anti-apoptotic proteins,
      BCL-2 and BCL-x(L), in human lung cancer cells.

PMID- 15265684
TI  - Enhancement by other compounds of the anti-cancer activity of vitamin D(3) and
      its analogs.
AB  - Differentiation therapy holds promise as an alternative to cytotoxic drug therapy
      of cancer. Among compounds under scrutiny for this purpose is the physiologically
      active form of vitamin D(3), 1,25-dihydroxyvitamin D(3), and its chemically
      modified derivatives. However, the propensity of vitamin D(3) and its analogs to
      increase the levels of serum calcium has so far precluded their use in cancer
      patients except for limited clinical trials. This article summarizes the range of
      compounds that have been shown to increase the differentiation-inducing and
      antiproliferative activities of vitamin D(3) and its analogs, and discusses the
      possible mechanistic basis for this synergy in several selected combinations. The
      agents discussed include those that have differentiation-inducing activity of
      their own that is increased by combination with vitamin D(3) or analogs, such as
      retinoids or transforming growth factor-beta and plant-derived compounds and
      antioxidants, such as curcumin and carnosic acid. Among other compounds discussed
      here are dexamethasone, nonsteroidal anti-inflammatory drugs, and inhibitors of
      cytochrome P450 enzymes, for example, ketoconazole. Thus, recent data illustrate
      that there are extensive, but largely unexplored, opportunities to develop
      combinatorial, differentiation-based approaches to chemoprevention and
      chemotherapy of human cancer.

PMID- 15265685
TI  - Involvement of iNOS-dependent NO production in the stimulation of osteoclast
      survival by TNF-alpha.
AB  - Osteoclasts, cells primarily responsible for bone resorption, differentiate from
      hematopoietic progenitor cells under the influence of various hormones,
      cytokines, and differentiation factors. Once fully differentiated, osteoclasts
      rapidly die in the absence of any survival factor. We have previously shown that
      tumor necrosis factor alpha (TNF-alpha) promotes the survival of differentiated
      osteoclasts. The expression of inducible nitric oxide synthase (iNOS) and
      consequent NO production is often stimulated under inflammatory conditions. In
      this study, we found that TNF-alpha, but not receptor activator of nuclear factor
      kappa B ligand and interleukin 1, increased the expression of iNOS both at the
      mRNA and protein levels. Subsequently, an enhanced NO level was detected both
      inside the cells and the culture medium of TNF-alpha-stimulated osteoclasts.
      Blocking NOS activity with L-NAME prevented TNF-alpha-induced NO generation by
      osteoclasts and the osteoclast survival stimulated by TNF-alpha. The iNOS
      selective inhibitor L-NIL also suppressed TNF-alpha-induced osteoclast survival,
      whereas low concentrations of NO releaser NOC-18 were sufficient to promote
      osteoclast survival. Furthermore, antiapoptotic and caspase suppressive effects
      of TNF-alpha on osteoclasts were abolished by L-NAME. Our findings indicate that
      iNOS-dependent NO generation contributes to the survival-promoting function of
      TNF-alpha in osteoclasts.

PMID- 15265686
TI  - Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds
      Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney
      epithelial cells.
AB  - The Wnt signaling pathway is central to the development of all animals and to
      cancer progression, yet largely unknown are the pairings of secreted Wnt ligands
      to their respective Frizzled transmembrane receptors or, in many cases, the
      relative contributions of canonical (beta-catenin/LEF/TCF) versus noncanonical
      Wnt signals. Specifically, in the kidney where Wnt-4 is essential for the
      mesenchymal to epithelial transition that generates the tissue's collecting
      tubules, the corresponding Frizzled receptor(s) and downstream signaling
      mechanism(s) are unclear. In this report, we addressed these issues using Madin
      Darby Canine Kidney (MDCK) cells, which are competent to form tubules in vitro.
      Employing established reporter constructs of canonical Wnt/beta-catenin pathway
      activity, we have determined that MDCK cells are highly responsive to Wnt-4, -1,
      and -3A, but not to Wnt-5A and control conditions, precisely reflecting
      functional findings from Wnt-4 null kidney mesenchyme ex vivo rescue studies. We
      have confirmed that Wnt-4's canonical signaling activity in MDCK cells is
      mediated by downstream effectors of the Wnt/beta-catenin pathway using beta
      Engrailed and dnTCF-4 constructs that suppress this pathway. We have further
      found that MDCK cells express the Frizzled-6 receptor and that Wnt-4 forms a
      biochemical complex with the Frizzled-6 CRD. Since Frizzled-6 did not appear to
      transduce Wnt-4's canonical signal, data supported recently by Golan et al.,
      there presumably exists another as yet unknown Frizzled receptor(s) mediating Wnt
      4 activation of beta-catenin/LEF/TCF. Finally, we report that canonical Wnt/beta
      catenin signals cells help maintain cell growth and survival in MDCK cells but do
      not contribute to standard HGF-induced (nonphysiologic) tubule formation. Our
      results in combination with work from Xenopus laevis (not shown) lead us to
      believe that Wnt-4 binds both canonical and noncanonical Frizzled receptors,
      thereby activating Wnt signaling pathways that may each contribute to kidney
      tubulogenesis.

PMID- 15265687
TI  - Interaction between p230 and MACF1 is associated with transport of a glycosyl
      phosphatidyl inositol-anchored protein from the Golgi to the cell periphery.
AB  - The molecular basis by which proteins are transported along cytoskeletal tracts
      from the trans-Golgi network (TGN) to the cell periphery remains poorly
      understood. Previously, using human autoimmune sera, we identified and
      characterized a TGN protein, p230/Golgin-245, an extensively coiled-coil protein
      with flexible amino- and carboxyl-terminal ends, that is anchored to TGN
      membranes and TGN-derived vesicles by its carboxyl-terminal GRIP domain. To
      identify molecules that interact with the flexible amino-terminal end of p230, we
      used this domain as bait to screen a human brain cDNA library in a yeast two
      hybrid assay. We found that this domain interacts with the carboxyl-terminal
      domain of MACF1, a protein that cross-links microtubules to the actin
      cytoskeleton. The interaction was confirmed by co-immunoprecipitation, an in
      vitro binding assay, double immunofluorescence images demonstrating overlapped
      localization in HeLa cells, and co-localization of FLAG-tagged constructs
      containing the interacting domains of these two proteins with their endogenous
      partners. Expression in HeLa cells of FLAG-tagged constructs containing the
      interacting domains of p230 and MACF1 disrupted transport of the glycosyl
      phosphatidyl inositol-anchored marker protein conjugated with yellow fluorescent
      protein (YFP-SP-GPI), while trafficking of the transmembrane marker protein,
      vesicular stomatitis virus glycoprotein conjugated with YFP (VSVG3-GL-YFP), was
      unaffected. Our results suggest that p230, through its interaction with MACF1,
      provides the molecular link for transport of GPI-anchored proteins along the
      microtubule and actin cytoskeleton from the TGN to the cell periphery.

PMID- 15265688
TI  - CLN6, which is associated with a lysosomal storage disease, is an endoplasmic
      reticulum protein.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are severe inherited neurodegenerative
      disorders affecting children. In this disease, lysosomes accumulate
      autofluorescent storage material and there is death of neurons. Five types of NCL
      are caused by mutations in lysosomal proteins (CTSD, CLN1/PPT1, CLN2/TTPI, CLN3
      and CLN5), and one type is caused by mutations in a protein that recycles between
      the ER and ERGIC (CLN8). The CLN6 gene underlying a variant of late infantile NCL
      (vLINCL) was recently identified. It encodes a novel 311 amino acid transmembrane
      protein. Antisera raised against CLN6 peptides detected a protein of 30 kDa by
      Western blotting of human cells, which was missing in cells from some CLN6
      deficient patients. Using immunofluorescence microscopy, CLN6 was shown to reside
      in the endoplasmic reticulum (ER). CLN6 protein tagged with GFP at the C-terminus
      and expressed in HEK293 cells was also found within the ER. Investigation of the
      effect of five CLN6 disease mutations that affect single amino acids showed that
      the mutant proteins were retained in the ER. These data suggest that CLN6 is an
      ER resident protein, the activity of which, despite this location, must
      contribute to lysosomal function.

PMID- 15265689
TI  - Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator
      through its unique N-terminal domain.
AB  - Recently discovered 210-kDa myosin light chain kinase (MLCK-210) is identical to
      108-130 kDa MLCK, the principal regulator of the myosin II molecular motor,
      except for the presence of a unique amino terminal extension. Our in vitro
      experiments and transfected cell studies demonstrate that the N-terminal half of
      MLCK-210 unique tail domain has novel microfilament and microtubule binding
      activity. Consistent with this activity, the MLCK-210 domain codistributes with
      microfilaments and microtubules in cultured cells and with soluble tubulin in
      nocodazole-treated cells. This domain is capable of aggregating tubulin dimers in
      vitro, causing bundling and branching of microtubules induced by taxol. The N
      terminal actin-binding region of MLCK-210 has lower affinity to actin (K(d) = 7.4
      microM) than its central D(F/V)RXXL repeat-based actin-binding site and does not
      protect stress fibers from disassembly triggered by MLCK inhibition in
      transfected cells. Obtained results suggest that while being resident on
      microfilaments, MLCK-210 may interact with other cytoskeletal components through
      its N-terminal domain. Based on available evidence, we propose a model in which
      MLCK-210 could organize cell motility by simultaneous control of cytoskeleton
      architecture and actomyosin activation through the novel protein scaffold
      function of the unique tail domain and the classical MLCK catalytic function of
      the kinase domain.

PMID- 15265690
TI  - HRP-2, a heterogeneous nuclear ribonucleoprotein, is essential for embryogenesis
      and oogenesis in Caenorhabditis elegans.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) have fundamental roles in the
      posttranscriptional control of gene expression. Here, we describe an hnRNP from
      Caenorhabditis elegans(HRP-2), which shares significant homology with mammalian
      hnRNP R, hnRNP Q and ACF, the essential complementation factor in ApoB mRNA
      editing. All four proteins possess a similar molecular architecture, with three
      closely linked RNA-binding domains and a C-terminus that contains RG/RGG repeat
      motifs. An HRP-2::GFP fusion protein was ubiquitously expressed in C. elegans
      during embryogenesis and subsequent larval development. Expression was also
      detected in the hermaphrodite gonad using a specific antibody, suggesting that
      HRP-2 is provided maternally. HRP-2 was predominantly localised to nuclei and
      analysis of transgenic lines expressing C-terminal deletions of HRP-2 defined a
      functional nuclear localisation signal. Analysis by RNAi demonstrated that HRP-2
      was essential for embryogenesis and fertility. Cell divisions were slower in hrp
      2(RNAi) embryos and the majority showed an early embryonic arrest phenotype.
      Shorter exposure to dsRNA allowed development to the twofold stage and the few
      embryos that hatched were abnormal. Adult worms that developed from embryos
      exposed to RNAi were completely sterile due to a failure in oocyte formation.
      These results demonstrate that HRP-2 or its RNA targets are essential for normal
      embryonic development and oogenesis in C. elegans.

PMID- 15265691
TI  - The mouse synemin gene encodes three intermediate filament proteins generated by
      alternative exon usage and different open reading frames.
AB  - We have previously cloned and characterized the human synemin gene, which encodes
      two intermediate filament proteins (IFPs). We now show that the mouse synemin
      gene encodes three different synemin isoforms through an alternative splicing
      mechanism. Two of them, synemin H and M are similar to human alpha and beta
      synemin, and the third isoform, L synemin, constitutes a new form of IFP. It has
      a typical rod domain and a short tail (49 residues) with a novel sequence that is
      produced by a different open reading frame. The synthesis of H/M synemins starts
      in the embryo, whereas the synemin L isoform is present in adult muscles. The H/M
      isoforms are bound to desmin or vimentin in the muscle cells of wild-type mice.
      Using desmin- and vimentin-deficient mice, we have obtained direct evidence that
      synemin is associated with muscle intermediate filaments in vivo. The
      organization of the synemin fibril is disrupted in skeletal and cardiac muscle
      when desmin is absent and in smooth muscle when vimentin is absent. The fact that
      the three synemin isoforms differ in the sequences of their tail domains as well
      as in their developmental patterns suggests that they fulfill different
      functions.

PMID- 15265692
TI  - Telomerase regulation and progressive telomere shortening of rat hepatic stem
      like epithelial cells during in vitro aging.
AB  - Rat hepatic stem-like epithelial cells, LE/2, LE/6, and WB-F344, share some
      phenotypic properties with oval cells, observed in the early stages of
      hepatocarcinogenesis. Here, we describe regulations of telomerase and telomere
      length during in vitro aging of LEs and WB-F344. These cells displayed no
      apparent aging phenotypes for over 140 passages. Telomerase activity and telomere
      length of these cells progressively decreased with the passages, and at the late
      passages, telomere shortening appeared to be reduced as telomerase activity
      increased. Regulation of TERT and TR, key components of telomerase, was similar
      to that of the telomerase activity. LEs possessed weak telomerase activity with a
      slow rate of proliferation compared to WB-F344, and were not tumorigenic, whereas
      WB-F344 was transformed in vitro from intermediate passage. In conclusion, LEs
      and WB-F344 have different biochemical properties, and telomerase activation and
      short telomeres are unlikely necessary for the transformation of WB-F344. TERT
      and TR seem to be the regulators of the telomerase activity. The relationship
      between telomere length and telomerase activity suggests that telomerase
      contributes to the regulation of telomere length in these cells. Our findings
      provide a better understanding of mechanisms in neoplastic transformation of rat
      hepatic stem-like epithelial cells.

PMID- 15265693
TI  - Angiogenic activation of valvular endothelial cells in aortic valve stenosis.
AB  - Here, we demonstrate the angiogenic response of valvular endothelial cells to
      aortic valve (AV) stenosis using a new ex vivo model of aortic leaflets.
      Histological analysis revealed neovascularization within the cusps of stenotic
      but not of non-stenotic aortic valves. Correspondingly, the number of capillary
      like outgrowth in 3D collagen gel was significantly higher in stenotic than in
      non-stenotic valves. Capillary-like sprouting was developed significantly faster
      in stenotic than in non-stenotic valves. New capillary sprouts from stenotic
      aortic valves exhibited the endothelial cell markers CD31, CD34 and von
      Willebrand factor (vWF) as well as carcinoembryonic antigen cell adhesion
      molecule-1 (CEACAM1), Tie-2 and angiogenesis inhibitor endostatin. Western blot
      analyses revealed a significant increase of CEACAM1 and endostatin in stenotic
      aortic valve tissue. Electron microscopic examinations demonstrate that these
      capillary-like tubes are formed by endothelial cells containing Weibel-Palade
      bodies. Remarkably, inter-endothelial junctions are established and basement
      membrane material is partially deposited on the basal side of the endothelial
      tubes. Our data demonstrate the capillary-like sprout formation from aortic
      valves and suggest a role of angiogenesis in the pathogenesis of aortic valve
      stenosis. These data provide new insights into the mechanisms of valvular
      disorders and open new perspectives for prevention and early treatment of
      calcified aortic stenosis.

PMID- 15265694
TI  - Cloning and characterization of cellular senescence-associated genes in human
      fibroblasts by suppression subtractive hybridization.
AB  - Cellular senescence marks the end of the proliferative life span of normal cells
      in tissue culture and occurs after cells have undergone a certain number of
      population doublings (PDLs). It is accompanied by alterations in the pattern of
      gene expression. A specific human embryonic lung diploid fibroblast cell line,
      2BS, has been studied as a model of senescence in our laboratory. Here, we report
      a set of cellular senescence-associated genes identified from suppression
      subtractive cDNA libraries from senescent and young 2BS cells. They include three
      novel genes and six previously identified genes of unknown function. The genes
      whose functions are known belong to various functional pathways that have been
      reported to change with the onset of senescence. These include three pre-mRNA
      splicing factors with reduced expression in senescent cells, indicating that the
      regulation of mRNA splicing is altered during cell senescence. In addition, the
      expression of the gene TOM1 (target of Myb 1), which has not previously been
      associated with cellular senescence, is shown to increase in senescent cells, and
      we demonstrate that the expression of antisense TOM1 gene in 2BS cells can delay
      the progress of senescence.

PMID- 15265695
TI  - TGFbeta down-regulation of the CFTR: a means to limit epithelial chloride
      secretion.
AB  - Transforming growth factor beta (TGFbeta) is a multifunctional cytokine with
      effects on many cell types. We recently showed that in addition to epithelial
      barrier enhancing properties, TGFbeta causes diminished cAMP-driven chloride
      secretion in colonic epithelia, in a manner that is p38 MAPK-dependent. In this
      study, we sought to further delineate the mechanism behind TGFbeta diminution of
      chloride secretion. Using colonic and kidney epithelial cell lines, we found that
      exposure to TGFbeta causes dramatic changes in the expression and localization of
      the apical membrane chloride channel, cystic fibrosis transmembrane conductance
      regulator (CFTR). In TGFbeta-treated colonic epithelia (T84 and HT-29), CFTR mRNA
      was significantly reduced 2-24 h post-cytokine exposure. At a time consistent
      with decreased colonic epithelial secretory responses (16 h), TGFbeta treatment
      caused diminished intracellular CFTR protein expression (confocal microscopy) and
      reduced channel expression in the apical membrane during stimulated chloride
      secretion (biotinylation assay). In comparison, polarized kidney epithelia (MDCK)
      treated with TGFbeta displayed similarly reduced secretory responses to cAMP
      stimulating agents; however, a perinuclear accumulation of CFTR was observed,
      contrasting the diffuse cytoplasmic CFTR expression of control cells. Our data
      indicate that TGFbeta has profound effects on the expression and subcellular
      localization of an important channel involved in cAMP-driven chloride secretion,
      and thus suggest TGFbeta represents a key regulator of fluid movement.

PMID- 15265696
TI  - The mammalian verprolin homologue WIRE participates in receptor-mediated
      endocytosis and regulation of the actin filament system by distinct mechanisms.
AB  - The mammalian verprolin family consists of three family members: WIP, WIRE and
      CR16. WIRE was recently found to bind to WASP and N-WASP and to have roles in
      regulating actin dynamics downstream of the platelet-derived growth factor beta
      receptor. In the current study, the WASP-binding domain of WIRE was identified,
      with the core of the binding motif encompassing amino acid residues 408-412. A
      stretch of aromatic amino acid residues close to the core motif also participates
      in WASP binding. Amino acid substitutions in each of these motifs abrogated WASP
      binding, suggesting that both motifs are involved in the binding of WIRE to WASP.
      Interestingly, WIRE mutants unable to bind WASP were still able to induce a
      reorganisation of the actin filament system, indicating that WASP did not
      participate in the signalling pathway that link WIRE to actin dynamics. In cells
      ectopically expressing WIRE, the endocytosis of the platelet-derived growth
      factor beta-receptor was drastically reduced. However, in contrast to the effect
      on the actin filament system, the WIRE-induced ablation of the receptor
      endocytosis required an intact WASP-binding domain. Moreover, WIRE was more
      efficient than WIP in inhibiting the receptor endocytosis, implicating that these
      two mammalian verprolins have distinct roles in mammalian cells.

PMID- 15265697
TI  - Lco1 is a novel widely expressed lamin-binding protein in the nuclear interior.
AB  - A-type lamins are localized at the nuclear envelope and in the nucleoplasm, and
      are implicated in human diseases called laminopathies. In a yeast two-hybrid
      screen with lamin C, we identified a novel widely expressed 171-kDa protein that
      we named Lamin companion 1 (Lco1). Three independent biochemical assays showed
      direct binding of Lco1 to the C-terminal tail of A-type lamins with an affinity
      of 700 nM. Lco1 also bound the lamin B1 tail with lower affinity (2 microM).
      Ectopic Lco1 was found primarily in the nucleoplasm and colocalized with
      endogenous intranuclear A-type lamins in HeLa cells. Overexpression of prelamin A
      caused redistribution of ectopic Lco1 to the nuclear rim together with ectopic
      lamin A, confirming association of Lco1 with lamin A in vivo. Whereas the major C
      terminal lamin-binding fragment of Lco1 was cytoplasmic, the N-terminal Lco1
      fragment localized in the nucleoplasm upon expression in cells. Furthermore, full
      length Lco1 was nuclear in cells lacking A-type lamins, showing that A-type
      lamins are not required for nuclear targeting of Lco1. We conclude that Lco1 is a
      novel intranuclear lamin-binding protein. We hypothesize that Lco1 is involved in
      organizing the internal lamin network and potentially relevant as a laminopathy
      disease gene or modifier.

PMID- 15265698
TI  - NuMA in rat testis--evidence for roles in proliferative activity and meiotic cell
      division.
AB  - NuMA is a well-characterized organizer of the mitotic spindle, which is believed
      to play a structural role in interphase nucleus. We studied the expression of
      NuMA in rat seminiferous epithelium in detail. Different stages of the cycle of
      the seminiferous epithelium were identified using transillumination.
      Corresponding areas were microdissected and analysed using immunofluorescence,
      immunohistochemistry, or immunoblotting. NuMA was expressed in Sertoli cells,
      proliferating type A and B spermatogonia, and early spermatids but it was absent
      in late spermatids and mature spermatozoa. Interestingly, NuMA-positive primary
      spermatocytes lost their nuclear NuMA at the beginning of long-lasting prophase
      of the first meiotic division. A strong expression was again observed at the end
      of the prophase and finally, a redistribution of NuMA into pole regions of the
      meiotic spindle was observed in first and second meiotic divisions. In
      immunoblotting, a single 250-kDa protein present in all stages of the rat
      seminiferous epithelial cycle was detected. Our results show that NuMA is not
      essential for the organization of nuclear structure in all cell types and suggest
      that its presence is more likely connected to the proliferation phase of the
      cells. They also suggest that NuMA may play an important role in meiotic cell
      division.

PMID- 15265699
TI  - The relationship between Na(+)/H(+) exchanger expression and tyrosinase activity
      in human melanocytes.
AB  - The activity of melanosome-associated tyrosinase in human melanocytes differs
      based on racial skin type. In melanocytes from Black skin, tyrosinase activity is
      high while in White melanocytes the activity of the enzyme is low. Recent studies
      suggest that low tyrosinase activity in White melanocytes may be due to an acidic
      pH environment within the melanosome. Because sodium/hydrogen (Na(+)/H(+))
      exchangers (NHEs) are known to regulate intracellular pH, melanocytes were
      treated with NHE inhibitors to determine what effect this inhibition might have
      on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl
      amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity.
      This inhibition was not due to either direct enzyme inhibition or to a decrease
      in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA,
      cimetidine, or clonidine resulted in little inhibition of tyrosinase activity.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot
      analysis showed that both Black and White melanocytes expressed mRNA and protein
      for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed
      that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase
      Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular
      ATPase (V-ATPase), was found to be present in both White and Black melanosomes,
      indicating that organelles from both racial skin types are capable of being
      acidified. The results suggest that one or more NHEs may help regulate melanosome
      pH and tyrosinase activity in human melanocytes.

PMID- 15265700
TI  - Nuclear shuttling and TRAF2-mediated retention in the cytoplasm regulate the
      subcellular localization of cIAP1 and cIAP2.
AB  - Dynamic subcellular localization is an important regulatory mechanism for many
      proteins. cIAP1 and cIAP2 are two closely related members of inhibitor of
      apoptosis (IAP) family that play a role both as caspase inhibitors and as
      mediators of tumor necrosis factor (TNF) receptor signaling. Here, we report that
      cIAP1 and cIAP2 are nuclear shuttling proteins, whose subcellular localization is
      mediated by the CRM1-dependent nuclear export pathway. Blocking export with
      leptomycin B induces accumulation of both endogenous cIAP1 and epitope-tagged
      cIAP1 and cIAP2 in the nucleus of human cancer cells. We have identified a new
      CRM1-dependent leucine-rich nuclear export signal (NES) in the linker region
      between cIAP1 BIR2 and BIR3 repeats. Mutational inactivation of the NES, which is
      not conserved in cIAP2, reduces cIAP1 nuclear export. Forced relocation of cIAP1
      to the nucleus did not significantly alter its ability to prevent apoptosis.
      Interestingly, co-expression experiments showed that the cIAP1 and cIAP2
      interacting protein TNF receptor-associated factor 2 (TRAF2) plays an important
      role as regulator of IAP nucleocytoplasmic localization, by preventing nuclear
      translocation of cIAP1 and cIAP2. TRAF2-mediated cytoplasmic retention of cIAP1
      was reduced upon TNFalpha treatment. Our results identify molecular mechanisms
      that contribute to regulate the subcellular localization of cIAP1 and cIAP2.
      Translocation between different cell compartments may add a further level of
      control for cIAP1 and cIAP2 activity.

PMID- 15265701
TI  - Contribution of p16(INK4a) to replicative senescence of human fibroblasts.
AB  - In standard conditions of tissue culture, human fibroblasts undergo a limited
      number of population doublings before entering a state of irreversible growth
      arrest termed replicative senescence or M1. The arrest is triggered by a
      combination of telomere dysfunction and the stresses inflicted by culture
      conditions and is implemented, at least in part, by the cyclin-dependent kinase
      inhibitors p21(CIP1) and p16(INK4a). To investigate the role of p16(INK4a), we
      have studied fibroblasts from members of melanoma prone kindreds with mutations
      in one or both copies of the CDKN2A locus. The mutations affect the function of
      p16(INK4a) but not of the alternative product, p14(ARF). The p16(INK4a)-defective
      fibroblasts have an above average life span, compared to the heterozygous and
      normal age-matched controls, but they arrest with characteristics typical of
      senescence. Using agents that are known to bypass M1, such as DNA tumor virus
      oncoproteins or the Bmi1 transcriptional repressor, we provide evidence that
      p16(INK4a) defective cells arrest at a stage that is operationally between M1 and
      M2 (crisis). As well as indicating that p16(INK4a) contributes to but is not
      essential for replicative senescence of human fibroblasts, our data reveal
      considerable heterogeneity in the levels and accumulation of p16(INK4a) in
      different strains.

PMID- 15265702
TI  - Synergistic induction of apoptosis in breast cancer cells by cotreatment with
      butyrate and TNF-alpha, TRAIL, or anti-Fas agonist antibody involves enhancement
      of death receptors' signaling and requires P21(waf1).
AB  - Inhibitors of histone deacetylase (HDAC) are considered as potential anticancer
      agents. We have previously demonstrated that an inhibitor of HDAC, sodium
      butyrate (NaB), induces apoptosis of breast cancer cells in a P53-independent and
      P21(waf1)-dependent manner. In this study, we showed that tumor necrosis factor
      alpha (TNF-alpha), TNF-related apoptosis-inducing ligand (TRAIL), and anti-Fas
      agonist antibody potentiated NaB-induced growth inhibition through synergistic
      induction of apoptosis in breast cancer cell lines (MCF-7, T47-D, and BT-20). In
      MCF-7 cells, NaB increased the expression of death receptors; NaB alone or in
      combination with TNF-alpha, TRAIL, and anti-Fas agonist antibody increased the
      levels of Bid, tBid, and that of cytosolic cytochrome c. Synergistic induction of
      apoptosis was strongly inhibited by dominant-negative Fas-associated death domain
      (FADD) and inhibitors of caspases-8 and -9, indicating that potentiation of
      apoptosis involved key elements of death receptors' signaling pathways. Moreover,
      cotreatment of NaB and ligands of death receptors up-regulated the levels of
      P21(waf1) and that of proliferating cell nuclear antigen (PCNA) associated with
      P21(waf1). Transient transfections of p21(waf1) antisense or p21(waf1) deficient
      for its interaction with PCNA abolished synergistic induction of apoptosis. This
      suggested that potentiation of apoptosis by cotreatments required P21(waf1) and
      its interaction with PCNA. Since breast tumors contain rarely p21 mutations, our
      results may open interesting prospects in the fight against breast cancer.

PMID- 15265703
TI  - Rho-mediated assembly of stress fibers is differentially regulated in corneal
      fibroblasts and myofibroblasts.
AB  - Corneal keratocytes (stromal cells) are activated to fibroblasts and
      myofibroblasts during wound healing. Myofibroblast transdifferentiation is
      accompanied by the expression of alpha-smooth muscle actin (alpha-SMA) and the
      assembly of a robust stress fiber network and larger focal adhesions (FAs). The
      regulation of the assembly of stress fibers was evaluated in cultured corneal
      fibroblast and myofibroblast phenotypes. In both cell types, the inhibition of
      Rho GTPase activity by microinjecting C3 transferase into the cells resulted in
      the disassembly of stress fibers and FAs. However, the inhibition of the Rho
      associated kinases ROKalpha and ROKbeta with their inhibitor, Y27632, or by
      overexpression of their mutant kinase-dead forms resulted in only a partial loss
      of the stress fibers and FAs in myofibroblasts but a total loss in fibroblasts.
      ROK inhibitor-sensitive and -resistant stress fibers in myofibroblasts contained
      alpha-SMA, nonmuscle myosin II, tropomyosin, and calponin. The ROK inhibition
      resistant stress fibers and FAs were lost upon the overexpression of the dominant
      negative form of mDia1 (a mammalian homolog of Drosophila diaphanous protein).
      These findings indicated that while the assembly of stress fibers in fibroblasts
      critically involves both ROK and mDia1, in myofibroblasts, the assembly of alpha
      SMA-containing stress fibers also occurs independently of ROK and involves
      Rho/mDia1.

PMID- 15265704
TI  - Protective role of HSP27 against UVC-induced cell death in human cells.
AB  - It is an intriguing problem whether heat shock proteins (HSPs) play a protective
      role in UVC-induced cell death in human cells, and the problem has not been
      solved. To search for the HSPs involved in UVC resistance, gene expression
      profiles using cDNA array were compared between UVC-sensitive human RSa cells and
      their UVC-resistant variant AP(r)-1 cells. The expression levels of heat shock
      protein 27 (HSP27) were lower in RSa cells than in AP(r)-1 cells. RSa cells
      transfected with sense HSP27 cDNA showed slightly lower sensitivity to UVC
      induced cell death than the control cells transfected with a vector alone and
      much lower sensitivity than RSa cells transfected with the antisense HSP27 cDNA.
      Furthermore, the removal capacities of the two major types of UVC-damaged DNA
      (thymine dimers and (6-4)photoproducts) in the cells with the up-regulation of
      HSP27 were moderately elevated compared with those in the control cells, while
      those in the cells with down-regulation were remarkably suppressed. These results
      suggest that HSP27 is involved in the UVC-resistance of human cells, at least
      those tested, possibly via functioning in nucleotide excision repair.

PMID- 15265705
TI  - Sphingosine kinase activation regulates hepatocyte growth factor induced
      migration of endothelial cells.
AB  - Hepatocyte growth factor (HGF)-induced migration of endothelial cells is critical
      for angiogenesis. Sphingosine kinase (SPK) is a key enzyme catalyzing the
      formation of sphingosine-1-phosphate (S1P), a lipid messenger that is implicated
      in the regulation of a wide variety of important cellular events through both
      intracellular and extracellular mechanisms. The aim of this study was to
      investigate whether activation of SPK is involved in the migration of endothelial
      cells induced by HGF. The biological functions of HGF are mediated through the
      activation of its high-affinity tyrosine kinase receptor, c-met protooncogene. In
      the present study, Treatment of ECV304 endothelial cells with HGF resulted in
      tyrosine phosphorylation of c-Met and activation of SPK in a concentration
      dependent manner. Either Ly294002 or PD98059, specific inhibitor of the PI3K and
      ERK/MAPK pathways, respectively, blocked the HGF-induced activation of SPK. HGF
      stimulation significantly increased intracellular S1P level, but no detectable
      secretion of S1P into the cell culture medium was observed. Treatment of ECV304
      cells with pertussis toxin (PTX) has no effect on the HGF-induced migration,
      indicating extracellular S1P is dispensable for this process. Overexpression of
      wild-type SPK gene in ECV 304 cells increased the intracellular S1P and enhanced
      the HGF-induced migration, whereas inhibition of cellular SPK activity by N,N
      dimethylsphingosine (DMS), a potent inhibitor of SPK, or by expression of a
      dominant-negative SPK (DN-SK) blocked the HGF-induced migration of ECV 304 cells.
      It is suggested that PI3K and ERK/MAPK mediated the activation of SPK and would
      be involved in the HGF-induced migration of endothelial cells. These results
      elucidate a novel mechanism by which intracellularly generated S1P mediates
      signaling from HGF/c-Met to the endothelial cell migration.

PMID- 15265706
TI  - Replication pattern of the pericentromeric region of chromosome 10q and
      expression of the RET protooncogene.
AB  - Regulation of the RET gene is highly specific during embryo development and is
      strictly tissue-specific. Control of transcription depends on mechanisms
      influenced by epigenetic processes, in particular, histone acetylation at regions
      flanking the 5' end of the gene. Since the RET gene is mapped in the
      pericentromeric region of the human chromosome 10, the implication of epigenetic
      processes is even more striking and worth to be investigated in an extended
      chromosomal tract. One experimental approach to study the chromatin status in
      relationship with gene transcription is to assess the replication timing, which
      we did by using fluorescent in situ hybridization in cells expressing or not
      expressing the RET gene. By using probes spanning a 700-kb genomic region from
      the RET locus toward the centromere, we found a relationship between RET
      expression and early replication. Different patterns were observed between cells
      naturally expressing RET and cells induced to expression of RET by treatment with
      sodium butyrate, an inhibitor of histone deacetylases. Three-dimensional analysis
      of the nuclear localization of fluorescent signals by confocal microscopy showed
      difference of localization between the RET probe and a probe for a housekeeping
      gene, G3PDH, located at 12p13.3, in cells that do not express RET, in accordance
      with previous data for other genes and chromosomal regions. However, RET
      expressing cells showed a localization of signals which was not consistent with
      that expected for expressed genes.

PMID- 15265707
TI  - Dynamics of transgene expression in a neural stem cell line transduced with
      lentiviral vectors incorporating the cHS4 insulator.
AB  - Transplantation of genetically manipulated cells to the central nervous system
      holds great promise for the treatment of several severe neurological disorders.
      The success of this strategy relies on sufficient levels of transgene expression
      after transplantation. This has been difficult to achieve, however, due to
      transgene silencing. In this study, we transduced the neural stem cell line RN33B
      with self-inactivating lentiviral vectors and analyzed transgenic expression of
      green fluorescent protein (GFP) in several different settings both in vitro and
      after transplantation to the brain. We found that the transgene was affected of
      silencing both when transduced cells were proliferating and after
      differentiation. To prevent silencing, the cHS4 insulator was incorporated into
      the lentiviral vector. We found that a vector carrying the cHS4 insulator was
      partially protected against differentiation-dependent downregulation in vitro and
      in vivo. However, in proliferating cells, we found evidence for variegation and
      positional effects that were not prevented by the cHS4 insulator, suggesting that
      the mechanism behind silencing in proliferating cells is not the same mechanism
      influencing differentiation-dependent silencing. Taken together, these findings
      favor vector optimization as a strategy for achieving efficient ex vivo gene
      transfer in the central nervous system.

PMID- 15265708
TI  - The coxsackie adenovirus receptor inhibits cancer cell migration.
AB  - The coxsackie and adenovirus receptor (CAR) is a key factor in adenoviral cancer
      gene therapy. Reduced expression of CAR during progression of prostate and
      bladder cancer has been reported. In embryonic development and tissue
      differentiation, CAR is also differentially expressed. This study suggests a role
      of CAR expression in cell adhesion and cell motility of human cancer cells.
      Stable CAR-expressing clones from E-cadherin-deficient A2780 ovarian and CaSki
      cervical cancer cells with originally low and high CAR expression levels,
      respectively, were established. CAR reexpression in otherwise singularly growing
      A2780 parental cells resulted in formation of cell-cell contacts and aggregation
      in cell clusters. CAR overexpression in cell adhesion-forming CaSki cells did not
      result in morphological changes. Migration of the A2780 CAR clones was strongly
      reduced as characterized by using spread-off assays. Using migration chambers,
      formation of satellite colonies was reduced by 97% in CAR-expressing A2780 cell
      clones and by 23% in CAR-expressing CaSki cell clones. Parental A2780 and CaSki
      cells selected for high migratory ability by using migration chambers expressed
      endogenous CAR on lower levels associated with lower adenoviral transduction
      efficiency. Our data suggest CAR as a new inhibitory factor for cancer cell
      migration.

PMID- 15265709
TI  - p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation
      and downregulation of Bcl-x(L).
AB  - The role of p38 mitogen-activated protein kinase (MAPK) in apoptosis is a matter
      of debate. Here, we investigated the involvement of p38 MAPK in endothelial
      apoptosis induced by tumor necrosis factor alpha (TNF). We found that activation
      of p38 MAPK preceded activation of caspase-3, and the early phase of p38 MAPK
      stimulation did not depend on caspase activity, as shown by pretreatment with the
      caspase inhibitors z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and Boc
      Asp(OMe)-fluoromethylketone (BAF). The p38 MAPK inhibitor SB203580 significantly
      attenuated TNF-induced apoptosis in endothelial cells, suggesting that p38 MAPK
      is essential for apoptotic signaling. Furthermore, we observed a time-dependent
      increase in active p38 MAPK in the mitochondrial subfraction of cells exposed to
      TNF. Notably, the level of Bcl-x(L) protein was reduced in cells undergoing TNF
      induced apoptosis, and this reduction was prevented by treatment with SB203580.
      Immunoprecipitation experiments revealed p38 MAPK-dependent serine-threonine
      phosphorylation of Bcl-x(L) in TNF-treated cells. Exposure to lactacystin
      prevented both the downregulation of Bcl-x(L) and activation of caspase-3. Taken
      together, our results suggest that TNF-induced p38 MAPK-mediated phosphorylation
      of Bcl-x(L) in endothelial cells leads to degradation of Bcl-x(L) in proteasomes
      and subsequent induction of apoptosis.

PMID- 15265710
TI  - Altered permeability and modulatory character of connexin channels during mammary
      gland development.
AB  - Abrupt developmental changes occur in structural form and function of connexin
      (Cx) channels in the mouse mammary gland. Microarray study shows that the
      principal connexin isoform in epithelial cells during pregnancy is Cx26, up
      regulated and persisting from the virgin. After parturition, there is rapid
      induction of Cx32. In epithelial plasma membranes, size exclusion chromatography
      reveals that Cx32 organizes initially with Cx26 as heteromeric (Cx26-Cx32)
      hemichannels and later in heteromeric and homomeric Cx32 channels. Dramatic
      alterations of connexin channel function following these developmental changes in
      channel composition are characterized using native channels reconstituted into
      liposomes. Changes to channel stoichiometry increase the allowable physical size
      limits of permeant after parturition; the new Cx32 channels are wider than
      channels containing Cx26. Most remarkably, heteromeric Cx26-Cx32 channels are
      selectively permeability to adenosine 3',5' cyclic phosphate (cAMP), guanosine
      3',5' cyclic phosphate (cGMP), and inositol 1,4,5-triphosphate (IP(3)), whereas
      homomeric channels are not. Homomeric Cx26 and heteromeric channels with high
      Cx26/Cx32 stoichiometry are also inhibited by taurine, an osmolyte playing a key
      role in milk protein synthesis. Taurine effect is reduced where heteromeric
      channels contain Cx32 > Cx26 and eliminated when channels contain only Cx32.
      Connexin channel stoichiometry, permeability, and chemical gating character
      change in precisely the desired fashion after parturition to maximize molecular
      and electrical coupling to support coordinated milk secretion.

PMID- 15265711
TI  - BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear
      retention.
AB  - BRCA1 is involved in maintaining genomic integrity and, as a regulator of the
      G2/M checkpoint, contributes to DNA repair and cell survival. The overexpression
      of BRCA1 elicits diverse cellular responses including apoptosis due to the
      stimulation of specific signaling pathways. BRCA1 is normally regulated by
      protein turnover, but is stabilized by BARD1 which can recruit BRCA1 to the
      nucleus to form a ubiquitin E3 ligase complex involved in DNA repair or cell
      survival. Here, we identify BARD1 as a regulator of BRCA1-dependent apoptosis.
      Using transfected MCF-7 breast cancer cells, we found that BRCA1-induced
      apoptosis was independent of p53 and was stimulated by BRCA1 nuclear export.
      Conversely, BARD1 reduced BRCA1-dependent apoptosis by a mechanism involving
      nuclear sequestration. Regulation of apoptosis by BARD1 was reduced by BRCA1
      cancer mutations that disrupt Ub ligase function. Transfection of BRCA1 N
      terminal peptides that disrupted the cellular BRCA1-BARD1 interaction caused a
      loss of nuclear BRCA1 that correlated with increased apoptosis in single cell
      assays, but did not alter localization or expression of endogenous BARD1.
      Reducing BARD1 levels by siRNA caused a small increase in apoptosis. Our findings
      identify a novel apoptosis inhibitory function of BARD1 and suggest that nuclear
      retention of BRCA1-BARD1 complexes contributes to both DNA repair and cell
      survival.

PMID- 15265712
TI  - Glass-forming property of the system diethyl sulphoxide/water and its
      cryoprotective action on Escherichia coli survival.
AB  - In this work the thermal properties of diethyl sulphoxide (Et2SO), as well as its
      cryoprotective ability are studied and related to other well-known cryoprotectant
      substances, like dimethyl sulphoxide (Me2SO). We have investigated the thermal
      properties of Et2SO/water systems using Differential Scanning Calorimetry at a
      very low heating/cooling rate (2 degrees C/min). Liquid/solid or
      glassy/crystalline transitions have been observed only for the solutions with
      content of Et2SO ranging from 5 up to 40% w/w and/or greater than 85%. In the 45
      75% w/w Et2SO range we have found a noticeable glass-forming tendency and a great
      stability of the amorphous state to the reheating. In samples with Et2SO content
      ranging from 80 to 85%, we observed a great stability of the glass forming by
      cooling, but a lesser stability to the subsequent reheating. The glass-forming
      tendency of these solutions is discussed in terms of existing competitive
      interactions between molecules of Et2SO, on the one hand, and Et2SO and water
      molecules, on the other hand. The results are well explainable on the basis of
      the model structure of water/Et2SO solutions, deduced by Raman and infrared
      studies [J. Mol. Struct. 665 (2003) 285-292]. The cryoprotective ability of Et2SO
      on Escherichia coli survival has been also investigated, and a comparison among
      Et2SO and other widely used cryoprotectants, like Me2SO and glycerol has been
      done. Survival of E. coli, determined after freezing-thawing process, was maximal
      at 45% w/w Et2SO (more than 85% viability). It should be noted that at the same
      concentration the survival is only about 35% in the presence of Me2SO and not
      more than 15% in the presence of glycerol. These features are well consisted with
      the glass-forming properties of Et2SO.

PMID- 15265713
TI  - Pre-treatment inflammation induced by TNF-alpha augments cryosurgical injury on
      human prostate cancer.
AB  - Vascular injury is a major mechanism of cryosurgical destruction. The extent of
      vascular injury may be affected by the addition of molecular adjuvants. This
      study, in addition to determining the injury mechanism in the LNCaP Pro 5 human
      prostate cancer subline grown in a nude mouse, examined the effect of cytokine
      TNF-alpha on cryosurgery of an in vivo microvascular preparation (Dorsal Skin
      Flap Chamber). A comparison of injury data to a thermal model indicated that the
      minimum temperature after moderate cooling, thawing, and hold time required for
      causing necrosis was 3.5+/-6.9 degrees C in TNF-alpha-treated LNCaP Pro 5 tumor
      tissue (n=4) and -9.8+/-5.8 degrees C in TNF-alpha-treated normal skin of the
      nude mouse (n=4). Compared to tissues without TNF-alpha treatment, where the
      minimum temperature required for causing necrosis was -16.5+/-4.3 degrees C in
      LNCaP Pro 5 tumor tissue (n=8) and -24.4+/-7.0 degrees C in normal skin of the
      nude mouse (n=9), the results indicate the local use of TNF-alpha can
      dramatically increase the threshold temperature of cryo-destruction by more than
      10 degrees C (p <0.01). These findings were consistent with the hypothesis that
      vascular-mediated injury is responsible for defining the edge of the cryolesion
      in microvascular-perfused tissue, and therefore pre-induced inflammation can
      augment cryoinjury. The local use of TNF-alpha to pre-inflame prostate cancer
      promises to increase both the ability of freezing to destroy cancer as well as
      improve the ability of ultrasound or other iceball-monitoring techniques to
      predict the outcome of the treatment.

PMID- 15265714
TI  - Hyperactive spruce budworm antifreeze protein expression in transgenic Drosophila
      does not confer cold shock tolerance.
AB  - Drosophila melanogaster, a freeze intolerant and cold shock sensitive insect, was
      transformed with the hyperactive insect antifreeze protein gene (AFP) from the
      spruce budworm, Choristoneura fumiferana. Transformation P-element constructs
      (pCasper) were made with CfAFP 337 isoform DNA using a strong constitutive
      promoter, Actin 5c. This is the first report of insect AFP used to transform
      another insect. Properly folded active insect AFP was only detected when signal
      sequences were used to target proteins to the endoplasmic reticulum for secretion
      into the hemolymph. The 18 residue Drosophila binding protein signal sequence
      (BiP) constructs resulted in transformed fly lines with significantly higher AFP
      expression in hemolymph than when the native C. fumiferana AFP signal sequence
      was used. The resultant transgene fly lines have the highest levels of thermal
      hysteresis, 0.8 degrees C, seen for any engineered Drosophila. Despite the high
      level of expression, even higher than some overwintering fish with natural levels
      of endogenous AFP, the transformants did not display any cold shock resistance
      compared to controls or low AFP expressing lines. These results indicate that
      insect AFP alone cannot protect Drosophila from cold shock and may not be useful
      for Drosophila cryopreservation.

PMID- 15265715
TI  - Cryoinjury in endothelial cell monolayers.
AB  - Developing successful cryopreservation strategies for corneas have proven to be
      more difficult than anticipated, because of the resulting loss of viability and
      detachment of endothelial cells from Descemet's membrane following
      cryopreservation of corneas. The objectives of this study are to develop a more
      detailed understanding of cryoinjury in human corneal endothelial cell (HCEC)
      monolayers and to examine the effects of storage temperature, cryoprotectant type
      and concentration, and cooling/warming rates on HCEC monolayers. Monolayers of
      endothelial cells attached to collagen-coated glass, immersed in an experimental
      solution (with and without cryoprotectant) were cooled at 1 degrees C/min to
      various temperatures (-5 to -40 degrees C), then thawed directly or cooled
      rapidly to -196 or to -80 degrees C before thawing. Cryoprotectants used were
      dimethyl sulfoxide and propylene glycol in concentrations of 1 and 2M. Monolayers
      were assessed for membrane integrity and detachment using SYTO/ethidium bromide
      fluorescent stain. The presence of cryoprotectants resulted in high recovery of
      membrane integrity and low monolayer detachment in monolayers thawed directly
      from temperatures down to -40 degrees C. In contrast, there was excessive
      detachment and loss of membrane integrity in monolayers cooled to -196 degrees C
      compared to monolayers cooled to -80 degrees C. Also, increasing cryoprotectant
      concentrations did not improve recovery of the monolayers. The higher recovery
      and lower detachment after storage at -80 degrees C compared to storage at -196
      degrees C suggest that storage temperatures for corneas should be re-evaluated.

PMID- 15265716
TI  - Addition of anticancer agents enhances freezing-induced prostate cancer cell
      death: implications of mitochondrial involvement.
AB  - Recent evidence suggests that the successful treatment of prostate cancer may
      require adjuvant therapies. Accordingly, a better understanding of the molecular
      mechanisms involved in current treatments may lead to enhanced efficacy by
      providing a basis for adjuvant therapies. In this study, we demonstrate that the
      combination of sub-lethal concentrations of chemotherapeutic agents prior to
      freezing (-15 degrees C) in a prostate cancer cell (PC-3) model results in
      enhanced efficacy over either treatment alone. Morphological analysis revealed
      that necrosis appeared to be the prevalent mode of cell death following adjuvant
      (in vitro) modeling, yet molecular analysis indicated that freezing and
      chemotherapy differentially activated apoptotic cascades through modulating
      opposing members of the Bcl-2 protein family. Freezing results in a time
      dependent increase of the antiapoptotic Bcl-2 protein, while chemotherapy results
      in an increase of the pro-apoptotic Bax protein. Anti-apoptotic Bcl-2 protein
      levels increase over 3-fold following exposure to freezing. 5-Fluorouracil (5-FU)
      causes pro-apoptotic Bax levels to increase 2-fold during the drug exposure. The
      increase in Bax was also apparent following the combination of 5-FU/freezing,
      while Bcl-2 levels were maintained at or below control levels. This led to a
      shift in the Bcl-2 to Bax ratio to a pro-death tendency. Other effective
      cryo/chemo combinations were also found to provide similar effects. The
      combination of cisplatin/freezing resulted in a 4-fold increase in the ratio of
      Bax to Bcl-2 when compared to controls, which represented a 2-fold increase over
      the 5-FU/freezing-combination model. This increase may contribute to the
      continued reduction in cell number observed during the 13-day recovery period.
      Additionally, the addition of an apoptotic caspase inhibitor was not able to
      protect cultures from cell death following combination treatment. In conclusion,
      the data suggest that both Bcl-2 and Bax may, not only, play an important role in
      the efficacy of the cryo/chemo combination, but also the balance between the two
      may determine the role and extent of system destruction.

PMID- 15265717
TI  - Prediction of the glass transition temperature of water solutions: comparison of
      different models.
AB  - The glass transition temperature (Tg) of a sample is an important parameter that
      determines its stability during storage. While Tg can be measured by a variety of
      methods, it is a time-consuming procedure, especially if the sample is to be kept
      at subzero temperatures, in anhydrous conditions, or if sampling a portion of the
      specimen for analysis is cumbersome. Hence, predicting rather than directly
      measuring Tg as a function of the content of the constituents of a blend,
      mixture, or solution can be a powerful tool. Two main models for predicting Tg
      have been proposed: Couchman-Karasz (C-K) and Gordon-Taylor (G-T) formalisms.
      However, many aspects of both are theoretical/terminological in nature, and
      substantial controversy exists about the various experimental approaches to
      measuring Tg as well. Here, we compare C-K and G-T formalisms, as well as related
      problems that arise from the variety of definitions and methods of measuring Tg.
      Water-trehalose solutions are used as an example for application of the analysis.
      However, the same conclusions can be expanded to any other solutions so
      thermodynamical parameters (Tg, DeltaCp, and k) of 20 other commonly used solutes
      are provided. Practical pitfalls related to determining water content, including
      experimental data on thermal gravimetry, are also discussed.

PMID- 15265718
TI  - Functional assessment of human femoral arteries after cryopreservation.
AB  - An established method for the cryopreservation of human femoral arteries for
      subsequent transplantation as allografts has been studied with particular
      attention to preservation of smooth muscle and endothelium. Human femoral
      arteries (HFAs) were harvested from multi-organ donors. Two groups were
      established; a control group of unfrozen HFAs and a group of cryopreserved HFAs.
      Cryopreservation was performed using RPMI solution containing dimethyl sulfoxide
      and the rate of cooling was 1 degrees C/min to -40 degrees C and faster
      thereafter until -150 degrees C was reached. The contraction and relaxation
      responses of unfrozen and frozen/thawed arteries were assessed by measurement of
      the isometric force generated by the HFAs in an organ bath. After thawing
      (warming was at 15 degrees C/min) the maximal contractile response to
      noradrenaline was 43% of the response of unfrozen HFAs. The endothelium
      independent response to sodium nitroprusside was not altered, whereas the
      endothelium-dependent relaxation response to acetylcholine was slightly altered.
      The cryopreservation method used provided limited preservation of the
      contractility of human femoral arteries, and good preservation of both
      endothelium-independent and endothelium-dependent relaxation responses.

PMID- 15265719
TI  - Analysis and detection of binaural interaction in auditory evoked brainstem
      responses by time-scale representations.
AB  - The beta-wave of the binaural interaction component (BIC) in auditory evoked
      brainstem responses has been shown to be an objective measure of binaural
      interaction. However, a reliable and automated detection of this component
      capable of clinical use still remains a challenge. In this study, wavelet based
      time-scale representations of auditory evoked brainstem responses were
      investigated for the analysis of binaural interaction and for an automated
      detection of the beta-wave. Twenty normal hearing subjects with verified normal
      directional hearing and speech intelligibility in noise were included in our
      study. In all of these subjects, the BICs exhibited a characteristic
      concentration of energy in the time-scale domain which allowed for an automated
      detection of the beta-wave. Moreover, our study provides an explanation why the
      beta-wave is hard to detect for larger interaural time delays using time-scale
      entropy based arguments. It is concluded that time-scale representations of
      auditory brainstem responses are well suited for the analysis of binaural
      interaction and allow for an automated detection of the beta-wave.

PMID- 15265720
TI  - Electrocardiogram signals de-noising using lifting-based discrete wavelet
      transform.
AB  - This paper introduces an effective technique for the denoising of
      electrocardiogram (ECG) signals corrupted by nonstationary noises. The technique
      is based on a second generation wavelet transform and level-dependent threshold
      estimator. Here, wavelet coefficients of ECG signals were obtained with lifting
      based wavelet filters. A lifting scheme is used to construct second-generation
      wavelets and is an alternative and faster algorithm for a classical wavelet
      transform. The overall denoising performance of our proposed method is considered
      in relation to several measuring parameters, including types of wavelet filters
      (Haar, Daubechies 4 (DB4), Daubechies 6 (DB6), Filter(9-7), and Cubic B-splines),
      thresholding method, and decomposition depth. Three different kinds of noise were
      considered in this work: muscle artifact noise, electrode motion artifact noise,
      and white noise. Global performance is evaluated by means of the signal-to-noise
      ratio and visual inspection. Numerical results comparing the performance of the
      proposed method with that of nonlinear filtering techniques (median filter) are
      given. The results demonstrate consistently superior denoising performance of the
      proposed method over median filtering.

PMID- 15265721
TI  - Mathematical modeling of temperature mapping over skin surface and its
      implementation in thermal disease diagnostics.
AB  - In non-invasive thermal diagnostics, accurate correlations between the thermal
      image on skin surface and interior human pathophysiology are often desired, which
      require general solutions for the bioheat equation. In this study, the Monte
      Carlo method was implemented to solve the transient three-dimensional bio-heat
      transfer problem with non-linear boundary conditions (simultaneously with
      convection, radiation and evaporation) and space-dependent thermal physiological
      parameters. Detailed computations indicated that the thermal states of biological
      bodies, reflecting physiological conditions, could be correlated to the
      temperature or heat flux mapping recorded at the skin surface. The effect of the
      skin emissivity and humidity, the convective heat transfer coefficient, the
      relative humidity and temperature of the surrounding air, the metabolic rate and
      blood perfusion rate in the tumor, and the tumor size and number on the
      sensitivity of thermography are comprehensively investigated. Moreover, several
      thermal criteria for disease diagnostic were proposed based on statistical
      principles. Implementations of this study for the clinical thermal diagnostics
      are discussed.

PMID- 15265722
TI  - Neural classification of lung sounds using wavelet coefficients.
AB  - Electronic auscultation is an efficient technique to evaluate the condition of
      respiratory system using lung sounds. As lung sound signals are non-stationary,
      the conventional method of frequency analysis is not highly successful in
      diagnostic classification. This paper deals with a novel method of analysis of
      lung sound signals using wavelet transform, and classification using artificial
      neural network (ANN). Lung sound signals were decomposed into the frequency
      subbands using wavelet transform and a set of statistical features was extracted
      from the subbands to represent the distribution of wavelet coefficients. An ANN
      based system, trained using the resilient back propagation algorithm, was
      implemented to classify the lung sounds to one of the six categories: normal,
      wheeze, crackle, squawk, stridor, or rhonchus.

PMID- 15265723
TI  - Quantitative analysis of collagen fiber angle in the submucosa of small
      intestine.
AB  - It is of interest to know how distension changes the angle and content of
      collagen in the submucosa of small intestine. We describe the application of a
      two-dimensional quantitative analysis technology to determine the angles between
      collagen fibers in the submucosa using digital image processing. A polarization
      microscope was used to obtain a series of animal intestinal slice images. The
      images were studied by analyzing the relationship between the pixel values of
      each of the polarized angles to obtain the collagen fiber angle. The statistical
      distribution of the angle as function of the degree of distension can be
      analyzed.

PMID- 15265724
TI  - Fluidics-resolved estimation of protein adsorption kinetics in a biomicrofluidic
      system.
AB  - Protein adsorption on surfaces is a complex phenomenon that is described by the
      balance of convective/diffusive transport of the protein species to the surface
      and its adsorption/desorption at the surface. The extent of binding depends on a
      variety of factors such as protein/surface interactions, availability of binding
      sites, localized concentrations of protein near biomaterial surfaces and flow
      characteristics of the protein in that region. Factors such as time-varying
      flows, complex device geometries, presence of multiple competitive species, or
      possible denaturing of proteins when they attach to the surface make it extremely
      difficult to quantitatively analyze protein interactions with surfaces.
      Adsorption/desorption rate constants are often inferred using simplistic models
      which neglect mass transport and have limited use across different microfluidic
      systems and flow protocols. In this work, we have developed and demonstrated a
      fluidics-resolved model that evaluates protein adsorption, accounting for both
      the fluidic transport and the biochemical kinetics in complex biomicrofluidic
      devices. The model is valid for both flow and static conditions. An automated
      procedure was also developed to extract the "intrinsic" mass-transport
      independent adsorption kinetic rate constants from experimental data using a
      least squares optimization method. The automated data extraction methodology is
      applied to two proteins (alkaline phosphatase and glucose oxidase) that have been
      brought into contact with poly(etheretherketone) and Teflon capillaries. The
      applicability of the procedure in analyzing flow and adsorption in complex
      microfluidic structures is also demonstrated.

PMID- 15265725
TI  - Molecular-beacon-based array for sensitive DNA analysis.
AB  - Molecular beacon (MB) DNA probes provide a new way for sensitive label-free
      DNA/protein detection in homogeneous solution and biosensor development. However,
      a relatively low fluorescence enhancement after the hybridization of the surface
      immobilized MB hinders its effective biotechnological applications. We have
      designed new molecular beacon probes to enable a larger separation between the
      surface and the surface-bound MBs. Using these MB probes, we have developed a DNA
      array on avidin-coated cover slips and have improved analytical sensitivity. A
      home-built wide-field optical setup was used for imaging the array. Our results
      show that linker length, pH, and ionic strength have obvious effects on the
      performance of the surface-bound MBs. The fluorescence enhancement of the new MBs
      after hybridization has been increased from 2 to 5.5. The MB-based DNA array
      could be used for DNA detection with high sensitivity, enabling simultaneous
      multiple-target bioanalysis in a variety of biotechnological applications.

PMID- 15265726
TI  - Determination of prolidase activity using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Proline-containing peptides of the X-proline type are cleaved by the dipeptidase
      prolidase. The classical method of prolidase assay relied on the colorimetric
      estimation of the liberated proline with ninhydrin using acidic media and heat.
      This method, however, gave inconsistent results due to the nonspecificity of the
      ninhydrin color reaction. We report here a method for the detection of the
      liberated proline using matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry. Human sera were incubated with a mixture
      containing the dipeptide glycyl-proline in Tris-HCl supplemented with manganese
      at 37 degrees C for 24h. The samples were precipitated with trifluoroacetic acid
      and centrifuged. An aliquot of the supernatant was mixed with an equal volume of
      ferulic acid solution. An aliquot from this mixture was spotted on a stainless
      steel mass spectrometry grid and analyzed using MALDI-TOF mass spectrometry. The
      activity of the enzyme was determined by the complete disappearance of the glycyl
      proline peak with the concomitant appearance of the proline peak and can be
      expressed in terms of the ratio of the area beneath the proline to the area
      beneath the glycyl-proline peak. Subjects homozygous for prolidase deficiency had
      a ratio ranging from 0.006 to 0.04 while obligatory heterozygotes had a ratio
      ranging from around 1.1 to 2.4. Normal subjects had ratios ranging from 9 to 239.
      Using this method we have unambiguously identified subjects with homozygous or
      heterozygous prolidase deficiency. In addition to the advantage of rapid sample
      preparation time, this method is highly specific, reproducible, and sensitive.

PMID- 15265727
TI  - A telomerase enzymatic assay that does not use polymerase chain reaction,
      radioactivity, or electrophoresis.
AB  - A telomerase assay has been developed for high-throughput screening in 96-well
      microtiter plates. A crude cell lysate which adds telomere repeats to a
      biotinylated DNA primer is the source of telomerase. The telomerase-extended
      primer is hybridized to a digoxigenin-labeled telomere antisense DNA probe. The
      hybrid is further processed by enzyme-linked immunosorbent assay (ELISA) as
      follows. The biotinylated hybrid is captured on streptavidin-coated microtiter
      plates. The immobilized hybrid is probed with alkaline phosphatase
      antidigoxigenin and detected via chemiluminescent readout. The limit of detection
      of a chemically synthesized tetra-telomere repeat was about 10 attomoles.
      Apparent telomerase activity was detected in lysates of 293T cells. The signal to
      background for the assay (ratio of signal for the complete assay mixture divided
      by the signal for the assay mixture without primer) was around 10. An automated
      system that performed unattended runs of up to 17 96-well microtiter plates in 8h
      was constructed.

PMID- 15265728
TI  - Species-differentiable sensing of phosphate-containing anions in neutral aqueous
      solution based on coordinatively unsaturated lanthanide complex probes.
AB  - A new chromogenic/fluorogenic molecular probe was developed for highly selective
      and species-differentiable detection of phosphate-containing anions in neutral
      aqueous solution. The coordinatively unsaturated lanthanide complex, made from
      Eu(III) ion and 2-[(8-hydroxy-5-sulfo-7-quinoline)azo]-1,8-dihydroxy-3,6
      naphthalene disulfonic acid, changed its conformation when binding to the
      incoming target anions, which resulted in differential absorption or fluorescence
      responses. It was demonstrated that not only phosphate and pyrophosphate but also
      DNA and RNA could be clearly distinguished by visible absorption or fluorescence
      spectra. Also, differential responses in absorption spectra were observed when
      AMP, ADP, and ATP were added into the sensing system. Selective quantitation of
      these phosphate-containing anions in aqueous solutions, therefore, can be easily
      available. DNA and RNA were distinguished by different colors and independent
      fluorescence emissions due to their intrinsic differences in beta-D-ribose
      residues. Simultaneous or independent quantitation of DNA and RNA in a mixture
      sample, therefore, is possible without pretreatment with nuclease. Furthermore,
      the influence from the base selectivity can be eliminated by the use of the
      probe. The detection limits of phosphate and 5'-ATP in neutral water were 6.0 x
      10(-7) and 9.0 x 10(-7)M, respectively, by the UV/Vis spectrophotometric method;
      the detection limits were 12.3 ng/mL for DNA by fluorimetry and 2.3mg/L for RNA
      by UV/Vis spectrophotometry.

PMID- 15265729
TI  - Possible sources of dye-related signal correlation bias in two-color DNA
      microarray assays.
AB  - DNA microarray analyses commonly use two spectrally distinct fluorescent labels
      to simultaneously compare different mRNA pools. Signal correlation bias currently
      limits accepted resolution to twofold changes in gene expression. This bias was
      investigated by (i) examining fluorescence and absorption spectra and changes in
      relative fluorescence of DNAs labeled with the Cy3, Cy5, Alexa Fluor 555, and
      Alexa Fluor 647 dyes and by (ii) using homotypic hybridization assays to compare
      the Cy dye pair with the Alexa Fluor dye pair. Cy3 or Cy5 dye-labeled DNA
      exhibited reduced fluorescence and absorption anomalies that were eliminated by
      nuclease treatment, consistent with fluorescence quenching that arises from dye
      dye or dye-DNA-dye interactions. Alexa Fluor 555 and Alexa Fluor 647 dye-labeled
      DNA exhibited little or no such anomalies. In microarray hybridization, the Alexa
      Fluor dye pair provided higher signal correlation coefficients (R2) than did the
      Cy dye pair; at the 95% prediction level, a 1.3-fold change in gene expression
      was significant using the Alexa Fluor dye pair. Lowered signal correlation of the
      Cy dye pair was associated with high variance in Cy5 dye signals. These results
      indicate that fluorescence quenching may be a source of signal bias associated
      with the Cy dye pair.

PMID- 15265730
TI  - Interference in the Coomassie Brilliant Blue and Pyrogallol Red protein dye
      binding assays is increased by the addition of sodium dodecyl sulfate to the dye
      reagents.
AB  - We have investigated the effect of sodium dodecyl sulfate (SDS) upon the response
      of the Coomassie Brilliant Blue (CBB) and Pyrogallol Red-molybdate (PRM) protein
      dye-binding assays to interference from aminoglycosides, ampholytes, detergents,
      phenothiazines, reducing agents, and miscellaneous substances previously reported
      to interfere with the assays. The CBB assay was less prone to interference than
      the PRM assay but gave positive interference with the detergents and the
      phenothiazines and negative interference with dextran sulfate. The PRM assay gave
      positive interference with the aminoglycosides, ampholytes, and phenothiazines
      and negative interference with SDS, citric acid, dextran sulfate, EDTA, oxalic
      acid, and tartaric acid. The level of interference varied in the presence of
      different proteins (albumin, gamma globulin, alpha1-acid glycoprotein, or
      lysozyme) and increased when SDS was added to the dye reagents.

PMID- 15265731
TI  - Release of biotin from biotinylated proteins occurs enzymatically and
      nonenzymatically in human plasma.
AB  - Studies in our laboratory and others indicate that biotin is released from
      biotinylated proteins in vivo and in vitro in human plasma. Using immunoglobulin
      G (IgG) as the model protein and four different biotinylating reagents, we
      investigated the mechanism of release. All of the biotin bonds shared an amide
      link to the carboxyl group of biotin but differed in the chemical links (amide,
      thioether, and hydrazone) between spacer arm and the various functional groups on
      IgG. Biotinylated IgG was incubated with phosphate-buffered saline, plasma, or
      plasma treated to either inactivate enzymes or remove all macromolecules.
      Released biotin was separated from bound biotin by ultrafiltration and
      quantitated by avidin-binding assay. As judged by high-performance liquid
      chromatography, greater than 95% of the released avidin-binding activity was
      biotin. We infer that the amide bond between the biotin and the spacer arm rather
      than the bond attaching the spacer to the protein was cleaved. Sodium dodecyl
      sulfate gel electrophoresis detected no proteolytic degradation of biotinylated
      IgG. Neither heat inactivation of plasma nor ultrafiltration of plasma to remove
      macromolecules completely eliminated biotin cleavage. We conclude that cleavage
      of biotin from protein occurs by both enzymatic and nonenzymatic mechanisms.

PMID- 15265732
TI  - "Cystope tagging" for labeling and detection of recombinant protein expression.
AB  - A labeling and detection method, based on the addition of a single cysteine
      residue at the C terminus of a recombinant protein and the subsequent sulfhydryl
      specific Michael addition to the double bond of maleimide and its derivatives,
      was developed. The method was named "cystope tagging." Sorbit dehydrogenase (SDH)
      from Rhodobacter sphaeroides, a member of the short-chain dehydrogenase family of
      proteins that contains three inherent cysteines, was used as a model recombinant
      protein. By labeling with fluorescein-maleimide, it was demonstrated that only
      the single accessory cysteine is accessible under nonreducing conditions. After
      the addition of beta-mercaptoethanol, the inherent cysteines of SDH were also
      detectable by coupling to fluorescein-maleimide. The data were obtained using
      Autodisplay, an efficient surface expression system in Escherichia coli, but the
      method presented in this article represents a rather general solution for
      analyzing the expression of recombinant proteins, irrespective of the expression
      system used. The authors conclude that cystope tagging is an interesting
      alternative to other tagging methods applied in recombinant protein techniques.

PMID- 15265733
TI  - Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides
      following ceramide glycanase digestion and anthranilic acid labeling.
AB  - Interest in cellular glycosphingolipid (GSL) function has necessitated the
      development of a rapid and sensitive method to both analyze and characterize the
      full complement of structures present in various cells and tissues. An optimized
      method to characterize oligosaccharides released from glycosphingolipids
      following ceramide glycanase digestion has been developed. The procedure uses the
      fluorescent compound anthranilic acid (2-aminobenzoic acid; 2-AA) to label
      oligosaccharides prior to analysis using normal-phase high-performance liquid
      chromatography. The labeling procedure is rapid, selective, and easy to perform
      and is based on the published method of Anumula and Dhume [Glycobiology 8 (1998)
      685], originally used to analyze N-linked oligosaccharides. It is less time
      consuming than a previously published 2-aminobenzamide labeling method [Anal.
      Biochem. 298 (2001) 207] for analyzing GSL-derived oligosaccharides, as the
      fluorescent labeling is performed on the enzyme reaction mixture. The
      purification of 2-AA-labeled products has been improved to ensure recovery of
      oligosaccharides containing one to four monosaccharide units, which was not
      previously possible using the Anumula and Dhume post-derivatization purification
      procedure. This new approach may also be used to analyze both N- and O-linked
      oligosaccharides.

PMID- 15265734
TI  - Design of experiments: an efficient strategy to identify factors influencing
      extraction and derivatization of Arabidopsis thaliana samples in metabolomic
      studies with gas chromatography/mass spectrometry.
AB  - The usual aim in metabolomic studies is to quantify the entire metabolome of each
      of a series of biological samples. To do this for complex biological matrices,
      e.g., plant tissues, efficient and reproducible extraction protocols must be
      developed. However, derivatization protocols must also be developed if GC/MS (one
      of the mostly widely used analytical methods for metabolomics) is involved. The
      aim of this study was to investigate how different chemical and physical factors
      (extraction solvent, derivatization reagents, and temperature) affect the
      extraction and derivatization of the metabolome from leaves of the plant
      Arabidopsis thaliana. Using design of experiment procedures, variation was
      systematically introduced, and the effects of this variation were analyzed using
      regression models. The results show that this approach allows a reliable protocol
      for metabolomic analysis of Arabidopsis to be determined with a relatively
      limited number of experiments. Following two different investigations an
      extraction and derivatization protocol was chosen. Further, the reproducibility
      of the analysis of 66 endogenous compounds was investigated, and it was shown
      that both hydrophilic and lipophilic compounds were detected with high
      reproducibility.

PMID- 15265735
TI  - A capillary electrophoretic assay for ribonuclease H activity.
AB  - A capillary electrophoretic assay was developed to measure the ribonuclease
      (RNase) H activity of human immunodeficiency virus (HIV) type 1 reverse
      transcriptase. Cleavage of a fluorescein-labeled RNA-DNA heteroduplex was
      monitored by capillary electrophoresis. This new assay was used as a secondary
      assay to confirm hits from a high-throughput screening program. Since
      autofluorescent compounds in samples migrated differently from both substrate and
      product in most cases, the assay was extremely robust for assaying enzymatic
      inhibition of such samples, in contrast to a simple well-based approach. The
      assay was broadly applicable to other RNases H, specifically those from human,
      Escherichia coli, and HIV-2, although product profiles varied for each enzyme.

PMID- 15265736
TI  - Protein microarray technology and ultraviolet crosslinking combined with mass
      spectrometry for the analysis of protein-DNA interactions.
AB  - To gain insights into complex biological processes, such as transcription and
      replication, the analysis of protein-DNA interactions and the determination of
      their sequence requirements are of central importance. In this study, we probed
      protein microarray technology and ultraviolet crosslinking combined with mass
      spectrometry (MS) for their practicability to study protein-DNA interactions. We
      chose as a model system the well-characterized interaction of bacterial
      replication initiator DnaA with its cognate binding site, the DnaA box.
      Interactions of DnaA domain 4 with a high-affinity DnaA box (R4) and with a low
      affinity DnaA box (R3) were compared. A mutant DnaA domain 4, A440V, was included
      in the study. DnaA domain 4, wt, spotted onto FAST slides, revealed a strong
      signal only with a Cy5-labeled, double-stranded, 21-mer oligonucleotide
      containing DnaA box R4. No signals were obtained when applying the mutant
      protein. Ultraviolet crosslinking combined with nanoLC/MALDI-TOF MS located the
      site of interaction to a peptide spanning amino acids 433- 442 of Escherichia
      coli DnaA. This fragment contains six residues that were identified as being
      involved in DNA binding by recently published crystal structure and nuclear
      magnetic resonance (NMR) analysis. In the future, the technologies applied in
      this study will become important tools for studying protein-DNA interactions.

PMID- 15265737
TI  - Evaluation of a linear amplification method for small samples used on high
      density oligonucleotide microarray analysis.
AB  - High-density oligonucleotide microarray analysis has proven to be an excellent
      approach for gene expression profiling in human cancers. This technique assesses
      the expression of thousands of genes simultaneously, from at least 5 microg of
      total RNA per sample per experiment. This total RNA requirement poses a challenge
      when studying small, unique clinical samples, like biopsies. Recently, a new
      standardized protocol for small samples was released by Affymetrix, which
      includes a linear amplification step. To evaluate the impact of such
      amplification in the gene expression profiling of human ovarian cancer, we
      compared results obtained from 5 microg and 100 ng of total RNA from the same
      tumor sample, using the standard Affymetrix protocol and the new linear RNA
      amplification protocol, respectively. We identified a small bias in gene
      expression data caused by linear amplification, potentially due to shorter
      elongation products leading to misclassification of probe sets directed to the
      middle-5' region of the transcripts. Interestingly, the magnitude of the bias
      varied when different normalization and expression summary algorithms were used.
      However, this bias does not affect tumor gene expression profiling. Consequently,
      linear amplification may be of utility in cases of extremely low RNA recovery
      from critical and unique samples, such as small biopsies.

PMID- 15265738
TI  - Capillary electrophoretic characterization of PEGylated human parathyroid hormone
      with matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - A capillary electrophoretic method (CE) for characterizing PEGylated human
      parathyroid hormone 1-34 (PTH) with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) is described. CE was used to
      optimize the PEGylation of PTH through control of the reaction pH and the molar
      ratio of reactants with the advantages of minimal sample consumption and high
      separation capacity. The mono-PEGylated PTH (mono-PEG-PTH) was isolated and then
      digested with endoproteinase Lys-C. Resistance to Lys-C digestion on the
      PEGylation sites in the mono-PEG-PTH resulted in patterns of CE electropherograms
      different from that of the native PTH, and the PEGylation sites were assigned
      accordingly. The extent of positional isomers present in the mono-PEG-PTH was
      also determined by quantifying PEGylated fragments in the same CE
      electropherogram. In conclusion, the CE analysis of the Lys-C-digested sample
      allowed for simultaneous analysis of the PEGylation site and the extent of
      positional isomers in the mono-PEG-PTH. The results were confirmed by MALDI-TOF
      MS. This method will be applicable for characterizing PEGylation of other
      therapeutic peptides.

PMID- 15265739
TI  - A method for gene expression analysis by oligonucleotide arrays from minute
      biological materials.
AB  - Gene expression profiling has been widely used in identifying differentially
      expressed genes. One of the most popular formats is oligonucleotide array. A
      limitation of oligonucleotide arrays is the requirement of relatively large
      amounts of biological starting materials for gene expression analysis. We have
      developed a simple method for gene expression profiling from very small amounts
      of biological material by combining exponential (PCR) and linear (T7 RNA
      polymerase) amplification. By modifying the widely used SMART protocol, we
      combined T7 promoter ligation and PCR amplification in one step and generated
      around 0.5 microg of PCRcDNA from 30 ng of total RNA in a single PCR. The PCRcDNA
      was in vitro transcribed by T7 RNA polymerase to generate complementary RNA
      (cRNA), which then was used to hybridize Affymetrix GeneChips. Our results
      demonstrated a linear correlation between the PCR amplification and the
      conventional linear amplification in gene expression ratios of individual
      transcript species between two different RNA preparations. The method was further
      validated by TaqMan reactions. Moreover, both linear and PCR methods showed some
      inherent bias as to which transcripts were detected, suggesting that using both
      in parallel may provide a more comprehensive coverage of the transcriptome
      present in a given sample.

PMID- 15265740
TI  - Development of an enzymatic method for site-specific incorporation of
      desthiobiotin to recombinant proteins in vitro.
AB  - To extend the (strept)avidin-biotin technology for affinity purification of
      proteins, development of reusable biochips and immobilized enzyme bioreactors,
      selective immobilization of a protein of interest from a crude sample to a
      protein array without protein purification and many other possible applications,
      the (strept)avidin-biotin interaction is better when reversible. A gentle
      enzymatic method to introduce a biotin analog, desthiobiotin, in a site-specific
      manner to recombinant proteins carrying a biotinylation tag has been developed.
      The optimal condition for efficient in vitro desthiobiotinylation catalyzed by
      Escherichia coli biotin ligase (BirA) in 1-4h has been established by
      systematically varying the substrate concentrations, reaction time, and pH. Real
      desthiobiotinylation in the absence of any significant biotinylation using this
      enzymatic method was confirmed by mass spectrometric analysis of the
      desthiobiotinylated tag. This approach was applied to affinity purify
      desthiobiotinylated staphylokinase secreted by recombinant Bacillus subtilis to
      high purity and with good recovery using streptavidin-agarose. The matrix can be
      regenerated for reuse. This study represents the first successful application of
      E. coli BirA to incorporate biotin analog to recombinant proteins in a site
      specific manner.

PMID- 15265741
TI  - A time-resolved fluorescence resonance energy transfer-based HTS assay and a
      surface plasmon resonance-based binding assay for heat shock protein 90
      inhibitors.
AB  - Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone required
      for the stability and function of a number of client proteins, many of which are
      involved in cancer development. The natural products geldanamycin (GM) and
      radicicol (RD) are known inhibitors of Hsp90, and their derivatives are being
      developed for the treatment of various cancers. To identify novel Hsp90
      inhibitors, a highly robust time-resolved fluorescence resonance energy transfer
      (TR-FRET)-based HTS assay that measures the binding of biotinylated geldanamycin
      (biotin-GM) to the His-tagged human Hsp90 N-terminal ATP-binding domain (Hsp90N)
      was developed. This assay was optimized in 1536-well plates and was used as the
      primary assay to screen 10(6) compounds. Identified "hits" were then confirmed in
      a scintillation proximity assay (SPA) and a DEAE membrane-based assay for
      [(3)H]AAG binding to Hsp90. In addition, a surface plasmon resonance (SPR) assay
      that measures the direct interaction of Hsp90 with its inhibitors was developed
      and used to further characterize the identified inhibitors. Several potent and
      reversible inhibitors of human Hsp90 with K(d) values measured in the high
      nanomolar range were identified.

PMID- 15265742
TI  - Identification of disulfide bonds and site-specific glycosylation in chicken
      alpha1-acid glycoprotein by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry.
AB  - Recently, we reported the amino acid sequence of chicken alpha1-acid glycoprotein
      (chicken alpha1-AGP) [Biochem. Biophys. Res. Commun. 295 (2002) 587]. In this
      study, we located the disulfide bonds and site-specific glycosylation in chicken
      alpha1-AGP using tryptic digests of carbamidomethylated chicken alpha1-AGP,
      carbamidomethylated completely deglycosylated chicken alpha1-AGP (cd-alpha1-AGP),
      and nonreduced denatured cd-alpha1-AGP by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry. Based on the detection of peptides
      mlz 3037.4 (amino acid sequences 69-76 plus 161-183) and 3453.3 (amino acid
      sequences 69-80 plus 161-183), the two disulfide bonds of chicken alpha1-AGP were
      determined to be located at Cys 6-Cys 146 and Cys 73-Cys 163. The results also
      showed that Asn 16, 70, 77, and 87 were fully glycosylated and that Asn 62 was
      partially glycosylated.

PMID- 15265743
TI  - [3H]Allicin: preparation and applications.
AB  - Allicin (diallylthiosulfinate), the active substance of garlic, has been shown to
      possess a variety of biological activities. Mechanistic and pharmacokinetic
      studies of allicin and its derivatives raise the need for a labeled compound.
      However, labeling of this volatile and unstable liquid requires delicate
      handling. Here, we describe a simple method for the preparation of (3)H-labeled
      allicin. This was achieved by applying synthetic [(3)H]alliin ([2,3
      (3)H]allylcysteine sulfoxide) to a column containing immobilized alliinase [EC
      4.1.1.4.] from garlic. Purification of [(3)H]allicin was done by differential
      adsorbtion of the reaction components on a neutral polystyrene resin, Porapak Q.
      Thiol-containing compounds are known to be the main target of allicin. In this
      work we demonstrated that [(3)H]allicin can be used for the synthesis of labeled
      [(3)H]allylmercapto derivatives of SH peptides and proteins. Thus, we prepared
      [(3)H]S-allylmercaptoglutathione which can be used in metabolic studies.
      Moreover, we showed that incubation of alliinase with [(3)H]allicin led to
      modification of 1.4 cysteine residues per subunit of the enzyme.

PMID- 15265744
TI  - Colorimetric ferrozine-based assay for the quantitation of iron in cultured
      cells.
AB  - The ferrozine-based colorimetric assay described here permits the quantitation of
      iron in cultured cells in amounts ranging between 0.2 and 30 nmol. Ferrous and
      ferric iron were detected equally well by the assay and the accuracy was
      unaffected by other divalent metal cations. This colorimetric assay was used to
      study iron accumulation in brain astrocytes that had been cultured in 24-well
      dishes. Iron complexed to cellular proteins was made accessible to ferrozine by
      treatment of cell lysates with acidic KMnO(4) solution. The basal amounts of iron
      in untreated astrocyte cultures were approximately 10 nmol iron per mg protein.
      Incubation of the cells with ferric ammonium citrate caused the total cellular
      iron content to increase in a concentration-dependent manner. The estimates of
      cellular iron content that were obtained with the ferrozine-based assay did not
      differ from those determined by atomic absorption spectroscopy. The colorimetric
      assay described here provides a sensitive, cheap, and reliable method for the
      quantitation of intracellular iron and for the investigation of iron accumulation
      in cultured cells.

PMID- 15265745
TI  - Quantification of streptavidin adsorption in microtitration wells.
AB  - Streptavidin-coated microtitration plates have an important role as a solid phase
      in clinical diagnostics. We have designed techniques for evaluating quantitative
      and functional aspects of streptavidin adsorbed in microtitration wells. The
      theoretical monolayer adsorption capacity was modeled based on the molecular
      dimensions of the protein. Adsorbed streptavidin was quantified by direct
      labeling of protein with terbium chelate and with a sensitive bicinchoninic acid
      based protein assay. A new small molecular weight (1037Da) reporter molecule, a
      europium-labeled biotin (Eu-biotin), was synthesized and used for monitoring
      adsorption and for determination of biotin-binding capacities of the streptavidin
      coated wells. The theoretical monolayer adsorption of streptavidin yielded 6.20
      pmol/cm(2) (370 ng) and consequently the theoretical adsorption capacity of a C12
      format microtitration well (200 microl liquid, coated area 1.54 cm(2)) was 9.55
      pmol/well (570 ng). Adsorption properties of streptavidin from two suppliers were
      tested, one of which yielded 350-380 ng/well while the other yielded over 500
      ng/well. The biotin binding capacities were about 11 and 14 pmol/well,
      respectively. We managed to quantify surface-adsorbed streptavidin with sensitive
      fluorescence and protein measurement methods in the microtitration well. The new
      Eu-biotin reporter molecule enabled an exact and convenient determination of the
      biotin-binding capacities of streptavidin surfaces.

PMID- 15265747
TI  - Protein molecular weight standards can compensate systematic errors in diffusion
      ordered spectroscopy.

PMID- 15265746
TI  - Binding of cationic liposomes to apoptotic cells.
AB  - One of the most prominent hallmarks of apoptotic cells is the altered
      characteristics of their plasma membrane, with its blebbing and exposure of the
      anionic phospholipid, phosphatidylserine (PS), in the outer leaflet of the lipid
      bilayer. The latter feature provides the basis of distinguishing apoptotic cells
      from most normal cells due to staining with fluorescently labeled annexin V,
      binding specifically to PS. In this article, we report on the binding to
      apoptotic leukemic T cells (Jurkat cell line, treated with different apoptotic
      inducers) of cationic liposomes (CLs) composed of the cationic gemini surfactant
      SS-1 ((2S,3S)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane
      dibromide), the fluorescent lipid analog DOPRho (1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-N-(lissamine rhodamine B sulfonyl)), and POPC (1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine). Control cells showed negligible and
      irregular binding patterns of CLs, whereas apoptotic cells revealed a strongly
      augmented staining of their plasma membrane. Morphological observations and
      comparison with standard procedures for detecting apoptotic cells further
      demonstrated the binding of CLs to be intense for cells undergoing apoptosis. In
      addition, some apoptotic cells with higher caspase-3 activity also revealed more
      pronounced staining by CLs. Our data suggest that the binding of CLs to apoptotic
      cells is mediated through an electrostatic interaction between the positively
      charged head group of SS-1 and the translocated anionic phospholipid PS in the
      plasma membrane. Because the fluorescent lipid tracer can be freely selected,
      this approach provides convenient and versatile means for the fluorescence
      detection of apoptotic cells.

PMID- 15265748
TI  - L-alanine-p-nitroanilide is not a substrate for VanX.

PMID- 15265749
TI  - An improvement of the site-directed mutagenesis method by combination of
      megaprimer, one-side PCR and DpnI treatment.

PMID- 15265750
TI  - Rapid and efficient polymerase chain reaction-based strategies for one-site and
      two-site mutagenesis.

PMID- 15265751
TI  - Primary sources of health information: comparisons in the domain of health
      attitudes, health cognitions, and health behaviors.
AB  - The recent growth in consumer autonomy in health care accompanied by the surge in
      the use of new media for health information gathering has led to an increasing
      scholarly interest in understanding the consumer health information search
      construct. This article explores consumer health information seeking in the realm
      of the primary sources of health information used by consumers. Based on an
      analysis of the 1999 HealthStyles data, the paper demonstrates that active
      communication channels such as interpersonal communication, print readership, and
      Internet communication serve as primary health information sources for health
      conscious, health-information oriented individuals with strong health beliefs,
      and commitment to healthy activities. On the other hand, passive consumption
      channels such as television and radio serve as primary health information
      resources for individuals who are not health-oriented. Media planning
      implications are drawn from the results, suggesting that broadcast outlets with
      an entertainment orientation are better suited for prevention campaigns. Such
      channels provide suitable sites for entertainment-education. On the other hand,
      print media, interpersonal networks, and the Internet are better suited for
      communicating about health issues to the health-active consumer segment.

PMID- 15265752
TI  - Physicians' and patients' perceptions of patients' communication competence in a
      primary care medical interview.
AB  - Considerable research suggests that patients and physicians often perceive
      aspects of the medical interview quite differently. Despite extensive research
      into physician-patient communication, virtually no attention has been given to
      assessing patients' and physicians' perceptions of communication competence
      during the medical interview. The purpose of this research was to determine the
      extent of agreement between physicians and patients on what behaviors constitute
      competent patient communication. The results indicate that there is considerable
      agreement between physicians and patients on the categories of competent patient
      communication. However, there is little or no evidence for agreement at the
      dyadic level on the occurrence of competent patient communication. Moreover,
      there is little evidence that physicians' and patients' perceptions of competence
      correlate with patients' actual discourse. These results are discussed with
      respect to implications for future research on patient communication skills
      training interventions.

PMID- 15265753
TI  - Social support and the management of uncertainty for people living with HIV or
      AIDS.
AB  - People with chronic and acute illnesses experience uncertainty about their
      prognoses, potential treatments, social relationships, and identity concerns. In
      a focus group study of people living with HIV or AIDS, we examined how social
      support may facilitate or interfere with the management of uncertainty about
      health, identity, and relationships. We found that support from others helps
      people with HIV or AIDS to manage uncertainty by (a) assisting with information
      seeking and avoiding, (b) providing instrumental support, (c) facilitating skill
      development, (d) giving acceptance or validation, (e) allowing ventilation, and
      (f) encouraging perspective shifts. Respondents also reported a variety of ways
      in which supportive others interfered with uncertainty management or in which
      seeking support imposed costs. Problems associated with social support and
      uncertainty management included a lack of coordination in uncertainty management
      assistance, the addition of relational uncertainty to illness uncertainty, and
      the burden of others' uncertainty management. Our study reveals strategies
      respondents used to manage costs and complications of receiving support,
      including developing an active or self-advocating orientation, reframing
      supportive interactions, withdrawing from nonproductive social situations,
      selectively allowing others to be support persons, and maintaining boundaries.

PMID- 15265754
TI  - Encouraging family discussion on the decision to donate organs: the role of the
      willingness to communicate scale.
AB  - Family discussion of organ donation has been found to double rates of family
      consent regarding organ donation. Therefore, family discussion is an important
      communication process to study in the effort to get more people to become organ
      donors. This investigation concerns the willingness to communicate about organ
      donation and its relationship to other variables and processes related to family
      discussion of organ donation. Previous research on willingness to communicate
      examined the antecedent variables of knowledge, attitude toward organ donation,
      and altruism. This research found that being willing to communicate about organ
      donation with one's family is related to prior thought and intent to sign an
      organ donor card, to perceiving organ donation messages as credible, and to
      feeling relatively low anxiety after reading organ donation messages. One week
      after being presented with the messages, willingness to communicate was found to
      be positively associated with worrying about the lack of donors, engaging in
      family discussion about organ donation, and having an organ donor card witnessed.
      It was negatively related to feeling personally uneasy about organ donation
      during the past week.

PMID- 15265755
TI  - Stressors and social support perceptions predict illness attitudes and care
      seeking intentions: re-examining the sick role.
AB  - Parsons' (1951) sick role concept has had a profound impact on the study of
      sickness as a social phenomenon. The sick role might be better conceived as a set
      of illness attitudes and care-seeking intentions rather than a set of social
      norms. This investigation purports (a) to explore the relationships among illness
      attitudes, (b) to examine the ability of illness attitudes to predict medical
      care-seeking intentions, and (c) to investigate differences in the sick role as a
      function of stressors and social support perceptions. Participants (N = 148)
      completed a survey questionnaire assessing daily hassles, life events, perceived
      social support, dependence, self-criticism, and the sick role. Results of a
      factor analysis on the sick role measures revealed four attitudinal (Release,
      Consideration, Burden, and Deviance) and two behavioral (Denial and Consult)
      factors. The attitudinal factors were moderately intercorrelated, with some
      ability to predict care-seeking intentions. Regression analyses revealed that
      stressors and support perceptions did exhibit some ability to predict the sick
      role. Results are discussed in terms of their implications for health
      communication research.

PMID- 15265756
TI  - Perceptions of health care providers' communication: relationships between
      patient-centered communication and satisfaction.
AB  - Specific communication practices of multiple professionals in health care
      settings can impact patient outcomes. This study, conducted at a large Children's
      Hospital, sought to determine the extent to which patient-centered communication
      (PCC) affected satisfaction with communication and with care itself. Parents of
      child patients (N = 195) reported on the communication practices of physicians,
      nurses, and hospital staff members during their most recent stay in the hospital.
      Surveys were completed on site. Health care providers' use of PCC behaviors,
      especially immediacy and perceived listening, was positively associated with
      satisfaction with care and with communication. In addition, PCC behaviors were
      perceived to be used more frequently with children in better health than with
      children with poorer health status.

PMID- 15265758
TI  - Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by
      ameliorating mitochondrial metabolism.
AB  - A low-taurine diet during fetal or early postnatal life causes abnormal
      pancreatic beta-cell development. Tissue and plasma taurine concentrations can
      also be low in diabetic patients. We examined the effect of taurine on impaired
      glucose responses in diabetic rat beta-cells adenovirally overexpressing
      uncoupling protein (UCP)2, which is upregulated in obesity-related type 2
      diabetes. We found that taurine pretreatment restored the ATP-to-ADP (ATP/ADP)
      ratio and glucose-stimulated insulin secretion in UCP2-infected islets. ATP
      sensitive K(+) channel sensitivity to dihydroxyacetone, another insulin
      secretagogue, was similar in both UCP2-infected and control beta-cells. In
      freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1
      beta-cells, methyl pyruvate-mediated mitochondrial Ca(2+) increase was
      significantly ameliorated by taurine. A mitochondrial Ca(2+) uniporter blocker,
      ruthenium red, inhibited the action of taurine. This study suggests that taurine
      enhances the glucose sensitivity of UCP2-overexpressing beta-cells, probably by
      increasing mitochondrial Ca(2+) influx through the Ca(2+) uniporter, thereby
      enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.

PMID- 15265759
TI  - Tetrahydrobiopterin increases insulin sensitivity in patients with type 2
      diabetes and coronary heart disease.
AB  - Tetrahydrobiopterin (BH(4)) is an essential cofactor of nitric oxide synthase
      that improves endothelial function in diabetics, smokers, and patients with
      hypercholesterolemia. Insulin resistance has been suggested as a contributing
      factor in the development of endothelial dysfunction via an abnormal pteridine
      metabolism. We hypothesized that BH(4) would restore flow-mediated vasodilation
      (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in
      type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10
      matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent
      infusion of BH(4) or saline in a random crossover study. Insulin sensitivity
      index (S(I)) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured
      using ultrasonography. BH(4) significantly increased S(I) in the type 2 diabetics
      [3.6 +/- 0.6 vs. 4.9 +/- 0.7 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P < 0.05],
      while having no effects in nondiabetics [8.9 +/- 1.1 vs. 9.0 +/- 0.9 x 10(-4)
      dl.kg(-1).min(-1)/(microU/ml), P = 0.92] or in healthy subjects [17.5 +/- 1.6 vs.
      18 +/- 1.8 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.87]. BH(4) did not
      affect the relative changes in brachial artery diameter from baseline FMD (%) in
      type 2 diabetic subjects (2.3 +/- 0.8 vs. 1.8 +/- 1.0%, P = 0.42), nondiabetic
      subjects (5.3 +/- 1.1 vs. 6.6 +/- 0.9%, P = 0.32), or healthy subjects (11.9 +/-
      0.6 vs. 11.0 +/- 1.0%, P = 0.48). In conclusion, BH(4) significantly increases
      insulin sensitivity in type 2 diabetic patients without any discernible
      improvement in endothelial function.

PMID- 15265760
TI  - AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in
      vivo.
AB  - AMP-activated protein kinase (AMPK) independently increases glucose and long
      chain fatty acid (LCFA) utilization in isolated cardiac muscle preparations.
      Recent studies indicate this may be due to AMPK-induced phosphorylation and
      activation of nitric oxide synthase (NOS). Given this, the aim of the present
      study was to assess the effects of AMPK stimulation by 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR; 10 mg.kg(-1).min(-1)) on glucose and
      LCFA utilization in cardiac muscle and to determine the NOS dependence of any
      observed effects. Catheters were chronically implanted in a carotid artery and
      jugular vein of Sprague-Dawley rats. After 4 days of recovery, conscious,
      unrestrained rats were given either water or water containing 1 mg/ml nitro-L
      arginine methyl ester (L-NAME) for 2.5 days. After an overnight fast, rats
      underwent one of four protocols: saline, AICAR, AICAR + L-NAME, or AICAR +
      Intralipid (20%, 0.02 ml.kg(-1).min(-1)). Glucose was clamped at approximately
      6.5 mM in all groups, and an intravenous bolus of 2-deoxy-[(3)H]glucose and
      [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid was administered to
      obtain indexes of glucose and LCFA uptake and clearance. Despite AMPK activation,
      as evidenced by acetyl-CoA carboxylase (Ser(221)) and AMPK phosphorylation
      (Thr(172)), AICAR increased cardiac LCFA but not glucose clearance. L-NAME +
      AICAR established that this effect was not due to NOS activation, and AICAR +
      Intralipid showed that increased cardiac LCFA clearance was not LCFA
      concentration dependent. These results demonstrate that, in vivo, AMPK
      stimulation increases LCFA but not glucose clearance by a NOS-independent
      mechanism.

PMID- 15265761
TI  - Gonadotropin-releasing hormone and TGF-beta activate MAP kinase and
      differentially regulate fibronectin expression in endometrial epithelial and
      stromal cells.
AB  - Gonadotropin-releasing hormone analog (GnRHa) is used for medical management of
      endometriosis and premature luteinizing hormone surge during controlled ovarian
      stimulation. Human endometrium expresses GnRH receptors, and GnRHa alters the
      expression of transforming growth factor-beta (TGF-beta) and receptors in
      endometrial cells. Because the diverse biological actions of GnRHa and TGF-beta
      are mediated in part through the MAPK pathway, we determined whether utilization
      of MAPK/ERK and transcriptional activation of immediate early genes c-fos and c
      jun result in differential regulation of fibronectin, known as key regulator of
      embryo implantation and endometriosis progression. Using endometrial stromal
      cells (ESC) and the endometrial epithelial cell line HES, we demonstrated that
      GnRHa and TGF-beta, in a dose-, time-, and cell-dependent manner, increased the
      level of phosphorylated ERK1/2 (pERK1/2). GnRH antagonist Antide also increased
      pERK1/2 induction in ESC and HES, whereas pretreatment reduced GnRHa-induced
      pERK2 in ESC but not in HES. Cotreatments with GnRHa plus TGF-beta1 did not have
      an additive or an inhibitory effect on pERK1/2 induction compared with GnRHa or
      TGF-beta1 action alone. TGF-beta1 and GnRHa increased ERK1/2 nuclear accumulation
      and inversely regulated the expression of c-fos and c-jun and that of fibronectin
      in a cell-specific manner. Pretreatment with U-0126, a MEK1/2 inhibitor, blocked
      basal, as well as GnRHa- and TGF-beta1-induced pERK1/2; however, it
      differentially affected c-fos, c-jun, and fibronectin expression. In conclusion,
      the results indicate that GnRHa and TGF-beta signaling through MAPK/ERK results
      in differential regulation of fibronectin expression in endometrial cells, a
      molecular mechanism where short- and long-term GnRHa therapy and locally
      expressed TGF-beta could influence embryo implantation and endometriosis
      implants, respectively.

PMID- 15265762
TI  - Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4
      translocation in heart muscle.
AB  - AMP-activated protein kinase (AMPK) is a serine-threonine kinase that regulates
      cellular metabolism and has an essential role in activating glucose transport
      during hypoxia and ischemia. The mechanisms responsible for AMPK stimulation of
      glucose transport are uncertain, but may involve interaction with other signaling
      pathways or direct effects on GLUT vesicular trafficking. One potential
      downstream mediator of AMPK signaling is the nitric oxide pathway. The aim of
      this study was to examine the extent to which AMPK mediates glucose transport
      through activation of the nitric oxide (NO)-signaling pathway in isolated heart
      muscles. Incubation with 1 mM 5-amino-4-imidazole-1-beta-carboxamide
      ribofuranoside (AICAR) activated AMPK (P < 0.01) and stimulated glucose uptake (P
      < 0.05) and translocation of the cardiomyocyte glucose transporter GLUT4 to the
      cell surface (P < 0.05). AICAR treatment increased phosphorylation of endothelial
      NO synthase (eNOS) approximately 1.8-fold (P < 0.05). eNOS, but not neuronal NOS,
      coimmunoprecipitated with both the alpha(2) and alpha(1) AMPK catalytic subunits
      in heart muscle. NO donors also increased glucose uptake and GLUT4 translocation
      (P < 0.05). Inhibition of NOS with N(omega)-nitro-l-arginine and N(omega)-methyl
      l-arginine reduced AICAR-stimulated glucose uptake by 21 +/- 3% (P < 0.05) and 25
      +/- 4% (P < 0.05), respectively. Inhibition of guanylate cyclase with ODQ and LY
      83583 reduced AICAR-stimulated glucose uptake by 31 +/- 4% (P < 0.05) and 22 +/-
      3% (P < 0.05), respectively, as well as GLUT4 translocation to the cell surface
      (P < 0.05). Taken together, these results indicate that activation of the NO
      guanylate cyclase pathway contributes to, but is not the sole mediator of, AMPK
      stimulation of glucose uptake and GLUT4 translocation in heart muscle.

PMID- 15265764
TI  - Time course of nitric oxide production after endotoxin challenge in mice.
AB  - Nitric oxide (NO) regulates numerous processes during endotoxemia and
      inflammation. However, the sequential changes in whole body (Wb) nitric oxide
      (NO) production during endotoxemia in vivo remain to be clarified. Male Swiss
      mice were injected intraperitoneally with saline (control group) or
      lipopolysaccharide (LPS group). After 0, 2, 4, 6, 9, 12, and 24 h, animals
      received a primed constant infusion of L-[guanidino-(15)N(2)-(2)H(2)]arginine, L
      [ureido-(15)N]citrulline, L-[5-(15)N]glutamine, and L-[ring-(2)H(5)]phenylalanine
      in the jugular vein. Arterial blood was collected for plasma arginine (Arg),
      citrulline (Cit), glutamine (Gln), and phenylalanine (Phe) concentrations and
      tracer-to-tracee ratios. NO production was calculated as plasma Arg-to-Cit flux,
      Wb de novo Arg synthesis as plasma Cit-to-Arg flux, and Wb protein breakdown as
      plasma Phe flux. LPS reduced plasma Arg and Cit and increased Gln and Phe
      concentrations. Two peaks of NO production were observed at 4 and 12 h after LPS.
      Although LPS did not affect total Arg production, de novo Arg production
      decreased after 12 h. The second peak of NO production coincided with increased
      Wb Cit, Gln, and Phe production. In conclusion, the curve of NO production in
      both early and late phases of endotoxemia is not related to plasma Arg kinetics.
      However, because Wb Cit, Gln, and Phe fluxes increased concomitantly with the
      second peak of NO production, NO production is probably related to the catabolic
      phase of endotoxemia.

PMID- 15265763
TI  - Glutamine kinetics and protein turnover in end-stage renal disease.
AB  - Alanine and glutamine constitute the two most important nitrogen carriers
      released from the muscle. We studied the intracellular amino acid transport
      kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and
      eight controls by use of stable isotopes of phenylalanine, alanine, and
      glutamine. The amino acid transport kinetics and protein turnover were calculated
      with a three-pool model from the amino acid concentrations and enrichment in the
      artery, vein, and muscle compartments. Muscle protein breakdown was more than
      synthesis (nmol.min(-1).100 ml leg(-1)) during hemodialysis (HD) (169.8 +/- 20.0
      vs. 125.9 +/- 21.8, P < 0.05) and in controls (126.9 +/- 6.9 vs. 98.4 +/- 7.5, P
      < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 +/- 15.7 vs.
      103.4 +/- 14.8). Whole body protein catabolism decreased by 15% during HD. The
      intracellular appearance of alanine (399.0 +/- 47.1 vs. 243.0 +/- 34.689) and
      glutamine (369.7 +/- 40.6 vs. 235.6 +/- 27.5) from muscle protein breakdown
      increased during dialysis (nmol.min(-1).100 ml leg(-1), P < 0.01). However, the
      de novo synthesis of alanine (3,468.9 +/- 572.2 vs. 3,140.5 +/- 467.7) and
      glutamine (1,751.4 +/- 82.6 vs. 1,782.2 +/- 86.4) did not change significantly
      intradialysis (nmol.min(-1).100 ml leg(-1)). Branched-chain amino acid catabolism
      (191.8 +/- 63.4 vs. -59.1 +/- 42.9) and nonprotein glutamate disposal (347.0 +/-
      46.3 vs. 222.3 +/- 43.6) increased intradialysis compared with pre-HD (nmol.min(
      1).100 ml leg(-1), P < 0.01). The mRNA levels of glutamine synthase (1.45 +/-
      0.14 vs. 0.33 +/- 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2
      (3.86 +/- 0.48 vs. 2.14 +/- 0.27, P < 0.05) in the muscle increased during HD.
      Thus intracellular concentrations of alanine and glutamine are maintained during
      HD by augmented release of the amino acids from muscle protein catabolism.
      Although muscle protein breakdown increased intradialysis, the whole body protein
      catabolism decreased, suggesting central utilization of amino acids released from
      skeletal muscle.

PMID- 15265765
TI  - Dopamine recruits D1A receptors to Na-K-ATPase-rich caveolar plasma membranes in
      rat renal proximal tubules.
AB  - Activation of dopamine D(1A) receptors in renal proximal tubules causes
      inhibition of sodium transporters (Na-K-ATPase and Na/H exchanger), leading to a
      decrease in sodium reabsorption. In addition to being localized on the plasma
      membrane, D(1A) receptors are mainly present in intracellular compartments under
      basal conditions. We observed, using [(3)H]SCH-23390 binding and immunoblotting,
      that dopamine recruits D(1A) receptors to the plasma membrane in rat renal
      proximal tubules. Furthermore, radioligand binding and/or immunoblotting
      experiments using pharmacological modulators showed that dopamine-induced D(1A)
      receptor recruitment requires activation of cell surface D(1)-like receptors,
      activation of adenylyl cyclase, and intact endocytic vesicles with internal
      acidic pH. A key finding of this study was that these recruited D(1A) receptors
      were functional because they potentiated dopamine-induced [(35)S]GTPgammaS
      binding, cAMP accumulation, and Na-K-ATPase inhibition. Interestingly, dopamine
      increased immunoreactivity of D(1A) receptors specifically in caveolin-rich
      plasma membranes isolated by a sucrose density gradient. In support of this
      observation, coimmunoprecipitation studies showed that D(1A) receptors interacted
      with caveolin-2 in an agonist-dependent fashion. The caveolin-rich plasma
      membranes had a high content of the alpha(1)-subunit of Na-K-ATPase, which is a
      downstream target of D(1A) receptor signaling in proximal tubules. These results
      show that dopamine, via the D(1)-like receptor-adenylyl cyclase pathway, recruits
      D(1A) receptors to the plasma membrane. These newly recruited receptors couple to
      G proteins, increase cAMP, and participate in dopamine-mediated inhibition of Na
      K-ATPase in proximal tubules. Moreover, dopamine-induced recruitment of D(1A)
      receptors to the caveolin-rich plasma membranes brings them in close proximity to
      targets such as Na-K-ATPase in proximal tubules of Sprague-Dawley rats.

PMID- 15265766
TI  - Gialpha3 protein-coupled dopamine D3 receptor-mediated inhibition of renal NHE3
      activity in SHR proximal tubular cells is a PLC-PKC-mediated event.
AB  - This study evaluated the transduction pathway associated with type 3 Na(+)/H(+)
      exchanger (NHE3) activity-induced inhibition during dopamine D(3) receptor
      activation in immortalized renal proximal tubular epithelial cells from the
      spontaneously hypertensive rat. The dopamine D(3) receptor agonist 7-OH-DPAT
      decreased NHE3 activity, which was prevented by the D(2)-like receptor antagonist
      S-sulpiride, pertussis toxin (PTX; overnight treatment), and the PKC inhibitor
      chelerythrine, but not by cholera toxin (overnight treatment), the MAPK inhibitor
      PD-098059, or the p38 inhibitor SB-203580. The PKA inhibitor H-89 abolished the
      inhibitory effects of forskolin on NHE3 activity, but not that of 7-OH-DPAT. The
      phospholipase C (PLC) inhibitor U-73122 prevented the inhibitory effects of 7-OH
      DPAT, whereas PDBu and 7-OH-DPAT increased PLC activity and reduced NHE3
      activity; downregulation of PKC abolished the inhibitory effects of both PDBu and
      7-OH-DPAT on NHE activity. The inhibition of NHE3 activity by GTPgammaS and the
      prevention of the effect of 7-OH-DPAT by PTX suggest an involvement of a G(i/o)
      protein coupled to the dopamine D(3) receptor. Indeed, the 7-OH-DPAT-induced
      decrease in NHE3 activity was abolished in cells treated overnight with the anti
      G(i)alpha3 antibody, but not in cells treated with antibodies against G(q/11),
      G(s)alpha, G(beta), and G(i)alpha1,2 proteins. The calcium ionophore A-23187 and
      the Ca(2+)-ATPase inhibitor thapsigargin increased intracellular Ca(2+) but did
      not affect NHE3 activity. However, the inhibitory effects of PDBu and 7-OH-DPAT
      on NHE3 activity were completely abolished by A-23287 and thapsigargin. It is
      concluded that inhibition of NHE3 activity by dopamine D(3) receptors coupled to
      G(i)alpha3 proteins is a PLC-PKC-mediated event, modulated by intracellular
      Ca(2+).

PMID- 15265767
TI  - Differential traffic of proximal tubule Na+ transporters during hypertension or
      PTH: NHE3 to base of microvilli vs. NaPi2 to endosomes.
AB  - We previously reported that Na(+)/H(+) exchanger type 3 (NHE3) and NaPi2 are
      acutely retracted from the proximal tubule (PT) microvilli (MV) during acute
      hypertension [high blood pressure (BP)] or parathyroid hormone (PTH) treatment.
      By subcellular membrane fractionation, NHE3 and NaPi2 show indistinguishable
      redistribution patterns out of light-density into heavy-density membranes in
      response to either treatment consistent with a retraction from the apical MV to
      the intermicrovillar cleft region. This study aimed to examine the redistribution
      of PT NHE3 vs. NaPi2 by confocal and electron microscopy during high BP and
      during PTH treatment to determine whether their respective destinations overlap
      or are distinct. High-BP protocol: systolic BP was increased 50-60 mmHg by
      increasing peripheral resistance for 20 min; PTH protocol: rats were infused with
      6.6 microg/kg iv of PTH followed by 0.1 microg.kg(-1).min(-1) infusion for 1 h.
      For light microscopy, rats were infused with 25 mg of horseradish peroxidase
      (HRP) 10 min before kidney fixation. Kidney slices were dual labeled with either
      NHE3 or NaPi2 and either clathrin-coated vesicle adaptor protein AP2 or endosome
      marker HRP. The results demonstrate retraction of NHE3 from the MV to the base of
      MV during either high-BP or PTH treatment: NHE3 staining did not retract below
      the AP2-stained domain or to HRP-labeled endosomes in either model. In
      comparison, NaPi2 was retracted from MV to below the AP2-stained region in both
      models, a little colocalizing with HRP staining. At the electron microscopic
      level with immunogold labeling, during high BP NHE3 was concentrated in a
      distinct domain in the base of the MV while NaPi2 moved to endosomes. The results
      demonstrate that there are divergent routes of retraction of PT NHE3 and NaPi2
      from the MV during acute hypertension or PTH treatment: NHE3 is not internalized
      but remains at the base of the MV while NaPi2 is internalized.

PMID- 15265768
TI  - Dietary K intake regulates the response of apical K channels to adenosine in the
      thick ascending limb.
AB  - We used the patch-clamp technique to study the effect of adenosine on the apical
      70-pS K channel in the thick ascending limb (TAL) of the rat kidney. Application
      of 1 microM cyclohexyladenosine (CHA), an adenosine analog, stimulated apical 70
      pS K channel activity and increased the product of channel open probability and
      channel number (NP(o)) from 0.34 to 0.7. Also, addition of CGS-21680, a specific
      A(2a) adenosine receptor agonist, mimicked the effect of CHA and increased NP(o)
      from 0.33 to 0.77. The stimulatory effect of CHA and CGS-21680 was completely
      blocked by H89, an inhibitor of protein kinase A (PKA), or by inhibition of
      adenylate cyclase with SQ-22536. This suggests that the stimulatory effect of
      adenosine analogs is mediated by a PKA-dependent pathway. The effect of adenosine
      analog was almost absent in the TAL from rats on a K-deficient (KD) diet for 7
      days. Application of DDMS, an agent that inhibits cytochrome P-450 hydrolase, not
      only significantly increased the activity of the 70-pS K channel but also
      restored the stimulatory effect of CHA on the 70-pS K channel in the TAL from
      rats on a KD diet. Also, the effect of CHA was absent in the presence of 20-HETE.
      Inhibition of PKA blocked the stimulatory effect of CHA on the apical 70-pS K
      channel in the presence of DDMS in the TAL from rats on a KD diet. We conclude
      that stimulation of adenosine receptor increases the apical 70-pS K channel
      activity via a PKA-dependent pathway and that the effect of adenosine on the
      apical 70-pS K channel is suppressed by low-K intake. Moreover, the diminished
      response to adenosine is the result of increase in 20-HETE formation, which
      inhibits the cAMP-dependent pathway in the TAL from rats on a KD diet.

PMID- 15265769
TI  - Effect of thiazide on renal gene expression of apical calcium channels and
      calbindins.
AB  - Thiazide diuretics are specific inhibitors of the Na-Cl cotransporter in the
      distal convoluted tubule (DCT). In addition to producing diuresis and
      natriuresis, they have a hypocalciuric effect. Recently, two apical calcium
      channels have been identified, transient receptor potential vanilloid 5 (TRPV5)
      and TRPV6; both are expressed in the DCT. We studied the effects of thiazides on
      mouse renal calcium handling and renal gene expression of TRPV5 and TRPV6, as
      well as calbindin-D(28k) and calbindin-D(9k), both of which are calcium transport
      facilitators located in the DCT. Upregulation of renal TRPV5 was found 4 h after
      intraperitoneal injection of chlorothiazide (CTZ) at both 25 and 50 mg/kg, but
      not at 100 mg/kg. Chronic treatment with CTZ at 25 mg/kg twice daily for 3 days,
      with or without salt supplementation of 0.8% NaCl and 0.1% KCl in the drinking
      water, caused hypocalciuria, but the gene expression patterns were different.
      Without salt supplementation, mice developed volume contraction and there were no
      changes in gene expression. When volume contraction was prevented by salt
      supplementation, there was a significant increase in gene expression of TRPV5,
      calbindin-D(28k), and calbindin-D(9k). Salt supplementation alone also induced
      significant upregulation of TRPV5, TRPV6, and both calbindins. The upregulation
      of TRPV5 by CTZ and salt supplementation and salt alone was further confirmed
      with immunofluorescent staining studies. Our studies suggest that thiazides
      induce hypocalciuria through different mechanisms depending on volume status.
      With volume contraction, increased calcium reabsorption in the proximal tubule
      plays the major role. Without volume contraction, hypocalciuria is probably
      achieved through increased calcium reabsorption in the DCT by the activation of a
      transcellular calcium transport system and upregulation of apical calcium channel
      TRPV5, calbindin-D(28k), and calbindin-D(9k).

PMID- 15265770
TI  - Glucocorticoids and their actions: an introduction.

PMID- 15265771
TI  - Novel repression of the glucocorticoid receptor by anthrax lethal toxin.
AB  - Death from anthrax has been reported to occur from systemic shock. The lethal
      toxin (LeTx) is the major effector of anthrax mortality. Although the mechanism
      of entry of this toxin into cells is well understood, its actions once inside the
      cell are not as well understood. LeTx is known to cleave and inactivate MAPKKs.
      We have recently shown that LeTx represses the glucocorticoid receptor (GR) both
      in vitro and in vivo. This repression is partial and specific, repressing the
      glucocorticoid, progesterone, and estrogen receptor alpha, but not the
      mineralocorticoid or estrogen receptor beta. This toxin does not affect GR ligand
      or DNA binding, and we have suggested that it may function by
      removing/inactivating one or more of the many cofactors involved in nuclear
      hormone receptor signaling. Although the precise involvement of this nuclear
      hormone receptor repression in LeTx toxicity is unknown, examples of blunted HPA
      axis and glucocorticoid signaling in numerous autoimmune/inflammatory diseases
      suggest that such repression of critically important receptors could have
      deleterious effects on health.

PMID- 15265772
TI  - Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS.
AB  - Dysregulated systemic inflammation with excess activation of pro-inflammatory
      transcription factor nuclear factor-kappaB (NF-kappaB)-activated by inflammatory
      signals-compared to the anti-inflammatory transcription factor glucocorticoid
      receptor-alpha (GRalpha)-activated by endogenous or exogenous glucocorticoids
      (GCs)-is an important pathogenetic mechanism for pulmonary and extrapulmonary
      organ dysfunction in patients with acute respiratory distress syndrome (ARDS).
      Activation of one transcription factor in excess of the binding (inhibitory)
      capacity of the other shifts cellular responses toward increased (dysregulated)
      or decreased (regulated) transcription of inflammatory mediators over time.
      Recent data indicate that failure to improve in ARDS (unresolving ARDS) is
      frequently associated with failure of the activated GRs to downregulate the
      transcription of inflammatory cytokines despite elevated levels of circulating
      cortisol, a condition defined as systemic inflammation-associated acquired GC
      resistance; it is potentially reversible with prolonged GC supplementation. In
      the first part of this paper, after a brief description of inflammation in ARDS
      and our model of translational research, we review the two cellular signaling
      pathways that are central to the regulation of inflammation-the stimulatory NF
      alphaB and the inhibitory GRalpha. In the second part, we review findings of
      recent studies indicating that excessive inflammatory activity in patients with
      unresolving ARDS may induce noncompensated GC resistance in target organs. In the
      third part, we review factors affecting cellular response to GC and potential
      mechanisms involved in inflammation-associated GC resistance.

PMID- 15265773
TI  - Physiological and pathological consequences of the interactions of the p53 tumor
      suppressor with the glucocorticoid, androgen, and estrogen receptors.
AB  - The p53 tumor suppressor plays a key role in protection from the effects of
      different physiological stresses (DNA damage, hypoxia, transcriptional defects,
      etc.), and loss of its activity has dire consequences, such as cancer. Its
      activity is finely tuned through interactions with other important regulatory
      circuits in the cell. Recently, striking evidence has emerged for crosstalk with
      another class of important regulators, the steroid hormone receptors, and in
      particular the glucocorticoid (GR), androgen (AR), and estrogen (ER) receptors.
      These receptors are important in maintaining homeostasis in response to internal
      and external stresses (GR) and in the development, growth, and maintenance of the
      male and female reproductive systems (AR and ER, respectively). We review how p53
      interacts closely with these receptors, to the extent that they share the same E3
      ubiquitin ligase, the MDM2 oncoprotein. We discuss the different physiological
      contexts in which such interactions occur, and also how these interactions have
      been undermined in various pathological situations. We will describe future areas
      for research, with special emphasis on GR, and how certain common features, such
      as cytoplasmic anchoring of p53 by the receptors, may become targets for the
      development of therapeutic interventions. Given the importance of GR in
      inflammation, erythropoiesis, and autoimmune diseases, and the importance of AR
      and ER in prostate and breast cancer (respectively), the studies on p53
      interactions with the steroid receptors will be an important domain in the near
      future.

PMID- 15265774
TI  - Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream
      promoter-transcription factor II (COUP-TFII): implications for the actions of
      glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism.
AB  - Glucocorticoids exert their extremely diverse effects on numerous biologic
      activities of humans via only one protein module, the glucocorticoid receptor
      (GR). The GR binds to the glucocorticoid response elements located in the
      promoter region of target genes and regulates their transcriptional activity. In
      addition, GR associates with other transcription factors through direct protein
      protein interactions and mutually represses or stimulates each other's
      transcriptional activities. The latter activity of GR may be more important than
      the former one, granted that mice harboring a mutant GR, which is active in terms
      of protein-protein interactions but inactive in terms of transactivation via DNA,
      survive and procreate, in contrast to mice with a deletion of the entire GR gene
      that die immediately after birth. We recently found that GR physically interacts
      with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII),
      which plays a critical role in the metabolism of glucose, cholesterol, and
      xenobiotics, as well as in the development of the central nervous system in
      fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors
      via its activation function-1, while COUP-TFII represses the GR-governed
      transcriptional activity by tethering corepressors, such as the silencing
      mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear
      receptor corepressors (NCoRs) via its C-terminal domain. Their mutual interaction
      may play an important role in gluconeogenesis, lipoprotein metabolism, and
      enzymatic clearance of clinically important compounds and bioactive chemicals, by
      regulating their rate-limiting enzymes and molecules, including the
      phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A,
      and several apolipoproteins. It appears that glucocorticoids exert their
      intermediary effects partly via physical interaction with COUP-TFII.

PMID- 15265775
TI  - Modulation of glucocorticoid receptor function via phosphorylation.
AB  - The glucocorticoid receptor (GR) is phosphorylated at multiple serine residues in
      a hormone-dependent manner. It has been suggested that GR phosphorylation affects
      turnover, subcellular trafficking, or the transcriptional regulatory functions of
      the receptor, yet the contribution of individual GR phosphorylation sites to the
      modulation of GR activity remains enigmatic. This review critically evaluates the
      literature on GR phosphorylation and presents more recent work on the mechanism
      of GR phosphorylation from studies using antibodies that recognize GR only when
      it is phosphorylated. In addition, we present support for the notion that GR
      phosphorylation modifies protein-protein interactions, which can stabilize the
      hypophosphorylated form of the receptor in the absence of ligand, as well as
      facilitate transcriptional activation by the hyperphosphorylation of GR via
      cofactor recruitment upon ligand binding. Finally, we propose that GR
      phosphorylation also participates in the nongenomic activation of cytoplasmic
      signaling pathways evoked by GR. Thus, GR phosphorylation is a versatile
      mechanism for modulating and integrating multiple receptor functions.

PMID- 15265776
TI  - The origin and functions of multiple human glucocorticoid receptor isoforms.
AB  - Glucocorticoid hormones are necessary for life and are essential in all aspects
      of human health and disease. The actions of glucocorticoids are mediated by the
      glucocorticoid receptor (GR), which binds glucocorticoid hormones and regulates
      gene expression, cell signaling, and homeostasis. Decades of research have
      focused on the mechanisms of action of one isoform of GR, GRa. However, in recent
      years, increasing numbers of human GR (hGR) isoforms have been reported. Evidence
      obtained from this and other laboratories indicates that multiple hGR isoforms
      are generated from one single hGR gene via mutations and/or polymorphisms,
      transcript alternative splicing, and alternative translation initiation. Each hGR
      protein, in turn, is subject to a variety of posttranslational modifications, and
      the nature and degree of posttranslational modification affect receptor function.
      We summarize here the processes that generate and modify various hGR isoforms
      with a focus on those that impact the ability of hGR to regulate target genes. We
      speculate that unique receptor compositions and relative receptor proportions
      within a cell determine the specific response to glucocorticoids. Unchecked
      expression of some isoforms, for example hGRbeta, has been implicated in various
      diseases.

PMID- 15265777
TI  - Overview of the actions of glucocorticoids on the immune response: a good model
      to characterize new pathways of immunosuppression for new treatment strategies.
AB  - Glucocorticoids have been used for over 50 years in the treatment of inflammatory
      and autoimmune diseases and in preventing graft rejection. Today, knowledge of
      their molecular, cellular, and pharmacological properties allows a better
      understanding of glucocorticoid-mediated immunosuppression. Glucocorticoids exert
      both negative and positive effects with a dynamic and bi-directional spectrum of
      activities on various limbs and components of the immune response. They modulate
      genes involved in the priming of the innate immune response, while their actions
      on the adaptive immune response are to suppress cellular (Th1) immunity and
      promote humoral (Th2) immunity. Interestingly, glucocorticoids can also induce
      tolerance to specific antigens by influencing dendritic cell maturation and
      function and promoting the development of regulatory high IL-10-producing T
      cells. The ex vivo therapeutic use of glucocorticoids could therefore represent
      an adjuvant treatment to cell therapy in autoimmune diseases, avoiding the long
      term deleterious adverse effects of glucocorticoids. Thus, the panoramic view of
      glucocorticoid actions on the immune system provides an interesting model for
      characterizing important biological pathways of immunosuppression.

PMID- 15265778
TI  - Glucocorticoids and the Th1/Th2 balance.
AB  - Evidence accumulated over the last 5-10 years indicates that glucocorticoids
      (GCs) inhibit the production of interleukin (IL)-12, interferon (IFN)-gamma, IFN
      alpha, and tumor necrosis factor (TNF)-alpha by antigen-presenting cells (APCs)
      and T helper (Th)1 cells, but upregulate the production of IL-4, IL-10, and IL-13
      by Th2 cells. Through this mechanism increased levels of GCs may systemically
      cause a selective suppression of the Th1-cellular immunity axis, and a shift
      toward Th2-mediated humoral immunity, rather than generalized immunosuppression.
      During an immune response and inflammation, the activation of the stress system,
      and thus increased levels of systemic GCs through induction of a Th2 shift, may
      actually protect the organism from systemic "overshooting" with Th1/pro
      inflammatory cytokines and other products of activated macrophages with tissue
      damaging potential. However, conditions associated with significant changes of
      GCs levels, such as acute or chronic stress or cessation of chronic stress,
      severe exercise, and pregnancy and postpartum, through modulation of the Th1/Th2
      balance may affect the susceptibility to or the course of infections as well as
      autoimmune and atopic/allergic diseases.

PMID- 15265779
TI  - L-Carnitine is a modulator of the glucocorticoid receptor alpha.
AB  - L-Carnitine (LC) is a nutrient with an essential role in cellular energy
      production. At high doses, LC can mimic some of the biological activities of
      glucocorticoids, particularly immunomodulation. To explore the molecular bases of
      this property, we tested the influence of LC on glucocorticoid receptor-a
      (GRalpha) functions. LC reduced the binding capacity of GRalpha, induced its
      nuclear translocation, and stimulated its transcriptional activity. Moreover, LC
      suppressed TNFalpha and IL-12 release from human monocytes in glucocorticoid-like
      fashion. We conclude that pharmacologic doses of LC can activate GRalpha and, via
      this mechanism, regulate glucocorticoid-responsive genes, potentially sharing
      some of the biological and therapeutic properties of glucocorticoids.

PMID- 15265780
TI  - Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of
      the AIDS-related insulin resistance/lipodystrophy syndrome?
AB  - Recent advances in the development of three different types of antiviral drugs,
      the nucleotide and non-nucleotide analogues acting as reverse transcriptase
      inhibitors (NRTIs) and the nonpeptidic viral protease inhibitors (PI), and their
      introduction in the management of patients with AIDS, either alone or in
      combination, have dramatically improved the clinical course of the disease and
      prolonged life expectancy in patients with AIDS. The increase in life expectancy
      in association with the long-term use of the above antiviral agents, however,
      have generated novel morbidities and complications. Central among them is the
      quite common AIDS-related insulin resistance and lipodystrophy syndrome, which is
      characterized by a striking phenotype and marked metabolic disturbances. To look
      for the pathologic causes of this particular syndrome, we focused on one of the
      HIV-1 accessory proteins, Vpr, which has multiple functions, such as virion
      incorporation, nuclear translocation of the HIV-1 preintegration complex, nucleo
      cytoplasmic shuttling, transcriptional activation, and induction of apoptosis.
      Vpr may also act like a hormone, which is secreted into the extracellular space
      and affects the function of distant organs. Vpr functions as a coactivator of the
      glucocorticoid receptor and potentiates the action of glucocorticoid hormones,
      thereby inducing tissue glucocorticoid hypersensitivity. Vpr also arrests host
      cells at the G2/M phase of the cell cycle by interacting with novel 14-3-3
      proteins. Vpr facilitates the interaction of 14-3-3 and its partner protein
      Cdc25C, which is critical for the transition of G2/M checkpoint in the cell
      cycle, and suppresses its activity by segregating it into the cytoplasm. The same
      Vpr protein also suppresses the association of 14-3-3 with other partner
      molecules, the Foxo transcription factors. Since the Foxo proteins function as
      negative transcription factors for insulin, Vpr may cause resistance of tissues
      to insulin. Through these two newly identified functions of Vpr, namely,
      coactivation of glucocorticoid receptor activity and inhibition of insulin
      effects on Foxo proteins, Vpr may participate in the development of AIDS-related
      insulin resistance/lipodystrophy syndrome.

PMID- 15265781
TI  - Familial/sporadic glucocorticoid resistance: clinical phenotype and molecular
      mechanisms.
AB  - Glucocorticoids regulate a variety of biologic processes and exert profound
      influences on many physiologic functions. Their actions are mediated by the
      glucocorticoid receptor (GR), which belongs to the nuclear receptor family of
      ligand-dependent transcription factors. Alterations in tissue sensitivity to
      glucocorticoids may manifest as states of resistance or hypersensitivity.
      Glucocorticoid resistance is a rare, familial or sporadic, condition
      characterized by generalized, partial target-tissue resistance to
      glucocorticoids. Compensatory elevations in circulating adrenocorticotropic
      hormone (ACTH) concentrations lead to increased production of adrenal steroids
      with mineralocorticoid and/or androgenic activity and their corresponding
      clinical manifestations, as well as increased urinary free-cortisol excretion in
      the absence of symptomatology suggestive of hypercortisolism. The molecular basis
      of the condition has been ascribed to mutations in the GR gene, which impair
      normal glucocorticoid signal transduction, altering tissue sensitivity to
      glucocorticoids. The present review focuses on the mechanisms of GR action and
      the clinical manifestations and molecular mechanisms of familial/sporadic
      glucocorticoid resistance.

PMID- 15265782
TI  - Early environmental regulation of hippocampal glucocorticoid receptor gene
      expression: characterization of intracellular mediators and potential genomic
      target sites.
AB  - Environmental conditions in early life permanently alter the development of
      glucocorticoid receptor gene expression in the hippocampus and hypothalamic
      pituitary-adrenal responses to acute or chronic stress. In part, these effects
      can involve an activation of ascending serotonergic pathways and subsequent
      changes in the expression of transcription factors that might drive
      glucocorticoid receptor expression in the hippocampus. This paper summarizes the
      evidence in favor of these pathways as well as recent studies describing
      regulatory targets within the chromatin structure of the promoter region of the
      rat hippocampal glucocorticoid receptor gene.

PMID- 15265783
TI  - Subnuclear trafficking and gene targeting by steroid receptors.
AB  - Through the use of novel imaging techniques, we have observed direct steroid
      receptor binding to a tandem array of a hormone-responsive promoter in living
      cells. We found that the glucocorticoid receptor (GR) exchanges rapidly with
      regulatory elements in the continued presence of ligand. We have also
      reconstituted a GR-dependent nucleoprotein transition with chromatin assembled on
      promoter DNA, and we discovered that GR is actively displaced from the chromatin
      template during the chromatin remodeling process. Using high-intensity UV laser
      crosslinking, we have observed highly periodic interactions of GR with promoter
      chromatin. These periodic binding events are dependent on GR-directed hSWI/SNF
      remodeling of the template and require the presence of ATP. Both the in vitro and
      in vivo results are consistent with a dynamic model ("hit-and-run") in which GR
      first binds to chromatin after ligand activation, recruits a remodeling activity,
      and is simultaneously lost from the template. We also find that receptor mobility
      in the nucleoplasm is strongly enhanced by molecular chaperones. These
      observations indicate that multiple mechanisms are involved in transient receptor
      interactions with nucleoplasmic targets.

PMID- 15265784
TI  - Differential actions of metyrapone on the fetal pituitary-adrenal axis in the
      sheep fetus in late gestation.
AB  - It is not clear if an increase in intra-adrenal cortisol is required to mediate
      the actions of adrenocorticotropic hormone (ACTH) on adrenal growth and
      steroidogenesis during the prepartum stimulation of the fetal pituitary-adrenal
      axis. We infused metyrapone, a competitive inhibitor of cortisol biosynthesis,
      into fetal sheep between 125 and 140 days of gestation (term = 147 +/- 3 days)
      and measured fetal plasma cortisol, 11-desoxycortisol, and ACTH; pituitary pro
      opiomelanocortin mRNA and adrenal expression of ACTH receptor (melanocortin type
      2 receptor), steroidogenic acute regulatory protein (StAR), 11beta-hydroxysteroid
      dehydrogenase type 2 (11betaHSD2), cytochrome P450 cholesterol side-chain
      cleavage (CYP11A1), cytochrome P450 17-hydroxylase (CYP17), 3beta-hydroxysteroid
      dehydrogenase, and cytochrome P450 21-hydroxylase mRNA; and StAR protein in the
      fetal adrenal gland. Plasma ACTH and 11-desoxycortisol concentrations were higher
      (P < 0.05), whereas plasma cortisol concentrations were not significantly
      different in metyrapone- compared with vehicle-infused fetuses. The ratio of
      plasma cortisol to ACTH concentrations was higher (P < 0.0001) between 136 and
      140 days than between 120 and 135 days of gestation in both metyrapone- and
      vehicle-infused fetuses. The combined adrenal weight and adrenocortical thickness
      were greater (P < 0.001), and cell density was lower (P < 0.01), in the zona
      fasciculata of adrenals from the metyrapone-infused group. Adrenal StAR mRNA
      expression was lower (P < 0.05), whereas the levels of mature StAR protein (30
      kDa) were higher (P < 0.05), in the metyrapone-infused fetuses. In addition,
      adrenal mRNA expression of 11betaHSD2, CYP11A1, and CYP17 were higher (P < 0.05)
      in the metyrapone-infused fetuses. Thus, metyrapone administration may represent
      a unique model that allows the investigation of dissociation of the relative
      actions of ACTH and cortisol on fetal adrenal steroidogenesis and growth during
      late gestation.

PMID- 15265785
TI  - Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a
      novel component of the BLOC-1 complex.
AB  - Hermansky-Pudlak syndrome (HPS), a disorder of organelle biogenesis, affects
      lysosomes, melanosomes, and platelet dense bodies. Seven genes cause HPS in
      humans (HPS1-HPS7) and at least 15 nonallelic mutations cause HPS in mice. Where
      their function is known, the HPS proteins participate in protein trafficking and
      vesicle docking/fusion events during organelle biogenesis. HPS-associated genes
      participate in at least 4 distinct protein complexes: the adaptor complex AP-3;
      biogenesis of lysosome-related organelles complex 1 (BLOC-1), consisting of 4 HPS
      proteins (pallidin, muted, cappuccino, HPS7/sandy); BLOC-2, consisting of
      HPS6/ruby-eye, HPS5/ruby-eye-2, and HPS3/cocoa; and BLOC-3, consisting of
      HPS1/pale ear and HPS4/light ear. Here, we report the cloning of the mouse HPS
      mutation reduced pigmentation (rp). We show that the wild-type rp gene encodes a
      novel, widely expressed 195-amino acid protein that shares 87% amino acid
      identity with its human orthologue and localizes to punctate cytoplasmic
      structures. Further, we show that phosphorylated RP is part of the BLOC-1
      complex. In mutant rp/rp mice, a premature stop codon truncates the protein after
      79 amino acids. Defects in all the 5 known components of BLOC-1, including RP,
      cause severe HPS in mice, suggesting that the subunits are nonredundant and that
      BLOC-1 plays a key role in organelle biogenesis.

PMID- 15265787
TI  - Adult Burkitt leukemia and lymphoma.
AB  - The World Health Organization Classification of Lymphoid Neoplasms identifies
      Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm
      consisting of endemic, sporadic, and immunodeficiency-associated variants. These
      subtypes share many morphologic and immunophenotypic features, but differences
      exist in their clinical and geographic presentations. All of these subtypes
      possess chromosomal rearrangements of the c-myc oncogene, the genetic hallmark of
      Burkitt lymphoma that contributes to lymphomagenesis through alterations in cell
      cycle regulation, cellular differentiation, apoptosis, cellular adhesion, and
      metabolism. Brief-duration, high-intensity chemotherapy regimens containing
      aggressive central nervous system prophylaxis have had remarkable success in the
      treatment of this disease, with complete remission rates of 75% to 90% and
      overall survivals reaching 50% to 70% in adults. Although Burkitt lymphoma cells
      are extremely chemosensitive, biologically targeted therapies should be developed
      because current treatment options are suboptimal for patients with poor
      prognostic features or in the setting of relapsed disease.

PMID- 15265786
TI  - Differential regulation of actin stress fiber assembly and proplatelet formation
      by alpha2beta1 integrin and GPVI in human megakaryocytes.
AB  - The actin cytoskeleton plays a major role in platelet function. In contrast, its
      precise role in the function of megakaryocytes (MKs) is less understood but may
      be important for a chemoattractive response and an efficient proplatelet
      formation. In the marrow microenvironment, mature MKs are in contact with the
      extracellular matrix, including fibrillar collagen type I. MKs express
      alpha2beta1 integrin and the immunoglobulin superfamily member glycoprotein VI
      (GPVI), the main receptors for collagen. Using function-blocking antibodies or
      specific ligands, we investigated in primary human MKs how alpha2beta1 integrin
      and GPVI regulate stress fiber formation, the primary actin structures needed for
      cell contraction. Stress fiber assembly requires synergistic activation of the
      MAPK/Erk1/2 pathway and the small guanosine triphosphatase Rho via its effector,
      Rho-associated coiled-coil kinase (ROCK). alpha2beta1 integrin is crucial for
      stress fiber formation, whereas GPVI triggers rapid and sustained activation of
      the Erk1/2 pathway. Strikingly, after a longer adhesion time, proplatelet
      formation was significantly inhibited by the engagement of alpha2beta1 integrin,
      not by GPVI, likely through the Rho/ROCK pathway. Thus, proplatelet formation in
      human MKs could be tightly regulated by differential interactions with their
      collagen receptors. We propose that this interaction with collagen prevents
      proplatelet formation within the marrow.

PMID- 15265788
TI  - Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70:
      results of a randomized controlled trial.
AB  - High-dose therapy is an effective standard treatment for multiple myeloma
      patients. Evidence that intermediate-dose therapy improves survival is limited.
      At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen
      is very well tolerated in older patients. In a multicenter study, 194 patients
      were randomized to receive at diagnosis either conventional chemotherapy (6
      courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2
      courses of melphalan at 100 mg/m(2) [MEL100]) with stem cell support. Response
      rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and
      25% after MEL100 (P = .0002). At 3 years, MEL100 increased event-free survival
      (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001).
      Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and
      25% after MEL100 (P = .05); at 3 years, MEL100 improved EFS from 18% to 31% (P =
      .01) and OS from 58% to 73% (P = .01). Patients aged 65 to 70 had a median OS of
      37.2 months (MP) versus 58 months (MEL100). Intermediate-dose melphalan improves
      response rate, EFS, and OS in myeloma patients, specifically in those aged 65 to
      70. It constitutes a more effective first-line regimen than standard treatment
      for elderly patients.

PMID- 15265789
TI  - Peroxisome proliferator-activated receptor-gamma and its ligands attenuate
      biologic functions of human natural killer cells.
AB  - Interferon-gamma (IFN-gamma) production and cytolytic activity are 2 major
      biologic functions of natural killer (NK) cells that are important for innate
      immunity. We demonstrate here that these functions are compromised in human NK
      cells treated with peroxisome proliferator-activated-gamma (PPAR-gamma) ligands
      via both PPAR-gamma-dependent and -independent pathways due to variation in PPAR
      gamma expression. In PPAR-gamma-null NK cells, 15-deoxy-Delta(12,14)
      prostaglandin J(2) (15d-PGJ(2)), a natural PPAR-gamma ligand, reduces IFN-gamma
      production that can be reversed by MG132 and/or chloroquine, and it inhibits
      cytolytic activity of NK cells through reduction of both conjugate formation and
      CD69 expression. In PPARgamma-positive NK cells, PPAR-gamma activation by 15d
      PGJ(2) and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and
      protein levels of IFN-gamma. Overexpression of PPAR-gamma in PPAR-gamma-null NK
      cells reduces IFN-gamma gene expression. However, PPAR-gamma expression and
      activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ(2)
      but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44
      expression is not affected. These results reveal novel pathways regulating NK
      cell biologic functions and provide a basis for the design of therapeutic agents
      that can regulate the function of NK cells within the innate immune response.

PMID- 15265791
TI  - Role of endogenous thrombin in tumor implantation, seeding, and spontaneous
      metastasis.
AB  - Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor
      growth and metastasis experiments in mice by the use of hirudin, a highly potent
      specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor
      implantation in nude or syngeneic mice, following subcutaneous injection of 2
      human and 2 murine tumors. Hirudin induced a considerable lag period in the
      appearance of tumor growth, compared with phosphate-buffered saline (PBS)
      treatment, but had no effect on established tumor nodule growth in vivo or on
      tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor
      nodule compared with no effect with PBS treatment. Greater protection was noted
      with longer duration of treatment. Tumor seeding into blood was examined with
      green fluorescent protein (GFP)-labeled tumor cells. Hirudin inhibited seeding
      into the blood as well as systemic organs which varied from complete protection
      to 15- to 32-fold in the blood and 17- to 395-fold in the lung. Hirudin inhibited
      spontaneous metastases from subcutaneously implanted tumor by reducing the number
      of tumor nodules in the lungs. Mouse survival in animals injected subcutaneously
      with highly aggressive 4T1 cells revealed 5 of 5 deaths of PBS-treated animals on
      day 40 compared with no deaths with hirudin treatment, with prolongation of
      survival with hirudin treatment of 16 days to more than 31 days. Thus, endogenous
      thrombin contributes to tumor implantation, seeding, and spontaneous metastasis.
      A potent antithrombin agent should be of clinical benefit to patients with
      cancer.

PMID- 15265790
TI  - Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix
      metalloproteinases: role of reactive oxygen species.
AB  - Lymphocytes bound at endothelial cell junctions extravasate within minutes.
      Lymphocyte-endothelial cell binding is mediated by receptors such as vascular
      cell adhesion molecule 1 (VCAM-1). VCAM-1 activates endothelial cell nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase in minutes, and this activity is
      required for VCAM-1-dependent lymphocyte migration. In this report, we examined
      mechanisms for activation of matrix metalloproteinases (MMPs) during VCAM-1
      dependent lymphocyte migration. Lymphocyte binding to VCAM-1 rapidly activated
      endothelial cell-associated MMPs. Furthermore, inhibition of MMPs on the
      endothelial cells but not on the lymphocytes blocked VCAM-1-dependent lymphocyte
      migration across endothelial cells. The activation of endothelial cell MMPs
      required VCAM-1-stimulated endothelial cell NADPH oxidase activity as determined
      by scavenging of reactive oxygen species (ROS) and by pharmacologic or antisense
      inhibition of NADPH oxidase. Exogenous addition of 1 microM H(2)O(2), the level
      of H(2)O(2) generated by VCAM-1-stimulated endothelial cells, rapidly activated
      endothelial cell-associated MMPs. In contrast, activation of lymphocyte
      associated MMPs was delayed by hours after binding to VCAM-1, and this activation
      was blocked by inhibition of endothelial cell ROS generation. There was also a
      delay in H(2)O(2)-induced decrease in lymphocyte-associated tissue inhibitors of
      metalloproteinases (TIMPs), resulting in an increase in MMP/TIMP ratio. In
      summary, this is the first report of a mechanism for ROS function in VCAM-1
      activation of endothelial cell MMPs during VCAM-1-dependent lymphocyte migration.

PMID- 15265792
TI  - Protein kinase A mediates inhibition of the thrombin-induced platelet shape
      change by nitric oxide.
AB  - The thrombin-induced platelet shape change was blocked by nitric oxide (NO), as
      revealed by scanning electron microscopy, light transmission, and resistive
      particle volume determination. The inhibitory effect of NO was accompanied by an
      increase in levels of both cyclic guanosine monophosphate (cGMP) and cyclic
      adenosine monophosphate (cAMP) and phosphorylation of the vasodilator-stimulated
      phosphoprotein (VASP). However, the inhibition of the shape change was only
      mimicked by cAMP analogs (Sp-5,6-DClcBIMPS, 8-AHA-cAMP, and 8-CPT-cAMP) and not
      by cGMP analogs (8-Br-PET-cGMP, 8-Br-cGMP, and 8-pCPT-cGMP). The effect of NO on
      the thrombin-induced shape change was prevented by the protein kinase A (PKA)
      antagonists Rp-8-Br-cAMPS and Rp-cAMPS. The protein kinase G (PKG) antagonist Rp
      8-CPT-cGMPS strongly inhibited PKG-mediated 46-kDa VASP Ser239 phosphorylation,
      but did not inhibit the thrombin-induced shape change or the PKA-mediated VASP
      Ser157 phosphorylation. Whereas an inhibitor of cyclic nucleotide
      phosphodiesterase (PDE) 3A (milrinone) mimicked the effect of NO, inhibitors of
      PDE2 (erythro-9-(2-hydroxy-3-nonyl)adenine) and PDE5 (dipyridamole) were poorly
      effective. We concluded that (1) NO was a potent and reversible inhibitor of the
      platelet shape change, (2) the shape change was reversible, (3) the inhibitory
      effect of NO was mediated through activation of PKA, (4) the onset of the NO
      effect coincided with VASP Ser157 phosphorylation, and (5) removal of NO and
      platelet shape change coincided with VASP Ser157 dephosphorylation. These
      findings are compatible with elevation of cGMP by NO in a compartment close to
      PDE3A, PKA, and VASP, leading to a local increase of cAMP able to block thrombin
      induced shape change.

PMID- 15265793
TI  - Oral anticoagulant treatment: friend or foe in cardiovascular disease?
AB  - Calcification is a common complication in cardiovascular disease and may affect
      both arteries and heart valves. Matrix gamma-carboxyglutamic acid (Gla) protein
      (MGP) is a potent inhibitor of vascular calcification, the activity of which is
      regulated by vitamin K. In animal models, vitamin K antagonists (oral
      anticoagulants [OACs]) were shown to induce arterial calcification. To
      investigate whether long-term OAC treatment may induce calcification in humans
      also, we have measured the grade of aortic valve calcification in patients with
      and without preoperative OAC treatment. OAC-treated subjects were matched with
      nontreated ones for age, sex, and disease. Calcifications in patients receiving
      preoperative OAC treatment were significantly (2-fold) larger than in nontreated
      patients. These observations suggest that OACs, which are widely used for
      antithrombotic therapy, may induce cardiovascular calcifications as an adverse
      side effect.

PMID- 15265794
TI  - Differences in the chromatin structure and cis-element organization of the human
      and mouse GATA1 loci: implications for cis-element identification.
AB  - Cis-element identification is a prerequisite to understand transcriptional
      regulation of gene loci. From analysis of a limited number of conserved gene
      loci, sequence comparison has proved a robust and efficient way to locate cis
      elements. Human and mouse GATA1 genes encode a critical hematopoietic
      transcription factor conserved in expression and function. Proper control of
      GATA1 transcription is critical in regulating myeloid lineage specification and
      maturation. Here, we compared sequence and systematically mapped position of
      DNase I hypersensitive sites, acetylation status of histone H3/H4, and in vivo
      binding of transcription factors over approximately 120 kilobases flanking the
      human GATA1 gene and the corresponding region in mice. Despite lying in
      approximately 10 megabase (Mb) conserved syntenic segment, the chromatin
      structures of the 2 homologous loci are strikingly different. The 2 previously
      unidentified hematopoietic cis-elements, one in each species, are not conserved
      in position and sequence and have enhancer activity in erythroid cells. In vivo,
      they both bind the transcription factors GATA1, SCL, LMO2, and Ldb1. More
      broadly, there are both species- and regulatory element-specific patterns of
      transcription factor binding. These findings suggest that some cis-elements
      regulating human and mouse GATA1 genes differ. More generally, mouse human
      sequence comparison may fail to identify all cis-elements.

PMID- 15265795
TI  - CD151, the first member of the tetraspanin (TM4) superfamily detected on
      erythrocytes, is essential for the correct assembly of human basement membranes
      in kidney and skin.
AB  - Tetraspanins are thought to facilitate the formation of multiprotein complexes at
      cell surfaces, but evidence illuminating the biologic importance of this role is
      sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with
      integrins alpha3beta1 and alpha6beta1 in kidney and alpha3beta1 and alpha6beta4
      in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as
      the MER2 blood group gene. We show that CD151 expresses the MER2 blood group
      antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative
      patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In
      addition to hereditary nephritis the sibs have sensorineural deafness, pretibial
      epidermolysis bullosa, and beta-thalassemia minor. The 3 patients are homozygous
      for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift
      and premature stop signal at codon 140. The resultant truncated protein would
      lack its integrin-binding domain. We conclude that CD151 is essential for the
      proper assembly of the glomerular and tubular basement membrane in kidney, has
      functional significance in the skin, is probably a component of the inner ear,
      and could play a role in erythropoiesis.

PMID- 15265796
TI  - Ability of Plasmodium falciparum to invade Southeast Asian ovalocytes varies
      between parasite lines.
AB  - Plasmodium falciparum, the causative agent of the most lethal form of human
      malaria, uses multiple ligand-receptor interactions to invade host red blood
      cells (RBCs). We studied the invasion of P falciparum into abnormal RBCs from
      humans carrying the Southeast Asian ovalocytosis (SAO) trait. One particular
      parasite line, 3D7-A, invaded these cells efficiently, whereas all other lines
      studied invaded SAO RBCs to only about 20% of the extent of normal (non-SAO)
      cells. This result is consistent with the clinical observation that SAO
      individuals can experience high-density P falciparum infections and provides an
      explanation for previous discrepant results on invasion of SAO RBCs.
      Characterization of the invasion phenotype of 3D7-A revealed that efficient
      invasion of SAO RBCs was paralleled by relatively efficient invasion of normal
      RBCs treated with either neuraminidase, trypsin, or chymotrypsin and a novel
      capacity to invade normal RBCs treated sequentially with both neuraminidase and
      trypsin. Our results suggest that only parasites able to use some particular
      invasion pathways can invade SAO RBCs efficiently in culture. A similar situation
      might occur in the field.

PMID- 15265797
TI  - Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross
      reactive and subgroup-specific CD8+ T cells.
AB  - Adenoviruses often cause lethal infections in immunocompromised individuals.
      Adoptive transfer of immune T cells offers a therapeutic option, but this
      strategy has been hindered by the paucity of information on molecular targets of
      cellular immunity and by the immunologic heterogeneity of the 51 human
      adenoviruses, which are grouped from A to F on the basis of genome size,
      composition, homology, and organization. Clonal analysis of the adenovirus
      specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals
      identified 5 novel CD8(+) T-cell epitopes, all located in conserved regions of
      the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4
      groups, while no T cells specific for a single subgroup were detected. Thus, by
      exploiting these peptide targets, it is possible to prepare a T-cell population
      capable of reacting with most adenoviruses that cause disease in
      immunocompromised patients.

PMID- 15265798
TI  - Low prevalence of circulating t(11;14)(q13;q32)-positive cells in the peripheral
      blood of healthy individuals as detected by real-time quantitative PCR.

PMID- 15265799
TI  - Human neutrophils lack granzyme A, granzyme B, and perforin.

PMID- 15265800
TI  - Granzymes A and B are not expressed in human neutrophils.

PMID- 15265801
TI  - Heparin normalizes allergen-induced nitric oxide deficiency and airway
      hyperresponsiveness.
AB  - It has been established that polycations cause airway hyperresponsiveness (AHR)
      to methacholine by inducing a deficiency of constitutive nitric oxide synthase
      (cNOS)-derived bronchodilating nitric oxide (NO). Since a deficiency of cNOS
      derived NO also contributes to allergen-induced AHR after the early asthmatic
      reaction (EAR) and since this AHR is associated with the release of polycationic
      proteins from infiltrated eosinophils in the airways, we hypothesized that
      endogenous polycations underlie or at least contribute to the allergen-induced NO
      deficiency and AHR. Using a guinea-pig model of allergic asthma, we addressed
      this hypothesis by examining the effect of the polyanion heparin, acting as a
      polycation antagonist, on the responsiveness to methacholine of isolated perfused
      tracheae from unchallenged control animals and from animals 6 h after ovalbumin
      challenge, that is, after the EAR. A 2.0-fold AHR (P<0.001) to intraluminal
      administration of methacholine was observed in airways from allergen-challenged
      animals compared to control. Incubation of these airways with 250 U ml(-1)
      heparin completely normalized the observed hyperresponsiveness (P<0.001), whereas
      the responsiveness to methacholine of airways from unchallenged control animals
      was not affected. The effect of heparin on airways from allergen-challenged
      guinea-pigs was dose-dependently (0.1 and 1.0 mM) reversed by the NOS inhibitor L
      NAME (P<0.01). These results indicate that endogenous (presumably eosinophil
      derived) polycations are involved in allergen-induced NO deficiency and AHR after
      the EAR, probably by inhibition of l-arginine transport.

PMID- 15265802
TI  - Indomethacin potentiates acetylcholine-induced vasodilation by increasing free
      radical production.
AB  - We studied the effects of indomethacin on endothelium-dependent and -independent
      vascular relaxation in rat thoracic aortic rings and its role in superoxide anion
      (O(2)(-)) production. We measured isometric force changes in response to
      acetylcholine (Ach, 1 nM-0.1 mM), sodium nitroprusside (SNP, 0.1 nM-0.1 microM; a
      nitric oxide (NO) donor) and cromakalim (1 nM-0.1 mM; a K(ATP)-channel opener) in
      aorta rings contracted with norepinephrine (NE, 0.1 microM). Indomethacin (10
      microM; 20 min) significantly increased Ach-induced vasodilation (EC(50)
      decreased from 8.99 microM to 16 nM). The free radical scavengers superoxide
      dismutase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl completely reverted
      these effects. Indomethacin did not affect SNP- or cromakalim-induced
      vasodilation. Neither acetylsalicylic acid (ASA, 5-100 microM; 15 min) nor
      ketoprofen (1-100 microM; 15 min) affected Ach, SNP and cromakalim concentration
      response curves. Incubation of the aorta with Ach (1 microM) rapidly and markedly
      increased intracellular NO fluorescence in the aorta endothelium. Indomethacin
      did not affect Ach-induced NO production. We measured intracellular O(2)(-) in
      the aorta endothelium with dihydroethidium (DHE) dye. Indomethacin significantly
      increased O(2)(-) fluorescence versus controls. Neither ASA nor ketoprofen
      affected O(2)(-) fluorescence. Nitrotyrosine staining was increased in
      indomethacin-treated aorta sections exposed to Ach, which indicates endogenous
      formation of peroxynitrite. It was low in aorta sections exposed to Ach alone or
      with ASA or ketoprofen. We cannot judge if indomethacin-induced endothelium
      dependent vasodilation damages or protects the cardiovascular system. Here, we
      show that indomethacin acts on the cardiovascular system regardless of
      cyclooxygenase inhibition.

PMID- 15265803
TI  - Evidence for gender differences in electrophysiological properties of canine
      Purkinje fibres.
AB  - Women are more prone to develop torsades de pointes, a rare life-threatening
      polymorphic ventricular tachycardia, than are men during administration of
      medicines that have the potential to block I(Kr) (rapid delayed rectifier cardiac
      K(+) current) and to prolong the QT interval. Blockade of I(Kr), hypokalaemia and
      extreme bradycardia were used to evaluate whether there are gender differences in
      cardiac repolarisation in canine Purkinje fibres (PFs). Microelectrode techniques
      were employed to measure action potential (AP) parameters in PFs from adult
      female and male dogs. Under control conditions, fibres from female animals in
      normal or low K(+) conditions exhibited significantly longer AP durations at 50%
      (APD(50)) and 90% (APD(90)) of repolarisation as compared with APDs of fibres
      from male animals. Gender-related difference to rate adaptation was also present
      in APD(90) of fibres from female animals compared to males. At a stimulation rate
      of 0.2 Hz, but not at 1.0 Hz, dofetilide elicited a significantly higher increase
      in APD(90), incidence of early afterdepolarisations, triggered and sustained
      triggered activities (TAs) in fibres from female animals compared to males in
      either normal or low K(+) conditions. The sustained TAs were reversed by raising
      the concentration of [K(+)](0) in Purkinje preparations from both male (one out
      of one) and female (12 out of 12) dogs. In conclusion, our data provide
      experimental evidence pointing to gender differences in canine AP repolarisation.
      PFs from female dogs can be used in safety pharmacology studies as a sensitive
      model for evaluating the potential proarrhythmic events in vitro of a new
      medicinal product.

PMID- 15265804
TI  - Role of different brain structures in the behavioural expression of WIN 55,212-2
      withdrawal in mice.
AB  - We have evaluated several responses induced by the cannabinoid agonist WIN 55,212
      2 related to its addictive properties, including rewarding effects and the
      development of physical dependence in mice. Moreover, we have studied the
      specific involvement of several brain regions with high density of CB1
      cannabinoid receptors, such as striatum, hippocampus, amygdala and cerebellum, in
      the behavioural expression of SR 141716A-precipitated WIN 55,212-2 withdrawal.
      The systemic administration of the CB1 receptor antagonist SR 141716A (10 mg kg(
      1), s.c.) precipitated behavioural signs of withdrawal in mice chronically
      treated with WIN 55,212-2 (1 and 2 mg kg(-1), intraperitoneal (i.p.)), revealing
      the development of physical dependence. The microinjection of SR 141716A (1.5 and
      3 micrograms) into the cerebellum induced severe manifestations of abstinence in
      mice dependent on WIN 55,212-2 (1 mg kg(-1), i.p.). Out of 10 signs evaluated,
      seven were statistically significant: wet dog shakes, body tremor, paw tremor,
      piloerection, mastication, genital licks and sniffing. When the cannabinoid
      antagonist was administered into the hippocampus and the amygdala, a moderate but
      significant withdrawal syndrome was also observed. However, no signs of
      abstinence were induced when SR 141716A was microinjected into the striatum. WIN
      55,212-2 produced rewarding effects in the place-conditioning paradigm in mice
      pre-exposed to a priming injection of the drug. These results show a reliable
      behavioural model to reveal rewarding effects and physical dependence induced by
      the repeated administration of WIN 55,212-2 in mice. The cerebellum and to a
      lesser extent the hippocampus and the amygdala participate in the behavioural
      expression of cannabinoid withdrawal.

PMID- 15265805
TI  - Matrix metalloproteinase expression and activity in human airway smooth muscle
      cells.
AB  - Airway remodelling is a feature of chronic asthma comprising smooth muscle
      hypertrophy and deposition of extracellular matrix (ECM) proteins. Matrix
      metalloproteinases (MMPs) breakdown ECM, are involved in tissue remodelling and
      have been implicated in airway remodelling. Although mesenchymal cells are an
      important source of MMPs, little data are available on airway smooth muscle (ASM)
      derived MMPs. We therefore investigated MMP and tissue inhibitor of
      metalloproteinase (TIMP) production and activity in human ASM cells. MMPs and
      TIMPs were examined using quantitative real-time RT-PCR, Western blotting,
      zymography and a quench fluorescence (QF) assay of total MMP activity. The most
      abundant MMPs were pro-MMP-2, pro- MMP-3, active MMP-3 and MT1-MMP. TIMP-1 and
      TIMP-2 expression was low in cell lysates but high in conditioned medium. High
      TIMP secretion was confirmed by the ability of ASM-conditioned medium to inhibit
      recombinant MMP-2 in a QF assay. Thrombin increased MMP activity by activation of
      pro-MMP-2 independent of the conventional smooth muscle thrombin receptors PAR 1
      and 4. In conclusion, ASM cells express pro-MMP-2, pro and active MMP-3, MMP-9
      and MT1-MMP. Unstimulated cells secrete excess TIMP 1 and 2, preventing
      proteolytic activity. MMP-2 can be activated by thrombin which may contribute to
      airway remodelling.

PMID- 15265806
TI  - Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP-
      and thrombin-induced human platelet activation.
AB  - The objective of this study was to investigate if there is a synergistic effect
      of a combination of P2Y(12) and P2Y(1) inhibition and P2Y(12) and thrombin
      inhibition, on ADP- and thrombin-induced platelet activation, respectively. The
      rationale being that these combinations will cause a concurrent inhibition of
      both G alpha(q) and Galpha (i) signalling. Blood from healthy volunteers was
      preincubated with AR-C69931MX, a reversible P2Y(12) antagonist; MRS2179, a
      reversible P2Y(1) antagonist; or melagatran, a direct reversible thrombin
      inhibitor; alone or in various combinations prior to activation with ADP or
      thrombin. Platelet function in whole blood was assessed by flow cytometry using
      the antibody PAC-1 to estimate the expression of active alpha (IIb)beta(3) (the
      fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing
      the concentrations in the different combinations with those of corresponding
      equipotent concentrations of each single inhibitor alone. The equipotent single
      concentrations were experimentally obtained from concentration response curves
      performed in parallel. A synergistic effect regarding inhibition of ADP-induced
      platelet activation (10 microM) was obtained with different combinations of AR
      C69931MX and MRS2179. Inhibition of thrombin-induced platelet activation (2 nM)
      with combinations of AR-C69931MX and the thrombin inhibitor melagatran did also
      result in a strong synergistic effect. To our knowledge, this is the first time
      that data supporting a synergistic effect has been published for the inhibitor
      combinations described. Whether this synergistic effect in vitro also results in
      an improved antithrombotic effect in vivo with or without an increased risk of
      bleeding remains to be studied in well-conducted clinical studies.

PMID- 15265807
TI  - Triazine dyes are agonists of the NAADP receptor.
AB  - NAADP has been shown to be a potent calcium-releasing second messenger in a wide
      variety of cell types to date. However, research has been hampered by a lack of
      pharmacological agents, with which to investigate NAADP-induced calcium release,
      and by the molecular identity of its cellular target protein being unknown. In
      the present paper, the sea urchin egg model was used to investigate whether
      triazine dyes, which can act as nucleotide mimetics, can bind to the NAADP
      receptor, induce Ca(2+) release and be used for affinity chromatography of the
      receptor. Indeed, all the triazine dyes tested (Reactive Red 120 (RR120),
      Reactive Green 19 (RG19), Reactive Green 5 (RG5), Cibacron Blue 3GA and Reactive
      Yellow 86) displayed micromolar affinities, except for Reactive Orange 14.
      Furthermore, unlike NAADP, RR120, RG19 and RG5 did not bind in an irreversible
      manner. The compound that displayed the highest affinity, RR120, was tested in a
      (45)Ca(2+) efflux assay. This compound released Ca(2+) via the NAADP receptor, as
      shown by the ability of subthreshold NAADP concentrations to inhibit this
      release. Furthermore, heparin and ruthenium red were unable to block RR120
      induced Ca(2+) release. We have also shown that RG5 and RG19, immobilised on
      resins, retain the ability to bind to the receptor, and that this interaction can
      be disrupted by high salt concentrations. As a proof of principle, we have shown
      that this can be used to partially purify the NAADP receptor by at least 75-fold.
      In conclusion, triazine dyes interact with the NAADP receptor, and this could be
      exploited in future to create a new generation of pharmacological tools to
      investigate this messenger and, in combination with other techniques, to purify
      the receptor.

PMID- 15265808
TI  - Increased wakefulness, motor activity and decreased theta activity after blockade
      of the 5-HT2B receptor by the subtype-selective antagonist SB-215505.
AB  - Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave
      sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT(2A) and 5
      HT(2C) receptors may be involved in these effects, but the role of the 5-HT(2B)
      receptor is still unclear. To investigate the role of the 5-HT(2B) receptor in
      regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505
      (0.1, 0.3 and 1.0 mg kg(-1) i.p.) was administered to Sprague-Dawley rats at
      light onset (beginning of passive phase). EEG, EMG and motor activity were
      recorded during the subsequent 8 h. SB-215505 dose-dependently increased
      wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical
      sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly
      increased motor activity was found. Spectral analysis of the EEG in W showed a
      dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum
      effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low
      frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505
      treatment. In PS, the drug dose-dependently decreased EEG power solely in the
      theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). The well
      known SWS-2 enhancing effect of 5-HT(2) receptor antagonists is mediated by 5
      HT(2A) and/or 5-HT(2C) receptors. In contrast, blockade of 5-HT(2B) receptors
      increases motor activity and W along with decreased theta activity during W and
      PS. Activation of 5-HT(2B) receptors may contribute to initiation of sleep and to
      theta generation during W and PS under physiological conditions.

PMID- 15265809
TI  - The NAADP receptor: commentary on Billington et al.
AB  - NAADP is a recently described calcium-mobilizing messenger. First discovered as a
      potent calcium-releasing molecule in sea urchin eggs, its actions have now been
      reported in several mammalian cell types. In the sea urchin egg, NAADP-sensitive
      calcium release channels appear distinct from inositol trisphosphate or ryanodine
      receptors, and are mainly localized to acidic compartments. In this study,
      Billington et al. extend the pharmacology of the putative NAADP receptor
      utilizing molecules unrelated to NAADP itself. This work may provide an important
      step in developing selective NAADP receptor modulators that will help define the
      role of NAADP in cell signalling.

PMID- 15265810
TI  - Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13
      generation from human basophils.
AB  - The aim of the present study was to determine whether inhibition of cyclic
      nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the
      cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was
      addressed by evaluating the effects of both nonselective and selective inhibitors
      of PDEs on the generation of cytokines from basophils. The nonselective PDE
      inhibitors, isobutyl-methylxanthine (IBMX) and theophylline, attenuated the IgE
      mediated generation of IL-4 and IL-13 and, also, the release of histamine from
      basophils. The effects of the isoform-selective inhibitors, 8-methoxymethyl-IBMX
      (PDE 1 inhibitor), siguazodan (PDE3 inhibitor), rolipram (PDE4 inhibitor),
      denbufylline (PDE4 inhibitor), Org 30029 (mixed PDE3 and 4 inhibitor) and
      zaprinast (PDE5 inhibitor), were studied. Of these selective compounds, only
      rolipram, denbufylline and Org 30029 inhibited the IgE-dependent generation of IL
      4, IL-13 and histamine from basophils to a statistically significant (P<0.05)
      degree. The effects of isoform-selective inhibitors on basophils activated by IL
      3 were evaluated. The IL-3-induced generation of IL-4, IL-13 and histamine was
      inhibited to a statistically significant (P<0.05) extent, only by compounds that
      act as inhibitors of PDE4. These data suggest that inhibition of PDE4 can
      regulate the generation of cytokines from human basophils.

PMID- 15265812
TI  - Cellular actions of somatostatin on rat periaqueductal grey neurons in vitro.
AB  - Functional studies indicate that the midbrain periaqueductal grey (PAG) is
      involved in the analgesic actions of somatostatin; however, the cellular actions
      of somatostatin in this brain region are unknown. In the present study, whole
      cell patch clamp recordings were made from rat PAG neurons in vitro. In 93% of
      acutely isolated neurons, somatostatin inhibited Ca(2+)-channel currents. This
      effect was mimicked by the sst-2 selective agonist BIM-23027, but not by the sst
      1 and sst-5 selective agonists CH-275 and L-362855. In brain slices, 81% of
      neurons responded to somatostatin (300 nm) with an increase in K(+) conductance
      that reversed polarity at -114 mV. A greater proportion of somatostatin-sensitive
      neurons (93%) than somatostatin-insensitive neurons (53%) responded to the opioid
      agonist met-enkephalin (10 microm). Somatostatin also reduced the amplitude of
      evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs). The actions of
      somatostatin in brain slices were mimicked by BIM-23027, but not by CH-275.
      Somatostatin had a variable effect on the rate of spontaneous miniature IPSCs in
      normal external potassium solutions. In high external potassium solutions,
      somatostatin reduced the rate of miniature IPSCs in all neurons, and this
      inhibition was abolished by addition of Cd(2+) (30 microm). Somatostatin had no
      effect on the amplitude of miniature IPSCs. These results indicate that
      somatostatin acts via sst-2 receptors to directly inhibit a subpopulation of PAG
      neurons by activating a potassium conductance and inhibits GABA release within
      PAG via a presynaptic Ca(2+)-dependent mechanism. Thus, like opioids,
      somatostatin has the potential to exert pre- and postsynaptic disinhibitory
      effects within the PAG.

PMID- 15265811
TI  - Dopamine D3 receptor-mediated inhibition of Na+/H+ exchanger activity in
      normotensive and spontaneously hypertensive rat proximal tubular epithelial
      cells.
AB  - This study evaluated the response of the Na(+)/H(+) exchanger (NHE) to dopamine
      D(1)- and D(2)-like receptor stimulation in immortalized renal proximal tubular
      epithelial cells and freshly isolated renal proximal tubules from the
      spontaneously hypertensive rat (SHR) and their normotensive controls (Wistar
      Kyoto rats; WKY). Stimulation of D(1)-like receptors with SKF 38393 attenuated
      NHE activity in WKY cells (IC(50)=151 nM), but not in SHR cells. Stimulation of
      D(2)-like receptors with quinerolane (IC(50)=120 nM) attenuated NHE activity in
      SHR cells, but not in WKY cells. Forskolin was equipotent in SHR and WKY cells in
      inhibiting NHE activity. The effect of SKF 38393 was abolished by overnight
      treatment of WKY cells with cholera toxin (CTX, 500 ng ml(-1)), but not with
      pertussis toxin (PTX, 100 ng ml(-1)). The effect of quinerolane (1 microm) was
      abolished by overnight treatment of SHR cells with PTX, but not with CTX. The
      D(3) receptor agonist 7-OH-DPAT (IC(50)=0.8 microM) attenuated NHE activity in
      SHR cells only. This effect was abolished by S-sulpiride and by overnight
      treatment with PTX. The D(4) receptor agonist RBI 257 did not affect NHE
      activity. The 7-OH-DPAT inhibited NHE activity in freshly isolated renal proximal
      tubules from 4- and 12-week-old SHR and 12-week-old WKY, but not in freshly
      isolated renal proximal tubules from 4-week-old WKY. It is concluded that D(3)
      receptors coupled to a G(i/o) protein play a role in the handling of tubular
      Na(+), namely through inhibition of the NHE activity, this being of particular
      relevance in the SHR, which fail to respond to D(1)-like dopamine receptor
      stimulation.

PMID- 15265813
TI  - Is trust an under-researched component of healthcare organisation?

PMID- 15265814
TI  - General practitioners' perceptions of sharing workload in group practices:
      qualitative study.
AB  - OBJECTIVE: To explore general practitioners' beliefs and experiences of
      distribution of workload and teamwork between doctors in general practice.
      DESIGN: Qualitative semistructured interview study. SETTING: South London.
      PARTICIPANTS: 18 general practitioners from 11 practices. MAIN OUTCOME MEASURES:
      Perceptions and experiences of distribution of workload and teamwork between
      doctors. RESULTS: Equitable distribution of workload was a common concern among
      general practitioners in group practices. Several ways of addressing the problem
      were identified, including relying on trust, creating systems of working based on
      explicit rules such as points' systems, and improving communication. Improvement
      of communication was hampered by the taboo nature of the problem. CONCLUSION:
      Resentment about perceived inequalities in workload places a further burden on
      general practices. The issue of working together warrants further support.

PMID- 15265815
TI  - Impact of counselling on careseeking behaviour in families with sick children:
      cluster randomised trial in rural India.
AB  - OBJECTIVE: To assess whether training doctors in counselling improves careseeking
      behaviour in families with sick children. DESIGN: Pair matched, community
      randomised trial conducted in 12 primary health centres (six pairs). Doctors in
      intervention centres were trained in counselling, communication, and clinical
      skills, using the integrated management of childhood illness approach. SETTING:
      Rural district in Rajasthan, India. PARTICIPANTS: Children aged under 5 years
      presenting for curative care and their mothers were recruited and visited monthly
      at home for six months. A total of 2460 children were recruited (1248
      intervention, 1212 control). MAIN OUTCOME MEASURES: Careseeking behaviour of
      mothers for sick children; mothers' knowledge and perceptions of seeking care;
      counselling performance of doctors. RESULTS: For episodes of illness with at
      least one reported danger sign, 15% of intervention group mothers and 10% of
      control group mothers reported having sought care from an appropriate provider
      promptly; this difference was not statistically significant (relative risk
      reduction 5%, 95% confidence interval -0.4% to 11%; P = 0.07). One month after
      training, intervention site doctors counselled more effectively than control
      group doctors, but at six months their performance had declined. A greater
      proportion of mothers in the intervention group than in the control group
      recalled having had at least one danger sign explained (45% v 8%; P = 0.02).
      CONCLUSIONS: Mothers' appreciation of the need to seek prompt and appropriate
      care for severe episodes of childhood illness increased, but their careseeking
      behaviour did not improve significantly.

PMID- 15265816
TI  - Early effect of pravastatin on serum soluble CD40L, matrix metalloproteinase-9,
      and C-reactive protein in patients with acute myocardial infarction.

PMID- 15265817
TI  - Ischemia-modified albumin concentrations in patients with peripheral vascular
      disease and exercise-induced skeletal muscle ischemia.
AB  - BACKGROUND: Ischemia-modified albumin (IMA) is a new marker of myocardial
      ischemia, there is concern that IMA concentrations may be affected by ischemia
      occurring in tissues other than the myocardium. METHODS: We assessed 23
      consecutive patients (15 males; mean age, 67 years) with typical leg claudication
      and documented peripheral vascular disease (PVD). All patients underwent both
      treadmill-exercise stress testing to induce leg ischemia and dobutamine stress
      echocardiography 1 week apart for the assessment of myocardial ischemia. Blood
      samples for IMA measurements were obtained at baseline, immediately after peak
      exercise/stress, and 1 h after exercise/stress. Statistical analysis was
      performed with the ANOVA repeated-measures test. RESULTS: Compared with baseline,
      mean (SD) IMA was significantly lower after the induction of skeletal muscle
      ischemia and returned to baseline values at 1 h: baseline, 74.6 (15.6)
      kilounits/L; peak stress, 69.5 (14.0) kilounits/L (P <0.0001 vs baseline); 1 h
      after stress, 75.9 (15.7) kilounits/L (P <0.0001 vs peak stress; P = 0.3 vs
      baseline). Baseline, peak stress, and 1-h poststress IMA concentrations were
      inversely correlated with the ankle-brachial index after exercise (r = -0.4; P
      <0.05). None of the patients showed regional wall motion abnormalities during
      dobutamine stress echocardiography, and IMA concentrations remained unchanged
      from baseline. There were no differences in baseline [74.6 (15.6) vs 72.7 (11.5)
      kilounits/L; P = 0.6], peak stress, or poststress IMA concentrations when
      exercise testing and dobutamine stress echocardiography values were compared.
      CONCLUSIONS: The relationship between disease severity (of a noncardiac origin)
      and baseline IMA values is an important and novel finding. IMA is significantly
      lower immediately after exercise-induced leg ischemia in patients with PVD and is
      related to disease severity. IMA concentrations can therefore be affected by the
      development of skeletal muscle ischemia, and this may have implications regarding
      the ability of IMA to detect myocardial ischemia in PVD patients.

PMID- 15265818
TI  - Endocrine regulation of energy metabolism: review of pathobiochemical and
      clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin.
AB  - BACKGROUND: Recent studies point to the adipose tissue as a highly active
      endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and
      resistin are considered to take part in the regulation of energy metabolism.
      APPROACH: This review summarizes recent knowledge on leptin and its receptor and
      on ghrelin, adiponectin, and resistin, and emphasizes their roles in
      pathobiochemistry and clinical chemistry. CONTENT: Leptin, adiponectin, and
      resistin are produced by the adipose tissue. The protein leptin, a satiety
      hormone, regulates appetite and energy balance of the body. Adiponectin could
      suppress the development of atherosclerosis and liver fibrosis and might play a
      role as an antiinflammatory hormone. Increased resistin concentrations might
      cause insulin resistance and thus could link obesity with type II diabetes.
      Ghrelin is produced in the stomach. In addition to its role in long-term
      regulation of energy metabolism, it is involved in the short-term regulation of
      feeding. These hormones have important roles in energy homeostasis, glucose and
      lipid metabolism, reproduction, cardiovascular function, and immunity. They
      directly influence other organ systems, including the brain, liver, and skeletal
      muscle, and are significantly regulated by nutritional status. This newly
      discovered secretory function has extended the biological relevance of adipose
      tissue, which is no longer considered as only an energy storage site. SUMMARY:
      The functional roles, structures, synthesis, analytical aspects, and clinical
      significance of leptin, ghrelin, adiponectin, and resistin are summarized.

PMID- 15265819
TI  - Molecular heterogeneity has a major impact on the measurement of circulating N
      terminal fragments of A- and B-type natriuretic peptides.
AB  - BACKGROUND: The N-terminal fragments of A- and B-type natriuretic peptides (NT
      proANP and NT-proBNP) are powerful markers of cardiac function. The current
      assays require refinement with regard to standardization with native calibrators
      and the ability to detect the actual circulating forms. METHODS: The following
      peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1
      108, and Tyr0-proBNP77-108. Fifteen peptides of 13-22 amino acids, spanning the
      sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide
      synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up,
      each with a different epitope specificity. The assays were applied for the
      measurement of NT-proANP and NT-proBNP in healthy individuals and in patients
      with acute myocardial infarction. The circulating molecular forms were analyzed
      by gel-filtration and reversed-phase HPLC. RESULTS: According to the HPLC
      analyses, circulating NT-proANP consists mainly of the full-length peptide, with
      some degradation at both ends. In contrast, circulating NT-proBNP is very
      heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size
      than NT-proBNP1-76, with truncation at both termini. The smallest fragments can
      be detected by assays directed at the central part of NT-proBNP only; assays
      directed at the ends gave 30-40% lower values. Despite the difference, the
      various assays correlated reasonably well with each other (r2 = 0.77-0.85). In
      patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations
      were 1.8-2.3 and 4.2-4.5 times higher than in healthy individuals. The
      development of heart failure further increased the concentrations. CONCLUSIONS:
      Molecular heterogeneity of the circulating forms causes a serious risk of
      preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP.
      The development of a sandwich assay for NT-proBNP would be especially
      challenging. The most robust and reliable assays use antibodies directed at the
      central portions of NT-proANP or NT-proBNP.

PMID- 15265820
TI  - One-step analysis of ten functional haplotype combinations of the basic RET
      promoter with a LightCycler assay.

PMID- 15265821
TI  - Biochemistry of pro-B-type natriuretic peptide-derived peptides: the endocrine
      heart revisited.
AB  - BACKGROUND: Since the discovery of cardiac hormones almost 25 years ago, a vast
      amount of clinical research has identified the cardiac natriuretic peptides and
      their precursors as markers of heart failure. It even seems likely that the pro-B
      type natriuretic peptide (proBNP)-derived peptides in plasma may become the most
      frequently measured peptides in the daily diagnosis and control of therapy. In
      contrast, the biochemistry of the peptides has received less attention. METHODS:
      Published data available on the National Library of Medicine (NLM) were used as
      the basis for the review. OUTCOME: This review shows that the present
      understanding of the biochemistry of peptides is far from complete. In
      particular, cellular synthesis, including posttranslational precursor maturation,
      is poorly understood. Moreover, elimination of the precursor fragments is
      unknown. Elucidation of the molecular heterogeneity of proBNP products will
      therefore contribute to the understanding of the endocrine heart and may also
      have important diagnostic consequences. Above all, the different proBNP-derived
      peptides may not always be equal markers of the same pathophysiologic processes.
      A different metabolism and peripheral elimination may also impose new and peptide
      specific limitations for diagnostic use. CONCLUSIONS: It is necessary to focus
      more on the biology of the proBNP-derived peptides. In turn, new insight into the
      biochemistry could pave the way for more sensitive and disease-specific assays in
      the clinical setting.

PMID- 15265822
TI  - Parathyroid hormone-related protein: an essential physiological regulator of
      adult bone mass.

PMID- 15265823
TI  - Beta-cell lipotoxicity: burning fat into heat?

PMID- 15265824
TI  - Interleukin-6 access to the axis.

PMID- 15265825
TI  - Outside-in and inside-out signaling: the new concept that selectivity of ligand
      binding at the gonadotropin-releasing hormone receptor is modulated by the
      intracellular environment.

PMID- 15265826
TI  - Evidence for abnormal translational regulation of renal 25-hydroxyvitamin D
      1alpha-hydroxylase activity in the hyp-mouse.
AB  - Hyp-mice exhibit abnormal regulation of 25-hydroxyvitamin D [25(OH)D]-1alpha
      hydroxylase activity. Previous observations suggest such aberrant modulation is
      posttranscriptional. To investigate this possibility further, we examined whether
      hyp-mice manifest abnormal translation of 25(OH)D-1alpha-hydroxylase mRNA. We
      compared phosphate, parathyroid, and calcitonin effects on renal 25(OH)D-1alpha
      hydroxylase protein as well as mRNA and enzyme activity in normal and hyp-mice.
      We assayed protein by Western blots, mRNA by real-time RT-PCR, and enzyme
      activity by measuring 1,25-dihydroxyvitamin D production. Although phosphate
      depleted mice exhibited enhanced enzyme function, with significantly increased
      mRNA and protein expression, hyp-mice comparably increased mRNA but failed to
      augment enzyme activity, concordant with an inability to increase protein
      expression. PTH stimulation increased mRNA and protein expression as well as
      enzyme activity in normal mice but in hyp-mice, despite effecting mRNA
      enhancement, did not increment enzyme function or protein. The inability of
      hypophosphatemia and PTH to increase 25(OH)D-1alpha-hydroxylase activity and
      protein expression in hyp-mice was not universal because calcitonin stimulation
      was normal, suggesting proximal convoluted tubule localization of the defect.
      These data, in accord with absent undue enhancement of protein expression in hyp
      mice treated with protease inhibitors, establish that abberrant regulation of
      vitamin D metabolism results from abnormal translational activity.

PMID- 15265831
TI  - Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes
      and Haemophilus influenzae collected from patients across the USA, in 2001-2002,
      as part of the PROTEKT US study.
AB  - BACKGROUND: The PROTEKT US (Prospective Resistant Organism Tracking and
      Epidemiology for the Ketolide Telithromycin in the United States) surveillance
      programme was started in 2000, to chart the emergence and spread of antimicrobial
      resistance among isolates of Streptococcus pneumoniae, Streptococcus pyogenes and
      Haemophilus influenzae from across the USA. METHODS: In 2001-2002 (Year 2 of
      PROTEKT US) 242 centres from 46 states and the territory of Puerto Rico submitted
      a total of 10 012 S. pneumoniae, 4508 S. pyogenes and 3296 H. influenzae isolates
      from community-acquired respiratory tract infections (CARTIs). Susceptibility
      testing was performed and interpreted using NCCLS methodology and criteria.
      RESULTS: Overall, 35.4% of S. pneumoniae were non-susceptible to penicillin
      (14.2% intermediate, MIC 0.12-1 mg/L; 21.2% resistant, MIC > or =2 mg/L) and
      27.9% were resistant to erythromycin (MIC > or =1 mg/L) (0.2% intermediate, MIC
      0.5 mg/L). A total of 105 (1.0%) isolates were resistant to levofloxacin (MIC >
      or =8 mg/L). More than 99.2% of isolates were susceptible to telithromycin (MIC <
      or =1 mg/L) irrespective of penicillin and/or erythromycin resistance. All S.
      pyogenes isolates were susceptible to penicillin (MIC < or =0.12 mg/L) and 5.7%
      were resistant to erythromycin (MIC > or =1 mg/L) (0.3% intermediate, MIC 0.5
      mg/L). The MIC90 of telithromycin for S. pyogenes was 0.03 mg/L. A total of 27.5%
      of H. influenzae isolates were beta-lactamase producers. Overall, 27.8% were
      resistant (MIC > or =4 mg/L) and 1.1% were intermediate to ampicillin (MIC 2
      mg/L). A total of 96.3% of H. influenzae isolates were susceptible to
      telithromycin (MIC < or =4 mg/L). CONCLUSIONS: Antimicrobial resistance continues
      to be a problem in the USA. The ketolide telithromycin continues to show high
      activity against common CARTI pathogens, including those resistant to beta
      lactams and macrolides.

PMID- 15265832
TI  - Distribution across the USA of macrolide resistance and macrolide resistance
      mechanisms among Streptococcus pneumoniae isolates collected from patients with
      respiratory tract infections: PROTEKT US 2001-2002.
AB  - BACKGROUND: Resistance to the macrolides has increased rapidly among isolates of
      Streptococcus pneumoniae from community-acquired respiratory tract infections
      (CARTIs). METHODS: A total of 10 012 S. pneumoniae isolates were submitted from
      46 US states and the territory of Puerto Rico in the PROTEKT US Year 2 (2001
      2002) surveillance study. Antimicrobial susceptibilities were determined
      according to NCCLS guidelines and genes encoding common macrolide resistance
      mechanisms were sought by PCR. RESULTS: Overall, 27.9% (n=2793) of S. pneumoniae
      isolates were macrolide (erythromycin) resistant; the highest prevalence was
      recorded in Louisiana (48.2%). Of the 2738 genotyped macrolide-resistant S.
      pneumoniae, 68.7% possessed mef(A) (state range: Delaware 40.0%-Georgia 84.8%),
      16.8% of isolates harboured erm(B) (Georgia 6.1%-Idaho and Rhode Island both
      36.4%) and 12.2% possessed erm(B) + mef(A) (Arkansas and Rhode Island 0%-South
      Dakota 32.9%). Five isolates possessed an erm(A) subclass erm(TR) gene (from
      California, Illinois, Missouri, Pennsylvania and Virginia), while the mechanisms
      for 56 isolates were not definable by the methods used in this study.
      Susceptibility to telithromycin was high, irrespective of macrolide resistance
      mechanism, with > or =96.4% of the macrolide-resistant isolates susceptible.
      CONCLUSIONS: The prevalence of macrolide resistance and the resistance mechanisms
      among S. pneumoniae isolates are highly variable among the US states.
      Telithromycin may represent an effective treatment option for CARTIs caused by
      macrolide-resistant pneumococci.

PMID- 15265833
TI  - Antibacterial susceptibility among Streptococcus pneumoniae isolated from
      paediatric and adult patients as part of the PROTEKT US study in 2001-2002.
AB  - BACKGROUND: One of the main factors commonly associated with antibacterial
      resistance among Streptococcus pneumoniae is the age of the patient. The highest
      rates of resistance have often been reported among isolates from young children.
      METHODS: Data from the PROTEKT US (Prospective Resistant Organism Tracking and
      Epidemiology for the Ketolide Telithromycin in the United States) surveillance
      study were examined to determine the level of antibacterial resistance among S.
      pneumoniae isolates collected in 2001-2002 from different patient age groups in
      the USA. RESULTS: A total of 10 012 clinical isolates of S. pneumoniae were
      submitted by 242 centres across the USA and categorized into four patient age
      groups: infants (0-2 years, n = 1556), children (3-14 years, n=1125), adults (15
      64 years, n=4058) and elderly adults (> or =65 years, n = 3067) (age unknown
      n=206). With the exception of the fluoroquinolones and linezolid, rates of
      antibacterial resistance were highest among infants and decreased with increasing
      patient age. Resistance to penicillin ranged from 33.6% among infants to 17.5%
      among elderly adults, and erythromycin resistance ranged from 41.1% among infants
      to 24.0% among adults. In contrast, levofloxacin resistance increased with
      patient age (from 0.1% to 1.6%). The highest rates of susceptibility were noted
      for telithromycin and linezolid (> or =99.6% and > or =99.8% susceptible
      isolates, respectively). CONCLUSIONS: The PROTEKT US study data confirmed that
      the highest antibacterial resistance rates were associated with isolates
      collected from young children (0-2 years). Telithromycin may offer a reliable
      alternative to first-line drugs in the empirical treatment of community-acquired
      respiratory tract infections.

PMID- 15265834
TI  - Are OTC statins ready for prime time?

PMID- 15265835
TI  - Access to clean water and sanitation pose 21st-century challenge for millions.

PMID- 15265836
TI  - Genes harbor clues to addiction, recovery.

PMID- 15265837
TI  - FDA warns against breast milk drug.

PMID- 15265844
TI  - Inhaled nitric oxide in acute lung injury.

PMID- 15265845
TI  - HER-2 and fluorescent in situ hybridization to evaluate breast cancer.

PMID- 15265846
TI  - Frequency of ejaculation and risk of prostate cancer.

PMID- 15265847
TI  - Efficacy and safety of statin therapy in children with familial
      hypercholesterolemia: a randomized controlled trial.
AB  - CONTEXT: Children with familial hypercholesterolemia have endothelial dysfunction
      and increased carotid intima-media thickness (IMT), which herald the premature
      atherosclerotic disease they develop later in life. Although intervention therapy
      in the causal pathway of this disorder has been available for more than a decade,
      the long-term efficacy and safety of cholesterol-lowering medication have not
      been evaluated in children. OBJECTIVE: To determine the 2-year efficacy and
      safety of pravastatin therapy in children with familial hypercholesterolemia.
      DESIGN: Randomized, double-blind, placebo-controlled trial that recruited
      children between December 7, 1997, and October 4, 1999, and followed them up for
      2 years. SETTING AND PARTICIPANTS: Two hundred fourteen children with familial
      hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical
      referral center in the Netherlands. INTERVENTION: After initiation of a fat
      restricted diet and encouragement of regular physical activity, children were
      randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106),
      or a placebo tablet (n = 108). MAIN OUTCOME MEASURES: The primary efficacy
      outcome was the change from baseline in mean carotid IMT compared between the 2
      groups over 2 years; the principal safety outcomes were growth, maturation, and
      hormone level measurements over 2 years as well as changes in muscle and liver
      enzyme levels. RESULTS: Compared with baseline, carotid IMT showed a trend toward
      regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a
      trend toward progression was observed in the placebo group (mean [SD], +0.005
      [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups
      (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly
      reduced mean low-density lipoprotein cholesterol levels compared with placebo (
      24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth,
      muscle or liver enzymes, endocrine function parameters, Tanner staging scores,
      onset of menses, or testicular volume between the 2 groups. CONCLUSION: Two years
      of pravastatin therapy induced a significant regression of carotid
      atherosclerosis in children with familial hypercholesterolemia, with no adverse
      effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

PMID- 15265848
TI  - Antidepressants and the risk of suicidal behaviors.
AB  - CONTEXT: The relation between use of antidepressants, especially selective
      serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has
      received considerable public attention recently. The use of such drugs among
      teenagers has been of particular concern. OBJECTIVE: To estimate the relative
      risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1
      of 3 antidepressant drugs compared with patients starting treatment with
      dothiepin. DESIGN AND SETTING: Matched case-control study of patients treated in
      UK general practices using the UK General Practice Research Database for 1993
      1999. PARTICIPANTS: The base population included 159,810 users of the 4
      antidepressant drugs. Participants could have used only 1 of these
      antidepressants and had to have received at least 1 prescription for the study
      antidepressant within 90 days before their index date (the date of suicidal
      behavior or ideation for cases and the same date for matched controls). MAIN
      OUTCOME MEASURES: Frequency of first-time exposure to amitriptyline, fluoxetine,
      paroxetine, and dothiepin of patients with a recorded diagnosis of first-time
      nonfatal suicidal behavior or suicide compared with comparable patients who did
      not exhibit suicidal behavior. RESULTS: After controlling for age, sex, calendar
      time, and time from first antidepressant prescription to the onset of suicidal
      behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in
      555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13)
      for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI,
      0.97-1.70) for paroxetine compared with those using dothiepin. The RR for
      suicidal behavior among patients first prescribed an antidepressant within 1 to 9
      days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients
      who were first prescribed an antidepressant 90 days or more before their index
      date. Time since first antidepressant prescription was not, however, a confounder
      of the relation between specific antidepressants and suicidal behavior since its
      relation to suicidal behavior was not materially different among users of the 4
      study drugs. Similarly for fatal suicide, the RR among patients who were first
      prescribed an antidepressant within 1 to 9 days before their index date was 38.0
      (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant
      90 days or more before their index date. There were no significant associations
      between the use of a particular study antidepressant and the risk of suicide.
      CONCLUSIONS: The risk of suicidal behavior after starting antidepressant
      treatment is similar among users of amitriptyline, fluoxetine, and paroxetine
      compared with the risk among users of dothiepin. The risk of suicidal behavior is
      increased in the first month after starting antidepressants, especially during
      the first 1 to 9 days. A possible small increase in risk (bordering statistical
      significance) among those starting the newest antidepressant, paroxetine, is of a
      magnitude that could readily be due to uncontrolled confounding by severity of
      depression. Based on limited information, we also conclude that there is no
      substantial difference in effect of the 4 drugs on people aged 10 to 19 years.

PMID- 15265849
TI  - Trends in heart failure incidence and survival in a community-based population.
AB  - CONTEXT: The epidemic of heart failure has yet to be fully investigated, and data
      on incidence, survival, and sex-specific temporal trends in community-based
      populations are limited. OBJECTIVE: To test the hypothesis that the incidence of
      heart failure has declined and survival after heart failure diagnosis has
      improved over time but that secular trends have diverged by sex. DESIGN, SETTING,
      AND PARTICIPANTS: Population-based cohort study using the resources of the
      Rochester Epidemiology Project conducted in Olmsted County, Minnesota. Patients
      were 4537 Olmsted County residents (57% women; mean [SD] age, 74 [14] years) with
      a diagnosis of heart failure between 1979 and 2000. Framingham criteria and
      clinical criteria were used to validate the diagnosis MAIN OUTCOME MEASURES:
      Incidence of heart failure and survival after heart failure diagnosis. RESULTS:
      The incidence of heart failure was higher among men (378/100 000 persons; 95%
      confidence interval [CI], 361-395 for men; 289/100 000 persons; 95% CI, 277-300
      for women) and did not change over time among men or women. After a mean follow
      up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred, including 1930 among
      women and 1417 among men. Survival after heart failure diagnosis was worse among
      men than women (relative risk, 1.33; 95% CI, 1.24-1.43) but overall improved over
      time (5-year age-adjusted survival, 43% in 1979-1984 vs 52% in 1996-2000,
      P<.001). However, men and younger persons experienced larger survival gains,
      contrasting with less or no improvement for women and elderly persons.
      CONCLUSION: In this community-based cohort, the incidence of heart failure has
      not declined during 2 decades, but survival after onset of heart failure has
      increased overall, with less improvement among women and elderly persons.

PMID- 15265850
TI  - MMR vaccination and febrile seizures: evaluation of susceptible subgroups and
      long-term prognosis.
AB  - CONTEXT: The rate of febrile seizures increases following measles, mumps, and
      rubella (MMR) vaccination but it is unknown whether the rate varies according to
      personal or family history of seizures, perinatal factors, or socioeconomic
      status. Furthermore, little is known about the long-term outcome of febrile
      seizures following vaccination. OBJECTIVES: To estimate incidence rate ratios
      (RRs) and risk differences of febrile seizures following MMR vaccination within
      subgroups of children and to evaluate the clinical outcome of febrile seizures
      following vaccination. DESIGN, SETTING, AND PARTICIPANTS: A population-based
      cohort study of all children born in Denmark between January 1, 1991, and
      December 31, 1998, who were alive at 3 months; 537,171 children were followed up
      until December 31, 1999, by using data from the Danish Civil Registration System
      and 4 other national registries. MAIN OUTCOME MEASURES: Incidence of first
      febrile seizure, recurrent febrile seizures, and subsequent epilepsy. RESULTS: A
      total of 439,251 children (82%) received MMR vaccination and 17,986 children
      developed febrile seizures at least once; 973 of these febrile seizures occurred
      within 2 weeks of MMR vaccination. The RR of febrile seizures increased during
      the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55
      2.97), and thereafter was close to the observed RR for nonvaccinated children.
      The RR did not vary significantly in the subgroups of children that had been
      defined by their family history of seizures, perinatal factors, or socioeconomic
      status. At 15 to 17 months, the risk difference of febrile seizures within 2
      weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44
      1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history
      of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a
      personal history of febrile seizures. Children with febrile seizures following
      MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR,
      1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI,
      0.33-1.50) compared with children who were nonvaccinated at the time of their
      first febrile seizure. CONCLUSIONS: MMR vaccination was associated with a
      transient increased rate of febrile seizures but the risk difference was small
      even in high-risk children. The long-term rate of epilepsy was not increased in
      children who had febrile seizures following vaccination compared with children
      who had febrile seizures of a different etiology.

PMID- 15265851
TI  - Role of vitamin K2 in the development of hepatocellular carcinoma in women with
      viral cirrhosis of the liver.
AB  - CONTEXT: Previous findings indicate that vitamin K2 (menaquinone) may play a role
      in controlling cell growth. OBJECTIVE: To determine whether vitamin K2 has
      preventive effects on the development of hepatocellular carcinoma in women with
      viral cirrhosis of the liver. DESIGN, SETTING, AND PARTICIPANTS: Forty women
      diagnosed as having viral liver cirrhosis were admitted to a university hospital
      between 1996 and 1998 and were randomly assigned to the treatment or control
      group. The original goal of the trial was to assess the long-term effects of
      vitamin K2 on bone loss in women with viral liver cirrhosis. However, study
      participants also satisfied criteria required for examination of the effects of
      such treatment on the development of hepatocellular carcinoma. INTERVENTIONS: The
      treatment group received 45 mg/d of vitamin K2 (n = 21). Participants in the
      treatment and control groups received symptomatic therapy to treat ascites, if
      necessary, and dietary advice. MAIN OUTCOME MEASURE: Cumulative proportion of
      patients with hepatocellular carcinoma. RESULTS: Hepatocellular carcinoma was
      detected in 2 of the 21 women given vitamin K2 and 9 of the 19 women in the
      control group. The cumulative proportion of patients with hepatocellular
      carcinoma was smaller in the treatment group (log-rank test, P =.02). On
      univariate analysis, the risk ratio for the development of hepatocellular
      carcinoma in the treatment group compared with the control group was 0.20 (95%
      confidence interval [CI], 0.04-0.91; P =.04). On multivariate analysis with
      adjustment for age, alanine aminotransferase activity, serum albumin, total
      bilirubin, platelet count, alpha-fetoprotein, and history of treatment with
      interferon alfa, the risk ratio for the development of hepatocellular carcinoma
      in patients given vitamin K2 was 0.13 (95% CI, 0.02-0.99; P =.05). CONCLUSION:
      There is a possible role for vitamin K2 in the prevention of hepatocellular
      carcinoma in women with viral cirrhosis.

PMID- 15265852
TI  - Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary
      percutaneous coronary intervention of acute ST-segment elevation myocardial
      infarction: a meta-analysis.
AB  - CONTEXT: Glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors improve myocardial
      reperfusion and clinical outcomes of patients undergoing primary percutaneous
      coronary intervention (PCI), but optimal timing of administration remains
      unclear. No systematic reviews have comprehensively examined the effects of early
      vs delayed administration of these agents. OBJECTIVE: To perform a meta-analysis
      of randomized trials of early (prior to transfer to the catheterization
      laboratory) vs late (at the time of PCI) intravenous administration of Gp
      IIb/IIIa inhibitors in acute ST-segment elevation myocardial infarction (STEMI).
      DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Register search of the
      literature over the past 10 years; papers presented at major cardiac conferences;
      consultation with national and international colleagues as well as Gp IIb/IIIa
      inhibitor drug manufacturers; and text and journal article bibliographies. STUDY
      SELECTION AND DATA EXTRACTION: We examined trials of randomized comparisons
      between early administration at the point of initial contact (emergency
      department or ambulance) and late administration (catheterization laboratory) of
      Gp IIb/IIIa inhibitors in STEMI. Outcome data had to be available on both culprit
      artery patency evaluated by Thrombolysis in Myocardial Infarction (TIMI) flow
      grades on admission and mortality. Two authors independently reviewed abstracts
      or complete articles. Six studies met inclusion criteria. Independent data
      extraction was performed by 2 reviewers and confirmed by consensus. DATA
      SYNTHESIS: The 6 trials enrolled 931 STEMI patients treated with abciximab (3
      trials) or tirofiban (3 trials) in combination with primary PCI. TIMI grade 2 or
      3 flow (41.7% [194/465 vs 29.8% [139/466]) as well as TIMI grade 3 flow (20.3%
      [84/413] vs 12.2% [51/418]) were significantly more frequent in the early group
      compared with the late group (odds ratio [OR], 1.69; 95% confidence interval
      [CI], 1.28-2.22; P<.001; and OR, 1.85; 95% CI, 1.26-2.71; P<.001, respectively).
      The early administration of Gp IIb/IIIa inhibitors was associated with a 28%
      reduction of mortality from 4.7% to 3.4%, which was not significant but
      consistent with similar trends for reinfarction and the composite ischemic end
      point. CONCLUSIONS: In a meta-analysis of 6 randomized trials, early
      administration of Gp IIb/IIIa inhibitors in STEMI appeared to improve coronary
      patency with favorable trends for clinical outcomes. These findings are
      supportive of a strategy of facilitated PCI. Further evaluations in adequately
      powered large trials are awaited to confirm the clinical benefit of this
      strategy.

PMID- 15265854
TI  - Targeting high-risk young patients for statin therapy.

PMID- 15265853
TI  - Pharmacological management to reduce exacerbations in adults with asthma: a
      systematic review and meta-analysis.
AB  - CONTEXT: Over the last 2 decades, many new pharmacological agents have been
      introduced to reduce the growing morbidity associated with asthma, but the long
      term effects of these agents on exacerbations are unclear. OBJECTIVE: To
      systematically review and quantitatively synthesize the long-term effects of
      inhaled corticosteroids, long-acting beta2 agonists, leukotriene pathway
      modifiers/receptor antagonists, and anti-IgE therapies on clinical outcomes and
      particular clinically relevant exacerbations in adult patients with chronic
      asthma. DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were searched to
      identify relevant randomized controlled trials and systematic reviews published
      from January 1, 1980, to April 30, 2004. We identified additional studies by
      searching bibliographies of retrieved articles and contacting experts in the
      field. STUDY SELECTION AND DATA EXTRACTION: Included trials were double-blind,
      had follow-up periods of at least 3 months, and contained data on exacerbations
      and/or forced expiratory volume in 1 second. The effects of interventions were
      compared with placebo, short-acting beta2 agonists, or each other. DATA
      SYNTHESIS: Inhaled corticosteroids were most effective, reducing exacerbations by
      nearly 55% compared with placebo or short-acting beta2 agonists (relative risk
      [RR], 0.46; 95% confidence interval [CI], 0.34-0.62; P<.001 for heterogeneity).
      Compared with placebo, the use of long-acting beta2 agonists was associated with
      25% fewer exacerbations (RR, 0.75; 95% CI, 0.64-0.88; P =.43 for heterogeneity);
      when added to inhaled corticosteroids, there was a 26% reduction above that
      achieved by steroid monotherapy (RR, 0.74; 95% CI, 0.61-0.91; P =.07 for
      heterogeneity). Combination therapy was associated with fewer exacerbations than
      was increasing the dose of inhaled corticosteroids (RR, 0.86; 95% CI, 0.76-0.96;
      P =.65 for heterogeneity). Compared with placebo, leukotriene modifiers/receptor
      antagonists reduced exacerbations by 41% (RR, 0.59; 95% CI, 0.49-0.71; P =.44 for
      heterogeneity) but were less effective than inhaled corticosteroids (RR, 1.72;
      95% CI, 1.28-2.31; P =.91 for heterogeneity). Use of monoclonal anti-IgE
      antibodies with concomitant inhaled corticosteroid therapy was associated with
      45% fewer exacerbations (RR, 0.55; 95% CI, 0.45-0.66; P =.15 for heterogeneity).
      CONCLUSIONS: Inhaled corticosteroids are the single most effective therapy for
      adult patients with asthma. However, for those unable or unwilling to take
      corticosteroids, the use of leukotriene modifiers/receptor agonists appears
      reasonable. Long-acting beta2 agonists may be added to corticosteroids for those
      who remain symptomatic despite low-dose steroid therapy. Anti-IgE therapy may be
      considered as adjunctive therapy for young adults with asthma who have clear
      evidence of allergies and elevated serum IgE levels.

PMID- 15265855
TI  - Suicide risk and the SSRIs.

PMID- 15265856
TI  - JAMA patient page. Adult asthma.

PMID- 15265857
TI  - Site-directed mutagenesis of the distal basic cluster of pancreatic bile salt
      dependent lipase.
AB  - Previous studies have postulated the presence of two bile salt-binding sites
      regulating the activity of the pancreatic bile salt-dependent lipase. One of
      these sites, located in an N-terminal basic cluster, has been identified as the
      specific bile salt-binding site. Interaction of primary bile salts with this
      proximal site induces the formation of a micellar binding site from a pre
      existing nonspecific or pre-micellar bile salt-binding site. Here we have
      investigated the functional significance of another basic cluster comprised of
      amino acid residues Arg(423), Lys(429), Arg(454), Arg(458), and Lys(462), distal
      from the catalytic site. For this purpose these residues were mutagenized in Ile
      or Ala residues. The mutagenized enzyme lost activity on both soluble and
      emulsified substrates in the presence of bile salts. However, in the absence of
      bile salts, the mutagenized enzyme displayed the same activity on soluble
      substrate as the wild-type recombinant enzyme. Consequently, the distal basic
      cluster may represent the nonspecific (or pre-micellar) bile salt-binding site
      susceptible to accommodate primary and secondary bile salts. According to the
      literature, tyrosine residue(s) should participate in this site. Therefore, two
      tyrosine residues, Tyr(427) and Tyr(453), associated with the distal basic
      cluster were also mutagenized. Each tyrosine substitution to serine did not
      inhibit the enzyme activity on soluble substrate, independently of the presence
      of primary or secondary bile salts. However, the enzyme activity on cholesteryl
      oleate solubilized in primary bile salt micelles was decreased by mutations
      substantiating that these residues are part of the nonspecific bile salt-binding
      site.

PMID- 15265858
TI  - A trimeric quaternary structure is conserved in bacterial and human glutamate
      transporters.
AB  - Neuronal and glial glutamate transporters play a central role in the termination
      of synaptic transmission and in extracellular glutamate homeostasis in the
      mammalian central nervous system. They are known to be multimers; however, the
      number of subunits forming a functional transporter is controversial. We studied
      the subunit stoichiometry of two distantly related glutamate transporters, the
      human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter
      from Escherichia coli, ecgltP. Using blue native polyacrylamide gel
      electrophoresis, analysis of concatenated transporters, and chemical cross
      linking, we demonstrated that human and prokaryotic glutamate transporters
      expressed in Xenopus laevis oocytes or in mammalian cells are assembled as
      trimers composed of three identical subunits. In an inducible mammalian cell line
      expressing hEAAT2 the glutamate uptake currents correlate to the amount of
      trimeric transporters. Overexpression and purification of ecgltP in E. coli
      resulted in a homogenous population of trimeric transporters that were functional
      after reconstitution in lipid vesicles. Our results indicate that an
      evolutionarily conserved trimeric quaternary structure represents the sole native
      and functional state of glutamate transporters.

PMID- 15265859
TI  - Delayed hepatocellular mitotic progression and impaired liver regeneration in
      early growth response-1-deficient mice.
AB  - The early growth response-1 transcription factor (Egr-1) is induced as part of
      the immediate-early gene expression response during early liver regeneration. In
      the studies reported here the functional significance of EGR-1 expression during
      liver regeneration was examined by characterizing the hepatic regenerative
      response to partial hepatectomy in Egr-1 null mice. The results of these studies
      showed that liver regeneration in Egr-1 null mice is impaired. Although
      activation of interleukin-6-STAT3 signaling, regulation of expression of hepatic
      C/ebpalpha, C/ebpbeta, cyclin D, and cyclin E and progression through the first
      wave of hepatocellular DNA synthesis occurred appropriately following partial
      hepatectomy in Egr-1 null mice, subsequent signaling events and cell cycle
      progression after the first round of DNA synthesis were deranged. This
      derangement was characterized by increased activation of the p38 mitogen
      activated protein kinase and inhibition of hepatocellular metaphase-to-anaphase
      mitotic progression. Together these observations suggest that EGR-1 is an
      important regulator of hepatocellular mitotic progression. In support of this,
      microarray-based gene expression analysis showed that induction of expression of
      the cell division cycle 20 gene (Cdc20), a key regulator of the mitotic anaphase
      promoting complex, is significantly reduced in Egr-1 null mice. Taken together
      these data define a novel functional role for EGR-1 in regulating hepatocellular
      mitotic progression through the spindle assembly checkpoint during liver
      regeneration.

PMID- 15265860
TI  - The structural basis for substrate promiscuity in 2-keto-3-deoxygluconate
      aldolase from the Entner-Doudoroff pathway in Sulfolobus solfataricus.
AB  - The hyperthermophilic Archaea Sulfolobus solfataricus grows optimally above 80
      degrees C and metabolizes glucose by a non-phosphorylative variant of the Entner
      Doudoroff pathway. In this pathway glucose dehydrogenase and gluconate
      dehydratase catalyze the oxidation of glucose to gluconate and the subsequent
      dehydration of gluconate to D-2-keto-3-deoxygluconate (KDG). KDG aldolase (KDGA)
      then catalyzes the cleavage of KDG to D-glyceraldehyde and pyruvate. It has
      recently been shown that all the enzymes of this pathway exhibit a catalytic
      promiscuity that also enables them to be used for the metabolism of galactose.
      This phenomenon, known as metabolic pathway promiscuity, depends crucially on the
      ability of KDGA to cleave KDG and D-2-keto-3-deoxygalactonate (KDGal), in both
      cases producing pyruvate and D-glyceraldehyde. In turn, the aldolase exhibits a
      remarkable lack of stereoselectivity in the condensation reaction of pyruvate and
      D-glyceraldehyde, forming a mixture of KDG and KDGal. We now report the structure
      of KDGA, determined by multiwavelength anomalous diffraction phasing, and confirm
      that it is a member of the tetrameric N-acetylneuraminate lyase superfamily of
      Schiff base-forming aldolases. Furthermore, by soaking crystals of the aldolase
      at more than 80 degrees C below its temperature activity optimum, we have been
      able to trap Schiff base complexes of the natural substrates pyruvate, KDG,
      KDGal, and pyruvate plus D-glyceraldehyde, which have allowed rationalization of
      the structural basis of promiscuous substrate recognition and catalysis. It is
      proposed that the active site of the enzyme is rigid to keep its thermostability
      but incorporates extra functionality to be promiscuous.

PMID- 15265861
TI  - Mitochondrial reactive oxygen species control the transcription factor CHOP
      10/GADD153 and adipocyte differentiation: a mechanism for hypoxia-dependent
      effect.
AB  - Recent reports emphasize the importance of mitochondria in white adipose tissue
      biology. In addition to their crucial role in energy homeostasis, mitochondria
      are the main site of reactive oxygen species generation. When moderately
      produced, they function as physiological signaling molecules. Thus, mitochondrial
      reactive oxygen species trigger hypoxia-dependent gene expression. Therefore the
      present study tested the implication of mitochondrial reactive oxygen species in
      adipocyte differentiation and their putative role in the hypoxia-dependent effect
      on this differentiation. Pharmacological manipulations of mitochondrial reactive
      oxygen species generation demonstrate a very strong and negative correlation
      between changes in mitochondrial reactive oxygen species and adipocyte
      differentiation of 3T3-F442A preadipocytes. Moreover, mitochondrial reactive
      oxygen species positively and specifically control expression of the adipogenic
      repressor CHOP-10/GADD153. Hypoxia (1% O2) strongly increased reactive oxygen
      species generation, hypoxia-inducible factor-1 and CHOP-10/GADD153 expression,
      and inhibited adipocyte differentiation. All of these hypoxia-dependent effects
      were partly prevented by antioxidants. By using hypoxia-inducible factor-1alpha
      (HIF-1alpha)-deficient mouse embryonic fibroblasts, HIF-1alpha was shown not to
      be required for hypoxia-mediated CHOP-10/GADD153 induction. Moreover, the
      comparison of hypoxia and CoCl2 effects on adipocyte differentiation of wild type
      or HIF-1alpha deficient mouse embryonic fibroblasts suggests the existence of at
      least two pathways dependent or not on the presence of HIF-1alpha. Together,
      these data demonstrate that mitochondrial reactive oxygen species control CHOP
      10/GADD153 expression, are antiadipogenic signaling molecules, and trigger
      hypoxia-dependent inhibition of adipocyte differentiation.

PMID- 15265862
TI  - Transcriptional regulation of the mouse gene encoding the alpha-4 subunit of the
      GABAA receptor.
AB  - The gamma-aminobutyric acid type A receptors (GABAA-Rs) mediate fast inhibitory
      synaptic transmission in the brain. The alpha4 subunit of the GABAA-R confers
      distinct pharmacological properties on the receptor and its expression pattern
      exhibits plasticity in response to physiological and pharmacological stimuli,
      including withdrawal from progesterone and alcohol. We have analyzed the promoter
      region of the mouse GABRA4 gene that encodes the alpha4 subunit and found that
      the promoter has multiple transcriptional initiation sites and lacks a TATA box.
      The minimal promoter for GABRA4 spans the region between -444 to -19 bp relative
      to the coding ATG and shows high activity in cultured mouse cortical neurons.
      Both Sp3 and Sp4 transcription factors can interact with the two Sp1 binding
      sites within the minimal promoter and are critical for maximal activity of the
      promoter in neurons.

PMID- 15265863
TI  - Crystal structure of a bacterial type III polyketide synthase and enzymatic
      control of reactive polyketide intermediates.
AB  - In bacteria, a structurally simple type III polyketide synthase (PKS) known as
      1,3,6,8-tetrahydroxynaphthlene synthase (THNS) catalyzes the iterative
      condensation of five CoA-linked malonyl units to form a pentaketide intermediate.
      THNS subsequently catalyzes dual intramolecular Claisen and aldol condensations
      of this linear intermediate to produce the fused ring tetrahydroxynaphthalene
      (THN) skeleton. The type III PKS-catalyzed polyketide extension mechanism,
      utilizing a conserved Cys-His-Asn catalytic triad in an internal active site
      cavity, is fairly well understood. However, the mechanistic basis for the unusual
      production of THN and dual cyclization of its malonyl-primed pentaketide is
      obscure. Here we present the first bacterial type III PKS crystal structure, that
      of Streptomyces coelicolor THNS, and identify by mutagenesis, structural
      modeling, and chemical analysis the unexpected catalytic participation of an
      additional THNS-conserved cysteine residue in facilitating malonyl-primed
      polyketide extension beyond the triketide stage. The resulting new mechanistic
      model, involving the use of additional cysteines to alter and steer polyketide
      reactivity, may generally apply to other PKS reaction mechanisms, including those
      catalyzed by iterative type I and II PKS enzymes. Our crystal structure also
      reveals an unanticipated novel cavity extending into the "floor" of the
      traditional active site cavity, providing the first plausible structural and
      mechanistic explanation for yet another unusual THNS catalytic activity: its
      previously inexplicable extra polyketide extension step when primed with a long
      acyl starter. This tunnel allows for selective expansion of available active site
      cavity volume by sequestration of aliphatic starter-derived polyketide tails, and
      further suggests another distinct protection mechanism involving maintenance of a
      linear polyketide conformation.

PMID- 15265864
TI  - An antibody specific for coagulation factor IX enhances the activity of the
      intrinsic factor X-activating complex.
AB  - During hemostasis the zymogen factor X (FX) is converted into its enzymatically
      active form factor Xa by the intrinsic FX-activating complex. This complex
      consists of the protease factor IXa (FIXa) that assembles, together with its
      cofactor, factor VIIIa, on a phospholipid surface. We have studied the functional
      properties of a FIXa-specific monoclonal antibody, 224AE3, which has the
      potential to enhance intrinsic FX activation. Binding of the antibody to FIXa
      improved the catalytic properties of the intrinsic FX-activating complex in two
      ways: (i) factor VIIIa bound to the FIXa-antibody complex with a more than 18
      fold higher affinity than to FIXa, and (ii) the turnover number (kcat) of the
      enzyme complex increased 2- to 3-fold whereas the Km for FX remained unaffected.
      The ability of 224AE3 to increase the FXa-generation potential (called the
      "booster effect") was confirmed in factor VIII (FVIII)-depleted plasma, which was
      supplemented with different amounts of recombinant FVIII. In the presence of
      antibody 224AE3 the coagulant activity was increased 2-fold at physiological
      FVIII concentration and up to 15-fold at low FVIII concentrations. The booster
      effect that we describe demonstrates the ability of antibodies to function as an
      additional cofactor in an enzymatic reaction and might open up a new principle
      for improving the treatment of hemophilia.

PMID- 15265865
TI  - Synapsin is a novel Rab3 effector protein on small synaptic vesicles. I.
      Identification and characterization of the synapsin I-Rab3 interactions in vitro
      and in intact nerve terminals.
AB  - Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to
      regulate the availability of synaptic vesicles for exocytosis by binding to both
      synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent
      manner. Although the above-mentioned observations strongly support a pre-docking
      role of the synapsins in the assembly and maintenance of a reserve pool of
      synaptic vesicles, recent results suggest that the synapsins may also be involved
      in some later step of exocytosis. In order to investigate additional interactions
      of the synapsins with nerve terminal proteins, we have employed phage display
      library technology to select peptide sequences binding with high affinity to
      synapsin I. Antibodies raised against the peptide YQYIETSMQ (syn21) specifically
      recognized Rab3A, a synaptic vesicle-specific small G protein implicated in
      multiple steps of exocytosis. The interaction between synapsin I and Rab3A was
      confirmed by photoaffinity labeling experiments on purified synaptic vesicles and
      by the formation of a chemically cross-linked complex between synapsin I and
      Rab3A in intact nerve terminals. Synapsin I could be effectively co-precipitated
      from synaptosomal extracts by immobilized recombinant Rab3A in a GTP-dependent
      fashion. In vitro binding assays using purified proteins confirmed the binding
      preference of synapsin I for Rab3A-GTP and revealed that the COOH-terminal
      regions of synapsin I and the Rab3A effector domain are required for the
      interaction with Rab3A to occur. The data indicate that synapsin I is a novel
      Rab3 interactor on synaptic vesicles and suggest that the synapsin-Rab3
      interaction may participate in the regulation of synaptic vesicle trafficking
      within the nerve terminals.

PMID- 15265866
TI  - The role of active site glutamate residues in catalysis of Rhodobacter capsulatus
      xanthine dehydrogenase.
AB  - Xanthine dehydrogenase (XDH) from the bacterium Rhodobacter capsulatus catalyzes
      the hydroxylation of xanthine to uric acid with NAD+ as the electron acceptor. R.
      capsulatus XDH forms an (alphabeta)2 heterotetramer and is highly homologous to
      homodimeric eukaryotic xanthine oxidoreductases. Here we first describe reductive
      titration and steady state kinetics on recombinant wild-type R. capsulatus XDH
      purified from Escherichia coli, and we then proceed to evaluate the catalytic
      importance of the active site residues Glu-232 and Glu-730. The steady state and
      rapid reaction kinetics of an E232A variant exhibited a significant decrease in
      both kcat and kred as well as increased Km and Kd values as compared with the
      wild-type protein. No activity was determined for the E730A, E730Q, E730R, and
      E730D variants in either the steady state or rapid reaction experiments,
      indicating at least a 10(7) decrease in catalytic effectiveness for this variant.
      This result is fully consistent with the proposed role of this residue as an
      active site base that initiates catalysis.

PMID- 15265867
TI  - Negative regulation of phosphatidylinositol 4,5-bisphosphate levels by the INP51
      associated proteins TAX4 and IRS4.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) is an important second
      messenger in signaling pathways in organisms ranging from yeast to mammals, but
      the regulation of PI(4,5)P(2) levels remains unclear. Here we present evidence
      that PI(4,5)P(2) levels in Saccharomyces cerevisiae are down-regulated by the
      homologous and functionally redundant proteins TAX4 and IRS4. The EPS15 homology
      domain-containing proteins TAX4 and IRS4 bind and activate the PI(4,5)P 5
      phosphatase INP51 via an Asn-Pro-Phe motif in INP51. Furthermore, the INP51
      TAX4/IRS4 complex negatively regulates the cell integrity pathway. Thus, TAX4 and
      IRS4 are novel regulators of PI(4,5)P(2) and PI(4,5)P(2)-dependent signaling. The
      interaction between TAX4/IRS4 and INP51 is analogous to the association of EPS15
      with the 5-phosphatase synaptojanin 1 in mammalian cells, suggesting that EPS15
      is an activator of synaptojanin 1.

PMID- 15265868
TI  - Synapsin is a novel Rab3 effector protein on small synaptic vesicles. II.
      Functional effects of the Rab3A-synapsin I interaction.
AB  - Synapsins, a family of neuron-specific phosphoproteins that play an important
      role in the regulation of synaptic vesicle trafficking and neurotransmitter
      release, were recently demonstrated to interact with the synaptic vesicle
      associated small G protein Rab3A within nerve terminals (Giovedi, S., Vaccaro,
      P., Valtorta, F., Darchen, F., Greengard, P., Cesareni, G., and Benfenati, F.
      (2004) J. Biol. Chem. 279, 43760-43768). We have analyzed the functional
      consequences of this interaction on the biological activities of both proteins
      and on their subcellular distribution within nerve terminals. The presence of
      synapsin I stimulated GTP binding and GTPase activity of both purified and
      endogenous synaptic vesicle-associated Rab3A. Conversely, Rab3A inhibited
      synapsin I binding to F-actin, as well as synapsin-induced actin bundling and
      vesicle clustering. Moreover, the amount of Rab3A associated with synaptic
      vesicles was decreased in synapsin knockout mice, and the presence of synapsin I
      prevented RabGDI-induced Rab3A dissociation from synaptic vesicles. The results
      indicate that an interaction between synapsin I and Rab3A exists on synaptic
      vesicles that modulates the functional properties of both proteins. Given the
      well recognized importance of both synapsins and Rab3A in synaptic vesicles
      exocytosis, this interaction is likely to play a major role in the modulation of
      neurotransmitter release.

PMID- 15265869
TI  - Uncoupling of calcium channel alpha1 and beta subunits in developing neurons.
AB  - Calcium channel beta subunits are key modulators of calcium channel function and
      membrane targeting of the pore-forming alpha1 subunit. Here we show that an
      invertebrate (Lymnaea stagnalis) homolog of P/Q- and N-type calcium channels
      (LCav2), although colocalized with beta subunits in synapses of mature neurons,
      is physically uncoupled from the beta subunits in the leading edge of growth
      cones of outgrowing neurons. Moreover, LCav2 channels that mediate transmitter
      release in mature synapses also participate in neuronal outgrowth in growth
      cones. The differential association of beta subunits with synaptic calcium
      channels and those expressed in emergent neuronal growth suggests that beta
      subunits may play a role in the transformation of Cav2 calcium channel function
      in immature neurons and mature synapses.

PMID- 15265870
TI  - A single catalytically active subunit in the multimeric Sulfolobus shibatae CCA
      adding enzyme can carry out all three steps of CCA addition.
AB  - The CCA-adding enzyme ATP(CTP):tRNA nucleotidyltransferase builds and repairs the
      3'-terminal CCA sequence of tRNA. Although this unusual RNA polymerase has no
      nucleic acid template, it can construct the CCA sequence one nucleotide at a time
      using CTP and ATP as substrates. We found previously that tRNA does not
      translocate along the enzyme during CCA addition (Yue, D., Weiner, A. M., and
      Maizels, N. (1998) J. Biol. Chem. 273, 29693-29700) and that a single
      nucleotidyltransferase motif adds all three nucleotides (Shi, P.-Y., Maizels, N.,
      and Weiner, A. M. (1998) EMBO J. 17, 3197-3206). Intriguingly, the CCA-adding
      enzyme from the archaeon Sulfolobus shibatae is a homodimer that forms a tetramer
      upon binding two tRNAs. We therefore asked whether the active form of the S.
      shibatae enzyme might have two quasi-equivalent active sites, one adding CTP and
      the other ATP. Using an intersubunit complementation approach, we demonstrate
      that the dimer is active and that a single catalytically active subunit can carry
      out all three steps of CCA addition. We also locate one UV light-induced tRNA
      cross-link on the enzyme structure and provide evidence suggesting the location
      of another. Our data rule out shuttling models in which the 3'-end of the tRNA
      shuttles from one quasi-equivalent active site to another, demonstrate that tRNA
      induced tetramerization is not required for CCA addition, and support a role for
      the tail domain of the enzyme in tRNA binding.

PMID- 15265871
TI  - Activation of the AMP-activated protein kinase by the anti-diabetic drug
      metformin in vivo. Role of mitochondrial reactive nitrogen species.
AB  - Metformin, one of the most commonly used drugs for the treatment of type II
      diabetes, was recently found to exert its therapeutic effects, at least in part,
      by activating the AMP-activated protein kinase (AMPK). However, the site of its
      action, as well as the mechanism to activate AMPK, remains elusive. Here we
      report how metformin activates AMPK. In cultured bovine aortic endothelial cells,
      metformin dose-dependently activated AMPK in parallel with increased detection of
      reactive nitrogen species (RNS). Further, either depletion of mitochondria or
      adenoviral overexpression of superoxide dismutases, as well as inhibition of
      nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and
      activities of AMPK, implicating that activation of AMPK by metformin might be
      mediated by the mitochondria-derived RNS. Furthermore, administration of
      metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted
      in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in
      those of endothelial nitric-oxide synthase (eNOS) knockout mice in which
      metformin had no effect on 3-nitrotyrosine staining. Because the eNOS knockout
      mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole
      4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated
      by metformin is required for AMPK activation in vivo. In addition, metformin
      significantly increased the co-immunoprecipitation of AMPK and its upstream
      kinase, LKB1, in C57BL6 mice administered to metformin in vivo. Using
      pharmacological and genetic inhibitors, we found that inhibition of either c-Src
      or PI3K abolished AMPK that was enhanced by metformin. We conclude that
      activation of AMPK by metformin might be mediated by mitochondria-derived RNS,
      and activation of the c-Src/PI3K pathway might generate a metabolite or other
      molecule inside the cell to promote AMPK activation by the LKB1 complex.

PMID- 15265872
TI  - The functional domains of bacteriophage t4 terminase.
AB  - The packaging of double-stranded genomic DNA into some viral and all
      bacteriophage capsids is driven by powerful molecular motors. In bacteriophage
      T4, the motor consists of the portal protein assembly composed of twelve copies
      of gene product 20 (gp20, 61 kDa) and an oligomeric terminase complex composed of
      gp16 (18 kDa) and gp17 (70 kDa). The packaging motor drives the 171-kbp T4 DNA
      into the capsid utilizing the free energy of ATP hydrolysis. Evidence suggests
      that gp17 is the key component of the motor; it exhibits ATPase, nuclease, and in
      vitro DNA-packaging activities. The N- and C-terminal halves of gp17 were
      expressed and purified to homogeneity and found to have ATPase and nuclease
      activities, respectively. The N-terminal domain exhibited 2-3-fold higher Kcat
      values for gp16-stimulated ATPase than the full-length gp17. Neither of the
      domains, individually or together, exhibited in vitro DNA-packaging activity,
      suggesting that communication between the domains is essential for DNA packaging.
      The domains, in particular the C-terminal domain or a mixture of both the N- and
      C-terminal domains, inhibited in vitro DNA packaging that is catalyzed by full
      length gp17. In conjunction with genetic evidence, these data suggest that the
      domains compete with the full-length gp17 for binding sites on the portal
      protein. A model for the assembly of the T4 DNA-packaging machine is presented.

PMID- 15265873
TI  - Chain termination and inhibition of Saccharomyces cerevisiae poly(A) polymerase
      by C-8-modified ATP analogs.
AB  - The nucleotide substrate specificity of yeast poly(A) polymerase (yPAP) toward
      various C-2- and C-8-modified ATP analogs was examined. 32P-Radiolabeled RNA
      oligonucleotide primers were incubated with yPAP in the absence of ATP to assay
      polyadenylation using unnatural ATP substrates. The C-2-modified ATP analogs 2
      amino-ATP and 2-chloro (Cl)-ATP were excellent substrates for yPAP. 8-Amino-ATP,
      8-azido-ATP, and 8-aza-ATP all produced chain termination of polyadenylation, and
      no primer extension was observed with the C-8-halogenated derivatives 8-Br-ATP
      and 8-Cl-ATP. The effects of modified ATP analogs on ATP-dependent poly(A) tail
      synthesis by yPAP were also examined. Whereas C-2 substitution (2-amino-ATP and 2
      Cl-ATP) had little effect on poly(A) tail length, C-8 substitution produced
      moderate (8-amino-ATP, 8-azido-ATP, and 8-aza-ATP) to substantial (8-Br-ATP and 8
      Cl-ATP) reduction in poly(A) tail length. To model the biochemical consequences
      of 8-Cl-Ado incorporation into RNA primers, a synthetic RNA primer containing a
      3'-terminal 8-Cl-AMP residue was prepared. Polyadenylation of this modified RNA
      primer by yPAP in the presence of ATP was blocked completely. To probe potential
      mechanisms of inhibition, two-dimensional NMR spectroscopy experiments were used
      to examine the conformation of two C-8-modified AMP nucleotides, 8-Cl-AMP and 8
      amino-AMP. C-8 substitution in adenosine analogs shifted the ribose sugar pucker
      equilibrium to favor the DNA-like C-2'-endo form over the C-3'-endo (RNA-like)
      conformation, which suggests a potential mechanism for polyadenylation inhibition
      and chain termination. Base-modified ATP analogs may exert their biological
      effects through polyadenylation inhibition and thus may provide useful tools for
      investigating polyadenylation biochemistry within cells.

PMID- 15265874
TI  - Making the connection: antibody responsiveness and MHC genes.

PMID- 15265875
TI  - Genetic control of the antibody responses: relationship between immune response
      and histocompatibility (H-2) type. 1969.

PMID- 15265876
TI  - Cysteinyl leukotrienes and their receptors: cellular distribution and function in
      immune and inflammatory responses.
AB  - The cysteinyl leukotrienes (cys-LTs) are a family of potent bioactive lipids that
      act through two structurally divergent G protein-coupled receptors, termed the
      CysLT(1) and CysLT(2) receptors. The cloning and characterization of these two
      receptors has not only reconciled findings of previous pharmacologic profiling
      studies of contractile tissues, but also has uncovered their expression on a wide
      array of circulating and tissue-dwelling leukocytes. With the development of
      receptor-selective reagents, as well as mice lacking critical biosynthetic
      enzymes, transporter proteins, and the CysLT(1) receptor, diverse functions of
      cys-LTs and their receptors in immune and inflammatory responses have been
      identified. We review cys-LT biosynthesis; the molecular biology and distribution
      of the CysLT(1) and CysLT(2) receptors; the functions of cys-LTs and their
      receptors in the recruitment and activation of effector leukocytes and induction
      of adaptive immunity; and the development of fibrosis and airway remodeling in
      animal models of lung injury and allergic inflammation.

PMID- 15265877
TI  - Cutting edge: Membrane nanotubes connect immune cells.
AB  - We present evidence that nanotubular highways, or membrane nanotubes, facilitate
      a novel mechanism for intercellular communication in the immune system. Nanotubes
      were seen to connect multiple cells together and were readily formed between a
      variety of cell types, including human peripheral blood NK cells, macrophages,
      and EBV-transformed B cells. Nanotubes could be created upon disassembly of the
      immunological synapse, as cells move apart. Thus, nanotubular networks could be
      assembled from transient immunological synapses. Nanotubes were seen to contain
      GFP-tagged cell surface class I MHC protein expressed in one of the connected
      cells. Moreover, GPI-conjugated to GFP originating from one cell was transferred
      onto the surface of another at the connection with a nanotube. Thus, nanotubes
      can traffic cell surface proteins between immune cells over many tens of microns.
      Determining whether there are physiological functions for nanotubes is an
      intriguing new goal for cellular immunology.

PMID- 15265878
TI  - Cutting Edge: Innate production of IFN-gamma by NK cells is independent of
      epigenetic modification of the IFN-gamma promoter.
AB  - The ability of NK and T cells to produce IFN-gamma is critical for resistance to
      numerous intracellular pathogens but the kinetics of these responses differ.
      Consistent with this is a requirement for naive T cells to become activated and
      undergo proliferation-dependent epigenetic changes to the IFN-gamma locus that
      allow them to produce IFN-gamma. The data presented here reveal that unlike T
      cells, murine NK cells produce IFN-gamma under conditions of short-term cytokine
      stimulation, and these events are independent of proliferation and cell cycle
      progression. Furthermore, analysis of the IFN-gamma locus in NK cells reveals
      that this locus is constitutively demethylated. The finding that NK cells do not
      need to remodel the IFN-gamma locus to produce IFN-gamma, either because they do
      not exhibit epigenetic repression or they have undergone prior remodeling during
      development, provides a molecular basis for the innate and adaptive regulation of
      the production of this cytokine.

PMID- 15265879
TI  - Termination of antigen-specific immunity by CD95 ligand (Fas ligand) and IL-10.
AB  - Following elimination of a foreign invader, the immune system must return to its
      normal quiescent levels. This process requires removal of reactive immune cells
      when they are no longer needed. We have explored the role of Fas/Fas ligand
      (FasL) in terminating immunity and demonstrate that mice defective in these
      proteins have prolonged immune responses. Studies demonstrate that termination of
      immunity occurs via the interaction of Fas(+) lymphoid cells with FasL(+)
      nonlymphoid cells at the site of Ag challenge. Our results also show that FasL is
      absent in quiescent tissue but is rapidly up-regulated during the local immune
      reaction. This occurs through the production of IL-10. Thus, FasL and IL-10 work
      in concert to eliminate inflammatory cells and control the duration of an immune
      response.

PMID- 15265880
TI  - Antigen-processing machinery in human dendritic cells: up-regulation by
      maturation and down-regulation by tumor cells.
AB  - It has been known for some time that functional properties of dendritic cells
      (DC), and in particular their ability to process and present Ags to T cells, can
      be modulated by cytokine-induced maturation and by interactions with tumor cells.
      However, the molecular basis for these functional changes is unknown. We have
      investigated whether changes in expression of Ag-processing machinery (APM)
      components in DC are associated with alterations in their ability to present
      tumor-derived Ags to T cells. Using a panel of mAbs specific for individual APM
      components and a quantitative flow cytometry-based method, the level of APM
      components was measured in DC generated from peripheral blood monocytes of 12
      normal donors and of 8 patients with cancer. Immature DC had significantly lower
      (p < 0.01) expression of MB1, LMP-7, LMP-10, TAP-1, and tapasin than mature DC.
      However, maturation in the presence of a cytokine mixture up-regulated expression
      of these components in DC obtained from normal donors and patients with cancer.
      Immature DC incubated with tumor cells had significantly lower (p < 0.001)
      expression of MB1, LMP-2, LMP-7, LMP-10, and endoplasmic reticulum p75 than
      controls. These changes were associated with a decreased ability of DC to present
      tumor-derived Ags to T cells, as measured in ELISPOT assays and with apoptosis of
      T cells in DC-T cell cultures. Thus, tumor cells have a significant suppressive
      effect on DC; however, ex vivo maturation of DC derived from patients with cancer
      in a polarizing cytokine mix restores normal expression of APM components and Ag
      processing capabilities.

PMID- 15265881
TI  - Regulation of IFN regulatory factor-7 and IFN-alpha production by enveloped virus
      and lipopolysaccharide in human plasmacytoid dendritic cells.
AB  - Human plasmacytoid dendritic cells (PDC) are a major source of IFN-alpha upon
      exposure to enveloped viruses and TLR-7 and TLR-9 ligands. Although IFN
      regulatory factor-7 (IRF-7) is known to play an essential role in virus-activated
      transcription of IFN-alpha genes, the molecular mechanisms of IFN-alpha
      production in human PDC remain poorly understood. We and others have recently
      reported high constitutive levels of IRF-7 expression in PDC as compared with
      other PBMC. In this study, we demonstrate that both LPS and HSV up-regulate the
      expression of IRF-7 in PDC, and that this enhancement of IRF-7 is dependent on NF
      kappa B activation. The NF-kappa B inhibitors MG132 and
      pyrrolidinedithiocarbamate efficiently inhibited the induction of IRF-7 by HSV or
      LPS, and also down-regulated the constitutive expression of IRF-7 in PDC and
      blocked the HSV-induced production of IFN-alpha. In addition, we found that
      nuclear translocation of IRF-7 occurred rapidly in response to HSV stimulation,
      but not in response to LPS, which is consistent with the stimulation of IFN-alpha
      production by virus and not by LPS. Although LPS by itself was not able to induce
      IFN-alpha production, it led to rapid up-regulation of TLR-4 on PDC and increased
      the magnitude and accelerated the kinetics of HSV-induced IFN-alpha production in
      PDC, providing a mechanism that might be operative in a scenario of mixed
      infection. In contrast to the current concept of IFN-alpha regulation established
      in cell lines, this study strongly supports the immediate availability of high
      constitutive levels of IRF-7 expression in PDC, and suggests an activation
      required for IRF-7 that contributes to IFN-alpha production in virus-stimulated
      PDC.

PMID- 15265882
TI  - Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II
      antigen presentation.
AB  - The MHC class II-like molecule HLA-DM (DM) (H-2M in mice) catalyzes the exchange
      of CLIP for antigenic peptides in the endosomes of APCs. HLA-DO (DO) (H-2O in
      mice) is another class II-like molecule that is expressed in B cells, but not in
      other APCs. Studies have shown that DO impairs or modifies the peptide exchange
      activity of DM. To further evaluate the role of DO in Ag processing and
      presentation, we generated transgenic mice that expressed the human HLA-DOA and
      HLA-DOB genes under the control of a dendritic cell (DC)-specific promoter. Our
      analyses of DCs from these mice showed that as DO levels increased, cell surface
      levels of A(b)-CLIP also increased while class II-peptide levels decreased. The
      presentation of some, but not all, exogenous Ags to T cells or T hybridomas was
      significantly inhibited by DO. Surprisingly, H-2M accumulated in DO-expressing
      DCs and B cells, suggesting that H-2O/DO prolongs the half-life of H-2M. Overall,
      our studies showed that DO expression impaired H-2M function, resulting in Ag
      specific down-modulation of class II Ag processing and presentation.

PMID- 15265883
TI  - In vivo pattern of lipopolysaccharide and anti-CD3-induced NF-kappa B activation
      using a novel gene-targeted enhanced GFP reporter gene mouse.
AB  - NF-kappa B is a family of transcription factors involved in regulating cell
      death/survival, differentiation, and inflammation. Although the transactivation
      ability of NF-kappa B has been extensively studied in vitro, limited information
      is available on the spatial and temporal transactivation pattern in vivo. To
      investigate the kinetics and cellular localization of NF-kappa B-induced
      transcription, we created a transgenic mouse expressing the enhanced GFP (EGFP)
      under the transcriptional control of NF-kappa B cis elements (cis-NF-kappa
      B(EGFP)). A gene-targeting approach was used to insert a single copy of a NF
      kappa B-dependent EGFP reporter gene 5' of the X-linked hypoxanthine
      phosphoribosyltransferase locus in mouse embryonic stem cells. Embryonic
      fibroblasts, hepatic stellate cells, splenocytes, and dendritic cells isolated
      from cis-NF-kappa B(EGFP) mice demonstrated a strong induction of EGFP in
      response to LPS, anti-CD3, or TNF-alpha that was blocked by the NF-kappa B
      inhibitors BAY 11-7082 and NEMO-binding peptide. Chromatin immunoprecipitation
      analysis demonstrated RelA binding to the cis-NF-kappa B(EGFP) promoter.
      Adenoviral delivery of NF-kappa B-inducing kinase strongly induced EGFP
      expression in the liver of cis-NF-kappa B(EGFP) mice. Similarly, mice injected
      with anti-CD3 or LPS showed increased EGFP expression in mononuclear cells, lymph
      node, spleen, and liver as measured by flow cytometry and/or fluorescence
      microscopy. Using whole organ imaging, LPS selectively induced EGFP expression in
      the duodenum and proximal jejunum, but not in the ileum and colon. Confocal
      analysis indicated EGFP expression was primarily found in lamina propria
      mononuclear cells. In summary, the cis-NF-kappa B(EGFP) mouse will serve as a
      valuable tool to address multiple questions regarding the cell-specific and real
      time activation of NF-kappa B during normal and diseased states.

PMID- 15265885
TI  - Differences in the kinetics, amplitude, and localization of ERK activation in
      anergy and priming revealed at the level of individual primary T cells by laser
      scanning cytometry.
AB  - One of the potential mechanisms of peripheral tolerance is the unresponsiveness
      of T cells to secondary antigenic stimulation as a result of the induction of
      anergy. It has been widely reported that antigenic unresponsiveness may be due to
      uncoupling of MAPK signal transduction pathways. However, such signaling defects
      in anergic T cell populations have been mainly identified using immortalized T
      cell lines or T cell clones, which do not truly represent primary Ag-specific T
      cells. We have therefore attempted to quantify signaling events in murine primary
      Ag-specific T cells on an individual cell basis, using laser-scanning cytometry.
      We show that there are marked differences in the amplitude and cellular
      localization of phosphorylated ERK p42/p44 (ERK1/2) signals when naive, primed
      and anergic T cells are challenged with peptide-pulsed dendritic cells. Primed T
      cells display more rapid kinetics of phosphorylation and activation of ERK than
      naive T cells, whereas anergic T cells display a reduced ability to activate
      ERK1/2 upon challenge. In addition, the low levels of pERK found in anergic T
      cells are distributed diffusely throughout the cell, whereas in primed T cells,
      pERK appears to be targeted to the same regions of the cell as the TCR. These
      data suggest that the different consequences of Ag recognition by T cells are
      associated with distinctive kinetics, amplitude, and localization of MAPK
      signaling.

PMID- 15265884
TI  - Ligand binding to inhibitory killer cell Ig-like receptors induce colocalization
      with Src homology domain 2-containing protein tyrosine phosphatase 1 and
      interruption of ongoing activation signals.
AB  - Interaction of NK cells with target cells leads to formation of an immunological
      synapse (IS) at the contact site. NK cells form two distinctly different IS, the
      inhibitory NK cell IS (NKIS) and the cytolytic NKIS. Cognate ligand binding is
      sufficient to induce clustering of inhibitory killer cell Ig-like receptors (KIR)
      and phosphorylation of both the receptor and the phosphatase Src homology domain
      2-containing protein tyrosine phosphatase 1 (SHP-1). Recruitment and activation
      of SHP-1 by a signaling competent inhibitory receptor are essential early events
      for NK cell inhibition. We have in the present study used three-dimensional
      immunofluorescence microscopy to analyze distribution of inhibitory KIR, SHP-1,
      LFA-1, and lipid rafts within the NKIS during cytolytic and noncytolytic
      interactions. NK clones retrovirally transduced with the inhibitory KIR2DL3 gene
      fused to GFP demonstrate colocalization of KIR2DL3 with SHP-1 in the center of
      early inhibitory NKIS. Ligand binding translocates the receptor to the center of
      the IS where activation signals are accumulating and provides a docking site for
      SHP-1. SHP-1 and rafts cluster in the center of early inhibitory NKIS and late
      cytolytic NKIS, and whereas rafts continue to increase in size in cytolytic
      conjugates, they are rapidly dissolved in inhibitory conjugates. Furthermore,
      rafts are essential only for cytolytic, not for inhibitory, outcome. These
      results indicate that the outcome of NK cell-target cell interactions is dictated
      by early quantitative differences in cumulative activating and inhibitory
      signals.

PMID- 15265886
TI  - Gamma delta T cell regulation of IFN-gamma production by central nervous system
      infiltrating encephalitogenic T cells: correlation with recovery from
      experimental autoimmune encephalomyelitis.
AB  - Interferon-gamma has been shown to be important for the resolution of
      inflammation associated with CNS autoimmunity. Because one of the roles of gamma
      delta T cells is the regulation of inflammation, we asked whether gamma delta T
      cells were able to regulate CNS inflammation using the autoimmune disease mouse
      model experimental autoimmune encephalomyelitis (EAE). We show that the presence
      of gamma delta T cells was needed to promote the production of IFN-gamma by both
      CD4 and CD8 T cells in the CNS before the onset of EAE. This regulation was shown
      to be independent of the ability of gamma delta T cells to produce IFN-gamma, and
      was specific to T cells in the CNS, as no alterations in IFN-gamma production
      were detectable in gamma delta T cell-deficient mice in the spleen and lymph
      nodes of mice with EAE or following immunization. Analysis of TCR gamma delta
      gene usage in the CNS showed that the only TCR delta V gene families present in
      the CNS before EAE onset are from the DV7s6 and DV105s1 gene families. We also
      show that the primary IFN-gamma-producing cells in the CNS are the
      encephalitogenic T cells, and that gamma delta T cell-deficient mice are unable
      to resolve EAE disease symptoms like control mice, thus exhibiting a long-term
      chronic disease course similar to that observed in IFN-gamma-deficient mice.
      These data suggest that CNS resident gamma delta T cells promote the production
      of IFN-gamma by encephalitogenic T cells in the CNS, which is ultimately required
      for the recovery from EAE.

PMID- 15265887
TI  - Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a
      receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine
      production, and chemotaxis.
AB  - The anaphylatoxin C5a is produced following the activation of the complement
      system and is associated with a variety of pathologies, including septic shock
      and adult respiratory distress syndrome, and with immune complex-dependent
      diseases such as rheumatoid arthritis. C5a has been shown to regulate
      inflammatory functions by interacting with its receptor, C5aR, which belong to
      the rhodopsin family of seven-transmembrane GPCRs. However, the intracellular
      signaling pathways triggered by C5aR on immune-effector cells are not well
      understood. In this report we present data showing that, in human monocyte
      derived macrophages, C5aR uses the intracellular signaling molecule sphingosine
      kinase (SPHK)1 to trigger various physiological responses. Our data show that C5a
      rapidly stimulates the generation of sphingosine-1-phosphate, SPHK activity, and
      membrane translocation of SPHK1. Using an antisense oligonucleotide against
      SPHK1, we show that knockdown of SPHK1 abolishes the C5a-triggered intracellular
      Ca(2+) signals, degranulation, cytokine generation, and chemotaxis. Our study
      shows for the first time that SPHK1 not only plays a key role in the generation
      and release of proinflammatory mediators triggered by anaphylatoxins from human
      macrophages but is also involved in the process of immune cell motility, thus
      pointing out SPHK1 as a potential therapeutic target for the treatment of
      inflammatory and autoimmune diseases.

PMID- 15265888
TI  - Regulation of thymus size by competition for stromal niches among early T cell
      progenitors.
AB  - Thymic T cell production is characterized by differentiating waves of non-self
      renewing, bone marrow-derived progenitors. The factors constraining new
      progenitor recruitment, intrathymic precursor expansion, and thymus size remain
      enigmatic, but are believed to be controlled by a feedback loop responding to
      lymphoid cellularity and competition for stromal niches. In this study, we show
      that competition for stromal niches does occur, but is solely limited to cells at
      the early CD4(-)8(-) precursor stages of differentiation. The overall size of the
      organ is determined both by this limitation on early precursor expansion, and by
      a second, cell-intrinsic limit on expansion of progenitor cells transiting to the
      CD4(+)8(+) stage. Together with asymmetric use of marrow-derived progenitors to
      reconstitute the intrathymic pool, these processes facilitate continuous
      generation of new T cells while maintaining a relatively stable organ size.

PMID- 15265889
TI  - I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell
      help, germinal center reactions, and homeostatic expansion.
AB  - Signal transduction from proinflammatory stimuli leading to NF-kappa B-dependent
      gene expression is mediated by the I kappa B kinase 2 (IKK2/IKK beta). Therefore,
      IKK2 has become an important drug target for treatment of inflammatory
      conditions. T cells, whose activation depends to a large extent on the activity
      of NF-kappa B transcription factors, play important roles in inflammation and
      autoimmunity. Ablation of IKK2 specifically in T cells in CD4cre/Ikk2(FL) mice
      allows their survival and activation by polyclonal stimuli in vitro, suggesting
      that IKK2 is dispensable for T cell activation. We report in this study that IKK2
      deficient T cells expand efficiently in response to superantigen administration
      in vivo, but are completely deficient in recall responses, most likely due to
      inefficient priming. IKK2-deficient T cells provide suboptimal B cell help and
      fail to support germinal center reactions. Finally, IKK2 is essential for
      homeostatic expansion of naive T cells, reflected by the inability of IKK2
      deficient T cells to induce colitis in lymphopenic hosts.

PMID- 15265890
TI  - Critical roles of CXC chemokine ligand 16/scavenger receptor that binds
      phosphatidylserine and oxidized lipoprotein in the pathogenesis of both acute and
      adoptive transfer experimental autoimmune encephalomyelitis.
AB  - The scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR
      PSOX)/CXCL16 is a chemokine expressed on macrophages and dendritic cells, while
      its receptor expresses on T and NK T cells. We investigated the role of SR
      PSOX/CXCL16 on acute and adoptive experimental autoimmune encephalomyelitis
      (EAE), which is Th1-polarized T cell-mediated autoimmune disease of the CNS.
      Administration of mAb against SR-PSOX/CXCL16 around the primary immunization
      decreased disease incidence of acute EAE with associated reduced infiltration of
      mononuclear cells into the CNS. Its administration was also shown to inhibit
      elevation of serum IFN-gamma level at primary immune response, as well as
      subsequent generation of Ag-specific T cells. In adoptive transfer EAE, treatment
      of recipient mice with anti-SR-PSOX/CXCL16 mAb also induced not only decreased
      clinical disease incidence, but also diminished traffic of mononuclear cells into
      the CNS. In addition, histopathological analyses showed that clinical development
      of EAE correlates well with expression of SR-PSOX/CXCL16 in the CNS. All the
      results show that SR-PSOX/CXCL16 plays important roles in EAE by supporting
      generation of Ag-specific T cells, as well as recruitment of inflammatory
      mononuclear cells into the CNS.

PMID- 15265891
TI  - Lipid raft-associated GTPase signaling controls morphology and CD8+ T cell
      stimulatory capacity of human dendritic cells.
AB  - Their eponymous morphology and unique ability to activate naive T cells are
      hallmark features of dendritic cells (DCs). Specific properties of the actin
      cytoskeleton may define both characteristics. In search for regulators that
      coordinate DC phenotype and function, we observed strongly increased expression
      of the actin-remodeling GTPases Cdc42 and Rac1 during DC development from human
      stem cells. Cdc42 and Rac1 are constitutively active in immature DCs, and their
      activity is further up-regulated by maturational stimuli such as LPS or CD40L.
      Activation of Rac1 is associated with its rapid recruitment into lipid rafts.
      Cdc42 is not recruited into rafts, but readily activated by raft-associated
      moieties. The functional interplay of rafts, GTPases, and cortical actin is
      further shown by GTPase activation and actin remodeling after pharmacological
      disruption of lipid rafts and by the loss of the actin-based DC morphology by
      transfection of dominant-negative Cdc42 and Rac1. Both Cdc42 and Rac1 also
      control the transport of essential immunostimulatory molecules to the DC surface.
      Transfection with dominant-negative GTPases led to reduced surface expression of
      MHC class I and CD86. Consecutively, DCs display a reduced stimulatory capacity
      for CD8(+) T cells, whereas MHC class II-dependent stimulation of CD4(+) T cells
      remains unperturbed. We conclude that Cdc42 and Rac1 signaling controls DC
      morphology and conditions DCs for efficient CD8(+) T cell stimulation.

PMID- 15265892
TI  - In vivo generated Th1 cells can migrate to B cell follicles to support B cell
      responses.
AB  - The description of Th1 and Th2 T cell subsets rationalized the inverse
      correlation between humoral and cell-mediated immunity. Although Th1 cells were
      described to support cell-mediated immune responses, their role in supporting
      certain B cell responses was firmly established. However, there is now a
      prevailing preconception that provision of B cell help is entirely the domain of
      Th2 cells and that Th1 cells lack this capacity. Previous studies demonstrated
      that immunization using aluminum hydroxide adjuvants induces Ag-specific Th2
      responses, whereas incorporation of IL-12 with aluminum hydroxide produces a Th1
      inducing adjuvant. By immunizing TCR transgenic recipient mice in this fashion,
      we have generated Ag-specific, traceable Th1 and Th2 cells in vivo and assessed
      their follicular migration and ability to support B cell responses. In this study
      we have shown that in vivo polarized Th1 and Th2 cells clonally expand to similar
      levels and migrate into B cell follicles in which they support B cell responses
      to a similar degree. Critically, we present direct evidence that in vivo
      polarized, IFN-gamma secreting Th1 cells migrate into B cell follicles where they
      can interact with Ag-specific B cells.

PMID- 15265893
TI  - CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid
      dendritic cells in rhesus macaques to augment the activation of IFN-gamma
      secreting simian immunodeficiency virus-specific T cells.
AB  - There are two principle subsets of dendritic cells (DCs); CD11c(+)CD123(-)
      myeloid DCs (MDCs) and CD11c(-)CD123(+) plasmacytoid DCs (PDCs). DC activation
      via TNF-TNFRs (e.g., CD40L) and TLRs (e.g., immunostimulatory
      oligodeoxyribonucleotides (ISS-ODNs)) is crucial for maximal stimulation of
      innate and adaptive immunity. Macaque DC biology is being studied to improve HIV
      vaccines using the SIV macaque model. Using lineage (Lin) markers to exclude non
      DCs, Lin(-)HLA-DR(+)CD11c(+)CD123(-) MDCs and Lin(-)HLA-DR(+)CD11c(-)CD123(+)
      PDCs were identified in the blood of uninfected macaques and healthy macaques
      infected with SIV or simian-human immunodeficiency virus. Overnight culture of DC
      enriched Lin-depleted cells increased CD80 and CD86 expression. IL-12 production
      and CD80/CD86 expression by MDC/PDC mixtures was further enhanced by CD40L and
      ISS-ODN treatment. A CpG-B ISS-ODN increased CD80/CD86 expression by PDCs, but
      resulted in little IFN-alpha secretion unless IL-3 was added. In contrast, a CpG
      C ISS-ODN and aldrithiol-2-inactivated (AT-2) SIV induced considerable PDC
      activation and IFN-alpha release without needing exogenous IL-3. The CpG-C ISS
      ODN also stimulated IL-12 release (unlike AT-2 SIV) and augmented DC
      immunostimulatory activity, increasing SIV-specific T cell IFN-gamma production
      induced by AT-2 SIV-presenting MDC/PDC-enriched mixtures. These data highlight
      the functional capacities of MDCs and PDCs in naive as well as healthy, infected
      macaques, revealing a promising CpG-C ISS-ODN-driven DC activation strategy that
      boosts immune function to augment preventative and therapeutic vaccine efficacy.

PMID- 15265894
TI  - Differential roles for Wiskott-Aldrich syndrome protein in immune synapse
      formation and IL-2 production.
AB  - Wiskott-Aldrich syndrome protein (WASP)-deficient T cells exhibit defects in IL-2
      production that are widely believed to stem from primary defects in actin
      remodeling and immune synapse formation. Surprisingly, however, we find that WASP
      deficient T cells responding to Ag-specific APCs polymerize actin and organize
      talin and PKC theta normally, forming an immune synapse that is stable for at
      least 3 h. At low doses of peptide, WASP-deficient T cells show less efficient
      talin and PKC theta polarization. Thus, although WASP may facilitate immune
      synapse formation at low peptide concentrations, WASP is not required for this
      process. Defects in IL-2 production are observed even under conditions in which
      immune synapse formation proceeds normally, suggesting that the role of WASP in
      regulating IL-2 production is independent of its role in immune synapse
      formation.

PMID- 15265895
TI  - IFN-alpha subtypes differentially affect human T cell motility.
AB  - The type I IFN family includes 14 closely related antiviral cytokines that are
      produced in response to viral infections. They bind to a common receptor, and
      have qualitatively similar biological activities. The physiological relevance of
      this redundancy is still unclear. In this study, we analyzed and compared the
      effects of two potent antiviral type I IFNs, IFN-alpha 2 and IFN-alpha 8, on the
      motility of various populations of human T lymphocytes in vitro. In this study,
      we show that IFN-alpha 2 induces chemokinesis of both CD4(+) and CD8(+) T cells
      at various stages of differentiation, and induces functional changes that result
      in enhanced T cell motility, including up-regulation of the integrins LFA-1 and
      VLA-4, and subsequently, increased ICAM-1- and fibronectin-dependent migration.
      In contrast, IFN-alpha 8 did not affect T cell motility, despite having similar
      antiviral properties and similar effects on the induction of the antiviral
      protein MxA. However, transcription of other IFN-stimulated genes showed that
      transcription of these genes is selectively activated by IFN-alpha 2, but not IFN
      alpha 8, in T cells. Finally, while the antiviral activity of the two subtypes is
      inhibited by Abs against the two subunits of the IFN-alpha receptor, the
      chemokinetic effect of IFN-alpha 2 is selectively blocked by Abs against the A1
      receptor subunit. These observations are consistent with the possibility that
      subtype-specific intracellular signaling pathways are activated by type I IFNs in
      T lymphocytes.

PMID- 15265896
TI  - T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to
      subsequent activation.
AB  - Paradoxically, while peripheral self-tolerance exists for constitutively
      presented somatic self Ag, self-peptide recognized in the context of MHC class II
      has been shown to sensitize T cells for subsequent activation. We have shown that
      MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the
      presence of an NF-kappa B inhibitor, and which constitutively populate peripheral
      tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance.
      In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC),
      generated in the presence of an NF-kappa B inhibitor, signal phosphorylation of
      TCR zeta, but little proliferation or IFN-gamma in vitro. Proliferation is
      arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T
      cells are neither anergic nor regulatory, but are sensitized for subsequent IFN
      gamma production. The data indicate that signaling through NF-kappa B determines
      the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappa B(
      )CD40(-)class II(+) DC may either tolerize or sensitize T cells. Thus, while
      CD40(-) DC appear to "prime" or prepare T cells, the data imply that signals
      derived from other cells drive the generation either of Ag-specific regulatory or
      effector cells in vivo.

PMID- 15265897
TI  - Natural, proteolytic release of a soluble form of human IL-15 receptor alpha
      chain that behaves as a specific, high affinity IL-15 antagonist.
AB  - IL-15 and IL-2 are two structurally and functionally related cytokines whose high
      affinity receptors share the IL-2R beta-chain and gamma-chain in association with
      IL-15R alpha-chain (IL-15R alpha) or IL-2R alpha-chain, respectively. Whereas IL
      2 action seems restricted to the adaptative T cells, IL-15 appears to be crucial
      for the function of the innate immune responses, and the pleiotropic expression
      of IL-15 and IL-15R alpha hints at a much broader role for the IL-15 system in
      multiple cell types and tissues. In this report, using a highly sensitive
      radioimmunoassay, we show the existence of a soluble form of human IL-15R alpha
      (sIL-15R alpha) that arises from proteolytic shedding of the membrane-anchored
      receptor. This soluble receptor is spontaneously released from IL-15R alpha
      expressing human cell lines as well as from IL-15R alpha transfected COS-7 cells.
      This release is strongly induced by PMA and ionomycin, and to a lesser extent by
      IL-1 beta and TNF-alpha. The size of sIL-15R alpha (42 kDa), together with the
      analysis of deletion mutants in the ectodomain of IL-15R alpha, indicates the
      existence of cleavage sites that are proximal to the plasma membrane. Whereas
      shedding induced by PMA was abrogated by the synthetic matrix metalloproteinases
      inhibitor GM6001, the spontaneous shedding was not, indicating the occurrence of
      at least two distinct proteolytic mechanisms. The sIL-15R alpha displayed high
      affinity for IL-15 and behaved as a potent and specific inhibitor of IL-15
      binding to the membrane receptor, and of IL-15-induced cell proliferation (IC(50)
      in the range from 3 to 20 pM). These results suggest that IL-15R alpha shedding
      may play important immunoregulatory functions.

PMID- 15265898
TI  - Cross-reactive TCR responses to self antigens presented by different MHC class II
      molecules.
AB  - Autoreactive T cells represent a natural repertoire of T cells in both diseased
      patients and healthy individuals. The mechanisms regulating the function of these
      autoreactive T cells are still unknown. Ob1A12 is a myelin basic protein (MBP)
      reactive Th cell clone derived from a patient with relapsing-remitting multiple
      sclerosis. Mice transgenic for this human TCR and DRA and DRB1*1501 chains
      develop spontaneous experimental autoimmune encephalomyelitis. The reactivity of
      Ob1A12 is reported to be restricted to recognition of MBP peptide 85-99 in the
      context of DRB1*1501. DRA/DRB1*1501 and the patient's other restriction element,
      DRA/DRB1*0401, differ significantly in their amino acid sequences. In this study
      we describe an altered peptide ligand derived from MBP(85-99) with a single amino
      acid substitution at position 88 (Val to Lys; 88V-->K), that could stimulate the
      Ob1A12.TCR in the context of both DRA/DRB1*1501 and DRA/DRB1*0401. Analysis of a
      panel of transfected T cell hybridomas expressing Ob1A12.TCR and CD4 indicated
      that Ob1A12.TCR cross-reactivity in the context of DRA/DRB1*0401 is critically
      dependent on the presence of the CD4 coreceptor. Furthermore, we found that
      activation of Ob1A12.TCR with MBP altered peptide ligand 85-99 88V-->K presented
      by DRB1*1501 or DRB1*0401 resulted in significant differences in TCR zeta
      phosphorylation. Our data indicate that injection of altered peptide ligand into
      patients heterozygous for MHC class II molecules may result in unexpected cross
      reactivities, leading to activation of autoreactive T cells.

PMID- 15265899
TI  - HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models
      of spondyloarthritis and are ligands for paired Ig-like receptors.
AB  - HLA-B27 transgenic rats and strains of HLA-B27-transgenic beta(2)-microglobulin
      (beta(2)m)-deficient mice develop a multisystem inflammatory disease affecting
      the joints, skin, and bowel with strong similarity to human spondyloarthritis. We
      show that HLA-B27 transgenic mice and rats express HC10-reactive, beta(2)m-free
      HLA-B27 homodimers (B27(2)) and multimers, both intracellularly and at the cell
      surface of leukocytes, including rat dendritic cells. Fluorescent-labeled
      tetrameric complexes of HLA-B27 homodimers (B27(2) tetramers) bind to populations
      of lymphocytes, monocytes, and dendritic cells. The murine (and probably rat)
      paired Ig-like receptors (PIRs) are ligands for B27(2). Thus, B27(2) tetramers
      stain RBL cells transfected with murine activating PIR-A4 and inhibitory PIR-B
      receptors. Murine PIR-A and -B can be immunoprecipitated from the RAW264.7
      macrophage cell line, and murine PIR-A can be immunoprecipitated from the J774.A1
      line using B27(2). B27(2) tetramer staining corresponds to the distribution of
      PIR expression on lymphoid and myeloid cells and on murine macrophage cell lines.
      B27(2) can induce TNF-alpha release from the J774.A1 macrophage cell line. The
      binding of B27(2) to PIR is inhibited by HC10, an mAb that ameliorates arthritis
      in HLA-B27(+) beta(2)m(-/-) mice. The expression and PIR recognition of B27(2)
      could explain the pathogenesis of rodent spondyloarthritis.

PMID- 15265900
TI  - The Gads (GrpL) adaptor protein regulates T cell homeostasis.
AB  - Little is known about the role of the Gads (GrpL) adaptor protein in mature T
      cell populations. In this study we show that the effects of Gads deficiency on
      murine CD4(+) and CD8(+) T cells are markedly different. Gads(-/-) CD4(+) T cells
      were markedly deficient in the spleen and had an activated phenotype and a rapid
      turnover rate. When transferred into a wild-type host, Gads(-/-) CD4(+) T cells
      continued to proliferate at a higher rate than wild-type CD4(+) T cells,
      demonstrating a defect in homeostatic proliferation. Gads(-/-) CD8(+) T cells had
      a memory-like phenotype, produced IFN-gamma in response to ex vivo stimulation,
      and underwent normal homeostatic proliferation in wild-type hosts. Gads(-/-) T
      cells had defective TCR-mediated calcium responses, but had normal activation of
      ERK. Gads(-/-) CD4(+) T cells, but not CD8(+) T cells, had a severe block of TCR
      mediated proliferation and a high rate of spontaneous cell death and were highly
      susceptible to CD95-induced apoptosis. This suggests that the rapid turnover of
      Gads(-/-) CD4(+) T cells is due to a defect in cell survival. The intracellular
      signaling pathways that regulate homeostasis in CD4(+) and CD8(+) T cells are
      clearly different, and the Gads adaptor protein is critical for homeostasis of
      CD4(+) T cells.

PMID- 15265901
TI  - MUC1/sec-expressing tumors are rejected in vivo by a T cell-dependent mechanism
      and secrete high levels of CCL2.
AB  - MUC1/sec is a secreted form of the glycoprotein mucin 1 (MUC1). To characterize
      the role that MUC1 and MUC1/sec have in tumor progression, these genes were
      expressed in DA-3 mammary tumor cells. DA-3 cells and DA-3 cells expressing the
      transmembrane MUC1 gene (DA-3/TM) grow with similar kinetics in BALB/c mice.
      Surprisingly, DA-3 cells expressing and secreting MUC1/sec (DA-3/sec) fail to
      form tumors in vivo. The mechanism of rejection was evaluated using mice
      deficient in constituents of the immune system. All mice lacking IFN-gamma, NK,
      NKT, or macrophages formed DA-3/sec tumors that regressed shortly after
      implantation. However, progressively growing DA-3/sec tumors developed in mice
      devoid of T lymphocytes. The importance of T lymphocytes in the rejection of DA
      3/sec tumors was further supported by detection of DA-3-specific CTL in mice
      challenged with the DA-3/sec tumor. Recruitment of appropriate APC and effector
      cells is an important first step in the tumor clearance. Indeed, DA-3/sec cells
      or cell supernatants recruited 3-4 times as many macrophages as DA-3/TM cells in
      vivo, suggesting that a secreted chemotactic product is produced from DA-3/sec
      cells. RNA and protein analysis of DA-3/sec cells revealed that several genes are
      up-regulated by MUC1/sec expression, including MCP-1 (CCL-2). These results
      suggest DA-3/sec cells are capable of recruiting immune cells, and that rejection
      of DA-3/sec tumors, although aided by cells of the innate immune response, is
      ultimately due to T cell-mediated events.

PMID- 15265902
TI  - A synthetic peptide homologous to functional domain of human IL-10 down-regulates
      expression of MHC class I and Transporter associated with Antigen Processing 1/2
      in human melanoma cells.
AB  - Tumor cells treated with IL-10 were shown to have decreased, but peptide
      inducible expression of MHC class I, decreased sensitivity to MHC class I
      restricted CTL, and increased NK sensitivity. These findings could be explained,
      at least partially, by a down-regulation of TAP1/TAP2 expression. In this study,
      IT9302, a nanomeric peptide (AYMTMKIRN), homologous to the C-terminal of the
      human IL-10 sequence, was demonstrated to mimic these previously described IL-10
      effects on MHC class I-related molecules and functions. We observed a dose
      dependent down-regulation of MHC class I at the cell surface of melanoma cells
      after 24-h treatment with IT9302. The IL-10 homologue peptide also caused a dose
      dependent inhibition of the IFN-gamma-mediated surface induction of MHC class I
      in a melanoma cell line. We demonstrated, using Western blot and flow cytometry,
      that IT9302 inhibits the expression of TAP1 and TAP2 proteins, but not MHC class
      I H chain or low molecular protein molecules. Finally, peptide-treated melanoma
      cells were shown to be more sensitive to lysis by NK cells in a dose-dependent
      way. Taken together, these results demonstrate that a small synthetic peptide
      derived from IL-10 can mimic the Ag presentation-related effects mediated by this
      cytokine in human melanomas and increase tumor sensitivity to NK cells, which can
      be relevant in the designing of future strategies for cancer immune therapy.

PMID- 15265903
TI  - The rate of the CD8-dependent initial reduction in tumor volume is not limited by
      contact-dependent perforin, Fas ligand, or TNF-mediated cytolysis.
AB  - Established EG7 tumors expressing OVA and growing at an intradermal site become
      rapidly reduced in size following adoptive therapy with in vitro-generated type I
      CD8 T cell (Tc1) effectors generated from naive CD8 T cells from transgenic TCR
      OVA-specific mice. Tc1 effectors kill EG7 target cells in vitro by a perforin
      dependent mechanism. However, we show that there is no quantitative diminution of
      the initial phase of antitumor activity in vivo, whether the Tc1 effectors are
      derived from perforin-, Fas ligand-, or TNF-deficient transgenic TCR mice or
      whether the recipients are perforin deficient. Tumors are also equally well
      controlled whether the Tc1 effectors come from mice deficient in perforin plus
      Fas ligand or perforin plus TNF. Control of tumor growth is diminished when Tc1
      effectors generated from IFN-gamma-deficient mice are used. We conclude that
      control of tumor growth is not in any way affected by loss of contact-mediated
      lytic mechanisms, and conclude that the CD8 effectors must act by recruiting host
      effector mechanisms to control tumor growth.

PMID- 15265904
TI  - Endogenous nitric oxide protects against T cell-dependent lethality during graft
      versus-host disease and idiopathic pneumonia syndrome.
AB  - The pathogenesis of idiopathic pneumonia syndrome (IPS), a noninfectious
      pulmonary complication of allogeneic bone marrow transplantation (BMT), has not
      been fully elucidated. However, several contributing factors have been proposed,
      including lung injury caused by reactive oxygen and nitrogen intermediates during
      preconditioning and development of graft-vs-host disease (GVHD). Studies on the
      role of reactive oxygen and nitrogen intermediates in IPS have yielded
      conflicting results. We have described a murine model of IPS, in which the onset
      of lung inflammation was delayed by several weeks relative to GVHD. This study
      evaluated whether the delay in onset of IPS was due to slow turnover of NO
      producing, immunosuppressive alveolar macrophages (AM) following BMT. The results
      indicated that AM were immunosuppressive due to synthesis of NO. However, NO
      production and immunosuppressive activity by AM did not decline after BMT, but
      rather remained elevated throughout the 12-wk development of GVHD and IPS. In a
      14-day model of IPS, continuous inhibition of NO with aminoguanidine (AG) reduced
      signs of IPS/GVHD, but also led to higher mortality. When AG treatment was
      initiated after onset of IPS/GVHD, rapid mortality occurred that depended on the
      severity of IPS/GVHD. AG-enhanced mortality was not due to inhibition of marrow
      engraftment, elevated serum TNF-alpha, liver injury, or hypertensive responses.
      In contrast, T cells were involved, because depletion of CD4(+) lymphocytes 24 h
      before AG treatment prevented mortality. Thus, NO production following allogeneic
      BMT affords a protective effect that helps down-regulate injury caused by T cells
      during GVHD and IPS.

PMID- 15265905
TI  - Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide
      naturally formed by gastrointestinal digestion.
AB  - Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T
      cell responses to ingested wheat gluten proteins. A peptide fragment of 33
      residues (alpha(2)-gliadin 56-88) produced by normal gastrointestinal proteolysis
      contains six partly overlapping copies of three T cell epitopes and is a
      remarkably potent T cell stimulator after deamidation by tissue transglutaminase
      (TG2). This 33-mer is rich in proline residues and adopts the type II polyproline
      helical conformation in solution. In this study we report that after deamidation,
      the 33-mer bound with higher affinity to DQ2 compared with other monovalent
      peptides harboring gliadin epitopes. We found that the TG2-treated 33-mer was
      presented equally effectively by live and glutaraldehyde-fixed, EBV-transformed B
      cells. The TG2-treated 33-mer was also effectively presented by glutaraldehyde
      fixed dendritic cells, albeit live dendritic cells were the most effective APCs.
      A strikingly increased T cell stimulatory potency of the 33-mer compared with a
      12-mer peptide was also seen with fixed APCs. The 33-mer showed binding maximum
      to DQ2 at pH 6.3, higher than maxima found for other high affinity DQ2 binders.
      The 33-mer is thus a potent T cell stimulator that does not require further
      processing within APC for T cell presentation and that binds to DQ2 with a pH
      profile that promotes extracellular binding.

PMID- 15265906
TI  - Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes
      the T cell repertoire against this circulating self antigen in wild-type mice.
AB  - We have studied T cell tolerance to defined determinants within ML-M using wild
      type (WT; ML-M(+/+)) and LysMcre (ML-M(-/-)) C3H (H-2(k)) mice to determine the
      relative contribution of ML-M-derived epitopes vs those from other self Ags in
      selection of the ML-M-specific T cell repertoire. ML-M was totally nonimmunogenic
      in WT mice, but was rendered immunogenic in LysMcre mice. Most of the response to
      ML-M in LysMcre mice was directed to the immunodominant determinant region 105
      119. This determinant is spontaneously displayed (without adding exogenous ML-M)
      by macrophages of WT, but not LysMcre, mice and is stimulatory for peptide 105
      119 (p105-119)-primed T cells. Moreover, neonatal tolerization of LysMcre mice
      with p105-119 or ML-M abrogated the T cell response to subsequent challenge with
      ML-M or p105-119. Furthermore, p95-109 and p110-125 of ML-M were immunogenic in
      LysMcre mice, but not in WT mice, thereby representing subdominant, tolerance
      inducing epitopes of ML-M. As expected, the T cell repertoire to cryptic ML
      determinants in WT mice was also intact in LysMcre mice. Furthermore, the pattern
      of response to the related homologue of ML-M, hen eggwhite lysozyme, was similar
      in these two groups of mice. Thus, several codominant T cell determinants within
      ML-M contribute significantly to tolerance induction, and the anti-cryptic T cell
      repertoire to ML-M was positively selected on non-ML-M self ligands. These
      results reveal that the induction of self tolerance to a multideterminant protein
      follows the quantitative hierarchy of self-determinant expression and are of
      relevance in understanding the pathogenesis of autoimmunity.

PMID- 15265907
TI  - Alpha-fetoprotein impairs APC function and induces their apoptosis.
AB  - alpha-Fetoprotein (AFP) is a tumor-associated Ag, and its serum level is elevated
      in patients with hepatocellular carcinoma (HCC). In vitro, AFP induces functional
      impairment of dendritic cells (DCs). This was demonstrated by the down-regulation
      of CD40 and CD86 molecules and the impairment of allostimulatory function. Also,
      AFP was found to induce significant apoptosis of DCs, and AFP-treated DCs
      produced low levels of IL-12 and TNF-alpha, a cytokine pattern that could hamper
      an efficient antitumor immune response. Ex vivo, APCs of patients with HCC and
      high levels of AFP produced lower levels of TNF-alpha than that of healthy
      individuals. In conclusion, these results illustrate that AFP induces dysfunction
      and apoptosis of APCs, thereby offering a mechanism by which HCC escapes
      immunological control.

PMID- 15265908
TI  - ICOS expression by activated human Th cells is enhanced by IL-12 and IL-23:
      increased ICOS expression enhances the effector function of both Th1 and Th2
      cells.
AB  - Previous mouse studies have shown that IL-4 increases the expression of ICOS on
      activated Th cells, resulting in enhanced ICOS expression on Th2 cells. In this
      study, we show that ICOS expression on human Th cells is not increased by IL-4,
      but by IL-12 and by IL-23 instead. Consequently, ICOS expression during IL-12
      driven Th1 cell polarization was transiently increased compared with the levels
      on Th0 cells and IL-4-driven Th2 cells. Addition of IL-12 and/or IL-23 during
      restimulation increased ICOS expression to the same extent on pre-established
      Th1, Th2, and Th0 cells, indicating that ICOS levels are not stably imposed by
      prior polarization. In contrast to the findings in the mouse, IL-4 significantly
      suppressed the ICOS-enhancing effects of IL-12 and IL-23. The functional
      consequence of variable ICOS levels was shown in coculture experiments with cells
      expressing the ICOS-ligand B7-related protein 1 (either transfected Chinese
      hamster ovary cells or autologous dendritic cells). Ligation of ICOS on 2-day
      preactivated effector cells increased their cytokine production to an extent
      proportional to their ICOS expression levels. As the ICOS-enhancing potentials of
      IL-12 and IL-23 were maintained for several days after stimulation, both on Th1
      and Th2 cells, we propose the concept that local regulation of ICOS expression on
      activated Th cells by IL-12 and/or IL-23 may provide a powerful means to amplify
      effector T cell responses in peripheral tissues, independently of the polarized
      state of the Th cells.

PMID- 15265909
TI  - Direct measurement of T cell subset kinetics in vivo in elderly men and women.
AB  - The age-associated decline in immunocompetence is paralleled by changes in the
      proportions of PBL subpopulations. In turn, the size and composition of the
      peripheral lymphocyte pool is determined by input from the thymus and bone marrow
      and by the balance of proliferation and death in each lymphocyte subpopulation.
      We compared the kinetics of lymphocyte subtypes in young (seven of eight CMV
      seronegative) and healthy elderly human subjects (six of seven CMV seropositive),
      using deuterated glucose DNA labeling in vivo to measure rates of T cell
      proliferation and disappearance. For CD45RO(+) cells of both CD4(+) and CD8(+)
      subtypes and for CD4(+)CD45RA(+) cells the kinetics of proliferation and
      disappearance were remarkably similar between elderly and young subjects. In the
      young, the kinetics of CD8(+)CD45RA(+) cells with a naive phenotype resembled
      those of CD4(+)CD45RA(+) cells. However, CD8(+)CD45RA(+) T cells from the elderly
      exhibited a predominantly primed phenotype, and for this subset, although the
      proliferation rate was similar to that of other CD45RA(+) cells, the
      disappearance rate of labeled cells was greatly decreased compared with that of
      all other T cell subsets. Our data provide a direct demonstration that there are
      no substantial changes in in vivo kinetics for most T cell populations in healthy
      elderly compared with young subjects. However, primed CD8(+)CD45RA(+) cells show
      unusual kinetic properties, indicating the persistence of these cells in the
      blood and dissociation of proliferation from disappearance.

PMID- 15265910
TI  - T cell immunity to type II collagen in the biobreeding rat: the identification
      and characterization of RT1u-restricted T cell epitopes on alpha 1(II).
AB  - Susceptibility to experimental collagen-induced arthritis in rodents is dependent
      on MHC class II elements to bind peptides from the type II collagen (CII)
      molecule. Although a substantial body of data has been reported in mice defining
      these peptide Ags, little has been reported in rats. In this study, we
      investigate the locations and sequences of CII peptides, which are bound by
      RT1(u) molecules, expressed by diabetic-resistant, arthritis-susceptible
      Biobreeding rats, and, in turn, stimulate CII-specific T cells. By using
      overlapping and substituted peptide homologues of CII, we have identified and
      characterized an immunodominant and five subdominant epitopes on CII, which
      stimulate RT1(u)-restricted T cell proliferation. The immunodominant epitope, CII
      (186-192), contains a QGPRG core sequence, which was found in a subdominant
      epitope CII (906-916). Similar sequences containing single conservative
      substitutions were identified in three other epitopes. One, CII (263-272),
      contained a conservatively substituted R-->K substitution, whereas CII (880-889)
      and CII (906-916) contained nonconservative substitutions, i.e., P-->D and R-->M,
      respectively. Homologue peptides containing these sequences stimulated T cell
      proliferative responses, although less intensely than peptides containing CII
      (186-192). Substituting QGR residues in the QGPRG core with alanine, isoleucine,
      or proline reduced proliferation, as did substituting flanking E and G residues
      at the N terminus and E at the C terminus. Collectively, these data indicate that
      RT1(u)-restricted immunodominant and several subdominant epitopes on CII often
      share a QGPRG-like motif, with conservative substitutions present at either P or
      R positions. This motif is similar to one recognized by collagen-induced
      arthritis-susceptible HLA-DR1- and HLA-DR4-transgenic mice.

PMID- 15265911
TI  - Cyclic adenosine 5'-monophosphate response element binding protein plays a
      central role in mediating proliferation and differentiation downstream of the pre
      TCR complex in developing thymocytes.
AB  - The roles played by specific transcription factors during the regulation of early
      T cell development remain largely undefined. Several key genes induced during the
      primary checkpoint of T cell development, beta-selection, contain cAMP response
      element sites within their enhancer-promoter region that are regulated by CREB
      activation. In this study, we show that CREB is constitutively phosphorylated in
      the thymus, but not the spleen. We also show that CREB is activated downstream of
      the pre-TCR complex, and that the induction of CREB activity is regulated by
      protein kinase C alpha- and ERK-MAPK-mediated signals. We addressed the
      importance of this activation by expressing a naturally occurring inhibitor of
      CREB, inducible cAMP early repressor in wild-type fetal liver-derived lymphoid
      progenitor cells, and assessed their developmental potential. Fetal thymic organ
      cultures reconstituted with cells constitutively expressing inducible cAMP early
      repressor displayed a delay in generating CD4(+)CD8(+) thymocytes and a decrease
      in cellularity compared with control fetal thymic organ cultures. Taken together,
      our studies establish that CREB plays a central role in relaying proliferation
      and differentiation signals from the pre-TCR complex into the nucleus in
      developing thymocytes.

PMID- 15265912
TI  - Inactivation of c-Cbl or Cbl-b differentially affects signaling from the high
      affinity IgE receptor.
AB  - The Cbl family of proteins negatively regulate signaling from tyrosine kinase
      coupled receptors. Among the three members of this family, only c-Cbl and Cbl-b
      are expressed in hemopoietic cells. To examine the role of c-Cbl and Cbl-b in Fc
      epsilon RI signaling, mast cell cultures from wild-type, c-Cbl(-/-), and Cbl-b(-/
      ) mice were generated. Cell growth rates and cell surface expression of Fc
      epsilon RI were similar in the different cell populations. Compared with control
      cells, Cbl-b inactivation resulted in increases in Fc epsilon RI-induced Ca(2+)
      response and histamine release. Fc epsilon RI-induced tyrosine phosphorylation of
      total cellular proteins, Syk, and phospholipase C-gamma was also enhanced by Cbl
      b deficiency, whereas receptor-initiated phosphorylation of Vav, JNK, and p38
      kinases was not changed in these cells. In contrast to Cbl-b, c-Cbl deficiency
      had no detectable effect on Fc epsilon RI-induced histamine release or on the
      phosphorylation of total cellular proteins or Syk. The absence of c-Cbl increased
      the phosphorylation of ERK after receptor stimulation, but resulted in slightly
      reduced p38 phosphorylation and Ca(2+) response. These results suggest that Cbl-b
      and c-Cbl have divergent effects on Fc epsilon RI signal transduction and that
      Cbl-b, but not c-Cbl, functions as a negative regulator of Fc epsilon RI-induced
      degranulation.

PMID- 15265913
TI  - MHC class I-independent recognition of NK-activating receptor KIR2DS4.
AB  - Natural killer cells are capable of killing tumor and virus-infected cells. This
      killing is mediated primarily via the natural cytotoxicity receptors, including
      NKp46, NKp44, NKp30, and by the NKG2D receptor. Killer cell Ig-like receptors
      (KIRs) are mainly involved in inhibiting NK killing (inhibitory KIRs) via
      interaction with MHC class I molecules. Some KIRs, however, have been found to
      enhance NK killing when interacting with MHC class I molecules (activating KIRs).
      We have previously demonstrated that KIR2DS4, an activating KIR, recognizes the
      HLA-Cw4 protein. The interaction observed was weak and highly restricted to HLA
      Cw4 only. These findings prompted us to check whether KIR2DS4 might have
      additional ligand(s). In this study, we show that KIR2DS4 is able to also
      interact with a non-class I MHC protein expressed on melanoma cell lines and on a
      primary melanoma. This interaction is shown to be both specific and functional.
      Importantly, site-directed mutagenesis analysis reveals that the amino acid
      residues involved in the recognition of this novel ligand are different from
      those interacting with HLA-Cw4. These results may shed new light on the function
      of activating KIRs and their relevance in NK biology.

PMID- 15265914
TI  - Characterization of distinct conventional and plasmacytoid dendritic cell
      committed precursors in murine bone marrow.
AB  - The developmental pathways and differentiation relationship of dendritic cell
      (DC) subsets remain unclear. We report that murine CD11c(+)MHC II(-) bone marrow
      cells, which are immediate DC precursors of CD8 alpha(+), CD8 alpha(-), and
      B220(+) DC in vivo, can be separated into B220(+) and B220(-) DC precursor
      subpopulations. Purified B220(-) DC precursors expand, and generate exclusively
      mature CD11c(+)CD11b(+)B220(-) DC in vitro and after adoptive transfer. B220(+)
      DC precursors, which resemble plasmacytoid pre-DC, have a lower proliferative
      potential than B220(-) DC precursors and generate both CD11b(-) B220(+) and
      CD11b(+)B220(-) DC populations. Both DC precursor populations can give rise to
      CD8 alpha(+) and CD8 alpha(-) DC subtypes. Our findings indicate that CD11c(+)MHC
      II(-)B220(+) and CD11c(+)MHC II(-)B220(-) bone marrow cells are distinct DC
      lineage-restricted precursors.

PMID- 15265915
TI  - Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset
      after recovery of primary cytomegalovirus infection.
AB  - Cytotoxic CD4(+)CD28(-) T cells form a rare subset in human peripheral blood. The
      presence of CD4(+)CD28(-) cells has been associated with chronic viral
      infections, but how these particular cells are generated is unknown. In this
      study, we show that in primary CMV infections, CD4(+)CD28(-) T cells emerge just
      after cessation of the viral load, indicating that infection with CMV triggers
      the formation of CD4(+)CD28(-) T cells. In line with this, we found these cells
      only in CMV-infected persons. CD4(+)CD28(-) cells had an Ag-primed phenotype and
      expressed the cytolytic molecules granzyme B and perforin. Importantly,
      CD4(+)CD28(-) cells were to a large extent CMV-specific because proliferation was
      only induced by CMV-Ag, but not by recall Ags such as purified protein derivative
      or tetanus toxoid. CD4(+)CD28(-) cells only produced IFN-gamma after stimulation
      with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to
      varicella-zoster virus and purified protein derivative. Thus, CD4(+)CD28(-) T
      cells emerge as a consequence of CMV infection.

PMID- 15265916
TI  - Transcription-dependent somatic hypermutation occurs at similar levels on
      functional and nonfunctional rearranged IgH alleles.
AB  - Allelic exclusion of IgH chain expression is stringently established before or
      during early B cell maturation. It likely relies both on cellular mechanisms,
      selecting those cells in which a single receptor allows the best possible Ag
      response, and on molecular restrictions of gene accessibility to rearrangement.
      The extent to which transcriptional control may be involved is unclear.
      Transcripts arising from nonfunctional alleles would undergo nonsense-mediated
      degradation and their virtual absence in mature cells cannot ensure that
      transcription per se is down-regulated. By contrast, somatic hypermutation may
      provide an estimate of primary transcription in Ag-activated cells since both
      processes are directly correlated. For coding regions, the rate and nature of
      mutations also depend upon Ag binding constraints. By sequencing intronic
      sequence downstream mouse VDJ genes, we could show in the absence of such
      constraints that somatic hypermutation intrinsically targets nonfunctional
      rearranged alleles at a frequency approaching that of functional alleles,
      suggesting that transcription also proceeds on both alleles at a similar rate. By
      contrast and confirming the strong dependency of somatic hypermutation upon
      transcription, we show that artificial blockade of transcription on the
      nonfunctional allele by a knock-in neomycin resistance cassette keeps the VDJ
      region unmutated even when its promoter is intact and when it is fully
      rearranged.

PMID- 15265917
TI  - De novo synthesized RelB mediates TNF-induced up-regulation of the human
      polymeric Ig receptor.
AB  - Secretory Abs, which operate in a principally noninflammatory fashion, constitute
      the first line of acquired immune defense of mucosal surfaces. Such Abs are
      generated by polymeric Ig receptor (pIgR)-mediated export of dimeric IgA and
      pentameric IgM. TNF activates a proinflammatory gene repertoire in mucosal
      epithelial cells and also enhances pIgR expression. In this study we show that
      TNF-induced up-regulation of the human pIgR critically depends on an NF-kappa B
      site and flanking sequences within a 204-bp region of the first intron in the
      pIgR gene, a region largely overlapping with a recently characterized IL-4
      responsive enhancer. The intronic NF-kappa B site was rapidly bound by NF-kappa B
      p65/p50 heterodimers present in nuclear extracts after TNF treatment of HT-29
      cells, but a more delayed binding of RelB agreed better with the slow, protein
      synthesis-dependent, transcriptional activation of the pIgR gene. Overexpression
      of NF-kappa B p65 caused transient up-regulation of a pIgR-derived reporter gene,
      whereas overexpression of RelB showed a stronger and more sustained effect.
      Finally, we demonstrated that inhibition of endogenous RelB by RNA interference
      severely reduced the TNF responsiveness of our pIgR-derived reporter gene. Thus,
      TNF-induced signaling pathways required for up-regulated pIgR expression appear
      to differ from those of the proinflammatory gene repertoire.

PMID- 15265918
TI  - Endogenous expression of activation-induced cytidine deaminase in cell line WEHI
      231.
AB  - Because of its susceptibility to apoptosis on Ag receptor cross-linking, cells of
      the mouse cell line WEHI-231 have been classified as immature B cells.
      Surprisingly, however, the cell line expresses activation-induced cytidine
      deaminase, the enzyme that mediates hypermutation and Ig class switch
      recombination in activated B cells. Although both cDNA sequence and protein
      expression of activation-induced cytidine deaminase appear normal, the cell line
      does not hypermutate an indicator plasmid. For the readout, the indicator plasmid
      depends on the removal of deoxyuridine after transition from C to U and,
      therefore, on functional expression of uracil N-glycosylase 2, which is normal in
      WEHI-231. At the endogenous Ig locus, however, WEHI-231 does undergo the
      canonical hypermutation of G. C to A. T base pairs to some extent. The cell line
      also expresses the germline transcripts of the Ig gamma 2b, epsilon, and alpha
      loci, but it does not switch its IgM surface Ig.

PMID- 15265919
TI  - Histidines are critical for heparin-dependent activation of mast cell tryptase.
AB  - Mast cell tryptase is a tetrameric serine protease that is stored in complex with
      negatively charged heparin proteoglycans in the secretory granule. Tryptase has
      potent proinflammatory properties and has been implicated in diverse pathological
      conditions such as asthma and fibrosis. Previous studies have shown that tryptase
      binds tightly to heparin, and that heparin is required in the assembly of the
      tryptase tetramer as well as for stabilization of the active tetramer. Because
      the interaction of tryptase with heparin is optimal at acidic pH, we investigated
      in this study whether His residues are of importance for the heparin binding,
      tetramerization, and activation of the tryptase mouse mast cell protease 6.
      Molecular modeling of mouse mast cell protease 6 identified four His residues,
      H35, H106, H108, and H238, that are conserved among pH-dependent tryptases and
      are exposed on the molecular surface, and these four His residues were mutated to
      Ala. In addition, combinations of different mutations were prepared. Generally,
      the single His-Ala mutations did not cause any major defects in heparin binding,
      activation, or tetramerization, although some effect of the H106A mutation was
      observed. However, when several mutations were combined, large defects in all of
      these parameters were observed. Of the mutants, the triple mutant
      H106A/H108A/H238A was the most affected with an almost complete inability to bind
      to heparin and to form active tryptase tetramers. Taken together, this study
      shows that surface-exposed histidines mediate the interaction of mast cell
      tryptase with heparin and are of critical importance in the formation of active
      tryptase tetramers.

PMID- 15265920
TI  - B cell lipid rafts regulate both peptide-dependent and peptide-independent APC-T
      cell interaction.
AB  - Formation of an immunological synapse (IS) between APCs and T CD4(+) lymphocytes
      is a key event in the initiation and the termination of the cognate immune
      response. We have analyzed the contribution of the APC to IS formation and report
      the implication of the actin cytoskeleton, the signaling proteins and the lipid
      rafts of B lymphocytes. Recruitment of MHC class II molecules to the IS is
      concomitant with actin cytoskeleton-dependent B cell raft recruitment. B cell
      actin cytoskeleton disruption abrogates both IS formation and T cell activation,
      whereas protein kinase C inhibition only impairs T cell activation.
      Pharmacological B cell lipid raft disruption inhibited peptide-dependent T
      lymphocyte activation and induced peptide-independent but HLA-DR-restricted APC-T
      cell conjugate formation. Such peptide-independent conjugates did not retain the
      ability to activate T cells. Thus, B cell lipid rafts are bifunctional by
      regulating T cell activation and imposing peptide stringency.

PMID- 15265921
TI  - IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the
      absence of IL-12.
AB  - IL-23 and IL-12 are heterodimeric cytokines which share the p40 subunit, but
      which have unique second subunits, IL-23p19 and IL-12p35. Since p40 is required
      for the development of the Th1 type response necessary for resistance to
      Toxoplasma gondii, studies were performed to assess the role of IL-23 in
      resistance to this pathogen. Increased levels of IL-23 were detected in mice
      infected with T. gondii and in vitro stimulation of dendritic cells with this
      pathogen resulted in increased levels of mRNA for this cytokine. To address the
      role of IL-23 in resistance to T. gondii, mice lacking the p40 subunit (common to
      IL-12 and IL-23) and mice that lack IL-12 p35 (specific for IL-12) were infected
      and their responses were compared. These studies revealed that p40(-/-) mice
      rapidly succumbed to toxoplasmosis, while p35(-/-) mice displayed enhanced
      resistance though they eventually succumbed to this infection. In addition, the
      administration of IL-23 to p40(-/-) mice infected with T. gondii resulted in a
      decreased parasite burden and enhanced resistance. However, the enhanced
      resistance of p35(-/-) mice or p40(-/-) mice treated with IL-23 was not
      associated with increased production of IFN-gamma. When IL-23p19(-/-) mice were
      infected with T. gondii these mice developed normal T cell responses and
      controlled parasite replication to the same extent as wild-type mice. Together,
      these studies indicate that IL-12, not IL-23, plays a dominant role in resistance
      to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited
      mechanism of resistance to this infection.

PMID- 15265922
TI  - Innate BALB/c enteric epithelial responses to Trichinella spiralis: inducible
      expression of a novel goblet cell lectin, intelectin-2, and its natural deletion
      in C57BL/10 mice.
AB  - Infection of mice with the nematode parasite Trichinella spiralis induces changes
      in the proteome of the jejunal epithelium, including substantial up-regulation of
      a novel variant of interlectin. In this study we sequence this novel lectin,
      termed intelectin-2, and compare expression levels during T. spiralis infection
      of resistant (BALB/c) with susceptible (C57BL/10) mouse strains. Intelectin-2 was
      cloned and sequenced from BALB/c mRNA extracted on day 14 of infection, and was
      found to have 91% amino acid identity with intelectin (within our study termed
      intelectin-1). Intelectin-2 transcripts were up-regulated early (day 3) during
      infection with T. spiralis in BALB/c mice, suggesting an innate response, and
      levels remained high through to day 14 (time of parasite rejection).
      Immunohistochemistry of jejunal sections with a rabbit polyclonal Ab to Xenopus
      laevis 35-kDa cortical granule lectin (XL35; 68% identity with intelectin-2)
      followed a similar pattern, with intense labeling of goblet and Paneth cells at
      day 14. However, intelectin-2 transcripts and protein were absent, and
      immunohistochemistry negative when C57BL/10 mice were infected with T. spiralis.
      Genomic PCR and Southern blotting confirmed that the intelectin-2 gene is absent
      from the C57BL/10 genome. The presence of intelectin-2 in resistant BALB/c mice,
      its absence from the susceptible C57BL/10 strain and the kinetics of its up
      regulation during T. spiralis infection suggest that this novel lectin may serve
      a protective role in the innate immune response to parasite infection.

PMID- 15265923
TI  - LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune
      recognition.
AB  - Although Gal beta 1-4GlcNAc (LacNAc) moieties are the most common constituents of
      N-linked glycans on vertebrate proteins, GalNAc beta 1-4GlcNAc (LacdiNAc, LDN)
      containing glycans are widespread in invertebrates, such as helminths. We
      postulated that LDN might be a molecular pattern for recognition of helminth
      parasites by the immune system. Using LDN-based affinity chromatography and mass
      spectrometry, we have identified galectin-3 as the major LDN-binding protein in
      macrophages. By contrast, LDN binding was not observed with galectin-1. Surface
      plasmon resonance (SPR) analysis and a solid phase binding assay demonstrated
      that galectin-3 binds directly to neoglycoconjugates carrying LDN glycans. In
      addition, galectin-3 bound to Schistosoma mansoni soluble egg Ags and a mAb
      against the LDN glycan inhibited this binding, suggesting that LDN glycans within
      S. mansoni soluble egg Ags contribute to galectin-3 binding. Immunocytochemistry
      demonstrated high levels of galectin-3 in liver granulomas of S. mansoni-infected
      hamsters, and a colocalization of galectin-3 and LDN glycans was observed on the
      parasite eggshells. Finally, we demonstrate that galectin-3 can mediate
      recognition and phagocytosis of LDN-coated particles by macrophages. These
      findings provide evidence that LDN-glycans constitute a parasite pattern for
      galectin-3-mediated immune recognition.

PMID- 15265924
TI  - MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse
      provides a site for immune generation following vaginal herpes simplex virus-2
      infection.
AB  - The members of the lymphotoxin (LT) family of molecules play a critical role in
      lymphoid organogenesis. Whereas LT alpha-deficient mice lack all lymph nodes and
      Peyer's patches, mice deficient in LT beta retain mesenteric lymph nodes and
      cervical lymph nodes, suggesting that an LT beta-independent pathway exists for
      the generation of mucosal lymph nodes. In this study, we describe the presence of
      a lymph node in LT beta-deficient mice responsible for draining the genital
      mucosa. In the majority of LT beta-deficient mice, a lymph node was found near
      the iliac artery, slightly misplaced from the site of the sacral lymph node in
      wild-type mice. The sacral lymph node of the LT beta-deficient mice, as well as
      that of the wild-type mice, expressed the mucosal addressin cell adhesion
      molecule-1 similar to the mesenteric lymph node. Following intravaginal infection
      with HSV type 2, activated dendritic cells capable of stimulating a Th1 response
      were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG
      responses were generated in the LT beta-deficient mice following intravaginal HSV
      2 infection even in the absence of the spleen. Therefore, an LT beta-independent
      pathway exists for the development of a lymph node associated with the genital
      mucosa, and such a lymph node serves to generate potent immune responses against
      viral challenge.

PMID- 15265925
TI  - Innate immune responses to Rhodococcus equi.
AB  - We examined innate immune responses to the intracellular bacterium Rhodococcus
      equi and show that infection of macrophages with intact bacteria induced the
      rapid translocation of NF-kappa B and the production of a variety of
      proinflammatory mediators, including TNF, IL-12, and NO. Macrophages from mice
      deficient in MyD88 failed to translocate NF-kappa B and produced virtually no
      cytokines in response to R. equi infection, implicating a TLR pathway. TLR4 was
      not involved in this response, because C3H/HeJ macrophages were fully capable of
      responding to R. equi infection, and because RAW-264 cells transfected with a
      dominant negative form of TLR4 responded normally to infection by R. equi. A
      central role for TLR2 was identified. A TLR2 reporter cell was activated by R.
      equi, and RAW-264 cells transfected with a dominant negative TLR2 exhibited
      markedly reduced cytokine responses to R. equi. Moreover, macrophages from TLR2(
      /-) mice exhibited diminished cytokine responses to R. equi. The role of the
      surface-localized R. equi lipoprotein VapA (virulence-associated protein A), in
      TLR2 activation was examined. Purified rVapA activated a TLR2-specific reporter
      cell, and it induced the maturation of dendritic cells and the production of
      cytokines from macrophages. Importantly, TLR2(-/-)-deficient but not TLR4(-/-)
      deficient mice were found to be compromised in their ability to clear a challenge
      with virulent R. equi. We conclude that the efficient activation of innate
      immunity by R. equi may account for the relative lack of virulence of this
      organism in immunocompetent adults.

PMID- 15265926
TI  - Wheat gluten causes dendritic cell maturation and chemokine secretion.
AB  - Wheat gluten causes gut inflammation in genetically predisposed individuals. We
      tested the hypothesis that wheat gluten is not only a target of adaptive
      immunity, but also modulates the function of APC. Dendritic cells (DC) derived
      from the bone marrow of BALB/c mice were exposed to chymotrypsin-treated wheat
      gluten. This induced DC maturation as estimated by all surface markers tested
      (MHC class II, CD40, CD54, and CD86). The effect was dose dependent, and, at 100
      microg/ml gluten matched that caused by 10 ng/ml LPS. A role of endotoxin
      contamination was ruled out by demonstrating the resistance of wheat gluten
      effects to LPS antagonist polymyxin B. DC from LPS nonresponder strain C3H/HeJ
      were affected by wheat gluten, but not by LPS. Proteinase K-digested wheat gluten
      was unable to stimulate DC maturation. Wheat gluten induced a unique secretion
      pattern of selected cytokines and chemokines in DC. Classic pro- or anti
      inflammatory mediators were not produced, in contrast to LPS. Rather, chemokines
      MIP-2 and keratinocyte-derived cytokine were secreted in large amounts. We
      conclude that wheat gluten lowers the threshold for immune responses by causing
      maturation of APC, by attracting leukocytes and increasing their reactivity
      state. In the presence of an appropriate genetic predisposition, this is expected
      to increase the risk of adverse immune reactions to wheat gluten or to other Ags
      presented.

PMID- 15265927
TI  - Bordetella type III secretion and adenylate cyclase toxin synergize to drive
      dendritic cells into a semimature state.
AB  - Bordetella bronchiseptica establishes persistent infection of the murine
      respiratory tract. We hypothesize that long-term colonization is mediated in part
      by bacteria-driven modulation of dendritic cells (DCs) leading to altered
      adaptive immune responses. Bone marrow-derived DCs (BMDCs) from C57BL/6 mice
      infected with live B. bronchiseptica exhibited high surface expression of MHCII,
      CD86, and CD80. However, B. bronchiseptica-infected BMDCs did not exhibit
      significant increases in CD40 surface expression and IL-12 secretion compared
      with BMDCs treated with heat-killed B. bronchiseptica. The B. bronchiseptica type
      III secretion system (TTSS) mediated the increase in MHCII, CD86, and CD80
      surface expression, while the inhibition of CD40 and IL-12 expression was
      mediated by adenylate cyclase toxin (ACT). IL-6 secretion was independent of the
      TTSS and ACT. These phenotypic changes may result from differential regulation of
      MAPK signaling in DCs. Wild-type B. bronchiseptica activated the ERK 1/2
      signaling pathway in a TTSS-dependent manner. Additionally, ACT was found to
      inhibit p38 signaling. These data suggest that B. bronchiseptica drive DC into a
      semimature phenotype by altering MAPK signaling. These semimature DCs may induce
      tolerogenic immune responses that allow the persistent colonization of B.
      bronchiseptica in the host respiratory tract.

PMID- 15265928
TI  - Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine
      induced CTL.
AB  - Recognition by CD8(+) T lymphocytes (CTL) of epitopes that are derived from
      conserved gene products, such as Gag and Pol, is well documented and conceptually
      supports the development of epitope-based vaccines for use against diverse HIV-1
      subtypes. However, many CTL epitopes from highly conserved regions within the HIV
      1 genome are highly variable, when assessed by comparison of amino acid
      sequences. The TCR is somewhat promiscuous with respect to peptide binding, and,
      as such, CTL can often recognize related epitopes. In these studies, we evaluated
      CTL recognition of five sets of variant HIV-1 epitopes restricted to HLA-A*0201
      and HLA-A*1101 using HLA transgenic mice. We found that numerous different amino
      acid substitutions can be introduced into epitopes without abrogating their
      recognition by CTL. Based on our findings, we constructed an algorithm to predict
      those CTL epitopes capable of inducing responses in the HLA transgenic mice to
      the greatest numbers of variant epitopes. Similarity of CTL specificity for
      variant epitopes was demonstrated for humans using PBMC from HIV-1-infected
      individuals and CTL lines produced in vitro using PBMC from HIV-1-uninfected
      donors. We believe the ability to predict CTL epitope immunogenicity and
      recognition patterns of variant epitopes can be useful for designing vaccines
      against multiple subtypes and circulating recombinant forms of HIV-1.

PMID- 15265929
TI  - Th cell-independent immune responses to chimeric hemagglutinin/simian human
      immunodeficiency virus-like particles vaccine.
AB  - CD4(+) Th cells are believed to be essential for the induction of humoral and
      cellular immune responses. In this study we tested the effect and possible
      mechanisms of the major antigenic component in influenza, hemagglutinin (HA), in
      helping HIV Env to induce immune responses in CD4(+) T cell knockout (CD4 KO)
      mice. Simian HIV virus-like particles (SHIV VLPs) or phenotypically mixed
      chimeric influenza HA/SHIV VLPs were used as immunogens to immunize CD4 KO mice
      either i.p. or intranasally (i.n.). We found that chimeric HA/SHIV VLPs
      significantly induced a greater IgG Ab response in both i.p. and i.n. immunized
      mice and a greater IgA Ab response in mucosal washes in i.n. immunized mice
      compared with SHIV VLPs. Importantly, chimeric HA/SHIV VLPs induced approximately
      3-fold higher neutralizing Ab titers against HIV 89.6 than SHIV VLPs in the
      absence of CD4(+) T cell help. There was also approximately 40% more specific
      lysis of the HIV Env-expressing target cells in chimeric HA/SHIV VLP-immunized
      than in SHIV VLP-immunized CD4 KO mouse splenocytes. Moreover, we have found that
      chimeric HA/SHIV VLPs could efficiently bind and activate dendritic cells and
      stimulate the activated dendritic cells to secret TNF-alpha and IFN-gamma.
      Therefore, chimeric HA/SHIV VLPs could efficiently prime and activate APCs, which
      could, in turn, induce immune responses in a CD4(+) T cell-independent manner.
      This study suggests a novel adjuvant role of influenza HA as well as a new
      strategy to develop more effective therapeutic vaccines for AIDS patients with
      low CD4(+) T cell counts.

PMID- 15265930
TI  - Bordetella pertussis lipopolysaccharide resists the bactericidal effects of
      pulmonary surfactant protein A.
AB  - Surfactant protein A (SP-A) plays an important role in the innate immune defense
      of the respiratory tract. SP-A binds to lipid A of bacterial LPS, induces
      aggregation, destabilizes bacterial membranes, and promotes phagocytosis by
      neutrophils and macrophages. In this study, SP-A interaction with wild-type and
      mutant LPS of Bordetella pertussis, the causative agent of whooping cough, was
      examined. B. pertussis LPS has a branched core structure with a nonrepeating
      trisaccharide, rather than a long-chain repeating O-Ag. SP-A did not bind,
      aggregate, nor permeabilize wild-type B. pertussis. LPS mutants lacking even one
      of the sugars in the terminal trisaccharide were bound and aggregated by SP-A. SP
      A enhanced phagocytosis by human monocytes of LPS mutants that were able to bind
      SP-A, but not wild-type bacteria. SP-A enhanced phagocytosis by human neutrophils
      of LPS-mutant strains, but only in the absence of functional adenylate cyclase
      toxin, a B. pertussis toxin that has been shown to depress neutrophil activity.
      We conclude that the LPS of wild-type B. pertussis shields the bacteria from SP-A
      mediated clearance, possibly by sterically limiting access to the lipid A region.

PMID- 15265931
TI  - Characterization of a Mycobacterium tuberculosis peptide that is recognized by
      human CD4+ and CD8+ T cells in the context of multiple HLA alleles.
AB  - The secreted Mycobacterium tuberculosis 10-kDa culture filtrate protein (CFP)10
      is a potent T cell Ag that is recognized by a high percentage of persons infected
      with M. tuberculosis. We determined the molecular basis for this widespread
      recognition by identifying and characterizing a 15-mer peptide, CFP10(71-85),
      that elicited IFN-gamma production and CTL activity by both CD4(+) and CD8(+) T
      cells from persons expressing multiple MHC class II and class I molecules,
      respectively. CFP10(71-85) contained at least two epitopes, one of 10 aa (peptide
      T1) and another of 9 aa (peptide T6). T1 was recognized by CD4(+) cells in the
      context of DRB1*04, DR5*0101, and DQB1*03, and by CD8(+) cells of A2(+) donors.
      T6 elicited responses by CD4(+) cells in the context of DRB1*04 and DQB1*03, and
      by CD8(+) cells of B35(+) donors. Deleting a single amino acid from the amino or
      carboxy terminus of either peptide markedly reduced IFN-gamma production,
      suggesting that they are minimal epitopes for both CD4(+) and CD8(+) cells. As
      far as we are aware, these are the shortest microbial peptides that have been
      found to elicit responses by both T cell subpopulations. The capacity of CFP10(71
      85) to stimulate IFN-gamma production and CTL activity by CD4(+) and CD8(+) cells
      from persons expressing a spectrum of MHC molecules suggests that this peptide is
      an excellent candidate for inclusion in a subunit antituberculosis vaccine.

PMID- 15265932
TI  - Role of IgA versus IgG in the control of influenza viral infection in the murine
      respiratory tract.
AB  - The roles of IgG and secretory IgA in the protection of the respiratory tract
      (RT) against influenza infection remain unclear. Passive immunization with Ab
      doses resulting in serum IgG anti-influenza virus Ab titers far in excess of
      those observed in immune mice has compounded the problem. We compared the effects
      of i.v. anti-influenza virus IgG and i.v. anti-influenza virus polymeric IgA
      (pIgA) mAb administered in amounts designed to replicate murine convalescent
      serum or nasal Ab titers, respectively. A serum anti-influenza virus IgG titer
      2.5 times the normal convalescent serum anti-influenza virus IgG titer was
      required for detectible Ab transudation into nasal secretions, and a serum IgG
      titer 7 times normal was needed to lower nasal viral shedding by 98%. Anti
      influenza virus pIgA at a nasal Ab titer comparable to that seen in convalescent
      mice eliminated nasal viral shedding. The RT of influenza-infected pIgA- or IgG
      protected mice were studied by scanning electron microscopy. Only pIgA was found
      to prevent virally induced pathology in the upper RT, suggesting that IgG did not
      prevent viral infection of the nose, but neutralized newly replicated virus after
      infection had been initiated. In contrast, IgG, but not pIgA, was found to
      prevent viral pathology in the murine lung. Our results help to resolve the
      controversy of IgA- vs IgG-mediated protection of the RT; both Abs are important,
      with plasma IgG Ab serving as the back-up for secretory IgA-mediated protection
      in the nasal compartment, and IgG being the dominant Ab in protection of the
      lung.

PMID- 15265933
TI  - Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA
      class I and class II.
AB  - Strong CD4(+) and CD8(+) T cell responses are considered important immune
      components for controlling HIV infection, and their priming may be central to an
      effective HIV vaccine. We describe in this study an approach by which multiple
      CD4(+) and CD8(+) T cell epitopes are processed and presented from an exogenously
      added HIV-1 Gag-p24 peptide of 32 aa complexed to heat shock protein (HSP) gp96.
      CD8(+) T cell recognition of the HSP/peptide complex, but not the peptide alone,
      was inhibited by brefeldin A, suggesting an endoplasmic reticulum-dependent
      pathway. This is the first report to describe efficient processing and
      simultaneous presentation of overlapping class I- and class II-restricted
      epitopes from the same extracellularly added precursor peptide complexed to HSP.
      Given previous reports of the strong immunogenicity of HSP/peptide complexes, the
      present data suggest that HSP-complexed peptides containing multiple MHC class I-
      and class II-restricted epitopes represent potential vaccine candidates for HIV
      and other viral infections suitable to induce effective CTL memory by
      simultaneously providing CD4 T cell help.

PMID- 15265934
TI  - Neutrophil involvement in cross-priming CD8+ T cell responses to bacterial
      antigens.
AB  - Substantial CD8(+) T cell responses are generated after infection of mice with
      recombinant Listeria monocytogenes strains expressing a model epitope
      (lymphocytic choriomeningitis virus NP(118-126)) in secreted and nonsecreted
      forms. L. monocytogenes gains access to the cytosol of infected cells, where
      secreted Ags can be accessed by the endogenous MHC class I presentation pathway.
      However, the route of presentation of the nonsecreted Ag in vivo remains
      undefined. In this study we show that neutrophil-enriched peritoneal exudate
      cells from L. monocytogenes-infected mice can serve as substrates for in vitro
      cross-presentation of both nonsecreted and secreted Ag by dendritic cells as well
      as for in vivo cross-priming of CD8(+) T cells. In addition, specific neutrophil
      depletion in vivo by low dose treatment with either of two Ly6G-specific mAb
      substantially decreased the relative CD8(+) T cell response against the
      nonsecreted, but not the secreted, Ag compared with control Ab-treated mice.
      Thus, neutrophils not only provide rapid innate defense against infection, but
      also contribute to shaping the specificity and breadth of the CD8(+) T cell
      response. In addition, cross-presentation of bacterial Ags from neutrophils may
      explain how CD8(+) T cell responses are generated against Ags from extracellular
      bacterial pathogens.

PMID- 15265935
TI  - MyD88 plays a unique role in host defense but not arthritis development in Lyme
      disease.
AB  - To assess the contribution of TLR signaling in the host response to Borrelia
      burgdorferi, mice deficient in the common TLR adaptor protein, myeloid
      differentiation factor 88 (MyD88), were infected with B. burgdorferi. MyD88
      deficient mice harbored extremely high levels of B. burgdorferi in tissues when
      compared with wild-type littermates and greater amounts of spirochetes in tissues
      than TLR2-deficient mice. These findings suggest that, in addition to TLR2, other
      MyD88-dependent pathways play a significant role in the host defense to B.
      burgdorferi. MyD88(-/-) mice maintained the ability to produce Abs directed
      against B. burgdorferi. Partial clearance of spirochetes was evident in long term
      infection studies and immune sera from MyD88-deficient mice were able to protect
      naive mice from infection with B. burgdorferi. Thus, the acquired immune response
      appeared to be functional in MyD88(-/-) mice, and the inability to control
      spirochete numbers was due to a failure of cells involved in innate defenses.
      Although macrophages from MyD88(-/-) mice responded poorly to Borrelia sonicate
      in vitro, MyD88(-/-) mice still developed an inflammatory arthritis after
      infection with B. burgdorferi characterized by an influx of neutrophils and
      mononuclear cells. The findings presented here point to a dichotomy between the
      recruitment of inflammatory cells to tissue and an inability of these cells to
      kill localized spirochetes.

PMID- 15265936
TI  - Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B
      activation through inhibition of activation of I kappa B alpha kinase and Akt in
      human non-small cell lung carcinoma: correlation with suppression of COX-2
      synthesis.
AB  - The cyclooxygenase 2 (COX-2) inhibitor celecoxib (also called celebrex), approved
      for the treatment of colon carcinogenesis, rheumatoid arthritis, and other
      inflammatory diseases, has been shown to induce apoptosis and inhibit
      angiogenesis. Because NF-kappa B plays a major role in regulation of apoptosis,
      angiogenesis, carcinogenesis, and inflammation, we postulated that celecoxib
      modulates NF-kappa B. In the present study, we investigated the effect of this
      drug on the activation of NF-kappa B by a wide variety of agents. We found that
      celecoxib suppressed NF-kappa B activation induced by various carcinogens,
      including TNF, phorbol ester, okadaic acid, LPS, and IL-1 beta. Celecoxib
      inhibited TNF-induced I kappa B alpha kinase activation, leading to suppression
      of I kappa B alpha phosphorylation and degradation. Celecoxib suppressed both
      inducible and constitutive NF-kappa B without cell type specificity. Celecoxib
      also suppressed p65 phosphorylation and nuclear translocation. Akt activation,
      which is required for TNF-induced NF-kappa B activation, was also suppressed by
      this drug. Celecoxib also inhibited the TNF-induced interaction of Akt with I
      kappa B alpha kinase (IKK). Celecoxib abrogated the NF-kappa B-dependent reporter
      gene expression activated by TNF, TNF receptor, TNF receptor-associated death
      domain, TNF receptor-associated factor 2, NF-kappa B-inducing kinase, and IKK,
      but not that activated by p65. The COX-2 promoter, which is regulated by NF-kappa
      B, was also inhibited by celecoxib, and this inhibition correlated with
      suppression of TNF-induced COX-2 expression. Besides NF-kappa B, celecoxib also
      suppressed TNF-induced JNK, p38 MAPK, and ERK activation. Thus, overall, our
      results indicate that celecoxib inhibits NF-kappa B activation through inhibition
      of IKK and Akt activation, leading to down-regulation of synthesis of COX-2 and
      other genes needed for inflammation, proliferation, and carcinogenesis.

PMID- 15265937
TI  - Heme inhibits human neutrophil apoptosis: involvement of phosphoinositide 3
      kinase, MAPK, and NF-kappaB.
AB  - High levels of free heme are found in pathological states of increased hemolysis,
      such as sickle cell disease, malaria, and ischemia reperfusion. The hemolytic
      events are often associated with an inflammatory response that usually turns into
      chronic inflammation. We recently reported that heme is a proinflammatory
      molecule, able to induce neutrophil migration, reactive oxygen species
      generation, and IL-8 expression. In this study, we show that heme (1-50 microM)
      delays human neutrophil spontaneous apoptosis in vitro. This effect requires heme
      oxygenase activity, and depends on reactive oxygen species production and on de
      novo protein synthesis. Inhibition of ERK and PI3K pathways abolished heme
      protective effects upon human neutrophils, suggesting the involvement of the
      Ras/Raf/MAPK and PI3K pathway on this effect. Confirming the involvement of these
      pathways in the modulation of the antiapoptotic effect, heme induces Akt
      phosphorylation and ERK-2 nuclear translocation in neutrophils. Futhermore,
      inhibition of NF-kappa B translocation reversed heme antiapoptotic effect. NF
      kappa B (p65 subunit) nuclear translocation and I kappa B degradation were also
      observed in heme-treated cells, indicating that free heme may regulate neutrophil
      life span modulating signaling pathways involved in cell survival. Our data
      suggest that free heme associated with hemolytic episodes might play an important
      role in the development of chronic inflammation by interfering with the longevity
      of neutrophils.

PMID- 15265938
TI  - Different domains of Pseudomonas aeruginosa exoenzyme S activate distinct TLRs.
AB  - Some bacterial products possess multiple immunomodulatory effects and thereby
      complex mechanisms of action. Exogenous administration of an important
      Pseudomonas aeruginosa virulence factor, exoenzyme S (ExoS) induces potent
      monocyte activation leading to the production of numerous proinflammatory
      cytokines and chemokines. However, ExoS is also injected directly into target
      cells, inducing cell death through its multiple effects on signaling pathways.
      This study addresses the mechanisms used by ExoS to induce monocyte activation.
      Exogenous administration resulted in specific internalization of ExoS via an
      actin-dependent mechanism. However, ExoS-mediated cellular activation was not
      inhibited if internalization was blocked, suggesting an alternate mechanism of
      activation. ExoS bound a saturable and specific receptor on the surface of
      monocytic cells. ExoS, LPS, and peptidoglycan were all able to induce tolerance
      and cross-tolerance to each other suggesting the involvement of a TLR in ExoS
      recognition. ExoS activated monocytic cells via a myeloid differentiation Ag-88
      pathway, using both TLR2 and the TLR4/MD-2/CD14 complex for cellular activation.
      Interestingly, the TLR2 activity was localized to the C-terminal domain of ExoS
      while the TLR4 activity was localized to the N-terminal domain. This study
      provides the first example of how different domains of the same molecule activate
      two TLRs, and also highlights the possible overlapping pathophysiological
      processes possessed by microbial toxins.

PMID- 15265939
TI  - Phenyl methimazole inhibits TNF-alpha-induced VCAM-1 expression in an IFN
      regulatory factor-1-dependent manner and reduces monocytic cell adhesion to
      endothelial cells.
AB  - Proinflammatory cytokine (e.g., TNF-alpha)-induced expression of endothelial cell
      adhesion molecules (ECAMs) on the lumenal surface of the vascular endothelium and
      a consequent increase in leukocyte adhesion are key aspects of pathological
      inflammation. A promising therapeutic approach to diminish aberrant leukocyte
      adhesion is, therefore, to inhibit cytokine-induced ECAM expression at the
      transcription level. Several studies suggest that methimazole, a compound used
      clinically to treat autoimmune diseases, such as Graves' disease, may also
      diminish pathological inflammation by suppressing ECAM expression. In this study
      we probed the hypothesis that a derivative of methimazole, phenyl methimazole
      (compound 10), can reduce cytokine-induced ECAM expression and consequent
      leukocyte adhesion. We found that compound 10 1) dramatically inhibits TNF-alpha
      induced VCAM-1 mRNA and protein expression in human aortic endothelial cells
      (HAEC), has a relatively modest inhibitory effect on TNF-alpha induced E-selectin
      expression and has no effect on ICAM-1 expression; 2) significantly reduces TNF
      alpha-induced monocytic (U937) cell adhesion to HAEC under in vitro flow
      conditions similar to that present in vivo; 3) inhibits TNF-alpha-induced IFN
      regulatory factor-1 binding to VCAM-1 promoter; and 4) reduces TNF-alpha-induced
      IRF-1 expression in HAEC. Combined, the results indicate that phenyl methimazole
      can reduce TNF-alpha-induced VCAM-1 expression in an IFN regulatory factor-1
      dependent manner and that this contributes significantly to reduced monocytic
      cell adhesion to TNF-alpha-activated HAEC.

PMID- 15265940
TI  - Blockade of CXCR3 receptor:ligand interactions reduces leukocyte recruitment to
      the lung and the severity of experimental idiopathic pneumonia syndrome.
AB  - Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication after
      allogeneic stem cell transplantation (allo-SCT) that responds poorly to standard
      immunosuppressive therapy. The pathophysiology of IPS involves the secretion of
      inflammatory cytokines including IFN-gamma and TNF-alpha along with the
      recruitment of donor T cells to the lung. CXCR3 is a chemokine receptor that is
      expressed on activated Th1/Tc1 T cell subsets and the expression of its ligands
      CXCL9 (monokine induced by IFN-gamma (Mig)) and CXCL10 (IFN-gamma-inducible
      protein 10 (IP-10)) can be induced in a variety of cell types by IFN-gamma alone
      or in combination with TNF-alpha. We used a lethally irradiated murine SCT model
      (B6 --> bm1) to evaluate the role of CXCR3 receptor:ligand interactions in the
      development of IPS. We found that Mig and IP-10 protein levels were significantly
      elevated in the bronchoalveolar lavage fluid of allo-SCT recipients compared with
      syngeneic controls and correlated with the infiltration of IFN-gamma-secreting
      CXCR3(+) donor T cells into the lung. The in vivo neutralization of either Mig or
      IP-10 significantly reduced the severity of IPS compared with control-treated
      animals, and an additive effect was observed when both ligands were blocked
      simultaneously. Complementary experiments using CXCR3(-/-) mice as SCT donors
      also resulted in a significant decrease in IPS. These data demonstrate that
      interactions involving CXCR3 and its primary ligands Mig and IP-10 significantly
      contribute to donor T cell recruitment to the lung after allo-SCT. Therefore,
      approaches focusing on the abrogation of these interactions may prove successful
      in preventing or treating lung injury that occurs in this setting.

PMID- 15265941
TI  - Platelet factor 4/CXCL4 induces phagocytosis and the generation of reactive
      oxygen metabolites in mononuclear phagocytes independently of Gi protein
      activation or intracellular calcium transients.
AB  - Platelet factor 4 (PF-4), a platelet-derived CXC chemokine, is known to prevent
      human monocytes from apoptosis and to promote differentiation of these cells into
      HLA-DR(-) macrophages. In this study, we investigated the role of PF-4 in the
      control of acute monocyte proinflammatory responses involved in the direct combat
      of microbial invaders. We show that PF-4 increases monocyte phagocytosis and
      provokes a strong formation of oxygen radicals but lacks a chemotactic activity
      in these cells. Compared with FMLP, PF-4-induced oxidative burst was later in its
      onset but was remarkably longer in its duration (lasting for up to 60 min).
      Furthermore, in PF-4-prestimulated cells, FMLP- as well as RANTES-induced burst
      responses became synergistically enhanced. As we could show, PF-4-mediated
      oxidative burst in monocytes does not involve Gi proteins, elevation of
      intracellular free calcium concentrations, or binding to CXCR3B, a novel PF-4
      receptor recently discovered on endothelial cells. Moreover, we found that PF-4
      acts on macrophages in a dual manner. On the one hand, very similar to GM-CSF or
      M-CSF, PF-4 treatment of monocytes generates macrophages with a high capacity for
      unspecific phagocytosis. On the other hand, short term priming of GM-CSF-induced
      human macrophages with PF-4 substantially increases their capability for particle
      ingestion and oxidative burst. A comparable effect was also observed in murine
      bone marrow-derived macrophages, indicating cross-reactivity of human PF-4
      between both species. Taken together, PF-4 may play a crucial role in the
      induction and maintenance of an unspecific immune response.

PMID- 15265942
TI  - Responses of neutrophils to anti-integrin antibodies depends on costimulation
      through low affinity Fc gamma Rs: full activation requires both integrin and
      nonintegrin signals.
AB  - The relative contribution of integrin and nonintegrin signals to neutrophil
      activation is incompletely understood. Immobilized anti-integrin Abs were
      previously shown to induce robust activation of neutrophils without any
      additional stimulus, suggesting that cross-linking of integrins is sufficient for
      full activation of the cells. However, the possible contribution from other
      receptors has not been tested in this system. In this study, we show that
      neutrophil responses to anti-integrin Abs requires costimulation through low
      affinity Fc gamma Rs. Murine neutrophils lacking the FcR gamma-chain or Fc gamma
      RIII failed to respond to immobilized Abs against beta(1), beta(2), or beta(3)
      integrins and the activation of wild-type cells could be prevented by blocking
      Abs against Fc gamma RII/III. Plate-bound anti-CD18 Abs initiated a respiratory
      burst from human neutrophils, but this response was abrogated when the F(ab')(2)
      of the same Abs were used or the cells were preincubated with Fc gamma RIIA
      blocking Abs. Lack of Fc gamma RIII or administration of Fc gamma R-blocking Abs
      had no effect on responses of TNF-stimulated cells plated on fibrinogen or rICAM
      1. TNF restored the respiratory burst of Fc gamma RIII-deficient neutrophils
      plated on anti-CD18 mAbs. The p38 MAPK inhibitor SB203580 attenuated the
      responses of neutrophils to anti-CD18 mAbs or TNF stimulation on a fibrinogen
      surface. Taken together, these results indicate that activation of low-affinity
      Fc gamma Rs is required for neutrophil responses induced by anti-integrin Abs and
      suggest that a second coactivation signal (e.g., through TNF or FcR ligation) is
      indispensable for full integrin-mediated activation of neutrophils. These second
      signals are interchangeable and they may converge on the p38 MAPK.

PMID- 15265943
TI  - Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by
      interacting with histamine H4 receptor.
AB  - Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine that is
      constitutively expressed by the liver parenchymal cells and present in the normal
      plasma at high concentrations. Previous studies have shown that CCL16 is a low
      affinity ligand for CCR1, CCR2, CCR5, and CCR8 and attracts monocytes and T
      cells. Recently, a novel histamine receptor termed type 4 (H4) has been
      identified and shown to be selectively expressed by eosinophils and mast cells.
      In this study, we demonstrated that CCL16 induced pertussis toxin-sensitive
      calcium mobilization and chemotaxis in murine L1.2 cells expressing H4 but not
      those expressing histamine receptor type 1 (H1) or type 2 (H2). CCL16 bound to H4
      with a K(d) of 17 nM. By RT-PCR, human and mouse eosinophils express H4 but not
      H3. Accordingly, CCL16 induced efficient migratory responses in human and mouse
      eosinophils. Furthermore, the responses of human and mouse eosinophils to CCL16
      were effectively suppressed by thioperamide, an antagonist for H3 and H4.
      Intravenous injection of CCL16 into mice induced a rapid mobilization of
      eosinophils from bone marrow to peripheral blood, which was also suppressed by
      thioperamide. Collectively, CCL16 is a novel functional ligand for H4 and may
      have a role in trafficking of eosinophils.

PMID- 15265944
TI  - MIP-1 gamma promotes receptor-activator-of-NF-kappa-B-ligand-induced osteoclast
      formation and survival.
AB  - Chemokines play an important role in immune and inflammatory responses by
      inducing migration and adhesion of leukocytes, and have also been reported to
      modulate osteoclast differentiation from hemopoietic precursor cells of the
      monocyte-macrophage lineage. In this study, we examined the effect of MIP-1
      gamma, a C-C chemokine family member, on receptor activator of NF-kappa B ligand
      (RANKL)-stimulated osteoclast differentiation, survival, and activation. RANKL
      induced osteoclasts to dramatically increase production of MIP-1 gamma and to
      also express the MIP-1 gamma receptor CCR1, but had only minor effects on the
      related C-C chemokines MIP-1 alpha and RANTES. Neutralization of MIP-1 gamma with
      specific Ab reduced RANKL-stimulated osteoclast differentiation by 60-70%. Mature
      osteoclasts underwent apoptosis within 24 h after removal of RANKL, as shown by
      increased caspase 3 activity and DNA fragmentation. Apoptosis was reduced by the
      addition of exogenous MIP-1 gamma or RANKL, both of which increased NF-kappa B
      activation in osteoclasts. Neutralization studies showed that the prosurvival
      effect of RANKL was in part dependent on its ability to induce MIP-1 gamma.
      Finally, osteoclast activation for bone resorption was stimulated by MIP-1 gamma.
      Taken together, these results demonstrate that MIP-1 gamma plays an important
      role in the differentiation and survival of osteoclasts, most likely via an
      autocrine pathway.

PMID- 15265945
TI  - A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte
      specific protein 1 in human neutrophils.
AB  - Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory
      agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in
      several models of acute inflammation. In this study, we examined the effects of
      15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered
      lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of
      human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were
      found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by
      ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein
      1, a downstream component of the p38-MAPK cascade in neutrophils, by mass
      spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM)
      also reduced phosphorylation/activation of several components of the p38-MAPK
      pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated
      protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory
      effects, at least in part, by blocking activation of the p38-MAPK cascade in
      neutrophils, which is known to promote chemotaxis and other proinflammatory
      responses by these cells.

PMID- 15265946
TI  - Smad3 null mice develop airspace enlargement and are resistant to TGF-beta
      mediated pulmonary fibrosis.
AB  - Transforming growth factor-beta 1 plays a key role in the pathogenesis of
      pulmonary fibrosis, mediating extracellular matrix (ECM) gene expression through
      a series of intracellular signaling molecules, including Smad2 and Smad3. We show
      that Smad3 null mice (knockout (KO)) develop progressive age-related increases in
      the size of alveolar spaces, associated with high spontaneous presence of matrix
      metalloproteinases (MMP-9 and MMP-12) in the lung. Moreover, transient
      overexpression of active TGF-beta 1 in lungs, using adenoviral vector-mediated
      gene transfer, resulted in progressive pulmonary fibrosis in wild-type mice,
      whereas no fibrosis was seen in the lungs of Smad3 KO mice up to 28 days.
      Significantly higher levels of matrix components (procollagen 3A1, connective
      tissue growth factor) and antiproteinases (plasminogen activator inhibitor-1,
      tissue inhibitor of metalloproteinase-1) were detected in wild-type lungs 4 days
      after TGF-beta 1 administration, while no such changes were seen in KO lungs.
      These data suggest a pivotal role of the Smad3 pathway in ECM metabolism. Basal
      activity of the pathway is required to maintain alveolar integrity and ECM
      homeostasis, but excessive signaling through the pathway results in fibrosis
      characterized by inhibited degradation and enhanced ECM deposition. The Smad3
      pathway is involved in pathogenic mechanisms mediating tissue destruction (lack
      of repair) and fibrogenesis (excessive repair).

PMID- 15265947
TI  - Protective role of arginase in a mouse model of colitis.
AB  - Arginase is the endogenous inhibitor of inducible NO synthase (iNOS), because
      both enzymes use the same substrate, l-arginine (Arg). Importantly, arginase
      synthesizes ornithine, which is metabolized by the enzyme ornithine decarboxylase
      (ODC) to produce polyamines. We investigated the role of these enzymes in the
      Citrobacter rodentium model of colitis. Arginase I, iNOS, and ODC were induced in
      the colon during the infection, while arginase II was not up-regulated. l-Arg
      supplementation of wild-type mice or iNOS deletion significantly improved
      colitis, and l-Arg treatment of iNOS(-/-) mice led to an additive improvement.
      There was a significant induction of IFN-gamma, IL-1, and TNF-alpha mRNA
      expression in colitis tissues that was markedly attenuated with l-Arg treatment
      or iNOS deletion. Treatment with the arginase inhibitor S-(2-boronoethyl)-l
      cysteine worsened colitis in both wild-type and iNOS(-/-) mice. Polyamine levels
      were increased in colitis tissues, and were further increased by l-Arg. In
      addition, in vivo inhibition of ODC with alpha-difluoromethylornithine also
      exacerbated the colitis. Taken together, these data indicate that arginase is
      protective in C. rodentium colitis by enhancing the generation of polyamines in
      addition to competitive inhibition of iNOS. Modulation of the balance of iNOS and
      arginase, and of the arginase-ODC metabolic pathway may represent a new strategy
      for regulating intestinal inflammation.

PMID- 15265948
TI  - Nucleosome-specific regulatory T cells engineered by triple gene transfer
      suppress a systemic autoimmune disease.
AB  - The mechanisms of systemic autoimmune disease are poorly understood and available
      therapies often lead to immunosuppressive conditions. We describe here a new
      model of autoantigen-specific immunotherapy based on the sites of autoantigen
      presentation in systemic autoimmune disease. Nucleosomes are one of the well
      characterized autoantigens. We found relative splenic localization of the
      stimulative capacity for nucleosome-specific T cells in (NZB x NZW)F(1) (NZB/W
      F(1)) lupus-prone mice. Splenic dendritic cells (DCs) from NZB/W F(1) mice
      spontaneously stimulate nucleosome-specific T cells to a much greater degree than
      both DCs from normal mice and DCs from the lymph nodes of NZB/W F(1) mice. This
      leads to a strategy for the local delivery of therapeutic molecules using
      autoantigen-specific T cells. Nucleosome-specific regulatory T cells engineered
      by triple gene transfer (TCR-alpha, TCR-beta, and CTLA4Ig) accumulated in the
      spleen and suppressed the related pathogenic autoantibody production. Nephritis
      was drastically suppressed without impairing the T cell-dependent humoral immune
      responses. Thus, autoantigen-specific regulatory T cells engineered by multiple
      gene transfer is a promising strategy for treating autoimmune diseases.

PMID- 15265949
TI  - Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive,
      HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele.
AB  - According to a number of previous reports, control of HIV replication in humans
      appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses.
      During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected
      individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201
      recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the
      role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains
      controversial. In this study we determined whether the pattern of SL9
      immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to
      that seen in chronically HIV-infected subjects. The presence of anti-SL9
      responses was determined using a panel of highly sensitive cellular immunoassays,
      including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow
      cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL
      reactivities were tested, and none had a detectable anti-SL9 response. These
      findings strongly suggest that the pattern of SL9 epitope immunodominance
      previously reported among chronically infected, HLA-A*0201-positive patients is
      not recapitulated in noninfected recipients of Gag-containing canarypox-based
      candidate vaccines and may be influenced by the relative immunogenicity of these
      constructs.

PMID- 15265950
TI  - Type I IFN protects against murine lupus.
AB  - Both the type I (IFN-alpha beta) and type II (IFN-gamma) IFNs have been heavily
      implicated in the pathogenesis of systemic lupus erythematosus. To test the
      relative roles of these systems, congenic lupus-prone MRL/CD95(lpr/lpr) (MRL/lpr)
      mice lacking the type I IFN receptor (IFN-RI), type II IFN receptor (IFN-RII), or
      both, were derived. As expected, deficiency for IFN-RII protected MRL/lpr mice
      from the development of significant autoimmune-associated lymphadenopathy,
      autoantibodies, and renal disease. However, deficiency for the IFN-RI
      surprisingly worsened lymphoproliferation, autoantibody production, and end organ
      disease; animals doubly deficient for IFN-RI and IFN-RII developed an autoimmune
      phenotype intermediate between wild-type and IFN-RII-deficient animals, all
      correlating with an ability of type I IFN to suppress MRL B cell activation.
      Thus, type I IFNs protect against both the humoral and end organ autoimmune
      syndrome of MRL/lpr mice, independent of IFN-gamma. These findings warrant
      caution in the use of type I IFN antagonists in the treatment of autoimmune
      diseases and suggest further investigation into the interplay between the types I
      and II IFNs during the ontogeny of pathogenic autoantibodies.

PMID- 15265951
TI  - Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer.
AB  - The major limiting factor in the successful application of adjuvant therapy for
      metastatic disease is the lack of adjuvant specificity that leads to severe side
      effects. Reasoning that T cells of the immune system are highly specific, we
      generated tumor-specific T cells by genetic modification of mouse primary T cells
      with a chimeric receptor reactive with the human breast cancer-associated Ag erbB
      2. These T cells killed breast cancer cells and secreted IFN-gamma in an Ag
      specific manner in vitro. We investigated their use against metastatic breast
      cancer in mice in an adjuvant setting, and compared their effectiveness with the
      commonly applied adjuvants doxorubicin, 5-fluorouracil, and herceptin. Mice were
      inoculated orthotopically with the human erbB-2-expressing spontaneously
      metastatic mouse breast cancer 4T1.2 in mammary tissue, and the primary tumor was
      surgically removed 8 days later. Significant metastatic disease was demonstrated
      in lung and liver at the time of surgery on day 8 with increased tumor burden at
      later time points. T cell adjuvant treatment of day 8 metastatic disease resulted
      in dramatic increases in survival of mice, and this survival was significantly
      greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin.

PMID- 15265952
TI  - Characterization of human T cells that regulate neutrophilic skin inflammation.
AB  - It is unknown whether neutrophilic inflammations can be regulated by T cells.
      This question was analyzed by studying acute generalized exanthematous pustulosis
      (AGEP), which is a severe drug hypersensitivity resulting in intraepidermal or
      subcorneal sterile pustules. Recently, we found that drug-specific blood and skin
      T cells from AGEP patients secrete high levels of the potent neutrophil
      attracting chemokine IL-8/CXCL8. In this study, we characterize the phenotype and
      function of CXCL8-producing T cells. Supernatants from CXCL8(+) T cells were
      strongly chemotactic for neutrophils, CXCR1, and CXCR2 transfectants, but not for
      transfectants expressing CXCR4, CX3CR1, human chemokine receptor, and RDC1.
      Neutralization experiments indicated that chemotaxis was mainly mediated by
      CXCL8, but not by granulocyte chemotactic protein-2/CXCL6, epithelial cell
      derived neutrophil attractant-78/CXCL5, or growth-related oncogene
      alpha,beta,gamma/CXCL1,2,3. Interestingly, approximately 2.5% of CD4(+) T cells
      in normal peripheral blood also produced CXCL8. In addition to CXCL8, AGEP T
      cells produced large amounts of the monocyte/neutrophil-activating cytokine GM
      CSF, and the majority released IFN-gamma and the proinflammatory cytokine TNF
      alpha. Furthermore, apoptosis in neutrophils treated with conditioned medium from
      CXCL8(+) T cells could be reduced by 40%. In lesional skin, CXCL8(+) T cells
      consistently expressed the chemokine receptor CCR6, suggesting a prominent role
      for CCR6 in early inflammatory T cell recruitment. Finally, our data suggest that
      CXCL8-producing T cells facilitate skin inflammation by orchestrating
      neutrophilic infiltration and ensuring neutrophil survival, which leads to
      sterile pustular eruptions found in AGEP patients. This mechanism may be relevant
      for other T cell-mediated diseases with a neutrophilic inflammation such as
      Behcet's disease and pustular psoriasis.

PMID- 15265953
TI  - Hepatic CD1d expression in hepatitis C virus infection and recognition by
      resident proinflammatory CD1d-reactive T cells.
AB  - A subset of CD161(+)CD56(+/-) NKT cells can recognize glycolipids presented by
      CD1d and positively or negatively regulate inflammatory responses, including
      those implicated in several models of hepatitis. CD1d is expressed at very low
      levels in the healthy liver, but there is a large fraction of CD161(+)CD56(+) NKT
      cells. There are high levels of nonclassical proinflammatory hepatic CD1d
      reactive T cells in hepatitis C virus (HCV) infection. Hepatic inflammatory cells
      and biliary cells adjacent to portal tract fibrotic areas of HCV-infected donors
      specifically up-regulated CD1d. A hepatocyte cell line expressing minimal CD1d
      was efficiently recognized by hepatic CD1d-reactive T cells, suggesting a role
      for these cells in disease. Hepatic CD1d-reactive T cells from HCV-positive as
      well as negative donors produced large amounts of IFN-gamma with some IL-13, but
      only rarely detectable IL-4. We confirmed large numbers of hepatic CD161(+) T
      cells, lower levels of CD56(+) T cells, and small numbers of classic invariant
      NKT cells. However, hepatic CD1d-reactivity was not restricted to any of these
      populations. We suggest virally infected hepatic cells can process potent CD1d
      presented liver Ag(s), for surveillance by resident Th1 hepatic CD1d-reactive T
      cells. This process may be beneficial in acute viral clearance, but in chronic
      infection could contribute to liver injury.

PMID- 15265955
TI  - Increased expression and activation of CD30 induce apoptosis in human blood
      eosinophils.
AB  - Eosinophils are one of the major effector cells in asthma, and controlling the
      number and survival of eosinophils might attenuate the severity of asthma. This
      result could be achieved by inducing eosinophil apoptosis. Apoptosis allows the
      removal of cells without inducing an inflammatory response. Our knowledge of the
      factors involved in regulating eosinophil apoptosis remains limited. CD30
      molecule has been associated with T cell-negative selection and in TCR-mediated
      apoptosis. In this study we examined the expression and role of CD30 in apoptosis
      of human blood eosinophils. Percentage of apoptotic eosinophils was determined by
      annexin V-propidium iodide labeling, and CD30 expression was examined by flow
      cytometry. Spontaneous apoptosis was induced by serum deprivation, and survival
      was conferred by incubating cells with 10% FBS and IL-5. CD30 surface expression
      was up-regulated in eosinophils incubated for 24 h as compared with freshly
      isolated eosinophils, and both CD30 expression and eosinophil apoptosis increased
      in a time-dependent manner. We also measured CD30 mRNA expression by quantitative
      real-time RT-PCR and determined that CD30 transcripts increased in eosinophils
      undergoing apoptosis only under serum deprivation conditions. The agonistic CD30
      Abs, Ber-H8 and HeFi-1, significantly enhanced eosinophil apoptosis. FBS and IL-5
      failed to inhibit or suppress the CD30 agonistic-induced apoptosis. These data
      support the role of CD30 activation in eosinophil apoptosis. This research will
      help in furthering our understanding of eosinophil apoptosis and therefore might
      contribute to the development of better therapeutic modalities in the treatment
      and/or cure of allergic inflammation in bronchial asthma.

PMID- 15265954
TI  - Schistosoma mansoni and alpha-galactosylceramide: prophylactic effect of Th1
      Immune suppression in a mouse model of Graves' hyperthyroidism.
AB  - Graves' hyperthyroidism, an organ-specific autoimmune disease mediated by
      stimulatory thyrotropin receptor (TSHR) autoantibodies, has been considered a Th2
      dominant disease. However, recent data with mouse Graves' models are conflicting.
      For example, we recently demonstrated that injection of BALB/c mice with
      adenovirus coding the TSHR induced Graves' hyperthyroidism characterized by mixed
      Th1 and Th2 immune responses against the TSHR, and that transient coexpression of
      the Th2 cytokine IL-4 by adenovirus skewed Ag-specific immune response toward Th2
      and suppressed disease induction. To gain further insight into the relationship
      between immune polarization and Graves' disease, we evaluated the effect of Th2
      immune polarization by helminth Schistosoma mansoni infection and alpha
      galactosylceramide (alpha-GalCer), both known to bias the systemic immune
      response to Th2, on Graves' disease. S. mansoni infection first induced mixed Th1
      and Th2 immune responses to soluble worm Ags, followed by a Th2 response to
      soluble egg Ags. Prior infection with S. mansoni suppressed the Th1-type anti
      TSHR immune response, as demonstrated by impaired Ag-specific IFN-gamma secretion
      of splenocytes and decreased titers of IgG2a subclass anti-TSHR Abs, and also
      prevented disease development. Similarly, alpha-GalCer suppressed Ag-specific
      splenocyte secretion of IFN-gamma and prevented disease induction. However, once
      the anti-TSHR immune response was fully induced, S. mansoni or alpha-GalCer was
      ineffective in curing disease. These data support the Th1 theory in Graves'
      disease and indicate that suppression of the Th1-type immune response at the time
      of Ag priming may be crucial for inhibiting the pathogenic anti-TSHR immune
      response.

PMID- 15265956
TI  - Central memory CD4+ T cell responses in chronic HIV infection are not restored by
      antiretroviral therapy.
AB  - A strong CD4(+) T cell response has been correlated with better control of HIV
      infection. However, the effect of HIV on the maintenance of Ag-specific memory
      CD4(+) T cells is not fully understood. We characterized the function and
      phenotype of memory CD4(+) T cells generated by mumps and influenza A or B
      viruses in HIV-infected individuals receiving highly active antiretroviral
      therapy (n = 21), HIV-infected long-term nonprogressors (n = 10), and HIV
      seronegative volunteers (n = 10). We observed significantly decreased
      proliferation of the Ag-specific central memory CD4(+) T cell population
      (CD28(+)/CCR7(+)/CD45RA(-)) in the antiretroviral treated HIV-infected
      individuals compared with the seronegative controls. Restored CD4(+) T cell count
      and decreased HIV viral load while on highly active antiretroviral therapy did
      not result in increased proliferation, whereas nadir CD4(+) T cell count
      predicted the presence of Ag-specific proliferation. Our results indicate that
      HIV infection leads to impaired maintenance of virus-induced or vaccine-generated
      central memory CD4(+) T cells that is not restored by HAART.

PMID- 15265957
TI  - Monocyte activation by circulating fibronectin fragments in HIV-1-infected
      patients.
AB  - To identify signals that can alter leukocyte function in patients receiving
      highly active antiretroviral therapy (HAART), we analyzed single blood samples
      from 74 HIV-1-infected patients and additional blood was collected at 90-day
      intervals from 51 HIV-1-infected patients over a 516 +/- 172 (mean +/- SD) day
      interval. Despite the absence of circulating immune complexes and normalization
      of phagocytic function, compared with controls, the fraction of patients'
      monocytes expressing CD49e and CD62L was decreased and expression of CD11b and
      CD86 increased. Plasma from 63% of patients but none from normal controls
      contained 110-120 kDa fibronectin fragments (FNf). Presence of FNf did not
      reflect poor adherence to therapy. Addition of FNf to normal donor blood in vitro
      replicated changes in monocyte CD49e, CD62L, CD11b, and CD86 seen in vivo. FNf
      also induced monocytes to release a serine proteinase, nominally identified as
      proteinase-3, that hydrolyzed cell surface CD49e. alpha(1)-Antitrypsin blocked
      FNf-induced shedding of CD49e in a dose-dependent manner. Plasma with a normal
      frequency of CD49e(+) monocytes contained antiproteases that partially blocked
      FNf-induced monocyte CD49e shedding, whereas plasma from patients with a low
      frequency of CD49e(+) monocytes did not block this effect of FNf. Electrophoretic
      analyses of plasma from the latter group of patients suggested that a significant
      fraction of their alpha(1)-antitrypsin was tied up in high molecular mass
      complexes. These results suggest that monocyte behavior in HIV-1-infected
      patients may be influenced by FNf and the ratio of protease and antiproteases in
      the cells' microenvironment.

PMID- 15265958
TI  - Barriers to clinical trial enrollment: are state mandates the solution?

PMID- 15265959
TI  - Checking up on the surveillance, epidemiology, and end results program.

PMID- 15265960
TI  - Cervical neoplasia and highly active antiretroviral therapy.

PMID- 15265961
TI  - Early-stage lung cancer findings end a debate, put focus on next steps.

PMID- 15265962
TI  - Trial results boost circulating tumor cell field.

PMID- 15265963
TI  - Zerhouni proposes major changes to NIH ethics program.

PMID- 15265964
TI  - Where there's no smoke: popular smoke-free laws curbing active, passive smoking.

PMID- 15265965
TI  - Stat bite: Municipalities with smoke-free laws.

PMID- 15265966
TI  - FDA panel scrutinizes safety of anti-anemia drugs.

PMID- 15265967
TI  - Cancer trial enrollment after state-mandated reimbursement.
AB  - BACKGROUND: Recruitment of patients into cancer research studies is exceedingly
      difficult, particularly for early phase trials. Payer reimbursement policies are
      a frequently cited barrier. We examined whether state policies that ensure
      coverage of routine medical care costs for cancer trial participants are
      associated with an increase in clinical trial enrollment. METHODS: We used
      logistic Poisson regressions to analyze enrollment in National Cancer Institute
      phase II and phase III Clinical Trials Cooperative Group trials and compared
      changes in trial enrollment rates between 1996 and 2001 of privately insured
      cancer patients who resided in the four states that enacted coverage policies in
      1999 with enrollment rates in states without such policies. All statistical tests
      were two-sided. RESULTS: Trial enrollment rates increased in the coverage and
      noncoverage states by 24.9% (95% confidence interval [CI] = 22.8% to 27.0%) and
      28.8% (95% CI = 27.7% to 29.8%) per year, respectively, from 1996 through 2001.
      After implementation of the coverage policies in 1999 in four states, there was a
      21.7% (95% CI = 3.8% to 42.6%) annual increase in phase II trial enrollment in
      coverage states, compared with a 15.6% (95% CI = 8.8% to 21.8%) annual decrease
      in noncoverage states (P<.001). After accounting for secular trend, cancer type,
      and race in multivariable analyses, the odds ratio (OR) for a phase II trial
      participant residing in a coverage versus a noncoverage state after 1999 was 1.59
      per year (95% CI = 1.22 to 2.07; P =.001). In a multivariable analysis of phase
      III trial participation, there was a decrease in the odds of residing in a
      coverage state after 1999 (OR = 0.90, 95% CI = 0.84 to 0.98; P =.011).
      CONCLUSION: State coverage policies were associated with a statistically
      significant increase in phase II cancer trial participation and did not increase
      phase III cancer trial enrollment.

PMID- 15265968
TI  - Highly active antiretroviral therapy and cervical squamous intraepithelial
      lesions in human immunodeficiency virus-positive women.
AB  - BACKGROUND: Women infected with human immunodeficiency virus (HIV) have an
      increased risk of persistent squamous intraepithelial lesions (SILs) of the
      cervix. We assessed the association between use of highly active antiretroviral
      therapy (HAART) and regression of SIL in HIV-infected women enrolled in the
      Women's Interagency HIV Study, a large, multicenter, prospective cohort study.
      METHODS: Of 2059 HIV-infected participants, 312 HIV-infected women had normal
      cervical cytology at baseline and were subsequently diagnosed during 7 years of
      follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information
      regarding use of HAART were obtained every 6 months. The outcome of interest was
      lesion regression, defined as two consecutive normal Pap smears 6 months apart.
      Incidence rates of SIL regression were computed among person-years at risk, both
      before and after HAART initiation. All statistical tests were two-sided. RESULTS:
      Of 312 women, 141 had lesions that regressed to normal cytology, with a median
      time to regression of 2.7 years. Overall, the incidence of regression increased
      (P(trend) =.002) over time after HAART was introduced. At incident SIL, median
      CD4+ T-cell counts were lower in women whose lesions did not regress than in
      women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART
      was introduced, the rate of lesion regression was 0.0% (95% confidence interval
      [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI =
      9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002).
      CONCLUSIONS: HAART use was associated with increased regression of SIL among HIV
      infected women, and among women who used HAART, increased CD4+ T-cell counts were
      associated with a greater likelihood of regression. However, the majority of
      cervical lesions among HIV-infected women, even among individuals who used HAART,
      did not regress to normal.

PMID- 15265970
TI  - Quality of life and trial adherence among participants in the prostate, lung,
      colorectal, and ovarian cancer screening trial.
AB  - BACKGROUND: The National Cancer Institute's Prostate, Lung, Colorectal, and
      Ovarian (PLCO) Cancer Screening Trial was designed to examine whether annual
      screening tests for these four tumor sites result in reduced disease-related
      mortality. We assessed the impact of trial participation on both health-related
      quality of life (HRQL) and trial adherence. METHODS: Participants (N = 432; 217
      in the control arm and 215 in screening arm) were accrued from the Georgetown
      University PLCO site from May through December 1998. Screening-arm participants
      were interviewed by telephone at baseline (prescreening), shortly after
      notification of screening results (short-term follow-up), and 9 months after
      notification of screening results (intermediate-term follow up). Control-arm
      participants completed a baseline and 1-year follow-up assessment. Logistic
      regression analyses were conducted. RESULTS: Participants reported high levels of
      HRQL and satisfaction with their decision to participate. Screening-arm
      participants with abnormal screening results had a higher level of intrusive
      thoughts about cancer than those with all normal results (odds ratio [OR] = 2.9,
      95% confidence interval [CI] = 1.3 to 6.3) at the short-term follow-up but not at
      the intermediate-term follow-up (when abnormal test results were known to be
      false positive; OR = 1.9, 95% CI = 0.89 to 4.2). Trial adherence was
      statistically significantly better among participants who had received all normal
      results in the previous year's screening tests (93.7% versus 78.7%; OR = 3.7, CI
      = 1.1 to 12.0) than in those who received at least one abnormal result. In the
      control arm, adherence (defined as returning annual questionnaires) was
      positively associated with education (OR = 3.4, 95% CI = 1.4 to 8.4) and sex,
      with women being more likely to return questionnaires than men (OR = 2.1, 95% CI
      = 1.05 to 4.4). CONCLUSIONS: It is feasible to collect HRQL measures as part of a
      large cancer screening trial. Prior abnormal screening results were related to
      short-term HRQL but not to intermediate-term HRQL. Trial adherence was poorer
      among those who had received previous false-positive results. These results
      suggest several methods for improving adherence in this and other subgroups.

PMID- 15265969
TI  - Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high
      dose, late-intensification chemotherapy in high-risk breast cancer patients: a
      randomized trial.
AB  - BACKGROUND: Breast cancer patients with four or more positive axillary lymph
      nodes who are treated with conventional adjuvant therapy have a poor prognosis.
      In uncontrolled studies, high-dose chemotherapy produced much better results than
      conventional therapy. We compared the benefits of a single cycle of high-dose
      chemotherapy and the benefits of conventional chemotherapy in patients with high
      risk breast cancer in a prospective, unblinded, randomized trial. METHODS:
      Between February 23, 1995, and June 29, 1999, 605 patients with breast cancer who
      had four or more positive lymph nodes were randomly assigned to treatment (307 to
      high-dose therapy and 298 to conventional therapy). The conventional chemotherapy
      regimen was four cycles of doxorubicin (75 mg/m2) followed by eight cycles of CMF
      (cyclophosphamide [600 mg/m2], methotrexate [50 mg/m2], and 5-fluorouracil [600
      mg/m2]), all given intravenously on day 1 of a 21-day cycle. The high-dose
      regimen was four cycles of doxorubicin (75 mg/m2), followed by a single cycle of
      intermediate-dose cyclophosphamide (4000 mg/m2) supported by filgrastim (300
      microg/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m2)
      and thiotepa (800 mg/m2). Peripheral blood progenitor cells were harvested by
      leukapheresis after treatment with cyclophosphamide and filgrastim and then re
      infused after the high-dose cycle. Log-rank tests were used to compare survival
      rates. All statistical analyses were two-sided. RESULTS: At a median follow-up of
      6 years, no statistically significant differences were detected between the arms
      in 5-year relapse-free survival (high-dose arm = 57%, 95% confidence interval
      [CI] = 51% to 63%; conventional-dose arm = 54%, 95% CI = 48% to 61% (P =.73) or
      in 5-year overall survival (high-dose arm = 62%, 95% CI = 56% to 68%;
      conventional-dose arm = 64%, 95% CI = 57% to 70%) (P =.38). CONCLUSION: Autograft
      supported, high-dose therapy is not superior to conventional chemotherapy in
      patients with breast cancer who have multiple involved lymph nodes. This
      conclusion should be viewed in the context of improving the success of
      conventional chemotherapy.

PMID- 15265971
TI  - Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation
      carriers.
AB  - BACKGROUND: Several studies have reported that the risk of breast cancer
      decreases with increasing duration of breast-feeding. Whether breast-feeding is
      associated with a reduced risk of hereditary breast cancer in women who carry
      deleterious BRCA1 and BRCA2 mutations is currently unknown. METHODS: We conducted
      a case-control study of women with deleterious mutations in either the BRCA1 or
      the BRCA2 gene. Study participants, drawn from an international cohort, were
      matched on the basis of BRCA mutation (BRCA1 [n = 685] or BRCA2 [n = 280]), year
      of birth (+/-2 years), and country of residence. The study involved 965 case
      subjects diagnosed with breast cancer and 965 control subjects who had no history
      of breast or ovarian cancer. Information on pregnancies and breast-feeding
      practices was derived from a questionnaire administered to the women during the
      course of genetic counseling. Conditional logistic regression analyses were used
      to estimate odds ratios (ORs) for the risk of breast cancer. All statistical
      tests were two-sided. RESULTS: Among women with BRCA1 mutations, the mean total
      duration of breast-feeding was statistically significantly shorter for case
      subjects than for control subjects (6.0 versus 8.7 months, respectively; mean
      difference = 2.7 months, 95% confidence interval [CI] = 1.4 to 4.0; P<.001). The
      total duration of breast-feeding was associated with a reduced risk of breast
      cancer (for each month of breast-feeding, OR = 0.98, 95% CI = 0.97 to 0.99;
      P(trend)<.001). Women with BRCA1 mutations who breast-fed for more than 1 year
      were less likely to have breast cancer than those who never breast-fed (OR =
      0.55, 95% CI = 0.38 to 0.80; P =.001), although no such association was seen for
      BRCA2 (OR = 0.95, 95% CI = 0.56 to 1.59; P =.83). CONCLUSIONS: Women with
      deleterious BRCA1 mutations who breast-fed for a cumulative total of more than 1
      year had a statistically significantly reduced risk of breast cancer.

PMID- 15265972
TI  - Electrospray ionization-tandem mass spectrometry and 32P-postlabeling analyses of
      tamoxifen-DNA adducts in humans.
AB  - BACKGROUND: Although the nonsteroidal antiestrogen tamoxifen is used as an
      adjuvant chemotherapeutic agent to treat hormone-dependent breast cancer and as a
      chemopreventive agent in women with elevated risk of breast cancer, it has also
      been reported to increase the risk of endometrial cancer. Reports of low levels
      of tamoxifen-DNA adducts in human endometrial tissue have suggested that
      tamoxifen induces endometrial cancer by a genotoxic mechanism. However, these
      findings have been controversial. We used electrospray ionization-tandem mass
      spectrometry (ES-MS/MS) and 32P-postlabeling analyses to investigate the presence
      of tamoxifen-DNA adducts in human endometrial tissue. METHODS: Endometrial DNA
      from eight tamoxifen-treated women and eight untreated women was hydrolyzed to
      nucleosides and assayed for (E)-alpha-(deoxyguanosin-N2-yl)-tamoxifen (dG-Tam)
      and (E)-alpha-(deoxyguanosin-N2-yl)-N-desmethyltamoxifen (dG-desMeTam), the two
      major tamoxifen-DNA adducts that have been reported to be present in humans
      and/or experimental animals treated with tamoxifen, using on-line sample
      preparation coupled with high-performance liquid chromatography (HPLC) and ES
      MS/MS. The same DNA samples were assayed for the presence of dG-Tam and dG
      desMeTam by (32)P-postlabeling methodology, using two different DNA digestion and
      labeling protocols, followed by both thin-layer chromatography and HPLC. RESULTS:
      We did not detect either tamoxifen-DNA adduct by HPLC-ES-MS/MS analyses (limits
      of detection for dG-Tam and dG-desMeTam were two adducts per 10(9) nucleotides
      and two adducts per 10(8) nucleotides, respectively) or by 32P-postlabeling
      analyses (limit of detection for both adducts was one adduct per 10(9)
      nucleotides) in any of the endometrial DNA samples. CONCLUSION: The initiation of
      endometrial cancer by tamoxifen is probably not due to a genotoxic mechanism
      involving the formation of dG-Tam or dG-desMeTam.

PMID- 15265973
TI  - Lung cancer histologic type in the surveillance, epidemiology, and end results
      registry versus independent review.
AB  - Because few studies have assessed the accuracy of lung cancer histologic
      diagnoses reported by state cancer registries, we examined whether the Iowa
      Surveillance, Epidemiology, and End Results Cancer Registry (i.e., the Iowa
      Cancer Registry)-reported lung cancer histologic diagnoses were reliable. We
      investigated agreement between lung cancer histologic types reported for 413
      patients with lung cancer by the Iowa Cancer Registry and those obtained through
      an independent review of diagnostic slides. Among lung cancer histologic types,
      small-cell carcinoma had the highest sensitivity (94.1%, 95% confidence interval
      [CI] = 85.6% to 98.4%), positive predictive value (94.1%, 95% CI = 85.6% to
      98.4%), negative predictive value (98.8%, 95% CI = 96.9% to 99.7%), and highest
      percent exact agreement (98.0%, 95% CI = 96.6% to 99.4%). The lowest sensitivity
      (21.9%, 95% CI = 9.3% to 40.0%) and positive predictive value (23.3%, 95% CI =
      9.9% to 42.3%) were noted for large-cell carcinoma, probably because other more
      specific features of adenocarcinoma or squamous carcinoma were absent.
      Adenocarcinoma had the lowest specificity (84.4%, 95% CI = 79.0% to 88.9%),
      negative predictive value (85.2%, 95% CI = 79.9% to 89.6%), and percent exact
      agreement (82.9%, 95% CI = 79.2% to 86.6%). Samples collected by cytologic
      examination (odds ratio [OR] = 2.4, 95% CI = 1.1 to 5.2) or biopsy examination
      (OR = 2.2, 95% CI = 1.1 to 4.2) were more likely to be misclassified than samples
      obtained via resection. Thus, the histologic type obtained by the Iowa Cancer
      Registry is reasonably reliable, but independent slide review is needed for
      precise histologic typing of lung cancer.

PMID- 15265974
TI  - Re: Zinc supplement use and risk of prostate cancer.

PMID- 15265975
TI  - Re: National Institutes of Health State-of-the-Science Conference Statement:
      Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002.

PMID- 15265976
TI  - Re: Trends in the treatment of ductal carcinoma in situ of the breast.

PMID- 15265977
TI  - Re: Breast-conserving surgery with or without radiotherapy: pooled-analysis for
      risks of ipsilateral breast tumor recurrence and mortality.

PMID- 15265978
TI  - Submandibular gland acinar cells express multiple alpha1-adrenoceptor subtypes.
AB  - We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands
      as a possible model for alpha(1)-adrenoceptor regulation of submandibular
      function. alpha(1)-Adrenoceptors are subdivided into three subtypes called
      alpha(1A), alpha(1B), and alpha(1D), which can be distinguished from one another
      by their differential affinity values for subtype-selective alpha(1)-adrenoceptor
      antagonists. Thus, alpha(1)-adrenoceptor subtypes in SMG-C10 cells were
      characterized with reverse transcription-polymerase chain reaction (RT-PCR) and
      [(3)H]prazosin binding in side-by-side experiments with native submandibular
      glands. RT-PCR identified mRNAs for alpha(1A)-, alpha(1B)-, and alpha(1D)
      adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of
      [(3)H]prazosin binding by 5-methylurapidil (alpha(1A)-selective) was biphasic and
      fit best to a two-site binding model with 40 +/- 8% high (K(iH))- and 60 +/- 10%
      low (K(iL))-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low
      affinity binding sites in submandibular glands. Respective K(iH) and K(iL) values
      for 5-methylurapidil were 1.9 +/- 0.4 and 100 +/- 30 nM in SMG-C10 cells and 3.2
      +/- 0.8 and 170 +/- 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione
      dihydrochloride (alpha(1D)-selective)] bound with low affinity in SMG-C10 cells
      and submandibular glands with K(i) values of 81 +/- 20 and 110 +/- 20 nM,
      respectively. Chloroethylclondine, an irreversible alkylating agent selective for
      alpha(1B) adrenoceptors, reduced the density of [(3)H]prazosin binding sites by
      42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10
      cells and submandibular glands are similar in expressing receptor protein for
      alpha(1A)- and alpha(1B)-adrenoceptor subtypes, establishing SMG-C10 cells as a
      potential model for alpha(1)-adrenoceptor-mediated secretion.

PMID- 15265979
TI  - Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is
      associated with peroxisome proliferator-activated receptor-alpha target gene
      activation.
AB  - Amiodarone, an efficacious and widely used antiarrhythmic agent, has been
      reported to cause hepatotoxicity in some patients. To gain insight into the
      mechanism of this unwanted effect, mice were administered various doses of
      amiodarone and examined for changes in hepatic histology and gene regulation.
      Amiodarone induced hepatomegaly, hepatocyte microvesicular lipid accumulation,
      and a significant decrease in serum triglycerides and glucose. Northern blot
      analysis of hepatic RNA revealed a dose-dependent increase in the expression of a
      number of genes critical for fatty acid oxidation, lipoprotein assembly, and
      lipid transport. Many of these genes are regulated by the peroxisome proliferator
      activated receptor-alpha (PPARalpha), a ligand-activated nuclear hormone receptor
      transcription factor. The absence of induction of these genes as well as
      hepatomegaly in PPARalpha knockout [PPARalpha-/-] mice indicated that the effects
      of amiodarone were dependent upon the presence of a functional PPARalpha gene.
      Compared to wild-type mice, treatment of PPARalpha-/- mice with amiodarone
      resulted in an increased rate and extent of total body weight loss. The inability
      of amiodarone to directly activate either human or mouse PPARalpha transiently
      expressed in human HepG2 hepatoma cells indicates that the effects of amiodarone
      on the function of this receptor were indirect. Based upon these results, we
      conclude that amiodarone disrupts hepatic lipid homeostasis and that the
      increased expression of PPARalpha target genes is secondary to this toxic effect.
      These results provide important new mechanistic information regarding the
      hepatotoxic effects of amiodarone and indicate that PPARalpha protects against
      amiodarone-induced hepatotoxicity.

PMID- 15265980
TI  - DNA replication and transcription direct a DNA strand bias in the process of
      targeted gene repair in mammalian cells.
AB  - The repair of point mutations can be directed by modified single-stranded DNA
      oligonucleotides and regulated by cellular activities including homologous
      recombination, mismatch repair and transcription. Now, we report that DNA
      replication modulates the gene repair process by influencing the frequency with
      which either DNA strand is corrected. An SV40-virus-based system was used to
      investigate the role of DNA synthesis on gene repair in COS-1 cells. We confirm
      that transcription exerts a strand bias on the gene repair process even when
      correction takes place on actively replicating templates. We were able to
      distinguish between the influences of transcription and replication on strand
      bias by changing the orientation of a gene encoding enhanced green fluorescent
      protein relative to the origin of replication, and confirmed the previously
      observed bias towards the untranscribed strand. We report that DNA replication
      can increase the level of untranscribed strand preference only if that strand
      also serves as the lagging strand in DNA synthesis. Furthermore, the effect of
      replication on gene repair frequency and strand bias appears to be independent of
      certain mismatched base pairs and oligonucleotide length.

PMID- 15265981
TI  - Integrin alpha3beta1 directs the stabilization of a polarized lamellipodium in
      epithelial cells through activation of Rac1.
AB  - Epithelial cell migration is a crucial event in wound healing, yet little is
      known about mechanisms whereby integrins regulate epithelial cell polarization
      and migration. In the present work, we demonstrate the importance of adhesion
      through the alpha3beta1 integrin in promoting the stabilization of leading
      lamellipodia in migrating keratinocytes. We demonstrate that this integrin is
      found at the leading edge of migrating keratinocytes and that inhibition of
      alpha3beta1 binding to laminin-5 prevents the formation of stable leading
      lamellipodia. Consistent with this observation, keratinocytes derived from
      alpha3beta1-deficient mice fail to form stable leading lamellipodia but retain
      the ability to form actin-containing protrusions that rapidly extend and retract
      from the cell membrane. Formation of a leading lamellipodium also requires
      alpha3beta1-dependent activation of Rac1, because alpha3beta1-deficient
      keratinocytes show decreased activation of Rac1 compared with alpha3beta1
      expressing cells, and formation of stable leading lamellipodia can be inhibited
      in the latter cells by expression of the dominant negative Rac1 mutant Rac1N17.
      Furthermore, alpha3beta1-deficient keratinocytes expressing constitutively active
      Rac1L61 failed to form stable lamellipodia when plated onto laminin-5,
      demonstrating that alpha3beta1 is required for Rac1-mediated formation of a
      stable lamellipodium. These observations identify a crucial role for integrin
      mediated adhesion and signaling in the formation of large, polarized, stable
      lamellipodia by migrating epithelial cells. To our knowledge, this study is the
      first to demonstrate that signal transduction through a specific integrin is
      required to direct the development of a lamellipodium from an initial protrusion
      and promote persistent epithelial cell migration.

PMID- 15265982
TI  - Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO
      inhibits neurite outgrowth from cerebellar granule cells.
AB  - IgLONs are a family of four cell adhesion molecules belonging to the Ig
      superfamily that are thought to play a role in cell-cell recognition and growth
      cone migration. One member of the family, opioid-binding cell-adhesion molecule
      (OBCAM), might act as a tumour suppressor. Previous work has shown that limbic
      system-associated protein (LAMP), CEPU-1/Neurotrimin and OBCAM interact
      homophilically and heterophilically within the family. Here, we show that, based
      on their relative affinities, CEPU-1 might be both a homo- and a heterophilic
      cell adhesion molecule, whereas LAMP and OBCAM act only as heterophilic cell
      adhesion molecules. A binding assay using recombinant IgLONs fused to human Fc
      showed that IgLONs are organized in the plane of the membrane as heterodimers,
      and we propose that IgLONs function predominantly as subunits of heterodimeric
      proteins (Diglons). Thus, the four IgLONs can form six Diglons. Furthermore,
      although singly transfected cell lines have little effect on neurite outgrowth,
      CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite
      outgrowth from cerebellar granule cells.

PMID- 15265983
TI  - pRb, Myc and p53 are critically involved in SV40 large T antigen repression of
      PDGF beta-receptor transcription.
AB  - The expression of the PDGF beta-receptor is tightly regulated during a normal
      cell cycle. c-Myc and p73alpha repress transcription of the receptor through
      interaction with NF-Y. In ST15A cells which stably express the temperature
      sensitive SV40 large T antigen (LT) the receptor expression and ligand binding
      decreased under the permissive condition. Transient expression of the LT, but not
      small t, decreased the endogenous receptor expression at mRNA and protein levels
      in NIH3T3 cells but not in the myc-null HO15.19 cells. The wild-type LT, but not
      the various pRb or p53 binding defective LT mutants, represses the PDGF beta
      receptor promoter activity. Moreover, the inability of the LT-mediated repression
      in the myc-null cells, the Rb-null 3T3 cells, and the Saos-2 cells lacking pRb
      and p53, indicates that Myc, pRb and p53 are all necessary elements. PDGF beta
      receptor promoter-luciferase assays revealed that the CCAAT motif is important
      for the repression. Furthermore, p53 was found to increase the promoter activity
      mainly via the upstream Sp1 binding sites together with the CCAAT motif in the
      NIH 3T3 cells. This was confirmed by Schneider's Drosophila line (SL2) cells
      deficient in both endogenous NF-Y and Sp1. Chromatin immunoprecipitation using
      ST15A cells revealed that both LT and p53 bound the PDGF beta-receptor promoter
      and the binding of p53 diminished when LT was expressed in the permissive
      condition. However, LT binds the promoter in the absence of pRb and p53 in Saos-2
      cells stably expressing LT. These results suggest that LT binds the promoter and
      interferes with NF-Y and Sp1 to repress it in the presence of Myc, pRb and p53.

PMID- 15265984
TI  - Continuous phosphatidylinositol metabolism is required for cleavage of crane fly
      spermatocytes.
AB  - Successful cleavage of animal cells requires co-ordinated regulation of the
      actomyosin contractile ring and cleavage furrow ingression. Data from a variety
      of systems implicate phosphoinositol lipids and calcium release as potential
      regulators of this fundamental process. Here we examine the requirement for
      various steps of the phosphatidylinositol (PtdIns) cycle in dividing crane fly
      (Nephrotoma suturalis) spermatocytes. PtdIns cycle inhibitors were added to
      living cells after cleavage furrows formed and began to ingress. Inhibitors known
      to block PtdIns recycling (lithium), PtdIns phosphorylation (wortmannin,
      LY294002) or phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] hydrolysis
      [U73122 (U7)] all stopped or slowed furrowing. The effect of these drugs on
      cytokinesis was quite rapid (within 0-4 minutes), so continuous metabolism of
      PtdIns appears to be required for continued cleavage furrow ingression. U7 caused
      cleavage furrow regression concomitant with depletion of F-actin from the
      contractile ring, whereas the other inhibitors caused neither regression nor
      depletion of F-actin. That U7 depletes furrow-associated actin seems
      counterintuitive, as inhibition of phospholipase C would be expected to increase
      cellular levels of PtdIns(4,5)P(2) and hence increase actin polymerization. Our
      confocal images suggest, however, that F-actin might accumulate at the poles of
      U7-treated cells, consistent with the idea that PtdIns(4,5)P(2) hydrolysis may be
      required for actin filaments formed at the poles to participate in contractile
      ring assembly at the furrow.

PMID- 15265985
TI  - The yeast dynamin-related GTPase Vps1p functions in the organization of the actin
      cytoskeleton via interaction with Sla1p.
AB  - Recent studies have suggested that the function of the large GTPase dynamin in
      endocytosis in mammalian cells may comprise a modulation of actin cytoskeleton.
      The role of dynamin in actin cytoskeleton organization in the yeast Saccharomyces
      cerevisiae has remained undefined. In this report, we found that one of the yeast
      dynamin-related proteins, Vps1p, is required for normal actin cytoskeleton
      organization. At both permissive and non-permissive temperatures, the vps1
      mutants exhibited various degrees of phenotypes commonly associated with actin
      cytoskeleton defects: depolarized and aggregated actin structures,
      hypersensitivity to the actin cytoskeleton toxin latrunculin-A, randomized bud
      site selection and chitin deposition, and impaired efficiency in the
      internalization of membrane receptors. Over-expression of the GTPase mutants of
      vps1 also led to actin abnormalities. Consistent with these actin-related
      defects, Vps1p was found to interact physically, and partially co-localize, with
      the actin-regulatory protein Sla1p. The normal cellular localization of Sla1p
      required Vps1p and could be altered by over-expression of a region of Vps1p that
      was involved in the interaction with Sla1p. The same region also promoted mis
      sorting of the vacuolar protein carboxypeptidase Y upon over-expression. These
      findings suggest that the functions of the dynamin-related protein Vps1p in actin
      cytoskeleton dynamics and vacuolar protein sorting are probably related to each
      other.

PMID- 15265986
TI  - The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to
      minor perturbation of the cell division machinery in Schizosaccharomyces pombe.
AB  - Fission yeast mutants defective in actomyosin ring formation and function exhibit
      a prolonged G2 delay following cytokinesis failure. This G2 delay depends on the
      SIN, a signaling network essential for cytokinesis, and the non-essential Cdc14p
      family phosphatase, Clp1p/Flp1p and has been proposed to signify a cytokinesis
      checkpoint mechanism. However, the physiological relevance of this proposed
      Clp1p/Flp1p-dependent checkpoint is unclear because all previous studies were
      carried out using mutations in essential actomyosin ring components under fully
      restrictive conditions and thus these cells would have died regardless of the
      presence of the checkpoint. Here we show that delays in cytokinesis caused by
      minor perturbations to different components of the cytokinetic machinery, which
      normally cause only mild defects, become lethal when Clp1p/Flp1p is inactivated.
      In addition, we show that Clp1p/Flp1p does not function simply to inhibit further
      rounds of nuclear division, but also allows damaged actomyosin rings to be
      maintained to facilitate completion of cell division. Ectopic activation of the
      SIN significantly bypasses the requirement of Clp1p/Flp1p for G2 delay as well as
      for completion of cytokinesis. We conclude that the Clp1p/Flp1p-dependent
      cytokinesis checkpoint provides a previously unrecognized cell survival advantage
      when the cell division apparatus is mildly perturbed.

PMID- 15265987
TI  - Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that
      mediate cytoskeleton remodeling in human renal carcinoma-derived cells.
AB  - Shiga toxin is a bacterial toxin consisting of A and B subunits. Generally, the
      essential cytotoxicity of the toxin is thought to be mediated by the A subunit,
      which possesses RNA cleavage activity and thus induces protein synthesis
      inhibition. We previously reported, however, that the binding of the Shiga toxin
      1-B subunit to globotriaosyl ceramide, a functional receptor for Shiga toxin,
      induces intracellular signals in a manner that is dependent on glycolipid
      enriched membrane domains, or lipid rafts. Although the precise role of this
      signaling mechanism is not known, here we report that Shiga-toxin-mediated
      intracellular signals induce cytoskeleton remodeling in ACHN cells derived from
      renal tubular epithelial carcinoma. Using confocal laser scanning microscopy, we
      observed that Shiga toxin 1-B treatment induces morphological changes in ACHN
      cells in a time-dependent manner. In addition, the morphological changes were
      accompanied by the redistribution of a number of proteins, including actin,
      ezrin, CD44, vimentin, cytokeratin, paxillin, FAK, and alpha- and gamma-tubulins,
      all of which are involved in cytoskeletal organization. The transient
      phosphorylation of ezrin and paxillin was also observed during the course of
      protein redistribution. Experiments using inhibitors for a variety of kinases
      suggested the involvement of lipid rafts, Src family protein kinase, PI 3-kinase,
      and RHO-associated kinase in Shiga toxin 1-B-induced ezrin phosphorylation. Shiga
      toxin 1-B-induced cytoskeletal remodeling should provide an in vitro model that
      can be used to increase our understanding of the pathogenesis of Shiga-toxin
      mediated cell injury and the role of lipid-raft-mediated cell signaling in
      cytoskeletal remodeling.

PMID- 15265988
TI  - Analysis of Chlamydia caviae entry sites and involvement of Cdc42 and Rac
      activity.
AB  - In epithelial cells, endocytic activity is mostly dedicated to nutrient and
      macromolecule uptake. To invade these cells, Chlamydiaceae, like other pathogens,
      have evolved strategies that utilise the existing endocytic machineries and
      signalling pathways, but little is known about the host cell molecules involved.
      In this report, we show that within five minutes of infection of HeLa cells by
      Chlamydia caviae GPIC strain several events take place in the immediate vicinity
      of invasive bacteria: GM1-containing microdomains cluster, tyrosine
      phosphorylated proteins accumulate, and intense actin polymerization occurs. We
      show that actin polymerization is controlled by the small GTPases Cdc42 and Rac,
      which become activated upon infection. Expression of dominant negative forms of
      these GTPases inhibits C. caviae entry and leads to abnormal actin
      polymerization. In contrast, the small GTPase Rho does not seem essential for
      bacterial entry. Finally, phosphatidylinositol 3-kinase activity is also required
      for internalization of C. caviae, probably downstream of the other molecular
      events reported here. We present the first scheme of the events occurring at the
      sites of invasion of epithelial cells by a member of the Chlamydiaceae family.

PMID- 15265989
TI  - Activation of the pheromone-responsive MAP kinase drives haploid cells to undergo
      ectopic meiosis with normal telomere clustering and sister chromatid segregation
      in fission yeast.
AB  - Meiosis is a process of importance for sexually reproducing eukaryotic organisms.
      In the fission yeast Schizosaccharomyces pombe, meiosis normally proceeds in a
      diploid zygote which is produced by conjugation of haploid cells of opposite
      mating types. We demonstrate that activation of the pheromone-responsive MAPK,
      Spk1, by the ectopic expression of a constitutively active form of Byr1 (MAPKK
      for Spk1) induced the cells to undergo meiosis while in the haploid state.
      Moreover, the induction of meiosis required Mei2 (a key positive regulator of
      meiosis), but did not require Mei3; Mei3 is normally required to inactivate the
      Pat1 kinase (a negative regulator of Mei2) thereby allowing Mei2 to drive
      meiosis. Therefore, expression of a constitutively active form of Byr1 activates
      Mei2 without the need of Mei3. In cells induced to undergo meiosis by activating
      the Spk1 MAPK signaling pathway, telomeres clustered at the spindle pole body
      (SPB) and centromeres detached normally from the SPB during meiotic prophase, and
      the cells showed the correct segregation of sister chromatids during meiotic
      divisions. In contrast, in meiosis induced by inactivation of Pat1, sister
      chromatids segregate precociously during the first meiotic division. Thus, these
      results suggest that activation of Spk1 drives meiosis in S. pombe.

PMID- 15265991
TI  - Revisional hallux abducto valgus surgery using tricorrectional bunionectomy.
AB  - We present a radiographic analysis of 91 failed hallux abducto valgus surgeries.
      Patients were categorized by type of postoperative complication: hallux varus,
      hallux limitus, or recurrent hallux abducto valgus deformities. All deformities
      were radiographically evaluated preoperatively and after correction using
      tricorrectional bunionectomy. Analysis of the surgical revisions showed
      improvement in radiographic parameters, including the intermetatarsal angle,
      hallux abductus angle, proximal articular set angle, and tibial sesamoid
      position. We conclude that tricorrectional bunionectomy is a versatile procedure
      that can be used when addressing a residual deformity after failed hallux abducto
      valgus surgery.

PMID- 15265990
TI  - Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2).
AB  - The telomeric repeat binding factor 2 (TRF2) specifically recognizes TTAGGG
      tandem repeats at chromosomal ends. Unexpectedly immunofluorescence studies
      revealed a prominent nucleolar localization of TRF2 in human cells, which
      appeared as discrete dots with sizes similar to those present in the nucleoplasm.
      The TRF2 dots did not overlap with dots stemming from the upstream binding factor
      (UBF) or the B23 protein. After treatment with a low concentration of actinomycin
      D (0.05 microg/ml), TRF2 remained in the nucleolus, although this condition
      selectively inhibited RNA polymerase I and led to a relocalization of UBF and
      B23. TRF2 was prominent in the nucleolus at G0 and S but seemed to diffuse out of
      the nucleolus in G2 phase. During mitosis TRF2 dispersed from the condensed
      chromosomes and returned to the nucleolus at cytokinesis. Treatment with low
      doses of actinomycin D delayed the release of TRF2 from the nucleolus as cells
      progressed from G2 phase into mitosis. With actinomycin D present TRF2 was
      detected in discrete foci adjacent to UBF in prophase, while in metaphase a
      complete overlap between TRF2 and UBF was observed. TRF2 was present in DNase
      insensitive complexes of nucleolar extracts, whereas DNA degradation disrupted
      the protein-DNA complexes consisting of Ku antigen and B23. Following treatment
      with actinomycin D some of the mitotic cells displayed chromosome end-to-end
      fusions. This could be correlated to the actinomycin D-suppressed relocalization
      of TRF2 from the nucleolus to the telomeres during mitosis. These results support
      the view that the nucleolus may sequester TRF2 and thereby influences its
      telomeric functions.

PMID- 15265992
TI  - Morphofunctional study of brachymetatarsia of the fourth metatarsal.
AB  - Brachymetatarsia is abnormal anatomical shortness of the metatarsals. We describe
      a new diagnostic test that enables quantification of the shortening of the fourth
      metatarsal in brachymetatarsia. The metatarsodigital alterations most frequently
      related to this deformity are presented.

PMID- 15265993
TI  - Use of a maggot motility index to evaluate survival of therapeutic larvae.
AB  - Maggot debridement therapy is rapidly increasing in popularity at major diabetic
      foot and wound care centers worldwide. However, we are unaware of specific
      guidelines on the short-term storage of larvae. We sought to evaluate differences
      in maggot motility over time in larvae refrigerated versus those stored at room
      temperature. We also introduce a simple surrogate method for evaluating maggot
      vitality that may be useful for in vivo studies if validated in future works. We
      randomly selected ten larvae from the same shipment at ten different times in 9
      days. Larvae were placed on a translucent acetate grid, and their total excursion
      in 30 sec was measured. This was converted into a Maggot Motility Index. In the
      refrigerated group, the index remained at or above 40 mm/min for approximately 60
      hours from baseline, when there was a significant decrease. This same phenomenon
      occurred during the first 12 hours in the nonrefrigerated group. There were
      significant differences in motility between refrigerated and nonrefrigerated
      larvae immediately after baseline until day 8. Larvae are more practical for
      repeated clinical use if kept refrigerated between applications.

PMID- 15265994
TI  - Scanning electron microscope imaging of onychomycosis.
AB  - Although scanning electron microscope technology has been used for more than 60
      years in many fields of medical research, no studies have focused on obtaining
      high-resolution microscopic images of onychomycosis of the toenail caused by
      Trichophyton rubrum in a geriatric population. To provide new insight into the
      intricate structure and behavior of chronic toenail onychomycosis, we produced
      three-dimensional images of onychomycosis obtained from two geriatric patients
      with confirmed growth of T rubrum. The photomicrographs illustrate the pervasive
      integration and penetration of the fungus hyphal elements, underscoring the
      clinical difficulty of obtaining rapid treatment of fungal infections in the
      distal and lateral subungual space of the human toenail. Although the scanning
      electron microscope may not be a practical diagnostic tool for most physicians,
      it remains invaluable for the researcher to obtain insight into the spatial
      orientation, behavior, and appearance of onychomycosis.

PMID- 15265995
TI  - A patient satisfaction survey on prescription custom-molded foot orthoses.
AB  - A survey of patients treated at the Foot and Ankle Institute at the Temple
      University School of Podiatric Medicine in Philadelphia, Pennsylvania, was
      conducted regarding their satisfaction with thermoplastic prescription foot
      orthoses. Two hundred seventy-five completed questionnaires from patients who had
      had their orthoses for 1 year or more were analyzed. Overall, the majority of
      respondents indicated that they were satisfied with their devices, obtaining
      significant (60% to 100%) relief of symptoms. Very few patients indicated total
      dissatisfaction; only 9% reported 0% relief of their symptoms. The data strongly
      suggest that custom-molded foot orthoses are an effective and viable treatment
      modality associated with a high level of patient satisfaction.

PMID- 15265996
TI  - Combined popliteal and saphenous nerve blocks at the knee: an underused
      alternative to general or spinal anesthesia for foot and ankle surgery.
AB  - Peripheral nerve blocks at the ankle have long been used for foot surgery.
      However, when local foot and ankle blocks are inappropriate or contraindicated,
      general and spinal anesthesia are the common alternatives. Both have
      disadvantages and require added equipment and monitors. Combined popliteal and
      saphenous nerve blocks at the knee can offer a desirable alternative to general
      and spinal anesthesia for foot and ankle surgery. In addition, popliteal and
      saphenous nerve blocks provide anesthesia of the entire lower leg, thus
      permitting a greater variety of procedures to be performed. This article reviews
      the anatomical considerations, various block techniques, and surgical
      applications of this useful approach to lower-leg anesthesia.

PMID- 15265997
TI  - A survey of podiatric medical students' computer literacy.
AB  - This article reviews the extent of health-care students' computer literacy and
      presents the results of a survey of podiatric medical students' computer
      literacy. The results of this survey indicate that podiatric medical students are
      more likely than other health-care students to rate their computer literacy as
      good or very good. There was no gender difference in this self-reported computer
      knowledge. The implications for designing and using Web-based instructional
      materials and technology for podiatric medical students are discussed.

PMID- 15265998
TI  - Complications of intra-articular fractures of the calcaneus.
AB  - Most complications of calcaneal fractures are due to the combination of the
      dynamic nature and the mechanism of the injury itself. Complications are usually
      secondary to three integral parts of this complex fracture pattern: 1) fracture
      and depression of the subtalar joint, 2) loss of the height of the calcaneal body
      with varus rotation, and 3) expansion of the lateral wall of the calcaneus. Other
      complications occur with less frequency. This article describes the complications
      and sequelae of old, malunited intra-articular calcaneal fractures in relation to
      the nature and the components of these unique fractures.

PMID- 15265999
TI  - Vancomycin: an overview for the podiatric physician.
AB  - An increased reliance on vancomycin to treat bacterial infections has led to the
      emergence of vancomycin-resistant organisms. The podiatric physician must select
      and use vancomycin with due caution. This article presents a general review of
      vancomycin's pharmacology, pharmacokinetics, and dosing recommendations.
      Literature citations of clinically based evidence regarding the development and
      use of vancomycin nomograms are also presented. A vancomycin dosing nomogram is
      introduced as an effective tool for the prescribing podiatric physician.
      Appropriate use of the information presented may improve patient outcomes and
      enable the podiatric physician to treat patients with less effort and at a lower
      cost.

PMID- 15266000
TI  - Manipulation of the ankle as a method of treatment for ankle and foot pain.
AB  - This article presents a series of case reports to describe the technique of ankle
      joint manipulation and its effects on common problems of the foot and ankle. The
      relationship between motion and pain is described, as are the effects of muscular
      inhibition on the presence of joint restriction and their association with pain
      in various joints remote to the ankle joint.

PMID- 15266001
TI  - Fibromyalgia and Tinel's sign in the foot.
AB  - In the physical examination of the patient suspected of having tarsal tunnel
      syndrome, the podiatric physician relies on Tinel's sign: tapping the posterior
      tibial nerve in the tarsal tunnel should produce a distally radiating sensation
      if the nerve is pathologically compressed at this location. The American College
      of Rheumatology recognizes fibromyalgia as a condition characterized by multiple
      "tender points" on physical examination. This report compares the locations of
      the 18 critical diagnostic fibromyalgia points with known sites of anatomical
      entrapment of peripheral nerves in the lower extremity. We also describe a
      patient with both fibromyalgia and tarsal tunnel syndrome. Tinel's sign in the
      lower extremity is a valid technique for assessing peripheral nerve compression
      in the patient with fibromyalgia.

PMID- 15266002
TI  - Modified Z-osteotomy of the hallux.
AB  - This article describes a proximal phalangeal osteotomy for the correction of
      abductus deformity of the hallux. The modification uses a Z-osteotomy, which
      retains the length of the hallux, corrects the abductus component, and provides
      excellent rigid internal fixation. This procedure may be used only in mild-to
      moderate cases.

PMID- 15266003
TI  - Calcaneal osteochondroma.

PMID- 15266004
TI  - Triple arthrodesis using external ring fixation and arched-wire compression.

PMID- 15266006
TI  - Quantitative analysis of liver protein expression during hibernation in the
      golden-mantled ground squirrel.
AB  - Mammals that enter deep hibernation experience extreme reductions in body
      temperature and in metabolic, respiratory, and heart rates for several weeks at a
      time. Survival of these extremes likely entails a highly regulated network of
      tissue- and time-specific gene expression patterns that remain largely unknown.
      To date, studies to identify differentially-expressed genes have employed a
      candidate gene approach or in a few cases broader unbiased screens at the RNA
      level. Here we use a proteomic approach to compare and identify differentially
      expressed liver proteins from two seasonal stages in the golden-mantled ground
      squirrel (summer and entrance into torpor) using two-dimensional gels followed by
      MS/MS. Eighty-four two-dimensional gel spots were found that quantitatively alter
      with the hibernation season, 68 of which gave unambiguous identifications based
      on similarity to sequences in the available mammalian database. Based on what is
      known of these proteins from prior research, they are involved in a variety of
      cellular processes including protein turnover, detoxification, purine
      biosynthesis, gluconeogenesis, lipid metabolism and mobility, ketone body
      formation, cell structure, and redox balance. A number of the enzymes found to
      change seasonally are known to be either rate-limiting or first enzymes in a
      metabolic pathway, indicating key roles in metabolic control. Functional roles
      are proposed to explain the changes seen in protein levels and their potential
      influence on the phenotype of hibernation.

PMID- 15266007
TI  - Mathematical algorithm for discovering states of expression from direct genetic
      comparison by microarrays.
AB  - Highly specific direct genome-scale expression discovery from two biological
      samples facilitates functional discovery of molecular systems. Here, expression
      data from cDNA arrays are ranked and curve-fitted. The algorithm uses filters
      based on the derivatives (slopes) of the curve fits. The rules are set to (i)
      filter the largest number of artifactual ratios from same-to-same datasets and
      (ii) maximize discovery from direct comparisons of different samples. The
      unsupervised discovery is optimized without lowering specificity. The false
      discovery rates are significantly lower than other methods. The discovered states
      of genetic expression facilitate functional discovery and are validated by real
      time RT-PCR. Better quality improves sensitivity.

PMID- 15266008
TI  - Discovery of sequence motifs related to coexpression of genes using evolutionary
      computation.
AB  - Transcription factors are key regulatory elements that control gene expression.
      Recognition of transcription factor binding site (TFBS) motifs in the upstream
      region of coexpressed genes is therefore critical towards a true understanding of
      the regulations of gene expression. The task of discovering eukaryotic TFBSs
      remains a challenging problem. Here, we demonstrate that evolutionary computation
      can be used to search for TFBSs in upstream regions of genes known to be
      coexpressed. Evolutionary computation was used to search for TFBSs of genes
      regulated by octamer-binding factor and nuclear factor kappa B. The discovered
      binding sites included experimentally determined known binding motifs as well as
      lists of putative, previously unknown TFBSs. We believe that this method to
      search nucleotide sequence information efficiently for similar motifs will be
      useful for discovering TFBSs that affect gene regulation.

PMID- 15266009
TI  - Ca2+ regulation of inositol 1,4,5-trisphosphate receptors: can Ca2+ function
      without calmodulin?
AB  - All Ca(2+) channels are regulated by Ca(2+), a feature that allows them to
      respond to their own activity and to the activities of neighboring Ca(2+)
      channels. Inhibition by Ca(2+) protects cells from potentially hazardous
      increases in cytosolic [Ca(2+)], and stimulation can mediate facilitation and
      regenerative propagation of Ca(2+) signals. Calmodulin is emerging as a key
      player in regulation of Ca(2+) channels by Ca(2+), but its role is more complex
      and more beautiful than might have been imagined.

PMID- 15266010
TI  - Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice.
AB  - Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in
      regulating neurogenesis in the adult brain. To investigate this possibility, we
      measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU),
      which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R
      KO mice showed reductions in the number of BrdU-labeled cells to approximately
      50% of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ),
      suggesting that CB1R activation promotes neurogenesis. To test this further, WT
      mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A)
      before measuring neurogenesis with BrdU. SR141716A paradoxically increased the
      number of BrdU-labeled cells by approximately 50% in SVZ; another CB1R
      antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H
      pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this
      discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated
      neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such
      non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by
      administering SR141716A to VR1-KO mice, in which the ability of SR141716A to
      enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have
      roles in regulating adult neurogenesis.

PMID- 15266011
TI  - Ligand-binding residues integrate affinity and efficacy in the NMDA receptor.
AB  - The interaction of an agonist with its receptor can be characterized by two
      fundamental properties, affinity and efficacy. Affinity defines how tightly the
      agonist associates with its receptor, and efficacy measures the ability of the
      bound ligand to activate the receptor. Although affinity and efficacy are
      independent properties, the binding and activation processes that they describe
      are tightly coupled. This strong coupling has complicated the interpretation of
      concentration-response phenotypes caused by receptor mutations. We present an
      approach that quantifies the role of individual amino acids in defining affinity
      and efficacy. This method, which employs partial agonists and covalent
      modification of introduced cysteines, was applied to the ligand-binding sites of
      the NMDA receptor. Recent crystallographic structures for glutamate receptor
      ligand-binding cores allowed identification of residues that are either known or
      are predicted to be critical for ligand binding in the NR1 and NR2A subunit,
      respectively. Mutation of amino acids whose sidechains would directly coordinate
      bound ligands affected both agonist affinity and efficacy. In contrast, positions
      predicted to stabilize the closed-cleft conformation contributed only to agonist
      efficacy. The results provide a molecular basis for the tight coupling of agonist
      binding and receptor activation.

PMID- 15266012
TI  - Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice
      and by the 5-lipoxygenase inhibitor zileuton.
AB  - The role of 5-lipoxygenase (5-LOX) in the pathophysiology of renal
      ischemia/reperfusion (I/R) injury is not known. Here we investigate the effects
      of 1) the 5-LOX inhibitor zileuton and 2) 5-LOX gene knockout (5-LOX(-/-)) mice
      on renal dysfunction and injury caused by I/R of the kidney in mice. Wild-type
      mice treated with zileuton (3 mg/kg i.v.) or 5-LOX(-/-) mice were subjected to
      bilateral renal artery occlusion (30 min) followed by reperfusion (24 h). Plasma
      urea, creatinine, and aspartate aminotransferase (AST) were measured as markers
      of renal dysfunction and reperfusion injury. Kidneys were used for histological
      evaluation of renal injury. Renal myeloperoxidase activity was measured and used
      as an indicator of polymorphonuclear leukocyte (PMN) infiltration and renal
      expression of intercellular adhesion molecule-1 (ICAM-1) was determined using
      immunohistochemistry. Administration of zileuton before I/R significantly reduced
      the degree of renal dysfunction (urea, creatinine) and injury (AST, histology).
      In addition, zileuton reduced the expression of ICAM-1 and the associated PMN
      infiltration caused by I/R of the mouse kidney. Compared with wild-type mice, the
      degree of renal dysfunction, injury, and inflammation caused by I/R in 5-LOX(-/-)
      mice was also significantly reduced, confirming the pathophysiological role of 5
      LOX in the development of renal I/R injury. We propose that 1) endogenous 5-LOX
      metabolites enhance the degree of renal injury, dysfunction, and inflammation
      caused by I/R of the kidney by promoting the expression of adhesion molecules,
      and 2) inhibitors of 5-LOX may be useful in the treatment of conditions
      associated with I/R of the kidney.

PMID- 15266013
TI  - High-affinity interactions between human alpha1A-adrenoceptor C-terminal splice
      variants produce homo- and heterodimers but do not generate the alpha1L
      adrenoceptor.
AB  - Using combinations of bioluminescence resonance energy transfer, time-resolved
      fluorescence resonance energy transfer and the functional complementation of
      pairs of inactive receptor-G protein fusion proteins, the human alpha(1A-1)
      adrenoceptor was shown to form homodimeric/oligomeric complexes when expressed in
      human embryonic kidney (HEK) 293 cells. Saturation bioluminescence resonance
      energy transfer studies indicated the alpha(1A-1)-adrenoceptor homodimer
      interactions to be high affinity and some 75 times greater than interactions
      between the alpha(1A-1)-adrenoceptor and the delta opioid peptide receptor. Only
      a fraction of the alpha(1A-1)-adrenoceptors was at the plasma membrane of HEK293
      cells at steady state. However, dimers of alpha(1A-1)-adrenoceptors were also
      present in intracellular membranes, and the dimer status of those delivered to
      the cell surface was unaffected by the presence of agonist. Splice variation can
      generate at least three forms of the human alpha(1A-1)-adrenoceptor with
      differences limited to the C-terminal tail. Each of the alpha(1A-1), alpha(1A
      2a), and alpha(1A-3a)-adrenoceptor splice variants formed homodimers/oligomers,
      and all combinations of these splice variants were able to generate
      heterodimeric/oligomeric interactions. Despite the coexpression of these splice
      variants in human tissues that possess the pharmacologically defined alpha(1L)
      adrenoceptor binding site, coexpression of any pair in HEK293 cells failed to
      generate ligand binding characteristic of the alpha(1L)-adrenoceptor.

PMID- 15266014
TI  - Structural determinants of HERG channel block by clofilium and ibutilide.
AB  - Block of human ether-a-go-go related gene (HERG) K(+) channels by a variety of
      medications has been linked to acquired long QT syndrome, a disorder of cardiac
      repolarization that predisposes to lethal arrhythmias. The drug-binding site is
      composed of residues that face into the central cavity of the channel. Two
      aromatic residues located on the S6 domain (Tyr652 and Phe656) are particularly
      important structural determinants of drug block. The role of pore helix residues
      (Thr623, Ser624, Val625) is less clear. In this study, we compared the
      pharmacological properties of two structurally related compounds, ibutilide and
      clofilium. Both compounds are charged amines with a single phenyl ring.
      Clofilium, a chlorobenzene derivative, is a potent blocker of HERG channels, but
      has a remarkably slower time course for recovery from block than ibutilide, a
      methanesulfonanilide. The difference in the rate of recovery from block can be
      explained simply by variation in drug trapping. There is little recovery from
      clofilium block with D540K HERG channels that permit untrapping at hyperpolarized
      potentials. Alanine-scanning mutagenesis of the S6 domain and a portion of the
      pore helix revealed that the binding site residues were the same for both
      compounds. However, S624A, located at the base of the pore helix, was the only
      HERG mutation that enabled rapid recovery from clofilium block. In summary, the
      pore helix residues are important components of the HERG drug binding site, and
      may be particularly important for drugs with polar substituents, such as a
      halogen (e.g., clofilium) or a methanesulfonamide (e.g., ibutilide).

PMID- 15266015
TI  - Identification of a novel site within G protein alpha subunits important for
      specificity of receptor-G protein interaction.
AB  - Several domains of G protein alpha subunits are implicated in the control of
      receptor-G protein coupling specificity. Among these are the extreme N-and C
      termini, the alpha4/beta6-loops, and the loop linking the N-terminal alpha-helix
      to the beta1-strand of the ras-like domain. In this study, we illustrate that
      single-point mutations of a highly conserved glycine residue within the linker I
      region of the Galpha(q) subunit confers upon the mutant Galpha(q) the ability to
      be activated by Galpha(i)- and Galpha(s) -coupled receptors, as evidenced by
      guanosine 5'-O-(3-[(35)S]thio)triphosphate binding and inositol phosphate
      turnover assays. The mutations did not affect expression of Galpha(q) proteins
      nor their ability to stimulate phospholipase Cbeta. It is noteworthy that both
      mutant and wild-type Galpha(q) proteins are indistinguishable in their ability to
      reconstitute a functional Gq-PLCbeta-calcium signaling pathway when cotransfected
      with the Galpha(q)-coupled neurokinin 1 or muscarinic M3 receptor into mouse
      embryonic fibroblasts derived from Galpha(q/11) knockout mice. On a three
      dimensional model of the receptor-G protein complex, the highly conserved linker
      I region connecting the helical and the GTPase domain of the Galpha protein is
      inaccessible to the intracellular surface of the receptors. Our data indicate
      that receptor-G protein coupling specificity is not exclusively governed by
      direct receptor-G protein interaction and that it even bypasses the requirement
      of the extreme C terminus of Galpha, a well accepted receptor recognition domain,
      suggesting a novel allosteric mechanism for G protein-coupled receptor-G protein
      selectivity.

PMID- 15266016
TI  - Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic
      receptor single- and double-knockout mice.
AB  - Identification of the specific muscarinic acetylcholine receptor (mAChR) subtypes
      mediating stimulation of salivary secretion is of considerable clinical interest.
      Recent pharmacological and molecular genetic studies have yielded somewhat
      confusing and partially contradictory results regarding the involvement of
      individual mAChRs in this activity. In the present study, we re-examined the
      roles of M(1) and M(3) mAChRs in muscarinic agonist-mediated stimulation of
      salivary secretion by using M(1) and M(3) receptor single-knockout (KO) mice and
      newly generated M(1)/M(3) receptor double-KO mice. When applied at a low dose (1
      mg/kg, s.c.), the muscarinic agonist pilocarpine showed significantly reduced
      secretory activity in both M(1) and M(3) receptor single-KO mice. However, when
      applied at higher doses, pilocarpine induced only modestly reduced (5 mg/kg,
      s.c.) or unchanged (15 mg/kg, s.c.) salivation responses, respectively, in M(1)
      and M(3) receptor single-KO mice, indicating that the presence of either M(1) or
      M(3) receptors is sufficient to mediate robust salivary output. Quantitative
      reverse transcriptase-polymerase chain reaction studies with salivary gland
      tissue showed that the inactivation of the M(1) or M(3) mAChR genes did not lead
      to significantly altered mRNA levels of the remaining mAChR subtypes. Strikingly,
      the sialagogue activity of pilocarpine was abolished in M(1)/M(3) receptor double
      KO mice. However, salivary glands from M(1)/M(3) receptor double-KO mice remained
      responsive to stimulation by the beta-adrenergic receptor agonist, (S)
      isoproterenol. Taken together these studies support the concept that a mixture of
      M(1) and M(3) receptors mediates cholinergic stimulation of salivary flow.

PMID- 15266017
TI  - Strategies for inhibition of MDR1 gene expression.
AB  - Several distinct strategies have been used to modulate the expression of cancer
      associated genes, including antisense oligonucleotides, small interfering RNAs
      (siRNAs), and artificial transcriptional factors. One major cause for
      chemotherapeutic treatment failure in cancer is the overexpression of P
      glycoprotein, the product of the multidrug resistance gene MDR1. In this study,
      we tested the ability of siRNAs to inhibit MDR1 gene expression. We evaluated the
      efficiency of chemically synthesized dsRNAs as well as vector-based hairpin
      siRNAs and investigated the behavior of clones of multidrug-resistant NCI/ADR-RES
      breast carcinoma cells stably transfected with hairpin siRNA vectors. The effects
      of siRNA on the MDR phenotype were compared with those elicited by antisense
      oligonucleotides or by designed transcription factors targeting the MDR1
      promoter. These studies suggest that there are several comparably effective
      strategies for inhibiting MDR1 expression.

PMID- 15266018
TI  - The N-terminal Ca2+-independent calmodulin-binding site on the inositol 1,4,5
      trisphosphate receptor is responsible for calmodulin inhibition, even though this
      inhibition requires Ca2+.
AB  - Calmodulin (CaM) is a ubiquitous Ca(2+)-sensor protein that plays an important
      role in regulating a large number of Ca(2+) channels, including the inositol
      1,4,5-trisphosphate receptor (IP(3)R). CaM binds to the IP(3)R at Ca(2+)
      dependent as well as at Ca(2+)-independent interaction sites. In this study, we
      have investigated the Ca(2+)-independent CaM-binding site for its role in the
      regulation of the Ca(2+)-dependent bell-shaped activation curve of the IP(3)R.
      Suramin, a polysulfonated napthylurea, displaced CaM in both the presence and the
      absence of Ca(2+). Suramin competed with CaM for binding to different peptides
      representing the previously identified CaM-binding sites on IP(3)R1. By
      interacting with the N-terminal Ca(2+)-independent CaM-binding site, suramin
      mimicked the functional effect of CaM and induced an allosteric but competitive
      inhibition of IP(3) binding. Therefore, suramin also potently inhibited IP(3)
      induced Ca(2+) release (IICR) from permeabilized cells predominantly expressing
      IP(3)R1 (L15 fibroblasts) or IP(3)R3 (Lvec fibroblasts), even though the IP(3)R3
      does not contain Ca(2+)-dependent CaM-binding sites. Furthermore, we have found
      that CaM(1234), a CaM mutated in its four EF hands, inhibited IICR in a Ca(2+)
      dependent way with the same potency as CaM. We conclude that CaM inhibits IICR
      via the N-terminal binding site. The inhibition requires Ca(2+) but CaM itself is
      not the Ca(2+) sensor for the inhibition of the IP(3)R.

PMID- 15266019
TI  - Synergistic antitumor activity of troxacitabine and camptothecin in selected
      human cancer cell lines.
AB  - Troxacitabine (L-OddC) is an L-configuration deoxycytidine analog currently in
      phase II trials for the treatment of cancer. The cytotoxicity of L-OddC in
      combination with other anticancer agents has not been studied systematically. In
      the present study, we assessed the cytotoxic effects produced by the combinations
      of L-OddC and several commonly used chemotherapy drugs in a panel of cultured
      human cancer cell lines. Growth inhibition resulting from simultaneous exposure
      to two-drug combinations was determined using the methylene blue staining method.
      Camptothecin (CPT) and analogs exhibited additives to synergistic interactions
      with L-OddC by isobologram analysis. These effects were cell type-specific, with
      the most pronounced synergism being observed in KB oropharyngeal carcinoma and
      CPT-resistant KB100 cell lines. In KB cells, the total cellular uptake and DNA
      incorporation of L-OddC were increased by the addition of CPT. One explanation
      that emerged from enzyme assays of deoxycytidine kinase (dCK) and deoxycytidine
      monophosphate kinase (dCMPK), key enzymes involved in L-OddC phosphorylation, was
      that CPT protected against L-OddC-induced reduction in dCK and dCMPK activity.
      The resulting increase in l-OddC metabolites and incorporation into DNA was
      associated with enhanced L-OddC cytotoxicity. These findings will be useful in
      designing future clinical trials of combination chemotherapy with l-OddC and CPT
      analogs with the potential for a broad use against both hematological and solid
      tumors.

PMID- 15266020
TI  - Prostaglandin E2 inhibits the phospholipase D pathway stimulated by formyl
      methionyl-leucyl-phenylalanine in human neutrophils. Involvement of EP2 receptors
      and phosphatidylinositol 3-kinase gamma.
AB  - Prostaglandin E(2) (PGE(2)), originally discovered as a pro-inflammatory
      mediator, also inhibits several chemoattractant-elicited neutrophil functions,
      including adhesion, secretion of cytotoxic enzymes, production of superoxide
      anions, and chemotaxis. In this study, we have examined the effects of PGE(2) and
      prostaglandin E (EP) receptor-selective agonists/antagonists on several steps of
      the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD)
      activation pathway in human neutrophils to elucidate the PGE(2) inhibitory
      mechanism. PGE(2) and EP(2) receptor agonists inhibited the stimulation of the
      activity of PLD induced by fMLP in a concentration-dependent manner. The fMLP
      stimulated translocation to membranes of protein kinase C alpha, Rho, and Arf
      GTPases was diminished in the presence of PGE(2) or EP(2) agonists. Moreover,
      PGE(2) and EP(2) agonists decreased the activation of phosphatidylinositol 3
      kinase gamma (PI3Kgamma) and Tec kinases as well as the tyrosine phosphorylation
      of proteins stimulated by fMLP. These data provide strong evidence that 1) the
      inhibitory effects of PGE(2) on the fMLP-induced PLD activation pathway were
      mediated via EP(2) receptors and that 2) the suppression of PI3Kgamma activity
      was the crucial step in the EP(2)-mediated inhibition of the fMLP-induced
      signaling cascade.

PMID- 15266021
TI  - p38 Mitogen-activated protein kinase mediates synergistic induction of inducible
      nitric-oxide synthase by lipopolysaccharide and interferon-gamma through signal
      transducer and activator of transcription 1 Ser727 phosphorylation in murine
      aortic endothelial cells.
AB  - Nitric oxide (NO) can be produced in large amounts by up-regulation of inducible
      NO synthase (iNOS). iNOS is induced in many cell types by pro-inflammatory
      agents, such as bacterial lipopolysaccharide (LPS) and cytokines. Overproduction
      by endothelial cells (EC) may contribute to vascular diseases. In contrast to
      macrophages, murine aortic endothelial cells (MAEC) produced no NO in response to
      either LPS or interferon gamma (IFNgamma), whereas combined treatment was highly
      synergistic. In this study, we investigated the mechanisms of synergy in MAEC.
      LPS activated p38 mitogen-activated protein kinase (MAPK), whereas IFNgamma
      activated Janus kinase and signal transducer and activator of transcription-1
      (STAT1). Both pathways were required for iNOS induction because herbimycin A, a
      tyrosine kinase inhibitor, and 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4
      pyridyl)1H-imidazole. HCl (SB202190), a p38 MAPKalpha/beta inhibitor, each
      blocked induction. LPS increased the phosphorylation of STAT1alpha at serine 727
      in IFNgamma-treated MAEC. SB202190, but not 2'-amino-3'-methoxyflavone (PD98059),
      an inhibitor of p44/p42 MAPK activation, abolished the phosphorylation and
      induction of iNOS. SB202190 did not affect tyrosine 701 phosphorylation or
      nuclear translocation of STAT1. However, STAT1-DNA binding activity was reduced
      by SB202190. Although LPS stimulated the DNA binding activity of nuclear factor
      kappaB and activating protein-1, combined treatment with IFNgamma did not enhance
      activation, and SB202190 did not inhibit it. The results indicate that p38
      MAPKalpha and/or beta are required for the synergistic induction of iNOS by LPS
      and IFNgamma in MAEC. Furthermore, the synergistic induction is associated with
      phosphorylation of STAT1alpha serine 727 in MAEC. This observation may explain
      potentially beneficial effects of p38 MAPK inhibitors in vascular inflammatory
      diseases.

PMID- 15266022
TI  - Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct
      ligand interaction properties compared with MT2 homodimers.
AB  - Heterodimerization has been documented for several members of the G protein
      coupled receptor (GPCR) superfamily, including the closely related MT(1) and
      MT(2) melatonin receptors. However, the relative abundance of hetero-versus
      homodimers and the specific properties, which can be attributed to each form, are
      difficult to determine. Using a bioluminescence resonance energy transfer (BRET)
      donor saturation assay, we show that half-maximal MT(1)/MT(2) heterodimer
      formation is reached for expression levels as low as approximately 4000 receptors
      per cell. The relative propensity of MT(1) homodimer and MT(1)/MT(2) heterodimer
      formation are similar, whereas that for the MT(2) homodimer formation is 3- to 4
      fold lower. These data indicate that both the relative expression level of each
      receptor isoform and the affinities between monomers may determine the actual
      proportion of homo- and heterodimers. The specific interaction of ligands with
      the MT(1)/MT(2) heterodimer was studied using a BRET-based assay as a readout for
      the conformational changes of the heterodimer. An MT(1)/MT(2) heterodimer
      specific profile and ligands selective for the MT(1)/MT(2) heterodimer compared
      with the MT(2) homodimer could be identified. Classic radioligand binding and
      BRET studies suggest that heterodimers contain two functional ligand binding
      sites that maintain their respective selectivity for MT(1) and MT(2) ligands.
      Occupation of either binding site is sufficient to induce a conformational change
      within the heterodimer. Taken together, these results show that the probability
      of GPCR heterodimer formation may be equal to or even higher than that of the
      corresponding homodimers and that specific properties of heterodimers can be
      revealed using a BRET-based ligand/receptor interaction assay.

PMID- 15266023
TI  - Tumor necrosis factor-alpha differentially regulates the expression of
      proinflammatory genes in human airway smooth muscle cells by activation of
      interferon-beta-dependent CD38 pathway.
AB  - Recent evidence suggests that CD38, an ectoenzyme that converts NAD(+) to cyclic
      ADP-ribose (cADPr), may play a role in cytokine-induced airway smooth muscle
      (ASM) cell hyper-responsiveness, a key feature associated with chronic asthma. In
      the present study, we investigated the major signaling pathways by which tumor
      necrosis factor-alpha (TNFalpha) induces CD38 expression and its role in
      regulating gene expression in human ASM cells. Using flow cytometry analyses,
      TNFalpha enhanced CD38 expression in a manner that was time-(0-24 h),
      concentration-(0.1-40 ng/ml), and protein synthesis-(cycloheximide blockade)
      dependent. A selective agonistic antibody against tumor necrosis factor receptor
      (TNFR) 1 also augmented CD38 expression, whereas anti-TNFR2 antagonistic antibody
      did not prevent the TNFalpha response. Inhibition of the Janus activated
      kinase/signal transducer and activator of transcription pathways using the
      soluble inhibitor 2-(1,1-dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz
      [h]imidaz[4,5-f]isoquinolin-7-one (DBI) or with neutralizing antibody against
      interferon beta (IFNbeta) completely abrogated TNFalpha-induced CD38 expression
      at both protein and mRNA levels. Combining TNFalpha (0.1 and 1 ng/ml) and IFNbeta
      (100 IU/ml) at concentrations alone that had little effect on CD38 expression
      induced a robust synergistic induction of CD38 mRNA and protein levels. 8-Bromo
      cADPr, a cADPr antagonist, significantly augmented TNFalpha-induced interleukin-6
      secretion, whereas regulated on activation normal T cell expressed and secreted
      secretion was suppressed. 8-Bromo-cADPr, however, did not affect TNFalpha-induced
      cell surface expression of intercellular adhesion molecule-1. Our study is the
      first to demonstrate that IFNbeta-dependent activation of CD38 pathway is a novel
      component by which TNFalpha differentially regulates the expression of
      inflammatory genes in ASM cells.

PMID- 15266024
TI  - Unexpected mexiletine responses of a mutant cardiac Na+ channel implicate the
      selectivity filter as a structural determinant of antiarrhythmic drug access.
AB  - Gating properties of Na(+) channels are the critical determinants for the state
      dependent block by class I antiarrhythmic drugs; however, recent site-directed
      mutagenesis studies have shown that the Na(+) channel selectivity filter region
      controls drug access to and dissociation from the binding site. To validate these
      observations, we have exploited a naturally occurring cardiac Na(+) channel
      mutation, S1710L, located next to the putative selectivity filter residue of
      domain 4, and evaluated the pharmacological properties to mexiletine using whole
      cell, patch-clamp recordings. Consistent with the large negative shift of steady
      state inactivation and the enhanced slow inactivation, the S1710L channel showed
      greater mexiletine tonic block than wild-type (WT) channel. In contradiction,
      S1710L showed attenuated use-dependent block by mexiletine and accelerated
      recovery from block, suggesting that the drug escape though the external access
      path is facilitated. Extracellularly applied QX-314, a membrane-impermeant
      derivative of lidocaine, elicited significantly enhanced tonic block in S1710L
      similar to mexiletine. However, recovery from internally applied QX-314 was
      accelerated by 4.4-fold in S1710L compared with WT. These results suggest that
      the drug access to and dissociation from the binding site through the hydrophilic
      path are substantially altered. Moreover, K(+) permeability was 1.9-fold
      increased in S1710L, verifying that the mutated residue is located in the ion
      conducting pore. We propose that the Na(+) channel selectivity filter region is a
      structural determinant for the antiarrhythmic drug sensitivity in addition to
      gating properties of the indigenous Na(+) channels that govern the state
      dependent drug block.

PMID- 15266025
TI  - Interleukin-1beta-induced mucin production in human airway epithelium is mediated
      by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A
      signaling.
AB  - We reported recently that interleukin (IL)-1beta exposure resulted in a prolonged
      increase in MUC5AC mucin production in normal, well differentiated, human
      tracheobronchial epithelial (NHTBE) cell cultures, without significantly
      increasing MUC5AC mRNA (Am J Physiol 286:L320-L330, 2004). The goal of the
      present study was to elucidate the signaling pathways involved in IL-1beta
      induced MUC5AC production. We found that IL-1beta increased cyclooxygenase-2 (COX
      2) mRNA expression and prostaglandin (PG) E(2) production and that the COX-2
      inhibitor celecoxib suppressed IL-1beta-induced MUC5AC production. Addition of
      exogenous PGE(2) to NHTBE cultures also increased MUC5AC production and IL-1beta
      induced Muc5ac hypersecretion in tracheas from wild-type but not from COX-2-/-
      mice. NHTBE cells expressed all four E-prostanoid (EP) receptor subtypes and
      misoprostol, an EP2 and EP4 agonist, increased MUC5AC production, whereas
      sulprostone, an EP1 and EP3 agonist, did not. Furthermore, specific protein
      kinase A (PKA) inhibitors blocked IL-1beta and PGE(2)-induced MUC5AC production.
      However, neither inhibition of epidermal growth factor receptor (EGFR) activation
      with the tyrosine kinase inhibitor 4-(3-chloroanilino)-6,7-dimethoxyquinazoline
      HCl (AG-1478) or EGFR blocking antibody nor inhibition of extracellular signal
      regulated kinase/P-38 mitogen activated protein kinases with specific inhibitors
      blocked IL-1beta stimulation of MUC5AC mucin production. We also observed that
      tumor necrosis factor (TNF)-alpha, platelet activating factor (PAF), and
      lipopolysaccharide (LPS) induced COX-2 and increased MUC5AC production that was
      blocked by celecoxib, suggesting a common signaling pathway of inflammatory
      mediator-induced MUC5AC production in NHTBE cells. We conclude that the induction
      of MUC5AC by IL-1beta, TNF-alpha, PAF, and LPS involves COX-2- generated PGE(2),
      activation of EP2 and/or EP4 receptor(s), and cAMP-PKA-mediated signaling.

PMID- 15266026
TI  - Differential modulation of beta2 and beta4 subunits of human neuronal nicotinic
      acetylcholine receptors by acidification.
AB  - We have shown previously that acidification increases the affinity of agonists to
      rat alpha3beta4 nicotinic acetylcholine receptors (nAChR) and accelerates both
      the activation and decay kinetics of agonist-induced currents recorded from human
      embryonic kidney 293 cells stably expressing the receptor (Abdrakhmanova et al.,
      2002b). Here, we report on experiments examining the effect of rapid
      acidification on four different subtypes (alpha3beta4alpha5, alpha4beta2,
      alpha3beta2, and alpha3beta2alpha5) of human neuronal nAChRs stably expressed in
      tsA201 cells using a piezoelectric device for rapid (<5 ms) solution application.
      Application of ACh, at its EC(50) concentration for each nAChR subtype, at pH
      values 7.4 and 6.0, showed that acidification, similarly to that reported for rat
      alpha3beta4 acetylcholine receptors (AChRs), increased the amplitude and
      accelerated the activation and decay kinetics of the currents in human
      alpha3beta4alpha5 AChRs by increasing their affinity to the agonist. In sharp
      contrast, acidification reduced the amplitude but accelerated the decay kinetics
      of the current in all human beta2-containing nAChR subtypes (alpha3beta2,
      alpha3alpha5beta2, alpha4beta2) examined in this study. Brief application of ACh
      at saturating concentration (1 mM) on alpha3beta4alpha5 AChRs induced a "rebound
      current" upon rapid washout of the agonist at pH 7.4, but no "rebound current"
      was observed in alpha3beta2 AChRs. Surprisingly, acidification, pH 6.0, applied
      only during the agonist pulse also accelerated the decay kinetics of the "rebound
      current". Our data provide evidence for the specificity of proton-induced
      modulation of neuronal nAChRs based on their beta subunit composition.
      Furthermore, in alpha3beta4alpha5 AChR, we find that protonation effects may
      persist, after washout of acidic solutions, consistent with proton-induced
      conformational changes of the receptor.

PMID- 15266027
TI  - "Induced-fit" mechanism for catecholamine binding to the beta2-adrenergic
      receptor.
AB  - We engineered single and multiple mutations of serines 203, 204, and 207 in the
      fifth transmembrane domain of the beta(2)-adrenergic receptor, a region known to
      interact with hydroxyl groups of the catechol ring. Using such mutants, we
      measured the binding affinities of a panel of six catecholamine agonists
      differing only in the presence of substituents in the ethanolamine tail of the
      molecule. Although all ligands shared an intact catechol ring, they exhibited
      different losses of binding energy in response to the mutations. For all
      mutations, we found a clear relationship between the loss of binding caused by
      receptor mutation and that caused by the ligand modification. This indicates that
      the catechol ring and the ethanolamine tail synergistically influence their
      respective interactions when binding to the receptor. To verify this idea by a
      formal thermodynamic test, we used a double-mutant cycle analysis. We compared
      the effects of each receptor mutation with those induced by the modifications of
      the ligand's tail. Because such changes disrupt interactions occurring at
      different receptor domains, they should produce cumulative losses. In contrast,
      we found positive cooperativity between such effects. This means that the binding
      of each side of the catecholamine can enhance the binding of the other, through
      an effect that is probably propagated via a conformational change. We suggest
      that the agonist-binding pocket is not rigid but is dynamically formed as the
      ligand builds an increasing number of contacts with the receptor.

PMID- 15266028
TI  - Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function.
AB  - BACKGROUND: Tamm-Horsfall protein (THP), a glycoprotein produced exclusively by
      renal tubular cells, is thought to be involved in several inflammatory disorders
      such as bacterial interstitial nephritis as well as in defence against
      uropathogenic microorganisms. The specific effects of THP on inflammatory cells,
      however, are not yet well known. Therefore, the present study investigates the
      effects of THP in its soluble form on distinct polymorphonuclear leukocyte (PMNL)
      functions. METHODS: PMNL were isolated from the venous blood of healthy adult
      donors and incubated at low THP concentrations (70-350 ng/ml), resembling plasma
      concentrations, and at high THP concentrations (1.75-8.75 micro g/ml), resembling
      urinary concentrations. RESULTS: High (urinary) THP concentrations inhibited PMNL
      apoptosis and chemotaxis and stimulated PMNL phagocytosis, while low (plasma) THP
      concentrations increased PMNL chemotaxis. CONCLUSIONS: These data indicate that
      THP influences several PMNL functions, suggesting a crucial immunomodulatory role
      for this glycoprotein in host defence mechanisms of the kidney and genitourinary
      tract.

PMID- 15266029
TI  - Haemodynamics and electrolyte balance: a comparison between on-line pre-dilution
      haemofiltration and haemodialysis.
AB  - BACKGROUND: An important advantage of convective therapies is improved vascular
      reactivity. However, it is not well known whether the vascular response during
      convective therapies remains superior when compared to haemodialysis (HD) with an
      adjusted temperature of the dialysate. It has also been suggested that convective
      therapies may impair small electrolyte removal through an effect on the Donnan
      equilibrium. In the present study, we compared the haemodynamic response and
      small electrolyte removal between pre-dilution on-line haemofiltration (HF) and
      HD procedures. METHODS: Cardiac output (CO), central blood volume (CBV) and
      peripheral vascular resistance (PVR) were assessed, using the saline dilution
      technique, in 12 stable patients during HF and HD with two different temperatures
      of the dialysate [36.5 and 35.5 degrees C (HD(36.5) and HD(35.5))]. Balances for
      sodium, potassium, calcium and conductivity were assessed using total
      dialysate/filtrate collections. Target filtration volume for HF was 1.2 times
      body weight. The temperature of the infusate was 36.5 degrees C. RESULTS: The
      change (Delta) in CBV was less during HD with a dialysate temperature of 35.5
      degrees C (-0.03+/-0.14 l; P<0.05) compared to HF (-0.16+/-0.05 l) and HD(36.5) (
      0.11+/-0.14 l), but the other haemodynamic parameters did not differ between the
      studied techniques. DeltaPVR was significantly related to DeltaCBV (r = -0.46;
      P<0.01), whereas DeltaCBV was related to ultrafiltration rate (r = -0.34; P =
      0.05). DeltaCO was related to DeltaCBV (r = 0.62; P<0.001). Solute balances did
      not differ between HF and HD. CONCLUSION: Using the saline dilution method, no
      difference in the change in CO and PVR was observed between on-line HF vs
      HD(36.5) and HD(35.5). Only CBV declined to a significantly lesser degree during
      HD(35.5), although absolute differences were small. Changes in the other
      haemodynamic variables appeared more dependent upon the degree and rapidity of
      fluid removal than upon the treatment modality. No difference in small
      electrolyte balance was observed between HF and HD, suggesting that ionic removal
      is not impaired during on-line HF.

PMID- 15266030
TI  - Re-evaluation and modification of the Stuivenberg Hospital Acute Renal Failure
      (SHARF) scoring system for the prognosis of acute renal failure: an independent
      multicentre, prospective study.
AB  - BACKGROUND: A prognostic scoring system for hospital mortality in acute renal
      failure (Stuivenberg Hospital Acute Renal Failure, SHARF score) was developed in
      a single-centre study. The scoring system consists of two scores, for the time of
      diagnosis of acute renal failure (ARF) and for 48 h later, each originally based
      on four parameters (age, serum albumin, prothrombin time and heart failure). The
      scoring system was now tested and adapted in a prospective study. METHODS: The
      study involved eight intensive care units. We studied 293 consecutive patients
      with ARF in 6 months. Their mortality was 50.5%. The causes of ARF were medical
      in 184 (63%) patients and surgical in 108 (37%). In the latter group, 74 (69%)
      patients underwent cardiac and 19 (18%) vascular surgery. RESULTS: As the
      performance of the original SHARF scores was much lower in the multicentre study
      than in the original single-centre study, we re-analysed the multicentre data to
      customize the original model for the population studied. The independent
      variables were the score developed in the original study plus all additonal
      parameters that were significant on univariate analysis. The new multivariate
      analysis revealed an additional subset of three parameters for inclusion in the
      model (serum bilirubin, sepsis and hypotension). For the modified SHARF II score,
      r(2) was 0.27 at 0 and 0.33 at 48 h, respectively, the receiver operating
      characteristic (ROC) values were 0.82 and 0.83, and the Hosmer-Lemeshow goodness
      of-fit P values were 0.19 and 0.05. CONCLUSION: After customizing and by using
      two scoring moments, this prediction model for hospital mortality in ARF is
      useful in different settings for comparing groups of patients and centres,
      quality assessment and clinical trials. We do not recommend its use for
      individual patient prognosis.

PMID- 15266031
TI  - Modulation of gene expression by moxonidine in rats with chronic renal failure.
AB  - BACKGROUND: Sympathetic overactivity is a hallmark of chronic renal failure. In a
      previous experimental study, the sympatholytic drug moxonidine (MOX) had
      beneficial effects on progression of chronic renal failure. The present study
      investigates whether moxonidine influences the expression of genes associated
      with adaptive changes in kidneys of subtotally nephrectomized rats. METHODS: RNA
      was isolated from remnant kidneys of sham-operated, subtotally nephrectomized
      (SNX) and moxonidine-treated SNX (SNX-M) rats 12 weeks after operation. Genes
      that might play a role in renal adaptation processes after subtotal nephrectomy
      were selected and their expression was analysed by real-time reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: After subtotal
      nephrectomy, there was an increase in gene expression of cysteine protease
      cathepsin (H + L), ATP receptor subtypes P2Y(2) and P2Y(6), cell cycle regulator
      p21 and transforming growth factor-beta1 (TGF-beta1), and a decrease of the
      metalloprotease aminopeptidase-M (APM), membrane transporter megalin, ageing
      related klotho, type I TGF-beta receptor, mitochondrial cytochrome oxidase-1,
      kallikrein, leucine zipper-1, matrix-degrading metalloprotease meprin, the
      organic anion transporter and the P2 receptor subtypes P2Y(1) and P2Y(4). In SNX
      M rats, mRNA levels of APM, megalin, klotho, TGF-beta1, type I TGF-beta receptor,
      p21, P2Y(1) and P2Y(2) were shifted back towards control levels. CONCLUSIONS:
      Several genes showing altered expression levels after subtotal nephrectomy were
      identified in remnant kidneys. These genes might act as candidates to promote
      disease progression. The sympatholytic drug moxonidine, at a concentration devoid
      of blood pressure effects, regulates the renal expression of some of these genes
      back towards control levels. To what extent sympathetic neurotransmitters
      directly alter expression of these genes in cultured renal cells currently is
      under investigation.

PMID- 15266032
TI  - Evaluation of long-term transport ability of a bioartificial renal tubule device
      using LLC-PK1 cells.
AB  - BACKGROUND: Haemodialysis therapy does not provide renal tubule function, such as
      active fluid and solute transport, nor metabolic or endocrine action. Moreover,
      this treatment is usually associated with serious complications and high
      mortality. We constructed a bioartificial renal tubule device by using renal
      tubule epithelial cells in an artificial membrane, and evaluated transport
      properties of the device for 2 weeks. METHODS: A renal epithelial cell line, LLC
      PK(1) (Lewis-lung cancer porcine kidney), was seeded on polysulfone hollow fibres
      in small and large modules. We studied perfusion and leakage of urea nitrogen
      (UN) and creatinine (Cr), as well as reabsorption of water, glucose and sodium
      for a period of 2 weeks. RESULTS: Cell-lined hollow fibre membranes significantly
      reduced the leakage of UN and Cr throughout the 2 week period. Reabsorption of
      water, glucose and sodium were adequate from days 3 to 10 and gradually decreased
      thereafter. LLC-PK(1) cells actively transported these substances. Scanning
      electron microscopy revealed that cells in the hollow fibres on day 8 became
      completely confluent. However, they became multi-layered and almost obstructed
      the hollow fibres on day 13. CONCLUSIONS: This bioartificial renal tubule device
      functioned to reabsorb water, glucose and sodium for approximately 10 days. This
      is the first report of successful long-term evaluation of a bioartificial renal
      tubule device. This device, in combination with continuous haemofiltration, may
      provide treatment to prevent complications of dialysis and raise the quality of
      life in chronic renal failure patients.

PMID- 15266033
TI  - IGG and complement receptor expression on peripheral white blood cells in uraemic
      children.
AB  - BACKGROUND: Phagocytosis of IgG- or complement-opsonized bacteria and antibody
      production by lymphocytes are regulated by cell surface receptors for IgG
      (FcgammaRI, FcgammaRII and FcgammaRIII) and complement (CR1 and CR3). We measured
      the effect of uraemia and dialysis treatment on FcgammaR and CR expression on
      leukocytes in blood. METHODS: Blood samples were obtained from children: 40
      treated with peritoneal dialysis (PD), 23 with haemodialysis (HD), 46 not yet
      dialysed (CRF) and 33 healthy (HC). White blood cells, isolated from EDTA-blood
      by centrifugation after cell fixation with paraformaldehyde, were labelled with
      FITC-conjugated CD16 (FcgammaRIII), CD32 (FcgammaRII), CD64 (FcgammaRI), CD11b
      (CR3) and CD35 (CR1) monoclonal antibodies and analysed by flow cytometry.
      RESULTS: In PD, HD, CRF and HC, monocytes and neutrophils were all positive for
      FcgammaR and CR, except for CD16 on monocytes (20% positive). Lymphocytes
      expressed CD16 and CD32 but not CD64. PD, HD and CRF children had lower
      percentages of CD16(+) and CD32(+) lymphocytes compared with HC. The percentage
      of CD11b(+) lymphocytes was lower only in PD and the percentage of CD35(+)
      lymphocytes was lower in HD and CRF compared with HC. The median CD32 mean
      fluorescense intensity (MFI) on lymphocytes, monocytes and neutrophils was lower
      in PD, HD and CRF compared with HC. On the other hand, CD11b MFI on lymphocytes,
      monocytes and neutrophils was higher in PD, HD and CRF children compared with HC.
      CD16 and CD64 MFI were not different among the groups and CD35 MFI was only lower
      on lymphocytes from PD, HD and CRF compared with HC. CONCLUSIONS: In children
      with chronic renal failure, whether dialysed or not, FcgammaRII expression on
      lymphocytes, monocytes and neutrophils was reduced and CR3 expression was
      increased. Furthermore, CR1 expression on lymphocytes, important for the humoral
      response, was lower in children with renal failure. Age and uraemia are
      associated with these abnormalities and might contribute to impaired immune
      function in children with chronic renal failure.

PMID- 15266034
TI  - Daily on-line haemodiafiltration: a pilot trial in children.
AB  - BACKGROUND: Despite major improvements in paediatric dialysis over the last two
      decades, cardiovascular outcome is often poor. As France gives priority to kidney
      transplantation over dialysis, children in chronic haemodialysis are generally
      pre-adolescents or adolescents with long medical histories and low compliance. In
      them, the usual weekly schedule of dialysis is often unsuitable. We conducted a
      study of conversion to daily dialysis, which allowed an enhanced dialysis dose, a
      gentle ultrafiltration rate and achievement of dry body weight. METHODS: In this
      single-centre, observational, prospective, non-randomized study, five oligoanuric
      dialysis patients (mean age: 13.8 +/- 3.2 years) were converted from standard on
      line haemodiafiltration (S-OL-HDF) (4 h, three times/week) to daily on-line
      haemodiafiltration (D-OL-HDF) (3 h, six times/week). Patient selection was based
      on both the presence of uraemic cardiomyopathy (left ventricular hypertrophy and
      reduced fractional shortening) and their reduced therapeutic compliance. The D-OL
      HDF parameters were the same as for the S-OL-HDF. RESULTS: Increasing the number
      of sessions from three to six weekly positively impacted the weekly dialysis
      dose. On D-OL-HDF, mean arterial blood pressure decreased significantly (from 95
      +/- 15 to 82 +/- 13 and 87 +/- 9 mmHg at 6 and 12 months, respectively). Left
      ventricular hypertrophy decreased and its fractional shortening improved markedly
      (from 26.6 +/- 17% to 31 +/- 14% and 46.6 +/- 15% at 6 and 12 months,
      respectively). Pre-dialytic plasma phosphorus also decreased markedly (from 1.87
      +/- 0.23 to 1.43 +/- 0.22 and 1.28 +/- 0.29 mmol/l at 6 and 12 months,
      respectively), as did the calcium-phosphorus product. The post-dialytic recovery
      time disappeared and so did perception of fatigue. Fasting the day before
      dialysis to avoid excess weight gain (necessitating longer dialysis) disappeared.
      Combined with an improved appetite, these changes resulted in higher caloric and
      protein intake (nPCR), from 1.28 +/- 0.23 to 1.43 +/- 0.24 g/kg at 6 months, and
      school attendance became regular. The only pre-pubertal child included showed
      catch-up growth. CONCLUSIONS: Increasing dialysis frequency to daily sessions
      without shortening the durations of sessions excessively allowed us to overcome
      the "free diet" imposed on these paediatric, very uncompliant patients. This
      strategy led to a reduction in blood pressure and an improvement of left
      ventricular size and function, normalization of pre-dialytic plasma phosphorus
      and improvements in general well-being and dialysis acceptance. Long-term,
      however, this protocol is only acceptable for the children if associated with the
      potential of clinical recovery allowing inscription on the kidney transplantation
      waiting list.

PMID- 15266035
TI  - Critical limb ischaemia as a main cause of death in patients with end-stage renal
      disease: a single-centre study.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) have a high overall
      mortality rate, particularly due to cardiovascular morbidity. In an era of
      decline in cardiovascular diseases and early cardiovascular intervention, non
      cardiac diseases seem to have a larger impact on overall mortality. METHODS: From
      1997 to 2003, all incident haemodialysis patients in a single centre were
      enrolled in this prospective study. Those with clinical signs of vascular disease
      were examined by coronary or peripheral angiographies. Physicians took the
      patients' medical histories, examined them and followed them up until the end of
      the study or death. Causes of death were defined by the physicians. RESULTS: In
      all, 322 patients were enrolled in the study, 38% of whom were diabetic. At the
      start of dialysis treatment, 38% had coronary artery disease (CAD), defined as
      >50% stenosis of at least one coronary artery or as definite myocardial
      infarction, and 14% had critical ischaemia of at least one limb (CLI). In all
      patients with foot lesions, CLI was defined angiographically, as evidenced by
      stenosis or rarefication of distal vessels in the legs. Patients who died (n =
      121) [due to cardiac causes (n = 25), complications of CLI (n = 22), stroke (n =
      10), cachexia following a long-standing, non-malignant disease (n = 6),
      malignancy (n = 24), infection not related to CLI (n = 18) and other causes (n =
      16)] were older (71+/-10 vs 65+/-13 years), more often male [74/121 (61%)] and
      often diabetic [56/121 (46%)]. CAD was documented in 82/121 (68%). Five-year
      survivals in patients with no risk and diabetes without CAD or CLI, CAD and CLI
      were 74%, 73%, 50% and 10%, respectively. Age, CLI and smoking habits
      independently increased the risk of death (hazard ratios: 1.052, 4.921 and 2.292,
      respectively). CONCLUSIONS: These results indicate that CLI with associated
      complications is not only an indicator of high mortality in patients with ESRD,
      but is also one of the main causes of death.

PMID- 15266036
TI  - Increased response of renal perfusion to the antioxidant vitamin C in type 2
      diabetes.
AB  - BACKGROUND: Reactive oxygen species play a major role in the development of
      endothelial dysfunction. It is as yet unspecified whether increased oxidative
      stress contributes to endothelial dysfunction of the renal vasculature in
      patients with type 2 diabetes. METHODS: Renal haemodynamics were studied in 20
      patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and
      20 non-diabetic hypertensive patients at baseline and following infusions of the
      nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg);
      the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the
      antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg). RESULTS: The
      response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42
      ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73
      m(2); P = NS) was not different between diabetic and non-diabetic patients. In
      contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in
      non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33
      ml/min/1.73 m(2); P<0.05). CONCLUSIONS: The difference in the response of renal
      perfusion to an antioxidant suggests increased formation of reactive oxygen
      species and thereby reduced nitric oxide bioavailability in the renal vasculature
      of patients with type 2 diabetes.

PMID- 15266037
TI  - Factors associated with access blood flow in native vessel arteriovenous
      fistulae.
AB  - BACKGROUND: Access blood flow (Qa) identifies stenosis in patients with native
      vessel AV fistulae (AVF), but data on factors that are associated with Qa in
      normally functioning accesses are sparse. Such factors could be used in
      conjunction with Qa to improve the diagnostic performance of screening. We
      examined the relationship between Qa and certain clinical characteristics in a
      large group of patients with AVF. METHODS: This was a retrospective study of
      incident and prevalent haemodialysis patients treated at a single institution,
      all of whom had a functioning AVF during the study period. Qa was measured
      bimonthly using ultrasound dilution in all subjects. Mixed models were used to
      explore the relationship between Qa and a group of independent variables,
      including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean
      arterial pressure (MAP), diabetes mellitus, patient age, sex, height, body mass
      index (BMI) and AVF location (forearm vs upper arm). RESULTS: A total of 4084 Qa
      measurements was made in 294 patients. Univariate analysis found that younger
      patient age, non-diabetic status, higher blood pressure (SBP, DBP, MAP, all at
      the time of Qa measurement), upper arm AVF location and overweight status (BMI
      >/=25) were significantly associated with Qa. SBP appeared to be more strongly
      associated with Qa than either DBP or MAP. Patient sex, height and interval
      between access creation and Qa measurement were not significantly associated with
      Qa. Tests for interaction suggested that the association between SBP and age and
      Qa varied significantly by access location. In a multivariate model, SBP,
      overweight status and diabetic status were independently associated with Qa. The
      strength of the association between these characteristics and Qa appeared to be
      clinically relevant. CONCLUSIONS: Our findings suggest that a single Qa threshold
      for angiography in all patients may be simplistic, and that the optimal threshold
      might vary by patient subgroup. The strong association between SBP and Qa
      suggests that adjusting Qa for SBP may improve the specificity of access
      screening. Further work is required to determine whether such modifications to
      current practice would improve the predictive power of Qa measurements for
      detection of stenosis in AVF.

PMID- 15266038
TI  - Development and validation of the medication regimen complexity index.
AB  - BACKGROUND: Medication regimen attributes, such as the number of drugs, dosage
      frequency, administration instructions, and the prescribed dosage forms, have
      been shown to influence patient outcomes. No single tool for quantifying the
      complexity of general medication regimens has been published in the medical
      literature. OBJECTIVE: To develop and validate a tool to quantify the complexity
      of prescribed medication regimens. METHODS: Literature findings and the expertise
      of the authors were used for developing the tool. Eight pharmacy researchers
      helped in establishing the tool's face and content validity. The new tool was
      tested on 134 medication regimens from patients with moderate to severe chronic
      obstructive pulmonary disease. Six regimens with a spread of scores on the tool
      were presented to a 5-member expert panel that subjectively ranked these regimens
      to confirm the tool's criterion-related validity. The relationships between
      scores on the tool and various independent variables were tested to judge the
      tool's construct validity. Two raters scored 25 regimens using the tool to test
      its inter-rater and test-retest reliabilities. RESULTS: A 65-item Medication
      Regimen Complexity Index (MRCI) was developed. The expert panel had strong
      agreement (Kendall's W = 0.8; p = 0.001) on their individual rankings of the 6
      regimens. The panel's consensus ranking had perfect correlation with the MRCI
      ranking. The total MRCI score had significant correlation with the number of
      drugs in the regimen (Spearman's Rho = 0.9; p < 0.0001), but not with the age and
      gender of the patients. Inter-rater and test-retest reliabilities for the total
      score and scores for individual sections on the MRCI were > or = 0.9.
      CONCLUSIONS: The MRCI is a reliable and valid tool for quantifying drug regimen
      complexity with potential applications in both practice and research.

PMID- 15266039
TI  - Growth hormone use in children with idiopathic short stature.
AB  - OBJECTIVE: To review the indication, pharmacology, pharmacokinetics, efficacy,
      and adverse effects of recombinant human growth hormone in children with
      idiopathic short stature (ISS). DATA SOURCES: A MEDLINE search (1966-December
      2003) was performed using the key words human growth hormone, somatropin,
      Humatrope, normal children, somatrem, and idiopathic short stature. Food and Drug
      Administration Advisory Committee Meeting minutes were also reviewed. STUDY
      SELECTION AND DATA EXTRACTION: The data presented in this review were obtained
      from published literature, abstracts presented at scientific meetings, and
      information on file with the manufacturer. Additional articles from these sources
      were also identified. Current issues of pediatric and endocrinology journals were
      reviewed for the most recent articles. Articles only addressing the use of growth
      hormone in normal, healthy children were used. DATA SYNTHESIS: Somatropin is
      indicated for use in children with ISS. Studies have shown modest benefit to
      final height achieved and, at the doses used for ISS, there have been no adverse
      effects associated with somatropin. Many questions still exist, however,
      concerning the most appropriate age to initiate treatment and duration of
      treatment. There are also many ethical concerns surrounding patient selection
      criteria and potential for increased off-label use. CONCLUSIONS: Growth hormone
      has been found to have modest efficacy in improving final height in children with
      ISS. The specific patient population likely to achieve maximal benefit, optimal
      dosage regimens, and the long-term adverse effects of extended duration of
      therapy are unknown.

PMID- 15266040
TI  - Cholestatic attack due to ampicillin and cross-reactivity to cefuroxime.

PMID- 15266041
TI  - Second-generation thiazolidinediones and hepatotoxicity.
AB  - OBJECTIVE: To report a case of hepatotoxicity probably caused by pioglitazone,
      summarize case reports of hepatotoxicity induced by rosiglitazone or
      pioglitazone, and make recommendations regarding routine liver enzyme measurement
      in patients taking these agents. CASE SUMMARY: A 39-year-old black woman with
      type 2 diabetes mellitus, hypertension, and congestive heart failure presented to
      a pharmacist-staffed diabetes comanagement service. She reported fatigue, dark
      brown urine, nausea, itching, and loss of appetite. Pioglitazone was promptly
      discontinued because her symptoms were consistent with those of hepatic
      dysfunction and pioglitazone was identified as a potential cause. The patient was
      referred to her physician. Liver enzyme levels were checked 13 days after initial
      presentation and found to be abnormal: alanine aminotransferase 490 U/L,
      aspartate aminotransferase 360 U/L, alkaline phosphatase 851 U/L, total bilirubin
      3.1 mg/dL, direct bilirubin 2.0 mg/dL, and indirect bilirubin 1.1 mg/dL. Within
      2(1/2) months of discontinuing pioglitazone, the patient's symptoms resolved and
      liver enzyme levels returned to normal. DISCUSSION: Troglitazone, a
      thiazolidinedione (TZD), was removed from the market because of hepatotoxicity.
      Reported cases involving the newer TZDs, rosiglitazone and pioglitazone, have
      been few in number and less severe in consequence. Six cases of rosiglitazone
      induced hepatotoxicity and 5 of pioglitazone-induced hepatotoxicity have been
      reported. Most patients improved symptomatically 2-4 weeks following
      discontinuation of the offending TZD, with normalization of liver enzyme levels
      in 2 weeks to 6 months following TZD discontinuation. CONCLUSIONS: Although the
      timeline and extent of liver enzyme elevation in this case are unclear, the
      Naranjo probability scale suggests that a causal relationship between
      pioglitazone and liver disease is probable. Patients with previous TZD-induced
      hepatotoxicity should not be rechallenged. Cases of hepatotoxicity with second
      generation TZDs, although clearly linked, have been few in number and less severe
      in consequence when compared to troglitazone. We agree with current package
      labeling that requires baseline and then periodic measurement of liver enzymes in
      patients taking pioglitazone or rosiglitazone.

PMID- 15266042
TI  - Severe acquired hemophilia with factor VIII inhibition associated with
      acetaminophen and chlorpheniramine.
AB  - OBJECTIVE: To report a case of acquired hemophilia with a high-titer factor VIII
      inhibitor associated with the use of acetaminophen and chlorpheniramine in
      combination. CASE SUMMARY: An 83-year-old woman presented with a severe bleeding
      disorder 2 weeks after she was prescribed acetaminophen and chlorpheniramine for
      treatment of a flu-like illness. Laboratory studies showed severe anemia with
      greatly reduced factor VIII activity and the presence of a high-titer factor VIII
      inhibitor at 228 Bethesda units. Treatment with high-dose corticosteroids,
      transfusion of several units of red blood cells, and repeated infusions of factor
      VIII bypassing activity was successful. Complete clinical and laboratory
      remission was achieved after 4 weeks of treatment. Use of the Naranjo probability
      scale suggested a possible association between this adverse event and treatment
      with acetaminophen and chlorpheniramine. DISCUSSION: Acquired hemophilia due to
      factor VIII inhibitor(s) has been associated with the use of drugs such as
      thioxanthenes, interferon, and fludarabine. As of this writing, to the best of
      our knowledge, no other case has been reported among patients receiving
      acetaminophen or chlorpheniramine. CONCLUSIONS: We suggest that acquired
      hemophilia due to factor VIII inhibitor(s) should be considered in the
      appropriate setting when patients present with unexplained and even minor
      bleeding while on treatment with acetaminophen or chlorpheniramine alone or
      combined.

PMID- 15266043
TI  - Is the Naranjo probability scale accurate enough to ascertain causality in drug
      induced hepatotoxicity?

PMID- 15266044
TI  - Clinical and economic analysis of methicillin-susceptible and -resistant
      Staphylococcus aureus infections.
AB  - BACKGROUND: The rate of methicillin-resistant Staphylococcus aureus (MRSA) has
      increased significantly over the last decade. Previous cohort studies of patients
      with MRSA bacteremia have reported higher mortality rates, increased morbidity,
      longer hospital length of stay (LOS), and higher costs compared with patients
      with methicillin-susceptible S. aureus (MSSA) bacteremia. The clinical and
      economic impact of MRSA involving other sites of infection has not been well
      characterized. OBJECTIVE: To determine the clinical and economic implications of
      MRSA compared with MSSA infections across a variety of infection sites and
      severity of illnesses. METHODS: A retrospective, case-control analysis comparing
      differences in clinical and economic outcomes of patients with MRSA and MSSA
      infections was conducted at an academic medical center. Case patients with MRSA
      infection were matched (1:1 ratio) to control patients with MSSA infection
      according to age, site of infection, and type of care. RESULTS: Thirty-six
      matched pairs of patients with S. aureus infection were identified. Baseline
      characteristics of patients with MSSA and MRSA infection were similar. Patients
      with MRSA infections had a trend toward longer hospital LOS (15.5 vs 11 days; p =
      0.05) and longer antibiotic-related LOS (10 vs 7 days; p = 0.003). Median
      hospital cost associated with treatment of patients with MRSA infections was
      higher compared with patients with MSSA infections ($16,575 vs $12,862; p =
      0.11); however, this difference was not statistically significant. Treatment
      failure was common in patients with MRSA infection. Among patients with MSSA
      infections, treatment failure was associated with vancomycin use. CONCLUSIONS:
      Patients with MRSA infections had worse clinical and economic outcomes compared
      with patients with MSSA infections.

PMID- 15266045
TI  - Lack of pharmacokinetic or pharmacodynamic interaction between memantine and
      donepezil.
AB  - BACKGROUND: Memantine, a low- to moderate-affinity, uncompetitive N-methyl-D
      aspartate receptor antagonist, was approved in the US for treatment of moderate
      to severe Alzheimer's disease in October 2003. OBJECTIVE: To determine whether an
      in vivo pharmacokinetic interaction exists between memantine and the
      acetylcholinesterase (AChE) inhibitor donepezil. METHODS: In this open-label,
      multiple-dose study, 24 healthy subjects (aged 18-35 y) received oral
      administration of memantine 10 mg on day 1. Following a 14-day washout period,
      subjects were orally administered donepezil 5 mg once daily for 7 days on an
      outpatient basis. Beginning on day 22, the donepezil dosage was doubled for 22
      days to the target dose of 10 mg once daily, with the last donepezil dose
      concomitantly administered with memantine 10 mg on day 43. Assessments included
      pharmacokinetic as well as safety parameters. In addition, AChE inhibition was
      measured in red blood cells by radiolabeled-enzyme assay following administration
      of donepezil alone and after a single memantine dose. RESULTS: Data from 19
      subjects who completed the study indicated no significant pharmacokinetic
      interactions between a single dose of memantine and multiple doses of donepezil.
      Percent maximum inhibition of AChE activity (mean +/- SD) by donepezil was 77.8
      +/- 7.3% and not significantly different upon coadministration of a single dose
      of memantine (81.1 +/- 5.7%). Two subjects withdrew due to adverse events while
      taking donepezil alone. Single memantine doses administered with multiple
      donepezil doses were well tolerated. CONCLUSIONS: The pharmacokinetic and
      pharmacodynamic data from this study indicated a lack of interaction between
      memantine and donepezil, suggesting that memantine and donepezil may be safely
      and effectively used in combination.

PMID- 15266046
TI  - Research in children: assessing risks and benefits.

PMID- 15266047
TI  - Quantitative trait locus dissection in congenic strains of the Goto-Kakizaki rat
      identifies a region conserved with diabetes loci in human chromosome 1q.
AB  - Genetic studies in human populations and rodent models have identified regions of
      human chromosome 1q21-25 and rat chromosome 2 showing evidence of significant and
      replicated linkage to diabetes-related phenotypes. To investigate the
      relationship between the human and rat diabetes loci, we fine mapped the rat
      locus Nidd/gk2 linked to hyperinsulinemia in an F2 cross derived from the
      diabetic (type 2) Goto-Kakizaki (GK) rat and the Brown Norway (BN) control rat,
      and carried out its genetic and pathophysiological characterization in BN.GK
      congenic strains. Evidence of glucose intolerance and enhanced insulin secretion
      in a congenic strain allowed us to localize the underlying diabetes gene(s) in a
      rat chromosomal interval of approximately 3-6 cM conserved with an 11-Mb region
      of human 1q21-23. Positional diabetes candidate genes were tested for
      transcriptional changes between congenics and controls and sequence variations in
      a panel of inbred rat strains. Congenic strains of the GK rats represent powerful
      novel models for accurately defining the pathophysiological impact of diabetes
      gene(s) at the locus Nidd/gk2 and improving functional annotations of diabetes
      candidates in human 1q21-23.

PMID- 15266050
TI  - Ice-cap. A high-throughput method for capturing plant tissue samples for genotype
      analysis.
AB  - High-throughput genotype screening is rapidly becoming a standard research tool
      in the post-genomic era. A major bottleneck currently exists, however, that
      limits the utility of this approach in the plant sciences. The rate-limiting step
      in current high-throughput pipelines is that tissue samples from living plants
      must be collected manually, one plant at a time. In this article I describe a
      novel method for harvesting tissue samples from living seedlings that eliminates
      this bottleneck. The method has been named Ice-Cap to reflect the fact that ice
      is used to capture the tissue samples. The planting of seeds, growth of
      seedlings, and harvesting of tissue are all performed in a 96-well format. I
      demonstrate the utility of this system by using tissue harvested by Ice-Cap to
      genotype a population of Arabidopsis seedlings that is segregating a previously
      characterized mutation. Because the harvesting of tissue is performed in a
      nondestructive manner, plants with the desired genotype can be transferred to
      soil and grown to maturity. I also show that Ice-Cap can be used to analyze
      genomic DNA from rice (Oryza sativa) seedlings. It is expected that this method
      will be applicable to high-throughput screening with many different plant
      species, making it a useful technology for performing marker assisted selection.

PMID- 15266049
TI  - Endocytosis, actin cytoskeleton, and signaling.

PMID- 15266051
TI  - Activity profiling of papain-like cysteine proteases in plants.
AB  - Transcriptomic and proteomic technologies are generating a wealth of data that
      are frequently used by scientists to predict the function of proteins based on
      their expression or presence. However, activity of many proteins, such as
      transcription factors, kinases, and proteases, depends on posttranslational
      modifications that frequently are not detected by these technologies. Therefore,
      to monitor activity of proteases rather than their abundance, we introduce
      protease activity profiling in plants. This technology is based on the use of
      biotinylated, irreversible protease inhibitors that react with active proteases
      in a mechanism-based manner. Using a biotinylated derivative of the Cys protease
      inhibitor E-64, we display simultaneous activities of many papain-like Cys
      proteases in extracts from various tissues and from different plant species.
      Labeling is pH dependent, stimulated with reducing agents, and inhibited
      specifically by Cys protease inhibitors but not by inhibitors of other protease
      classes. Using one-step affinity capture of biotinylated proteases followed by
      sequencing mass spectrometry, we identified proteases that include xylem-specific
      XCP2, desiccation-induced RD21, and cathepsin B- and aleurain-like proteases.
      Together, these results demonstrate that this technology can identify
      differentially activated proteases and/or characterize the activity of a
      particular protease within complex mixtures.

PMID- 15266052
TI  - Computational identification and characterization of novel genes from legumes.
AB  - The Fabaceae, the third largest family of plants and the source of many crops,
      has been the target of many genomic studies. Currently, only the grasses surpass
      the legumes for the number of publicly available expressed sequence tags (ESTs).
      The quantity of sequences from diverse plants enables the use of computational
      approaches to identify novel genes in specific taxa. We used BLAST algorithms to
      compare unigene sets from Medicago truncatula, Lotus japonicus, and soybean
      (Glycine max and Glycine soja) to nonlegume unigene sets, to GenBank's
      nonredundant and EST databases, and to the genomic sequences of rice (Oryza
      sativa) and Arabidopsis. As a working definition, putatively legume-specific
      genes had no sequence homology, below a specified threshold, to publicly
      available sequences of nonlegumes. Using this approach, 2,525 legume-specific EST
      contigs were identified, of which less than three percent had clear homology to
      previously characterized legume genes. As a first step toward predicting
      function, related sequences were clustered to build motifs that could be searched
      against protein databases. Three families of interest were more deeply
      characterized: F-box related proteins, Pro-rich proteins, and Cys cluster
      proteins (CCPs). Of particular interest were the >300 CCPs, primarily from
      nodules or seeds, with predicted similarity to defensins. Motif searching also
      identified several previously unknown CCP-like open reading frames in
      Arabidopsis. Evolutionary analyses of the genomic sequences of several CCPs in M.
      truncatula suggest that this family has evolved by local duplications and
      divergent selection.

PMID- 15266053
TI  - Development of genome-wide DNA polymorphism database for map-based cloning of
      rice genes.
AB  - DNA polymorphism is the basis to develop molecular markers that are widely used
      in genetic mapping today. A genome-wide rice (Oryza sativa) DNA polymorphism
      database has been constructed in this work using the genomes of Nipponbare, a
      cultivar of japonica, and 93-11, a cultivar of indica. This database contains
      1,703,176 single nucleotide polymorphisms (SNPs) and 479,406 Insertion/Deletions
      (InDels), approximately one SNP every 268 bp and one InDel every 953 bp in rice
      genome. Both SNPs and InDels in the database were experimentally validated. Of
      109 randomly selected SNPs, 107 SNPs (98.2%) are accurate. PCR analysis indicated
      that 90% (97 of 108) of InDels in the database could be used as molecular
      markers, and 68% to 89% of the 97 InDel markers have polymorphisms between other
      indica cultivars (Guang-lu-ai 4 and Long-te-pu B) and japonica cultivars (Zhong
      hua 11 and 9522). This suggests that this database can be used not only for
      Nipponbare and 93-11, but also for other japonica and indica cultivars. While
      validating InDel polymorphisms in the database, a set of InDel markers with each
      chromosome 3 to 5 marker was developed. These markers are inexpensive and easy to
      use, and can be used for any combination of japonica and indica cultivars used in
      this work. This rice DNA polymorphism database will be a valuable resource and
      important tool for map-based cloning of rice gene, as well as in other various
      research on rice (http://shenghuan.shnu.edu.cn/ricemarker).

PMID- 15266054
TI  - Identification of genes required for embryo development in Arabidopsis.
AB  - A long-term goal of Arabidopsis research is to define the minimal gene set needed
      to produce a viable plant with a normal phenotype under diverse conditions. This
      will require both forward and reverse genetics along with novel strategies to
      characterize multigene families and redundant biochemical pathways. Here we
      describe an initial dataset of 250 EMB genes required for normal embryo
      development in Arabidopsis. This represents the first large-scale dataset of
      essential genes in a flowering plant. When compared with 550 genes with other
      knockout phenotypes, EMB genes are enriched for basal cellular functions,
      deficient in transcription factors and signaling components, have fewer paralogs,
      and are more likely to have counterparts among essential genes of yeast
      (Saccharomyces cerevisiae) and worm (Caenorhabditis elegans). EMB genes also
      represent a valuable source of plant-specific proteins with unknown functions
      required for growth and development. Analyzing such unknowns is a central
      objective of genomics efforts worldwide. We focus here on 34 confirmed EMB genes
      with unknown functions, demonstrate that expression of these genes is not embryo
      specific, validate a strategy for identifying interacting proteins through
      complementation with epitope-tagged proteins, and discuss the value of EMB genes
      in identifying novel proteins associated with important plant processes. Based on
      sequence comparison with essential genes in other model eukaryotes, we identify
      244 candidate EMB genes without paralogs that represent promising targets for
      reverse genetics. These candidates should facilitate the recovery of additional
      genes required for seed development.

PMID- 15266055
TI  - Metabolic responses to the reduction in palmitate caused by disruption of the
      FATB gene in Arabidopsis.
AB  - Disruption of the FATB gene in Arabidopsis results in a two-thirds reduction in
      saturated fatty acids, largely palmitate, in the leaf extra-plastidic
      phospholipids and a reduction in the growth rate of the mutant compared to wild
      type (Bonaventure G, Salas JJ, Pollard MR, Ohlrogge JB [2003] Plant Cell 15: 1020
      1033). In this study, we report that although fatb-ko seedlings grow more slowly
      than wild type, the rate of fatty acid synthesis in leaves of the mutant
      increases by 40%. This results in approximately the same amount of palmitate
      exported from the plastid as in wild type but an increase in oleate export of
      about 55%. To maintain constant amounts of fatty acids in leaves, thereby
      counterbalancing their higher rate of production, the mutant also increases its
      rate of fatty acid degradation. Although fatb-ko leaves have higher rates of
      fatty acid synthesis and turnover, the relative proportions of membrane lipids
      are similar to wild type. Thus, homeostatic mechanisms to preserve membrane
      compositions compensate for substantial changes in rates of fatty acid and
      glycerolipid metabolism in the mutant. Pulse-chase labeling studies show that in
      fatb-ko leaves there is a net increase in the synthesis of both prokaryotic and
      eukaryotic lipids and consequently of their turnover. The net loss of palmitate
      from phosphatidylcholine plus phosphatidylethanolamine is similar for wild type
      and mutant, suggesting that mechanisms are not present that can preferentially
      preserve the saturated fatty acids. In summary, the leaf cell responds to the
      loss of saturated fatty acid production in the fatb-ko mutant by increasing both
      fatty acid synthesis and degradation, but in doing so the mechanisms for
      increased fatty acid turnover contribute to the lowering of the percentage of
      saturated fatty acids found in eukaryotic lipids.

PMID- 15266056
TI  - Characterization of Arabidopsis glutamine phosphoribosyl pyrophosphate
      amidotransferase-deficient mutants.
AB  - Using a transgene-based screening, we previously isolated several Arabidopsis
      mutants defective in protein import into chloroplasts. Positional cloning of one
      of the loci, CIA1, revealed that CIA1 encodes Gln phosphoribosyl pyrophosphate
      amidotransferase 2 (ATase2), one of the three ATase isozymes responsible for the
      first committed step of de novo purine biosynthesis. The cia1 mutant had normal
      green cotyledons but small and albino/pale-green mosaic leaves. Adding AMP, but
      not cytokinin or NADH, to plant liquid cultures partially complemented the mutant
      phenotypes. Both ATase1 and ATase2 were localized to chloroplasts. Overexpression
      of ATase1 fully complemented the ATase2-deficient phenotypes. A T-DNA insertion
      knockout mutant of the ATase1 gene was also obtained. The mutant was
      indistinguishable from the wild type. A double mutant of cia1/ATase1-knockout had
      the same phenotype as cia1, suggesting at least partial gene redundancy between
      ATase1 and ATase2. Characterizations of the cia1 mutant revealed that mutant
      leaves had slightly smaller cell size but only half the cell number of wild-type
      leaves. This phenotype confirms the role of de novo purine biosynthesis in cell
      division. Chloroplasts isolated from the cia1 mutant imported proteins at an
      efficiency less than 50% that of wild-type chloroplasts. Adding ATP and GTP to
      isolated mutant chloroplasts could not restore the import efficiency. We conclude
      that de novo purine biosynthesis is not only important for cell division, but
      also for chloroplast biogenesis.

PMID- 15266057
TI  - Expression in multigene families. Analysis of chloroplast and mitochondrial
      proteases.
AB  - The proteolytic machinery of chloroplasts and mitochondria in Arabidopsis
      consists primarily of three families of ATP-dependent proteases, Clp, Lon, and
      FtsH, and one family of ATP-independent proteases, DegP. However, the functional
      significance of the multiplicity of their genes is not clear. To test whether
      expression of specific isomers could be differently affected by growth
      conditions, we analyzed transcript abundance following short-term exposure to
      different environmental stimuli, using 70-mer oligonucleotide arrays. This
      analysis revealed variability in the response to high light and different
      temperatures within members of each family. Thirty out of the 41 tested genes
      were up-regulated in response to high light, including both chloroplast and
      mitochondrial isozymes, whereas only six and five genes responded to either high
      or low temperature, respectively. The extent of response was variable, ranging
      from 2- to 20-fold increase in the steady-state levels. Absolute transcript
      levels of the tested genes, compiled from one-channel arrays, were also variable.
      In general, transcripts encoding mitochondrial isozymes were accumulated to a
      lower level than chloroplastic ones. Within the FtsH family, transcript abundance
      of most genes correlated with the severity of mutant phenotypes in the relevant
      genes. This correlation was also evident at the protein level. Analysis of FtsH
      isozymes revealed that FtsH2 was the most abundant species, followed by FtsH5 and
      8, with FtsH1 being accumulated to only 10% of FtsH2 level. These results suggest
      that, unlike previous expectations, the relative importance of different
      chloroplast protease isozymes, evidenced by mutant phenotypes at least in the
      FtsH family, is determined by their abundance, and not necessarily by different
      specific functions or specialized expression under certain conditions.

PMID- 15266058
TI  - Central role for liver X receptor in insulin-mediated activation of Srebp-1c
      transcription and stimulation of fatty acid synthesis in liver.
AB  - Transcription of the gene encoding sterol regulatory element-binding protein 1c
      (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP
      1c protein activates transcription of the genes required for fatty acid
      synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the
      mechanism of insulin activation in freshly isolated rat hepatocytes. The data
      show that a complete insulin response (increase of 6- to 11-fold) requires two
      binding sites for liver X receptors (LXRs), which are nuclear receptors that are
      activated by oxygenated sterols. Disruption of these binding sites did not lower
      basal transcription but severely reduced the response to insulin. In contrast,
      disruption of the closely linked binding sites for SREBPs and nuclear factor Y
      lowered basal transcription drastically but still permitted a 4- to 7-fold
      increase in response to insulin. Arachidonic acid, an inhibitor of LXR
      activation, blocked the response to insulin. We conclude that insulin activates
      the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly
      through production of a ligand that activates LXRs or their heterodimerizing
      partner, the retinoid X receptor. Nuclear SREBPs and nuclear factor Y play
      permissive roles.

PMID- 15266059
TI  - Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic
      sclerosis.
AB  - OBJECTIVE: To determine serum levels of soluble cytotoxic T-lymphocyte associated
      molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis
      (SSc). METHODS: Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc
      (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme
      linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30
      SSc patients were analysed (follow-up 2.1-7.0 yr). RESULTS: Serum sCTLA-4 levels
      were elevated in dSSc patients compared with normal controls (n = 41), lSSc
      patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By
      contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients
      with elevated sCTLA-4 levels had a shorter disease duration and more frequent
      presence of digital pitting scars, contracture of phalanges, diffuse
      pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC)
      than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with
      the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody
      levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with
      improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not
      improve in two of six dSSc patients with high sCTLA-4 levels throughout the
      follow-up, while the remaining four patients showed improvement of skin
      sclerosis. CONCLUSION: These results suggest that sCTLA-4 correlates with disease
      severity and activity of SSc and that sCTLA-4 plays a role in immunological
      abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well
      as T-cell responses by interfering with B7-CTLA-4 interactions that induce
      negative signals in T and B cells.

PMID- 15266060
TI  - Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact?
AB  - OBJECTIVES: Serum prolactin concentrations have been reported as higher, similar
      or lower in patients with rheumatoid arthritis (RA) compared with control
      subjects. We investigated whether low biological activity macroprolactin (a
      prolactin antibody complex), which is detected variably in different prolactin
      immunoassays, could account for the discrepant total prolactin results reported
      in RA. METHODS: We compared serum total prolactin and free prolactin in 60 women
      with RA and 31 female controls. RESULTS: No subject had hyperprolactinaemia or
      macroprolactinaemia. Serum concentrations of total and free (monomeric) prolactin
      were higher (P<0.05) in women with RA [mean (s.d.), 225.6 (104.6) and 201.6
      (95.4) mU/l respectively] compared with controls [175.0 (68.5) and 154.0 (60.9)
      mU/l respectively]. CONCLUSIONS: We report higher serum free prolactin
      concentrations in women with RA compared with control subjects. This result
      indicates that the higher serum total prolactin levels in patients with RA are
      the consequence of increased free prolactin concentrations and are not due to
      macroprolactin.

PMID- 15266061
TI  - Gout and alcohol.

PMID- 15266062
TI  - Different cytokine profiles in patients with chronic and acute reactive
      arthritis.
AB  - OBJECTIVE: Analysis of cytokine production in patients with acute and chronic
      reactive arthritis (AcReA/ChrReA) in order to search for new treatment
      possibilities. METHODS: Cytokine production by peripheral blood and synovial
      fluid mononuclear cells (PBMCs/SFMCs) of 28 patients with AcReA, 27 patients with
      ChrReA, 26 patients with rheumatoid arthritis (RA) and 31 healthy controls was
      analysed by enzyme-linked immunosorbent assay (ELISA) and flow-cytometry.
      Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma) and interleukin (IL)-10 was measured by ELISA, while the percentages of
      TNF-alpha-, IFN-gamma- and IL-4-positive CD3+ cells were determined in the same
      groups of patients and healthy subjects using flow cytometry. RESULTS:
      Spontaneous TNF-alpha production observed in PBMCs of ChrReA, but not of AcReA,
      patients was significantly higher (P<0.001) than in healthy controls. The
      percentages of TNF-alpha-positive CD3+ blood cells in ChrReA exceeded that of RA
      patients and healthy controls (P<0.05 and P<0.001, respectively). Also, the
      percentages of IFN-gamma-positive CD3+ cells were significantly higher in
      peripheral blood and synovial fluid of ChrReA patients (P<0.05 and P<0.05,
      respectively) as compared with AcReA. In ChrReA spontaneous IL-10 production in
      PBMCs was similar to that observed in healthy controls, while in RA and AcReA the
      production of IL-10 was significantly increased (P<0.05 and P<0.05,
      respectively). IL-4 production was low in all study groups with no significant
      differences detected. CONCLUSIONS: High production of TNF-alpha and IFN-gamma
      detected in ChrReA supports the possible use of anti-TNF-alpha treatment in
      ChrReA.

PMID- 15266063
TI  - Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus:
      a possible alternative.
AB  - OBJECTIVE: To determine the efficacy of tacrolimus ointment 0.1% on resistant
      cutaneous lesions in patients with lupus erythematosus. METHODS: Twelve patients
      with skin manifestations were studied. Six had discoid lupus (DL), four subacute
      cutaneous lupus erythematosus (SCLE) and two systemic lupus erythematosus (SLE).
      All patients had extensive skin lesions refractory to previous treatment.
      Patients received topical tacrolimus 0.1% for a minimum of 6 weeks and response
      was evaluated by physicians' and patients' assessment and documented with
      photographs at baseline and at the end of the treatment. RESULTS: Eleven of 12
      patients completed the therapy. One patient with DL discontinued because of side-
      effects-peeling and a burning sensation. Six patients were clearly improved, one
      patient had a minor remission of his face lesion while in four the rashes
      remained the same. Two patients with SCLE had significant regression of their
      lesions while the other two had no improvement. In DL, two had certain
      improvement, one minor improvement and two were without response. The patients
      with SLE had significant amelioration of their extensive photosensitive rash.
      CONCLUSION: Tacrolimus ointment 0.1% may be an effective alternative in patients
      with severe resistant cutaneous manifestations in lupus erythematosus.

PMID- 15266064
TI  - Chronic periaortitis.
AB  - Chronic periaortitis commonly involves the infrarenal portion of the abdominal
      aorta. Idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic
      aneurysm and perianeurysmal retroperitoneal fibrosis are its various clinical
      presentations. They present as a non-specific systemic inflammatory disorder and
      may lead to ureteric obstruction and consequent renal failure. An exaggerated
      inflammatory response to advanced atherosclerosis has been thought to be the main
      pathogenetic process. Autoimmunity has also been proposed as a contributing
      factor. Contrast-enhanced CT scanning is the diagnostic test of choice. Steroids
      and immunosuppressive agents are successfully used in the treatment of idiopathic
      retroperitoneal fibrosis and selected cases of inflammatory abdominal aortic
      aneurysm, and surgery is used in others. Early diagnosis is important in order to
      reduce morbidity from complications such as renal failure and mortality from
      aortic rupture.

PMID- 15266065
TI  - Patient education for diverse populations.

PMID- 15266066
TI  - Activity concentrations and mean annual effective dose of foodstuffs on the
      island of Tenerife, Spain.
AB  - A total of 26 different food types and 12 elaborated diets were analysed by low
      level gamma spectrometry to measure their content of 238U(234Th), 228Ra(228Ac),
      226Ra(214Pb), 210Pb, 137Cs and 40K. The concentrations of these radionuclides
      measured in some imported foodstuffs were compared with those measured in some
      locally produced ones. Moreover, the concentrations found in the analysed
      foodstuffs and composite diets were compared with the data available in
      literature from other locations, such as Egypt, Brazil, Poland and Hong Kong. 40K
      contributed highest to the daily dose produced by the intake of comestibles. The
      largest 40K concentrations were measured in the chickpeas and beans with 380 +/-
      30 and 380 +/- 20 Bq kg(-1) fresh weights, respectively. The artificial
      radionuclide 137Cs was measured only above detection limits in the potatoes and
      sweet potatoes. A mean annual effective dose of 362 microSv with a standard
      deviation of 110 microSv was calculated from the composite diets.

PMID- 15266067
TI  - Assessment of occupational exposure to radiofrequency fields and radiation.
AB  - The use of personal monitors for the assessment of exposure to radiofrequency
      fields and radiation in potential future epidemiological studies of
      occupationally exposed populations has been investigated. Data loggers have been
      developed for use with a commercially available personal monitor and these
      allowed personal exposure records consisting of time-tagged measurements of
      electric and magnetic field strength to be accrued over extended periods of the
      working day. The instrumentation was worn by workers carrying out tasks
      representative of some of their typical daily activities at a variety of radio
      sites. The results indicated significant differences in the exposures of workers
      in various RF environments. A number of measures of exposure have been examined
      with a view to assessing possible exposure metrics for epidemiological studies.
      There was generally a good correlation between a given measure of electric field
      strength and the same measure of magnetic field strength.

PMID- 15266068
TI  - Assessment of aircrew radiation exposure by further measurements and model
      development.
AB  - A methodology is presented for collecting and analysing exposure measurements
      from galactic cosmic radiation using a portable equipment suite and encapsulating
      these data into a semi-empirical model/Predictive Code for Aircrew Radiation
      Exposure (PCAIRE) for the assessment of aircrew radiation exposure on any flight
      over the solar cycle. The PCAIRE code has been validated against integral route
      dose measurements at commercial aircraft altitudes during experimental flights
      made by various research groups over the past 5 y with code predictions typically
      within +/-20% of the measured data. An empirical correlation, based on ground
      level neutron monitoring data, is detailed further for estimation of aircrew
      exposure from solar particle events. The semi-empirical models have been applied
      to predict the annual and career exposure of a flight crew member using actual
      flight roster data, accounting for contributions from galactic radiation and
      several solar energetic-particle events over the period 1973-2002.

PMID- 15266069
TI  - Radiation exposure assessment for portsmouth naval shipyard health studies.
AB  - Occupational radiation exposures of 13,475 civilian nuclear shipyard workers were
      investigated as part of a retrospective mortality study. Estimates of annual,
      cumulative and collective doses were tabulated for future dose-response analysis.
      Record sets were assembled and amended through range checks, examination of
      distributions and inspection. Methods were developed to adjust for administrative
      overestimates and dose from previous employment. Uncertainties from doses below
      the recording threshold were estimated. Low-dose protracted radiation exposures
      from submarine overhaul and repair predominated. Cumulative doses are best
      approximated by a hybrid log-normal distribution with arithmetic mean and median
      values of 20.59 and 3.24 mSv, respectively. The distribution is highly skewed
      with more than half the workers having cumulative doses <10 mSv and >95% having
      doses <100 mSv. The maximum cumulative dose is estimated at 649.39 mSv from 15
      person-years of exposure. The collective dose was 277.42 person-Sv with 96.8%
      attributed to employment at Portsmouth Naval Shipyard.

PMID- 15266070
TI  - Measured proton sensitivities of bubble detectors.
AB  - The neutron dose equivalent in aircraft is measured using commercial bubble
      detectors, but at high altitudes there are not only neutrons but also protons.
      Bubble detectors have been used because they are considered not to be sensitive
      to protons, but this has been the subject of only a few studies. In this study,
      by irradiating bubble detectors with energetic protons, the detectors' responses
      to protons were observed. Bubbles were clearly formed by protons, but the proton
      sensitivities were one order of magnitude smaller than the neutron sensitivities.
      Thus, counts of protons can be ignored in neutron measurements in aircraft.

PMID- 15266071
TI  - Evaluation of indoor gamma radiation dose in dwellings.
AB  - The use of materials containing naturally occurring radionuclides for house
      construction may enhance the natural radiation background to which some
      population groups are exposed. External exposure results from gamma emitter
      radionuclides existing in the walls, floor and ceiling. Mathematical models can
      be used to predict external dose rates inside a room, provided the compartment
      geometry and the radionuclide concentration activities are known. This paper
      presents a methodology and a computer code for theoretical evaluation of indoor
      external gamma doses in the air. The room was modelled as three pairs of
      rectangular slabs of finite thickness. Doses were evaluated by applying a photon
      transport model, taking into account self-absorption and radiation build-up.
      Calculations were performed for 40K, 226Ra and 232Th, considering concrete walls.
      The results obtained show good agreement with those reported in the literature.
      Dose conversion factors are presented in a practical manner, ready to use for
      radiological impact screening.

PMID- 15266072
TI  - Natural radioactivity measurements in beach-rock samples of south-east coast of
      Tamilnadu, India.
AB  - The concentration of primordial radionuclides in beach-rock samples of the south
      east coast of Tamilnadu, India has been measured using gamma ray spectrum of
      rock. The mean activities of 232Th, 238U and 40K are 144.18, 29.25 and 267.48 Bq
      kg(-1) respectively. In situ measurements were also carried out using
      environmental radiation dosemeter. The linear correlation coefficient was
      obtained. The average activity of concentration of 232Th in the present study is
      2.5 times higher than the world median value while the activity of 238U and 40K
      were found to be lower. This may be due to the heavy minerals present in the
      study area. In the present study, the calculated activity ratio (Th/U) is higher
      than the crustal rocks. This may be due to changes in the crustal composition
      through time (mafic to felsic) that are reflected by a change in the Th and U
      abundances in sedimentary rocks, and also increase in carbon content with time
      resulted in the decrease in U content and increase in Th/U ratio.

PMID- 15266073
TI  - Developing a virtual reality application for training nuclear power plant
      operators: setting up a database containing dose rates in the refuelling plant.
AB  - Operators in Nuclear Power Plants can receive high doses during refuelling
      operations. A training programme for simulating refuelling operations will be
      useful in reducing the doses received by workers as well as minimising operation
      time. With this goal in mind, a virtual reality application is developed within
      the framework of the CIPRES project. The application requires doses, both
      instantaneous and accumulated, to be displayed at all times during operator
      training. Therefore, it is necessary to set up a database containing dose rates
      at every point in the refuelling plant. This database is based on radiological
      protection surveillance data measured in the plant during refuelling operations.
      Some interpolation routines have been used to estimate doses through the
      refuelling plant. Different assumptions have been adopted in order to perform the
      interpolation and obtain consistent data. In this paper, the procedures developed
      to set up the dose database for the virtual reality application are presented and
      analysed.

PMID- 15266074
TI  - Biological estimates of dose to inhabitants of Belarus and Ukraine following the
      Chernobyl accident.
AB  - The purpose of this paper is to investigate how well various assays on blood can
      detect radiation dose to people exposed many years previously and, if possible,
      to estimate that dose. The assays were applied to persons resident close to
      Chernobyl in 1986. Blood samples were taken 13-15 years after the reactor
      accident. The assays used were the frequencies of lymphocyte chromosomal
      translocations, micronuclei, HPRT mutations and apoptotic cells. Translocation
      yields in the exposed groups were marginally higher than in their respective
      controls, leading to dose estimates of about 0.2 Gy but with large uncertainties.
      All other assays showed inconsistency from person to person or other variations
      apparently not related to dose. The measurement of translocations, it is
      concluded, is the biological method of choice for retrospective dosimetry.

PMID- 15266075
TI  - Measurements of environmental terrestrial gamma radiation average dose rate in
      three mountainous locations in the western region of Saudi Arabia.
AB  - This paper describes measurements of external gamma radiation average dose rate
      from terrestrial gamma rays 1 m above the ground in three different mountainous
      locations in the western region of the Kingdom of Saudi Arabia. These locations
      are, At-Taif city, Al-Hada village and Ash-Shafa village. CaSO(4):Dy (TLD-900)
      thermoluminescence dosemeters were used for the detection of terrestrial gamma
      radiation at 40 different places in the three locations. The values of
      terrestrial gamma radiation average dose rate measured ranged between 14 and 279
      nG h(-1) for the time interval from June 2001 to June 2002. The measured average
      dose rate varied with the season of the year. The gamma radiation average dose
      rates were 468, 541 and 781 microGy y(-1) for At-Taif city, Al-Hada village and
      Ash-Shafa village, respectively. The corresponding average effective dose rates
      for the three locations were 94, 108 and 156 microSv y(-1), respectively.

PMID- 15266076
TI  - Methodology study on evaluation of radon flux from soil in China.
AB  - Radon flux rate from soil is one of the most important factors for the evaluation
      of environmental radon levels. The objective of our study is to make a rough
      estimation of the nationwide radon flux rate from soil in China. Considering the
      applicability to the large area and complex distribution of soil types in China,
      a simple model was established. To test the model, field measurements on radon
      flux rate totally in 47 points from different areas were carried out from spring
      to summer in 2003. Laboratory experiments of each soil sample on related soil
      properties, such as radium contents, water contents, soil dry bulk density and
      soil texture were performed simultaneously. Approximately 30% of the samples had
      very consistent calculated values with their measured values, their relative
      errors were less than 0.25. In spite of the large uncertainties in the model
      which is influenced by so many factors, the considerable validation of the model
      can be shown. Based on the discussion of distribution of the errors as well as
      the reasons causing the errors, a trial modification of the model was made. A
      modification function looked necessary when soil water content was <10%.

PMID- 15266077
TI  - Dosimetric assessment from 212Pb inhalation at a thorium purification plant.
AB  - At the Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, Brazil,
      there is a facility (thorium purification plant) where materials with high
      thorium concentrations are manipulated. In order to estimate afterwards the lung
      cancer risk for the workers, the thoron daughter (212Pb) levels were assessed and
      the committed effective and lung committed equivalent doses for workers in place.
      A total of 28 air filter samples were measured by total alpha counting through
      the modified Kusnetz method, to determine the 212Pb concentraion. The committed
      effective dose and lung committed equivalent dose due to 212Pb inhalation were
      derived from compartmental analysis following the ICRP 66 lung compartmental
      model, and ICRP 67 lead metabolic model.

PMID- 15266078
TI  - Theory of radon exhalation into accumulators placed at the soil-atmosphere
      interface.
AB  - A theoretical analysis is provided for the phenomenon of radon diffusion into
      cylindrical accumulators (inverted cups), which are commonly used for the
      measurement of radon exhalation rates from the earth's surface. Analytical
      solutions to the diffusion equations in the soil and the cup spaces are obtained
      by a two-dimensional (2-D) analysis that takes into account the perturbation in
      the horizontal and vertical radon concentration profiles brought about by the
      presence of the cup. The mixed nature of the boundary conditions at the soil
      surface and the cup-soil interface is handled by dual integral equation
      techniques. The treatment includes steady-state and time-dependent situations
      with and without ventilation. Formulae are derived for the effective time
      constant of radon build-up in the cup and for the back diffusion correction
      factors in different experimental situations. It is found that the effective time
      constant of radon build-up is much larger than the radon decay constant and it
      increases for smaller cups. The back diffusion correction factors to be employed
      in one-time measurement methods also increase as the cup dimensions decrease. The
      present work provides an analytical basis of an earlier numerical treatment for
      the growth curve analysis of the same problem. Although the results are based on
      the assumptions of somewhat ideal nature for mathematical tractability, they
      provide upper bound estimates of the phenomenon of back diffusion. Some practical
      applications of the results for extracting diffusion length of radon in materials
      are also suggested.

PMID- 15266079
TI  - Estimated potassium content in Hanford workers.
AB  - Potassium content in male and female workers at the US Department of Energy
      Hanford Site was estimated based on measurements made in 2002 of 40K activity in
      the body. The 40K activity in females ranged from 2.1 to 4.1 kBq with an average
      of 3.1 +/- 0.02 kBq. The total body potassium (TBK) content in females averaged
      98 +/- 0.6 g. The 40K activity in males ranged from 2.8 to 6.6 kBq with an
      average of 4.2 +/- 0.01 kBq and the average TBK was 136 +/- 0.3 g. The average
      TBK value for males aged 20-49 y was 140 g. The average TBK values for both
      genders decreased with age. The average potassium concentrations calculated for
      the different age ranges for males were 15-25% less than the value (1.9 gK per
      kg) obtained using the reported ICRP reference potassium and reference weight
      values. Potassium concentrations were inversely correlated with body-build index,
      body-mass index and body weight. These correlations could possibly be utilised to
      help assess the risk for disease. Future work is planned to evaluate whether
      monitoring of potassium concentrations could be used as a tool for the detection
      of diabetes and hypertension.

PMID- 15266080
TI  - Dose performance evaluation of a charge coupled device and a flat-panel digital
      fluoroscopy system recently installed in an interventional cardiology laboratory.
AB  - The purpose of the study was to evaluate the dose performance of a flat-panel
      (FP) and an image intensifier (II) charge coupled device (CCD) digital
      fluoroscopy X-ray systems newly installed in an Interventional Cardiology (IC)
      department. Filter entrance dose rate, detector dose rate (during fluoroscopy)
      and filter entrance dose per image were measured at 70 cm from the focus using 2
      mm copper sheets to mimic normal size patient. Image quality was also evaluated.
      The patient dose survey included 277 patients, which had either a Coronary
      Angiography (CA) or a Percutaneous Transluminal Coronary Angioplasty (PTCA). Dose
      area product (DAP), fluoroscopy time (T) and total number of frames (F) values
      were also collected. The results showed that both systems performed within
      international recommendations with the exception of higher cine radiation doses,
      stressing the fact that neither specific protocols of measurement nor reference
      values for digital equipment were provided by the official bodies.

PMID- 15266081
TI  - Adult reference levels in diagnostic and interventional radiology for temporary
      use in Switzerland.
AB  - This work aims at establishing a set of diagnostic reference levels (DRLs) for
      various types of examinations performed in diagnostic and interventional
      radiology. The average doses for 257 types of radiological examinations were
      established during the 1998 nationwide survey on the exposure of the Swiss
      population by radiodiagnostics. They were calculated using appropriate dosimetric
      models and average technical parameters. The DRLs were derived from the average
      doses using a multiplying factor of 1.5. The DRLs obtained were rounded and
      compared to the data reported in the literature. The results are in most cases
      comparable to the DRLs determined by the 3rd-quartile method. These discrepancies
      registered in some cases, particularly for complex examinations, can be explained
      by significant differences in the protocols and/or the technical parameters used.
      A set of DRLs is proposed for a large number of examinations to be used in
      Switzerland as temporary values until a national dosimetric database is set up.

PMID- 15266082
TI  - Generalised photon skyshine calculations.
AB  - The energy-dependent dose contributions from monoenergetic photon source points
      located 1.5 m above the ground have been tabulated. These values are intended to
      be used for regulatory compliance with site boundary dose limitations and as such
      are all presented in effective dose units. Standard air and soil are modelled
      where the air has vertical density gradient approximation. Energies from 0.05 up
      to 10 MeV are evaluated for dose transport up to 40 mean free paths.

PMID- 15266084
TI  - Are HPS N13.11-2001 test conditions and performance criteria appropriate for
      evaluating personal dosimetry systems?

PMID- 15266083
TI  - Dose area product reference levels in dental panoramic radiology.
AB  - The purpose of this study was to measure DAP (Dose Area Product) values in
      panoramic radiology with the use of a DAP meter, to determine corresponding
      reference levels, and to compare DAP between panoramic and intraoral radiology.
      DAP was measured in 62 panoramic X-ray units for 3 types of exposure (male,
      female and child) and in 20 intraoral X-ray units of 50, 60 and 70 kVp. DAP
      reference levels were 117 mGy cm2, 97 mGy cm2 and 77 mGy cm2 for exposure of a
      male, female and child respectively. Results showed that DAP from a panoramic
      dental examination is approximately twice that from a single intraoral
      examination. DAP meter is a very convenient and easy to use tool for patient
      dosimetry and for the establishment of reference levels in dental panoramic
      radiology.

PMID- 15266085
TI  - Kalman filtration of radiation monitoring data from atmospheric dispersion of
      radioactive materials.
AB  - A Kalman filter method using off-site radiation monitoring data is proposed as a
      tool for on-line estimation of the source term for short-range atmospheric
      dispersion of radioactive materials. The method is based on the Gaussian plume
      model, in which the plume parameters including the source term exhibit a 'random
      walk' process. The embedded parameters of the Kalman filter are determined
      through maximum-likelihood estimation making the filter essentially free of
      external parameters. The method is tested using both real and simulated radiation
      monitoring data. For simulated data, the method is shown to retrieve the embedded
      parameters employed in generating the data and to reconstruct the plume model
      parameters, including the source term. When tested against experimental radiation
      monitoring data the method is found accurately to uncover the known source term.

PMID- 15266086
TI  - Radiation dose to premature infants in neonatal intensive care units in Kuwait.
AB  - Entrance surface dose (ESD) and effective dose (E) to premature infants were
      estimated at three neonatal intensive care units in Kuwait for three standard X
      ray examinations--abdominal, chest and skull X rays using a simple water phantom.
      The ESD was found to vary between 58 and 102 microGy for abdominal X rays,
      between 51 and 102 microGy for chest X rays and between 58 and 145 microGy for
      skull examinations. These doses are comparable to the entrance skin doses
      published elsewhere. The E-values were estimated using normalised organ dose
      dataset from the National Radiological Protection Board. The E-values for
      abdominal, chest and skull examinations were in the ranges of 30-46, 20-36 and 8
      18 microSv per examination, respectively. The risk of developing childhood
      cancers from each of the three examinations was estimated to be in the range (9
      117) x 10(-6) for infants undergoing 25 of these X-ray examinations during their
      stay in the NIC unit.

PMID- 15266087
TI  - An algorithm to evaluate solar irradiance and effective dose rates using spectral
      UV irradiance at four selected wavelengths.
AB  - The paper shows a semi-analytical method for environmental and dosimetric
      applications to evaluate, in clear sky conditions, the solar irradiance and the
      effective dose rates for some action spectra using only four spectral irradiance
      values at selected wavelengths in the UV-B and UV-A regions (305, 320, 340 and
      380 nm). The method, named WL4UV, is based on the reconstruction of an
      approximated spectral irradiance that can be integrated, to obtain the solar
      irradiance, or convoluted with an action spectrum to obtain an effective dose
      rate. The parameters required in the algorithm are deduced from archived solar
      spectral irradiance data. This database contains measurements carried out by some
      Brewer spectrophotometers located in various geographical positions, at similar
      altitudes, with very different environmental characteristics: Rome (Italy), Ny
      Alesund (Svalbard Islands, Norway) and Ushuaia (Tierra del Fuego, Argentina). To
      evaluate the precision of the method, a double test was performed with data not
      used in developing the model. Archived Brewer measurement data, in clear sky
      conditions, from Rome and from the National Science Foundation UV data set in San
      Diego (CA, USA) and Ushuaia, where SUV 100 spectroradiometers operate, were drawn
      randomly. The comparison of measured and computed irradiance has a relative
      deviation of about +/-2%. The effective dose rates for action spectra of
      Erythema, DNA and non-Melanoma skin cancer have a relative deviation of less than
      approximately 20% for solar zenith angles <50 degrees .

PMID- 15266088
TI  - Effective dose to patient during cardiac interventional procedures (Prague
      workplaces).
AB  - The aim of this study was to assess effective dose to a patient during cardiac
      procedures, such as coronary angiography (CA) and percutaneous transiluminal
      angioplasty (PTCA). Measurements were performed on 185 patients in four
      catheterisation laboratories in three hospitals in Prague using the dose area
      product (DAP) meter. Calculations of surface and effective dose were performed
      with Monte-Carlo-based program PCXMC. The mean DAP value per procedure determined
      in all workplaces ranged between 25.0 and 54.5 Gy cm2 for CA and 43.0-104.5 Gy
      cm2 for PTCA. In three cases, the surface dose exceeded the 2 Gy level for
      occurrence of transient erythema. The mean effective dose per procedure in all
      workplaces was determined to be in the range of 2.7-8.8 mSv for CA and 5.7-15.3
      mSv for CA + PTCA combined. The results presented are comparable with those
      published by other authors.

PMID- 15266089
TI  - Molecularly targeted therapy: have the floodgates opened?

PMID- 15266090
TI  - Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and
      therapeutic applications.
AB  - Carcinogenesis is a multistep process characterized by genetic alterations that
      influence key cellular pathways involved in growth and development. Oncogenes
      refer to those genes whose alterations cause gain-of-function effects, while
      tumor suppressor genes cause loss-of-function effects that contribute to the
      malignant phenotype. The effects of these alterations are complex due to the high
      number of changes in a typical case of breast cancer and the interactions of the
      biological pathways involved. This review focuses on the more common
      abnormalities in oncogenes and tumor suppressor genes in human breast cancer and
      their known associations with clinical outcome in terms of tumor classification,
      prognosis, and response to specific therapies. A better understanding of these
      relationships has led to new therapeutic applications. Agents that target
      oncogenes and their associated pathways are now in clinical use, with many more
      undergoing preclinical and clinical testing. The availability of antibodies,
      small synthetic molecules, cyotokines, gene therapy techniques, and even natural
      compounds that are screened for specific biological properties has greatly
      increased the number of candidate drugs. Nevertheless, clinical successes have
      been limited because of the redundancy of many cancer-related pathways as well as
      the high degree of variability in genotype and phenotype among individual tumors.
      Likewise, strategies to replace tumor suppressor gene functions face numerous
      technical hurdles. This review summarizes the current achievements and future
      prospects for the therapeutic targeting of oncogenes and tumor suppressor genes
      and new technology to better classify tumors and accurately predict responses to
      standard and novel agents.

PMID- 15266091
TI  - Tamoxifen--what next?
AB  - Most patients with advanced breast cancer (ABC) ultimately die due to disease
      progression. Consequently, treatments for ABC are predominantly palliative in
      nature and, therefore, the tolerability profile of a given treatment is
      particularly relevant in these patients. While cytotoxic chemotherapy and
      endocrine therapy exhibit efficacy in hormone-sensitive, advanced disease, it is
      endocrine therapy that combines efficacy with minimal acute toxicity. Tamoxifen
      has been the chosen endocrine therapy for postmenopausal, hormone-sensitive, ABC
      for over 20 years. More recently, new endocrine agents with different mechanisms
      of action from tamoxifen have been introduced. Evidence indicates that the
      aromatase inhibitors anastrozole (Arimidex; AstraZeneca; Wilmington, DE),
      letrozole (Femara; Novartis Pharmaceuticals Corp.; East Hanover, NJ) and
      exemestane (Aromasin; Pharmacia Corp.; Peapack, NJ) offer superior efficacy and
      tolerability to tamoxifen in the first-line treatment of postmenopausal, hormone
      sensitive ABC. Similarly, after tamoxifen failure, fulvestrant (Faslodex;
      AstraZeneca), a new estrogen receptor (ER) antagonist that downregulates the ER,
      is at least as effective as anastrozole, is well tolerated, and is not cross
      resistant with tamoxifen. Unlike tamoxifen, fulvestrant has no known agonist
      effects. The sequential use of such agents may prolong the time during which
      endocrine therapies can be used, thereby avoiding the more acute toxicities
      associated with cytotoxic chemotherapy. Indeed, a series of studies has shown
      that this sequential use is a relevant, active, and well-tolerated option.
      Establishing the comparative efficacies and optimal sequences that incorporate
      the newer endocrine agents will be central in determining the future role of
      hormonal therapy in ABC; the results of this work will determine the relative
      place of tamoxifen in what is a rapidly changing therapeutic environment.

PMID- 15266092
TI  - Imaging the liver.
AB  - Imaging of the liver is undertaken for the detection and characterization of
      suspected primary or secondary neoplasms, prior to planning a surgery or
      chemotherapy pump placement, for assessing treatment response, for evaluating
      biliary pathology, and for screening for liver neoplasms in high-risk groups. In
      this article, we review the advantages and disadvantages of various imaging
      modalities in the evaluation of the liver and formulate guidelines for the
      imaging of common clinical indications. A brief review of imaging findings in
      focal and diffuse liver disease is also presented.

PMID- 15266093
TI  - Dilemmas in management: the controversial role of chemotherapy in PS 2 advanced
      NSCLC and the potential role of CT-2103 (Xyotax).
AB  - Platinum-based chemotherapy improves long-term survival in patients with advanced
      non-small cell lung cancer (NSCLC). Meta-analyses have demonstrated an
      improvement in median and 1-year survival times as well as quality of life.
      However, these benefits are largely confined to patients with a good performance
      status (PS), one of the most critical determinants influencing outcome. Several
      clinical trials that initially included PS 2 patients ultimately discontinued
      their enrollment due to a high propensity of adverse reactions to treatment. The
      advent of more active, less toxic agents has revitalized investigator interest in
      treating PS 2 patients. CT-2103 is a novel paclitaxel conjugate undergoing
      investigation in the treatment of advanced NSCLC. The median survival for PS 2
      patients treated with single-agent CT-2103 in one small trial proved similar to
      that reported for paclitaxel/carboplatin in NSCLC patients and was associated
      with an improved safety profile compared with conventional taxanes. Phase III
      studies comparing CT-2103 as a single agent and in combination with carboplatin
      to current standards of care are in progress. Unlike a well-defined population
      with good PS, the therapeutic index in PS 2 patients is narrower and not as
      clearly defined. These and other efforts will determine the optimal mode of
      therapy in PS 2 individuals with NSCLC.

PMID- 15266094
TI  - Clinical mimics of lymphoma.
AB  - Lymphadenopathy is a common clinical finding and is frequently benign. Warning
      signs suggestive of a malignant etiology include lymph nodes >2 cm in size,
      supraclavicular location, and generalized lymphadenopathy associated with
      hepatosplenomegaly or systemic symptoms. A metastatic solid tumor is always in
      the differential diagnosis of localized lymphadenopathy, particularly in older
      individuals. In the case of more generalized lymphadenopathy, in addition to the
      more common lymphomas, benign etiologies as well as benign and atypical
      lymphoproliferative disorders need to be considered. Benign etiologies of
      lymphadenopathy can include infections, autoimmune disorders, drug
      hypersensitivity reactions, sarcoidosis, and amyloidosis. Rare but benign
      lymphoproliferative disorders include Kikuchi's disease, Rosai-Dorfman disease,
      and progressive transformation of germinal centers. Atypical lymphoproliferative
      disorders that bear close surveillance for evolution to a more aggressive
      malignancy include Castleman's disease, lymphomatoid granulomatosis, and
      lymphomatoid papulosis. Previously considered in this category but now classified
      as a true lymphoma is angioimmunoblastic lymphadenopathy with dysproteinemia.
      Physicians need to be aware of all of these disorders when evaluating suspicious
      lymphadenopathy, while also considering the more common lymphomas and leukemias.

PMID- 15266095
TI  - Serum CA125: a tumor marker for monitoring response to treatment and follow-up in
      patients with non-Hodgkin's lymphoma.
AB  - PURPOSE: Serum CA125 is an important prognostic factor in patients with non
      Hodgkin's lymphoma (NHL). Elevation of CA125 level correlates with advanced
      disease, poor response to treatment, and poor survival rates. The aim of the
      current study is to evaluate CA125 levels in patients with NHL and to investigate
      the correlations between high CA125 level and other presenting features.
      MATERIALS AND METHODS: Thirty-eight patients (14 with low-grade and 24 with
      aggressive histologically proven NHL) were studied prospectively. Serum CA125
      assessment was done at diagnosis, during treatment, and at follow-up. The
      associations between CA125 levels and other presenting features were examined.
      RESULTS: CA125 levels were elevated in 43% of patients with low-grade NHL and in
      46% of patients with aggressive NHL (i.e., 45% of all patients). A higher CA125
      level was associated with advanced disease, bone marrow involvement, extranodal
      involvement, poor performance status, the presence of B symptoms, and high serum
      lactate dehydrogenase level. Complete responses occurred in 86% of patients with
      normal CA125 levels and in 59% of patients with elevated CA125 levels. In both
      low-grade and aggressive NHL, the estimated 5-year overall survival rate was
      higher in patients with normal CA125 levels than in patients with elevated CA125
      levels (88% versus 50% and 70% versus 27%, respectively). CONCLUSION: High serum
      CA125 is an important prognostic factor in NHL and correlates with more advanced
      disease, low response rates, and worse survival. CA125 measurements may be used
      for staging, monitoring response to treatment, and follow-up of patients with
      NHL.

PMID- 15266096
TI  - Biology and therapeutic advances for pediatric osteosarcoma.
AB  - Osteosarcoma is the most common malignant bone tumor in children and adolescents.
      Survival for these patients was poor with the use of surgery and/or radiotherapy.
      The introduction of multi-agent chemotherapy dramatically improved the outcome
      for these patients and the majority of modern series report 3-year disease-free
      survival of 60%-70%. This paper describes current strategies for treating
      patients with osteosarcoma as well as review of the clinical features, radiologic
      and diagnostic work-up, and pathology. The authors review the state of the art
      management for patients with osteosarcoma in North America and Europe including
      the use of limb-salvage procedures and reconstruction as well as discuss the
      etiologic and biologic factors associated with tumor development. Therapy-related
      sequelae and future directions in the biology and therapy for these patients are
      also discussed.

PMID- 15266097
TI  - Conformal radiation therapy for childhood CNS tumors.
AB  - Radiation therapy plays a central role in the management of many childhood brain
      tumors. By combining advances in brain tumor imaging with technology to plan and
      deliver radiation therapy, pediatric brain tumors can be treated with conformal
      radiation therapy. Through conformal radiation therapy, the radiation dose is
      targeted to the tumor, which can minimize the dose to normal brain structures.
      Therefore, by limiting the radiation dose to normal brain tissues, conformal
      radiation therapy offers the possibility of limiting the long-term side effects
      of brain irradiation.In this review, we describe different approaches to
      conformal radiation therapy for pediatric central nervous system tumors
      including: A) three-dimensional conformal radiation therapy; B) stereotactic
      radiation therapy with arc photons; C) intensity-modulated radiation therapy; and
      D) proton beam radiation therapy. We discuss the merits and limitations of these
      techniques and describe clinical scenarios in which conformal radiation therapy
      offers advantages over conventional radiation therapy for treating pediatric
      brain tumors.

PMID- 15266098
TI  - Effectiveness of darbepoetin alfa versus epoetin alfa in patients with
      chemotherapy-induced anemia treated in clinical practice.
AB  - PRIMARY PURPOSE: The objective of this retrospective observational cohort study
      was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in
      patients with chemotherapy-induced anemia using data from noncontemporaneous
      chart audits conducted at a community-based oncology practice. MATERIALS AND
      METHODS: For the first chart audit, data were collected from consecutive patients
      with nonmyeloid malignancies with diagnoses of chemotherapy-induced anemia and
      hemoglobin levels < or = 10.5 g/dl who were receiving concurrent chemotherapy and
      had at least 5 weeks of visits from July-September 2000. After therapeutic
      substitution of darbepoetin alfa for epoetin alfa for all patients with
      chemotherapy-induced anemia, data were collected from consecutive darbepoetin
      alfa-treated patients with diagnoses of chemotherapy-induced anemia and at least
      8 weeks of visits from June-October 2002 (darbepoetin alfa was approved in July
      2002). RESULTS: Most (86%) of the 212 epoetin alfa-treated patients had received
      an initial dose of 40,000 U once weekly, and most (85%) of the 196 darbepoetin
      alfa-treated patients had received a fixed dose of either 100 microg once weekly
      (49%) or 200 microg every 2 weeks (36%). At 8 weeks, the mean change in
      hemoglobin level was 1.1 g/dl for the darbepoetin alfa patient group and 1.0 g/dl
      for the epoetin alfa patient group. DISCUSSION: Utilization, dose escalation
      rates, and clinical outcomes were considered comparable for the darbepoetin alfa
      and epoetin alfa patient groups. CONCLUSIONS: Darbepoetin alfa, 100 microg once
      weekly or 200 microg every 2 weeks, appears to be as effective as epoetin alfa,
      40,000 U once weekly, for the treatment of chemotherapy-induced anemia in the
      clinical practice setting.

PMID- 15266099
TI  - Effectiveness and safety of an induction therapy with epoetin alfa in anemic
      cancer patients receiving concomitant chemotherapy.
AB  - BACKGROUND: Epoetin alfa, administered at standard dosages of 10,000-20,000 IU
      three times weekly or 40,000-60,000 IU once weekly, has been shown to
      significantly increase hemoglobin (Hb) levels, decrease transfusion requirements,
      and improve quality-of-life parameters in patients undergoing
      chemotherapy.Objective. This open-label, nonrandomized, historically controlled
      study was conducted to evaluate the efficacy and safety of an induction dose of
      epoetin alfa in patients with moderate or severe anemia who were receiving
      chemotherapy. METHODS: Nineteen patients with solid tumors and Hb levels < 9.0
      g/dl were enrolled. The patients received single s.c. injections of epoetin alfa,
      40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the
      following 30 days. Nineteen other cancer patients who had matching
      characteristics and had received epoetin alfa, 10,000 IU, three times weekly for
      the 45-day study period, served as historical controls. The primary efficacy
      variable was change in Hb level from baseline to days 15 (approximately week 2)
      and 45 (approximately week 6.5). Secondary efficacy variables included the
      percent response (Hb increase > or = 1 g/dl) and percent major response (Hb
      increase > or = 2 g/dl) at days 15 and 45, the durations of response and major
      response after day 45, the proportion of patients transfused within the 45 study
      days, the changes in Eastern Cooperative Oncology Group performance status score
      at days 15 and 45, and the ability to maintain the planned chemotherapy dose
      (dose intensity) over the 45-day study. RESULTS: Mean increases in Hb level in
      the epoetin alfa 40,000 IU group were significantly greater than those in the
      historical control group both at day 15 and at day 45. The increase in Hb level
      in the control group approximated increases reported with standard 3-times-weekly
      epoetin alfa at day 15 but was somewhat lower than the increases typically seen
      by day 45, presumably due to the fact that, in the present study, the epoetin
      alfa dose was not doubled in initial nonresponders, as is commonly done with
      standard epoetin alfa treatment. The rates of major response for epoetin alfa
      40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for
      control patients (16% and 21%, respectively). Also, the transfusion rate was
      lower and performance status scores were better in the epoetin alfa 40,000 IU
      patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU
      patients versus 47% of control patients received 100% of the planned chemotherapy
      dose. Epoetin alfa was well tolerated in both treatment groups. CONCLUSIONS:
      Results of this study suggest that epoetin alfa at a dose of 40,000 IU
      administered five times over 2 weeks may confer even higher response rates than
      those seen with standard dosing regimens. These encouraging results support
      further study of the proposed induction dose of epoetin alfa in a larger,
      randomized, prospectively controlled trial.

PMID- 15266100
TI  - The molecular perspective: polycyclic aromatic hydrocarbons.

PMID- 15266101
TI  - Breast cancer highlights: key findings from the San Antonio Breast Cancer
      Symposium: a U.S. perspective.
AB  - The San Antonio Breast Cancer Symposium has become one of the leading forums for
      communication of important discoveries in breast cancer research. Over the past
      couple of years, seminal, practice-changing results have been presented at this
      meeting. The aromatase inhibitors represent the most effective endocrine
      interventions for postmenopausal women with hormone receptor-positive breast
      cancer. Their introduction into the adjuvant therapy of primary breast cancer was
      prompted by evidence from the ATAC trial. Progress in adjuvant chemotherapy
      included the introduction to taxanes, and more recently, the demonstration that
      the dose-dense administration of paclitaxel in association with doxorubicin and
      cyclophosphamide resulted in significant improvements in relapse-free and overall
      survival rates. Molecular targets have become accepted as rational targets, and
      targeted therapies are proceeding through clinical trials. The success of
      trastuzumab elicited much excitement, but a number of theoretical and practical
      hurdles must be overcome before other molecularly targeted agents are
      incorporated into standard therapy of primary and metastatic breast cancer.

PMID- 15266102
TI  - Interwoven ubiquitination oscillators and control of cell cycle transitions.
AB  - Ubiquitin-mediated proteolysis has emerged as a paramount mechanism for
      regulating the cell division cycle. Changes in the activities of certain E3
      ligases can promote the interconversion of cell cycle states or transitions.
      Recent studies have revealed how distinct E3 ligases control the activity of
      other E3 ligases and how the interplay between these degradation machines sets up
      the timing of cell cycle transitions. For example, during G1, the anaphase
      promoting complex in conjunction with Cdh1 (APC(Cdh1)) catalyzes destruction of
      the S-phase activator Skp2, helping to define the G1 state. In response to poorly
      defined signals, APC(Cdh1) activity is reduced, allowing accumulation of Skp2 and
      therefore entry into S phase. In many cases, E3 ligases also function to
      ubiquitinate proteins that negatively regulate cell cycle transitions. Recent
      work indicates that cyclin-dependent kinase 2 and Polo kinase collaborate to
      phosphorylate Wee1, thereby promoting its ubiquitination by SCF(beta-TRCP). Thus,
      activation of the mitotic transition produces feedback signals that help to turn
      off the negative upstream pathway to further reenforce the transition.

PMID- 15266103
TI  - 14-3-3 proteins: a number of functions for a numbered protein.
AB  - Many signal transduction events are orchestrated by specific interactions of
      proteins mediated through discrete phosphopeptide-binding motifs. Although
      several phosphospecific-binding domains are now known, 14-3-3s were the first
      proteins recognized to specifically bind a discrete phosphoserine or
      phosphothreonine motif. The 14-3-3 proteins are a family of ubiquitously
      expressed, exclusively eukaryotic proteins with an astonishingly large number of
      binding partners. Consequently, 14-3-3s modulate an enormous and diverse group of
      cellular processes. The effects of 14-3-3 proteins on their targets can be
      broadly defined using three categories: (i) conformational change; (ii) physical
      occlusion of sequence-specific or structural protein features; and (iii)
      scaffolding. This review will describe the current state of knowledge on 14-3-3
      proteins, highlighting several important advances, and will attempt to provide a
      framework by which 14-3-3 functions can be understood.

PMID- 15266104
TI  - Characterization of bro-a gene of Spodoptera litura multicapsid
      nucleopolyhedrovirus.
AB  - Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) ORF120 (designated
      as the bro-a gene) is a member of the unique multigene family called the
      baculovirus repeated ORFs (bro) family. Computer-assisted analysis revealed that
      BRO-A does not contain the conserved Bro-N domain in its N-terminus, but contains
      a single-stranded DNA binding motif near its C-terminus. Transcriptional analysis
      indicated that bro-a transcript initiated within a baculovirus consensus early
      start site motif (ATCAGT). In vitro the bro-a gene transcript was present at 12 h
      post infection (p.i.) and remained detectable up to 96 h p.i. Western blot
      analysis of BRO-A expression in SpltMNPV infected S. litura cells showed that it
      was present from 72 h to 96 h p.i. in vitro. Analysis of extracts from nuclear
      structures indicated that BRO-A could not be extracted with DNA or proteins which
      bind to DNA.

PMID- 15266105
TI  - Complete nucleotide sequence of a strawberry isolate of Beet pseudoyellows virus.
AB  - In our effort to identify the causal agent(s) of strawberry pallidosis we found a
      single pallidosis positive plant that did not give any amplicons after RT-PCR
      using primer sets representing multiple regions of Strawberry pallidosis
      associated virus (SPaV) genome and failed to react with antibodies directed
      against the recombinant coat protein (CP) of SPaV. DsRNA extracted from this
      plant showed a similar pattern to that of SPaV indicating that another crinivirus
      may infect strawberry. Sequence analysis of multiple cDNA clones corresponding to
      the heat shock 70 homolog gene (HSP70h) of the unknown virus indicated that it
      was Beet pseudoyellows virus (BPYV). Analysis of the complete nucleo- tide
      sequence of BPYV-strawberry revealed that this isolate has several distinct
      features when compared to Cucumber yellows virus (CuYV), a cucumber strain of
      BPYV, including an entire ORF not found in CuYV.

PMID- 15266106
TI  - Regulation of the vhs gene promoter of pseudorabies virus by IE180 and EP0, and
      the requirement of a Sp1 Site for the promoter function.
AB  - The virion host shutoff (vhs) protein is a virion component of
      Alphaherpesviruses, including pseudorabies virus. In this work, the upstream
      sequences of vhs gene of pseudorabies virus (TNL strain) was cloned and
      sequenced. We linked the upstream sequences of vhs gene to the CAT reporter gene
      and examined the promoter function of this region. The immediate-early protein
      IE180 of Pseudorabies Virus (PRV) is expressed immediately after infection and
      plays a vital role in the regulation of other viral genes. Our results
      demonstrated that the vhs promoter was regulated by the IE180 in a dosage
      dependent manner; the vhs promoter was stimulated by low concentration of IE180
      but suppressed by high concentration of IE180. Mutational analysis indicated that
      the only IE180 binding site at the vhs promoter was not essential for its
      function; however, a Sp1 binding site (15 bp downstream to TATA box) was critical
      to its function. In addition, the result of cotransfection demonstrated that
      early protein 0 (EP0) of PRV, another protein with transcriptional function,
      inhibited the activity of the vhs promoter.

PMID- 15266107
TI  - Evidence for Selection of more Adapted Human Immunodeficiency Virus Type 1
      Recombinant Strains in a Dually Infected Transfusion Recipient.
AB  - Human immunodeficiency virus type-1 (HIV-1) genetic diversity is one of the
      remarkable characteristics of these viruses, and the mechanisms involved in the
      selective forces driving HIV-1 evolution are of great interest. Samples from
      hosts infected with multiple distinct strains represent a valuable in vivo
      resource to investigate the role of recombination in the natural evolution of HIV
      1. This work describes a detailed study regarding the evolution of the envelope
      gene (env) (C2-V5 region) in a dually infected child who received blood
      transfusions simultaneously from two distinct HIV-1 infected donors. In this
      study, we were able to directly compare the data obtained from the dually
      infected recipient with data obtained from two other singly HIV-1 infected
      children who had received blood transfusion from each of the two donors.
      Sequences from the singly infected children clustered into two distinct groups,
      each related to the respective donor-derived sequence by phylogenetic analysis,
      and hence were consistent with the epidemiological data. In the case of the
      dually infected child, a high degree of recombination between the two donor
      derived sequences was observed at the C2-V3 region, whereas in the V4-V5 region
      selection of only one derived donor sequence was seen. Measurement of
      nonsynonymous versus synonymous substitution rates at each region revealed that
      negative selection was the main evolutionary force acting on the viral population
      of the dually infected child, regardless of the genetic mechanism by which each
      region evolved. Based on direct comparison with data obtained for the two singly
      infected children we propose that the higher amount of viral diversity observed
      in HIV-1 multi-infection events, as in the case of the dually infected patient,
      might contribute to maximizing selective advantage and possibly minimizing immune
      response. We conclude that recombination shaped by selective forces may increase
      the adaptive potential of HIV-1.

PMID- 15266108
TI  - Neuronal localization of simian varicella virus DNA in ganglia of naturally
      infected African green monkeys.
AB  - In situ hybridization analysis of monkey ganglia 2 months after natural infection
      with simian varicella virus (SVV) revealed SVV DNA only in neurons. These
      findings parallel the detection of varicella zoster virus in neurons of latently
      infected human ganglia. Natural exposure to SVV provides a model system to study
      varicella latency.

PMID- 15266109
TI  - Stable and unstable mutations in the 5' non-translated regions of tomato aspermy
      virus RNAs 1 and 2 generated de novo from infectious cDNA clones containing a
      cauliflower mosaic virus 35S promoter.
AB  - Tomato aspermy virus RNAs derived from infectious cDNA clones exhibited a number
      of sequence alterations in the 5' non-translated region (NTR). These included a
      deletion of the first four residues in both RNAs 1 and 2, transversion of residue
      5 from a G to a U in RNA 1, and transversion of A to C at position of 50 of RNA
      1. These alterations were not stable in the infected plants while the insertion
      of a U residue between nucleotides 1 and 5 of RNA 1 was stable in the infected
      plants. Generation of these sequence alternations was not dependent upon either
      the host species or the concentration of the inoculum. The sequence alterations
      also did not occur on passage of wildtype virus. Rather, the sequence alterations
      related to transcription from the cauliflower mosaic virus 35S RNA promoter
      driving infectious cDNAs. The alternations observed had no impact on symptoms or
      infectivity, but did affect the accumulation of specific viral RNAs. The data
      also demonstrated the existence of some plasticity in the sequence of the 5' NTR.

PMID- 15266110
TI  - Sequence analysis of the variable VP2 gene of infectious bursal disease viruses
      passaged in Vero cells.
AB  - Korean field infectious bursal disease viruses (IBDVs) were isolated from IBDV
      suspected commercial chickens. A previous study revealed that these IBDV field
      isolates were virulent or very virulent IBDVs. The isolates were passaged three
      times in the chorioallantoic membrane of specific-pathogen-free embryonated
      chicken eggs and four times in Vero cells. After passage, viral RNAs were
      isolated and purified to determine the genetic changes. The hypervariable regions
      of the VP2 gene were amplified by reverse transcriptase-polymerase chain reaction
      (RT-PCR). To confirm the genetic changes, PCR products were cloned, sequenced and
      compared to the sequences of the parental IBDVs and published IBDV strains. By
      sequencing analysis, the passaged IBDVs had amino acid changes at positions 253
      (Q --> H), 279 (D or N --> N) and 284 (A --> T) which were commonly found in the
      attenuated IBDV strains. Two serines in the serine-rich heptapeptide (residue 326
      332) were substituted into other amino acids which were similar to the IBDV
      vaccine strains.

PMID- 15266111
TI  - Peculiarities of herpes simplex virus (HSV) transcription: an overview.
AB  - The herpes simplex virus (HSV) has a 152 kbp dsDNA encoding probably 84 proteins.
      The approximate number of ORFs is 94, from which seven are doubled. The most
      probable number of single copy ORFs is 84 after omitting the two latency
      associated transcripts (LAT)/ORFs and the putative UL27.5 ORF. The high gene
      number creates a "crowded" genome with several overlapping transcripts. The
      unique long (U(L)) segment has at least 10 interposed ORFs, the existence of
      which was not obvious at first sequence analysis, while the unique short (U(S))
      segment has two such genes. The surplus of ORFs causes complex transcription
      patterns: (1) Transcripts with common initiation signals but different
      termination; (2) Transcripts with different initiation sites but co-terminal
      ends; (3) "Nested" transcripts differing at both, the initiation as well as
      termination signals, having partially collinear sequences. At least three or
      possibly four ORF (gene) pairs (UL9.5/UL10; UL27/UL27.5; UL43/UL43.5; ICP34.5/ORF
      P and O) occupy both DNA strands at complementary positions rising anti-sense
      transcripts expressed by an antagonistic mechanism of mutual exclusion. The anti
      sense mRNA mechanism might also operate when either LAT or ICP0 ORFs are
      expressed during latency assuring the absence of lytic virus replication. In
      contrast, during productive replication the cascade regulation of gene expression
      predominates, based on stepwise activation of immediate early (IE), early (E),
      early late (EL) and late (L) promoters. The promoters of different expression
      kinetic classes (alpha, beta, gamma-1 and gamma-2) are equipped with different
      number of cellular transcription factor binding and/or enhancer motifs.
      Surprisingly, only a few HSV mRNAs are being spliced (ICP0, UL15, US1,
      US12/ICP47). As reviewed here, the transcription pattern of the great majority of
      overlapping ORFs within the HSV-1 was quite convincingly elucidated, with
      exception of the putative UL27.5 gene. The UL27.5 transcript was not identified
      yet. Since the existence of the UL27.5 gene was based on indirect rather than
      direct evidence, it needs final confirmation.

PMID- 15266112
TI  - Detection of human immunodeficiency virus type 1 envelope peptide- stimulated T
      helper cell responses and variations in the corresponding regions of viral
      isolates among vertically infected children.
AB  - Although human immunodeficiency virus type 1 (HIV-1) specific CD4 T-helper cells
      are vital in mediating antiviral defence, little is known concerning the
      influence of HIV-1 antigenic variation on CD4 T-cell responses. In this study,
      the amino acid sequences of 5 synthetic HIV-1 envelope peptides used for in vitro
      stimulation (T2, P18 MN, P18 IIIB, T1 and TH4.1) were compared to the
      corresponding amino acid sequences of the gp 160 region of viruses isolated from
      HIV-1 infected children to determine whether variation in the envelope region of
      HIV-1 was associated with the ability to detect Env-specific T-helper cell
      responses. Although the T2 region appeared to offer some evidence as to the role
      antigenic variation may have played in class II-restricted CD4 T-cell responses
      between those children who showed a detectable Env-stimulated T-helper cell
      response and those who did not, the other regions studied showed no evidence of
      being more conserved among those children who showed detectable responses. The
      combined amino acid variation across the specific peptide regions studied was not
      associated with peripheral levels of HIV-1, nor did the degree of amino acid
      variation dictate the clinical category into which the children had been
      classified, although there was a tendency towards HIV-1 isolates from the younger
      children showing a greater degree of amino acid variation than isolates from the
      older children. These results suggest that HIV-1 specific CD4 responses may be
      somewhat tolerant of viral variation, although further studies are required to
      fully elucidate the effect of antigenic variation on immune recognition.

PMID- 15266114
TI  - Construction of a novel shuttle vector based on an RCR-plasmid from a
      haloalkaliphilic archaeon and transformation into other haloarchaea.
AB  - The pNB101 is the first plasmid to be isolated from an haloalkaliphilic archaea.
      With insertion of the ColE1 replicon of Escherichia coli, as well as two
      antibiotic resistance genes at its unique Hin dIII site, a novel shuttle vector
      between haloarchaea and E. coli was developed. This vector, named pNB102, was
      successfully transformed into two non-alkaliphilic haloarchaea, Halobacterium
      salinarum SNOB and Haloarcula hispanica ATCC33960. The presence and stability of
      pNB102 in the transformants were confirmed by PCR identification, Southern
      blotting and restriction endonuclease digestion. Results also indicated that the
      presence of restriction-modification (R-M) systems in some Halobacterium species
      prevented this transformation. It is the first report that the replicon of pNB101
      has such a wide host range, and has taken the first step for construction of the
      vector/host system in haloalkaliphilic archaea.

PMID- 15266113
TI  - HIV-1 induced AIDS is an allergy and the allergen is the Shed gp120--a review,
      hypothesis, and implications.
AB  - The possibility that the induction of T helper 2 (Th2) cytokine synthesis and the
      gradual increase in interleukin 4 (IL-4) and IgE levels during HIV-1 infection
      are an allergic response to HIV-1 proteins was raised in the author's previous
      article [Becker, Virus Genes 28, 1-4, 2004]. The present review extends this
      hypothesis by citing experimental reports which indicate that HIV-1 shed gp120
      virions share a striking resemblance with the allergens that bind to IgE
      molecules bound to Fc epsilon receptor I-positive (Fc epsilon RI) cells (mast
      cells, basophils, monocytes, and dendritic cells, DC) and then induce them to
      release and synthesize the IL-4 cytokine. In the earlier review, it was
      established that the IL-4 cytokine is responsible for the following processes:
      IgE synthesis by B cells and the inhibition of antiviral IgG synthesis; the
      inactivation of T helper 1 (Th1) cells; and the inhibition of the antiviral
      cytotoxic T cell (CTL) response. The binding of the shed gp120 to B cell-bound
      immunoglobulin (Ig) depletes these cells. Moreover, it was reported that the
      viral regulatory proteins Tat and Vpr also stimulate IL-4 release from basophils.
      The mode of action used by HIV-1 gp120 in the induction of IL-4 [Becker, Virus
      Genes 28, 1-14, 2004] revealed that the viral protein contains a superantigen
      (SAg) domain that is capable of binding to the V(H)3 domain of IgE and Ig;
      namely, the shed gp120 protein act as endogenous and environmental allergens that
      bind to IgE molecules, which are bound to the Fc epsilon RI receptors on
      hematopoietic cells. Based on these findings, it is hypothesized that gp120 is an
      allergen. Consequently, it can be inferred that the active replication of HIV-1
      in infected individuals constantly exposes the immune system to an increase in
      the allergen content until the host immunity is eventually compromised. These
      finding suggest that HIV-1 engage in a two-pronged attack of the human immune
      system: it infects Th2 cells, macrophages, and DCs and then replicates at these
      venues; and the shed gp120 cells cause an allergy. This allergic condition
      consequently prevents the induction of Th1 cells, cytokine synthesis, and
      antiviral CTLs that are needed to clear the infecting virus and thus devitalizes
      the antivirals that are used to treat the virus infection. It was hypothesized
      [Becker, Virus Genus 28, 1-14, 2004] that the HIV-1 induced allergy can be
      treated with IL-4 inhibitors or immune response modifiers. A treatment that
      employs both antivirals and anti-allergen drugs may very well defeat the AIDS
      syndrome. Another implication of the present hypothesis is the need to improve
      the viral antigen used for vaccinating healthy individuals against HIV-1
      infection. It is thus suggested harmful domains be eliminated from the gp120.

PMID- 15266115
TI  - Construction and application of a promoter-trapping vector with methyl parathion
      hydrolase gene mpd as the reporter.
AB  - A facilitative and efficient promoter-trapping vector, pUC-mpd, was constructed
      with the promoterless methyl parathion hydrolase gene as the reporter. This
      reporter gene is easily used to clone promoters with different promoting strength
      on selective plates. Promoter regions of the ytkA and ywoF genes with strong
      promoting and signal peptide functions were cloned from the Bacillus subtilis 168
      genomic promoter library with this vector.

PMID- 15266116
TI  - Transformation of alternan-producing strains of Leuconostoc by electroporation.
AB  - Alternan-producing Leuconostoc mesenteroides strain NRRL B-1355 and its
      glucansucrase-negative derivative NRRL B-21414 were transformed by
      electroporation using four Gram positive-Gram negative shuttle vectors. Optimal
      conditions were 400 Omega and 10 kV cm(-1), resulting in transformation
      efficiencies of up to 3.5 x 10(4) per microg DNA. Relatively low copy numbers and
      native plasmids made it difficult to visualize the introduced plasmids on
      ethidium bromide-stained gels and, in some cases, on blot hybridizations.
      However, PCR analysis indicated that 95% of putative transformants carried
      plasmid sequences. Direct colony PCR was shown to work well for this system and
      also for transformants of L. mesenteroides subsp. cremoris.

PMID- 15266117
TI  - Anti-fungal effects of phenolic amides isolated from the root bark of Lycium
      chinense.
AB  - Four phenolic amides, dihydro-N-caffeoyltyramine (1), trans-N-feruloyloctopamine
      (2), trans-N -caffeoyltyramine (3), and cis-N-caffeoyltyramine (4), were isolated
      from an ethyl acetate extract of the root bark of Lycium chinense Miller. All had
      an anti-fungal effect; compounds 1-3 were potent at 5-10 microg ml(-1) and were
      without hemolytic activity against human erythrocyte cells. Compound 4 was active
      at 40 microg ml(-1). All four compounds impeded the dimorphic transition of
      pathogen, Candida albicans.

PMID- 15266118
TI  - Isolation and characterization of the CD133+ precursors from the ventricular zone
      of human fetal brain by magnetic affinity cell sorting.
AB  - A fast and effective method to enrich large number of neural precursors from the
      ventricular zone of human fetus by magnetic affinity cell sorting (MACS) is
      reported. After incubation with phycoerythrin (PE)-conjugated anti-CD133
      antibodies and anti-PE magnetic beads followed by one cycle of MACS, CD133(+)
      cells were harvested at 85% purity as confirmed by flow-cytometry and
      immunocytochemistry. In contrast to CD133(-) cells, these CD133(+) cells
      initiated primary and secondary neurospheres in culture, and the progeny of
      sorted cells could be differentiated into both neurons and glia, indicating that
      these highly enriched cells are capable of self-renewal and multi-lineage
      potential.

PMID- 15266119
TI  - Estimating the energetic contribution of hydrogen bonding to the stability of
      Candida methylica formate dehydrogenase by using double mutant cycle.
AB  - An homology model of Candida methylica formate dehydrogenase (cm FDH) was
      constructed based on the Pseudomonas sp. 101 formate dehydrogenase (ps FDH)
      structure. In wild type cm FDH, Thr169 and Thr226 can form hydrogen bonds with
      each other. We measured the interaction energy between the two threonines
      independent of other interactions in the proteins by using a so-called double
      mutant cycle and assessing the protein stability from the concentration of
      guanidine hydrochloride needed to denature 50% of the molecules. We conclude that
      the hydrogen bonds stabilize the wild type protein by -4 kcal mol(-1).

PMID- 15266120
TI  - Model-based optimization of biosurfactant production in fed-batch culture
      Azotobacter vinelandii.
AB  - Fed-batch cultivation of Azotobacter vinelandii 21was optimized for biosurfactant
      production. Optimization of feed-rate time profile and concentration of nutrient
      medium components in feeding solution is based on a hybrid mathematical model
      consisting of mass-balance equations for biomass, biosurfactant, volume of
      cultural liquid and substrate components: glucose, ammonia nitrogen and phosphate
      phosphorus. The rate of cultural liquid emulsification activity growth as well as
      the rates of ammonia nitrogen and phosphate phosphorus consumption is modelled by
      means of artificial neural network, while the rates of the other biochemical
      transformations are modelled by adequate kinetic relationships.

PMID- 15266121
TI  - Stable and specific expression of 4-coumarate:coenzyme A ligase gene (4CL1)
      driven by the xylem-specific Pto4CL1 promoter in the transgenic tobacco.
AB  - The ability of 4-coumarate:coenzyme A ligase promoter from Populus tomentosa
      (Pto4CL1p) to drive expression of the GUS reporter gene and 4-coumarate:coenzyme
      A ligase gene in tobacco has been studied using transgenic plants produced by
      Agrobacterium-mediated transformation. Intense GUS histochemical staining was
      detected in the xylem of stem in transgenic tobacco plants carrying the 1140 bp
      Pto4CL1p promoter. To further investigate the regulation function of the tissue
      specific expression promoter, Pto4CL1p, a binary vector containing Pto4CL1p
      promoter fused with 4CL1 gene was transferred into tobacco. The activity of the
      4CL1 enzyme doubled in the stems of transgenic tobacco but did not increase in
      the leaves. The content of lignin was increased 25% in the stem but there was no
      increase in the leaves of transgenic tobacco.

PMID- 15266122
TI  - Cloning and nucleotide sequence of a novel cry gene from Bacillus thuringiensis.
AB  - A cry1Ab-type gene was cloned from a new isolate of Bacillus thuringiensis by
      PCR. When restriction pattern was compared with that of known genes it was found
      to have additional restriction site for ClaI. Nucleotide sequencing and homology
      search revealed that the toxin shared 95% homology with the known Cry1Ab proteins
      as compared to more than 98% homology among the other reported Cry1Ab toxins. The
      gene encoded a sequence of 1,177 amino acids compared to 1,155 amino acids
      encoded by all the other 16 cry1Ab genes reported so far. An additional stretch
      of 22 amino acids after the amino acid G793 in the new toxin sequence showed 100%
      homology with several other cry genes within cry1 family. Homology search
      indicated that the new cry1Ab-type gene might have resulted by nucleotide
      rearrangement between cry1Ab and cry1Aa/cry1Ac genes.

PMID- 15266123
TI  - In vivo monitoring of intracellular expression of human interleukin-2 using green
      fluorescent protein fusion partner in Pichia pastoris.
AB  - The use of Pichia pastoris for protein production was simplified by creation of
      fusion proteins containing green fluorescent protein (GFP) and the product of
      interest. Human interleukin-2 (hIL-2) was used as a model product: GFP enabled
      clear identification of fusion protein expression and, more importantly, the
      quantification of hIL-2. Although GFP fusions for bioprocess monitoring have been
      demonstrated in other hosts, this is its first use in P. pastoris.

PMID- 15266124
TI  - Combining induced mutation and protoplasting for strain improvement of
      Aspergillus oryzae for kojic acid production.
AB  - By combining induced mutation, using NTG and UV irradiation, and protoplasting of
      a wild type strain of Aspergillus oryzae ATCC 22788, a hyper-producing strain was
      obtained that accumulated 41 g kojic acid l(-1) in shake-flasks, which was 100
      fold higher than that in the wild type strains. Similar production of kojic acid
      was obtained in 5 l stirred-tank fermentations.

PMID- 15266125
TI  - Neutral density liquid formulations for nematode-based biopesticides.
AB  - Entomopathogenic nematodes are widely used as biological insecticides for
      agricultural and horticultural pests. In the vast majority of cases, commercial
      products contain nematodes partially dehydrated on to inert solid carriers.
      Nematode survival in these products is generally poor, they are difficult to
      handle and are not suitable for use with all nematode species. We have developed
      a non-viscous, non-adhesive and non-toxic liquid formulation for nematode storage
      and transport based on neutral density colloidal silica suspensions. Survival and
      virulence of nematodes stored in this formulation without aeration was superior
      to nematodes stored in aerated quarter strength Ringer's solution.

PMID- 15266127
TI  - [Cancer epigenetics].
AB  - Knowledge regarding molecular events of cancer development has been rapidly
      accumulated during the last decade. The discovery of tumor suppressor gene
      silencing by aberrant promoter CpG island hypermethylation and histone-directed
      chromatin remodeling has led epigenetics to its recognition as an important
      alternative mechanism for carcinogenesis. Epigenetics does not involve changes in
      nucleotide sequences, but it affects on genetic composition in many ways. Cancer
      cells integratively co-opt genetic and epigenetic mechanisms to acquire different
      aspects of carcinogenetic phenotypes. Since epigenetic changes can be reversed
      with relative ease, the research of cancer epigenetics provides great potential
      for new therapeutic regimens.

PMID- 15266126
TI  - Co-expression of bacterial hemoglobin overrides high glucose-induced repression
      of foreign protein expression in Escherichia coli W3110.
AB  - Co-expression of Vitreoscilla hemoglobin (VHb) can enhance production of foreign
      proteins in several microorganisms, including Escherichia coli. Production of
      foreign proteins [green fluorescent protein (GFP) and organophosphorous hydrolase
      (OPH)] has been examined in two typical industrial E. coli strains, W3110 (a K12
      derivative) and BL21 (a B derivative). In particular, we investigated the effects
      of VHb co-expression and media glucose concentration on target protein
      production. We employed the nar O(2)-dependent promoter for self-tuning of VHb
      expression based on the natural changes in dissolved O(2) levels over the
      duration of culture. Foreign protein production in strain BL21 was decreased by a
      high glucose concentration but co-expression of VHb had no effect on this. In
      contrast, co-expression of VHb in strain W3110 overrode the glucose-induced
      repression and resulted in steady expression of foreign proteins.

PMID- 15266128
TI  - [The effect of non-steroidal anti-inflammatory drugs in upper gastrointestinal
      bleeding].
AB  - BACKGROUND/AIMS: To evaluate the association between non-steroidal anti
      inflammatory drugs (NSAIDs) use and upper gastrointestinal (UGI) bleeding, we
      performed a case-control study at the six University affiliated hospitals for one
      year. METHODS: Case and control subjects matched for age and sex were selected by
      endoscopy. Subjects were asked for the use of NSAIDs, past medical history,
      history of other medications, and smoking. The age and sex adjusted risk for UGI
      bleeding with NSAIDs use was compared between the case and control groups.
      RESULTS: The odd ratios of UGI bleeding with NSAIDs intake adjusted for past
      medical and medication history, past medical history only, and medication history
      only were 5.0, 5.0, and 1.7, respectively. The cases had significantly more
      history of NSAIDs intake, more diseases in medical history, and more medications
      other than NSAIDs compared to the controls. There was no relationship between UGI
      bleeding and concomitant medications in the both groups. CONCLUSIONS: This
      multicenter study suggests that a history of NSAIDs intake is strongly associated
      with UGI bleeding in Korea.

PMID- 15266129
TI  - Rate and predictive factors of rebleeding with obscure-overt gastrointestinal
      bleeding.
AB  - BACKGROUND/AIMS: Little information is available on the rate and predictive
      factors of rebleeding of unknown cause, which is very important in deciding
      further investigations on obscure-overt gastrointestinal bleeding. The aim of
      this study was to evaluate the rebleeding rate and related factors in obscure
      overt gastrointestinal bleeding patients who revealed normal gastroscopic and
      colonoscopic findings. METHODS: A total of 69 patients with negative first-line
      gastroscopy and colonoscopy were enrolled in this study as obscure-overt
      gastrointestinal bleeding cases. The relationships between rebleeding and
      clinical characteristics were analyzed retrospectively. RESULTS: The causes of
      obscure-overt gastrointestinal bleeding were confirmed in 30 cases among the 69
      cases. Small bowel tumors (14 cases) were the most common cause, followed by
      vascular lesions (6 cases). The mean follow-up period was 28 months and
      rebleeding was noticed in 19 patients (27.5%). Among these rebleeding patients,
      14 cases (73.7%) occurred within 6 months. The past experience of previous
      bleeding was significantly related with rebleeding (p=0.0009). CONCLUSIONS: Close
      observation and detailed investigations are needed for obscure-overt
      gastrointestinal bleeding patients with bleeding history, especially during 6
      months follow-up.

PMID- 15266130
TI  - [The role of interleukin-1beta gene polymorphism in the gastric carcinogenesis].
AB  - BACKGROUND/AIMS: This study was aimed to investigate the polymorphism of
      interleukin-1beta(IL-1B) and IL-1 receptor antagonist (IL-1RN) gene and the
      relationship between genotypes and development of gastric adenocarcinoma in
      Korean, and to investigate the role of Helicobacter pylori (H. pylori) infection.
      METHODS: The study population comprised of 258 patients with gastric
      adenocarcinoma. They were classified according to Lauren's classification and the
      status of H. pylori infection. Genomic DNA was extracted from the gastric tissue.
      As a control, genomic DNA from peripheral lymphocyte of 100 healthy individuals
      was used. The amplified products of -511 bp and -31 bp fragments in the IL-1B by
      PCR were digested by restriction enzyme and separated for RFLP. Variable number
      tandem repeats were amplified and subjected to RFLP of IL-1RN. RESULTS: There was
      no significant difference in the genotype of IL-1B-511T and IL-1B-31C between the
      adenocarcinoma group and the control group. IL-1RN allele 1 homozygote in the
      intestinal type showed high frequency of 91.7% (p=0.007). In the H. pylori
      positive group of the adenocarcinoma, the frequency of IL-1B-31C was
      significantly higher than that of H. pylori-negative group (p=0.045).
      CONCLUSIONS: The single nucleotide polymorphism of IL-1B-31C may contribute to
      the development of the gastric adenocarcinoma in the H. pylori-positive
      population.

PMID- 15266131
TI  - [Effect of ear mushroom (Auricularia) on functional constipation].
AB  - BACKGROUND/AIMS: Constipation is one of the most prevalent gastrointestinal
      complaints. High fiber intake is recommended as an initial therapy for
      constipation. Ear mushroom is known to have higher fiber contents about 50% than
      other mushroom. The aim of this study was to evaluate the effect of fiber
      supplements using ear mushrooms on the improvement of functional constipation.
      METHODS: We conducted a double blind study with 3 groups (placebo, ear mushrooms
      alone, and ear mushrooms with additives including cascara sagrada, etc.), which
      were randomly assigned out of 34 patients with functional constipation, defined
      by modified Rome II criteria. Number of bowel movement, straining, sense of
      incomplete evacuation, stool consistency, satisfactory relief, abdominal
      pain/discomfort and colon transit time were evaluated and analyzed before, during
      and after the treatment. RESULTS: Both ear mushrooms alone and ear mushrooms with
      additives significantly improved number of bowel movement, straining, sense of
      incomplete evacuation, stool consistency and satisfactory relief in patients with
      functional chronic constipation (p<0.05). Although the use of ear mushrooms with
      additives was found to be more effective on the improvement of constipation than
      ear mushrooms alone, it may induce abdominal discomfort or pain. CONCLUSIONS: In
      patients with functional constipation, fiber supplements using ear mushrooms
      significantly improved constipation related symptoms without serious side effect.

PMID- 15266132
TI  - [Incidence of gallbladder stones in renal transplant recipients].
AB  - BACKGROUND/AIMS: Gallbladder stone is one of the major cause of morbidity in
      adults. Renal transplantation has been found to increase the risk of gallbladder
      stone formation. The real incidence of gallbladder stones in renal transplant
      recipients is not exactly known. We performed this study to identify the risk
      factors for cholecystolithiasis. METHODS: We compared the prevalence of
      gallbladder stone in 222 renal transplantation patients with that in 222 age and
      sex matched controls. Patients who had chronic liver disease, renal disease, and
      diabetes were excluded from the control group. RESULTS: In our study, the
      incidence of gallbladder stones is 8.6% (19/222 patients) in renal
      transplantation patients, which was significantly higher than 3.60% (8/222
      control) in the control group (p=0.029). In the most of our renal transplantation
      patients, cholecystolithiasis was asymptomatic. We did not find a difference in
      age, sex, duration after transplantation, causes of renal failure, resistance
      index between patients with and without gallbladder stones in renal
      transplantation patients. CONCLUSIONS: Our results suggest that the incidence of
      gallbladder stones is higher in renal transplant recipients than non-transplant
      population in Korea. Further studies will be needed to focus the factors
      contributing to the gallbladder stone formation after renal transplantation,
      especially in regard to immunosuppressive drugs.

PMID- 15266133
TI  - [A case of mucinous gastric adenocarcinoma as submucosal tumor].
AB  - Gastric mucinous adenocarcinoma is a rare histologic subtype of gastric cancers.
      It has been reported that the gross or endoscopic finding of mucinous gastric
      carcinoma is commonly described as a ulcerative or fungating mass in common.
      There has been controversy over the prognosis and the gross morphology of
      mucinous gastric adenocarcinoma. We report a case of mucinous gastric
      adenocarcinoma presenting as a submucosal tumor.

PMID- 15266134
TI  - [Prophylactic effect of Lactobacillus GG in animal colitis and its effect on
      cytokine secretion and mucin gene expressions].

PMID- 15266135
TI  - [Role of COX-2 and PPAR in gastric carcinogenesis].

PMID- 15266137
TI  - The lacrimal paradox: toward a greater understanding of success in lacrimal
      surgery.

PMID- 15266138
TI  - Eyelid metrics.

PMID- 15266139
TI  - Endoscopic pretrichial brow lift: surgical indications, technique and outcomes.
AB  - PURPOSE: To present an alternative technique for rejuvenating the upper face of
      patients with high hairlines. METHODS: A chart review was performed to ascertain
      the longevity and aesthetic quality of endoscopically assisted pretrichial brow
      lifts. The charts of a single surgeon were reviewed (2000 to 2003). The technique
      was noted to be consistent, and in the majority of cases, additive to other
      concurrent procedures. Morbidity was defined as asymmetry, poor longevity, and
      patient dissatisfaction. All patients were included who had the procedure
      performed. No exclusions were recognized for race, age, gender, medical history,
      or any other patient demographic. RESULTS: Results for the clinical outcome were
      graded as excellent, good, fair, or poor. Subjective and objective assessments
      were made by using history, examination, and photos. A rating of excellent
      incorporates symmetry, longevity, smoothness of the brow skin, and patient
      satisfaction both with the recovery process and with the results. CONCLUSIONS: In
      properly selected cosmetic patients, the endoscopic pretrichial brow lift is an
      effective method for rejuvenating the upper face. A more youthful appearance is
      achieved with the procedure, and it is easily combined with eyelid rejuvenation.
      We believe that this technique is the procedure of choice for addressing brow
      ptosis in patients with high hairlines.

PMID- 15266141
TI  - Safety of unwrapped spherical orbital implants.
AB  - PURPOSE: To determine the exposure rate of unwrapped spherical orbital implants
      after enucleation surgery. METHODS: Retrospective review of consecutive case
      series. All patients undergoing orbital implantation during enucleation surgery
      from October 1999 to September 2003 were included. Charts were reviewed for
      preoperative diagnoses, type and size of implant, use of a wrapping material, and
      complications. RESULTS: Twenty-six consecutive patients underwent enucleation
      surgery without wrapping material. Nineteen patients received porous
      polyethylene, 5 patients received polymethylmethacrylate, and 2 received
      hydroxyapatite. Mean implant diameter was 21.03 mm. Mean follow-up was 17.1
      months (range, 2 to 43 months). There were no complications of implant extrusion,
      exposure, infection, or migration. CONCLUSIONS: The use of unwrapped spherical
      orbital implants may be associated with a low rate of early exposure. Careful
      choice of implant type may help reduce the risk of implant exposure.

PMID- 15266140
TI  - Current trends in managing the anophthalmic socket after primary enucleation and
      evisceration.
AB  - PURPOSE: To evaluate current trends in the management of the anophthalmic socket
      after primary enucleation and evisceration. METHODS: The active membership of the
      American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) was
      surveyed regarding primary enucleations and eviscerations performed between
      January and December 2002. Survey questions included practice demographics,
      orbital implant use, wrapping materials, placement of a motility peg, reasons for
      implant choice, and complications encountered. RESULTS: A total of 2,779 primary
      orbital implants were reported, comprising 1,919 (69.1%) enucleations and 860
      (30.9%) eviscerations. The high-density porous polyethylene implant was used most
      frequently for enucleations (42.7%), followed by coralline hydroxyapatite (27.3%)
      and nonporous alloplastic implants (19.9%). For eviscerations, the high-density
      porous polyethylene implant was the most commonly used implant (42.3%), followed
      by hydroxyapatite (25.9%) and nonporous alloplastic implants (25.7%). The top 3
      reasons for implant choice were outcome (69.3%), cost (43.6%), and experience
      (39.5%). Most implants were either not wrapped (59.8%) or were wrapped in donor
      sclera (25.2%) or polyglactin mesh (7.2%). Pegs were used in 8.1% of all implants
      reported. The most frequent complications encountered for unpegged implants were
      exposure (3.2%) and infection (0.4%). For pegged implants, the most common
      complications reported were pyogenic granuloma (13.7%), exposure (5.7%), and
      discharge (5.7%). CONCLUSIONS: In managing the anophthalmic socket, ASOPRS survey
      respondents preferred to use the porous polyethylene implant after primary
      enucleation and evisceration. Most orbital implants were not wrapped, and most
      surgeons preferred not to place a motility post or peg in the implant.

PMID- 15266142
TI  - Clinicopathologic analysis of 15 explanted hydroxyapatite implants.
AB  - PURPOSE: To report the clinical findings, treatment, outcomes, and
      histopathologic findings in patients with suspected orbital implant infection
      requiring implant removal. METHODS: Retrospective, observational case series of
      14 patients (15 hydroxyapatite orbital implants) undergoing implant removal from
      September 1994 through December 2002. Patient age, type of surgery, implant type,
      symptoms, treatment, histopathology of implant, and follow-up course were
      analyzed. RESULTS: Of the 14 patients, 7 were female and 7 were male. The mean
      age at explantation was 42 years. The most common symptoms were discharge and
      socket tenderness. The most common signs were conjunctival inflammation (edema,
      hyperemia), discharge, and recurrent pyogenic granuloma. Clinical evidence of
      infection was documented in 13 patients. Histopathologic assessment of the 15
      explanted implants showed acute inflammation and necrosis (abscess) with
      identification of microorganisms (5 patients), acute inflammation and necrosis
      without identification of microorganisms (4 patients), chronic inflammation with
      identification of microorganisms (1 patient), chronic inflammation without
      identification of microorganisms (3 patients), and a predominant foreign body
      granulomatous response without identification of microorganisms (2 patients).
      Osseous metaplasia was seen in 10 implants. Prompt resolution of symptoms and
      signs occurred in all but one case. CONCLUSIONS: The clinical course of porous
      orbital implant infection may be prolonged, and the early symptom of recurrent
      discharge, a common problem for implant recipients, may delay diagnosis. Implant
      infection should be suspected when there is persistent conjunctival inflammation
      and discharge after implant placement despite antibiotic therapy, discomfort on
      implant palpation, and recurrent pyogenic granuloma (indicative of implant
      exposure). Implant removal is usually required in these cases. If orbital pain
      (not necessarily related to implant palpation) is the main complaint, without
      signs of conjunctival inflammation and with or without discharge, one should
      consider other reasons for the symptoms.

PMID- 15266144
TI  - Orbital involvement in juvenile nasopharyngeal angiofibroma: prevalence and
      treatment.
AB  - PURPOSE: To assess the prevalence of orbital invasion by juvenile
      nasoangiofibroma and to discuss its surgical treatment. METHODS: A retrospective
      review of the medical records and tomographic scans of a case series of 19
      patients with juvenile nasoangiofibroma was performed. All scans were reviewed by
      a radiologist and an orbital surgeon. The presence of the tumor was assessed in
      the pterygopalatine fossa, nasal cavity, nasopharynx, paranasal sinuses, inferior
      orbital fissure, orbit, and middle cranial fossa. RESULTS: The most common
      structures invaded were pterygopalatine fossa (100%), nasal cavity (94.7%),
      sphenoid sinus (84.2%), and nasopharynx (73.7%). The orbit was invaded in 6
      (31.6%) patients. In 5 of these patients, the tumor extended in the orbit through
      the inferior orbital fissure. Four patients with orbital invasion were
      successfully operated with the Le Fort I approach. CONCLUSIONS: Orbital
      involvement is relatively common in the setting of juvenile nasoangiofibroma
      extension. The main route of orbital invasion is the inferior orbital fissure.
      The Le Fort I osteotomy is an adequate approach for managing juvenile
      nasoangiofibroma when it invades the orbit.

PMID- 15266143
TI  - Experience with sentinel lymph node biopsy for eyelid and conjunctival
      malignancies at a cancer center.
AB  - PURPOSE: To describe one center's experience with sentinel lymph node (SLN)
      biopsy in patients with eyelid and conjunctival malignancies performed with a
      smaller volume of technetium than was initially used and a small incision
      directly overlying the sentinel node(s). METHODS: A noncomparative interventional
      case series of 13 patients with clinically negative regional lymph nodes who
      underwent SLN biopsy for eyelid or conjunctival malignancies at The University of
      Texas M. D. Anderson Cancer Center between May 2002 and July 2003. Preoperative
      lymphoscintigraphy was performed with an injection of 0.3 mCi of technetium Tc
      99m sulfur colloid in a volume of 0.2 mL. Images were taken as soon as the first
      SLN was detected through the gamma camera. Intraoperative mapping was performed
      with the same volume and concentration of technetium Tc-99m sulfur colloid along
      with an injection of isosulfan blue dye. RESULTS: Five patients had conjunctival
      melanoma, 6 had sebaceous cell carcinoma of the eyelid, and 2 had eyelid
      melanoma. SLN(s) were identified in all patients. In 12 patients, more than 1 SLN
      was identified. During surgery, no SLNs were blue. One patient with conjunctival
      melanoma had an SLN that was positive on histologic examination. There were no
      ocular or extraocular complications from the procedure except for mild temporary
      weakness of the marginal mandibular branch of the facial nerve in 2 patients that
      resolved completely within 4 to 6 weeks and without any further intervention.
      None of the patients had permanent blue tattooing of the conjunctival surface or
      eyelid skin. CONCLUSIONS: Our experience suggests that lymphoscintigraphy and SLN
      biopsy with a small volume of technetium Tc-99m sulfur colloid and small
      incisions, even without the use of the blue dye, can identify SLNs in patients
      with conjunctival and eyelid malignancies, and can be performed safely.

PMID- 15266145
TI  - Pre-Whitnall levator recession with hang-back sutures in Graves orbitopathy.
AB  - PURPOSE: To describe a technique for lengthening the levator palpebrae muscle at
      the level of the transverse orbital ligament (Whitnall ligament) by using hang
      back sutures in cases of upper eyelid retraction in Graves orbitopathy, and to
      report its results. METHODS: A cohort of consecutive patients undergoing this
      procedure by a single surgeon was analyzed. The surgical technique involved
      division of the levator muscle high up, at the level of the transverse orbital
      ligament, with lengthening of the muscle by a graded amount with the use of
      nonabsorbable hang-back sutures. The length of the sutures was twice the amount
      of desired lowering of the eyelid. RESULTS: Surgery was performed on 38 eyelids
      of 21 patients. The mean preoperative eyelid retraction was 4.7 mm (range, 3 mm
      to 8 mm). Thirty-two eyelids (84%) were within 1 mm of the desired postoperative
      position. One patient required reoperation for significant undercorrection (2
      eyelids), another 4 had ptosis repairs for overcorrection (5 eyelids, one of
      which was only 1-mm overcorrected). One eyelid required medial contour repair,
      but none needed lateral contour correction. CONCLUSIONS: This procedure gives a
      relatively predictable result in patients with moderate to severe upper eyelid
      retraction and avoids the postoperative complication of contour deformities,
      especially lateral flare.

PMID- 15266146
TI  - Ultrasound biomicroscopy of the levator aponeurosis in congenital and aponeurotic
      blepharoptosis.
AB  - PURPOSE: To evaluate and measure the thickness of the levator aponeurosis by
      ultrasound biomicroscopy in congenital dysmyogenic and aponeurotic
      blepharoptosis. METHODS: Forty-four upper eyelids of 22 patients who had
      unilateral blepharoptosis were evaluated by ultrasound biomicroscopy. The
      patients ranged in age from 13 to 69 years (mean, 35.4 +/- 20.2 years). Fourteen
      patients were male and 8 patients were female. Seven patients had congenital
      dysmyogenic blepharoptosis and 15 patients had aponeurotic blepharoptosis.
      Imaging was performed with a 50-MHz transducer. The thickness of the levator
      aponeurosis was measured centrally at the upper border of the tarsus. RESULTS:
      The levator aponeurosis was imaged in all eyelids except for one eyelid with
      aponeurotic blepharoptosis. The mean thickness of the levator aponeurosis was
      0.39 +/- 0.10 mm in the ptotic eyelid and 0.42 +/- 0.09 mm in the control eyelid
      of the patients with congenital dysmyogenic blepharoptosis (p = 0.043). The mean
      thickness of the levator aponeurosis was 0.26 +/- 0.05 mm in the ptotic eyelid
      and 0.36 +/- 0.04 mm in the control eyelid of the patients with aponeurotic
      blepharoptosis (p = 0.001). The thickness of the levator aponeurosis was
      correlated with the palpebral fissure height (p = 0.013, r = 0.644) in
      aponeurotic blepharoptosis. The thickness of the levator aponeurosis was
      correlated with the levator function (p = 0.033, r = 0.795) in congenital
      dysmyogenic blepharoptosis. CONCLUSIONS: The thickness of the levator aponeurosis
      can be measured with ultrasound biomicroscopy. The most common pathology in
      aponeurotic blepharoptosis is thinned-out aponeurosis. The levator aponeurosis of
      the ptotic eyelid is thinner than the normal eyelid in congenital ptosis.

PMID- 15266147
TI  - Myotoxic effects of the skeletal muscle-specific immunotoxin, ricin-mAb35, on
      orbicularis oculi muscle after eyelid injections in rabbits.
AB  - PURPOSE: The authors recently demonstrated that a single injection of the
      immunotoxin ricin-mAb35 has potent and long-lasting myotoxic effects in
      extraocular muscles. The myotoxicity of injected ricin-mAb35 was tested in the
      eyelids of rabbits to determine its potential for use in the treatment of benign
      essential blepharospasm and other dystonias. METHODS: The immunotoxin ricin-mAb35
      was injected in one eyelid of adult rabbits. After 1 week, 1 month, or 6 months,
      the rabbits were euthanized, and the eyelids were prepared for histologic
      examination of inflammatory cell infiltrate with immunohistochemical localization
      of cd11b and myosin heavy chain isoform expression. Muscle loss was quantified by
      analysis of muscle fiber cross-sectional area and total myofiber number. RESULTS:
      Within the first week after a single injection of ricin-mAb35, some edema
      developed, which resolved by the second week. Otherwise, the eyelids were normal
      in appearance. A short-lived inflammatory response was seen at 1 week, but this
      resolved 1 month after treatment. One week after injection, there was a
      significant decrease in the total number of orbicularis oculi myofibers in the
      ricin-mAb35-treated eyelids. This myofiber loss remained significant 1 month
      later and was maintained 6 months after the initial injection. CONCLUSIONS:
      Direct injection of the immunotoxin ricin-mAb35 resulted in significant, acute
      muscle loss in the orbicularis oculi of rabbits that was maintained for up to 6
      months. Physiologic studies are needed to demonstrate concomitant loss of muscle
      strength, but these results suggest that ricin-mAb35 injection holds promise as a
      muscle-weakening agent in the eyelid.

PMID- 15266148
TI  - Erasing restylane.
AB  - A 65-year-old woman received injections of Restylane, cross-linked hyaluronic
      acid, for the intended cosmetic filling of periorbital rhytids. The achieved
      result was undesirable, and the filler lasted more than 5 years. Hyaluronidase
      administered directly beneath the treated areas resulted in rapid resolution of
      the Restylane effect.

PMID- 15266149
TI  - Periocular cutaneous melanoma arising in a radiotherapy field.
AB  - A 78-year-old woman had a periocular cutaneous melanoma in the radiation field of
      a meningioma. A medial canthal melanoma arose 32 years after primary radiation
      for a sphenoid wing meningioma and 22 years after supplemental radiation for
      meningioma recurrence. Histologic sections taken from skin surrounding the
      melanoma showed widespread melanocytic atypia and 2 separate foci of melanoma in
      situ. Cutaneous melanoma can arise in a radiation field after a long latency
      period and should be considered an uncommon form of secondary malignancy.

PMID- 15266150
TI  - Trichiasis associated with prostaglandin analog use.
AB  - A previously unreported complication of the use of prostaglandin analog
      medications for glaucoma therapy is described. A patient with monocular open
      angle glaucoma had trichiasis, a condition associated with the use of a
      prostaglandin analog. The patient was treated with radiofrequency cautery and is
      now asymptomatic. The unmedicated eye remains asymptomatic to date. Increased
      lash length, thickness, and pigmentation are well-documented side effects of
      prostaglandin analog glaucoma drops. Physicians must consider this when
      prescribing these medications for patients with misdirected eyelashes.

PMID- 15266151
TI  - Renal medullary carcinoma metastatic to the orbit: a clinicopathologic report.
AB  - A 39-year-old black man with sickle cell trait presented with a rapidly
      progressive, painful proptosis of the left eye. A computed tomographic scan was
      interpreted as revealing a cavernous hemangioma. Medial orbitotomy revealed a
      hard, gray mass supranasal to the optic nerve and invading the medial rectus
      muscle. Intraoperative frozen section specimens were read initially by the
      pathologist as metastatic adenocarcinoma. On gross examination, the conspicuous
      hemorrhage, necrosis, and bright yellow color characteristic of renal cell
      carcinoma were not present. Final pathologic analysis of the orbital lesion
      revealed metastatic renal medullary cell carcinoma. The primary lesion was
      located in the right kidney. Renal medullary carcinoma is a rare tumor, often
      affecting young individuals with sickle cell trait or disease. We report the
      first confirmed case of renal medullary carcinoma metastatic to the orbit with
      orbital symptoms preceding the diagnosis of the primary tumor.

PMID- 15266152
TI  - Optic nerve sheath fenestration for intracranial hypertension associated with
      chronic inflammatory demyelinating polyneuropathy.
AB  - The authors report a case of papilledema in a 61-year-old woman with chronic
      demyelinating polyneuropathy. The cerebrospinal fluid protein level was elevated
      (2.68 to 4.51 g/L), as was the cerebro-spinal fluid opening pressure (27 to 40 cm
      H2O). A unilateral optic nerve sheath fenestration proved to be effective in
      preserving vision, and the papilledema resolved completely.

PMID- 15266153
TI  - Modified lateral orbitotomy for intact removal of orbital dumbbell dermoid cyst.
AB  - : We describe a modified lateral orbitotomy for intact removal of a dumbbell
      dermoid cyst involving the frontozygomatic suture. The clinical features and
      surgical treatment of the case are discussed.

PMID- 15266154
TI  - Adult orbital xanthogranuloma with associated adult-onset asthma.
AB  - : The authors report a case of adult orbital xanthogranuloma with associated
      adult-onset asthma in a 44-year-old man. Adult orbital xanthogranuloma was
      diagnosed on the basis of the clinical findings of bilateral, indurated, yellow
      eyelid lesions in a patient presenting with adult-onset asthma. Incisional biopsy
      of the eyelid lesions demonstrated a diffuse histiocytic infiltrate of the orbit
      and Touton giant cells without evidence of necrobiosis. Systemic evaluation
      failed to show evidence of bone lesions or paraproteinemia. When patients present
      with atypical indurated yellow eyelid lesions, a biopsy should be considered. If
      Touton giant cells are present, a systemic evaluation should be undertaken to
      rule out both Erdheim-Chester disease and necrobiotic xanthogranuloma. If no
      systemic findings are present, other than the possibility of adult-onset asthma,
      the rare entity of adult orbital xanthogranuloma should be considered.

PMID- 15266155
TI  - Dermatofibrosarcoma protuberans of the brow and eyelid.
AB  - A 60-year-old woman had a slow-growing cutaneous nodule of her left brow. After
      initial excisional biopsy, the lesion recurred within 1 week. After tissue
      diagnosis was confirmed, the recurrent mass was excised under frozen section
      control and the defect was reconstructed with a forehead flap. This unusual tumor
      involved the brow and eyelid, down to the level of the orbital septum. The
      patient remains free of disease after 20 months.

PMID- 15266156
TI  - Enlarged extraocular muscles as the presenting feature of acromegaly.
AB  - : The authors report the case of a 32-year-old woman who presented with bilateral
      lower eyelid swelling and extraocular muscle enlargement as the initial
      manifestation of acromegaly. The acromegaly, however, was not diagnosed until 6
      years after her symptoms began. Acromegaly should be entertained in the
      differential diagnosis of any patient who presents with bilateral, symmetrical
      extraocular muscle enlargement on computed tomographic scan, especially in the
      patient with normal thyroid hormone levels and no clinical findings associated
      with thyroid orbitopathy.

PMID- 15266157
TI  - Open peer review: a first step.

PMID- 15266158
TI  - Importance of intraoperative factors to extubation outcomes.

PMID- 15266160
TI  - Post-traumatic stress disorder due to childbirth: the aftermath.
AB  - BACKGROUND: Childbirth qualifies as an extreme traumatic stressor that can result
      in post-traumatic stress disorder. The reported prevalence of post-traumatic
      stress disorder after childbirth ranges from 1.5% to 6%. OBJECTIVE: The aim of
      this phenomenologic study was to describe the essence of mothers' experiences of
      post-traumatic stress disorder after childbirth. METHODS: The qualitative
      research design used for this study was descriptive phenomenology. The main
      recruitment approach was via the Internet through the help of Trauma and Birth
      Stress, a charitable trust in New Zealand. Purposive sampling was used and
      resulted in 38 mothers participating from the countries of New Zealand, the
      United States, Australia, and the United Kingdom. The participants were asked to
      describe their experiences with post-traumatic stress disorder after childbirth.
      Their stories were analyzed using Colaizzi's method of data analysis. RESULTS:
      Mothers with post-traumatic stress disorder attributable to childbirth struggle
      to survive each day while battling terrifying nightmares and flashbacks of the
      birth, anger, anxiety, depression, and painful isolation from the world of
      motherhood. CONCLUSIONS: This glimpse into the lives of mothers with post
      traumatic stress disorder attributable to childbirth provides an impetus to
      increase research efforts in this neglected area.

PMID- 15266161
TI  - Treatment-seeking delay among women with acute myocardial infarction: decision
      trajectories and their predictors.
AB  - BACKGROUND: Women's delay in seeking treatment for acute myocardial infarction
      symptoms results in higher rates of mortality and morbidity for women.
      OBJECTIVES: To describe decision trajectories used by women when experiencing
      symptoms of acute myocardial infarction, and to identify predictors of the
      decision trajectory used by women with acute myocardial infarction. METHODS: A
      cross-sectional, descriptive design was used. The nonprobability sample included
      52 women hospitalized for acute myocardial infarction. To elicit descriptions of
      decision making, focused, semistructured interviews were used in this mixed
      methods study. Predictors of decision trajectories were measured with
      standardized instruments among the same women. Narrative analysis was used to
      examine the stories from the qualitative data and to identify decision trajectory
      types. Discriminant analysis was used to predict trajectory type membership.
      RESULTS: The median delay time was 4.25 hours. Most of the women used one of two
      trajectory types: knowing (defined as those women who knew almost immediately
      that they would seek help, n = 25) and managing (those women who managed an
      alternative hypothesis or minimized their symptoms, n = 23). Discriminant
      analysis correctly classified 71% (chi [4] = 11.2; n = 48; p =.02) of the cases
      into trajectory types on the basis of four predictor variables: social support,
      personal control, heart disease threat, and neuroticism. DISCUSSION: Women's
      behaviors during the period between onset of acute myocardial infarction symptoms
      and treatment seeking can be categorized into a small number of patterns termed
      decision trajectories. A profile of sociostructural and intrapersonal factors
      with potential for predicting behavior in relation to future coronary events was
      developed.

PMID- 15266162
TI  - Inclusion of women in nursing research: 1995-2001.
AB  - BACKGROUND: Although the inclusion of women in research has been examined in
      medical publications, little is known about how federal mandates have influenced
      the inclusion of women in research published in nursing journals. OBJECTIVE: This
      study aimed to examine the inclusion of women in published nursing research from
      1995 to 2001, with a focus on the leading causes of mortality. METHOD: All the
      articles in each journal were reviewed, and all the research articles that
      focused on the top 10 causes of death were sampled to measure the inclusion of
      women, the characteristics of the women included, the funding source, and the
      topic. RESULTS: Of the 1,149 studies reviewed, 139 met the inclusion criteria,
      and 117 of these studies included women. Only 15 of the studies reported the age
      of the women in their samples, and 10 of these included women between the ages of
      35 and 64 years. The most frequently reported race was White (n = 21), followed
      by African American (n = 17), Hispanic (n = 6), and Asian (n = 2). There were no
      associations among year of publication (p =.62), federal funding (p =.30), and
      inclusion of women. Among the studies including women, heart disease was the most
      frequent topic (n = 52), followed by Alzheimer's disease (n = 21), cancer (n =
      14), respiratory illness (n = 14), and diabetes (n = 8). DISCUSSION: Although the
      majority of the research included women, continuing efforts must be made to
      include sufficient numbers of women.

PMID- 15266163
TI  - The transtheoretical model of behavior change and smokers in southern Appalachia.
AB  - BACKGROUND: The southern Appalachian states show a high prevalence of smoking,
      with associated high rates of both heart disease and cancer, yet cultural
      differences raise questions concerning the applicability of the most frequently
      used model for smoking cessation, the transtheoretical model, for smokers from
      this region of the country. OBJECTIVE: To identify, by examining the
      applicability of the transtheoretical model for southern Appalachian smokers, the
      percentage of individuals in each of the five stages of change, the use of the
      processes of change from the trans-theoretical model, and the scores on
      recognized predictors of smoking cessation including the temptation to smoke, the
      perceived barriers to cessation, the pros and cons of smoking, and nicotine
      dependence. METHODS: This population-based, descriptive, cross-sectional study
      used a random sample of 3,800 telephone numbers, which were called up to eight
      times. The 659 smokers or former smokers who agreed to participate were mailed a
      written questionnaire consisting of six well-established scales that measure
      constructs from the transtheoretical model. The final sample consisted of 357
      usable questionnaires. RESULTS: The distribution of smokers in northeastern
      Tennessee differed from national samples across the first three stages of change,
      with 56% in precontemplation, as compared with previous findings of 40% in
      national samples. The subjects' scores for the pros of smoking were similar
      across the stages of change in this sample, and although the scores for the cons
      differed significantly across the stages in the sample, post hoc analysis
      indicated that the only significant change occurred between precontemplation and
      contemplation. The scores for temptation to smoke did not differ significantly
      across the stages of change in this sample. DISCUSSION: Smokers from Appalachian
      Tennessee differ from smokers in other parts of the United States, and these
      findings raise questions about the applicability of the transtheoretical model
      for this population.

PMID- 15266164
TI  - Depression among southern rural African American women: a factor analysis of the
      Beck Depression Inventory-II.
AB  - BACKGROUND: This is the first reported study involving a factor analysis of the
      Beck Depression Inventory-II, which was administered to a sample of southern
      rural African American women. OBJECTIVE: To determine the factor structure of the
      Beck Depression Inventory-II using data collected from southern rural African
      American women. METHODS: Using a correlational, descriptive design, 206 southern
      rural African American women were invited to participate in a face-to-face
      interview that occurred in a variety of community-based settings. RESULTS: The
      factor analysis of the Beck Depression Inventory-II resulted in a two-factor
      solution. Symptoms such as pessimism and worthlessness loaded high on the first
      factor (cognitive). The second factor explained somatic-affective symptoms of
      depression, with factor loadings high on tiredness and fatigue and loss of
      energy. CONCLUSIONS: The application of the Beck Depression Inventory-II among
      African American people would generate needed information about how depressive
      symptoms may be expressed among them. Knowledge gained from this study promises
      to be useful for developing appropriate research studies and population-specific
      treatment approaches for this group of women.

PMID- 15266165
TI  - The Minimum Data Set bedfast quality indicator: differences among nursing homes.
AB  - BACKGROUND: Excessive time in bed has negative effects on both physical
      conditioning and functioning. There are no data or practice guidelines relevant
      to how nurses should manage the in-bed times of nursing home residents, although
      all nursing homes receive a bedfast prevalence quality indicator report generated
      from the Minimum Data Set. OBJECTIVES: To compare nursing homes that score in the
      upper and lower quartiles on the Minimum Data Set bedfast prevalence quality
      indicator for proportion of bedfast residents, activity and mobility nursing
      care, and amount of time all residents spend in bed, and to evaluate whether
      residents who spend more time in bed are different from those who spend less time
      in bed according to functional measures. METHODS: A cohort design used medical
      records, resident interviews, and direct observation data to compare 15 nursing
      homes (n = 451 residents) on the proportion of bedfast residents, the amount of
      time residents spent in bed, the frequency of activity, and the scores on six
      activity and mobility care process indicators. RESULTS: Significant differences
      were found between upper (i.e., higher prevalence of bedfast residents) and lower
      quartile nursing homes in the proportion of time residents were observed in bed
      (43% vs. 34%, respectively; p =.007), and in the proportion of residents who
      spent more than 22 hours in bed per day (18% vs. 8%, respectively; p =.002). All
      nursing homes underestimated the number of bedfast residents. The residents of
      upper quartile homes showed more activity episodes and reported receiving more
      walking assistance than the residents of lower quartile homes. DISCUSSION:
      Minimum Data Set bedfast quality indicator identified nursing homes in which
      residents spent more time in bed, but did not reflect differences in activity and
      mobility care. In fact, upper quartile homes provided more activity and mobility
      care than lower quartile homes. Across all the nursing homes, most of the
      residents spent at least 17 hours a day in bed. Further study of activity and
      mobility care and bedfast outcomes in nursing homes is needed, and nurses need to
      note the amount of time nursing home residents spend in bed.

PMID- 15266166
TI  - Research partners: two teams, one study population.
AB  - BACKGROUND: Two large research projects funded by the National Institutes of
      Health, the Disease Management project and the Thrive study, which examine
      different phenomena in the chronically critically ill population, have combined
      research teams. Each study has its own project manager and maintains a separate
      database and budget. Operational tasks for both grants are streamlined through
      the collaboration and cross-training of all team members. METHODS: The Disease
      Management project is a randomized clinical trial testing the effectiveness of a
      care program in improving outcomes for chronically critically ill patients and
      their caregivers during the first 2 months after discharge. The Thrive study is a
      prospective longitudinal investigation that aims to describe the weaning patterns
      of chronically critically ill patients as well as the patterns of illness-related
      variables. RESULTS: To date, many participants (n = 400) have been enrolled in
      each study. The results of both studies will be available through future
      publications. CONCLUSIONS: Although much information has been gleaned from
      gathering longitudinal data across one study population and examining two rich
      data sets, there are some limitations to this collaboration.

PMID- 15266167
TI  - Trier Social Stress Test: a method for use in nursing research.
AB  - BACKGROUND: Researchers face the difficulty of inducing psychosocial stress in a
      laboratory setting using a method that institutional review boards could consider
      an acceptable research protocol. METHODS: This article describes the Trier Social
      Stress Test, a research protocol that can be used to induce psychosocial stress
      and capture the integrated aspects of an individual's biologic and psychological
      responses. RESULTS: The test involves 15 minutes of psychosocial stress induced
      by a mock job interview and followed by a mental arithmetic challenge before a
      panel of three judges. The discomfort associated with performance requirements
      induces stress in socially acceptable ways that can be measured using physiologic
      and/or psychological parameters. CONCLUSIONS: This method allows stress to be
      induced and measured in a controlled, laboratory setting.

PMID- 15266168
TI  - The new BNMS guidelines for measurement of glomerular filtration rate.

PMID- 15266169
TI  - Guidelines for the measurement of glomerular filtration rate using plasma
      sampling.
AB  - These guidelines have been adopted by the British Nuclear Medicine Society.

PMID- 15266170
TI  - Audit of nuclear medicine scientific and technical standards.
AB  - The British Nuclear Medicine Society has developed a process for the service
      specific organizational audit of nuclear medicine departments. This process
      identified the need for a scheme suitable for the audit of the scientific and
      technical standards of a department providing such a service. This document has
      evolved following audit visits of a number of UK departments. It is intended to
      be used as a written document to facilitate the audit procedure and may be used
      for both external and self-audit purposes. Scientific and technical standards
      have been derived from a number of sources, including regulatory documents, notes
      for guidance and peer-reviewed publications. The audit scheme is presented as a
      series of questions with responses graded according to legal and safety
      obligations (A), good practice (B) and desirable aspects of service delivery (C).
      This document should be regarded as part of an audit framework and should be kept
      under review as the process evolves to meet the future demands of this high
      technology-based clinical service.

PMID- 15266171
TI  - 99mTc tetrofosmin scintigraphy in acute leukaemia: the relationship between
      marrow uptake of tetrofosmin and P-glycoprotein and chemotherapy response.
AB  - BACKGROUND: The non-invasive detection of P-glycoprotein (Pgp) and multidrug
      resistance related proteins in vivo, will represent the greatest challenge in
      overcoming multidrug resistance. Although 99mTc tetrofosmin has been used
      previously as a myocardial perfusion agent, it is now also being used in the
      imaging of various tumours. In the current study, Tc tetrofosmin was used in the
      investigation of acute leukaemia. AIM: To show the uptake pattern of 99mTc
      tetrofosmin in the bone marrow of patients with acute leukaemia, and to ascertain
      the relationship between 99mTc tetrofosmin uptake and the level of Pgp expression
      and their relation to the response to chemotherapy. In addition, CD95, which is
      an indicator of apoptosis (programmed cell death), has also been assessed.
      MATERIALS AND METHODS: Pgp and CD95 were detected by using flow cytometry. Of the
      27 acute leukaemia patients assessed, nine had previously received chemotherapy,
      and 18 had had an initial diagnosis. All patients had undergone 99mTc tetrofosmin
      scintigraphy, and their Pgp and CD95 levels had been determined. The same
      parameters were studied again for 14 patients. The responses to chemotherapy were
      assessed by patients' clinicians. A control group of 37 patients without bone
      marrow pathology was also studied in order to provide comparisons for the
      scintigraphy results. The control images were assessed only qualitatively.
      RESULTS: In leukaemia patients the uptake of 99mTc tetrofosmin into bone marrow
      was found to be considerably higher than in control patients (P=0.000). An
      analysis of the relationship between Pgp, CD95, and the qualitative and
      quantitative tetrofosmin uptake ratios (URs) showed that there was an inverse
      correlation only between Pgp and the quantitative uptake ratio (P=0.016, r=
      0.461). When the patients were grouped as 'good' and 'poor', as related to the
      chemotherapy response, there were no meaningful differences between these two
      groups regarding Pgp, CD95 and tetrofosmin URs (P>0.05). By evaluating the
      scintigraphic findings of the 'repeated' 14 patients, we showed that if the 99mTc
      tetrofosmin UR in the second imaging test was reduced by >0.08, the response to
      chemotherapy tended to be good. This method, based on follow-up scanning with
      tetrofosmin, showed a sensitivity of 83% and a specificity of 62% in the
      prediction of a 'good' response, if a decrease of 0.08 was taken into
      consideration. CONCLUSION: In this study, patients with acute leukaemia showed
      significant uptake of tetrofosmin into the bone marrow. The addition of basal and
      repeated 99mTc tetrofosmin scintigraphy to the management protocol for leukaemia
      could lead to the preferential determination of responses to chemotherapy, by
      evaluating whole bone marrow non-invasively. This method seems promising, but it
      needs further support from various similar investigations comprising more
      patients in order to confirm our results.

PMID- 15266172
TI  - 99mTc depreotide scan compared with 99mTc-MDP bone scintigraphy for the detection
      of bone metastases and prediction of response to hormonal treatment in patients
      with breast cancer.
AB  - BACKGROUND: The purpose of this study was to determine the potential role of Tc
      depreotide scintigraphy for the evaluation of bone metastases compared with Tc
      methylenediphosphonate (MDP) bone scintigraphy and for the prediction of
      treatment response in breast cancer patients in whom first- or second-line
      hormonal therapy was to be initiated. METHODS: Twelve patients with a diagnosis
      of advanced breast cancer were included. All patients underwent both a bone scan
      and a depreotide scan and at least one other conventional imaging procedure,
      including plain film radiography (n=11), computed tomography (n=6) or magnetic
      resonance imaging (n=5), for confirmation of metastatic disease. The mean time
      interval between the bone scan and the depreotide scan was 30.6 days. Follow-up
      data were retrieved from routine clinical evaluation by means of physical
      examination, imaging and blood analysis. RESULTS: On a patient basis we found a
      sensitivity, specificity and accuracy of, respectively 100%, 50% and 83.3% for
      the bone scan and 62.5%, 100% and 75% for the depreotide scan in the diagnosis of
      bone metastasis. In eight patients with available follow-up data two with a
      positive depreotide scan remained stable and five of six patients with a negative
      depreotide scan had progressive disease. CONCLUSION: In this small series of
      breast cancer patients Tc depreotide scintigraphy proves less sensitive but more
      specific as compared to Tc-MDP bone scintigraphy in measuring the extent of bone
      metastasis. On the other hand Tc depreotide scintigraphy elucidates, non
      invasively, tumour characteristics and may be indicative for prognosis and
      response to hormonal treatment.

PMID- 15266173
TI  - Influence of 131I diagnostic dose on subsequent ablation in patients with
      differentiated thyroid carcinoma: discrepancy between the presence of visually
      apparent stunning and the impairment of successful ablation.
AB  - BACKGROUND: In the management of patients with differentiated thyroid carcinoma,
      direct comparison of the presence of scintigraphic stunning after a diagnostic
      dose of 131I with subsequent successful ablation has not been evaluated. METHODS:
      This study included 245 patients who received a dose of 2775-3700 MBq of 131I for
      thyroid remnant ablation. In all patients, the thyroid-stimulating hormone (TSH)
      level before ablation was more than 30 microlU x ml. One hundred and twenty-six
      patients (Group A) were given a 185 MBq diagnostic scan (Dscan) 4-11 days before
      131I ablation, and 119 patients (Group B) received 131I ablation directly after
      thyroidectomy. Scintigraphic stunning was considered to be present on any post
      ablation scan that revealed either fewer foci or obviously less prominent uptake
      compared with the earlier corresponding Dscan. Successful ablation was defined as
      no visible uptake in the neck region or anywhere else on a follow-up Dscan 6-12
      months later. RESULTS: Our results revealed that only 13 of the 126 patients
      (10.3%) in Group A had visually apparent thyroid stunning. Successful ablation
      was obtained in 56 of 126 cases (44.4%) in Group A, compared with 86 of 119 cases
      (72.2%) in Group B (P<0.001). In Group A, the success rate of ablation in
      patients with stunning (5/13) was not statistically different from that in those
      without (51/113) (odds ratio, 0.76; 95% CI, 0.23-2.47). Multiple logistic
      regression analysis revealed that the independent determinants of successful
      ablation were the use of Dscan before ablation (odds ratio, 0.23; 95% CI, 0.10
      0.56) and the ablation dose of 131I (odds ratio, 1.05; 95% CI, 1.00-1.10).
      CONCLUSIONS: Visually apparent stunning is infrequent and may not be sufficiently
      sensitive to detect the influence of a 185 MBq Dscan on subsequent ablation
      outcome. For patients with differentiated thyroid carcinoma, we recommend that
      ablation should be performed directly after thyroidectomy.

PMID- 15266174
TI  - Treatment of advanced differentiated thyroid carcinoma with high activity
      radioiodine therapy.
AB  - OBJECTIVES: This was a retrospective study to assess the efficacy and morbidity
      of high activity I therapy in patients with advanced differentiated thyroid
      carcinoma. METHODS: From 1975 to 2003, 38 patients with locally advanced or
      metastatic differentiated thyroid cancer (16 follicular, 20 papillary, one
      Hurthle cell, one insular) were treated with high activity radioiodine therapy (9
      GBq) as the cancers had previously not responded to standard activities (5.5
      GBq). RESULTS: Cumulative total activities received ranged from 11.8 to 84.5 GBq
      (mean 29.4 GBq per patient). Staging at presentation showed pT4 and/or M1 disease
      in 27/38 of patients (71.1%). Moderate (grade 2) and poorly differentiated (grade
      3) tumours were present in a total of 9/38 patients (23.7%). Outcomes were
      evaluated according to the results of I whole-body scans, serum thyroglobulin,
      radiological assessments and physical examination. Neither [18F]flurodeoxyglucose
      positron emission tomography (F-FDG PET) nor 99mTc sestamibi were available
      during this study. The mean duration of follow-up was 83 months. A complete
      response was observed in 7/38 patients (18.4%), progressive disease in 27/38
      (71.1%) and stable disease in 4/38 (10.5%). The mean survival from initiation of
      high activity treatment was 36.6 months. For patients with lung disease the mean
      survival was 45 months, neck disease 38.9 months, bone disease 35 months and
      multiple sites was 30.9 months. Twelve patients died during follow-up (10 due to
      thyroid carcinoma). After high activity treatment, 9.7% of patients suffered
      grade 3 and 3.2% suffered grade 4 WHO haematological toxicity. Significant
      salivary gland morbidity was observed (30% dry mouth, 27% salivary swelling).
      CONCLUSIONS: Repeated treatment with high activity (9 GBq) I in patients with
      advanced differentiated thyroid carcinoma appears to be of no apparent benefit
      and may lead to late morbidity.

PMID- 15266175
TI  - Evaluation of human anti-mouse antibody response in normal volunteers following
      repeated injections of fanolesomab (NeutroSpec), a murine anti-CD15 IgM
      monoclonal antibody for imaging infection.
AB  - BACKGROUND: Fanolesomab (NeutroSpec) is a murine monoclonal Tc labelled anti-CD15
      IgM antibody that localizes collections of human polymorphonuclear neutrophils
      (PMNs) at sites of infection. OBJECTIVES: The objectives of this study were to
      evaluate the safety of repeated injections of fanolesomab and the extent of
      induction of human anti-mouse antibody (HAMA) response. METHODS: Thirty healthy
      adults (15 men and 15 women) were enrolled in the study. Subjects were injected
      on two separate occasions, separated by 21 days, with 125 microg of fanolesomab
      that had been labelled with decayed Tc. HAMA assays were performed on blood
      samples drawn prior to each injection, and at 7 and 28 days following the second
      injection. Safety was determined by monitoring for adverse events, and for
      changes in vital signs, physical examination and clinical laboratory
      measurements. RESULTS: Five subjects exhibited induction of HAMA (16.7%; 95% CI,
      6.3-34.2%). Two were considered marginal responses (increase from 5 to 31, and 5
      to 20 and 24 ng x ml), and three were considered moderate (7 to 228, 7 to 140 and
      270, and 7 to 35 and 450 ng x ml). There were no strong responses (greater than
      1000 ng x ml). Seven subjects experienced adverse events, most of which were
      coincidental to administration of fanolesomab. There were no serious or severe
      adverse events. CONCLUSIONS: Repeated fanolesomab injections at clinically useful
      doses does not appear to induce a strong HAMA response nor does it present a risk
      for serious adverse events.

PMID- 15266176
TI  - Diagnosis of infection of implantable central venous catheters by
      [18F]fluorodeoxyglucose positron emission tomography.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of
      [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the
      diagnosis of infection of implantable vascular catheters. METHODS: We evaluated
      six patients with haematological cancer and infection of their implantable
      vascular catheter and who underwent FDG PET imaging around the time of their
      infection. RESULTS: Six patients with multiple myeloma who developed infection of
      their implantable device (five port pocket infections and one tunnel infection)
      were identified. FDG PET revealed increased uptake at the site of the implantable
      catheter (SUV 2.7-4.5) in all six patients, even in the absence of signs or
      symptoms of infection at the site of the device (three), and the presence of
      severe neutropenia (four). The three patients who did not have local inflammation
      at the site of the device were profoundly neutropenic. The FDG PET diagnosis led
      to removal of the device in two patients. CONCLUSION: FDG PET is a safe, rapid
      and accurate tool for diagnosing infection of an implantable catheter, including
      among those patients not exhibiting local signs and symptoms of infection, and in
      whom the diagnosis of infected device may be difficult. FDG PET may help prevent
      the unnecessary removal of implantable intravascular catheters and the
      unwarranted use of antibiotics.

PMID- 15266177
TI  - Dual time point 2-[18F]fluoro-2'-deoxyglucose positron emission tomography in
      chronic bacterial osteomyelitis.
AB  - OBJECTIVE: Quantitative dual time point imaging with [F]fluorodeoxyglucose
      positron emission tomography (F-FDG PET) has recently been found to be more
      accurate than single time point scanning in the discrimination between benign
      lesions and malignancy in various conditions. In our study we investigated
      glucose metabolism in chronic bacterial osteomyelitis (COM) by using F-FDG PET
      and a dual time protocol. METHODS: Seventeen non-diabetic patients with
      histopathologically proven COM and four non-diabetic patients with malignant bone
      disease were prospectively investigated with dual time F-FDG PET. All lesions
      were detected by their increased F-FDG uptake 30 and 90 min after injection of
      370 MBq of F-FDG. The maximum and mean lesional standardized uptake values
      (SUV(max) and SUV(mean) after 30 and 90 min were determined. RESULTS: The median
      SUV(max) and SUV(mean) values of all osteomyelitic lesions at 30 min were 1.85
      (range, 0.45-3.45) and 1.1 (range, 0.21-1.99), respectively. The median SUV(max)
      and SUV(mean) values of all malignant lesions at 30 min were 3.19 (range, 2.31
      4.7) and 2.82 (range, 2.4-3.71), respectively. At 90 min the median SUV(max) and
      SUV(mean) of all osteomyelitic lesions were 1.78 (range, 0.4-2.93) and 1.1
      (range, 0.18-1.72), respectively. At the same time point the median SUV(max) and
      SUV(mean) of all malignant lesions were 4.1 (range, 3.52-5.32) and 3.34 (range,
      2.81-4.12), respectively. In osteomyelitis the SUV(max) and SUV(mean) between 30
      and 90 min post-injection remained stable or decreased in 16/17 patients. In
      these patients a median decrease of 6% for SUV(max) (range, 1-31%) and a median
      decrease of 8.5% for SUV(mean) (range, 0-24%) was observed. Changes of SUV(max)
      and SUV(mean) between 30 and 90 min were highly significant (P<0.05). In one
      patient SUV(max) and SUV(mean) increased over the time. The histology of this
      patient revealed multiple foreign body granulomas in addition to a mononuclear
      infiltrate. In malignant lesions the SUV(max) and SUV(mean) between 30 and 90 min
      post-injection increased. CONCLUSION: Our preliminary results indicate that
      dynamic dual time point F-FDG PET provides a characteristic pattern in chronic
      osteomyelitis similar to inflammatory processes in other locations. This pattern
      may be of value in the differentiation between COM and malignant bone lesions.

PMID- 15266178
TI  - The value of vesicant 18F-fluorodeoxyglucose positron emission tomography (18F
      FDG PET) in gastric malignancies.
AB  - AIM: The value of vesicant 18F-fluorodeoxyglucose positron emission tomography
      (18F-FDG PET) in the detection and staging of primary gastric malignancies was
      studied prospectively. METHODS: Thirty-eight patients with suspected gastric
      tumour were imaged with three-dimensional PET after the injection of 18F-FDG.
      During the PET study, vesicant was given orally in order to extend the stomach
      with CO(2) gas. Surgical operation (n=31) or gastric endoscopy with biopsy (n=7)
      was undertaken 3-26 days after the PET study. The PET results were compared with
      clinical (computed tomography/magnetic resonance imaging/ultrasound), surgical
      and histological staging. RESULTS: PET correctly diagnosed 83.3% of primary
      malignant (25/30) and benign (7/8) lesions, and corrected 11 clinically and five
      surgically mis-staged cases. Five primaries were false-negatives in quantitative
      analysis, but qualitative PET readings revealed positive lymph nodes, thereby
      providing a correct diagnosis in two of the five. PET misdiagnosed seven N1, one
      N2 and one false-positive case. The focal uptake of 18F-FDG was correlated with
      the differentiation, size and depth of invasion of the gastric tumours.
      CONCLUSIONS: 18F-FDG PET is useful for the detection and staging of primary
      gastric malignancies, and the administration of vesicant may improve the
      diagnostic confidence.

PMID- 15266179
TI  - Automated quantification of 99mTc sestamibi myocardial perfusion compared with
      visual analysis.
AB  - OBJECTIVES: The visual interpretation of 99mTc sestamibi single photon emission
      computed tomography (SPECT) myocardial perfusion images can be challenging due to
      the quantity of scan information generated, the large number of normal variants,
      attenuation artifacts and gender differences. The development of automated,
      computer derived, quantitative indices of perfusion can assist in this
      interpretation by providing an objective measure. It is important to verify that
      similar results can be obtained when the software is used in centres outside
      those where the algorithms were initially developed. Our objective was to assess
      the degree of concordance between the visual and automated diagnostic assessments
      of 99mTc sestamibi SPECT. METHODS: We studied 718 patients referred for 99mTc
      sestamibi SPECT myocardial perfusion imaging. The SPECT studies were initially
      interpreted visually without benefit of computer based analysis, and were then
      subjected to blinded reprocessing to extract quantitative indices of perfusion.
      RESULTS: There was very good agreement between the visual and quantitative
      diagnostic classifications. When a visual abnormality was taken to be the
      reference standard, the automated summed stress score (SSS) showed agreement
      (SSS>3) in 80% (kappa 0.60, P<0.0001). The area under the receiver operating
      characteristic (ROC) curve was 0.89 (95% confidence interval (CI), 0.86-0.91).
      Concordance was greater in those with previous myocardial infarction or severe
      perfusion defects, but was not affected by age, prior revascularization, stress
      procedure or heart rate. Concordance over the presence or absence of visual
      reversibility and the summed difference score (SDS) in abnormal scans was
      slightly lower (overall agreement 73% (kappa 0.36, P<0.00001) and ROC area 0.84
      (95% CI, 0.77-0.90)). CONCLUSION: Automated quantification of 99mTc sestamibi
      SPECT myocardial perfusion with the SSS and SDS provides objective diagnostic
      information and concordance when compared with conventional visual image
      interpretation.

PMID- 15266180
TI  - 99mTc-depreotide tumour uptake in patients with non-Hodgkin's lymphoma.
AB  - BACKGROUND: 99mTc-depreotide (NeoTect) is a synthetic somatostatin analogue,
      which binds to somatostatin receptor (SSTR) subtypes 2, 3 and 5. Imaging patients
      with non-Hodgkin's lymphoma (NHL) using the somatostatin analogue In
      pentetreotide (Octreoscan) has demonstrated the feasibility of identifying
      lymphoma sites with this class of peptide radiopharmaceutical. SSTR peptides can
      be labelled with beta emitters and, if sufficient tumour uptake relative to
      normal organs can be demonstrated, therapeutic applications can be considered.
      METHODS: In this prospective Institutional Review Board (IRB)-approved study,
      patients with NHL and a recent computed tomography (CT) examination were
      eligible. Whole-body and selected single-photon emission computed tomography
      (SPECT) imaging was performed 1 h after intravenous injection of 99mTc
      depreotide. Images were compared with CT scan findings. The radioactivity
      concentration of 99mTc-depreotide in abdominal/pelvic tumour sites, together with
      normal organs, was determined and expressed as the percentage of injected
      activity per gram of tissue (%IA x g). RESULTS: Paired CT and 99mTc-depreotide
      images for three patients with indolent and six with aggressive NHL revealed
      abnormal 99mTc-depreotide uptake corresponding to the tumour seen on CT in seven
      of these patients. In three of the patients, all known tumour sites were detected
      on 99mTc-depreotide images. The mean %IA x g for nine abdominal/pelvic tumour
      foci from four patients was found to be 0.004% (range, 0.001-0.007%). The mean
      tumour to bone marrow activity concentration ratio in these four patients was
      found to be 0.94 (range, 0.33-1.40), whereas the tumour to kidney ratio was 0.53
      (range, 0.16-0.80). CONCLUSIONS: Levels of 99mTc-depreotide in tumour suggest at
      least the possibility of potential therapy with beta emitter-labelled SSTR
      peptides; however, depreotide itself appears not to be a suitable candidate as a
      targeting agent due to the relatively high bone marrow concentration.

PMID- 15266181
TI  - Preparation and pharmaceutical evaluation for clinical application of high
      specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.
AB  - BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography
      (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the
      compound has prevented its extensive clinical application. Recently, we have
      developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study,
      we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for
      intravenous injection which is feasible for the clinical evaluation of beta
      adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2
      (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated
      using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by
      reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon
      tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed
      phase, high-performance liquid chromatography (RP-HPLC) and the radioactive
      fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S
      (-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22
      microm membrane filter. The radiochemical purity and the mass of the compound
      were determined with RP-HPLC. The residual organic solvents were determined with
      GC. Tests for sterility and the presence of bacterial endotoxins were also
      performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in
      25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific
      activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis
      (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not
      detected in the solution. The ethanol concentration was determined to be 60.3+/
      52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results.
      CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous
      injection with high purity and high specific activity, which is feasible for the
      clinical evaluation of beta-adrenoreceptors.

PMID- 15266182
TI  - A method to quantify the uptake rate of 2-[18F]fluoro-2-deoxy-D-glucose in
      tissues.
AB  - A two-compartment model is used to derive the tissue time-activity curve of 2
      [18F]fluoro-2-deoxy-D-glucose (18F-FDG). At the later phase of the 18F-FDG
      activity in the tissue, the model leads to a method which allows the assessment
      of the 18F-FDG uptake rate constant. The proposed method is both compared with
      the standard uptake value (SUV) method and with Patlak's graphical analysis.

PMID- 15266183
TI  - Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected
      for renal size.

PMID- 15266185
TI  - Evolutionary perspective on adolescent sexuality.

PMID- 15266186
TI  - Valproate-induced hyperammonemic encephalopathy.

PMID- 15266187
TI  - Zaleplon overdose associated with sleepwalking and complex behavior.

PMID- 15266188
TI  - Neuropathy due to hypovitaminosis following excessive weight loss.

PMID- 15266189
TI  - Cognitive-behavioral psychotherapy for anxiety and depressive disorders in
      children and adolescents: an evidence-based medicine review.
AB  - OBJECTIVE: To review the literature on the cognitive-behavioral treatment of
      children and adolescents with anxiety and depressive disorders within the
      conceptual framework of evidence-based medicine. METHOD: The psychiatric and
      psychological literature was systematically searched for controlled trials
      applying cognitive-behavioral treatment to pediatric anxiety and depressive
      disorders. RESULTS: For both anxiety and depression, substantial evidence
      supports the efficacy of problem-specific cognitive-behavioral interventions.
      Comparisons with wait-list, inactive control, and active control conditions
      suggest medium to large effects for symptom reduction in primary outcome domains.
      CONCLUSIONS: From an evidence-based perspective, cognitive-behavioral therapy is
      currently the treatment of choice for anxiety and depressive disorders in
      children and adolescents. Future research in this area will need to focus on
      comparing cognitive-behavioral psychotherapy with other treatments, component
      analyses, and the application of exportable protocol-driven treatments to
      divergent settings and patient populations.

PMID- 15266190
TI  - Mental health need and access to mental health services by youths involved with
      child welfare: a national survey.
AB  - OBJECTIVE: This study assessed the relationship between the need for and use of
      mental health services among a nationally representative sample of children who
      were investigated by child welfare agencies after reported maltreatment. METHOD:
      Data were collected at study entry into the National Survey of Child and
      Adolescent Well-Being and were weighted to provide population estimates. RESULTS:
      Nearly half (47.9%) of the youths aged 2 to 14 years (N = 3,803) with completed
      child welfare investigations had clinically significant emotional or behavioral
      problems. Youths with mental health need (defined by a clinical range score on
      the Child Behavior Checklist) were much more likely to receive mental health
      services than lower scoring youth; still, only one fourth of such youths received
      any specialty mental health care during the previous 12 months. Clinical need was
      related to receipt of mental health care across all age groups (odds ratio = 2.7
      3.5). In addition, for young children (2-5 years), sexual abuse (versus neglect)
      increased access to mental health services. For latency-age youths, African
      American race and living at home significantly reduced the likelihood of care.
      Adolescents living at home were also less likely to receive services, whereas
      having a parent with severe mental illness increased (odds ratio = 2.4) the
      likelihood of service use. CONCLUSIONS: Routine screening for mental health need
      and increasing access to mental health professionals for further evaluation and
      treatment should be a priority for children early in their contact with the child
      welfare system.

PMID- 15266191
TI  - The U.S. child welfare system: a de facto public behavioral health care system.

PMID- 15266192
TI  - Use of and need for professional help for emotional and behavioral problems among
      preadolescents: a prospective cohort study of 3- to 12-year-old children.
AB  - OBJECTIVE: To determine the effect of child-, parent- and family-related factors
      on the use of and need for mental health services by 12 years of age. METHOD: A
      prospective population-based questionnaire study of 1,287 first-born children was
      launched in Finland in 1985. The Child Behavior Checklist (CBCL) was completed by
      1,086 parents when the children were aged 3 years. At the age of 12, the CBCL,
      the Youth Self-Report, and other potential determinants of service need and use
      were obtained from 908 parents and 900 children (80% response rate). RESULTS: Of
      the total sample, 7.2% had used professional services, and 3.3% had needed
      services without obtaining them. Elevated scores on the age 3 CBCL Total Problems
      and Externalizing scale predicted independently later service use but not
      perceived need of services. In cross-sectional data at age 12, parental ratings
      of the child's problem behavior were associated with both the need for and use of
      services. Poor social competence and parental distress were independently
      associated with use of services. CONCLUSIONS: Recognizing behavior problems in
      early childhood and evaluating family stress factors are important in social and
      health care systems designed for children.

PMID- 15266193
TI  - Lithium treatment of acute mania in adolescents: a placebo-controlled
      discontinuation study.
AB  - OBJECTIVE: There are no published placebo-controlled studies of any agent in the
      treatment of acute mania in children or adolescents. This is the first placebo
      controlled study of lithium's efficacy in the treatment of acute mania in
      adolescents. METHOD: In this discontinuation study, participants received open
      treatment with lithium at therapeutic serum levels (mean 0.99 mEq/L) for at least
      4 weeks. Responders were randomly assigned to continue or discontinue lithium
      during a 2-week double-blind, placebo-controlled phase. This study had 80% power
      to detect a 40% difference in exacerbation rates between groups (10% on lithium
      versus 50% on placebo). RESULTS: Twenty-three of 40 protocol participants (57.5%)
      experienced a clinically significant symptom exacerbation during the 2-week
      double-blind phase. However, the slightly lower exacerbation rate in the group
      maintained on lithium (10/19 or 52.6%) versus the group switched to placebo
      (13/21 or 61.9%) did not reach statistical significance. CONCLUSIONS: This study
      does not support a large effect for lithium continuation treatment of adolescents
      with acute mania, mostly due to the unexpectedly high rate of exacerbations in
      the group that continued on lithium. Further studies are warranted to clarify
      whether acute mania in adolescents is lithium responsive.

PMID- 15266194
TI  - Family discord and stress predictors of depression and other disorders in
      adolescent children of depressed and nondepressed women.
AB  - OBJECTIVE: To test the hypothesis that family stress variables are associated
      with the effects of maternal depression on offspring diagnoses and examined
      whether such factors may be differentially associated with disorders in offspring
      of depressed and never-depressed women. METHOD: Eight hundred sixteen mothers and
      their 15-year-old children in an Australian community completed cross-sectional
      assessments of mother and youth diagnoses, interviewer-rated and self-reported
      quality of marital relationship/status, quality of parent-child relationship, and
      interviews for youth chronic and episodic stress. Women with depression histories
      were oversampled and included 458 never-depressed and 358 women with current or
      past major depressive episodes or dysthymic disorder. RESULTS: Significant
      interaction effects were found between maternal depression and family
      discord/stress variables such that high levels of environmental risk factors were
      significantly associated with youth depression in children of depressed women
      compared with low levels of adverse conditions and were generally less associated
      with depression in children of nondepressed women. Nondepressive disorders were
      associated with adverse family and stress factors for both groups of children.
      CONCLUSIONS: The results are consistent with a multiple risk factor model of
      depression transmission in high-risk families and suggest a pattern of reactivity
      to adverse conditions among children of depressed women. The results suggest that
      psychosocial factors may contribute to diagnoses in offspring of depressed women
      in community samples.

PMID- 15266195
TI  - School-based prevention of depressive symptoms in adolescents: a 6-month follow
      up.
AB  - OBJECTIVE: Depressive disorders in adolescents are a widespread problem with
      extensive psychosocial consequences. The authors designed a school-based program
      to prevent the increase in depressive symptoms. The authors expect the program to
      reduce dysfunctional automatic thoughts and improve social skills and thus
      prevent the increase in depressive symptoms. METHOD: The design includes a
      training group and a nontreatment control group with pre- and post-measurement
      and 3- and 6-month follow-up. The authors followed up 324 eighth graders in both
      groups. School classes were randomly assigned to one of the two groups. The
      prevention program, LISA-T, is based on cognitive-behavioral therapy concepts and
      targets of cognitive and social aspects. It comprises 10 meetings of 1.5 hours in
      a regular school setting. RESULTS: Increases in depressive symptoms in
      nondepressed adolescents in the training group were prevented over a 6-month
      period. Furthermore, adolescents with subsyndromal depression in the training
      group reported fewer symptoms, whereas depressive symptoms within the control
      group did not change. However, the groups did not differ with regard to social
      skills, frequency of negative automatic thoughts, and depressive symptoms before
      the prevention program. CONCLUSIONS: LISA-T is an effective school-based
      prevention program for eighth graders with minimal to mild depressive symptoms,
      but further research is needed.

PMID- 15266196
TI  - Cortisol and treatment effect in children with disruptive behavior disorders: a
      preliminary study.
AB  - OBJECTIVE: Basal cortisol and cortisol stress responsivity are valuable
      biological characteristics of children with disruptive behavior disorder (DBD).
      In this study, the predictive value of cortisol to outcome of intervention was
      investigated. METHOD: Basal cortisol levels and cortisol levels under stress were
      studied in 22 children with DBD before the start of a psychotherapeutic
      treatment. The disruptive behavior of the child was assessed before treatment and
      after cessation (9 months later). RESULTS: Children with DBD with relatively high
      and low basal cortisol levels differed in the severity of problem behavior at
      pretreatment, with the low basal cortisol group having more severe problems.
      During stress, children with DBD showed either increasing or decreasing cortisol
      values. Although these cortisol responsivity groups were similar in the severity
      of behavioral problems at pretreatment, the behavioral problems of the group with
      high cortisol stress responsivity were significantly lower after the intervention
      than the behavioral problems of the group with low cortisol stress responsivity.
      CONCLUSIONS: In children with DBD, the basal cortisol level was related to the
      severity of behavioral problems at pretreatment but not to the severity of
      behavioral problems after treatment. The cortisol response pattern during stress
      was related to treatment outcome.

PMID- 15266197
TI  - Physiological regulation and infantile anorexia: a pilot study.
AB  - OBJECTIVE: To examine whether infantile anorexia is associated with physiological
      dysregulation. METHOD: This study included eight toddlers with infantile anorexia
      and eight healthy eaters matched for age, race, socioeconomic status, and gender.
      Physiological measures of heart period and respiratory sinus arrhythmia were
      assessed across three different situations: mother-toddler interaction, toddler
      stranger interaction, and toddler left alone with a toy while mother and stranger
      talked to each other at the other side of the room. RESULTS: Across all three
      situations, toddlers with infantile anorexia showed significantly shorter heart
      periods (i.e., faster heart rates) than controls (p <.05). In addition, as social
      demand decreased from episode 2 to episode 3, control toddlers exhibited an
      increase in respiratory sinus arrhythmia, whereas toddlers with infantile
      anorexia showed a decrease in respiratory sinus arrhythmia (p <.001).
      CONCLUSIONS: Toddlers with infantile anorexia showed consistently shorter heart
      periods and were less adaptive in their physiological regulation than controls.
      Such physiological dysregulation may constitute a tendency for less optimal
      internal homeostatic regulation of feeding in toddlers with infantile anorexia.

PMID- 15266198
TI  - Looking for childhood schizophrenia: case series of false positives.
AB  - Extensive experience with the diagnosis of childhood-onset schizophrenia
      indicates a high rate of false positives. Most mislabeled patients have chronic
      disabling, affective, or behavioral disorders. The authors report the cases of
      three children who passed stringent initial childhood-onset schizophrenia
      "screens" but had no chronic psychotic disorder. For two, the European literature
      yielded more fitting diagnoses: psychosis not otherwise specified (e.g., reactive
      or psychogenic psychosis, paranoid schizophrenia), single episode in full
      remission (e.g., anxiety psychosis), and factitious disorder (DSM-IV 300.16).
      These cases illustrate that transient psychotic illnesses can be misdiagnosed as
      childhood-onset schizophrenia. Proper identification can prevent years of
      inappropriate therapies.

PMID- 15266199
TI  - Hallucinatory experiences in a community sample of Japanese children.
AB  - OBJECTIVE: Hallucinatory experiences in children are often thought to indicate
      serious psychopathology. However, they have also been reported in normally
      developing children and in association with temporary psychological reactions to
      acute stress. The aim of this study was to investigate the prevalence of
      hallucinatory experiences in a nonclinical population of children and to examine
      the relationship between the modality and content of hallucinations and
      psychopathology. METHOD: Seven hundred sixty-one Japanese children, 11 to 12
      years old, completed a battery of four measures: (1) a questionnaire about the
      type of hallucinatory experience, (2) the Children's Depression Inventory, (3)
      the State-Trait Anxiety Inventory for Children, and (4) the Adolescent
      Dissociative Experiences Scale. RESULTS: Approximately 21% of the subjects had
      experienced hallucinations. Subjects who had experienced hallucinations, in
      particular, hallucinations characterized by combined modalities, closely self
      related auditory content, or concrete visual content, had more significant
      psychopathology than did those who had never experienced hallucinations.
      CONCLUSIONS: Therapeutic intervention should be considered for children who
      experience hallucinations in association with depression, anxiety, or
      dissociation.

PMID- 15266200
TI  - AACAP 2001 research forum: challenges and recommendations regarding recruitment
      and retention of participants in research investigations.
AB  - OBJECTIVE: Clinical research depends on the participation of representative
      samples. At the 2001 Annual Meeting of the American Academy of Child and
      Adolescent Psychiatry, the Workgroup on Research conducted a research forum with
      the purpose of improving recruitment and retention of children and adolescents in
      research protocols. METHOD: An interdisciplinary group of participants focused on
      (1) consumers and families, (2) communities, (3) professionals and health care
      delivery systems, (4) regulatory bodies, and (5) alternative research designs.
      Obstacles and challenges were identified and solutions were discussed. RESULTS:
      Key recommendations include the following: Investigators must become involved
      with community stakeholders and more explicitly communicate with families about
      research procedures, risks, and benefits; budgets should include explicit items
      for case management and referrals to families who do not meet entry criteria; the
      culture of clinical settings must incorporate research conducted by clinicians;
      regulatory bodies must streamline and coordinate protocols and procedures;
      designs emphasizing flexible treatment strategies and adaptive treatments should
      be encouraged; and health care systems should consider changing incentives for
      research participation, including the radical notion that reimbursement be made
      in terms of improvement rather than service units. CONCLUSIONS: An integrated
      approach is recommended, requiring direct involvement of investigators in
      communities where research is to be conducted.

PMID- 15266201
TI  - AACAP 2002 research forum: placebo and alternatives to placebo in randomized
      controlled trials in pediatric psychopharmacology.
AB  - OBJECTIVE: The use of placebo in the pediatric age group has come under
      increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child
      and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a
      research forum. The purpose was to identify challenges and their solutions
      regarding the use of placebo in randomized controlled trials in pediatric
      psychopharmacology. METHOD: Workgroups focused on problems and solutions in five
      areas: ethics and human subjects, research design and statistics, partnering with
      consumers, U.S. Food and Drug Administration and pharmaceutical industry
      perspectives, and psychosocial treatments. RESULTS: In many but not all
      circumstances, inclusion of a placebo control is essential to meet the scientific
      goals of treatment outcome research. Innovative research designs; involvement of
      consumers in planning and implementing research; flexibility by industry,
      academia, the National Institutes of Health, and regulatory agencies acting in
      partnership; and concomitant use of evidence-based psychosocial services can and
      should assist in making placebo-controlled trials acceptable. CONCLUSIONS:
      Properly designed placebo-controlled trials remain necessary, ethical, and
      feasible.

PMID- 15266202
TI  - Introducing a structured interview into a clinical setting.

PMID- 15266203
TI  - Genetic testing: hope or hype?

PMID- 15266204
TI  - Alzheimer's disease and testing.

PMID- 15266205
TI  - Hereditary hemorrhagic telangiectasia: an overview of diagnosis and management in
      the molecular era for clinicians.
AB  - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a
      relatively common, underdiagnosed autosomal-dominant disorder of arteriovenous
      malformations and telangiectases. DNA testing for hereditary hemorrhagic
      telangiectasia has recently become available in North America, making
      presymptomatic screening available to relatives with a positive molecular
      diagnosis. This now enables practitioners to prevent catastrophic complications
      of undiagnosed pulmonary and CNS arteriovenous malformations and eliminates the
      need to radiographically screen all at-risk relatives shown to be unaffected by
      molecular testing. We review the clinical aspects of hereditary hemorrhagic
      telangiectasia, describe the indications, benefits, and limitations of molecular
      diagnostic testing for hereditary hemorrhagic telangiectasia, and provide a
      molecular genetics summary to facilitate genetic counseling before and after DNA
      testing for this complex disorder.

PMID- 15266206
TI  - Estimating risk curves for first-degree relatives of patients with Alzheimer's
      disease: the REVEAL study.
AB  - PURPOSE: The REVEAL study is a randomized, controlled study of the psychological
      and behavioral impact of APOE disclosure in a risk assessment protocol provided
      to first degree relatives of patients with Alzheimer's disease. The protocol
      presents risk information as cumulative incidence curves. This article describes
      how these curves were estimated. METHODS: Curves were calculated using Bayes'
      rule to compute the posterior survival curves incorporating APOE information.
      RESULTS: A combination of survival data from the MIRAGE study and gender- and age
      specific APOE odds ratios were used to create risk curves for males and females
      within each of the 6 APOE genotypes. CONCLUSION: Utilizing comparative genotype
      relative risk information and survival data from family studies, estimates of
      gender-, age-, and genotype-specific risk can be generated for use in a risk
      assessment research study that features genotype disclosure.

PMID- 15266207
TI  - Who seeks genetic susceptibility testing for Alzheimer's disease? Findings from a
      multisite, randomized clinical trial.
AB  - PURPOSE: Alzheimer's disease, for which one form of the apolipoprotein E (APOE)
      genotype is a risk factor, provides a paradigm in which to examine response to
      susceptibility testing for common, complex diseases. This study's main purposes
      were to estimate interest in such testing and to examine demographic predictors
      of study participation. METHODS: In this 3-site, randomized clinical trial (RCT),
      the intervention was a risk assessment program wherein genetic counselors
      educated adult children of AD patients about lifetime risk of disease based on
      their gender, family history, and APOE genotype. Two groups of participants were
      followed from initial contact to RCT enrollment: those who were systematically
      contacted through research registries, and those who were self-referred. RESULTS:
      Of 196 systematically contacted participants, 47, or 24%, progressed from initial
      contact to RCT enrollment. These participants were more likely to be below age 60
      (adjusted OR = 3.83, P < 0.01) and college educated (adjusted OR = 3.48, P <
      0.01). Of 179 self-referred participants, 115, or 64%, progressed from initial
      contact to RCT enrollment. Most self-referred participants had a college
      education and were female (79%). CONCLUSIONS: In the first RCT to examine genetic
      susceptibility testing for AD, uptake rates were sufficiently high to merit
      concern that future test demand may strain available education and counseling
      resources. Findings suggest that susceptibility testing for AD may be of
      particular interest to women, college educated persons, and persons below age 60.

PMID- 15266208
TI  - Genetic testing for alpha1-antitrypsin deficiency.
AB  - PURPOSE: The Alpha Coded Testing Study investigated the risks, benefits, and
      psychological impact of home genetic testing for alpha1-antitrypsin deficiency.
      METHODS: In the study, 996 adult individuals requested and returned a home
      administered, confidential, fingerstick blood test. RESULTS: Individuals highly
      rated the benefits of establishing a diagnosis (82%), helping family members
      (86%), and anticipating peace of mind (79%). 78% of 239 current smokers reported
      a high likelihood of smoking cessation if diagnosed with AATD. After testing,
      more than 60% indicated that they would share the results with family and
      physicians but < 30% would share results with insurance companies. CONCLUSIONS:
      Confidential home testing for genetic disorders requires a comprehensive program
      of participant support.

PMID- 15266209
TI  - A look at a Hispanic and African American population in an urban prenatal
      diagnostic center: referral reasons, amniocentesis acceptance, and abnormalities
      detected.
AB  - PURPOSE: To describe the Hispanic and African-American population referred to our
      inner city Los Angeles Prenatal Diagnostic Center. To evaluate trends in referral
      reasons, amniocentesis acceptance, and to assess the number and types of fetal
      abnormalities found from 1995 to 2001. METHODS: A retrospective study using the
      data from 3085 daily log entries on patients referred for prenatal counseling.
      The data included race, age, referral reason, amniocentesis decision and results,
      and fetal abnormalities. RESULTS: The population was 76% Hispanic and 22% African
      American. Most referrals were for advanced maternal age (42%) and maternal serum
      screening (28%). The overall amniocentesis acceptance rate was 52%; advanced
      maternal age amniocentesis acceptance rate was 46%, and maternal serum screen
      positive amniocentesis acceptance rate was significantly higher at 64%. There was
      a significant difference between the overall amniocentesis acceptance rate for
      Hispanics (48%) and African Americans (63%). There was also a significant
      downward trend in amniocentesis acceptance between 1995 (63%) and 2001 (39%).
      Amniocentesis acceptance was significantly greater among patients who were < 35
      years of age (65%) than those who were older (47%). An incidence of 7%
      abnormalities was detected by ultrasound and amniocentesis. CONCLUSIONS:
      Acceptance of amniocentesis in the Hispanic and African American population in
      our prenatal diagnostic center is significantly lower than what has previously
      been reported in the literature for Caucasians and reported in California
      statewide prenatal diagnostic center data for non-MS-AFP. There was a significant
      decline in amniocentesis acceptance from 1995 to 2001. Our incidence of fetal
      abnormalities was higher than reported in California statewide data.

PMID- 15266210
TI  - Genetic information leaflets: influencing attitudes towards genetic testing.
AB  - PURPOSE: This article explores how a "neutral" genetics information leaflet
      influenced people's attitudes to be more positive toward predictive genetic
      testing. This is of concern, given the desire within clinical genetics and
      population based testing to provide information that informs choice without
      directing toward, or against, testing. METHOD: Four studies are reported. The
      first two investigated presentation (glossy and colored vs. black and white), and
      method of reading (read only vs. read followed by probing questions). The second
      two investigated content, using "think aloud," "card sort," and delayed recall
      tasks. RESULTS: Those receiving a glossy leaflet expressed more positive
      attitudes and more interest in undergoing testing than those receiving a black
      and white leaflet, and those who were asked questions about what they had read
      were more positive about genetic testing than those who only read the leaflet.
      Recall one week later varied from 72% to 28%, depending on type of information.
      Information that described the advantages of genetic testing or discussed genes
      and genetic testing in relation to disease were well recalled and rated
      positively. Attitudes toward information ranged from 100% positive (e.g., what
      diseases genetic tests are available for) to 0% positive (e.g., the meaning of a
      positive result). CONCLUSION: These results show that quite small changes within
      a leaflet can change attitudes toward genetic testing. This is of concern, given
      the association between attitudes toward a behavior and undergoing that behavior.
      The form, method of presentation, and content of genetic information leaflets
      should be evaluated for impact on attitude and decisions before they are used
      clinically.

PMID- 15266211
TI  - Multimedia messages in genetics: design, development, and evaluation of a
      computer-based instructional resource for secondary school students in a Tay
      Sachs disease carrier screening program.
AB  - PURPOSE: Tay Sachs disease is a recessively inherited neurodegenerative disorder,
      for which carrier screening programs exist worldwide. Education for those offered
      a screening test is essential in facilitating informed decision-making. In
      Melbourne, Australia, we have designed, developed, and evaluated a computer-based
      instructional resource for use in the Tay Sachs disease carrier screening program
      for secondary school students attending Jewish schools. The resource entitled
      "Genetics in the Community: Tay Sachs disease" was designed on a platform of
      educational learning theory. METHODS: The development of the resource included
      formative evaluation using qualitative data analysis supported by descriptive
      quantitative data. The final resource was evaluated within the screening program
      and compared with the standard oral presentation using a questionnaire. Knowledge
      outcomes were measured both before and after either of the educational formats.
      RESULTS: Data from the formative evaluation were used to refine the content and
      functionality of the final resource. The questionnaire evaluation of 302 students
      over two years showed the multimedia resource to be equally effective as an oral
      educational presentation in facilitating participants' knowledge construction.
      CONCLUSION: The resource offers a large number of potential benefits, which are
      not limited to the Tay Sachs disease carrier screening program setting, such as
      delivery of a consistent educational message, short delivery time, and minimum
      financial and resource commitment. This article outlines the value of considering
      educational theory and describes the process of multimedia development providing
      a framework that may be of value when designing genetics multimedia resources in
      general.

PMID- 15266212
TI  - Omphalocele and gastroschisis: an 18-year review study.
AB  - PURPOSE: Using data from a single University Genetics Division practice, the
      authors sought to determine if gastroschisis is increasing in occurrence compared
      to omphalocele. Associated abnormalities were also examined. In addition,
      prenatal exposure to teratogens and other parameters were compared. METHODS: All
      fetal and infant cases of omphalocele and gastroschisis seen in the University of
      South Florida Division of Genetics between January 2, 1982 and December 31, 1999
      were retrieved through the database and analyzed through chart review. RESULTS:
      There were 127 cases of omphalocele and 121 cases of gastroschisis. Ninety-three
      of the 127 probands with omphalocele had karyotype determinations and 20% were
      abnormal; for gastroschisis, 37 had cytogenetic studies and none had chromosomal
      anomalies. Seventy-six percent of the probands with omphalocele had associated
      abnormalities; twenty-three percent of the probands with gastroschisis, none of
      which were syndromic, had associated anomalies. The prematurity rate for
      omphalocele was 42% and mortality was 22%; for gastroschisis, the figures were
      57% and 9%, respectively. There were no significant differences in teratogen
      exposure between the two groups. Familial cases of both defects occurred in < 4%,
      and the prevalence of dizygous twinning was increased in both groups. Mean
      maternal age was 21.8 years for the gastroschisis group, 27.2 years for the
      omphalocele group. CONCLUSIONS: In this study, the number of cases of omphalocele
      and gastroschisis were similar, compared to the expected 3:2 ratio, suggesting an
      increase in the occurrence of gastroschisis. Cases with omphalocele had more
      syndromic and nonsyndromic anomalies, more chromosomal anomalies, a higher
      mortality rate, and older mothers.

PMID- 15266213
TI  - APC I1307K and the E1317Q variants are not present in Chinese colorectal cancer
      patients.
AB  - PURPOSE: The APC I1307K and E1317Q variants predispose to colorectal adenomas and
      carcinomas in Caucasians, but data are lacking in Asians. METHODS AND RESULTS: We
      sequenced the APC gene from codons 1261 to 1409 and found none of 147 Chinese, 20
      Malay, and 11 Indian colorectal cancer patients in Singapore to carry the APC
      I1307K or E1317Q variants. CONCLUSION: These variants are rare in these Asian
      populations, and play little role in colorectal cancer causation in Chinese.

PMID- 15266214
TI  - What is a journal.

PMID- 15266216
TI  - Bacteremia in veterans administration nursing home patients.
AB  - The objective of this study was to identify differences between nursing home (NH)
      and nonnursing home (non-NH) patients with bacteremia regarding host risk
      factors, exposures, microbiology, and outcome. Between October 1995 and February
      1998, 134 episodes of true bacteremia were identified at the North Chicago
      Veterans Administration Medical Center (NCVAMC). Seventy-eight episodes of
      bacteremia occurred in NH patients who stayed for at least 3 months in the NH at
      the NCVAMC and developed bacteremia there or 48 hours after admission to the
      acute care hospital (ACH). Fifty-six episodes occurred in the non-NH patients who
      developed bacteremia in the community or 48 hours after admission to the ACH. NH
      patients were more likely to be older than 65 years (88% vs. 71%, P = 0.0334) and
      to have pressure sores (25% vs. 5%, P = 0.005), urinary incontinence (42% vs.
      27%, P = 0.0471), and mental illness (62% vs. 29%, P = 0.0001) than non-NH
      patients. Coagulase-negative Staphylococcus and Escherichia coli were the most
      common causes of bacteremia occurring as frequently in both groups. Methicillin
      resistant Staphylococcus aureus, Pseudomonas aeruginosa, and enterococcal
      bacteremia were comparable, whereas vancomycin-resistant enterococci, ceftazidime
      resistant E. coli, Klebsiella pneumoniae, and Enterobacter were rarely isolated.
      Twelve (15%) NH patients died within 2 weeks of acquiring bacteremia compared
      with 4 (7%) non-NH patients (P = 0.1176). For ACH-acquired cases, 20 NH patients
      were similar to 26 non-NH patients with regard to hospital stay; exposure to
      antibiotics, steroids, intensive care setting, surgery, tube feeding, and urinary
      and vascular catheters prior to bacteremia. Although NH and non-NH patients with
      bacteremia have different host characteristics, they have similar in-hospital
      exposures, distribution of infecting organisms, and outcome.

PMID- 15266215
TI  - Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal
      antiinflammatory agents and placebo on cardiovascular thrombotic events in
      patients with arthritis.
AB  - There have been concerns that the risk of cardiovascular thrombotic events may be
      higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective
      nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event
      data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000
      patients with osteoarthritis and rheumatoid arthritis treated with this agent in
      randomized clinical trials. The incidence of cardiovascular thrombotic events
      (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was
      determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID
      (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo
      data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were
      6-52 weeks in duration. The incidence rates of events were determined in all
      patients (n = 7934) and in users of low-dose (< or =325 mg daily) aspirin (n =
      1051) and nonusers of aspirin (n = 6883). Crude and exposure-adjusted incidences
      of thrombotic events were similar for valdecoxib, NSAIDs, and placebo. The risk
      of serious thrombotic events was also similar for each valdecoxib dose.
      Thrombotic risk was consistently higher for users of aspirin users than nonusers
      of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs.
      0.5%). The rates of events in users of aspirin were similar for all 3 treatment
      groups and across valdecoxib doses. Short- and intermediate-term treatment with
      therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily)
      valdecoxib doses was not associated with an increased incidence of thrombotic
      events relative to nonselective NSAIDs or placebo in osteoarthritis and
      rheumatoid arthritis patients in controlled clinical trials.

PMID- 15266217
TI  - Ingestion of caustic substances by adults.
AB  - Caustic products are responsible for the most serious cases of poisoning, which
      are always emergency cases. In this paper, we review demographic features and
      endoscopic results of the patients admitted to a university emergency department
      with a history of caustic substance ingestion between January 2000 and June 2003.
      Thirty-seven patients were included in this study. Twenty-one of the patients
      were female and 16 were male. The mean age of the patients was 30.9 +/- 14.7
      years. The agents included sodium hypochlorite in 24 patients and hydrochloric
      acid in 13 patients. All the patients ingested these agents orally. The mean
      interval time of admission to emergency department after ingestion of caustic
      agent was 5.4 +/- 5.6 hours. Endoscopy was attempted in 37 patients. Endoscopic
      results were as follows: grade 0 in 8 (21.6%) patients, grade 1 in 17 (45.9%)
      patients, grade 2a in 5 (13.5%) patients, and grade 2b in 7 (18.9%) patients. We
      believe that early signs and symptoms after caustic substance ingestion are not
      consistent with the extent of damage, and endoscopy is the only reliable method
      to assess injury. It is important that efforts should be made to educate the
      public about the dangers of caustic substances so that their threat may be
      diminished.

PMID- 15266218
TI  - In vitro interaction of the HIV protease inhibitor ritonavir with herbal
      constituents: changes in P-gp and CYP3A4 activity.
AB  - The purpose of this study was to evaluate in vitro interactions of commercially
      obtained pure herbal constituents with p-glycoprotein P-gp and cytochrome P-450
      3A4 (CYP3A4) activities, which can further modulate the transcellular transport
      and metabolism kinetics of orally administered drugs. Caco-2 cells grown in the
      presence of 0.25 micromol/L 1alpha,25-dihydroxy vitamin D3 and multidrug
      resistant 1 (MDR1) transfected MDCK cells were used as models to evaluate the
      effect of purified herbal constituents (quercetin, hypericin, hyperforin from St.
      John's wort, kaempferol from ginseng, silibinin from milk thistle, and allicin
      from garlic) on P-gp-mediated efflux of the human immunodeficiency virus (HIV)
      protease inhibitor ritonavir. In addition, the inhibitory effect of these
      constituents on CYP3A4-mediated metabolism was determined by using cortisol as a
      model compound. Silibinin and hyperforin did not significantly alter cellular
      uptake of H-ritonavir in Caco-2 cells. A similar result was also observed for
      silibinin when tested in MDR1-MDCK cells. Quercetin, hypericin, and kaempferol
      exhibited a remarkable inhibition of P-gp-mediated efflux of ritonavir by
      increasing its cellular uptake in these models. These values were also comparable
      with the inhibitory effect of quinidine in Caco-2 cells, a well-known inhibitor
      of P-gp, on ritonavir efflux from Caco-2 cells. Allicin exhibited a concentration
      dependent inhibition of ritonavir efflux when tested on MDR1-MDCK cells. There
      was a significant decrease in the Apical to Basal/Basal to Apical (AP-BL/BL-AP)
      transport ratio of ritonavir in presence of hypericin, kaempferol, and quercetin.
      These herbal constituents inhibited the CYP3A4 activity when tested with the
      Vivid CYP3A4 assay kit, whereas silibinin did not alter cortisol metabolism.
      Hypericin showed a significant inhibition in reduced nicotinamide adenine
      dinucleotide phosphate (NADPH)-dependent metabolism of cortisol with 64.6% of
      intact drug at the end of a 1-hour study. Similarly, kaempferol and quercetin
      also caused substantial inhibition of cortisol metabolism with 89.7% and 90.1% of
      intact cortisol, respectively, compared with 45.9% in the control. Prolonged
      exposure of quercetin resulted in significant increase of mRNA expression of both
      MDR1 and CYP3A4 levels in Caco-2 cells. However, hyperforin caused upregulation
      of CYP3A4 and downregulation of MDR1, whereas the effect of silibinin and
      kaempferol remained inconclusive on these gene expressions. Hypericin,
      kaempferol, quercetin, and allicin inhibit the efflux and CYP3A4-mediated
      metabolism of xenobiotics in vitro. Hence, this study warns against the use of
      herbal constituents along with prescribed HIV protease inhibitors that are
      substrates for P-gp and/or CYP3A4.

PMID- 15266219
TI  - Benefits and risks of granisetron versus ramosetron for nausea and vomiting after
      breast surgery: a randomized, double-blinded, placebo-controlled trial.
AB  - Women undergoing general anesthesia for breast surgery are at particular risk of
      postoperative nausea and vomiting. In a randomized, double-blinded, placebo
      controlled trial, 90 patients scheduled for breast surgery, aged 33-63 years,
      received intravenously placebo, 3 mg granisetron, or 0.3 mg ramosetron (n = 30 of
      each) at the end of surgical procedure. A standard general anesthetic technique
      and postoperative analgesia were used. Emetic episodes and safety assessment were
      performed during 0-24 hours and 24-48 hours after anesthesia. The rate of
      patients experiencing emetic symptoms (nausea, retching, vomiting) 0-24 hours
      after anesthesia was 17% with granisetron (P = 0.013) and 10% with ramosetron (P
      = 0.002) compared with placebo (47%); the corresponding rate 24-48 hours after
      anesthesia was 27% (P = 0.032) and 7% (P = 0.001), compared with placebo (53%).
      In the 24-48 hours after anesthesia, there were fewer emetic episodes in patients
      who had received ramosetron than in those who had received granisetron (P =
      0.039). The severity of nausea was less in patients receiving ramosetron than in
      those receiving granisetron (P = 0.044). Zero to 24 hours after anesthesia, no
      difference in the rate of patients having emetic symptoms and the severity of
      nausea was observed between the granisetron and ramosetron groups. The most
      common reported adverse events were headache and dizziness, and there were no
      difference in the incidence of adverse events due to the study drug among the 3
      groups. In conclusion, prophylactic therapy with ramosetron is more effective
      than that with granisetron for the long-term prevention of postoperative nausea
      and vomiting in women undergoing general anesthesia for breast surgery.

PMID- 15266220
TI  - Some plasma and saliva pharmacokinetics parameters of rifampicin in the presence
      of pefloxacin.
AB  - The effect of pefloxacin on the pharmacokinetics parameters of rifampicin in
      humans was investigated using plasma and saliva concentrations. Five healthy
      volunteers (4 male and 1 female), ages 20-35 years, each received 600 mg
      rifampicin alone, and after a 1-week drug washout period, 600 mg rifampicin plus
      500 mg pefloxacin was administered with 350 mL of water. Plasma and saliva
      concentrations of rifampicin were measured at 7 different time intervals and
      different pharmacokinetics parameters calculated. Pefloxacin coadministered with
      rifampicin reduced plasma and saliva elimination half-life, peak plasma
      concentration, area under the concentration time curve, volume of distribution,
      minimum absorption time, absorption rate constant, and absorption half-life
      showed a significant increase (P < 0.05). Time to reach peak plasma concentration
      was not affected with or without pefloxacin. Pefloxacin increases bioavailability
      of rifampicin and hence extends its detection in the body as demonstrated by
      rifampicin being estimated at 24 hours when coadministered with pefloxacin,
      whereas at 24 hours, it was completely absent when administered alone.

PMID- 15266221
TI  - Chemotherapy for prostate cancer: finally an advance!
AB  - Patients with metastatic prostate cancer can be treated with androgen deprivation
      strategies; however, most patients will eventually develop androgen-independent
      prostate cancer (AIPC). Until recently, chemotherapy has been shown to palliate
      symptoms of disease but not improve survival. Now 2 large phase 3 trials have
      demonstrated an overall survival advantage for docetaxel-based regimens compared
      with the best standard of care. This firmly cements docetaxel-based therapies as
      the standard of care for patients with metastatic androgen-independent disease.
      In addition, this foundation provides a platform for the translation of novel
      agents into new combination cancer therapies. In this paper, we not only review
      standard treatment options available for AIPC including the recently completed
      docetaxel trials, but also present some of the promising new drug combinations of
      currently available drugs.

PMID- 15266222
TI  - Limitations in the clinical usefulness of single-dose pharmacokinetic studies of
      drugs and a bayesian approach for the estimation of kinetic parameters.
AB  - This review presents several clinical examples indicating that physiological
      changes in the body dependent and/or independent of developmental age, genetic
      polymorphisms, different disease states, acute and/or chronic inflammations, and
      physicochemical properties of drugs as well as some environmental factors, such
      as viral infections, may exert a significant effect on the first-time assessment
      of kinetic parameters of drug absorption, disposition, metabolism, and excretion
      after a single-dose administration in children and adults. The available
      pharmacokinetic data in the literature suggest that one must be cautious in
      interpretation and practical use of pharmacokinetic variables derived from either
      single-dose studies or bayesian methods, especially in a pediatric population.

PMID- 15266223
TI  - Therapeutics of platelet glycoprotein IIb/IIIa receptor antagonism.
AB  - The integrin glycoprotein IIb/IIIa receptor is the final common pathway to
      platelet aggregation. Administration of glycoprotein IIb/IIIa receptor
      antagonists reduces acute ischemic complications following plaque fissuring or
      rupture. Research on this subject was initially limited to patients undergoing
      percutaneous coronary intervention. Further studies evaluating the role of
      glycoprotein IIb/IIIa receptor antagonists in patients with non-ST segment
      elevation acute coronary syndrome have shown benefit of these drugs in reducing
      adverse cardiac events and death. Intravenous glycoprotein IIb/IIIa receptor
      inhibitors (abciximab, tirofiban, and eptifibatide) given in combination with
      traditional regimens are superior to placebo in management of non-ST elevation
      acute myocardial infarction. Oral glycoprotein IIb/IIIa receptor inhibitors
      (orbofiban, sibrafiban, and xemilofiban) are not effective in reducing ischemic
      events when used on a long-term basis after acute coronary syndrome.
      Pharmacokinetics, efficacy, and safety of glycoprotein IIb/IIIa receptor
      antagonists are elaborated.

PMID- 15266224
TI  - The role of C-peptide levels in screening for latent autoimmune diabetes in
      adults.
AB  - Early detection of latent autoimmune diabetes in adults (LADA) is important in
      that the earlier insulin therapy is initiated, the greater the preservation of
      pancreatic beta cells. This study assessed whether a random C-peptide level is an
      effective screening test for LADA. Random C-peptide levels were measured in 39
      subjects with LADA and 39 subjects with type 2 diabetes who were matched for age,
      race, gender, and duration of diabetes. LADA was definitively diagnosed by the
      presence of antiglutamic acid decarboxylase antibodies. The mean C-peptide level
      in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with
      type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal
      range, and all subjects with type 2 diabetes had a C-peptide level within or
      above the normal range. LADA can be ruled out in adult-onset diabetes by the
      presence of elevated C-peptide. The more expensive testing for anti-GAD
      antibodies to definitively diagnose LADA should be reserved for patients who on
      screening have a low or normal random C-peptide level.

PMID- 15266225
TI  - Emerging technologies in transdermal therapeutics.
AB  - Until very recently, the only drugs that could permeate transdermally were those
      possessing a very narrow and specific combination of physicochemical properties.
      However, rapid advances in bioengineering have led to the emergence of various
      new "active" enhancement technologies designed to transiently circumvent the
      barrier function of the stratum corneum. These novel systems, using
      iontophoresis, sonophoresis, electroporation, or microneedle arrays, will greatly
      expand the range of drugs that can be delivered transdermally. Crucially, the
      delivery of macromolecules will become possible and the transdermal flux of other
      molecules could be enhanced by several orders of magnitude. This article
      sequentially reviews the basis of each of the new enhancement techniques and
      discusses how these emerging technologies will influence transdermal therapy in
      the coming years.

PMID- 15266226
TI  - Clinical trials: Renewed attention to the interpretation of the P values--review.
AB  - The P values tell us the chance of making a type I error of finding a difference
      where there is none. In the 1970s, exact P values were laborious to calculate and
      were generally approximated from statistical tables, in the form of P < 0.01 or
      0.05 < P < 0.10, etc. In the past decades with the advent of computers, it became
      easy to calculate exact P values such as 0.84 or 0.007. The cut-off P values have
      not been completely abandoned, but broader attention is given to the
      interpretation of the exact P values. This article reviews standard and renewed
      interpretations of P values. (1) Standard interpretation of cut-off P values such
      as P < 0.05: The null hypothesis of no difference can be rejected on the
      limitations/assumptions that we have up to a 5% chance of a type I error of
      finding a difference where there is none, we have 50% chance of a type II error
      of finding no difference where there is one, the data are normally distributed,
      they follow exactly the same distribution as that of the population from which
      the sample was taken. (2) A common misunderstanding of the P value: It is
      actually the chance that the null hypothesis is true and consequently that a P >
      0.05 indicates a significant similarity in the data. P > 0.05 may indeed indicate
      similarity. However, a study sample too small or study design inadequate to
      detect the difference must be considered. (3) Renewed interpretations of the P
      values: Exact P values enable more refined conclusions from the research than cut
      off levels. Instead of concluding significantly yes/no, we are able to consider
      levels of probabilities from very likely to be true to very likely to be untrue.
      Very large P values are not compatible with a normal gaussian frequency
      distribution; very small P values do not completely confirm prior expectations.
      They must be scrutinized and may have been inadequately improved.

PMID- 15266227
TI  - Acute reversible heart failure with highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy is effective in the management of AIDS. It
      has improved the prognosis of human immunodeficiency virus (HIV) infection.
      However, with increased survival, adverse effects from medications used in HIV
      treatment have become more apparent. Cardiac complications from HIV infection
      include arrhythmias, heart failure, and coronary artery disease. Heart failure in
      HIV disease may be related to the virus itself or to noninfectious reasons. The
      association of HIV medications with heart failure is controversial as patients
      with HIV disease often have multiple risk factors for developing heart failure.
      We present a case of acute onset heart failure in a patient with HIV, coronary
      artery disease, and hypertension who was recently started on antiretroviral
      therapy. There was complete resolution of heart failure after cessation of HIV
      medications. This case highlights the need to consider HIV medications as a cause
      of deterioration in cardiac function, even in the presence of other well
      established risk factors for heart failure.

PMID- 15266228
TI  - A survey on current attitude of practicing physicians upon usage of antimicrobial
      agents in southern part of India.
AB  - CONTEXT: Antimicrobial resistance is a serious public health concern worldwide.
      Inappropriate prescribing, including the wrong drug, incorrect dose/duration, and
      poor compliance, contributes to it. OBJECTIVE: To identify factors determining
      the attitudes and practices of prescribers regarding antibiotic usage and to
      suggest measures that contain antibiotic resistance. DESIGN AND SETTING: With a
      convenient sample, general practitioners and specialists of both sexes from 5
      districts of Tamilnadu state, India, were approached for the study. A slightly
      modified, self-administered, anonymous questionnaire of the Alliance for the
      Prudent Use of Antibiotics was used. The deciding factors to prescribe an
      antibiotic and the reasons for the attitude to prescribe a broad-spectrum
      antibiotic were elicited. RESULTS: Out of the 285 participants 120, 110, and 47
      practiced at city, semiurban, and rural areas, respectively. The responses were
      graded with a total possible score of 150. There was no significant difference
      between men and women or between specialist and nonspecialists in scores. The
      majority believed that antibiotics are overprescribed. Purulent discharge (65%),
      antibiotic-resistance concerns (48%), fever (40%), and patient satisfaction (29%)
      were the strong influences to prescribe an antibiotic. Similar reasons were cited
      for the belief of prescribing a broad-spectrum antibiotic. The 3 most commonly
      prescribed antimicrobials were amoxicillin (21%), ciprofloxacin (18%), and co
      trimoxazole (11%). About 42% used an antibiogram only to the extent of less than
      10%. CONCLUSION: Patient requests/expectations, patient satisfaction, purulent
      discharge, and fever strongly pressurized practitioners to prescribe antibiotics.
      Patient and time pressures, diagnostic and treatment uncertainties, and the poor
      utilization and/or ill-affordable antibiogram facility all point to an urgent,
      multidimensional approach to contain antibiotic resistance.

PMID- 15266229
TI  - Perceptions of girls and ADHD: results from a national survey.
AB  - OBJECTIVE: The purpose of this survey is to explore perceived gender differences
      in attention-deficit/hyperactivity disorder (ADHD). METHODS: Online Harris
      Interactive interviews were conducted with 1797 adults (general public), 541
      parents of children with ADHD, 550 teachers, and 346 children aged 12 to 17 years
      with ADHD. Responses were examined to determine perceptions of ADHD. RESULTS:
      Most of the general public (58%) and teachers (82%) think ADHD is more prevalent
      in boys. The general public and teachers think boys with ADHD are more likely
      than girls to have behavioral problems (public: 52% vs 26%; teachers: 36% vs 18%,
      respectively), while girls with ADHD are thought to have less noticeable problems
      than boys, such as being inattentive (public: 19% vs 11%; teachers: 29% vs 10%,
      respectively) or feeling depressed (public: 16% vs 1%; teachers: 12% vs 0.0%,
      respectively). Four out of 10 teachers report more difficulty in recognizing ADHD
      symptoms in girls. An overwhelming majority of teachers (85%) and more than half
      of the public (57%) and parents (54%) think girls with ADHD are more likely to
      remain undiagnosed. ADHD was reported to have a negative effect on self-esteem,
      more so in girls. Girls who were taking medication for their ADHD were nearly 3
      times more likely to report antidepressant treatment prior to their ADHD
      diagnosis. Girls were more likely to feel it was "very difficult" to focus on
      schoolwork and get along with parents. CONCLUSIONS: Survey responses suggest that
      gender has important implications in the diagnosis and treatment of ADHD.
      Responses by ADHD patients demonstrate gender-specific differences in the
      personal experience of the condition. Future prospective clinical trials are
      warranted to clarify the unique needs and characteristics of girls with ADHD.

PMID- 15266230
TI  - Physiotherapy in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads
      to progressive joint damage, disability, deterioration in quality of life, and
      shortened life expectancy. Even mild inflammation may result in irreversible
      damage and permanent disability. The clinical course according to symptoms may be
      either intermittent or progressive in patients with RA. In most patients, the
      clinical course is progressive, and structural damage develops in the first 2
      years. The aim of RA management is to achieve pain relief and prevent joint
      damage and functional loss. Physiotherapy and rehabilitation applications
      significantly augment medical therapy by improving the management of RA and
      reducing handicaps in daily living for patients with RA. In this review, the
      application of physiotherapy modalities is examined, including the use of
      cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation
      treatment techniques for patients with RA such as joint protection strategies,
      massage, exercise, and patient education are also presented.

PMID- 15266231
TI  - Recycling expensive medication: why not?
AB  - New (and proposed) advances in packaging, preserving, labeling, and verifying
      product integrity of individual tablets and capsules may allow for the recycling
      of certain expensive medicines. Previously sold, but unused, medication, if
      brought back to special pharmacies for resale or donation, may provide a low-cost
      source of patent-protected medicines. Benefits of such a program go beyond simply
      providing affordable medication to the poor. This article suggests that medicine
      recycling may be a possibility (especially if manufacturers are mandated to
      blister-package and bar-code individual tablets and capsules). This early
      discussion of medication recycling identifies relevant issues, such as: need,
      rationale, existing programs, available supplies, expiration dates, new
      technology for ensuring safety and potency, environmental impact, public health
      benefits, program focus, program structure, and liability.

PMID- 15266232
TI  - Very high prevalence of enterobiasis among the hilltribal children in rural
      district "Mae Suk," Thailand.

PMID- 15266233
TI  - Nail-patella syndrome in Saudi Arabia with new features and surgical procedures:
      the first described study.
AB  - The purpose of this study was to reveal the occurrence of nail-patella syndrome
      (NPS) in Saudi Arabia together with the detection of abnormal attachment of
      lateral meniscus in the left knee and new surgical procedures applied to the
      right and left knee, reported for the first time in this study. This was a case
      study of a 23-year-old young man presenting with bilateral knee pain, giving way
      and locking since the age of 15 years. Clinically, most of the NPS features were
      noted, including ocular problems. The complex features affected both knees,
      especially the previous attempted surgeries for recurrent dislocation of
      patellae. Deficient ligaments were reconstructed using the Leeds-Keio ligament,
      starting with the right knee and continuing with the left knee 6 months later.
      Early and late follow-up showed favorable outcome of surgery revealed as
      independent ambulation and stable right and left knees. In conclusion, NPS,
      although rare, presents a complex problem and unexpected surgical outcome, and we
      recommend this procedure with close follow-up.

PMID- 15266234
TI  - Overview of hymenolepis diminuta infection among Thai patients.
AB  - CONTEXT: Hymenolepis diminuta infection is a very rare cestode infection. Until
      present, fewer than 500 cases have been observed worldwide. OBJECTIVE: The author
      performed a literature review on the reports of H diminuta in Thailand in order
      to summarize the characteristics of this infection among Thai patients. DESIGN:
      This study was designed as a descriptive retrospective study. A literature review
      of the papers concerning H diminuta infections in Thailand was performed.
      RESULTS: According to this study, there have been at least 6 reports in the
      literature of 10 individual cases of H diminuta infection, of which 1 case was
      lethal. Of 4 cases that documented patients' age, the ages ranged from 20 months
      to 55 years. Of 5 cases that documented patients' sex, 3 were males and 2 were
      females. Most (9/10) were asymptomatic; however, there was 1 inpatient case,
      concomitant with metastatic cholangiocarcinoma. Antiparasitic drugs were
      prescribed in 3 cases: niclosamide in 2 cases and praziquantel in 1 case. The 2
      patients receiving niclosamide passed the parasites after treatment. CONCLUSION:
      In conclusion, the H diminuta infection is a rare cestode infection that is
      sporadically reported in Thailand. The diagnosis of H diminuta infection is
      usually by accident during a field survey. The prognosis outcome is usually good,
      and the treatment does not appear to affect outcome, as there is good survival
      without treatment.

PMID- 15266235
TI  - The two-headed swan.
AB  - Pulmonary artery catheterization is a frequent procedure for hemodynamic
      monitoring in critically ill patients or high-risk surgical patients. Mechanical
      and infectious complications are recognized, though catheter dysfunction and
      malposition are more frequent and often require clinical intervention. We present
      the case of a Swan-Ganz catheter with the appearance of a mechanical fracture at
      the distal end, which required clinical and radiographic investigation to
      determine the nature of the aberrancy. The evaluation of a malfunctioning
      pulmonary artery catheter (PAC) is a frequent occurrence in the intensive care
      unit and requires careful clinical consideration and radiographic examination.

PMID- 15266236
TI  - Pathway to independence: physical therapy for patients with rheumatoid arthritis.

PMID- 15266238
TI  - The medical and surgical management of short bowel syndrome.

PMID- 15266239
TI  - GERD in the pediatric patient: management considerations.

PMID- 15266240
TI  - Cases in pediatric gastroenterology from The Children's Hospital of Philadelphia.
      A 5-year-old girl with massive hepatosplenomegaly, fever, and rash.

PMID- 15266242
TI  - Grand rounds in gastroenterology from Baylor College of Medicine. A 42-year-old
      cushingoid man with a bleeding duodenal ulcer.

PMID- 15266241
TI  - Gastrointestinal complications of obesity surgery.

PMID- 15266243
TI  - Underreporting of minor transfusion reactions in cancer patients.
AB  - BACKGROUND: Minor adverse reactions following transfusion of blood components to
      cancer patients are not uncommon. Reporting these minor reactions to the
      transfusion service needs a careful evaluation. The objectives of this study were
      to closely monitor the transfusion reactions that occurred and had not been
      reported to the transfusion service and to evaluate the process by which the
      medical and nursing staff recognized and managed these reactions. METHODS: We
      prepared a questionnaire with the nursing staff of a selected inpatient unit that
      addressed important questions, such as signs and symptoms during the transfusion,
      premedications given, process for physician notification, recommended action, and
      blood component implicated. Charts of the patients were reviewed, and the process
      was monitored for a 6-month period. RESULTS: A total of 58 cases were completed
      and analyzed. Platelet concentrates were transfused in 43 cases (74.1%), packed
      red blood cells in 9 cases (15.6%), and fresh frozen plasma in 6 cases (10.3%).
      Minor adverse reactions that were documented included chills in 11 cases (19.0%),
      low-grade fever in 11 cases (19.0%), hives and itching in 24 cases (41.4%),
      nausea and vomiting in 1 case (1.7%), and headaches and nonspecific mild pains in
      11 cases (19.0%). Transfusions had been resumed in 27 cases (46.6%) and stopped
      completely in 13 cases (22.4%). Twenty-seven of 58 (46.6%) were first-time
      events. CONCLUSION: We conclude that underreporting of minor transfusion
      reactions, such as a febrile nonhemolytic transfusion reaction and allergic
      reactions, exists. To ensure safety to our cancer patients who are transfusion
      dependent, we suggest that careful evaluation of any suspected transfusion
      reaction event should be referred to the transfusion medicine physicians who will
      evaluate each case and discuss it with the attending physician. This process will
      prevent detrimental, acute transfusion reactions.

PMID- 15266245
TI  - Conference report--at the forefront of cancer research: clinical results
      highlights of the annual meeting of the 95th American Association for Cancer
      Research, March 27-31, 2004; Orlando, Florida.

PMID- 15266244
TI  - Conference report--at the forefront of cancer research: preclinical data
      highlights of annual meeting of the 95th American Association for Cancer
      Research; March 27-31, 2004; Orlando, Florida.

PMID- 15266246
TI  - Conference report--cancer research 2004--top of the class March 27-March 31,
      2004; Orlando, Florida.

PMID- 15266247
TI  - Conference report--genomics: the promise of SNPs and bats highlights of the ABRF
      2004--integrating technologies in proteomics and genomics; February 28-March 2,
      2004; Portland, Oregon.

PMID- 15266248
TI  - Conference report--structural genomics: parsing the architecture of proteins
      highlights of the ABRF 2004--integrating technologies in proteomics and genomics,
      February 28-March 2, 2004; Portland, Oregon.

PMID- 15266251
TI  - Conference report--protein kinase inhibitors in cancer treatment: mixing and
      matching? Highlights of the keystone symposium on protein kinases and cancer;
      February 24-29, 2004; Lake Tahoe, California.

PMID- 15266250
TI  - Conference report--protein microarrays in cancer and autoimmunity: tiny spots
      light up highlights of the ABRF 2004--integrating technologies in proteomics and
      genomics; February 28-March 2, 2004; Portland, Oregon.

PMID- 15266252
TI  - Psychopharmacology in the New York Times.

PMID- 15266254
TI  - All the things they taught us that were wrong.

PMID- 15266255
TI  - International Consensus Group on Bipolar I Depression Treatment guidelines:
      synopsis and discussion.

PMID- 15266253
TI  - Cognitive effects of olanzapine treatment in schizophrenia.
AB  - Improvement in some but not all domains of cognition during treatment with the
      atypical antipsychotic drugs clozapine, quetiapine, olanzapine, and risperidone
      has been reported in some but not all studies. It has been recently suggested
      that these reports are an artifact, related to lessening of the impairment due to
      typical neuroleptic drugs and anticholinergic agents. The purpose of this study
      was to further test the hypothesis that olanzapine, an atypical antipsychotic
      drug reported to have anticholinergic properties, improves cognition in patients
      with schizophrenia, including domains of cognition related closely to work and
      social function (ie, verbal learning and memory) and that this improvement is
      independent of improvement in psychopathology. Thirty-four patients with
      schizophrenia who were partial responders to typical antipsychotic drug treatment
      were evaluated with a comprehensive neurocognitive battery, including measures of
      executive functioning; verbal and visual learning and memory; working memory;
      immediate, selective, and sustained attention; perceptual/motor processing; and
      motor skills prior to and following treatment with olanzapine for 6 weeks. The
      Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology in
      patients treated with typical antipsychotic drugs. Subjects were switched to
      olanzapine (average dose 13.4 mg, range 5-20 mg) and reassessed following 6 weeks
      and 6 months of treatment. Significant improvement was noted in 9 of 19 cognitive
      tests, including measures of selective attention, verbal learning and memory, and
      verbal fluency. No cognitive test was worsened by olanzapine treatment.
      Improvements in the BPRS Total and Positive Symptom Subscale scores were noted.
      Improvements in verbal learning and memory, sustained attention, and psychomotor
      tracking were independent of improvement in psychopathology. These data suggest
      that olanzapine improved some but not all cognitive deficits in schizophrenia,
      including verbal memory, a cognitive domain impaired by anticholinergic drugs.
      The basis for the improvement in cognitive scores, which should lead to
      improvement in role functioning if real, is discussed.

PMID- 15266256
TI  - Talking points about antidepressants and suicide.

PMID- 15266257
TI  - K65R-associated virologic failure in HIV-infected patients receiving tenofovir
      containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens.
AB  - High rates of early virologic failure associated with the emergence of the K65R
      mutation in HIV-1 reverse transcriptase (RT) have been reported among HIV
      infected patients who received novel, tenofovir-containing, triple
      nucleoside/nucleotide reverse transcriptase inhibitor (NRTI/NtRTI) regimens as
      their initial therapy. This review surveys the findings of prospective and
      retrospective studies in this regard, examines the significance of the K65R
      mutation and other factors associated with reports of early virologic failure
      among patients receiving tenofovir-containing NRTI/NtRTI regimens, and discusses
      clinical approaches to preventing and managing HIV drug resistance and treatment
      failure associated with the K65R mutation.

PMID- 15266258
TI  - Intensive glucose control in the ICU: an expert interview with James S. Krinsley,
      MD by Antonios Liolios.

PMID- 15266259
TI  - Enriching medicine by raising the bar and keeping it high: a letter to Dr.
      Keppler and Dr. Lundberg.

PMID- 15266261
TI  - A clarification of critical appraisal, evidence, and education.

PMID- 15266260
TI  - Alternative medicine outside the ivory towers.

PMID- 15266262
TI  - Physician leadership and integrity.

PMID- 15266264
TI  - Staffing the free medical clinics.

PMID- 15266266
TI  - Webcasting concurrent text-audio-video messages.

PMID- 15266265
TI  - The American president and electronic medical records.

PMID- 15266267
TI  - Editorial on "error in medicine and patient safety".

PMID- 15266270
TI  - Helmet-related, external compression headache among police officers in Rio de
      Janeiro.

PMID- 15266272
TI  - The painful life of Cole Porter.

PMID- 15266273
TI  - Clinical cases in neurology from Johns Hopkins. Case 6: when is a headache not
      just a headache?

PMID- 15266271
TI  - The therapeutic potential of melatonin: a review of the science.

PMID- 15266274
TI  - Case 5: altered mental status and fever after resection of glioblastoma
      multiforme.

PMID- 15266275
TI  - Case files from the University of Chicago's Sleep Disorders Center. Case 1: a
      gigantic fatigue.

PMID- 15266276
TI  - Treating female infertility and improving IVF pregnancy rates with a manual
      physical therapy technique.
AB  - CONTEXT: Infertility and pregnancy. OBJECTIVE: To assess the effectiveness of
      site-specific manual soft tissue therapy in (1) facilitating natural fertility
      and (2) improving in vitro fertilization (IVF) pregnancy rates in women with
      histories indicating abdominopelvic adhesion formation. DESIGN AND INTERVENTION:
      Pursuant to 2 promising pilot studies, 53 infertile, premenopausal patients
      received a 10- to 20-hour series of site-specific manual physical therapy
      treatments. Seventeen patients hoped to achieve a natural pregnancy; 36 planned
      to undergo IVF within 15 months. The primary criteria for inclusion in the
      studies were the inability to conceive following a minimum of 12 months of
      unprotected intercourse and suspected or confirmed pelvic adhesions due to
      abdominal and/or pelvic surgery, infectious or inflammatory disease (eg,
      endometriosis, PID), or trauma. Treatments were specifically designed to address
      biomechanical dysfunctions of the pelvis, sacrum, and coccyx and restricted soft
      tissue and visceral mobility due to adhesions or microadhesions affecting the
      reproductive organs and adjacent structures. MAIN OUTCOME MEASURES: (1) Natural
      fertility group: pregnancy within 1 year of therapy and subsequent full-term
      delivery; (2) Pre-IVF group: pregnancy (via transfer of fresh embryos from
      nondonor eggs) within 15 months of the last manual treatment date. RESULTS:
      Natural fertility group: Of the 14 patients available for follow-up (ages 25 to
      44; mean, 33.5 years), 10 (71.4%) became pregnant within 1 year, and 9 (64.3%)
      reported full-term deliveries. Three of the 9 women who delivered reported a
      subsequent pregnancy, suggesting that the treatment protocol might have lasting
      effects. Two women have had a second live birth delivery; and the third is still
      pregnant. Pre-IVF group: Of the 25 patients available for follow-up (ages 28 to
      44; mean, 36 years), clinical pregnancies were documented in 22 of 33 embryo
      transfers vs the US Centers for Disease Control and Prevention (CDC) 2001 age
      adjusted expected number of 12.7 (P < .001). The estimated odds ratio for a
      successful pregnancy in a cycle (manual treatment: no treatment) is 3.20 (95%
      confidence interval = 1.55-8.4). CONCLUSIONS: The data trend across these studies
      suggests that this innovative site-specific protocol of manual soft-tissue
      therapy facilitates fertility in women with a wide array of adhesion-related
      infertility and biomechanical reproductive organ dysfunction. The therapy,
      designed to improve function by restoring visceral, osseous, and soft-tissue
      mobility, is a nonsurgical, noninvasive manual technique with no risks and few,
      if any, adverse side effects or complications. As such, it should be considered a
      new adjunct to existing medical infertility treatments.

PMID- 15266277
TI  - Voluntary HIV counseling and testing of pregnant women--an assessment of
      compliance with Michigan public health statutes.
AB  - OBJECTIVES: First, to evaluate compliance with Michigan's laws mandating
      universal, voluntary HIV counseling and testing (VCT) of all pregnant women who
      provide informed consent (ie, the "opt-out strategy"). Second, to assess the
      acceptability of and agreement to VCT. METHODS: Women who delivered a live infant
      at a large, urban academic medical center were interviewed before hospital
      discharge. Obstetric and prenatal medical records were abstracted to document
      that VCT was offered, accepted, or declined and that pre- and posttest counseling
      were provided and test results noted. RESULTS: Our survey of 491 postpartum women
      interviewed from February 1998 through January 1999 revealed that 83% reported
      that they were offered VCT; of those, 95% reported that they had agreed to
      testing. Uninsured women were least likely to undergo VCT; no other demographic,
      social, or behavioral characteristics were associated with VCT. Nor was VCT more
      likely to occur according to providers' different practice settings (ie,
      "private" vs publicly funded). Most women reported that they did not find VCT
      offensive or threatening, although only 49% reported that they felt "very
      comfortable," refusing testing. CONCLUSION: These results suggest the opt-out
      strategy for VCT, as currently practiced in Michigan, can effectively promote the
      US Public Health Service testing goals. Offering VCT with the understanding that
      it may be refused without risk is essential. Additional educational interventions
      about HIV infection during pregnancy and perinatal HIV-transmission interruption
      were requested by women in our study and should be widely promoted. Given that
      95% of women agreed to VCT, mandatory testing without consent is not needed to
      achieve federal testing benchmarks and seems ethically problematic.

PMID- 15266279
TI  - Online patient-education options.

PMID- 15266278
TI  - Case-control study of factors associated with intrauterine fetal deaths.
AB  - OBJECTIVE: To study the characteristics of pregnancies that resulted in
      stillbirth and to determine which may possibly predict intrauterine fetal death
      (IUFD). STUDY DESIGN: A total of 161 singleton pregnancies resulting in
      stillbirth at Nottingham City Hospital from 1991 to 1997 were compared with 499
      live births randomly selected from the same period of time. The variables studied
      were the following: customized birth weight for gestational age, fetal sex,
      histopathologic cause of IUFD, maternal age, ethnic group, parity, maternal body
      mass index (BMI), smoking habit, and maternal blood group. RESULTS: In 54.7% of
      the cases of stillbirth at our institution women presented with reduction or
      absence of fetal movements before the diagnosis of IUFD. Almost half of the
      stillbirths (48.4%) were small for gestational age (< 10th percentile) on the
      basis of gestational age-specific weight. The difference in customized birth
      weight between stillbirths and live births was statistically significant (P
      <.0001). Increased maternal body mass index (BMI) was positively associated with
      stillbirth rate (P <.001), as was increased maternal age (P =.0012). Women with
      blood group O (P =.014) had an even higher stillbirth rate. There was no
      association between stillbirth rate and maternal ethnic group, maternal smoking,
      maternal Rhesus status, or fetal sex. CONCLUSIONS: This study found that almost
      half of stillborn babies were small for gestational age. Reduced fetal activity
      should be investigated thoroughly, with formal measurement of fetal growth as
      part of this assessment. Maternal blood group and maternal age were found to be
      important factors in IUFD. Smoking was not confirmed in this study to be a
      significant factor.

PMID- 15266280
TI  - Case 5--a 38-year-old man presented to Kijabe Mission Hospital with a swollen,
      draining right foot.

PMID- 15266281
TI  - Evidence-based medicine in managed care: a survey of current and emerging
      strategies.
AB  - BACKGROUND: Evidence-based medicine is the "conscientious application of
      scientific best practice by clinicians in concert with patient understanding and
      values." Recent studies by the Institute of Medicine, RAND, and others have
      called attention to the gap between scientifically supported approaches to care
      and day-to-day practice by clinicians. Compounding the problem of non-adherence
      by providers, researchers have observed that patient compliance also falls short.
      As a result, avoidable costs from inappropriate variability in practice patterns
      coupled with patient noncompliance are a significant focus of managed care.
      Managed care plans play a key role in the selection of providers by consumers and
      in the design of benefits programs by employers. Avoidable costs from misuse,
      overuse, and under-use of care from clinicians is a strategic focus for health
      plans. The evidence upon which a plan makes coverage decisions and the
      incorporation of evidence in programs targeting providers, employers, and
      consumers was a focus of this study. METHODOLOGY: A Delphi survey and 2-day
      interactive sessions with 128 clinical program directors and medical officers
      from 89 health plans were the primary methods used in this descriptive analysis.
      To test participant applications of evidence-based medicine in health plan
      medical management strategy, 3 conditions were used for illustrative purpose:
      managing rheumatoid arthritis, increasing remission in depression, and reducing
      heart disease among diabetics. Each provided a unique challenge to plans in terms
      of condition prevalence, strength of evidence, and cost. KEY FINDINGS: Health
      plans incorporate evidence-based medicine in 5 areas overseen by medical
      management: (1) coverage decisions wherein improvements in pharmaceutical and
      therapeutic review processes are sought, (2) disease management efforts wherein
      increased attention to secondary prevention is desirable, (3) provider profiling
      wherein increased use of adherence measures comparing practices is a focus, (4)
      pay-for-performance programs linking physician adherence to financial incentives,
      and (5) consumer-directed care programs wherein patient compliance to evidence
      based treatment directives is the focus. Factors that influence a plan's approach
      to a patient population include prevalence of the condition, the strength of
      evidence about a particular diagnostic or prognostic strategy, costs associated
      with the condition, and the influence of employers in coverage decisions.
      CONCLUSION: Evidence-based medicine is the foundation for significant activity
      among plans to increase physician and patient adherence. There remain significant
      challenges in the implementation of evidence-based care management by plans,
      including the willingness of plans to agree on evidence-based guidelines, the
      willingness of employers to pay for evidence-based interventions, the balance of
      short- and long-term benefits for evidence-based interventions where secondary
      prevention is a consideration, and substantial distrust among providers.

PMID- 15266285
TI  - Muscle relaxants in the treatment of myofascial face pain. A literature review.
AB  - Among the different pharmacological approaches that could be adopted in the
      treatment of myofascial pain of masticatory muscles, attention has to be paid to
      muscle relaxants drugs, since very few studies evaluated their efficacy, despite
      most authors suggest their use. The present paper is a critical review of the
      literature on the use of the most common drugs with muscle relaxant effects
      (benzodiazepines, tricyclic antidepressants) and of a muscle relaxant drug
      (tizanidine hydrochloride) in the treatment of such condition. From literature
      data it emerged that these drugs had phases of alternate enthusiasm,
      characterized by a not constant clinical use and a fair interest in research.
      Nevertheless, within all the limitations that have been discussed in this paper,
      the use of muscle relaxants in patients with myofascial pain of masticatory
      muscles seems to be justifiable, even though further research is needed to verify
      their usefulness in terms of risk-benefit ratio.

PMID- 15266286
TI  - Maxillary post-traumatic outcome correction. Literature review and personal
      experience. Part II: loss of maxillary substance (free grafts of autologous
      bone).
AB  - Loss of maxillary substance following trauma varies significantly in relation to
      the dimensions, site and type of tissue involved. Anatomical maxillary
      interruptions, loss of dental elements and consequent bone re-absorption give
      rise to altered chewing, swallowing and speech functions. Treatment of
      pathological conditions over the years has seen the development of surgical
      protocols designed to achieve simultaneous aesthetic and functional restoration
      of the stomatognatic apparatus. The advent of osteointegrated implantology and
      continual progress in pre-prosthesis surgical techniques have undoubtedly
      revolutionised established approaches to prosthetic rehabilitation by introducing
      the concept of supported implant prostheses. The implantation protocols used are
      a safe and reproducible treatment method suitable for adequate anchorage of such
      prosthetic implants; the application of such protocols in any case is
      subordinated to the presence of adequate morpho-volumetric bone at the skeletal
      bases. Depending on the entity of maxillary loss of substance, the reconstruction
      methods we propose, in agreement with numerous other authors, are based on the
      use of free and free-revascularised autologous bone grafts or, even more
      recently, the application of osteogenetic distraction techniques. The purpose of
      this article is to evaluate treatment of loss of maxillary substance following
      trauma by means of non-revascularised free flaps. The use of free grafts of
      autologous bone is elective in patients presenting bone deficits less than 6 cm
      with and/or without upkeep of maxillary and mandibular cortical bone continuity
      but without compromise to the integrity and trophism of the soft tissues.

PMID- 15266287
TI  - [Treatment of curved canals: from stainless steel to nickel titanium].
AB  - Endodontic treatment of curved canals is always more difficult than straight
      canals, especially for the apical zone preparation: root canals may present
      several curvatures in different space directions. From an anatomical point of
      view root canals with accentuated curvatures are a very frequent event (more than
      we might think); radiological exams, in fact, give us only a 2D image, and we can
      observe mesial or distal curvatures but not those in the oral or buccal
      direction. However, all root canals have curvatures of some degrees; even those
      that appear straight. Because of this, endodontitis have made many attempts to
      overcome these problems and manage to have a good preparation in curve canal. The
      authors analyse all endodontic techniques (step back, step down, crown down,
      balanced forces) codified in the course of the years, to prepare curved canals;
      they both in shape or in materials. It's fundamental for the endodontist to have
      a specific technique to treat curved canals to allow a good, wide preparation; in
      this way it's possible to make a better and tridimensional filling of the
      endodontic space above all in the tipical zone.

PMID- 15266288
TI  - Drugs in oral surgery. Brief guidelines for adult patients.
AB  - Drugs administrable in oral surgery for adult patients are antiseptics
      antibiotics, antiinflammatory-analgesics and sedative-hypnotics. Such drugs can
      be administered before, during or after oral surgery. Sedative-hypnotics can be
      administered before or during oral surgery in order to control the patient's
      anxiety. Anti-inflammatory-analgesics, on the other hand, can be administered
      before or after oral surgery to lower edema and pain. For this purpose, FANS are
      the most commonly used drugs but, in more traumatic oral surgery, the
      administration of a single pre-surgery dose of corticosteroids is suitable. As
      regards, antibiotics have to be given from 15 min to 1 h before oral surgery and
      continued or otherwise for 24-48 h depending on the dosage. post-surgery
      infection onset, in fact, is higher within 3 h after oral surgery.

PMID- 15266289
TI  - [Genetic and microbiologic tests in periodontal disease].
AB  - AIM: The presence of genetic polymorphisms IL-1A and IL-1B was demonstrated to be
      associated to an increased clinical severity of Periodontitis. The aim of our
      study was to verify the existence of a relationship between such genetic
      polymorphisms and pathogenic variations of Actinobacillus actinomycetemcomitans
      (Aa), Prevotella intermedia (Pi) and Porphyromonans gingivalis (Pg), in patients
      with periodontitis before and after active therapy. METHODS: Twenty-five patients
      were randomly selected among those attending the Department of Periodontology,
      University of Bologna, on the basis of radiographic and clinical data. At the end
      of active therapy, subjects had to undergo "PST" test. RESULTS: The "PST" was
      positive in 32% (8 out of 25) of patients; the majority of them (4 out of 8) were
      classified ADA IV, 3 were ADA III and 1 was ADA I (p > 0.05). All subjects with
      good hygiene therapy (13 out of 24 patients) have shown a reduced bacterial count
      after active clinical therapy (Fisher test p = 0.03). CONCLUSION: No
      statistically significant association was observed between positivity to "PST"
      and severity of periodontal disease.

PMID- 15266290
TI  - [Antibacterial effect of Nd:YAG laser in periodontal pockets decontamination: a
      in vivo study].
AB  - AIM: Tha aim of this paper is to assess the effects in vivo of the Nd: Yag laser
      on gingival microflora in patients periodontally at risk. METHODS: An
      investigation has been carried out on 5 patients suffering from serious
      periodontal disease, with a sub-gingival check-up a week after the treatment. The
      selected patients presented either a relapse after the raising of a traditional
      flap, or showed acute phenomena and were, therefore, treated with a laser with
      the propedeutic intention of surgery; or they refused traditional surgical
      therapy or presented systematic pathologies that could not be included in the
      appropriate protocol. Pockets were chosen that had a probe depth of between 5-8
      mm, an optic fibre probe was pushed as far as possible into the probe depth, for
      about 1 minute per site, 5 times, at 30 second intervals. The samples, taken in
      order to calculate bacteria colonies, were carried out before using the laser,
      immediately after and, again, 1 week later. RESULTS: All the sites showed a
      slight reduction in the quantity of colonies forming immediately after the Nd:Yag
      laser application, while a week later, only if clinical inflammation appeared to
      be resolved, the bacteria forming colonies seemed to be reduced. CONCLUSION: From
      this study it can be concluded that the use of the Nd:Yad laser represents, in
      mild and average periodontitis, a therapeutic aid to scaling and root planing
      and, in the same way, in serious periodontitis for traditional surgical therapy.

PMID- 15266291
TI  - [Set up of in vitro methods able to detect the safety of astringent liquids].
AB  - AIM: Most of dental operators agree about a gengival retraction impregnated cord
      in order to obtain an accurate and overwide dental impression. Hemostatic agents
      allow the formation of the primary coagulum that determines/causes the retraction
      of gum connective. Sometimes these astringent liquids cause local inflammation
      reaction as reported in literature. Aim of this work was the evaluation of the
      cytotoxic and inflammatory action of the most common astringent liquid on human
      gum primary cells by in vitro tests. METHODS: For this purpose primary cultures
      of normal human oral keratinocytes were established, following used either as
      monolayer or as reconstituted model. All dental preparations were dissolved in
      CEC medium, diluted to the designed concentrations and applied to the cultured
      cells. The cytotoxicity was determined by using MTT test, able to evaluate the
      succinate dehydrogenase activity and therefore the cell viability. Control
      cultures were treated with CED alone, whereas sodium dodecyl sulphate (SDS) was
      used as a positive control. Furthermore, the inflammatory response, determined by
      measuring TNF-alpha and IFN-gamma release, was evaluated on a reconstituted
      multilayer human oral epidermis model. RESULTS: All agents tested showed a dose
      dependent increase in the cytotoxicity to normal human gingival keratinocytes
      over the dose range examined. In particular the results obtained suggest the
      higher toxicity of the Astringedent X compound. CONCLUSION: The results obtained
      from the present studies not only provide useful estimates of relative toxicities
      of these preparations to human oral mucose, but also can be useful as a standard
      for cytotoxic and inflammatory assessment of newly developed dental preparations
      to be topically applied to the oral mucosa. It is important to note, however,
      that the interpolation of these findings to in vivo conditions remains to be
      done.

PMID- 15266292
TI  - [Verification of maxillary and mandibular asymmetry via orthopantogram's
      analysis].
AB  - AIM: The purpose of this study was to analyse the homologous variables' symmetry
      (horizontal, vertical, angular and of area surface) of the right and left segment
      in the maxilla and in the mandible of subjects with a normal occlusion and a
      malocclusion. METHODS: Two-hundred and two orthopantomograms were analysed (162
      with malocclusion, 40 with normal occlusion). These points of reference were
      used: orbital, condilion, gonion, menton, point A (intersection point between the
      vertical line passing through the centre of the nasal septum and the horizontal
      line which links the 2 points O), point B (intersection point between the
      mandibular margin and the vertical line passing through point O) and point T
      (intersection point of A-Cn on the maxillary tuberosity). RESULTS: This study did
      not confirm any statistically significant differences between the right and left
      analysed variables studied in both groups. CONCLUSION: Orthopantomography may be
      a useful test in the screening for facial asymmetry.

PMID- 15266293
TI  - Gemination of maxillary incisors.
AB  - Gemination is defined as a shape anomaly of teeth caused by an incomplete
      division of a single tooth bud. Its aesthetic and functional implications usually
      require a complex endodontic, restorative, periodontal, surgical, and orthodontic
      treatments. Three cases of gemination of maxillary incisors, resolved by
      different therapeutic approaches, are reported. The 1st case (germination of 2.1)
      was resolved by a simple crown-plasty. The 2nd case (gemination of 1.1 and 2.1)
      was resolved by a crown-plasty of 2.1 and an interradicular section of 1.1 with
      extraction of lateral root. The 3rd case (2.2 supernumerary and gemination of
      1.2) was resolved by sacrifice of 1.2, extraction of 2.2 and its implantation in
      1.2 region. In order to obtain an acceptable aesthetic and functional
      restoration, as in the cases presented, a good team-work, where all the
      specialists contribute to the selection of the more suitable treatment possible,
      is mandatory.

PMID- 15266294
TI  - Calcifying epithelial odontogenic (Pindborg) tumor. A clinical case.
AB  - Calcifying epithelial odontogenic tumor (CEOT), Pindborg tumor, is a rare benign
      odontogenic neoplasm representing about 0.4-3% of all odontogenic tumors. This
      tumor more frequently affects adults in an age range of 20-60 years, with a peak
      of incidence between 40 and 60 years. About 190 cases of CEOT have been reported
      in the dental literature. Fifty-two percent of cases of CEOT is associated with a
      tooth impacted and/or displaced by the tumor. The primary CEOT has a recurrence
      rate of 10-15%, after total excision, and its malignant transformation is a very
      rare occurrence. The authors report a case of primary intra-osseous CEOT,
      embedding the mandibular right second molar, in a 24 year-old male. Radiographs
      showed a well-defined unilocular osteolytic lesion, swelling and reabsorbing the
      mandible and displacing the inferior alveolar nerve. It was possible to perform
      conservative surgical treatment consisting of the enucleation of the tumor
      together with a portion of tumor-free bone cavity margin and the debridement of
      the inferior alveolar neuro-vascular bundle, which was surrounded by a tumor
      capsule-like structure. The postoperative histological examination of the tumor
      revealed typical benign features. The differential diagnosis and work-up of the
      tumor treatment are discussed in relation with its histological typing and
      localization in the jaws.

PMID- 15266295
TI  - Further evidence for paternal inheritance of mitochondrial DNA in the sheep (Ovis
      aries).
AB  - The mitochondrial DNA of 172 sheep from 48 families were typed by using PCR-RFLP,
      direct amplification of the repeated sequence domain and sequencing analysis. The
      mitochondrial DNA from three lambs in two half-sib families were found to show
      paternal inheritance. Our findings provide direct evidence of paternal
      inheritance of mitochondria DNA in sheep. A total of 12 highly polymorphic
      microsatellite markers, which mapped on different chromosomes, were employed to
      type the sheep population to confirm family relationships. Possible mechanisms of
      paternal inheritance are discussed.

PMID- 15266296
TI  - Fine-scale estimation of outcrossing in western redcedar with microsatellite
      assay of bulked DNA.
AB  - Western redcedar (Thuja plicata, Cupressaceae) is a self-fertile conifer with a
      mixed mating system and significant variation for outcrossing among populations.
      In this paper, we conducted a fine-scale study of mating system variation to
      identify correlates of outcrossing in natural populations. We examined variation
      for outcrossing within and among individual trees, and describe a new method to
      estimate outcrossing using bulked DNA samples. Bulking (assaying DNA tissues from
      several individuals simultaneously) increases the experimental power without
      increasing the experimental effort. We sampled 80 trees from four natural
      populations in southwestern British Columbia. From each tree, we sampled from up
      to six crown positions (three heights and inner vs outer branches). From each
      position, two samples of three seedlings each were bulked before DNA extractions.
      Using four microsatellite loci, we obtained outcrossing rates for each tree and
      for each of the six crown positions. We found individual tree selfing rates to
      increase with tree height in all four populations, but selfing rates did not
      differ among crown positions. The higher selfing rate of larger trees is probably
      due to their greater proportional contribution to local pollen clouds. Individual
      tree outcrossing rates ranged from 22 to 100% and the population outcrossing
      rates from 66 to 78%. Missed alleles due to bulking and the estimation method
      used both cause a downward bias in outcrossing rates, so that these estimates are
      probably lower than the actual outcrossing rates. Nevertheless, the trends we
      observed are not affected by systematic biases of estimation.

PMID- 15266297
TI  - Nuclear mitochondrial pseudogenes as molecular outgroups for phylogenetically
      isolated taxa: a case study in Sphenodon.
AB  - 'Living fossil' taxa, by definition, have no close relatives, and therefore no
      outgroup to provide a root to phylogenetic trees. We identify and use a molecular
      outgroup in the sole extant lineage of sphenodontid reptiles, which separated
      from other reptiles 230 million years ago. We isolated and sequenced a partial
      nuclear copy of the mitochondrial cytochrome b gene. We confirm the copy is
      indeed not mitochondrial, is older than all extant mitochondrial copies in
      Sphenodon (tuatara), and is therefore useful as a molecular outgroup. Under
      phylogenetic analysis, the nuclear copy places the root of the tuatara
      mitochondrial gene tree between the northern and the southern (Cook Strait)
      groups of islands of New Zealand that are the last refugia for Sphenodon. This
      analysis supports a previous mid-point rooted mitochondrial gene tree. The
      mitochondrial DNA tree conflicts with allozyme analyses which place a Cook Strait
      population equidistant to all northern and other Cook Strait populations. This
      population on North Brother Island is the only natural population of extant S.
      guntheri; thus, we suggest that the current species designations of tuatara
      require further investigation.

PMID- 15266298
TI  - Inheritance and dominance of self-incompatibility alleles in polyploid
      Arabidopsis lyrata.
AB  - Natural populations of diploid Arabidopsis lyrata exhibit the sporophytic type of
      self-incompatibility system characteristic of Brassicaceae, in which complicated
      dominance interactions among alleles in the diploid parent determine self
      recognition phenotypes of both pollen and stigma. The purpose of this study was
      to investigate how polyploidy affects this already complex system. One tetraploid
      population (Arabidopsis lyrata ssp kawasakiana from Japan) showed complete self
      compatibility and produced viable selfed progeny for at least three generations
      subsequent to field collection. In contrast, individuals from a second tetraploid
      population (A. lyrata ssp petraea from Austria) were strongly self-incompatible
      (SI). Segregation of SI genotypes in this population followed Mendelian patterns
      based on a tetrasomic model of inheritance, with two to four alleles per
      individual, independent segregation of alleles, and little evidence of dosage
      effects of alleles found in multiple copies. Similar to results from diploids,
      anomalous compatibility patterns involving particular combinations of individuals
      occurred at a low frequency in the tetraploids, suggesting altered dominance in
      certain genetic backgrounds that could be due to the influence of a modifier
      locus. Overall, dominance relationships among S-alleles in self-incompatible
      tetraploid families were remarkably similar to those in related diploids,
      suggesting that this very important and complicated locus has not undergone
      extensive modification subsequent to polyploidization.

PMID- 15266299
TI  - Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and
      preliminary association with the diagnosis of asthma.
AB  - Toll-like receptor 6 (TLR6) is one of a series of highly conserved innate immune
      receptors. We resequenced TLR6 in DNA samples from 24 African Americans, 23
      European Americans, and 24 Hispanic Americans, identifying 53 SNPs, 22 with an
      allele frequency >5%. Significant differences in SNP frequencies among the three
      populations were noted. In all, 11 SNPs caused amino-acid changes, including one
      with a frequency >5% in all three populations. Utilizing this SNP (Ser249Pro), we
      performed exploratory nested case-control disease-association studies, including
      one involving 56 African Americans with asthma and 93 African American controls.
      The minor allele of this SNP was associated with decreased risk for asthma (odds
      ratio 0.38, 95% CI 0.16-0.87, P=0.01), an effect consistent with the known
      biology of the toll-like receptors. Although replication of this finding in
      other, larger samples is needed, variation in TLR6 may have relevance to the
      pathogenesis of immunologically mediated diseases.

PMID- 15266302
TI  - Inverted duplications: how many of them are mosaic?
AB  - The best-known situation indissolubly linked to mosaicism is the uniparental
      disomy where a trisomic or monosomic zygote develops at least one cell line with
      46 chromosomes. The mosaicism normal/abnormal cell lines may remain confined to
      placenta or persist in the embryo. Here, we describe a second situation that
      might also be indissolubly linked to a mosaic condition or at least to a confined
      placental mosaicism. We analysed the case of a mosaicism del(8p)/inv dup(8p)
      found in prenatal diagnosis. We had already demonstrated that the first product
      of the abnormal meiotic recombination at the basis of the inv dup rearrangements
      is a dicentric chromosome. Its breakage leads to the formation of a deleted and
      an inv dup chromosome. Although we had previously assumed that the dicentric
      underwent a breakage at meiosis II so that the zygote inherited the inv dup
      chromosome, our findings and those of others indeed indicate that the dicentric
      may be inherited in the zygote and that it might persist as such in early
      postzygotic stages, then undergoing different breakages in different cells
      leading to different abnormal chromosomes, either deleted or duplicated.
      Selection versus the most viable cell line(s) results either in a confined
      placental mosaicism with the inv dup cell line as the only one present in the
      embryo or in children with both the deleted and the inv dup cell lines.
      Phenotype/karyotype relationships in inv dup rearrangements must also take into
      account the influence of the other abnormal cell line during embryogenesis.

PMID- 15266301
TI  - Mutation analysis of five candidate genes in Chinese patients with hypospadias.
AB  - Hypospadias is the displacement of the urethral meatus from the tip of the glans
      to the ventral side of the phallus. During fetal development, SRY, SOX9, WT1,
      SRD5A2 and AR are important at different stages in the differentiation and
      development of the male genital system. Mutations in these genes impair
      masculinization and may be associated with hypospadias. In order to explore these
      possibilities, we employed polymerase chain reaction and direct sequencing to
      analyze the coding regions of these five genes in 90 Chinese hypospadias
      patients. We found a total of 16 different mutations in SRD5A2, AR and WT1 in 24
      of these 90 patients. Seven mutations are novel. No mutation was found in SRY or
      SOX9. SNP V89L found in SRD5A2 was statistically significant between patients and
      controls. Our results indicated that mutations in SRD5A2, AR and WT1 were
      associated with hypospadias. In conclusion, mutations are frequently found in
      genes that control androgen action and metabolism, but are seldom found in genes
      active in the early phase of sex determination and differentiation. Mutations in
      AR, SRD5A2 or WT1 seem to be associated not only with hypospadias but also with
      micropenis.

PMID- 15266303
TI  - Complete genomic structure of the human nebulin gene and identification of
      alternatively spliced transcripts.
AB  - The giant nebulin protein is a fundamental structural component of the thin
      filaments of the striated muscle sarcomere. Nebulin binds to actin and the size
      of nebulin correlates with actin filament length, suggesting that nebulin may
      determine the length of the thin filaments during myofibrillogenesis. We have
      previously described the genomic organization of the 3' end of the nebulin gene
      (NEB), and identified 18 different NEB mutations in patients with autosomal
      recessive nemaline myopathy. Here we present the genomic organization of the
      entire nebulin gene, and the identification of numerous alternatively spliced
      mRNAs. The gene comprises 183 exons spanning 249 kb of the genomic sequence. The
      translation initiation codon is in exon 3, and the stop codon and the 3' UTR are
      in exon 183. There are four regions with alternatively spliced exons, that is,
      exons 63-66, 82-105, 143-144 and 166-177, giving rise to a number of different
      transcripts. The alternatively spliced exons 143-144 give rise to two different
      transcripts varying between muscle types and between muscles of different
      developmental stages. The alternatively spliced exons 166-177 express at least 20
      different transcripts in adult human tibialis anterior muscle alone. Preliminary
      results show several transcripts in both of the two remaining alternatively
      spliced regions. Extensive alternative splicing of NEB may explain why nemaline
      myopathy patients with homozygous truncating mutations show expression of the
      carboxy-terminus of the nebulin protein contrary to expectations. The use of
      alternative transcripts might also explain why severe phenotypes are rare among
      patients with two truncating mutations.

PMID- 15266304
TI  - A trio family study showing association of the lymphotoxin-alpha N26 (804A)
      allele with coronary artery disease.
AB  - Family-based studies to map susceptibility genes through linkage disequilibrium
      have been successful in early-onset diseases where parental-proband trios are
      readily collected, but are believed to be unworkable for late-onset diseases such
      as coronary artery disease (CAD). PROCARDIS is a European multicentre study that
      was designed to identify susceptibility genes for CAD. We have tested the
      transmission of a putatively functional allele, lymphotoxin-alpha N26 (804A), in
      more than 400 PROCARDIS trio families. The present study demonstrates association
      of this allele with CAD in white Europeans, a different ethnic group with a
      heavier CAD burden than the Japanese in which the association was initially
      identified, which suggests a broad relevance to CAD susceptibility. The
      practicalities of implementing a trio-family design for late-onset diseases are
      discussed.

PMID- 15266305
TI  - Polymorphisms of the PRNP gene in Chinese populations and the identification of a
      novel insertion mutation.
AB  - The two common polymorphisms (385A > G: M129V and 655G > A: E219 K) in the human
      prion gene (PRNP) play important roles in the pathogenesis of Creutzfeldt-Jakob
      diseases. We screened a total of 626 individuals, who represent three ethnic
      populations of China, Han, Hui, and Uyghur, for the two polymorphisms. The
      frequencies of M/M homozygote at residue 129 in these three groups differ
      significantly. The Han has a much higher frequency (98%) than Hui (85%) and
      Uyghur (60%). On the other hand, the frequencies of the E/E at residue 219 are
      higher in Uyghur (98%) and Hui (96%) than in Han (90%). We also investigated two
      other less common variants of PRNP, a silent substitution at residue 117 (351A >
      G: A117A), and one octapeptide-repeat deletion (1-OPRD) in the octapeptide-coding
      region. We found three Uyghur individuals with silent substitution at residue
      117. Four Hui (2.0%) and one Han (0.5%) donors were found to be heterozygous for
      1-OPRD. A novel three extra-repeat (72 bp) insertion within the octapeptide
      coding region was identified in one healthy 11-years-old Hui. Identical mutation
      was also found in her mother but not her father.

PMID- 15266306
TI  - Effect of placental function on fatty acid requirements during pregnancy.
AB  - The fetus has an absolute requirement for the n-3/n-6 fatty acids and
      docosahexaenoic acid (22:6 n-3; DHA) in particular is essential for the
      development of the brain and retina. Most of the fat deposition in the fetus
      occurs in the last 10 weeks of pregnancy. The likely rate of DHA utilisation
      during late pregnancy cannot be met from dietary sources alone in a significant
      proportion of mothers. De novo synthesis makes up some of the shortfall but the
      available evidence suggests that the maternal adipose tissue makes a significant
      contribution to placental transport to the fetus. The placenta plays a crucial
      role in mobilising the maternal adipose tissue and actively concentrating and
      channelling the important n-3/n-6 fatty acids to the fetus via multiple
      mechanisms including selective uptake by the syncytiotrophoblast, intracellular
      metabolic channelling, and selective export to the fetal circulation. These
      mechanisms protect the fetus against low long-chain polyunsaturated fatty acid
      (LCPUFA) intakes in the last trimester of pregnancy and have the effect of
      reducing the maternal dietary requirement for preformed DHA at this time. As a
      result of these adaptations, small changes in the composition of the habitual
      maternal diet before pregnancy are likely to be more effective in improving
      LCPUFA delivery to the fetus than large dietary changes in late pregnancy. There
      is little evidence that DHA intake/status in the second half of pregnancy affects
      visual and cognitive function in the offspring, but more studies are needed,
      particularly in children born to vegetarian and vegan and mothers who may have
      very low intakes of DHA.

PMID- 15266307
TI  - Changes in diet and physical activity in the 1990s in a large British sample
      (1958 birth cohort).
AB  - OBJECTIVES: To investigate whether adults studied in 1991 and 1999 (at ages 33
      and 42 y) improved their diet and their physical activity level, in the direction
      of recommendations issued during the same period. DESIGN: Longitudinal 1958
      British birth cohort study. SETTING: England, Scotland and Wales. PARTICIPANTS:
      All births, 3rd-9th March, 1958. A minimum of 11 341 participants provided data
      at 33 y, 11 361 at 42 y. MAIN OUTCOME MEASURES: Frequency of leisure time
      activity and consumption of (i) fried food, (ii) chips, (iii) wholemeal bread and
      (iv) fruit and salad/raw vegetables, at 33 and 42 y. RESULTS: Most people changed
      their physical activity and dietary habits over the 8-y period. About a third of
      men and women increased, and a third decreased their activity frequency. Findings
      for fried food consumption were similar. A significantly greater proportion of
      cohort members decreased their chips consumption (32%), rather than increased it
      (17%) and increased their fruit and salad consumption (30%), rather than
      decreased it (25%). In all, 26% of men and 33% of women consistently ate, or
      switched to eating mostly wholemeal bread, while 56% of men and 48% of women
      consistently ate less or switched to eating less. Social gradients were seen for
      activity and diet in 1991, but associations between social factors or body mass
      index and change in activity or diet were inconsistent. CONCLUSIONS: Lifestyle
      habits such as dietary intake and physical activity are slow to change. Current
      health promotion strategies may need to be supplemented with additional methods
      to affect the desired change in these habits.

PMID- 15266308
TI  - Immunoenhanced enteral nutrition, effect on inflammatory markers in head and neck
      cancer patients.
AB  - The aim of our study was to evaluate the effect of enteral nutrition supplemented
      with arginine in inflammatory markers in surgical head and neck cancer patients.
      A population of 29 patients with oral and laryngeal cancer were enrolled in a
      randomized trial. At surgery patients were randomly allocated to two groups: (a)
      patients receiving an enteral diet supplements with arginine (group I, n=14); (b)
      patients receiving an isocaloric, isonitrogenous enteral formula (group II,
      n=15). The mean age was 61.1+/-10.8 y (five females/24 males). Characteristics of
      the patients on enrollment were similar for the two groups. Prealbumin and
      transferrin improved in both groups. c-reactive protein (CRP) levels decreased in
      both groups, (group I: 134.5+/-62.5 vs 75.3+/-51 mg/dl:P<0.05) and (group II:
      103.6+/-62 vs 43.8+/-34.4 mg/dl:P<0.05). Interleukin-6 (IL-6) improved in both
      groups (group I: 20.35+/-11.2 vs 6.7+/-3.1 pg/ml:P<0.05) and (group II:22.8+/-40
      vs 9.9+/-17.7 pg/ml:ns). Tumoral necrosis factor alpha and lymphocytes did not
      change. In conclusion, both formulas improved IL-6 and CRP levels. Further
      studies are needed to determine whether type of formula is the key in these
      patients or genetic background play a main role in inflammatory response.

PMID- 15266309
TI  - Targeting cytotoxic T lymphocytes for cancer immunotherapy.
AB  - In light of their preeminent role in cellular immunity, there is considerable
      interest in targeting of cytotoxic T-lymphocytes to cancer. This review
      summarises the active and passive immunotherapeutic approaches under development
      to achieve this goal, emphasising how recent advances in tumour immunology and
      gene transfer have impacted upon this field.

PMID- 15266310
TI  - Frequent downregulation and loss of WWOX gene expression in human hepatocellular
      carcinoma.
AB  - The WWOX (WW-domain containing oxidoreductase) is a candidate tumour suppressor
      gene spanning the same chromosome region, 16q23, as the second most common
      fragile site (FS), FRA16D. Deletions detected by comparative genomic
      hybridisation (CGH) and loss of heterozygosity at microsatellite markers on
      chromosome 16q are common in many human cancers including hepatocellular
      carcinoma (HCC). The development of human HCC is closely associated with exposure
      to oncogenic viruses and chemical carcinogens, agents known to frequently target
      common FS. We examined the status of WWOX genomic DNA, RNA and protein in 18 cell
      lines derived from human HCC and found recurrent alterations of the gene. Loss of
      DNA copy-number confined to band 16q23 was detected by CGH in several cell lines.
      Although homozygous deletions of the WWOX gene were not detected, WWOX mRNA
      expression was absent or lower in 60% of cell lines. The occurrence of aberrant
      WWOX reverse transcription-PCR products with deletion of exons 6-8 correlated
      significantly with altered WWOX expression. All of the cell lines showing mRNA
      downregulation had a decreased or undetectable level of WWOX protein as
      demonstrated by Western blotting with antibody to WWOX. Furthermore, 13 out of
      the 18 cell lines expressed decreased levels or no WWOX protein when compared
      with normal liver. These results show that WWOX gene is frequently altered in HCC
      and raise the possibility that this gene is implicated in hepatocarcinogenesis.

PMID- 15266312
TI  - Role of urothelial cells in BCG immunotherapy for superficial bladder cancer.
AB  - Intravesical instillation of Bacillus Calmette-Guerin (BCG) is used for the
      treatment of superficial bladder cancer, both to reduce the recurrence rate of
      bladder tumour and to diminish the risk of progression. Since its first
      therapeutic application in 1976, major research efforts have been directed to
      decipher the exact mechanism of action of the BCG-associated antitumour effect.
      Bacillus Calmette-Guerin causes an extensive local inflammatory reaction in the
      bladder wall. Of this, the massive appearance of cytokines in the urine of BCG
      treated patients stands out. Activated lymphocytes and macrophages are the most
      likely sources of these cytokines, but at present other cellular sources such as
      urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guerin is
      internalised and processed both by professional antigen-presenting cells and
      urothelial tumour cells, resulting in an altered gene expression of these cells
      that accumulates in the presentation of BCG antigens and secretion of particular
      cytokines.

PMID- 15266311
TI  - An antagonist of retinoic acid receptors more effectively inhibits growth of
      human prostate cancer cells than normal prostate epithelium.
AB  - Screening of synthetic retinoids for activity against prostate carcinoma cell
      lines has identified antagonists of retinoic acid receptors (RARs) as potent
      growth inhibitors (Hammond et al, 2001, Br J Cancer 85, 453-462). Here we report
      that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310)
      abolished growth of prostate carcinoma cells from 14 out of 14 patients, with
      half-maximal inhibition between 200 and 800 nM. It had similar effects (at
      approximately 250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3.
      AGN194310 inhibited the growth of normal prostate epithelium cells less potently,
      by 50% at approximately 1 microM. The growth of tumour cells was also inhibited
      more than that of normal cells when RARbeta together with RARgamma, but not
      RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310
      arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the
      level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by
      mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis
      was caspase-independent: caspases were neither cleaved nor activated, and DNA
      fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability
      of AGN 194310 to induce apoptosis of prostate cancer cells and its differential
      effect on malignant and normal prostate epithelial cells suggests that this
      compound may be useful in the treatment of prostate cancer.

PMID- 15266313
TI  - Nuclear survivin as a biomarker for non-small-cell lung cancer.
AB  - Survivin inhibits apoptosis and promotes mitosis. We determined whether nuclear
      or cytoplasmic localisation of survivin predicts survival of 48 patients with
      resected non-small-cell lung cancer (NSCLC). Patients with nuclear staining of
      survivin had significantly worse survival (relative risk: 3.9, P=0.02).
      Therefore, survivin may be a biomarker for NSCLC.

PMID- 15266314
TI  - Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5
      protein in gastric aspirates.
AB  - Symptomatic oesophageal cancer is usually advanced and the prognosis poor.
      Lethality of symptomatic oesophageal cancer has motivated screening for these
      diseases earlier in their evolution, but reliable methods for early diagnosis
      remain elusive. We have demonstrated that dysregulated expression of
      minichromosome maintenance (MCM) proteins 2-7 is characteristic of early
      epithelial carcinogenesis, and that these key DNA replication initiation factors
      can be used as diagnostic markers for cervical and genito-urinary tract cancer.
      In this study, we investigated whether minichromosome maintenance protein 5
      (Mcm5) can be used to detect oesophageal cancer cells in gastric aspirates. Two
      monoclonal antibodies raised against His-tagged human Mcm5 were used in a time
      resolved immunofluorometric assay to measure Mcm5 levels in cells isolated from
      gastric aspirates of 40 patients undergoing gastroscopy for suspected or known
      oesophageal carcinoma or symptoms of dyspepsia. The test discriminated with high
      specificity and sensitivity between patients with and without oesophageal cancer
      (85% sensitivity (95% confidence interval (CI)=62-97%), 85% specificity (CI=66
      96%)), as demonstrated by the large area under the receiver operating
      characteristics curve (0.93 (95% CI=0.85-0.99)). Elevated levels of Mcm5 in
      gastric aspirates are highly predictive of oesophageal cancer. This simple test
      for oesophageal cancer is readily automated with potential applications in
      primary diagnosis, surveillance and screening.

PMID- 15266315
TI  - Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal
      cancer.
AB  - Proliferating cells, especially tumour cells, express a special isoenzyme of
      pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high
      affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with
      a low PEP affinity. In tumour cells, the dimeric form is usually predominant and
      is therefore termed Tumour M2-PK. The levels of Tumour M2-PK within tumours and
      in EDTA-plasma correlate with staging and the ability of the tumour cells to
      metastasise. Since most colorectal tumours grow intraluminally, it appeared
      interesting to determine whether Tumour M2-PK is detectable in the faeces of
      tumour patients. Stool samples were tested by ELISA from controls without
      colorectal cancer and colorectal cancer patients. Whereas Tumour M2-PK levels
      were low in the control group (mean value+/-s.e.m.: 3.3+/-0.4, n=144), they were
      high in the case of colorectal cancer (56.1+/-15.3, n=60). At a cutoff value of 4
      U ml(-1), the sensitivity was 73%. TNM and Dukes' classification of the tumours
      revealed a strong correlation between faecal Tumour M2-PK levels and staging. The
      determination of Tumour M2-PK in faeces provides a new promising screening tool
      for colorectal tumours.

PMID- 15266316
TI  - Positive peritoneal cytology in early-stage endometrial cancer does not influence
      prognosis.
AB  - The aim of this study was to assess the prognostic importance of positive
      peritoneal cytology in early-stage endometrial cancer. All 278 stage I and 53
      stage IIIA (without cervical involvement) endometrial cancer patients operated
      between 1980 and 1996, recorded at the Geneva Cancer registry, were included.
      Stage IIIA cancers were recategorised into 'cytological' stage IIIA (positive
      peritoneal cytology alone, n=33) and 'histological' stage IIIA (serosal or
      adnexal infiltration, n=20). Survival rates were analysed by Kaplan-Meier method
      and compared using log-rank test. The prognostic importance of cytology was
      analysed using a Cox model, accounting for other prognostic factors. The 5-year
      disease-specific survival of cytological stage IIIA cancer was similar to stage I
      (91 vs 92%) and better than histological stage IIIA cancer (50%, P<0.001). After
      adjustment for age, myometrial invasion, differentiation and radiotherapy,
      cytological stage IIIA patients were still at similar risk to die from
      endometrial cancer compared to stage I patients (hazard ratio (HR) 0.7, 95%
      confidence interval (CI): 0.18-2.3), while histological stage IIIA patients were
      at a four-fold increased risk to die from their disease (HR 4.2, 95% CI: 1.7
      10.3). This population-based study shows that positive peritoneal cytology in
      itself has no impact on survival of patients with localised endometrial cancer.
      Based on the present and previous studies, FIGO (Federation Internationale de
      Gynecologie et d'Obstetrique) might consider reviewing its classification system.

PMID- 15266317
TI  - Correlation of real-time haemoglobin oxygen saturation monitoring during
      photodynamic therapy with microvascular effects and tissue necrosis in normal rat
      liver.
AB  - Photodynamic therapy (PDT) requires a photosensitising drug, light and oxygen.
      While it is known that the haemoglobin oxygen saturation (HbSat) can be altered
      by PDT, little has been done to correlate this with microvascular changes and the
      final biological effect. This report describes such studies on the normal liver
      of rats sensitised with aluminium disulphonated phthalocyanine. In total, 50 J of
      light at 670 nm, continuous or fractionated at 25 or 100 mW, was applied with a
      single laser fibre touching the liver surface. HbSat was monitored continuously
      1.5-5.0 mm from the laser fibre using visible light reflectance spectroscopy
      (VLRS). Vascular shutdown was assessed by fluorescein angiography 2-40 min after
      light delivery. Necrosis was measured at post mortem 3 days after PDT. In all
      treatment groups at a 1.5 mm separation, HbSat fell to zero with little recovery
      after light delivery. At 2.5 mm, HbSat also decreased during light delivery,
      except with fractionated light, but then recovered. The greatest recovery of
      fluorescein perfusion after PDT was seen using 25 mW, suggesting an
      ischaemia/reperfusion injury. Necrosis was more extensive after low power and
      fractionated light than with 100 mW, continuous illumination. We conclude that
      VLRS is a useful technique for monitoring HbSat, although the correlation between
      HbSat, fluorescein exclusion and necrosis varied markedly with the light delivery
      regimen used.

PMID- 15266318
TI  - Living arrangements and place of death of older people with cancer in England and
      Wales: a record linkage study.
AB  - The main objectives of the study were to (1) see whether the household
      circumstances of people aged 50 years and over with cancer, and trends in these,
      differ from those of the rest of the population and (2) whether living
      arrangements and presence and health status of a primary coresident are
      associated with place of death among older people dying of cancer and those dying
      from other causes. The design included prospective record linkage study of people
      aged 50 years and over included in a 1% sample of the population of England and
      Wales (the Office for National Statistics Longitudinal Study). The main outcome
      measures comprised family and household type, and death at home. The household
      circumstances of older people with cancer were very similar to those of the rest
      of the population of the same age and both showed a large increase in living
      alone, and decrease in living with relatives, between 1981 and 1991. The primary
      coresident of cancer sufferers who did not live alone was in most cases a spouse,
      with much smaller proportions living with a child, sibling or other person. In
      all, 30% of spouse, and 23% of other, primary coresidents had a limiting long
      term illness. Compared with people who lived alone in 1991, odds of a home death
      among those dying of cancer between 1991 and 1995 were highest for those who
      lived with a spouse who had no limiting long-term illness (odds ratio (OR) 2.52,
      95% confidence interval (CI) 2.15-2.97) and raised for those living with a spouse
      with a long-term illness (OR 2.14, CI 1.79-2.56) and those living with someone
      else who was free of long-term illness (OR 2.13, CI 1.69-2.68). Higher
      socioeconomic status, both individual and area, was positively associated with
      increased chance of a home death, while older age reduced the chance of dying at
      home. The changing living arrangements of older people have important
      implications for planning and provision of care and treatment for cancer
      sufferers.

PMID- 15266319
TI  - Phase II study of capecitabine and mitomycin C as first-line treatment in
      patients with advanced colorectal cancer.
AB  - This study was designed to assess the safety and efficacy of capecitabine and
      mitomycin C (MMC) in previously untreated patients with advanced colorectal
      cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided
      in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21
      days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every
      6 weeks for a total of four courses. The median age was 70 years (range 24-85)
      and the majority of patients (86.9%) were of performance status 1/2. The most
      common metastatic site was liver. In all, 84 patients were assessable for
      response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further
      33.3% of patients achieved stable disease over 12 weeks. There was good symptom
      resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot
      syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and
      MMC have shown encouraging activity with a favourable toxicity profile, a
      convenient administration schedule, and could be considered for patients deemed
      unsuitable for oxaliplatin and irinotecan combinations.

PMID- 15266321
TI  - Assessing health risks of complementary alternative medicines in cancer patients.

PMID- 15266320
TI  - Predictive role of positron emission tomography (PET) in the outcome of lymphoma
      patients.
AB  - An extensive analysis of the reliability of positron emission tomography (PET)
      after induction treatment in patients with Hodgkin's disease (HD) or aggressive
      non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or
      aggressive NHL (n=34) were studied with both PET and CT scans following standard
      chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy.
      Histopathological analysis was performed when considered necessary. After
      treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as
      compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41
      CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0
      out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9
      and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five
      patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%)
      cases, persistent lymphoma and was confirmed at histopathological examination.
      Two HD patients who were PET(-)/CT(+) (with large residual masses in the
      mediastinum or lung) were submitted to biopsy, which in both cases revealed only
      fibrosis. In HD and aggressive NHL patients, PET positivity after induction
      treatment is highly predictive for the presence of residual disease, with
      significant differences being observable in terms of RFS. PET negativity at
      restaging strongly suggests the absence of active disease; histopathological
      verification is important in patients who show PET positivity.

PMID- 15266323
TI  - Assessment of clonal relationships in ipsilateral and bilateral multiple breast
      carcinomas by comparative genomic hybridisation and hierarchical clustering
      analysis.
AB  - The issue of whether multiple, ipsilateral or bilateral, breast carcinomas
      represent multiple primary tumours or dissemination of a single carcinomatous
      process has been difficult to resolve, especially for individual patients. We
      have addressed the problem by comparative genomic hybridisation analysis of 26
      tumours from 12 breast cancer patients with multiple ipsilateral and/or bilateral
      carcinoma lesions. Genomic imbalances were detected in 25 of the 26 (96%)
      tumours. Using the genomic imbalances detected in these 26 lesions as well as
      those previously found by us in an independent series of 35 unifocal breast
      carcinomas, we compared a probabilistic model for likelihood of independence with
      unsupervised hierarchical clustering methodologies to determine the clonal
      relatedness of multiple tumours in breast cancer patients. We conclude that CGH
      analysis of multiple breast carcinomas followed by unsupervised hierarchical
      clustering of the genomic imbalances is more reliable than previous criteria to
      determine the tumours' clonal relationship in individual patients, that most
      ipsilateral breast carcinomas arise through intramammary spreading of a single
      breast cancer, and that most patients with bilateral breast carcinomas have two
      different diseases.

PMID- 15266324
TI  - Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends
      on MEK/ERK activation.
AB  - Testicular germ cell tumours (TGCT) represent the most common malignancies in
      young males. Whereas in 1970s, the survival rate in patients with metastatic
      testicular tumours was only 5%, these days, 80% of the patients treated by modern
      chemotherapy will survive their disease. The drug that revolutionised the cure
      rate for patients with metastatic testicular tumours was
      cisdiamminedichloroplatinum (cisplatin, CDDP). In vitro experiments on neoplastic
      germ cell lines showed that their exquisite sensitivity to CDDP could be
      attributed to p53-dependent and -independent pathways. Applying cDNA macroarray,
      semiquantitative RT-PCR and Western blot analyses, blocking experiments, caspase
      activity assays, and morphological methods, we sought here to define the p53
      independent pathway(s) involved in the CDDP-induced apoptosis. For this purpose,
      we used the human TGCT cell line NCCIT, the mutated p53 of which is known to
      remain inactive during the course of CDDP-induced apoptosis. Our experiments
      showed that within hours of CDDP application, two prototype members of the
      'mitogen-activated protein kinase' (MAPK) family, designated 'MAPK ERK kinase'
      (MEK) and 'extracellular signal-regulated kinase' (ERK), were dually
      phosphorylated and caspase-3 became active. Functional assays using MEK
      inhibitors demonstrated that the phosphorylation of MEK and ERK was required for
      the activation of caspase-3 as the executing caspase. Interestingly, experiments
      with the human malignant germ cell line NTERA, which is known to possess wild
      type p53, revealed the same results. Thus, our data suggest that CDDP mediates
      its p53-independent apoptosis-inducing effect on the malignant human testicular
      germ cells--at least partially--through activation of the MEK-ERK signalling
      pathway. July 2004

PMID- 15266325
TI  - The relationship between T-lymphocyte subset infiltration and survival in
      patients with prostate cancer.
AB  - The relationship between tumour stage, T-lymphocyte subset infiltration and
      survival was examined in patients with prostate cancer (n=80). On multivariate
      analysis PSA (HR 2.47, 95% CI 1.27-4.83, P=0.008) and CD4+ T-lymphocyte count (HR
      2.29, 95% CI 1.25-4.22, P=0.008) had independent significance. Increased CD4+ T
      lymphocyte infiltration within the tumour was stage independent and associated
      with poor outcome in patients with prostate cancer.

PMID- 15266326
TI  - Synchrotron radiation-based experimental determination of the optimal energy for
      cell radiotoxicity enhancement following photoelectric effect on stable iodinated
      compounds.
AB  - This study was designed to experimentally evaluate the optimal X-ray energy for
      increasing the radiation energy absorbed in tumours loaded with iodinated
      compounds, using the photoelectric effect. SQ20B human cells were irradiated with
      synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell
      treatments were compared to the control: cells suspended in 10 mg ml(-1) of
      iodine radiological contrast agent or cells pre-exposed with 10 microM of iodo
      desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell
      survival. Cells irradiated with both iodine compounds exhibited a radiation
      sensitisation enhancement. Moreover, it was energy dependent, with a maximum at
      50 keV. At this energy, the sensitisation calculated at 10% survival was equal to
      2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells
      pretreated with IUdR had higher sensitisation factors over the energy range than
      for those suspended in iodine contrast agent. Also, their survival curves
      presented no shoulder, suggesting complex lethal damages from Auger electrons.
      Our results confirm the existence of the 50 keV energy optimum for a binary
      therapeutic irradiation based on the presence of stable iodine in tumours and an
      external irradiation. Monochromatic synchrotron radiotherapy concept is hence
      proposed for increasing the differential effect between healthy and cancerous
      tissue irradiation.

PMID- 15266327
TI  - Incidence of cerebral metastases in patients treated with trastuzumab for
      metastatic breast cancer.
AB  - Trastuzumab is an effective treatment for patients with metastatic breast cancer
      (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has
      been noted in patients receiving trastuzumab. A retrospective chart review was
      conducted of 100 patients commencing trastuzumab for metastatic breast cancer
      from July 1999 to December 2002, at the Christie Hospital. Seven patients were
      excluded; five patients developed central nervous system metastases prior to
      starting trastuzumab, and inadequate data were available for two. Out of the
      remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients
      have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of
      the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18
      (78%) had visceral disease. Univariate analysis showed a significant association
      between the development of cerebral disease and both hormone receptor status and
      the presence of visceral disease. In conclusion, a high proportion of patients
      with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2
      positive breast cancer may have a predilection for the brain, or trastuzumab
      therapy may change the disease pattern by prolonging survival. New strategies to
      address this problem require investigation in this group of patients.

PMID- 15266328
TI  - Is the association of birth weight with premenopausal breast cancer risk mediated
      through childhood growth?
AB  - Several studies have found positive associations between birth weight and breast
      cancer risk at premenopausal ages. The mechanisms underlying this association are
      not known, but it is possible that it may be mediated through childhood growth.
      We examined data from a British cohort of 2176 women born in 1946 and for whom
      there were prospective measurements of birth weight and of body size throughout
      life. In all, 59 breast cancer cases occurred during follow-up, 21 of whom were
      known to be premenopausal. Women who weighed at least 4 kg at birth were five
      times (relative risk (RR)=5.03; 95% confidence interval=1.13, 22.5) more likely
      to develop premenopausal breast cancer than those who weighed less than 3 kg (P
      value for linear trend=0.03). This corresponded to an RR of 2.31 (0.95, 5.64) per
      1 kg increase in birth weight. Birth weight was also a predictor of postnatal
      growth, that is, women who were heavy at birth remained taller and heavier
      throughout their childhood and young adulthood. However, the effect of birth
      weight on premenopausal breast cancer risk was only reduced slightly after
      simultaneous adjustment for height and body mass index (BMI) at age 2 years and
      height and BMI velocities throughout childhood and adolescence (adjusted RR=1.94
      (0.74, 5.14) per 1 kg increase in birth weight). The pathways through which birth
      weight is associated with premenopausal breast cancer risk seem to be largely
      independent of those underlying the relation of postnatal growth to risk.

PMID- 15266329
TI  - Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian
      failure on serum lipids.
AB  - In all, 146 premenopausal women with early stage breast cancer were treated with
      adjuvant chemotherapy. In addition, 5-year tamoxifen treatment was started after
      chemotherapy to those 112 patients with hormone-receptor-positive tumours while
      those with hormone-receptor-negative tumours received no further therapy. The
      serum lipid levels were followed in both groups. The levels of serum total and
      low-density lipoprotein (LDL) cholesterol increased significantly after
      chemotherapy only in patients who developed ovarian dysfunction. Total
      cholesterol increased +9.5% and LDL cholesterol +16.6% in patients who developed
      amenorrhoea (P<0.00001 and 0.00001, respectively). The cholesterol levels did not
      change in patients who preserved regular menstruation after chemotherapy. After 6
      months of tamoxifen therapy, the total cholesterol decreased -9.7% and the LDL
      cholesterol -16.7% from levels after the chemotherapy, while the cholesterol
      concentrations remained at increased levels in the control group (P=0.001 and
      P<0.0001, respectively). The high-density lipoprotein cholesterol levels did not
      change significantly in either tamoxifen or control group. The effects of
      tamoxifen treatment on serum lipids after chemotherapy have not been studied
      before. Our current study suggests that adjuvant tamoxifen therapy reverses the
      adverse effects of chemotherapy-induced ovarian failure on total and LDL
      cholesterol and even lowers their serum levels below the baseline.

PMID- 15266330
TI  - Papillary carcinoma of the thyroid: methylation is not involved in the regulation
      of MET expression.
AB  - Hypomethylation has been reported to be responsible for the activation of several
      oncogenes. The possibility that hypomethylation is involved in the regulation of
      MET transcription was investigated through the analysis of the methylation status
      of one CpG island containing 43 CpGs in six cases of papillary carcinoma, in the
      corresponding normal thyroid tissue, and in two cases of hyperplastic goitre.
      Evidence of methylation was not found in any of the analysed CpG.

PMID- 15266331
TI  - Temozolomide in paediatric high-grade glioma: a key for combination therapy?
AB  - This report describes a single-centre study with temozolomide (TMZ) (200 mg m(-2)
      day(-1) x 5 per cycle of 28 days) in children with (recurrent) high-grade glioma.
      Magnetic resonance imaging was performed every two cycles. In all, 20 patients
      were treated between 1998 and 2001 after the UKCCSG/SFOP TMZ phase II trial. All
      patients had measurable disease. Totally, 15 patients had a relapse after
      surgery+/-radiotherapy+/-chemotherapy. Overall, five patients received TMZ after
      surgery or biopsy, awaiting radiotherapy. There were one clinically malignant
      grade II glioma, 11 grade III and eight grade IV gliomas. Seven tumours had
      oligodendroglial features. Mean age at start of TMZ was 12.0 years (range 3-20.5
      years). In total, eight patients had >8 cycles (range 3-30). One VGPR (currently
      in CR after surgery), three PRs (with a PFS of 4, 4 and 11 months, respectively)
      and one MR (PFS 14 months) were observed. Three out of five responses occurred
      after >4 courses. The overall response rate was 20%. Median progression-free
      survival (PFS) was 2.0 months (range 3 weeks-34+ months). PFS rate was 20% after
      6 months. Median overall survival (OS) was 10 months. Nine patients showed a
      clinical improvement. Three patients vomitted shortly after TMZ administration,
      eight patients (13 cycles) experienced grade III/IV thrombocytopenia, occurring
      predominantly during the fourth week of the first two cycles. Five patients
      experienced neutropenia, and three patients febrile neutropenia. TMZ is a well
      tolerated ambulatory treatment for children with malignant glial tumours. This
      drug warrants further study in these highly chemoresistant tumours and should be
      studied either as upfront therapy or in combination therapy.

PMID- 15266332
TI  - The predicted effect of changes in cervical screening practice in the UK: results
      from a modelling study.
AB  - In 2003, the National Health Service Cervical Screening Programme (NHSCSP)
      announced that its screening interval would be reduced to 3 years in women aged
      25-49 and fixed at 5 years in those aged 50-64, and that women under 25 years
      will no longer be invited for screening. In order to assess these and possible
      further changes to cervical screening practice in the UK, we constructed a
      mathematical model of cervical HPV infection, cervical intraepithelial neoplasia
      and invasive cervical cancer, and of UK age-specific screening coverage rates,
      screening intervals and treatment efficacy. The predicted cumulative lifetime
      incidence of invasive cervical cancer in the UK is 1.70% in the absence of
      screening and 0.77% with pre-2003 screening practice. A reduction in lifetime
      incidence to 0.63% is predicted following the implementation of the 2003 NHSCSP
      recommendations, which represents a 63% reduction compared to incidence rates in
      the UK population if it were unscreened. The model suggests that, after the
      implementation of the 2003 recommendations, increasing the sensitivity of the
      screening test regime from its current average value of 56 to 90% would further
      reduce the cumulative lifetime incidence of invasive cervical cancer to 0.46%.
      Alternatively, extending screening to women aged 65-79 years would further reduce
      the lifetime incidence to 0.56%. Screening women aged 20-25 years would have
      minimal impact, with the cumulative lifetime incidence decreasing from 0.63 to
      0.61%. In conclusion, the study supports the 2003 recommendations for changes to
      cervical screening intervals.

PMID- 15266333
TI  - Clinical implication of expression of cyclooxygenase-2 and peroxisome
      proliferator activated-receptor gamma in epithelial ovarian tumours.
AB  - Expression of cyclooxygenase (COX)-2 plays a key role in tumorigenesis and
      development and peroxisome proliferator-activated receptor gamma (PPARgamma) has
      been implicated in the control of COX-2 expression in some tissues. The aim of
      this study is to investigate (1) whether expression of COX-2 and PPARgamma is
      associated with ovarian carcinogenesis and progression of ovarian tumours and (2)
      whether COX-2 expression is controlled through ligand-mediated activation of
      PPARgamma in ovarian carcinoma cells. For this purpose, the presence of COX-2 and
      PPARgamma was immunohistochemically examined in 71 epithelial ovarian carcinomas,
      18 borderline tumours and 23 benign tumours and the levels of COX-2 and PPARgamma
      proteins were determined by enzyme immunoassay in four benign tumours, three
      borderline tumours and 12 carcinomas. The frequency of COX-2 and PPARgamma
      detection was significantly increased and decreased as lesions progressed to
      carcinoma, respectively. The COX-2 protein was not detected in the three
      borderline tumours, whereas PPARgamma protein was detected in all of them. COX-2
      protein was detected in eight of the 12 carcinomas, whereas PPARgamma protein was
      detected in only two cases. In addition, PPARgamma protein was not detected in
      all of the eight carcinomas in which COX-2 protein was detected, suggesting that
      expression of PPARgamma and COX-2 was in a reciprocal relationship. Furthermore,
      in cultured ovarian carcinoma cells, Western blot revealed that PPARgamma and COX
      2 expression was regulated conversely as a result of stimulation by 15-deoxy
      Delta(12, 14) PGJ(2) (15-PGJ(2)), a PPARgamma activator. In addition, 15d-PGJ(2)
      suppressed tumour necrosis factor-alpha-induced-COX-2 expression, confirming the
      reciprocal correlation between COX-2 and PPARgamma. From these results, it was
      suggested that PPARgamma activation might suppress COX-2 expression via the
      nuclear factor-kappaB pathway in the ovarian carcinoma cells and that low
      expression of PPARgamma and high expression of COX-2 might be involved in
      carcinogenesis and progression of ovarian tumours.

PMID- 15266334
TI  - Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine
      alone for elderly or unfit advanced non-small-cell lung cancer patients.
AB  - The aim of this study was to assess whether a combination of gemcitabine (GEM)
      with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than
      GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC)
      patients. A total of 264 NSCLC patients aged >70 years with ECOG performance
      status (PS)< or =2, or younger with PS=2, were randomly treated with: GEM 1200 mg
      m(-2) on days 1, 8 and 15 every 28 days; PTX 100 mg m(-2) on days 1, 8 and 15
      every 28 days; GEM 1000 mg m(-2) plus PTX 80 mg m(-2) (GT) on days 1 and 8 every
      21 days; GEM 1000 mg m(-2) plus VNR 25 mg m(-2) (GV) on days 1 and 8 every 21
      days. In all arms, an intra-patients dose escalation was applied over the first
      three courses, provided that no toxicity of WHO grade > or =2 had previously
      occurred. At present time, 217 (82%) patients had died. The median (months) and 1
      year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and
      44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS< or =1
      (hazard ratio (HR)=0.67; 95% CI 0.51-0.90), and doublet treatments (HR=0.76; 95%
      CI 0.59-0.99) were significantly associated with longer survival. Doublets
      produced no more toxicity than single agents. GT should be considered a reference
      regimen for elderly NSCLC patients with PS< or =1.

PMID- 15266335
TI  - The relationship between aberrant methylation and survival in non-small-cell lung
      cancers.
AB  - The present study examined the relationship between methylation of five genes
      (p16(INK4a), RASSF1A, APC, RARbeta and CDH13) and patient survival in 351 cases
      of surgically resected lung cancers. While there was no relationship between the
      other genes and survival, p16(INK4a) methylation was significantly related to
      unfavourable prognosis in lung adenocarcinomas.

PMID- 15266336
TI  - Cancer risk before and following organ transplantation.

PMID- 15266339
TI  - A simple plan--cnidarians and the origins of developmental mechanisms.

PMID- 15266338
TI  - Metastatic seminoma treated with either single agent carboplatin or cisplatin
      based combination chemotherapy: a pooled analysis of two randomised trials.
AB  - To study the role of single agent carboplatin chemotherapy in patients with
      metastatic seminoma based on the data from two randomised trials. In subgroup
      analyses in patients with different disease characteristics, the outcome treated
      with either single agent carboplatin or cisplatin-based combination chemotherapy
      was compared. Individual patient data from two randomised European trials
      involving patients with metastatic seminoma were gathered. The primary endpoint
      for all analyses was progression-free survival. The source data of 361 patients,
      184 treated with cisplatin-based combinations and 177 treated with carboplatin
      single agent therapy, were entered into the analysis. Patient characteristics
      were comparable among the cisplatin-based and the carboplatin single agent
      treated patient groups with lymph nodes and lungs being the most frequent
      metastatic sites in 92 and 8% of patients, respectively. Overall, patients
      treated with single agent carboplatin had an inferior 5-year overall (89 and 94%;
      P=0.09) and progression-free survival rate (72 and 92%; P< 0.0001) compared with
      patients receiving cisplatin-based combinations. For all investigated subgroups
      (based on age, prior radiation therapy, metastatic sites), carboplatin single
      agent therapy was found to be inferior to cisplatin-based combination
      chemotherapy. In conclusion, carboplatin single agent therapy cannot be
      recommended as standard treatment for any patient subgroup with advanced
      metastatic seminoma and cisplatin-based combination regimens remain the standard
      of care.

PMID- 15266340
TI  - Mapping and sequencing complex genomes: let's get physical!

PMID- 15266341
TI  - Assessing the function of genetic variants in candidate gene association studies.

PMID- 15266342
TI  - Deconstructing the relationship between genetics and race.

PMID- 15266343
TI  - Genetic ancestry and the search for personalized genetic histories.

PMID- 15266344
TI  - Epistasis: too often neglected in complex trait studies?

PMID- 15266345
TI  - Thalassaemia: the long road from bedside to genome.

PMID- 15266348
TI  - M1 receptor agonism, a possible treatment for cognitive deficits in
      schizophrenia.

PMID- 15266350
TI  - Repeated administration of the GABAB receptor agonist CGP44532 decreased nicotine
      self-administration, and acute administration decreased cue-induced reinstatement
      of nicotine-seeking in rats.
AB  - Acute administration of gamma-aminobutyric acid B (GABAB) receptor agonists
      decreased nicotine, cocaine, ethanol, and heroin self-administration. GABAB
      receptor agonists also decreased cue-induced cocaine craving or seeking in humans
      and animals, respectively. The present study investigated the effects of repeated
      subcutaneous administration of the GABAB receptor agonist CGP44532 on nicotine-
      and food-maintained responding under a fixed ratio 5 schedule of reinforcement.
      The second part of the study determined whether contingent presentation of
      previously nicotine-associated cues reinstated extinguished nicotine-seeking
      behavior, and whether acute subcutaneous CGP44532 administration affected cue
      induced reinstatement of extinguished nicotine-seeking behavior. The results
      indicated that repeated administration of 0.25 mg/kg CGP44532 selectively
      decreased nicotine self-administration compared to food-maintained responding
      during the first 7 days of treatment. Repeated administration of 0.5 mg/kg/day
      CGP44532 nonselectively decreased both nicotine- and food-maintained responding.
      Contingent presentation of previously nicotine-associated cues reinstated
      extinguished nicotine-seeking behavior. Further, acute CGP44532 administration
      (0.125 and 0.25 mg/kg) decreased cue-induced reinstatement of nicotine-seeking
      behavior. In summary, the present results indicated that 0.25 mg/kg/day CGP44532
      selectively decreased nicotine self-administration compared to food-maintained
      responding, and acute administration of CGP44532 (0.125 and 0.25 mg/kg) dose
      dependently decreased cue-induced reinstatement of nicotine-seeking behavior.

PMID- 15266351
TI  - Transient plasticity of hippocampal CA1 neuron glutamate receptors contributes to
      benzodiazepine withdrawal-anxiety.
AB  - Withdrawal from 1-week oral administration of the benzodiazepine (BZ), flurazepam
      (FZP) is associated with enhanced AMPA receptor (AMPAR)-mediated and reduced NMDA
      receptor (NMDAR)-mediated excitation in CA1 pyramidal neurons 2-days after
      cessation of FZP administration. The present study examined temporal regulation
      of glutamate receptor-mediated whole-cell currents in CA1 neurons from
      hippocampal slices prepared from 0-, 1-, 2-, and 4-day FZP-withdrawn rats in
      relation to expression of anxiety-like behavior during BZ withdrawal. AMPAR
      mediated miniature excitatory postsynaptic current (mEPSC) amplitude was
      significantly increased in CA1 neurons from 1- and 2-day FZP-withdrawn rats,
      while evoked NMDAR EPSC amplitude was reduced only in neurons from 2-day FZP
      withdrawn rats. Withdrawal-anxiety, measured in the elevated plus-maze, was
      observed 1 day, but not 0, 2, or 4 days, after FZP treatment with 1-day withdrawn
      rats spending significantly reduced time in open arms compared to controls. CA1
      neuron hyperexcitability was evident from the significant increase in the
      frequency of extracellular, 4-AP-induced spike discharges in slices from 1-day
      FZP-withdrawn rats. Systemic injection of the NMDAR antagonist MK-801 (0.25
      mg/kg) on day 1 of withdrawal prevented reduced NMDAR-mediated currents in CA1
      neurons from 2-day FZP-withdrawn rats, whereas AMPAR-mediated currents remained
      upregulated. Furthermore, MK-801 'unmasked' withdrawal-anxiety in the same 2-day
      FZP-withdrawn rats. Systemic injection of the AMPAR antagonist GYKI-52466 (0.5
      mg/kg) at the onset of withdrawal blocked increased AMPAR-mediated currents and
      withdrawal-anxiety in 1-day FZP-withdrawn rats. These findings suggest that
      increased CA1 neuron AMPAR-mediated excitation may contribute to hippocampal
      hyperexcitability and expression of withdrawal-anxiety after prolonged BZ
      exposure via NMDAR-mediated neural circuits.

PMID- 15266352
TI  - Stress-induced anhedonia in mice is associated with deficits in forced swimming
      and exploration.
AB  - In order to develop a model for a depression-like syndrome in mice, we subjected
      male C57BL/6 mice to a 4-week-long chronic stress procedure, consisting of rat
      exposure, restraint stress, and tail suspension. This protocol resulted in a
      strong decrease in sucrose preference, a putative indicator of anhedonia in
      rodents. Interestingly, predisposition for stress-induced anhedonia was indicated
      by submissive behavior in a resident-intruder test. In contrast, most mice with
      nonsubmissive behavior did not develop a decrease in sucrose preference and were
      regarded as nonanhedonic. These animals were used as an internal control for
      stress-induced behavioral features not associated with the anhedonic state, since
      they were exposed to the same stressors as the anhedonic mice. Using a battery of
      behavioral tests after termination of the stress procedure, we found that
      anhedonia, but not chronic stress per se, is associated with key analogues of
      depressive symptoms, such as increased floating during forced swimming and
      decreased exploration of novelty. On the other hand, increased anxiety, altered
      locomotor activity, and loss of body weight were consequences of chronic stress,
      which occurred independently from anhedonia. Thus, behavioral correlates of
      stress-induced anhedonia and of chronic stress alone can be separated in the
      present model.

PMID- 15266353
TI  - Previous exposure to psychostimulants enhances the reinstatement of cocaine
      seeking by nucleus accumbens AMPA.
AB  - The effect of previous exposure to psychostimulants on the subsequent self
      administration of cocaine as well as reinstatement of this behavior by priming
      infusions of AMPA into the nucleus accumbens (NAcc) was examined. Rats were
      exposed to five injections, one injection every third day, of either saline or
      amphetamine (AMPH: 1.5 mg/kg, i.p.). Starting 10 days later, they were trained to
      self-administer cocaine (0.3 mg/kg/infusion, i.v.) and subsequently tested under
      a progressive ratio (PR) schedule for 4 consecutive days. As expected, rats
      exposed to AMPH worked more and obtained more cocaine infusions than saline
      exposed controls on the PR test sessions. Following daily extinction sessions
      during which saline was substituted for cocaine, the effect of priming infusions
      of AMPA (0.0, 0.08, or 0.8 nmol/0.5 microl/side) into the NAcc was then examined
      on two tests: one conducted 4 days after the last cocaine PR test session (2-3
      weeks after the last AMPH exposure injection) and the next 4 weeks later.
      Consistent with previous reports, NAcc AMPA dose-dependently reinstated cocaine
      seeking on both tests regardless of exposure condition. Importantly, this priming
      effect of NAcc AMPA was significantly enhanced in AMPH compared to saline exposed
      rats on the first test conducted 2-3 weeks after AMPH. On the second test,
      conducted 4 weeks after cocaine, reinstatement was similarly enhanced in both
      groups to levels observed on the first test in AMPH exposed rats. These results
      indicate that both noncontingent (AMPH) and contingent (cocaine) exposure to
      psychostimulants enhances the reinstatement of cocaine seeking by NAcc AMPA and
      appears to do so in a time-dependent manner.

PMID- 15266354
TI  - Assessment of radiofrequency exposure from cellular telephone daily use in an
      epidemiological study: German Validation study of the international case-control
      study of cancers of the brain--INTERPHONE-Study.
AB  - OBJECTIVE: The objective of the study is to validate self-reported cellular phone
      use information by comparing it with the cumulative emitted power and duration of
      calls measured by software-modified cellular phones (SMP). The information was
      obtained using a questionnaire developed for the international case-control study
      on the risk of the use of mobile phones in tumours of the brain or salivary gland
      (INTERPHONE-study). METHOD: The study was conducted in Bielefeld, Germany.
      Volunteers were asked to use SMPs instead of their own cellular phones for a
      period of 1 month. The SMP recorded the power emitted by the mobile phone handset
      during each base station contact. Information on cellular phone use for the same
      time period from traffic records of the network providers and from face-to-face
      interviews with the participants 3 months after the SMP use was assessed.
      Pearson's correlation coefficients and linear regression models were used to
      analyse the association between information from the interview and from the SMP.
      RESULTS: In total, 1757 personal mobile phone calls were recorded for 45 persons
      by SMP and traffic records. The correlation between the self-reported information
      about the number and the duration of calls with the cumulative power of calls was
      0.50 (P<0.01) and 0.48 (P<0.01), respectively. Almost 23% of the variance of the
      cumulative power was explained by either the number or the cumulative duration of
      calls. After inclusion of possible confounding factors in the regression model,
      the variance increased to 26%. Minor confounding factors were "network provider",
      "contract form", and "cellular phone model". DISCUSSION: The number of calls
      alone is a sufficient parameter to estimate the cumulative power emitted by the
      handset of a cellular telephone. The cumulative power emitted by these phones is
      only associated with number of calls but not with possible confounding factors.
      Using the mobile phone while driving, mainly in cities, or mainly in rural areas
      is not associated with the recorded cumulative power in the SMP.

PMID- 15266355
TI  - Beyond user fees.

PMID- 15266356
TI  - Population rates of hospitalization for atrial fibrillation/flutter in Canada.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most prevalent sustained cardiac
      dysrhythmia and constitutes a major public health problem. AF significantly
      increases the risk of stroke, and anticoagulation has been shown to reduce this
      risk. However, Canadian data on the prevalence of AF and the use of warfarin in
      these patients are lacking. METHODS: International Classification of Diseases,
      ninth revision, codes for admissions to acute care hospitals in Canada were used
      to estimate the prevalence of hospitalization for AF between 1997/1998 and
      1999/2000, and subsequent readmissions for stroke in all 10 provinces and overall
      in Canada. Warfarin use was obtained by linkage with drug benefit plans in
      Alberta, British Columbia, Nova Scotia and Ontario, for patients 65 years and
      older. RESULTS: The overall rate of hospitalization with AF between April 1,
      1997, and March 31, 2000, was 582.7 per 100,000 population. The age- and sex
      standardized rate rose from 513.4 to 555.3 during the three-year period of
      observation. The mean age was 74.4 years and 51.8% of patients were male. Of
      those discharged alive, 2.7% were readmitted for stroke within one year. Overall,
      less than one-half of the patients with AF filled a prescription for warfarin
      within 90 days of discharge, with only a small increase in warfarin use over the
      study time period. CONCLUSIONS: The rate of hospitalization with AF is increasing
      in Canada and is more frequent in men than in women across all age groups.
      Consistent with reports from other countries, warfarin use was lower than one
      might expect given its efficacy, with only a small increase in use over time.

PMID- 15266357
TI  - Parental preference regarding hospitals for children undergoing surgery: a trade
      off between travel distance and potential outcome improvement.
AB  - OBJECTIVE: To explore parental preference in the choice between a local and a
      referral hospital for children undergoing heart surgery. METHODS: One hundred
      three parents or adult primary caregivers of children referred to a pediatric
      cardiology clinic were interviewed. Participants were presented with hypothetical
      scenarios in which they or their children had a heart condition requiring
      elective surgery. The surgery could be performed at either a local hospital or a
      regional referral hospital. The travel time to the referral hospital was
      initially presented as 2 h, and the mortality rate was set at 3% for both the
      local and the referral hospitals. The parents were then presented with scenarios
      that sequentially increased the mortality of the local hospital and the distance
      to the referral hospital, and were asked to choose between the local and regional
      referral hospitals. RESULTS: When the regional referral hospital was 2 h away and
      the mortality rates for the referral hospital and the local hospital were equal
      at 3%, 82.5% of participants chose the local hospital for their children. The
      percentage of participants choosing the local hospital decreased progressively as
      the mortality rate of the local hospital increased (to 9.7% at 18% mortality).
      Between 5% and 10% more participants chose the local hospital when the distance
      to the referral hospital was increased from 2 h to 4 h. There was no difference
      in age, sex, ethnicity, language, type of insurance, level of education and
      availability of personal transportation between participants who chose the
      regional referral hospital and those who chose the local hospital. Participants
      who lived closer to the hospital at which the survey was conducted were more
      likely to choose the local hospital. CONCLUSION: The present study defines a
      relation between potential outcome improvement and increasing travel distance
      from a patient or parent's perspective. This trade-off is an important
      consideration when planning for regionalization.

PMID- 15266358
TI  - Measurement of continuity of care in cardiac patients: reliability and validity
      of an in-person questionnaire.
AB  - BACKGROUND: Breaks in continuity of care occur during the care of patients with
      cardiac conditions, such as congestive heart failure (CHF) and atrial
      fibrillation (AF), during their hospitalization, the discharge process or follow
      up care. Recently, to measure continuity of care for such patients, a
      comprehensive questionnaire was developed to reflect the cardiac patient's
      perspective on multifaceted aspects of continuity of care. OBJECTIVE: To examine
      the psychometric properties of an in-person interview questionnaire for the
      measurement of continuity of care in patients recently hospitalized with CHF or
      AF. METHODS: The Heart Continuity of Care Questionnaire (HCCQ) was administered
      to 350 cardiac patients (176 with CHF and 174 with AF) at least six months after
      discharge from hospitals in two urban centres. The questionnaire was assessed by
      item and principal components analysis. Factors derived from principal components
      analysis were assessed for internal consistency and construct validity against
      variables of comorbidity, health status and symptom severity. RESULTS: A
      principal components analysis produced three subscales. These subscales were
      internally consistent, and demonstrated construct validity through expected
      correlations with other variables and theoretical constructs. CONCLUSION: The
      present study supports the reliability and validity of the HCCQ for measuring
      continuity of care. The HCCQ subscales correspond to the theoretical components
      of continuity of care that have been proposed, namely relational, informational
      and management continuity. The HCCQ subscales may be of value for identifying
      problems in continuity of care and for evaluating interventions aimed at
      improving continuity of care for cardiac patients after hospital discharge.

PMID- 15266359
TI  - Cardiovascular response to exercise in elite ice hockey players.
AB  - BACKGROUND: High-performance ice hockey requires unique strength and endurance,
      which are facilitated by training. OBJECTIVES: To investigate the cardiovascular
      response to training and competition at rest and during recumbent bicycle
      echocardiography Doppler exercise in 26 elite ice hockey players, and to compare
      the results with those of 14 healthy, active, young male student volunteers.
      METHODS: Two-dimensional echocardiography Doppler was applied to determine
      cardiac chamber size and wall thickness, and to estimate rest and exercise
      tricuspid regurgitation peak velocity (TRV), stroke volume (SV) and cardiac
      output. RESULTS: The left atrium, interventricular septal thickness, and left
      ventricular end-systolic and end-diastolic diameters and volumes were larger in
      athletes. During exercise, the systolic and diastolic blood pressure increments
      were similar in the athletes and the control subjects, but the increase in heart
      rate (HR) per stage was greater in the control subjects. TRV was higher in the
      athletes and increased at each step to 240 W, while the TRV in the control group
      began to decline at 160 W. The cardiac output increased with each stage in both
      groups, but was determined by the increment of SV and HR in the athletes, and
      primarily by HR in the control subjects. CONCLUSIONS: Myocardial adaptation for
      elite ice hockey players is characterized by increased chamber size and wall
      thickness typical of combined endurance and sprint sports. The systemic blood
      pressure response to exercise is similar in athletes and nonathletes. The higher
      TRV at rest and at each level of exercise appears to be related to the higher SV,
      an expression of a physiological phenomenon.

PMID- 15266360
TI  - Absence of sex differences in pharmacotherapy for acute myocardial infarction.
AB  - BACKGROUND: Previous studies have indicated that sex differences may exist in the
      pharmacological management of acute myocardial infarction (AMI), with female
      patients being treated less aggressively. OBJECTIVES: To determine if previously
      reported sex differences in AMI medication use were also evident among all AMI
      patients treated at hospitals in an urban Canadian city. METHODS: All patients
      who had a primary discharge diagnosis of AMI from all three adult care hospitals
      in Calgary, Alberta, in the 1998/1999 fiscal year were identified from hospital
      administrative records (n=914). A standardized, detailed chart review was
      conducted. Information collected from the medical charts included
      sociodemographic and clinical characteristics, comorbid conditions, and
      cardiovascular medication use during hospitalization and at discharge. RESULTS:
      Similar proportions of female and male patients were treated with thrombolytics,
      beta-blockers, angiotensin-converting enzyme inhibitors, nitrate, heparin,
      diuretics and digoxin. Among patients aged 75 years and over, a smaller
      proportion of female patients received acetylsalicylic acid in hospital than did
      male patients (87% versus 95%; P=0.026). Multivariable logistic regression
      analysis revealed that, after correction for age, use of other
      anticoagulants/antiplatelets and death within 24 h of admission, sex was no
      longer an independent predictor for receipt of acetylsalicylic acid in hospital.
      Medications prescribed at discharge were similar between male and female
      patients. CONCLUSION: The results from this Canadian chart review study, derived
      from detailed clinical data, indicate that the pattern of pharmacological
      treatment of female and male AMI patients during hospitalization and at discharge
      was very similar. No sex differences were evident in the treatment of AMI among
      patients treated in an urban Canadian centre.

PMID- 15266361
TI  - Robotically assisted endoscopic transmyocardial laser revascularization.
AB  - BACKGROUND: The surgical approach to transmyocardial laser revascularization
      (TMR) via thoracotomy has been approved for the treatment of angina in inoperable
      patients, but it has had limited use as a stand-alone procedure. OBJECTIVES: To
      assess the feasibility and efficacy of robotically assisted endoscopic TMR using
      the Zeus robotic surgical system (Computer Motion, USA) and an excimer TMR system
      (Spectranetics, USA) in a porcine model. METHODS: Five pigs weighing 20 kg to 40
      kg were used. A 10 mm endoscope, two 5 mm instrument ports and a 1.4 mm TMR probe
      were introduced into the left hemithorax. Endoscopic TMR was performed on the
      anterolateral or lateral left ventricular wall using Zeus instruments to hold and
      guide the TMR probe. RESULTS: The mean system set-up time was 4.2+/-0.6 min, the
      mean port placement time was 11+/-1.7 min, the mean TMR procedure time was 5.0+/
      0.7 min and the mean number of transmural TMR channels was 10+/-3.6. All pigs
      tolerated the entire procedure. Histological examination showed that transmural
      channels were successfully created. CONCLUSIONS: Endoscopic TMR using the Zeus
      system was feasible, in a pig model, in creating transmural laser channels on the
      anterior and lateral left ventricle, and may provide a significant advantage over
      the open chest approach in reducing perioperative morbidity and improving
      recovery.

PMID- 15266362
TI  - Hypersensitivity myocarditis complicating hypertrophic cardiomyopathy heart.
AB  - The present report describes a case of eosinophilic myocarditis complicating
      hypertrophic cardiomyopathy. The 47-year-old female patient, known to have
      hypertrophic cardiomyopathy, was admitted with biventricular failure and managed
      aggressively with dobutamine infusion and other drugs while being assessed for
      heart transplantation. On transthoracic echocardiogram, she had moderate left
      ventricular dysfunction with regional variability and moderate mitral
      regurgitation. The recipient's heart showed the features of apical hypertrophic
      cardiomyopathy and myocarditis with abundant eosinophils. Myocarditis is rare and
      eosinophilic myocarditis is rarer. It is likely that the hypersensitivity
      (eosinophilic) myocarditis was related to dobutamine infusion therapy.
      Eosinophilic myocarditis has been reported with an incidence of 2.4% to 7.2% in
      explanted hearts and may be related to multidrug therapy.

PMID- 15266363
TI  - Embolic myocardial infarction in a pregnant woman with a mechanical heart valve
      on low molecular weight heparin.
AB  - Even with continuing technical improvements in prosthesis design and the
      development of less thrombogenic materials, mechanical valve prostheses still
      carry a thromboembolic risk significant enough to warrant long-term
      anticoagulation therapy. Optimal anticoagulation is especially crucial during
      pregnancy due to the hypercoagulable state that rapidly develops after
      conception. Conventional anticoagulation therapy with coumarin derivatives is
      associated with risks of teratogenicity and hemorrhage for the fetus, and
      thromboembolic and hemorrhagic complications for the mother. As a result, other
      forms of anticoagulation, such as unfractionated or low molecular weight heparin,
      have been advocated as an alternative in selected cases. The present report
      describes a case of embolic myocardial infarction occurring in a pregnant woman
      with an aortic bileaflet mechanical valve prosthesis while on therapeutic low
      molecular weight heparin after only one dose was withheld before amniocentesis.

PMID- 15266364
TI  - Images in cardiology: Unruptured right sinus of Valsalva aneurysm.

PMID- 15266366
TI  - Mobile gene cassettes: a fundamental resource for bacterial evolution.
AB  - Horizontal gene transfer increases genetic diversity in prokaryotes to a degree
      not allowed by the limitations of reproduction by binary fission. The
      integron/gene cassette system is one of the most recently characterized examples
      of a system that facilitates horizontal gene transfer. This system, discovered in
      the context of multidrug resistance, is recognized in a clinical context for its
      role in allowing pathogens to adapt to the widespread use of antibiotics. Recent
      studies suggest that gene cassettes are common and encode functions relevant to
      many adaptive traits. To estimate the diversity of mobile cassettes in a natural
      environment, a molecular technique was developed to provide representative
      distributions of cassette populations at points within a sampling area.
      Subsequently, statistical methods analogous to those used for calculating species
      diversity were employed to assess the diversity of gene cassettes within the
      sample area in addition to gaining an estimate of cassette pool size. Results
      indicated that the number of cassettes within a 5x10-m sample area was large and
      that the overall mobile cassette metagenome was likely to be orders of magnitude
      larger again. Accordingly, gene cassettes appear to be capable of mobilizing a
      significant genetic resource and consequently have a substantial impact on
      bacterial adaptability.

PMID- 15266367
TI  - Selection, inheritance, and the evolution of parent-offspring interactions.
AB  - Very few studies have examined parent-offspring interactions from a quantitative
      genetic perspective. We used a cross-fostering design and measured genetic
      correlations and components of social selection arising from two parental and two
      offspring behaviors in the burying beetle Nicrophorus vespilloides. Genetic
      correlations were assessed by examining behavior of relatives independent of
      common social influences. We found positive genetic correlations between all
      pairs of behaviors, including between parent and offspring behaviors. Patterns of
      selection were assessed by standardized performance and selection gradients.
      Parental provisioning had positive effects on offspring performance and fitness,
      while remaining near the larvae without feeding them had negative effects.
      Begging had positive effects on offspring performance and fitness, while
      increased competition among siblings had negative effects. Coadaptations between
      parenting and offspring behavior appear to be maintained by genetic correlations
      and functional trade-offs; parents that feed their offspring more also spend more
      time in the area where they can forage for themselves. Families with high levels
      of begging have high levels of sibling competition. Integrating information from
      genetics and selection thus provides a general explanation for why variation
      persists in seemingly beneficial traits expressed in parent-offspring
      interactions and illustrates why it is important to measure functionally related
      suites of behaviors.

PMID- 15266368
TI  - Lost in time, lonely, and single: reproductive asynchrony and the Allee effect.
AB  - Identifying linkages between life-history traits and small population processes
      is essential to effective multispecies conservation. Reproductive asynchrony,
      which occurs when individuals are reproductively active for only a portion of the
      population-level breeding period, may provide one such link. Traditionally,
      reproductive asynchrony has been considered from evolutionary perspectives as an
      advantageous bet-hedging strategy in temporally unpredictable environments. Here,
      we explore the dynamic consequences of reproductive asynchrony as a density
      dependent life-history trait. To examine how asynchrony affects population growth
      rate and extinction risk, we used a general model of reproductive timing to
      quantify the temporal overlap of opposite-sex individuals and to simulate
      population dynamics over a range of initial densities and empirical estimates of
      reproductive asynchrony. We also considered how protandry, a sexually selected
      life-history strategy that often accompanies asynchrony, modulates the population
      level effects of reproductive asynchrony. We found that asynchrony decreases the
      number of males a female overlaps with, decreases the average probability of
      mating per male/female pair that does overlap, and leaves some females completely
      isolated in time. This loss of reproductive potential, which is exacerbated by
      protandry, reduces population growth rate at low density and can lead to
      extinction via an Allee effect. Thus reproductive asynchrony and protandry, both
      of which can be evolutionarily advantageous at higher population densities, may
      prove detrimental when population density declines.

PMID- 15266369
TI  - Constraints on adaptive evolution: the functional trade-off between reproduction
      and fast-start swimming performance in the Trinidadian guppy (Poecilia
      reticulata).
AB  - The empirical study of natural selection reveals that adaptations often involve
      trade-offs between competing functions. Because natural selection acts on whole
      organisms rather than isolated traits, adaptive evolution may be constrained by
      the interaction between traits that are functionally integrated. Yet, few
      attempts have been made to characterize how and when such constraints are
      manifested or whether they limit the adaptive divergence of populations. Here we
      examine the consequences of adaptive life-history evolution on locomotor
      performance in the live-bearing guppy. In response to increased predation from
      piscivorous fish, Trinidadian guppies evolve an increased allocation of resources
      toward reproduction. These populations are also under strong selection for rapid
      fast-start swimming performance to evade predators. Because embryo development
      increases a female's wet mass as she approaches parturition, an increased
      investment in reproductive allocation should impede fast-start performance. We
      find evidence for adaptive but constrained evolution of fast-start swimming
      performance in laboratory trials conducted on second-generation lab-reared fish.
      Female guppies from high-predation localities attain a faster acceleration and
      velocity and travel a greater distance during fast-start swimming trials.
      However, velocity and distance traveled decline more rapidly over the course of
      pregnancy in these same females, thus reducing the magnitude of divergence in
      swimming performance between high- and low-predation populations. This functional
      trade-off between reproduction and swimming performance reveals how different
      aspects of the phenotype are integrated and highlights the complexity of
      adaptation at the whole-organism level.

PMID- 15266370
TI  - Trade-offs between immune investment and sexual signaling in male mallards.
AB  - Allocation trade-offs between the immune system and sexual traits are central to
      current sexual selection hypotheses but remain contentious. Such trade-offs could
      be brought about by the dual action of testosterone that stimulates sexual
      signals but also suppresses immune functions and/or by competition for
      carotenoids that can be deposited in ornaments or used as antioxidants in support
      of immune functions. We investigated the trade-off between investment in immunity
      and maintenance of testosterone, carotenoids, and sexually selected, carotenoid
      based bill color in male mallards. Following a nonpathogenic immune challenge,
      facultative immune investment resulted in a syndrome of changes in allocation.
      Plasma carotenoids disappeared from circulation proportional to antibody
      production. In addition, the reflectance spectrum of the bill was affected;
      greater antibody production was associated with an increase in relative UV
      reflectance. Although changes in bill reflectance and plasma carotenoids were
      related, the relationship appeared more complex than direct competition with
      immunity. Finally, maintenance of testosterone was affected by immune investment:
      testosterone levels declined substantially when males produced more antibodies.
      Because males with high testosterone are preferred by females, the decline in
      testosterone, in addition to carotenoid depletion and effects on bill
      reflectance, could constitute a significant cost of immune investment.

PMID- 15266371
TI  - Age-specific demography in Plantago: uncovering age-dependent mortality in a
      natural population.
AB  - Accurate measures of age-dependent mortality are critical to life-history
      analysis and measures of fitness, yet these measures are difficult to obtain in
      natural populations. Age-dependent mortality patterns can be obscured not only by
      seasonal variation in environmental conditions and reproduction but also by
      changes in the heterogeneity among individuals in the population over time due to
      selection. This study of Plantago lanceolata uses longitudinal data from a field
      study with a large number of individuals to develop a model to estimate the shape
      of the baseline hazard function that represents the age-dependent risk of
      mortality. The model developed here uses both constant (genetics, spatial
      location) and time-varying (temperature, rainfall, reproduction, size) covariates
      not only to estimate the underlying mortality pattern but also to demonstrate
      that the risk of mortality associated with fitness components can change with
      time/age. Moreover, this analysis suggests that increasing size after
      reproductive maturity may allow this plant species to escape from demographic
      senescence.

PMID- 15266372
TI  - The maintenance (or not) of polygenic variation by soft selection in
      heterogeneous environments.
AB  - On the basis of single-locus models, spatial heterogeneity of the environment
      coupled with strong population regulation within each habitat (soft selection) is
      considered an important mechanism maintaining genetic variation. We studied the
      capacity of soft selection to maintain polygenic variation for a trait determined
      by several additive loci, selected in opposite directions in two habitats
      connected by dispersal. We found three main types of stable equilibria. Extreme
      equilibria are characterized by extreme specialization to one habitat and loss of
      polymorphism. They are analogous to monomorphic equilibria in singe-locus models
      and are favored by similar factors: high dispersal, weak selection, and low
      marginal average fitness of intermediate genotypes. At the remaining two types of
      equilibria the population mean is intermediate but variance is very different. At
      fully polymorphic equilibria all loci are polymorphic, whereas at low-variance
      equilibria at most one locus remains polymorphic. For most parameters only one
      type of equilibrium is stable; the transition between the domains of fully
      polymorphic and low-variance equilibria is typically sharp. Low-variance
      equilibria are favored by high marginal average fitness of intermediate
      genotypes, in contrast to single-locus models, in which marginal overdominance is
      particularly favorable for maintenance of polymorphism. The capacity of soft
      selection to maintain polygenic variation is thus more limited than extrapolation
      from single-locus models would suggest, in particular if dispersal is high and
      selection weak. This is because in a polygenic model, variance can evolve
      independently of the mean, whereas in the single-locus two-allele case, selection
      for an intermediate mean automatically leads to maintenance of polymorphism.

PMID- 15266373
TI  - Dynamics of compartmented and reticulate food webs in relation to energetic
      flows.
AB  - Using simple food webs, we address how the interactions of food web structure and
      energetic flows influence dynamics. We examine the effect of food web topologies
      with equivalent energetics (i.e., trophic interactions are equivalent at each
      trophic level), following which we vary energetic flows to include weak and
      strong interactions or nonequivalent energetics. In contrast to some work (Pimm
      1979), we find that compartmented webs are more stable than reticulate webs.
      However, we find that nonequivalent energetics can stabilize previously unstable
      reticulate structures. It is not only weak flows that can be stabilizing but also
      the arrangement of the flows that emphasizes stabilizing mechanisms. We find that
      the main stabilizing mechanism is asynchrony, where structures and energetic
      arrangements that decrease synchrony such as internal segregation or competition
      will stabilize dynamics. Since compartments allow prey dynamics to behave
      somewhat independently, compartmentation readily promotes stability. In addition,
      these results can be scaled from simple food webs to more complex webs with many
      interacting subsystems so that linking weak subsystems to strong ones can
      stabilize dynamics. We show that food web dynamics are determined not only by
      topology but also the arrangement of weak and strong energetic flows.

PMID- 15266374
TI  - Triploid bridge and role of parthenogenesis in the evolution of autopolyploidy.
AB  - Autopolyploidization is considered to play an important role in plant evolution.
      In polyploidization, the polyploid evolves from the original diploid cytotype, in
      which the triploid state is considered to mediate the process (triploid bridge).
      Nevertheless, the fitness of triploid individuals seems to be too low to
      facilitate the polyploidization process (triploid block). The evolutionary
      condition of autopolyploidy was analyzed using a mathematical model focusing on
      the role of parthenogenesis in triploid and tetraploid individuals. In addition,
      offspring were assumed to arise by sexual reproduction by conjugations between
      haploid, diploid, and triploid gametes produced by diploid, tetraploid, and
      triploid individuals. According to the analysis, even if triploid block
      suppresses the fitness of sexually produced triploids, the polyploidization
      process can proceed when parthenogenesis occurs frequently. If only triploids
      frequently reproduce parthenogenetically, the evolutionary consequences tend to
      depend on the fitness of the tetraploid individuals. On the basis of a
      predetermined parameter set, if tetraploid fitness is relatively low, all three
      ploidies can coexist. Otherwise, tetraploidization occurs. In this case, triploid
      parthenogenesis promotes not only triploidization but also tetraploidization.
      However, if both triploids and tetraploids frequently reproduce
      parthenogenetically, the ploidy levels with the highest fitness are likely to
      dominate in the population through direct competition among cytotypes.

PMID- 15266375
TI  - Plant defense and density dependence in the population growth of herbivores.
AB  - Long-standing theory has predicted that plant defensive and nutritional traits
      contribute to the population dynamics of insect herbivores. To examine the role
      of plant variation in density dependence, I took a comparative approach by
      conducting density manipulation experiments with the specialist aphid, Aphis
      nerii, on 18 species of milkweed (Asclepias spp.). The strength of density
      dependence varied on the plant species. Variation in plant secondary compounds
      (cardenolides), trichomes, leaf carbon and nitrogen concentrations, and seed mass
      of the milkweed species predicted the R(max) of aphid populations, while specific
      leaf weight, carbon concentration, latex, water content, and trichome density
      were significant predictors of the strength of density dependence. Thus, plant
      traits that probably evolved for primary and defensive functions contribute to
      the ecological dynamics of herbivore populations.

PMID- 15266376
TI  - The latitudinal gradient in niche breadth: concepts and evidence.
AB  - We examine Robert MacArthur's hypothesis that niche breadth is positively
      associated with latitude (the latitude-niche breadth hypothesis). This idea has
      been influential and long standing, yet no studies have evaluated its generality
      or the validity of its assumptions. We review the theoretical arguments
      suggesting a positive relationship between niche breadth and latitude. We also
      use available evidence to evaluate the assumptions and predictions of MacArthur's
      latitude-niche breadth hypothesis. We find that neither the assumptions nor the
      predictions of the hypothesis are supported by data. We propose an alternative
      hypothesis linking latitude with niche breadth. Unlike previous ideas, our
      conceptual framework does not require equilibrial assumptions and is based on
      recently uncovered patterns of species interactions.

PMID- 15266377
TI  - Affording larger brains: testing hypotheses of mammalian brain evolution on bats.
AB  - Several major hypotheses have been proposed to explain how larger brains in
      mammals, such as those of humans, are afforded in energetic terms. To date, these
      have been largely tested on primates, with some cross-mammal analysis. We use
      morphological, ecological, and metabolic data for 313 species of bats to examine
      the allometry of brain mass and to test key predictions from three of these
      hypotheses: the direct metabolic constraint, expensive tissue, and maternal
      energy hypotheses. We confirm that megachiropteran bats (entirely fruit-eating)
      have larger brains for their body mass than microchiropteran bats (fruit-eating
      and non-fruit-eating) and fruit-eating species (Megachiroptera and
      Microchiroptera) have larger brains than non-fruit-eating species
      (Microchiroptera). Although our analyses demonstrate little or no support for any
      of the three hypotheses, we show that 95.9% of the variance in brain mass can be
      explained by the independent effects of gestation length and body mass. This
      indicates that among bats, the duration of maternal investment plays an important
      role in the adult brain mass finally obtained. These analyses serve to emphasis
      the crucial importance of testing the general applicability of macroevolutionary
      hypotheses (often developed in isolation in one clade) in multiple clades with
      different evolutionary histories.

PMID- 15266378
TI  - Community ecology: is it time to move on? (An American Society of Naturalists
      presidential address).
AB  - Because of the contingency and complexity of its subject matter, community
      ecology has few general laws. Laws and models in community ecology are highly
      contingent, and their domain is usually very local. This fact does not mean that
      community ecology is a weak science; in fact, it is the locus of exciting
      advances, with growing mechanistic understanding of causes, patterns, and
      processes. Further, traditional community ecological research, often local,
      experimental, and reductionist, is crucial in understanding and responding to
      many environmental problems, including those posed by global changes. For both
      scientific and societal reasons, it is not time to abandon community ecology.

PMID- 15266379
TI  - Pleiotropy and the genomic location of sexually selected genes.
AB  - Sexual selection drives the evolution of traits involved in the competition for
      mates. Although considerable research has focused on the evolution of sexually
      selected traits, their underlying genetic architecture is poorly resolved. Here I
      address the pleiotropic effects and genomic locations of sexually selected genes.
      These two important characteristics can impose considerable constraints on
      evolvability and may influence our understanding of the process of sexual
      selection. Theoretical models are inconsistent regarding the genomic location of
      sexually selected genes. Models that do not incorporate pleiotropic effects often
      predict sex linkage. Conversely, sex linkage is not explicitly predicted by the
      condition-dependent model (which considers pleiotropic effects). Evidence largely
      based on reciprocal crosses supports the notion of sex linkage. However, although
      they infer genetic contribution, reciprocal crosses cannot identify the genes or
      their pleiotropic effects. By surveying the genome of Drosophila melanogaster, I
      provide evidence for the genomic location and pleiotropic effects of 63
      putatively sexually selected genes. Interestingly, most are pleiotropic (73%),
      and they are not preferentially sex linked. Their pleiotropic effects include
      fertility, development, life span, and viability, which may contribute to
      condition and/or fitness. My findings may also provide evidence for the capture
      of genetic variation in condition via the pleiotropic effects of sexually
      selected genes.

PMID- 15266380
TI  - Parallel evolution and inheritance of quantitative traits.
AB  - Parallel phenotypic evolution, the independent evolution of the same trait in
      closely related lineages, is interesting because it tells us about the
      contribution of natural selection to phenotypic evolution. Haldane and others
      have proposed that parallel evolution also results from a second process, the
      similarly biased production of genetic variation in close relatives, an idea that
      has received few tests. We suggest that influence of shared genetic biases should
      be detectable by the disproportionate use of the same genes in independent
      instances of parallel phenotypic evolution. We show how progress in testing this
      prediction can be made through simple tests of parallel inheritance of genetic
      differences: similar additive, dominance, and epistasis components in analysis of
      line means and similar effective numbers of loci. We demonstrate parallel
      inheritance in two traits, lateral plate number and body shape, in two lineages
      of threespine stickleback that have adapted independently to freshwater streams
      on opposite sides of the Pacific Ocean. Notably, reduction of plate number in
      freshwater involves a substitution at the same major locus in both lineages. Our
      results represent only a first step in the study of the genetics of parallel
      phenotypic evolution in sticklebacks. Nevertheless, we have shown how such
      studies can be employed to test the genetic hypothesis of parallel evolution and
      how study of parallel evolution might yield insights into the roles of both
      selection and genetic constraint in phenotypic evolution.

PMID- 15266381
TI  - Phylogenetic overdispersion in Floridian oak communities.
AB  - Closely related species that occur together in communities and experience similar
      environmental conditions are likely to share phenotypic traits because of the
      process of environmental filtering. At the same time, species that are too
      similar are unlikely to co-occur because of competitive exclusion. In an effort
      to explain the coexistence of 17 oak species within forest communities in North
      Central Florida, we examined correlations between the phylogenetic relatedness of
      oak species, their degree of co-occurrence within communities and niche overlap
      across environmental gradients, and their similarity in ecophysiological and life
      history traits. We show that the oaks are phylogenetically overdispersed because
      co-occurring species are more distantly related than expected by chance, and oaks
      within the same clade show less niche overlap than expected. Hence, communities
      are more likely to include members of both the red oak and the white + live oak
      clades than only members of one clade. This pattern of phylogenetic
      overdispersion arises because traits important for habitat specialization show
      evolutionary convergence. We hypothesize further that certain conserved traits
      permit coexistence of distantly related congeners. These results provide an
      explanation for how oak diversity is maintained at the community level in North
      Central Florida.

PMID- 15266382
TI  - The evolution of jumping performance in Caribbean Anolis lizards: solutions to
      biomechanical trade-offs.
AB  - Adaptationist theory predicts that species will evolve functional specializations
      for occupying different ecological niches. However, whereas performance traits
      are often complex, most comparative functional studies examine only simple
      measures of performance (e.g., sprint speed). Here we examine multiple facets of
      jumping biomechanics in 12 species of Caribbean Anolis lizards. These 12 species
      represent six ecomorphs, which are distinct ecological and morphological entities
      that have independently evolved on different Caribbean islands. We first show
      that the optimal angles for jumping maximum horizontal distances range from 39
      degrees to 42 degrees, but the average jump angle of the 12 species is about 36
      degrees. Interestingly, these "suboptimal" jumping angles result in only a small
      decrement in jump distance but substantial savings in flight duration and jump
      height. Further, our data show that the two key variables associated with
      increased jumping velocity (hindlimb length and takeoff acceleration) are
      independent of one another. Thus, there are two possible ways to achieve superior
      jumping capabilities: to evolve more muscular limbs--as stronger legs will
      produce more force and, hence, more acceleration--or evolve longer limbs. Our
      data show that anole species face trade-offs that prevent them from
      simultaneously optimizing different aspects of jumping ability but that they
      appear to have evolved behaviors that partially overcome these trade-offs.

PMID- 15266383
TI  - Coupled oscillations in food webs: balancing competition and mutualism in simple
      ecological models.
AB  - As in other oscillating systems, oscillations of consumer resource pairs in
      ecological systems may be coupled such that complex behavior results. The form of
      that coupling may determine the nature and extent of this behavior. Two
      biologically significant forms of coupling are here investigated: first, where
      consumers consume each other's resources (CR coupling, representing competition
      between the two consumers), and second, where the resources are in competition
      with one another (RR coupling, potentially representing indirect mutualism
      between the two consumers). Interestingly, CR coupling leads to in-phase
      synchrony of the oscillations, whereas RR coupling leads to antiphase synchrony.
      With either form of coupling, if the coupling remains weak, synchronous behavior
      is generated in the two systems. At strong levels of coupling, when the two forms
      act simultaneously, a balance between competition and mutualism is generated,
      which is manifest differently at different levels of resource coupling.

PMID- 15266384
TI  - Evolution of morphological integration. I. Functional units channel stress
      induced variation in shrew mandibles.
AB  - Stress-induced deviations from normal development are often assumed to be random,
      yet their accumulation and expression can be influenced by patterns of
      morphological integration within an organism. We studied within-individual
      developmental variation (fluctuating asymmetry) in the mandible of four shrew
      species raised under normal and extreme environments. Patterns of among
      individual variation and fluctuating asymmetry were strongly concordant in traits
      that were involved in the attachment of the same muscles (i.e., functionally
      integrated traits), and fluctuating asymmetry was closely integrated among these
      traits, implying direct developmental interactions among traits involved in the
      same function. Stress-induced variation was largely confined to the directions
      delimited by functionally integrated groups of traits in the pattern that was
      concordant with species divergence--species differed most in the same traits that
      were most sensitive to stress within each species. These results reveal a strong
      effect of functional complexes on directing and incorporating stress-induced
      variation during development and might explain the historical persistence of sets
      of traits involved in the same function in shrew jaws despite their high
      sensitivity to environmental variation.

PMID- 15266385
TI  - Testing small clutch size models with Daphnia.
AB  - Life-history theory predicts that for small clutches, variance in egg size
      (between individuals) should decrease in a predictable invariant manner as clutch
      size increases. To test this, we studied Daphnia magna at 350 different food
      treatments and recorded the number of eggs and the volume of each egg for their
      first clutch. As predicted, we found that the relationship between clutch size
      and resources devoted to reproduction was linear, variance in egg volume
      decreased with increasing clutch size, and resources were shared relatively
      equally between the eggs in a clutch. However, we found that the rate at which
      the range of egg volumes decreased with clutch size was slower than predicted. We
      discuss possible explanations for this discrepancy, including a lower limit on
      the volume of eggs that are produced and selection for smaller eggs when food is
      abundant. Consistent with this, we found that mean egg volume decreased with
      increasing clutch size.

PMID- 15266386
TI  - The ecological genetics of conditional strategies.
AB  - We develop a quantitative genetic model for conditional strategies that
      incorporates the ecological realism of previous strategic models. Similar to
      strategic models, the results show that environmental heterogeneity, cue
      reliability, and environment-dependent fitness trade-offs for the alternative
      tactics of the conditional strategy interact to determine when conditional
      strategies will be favored and that conditional strategies should be a common
      form of adaptive variation in nature. The results also show that conditional and
      unconditional development can be maintained in one of two ways: by frequency
      dependent selection or by the maintenance of genetic variation that exceeds the
      threshold for induction. We then modified the model to take into account variance
      in exposures to the environmental cue as well as variance in response to the cue,
      which allows a derivation of a dose-response curve. Here the results showed that
      increasing the genetic variance for response both flattens and shifts the dose
      response curve. Finally, we modify the model to derive the dose-response curve
      for a population polymorphic for a gene that blocks expression of the conditional
      strategy. We illustrate the utility of the model by application to predator
      induced defense in an intertidal barnacle and compare the results with phenotypic
      models of selection.

PMID- 15266387
TI  - Disentangling extrinsic from intrinsic factors in disease dynamics: a nonlinear
      time series approach with an application to cholera.
AB  - Alternative explanations for disease and other population cycles typically
      include extrinsic environmental drivers, such as climate variability, and
      intrinsic nonlinear dynamics resulting from feedbacks within the system, such as
      species interactions and density dependence. Because these different factors can
      interact in nonlinear systems and can give rise to oscillations whose frequencies
      differ from those of extrinsic drivers, it is difficult to identify their
      respective contributions from temporal population patterns. In the case of
      disease, immunity is an important intrinsic factor. However, for many diseases,
      such as cholera, for which immunity is temporary, the duration and decay pattern
      of immunity is not well known. We present a nonlinear time series model with two
      related objectives: the reconstruction of immunity patterns from data on cases
      and population sizes and the identification of the respective roles of extrinsic
      and intrinsic factors in the dynamics. Extrinsic factors here include both
      seasonality and long-term changes or interannual variability in forcing. Results
      with simulated data show that this semiparametric method successfully recovers
      the decay of immunity and identifies the origin of interannual variability. An
      application to historical cholera data indicates that temporary immunity can be
      long-lasting and decays in approximately 9 yr. Extrinsic forcing of
      transmissibility is identified to have a strong seasonal component along with a
      long-term decrease. Furthermore, noise appears to sustain the multiple
      frequencies in the long-term dynamics. Similar semiparametric models should apply
      to population data other than for disease.

PMID- 15266388
TI  - What is speciation and how should we study it?
AB  - To understand speciation, we first need to know what species are. Yet debates
      over species concepts have seemed endless, with little obvious relevance to the
      study of speciation. Recently, there has been progress in resolving these
      debates, favoring a lineage-based, evolutionary species concept. This progress
      calls for reconsideration of the study of speciation. Traditional speciation
      research based on the biological species concept has led to great advances in
      understanding how nonallopatric speciation occurs and how species diverge and
      remain separate from each other. However, this research has neglected the
      question of how new species arise in the first place for the most common
      geographic mode (allopatric). A new and very different research program is needed
      to understand the ecological and evolutionary processes that split an ancestral
      species into new allopatric lineages. This research program will connect
      speciation to many other fundamental questions in evolutionary biology, ecology,
      biogeography, and conservation biology.

PMID- 15266389
TI  - What minimal models cannot tell: a comment on "A model of phytoplankton blooms".
AB  - Huppert et al. analyzed a simple model describing bottom-up control of
      phytoplankton blooms. While we appreciate the mathematical aspects of this
      article, we feel that the fit of their model to data of Lake Kinneret is overly
      optimistic because the time axis was rescaled in an arbitrary way. Furthermore,
      one of the main conclusions of the article (bottom-up control is more likely to
      occur than top-down control) cannot, in our opinion, be drawn from a minimal
      model because such a model focuses on one explanation. It cannot be used to
      reveal the relative importance of alternative explanations.

PMID- 15266391
TI  - Dynamics of production of sexual forms in aphids: theoretical and experimental
      evidence for adaptive "coin-flipping" plasticity.
AB  - The best strategy for an organism to deal with unpredictable environmental
      conditions is a stochastic one, but it is not easy to distinguish it from
      nonadaptive randomness in phenotype production, and its convincing demonstrations
      are lacking. Here we describe a new method for detection of adaptive stochastic
      polyphenism and apply it to the following problem. In fall, each female of the
      bird cherry-oat aphid, Rhopalosiphum padi, faces a decision either to produce
      sexuals, which mate and lay cold-tolerant eggs, or to continue production of cold
      sensitive parthenogenetic females, which potentially yields a higher population
      growth rate but is risky because a cold winter can kill all of her descendants.
      Using a simulation model, we show that global investment in sexual reproduction
      should be proportional to winter severity and that variance in the peak date of
      production of sexual individuals should depend on climate predictability. Both
      predictions are validated against standardized trap data on aphid flight
      accompanied by meteorological data, and the predictions support adaptive
      phenotypic plasticity.

PMID- 15266392
TI  - Evolution of cross-feeding in microbial populations.
AB  - Although limited by a single resource, microbial populations that grow for long
      periods in continuous culture (chemostat) frequently evolve stable polymorphisms.
      These polymorphisms may be maintained by cross-feeding, where one strain
      partially degrades the primary energy resource and excretes an intermediate that
      is used as an energy resource by a second strain. It is unclear what selective
      advantage cross-feeding strains have over a single competitor that completely
      degrades the primary resource. Here we show that cross-feeding may evolve in
      microbial populations as a consequence of the following optimization principles:
      the rate of ATP production is maximized, the concentration of enzymes of the
      pathway is minimized, and the concentration of intermediates of the pathway is
      minimized.

PMID- 15266394
TI  - Evolution by polyploidy and gene regulation in Anura.
AB  - The evolution of the metazoa has been characterized by gene redundancy, generated
      by polyploidy, tandem duplication and retrotransposition. Polyploidy can be
      detected by looking for duplicated chromosomes or segments of orthologous
      chromosomes in post-polyploid animals. It has been proposed that the evolutionary
      role of polyploidy is to provide extra-copies of genes, whose subsequent
      alteration leads to new functions, increased biological complexity, and,
      ultimately, speciation. We review the theory of evolution by genome duplication,
      basing our arguments on findings from autopolyploid anurans and fish, undergoing
      post-polyploidy diploidization. We conclude that: 1) the high genetic variability
      of autotetraploid anurans is a result of tetrasomic expression, based on studies
      of isozymes and other proteins. 2) Epigenetic mechanisms mediate the reduced
      expression or silencing of redundant copies of genes in the regulation of gene
      expression of these tetraploids. This conclusion is based on data concerning
      ribosomal and hemoglobin gene activity. 3) Duplication of the genome may have
      occurred more than once in the phylogeny of the anurans, as exemplified by 4n and
      8n Leptodactylidae species.

PMID- 15266393
TI  - Efficient computation of significance levels for multiple associations in large
      studies of correlated data, including genomewide association studies.
AB  - Large exploratory studies, including candidate-gene-association testing,
      genomewide linkage-disequilibrium scans, and array-expression experiments, are
      becoming increasingly common. A serious problem for such studies is that
      statistical power is compromised by the need to control the false-positive rate
      for a large family of tests. Because multiple true associations are anticipated,
      methods have been proposed that combine evidence from the most significant tests,
      as a more powerful alternative to individually adjusted tests. The practical
      application of these methods is currently limited by a reliance on permutation
      testing to account for the correlated nature of single-nucleotide polymorphism
      (SNP)-association data. On a genomewide scale, this is both very time-consuming
      and impractical for repeated explorations with standard marker panels. Here, we
      alleviate these problems by fitting analytic distributions to the empirical
      distribution of combined evidence. We fit extreme-value distributions for fixed
      lengths of combined evidence and a beta distribution for the most significant
      length. An initial phase of permutation sampling is required to fit these
      distributions, but it can be completed more quickly than a simple permutation
      test and need be done only once for each panel of tests, after which the fitted
      parameters give a reusable calibration of the panel. Our approach is also a more
      efficient alternative to a standard permutation test. We demonstrate the accuracy
      of our approach and compare its efficiency with that of permutation tests on
      genomewide SNP data released by the International HapMap Consortium. The
      estimation of analytic distributions for combined evidence will allow these
      powerful methods to be applied more widely in large exploratory studies.

PMID- 15266395
TI  - Diagnosis of human visceral leishmaniasis by PCR using blood samples spotted on
      filter paper.
AB  - The polymerase chain reaction (PCR) is a simple, rapid procedure that has been
      adapted for the diagnosis of leishmaniasis. In the present study, 85 blood
      samples and seven bone marrow aspirates from 85 patients with clinical symptoms
      suggestive of visceral leishmaniasis from the metropolitan region of Belo
      Horizonte in the Brazilian State of Minas Gerais were screened using molecular
      and serological techniques. Samples that were negative (N = 12) and positive (N =
      19) in parasitological and serological tests were used as controls. Of the 85
      samples analyzed by PCR, 61 (71.7%) showed the expected amplification products in
      agarose gels. However, when the technique was combined with molecular
      hybridization, 72 samples (83.5%) gave a positive signal on film. Nineteen
      patients with Leishmania parasites in bone marrow cultures (positive controls)
      showed PCR hybridization in whole-blood samples, as did the seven bone marrow
      aspirates positive for Leishmania. None of the negative controls reacted in PCR
      or in an indirect immunofluorescent assay. These results indicate that PCR could
      replace the conventional parasitological examination in the diagnosis of
      leishmaniasis since it provides very satisfactory results with blood samples
      spotted on filter paper.

PMID- 15266396
TI  - A low prevalence of cystic fibrosis in Uruguayans of mainly European descent.
AB  - Cystic fibrosis is the most common hereditary disease in populations of European
      descent, with its prevalence depending on the populations and ethnic groups
      studied. In contrast to Europe and North America, there is little information
      about this disease in Latin America. Uruguay currently has a human population of
      3,000,000, with a low rate of miscegenation and no remaining isolated Amerindian
      groups. In the present study, we estimated the prevalence of cystic fibrosis in
      this country based on the detection of DeltaF508 mutation carriers in 500
      unrelated individuals and on the frequency of individuals homozygous for this
      mutation within the affected population. The latter was calculated from the
      frequency of the different mutations and genotypes observed in a sample of 52
      previously described patients with confirmed cystic fibrosis. A theoretical
      estimate of the prevalence of cystic fibrosis based on anthropological data
      suggested a frequency of 25 affected individuals/100,000 inhabitants. However,
      our data indicated that the true prevalence in the population was considerably
      lower (6.9 cases/100,000 inhabitants).

PMID- 15266397
TI  - Standardization of conditions for the metabolic activation of N
      nitrosodiethylamine in mutagenicity tests.
AB  - Like all nitrosamines, N-nitrosodiethylamine (NDEA) requires metabolic activation
      in order to exert its carcinogenic effects. This activation involves cytochrome
      P450s (CYP), which generates unstable metabolites that react with the DNA of
      cells in the immediate vicinity of metabolite formation. Although NDEA is
      carcinogenic, it has been considered a weak mutagen in classic genotoxicity
      assays. We used optimized Salmonella/mammalian microsome genotoxicity assays to
      assess the mutagenicity and toxicity of low concentrations of NDEA. Using a fixed
      concentration of NDEA (36.5 mg/ml), we varied the length of preincubation in the
      presence of different concentrations of an S9 metabolic activation mixture.
      Salmonella typhimurium strains TA97 and TA102 were resistant to NDEA-induced
      mutagenesis, even after a preincubation of up to 120 min and the use of different
      concentrations of the S9 mix. Strain TA98 was susceptible to mutagenesis by NDEA
      in the absence of the S9 mix and after preincubation with NDEA for 90 min. When
      bacteria of this strain were preincubated with NDEA for 60 min, mutagenesis was
      detected at an S9 mix concentration >9.55 mg/ml. NDEA also induced mutagenesis in
      strain TA100 after preincubation for 90 or 120 min, and this effect was dependent
      on the S9 concentration. E. coli strain BH990 also showed a concentration
      dependent response, with only 60% of the cells surviving after a 120-min
      preincubation with NDEA in the presence of 19.1 mg S9 mix/ml.

PMID- 15266398
TI  - Genetic organization and expression of citrate permease in lactic acid bacteria.
AB  - Citrate is present in many natural substrates, such as milk, vegetables and
      fruits, and its metabolism by lactic acid bacteria (LAB) plays an important role
      in food fermentation. The industrial importance of LAB stems mainly from their
      ability to convert carbohydrates into lactic acid and, in some species, like
      Lactococcus lactis and Leuconostoc mesenteroides, to produce C4 flavor compounds
      (diacetyl, acetoin) through citrate metabolism. Three types of genetic
      organization and gene locations, involving citrate metabolism, have been found in
      LAB. Citrate uptake is mediated by a citrate permease, which leads to a membrane
      potential upon electrogenic exchange of divalent citrate and monovalent lactate.
      The internal citrate is cleaved into acetate and oxaloacetate by a citrate lyase,
      and oxaloacetate is decarboxylated into pyruvate by an oxaloacetate
      decarboxylase, yielding a pH gradient through the consumption of scalar protons.

PMID- 15266400
TI  - Patau syndrome with a long survival. A case report.
AB  - Trisomy 13 is a clinically severe entity; 85% of the patients do not survive
      beyond one year, and most children die before completing six months of age. We
      report a female child, 28 months old, white, the fourth child of a non
      consanguineous couple, who presented trisomy 13. The child was born at term, from
      a vaginal delivery, weighing 2600 g. At birth, she was cyanotic, icteric,
      spastic, and cried weakly. The initial clinical examination detected polydactyly
      in the left hand, congenital clubfoot and convex soles, ocular hypertelorism, a
      low nasal bridge, numerous hemangiomas distributed throughout the body,
      cardiomegaly, and perimembranous inter-ventricular communication. There was no
      cleft lip or palate. On physical examination at 18 months old, the child weighed
      6,900 g, had a cephalic perimeter of 41 cm, a thoracic perimeter of 43 cm and was
      76 cm tall. At 28 months, she weighed 10,760 g and was 88.5 cm tall.
      Neuropsychomotor development retardation was evident from birth and, according to
      the psychologist and the social assistant of APAE (Handicapped Parents and
      Friends Association) in Cangucu, Rio Grande do Sul, there was a noticeable
      improvement after physiotherapy and recreational sessions.

PMID- 15266399
TI  - Knockdown of chimeric glucocerebrosidase by green fluorescent protein-directed
      small interfering RNA.
AB  - Gaucher disease, the most common type of lysosomal storage disorder, is
      characterized by an inherited deficiency of the membrane-associated hydrolase,
      glucocerebrosidase. Glucocerebrosidase catalyzes the hydrolysis of
      glucocerebroside to ceramide and glucose, a crucial step in the recycling of
      membrane sphingolipids. The exorbitant cost of the current treatment standard for
      Gaucher disease, enzyme replacement therapy, prevents many from receiving
      treatment. This limitation has led to a wide-spread search for more efficient and
      cost-effective methods of protein production and alternate therapies, resulting
      in a closer examination of glucocerebrosidase biosynthesis and current treatment
      techniques. The use of specific small interfering RNAs (siRNAs) to knock down
      target genes is an attractive option for studying such processes, though a
      glucocerebrosidase-specific siRNA has yet to be reported. We note, however, that
      green fluorescent protein (GFP)-directed siRNAs can not only provide a positive
      control to test siRNA delivery and system integrity, but also serve as a means to
      knock down a fusion partner without having to design siRNAs specific to the
      partner. After effectively co-transfecting COS-1 cells with enhanced GFP (EGFP)
      tagged glucocerebrosidase constructs and GFP-directed siRNAs, we report
      successful knockdown of all EGFP-containing constructs at both the RNA and
      protein levels. This provides a method of examining enzyme biosynthesis and
      treatment options. Furthermore, this technique is applicable to other systems,
      since we have demonstrated the usefulness of GFP as a siRNA target in mammalian
      cells when fused to another gene of interest.

PMID- 15266401
TI  - Comparative cytogenetic studies of Curimatidae (Pisces, Characiformes) from the
      middle Parana River (Argentina).
AB  - Almost all species of the Curimatidae family have a stable karyotype, with a
      diploid number of 54 metacentric (M) and submetacentric (SM) chromosomes, and one
      sole nucleolus organizer pair. This family has considerable specific diversity in
      Argentinean fluvial basins; however, no cytogenetic data are available. Eight
      species from the Parana River (Argentina): Cyphocharax voga, C. spilotus, C.
      platanus, Steindachnerina brevipinna, S. conspersa, Curimatella dorsalis,
      Psectrogaster curviventris, and Potamorhina squamoralevis were analyzed
      cytogenetically. Chromosome preparations were obtained from direct samples and
      through cell culture, and they were processed for conventional, C- and nucleolar
      organizer region-banding. Six of the species exhibited the standard family
      karyotype, with 2n = 54 M-SM and fundamental number of chromosomes (FN) = 108, as
      well as variations in the chromosome formula, and in heterochromatic and
      nucleolar organizer regions. Though nucleolar organizer regions were located on
      only one chromosome pair, they varied in both carrier chromosomes and pairs
      involved. On the other hand, C. platanus showed a complement of 2n = 58 M-SM and
      subtelocentric with FN = 116, and P. squamoralevis presented 2n = 102, with some
      M-SM and a large number of acrocentric chromosomes. Even though the karyotype
      macrostructure appears to be conserved, the speciation process within the family
      has been accompanied by micro-structural rearrangements, as evidenced by pattern
      diversity in the heterochromatin and nucleolar organizer regions. Some changes in
      chromosome macrostructure have also occurred in this group, primarily in C.
      platanus and P. squamoralevis, in which there have been centric dissociations and
      inversions.

PMID- 15266402
TI  - The art and science of writing manuscripts.

PMID- 15266403
TI  - Surviving childhood cancer; now what? Controversies regarding long-term follow
      up.

PMID- 15266404
TI  - Challenges to the measurement of health-related quality of life in children
      receiving cancer therapy.
AB  - Measures of health-related quality of life (HRQL) assess those areas of a
      patient's functioning that are affected by their cancer and its therapy. Although
      HRQL measures are integrated frequently into studies of survivors of childhood
      cancer, their use in the assessment of children receiving therapy has been
      limited by several methodological challenges. These arise from issues specific to
      measuring HRQL in young children, who comprise a large proportion of the
      pediatric oncology population, and from issues associated with assessing HRQL
      during therapy, when the patient's health status is in constant flux. This study
      summarizes the commonly used HRQL measures, and examines factors that impact
      their broad application. These include the influence of developmental changes on
      the content and format of HRQL measures, the role of proxy assessors, the
      important characteristics of measurement tools used to assess patients receiving
      active therapy, and the issues related to the ideal timing of serial HRQL
      assessments in prospective trials.

PMID- 15266405
TI  - Is routine chest radiography necessary for the initial evaluation of fever in
      neutropenic children with cancer?
AB  - BACKGROUND: The yield of routine chest radiography (CXR) as part of the initial
      management of febrile neutropenic pediatric oncology patients is questionable.
      PROCEDURE: We retrospectively analyzed the clinical records of neutropenic
      (absolute neutrophil count < or = 0.5 x 10(9)/L) children with cancer, admitted
      with oral temperature > or = 38 degrees C to our institution, between January
      2001 and October 2002. Following admission, patients received tobramycin plus
      (piperacillin or ticarcillin-clavulanic acid). Admission routine CXRs were
      reviewed. Clinical and radiological features were compared with the discharge
      diagnosis. Age, underlying disease, and the presence of pulmonary symptoms or
      signs were studied as possible predictors of CXR findings related to pneumonia.
      RESULTS: In total, 88 patients experienced 170 episodes of fever. A routine
      admission CXR was obtained for 157 of the episodes. Radiologists found 20 (12.7%)
      abnormal CXR (6 with a segmental or lobar consolidation considered as a
      pneumonia). In addition, two patients with abnormal admission CXR developed lobar
      consolidation on a repeat film, later in their hospital course. There were no
      differences in age and type of underlying disease between children with or
      without pneumonia. Respiratory symptoms were initially present in 58 cases. Seven
      (12%) had pneumonia. Among the 99 asymptomatic cases only one (1%) patient had a
      pneumonia (P = 0.0041). This child had a positive blood culture for P. aeruginosa
      at the time of admission. None of the children had initial therapy modified on
      the basis of radiologic findings. CONCLUSION: In this study, pneumonia is an
      unusual cause of fever (5%), especially in the absence of respiratory signs or
      symptoms (1%). Admission CXR should be reserved for the neutropenic pediatric
      oncology patient presenting with fever and abnormal respiratory findings.

PMID- 15266406
TI  - Efficacy of combined surgery and irradiation for localized Ewings sarcoma family
      of tumors.
AB  - BACKGROUND: Local tumor control for patients with Ewings sarcoma family of tumors
      (ESFT) is favorable when the primary tumor is resectable or small. Local failure
      rates for patients who received combined surgery and RT were reviewed to
      determine outcome and prognostic factors. PROCEDURES: We performed a
      retrospective review of all patients with localized ESFT treated with combined
      definitive surgery and RT between 1978 and 2001, at St. Jude Children's Research
      Hospital. Rates of local failure, survival, and prognostic factors for recurrence
      were determined in 39 patients who received combined local therapy. Systemic
      treatment included vincristine, actinomycin D, cyclophosphamide, and doxorubicin
      (6 patients), with the addition of ifosfamide and etoposide (33 patients).
      RESULTS: With a median follow-up of 8.7 years the 5- and 8-year survival
      estimates were 89.2 +/- 5.4% and 82.8 +/- 7.3%. The 8-year incidence of local
      failure was 10.8 +/- 5.2%. The 8-year local failure rate for patients with
      positive surgical margins was 17% and for negative surgical margins 5% (P =
      0.25). Overall survival was improved for patients with negative surgical margins
      (94 vs. 71%, P = 0.052). Tumor size, site, histologic response, and radiation
      dose did not significantly alter the rate of local failure. CONCLUSIONS: Patients
      with ESFT managed with definitive surgery and irradiation have favorable local
      control rates. Even among patients with unfavorable prognostic factors local
      tumor control remained excellent.

PMID- 15266407
TI  - Carboplatin-based chemotherapy for refractory and recurrent Ewing's tumours.
AB  - BACKGROUND: Failure of first line therapy for the Ewing's family of tumours (EFT)
      is associated with a very poor outlook. Studies of second line chemotherapy are
      therefore necessary to identify active agents and drug combinations. Cisplatin
      based therapy is frequently used in these circumstances but there are few studies
      to clearly define activity and toxicity. This report details outcome in a cohort
      of patients with poor risk EFT treated with a carboplatin-based combination.
      PROCEDURE: Between 1990 and 1998, 23 males and 16 females aged between 6 and 48
      years (median 23) with relapsed or refractory EFT were treated with carboplatin
      based chemotherapy. Previous chemotherapy had included ifosfamide and doxorubicin
      in all but two patients. Twenty patients were treated at the time of recurrence,
      and 19 after a poor response to initial chemotherapy. Treatment comprised of
      carboplatin to give an area under the plasma carboplatin concentration versus
      time curve of (AUC) 6 mg/ml, etoposide 120 mg/m2 for 3 days, and cyclophosphamide
      500-750 mg/m2 for 2 days, repeated every 21 days. RESULTS: A total of 105 cycles
      were given, median 2 per patient (range 1-5). Overall response was 26%, with one
      complete response and nine partial responses. Median time to progression was 10
      weeks (range 2-54). Haematological toxicity was severe requiring dose reductions
      in 53% of patients. Six patients proceeded to high dose consolidation treatment
      with bone marrow or peripheral stem cell rescue. CONCLUSIONS: This combination
      results in a substantial response rate in previously treated patients but with
      significant toxicity. Responses are, however, relatively short.

PMID- 15266408
TI  - Wnt/Frizzled signaling in Ewing sarcoma.
AB  - BACKGROUND: The Ewing sarcoma family of tumors (ESFT) is a set of neuroectodermal
      malignancies that typically presents in the second decade and has a poor
      prognosis due to metastatic disease. Wnt signaling has a critical role in the
      normal development of multiple neuroectodermal tissues and also contributes to
      the neoplastic properties of tumor cells of neuroectodermal origin. PROCEDURE: We
      surveyed the expression of Wnts and their receptors in nine ESFT cell lines by RT
      PCR analysis. We also tested biological response of ESFT cell lines to exogenous
      Wnts in beta-catenin stabilization, actin stress fiber formation, and chemotaxis
      assays. RESULTS: We detected Wnt-10b in all the lines, and most also expressed
      Wnt-5a, Wnt-11, and Wnt-13. Several Frizzleds (Fz) and the Wnt co-receptors, low
      density lipoprotein-receptor-like proteins 5 and 6 were also expressed. We
      observed a marked stimulation of the beta-catenin/canonical Wnt pathway in ESFT
      cells treated with Wnt-3a. Wnt-3a induced morphologic changes characterized by
      the formation of long cytoplasmic extensions in ESFT cells. We also observed
      chemotaxis of ESFT cells in response to Wnt-3a. CONCLUSIONS: These results
      provide evidence that components of Wnt/Fz pathway are expressed and an intact
      Wnt/Frizzled signaling pathway exists in ESFT cell lines. Activation of the Wnt
      pathway in ESFT suggests that Wnt modulates cell motility rather than cell
      proliferation. Hence, activation of this pathway may influence metastatic
      potential of ESFT.

PMID- 15266409
TI  - Impact of location on outcome in children with low-grade oligodendroglioma.
AB  - BACKGROUND: Childhood low-grade oligodendroglioma (WHO grade II) are rare. No
      controlled pediatric study has been published, to generate high level evidence
      for the best treatment. Therefore, we retrospectively analyzed data available
      from pediatric patients. PROCEDURE: We pooled data from two prospective German
      multicentre studies (HIT-DOK and HIT-LGG). Eligibility criteria were: (1) primary
      neoplasm, (2) histology of pure oligodendroglioma WHO grade II, (3) intracranial
      location, (4) age <18 years, (5) date of diagnosis: 1990-2002, (6) observation
      time >6 months. The outcome was analyzed by using the SPSS-software. RESULTS:
      Nineteen boys and 13 girls were eligible (median age 10.3 years). The tumor
      locations included: 26 peripheral tumors (23 cerebral hemisphere, 3 cerebellum),
      and 6 central tumors (4 thalamus, 1 frontal mesencephalon, 1 basal ganglia).
      Resections were classified as complete in 18 (14 cerebral hemispheres, 3
      cerebellum, 1 thalamus) and less than complete in 14 patients (3 subtotal
      resections, 8 partial resections, 3 biopsy). The 5-year event-free survival (EFS)
      and overall survival (OS) rates of all patients were 81.3 and 84.4%, respectively
      (median observation time 3.8 years). All of the 26 children with peripheral
      tumors were alive with no tumor progression, but five of six patients with
      central tumors died of disease (median time to death 1.6 years). This survival
      difference was statistically significant for EFS (P < 0.0001) and OS (P <
      0.0001). The difference between completely resected versus incompletely resected
      tumors was far less striking (P > 0.06). CONCLUSIONS: The outcome of children
      with centrally located low-grade oligodendroglioma is particularly poor, while
      tumors of the cerebral hemispheres and cerebellum carry an excellent prognosis,
      even with minor tumor resection.

PMID- 15266410
TI  - Paediatric malignant tumours of the gastrointestinal tract in the West Midlands,
      UK, 1957-2000: a large population based survey.
AB  - BACKGROUND: To investigate the incidence, clinical characteristics and survival
      of malignant tumours of the gastrointestinal tract in children in the West
      Midlands in Britain over a 44-year span time, to identify any change over this
      period and to compare the data with the world literature. PROCEDURE:
      Retrospective population based study. Fifty-seven patients were identified from
      the records of the West Midlands Regional Children's Tumour Registry. Age
      standardised incidence rates were calculated using the world standardised
      population method. Statistical tests used were the Log rank test and survival
      curves were produced using the Kaplan-Meier method. RESULTS: The age-standardised
      incidence of overall gut tumours during the period 1957-2000 was
      1.10/million/year. The age standardised incidence of non-Hodgkin lymphoma (NHL)
      was calculated as 0.9/million/year and for adenocarcinoma 0.14/million/year.
      CONCLUSION: Malignant tumours of the gastrointestinal tract remain rare in
      children. No changing trends in incidence were observed over the 44-year period.
      NHL was the commonest malignancy overall and of the small bowel while equal
      number of adenocarcinoma and NHL were identified in the large bowel. There was no
      significant difference in survival between sexes, site and age groups in both NHL
      and adenocarcinoma. Survival has improved over the last four decades for NHL
      patients but remains poor for the adenocarcinoma patients.

PMID- 15266411
TI  - Pineal gland abnormalities in Langerhans cell histiocytosis.
AB  - BACKGROUND: The most common types of central nervous system (CNS) disease in
      Langerhans cell histiocytosis (LCH) comprise involvement of the hypothalamic
      pituitary region (HPR) and neurodegenerative changes in the cerebellum, basal
      ganglia or pons. In the review process of magnetic resonance images (MRI) from
      129 LCH patients a high frequency of cysts within or large pineal glands was
      noted by chance. PROCEDURE: To prove whether this observation was specific for
      LCH or not, we compared MRI findings of the HPR in LCH patients with a control
      group of 55 non-LCH patients with the same age and sex distribution. RESULTS: In
      LCH patients, the pineal gland was significantly larger and also the number of
      pineal cysts was significantly higher as compared to the control group. No
      difference was found regarding the size or frequency of cystic changes between
      patients who had received chemotherapy prior to the MRI and untreated patients.
      In the LCH patients, we further found a significant correlation of pineal gland
      enlargement with involvement of the HPR, but not with neurodegenerative changes.
      Analysis of melatonin (the principal hormone of the pineal gland) levels in 24 hr
      urine in 14 LCH patients did not reveal a melatonin deficiency or overproduction
      in the LCH group as compared to 6 normal controls. CONCLUSIONS: The pineal gland
      is another site of possible CNS involvement in LCH. LCH CNS patients did not show
      an overt disturbance in melatonin levels. The role of the pineal gland in CNS LCH
      remains to be defined.

PMID- 15266412
TI  - Patterns of distress in parents of children undergoing stem cell transplantation.
AB  - Parents (N = 151) of children undergoing bone marrow or stem cell transplantation
      (BMT) were assessed in a prospective, longitudinal design with repeated measures
      of distress (mood disturbance, perceived stress, caregiver burden). Parents were
      assessed weekly from admission for BMT (week-1) through week +6 post-BMT,
      followed by monthly assessments through month +6. Concurrent measures of child
      distress (somatic distress, mood disturbance) were also obtained by parent and
      child report. Parents demonstrate modest, but significant elevations in distress,
      particularly during the early period from admission through week +3. Elevations
      in parental distress are transient, and appear to be largely resolved by 4-6
      months post-BMT. Parental distress was unrelated to child age, gender, diagnosis,
      or type of transplant, but was significantly related to parental socioeconomic
      status (SES). Parents from lower SES backgrounds reported greater levels of
      distress throughout the BMT process. Moderate correlations were observed between
      measures of parent and child distress, and level of child distress at the time of
      admission for BMT was predictive parental distress trajectories across the acute
      phase of BMT. These findings point to appropriate targets for intervention to
      reduce transplant-related distress.

PMID- 15266413
TI  - Neonatal prostatic rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is one of the commonest soft tissue sarcomas of childhood, but
      neonatal presentation is extremely rare. This limited experience means there are
      no clear treatment guidelines in this age group. The authors report a boy with
      recurrent attacks of hematuria commencing in the neonatal period, which were
      shown to be from a prostatic rhabdomyosarcoma. To the best of our knowledge this
      is the first reported case of neonatal rhabdomyosarcoma in this site.

PMID- 15266414
TI  - Adventure therapy for adolescents with cancer.
AB  - The objective of this study was to describe adolescents' with cancer experience
      in an adventure therapy program from a health related quality of life (HRQL)
      perspective. A qualitative descriptive research method was used. Eleven
      adolescents and five health professionals participated in a guided group
      adventure therapy expedition in a remote area of Canada. The expedition was
      videotaped and data were collected using an unstructured interview format with
      both adolescents and health professionals. Emerging themes were identified using
      a qualitative descriptive exploratory analysis. Four major themes and related sub
      themes were generated. The major themes were: developing connections,
      togetherness, rebuilding self-esteem, and creating memories. Adventure therapy
      was viewed by the adolescents and health care professionals as a positive
      experience with multiple benefits. This preliminary research will contribute to
      an understanding of adolescents' experiences with cancer and provide a basis for
      future studies evaluating the impact of adventure therapy on HRQL.

PMID- 15266415
TI  - Aggressive bladder carcinoma in a child.
AB  - The brief report describes an unusual case of high grade bladder neoplasm with
      divergent differentiation in a 31 month-old child. The presentation included
      hematuria with tissue fragments and the tumor was confined to the bladder. The
      tumor behaved aggressively despite radical cystectomy, chemotherapy with agents
      known to be effective against epithelial and mesenchymal tumors and radiation
      therapy. Although rare, most malignant bladder neoplasms in children are low
      grade and present in early stages. Sarcomatoid differentiation in the setting of
      high-grade urothelial carcinoma portends a poor prognosis.

PMID- 15266416
TI  - Adenocarcinoma of the cervix and vagina in pediatric patients.
AB  - Here we report our combined analysis of vaginal mesonephric adenocarcinoma (MA)
      in a 13 years old treated at our institution and of reported vaginal or cervical
      MA and clear-cell adenocarcinoma in 37 patients 18 years old or younger. Tumors
      in 27 patients arose in the vagina; 8 (21%) had metastases at diagnosis. The
      predominant symptom was vaginal bleeding; 62% of patients were exposed to
      diethylstilbestrol in utero. The 3-year survival estimate was 71% +/- 11%.
      Surgical treatment and metastasis at diagnosis were significant predictors of
      survival. The association between tumor excision and excellent outcome suggests
      that radical hysterectomy or pelvic exenteration is unnecessary. Radiotherapy as
      an adjunct may have contributed to this outcome.

PMID- 15266417
TI  - What chemotherapy should alveolar paratesticular rhabdomyosarcoma receive?

PMID- 15266418
TI  - Treatment of an infant with a vaginal yolk sac tumour and distant metastases with
      chemotherapy only.

PMID- 15266419
TI  - Is unifocal Langerhans-cell histiocytosis of the orbit a "CNS-Risk" lesion?

PMID- 15266421
TI  - Anticoagulants for acute ischaemic stroke.
AB  - BACKGROUND: Most ischaemic strokes are caused by blood clots blocking an artery
      in the brain. Clot prevention with anticoagulant therapy could have a significant
      impact on patient survival, disability and stroke recurrence. OBJECTIVES: The
      objective of this review was to assess the effect of anticoagulant therapy versus
      control in the early treatment of patients with acute ischaemic stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group trials register (last searched 30
      October 2003). For previous updates of this review, we searched the register of
      the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995),
      and contacted relevant drug companies. SELECTION CRITERIA: Randomised trials
      comparing early anticoagulant therapy (started within two weeks of stroke onset)
      with control in patients with acute presumed or confirmed ischaemic stroke. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected trials for
      inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Twenty
      two trials involving 23,547 patients were included. The quality of the trials
      varied considerably. The anticoagulants tested were standard unfractionated
      heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and
      thrombin inhibitors. Based on nine trials (22,570 patients) there was no evidence
      that anticoagulant therapy reduced the odds of death from all causes (odds ratio
      (OR) = 1.05, 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up.
      Similarly, based on six trials (21,966 patients), there was no evidence that
      anticoagulants reduced the odds of being dead or dependent at the end of follow
      up (OR = 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was
      associated with about 9 fewer recurrent ischaemic strokes per 1000 patients
      treated (OR = 0.76; 95% CI 0.65 to 0.88), it was also associated with a similar
      sized 9 per 1000 increase in symptomatic intracranial haemorrhages (OR = 2.52;
      95% CI 1.92 to 3.30). Similarly, anticoagulants avoided about 4 pulmonary emboli
      per 1000 (OR = 0.60, 95% CI 0.44 to 0.81), but this benefit was offset by an
      extra 9 major extracranial haemorrhages per 1000 (OR = 2.99; 95% CI 2.24 to
      3.99). Sensitivity analyses did not identify a particular type of anticoagulant
      regimen or patient characteristic associated with net benefit. REVIEWERS'
      CONCLUSIONS: Immediate anticoagulant therapy in patients with acute ischaemic
      stroke is not associated with net short- or long-term benefit. The data from this
      review do not support the routine use of any type of anticoagulant in acute
      ischaemic stroke. People treated with anticoagulants had less chance of
      developing deep vein thrombosis (DVT) and pulmonary embolism (PE) following their
      stroke, but these sorts of blood clots are not very common, and may be prevented
      in other ways.

PMID- 15266422
TI  - Clonidine for smoking cessation.
AB  - BACKGROUND: Clonidine was originally used to lower blood pressure. It acts on the
      central nervous system and may reduce withdrawal symptoms in various addictive
      behaviours, including tobacco use. OBJECTIVES: The aim of this review is to
      determine clonidine's effectiveness in helping smokers to quit. SEARCH STRATEGY:
      We searched the Cochrane Tobacco Addiction Group trials register for trials of
      clonidine. Date of the most recent search: May 2004. SELECTION CRITERIA: We
      considered randomized trials of clonidine versus placebo with a smoking cessation
      endpoint assessed at least 12 weeks following the end of treatment. DATA
      COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects,
      the dose and duration of clonidine therapy, the outcome measures, method of
      randomization, and completeness of follow up. The main outcome measure was
      abstinence from smoking after at least 12 weeks follow up in patients smoking at
      baseline. We used the most rigorous definition of abstinence for each trial, and
      biochemically validated rates if available. Where appropriate, we performed meta
      analysis using a fixed effect model. MAIN RESULTS: Six trials met the inclusion
      criteria. There were three trials of oral, and three of transdermal clonidine.
      Some form of behavioural counselling was offered to all participants in five of
      the six trials. There was a statistically significant effect of clonidine in one
      of these trials. The pooled odds ratio for success with clonidine versus placebo
      was 1.89 (95% confidence interval 1.30 to 2.74). There was a high incidence of
      dose-dependent side-effects, particularly dry mouth and sedation. REVIEWERS'
      CONCLUSIONS: Based on a small number of trials, in which there are potential
      sources of bias, clonidine is effective in promoting smoking cessation. Prominent
      side-effects limit the usefulness of clonidine for smoking cessation.

PMID- 15266423
TI  - Nicotine replacement therapy for smoking cessation.
AB  - BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine
      from cigarettes. This reduces withdrawal symptoms associated with smoking
      cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims
      of this review were:to determine the effectiveness of the different forms of NRT
      (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in
      achieving abstinence from cigarettes, or a sustained reduction in amount smoked;
      to determine whether the effect is influenced by the clinical setting in which
      the smoker is recruited and treated, the dosage and form of the NRT used, or the
      intensity of additional advice and support offered to the smoker; to determine
      whether combinations of NRT are more effective than one type alone; to determine
      its effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We
      searched the Cochrane Tobacco Addiction Group trials register in March 2004.
      SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or to
      no treatment, or where different doses of NRT were compared. We excluded trials
      which did not report cessation rates, and those with follow up of less than six
      months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type
      of participants, the dose, duration and form of nicotine therapy, the outcome
      measures, method of randomization, and completeness of follow up. The main
      outcome measure was abstinence from smoking after at least six months of follow
      up. We used the most rigorous definition of abstinence for each trial, and
      biochemically validated rates if available. For each study we calculated summary
      odds ratios. Where appropriate, we performed meta-analysis using a Mantel
      Haenszel fixed effect model. MAIN RESULTS: We identified 123 trials; 103
      contributing to the primary comparison between NRT and a placebo or non-NRT
      control group. The odds ratio (OR) for abstinence with NRT compared to control
      was 1.77 (95% confidence intervals (CI): 1.66 to 1.88). The ORs for the different
      forms of NRT were 1.66 (95% CI: 1.52 to 1.81) for gum, 1.81 (95% CI: 1.63 to
      2.02) for patches, 2.35 (95% CI: 1.63 to 3.38) for nasal spray, 2.14 (95% CI:
      1.44 to 3.18) for inhaled nicotine and 2.05 (95% CI: 1.62 to 2.59) for nicotine
      sublingual tablet/lozenge. These odds were largely independent of the duration of
      therapy, the intensity of additional support provided or the setting in which the
      NRT was offered. In highly dependent smokers there was a significant benefit of 4
      mg gum compared with 2 mg gum (OR 2.20, 95% CI: 1.85 to 3.25). There was weak
      evidence that combinations of forms of NRT are more effective. Higher doses of
      nicotine patch may produce small increases in quit rates. Only one study directly
      compared NRT to another pharmacotherapy. In this study quit rates with bupropion
      were higher than with nicotine patch or placebo. REVIEWERS' CONCLUSIONS: All of
      the commercially available forms of NRT (gum, transdermal patch, nasal spray,
      inhaler and sublingual tablets/lozenges) are effective as part of a strategy to
      promote smoking cessation. They increase the odds of quitting approximately 1.5
      to 2 fold regardless of setting. The effectiveness of NRT appears to be largely
      independent of the intensity of additional support provided to the smoker.
      Provision of more intense levels of support, although beneficial in facilitating
      the likelihood of quitting, is not essential to the success of NRT.

PMID- 15266424
TI  - Pentoxifylline, propentofylline and pentifylline for acute ischaemic stroke.
AB  - BACKGROUND: Methylxanthine derivatives are vasodilators. They also inhibit
      platelet aggregation and thromboxane A2 synthesis, decrease the release of free
      radicals and may be neuroprotective. NOTE: This review covers an area where no
      active research is taking place. It will be updated if relevant information
      becomes available, e.g. on completion of an appropriate study. OBJECTIVES: To
      assess the effect of intravenous or oral methylxanthines (pentoxifylline,
      propentofylline, or pentifylline) in patients with acute ischaemic stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group trials register (last searched
      November 2003). For the first version, we also searched EMBASE (1980 to 1999),
      MEDLINE (1966 to 1999), Science Citation Index (1981 to 1999) and the Ottawa
      Stroke Trials Registry. We also contacted the manufacturers of methylxanthines
      and the principal investigators of the identified trials. SELECTION CRITERIA:
      Randomised trials comparing pentoxifylline, propentofylline or pentifylline with
      placebo or control in patients with definite or presumed acute ischaemic stroke.
      Trials were included if treatment was started within one week of stroke onset.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion
      criteria. Trial quality was assessed. MAIN RESULTS: Five trials were included.
      Four trials tested pentoxifylline in 763 people, and one tested propentofylline
      in 30 people. No trials of pentifylline were found. The odds of early death
      (within four weeks) was non-significantly reduced in patients given a
      methylxanthine drug as compared with those given placebo (odds ratio (OR) 0.64,
      95% confidence interval (CI) 0.41 to 1.02). This non-significant trend to less
      deaths was due mainly to one pentoxifylline trial that found a highly significant
      reduction in early deaths. Two trials reported early death or disability and
      found a non-significant reduction (OR 0.49, 95% CI 0.20 to 1.20). There was no
      significant difference in late death (beyond four weeks), as reported in the
      propentofylline trial involving 30 patients, although the confidence interval was
      wide (OR 0.70, 95% CI 0.13 to 3.68). Data for neurological impairment and
      disability were not in a form suitable for analysis. Data on quality of life,
      stroke recurrence, thromboembolism and bleeding were not reported. REVIEWERS'
      CONCLUSIONS: There is not enough evidence to assess adequately the effectiveness
      and safety of methylxanthines after acute ischaemic stroke.

PMID- 15266425
TI  - Prostacyclin and analogues for acute ischaemic stroke.
AB  - BACKGROUND: Prostacyclin is an agent with a number of effects on platelets, blood
      vessels and nerve cells which might improve outcome after acute ischaemic stroke.
      NOTE: This review covers an area where no active research is taking place. It
      will be updated if relevant information becomes available, e.g. on completion of
      an appropriate study. OBJECTIVES: The objective of this review was to assess the
      effect of prostacyclin or analogues on survival in people with acute ischaemic
      stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register
      (last searched November 2003). For the first version, we also searched EMBASE
      (1980 to 1999), MEDLINE (1966 to 1999), Science Citation Index (1981 to 1999) and
      the Ottawa Stroke Trials Registry. We also contacted the manufacturers of
      prostacyclin and the principal investigators of the identified trials. SELECTION
      CRITERIA: Randomised trials comparing prostacyclin or analogues with placebo or
      control. Trials where people were entered within one week of stroke onset were
      included. DATA COLLECTION AND ANALYSIS: Information on the methods of
      randomisation, blinding, analysis, the number of patients randomised, dose and
      timing of prostacyclin or analogue, patient withdrawals, the number of deaths
      occurring in each trial, and trial quality, were collected and assessed. MAIN
      RESULTS: Five trials involving 191 people were included. Six early deaths (within
      four weeks) occurred with prostacyclin, and nine with placebo (odds ratio (OR)
      0.63, 95% confidence interval (CI) 0.22 to 1.85). One trial of 32 patients
      reported late deaths (by 10 to 18 months) in 50% of patients in each group.
      REVIEWERS' CONCLUSIONS: Too few patients have been studied in randomised trials
      to allow conclusions to be drawn about the effect of prostacyclin treatment on
      survival of people with acute stroke.

PMID- 15266426
TI  - Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory
      drugs in rheumatoid arthritis.
AB  - BACKGROUND: The effect of low dose corticosteroids, equivalent to 15 mg
      prednisolone daily or less, in patients with rheumatoid arthritis has been
      questioned. We performed a systematic review of trials which compared
      corticosteroids with placebo or non-steroidal, anti-inflammatory drugs.
      OBJECTIVES: To determine whether short-term (i.e. as recorded within the first
      month of therapy), oral low-dose corticosteroids (corresponding to a maximum of
      15 mg prednisolone daily) is superior to placebo and non-steroidal, anti
      inflammatory drugs in patients with rheumatoid arthritis. SEARCH STRATEGY:
      PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL ), reference
      lists were searched until February 2004. SELECTION CRITERIA: All randomised
      studies comparing an oral corticosteroid (not exceeding an equivalent of 15 mg
      prednisolone daily) with placebo or a non-steroidal, anti-inflammatory drug were
      eligible if they reported clinical outcomes within one month after start of
      therapy. For adverse effects, long-term trials and matched cohort studies were
      also selected. DATA COLLECTION AND ANALYSIS: Decisions on which trials to include
      were made independently by two observers based on the methods sections of the
      trials. Standardised mean difference (random effects model) was used for the
      statistical analyses. MAIN RESULTS: Ten studies, involving 320 patients, were
      included. Prednisolone had a marked effect over placebo on joint tenderness
      (standardised mean difference 1.30, 95% confidence interval 0.78 to 1.83), pain
      (1.75, 0.87 to 2.64) and grip strength (0.41, 0.13 to 0.69). Measured in the
      original units, the differences were 12 tender joints (6 to 18) and 22 mm Hg (5
      to 40) for grip strength. Prednisolone also had a greater effect than non
      steroidal, anti-inflammatory drugs on joint tenderness (0.63, 0.11 to 1.16) and
      pain (1.25, 0.26 to 2.24), whereas the difference in grip strength was not
      significant (0.31, -0.02 to 0.64). Measured in the original units, the
      differences were 9 tender joints (5 to 12) and 12 mm Hg (-6 to 31). The risk of
      adverse effects, also during moderate- and long-term use, seemed acceptable.
      REVIEWERS' CONCLUSIONS: Prednisolone in low doses (not exceeding 15 mg daily) may
      be used intermittently in patients with rheumatoid arthritis, particularly if the
      disease cannot be controlled by other means. Since prednisolone is highly
      effective, short-term placebo controlled trials studying the clinical effect of
      low-dose prednisolone or other oral corticosteroids are no longer necessary.

PMID- 15266427
TI  - Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke.
AB  - BACKGROUND: Theophylline causes potent cerebral vasoconstriction which decreases
      blood flow in the non-ischaemic areas of the brain and increases collateral blood
      flow surrounding the ischaemic region. NOTE: This review covers an area where no
      active research is taking place. It will be updated if relevant information
      becomes available, e.g. on completion of an appropriate study. OBJECTIVES: The
      objective of this review was to assess the effect of theophylline and its
      analogues, aminophylline and caffeine, in people with confirmed or presumed acute
      ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched November 2003). For the first version, we also searched
      EMBASE (1980 to 1999), MEDLINE (1966 to 1999) and Science Citation Index (1981 to
      1999). We also contacted the principal investigators of the identified trials.
      SELECTION CRITERIA: Randomised trials of theophylline or an analogue compound
      compared with placebo or control in people with confirmed or presumed acute
      ischaemic stroke. Trials were included if treatment was started within one week
      of stroke onset. DATA COLLECTION AND ANALYSIS: Three reviewers applied the
      inclusion criteria, assessed trial quality and extracted data for the first
      version. The review was updated by one reviewer. MAIN RESULTS: Two trials
      involving just 119 patients were included; 6 studies were excluded. Trial quality
      was good. Both of the trials tested aminophylline. Analysis was by intention-to
      treat where possible. No significant difference was shown in early case fatality
      (within four weeks) between aminophylline and placebo although the confidence
      intervals were wide (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.49 to
      2.56). There was no significant difference for early death and deterioration (OR
      0.87, 95% CI 0.41 to 1.88). Death or disability was not significantly reduced by
      treatment based on 73 patients in one trial (OR 0.64, 95% CI 0.24 to 1.68). Data
      for late death and disability were not in a form suitable for analysis. No data
      on quality of life were available. REVIEWERS' CONCLUSIONS: There is not enough
      evidence to assess whether theophylline or its analogues, e.g. aminophylline, are
      safe and improve outcome in people with acute ischaemic stroke.

PMID- 15266428
TI  - Antipsychotic medication for challenging behaviour in people with learning
      disability.
AB  - BACKGROUND: The term 'challenging behaviour', in the absence of psychiatric
      disorder, encompasses a wide range of behaviours that may be harmful to people or
      property, may be difficult to manage and may limit access to community
      facilities. Antipsychotic medications have been used to modify such behaviours in
      people with learning disability, but there is little evidence to suggest that the
      benefits outweigh the risks. OBJECTIVES: To determine the effectiveness of
      antipsychotic medication for people with learning disability and challenging
      behaviour without additional mental illness. SEARCH STRATEGY: Biological
      Abstracts, the Cochrane Library, EMBASE, MEDLINE, PsycINFO and BIOSIS were
      searched. Further references were sought from published trials and pharmaceutical
      companies. Trials were reliably identified and data extracted. SELECTION
      CRITERIA: All randomised controlled trials of antipsychotic medication versus
      placebo. DATA COLLECTION AND ANALYSIS: Reviewers independently evaluated and
      analysed data on an intention to treat basis. Data were evaluated at 4, 8 and 12
      weeks as longer follow-up data were not available. Reviewers assumed that those
      subjects lost to follow-up had a bad outcome. MAIN RESULTS: Only nine randomised
      controlled trials could be included in the analyses. These provided no evidence
      of whether antipsychotic medication helps or harms adults with learning
      disability and challenging behaviour. REVIEWERS' CONCLUSIONS: There are limited
      data on this important issue and more research is urgently needed.

PMID- 15266429
TI  - Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and
      irregular bleeding.
AB  - BACKGROUND: The decline in circulating oestrogen around the time of the menopause
      often induces unacceptable symptoms that affect the health and well being of
      women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and
      progestogen combinations) is an effective treatment for these symptoms. In women
      with an intact uterus, unopposed oestrogen may induce endometrial stimulation and
      increase the risk of endometrial hyperplasia and carcinoma. The addition of
      progestogen reduces this risk but may cause unacceptable symptoms, bleeding and
      spotting which can affect adherence to therapy. OBJECTIVES: The objective of this
      review is to assess which hormone replacement therapy regimens provide effective
      protection against the development of endometrial hyperplasia and/or carcinoma
      with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: We searched the
      Cochrane Menstrual Disorders and Subfertility Group trials register (searched
      January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January
      2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003),
      Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January
      2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The
      search strategy was developed by the Cochrane Menstrual Disorder and Subfertility
      Group. Attempts were also made to identify trials from citation lists of review
      articles and drug companies were contacted for unpublished data. In most cases,
      the corresponding author of each included trial was contacted for additional
      information. SELECTION CRITERIA: The inclusion criteria were randomised
      comparisons of unopposed oestrogen therapy, combined continuous oestrogen
      progestogen therapy and sequential oestrogen-progestogen therapy with each other
      and placebo administered over a minimum treatment period of six months. Trials
      had to assess which regimen was the most protective against the development of
      endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular
      bleeding. DATA COLLECTION AND ANALYSIS: Sixty RCTs were identified. Of these 23
      were excluded and seven remain awaiting assessment. The reviewers assessed the
      thirty included studies for quality, extracted the data independently and odds
      ratios for dichotomous outcomes were estimated. Outcomes analysed included
      frequency of endometrial hyperplasia or carcinoma, frequency of irregular
      bleeding and unscheduled biopsies or dilation and curettage, and adherence to
      therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy when
      compared to placebo was associated with a significant increase in rates of
      endometrial hyperplasia with increasing rates at longer duration of treatment and
      follow up. Odds ratios ranged from (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6
      months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months
      treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 27.5) for 36 months of treatment
      with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate
      dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those
      who took placebo). Irregular bleeding and non adherence to treatment were also
      significantly more likely under these unopposed oestrogen regimens that increased
      bleeding with higher dose therapy. Although not statistically significant, there
      was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen
      compared to no incidence of hyperplasia in the placebo group. The addition of
      progestogens, either in continuous combined or sequential regimens, helped to
      reduce the risk of endometrial hyperplasia and improved adherence to therapy. At
      longer duration of treatment, continuous therapy was more effective than
      sequential therapy in reducing the risk of endometrial hyperplasia. There was
      evidence of a higher incidence of hyperplasia under long cycle sequential therapy
      (progestogen given every three months) compared to monthly sequential therapy
      (progestogen given every month). No increase in endometrial cancer was seen in
      any of t in any of the treatment groups during the duration (maximum of six
      years) of these trials. During the first year of therapy irregular bleeding and
      spotting was more likely in continuous combined therapy than sequential therapy.
      However, during the second year of therapy bleeding and spotting was more likely
      under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent
      evidence in this review that unopposed oestrogen therapy, at moderate and high
      doses, is associated with increased rates of endometrial hyperplasia, irregular
      bleeding and consequent non adherence to therapy. The addition of oral
      progestogens administered either sequentially or continuously is associated with
      reduced rates of hyperplasia and improved adherence to therapy. Irregular
      bleeding is less likely under sequential than continuous therapy during the first
      year of therapy but there is a suggestion that continuous therapy over long
      duration is more protective than sequential therapy in the prevention of
      endometrial hyperplasia. Hyperplasia is more likely when progestogen is given
      every three months in a sequential regimen compared to a monthly progestogen
      sequential regimen.

PMID- 15266430
TI  - Dietary salt reduction or exclusion for allergic asthma.
AB  - BACKGROUND: There is a wide geographical variation in asthma prevalence and one
      explanation may be in dietary salt consumption. OBJECTIVES: To assess the effect
      of dietary sodium reduction in patients with asthma. SEARCH STRATEGY: A search
      was conducted using the Cochrane Airways Group asthma register. Bibliographies of
      included randomised controlled trials (RCTs) were searched for additional
      studies. Authors of identified RCTs were contacted for other studies. The most
      recent search was carried out in February 2004. SELECTION CRITERIA: All studies
      were to be RCTs that involved dietary salt reduction or increased salt intake in
      patients with asthma. Studies of other allergic conditions such as hay fever,
      allergic rhinitis and eczema were considered patients with asthma were separately
      identified. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data
      extracted by two reviewers. All data analysis was conducted using the Cochrane
      Collaboration software (RevMan). MAIN RESULTS: Six RCTs were included in this
      review. All studies were small size and of short duration. Data from only four
      studies could be pooled. Low sodium diet was associated with a significantly
      lower urine sodium excretion than normal or high salt diets. There were no
      significant differences in any asthma outcome between low salt and normal or high
      salt diets, however the confidence intervals were wide. FEV(1) with low salt
      compared to normal diet showed a WMD 0.09 L with a 95% confidence interval
      (95%CI) -0.19 L to 0.38 L, and compared to a high salt diet WMD 0.18 L; 95%CI 
      0.11 L to 0.48 L. Daily PEFR was also non-significantly higher with low salt diet
      compared to normal (WMD 19.52 L/min; 95% CI -21.22 to 60.25) and high salt diet
      (WMD 7.57 L/min; 95% CI -37.52 to 52.67). Reliever bronchodilator with the low
      salt diet when compared to both the normal and high salt diets showed WMD -0.07
      puffs/day; 95%CI -0.94 to 0.81 & WMD -0.65 puffs/day; 95%CI -1.75 to 0.45,
      respectively. REVIEWERS' CONCLUSIONS: Based on currently available evidence it is
      not possible to conclude whether dietary salt reduction has any place in the
      treatment or management of asthma. The results of this review do indicate an
      improvement in pulmonary function with low salt diet, however further large
      scales trials are required before any firm conclusions can be reach.

PMID- 15266431
TI  - Surgery or embolisation for varicocele in subfertile men.
AB  - BACKGROUND: A varicocele is a meshwork of distended blood vessels in the scrotum,
      usually left-sided, due to dilatation of the spermatic vein. Although the concept
      that varicocele causes, and varicocelectomy cures, male subfertility has been
      around for almost fifty years, the mechanisms by which varicocele would affect
      fertility have not yet been satisfactorily explained, and neither have the
      mechanisms by which varicocelectomy would restore fertility. Furthermore, it has
      been questioned whether a causal relation exists at all between the distension of
      the pampiniform plexus and impairment of fertility. OBJECTIVES: To evaluate the
      effect of varicocele treatment on pregnancy rate in subfertile couples. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group
      trials register (searched 12 Sept 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (January 1966 to
      May 2004), EMBASE (January 1985 to May 2004) and reference lists of articles. In
      addition, we hand searched 22 specialist journals in the field from their first
      issue until 2004. We also checked cross references, references from review
      articles, and contacted researchers in the field. SELECTION CRITERIA: RCTs were
      included if they were relevant to the clinical question posed, if they reported
      pregnancy rates as an outcome measure, and if they reported data in treated
      (surgical ligation or radiological embolization of the internal spermatic vein)
      and untreated groups. DATA COLLECTION AND ANALYSIS: Nine studies met the
      inclusion criteria for this review. One was an extension of a previously
      published study (Nieschlag 1995/1998), which left eight studies for analysis
      (Nilsson 1979; Breznik 1993; Madgar 1995; Yamamoto 1996; Nieschlag 1995/1998;
      Grasso 2000; Unal 2001; Krause 2002). All eight only included men from couples
      with subfertility problems, one (Madgar 1995) excluded men with sperm counts <5
      mill/mL, one (Krause 2002) men with sperm counts <2 mill/mL and/or progressive
      motility <10%, two trials involving clinical varicoceles included some men with
      normal semen analysis (Nilsson 1979; Breznik 1993). Three studies (Yamamoto 1996;
      Grasso 2000; Unal 2001) specifically addressed only men with subclinical
      varicoceles. Two authors independently screened potentially relevant trials. Any
      differences of opinion were resolved by consensus (none occurred for this
      review). Studies were excluded from meta-analysis if they made comparisons other
      than those specified above. MAIN RESULTS: The combined Peto odds ratio (OR) of
      the eight studies is 1.10 (95%CI 0.73 to 1.68), indicating no benefit of
      varicocele treatment over expectant management in subfertility couples in whom
      varicocele in the man is the only abnormal finding. REVIEWERS' CONCLUSIONS: There
      is no evidence that treatment of varicocele in men from couples with otherwise
      unexplained subfertility improves the couple's chance of conception.

PMID- 15266432
TI  - Zuclopenthixol acetate for acute schizophrenia and similar serious mental
      illnesses.
AB  - BACKGROUND: Medication used for acute aggression in psychiatry must have rapid
      onset of effect, low frequency of administration and low levels of adverse
      effects. Zuclopenthixol acetate is said to have these properties. OBJECTIVES: To
      estimate the clinical effects of zuclopenthixol acetate for the management of
      acute aggression or violence thought to be due to serious mental illnesses, in
      comparison to other drugs used to treat similar conditions. SEARCH STRATEGY: We
      supplemented past searches of Current Controlled Trials (10/2000), the Cochrane
      Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an
      update search of the Cochrane Schizophrenia Group's Register of trials (September
      2003). SELECTION CRITERIA: All randomised clinical trials involving people
      thought to have serious mental illnesses comparing zuclopenthixol acetate with
      other drugs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by
      two reviewers and cross-checked. We calculated fixed effects relative risks (RR)
      and 95% confidence intervals (CI) for dichotomous data. Where possible, the
      number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by
      intention-to-treat. Mean differences were used for continuous variables. MAIN
      RESULTS: We found no data for the primary outcome, tranquilisation. Compared with
      haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1
      RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at
      reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49
      CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1
      RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol
      acetate had fewer injections over seven days compared with those allocated to
      haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found
      no data on more episodes of aggression or harm to self or others. One trial
      (n=148) reported no significant difference in adverse effects for people
      receiving zuclopenthixol acetate compared with those allocated haloperidol at
      one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or
      clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a
      range of movement disorders (<20%). Three studies found no difference in the
      proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24
      hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those
      allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at
      24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for
      leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). REVIEWERS'
      CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the
      management of psychiatric emergencies in preference to 'standard' treatment have
      to be viewed with caution. Most trials present important methodological flaws and
      findings are poorly reported. This review did not find any suggestion that
      zuclopenthixol acetate is more or less effective in controlling aggressive acute
      psychosis, or in preventing adverse effects than intramuscular haloperidol, and
      neither seemed to have a rapid onset of action. Well-conducted pragmatic
      randomised controlled trials are needed.

PMID- 15266433
TI  - Aversive smoking for smoking cessation.
AB  - BACKGROUND: Aversion therapy pairs the pleasurable stimulus of smoking a
      cigarette with some unpleasant stimulus. The objective is to extinguish the urge
      to smoke. OBJECTIVES: This review has two aims: First, to determine the efficacy
      of rapid smoking and other aversive methods in helping smokers to stop smoking;
      Second, to determine whether there is a dose-response effect on smoking cessation
      at different levels of aversive stimulation. SEARCH STRATEGY: We searched the
      Cochrane Tobacco Addiction Group trials register for studies which evaluated any
      technique of aversive smoking. SELECTION CRITERIA: Randomized trials which
      compared aversion treatments with 'inactive' procedures or which compared
      aversion treatments of different intensity for smoking cessation. Trials must
      have reported follow up of least six months from beginning of treatment. DATA
      COLLECTION AND ANALYSIS: We extracted data in duplicate on the study population,
      the type of aversion treatment, the outcome measure, method of randomization and
      completeness of follow up. The outcome measure was abstinence from smoking at
      maximum follow up, using the strictest measure reported by the authors. Subjects
      lost to follow up were regarded as smokers. Where appropriate, we performed meta
      analysis using a fixed effect model. MAIN RESULTS: Twenty-five trials met the
      inclusion criteria. Twelve included rapid smoking and nine used other aversion
      methods. Ten trials included two or more conditions allowing assessment of a dose
      response to aversive stimulation. The odds ratio (OR) for abstinence following
      rapid smoking compared to control was 1.98 (95% confidence intervals (CI): 1.36
      to 2.90). Several factors suggest that this finding should be interpreted
      cautiously. A funnel plot of included studies was asymmetric, due to the relative
      absence of small studies with negative results. Most trials had a number of
      serious methodological problems likely to lead to spurious positive results. The
      only trial using biochemical validation of all self reported cessation gave a non
      significant result. Other aversion methods were not shown to be effective (odds
      ratio 1.15, 95% confidence interval 0.73 to 1.82). There was a borderline dose
      response to the level of aversive stimulation (OR 1.66, 95% CI: 1.00 to 2.78).
      REVIEWERS' CONCLUSIONS: The existing studies provide insufficient evidence to
      determine the efficacy of rapid smoking, or whether there is a dose-response to
      aversive stimulation. Milder versions of aversive smoking seem to lack specific
      efficacy. Rapid smoking is an unproven method with sufficient indications of
      promise to warrant evaluation using modern rigorous methodology.

PMID- 15266434
TI  - Psychotherapy for bulimia nervosa and binging.
AB  - BACKGROUND: Bulimia nervosa and related syndromes such as binge eating disorder
      are common in young Western women. A specific manual-based form of cognitive
      behaviour therapy (CBT) has been developed for the treatment of bulimia nervosa
      (CBT-BN). Other psychotherapies, some from a different theoretical framework, and
      some modifications of CBT are also used. OBJECTIVES: To evaluate the efficacy of
      CBT and CBT-BN and compare them with other psychotherapies in the treatment of
      adults with bulimia nervosa or related syndromes of recurrent binge eating.
      SEARCH STRATEGY: A handsearch of The International Journal of Eating Disorders
      since its first issue; database searches of MEDLINE, EXTRAMED, EMBASE, PsycInfo,
      CURRENT CONTENTS, LILACS, SCISEARCH, CENTRAL and the The Cochrane Collaboration
      Depression, Anxiety & Neurosis Controlled Trials Register; citation list
      searching and personal approaches to authors were used. SELECTION CRITERIA: All
      studies that have tested any form of psychotherapy for adults with non-purging
      bulimia nervosa, binge eating disorder and/or other types of eating disorders of
      a bulimic type (eating disorder, not otherwise specified, or EDNOS), and which
      applied a randomised controlled and standardised outcome methodology. DATA
      COLLECTION AND ANALYSIS: Data were analysed using the Review Manager software
      program. Relative risks were calculated for binary outcome data. Standardized
      mean differences were calculated for continuous variable outcome data. A fixed
      effects model was used to analyse the data. Sensitivity analyses of a number of
      measures of trial quality were conducted. Data were not reported in such a way to
      permit subgroup analyses, but the effects of treatment on depressive symptoms,
      psychosocial and/or interpersonal functioning, general psychiatric symptoms and
      weight were examined where possible. Funnel plots were drawn to investigate the
      presence of publication bias. MAIN RESULTS: The review supported the efficacy of
      cognitive-behavioural psychotherapy (CBT) and particularly CBT-BN in the
      treatment of people with bulimia nervosa and also (but less strongly due to the
      small number of trials) related eating disorder syndromes. CBT was also shown to
      be effective in group settings. Other psychotherapies were also efficacious,
      particularly interpersonal psychotherapy in the longer-term. Self-help approaches
      that used highly structured CBT treatment manuals, were promising albeit with
      more modest results generally, and their evaluation in bulimia nervosa merits
      further research. Exposure and Response Prevention did not appear to enhance the
      efficacy of CBT.Psychotherapy alone is unlikely to reduce or change body weight
      in people with bulimia nervosa or similar eating disorders. REVIEWERS'
      CONCLUSIONS: There is a small body of evidence for the efficacy of cognitive
      behaviour therapy in bulimia nervosa and similar syndromes, but the quality of
      trials is very variable and sample sizes are often small. More trials of CBT are
      needed, particularly for binge eating disorder and other EDNOS syndromes. Trials
      evaluating other psychotherapies and less intensive psychotherapies should also
      be conducted.

PMID- 15266435
TI  - Vitamin C supplementation for asthma.
AB  - BACKGROUND: Vitamin C is one of the key antioxidant vitamins which is abundant in
      the extracellular fluid lining the lung and low vitamin C intake has been
      associated with pulmonary dysfunction. OBJECTIVES: To evaluate the evidence for
      the efficacy of vitamin C in the treatment of asthma. SEARCH STRATEGY: The
      Cochrane Airways Review Group asthma register was searched and bibliographies of
      studies identified were also checked for further trials. This review has been
      updated by searches to January 2004. SELECTION CRITERIA: Only randomised
      controlled trials were eligible for inclusion. Studies were considered for
      inclusion if they dealt with the treatment of asthma using vitamin C
      supplementation. Two independent reviewers identified potentially relevant
      studies using pre-defined criteria and selected studies for inclusion. DATA
      COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers.
      Information on patients, methods, interventions, outcomes and results was
      extracted using standard forms. MAIN RESULTS: A total of 71 abstracts and titles
      were identified. Sixteen studies were selected for potential inclusion, eight met
      the inclusion criteria. All included studies were placebo-controlled and
      randomised. Only four provided data in a form that permitted further analysis and
      none could be aggregated in a meta analysis. The individual studies did not show
      a significant effect on any asthma outcome. The 2004 update for this review
      includes a large study in 201 adults on inhaled corticosteroids in which
      important benefit from the addition of vitamin C was excluded by the narrow
      confidence intervals of the lung function results. REVIEWERS' CONCLUSIONS: At
      present, evidence from randomised-controlled trials is insufficient to recommend
      a specific role for vitamin C in the treatment of asthma. Further
      methodologically strong and large-scale randomised controlled trials are
      warranted in order to address the question of the effectiveness of vitamin C in
      children with asthma.

PMID- 15266436
TI  - Tamoxifen for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (primary liver cancer) is the third
      commonest cause of cancer mortality world-wide. Survival is poor for patients
      with advanced disease. Trials of tamoxifen for hepatocellular carcinoma have
      conflicting results. OBJECTIVES: To conduct a systematic review of the literature
      to assess the effect of tamoxifen on overall survival, quality-of-life, tumour
      response, and treatment toxicity in people with advanced hepatocellular
      carcinoma. SEARCH STRATEGY: We identified trials from The Cochrane Hepato-Biliary
      Group Controlled Trials Register (January 2004), The Cochrane Central Register of
      Controlled Trials on The Cochrane Library (Issue 3, 2003), and MEDLINE database
      (1966 to November 2003). We searched bibliographies of review articles and
      identified trials, and hand-searched abstracts from relevant other meetings.
      SELECTION CRITERIA: All randomised clinical trials of treatment with tamoxifen
      compared to a control treatment without tamoxifen in people with hepatocellular
      carcinoma, including trials of tamoxifen versus placebo, tamoxifen versus best
      supportive care, and tamoxifen plus other treatment versus the same other
      treatment alone. DATA COLLECTION AND ANALYSIS: Three independent reviewers
      selected studies for inclusion, rated them for methodologic quality components
      (generation of allocation sequence; allocation concealment; blinding; and follow
      up), and extracted data on the specified outcomes. Hazard ratios were derived for
      overall survival where possible. Meta-analysis was performed using a fixed-effect
      model. MAIN RESULTS: Ten randomised trials randomising 1709 patients were
      included. Tamoxifen versus placebo/no intervention had no significant effect on
      overall survival (hazard ratio 1.05; 95% CI 0.94 to 1.16; P = 0.4). This
      comparison showed no statistical heterogeneity (P = 0.2 and I(2 ) = 25.9%).
      Subgroup analysis showed that tamoxifen tended to increase mortality in trials
      with three adequate/three methodological components (hazard ratio 1.15; 95% CI
      0.99 to 1.34; P = 0.06), showed no significant effect in trials with two
      adequate/three methodological components (hazard ratio 1.00; 95% CI 0.84 to 1.18;
      P = 0.98), and tended to reduce mortality in trials with one or less
      adequate/three methodological components (hazard ratio 0.82; 95% CI 0.60 to 1.12;
      P = 0.2), although this may have been confounded by the use of higher doses of
      tamoxifen in the better quality trials. Tamoxifen was associated with adverse
      effects. One trial measured patient quality of life, but the results were not
      reported in detail. REVIEWERS' CONCLUSIONS: These data do not support the use of
      tamoxifen for patients with hepatocellular carcinoma. Further research on the
      effects of tamoxifen in hepatocellular carcinoma does not seem warranted.

PMID- 15266437
TI  - Topical umbilical cord care at birth.
AB  - BACKGROUND: Umbilical cord infection caused many neonatal deaths before aseptic
      techniques were used. OBJECTIVES: To assess the effects of topical cord care in
      preventing cord infection, illness and death. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group trials register (September 2003) and the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2,
      2003). We also contacted experts in the field. SELECTION CRITERIA: Randomized and
      quasi-randomized trials of topical cord care compared with no topical care, and
      comparisons between different forms of care. DATA COLLECTION AND ANALYSIS: Two
      reviewers assessed trial quality and extracted data. MAIN RESULTS: Twenty-one
      studies (8959 participants) were included, the majority of which were from high
      income countries. No systemic infections or deaths were observed in any of the
      studies reviewed. No difference was demonstrated between cords treated with
      antiseptics compared with dry cord care or placebo. There was a trend to reduced
      colonization with antibiotics compared to topical antiseptics and no treatment.
      Antiseptics prolonged the time to cord separation. Use of antiseptics was
      associated with a reduction in maternal concern about the cord. REVIEWERS'
      CONCLUSIONS: Good trials in low-income settings are warranted. In high-income
      settings, there is limited research which has not shown an advantage of
      antibiotics or antiseptics over simply keeping the cord clean. Quality of
      evidence is low.

PMID- 15266438
TI  - Sucrose for analgesia in newborn infants undergoing painful procedures.
AB  - BACKGROUND: Management of pain for neonates is less than optimal. The
      administration of sucrose with and without non-nutritive sucking (pacifiers) has
      been the most frequently studied non-pharmacological intervention for relief of
      procedural pain in neonates. OBJECTIVES: To determine the efficacy, effect of
      dose, and safety of sucrose for relieving procedural pain as assessed by
      validated individual pain indicators and composite pain scores. SEARCH STRATEGY:
      Standard methods as per the Neonatal Collaborative Review Group. A MEDLINE search
      was carried out for relevant randomized controlled trials (RCTs) published from
      January 1966 - March 2004, EMBASE from 1980-2004 and search of the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1,
      2004). Key words and (MeSH) terms included infant/newborn, pain, analgesia and
      sucrose. Language restrictions were not imposed. Bibliographies, personal files,
      the most recent relevant neonatal and pain journals and recent major pediatric
      pain conference proceedings were searched manually. Unpublished studies, or
      studies reported only as abstracts, were not included. Additional information
      from published studies was obtained. SELECTION CRITERIA: RCTs in which term
      and/or preterm neonates (postnatal age maximum of 28 days after reaching 40 weeks
      corrected gestational age) received sucrose via oral syringe, NG-tube, dropper or
      pacifier for procedural pain from heel lance or venepuncture. In the control
      group, water, pacifier or positioning/containing were used. Studies in which the
      painful stimulus was circumcision were excluded. DATA COLLECTION AND ANALYSIS:
      Trial quality was assessed according to the methods of the Neonatal Collaborative
      Review Group. Quality measures included blinding of randomization, blinding of
      intervention, completeness of follow up and blinding of outcome measurement. Data
      were abstracted and independently checked for accuracy by the three
      investigators. STATISTICAL ANALYSIS: The statistical package (RevMan 4.2) of the
      Cochrane Collaboration was used. For meta-analysis, a weighted mean difference
      (WMD) with 95% confidence intervals (CI) using the fixed effects model was
      reported for continuous outcome measures. MAIN RESULTS: Forty-four studies were
      identified for possible inclusion in this review. Seven studies reported only as
      abstracts, and sixteen additional studies were excluded, leaving 21 studies
      (1,616 infants) included in this review. Sucrose in a wide variety of dosages was
      generally found to decrease physiologic (heart rate) and behavioural (the mean
      percent time crying, total cry duration, duration of first cry, and facial
      action) pain indicators and composite pain scores in neonates undergoing heel
      stick or venepuncture. When pain scores (Premature Infant Pain Profiles) were
      pooled across 3 studies (Gibbins 2001; Johnston 1999a; Stevens 1999), they were
      significantly reduced in infants who were given sucrose (dose range 0.012 g to
      0.12 g) compared to the control group, [WMD -1.64 (95% CI -2.47,- 0.81); p =
      0.0001] at 30 seconds and [WMD -2.05, (95% CI -3.08, -1.02); p = 0.00010] at 60
      seconds after heel lance. When results for change in heart rate were pooled for
      two studies (Haouari 1995, Isik 2000), there were no significant differences
      between changes in heart rate for infants given sucrose (dose range 0.5 g to 0.6
      g) compared to the control group, [WMD 0.90 (95% CI -5.81, 7.61); p = 0.8] at one
      minute and [WMD -6.20 (95% CI -15.27, 2.88); p = 0.18] at three minutes after
      heel lance. REVIEWERS' CONCLUSIONS: Sucrose is safe and effective for reducing
      procedural pain from single painful events (heel lance, venepuncture). There was
      inconsistency in the dose of sucrose that was effective (dose range of 0.012 g to
      0.12 g), and therefore an optimal dose to be used in preterm and/or term infants
      could not be identified. The use of repeated administrations of sucrose in
      neonates needs to be investigated as does the use of sucrose in combination with
      other behavioural (e.g., facilitated tucking, kangaroo care) and pharmacologic
      (e.g., morphine, fentanyl) interventions. Use of sucrose in neonates who are of
      very low birth weight, unstable and/or ventilated also needs to be addressed.

PMID- 15266439
TI  - Surgery for deep venous incompetence.
AB  - BACKGROUND: Chronic deep venous incompetence (DVI) is caused by incompetent vein
      valves and/or the blockage of large calibre leg veins, with a range of symptoms
      including recurrent ulcers, pain and swelling. OBJECTIVES: To establish the
      effectiveness of various surgical procedures for treating DVI. SEARCH STRATEGY:
      Trials were identified through the Cochrane Peripheral Vascular Diseases Group's
      trials register, reference lists of relevant studies, and contact with principal
      investigators of identified trials and world experts in deep venous surgery.
      SELECTION CRITERIA: Randomised controlled trials of surgical treatment for
      patients with DVI. DATA COLLECTION AND ANALYSIS: Reviewers extracted data
      independently. Outcome measures included ambulatory venous pressure (AVP) and
      venous refill time (VRT). MAIN RESULTS: Three trials were included, one trial was
      excluded. Two trials compared external valvuloplasty using limited anterior
      plication (LAP) in combination with ligation (L) of incompetent superficial veins
      (L+LAP) against ligation only (L). The other trial compared external
      valvuloplasty and ligation (V+L) of incompetent superficial veins against
      ligation only (L). Trial participants had primary valvular incompetence with mild
      to moderate symptoms but no venous ulcers.L+LAP produced significant improvement
      in AVP: the mean difference between L+LAP and L groups was -15 mm Hg (95%
      confidence interval (CI) -20.9 to -9.0) at one year and -15 mm Hg (95% CI -21 to 
      8.9) at ten years.AVP values after surgery remained relatively high. Nine of
      eleven valves repaired remained competent after two years of follow up. No
      complications occurred. The overall mean score for clinical outcome was +2
      (moderate improvement) in the L+LAP group compared with +1 (mild improvement) in
      the L group. Patients with deteriorating clinical dynamics over the five years
      preceding surgery had a significantly higher rate of improvement in clinical
      condition in V+L compared to L (81% versus 51%; p < 0.05) after seven years
      follow-up. Patients with stable preoperative clinical dynamics demonstrated a
      similar rate of improvement in both groups (96% versus 90%; p> 0.1). AVPs were
      not performed. REVIEWERS' CONCLUSIONS: These results indicate that ligation and
      valvuloplasty may have produced a moderate and sustained improvement for seven to
      ten years after surgery, in patients with mild to moderate DVI caused by primary
      valvular incompetence. However, there is insufficient evidence to recommend the
      treatment to this subgroup of patients, as the trials were small, used different
      methods of valvuloplasty and different methods of assessment.

PMID- 15266440
TI  - Azoles for allergic bronchopulmonary aspergillosis associated with asthma.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the
      fungus Aspergillus fumigatus that complicates patients with asthma and cystic
      fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis
      remains oral corticosteroids, though this does not completely prevent
      exacerbations and may not prevent the decline in lung function. OBJECTIVES: The
      purpose of this review was to determine the efficacy of azoles in the treatment
      of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the
      Cochrane Airways Group Asthma trials register using the terms: (allergic
      bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary
      aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND
      (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January
      2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole
      antifungal agents compared to placebo or other standard therapy for allergic
      bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were
      not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. Study authors were contacted for additional
      information. Adverse effects information was collected from the trials. MAIN
      RESULTS: Twelve trials were identified, but only three were prospective,
      randomised and controlled. A total of 94 participants were included. One
      demonstrated a reduction in immunological markers of disease activity and symptom
      scores using ketoconazole 400 mg daily for 12 months. There was no significant
      improvement in lung function. The other two examined the use of itraconazole for
      16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to
      19% with placebo (p < 0.01). In the same trial, the number of exacerbations
      requiring oral corticosteroids was 0.4 per patient with itraconazole compared
      with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both
      trials showed that itraconazole treated patients were more likely to have decline
      in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to
      8.15). REVIEWERS' CONCLUSIONS: Itraconazole modifies the immunologic activation
      associated with allergic bronchopulmonary aspergillosis and improves clinical
      outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled
      corticosteroids and itraconazole is a potential concern.

PMID- 15266441
TI  - Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation
      after hip arthroplasty.
AB  - BACKGROUND: Heterotopic bone formation (HBF) in the soft tissues surrounding the
      hip joint is a frequent complication of hip surgery. Non-steroidal anti
      inflammatory drugs (NSAIDs) administered in the immediate perioperative period
      reduce the risk of HBF. However, the magnitude of the effect on HBF, and the
      effects on other associated outcomes, such as pain and physical function, are
      uncertain. OBJECTIVES: To determine the effects of perioperative NSAID therapy
      versus control on the risk of HBF and other outcomes in patients undergoing hip
      arthroplasty. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries
      Group specialised register (October 2002), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library issue 3, 2002), MEDLINE (1966 to October
      2002), EMBASE (1988 to 2002 Week 43), CURRENT CONTENTS (1993 Week 27 to 2002 Week
      44) and reference lists of articles. We also contacted trialists and drug
      manufacturers. SELECTION CRITERIA: All trials which enrolled patients scheduled
      to undergo hip arthroplasty with random or quasi-random allocation to
      perioperative NSAID or control and that recorded post-operative radiographically
      determined HBF. The primary outcome was post-operative radiographic HBF.
      Secondary outcomes were pain, function (including range of motion), gastro
      intestinal and other bleeding complications, and other causes of major morbidity
      or mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      methodological quality and extracted data. All analyses were conducted on
      dichotomised outcomes. MAIN RESULTS: Sixteen randomised and two quasi-randomised
      trials involving a total of 4,763 patients were included. Overall, in 17 trials
      that examined the effects of medium to high doses of NSAIDs, there was a reduced
      risk of developing HBF after hip surgery (59% reduction, 95% confidence interval
      54% to 64% reduction). In contrast, one large trial examining low-dose aspirin,
      demonstrated no effect on the risk of HBF (2% reduction, 95% confidence interval
      15% reduction to 12% increase). There was strong evidence of differences in the
      size of the treatment effects observed between the trials examining medium to
      high doses of NSAIDs, but reasons were not clearly identified. There was a non
      significant one third increased risk of gastro-intestinal side effects among
      patients assigned NSAIDs (29% increase, 95% confidence interval 0% to 76%
      increase). Most of this increase was due to an increased risk of minor gastro
      intestinal complications. Data on the late post-operative outcomes of pain,
      impaired physical function and range of joint movement were few and no formal
      overviews of the effects of NSAIDs on these outcomes were possible. REVIEWERS'
      CONCLUSIONS: Perioperative NSAIDs, apart from low dose aspirin, appear to produce
      between a one half and two thirds reduction in the risk of HBF. With routine use,
      such agents may be able to prevent 15-20 cases of HBF among every 100 total hip
      replacements performed. However, while medium to high doses of perioperative
      NSAIDs clearly produce a substantial reduction in the incidence of radiographic
      HBF, there remains some uncertainty about short-term side effects of treatment
      and substantial uncertainty about effects on long-term clinical outcomes such as
      chronic pain and impaired physical function. The net effect of routine HBF
      prophylaxis with NSAIDs requires formal assessment in a randomised trial designed
      to determine the balance of benefits and risks for all outcomes.

PMID- 15266442
TI  - Amantadine and rimantadine for preventing and treating influenza A in adults.
AB  - BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral
      properties, but these drugs are not widely used due to a lack of knowledge of
      their potential value and concerns about possible adverse effects. OBJECTIVES:
      The objective of this review was to assess the effectiveness and safety
      ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to November week 2, 2003),
      EMBASE (January 1990 to September 2003) and the reference lists of articles. We
      also contacted manufacturers, researchers and authors. SELECTION CRITERIA:
      Randomised and quasi-randomised studies comparing amantadine and/or rimantadine
      with placebo, control antivirals or no intervention, or comparing doses or
      schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND
      ANALYSIS: For prevention trials the numbers of participants with clinical
      influenza (influenza-like-illness or ILI), i.e. confirmed influenza A, and
      adverse effects were analysed. Analysis for treatment trials included the mean
      duration of fever and length of hospital stay, and the number of adverse effects.
      MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI)
      13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced
      duration of fever by one day (95% CI 0.7 to 1.3). Rimantadine demonstrated
      comparable effectiveness, but there were fewer trials and the results for
      prevention were not statistically significant. Both amantadine and rimantadine
      induced significant gastrointestinal adverse effects. Adverse effects of the
      central nervous system and study withdrawals were significantly more common with
      amantadine than rimantadine. REVIEWERS' CONCLUSIONS: Amantadine and rimantadine
      have comparable effectiveness in the prevention and treatment of influenza A in
      healthy adults, although rimantadine causes fewer adverse effects than
      amantadine.

PMID- 15266443
TI  - Antibiotics for preventing recurrent urinary tract infection in non-pregnant
      women.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common health care problem.
      Recurrent UTI (RUTI) in healthy non-pregnant women is defined as three or more
      episodes of UTI during a twelve month period. Long-term antibiotics have been
      proposed as a prevention strategy for RUTI. OBJECTIVES: To determine the efficacy
      (during and after) and safety of prophylactic antibiotics used to prevent
      uncomplicated RUTI in adult non-pregnant women. SEARCH STRATEGY: We searched
      MEDLINE (1966-April 2004), EMBASE (1980-January 2003), Cochrane Central Register
      of Controlled Trials( in The Cochrane Library Issue 1, 2004) and reference lists
      of retrieved articles SELECTION CRITERIA: Any published randomised controlled
      trial where antibiotics were used as prophylactic therapy in RUTI. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Statistical analyses were performed using the random effects
      model and the results expressed as relative risk (RR) with 95% confidence
      intervals (CI). MAIN RESULTS: Nineteen studies involving 1120 women were eligible
      for inclusion. Antibiotic versus antibiotic (10 trials, 430 women): During active
      prophylaxis the rate range of microbiological recurrence patient-year (MRPY) was
      0 to 0.9 person-year in the antibiotic group against 0.8 to 3.6 with placebo. The
      RR of having one microbiological recurrence (MR) was 0.21 (95% CI 0.13 to 0.34),
      favouring antibiotic and the NNT was 1.85. For clinical recurrences (CRPY) the RR
      was 0.15 (95% CI 0.08 to 0.28). The NNT was 1.85. The RR of having one MR after
      prophylaxis was 0.82 (95% CI 0.44 to 1.53). The RR for severe side effects was
      1.58 (95% CI 0.47 to 5.28) and for other side effects the RR was 1.78 (CI 1.06 to
      3.00) favouring placebo. Side effects included vaginal and oral candidiasis and
      gastrointestinal symptoms. Antibiotic versus antibiotic (eight trials, 513
      women): These trials were not pooled. Weekly pefloxacin was more effective than
      monthly. The RR for MR was 0.31(95% CI 0.19 to 0.52). There was no significant
      difference in MR between continuous daily and postcoital ciprofloxacin.
      REVIEWERS' CONCLUSIONS: Continuous antibiotic prophylaxis for 6-12 months reduced
      the rate of UTI during prophylaxis when compared to placebo. After prophylaxis
      two studies showed nodifference between groups. There were more adverse events in
      the antibiotic group. One RCT compared postcoital versus continuous daily
      ciprofloxacin and found no significant difference in rates of UTIs, suggesting
      that postcoital treatment could be offered to woman who have UTI associated with
      sexual intercourse.

PMID- 15266444
TI  - Hip protectors for preventing hip fractures in the elderly.
AB  - BACKGROUND: Hip fracture in the elderly usually results from a fall on the hip.
      Hip protectors have been advocated as a means to reduce the risk of sustaining a
      hip fracture. OBJECTIVES: To determine if external hip protectors reduce the
      incidence of hip fractures in elderly persons following a fall. SEARCH STRATEGY:
      We searched the Cochrane Musculoskeletal Injuries Group trials register (February
      2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 1, 2004), MEDLINE (1966 to February Week 2 2004), EMBASE (1988 to 2004 Week
      08), CINAHL (1982 to February Week 2 2004), other databases and reference lists
      of relevant articles. We also contacted trialists. SELECTION CRITERIA: All
      randomised or quasi-randomised controlled trials comparing the use of hip
      protectors with a control group. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted data. We sought additional
      information from all trialists. MAIN RESULTS: An additional trial with 4169
      participants was included in this update, giving a total of 14 included trials.
      One, which was a study of compliance (adherence) lasting 12 weeks, contributed no
      fracture outcome data. Five studies involving 4316 participants were cluster
      randomised by care unit, nursing home or nursing home ward rather than by the
      individual. Each of these studies reported a reduced incidence of hip fractures
      within those units allocated to receive the protectors. Because the majority of
      these trials had not been analysed to allow for clustering, pooling of their
      results was not undertaken. Pooling of data from five individually randomised
      trials conducted in nursing/residential care settings (1426 participants) showed
      no significant reduction in hip fracture incidence (hip protectors 37/822,
      controls 40/604, relative risk (RR) 0.83, 95% confidence interval (CI) 0.54 to
      1.29). Three individually randomised trials of 5135 community dwelling
      participants, reported no reduction in hip fracture incidence with the hip
      protectors (RR 1.16, 95% CI 0.85 to 1.59). No important adverse effects of the
      hip protectors were reported but compliance, particularly in the long term, was
      poor. REVIEWERS' CONCLUSIONS: There is no evidence of effectiveness of hip
      protectors from studies in which randomisation was by individual patient within
      an institution, or for those living in their own homes. Data from cluster
      randomised studies indicate that, for those living in institutional care with a
      high background incidence of hip fracture, a programme of providing hip
      protectors appears to reduce the incidence of hip fractures. Acceptability by
      users of the protectors remains a problem, due to discomfort and practicality.

PMID- 15266445
TI  - Vaccines for preventing influenza in healthy adults.
AB  - BACKGROUND: Three different types of influenza vaccines are currently produced
      worldwide. None is traditionally targeted to healthy adults. Despite the
      publication of a large number of clinical trials, there is still substantial
      uncertainty about the clinical effectiveness of influenza vaccines and this has
      negative impact on the vaccines acceptance and uptake. OBJECTIVES: To assess the
      effects of vaccines on influenza in healthy adults. To assess the effectiveness
      of vaccines in preventing cases of influenza in healthy adults. To estimate the
      frequency of adverse effects associated with influenza vaccination in healthy
      adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the
      Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January
      1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine
      manufacturers and first or corresponding authors of studies in the review.
      SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing
      influenza vaccines in humans with placebo, control vaccines or no intervention,
      or comparing types, doses or schedules of influenza vaccine. Live, attenuated or
      killed vaccines or fractions thereof administered by any route, irrespective of
      antigenic configuration were considered. Only studies assessing protection from
      exposure to naturally occurring influenza in healthy individuals aged 14 to 60
      (irrespective of influenza immune status) were considered. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and extracted data.
      MAIN RESULTS: Twenty five reports of studies involving 59,566 people were
      included. The recommended live aerosol vaccines reduced the number of cases of
      serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to
      64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy
      of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness
      against clinical influenza cases: 15%(95% CI 8% to 21%) and 25% (95% CI 13% to
      35%) respectively. Overall the percentage of participants experiencing clinical
      influenza decreased by 6%. Use of the vaccine significantly reduced time off work
      but only by 0.16 days for each influenza episode (95% CI 0.04 to 0.29 days);
      Analysis of vaccines matching the circulating strain gave higher estimates of
      efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWERS'
      CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed
      cases of influenza. However, they are not as effective in reducing cases of
      clinical influenza and number of working days lost. Universal immunisation of
      healthy adults is not supported by the results of this review.

PMID- 15266446
TI  - Interventions for emergency contraception.
AB  - BACKGROUND: In emergency contraception a drug or IUD is used to prevent pregnancy
      shortly after unprotected intercourse. Except for some Western-European countries
      and China, emergency contraception is largely under-utilised worldwide. In many
      developing countries lack of access to emergency contraception may subject women
      to unsafe abortions, which contribute significantly to maternal mortality and
      morbidity. Currently, several interventions (IUD, the Yuzpe regimen,
      levonorgestrel, mifepristone, danazol and some combination regimens) are
      available for emergency contraception. Information on the comparative efficacy,
      safety and convenience of these methods is crucial for reproductive health care
      providers and the women they serve. OBJECTIVES: To determine which emergency
      contraceptive method following unprotected intercourse is the most effective,
      safe and convenient to prevent pregnancy. SEARCH STRATEGY: The search included
      the Cochrane Controlled Trials Register, Popline, MEDLINE, Chinese biomedical
      databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction
      (HRP) emergency contraception database (July 2003). Content experts and
      pharmaceutical companies were contacted. SELECTION CRITERIA: Randomised
      controlled trials and controlled clinical trials including women attending
      services for emergency contraception following a single act of unprotected
      intercourse were eligible. DATA COLLECTION AND ANALYSIS: Data on outcomes and
      trial characteristics were extracted in duplicate and independently by two
      reviewers. Quality assessment was also done by two reviewers independently. Meta
      analysis results are expressed as relative risk (RR) using a fixed-effects model
      with 95% confidence interval (CI). In the presence of significant heterogeneity a
      random-effect model was applied. MAIN RESULTS: Forty-eight trials with 33110
      women were included. Most trials were conducted in China (37/48). Levonorgestrel
      is more effective than the Yuzpe regimen in preventing pregnancy (2 trials, RR:
      0.51; 95% CI: 0.31 to 0.83). Single dose (1.5 mg) administration seems to have
      similar effectiveness as the standard 12 hours apart split-dose (0.75 mg twice)
      of levonorgestrel (2 trials, RR: 0.77, 95% CI: 0.45 to 1.30). Levonorgestrel has
      similar effectiveness to mid-dose (8 trials, RR: 1.64; 95% CI: 0.82 to 3.25) or
      low-dose (7 trials, RR: 1.38; 95% CI: 0.93 to 2.05) mifepristone. Low-dose (=< 10
      mg) mifepristone is similarly effective as mid doses (25-50 mg) when only high
      quality trials are considered. Delay in the onset of subsequent menses is the
      main unwanted effect of mifepristone and seems to be dose-related. The Yuzpe
      regimen can be used when levonorgestrel and mifepristone are not available. Half
      dose Yuzpe with single administration is associated with fewer side-effects but
      it is not clear whether it is as effective as the standard Yuzpe regimen (RR:
      1.41; 95% CI: 0.76 to 2.61). REVIEWERS' CONCLUSIONS: Levonorgestrel 1.5 mg (two
      split doses or a single dose) and low and mid-doses (25-50 mg) of mifepristone
      offer high efficacy with an acceptable side-effect profile. Single dose
      simplifies the use of levonorgestrel for emergency contraception without an
      increase in side-effects. However, mifepristone might delay the following
      menstruation, which could increase anxiety, particularly in higher doses. The
      Yuzpe regimen could be used if levonorgestrel or mifepristone are not available.
      The intrauterine device (IUD) is another effective emergency contraceptive, and
      can be kept for ongoing contraception.

PMID- 15266447
TI  - Minilaparotomy and endoscopic techniques for tubal sterilisation.
AB  - BACKGROUND: Worldwide, the most commonly used method of fertility regulation is
      tubal sterilisation. In developed countries sterilisation is generally performed
      by laparoscopy rather than by minilaparotomy, based on the belief that this
      approach is both safe and effective. In developing countries, where the resources
      are limited for the purchase and maintenance of the more sophisticated
      laparoscopic equipment, minilaparotomy may still be the most common approach. In
      both resource poor and industrialised countries using the technique with the
      greatest effectiveness and safety, together with the least costs, is extremely
      important. Though both methods are widely used, the advantages and disadvantages
      of laparoscopic sterilisation compared to mini-laparotomy have not been
      systematically evaluated. The ideal method would be one which is highly
      effective, economical, able to be performed on an outpatient basis, allowing
      rapid resumption of normal activity, producing a minimal or invisible scar and
      having a potential for reversibility. This review considers the methods to enter
      the abdominal cavity through the abdominal wall, either by minilaparotomy,
      laparoscopy or culdoscopy regardless of the technique used for tubal
      sterilisation. OBJECTIVES: To evaluate laparoscopic tubal sterilisation, as
      compared to minilaparotomy in terms of operative morbidity and mortality. Trials
      comparing laparoscopy or minilaparotomy with culdoscopy were also included in the
      review. Different methods used to interrupt tubal patency (excision, occlusion
      and coagulation) and comparison of different forms of anaesthesia will be
      considered in different reviews. SEARCH STRATEGY: Randomised controlled trials
      (RCTs) have been identified by using the search strategy of the Cochrane
      Collaboration. The Cochrane Controlled Trials Register was last searched in 1999
      (Cochrane Library Issue 4, 1999). Reference lists of identified trials have been
      searched. SELECTION CRITERIA: All randomised controlled trials comparing
      laparoscopy, minilaparotomy and/or culdoscopy for tubal sterilisation. Except in
      one trial [Taner 1994] where 4 women underwent curettage at the same time, all
      women requested tubal sterilisation as an interval procedure. DATA COLLECTION AND
      ANALYSIS: Trials under consideration were evaluated for methodological quality
      and appropriateness for inclusion. Data were extracted independently by the
      reviewers. Results are reported as odds ratio for dichotomous outcomes and
      weighted mean differences for continuous outcomes. MAIN RESULTS: Minilaparotomy
      vs laparoscopy: There was no difference in major morbidity between the 2 groups.
      Minor morbidity was significantly less in the laparoscopy group (Peto OR 1.89;
      95% CI 1.38, 2.59). Duration of operation was about 5 minutes shorter in the
      laparoscopy group (WMD 5.34; 95% CI 4.52, 6.16). Minilaparotomy vs culdoscopy:
      Women undergoing culdoscopy had more major morbidity than women for whom
      minilaparotomy was performed (Peto OR 0.14; 95% CI 0.02, 0.98). Duration of
      operation was about 5 minutes shorter in women undergoing culdoscopy (WMD 4.91;
      95% CI 3.82, 6.01). Laparoscopy vs culdoscopy: In the one trial comparing the two
      interventions there were no significant differences between the groups with
      regard to major morbidity. Significantly more women suffered from minor
      morbidities in the culdoscopy group compared to the laparoscopy group (Peto OR
      0.20; 95% CI 0.05, 0.77). REVIEWERS' CONCLUSIONS: Major morbidity seems to be a
      rare outcome for both, laparoscopy and minilaparotomy. The included studies had
      limited power to demonstrate significant differences especially for the
      relatively rare but potentially serious outcomes. Personal preference of the
      woman and/or of the surgeon can guide the choice of technique. Practical aspects
      (e.g. cost, maintenance, and sterilisation of the instruments) must be taken into
      account before implementing the more sophisticated endoscopic techniques in
      settings with limited resources. Culdoscopy is not recommended as it carries a
      higher complication rate.

PMID- 15266448
TI  - Intrauterine insemination versus fallopian tube sperm perfusion for non tubal
      infertility.
AB  - BACKGROUND: Controlled ovarian hyperstimulation (COH) together with intrauterine
      insemination (IUI) is commonly offered to couples with infertility factors not
      involving the fallopian tubes. Intrauterine insemination gained its popularity
      because it is simple, non-invasive and cost-effective technique. Another simple
      non invasive method was introduced called fallopian tube sperm perfusion (FSP).
      This technique was developed to ensure the presence of higher sperm densities in
      the fallopian tubes at the time of ovulation than standard IUI provides.
      Fallopian tube sperm perfusion is based on pressure injection of 4 ml of sperm
      suspension with attempt of sealing of the cervix to prevent semen reflux. The IUI
      technique on the other hand is based on intrauterine injection of 0.5 ml of sperm
      suspension without flushing the tubes. A number of randomised controlled trials
      have been published comparing the efficacy of FSP with standard IUI. There were
      considerable variations in the results. The aim of this review was to determine
      whether outcomes differ between FSP and IUI in improving the probability of
      conception. OBJECTIVES: To investigate whether outcomes differ between fallopian
      tube sperm perfusion and intrauterine insemination in the treatment of non tubal
      subfertility resulting in pregnancies and live births. SEARCH STRATEGY: We
      searched the Menstrual Disorders & Subfertility Group trials register (24 March
      2003), MEDLINE (January 1966 to July 2003) and EMBASE (January 1988 to July
      2003). Abstracts of the American Society for Reproductive Medicine (1987 to 2003)
      and European Society for Human Reproduction and Embryology (1987 to 2003)
      meetings were searched with the same key- or text words. SELECTION CRITERIA: Only
      randomised controlled studies comparing fallopian tube sperm perfusion with
      intrauterine insemination were included in this review. The method of allocation
      was assessed to determine whether each study was truly randomised or pseudo
      randomised. Only first period data of cross-over trials were included for
      analysis. Couples who have been trying to conceive for at least one year were
      included but only when the female partner had patent tubes. DATA COLLECTION AND
      ANALYSIS: Two independent reviewers (AC and MJ) selected the trials for inclusion
      based on the quality of the studies. MAIN RESULTS: Overall six studies involving
      474 couples were included in the meta-analysis. Only one study assessed live
      birth rates (OR 1.17, 95% CI 0.39 3.53). The results for pregnancy rate per
      couple were statistically significant with FSP showing higher pregnancy rates (OR
      1.85, 95% CI 1.23 to 2.79 using the odds ratio with the fixed effect model. To
      check the results the random effect model was used, which gave a wider confidence
      interval which crossed the line of no significance (OR 1.76, 95% CI 0.77 to
      4.05). As a result, these outcomes should be interpreted with caution. Subgroup
      analysis revealed that couples suffering from unexplained subfertility benefit
      from FSP over IUI, resulting in significantly higher pregnancy rates (OR 2.88,
      95% CI 1.73 to 4.78). Excluding studies which used the Foley catheter for tubal
      perfusion resulted in a significant difference favouring FSP for all indications
      (OR 2.42, 95% CI 1.54 to 3.80). REVIEWERS' CONCLUSIONS: FSP may be more effective
      for non-tubal subfertility, but the significant heterogeneity should be taken
      into account. As a result no advice based on the meta-analysis could be given for
      the treatment of non-tubal subfertility. Subgroup analysis, which did not show
      evidence of statistical heterogeneity, suggested that couples with unexplained
      infertility may benefit from FSP over IUI in terms of higher pregnancy rates. FSP
      may therefore be advised in couples with unexplained subfertility. Results
      suggested the possibility of differential effectiveness of FSP depending on
      catheter choice.

PMID- 15266449
TI  - Interventions for primary vesicoureteric reflux.
AB  - BACKGROUND: Vesicoureteric reflux (VUR) results in urine passing, in a retrograde
      manner, up the ureter. Urinary tract infections (UTIs) have been considered to be
      the main cause of permanent renal parenchymal damage in children with reflux.
      Therefore management of these children has been directed at preventing infection
      by antibiotic prophylaxis and/or surgical correction of reflux. However
      controversy remains as to the optimum strategies for management of children with
      primary VUR. OBJECTIVES: To evaluate the benefits and harms of the different
      treatment options for primary VUR. SEARCH STRATEGY: Published and unpublished
      randomised controlled trials (RCTs) were identified from the Cochrane Central
      Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and
      abstracts from conference proceedings. SELECTION CRITERIA: RCTs were included if
      they compared any treatments of VUR including surgery (open and closed
      techniques), antibiotic prophylaxis of any duration, non-invasive techniques such
      as bladder training and any combination of therapies. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently searched the literature, determined trial
      eligibility, assessed quality, extracted and entered data. For dichotomous
      outcomes, results were expressed as relative risk (RR) and 95% confidence
      intervals (CI). Data were pooled using the random effects model. MAIN RESULTS:
      Ten trials involving 964 evaluable children comparing long-term antibiotics and
      surgical correction of VUR with antibiotics (seven trials), antibiotics with no
      treatment (one trial) and different materials for endoscopic correction of VUR
      (two trials) were identified. Risk of UTI by 1-2 and 5 years was not
      significantly different between surgical and medical groups (by 2 years RR 1.07,
      95% CI 0.55 to 2.09; by 5 years RR 0.99; 95% CI 0.79 to 1.26). Combined treatment
      resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43, 95% CI 0.27 to
      0.70) but no concomitant significant reduction in risk of new or progressive
      renal damage at 5 years (RR 1.05, 95% CI 0.85 to 1.29). In one small study no
      significant differences in risk for UTI or renal damage were found between
      antibiotic prophylaxis and no treatment. REVIEWERS' CONCLUSIONS: It is uncertain
      whether the identification and treatment of children with VUR confers clinically
      important benefit. The additional benefit of surgery over antibiotics alone is
      small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics
      for five years, nine reimplantations would be required to prevent one febrile
      UTI, with no reduction in the number of children developing any UTI or renal
      damage.

PMID- 15266450
TI  - Depot bromperidol decanoate for schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia.
      Long-acting depot injections of drugs such as bromperidol decanoate are
      extensively used as a means of long-term maintenance treatment. OBJECTIVES: To
      assess the effects of depot bromperidol versus placebo, oral antipsychotics and
      other depot antipsychotic preparations for people with schizophrenia in terms of
      clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were
      identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue
      2, 1999), Cochrane Schizophrenia Group's Register (May 1999), EMBASE (1980-1999),
      MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials
      were inspected and Janssen-Cilag was contacted in order to identify more trials.
      An update search was undertaken in October 2003. The Schizophrenia Groups trials
      register is based on regular searches of BIOSIS Inside; CENTRAL; CINAHL; EMBASE;
      MEDLINE and PsycINFO; the hand searching of relevant journals and conference
      proceedings, and searches of several key grey literature sources. A full
      description is given in the Group's module. SELECTION CRITERIA: All randomised
      trials focusing on people with schizophrenia where depot bromperidol, oral
      antipsychotics or other depot preparations were sought. Primary outcomes were
      death, clinically significant change in global function, mental state, relapse,
      hospital admission, adverse effects and acceptability of treatment. DATA
      COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and
      cross-checked. Fixed effects relative risks (RR) and 95% confidence intervals
      (CI) were calculated for dichotomous data. Weighted or standardised means were
      calculated for continuous data. Where possible, the number needed to treat
      statistic (NNT) was calculated. Analysis was by intention-to-treat. MAIN RESULTS:
      Four controlled clinical trials were included (total n=117). We identified a
      single small study of six months duration comparing bromperidol decanoate with
      placebo injection. Similar numbers left the study before completion (n=20, 1 RCT,
      RR 0.4 CI 0.1 to 1.6) and there was no clear differences between bromperidol
      decanoate and placebo for a list of adverse effects (n=20, 1 RCT, RR akathisia
      2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI
      0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot we
      found no important change on global outcome (n=30, RR no clinical important
      improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and
      haloperidol decanoate had less relapses than those given bromperidol decanoate
      (n=77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol
      decanoate required additional antipsychotic medication somewhat more frequently
      than those taking fluphenazine decanoate and haloperidol decanoate but the
      results did not reach conventional levels of statistical significance (n=77, 2
      RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in
      both groups (n=77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol
      decanoate group with the same frequency as those allocated other depots (n=97, 3
      RCTs, RR 1.92 CI 0.8 to 4.6). Anticholinergic adverse effects were equally common
      between bromperidol and other depots (n=47, RR 3.13 CI 0.7 to 14.0) and
      additional anticholinergic medication was needed with equal frequency in both
      depot groups, although results did tend to favour the bromperidol decanoate group
      (n=97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was
      similar in both depot groups (n=77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). REVIEWERS'
      CONCLUSIONS: Currently, minimal poorly reported trial data suggests that
      bromperidol decanoate may be better than placebo injection but less valuable than
      fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it
      may be a viable choice, especially when there are reasons not to use fluphenazine
      or haloperidol decanoate. Well-conducted and reported randomised trials are
      needed to inform practice in Belgium, Germany, Italy and the Netherlands.

PMID- 15266451
TI  - Decongestants and antihistamines for acute otitis media in children.
AB  - BACKGROUND: Acute otitis media (AOM) is a common and important source of
      morbidity in children, although most cases resolve spontaneously. While
      frequently recommended, decongestant and antihistamine therapy is of unclear
      benefit. OBJECTIVES: To determine the efficacy of decongestant and antihistamine
      therapy in children with AOM on outcomes of AOM resolution, symptom resolution,
      medication side effects, and complications of AOM. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 3, 2003); MEDLINE (January 1966 to December 2003), EMBASE (January
      1990 to July 2003) and reference lists of articles for this updated review. We
      also contacted study authors and pharmaceutical companies. SELECTION CRITERIA:
      Randomized controlled trials evaluating decongestant or antihistamine treatment
      for children with AOM were included. Patient-oriented outcomes were considered
      most relevant. There were no quality or language restrictions. DATA COLLECTION
      AND ANALYSIS: Investigators independently evaluated studies for inclusion,
      performed validity assessments, and completed data extraction. Dichotomous data
      were pooled to generate relative risks; homogeneity was assessed using
      approximate chi-square tests. MAIN RESULTS: Fifteen trials involving 2695 people
      were included. Only the combined decongestant-antihistamine group demonstrated
      statistically lower rates of persistent AOM at the two week period (fixed
      relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.96; number needed
      to treat (NNT) 10). No benefit was found for early cure rates, symptom
      resolution, prevention of surgery or other complications. There was a five to
      eight -fold increased risk of side effects for those receiving an intervention,
      which reached statistical significance for all decongestant groupings. Validity
      sub analyses demonstrated that lower quality studies found benefit, while
      analysis of those studies with higher validity scores found no benefit of
      treatment. REVIEWERS' CONCLUSIONS: Given lack of benefit and increased risk of
      side effects, these data do not support the use of decongestant treatment in
      children with AOM. There was a small statistical benefit from combination
      medication use but the clinical significance is minimal and study design may be
      biasing the results. Thus, the routine use of antihistamines for treating AOM in
      children cannot be recommended.

PMID- 15266452
TI  - Support surfaces for pressure ulcer prevention.
AB  - BACKGROUND: Pressure ulcers (also known as bedsores, pressure sores, decubitus
      ulcers) are areas of localised damage to the skin and underlying tissue due to
      pressure, shear or friction. They are common in the elderly and immobile and
      costly in financial and human terms. Pressure-relieving beds, mattresses and seat
      cushions are widely used as aids to prevention in both institutional and non
      institutional settings. OBJECTIVES: This systematic review seeks to answer the
      following questions: to what extent do pressure-relieving cushions, beds,
      mattress overlays and mattress replacements reduce the incidence of pressure
      ulcers compared with standard support surfaces? how effective are different
      pressure-relieving surfaces in preventing pressure ulcers, compared to one
      another? SEARCH STRATEGY: The Specialised Trials Register of the Cochrane Wounds
      Group (compiled from regular searches of many electronic databases including
      MEDLINE, CINAHL and EMBASE plus handsearching of specialist journals and
      conference proceedings) was searched up to January 2004, Issue 3, 2004 of the
      Cochrane Central Register of Controlled Trials was also searched. The reference
      sections of included studies were searched for further trials. SELECTION
      CRITERIA: Randomised controlled trials (RCTs), published or unpublished, which
      assessed the effectiveness of beds, mattresses, mattress overlays, and seating
      cushions for the prevention of pressure ulcers, in any patient group, in any
      setting. RCTs were eligible for inclusion if they reported an objective, clinical
      outcome measure such as incidence and severity of new of pressure ulcers
      developed. Studies which only reported proxy outcome measures such as interface
      pressure were excluded. DATA COLLECTION AND ANALYSIS: Trial data were extracted
      by one researcher and checked by a second. The results from each study are
      presented as relative risk for dichotomous variables. Where deemed appropriate,
      similar studies were pooled in a meta analysis. MAIN RESULTS: 41 RCTs were
      included in the review. Foam alternatives to the standard hospital foam mattress
      can reduce the incidence of pressure ulcers in people at risk. The relative
      merits of alternating and constant low pressure devices, and of the different
      alternating pressure devices for pressure ulcer prevention are unclear.Pressure
      relieving overlays on the operating table have been shown to reduce postoperative
      pressure ulcer incidence, although one study indicated that an overlay resulted
      in adverse skin changes. One trial indicated that Australian standard medical
      sheepskins prevented pressure ulcers. There is insufficient evidence to draw
      conclusions on the value of seat cushions, limb protectors and various constant
      low pressure devices as pressure ulcer prevention strategies.A study of Accident
      & Emergency trolley overlays did not identify a reduction in pressure ulcer
      incidence. There are tentative indications that foot waffle heel elevators, a
      particular low air loss hydrotherapy mattress and an operating theatre overlay
      are harmful. REVIEWERS' CONCLUSIONS: In people at high risk of pressure ulcer
      development, consideration should be given to the use of higher specification
      foam mattresses rather than standard hospital foam mattresses. The relative
      merits of higher-tech constant low pressure and alternating pressure for
      prevention are unclear. Organisations might consider the use of pressure relief
      for high risk patients in the operating theatre, as this is associated with a
      reduction in post-operative incidence of pressure ulcers. Seat cushions and
      overlays designed for use in Accident & Emergency settings have not been
      adequately evaluated.

PMID- 15266453
TI  - Hormonally impregnated intrauterine systems (IUSs) versus other forms of
      reversible contraceptives as effective methods of preventing pregnancy.
AB  - BACKGROUND: In the 1970s a new approach to the delivery of hormonal contraception
      was researched and developed. It was suggested that the addition of a progestogen
      to a non-medicated contraceptive device improved its contraceptive action. An
      advantage of these hormonally impregnated intrauterine systems (IUS) is that they
      are relatively maintenance free, with users having to consciously discontinue
      using them to become pregnant rather than taking a proactive daily decision to
      avoid conception. OBJECTIVES: To assess the contraceptive efficacy, tolerability
      and acceptability of hormonally impregnated intrauterine systems (IUSs) in
      comparison to other reversible contraceptive methods. SEARCH STRATEGY: Literature
      was identified through database searches, reference lists and
      individuals/organisations working in the field. Searches covered the period from
      1972 to November 2003. SELECTION CRITERIA: All randomised controlled trials
      comparing IUSs with other forms of reversible contraceptives and reporting on pre
      determined outcomes in women of reproductive years. The primary outcomes were
      pregnancy due to method/user failure and continuation rate. DATA COLLECTION AND
      ANALYSIS: The quality assessment of studies and data extraction were completed
      independently by two blinded reviewers. A quality checklist was designed to
      identify general methodological and contraceptive specific factors which could
      bias results. Events per women months and single decrement life table rates were
      extracted where possible for pregnancy, continuation, adverse events and reasons
      for discontinuation. Events per total number of women at follow up were collected
      for hormonal side effects and menstrual disturbance. When appropriate, data were
      pooled at the same points of follow up to calculate rate ratios in order to
      determine the relative effectiveness of one method compared to another. For the
      single decrement life table rates, the rate differences were pooled to determine
      the absolute difference in effectiveness of one method compared to another.
      Interventions were only combined if the contraceptive methods were similar. Non
      hormonal IUDs were divided into three categories for the purpose of comparison
      with IUSs: IUDs >250mm2 (i.e. CuT 380A IUD and CuT 380 Ag IUD), IUDs <=250mm2
      (i.e. Nova-T, Multiload, CuT 200 and CuT 220 IUDs) and non-medicated IUDs. MAIN
      RESULTS: Twenty-one RCTs comparing hormonally impregnated IUSs to a reversible
      contraceptive method met the inclusion criteria and it was possible to include
      eight of these in the meta-analyses, four comparing LNG-20 IUSs with non-hormonal
      IUDs, one comparing the LNG-20 IUS with Norplant-2 and three comparing
      Progestasert with non-hormonal IUDs. No significant difference was observed
      between the pregnancy rates for the LNG-20 users and those for the IUD >250mm2
      users. However, women using the LNG-20 IUS were significantly less likely to
      become pregnant than those using the IUD <=250mm2. Women using the LNG-20 IUS
      were more likely to experience amenorrhoea and device expulsion than women using
      IUDs >250mm2. LNG-20 users were significantly more likely than all the IUD users
      to discontinue because of hormonal side effects and menstrual disturbance, which
      on further breakdown of the data was due to amenorrhoea. When the LNG-20 IUS was
      compared to Norplant-2, the LNG-20 users were significantly more likely to
      experience amenorrhoea and oligomenorrhoea, but significantly less likely to
      experience prolonged bleeding and spotting. No other significant differences were
      observed. Progestasert users were significantly less likely to become pregnant
      and less likely to continue on the method than non-medicated IUD users after one
      year, but no significant difference was noted for these two outcomes when
      Progestasert users were compared to IUD<=250mm2 users. The only other significant
      differences found in the meta-analyses were that Progestasert users were less
      likely to expel the device and more likely to discontinue the method because of
      menstrual bleeding and pain than users of IUDs <=250mm2. REVIEWERS' CONCLUSIONl
      the device and more likely to discontinue the method because of menstrual
      bleeding and pain than users of IUDs <=250mm2. REVIEWERS' CONCLUSIONS: Current
      evidence suggests LNG-20 IUS users are no more or less likely to have unwanted
      pregnancies than IUD >250mm2 and Norplant-2 users. The LNG-20 IUS was more
      effective in preventing either intrauterine or extrauterine pregnancies than IUDs
      <=250mm2. The contraceptive effectiveness of Progestasert was significantly
      better than non-medicated IUDs, but no difference was observed when compared to
      IUDs<=250mm2. Continuation of LNG-20 IUS use was similar to continuation of the
      non-hormonal IUDs and Norplant-2. Amenorrhoea was the main reason for the
      discontinuation for the LNG-20 IUS and women should be informed of this prior to
      starting this method.

PMID- 15266454
TI  - Interventions for treating oral leukoplakia.
AB  - BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a small
      but significant proportion of cases changes into cancer. Since most leukoplakias
      are asymptomatic, the primary objective of treatment should be to prevent such
      malignant transformation. OBJECTIVES: To assess effectiveness, safety and
      acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following
      databases were searched for relevant trials: Cochrane Oral Health Group's Trials
      Register, CENTRAL, MEDLINE, EMBASE. Handsearching was performed for the main oral
      medicine journals. References of included studies and reviews were checked. Oral
      medicine experts were contacted through an European mailing list (EURORALMED).
      SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with
      a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical
      and systemic) treatment was included. The primary outcome considered was
      malignant transformation of leukoplakia. Other outcomes considered were clinical
      resolution, histological modification and frequency of adverse effects. DATA
      COLLECTION AND ANALYSIS: Data were collected using a specific extraction form.
      Malignant transformation of leukoplakia, demonstrated by histopathological
      examination, was the main outcome considered. Secondary outcomes included
      clinical resolution of the lesion and variation in dysplasia severity. The
      validity of included studies was assessed by two reviewers, on the basis of the
      method of allocation concealment, blindness of the study and loss of
      participants. Data were analysed by calculating relative risk. When valid and
      relevant data were collected, a meta-analysis of the data was undertaken. MAIN
      RESULTS: The possible effectiveness of surgical interventions, including laser
      therapy and cryotherapy, has never been studied by means of a RCT. Nineteen
      potentially eligible RCTs of non-surgical interventions were identified: eight
      were excluded for different reasons, four were ongoing studies, leaving seven
      studies to be included in the review. Two studies resulted at low risk of bias,
      four at moderate risk of bias and one at high risk of bias. Vitamin A and
      retinoids were tested by five RCTs (245 patients), the other drugs tested were
      bleomycin (one study), mixed tea (one study) and beta carotene (one study).
      Malignant transformation was recorded in just two studies: none of the treatments
      tested showed a benefit when compared with the placebo. Treatment with beta
      carotene and vitamin A or retinoids, was associated with significant rates of
      clinical resolution, compared with placebo or absence of treatment. Whenever
      reported, a high rate of relapse was a common finding. Side effects of variable
      severity were often described; however, interventions were well accepted by
      patients, since drop-out rates were similar between treatment and control groups.
      REVIEWERS' CONCLUSIONS: To date there is no evidence of effective treatment in
      preventing malignant transformation of leukoplakia. Treatments may be effective
      in the resolution of lesion, however relapses and adverse effects are common.

PMID- 15266455
TI  - Pit and fissure sealants for preventing dental decay in the permanent teeth of
      children and adolescents.
AB  - BACKGROUND: Fissure sealants used on occlusal tooth surfaces were introduced in
      the 1960s for protecting pits and fissures from dental caries. Although sealants
      have demonstrated to be effective in preventing caries, their efficacy may be
      related to the background caries prevalence in the population. OBJECTIVES: The
      primary objective of this review was to evaluate the caries prevention of resin
      based pit and fissure sealants and glass ionomer cements or sealants in children
      and adolescents. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's
      Trials Register (last update December 2002), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2002), MEDLINE via
      OVID (1966 to December 2002), EMBASE (1974 to February 2002), SCISEARCH, SIGLE,
      CAplus, INSPEC, JICST-EPLUS, NTIS, PASCAL (February 2002) and DARE, NHS EED, HTA
      (March 2002). Reference lists from included articles and review articles were
      searched for additional relevant articles. All relevant studies in most languages
      were considered and translated. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials of at least 12 months in duration in which sealants
      were used for preventing caries in children and adolescents under 20 years of age
      were included. The primary outcome was the increment in the numbers of carious
      occlusal surfaces of premolars and molars. DATA COLLECTION AND ANALYSIS: In the
      first phase, two reviewers independently examined whether a given study was
      likely to be relevant on the basis of the title, key words and abstract. In the
      second phase, four of the reviewers independently classified studies to be
      included in final analyses. Study authors were contacted for additional
      information. In the split-mouth studies relative risk ratios were calculated for
      the paired differences of tooth surfaces being carious or not. In studies
      comparing resin based sealant with no treatment, fixed effect meta-analyses were
      used to combine the estimates of relative risk ratios. In one parallel group
      study, the mean DFS data as continuous data, the effect estimate being the
      difference in mean DFS, was calculated from data of occlusal surfaces of teeth
      included in the test and control groups. MAIN RESULTS: Eight trials were included
      in this review of which seven trials were split-mouth studies and one a parallel
      group study. Six studies provided data for comparing sealant with no treatment
      and three studies for comparing glass ionomers with resin based sealants. The
      overall effectiveness of resin based sealants in preventing dental decay on first
      molars was high. Based on five split-mouth studies with 5 to 10 year old children
      there were significant differences in favour of the second-generation resin
      sealant compared with no treatment with pooled relative risk values of 0.14,
      0.24, 0.30, 0.43 at 12, 24, 36 and 48 to 54 months respectively. The reductions
      in caries therefore ranged from 86% at 12 months to 57% at 48 to 54 months. The
      24 month parallel group study comparing second-generation resin sealant with
      control in 12 to 13 year old children found also significantly more caries in the
      control group children with DFS = 0.65 (95% CI 0.47 to 0.83). Allocation
      concealment was classified adequate in three of these six studies. However the
      information on background levels of caries in the population was insufficient to
      conduct further analyses to estimate the effectiveness of resin based sealants
      related to baseline caries prevalence. Only one study provided data for the
      comparison between glass ionomer sealant and control. Based on this, there is not
      enough information to say whether ionomer sealants are effective, or not. The
      results of three studies comparing resin sealants with glass ionomer sealants
      were conflicting and the meta-analyses were not carried out. REVIEWERS'
      CONCLUSIONS: Sealing with resin based sealants is a recommended procedure to
      prevent caries of the occlusal surfaces of permanent molars. However, we
      recommend that the caries prevalence level of both individuals and the population
      should be taken into account. In practice, the benefit of sealing should be
      considered locally and specified guidelines for clinicians should be used. The
      methodological quality of published studies concerning pit and fissure sealants
      was poorer than expected.

PMID- 15266456
TI  - Interventions for preventing injuries in problem drinkers.
AB  - BACKGROUND: Alcohol consumption has been linked with injuries through motor
      vehicle crashes, falls, drowning, fires and burns, and violence. In the US, half
      of the estimated 100,000 deaths attributed to alcohol each year are due to
      intentional and unintentional injuries. The identification of effective
      interventions for the reduction of unintentional and intentional injuries due to
      problem drinking is, therefore, an important public health goal. OBJECTIVES: To
      assess the effect of interventions for problem drinking on subsequent injury
      risk. SEARCH STRATEGY: We searched 12 twelve computerized databases: MEDLINE
      (1966-8/96), EMBASE (1982-1/97), Cochrane Controlled Trials Register (1997, issue
      #1), PsycINFO (1967-1/97), CINAHL (1982-10/96), ERIC (1966-12/96), Dissertation
      Abstracts International (1861-11/96), IBSS (1961-1/97), ISTP (1982-1/97) and
      three specialized transportation databases, using terms for problem drinking
      combined with terms for controlled trials; bibliographies of relevant trials; and
      contact with authors and government agencies. The electronic and bibliographic
      searches were updated in May 2002. SELECTION CRITERIA: Randomized controlled
      trials of interventions among participants with problem drinking, which are
      intended to reduce alcohol consumption or to prevent injuries or their
      antecedents, and which measured injury-related outcomes. DATA COLLECTION AND
      ANALYSIS: Two authors extracted data on participants, interventions, follow-up,
      allocation concealment, and outcomes, and independently rated allocation
      concealment quality. MAIN RESULTS: Of 23 eligible trials identified, 22 had been
      completed and 17 provided results for relevant outcomes. Completed trials of
      problem drinkers that compared interventions for problem drinking to no
      intervention reported reduced motor-vehicle crashes and related injuries, falls,
      suicide attempts, domestic violence, assaults and child abuse, alcohol-related
      injuries and injury emergency visits, hospitalizations and deaths. Reductions
      ranged from 27% to 65%. Because few trials were sufficiently large to assess
      effects on injuries, individual effect estimates were generally imprecise. We did
      not combine the results quantitatively because the interventions, patient
      populations, and outcomes were so diverse. The most commonly evaluated
      intervention was brief counseling in the clinical setting. This was studied in
      seven trials, in which injury-related deaths were reduced: relative risk (RR)
      0.65; 95% confidence interval (CI) 0.21 to 2.00. However, this reduction may have
      been due to chance. The majority of trials of brief counseling also showed
      beneficial effects on diverse non-fatal injury outcomes. REVIEWERS' CONCLUSIONS:
      Interventions for problem drinking appear to reduce injuries and their
      antecedents (e.g. falls, motor vehicle crashes, suicide attempts). Because
      injuries account for much of the morbidity and mortality from problem drinking,
      larger studies are warranted to evaluate the effect of treating problem drinking
      on injuries.

PMID- 15266457
TI  - Aciclovir or valaciclovir for Bell's palsy (idiopathic facial paralysis).
AB  - BACKGROUND: The most common disorder of the facial nerve is acute idiopathic
      facial paralysis or Bell's palsy and there may be significant morbidity or
      incomplete recovery associated with severe cases. OBJECTIVES: To assess the
      efficacy of aciclovir or similar agents for treating Bell's palsy. SEARCH
      STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched
      April 2003), MEDLINE (from January 1966 to April 2003), EMBASE (from January 1980
      to April 2003) and LILACS (from January 1982 to April 2003). We also contacted
      authors of identified trials. SELECTION CRITERIA: Randomised or quasi-randomised
      trials of aciclovir or valaciclovir therapy, alone or in combination with any
      other drug, in patients with Bell's palsy. DATA COLLECTION AND ANALYSIS: We
      identified six randomised trials. MAIN RESULTS: Three studies met our inclusion
      criteria, including 246 patients. One study evaluated aciclovir with
      corticosteroid versus corticosteroid alone, another study evaluated aciclovir
      alone versus corticosteroid and a further study evaluated valaciclovir with
      corticosteroid versus corticosteroid alone or versus placebo alone. Incomplete
      recovery after one year: data were not available. An analysis was performed on
      data reported at the end of the study period in each trial. The results from one
      study four months after the start of treatment significantly favoured the
      treatment group, whilst the results of the study three months after the start of
      treatment significantly favoured the control group. The results from the second
      study at four months showed no statistically significant difference between the
      three groups. Adverse events: relevant data were not reported in any of the three
      trials. Complete facial paralysis six months after start of treatment: only one
      patient had complete paralysis upon entering one of the studies. This patient was
      assigned to the control group and the level of recovery attained was not
      reported. Motor synkinesis or crocodile tears one year after start of treatment:
      data were available up to a maximum of four months after onset of paralysis. One
      study reported a significant difference between the treatment groups in favour of
      the aciclovir plus corticosteroid group over corticosteroid alone, another
      demonstrated an inconclusive result with no difference between the aciclovir and
      corticosteroid. The third study did not comment upon these sequelae. REVIEWERS'
      CONCLUSIONS: More data are needed from a large multicentre randomised controlled
      and blinded study with at least 12 months' follow up before a definitive
      recommendation can be made regarding the effect of aciclovir or valaciclovir on
      Bell's palsy.

PMID- 15266458
TI  - Non-invasive physical treatments for chronic/recurrent headache.
AB  - BACKGROUND: Non-invasive physical treatments are often used to treat common types
      of chronic/recurrent headache. OBJECTIVES: To quantify and compare the magnitude
      of short- and long-term effects of non-invasive physical treatments for
      chronic/recurrent headaches. SEARCH STRATEGY: We searched the following databases
      from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science
      Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of
      the Cochrane Pain, Palliative Care and Supportive Care review group. Selected
      complementary medicine reference systems were searched as well. We also performed
      citation tracking and hand searching of potentially relevant journals. SELECTION
      CRITERIA: We included randomized and quasi-randomized controlled trials comparing
      non-invasive physical treatments for chronic/recurrent headaches to any type of
      control. DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted trial
      information and scored trials for methodological quality. Outcomes data were
      standardized into percentage point and effect size scores wherever possible. The
      strength of the evidence of effectiveness was assessed using pre-specified rules.
      MAIN RESULTS: Twenty-two studies with a total of 2628 patients (age 12 to 78
      years) met the inclusion criteria. Five types of headache were studied: migraine,
      tension-type, cervicogenic, a mix of migraine and tension-type, and post
      traumatic headache. Ten studies had methodological quality scores of 50 or more
      (out of a possible 100 points), but many limitations were identified. We were
      unable to pool data because of study heterogeneity. For the prophylactic
      treatment of migraine headache, there is evidence that spinal manipulation may be
      an effective treatment option with a short-term effect similar to that of a
      commonly used, effective drug (amitriptyline). Other possible treatment options
      with weaker evidence of effectiveness are pulsating electromagnetic fields and a
      combination of transcutaneous electrical nerve stimulation [TENS] and electrical
      neurotransmitter modulation. For the prophylactic treatment of chronic tension
      type headache, amitriptyline is more effective than spinal manipulation during
      treatment. However, spinal manipulation is superior in the short term after
      cessation of both treatments. Other possible treatment options with weaker
      evidence of effectiveness are therapeutic touch; cranial electrotherapy; a
      combination of TENS and electrical neurotransmitter modulation; and a regimen of
      auto-massage, TENS, and stretching. For episodic tension-type headache, there is
      evidence that adding spinal manipulation to massage is not effective. For the
      prophylactic treatment of cervicogenic headache, there is evidence that both neck
      exercise (low-intensity endurance training) and spinal manipulation are effective
      in the short and long term when compared to no treatment. There is also evidence
      that spinal manipulation is effective in the short term when compared to massage
      or placebo spinal manipulation, and weaker evidence when compared to spinal
      mobilization. There is weaker evidence that spinal mobilization is more effective
      in the short term than cold packs in the treatment of post-traumatic headache.
      REVIEWERS' CONCLUSIONS: A few non-invasive physical treatments may be effective
      as prophylactic treatments for chronic/recurrent headaches. Based on trial
      results, these treatments appear to be associated with little risk of serious
      adverse effects. The clinical effectiveness and cost-effectiveness of non
      invasive physical treatments require further research using scientifically
      rigorous methods. The heterogeneity of the studies included in this review means
      that the results of a few additional high-quality trials in the future could
      easily change the conclusions of our review.

PMID- 15266459
TI  - Nasal decongestants for the common cold.
AB  - BACKGROUND: The common cold is a major and recurrent cause of morbidity,
      affecting children and adults two or more times each year. Nasal congestion is
      its commonest symptom and many therapies are marketed for its relief. There is no
      meta-analysis of controlled clinical trials on the effects of nasal decongestants
      in the common cold. OBJECTIVES: To assess the efficacy of nasal decongestants at
      reducing the symptom of nasal congestion in adults and children with the common
      cold and to identify possible adverse effects associated with their use. SEARCH
      STRATEGY: In updating this review in 2004, the following databases were searched:
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections
      Group's specialised register; MEDLINE (January 1996 to February week 1 2004);
      EMBASE (1996 to February week 7 2004); and Current Contents (February 2004). We
      handsearched review citations from other references and contacted known principal
      investigators and pharmaceutical companies. SELECTION CRITERIA: Randomised
      controlled trials with placebo of single-active oral and topical nasal
      decongestants in adults and children suffering from common cold. DATA COLLECTION
      AND ANALYSIS: Data were independently extracted by two reviewers (DT and GJL).
      All outcomes variables were continuous. Subjective outcomes were normalised to a
      common scale and a weighted mean difference (WMD) was calculated. We calculated a
      standardised mean difference (SMD) for the objective outcomes. MAIN RESULTS: Five
      studies involving 286 adults were included, none in children. There was a
      significant 13% decrease in subjective symptoms after decongestants were compared
      with placebo. This was supported by a significant decrease in nasal airways
      resistance. Repeated doses of nasal decongestant were not significantly better
      than placebo at relieving symptoms of nasal congestion. REVIEWERS' CONCLUSIONS: A
      single dose of nasal decongestant in the common cold is moderately effective for
      the short term relief of congestion in adults, while there is no evidence
      available to show benefit after repeated use over several days. There is
      insufficient data on the use of these medications in children and therefore they
      are not recommended for use in young children with the common cold.

PMID- 15266460
TI  - Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically
      ill patients.
AB  - BACKGROUND: Hypertonic solutions are considered to have a greater ability to
      expand blood volume and thus elevate blood pressure and can be administered as a
      small volume infusion over a short time period. On the other hand, the use of
      hypertonic solutions for volume replacement may also have important
      disadvantages. OBJECTIVES: To determine whether hypertonic crystalloid decreases
      mortality in patients with hypovolaemia. SEARCH STRATEGY: We searched MEDLINE,
      EMBASE, The Cochrane Controlled Trials Register and the specialised register of
      the Cochrane Injuries Group. We checked reference lists of all articles
      identified and searched the National Research Register. SELECTION CRITERIA:
      Randomised trials comparing hypertonic to isotonic and near isotonic crystalloid
      in patients with trauma, burns or undergoing surgery. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted the data and assessed the quality
      of the trials. MAIN RESULTS: Fourteen trials with a total of 956 participants are
      included in the meta-analysis. The pooled relative risk (RR) for death in trauma
      patients was 0.84 (95% confidence interval [CI] 0.69-1.04); in patients with
      burns 1.49 (95% CI 0.56-3.95); and in patients undergoing surgery 0.51 (95% CI
      0.09, 2.73). In the one trial that gave data on disability using the Glasgow
      outcome scale, the relative risk for a poor outcome was 1.00 (95% CI 0.82, 1.22).
      REVIEWERS' CONCLUSIONS: This review does not give us enough data to be able to
      say whether hypertonic crystalloid is better than isotonic and near isotonic
      crystalloid for the resuscitation of patients with trauma, burns, or those
      undergoing surgery. However, the confidence intervals are wide and do not exclude
      clinically significant differences. Further trials which clearly state the type
      and amount of fluid used and that are large enough to detect a clinically
      important difference are needed.

PMID- 15266461
TI  - Low level laser therapy (Classes I, II and III) for treating osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) affects a large proportion of the population. Low
      Level Laser Therapy (LLLT) is a light source that generates extremely pure light,
      of a single wavelength. The effect is not thermal, but rather related to
      photochemical reactions in the cells. LLLT was introduced as an alternative non
      invasive treatment for OA about 20 years ago, but its effectiveness is still
      controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment
      of OA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Musculoskeletal
      registry, the registry of the Rehabilitation and Related Therapies field and the
      Cochrane Controlled Trials Register up to January 30, 2004. SELECTION CRITERIA:
      Following an a priori protocol, only controlled clinical trials of LLLT for the
      treatment of patients with a clinical diagnosis of OA were eligible. Abstracts
      were excluded unless further data could be obtained from the authors. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected trials and
      abstracted data using predetermined forms. Heterogeneity was tested with
      Cochran's Q test. A fixed effects model was used throughout for continuous
      variables, except where heterogeneity existed, in which case, a random effects
      model was used. Results were analyzed as weighted mean differences (WMD) with 95%
      confidence intervals (CI), where the difference between the treated and control
      groups was weighted by the inverse of the variance. Standardized mean differences
      (SMD) were calculated by dividing the difference between treated and control by
      the baseline variance. SMD were used when different scales were used to measure
      the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds
      ratios. MAIN RESULTS: Seven trials were included, with 184 patients randomized to
      laser, 161 patients to placebo laser. Treatment duration ranged from 4 to 12
      weeks. Pain was assessed by four trials. The pooled estimate (random effects) of
      three trials showed no effect on pain measured using a scale (SMD: -0.2, 95% CI: 
      1.0, +0.6), but there was statistically significant heterogeneity (p>0,05). Three
      of the trials showed no effect and two demonstrated very beneficial effects with
      laser. In another trial, with no scale-based pain outcome, significantly more
      patients reported pain relief (yes/no) with laser with an odds ratio of 0.05,
      (95% CI: 0.0 to 1.56). Only one study found significant results for increased
      knee range of motion (WMD: -10.62 degrees, 95% CI: -14.07,-7.17). Other outcomes
      of joint tenderness and strength were not significant. Lower dosage of LLLT was
      found as effective than higher dosage for reducing pain and improving knee range
      of motion. REVIEWERS' CONCLUSIONS: For OA, the results are conflicting in
      different studies and may depend on the method of application and other features
      of the LLLT application. Clinicians and researchers should consistently report
      the characteristics of the LLLT device and the application techniques used. New
      trials on LLLT should make use of standardized, validated outcomes. Despite some
      positive findings, this meta-analysis lacked data on how LLLT effectiveness is
      affected by four important factors: wavelength, treatment duration of LLLT,
      dosage and site of application over nerves instead of joints. There is clearly a
      need to investigate the effects of these factors on LLLT effectiveness for OA in
      randomized controlled clinical trials.

PMID- 15266462
TI  - Proton pump inhibitor treatment for acute peptic ulcer bleeding.
AB  - BACKGROUND: Peptic ulcer (PU) bleeding is associated with substantial morbidity,
      mortality and healthcare cost. Randomised controlled trials (RCTs) evaluating the
      clinical effect of proton pump inhibitors (PPIs) in peptic ulcer bleeding have
      yielded conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in the
      management of acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY:
      We performed a search of CENTRAL, The Cochrane Library (Issue 3, 2003), MEDLINE
      (1966 to February 2003) and EMBASE (1980 to February 2003) and proceedings of
      recent major meetings through to February 2003. We searched the reference lists
      of articles and contacted pharmaceutical companies and experts in the field for
      additional published or unpublished data. SELECTION CRITERIA: RCTs of PPI
      treatment (oral or intravenous) compared with either placebo or H(2)-receptor
      antagonist (H(2)RA) in patients with acute bleeding from PU were included if they
      met pre-defined criteria. DATA COLLECTION AND ANALYSIS: Two reviewers extracted
      data independently on a purpose-designed data extraction form. Validity of
      included studies was assessed by adequacy of randomisation method and other pre
      defined criteria. Studies were summarised and meta-analysis was undertaken. The
      influence of factors on the outcomes was assessed. MAIN RESULTS: Twenty-one RCTs
      with a total of 2915 participants were included. Statistical heterogeneity was
      found among trials for rebleeding (P = 0.05), but not for mortality (P = 0.26) or
      surgery (P = 0.42). There was no significant difference in mortality rates
      between PPI and control treatment; pooled rates were 5.2% on PPI versus 4.6% on
      control (odds ratio (OR) 1.11; 95% CI 0.79 to 1.57). PPI treatment significantly
      reduced rates of surgical intervention compared with control; pooled rates were
      8.4% on PPI versus 13.0% on control (OR 0.59; 95% CI 0.46 to 0.76). PPIs
      significantly reduced rebleeding compared to control; pooled rates were 10.6%
      with PPI (range: 0% to 24.4%) versus 18.7% with control treatment (range: 2.3% to
      39.1%), the OR was 0.46 (95% CI 0.33 to 0.64). Results on mortality and
      rebleeding rates were independent of route of PPI administration, type of control
      treatment or application of initial endoscopic haemostatic treatment. Surgical
      intervention rates varied with type of control (PPI significantly reduced
      surgical intervention rates compared with placebo and not when compared with
      H(2)RA) but not with route of PPI administration or application of initial
      endoscopic haemostatic treatment. REVIEWERS' CONCLUSIONS: PPI treatment in PU
      bleeding reduces rebleeding and surgical intervention rates in studies comparing
      treatment with placebo or H(2)RA, but there is no evidence of an effect on
      mortality.

PMID- 15266463
TI  - Spinal manipulation for primary and secondary dysmenorrhoea.
AB  - BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of
      uterine origin and is a common gynaecological condition. One possible treatment
      is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in
      certain vertebrae causes decreased spinal mobility. This could affect the
      sympathetic nerve supply to the blood vessels supplying the pelvic viscera,
      leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these
      vertebrae increases spinal mobility and may improve pelvic blood supply. Another
      hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal
      structures that share the same pelvic nerve pathways. The character of pain from
      musculoskeletal dysfunction can be very similar to gynaecological pain and can
      present as cyclic pain as it can also be altered by hormonal influences
      associated with menstruation. OBJECTIVES: To determine the safety and efficacy of
      spinal manipulative interventions for the treatment of primary or secondary
      dysmenorrhoea when compared to each other, placebo, no treatment, or other
      medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders
      and Subfertility Group trials register (searched 18 March 2004), CENTRAL (The
      Cochrane Library Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to
      March 2004), CINAHL (1982 to March 2004), AMED (1985 to March 2004), Biological
      Abstracts (1969 to Dec 2003), PsycINFO (1872 to March 2004) and SPORTDiscus (1830
      to March 2004). The Cochrane Complementary Medicine Field's Register of
      controlled trials (CISCOM) was also searched. Attempts were also made to identify
      trials from the metaRegister of Controlled Trials and the citation lists of
      review articles and included trials. In most cases, the first or corresponding
      author of each included trial was contacted for additional information. SELECTION
      CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative
      interventions (e.g. chiropractic, osteopathy or manipulative physiotherapy) vs
      each other, placebo, no treatment, or other medical treatment were considered.
      Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from
      an IUD. DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude
      manipulation (HVLA), and one of the Toftness manipulation technique were
      included. Quality assessment and data extraction were performed independently by
      two reviewers. Meta analysis was performed using odds ratios for dichotomous
      outcomes and weighted mean differences for continuous outcomes. Data unsuitable
      for meta-analysis were reported as descriptive data and were also included for
      discussion. The outcome measures were pain relief or pain intensity (dichotomous,
      visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results
      from the four trials of high velocity, low amplitude manipulation suggest that
      the technique was no more effective than sham manipulation for the treatment of
      dysmenorrhoea, although it was possibly more effective than no treatment. Three
      of the smaller trials indicated a difference in favour of HVLA, however the one
      trial with an adequate sample size found no difference between HVLA and sham
      treatment. There was no difference in adverse effects experienced by participants
      in the HVLA or sham treatment. The Toftness technique was shown to be more
      effective than sham treatment by one small trial, but no strong conclusions could
      be made due to the small size of the trial and other methodological
      considerations. REVIEWERS' CONCLUSIONS: Overall there is no evidence to suggest
      that spinal manipulation is effective in the treatment of primary and secondary
      dysmenorrhoea. There is no greater risk of adverse effects with spinal
      manipulation than there is with sham manipulation.

PMID- 15266464
TI  - Surgical treatment for tubal disease in women due to undergo in vitro
      fertilisation.
AB  - BACKGROUND: Tubal disease, and particularly hydrosalpinx, has a detrimental
      effect on the outcome of in-vitro fertilisation (IVF). It has been less clear
      whether surgical intervention for tubal disease prior to IVF is effective in
      improving the likelihood of successful outcome. Most data are retrospective or
      poorly controlled. To date no single prospective randomised trial has shown a
      significant benefit from such surgical treatment prior to IVF. OBJECTIVES: To
      assess the value of surgical treatment for tubal disease prior to IVF. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group
      trials register (10 March 2004), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 1, 2004), MEDLINE (January 1966 to
      February 2004), EMBASE (January 1985 to February 2004), reference lists of
      articles and contacted researchers in the field. SELECTION CRITERIA: All trials
      comparing a surgical treatment for tubal disease with a control group generated
      by randomisation were considered for inclusion in the review. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and extracted data.
      Study authors were contacted for additional information. The studied outcomes
      were live birth (and ongoing pregnancy), pregnancy, ectopic pregnancy,
      miscarriage, multiple pregnancy and complications. MAIN RESULTS: Three randomised
      controlled trials involving 295 (or couples) were included in this review. The
      odds of ongoing pregnancy and live birth (Peto odds ratio (OR) 2.13, 95%
      confidence interval (CI) 1.24 to 3.65) were increased with laparoscopic
      salpingectomy for hydrosalpinges prior to IVF. The odds of pregnancy were also
      increased (Peto odds ratio (OR )1.75, 95%CI 1.07 to 2.86). There was no
      significant difference in the odds of ectopic pregnancy (Peto OR 0.42, 95%CI 0.08
      to 2.14), miscarriage (Peto OR 0.49, 95%CI 0.16 to 1.52) or treatment
      complications (Peto OR 5.80, 95%CI 0.35 to 96.79). No data were available
      concerning the odds of multiple pregnancy. REVIEWERS' CONCLUSIONS: Laparoscopic
      salpingectomy should be considered for all women with hydrosalpinges prior to IVF
      treatment. Currently unilateral salpingectomy for a unilateral hydrosalpinx
      (bilateral salpingectomy for bilateral hydrosalpinges) should be recommended,
      although this requires further evaluation. Further randomised trials are required
      to assess other surgical treatments for hydrosalpinx, such as salpingostomy,
      tubal occlusion or needle drainage of a hydrosalpinx at oocyte retrieval. The
      role of surgery for tubal disease in the absence of a hydrosalpinx is unclear and
      merits further evaluation.

PMID- 15266465
TI  - Buprenorphine maintenance versus placebo or methadone maintenance for opioid
      dependence.
AB  - BACKGROUND: Buprenorphine has recently been reported to be an alternative to
      methadone and LAAM for maintenance treatment of opioid dependent individuals,
      differing results are reported concerning its relative effectiveness indicating
      the need for an integrative review. OBJECTIVES: To evaluate the effects of
      buprenorphine maintenance against placebo and methadone maintenance in retaining
      patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We
      searched the following databases up to 2001, inclusive: Cochrane Drugs and
      Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE,
      EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol
      and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug
      Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on
      Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network
      (ABN), and Library of Congress databases, available NIDA monographs and the
      College on Problems of Drug Dependence Inc. proceedings, the reference lists of
      all identified studies and published reviews and authors of identified RCT's were
      asked about any other published or unpublished relevant RCT. SELECTION CRITERIA:
      Randomised clinical trials of buprenorphine maintenance compared with either
      placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND
      ANALYSIS: Reviewers evaluated the papers separately and independently, rating
      methodological quality of concealment of allocation; data were extracted
      independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen
      studies met the inclusion criteria, all were randomised clinical trials, all but
      one were double-blind. The method of concealment of allocation was not clearly
      described in 11 of the studies, otherwise methodological quality was good.
      Buprenorphine given in flexible doses appeared statistically significantly less
      effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI:
      0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High
      dose buprenorphine does not retain more patients than low dose methadone, but may
      suppress heroin use better. There was no advantage for high dose buprenorphine
      over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose
      buprenorphine was inferior in suppression of heroin use. Buprenorphine was
      statistically significantly superior to placebo medication in retention of
      patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses
      (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88).
      However, only high and very high dose buprenorphine suppressed heroin use
      significantly above placebo. REVIEWERS' CONCLUSIONS: Buprenorphine is an
      effective intervention for use in the maintenance treatment of heroin dependence,
      but it is not more effective than methadone at adequate dosages.

PMID- 15266466
TI  - Air versus oxygen for resuscitation of infants at birth.
AB  - BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of
      infants at birth. There is growing evidence from both animal and human studies
      that room air is as effective as 100% oxygen and that 100% oxygen may have
      adverse effects on breathing physiology and cerebral circulation. There is also
      the theoretical risk of tissue damage due to free oxygen radicals when 100%
      oxygen is given. The use of room air has, therefore, been suggested as a safer
      and possibly more effective alternative. OBJECTIVES: In newborn infants requiring
      resuscitation, does the use of room air reduce the incidence of death,
      neurological disability and short term morbidity when compared with the use of
      100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of
      Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and
      handsearches of reference lists of relevant articles and conference proceedings.
      SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use
      of room air or any other concentration of oxygen versus 100% oxygen in the
      resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors
      assessed the methodological quality of eligible trials and extracted data
      independently. When appropriate, meta-analysis was conducted to provide a pooled
      estimate of effect. For categorical data the relative risk (RR), risk difference
      (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were
      calculated. Continuous data were analysed using weighted mean difference (WMD).
      MAIN RESULTS: Five studies were identified which enrolled a total of 1302
      infants. In two studies allocation was randomised and the caregivers were blinded
      to intervention group. In the other three studies, allocation was quasi
      randomised and the caregivers were not blinded. Pooled analysis of the four
      trials reporting effect on death showed a significant reduction in the rate of
      death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94),
      typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant
      differences between the groups with respect to rates of grade 2 or 3 hypoxic
      ischaemic encephalopathy. One of the four trials reported a statistically
      significant difference in median 5 minute Apgar scores, favouring the group
      allocated to room air. However, the absolute difference between the medians was
      small and there were no significant differences in the median 10 minute Apgar
      scores in the three trials reporting this outcome. One trial followed up a
      selected subgroup of survivors to 18-24 months. There were no significant
      differences in rates of adverse neurodevelopmental outcomes including cerebral
      palsy and failure to achieve various milestones; however, the proportion of
      eligible patients seen was less than 70%. Analyses that were planned for this
      review, but not able to be carried out because of lack of published data,
      included a sub-analysis stratified by gestational age and assessments of the
      effect on bronchopulmonary dysplasia and retinopathy of prematurity. REVIEWERS'
      CONCLUSIONS: There is insufficient evidence at present on which to recommend a
      policy of using room air over 100% oxygen, or vice versa, for newborn
      resuscitation. A reduction in mortality has been seen in infants resuscitated
      with room air, and no evidence of harm has been demonstrated. However, the small
      number of identified studies and their methodologic limitations dictate caution
      in interpreting and applying these results. We note the use of back-up 100%
      oxygen in more than a quarter of infants randomised to room air. Therefore, on
      the basis of currently available evidence, if one chooses room air as the initial
      gas for resuscitation, supplementary oxygen should continue to be made available.

PMID- 15266467
TI  - Psychological interventions for non-ulcer dyspepsia.
AB  - BACKGROUND: Studies have also shown that NUD patients have higher scores of
      anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and
      tendency to be more pessimistic when compared with the community controls.
      However, the role of psychological interventions in NUD remains uncertain.
      OBJECTIVES: This review aims to determine the effectiveness of psychological
      interventions including psychotherapy, psychodrama, cognitive behavioral therapy,
      relaxation therapy and hypnosis in the improvement of either individual or global
      dyspepsia symptom scores and quality of life scores patients with NUD. SEARCH
      STRATEGY: Trials were located through electronic searches of the Cochrane
      Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using
      very broad subject headings and text words. Bibliographies of retrieved articles
      were also searched and experts in the field were contacted. SELECTION CRITERIA:
      All randomised controlled trials (RCTs) or quasi-randomised studies assessing the
      effectiveness of psychological interventions (including psychotherapy,
      psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for
      non-ulcer dyspepsia (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data
      collected included individual, global dyspepsia symptom scores and quality of
      life (QoL) scores. MAIN RESULTS: We identified only four trials, each using
      different psychological interventions and three presenting results in a manner,
      that did not allow synthesis of the data to form a meta-analysis. All trials
      suggest that psychological interventions benefit dyspepsia symptoms and this
      effect persists for one year. However, all trials use statistical techniques that
      adjusted for baseline differences between groups. This should not be necessary
      for a randomised trial that is adequately powered suggesting that the sample size
      of these papers was too small. Unadjusted data was not statistically significant.
      The other problem of psychological intervention include low recruitment and high
      drop out rate which has been shown to be greater in patients receiving group
      therapy. REVIEWERS' CONCLUSIONS: There is currently insufficient evidence from
      this review to confirm the efficacy of psychological intervention in NUD. There
      is also no evidence on the combined effects of pharmacological and psychological
      therapy. Nevertheless, if there are any benefits of psychological therapies, they
      are likely to persist long-term and NUD is a chronic relapsing and remitting
      disorder. Psychological therapies may therefore be offered to patients with
      severe symptoms that have not responded to pharmacological therapies.

PMID- 15266468
TI  - Scopolamine for preventing and treating motion sickness.
AB  - BACKGROUND: Motion sickness - the discomfort experienced when perceived motion
      disturbs the organs of balance - may include symptoms such as nausea, vomiting,
      pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control
      and prevention of these symptoms have included pharmacological, behavioural and
      complementary therapies. Although scopolamine has been used in the treatment and
      prevention of motion sickness for decades, there have been no systematic reviews
      of its effectiveness. OBJECTIVES: To assess the effectiveness of scopolamine
      versus no therapy, placebo, other drugs, behavioural and complementary therapy or
      two or more of the above therapies in combination for motion sickness in persons
      (both adults and children) without known vestibular, visual or central nervous
      system pathology. SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders
      Group Specialised Register, the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 4, 2003), MEDLINE (OVID, 1966 to March Week 1 2004),
      EMBASE (1974 to 2004) CINAHL (Ovid, 1982 to March Week 1 2004) and reference
      lists of retrieved studies were searched for relevant studies. No language
      restrictions were applied. SELECTION CRITERIA: All parallel-arm, randomised
      controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo,
      other drugs, behavioural and complementary therapy or two or more of the above
      therapies in combination were included. Outcomes relating to the prevention of
      onset or treatment of clinically-defined motion sickness, task ability and
      psychological tests, changes in physiological parameters and adverse effects were
      considered. DATA COLLECTION AND ANALYSIS: Data from the studies were extracted
      independently by two authors using standardised forms. Study quality was
      assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was
      calculated using the random effects model. MAIN RESULTS: Of 27 studies considered
      potentially relevant, 12 studies enrolling 901 subjects met the entry criteria.
      Scopolamine was administered via transdermal patches, tablets or capsules, oral
      solutions or intravenously. Scopolamine was compared against placebo, calcium
      channel antagonists, antihistamine, meth-scopolamine or a combination of
      scopolamine and ephedrine. Studies were generally small in size and of varying
      quality. Scopolamine was more effective than placebo in the prevention of
      symptoms. Comparisons between scopolamine and other agents were few and suggested
      that scopolamine was superior (versus meth-scopolamine) or equivalent (versus
      antihistamines) as a preventative agent. Evidence comparing scopolamine to
      cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal.
      Although sample sizes were small, scopolamine was no more likely to induce
      drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth
      was more likely with scopolamine than with meth-scopolamine or cinnarizine. No
      studies were available relating to the therapeutic effectiveness of scopolamine
      in the management of established symptoms of motion sickness. REVIEWERS'
      CONCLUSIONS: The use of scopolamine versus placebo in preventing motion sickness
      has been shown to be effective. No conclusions can be made on the comparative
      effectiveness of scopolamine and other agents such as antihistamines and calcium
      channel antagonists. In addition, no randomised controlled trials were identified
      that examined the effectiveness of scopolamine in the treatment of established
      symptoms of motion sickness.

PMID- 15266469
TI  - Enhancing partner support to improve smoking cessation.
AB  - BACKGROUND: While many cessation programs are available to assist smokers in
      quitting, research suggests that partner involvement may encourage long-term
      abstinence. OBJECTIVES: The purpose of this review was to determine if an
      intervention to enhance partner support helps smoking cessation when added as an
      adjunct to a smoking cessation program. SEARCH STRATEGY: The search was performed
      in: Cochrane Tobacco Addiction Group specialized register (Apr 2004), Cochrane
      controlled trials register (Apr 2004), CDC and Prevention-Tobacco Information and
      Prevention Database (Jul 2000), MEDLINE (1966-Apr 2004), Cancer Lit (1966-Apr
      2004), EMBASE (1974-Apr 2004), CINAHL (1966-Jul 2000), PsycInfo (1861-Apr 2004),
      ERIC, PsycLit, & Dissertation Abstracts (1861-Dec 1999), SSCI (1972-Apr 2004) and
      HealthStar (1975-Jul 2000). The search terms used were smoking (prevention,
      control, therapy), smoking cessation, and support (family, marriage, spouse,
      partner, sexual partner, buddy, friend, co-habitees, and co-worker). The search
      was also limited to English language. SELECTION CRITERIA: Randomized controlled
      trials of smoking cessation interventions that compared an intervention that
      included a partner support component with an otherwise identical intervention and
      reported follow-up of 6 months or greater. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently identified the included studies and extracted data using
      a structured form. A third reviewer was consulted to aid in the resolution of
      discrepancies. Abstinence and biochemical assessment were the primary outcome
      measures and were analyzed at two post-treatment intervals: 6-9 months and >12
      months. The scores of PIQ (partner interaction questionnaire) were also analyzed
      to assess partner support. A fixed-effects model was used to assess the summary
      effect of the studies. MAIN RESULTS: A total of 40 articles were identified for
      this review. Only eight articles (nine studies) met the inclusion criteria. The
      definition of partner varied among the studies. All studies included data on self
      reported smoking cessation rates, but there was limited biochemical validation of
      abstinence rates. The odds ratio for self-reported abstinence at 6-9 months was
      1.08 (CI 95%, 0.81 -1.44); and at 12 months post-treatment was 1.0 (CI 95%, 0.75 
      1.34). Of the six studies that measured partner support at follow-up, only two
      studies reported significant increase in partner support in the intervention
      groups. REVIEWERS' CONCLUSIONS: In this review of the randomized controlled
      trials of interventions designed to enhance partner support for smokers in
      cessation programs, we failed to detect an increase in quit rates. Limited data
      from several of the trials suggest that these interventions did not increase
      partner support either. No conclusions can be made about the impact of partner
      support on smoking cessation. More systematic intervention to affect partnership
      significantly should be delivered if partner support were part of an existing
      cessation program.

PMID- 15266470
TI  - Early surfactant administration with brief ventilation vs selective surfactant
      and continued mechanical ventilation for preterm infants with or at risk for
      respiratory distress syndrome.
AB  - BACKGROUND: Both prophylactic and early surfactant replacement therapy, compared
      with later selective surfactant administration, reduce mortality and pulmonary
      complications in ventilated infants with respiratory distress syndrome (RDS).
      However, continued post-surfactant intubation and ventilation are risk factors
      for chronic lung disease. Whether prophylactic or early surfactant administration
      followed by prompt extubation, compared with later, selective use of surfactant
      followed by continued mechanical ventilation reduces the need for mechanical
      ventilation and the incidence of chronic lung disease is unknown. OBJECTIVES: To
      compare two treatment strategies in preterm infants with, or at risk for, RDS:
      early surfactant administration with brief mechanical ventilation (less than one
      hour) followed by extubation, vs later, selective surfactant administration,
      continued mechanical ventilation and extubation from low respiratory support. Two
      populations of infants receiving early surfactant were considered: spontaneously
      breathing infants with signs of RDS (surfactant administration during evolution
      of RDS prior to requiring intubation for respiratory failure) and infants at high
      risk for RDS (prophylactic surfactant administration within 15 minutes after
      birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal
      trials, MEDLINE (1966-December 2003), CINAHL (1982-December 2003), EMBASE (1980
      December 2003), Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 1, 2004), Pediatric Research (1990-2003), abstracts,
      expert informants and hand searching. No language restrictions were applied.
      SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials
      comparing early surfactant administration with planned brief mechanical
      ventilation (less than one hour) followed by extubation, vs selective surfactant
      administration, continued mechanical ventilation and extubation from low
      respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding
      effects on incidence of mechanical ventilation (ventilation continued or
      initiated beyond one hour after surfactant administration), incidence of
      bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration
      of mechanical ventilation, duration of hospitalization, time in oxygen, duration
      of respiratory support (including CPAP and nasal cannula), number of patients
      receiving surfactant, number of surfactant doses administered per patient,
      incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax),
      patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other
      complications of prematurity. Treatment effect was expressed as relative risk
      (RR) and risk difference (RD) for categorical variables, and weighted mean
      difference (WMD) for continuous variables. MAIN RESULTS: Four randomized
      controlled clinical trials met selection criteria and were included in this
      review. In these studies of infants with signs of RDS, intubation and early
      surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with
      later selective surfactant administration was associated with a lower incidence
      of mechanical ventilation [typical RR 0.70, 95% CI 0.59, 0.84]. None of the
      trials reported a significant difference in the incidence of BPD or CLD; however,
      meta-analysis for this outcome cannot yet be performed because the primary data
      from three of the trials have not yet been published in full. A larger proportion
      of infants in the early surfactant group received surfactant than in the
      selective surfactant group [typical RR 1.59, 95% CI 1.35, 1.88]. The number of
      surfactant doses per patient was significantly greater among patients randomized
      to the early surfactant group [WMD 0.51 doses per patient, 95% CI 0.36, 0.65].
      Trends towards a decreased incidence of air leak syndromes (two studies) and a
      higher incidence of patent ductus arteriosus requiring treatment (one study) were
      seen in the early surfactant group. There was no evidence of effect on time in
      oxygen or duration of mechanical ventilation. REVIEWERS' CONCLUSIONS: Early
      surfactant replacement therapy with extubation to NCPAP compared with later,
      selective surfactant replacement and continued mechanical ventilation with
      extubation from low ventilator support is associated with a reduced need for
      mechanical ventilation and increased utilization of exogenous surfactant therapy.
      There is insufficient evidence at present to reliably evaluate effect on BPD or
      CLD.

PMID- 15266471
TI  - Interventions for replacing missing teeth: maintaining health around dental
      implants.
AB  - BACKGROUND: To maintain healthy tissues around dental implants it is important to
      institute an effective preventive regimen (supportive therapy). Different
      maintenance regimens have been suggested, however it is unclear which are the
      most effective. OBJECTIVES: To test the null hypothesis of no difference between
      different interventions for maintaining healthy tissues around dental implants.
      SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register,
      the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE.
      Handsearching included several dental journals. We checked the bibliographies of
      the identified randomised controlled trials (RCTs) and relevant review articles
      for studies outside the handsearched journals. We wrote to authors of all
      identified RCTs, to more than 55 oral implant manufacturers and an internet
      discussion group to find unpublished or ongoing RCTs. No language restrictions
      were applied. The last electronic search was conducted on 2 February 2004.
      SELECTION CRITERIA: All randomised controlled trials of oral implants comparing
      agents or interventions for maintaining or recovering healthy tissues around
      dental implants. DATA COLLECTION AND ANALYSIS: We carried out a quality
      assessment of the included RCTs in duplicate and contacted the authors for
      missing information. We independently extracted the data in duplicate. We
      followed the Cochrane Oral Health Group's statistical guidelines. MAIN RESULTS:
      Fourteen RCTs were identified. Five of these trials, which reported results from
      a total of 127 patients, were suitable for inclusion in the review. Two trials
      evaluated the efficacy of powered and sonic toothbrushes, respectively, when
      compared to manual toothbrushing and showed no statistically significant
      differences. One RCT compared Listerine versus placebo mouthwashes showing a
      reduction of 54% in plaque and 34% in marginal bleeding compared with the
      placebo. One trial compared self administered subgingival chlorhexidine
      irrigation versus chlorhexidine mouthwash. The group using chlorhexidine
      irrigation resulted in statistically significantly lower mean plaque scores and a
      marginal bleeding index than the group using chlorhexidine mouthwash, however the
      mouthwash was given at a suboptimal dosage. One study compared etching gel with
      mechanical debridement showing no statistical differences. Follow ups ranged
      between 6 weeks and 5 months. It was not possible to make any meta-analysis as
      each trial assessed different interventions. REVIEWERS' CONCLUSIONS: There is
      only little reliable evidence for which are the most effective interventions for
      maintaining health around peri-implant tissues. There was no evidence that the
      use of powered or sonic toothbrushes was superior to manual toothbrushing. There
      is weak evidence that Listerine mouthwash, used twice a day for 30 seconds, as
      adjunct to routine oral hygiene is effective in reducing plaque formation and
      marginal bleeding around implants. There was no evidence that phosphoric etching
      gel offered any clinical advantage over mechanical debridement. These findings
      are based on RCTs having short follow-up periods and few subjects. There is not
      any reliable evidence for the most effective regimens for long term maintenance.
      More RCTs should be conducted in this area. In particular, there is a definite
      need for trials powered to find possible differences, using primary outcome
      measures and with much longer follow up. Such trials should be reported according
      the CONSORT guidelines (http://www.consort-statement.org/).

PMID- 15266472
TI  - Interventions for the treatment of Morton's neuroma.
AB  - BACKGROUND: Morton's neuroma is a common, paroxysmal neuralgia affecting the web
      spaces of the toes, typically the third. The pain is often so debilitating that
      patients become anxious about walking or even putting their foot to the ground.
      Insoles, corticosteroid injections, excision of the nerve, transposition of the
      nerve and neurolysis of the nerve are commonly used treatments. Their
      effectiveness is poorly understood. OBJECTIVES: To examine the evidence from
      randomised controlled trials concerning the effectiveness of interventions in
      adults with Morton's neuroma. SEARCH STRATEGY: We searched the Cochrane
      Neuromuscular Disease Group trials register (searched January 2003), MEDLINE
      (January 1966 to January Week 2 2003), EMBASE (January 1980 to February Week 2
      2003), and CINAHL (January 1982 to February Week 1 2003). SELECTION CRITERIA:
      Randomised or quasi-randomised (methods of allocating participants to an
      intervention which were not strictly random e.g. date of birth, hospital record,
      number alternation) controlled trials of interventions for Morton's neuroma were
      selected. Studies where participants were not randomised into intervention groups
      were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers selected trials for
      inclusion in the review, assessed their methodological quality and extracted data
      independently. MAIN RESULTS: Three trials involving 121 people were included.
      There is, at most, a very limited indication that transposition of the transected
      plantar digital nerve may yield better results than standard resection of the
      nerve in the long term. There is no evidence to support the use of supinatory
      insoles. There are, at best, very limited indications to suggest that dorsal
      incisions for resection of the plantar digital nerve may result in less
      symptomatic post-operative scars when compared to plantar excision of the nerve.
      REVIEWERS' CONCLUSIONS: There is insufficient evidence with which to assess the
      effectiveness of surgical and non-surgical interventions for Morton's neuroma.
      Well designed trials are needed to begin to establish an evidence base for the
      treatment of Morton's neuroma pain.

PMID- 15266473
TI  - Antiplatelet agents and anticoagulants for hypertension.
AB  - BACKGROUND: Although elevated systemic blood pressure results in high
      intravascular pressure, the main complications, coronary heart disease (CHD),
      ischaemic strokes and peripheral vascular disease (PVD), are related to
      thrombosis rather than haemorrhage. Some complications related to elevated blood
      pressure, heart failure or atrial fibrillation, are themselves associated with
      stroke and thromboembolism. It therefore seemed plausible that use of
      antithrombotic therapy may be particularly useful in preventing thrombosis
      related complications of elevated blood pressure. OBJECTIVES: To conduct a
      systematic review of the role of antiplatelet therapy and anticoagulation in
      patients with blood pressure, including those with elevations in both systolic
      and diastolic blood pressure, isolated elevations of either systolic or diastolic
      blood pressure, to address the following hypotheses: (i) antiplatelet agents
      reduce total deaths and/or major thrombotic events when compared to placebo or
      other active treatment; and (ii) oral anticoagulants reduce total deaths and/or
      major thromboembolic events when compared to placebo or other active treatment.
      SEARCH STRATEGY: Reference lists of papers resulting from this search, electronic
      database searching (MEDLINE, EMBASE, DARE), and abstracts from national and
      international cardiovascular meetings were studied to identify unpublished
      studies. Relevant authors of these studies were contacted to obtain further data.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with elevated
      blood pressure were included if they were of at least 3 months in duration and
      compared antithrombotic therapy with control or other active treatment. DATA
      COLLECTION AND ANALYSIS: Data were independently collected and verified by two
      reviewers. Data from different trials were pooled where appropriate. MAIN
      RESULTS: The ATC meta-analysis of antiplatelet therapy for secondary prevention
      in patients with elevated blood pressure reported an absolute reduction in
      vascular events of 4.1% as compared to placebo. Data on the patients with
      elevated blood pressure from the 29 individual trials included in this meta
      analysis was requested but could not be obtained. Three additional trials met the
      inclusion criteria and are reported on here. Acetylsalicylic acid (ASA) did not
      reduce stroke or 'all cardiovascular events' compared to placebo in primary
      prevention patients with elevated blood pressure and no prior cardiovascular
      disease. Based on one large trial (HOT trial), ASA taken for 5 years reduced
      myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major
      haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or
      cardiovascular mortality. There was no significant difference between ASA and
      clopidogrel for the composite endpoint of stroke, myocardial infarction or
      vascular death in one trial (CAPRIE 1996). In two small trials warfarin alone or
      in combination with ASA did not reduce stroke or coronary events. REVIEWERS'
      CONCLUSIONS: For primary prevention in patients with elevated blood pressure,
      anti-platelet therapy with ASA cannot be recommended since the magnitude of
      benefit, a reduction in myocardial infarction, is negated by a harm of similar
      magnitude, an increase in major haemorrhage. For secondary prevention in patients
      with elevated blood pressure (ATC meta-analysis: APTC 1994) antiplatelet therapy
      is recommended because the magnitude of the absolute benefit is many times
      greater. Warfarin therapy alone or in combination with aspirin in patients with
      elevated blood pressure cannot be recommended because of lack of demonstrated
      benefit. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel
      have not been sufficiently evaluated in patients with elevated blood pressure.
      Further trials of antithrombotic therapy with complete documentation of all
      benefits and harms are required in patients with elevated blood pressure.

PMID- 15266474
TI  - Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of
      malignant lymphoma.
AB  - BACKGROUND: Granulopoiesis-stimulating factors, such as granulocyte-colony
      stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor
      (GM-CSF), are being used to prevent febrile neutropenia and infection in patients
      undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM
      CSF improve dose intensity, tumour response, and overall survival in this patient
      population has not been answered yet. Since the results from single studies are
      inconclusive, a systematic review was undertaken. OBJECTIVES: To determine the
      effectiveness of G-CSF and GM-CSF in patients with malignant lymphoma with
      respect to preventing neutropenia, febrile neutropenia and infection; improving
      quality of life, adherence to treatment protocol, tumour response, freedom from
      treatment failure (FFTF) and overall survival (OS); and adverse effects. SEARCH
      STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, CancerLit, and other
      relevant literature databases; internet databases of ongoing trials; and
      conference proceedings of the American Society of Clinical Oncology and the
      American Society of Hematology (1980 - 2003). We included full-text and abstract
      publications as well as unpublished data. SELECTION CRITERIA: Randomised
      controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no
      prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy
      were included for review. Both study arms had to receive identical chemotherapy
      and supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality
      assessment, data extraction and analysis were done in duplicate. Authors were
      contacted to obtain missing data. MAIN RESULTS: We included 12 eligible
      randomised controlled trials with 1823 patients. Compared with no prophylaxis,
      both G-CSF and GM-CSF significantly reduced the relative risk (RR) for severe
      neutropenia (RR 0.67; 95% confidence interval (CI) 0.60 to 0.73), febrile
      neutropenia (RR 0.74; 95% CI 0.62 to 0.89) and infection (RR 0.74; 95% CI 0.64 to
      0.85). There was no evidence that either G-CSF or GM-CSF reduced the number of
      patients requiring intravenous antibiotics (RR 0.82; 95%CI 0.57 to 1.18); lowered
      infection related mortality (RR 1.37; 95% CI 0.66 to 2.82); or improved complete
      tumour response (RR 1.02; 95% CI 0.94 to 1.11), FFTF (hazard ratio 1.11; 95% CI
      0.91 to 1.35) and OS (hazard ratio 1.00; 95% CI 0.86 to 1.16). One study
      evaluated quality of life parameters and found no differences between the
      treatment groups. REVIEWERS' CONCLUSIONS: G-CSF and GM-CSF, when used as a
      prophylaxis in patients with malignant lymphoma undergoing conventional
      chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection.
      However, based on the randomised trials currently available, there is no evidence
      that either G-CSF or GM-CSF provide a significant advantage in terms of complete
      tumour response, FFTF or OS.

PMID- 15266475
TI  - Exercise therapy for chronic fatigue syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is an illness characterised by
      persistent medically unexplained fatigue. CFS is a serious health-care problem
      with a prevalence of up to 3%. Treatment strategies for CFS include
      psychological, physical and pharmacological interventions. OBJECTIVES: To
      investigate the relative effectiveness of exercise therapy and control treatments
      for CFS. SEARCH STRATEGY: CCDANCTR-Studies and CENTRAL were searched using
      "Chronic Fatigue" and Exercise. The Journal of Chronic Fatigue Syndrome and CFS
      conferences were handsearched. Experts in the field were contacted.
      Clinicaltrials.gov and controlled-trials.com were searched. SELECTION CRITERIA:
      Only Randomised Controlled Trials (RCT) including participants with a clinical
      diagnosis of CFS and of any age were included. DATA COLLECTION AND ANALYSIS: The
      full articles of studies identified were inspected by two reviewers (ME and HMG).
      Continuous measures of outcome were combined using standardised mean differences.
      An overall effect size was calculated for each outcome with 95% confidence
      intervals. One sensitivity analysis was undertaken to test the robustness of the
      results. MAIN RESULTS: Nine studies were identified for possible inclusion in
      this review, and five of those studies were included. At 12 weeks, those
      receiving exercise therapy were less fatigued than the control participants (SMD 
      0.77, 95% CIs -1.26 to -0.28). Physical functioning was significantly improved
      with exercise therapy group (SMD -0.64, CIs -0.96 to -0.33) but there were more
      dropouts with exercise therapy (RR 1.73, CIs 0.92 to 3.24). Depression was non
      significantly improved in the exercise therapy group compared to the control
      group at 12 weeks (WMD -0.58, 95% CIs -2.08 to 0.92). Participants receiving
      exercise therapy were less fatigued than those receiving the antidepressant
      fluoxetine at 12 weeks (WMD -1.24, 95% CIs -5.31 to 2.83). Participants receiving
      the combination of the two interventions, exercise + fluoxetine, were less
      fatigued than those receiving exercise therapy alone at 12 weeks, although again
      the difference did not reach significance (WMD 3.74, 95% CIs -2.16 to 9.64). When
      exercise therapy was combined with patient education, those receiving the
      combination were less fatigued than those receiving exercise therapy alone at 12
      weeks (WMD 0.70, 95% CIs -1.48 to 2.88). REVIEWERS' CONCLUSIONS: There is
      encouraging evidence that some patients may benefit from exercise therapy and no
      evidence that exercise therapy may worsen outcomes on average. However the
      treatment may be less acceptable to patients than other management approaches,
      such as rest or pacing. Patients with CFS who are similar to those in these
      trials should be offered exercise therapy, and their progress monitored Further
      high quality randomised studies are needed.

PMID- 15266476
TI  - Anticonvulsant drugs for migraine prophylaxis.
AB  - BACKGROUND: Anticonvulsant drugs seem to be useful in clinical practice for the
      prophylaxis of migraine. This might be explained by a variety of actions of these
      drugs in the central nervous system that are probably relevant to the
      pathophysiology of migraine. OBJECTIVES: To describe and assess the evidence from
      controlled trials on the efficacy and tolerability of anticonvulsants for
      preventing migraine attacks in adult patients with migraine. SEARCH STRATEGY: We
      searched MEDLINE (from 1966 on) and the Cochrane Central Register of Controlled
      Trials (CENTRAL). Date of most recent search: April 2003. Additional information
      was gained from hand-searching specialist headache journals; correspondence with
      pharmaceutical companies, authors of reports, and experts in the field; and a
      wide variety of review articles and book chapters. SELECTION CRITERIA: Studies
      were required to be prospective, controlled trials of self-administered drug
      treatments taken regularly to prevent the occurrence of migraine attacks and/or
      to reduce the intensity of those attacks. DATA COLLECTION AND ANALYSIS: Studies
      were selected and data extracted by two independent reviewers. For migraine
      frequency data, standardized mean differences (SMDs) were calculated for
      individual studies and pooled across studies. For dichotomous data on significant
      reduction in migraine frequency, odds ratios (ORs) and numbers-needed-to-treat
      (NNTs) were similarly calculated. Adverse events were analyzed by calculating
      numbers-needed-to-harm (NNHs) for studies using similar agents. MAIN RESULTS:
      Fifteen papers were included in the review. Of these, 14 reported trials
      comparing anticonvulsants with placebo, as follows: four trials of divalproex
      sodium, three trials of topiramate, two trials of sodium valproate, two trials of
      gabapentin, and one trial each of carbamazepine, clonazepam, and lamotrigine. One
      paper reported a trial of sodium valproate versus an active comparator,
      flunarizine, and one trial of divalproex sodium versus placebo included a
      comparison against propranolol, also an active comparator. Data from 2024
      patients were considered. Analysis of data from eight trials (n = 841)
      demonstrates that anticonvulsants, considered as a class, reduce migraine
      frequency by about 1.4 attacks per 28 days as compared to placebo (SMD -0.60; 95%
      confidence interval [CI] -0.93 to -0.26). Data from 10 trials (n = 1341) show
      that anticonvulsants, considered as a class, also more than double the number of
      patients for whom migraine frequency is reduced by 50% or more, relative to
      placebo (OR 3.90; 95% CI 2.61 to 5.82; NNT 3.8; 95% CI 3.2 to 4.6). For seven
      trials of sodium valproate and divalproex sodium, NNHs for five clinically
      important adverse events ranged from 6.6 to 16.3. For the three trials of
      topiramate, NNHs for eight adverse events (100-mg dose) ranged from 2.4 to 32.9.
      REVIEWERS' CONCLUSIONS: Anticonvulsants appear to be both effective in reducing
      migraine frequency and reasonably well tolerated. There is noticeable variation
      among individual agents, but there are insufficient data to know whether this is
      due to chance or variation in true efficacy. Neither clonazepam nor lamotrigine
      was superior to placebo (one trial each). Relatively few robust trials are
      available for agents other than sodium valproate/divalproex sodium. Two recently
      published and large trials of topiramate demonstrated reasonable efficacy, and
      one further trial of this agent is anticipated in the near future.

PMID- 15266477
TI  - Anticholinergic agents for chronic asthma in adults.
AB  - BACKGROUND: Anticholinergic agents such as ipratropium bromide are sometimes used
      in the treatment of chronic asthma. They effect bronchodilation and have also
      been used in combination with beta2-agonists in the management of chronic asthma.
      OBJECTIVES: To examine the effectiveness of anticholinergic agents versus placebo
      and in comparison with beta2-agonists or as adjunctive therapy to beta2-agonists.
      SEARCH STRATEGY: The Cochrane Airways Group asthma and wheeze database was
      searched with a pre-defined search strategy. Searches were current as of August
      2003. Reference lists of articles were also examined. SELECTION CRITERIA:
      Randomised trials or quasi-randomised trials were considered for inclusion.
      Studies assessing an anticholinergic agent versus placebo or in
      combination/comparison with beta2-agonists were included. In practice, all beta2
      agonists were short acting. Short-term (less than 24 hours duration) and longer
      term studies were separated; the latter are reported in this review and the
      former in the review, "Anticholinergic agents for chronic asthma in adults short
      term". DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      abstracts for retrieval of full text articles. Papers were then assessed for
      suitability for inclusion in the review. Data from included studies were
      extracted by two reviewers and entered into the software package (RevMan 4.2). We
      contacted authors for missing data and some responded. Adverse effect data were
      analysed if reported in the included studies. MAIN RESULTS: The studies analysed
      were in two groups: those comparing anticholinergics with placebo and those
      comparing the combination of anticholinergics with short acting beta2-agonists
      versus short acting beta2-agonists alone. The former group had 13 studies
      involving 205 participants included in this review, and the latter 9 studies
      involving 440 patients. Generally methodological quality was poorly reported, and
      there were some reservations with respect to the quality of the studies. Despite
      the limited number of studies that could be combined, anticholinergic agents in
      comparison with placebo resulted in more favourable symptom scores particularly
      in respect of daytime dyspnoea (WMD -0.09 (95%CI -0.14, -0.04, 3 studies, 59
      patients). Daily peak flow measurements also showed a statistically significant
      improvement for the anticholinergic (e.g. morning PEF: WMD =14.38 litres/min
      (95%CI 7.69, 21.08; 3 studies, 59 patients). However the clinical significance is
      small and in terms of peak flow measurements equates to approximately a 7%
      increase over placebo. The more clinically relevant comparison of a combination
      of anticholinergic plus short acting beta2-agonist versus short acting beta2
      agonist alone gave no evidence in respect of symptom scores or peak flow rates of
      any significant differences between the two regimes. Again there are reservations
      with respect to the quality of the information from which these conclusions are
      drawn. REVIEWERS' CONCLUSIONS: Overall this review provides no justification for
      routinely introducing anticholinergics as part of add-on treatment for patients
      whose asthma is not well controlled on standard therapies. This does not exclude
      the possibility that there may be a sub-group of patients who derive some benefit
      and a trial of treatment in individual patients may still be justified. The role
      of long term anticholinergics such as tiotropium bromide has yet to be
      established in patients with asthma and any future trials might draw on the
      messages derived from this review.

PMID- 15266478
TI  - Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea
      and vomiting.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) are common complications
      following surgery and anaesthesia. Drug therapy to prevent PONV is only partially
      effective. An alternative approach is to stimulate a P6 acupoint on the wrist.
      Although there are many trials examining this technique, the results are
      conflicting. OBJECTIVES: To determine the efficacy and safety of P6 acupoint
      stimulation in preventing PONV. SEARCH STRATEGY: We searched CENTRAL (The
      Cochrane Library, Issue 1, 2003), MEDLINE (January 1966 to January 2003), EMBASE
      (January 1988 to January 2003) and the National Library of Medicine publication
      list of acupuncture studies up to and including January 2003. Reference lists of
      retrieved papers and reviews were consulted for additional references. SELECTION
      CRITERIA: All randomized trials of techniques that stimulated the P6 acupoint
      compared with: sham treatment or drug therapy for the prevention of PONV.
      Interventions used in these trials included acupuncture, electro-acupuncture,
      transcutaneous nerve stimulation, laser stimulation, acustimulation device and
      acupressure. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      methodological quality and extracted the data. Primary outcomes were incidences
      of nausea and vomiting. Secondary outcomes were the need for rescue antiemetic
      therapy and adverse effects. A random effects model was used and relative risk
      (RR) with associated 95% confidence intervals (95% CI) are reported. Egger's test
      was used to measure the asymmetry of the funnel plot. MAIN RESULTS: Twenty-six
      trials (n = 3347) were included, none of which reported adequate allocation
      concealment. There were significant reductions in the risks of nausea (RR 0.72,
      95% CI 0.59 to 0.89), vomiting (RR 0.71, 95% CI 0.56 to 0.91) and the need for
      rescue antiemetics (RR 0.76, 95% CI 0.58 to 1.00) in the P6 acupoint stimulation
      group compared with the sham treatment, although many of the trials were
      heterogeneous. There was no evidence of difference in the risk of nausea and
      vomiting in the P6 acupoint stimulation group versus individual antiemetic
      groups. However, when different antiemetics were pooled, there was significant
      reduction in the risk of nausea but not vomiting in the P6 acupoint stimulation
      group compared with the antiemetic group (RR 0.70, 95% CI 0.50 to 0.98; RR 0.92,
      95% CI 0.65 to 1.29 respectively). The side effects associated with P6 acupoint
      stimulation were minor. There was some evidence of asymmetry of the funnel plot.
      REVIEWERS' CONCLUSIONS: This systematic review supports the use of P6 acupoint
      stimulation in patients without antiemetic prophylaxis. Compared with antiemetic
      prophylaxis, P6 acupoint stimulation seems to reduce the risk of nausea but not
      vomiting.

PMID- 15266479
TI  - Feeding interventions for growth and development in infants with cleft lip, cleft
      palate or cleft lip and palate.
AB  - BACKGROUND: Cleft lip and cleft palate are common birth defects, affecting about
      one baby of every 700 born. Feeding these babies is an immediate concern and
      there is evidence of delay in growth of children with a cleft as compared to
      those without clefting. In an effort to combat reduced weight for height, a
      variety of advice and devices are recommended to aid feeding of babies with
      clefts. OBJECTIVES: This review aims to assess the effects of these feeding
      interventions in babies with cleft lip and/or palate on growth, development and
      parental satisfaction. SEARCH STRATEGY: We searched the Cochrane Oral Health
      Group's Trials register (June 2001), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to May 24th
      2004), EMBASE (1980 to August 7th 2002), CINAHL (1982 to August 7th 2002),
      PsychINFO (1967 to August 13th 2002), AMED (1985 to August 13th 2002). Attempts
      were made to identify both unpublished and ongoing studies. There was no
      restriction with regard to language of publication. SELECTION CRITERIA: Studies
      were included if they were randomised controlled trials (RCTs) of feeding
      interventions for babies born with cleft lip, cleft palate or cleft lip and
      palate up to the age of 6 months (from term). DATA COLLECTION AND ANALYSIS:
      Studies were assessed for relevance independently and in duplicate. All studies
      meeting the inclusion criteria were data extracted and assessed for validity
      independently by each member of the review team. Authors were contacted for
      clarification or missing information whenever possible. MAIN RESULTS: Four RCTs
      with a total of 232 babies, were included in the review. Comparisons made within
      the RCTs were squeezable versus rigid feeding bottles (two studies),
      breastfeeding versus spoon-feeding (one study) and maxillary plate versus no
      plate (one study). No statistically significant differences were shown for any of
      the primary outcomes when comparing bottle types, although squeezable bottles
      were less likely to require modification. No statistically significant difference
      was shown for infants fitted with a maxillary plate compared to no plate. A
      statistically significant difference in weight (kg) at 6 weeks post-surgery was
      shown in favour of breastfeeding when compared to spoon-feeding (mean difference
      0.47; 95% CI: 0.20, 0.74). REVIEWERS' CONCLUSIONS: Squeezable bottles appear
      easier to use than rigid feeding bottles for babies born with clefts of the lip
      and/or palate, however, there is no evidence of a difference in growth outcomes
      between the bottle types. There is weak evidence that babies should be breastfed
      rather than spoon-fed following surgery for cleft lip. No evidence was found to
      assess the use of any types of maternal advice and/or support for these babies.

PMID- 15266480
TI  - Exercise based rehabilitation for heart failure.
AB  - BACKGROUND: The prevalence of chronic heart failure is increasing, and increases
      with increasing age. Major symptoms include breathlessness and restricted
      activities of daily living due to reduced functional capacity, which in turn
      affects quality of life. Exercise training has been shown to be effective in
      patients with coronary heart disease and has been proposed as an intervention to
      improve exercise tolerance in patients with heart failure. OBJECTIVES: To
      determine the effectiveness of exercise based interventions compared with usual
      medical care on the mortality, morbidity, exercise capacity and health related
      quality of life, of patients with heart failure. SEARCH STRATEGY: We searched the
      Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2001), MEDLINE
      (2000 to March 2001), EMBASE (1998 to March 2001), CINAHL (1984 to March 2001)
      and reference lists of articles. We also sought advice from experts. SELECTION
      CRITERIA: RCTs of exercise based interventions. The comparison group was usual
      medical care as defined by the study, or placebo. Adults of all ages with chronic
      heart failure. Only those studies with criteria for diagnosis of heart failure
      (based on clinical findings or objective indices) have been included. DATA
      COLLECTION AND ANALYSIS: Studies were selected, and data were abstracted,
      independently by two reviewers. Authors were contacted where possible to obtain
      missing information. MAIN RESULTS: Twenty-nine studies met the inclusion
      criteria, with 1126 patients randomised. The majority of studies included both
      patients with primary and secondary heart failure, NYHA class II or III. None of
      the studies specifically examined the effect of exercise training on mortality
      and morbidity as most were of short duration. Exercise training significantly
      increased VO(2) max by (WMD random effects model) 2.16 ml/kg/min (95% CI 2.82 to
      1.49), exercise duration increased by 2.38 minutes (95% CI 2.85 to 1.9), work
      capacity by 15.1 Watts (95% CI 17.7 to 12.6) and distance on the six minute walk
      by 40.9 metres (95% CI 64.7 to 17.1). Improvements in VO(2) max were greater for
      training programmes of greater intensity and duration. HRQoL improved in the
      seven of nine trials that measured this outcome. REVIEWERS' CONCLUSIONS: Exercise
      training improves exercise capacity and quality of life in patients mild to
      moderate heart failure in the short term. There is currently no information
      regarding the effect of exercise training on clinical outcomes. The findings are
      based on small-scale trials in patients who are unrepresentative of the total
      population of patients with heart failure. Other groups (more severe patients,
      the elderly, women) may also benefit. Large-scale pragmatic trials of exercise
      training of longer duration, recruiting a wider spectrum of patients are needed
      to address these issues.

PMID- 15266481
TI  - High first dose quinine regimen for treating severe malaria.
AB  - BACKGROUND: Quinine is used for treating severe malaria. There are arguments for
      giving an initial high dose. We examined the evidence for and against this
      policy. OBJECTIVES: To assess the clinical outcomes and adverse events of a high
      first (loading) dose regimen of quinine compared with a uniform (no loading) dose
      regimen in people with severe malaria. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group's trials register (April 2004), CENTRAL (The Cochrane
      Library Issue 1, 2004), MEDLINE (1966 to April 2004), EMBASE (1974 to April
      2004), LILACS (1982 to April 2004), and conference proceedings for relevant
      abstracts. We also contacted researchers working in the field and checked the
      reference lists of all studies. SELECTION CRITERIA: Randomized controlled trials
      comparing a high first (loading) dose of intravenous quinine with a uniform (no
      loading) dose of intravenous quinine in people with severe malaria. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological
      quality of the trials and extracted data (including adverse event data). We used
      Review Manager 4.2 to analyse the data: relative risk (RR) for binary data and
      weighted mean difference (WMD) for continuous data with 95% confidence intervals
      (CI). We contacted study authors for additional information. MAIN RESULTS: Four
      trials (n = 144) met the inclusion criteria. Loading dose was associated with
      fewer deaths, but this was not statistically significant (RR 0.62, CI 0.19 to
      2.04, 3 trials). Loading dose was associated with faster clearance of parasites
      (WMD -7.44 hours, CI -13.24 to -1.64 hours, 2 trials), resolution of fever (WMD 
      11.11 hours, CI -20.04 to -2.18 hours, 2 trials). No statistically significant
      difference was detected for recovery of consciousness, neurological sequelae, or
      convulsions, but the numbers were small. REVIEWERS' CONCLUSIONS: Quinine loading
      dose reduced fever clearance time and parasite clearance time. Data are
      insufficient to directly demonstrate an impact of loading dose on risk of death.

PMID- 15266482
TI  - Platinum containing regimens for metastatic breast cancer.
AB  - BACKGROUND: Studies have reported high tumour response rates for platinum
      containing regimens in the treatment of women with metastatic breast cancer.
      OBJECTIVES: To identify and review the evidence from randomised trials comparing
      platinum-containing chemotherapy regimens with regimens not containing platinum
      in the management of women with metastatic breast cancer. SEARCH STRATEGY: The
      specialised register maintained by the editorial base of the Cochrane Breast
      Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast
      cancer", "chemotherapy". Details of the search strategy applied to create the
      register, and the procedure used to code references, are described in the
      Cochrane Breast Cancer Group module on The Cochrane Library. SELECTION CRITERIA:
      Randomised trials comparing platinum-containing chemotherapy regimens with
      regimens not containing platinum in women with metastatic breast cancer. DATA
      COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality, and
      data (from published trials) were extracted by two independent reviewers. Hazard
      ratios were derived for time-to-event outcomes, where possible, and a fixed
      effect model was used for meta-analysis. Response rates were analysed as
      dichotomous variables. Toxicity and quality of life data (not available) were
      extracted where present. MAIN RESULTS: Thirteen eligible trials were identified,
      of which 12 had published time-to-event data. The quality of randomisation was
      generally not described.Data, based on an estimated 987 deaths in 1377 women, was
      unable to show a statistically significant difference in favour of platinum
      containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95%
      confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results
      were similar when the analysis was limited to trials in women receiving first
      line chemotherapy. There was no statistically significant difference in favour of
      platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI
      0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p<
      0.0001). There was a statistically significant difference in overall response in
      favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001).
      However, there was strong statistical evidence of heterogeneity (p < 0.00010)
      probably reflecting the varying efficacy of the comparator regimens used in the
      trials. Heterogeneity may also reflect the differences, and difficulties, in
      assessing response. Women receiving platinum-containing regimens experienced
      statistically significant greater toxicity levels for leukopenia, hair loss,
      nausea and vomiting and anaemia compared with those receiving non-platinum
      regimens. REVIEWERS' CONCLUSIONS: In view of the significant excess toxicity,
      lack of progression or survival benefit and the availability of less toxic active
      agents it is difficult to justify the use of platinum-containing regimens,
      particularly as first line treatment for women with metastatic breast cancer in
      routine clinical practice. Ongoing trials are examining the possibility of
      synergy between platins and trastuzamab, a monoclonal antibody treatment. No
      randomised trials containing oxalplatin were identified for the present review.

PMID- 15266483
TI  - Erythropoietin for patients with malignant disease.
AB  - BACKGROUND: Anaemia associated with cancer and cancer therapy is an important
      clinical factor in the treatment of malignant diseases. Therapeutic alternatives
      are recombinant human erythropoietin (EPO) and red blood cell transfusions.
      OBJECTIVES: The aim of this systematic review was to assess the effect of
      erythropoietin to either prevent or treat anaemia in cancer patients. SEARCH
      STRATEGY: We searched the Central Register of Controlled Trials, MEDLINE (01/1985
      to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of
      articles. We also contacted experts in the field and pharmaceutical companies.
      SELECTION CRITERIA: Randomised controlled trials comparing the use of recombinant
      human erythropoietin (plus transfusion if needed) with red blood cell
      transfusions alone for the treatment or prevention of anaemia in cancer patients.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality
      and extracted data. All authors from included studies were contacted for
      additional information. MAIN RESULTS: Twenty seven trials with 3,287 adults were
      included. Use of erythropoietin significantly reduced the relative risk of red
      blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On
      average participants in the erythropoietin group received one unit of blood less
      than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056).
      For participants with baseline haemoglobin below 10 g/dL haematological response
      was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to
      4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves
      tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n =
      1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival
      (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI
      0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant
      adverse effects. Evidence was inconclusive with respect to quality of life and
      fatigue. REVIEWERS' CONCLUSIONS: There is consistent evidence that the
      administration of erythropoietin reduces the risk for blood transfusions and the
      number of units transfused in cancer patients. For patients with baseline
      haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves
      haematological response. There is inconclusive evidence whether erythropoietin
      improves tumour response and overall survival. Research on side effects is
      inconclusive.

PMID- 15266484
TI  - Interventions for treating depression after stroke.
AB  - BACKGROUND: Depressive and anxiety disorders following stroke are often
      undiagnosed or inadequately treated. This may reflect difficulties with the
      diagnosis of abnormal mood among older people with stroke-related disability, but
      may also reflect uncertainty about the effectiveness of such therapies in this
      setting. OBJECTIVES: To determine whether pharmacological, psychological, or
      electroconvulsive treatment (ECT) of depression in patients with stroke can
      improve outcome. SEARCH STRATEGY: The Cochrane Stroke Group Trials Register (last
      searched June 2003). The Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980
      to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September
      2002), Applied Science and Technology Plus (1986 to September 2002), Arts and
      Humanities Index (1991 to September 2002), Biological Abstracts (1969 to
      September 2002), General Science Plus (1994 to September 2002), Science Citation
      Index (1992 to September 2002), Social Sciences Citation Index (1991 to September
      2002), and Sociofile (1974 to September 2002). Reference lists from relevant
      articles and textbooks were searched, and authors of known studies and
      pharmaceutical companies who manufacture psychotropic medications were contacted.
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing
      different types of pharmaceutical agents with placebo, or various forms of
      psychotherapy with standard care (or attention control), in patients with recent,
      clinically diagnosed, acute stroke, where treatment was explicitly intended of
      treat depression. DATA COLLECTION AND ANALYSIS: Primary analyses focussed on the
      prevalence of diagnosable depressive disorder at the end of treatment. Secondary
      outcomes included depression or mood scores on standard scales, disability or
      physical function, death, recurrent stroke, and adverse effects. We did not pool
      the data for summary scores. We performed meta-analysis for only some binary
      endpoints and data on adverse events. MAIN RESULTS: Nine trials, with 780
      participants, were included in the review. Data were available for seven trials
      of pharmaceutical agents, and two trials of psychotherapy. There were no trials
      of ECT. The analyses were complicated by the lack of standardised diagnostic and
      outcome criteria, and differing analytic methods. There was no strong evidence of
      benefit of either pharmacotherapy or psychotherapy in terms of a complete
      remission of depression following stroke. There was evidence of a reduction
      (improvement) in scores on depression rating scales, and an increase in the
      proportion of participants with anxiety at the end of follow up. REVIEWERS'
      CONCLUSIONS: This review found no evidence to support the routine use of
      pharmacotherapeutic or psychotherapeutic treatment for depression after stroke.
      More research is required before recommendations can be made about the most
      appropriate management of depression following stroke.

PMID- 15266485
TI  - Supportive care for patients with gastrointestinal cancer.
AB  - BACKGROUND: Supportive care has traditionally been given to optimise the comfort
      of patients and their ability to function, as well as to minimise the side
      effects of anti-cancer treatments. The scope of modern comprehensive supportive
      care however is broadening and covers not only specific palliative treatment but
      non-tumour specific treatment such as social, psychological and spiritual
      support. In oncology, best supportive care (BSC) has been used as a comparator
      arm of randomised controlled trials in chemotherapy. However the BSC arm is
      usually not well defined and its evaluation is therefore difficult because of the
      heterogeneity of the definitions. A systematic review was undertaken of the
      evidence from all RCTs of gastrointestinal cancers (includes
      gastrointestinal/gastric, colorectal/colon cancer but excludes pancreatic cancer
      trials) which include a BSC/SC arm. OBJECTIVES: 1. To examine the
      effectiveness/outcomes of best supportive care interventions versus cancer
      therapies for gastrointestinal cancer trials;2. To determine whether trials
      containing best supportive care include a definition of this. SEARCH STRATEGY:
      Electronic databases, grey literature sources, citation searching and reference
      checking, handsearches of journals and discussion with experts were used to
      identify potentially eligible trials from both published and unpublished sources.
      SELECTION CRITERIA: RCTs comparing BSC/SC versus anticancer therapies in patients
      with gastrointestinal cancers. DATA COLLECTION AND ANALYSIS: Four RCTs were found
      and reviewed. Because of the heterogeneity of studies, a meta-analysis was not
      attempted. Data was extracted from the included papers and the quality of each
      included study was assessed using the Jadad 1996 and Rinck 1997 methods of
      assessing the quality of RCTs. MAIN RESULTS: Data from four trials (483 patients)
      were included. Due to the heterogeneity of studies (in terms of populations
      studied, the interventions used, the variety of outcomes and assessments used) it
      was not possible to make direct comparisons between the studies. The primary
      outcome in all four trials was survival, in spite of patients with
      advanced/metastatic gastrointestinal cancer having a poor prognosis, and the
      interventions being primarily palliative. REVIEWERS' CONCLUSIONS: Overall the
      results show that for most of the trials included in this review, certain forms
      of chemotherapy plus supportive care improve both survival and quality of life in
      patients with gastrointestinal cancer (gastric and colorectal cancers) compared
      to receiving supportive care alone. Trials involving BSC/SC in patients with
      advanced gastrointestinal cancer require careful evaluation. Oncologists and
      researchers alike should strive for improvements in trial design and reporting.
      Future trials should focus on clearer definitions of supportive care. The EORTC
      definition of supportive care can be used as a guide. BSC/SC trials should use
      standardised validated outcome measures for symptom control, quality of life,
      toxicity and other useful palliative measures.

PMID- 15266486
TI  - Pharmacological and nutritional treatment for McArdle's disease (Glycogen Storage
      Disease type V).
AB  - BACKGROUND: McArdle's disease (Glycogen Storage Disease type V) is caused by the
      absence of the glycolytic enzyme, muscle phosphorylase. Patients present with
      exercise-induced pain, cramps, fatigue, myoglobinuria and acute renal failure,
      which can ensue if the myoglobinuria is severe. OBJECTIVES: To systematically
      review the evidence from randomised controlled trials of pharmacological or
      nutritional treatments in improving exercise performance and quality of life in
      McArdle's disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group register (searched December 2001 and updated in December 2003),
      MEDLINE (January 1966 to December 2003) and EMBASE (January 1980 to December
      2003) using the search term 'McArdle's disease and it's synonym 'Glycogen Storage
      Disease type V'. SELECTION CRITERIA: We included randomised controlled trials
      (including crossover studies) and quasi-randomised trials. Open trials and
      individual patient studies with no patient or observer blinding were included in
      the discussion but not the review. Types of interventions included any
      pharmacological agent or micronutrient or macronutrient supplementation. Primary
      outcome measures included any objective assessment of exercise endurance (for
      example VO2 max, walking speed, muscle force/power and improvement in
      fatiguability). Secondary outcome measures included metabolic changes (such as
      reduced plasma creatine kinase activity and a reduction in the frequency of
      myoglobinuria); subjective measures (including quality of life scores and indices
      of disability); and serious adverse events. DATA COLLECTION AND ANALYSIS: Two
      reviewers checked the titles and abstracts identified by the search,
      independently assessed methodological quality of the full text of potentially
      relevant studies and extracted data onto a specially designed form. MAIN RESULTS:
      We reviewed 20 trials. Ten trials fulfilled the criteria for inclusion and ten
      trials were included in the discussion. The largest treatment trial included 19
      cases, the other trials included fewer than 12 cases. As there were only single
      trials for a given intervention we were unable to undertake a meta-analysis.
      REVIEWERS' CONCLUSIONS: It is not yet possible to recommend any specific
      treatment for McArdle's disease. Low dose creatine supplementation was shown to
      demonstrate a statistically significant benefit, albeit modest, in ischaemic
      exercise in a small number of patients. Ingestion of oral sucrose immediately
      prior to exercise reduces perceived ratings of exertion and heart rate and
      improves exercise tolerance. This treatment will not influence sustained or
      unexpected exercise and may cause significant weight gain. Because of the rarity
      of McArdle's disease, there is a need to develop multicentre collaboration and
      standardised assessment protocols for future treatment trials.

PMID- 15266487
TI  - Botulinum toxin A as an adjunct to treatment in the management of the upper limb
      in children with spastic cerebral palsy.
AB  - BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting
      from a non-progressive lesion in the developing brain. Although the brain lesions
      are static, the movement disorders that arise are not unchanging and are
      characterised by atypical muscle tone, posture and movement (Rang 1990). The
      spastic motor type is the most common form of CP and its conventional therapeutic
      management may include splinting/casting, passive stretching, facilitation of
      posture and movement, spasticity-reducing medication and surgery. More recently,
      health care professionals have begun to use botulinum toxin A (BtA) as an adjunct
      to interventions in an attempt to reduce muscle tone and spasticity to improve
      function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections
      as an adjunct to managing the upper limb in children with spastic CP. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE
      (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004). SELECTION
      CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA
      injections into any muscle group of the upper limb with placebo, no treatment or
      other interventions. DATA COLLECTION AND ANALYSIS: Two authors using standardised
      forms extracted the data independently. Each trial was assessed for internal
      validity with differences resolved by discussion. Data was extracted and entered
      into RevMan 4.2.3. MAIN RESULTS: Two trials met the inclusion criteria, each
      having short-term follow up, a small number of subjects and using a single set of
      injections. The study by Corry 1997 compared BtA with an injection of normal
      saline and found promising results in elbow extension, elbow and wrist muscle
      tone. At three months, encouraging results for wrist muscle tone and grasp and
      release were noted. The trial reported median change, range of changes and the
      difference in these measures between groups. The study by Fehlings 2000 compared
      BtA with no intervention. When data were analysed no treatment effect was found
      for quality of upper limb function, passive range of motion, muscle tone, grip
      strength or self-care ability. REVIEWERS' CONCLUSIONS: This systematic review has
      not found sufficient evidence to support or refute the use of intramuscular
      injections of BtA as an adjunct to managing the upper limb in children with
      spastic cerebral palsy. Only one of the two identified RCTs reported some
      promising results in support of reduced muscle tone following BtA injections.
      Further research incorporating larger sample sizes, rigorous methodology,
      measurement of upper limb function and functional outcomes is essential.

PMID- 15266488
TI  - Pharmacotherapy for patellofemoral pain syndrome.
AB  - BACKGROUND: Patellofemoral pain syndrome (PFPS) is common among adolescents and
      young adults. It is characterised by pain behind or around the patella and
      crepitations, provoked by ascending or descending stairs, squatting, prolonged
      sitting with flexed knees, running and cycling. The symptoms impede function in
      daily activities or sports. Pharmacological treatments focus on reducing pain
      symptoms (non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids),
      or restoring the assumed underlying pathology (compounds containing glucosamine
      to stimulate cartilage metabolism, anabolic steroids to increase bone density of
      the patella and build up supporting muscles). In studies, drugs are usually
      applied in addition to exercises aimed at building up supporting musculature.
      OBJECTIVES: This review aims to summarise the evidence of effectiveness of
      pharmacotherapy in reducing anterior knee pain and improving knee function in
      people with PFPS. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group and Cochrane Rehabilitation and Related Therapies Field trials
      registers, the Cochrane Central Register of Controlled Trials (The Cochrane
      Library Issue 4, 2003), PEDro (up to January 2004), MEDLINE (1966 to January
      2004), EMBASE (1988 to January 2004), and CINAHL (1982 to January 2004).
      SELECTION CRITERIA: Controlled trials (randomised or not) comparing
      pharmacotherapy with placebo, different types of pharmacotherapy, or
      pharmacotherapy to other therapies for people with PFPS. DATA COLLECTION AND
      ANALYSIS: The literature search yielded 780 publications. Eight trials were
      included, of which three were of high quality. Data were analysed qualitatively
      using best evidence synthesis, because meta-analysis was impeded by differences
      in route of administration of drugs, care programs and outcome measures. MAIN
      RESULTS: Four trials (163 participants) studied the effect of NSAIDs. Aspirin
      compared to placebo in a high quality trial produced no significant differences
      in clinical symptoms and signs. Naproxen produced significant short term pain
      reduction when compared to placebo, but not when compared to diflunisal. Laser
      therapy to stimulate blood flow in tender areas led to more satisfied
      participants than tenoxicam, though not significantly. Two high quality RCTs (84
      participants) studied the effect of glycosaminoglycan polysulphate (GAGPS).
      Twelve intramuscular injections in six weeks led to significantly more
      participants with a good overall therapeutic effect after one year, and to
      significantly better pain reduction during one of two activities. Five weekly
      intra-articular injections of GAGPS and lidocaine were compared with intra
      articular injections of saline and lidocaine or no injections, all with
      concurrent quadriceps training. Injected participants showed better function
      after six weeks, though only the difference between GAGPS injected participants
      and non-injected participants was significant. The differences had disappeared
      after one year. One trial (43 participants) found that intramuscular injections
      of the anabolic steroid nandrolone phenylpropionate significantly improved both
      pain and function compared to placebo injections. REVIEWERS' CONCLUSIONS: There
      is only limited evidence for the effectiveness of NSAIDs for short term pain
      reduction in PFPS. The evidence for the effect of glycosaminoglycan polysulphate
      is conflicting and merits further investigation. The anabolic steroid nandrolone
      may be effective, but is too controversial for treatment of PFPS.

PMID- 15266489
TI  - Music therapy for people with dementia.
AB  - BACKGROUND: Dementia is a clinical syndrome with a number of different causes
      which is characterised by deterioration in cognitive functions. Research is
      pursuing a variety of promising findings for the treatment of dementia.
      Pharmacological interventions are available but have limited ability to treat
      many of the syndrome's features. Little research has been directed towards non
      pharmacological treatments. In this review the evidence for music therapy as a
      treatment is examined. OBJECTIVES: To assess the effects of music therapy in the
      treatment of behavioural, social, cognitive and emotional problems of older
      people with dementia. SEARCH STRATEGY: The Cochrane Dementia and Cognitive
      Improvement Group (CDCIG) Specialised Register was searched on 30 June 2003 using
      the term "music*". This Register contains records from all major health care
      databases and many ongoing trial databases and is updated regularly. The
      principal reviewer conducted additional searches to retrieve randomised
      controlled trials (RCTs) concerning the effect of music therapy on older people
      with dementia. SELECTION CRITERIA: Randomised controlled trials that reported
      clinically relevant outcomes associated with music therapy in treatment of
      behavioural, social, cognitive and emotional problems of older people with
      dementia. DATA COLLECTION AND ANALYSIS: Two reviewers screened retrieved studies
      independently for methodological quality using a checklist. Data from accepted
      studies were independently extracted by the reviewers. MAIN RESULTS: Five studies
      were included. The methodological quality of the studies was generally poor and
      the study results could not be validated or pooled for further analyses.
      REVIEWERS' CONCLUSIONS: The methodological quality and the reporting of the
      included studies were too poor to draw any useful conclusions.

PMID- 15266490
TI  - Vaginal chlorhexidine during labour to prevent early-onset neonatal group B
      streptococcal infection.
AB  - BACKGROUND: Early-onset group B beta-hemolytic streptococcus (GBS) infection
      accounts for approximately 30% of neonatal infections, has a high mortality rate
      and is acquired through vertical transmission from colonized mothers. Several
      trials have demonstrated the efficacy of intrapartum chemoprophylaxis (IPC) for
      preventing early-onset disease (EOD). Vaginal disinfection with chlorhexidine
      during labour has been proposed as another strategy for preventing GBS EOD in the
      preterm and term neonate. Chlorhexidine has been found to have no impact on
      antibiotic resistance, is inexpensive, and applicable to poorly equipped delivery
      sites. OBJECTIVES: To determine the effectiveness of vaginal disinfection with
      chlorhexidine during labour for preventing early-onset GBS infection in preterm
      and term neonates. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth trials register (October 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October
      2003), EMBASE (1980 to March 2003), CINAHL (1982 to March 2003) and LILACS (1982
      to September 2003). SELECTION CRITERIA: Randomized and quasi-randomized trials
      comparing vaginal disinfection with chlorhexidine to placebo, or no treatment.
      DATA COLLECTION AND ANALYSIS: We extracted information from the results sections
      of the included studies. We reported relative risk (RR) and risk difference (RD)
      with 95% confidence intervals (CI) for dichotomous outcomes. We calculated the
      number needed to treat (NNT) with 95% CIs when a statistically significant RD was
      found. We used a chi square test (chi2) and the I2 analysis to test for
      heterogeneity, and applied a fixed or random effects model accordingly. MAIN
      RESULTS: Five studies, including approximately 2190 term and preterm infants, met
      the inclusion criteria and reported on at least one of the outcomes of interest
      for this systematic review. When all studies were combined there was a
      statistically significant (p = 0.005) reduction in colonisation (RR 0.72, 95% CI
      0.56 to 0.91); RD -0.16 (95% CI -0.26 to -0.05); NNT 6 (95% CI 4 to 20). There
      was no statistically significant between-study heterogeneity. There was no
      statistically significant between-study heterogeneity both for RR (chi(2) = 3.21
      [p = 0.2], I(2) = 37.8%) and for RD (chi(2) = 1.66 [p = 0.44], I(2) = 0%). There
      was no statistically significant reduction in EOD including GBS infection, GBS
      pneumonia, GBS meningitis or mortality. REVIEWERS' CONCLUSIONS: Vaginal
      chlorhexidine resulted in a statistically significant reduction in GBS
      colonisation of neonates, but was not associated with reductions in other
      outcomes. The review currently does not support the use of vaginal disinfection
      with chlorhexidine in labour for preventing EOD. Results should be interpreted
      with caution as the methodological quality of the studies was poor.

PMID- 15266491
TI  - Anti-IgE for chronic asthma in adults and children.
AB  - BACKGROUND: Omalizumab is a recombinant humanised monoclonal antibody directed
      against immunoglobulin E (IgE) to inhibit the immune system's response to
      allergen exposure. Omalizumab is directed against the binding site of IgE for its
      high affinity Fc receptor. It prevents free serum IgE from attaching to mast
      cells and other effector cells and prevents IgE mediated inflammatory changes.
      OBJECTIVES: To determine the efficacy of anti-IgE in patients with allergic
      asthma SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials
      register (February 2003) for potentially relevant studies. SELECTION CRITERIA:
      Randomised controlled trials examining anti-IgE administered in any manner for
      any duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      study quality and extracted and entered data. Three modes of administration were
      identified from the published literature (inhaled, intravenous and subcutaneous
      injection). Subgroup analysis was performed by asthma severity. Data were
      extracted from published and unpublished sources. MAIN RESULTS: Eight trials were
      included in the review, contributing a total of 2037 mild to severe allergic
      asthmatic participants with high levels of IgE. Treatment with intravenous and
      subcutaneous Omalizumab significantly reduced free IgE compared with placebo.
      Omalizumab led to a significant reduction in inhaled steroid consumption compared
      with placebo: -114 mcg/day (95% CI -150 to -78.13, two trials). There were
      significant increases in the number of participants who were able to reduce
      steroids by over 50%: odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to
      3.10 (four trials); or completely withdraw their daily steroid intake: OR 2.50,
      95%CI 2.00 to 3.13 (four trials). Participants treated with Omalizumab were less
      likely to suffer an asthma exacerbation with treatment as an adjunct to steroids
      (OR 0.49, 95%CI 0.38 to 0.64, four trials), or as a steroid tapering agent (OR
      0.47, 95% CI 0.37 to 0.60, four trials). REVIEWERS' CONCLUSIONS: Omalizumab was
      significantly more effective than placebo at increasing the numbers of patients
      who were able to reduce or withdraw their inhaled steroids, but the mean
      difference in steroid consumption achieved with Omalizumab was of debatable
      clinical value. The impressive effects observed in control groups bring into
      question the true effect of Omalizumab. Omalizumab was effective in reducing
      asthma exacerbations as an adjunctive therapy to inhaled steroids. Omalizumab was
      well tolerated, although the safety profile requires longer term assessment.
      Patient and physician assessment of the drug was positive. Further assessment in
      paediatric and severe adult populations is necessary, as is double-dummy
      comparison with inhaled corticosteroids.

PMID- 15266492
TI  - Chinese herbal medicines for type 2 diabetes mellitus.
AB  - BACKGROUND: Traditional Chinese herbal medicines have been used for a long time
      to treat diabetes, and many controlled trials have been done to investigate their
      efficacy. OBJECTIVES: To assess the effects of Chinese herbal medicines in
      patients with type 2 diabetes mellitus. SEARCH STRATEGY: We searched the
      following electronic databases: The Cochrane Library (CENTRAL), the Chinese
      BioMedical Database, MEDLINE, EMBASE, and LILACS, combined with hand searches on
      Chinese journals and conference proceedings. Date of last search was April 2004.
      No language restriction was used. SELECTION CRITERIA: Randomised trials of herbal
      medicines (with at least two months treatment duration) compared with placebo,
      pharmacological or non-pharmacological interventions were included. DATA
      COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. The
      methodological quality of trials was evaluated using the parameters of
      randomisation, allocation concealment, double blinding, and drop-out rates. Meta
      analyses were performed where data were available. MAIN RESULTS: Sixty-six
      randomised trials, involving 8302 participants, met the inclusion criteria.
      Methodological quality was generally low. Sixty-nine different herbal medicines
      were tested in the included trials, which compared herbal medicines with placebo,
      hypoglycaemic drugs, or herbal medicines plus hypoglycaemic drugs. Compared with
      placebo, Holy basil leaves, Xianzhen Pian, Qidan Tongmai, traditional Chinese
      formulae (TCT), Huoxue Jiangtang Pingzhi, and Inolter showed significantly
      hypoglycaemic response. Compared with hypoglycaemic drugs including
      glibenclamide, tolbutamide, or gliclazide, seven herbal medicines demonstrated a
      significant better metabolic control, including Bushen Jiangtang Tang, Composite
      Trichosanthis, Jiangtang Kang, Ketang Ling, Shenqi Jiangtang Yin, Xiaoke Tang,
      and Yishen Huoxue Tiaogan. In 29 trials that evaluated herbal medicines combined
      with hypoglycaemic drugs, 15 different herbal preparations showed additional
      better effects than hypoglycaemic drugs monotherapy. Two herbal therapies
      combined with diet and behaviour change showed better hypoglycaemic effects than
      diet and behaviour change alone. No serious adverse effects from the herbal
      medicines were reported. REVIEWERS' CONCLUSIONS: Some herbal medicines show
      hypoglycaemic effects in type 2 diabetes. However, these findings should be
      carefully interpreted due to the low methodological quality, small sample size,
      and limited number of trials. In the light of some positive findings, some herbal
      medicines deserve further examination in high-quality trials.

PMID- 15266493
TI  - Face washing promotion for preventing active trachoma.
AB  - BACKGROUND: Trachoma remains a major cause of avoidable blindness among
      underprivileged populations in many developing countries. It is estimated that
      about 146 million people have active trachoma and nearly six million people are
      blind due to complications associated with repeat infections. OBJECTIVES: The
      objective of this review is to assess the effects of face washing on the
      prevalence of active trachoma in endemic communities. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials - CENTRAL (which
      contains the Cochrane Eyes and Vision Group trials register) on The Cochrane
      Library (Issue 2, 2004), MEDLINE (1966 to February 2004), EMBASE (1980 to
      February 2004), the reference lists of identified trials and the Science Citation
      Index. We also contacted investigators and experts in the field to identify
      additional trials. SELECTION CRITERIA: We included randomised or quasi-randomised
      controlled trials, comparing face washing with no treatment or face washing
      combined with antibiotics against antibiotics alone. Participants in the trials
      were people normally resident in endemic trachoma communities. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently extracted data and assessed trial
      quality. Study authors were contacted for additional information. Two clinically
      heterogeneous trials are included, therefore a meta-analysis was considered
      inappropriate. MAIN RESULTS: This review includes two trials with data from a
      total of 2560 participants. Face washing combined with topical tetracycline was
      compared to topical tetracycline alone in three pairs of villages in one trial.
      The trial found a statistically significant effect for face washing combined with
      topical tetracycline in reducing 'severe' active trachoma compared to topical
      tetracycline alone. No statistically significant difference was observed between
      the intervention and control villages in reducing ('non-severe') active trachoma.
      The prevalence of clean faces was higher in the intervention villages than the
      control villages and this was statistically significant. Another trial compared
      eye washing to no treatment or to topical tetracycline alone or to a combination
      of eye washing and tetracycline drops in children with follicular trachoma. The
      trial found no statistically significant benefit of eye washing alone or in
      combination with tetracycline eye drops in reducing follicular trachoma amongst
      children with follicular trachoma. REVIEWERS' CONCLUSIONS: There is some evidence
      that face washing combined with topical tetracycline can be effective in reducing
      severe trachoma and in increasing the prevalence of clean faces. Current evidence
      does not however support a beneficial effect of face washing alone or in
      combination with topical tetracycline in reducing active trachoma.

PMID- 15266494
TI  - Intramuscular penicillin for the prevention of early onset group B streptococcal
      infection in newborn infants.
AB  - BACKGROUND: Early-onset group B streptococcal disease (EOGBSD) is the most
      frequent cause of serious infection in the newborn period. Current strategies
      used to prevent EOGBSD are focused upon maternal antibiotic prophylaxis to reduce
      transmission of GBS to the infant. Observational studies have suggested that the
      administration of intramuscular penicillin to the newborn immediately following
      delivery may be an effective strategy to reduce the incidence of EOGBSD.
      OBJECTIVES: To determine if the administration of intramuscular penicillin to
      newborns at birth is a safe and effective method to prevent morbidity and
      mortality from EOGBSD. SEARCH STRATEGY: The standard search strategy of the
      Neonatal Review Group was used. This included searches of electronic databases:
      Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library Issue 1, 2004), and MEDLINE (1966 - Dec
      2003); and previous reviews including cross references, expert informants and
      journal hand searching in the English language as well as conference and symposia
      proceedings published in Pediatric Research. SELECTION CRITERIA: Randomised
      trials in which intramuscular penicillin was administered as prophylaxis for
      EOGBSD within four hours of birth.Outcomes considered were EOGBSD, neonatal
      mortality, late-onset GBSD, neonatal sepsis, and other secondary outcomes such as
      neurodevelopmental status and length of hospital stay. DATA COLLECTION AND
      ANALYSIS: The search for and assessment of trials for inclusion, quality
      assessment and data extraction were undertaken independently by the reviewers.
      Meta-analysis was not undertaken as data from only one trial is included in this
      review. Data were analysed using relative risk (RR) with 95% confidence intervals
      (CI). MAIN RESULTS: One randomised controlled trial was included in this review.
      In this trial of 1187 infants of birthweight 501 to 2000 grams, there were no
      significant differences found for the outcomes of EOGBSD (RR 0.73; 95%CI 0.32,
      1.62), or neonatal mortality (RR 0.78; 95% CI 0.55, 1.11). No other outcomes were
      able to be assessed. REVIEWERS' CONCLUSIONS: This review does not support the
      routine use of intramuscular penicillin to prevent EOGBSD in newborn infants.
      There is a discrepancy between this finding and the results of a number of larger
      non-randomised trials. Explanations for this are proposed. There is a need for
      this intervention to be tested as a component of the existing prevention
      strategies in widespread use.

PMID- 15266495
TI  - Interventions for treating acute Achilles tendon ruptures.
AB  - BACKGROUND: There is lack of consensus on the best management of the acute
      Achilles tendon (TA) rupture. Treatment can be broadly classified into operative
      (open or percutaneous) and non-operative (cast immobilisation or functional
      bracing). Post-operative splintage can be with a rigid cast (above or below the
      knee) or a more mobile functional brace. OBJECTIVES: To identify and summarise
      the evidence from randomised controlled trials of the effectiveness of different
      interventions in the treatment of acute Achilles tendon ruptures. SEARCH
      STRATEGY: We searched multiple databases including the Cochrane Musculoskeletal
      Injuries Group specialised register (to September 2003), reference lists of
      articles and contacted trialists. Keywords included Achilles Tendon, Rupture, and
      Tendon Injuries. SELECTION CRITERIA: All randomised and quasi-randomised trials
      comparing different treatment regimens for acute Achilles tendon ruptures. DATA
      COLLECTION AND ANALYSIS: Three reviewers extracted data and independently
      assessed trial quality by use of a ten-item scale. MAIN RESULTS: Fourteen trials
      involving 891 patients were included. Several of the studies had poor methodology
      and inadequate reporting of outcomes. Open operative treatment compared with non
      operative treatment (4 trials, 356 patients) was associated with a lower risk of
      rerupture (relative risk (RR) 0.27, 95% confidence interval (CI) 0.11 to 0.64),
      but a higher risk of other complications including infection, adhesions and
      disturbed skin sensibility (RR 10.60, 95%CI 4.82 to 23.28). Percutaneous repair
      compared with open operative repair (2 studies, 94 patients) was associated with
      a shorter operation duration, and lower risk of infection (RR 10.52, 95% CI 1.37
      to 80.52). These figures should be interpreted with caution because of the small
      numbers involved. Patients splinted with a functional brace rather than a cast
      post-operatively (5 studies, 273 patients) tended to have a shorter in-patient
      stay, less time off work and a quicker return to sporting activities. There was
      also a lower complication rate (excluding rerupture) in the functional brace
      group (RR 1.88 95%CI 1.27 to 2.76). Because of the small number of patients
      involved no definitive conclusions could be made regarding different operative
      techniques (1 study, 51 patients), different non-operative treatment regimes (2
      studies, 90 patients), and different forms of post-operative cast immobilisation
      (1 study, 40 patients). REVIEWERS' CONCLUSIONS: Open operative treatment of acute
      Achilles tendon ruptures significantly reduces the risk of rerupture compared to
      non-operative treatment, but produces a significantly higher risk of other
      complications, including wound infection. The latter may be reduced by performing
      surgery percutaneously. Post-operative splintage in a functional brace appears to
      reduce hospital stay, time off work and sports, and may lower the overall
      complication rate.

PMID- 15266496
TI  - Pre and post operative medical therapy for endometriosis surgery.
AB  - BACKGROUND: Endometriosis is a common gynaecological condition which affects
      approximately 10% of women of reproductive age (Askenazi 1997). There is a range
      of symptoms and most commonly women present with dysmenorrhoea, pelvic pain,
      infertility or a pelvic mass. Direct visualisation and biopsy during laparoscopy
      or laparotomy is the gold standard diagnostic test for this condition and enables
      the gynaecologist to identify the location, extent and severity of the disease.
      Surgical therapy can be performed concurrently with diagnostic surgery and may
      include removal (excision) or destruction (ablation) of endometriotic tissue,
      division of adhesions and removal of endometriotic cysts. Laparoscopic excision
      or ablation of endometriosis has been shown to be effective in the management of
      pain in mild-moderate endometriosis. Adjunctive medical treatment pre or post
      operatively may prolong the symptom-free interval. OBJECTIVES: To determine the
      effectiveness of systemic medical therapies used for hormonal suppression before
      or after surgery for endometriosis, or before and after surgery for endometriosis
      in the eradication of endometriosis, improvement of symptoms, pregnancy rates and
      overall tolerability by comparing them with no treatment or placebo. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility group
      trials register (searched 10 September 2003), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2003), MEDLINE (January
      1966 to September 2003), EMBASE (January 1985 to September 2003) and reference
      lists of articles. We also contacted researchers in the field. SELECTION
      CRITERIA: Trials were included if they were randomised controlled trials of the
      use of systemic medical therapies for hormonal suppression before or after, or
      before and after surgery for endometriosis. DATA COLLECTION AND ANALYSIS: Data
      extraction and quality assessment was performed independently by using relative
      risk or weighted mean difference and 95% confidence intervals. MAIN RESULTS:
      Eleven trials were included in the review. One study comparing pre-surgical
      medical therapy with surgery alone showed a significant improvement in AFS scores
      in the medical therapy group (WMD -9.60, 95% CI -11.42 to -7.78) but this may or
      may not be associated with better outcomes for the patients. Post surgical
      hormonal suppression of endometriosis compared to surgery alone (either no
      medical therapy or placebo) showed no benefit for the outcomes of pain or
      pregnancy rates but a significant improvement in disease recurrence (AFS scores
      (WMD -2.30, 95% CI -4.02 to -0.58)). There were no trials identified in the
      search that compared hormonal suppression of endometriosis before and after
      surgery with surgery alone. There is no significant difference between pre
      surgery hormonal suppression and post surgery hormonal suppression for the
      outcome of pain in the one trial identified (RR 1.01, 95% CI 0.49 to 2.07).
      Information concerning AFS scores and ease of surgery was reported only as a
      descriptive summary so any difference between the groups can not be quantified
      from the information in the report of this trial. REVIEWERS' CONCLUSIONS: There
      is insufficient evidence from the studies identified to conclude that hormonal
      suppression in association with surgery for endometriosis is associated with a
      significant benefit with regard to any of the outcomes identified. There may be a
      benefit of improvement in AFS scores with the pre-surgical use of medical
      therapy. The possible benefit should be weighed in the context of the adverse
      effects and costs of these therapies.

PMID- 15266497
TI  - Vasopressors for shock.
AB  - BACKGROUND: Besides reversing the underlying cause, the first line treatment for
      the symptoms of shock is usually the administration of intravenous fluids. If
      this method is not successful, vasopressors such as dopamine, dobutamine,
      adrenaline, noradrenaline and vasopressin are recommended. It is unclear if there
      is a vasopressor of choice, either for the treatment of particular forms of shock
      or for the treatment of shock in general. OBJECTIVES: To assess the efficacy of
      vasopressors for circulatory shock in critically ill patients. Our main aim was
      to assess whether particular vasopressors reduce overall mortality. We also
      intended to identify whether the choice of vasopressor influences outcomes such
      as length-of-stay in the intensive care unit and health-related quality of life.
      SEARCH STRATEGY: We searched MEDLINE, the Cochrane Central Register of Controlled
      Trials, EMBASE, PASCAL BioMed, CINAHL, BIOSIS, and PsychINFO:all from inception
      to November 2003; for randomized controlled trials. We also asked experts in the
      field and searched meta-registries for ongoing trials. SELECTION CRITERIA: We
      included randomized controlled trials comparing various vasopressors,
      vasopressors with placebo or vasopressors with intravenous fluids for the
      treatment of any kind of circulatory failure (shock). Mortality was the main
      outcome. DATA COLLECTION AND ANALYSIS: Two reviewers abstracted data
      independently. Disagreement between two reviewers was discussed and resolved with
      a third reviewer. We used random effects models for combining quantitative data.
      MAIN RESULTS: We identified eight randomized controlled trials. Reporting of
      methodological details was for many items not satisfactory: only two studies
      reported allocation concealment, and two that the outcome assessor was blind to
      the intervention. Two studies compared norepinephrine plus dobutamine with
      epinephrine alone in patients with septic shock (52 patients, relative risk of
      death 0.98, 95% confidence interval 0.57 to 1.67). Three studies compared
      norepinephrine with dopamine in patients with septic shock (62 patients, relative
      risk 0.88, 0.57 to 1.36). Two studies compared vasopressin with placebo in
      patients with septic shock (58 patients, relative risk 1.04, 0.06 to 19.33). One
      study compared terlipressin with norepinephrine in patients with refractory
      hypotension after general anaesthesia but there were no deaths (20 patients).
      REVIEWERS' CONCLUSIONS: The current available evidence is not suited to inform
      clinical practice. We were unable to determine whether a particular vasopressor
      is superior to other agents in the treatment of states of shock.

PMID- 15266498
TI  - Herbal medicines for viral myocarditis.
AB  - BACKGROUND: Herbal medicines are being used for treating viral diseases including
      viral myocarditis, and many controlled trials have been done to investigate their
      efficacy. OBJECTIVES: To assess the effects of herbal medicines on clinical and
      indirect outcomes in patients with viral myocarditis. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The
      Cochrane Library 2003, Issue 3, MEDLINE (January 1966 to October 2003), EMBASE
      (January 1998 to October 2003), Chinese Biomedical Database (1979-2003), AMED
      (1985-2003), LILACS accessed in October 2003 and the trials register of the
      Cochrane Complementary Medicine Field. We handsearched Chinese journals and
      conference proceedings. No language or publication restrictions were used.
      SELECTION CRITERIA: Randomised controlled trials of herbal medicines (with a
      minimum of seven days treatment duration) compared with placebo, no intervention,
      or conventional interventions were included. Trials of herbal medicine plus
      conventional drug versus drug alone were also included. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently extracted data and evaluated trial quality.
      Study authors were contacted for additional information. Adverse effects
      information was collected from the trials. MAIN RESULTS: Forty randomised trials,
      involving 3448 people were included. All trials were conducted and published in
      China, and the methodological quality was assessed as generally low. No trial had
      diagnosis of viral myocarditis confirmed histologically, and few trials attempted
      to establish viral aetiology for the myocarditis. Twenty-five different herbal
      medicines were tested in the included trials, which compared herbs with
      supportive therapy (17 trials), other controls (three trials), or treatment of
      herbs plus supportive therapy with supportive therapy alone (20 trials). The
      trials reported electrocardiogram, myocardial enzymes, cardiac function,
      symptoms, and adverse effects. Astragalus membranaceus (either as single herb or
      compound of herbs) showed significantly effects on improving arrhythmia, CPK
      levels, and cardiac function. Salviae miltiorrhizae injection showed significant
      effects on decreasing the arrhythmia and reducing LDH levels. Shenmai and
      Shengmai injection (Ginseng preparation) showed significantly effects on reducing
      myocardial enzymes and improving cardiac function. No serious adverse effect was
      reported. REVIEWERS' CONCLUSIONS: Some herbal medicines may have anti-arrhythmia
      effect in suspected viral myocarditis. However, interpretation of these findings
      should be careful due to the low methodological quality, small sample size, and
      limited number of trials on individual herbs. In the light of the findings, some
      herbal medicines deserve further examination in rigorous trials.

PMID- 15266499
TI  - Soy formula for prevention of allergy and food intolerance in infants.
AB  - BACKGROUND: Allergies and food reactions in infants and children are common and
      may be associated with foods including adapted cow's milk formulas. Soy based
      formulas have been used to treat infants with allergy or food intolerance.
      However, it is unclear whether they can be advocated for the prevention of
      allergy and food intolerance in infants without clinical evidence of allergy or
      food intolerance. OBJECTIVES: In infants without clinical evidence of allergy or
      food intolerance, to determine whether feeding them an adapted soy formula
      compared to human milk, cow's milk formula or a hydrolysed protein formula
      prevents allergy or food intolerance. SEARCH STRATEGY: The standard search
      strategy of the Cochrane Neonatal Review Group was used including searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 4, 2003), MEDLINE (1966 - January 2004), EMBASE (1980 - January 2004),
      CINAHL (1982 - December 2003) and previous reviews including cross references.
      SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use
      of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed
      protein formula for infant feeding in the first 6 months. Only trials with > 80%
      follow up of participants and reported in group of assignment were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion,
      methodological quality and data extraction were assessed independently by each
      reviewer. Primary outcomes included clinical allergy, specific allergies and food
      intolerance. Meta-analysis was conducted using a fixed effects model where no
      heterogeneity of treatment effect existed, and a random effects model when
      heterogeneity was found. MAIN RESULTS: Five eligible studies were found, all
      enrolling infants at high risk of allergy on the basis of a family history of
      allergy in a first degree relative. All studies compared use of a soy to a cow's
      milk formula. Two studies also included a group fed a formula containing
      hydrolysed protein. No eligible study enrolled infants fed human milk. No study
      examined the effect of early, short term soy formula feeding. Three studies were
      of good methodology and did not have unbalanced allergy-preventing co
      interventions in the treatment groups. Comparing soy to cow's milk formula, one
      study with unclear allocation concealment and 19.5% losses to follow up reported
      a reduction in cumulative incidence of childhood allergy, asthma and allergic
      rhinitis. No other study reported a significant benefit for any allergy or food
      intolerance. Analysis found no significant difference in allergy cumulative
      incidence in infancy (one study: RR 1.02, 95% CI 0.69, 1.49) or childhood (3
      studies: typical RR 0.73, 95% CI 0.37, 1.44) and no significant difference in
      cumulative incidence or period prevalence of any specific allergy or food
      intolerance in infancy or childhood. Analysis of studies comparing soy to a
      hydrolysed formula found a significant increase in infant (one study: RR 1.67,
      95% CI 1.03, 2.69) and childhood allergy cumulative incidence (one study: RR
      1.55, 95% CI 1.02, 2.35), infant eczema cumulative incidence (2 studies: typical
      RR 2.34, 95% CI 1.51, 3.62) and childhood food allergy period prevalence (one
      study: RR 1.81, 95% CI 1.09, 3.02). REVIEWERS' CONCLUSIONS: Feeding with a soy
      formula should not be recommended for the prevention of allergy or food
      intolerance in infants at high risk of allergy or food intolerance.

PMID- 15266500
TI  - Hepatitis B vaccination for patients with chronic renal failure.
AB  - BACKGROUND: Chronic renal failure patients are at particular risk of hepatitis B
      virus infection. Early studies have demonstrated that renal failure patients
      benefit from vaccination; however, not all studies have consistently shown
      benefit. OBJECTIVES: To determine the beneficial and harmful effects of hepatitis
      B vaccine and of a reinforced vaccination series in chronic renal failure
      patients. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register, The Cochrane Renal Group Controlled Trials Register,
      The Cochrane Controlled Trials Register on The Cochrane Library (Issue 1,
      2002),PubMed/MEDLINE (1966 to July 2003), EMBASE (1985 to November 2003), Current
      Clinical Practice Guidelines (Canadian Immunization Guide and Vaccine Preventable
      Diseases Surveillance Manual), and Science Citation Index as well as journals,
      published abstracts, and reference lists of articles. SELECTION CRITERIA:
      Randomised clinical trials comparing plasma vaccine with placebo, recombinant
      vaccine with placebo, recombinant vaccine with plasma vaccine, and a reinforced
      vaccination series (ie, more than three inoculations) with three inoculations of
      vaccine in chronic renal failure patients. DATA COLLECTION AND ANALYSIS: Primary
      outcome measures included incidence of patients developing hepatitis B virus
      antibodies and infections while secondary outcomes included adverse events, liver
      related morbidity, and mortality. Random effects models were used and reported
      relative risks and 95% confidence intervals (RR and 95% CI). MAIN RESULTS: We
      included seven randomised clinical trials. None of them had high quality. Plasma
      vaccine was significantly more effective than placebo in achieving hepatitis B
      antibodies (RR 23.0, 95% CI 14.39 to 36.76, 3 trials). We found no statistically
      significant difference between plasma vaccine or placebo regarding hepatitis B
      virus infections (RR 0.50, 95% CI 0.20 to 1.24). We found no statistically
      significant differences between recombinant vaccine and plasma vaccine in
      achieving hepatitis B antibodies (RR 0.65, 95% CI 0.28 to 1.53, 2 trials).
      Heterogeneity was significant and appeared to be attributable to the dose of
      vaccine. Two trials examined a reinforced recombinant vaccine strategy, which was
      not statistically more effective than three inoculations of recombinant vaccine
      regarding development of hepatitis B antibodies (RR 1.36, 95% CI 0.85 to 2.16).
      REVIEWERS' CONCLUSIONS: Plasma derived vaccines are more effective than placebo
      in achieving hepatitis B antibodies, while no statistically significant
      difference was found between recombinant and plasma vaccines. No statistically
      significant difference of effectiveness was observed between a reinforced
      vaccination series versus routine vaccinations of three inoculations of
      recombinant vaccine.

PMID- 15266501
TI  - Spinal cord stimulation for chronic pain.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is a form of therapy used to treat
      certain types of chronic pain. It involves an electrical generator that delivers
      pulses to a targeted spinal cord area. The leads can be implanted by laminectomy
      or percutaneously and the source of power is supplied by an implanted battery or
      by an external radio-frequency transmitter. The exact mechanism of action of SCS
      is poorly understood. OBJECTIVES: To assess the efficacy and effectiveness of
      spinal cord stimulation in relieving certain kinds of pain, as well as the
      complications and adverse effects of this procedure. SEARCH STRATEGY: We searched
      MEDLINE and EMBASE to September 2003; the Cochrane Central Register of Controlled
      Trials (CENTRAL) (Issue 3, 2003); textbooks and reference lists in retrieved
      articles. We also contacted experts in the field of pain and the main
      manufacturer of the stimulators. SELECTION CRITERIA: We included trials with a
      control group, either randomized controlled trials (RCTs) or non-randomized
      controlled clinical trials (CCTs), that assessed spinal cord stimulation for
      chronic pain. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected
      the studies, assessed study quality and extracted the data. One of the assessors
      of methodological quality was blinded to authors, dates and journals. The data
      were analysed using qualitative methods (best evidence synthesis). MAIN RESULTS:
      Two RCTs (81 patients in total) met our inclusion criteria. One was judged as
      being of high quality (score of 3 on Jadad scale) and the other of low quality
      (score of 1 on Jadad scale). One trial included patients with Complex Regional
      Pain Syndrome Type I (reflex sympathetic dystrophy) and the other patients with
      Failed Back Surgery Syndrome. The follow-up periods varied from 6 to 12 months.
      Both studies reported that SCS was effective, however, meta-analysis was not
      undertaken because of the small number of patients and the heterogeneity of the
      study population. REVIEWERS' CONCLUSIONS: Although there is limited evidence in
      favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain Syndrome
      Type I, more trials are needed to confirm whether SCS is an effective treatment
      for certain types of chronic pain. In addition, there needs to be a debate about
      trial designs that will provide the best evidence for assessing this type of
      intervention.

PMID- 15266502
TI  - Combined corticosteroid and long acting beta-agonist in one inhaler for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have both been
      recommended in guidelines for the treatment of chronic obstructive pulmonary
      disease. Their co-administration in a combined inhaler is intended to facilitate
      adherence to medication regimens, and to improve efficacy. OBJECTIVES: To assess
      the efficacy of combined inhaled corticosteroid and long-acting beta-agonist
      preparations, compared to placebo or the individual components, in the treatment
      of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We
      searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD)
      trials register. Date of last search April 2004. SELECTION CRITERIA: Studies were
      included if they were randomised and double-blind. Studies could compare a
      combined inhaled corticosteroids and long-acting beta-agonist preparation with
      either component preparation or placebo. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and extracted data. The primary
      outcome was exacerbations. MAIN RESULTS: Six randomised trials with 4118
      participants were included. Two different combination preparations
      (fluticasone/salmeterol and budesonide/formoterol) were used. Combination
      treatment was more effective than placebo for mean exacerbation rates, quality of
      life and lung function. No trials were found comparing the combination of drugs
      in a single inhaler with the same drugs both given in separate inhalers.
      Exacerbations: Fluticasone/salmeterol did not significantly reduce exacerbations
      compared with either of its component treatments in one large study. There was no
      significant difference when budesonide/formoterol was compared with budesonide.
      Budesonide/formoterol was more effective than formoterol in reducing
      exacerbations (Rate ratio: 0.78 [0.68 to 0.90], two studies). A pooled analysis
      of both combination therapies indicated that exacerbations were less frequent
      when compared with either placebo or long-acting beta-agonist (versus placebo
      Rate ratio: 0.76 [0.68, 0.84], three studies, versus beta-agonist, Rate ratio:
      0.85 [0.77, 0.95], three studies), but not when compared with steroid. The
      clinical impact of this effect depends on the frequency of exacerbations
      experienced by patients. One full exacerbation was prevented for every two to
      four years of treatment in the type of patients included in the trials. Quality
      of Life: There were conflicting findings in quality of life and symptoms when
      fluticasone/salmeterol was compared with inhaled steroids alone (three studies).
      There was no significant difference between fluticasone/salmeterol and long
      acting beta-agonist in quality of life scores (three studies).
      Budesonide/formoterol improved symptoms when compared with budesonide but not
      with formoterol. There were conflicting findings in quality of life scores when
      budesonide/formoterol was compared with component inhaled corticosteroid or beta
      agonist. These may be accounted for by different study design. Lung Function:
      Treatment with either combination led to small, significant differences in lung
      function compared with component steroid medication. Fluticasone/salmeterol led
      to small improvements in FEV1 compared with salmeterol, but budesonide/formoterol
      treatment did not increase FEV1 significantly when compared with formoterol.
      REVIEWERS' CONCLUSIONS: Compared with placebo, combination therapy led to
      clinically meaningful differences in quality of life, symptoms and exacerbations.
      However, there were conflicting results when the different combination therapies
      were compared with the mono-components alone. In order to draw firmer conclusions
      about the effects of combination therapy in a single inhaler more data are
      necessary, including the assessment of the comparative effects with separate
      administration of the two drugs in double-dummy trials.

PMID- 15266503
TI  - Fluorides for the prevention of white spots on teeth during fixed brace
      treatment.
AB  - BACKGROUND: White spots can appear on teeth during fixed brace treatment because
      of early decay around the brace attachments. Fluoride is effective at reducing
      decay in susceptible individuals and is routinely prescribed in various different
      forms to patients during orthodontic treatment. OBJECTIVES: To evaluate the
      effectiveness of fluoride in preventing white spots during orthodontic treatment
      and to compare the different modes of delivery of fluoride. SEARCH STRATEGY: We
      searched the Cochrane Oral Health Group's Trials Register (to 22 August 2002);
      CENTRAL (The Cochrane Library Issue 3, 2002); MEDLINE (January 1966 to July
      2003); EMBASE (January 1980 to week July 2003). Authors of trials were contacted
      for further data. SELECTION CRITERIA: Trials were selected if they met the
      following criteria: a randomised or quasi-randomised clinical trial, involving
      the use of a fluoride-containing product compared with no use or use of a non
      fluoride control and enamel demineralisation was assessed during or after
      orthodontic treatment. DATA COLLECTION AND ANALYSIS: Six reviewers independently,
      in duplicate, extracted data. The primary outcome was the difference in the
      presence or absence of white spots between experimental and control patients for
      parallel design studies, and between experimental and control quadrants, for
      split-mouth design studies. Potential sources of heterogeneity were examined.
      Sensitivity analyses were undertaken for the items assessed for quality and
      publication bias. MAIN RESULTS: The primary outcome of the review was the
      presence or absence of white spots by patient at the end of treatment. Secondary
      outcomes included any quantitative assessment of enamel mineral loss or lesion
      depth. Other outcomes such as differences in size and severity of white spots,
      any patient based outcomes, such as perception of white spots could not be
      included because there were insufficient data. Fifteen trials, with 723
      participants, provided data for this review. None of the studies fulfilled all of
      the methodological quality assessment criteria. There is some evidence that a
      daily sodium fluoride mouthrinse reduces the severity of enamel decay surrounding
      a fixed brace (weighted mean difference for lesion depth -70.0; 95% CI -118.2 to 
      21.8) and that use of a glass ionomer cement for bracket bonding reduces the
      prevalence (Peto OR 0.35; 95% CI 0.15 to 0.84) and severity of white spots
      (weighted mean difference for mineral loss -645 vol%.microm; 95% CI -915 to -375)
      compared with composite resins. REVIEWERS' CONCLUSIONS: There is some evidence
      that the use of topical fluoride or fluoride-containing bonding materials during
      orthodontic treatment reduces the occurrence and severity of white spot lesions,
      however there is little evidence as to which method or combination of methods to
      deliver the fluoride is the most effective. Based on current best practice in
      other areas of dentistry, for which there is evidence, we recommend that patients
      with fixed braces rinse daily with a 0.05% sodium fluoride mouthrinse. More high
      quality, clinical research is required into the different modes of delivering
      fluoride to the orthodontic patient.

PMID- 15266504
TI  - Omega-3 fatty acids for intermittent claudication.
AB  - BACKGROUND: Omega-3 fatty acids are established as being effective in the
      treatment and prevention of coronary artery disease. It is possible that they may
      also benefit people with peripheral arterial disease, since the pathogenesis of
      the two conditions is similar. OBJECTIVES: To determine the effects of omega-3
      supplementation in people with intermittent claudication. SEARCH STRATEGY: Trials
      were identified from the Cochrane Peripheral Vascular Diseases Group trials
      register (last searched April 2004), and the Cochrane Central Register of
      Controlled Trials (CENTRAL) (last searched Issue 1, 2004). In addition,
      literature from pharmaceutical companies (Roche Pharmaceuticals and Seven Seas),
      manufacturers of omega-3 rich foods (Columbus Eggs) and web sites of nutritional
      organisations dedicated to omega-3 fatty acids (Omega-3 information and the Fish
      Foundation) were searched. SELECTION CRITERIA: Randomised controlled trials of
      omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with
      intermittent claudication. DATA COLLECTION AND ANALYSIS: One reviewer (TS)
      identified potential trials, assessed study quality and extracted data. The other
      reviewer (WH) assessed study quality and checked data extraction. MAIN RESULTS:
      Four studies were included involving a total of 203 participants. The overall
      methodological quality of studies was good. All studies compared omega-3 fatty
      acid supplementation with placebo. Two studies used an omega-6 fatty acid as the
      placebo preparation, one used a monounsaturated fatty acid and one used a
      combination of omega-6 and monounsaturated fatty acids.Omega-3 fatty acid
      supplementation reduced triglyceride levels (weighted mean difference (WMD) -0.66
      mmol/litre; 95% confidence interval (CI) -1.24 to -0.09) and diastolic blood
      pressure (WMD -1.94 mmHg; 95% CI -3.58 to -0.29) in the treatment group, but
      increased total cholesterol levels (WMD 0.41 mmol/litre; 95% CI 0.03 to 0.80) and
      LDL cholesterol levels (WMD 0.43 mmol/litre; 95% CI 0.12 to 0.74).
      Gastrointestinal side-effects were observed in one study. No significant changes
      were observed in pain-free walking distance (WMD -17 m; 95% CI -51 to 17 m),
      maximal walking distance (WMD -21 m; 95% CI -59 to 17 m) or ankle brachial
      pressure index (WMD -0.03; 95% CI -0.1 to 0.04). REVIEWERS' CONCLUSIONS: Omega-3
      fatty acids appear to have some beneficial biochemical and haemodynamic effects
      in people with intermittent claudication but there is no evidence of improved
      clinical outcomes. It should be noted that no consistent effect on primary
      outcome measures was detected. Further research is needed in this area, to
      evaluate short- and long-term effects on more clinically relevant outcomes.

PMID- 15266505
TI  - Interventions for replacing missing teeth: different times for loading dental
      implants.
AB  - BACKGROUND: To minimize the risk of implant failure, osseointegrated oral
      implants are conventionally kept load-free during the healing period. During
      healing removable prostheses are used, however many patients find these temporary
      prostheses rather uncomfortable and it would be beneficial if the healing period
      could be shortened without jeopardizing implant success. Nowadays immediate and
      early loaded implants are commonly used in mandibles of good bone quality. It
      would be useful to know whether there is a difference in success rates between
      immediately or early loaded implants compared with conventionally loaded
      implants. OBJECTIVES: To test the null hypothesis of no difference in the
      clinical performance between osseointegrated implants loaded at different times 1
      year after loading. SEARCH STRATEGY: The Cochrane Oral Health Group's Trials
      Register, The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE
      were searched. Handsearching included several dental journals. Authors of all
      identified trials, an internet discussion group and 55 oral implant manufacturers
      were contacted to find unpublished randomized controlled trials (RCTs). The last
      electronic search was conducted on 2 February 2004. SELECTION CRITERIA: All RCTs
      of root-form osseointegrated oral implants having a follow up of at least 1 year
      comparing the same osseointegrated root-form oral implants loaded at different
      times. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in
      duplicate, by two reviewers. Authors were contacted for details of randomization
      and withdrawals and a quality assessment was carried out. The Cochrane Oral
      Health Group's statistical guidelines were followed. MAIN RESULTS: Seven RCTs
      were identified and five trials including 124 patients in total were suitable for
      inclusion. Implants have been either immediately loaded after insertion (2 to 3
      days), early loaded (6 weeks) or conventionally loaded (3 to 8 months) in
      edentulous mandibles of adequate bone quality and shape. On a patient, rather
      than per implant basis, there were no statistically significant differences for
      prosthesis failures, implant failures and marginal bone loss on intra-oral
      radiographs. REVIEWERS' CONCLUSIONS: While it is possible to successfully load
      oral implants immediately after their placement in mandibles of adequate bone
      density and height of carefully selected patients, it is yet unknown how
      predictable this approach is. More well designed RCTs are needed to understand
      how predictable immediate and early loading are. Such trials should be simply
      designed and should be reported according to the CONSORT guidelines
      (http://www.consort-statement.org/). It is suggested that priority should be
      given to trials assessing the effectiveness of immediately loaded implants rather
      than early loaded ones.

PMID- 15266506
TI  - Inhaled insulin in diabetes mellitus.
AB  - BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin.
      However this is a considerable burden to many people with diabetes and adherence
      to such an insulin regimen can be difficult to maintain, hence compromising
      optimal glycaemic control. Also, short acting injected insulin is absorbed more
      slowly than insulin released by the normal pancreas in response to a meal.
      Inhaled insulin has the potential to reduce the number of injections to perhaps
      one long-acting insulin per day, and provide a closer match to the natural state,
      by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy,
      adverse effects and patient acceptability of inhaled versus injected insulin.
      SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross
      over trials was combined with key terms for inhaled insulins. Databases searched
      were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index,
      BIOSIS, Web of Science Proceedings, National Research Register UK, Current
      Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and
      web sites of the ADA and EASD were searched for recent meeting abstracts.
      Reference lists and journals were handsearched. There were no language
      restrictions on searching. Manufacturers of inhaled insulin were also contacted.
      Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled
      trials with parallel groups or controlled cross-over trials, including type 1 or
      type 2 diabetic patients of any age treated with insulin, were considered
      eligible. The minimum trial duration considered was 10 weeks, as this is the time
      taken for glycated haemoglobin to reliably reflect changes in glycaemic control.
      DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was
      performed independently by two reviewers. The quality of reporting of each trial
      was assessed according to a modification of the criteria outlined in Centre for
      Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six
      randomised controlled trials were found and the overall number of participants
      was 1191. Three trials included patients with type 1 diabetes and three with type
      2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All
      were open label. There was insufficient information to determine the study
      quality. Results for HbA1c were similar for all trials, in that all showed
      comparable glycaemic control for inhaled insulin compared to an entirely
      subcutaneous regimen. All trials that reported patient satisfaction and quality
      of life showed that these were significantly greater in the inhaled insulin
      group. Overall there was no difference in total hypoglycaemic episodes between
      the groups, but one trial showed a statistically significant increase in severe
      hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary
      effects were observed in any of the studies, but longer follow-up will be
      required to be sure that there are no adverse side-effects. Cavets include: few
      studies published in full (so quality could not be assessed), and only two
      studies used the same basal regimen in both the inhaled and injected groups.
      REVIEWERS' CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with
      an injected basal insulin, has been shown to maintain glycaemic control
      comparable to that of patients taking multiple daily injections. The key benefit
      appears to be that patient satisfaction and quality of life are significantly
      improved, presumably due to the reduced number of daily injections required.
      However, the patient satisfaction data is based on five trials, of which only two
      have been published in full; also the three trials containing quality of life
      data are all only published in abstract form at present. In addition, longer term
      pulmonary safety data are still needed. Also, the lower bioavailability, and
      hence higher doses of inhaled insulin required, may make it less cost-effective
      than injected insulin.

PMID- 15266507
TI  - Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is an
      uncommon progressive or relapsing paralysing disease caused by inflammation of
      the peripheral nerves. If the hypothesis that it is due to autoimmunity is
      correct, removal of autoantibodies in the blood by plasma exchange should be
      beneficial. OBJECTIVES: To evaluate the efficacy of plasma exchange in chronic
      inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We searched
      the Neuromuscular Disease Group Register (December 2003), and MEDLINE (January
      1966 to January 2003), EMBASE (January 1980 to January 2003), CINAHL (January
      1982 to December 2002) and LILACS (January 1982 to January 2003). We also
      scrutinised the bibliographies of the trials, and contacted the trial authors and
      other disease experts. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials in participants of any age comparing plasma exchange with sham
      treatment or no treatment. A trial showing no significant difference in the
      benefit from plasma exchange with intravenous immunoglobulin has been included in
      a separate Cochrane review. DATA COLLECTION AND ANALYSIS: Two authors selected
      the trials, extracted the data and assessed methodological quality independently.
      Where possible data were combined according to the methods of the Cochrane
      Neuromuscular Disease Review Group. MAIN RESULTS:  PRIMARY OUTCOME MEASURE: one
      crossover trial including 18 participants showed 2 (95% confidence interval (CI)
      0.8 to 3.0) points more improvement after four weeks in an 11-point disability
      scale with plasma exchange (10 exchanges over four weeks) than with sham
      exchange. Rapid deterioration after plasma exchange occurred in eight of 12 who
      had improved. SECONDARY OUTCOME MEASURES: when the results of this trial and
      another with 29 participants treated in a parallel group design trial were
      combined, there were 31 points (95% CI 16 to 45) more improvement in an
      impairment scale after plasma exchange (six exchanges over three weeks) than
      after sham exchange. There were significant improvements in both trials in an
      electrophysiological measure, the proximally evoked compound muscle action
      potential, after three or four weeks. Non-randomised evidence indicates that
      plasma exchange induces adverse events in 3% to 17% of procedures. These are
      sometimes serious. REVIEWERS' CONCLUSIONS: Evidence from two small trials showed
      that plasma exchange provides significant short-term benefit in about two-thirds
      of patients with chronic inflammatory demyelinating polyradiculoneuropathy but
      rapid deterioration may occur afterwards. Adverse events related to difficulty
      with venous access, use of citrate and haemodynamic changes are not uncommon.
      More research is needed to identify agents which will prolong the beneficial
      action of plasma exchange.

PMID- 15266508
TI  - Preoperative skin antiseptics for preventing surgical wound infections after
      clean surgery.
AB  - BACKGROUND: Approximately 15% of elective surgery patients and 30% of patients
      receiving contaminated or dirty surgery are estimated to develop post-operative
      wound infections. The costs of surgical wound infection can be considerable in
      financial as well as social terms. Preoperative skin antisepsis is performed to
      reduce the risk of post-operative wound infections by removing soil and transient
      organisms from the skin. Antiseptics are thought to be both toxic to bacteria and
      aid their mechanical removal. The effectiveness of preoperative skin preparation
      is thought to be dependent on both the antiseptic used and the method of
      application, however it is unclear whether preoperative skin antisepsis actually
      reduces post-operative wound infection and if so which antiseptic is most
      effective. OBJECTIVES: To determine whether preoperative skin antisepsis reduces
      post-operative surgical wound infection. SEARCH STRATEGY: We searched the
      Cochrane Wounds Group Specialised Trials Register and the Cochrane Central
      Register of Controlled Trials in April 2004. In addition we handsearched
      journals, conference proceedings and bibliographies. SELECTION CRITERIA:
      Randomised controlled trials evaluating the use of preoperative skin antiseptics
      applied immediately prior to incision in clean surgery. There were no
      restrictions based on language, date or publication status. DATA COLLECTION AND
      ANALYSIS: Three reviewers independently undertook data extraction and assessment
      of study quality. Pooling was inappropriate and trials are discussed in a
      narrative review. MAIN RESULTS: We identified six eligible RCTs evaluating
      preoperative antiseptics. There was significant heterogeneity in the comparisons
      and the results could not be pooled. In one study, infection rates were
      significantly lower when skin was prepared using chlorhexidine compared with
      iodine. There was no evidence of a benefit in four trials associated with the use
      of iodophor impregnated drapes. REVIEWERS' CONCLUSIONS: There is insufficient
      research examining the effects of preoperative skin antiseptics to allow
      conclusions to be drawn regarding their effects on post-operative surgical wound
      infections. Further research is needed.

PMID- 15266509
TI  - Nasal versus oral route for placing feeding tubes in preterm or low birth weight
      infants.
AB  - BACKGROUND: Enteral feeding tubes for preterm or low birth weight infants may be
      placed via either the nose or mouth. Nasal placement may compromise respiration.
      However, orally placed tubes may be more prone to displacement, local irritation,
      and vagal stimulation. OBJECTIVES: To assess the available evidence from
      randomised controlled trials concerning the effects of nasally placed compared
      with orally placed feeding tubes on growth and development, and the incidence of
      adverse consequences in preterm or low birth weight infants. SEARCH STRATEGY: We
      used the standard search strategy of the Cochrane Neonatal Review Group,
      including electronic searches of the Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 - April
      2004), EMBASE (1988 - April 2004), and CINAHL (1982- April 2004), conference
      proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials that compared the use of the nasal versus oral route
      for placing feeding tubes in preterm or low birth weight infants. DATA COLLECTION
      AND ANALYSIS: We extracted data using the standard methods of the Cochrane
      Neonatal Review Group, with separate evaluation of trial quality and data
      extraction by each author, and analysis of data using relative risk, risk
      difference and mean difference. MAIN RESULTS: We found only one eligible trial.
      Forty-two infants participated in the study. This primary aim of the trial was to
      assess the effect of oral versus nasal placement of feeding tubes on the
      incidence of apnea and periodic breathing in preterm infants. The trial did not
      report data on the pre-specified primary outcomes for this review (growth and
      development). REVIEWERS' CONCLUSIONS: There are insufficient data available to
      inform practice. A large randomised controlled trial is required to determine if
      the use of nasally placed feeding tubes compared with orally placed feeding tubes
      improves growth and development, without increasing adverse consequences in
      preterm or low birth weight infants.

PMID- 15266510
TI  - Placebo interventions for all clinical conditions.
AB  - BACKGROUND: Placebo interventions are often claimed to improve patient-reported
      and observer-reported outcomes, but this belief is not based on evidence from
      randomised trials that compare placebo with no treatment. OBJECTIVES: To assess
      the effect of placebo interventions. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4,
      2002), MEDLINE (1966 to 2002), EMBASE (1980 to 2002), Biological Abstracts (1986
      to 2002), and PsycLIT (1887 to 2002). We contacted experts on placebo research,
      and read references in the included trials. SELECTION CRITERIA: We included
      randomised placebo trials with a no-treatment control group investigating any
      health problem. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial quality and extracted data. We contacted study authors for
      additional information. MAIN RESULTS: Outcome data were available in 156 out of
      182 included trials, investigating 46 clinical conditions. We found no
      statistically significant pooled effect of placebo in 38 studies with binary
      outcomes (4284 patients), relative risk 0.95 (95% confidence interval (CI) 0.89
      to 1.01). The pooled relative risk for patient-reported outcomes was 0.95 (95% CI
      0.88 to 1.03) and for observer-reported outcomes 0.91 (95% CI 0.81 to 1.03).
      There was heterogeneity (P=0.01) but the funnel plot was symmetrical. There was
      no statistically significant effect of placebo interventions in the four clinical
      conditions investigated in three trials or more: pain, nausea, smoking, and
      depression, but confidence intervals were wide. We found an overall effect of
      placebo treatments in 118 trials with continuous outcomes (7453 patients),
      standardised mean difference (SMD) -0.24 (95% CI -0.31 to -0.17). The SMD for
      patient-reported outcomes was -0.30 (95% CI -0.38 to -0.21), whereas no
      statistically significant effect was found for observer-reported outcomes, SMD 
      0.10 (95% CI -0.20 to -0.01). There was heterogeneity (P<0.001) and large
      variability in funnel plot results even for big trials. There was an apparent
      effect of placebo interventions on pain (SMD -0.25 (95% CI -0.35 to-0.16)), and
      phobia (SMD -0.63 (95% CI -1.17 to -0.08)); but also a substantial risk of bias.
      There was no statistically significant effect of placebo interventions in eight
      other clinical conditions investigated in three trials or more: nausea, smoking,
      depression, overweight, asthma, hypertension, insomnia and anxiety, but
      confidence intervals were wide. REVIEWERS' CONCLUSIONS: There was no evidence
      that placebo interventions in general have clinically important effects. A
      possible small effect on continuous patient-reported outcomes, especially pain,
      could not be clearly distinguished from bias.

PMID- 15266511
TI  - Vasectomy occlusion techniques for male sterilization.
AB  - BACKGROUND: Vasectomy is an increasingly popular and effective family planning
      method. A variety of vasectomy techniques are used worldwide including various
      vas occlusion techniques (excision and ligation, thermal or electrocautery, and
      mechanical and chemical occlusion methods), vas irrigation and fascial
      interposition. Vasectomy guidelines largely rely on information from
      observational studies. Ideally, the choice of vasectomy techniques should be
      based on the best available evidence from randomized controlled trials.
      OBJECTIVES: The objective of this review was to compare the effectiveness,
      safety, acceptability and costs of vasectomy techniques for male sterilization.
      SEARCH STRATEGY: We searched the computerized databases the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Popline and LILACS. In
      addition, we searched the reference lists of relevant articles and book chapters.
      SELECTION CRITERIA: We included randomized controlled trials and controlled
      clinical trials comparing vasectomy techniques. DATA COLLECTION AND ANALYSIS: We
      assessed all titles and abstracts located in the literature searches and two
      reviewers independently extracted articles identified for inclusion. Data were
      presented in the text of the review. Outcome measures include contraceptive
      efficacy, safety, discontinuation, and acceptability. MAIN RESULTS: Two trials
      compared vas occlusion with clips versus a conventional vasectomy technique; both
      were of poor quality. Neither trial found a difference between the two groups
      with regard to the primary outcome of failure to reach azoospermia. Four trials
      examined vas irrigation: three compared water irrigation with no irrigation and
      one compared water irrigation with euflavine. All of the trials were of poor
      quality. None of the trials found a significant difference between the groups
      with respect to the primary outcome of time to azoospermia. However, one trial
      found that the median number of ejaculations to azoospermia was significantly
      lower in the euflavine group compared to the water irrigation group. The one
      trial that compared vasectomy with fascial interposition versus vasectomy without
      fascial interposition was a high quality, large study that has only been
      partially reported at the time of this review. The fascial interposition group
      was significantly more likely to be related to vasectomy success (azoospermia) at
      22 weeks. However, fascial interposition also was associated with significantly
      more surgical difficulties. REVIEWERS' CONCLUSIONS: No conclusions can be made
      about the effectiveness, safety, acceptability and costs of vas occlusion
      technique or vas irrigation as studies that examined these were of low quality
      and underpowered. Fascial interposition is associated with improved vasectomy
      success but is associated with some increased surgical difficulty. Randomized
      controlled trials examining other vasectomy techniques were not available. More
      research is required to examine vasectomy techniques.

PMID- 15266512
TI  - Antibiotic prophylaxis in clean and clean-contaminated ear surgery.
AB  - BACKGROUND: Ear surgery may be performed in the treatment of chronic otitis
      media, ossicular chain disorders, tympanic membrane perforations and otitis media
      with effusion. Postoperative infection in ear surgery may result in: Wound
      infections Infection of the middle ear or mastoid resulting in discharge from the
      ear canal Failure of the tympanic membrane to close Labyrinthitis due to
      infection in, or adjacent to, the inner ear These complications may be associated
      with discomfort and inconvenience for the patient, an increase in morbidity and
      an increase in the costs of medical care. OBJECTIVES: The objective of this
      review was to assess the effects of local and/or systemic antibiotics for
      preventing complications such as postoperative discharge, graft failure and
      labyrinthitis in patients undergoing clean or clean-contaminated ear surgery.
      SEARCH STRATEGY: We searched MEDLINE (searched January 1966 to December 2002),
      EMBASE (searched January 1980 to December 2002), the Science Citation Index, The
      Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue
      4 2002); the Cochrane Acute Respiratory Infections Group and Cochrane Ear, Nose
      and Throat Group Specialised Registers and proceedings of scientific meetings.
      The date of the last search was December 2002. We also contacted investigators in
      the field (Govaerts, Antwerp). Bibliographies of identified articles were
      screened for further relevant trials. No language restriction was applied.
      SELECTION CRITERIA: Randomised or quasi-randomised trials involving:
      PARTICIPANTS: patients undergoing clean or clean-contaminated types of ear
      surgery. Skull base surgery was excluded. INTERVENTION: any regimen of local
      and/or systemic antibiotic prophylaxis administered at or around the time of
      surgery compared to placebo, no antibiotic, or an alternative intervention group.
      OUTCOME MEASURES: infection, discharge, graft failure, labyrinthitis, adverse
      effects of prophylaxis. DATA COLLECTION AND ANALYSIS: When possible,
      investigators were contacted for additional information on data and
      methodological issues. At least two reviewers independently extracted data and
      assessed trial quality. MAIN RESULTS: Eleven studies were included in the review.
      The methodological quality of the trials was fair to good. However, most studies
      presented insufficient detail on methodological data. Although definitions of
      outcome measures were heterogeneous, pooling of results was possible. There were
      no significant differences between antibiotic prophylaxis groups and control
      groups in terms of reduction of postoperative infections, graft failures,
      draining outer ear canals and adverse drug effects. REVIEWERS' CONCLUSIONS: There
      is no strong evidence that the large scale use of prophylactic of antibiotics in
      clean and clean-contaminated ear surgery is helpful in reducing postoperative
      complications such as wound infection, discharge from the outer ear canal,
      labyrinthitis and graft failure.

PMID- 15266513
TI  - Glucocorticosteroids for primary sclerosing cholangitis.
AB  - BACKGROUND: Glucocorticosteroids have been suggested for primary sclerosing
      cholangitis, which is characterised by chronic inflammation and fibrosis in the
      intrahepatic and extrahepatic biliary tree. OBJECTIVES: To assess the beneficial
      and harmful effects of glucocorticosteroids for patients with primary sclerosing
      cholangitis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register, The Cochrane Central Register of Controlled Trials on
      The Cochrane Library, MEDLINE, EMBASE from their inception until March 2003, and
      reference lists. SELECTION CRITERIA: Randomised clinical trials comparing any
      dose or duration of glucocorticosteroids versus placebo, no intervention, or
      other immunosuppressive agents. We included trials irrespective of language,
      blinding, or publication status. DATA COLLECTION AND ANALYSIS: Both reviewers
      extracted data independently and assessed the methodological quality by the
      generation of the allocation sequence, allocation concealment, double blinding,
      and follow-up. The results of the meta-analyses were presented as relative risks
      or weighted mean difference (WMD), both with 95% confidence intervals (CI). The
      primary outcome measures were mortality and liver-related morbidity. MAIN
      RESULTS: Two randomised clinical trials were eligible for inclusion. One trial
      compared biliary lavage with hydrocortisone versus saline in 17 patients. A
      significant number of adverse events (pancreatitis; cholangitis with septicaemia;
      paranoid ideas; fluid retention) and no cholangiographic improvement led to
      termination of the trial. The other trial compared budesonide versus prednisone
      in 18 patients. Patients had significantly higher serum bilirubin concentration
      after treatment with prednisone compared with budesonide (WMD 10.4 micro
      mol/litre, 95% CI 1.16 to 19.64 micro mol/litre). No other significant effects on
      clinical or biochemical outcomes were identified for any of the evaluated
      interventions. REVIEWERS' CONCLUSIONS: There is no evidence to support or refute
      peroral glucocorticosteroids for patients with primary sclerosing cholangitis.

PMID- 15266514
TI  - Non-surgical interventions for eosinophilic oesophagitis.
AB  - BACKGROUND: Patients with eosinophilic oesophagitis (EO) present with difficulty
      swallowing, vomiting, regurgitation, chest and/or abdominal pain. People with EO
      frequently fail to respond to treatment with gastric acid suppressants or anti
      reflux surgery. OBJECTIVES: To evaluate the benefits and harms of medical
      interventions for eosinophilic oesophagitis. SEARCH STRATEGY: We searched the
      Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register
      (The Cochrane Library Issue 1, 2004), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February 2004) and
      EMBASE (1980 to February 2004). SELECTION CRITERIA: Randomised controlled trials
      were included if they compared a medical or dietary intervention for eosinophilic
      oesophagitis with a placebo or one medical intervention with another medical
      intervention. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened
      the title of abstracts. MAIN RESULTS: No completed RCTs were found in the
      published literature. We found one abstract reporting preliminary data from an
      RCT (not completed) comparing oral prednisolone with topical (swallowed metered
      dose) fluticasone in children. In this study (50 children enrolled to date)
      healing rates of oesophagitis and symptom resolution with fluticasone were
      similar to those with prednisolone. For another ongoing RCT, comparing the
      efficacy of swallowed fluticasone with placebo for eosinophilic oesophagitis in
      males and females aged 3 to 21 years no results are available. REVIEWERS'
      CONCLUSIONS: The lack of completed RCT's makes it impossible to compare the
      relative benefits and harms of the wide range of medical interventions currently
      used for treating EO. Published case series suggest that an elemental diet, oral
      steroids and topical steroids all offer some benefits. However, lack of a
      comparison group in these studies makes it impossible to evaluate the effect of
      these interventions.

PMID- 15266515
TI  - Maintenance therapy with calcium channel blockers for preventing preterm birth
      after threatened preterm labour.
AB  - BACKGROUND: Calcium channel blocker maintenance therapy is one of the types of
      tocolytic therapy used after an episode of threatened preterm labour (and usually
      an initial dose of tocolytic therapy) in an attempt to prevent the onset of
      further preterm contractions. OBJECTIVES: To assess the effects of calcium
      channel blockers as maintenance therapy on preventing preterm birth after
      threatened preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth Group trials register (31 March 2004); MEDLINE (1966 to March
      2004) and DARE (June 2003). SELECTION CRITERIA: Randomised controlled trials of
      calcium channel blockers used as maintenance therapy to prevent preterm birth
      after threatened preterm labour, compared with alternative drug therapy, placebo
      or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      applied the selection criteria, extracted data from the included study and
      assessed study quality. MAIN RESULTS: One trial of 74 women was included. No
      difference in the incidence of preterm birth was found when calcium channel
      blocker (nifedipine) maintenance therapy was compared with no treatment. Twenty
      five women out of 37 in each group gave birth before 37 weeks (relative risk
      1.00, 95% confidence interval 0.73 to 1.37). The trial did not report stillbirths
      and neonatal deaths prior to discharge. Neurological follow up of the infants was
      not addressed. REVIEWERS' CONCLUSIONS: The role of maintenance therapy with
      calcium channel blockers for preventing preterm birth is not clear. Well designed
      randomised trials of sufficient size with relevant outcomes are required.

PMID- 15266516
TI  - Long-term pharmacotherapy for obesity and overweight.
AB  - BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and
      safe and effective treatment strategies are urgently needed. A number of anti
      obesity agents have been studied in short-term clinical trials, but long-term
      efficacy and safety need to be established. OBJECTIVES: To assess/compare the
      effects and safety of approved anti-obesity medications in clinical trials of at
      least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane
      Controlled Trials Register, the Current Science Meta-register of Controlled
      Trials, and reference lists of original studies and reviews were searched. Date
      of last search was December 2002. Drug manufacturers and two obesity experts were
      contacted in to detect unpublished trials. No language restrictions were imposed.
      SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight
      maintenance trials of approved anti-obesity agents that 1) enrolled adult
      overweight or obese patients, 2) included a placebo control group or compared two
      or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a
      minimum follow-up period of one year. Abstracts and pseudo-randomised trials were
      not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      all potentially relevant citations for inclusion and methodological quality. The
      primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity
      agents investigated, only orlistat and sibutramine trials met inclusion criteria.
      Eleven orlistat weight loss studies (four of which reported a second year weight
      maintenance phase) and five sibutramine studies (three weight loss and two weight
      maintenance trials) were included. Attrition rates averaged 33% during the weight
      loss phase of orlistat trials and 43% in sibutramine studies. All patients
      received lifestyle modification as a co-intervention. Compared to placebo,
      orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI:
      2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95%
      CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The
      number of patients achieving ten percent or greater weight loss was 12% (95% CI:
      8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with
      sibutramine therapy. Weight loss maintenance results were similar. Orlistat
      caused gastrointestinal side effects and sibutramine was associated with small
      increases in blood pressure and pulse rate. REVIEWERS' CONCLUSIONS: Studies
      evaluating the long-term efficacy of anti-obesity agents are limited to orlistat
      and sibutramine. Both drugs appear modestly effective in promoting weight loss;
      however, interpretation is limited by high attrition rates. Longer and more
      methodologically rigorous studies of anti-obesity drugs that are powered to
      examine endpoints such as mortality and cardiovascular morbidity are required to
      fully evaluate any potential benefit of such agents.

PMID- 15266517
TI  - Dietary advice for treatment of type 2 diabetes mellitus in adults.
AB  - BACKGROUND: While initial dietary management immediately after formal diagnosis
      is an 'accepted' cornerstone of treatment of type 2 diabetes mellitus, a formal
      and systematic overview of its efficacy and method of delivery is not currently
      available. OBJECTIVES: To assess the effect of type and frequency of different
      types of dietary advice to all adults with type 2 diabetes on weight, measures of
      diabetic control, morbidity, total mortality and quality of life. SEARCH
      STRATEGY: We carried out a comprehensive search of The Cochrane Library (The
      Cochrane Library Issue 3, 2003), MEDLINE (1966 to October Week 1, 2003), EMBASE
      (1980 to Week 40, 2003), CINAHL (1982 to October Week 1, 2003), AMED (1985 to
      October 2003), bibliographies and contacted relevant experts. SELECTION CRITERIA:
      All randomised controlled trials, of six months or longer, in which dietary
      advice was the main intervention in adults with type 2 diabetes mellitus. DATA
      COLLECTION AND ANALYSIS: The lead investigator performed all data extraction and
      quality scoring with duplication being carried out by one of the other six
      investigators independently with discrepancies resolved by discussion and
      consensus. Authors were contacted for missing data. For continuous outcomes,
      endpoint data were preferred to change data. MAIN RESULTS: Thirty-six articles
      reporting a total of eighteen trials following 1467 participants were included.
      Dietary approaches assessed in this review were low-fat/high-carbohydrate diets,
      high-fat/low-carbohydrate diets, low-calorie (1000 kcal per day) and very-low
      calorie (500 kcal per day) diets and modified fat diets. Two trials compared the
      American Diabetes Association exchange diet with a standard reduced fat diet and
      five studies assessed low-fat diets versus moderate fat or low-carbohydrate
      diets. Two studies assessed the effect of a very-low-calorie diet versus a low
      calorie diet. Six studies compared dietary advice with dietary advice plus
      exercise and three other studies assessed dietary advice versus dietary advice
      plus behavioural approaches. The studies all measured weight and measures of
      glycaemic control although not all studies reported these in the articles
      published. Other outcomes which were measured in these studies included
      mortality, blood pressure, serum cholesterol (including LDL and HDL cholesterol),
      serum triglycerides, maximal exercise capacity and compliance. The results
      suggest that adoption of regular exercise is a good way to promote better
      glycaemic control in type 2 diabetic patients, however all of these studies were
      at high risk of bias. REVIEWERS' CONCLUSIONS: There are no high quality data on
      the efficacy of the dietary treatment of type 2 diabetes, however the data
      available indicate that the adoption of exercise appears to improve glycated
      haemoglobin at six and twelve months in people with type 2 diabetes. There is an
      urgent need for well-designed studies which examine a range of interventions, at
      various points during follow-up, although there is a promising study currently
      underway.

PMID- 15266518
TI  - Non-invasive positive pressure ventilation for treatment of respiratory failure
      due to exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Non-invasive positive pressure ventilation (NPPV) is being used
      increasingly in the management of patients admitted to hospital with acute
      respiratory failure secondary to an exacerbation of chronic obstructive pulmonary
      disease (COPD). OBJECTIVES: To determine the efficacy of NPPV in the management
      of patients with respiratory failure due to an acute exacerbation of COPD. SEARCH
      STRATEGY: An initial search was performed using the Cochrane Airways Group trials
      register and other relevant electronic databases. An updated search was conducted
      in September 2003 and another in April 2004. SELECTION CRITERIA: Randomised
      controlled trials comparing NPPV plus usual medical care (UMC) versus UMC alone
      were selected. Trials needed to recruit adult patients admitted to hospital with
      respiratory failure due to an exacerbation of COPD and with PaCO2 > 6 kPa (45
      mmHg). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected
      articles for inclusion, evaluated methodological quality of the studies and
      abstracted the data. MAIN RESULTS: Fourteen studies were included in the review.
      NPPV resulted in decreased mortality (Relative Risk 0.52; 95%CI 0.35 to 0.76),
      decreased need for intubation (RR 0.41; 95%CI 0.33 to 0.53), reduction in
      treatment failure (RR 0.48; 95%CI 0.37 to 0.63), rapid improvement within the
      first hour in pH (Weight Mean Difference 0.03; 95%CI 0.02 to 0.04), PaCO2 (WMD 
      0.40 kPa; 95%CI -0.78 to -0.03) and respiratory rate (WMD -3.08 bpm; 95%CI -4.26
      to -1.89). In addition, complications associated with treatment (RR 0.38; 95%CI
      0.24 to 0.60) and length of hospital stay (WMD -3.24 days; 95%CI -4.42 to -2.06)
      was also reduced in the NPPV group. REVIEWERS' CONCLUSIONS: Data from good
      quality randomised controlled trials show benefit of NPPV as first line
      intervention as an adjunct therapy to usual medical care in all suitable patients
      for the management of respiratory failure secondary to an acute exacerbation of
      COPD. NPPV should be considered early in the course of respiratory failure and
      before severe acidosis ensues, as a means of reducing the likelihood of
      endotracheal intubation, treatment failure and mortality.

PMID- 15266519
TI  - Ozone therapy for the treatment of dental caries.
AB  - BACKGROUND: Dental caries is a bacterially mediated disease characterised by
      demineralisation of the tooth surface, which may lead to cavitation, discomfort,
      pain and eventual tooth loss. Ozone is toxic to certain bacteria in vitro and it
      has been suggested that delivering ozone into a carious lesion might reduce the
      number of cariogenic bacteria. This possibly could arrest the progress of the
      lesion and may, in the presence of fluoride, perhaps allow remineralisation to
      occur. This may in turn delay or prevent the need for traditional dental
      conservation by 'drilling and filling'. OBJECTIVES: To assess whether ozone is
      effective in arresting or reversing the progression of dental caries. SEARCH
      STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (to 7
      November 2003); Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 3, 2003); MEDLINE and PREMEDLINE (OVID, 1966 to November
      2003); EMBASE (OVID, 1980 to November 2003); CINAHL (OVID, 1982 to November
      2003); AMED (OVID, 1985 to November 2003). Quintessence was handsearched through
      2002 and KaVo were contacted as manufacturers of the HealOzone apparatus for any
      additional published or unpublished trials. SELECTION CRITERIA: Inclusion was
      assessed independently by at least two reviewers. Trials were only included if
      they met the following criteria: randomisation in a controlled trial; single
      surface in vivo carious lesion accessible to ozone application; clear allocation
      concealment; ozone application to the lesions in the intervention group; no such
      application of ozone in the control group; outcomes measured after at least 6
      months. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted
      information in duplicate. A paucity of comparable data did not allow meta
      analytic pooling of the included studies. MAIN RESULTS: Three trials were
      included, with a combined total of 432 randomised lesions (137 participants).
      Forty-two conference papers, abstracts and posters were excluded (from an unknown
      number of studies). The risk of bias in all studies appeared high. The analyses
      of all three studies were conducted at the level of the lesion, which is not
      independent of the person, for this reason pooling of data was not appropriate or
      attempted. Individual studies showed inconsistent effects of ozone on caries,
      across different measures of caries progression or regression. Few secondary
      outcomes were reported, but one trial reported an absence of adverse events.
      REVIEWERS' CONCLUSIONS: Given the high risk of bias in the available studies and
      lack of consistency between different outcome measures, there is no reliable
      evidence that application of ozone gas to the surface of decayed teeth stops or
      reverses the decay process. There is a fundamental need for more evidence of
      appropriate rigour and quality before the use of ozone can be accepted into
      mainstream primary dental care or can be considered a viable alternative to
      current methods for the management and treatment of dental caries.

PMID- 15266520
TI  - Hypnosis for schizophrenia.
AB  - BACKGROUND: Many people with schizophrenia continue to experience symptoms
      despite the use of conventional treatments. Alternative therapies such as
      hypnosis, in conjunction with conventional treatments, may prove beneficial to
      them. OBJECTIVES: To investigate the use of hypnosis for people with
      schizophrenia or schizophrenia-like illnesses compared to standard care and other
      interventions. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's
      Register (January 2003), contacted the Cochrane Complementary Medicine Field for
      additional searching, hand searched references of included or excluded studies
      and made personal contact with authors of relevant trials. SELECTION CRITERIA:
      All randomised or double blind controlled trials that compared hypnosis with
      other treatments or standard care for people with schizophrenia. DATA COLLECTION
      AND ANALYSIS: Studies were reliably selected, quality assessed and data
      extracted. Data were excluded where more than 50% of participants in any group
      were lost to follow up. For binary outcomes we calculated a fixed effects risk
      ratio (RR) and its 95% confidence interval (CI). MAIN RESULTS: We included three
      studies (total n=149). When hypnosis was compared with standard treatment no one
      left between 1-8 weeks (n=70, 2 RCTs, Risk Difference 0.00 CI -0.09 to 0.09).
      Mental state scores were unaffected (n=60, 1 RCT, MD BPRS by 1 week -3.6 CI 
      12.05 to 4.8) as were measures of movement disorders and neurocognitive function.
      Compared with relaxation, hypnosis was also acceptable (n=106, 3 RCTs, RR leaving
      the study early 2.00 CI 0.2 to 2.15) and had no discernable effect on mental
      state (n=60, 1 RCT, MD BPRS by 1 week -3.4 CI -11.4 to 4.6), movement disorders
      or neurocognitive function. Hypnosis was as acceptable as music (Sibelius) by 4
      weeks (n=36, RR leaving the study early 5.0, CI 0.3 to 97.4). REVIEWERS'
      CONCLUSIONS: The studies in this field are few, small, poorly reported and
      outdated. Hypnosis could be helpful for people with schizophrenia but to
      ascertain this requires better designed, conducted and reported randomised
      studies.

PMID- 15266521
TI  - Advanced trauma life support training for hospital staff.
AB  - BACKGROUND: Injury is responsible for an increasing global burden of death and
      disability. As a result, new models of trauma care have been developed. Many of
      these, though initially developed in high-income countries, are now being adopted
      in low and middle-income countries (LMICs). One such trauma care model is
      advanced trauma life support (ATLS) training in hospitals, which is being
      promoted in LMICs as a strategy for improving outcomes for victims of trauma.
      However, the evidence of effectiveness for this health service intervention, in
      either HIC or LMIC settings, has not been rigorously tested using methodology
      such as a systematic review. OBJECTIVES: To quantify the effectiveness of
      hospitals with an ATLS-trained trauma response system versus hospitals without
      such a response system in reducing mortality and morbidity following trauma.
      SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register
      (CIGSR), the Cochrane Controlled Trials Register (CCTR), MEDLINE & PubMed,
      EMBASE, CINAHL, Science Citation Index, National Research Register, and web-based
      trials databases such as Current Controlled Trials. We checked references of
      background papers and contacted authors to identify additional published or
      unpublished data. SELECTION CRITERIA: Randomised controlled trials, controlled
      trials, controlled before- and- after studies comparing effectiveness of
      hospitals with an ATLS-trained trauma response system versus hospitals without
      such a response system in reducing mortality and morbidity following trauma. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria
      to trial reports for inclusion and to extract data. MAIN RESULTS: There is a
      limited literature relating to this topic but none of the studies identified met
      the inclusion criteria for this review. REVIEWERS' CONCLUSIONS: There is no clear
      evidence that ATLS training (or similar) impacts on the outcome for victims of
      trauma, although there is some evidence that educational initiatives improve
      knowledge of what to do in emergency situations. Further, there is no evidence
      that trauma management systems incorporating ATLS training impact positively on
      outcome. Future research should concentrate on the evaluation of trauma systems
      incorporating ATLS, both within hospitals and at the health system level, by
      using rigorous research designs.

PMID- 15266522
TI  - Albumin infusion for low serum albumin in preterm newborn infants.
AB  - BACKGROUND: Intravenous albumin infusion to treat hypoalbuminaemia is used in
      intensive care nurseries. Hypoalbuminaemia occurs in a number of clinical
      situations including prematurity, the acutely unwell infant, respiratory distress
      syndrome (RDS), chronic lung disease (CLD), necrotising enterocolitis (NEC),
      intracranial haemorrhage, hydrops fetalis and oedema. Fluid overload is a
      potential side effect of albumin administration. Albumin is a blood product and
      therefore carries the potential risk of infection and adverse reactions. Albumin
      is also a scarce and expensive resource. OBJECTIVES: The primary objective was to
      assess whether albumin infusions, in preterm neonates with low serum albumin,
      reduces mortality and morbidity. A secondary objective was to assess whether
      albumin infusion is associated with significant side effects. SEARCH STRATEGY:
      Searches were made of MEDLINE from 1966 to April 2004, CINAHL from 1982 to April
      2004 and the current Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library issue 1, 2004). Previous reviews (including cross references)
      and abstracts were also searched. SELECTION CRITERIA: All randomised controlled
      trials in which individual patients were allocated to albumin infusion versus
      control were included. Cross-over studies were excluded. Quasi randomised trials
      were excluded. Participants were preterm infants who had hypoalbuminaemia. Types
      of interventions included albumin infusion versus placebo (e.g. crystalloid) or
      no treatment. DATA COLLECTION AND ANALYSIS: The reviewers worked independently to
      search for trials for inclusion and to assess methodological quality. Studies
      were assessed using the following key criteria: blinding of randomisation,
      blinding of intervention, completeness of follow up and blinding of outcome
      measurement. MAIN RESULTS: Only two small studies were found for inclusion in
      this review and only one reported clinically relevant outcomes - it found no
      significant differences for our primary outcome measure of death (RR 1.5 [95%
      confidence interval 0.3 - 7.43]) or secondary outcome measures of
      intraventricular haemorrhage, patent ductus arteriosus, necrotising
      enterocolitis, bronchopulmonary dysplasia, duration of mechanical ventilation and
      duration of oxygen therapy. REVIEWERS' CONCLUSIONS: There is a lack of evidence
      from randomised trials to determine whether the routine use of albumin infusion,
      in preterm neonates with low serum albumin, reduces mortality or morbidity, and
      no evidence to assess whether albumin infusion is associated with significant
      side effects. There is a need for good quality, double-blind randomised
      controlled trials to assess the safety and efficacy of albumin infusions in
      preterm neonates with low serum albumin.

PMID- 15266523
TI  - Thyroid hormone supplementation for the prevention of morbidity and mortality in
      infants undergoing cardiac surgery.
AB  - BACKGROUND: Paediatric studies have demonstrated that cardiopulmonary bypass is
      associated with a decline in thyroid hormone levels. Adult patients who undergo
      open heart surgery and receive triiodothyronine supplementation have demonstrated
      a dose-dependent increase in cardiac output which has been associated with an
      improved clinical outcome. Thyroid hormone supplementation in infants may also
      reduce post-operative morbidity and mortality. OBJECTIVES: To determine if peri
      operative thyroid hormone supplementation or replacement in infants undergoing
      cardiac surgery on cardiopulmonary bypass improves post-operative and longer term
      morbidity and mortality. SEARCH STRATEGY: The standard search strategy of the
      Cochrane Neonatal Review Group was used. This included searches of The Oxford
      Database of Perinatal Trials, MEDLINE (1966 - December 2003), EMBASE (1980 -
      December 2003), CINAHL (1982 - December 2003), The Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 2, 2003), previous reviews
      including cross references, abstracts, conferences, symposia proceedings, expert
      informants and journal handsearching in the English language. SELECTION CRITERIA:
      All trials using random allocation to peri-operative thyroid hormone therapy
      (supplementation or replacement) compared to control (placebo or no therapy) in
      infants (birth to one year of age) undergoing cardiac surgery requiring
      cardiopulmonary bypass. Thyroid hormone therapy must be tri-iodothyronine. DATA
      COLLECTION AND ANALYSIS: Primary clinical outcomes included measures of post
      operative morbidity and mortality. The standard methods of the Cochrane Neonatal
      Review Group were used in the assessment of trial quality. Treatment effects were
      expressed using relative risk (RR) and mean difference (MD). MAIN RESULTS: Two
      very small studies were identified that tested peri-operative thyroid hormone
      supplementation or replacement in infants aged less than one year undergoing
      cardiac surgery (Chowdhury 2001; Portman 2000). In the Chowdhury 2001 study, a
      subgroup of nine neonates was eligible for this review. No deaths occurred during
      either study. Chowdhury 2001 found no significant effect of peri-operative
      thyroid hormone supplementation in neonates on either length of hospital stay or
      duration of mechanical ventilation. Portman 2000 found no significant difference
      in dopamine requirements for the treatment versus control groups for the first 24
      hours post operatively, while in the Chowdhury neonatal subgroup, inotrope
      requirements were significantly lower in the treatment group. Portman 2000
      reported significant differences between the two groups at 1 and 24 hours post
      operatively for free T3 and at 1 hour post operatively for total T3 levels. Total
      T4 levels showed no significant difference between groups, either pre
      cardiopulmonary bypass or up to 72 hours post operatively. REVIEWERS'
      CONCLUSIONS: At present, there is a lack of evidence concerning the effects of
      tri-iodothyronine supplementation in infants undergoing cardiac surgery. Further
      randomised controlled trials which include sufficiently large subject numbers in
      a variety of different age strata (neonates, infants and older children) need to
      be undertaken.

PMID- 15266524
TI  - Antifungal agents for preventing fungal infections in solid organ transplant
      recipients.
AB  - BACKGROUND: Invasive fungal infections (IFIs) are important causes of morbidity
      and mortality in solid organ transplant recipients. OBJECTIVES: This study aims
      to systematically identify and summarise the effects of antifungal prophylaxis in
      solid organ transplant recipients. SEARCH STRATEGY: The Cochrane Central Register
      of Controlled Trials (Issue 3, 2003), MEDLINE (1966-June 2003), and EMBASE (1980
      June 2003) were searched. Reference lists, abstracts of conference proceedings
      and scientific meetings (1998-2003) were handsearched. Authors of included
      studies and pharmaceutical manufacturers were contacted. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) in all languages comparing the prophylactic
      use of any antifungal agent or regimen with placebo, no antifungal, or another
      antifungal agent or regimen. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently applied selection criteria, performed quality assessment, and
      extracted data using an intention-to-treat approach. Differences were resolved by
      discussion. Data were synthesised using the random effects model and expressed as
      relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Fourteen
      unique trials with 1497 randomised participants were included. Antifungal
      prophylaxis did not reduce mortality (RR 0.90, 95% CI 0.57 to 1.44). In liver
      transplant recipients, a significant reduction in IFIs was demonstrated for
      fluconazole (RR 0.28, 95% CI 0.13 to 0.57). Although less data were available for
      itraconazole and liposomal amphotericin B, indirect comparisons and one direct
      comparative trial suggested similar efficacy. Fluconazole prophylaxis did not
      significantly increase invasive infections or colonisation with fluconazole
      resistant fungi. In renal and cardiac transplant recipients, neither ketoconazole
      nor clotrimazole significantly reduced invasive infections. Overall, the strength
      and precision of comparisons however were limited by a paucity of data.
      REVIEWERS' CONCLUSIONS: For liver transplant recipients, antifungal prophylaxis
      with fluconazole significantly reduces the incidence of IFIs with no definite
      mortality benefit. Given a 10% incidence of IFI, 14 liver transplant recipients
      would require fluconazole prophylaxis to prevent one infection. In transplant
      centres where the incidence of IFIs is high, or in situations where the
      individual risk is great, antifungal prophylaxis should be considered.

PMID- 15266525
TI  - Water for preventing urinary calculi.
AB  - BACKGROUND: Urinary calculi is a common condition characterized of high incidence
      and high recurrence rate. For a long time, increased water intake has been the
      main preventive measure for the disease and its recurrence. OBJECTIVES: To access
      the effectiveness of increased water intake for the primary and secondary
      prevention of urinary calculi. SEARCH STRATEGY: Relevant RCTs were identified by
      electronic and documental searches of MEDLINE, EMBASE, the Chinese Biomedical
      Disk and the Cochrane Central Register of Controlled Trials. No language
      restriction was applied. Date of last search: May 2004. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and quasi-RCTs of increased water intake for
      the prevention of urinary calculi and its recurrence. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and extracted data.
      Statistical analyses were performed using the random effects model and the
      results expressed as relative risk (RR) for dichotomous outcomes or weight mean
      difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN
      RESULTS: No trials of increased water intake for the primary prevention of
      urinary calculi met the inclusion criteria. One trial with 199 patients provided
      results of increased water intake for the recurrence of urinary calculi. The
      recurrence rate was lower in the increased water intake group than that of the no
      intervention group (12% versus 27%, P = 0.008, RR = 0.45, 95% CI 0.24 to 0.84).
      The average interval for recurrences was 3.23 +/-1.1 years in increased water
      intake group and 2.09 +/- 1.37 years in the no intervention group (P = 0.016, WMD
      = 1.14, 95% CI 0.33 to 1.95). REVIEWERS' CONCLUSIONS: The evidence from only one
      trial indicates that increased water intake reduces the risk of recurrence of
      urinary calculi and prolongs the average interval for recurrences. However
      further research is required. Due to the lack of appropriate RCTs, no conclusions
      can be drawn on increased water intake for the primary and secondary prevention
      of urinary calculi.

PMID- 15266526
TI  - Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron
      disease.
AB  - BACKGROUND: Amyotrophic lateral sclerosis, also known as motor neuron disease, is
      a fatal neuromuscular disease characterized by progressive muscle weakness
      resulting in paralysis, which might be treated with ciliary neurotrophic factor.
      OBJECTIVES: The objective of this review was to examine the efficacy of ciliary
      neutrophic factor in amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched
      the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for
      randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from
      January 1980 to October 2003), checked the reference lists of papers identified
      and contacted the authors of studies identified to get additional unpublished
      results. SELECTION CRITERIA: We considered the following selection criteria:
      Types of studies: randomized controlled clinical trials; TYPES OF PARTICIPANTS:
      adults with a diagnosis of either probable or definite amyotrophic lateral
      sclerosis according to the El Escorial criteria; Types of interventions:
      treatment with ciliary neurotrophic factor for at least six months, in a placebo
      controlled randomized format; Types of outcome measures Primary: survival;
      Secondary: muscle strength, respiratory function, changes in bulbar functions,
      changes in quality of life, proportion of patients with adverse side effects
      (such as cough, asthenia, nausea, anorexia, weight loss and increased
      salivation). DATA COLLECTION AND ANALYSIS: We identified two randomized trials.
      The data were extracted and examined independently by the reviewers. Some missing
      data were obtained from investigators. MAIN RESULTS: Two trials, with a total
      population of 1,300 amyotrophic lateral sclerosis patients treated with
      subcutaneous injections of recombinant human ciliary neurotrophic factor, were
      examined in this review. The methodological quality of these trials was
      considered adequate. No significant difference was observed between ciliary
      neurotrophic factor and placebo groups for survival, the primary outcome measure.
      The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences
      between the groups were observed for most of the secondary outcomes. However, a
      significant increase of the incidence of several adverse events was noted in
      groups treated with higher doses of CNTF. REVIEWERS' CONCLUSIONS: Ciliary
      neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis
      progression. At high concentration, several side effects were observed. A
      combination of ciliary neurotrophic factor with other neurotrophic factors (as
      suggested by results on animal models), and more efficient delivery methods
      should be tested.

PMID- 15266527
TI  - Interventions for smokeless tobacco use cessation.
AB  - BACKGROUND: Use of smokeless tobacco (ST) can lead to nicotine addiction and
      health problems including periodontal disease and oral cancer OBJECTIVES: To
      assess the effects of behavioural and pharmacotherapeutic interventions to treat
      ST use. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials
      register (February 2004), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 1, 2004), MEDLINE (January 1966-February
      2004), EMBASE (1988-January 2004), CINAHL (1982-February 2004), PsycINFO (1984
      February 2004), Database of Abstract of Reviews of Effectiveness (DARE, The
      Cochrane Library, Issue 1, 2004). SELECTION CRITERIA: Randomized trials of
      behavioural or pharmacological interventions to help users of ST to quit, with
      follow-up of at least six months. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data. MAIN RESULTS: One trial of bupropion did not detect
      a benefit of treatment after six months (Odds Ratio (OR) 1.00, 95% Confidence
      Interval (CI): 0.23 to 4.37). Three trials of nicotine patch did not detect a
      benefit (OR 1.16, 95% CI: 0.88 to 1.54), nor did two trials of nicotine gum (OR
      0.98, 95% CI: 0.59 to 1.63). There was statistical heterogeneity among the
      results of eight trials of behavioural interventions included in the meta
      analysis. Three trials showed significant benefits of intervention. In a post-hoc
      analysis the trials of interventions which included an oral examination and
      feedback about ST-induced mucosal changes had homogeneous results and when pooled
      showed a significant benefit (OR 2.41 95% CI: 1.79 to 3.24). REVIEWERS'
      CONCLUSIONS: Behavioural interventions should be used to help ST users to quit.
      Pharmacotherapies have not been shown to affect long-term abstinence but larger
      trials are needed.

PMID- 15266529
TI  - Quality of life after rectal resection for cancer, with or without permanent
      colostomy.
AB  - BACKGROUND: For almost one hundred years abdominoperineal excision has been the
      standard treatment of choice for rectal cancer. With advances in the techniques
      for rectal resection and anastomosis, anterior resection with preservation of the
      sphincter function has become the preferred treatment for rectal cancers, except
      for those cancers very close to the anal sphincter. The main reason for this has
      been the conviction that the quality of life for patients with a colostomy after
      abdominoperineal excision was poorer than for patients undergoing a sphincter
      preserving technique. However, patients having sphincter-preserving operations
      may experience symptoms affecting their quality of life that are different from
      those withstoma-patients. OBJECTIVES: To compare the quality of life in rectal
      cancer patients with or without permanent colostomy. SEARCH STRATEGY: We searched
      PubMed, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials
      (CENTRAL), the Cochrane Colorectal Cancer Group's specialised register. Abstracts
      books from major gastroenterological and colorectal congresses were searched.
      Reference lists of the selected articles were scrutinized. SELECTION CRITERIA:
      All controlled clinical trials and observational studies in which quality of life
      was measured in patients with rectal cancer having either abdominoperineal
      excision or low anterior resection, using a validated quality of life instrument,
      were considered. DATA COLLECTION AND ANALYSIS: One reviewer (JP) checked the
      titles and abstracts identified from the databases and hand search. Full text
      copies of all studies of possible relevance were obtained. The reviewer decided
      which studies met the inclusion criteria. Both reviewers independently extracted
      data. If information was insufficient the original author was contacted to obtain
      missing data. Extracted data were crosschecked and discrepancies resolved by
      consensus. MAIN RESULTS: Twenty five potential studies were identified. Eight of
      these, all non-randomised and representing 620 participants, met the inclusion
      criteria. Four trials found that people undergoing abdominoperineal excision did
      not have poorer quality of life measures than patients undergoing anterior
      resection. One study found that a stoma only slightly affected the persons
      quality of life. Three studies found that patients receiving abdominoperineal
      excision had significantly poorer quality of life than after anterior resection.
      Due to heterogeneity, meta-analysis of the included studies was not possible.
      REVIEWERS' CONCLUSIONS: The studies included in this review do not allow firm
      conclusions as to the question of whether the quality of life of people after
      anterior resection is superior to that of people after abdominoperineal excision.
      The included studies challenged the assumption that anterior resection patients
      fare better.Larger, better designed and executed prospective studies are needed
      to answer this question.

PMID- 15266528
TI  - Steroid hormones for contraception in men.
AB  - BACKGROUND: Male hormonal contraception has been an elusive goal. Administration
      of sex steroids to men can shut off sperm production through effects on the
      pituitary and hypothalamus. However, this approach also decreases production of
      testosterone, so "add-back" therapy is needed. OBJECTIVES: To summarize all
      randomized controlled trials of male hormonal contraception. SEARCH STRATEGY: We
      searched the computerized databases Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, Popline, and LILACS (each from inception to
      February, 2003) for randomized controlled trials of hormonal contraception in
      men. We wrote to authors of identified trials to seek unpublished or published
      trials that we might have missed. SELECTION CRITERIA: We included all randomized
      controlled trials in any language that compared a steroid hormone with another
      contraceptive. We excluded non-steroidal male contraceptives, such as gossypol.
      We included both placebo and active-regimen control groups. All trials identified
      included only healthy men with normal semen analyses. DATA COLLECTION AND
      ANALYSIS: Azoospermia (absence of spermatozoa on semen examination) was the
      primary outcome measure. Data were insufficient to examine pregnancy rates and
      side effects. MAIN RESULTS: The proportion of men who achieved azoospermia varied
      widely in reports to date. Few significant differences emerged from these trials.
      Levonorgestrel implants combined with injectable testosterone enanthate (100 mg
      IM) was significantly more effective than was levonorgestrel 125 mcg by mouth
      daily combined with testosterone patches (10 mg/d) (OR for azoospermia with the
      oral levonorgestrel regimen 0.03; 95%CI 0.00-0.29). The addition of
      levonorgestrel 500 mcg by mouth daily improved the effectiveness of testosterone
      enanthate 100 mg IM weekly by itself (OR for azoospermia with the combined
      regimen 4.0; 95%CI 1.00-15.99). Several regimens, including testosterone alone
      and GnRH agonists and antagonists, had disappointing results. REVIEWERS'
      CONCLUSIONS: No male hormonal contraceptive is ready for clinical use. All trials
      published to date have been small exploratory studies. As a result, their power
      to detect important differences has been limited and their results imprecise. In
      addition, the definition of oligospermia has been imprecise or inconsistent in
      many reports. To avoid bias, future trials need more attention to the
      methodological requirements for randomized controlled trials. Trials with
      adequate power would also be helpful.

PMID- 15266530
TI  - Botulinum toxin injections for the treatment of spasmodic dysphonia.
AB  - BACKGROUND: The use of botulinum toxin for the treatment of spasmodic dysphonia
      is currently the treatment of choice for management of this neurological voice
      disorder. Over the past 20 years, botulinum toxin has been used to treat both
      adductor and abductor forms of the disorder, with vocal improvement noted after
      treatment for both. A large number of studies have attempted to document the
      efficacy of botulinum toxin for improvement of vocal symptoms in individuals with
      spasmodic dysphonia. OBJECTIVES: To determine the effectiveness of botulinum
      toxin for treating spasmodic dysphonia. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to July 2003),
      EMBASE (1974 to July 2003 ), CINAHL (through July 2003), Dissertation Abstracts
      International (1975 to July 2003) and PsycINFO (1975 to July 2003). The search
      engine FirstSearch was also used (July 2003). Reference lists for all the
      obtained studies and other review articles were examined for additional studies.
      SELECTION CRITERIA: All studies in which the participants were randomly allocated
      prior to intervention and in which botulinum toxin was compared to either an
      alternative treatment, placebo or non-treated control group were included. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential
      studies meeting the selection criteria noted above for inclusion. One study met
      the inclusion criteria and was included in the final analysis. MAIN RESULTS: Only
      one study in the literature met the inclusion criteria. This was the only study
      identified which reported a treatment/no treatment comparison. It reported
      significant beneficial effects for fundamental frequency (Fo), Fo Range,
      spectrographic analysis, independent ratings of voice severity and patient
      ratings of voice improvement. REVIEWERS' CONCLUSIONS: The evidence from
      randomized controlled trials does not allow firm conclusions to be drawn about
      the effectiveness of botulinum toxin for all types of spasmodic dysphonia, or for
      patients with different behavioral or clinical characteristics.

PMID- 15266531
TI  - Community-based interventions for the prevention of burns and scalds in children.
AB  - BACKGROUND: Burns and scalds are a significant cause of morbidity and mortality
      in children. Successful counter-measures to prevent burn and scald-related injury
      have been identified. However, evidence indicating the successful roll-out of
      these counter-measures into the wider community is lacking. Community-based
      interventions in the form of multi-strategy, multi-focused programmes are
      hypothesised to result in a reduction in population-wide injury rates. This
      review tests this hypothesis with regards to burn and scald injury in children.
      OBJECTIVES: To assess the effectiveness of community-based interventions, defined
      as coordinated, multi-strategy initiatives, for reducing burns and scalds in
      children in children aged 0-14 years. SEARCH STRATEGY: The search strategy was
      based on electronic searches, handsearches of selected journals and snowballing
      from reference lists of selected publications. SELECTION CRITERIA: Studies were
      independently screened for inclusion by two reviewers. Included studies were
      those that reported changes in medically attended burn and scald-related injury
      rates in a paediatric population (age 0 - 14 years), following the implementation
      of a controlled community-based intervention. DATA COLLECTION AND ANALYSIS: Data
      were independently extracted by two reviewers. Meta-analysis was not appropriate,
      due to the heterogeneity of the included studies. MAIN RESULTS: Of 32 identified
      studies, only three met the criteria for inclusion. Only one of these three
      studies showed a significant decrease in paediatric burn and scald injury in the
      intervention community compared with the control community. The failure of the
      other two studies to show a positive result may have been due to limited time
      frame for the intervention and/or failure to adequately implement the counter
      measures in the communities. REVIEWERS' CONCLUSIONS: There are a very limited
      number of research studies allowing conclusions to be drawn about the
      effectiveness of community-based injury prevention programmes to prevent burns
      and scalds in children. There is a pressing need to evaluate high-quality
      community-based intervention programmes based on efficacious counter-measures to
      reduce burns and scalds in children. It is important that a framework for
      considering the problem of burns/scalds in children from a prevention perspective
      be articulated, and that an evidence-based suite of interventions be combined to
      create programme guidelines suitable for implementation in communities throughout
      the world.

PMID- 15266532
TI  - Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the
      treatment of pneumonia in adults.
AB  - BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally
      occurring cytokine that has been shown to increase neutrophil function and
      number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim
      or lenograstim) has found extensive use in the treatment of febrile neutropaenia,
      but its role in the treatment of infection in non-neutropaenic hosts is less well
      defined. OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics
      in the treatment of pneumonia in non-neutropaenic adults. SEARCH STRATEGY: We
      searched the following electronic databases in 2003 and updated the search in
      2004: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 1, 2004); MEDLINE (January 1966 to March Week 1, 2004); EMBASE
      (1998 to December 2003); online databases of clinical trials; and reference lists
      of articles. We also contacted study authors, manufacturers and distributors of G
      CSF. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) which
      included hospitalised adult patients with either community acquired pneumonia or
      hospital-acquired pneumonia. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed trial quality. The primary outcome
      measure was 28 day mortality. Secondary outcome measures included other markers
      of mortality as well as markers of adverse events, including organ dysfunction.
      An assessment of methodological quality was made for each study. MAIN RESULTS:
      Six studies with a total of 1984 people were identified. G-CSF use appeared to be
      safe with no increase in the incidence of total serious adverse events (pooled
      odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ
      dysfunction. However, the use of G-CSF was not associated with improved 28 day
      mortality (pooled OR 0.86; 95% CI: 0.56 to 1.31). REVIEWERS' CONCLUSIONS: There
      is no current evidence supporting the routine use of G-CSF in the treatment of
      pneumonia. Studies in which G-CSF is administered prophylactically or earlier in
      therapy may be of interest.

PMID- 15266533
TI  - Combined oral contraceptive pills for treatment of acne.
AB  - BACKGROUND: Acne is a common skin disorder among women. Although no uniform
      approach to the management of acne exists, combination oral contraceptives
      (COCs), which contain an estrogen and a progestin, often are prescribed for
      women. OBJECTIVES: To determine the effectiveness of COCs for the treatment of
      facial acne compared to placebo or other active therapies. SEARCH STRATEGY: We
      searched the computerized databases Cochrane Skin Group trial register, Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE,
      Biological Abstracts and LILACS for randomized controlled trials of COCs and
      acne. We wrote to authors of identified trials to seek any unpublished or
      published trials that we might have missed. SELECTION CRITERIA: All randomized
      controlled trials reported in any language that compare the effectiveness of a
      COC containing an estrogen and a progestin to placebo or another active therapy
      for acne in women were eligible. DATA COLLECTION AND ANALYSIS: We extracted data
      on total and specific (i.e. open or closed comedones, papules, pustules and
      nodules) facial lesion counts; acne severity grades; global assessments by the
      clinician or the participant and discontinuation due to adverse events. Data were
      entered and analyzed in RevMan 4.2. MAIN RESULTS: The search yielded five placebo
      controlled trials that made three different comparisons and 14 trials that made
      nine comparisons between two COC regimens. An additional trial compared a COC to
      an antibiotic. COCs reduced acne lesion counts, severity grades and self-assessed
      acne compared to placebo. Differences in the comparative effectiveness of COCs
      containing varying progestin types and dosages, though, were less clear. COCs
      that contained chlormadinone acetate or cyproterone acetate improved acne better
      than levonorgestrel although this apparent advantage was based on limited data. A
      COC with cyproterone acetate might result in better acne outcomes than one with
      desogrestrel; however, the three studies comparing these COCs produced
      conflicting results. Likewise, levonorgestrel showed a slight improvement over
      desogestrel in acne outcomes in one trial, but a second trial found no difference
      between the COCs. REVIEWERS' CONCLUSIONS: The three COCs evaluated in placebo
      controlled trials are effective in reducing inflammatory and non-inflammatory
      facial acne lesions. Few differences were found in acne effectiveness between COC
      types. How COCs compare to alternative acne treatments is unknown since limited
      data were available regarding this question.

PMID- 15266534
TI  - Phytomedicines (medicines derived from plants) for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is a common recessively inherited disorder
      of haemoglobin affecting peoples originating from sub-Saharan Africa, the Middle
      East and Mediterranean basin, the Indian subcontinent, the Caribbean and South
      America. The homozygous state (SS) is associated with complications and a reduced
      life expectancy. Phytomedicines (medicine derived from plants in their original
      state) encompass much of what the populations most affected would encounter in
      terms of plant-remedies from traditional healers. There has been little in the
      way of systematic appraisal of their benefits. OBJECTIVES: To assess the benefits
      and risks of phytomedicines in people with SCD of all types, of any age, in any
      setting. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders group specialised register of controlled trials of haemoglobinopathies,
      which comprises references identified from comprehensive electronic database
      searches, handsearches of relevant journals and abstract books of conference
      proceedings. We performed an additional search of the bibliographic database of
      Allied and Complementary Medicine (AMED). Date of most recent search of the
      trials register: September 2003. SELECTION CRITERIA: All randomised or quasi
      randomised trials with participants of all ages with SCD, in all settings,
      comparing the administration of phytomedicines, by any mode to placebo or
      standard treatment, including blood transfusion and hydroxyurea. DATA COLLECTION
      AND ANALYSIS: Both reviewers independently assessed trial quality and extracted
      data from the study. MAIN RESULTS: Reports of two trials were found, of which
      only one, including 82 participants, was eligible for inclusion in this review.
      This Phase IIB (pivotal) study suggests that a phytomedicine, NIPRISAN, was
      effective in reducing episodes of SCD crisis associated with severe pain over a
      six-month period. NIPRISAN did not appear to affect the risk of severe
      complications or the level of anaemia. No serious adverse effects were reported.
      REVIEWERS' CONCLUSIONS: While NIPRISAN, as a phytomedicine, appeared to be safe
      and effective, over a six-month follow-up period of this study, in reducing
      crises associated with severe pain, further studies are required to assess its
      role in the management of people with sickle cell disease. The results of Phase
      III, multicentre trials are awaited.

PMID- 15266535
TI  - Antibiotic prophylaxis for operative vaginal delivery.
AB  - BACKGROUND: Vacuum and forceps assisted vaginal deliveries are reported to
      increase the incidence of postpartum infections and maternal readmission to
      hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are
      prescribed to prevent these infections. However, the benefit of antibiotic
      prophylaxis for operative vaginal deliveries is still unclear. OBJECTIVES: To
      assess the effectiveness and safety of antibiotic prophylaxis in reducing
      infectious puerperal morbidities in women undergoing operative vaginal deliveries
      including vacuum and/or forceps deliveries. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group trials register (November 2003), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,
      2003) and MEDLINE (1966 to November 2003). SELECTION CRITERIA: All randomised
      trials comparing any prophylactic antibiotic regimens with placebo or no
      treatment in women undergoing vacuum or forceps deliveries were eligible.
      Participants were all pregnant women without evidence of infections or other
      indications for antibiotics of any gestational age undergoing vacuum or forceps
      delivery for any indications. Interventions were any antibiotic prophylaxis (any
      dosage regimen, any route of administration or at any time during delivery or the
      puerperium) compared with either placebo or no treatment. DATA COLLECTION AND
      ANALYSIS: Four reviewers assessed trial eligibility and methodological quality.
      Two reviewers extracted the data independently using prepared data extraction
      forms. Any discrepancies were resolved by discussion and a consensus reached
      through discussion with all reviewers. We assessed methodological quality of the
      included trial using the standard Cochrane criteria and the CONSORT statement of
      randomised controlled trials. We calculated the relative risks using a fixed
      effect model and all the reviewers interpreted and discussed the results. MAIN
      RESULTS: One trial, involving 393 women undergoing either vacuum or forceps
      deliveries, was included. This trial identified only two out of the nine outcomes
      specified in this review. It reported seven women with endomyometritis in the
      group given no antibiotic and none in prophylactic antibiotic group. This
      difference did not reach statistical significance, but the relative risk
      reduction was 93% (relative risks 0.07; 95% confidence interval (CI) 0.00 to
      1.21). There was no difference in the length of hospital stay between the two
      groups (weighted mean difference 0.09 days; 95% CI -0.23 to 0.41). REVIEWERS'
      CONCLUSIONS: The data were too few and of insufficient quality to make any
      recommendations for practice. Future research on antibiotic prophylaxis for
      operative vaginal delivery is needed to conclude whether it is useful for
      reducing postpartum morbidity.

PMID- 15266536
TI  - Semen preparation techniques for intrauterine insemination.
AB  - BACKGROUND: Semen preparation techniques for assisted reproduction, including
      intrauterine insemination (IUI), were developed to separate the motile
      morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa
      produce oxygen radicals that negatively influence the ability to fertilize the
      egg. The yield of as many motile, morphologically normal spermatozoa might
      influence treatment choices and therefore outcomes. OBJECTIVES: To compare the
      effectiveness of gradient, swim-up, or wash and centrifugation in subfertile
      couples undergoing intrauterine insemination (IUI) on clinical outcome as well as
      on semen parameters. SEARCH STRATEGY: We searched the Menstrual Disorders and
      Subfertility Group's trials register (30 June 2003), MEDLINE (1966 to July 2003),
      EMBASE (1980 to July 2003), Science Direct Database (1966 to July 2003), Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3,
      2003), National Research Register (2000 to Issue 2, 2003), Biological Abstracts
      (2000 to June 2003), CINAHL (1982 to July 2003) and reference lists of relevant
      articles. We also contacted experts and authors in the field. SELECTION CRITERIA:
      Parallel randomised controlled trials (RCTs), comparing the efficacy of semen
      preparation techniques used for subfertile couples undergoing IUI, were included.
      RCTs or split sample studies examining semen parameters after different semen
      preparation techniques were also included. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and extracted data. Study authors
      were contacted for additional information. MAIN RESULTS: Two randomised
      controlled trials comparing clinical outcomes, including 81 participants in
      total, were included in the meta-analysis (Dodson 1998-I/ II; Xu 2000-I/ II).
      Both studies compared swim-up technique versus gradient technique in 65
      subfertile couples undergoing IUI. One study compared the effectiveness of both
      techniques with wash technique. No trials reported the primary outcome of live
      birth. There was no statistically significant difference between pregnancy rates
      (PR) for swim-up versus gradient / wash centrifuge (Peto OR 0.55, 95% CI 0.17 to
      1.76; Peto OR 1.74, 95% CI 0.2 to 14.9; PR/ couple swim-up 20%, gradient 40%,
      wash 12.5%) or gradient versus wash centrifuge (Peto OR 4.01, 95% CI 0.82 to
      19.56; PR/ couple swim-up 15%, gradient 20%). There was no significant difference
      in the miscarriage rate (MR) per couple between either of the three treatment
      groups in the one trial reporting this outcome (MR/ couple swim-up 0%, gradient
      10.3%, wash 0%. MR/ pregnancy gradient 30.3%). There was no statistically
      significant difference in the multiple pregnancy rate (MPR) per couple between
      either of the three treatment groups in Dodson 1998-I/ II (MPR/ couple swim -up
      0%, gradient 0%, wash 6.3%). One triplet pregnancy was recorded. Fifteen studies
      comparing semen parameters after processing were included. Two studies were
      included in the meta-analysis, we were not able to pool results. REVIEWERS'
      CONCLUSIONS: There is insufficient evidence to recommend any specific preparation
      technique. Large high quality randomised controlled trials, comparing the
      effectiveness of a gradient and/ or a swim-up and/ or wash and centrifugation
      technique on clinical outcome are lacking. Further randomised trials are
      warranted. Results from studies comparing semen parameters may suggest a
      preference for gradient technique, but firm conclusions cannot be drawn and the
      limitations should be taken into consideration.

PMID- 15266537
TI  - Methotrexate for ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of
      unknown cause, characterized by sacroiliitis and spondylitis. To date, treatment
      of AS has been limited to the alleviation of symptoms, mainly using non-steroidal
      anti-inflammatory drugs (NSAIDs). For patients refractory or intolerant to
      NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a
      second line approach. Methotrexate (MTX) is currently one of the most widely used
      DMARDs and its efficacy in rheumatoid arthritis (RA) has been confirmed (Suarez
      Almazor 2003). There is uncertainty whether MTX works in the treatment of AS.
      OBJECTIVES: To evaluate the efficacy and toxicity of methotrexate in the
      treatment of ankylosing spondylitis. SEARCH STRATEGY: Relevant randomised and
      quasi-randomised trials in any language were sought using the following sources:
      CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE
      (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June
      Week 3 2003) and the reference section of retrieved articles. SELECTION CRITERIA:
      We evaluated randomised and quasi-randomised trials examining the efficacy of
      methotrexate on AS. DATA COLLECTION AND ANALYSIS: Unblinded trial reports were
      reviewed independently by two reviewers according to the selection criteria.
      Disagreements on the inclusion of the studies were resolved, where necessary, by
      recourse to a third reviewer. The methodological quality of included trials were
      independently assessed by the same reviewers on randomization, concealment,
      blindness (participants, care providers and outcome investigators), description
      of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers
      independently entered the data extracted from the included trials, using RevMan's
      double entry facility. In the absence of significant heterogeneity, results were
      combined using weighted mean difference or standardised mean difference for
      continuous data, and relative risk for dichotomous data. MAIN RESULTS: Two trials
      met the inclusion criteria. Altan 2001compared naproxen plus MTX (7.5 mg/week
      orally) with naproxen alone and Roychowdhury 2002 compared MTX (10 mg/week
      orally) with placebo. The duration of the trials were 12 months and 24 weeks,
      respectively. They assessed different outcomes except for C-reactive protein
      (CRP). The included trials treated a total of 81 patients and assessed more than
      10 outcomes relevant to the review, covering function, pain, peripheral
      arthritis/enthesitis, morning stiffness, patient and physician global assessment,
      CRP and erythrocyte sedimentation rate (ESR). No significant difference between
      intervention groups was found favouring MTX over no MTX. No serious side effect
      was reported in either trial. REVIEWERS' CONCLUSIONS: There was no statistically
      significant benefit of MTX in the examined outcomes for AS patients. High
      quality, larger sample and longer period of randomized controlled trials
      (possibly with higher dosage of MTX) are needed to verify the uncertainty about
      the efficacy and toxicity of MTX for the treatment of AS.

PMID- 15266538
TI  - Interventions for treating mallet finger injuries.
AB  - BACKGROUND: Mallet finger, also called drop or baseball finger, is where the end
      of a finger cannot be actively straightened out due to injury of the extensor
      tendon mechanism. Treatment commonly involves splintage of the finger for six or
      more weeks. Less frequently, surgical fixation is used to correct the deformity.
      OBJECTIVES: To examine the evidence for the relative effectiveness of different
      methods of treating mallet finger injuries. SEARCH STRATEGY: We searched the
      Cochrane Musculoskeletal Injuries Group trials register (November 2003), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1,
      2004), MEDLINE (1966 to February week 2 2004), EMBASE (1988 to 2004 week 8),
      other databases, reference lists of articles and various conference proceedings.
      SELECTION CRITERIA: Randomised or quasi-randomised clinical trials evaluating
      different interventions, including no intervention, for treating mallet finger
      injuries. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed
      study selection, quality assessment and data extraction. Study authors were
      contacted for additional information. MAIN RESULTS: Four trials were included.
      These involved a total of 278, mainly adult, participants with 283 mallet finger
      injuries. All four trials were methodologically flawed, including inadequate
      outcome assessment. Three trials compared different types of finger splints
      versus a standard Stack splint. One trial found a lower incidence of treatment
      failure in participants treated with a perforated custom-made splint. One trial
      found there were fewer complications in participants treated with a padded
      aluminium-alloy malleable finger splint; however, the incidence of treatment
      failure was similar in the two treatment groups. One trial evaluating the Abouna
      splint found a similar incidence of treatment failure in the two groups. However,
      the Abouna splint often needed replacing due to disintegration of its rubber
      cover and rusting of the exposed wires and was also less popular with
      participants. The fourth trial found no statistically significant differences
      between participants whose mallet finger was treated with Kirschner wire fixation
      and those with a Pryor and Howard splint. Similar numbers had complications in
      the two groups. REVIEWERS' CONCLUSIONS: There was insufficient evidence from
      comparisons tested within randomised trials to establish the relative
      effectiveness of different, either custom-made or off-the-shelf, finger splints
      used for treating mallet finger injury. There was a useful reminder that splints
      used for prolonged immobilisation should be robust enough for everyday use, and
      of the central importance of patient adherence to instructions for splint use.
      There was insufficient evidence to determine when surgery is indicated.

PMID- 15266539
TI  - Prophylactic antibiotics to reduce morbidity and mortality in neonates with
      umbilical artery catheters.
AB  - BACKGROUND: Umbilical artery catheters are often used in unwell neonates.
      Infection related to the use of these catheters may cause significant morbidity
      and mortality. The use of prophylactic antibiotics has been advocated for all
      newborns with umbilical artery catheters in order to reduce the risk of
      colonisation and acquired infection. Countering this is the possibility that harm
      may outweigh benefit. OBJECTIVES: The primary objective was to assess whether
      prophylactic antibiotics, in neonates with umbilical artery catheters, reduce
      mortality and morbidity. In separate comparisons, we planned to review two
      different policies regarding the prophylactic use of antibiotics in neonates with
      umbilical artery catheters: 1) among neonates with umbilical artery catheters, a
      policy of prophylactic antibiotics for the duration of catheterisation (or other
      fixed duration of antibiotic treatment) versus placebo or no treatment; 2) among
      neonates with umbilical artery catheters who had been started on antibiotics at
      the time of catheterisation but whose initial cultures to rule out sepsis are
      negative, a policy of continuing versus discontinuing prophylactic antibiotics.
      SEARCH STRATEGY: We searched MEDLINE (January 1966 to February 2004), CINAHL
      (1982 to February 2004), the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 1, 2004), the Cochrane Neonatal Group
      Specialised Register and reference lists of articles. SELECTION CRITERIA:
      Randomised controlled trials of adequate quality in which newborn infants with
      umbilical artery catheters are randomised to receive prophylactic antibiotics
      versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality. MAIN RESULTS: No study met the criteria for
      inclusion in this review. REVIEWERS' CONCLUSIONS: There is no evidence from
      randomised trials to support or refute the use of prophylactic antibiotics when
      umbilical artery catheters are inserted in newborn infants, or to support or
      refute continuing antibiotics once initial cultures rule out infection in newborn
      infants with umbilical artery catheters.

PMID- 15266540
TI  - Hyperbaric oxygen therapy for thermal burns.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently
      administering 100% oxygen at pressures greater than 1 atmosphere in a pressure
      vessel. This technology has been used to treat a variety of disease states and
      has been described as helping patients who have sustained burns. OBJECTIVES: The
      aim of this review was to assess the evidence for the benefit of hyperbaric
      oxygen treatment (HBOT) for the treatment of thermal burns. SEARCH STRATEGY: We
      searched the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3,
      2002), MEDLINE (Ovid 1966 to November Week 2, 2003), CINAHL (Ovid 1982 to
      December Week 2 2003), EMBASE (Ovid 1980 to September 2003), DORCTHIM (Database
      of Randomised Controlled Trials in Hyperbaric Medicine) from inception to 2003,
      and reference lists of articles. SELECTION CRITERIA: We included all randomised
      controlled trials that compared the effect of HBOT with no HBOT (no treatment or
      sham). DATA COLLECTION AND ANALYSIS: Two authors using standardised forms
      extracted the data independently. Each trial was assessed for internal validity
      with differences resolved by discussion. Data was extracted and entered into
      RevMan 4.2.3. MAIN RESULTS: Four randomised controlled trials were identified, of
      which two satisfied the inclusion criteria. The trials were of poor
      methodological quality. As a result, it was difficult to have confidence in the
      individual results and it would not have been appropriate to attempt to pool the
      data. One trial reported no difference in length of stay, mortality, or number of
      surgeries between the control and HBO-treated groups once these variables were
      adjusted for the patient's condition. The second trial reported mean healing
      times that were shorter in patients exposed to HBOT (mean: 19.7 days versus 43.8
      days). REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient
      evidence to support or refute the effectiveness of HBOT for the management of
      thermal burns. Evidence from the two randomised controlled trials is insufficient
      to provide clear guidelines for practice. Further research is needed to better
      define the role of HBOT in the treatment of thermal burns.

PMID- 15266541
TI  - Luteal phase support in assisted reproduction cycles.
AB  - BACKGROUND: The aspiration of the granulosa cells that surround the oocyte and
      the use of gonadotropin releasing hormone agonists (GnRHa) during assisted
      reproduction technology (ART) treatment can interfere with the production, during
      the luteal phase, of progesterone, which is necessary for successful implantation
      of the embryo. Providing hormonal supplementation during the luteal phase with
      either progesterone itself, or human chorionic gonadotropin (hCG), which
      stimulates progesterone production, may improve implantation and, thus, pregnancy
      rates. OBJECTIVES: To determine (1) if luteal phase support after assisted
      reproduction increases the pregnancy rate, (2) the optimal hormone for luteal
      phase support, i.e. hCG, progesterone, or a combination of both, and (3) the
      optimal route of progesterone administration. SEARCH STRATEGY: We searched the
      Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE (1971 to Dec 2003),
      EMBASE (1985 to Dec 2003). We handsearched reference lists of relevant articles
      were scanned, and abstract books from scientific meetings up to December 2003.
      SELECTION CRITERIA: Randomized controlled trials of luteal phase support after
      ART treatment, comparing hCG or progesterone with placebo or no treatment,
      comparing progesterone with hCG, progesterone plus hCG, or progesterone plus
      estrogen, or comparing different routes of progesterone administration. Quasi
      randomized trials were excluded from the main analyses, but included in a
      secondary analysis for each comparison. DATA COLLECTION AND ANALYSIS: For each
      comparison, data on live birth, ongoing and clinical pregnancy per embryo or
      gamete transfer procedure, miscarriage per clinical pregnancy, ovarian
      hyperstimulation syndrome (OHSS) per transfer, and multiple pregnancy per
      clinical pregnancy were extracted into 2 x 2 tables and subgrouped by use of
      GnRHa in the ovarian stimulation regimen. The odds ratio (OR) and risk difference
      (RD) were calculated. MAIN RESULTS: Fifty-nine studies were included in the
      review. Luteal phase support with hCG provided significant benefit, compared to
      placebo or no treatment, in terms of increased ongoing pregnancy rates (odds
      ratio (OR) 2.38, 95% confidence interval (CI) 1.32 to 4.29) and decreased
      miscarriage rates (OR 0.12, 95% CI 0.03 to 0.50), but only when GnRHa was used.
      The odds of OHSS increased 20-fold when hCG was used in cycles with GnRHa.
      Progesterone use resulted in a small but significant increase in pregnancy rates
      (OR 1.34, 95% CI 1.01 to 1.79) when trials with and without GnRHa were grouped
      together, but no effect on the miscarriage rate was observed. No significant
      difference was found between progesterone and hCG or between progesterone and
      progesterone plus hCG or estrogen in terms of pregnancy or miscarriage rates, but
      the odds of OHSS were more than 2-fold higher with treatments involving hCG than
      with progesterone alone(OR 3.06, 95% CI 1.59 to 5.86). Comparing routes of
      progesterone administration, reductions in clinical pregnancy rate with the oral
      route, compared to the intramuscular or vaginal routes, did not reach statistical
      significance, but there was evidence of benefit of the intramuscular over the
      vaginal route for the outcomes of ongoing pregnancy and live birth. No
      significant difference in pregnancy rate was observed between vaginal
      progesterone gel and other types of vaginal progesterone. REVIEWERS' CONCLUSIONS:
      Luteal phase support with hCG or progesterone after assisted reproduction results
      in an increased pregnancy rate. hCG does not provide better results than
      progesterone, and is associated with a greater risk of OHSS when used with GnRHa.
      The optimal route of progesterone administration has not yet been established.

PMID- 15266542
TI  - Opioid switching to improve pain relief and drug tolerability.
AB  - BACKGROUND: Patients with cancer, and increasingly chronic non-cancer pain
      frequently require strong opioids for pain relief. Morphine is the first-line
      strong opioid of choice for these patients. While most achieve adequate analgesia
      with morphine, a significant minority either suffer intolerable side-effects,
      inadequate pain relief, or both. For these patients switching to an alternative
      opioid is becoming established clinical practice. However, the evidence for the
      effectiveness of opioid switching does not appear to be established. OBJECTIVES:
      The aim of this review was to investigate the usefulness of opioid switching for
      patients with pain. SEARCH STRATEGY: Randomised trials that assessed opioid
      rotation, switching, or substitution in adults or children with acute or chronic
      pain were sought through electronic databases and by handsearching relevant
      journals. Date of the most recent search: January 2003. SELECTION CRITERIA: The
      search strategy retrieved no randomised controlled trials, and therefore no
      studies were available to enable a quantitative synthesis that would assess the
      effectiveness of the strategy of opioid switching. DATA COLLECTION AND ANALYSIS:
      Given the lack of RCTs, the review examined all case reports, uncontrolled, and
      retrospective studies in an attempt to determine the current level of evidence.
      MAIN RESULTS: Fifty-two reports were identified, comprising 23 case reports, 15
      retrospective studies/audits and 14 prospective uncontrolled studies. The
      majority of the reports used morphine as first-line opioid and the most
      frequently used second-line opioid was methadone. All reports, apart from one,
      concluded that opioid switching is a useful clinical manoeuvre for improving pain
      control and/or reducing opioid-related side-effects. REVIEWERS' CONCLUSIONS: For
      patients with inadequate pain relief and intolerable opioid-related
      toxicity/adverse effects, a switch to an alternative opioid may be the only
      option for symptomatic relief. However, the evidence to support the practice of
      opioid switching is largely anecdotal or based on observational and uncontrolled
      studies. Randomised trials, including 'N of 1' studies, where a patient acts as
      their own control, are needed: firstly, to establish the true effectiveness of
      this clinical practice; secondly, to determine which opioid should be used first
      line or second-line; and thirdly, to standardise conversion ratios when switching
      from one opioid to another.

PMID- 15266543
TI  - Common antiepileptic drugs in pregnancy in women with epilepsy.
AB  - BACKGROUND: The potential adverse effects of antiepileptic drug (AED) exposure in
      pregnancy have been well recognised but the relative risks of specific
      antiepileptic drug exposures remain poorly understood. OBJECTIVES: To assess the
      adverse effects of commonly used antiepileptic drugs on maternal and fetal
      outcomes in pregnancy in women with epilepsy. Comparison of outcomes following
      specific antiepileptic drug exposures in utero to unexposed pregnancies in the
      general population or women with epilepsy are described. The current manuscript
      reports the first phase of this review which focuses upon neurodevelopmental
      outcomes in children exposed to antiepileptic drugs in utero. SEARCH STRATEGY: We
      searched MEDLINE, Pharmline, EMBASE, Reprotox and TERIS from 1966 to December
      2003. Review articles and conference abstracts were also hand searched. SELECTION
      CRITERIA: All randomized controlled trials, prospective cohorts of children of
      pregnant women with and without epilepsy and case control studies (cases:
      developmental delay or impaired cognitive outcome, control: normal development)
      were included. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed
      using an adapted version of the Newcastle-Ottawa Scale. The wide variety of
      outcome measures and methodological approaches made meta-analysis difficult and a
      descriptive analysis of the results is presented. MAIN RESULTS: PART A 1b -
      DEVELOPMENTAL OUTCOMES: The majority of studies were of limited quality. There
      was little evidence about which specific drugs carry more risk than others to the
      development of children exposed in utero. The results between studies are
      conflicting and while most failed to find a significant detrimental outcome with
      in utero exposure to monotherapy with carbamazepine, phenytoin or phenobarbitone,
      this should be interpreted cautiously. There were very few studies of exposure to
      sodium valproate. Polytherapy exposure in utero was more commonly associated with
      poorer outcomes, as was exposure to any AEDs when analysis did not take into
      account type of AED. The latter may reflect the large proportion of children
      included in these studies who were in fact exposed to polytherapy. REVIEWERS'
      CONCLUSIONS: PART A 1b - DEVELOPMENTAL OUTCOMES: Based on the best current
      available evidence it would seem advisable for women to continue medication
      during pregnancy using monotherapy at the lowest dose required to achieve seizure
      control. Polytherapy would seem best avoided where possible. More population
      based studies adequately powered to examine the effects of in utero exposure to
      specific monotherapies which are used in everyday practice are required.

PMID- 15266544
TI  - Tai chi for treating rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory
      autoimmune disease that results in the destruction of the musculoskeletal system.
      The major goals of treatment are to relieve pain, reduce inflammation, slow down
      or stop joint damage, prevent disability, and preserve or improve the person's
      sense of well-being and ability to function. Tai Chi, interchangeably known as
      Tai Chi Chuan, is an ancient Chinese health-promoting martial art form that has
      been recognized in China as an effective arthritis therapy for centuries.
      OBJECTIVES: To assess the effectiveness and safety of Tai Chi as a treatment for
      people with RA. SEARCH STRATEGY: We searched the Cochrane Controlled Trials
      Register (CCTR), MEDLINE, Pedro and CINAHL databases up to September 2002, using
      the Cochrane Collaboration search strategy for randomised controlled trials. We
      also searched the Chinese Biomedical Database up to December 2003 and the Beijing
      Chinese Academy of Traditional Medicine up to December 2003. SELECTION CRITERIA:
      Randomized controlled trials and controlled clinical trials examining the
      benefits and harms of exercise programs with Tai Chi instruction or incorporating
      principles of Tai Chi philosophy were selected. We included control groups who
      received no therapy, sham therapy or another type of therapy. DATA COLLECTION AND
      ANALYSIS: Two reviewers determined the studies to be included in this review,
      rated the methodological quality and extracted data using standardized forms.
      MAIN RESULTS: Four trials including 206 participants, were included in this
      review. Tai Chi-based exercise programs had no clinically important or
      statistically significant effect on most outcomes of disease activity, which
      included activities of daily living, tender and swollen joints and patient global
      overall rating. For range of motion, Tai Chi participants had statistically
      significant and clinically important improvements in ankle plantar flexion. No
      detrimental effects were found. One study found that compared to people who
      participated in traditional ROM exercise/rest programs those in a Tai Chi dance
      program reported a significantly higher level of participation in and enjoyment
      of exercise both immediately and four months after completion of the Tai Chi
      program. REVIEWERS' CONCLUSIONS: The results suggest Tai Chi does not exacerbate
      symptoms of rheumatoid arthritis. In addition, Tai Chi has statistically
      significant benefits on lower extremity range of motion, in particular ankle
      range of motion, for people with RA. The included studies did not assess the
      effects on patient-reported pain.

PMID- 15266545
TI  - Psychological interventions for those who have sexually offended or are at risk
      of offending.
AB  - BACKGROUND: Sexual offending is both a social problem and a public health issue.
      To date, no positive treatment effects have been found in quasi-experimental
      institutional treatment programmes. OBJECTIVES: To evaluate effects of
      psychological interventions on target sexual acts, urges or thoughts for people
      who have been convicted, or cautioned, for sexual offences. SEARCH STRATEGY: 33
      electronic databases including the Cochrane Controlled Trials Register (Issue 4,
      2002) were searched. Relevant authors and organisations were contacted for
      additional data. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      involving adults treated in institutional or community settings for sexual
      behaviours that have resulted in conviction or caution for sexual offences, or
      offences or violent behaviours with a sexual element. Behavioural, cognitive
      behavioural, psychodynamic, and psychoanalytic therapies were compared with each
      other, drug treatment, or standard care. DATA COLLECTION AND ANALYSIS:
      Independent assessors selected and assessed studies and extracted data. Data were
      excluded where more than 50% of participants were lost to follow-up. For binary
      outcomes, standard estimations of risk ratio (RR) and their 95% confidence
      intervals (CI) were calculated. Where possible, number-needed-to-treat or harm
      statistics (NNT, NNH) and their 95% CIs were calculated. MAIN RESULTS: We
      included nine RCTs with over 500 male offenders, 231 of whom have been followed
      up for a decade. Cognitive behavioural therapy (CBT) in groups may reduce re
      offence at one year for child molesters when compared with standard care (n=155,
      1 RCT, RR any sexual/violent crime - 0.41 CI 0.2 to 0.82, NNT 6 CI 3 to 20).
      However, when CBT was compared with a trans-theoretical counselling group therapy
      the former may have increased poor attitudes to treatment (corrected n=38, 1 RCT,
      RR 2.8 CI 1.26 to 6.22, NNH 2 CI 1 to 5). The largest trial compared broadly
      psychodynamic group therapy with no treatment for 231 men guilty of paedophilia,
      exhibitionism or sexual assault. Re-arrest over ten years was greater for those
      allocated to group therapy (result not statistically significant [n=231, 1 RCT,
      RR 1.87 CI 0.78 to 4.47]). REVIEWERS' CONCLUSIONS: Limited data make
      recommendations difficult. One study suggests that a cognitive approach results
      in a decline in re-offending after one year. Another large study shows no benefit
      for group therapy and suggests the potential for harm at ten years. The ethics of
      providing this still-experimental treatment to a vulnerable and potentially
      dangerous group of people outside of a well-designed evaluative study are
      debatable. This review proves such studies are possible.

PMID- 15266546
TI  - Progestogens in combined oral contraceptives for contraception.
AB  - BACKGROUND: The progestogen component of oral contraceptives (OC) has undergone
      changes since it was first recognised that their chemical structures could
      influence the spectrum of minor adverse and beneficial effects. The major
      determinants of OCs are effectiveness, cycle control and common side effects. The
      rationale of this review is to provide a systematic comparison of OCs containing
      the progestogens currently in use worldwide. OBJECTIVES: The objective of this
      review is to compare currently available low-dose OCs containing ethinyl
      estradiol and different progestogens in terms of contraceptive effectiveness,
      cycle control, side effects and continuation rates. SEARCH STRATEGY: The Cochrane
      Controlled Trials Register, MEDLINE and EMBASE databases have been searched
      systematically. Relevant pharmaceutical companies and the authors of articles
      included in this review have been contacted for clarification. SELECTION
      CRITERIA: Randomised trials reporting clinical outcomes were considered for
      inclusion. We excluded studies comparing mono- with multiphasic pills, and
      crossover trials with trials in which the difference in total content of ethinyl
      estradiol between preparations exceeded 105 micro g. DATA COLLECTION AND
      ANALYSIS: The methodological quality and validity of studies were assessed based
      on the above-mentioned inclusion criteria. Both application of inclusion criteria
      and data extraction were performed independently by the reviewers. Results are
      expressed as relative risk (RR) with 95% confidence interval (CI) using a random
      effects model. MAIN RESULTS: Twenty-two trials have been included in this review,
      thus generating 14 comparisons. Eighteen trials were sponsored by pharmaceutical
      companies and in only 5 cases had a blind trial been attempted. Most comparisons
      between different interventions included 1-3 trials. There was less
      discontinuation with second- compared to first-generation progestogens (RR: 0.79,
      95% CI: 0.69-0.91). Cycle control appears to be better when using second-
      compared to first-generation progestogens for both mono- (RR: 0.69; 95% CI: 0.52
      0.91) and triphasic (RR: 0.61; 95% CI: 0.43-0.85) preparations.Contraceptive
      effectiveness, spotting, breakthrough bleeding and the absence of withdrawal
      bleeding was similar when using GSD compared to LNG, although there was less
      intermenstrual bleeding in the GSD group (RR: 0.71, 95% CI: 0.55, 0.91).
      Drospirenone (DRSP) appeared to be similar to DSG. REVIEWERS' CONCLUSIONS: Based
      on data from one trial, compared to pills containing LNG, those containing GSD
      may be associated with less intermenstrual bleeding although they show similar
      patterns of spotting, breakthrough bleeding and the absence of withdrawal bleeds.
      GSD is also comparable to DSG. Regarding acceptability, all the indices show that
      third- and second-generation progestogens are preferred over first-generation
      preparations. Future research should focus on independently conducted, well
      designed randomised trials that compare third- and second-generation progestogens
      in particular.

PMID- 15266547
TI  - Glucocorticoids for acute viral bronchiolitis in infants and young children.
AB  - BACKGROUND: Systemic glucocorticoids have been widely prescribed for use in
      infants and young children with acute viral bronchiolitis but the actual benefit
      of this intervention requires clarification. OBJECTIVES: To systematically review
      the evidence on the effectiveness of systemic glucocorticoids for the treatment
      of infants and young children with acute viral bronchiolitis. SEARCH STRATEGY:
      Multiple strategies were incorporated to maximize identification of suitable
      studies. The following databases were searched: the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE
      (January 1966 to September 2003); Current Contents (1998 to 2000); EMBASE
      (January 1990 to September 2003); and Sci Search. Handsearches through cited
      references and contacts with experts were also used. SELECTION CRITERIA: Only
      randomised controlled trials (RCT) were eligible for inclusion. Studies were
      included if participants were diagnosed with acute viral bronchiolitis and
      treated with systemic (oral, intramuscular or intravenous) corticosteroids. Three
      reviewers independently selected potentially relevant articles. Four reviewers
      evaluated these studies, determined eligibility and assessed the methodological
      quality of each RCT. DATA COLLECTION AND ANALYSIS: The primary outcome of
      interest was length of hospital stay (LOS). Secondary outcomes were: respiratory
      rate, haemoglobin oxygen saturation, and hospital admission and revisit rates.
      Data were extracted independently by the four reviewers and the results compiled
      and compared. Two reviewers reassessed studies to clarify points of discrepancy
      in the data extraction and database entry processes. Missing data were requested
      from the authors or calculated from other data presented in the study report.
      MAIN RESULTS: There was complete agreement on the inclusion of 13 trials and the
      exclusion of five studies. Two main study recruitment groups were identified: a)
      infants and young children within the first 48 hours of hospitalisation (10
      trials), and b) outpatient infants and young children who were randomised from
      the emergency department and who may nor may not have required hospital admission
      (three trials).A total of 1,198 children aged 0 to 30 months were treated with
      the equivalent of 0.5 to 10 mg/kg of systemic prednisone for two to seven days.
      Outcomes of interest were not measured in each RCT. In the pooled analysis of
      seven trials, there was a decrease in LOS in treated children of 0.38 days (95%
      confidence interval (CI) -0.81 to 0.05), indicating no significant difference
      between treatment groups. In the pooled analysis of eight trials, the day three
      clinical score measured: a standard mean difference (SMD) of -0.20 (95% CI -0.73
      to 0.32), indicating no difference between treatment groups. Subgroup analyses
      for base LOS and clinical score outcomes were performed on infants who were a)
      less than 12 months of age, b) all respiratory syncytial virus (RSV) positive, c)
      treated with less than 6 mg/kg of prednisone equivalent throughout the illness
      and d) first-time wheezers. These were limited by the small number of studies in
      each subgroup. Hospital admission rates were examined in three trials and no
      difference was seen between treatment groups (odds ratio (OR) 1.05 (95% CI 0.23
      to 4.87). Readmission rates were reported in six studies; with no significant
      differences between treatment groups. Hospital revisit rates were reported in
      three studies, with a significant difference between treatment groups reported in
      one study only. The respiratory rate and haemoglobin oxygen saturation were
      reported descriptively in six RCTs; no differences were found between groups. Co
      interventions (oxygen, supportive fluids and bronchodilators) were used similarly
      between treatment groups in all RCTs. REVIEWERS' CONCLUSIONS: No benefits were
      found in either LOS or clinical score in infants and young children treated with
      systemic glucocorticoids as compared to placebo. There were no differences in
      these outcomes between treatment groups; either in the pooled groups; either in
      the pooled analysis or in any of the sub analyses. Among the three studies
      evaluating hospital admission rates following the initial hospital visit there
      was no difference between treatment groups. There were no differences found in
      respiratory rate, haemoglobin oxygen saturation, hospital revisit or readmission
      rates. Subgroup analyses were significantly limited by the low number of studies
      in each comparison. Marked study heterogeneity and occasionally conflicting
      direction of benefit between trials suggests that these results should be
      interpreted with caution. Specific data on the harm of corticosteroid therapy in
      this patient population are lacking. Available evidence suggests that
      corticosteroid therapy is not of benefit in this patient group.

PMID- 15266548
TI  - TIPS versus paracentesis for cirrhotic patients with refractory ascites.
AB  - BACKGROUND: Ten per cent of cirrhotic patients develop refractory ascites, which
      carries substantial morbidity and has a one-year survival of less than 50 per
      cent. Patients with refractory ascites may benefit from transjugular intrahepatic
      portosystemic stent-shunts (TIPS). OBJECTIVES: To compare TIPS versus
      paracentesis standard treatment in patients with refractory ascites due to
      cirrhosis with regard to overall short- and long-term mortality, treatment
      efficacy, and complications. SEARCH STRATEGY: We searched The Cochrane Hepato
      Biliary Group Controlled Trials Register (July 2003), The Cochrane Central
      Register of Controlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE
      (1966 to July 2003), EMBASE (1980 to July 2003), and CINAHL (1982 to July 2003).
      We supplemented the searches with reading through scientific citations, review of
      citations in relevant primary articles, and hand-searched abstracts from national
      meetings. SELECTION CRITERIA: We included randomised clinical trials comparing
      TIPS and paracentesis with or without volume expanders for cirrhotic patients
      with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the
      methodological quality of the randomised clinical trials by the generation of the
      allocation section, allocation concealment, and follow-up. Two independent
      observers extracted data from each trial. We contacted trial authors for
      additional information. Dichotomous outcomes were reported as odds ratio (OR)
      with 95% confidence interval (CI). MAIN RESULTS: Four randomised clinical trials,
      including 264 patients, met the inclusion criteria. Methodological quality was
      moderate. Thirty-day mortality (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24
      month mortality (OR 1.17, 95% CI 0.52 to 2.66, P = 0.70) did not differ
      significantly between TIPS and paracentesis treatment. TIPS significantly reduced
      ascites re-accumulation at three months (OR 0.07, 95% CI 0.03 to 0.18, P <
      0.00001) and at 12 months follow-up (OR 0.14, 95% CI 0.06 to 0.28, P < 0.00001).
      Hepatic encephalopathy occurred significantly more often in the TIPS group (OR
      2.11, 95% CI 1.22 to 3.66, P = 0.008). Gastrointestinal bleeding (OR 0.82, 95% CI
      0.36 to 1.84, P = 0.63), acute renal failure (OR 0.64, 95% CI 0.15 to 2.72, P =
      0.55), septicemia/infection (OR 1.05, 95% CI 0.22 to 4.94, P = 0.96), and
      disseminated intravascular coagulation (OR 0.82, 95% CI 0.26 to 1.84, P = 0.63)
      did not differ significantly between groups. REVIEWERS' CONCLUSIONS: TIPS removed
      ascites more effectively than paracentesis. After 12 months, the beneficial
      effects of TIPS on ascites was still present. Mortality, gastrointestinal
      bleeding, septicemia/infection, acute renal failure, and disseminated
      intravascular coagulation did not differ significantly between the two groups.
      Hepatic encephalopathy occurred significantly more often in the TIPS group.

PMID- 15266549
TI  - Effect of longer-term modest salt reduction on blood pressure.
AB  - BACKGROUND: Many randomised trials assessing the effect of salt reduction on
      blood pressure show reduction in blood pressure in individuals with high blood
      pressure. However, there is controversy about the magnitude and the clinical
      significance of the fall in blood pressure in individuals with normal blood
      pressure. Several meta-analyses of randomised salt reduction trials have been
      published in the last few years. However, most of these included trials of very
      short duration (e.g. 5 days) and included trials with salt loading followed by
      salt deprivation (e.g. from 20 to 1 g/day) over only a few days. These short-term
      experiments are not appropriate to inform public health policy which is for a
      modest reduction in salt intake over a prolonged period of time. A meta-analysis
      by Hooper et al is an important attempt to look at whether advice to achieve a
      long-term salt reduction (i.e. more than 6 months) in randomised trials causes a
      fall in blood pressure. However, most trials included in this meta-analysis
      achieved a small reduction in salt intake; on average, salt intake was reduced by
      2 g/day. It is, therefore, not surprising that this analysis showed a small fall
      in blood pressure, and that a dose-response to salt reduction was not
      demonstrable. OBJECTIVES: To assess the effect of the currently recommended
      modest reduction in salt intake (WHO 2003; SACN 2003; Whelton 2002), on blood
      pressure in individuals with normal and elevated blood pressure. To assess
      whether the magnitude of the reduction in blood pressure is dependent on the
      magnitude of the reduction in salt intake. SEARCH STRATEGY: We searched MEDLINE,
      EMBASE, Cochrane library, CINAHL, and reference list of original and review
      articles. SELECTION CRITERIA: We included randomised trials with a modest
      reduction in salt intake and a duration of 4 or more weeks. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by two persons. Mean effect sizes
      were calculated using both fixed and random effect models using Review Manager
      4.2.1 software. Weighted linear regression was used to examine the relationship
      between the change in urinary sodium and the change in blood pressure. We used
      funnel plots to detect publication and other biases in the meta-analysis. MAIN
      RESULTS: Seventeen trials in individuals with elevated blood pressure (n=734) and
      11 trials in individuals with normal blood pressure (n=2220) were included. In
      individuals with elevated blood pressure the median reduction in 24-h urinary
      sodium excretion was 78 mmol (4.6 g/day of salt), the mean reduction in systolic
      blood pressure was -4.97 mmHg (95%CI:-5.76 to -4.18), and the mean reduction in
      diastolic blood pressure was -2.74 mmHg (95% CI:-3.22 to -2.26). In individuals
      with normal blood pressure the median reduction in 24-h urinary sodium excretion
      was 74 mmol (4.4 g/day of salt), the mean reduction in systolic blood pressure
      was -2.03 mmHg (95% CI: -2.56 to -1.50) mmHg, and the mean reduction in diastolic
      blood pressure was -0.99 mmHg (-1.40 to -0.57). Weighted linear regression
      analyses showed a correlation between the reduction in urinary sodium and the
      reduction in blood pressure. REVIEWERS' CONCLUSIONS: Our meta-analysis
      demonstrates that a modest reduction in salt intake for a duration of 4 or more
      weeks has a significant and, from a population viewpoint, important effect on
      blood pressure in both individuals with normal and elevated blood pressure. These
      results support other evidence suggesting that a modest and long-term reduction
      in population salt intake could reduce strokes, heart attacks, and heart failure.
      Furthermore, our meta-analysis demonstrates a correlation between the magnitude
      of salt reduction and the magnitude of blood pressure reduction. Within the daily
      intake range of 3 to 12 g/day, the lower the salt intake achieved, the lower the
      blood pressure.

PMID- 15266550
TI  - Decreased plasma membrane targeting of NMDA-NR1 receptor subunit in dendrites of
      medial nucleus tractus solitarius neurons in rats self-administering morphine.
AB  - Opioid abuse is associated with repeated administration and escalation of dose
      that can result in profound adaptations in homeostatic processes. Potential
      cellular mechanisms and neural sites mediating opiate-dependent adaptations may
      involve NMDA-dependent synaptic plasticity within brain areas participating in
      behaviors related to consumption of natural reinforcers, as well as affective
      autonomic integration, notably the medial nucleus tractus solitarius (mNTS). NMDA
      dependent synaptic plasticity may be mediated by changes in the intracellular and
      surface targeting of NMDA receptors, particularly in postsynaptic sites including
      spines or small distal dendrites. High-resolution immunogold electron microscopic
      immunocytochemistry combined with morphometry were used to measure changes in
      targeting of the NMDA-NR1 (NR1) receptor subunit between intracellular and
      plasmalemmal sites in dendrites of neurons of the intermediate mNTS of rats self
      administering escalating doses of morphine (EMSA). In control and EMSA rats, the
      density of plasmalemmal and cytosolic gold particles was inversely related to
      profile size. Collapsed across all NR1-labeled dendrites, rats self-administering
      morphine had a lower number of plasmalemmal gold particles per unit surface area
      (7.1 +/- 0.8 vs. 14.4 +/- 1 per 100 microm), but had a higher number of
      intracellular gold particles per unit cross-sectional area (169 +/- 6.1 vs. 148
      +/- 5.1 per 100 microm2) compared to saline self-administering rats. Morphometric
      analysis showed that the decrease in plasma membrane labeling of NR1 was most
      robust in small dendritic profiles (<1 microm), where there was a reciprocal
      increase in the density of intracellular particles. These results indicate that
      the plasmalemmal distribution of the essential NR1 subunits in distal sites may
      prominently contribute to NMDA receptor-dependent modulation of neural circuitry
      regulating homeostatic processes, and targeting of these proteins can be
      prominently affected by morphine self-administration.

PMID- 15266551
TI  - Activation of 5-HT2 receptors enhances the release of acetylcholine in the
      prefrontal cortex and hippocampus of the rat.
AB  - The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was
      examined in the medial prefrontal cortex and dorsal hippocampus using in vivo
      microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2-
      aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased
      the extracellular concentration of ACh in both brain regions, and this response
      was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3
      mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh
      release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)
      pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in
      both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline
      (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal
      cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM)
      significantly enhanced the release of ACh, and intracortical infusion of LY
      53,857 (100 microM) significantly attenuated this response. These results suggest
      that the release of ACh in the prefrontal cortex and hippocampus is influenced by
      5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the
      prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2
      receptor mechanisms localized within this brain region. Furthermore, it appears
      that the prefrontal cortex is more sensitive than the dorsal hippocampus to the
      stimulatory effect of 5-HT2 agonists on ACh release.

PMID- 15266552
TI  - Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the
      human brain: an immunohistochemical study.
AB  - Two types of cannabinoid receptors have been characterized so far, CB1 and CB2.
      While CB1 receptors are present both in the CNS and in the periphery, CB2
      receptors showed an almost exclusive distribution within the immune system. We
      now report that CB2 receptors are present in a specific microglial cell type of
      the human cerebellum. Thus, we have performed immunohistochemical analysis of
      tissue sections of white matter areas of the human cerebellum and detected the
      presence of CB2 receptors in perivascular microglial cells. These findings match
      with the well-known immunomodulatory role of CB2 receptors and open new
      perspectives on the possible role that these receptors may play in
      pathophysiological events.

PMID- 15266553
TI  - MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation
      with hyperthermia.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine
      and serotonin and evokes hyperthermia which is linked to toxicity for serotonin
      fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain
      have not been described in an animal model of MDMA intoxication. We predicted
      that MDMA-induced hyperthermia should correlate with increased CBF in the
      hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test
      this prediction, we used positron emission tomography with statistical parametric
      mapping for exploratory analysis of the focal changes in the magnitude of CBF in
      the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute
      challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by
      increased CBF in the occipital cortex and in the medial mesencephalon overlapping
      the dorsal raphe nucleus, and reduced CBF in the cerebellar vermis and in a
      cluster in the medulla encompassing the left locus coeruleus. The individual
      increase of body temperature correlated positively with increased CBF in the
      vicinity of the raphe nucleus, in the hypothalamus (regions linked to
      thermoregulation), and also in the medial frontal cortex, which together comprise
      the regions receiving the most dense serotonin innervations in pig brain. Thus,
      individual differences in the susceptibility to MDMA-induced hyperthermia in this
      population correlated with the magnitude of focal increases in CBF within
      specific brain regions endowed with a dense serotonin innervation, including
      regions linked to thermoregulation.

PMID- 15266554
TI  - MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain.
AB  - Positron emission tomography (PET) studies with radiolabeled dopamine D2-like
      receptor ligands reveal d-amphetamine-evoked increases in the competition from
      endogenous dopamine. However, the corresponding effects of
      methylenedioxymethamphetamine (MDMA, "Ecstasy"), which releases catecholamines
      and also serotonin, are unknown. Using PET, we measured the binding potentials
      (pBs) of the benzamide [11C]raclopride and the butyrophenone N
      [11C]methylspiperone ([11C]NMSP) in brain of living pigs first in a baseline
      condition and at 45 and 165 min after infusion of (+/-)-MDMA-HCl (1 mg/kg, i.v.).
      Concomitant studies of cerebral blood flow did not reveal significant perfusion
      changes in the cerebellum reference region or in striatum, supporting the present
      use of reference tissue methods for the mapping of MDMA-evoked pB changes.
      Relative to the baseline pB of [11C]raclopride for dopamine D(2/3) receptors in
      striatum (pB = 1.5-2.2), MDMA-treatment reduced pB by 35% in the first
      posttreatment scan and by 22% in the second posttreatment scan, comparable to
      changes typically evoked by d-amphetamine at a similar dose. In most previous
      studies, the in vivo binding of butyrophenones has been nearly insensitive to d
      amphetamine-evoked dopamine release. However, we found the baseline pB of
      [11C]NMSP for dopamine D2-like receptors in striatum (pB = 4-5) was decreased by
      30% in the first post-MDMA scan and by 50% in the second post-MDMA scan,
      irrespective of assumptions about the extent of equilibrium binding attained
      during the 90-min-long PET recordings. Distinct properties of MDMA such as
      simultaneous release of dopamine and serotonin in brain may account for the
      present finding of progressive decline in the availability of [11C]NMSP binding
      sites in striatum.

PMID- 15266555
TI  - Discrepancy between cell injury and benzodiazepine receptor binding after
      transient middle cerebral artery occlusion in rats.
AB  - We investigated postischemic alterations in benzodiazepine receptor, D1 dopamine
      receptor, and muscarinic acetylcholine receptor binding after transient middle
      cerebral artery (MCA) occlusion in rats using [3H]-flumazenil, [3H]-SCH23390, and
      [3H]-N-methyl-4-piperidyl benzilate ([3H]-NMPB), respectively, as radioligand.
      These ligand bindings were determined at 3 and 24 h and at 3 and 7 days after
      ischemia/reperfusion of MCA by using autoradiographic methods. Ischemic cell
      injury was clearly detected from 3 h after ischemia/reperfusion and progressively
      increased from 3-24 h after ischemia/reperfusion of MCA. The area of cell injury
      reached maximum at 24 h after ischemia/reperfusion of MCA. [3H]-SCH23390 binding
      was reduced to 47% of the contralateral side at 3 days after ischemia/reperfusion
      of MCA. After 7 days, [3H]-SCH23390 binding was further reduced by 20% in the
      striatum. [3H]-NMPB binding was slightly decreased in both the striatum and
      cerebral cortex at 3 days after ischemia/reperfusion of MCA, and [3H]-NMPB
      binding in the striatum and cerebral cortex were reduced to 42 and 62% of the
      contralateral side at 7 days after ischemia/reperfusion of MCA. [3H]-NMPB was
      also decreased at 24 h. In contrast, [3H]-flumazenil binding was not decreased in
      the striatum and cerebral cortex within 7 days after ischemia/reperfusion of MCA.
      These results suggest that [3H]-SCH23390 and [3H]-NMPB binding do not correlate
      with cell injury by ischemia/reperfusion, although vulnerability to
      ischemia/reperfusion was observed with these receptors. In addition, central
      benzodiazepine receptor imaging might be essentially stable to neuronal cell
      injury induced by transient focal cerebral ischemia in rats, in contrast to the
      results of PET studies.

PMID- 15266556
TI  - 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain
      tissue serotonin but not serotonin transporter protein and glial fibrillary
      acidic protein.
AB  - Previous experiments conducted in this laboratory showed that administration of
      high-dose D-fenfluramine (D-FEN) and p-chloroamphetamine (PCA) decreased 5-HT
      transporter (SERT) binding and tissue 5-HT by 30-60% in caudate and whole brain
      tissue 2 days and 2 weeks after drug administration. However, protein expression
      as determined by Western blot analysis did not change in either tissue or time
      point, except for a 30% decrease in the caudate 2 days after PCA administration.
      In the present study, we studied the effect of MDMA and 5,7-dihydroxytryptamine
      (5,7-DHT) on tissue 5-HT levels and the protein expression level of SERT and
      glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker.
      HYPOTHESIS: MDMA administration decreases SERT expression. METHODS: Two weeks
      after MDMA administration (7.5 mg/kg i.p., q 2 h x 3 doses) or 2 weeks after
      i.c.v. administration of 5,7,-DHT (150 microg/rat), male Sprague-Dawley rats were
      sacrificed and the caudate, cortex, and hippocampal tissue collected. Western
      blots for SERT and GFAP were generated using published methods. Tissue 5-HT
      levels were determined by HPLC coupled to electrochemical detection. RESULTS:
      MDMA treatment decreased tissue 5-HT in cortex, hippocampus, and caudate by about
      50%. However, MDMA treatment had no significant effect on expression level of
      SERT and GFAP in any brain region. In contrast, 5,7-DHT reduced tissue 5-HT by
      more than 90%, decreased SERT protein expression by 20-35%, and increased GFAP by
      30-39%. CONCLUSION: These data suggest the MDMA treatment regimen used here does
      not cause degeneration of 5-HT nerve terminals. Viewed collectively with our
      previous results and other published data, these data indicate that MDMA-induced
      persistent 5-HT depletion may occur in the absence of axotomy.

PMID- 15266597
TI  - Astrazon Red dye decolorization by growing cells and pellets of Funalia trogii.
AB  - The dye decolorization activity of fungal pellets has been compared with another
      method based on the decolorization of dye by growing cells. The pellet method was
      more advantageous than the growing cell method. The growing cells of F. trogii
      decolorized 21% of the dye in distilled water medium and 16% in stock basal
      medium in 24 h. On the other hand, Funalia trogii pellets rapidly decolorized the
      Astrazon Red dye, mono-azo textile dye, in 24 h, without any visual sorption of
      any dye to the pellets. The effect of various supplements on longevity of
      decolorization by free pellets was also tested. Glucose and cheese whey
      supplementation improved dye decolorization performance of the pellets and
      remained high and stable for 10 days. We also tested the dye decolorization
      ability of pellets immobilized on activated carbon. These pellets showed the
      stable dye decolorization activity during the repeated batch experiments. The
      study revealed that dye decolorization by pellets is more effective method than
      the growing cell method.

PMID- 15266598
TI  - Entomopathogenic potential of Metarhizium anisopliae isolated from engorged
      females and tested in eggs and larvae of Boophilus microplus (Acari: Ixodidae).
AB  - The purpose of this work was to evaluate the in vitro virulence of three isolates
      of Metarhizium anisopliae var. anisopliae to eggs and larvae of the tick
      Boophilus microplus. The fungus tested was isolated from engorged females of B.
      microplus collected in the field, and identified as Ma01, Ma02 e Ma04. These
      isolates were evaluated by immersion of eggs and larvae in suspension with
      different conidial concentrations: 10(5), 10(6), 10(7) e 10(8) conidia/ml. In
      each isolate there was a treatment group for each spore concentration and a
      control group with 10 repetitions. It was observed in the treated egg groups that
      there was a hatching percentage that was much less than that observed in the
      control groups. This was in inverse proportion to the conidia concentration/ml.
      Larval bioassays of all the tested isolates resulted in a high mortality of
      larvae in direct proportion to the spore concentration/ml, 10 days after the
      conidia suspensions were inoculated. To consolidate the infection, the fungus
      used in bioassays was re-isolated.

PMID- 15266599
TI  - A new microimmunofluorescence test for the detection of Chlamydia pneumoniae
      specific antibodies.
AB  - To evaluate a microimmunofluorescence (MIF) test (Chlamydia pneumoniae IgG,
      Vircell, Spain) that detects IgG against Chlamydophila pneumoniae (Cp), MRL
      Diagnostics MIF was used as reference test. Cross-reactivity against Chlamydia
      trachomatis (Ct) and Chlamydophila psittaci (Cps) was investigated. Eighty sera
      were analysed from 22 subjects with vascular disease, 38 with multiple sclerosis
      and 20 healthy individuals. Vircell and MRL MIF tests assessed 58.75% and 60% of
      the samples as positive, respectively, and their results coincided
      (positive/negative) in 98.75% of samples. One major (>1 IgG titre) and 32 minor
      (1 titre) discrepancies were observed. Correlation between tests was significant.
      Vircell MIF test demonstrated 97.9% sensitivity and 100% specificity. Differences
      in simultaneous reactivity to Ct and Cps between the tests were not significant.
      Vircell MIF test showed a good performance to detect the IgG against Cp.

PMID- 15266600
TI  - Biosynthesis of proteases by Rhizopus oligosporus IHS13 in low-cost medium by
      solid-state fermentation.
AB  - The present study describes the biosynthesis of proteases by a locally isolated
      mould culture of Rhizopus oligosporus IHS13 in a low-cost medium by solid-state
      fermentation technique. The fermentation was carried out in a low-cost medium
      such as sunflower meal, wheat bran and rice bran. Sunflower meal and wheat bran
      in a ratio of 1:1 and moistened with distilled water was found to be the best
      substrate for protease synthesis. All the three substrates are very cheap
      agricultural by-products found in Pakistan. The production of proteases in
      sunflower meal and rice bran was also investigated but the results were
      unsatisfactory. Different cultural conditions such as rate of fermentation,
      effect of incubation temperature, effect of pH and depth of the fermentation
      medium were also optimized. The maximum enzyme synthesis was found after 72 h of
      fermentation at a temperature of 30 degrees C. The optimum pH and depth of the
      medium for protease synthesis were found to be 5.0 and 20 mm respectively. The
      maximum enzyme biosynthesis found during the course of present studies was 7.0 U
      ml(-1).

PMID- 15266601
TI  - Screening of filamentous fungi for the decolorization of a commercial reactive
      dye.
AB  - The aim of this work is to verify the ability of 19 isolates of 13 different
      fungal species to decolorize the reactive dye blue-BF-R. The isolates of
      Pleurotus pulmonarius, P. ostreatus, P. eous, P. citrinopileatus, Lentinus
      edodes, Phanerochaete chrysosporium, Schizophyllum commune, Agaricus blazei,
      Ganoderma sp. and four isolates obtained from textile effluent were evaluated in
      minimum liquid medium. In addition, seven of them were also evaluated on solid
      medium, and both media were both added 0.5 g dye/l. All isolates evaluated on
      solid medium decolorized the dye. The isolates Phanerochaete chrysosporium CCB478
      and Lentinus edodes CCB047 were the ones that presented the fastest and slowest
      growth, respectively. Despite the isolate of the textile effluent had grown on
      solid medium, it did not decolorize the dye. All the isolates of the genus
      Pleurotus, except the isolate Pleurotus eous CCB440, decolorized the dye in
      liquid medium. They presented decolorization percentage ranging from 39% to 51%.
      The absorbance ratio (Abs590/Abs455) of the culture medium inoculated with these
      isolates decreased throughout the experiment indicating the fungal dye
      degradation. The others presented decolorization percent below 8%. The isolates
      of Pleurotus, except the isolate Pleurotus eous CCB440, were able to decolorize
      and to degrade the commercial reactive dye blue-BF-R. The results indicate their
      potential to be used in the treatment of effluents containing this dye.

PMID- 15266602
TI  - Lectin-binding epitopes at the surface of Escherichia coli K-12: examination by
      electron microscopy, with special reference to the presence of a colanic acid
      like polymer.
AB  - The presence and distribution of lectin-binding epitopes at the surface of
      Escherichia coli K-12, strain W1655, was studied by electron microscopy after
      lectin-gold labeling and negative staining. A comparison was made between the
      lectin-binding capacity of cells cultivated at 20 degrees C and 37 degrees C (in
      broth or on agar). A variety of pre-treatment protocols were applied prior to
      labeling. The gold-conjugated lectins used were wheat germ agglutinin (WGA),
      soybean agglutinin (SBA) and Ulex europaeus lectin (UEA-I). For all culture
      conditions, the bacteria had moderate exposure of WGA-binding sites, and this was
      not changed after pre-treatment. Cells cultivated at 37 degrees C had exposed SBA
      and UEA-I-binding epitopes apparently associated with the cell surface. These
      significantly increased in number after boiling the cells for 10 min. With
      bacteria cultivated at 20 degrees C these two lectins recognized sites situated
      on exopolysaccharide filaments. Affino dot-blot experiments with isolated
      polysaccharides of the strain identified the K-12 lipooligosaccharide as the
      source of WGA-binding epitopes, and the exopolysaccharide, colanic acid (CA) as
      the source of SBA- and UEA-I-binding sites. The interaction with these two
      lectins of bacteria cultivated at 37 degrees C could be due to altered
      translocation of CA from the cytoplasm to the environment. This suggestion was
      supported by the demonstration by electron microscopy of SBA and UEA-I binding at
      the surface of hot phenol-water extracted cell walls.

PMID- 15266603
TI  - Influence of growth conditions on the production of a bacteriocin by Lactococcus
      lactis subsp. lactis ST34BR, a strain isolated from barley beer.
AB  - Bacteriocin ST34BR, a small polypeptide of 2.9 kDa produced by Lactococcus lactis
      subsp. lactis ST34BR, inhibits the growth of Enterococcus faecalis, Escherichia
      coli, Lactobacillus plantarum, Lactobacillus casei, Pseudomonas aeruginosa and
      Staphylococcus aureus. MRS broth, adjusted to pH 6.0 yielded 6,400 AU/ml,
      compared to 400 AU/ml recorded in BHI broth, M17 broth, 10% (w/v) soy milk, and
      8% and 10% (w/v) molasses. At pH of 4.5 only 800 AU/ml was produced. Based on
      comparative studies in MRS broth, without organic nitrogen, supplemented with
      different combinations of tryptone, meat extract and yeast extract, tryptone was
      identified as the stimulating nitrogen compound. Growth in the presence of 20 g/l
      glucose, maltose, mannose or sucrose yielded bacteriocin levels of 6,400 AU/ml,
      whereas the same concentration of lactose and fructose yielded 3,200 AU/ml and
      1,600 AU/ml, respectively. No difference in bacteriocin ST34BR activity was
      recorded in MRS broth supplemented with 2 g/l K2HPO4 and 2 g/l, 5 g/l, 10 g/l or
      50 g/l KH2PO4. However, 20 g/l KH2PO4 increased bacteriocin ST34BR production to
      12,800 AU/ml. Glycerol at 1g/l to 10 g/l in MRS broth reduced bacteriocin
      activity to 3,200 AU/ml, whilst 20 g/l and 50 g/l yielded only 1,600 AU/ml. The
      presence of cyanocobalamin, L-ascorbic acid, thiamine and DL-6,8-thioctic acid in
      MRS broth at 1.0 ppm, respectively, did not result in increased activity levels.

PMID- 15266604
TI  - Lignoren, a new sesquiterpenoid metabolite from Trichoderma lignorum HKI 0257.
AB  - The new compound lignoren (1) was isolated from Trichoderma lignorum HKI 0257 by
      chromatographic methods. This metabolite has a santalane-like structure, which
      was elucidated by mass spectrometric and NMR spectroscopic investigations.
      Lignoren (1) shows a moderate narrow-spectrum of antibacterial and antifungal
      activity.

PMID- 15266605
TI  - Isolation of Citrobacter sp. mutants defective in decolorizing malachite green.
AB  - To identify genes involved in the decolorization of malachite green, random
      mutants generated by transposon insertion in the malachite green-decolorizing
      bacterium, Citrobacter sp. were isolated. The resulting mutant bank yielded 24
      mutants with complete defects in their abilities to decolorize malachite green.
      Southern hybridization with a Tn5 fragment as a probe showed a single hybridized
      band in 7 mutants, which appeared to have insertions at different sites of the
      chromosome. The Tn5-inserted genes were isolated and the DNA sequence flanking
      Tn5 was determined. Based on a sequence database, the putative protein products
      encoded by the mg genes were identified as follows. mg3, an ABC transporter
      homolog; mg6, a LysR-type regulatory protein; m11, an oxidoreductase; mg17, a
      MalG protein in the maltose transport system; and mg21, a sugar kinase. The
      deduced sequences from two mg genes (mg7 and mg18) showed no significant
      similarity to any protein with a known function, suggesting that these two mg
      genes encode unidentified proteins that are responsible for the decolorization of
      malachite green.

PMID- 15266606
TI  - Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid
      metabolism in Antley-Bixler syndrome.
AB  - Antley-Bixler syndrome (ABS) is a rare condition characterized by radiohumeral
      synostosis, craniosynostosis, midface hypoplasia, bowing of the femora, multiple
      joint contractures, and urogenital defects. Several reports have implicated
      errors of steroid or sterol metabolism in the pathogenesis of ABS. Evidence for
      this has included association with maternal luteomas, fetal 21-hydroxylase
      deficiency, early pregnancy exposure to high-dose fluconazole, lanosterol 14
      alpha-demethylase deficiency, and a unique urinary steroid profile consistent
      with apparent pregnene hydroxylation deficiency (APHD). We report two sibs with
      classic ABS. During both pregnancies, mid-trimester maternal serum screening
      demonstrated undetectable levels of uncongugated estriol (uE3). The brother had
      ambiguous genitalia and increased serum levels of progesterone and 17-alpha
      hydroxyprogesterone. Postnatal tests performed on the sister demonstrated both
      the unique urinary steroid profile that defines APHD and evidence of impaired
      lanosterol 14-alpha-demethylase activity. Our results suggest that in at least
      some patients with ABS, the skeletal findings and altered steroidogenesis are not
      associated with genes specific to individual sterol or steroid pathways but
      rather are related to an element, such as NADPH cytochrome P450 reductase (CPR)
      or cytochrome b5 (CYb5), that is common to all of these pathways.

PMID- 15266607
TI  - Osteopathia striata with cranial sclerosis: clinical, radiological, and bone
      histological findings in an adolescent girl.
AB  - Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia
      characterized by linear striations of the long bones, osteosclerosis of the
      cranium, and extra-skeletal anomalies. We provide a comprehensive description of
      the skeletal phenotype in a French-Canadian girl with a moderate to severe form
      of sporadic OS-CS. Multiple medical problems, including anal stenosis and the
      Pierre-Robin sequence, were evident in the first few years of life. At 14 years,
      she was fully mobile, with normal intellect and stature. She suffered chronic
      lower extremity pain in the absence of fractures, as well as severe headaches,
      unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical
      indices of bone and mineral metabolism were within normal limits. Bone
      densitometry showed increased areal bone mineral density in the skull, trunk, and
      pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen
      revealed an increased amount of trabecular bone. Trabeculae were abnormally
      thick, but there was no evidence of disturbed bone remodeling. In a cranial bone
      specimen, multiple layers of periosteal bone were found that covered a compact
      cortical compartment containing tightly packed haversian canals. Bone lamellation
      was normal in both the iliac and skull samples. Osteoclast differentiation
      studies showed that peripheral blood osteoclast precursors from this patient
      formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not
      explain why bone mass is increased in most skeletal areas of this patient.
      Cranial histology points to exuberant periosteal bone formation as a potential
      cause of the cranial sclerosis.

PMID- 15266608
TI  - Germline mosaicism resulting in the transmission of severe hemophilia B from a
      grandfather with a mild deficiency.
AB  - We report a family in which the normal pattern of X-linked inheritance of
      hemophilia B (Factor IX deficiency) is complicated by mosaicism in the proband's
      maternal grandfather. The proband, an infant with severe Factor IX deficiency,
      was initially thought to be a sporadic case. Testing of other family members
      identified his mother as a carrier of the disorder, and his asymptomatic maternal
      grandfather as having very mild FIX deficiency. The causative familial mutation
      was identified as a two base pair deletion (AG within codons 134-135) in the
      Factor IX gene. The grandfather was shown to be "heterozygous" for the deletion.
      Karyotype analysis confirmed him to be 46XY thereby ruling out Klinefelter
      syndrome. The proband's aunt, who as the daughter of a man with hemophilia is
      theoretically an obligate carrier, was found not to carry this familial mutation,
      and thus not to be a carrier of hemophilia B. The grandfather must therefore be
      an X chromosome somatic and germline mosaic, with consequent segregation of the
      affected and non-affected Factor IX genes. This observation underlines the
      importance of confirming carrier status even in those individuals assumed to be
      obligate carriers, and has implications for genetic counseling.

PMID- 15266609
TI  - Turner syndrome: evaluation of prenatal diagnosis in 19 European registries.
AB  - This study evaluated the prenatal diagnosis of Turner syndrome by ultrasound
      examination in an unselected population from all over Europe. Data from 19
      congenital malformation registries from 11 European countries were analyzed.
      Turner syndrome was diagnosed in 125 cases (7.2%) in a total of 1,738 chromosome
      abnormalities. Sixty-seven percent of cases were detected prenatally by
      ultrasound examination due to the presence of congenital defects. The most
      frequent anomalies were cystic hygroma (59.5%) and hydrops fetalis (19%). The
      most frequent karyotype was 45,X (81.6%) followed by different types of mosaicism
      (16.8%). Significant differences in congenital defects (P = 0.0003) were observed
      between 45,X karyotypes and 45,X mosaicism cases. Prenatal counseling for 45,X
      mosaicism should take into account the expectation of a milder phenotype. In
      78.6% of cases diagnosed by ultrasound examination due to congenital anomalies,
      the pregnancy was terminated. Prenatal detection of Turner syndrome by ultrasound
      examination was high in this unselected population.

PMID- 15266611
TI  - Ring chromosome 18q and jumping translocation 18p in an adult male with
      hypergonadotrophic hypogonadism.
AB  - Constitutional jumping translocations (JT) are rare, especially in phenotypically
      normal individuals. We report on an adult male with partial hypogonadism as the
      sole phenotypic abnormality with an unusual chromosome abnormality. In this
      patient, centric fission of chromosome 18 lead to formation of a ring 18q
      chromosome, while 18p formed a JT through centromere-telomere fusion with
      chromosome 8q (66%) or 20q (13%). In 21% of cells, the 18p fragment was missing.
      Fluorescent in situ hybridization revealed the presence of interstitial telomeres
      at the junction site of the fusion and unequal distribution of the alphoid
      sequences through the centric fission, leaving a small, yet functional centromere
      within the ring. We discuss the phenotype of the patient in light of this unusual
      karyotype.

PMID- 15266610
TI  - Phenotypic and molecular variability of the holoprosencephalic spectrum.
AB  - Since 1996, a European network has been organized from Rennes, France and
      holoprosencephalic files were collected for clinical and molecular study.
      Familial instances of typical and atypical holoprosencephaly (HPE) were found in
      30% of cases. All affected children had psychomotor delay with microcephaly,
      often associated with endocrine, digestive, and respiratory abnormalities, and
      thermal dysregulation. Among 173 subjects in the molecular study, 28 heterozygous
      mutations were identified (16%): 15 SHH mutations, 6 ZIC2 mutations, 5 SIX3
      mutations, and 2 TGIF mutations.

PMID- 15266612
TI  - Increased prevalence of unprovoked seizures in patients with a 22q11.2 deletion.
AB  - Many neurologic abnormalities have been identified in patients with a deletion of
      chromosome region 22q11.2, including recurrent, apparently unprovoked seizures.
      We reviewed the database of patients with a 22q11.2 deletion at the Children's
      Hospital of Philadelphia to assess the prevalence of idiopathic epilepsy in this
      population. The records of 383 patients with a confirmed 22q11.2 deletion were
      reviewed for documentation of seizures; precipitating events such as
      hypocalcemia, fever, and recent surgery; MRI and EEG findings (to aid in seizure
      classification); and potential risk factors for epilepsy. Of 348 patients with
      adequately detailed histories, 27 patients had apparently unprovoked seizures (7%
      of the total population). A disproportionate number of these patients met
      criteria for generalized epilepsy. Cardiac disease and prematurity were not risk
      factors for the development of unprovoked seizures in this population. The
      prevalence of unprovoked seizures in individuals meeting criteria for epilepsy in
      patients with a 22q11.2 deletion evaluated at our institution is much greater
      than in the general population. The association with generalized epilepsy
      suggests that this increased risk is a primary manifestation of the genetic
      syndrome, not a secondary result of the other manifestations of 22q11.2
      deletions. These results suggest that diagnostic screening for the 22q11.2
      deletion syndrome should be considered in patients with epilepsy and other signs
      suggestive of this interstitial deletion syndrome, and have implications for the
      identification of potential genetic loci for idiopathic epilepsy.

PMID- 15266613
TI  - Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal
      dysplasia patients carrying COMP mutations.
AB  - Mutations in the gene encoding cartilage oligomeric matrix protein (COMP) cause
      two common skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple
      epiphyseal dysplasia (MED). At present, diagnosis of these diseases is based
      primarily on clinical and radiographic findings and is sometimes erroneous,
      particularly in adult patients. However, genetic diagnosis is difficult, because
      COMP mutations are scattered throughout the gene and five additional disease
      genes for MED exist. There is evidence that circulating COMP may serve as a
      molecular indicator of a variety of diseases affecting cartilage. Therefore, we
      investigated plasma COMP concentrations in 21 patients with PSACH or MED. Of
      these, six PSACH and seven MED patients carried COMP mutations, and the remaining
      eight MED patients lacked mutations in COMP. We observed significantly decreased
      plasma COMP levels in patients with COMP mutations compared with controls (P <
      0.0001). In addition, plasma COMP levels were significantly decreased in MED
      patients carrying mutations in COMP relative to those who lacked COMP mutations
      (P = 0.001). Our results indicate that circulating COMP levels reflect genetic
      abnormalities in COMP, providing an easier, more rapid and cost-efficient method
      for diagnosing PSACH and particularly for MED.

PMID- 15266614
TI  - Does bilirubin protect against hemochromatosis gene (HFE) related mortality?
AB  - Serum bilirubin is an important antioxidant that is found at increased levels in
      hereditary hemochromatosis patients. We hypothesized that increased levels of
      serum bilirubin may play a protective role against oxidative stress induced by
      iron overload in carriers of mutations in the hereditary hemochromatosis gene
      (HFE). We studied the relation between serum total bilirubin, serum iron levels,
      the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332
      randomly selected subjects from the Rotterdam Study, a population-based follow-up
      study of people aged 55 years or over. Serum bilirubin levels were significantly
      correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P <
      0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2,
      P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared
      to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or
      homozygotes and C282Y heterozygotes. High levels of serum bilirubin were
      associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D
      homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y
      heterozygotes. Taken together, our data suggest that the high levels of the
      antioxidant bilirubin may counteract the adverse effect of oxidative stress
      induced by iron overload. This may explain in part the reduced penetrance of the
      HFE mutations.

PMID- 15266615
TI  - parkin mutation analysis in clinic patients with early-onset Parkinson
      [corrected] disease.
AB  - parkin Mutations are the most common identified cause of Parkinson's disease
      (PD). It has been suggested that patients with young-onset PD be screened for
      parkin mutations as a part of their clinical work-up. The aim of this study was
      to assess parkin mutation frequency in a clinical setting, correlate genotype
      with phenotype, and evaluate the current justification for clinical parkin
      testing. Patients were selected from a movement disorder clinic based on
      diagnosis of PD and onset age </=40 years. parkin was genotyped by sequence and
      dosage analysis for all 12 exons. Key relatives and controls were screened for
      identified mutations. Mutations were found in 7/39 patients. Two patients were
      compound heterozygous; five were heterozygous. Mutations included deletions in
      exons 2, 3, and 8, duplications in exons 2-4, and 9, and P437L substitution.
      Seventy-eight percent of mutations were deletions/multiplications. A novel
      substitution (R402W) was found in one patient and in one control. None of the
      point mutations found in patients were detected in 96 controls. parkin phenotypes
      were consistent with idiopathic PD. In conclusion, parkin mutations are common in
      the clinic setting: 10% of PD patients had early-onset and 18% of them had parkin
      mutations. However, if parkin is recessive, only 5% of early-onset cases who had
      compound mutations could be attributed to this locus. Mutation frequency was 0.12
      (95% CI 0.04-0.19). parkin cases can present as typical idiopathic PD,
      distinguishable only by molecular testing. Seventy percent of parkin cases were
      heterozygous. It is unclear whether heterozygous mutations are pathogenic. parkin
      based diagnosis and counseling require a better understanding of the mode of
      inheritance, penetrance, and carrier frequencies.

PMID- 15266616
TI  - The 11q terminal deletion disorder: a prospective study of 110 cases.
AB  - We performed a prospective study of 110 patients (75 not previously published)
      with the 11q terminal deletion disorder (previously called Jacobsen syndrome),
      diagnosed by karyotype. All the patients have multiple dysmorphic features.
      Nearly all the patients (94%) have Paris-Trousseau syndrome characterized by
      thrombocytopenia and platelet dysfunction. In total, 56% of the patients have
      serious congenital heart defects. Cognitive function ranged from normal
      intelligence to moderate mental retardation. Nearly half of the patients have
      mild mental retardation with a characteristic neuropsychiatric profile
      demonstrating near normal receptive language ability, but mild to moderate
      impairment in expressive language. Ophthalmologic, gastrointestinal, and
      genitourinary problems were common, as were gross and fine motor delays.
      Infections of the upper respiratory system were common, but no life-threatening
      infections were reported. We include a molecular analysis of the deletion
      breakpoints in 65 patients, from which genetic "critical regions" for 14 clinical
      phenotypes are defined, as well as for the neuropsychiatric profiles. Based on
      these findings, we provide a comprehensive set of recommendations for the
      clinical management of patients with the 11q terminal deletion disorder.

PMID- 15266617
TI  - Endocrine abnormalities in patients with Jacobsen (11q-) syndrome.
AB  - Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is
      caused by the terminal deletion of chromosome 11q. Short stature has been
      reported in this syndrome, however very few of these patients have undergone
      endocrine evaluation. Serum insulin-like growth factor-1 (IGF-1) levels are an
      indirect indicator of growth hormone activity and are a useful initial screening
      tool in the assessment of an individual's growth hormone axis. We studied nine
      children with JS, eight of whom had short stature. Four out of eight children
      with short stature (50%) had low IGF-1 values, with three low for age and one low
      for Tanner stage. Four out of six males (67%) had cryptorchidism, a potential
      sign of hypogonadism. We conclude that low IGF-1 is common in patients with JS
      and short stature, and that growth hormone status and possibly hypothalamic
      pituitary function should be evaluated in this patient population.

PMID- 15266618
TI  - Atypical findings in Kabuki syndrome: report of 8 patients in a series of 20 and
      review of the literature.
AB  - Kabuki syndrome (KS) is a rare multiple congenital anomaly/mental retardation
      syndrome with an estimated frequency of 1/32,000 in Japan. Five major criteria
      delineate KS namely postnatal short stature, skeletal anomalies, moderate mental
      retardation, dermatoglyphic anomalies, and a characteristic facial dysmorphism.
      Here we report on a series of 20 sporadic KS patients and we focus on some rare
      and atypical features that we have observed: chronic and/or severe diarrhea
      (4/20) including celiac disease, diaphragmatic defects (3/20), pseudarthrosis of
      the clavicles (2/20), vitiligo (2/20), and persistent hypoglycemia (2/20). Other
      occasional findings were severe autoimmune thrombopenia, cerebellar vermis
      atrophy, and myopathic features. Interestingly, one of our KS patients presented
      with a clinical overlap with CHARGE syndrome (right eye microphtalmia with optic
      nerve coloboma, VSD, bilateral cryptorchidism, and severe deafness). Because
      these features are more frequent in our series than previously described, we
      propose to carefully investigate these manifestations during KS patient survey in
      an attempt to determine their real frequency and in order to improve clinical
      management.

PMID- 15266619
TI  - A female with complete lack of Mullerian fusion, postaxial polydactyly, and
      tetralogy of fallot: genetic heterogeneity of McKusick-Kaufman syndrome or a
      unique syndrome?
AB  - We report a 19-year-old, non-Amish Caucasian female patient with primary
      amenorrhea caused by complete lack of Mullerian fusion with vaginal agenesis or
      Mullerian aplasia (MA), postaxial polydactyly (PAP), and tetralogy of Fallot. The
      genital tract anomaly of MA with and without renal or skeletal anomalies
      comprises Mayer-Rokitansky-Kuster-Hauser syndrome, which has not been reported
      with tetralogy of Fallot. The phenotypic triad of anomalies most closely
      resembled McKusick-Kaufman syndrome (MKS; OMIM 236700), a rare multiple
      congenital anomaly syndrome comprised of hydrometrocolpos (HMC), PAP, and
      congenital heart malformation that is inherited in an autosomal recessive
      pattern. While upper reproductive tract anomalies have not been reported with
      MKS, they have been reported with Bardet-Biedl syndrome (BBS), a syndrome that
      significantly overlaps with MKS. Both MKS and BBS can be caused by mutations in
      the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with
      mutations in other genes (BBS1, BBS2, BBS4, and BBS7). To address this
      heterogenity, we sequenced the causative genes in MKS and BBS but no mutations in
      these five genes were identified. Fluorescence in situ hybridization (FISH)
      excluded large deletions of chromosome 20p12 and microsatellite marker studies
      confirmed biparental inheritance for all of the known BBS loci. The dual midline
      fusion defects of tetralogy of Fallot and MA suggests that either this patient
      has a unique syndrome with a distinct genetic etiology or that she has a
      genetically heterogeneous or variant form of MKS.

PMID- 15266620
TI  - Newly recognized autosomal recessive acrofacial dysostosis syndrome resembling
      Nager syndrome.
AB  - We report on two patients with a unique constellation of anomalies resembling the
      Nager acrofacial dysostosis syndrome. Clinical manifestations which differentiate
      their condition from Nager syndrome include: microcephaly, cleft lip and palate,
      a peculiar beaked nose, blepharophimosis, microtia, symmetrical involvement of
      the thumbs, and great toes and developmental delay. We postulate that the
      inheritance is autosomal recessive on the basis of similarly affected male and
      female sibs.

PMID- 15266621
TI  - Pregnancy in a healthy woman with untreated citrullinemia.
AB  - We report the clinical and biochemical data on a second successful pregnancy in a
      woman with citrullinemia due to argininosuccinate synthetase deficiency (CTLN1).
      Despite very elevated plasma and urine citrulline and little or no measurable
      argininosuccinate synthetase enzyme activity on cultured skin fibroblasts, this
      29-year-old woman, who was identified through newborn screening, has remained
      asymptomatic throughout her life. Mutation analysis has recently revealed that
      she is a compound heterozygote for a known and a novel mutation (IVS15-1G > C and
      K310Q, respectively). Many newborn screening programs have recently been expanded
      to include citrullinemia and numerous asymptomatic hypercitrullinemic infants and
      children have been identified. It is now important to define prognostic
      indicators that will help with treatment decisions and genetic counseling for
      these patients. This patient, as the only citrullinemic adult who has been
      followed prospectively, contributes important information in this regard. In
      addition, her child was unaffected by the high citrulline levels demonstrated in
      amniotic fluid and breast milk suggesting that citrulline is not teratogenic.
      Although pregnancy is an important risk factor for women with CTLN1, it appears
      that females with citrullinemia can have normal pregnancy outcomes, as long as
      metabolic crisis is avoided.

PMID- 15266622
TI  - Choanal atresia associated with prenatal methimazole exposure: three new
      patients.
AB  - We report three patients with bilateral choanal atresia in children prenatally
      exposed to methimazole (MMI) in order to define a MMI embryopathy clinical
      pattern. The combination of choanal atresia and other specific malformations
      strongly resembles previously reported patients exposed to MMI in utero. At
      present, propylthiouracil is considered the best treatment in pregnancies.
      However in Argentina and some other countries MMI is the only antithyroid drug,
      possibly posing a significant risk to the unborn fetus.

PMID- 15266623
TI  - Czech dysplasia metatarsal type.
AB  - We report three further patients of the recently described new bone dysplasia
      dominantly inherited pseudorheumatoid arthritis. The patients of this report have
      a similar clinical history, the same distinctive phenotype and almost identical
      radiographic findings. The only major difference is absence of weather dependent
      articular pain which characterized the family of the previous study. This report
      expands the clinical data of this bone dysplasia. All patients are Caucasians and
      originate from different parts of the Czech Republic. It seems that this disorder
      is quite a common constitutional bone disorder in this country. We propose the
      name of Czech Dysplasia Metatarsal Type for this unique disease.

PMID- 15266624
TI  - Analysis of the developmental SIX6 homeobox gene in patients with
      anophthalmia/microphthalmia.

PMID- 15266625
TI  - Is brachydactyly type Ballard a variant of brachydactyly type E?

PMID- 15266626
TI  - De novo translocation t(5;18)(q33.1;q12.1) associated with autistic disorder.

PMID- 15266627
TI  - Letter in response to "RNA processing defects of the helicase gene RECQL4 in a
      compound heterozygous Rothmund-Thomson patient" by Beghini et al.

PMID- 15266629
TI  - Advances in understanding and treatment of immune-mediated disorders of the
      peripheral nervous system.
AB  - During recent years, novel insights in basic immunology and advances in
      biotechnology have contributed to an increased understanding of the pathogenetic
      mechanisms of immune-mediated disorders of the peripheral nervous system. This
      increased knowledge has an impact on the management of patients with this class
      of disorders. Current advances are outlined and their implication for therapeutic
      approaches addressed. As a prototypic immune-mediated neuropathy, special
      emphasis is placed on the pathogenesis and treatment of the Guillain-Barre
      syndrome and its variants. Moreover, neuropathies of the chronic inflammatory
      demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed.
      This review summarizes recent progress with currently available therapies and--on
      the basis of present immunopathogenetic concepts--outlines future treatment
      strategies.

PMID- 15266630
TI  - Morvan's syndrome: clinical, laboratory, and in vitro electrophysiological
      studies.
AB  - Morvan's syndrome is a rare disorder characterized by neuromyotonia,
      hyperhidrosis, and central nervous system dysfunction. We report a patient with
      features of this syndrome, but who initially presented with breathing
      difficulties. Concentric needle electromyography showed an abundance of myokymic
      and neuromyotonic discharges. Exercise tests and repetitive nerve stimulation
      showed a decrement-increment response of compound muscle action potentials.
      Antibodies against voltage-gated potassium channels were not detected on repeated
      testing, but the presence of oligoclonal bands in the cerebrospinal fluid (CSF)
      suggested an autoimmune etiology. At follow-up over 3 years, no cancer was found.
      Electrophysiological in vitro studies of effects of patient serum and CSF on rat
      nerves provided no evidence of altered voltage-gated sodium or potassium
      conductances. We conclude that putative humoral factors do not block ion channels
      acutely but may cause channel dysfunction with chronic exposure.

PMID- 15266631
TI  - CASK and Dlg form a PDZ protein complex at the mammalian neuromuscular junction.
AB  - Membrane-associated guanylate kinases (MAGUKs) are modular adapter proteins that
      serve as scaffolding molecules and anchor channels and receptors via their PDZ
      (PSD-95, Dlg, Zo-1) domains. Calcium, calmodulin-associated serine/threonine
      kinase (CASK) is a MAGUK that is critical at synapses in the central nervous
      system and at cell-cell junctions because of its interactions with channels,
      receptors, and structural proteins. We show via confocal microscopy that CASK and
      another MAGUK, Discs Large (Dlg), are present at the mammalian neuromuscular
      junction in skeletal muscle. Immunoprecipitation data from mouse muscle show that
      CASK associates with Dlg, providing evidence of a MAGUK protein complex at this
      synapse. These data indicate that CASK and Dlg may act as a scaffold for
      organizing receptors and channels at the postsynaptic membrane of the
      neuromuscular junction.

PMID- 15266632
TI  - Prediction of voluntary activation, strength and endurance of elbow flexors in
      postpolio patients.
AB  - To examine the long-term effects of polio, maximal voluntary strength and
      voluntary activation of elbow flexor muscles of 177 patients from a postpolio
      clinic were investigated using twitch interpolation. Muscle endurance was studied
      in 142 patients during 45 min of submaximal exercise, and predictors of impaired
      muscle performance were investigated. Twenty-nine of 177 patients (16.4%) had
      impaired voluntary drive to their elbow flexor muscles, but only 16 (9.0%) had
      markedly reduced elbow flexor strength, despite 74 (41.8%) reporting they were
      initially affected in their tested limb and 172 (97.2%) patients reporting new
      generalized symptoms. Seven patients had impaired muscle endurance in the tests
      of strength and voluntary drive. During the submaximal exercise, 16 patients
      (11.3%) had impaired peripheral muscle endurance with normal voluntary
      activation. These results confirm a low incidence of impaired upper-limb muscle
      performance in postpolio patients, despite many patients having subjective
      symptoms consistent with postpolio syndrome. There was an increased relative risk
      for impaired muscle function in those patients with a subjective decrease in
      strength in the tested limb, a recent decline in activities of daily living in
      their tested limb, and who used orthotic devices in their tested limb. Monitoring
      of function in prior-polio patients with impaired muscle performance may be
      useful, particularly when combined with investigation of other potential
      contributory factors to the functional impairment.

PMID- 15266633
TI  - Double-blind randomized controlled trial of low-level laser therapy in carpal
      tunnel syndrome.
AB  - Several studies have suggested that low-level laser therapy (LLLT) is effective
      in patients with carpal tunnel syndrome (CTS). In a double-blind randomized
      controlled trial of LLLT, 15 CTS patients, 34 to 67 years of age, were randomly
      assigned to either the control group (n = 8) or treatment group (n =7). Both
      groups were treated three times per week for 5 weeks. Those in the treatment
      group received 860 nm galium/aluminum/arsenide laser at a dosage of 6 J/cm2 over
      the carpal tunnel, whereas those in the control group were treated with sham
      laser. The primary outcome measure was the Levine Carpal Tunnel Syndrome
      Questionnaire, and the secondary outcome measures were electrophysiological data
      and the Purdue pegboard test. All patients completed the study without adverse
      effects. There was a significant symptomatic improvement in both the control (P =
      0.034) and treatment (P =0.043) groups. However, there was no significant
      difference in any of the outcome measures between the two groups. Thus, LLLT is
      no more effective in the reduction of symptoms of CTS than is sham treatment.

PMID- 15266635
TI  - Ischemia sensitivity and motoneuron afterhyperpolarization in human motor units.
AB  - The purpose of this study was to examine whether motor units, grouped by speed of
      contraction in the human first dorsal interosseous muscle, differed in their
      sensitivity to ischemia and motoneuron afterhyperpolarization (AHP) time-course.
      Motor units were recorded while subjects held an abduction force for
      approximately 10 min. Subsequently, subjects abducted for 4-5 min under ischemic
      conditions. Motor unit twitches derived using spike-triggered averaging were
      allocated into "fast" or "slow" contracting groups based on twitch time to peak
      (TTP) force. Motor units in the "slow" group had a greater sensitivity to
      ischemia than the "fast" group. When upper and lower quartiles of TTP were
      compared, motor units with slow TTP had long AHP time-constants (as estimated by
      an interspike interval histogram transform). Thus, motor units grouped by speed
      of contraction differed in both their sensitivity to ischemia and motoneuron AHP
      time-course. This provides preliminary evidence that the estimated AHP time
      constant may be used to deduce motor-unit type in humans.

PMID- 15266634
TI  - Galvanic vestibular stimulation alters the onset of motor unit discharge.
AB  - We have previously shown that galvanic vestibular stimulation (GVS) can modulate
      the amplitude of the passive soleus H-reflex. This study examined whether the
      response resulted from a general change in excitability of the motoneuron pool or
      a specific modulation of individual motor units (MUs). Subjects performed slow
      isometric plantarflexor actions in a prone lying and kneeling position until the
      discharge of a single gastrocnemius MU was detected. During randomly selected
      trials, a 1-mA bipolar, binaural galvanic stimulus was triggered just prior to
      the start of plantarflexor activity. With the knee extended and the medial
      gastrocnemius (MG) at a long muscle length, GVS did not have an effect on MU
      activity. However, when the knee was flexed and the MG muscle was shortened, GVS
      significantly modified the onset of activation and the initial firing frequency
      of MUs. This may reflect a change in the gain of the presynaptic inhibitory
      mechanisms that act on the motoneuron pool once a muscle reaches a shortened,
      nonoptimal force-producing length. Thus, GVS may provide an important research
      tool for activating descending vestibulospinal pathways that act on lower-limb
      motoneurons and may be applied to test the integrity of the spinal cord.

PMID- 15266636
TI  - Clinical, electrodiagnostic, and sonographic studies in ulnar neuropathy at the
      elbow.
AB  - The aim of this study was to determine possible correlations between the clinical
      characteristics, electrophysiological features, and sonographic ulnar-nerve
      diameter in patients with ulnar neuropathy at the elbow (UNE). We prospectively
      performed clinical, electrodiagnostic, and sonographic studies in 102 patients
      having either purely sensory signs (35%) or sensorimotor signs (65%) of UNE.
      Nerve conduction studies had a sensitivity of 78%, and the addition of sonography
      increased this to 98%. The diagnostic value of both tests was not different among
      cases with and without motor deficit. Motor studies with recording from the
      abductor digiti minimi and first dorsal interosseous muscles were equally
      sensitive for the detection of conduction block or velocity slowing across the
      elbow, but the combination yielded more positive cases than when only one study
      was performed. There were modest negative correlations between the
      electrodiagnostic parameters and the sonographic ulnar-nerve diameter.
      Electrodiagnostically and sonographically, there were no significant differences
      between clinically pure sensory and mixed sensorimotor cases of UNE, except for
      electrodiagnostic findings suggesting loss of motor axons in cases with motor
      signs. Almost half the patients with only sensory signs had electromyographic
      evidence of motor axonal loss. We conclude that, although UNE is clinically
      heterogeneous, the electrophysiological and sonographic findings are fairly
      consistent despite the clinical manifestations.

PMID- 15266637
TI  - Muscle molecular phenotype after stroke is associated with gait speed.
AB  - The disability of patients after stroke is generally attributed to upper motor
      neuron defects, but secondary changes in paretic muscle may enhance the
      disability. We analyzed the molecular phenotype and metabolic profile of the
      paretic and nonparetic vastus lateralis (VL) and we measured the severity of gait
      deficit in 13 patients at least 6 months after ischemic stroke. The results
      showed a significant increase in the proportion of fast myosin heavy chain (MHC,
      68 +/- 14%) in the paretic compared to the nonparetic VL (50 +/- 13%). The
      specific activity of citrate synthase and glyceraldehyde phosphodehydrogenase was
      not significantly different between the two sides. The proportion of fast MHC was
      inversely associated with severity of gait deficit indexed by self-selected
      walking speed in the paretic leg, but not the nonparetic leg. Our findings
      demonstrate significant and potentially modifiable secondary biologic changes in
      hemiparetic muscle phenotype that may contribute to the disability of stroke.

PMID- 15266638
TI  - Encoding of tensile stress and strain during stretch by muscle mechano
      nociceptors.
AB  - Groups III and IV muscle mechano-nociceptors (MNs) can be stimulated during
      noxious stretch, as may occur during hyperextension of a joint. However, the
      mechanical state (characterized by stress and strain) encoded by MNs during
      stretch has not previously been determined. The current study used an ex vivo
      gracilis muscle-nerve preparation in a rat model to apply either a uniform
      uniaxial or pseudo-shear-loading paradigm. Single mechanically sensitive group
      III or IV MNs were mechanically stimulated while plane stress and strain were
      measured at the location of the MN's receptive field. Linear regression was used
      to evaluate the relationships between neural response and mechanical stress and
      strain. The mean neural response (threshold, 47.2 kPa; sensitivity, 0.05 Hz/kPa)
      was highly correlated to tensile stress, tensile strain, and in-plane compressive
      strain but was significantly and substantially less correlated with shear strain.
      Although the overall stress and strain relationship was nonlinear, it was
      reasonably linear (r2 = 0.92) for levels suprathreshold for MNs. Hence, at
      tensile loads sufficient to stimulate MNs, the muscle was acting as a pseudo
      elastic tissue. Thus, muscle MNs encode noxious stretch differently than
      compression and exhibit different encoding of stretch than cutaneous MNs.

PMID- 15266639
TI  - Monocyte/macrophage differentiation in dermatomyositis and polymyositis.
AB  - Recent advances have revealed significant differences in the pathogenesis of
      inflammatory myopathies. To determine whether different patterns of macrophage
      differentiation are a useful tool to delineate the major groups of inflammatory
      myopathies, the muscle biopsies of 11 patients with dermatomyositis and 12
      patients with polymyositis were studied using different macrophage markers. In
      polymyositis, the early-activation markers MRP14 and 27E10 stained the majority
      of macrophages, which were recognized by the pan-macrophage marker Ki-M1P and
      which were located primarily in the endomysium. In dermatomyositis, macrophages
      predominantly expressed the late-activation marker 25F9 and were found mainly in
      the perimysium. Thus, the location and presence of different subsets of
      macrophages distinguish dermatomyositis and polymyositis. The predominance of
      early-activated macrophages in polymyositis indicates a more acute disease
      process. The findings in dermatomyositis, by contrast, suggest a role of
      persistent monocytes/macrophages in the disease process.

PMID- 15266640
TI  - Myasthenia gravis and premature ovarian failure.
AB  - We describe a patient who developed seropositive myasthenia gravis 16 years after
      she was diagnosed with autoimmune premature ovarian failure with antibodies to
      the receptor for follicle-stimulating hormone (FSH). Although thymectomy led to
      improvement of her myasthenic symptoms, menses did not resume. Such combined
      seropositivity for antibodies to acetylcholine and ovarian hormone receptors in a
      patient with myasthenia gravis and premature ovarian failure may reflect common
      disease mechanisms, although the precise pathogenesis of these disorders remains
      ill-defined.

PMID- 15266641
TI  - Effect of size and pressure of surface recording electrodes on amplitude of
      sensory nerve action potentials.
AB  - The influence of electrode size on sensory nerve action potential (SNAP)
      amplitude of the lateral antebrachial cutaneous nerve (LACN) and sural nerve (SN)
      was studied in 63 healthy volunteers. The SNAP amplitudes were measured using
      surface recording electrodes of three different sizes, positioned across the
      nerve. Mean amplitudes using a 5-mm electrode were 9.0% (SN) and 15.3% (LACN)
      higher than with a 20-mm electrode and 19.4% (SN) and 25.8% (LACN) higher than
      using a 40-mm electrode. To study the influence of pressure on surface recording
      electrodes, studies were performed on the LACN in 31 healthy volunteers. Light
      pressure of the recording electrodes on the skin gave lower amplitudes (15.3%)
      than did greater pressure or pressure applied between active and reference
      electrodes. These studies demonstrate that standardized surface recording
      electrode size and pressure are imperative for obtaining valid and reliable
      results in experimental studies or in clinical follow-up of patients undergoing
      nerve conduction studies.

PMID- 15266642
TI  - Bilateral intraneural perineurioma presenting as ulnar neuropathy at the elbow.
AB  - We describe a 36-year-old woman with progressive bilateral ulnar neuropathy.
      Sonographic and magnetic resonance imaging studies revealed extensive focal ulnar
      nerve enlargement at the elbow. Histological studies gave evidence of an
      intraneural perineurioma. Because intraneural perineurioma usually appears as a
      single mass lesion at sites other than typical entrapment sites, this mode of
      presentation is unusual. We discuss the nature of this benign tumor and the
      differential diagnosis of nerve enlargement. Knowledge of possible causes of
      nerve thickening is crucial when performing imaging in patients with
      neuropathies.

PMID- 15266643
TI  - Impact of TNF-alpha blockade on TGF-beta1 and type I collagen mRNA expression in
      dystrophic muscle.

PMID- 15266645
TI  - Characterization of a novel molluskan tyrosine kinase receptor that inhibits
      neurite regeneration.
AB  - Receptor tyrosine kinases play many important roles in neuronal signaling
      including regulating neurite outgrowth. We have identified a novel receptor
      tyrosine kinase, neurite outgrowth regulating kinase (nork) from Aplysia
      californica. A fragment of this kinase was also identified in another mollusk,
      Lymnaea. The kinase domain is equally homologous to the Ret (rearranged during
      transformation) and fibroblast growth factor receptor families, but the
      extracellular domain is entirely novel, suggesting that it binds a nonconserved
      ligand. Overexpression of neurite outgrowth regulating kinase, but not a kinase
      dead form, causes a reduction in neurite outgrowth of Aplysia sensory neurons.
      Thus, we have identified a novel receptor tyrosine kinase implicated in
      regulating neurite outgrowth.

PMID- 15266646
TI  - Survival of mammalian B104 cells following neurite transection at different
      locations depends on somal Ca2+ concentration.
AB  - We report that cell survival after neurite transection in a mammalian neuronal
      model (cultured B104 cells) critically depends on somal [Ca2+]i, a novel result
      that reconciles separate long-standing observations that somal survival decreases
      with more-proximal axonal transections and that increased somal Ca2+ is
      cytotoxic. Using fluorescence microscopy, we demonstrate that extracellular Ca2+
      at the site of plasmalemmal transection is necessary to form a plasmalemmal
      barrier, and that other divalent ions (Ba2+, Mg2+) do not play a major role. We
      also show that extracellular Ca2+, rather than injury per se, initiates the
      formation of a plasmalemmal barrier and that a transient increase in somal
      [Ca2+]i significantly decreases the percentage of cells that survive neurite
      transection. Furthermore, we show that the increased somal [Ca2+]i and decreased
      cell survival following proximal transections are not due to less frequent or
      slower plasmalemmal sealing or Ca2+ entry through plasmalemmal Na+ and Ca2+
      channels. Rather, the increased somal [Ca2+]i and lethality of proximal neurite
      injuries may be due to the decreased path length/increased diameter for Ca2+
      entering the transection site to reach the soma. A ryanodine block of Ca2+
      release from internal stores before transection has no effect on cell survival;
      however, a ryanodine- or thapsigargin-induced buildup of somal [Ca2+]i before
      transection markedly reduces cell survival, suggesting a minor involvement of
      Ca2+-induced release from internal stores. Finally, we show that cell survival
      following proximal injuries can be enhanced by increasing intracellular Ca2+
      buffering capacity with BAPTA to prevent the increase in somal [Ca2+]i.

PMID- 15266647
TI  - GABAB receptor expression and function in olfactory receptor neuron axon growth.
AB  - Neurotransmitters have been implicated in regulating growth cone motility and
      guidance in the developing nervous system. Anatomical and electrophysiological
      studies show the presence of functional GABAB receptors on adult olfactory
      receptor neuron (ORN) nerve terminals. Using antisera against the GABAB R1a/b
      receptor isoforms we show that developing mouse olfactory receptor neurons
      express GABAB receptors from embryonic day 14 through to adulthood. GABAB
      receptors are present on axon growth cones from both dissociated ORNs and
      olfactory epithelial explants. Neurons in the olfactory bulb begin to express
      glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, from E16
      through to adulthood. When dissociated ORNs were cultured in the presence of the
      GABAB receptor agonists, baclofen or SKF97541, neurite outgrowth was
      significantly reduced. Concurrent treatment of the neurons with baclofen and the
      GABAB receptor antagonist CGP54626 prevented the inhibitory effects of baclofen
      on ORN neurite outgrowth. These results show that growing ORN axons express GABAB
      receptors and are sensitive to the effects of GABAB receptor activation. Thus,
      ORNs in vivo may detect GABA release from juxtaglomerular cells as they enter the
      glomerular layer and use this as a signal to limit their outgrowth and find
      synaptic targets in regeneration and development.

PMID- 15266648
TI  - Developmental shift in bidirectional functions of taurine-sensitive chloride
      channels during cortical circuit formation in postnatal mouse brain.
AB  - Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in the
      developing mammalian cerebral cortex, however, few studies have reported its
      neurobiological functions during development. In this study, by means of whole
      cell patch-clamp recordings, we examined the effects of taurine on chloride
      channel receptors in neocortical neurons from early to late postnatal stages,
      which cover a critical period in cortical circuit formation. We show here that
      taurine activates chloride channels in cortical neurons throughout the postnatal
      stages examined (from postnatal day 2 to day 36). The physiological effects of
      taurine changed from excitatory to inhibitory due to variations in the
      intracellular Cl- concentration during development. An antagonist blocking
      analysis also demonstrated a developmental shift in the receptor target of
      taurine, from glycine receptors to GABAA receptors. Taken together, these results
      may reflect genetically programmed, bidirectional functions of taurine. At the
      early developmental stage, taurine acting on glycine receptors would serve to
      promote cortical circuit formation. As cortical circuit has to be regulated in
      the later stages, taurine would serve as a safeguard against hyperexcitable
      circuit.

PMID- 15266649
TI  - Nitric oxide modulates local reflexes of the tailfan of the crayfish.
AB  - Electrical stimulation of sensory neurons that innervate receptors on the tailfan
      of crayfish evokes a reflex response of motor neurons that produce movements of
      the blades of the tailfan, the uropods. We analyzed the modulatory effects of
      nitric oxide (NO) on the spike frequency of the reflex response. Bath application
      of L-arginine and SNAP, which elevate endogenous and exogenous NO levels,
      increased the frequency of the evoked response, whereas the application of L-NAME
      and PTIO, which reduce NO levels, decreased the frequency of the response. To
      determine through what pathway and target NO exerted these effects we bath
      applied ODQ, an inhibitor of soluble guanylyl cyclase (sGC), which decreased the
      frequency of response, and 8-br-cGMP, which increased the spike frequency of
      response. To provide further evidence that NO acts via sGC, we elevated NO levels
      with L-arginine while simultaneously inhibiting sGC with ODQ. This application
      reduced the response to control levels, indicating that NO in the terminal
      ganglion of crayfish acts via sGC to modulate cGMP levels, which in turn regulate
      the responses of the uropod motor neurons.

PMID- 15266650
TI  - Myosin Va and kinesin II motor proteins are concentrated in ribosomal domains
      (periaxoplasmic ribosomal plaques) of myelinated axons.
AB  - Periaxoplasmic ribosomal plaques (PARPs) are discrete ribosome-containing domains
      distributed intermittently along the periphery of axoplasm in myelinated fibers.
      Thus, they are structural formations in which translational machinery is
      spatially organized to serve as centers of protein synthesis for local metabolic
      requirements and perhaps repair as well. Because of evidence that RNA is
      transported to putative PARP domains, involving both microtubule- and actin-based
      mechanisms, it was of interest to investigate whether cytoskeletal motor proteins
      exhibit a nonrandom localization within PARP domains. Axoplasm, from large
      Mauthner fibers and rat or rabbit spinal ventral nerve root fibers, removed from
      the myelin sheath in the form of an "axoplasmic whole-mount" was used for this
      analysis. PARP domains were identified either by specific immunofluorescence of
      rRNA, ribosomal P antigen, or by nonspecific RNA fluorescence using RNA binding
      dyes YOYO-1 or POPO-1. A polyclonal antibody (pAb) against the motor domain of
      myosin Va showed prominent nonrandom immunofluorescence labeling in PARP domains.
      Similarly, monoclonal antibodies (mAb) against kinesin KIF3A and a pan-specific
      antikinesin (mAb IBII) also showed a preponderant immunofluorescence in PARP
      domains. On the other hand, H2, a mAb antikinesin KIF5A, exhibited only random
      immunofluorescence labeling in axoplasm, as was also the case with pAb antidynein
      heavy chain immunofluorescence. Several possible explanations for these findings
      are considered, primary among which is targeted trafficking of translational
      machinery that results in local accumulation of motor proteins. Additional
      possibilities are trafficking functions intrinsic to the domain, and/or functions
      that govern dynamic organizational properties of PARPs.

PMID- 15266651
TI  - Functional restoration of acoustic units and adult-generated neurons after
      hypothalamic lesion.
AB  - The hypothalamus of the adult ring dove contains acoustic units that respond to
      species-specific coo vocalization. Loss of nest coo leads to unsuccessful
      breeding. However, the recovery of nest coo in some doves suggests that these
      units are capable of self-renewal. We have previously shown that lesioning the
      hypothalamus generates the addition of new neurons at the lesioned area. In this
      study, we sought to determine whether lesion-induced new neurons are involved in
      the recovery of coo-responsive units. We systematically recorded electrical
      activity in the ventromedial nucleus (VMN) of the hypothalamus, before and after
      lesion, for varying periods up to 3 months. Recordings were made when the birds
      were at rest (spontaneous discharge) and when the birds were exposed to acoustic
      stimulations (evoked discharge). Concurrently, the lesioned area was monitored
      for changes in cell types by using bromodeoxyuridine (BrdU) to label newly
      divided cells and NeuN to identify mature neurons. For 1 month after lesion,
      there was no sign of electrical activity, and only BrdU-labeled cells were
      present. When the first electrical activity occurred, it displayed abnormal
      spontaneous bursting patterns. The mature discharge patterns (both spontaneous
      and evoked) occurred after detection of BrdU+/NeuN+ double-labeled cells 2-3
      months postlesion and were similar to those found in intact and sham-lesioned
      birds. Double-labeled cells bore morphologic characteristics of a neuron and were
      confirmed with z-stack analysis using confocal laser scanning microscopy.
      Moreover, double-labeled cells were not stained for glial fibrillary acidic
      protein (GFAP), suggesting that they were neurons. The number of coo-responsive
      units was significantly correlated with that of BrdU+/NeuN+ cells. Furthermore,
      the marker for recording sites revealed that coo-responsive units were
      colocalized with BrdU+/NeuN+ cells. Taken together, the evidence strongly
      suggests that lesion-induced addition of new neurons promotes the functional
      recovery of the adult hypothalamus.

PMID- 15266652
TI  - Age-associated synapse elimination in mouse parasympathetic ganglia.
AB  - Little is known about the effects of aging on synapses in the mammalian nervous
      system. We examined the innervation of individual mouse submandibular ganglion
      (SMG) neurons for evidence of age-related changes in synapse efficacy and number.
      For approximately 85% of adult life expectancy (30 months) the efficacy of
      synaptic transmission, as determined by excitatory postsynaptic potential (EPSP)
      amplitudes, remains constant. Similarly, the number of synapses contacting
      individual SMG neurons is also unchanged. After 30 months of age, however, some
      neurons (23%) dramatically lose synaptic input exhibiting both smaller EPSP
      amplitude and fewer synaptic boutons. Attenuation of both the amplitude and
      frequency of miniature EPSPs was also observed in neurons from aged animals.
      Electron micrographs revealed that, although there were many vesicle-laden
      preganglionic axonal processes in the vicinity of the postsynaptic membrane, the
      number of synaptic contacts was significantly lower in old animals. These results
      demonstrate primary, age-associated synapse elimination with functional
      consequences that cannot be explained by pre- or postsynaptic cell death.

PMID- 15266653
TI  - Properties of Xenopus Kv1.10 channels expressed in HEK293 cells.
AB  - Voltage-gated K+ channels play important roles in shaping the characteristics of
      action potentials and electrical activity. In a previous study, we isolated cDNAs
      encoding several distinct K+ channel isoforms, including a novel isoform
      (XKv1.10) expressed in Xenopus laevis spinal cord neurons and myocytes. Here, we
      report the biophysical characterization of XKv1.10 expressed in transiently
      transfected HEK293 cells. Whole cell patch clamp recordings revealed a voltage
      gated, rapidly activating and inactivating K+ current. Interestingly, the rate of
      inactivation of XKv1.10 channels showed apparent voltage dependence, with time
      constants between 77.7-213.3 ms. The predicted protein sequence of XKv1.10 does
      not appear to encode an N-terminal inactivating "ball and chain" domain, and
      instead these channels may inactivate via a C/P-type mechanism. Consistent with
      this, either increasing the external concentration of K+ or external application
      of tetraethylammonium caused a decrease in the rate of inactivation.
      Pharmacologically, XKv1.10 K+ channels were sensitive to 4-aminopyridine and
      tetraethylammonium with apparent IC50 values of 68.5 microM and 17.1 mM,
      respectively. When simulated action potentials were used as a voltage command,
      XKv1.10 was similar to XKv1.4 in that it carried more repolarizing current during
      the action potential than XKv1.2. However, while XKv1.4 was active during the
      interspike interval, XKv1.10 and XKv1.2 were not. Overall, the data suggest that
      XKv1.10 channels make a unique contribution to the developmental maturation of
      electrical signaling in Xenopus laevis.

PMID- 15266654
TI  - Chronic stress alters dendritic morphology in rat medial prefrontal cortex.
AB  - Chronic stress produces deficits in cognition accompanied by alterations in
      neural chemistry and morphology. Medial prefrontal cortex is a target for
      glucocorticoids involved in the stress response. We have previously demonstrated
      that 3 weeks of daily corticosterone injections result in dendritic
      reorganization in pyramidal neurons in layer II-III of medial prefrontal cortex.
      To determine if similar morphological changes occur in response to chronic
      stress, we assessed the effects of daily restraint stress on dendritic morphology
      in medial prefrontal cortex. Male rats were exposed to either 3 h of restraint
      stress daily for 3 weeks or left unhandled except for weighing during this
      period. On the last day of restraint, animals were overdosed and brains were
      stained using a Golgi-Cox procedure. Pyramidal neurons in lamina II-III of medial
      prefrontal cortex were drawn in three dimensions, and the morphology of apical
      and basilar arbors was quantified. Sholl analyses demonstrated a significant
      alteration of apical dendrites in stressed animals: overall, the number and
      length of apical dendritic branches was reduced by 18 and 32%, respectively. The
      reduction in apical dendritic arbor was restricted to distal and higher-order
      branches, and may reflect atrophy of terminal branches: terminal branch number
      and length were reduced by 19 and 35%. On the other hand, basilar dendrites were
      not affected. This pattern of dendritic reorganization is similar to that seen
      after daily corticosterone injections. This reorganization likely reflects
      functional changes in prefrontal cortex and may contribute to stress-induced
      changes in cognition.

PMID- 15266655
TI  - Repetitive exposures to nicotine induce a hyper-responsiveness via the
      cAMP/PKA/CREB signal pathway in Drosophila.
AB  - Nicotine, in addition to acute effects, has long-lasting effects on mammalian
      behaviors, such as those leading to addiction. Here we present genetic and
      pharmacological evidence in Drosophila suggesting that repetitive exposures to
      nicotine induce a hyper-responsiveness through synthesis of new protein(s) via
      CREB-mediated gene transcription. Single exposure to volatilized nicotine dose
      dependently inhibited the startle-induced climbing response. Compared with this
      effect of nicotine in wild-type flies, it was stronger in dunce, which has
      defective phosphodiesterase, and in wild-type flies treated with a
      phosphodiesterase inhibitor, whereas it was weaker in DC0, which has defective
      protein kinase A (PKA), and in wild-type flies treated with a PKA blocker. Thus,
      the effect of nicotine is enhanced by a mechanism involving the cAMP/PKA cascade.
      However, in wild-type flies, an increase in head cAMP was not detected within 2
      min after single exposure to nicotine, during which the nicotine effect on the
      behavior was maximal. In wild-type flies, after repetitive exposures to nicotine,
      the nicotine effect was significantly enhanced and the head cAMP was elevated.
      The responsiveness to nicotine at second exposure increased with a 4 h interval
      but not with a 2 h interval, suggesting that the observed hyper-responsiveness
      was not due to accumulation of residual nicotine. Both enhancement of the
      nicotine effect and elevation of cAMP during repetitive exposures to nicotine
      were blocked by a protein synthesis inhibitor. Induction of a dominant negative
      CREB transgene also blocked the enhancement, suggesting that CREB-mediated gene
      transcription is required for the hyper-responsiveness.

PMID- 15266656
TI  - Deficits and recovery of body stabilization during acrobatic locomotion after
      focal lesion to the somatosensory cortex: a kinematic analysis combined with
      cortical mapping.
AB  - We used a kinematic analysis for assessing locomotor impairments and evaluating
      the time course of recovery after focal injury to the forepaw area of the primary
      somatosensory cortex (SI) in rats. The animals were trained to traverse a beam
      that was rotated at various speeds. Changes in orientation of the body and
      independent movement of the anterior and posterior parts of the body were
      reconstructed using a 3D motion analysis. In addition, we used
      electrophysiological cortical mapping to search for neurophysiological changes
      within the spared cortical zones surrounding the lesion. Neuronal recordings were
      performed in the same animals prior to and 3 weeks after the lesion induction.
      Our findings show that a focal lesion that destroyed about 60% of the forepaw
      representational zone was sufficient to cause conspicuous impairments in the
      rats' ability to produce adequate motor adjustments to compensate for the lateral
      shift of the beam and to avoid falling. The main deficits were reflected in a
      lack of appropriate coordination between the anterior and posterior parts of the
      body and an inability to maintain a regular gait during locomotion. Skilled
      locomotion was fully recovered within a 2-3 week period. Functional recovery
      cannot be ascribed to a restitution of the lost sensory representations. A
      permanent decrease of forepaw representation was recorded despite the re
      emergence of restricted representational sectors in the peri-lesion zone. We
      suggest that alterations may have occurred in other cortical and subcortical
      areas interconnected with the injured area. It is also conceivable that the
      functional recovery involved an increased reliance on all the available sources
      of sensorimotor regulation as well as the use of behavioral strategies.

PMID- 15266659
TI  - Bibliography. Current world literature. Infectious arthritis and immune
      dysfunction.

PMID- 15266658
TI  - Open psychiatric services in interwar France.
AB  - The open psychiatric service established in Paris by Edoward Toulouse was meant
      to provide early, active psychiatric treatment to mildly afflicted individuals
      without subjecting them to legal commitment. Psychiatric reformers also hoped
      that the service would help to raise the status of psychiatry by typing their
      specialty's fate to laboratory science and hospital medicine. This article traces
      the genesis of open psychiatric services in interwar France and survey the
      debates they engendered within the French psychiatric community. It highlights
      the role of World War I in the implementation of open services and in the
      creation of a pool of patients who required assistance.

PMID- 15266660
TI  - Bibliography. Current world literature. Metabolic bone disease.

PMID- 15266661
TI  - Cardiomyopathy in muscular dystrophy workshop. 28-30 September 2003, Tucson,
      Arizona.

PMID- 15266662
TI  - The beer ration in Victorian asylums.
AB  - Routine distribution of alcoholic beverages to mental hospital patients would be
      a fanciful prospect today, yet in the formative decades of lunatic asylums, beer
      was standard issue. A staple item in the supposedly healthy Victorian asylum
      diet, beer also served as inducement for patient labour. Around the mid-1880s,
      this commodity was abolished throughout Britain's mental institutions. This paper
      explores the factors that combined to condemn the beer barrel to asylum history,
      and, in particular, how this small comfort for immates fell foul of the
      medicalization of the asylum and of the professional project of psychiatry.

PMID- 15266663
TI  - Animal use in higher education in the SEE (South Eastern Europe) region.
AB  - In the SSE region the alternatives to animal use in higher education, which can
      decrease or completely exclude animal use for dissection and vivisection
      purposes, are still not well known. A survey of the current situation at
      universities and other educational institutions, including primary and secondary
      schools, shows that alternatives will remain under the shadow of unnecessary
      dissections and animal experiments performed on numerous animal species for a
      long time to come.

PMID- 15266664
TI  - Manganese superoxide dismutase gene polymorphisms in psoriatic arthritis.
AB  - The purpose of the present study is to investigate the role of manganese
      superoxide dismutase (MnSOD) gene polymorphisms in the susceptibility to
      psoriatic arthritis. MnSOD gene polymorphisms were determined by polymerase chain
      reaction/restriction fragment length polymorphisms method in fifty-two patients
      with psoriatic arthritis and 90 healthy controls.The genotype frequency of MnSOD
      1183C/T was significantly higher in patients with psoriatic arthritis than in
      controls. In contrast, the frequency of MnSOD 1183T/T was significantly decreased
      in patients with psoriatic arthritis. The phenotype frequency of MnSOD 1183C was
      significantly increased in patients with psoriatics arthritis in comparison to
      healthy controls.Therefore, MnSOD 1183C polymorphisms may be a precipitating
      factor for the development of psoriatic arthritis.

PMID- 15266665
TI  - Chronotherapy of high-dose active Vitamin D(3): is evening dosing preferable?
AB  - Oral Vitamin D(3) is usually administered to children with chronic renal failure
      in the morning. Is there enough evidence that evening dosing is more beneficial
      with respect to suppression of parathyroid hormone and reduction of side effects
      such as hypercalcemia?

PMID- 15266666
TI  - Age at menarche and associated factors.

PMID- 15266668
TI  - Contralateral medial rectus muscle recession in patients with Duane syndrome.

PMID- 15266667
TI  - Discovery of ovarian cancer biomarkers in serum using NanoLC electrospray
      ionization TOF and FT-ICR mass spectrometry.
AB  - Treatment of cancer patients is greatly facilitated by detection of the cancer
      prior to metastasis. One of the obstacles to early cancer detection is the lack
      of availability of biomarkers with sufficient specificity. With modem
      differential proteomic techniques, the potential exists to identify high
      specificity cancer biomarkers. We have delineated a set of protocols for the
      isolation and identification of serum biomarkers for ovarian cancer that exist in
      the low molecular weight serum fraction. After isolation of the low molecular
      weight fraction by ultrafiltration, the potential biomarkers are separated by
      reversed phase nano liquid chromatography. Detection via TOF or FT-ICR yields a
      data set for each sample. We compared stage III/IV ovarian cancer serum with
      postmenopausal age-matched controls. Using bioinformatics tools developed at
      Mayo, we normalized each sample for intensity and chromatographic alignment.
      Normalized data sets are subsequently compared and potential biomarkers
      identified. Several candidate biomarkers were found. One of these contains the
      sequence of fibrinopeptide-A known to be elevated in many types of cancer
      including ovarian cancer. The protocols utilized will be examined and would be
      applicable to a wide variety of cancers or disease states.

PMID- 15266670
TI  - Lavinia Ness.

PMID- 15266669
TI  - Spatial analysis of body mass index and smoking behavior among WISEWOMAN
      participants.
AB  - BACKGROUND: The WISEWOMAN program focuses on reducing cardiovascular disease
      (CVD) risk factors by providing screening and lifestyle interventions for many
      low-income and uninsured women. To provide the most effective interventions
      possible, it is important to understand the characteristics of WISEWOMAN
      participants and their communities. METHODS: We used baseline data collected for
      WISEWOMAN participants from five states (Connecticut, Michigan, Nebraska, North
      Carolina, and South Dakota) who had enrolled in WISEWOMAN between January 2001
      and December 2002 in order to examine body mass index (BMI) and smoking behavior
      for evidence of spatial clustering. We then examined whether neighborhood
      characteristics in clusters of high-risk factors differed from neighborhood
      characteristics in other locations. RESULTS: Six percent of the WISEWOMAN
      participants lived in ZIP codes with high-BMI clusters, and 4% lived in ZIP codes
      with high-smoking clusters. High-BMI and high-smoking clusters occurred, however,
      in different locations from each other. The high-BMI-clustered ZIP codes were, on
      average, located in more disadvantaged areas. Most of the differences between the
      high-smoking-clustered ZIP codes and the remaining ZIP codes were not
      statistically significant. CONCLUSIONS: Our analysis revealed spatial clustering
      in CVD risk factors among WISE-WOMAN participants. We also found evidence of a
      correlation between high-BMI clusters and low socioeconomic status of the
      surrounding community. A more in-depth analysis of the relationship between risk
      factors (e.g., BMI) and community characteristics in clustered locations will
      provide further information concerning the role of the community in affecting
      individual behavior and should allow for tailoring interventions to reduce these
      risk factors more effectively.

PMID- 15266671
TI  - 2004 Frechette Awards.

PMID- 15266672
TI  - Class inequality and meritocracy: a critique of Saunders and an alternative
      analysis.
AB  - Saunders' recent work claiming that contemporary British society is to a large
      extent 'meritocratic' is criticized on conceptual and technical grounds. A
      reanalysis of the National Child Development Study data-set, used by Saunders, is
      presented. This reveals that while merit, defined in terms of ability and effort,
      does play a part in determining individuals' class destinations, the effect of
      class origins remains strong. Children of less advantaged class origins need to
      show substantially more merit than children from more advantaged origins in order
      to gain similar class positions. These differences in findings to some extent
      arise from the correction of biases introduced by Saunders; but there are also
      features of his own results, consistent with those reported in the reanalysis,
      which he appears not to have fully appreciated.

PMID- 15266673
TI  - Social mobility and personal satisfaction: evidence from ten countries.
AB  - This paper examines survey data relating class mobility to satisfaction and
      dissatisfaction with seven different domains of everyday life among nationally
      representative samples of men and women living in ten industrialized nations. The
      evidence is set against competing pessimistic and optimistic accounts of the
      mobility experience found in earlier literature. Results show that individuals
      who move from working-class origins to middle-class destinations are no more
      likely to be systematically satisfied or dissatisfied with life than are the
      socially immobile or even those downwardly mobile from advantaged backgrounds
      into the working class. Indeed, in all nations, the overall association between
      class experience and satisfaction with life is both weak and uneven across the
      different life-domains. The study also serves to illustrate an important
      principle of research methodology more generally.

PMID- 15266674
TI  - Is there an underclass in Britain?
AB  - This paper sets out to define the underclass and then test the predictions of
      three competing theories in the underclass debate. Using the National Child
      Development Study for the analysis it is found that an 'underclass' suffering
      from a lack of qualifications, low cognitive ability and chronic joblessness
      exists. The validity of making a distinction between the working class and an
      'underclass' has often been questioned both because of the dubious history of
      such a distinction and because it is not believed that such a distinction is
      empirically true. The results in this paper contradict this assertion by finding
      the underclass to be distinctive from the working class in terms of patterns of
      family formation, work commitment and political allegiance. The distinct
      attitudes of the underclass, when coupled with evidence of inter- and intra
      generational stability of membership, provide early evidence that a new social
      class, the underclass, may now exist in Britain.

PMID- 15266675
TI  - Capitalism, money and banking: a critique of recent historical sociology.
AB  - A conception of money as a 'neutral veil' masking a 'real' economy was adopted by
      orthodox economic theory after the Methodenstreit, and is also to be found, in a
      different form, in Marxian political economy. Both derive from an erroneous
      functionalist and anachronistic 'commodity' theory of money which, as Post
      Keynesian economists argue, cannot explain the distinctive form of capitalist
      credit-money. Orthodox economic theory and classic Marxism have tacitly informed
      and flawed historical sociology's understanding of money's role in capitalist
      development. Mann and Runciman, for example, consider the 'economy' exclusively
      in terms of the social relations of production and imply that money is
      epiphenomenal and is to be explained as a response to the needs of the 'real'
      economy. They do not recognize the structural specificity of capitalist money and
      banking nor its importance. An alternative account of the autonomous historical
      conditions of existence of the specifically capitalist form of bank and state
      credit-money and its role in capitalist development is outlined.

PMID- 15266676
TI  - Gender and income in pharmacy: human capital and gender stratification theories
      revisited.
AB  - This is a case study of gender and earnings in pharmacy--a profession
      characterized by its rapid recruitment of female practitioners. We try to account
      for disparities in earnings between male and female pharmacists in Ontario with
      the aid of human capital theory and gender stratification theory. Data is drawn
      from a random sample of 463 Ontario pharmacists. We find a consistent sex gap in
      earnings regardless of occupational level of practitioners (i.e. owner, manager
      or employee) and net of such factors as hours worked, commitment to work, hours
      devoted to childcare, absences from the labour market, and years since
      graduation. Instead, the main reason why women in pharmacy earn less than males
      is because they remain employees throughout their careers. However, we are less
      successful at identifying the additional factors responsible for the depressed
      earnings of female practitioners. We discuss our findings in light of the claims
      of gender stratification and human capital theory.

PMID- 15266677
TI  - The new regulatory state: the social powers of the European Union.
AB  - The understanding of the European Union poses a challenge for Sociology and its
      traditional conceptions of the state. In particular, the impact of the social
      dimension has been underestimated and undervalued. This paper explores the
      implications of the developing social dimension of the European Union for
      European social relations in the context of globalization which allegedly reduces
      the power of states to act effectively in the social realm. It argues for a
      broader conceptualization of the social dimension and for a new conception of the
      regulatory state. It argues that the significance of a politico-legal project
      social justice. It concludes with a re-consideration of the powers of the state
      in an era of globalization

PMID- 15266678
TI  - Modernity: a non-European conceptualization.
AB  - In the light of insights drawn from historical sociology and Parsons' theory of
      differentiation/modernization, an attempt is made to conceptualize modernity in
      such a way as to avoid both eurocentrism and the total rejection of the concept
      by those who view it as an ideological means for the further advancement of
      western cultural imperialism.

PMID- 15266679
TI  - Criteria to determine disability related to multiple sclerosis.

PMID- 15266680
TI  - Use of the up-and-down acute toxicity test procedure to generate LC50 data for
      fish.

PMID- 15266681
TI  - Influence of temperature on the mortality and sensitivity of Corophium orientale.

PMID- 15266682
TI  - Ambon damsel (Pomacentrus amboinensis) as a bioindicator organism for the Great
      Barrier Reef: responses to chlorpyrifos.

PMID- 15266684
TI  - Toxicity identification evaluation of organic pollutants based on solid-phase
      micro-extraction and gas chromatography/mass spectrometry.

PMID- 15266683
TI  - Delayed fluorescence of Lemna minor: a biomarker of the effects of copper,
      cadmium, and zinc.

PMID- 15266685
TI  - Identification of the phthalate-degrading bacteria isolated from phthalate
      contaminated soil and characterization of their phthalate substrate specificity.

PMID- 15266686
TI  - Metals in airborne particulate matter in downtown Rio de Janeiro, Brazil.

PMID- 15266687
TI  - Composition and source of unknown organic pollutants in atmospheric particulates
      of the Xigu District, Lanzhou, People's Republic of China.

PMID- 15266688
TI  - Comparison of selected toxic elements in cow serum and milk samples from
      industrial and rural regions.

PMID- 15266689
TI  - Primary investigation of heavy metal contamination status in molluscs collected
      from Chinese coastal sites.

PMID- 15266690
TI  - Butyltin compounds distribution in the coastal waters of Bohai Bay, People's
      Republic of China.

PMID- 15266691
TI  - Accumulation features of organochlorine pesticides residues in soils around
      Beijing Guanting reservoir.

PMID- 15266692
TI  - Trifluralin residues in runoff and infiltration water from tomato production.

PMID- 15266693
TI  - Estimation of residues of profenofos in/on tomato, Lycopersicon esculentum Mill.

PMID- 15266694
TI  - Fluvalinate residues in honey and beeswax after different colony treatments.

PMID- 15266695
TI  - Arsenic uptake by reptile flexible-shelled eggs from contaminated nest substrates
      and toxic effect on embryos.

PMID- 15266696
TI  - Selection of mustard oilseed rape (Brassica juncea L.) for phytoremediation of
      cadmium contaminated soil.

PMID- 15266697
TI  - Photolysis of octachloronaphthalene in hexane.

PMID- 15266698
TI  - Toxicity of benzene, toluene, ethylbenzene, and xylene (BTEX) mixtures to Sorghum
      bicolor and Cucumis sativus.

PMID- 15266699
TI  - Effects of nitrite on bullfrog (Rana catesbeiana) tadpoles from central Ohio,
      USA.

PMID- 15266700
TI  - Morphoanatomical response of two varieties of Brassica juncea (L.) Czern. grown
      on tannery sludge amended soil.

PMID- 15266701
TI  - Sublethal behavioral effects of the water accommodated fractions of crude oil to
      gastropod molluscs.

PMID- 15266702
TI  - Effects of aquatic herbicides on primary productivity of phytoplankton in the
      laboratory.

PMID- 15266703
TI  - Cadmium toxicity to Ceratophyllum demersum L.: morphological symptoms, membrane
      damage, and ion leakage.

PMID- 15266705
TI  - Toxic effects of unionized ammonia on survival and feeding activity of the
      freshwater amphipod Eulimnogammarus toletanus (Gammaridae, Crustacea).

PMID- 15266704
TI  - Multiple metal resistance in the ciliate protozoan, Vorticella microstoma,
      isolated from industrial effluents and its potential in bioremediation of toxic
      wastes.

PMID- 15266706
TI  - Effect of river humic acid on 1-aminopyrene ecotoxicity in a dynamic solar
      photolysis process.

PMID- 15266707
TI  - Relationship of chemical-based effluent regulations of Korea to aquatic
      toxicities to microbes, macroinvertebrates, and fish.

PMID- 15266708
TI  - Effect of water pH on copper toxicity in the neotropical fish, Prochilodus scrofa
      (Prochilodondidae).

PMID- 15266709
TI  - Effects of cadmium on the survival of three life-stages of the freshwater
      pulmonate Lymnaea stagnalis (Mollusca: Gastropoda).

PMID- 15266710
TI  - A history of the Federation of European Societies of Plant Physiology FESPP since
      its foundation in 1978--including notes on events preceding the foundation and
      following re-naming as the Federation of European Societies of Plant Biology
      (FESPB) in 2002.
AB  - After several years of close contacts and extensive discussion between various
      plant physiologists of different European countries, the Federation of European
      Societies of Plant Physiology (FESPP) was established in 1978 in Edinburgh. The
      aim of the FESPP was and remains to promote up-to-date plant physiology research
      in all European countries and to stimulate scientific cooperation and the
      exchange of scientists between the different member societies by organizing
      congresses and workshops as well as editing four (recently five) Federation
      affiliated journals. The short History of FESPP presented here covers the
      preparatory years of the 1970s that led to its actual foundation in 1978, and
      then its further development up to and following the Federation's reconstitution
      in 2002 as the Federation of European Societies of Plant Biology (FESPB).

PMID- 15266711
TI  - A new type of thermoluminometer: a highly sensitive tool in applied
      photosynthesis research and plant stress physiology.
AB  - Here we describe a newly developed thermoluminescence measuring device that
      employs flash excitation, peltier heating, and light detection by channel
      photomultipliers (CPM). The new thermoluminometer is equipped with four sample
      holders for simultaneous measurements of thermoinduced light emission in the
      temperature range from -20 degrees C to +180 degrees C. It allows one to measure
      leaf samples, chloroplasts, thylakoids, algae, or even bioorganic material
      lacking chlorophyll by means of naturally induced or artificially applied
      chemilumigenic probes. The temperature range of the thermoluminometer allows one
      to analyse the thermoinduced radical pair recombination of photosystem II in the
      lower temperature region as well as chemiluminescence from lipid peroxidation in
      the higher temperature region. Hence, plant material can be assessed concerning
      both its photosynthetic and its oxidative stress status. Since the device is
      equipped with four sample holders and four CPM channels for simultaneous
      detection of thermoinduced light emission, it facilitates a high throughput.
      Therefore, the new device is interesting, not only in ecophysiology, but also in
      the field of plant breeding, as it can be used to study the stress tolerance of
      various cultivars of cultural crop plants.

PMID- 15266712
TI  - Differential in vitro development of inflorescences in long and short day Lemna
      spp.: involvement of ethylene and polyamines.
AB  - In vitro-development of Lemna inflorescences on minimal medium is known to differ
      in long day (LDP) and short day (SDP) plants (Z. Pfl, physiol. 77, 395). In LDP
      pistil growth predominates, while in SDP stamen growth predominates. This
      indicates that LDP and SDP inflorescences differ in endogenous hormones and
      depend for a balanced male-female development on different plant-supplied factors
      (Z. Pfl. physiol. 80, 283 and 298). Here inflorescences of the LDP L. gibba and
      the SDP L. aequinoctialis were tested for differences in ethylene-polyamine (PA)
      relations, as ethylene and PAs are inversely related (shared precursor, mutual
      inhibition of synthesis), and exogenous ethylene has been shown previously to
      restore male-female balance in SDP inflorescences (Z. Pfl. physiol. 80, 283).
      Promotion of pistil or stamen growth indicates a predominance of ethylene and PAs
      in LDP and SDP, respectively. Hence, in LDP, exogenous PAs and inhibitors of
      ethylene synthesis, and in SDP, an inhibitor of PA-synthesis, were applied to
      restore the male-female balance in vitro. In L. aequinoctialis (SDP), application
      of methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of spermidine (SD)
      synthesis, resulted in near normal development via stamen inhibition and/or
      pistil promotion. In L. gibba (LDP), ethylene inhibition was effective,
      especially by aminoethoxyvinylglycine (AVG), which reduced pistil growth. Effects
      of alpha-aminooxyacetic acid (AOA) were less clear. Putrescine (PUT) promoted
      stamen growth under certain circumstances, perhaps acting as a precursor for the
      more active SD. SD effects were concentration-dependent for pistil and stamen.
      Most importantly, increases in SD turned pistil promotion into inhibition and
      almost normalised floral development. Spermine (SM) enhanced stamen growth.
      Results are conclusive that PA-ethylene relationships are involved in
      inflorescence development in a contrasting manner in LDP and SDP. It is apparent
      that in whole plants the LDP supplies the inflorescences with factors inhibiting
      ethylene and/or stimulating PA-synthesis. In SDP the converse is true.

PMID- 15266713
TI  - Synthesis of phytochelatins and modulation of antioxidants in response to cadmium
      stress in Cuscuta reflexa--an angiospermic parasite.
AB  - Effect of cadmium on growth, antioxidative enzymes namely catalase, peroxidase,
      glutathione reductase, level of glutathione and phytochelatin synthesis was
      investigated in callus and seedlings of Cuscuta reflexa. A time, concentration
      and tissue dependent response of Cd was observed. Cd inhibited the growth of
      callus and seedlings by 50% at 300 and 500 micromol/L concentrations,
      respectively. Shorter exposure of low concentration of Cd led to augmentation of
      antioxidant activity, both in callus and seedlings, while longer exposure and
      high concentration of Cd led to a concentration dependent decrease in callus.
      Analysis of phytochelatin (PC) synthesis in callus and seedlings of C. reflexa
      revealed both quantitative and qualitative changes. Cd at low concentrations led
      to synthesis of predominantly PC4, while at higher concentrations, PC3 was the
      major form being synthesized. Amelioration of antioxidative systems of C. reflexa
      in response to Cd stress might be playing a protective role, alleviating the
      damaging effects of ROS, generated during Cd stress. Concomitantly, chelation and
      sequestering of toxic Cd ions in this parasite was mediated by synthesis of PC.
      The response to Cd stress shown by this holoparasitic plant was found to be
      similar to those of non-parasitic plants (hosts).

PMID- 15266714
TI  - Variations in water status, gas exchange, and growth in Rosmarinus officinalis
      plants infected with Glomus deserticola under drought conditions.
AB  - The influence of the arbuscular mycorrhizal fungus Glomus deserticola on the
      water relations, gas exchange parameters, and vegetative growth of Rosmarinus
      officinalis plants under water stress was studied. Plants were grown with and
      without the mycorrhizal fungus under glasshouse conditions and subjected to water
      stress by withholding irrigation water for 14 days. Along the experimental
      period, a significant effect of the fungus on the plant growth was observed, and
      under water stress, mycorrhizal plants showed an increase in aerial and root
      biomass compared to non-mycorrhizal plants. The decrease in the soil water
      potential generated a decrease in leaf water potential (psi(l)) and stem water
      potential (psi(x)) of mycorrhizal and non-mycorrhizal plants, with this decrease
      being lower in mycorrhizal water-stressed plants. Mycorrhization also had
      positive effects on the root hydraulic conductivity (Lp) of water stressed
      plants. Furthermore, mycorrhizal-stressed plants showed a more important decrease
      in osmotic potential at full turgor (psi(os)) than did non-mycorrhizal-stressed
      plants, indicating the capacity of osmotic adjustment. Mycorrhizal infection also
      improved photosynthetic activity (Pn) and stomatal conductance (g(s)) in plants
      under water stress compared to the non-mycorrhizal-stressed plants. A similar
      behaviour was observed in the photochemical efficiency of PSII (Fv/Fm) with this
      parameter being lower in non-mycorrhizal plants than in mycorrhizal plants under
      water stress conditions. In the same way, under water restriction, mycorrhizal
      plants showed higher values of chlorophyll content than did non-mycorrhizal
      plants. Thus, the results obtained indicated that the mycorrhizal symbiosis had a
      beneficial effect on the water status and growth of Rosmarinus officinalis plants
      under water-stress conditions.

PMID- 15266715
TI  - Changes in soluble carbohydrates and related enzymes induced by low temperature
      during early developmental stages of quinoa (Chenopodium quinoa) seedlings.
AB  - Low temperature represents one of the principal limitations in species
      distribution and crop productivity. Responses to chilling include the
      accumulation of simple carbohydrates and changes in enzymes involved in their
      metabolism. Soluble carbohydrate levels and invertase, sucrose synthase (SS),
      sucrose-6-phosphate synthase (SPS) and alpha-amylase activities were analysed in
      cotyledons and embryonic axes of quinoa seedlings grown at 5 degrees C and 25
      degrees C in the dark. Significant differences in enzyme activities and
      carbohydrate levels were observed. Sucrose content in cotyledons was found to be
      similar in both treatments, while in embryonic axes there were differences.
      Invertase activity was the most sensitive to temperature in both organs; however,
      SS and SPS activities appear to be less stress-sensitive. Results suggest that 1)
      metabolism in germinating perispermic seeds would be different from endospermic
      seeds, 2) sucrose futile cycles would be operating in cotyledons, but not in
      embryonic axes of quinoa seedlings under our experimental conditions, 3) low
      temperature might induce different regulatory mechanisms on invertase, SS and SPS
      enzymes in both cotyledons and embryonic axes of quinoa seedlings, and 4) low
      temperature rather than water uptake would be mainly responsible for the changes
      observed in carbohydrate and related enzyme activities.

PMID- 15266716
TI  - Auxin autotrophic tobacco callus tissues resist oxidative stress: the importance
      of glutathione S-transferase and glutathione peroxidase activities in auxin
      heterotrophic and autotrophic calli.
AB  - Auxin autotrophic and heterotrophic tobacco callus lines were grown on MS medium
      with or without 100 mmol/L NaCl and growth and some of the stress-related
      activities, such as GPX, SOD, CAT, GST, GSH-PX, as well as the concentration of
      ethylene and H2O2, were measured and compared with each other. The auxin
      autotrophic calli grew slower, however, on the NaCl-containing medium the growth
      rate was higher than that of the heterotrophic cultures after two weeks of
      culturing. The stress-related ethylene production was lower in the autotrophic
      cultures and, contrary to the heterotrophic tissues, its level did not change
      significantly upon NaCl treatment. The guaiacol peroxidase (GPX) activities were
      higher in the autotrophic tissues in all cell fractions regardless of the
      presence of NaCl. Treated with NaCl, the GPX activities elevated in the soluble
      and covalently-bound fractions in the heterotrophic calli, but were not further
      increased in the autotrophic line. SOD and CAT activities were higher in the
      heterotrophic tissues, and were increased further by 100 mmol/L NaCl treatment.
      The GST and GSH-PX activities were higher in the autotrophic line, which might
      explain their enhanced stress tolerance. In the autotrophic tissues, the elevated
      antioxidant activities led to reduced levels of H2O2 and malondialdehyde; under
      mild NaCl stress, these levels decreased further. The lower growth rate and the
      effective protection against NaCl stress-induced oxidative damage of the
      autotrophic line can be explained by the cell wall-bound peroxidase and GSH-PX
      activities in the auxin autotrophic tissues. Their maintained growth rate
      indicates that the autotropic cultures were more resistant to exogenous H2O2.

PMID- 15266717
TI  - Effect of NaCl and mannitol iso-osmotic stresses on proline and free polyamine
      levels in embryogenic Fraxinus angustifolia callus.
AB  - With the aim to differentiate the ionic and osmotic components of salt stress,
      short and long-term changes in free polyamines and proline induced by iso-osmotic
      concentrations of NaCl (0.1 mol/L and 0.2 mol/L) and mannitol (0.2 mol/L and 0.4
      mol/L) were determined in Fraxinus angustifolia callus. The peculiarities of the
      short-term responses were: i) a very early (30 min) and temporary increase in
      Putrescine (Pu) and Spermine (Spm) as a consequence of salt treatment, and ii) a
      continuous accumulation of Spermidine (Spd) and Spm in response to mannitol. The
      changes of Proline (Pro) were quite limited both in the short and in the long
      term, and generally occurred later than Polyamine (PAs) changes took place,
      suggesting a regulatory mechanism of PAs metabolism on Pro biosynthesis. In the
      long-term, no drastic accumulations of Pro or PAs in response to NaCl and
      mannitol were observed, suggesting that their physiological role is unlikely to
      be that of osmo-compatible solutes in this plant system. The salt induced a
      higher callus growth inhibition effect than did mannitol and this inhibition was
      associated with the reduction of endogenous levels of PAs, especially Pu.
      However, while a diverging time course was observed under lethal salt
      concentration (0.2 mol/L NaCl), a high parallelism in the endogenous changes of
      Pro and Pu was observed under all non-lethal conditions (control--0.2 and 0.4
      mol/L mannitol--0.1 mol/L NaCl). Therefore the synchronous changes of Pro and Pu
      can be considered as a physiological trait associated with cell survival. These
      results indicate a strong metabolic co-ordination between PAs and Pro pathways
      and suggest that the metabolic fluxes through these pathways start competing only
      when the stress level is high enough to be lethal for cells.

PMID- 15266718
TI  - Changes in polyamine pattern are involved in floral initiation and development in
      Polianthes tuberosa.
AB  - In the day-neutral plant Polianthes tuberosa (cv. Double) putrescine and spermine
      in corms at the early floral initiation stage decreased by 26 and 36%,
      respectively, compared with that in the vegetative stage. In contrast, a sharp
      increase in spermidine and cadaverine titers in corms was recorded at the early
      floral initiation stage. However, cadaverine in corms disappeared at the flower
      development stage. Polyamines in the roots were generally lower than those in the
      leaves and corms. In no case was the change in endogenous polyamine titers in the
      roots and leaves associated with floral initiation and flower development in P.
      tuberosa. Exogenous application of spermidine at 5, 25 or 150 microg per plant at
      the vegetative stage did not affect flower primordium counts. However, addition
      of a spermidine synthase inhibitor, cyclohexylamine, at 150 or 250 microg per
      plant (each dose was applied two times in total at an interval of 4 days)
      significantly reduced flower primordium counts, indicating that spermidine is
      involved in floral initiation and floral development in P. tuberosa. In P.
      tuberosa corms at the vegetative stage arginine decarboxylase activity rises and
      decreases at the early floral initiation stage. In contrast, ornithine
      decarboxylase activity reaches the highest level at the early floral initiation
      stage and declines significantly at the vegetative stage. Results indicate that
      an increase in spermidine and a transient increase in cadaverine titers in the
      corms seem characteristic of early floral initiation in P. tuberosa. It is also
      suggested that a significant reduction in putrescine and spermine in the corms is
      involved in the early floral initiation in P. tuberosa.

PMID- 15266719
TI  - The impact of high CO2 concentrations on the structure and function of the
      photosynthetic apparatus and the role of polyamines.
AB  - Here we examined the influence of high CO2 concentrations on the structure and
      functioning of the photosynthetic apparatus in the unicellular green alga
      Scenedesmus obliquus. Presented in this work are: chlorophyll (Chl) a
      fluorescence induction kinetics, measurements of photosynthetic and respiration
      rates, estimation of Chl a/Chl b ratios, isolation and quantitative assessment of
      the photosynthetic subcomplexes, quantitative analyses of thylakoid bound
      polyamines, and experiments with exogenously supplied polyamines with cultures
      grown in low- and high-CO2 concentrations. Together, they indicated that high-CO2
      concentrations affect polyamines and, more specifically, increase the thylakoid
      bound putrescine (PUT) level that leads to an increase of the active reaction
      center density combined with a decrease in the LHCII-size and the ratio of LHCII
      oligomeres/LHCII-monomeres. This reorganization of the photosynthetic apparatus
      leads to enhanced photosynthetic rates, which in combination with the high-CO2
      concentrations, leads to an immense increase of biomass (800%). Further
      incubation for longer time periods under the same conditions produces, due to an
      increase in cell density, a self-shading effect and photoadaptation of the
      photosynthetic apparatus to low light conditions and therefore also results in
      reduction of the high-CO2 effect. The photoadaptation of the photosynthetic
      apparatus to high-light conditions (Kotzabasis et al. 1999) and the acclimation
      to high-CO2 concentrations (present work) lead to the same changes in the
      structure and function of the photosynthetic apparatus. These changes could be
      induced or inhibited through the manipulation of intracellular polyamines,
      especially through the putrescine/spermine ratio. The possibility that polyamines
      influence the photoadaptation of the photosynthetic apparatus and its acclimation
      to high-CO2 concentrations through a common mechanism is discussed.

PMID- 15266720
TI  - Unusual accumulation of S-methylmethionine in aerobic-etiolated and in anoxic
      rice seedlings: an 1H-NMR study.
AB  - An unknown signal at 2.93 ppm in 1H-NMR spectra of rice, Oryza sativa, was
      assigned to the methyl groups of sulphur-methylmethionine (SMM), thereby devising
      a new method for the determination of this compound. Rice seedlings growing
      aerobically in the dark and in the light engaged for the synthesis of SMM an
      amount of Met corresponding to 23 and 8%, respectively, of the total seed
      reserves of this amino acid. In etiolated shoots, SMM reached 1.2 micromol g(-1)
      fresh weight, an unusually high level in vegetative tissues of wild-type plants.
      This is compared to a value of 0.4 micromol g(-1) fresh weight in green tissues.
      A decreased demand for Met during growth caused the higher accumulation of SMM in
      etiolated, rather than green, tissues. At the same time, dark seedlings were
      endowed with a readily utilizable and translocable alternative form of Met, as
      shown by retrieval of SMM from the coleoptile. The importance of methyl group
      storage in SMM is shown by comparison with choline and choline phosphate pools.

PMID- 15266721
TI  - Gravitropism in Phycomyces: threshold determination on a clinostat centrifuge.
AB  - The absolute sensitivity of sporangiophores of Phycomyces blakesleeanus to
      centrifugal acceleration was determined on a clinostat centrifuge. The centrifuge
      provides centrifugal accelerations ranging from 10(-4) to 6 x g. The rotor of the
      centrifuge, which accommodates 96 culture vials with single sporangiophores, is
      clinostatted, that is, turning "head over", at slow speed (1 rev min(-1)) while
      it is running. The negative gravitropism of sporangiophores is characterized by
      two components: a polar angle, which is measured in the plane of bending, and an
      aiming-error angle, which indicates the deviation of the plane of bending from
      the vector of the centrifugal acceleration. Dose-response curves were generated
      for both angles with centrifugations lasting 3, 5, and 8 h. The threshold for the
      polar angle depends on the presence of statoliths, so-called octahedral protein
      crystals in the vacuoles. The albino strain C171 carAcarR (with crystals) has a
      threshold near 10(-2) x g while the albino strain C2 carAgeo-3 (without crystals)
      has a threshold of about 2 x 10(-1) x g. The threshold for the aiming error angle
      is ill defined and is between 10(-2) and 10(-1) x g. The threshold for the polar
      angle of the wild type NRRL 1555 (with crystals) is near 8 x 10(-2) x g.

PMID- 15266723
TI  - Barley anther culture: assessment of carbohydrate effects on embryo yield, green
      plant production and differential plastid development in relation with albinism.
AB  - Sugars and polyols were tested at different steps of anther culture in barley
      (Hordeum vulgare L.) to elucidate their influence on both the overall yield of
      androgenesis and the structure of plastids in relation to albinism. During the
      pretreatment period, the osmotic regulation in the medium was beneficial to
      microspore embryogenesis regardless of the type and concentration of the tested
      osmoticum. The use of mannitol (300 mOsm/kg), sorbitol (180 mOsm/kg), PEG (240
      mOsm/kg) and sucrose (180 mOsm/kg) gave the best results in terms of green plant
      production, although the influence of each substance differed according to the
      studied parameter. Similarly, during anther culture the regulation of the osmotic
      pressure in the medium had various effects, according to the osmoticum used. The
      best results were obtained using mannitol (364 mOsm/kg), providing 139.7 green
      plants per 100 plated anthers. Plastids were examined by electron microscopy
      following both pretreatment and culture. In the presence of mannitol and PEG,
      plastids did not accumulate starch at any stage of the protocol but they started
      to differentiate into chloroplasts in the microspore-derived embryos. Using
      sorbitol and sucrose, plastids differentiated poorly but accumulated large
      amounts of starch, suggesting that these sugars are metabolized by micropores and
      microspore derived structures. However, the accumulation of starch was not
      correlated with the occurrence of albinism. These results indicated that, in
      barley, the osmotic regulation was favourable to switch the microspore
      gametophytic program toward a sporophytic program regardless of the nature of the
      osmoticum. In addition, during the pretreatment period, mannito was found to be
      the most suitable osmoticum for subsequent embryo development.

PMID- 15266722
TI  - Expression analysis of buckwheat (Fagopyrum esculentum Moench) metallothionein
      like gene (MT3) under different stress and physiological conditions.
AB  - The buckwheat metallothionein-like (MT3) gene expression was studied throughout
      seed and leaf development, as well as under the influence of different external
      stimuli. MT3 mRNAs were detected from the early stage of seed development to the
      end of maturation, reaching the highest level during the mid-maturation stage.
      High MT3 mRNA level was noticed for both green and senescent leaves. The
      influence of raising Cu ion concentrations on MT3 gene expression was studied
      only in leaves, while the effect of Zn ions was analyzed through seed development
      as well. It was found that Cu and Zn ions had stimulatory effects on expression
      in leaves. MT3 expression was significantly enhanced in the early stage of seed
      development in response to Zn ions, while after this stage, influence of Zn ions
      was not detected. After H2O2/NaCl treatment, MT3 mRNA level was decreased in
      green leaves, contrary to senescent leaves where expression levels remained
      unchanged. H2O2 treatment caused the increase of MT3 mRNA levels in the mid
      maturation stage of seed development. NaCl had no effect on expression levels in
      seeds. According to obtained results, proposed functions in different plant
      organs regarding oxidative stress and metal homeostasis are discussed.

PMID- 15266724
TI  - Attachment and depression differentially influence nicotine dependence among male
      and female undergraduates: a preliminary study.
AB  - The authors surveyed a convenience sample of 208 undergraduate students who
      reported that they smoked cigarettes. The primary hypothesis they tested was
      whether gender predicted nicotine dependence. They further tested whether
      depression and attachment would mediate or moderate this relationship.
      Hierarchical regression analyses with social desirability and smoking stage of
      change entered as covariates indicated that women exhibited greater nicotine
      dependence than men did (p < .01). Lower attachment scores fully mediated this
      relationship, whereas elevated depression scores moderated the relationship.
      These findings suggest that depression and the inability to bond with peers may
      promote nicotine dependence among young female students.

PMID- 15266725
TI  - Smoking cessation and relapse prevention among undergraduate students: a pilot
      demonstration project.
AB  - The prevalence of college students' tobacco use is widely recognized, but
      successful cessation and relapse-prevention programs for these smokers have drawn
      little attention. The authors, who explored the feasibility of training peers to
      lead cessation and relapse-prevention programs for undergraduates, found a quit
      rate of 88.2%, suggesting that peers were effective facilitators. Relapse
      prevention interventions, which began immediately after participants quit
      smoking, included 6 monthly group programs and individual meetings. Each session
      provided education and training in stress management, nutrition and exercise
      habits, managing environmental smoking triggers, and coping in social situations.
      After participating in the relapse-prevention programs, 63.3% of the initial
      quitters remained smoke free, another indication that peers were effective
      facilitators. The success of the program, combined with the dearth of population
      specific cessation and relapse-prevention tools, suggests that college
      administrators and health educators should develop integrated tobacco management
      strategies on college campuses.

PMID- 15266726
TI  - A study of the relationship between protective behaviors and drinking
      consequences among undergraduate college students.
AB  - The authors identified the number, type, and frequency of protective behaviors
      that undergraduate college students who consume alcohol use to prevent alcohol
      related consequences. Their hypothesis was that students who engage in more types
      of protective behaviors with greater frequency would be less likely to experience
      alcohol-related consequences. Participants consisted of a randomly selected
      sample of 1,355 undergraduates aged 18 years and older at a large public
      university. Students completed a mailed questionnaire on alcohol and health
      behaviors in spring 2002. The findings (after adjustment for covariates)
      indicated that self-protective behaviors are inversely associated with alcohol
      related problems for women but not for men. The influences of gender and racial
      and ethnic differences are considered in relation to prevention and intervention
      programs aimed at reducing alcohol-related consequences on college campuses.

PMID- 15266727
TI  - Physical activity, exercise, and sedentary behavior in college students.
AB  - The authors examined the relationship between physical activity, exercise, and
      sedentary behaviors in 493 college students who were enrolled in 10 conditioning
      activity classes and had completed questionnaires at the beginning of the course.
      They analyzed sedentary activities and indicators of participation in exercise
      and physical activity by demographic variables. Surveyed men reported greater
      participation in physical activity and exercise than did women, and they also
      spent more time watching television/videos and using the computer. Older students
      were more likely to report more computer use, whereas younger students scored
      higher on several physical activity indicators. Of the sedentary behaviors, only
      computer use for men and television watching for women were negatively correlated
      with exercise and physical activity. In addition to accessibility and reinforcing
      properties of sedentary activities, the gender-related relationships between
      sedentary and active behaviors should be considered in designing interventions to
      promote exercise in this population.

PMID- 15266728
TI  - Effects of information on college students' perceptions of antidepressant
      medication.
AB  - The authors examined the impact of pharmaceutical companies' advertisements on
      college students' perceptions of depression and concomitant treatment with
      antidepressants among 13 male and 31 female undergraduates from a midwestern
      university. The students were randomly assigned to groups that read either
      pharmaceutical company advertisements or scientific information about depression
      and its treatment. The analysis revealed that 40% of the women in the
      advertisement condition as opposed to 1 woman (6%) in the scientific condition
      rated themselves as having mild, moderate, or severe depression on the Beck
      Depression Inventory, second edition. Women in the advertisement condition were
      significantly more likely to believe that depression required treatment with
      antidepressant medication and were more willing than women in the scientific
      condition to suggest antidepressant treatment to others.

PMID- 15266729
TI  - Improving patient satisfaction with waiting time.
AB  - Waiting times are a significant component of patient satisfaction. A patient
      satisfaction survey performed in the author's health center showed that students
      rated waiting time lowest of the listed categories--A ratings of 58% overall, 63%
      for scheduled appointments, and 41% for the walk-in clinic. The center used a
      quality improvement process and instituted schedule and reception area changes. A
      follow-up survey 3 months later showed A ratings of 73% overall, 81% for
      scheduled appointments, and 56% for the walk-in clinic. A repeat survey 4 months
      later showed A satisfaction ratings of 79% overall, 85% for scheduled
      appointments, and 68% for the walk-in clinic. The author discusses strategies the
      center used to improve patient satisfaction with waiting time.

PMID- 15266730
TI  - Something has to give.

PMID- 15266731
TI  - Handpiece speed and postoperative outcomes in third molar surgery.
AB  - OBJECTIVE: This study was performed to assess surgical outcomes when externally
      irrigated slow-speed surgical handpieces (30,000 rpm) were compared to externally
      irrigated high-speed handpieces (90,000 rpm) in the removal of impacted lower
      third molar teeth. STUDY DESIGN: One hundred patients with bilater ally impacted
      third molar s were enrolled in the study; 53 remained to completion. Each patient
      served as his/her own control. The experimental side was treated using a 30,000
      rpm electric rotary drill incorporating irrigation, while the control side was
      treated using the same drill system, but with a 90,000 rpm handpiece. Drill
      speeds used were alternated between the right and left sides of patients to avoid
      bias introduced by the dominant hand of the surgeon. Patients were blinded to
      drill speed, and were asked to complete a standardized pain/swelling
      questionnaire for seven days immediately following surgery. Data was analyzed to
      determine differences in pain, swelling, and complications in relation to the
      drill type used. RESULTS: No statistically significant differences were found in
      degree of pain, swelling, or complications when the slower drill was compared to
      the high-speed instrument. CONCLUSIONS: The study suggests that there is no
      difference in postoperative outcome when impacted third molar teeth are removed
      with either slow- or high-speed instrumentation, and that the choice of the drill
      type should be determined solely by the preference of the operator.

PMID- 15266732
TI  - Dental fracture fragment attachment: fracture model and luting agent comparisons.
AB  - PURPOSE: The purpose of this study was twofold: 1. To compare two different
      research models for simulating a traumatic anterior tooth fracture: the blunt
      trauma method (standard method) and an AL2O3 sectioning method (experimental
      method). 2. To compare the bond strength of tooth fragments bonded with resin
      modified glass ionomer vs. a light cured composite resin. METHODS: Two hundred
      bovine incisors were used in the study and kept in plain tap water throughout.
      The study consisted of five basic steps: 1. Fracture of the teeth by either blunt
      trauma (chisel and hammer) or AL2O3 sectioning disc. 2. Luting of the fractured
      fragments back to the teeth using either a composite resin or resin modified
      glass ionomer. 3. Thermocycling of the repaired teeth. 4. Dislodging the teeth to
      determine the strength of repair. 5. Determination of fracture type. RESULTS: One
      way ANOVA revealed a statistically significant difference in the forces required
      to fracture the resin modified glass ionomer and composite resin regardless of
      whether the teeth were originally fractured with the blunt force method (p=0.030)
      or the disc sectioning method (p=.001). One-way ANOVA also revealed a
      statistically significant difference between the forces required for fracture by
      blunt trauma and the disc fracture techniques with the resin modified glass
      ionomer group (p=0.000345). However, there was no significant difference when the
      two techniques were compared for the composite resin (p= 0.2941). CONCLUSIONS: 1.
      The resin modified glass ionomer was significantly stronger than the composite
      resin when both the blunt trauma and the disc fracture techniques were employed.
      2. The study's results do not support substituting the ease of the AL2O3 disc for
      the more time-consuming blunt trauma method.

PMID- 15266733
TI  - Esthetic contemporary dentistry and soft tissue recontouring with the diode
      laser.

PMID- 15266734
TI  - Getting started in digital photography.

PMID- 15266735
TI  - Anthrax, heart disease, and your toothbrush: an interview with 2004 IDA Annual
      Session presenter Dr. Tom Glass.

PMID- 15266736
TI  - A classification system for mosquito life cycles: life cycle types for mosquitoes
      of the northeastern United States.
AB  - A system for the classification of mosquito life cycle types is presented for
      mosquito species found in the northeastern United States. Primary subdivisions
      include Univoltine Aedine, Multivoltine Aedine, Multivoltine Culex/Anopheles, and
      Unique Life Cycle Types. A montotypic subdivision groups life cycle types
      restricted to single species. The classification system recognizes 11 shared life
      cycle types and three that are limited to single species. Criteria for
      assignments include: 1) where the eggs are laid, 2) typical larval habitat, 3)
      number of generations per year, and 4) stage of the life cycle that overwinters.
      The 14 types in the northeast have been named for common model species. A list of
      species for each life cycle type is provided to serve as a teaching aid for
      students of mosquito biology.

PMID- 15266737
TI  - Food as a limiting factor for Aedes aegypti in water-storage containers.
AB  - An understanding of the ecological factors that regulate natural populations of
      Aedes aegypti mosquitoes can improve control and reduce the incidence of dengue
      (DF) and dengue hemorrhagic fever (DHF) in tropical areas. We investigated
      whether immature Ae. aegypti in water-storage containers from an urban area were
      under food limitation. We used starvation resistance (number of days alive
      without food) as an indicator of the feeding history in third-instar Ae. aegypti
      larvae. Resistance to starvation and other measures of immature success, such as
      development time, survival, and adult mass, were investigated across a wide range
      of feeding conditions in the laboratory. Resistance to starvation of third-instar
      larvae and body mass of adults emerging from pupae collected in water-storage
      containers in an urban area were compared with the laboratory results. If
      resistance to starvation and adult mass of field-collected Ae. aegypti
      corresponded with the lower levels of feeding in the laboratory, then food
      limitation could be inferred in field-collected larvae. Results showed that
      resistance to starvation was well correlated with previous feeding levels and
      with the other measures of immature success. Both resistance to starvation and
      adult body mass of field-collected specimens corresponded with the lower levels
      of feeding in the laboratory. Therefore, it was concluded that food limitation or
      competition is likely to be a regulatory factor in water-storage containers in
      the urban area. It is recommended that any control measure applied to immature
      Ae. aegypti in water-storage containers should eliminate all or most of the
      individuals, otherwise unintended, undesirable results might occur, such as the
      production of more and larger adults.

PMID- 15266738
TI  - Review of the anopheline mosquitoes of Myanmar.
AB  - This study examined the species of anopheline mosquitoes in Myanmar. Out of 36
      species of anophelines distributed throughout the country, ten species were found
      to be infected with the malaria parasite. These vectors are presented with
      particular reference to their distribution and a summary of bionomics and
      infection rates.

PMID- 15266739
TI  - Ecology of Anaplasma phagocytophilum and Borrelia burgdorferi in the western
      United States.
AB  - We discuss the ecology of Anaplasma phagocytophilum and Borrelia burgdorferi in
      the western U.S. These agents, while emerging in the eastern U.S., remain stable
      or rare in the west. In the western U.S., tick vectors and mammalian hosts for B.
      burgdorferi and A. phagocytophilum are distinct from those in the eastern U.S.
      and considerably more variable. Spatial complexity, local extinctions, and low
      levels of movement among foci may determine the distribution and prevalence of
      these agents. High-prevalence A. phagocytophilum patches may be transient,
      possibly as host individuals become immune. Thus, A. phagocytophilum in
      California could exist in a metapopulation of interacting patches. Local dynamics
      are sensitive to host population sizes and minimum tick infestation levels.
      Determining critical values for these key factors and their interactions will be
      important for predicting the level and distribution of future infections in the
      western U.S.

PMID- 15266740
TI  - A morphological investigation of Culicoides spp. biting midges (Diptera:
      Ceratopogonidae) from the Caribbean.
AB  - Features of the antennae, maxillary palps, and mouthparts of the females of seven
      species of Culicoides spp. biting midges collected from a montane rainforest site
      in Trinidad, West Indies, were studied by light and scanning electron microscopy.
      Comparisons were made with two British species, Culicoides impunctatus and
      Culicoides nubeculosus. Species-specific differences were demonstrated in the
      camber and pitch of mandibular teeth, the size and shape of the subapical labral
      sensilla, the size and depth of the palpal sensory pit, and the number and shape
      of heads of the palpal sensilla. Counts of sensilla coeloconica and palpal
      sensilla were suggested as being contributory features for the prediction of host
      preference, indicating that Culicoides darlingtonae, Culicoides glabellus,
      Culicoides insinuatus, Culicoides paraensis, and Culicoides pseudodiabolicus were
      probably mammalophilic species. The host preferences of Culicoides heliconiae and
      Culicoides flavivenula could not be determined accurately.

PMID- 15266741
TI  - Abundance and temporal distribution of Ornithonyssus sylviarum Canestrini and
      Fanzago (Acarina: Mesostigmata) in gray catbird (Dumatella carolinensis) nests.
AB  - The northern fowl mite, Ornithonyssus sylviarum Canestrini and Fanzago, is a
      common ectoparasite of wild birds. Despite its ability to transmit eastern equine
      encephalitis (EEE) virus under laboratory conditions and potential for
      involvement in the natural EEE virus cycle, we know little about its abundance or
      temporal distribution in nature. From June to August 2000, we studied the
      abundance of O. sylviarum in the nests of gray catbirds (Dumatella carolinensis),
      a reservoir host for EEE virus, at Killbuck Marsh Wildlife Area (KMWA), a known
      EEE virus focus in Wayne County, Ohio. A total of 7,883 O. sylviarum, including
      1,910 adults and 5,973 protonymphs, were recovered from 23 of 26 gray catbird
      nests collected during various phases of the nesting cycle. We found no
      association between mite abundance and number of catbird nestlings in successful
      nests. However, mite abundance increased significantly with date of nest
      collection and peaked in late July when transmission of EEE virus is likely to
      occur at KMWA. We therefore suggest that O. sylviarum may contribute to the
      transmission of EEE virus among gray catbirds at KMWA.

PMID- 15266742
TI  - Evaluation of attractants and egg-laying substrate preference for oviposition by
      Aedes albopictus (Diptera: Culicidae).
AB  - Evaluation of oviposition attractants and substrate preferences of Aedes
      albopictus was carried out under laboratory and field conditions. To obtain
      candidate oviposition substances we used a water rinse of 3 mollusk species:
      blood cockle (Anadara granosa), carpet shell (Paphia undulata), and sea mussel
      (Mytilus smaragdinus), and the giant tiger prawn (Penaeus monodon). The rinse
      water of carpet shell and giant tiger prawn showed higher attractiveness for
      ovipostion than the other candidate attractants. The filter paper substrate
      received fewer eggs than the other two substrates. There was no significant
      difference between the mean number of eggs laid on hardboard paddles and sponge
      sheets. The hatching rate of Ae. albopictus eggs laid on hardboard paddles was
      higher than those from the filter papers and sponge sheets. The sponge had lethal
      effects on Ae. albopictus eggs, and very few eggs laid on sponge hatched. In
      field experiments, evaluation of attractiveness of carpet shell rinse in ovitraps
      lined with sponge sheet as egg-laying substrate was carried out in various
      habitats and different areas of Thailand. The mean number of eggs in traps
      containing carpet shell rinse was significantly higher than those laid in
      rainwater traps. These studies reveal that the carpet shell and giant tiger prawn
      rinses are sources of oviposition attractant for Ae. albopictus under both
      laboratory and field conditions and could possibly be used as an attractant in
      surveillance and control.

PMID- 15266743
TI  - Seroprevalence of eastern equine encephalomyelitis virus in birds and larval
      survey of Culiseta melanura Coquillett during an interepizootic period in central
      Ohio.
AB  - From June through August in 1999 and 2000, we conducted an avian serosurvey for
      eastern equine encephalomyelitis (EEE) virus at Killbuck Marsh Wildlife Area
      (KMWA), a focus of infection in central Ohio. We also monitored abundance of the
      suspected enzootic vector, Culiseta melanura Coquillett, in Brown's Lake Bog, an
      adjacent wetland. Of the 363 birds of 30 species sampled in 1999, three gray
      catbirds (Dumetella carolinensis) were positive for antibodies to EEE virus,
      representing 1.2% of the avian samples and 4.2% of the gray catbirds sampled.
      Given these results and the abundance of gray catbirds at this site, this species
      became the focus of our sampling efforts in 2000. However, none of the 109
      samples collected from 98 catbirds in 2000 was positive for the virus. Culiseta
      melanura adults were monitored using resting boxes and CDC CO, light traps at
      both sites in 1999. Culiseta melanura larvae were monitored in 1999 and 2000 at
      Brown's Lake Bog, the closest known source of this species, approximately 5km
      from the avian serosurvey site. We suggest that dry conditions reduced the
      breeding and abundance of Cs. melanura in 2000 and possibly the transmission of
      EEE virus at KMWA.

PMID- 15266744
TI  - Observations on first and second-instar larvae of Megaselia scalaris (Loew)
      (Diptera: Phoridae).
AB  - The ultrastructure of the first and second-instar larvae of Megaselia scalaris
      (Loew) was studied using scanning electron microscopy (SEM). Significant changes
      in morphological features were observed in the anterior and posterior spiracles,
      but only minimal changes in the labium and mouthhooks were seen. The
      ultrastructure of M. scalaris larvae not only provides chronological
      transformation of their larval instars, but it can also be used to explain their
      feeding behavior and mode of respiration. In addition, morphological structures
      useful for specific identification of first or second-instar larvae collected
      from human corpses may be used in forensic investigations.

PMID- 15266745
TI  - Antagonistic effects of energy status on meal size and egg-batch size of Aedes
      aegypti (Diptera: Culicidae).
AB  - The effect of sugar feeding on egg-batch size in Aedes aegypti was examined in a
      way that would distinguish between the roles of a recent sugar meal (full vs.
      empty crop) and of repeated sugar feeding and digestion (high vs. low energy
      reserves). Egg numbers of females representing the four combinations of these
      characteristics (full crop/high reserves, full crop/low reserves, empty crop/high
      reserves, empty crop/low reserves) were counted during their first gonotrophic
      cycle. In addition, the sizes of their replete sugar meals and human blood meals
      were measured to understand the interactions between them. Results demonstrated
      that blood-fed mosquitoes with full crops and low energy reserves produced the
      fewest eggs (mean = 56.2); those with empty crops and high energy reserves
      produced the most eggs (mean = 84.6); and those with the opposite combinations
      (full/high and empty/ low) had an intermediate fecundity (mean = 75.2 and 76.9,
      respectively). This ranking of fecundities did not correspond to blood-meal size
      ranks, owing to direct and indirect effects of energy reserves on meal sizes and
      egg number. Full-crop females with low reserves ingested the smallest blood meals
      (mean = 0.62 mg) and had the lowest fecundities. Full-crop females with high
      reserves ingested more blood (mean = 0.82 mg) and produced more eggs. But empty
      crop females with low reserves ingested the largest blood meals (mean = 1.19 mg),
      yet produced significantly fewer eggs than their high-reserve counterparts, which
      took smaller blood meals (mean = 0.99 mg). These results demonstrate extremes in
      the reproductive penalty of crop sugar and the reproductive reward of digested
      sugar. Energy reserves and an empty crop are similarly valuable in promoting
      fecundity at the time blood is taken.

PMID- 15266746
TI  - The invasion of urban forest by dengue vectors in Rio de Janeiro.
AB  - The invasion of a secondary forest within the city of Rio de Janeiro by Aedes
      aegypti and Ae. albopictus was evaluated from July 1997 to June 1998 through
      collections of immature stages in ovitraps set at 1 m, 10 m, 100 m, 500 m, and
      1,000 m into the forest from houses on the periphery. Both mosquito species were
      much more abundant close to houses (1-10 m). Aedes aegypti was not collected
      beyond 100 m, while Ae. albopictus was the most abundant species overall and in
      ovitraps at all distances from houses. Abundances of Ae. albopictus were
      significantly correlated with time-lagged rainfall and with abundances of Ae.
      aegypti. Co-occurrences of Ae. albopictus in traps with Ae. aegypti and Limatus
      durhami, but not with Culex dolosus, were more likely close to houses. The
      results suggest that the urban forest is a refuge for both Aedes species, but
      especially for Ae. albopictus, whose abundance both near houses and in the forest
      raises concern that this invader may transmit arboviruses to humans that are
      presently restricted to the sylvan environment.

PMID- 15266747
TI  - The in vitro effect of albendazole, ivermectin, diethylcarbamazine, and their
      combinations against infective third-stage larvae of nocturnally subperiodic
      Brugia malayi (Narathiwat strain): scanning electron microscopy.
AB  - Scanning electron microscopy (SEM) was employed to observe the effects of
      ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) alone, and the
      drugs in combination (ALB+IVM and ALB+DEC) against infective third stage larvae
      (L3) of nocturnally subperiodic (NSP) Brugia malayi (Narathiwat strain) in vitro.
      IVM, at a concentration of 10(-4) M, killed L3 within 1-2 h. The SEM data showed
      damage to the L3 surface and loss of regular cuticular annulations. The cuticles
      were grooved in the middle region of the body. In comparison with normal L3
      before treatment with IVM, the cuticular surface showed transversed striations
      with periodic annulations. The result demonstrated that IVM showed a larvicidal
      activity against L3 of NSP B. malayi cultivated in vitro. Compared with those
      larvae in the control group, the treated larvae had no morphological changes in
      the cuticular surface at the head, body, and tail regions after cultivation with
      all drugs alone, and in their combinations at a concentration of 10(-5) M for 7
      d. In this system, and at that concentration, only the larvae cultured with ALB
      alone remained highly motile. Although no morphological changes had been observed
      by SEM, those drugs used alone (IVM and DEC) and in combinations (ALB+IVM and
      ALB+DEC), reduced larval motility throughout the experiments at a concentration
      of 10(-5) M. The minimum lethal concentration (MIC) of IVM against NSP B. malayi
      was 10(-4) M.

PMID- 15266748
TI  - Mosquito larvae (Diptera: Culicidae) in snow-melt pools in a Swedish Lapland
      area.
AB  - Culicid larvae were collected in snow-melt pools during the first half of June
      from 1975-1977 and 1995-1996 in the Abisko Valley, Torne Lapmark, northern
      Sweden. Twelve species were collected from 102 pools and 81 localities with 7,914
      specimens (elevations from 300 to 650 m a.s.l.). Fourteen species are now known
      from the area. Ten types of larval habitats were classified and ten species were
      statistically analyzed on pooled values over all years for abundance,
      coexistence, and diversity. The greatest abundance of individuals had pools with
      Carex spp. on the bottom. Most widespread and abundant were Oc. hexodontus
      (Dyar), Oc. communis (DeGeer), Oc. pullatus (Coquillett), and Oc. punctor
      (Kirby). The two circumpolar, arctic species, Oc. nigripes (Zetterstedt) and Oc.
      impiger (Walker), were mainly confined to elevations above 400 m a.s.l. In such
      marginal habitats as these pools, exposed to variable abitotic conditions, the
      phenology of species was rather constant. Species diversity varied somewhat
      between habitats. Oc. hexodontus, Oc. communis, and Oc. pullatus most often
      occupied pools as single species. Oc. communis and Oc. hexodontus had the highest
      values for coexistence and also occurred with Oc. punctor. The habitats that were
      richest in species were those without vegetation or with detritus on the bottom
      and surrounded by Empetrum nigrum and Betula nana. These habitats contained
      between eight and ten species. Species abundance and coexistence over the years
      showed no stable species patterns for the habitat types in the area.

PMID- 15266749
TI  - Laboratory and field studies of Macrocyclops albidus (Crustacea: Copepoda) for
      biological control of mosquitoes in artificial containers in a subtropical
      environment.
AB  - The cyclopoid copepod Macrocyclops albidus (Jurine) was tested as a potential
      biological control agent of mosquitoes in laboratory microcosms, in controlled
      field conditions, and in a 22-mo field experiment using discarded tires. The
      predator was highly efficient in controlling mosquitoes in all three settings,
      reaching close to 90% reduction in larval survival under field conditions and
      exceeding the recommended predation rates for effective mosquito control in
      laboratory experiments. The predator was most effective on 1-4-d-old larvae.
      Alternate food and habitat structure significantly influenced the predation rates
      on mosquito larvae. Once established, the copepod was able to maintain
      reproducing populations in the field for the duration of the experiments.
      However, the predator failed to establish populations at four of the experimental
      field sites. Two of the failures can be attributed to characteristics of the
      individual tires, such as leaching chemicals, whereas the other two were probably
      due to site-specific factors. This copepod species is a promising candidate for
      control of mosquito larvae because it is a widespread and highly effective
      predator that is capable of establishing and maintaining populations under a wide
      variety of field conditions. Additionally, M. albidus is relatively easy to
      culture, maintain, and deliver to the target areas.

PMID- 15266750
TI  - Mating affects egg maturation in Anopheles gambiae Giles (Diptera: Culicidae).
AB  - The effect of mating on egg development and the size of the female accessory
      glands during the gonotrophic cycle of Anopheles gambiae was investigated.
      Although females that received a measured meal of blood were more likely to
      produce an egg batch when they were mated, the increased reproduction was not the
      result of male accessory gland substances. Changes in the size of the female
      accessory gland were not observed after mating nor at any time during the
      gonotrophic cycle, but there was a more rapid increase in its size following
      emergence in mated females.

PMID- 15266751
TI  - Flight performance of the malaria vectors Anopheles gambiae and Anopheles
      atroparvus.
AB  - The flight potential and metabolism of two malaria vectors, Anopheles gambiae
      s.str. and An. atroparvus, were analyzed on flightmills. The flight distance, the
      flight time, and individual flight activities of females were recorded during 22
      h flight trials. The glycogen and lipid before flight, after flight, and of
      unflown controls were measured for starved, sugar-, or blood-fed females. Maximal
      flight distances of An. gambiae were 9 km when sugar-fed and 10 km when blood
      fed, while in starved females it was below 3 km and the average speed was around
      1 km/h. In Anopheles atroparvus, the maximal flight distances were 10-12 km when
      sugar-fed, 4.5 km when blood-fed, and below 3.5 km when starved, with an average
      speed of 1.3 km/h. Flight performances consisted of 1-4 h intervals of continuous
      flights, but mainly of bouts shorter than one h, randomly distributed during the
      long flight trials in both species. An. gambiae utilized an average of 47% of its
      pre-flight carbohydrate reserves for survival and 38% for flight at a rate of
      0.07 cal/h/female. After a blood meal they utilized 11% for survival and 61% for
      flight at a rate of 0.04 cal/h. At the same time, 25% of the pre-flight lipid was
      mobilized for flight at a rate of 0.09 cal/h when sugar-fed and 22% when blood
      fed at a rate of 0.06 cal/h; lipid was barely mobilized for survival. An.
      atroparvus differed: carbohydrate mobilization was 28% for survival and 41% for
      flight at a rate of 0.15 cal/h when sugar-fed; lipid mobilization for flight was
      only 13% at a rate of 0.06 cal/h. After a blood meal only 2% of the pre-flight
      lipid was used (0.02 cal/h). The contribution of carbohydrate reserves for flight
      metabolism at the high rate of 0.21 cal/h could not be fully elucidated because
      its decrease coincided with a pronounced resynthesis from the blood meal. An.
      atroparvus always depended on sugar meals for its flight activities and barely
      utilized lipid reserves. An. gambiae was independent of sugar sources for strong
      flights due to its early blood feeding and because of its equicaloric lipid
      mobilization during flights. Strong evidence for lipid oxidation during its
      flight is discussed.

PMID- 15266752
TI  - Nectar and honeydew feeding of Phlebotomus papatasi in a focus of Leishmania
      major in Neot Hakikar oasis.
AB  - Feeding of Phlebotomus papatasi Scopoli on nectar and honeydew was investigated
      in Neot Hakikar, an oasis in the southern Jordan Valley. Sand flies were caught
      with miniature light traps in cleared areas with large Tamarix nilotica Bunge
      bushes, in colonies of the sandrat Psammomys obesus Cretzschmar. Fly series were
      trapped and compared according to the condition of T. nilotica bushes: with
      flowers, soiled with honeydew excreted by cicadas, or without flowers. Near
      flowering bushes the catch was five times greater (7.9: 1.6 flies/trap) and the
      proportion of sugar-positive flies was also much greater (49.9:17.3%) than near
      bushes without flowers. The catch was three times greater (6.6:2.2 flies/trap)
      near cicada- infested than near uninfested bushes. Color markers within the gut,
      obtained from infested or uninfested bushes that had been sprayed with food dye,
      indicated feeding of 33.2% and 4.5% of these series, respectively. Sand flies
      were strongly attracted to flowers of T. nilotica. In similar trap series, those
      baited with flowering branches caught 231 flies, whereas with baits of honeydew-
      soiled branches, control regular branches or wet filter paper, the catch ranged
      between 11 to 15 flies. This study is the first evidence of nectar feeding by
      sand flies in the field and it indicates that nectar may be an important and an
      attractive source of sugar.

PMID- 15266753
TI  - Oviposition by Aedes aegypti (Diptera: Culicidae) in relation to conspecific
      larvae infected with internal symbiotes.
AB  - Female mosquitoes use abiotic and biotic factors, such as the presence of heavy
      metals or parasites, to determine the acceptability of oviposition sites. Some
      biotic factors can originate from mosquito larvae. When mosquito larvae are
      starved or infected with trematode metacercaria, they render associated water
      unacceptable to ovipositioning females. Internal symbiotes are common in wild
      mosquito populations, and I tested whether or not larvae of Aedes aegypti
      infected with a gregarine (Ascogregarina taiwanensis), a yeast (Candida near
      pseudoglaebosa), or a trichomycete (Smittium morbosum) rendered their rearing
      water unacceptable to oviposting mosquitoes. Infections with S. morbosum had no
      effect on the acceptability of the associated rearing water when compared to
      rearing water from uninfected larvae. However, the rearing water from larvae
      infected with A. taiwanensis or C. near pseudoglaebosa was more acceptable to
      ovipositing females than was distilled water or rearing water from uninfected
      larvae. Ovipositing female mosquitoes either preferred or were neutral to rearing
      water from larvae with gut symbiotes.

PMID- 15266754
TI  - Thermal accumulation and the early development of Ixodes scapularis.
AB  - We examined the relationship between the accumulation of thermal energy and the
      onset of oviposition and eclosion of the northern deer tick, Ixodes scapularis,
      and explored the usefulness of comparing degree days (DD) required for larval
      emergence with area-wide National Weather Service (NWS) data to construct maps
      indicating where the establishment of this vector tick would be climatologically
      constrained. Initially, the validity of basal temperatures for egg and larval
      development was confirmed by prolonged incubations of gravid females and eggs at
      6 degrees C and 10 degrees C respectively. Next, the number of DD accumulated in
      situ from the placement of gravid females to oviposition, and from oviposition to
      larval emergence, were measured using temperature data loggers placed next to
      fall- and spring-fed ticks held within individual vials under leaf litter in
      multiple enclosures located in diverse biophysical regions of Maine. Finally,
      when it was found that total DD to larval emergence, as measured in ambient air
      above the enclosures, compared favorably with DD accumulated simultaneously at
      nearby NWS stations, maps were constructed, based on archived NWS data, to
      demonstrate where temperatures were sufficient to allow the hatching of larvae
      both within one season and over the last three decades as I. scapularis has
      advanced into northern New England.

PMID- 15266755
TI  - Community ecology of small mammal populations in Panama following an outbreak of
      Hantavirus pulmonary syndrome.
AB  - In late 1999 and early 2000, an outbreak of hantavirus pulmonary syndrome (HPS)
      occurred in and around Los Santos, on the Azuero Peninsula of southwestern
      Panama. This HPS episode, resulting in 22% case fatality, was linked to the Costa
      Rican pigmy rice rat, Oligoryzomys fulvescens costaricensis, which harbored a
      then undescribed hantavirus, Choclo virus. In addition, Cherrie's cane rat,
      Zygodontomys brevicauda cherriei, was identified as carrying a distinct
      hantavirus, Calabazo virus with no known pathogenicity to humans. Herein we
      present the ecological results of the outbreak investigations in the Azuero
      region. A total of 164 animals were captured, of which 126 were potential small,
      non-volant mammal hosts of a hantavirus: rodents in the family Muridae. There
      were significant differences in small mammal community structure between case
      sites and a negative control site. Differences were manifest in ecological
      measures of species diversity and in species evenness and heterogeneity measures,
      as indicated by Pairwise Euclidian distances and Morisita indices of community
      similarity. Our analyses suggest that human activities (i.e., deforestation for
      cattle ranching) coupled with environmental factors (i.e., increased
      precipitation) may have synergistically coalesced for an increased risk of HPS to
      area residents.

PMID- 15266757
TI  - Selected literature references to vector ecology--October 2003-March 2004.

PMID- 15266756
TI  - Clearing technique to examine the cephalopharyngeal skeletons of blow fly larvae.

PMID- 15266758
TI  - Benefits and limitations of ultrasonographic evaluation of uterine adnexal
      lesions in early detection of ovarian cancer.
AB  - Ovarian cancer is the most frequent cause of death from gynaecological
      malignancies in the Western world. Most cases of epithelial ovarian cancer are
      detected at late stages and the resultant overall five-year survival is poor.
      However, when epithelial ovarian cancer is detected with the disease confined to
      the ovary the prognosis is favorable. Transvaginal gray-scale ultrasonography and
      colour Doppler assessment of blood flow have been evaluated as methods to predict
      risk of malignancy in ovarian tumours. In order to reduce the number of
      unnecessary surgical procedures for uterine adnexal tumours, ultrasonomorphologic
      scoring systems have been developed, assigning numerical ultrasonographic
      parameters of the tumours. However, the positive predictive value of these
      scoring systems is low and this is due to the fact that the appearance of many
      benign ovarian lesions overlaps with that of malignant disease. In addition, some
      ovarian malignancies are ultrasonographically detected as simple cysts without
      exhibiting a complex morphology. Moreover, the cut-off size of uterine adnexal
      tumours for surgical intervention in the early detection of cancer is not yet
      well determined. The application of colour blood-flow imaging is very helpful in
      the detection of uterine adnexal malignancy because of the presence of
      neovascularization in malignant tumours. When gray-scale ultrasonography detects
      the presence of septum or papillary projections or solid components in uterine
      adnexal lesions and Doppler flow is present within these lesions malignancy is
      likely. However, the detection of vascularity within the papillary projection of
      a malignant tumour may not be detected when it is very small. When colour-flow
      imaging is used in premenopausal patients attention is needed to avoid confusion
      of luteal flow with flow of cystic lesions. Initial reports using pulsed Doppler
      ultrasonography showed high sensitivity and specificity in the detection of
      ovarian cancer when levels of the resistive index (RI) less than 0.4 and levels
      of the pulsatility index (PI) less than 1 were used. Subsequent studies have
      shown considerable overlap of RI and PI rates between benign and malignant
      uterine adnexal masses, suggesting that pulsed Doppler ultrasonography is not an
      independent indicator for malignancy. Serum CA-125 levels have been used in
      conjunction with ultrasonography to identify as many of the false-positive
      results in order to avoid unnecessary surgery. In postmenopausal women with a
      uterine adnexal mass the combination of physical examination with serum CA-125
      levels and pelvic ultrasound scan seems to improve the sensitivity and
      specificity of predicting adnexal malignancies. In contrast, in premenopausal
      women the consideration of CA-125 levels with Doppler ultrasonographic findings
      might confuse the differential diagnosis of ovarian masses. In conclusion,
      accurate selection of patients with uterine adnexal tumours for surgical
      intervention is not provided by pelvic ultrasonography. Pelvic ultrasonography as
      a screening method for the early detetection of ovarian cancer should be probably
      limited to those women who are at increased risk for development of ovarian
      cancer and not in the general population.

PMID- 15266760
TI  - Serum and follicular fluid leptin levels in patients undergoing controlled
      ovarian hyperstimulation for in vitro fertilization cycle.
AB  - OBJECTIVE: To determine serum and follicular fluid leptin levels in patients
      undergoing controlled ovarian hyperstimulation (COH) for an in vitro
      fertilization-embryo transfer (IVF-ET) cycle and their possible correlation to
      COH variables. SETTING: Large university-based IVF unit. PATIENTS: 16 consecutive
      patients undergoing our routine IVF long gonadotrophin-releasing hormone-analog
      protocol. INTERVENTIONS AIND MAIN OUTCOME MEASURES: Blood was drawn three times
      during the COH cycle: 1) day on which adequate suppression was obtained (Day-S);
      2) day of or prior to human chorionic gonadotrophin (hCG) administration (Day
      hCG); and 3) day of ovum pick-up (Day-OPU). Levels of sex steroids and serum and
      follicular fluid leptin were compared among the three time points. Serum leptin
      was measured with a commercial two-site immunoradiometric assay. RESULTS: Results
      showed significantly higher levels of serum leptin on Day-OPU and Day-hCG than on
      Day-S, and significantly higher follicular than serum leptin levels on Day-OPU.
      Though a significant correlation was observed between serum leptin and body mass
      index (BMI), no correlations were found between serum or follicular fluid leptin
      and serum sex-steroid levels or IVF treatment variables. CONCLUSION: While serum
      leptin increases during COH for IVF, there is apparently no correlation of serum
      and follicular leptin levels with sex-steroid levels or IVF outcome.

PMID- 15266759
TI  - Neither sildenafil nor vaginal estradiol improves endometrial thickness in women
      with thin endometria after taking oral estradiol in graduating dosages.
AB  - PURPOSE: To determine if sildenafil improves endometrial thickness better than
      vaginal estradiol (E2) in women with a history of thin endometria. METHODS: Women
      failing to attain an 8 mm endometrial thickness on either the oocyte retrieval
      cycle or their first frozen embryo transfer (ET) despite an oral graduated E2
      regimen were treated again with graduated oral E2 and were also randomly assigned
      to vaginal sildenafil or vaginal E2 therapy. Endometrial thickness was compared
      between the groups. RESULTS: Neither vaginal E2 nor sildenafil significantly
      improved endometrial thickness or blood flow in the subsequent frozen ET-cycle.
      CONCLUSIONS: These data fail to corroborate previous claims that 25 mg sildenafil
      four times daily intravaginally can improve endometrial thickness.

PMID- 15266761
TI  - Correlation of endoscopic interpretation of endometriosis with histological
      verification.
AB  - INTRODUCTION: In this study we correlate the laparoscopic findings of
      endometriosis with the histological confirmation of the disease over a period of
      two years. MATERIALS AND METHODS: One hundred and sixty-four laparoscopies
      performed at the Department of Gynecology & Obstetrics, University of Kiel, over
      a two-year period were reviewed for laparoscopic findings and histological
      confirmation of endometriosis. RESULTS: The majority of patients suspected of
      endometriosis at laparoscopy were confirmed by histological examination, i.e. 138
      out of 164 patients (84.1%). CONCLUSION: Laparoscopy is the easiest diagnostic
      tool for the diagnosis of endometriosis which can be confirmed by histological
      examination.

PMID- 15266762
TI  - Is assisted hatching beneficial in patients with recurrent implantation failures?
AB  - PURPOSE: To assess the possible role of assisted hatching in patients with
      recurrent implantation failure during IVF cycles. DESIGN: Prospective randomized
      study. SETTING: IVF unit of an academic medical center. PATIENTS: Women who
      underwent IVF after at least three failed IVF-ET attempts. INTERVENTIONS:
      Patients were prospectively randomized to undergo assisted hatching of their
      embryos prior to their replacement by mechanical partial zona dissection.
      RESULTS: The study (assisted hatching) and control groups included 104 and 103
      patients, respectively. There were no significant between-group differences in
      patient age, cause of infertility, mean number of previous IVF trials, number of
      oocytes retrieved, fertilization rate, or number of embryos transferred. No
      difference in pregnancy rate was noted on comparison of the whole study group, to
      the whole control group (21% and 27%, respectively). However, when the results
      were re-analyzed by age groups, assisted hatching was found to be harmful in the
      youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs
      35%, p < 0.05). CONCLUSION: Repeated implantation failure alone is not an
      indication for assisted hatching. Although assisted hatching appears to be
      effective in a selected group of older patients, in younger patients it may
      further hamper implantation and should be avoided.

PMID- 15266763
TI  - The importance of diagnostic work-up in the management of candidal
      vulvovaginitis. A prospective study.
AB  - OBJECTIVE: To assess the accuracy of the diagnostic work-up in identifying
      vaginal candidal infection, and to determine the safety, efficacy and speed of
      action of clotrimazole vaginal tablets. PARTICIPANTS: Two hundred and twenty
      three patients with symptoms and signs of candidal infection, a presence of
      vaginal pH < or = 4.5 and positive 10% KOH examination. METHODS: After vaginal
      culture was taken, the eligible patients were treated with clotrimazole 200 mg
      vaginal tabs (manufactured by Teva or Agis). RESULTS: Cultures grew Candida
      albicans in 189 cases (85%), and Candida non-albicans in five (2.2%); 29 patients
      (13%) did not have any candidal infection. Of the 189 C. albicans-positive
      patients, 174 were reassessed for effects of clotrimazole treatment by self
      reports and objective measures. Ninety-four percent of the patients reported
      improvement after treatment, rated moderate to high by 87%. The physician
      evaluation was similar: some improvement in 96%, and moderate or high improvement
      in 91%. At the second examination, 7.5% of the treated patients still had a
      positive culture for Candida albicans, and they remained positive on KOH
      microscopic examination, although vaginal pH was significantly higher. Maximal
      improvement was recorded three to four days after starting treatment. CONCLUSION:
      It is important that the diagnostic work-up for suspected candidal infections
      consist of at least vaginal pH measurement and microscopy study with KOH. We
      encourage the use of vaginal cultures, especially in recurrent cases.
      Clotrimazole is a safe and effective treatment.

PMID- 15266764
TI  - Pharmacological effects of melatonin on reproductive activity: experimental
      bioimplants with sustained-release polymeric systems.
AB  - A vast literature documents the role of melatonin in human reproductive function
      including: a) the relation between melatonin and the menstrual cycle in relation
      to the peak time of luteinizing hormone in the middle of the cycle; b) the
      varying concentrations of melatonin in the control of puberty; c) the fewer
      conceptions in some artic populations where melatonin is connected significantly
      to seasonal photoperiodicity during the months of the polar nights. The aim of
      this paper is to report our findings on the pharmacological action of this
      molecule on reproduction in which gonadal activity is clearly connected to
      photoperiodicity. We used polymer bioimplants programmed for the sustained
      release of melatonin for experimental gynecologic protocols. These implants had
      beneficial results with respect to the use of progestinics because melatonin
      allowed ovarian activity to be induced for at least two to three consecutive
      cycles with one single bioimplant. We thought it indispensable to use
      pharmacological systems with a sustained release because different preliminary
      tests showed that the half-life of melatonin is limited at maximum to two to
      three hours and, consequently, any other tested modalities of administration
      would not provide any appreciable results for our study. As a model for our
      research we used goats to administer melatonin via targeted programs since these
      animals clearly respond (even against the rule of the light/dark relation) in
      contrast to humans in whom response is less evident. For controls, after
      inserting bioimplants in the animals, we tested their efficiency in vitro and
      subsequently in vivo, evaluating blood parameters and pharmacological effects of
      melatonin occurring during the treatment. The final results proved to be
      interesting in relation to reproductive activity in that regular and programmed
      births were achieved.

PMID- 15266765
TI  - Bladder neck mobility and functional evaluation of the pelvic floor in primiparae
      according to the type of delivery.
AB  - In this study, 91 primiparous women were selected, with a period of post-delivery
      variable from 45 to 60 days. These patients were divided according to the type of
      delivery into three groups: I--consisting of 32 patients who had vaginal
      delivery; II--comprised 29 patients who were subjected to forceps; III--formed by
      30 women who were subjected to cesarean section. Patients with a previous
      pregnancy were not included, so that the possible previous alterations of the
      pelvic floor did not interfere with the present evaluation. Patients with a pre
      term pregnancy, fetus below 2,500 g or above 4,000 g, anomalous presentations,
      twin pregnancy, diabetes mellitus, systhemic arterial hypertension, hypertensive
      disease specific of pregnancy, endocrinopathies and neuropathies were also
      excluded. After 45 to 60 days from delivery the patients were subjected to
      anamnesis, gynecological examination, functional evaluation of the pelvic floor
      (FEAF), Q-Tip test and ultrasound of the bladder neck. As for the functional
      evaluation of the pelvic floor, it was observed that the patients with cesarean
      section presented better indexes compared to those who were subjected to forceps.
      The Q-Tip test showed that in both the patients from group I and group II bladder
      neck mobility was greater than in those from group III. Concerning bladder neck
      topography in relation to public symphysis and its mobility, which were evaluated
      by ultrasound, it was observed that at rest all the groups had the neck in a
      supra-pubic position, with no differences among them. Yet, during the required
      strain, the bladder neck stayed in the infra-pubic position with major frequency
      in group I. Bladder neck mobility was greater in the vaginal delivery group in
      relation to the other groups. It was also noticed that the group undergoing
      cesarean section showed less mobility. The obtained results lead us to conclude
      that despite the fact that vaginal delivery may cause displacement of the urethro
      vesical junction during strain, and consequently greater bladder neck mobility,
      it is the attending physician's role to minimize the damage to the pelvic floor,
      thus avoiding the emergence of a predisposing factor to future stress urinary
      incontinence.

PMID- 15266766
TI  - Efficacy and safety of standard versus low-dose Femarelle (DT56a) for the
      treatment of menopausal symptoms.
AB  - OBJECTIVE: In a previous study treatment with a daily standard dose of Femarelle
      (644 mg/day) resulted in a significant elevation in bone mineral density (BMD)
      while a reduced dose resulted in a decrease in BMD. The aim of the current study
      was to examine the efficacy and safety of the two doses of Femarelle in the
      treatment of menopausal symptoms. MATERIALS AND METHODS: Eighty healthy
      postmenopausal women were randomly allocated to receive either the standard dose
      (SD) or low dose (LD) of Femarelle (644 mg/day vs 344 mg/day). A detailed medical
      history was taken on enrollment, followed by a physical examination, pelvic
      ultrasound, and sex hormone and lipid profiles. A detailed Kupperman index for
      each patient was completed. These measures were repeated every three months for
      12 months. RESULTS: In both groups there was a significant reduction in the
      Kupperman index following 12 weeks of treatment, which was sustained throughout
      the 12 months of treatment (p < 0.01). Seventy-six percent of the patients in the
      SD group reported a decrease in vasomotor symptoms and seventy eight % in the LD
      group (NS). This decrease was sustained following 12 months of treatment. There
      was no change in TSH and sex hormone levels or endometrial thickness during the
      study period. CONCLUSIONS: In the current study we found that menopausal symptoms
      were reduced similarly by LD and SD, however for the combined treatment of
      menopausal symptoms and osteoporosis the standard dosage of 644 mg/day of
      Femarelle is needed.

PMID- 15266767
TI  - Age at menarche and risk of abortion: further evidence.
AB  - OBJECTIVES: To study the relationship between the age of menarche and risk of
      abortion. METHODS: Correspondence analysis and application of life table survival
      analysis were used to study the association between the age at menarche and the
      outcome of pregnancy on data collected from 329 women. RESULTS: Both analyses
      showed increased risk of abortion with increasing age of menarche. Risk of
      abortion associated with early age at menarche (9-11 years) was 1.2% and it
      increased to 66.7% when the menarche age was 15 years or above. CONCLUSION: Early
      age at menarche is associated with lower risk of abortion.

PMID- 15266768
TI  - Skeletal maturation in intrauterine growth-retarded rats treated with growth
      hormone.
AB  - The objective of this study was to analyse the effects of intrauterine growth
      retardation (IUGR) and growth hormone (Gh) therapy on skeletal maturation in
      growth retarded rats. One-hundred and thirty-five rats constituted the groups:
      Control (C), Sham-operated (SH), IUGR and IUGR+Gh: injected with Genotropin 3.0
      mg/kg/day) from 21 to 60 days of age. SH was injected only with saline solution.
      The thickness of tibial cartilage was assessed on X-ray at the ages 1, 21, 42, 63
      and 84 days and categorised according to three levels. L1: maximal thickness, L2:
      reduction of 50% and L3: absence. The percentual differences between frequencies
      for each level were compared and clustered by simple ligation in Euclidean
      distance. The results lead to us to conclude that skeletal maturation does not
      appear to be modified by IUGR, while it is accelerated by growth hormone in
      growth-retarded rats.

PMID- 15266769
TI  - Preemptive meloxicam for postoperative pain relief after abdominal hysterectomy.
AB  - OBJECTIVE: This study was conducted to evaluate the analgesic efficacy of
      meloxicam in abdominal hysterectomy. METHODS: The study population consisted of
      52 patients scheduled for total abdominal hysterectomy who were ASA 1 or 2
      physical status female. Patients were allocated randomly to receive orally either
      15 mg of meloxicam (Group M, n = 27) or placebo (Group P, n = 25) before
      anesthesia induction. After intravenous administration of 1.5 mg kg(-1) of
      tramadol, anesthesia was induced with an intravenous loading dose of 1-2 mg kg(
      1) propofol. Anesthesia was maintained on intravenous infusion of propofol at 6
      12 mg kg(-1) h plus tramadol at 1 mg kg(-1) h(-1), vecuronium, and a 2:1 nitrous
      oxide-oxygen mixture. RESULTS: The relative propofol consumption was lower in
      Group M than in Group P, (p < 0.05). The time for analgesic rescue decreased in
      the order Group M > Group P (p < 0.01). The degree of sedation was similar
      between the groups (p > 0.05) and the visual analog scores (10-cm scale) and
      verbal rating scale data differences were present in the first 2 h only (p <
      0.05). When side-effects were evaluated nausea and vomiting were found to be
      lower in group M than in group P (p < 0.05). CONCLUSION: Preemptive meloxicam
      provided better postoperative analgesia than placebo.

PMID- 15266770
TI  - Retrospective analysis of endometrial polyps carried out at Ege University
      Hospital.
AB  - OBJECTIVE: The aim of the present study was to assess the incidence of
      endometrial polyps in women presenting with different symptoms to Ege University
      Hospital. MATERIAL AND METHODS: Patient records were retrospectively scanned and
      patients with a histopathological diagnosis of endometrial polyps were included
      in the analysis. RESULTS: 53 patients had been diagnosed with endometrial polyps.
      Sixty-four percent of the patients were postmenopausal and the most common
      presenting symptom was postmenopausal vaginal bleeding (26.4%). Forty-nine
      percent of the diagnoses were made by endometrial sampling. CONCLUSION: In a
      university hospital setting the majority of the endometrial polyp cases diagnosed
      were in postmenopausal women. Standard endometrial sampling failed to detect
      almost half of the cases.

PMID- 15266771
TI  - Evidence using a shared oocyte pool that the sperm rather than the oocyte in some
      cases may be responsible for the production of embryos with a high percentage of
      fragmented blastomeres--case report.
AB  - PURPOSE: Hypothesis--a sperm defect rather than an oocyte problem may
      occasionally be responsible for blastomere fragmentation. METHODS: The morphology
      of embryos in pairs of women producing embryos from a common pool of oocytes but
      fertilized by two different sperm sources was performed to see if a pair could be
      detected where one woman produced embryos with very little blastomere
      fragmentation vs the other woman having embryos with extensive fragmentation.
      RESULTS: An oocyte donor was identified who produced 49 oocytes resulting in 17
      embryos for the infertile donor to evaluate and 13 for the recipient. Almost all
      of the donor embryos showed extensive fragmentation vs very little for the
      recipient embryos. CONCLUSION: The sperm, in some cases at least, may be the
      etiologic factor for blastomere fragmentation.

PMID- 15266772
TI  - Prenatal diagnosis of pentalogy of Cantrell: a case report.
AB  - Pentalogy of Cantrell is a very rare congenital disorder characterized by ectopia
      cordis in combination with an abdominal wall defect. A case diagnosed prenatally
      at 25 weeks' gestational age is presented.

PMID- 15266773
TI  - Medical and psychological management of recurrent abortion, history of
      postneonatal death, ectopic pregnancy and infertility: successful implementation
      of IVF for multifactorial reproductive dysfunction. A case report.
AB  - The medical and psychological treatment for a 37-year-old Caucasian G6 P1051
      woman who presented for evaluation of secondary infertility and recurrent
      pregnancy loss is described. Although one living child had been conceived without
      medical assistance, that delivery preceded the present evaluation by ten years
      and involved a different partner. With the current husband, the patient had two
      miscarriages and a left ectopic pregnancy. The couple had attempted controlled
      ovarian hyperstimulation and in vitro fertilization (IVF) elsewhere, but the
      cycle was cancelled due to poor follicular response. About one year before
      consultation at our institution, the couple established a pregnancy although the
      infant was born at 24 weeks with a cardiac anomaly, living only 40 days.
      Additionally, a persistent cervical lesion required cone biopsy before any
      fertility treatment could resume. Andrology evaluation found the husband's sperm
      DNA fragmentation index to be 48.6%. This constellation of stressors represented
      substantial emotional issues and psychological therapy/counseling was
      recommended. After obtaining psychological clearance, the couple underwent IVF
      and 16 oocytes were retrieved. Four embryos were transferred, and a healthy male
      infant was delivered at term. Although multifactorial infertility can be
      associated with very poor reproductive outcomes, the advanced reproductive
      technologies merit consideration during management of complex clinical
      challenges. Standard IVF strategies can be optimized by inclusion of thorough
      psychological assessment and counseling.

PMID- 15266774
TI  - Term angular pregnancy with placenta accreta. A case report.
AB  - A 27-year-old primigravida, with two prior adnexal operations, had retained
      placenta with postpartum haemorrhage following an uncomplicated vaginal delivery.
      Laparotomic removal revealed placental accretism. Pharmacological treatment
      (oxytocin and sulprostone) and right cornual resection failed to control profuse
      bleeding. In the end, subtotal hysterectomy was unavoidable.

PMID- 15266775
TI  - Uterine necrosis after laparoscopic uterine vessel dissection for symptomatic
      fibroid--a case report.
AB  - Laparoscopic dissection of uterine vessels is a new minimally invasive method to
      treat symptomatic fibroids. A potential complication of uterine artery dissection
      is uterine necrosis. A woman with a large intramural fibroid underwent
      laparoscopic dissection of the uterine vessels using ultrasonic activated shears
      and three months later developed focal uterine necrosis requiring exploratory
      laparotomy and supracervical hysterectomy. Although uterine artery coagulation
      and dissection are procedures with a low reported rate of complications, uterine
      fibroid or focal uterine necrosis can occur.

PMID- 15266776
TI  - Caudal regression syndrome and sirenomelia in only one twin in two diabetic
      pregnancies.
AB  - Many authors consider sirenomelia to be an extreme form of caudal regression
      syndrome (CRS), while others argue that they are two distinct entities. Maternal
      diabetes mellitus is considered to be an important predisposing factor for both
      CRS and sirenomelia. Two rare cases of diabetic, dizygotic twin pregnancies, each
      with one normal and one affected fetus are presented. In case 1 the affected
      fetus had CRS. In case 2 the affected fetus had sirenomelia. The present cases
      suggest that the pathogenesis of CRS and sirenomelia is more complex than
      previously thought, that maternal diabetes is not the only underlying
      pathogenetic mechanism and that genetic or epigenetic factors probably contribute
      to the formation of these conditions.

PMID- 15266777
TI  - Pelvic actinomycosis in a postmenopausal patient with systemic lupus
      erythematosus mimicking ovarian malignancy: case report and review of the
      literature.
AB  - Pelvic actinomycosis is a chronic granulomatous suppurative disease caused by an
      anaerobic gram-positive organism Actinomyces israelii usually associated with
      intrauterine devices. Systemic lupus erythematosus is an autoimmune disorder
      associated with multiple primary and drug-related immunological defects that
      predispose patients to infections. The combination of both diseases in a
      postmenopausal patient is a rare occurrence. A case of a pelvic mass in a 49-year
      old postmenopausal patient with systemic lupus erythematosus treated with
      immunosuppressive therapy for two years is presented. The patient presented with
      lower abdominal pain to the gynecology clinic and was found to have a pelvic
      tumor. She had no history of intrauterine device use. Histopathologic examination
      of the laparotomy specimen revealed pelvic actinomycosis.

PMID- 15266778
TI  - Nuchal cord type B associated with an excessively long umbilical cord as a cause
      of stillbirth: a case report.
AB  - Nuchal cord (NC) is defined as the umbilical cord being wrapped 360 degrees
      around the fetal neck. It is one of the most common complications of the
      umbilical cord and any pregnancy might be complicated with a nuchal cord. If a
      nuchal cord occurs in a pregnant woman with decreased fetal movements, it should
      be considered to be at high risk, particularly for fetuses with multiple nuchal
      cords. We report a case in breech presentation with an excessively long umbilical
      cord (190 cm) which was complicated with five nuchal loops around the fetal neck
      and resulted in intrauterine death at the 37th week of pregnancy.

PMID- 15266779
TI  - Involvement of somatostatin in breathing control before and after birth, and in
      perinatal and infant sudden unexplained death.
AB  - The distribution of the somatostatin was studied by immunohistochemistry on
      serial sections of the 56 brain stems from subjects aged from 30 gestational
      weeks to 12 postnatal months, dying of both known and unknown causes. The
      unexplained deaths included 13 sudden intrauterine deaths, 4 sudden neonatal
      deaths and 24 sudden infant deaths. We observed intense somatostatin positivity
      in the cell bodies and fibres of many brainstem nuclei prevalently involved in
      the respiratory activity (parabrachial/Kolliker-Fuse complex, locus coeruleus,
      hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus,
      ambiguus nucleus, and reticular formation) in stillbirths. Only in 8 foetuses
      with unexplained death the hypoglossus nucleus was somatostatin-negative. In the
      postnatal deaths, the immunopositivity was prevalently limited to the
      ventrolateral and ventral subnuclei of the tractus solitarii nucleus. In 13
      sudden infant death victims and in one case of death due to pneumonia,
      somatostatin-positivity was also present in the hypoglossus nucleus. We concluded
      that: 1) the somatostatin is an important foetal breathing-inhibitor, but it
      becomes important for the physiological control of respiration immediately after
      delivery; 2) functional alterations of the hypoglossal nucleus can occur in both
      sudden perinatal and infant deaths and contribute to the induction of both fatal
      breathing movements in foetuses and abnormal ventilatory control in infants
      leading to irreversible apneic phenomena.

PMID- 15266780
TI  - The concentration of thyroid hormones and activities of iodothyronine deiodinases
      are altered in human brain gliomas.
AB  - We have determined the cellular concentration of thyroxine (T4) and
      triiodothyronine (T3) and the activities of two brain iodothyronine deiodinases,
      type II (5'-D2) and type III (5-D3), in two types of tissues --tumour (26) and
      non-tumour (5), derived either from human gliomas with various histological
      malignancies or from non-tumoural surrounding brain tissue. As it has been
      established, all patients before the surgery had the Non-Thyroidal Illness
      Syndrome (NTIS). The concentration of serum T3 was therefore significantly
      decreased in all the examined patients. It was over 2.5 times lower than that
      before surgery and 4.0 times lower at surgery than that seen in healthy controls.
      The serum concentration of T4 was found to be below normal range in 4/26 cases
      and in low levels of normal range in 6/26 cases, whereas TSH serum concentration
      in all patients was within normal range. The concentrations of T3 and T4
      (expressed as pg of hormone/mg tissues protein) in 22/26 brain tissue samples
      were significantly lower in gliomas than in 5 non-tumoural brain tissue samples.
      As expected, the alternation in brain 5'D II activity in gliomas was seen in most
      cases with astrocytomas (5/8 cases), gliosarcomas (8/8 cases) and glioblastoma
      multiforme (10/10 cases). In general, the mean enzyme activity in tumour tissue
      was significantly higher than that found in non-tumoural tissue of human brain
      (21.79 fmol of newly generated T3/h/mg of protein vs. 4.88 fmol of T3/h/mg
      protein, respectively). The highest 5'D2 activity with a range from 10.82 to
      45.96 (mean 23.61 fmol T3/h/mg protein) was found in gliosarcomas. The activity
      of 5-D3 was increased (in 8/8 cases of gliosarcoma and in 9/10 cases of
      glioblastoma multiforme) or decreased (in 3/3 cases of astrocytoma II, 5/5 cases
      of astrocytoma III) when compared to mean activity of this enzyme found in non
      tumoural brain tissue. In summary, our results suggest that the concentration of
      brain iodothyronines and metabolism of thyroid hormones in the examined human
      brain tumours are altered. These changes may be related to malignant progression.

PMID- 15266781
TI  - Remote morphological changes in the white matter after ischaemic stroke.
AB  - Acute phase of stroke is the focus of most experimental and clinical studies on
      cerebral ischaemia. The scarcity of data on remote changes led us to examine the
      morphological pictures of brains after ischaemic insults. We paid special
      attention to the white matter capillaries. We microscopically evaluated 10 brains
      of patients who died after one month to fourteen years after the ischaemic
      stroke. Morphological examinations involved the application of routine
      histological stains and immunohistochemical reactions with antibodies against
      human albumin, GFAP, macrophage antigen CD 68 and lectins (Ulex europaeus, Wheat
      Germ agglutinin and Bandeirea simplicifolia). The results showed a swelling of
      the endothelial cells and their invagination into the vessel lumen.
      Postapoplectic cavities and white matter spongiosis decreasing with increase in
      distance from the cavity were observed. Immunohistochemical study showed that
      there was no segmental immunoreactivity to lectins on the capillary wall. Immune
      reaction to albumin revealed protein extravasation to the rarefied brain
      parenchyma. Our results indicate that progressing damage of the white matter
      after ischaemia may be caused not only by degeneration of axons of neurones
      destroyed by stroke, but also by pathological changes in small blood vessels,
      especially in capillaries. Hence, vascular leukoencephalopathy is probably caused
      by arteriolar damage as well as by microangiopathy.

PMID- 15266782
TI  - Ultrastructural evaluation of activated forms of microglia in human brain in
      selected neurological diseases (SSPE, Wilson's disease and Alzheimer's disease).
AB  - Activated forms of microglia were ultrastructurally evaluated in three
      neurological diseases of different aetiology (subacute sclerosing panencephalitis
      -SSPE, Wilson's disease and Alzheimer's disease). The occurrence of activated
      rod, ramified and amoeboid microglia was found in the investigated diseases. The
      widest ultrastructural variability of microglia was in SSPE, including the
      presence of mitotic chromosomes or centrioles in its cytoplasm, which indicates
      microglia proliferation. In the nuclei of activated microglia, some nuclear
      bodies with different structures were frequently seen, whereas lamellar
      structures (similar to developing Birbeck's bodies--pathognomonic to Langerhans
      type dendritic cells) were observed in the cytoplasm. The activated forms of
      microglia with apoptotic features were found only in SSPE cases. Some apoptotic
      nuclei were filled with nucleocapsids of measles virus. In Alzheimer's disease,
      activated microglia was most frequently bound to senile plaques. Ramified
      microglia was in contact with amyloid fibrils, which penetrated its cytoplasm and
      reached the nuclear membrane and channels of rough endoplasmic reticulum, or was
      situated among dystrophic neurites. Rod microglia was found predominantly at the
      edge of senile plaques. In Wilson's disease, the ultrastructure of activated
      microglia showed mostly indirect forms between rod, ramified and amoeboid
      microglia. The microglia ultrastructure suggests that its morphological form may
      express functional involvement in the pathogenesis of a given disease entity.

PMID- 15266783
TI  - Influence of small mechanical head injuries on peripheral blood natural killer
      cytotoxicity (NKCC) in rats.
AB  - Many neurophysiological experiments and some human's brain tissue stimulatory
      therapies require surgery intervention, which results in small mechanical skull
      and brain tissue injuries. Additionally, these procedures need some local or
      short general anaesthesia, which is not neutral for immune system action.
      Clinical data unambiguously shows that severe head and brain injuries and
      anaesthesia can suppress immunity. The aim of the present study was to
      investigate the influence of small mechanical skull and brain tissue injuries,
      accompanied by electrode fixation for experimental or therapeutic brain tissue
      stimulation, on peripheral blood natural killer cytotoxicity (NKCC) assessed in a
      4h standard cytotoxic test. Additionally, we assessed a number of leukocytes,
      lymphocytes and large granular lymphocytes (LGL), which are NK cell subset and
      plasma corticosterone concentration. The results showed that small mechanical
      skull and meninges injuries or alone-administered Nembutal did not evoke any
      significant changes as those caused by electrode placement 4.2 mm below the skull
      surface. Deeper electrode fixation, 6.1; 7.6 and 8.4 mm below the skull surface,
      significantly increased NKCC (p < 0.05) and LGL number (p < 0.05) on the 3rd day
      after the electrode placement. Moreover, the results showed that some small brain
      tissue injuries could transiently influence the number of LGL and NKCC.

PMID- 15266784
TI  - Fate of myelinated fibres in the optic nerves in experimental Creutzfeldt-Jakob
      disease in rodents: an ultrastructural study.
AB  - We report the ultrastructural appearances of myelinated fibres of the optic
      nerves from mice infected with the Fujisaki strain of Gerstmann-Straussler
      Scheinker (GSS) disease and from Echigo-1 strain of Creutzfeldt-Jakob disease
      (CJD). Optic nerves from CJD- and GSS-infected rodents showed severe pathological
      changes. Theses changes were qualitatively indistinguishable from each other but
      were more robust in the Fujisaki GSS model than in the hamsters inoculated with
      Echigo-1. The most characteristic finding was the distension with the attenuation
      of the myelin sheath forming a vacuole while shrunken axon was attached to the
      innermost layer of the myelin. With high power electron microscopy, we could
      observe the splitting of the myelin lamellae at the major dense or intraperiod
      lines to form complex openings that extended to line the vacuole. This finding
      suggests that myelin lamellae participate in the formation of vacuoles.

PMID- 15266785
TI  - Matrix metalloproteases activity and ultrastructural changes in the early phase
      of experimental allergic encephalomyelitis. The effect of oral treatment with
      spinal cord hydrolysate [correction of hydrolisate] proteins in Lewis rat. The
      pilot study.
AB  - Matrix metalloproteinases (MMPs) are a family of genes of the neutral proteinases
      that are important to normal development and to a variety of pathological
      processes including neuroinflammation. In the central nervous system (CNS), MMPs
      degrade components of the basal lamina, leading to disruption of the blood-brain
      barrier (BBB), and contribute to the neuroinflammatory responses. Their
      concentration in experimental allergic encephalomyelitis (EAE) increases a few
      folds and is accompanied by a thinner basal membrane in the early phase of EAE.
      After induction of oral tolerance by pretreatment with spinal cord hydrolisate
      proteins, the concentration of MMPs decreased by 30%. Other ultrastructural
      changes were observed in the early phase of EAE, i.e., karioskeletal damage with
      vesicular structures in karioplasm, compartmentalisation of the endoplasmic
      reticulum in perikarium, large cisterns of the Golgi apparatus, increased
      activity of microglial cells with numbers of phagolisosomes, disorganisation of
      sheets of myelin, neoangiogenesis in parenchyma of the cerebral cortex. After
      oral pretreatment with spinal cord hydrolisate proteins, no changes in
      karioskeletal proteins were found. Still Golgi apparatus spheres were large. Many
      pores in the nuclear membranes were observed, which is probably a sign of
      increased genetic information transport. We also observed some collagen fibrils
      as a sign of reparative processes. These results show the diminishing of
      inflammation in the early phase of EAE after oral induction of immunological
      tolerance and some possibilities of clinical implication in multiple sclerosis
      treatment.

PMID- 15266786
TI  - Hyperglycaemia and intramitochondrial glycogen granules in the brain of mice.
      Ultrastructural study.
AB  - The mechanism of cytotoxic effects of hyperglycaemia on the brain has not yet
      been explained and the proposed hypotheses are not fully convincing. In the
      present study, we aimed to assess the effect of high doses of glucose on the
      ultrastructure of the mice brain. The results, which are in agreement with the
      literature data, show that the administration of a single high dose of glucose,
      as well as its chronic application, leads to accumulation of glycogen granules in
      the cytoplasm of astrocytes. A new observation is the detection of glycogen
      granules in the ultrastructurally changed mitochondria of astrocytes as well as
      in the mitochondria of some synapses. Our hypothesis assumes that excess of
      glucose may cause an increase in the vulnerability of the brain mitochondria.
      This in turn may enable glucose and cytoplasmic enzymes to penetrate into the
      mitochondria and they therein synthesise glycogen. Mitochondrial dysfunction may
      in turn lead to neurodegeneration by apoptotic process.

PMID- 15266787
TI  - Progressive supranuclear palsy--parkinsonian disorder with tau pathology.
AB  - Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski
      syndrome, is a rare form of parkinsonism characterised by abundant tau pathology.
      Only a few familial cases have been reported, therefore PSP can be considered as
      a sporadic tauopathy. Recent case-control studies of patients with sporadic PSP
      suggest that PSP has a recessive pattern of inheritance. Strong genetic evidences
      for the involvement of the tau gene variability in the pathogenesis of PSP have
      been demonstrated in several Caucasian populations. We review the most important
      DNA polymorphisms (e.g.: A0 polymorphism and H1 haplotype) contributing to the
      risk of PSP. Moreover, we discuss how these DNA polymorphisms may influence the
      exon 10 splicing, and thus the proportion of 4R/3R tau isoforms, leading to a
      class II tau pathology in PSP patients.

PMID- 15266788
TI  - [Growth and survival of seeds of the oyster Crassostrea virginica in a shrimp
      farm in Yucatan, Mexico].
AB  - A lot of 1600 seeds of American oyster Crassostrea virginica from the coastal
      lagoon La Redonda, Tabasco, Mexico was cultured in main drainage channel (S1), a
      secondary drainage channel (S2), the floodgate of a white shrimp Pennaeus
      vannamei pond (S3) and the marine water supply pond (S4). The seeds, with a total
      height and initial humid weight of 31.67 +/- 3.43 mm and 4.29 +/- 1.32 g,
      respectively, were cultured in suspended Nestier oyster boxes at 575 org/m2.
      Biological and environmental parameters were recorded after 296 days, the seeds
      in S4 reached height and weight values of 52.55 +/- 7.51 mm and 16.30 +/- 4.94 g,
      respectively. The index of physiologic condition along the experiment had a
      variation of 1.26% to 3.45%. In S4 the survival was 81.0%. In the other places
      the mortality was total after 90 days.

PMID- 15266789
TI  - [Reef community structure at Falcon, Venezuela, before and after a mass
      mortality].
AB  - Morrocoy National Park used to be considered the most important continental coral
      reef of Venezuela. However, in January of 1996, there was a massive mortality of
      the benthic organisms for unknown reasons. The coral reef community was monitored
      since 1995, the year before the event, and yearly after that, until June 1999, by
      sampling linear transects and quadrats. A total of 26 hard corals were recorded
      in the study site (Playa Mero) in 1995 (36.56% cover), which already had some
      deterioration because 90.86% of the living coral cover was represented basically
      by four species, M. annularis with 51.36%, Colpophyllia natans with 18.22%,
      Agaricia agaricites with 11.58% and Porites porites with 9.70%. Three months
      after the event, living coral cover was only 4.84% and algae, particularly
      Dyctiota spp. covered most of the surface (81.89%). Benthic organisms suffered
      massive mortality over the whole depth gradient and in most park reefs. Even
      after three years the reef community shows highly perturbed conditions, with 85%
      of the total cover represented by the categories: dead coral, dead coral
      overgrowth by algae and sand. From the initial coral richness of the area (26
      species) only nine species were observed although in very low cover (<1%), except
      for M. annularis and M. franksi, which presented lightly higher percentages.

PMID- 15266790
TI  - [In vitro effect of an alkaloid isolated from Amphimedon viridis (Porifea) on
      promastigots of Leishmania mexicana].
AB  - The dose dependent antiproliferative effect of an alkaloidal substance extracted
      from the sponge Amphimedon viridis was tested on Leishmania mexicana
      promastigotes. Sponges were collected in Isla Larga, Venezuela (10 degrees 20'
      20" - 10 degrees 24" N, 64 degrees 19' - 64 degrees 22' W), cut and dipped in
      methanol for vacum filtering extraction every 24 hr. The aqueous extract was
      separated by chromatography over silica gel. The parasites were from the
      Venezuelan NR strain. Their growth rate was reduced by 50 % with a dose of 10
      microg/ml in 48 hr, whilst concentrations of 30 and 40 microg/ml induce
      leishmanicidal action after 110 and 20 min, respectively. Lysis is preceded by an
      immediate increase in cellular volume associated with progressive damage of
      cellular content and the destruction of organelles. These findings suggest that
      one important factor associated with the antiproliferative effect of this
      alkaloidal substance on L. mexicana promastigotes is the loss of the plasma
      membrane selective permeability.

PMID- 15266791
TI  - [Environmental evaluation near a fuel vendor within Parque Nacional Morrocoy,
      Venezuela. II: Water quality, sediments and biota].
AB  - This paper is the second part of a base line study carried out in the coastal
      region near a marine service station located in Morrocoy National Park,
      Venezuela. Results from a physical and chemical characterization of the water and
      sediments of four sites located around the service station are presented. The
      physical and chemical factors measured in water included: temperature, salinity,
      specific conductance, dissolved oxygen, saturation percentage of dissolved
      oxygen, pH, total suspended solids, transparency, oil and grease, total residual
      petroleum hydrocarbon, vanadium and lead, total coliform bacteria, and the
      presence of coliform bacteria. The factors measured in sediments include:
      granulometry, organic material, total carbonates, vanadium, lead, oil and grease,
      and total hydrocarbons. In addition, the amount of vanadium and lead in sample
      tissue from three species which are abundant and widely distributed in each site
      was measured in order to evaluate the potential of these species as bio
      indicators. The water in the area where this study was conducted is shallow,
      warm, and thermally homogeneous, with high salinity and normal pH and dissolved
      oxygen, and supersaturated with oxygen in certain hours in sites adjacent to
      abundant underwater vegetation. The water is moderately turbid with a tendency
      towards less dissolved oxygen with increased depth. The estimated values of
      NMP/100 ml of the coliform fecal organisms is within legal limits even though the
      total number of water coliforms measured in Site 2 was ten times higher than in
      Site 1. This increase is associated with the proximity of Site 2 to an outflow of
      pre-treated sewage. The values of TRPH in the water collected from each site were
      low and very close to the detection limit (0.8/ml). Vanadium was not found, while
      lead was detected in 11 of the 12 samples. Compared to the values measured for
      Site 1, which was the local reference, only one sample had a concentration of
      three times the maximum baseline. The amount of lead found in all analyzed
      samples was acceptable, according to the standards set by the State of Washington
      (maximum value: 292 mg/kg), while the concentration of lead in the sediments
      around the supply dock were 1.5 to 3.4 times greater than the Dutch norm. It can
      be concluded that there is no evidence of an accumulation of Va or Pb in the
      species selected as bioindicators. An observation program is proposed in which
      variables similar to those measured for this characterization will be studied
      with some modifications. A more intense sampling of some variables is recommended
      (lead in water and sediments, total coliform and fecal matter in consecutive
      samples and in days following a high concentration of visitors) as is the
      elimination or minimization of other variables.

PMID- 15266792
TI  - [Distribution, abundance, density and morphometry of Strombus gigas
      (Mesogasteropoda: Strombidae) in Alacranes reef, Yucatan, Mexico].
AB  - A population of the conch Strombus gigas was sampled in 109 transects (100 x 10 m
      each) for an area of 109000 m2 (eight surveys in 1998 and six in 1999) in
      Yucatan, Mexico; S. gigas was the most abundant conch species (97% of
      individuals) and ocurred at depths of 0.5-18 m. Mean density was 0.0084
      individuals/m2 (Standard deviation SD=0.0138, n=1910). Maximum density (0.015
      individuals/m2) was at 0.5-2 m and minimal (0.001 individuals/m2) at 16-18 m.
      Shell length was 120-290 mm (mena=211.6, SD=26, n=1136). Shell lip thickness,
      measured only in adults, was 1-28 mm (mean=8.7, SD=7.5, n=1136).

PMID- 15266793
TI  - [Embrionary development of Strombus pugilis (Mesogastropoda: Strombidae) in the
      laboratory].
AB  - Stages from oviposition to veliger hatching are described for Strombus pugilis
      under laboratory conditions. Two egg masses from Playa Seyba, Mexico, (20 degrees
      45' N, 91 degrees 45' W) were used (three sub-samples per mass). Each sub-sample
      was immersed in a 11 container at 29 +/- 1 degrees C. This description is based
      on stages known from Strombus gigas, which include number of: fertilized eggs,
      morulae, gastrulae, trochophore larvae with slow movements, larvae with
      primordium foot, larvae with eyes, larvae with statocyst and veliger larvae. Eggs
      with first division appeared five hours after oviposition in the three replicates
      of each mass, although in greatest number in one of the egg masses. Trochophore
      larvae with slow movements appear after 50-54 hours and veligers hatch after 90
      hours.

PMID- 15266794
TI  - [Somatic production of two species: Crassostrea virginica and Ischadium recurvum
      Bivalvia in Mecoacan, Tabasco, Mexico].
AB  - The Mexican oyster fishery, 90% supported by the coastal lagoons of the Gulf of
      Mexico, has decreased drastically in the last six years as a result of
      anthropogenic pollution and improper management. The mussel Ischadium recurvum
      has proliferated and competes with oysters for space and probably food.
      Crassostrea virginica and Ischadium recurvum were studied to evaluate somatic
      production with biometry and physiological condition indices (PCI's) during an
      annual cycle. A random sample of 200 organisms was taken montly for each species.
      Condition indices wet flesh weigth: wet shell weight ratio (WFW/WSW), dry flesh
      weight: wet flesh weight ratio (DFW/WFW), dry flesh wet: dry shell weight ratio
      (DFW/DSW), and ash free dry weight: tissue dry weight (AFDW/TDW) were calculated.
      In order to stablish physiological condition and temporal variability, these
      indices were compared between species and months. The somatic production of
      mussels was higher than in oysters. This enhancement in production could be
      explained by: 1) Mussel uses less energy for shell production, 2) a constant
      recruitment of mussel almost year-round, and 3) the mesohalin lagoon was more
      favourable to the mussel.

PMID- 15266795
TI  - [Reproductive cycle and index of condition used for Melongena corona (Mollusca:
      Gastropoda)].
AB  - Melongena corona bispinosa was studied in Yucatan, Mexico (21 degrees 16' N, 89
      degrees 49' W) for a year. Males have reproductive peaks in February and
      December, and a post-copulation peak in June. Female peaks are in March and May,
      plus oviposition peaks in April and January. Males and females differ in the mean
      gonadosom ic index (F=13.79, p<0.05) but not in the dry tissue/shell weight
      (F=0.0902, p<0.05), dry tissue and total weight (F=0.2466, p<0.05) and dry tissue
      weight/internal shell volume (F=1.0565, p<0.05).

PMID- 15266796
TI  - [Ingestion and digestion of seven species of microalgae by larvae of Strombus
      gigas (Mesogastropoda: Strombidae)].
AB  - The potential nutritional value of seven microalgal diets as measured by their
      ingestibility and digestibility to queen conch Strombus gigas larvae was tested
      with 30 day old larvae reared at 28 degrees C and fed at 1000 cells x ml(-1). The
      algae were Tetraselmis suecica, Tetraselmis chuii Isochrysis aff. galbana,
      Dunaliella tertiolecta, Chlamydomonas coccoides, Chaetoceros sp. and
      Thalassiosira fluviatilis. Ingestion and digestion were measured by the four
      nutritional stages studied with epifluorescence microscopy with live larvae.
      Temporal and absolute indices showed that larvae fed Chaetoceros sp. and T.
      fluviatilis had lower ingestion and digestion levels. The other algae are
      recommend to feed S. gigas larvae.

PMID- 15266797
TI  - User perceptions on coastal resource state and management options in Curacao.
AB  - Public environmental awareness and support for management measures are key
      determinants of the scope for successful implementation of natural resource
      management. To assess user perceptions and opinions on resource state and
      potential management options for the coastal zone of Curacao, we queried 250
      coastal resource users from around the island (sport divers, part-time artisanal
      fishermen and recreational boaters) using questionnaires. There is wide awareness
      of a long-term decline in coastal resource condition as measured by various
      indicators. Even among fishermen there was wide awareness of anthropogenic
      contributors to the decline, broad agreement of management measures required and
      a general willingness to contribute to management by means of annual license
      fees. Some of the more salient findings include the endorsement by fishermen of
      the current ban on spearfishing (81%), the regulation of the beach seine fishery
      for scad (77%), the introduction of fish reserves (72%), special protection for
      sea turtles (90%), conch (82%), and lobsters (72%), and notable support for
      gradual elimination of trap fisheries (45%). Also, both divers (65%) and boaters
      (92%) expressed the importance to them of an attractive coastline, with both
      groups expressing preference for natural (un-built) coastline (>74%) above other
      categories. Management based on the concept "user pays", as already implemented
      in the Netherlands Antilles on Saba and Bonaire, is well supported by the
      resource user public. A review of other main constraints such as finances and
      institutional capacity, shows that conditions are quite favorable for
      implementation of new legislation. Modem coral reef management is urgently needed
      in Curacao to safeguard a key natural resource and concerted action is called for
      on the part of government agencies, legislators and elected officials.

PMID- 15266798
TI  - [Reef fishes community structure of Playa Mero, Parque Nacional Morrocoy,
      Venezuela].
AB  - The coral reef fish community was studied in Playa Mero, Morrocoy National Park,
      after the mass mortality of January, 1996 with a systematic sampling design.
      Transects and quadrates were used for corals, and a visual census for fishes. The
      coral community is highly disturbed with extensive areas of dead coral covered by
      algae, and low coverage and richness of coral species, gorgonians, sponges and
      briozooans. These factors have generated a relatively homogeneous environment
      with respect to the fish community, which was dominated by Scaridae and
      Pomacentridae that represented 75% of fish. Dominant fishes were mainly
      herbivorous (75.4% of all fish) apparently because of the disturbance that caused
      the settling of algae.

PMID- 15266799
TI  - Distribution of the cyanophyte Trichodesmium (Oscillatoriaceae) in the eastern
      Caribbean Sea: influence of the Orinoco River.
AB  - Orinoco River influence in the Caribbean Sea, characterized by high nutrient
      input, causes a decrease of Trichodesmium populations. The Caribbean Time Series
      (CaTS) station, south of Puerto Rico (17 degrees 36'N 67 degrees 00'W), was
      monitored for 25 months in order to observe the Trichodesmium abundance pattern
      and the presence of the river plume. In general, mean Trichodesmium abundance was
      higher at the surface and decreased with depth. The mean upper water column
      (surface to 20 m) abundance was 54.1 +/- 32.6 col/m3. Within the sampling period,
      abundance was highly variable (1-700 col/m3). Correlation between Trichodesmium
      abundance and wind speed (p=0.002), chlorophyll a concentration (p=0.001),
      nitrate (p=0.02) and silicate (p=0.003) concentrations were statistically
      significant. However, Trichodesmium abundance was not correlated with salinity
      (p=0.70), temperature (p=0.16) and seawater density (p=0.71) variations at CaTS.
      Eastern Caribbean regions highly influenced by the Orinoco River discharge were
      devoid of Trichodesmium colonies.

PMID- 15266800
TI  - [Abundance of Lytechinus variegatus (Echinoidea: Toxopneustidae) in the island of
      Cubagua, Venezuela].
AB  - The sea urchin roe is among the highest valued seafood items in the world.
      Increasing demand has extended this fishery worldwide and cases of overfishing
      have been detected in some countries. On the eastern coast of Venezuela some
      species of sea urchin, such as Lytechinus variegatus, are consumed as food but
      studies to determine the abundance and size do no exist. Between February 1998
      and April 1999 six sampling stations (depth under 5 m) in Cubagua island
      (perimeter 25 km) were visited in 11 occasions to study the population density of
      L. variegatus, with a 0.25 m2 quadrat thrown eight times over seagrass (Thalassia
      testudinum) beds. Temperature was determined on site, and water samples for
      salinity and dissolved oxygen concentration were collected. Each specimen was
      measured and returned to the sea. Diameter range was 8.6 to 74.2 mm (n=3 404) and
      mean size 26.56-55.34 mm. On the northern coast density varied from 2 to 23
      urchins/m2; on the eastern coast from 15 to 82/m2 and from 21 to 58/m2 on the
      southern coast. On the north coast the seagrass beds are scarce.

PMID- 15266801
TI  - [Structure and dynamics of the community associated to cultivated Gracilariopsis
      tenuifrons (Gracilariacea) in Chacopata, Sucre, Venezuela. I: Faunistic
      inventory].
AB  - The associated fauna of Gracilariopsis tenuifrons (Gracilariaceae, Rhodophyta)
      cultures was collected between October 1994 and December 1996 in Chacopata (Sucre
      State, Venezuela) and preserved in 10% formaldehyde. The species list includes 17
      Crustacea, 14 Mollusca and six Polychaeta, the remaining taxa added ten species
      (total 47 species in eight Phyla). Grazing by mesoherbivores affected the algae
      and the mollusk Aplysia protea damaged new cultures significantly. The abundance
      of tubes built by the amphipod Euricthonius brasiliensis impairs algal aspect and
      facilitates colonization by other organisms.

PMID- 15266802
TI  - [Eclossion of cysts of two species of Dendrocephalus (Anostraca:
      Thamnocephalidae) of potential use as food in aquaculture].
AB  - The use of Artemia salina nauplii as live food has significantly aided culture of
      commercial fish and shrimps in recent years. However, reported deficiencies in
      the nutritional value of some strains originated the study of freshwater fairy
      shrimps as an alternative to Artemia. This study presents cyst biometry for
      Dendrocephalus geayi and D. spartaenovae (Anostraca: Thamnocephalidae), and the
      effects of some physicochemical variables on cyst hatching. The biometric
      characteristics of D. geayi and D. spartaenovae are within the size range of
      commercial Artemia strains. Favorable conditions to hatch D. geayi are 30 degrees
      C and conductivity near that of distilled water (<5 micromhos). For D.
      spartaenovae, these conditions are 28 degrees C and 280 micromhos. A very low
      salinity such as 1 per thousand inhibits hatching in both species.

PMID- 15266803
TI  - [Availabilty of juveniles from natural sources of the oyster Pteria colymbus
      (Bivalvia: Mytilidae), in the Gulf of Cariaco, Venezuela].
AB  - We examined the spat availability the oyster Pteria colymbus at 6-8 and 19-21 m
      depths for 15 months (March 1993-June 1994) in Turpialito, Golfo de Cariaco,
      Venezuela. Spats were trapped using artificial collectors (plastic filaments in
      bags, 30 x 60 mm), suspended from a long line. Each collector was replaced by a
      replica monthly to analyse abundance, shell dimension and mass of P. colymbus.
      Intraweekly, the temperature, salinity, oxygen and food availability (Chlorophyll
      a, total seston, organic and inorganic seston) were determinated. There is
      juvenile recruitment all year, suggesting continuous reproduction. Spat counts
      were higher at 6-8 m (generally 50-230 juveniles per collector) with peaks in
      August and December 1993 (April and June 93 at 19-21 m). The length-weigh mass
      relation was higher at 19-21 m, suggesting greater food availability because of
      lower organism density (including P. colymbus) and a greater water flux.
      Phytoplanktonic abundance and temperature were correlated (r2=0.38) with juvenile
      abundanc; this relationship and the association of juvenile abundance with higher
      temperature and Chlorophyll a levels, suggest that spat abundance was higher at
      the beginning of the water stratification period, when phytoplankton biomass is
      high.

PMID- 15266804
TI  - [Effects of acclimation temperature on the growth of Perna viridis (Bivalvia:
      Mytilidae), using the RNA/DNA ratio].
AB  - Temperature affects growth rate in aquatic organisms. This can be evaluated in
      short term using biochemical indexes (RNA/DNA and Protein/DNA). The effect of
      acclimatization temperature on the instantaneous growth and physiological
      condition of Perna viridis was studied in organisms collected in La Esmeralda,
      Sucre State (Venezuela) and taken to the laboratory, where groups of 100
      organisms (size 3.0 - 3.5 cm, anteroposterior measurement) were acclimatized at
      15, 20, 26 or 28 degrees C during four weeks. Later they were kept in a 60 liters
      aquarium for another six weeks under the same conditions. Each week, ten
      organisms per group were extracted to measure concentrations of RNA, DNA (by a
      fluorometric method with ethidium bromide) and proteins (by a colorimetric
      method), in tissues (digestive gland, adductor muscle and gills). Protein
      concentration was greater and highly significant at 15 degrees C for all studied
      tissues. The opposite was obtained with the RNA/DNA and Protein/DNA ratios: the
      greatest increase was observed at the highest temperature (28 degrees C) for all
      tissues. At the lowest temperature there was a tendency to reduce both indexes
      with time. Greater instantaneous growth can be expected at higher temperatures
      and 28 degrees C was optimal for growth in these specimens.

PMID- 15266805
TI  - [Food effect on the physiological condition of the mussel Perna viridis
      (Bivalvia: Mytilidae), using the RNA/DNA ratio].
AB  - The green mussel, Perna viridis, became widespread in the northern coast of Sucre
      State since its arrival to Venezuela in 1993. RNA/DNA and Protein/DNA ratios were
      used to study the effect of starvation on its instantaneous growth. The mussels
      were collected in La Esmeralda and Chacopata, acclimatized in the laboratory for
      four weeks and maintained for another six weeks in two groups: one fed ad libitum
      and another without food (this later group was later fed for two additional
      weeks). Protein (colorimetric method), and nucleic acid concentrations (RNA and
      DNA, fluorometric method with ethidium bromide) were measured in adductor muscle,
      digestive gland and gills. The instantaneous growth was assessed using RNA/DNA
      and Protein/DNA rations. These indexes were always higher in the fed organisms.
      Animals from Chacopata were in better physiological condition that those from La
      Esmeralda during the abstinence time (six weeks). Muscle was the best tissue to
      determine instantaneous growth. The RNA/DNA ratio is a reliable index to
      determine the physiological condition and instantaneous growth of this species.

PMID- 15266806
TI  - [Verification of the eclossion mark on the sagittal otolith of the larvae of
      Sardinella aurita (Pisces: Clupeidae)].
AB  - The study of otolith in larvae is important to determine fish age and growth,
      essential parameters in the study and management of fisheries resources. In this
      study, the formation of the hatching mark in Sardinella aurita was verified on
      ichthyoplankton samples collected off southern Cubagua island, Venezuela, from
      May 1998 to January 1999. The embryos were kept alive using a culture system
      until they hatched and daily a group of 10 to 30 larvae were fixed in 95%
      ethanol. An image analysis system was used to measure morphometric
      characteristics of larvae and sagittal otoliths. Following are mean values in
      newly hatched larvae: otolith hatching mark distance from nucleus 4.78 m (I.C.
      0.36 m, p 0.05 n = 30), increase width 1.46 m (I.C. 0.17 microm, p 0.05, n = 30)
      and diameter 14.28 m (IC 1.11 m, p 0.05, n = 30). The mean standard length of
      larvae at age 0 was 3.31 mm (I.C. 0.08 mm, p 0.05, n = 200). The identification
      of the hatching mark allows the exact calculation of the number of rings in
      larvae from the natural environment.

PMID- 15266807
TI  - Polymorphisms of octopine dehydrogenase (Odh) in mollusks and implications for
      the neutralism-selectionism hypothesis.
AB  - Octopine dehydrogenase (Odh) was examined in several species of bivalves and
      gastropods and complemented with bibliographic data, to assess the controversy
      between neutralism and selectionism in explaining the maintenance of genetic
      variation in natural populations. This debate was the center of the molecular
      evolution and population genetic research in the 1970s and 1980s, but waned
      thereafter, without resolution. Although DNA data have been produced,
      implications are not understood. We examined the polymorphims of Odh in several
      species of bivalves and gastropods, and the kinetic properties (apparent Km) of
      the different isozymes in the scallop Euvola ziczac that indicates an apparent
      case of overdominance of the heterozygous individuals. The question "which of the
      two hypothesis is correct" has shifted with time to "how much influence did each
      factor have in the maintenance of genetic variation".

PMID- 15266808
TI  - [Physical properties of the agar of Gracilariopsis tenuifrons (Gracilariacea)
      from Sucre, Venezuela].
AB  - The yield, gel strength, gelling and melting temperatures of Gracilariopsis
      tenuifrons agar from Guayacan, Araya Peninsula, Sucre State, Venezuela were
      determined. Yield values with and without alkali treatment ranged from 23.22 to
      39.57% and from 16.29 to 22.42% respectively, while gel strength with alkali
      treatment fluctuated betwen 699.31 and 1231.69 g/cm2 and without treatment varied
      from 278.0 to 691.06 g/cm2. Gelling and melting temperatures were in the range
      reported for other agarophytes. Considering gel strength, the agar quality of G.
      tenuifrons was higher than in other species and its exploitation in economically
      feasible.

PMID- 15266809
TI  - [Antimicrobial activity of organic extracts isolated from Aplysina fistularis
      (Demospongiae: Aplysinidae)].
AB  - Organic extracts of the sponge Aplysina fistularis (Pallas 1766) were tested for
      antimicrobial activity against Gram positive bacteria (Staphylococcus aureus) and
      Gram negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas
      aeruginosa). The minimal inhibitory concentration (MIC) and toxic activity of
      extract were determined. Susceptibility trials of organic fractions obtained by
      VLC: Hexane, EtOAc and CHCl3 showed that EtOAc fraction has antibacterial
      activity against E. coli, while CHCl3 fraction inhibited E. coli and S. aureus
      growth. The later refractioning of EtOAc fraction and the biodirected assays
      showed that fractions F12 and F13 of EtOAc/Hex and EtOAc F14 were bioactive
      against Gram positive and Gram negative bacteria. Only EtOAc/MeOH Sf2 from
      subfractionig of EtOAc F14 produced inhibition for E. coli and S. aureus. In Sf2
      EtOAc/MeOH, MIC was moderate for S. aureus (MIC > 256 g/ml). F4 CHCl3/MeOH
      produced a high inhibition in S. aureus (MIC = 0.125 g/ml) and for E. coli (MIC >
      16 g/ml). F10 CHCl3/MeOH showed a moderate activity against S. aureus (MIC > 128
      g/ml) and low activity against E. coli (MIC = 512 g/ml). F10 CHCL3/MeOH did no
      present toxic activity against Artemia salina. The fractiorts F4 CHCL3/MeOH and
      Sf2 EtOAc/MeOH were toxic for this organism when the concentration was higher
      than 100 microg/ml. LC50 in both cases was 548.4 and 243.4 microg/ml
      respectively. Secondary metabolites of medium polarity obtained from A.
      fistularis have a wide spectrum of anti bacterial activity. Toxicity analysis
      suggests that only F10 CHCL3/MeOH has potential as an antimicrobial agent for
      clinical use.

PMID- 15266810
TI  - [Iron and copper in Plagioscion squamosissimus (Piscis: Sciaenidae) from the
      Orinoco river, Venezuela].
AB  - Bauxite explotation of the Orinoco River in recent years is an important source
      of heavy metals discharge in the ecosystem, changing the natural biochemical flow
      of these elements and their concentrations in water, sediment and organisms. Iron
      and copper concentrations were measured in the fish Plagioscion squamosissimus in
      the Orinoco river, by sampling the fish population for three months (September
      November 1998) in the main channel of the middle Orinoco (07 degrees 38' 21.2" N;
      66 degrees 19' 10.9" W) and in Castillero lagoon (7 degrees 39' 09" N; 66 degrees
      09' 00" W) with 2 and 4 cm mesh sizes. The internal organs of 30 fishes per month
      and site were stove-dried at 80 degrees C, pulverized and dried in disecator for
      30 min to use as indicators with the acid digestion method for predicting the
      effect of heavy metals. We found relatively high values of iron and copper
      concentrations in fishes of the lagoon, and high seasonal variations in the iron
      concentration.

PMID- 15266811
TI  - [Kinetic incorporation of mercury in Emerita portoricensis (Crustacea:
      Decapoda)].
AB  - Benthic test species used in toxicity assays are the best indicators of sediment
      toxicity because they live in direct contact with sediments and the water column.
      Mercury chloride is one the most toxic metallic salts. Its strong affinity for
      particles explains the high Hg content found in benthic populations. The genus
      Emerita is abundantly found in Venezuelan coasts and is a good bioaccumulator of
      pollutants, but the toxicological assays performend on this genus are scarce. The
      present experimental test reports on the distribution of mercury in the water
      column and sediment, using static bioassay in short term (24 hr) and the ability
      of Emerita portoricensis to bioconcentrate mercury under experimental conditions.
      Our results suggest that the Hg transference from water to sediment is enhanced
      in the presence of Emerita. The kinetic uptake of Hg in Emerita portoricensis
      shows a mechanism of rapid absorption reaching high metal concentrations in short
      exposure times.

PMID- 15266812
TI  - [Cooper, cadmium and lead in the fish Cyprinodon dearborni, in the sediments and
      in the water of two lagoons in Venezuela].
AB  - The concentration of copper, cadmium and lead in superficial sediment, water and
      the fish Cyprinodon dearborni was determined in two coastal lagoons of Sucre
      State, Venezuela. Chacopata lagoon is hyper saline while Los Patos lagoon is hypo
      saline and receives significant wastewater from Cumana city. Water, sediment and
      fish samples were collected in February 1998. In the laboratory, samples
      underwent acid digestion and were analyzed by atomic absorption spectophotometry.
      The mean values of the metals in C. dearborni from the Chacopata lagoon were:
      159.26 +/- 210.68 microg/g for Cu, 44.71 +/- 45.58 microg/g for Cd, and 9.31 +/-
      23.34 microg/g for Pb, while for Los Patos lagoon the mean values were: 64.88 +/-
      16.30, 19.48 +/- 5.81 and 22.85 +/- 20.00, respectively. In the water column, the
      metal concentration ranges were: 2.3-11.6, 3.9-5.4 and 21-32 mg/l for copper,
      cadmium and lead, respectively. These results suggest that metal levels in
      sediment, water column and organisms in both lagoons do not differ, except for
      lead, even though only Los Patos receives waste water.

PMID- 15266813
TI  - [Benthic macrofauna associated to Thalassia testudinum in Bahia de Mochima,
      Sucre, Venezuela].
AB  - Diversity and abundance of benthic macrofauna associated to Thalassia testudinum
      were studied at Ensenada de Reyes, Mochima Bay, in the northeastern coast of
      Venezuela. Samples were taken monthly in six stations, three at 1 m in depth and
      three at 6 m, between December 1992 and February 1994, using a quadrat of 0.25 m2
      for collecting plants and sediment; each sample was washed with seawater through
      a 1 mm sieve. The specimens were fixed in 6% formaldehyde. A total of 1722
      organisms (6 888 ind x m2) and 127 species of macroinvertebrates were collected.
      Mollusks dominated with 53 species, followed by polychaetes (40), crustaceans
      (18) and echinoderms (8). Remaining groups were represented by 1-2 species. The
      highest abundance was in October (214 specimens), and the lowest in December 1993
      (79 specimens). Specific richness was between 47 species in October and 18 in May
      1993. Mean species diversity was 2.79-1.36 bits/ind. There were differences
      (ANOVA p<0.01) in number of specimens at the two depths but not throughout the 15
      month study period (p>0.05). There were more specimens and species at the lowest
      depth and in stations with higher Thalassia testudinum biomass.

PMID- 15266814
TI  - [Benthic fauna associated to a Thalassia testudinum (Hydrocharitaceae) bed in
      Parque Nacional Morrocoy, Venezuela].
AB  - The benthic fauna and diel variation in a shallow seagrass bed (Thalassia
      testudinum) were studied in Playa Mero, Venezuela. Samples of organisms and
      sediments were taken using PVC cylinders, 5cm in diameter, along a transect
      perpendicular to the coast. Seagrass cover, shoot density and biomass were
      estimated. The seagrass cover was homogeneous along the transect. The
      intermediate zone had the highest number of shoots and of above-ground and
      rhizome biomass. Composition and abundance of benthic organisms were related with
      seagrass and sediment characteristics. Sediment organic matter content and
      organism abundance were highest near the shore Molluscs, polychaetes,
      oligochaetes and nematodes were the most abundant groups. Species richness was
      higher in daytime (40 versus 28 at night). Gastropods were the most abundant
      organisms both at day and night while polychaetes and crustaceans increased
      during the day, and holoturids were more numerous at night.

PMID- 15266815
TI  - [Effects of hyposalinity in Thalassia testudinum (Hydrocharitaceae) from Parque
      Nacional Morrocoy, Venezuela].
AB  - The year 1996 had a high pluviosity in Morrocoy National Park (western coastal
      zone, Venezuela) and low salinity in December 1996 affected the seagrass beds,
      dominated by Thalassia testudinum. Patches without T. testudinum were observed in
      localities of the park that used to have very dense populations of this plant.
      Sampling was done at Las Luisas to determine leaf productivity, turnover rate,
      short shoot density and relative biomass of plant sections, in order to compare
      with data obtained in September 1996, previous to the event. Green leaves, roots
      and rhizomes were the most affected parts. Mean green leaf biomass decreased in
      January and February 1997 to 5% of the plant's total biomass; mean root biomass
      decreased in March to 40% and mean rhi zome biomass decreased in February to 30%.
      The density of the active short shoots decreased to a minimum in February, but in
      April it reached a value similar to that of September 1996. The density of the
      inactive short shoots decreased to a minimum in March, and they dissappeared in
      April, matching the increasing density of the active short shoots between these
      two months. In February 1997, 56% of the inactive short shoots showed evidence of
      leaf initiation. In January 1997 the leaf productivity and turnover rate values
      (2.72 +/- 0.35 g/m2/d and 2.15% leaf DW/d) were similar to the annual mean
      previously determined from Las Luisas (2.35 +/- 0.72 g/m2/d and 1.96% leaf DW/d).
      Nevertheless, the values of productivity and turnover rate detected at Las Luisas
      in April 1997 (4.88 +/- 2.14 g/m2/d and 4.66% leaf DW/d) were higher than those
      values previously reported for this location. In response to the mortality
      episode, the leaf productivity and turnover rate of T. testudinum increased and
      the leaf initiation was activated in the inactive short shoots.

PMID- 15266816
TI  - [Nitrogen, phosphorus and the C/N ratio in superficial sediments of the lagoon of
      Chacopata, Sucre, Venezuela].
AB  - The basal behaviour and relationship with organic carbon (Corg) content and
      prevailing granulometric fractions, of organic nitrogen (Norg), total phosphorus
      (P-total) and C/N ratio in surface sediments of Chacopata lagoon, Sucre State,
      Venezuela, were studied. Concentrations and spatial gradients were determined in
      sixteen stations following a common method for marine sediments. Norg
      concentrations varied between 0.102 and 0.510% (x = 0.237%), total phosphorus
      between 0.012 and 0.094% (x = 0.058%) and C/N ratio between 9.27 and 44.47 (x =
      20.53). The higher contents of Norg and total phosphorus are from sections with
      an abundance of mangroves, marine phanerogams, macroalgae, benthonic biomass and
      migratory birds shelters. The C/N ratio shows the typical values for carbonated
      sediments, indicating that the nitrogenous compounds are rapidly degraded and the
      organic matter presents itself as humic substances. This parameter was moderately
      associated with silt and clay, and showed antagonism with sand, whereas Norg and
      phosphorus showed no correlation with them. The organic contribution is purely
      autochthonous: no anthropogenous contributions were found.

PMID- 15266817
TI  - [I Guidelines from the Cardiology-Geriatrics Study Group of the Sociedade
      Brasileira de Cardiologia].

PMID- 15266818
TI  - [Review of the II Guidelines of the Sociedade Brasileira de Cardiologia for the
      diagnosis and treatment of heart failure].

PMID- 15266819
TI  - [Inspiration from diffuse panbronchiolitis].
AB  - Diffuse panbronchiolitis is a new respiratory tract disease and was initially
      found in Japan. Strong association between race-dependent antigens and diffuse
      panbronchiolitis suggests a genetic predisposition to the disease. 14-member ring
      and 15-member ring macrolides have been proved to have significant therapeutical
      effect on diffuse panbronchiolitis. The discovery of diffuse panbronchiolitis and
      the advent of macrolide therapy for this disease suggests that clinicians should
      pay more attention to racial difference of some diseases and never overlook any
      accidental phenomenon in clinical practice.

PMID- 15266820
TI  - [Comparison of unfractionated heparin and low molecular weight heparin in
      pulmonary thromboembolism: meta-analysis].
AB  - OBJECTIVE: To pool the data of studies about anticoagulation in non-massive
      pulmonary thromboembolism (PTE) and evaluate the efficacy and safety of low
      molecular weight heparin (LMWH) and unfractionated heparin (UFH) as the initial
      treatment. METHODS: MEDLINE CD-ROM from January 1966 to August 2003 and CBM CD
      ROM from January 1978 to August 2003 were chosen for searching the randomized
      clinical trials (RCTs) that compared the efficacy or safety of LMWH and UFH in
      non-massive PTE. A meta-analysis was employed to evaluate the results of these
      two therapies. RESULTS: Five RCTs including 999 cases were analyzed. Compared
      with UFH, the combined odds ratio (OR) of LMWH in treating PTE was as follows:
      (1) The total OR of mortality of PTE patients treated with LMWH was 0.81 (95%CI
      0.36-1.81, P > 0.05); (2) The total OR of recurrence of venous thromboembolism
      (VTE) in PTE patients treated with LMWH was 0.37 (95%CI 0.14-1.00, P=0.05); (3)
      The total OR of bleeding in LMWH was 0.47 (95%CI 0.16-1.39, P > 0.05);(4) The
      total OR of heparin-induced thrombocytopenia (HIT) in LMWH was 0.66 (95%CI 0.06
      6.92, P > 0.05). CONCLUSIONS: LMWH and UFH can reduce the mortality and
      recurrence of VTE in patients with PTE in the same degree. The risk of major
      bleeding was similar in the two treatment groups. Initial subcutaneous therapy
      with the LMWH appeared to be as effective and safe as intravenous UFH in the
      initial treatment of PTE.

PMID- 15266821
TI  - [Inhibition of human lung fibroblast proliferation and the mitogen activated
      protein kinase pathway by dexamethasone].
AB  - OBJECTIVE: To investigate the effects of dexamethasone on human lung fibroblast
      cell proliferation, cell cycles, and cell mitogen-activated protein kinases
      (MAPKs) passway. METHODS: Dexamethasone was used at various concentration in
      culture medium. Cell number was counted using a hemacytometer. Whole cell
      propidium iodide staining and flow cytometric analysis were performed to
      determine cellular DNA content. MAPK proteins and activation were tested by
      Western blot analysis with antibodies to c-Jun N-terminal kinase (JNK), phospho
      JNK, extracellular signal-regulated kinase (ERK), phospho-ERK, p38 and phospho
      p38. RESULTS: 1x10(-7) mol/L and 1x10(-6) mol/L dexamethasone suppressed the
      proliferation of lung fibroblast cells by 34% and 72%, respectively, than that of
      control. This suppression was dose-dependant. Dexamethasone suppressed cell cycle
      with accumulation of cells in G1/G0 stage. It increased from 81.9% to 90.1%
      compared with that of control. We did not find any apoptosis induced by
      dexamethasone for lung fibroblast cells. Using Western blot analysis, we found
      that dexamethasone resulted in decreased activity of ERK, but had no effects on
      JNK and p38. CONCLUSIONS: Dexamethasone may suppresses the proliferation of lung
      fibroblast cells, which is partly resulted from the facts that it can inhibit ERK
      activation in MAPK-signaling pathway but has little effect on JNK and p38
      pathway. Dexamethasone may not induce lung fibroblast cell apoptosis directly.

PMID- 15266822
TI  - [Influence of different sleep stages on respiratory regulation in normal humans].
AB  - OBJECTIVE: To understand the influence of different sleep stages on respiratory
      regulation in normal people. METHODS: We measured ventilation (VE) and occlusion
      pressure (P0.1) responses to hyperoxia hypercapnia (deltaVE/deltaPaCO2,
      deltaP0.1/deltaPaCO2) and isocapnic hypoxia (deltaVE/deltaSaO2 and
      deltaP0.1/deltaSaO2) in eleven non-snoring healthy people during wakefulness and
      during non-rapid eye movement (NREM) I + II, NREM III+IV, and rapid eye movement
      (REM) sleep stages. RESULTS: During NREM I + II and NREM III+IV, the normal
      subjects showed no significant decrease in P0.1, deltaP0.1/deltaSaO2 and
      deltaP0.1/deltaPaCO2 (P > 0.05), but deltaVE/ deltaSaO2 and deltaVE/ deltaPaCO2
      decreased significantly (P < 0.05). During REM sleep, P0.1 maintained the level
      during wakefulness, but both hypoxic and hypercapnic responses decreased
      significantly (P < 0.05). CONCLUSIONS: Sleep has significant influence on
      respiratory regulation in normal people. The respiratory drive (P0.1) in both
      NREM and REM sleep stages could maintain the awake level due to an effective
      compensation to the increase of upper airway resistance. The P0.1 responses to
      both hypoxia and hypercapnia decrease only in REM sleep stage, which is in
      consistent with the clinical phenomenon that sleep disordered breathing occurs in
      REM in normal people.

PMID- 15266823
TI  - [Quantitative structural study of pulmonary artery in patients with pulmonary
      atresia with ventricular septal defect ].
AB  - OBJECTIVE: In order to provide pathologic reference for therapeutic rationale,
      the pathological changes of the pulmonary vasculature in patients with pulmonary
      atresia with ventricular defect and patent ductus arteriosus were observed by
      contrast with normal control group. METHODS: Lung biopsies were taken in the
      operation in 10 children suffered from pulmonary atresia with ventricular septal
      defect associated with patent ductus arteriosus (PA group). Autopsy specimens
      were obtained from 10 children died of non-cardiovascular diseases as normal
      control group. The tissue was fixed with buffered formalin, routinely prepared by
      impregnated in wax. Sections were stained by hematoxylin-eosin, Weigert's elastic
      stain counter-stained by van Gieoson's method. Seven parameters were obtained
      including percentage of media thickness (MT%), percentage of media section area
      (MS%), numbers of vascular per square centimeter (VPSC), mean alveolar number
      (MAN), mean linear intercept (MLI), proportion of parenchyma area in total area
      (PPA), and alveolar/vascular ratio per unit area (AVR) by a computer image
      processor by quantitative analysis. RESULTS: There were significant difference
      between the two groups in MAN, VPSC, and AVR (P < 0.05). VPSC was significantly
      lower in PA group than in control group (P < 0.01). Other parameters had no
      significant difference. The mean alveolar diameter had an increased trend in PA
      group, although there was no significant difference. MS% of nearly 50% patients
      was closed to the normal value in PA group. The shape of pulmonary arteriole was
      irregular. There were few muscular arteries in a field of vision. CONCLUSIONS:
      The density of muscular arteries decreases in patients with pulmonary atresia
      with ventricular septal defect and patent ductus arteriosus, but percentage of
      media thickness and percentage of media section area of pulmonary arterioles are
      close to the normal value. Diminished flow in pulmonary circulation has a
      significant effect on numbers of pulmonary arterioles per square centimeter that
      impact the selection of surgical method and the effect of operation because of
      the reduction pulmonary arterioles. The decrease of mean alveolar number results
      in compensatory enlargement of alveolar diameter. The impaired lung development
      is a major cause of abnormal lung function. Feasible and earlier operation, which
      can increase pulmonary flow and promote development of pulmonary vasculature will
      be helpful to restore lung function.

PMID- 15266824
TI  - [Relationship between epidemiological evidence and fatality rate in patients with
      severe acute respiratory syndrome].
AB  - OBJECTIVE: To investgate the relationship between epidemiological diagnosis and
      fatality rate in patients with severe acute respiratory syndrome (SARS). METHODS:
      Epidemiological evidences and the outcomes of 304 patients with confirmed SARS
      were retrospectively analyzed. Patients included highly contagious cases, cluster
      cases, and sporadic cases. RESULTS: The case fatality rate was 8.2%. The fatality
      rate had a tendency of increase in an order of sporadic cases, cluster cases, and
      highly contagious cases (3.9%, 11.4%, and 17.2%, respectively, chi2trend=7.561, P
      < 0.01). Chi square-test also proved that the fatality rate was higher in older
      people (chi2trend=27.024, P < 0.01) and in male (male vs female: 12.2% vs 5.5%).
      A logistic regression model showed that the epidemiological evidence, age, and
      gender were correlated to fatality rate. By observing changes of the odds ratio
      for epidemic evidence, age, and gender using forward method, we found epidemic
      evidence was an independent risk factor related to fatality rate in SARS
      patients. CONCLUSION: The epidemiological evidence is an independent factor
      related to fatality rate in SARS patients. Highly contagious case has a worse
      prognosis and higher fatality rate than sporadic cases and cluster cases.

PMID- 15266825
TI  - [Quantitative detection of SARS-CoV RNA in excreta and oropharyngeal washing
      fluid from convalescence patients with severe acute respiratory syndrome].
AB  - OBJECTIVE: To detect the severe acute respiratory syndrome coronavirus (SARS-CoV)
      RNA in excreta and oropharyngeal washing fluid (OWF) from the convalescence SARS
      patients, and to determine whether convalescence patients carry the SARS-CoV, and
      whether having infectivity. METHODS: Totally 531 samples (including urine, stool,
      and OWF) were collected from 177 convalescence patients with positive SARS
      antibody which were confirmed by ELISA method. Real-time quantitative PCR was
      performed to detect the RNA of the SARS-CoV, and results were analyzed by SPSS
      analysis software. RESULTS: There were 49 (27.7%) cases of SARS-CoV RNA detection
      positive in 177 patients, including 31 (17.5%) cases with one sample positive, 14
      (7.9%) cases with two samples positive, and 4 (2.3%) cases with three samples
      positive. The positive rates of urine, stool, and OWF were 14.7% (26/177), 11.9%
      (21/177), and 13.6% (24/177), respectively. The quantity of SARS-CoV RNA in
      samples was 100-47 000 copies/ml. No significant difference was found among
      urine, stool, and OWF on the difference grade quantity of SARS-CoV RNA quantity.
      CONCLUSIONS: About 10% convalescence SARS patients might still carry the SARS-CoV
      in hospitalization. The detection of SARS-CoV RNA by real-time quantitative PCR
      may become a laboratory examination warranty for convalescence SARS patients to
      discharge hospital and relieve separation.

PMID- 15266827
TI  - [Morphological characteristics of Plasmodium yoelii schizonts in ghost
      erythrocytes].
AB  - OBJECTIVE: To observe the morphological characteristics of Plasmodium yoelii
      schizogony in their ghost erythrocytes. METHODS: Saponify, hypotonic shock, and
      electron microscopy were used to observe the different fashions of erythrocytic
      parasites and their characteristic organellae in ghost erythrocytes. RESULTS: The
      malarial parasites and their fine structures were dramatically well preserved in
      the ghost erythrocytes, such as the ring-like early trophozoites, the brassiere
      like early schizonts, the emerging buds on the surface of late schizonts, and the
      grape-cluster like late schizonts. The cytostome, food vacuole, and crystallized
      malarial pigments were found in the early trophozoites. The proliferations of
      nucleoplasma and nuclear membrane as well as and the clot-like nuclear division
      were followed by the budding during the schizogony. CONCLUSION: The saponify
      technique that makes the erythrocytic malaria parasites and their fine organellae
      to be dramatically revealed in their ghost erythrocytes, may be a useful method
      in the Plasmodium biological research and anti-malaria immunological researches.

PMID- 15266826
TI  - [Mechanism of interleukin-1beta increasing growth hormone expression in rat
      pituitary GH3 cells].
AB  - OBJECTIVE: To investigate the effect(s) of interleukin-1beta (IL-1beta) on the
      activity of human growth hormone (hGH) gene promoter in rat pituitary GH3 cells
      and the molecular mechanism. METHODS: The method of luciferase reporter gene was
      used. We firstly established stable GH3 cell line which contains hGH gene
      promoter -484-30 bp and luciferase reporter gene. After treating these cells with
      IL-1beta or IL-1beta plus various signaling transduction inhibitors, the
      concentration of GH in the medium and lysate of GH3 cells and luciferase
      activities in GH3 cells were measured to reflect the effect of IL-1beta on
      secretion and synthesis of GH and the promoter activity of the hGH gene and the
      molecular mechanism. Results IL-1beta (10-10(4)U/ml) increased secretion and
      synthesis of GH. IL-1beta at levels of 10(2)-10(4) U/ml promoted the luciferase
      expression in stable GH3 cells, and the maximal action was 1.61 times of the
      control (P < 0.001). Among the inhibitors of intracellular signaling transduction
      pathways, mitogen-activated protein kinases (MAPK) inhibitor PD98059 (40
      micromol/L) and p38 MAPK inhibitor SB203580 (5 micromol/L) completely blocked the
      stimulatory effect of IL-1beta, and phosphoinositide 3-kinase (PI3-K) inhibitor
      LY294002 (10 micromol/L) partly blocked the induction of IL-1beta. Neither
      overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1beta
      induction of hGH promoter activity. The stimulatory effect of IL-1beta was
      abolished following deletion of the -196 to -132 bp fragment. CONCLUSIONS: IL
      1beta increases the activity of hGH gene promoter in rat pituitary GH3 cells.
      This stimulatory effect of IL-1beta appears to require the intracellular MAPK,
      p38 MAPK, and PI3-K dependent signaling pathways. The effect of IL-1beta requires
      the promoter sequence that spans the -196 to -132 bp fragment of the gene, but it
      is unrelated to Pit-1 protein.

PMID- 15266828
TI  - [Non cholangio-contrast cholangiopancreatography using multi-slice spiral CT].
AB  - OBJECTIVE: To investigate the feasibility of multi-slice spiral CT (MSCT) for
      cholangiopancreatography without cholangio-contrast. METHODS: Ten patients
      without any digestion system diseases and 24 patients with suspected pancreatic
      malignancy received the 16-slice spiral CT multi-phased contrast-enhanced
      scanning. The images of patients without any digestion system diseases and cancer
      suffered patients were curved reformatted (CR) technique to perform the structure
      of pancreatic duct, common bile duct, and ampulla. The cholangiopancreatical
      systems of the cancer suffered patient were reconstructed through volume
      rendering technique (VRT), minimum intensity projection (MinIP), and indirect
      minimum intensity projection (IMinIP). The results of patients without any
      digestion system diseases in curved multiplanar reconstruction were analyzed;
      meanwhile display rates of the pancreatic duct, common bile duct, and ampulla
      were evaluated. RESULTS: of the four different cholangiopancreatographies were
      compared. RESULTS: The display rate of pancreatic duct in the CR images was 90.0
      (9/10) with an average diameter of (2.63 +/- 0.51) mm. Sub-pancreatic duct could
      be seen in 88.9% (8/9) of them. The display rate of common bile duct in the CR
      images was 100% (10/10) with an average diameter of (7.45 +/- 1.12) mm. The
      display rate of ampulla was 60.0 (6/10), which was affected by the filling status
      of duodenum. The cholangiopancreatography using CR, VRT, MinIP, and IMinIP for
      patients with pancreatic cancer reveal the whole pancreatic and common bile duct,
      and the modality of distal obstructed bile duct. The result showed that IminIP
      got the best outcome (98.6%), while VRT got the worst (68.1%). CONCLUSION: The
      negative CT cholangiopancreatography is a simple and non-invasive examination. It
      reflects both the 3-dimensional cholangio-pancreatic anatomical structure and its
      adjacent condition. It has curtain clinical application values, especially for
      patients with obstructed duct system.

PMID- 15266829
TI  - [Effect of BMP-7 on the transdifferentiation of cultured human tubular epithelial
      cell induced by TGF-beta1].
AB  - OBJECTIVE: To observe the effect of bone morphogenetic protein-7 (BMP-7) on the
      transdifferentiation of cultured human tubular epithelial cell (HKC) induced by
      TGF-beta1 and to elucidate its possible mechanism. METHODS: The cultured HKC
      cells were divided into 5 groups: serum-free group (negative control); single TGF
      beta1 treated group (positive control); single BMP-7 treated group; combined TGF
      beta1 and BMP-7 treated group; and BMP-7 pre-treated group. Expression of keratin
      of HKC cells was assessed by indirect enzyme immunohistochemistry (IEI),
      expression of alpha-smooth muscle actin (alpha-SMA) and E-cadherin by
      immunohistological method, percentage of alpha-SMA positive HKC cells by flow
      cytometry, and mRNA expression of alpha-SMA, TGF-beta1, and TGF-beta type II
      receptor by reverse transcription PCR. RESULTS: The expression of alpha-SMA and
      the percentage of alpha-SMA positive HKC cells markedly increased after having
      been treated by TGF-beta1 while the expression of E-cadherin and keratin
      decreased. In the group pre-treated with BMP-7 (50 ng/ml) and then added with TGF
      beta1 (8 ng/ml), expression of alpha-SMA was significantly lower than in the
      positive control group, while expression of E-cadherin and keratin significantly
      higher than in the positive control group. Measurement of the percentage of alpha
      SMA positive HKC found significant deference between the combined TGF-beta1 and
      BMP-7 treated group and the positive control group (9.7% vs 19.8%; 5.8% vs 19.8%;
      P < 0.05). Significant difference existed between the BMP-7 (50 ng/ml) pre
      treated group and the positive control group (8.7% vs 19.8%, P < 0.05). mRNA
      expression of alpha-SMA was measured by RT-PCR and the results showed that it
      significantly decreased in the group treated or pre-treated with BMP-7 (50 ng/ml)
      (15% and 12% of the results in the positive control group, respectively). The
      mRNA expression levels of both TGF-beta1 and its type II receptor significantly
      decreased (28% and 19%; 47% and 36%, compared with the positive control group,
      respectively). CONCLUSION: Transdifferentiation of cultured renal epithelial cell
      induced by TGF-beta1 can be inhibittd by certain levels of BMP-7, cultured
      together with TGF-beta1 or pretreated. BMP-7 can prevent and inhibit the mRNA
      expression of TGF-beta1 and its type II receptor, which may be an important
      mechanism by which BMP-7 inhibit the transdifferentiation of renal tubular
      epithelial cell.

PMID- 15266831
TI  - [Clinical features of ventilator-associated pneumonia caused by acinetobacter].
AB  - OBJECTIVE: To investigate the clinical features of ventilator-associated
      pneumonia (VAP) caused by acinetobacter. METHODS: The clinical manifestations of
      45 cases with ventilator-associated pneumonia caused by acinetobacter between
      1995 and 2002 were analyzed. Bacterial susceptibility of acinetobacter strains
      was determined by Kerby-Bauer method. RESULTS: The mean age of the subjects was
      58 +/- 13 years with 31 patients older than 60 years. All the patients had
      underlying diseases, most of which were respiratory diseases (37.8%), nervous
      system diseases (22.2%), and trauma (22.2%). Thirteen cases (28.9%) were mixed
      infections with other bacteria. The main manifestations were fever, purulent
      secretion, and solidification in the lung. X-ray revealed inflammatory
      infiltration in lower lobes of both sides. The mortality was 37.8%. The in vitro
      activity tests of 28 antibiotics against the acinetobacter strains showed that
      they were multiresistant. Polymysin B, imipenem, minocycline, ofloxacin, and
      amikacin were relatively active. CONCLUSION: The patients with VAP caused by
      acinetobacter usually had underlying diseases without unique features and high
      mortality, and the isolated strains were often mutiresistant. It is necessary to
      make early diagnosis, select the appropriate agents, and improve the disinfection
      of the breath loop in the ventilator.

PMID- 15266830
TI  - [Protective and therapeutic effect of pulmonary surfactant on the experimental
      chronic obstructive pulmonary disease in hamsters].
AB  - OBJECTIVE: To investigate the protective and therapeutic effects of pulmonary
      surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in
      hamsters. METHODS: COPD animal model was established by smoke inhalations and
      intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters
      were divided into 9 groups as follows: normal group (N), two groups received
      smoke inhalations for 1 and 3 months (S1 and S3), one group received
      intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month
      smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months
      of smoking (SP3), and two groups received intratracheal administration of
      elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively
      (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0,
      1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3).
      EP1 group were killed at the first month, and EP3 at the third month. Light
      microscopy and electromicroscopy observations were performed in each group.
      Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary
      alveolar area (PAA) was measured by image analysis. The expression of surfactant
      protein A (SP-A) were observed by immunohistochemistry. RESULTS: Smoking for 3
      months and instillations of elastase resulted in chronic bronchitis and
      emphysema. MLI and PAA increased and MAN decreased in all the experimental groups
      compared with in the normal group (P < 0.05 or P < 0.01). Administration of
      surfactant for 3 months resulted in statistically significant inhibition of
      pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in
      S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the
      type II alveolar epithelia decreased in S3 and E3 (compared with the normal group
      P < 0.01). After pulmonary surfactant intervention, the expression of SP-A
      increased significantly. CONCLUSION: Pulmonary surfactant may have a long-term
      protective effect on chronic smoking and elastase-induced COPD.

PMID- 15266832
TI  - [Efficacy and safety of arbidol in treatment of naturally acquired influenza].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Arbidol in the treatment of
      naturally acquired influenza. METHODS: A randomized, double-blinded, placebo
      controlled trial was conducted. Subjects were enrolled. The inclusion criteria
      included: aged 18 to 65 years, presented within 36 hours of onset of influenza
      symptoms; and had documented temperature of 37.8 degrees C or higher during an
      influenza outbreak in the community. Individuals were randomly divided Arbidol
      group (200 mg three times daily for 5 days) or placebo group. RESULTS: Totally
      232 individuals were recruited and received medication and follow-up. All of them
      were qualified to be analyzed for safety as intent-to-treat population (ITT) (113
      Arbidol, 109 placebo). Twenty-two (9.48%) were during follow-up or refused to
      continue the trial, and 210 completed as schecule and identified as PP population
      (102 Arbidol, 108 placebo). Totally 125 individuals were identified as influenza
      infected through laboratory test, which was defined as PPi population (59
      Arbidol, 66 placebo). In PPi population, the cumulative alleviation proportion of
      Arbidol group was significantly higher than that of placebo group. The median
      duration of illness was 72.0 hours (95% confident interval (CI) 66.00-78.00
      hours) in Arbidol group and 96.0 hours (95% CI 87.46-104.54 hours) in placebo
      group. The median area under the curve (AUC) of decreased total score were
      significantly higher in Arbidol group than in placebo group, which were 780.00
      and 684.00 score-hours respectively. For PP population, similar results were
      seen. Adverse events reported were similar in Arbidol group and in placebo group.
      The main adverse events were gastrointestial symptoms and increased transaminase.
      CONCLUSION: Arbidol was effective and well tolerated in the treatment of early
      naturally acquired influenza.

PMID- 15266833
TI  - [Dystrophin and utrophin expression in muscle tissues of DMD mouse model after
      transplantation treatment by bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To observe dystrophin and utrophin expression in muscle tissues of
      Duchenne muscular dystrophy (DMD) mouse model (dko mouse) after having been
      treated with bone marrow mesenchymal stem cells (MSC) transplantation. METHODS:
      The fifth generation of MSCs, cultured in vitro, was transplanted into dko mice
      by tail vein. The fluorescent expression of dystrophin and utrophin in
      gastrocnemius muscle tissue of dko mouse was detected and the average optical
      density of positive fibers was calculated. RESULTS: MSCs that had been cultured
      for three generations had good homogeneousness and the immunological reaction
      after vein transplantation was low. There was an increasing tendency of
      dystrophin and utrophin fluorescent expression in sarcolemma of dko mouse within
      5-20 weeks. Significant difference existed in fluorescent average optical density
      of positive fibers fifteen weeks before and after cell transplantation.
      CONCLUSIONS: MSC has strong plasticity both in vitro and in vivo. MSC has a trend
      to reach the injured muscle tissues and turn into muscle fibers, which express
      dystrophin and utrophin. There is some plerosis function for myatrophy of dko
      mouse by MSC transplantation.

PMID- 15266834
TI  - [Detection of eotaxin and its clinical diagnosis value in patients with bronchial
      asthma].
AB  - OBJECTIVE: To explore the role of eotaxin in the pathogenesis of bronchial asthma
      and the clinical value in the diagnosis of asthma. METHODS: Serum eotaxin were
      measured by ELISA in 38 patients with asthma, 28 patients with non-asthma
      allergy, and 30 healthy controls. RESULTS: The levels of serum eotaxin in the
      asthma group were higher than those in the non-asthma allergic and control group
      (P<0.01). Furthermore, eotaxin levels in patients with acute asthma were
      significantly higher than those in patients with stable asthma (P<0.001). It was
      also found that the eotaxin levels of the acute asthma group were positively
      correlated to the amounts of eosinophils in peripheral blood (r=0.4196, P<0.001),
      and inversely correlated to the forced expiratory volume in one second (FEV1) (r=
      0.3746, P<0.001). CONCLUSION: It suggests that eotaxin may play a crucial
      pathogenic role in the asthmatic process possibly by activating the allergic
      inflammatory cells and controlling the recruitment of eosinophils from blood to
      bronchial epithelium of the airway. The concentration of eotaxin is significantly
      associated with the attack of acute asthma and its severity. Eotaxin may be a
      potential therapeutic target in patients with asthma.

PMID- 15266835
TI  - [Effect of exogenous pulmonary surfactant on isolated lung injury induced by
      ischemia-reperfusion in rats].
AB  - OBJECTIVE: To study the effect of exogenous pulmonary surfactant (PS) on the
      acute lung injury to ischemia-reperfusion injury. METHODS: The model of ischemia
      reperfusion was established. Thirty male Sprague-Dawley rats were randomly
      divided into control (n = 10), I/R (n = 10), and PS (n = 10) groups. CONTROL
      GROUP: the isolated rat lungs were reperfused for 4 hours. I/R group: the
      isolated rat lungs were reperfused for 2 hours after 2 hours ischemia. PS group:
      exogenous pulmonary surfactant (10 mg/100 g BW) were given to the ischemic lungs
      through bronchus 2 hours before reperfusion. Wet to dry lung weight ratio (W/D)
      and pulmonary artery pressure (PAP) were checked. Immunohistochemical technique
      was used to determine the immune reactivity of lung tissues to endothelia nitric
      oxide synthase (eNOS) and surfactant protein A (SP-A). The pulmonary changes were
      also observed by light and electronic microscopes. RESULTS: W/D and PAP in I/R
      group were significantly higher than in PS group (P < 0.01). The expression of
      eNOS and SP-A in I/R group were significantly lower than those in PS group (P <
      0.05). CONCLUSIONS: PS can significantly protect lung injury induced by ischemia
      reperfusion in the isolated rat lungs. This protective effect is associated with
      the mechanism that the exogenous PS may reduce SP-A loss in the ischemia
      reperfusion and activate the up-regulation of eNOS.

PMID- 15266836
TI  - [Clinical analysis of lymphangioleiomyomatosis].
AB  - OBJECTIVE: To improve the diagnosis and treatment of lymphangioleiomyomatosis
      (LAM). METHODS: The clinical data of four cases of lymphangioleiomyomatosis
      diagnosed in our hospital were analyzed and corresponding literature was
      reviewed. RESULTS: Lymphangioleiomyomatosis, a rare disorder of unknown cause
      that occured almost exclusively in women of child bearing ages, was characterized
      microscopically by atypical smooth muscle proliferation. It could occur as a
      sporadic diseases or as a part of tuberous sclerosis complex (TSC). LAM was
      associated with progressive dyspnea, recurrent spontaneous pneumothoraces,
      chylous effusions, and hamartomas. CONCLUSION: Clinicians should be familiar with
      the characteristics of LAM so that diagnosis and treatment can be made earlier to
      improve the prognosis.

PMID- 15266837
TI  - [Diagnosis and surgical treatment of solid-pseudopapillary tumor of the
      pancreas].
AB  - OBJECTIVE: To study the diagnosis and treatment of solid-pseudopapillary tumor of
      the pancreas (SPTP). METHODS: The clinical course, surgical treatment, and
      pathological findings of 13 patients with SPTP were analyzed. RESULTS: SPTP has
      no specific clinical symptoms. The patients mostly have abdominal pain and space
      occupying symptoms. Laboratory investigations of some patients showed decreased
      pancreatic exocrine function and elevated CA242 of tumor markers. Ultrasonography
      and CT revealed large solid cystic tumor of pancreas. Digital subtraction
      angiography (DSA) showed lacked-blood-supply space occupying lesion. All tumors
      were resected successfully. The histological findings showed a large encapsulated
      tumor and the section of tumor surrounded by hemorrhagic and necrotic areas. The
      solid areas are composed of small and medium size tumor cells, which had no
      obvious atypia. Psudopapillary structures were found in the cystic degeneration
      areas. Immunohistochemically, most of the tumors were positive for alpha
      antitrypsin (alpha-AT) and vimentin and negative for chromogrannin. No patients
      recurrence during the follow-up. CONCLUSIONS: Most of SPTP can be removed
      successfully after diagnosis. The tumor and local infiltration tissue should be
      removed completely, and the long-term prognosis of SPTP is good.

PMID- 15266838
TI  - [Detection and clinic implication of circulating tumor cell in patients with lung
      cancer].
AB  - Micrometastasis may occur in the early stage of lung cancer and dissemination of
      lung cancer cells into blood circulation is pivotal for metastasis. Many
      approaches, such as polymerase chain reaction, magnetic activated cell sorting,
      flow cytometery, and rare event imaging system, have been developed rapidly. The
      detection of circulating tumor cells may renew the clinical stage and treatment
      of lung cancer.

PMID- 15266839
TI  - [Development of theophylline in treatment of asthma and chronic obstructive
      pulmonary disease].
AB  - Theophylline has been reduced usage in asthma and chronic obstructive pulmonary
      disease because of the high frequency of side effects and the relatively low
      efficacy. However, recent researches have demonstrated that low-dose theophylline
      can not only relax airway smooth muscle but also have anti-inflammatory or
      immunomodulatory actions, which provides theory basis for the treatment of asthma
      and chronic obstructive pulmonary disease.

PMID- 15266840
TI  - [New advance of the molecular targeting agents in advanced non-small cell lung
      cancer].
AB  - Molecule-targeting agents inhibit the proliferation of tumor cells by the
      molecular biological differences between tumor cells and normal cells, and
      finally kill tumor cells. This article introduces several molecule-targeting
      agents that are currently under clinical trials now.

PMID- 15266841
TI  - [Chemotherapy of the elderly patients with advanced non-small cell lung cancer].
AB  - Chemotherapy of the elderly patients with III B/IV stage non-small cell lung
      cancer till remains controversial. We retrospectively reviewed the recent
      literatures, and conclude that single-agent chemotherapy should be the standard
      therapy of the elderly patients with IIIB/IV stage non-small cell lung cancer.

PMID- 15266842
TI  - [Humidification during mechanical ventilation].
AB  - This review aims to emphasize the importance of humidification and to identify
      humidification method the most effective in the intubated or ventilated patients.
      Some details are also discussed on how to perform humidification.

PMID- 15266843
TI  - [Gefitinib for advanced bronchioloalveolar carcinoma].
AB  - We described 3 cases of advanced bronchioloalveolar carcinoma (BAC), in whom once
      daily treatment with 250 mg Gefitinib (Iressa) demonstrated remarkable antitumor
      effects. Gefitinib may produce dramatic clinical responses when administered to
      patients with poor performance status who had received heavy platinum/docetaxel
      based prior chemotherapy.

PMID- 15266844
TI  - [Chemical weapon in the earth].

PMID- 15266845
TI  - [Chemical weapons of the Japanese Imperial Forces and their risk in the
      environment].

PMID- 15266846
TI  - [Poisoning by diphenylarsinic acid derived from chemical warfare agents in
      Kamisu, Japan].

PMID- 15266847
TI  - [Cases of acute gas poisoning due to the chemical weapons excavated at the site
      of the Sagami Arsenal of Imperial Navy].

PMID- 15266848
TI  - [For which cases should clinicians perform blood purification in the management
      of acute poisoning? Clinical and pharmacological analyses].
AB  - Indications for performing blood purification such as direct hemoperfusion (DHP),
      hemodialysis (HD) and hemodiafiltration (HDF) in patients with acute poisoning
      were retrospectively analyzed. Although a quick improvement in consciousness
      level was achieved by an intensive treatment with DHP for three hours in 27
      patients suffering from acute tranquilizer poisoning, a slow but safe recovery
      was surely obtained in another 111 cases who received general supportive care.
      The medical costs of patients treated by DHP were 2.07 times greater than those
      of cases treated by general supportive care. Plasma and urine concentrations of
      theophylline could be obtained simultaneously during the treatment by DHP. The
      excretion rate of DHP at 1, 2, 3 and 6 hours after starting DHP ranged from 99.4%
      to 96.0%. At the end of DHP, the clinical findings markedly improved and
      sufficient elimination from the body could be obtained. The rebound phenomenon
      was observed after three hours DHP in one case of acute anilin poisoning and the
      patient died of fatal fulminant hepatic failure at 9th hospital day. In this
      case, further DHP was needed. DHP is presently becoming less prevalent due to
      concerns over such issues as rapid metabolism and elimination efficacy in acute
      organophosphate and aconitine poisoning. In a case of 23-year old female who took
      a potentially fatal dose of 100 g of acetaminophen, blood purification was not
      performed and oral N acetylcysteine antidotal therapy was quite effective in
      order to prevent hepatic injury. The serum acetaminophen concentration was 287
      microg/ml on her admission and the value fell to 28.8 microg/ml after 35 hours.
      These results indicate that blood purification is not always necessary because of
      it's poor elimination efficacy in some kinds poisoning. Nevertheless, in severe
      cases it was quite an effective and useful extracorporeal elimination technique
      for both improvement of clinical outcome and clearance of poisons. Although it is
      difficult to draw a definitive conclusion from this study, it is suggested that a
      rapid and prudent decision should be made as to perform blood purification.

PMID- 15266849
TI  - [Development of salicylic acid detector tube].
AB  - A detector tube was successfully devised for the screening of salicylic acid in
      urine. It, named "salicylic acid detector tube", consists of glass tube in which
      silica gel coated with 5% (w/w) of ferric chloride is enclosed. A pipette rubber
      cap was attached to an end of the tube, and another end was inserted into urine
      sample. The sample was then introduced into the tube, the color of the reagent
      immediately turned purple under the condition of more than 50 microg/ml of
      salicylic acid in urine. This device was useful for the emergency screening of
      salicylic acid in acute poisoning cases with aspirin.

PMID- 15266850
TI  - [A case of anaphylaxis after a prairie dog bite].
AB  - Several cases of anaphylaxy after hamster bites have recently been reported. We
      report a case of anaphylaxis after a bite from a prairie dog. To our knowledge,
      this is the first case to be reported in Japan. The patient was a 26 year old
      male who was transported to our hospital suffering from dyspnea. The dyspnea
      occurred within several minutes after a bite from a prairie dog to his left
      little finger. He was successfully treated by the administration of epinephrine,
      dopamine and hydrocortisone, and transfusion. Allergies to allergens derived from
      saliva are speculated to be involved in the mechanism of anaphylaxis in cases
      caused by hamster bites. We speculate similar mechanisms may also be involved in
      the case of our patient.

PMID- 15266851
TI  - [Guidelines for the treatment of acute chemical poisoning--7--extracorporeal
      removal of toxins].

PMID- 15266852
TI  - [Practical analysis of toxic substances useful for clinical toxicology--10-
      benzodiazepine].

PMID- 15266853
TI  - [2003 annual report by JPIC].

PMID- 15266854
TI  - What is your diagnosis? Polycystic kidney disease.

PMID- 15266855
TI  - Canine inflammatory bowel disease: retrospective analysis of diagnosis and
      outcome in 80 cases (1995-2002).
AB  - The case records of 80 dogs in which idiopathic inflammatory bowel disease (IBD)
      had been diagnosed were reviewed, and owners were contacted for follow-up
      information using a telephone questionnaire. The types of IBD encountered were
      lymphocytic (n=6), lymphocytic-plasmacytic (n=38), eosinophilic (n=6) and mixed
      inflammation (n=30). Prednisolone, sulphasalazine, metronidazole and tylosin were
      the most frequently prescribed medications. At follow-up, 21 dogs (26 per cent)
      were classified as being in remission (for a median of 14 months), 40 dogs (50
      per cent) had intermittent clinical signs (for a median of 17 months) and three
      dogs (4 per cent) had uncontrolled disease (for a median of 19 months). Ten dogs
      (13 per cent) had been euthanased due to refractory IBD and four of these had
      entered remission for a median of 21 months prior to developing severe relapse
      and refractoriness to further treatment. Six dogs (8 per cent) had been
      euthanased or had died for reasons unrelated to IBD. Hypoalbuminaemia at the time
      of diagnosis was significantly associated with a negative outcome (P=0.0007). No
      association was found between the site (P=0.75), type (P=0.44) and severity
      (P=0.75) of disease. Dietary change to single protein and carbohydrate commercial
      diets had no association with outcome (P=0.12). Owner assessment of quality of
      life at follow-up was significantly associated with outcome (P=0.006).

PMID- 15266856
TI  - Haematological and biochemical abnormalities in canine blood: frequency and
      associations in 1022 samples.
AB  - Submission of blood samples to referral laboratories is very common in veterinary
      practice. Internal reference ranges should take into account published ranges
      adapted to the methods and apparatus used and to the population under
      consideration. The aim of this study was to examine the results from 1022
      consecutive canine blood tests, analysing the frequency and the main associations
      of abnormalities, and to compare the results in different age groups. Haemograms
      and serum biochemistry were compared with internal ranges and between age groups:
      younger than one year, one to eight years and older than eight years. Young dogs
      exhibited lower numbers of erythrocytes and lower values for haemoglobin
      concentration and packed cell volume. They also showed higher numbers of
      lymphocytes and higher concentrations of phosphorus and 71 per cent showed raised
      alkaline phosphatase. Neutrophilia, hypergammaglobulinaemia
      andhypoalbuminaemiaoccurred quite frequently in all dogs, and hypoalbuminaemia
      and hyperphosphataemia were commonly seen in uraemic patients. The simultaneous
      evaluation of cytolytic and hepatobiliary enzymes allowed better detection of
      liver damage, since only a very low percentage of dogs had simultaneous increases
      in all hepatic enzymes.

PMID- 15266857
TI  - Complications of exploratory coeliotomy in 70 cats.
AB  - Records of all cats that had undergone exploratory coeliotomy at the University
      of Edinburgh during the period November 1995 to July 2002 were reviewed. Seventy
      records were retrieved. There were 30 cats in which infection or inflammatory
      disorders predominated, 17 cats with neoplasia, three cats with trauma and 20
      cats with other disorders. Exploratory coeliotomy was performed for diagnostic
      purposes in 28 cats (40 per cent), treatment in 34 cats (49 per cent) and for
      diagnosis and treatment in eight cats (11 per cent). Methods of intraoperative
      diagnosis included incisional biopsy of abdominal organs (52 cats), cytology (two
      cats), microbiology (17 cats) and gross appearance (17 cats). Fifty-eight cats
      (83 per cent) survived the hospitalisation period. Complications occurred in 18
      cats (26 per cent) and were related to anaesthesia (four cats), the underlying
      disease process (15 cats), surgery (five cats) and were undetermined in one cat.

PMID- 15266858
TI  - Successful intravenous human immunoglobulin treatment of drug-induced Stevens
      Johnson syndrome in a dog.
AB  - A two-year-old, male English springer spaniel developed severe mucocutaneous
      ulceration following treatment with trimethoprim-potentiated sulphadiazine. The
      clinical signs were consistent with Stevens-Johnson syndrome (SJS): there were no
      target or arciform lesions typical of erythema multiforme minor and major; more
      than one mucosal surface was affected; epidermal detachment affected less than 10
      per cent of the body surface area; and there was a clear history of drug
      exposure. Systemic signs included a severe hepatopathy, dyspnoea, pyrexia and
      cachexia. Glucocorticoid therapy was associated with secondary infection by
      Pseudomonas aeruginosa. The clinical signs rapidly resolved following a single
      intravenous infusion of 0.51 g/kg human immunoglobulin (ivHIG) as a 5 per cent
      solution. By blocking FAS/FAS ligand (CD95/CD95L) interactions, ivHIG is thought
      to prevent keratinocyte apoptosis. It also binds to immunoglobulin G Fc
      receptors, inhibiting cell activation and cytokine synthesis, neutralises
      autoantibodies and immune complexes, blocks complement activity, is antimicrobial
      and increases colloid osmotic pressure. To the authors' knowledge, this is the
      first report of successful treatment of canine SJS using ivHIG, although it has
      been used to treat erythema multiforme in a cat and toxic epidermal necrolysis in
      a dog.

PMID- 15266859
TI  - Migration of wooden skewer foreign bodies from the gastrointestinal tract in
      eight dogs.
AB  - Wooden skewer foreign bodies were found in eight dogs. Five presented for
      evaluation of draining sinuses and two for inflammatory disease referrable to the
      thorax, abdomen or pelvic region. In an additional case, pneumothorax resulted
      from perforation of the stomach and diaphragm. Ingestion was considered the most
      likely mode of access of the foreign body in all cases. Although the wooden
      foreign bodies were seen radiographically in only two dogs, identification of
      soft tissue or bony changes, or the results of contrast sinography assisted
      diagnosis. Surgical retrieval led to resolution of signs in all cases.

PMID- 15266860
TI  - Phalangeal fractures and metacarpophalangeal luxations subsequent to post
      traumatic osteomyelitis and cellulitis in a dog.
AB  - A working Border collie suffered a puncture wound to the metacarpal pad. No
      fractures or luxations were identified at initial presentation. Treatment was
      instigated with various antibacterials for a period of months. At subsequent
      visits, the dog's condition progressed with development of metacarpophalangeal
      joint luxation and phalangeal fractures secondary to cellulitis and chronic
      osteomyelitis. Amputation was curative. Prompt treatment of the acute condition
      with debridement and drainage may have prevented osteomyelitis becoming
      established in the first instance.

PMID- 15266861
TI  - Intraocular osteosarcoma in a dog.
AB  - A 10-year-old German shepherd dog was presented with unilateral uveitis and
      hyphaema. Treatment was unsuccessful and the eye was enucleated. Intraocular
      osteosarcoma was diagnosed by histological examination.

PMID- 15266862
TI  - Bitten by the travel bug: monitoring exotic diseases in dogs and cats.

PMID- 15266863
TI  - Australian Veterinary Association achieves ban on tail docking.

PMID- 15266864
TI  - Occupational hearing loss: an interdisciplinary challenge.

PMID- 15266865
TI  - Fibroadhesive otitis.

PMID- 15266866
TI  - Recurrent purulent rhinorrhea in an otherwise healthy woman.

PMID- 15266867
TI  - Pyriform sinus hemangioma with calcifications.

PMID- 15266868
TI  - Carotid body tumor (paraganglioma).

PMID- 15266869
TI  - Apical petrositis.

PMID- 15266870
TI  - Vestibular ENG findings in a patient with agoraphobia.

PMID- 15266871
TI  - Removal of a long esophageal foreign body.

PMID- 15266872
TI  - Minimally invasive suture suspension of the brow.

PMID- 15266873
TI  - Seven steps to successfully implementing change.

PMID- 15266874
TI  - Intratympanic steroid perfusion for the treatment of Meniere's disease: a
      retrospective study.
AB  - We conducted a retrospective outcomes review of the charts of 22 patients with
      Meniere's disease who were treated with intratympanic perfusion of
      methylprednisolone and/or dexamethasone. Outcomes were determined by subjective
      assessment of vertigo control and by objective changes in audiometric pure-tone
      average (PTA) and speech discrimination score (SDS). These evaluations were made
      at the first postperfusion visit (short term) and at least 12 months later (long
      term). In the short term, 12 patients (54.5%) achieved vertigo control, 4
      patients (18.2%) demonstrated a greater than 10-dB improvement in PTA, and 1
      patient (4.5%) experienced an increase in SDS of at least 15%. In the long term,
      the corresponding numbers of patients were 4 (18.2%), 2 (9.1%), and 1 (4.5%). The
      level of hearing ultimately deteriorated in 9 patients (40.9%). These findings
      suggest that intratympanic steroid perfusion does not result in any long-term
      alleviation of vertigo or hearing loss. However, the short-term alleviation of
      vertigo seen in approximately half of these patients suggests that this treatment
      may be useful for the temporary relief of symptoms of Meniere's disease.

PMID- 15266875
TI  - Naturally draining ostium of an agger nasi cell: a case report.
AB  - We describe the case of a 61-year-old woman who underwent functional endoscopic
      sinus surgery for chronic hyperplastic rhinosinusitis. During surgery, we were
      able to visualize the natural ostium of her left agger nasi cell. To our
      knowledge, such a finding has not been previously documented in the literature.

PMID- 15266876
TI  - Myofibroma of the cheek: a case report.
AB  - Myofibromas are benign mesenchymal tumors that are commonly found in the dermis
      and subcutaneous tissues of the head and neck. Although most lesions are
      recognized during infancy and early childhood, several cases have been reported
      in older children and adults. We describe the case of a 9-year-old girl who
      presented with a solitary nodule in the left cheek and a history of minor trauma.
      Preoperative imaging detected the presence of a subcutaneous soft-tissue mass
      consistent with a soft-tissue neoplasm rather than a hematoma. Analysis of fine
      needle aspiration material was nondiagnostic. Incisional biopsy revealed that the
      lesion was a myofibroma.

PMID- 15266877
TI  - The roles of the anterior tonsillar pillar and previous tonsillectomy on sleep
      disordered breathing.
AB  - We conducted a study to determine if there is a correlation between inadequate
      anterior tonsillar pillar support and sleep-disordered breathing. We examined 11
      patients with a history of tonsillectomy to ascertain the structural and
      functional integrity of their anterior tonsillar pillars. All 11 demonstrated a
      loss of anterior pillar support and collapse of their soft palate to the extent
      that the soft palate passively pressed against the posterior pharyngeal wall. We
      conclude that a deficiency of anterior tonsillar pillar support does indeed
      predispose patients to obstructive sleep apnea syndrome. Knowledge of this
      correlation can help guide the method of surgical treatment and should reinforce
      the need to maintain the integrity of the anterior tonsillar pillars.

PMID- 15266878
TI  - Comparison of two face masks used to deliver early ventilation to laryngectomized
      patients.
AB  - Emergency airway management of laryngectomized patients is inherently complicated
      by the altered contours of their necks, by the presence of awkwardly placed
      tracheostomas, and by stomal strictures. Effective ventilation can also be
      compromised by the presence of hypertrophic peristomal scar tissue and by tumor
      recurrence. One common method of airway management involves the use of a
      pediatric face mask attached to a standard ventilation bag. We conducted a study
      of 20 laryngectomized patients to determine if they could be adequately
      ventilated through two commonly used pediatric face masks--the Laerdal mask and
      the Ambu mask. Ten of these patients had had an end tracheostoma in place for at
      least 1 year, and the remaining 10 had undergone stoma placement only recently.
      We found that all 20 patients achieved an adequate peristomal seal when using the
      Laerdal mask, whereas only 11 adequate seals were achieved with the Ambu mask.
      Therefore, we recommend that the Laerdal pediatric mask be used for early
      ventilation in laryngectomized patients.

PMID- 15266879
TI  - Percutaneous endoscopic gastrostomy tube feeding in patients with head and neck
      cancer.
AB  - We performed a retrospective chart review of 55 patients who had been treated for
      head and neck cancer to evaluate the complication rate associated with
      percutaneous endoscopic gastrostomy (PEG) for nutritional support. We found that
      complications occurred in only 6 patients (10.9%); 3 of these patients (5.5%) had
      granulation around the site of the PEG tube, and 1 each experienced a tube
      malfunction, migration of the PEG tube, and leakage around the tube. No wound
      infection or other complication associated with PEG tubes was noted. Of the 6
      complications, 3 occurred in 31 patients who underwent PEG tube placement at the
      time of tumor resection, and 3 occurred among 16 patients who received a PEG tube
      postoperatively. We conclude that placement of a PEG tube is a safe method of
      providing nonoral nutritional support for patients with head and neck cancer.

PMID- 15266880
TI  - Crohn's disease of the esophagus.
AB  - Crohn's disease of the esophagus is rare but is being detected more frequently
      because of the use of upper endoscopy. Clinicopathologic correlation is required
      to establish the correct diagnosis. We present a case of esophageal Crohn's
      disease and review the literature to demonstrate that esophageal involvement is
      usually associated with disease elsewhere in the gut.

PMID- 15266881
TI  - Laryngotracheal reconstruction with a muscle-pedicle hyoid bone flap: a series of
      23 patients.
AB  - We conducted a study to evaluate the effectiveness of muscle-pedicle hyoid bone
      flaps in the repair and reconstruction of the larynx and trachea in 23 patients
      who had undergone extended partial laryngectomy. Of this group, 17 patients had
      undergone surgery to correct laryngotracheal stenosis and 6 to remove laryngeal
      carcinoma. Intervention resulted in successful decannulation in 20 of the 23
      patients (87.0%). Of the 3 patients who did not experience a successful outcome
      initially, 2 were successfully decannulated following a second intervention; the
      other patient required a total laryngectomy because of cancer recurrence. In
      light of our follow-up results, we conclude that hyoid bone appears to be an
      effective autograft in such cases.

PMID- 15266882
TI  - Setting up an early warning system for epidemic-prone diseases in the Darfur
      humanitarian crisis.

PMID- 15266883
TI  - Twenty-five years of multidrug therapy for leprosy.

PMID- 15266884
TI  - The effect of raloxifene on cognitive function in postmenopausal women: a
      randomized clinical trial.
AB  - To determine whether treatment with raloxifene has a beneficial effect on
      cognitive function in postmenopausal women, 50 postmenopausal women were
      randomized to receive raloxifene 60 mg, or placebo, for eight weeks. Participants
      completed pre- and post-treatment assessment of cognitive and psychological
      function including the Beck Anxiety and Beck Depression inventories, the SF-36
      Scale of physical and emotional well-being, five tests of cognitive function
      including Block Design and Digit Span subtests of the Wechsler Adult Intelligence
      Scale-III (WAIS-III), the Logical Memory and Paired Associates subtests of the
      Wechsler Memory Scale-III, and the Digit Cancellation test. Results showed no
      significant effect attributable to eight weeks of treatment with raloxifene on
      cognitive, psychological, or health variables.

PMID- 15266885
TI  - Special anesthetic concerns in mentally handicapped institutionalized patients
      undergoing gynecological procedures in an outpatient setting.
AB  - STUDY OBJECTIVE: To evaluate the anesthesia issues involved in caring for
      mentally handicapped outpatients. DESIGN: Retrospective chart review. SETTING:
      University-affiliated outpatient ambulatory center. PATIENTS: Twenty adult
      patients scheduled for gynecological procedures. INTERVENTIONS: None.
      MEASUREMENTS: Data collection sheet was used to record patients' age, ASA status,
      procedure, premedication, intravenous placement, degree of agitation, airway
      control, induction (method and drugs), intraoperative anesthesia care,
      postoperative medications, total time in hospital, postanesthesia care unit time
      and disposition. MAIN RESULTS: Agitation was present in 100% of the patients. A
      significant number of these patients were ASA III, needing oral or intramuscular
      sedation (35%) or mask induction prior to placement of an intravenous line.
      Severely agitated patients had the longest stays in the postanesthesia care unit
      (PACU). CONCLUSIONS: Agitation was the main reason why 90% of the patients
      required intubation for relatively minor procedures. Agitation was the main
      factor leading to prolonged recovery room time.

PMID- 15266886
TI  - Haplotype analysis enables the diagnosis of Marfan syndrome.
AB  - Marfan syndrome is an inherited disorder of connective tissue associated with
      aneurysmal rupture of the ascending aorta. Timely and accurate diagnosis has
      reduced the mortality and morbidity associated with this disorder through
      expectant observation and implementation of appropriate prophylactic therapy. To
      this end, haplotype analysis using polymorphic genetic markers in close proximity
      to the Fibrillin-1 gene (FBN1) were employed to aid in the diagnosis of two
      individuals who did not meet the clinical diagnostic criteria.

PMID- 15266887
TI  - Recurrence of a solitary fibrous tumor of the pleura: a case report.
AB  - We report a case of an 80-year-old female with two prior thoracotomies for benign
      solitary fibrous tumor of the pleura (SFTP) presenting with a two-month history
      of shortness of breath. Computed tomography revealed a pleural-based recurrence
      and operative excision revealed multiple adherent tumors throughout the thoracic
      cavity. Pathologic examination demonstrated malignant degeneration of this
      previously benign tumor. We consider the importance of recurrence of benign SFTP
      and the significance of surgical care and follow up of patients with this rare
      tumor.

PMID- 15266888
TI  - Ruptured thoracic aortic dissection presenting as opacified left hemothorax.
AB  - Acute aortic dissections are uncommon, with a reported incidence of 2000 cases
      per year in the United States. Hemothorax is an unusual but well-described
      complication of ruptured thoracic aortic dissection. It usually occurs on the
      left and can be seen in both proximal and distal dissections. Chest radiographs
      (CXR) in thoracic aortic dissections often reveal a widened mediastinum or
      abnormal aortic silhouette, evident in 80%-90% of cases. However, CXR may be
      normal in about 12% of patients with aortic dissection. Clues that would indicate
      aortic dissection such as abnormal aortic silhouette and widened mediastinum may
      be obscured by an opacified hemothorax caused by rupture of a thoracic aortic
      dissection. A high index of suspicion is necessary to make a diagnosis of
      ruptured thoracic aortic dissection in a patient presenting with hemothorax. This
      is illustrated in the case described.

PMID- 15266889
TI  - Why health insurers care about the medical malpractice crisis current status?:
      Code blue.

PMID- 15266890
TI  - Professional liability insurance reform: epilogue.

PMID- 15266891
TI  - For profit or for better medical care?

PMID- 15266892
TI  - On chiropractic.

PMID- 15266893
TI  - Inhibitors of measles virus.
AB  - Measles virus (MV) infections have been almost eradicated in some industrialized
      nations. However, MV continues to cause severe disease and mortality in the world
      and is responsible for clusters of exogenous-borne disease in essentially disease
      free countries. Because of the ebb and flow of immunization campaigns, especially
      in the poverty-stricken and war-torn Third World, and the ominous potential for
      severe disease and mortality, it is vital that research for discovery of
      therapeutic countermeasures should continue. To that end, a number of compounds
      have been evaluated for efficacy in vitro and in animal models, and several
      therapeutic modalities have been tested in the clinic. The only current therapies
      used in the clinic include ribavirin administered orally or intravenously, alone
      or in combination with immune serum globulin; these therapies have demonstrated
      variable efficacy. Therefore, drug discovery efforts have been launched to
      supplement the existing treatments for MV infections. Antisense molecules,
      adenosine and guanosine nucleosides, including ring-expanded 'fat' nucleoside
      analogues, brassinosteroids, coumarins, peptide inhibitors, modulators of
      cholesterol synthesis and a variety of natural products have been screened for
      efficacy and toxicity both in vitro and in animals. However, none of these agents
      has gone into human clinical trials and most will not merit further development
      due to toxicity concerns and/or low potency. Thus, further research is needed to
      develop more potent and less toxic drugs that could be used for treating MV
      infections to supplement the existing MV vaccine campaigns.

PMID- 15266894
TI  - Clinical utility of current NNRTIs and perspectives of new agents in this class
      under development.
AB  - Highly active antiretroviral therapy (HAART) has significantly reduced the number
      of deaths caused by AIDS. However, the antiviral efficacy of HAART comprising
      protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs)
      is frequently accompanied by a decrease in patients' quality of life. PI-based
      therapies often fail due to poor adherence caused by heavy pill burden, complex
      dosing schedules and undesirable side effects. The current trend is to switch
      from PI-based to PI-sparing regimens consisting of non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) and NRTIs. Despite some encouraging results
      from NNRTI-containing therapies, two major concerns in using the currently
      available NNRTIs remain: 1) low genetic barrier to the emergence of resistance
      and 2) cross-resistance due to single mutations that often render the whole class
      of NNRTIs ineffective. Clearly, new and improved NNRTIs are needed to address
      these concerns.

PMID- 15266895
TI  - Helicase primase: targeting the Achilles heel of herpes simplex viruses.
AB  - The majority of the population is infected by several herpesviruses. Once these
      infections are established the viruses persist for life. Therefore, current
      therapy may at best reduce symptoms but does not cure the infection. Moreover,
      the only classes of compounds licensed for systemic treatment of disease are
      nucleoside, nucleotide and pyrophosphate analogues; all of these ultimately
      target the herpesvirus DNA polymerase. A vaccine against varicella zoster virus
      (VZV) is available, but so far no effective vaccines against other human
      herpesviruses have been launched. At the same time, rising resistance to current
      medication, especially in the immunocompromised patient population, is a concern.
      For these reasons, there is an urgent need for new treatment options. Recently,
      some promising new drugs have been discovered; one of these compounds, developed
      at Bayer HealthCare under the name BAY 57-1293, is a potent HSV helicase primase
      inhibitor.

PMID- 15266896
TI  - Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV:
      implications for the treatment of hepatitis C.
AB  - Alpha-glucosidase I inhibitors have been shown to inhibit the replication of a
      broad range of enveloped viruses by preventing the correct folding of their
      envelope glycoproteins. This study assesses the potential of 6 O-butanoyl
      castanospermine (celgosivir) as a treatment for hepatitis C virus (HCV). In the
      absence of an adequate culture system for HCV, the closely related virus, bovine
      viral diarrhoea virus (BVDV), was used as a surrogate model. Using both a plaque
      assay and a cytopathic effect assay, celgosivir (IC50 16 and 47 microM
      respectively) was shown to be more potent than N-nonyl DNJ (105 and 74 microM),
      castanospermine (110 and 367 microM) and N-butyl DNJ (> 250 and 550 microM). Of
      the alpha-glucosidase inhibitors tested, only N-nonyl DNJ showed evidence of
      toxicity (CC50 > or = 120 microM). Two-way combinations of interferon-alpha,
      ribavirin and either celgosivir or castanospermine demonstrated that each could
      enhance the antiviral efficacy of the others, either additively or
      synergistically. The observation that the number of viral genomes released from
      BVDV-infected cells was inhibited by either castanospermine or celgosivir in
      parallel with the number of infectious units was taken as confirmation that these
      alpha-glucosidase I inhibitors block the production or release of flavivirus
      particles.

PMID- 15266897
TI  - Inhibitory effect of medicinal herbs against RNA and DNA viruses.
AB  - Fifteen Argentine medicinal plants were tested for their antiviral activity in
      vitro against herpes simplex viruses types 1 and 2 (HSV-1 and 2), bovine viral
      diarrhoea virus type 1 (BVDV-1), influenza virus type A (Inf A) and human
      immunodeficiency virus type 1 (HIV-1). Antiviral activity was evaluated by a
      reduction in cytopathic effect, plaque-forming units and p24 HIV-1 antigen. The
      Selective Index of the active extract (SI(extract) = CC50(extract)/EC50(extract))
      of Coronopus didymus (SI(extract) = 110.7), Juglans australis (SI(extract) = 8.1)
      and Lippia alba (SI(extract) = 19.2) against BVDV-1, HSV-1 and influenza A virus,
      respectively, justify a further analysis. None of the seven plants assayed
      against HIV-1 displayed any antiviral activity. The results of this study justify
      the continuing isolation and characterization of the antiviral components
      present.

PMID- 15266898
TI  - Attempt to reduce cytotoxicity by synthesizing the L-enantiomer of 4'-C-ethynyl
      2'-deoxypurine nucleosides as antiviral agents against HIV and HBV.
AB  - We investigated the potential of 4'-C-substituted nucleosides for the treatment
      of HIV-1 and HBV. Of the nucleosides we prepared, several 4'-C-ethynyl-2'
      deoxypurine nucleosides showed the most potent anti-HIV activity. However, two
      candidates, 4'-C-ethynyl-2'-deoxyguanosine and 9-(2-deoxy-4-C-ethynyl-beta-D-ribo
      pentofuranosyl)-2,6-diaminopurine, were very toxic during in vivo study. On the
      other hand, lamivudine (3TC) is known to show remarkable activity against HIV and
      HBV with lower cytotoxicity. Therefore, we attempted to synthesize the L
      enantiomer of 4'-C-ethynyl-2'-deoxypurine nucleosides in 20-21 steps. These
      methods consisted of preparing 4-C-ethynyl-L-sugar, starting from D-arabinose and
      then condensing the L-sugar derivative with 2,6-diaminopurine. 4'-C-Ethynyl-2'
      deoxyguanosine was also prepared by enzymatic deamination from the 2,6
      diaminopurine derivative. The compounds' antiviral activity against HIV and HBV
      was then evaluated. Unfortunately, they demonstrated no activity and no
      cytotoxicity.

PMID- 15266899
TI  - Hepatitis C virus (HCV)--a review molecular biology of the virus,
      immunodiagnostics, genomic heterogeneity and the role of virus in hepatocellular
      carcinoma.
AB  - Hepatitis C virus (HCV), an RNA and a hepatotropic virus, is the leading cause of
      viral hepatitis worldwide. Infection with this virus causes a repertoire of liver
      diseases that include acute hepatitis, chronic hepatitis, cirrhosis and
      hepatocellular carcinoma (HCC), in addition to a number of extra-hepatic
      manifestations such as lichen planus, oral cancer, etc. At present, patients
      infected with this virus are treated with interferon either alone or in
      combination with ribavirin, a guanosine-like nucleoside analog. However, response
      to this treatment has been rather disappointing. For about a decade, lack of an
      alternative animal model other than chimpanzee, and an efficient cell culture
      system that could support long-term replication of the virus, hampered research
      on HCV. Despite this, a significant amount of information with regard to the
      molecular biology of the virus is available using bacterial cloning-expression
      systems, and based on computer predictions and analysis. Recent discovery of a
      cellular receptor to which the virus binds, identification of efficient cell
      culture/cell-free systems, HCV replicons and the development of a chimeric mouse
      model, provide a platform to verify the existing knowledge about this virus in
      the coming years. Additionally these developments aid the researchers in
      identifying novel therapeutic agents, apart from allowing us to reassess the
      efficiency of the currently available therapeutics. Presented in this article are
      a review of existing information with regard to the molecular biology of the
      virus, immunodiagnostic assays, genomic heterogeneity and the role of the virus
      in hepatocellular carcinoma. Likely therapeutic strategies other than those
      currently available are also introduced.

PMID- 15266900
TI  - Tissue engineering: in vitro embryonal nidation in a murine endometrial
      construct.
AB  - The epithelial and mesothelial cellular components of organs can be obtained as
      dissociated cells using adequate procedures of enzymatic digestion followed by
      pycnotic separation on density gradients. Using a specially developed procedure
      for tissue dissociation, the epithelial and connective tissue components of
      endometria from pseudopregnant mice were grown in culture using a combination of
      three dimensional culture of connective tissue components in collagen gel, with
      the superimposition of epithelial components in liquid medium on the surface of
      the gells. After a few days of growth, when the cultures became dense, murine
      blastocysts obtained on postcoital day 4.5 by fallopian flushing of hormonally
      primed and mated mice, were transferred onto the imitated endometria. The
      blastocysts hatched and grew on the endometrial epithelium as spherical coherent
      conglomerates of cells quite different from hatched blastocysts grown on the
      surface of a petri dish, in which the presumtive trophoblasts spred around the
      central mass. Light and electronmicroscopy of resin embeded sections (2 days
      after nidation on the simulated endometria) revealed that at least two
      populations of cell types were recognisable as layers. This is interpreted as an
      early sign of morphogenesis and the first visible steps of differentiation. The
      presence of mitotic figures indicates viability and continuing growth.
      Electronmicroscopy of cell types grown under conditions simulating in vivo tissue
      architectonics showed overtly less cytopathology and better cell function.
      Simulated endometria may, therefore, serve as an attractive model for studying
      early mammalian embryogenesis and the effects of toxic agents.

PMID- 15266901
TI  - Site specific integration of FLP recombinase in BHK-21 cell line.
AB  - A binary system for gene activation and site specific integration based on
      conditional recombination of transfected sequences mediated by FLP recombinase
      from yeast was implemented in mammalian cells. In several cell lines, FLP rapidly
      and precisely recombined copies of its specific target sequences to activate an
      otherwise silent beta-galactosidase reporter gene. Clones of marked cells were
      generated by excisional recombination within a chromosomally integrated copy of
      the silent reporters. These clones exhibited intense blue colour with X-Gal
      staining solution.

PMID- 15266902
TI  - Vasopressin mediates neuroprotection in mice by stimulation of V1 vasopressin
      receptors: influence of PI-3 kinase and gap junction inhibitors.
AB  - Neuroprotective effect of vasopressin analogues, arginine Vasopressin (AVP) and
      lysine Vasopressin (LVP) was evaluated against MgCl2 induced cerebral ischemia
      model. AVP significantly prevented (P < 0.01) MgCl2 (1M) induced cerebral
      ischemia as compared to lysine Vasopressin (LVP) which was less effective (P <
      0.05). Pretreatment with PI-3 kinase inhibitors, Wortmannin and LY-294002 (50
      microg/kg, ip) significantly attenuated the protective effects of vasopressin.
      AVP was also effective in reducing the maximal electroshock (MES) induced
      convulsive time and this protective effect was blocked by PI-3 kinase inhibitors.
      On the other hand, pretreatment with gap junction intracellular communication
      (GJIC) blocker, mephenamic acid (30 mg/kg, ip) significantly potentiated the
      MgCl2 induced cerebral ischemia. This enhancement of cerebral ischemia was not
      reversed by vasopressin analogue, LVP. The role of V1 vasopressin receptor was
      evaluated by pretreating the animals with non-selective V1 receptor antagonist,
      des Gly-NH2, d (CH2)5 [D-Tyr2, Thr4] OVT which reversed the effects of AVP
      suggesting a role for vasopressin V1 receptors. This study suggests that
      neurohypophyseal hormone, AVP is neuroprotective against MgCl2 induced cerebral
      ischemia and this effect is modulated by PI-3 kinase enzyme inhibitors and
      protein kinase C inhibitors through possible influence on the cerebral vascular
      tone. This study suggests that gap junctions have potential role in the induction
      of MgCl2 induced cerebral ischemia.

PMID- 15266903
TI  - Effects of low level pulsed radio frequency fields on induced osteoporosis in rat
      bone.
AB  - Effect of modulated pulsed electromagnetic fields (PEMFs; carrier frequency, 14
      MHz. modulated at 16 Hz of amplitude 10 V peak to peak) on sciatic neurectomy
      induced osteoporosis in rat femur and tibia resulted in statistically significant
      increase in bone mineral density, and deceleration in bone resorption process and
      consequently further osteoporosis in rat bone. These results suggest that such an
      effective window of pulsed radio frequency fields may be used therapeutically for
      the treatment of osteoporosis.

PMID- 15266904
TI  - Influence of aluminium on neurotoxicity of lead in adult male albino rats.
AB  - Influence of aluminium on neurotoxicity of lead was studied in male albino rats.
      Aluminium enhanced the net deposition of lead in brain. This was further
      substantiated by higher levels of malondialdehyde (MDA), and lower activities of
      acetylcholinesterase enzyme in the brain homogenates of the rats treated with
      both lead and aluminium as compared to those of rats treated with lead only. In
      lead plus aluminium treated animals, a significant neurological deficit was
      observed when the animals were subjected to rota-rod, traction performance (TP)
      and tail immersion tests.

PMID- 15266905
TI  - Immunotoxicological effects of dermal application of scum of waste crankcase oil
      in mice.
AB  - The scum of waste crankcase oil (SWCO) forms due to weathering of waste crankcase
      oil, deposited on the surface of water bodies. It is known to attach to the
      feathers of aquatic birds and cause toxicity to the eggs of nestling birds. The
      water bodies contaminated with SWCO can also be a source of toxicity to the human
      beings and animals entering such bodies. Since SWCO used in the present study had
      an appreciable content of heavy metals like Zn, Pb, Cd, Mn, Cr and Ni, the
      present investigation was undertaken to study a probable effect on immune system
      of mice. Animals treated with SWCO at a dose of 0.5, 1.0, 2.0, or 4.0 g/kg body
      weight for 28 days, had no effect on the weight gain of vital organs. A
      depressing effect was observed on the cell population of spleen and thymus. The
      number of primary antibody (IgM) producing cells was significantly depressed in
      spleen. The IgM antibody titer of serum, reduction of NBT dye by peritoneal
      exudat cells and mounting of delayed hypersensitivity response were not affected.
      In view of above immunotoxic effects of SWCO, the waste crankcase oil should be
      carefully disposed of, away from water bodies.

PMID- 15266906
TI  - Comparative role of proteins in transport of HCH-isomers in desert locust,
      Schistocerca gregaria Forskal and bovines.
AB  - The studies on binding of hexachlorocyclohexane (HCH) with carrier proteins were
      carried out to establish the role of proteins in the transport of insecticides in
      insects. Sephadex G-200 column chromatography resolved haemolymph of adult male
      desert locust, Schistocerca gregaria into three major protein peaks. There was
      significant binding of gamma-HCH with first protein peak (F1). Two classes of
      binding sites were observed on first protein peak for gamma-HCH. However low
      level of binding was observed with the third protein peak (F3) of the haemolymph.
      Bindings of HCH-isomers (alpha, beta and gamma) with bovine serum albumin (BSA)
      were not related to their water solubilities. Moderate to low affinities (1.4 
      1.84 x 10(6) M(-1)) of HCH-isomers for BSA were observed. The present studies
      showed that more HCH binds to haemolymph lipoprotein of locust as compared to
      BSA. This indicates a significant role of haemolymph proteins in the transport of
      insecticides in insects.

PMID- 15266907
TI  - Karyotype, Ag-NOR, CMA3 and SEM studies in a fish (Mystus tengara, Bagridae) with
      indication of female heterogamety.
AB  - Somatic karyotypes in M. tengara contained 54 chromosomes, comprising 26
      homomorphic pairs in both sexes and one pair of heteromorphic nature in female
      (one big submetacentric and one small subtelocentric chromosomes), while in males
      this pair was homomorphic (with two big sub-metacentric chromosomes). The
      Nucleolus Organizer Regions (NORs) were located at one arm of the suspected sex
      elements in both sexes, while another pair of metacentric chromosomes (No.7) also
      showed Ag-positive arm. The CMA3 technique revealed relatively bright fluorescing
      zones in the regions of chromosomes that showed Ag-positive staining, revealing
      thereby the preponderance of GC-rich active sites of rRNA genes in NORs. SEM
      studies revealed clear heteromorphism to exist in the elements suspected as sex
      chromosomes in females.

PMID- 15266908
TI  - Detection and characterization of enterocins from Enterococcus sp.
AB  - Examination of 90 isolates of Enterococcus sp. revealed production of enterocin
      by two isolates of E. faecalis which was inhibitory to Listeria monocytogenes.
      Two isolates of E. gallinarum produced enterocin active against Staphylococcus
      aureus. None of the isolates antagonized Salmonella enteritidis. The enterocins
      of E. faecalis isolates were inactivated by alpha-chymotrypsin but not by trypsin
      and papain, while those of E. gallinarum were resistant to all the three enzymes.
      Enterocins produced by all 4 strains were resistant to heating at 60 degrees C
      for 30 min and 80 degrees C for 10 min, but sensitive to 121 degrees C for 15
      min. At 100 degrees C for 10 min, two enterocins, one each of E. faecalis and E.
      gallinarum were inactivated, while the remaining two retained the bactericidal
      activity.

PMID- 15266909
TI  - Isolation and purification of an extracellular protease from a new strain of
      Bacillus subtilis, viz.NCIM 2711.
AB  - A new extracellular protease having a prospective application in the food
      industry was isolated from Bacillus sUbtilis NCIM 2711 by (NH4)2SO4 precipitation
      from the cell broth. It was purified using DEAE-Cellulose and CM-Sephadex C-50
      ion-exchange chromatography. With casein as a substrate, the proteolytic activity
      of the purified protease was found to be optimal at pH 7.0 and temperature 55
      degrees C with Km 1.06 mg/ml. The enzyme was stable over a pH range 6.5-8.0 at 30
      degrees C for 1 hr in presence of CaCl2 x 2H2O. At 55 degrees C, the enzyme
      retained 60% activity up to 15 min in presence of CaCl2 x 2H2O. EDTA and o
      phenanthroline (OP) completely inhibited the enzyme activity while DFP, PMSF and
      iodoacetamide were ineffective. The enzyme was completely inhibited by Hg2+ and
      partially by Cd2+, Cu2+, Ni2+, Pb2+ and Fe2+. The OP inhibited enzyme could be
      reactivated by Zn2+ and Co2+ up to 75% and 69% respectively. It is a neutral
      metalloprotease showing a single band of 43 kDa on SDS-PAGE.

PMID- 15266910
TI  - Xylanase production by Ganoderma lucidum on liquid and solid state fermentation.
AB  - Ganoderma lucidum, a white rot fungus, was exploited for its potentials to
      produce xylanase employing shake and solid-state culture conditions. Different
      culture conditions such as pH, temperature, carbon and nitrogen requirements for
      its growth and production of xylanase were optimized. The culture media pH 6.0
      7.0 and temperatures 30 degrees-35 degrees C significantly promoted the growth as
      well as xylanase secretion into the media. Xylan and peptone were found to be the
      suitable carbon and nitrogen sources. Among the different agrowastes used, wheat
      bran was found to be the best substrate for the test fungus for the production of
      xylanase than sugarcane bagasse and rice bran in solid-state fermentation.

PMID- 15266911
TI  - Rhizoctonia wilt suppression of brinjal (Solanum melongena L) and plant growth
      activity by Bacillus BS2.
AB  - An antibiotic-producing and hydrogen-cyanide-producing rhizobacteria strain
      Bacillus BS2 showed a wide range of antifungal activity against many Fusarium sp.
      and brinjal wilt disease pathogen Rhizoctonia solani. Seed bacterization with the
      strain BS2 promoted seed germination and plant growth in leguminous plants
      Phaseolus vulgaris and non-leguminous plants Solanum melongena L, Brassica
      oleracea var. capitata, B. oleraceae var. gongylodes and Lycopersicon esculentum
      Mill in terms of relative growth rate, shoot height, root length, total biomass
      production and total chlorophyll content of leaves. Yield of bacterized plants
      were increased by 10 to 49% compared to uninoculated control plants. Brinjal
      sapling raised through seed bacterization by the strain BS2 showed a
      significantly reduced wilt syndrome of brinjal caused by Rhizoctonia solani.
      Control of wilt disease by the bacterium was clue to the production of antibiotic
      like substances, whereas plant growth-promotion was due to the activity of
      hydrogen cyanide. Root colonization study confirmed that the introduced bacteria
      colonized the roots and occupied 23-25% of total aerobic bacteria, which was
      confirmed using dual antibiotic (nalidixic acid and streptomycin sulphate)
      resistant mutant strain. The results obtained through this investigation
      suggested the potentiality of the strain BS2 to be used as a plant growth
      promoter and suppressor of wilt pathogen.

PMID- 15266912
TI  - Fatty acids derived from a marine crustacean Diogenes avarus (Heller) and their
      antiangiogenic activity.
AB  - An organic extract from a marine crustacean D. avarus was examined for
      antiangiogenic activity by using the chick embryo chorioallantoic membrane (CAM)
      assay. The methanol extract (HCM) inhibited angiogenesis in a dose dependent
      manner. The extract was further fractionated by bioactivity-guided separation to
      purify the active fractions successively. This resulted in three fractions HCM1,
      HCM2 and HCM3. The 50% inhibition shown by HCM was 600 ng/disc, HCM1 was 100
      ng/disc and of HCM3 was 2.7ng/disc. HCM3 which was separated by column
      chromatography and showed single spot on TLC was analysed by GLC and showed the
      presence of saturated and unsaturated fatty acids such as lauric, myristic,
      palmitic, stearic, oleic, linoleic. The antiangiogenic activity of the fatty
      acids obtained from a marine crustacean is reported for the first time.

PMID- 15266913
TI  - Lowering of blood sugar by water extract of Azadirachta indica and Abroma augusta
      in diabetes rats.
AB  - Combination (1:1 ) of water extract of dried powder of root and leaves (200 mg/kg
      body wt) of A. augusta and A. indica respectively was administered orally to
      alloxan diabetic rats once a day for 8 weeks. This treatment caused significant
      lowering of blood sugar in fasted as estimated by glucose tolerance test. The
      treatment resulted in a significant reduction in serum lipids. Aqueous extract
      also decreased the formation of lipid peroxides estimated as thiobarbituric acid
      reactive substance, (TBARS), and increased antioxidants (superoxide dismutase,
      catalase, glutathione peroxidase and glutathione transferase) in erythrocytes.
      There was reduction in LPO as TBARS in heart, liver, kidney, and muscles. It also
      prevented decrease in body weight. Present study showed that Abroma augusta roots
      and A. indica leaves when given together as water extract had hypoglycaemic
      action and had better effect than given alone.

PMID- 15266914
TI  - Anti-steroidogenic activity of methanolic extract of Cuscuta reflexa roxb. stem
      and Corchorus olitorius Linn. seed in mouse ovary.
AB  - Methanolic extract (ME) of both C. reflexa stem and C. olitorius seed arrested
      the normal oestrus cycle of adult female mouse and significantly decreased the
      weight of ovaries and uterus. The cholesterol and ascorbic acid contents in
      ovaries were significantly increased in the treated mice. Two key enzymes, delta5
      3beta-hydroxysteroid dehydrogenase and glucose-6-phosphate dehydrogenase, were
      decreased significantly in ME of both C. reflexa stem and C. olitorius seed after
      17 days of treatment. High level of substrates and low level of enzymes indicate
      the inhibition of steroidogenesis in treated mice and may be due to the presence
      of flavonoids.

PMID- 15266915
TI  - Pyramid environment reduces the wound healing suppressant properties of
      dexamethasone in albino rats.
AB  - With a view to investigate the contribution and role of environment within a
      wooden pyramid model on the wound healing suppressant effect of dexamethasone in
      rats, wound breaking strength, dry weight, hydroxyproline content and histology
      of granulation tissue of the dead space wound were studied in rats. The results
      indicate that the environment within the wooden pyramid not only promotes
      significant wound healing but also reduces the wound healing suppressant effect
      of dexamethasone. Histological studies also confirmed the results.

PMID- 15266916
TI  - Analgesic activity of Piper longum Linn. root.
AB  - Piper longum root, commonly called Kandantippili, is traditionally used to treat
      rheumatism, insomnia, palsy and epilepsy. But a scientific study on its central
      actions is not available. This study screens P. longum root for opioid type
      analgesia using rat tail-flick method and for NSAID type analgesia using acetic
      acid writhing method. Pentazocine (ip) and ibuprofen (oral) are used as
      respective drug controls. An aqueous suspension of P. longum root powder is given
      orally to mice and rat in doses of 200, 400 and 800 mg/kg. The delay in reaction
      time for thermal stimulus in rats and the number of writhings to chemical
      stimulus in mice are determined in each group. The results are analysed
      statistically. The 400 and 800 mg/kg doses of P. longum show significant NSAID
      type of analgesia (P < 0.001). Both Ibuprofen (40 mg/kg) and P. longum (800
      mg/kg) show 50% protection against writhing. The delay in reaction time to
      thermal stimulus was less than 6% for different doses of P. longum as against
      100% for pentazocine. This indicates that P. longum root has weak opioid but
      potent NSAID type of analgesic activity.

PMID- 15266917
TI  - Trace element concentration in various tissues following fluoride administration
      to female mice.
AB  - Brain, liver, kidney and muscles demonstrate significant changes in essential
      trace element (Cu, Zn, Mn and Fe) level in adult female mice given 30, 60 and 120
      ppm sodium fluoride (NaF) in drinking water. These changes involve excess removal
      or accumulation of these trace elements in respective tissues. Changes observed
      were dose dependent and significant at 120 ppm NaF concentration in drinking
      water.

PMID- 15266918
TI  - Field evaluation of difethialone, a new second generation anticoagulant
      rodenticide in the rice fields.
AB  - A new second generation anticoagulant rodenticide, difethialone (0.0025%), was
      evaluated in the rice fields at three different cropping stages, viz. Milky,
      Panicle formation and Panicle maturation, during Kuruvai and Thaladi seasons. The
      difethailone (0.0025%) yielded satisfactory control success suggesting a great
      potential as a rodenticide especially in the early stages of rice.

PMID- 15266919
TI  - Evaluation of coronary artery disease.

PMID- 15266920
TI  - Adenosine myocardial SPECT--its efficacy and safety and correlation with coronary
      angiogram.
AB  - OBJECTIVE: The aim of this study was to determine the safety and efficacy of
      adenosine Tc99m sestamibi myocardial perfusion study under controlled conditions
      and to correlate the adenosine Tc99m sestamibi perfusion defects and the coronary
      angiography in patients investigated for coronary artery disease. METHODS: This
      prospective study included 122 consecutive patients who underwent adenosine Tc99m
      sestamibi single photon emission computed tomography (SPECT) myocardial perfusion
      study. Seventy two patients had coronary angiographic correlation. All the
      patients who were referred by the cardiologists for stress myocardial perfusion
      scan who could not be stressed physiologically for one reason or the other were
      included in the study. RESULTS: Among the coronary angiography group the overall
      sensitivity, specificity, positive predictive value and negative predictive value
      of adenosine Tc99m sestamibi single photon emission computed tomography
      myocardial perfusion study for detecting significant coronary obstruction
      (diameter > or = 50%) were 94.4%, 79%, 85% and 92% respectively. The side effects
      were transient and required no treatment. CONCLUSION: We conclude adenosine Tc99m
      sestamibi single photon emission computed tomogram myocardial perfusion study is
      a reliable test with high sensitivity and specificity for the detection of
      coronary artery disease.

PMID- 15266921
TI  - Treadmill ECG test combined with myocardial perfusion imaging for evaluation of
      coronary artery disease: analysis of 340 cases.
AB  - AIM: Using Coronary arteriogram as the gold standard, stress ECG (Treadmill Test 
      TMT) has a sensitivity of 68% and specificity (77%) for the detection of
      coronary artery disease (CAD). Stress myocardial perfusion imaging (MPI) with Tc
      99m Sestamibi gated SPECT has a sensitivity of 85% and specificity of 90%. The
      aim of the study was to ascertain if the combined use of the two physiologic
      tests will raise the predictive value for the presence or absence of
      physiologically significant CAD to 100%. METHODS AND MATERIAL: Three hundred and
      fourty patients (200 with suspected and 140 proved CAD) were studied with the
      same day rest and stress protocol. A rest MPI image was acquired with 8 mCi Tc
      99m Sestamibi, followed by TMT; at the peak exercise 20 mCi tracer was injected
      and post-stress MPI image was acquired after 1 hour. 12-lead ECG at rest and
      during stress and recovery period was analyzed. RESULTS: Out of 200 patients with
      a prior probability of CAD 40-50% (151 with pain in chest, 81 with shortness of
      breath on exertion and 68 asymptomatic high risk for CAD--more than 5/9 risk
      factors), a normal stress MPI result in 150 patients excluded the probability of
      physiologically significant CAD. Fifty patients with abnormal stress MPI were
      refered for coronary arteriography. Stress ECG had 17% "false negative" and 23%
      "false positive" compared to stress MPI. In this group out of 140 known CAD, (56
      post-infarct, 52 post-CABG and 32 post-PTCA), all sent for evaluation of ischemic
      symptoms, MPI documented 101 infarcts (fixed defects with no wall motion and
      thickening), 20 of them were "silent" (with no history of previous infarct) ECG
      did not help in picking them up. 58/101 infarcts had only fixed defects while
      43/101 were accompanied by reversible ischaemia in same or other vascular
      territories. Thirty nine patients showed only reversible ischaemia without any
      infarct. Risk stratification was possible based on the extent and severity of the
      perfusion defects and number of territories in which defects were seen, rest
      LVEF, size of LV and transient dilation CONCLUSIONS: Combined stress ECG and
      stress MPI perform "gate keeper" function for referral for angiography, as well
      as for risk stratification of those who already have coronary angiograms.
      Decisions for revascularization should be based on combined evaluation--a shift
      from stenosis- based to ischaemic--based evaluation. Success or failure of
      revascularization was also documented by this evaluation.

PMID- 15266922
TI  - Hypertension in the elderly population of Assam.
AB  - BACKGROUND: With the increase in life-expectancy and modification of lifestyle
      cardiovascular disease especially hypertension is emerging as a major public
      health problem in the elderly people of Assam. The Geriatric population needs
      priority in assessment of the disease burden. With this background this study was
      undertaken with an objective to know the dimension of the hypertension prolem in
      elderly people of Assam and relevant factors associated with it. METHODS: Eight
      hundred and eighty eight elderly participants 60 years and above (males 500,
      females 388 from three randomly selected areas were interviewed to collect
      information on dietary habit and socio-demographic variables and clinically
      examined for blood pressure and athropometric parameters using standardized
      technique. Statistical analysis was performed using the Epi Info and SPSS
      software. RESULTS: To overall age adjusted mean systolic blood pressure (SBP) was
      150.52 (95% CI 148.81-152.23) and diastolic blood pressure (DBP) was 88.22 (95%
      CI 87.39-89.05). Overall prevalence of hypertension was 63.63% (95% CI 59.8
      66.2), 64.2% in males and 62.89% in females. Isolated systolic hypertension was
      detected in 13.2% males and 10.31% females among the hypertensives. 26.90% of the
      hypertensives were aware of their increase in blood pressure. Determinants of
      hypertension derived by multiple logistic regression analysis were age, intake of
      extra salt, alcohol and body mass index (BMI). CONCLUSION: High prevalence with
      inadequate awareness and control of hypertension in the elderly group of
      population call for an immediate implementation of active public health programme
      in the state.

PMID- 15266923
TI  - Cutaneous vasculitis--a dynamic process posing diagnostic challenge.
AB  - AIM: To characterize the clinicopathologic features and to assess the therapeutic
      outcome in cutaneous vasculitis. MATERIAL AND METHODS: Fifty biopsy proven cases
      of cutaneous vasculitis seen between January 1998 and July 1999 were studied.
      RESULTS: The commonest presentation was palpable purpura. The site most commonly
      affected was the extremity, irrespective of the age (adults - 40 and children -
      10) and sex. The histopathologic picture ranged from an acute to chronic process,
      which besides the classic picture included bullous presentation, granulomatous
      histology and nonspecific features. Clinical correlation and investigations
      including direct immunofluorescence (DIF) were required to differentiate primary
      from secondary vasculitis (SLE-4, dermatomyositis-2, rheumatoid artritis-1, HIV
      1, septicaemia-1 and drug reaction 2). DIF was diagnostic in 13 out of 21 cases
      providing evidence of an immune-mediated pathogenesis. Drugs used in the
      treatment included dapsone, colchicine, pentoxyphiline and steroids. CONCLUSIONS:
      The clinical picture and outcome of primary cutaneous vasculitis were benign
      while the prognosis of secondary vasculitis depended on the primary disease,
      irrespective of the histopathological picture.

PMID- 15266926
TI  - Thromboangiitis obliterans in a young male.

PMID- 15266925
TI  - Clinical profile in gelatinous bone marrow transformation.
AB  - OBJECTIVE: To study the clinical spectrum associated with gelatinous bone marrow
      transformation (GMT). METHODS: All subjects whose bone marrow aspiration showed
      pink purple material on Leishman stain underwent a detail history, clinical
      examination and investigation (biochemical/microbiological/radiological).
      Additionally, in each subject the smear was stained with special stains of
      Periodic Acid Schiff and Alcian blue. RESULTS: Out of total 1498 marrows, 65
      showed evidence of GMT. All of these had anaemia. The associated clinical spectra
      of diseases noticed were: Infection (31 cases), Nutritional deficiency (5 cases),
      Haematological disorders (Aplastic/toxic depression) (17 cases), Malignancies (3
      cases), and Miscellaneous (9 cases). CONCLUSION: Based on the heterogenecity of
      associated clinical disorders, GMT indicates severe illness and not a particular
      disease. GMT may be a result of bioregulatory process (which presently needs
      further prospective studies) that are activated in different pathologic
      conditions but resulting in similar lesion in the bone marrow and so till then it
      may be concluded that GMT is a symptom of bone marrow.

PMID- 15266924
TI  - Celiac disease in osteoporotic Indians.
AB  - OBJECTIVE: 1) The aim of the study was to identify the atypical celiac disease
      (CD) in a cohort of symptomatic osteoporotic patients, younger than 55 years of
      age and 2) To study associated clinical and laboratory features and outcome with
      gluten-free diet. MATERIAL AND METHODS: We studied 33 patients (F:M = 28:5), mean
      age 29 years (range 15-52 years) with osteoporosis (WHO diagnostic criteria, T
      score less than -2.5 on DEXA scan) from January 2000 - June 2002. Serological
      screening for CD was done by detecting circulating IgA antibodies to tissue
      transglutaminase by ELISA. Patients with presence of antibodies to
      transglutaminase were subjected to biopsy from the 2nd part of the duodenum by
      upper GI endoscopy. The biopsies were reported independently by two pathologists
      who were blinded for the serology report. Measurement of mucosal thickness,
      crypts and villi were done with an ocular micrometer. Other parameters like
      complete hemogram, serum iron, total iron binding capacity (TIBC), calcium
      profile, 25-OH-D, parathyroid hormone (PTH) were evaluated. Assessment of
      clinical and laboratory parameters was performed within 4-12 weeks of starting
      gluten-free diet (GFD). RESULTS: Thirteen patients had circulating IgA antibodies
      to transglutaminase. Intestinal biopsies were performed on 11 patients and were
      consistent with the diagnosis of CD (total villous atrophy--two, subtotal villous
      atrophy with crypt hyperplasia--nine). Patients with CD had significant anaemia
      when compared with non-CD osteoporotic patients. Other important observations in
      these 11 patients were low serum calcium and phosphorus, low 25-OH-D, high PTH.
      Significant improvement in clinical and laboratory parameters was noted in all
      patients within 6-12 weeks of starting GFD. CONCLUSION: Symptomatic osteoporotic
      patients (younger than 55 years of age) especially with associated anaemia should
      be investigated for CD. Simple measures like omission of wheat from diet (GFD)
      lead to significant improvement in symptoms within weeks.

PMID- 15266927
TI  - Multiple intracranial granulomas.

PMID- 15266928
TI  - Bacteriophage therapy: an alternative to conventional antibiotics.
AB  - Bacteriophage therapy is an important alternative to antibiotics in the current
      era of multidrug resistant pathogens. We reviewed the studies that dealt with the
      therapeutic use of phages from 1966-1996 and few latest ongoing phage therapy
      projects via internet. Phages were used topically, orally or systemically in
      Polish and Soviet studies. The success rate found in these studies was 80-95%
      with few gastrointeslinal or allergic side effects. British studies also
      demonstrated significant efficacy of phages against Escherichia coli,
      Acinetobacter spp., Pseudomonas spp and Staphylococcus aureus. US studies dealt
      with improving the bioavailability of phage. Problems faced in these studies have
      also been discussed. In conclusion, phage therapy may prove as an important
      alternative to antibiotics for treating multidrug resistant pathogens.

PMID- 15266929
TI  - Thalidomide: an old wine in new bottle.

PMID- 15266930
TI  - Future Medicare system.

PMID- 15266931
TI  - Fatal 2,4-D (ethyl ester) ingestion.
AB  - 2,4-D (2,4-dichlorphenoxyacetic acid) is widely used in agriculture and forestry
      to destroy broad leaved weeds (herbicide). It has a moderate mammalian toxicity
      and human poisoning has rarely been reported except following ingestion with
      suicidal intent. We report two young adults who ingested it with suicidal intent,
      developed neurological, cardiac, hepatic and renal toxicity and died.

PMID- 15266932
TI  - Acute superior mesenteric vein thrombosis associated with factor V 'Leiden' gene
      mutation.
AB  - OBJECTIVES: To study thrombophilia states in Indian patients with acute
      spontaneous superior mesenteric vein thrombosis (SMVT). METHODS: Two men with
      this condition, a 56 year old and a 31 year old presenting with acute SMVT,
      demonstrated on CT scan, were subjected to a thrombophilia screen consisting of
      Protein C, S, antithrombin levels, lupus anticoagulant, anticardiolipin
      antibodies, fibrinogen levels, factor VIII levels, factor V 'Leiden' gene
      mutation, and paroxysmal nocturnal hematuria screen. RESULTS: A thrombophilia
      screen showed factor V 'Leiden' gene mutation (heterozygous) in both cases.
      Additionally, the first patient had high fibrinogen levels and the second high
      factor VIII levels. Both patients are currently on long-term anticoagulation.
      CONCLUSION: Factor V 'Leiden' gene mutation in association with other
      thrombophilic factors may predispose to spontaneous superior mesenteric vein
      thrombosis.

PMID- 15266933
TI  - Cytomegalovirus nasal polyp after renal transplant.
AB  - Infection is a major problem after transplantation. Cytomegalovirus (CMV) is the
      most common viral infection affecting transplant patients. We describe a case of
      CMV infection with rare clinical manifestation in the form of nasal polyp.
      Patient presented 6 weeks following renal transplantation with history of fever
      and stuffy nose. On evaluation he was found to have nasal polyp which was
      excised. Histopathology revealed characteristic CMV inclusion bodies. Patient
      responded to ganciclovir therapy and is presently doing well eighteen months
      after transplantation.

PMID- 15266934
TI  - Modern plague--HIV infection.

PMID- 15266935
TI  - Metrondazole-induced neurotoxicity.
AB  - A 50 year old male with history of prolonged intake of metronidazole for
      treatment of liver abscess developed acute ataxia, disorientation, distal
      symmetrical sensory and proximal motor neuropathy. Patients being treated with
      metronidazole particularly those on high doses for prolonged period should be
      monitored for neurotoxicity.

PMID- 15266936
TI  - Vitamin D deficiency masquerading as pseudohypoparathyroidism type 2.
AB  - A case of antiepileptic-induced vitamin D deficiency, who presented with
      hypocalcemia, hyperphosphatemia with increased tubular reabsorption of phosphate
      mimicking pseudohypoparathyroidism type 2, is reported. He showed remarkable
      improvement with calcium and vitamin D treatment with normalisation of serum
      calcium and phosphate with reestablishment of phosphaturic response.

PMID- 15266937
TI  - Diffuse abdominal lipomatosis.
AB  - We report a 22-year male who developed progressive distension of abdomen,
      clinically diagnosed as ascites. A diagnosis of abdominal lipomatosis was made on
      the basis of CT evidence of excessive fatty tissue in abdominal cavity which was
      confirmed on laparotomy.

PMID- 15266938
TI  - Hemorrhagic pleural effusion due to pleural hemangioma.
AB  - We report a rare case of isolated pleural hemangioma presenting as recurrent,
      haemorrhagic pleural effusion. Chest radiograph and computed tomography of chest
      was suggestive of left apical tumour. Diagnosis of hemangioma was revealed only
      after thoracotomy and excision of the tumour mass.

PMID- 15266939
TI  - Pulmonary arteriovenous fistula presenting as multiple brain abscess.
AB  - Pulmonary arteriovenous fisula is a rare condition in which there is abnormal
      connection between pulmonary arteries and veins. We describe this condition is an
      18-year-old male who presented with cyanosis, clubbing, polycythemia and multiple
      brain abscesses. The patient was diagnosed as pulmonary arteriovenous fistula
      based on CT scan and on pulmonary angiography. The patient had a complete
      recovery after surgical drainage of brain abscess and excision of right upper
      lobe. After one year of follow up, there are no symptoms and there is complete
      reversal of cyanosis and polycythemia.

PMID- 15266940
TI  - Primary antiphospholipid antibody syndrome presenting as venous infarct and deep
      vein thrombosis.
AB  - We report the case of a young lady with primary antiphospholipid antibody
      syndrome, who had two spontaneous abortions and cerebral venous thrombosis and
      subsequently deep vein thrombosis of the leg veins. Three classes of
      antiphospholipid antibodies (IgG, IgM, IgA) were elevated. There was no clinical
      or laboratory evidence for other autoimmune or systemic illnesses. We are
      presenting the case due to the rarity of the same.

PMID- 15266941
TI  - Connective tissue lipoatrophic panniculitis.
AB  - A 23 years old girl with a past history of sero-positive oligoarticular juvenile
      idiopathic arthritis developed nodules and depressed scars over face and limbs.
      Biopsy from the lesion revealed mixed panniculitis. She responded to steroids and
      hydroxychloroquine but has residual lipoatrophic scars needing reconstructive
      surgery.

PMID- 15266942
TI  - Adulteration of drugs of alternative systems of medicine with corticosteroids.

PMID- 15266943
TI  - Importance of ankle jerk in acute flaccid paralysis.

PMID- 15266944
TI  - Selective serotonin reuptake inhibitors-- few pitfalls.

PMID- 15266945
TI  - Falciparum malaria precipitating hyperkalaemic periodic paralysis.

PMID- 15266946
TI  - Ethylenedibromide needs to be banned as food fumigant.

PMID- 15266947
TI  - Periodontal physiology during pregnancy.

PMID- 15266948
TI  - Neuroprotective role of melatonin in oxidative stress vulnerable brain.
AB  - The brain is deficient in oxidative defense mechanisms and hence is at greater
      risk of damage mediated by reactive oxygen species (ROS) resulting in molecular
      and cellular dysfunction. Emerging evidence suggesting the activation of
      glutamate gated cation channels, may be another source of oxidative stress,
      leading to neuronal degeneration. Oxidative stress has been implicated in the
      development of neurodegenerative diseases like Parkinsonism, Alzheimer's disease,
      Huntington's disease, amyotrophic lateral sclerosis, epileptic seizures, and
      stroke. Melatonin, the pineal hormone, acts as a direct free radical scavenger
      and indirect antioxidant. It is suggested that the increase in neurodegenerative
      diseases is attributable to a decrease in the levels of melatonin with age.
      Melatonin has been shown to either stimulate gene expression for the antioxidant
      enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione
      reductase) or to increase their activity. Additionally, it neutralizes hydoxyl
      radical, superoxide radical, peroxyl radical, peroxynitrite anion, singlet
      oxygen, hydrogen peroxide, nitric oxide, and hypochlorous acid. Unlike other
      antioxidants, melatonin can easily cross all morphophysiological barriers, e.g.,
      the blood brain barrier, and enters cells and subcellular compartments. Though
      evidence are accumulating to suggest the potential of melatonin in
      neurodegenerative conditions, much information needs to be generated before the
      drug can find place in neurology clinics.

PMID- 15266949
TI  - Effect of yoga training on handgrip, respiratory pressures and pulmonary
      function.
AB  - Although there are a number of reports on the effect of yoga training on
      pulmonary functions, very few studies have been undertaken on the effect of yoga
      training on respiratory pressures and handgrip endurance. Hence the present work
      was planned to study the effect of yoga training on hand grip strength (HGS),
      hand grip endurance (HGE), maximum expiratory pressure (MEP), maximum inspiratory
      pressure (MIP), forced expiratory volume (FEV), forced expiratory volume in first
      second (FEV1) and peak expiratory flow rate (PEFR). 20 school children in the age
      group of 12 to 15 years were given yoga training (asans and pranayams) for 6
      months. 20 age and gender-matched students formed the control group. Yoga
      training produced statistically significant (P < 0.05) increase in HGS and HGE.
      MEP, MIP, FEV, FEV1 and PEFR also increased significantly (P < 0.001) after the
      yoga training. In contrast, the increase in these parameters in the control group
      was statistically insignificant. Our study shows that yoga training for 6 months
      improves lung function, strength of inspiratory and expiratory muscles as well as
      skeletal muscle strength and endurance. It is suggested that yoga be introduced
      at school level in order to improve physiological functions, overall health and
      performance of students.

PMID- 15266950
TI  - Auditory evoked responses in postmenopausal women on hormone replacement therapy.
AB  - The effect of hormone replacement therapy (HRT) was studied in 32 postmenopausal
      women on their auditory Evoked Potentials i.e. auditory brainstem response (ABR),
      Middle latency response (MLR) & slow vertex response (SVR). Recordings were done
      on computerized evoked potential recorder using 10/20 system of electrode
      placement and standard click stimuli. A significant improvement in neural
      transmission was observed as was evidenced by decrease in the ABR wave latencies
      I, III, IV & V and interpeak latency III-V and I-V after 6 months of HRT. A
      similar significant decrease was observed in MLR wave latencies of Po, Na & Pa.
      The SVR wave latencies although found to be decreased after HRT, could not reach
      the level of statistical significance. There was a significant inverse
      correlation obtained between latencies of wave I in ABR, Po in MLR and serum
      estradiol. The results indicate the effect of sex hormone in improving
      transmission in auditory pathway from periphery through brainstem, thalamus upto
      cortex. However slow vertex responses indicate that auditory association areas
      are not much affected. This might have bearing on improvement of
      neuropsychological functions in postmenopausal women on HRT.

PMID- 15266951
TI  - Effect of 7-nitroindazole alone and in combination with phenobarbitone and
      diazepam on picrotoxin-induced convulsions in rats.
AB  - There are no reports on the effect of 7-nitroindazole (7-NI) on chemically
      induced convulsions. Hence, in the present study, its (100 and 200 mg/kg) action
      was tested alone and in combination with phenobarbitone (20 mg/kg) and diazepam
      (0.25 mg/kg) on picrotoxin (PCT)-induced convulsions in rats. The changes
      produced by 7-NI on nitric oxide synthase (NOS) activity and nitric oxide (NO)
      concentration were determined in the brain. The effect of 7-NI was tested in L
      arginine (1000 mg/kg) pretreated (30 min) animals. The smaller dose (100 mg/kg)
      of 7-NI did not alter NOS activity and NO concentration, but inhibited PCT
      induced convulsions indicating that its anticonvulsant action was devoid of an
      involvement of NO. But, an inhibition of NOS activity, by a larger (200 mg/kg)
      dose of it, resulted in a promotion of the convulsant action of PCT and in an
      impairment of the anticonvulsant effect of both phenobarbitone and diazepam. The
      proconvulsant action of 7-NI was reverted by L-arginine. These results suggest
      that 100 and 200 mg/kg of 7-NI produce distinguishable action on PCT-induced
      convulsions because NOS activity is inhibited by 200 mg/kg and not by 100 mg/kg
      of it. The results further suggest that NO acts as anticonvulsant and that the
      NOS inhibitors, like 7-NI, cannot be used as an anticonvulsant either alone or in
      combination with other anticonvulsants.

PMID- 15266952
TI  - Blocking of enhanced sensitivity to behavioral effects of naloxone induced by
      narcotic agonists in rats.
AB  - The present experiment evaluated whether prior treatment with naloxone could
      block the sensitization to opiate antagonist induced by single dose
      administration of pure agonist (morphine) or mixed agonist (buprenorphine). Food
      deprived male Wistar rats were trained to respond for food on a multiple-trial,
      fixed-interval 3 min schedule. Reinforcement was contingent upon a response
      within a 10-s limited hold period following a fixed-interval of 3 min. A trial
      consisted of three fixed interval of 3 min separated by a 10 min timeout period
      during which responses were not reinforced. The rate decreasing effects of the
      opioid antagonist naloxone was determined by cumulative dosing. Pretreatment with
      morphine (0.3 mg/ kg, SC) and buprenorphine (0.03 mg/kg, SC) resulted in an
      increase sensitivity to the rate decreasing effect of naloxone compared to saline
      pretreatment. Administration of naloxone (0.3 mg/kg) 10 min prior to pretreatment
      doses of buprenorphine (0.03 mg/kg; 1.0 mg/kg) and morphine (0.3 mg/kg) increased
      sensitization to naloxone. However, greater sensitization was observed at low
      dose of buprenorphine. The increased sensitivity was partially blocked at high
      dose of buprenorphine (1.0 mg/ kg) by naloxone pretreatment. These results
      suggest that the doses of naloxone used to block opioid induced sensitization
      might be different from those required in animals with normal sensitivity to
      opioid antagonists. Further agonist-induced sensitization to behavioral effects
      of opioid antagonist appears to be opioid receptor specific.

PMID- 15266953
TI  - Effect of occupational noise on the nocturnal sleep architecture of healthy
      subjects.
AB  - BACKGROUND & OBJECTIVES: Noise is considered to be a non-specific stressor which
      generally causes physiological and psychological effects in an individual. Many
      occupations involve workers being subjected to loud noise levels without adequate
      protective measures. The study was done to document the changes, if any, in the
      nocturnal sleep architecture of healthy persons exposed to loud occupational
      noise during daytime. METHODS: The study was a retrospective cohort design
      wherein three groups of eight subjects each, exposed to continuous occupational
      background noise levels of > 75dB for 1-2 years, 5-10 years and > 15 years were
      selected. Corresponding age and gender matched healthy controls (eight for each
      group) who worked in a quiet atmosphere were also recruited. All night sleep
      polysomnography was done on all subjects. In the morning, subjects rated their
      quality of sleep on a Visual Analogue Scale. RESULTS: There is a strong
      association between occupational exposure to loud noise and poor sleep efficiency
      (Relative Risk 2.49; Confidence Interval 1.12 to 5.57; P = 0.01, Fisher's exact
      test). The group exposed to noise for 1-2 years had a decrease in Total Rapid Eye
      Movement Time, Non Rapid Eye Movement Time, Slow Wave Sleep Time, Sleep Onset
      Latency and Total Sleep Time. The other two groups showed lesser number of
      changes in sleep architecture. Subjectively there was a decrease for sleep
      continuity in Group I and an increase for sleep onset in Group II. There is no
      correlation between loudness of noise in the workplace and sleep efficiency.
      INTERPRETATION AND CONCLUSION: It can be concluded that workers exposed to loud
      background occupational noise are at an increased risk of having poor quality
      sleep but adaptation to this effect probably takes place after a few years.

PMID- 15266954
TI  - Mid latency and slow vertex responses during pregnancy.
AB  - Central auditory pathways picked up electro-physiologically as mid latency
      responses (MLRs) and slow vertex responses (SVRs) have been studied least in
      women during their critical periods of life although auditory brainstem responses
      (ABRs) have been studied by many researchers. In the present study MLRs and SVRs
      were recorded in 20 pregnant women of age group 18-28 years. Their period of
      gestation ranged between 26-40 weeks and pregnancy had been uneventful and
      normal. MLRs and SVRs were recorded from Cz-A1 and Cz-A2 positions with
      alternating 90 dB sound pressure click stimuli delivered at 5 Hz and 0.5 Hz
      respectively. 256 stimuli for mid-latency and 64 stimuli for slow vertex
      responses were averaged and analyzed. Different waves of these auditory evoked
      responses were compared with 20 age matched non-pregnant females. The data
      obtained was analyzed for each variable by using unpaired student's T test.
      Present study did not reveal any difference in MLR waves during pregnancy when
      compared with the non-pregnant females whereas all the SVR waves were found to be
      significantly delayed in pregnant females. As SVR generators are found in
      different cortical areas, it can be said that auditory information processing at
      the higher centers is slow during pregnancy which in turn could be due to
      elevated levels of sex hormones specially estrogen and progesterone during
      pregnancy.

PMID- 15266955
TI  - Influence of habits on masons' blood cholesterol.
AB  - Plasma total cholesterol, HDL cholesterol, glucose and total protein were
      estimated in (male) masons without any habits (normal masons) and masons with
      habits (cigarette smoking, alcohol consumption and betel-quid cum tobacco
      chewing) and compared with normal subjects. Masons had less total cholesterol and
      more HDL cholesterol when compared with normal subjects, which may be due to
      their occupational physical activities. Among masons, cigarette-smoking masons
      alone had more total cholesterol and less HDL cholesterol. Blood glucose also
      decreased in masons and more so in betel-quid cum tobacco chewing masons when
      compared with normal subjects while total protein content showed no variation.

PMID- 15266956
TI  - Hepatoprotective effect of Himoliv, a polyherbal formulation in rats.
AB  - The effect of Himoliv (HV) was evaluated in carbon tetrachloride or paracetamol
      induced hepatotoxicity in rats. Liver necrosis was produced by administering
      single dose of either carbon tetrachloride (CCl4, 1 ml/kg, 50% v/v with olive
      oil, s.c.) or paracetamol (PC, 1 g/kg, p.o.). The liver damage was evidenced by
      elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum
      glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (ALP) and
      hepatic thiobarbituric acid reacting substances (TBARS) and superoxide dismutase
      (SOD). HV pretreatment (0.5 and 1.0 ml/kg, p.o.) significantly (P < 0.001)
      reduced CCl4 or PC-induced elevations of the levels of SGOT, SGPT, ALP and TBARS,
      while the reduced concentration of SOD due to CCl4 or PC was reversed. Silymarin
      (25 mg/ kg, p.o.), a known hepatoprotective drug showed similar results.

PMID- 15266957
TI  - Lipid peroxidation and antioxidant enzymes in gestational diabetics.
AB  - The exact pro-oxidant and antioxidant status in gestational diabetes is still
      unclear. To add new insight to the question, changes in the lipid peroxidation
      products (MDA) and activities of antioxidant enzymes: superoxide dismutase (SOD)
      and catalase in red blood cell hemolysates were evaluated in 20 women with
      gestational diabetes. 20 healthy pregnant women served as the control group.
      Statistical analysis was done using unpaired Student' t - test. Pregnant women
      with gestational diabetes showed an increase in lipoperoxidation products (P <
      0.001) and a decrease in SOD activity (P < 0.01) as compared to normal pregnant
      women while no significant change was observed in catalase activity. These
      findings suggest increased oxidative stress and decreased detoxification or free
      radical scavenging capacity in pregnancy complicated by diabetes.

PMID- 15266958
TI  - Evaluation of vitamin E against deltamethrin toxicity in broiler chicks.
AB  - Deltamethrin toxicity was studied in broilers and vitamin E was evaluated for
      therapeutic management. Day old male broiler chicks were randomly divided into 3
      groups consisting of 6 chicks in each. Group 1 was maintained as control for 6
      wks, group 2 was fed on deltamethrin (100 mg/kg feed) for 6 wks and group 3 was
      fed on deltamethrin for the first 4 wks and during the subsequent 2 wks with
      vitamin E (300 mg/kg feed) with out deltamethrin. Weekly body weights, feed
      conversion ratio, glutathione (GSH) concentration and high density lipoproteins
      (HDL) were significantly (P < 0.05) reduced, while the activities of glutathione
      peroxidase (GSH-Px), glutathione reductase (GSH-R), catalase, aspartate
      aminotransferase (AST) and lactate dehydrogenase (LDH), and the lipid profile and
      renal biomarkers were increased significantly (P < 0.05) in group 2 and 3 at the
      end of 4th wk as compared to group 1. Following treatment with vitamin E during
      the last 2 wks in group 3, all the parameters in study revealed improvement. From
      this study, it is concluded that deltamethrin induces toxicity by oxidative
      damage in biological system and supplementing vitamin E in feed is useful in
      treating accidental toxicity.

PMID- 15266959
TI  - Blood pressure response to cold pressor test in siblings of hypertensives.
AB  - One hundred and five female and thirty-four male student volunteers were divided
      into three groups. Each group was again divided into siblings of hypertensives
      (SH) and siblings of normotensives (C). SH group had higher basal seated and
      supine Systolic and Diastolic Blood Pressures (SBPs and DBPs, respectively).
      During cold pressor test (CPT), the SH group showed higher rise of SBPs and DBPs.
      All the volunteers were again regrouped as hyperreactors (HR) (the criteria of a
      rise of more than 22 mmHg systolic and 18 mmHg diastolic blood pressure during
      (CPT) and normoreactors (NR). HR showed higher resting seated SBPs and DBPs, and
      higher rise of SBPs & DBPs during CPT as compared to control groups. The rise in
      SBPs and DBPs in hyperreactors was significantly higher than SH groups only in 16
      19 years female group. The rise of SBPs and DBPs during CPT were also higher in
      HR as compared to NR of all age groups. The rise of SBPs and DBPs during CPT was
      significantly higher in controls than in NR in the two female groups. The study
      suggests that identification of hyperreactors in population gives a better
      indication of potential hypertensives of future than the children of
      hypertensives.

PMID- 15266960
TI  - Chemopreventive action of Boerhaavia diffusa on DMBA-induced skin carcinogenesis
      in mice.
AB  - Boerhaavia diffusa, Linn (Fam: Nyctagenaceae), is widely used for the treatment
      of Jaundice in various parts of India. In the present study, cancer
      chemopreventive property of B. diffusa was evaluated on 7,12-dimethyl
      benz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice
      (6-7 weeks old). A single topical application of 7,12-dimethyl benz(a)anthracene
      (50 microg/50 microl of acetone), followed 2 weeks later by repeated application
      of croton oil (1% in acetone three times a week) and continued till the end of
      the experiment exhibited 100% tumor incidence. In contrast, mice treated
      topically on the shaven backs with the Boerhaavia diffusa extract at either the
      peri-initiational phase (i.e. 7 days before and 7 days after the application of
      DMBA; Group II), post initiational phase (i.e. from the day of start of croton
      oil treatment and continued till the end of the experiment; Group III) or
      continuously at the peri- and post-initiational stages (i.e. 7 days prior to DMBA
      application and continued till the end of the experiment; Group IV), a
      significant reduction in the values of tumor incidence (Group II - 65%; Group III
      - 30%; Group IV - 25%), average number of tumors per tumor bearing mouse (Group
      II - 2.8; Group III - 0.75; Group IV - 0.35) and papillomas per papilloma bearing
      mouse (Group II - 3.1; Group III - 2.5; Group IV - 1.2) were observed.

PMID- 15266961
TI  - Effect of Ocimum sanctum (OS) leaf extract on hepatotoxicity induced by
      antitubercular drugs in rats.

PMID- 15266962
TI  - Differential effect of cyclooxygenase-2 preferring [correction of prefering]
      inhibitors on electrically- and chemically-induced seizures in mice.

PMID- 15266963
TI  - Thioacetamide toxicity and the lung: histological analysis.

PMID- 15266964
TI  - Antinociceptive activity of seeds of Trigonella foenum gracecum in rats.

PMID- 15266965
TI  - Accumulating Dobzhansky-Muller incompatibilities: reconciling theory and data.
AB  - Theoretical models of the accumulation of Dobzhansky-Muller incompatibilities
      (DMIs) are studied, and in particular, the framework introduced by Orr (1995) and
      a verbal model introduced by Kondrashov et al. (2002). These models embody very
      different assumptions about the relationship between the substitution process
      underlying evolutionary divergence and the formation of incompatibilities. These
      differences have implications for our ability to make inferences about the
      divergence from patterns in the relevant data. With this in mind, the models are
      investigated for their ability to account for three patterns evident in this
      data: (1) the asymmetrical nature of incompatibilities under reciprocal
      introgression; (2) the finding that multiple concurrent introgressions may be
      necessary for an incompatibility to form; and (3) the finding that the
      probability of obtaining an incompatibility by introgressing a single amino acid
      remains roughly constant over a wide range of genetic distances. None of the
      models available in the literature can account for all of the empirical patterns.
      However, modified versions of the models can do so. Ways of discriminating
      between the different models are then discussed.

PMID- 15266966
TI  - Constancy of the G matrix in ecological time.
AB  - The constancy of the genetic variance-covariance matrix (G matrix) across
      environments and populations has been discussed and tested empirically over the
      years but no consensus has so far been reached. In this paper, I present a model
      in which morphological traits develop hierarchically, and individuals differ in
      their resource allocation and acquisition patterns. If the variance in resource
      acquisition is many times larger than the variance in resource allocation then
      strong genetic correlations are expected, and with almost isometric relations
      among traits. As the variation in resource acquisition decreases below a certain
      threshold, the correlations decrease overall and the relations among traits
      become a function of the allocation patterns, and in particular reflecting the
      basal division of allocation. A strong bottleneck can break a pattern of strong
      genetic correlation, but this effect diminishes rapidly with increasing
      bottleneck size. This model helps to understand why some populations change their
      genetic correlations in different environments, whereas others do not, since the
      key factor is the relation between the variances in resource acquisition and
      allocation. If a change in environment does not lead to a change in this ratio,
      no change can be expected, whereas if the ratio is changed substantially then
      major changes can be expected. This model can also help to understand the
      constancy of morphological patterns within larger taxa as a function of constancy
      in resource acquisition patterns over time and environments. When this pattern
      breaks, for example on islands, larger changes can be expected.

PMID- 15266967
TI  - Genetic correlations and the coevolutionary dynamics of three-species systems.
AB  - The majority of species interact with at least several others. We develop simple
      genetic models of coevolution between three species where interactions are
      mediated by quantitative traits. We assume that one of the species has two
      quantitative traits, each of which governs its interaction with one of the other
      two species. We use this model to explore how genetic correlations between the
      two traits in the multivariate species shape the evolutionary dynamics and
      outcomes of three species interactions. Our results suggest that genetic
      correlations are most important when at least one of the interactions is between
      a predator and prey or parasite and host. In these cases, genetic correlations
      between traits lead to a wide variety of novel coevolutionary outcomes and
      dynamics. In particular, genetic correlations can affect the existence and
      stability of coevolutionary equilibrium points, and they can lead to recurrent or
      permanent maladaptation. When the three species interact only as competitors or
      mutualists, however, genetic correlations have no effect on the outcome of
      coevolution. In all cases, our results reveal the surprising conclusion that both
      positive and negative genetic correlations between traits have qualitatively
      identical effects on coevolutionary dynamics.

PMID- 15266968
TI  - Fitness of indirectly transmitted pathogens: restraint and constraint.
AB  - Many pathogens of medical and veterinary importance have obligatory multihost
      life cycles. Yet, theoretical models aiming to predict patterns of pathogen
      reproductive success and the limited empirical data available with which to
      evaluate them, focus on directly transmitted microparasites. Patterns of host
      exploitation and the relative fitness of individual pathogen genotypes throughout
      the different host stages of multihost life cycles have thus remained ignored. We
      examined correlated responses to artificial selection of Schistosoma mansoni
      lines selected for high or low infection intensity in the intermediate host.
      Pathogen fitness in the intermediate host was strongly inversely correlated with
      pathogen fitness in the definitive host. Moreover, high pathogen infection
      intensity was associated with decreased, rather than increased, virulence to its
      intermediate host. These results raise important implications regarding the
      impact of genetic constraints on the maintenance of genetic and phenotypic
      polymorphisms in natural populations, the evolution and coevolution of parasite
      virulence and host specialization, as well as the success of host-directed
      control programs.

PMID- 15266969
TI  - Natural selection and the organ-specific differentiation of HIV-1 V3
      hypervariable region.
AB  - The existence of organ-specific HIV-1 populations within infected hosts has been
      studied for many years; nonetheless results reported by different authors are
      somewhat discrepant. To tackle this problem, we used a population genetics
      approach to analyze previously published data from the V3 hypervariable region of
      the envelope env gene. Our results are compatible with a population subdivision
      by organs in 95% of individuals analyzed at autopsy. In addition, populations
      infecting the nervous system and testicles clearly appear as differentiated
      subsets of the so-called macrophage-tropic variants. Liver and kidney may harbor
      differentiated populations as well. Although it is widely accepted that organ
      compartmentalization arises as a consequence of different selective pressures
      imposed by different organs, a definitive demonstration has not yet been
      provided. Our analysis of the pattern of synonymous and nonsynonymous nucleotide
      substitutions provides evidence supporting this hypothesis, without discarding
      the role of other evolutionary processes. In contrast, positive selection does
      not seem to be the mechanism responsible for the evolution of patient-specific
      sequences.

PMID- 15266970
TI  - Patterns of reproductive isolation in three angiosperm genera.
AB  - Analyses among animal species have found that reproductive isolation increases
      monotonically with genetic distance, evolves more quickly for prezygotic than
      postzygotic traits, and is stronger among sympatric than allopatric species
      pairs. The latter pattern is consistent with expectations under the reinforcement
      hypothesis. To determine whether similar trends are found among plant species,
      patterns of reproductive isolation (postpollination prezygotic, postzygotic, and
      "total" isolation) in three plant genera (Glycine, Silene, Streptanthus) were
      examined using data from previously published artificial hybridization
      experiments. In Silene, all measures of reproductive isolation were positively
      correlated with genetic distance. In contrast, in Glycine and Streptanthus,
      correlations between reproductive isolation and genetic distance were weak or
      nonsignificant, possibly due to the influence of biologically unusual taxa,
      variable evolutionary forces acting in different lineages, or insufficient time
      to accumulate reproductive isolation. There was no evidence that postpollination
      prezygotic reproductive isolation evolved faster than postzygotic isolation in
      Glycine or Silene. We also detected no evidence for faster accumulation of
      postmating prezygotic isolation between sympatric than allopatric species pairs;
      thus we found no evidence for the operation of speciation via reinforcement. In
      Silene, which included six polyploid species, results suggest that changes in
      ploidy disrupt a simple monotonic relationship between isolation and genetic
      distance.

PMID- 15266971
TI  - The evolution of larval morphology and swimming performance in ascidians.
AB  - The complexity of organismal function challenges our ability to understand the
      evolution of animal locomotion. To meet this challenge, we used a combination of
      biomechanics, phylogenetic comparative analyses, and theoretical morphology to
      examine evolutionary changes in body shape and how those changes affected
      swimming performance in ascidian larvae. Results of phylogenetic comparative
      analyses suggest that coloniality evolved at least three times among ascidians
      and that colonial species have a convergent larval morphology characterized by a
      large trunk volume and shorter tail length in proportion to the trunk. To explore
      the functional significance of this evolutionary change, we first verified the
      accuracy of a mathematical model of swimming biomechanics in a solitary (C.
      intestinalis) and a colonial (D. occidentalis) species and then ran numerous
      simulations of the model that varied in tail length and trunk volume. The results
      of these simulations were used to construct landscapes of speed and cost of
      transport predictions within a trunk volume/tail length morphospace. Our results
      suggest that the reduction of proportionate tail length in colonial species
      resulted in improved energetic economy of swimming. The increase in the size of
      larvae with the origin of coloniality facilitated faster swimming with negligible
      energetic cost, but may have required a reduction in adult fecundity. Therefore,
      the evolution of ascidians appears to be influenced by a trade-off between the
      fecundity of the adult stage and the swimming performance of larvae.

PMID- 15266972
TI  - Speciation on the coasts of the new world: phylogeography and the evolution of
      bindin in the sea urchin genus Lytechinus.
AB  - Beginning with E. Mayr's study in 1954, tropical sea urchins have played an
      important role in studies of speciation in the sea, but what are the processes of
      cladogenesis and divergence that give rise to new species in this group? We
      attempt to answer this question in the genus Lytechinus. Unlike the majority of
      other tropical sea urchin genera, which have circumtropical distributions,
      Lytechinus is mostly confined to the tropics and subtropics of the New World. We
      sequenced a region of mitochondrial cytochrome oxidase I and the entire molecule
      of nuclear bindin (a sperm gamete recognition protein) of nearly all species in
      the genus, and we assayed isozymes of three partially sympatric closely related
      species and subspecies. We found that in both mitochondrial DNA (mtDNA) and in
      bindin the genus Lytechinus is paraphyletic, encompassing Sphaerechinus
      granularis as the sister species of L. euerces. The rest of the species are
      arranged in an Atlantic clade composed of L. williamsi and L. variegatus, and a
      Pacific clade containing L. anamesus, L. pictus, L. semituberculatus, and L.
      panamensis. Divergence between these clades suggests that they were separated no
      later than the closure of the Isthmus of Panama, and possibly before this time.
      Our data confirm that L. anamesus and L. pictus from California are a single
      species, and provide no evidence of differentiation between L. variegatus
      variegatus from the Caribbean and L. variegatus atlanticus from Bermuda.
      Lytechinus variegatus variegatus mtDNA is distinct from that of L. variegatus
      carolinus from the North American seaboard and the Gulf of Mexico, whereas their
      bindins are very similar. However, there is clear evidence of introgression of
      mtDNA between the two subspecies and they share alleles in all sampled isozyme
      loci. Lytechinus williamsi from the Caribbean shares mtDNA haplotypes with L.
      variegatus variegatus, and they also share isozymes in all assayed loci. Their
      bindin, however, is distinct and coalesces within each morphospecies. A private
      clade of mtDNA in L. williamsi may be indicative of former differentiation in the
      process of being swamped by introgression, or of recent speciation. Recent sudden
      expansions in effective population size may explain the predominance of a few
      mitochondrial haplotypes common to the two species. Despite the high divergence
      of bindin (relative to differentiation of mtDNA) between L. variegatus and L.
      williamsi, comparison of amino acid replacement to silent substitutions by
      various methods uncovered no evidence for positive selection on the bindin of any
      clade of Lytechinus. With the possible exception of L. williamsi and L.
      variegatus, our results are consistent with a history of allopatric speciation in
      Lytechinus. The molecular results from Lytechinus, along with those of other
      similar studies of sea urchins, suggest that the general speciation patterns
      deduced in the middle of last century by Mayr from morphology and geography have
      held up, but also have uncovered peculiarities in the evolution of each genus.

PMID- 15266973
TI  - No evidence that polyandry benefits females in Drosophila melanogaster.
AB  - Understanding the evolution of polyandry (mating with multiple males) is a major
      issue in the study of animal breeding systems. We examined the adaptive
      significance of polyandry in Drosophila melanogaster, a species with well
      documented costs of mating in which males generally cannot force copulations. We
      found no direct fitness advantages of polyandry. Females that mated with multiple
      males had no greater mean fitness and no different variance in fitness than
      females that mated repeatedly with the same male. Subcomponents of reproductive
      success, including fecundity, egg hatch rate, larval viability, and larval
      development time, also did not differ between polyandrous and monogamous females.
      Polyandry had no affect on progeny sex ratios, suggesting that polyandry does not
      function against costly sex-ratio distorters. We also found no evidence that
      polyandry functions to favor the paternity of males successful in precopulatory
      sexual selection. Experimentally controlled opportunities for precopulatory
      sexual selection had no effect on postcopulatory sperm precedence. Although these
      results were generally negative, they are supported with substantial statistical
      power and they help narrow the list of evolutionary explanations for polyandry in
      an important model species.

PMID- 15266974
TI  - Genetic diversity and disease resistance in leaf-cutting ant societies.
AB  - Multiple mating by females (polyandry) remains hard to explain because, while it
      has substantial costs, clear benefits have remained elusive. The problem is acute
      in the social insects because polyandry is probably particularly costly for
      females and most material benefits of the behavior are unlikely to apply. It has
      been suggested that a fitness benefit may arise from the more genetically diverse
      worker force that a polyandrous queen will produce. One leading hypothesis is
      that the increased genetic diversity of workers will improve a colony's
      resistance to disease. We investigated this hypothesis using a polyandrous leaf
      cutting ant and a virulent fungal parasite as our model system. At high doses of
      the parasite most patrilines within colonies were similarly susceptible, but a
      few showed greater resistance. At a low dose of the parasite there was more
      variation between patrilines in their resistance to the parasite. Such genetic
      variation is a key prerequisite for polyandry to result in increased disease
      resistance of colonies. The relatedness of two hosts did not appear to affect the
      transmission of the parasite between them, but this was most likely because the
      parasite tested was a virulent generalist that is adapted to transmit between
      distantly related hosts. The resistance to the parasite was compared between
      small groups of ants of either high or low genetic diversity. No difference was
      found at high doses of the parasite, but a significant improvement in resistance
      in high genetic diversity groups was found at a low dose of the parasite. That
      there is genetic variation for disease resistance means that there is the
      potential for polyandry to produce more disease-resistant colonies. That this
      genetic variation can improve the resistance of groups even under the limited
      conditions tested suggests that polyandry may indeed produce colonies with
      improved resistance to disease.

PMID- 15266975
TI  - Phenotypic consequences of genetic variation in a gynogenetic complex of Phoxinus
      eos-neogaeus clonal fish (Pisces: Cyprinidae) inhabiting a heterogeneous
      environment.
AB  - We examined the genetic composition, habitat use, and morphological variation of
      a Phoxinus eos-neogaeus unisexual hybrid complex and its sexually reproducing
      progenitor species inhabiting beaver-modified drainages of Voyageurs National
      Park, Minnesota. In addition to the single diploid P. eos-neogaeus gynogenetic
      clone, triploid and diploid-triploid mosaic biotypes were present at our study
      sites. Both P. eos and P. neogaeus, and all three hybrid biotypes were ubiquitous
      throughout one intensively surveyed drainage, but abundances and relative
      frequencies of the parental species and hybrids varied considerably within and
      among successional environments. Data from a large number of additional sites
      indicated that the proportion of polyploid hybrids within an environment was
      negatively related to hybrid relative frequency, implying that the genomic
      constitution of hybrids is an important determinant of clonal fitness among
      successional environments. Statistical comparisons of variation along size-free
      multivariate body shape axes indicated that despite its genetic uniformity, the
      P. eos-neogaeus clone is no less variable than its sexual progenitors, suggesting
      that a single genotype may actually respond to environmental variation with as
      much phenotypic variation as a genetically variable sexual population. The
      incorporation and expression of a third genome in triploid and diploid-triploid
      mosaic biotypes derived from the gynogenetic clone significantly expanded
      phenotypic variation of the clone. This additional variation results in greater
      similarities in habitat use and morphological overlap with the parental species,
      primarily P. eos, the predominant sperm donor for gynogenetic hybrid females in
      this complex. Polyploid augmentation of a diploid gynogenetic clone appears to be
      typical in the P. eos-neogaeus complex, and the additional genetic and phenotypic
      variation that it generates has potentially significant ecological and
      evolutionary consequences for the success and persistence of a single genotype in
      highly variable environments.

PMID- 15266976
TI  - Variable predation regimes predict the evolution of sexual dimorphism in a
      population of threespine stickleback.
AB  - Sexual dimorphism is widespread in nature and can be influenced by sex-specific
      natural selection resulting from ecological differences between the sexes. Here
      we show that contrasting life-history pressures and temporal shifts in ecology
      can exert a strong influence on the evolution of sexual dimorphism. The bony
      spines exhibited by stickleback are a defense against open-water avian predators
      but may be detrimental against benthic macroinvertebrate predators. Female
      stickleback from a coastal lake in western Canada occupy a more open-water
      ecological niche and exhibit greater dorsal and pelvic spine number than males,
      but the magnitude of these differences varies among life-history stages, seasons,
      and years. Ecological data on diet and parasite load and 62 seasonal estimates of
      selection over a 15-year period show that selection favors increased spine number
      in females and decreased spine number in males, but only when pronounced
      ecological differences between the sexes results in differential exposure to the
      two, divergent predation regimes. Thus occasional sex-reversals in ecological
      niche reversed the mode of selection. These processes caused a predictable
      response in the subsequent generation, indicating that divergent predation caused
      evolutionary change in dimorphism. However, temporal oscillations in sex-specific
      selection resulted in no net change in sexual dimorphism over the 15-year study
      period, indicating that fluctuations in directional selection can be responsible
      for long-term stasis. Replicated shifts in selective regime can demonstrate the
      primacy of ecological processes in driving evolution and our results illustrate
      how such shifts are detectable using long-term monitoring of natural populations.

PMID- 15266977
TI  - Environment-dependent admixture dynamics in a tiger salamander hybrid zone.
AB  - After an estimated five million years of independent evolution, the barred tiger
      salamander (Ambystoma tigrinum mavortium) was introduced by bait dealers into the
      native range of the California tiger salamander (A. californiense). Hybridization
      and backcrossing have been occurring in central California for 50-60 years, or an
      estimated 15-30 generations. We studied genetic and ecological factors
      influencing admixture of these two divergent gene pools by analyzing frequencies
      of hybrid genotypes in three kinds of breeding habitats: natural vernal pools,
      ephemeral man-made cattle ponds, and perennial man-made ponds. Perennial ponds
      tended to have higher frequencies of nonnative alleles than either type of
      seasonal pond, even in cases where perennial and seasonal ponds are within a few
      hundred meters. Thus, the hybrid zone has a mosaic structure that depends on pond
      hydrology or ecology. The presence of some broadly acting constraints on
      admixture is suggested by linkage disequilibria between physically unlinked
      molecular markers within ponds. In addition, we found several marker-specific
      deviations from Hardy-Weinberg equilibrium. One marker showed a consistent
      deficit of heterozygotes across pond types. Another showed heterozygote deficits
      only in vernal pools. A third was more likely to have heterozygote excess in
      ephemeral cattle ponds. These patterns indicate that admixture is influenced by
      complex genotype-by-environment interactions.

PMID- 15266978
TI  - The effect of alternative prey on the dynamics of imperfect Batesian and
      Mullerian mimicries.
AB  - Both Batesian and Mullerian mimicries are considered classical evidence of
      natural selection where predation pressure has, at times, created a striking
      similarity between unrelated prey species. Batesian mimicry, in which palatable
      mimics resemble unpalatable aposematic species, is parasitic and only beneficial
      to the mimics. By contrast, in classical Mullerian mimicry the cost of predators'
      avoidance learning is shared between similar unpalatable co-mimics, and therefore
      mimicry benefits all parties. Recent studies using mathematical modeling have
      questioned the dynamics of Mullerian mimicry, suggesting that fitness benefits
      should be calculated in a way similar to Batesian mimicry; that is, according to
      the relative unpalatability difference between co-mimics. Batesian mimicry is
      very sensitive to the availability of alternative prey, but the effects of
      alternative prey for Mullerian dynamics are not known and experiments are rare.
      We designed two experiments to test the effect of alternative prey on imperfect
      Batesian and Mullerian mimicry complexes. When alternative prey were scarce,
      imperfect Batesian mimics were selected out from the population, but abundantly
      available alternative prey relaxed selection against imperfect mimics. Birds
      learned to avoid both Mullerian models and mimics irrespective of the
      availability of alternative prey. However, the rate of avoidance learning of
      models increased when alternative prey were abundant. This experiment suggests
      that the availability of alternative prey affects the dynamics of both Mullerian
      and Batesian mimicry, but in different ways.

PMID- 15266979
TI  - Historical diversification of a terra-firme forest bird superspecies: a
      phylogeographic perspective on the role of different hypotheses of Amazonian
      diversification.
AB  - Among those few hypotheses of Amazonian diversification amenable to falsification
      by phylogenetic and population genetics methods, three can be singled out because
      of their general application to vertebrates: the riverine barrier, the refuge,
      and the Miocene marine incursion hypotheses. I used phylogenetic and population
      genetics methods to reconstruct the diversification history of the upland (terra
      firme) forest superspecies Xiphorhynchus spixii/elegans (Aves: Dendrocolaptidae)
      in Amazonia, and to evaluate predictions of the riverine barrier, refuge, and
      Miocene marine incursion hypotheses. Phylogeographic and population genetics
      analyses of the X. spixiilelegans superspecies indicated that the main prediction
      of the riverine barrier hypothesis (that sister lineages occur across major
      rivers) hold only for populations separated by "clear-water" rivers located on
      the Brazilian shield, in central and eastern Amazonia; in contrast, "white-water"
      rivers located in western Amazonia did not represent areas of primary divergence
      for populations of this superspecies. The main prediction derived from the refuge
      hypothesis (that populations of the X. spixii/elegans superspecies would show
      signs of past population bottlenecks and recent demographic expansions) was
      supported only for populations found in western Amazonia, where paleoecological
      data have failed to support past rainforest fragmentation and expansion of open
      vegetation types; conversely, populations from the eastern and central parts of
      Amazonia, where paleoecological data are consistent with an historical interplay
      between rainforest and open vegetation types, did not show population genetics
      attributes expected under the refuge hypothesis. Phylogeographic and population
      genetics data were consistent with the prediction made by the Miocene marine
      incursion hypothesis that populations of the X. spixii/elegans superspecies found
      on the Brazilian shield were older than populations from other parts of Amazonia.
      In contrast, the phylogeny obtained for lineages of this superspecies falsified
      the predicted monophyly of Brazilian shield populations, as postulated by the
      Miocene marine incursion hypothesis. In general, important predictions of both
      riverine barrier and Miocene marine incursion hypotheses were supported,
      indicating that they are not mutually exclusive; in fact, the data presented
      herein suggest that an interaction among geology, sea level changes, and
      hydrography created opportunities for cladogenesis in the X. spixii/elegans
      superspecies at different temporal and geographical scales.

PMID- 15266980
TI  - Fitness effects of a selfish gene (the Mus t complex) are revealed in an
      ecological context.
AB  - In wild house mice, genes linked to the t transmission distortion complex cause
      meiotic drive by sabotaging wild-type gametes. The t complex is consequently
      inherited at frequencies higher than 90%. Yet, for unclear reasons, in wild mouse
      populations this selfish DNA is found at frequencies much lower than expected.
      Here, we examine selection on the t complex in 10 seminatural populations of wild
      mice based on data from 234 founders and nearly 2000 progeny. Eight of the 10
      populations decreased in t frequency over one generation, and the overall
      frequency of t haplotypes across all 10 populations was 48.5% below expectations
      based on transmission distortion and 34.3% below Mendelian (or Hardy-Weinberg)
      expectations. Behavioral and reproductive data were collected for 10 months for
      each population, and microsatellite genotyping was performed on seven of the
      populations to determine parentage. These combined data show t-associated fitness
      declines in both males and females. This is the first study to show evidence for
      a reduction in the ability of +/t males to maintain territories. Because females
      tend to mate with dominant males, impairment of territorial success can explain
      much of the selection against t observed in our populations. In nature, selection
      against heterozygote carriers of the t complex helps solve the puzzlingly low t
      frequencies found in wild populations. This ecological approach for determining
      fitness consequences of genetic variants has broad application for the discovery
      of gene function in general.

PMID- 15266981
TI  - Ecological genetics of adaptive color polymorphism in pocket mice: geographic
      variation in selected and neutral genes.
AB  - Patterns of geographic variation in phenotype or genotype may provide evidence
      for natural selection. Here, we compare phenotypic variation in color, allele
      frequencies of a pigmentation gene (the melanocortin-1 receptor, Mc1r), and
      patterns of neutral mitochondrial DNA (mtDNA) variation in rock pocket mice
      (Chaetodipus intermedius) across a habitat gradient in southern Arizona. Pocket
      mice inhabiting volcanic lava have dark coats with unbanded, uniformly melanic
      hairs, whereas mice from nearby light-colored granitic rocks have light coats
      with banded hairs. This color polymorphism is a presumed adaptation to avoid
      predation. Previous work has demonstrated that two Mc1r alleles, D and d, differ
      by four amino acids, and are responsible for the color polymorphism: DD and Dd
      genotypes are melanic whereas dd genotypes are light colored. To determine the
      frequency of the two Mc1r allelic classes across the dark-colored lava and
      neighboring light-colored granite, we sequenced the Mc1r gene in 175 individuals
      from a 35-km transect in the Pinacate lava region. We also sequenced two neutral
      mtDNA genes, COIII and ND3, in the same individuals. We found a strong
      correlation between Mc1r allele frequency and habitat color and no correlation
      between mtDNA markers and habitat color. Using estimates of migration from mtDNA
      haplotypes between dark- and light-colored sampling sites and Mc1r allele
      frequencies at each site, we estimated selection coefficients against mismatched
      Mc1r alleles, assuming a simple model of migration-selection balance. Habitat
      dependent selection appears strong but asymmetric: selection is stronger against
      light mice on dark rock than against melanic mice on light rock. Together these
      results suggest that natural selection acts to match pocket mouse coat color to
      substrate color, despite high levels of gene flow between light and melanic
      populations.

PMID- 15266982
TI  - Natural selection drives altitudinal divergence at the albumin locus in deer
      mice, Peromyscus maniculatus.
AB  - In populations that are distributed across steep environmental gradients, the
      potential for local adaptation is largely determined by the spatial scale of
      fitness variation relative to dispersal distance. Since altitudinal gradients are
      generally characterized by dramatic ecological transitions over relatively short
      linear distances, adaptive divergence across such gradients will typically
      require especially strong selection to counterbalance the homogenizing effect of
      gene flow. Here we report the results of a study that was designed to test for
      evidence of adaptive divergence across an altitudinal gradient in a natural
      population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey
      of allozyme variation across a steep altitudinal gradient in the southern Rocky
      Mountains that spanned several distinct biomes, from prairie grassland to alpine
      tundra. As a control for the effects of altitude, we also surveyed the same loci
      in mice sampled along a latitudinal transect through the prairie grassland that
      ran perpendicular to the east-west altitudinal transect. We used a coalescent
      based simulation model to identify loci that deviated from neutral expectations,
      and we then assessed whether locus-specific patterns of variation were nonrandom
      with respect to altitude. Results indicated that the albumin locus (Alb) reflects
      a history of diversifying selection across the altitudinal gradient. This
      conclusion is supported by two main lines of evidence: (1) Alb was characterized
      by levels of divergence across the altitudinal transect that exceeded neutral
      expectations in two consecutive years of sampling (in contrast to the spatial
      pattern of variation across the latitudinal transect), and (2) levels of
      divergence at the Alb locus exhibited a positive association with altitudinal
      distance in both years (in contrast to the pattern observed at unlinked loci). We
      conclude that clinal variation at the Alb locus reflects a balance between gene
      flow and diversifying selection that results from elevational changes in fitness
      rankings among alternative genotypes.

PMID- 15266983
TI  - Climate change and size evolution in an island rodent species: new perspectives
      on the island rule.
AB  - As stated by the island rule, small mammals evolve toward gigantism on islands.
      In addition they are known to evolve faster than their mainland counterparts.
      Body size in island mammals may also be influenced by geographical climatic
      gradients or climatic change through time. We tested the relative effects of
      climate change and isolation on the size of the Japanese rodent Apodemus
      speciosus and calculated evolutionary rates of body size change since the last
      glacial maximum (LGM). Currently A. speciosus populations conform both to
      Bergmann's rule, with an increase in body size with latitude, and to the island
      rule, with larger body sizes on small islands. We also found that fossil
      representatives of A. speciosus are larger than their extant relatives. Our
      estimated evolutionary rates since the LGM show that body size evolution on the
      smaller islands has been less than half as rapid as on Honshu, the mainland-type
      large island of Japan. We conclude that island populations exhibit larger body
      sizes today not because they have evolved toward gigantism, but because their
      evolution toward a smaller size, due to climate warming since the LGM, has been
      decelerated by the island effect. These combined results suggest that evolution
      in Quaternary island small mammals may not have been as fast as expected by the
      island effect because of the counteracting effect of climate change during this
      period.

PMID- 15266984
TI  - Climatic adaptation and the evolution of basal and maximum rates of metabolism in
      rodents.
AB  - Metabolic rate is a key aspect of organismal biology and the identification of
      selective factors that have led to species differences is a major goal of
      evolutionary physiology. We tested whether environmental characteristics and/or
      diet were significant predictors of interspecific variation in rodent metabolic
      rates. Mass-specific basal metabolic rates (BMR) and maximum metabolic rates
      (MMR, measured during cold exposure in a He-O2 atmosphere) were compiled from the
      literature. Maximum (Tmax) and minimum (Tmin) annual mean temperatures, latitude,
      altitude, and precipitation were obtained from field stations close to the
      capture sites reported for each population (N = 57). Diet and all continuous
      valued traits showed statistically significant phylogenetic signal, with the
      exception of mass-corrected MMR and altitude. Therefore, results of phylogenetic
      analyses are emphasized. Body mass was not correlated with absolute latitude, but
      was positively correlated with precipitation in analyses with phylogenetically
      independent contrasts. Conventional multiple regressions that included body mass
      indicated that Tmax (best), Tmin, latitude, and diet were significant additional
      predictors of BMR. However, phylogenetic analyses indicated that latitude was the
      only significant predictor of mass-adjusted BMR (positive partial regression
      coefficient, one-tailed P = 0.0465). Conventional analyses indicated that Tmax,
      Tmin (best), and altitude explained significant amounts of the variation in mass
      adjusted MMR. With body mass and Tmin in the model, no additional variables were
      significant predictors. Phylogenetic contrasts yielded similar results. Both
      conventional and phylogenetic analyses indicated a highly significant positive
      correlation between residual BMR and MMR (as has also been reported for birds),
      which is consistent with a key assumption of the aerobic capacity model for the
      evolution of vertebrate energetics (assuming that MMR and exercise-induced
      maximal oxygen consumption are positively functionally related). Our results
      support the hypothesis that variation in environmental factors leads to variation
      in the selective regime for metabolic rates of rodents. However, the causes of a
      positive association between BMR and latitude remain obscure. Moreover, an
      important area for future research will be experiments in all taxa are raised
      under common conditions to allow definitive tests of climatic adaptation in
      endotherm metabolic rates and to elucidate the extent of adaptive phenotypic
      plasticity.

PMID- 15266985
TI  - Calibration age and quartet divergence date estimation.
AB  - The date of a single divergence point--between living alligators and crocodiles-
      was estimated with quartet dating using calibrations of widely divergent ages.
      For five mitochondrial sequence datasets, there is a clear relationship between
      calibration age and quartet estimate--quartets based on two relatively recent
      calibrations support younger divergence estimates than do quartets based on two
      older calibrations. Some of the estimates supported by young quartets are
      impossibly young and exclude the first appearance of the group in the fossil
      record as too old. The older estimates--those based on two relatively old
      calibrations--may be overestimates, and those based on one old and one recent
      calibration support divergence estimates very close to fossil data. This suggests
      that quartet dating methods may be most effective when calibrations are applied
      from different parts of a clade's history.

PMID- 15266986
TI  - Sexual conflict and sexual selection: lost in the chase.
AB  - The emergent field of evolutionary biology that studies disparities between the
      evolutionary interests of alleles expressed in the two sexes, or sexual conflict,
      promises to offer novel insights into male-female coevolution and speciation. Our
      theoretical understanding of basic concepts is, however, still incomplete. In a
      recent perspective paper, Pizzari and Snook provided a framework for
      understanding sexually antagonistic coevolution and for distinguishing this
      process from other models of male-female coevolution and suggested an
      experimental protocol to test for sexually antagonistic coevolution. Here, I show
      that the framework is flawed, primarily because it is built upon the mistaken
      assumption that male and female fitness can evolve independently. Further, while
      the empirical strategy advocated has indeed offered important insights in the
      past, it does not allow unambiguous discrimination between competing hypotheses.

PMID- 15266987
TI  - Habitat fragmentation and biodiversity: testing for the evolutionary effects of
      refugia.
AB  - Concordant areas of endemism among taxa have important implications both for
      understanding mechanisms of speciation and for framing conservation priorities.
      Here we discuss the need for careful testing of phylogeographic data for evidence
      of such concordance, with particular reference to the Indonesian island of
      Sulawesi. This is because there are good reasons to question whether concordance
      between taxa is likely to be a common pattern, and because of the serious
      implications of incorrectly concluding that the biodiversity of a given area can
      be partitioned in this way.

PMID- 15266988
TI  - Anorexia and bulimia in the family.

PMID- 15266989
TI  - Budesonide and formoterol in a single inhaler controls asthma in adolescents.
AB  - Despite the availability of effective treatments and national guidelines,
      morbidity from asthma remains high among adolescents. Adolescents need to be
      considered as a distinct group of individuals with different requirements to
      those of children and adults. In particular, their non-adherence to prescribed
      treatment regimens is of concern and is a significant factor contributing to the
      high rate of morbidity in adolescents. Studies in children aged 4 to 17 years
      suggest that the combination of an inhaled corticosteroid (ICS) and a long-acting
      beta2-agonist effectively controls asthma symptoms in patients who remain
      symptomatic on ICS alone. In order to improve adherence to therapy, the use of
      combined therapy with an ICS and a long-acting beta2-agonist in a single inhaler
      should be considered and the dosing frequency should be adjusted according to the
      severity of asthma symptoms. This should empower patients with a greater degree
      of self-management and may be important in helping adolescents feel responsible
      for the management of their asthma. Results from a recent subanalysis demonstrate
      that the combination of budesonide and formoterol administered twice daily via a
      single inhaler (Symbicort Turbuhaler) rapidly gains and maintains control of
      asthma in adolescents whose asthma is not controlled on ICS alone. It is
      anticipated that this will lead to improved adherence to therapy in this
      difficult-to-treat population.

PMID- 15266990
TI  - Application, effectiveness, and limitations of the electrophysiological diagnosis
      of neurotoxic effects of chronic environmental mycotoxins in humans.
AB  - An extensive body of data demonstrates that diverse groups of mycotoxins can
      alter the structure and function of the nervous system in a variety of ways with
      notable human health consequences. Myconeurotoxicity refers to any adverse
      effects of exposure to mycotoxins or byproducts of primary and secondary mold
      metabolism, including volatile organic compounds (VOCs) on the structural or
      functional integrity of the developing or adult nervous system. Neuromycotoxic
      effects may involve a spectrum of biochemical, morphological, behavioral, and
      physiological abnormalities whose onset can vary from immediate to delayed
      action, following exposure to a mycotoxin, and whose duration may be transient or
      persistent and result in disability, while some may have life-threatening
      consequences. Myconeurotoxicity may result from effects of the mycotoxins acting
      directly on the elements of the nervous system or acting on other biological
      systems, which then adversely affect the nervous system. This paper reviews the
      application, effectiveness, and limitations of the electrophysiological diagnosis
      of myconeurotoxic effects of chronic environmental exposure to mycotoxins. The
      systemic targets of mycotoxic effects were reviewed for greater understanding as
      to why different neurophysiological test techniques have different levels of
      outcomes. Thus, nerve conduction velocity, sensory, motor, and evoked potentials,
      electroencephalographic techniques were evaluated using previously published
      papers and our clinical experience. Although, neuromycotoxic disorders can be
      established using clinical electrophysiological diagnosis, there is always the
      possibility of false positive and false negative results in some patients, which
      may be due to a multi-factorial etiopathogenesis of neuromycotoxicity. Detection
      of nervous system toxicity and other measures of toxicity could be achieved using
      a combination of these neurodiagnostic techniques.

PMID- 15266991
TI  - Health impacts of frequent heavy automobile traffic on children and adolescents.
AB  - This paper assesses the extent to which particulate, elemental and organic carbon
      emissions from heavy traffic in urban city roads affect the health of children
      and the adolescent health. Although the health effects of exposures may be
      cumulative, it is in the adolescence that the manifestations are realized. This
      paper therefore, assesses the best way forward for monitoring and preventing the
      environmental health impacts of heavy traffic on children and adolescents who
      live within the vicinity of urban city transportation systems. Major urban cities
      such as Houston, New York, and California are cited as examples of cities where
      health-related problems have already been reported. The particulate, elemental
      and organic carbon emissions are reviewed as the sources by which heavy traffic
      and the hazardous chemical emissions affect the health of the populace. The role
      of accessory loading and engine speed on idling emissions in direct health risks
      of children and adolescents is evaluated. The association of particulate,
      elemental, and organic carbon emission with respiratory effects (including,
      allergies and asthma), and the related behavior problems in children and the
      adolescents are discussed. The best strategies in preventing the effects of heavy
      traffic in the urban cities are suggested by introducing new effective monitoring
      techniques and exposure assessment methods. It is visualized that a more
      comprehensive research is needed to develop robust regulatory systems that would
      control the efficiency of automobiles and prevent the adverse health effects
      relating to heavy traffics in urban city roads. Strong city environmental health
      authorities-community partnerships relevant to exposure information should be
      encouraged.

PMID- 15266992
TI  - Nutritional rehabilitation of anorexia nervosa. Goals and dangers.
AB  - Nutritional rehabilitation of adolescents with anorexia nervosa is both a science
      and an art. The goals are to promote metabolic recovery; restore a healthy body
      weight; reverse the medical complications of the disorder and to improve eating
      behaviors and psychological functioning. Most, but not all of the medical
      complications are reversible with nutritional rehabilitation. Refeeding patients
      with anorexia nervosa results in deposition of lean body mass initially, followed
      by restoration of adipose tissue as treatment goal weight is approached. The
      major danger of nutritional rehabilitation is the refeeding syndrome,
      characterized by fluid and electrolyte, cardiac, hematological and neurological
      complications, the most serious of which is sudden unexpected death. The
      refeeding syndrome is most likely to occur in those who are severely
      malnourished. In such patients, this complication can be avoided by slow
      refeeding with careful monitoring of body weight, heart rate and rhythm and serum
      electrolytes, especially serum phosphorus. This paper reviews our clinical
      experience.

PMID- 15266993
TI  - "Non-engaged" young people in Hong Kong: key statistics and observations.
AB  - This paper reports the key statistics and observations regarding "non-engaged"
      adolescents in Hong Kong, where "non-engaged" adolescents refer to unemployed
      young people and adolescents who do not pursue any further studies in the 15-24
      year age bracket. Several phenomena could be highlighted from the available
      statistics on non-engaged young people in Hong Kong. First, there was a rise in
      adolescent unemployment figures, particularly in the 1990s. Second, youth
      unemployment rates for adolescents aged 15-24 years were higher than the overall
      unemployment rates for the general population. Third, while youth unemployment
      rates in Hong Kong were lower than those reported in some English-speaking
      countries, the figures were higher than those reported in Mainland China. Fourth,
      some demographic correlates of youth non-engagement were found: a) unemployment
      rates were relatively higher in younger adolescents than in older adolescents; b)
      the sex ratios (number of males per 1,000 females) in non-engaged young people
      were higher than those of young people in the general population; c) the
      educational attainment of non-engaged young people was lower than that of the
      same age group in the general population; d) new arrival status was not related
      to youth non-engagement. Fifth, some family correlates were also observed: a)
      compared with adolescents who were not non-engaged youths, there was higher
      proportion of non-engaged youths living with one parent; b) the educational
      attainment of parents of non-engaged youths and the family income of their
      families were lower than those of households without non-engaged youths.

PMID- 15266994
TI  - Predictors of sexual involvement among adolescents in rural Jamaica.
AB  - Early sexual activity of adolescents is associated with increased risk of teenage
      pregnancy, sexually transmitted infections including HIV, and higher
      maternal/perinatal morbidity and mortality. HIV and adolescent pregnancy are
      among the most serious public health problems in Jamaica. The objective of this
      study was to identify the potential predictors of adolescent sexual activity in
      Jamaica. A cross-sectional survey was conducted among 788 students 13-19 years of
      age in Jamaica. A questionnaire containing items on socio-demographic
      characteristics such as age and gender, and scales on adolescent values about
      sexual activity, self-efficacy for abstinence, parental love, and depression were
      administered to adolescents at secondary schools in the parish of Hanover.
      Reliability analysis of the scales, descriptive statistics, and logistic
      regression to determine predictors of sexual activity were conducted.
      Approximately 62% of adolescents who responded reported previous sexual
      intercourse and 38% reported never having had sex. The mean age for sexual debut
      was 13.6 years. Logistic regression revealed delay values (values towards
      delaying sexual activity) as protective (OR=0.16, CI=0.09-0.26) against
      involvement in sexual activity. Risk factors for sexual activity included being
      older (OR=1.9, CI=1.50-2.50), being male (OR=2.26, CI=1.39-3.68) and having grown
      up values (OR=1.49, CI=1.05-2.12). Contrary to expectations, having higher self
      efficacy skills was predictive (OR=1.47, CI=1.05-2.05) of adolescent sexual
      involvement. Analyses by gender revealed that delay and grownup values predicted
      male sexual activity, while self-efficacy, paternal love and delay values
      predicted female behavior. These findings show the importance of age, gender,
      self-efficacy, delay and grown-up values in predicting sexual activity in
      adolescents and indicate the need for gender-specific interventions for Jamaican
      adolescents.

PMID- 15266995
TI  - Atypical neuroleptic malignant syndrome associated with risperidone treatment in
      two adolescents.
AB  - Neuroleptic Malignant Syndrome (NMS) is a known, life threatening, side effect of
      classical antipsychotic drugs. We report two cases of 16 and 17 year old males,
      who suffered life-threatening "NMS-Like" syndromes in association with
      Risperidone treatment. Further controlled studies are needed.

PMID- 15266996
TI  - Coagulation disorders as the cause of menorrhagia in adolescents.
AB  - This study was undertaken to assess the frequency of coagulation disorders as a
      cause of menorrhagia in adolescents. A retrospective chart review was conducted
      of all adolescents with menorrhagia admitted to the Adolescent Unit of Ihsan
      Dogramaci Childrens Hospital of Hacettepe University Faculty of Medicine in
      Ankara, Turkey from May 1999 to April 2002. 47 admissions for menorrhagia were
      identified, 44 were dysfunctional uterine bleeding due to anovulation, while a
      primary coagulation disorder was found in three patients. Two had Von Willebrand
      disease and one factor 11 deficiency. We suggest that pediatricians,
      gynecologists and other adolescent health care providers should be aware of the
      primary coagulopathy as a cause of menorrhagia in adolescence.

PMID- 15266997
TI  - Trends in adolescent asthma in Israel.
AB  - There has been observed a worldwide increase in childhood asthma and this short
      communication reviews current research on adolescent asthma in Israel. Several
      studies have found an overall asthma prevalence of 7.8% for Jewish children, 4.9%
      for Arab children and 3.7% for the total population, while 7.8% was found in
      Bedouin children in the south of Israel. For the 1980-1997 period for the 5-34
      year age group the AMR (asthma mortality rate) per 100,000 was found to be 0.226
      with no significant difference between Jews and Arabs. This is a decrease as a
      result of increase in the use of inhaled corticosteroids (ICS) and a better anti
      inflammatory treatment.

PMID- 15266998
TI  - Biological and molecular characterization of Besnoitia akodoni n.sp. (Protozoa:
      Apicomplexa) from the rodent Akodon montensis in Brazil.
AB  - The diversity among coccidian parasites of the genus Besnoitia is incompletely
      known. Of the eight currently described members of the genus, only B. jellisoni
      is known to parasitize a rodent host. Here, we propose a new name, Besnoitia
      akodoni, for the species initially isolated form the rodent Akodon montensis in
      Brazil. The tissue cysts of B. akodoni were up to 442 microm in diameter and
      bradyzoites were 8.4 x 1.4 microm in size. The bradyzoites contained enigmatic
      bodies, micronemes and rhoptries. Tachyzoites were 5.8 x 1.5 microm in size and
      they could be grown in vitro in bovine monocytes and African Green monkey cells
      where they divided by endodyogeny. Besnoitia akodoni was infective to laboratory
      raised mice (Mus musculus) and gerbils (Meriones unguiculatus) but not to cats
      (Felis catus). Comparison of the conserved sequences of the small subunit rDNA
      clearly established the close relationship of B. akodoni with other members of
      the genus. However, sequences of the more variable first internal transcribed
      spacer portion of the ribosomal DNA repeat support its differentiation from the
      other species of the genus.

PMID- 15266999
TI  - Transfusional Mansonella perstans microfilariasis.
AB  - Mansonella perstans filariasis is widely distributed across the center of Africa
      and equatorial America. We describe a case of post-transfusional M. perstans
      microfilariasis in a young child, affected with severe Plasmodium falciparum
      malaria, admitted in Goundi Hospital in South of Chad. A decrease of M. perstans
      microfilariasis in the patient's blood was observed, with no subsequent
      development of either clinical symptoms or eosinophilia. We suggest that, in
      endemic areas, transfused M. perstans microfilariae may be cleared from the blood
      over relatively short periods of time. It is likely that only adult worms are
      responsible for symptoms and eosinophilia, whereas microfilariae in the
      bloodstream are unable to give clinical manifestations.

PMID- 15267000
TI  - Helminths in Leuciscus cephalus from the river Adda, Lombardy, Northern Italy.
AB  - Chubs (Leuciscus cephalus) were caught at various locations along the river Adda
      and from Lake of Como (Lombardy, Northern Italy) and endoparasitic helminths were
      studied in order to integrate the knowledge on distribution of helminth fauna of
      chubs in Lombardy and to investigate on the structure of its parasite
      infracommunities with respect to different habitat typologies. The following
      species of parasites were isolated: Pomphorynchus laevis, Allocreadium
      markewitschi, Parasymphylodora markewitschi, Raphidascaris acus, Hysterothylacium
      aduncum and Molnaria intestinalis. P laevis resulted the most common species (P =
      56.52%). The mean abundances and the prevalence of helminths were different in
      chubs according to the sampling site. The mean abundances were lower in chubs
      sampled in the lake than those sampled in the river. Particularly, P. laevis
      showed the highest prevalences in fish captured in the river sites. The
      trematodes (P. markewitschi and A. markewitschi) seem to be more related with
      "lake" typology. These results are discussed and related to differences in life
      cycle of these parasites and to other factors like sampling period and the
      conditions of the aquatic sites that could influence the richness of parasite
      species.

PMID- 15267001
TI  - Canine filariosis in Umbria: an update of the occurrence one year after the first
      observation of autochthonous foci.
AB  - Following the first observation of two autochthonous foci of canine filariosis
      occurred in Umbria region in the year 2001, a survey on prevalence and risk
      factors was conducted 12 months later to better understand the actual entity of
      the Dirofilaria problem in Umbria region. Blood samples were collected between
      January and December 2002 from 2406 dogs living in a total of 7 towns located in
      the identified areas at risk. Blood samples were tested by a modified Knott's
      technique to evaluate the microfilaraemia and, by a commercial ELISA kit, to
      detect in the sera adult antigens of D. immitis. The results were subject to
      statistical analysis. A total of 439 dogs were found to be infected. The true
      prevalence (LC 95%) was of 18%. Microfilariae of D. immitis were detected in 286
      dogs (13%) while 112 dogs (6%) showed only microfilariae of D. repens and 41 dogs
      (1.6%) microfilariae of both D. immitis and D. repens. The prevalence ratio (PR)
      for each species of Dirofilaria (LC 95%) calculated in association with different
      risk factors (age, sex, use, outdoor night status, position, living together with
      other dogs, breed) and the statistical significance between the risk factors and
      the presence/absence of the infection, evaluated for each species of Dirofilaria,
      are discussed.

PMID- 15267002
TI  - A stable focus of canine leishmaniosis in the Bologna Province, Italy.
AB  - During an epidemiological survey carried out for two consecutive years (2001
      2002), autochthonous cases of canine leishmaniosis (CanL) were reported in
      Communes of the Bologna Province (Emilia-Romagna Region, northern Italy),
      involved in the past (1971-1972) in a severe outbreak of human visceral
      leishmaniosis (VL). Serological controls, carried out by immunofluorescence
      antibody test on a sample of owned dogs, detected a mean prevalence of 2.5% in
      the first year in 4 Communes, and of 11.2% in the second year in only one
      Commune, where an incidence value of 9.3% was assessed. The autochthonous origin
      of the infection was confirmed in 11 out of 13 positive animals in the first year
      and in 5 out of 6 new cases in the second year. In one case the parasitological
      examinations led to the isolation of leishmaniae characterized as Leishmania
      infantum zymodeme MON 1. Entomological surveys carried out during two sandfly
      seasons in one of the areas concerned by the VL outbreak showed the presence of
      Phlebotomus perfiliewi and, to a lesser extent, of P perniciosus, both proven
      vectors of L. infantum in Italy. The results obtained seem to suggest the
      presence of a stable focus of CanL in the territory involved in the previous VL
      outbreak of 1971-1972, within which the infection in the canine population had
      been assessed only serologically. Such an epidemiological situation may be seen
      either as the persistence of an old focus or as a new imported one.

PMID- 15267004
TI  - [Aedes albopictus (Diptera: Culicidae) in Rome: experimental study of relevant
      control strategy parameters].
AB  - Since 1997, Aedes albopictus has colonised and then rapidly invaded the city of
      Rome (Italy) and its peripheral areas. Presently, the control of this mosquito in
      Italy relies mainly on larvicidal treatment of street storm sewer catch basins
      with the organophosphate temephos. We have therefore obtained baseline data on
      the susceptibility to temephos of the Roman Ae. albopictus population by
      laboratory bioassays on F1 fourth-instar larvae following standard WHO protocols.
      Estimated lethal concentrations were 0.014 mg/l (LC50) and 0.022 mg/l (LC90)
      indicating a lack of resistance to this compound. The persistence of temephos in
      sewer catch basins was evaluated by follow-up of catch basins treated with a dose
      of 1.5 mg of active ingredient. Mosquito larvae were recovered in 10% and 50% of
      the treated basins at 9 and 18 days posttreatment, respectively. In order to
      understand the relative contribution of this larval habitat to adult populations,
      we conducted a survey in the Zoo of Rome to estimate the larval density of
      mosquitoes breeding in sewer catch basins. A complete census of a 16.5 ha area
      mapped 243 catch basins, but only 25 (10.3%) contained water; of the latter 8
      (32.0%) hosted mosquito larvae. All positive catch basins contained larvae of
      Culex pipiens, which were associated with Culiseta longiareolata and/or Ae.
      albopictus in 6 and 3 cases, respectively. A longitudinal survey of one catch
      basin over 4 months showed that the mean larval density of Ae. albopictus was
      markedly lower than that of Cx pipiens and Cs. Iongiareolata, ranging between 0
      and 1.3 larvae/dip as compared to 0-33.2 and 0-22.7 larvae/dip, respectively.
      However, adult densities of Ae. albopictus in this area estimated during the same
      period with 20 ovitraps showed consistently high values (proportion of positive
      ovitraps around 100%). These preliminary observations suggest that whenever
      alternative larval biotopes other than sewer catch basins are widely available,
      they might be more productive and/or preferred substrates to catch basins for Ae.
      albopictus breeding.

PMID- 15267003
TI  - Ultrastructural evidence of the degenerative events occurring during
      embryogenesis of the filarial nematode Brugia pahangi after tetracycline
      treatment.
AB  - Intracellular bacteria belonging to the genus Wolbachia have been described in
      filarial nematodes and these microorganisms appear to have evolved an obligatory
      mutualistic association with their filarial hosts. In fact, antibiotic treatment
      leads to the clearance of bacteria from worms resulting in a block in
      embryogenesis and, eventually, death of adult filariae. Currently, the
      antifilarial action of antibiotic treatment is interpreted as a secondary
      consequence of the bacteriostatic activity against Wolbachia endosymbionts. Here,
      we demonstrate by transmission electron microscopy the degenerative events
      occurring during embryogenesis of Brugia pahangi after tetracycline treatment.
      After 56 days of treatment the cytoplasm of hypodermal cords was totally void of
      Wolbachia and numerous vacuoles, residual of cytolitic activity, were observed.
      In the ovary, the morphology of the oocytes was well conserved 33 days after
      treatment, but the texture of symbiotic bacteria appeared altered. After 56 days
      of treatment embryogenesis was dramatically affected and the terminal portion of
      the ovary appeared totally empty. The authors suggest that the symbiotic bacteria
      play a direct role in worm metabolism and a long-term bacteriostatic effect may
      block bacterial activity involved in the active control of cytolysis. As a
      consequence, the bacteriophorous vacuole is transformed into a digestive vacuole
      and the whole symbiotic population is disrupted.

PMID- 15267005
TI  - Sandfly (Diptera, Psychodidae, Phlebotominae) fauna of South-Western Pakistan. 1.
      Diagnostic morphology of Phlebotomus papatasi (Scopoli), Ph. bergeroti (Parrot)
      and Ph. salehi (Mesghali).
AB  - A survey was conducted to study the morphology of the sandfly fauna in South
      Western Pakistan (Balochistan). During the revision of different genera of
      sandflies the specimens of Phlebotomus papatasi (Scopoli) (N = 720), Ph.
      bergeroti Parrot (N = 30) and Ph. salehi Mesghali (N = 70) were encountered in
      various localities. These localities appear to be new records of the subgenus in
      the literature to date. Ph. bergeroti is reported for the first time from
      Pakistan and Ph. salehi from Balochistan as well. Characters of these three
      Pakistanese Phlebotomus are compared with the published data of these species
      from other countries. Keys for the identification of Pakistanese Phlebotomus are
      also constructed. Two female Ph. papatasi collected from indoors out of 132
      female flies (1.5%) were found positive with flagellate infection in pharynx and
      midgut. The possible vectorial role of these flies is also discussed. Further
      surveys are necessary in parts of the country that have not been systematically
      surveyed.

PMID- 15267006
TI  - What is the best hydration regimen to prevent contrast media-induced
      nephrotoxicity?
AB  - BACKGROUND: Hydration is a commonly used method to prevent the decline in GFR
      after contrast media (CM) application. So far, there have been no controlled,
      randomized trials investigating the most effective route of fluid administration.
      METHODS: Thirty-nine patients with normal renal function (65 +/- 9 years, serum
      creatinine 0.9 +/- 0.2 mg/dl, GFR = 110 +/- 31 ml/min/1.73 m2) receiving at least
      80 ml of low-osmolality CM during an angiographic procedure were randomized to
      one of the following hydration regimens: Group 1: volume expansion with 300 ml
      saline during CM administration (n = 20, serum creatinine 0.8 +/- 0.1 mg/dl, GFR
      119 +/- 27 ml/min/1.73 m2); Group 2: intravenous administration of at least 2,000
      ml saline within 12 h before and after CM application (n = 19, serum creatinine
      0.9 +/- 0.2 mg/dl, GFR 101 +/- 32 ml/min/1.73 m2). GFR was measured by CM
      clearance (Renalyzer) at baseline and 48 hours after CM administration. The
      primary end point was the mean change in the GFR after 48 hours, the secondary
      one was the incidence of CM-induced nephropathy (CMIN), defined as a decrease in
      GFR of more than 50% from the baseline GFR within 48 hours. RESULTS: Patients of
      group 1 showed a significantly (p < 0.05) higher decline in GFR (delta GFR 34.6
      +/- 25.7 ml/min/1.73 m2) compared to patients receiving the intravenous
      prehydration regimen (delta GFR 18.3 +/- 25.0 ml/min/1.73 m2). The incidence of
      CMIN was lower in prehydrated patients (5.3%) compared to the other group (15%).
      CONCLUSION: In patients with normal renal function, intravenous prehydration
      seems to be a very effective and feasible method to prevent the decline in GFR
      after contrast media exposure. Volume expansion given only during the CM exposure
      appears not to be sufficient enough to prevent renal damage.

PMID- 15267007
TI  - Benign prostatic hyperplasia (BPH) requiring transurethral resection in freshly
      transplanted renal allograft recipients.
AB  - With recent progress in surgery and immunosuppression, more and more older men
      receive a kidney transplant. Thus, it is likely that the incidence of BPH in male
      transplant recipients is growing in parallel with age. Nonetheless, no data exist
      about diagnostic parameters for BPH in freshly transplanted male kidney allograft
      recipients. We evaluated whether established diagnostic and therapeutic criteria
      for BPH are valid for the evaluation of renal transplant recipients. BPH was
      diagnosed in 8 of 11 recipients older than 55 years. In all freshly transplanted
      renal allograft recipients, lower urinary tract symptoms (LUTS) were detected
      using an international prostate symptoms score (IPSS). This score was 9.6 +/- 7.1
      in patients without BPH, and significantly higher with 21.1 +/- 4.3 in patients
      with BPH. In receiver-operating characteristics (ROC) curve analysis a cut-off of
      15.5 was calculated to distinguish best between BPH and non-BPH giving an
      accuracy of 90.2%. Acute urinary retention (AUR) was the predominant sign, which
      occurred in all BPH patients but only in 6.9% in non-BPH patients. Bladder outlet
      obstruction (BOO) was also common with a reduced uroflow with 9.5 +/- 2.2 ml/sec
      in non-BPH and 3.0 +/- 1.8 ml/sec in BPH (8/11 BPH-patients developed AUR prior
      to measurement). By digital rectal examinations, benign prostate enlargement was
      estimated as minimal in 10 of 11 cases of BPH. In urethrocystoscopy kissing lobes
      were detected in all cases of BPH. Since medical treatment with alpha-receptor
      antagonists was not successful, a surgical procedure using a transurethral
      resection was performed without any complications in all cases. Symptoms did not
      recur after resection, and BOO improved with increased uroflow measurements with
      12.3 +/- 4.8 ml/sec 8 days after resection. We conclude that LUTS and BOO are
      common in freshly transplanted renal allograft recipients. The sudden onset of
      outlet obstruction without the potentiality of adaptation of urinary bladder may
      effect lower urinary tract symptoms and bladder outlet obstruction. We conclude
      that an elevated IPSS over 15.5 in combination with AUR and typical
      urethrocystoscopy results are the best methods to diagnose BPH. Conversely, our
      results indicate that uroflowmetry and digital rectal examination are neither
      sensitive nor specific. In addition, once BPH has been diagnosed and treatment
      with receptor antagonists does not relieve urinary tract symptoms, surgical
      resection should be considered.

PMID- 15267008
TI  - Risk factors for peptic ulcer disease in renal transplant patients--11 years of
      experience from a single center.
AB  - BACKGROUND: Peptic ulcer disease is a common complication among renal transplant
      recipients and causes significant morbidity and mortality. METHODS: From 1990
      through 2000, 465 renal transplant patients were followed-up in our institute.
      Most patients received corticosteroids and cyclosporine-based immunosuppressive
      regimen. About one third (n = 156) of them received mycophenolate mofetil.
      Patients with endoscopy-proved peptic ulcer disease were identified by reviewing
      medical records. Possible risk factors were analyzed by univariate analysis and
      multiple logistic regression analysis. RESULTS: Among 465 kidney transplant
      patients, there were 181 (38.9%) who suffered at least 1 episode of peptic ulcer
      disease. The most frequent types of peptic ulcer disease were gastritis, gastric
      ulcer, duodenal ulcer, esophagitis, duodenitis and esophageal ulcer. By
      multivariate analysis, the use of methylprednisolone pulse therapy (odds ratio =
      3.954, 95% confidence interval = 3.154-18.312, p = 0.03) and history of pre
      transplant peptic ulcer disease (odds ratio = 7.599, 95% CI = 1.211-12.905, p <
      0.0001) were independent risk factors for posttransplant peptic ulcer disease.
      CONCLUSIONS: Our findings demonstrated that renal transplant patients who undergo
      methylprednisolone pulse therapy for acute rejection or who have a history of pre
      transplant peptic ulcer disease carry a high risk for the development of peptic
      ulcer disease and deserve intensive antiulcer treatment.

PMID- 15267009
TI  - Dialysis membrane-dependent removal of middle molecules during hemodiafiltration:
      the beta2-microglobulin/albumin relationship.
AB  - AIM: Current hemodialysis therapy modalities such as online hemodiafiltration
      (HDF) attempt to enhance solute removal over a wide molecular weight range
      through a combination of diffusion and convection. While the effects of
      variations of treatment modalities and conditions have been studied reasonably
      well, few studies have examined the efficacy of HDF to remove middle molecules in
      relation to the dialyzer and membrane characteristics. In this investigation,
      diverse high-flux dialyzers, covering a wide range of membrane permeabilities,
      were compared under identical in vivo conditions to assess their ability to
      eliminate larger uremic retention solutes (using beta2-microglobulin as a
      surrogate of middle molecules) without simultaneously causing excessive leakage
      of useful proteins such as albumin. PATIENTS AND METHODS: In a prospective,
      crossover study, 3 ESRD patients were treated with 8 different brands of high
      flux dialyzers at 4 different ultrafiltration (UF)/substitution flow rates (QS:
      0, 30, 60, 90 ml/min) in post-dilution HDF mode. Thus, each patient underwent 32
      treatment sessions, with a total of 96 treatment sessions conducted during the
      entire clinical study. Albumin and beta2-microglobulin levels were measured in
      both, dialysate and blood. Both, albumin and beta2-microglobulin elimination was
      dependent upon the permeability of the dialysis membrane as well as on the
      ultrafiltration/substitution flow rates applied. RESULTS: At the maximum UF rate
      of 90 ml/min, the total albumin loss (measured in the dialysate) ranged from 300
      mg/4 h (for the FLX-15 GWS dialyzers) to 7,000 mg/4 h (for the BS-1.3U
      dialyzers). Up to 50% reduction of albumin occurred within the first 30 minutes
      of the dialysis treatment, and the leakage of albumin increased exponentially
      with increasing UF rates as well as increasing transmembrane pressure (TMP). The
      various dialyzers could be classified according to their UFR-dependent beta2-m
      reduction rates (RR), into low (< 50%; FLX-15 GWS, CT 150G), medium (50-70%;
      Polyflux 14 S, BLS 814SD, H4) and high (> 70%; BS-1.3U, APS 650, FX 60) removers
      of middle molecules. One dialyzer type (CT 150G) showed extremely low beta2-m RR
      and relatively high albumin losses. Most membranes, however, showed either low
      albumin leakage coupled with low beta2-m removal, or high beta2-m RR but at the
      expense of considerable albumin leakage. Only 2 membrane types approached the
      desired balance between high to medium beta2-m RR while simultaneously
      restricting the albumin leakage especially at higher filtration/substitution
      rates. CONCLUSION: Our investigations demonstrate that not all dialysis membranes
      classified as "high-flux" are comparable in their ability to specifically and
      efficiently remove middle molecules, or curtail the unwanted excessive leakage of
      essential proteins from the patient's blood. Thus, the selection of appropriate
      high-flux dialyzers for specific patient requirements should be based more upon
      clinical evaluations and analyses rather than on product specifications alone.

PMID- 15267010
TI  - Hemodialysis for patients bleeding or at risk for bleeding, can be simple, safe
      and efficient.
AB  - AIM: Hemodialysis for patients bleeding or at risk for bleeding requires special
      modalities of treatment that are difficult to perform without potential side
      effects. A simple, safe and adequate method may be applied. METHODS: A modified
      way of extracorporeal circuit preparation, which focuses on minimizing the blood
      air interface and negligible saline flushing of 50 ml/h, is applied for a maximum
      of 3-hour session with routine (not one-to-one) nursing attendance. Data from
      16,954 sessions performed with patients bleeding or at risk for bleeding (15,730
      retrospectively and 1,224 prospectively collected) were analyzed. RESULTS:
      Cumulative failure of treatment, as defined by clotting of the extracorporeal
      circuit requiring termination of the procedure or replacement of the clotted
      part, was not more than 5% as expected for anticoagulation-free hemodialysis. For
      the prospectively recorded sessions, blood flow was 234 +/- 30 ml/min with less
      than 250 ml/min in 42.4% of the sessions. Native blood access was used in 426
      (34.8%), double-lumen catheter in 798 (65.2%), 42 were isolated ultrafiltration
      sessions and 64 blood, 21 plasma, 9 platelet units were transfused. Post/pre urea
      ratio was 0.50 +/- 0.12. Logistic regression showed that among the following:
      duration of the session, type of dialysis, ultrafiltration rate, hematocrit,
      number of platelets, serum total protein, transfusions, blood flow and type of
      access, only blood flow significantly affected failure incidence (coefficient B =
      -0.041, exp(B) = 0.96, p = 0.04). No complications due to treatment were noted.
      CONCLUSION: In patients with active, or at risk for, bleeding, hemodialysis
      without systemic anticoagulation can be adequately and safely performed almost as
      a routine session.

PMID- 15267011
TI  - Managing metabolic complications of peritoneal dialysis.
AB  - AIMS: The purposes of this paper are: to report our experience employing a
      comprehensive, multifaceted treatment program to improve the metabolic
      disturbances of dyslipidemia, hyperglycemia and weight gain observed in our
      peritoneal dialysis patients, and by post-hoc analysis to demonstrate how the
      routine clinical lipid profile can be manipulated arithmetically to estimate
      levels of atherogenic low-density lipids and thereby achieve a more sophisticated
      clinical analysis of dyslipidemia and its response to therapy. METHODS: Data are
      reported for 56 patients who were stable on peritoneal dialysis for at least 6
      months and who had metabolic data available prior to beginning peritoneal
      dialysis. Metabolic complications of peritoneal dialysis were treated by a
      comprehensive strategy involving diet, glycemic control and lipid-lowering
      medications with an emphasis on weight control and exercise. From the measured
      lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and
      triglyceride (TG)), levels of atherogenic low-density lipids (low-density
      lipoprotein (LDL), non-HDL, very-low-density lipoprotein (VLDL) and intermediate
      low-density lipoprotein (IDL) were calculated. RESULTS: Before initiation of
      peritoneal dialysis therapy, the most common lipid abnormalities were low levels
      of HDL (59%) and elevated levels of triglyceride (41%) with infrequent elevations
      of total cholesterol (9%) and low-density lipoprotein (23%). After initiation of
      peritoneal dialysis therapy, all lipid levels, except HDL, increased
      significantly, and hyperlipidemia, hyperglycemia and obesity, singly or in
      combination, occurred in 84% of patients. With treatment, elevated lipid levels
      decreased significantly with reversal of the adverse cardiovascular risk profile
      of lipids that developed during peritoneal dialysis therapy, and HDL levels
      increased significantly. On peritoneal dialysis therapy, all diabetic patients
      required insulin, and glycemic control was achieved in most patients (79%).
      Excessive weight gain (10-24% body weight) occurred in 20% of peritoneal dialysis
      patients. Diabetic patients had a higher incidence of being overweight and obese.
      Post-hoc analysis revealed that levels of VLDL and IDL frequently were elevated
      both before (57-61%) and during (68-84%) peritoneal dialysis and that target
      levels of these atherogenic low-density lipoproteins infrequently (22-26%) were
      achieved. CONCLUSIONS: The metabolic complications of peritoneal dialysis are
      responsive to a comprehensive treatment strategy. Controlling weight gain on
      peritoneal dialysis therapy maybe a difficult challenge for some patients,
      particularly those who are diabetic. Patients with renal failure and on dialysis,
      especially peritoneal dialysis, frequently have elevated levels of the
      atherogenic lipoproteins fragments VLDL and IDL. Future clinical trials should
      focus on the efficacy and safety of aggressive therapy to achieve target levels
      of these atherogenic lipids.

PMID- 15267012
TI  - Increasing the placement of native veins arteriovenous fistulae--the role of
      access surgeons' education and profiling.
AB  - BACKGROUND: The utilization of native veins arteriovenous (AV) fistulae in the US
      remains low despite their superiority over other types of hemodialysis access.
      METHODS: A nephrologist-driven, quality improvement project that concentrated on
      access surgeons was utilized to increase fistulae placement. Period I of the
      project (1998-2000) entailed surgeons' education about advantages of fistulae and
      methods to increase their placement. During period II (2001-2002), referral
      patterns to surgeons were altered according to their performance, and surgeons
      out of the area were utilized. Data on patient characteristics, type of access
      placed and access complications were measured. RESULTS: Fistulae constituted 45%
      of AV access placed in period I and 79% of those placed in period II. Fistulae
      prevalence, which was 15% at the end of the pre-project period, increased to 27%
      at the end of period I and 49% at the end of period II. All changes were
      statistically significant. Complication rates did not increase. Fistulae
      placement by surgeons operating in both periods increased in period II. The
      distribution of types of access placed and outcomes differed significantly among
      surgeons. CONCLUSIONS: Fistulae placement could be increased when the
      nephrologist works with access surgeons and monitors their performance. Profiling
      of access surgeons by policy-makers could be a useful method for the
      identification of surgeons with better skill.

PMID- 15267013
TI  - Tacrolimus- (FK 506) based immunosuppression in severe systemic lupus
      erythematosus.
AB  - In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on
      the presence of 8 out of 11 ARA criteria. Disease onset was acute and included
      renal function impairment with biopsy-proven lupus nephritis (WHO class IV)
      requiring renal replacement therapy. Although conventional immunosuppressive
      therapy regimens proved effective in controlling disease activity, all of the
      administered drugs were accompanied by serious side effects: bilateral femur head
      necrosis with corticosteroids, allergic skin reaction in response to
      azathioprine, nephrotoxicity with cyclosporine, nausea and abdominal pain with
      mycophenolate mofetil and life-threatening septicemia with cyclophosphamide
      treatment. In search for alternative treatment options, tacrolimus (FK506, trough
      serum levels 3-6 ng/ml) was started. FK506 was well-tolerated and lupus activity
      completely resolved within 7 months after initiation of therapy. During 36 months
      of follow-up no arthritic complaints occurred and renal function stabilized at a
      serum creatinine of 2.1 mg/dl with negative anti-ds-DNA antibodies and ANA
      titers. In conclusion, FK506 may be considered as alternative immunosuppressive
      for maintenance treatment in patients with severe lupus erythematosus and side
      effects to conventional regimens.

PMID- 15267014
TI  - Life-threatening Dobrava hantavirus infection with unusually extended pulmonary
      involvement.
AB  - In Europe, hantavirus infections usually present as hemorrhagic fever with renal
      syndrome and its mild form nephropathia epidemica, while clinical cases with
      severe pulmonary affections are extremely rare and appear to be confined to
      infections by New World hanta viruses in the Americas. We report on a female
      patient from Northern Germany, who suffered primarily from severe acute
      respiratory distress syndrome-like pulmonary failure due to Dobrava hantavirus
      infection that was complicated by acute renal insufficiency.

PMID- 15267015
TI  - Always look beyond the stones: hyperoxaluria overlooked.
AB  - We report a case which demonstrates the disastrous consequences of late diagnosis
      of hyperoxaluria in a 24-year-old woman with nephrocalcinosis, a staghorn
      calculus and recurrent urinary tract infections. Her initial management at
      another hospital included multiple percutaneous nephrostomies and lithropsies.
      Metabolic screening was not undertaken. Hyperoxaluria was finally diagnosed by
      elevated urine oxalate (1.235 mmol/24 h) and renal biopsy, by which time there
      was already significant reduction of renal function. A diagnosis of hyperoxaluria
      type I was confirmed by liver biopsy. Despite starting pyridoxine and
      crystallization inhibitors, her renal function deteriorated, requiring
      hemodialysis and she was referred for combined liver-renal transplantation.
      Clinical clues of primary hyperoxaluria type I are a positive family history or
      presentation with severe renal stones at an unusually early age. Irrespective of
      the above, all patients with first presentation of renal calculi should undergo
      metabolic screening, including urine oxalate.

PMID- 15267016
TI  - Nutcracker syndrome associated with severe anemia and mild proteinuria.
AB  - A 70-year-old man was referred to our hospital with the chief complaint of gross
      hematuria. Urinalysis revealed gross hematuria (3+, RBC 100/HPF or more) and mild
      proteinuria (3+, 1.8 g/day) with no urinary casts. Computed tomography of the
      abdomen showed compression of the left renal vein between the superior mesenteric
      artery and the aorta. Ultrasonography showed an increased flow velocity at the
      stenotic portion of the left renal vein. An aortography and selective left renal
      arteriography showed that there was no evidence of tumor vessels or arterial
      abnormalities in the arterial phase. However, the venous phase revealed a
      stenosis of the left renal vein just lateral to the aorta as well as a reflux of
      contrast material toward the left gonadal vein which was dilated. In addition,
      cystoscopy revealed left ureteral bleeding. Based on these findings, we made the
      diagnosis of gross hematuria caused by nutcracker syndrome (NCS). We concluded
      that the main cause of the anemia and proteinuria in our patient was leakage of
      blood and this is confirmed by the relationship of red blood cells to protein in
      the urine because we proved whole blood and plasma protein loss in the urine by
      calculation. Fourteen months after discharge, both the gross hematuria and
      proteinuria spontaneously disappeared. This case strongly suggested that the
      first therapy for hematuria and proteinuria with NCS should be observation.

PMID- 15267017
TI  - Trichosporon asahii infection of a dialysis PTFE arteriovenous graft.
AB  - Trichosporon species are the causative agents of superficial skin infections,
      such as white piedra. Immunocompromised hosts, particularly those with underlying
      hematological malignancy, are at risk of developing invasive infection, which
      usually progresses to disseminated life-threatening disease. Peritonitis caused
      by Trichosporon has been described in end-stage renal disease patients treated
      with continuous ambulatory peritoneal dialysis. Here, we report on a Trichosporon
      infection of an arteriovenous graft in a patient on chronic hemodialysis. The
      infection was successfully treated with fluconazole and total surgical resection
      of the graft.

PMID- 15267018
TI  - Challenges in establishing a clinically and scientifically robust epoetin policy.

PMID- 15267019
TI  - No evidence for a role of SLC7A10 in 19q13 in the etiology of cystinuria.

PMID- 15267020
TI  - Treatment of idiopathic retroperitoneal fibrosis with combined administration of
      corticosteroids and tamoxifen.

PMID- 15267021
TI  - Change is difficult, but necessary.

PMID- 15267022
TI  - Take a card.

PMID- 15267023
TI  - Will the sun set? Legislative review of licensing boards could produce
      substantial change.

PMID- 15267024
TI  - The Stark truth. Government tries to make sense of long and complex law.

PMID- 15267025
TI  - Doctor to doctor: the HIPAA glitch.

PMID- 15267026
TI  - Got a match? Lawsuit could throw residency match into chaos.

PMID- 15267027
TI  - Clearing the confusion. Physicians turn attention to low health literacy
      concerns.

PMID- 15267028
TI  - County hospitals and regional medical care in Texas: an analysis of out-of-county
      costs.
AB  - The current system of regional medical service delivery in Texas places large
      demands on the state's urban public hospitals. To assess the nature and scope of
      such demands, we examined financial data from five of the state's largest public
      hospital districts. During fiscal year 2002, these hospitals reported 103,381
      encounters with out-of-county patients, resulting in 66 million dollars in
      unreimbursed costs. Given the current economic outlook, Texas requires a more
      effective regional model that centralizes tertiary care, disperses primary and
      secondary care, and preserves key public health goods.

PMID- 15267029
TI  - Risk assessment practices of Texas private practitioners for sexually transmitted
      diseases.
AB  - This study describes the sexually transmitted disease (STD) risk assessment
      practices of a sample of private primary care practitioners in Texas. Elicitation
      of sexual history was not universal when these clinicians took the health history
      of their patients. Only 40% of the practices reported conducting a risk
      assessment for STD with all of their patients. In general, practices in
      obstetrics and gynecology, physicians providing care for persons infected with
      human immunodeficiency virus, and female physicians were more likely to indicate
      that they assess all of their patients for risks of STD. More than 90% of the
      practitioners conduct risk assessment for STD with all of those patients
      perceived to be at risk, but the criteria used for determining those patients
      vary greatly among practitioners. Private physicians in Texas provide care for a
      large proportion of individuals afflicted with STDs; our findings raise concerns
      about the lack of uniformity in the process of identifying patients at risk for
      STD.

PMID- 15267030
TI  - Today's shortage: tomorrow's leadership crisis?

PMID- 15267031
TI  - Clinicians' views on reproductive needs and services for teens with negative
      pregnancy tests.
AB  - ISSUES AND PURPOSE: To explore services available to adolescent girls at the time
      of the negative pregnancy test (NPT) in an urban community. DESIGN AND METHODS:
      Clinician focus groups were conducted to identify the needs of adolescents at the
      time of a NPT result. RESULTS: Teens access care in a variety of ways, services
      provided at the time of a NPT were agency and clinician dependent, and strategies
      for follow-up care often were unstructured. Few services were available for
      parents or partners. Barriers included difficulty communicating with agencies,
      lack of staff trained to work with adolescents, and time/financial constraints.
      CONCLUSION: Adolescents need comprehensive, teen-friendly reproductive care at
      the time of a NPT result.

PMID- 15267032
TI  - Impoverished children with asthma: a pilot study of urban healthcare access.
AB  - ISSUES AND PURPOSE: Using Andersen's Behavioral Model of Health Care Use, this
      pilot study was conducted to better understand the experiences of children with
      asthma as they access an urban healthcare system. DESIGN AND METHODS: This
      descriptive study used a convenience sample of 34 families of pediatric asthma
      patients who participated in semistructured interviews and closed medical record
      review. RESULTS: Only one patient reported having a written exacerbation
      management plan. Beliefs regarding medication addiction and side effects were
      frequently reported as barriers to medication adherence, and children seeking
      asthma care in primary care settings saw many care providers. PRACTICE
      IMPLICATIONS: Exploring how expanded nursing roles can help address both family
      and system factors serving as barriers to health care ought to be a key priority
      for nursing.

PMID- 15267033
TI  - Liver transplantation in children: maternal and family stress, coping, and
      adaptation.
AB  - ISSUES AND PURPOSE: This study examined the relationship of family stress,
      severity of the stressor, uncertainty, coping, and family adaptation from
      pretransplantation to posttransplantation. DESIGN AND METHODS: A descriptive,
      longitudinal study of 15 mothers whose children were at least 5 years
      posttransplantation. RESULTS: Maternal stress, coping, and uncertainty
      demonstrated significant changes over time, whereas family stress did not.
      Pretransplantation family stress, anger, and confusion were related to poorer
      family adaptation. PRACTICE IMPLICATIONS: Interventions for mothers
      pretransplantation should account for the coping, levels of stress, and
      uncertainty present at each phase of the transplantation process. Interventions
      need to be tailored to the transplantation phase. Long-term interventions remain
      necessary and should be directed at reinforcement of teaching, as well as
      assessment and provision of parental support relevant to the long-term needs of
      the family.

PMID- 15267034
TI  - Body piercing: issues in adolescent health.

PMID- 15267035
TI  - How to read a research article.

PMID- 15267036
TI  - The debate over combination drug policy for malaria: it may not just be the
      patients' temperatures which need to be brought down.

PMID- 15267037
TI  - Pharmacokinetics of artesunate following oral and rectal administration in
      healthy Sudanese volunteers.
AB  - The aims of this study were to determine the pharmacokinetic parameters of a
      single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to
      suggest a rational dosage regimen for rectal administration. The study design was
      a randomized open cross-over study of 12 healthy volunteers; the analytical
      method used was a reversed phase high performance liquid chromatography with post
      column derivatization and subsequent ultraviolet detection. Pharmacokinetic
      parameters were derived from the main metabolite alpha-dihydroartemisinin data
      due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin
      following oral administration of artesunate had a significantly higher AUC(0
      infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1))
      and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax
      (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was
      no statistically significant difference in the elimination half-life between both
      routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative
      bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9
      (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with
      rectal artesunate is proposed.

PMID- 15267038
TI  - Reference values for peak expiratory flow rate in adults of African descent.
AB  - Substantial racial differences in the values of peak expiratory flow (PEF) rate
      have been noted by several workers in the past. It has also been noted that
      applying prediction formulae derived from a Caucasian population overestimated
      the PEF values in Black Africans by 12%-15%. Yet reference values used up until
      the present, even among Black populations, are based on such formulae. This study
      provides new reference values for use in the Black population. They were obtained
      by using curvilinear formulae derived from the study of 1009 normal adult
      Nigerians (668 men and 341 women) between the ages of 15 years and 82 years,
      living and/or working in Port Harcourt, Nigeria and its hinterland.

PMID- 15267039
TI  - Using body diagrams and disease protocols as part of an integrated approach to
      the medical consultation in Nepal.
AB  - Neither medical assistants nor doctors in Nepal receive adequate training in
      medical consultation techniques. Patients often leave the consultation with poor
      understanding of their disease. Moreover, disease management counselling and
      preventative health counselling are rarely done. In order to address these
      issues, simple body diagrams and disease protocols were developed and tested in a
      random cohort survey of 300 outpatients. While 72% of patients who were shown a
      body diagram achieved basic understanding of their disease, only 38% of patients
      who were not shown a body diagram understood their disease. This improvement was
      significant and independent of other factors. Satisfactory disease management
      counselling was given in 38% of cases, and preventative health counselling in
      36%. There was correlation between use of body diagrams and provision of disease
      management counselling and preventative health counselling. These findings
      emphasize the need for simple consultation tools such as body diagrams and
      disease management protocols in developing countries.

PMID- 15267040
TI  - Stroke subtypes in Black Tanzanians: a retrospective study of computerized
      tomography scan diagnoses at Muhimbili National Hospital, Dar es Salaam.
AB  - Limited data are available on the stroke subtypes in Tanzania and sub-Saharan
      Africa. The present study was aimed at determining retrospectively the pattern of
      confirmed strokes in all patients in our hospital who had been given a
      computerized tomography (CT) brain scan during the study period (April 2001 to
      May 2002). Over the 12-month period 371 CT brain scans were taken, of which 148
      showed stroke, 89 (60.1%) showed haemorrhage and 59 (39.9%) showed infarcts
      (P<0.05). Among the haemorrhagic group 48 (53.9%) were men and 41 (46.1%) women,
      while 31 (52.5%) men and 28 (47.5%) women had infarction. We concluded that there
      were relatively more cases of cerebral haemorrhage than infarction. Hypertension
      and diabetes mellitus were common risk factors in both subtypes of stroke.

PMID- 15267041
TI  - Histological spectrum of chronic hepatitis in precore mutants and wild-type
      hepatitis B virus infection.
AB  - This study compares the histology of liver biopsies in precore mutant (PCM) and
      wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of
      wild-type HBV infection were included. Patients were diagnosed on the basis of
      serological profile and HBV DNA assessment. Liver biopsies in each case were
      assessed for histological activity and stage of fibrosis using a modification of
      Knodell's scoring system. There was no statistically significant (P=0.14)
      difference in histological activity in the two groups. The difference in stage of
      fibrosis in the two groups was statistically significant (P=0.001). Quantitative
      estimation of viral load did not show any correlation with liver histology. PCM
      HBV showed greater stage of fibrosis compared with wild-type infection, and this
      may be related to disease progression and lack of response to therapy.

PMID- 15267042
TI  - Androgens in childhood acquired aplastic anaemia in Chandigarh, India.
AB  - This study assessed the efficacy of stanozolol in acquired aplastic anaemia (AA)
      in children, who were unable to opt for alternative therapies due to financial
      constraints. It uses a retrospective case-record analysis. Medical records of
      children with AA who received stanozolol were analysed. Their clinical and
      haematological profile was studied and the outcome assessed. Forty-nine children
      with acquired AA received stanozolol (1 mg/kg/day) in the period between January
      1991 and December 2000. The median age at diagnosis was 9 years (range: 1.5-13).
      Thirteen (26.5%) defaulted therapy after periods of 1-4 weeks and 11 (22.4%) died
      within 2 months of starting treatment. Ten (20.4%) responded, whilst 15 (30.6%)
      did not. None of the patients with very severe AA responded, two (28.6%) with
      severe AA responded and eight (38%) with non-severe AA had a response. All
      responses were partial except one. Median time taken to respond was 11 weeks
      (range: 1-20). Responders were treated for a median duration of 25 weeks (range:
      13-155), and they were followed-up for a median duration of 25 months (range: 3
      144). Eight (80%) responders were off drugs for a median duration of 18 months
      (range: 6-110). Stanazolol is ineffective for severe and very severe AA. As it
      induced remission in 38% of our patients with non-severe AA, it can be tried in
      this group if other methods of treatment are unaffordable or have failed. A short
      history of presentation (< 3 months) and > or = 70% lymphoid cells in marrow
      correlated with poor prognosis.

PMID- 15267043
TI  - Anchored tubular sheath: a safe technique to prevent hydatid spillage.

PMID- 15267044
TI  - Urine examination for calculogenic crystals in renal stone patients--a newer
      approach using refrigeration.

PMID- 15267045
TI  - Alarming levels of hepatitis B virus detected among rural Tibetans.

PMID- 15267046
TI  - Assessment of information status, behaviours and perception of risk of AIDS in
      rural Gabon.

PMID- 15267048
TI  - Pattern of intraocular pressure in epidemic dropsy in India.
AB  - This study was conducted to report on the intraocular pressure (IOP) pattern in
      patients with epidemic dropsy. Two hundred and thirty proven cases of epidemic
      dropsy were sent for ocular examination. We measured IOP by applanation tonometry
      at different intervals. Patients were followed up until 24 weeks. Intraocular
      pressure of more than 22 mm of Hg was detected in 10.86% patients at the start of
      the study. However, at 12 weeks only 0.43% patients needed medication for control
      of IOP. None required medication for IOP control after 20 weeks. The rise of IOP
      in this case series of epidemic dropsy appeared to be a transient phenomenon and
      drugs needed to be titrated on a weekly basis.

PMID- 15267049
TI  - Day-case adenotonsillectomy: suitable in the tropics?
AB  - This study evaluates the outcome of offering day-case adenotonsillectomy in a
      hospital in the tropics. Seventy-seven patients with adenotonsillitis requiring
      surgery were admitted, operated upon and discharged within 12 h and were also
      evaluated for complications. There were no complications severe enough to warrant
      readmission. Day-case adenotonsillectomy is safe and acceptable in a developing
      country.

PMID- 15267047
TI  - Prevalence of HIV-positives and hepatitis B surface antigen-positives among
      donors in the University of Benin Teaching Hospital, Nigeria.
AB  - The purpose of this study is to determine the rate of human immunodeficiency
      virus (HIV) and hepatitis B surface antigen (HBsAg) among commercial blood donors
      in the University of Benin Teaching Hospital. Five thousand seven hundred and
      thirty-seven prospective commercial blood donors were screened for both HIVand
      HBsAg. Three hundred and eighty-three (7%) donors were positive for HIV while 609
      donors (11%) were positive for HBsAg. Thirty-seven donors were positive for both
      HIV and HBsAg. The need to make the screening of blood donors for HIV and HBsAg
      compulsory in all hospitals is crucial so that the spread of HIV and HBsAg can be
      prevented.

PMID- 15267050
TI  - Maternal and neonatal profile and immediate outcome in extremely low birth weight
      babies in Delhi.
AB  - We studied the maternal and neonatal profile and outcome of extremely low birth
      weight (ELBW) babies at the level III neonatal intensive care unit (NICU) in
      Delhi. Case records of ELBW inborn babies delivered between August 2000 and
      August 2001 were analysed by using a pre-set proforma. A total of 52 ELBW babies
      were admitted to the NICU in the relevant period, of whom 30 (57%) survived.
      Maternal anaemia, previous preterm delivery and pregnancy-induced hypertension
      (PIH) were the common predisposing factors for preterm delivery. Mean gestational
      age was 27.8 weeks and mean birth weight was 831 g. The highest mortality (55%)
      was seen in babies with 26-28 weeks'gestation and those in the birth weight
      category of < 800 g. Neonatal hyperbilirubinaemia (78%) and hyaline membrane
      disease/respiratory distress syndrome (65%) were the most common causes of
      morbidity. A total of 25 babies were mechanically ventilated while 24 (46%)
      received total parenteral nutrition. Sepsis, pulmonary haemorrhage, intracranial
      haemorrhage and necrotizing enterocolitis accounted for the deaths in the study
      population. Retinopathy of prematurity screening was performed in 35 babies
      (68%), of whom 22 were found to be normal. According to the International
      Classification of Retinopathy of Prematurity, most babies (72%) had involvement
      of zone 3 and stage I (63%). The incidence was highest in 26-28 weeks'gestation
      babies (71%) and the < 800 g birth weight category (62%). Maternal risk factors
      such as anaemia and PIH commonly predispose to preterm delivery. There is an
      alarmingly high mortality in this population. Effective steps are required not
      only to avoid extreme prematurity but also to reduce morbidity and mortality of
      all newborns weighing <1000 g at birth.

PMID- 15267051
TI  - Primary small bowel volvulus in Nepal.
AB  - Small bowel volvulus is a rare cause of intestinal obstruction. Primary small
      bowel volvulus occurs without any predisposing cause. It is rare in Western
      countries but common in Africa and Asia. It is the most common cause of bowel
      obstruction in Nepal (excluding incarcerated external hernias). Early diagnosis
      and management is essential to avoid infarction of bowel. Persistent central
      abdominal pain is characteristic. There is no single specific diagnostic clinical
      sign or abnormality in laboratory or radiological findings. There is no role of
      conservative management and, in suspected cases, early laparotomy should be done
      to avoid bowel infarction. In follow-up patients may present with stricture
      formation or recurrence of bowel volvulus.

PMID- 15267053
TI  - Uterine fibroid in a man: how African tradition solved a social crisis.

PMID- 15267052
TI  - Abdominal echinococcosis during pregnancy: clinical aspects and management of a
      series of cases in Chile.
AB  - Twelve pregnant women with hydatid disease are presented with median age of 29;
      11 (91.7%) had a liver cyst and one (8.3%) had a kidney cyst as the primary
      disease location. Four (33.3%) had additional cysts located in the pelvis,
      peritoneal cavity and/or spleen; eight (66.7%) had two or more abdominal cysts.
      Three patients (25.0%) had surgery at the 3rd month after delivery and nine
      (75.0%) during their pregnancy. There was no histological evidence of hydatid
      disease in placentas, and no serological evidence of echinococcosis in the
      newborns was confirmed. One patient died after surgery. After a mean follow-up
      time of 39.5 months, we found one recurrent case of pelvic hydatid disease.
      Management of abdominal echinococcosis during pregnancy is an uncommon and
      difficult problem owing to the serious potential risks for mother and child.

PMID- 15267054
TI  - Retrobulbar neuritis following rabies vaccination.

PMID- 15267055
TI  - Necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is a rare but rapidly progressive and potentially
      fatal disease condition. It is characterized by progressive inflammation and
      extensive necrosis of the subcutaneous tissue and fascia, sparing the underlying
      tissue. It is a poly-bacterial infection and is associated with profound systemic
      toxicity, considerable morbidity and a high mortality rate. The outcome is
      influenced by early recognition and radical surgical debridement. We present a
      report of six cases of NF who presented to our surgical service within the past 5
      years.

PMID- 15267056
TI  - A little known complication in an obstructed right inguinal hernia: five patients
      with afferent limb strangulation.
AB  - Within a period of 6 months five cases of afferent limb strangulation in patients
      with an obstructed right inguinal hernia were seen and treated in our institution
      and are described in this report. Recommendations to avoid pitfalls in the
      management of similar cases are reported.

PMID- 15267057
TI  - Inguinal hernia in Nigeria.

PMID- 15267058
TI  - Practice points in utilizing local volunteers in community health projects.
AB  - Community volunteers are recruited for many health intervention projects. There
      are various motivations for the use of the volunteers and these include: the
      desire to reduce financial costs of projects/programmes; to encourage community
      ownership; ensure long-term sustainability of the health intervention; and to
      empower local communities through training offered the project. Health
      intervention measures working with community volunteers should not be implemented
      without due consideration of issues regarding mobilization and engagement, skills
      and motivation of the volunteers and their effectiveness and efficiency towards
      the attainment of the project goals. This paper discusses some tips that should
      be considered when community volunteers are used in resource-limited situations.

PMID- 15267059
TI  - The prognostic value of admission blood glucose levels in Nigerian patients with
      stroke: a 10-year retrospective analysis.

PMID- 15267060
TI  - Prevalence of Cryptosporidium for foreign workers in Taiwan.

PMID- 15267062
TI  - Knowledge about malaria among primary school teachers in Ndirande, Malawi.

PMID- 15267061
TI  - Higher rate of benign cellular changes of uterine cervix in women with chronic
      mental illness.

PMID- 15267063
TI  - Emerging role of the private sector in HIV/AIDS disease prevention in Pakistan.

PMID- 15267064
TI  - Small volume resuscitation with 7.5% hypertonic saline solution--treatment of
      haemorrhagic shock in the tropics.

PMID- 15267065
TI  - Heterotopic twin delivery of live infants.

PMID- 15267066
TI  - Treatment by practitioners of traditional healing in Malaysia.

PMID- 15267067
TI  - The challenges of counselling in paediatric AIDS.

PMID- 15267068
TI  - Group interactions during space missions.
AB  - INTRODUCTION: Previous anecdotal reports from space and results from space
      simulation studies on Earth have suggested that the group interactions of
      crewmembers during space missions can be problematic in ways that can negatively
      affect crew safety and the accomplishment of mission goals. METHODS: To assess
      the interpersonal environment of space crewmembers, we used a set of standard
      questionnaires that were completed by 5 astronauts, 8 cosmonauts, and 58 American
      and Russian mission control personnel who participated in the Shuttle/Mir
      Program. RESULTS: Although we did not find strong evidence supporting predicted
      decrements in tension and cohesion during the second half of the missions, we did
      find that both crewmembers and mission control personnel displaced unpleasant
      emotions to monitoring personnel outside of their group. We also found
      significant differences between Americans and Russians in terms of measures of
      satisfaction with their interpersonal and work environments. CONCLUSIONS: These
      findings suggest a number of countermeasures to help future space crews deal with
      potential maladaptive group interactions. These countermeasures address issues at
      the time of selection, during prelaunch training, during the mission itself, and
      after the crew returns to Earth.

PMID- 15267069
TI  - The impact of outer space on inner space.
AB  - Thematic content analysis for 11 seminal values was applied to the published
      memoirs of 4 early U.S. astronauts (John Glenn, Gordon Cooper, "Buzz" Aldrin, and
      Michael Collins). Premission values did not show the expected conventional
      pattern; some regularities were observed across the pre-, during-, and postflight
      profiles. Aldrin's post-NASA adjustment problems were possibly related to his
      highly (and uniquely) skewed focus on Achievement to the exclusion of other
      values. Because of the small and unrepresentative sample of both subjects and
      measures, this paper is best considered an illustration of the potential
      usefulness of thematic content analysis in studying the history of human
      spaceflight and the understanding of astronauts' lives.

PMID- 15267070
TI  - Mixed-gender groups: coping strategies and factors of psychological adaptation in
      a polar environment.
AB  - The polar environment is often seen as a good analog for long-term space missions
      in terms of isolation and confinement. This paper focuses on the psychological
      adaptation of both the men and women in mixed-gender groups in the French polar
      station Dumont d'Urville. The first 49 expeditions to this station were composed
      of men only in groups of 25-30. In 2000, two women were included in the first
      mixed-gender wintering group, followed by five women in 2001. This study on
      coping strategies and psychological adaptation was included in an end-of-mission
      debriefing performed by a psychologist. Data were collected using a few
      quantitative tools and a semi-structured interview, and focused on adaptation to
      wintering, coping strategies, and information on interpersonal relationships.
      Including women in a wintering group seems to have had positive effects on the
      general climate of the group by reducing men's rude behavior, but it also seems
      to be an important stressor for both men and women when the females' average age
      is close to the males' because seduction behaviors appear and rivalry,
      frustration, and sexual harassment frequently result. The use of problem-oriented
      strategies helps women to adapt. There are strong arguments indicating that
      living in an isolated and confined environment magnifies the usual difficulties
      that arise in mixed-gender relationships. Difficulties may be magnified in space
      since the group size is smaller and the confinement more extreme. This implies
      the need for rigorous select-in criteria for both men and women, especially for
      relational criteria, and for group training after selection.

PMID- 15267071
TI  - Evaluating teams in extreme environments: from issues to answers.
AB  - The challenge to effectively evaluating teams in extreme environments necessarily
      involves a wide range of physiological, psychological, and psychosocial factors.
      The high reliance on technology, the growing frequency of multinational and
      multicultural teams, and the demand for longer duration missions all further
      compound the complexity of the problem. The primary goal is the insurance of
      human health and well-being with expectations that such priorities will naturally
      lead to improved chances for performance and mission success. This paper provides
      an overview of some of the most salient immediate challenges for selecting,
      training, and supporting teams in extreme environments, gives exemplars of
      research findings concerning these challenges, and discusses the need for future
      research.

PMID- 15267072
TI  - The joint effects of person and situation factors on stress in spaceflight.
AB  - Psychologists can play an important role in spaceflight and exploration. Indeed,
      their input at four specific stages in spaceflight can help to ensure successful
      missions. Psychologists have a role to play in: 1) Selection; 2) Training; 3)
      Real or Simulated Space Missions; and 4) Post-Flight Problems. During selection,
      psychologists can provide guidelines as to the appropriate coping styles for
      reacting to mission-related stressors. During training, psychologists can help
      astronauts to plan for, and cope with, problems (e.g., group conflict). Training
      in social sensitivity, or in specific coping styles (i.e., to be high in task
      oriented coping), would be beneficial so that astronauts are able to deal with
      unforeseen problems. Task-oriented coping is related to control and efficiency,
      and reduces stress and anxiety. Emotion-oriented coping relates to anxiety for
      controllable situations, and task-oriented coping is most efficacious. A primary
      role for psychologists would be the investigation of what problems could arise
      from living with others in a limited space and for long periods of times. As
      such, investigations into group dynamics, physical and psychological stress
      caused by such an environment, and the lack of normal ways to deal with these
      problems should all be considered. It is also clear that the impact of
      spaceflight on an individual does not end with physical re-entry. On the
      contrary, the astronaut will also have to make a psychological post-flight "re
      entry" readjustment to life on Earth. Psychologists have an important role to
      play during all four stages of the space program, especially in regards to person
      by situation interactions. That is, space is a novel environment for human
      beings, and we need to investigate how we can better improve the fit between
      astronauts and space situational stressors. Not only are person by situation
      interactions relevant for each of the four stages discussed above, but each of
      the stages interacts with one another bidirectionally and even
      multidirectionally.

PMID- 15267073
TI  - Group interactions in SFINCSS-99: lessons for improving behavioral support
      programs.
AB  - Human factors can significantly influence successful mission completion of
      prolonged space missions such as ISS expeditions or future Mars missions. This
      paper describes group dynamics and group interactions during SFINCSS-99, a very
      unique international long-term confinement study in a space mission analog
      environment. Many interpersonal or inter-group conflicts occurred, and these
      caused the early retirement of a Japanese subject. This paper cites examples of
      these conflicts, and analyzes their causes with our results. The international
      cooperation to extract lessons learned, which could be used to refine behavioral
      support programs for the ISS or similar international studies, is also
      introduced.

PMID- 15267074
TI  - Interpersonal and group processes in long-term spaceflight crews: perspectives
      from social and organizational psychology.
AB  - The issues of interpersonal and group processes in long-term spacecrews from the
      perspectives of social and organizational psychology are considered here. A
      contrast between the Amundsen vs. Scott expeditions to the South Pole 90 yrs. ago
      highlights the importance of personnel selection and attention to interpersonal
      and group dynamics in expeditions to extreme and dangerous environments, such as
      long-term spaceflights today. Under the rubric of personnel selection, some
      further psychological "select-in" and "select-out" criteria are suggested, among
      them implicit measures of human motivation, intergroup attitudes ("implicit" and
      "explicit" measures of prejudice, social dominance orientation, and right-wing
      authoritarianism), attachment styles, and dispositional hardiness. The
      situational interview and the idea of "selection for teams," drawn from current
      advances in organizational psychology, are recommended for selecting members for
      future spacecrews. Under the rubrics of interpersonal and group processes, the
      social relations model is introduced as a technique for modeling and
      understanding interdependence among spacecrew members and partialling out
      variance in behavioral and perceptual data into actor/perceiver, partner/target,
      and relationship components. Group cohesion as a multidimensional construct is
      introduced, along with a consideration of the groupthink phenomenon and its
      controversial link to cohesion. Group composition issues are raised with examples
      concerning cultural heterogeneity and gender composition. Cultural value
      dimensions, especially power distance and individual-collectivism, should be
      taken into account at both societal and psychological levels in long-term space
      missions. Finally, intergroup processes and language issues in crews are
      addressed. The recategorization induction from the common ingroup identity model
      is recommended as a possible intervention for overcoming and inhibiting
      intergroup biases within spacecrews and between space- and groundcrews.

PMID- 15267075
TI  - Culture and tension during an international space station simulation: results
      from SFINCSS '99.
AB  - BACKGROUND: This paper addresses the impact of cultural heterogeneity on
      interpersonal tension during multinational space missions. METHODS: Data were
      collected during SFINCSS '99, which simulated the living conditions on ISS. Three
      crews (n = 12) were confined in connected hyperbaric chambers. Group 1 was
      confined for 240 d, while Groups 2 and 3 were confined for 110 d. Group 1 was
      composed of four Russian subjects; Group 2 included three Russian subjects and
      one non-Russian subject; and Group 3 included Japanese, Russian, Austrian and
      Canadian subjects. Group 3 included the only female participant. Peer ratings,
      questionnaires and interviews assessed tension within and between crews, critical
      incidents and cultural factors impacting on crew interaction. RESULTS: Compared
      with Group 1, Group 3 evaluated their own group and the Mission Control more
      negatively. A conflict between Group 1 and 3 was reflected in mutual negative
      ratings after 1 mo. This situation resulted in an unplanned closure of the hatch
      between the chambers and in one subject leaving the study prematurely. Group 3
      expressed dissatisfaction with mission support and interventions from outside
      personnel to resolve the interpersonal problems. The entrance of an international
      visiting crew was reported to alleviate tension between Groups 1 and 3. Language
      problems and different attitudes toward gender relations were factors identified
      as having a major impact on the inter-group relationship. CONCLUSIONS: The
      results may demonstrate some of the difficulties faced by crewmembers belonging
      to cultural minorities when operational control is in the hands of one national
      organization, as well as the need for countermeasures designed to address these
      problems.

PMID- 15267076
TI  - Psychology of group relations: cultural and social dimensions.
AB  - Cross-cultural psychology attempts to understand the development and expression
      of human behavior in relation to the cultural contexts in which it occurs. It
      adopts the perspective of "universalism," which assumes that all human beings
      share basic psychological processes, but which are then shaped by cultural
      influences. This perspective allows for the comparison of individuals from
      different cultures (based on the process commonality), but also accepts
      behavioral variability (based on the cultural shaping). In the case of behavior
      that takes place during interactions between individuals coming from two (or
      more) cultures, the task is more complex; we now need to understand at least two
      sets of culture-behavior phenomena, as well as a third set--those that arise at
      the intersection of their relationships. In cross-cultural psychology, we have
      adopted concepts and methods from sociology and political science to inform work
      on "ethnic relations," and from cultural anthropology we have been informed in
      our work on the process and outcomes of "acculturation." In the former domain are
      phenomena such as prejudice and discrimination; in the latter are the strategies
      people use when in daily contact with people from other cultures (such as
      assimilation, integration, separation, and marginalization). These phenomena take
      place in cultural contexts, which need to be understood in terms of the core
      dimensions of cultural difference (such as diversity, equality, and conformity).
      During prolonged and intimate contact between persons of different cultural
      backgrounds, all these psychological concepts and processes, and cultural
      influences need to be taken into account when selecting, training, and monitoring
      individuals during their intercultural interactions.

PMID- 15267077
TI  - Research on intercultural effectiveness and its relevance to multicultural crews
      in space.
AB  - The planning for and managing of missions in space is changing dramatically due
      to, among other things, the involvement of more and more national cultures. In
      light of the need to better understand the influence and management of cultural
      differences among the crewmembers who will live and work in space in the future,
      the aim of this paper is threefold. First, some of the key research findings on
      intercultural effectiveness on Earth are presented and their relevance to the
      functioning of multicultural crews in space is discussed. Second, issues that
      will need to be addressed in order to maximize the effective functioning of
      multicultural teams in space are identified. These include improving the
      procedures for the screening and selection, intercultural training, monitoring
      and support, and debriefing and re-entry of astronauts and their families.
      Finally, the paper concludes with the presentation and discussion of some of the
      key activities that will need to be undertaken to address these issues and,
      thereby, enhance the overall functioning of multicultural teams living and
      working in space.

PMID- 15267078
TI  - Anesthesia during and after exposure to microgravity.
AB  - Human spaceflight has evolved over the past 40 yr in pursuit of larger, more
      complex, and more distant missions. As this evolution continues, inevitably a
      spaceflight crewmember will require medical treatment involving anesthesia,
      either during flight or immediately upon return. If the need occurs during a deep
      space mission, onboard medical staff will need to be capable of surgery and
      anesthesia because evacuation and telemedicine will be impractical. In addition,
      current anesthesia techniques and procedures will have to be adapted to meet the
      special problems and risks that arise in administering anesthesia in space or to
      microgravity-exposed patients. However, very little is known about what those
      adaptations will entail. While there has been some presentient research regarding
      airway management in microgravity suggesting the laryngeal mask airway (LMA) be
      used, only four articles have directly treated the topic of anesthesia care in
      microgravity. Many others, though, have extrapolated applications and
      considerations for microgravity-exposed patients from patients and conditions
      that offer useful adaptation parallels. Researchers have explored parallels to
      orthostatic intolerance adaptations and related neurological, cardiovascular, and
      multifactorial causes. Investigators have also focused on skeletal muscle
      adaptations, especially acetylcholine receptor functional changes and
      redistribution with disuse. These changes may influence the use of depolarizing
      and non-depolarizing neuromuscular blockers in microgravity-exposed patients,
      suggesting they be used with caution. This review surveys, assesses, and compiles
      the existing literature to provide a foundation of consolidated reference for
      future investigations.

PMID- 15267079
TI  - Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading
      in mice.
AB  - INTRODUCTION: Prolonged mechanical unloading induces skeletal muscle weakness, a
      major problem following extended bed rest or spaceflight. Antioxidants are
      reported to partially inhibit the weakness caused by limb immobilization. The
      current study tested allopurinol, a xanthine oxidase inhibitor with antioxidant
      properties, for its capacity to protect the function of unloaded antigravity
      muscles. METHODS: Adult mice conditioned by 12 d of hindlimb suspension, with or
      without allopurinol 50 mg x kg(-1) x d(-1), were compared with freely ambulating
      controls. Animals were anesthetized and soleus muscles were isolated for ex vivo
      analyses. RESULTS: Relative to control muscles, unloading decreased soleus weight
      (-44%; p < 0.05) and cross-sectional area (-38%; p < 0.05), increased cytosolic
      oxidant activity (-46%; p < 0.01), decreased absolute tetanic force (e.g., -64%
      at 250 Hz; p < 0.001 ) and force/area (-35%; p < 0.01), and increased passive
      compliance of the unstimulated muscle (p < 0.05). Allopurinol administration
      blunted the effects of unloading, partially inhibiting losses of absolute force
      (p < 0.05) and force/area (p < 0.05) without affecting muscle atrophy. The drug
      also blunted compliance changes in the passive muscle (p < 0.05). DISCUSSION:
      Allopurinol does not inhibit atrophy of skeletal muscle caused by prolonged
      unloading. However, allopurinol does lessen the contractile dysfunction caused by
      unloading, an action that may have potential benefit for astronauts and bedridden
      individuals.

PMID- 15267080
TI  - Nicotine effects on thermoregulatory responses of men and women during acute cold
      exposure.
AB  - INTRODUCTION: Due to the impact of nicotine (NIC) on the physiological processes
      involved in temperature regulation during cold exposure, it is conceivable that
      NIC may affect the body's thermoregulatory abilities during a cold stress. Thus,
      the purpose of this study was to examine the effects of NIC on thermoregulatory
      responses during acute cold exposure. METHODS: There were six men and six women
      between the ages of 18 and 25 yr who participated in this study. All subjects
      were active, apparently healthy smokers. Each subject performed two cold air
      trials consisting of a 30-min baseline period (BASE) and a 120-min exposure to 10
      degrees C air. One cold air trial was performed following a NIC dosing using a 21
      mg transdermal patch while the other trial was performed after a placebo (PL)
      treatment. RESULTS: During the cold air trials, there were no differences in
      rectal temperature (Tre) or mean skin temperature (Tsk) between the PL and NIC
      treatments in either sex (p > 0.05). However, in men, heat production (M) was 12%
      lower (p < or = 0.05) and tissue insulation was 17% higher (p < or = 0.05) during
      the NIC treatment compared with the PL treatment, while these responses in women
      were unaffected. In both men and women, finger skin vascular conductance
      (SVCfin), expressed as a percentage of the BASE value, was higher during the NIC
      treatment compared with the PL treatment during the cold air trials (p < or =
      0.05). Lastly, throughout the cold air trials, there was no difference in thermal
      sensation between the PL and NIC treatments (p > 0.05). DISCUSSION: In
      conclusion, although NIC administration resulted in sex-specific alterations in M
      and tissue insulation during cold exposure, the response in Tre was unaffected.

PMID- 15267081
TI  - Enhancing circulation to lower limbs during head-down tilt by warming upper body
      and thighs.
AB  - BACKGROUND: Long-duration spaceflight results in deconditioning of the
      cardiovascular system, loss of fluid volume, bone demineralization, and atrophy
      of skeletal muscles, particularly affecting the lower limbs. We hypothesized that
      it is possible to improve blood circulation to the lower extremities in simulated
      microgravity by forcing the blood to deliver heat to the feet through heating
      parts of the upper body and thighs. METHODS: In Study 1, seven men and four women
      were assessed in an environmental chamber with head-down tilt (HDT) at 14
      degrees, wearing a newly developed shortened multi-compartment liquid
      cooling/warming garment (SLCWG) with local tubing networks covering parts of the
      head, torso, thigh, arms, and hands, with fingers, lower leg, and feet exposed.
      Study 2 was the same as Study 1 with a new cohort of four men and two women, and
      the assessment of toe blood perfusion on all subjects. Heat was applied as
      follows: Stage 1--SLCWG inlet water temperature 33 degrees C to stabilize
      comfort; Stage 2--inlet water temperature 8-10 degrees C (in combination with
      HDT) to reach a criterion of 25 degrees C finger temperature (Tfing); and Stage 3
      -inlet water temperature 45 degrees C to restore Tfing to 33 degrees C. RESULTS:
      Improvement of foot circulation by delivering more heat to the upper body and
      thighs was noted; increases in toe temperature (Ttoe) suggest enhanced perfusion.
      From Stage 2 to 3, there were significant increases in Ttoe (p < 0.05), a
      significant decrease in diastolic BP (DBP) (p < 0.05), and a significant change
      across stages in subjective perception of foot comfort (p < 0.001) and foot heat
      (p < 0.06). Further, toe blood perfusion increased significantly from Stage 2 to
      3 (p < 0.05). CONCLUSIONS: Moderate partial heating of the upper body/thighs
      improved blood circulation in the feet in simulated microgravity by delivering
      heat to the lower extremities through restriction of heat exchange with the
      environment in the heated body parts. This technique could serve as a
      supplemental countermeasure for increasing blood circulation to the lower
      extremities.

PMID- 15267082
TI  - Probabilistic model of decompression sickness based on stochastic models of
      bubbling in tissues.
AB  - BACKGROUND: Decompression sickness (DCS) is caused by gas bubbles formed from pre
      existing and new microscopic gas nuclei in blood and tissues. Assuming a random
      pattern of bubbling processes in living tissues, we developed a probabilistic
      model of DCS. We hypothesized that symptoms of DCS in an individual exposed to
      decompression appear when the total volume of bubbles in a unit volume of any
      tissue, w(t), exceeds the critical specific volume of a free gas phase, wcr.
      Therefore, one may consider the expectation of w(t)/wcr as a measure of the
      dynamic risk of gas bubble lesion of a given tissue segment. METHODS: Using the
      standard approach to estimation of various risks and the sum rule of
      probabilities of joint events, we defined the cumulative probability of DCS onset
      by the equation Pcum(t) = 1 - exp[Fcum(t)], where Fcum(t) = sigmaVnQnMnc(t), Qn =
      1/wncr, where Vn is the volume of a tissue n. The function Mnc(t) coincides with
      the function Mn(t), defining a time history of the expectation of wn(t) until it
      achieves its maximum and then becomes a constant. Evaluating Pcum(t) for
      particular altitude decompressions, we identified the additive cumulative risk
      function of development of any DCS symptoms, Fcum-tot(t), with the function
      defining the cumulative risk of any bubble lesion of the "worst" virtual tissue
      (WVT) of Type A. On the other hand, we identified the additive cumulative risk
      function of development of intolerable DCS symptoms, Fcum-int(t), with the
      function defining the cumulative risk of acute bubble lesion of the WVT of Type
      phi. RESULTS: We found parameters of the curves Pcum-tot(t) and Pcum-int(t) that
      fit the known empirical curves for the cumulative probability of DCS onset. For
      men performing mild exercise at 30 kPa after preoxygenation, our estimated
      parameters for curves Pcum-tot(t) indicate that the WVTs of Type A have nitrogen
      washout half-times of 260 and 290 min for preoxygenation times of 75 and 135 min,
      respectively. On the other hand, the parameters of curves Pcum-int(t) show that
      the WVTs of Type phi in men performing mild exercise at 20-40 kPa after
      preoxygenation during 0-6 h are virtual tissues with nitrogen washout half-times
      of 400 to 615 min. CONCLUSION: Our model provides a new approach to predicting
      DCS risk for various decompression profiles. By demonstrating the dependence of
      DCS risk on body tissue parameters, the model explains why resistance to DCS in
      mammals increases with a lower body mass and greater specific blood flow in
      tissues.

PMID- 15267083
TI  - Flight-training effect on the cervical muscle isometric strength of trainee
      pilots.
AB  - External stimulus/loading initiates adaptations within skeletal muscle. It has
      been previously found that the cervical area has the highest loading while
      performing flying maneuvers under +Gz. The first purpose of this study was to
      examine the neck muscle response to the physical environment associated with
      flight training, incorporating limited exposure to +Gz force, in a Pilatus PC-9
      aircraft. The second purpose was to examine the short-term range of movement
      (ROM) response to flight training. Isometric cervical muscle strength and ROM was
      monitored in 9 RAAF pilots completing an 8-mo flight-training course at Pearce
      Airbase in Western Australia, and in 10 controls matched for gender, age, height,
      and weight. Isometric cervical muscle strength and ROM were measured at baseline
      and at 8 mo using the multi-cervical rehabilitation unit (Hanoun Medical,
      Downsview, Ontario, Canada). Results indicated that an increase in pilot neck
      strength was limited to flexion while in a neutral position. No strength changes
      were recorded in any other site in the pilots or for the controls. These findings
      suggest that short-term exposure to the physical environment associated with
      flight training had a limited significant effect on increasing isometric cervical
      muscle strength. No significant changes were observed in pilot ROM, indicating
      that short-term exposure to flight does not effect ROM.

PMID- 15267084
TI  - Stress and coping in a week-long disabled submarine exercise.
AB  - BACKGROUND: Emotional stress could impair cognitive performance and decision
      making in the initial period within a disabled submarine (SUBSUNK). The aim of
      the present study was to explore stress reactions over time in submarine
      crewmembers exposed to a simulated SUBSUNK trial. METHODS: There were 18
      Norwegian sailors who were confined within the front section of a conventional
      diesel-electric submarine for 6 d 18 h complying with emergency SUBSUNK
      procedures. Self-reported measures of habitual coping and personality hardiness
      were completed before the simulation, and measures of emotional stress symptoms
      and quality of life were assessed daily during the exercise and at 2 wk after the
      exercise. RESULTS: A repeated measures analysis of variance showed that emotional
      stress symptoms declined [F (6,14) = 2.76, p < 0.05], while quality of life
      improved over time [F (6,14) = 4.00, p < 0.01] from the first day compared with
      subsequent days of the experiment. Personality hardiness was negatively
      associated with emotional stress (r = -0.52) and lower quality of life (r = 
      0.47), while avoidant coping was positively associated with lower quality of life
      (r = 0.53) in the first 24 h of the SUBSUNK situation (all p < 0.05).
      CONCLUSIONS: These findings suggest that the level of emotional stress was
      highest in the first 24-h period, and that the level of distress was related to
      scores on personality hardiness and personality traits. These data have possible
      implications for selection and healthcare of personnel, and also suggest that
      crews will benefit from external help especially in the first 24 h of emergency
      response techniques.

PMID- 15267085
TI  - From the aerospace medicine residents' teaching file. Pulmonary arteriovenous
      malformations.
AB  - A USAF transport pilot was referred to the Aeromedical Consult Service for a
      cardiology work-up. During his evaluation for an abnormal treadmill, a chest X
      ray showed a probable pulmonary arteriovenous malformation (PAVM). A CT scan of
      his chest and a shunt study confirmed this diagnosis. The aviator was referred
      for treatment and later underwent successful balloon embolization therapy. A
      discussion of PAVM presentation, diagnosis, treatment, and aeromedical aspects
      follows.

PMID- 15267086
TI  - This month in aerospace medicine history--July 2004.

PMID- 15267087
TI  - Canberra vets rally to open animal emergency centre.

PMID- 15267088
TI  - Redundancy test case decision delivers entitlements for employees in small
      business.

PMID- 15267089
TI  - Chip shot.

PMID- 15267090
TI  - What goes up must go up?

PMID- 15267091
TI  - Unpalatable opinions.

PMID- 15267092
TI  - Australian veterinarians who work with horses: an analysis.
AB  - OBJECTIVE: To define and describe the population of Australian veterinarians who
      work with horses. METHOD: Questionnaires were mailed to 866 veterinarians who had
      been identified as working with horses, and 87% were completed and returned. Data
      were entered onto an Excel spreadsheet, and analysed using the SAS System for
      Windows. RESULTS: About 12% of Australia's veterinarians were doing all the
      veterinary work with horses, and about 3% worked exclusively (> 90%) with horses,
      but did more than half (58%) of the horse work. Veterinarians working with horses
      included more males (80%) than the veterinary population as a whole
      (approximately 60%). Males had an average age of 47 years, females 35. Almost all
      (94%) worked in private practice, with 31% being employees, 28% partners and 41%
      sole owners. Females were more likely to be employees than males. Males reported
      working 55 hours/week; females 49. More females (44%) than males (16%) had worked
      less than full-time for more than a year. Males expected to work for another 12
      years in full-time equivalents, and females for 16. One quarter (24%) saw only
      horses, but treated 58% of total horse cases. One-half had < 25% horses, and 29%
      had < 10% of horses in their caseloads. More of the older (54% of those aged >
      60) than younger respondents (27% of those < 40) had grown up on farms with
      animals. One-quarter (24%) decided to become a veterinarian while in primary
      school, and females decided at a younger age than males. Overall, younger
      respondents decided at a younger age than did their older counterparts. A
      veterinarian contributed to the decision for 21% of these veterinarians.
      CONCLUSION: In this survey, Australian veterinarians who work with horses were
      found to be typically male, and advanced in their careers. As these older
      veterinarians retire, there may not be enough veterinarians who are committed to
      and competent with horses to take their places.

PMID- 15267093
TI  - Occupational health risks in veterinary nursing: an exploratory study.
AB  - OBJECTIVES: The aims of this exploratory study were to survey the prevalence of
      certain exposures and health problems among a group of veterinary nurses
      attending the International Veterinary Nurses' Conference in Brisbane, Australia,
      2003 and to identify the main concerns among those veterinary nurses with regard
      to occupational health hazards they may face. METHODS AND MATERIALS: An anonymous
      self-administered questionnaire was distributed among all attendees of the
      International Veterinary Nurses' Conference 2003, Brisbane, Australia (N=147
      respondents among 215 surveyed). RESULTS: The prevalence of exposure to X
      radiation (97%), anaesthetics (96%), disinfectants (96%) and vaccines (85%) was
      high. More than 70% of the nurses were exposed to formaldehyde (76%) and
      pesticides/insecticides (71%). For all exposures except vaccines, about 50% of
      the nurses exposed were worried about negative health consequences. Acute
      injuries were common with 98% of the nurses experiencing dog/cat bites/scratches,
      71% experiencing needle stick injuries and 43% experiencing lacerations. More
      than half of the nurses (52%) suffered from chronic back/neck pain and 39%
      reported having allergy or hay fever. Sixteen cases (11%) of Cat Scratch Fever
      were reported. Job related affective well-being was similar to a large sample of
      workers in comparable level jobs. CONCLUSION: Among attendees of a veterinary
      nurses conference, the proportion of this group of nurses exposed to hazards in
      their work environment was high and acute and chronic injuries were common.
      Considering that nurses account for more than 40% of total employment in the
      veterinary service industry, the results of this study show that the occupational
      health hazards of this professional group require further study.

PMID- 15267094
TI  - Cross reactivity of airborne allergens based on 1000 intradermal test results.
AB  - OBJECTIVE: The purpose of this study was to evaluate concurrent positive
      reactions of related versus nonrelated allergens based on 1000 intradermal tests
      of dogs with atopic dermatitis. PROCEDURE: Pairs of closely related allergens
      (based on botanical relations and results of research in human allergic disease)
      and nonrelated allergens were evaluated. Significance of the difference between
      group means of log odds ratios was estimated using a Bootstrap percentile
      confidence interval. RESULTS: There was a significant difference in the mean log
      odds ratio between related and nonrelated allergen pairs. However, there was also
      a significant difference between most groups consisting of nonrelated allergen
      pairs. CONCLUSION: These results provide conflicting evidence and emphasise the
      need for further studies. Numbers of concurrent reactions of related allergens
      indicate that immunotherapy should be formulated based on testing with single
      allergens to avoid exposure to allergens not involved in the dog's atopic
      disease.

PMID- 15267095
TI  - Cross-sectional study of risk factors for the clinical expression of ovine
      Johne's disease on New South Wales farms.
AB  - OBJECTIVE: To explore the environmental and management risk factors that promote
      the clinical expression of ovine Johne's disease on farms in New South Wales.
      DESIGN: Cross-sectional study. PROCEDURE: A questionnaire about the farm, flock
      and their management was mailed to all farmers known to keep infected sheep in
      the area zoned residual for ovine Johne's disease in New South Wales. The
      resultant data were analysed by multivariate statistical methods, specifically
      examining the factors associated with farmers reporting some mortality due to
      ovine Johne's disease; the reported annual incidence of ovine Johne's disease
      associated mortality; the youngest age at which sheep die from ovine Johne's
      disease; whether scouring was a feature of the disease; and the season of peak
      mortality from ovine Johne's disease. RESULTS: Fine wool Merino sheep were more
      likely to die from ovine Johne's disease than other sheep types. Mortality was
      higher on farms with light sandy soils and those with a high proportion of
      improved pastures containing subterranean clover. Winter shearing was also
      associated with clinical expression. The time that the infection had been present
      on a farm was not strongly associated with mortality. Higher stocking density,
      high rainfall and access to open water, factors that are believed to aid
      transmission, were not found to be influential. CONCLUSION: Clinical expression
      appears to be principally associated with light infertile soils and their
      associated pastures and pasture improvement practices which may lead to
      micronutrient deficiencies or imbalances. Genetic effects are also important and
      are likely to be exacerbated by physiological stressors, such as winter shearing.

PMID- 15267096
TI  - Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested
      cockatoos (Cacatua galerita).
AB  - OBJECTIVE: To determine the pharmacokinetics of carboplatin in sulphur-crested
      cockatoos, so that its use in clinical studies in birds can be considered.
      DESIGN: A pharmacokinetic study of carboplatin, following a single intravenous
      (IV) or intraosseus (IO) infusion over 3 min, was performed in six healthy
      sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were anaesthetised
      and a jugular vein cannulated for blood collection. Carboplatin (5 mg/kg) was
      infused over 3 min by the IV route in four birds via the contralateral jugular
      vein, and by the IO route in two birds via the ulna. Serial blood samples were
      collected for 96 h after initiation of the infusion. Tissue samples from 11
      organs were obtained at necropsy, 96 h after carboplatin administration. Total Pt
      and filterable Pt in plasma and tissue Pt concentrations were assayed by
      inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic
      analysis was performed on the plasma data. RESULTS: The mean +/- SD for the Cmax
      of filterable Pt was 27.3 +/- 4.06 mg/L and in all six birds occurred at the end
      of the 3 min infusion, thenceforth declining exponentially over the next 6 h to
      an average concentration of 0.128 +/- 0.065 mg/L. The terminal half-life (T1/2)
      was 1.0 +/- 0.17 h, the systemic clearance (CI) was 5.50 +/- 1.06 mL/min/kg and
      the volume of distribution (Vss) was 0.378 +/- 0.073 L/kg. The extrapolated area
      under the curve (AUC0-x) was 0.903 +/- 0.127 mg/mL x min; the area extrapolated
      past the last (6 h) data point to infinite time averaged only 1.25% of the total
      AUC0-x. The kidneys had the greatest accumulation of Pt (7.04 +/- 3.006
      microg/g), followed by the liver (3.08 +/- 1.785 microg/g DM). CONCLUSIONS AND
      CLINICAL RELEVANCE: Carboplatin infusion in sulphur-crested cockatoos produced
      mild, transient alimentary tract signs and the Pt plasma concentration was
      similar whether carboplatin was given intravenously or intraosseously. Filterable
      plasma Pt concentrations for carboplatin persisted longer than for cisplatin, due
      mostly to the difference in systemic clearance between these drugs in sulphur
      crested cockatoos. The distribution of tissue Pt after carboplatin administration
      was similar to that reported for cisplatin in sulphur-crested cockatoos. Despite
      anatomical, physiological and biochemical differences among animal species, the
      pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo
      shares some features with the kinetics reported previously in other animals and
      human beings.

PMID- 15267097
TI  - Herpesvirus-like particles in the skin of a saltwater crocodile (Crocodylus
      porosus).

PMID- 15267098
TI  - The role of wild aquatic birds in the epidemiology of avian influenza in
      Australia.

PMID- 15267099
TI  - Taxonomic status and re-description of Plasmodium relictum (Grassi et Feletti,
      1891), Plasmodium maior Raffaele, 1931, and description of P. bigueti n. sp. in
      sparrows.
AB  - The first accurate re-description of Plasmodium relictum (Grassi et Feletti,
      1891) in its type host was provided by Raffaele in 1931, and the name relictum
      should thus refer to this work. In his article, Raffaele noted the presence of an
      associated but distinct species, P. maior. The work of Raffaele has since
      remained overlooked, and the taxon relictum has been applied rather loosely to
      parasites found in numerous birds of diverse geographic origin. Examination of
      Passer domesticus specimens collected in France has confirmed the presence of the
      two species above, and further revealed that two other species can also be found
      in these birds. P. bigueti n. sp. is described here, whereas the other Plasmodium
      sp. was not found in sufficient numbers to allow characterisation.

PMID- 15267100
TI  - Thelazia callipaeda (Spirurida, Thelaziidae) of carnivores and humans:
      morphological study by light and scanning electron microscopy.
AB  - Thelazia nematodes cause ocular infection in several mammals and are transmitted
      by dipteran flies. Thelazia callipaeda Railliet and Henry 1910 (Spirurida,
      Thelaziidae) is common in the Far East, where it causes eyeworm infection in
      carnivores and humans. In the past few years, it has also been reported in dogs,
      cats and foxes in Northern and Southern Italy. Although a great deal of work has
      been carried out in China and other Eastern countries, knowledge of the
      morphology of T. callipaeda is scanty. Eighty-three nematodes collected from the
      eyes of naturally infected dogs from the Basilicata region (southern Italy) were
      examined by light and scanning electron microscopy, and the most important
      features of the nematodes were described. The morphological characteristics
      useful for the identification of T. callipaeda are discussed.

PMID- 15267101
TI  - Synergistic and antagonistic interactions between haemozoin and bacterial
      endotoxin on human and mouse macrophages.
AB  - Haemozoin (malaria pigment) is a birefringent crystalline material made of Fe
      (III) Protoporphyrin IX dimers that derives from the degradation of haemoglobin
      by intraerythrocytic Plasmodia. At schizont rupture, it accumulates indigested
      inside phagocytic cells altering their immunological properties. Both pro
      inflammatory and immunosuppressive activities have been associated with pigment
      fed monocyte-macrophages or dendritic cells. These conflicting results were
      attributed to the source of macrophages or the different preparations of pigment.
      However, the interactions of malaria pigment with other phagocytes stimuli, such
      as bacterial endotoxin (LPS) or interferon-gamma have not been fully analysed,
      yet. The purpose of this study was to compare the immunological properties of
      native haemozoin (HZ), freshly extracted from Plasmodium falciparum cultures,
      versus beta-haematin (BH), the synthetic crystals identical to native haemozoin,
      and to evaluate the relationship between haemozoin and endotoxin on the immune
      response of different macrophages populations. The results indicate that the iron
      porphyrin moiety of both native and synthetic pigment can exert either a
      synergistic or antagonistic effect with LPS that is related to the length and
      sequence of treatment, the source of macrophages and is associated with the
      generation of oxidative stress. These data rise the question of whether and how
      in vivo concomitant gram(-) bacteremia may affect the pathogenesis and/or the
      immune response of malaria infections and vice versa.

PMID- 15267102
TI  - Clinical Toxoplasma gondii, Hammondia heydorni, and Sarcocystis spp. infections
      in dogs.
AB  - Concurrent infections with coccidians Toxoplasma gondii, Sarcocystis spp., and a
      Hammondia heydorni-like parasite were identified in tissues of three littermate
      pups on a Kelpie dog breeding farm in Australia. In total, 20 pups in four
      litters had died following vaccination with an attenuated distemper virus
      vaccine. Toxoplasma gondii tachyzoites were identified immunohistochemically in
      tissues of two dogs. Sarcocystis sp. sporocysts were seen in the intestinal
      lamina propria of two dogs. Asexual and sexual stages of H. heydorni-like
      parasite were found in enterocytes of the small intestine of two dogs.
      Ultrastructural development of schizonts and gamonts of this parasite is
      described. None of the protozoa in these dogs reacted with antibodies to Neospora
      caninum. Feeding of uncooked tissue of sheep was considered to be the likely
      source of infection for these coccidians in dogs.

PMID- 15267103
TI  - New records of alien monogeneans from Lepomis gibbosus and Silurus glanis in
      Italy.
AB  - The first geographical records of five alien monogeneans for Italy is reported.
      Four species have been detected from Lepomis gibbosus (Linnaeus, 1758):
      Actinocleidus recurvatus Mizelle et Donahue, 1944, Actinocleidus oculatus
      (Mueller, 1934), Urocleidus similis (Mueller, 1936) and Urocleidus dispar
      (Mueller, 1936); one species from Silurus glanis Linnaeus, 1758: Thaparocleidus
      vistulensis (Siwak, 1932) n. comb.

PMID- 15267104
TI  - Effects of thiabendazole in Mansonella perstans filariasis.
AB  - Mansonella perstans is a human filarial parasite distributed across the center of
      Africa and equatorial America. Although M. perstans infection is asymptomatic in
      most individuals, a variety of symptoms have been described, including
      angioedema, pruritus, fever, ocular involvement, and serous cavities pain.
      Eosinophilia is found in many cases. Treatment with diethyl-carbamazine or
      mebendazole is often ineffective. We present a study on the effects of
      thiabendazole in the treatment of symptomatic M. perstans filariasis. Twenty-five
      patients were treated with thiabendazole at a single dose of 50 mg/kg for
      children and 3 g for adults. Sixteen out of 25 subjects repeated a second dose a
      week later. Parasite density, eosinophilia, and symptoms were significantly
      reduced after both one and two-step therapy in most patients. This study shows
      that thiabendazole may be effective in M. perstans infection. More studies are
      needed to determine a more effective dosage, or a putative combination treatment.

PMID- 15267105
TI  - [Editorial note: Italian antimalarial legislation, with particular reference to
      the State's quinine laws].

PMID- 15267106
TI  - Medicine without doctors.

PMID- 15267107
TI  - Characterization of a mitochondrion-like organelle in Cryptosporidium parvum.
AB  - Cryptosporidium parvum is a protozoan parasite that causes widespread diarrhoeal
      disease in humans and other animals and is responsible for large waterborne
      outbreaks of cryptosporidiosis. Unlike many organisms belonging to the phylum
      Apicomplexa, such as Plasmodium spp. and Toxoplasma gondii, there is no
      clinically proven drug treatment against this parasite. Aspects of the basic
      biology of C. parvum remain poorly understood, including a detailed knowledge of
      key metabolic pathways, its genome organization and organellar complement.
      Previous studies have proposed that C. parvum lacks a relic plastid organelle, or
      'apicoplast', but that it may possess a mitochondrion. Here we characterize a
      mitochondrion-like organelle in C. parvum by (i) ultrastructural and
      morphological description (ii) localization of heterologous mitochondrial
      chaperonin antibody probes (iii) phylogenetic analysis of genes encoding
      mitochondrial transport proteins (iv) identification and analysis of
      mitochondrion-associated gene sequences. Our descriptive morphological analysis
      was performed by energy-filtering transmission electron microscopy (EFTEM) of C.
      hominis and C. parvum. The 'mitochondrion-like' organelle was characterized by
      labelling the structure with a heterologous mitochondrial chaperonin probe
      (hsp60) both in immunoelectron microscopy (IMEM) and immunofluorescence (IMF).
      Phylogenetic analysis of the mitochondrial import system and housekeeping
      components (hsp60 and hsp70-dnaK) suggested that the C. parvum mitochondrion-like
      organelle is likely to have descended from a common ancestral apicomplexan
      mitochondrion. We also identified a partial cDNA sequence coding for an
      alternative oxidase (AOX) gene, a component of the electron transport chain which
      can act as an alternative to the terminal mitochondrial respiratory complexes III
      and IV, which has not yet been reported in any other member of this phylum.
      Degenerate primers developed to identify selected mitochondrial genes failed to
      identify either cytochrome oxidase subunit I, or cytochrome b. Taken together,
      our data aim to provide new insights into the characterization of this
      Cryptosporidium organelle and a logical framework for future functional
      investigation.

PMID- 15267108
TI  - Cysteine proteinase activity is required for survival of the parasite in
      experimental acute amoebic liver abscesses in hamsters.
AB  - Axenic trophozoites of Entamoeba histolytica strain HM1-IMSS grown in vitro in
      the presence of E-64, a potent irreversible inhibitor of cysteine proteinases,
      preserved their viability, their rate of replication, their resistance to
      complement, their haemolytic capacity and their ability to destroy target cells,
      despite complete inhibition of total cysteine proteinase activity. On the other
      hand, their erythrophagocytic capacity and their ability to decrease TER of MDCK
      cells was partially decreased. The same trophozoites injected into the portal
      vein of hamsters receiving a maintaining dose of E-64 failed to cause tissue
      damage and were rapidly eliminated. Our results suggest that amoebic cysteine
      proteinase activity is not required for amoebic functions in in vitro conditions,
      but that it becomes necessary for survival of trophozoites in in vivo conditions,
      whatever other role (if any) it may play in the parasite's virulence.

PMID- 15267109
TI  - The persistence of component Theileria parva stocks in cattle immunized with the
      'Muguga cocktail' live vaccine against East Coast fever in Uganda.
AB  - The 'Muguga cocktail' live vaccine comprises three Theileria parva stocks
      (Muguga, Kiambu 5 and the buffalo-derived Serengeti-transformed) and has been
      used extensively in Eastern, Central and Southern Africa with an infection and
      treatment protocol to protect cattle against East Coast fever. We report the
      characterization of the three component vaccine stocks using a panel of
      polymorphic micro-satellite and mini-satellite markers and the development of a
      stock-derived PCR method that distinguishes two of the vaccine stocks. These
      markers, with the use of a recently developed Reverse Line Blot assay, have
      enabled us to address four important questions in relation to vaccination. First,
      how closely related are the vaccine stocks, secondly do all three stocks persist
      post-vaccination and induce a carrier state, thirdly is there evidence for the
      transmission of the vaccine stocks and fourthly does vaccination prevent
      infection with local genotypes? The results show that Muguga and Serengeti
      transformed stocks are highly related but very distinct from Kiambu 5 that
      persists in vaccinated cattle establishing a carrier state. No evidence was
      obtained for the transmission of vaccine stocks to co-grazed animals, although
      these animals were infected with up to 8 different T. parva genotypes showing
      there was a significant level of tick challenge. Some of the vaccinated animals
      become infected with a subset of local genotypes providing evidence for limited
      vaccine 'breakthrough'.

PMID- 15267110
TI  - Vector survival and parasite infection: the effect of Wuchereria bancrofti on its
      vector Culex quinquefasciatus.
AB  - This paper investigates a cohort of 2187 laboratory reared Culex quinquefasciatus
      fed on 69 human volunteers, including 59 persons with different levels of
      Wuchereria bancrofti microfilariae and 10 without microfilaria. Mosquitoes were
      followed until death. Mosquito survival was analysed in relation to the level of
      microfilaria in the human and larval count in the dead mosquito. Vector mortality
      during the extrinsic incubation period (12 days post-engorgement) was
      significantly higher in mosquitoes fed on microfilaraemic volunteers (50%) than
      in those fed on amicrofilaraemics (29%). Both the percentage infected and the
      geometric mean parasite density was significantly higher among mosquitoes which
      died before 13 days (45% infected and 10 larvae per infected mosquito) than those
      surviving beyond 13 days (39% and 2.2), suggesting a parasite loss of more than
      80% during the extrinsic incubation period. A large proportion (62%) of the
      mosquitoes that died during the early of phase of parasite development were
      infected (36% in low, 26% in medium and 90% in high human Mf-density). Survival
      analysis showed that the parasite load in mosquitoes and the human Mf-density for
      a given parasite load are independent risk factors of vector survival. Overall,
      the hazard of dying was found to be 11-15 times higher among mosquitoes fed on
      microfilaraemic volunteers than those fed on amicrofilaraemics. The hazard
      doubles for every increase of about 60-70 parasites in the vector. As a
      consequence of the parasite-induced reduction in vector survival, the
      transmission success of the parasite is reduced. The implication of the results
      on control/elimination of lymphatic filariasis using mass-drug administration is
      discussed.

PMID- 15267111
TI  - ATP diphosphohydrolase from Schistosoma mansoni egg: characterization and
      immunocytochemical localization of a new antigen.
AB  - The fact that the Schistosoma mansoni egg has two ATP diphosphohydrolase (EC
      3.6.1.5) isoforms with different net charges and an identical molecular weight of
      63,000, identified by non-denaturing polyacrylamide gel electrophoresis and
      immunological cross-reactivity with potato apyrase antibodies, is shown. In
      soluble egg antigen (SEA), only the isoform with the lower net negative charge
      was detected and seemed to be the predominant species in this preparation. By
      confocal fluorescence microscopy, using anti-potato apyrase antibodies, the S.
      mansoni egg ATP diphosphohydrolase was detected on the external surface of
      miracidium and in von Lichtenberg's envelope. Intense fluorescence was also seen
      in the outer side of the egg-shell, entrapped by the surface microspines,
      suggesting that a soluble isoform is secreted. ATP diphosphohydrolase
      antigenicity was tested using the vegetable protein as antigen. The purified
      potato apyrase was recognized in Western blots by antibodies present in sera from
      experimentally S. mansoni-infected mice. In addition, high levels of IgG anti-ATP
      diphosphohydrolase antibodies were detected by ELISA in the same sera. This work
      represents the first demonstration of antigenic properties of S. mansoni ATP
      diphosphohydrolase and immunological cross-reactivity between potato apyrase and
      sera from infected individuals.

PMID- 15267112
TI  - Size versus health as a cue for host choice: a test of the tasty chick
      hypothesis.
AB  - Knowledge about how parasites choose their hosts is scarce and incomplete. Recent
      work has primarily focused on host health (i.e. immunocompetence) whereas
      ecological factors have been largely neglected. Here we investigate whether the
      immunocompetence, the nutritional condition or body size of nestling European bee
      eaters Merops apiaster are used as parameters for habitat choice of the
      haematophagous fly Carnus hemapterus. We found that (i) flies consistently and
      nonrandomly preferred larger nestlings, even after controlling for differences in
      habitat availability (host surface), (ii) in the presence of similar-sized hosts,
      parasites' choice for an individual was less likely than if hosts differed in
      size, (iii) the more the hosts differed in size, the more the parasites
      aggregated on the larger nestling and (iv) parasites changed their preference
      according to size criteria regardless of the identity of the larger host. Neither
      immunocompetence nor host body condition could account for parasites' preference.
      Our results do not support the prediction of the Tasty Chick Hypothesis, namely
      that the poor immunocompetence ability of junior chicks makes them more
      attractive to parasites. We conclude that basic ecological factors (e.g. body
      size) can be essential for parasites when choosing a host.

PMID- 15267113
TI  - In vitro effects of three woody plant and sainfoin extracts on 3rd-stage larvae
      and adult worms of three gastrointestinal nematodes.
AB  - Most studies on the effects of tanniferous plants on nematodes have examined
      forages but have neglected the woody plants. Therefore, in vitro effects of
      extracts from 3 woody plants (Rubus fructicosus, Quercus robur, Corylus avellana)
      have been tested on trichostrongyles and compared to sainfoin, a legume forage.
      Because some in vivo results indicated that the effects of tannins differed
      depending on the parasitic species and/or stages, the effects were measured on
      3rd-stage larvae (L3) and adult worms of Teladorsagia circumcincta, Haemonchlus
      contortus and Trichostrongylus colubriformis. The effects of plant extracts
      varied according to the plant sources, the parasite species and stages. For the
      woody plants, significant inhibitory effects were obtained on both stages of
      abomasal species. Results for T. colubriformis were more variable. Effects of
      sainfoin extracts were significant on T. colubriformis and H. contortus L3, and
      on abomasal adult worms. In order to assess the implications of tannins,
      polyethylene glycol (PEG), an inhibitor of tannins, was added to hazel tree, oak
      and sainfoin extracts. Without PEG, significant inhibitory effects on L3 and
      adult worms were confirmed. After addition of PEG, the larval migration and
      motility of adult worms were restored in most cases. These results confirm
      variations in effects depending on factors related to plants or parasites and
      suggest that tannins are partly responsible for the effects.

PMID- 15267114
TI  - Purification and characterization of two iron superoxide dismutases of Phytomonas
      sp. isolated from Euphorbia characias (plant trypanosomatids).
AB  - Two superoxide dismutases (SODI and SODII) have been purified by differential
      centrifugation, fractionation with ammonium sulphate followed by chromatographic
      separation (ionic exchange and affinity), from a plant trypanosomatid isolated
      from Euphorbia characias, and then characterized for several biochemical
      properties. Both enzymes were insensitive to cyanide but sensitive to hydrogen
      peroxide, properties characteristic of iron-containing superoxide dismutase. SODI
      had a molecular mass of approximately 66 kDa, whereas the molecular mass of SODII
      was approximately 22 kDa, both enzymes showing single bands. The isoelectric
      points of SODI and SODII were 6.8 and 3.6, respectively. The enzymatic stability
      persisted at least for 6 months when the sample was lyophilized and preserved at 
      80 degrees C. Digitonin titration and subcellular fractionation showed that both
      enzymes were in the cytoplasmic fraction, although part of SODII isoenzyme was
      also associated with glycosomes. We assayed these activities (SOD) in 18
      trypanosomatid isolates on isoelectric focusing gels, and have demonstrated that
      the SOD is a biochemical marker sufficient to identify a trypanosomatid isolated
      from a plant as belonging to the genus Phytomonas and to distinguish between a
      true Phytomonas and other trypanosomatids that are capable of causing transient
      infections in plants.

PMID- 15267115
TI  - Patterns of cercarial production from Diplostomum spathaceum: terminal investment
      or bet hedging?
AB  - In the production of the infective cercariae of trematodes, the terminal
      investment hypothesis of life-history theory predicts that the rate of host
      exploitation and cercarial production should increase during the period of
      cercarial shedding since the reproductive value of the parasite decreases during
      this period. In contrast, a bet hedging hypothesis that focuses on the success of
      transmission when host contact rate is variable predicts that cercarial
      production should decrease in an attempt to keep the host alive for longer and
      thus would increase the probability of successful transmission. We examined these
      two hypotheses under laboratory conditions and recorded the production of
      Diplostomum spathaceum cercariae from naturally infected snail hosts, Lymnaea
      stagnalis. The average number of cercariae produced per day decreased as the
      snail host approached death counter to the terminal investment hypothesis. The
      finding supports the prediction of the bet hedging hypothesis and implies that
      the pattern of cercarial production may be explained by reduced virulence of the
      parasite within the snails to ensure extended total production time of cercariae.
      Nevertheless, survival of infected snails was still lower than uninfected snails
      suggesting that ultimately the infection still increased snail mortality rate.
      Cercarial production varied between days but was not cyclic, probably because of
      the physiology of the sporocysts within snails. Fewer cercariae were released at
      night, which may increase transmission efficiency to diurnally-active fish hosts.
      The mechanisms associated with daily cercarial production are discussed.

PMID- 15267116
TI  - An experimental field approach to parasitism and immune defence in voles.
AB  - The fox tapeworm Echinococcus multilocularis is typically perpetuated in a cycle
      with red foxes as definitive hosts and various rodent species as intermediate
      hosts. In this study, foxes were baited with a highly efficient drug against
      cestodes (praziquantel) in 5 blocks of 1 km2. Voles, Arvicola terrestris, the
      most abundant intermediate host species, were trapped in the 5 baited blocks and
      in 5 non-baited control blocks. Baiting the foxes reduced the prevalence of E.
      multilocularis in fox faecal samples in the baited blocks, but voles trapped in
      the two blocks did not differ in their infection rates. However, voles from the
      baited blocks had significantly smaller spleen masses and were more likely to be
      infested with mites than those from the control blocks, possibly reflecting
      different immunological activities. Our study suggests that the environmental
      contamination with E. multilocularis eggs, and perhaps those of other tapeworms,
      influences the immune system of the intermediate host species A. terrestris in
      the wild.

PMID- 15267117
TI  - Spatial variation in helminth community structure in the red-legged partridge
      (Alectoris rufa L.): effects of definitive host density.
AB  - Parasite community ecology has recently focused on understanding the forces
      structuring these communities. There are few surveys, however, designed to study
      the spatial repeatability and predictability of parasite communities at the local
      scale in one host. The purpose of our study was to address the relationship
      between infracommunity and component community richness, and to describe spatial
      variations on the local scale, of helminth parasite communities in an avian host,
      the red-legged partridge (Alectoris rufta). We sampled 235 wild partridges from 8
      separate localities, with different partridge population densities, in the Ciudad
      Real and Toledo provinces of central Spain, and we determined their overall and
      intestinal helminth species. We found that habitat variables (mean temperature
      and land use) were not significantly associated with any component community. The
      partridge population abundance index was directly correlated with the prevalence
      and mean intensity of infection but not with component community species
      richness. There was a curvilinear relationship between infracommunity and
      component community species richness, as well as negative interspecific
      associations, for the helminth species assemblage parasitizing the intestine. A
      nestedness/anti-nestedness pattern, considered as part of a continuum, was
      associated with prevalence, mean intensity and partridge population abundance
      index, but not with component community richness. Increases in the partridge
      population abundance index and the prevalence and mean intensity of infection
      were associated with increases in helminth community nestedness. Although
      negative interactions between helminth species could not be ruled out as forces
      structuring helminth communities, our results suggest that parasite community
      structure in the red-legged partridge was primarily determined by the extrinsic
      influence of parasite habitat heterogeneity and its amplification of the
      differing probabilities of colonization of parasite species.

PMID- 15267118
TI  - Copro-antigen capture ELISA for the detection of Teladorsagia (Ostertagia)
      circumcincta in sheep: improvement of specificity by heat treatment.
AB  - A copro-antigen capture ELISA for the detection of Teladorsagia circumcincta
      infection in sheep was developed and evaluated. Experiments with faeces from worm
      free sheep, that had been spiked with known concentrations of excretory-secretory
      (E-S) antigen indicated that a positive signal was generated with 180 ng of E
      S/ml. A nested design, based on 8 infected and 8 worm-free sheep, was employed to
      assess the stages during sample preparation contributing to variation in signal
      from the assay. This showed that 87% of the variance in the optical density
      readings (ODs) was directly explained by infection status. Variation between
      individual sheep within infection groups, and between samples at various stages
      in the assay, collectively accounted for the remaining variance. Initial
      evaluation of specificity using faeces from animals carrying a range of
      monospecific infections indicated cross-reactivity with Haemonchus contortus and
      Nematodirus spathiger. However, by treating the supernatant from faeces for 20
      min at 100 degrees C, the cross-reactive signal was eliminated whilst the
      specific signal was largely preserved. Heat treatment of faeces from 12 non
      infected sheep, 12 sheep with T. circumcincta and 6 with H. contortus resulted in
      sensitivity being increased from 66.7 to 85.7%, and specificity from 62.5 to
      87.5%. OD values showed a significant positive relationship with adult worm
      burdens, although at low infection intensities there was some overlap between
      infected and worm-free animals. We discuss the application of CC-ELISAs in
      facilitating selective chemotherapy of sheep, as a means of avoiding the
      development of anthelmintic resistance in pastoral regions where sheep are farmed
      on a large scale.

PMID- 15267119
TI  - Perception of cultural correlates of medicine: a comparison between medical and
      non-medical students--the authoritarian health.
AB  - Aim of the study was to ascertain if a common cultural feeling of young people
      toward health, disease, physician's role and doctor-patient relationship, is
      present, and if under- and post-graduate students concepts and opinions modify
      during their stay in a School of Medicine. The study (1999-2001) was performed by
      anonymous questionnaires with 75 students (m = 28; f = 47) of the State School of
      Medicine, tested at the 3rd year, and with 73 students (m = 29; f = 44) tested at
      the 5th year of course; moreover with 71 (m = 30, f = 41) postgraduate residents
      at the 3rd year of specialty (Internal Medicine, Cardiology and Surgery). A group
      of 76 (m = 33; f = 43) students of the last year of a high school was also tested
      as reference group. RESULTS: Interference of medical under- and post-graduate
      school curricula on thoughts of youngsters toward health, disease, physician's
      role and doctor-patient relationship appears quite limited. Dissimilar way of
      thinking of medical vs. non-medical students was confined to some aspects
      concerning patient's possibility of healing, physician's role, behavior and
      function in chronic diseases. In the whole, our results suggest a trend, growing
      with the age of students, toward a more authoritarian and less "participative"
      approach with the patient: less confident relationship and more conflictual and
      antagonistic behaviors are widely considered and accepted. A general perspective
      with the construct of an authoritarian concept of health is superimposed as a net
      of rules and conditions on feelings' background of youngsters: postgraduate
      students regard themselves (and are perceived by younger students) as the
      guardians of an "healthy" system founded on scientific, economical and
      sociological grounds, as a work pointing to effectiveness, more than as a science
      with the target of efficacy. CONCLUSION: Impact of curricular studies of Medicine
      on youngsters is complex, but seems to modify only some and limited aspects of
      previously acquired thoughts and feelings on health and disease.

PMID- 15267120
TI  - Fluconazole resistance in Candida albicans: a review of mechanisms.
AB  - Antifungal agents have greatly contributed to the improvement of public health.
      Nevertheless, antifungal resistant pathogens have increased during the past
      decade, becoming a serious concern. Candida albicans has been the most
      extensively studied pathogen in antifungal resistance because of their morbidity
      and mortality associated with infections in immunocompromised patients. This
      review describes the antifungal mechanims of the azole fluconazole widely used
      for the prophylaxis and treatment of candidal infections. The specific molecular
      pathways occurring in fluconazole-resistance of C. albicans and some issues about
      new antifungal agents are also discussed.

PMID- 15267121
TI  - A randomised trial comparing submucosal haemorrhoidectomy with radiofrequency
      bistoury vs. diathermic haemorrhoidectomy.
AB  - BACKGROUND: Haemorrhoid disease has become more and more frequent during the past
      years among western populations. Great attention has been paid in development of
      surgical procedures, in order to reduce post-operative pain (the main adverse
      effect of surgical treatment for haemorrhoids) and shorten execution time and
      hospital stay. This randomised clinical study compares the results obtained using
      submucosal haemorrhoidectomy with radiofrequency vs. diathermic
      haemorrhoidectomy. METHODS: Thirty-one patients were randomised to undergo
      submucosal haemorrhoidectomy with radiofrequency bistoury (16 patients, Group A)
      or diathermic haemorrhoidectomy (15 patients, Group B). The operating time,
      amount of pain and postoperative analgesic requirement, intra and post-operative
      complications and patient satisfaction were documented. RESULTS: The mean values
      for operative time have been 35.8 min for group A and 23.2 min for group B.
      According to pain score, patients' mean values for first day postoperative pain
      were 3.8 (A) and 5.8 (B). Pain at first evacuation 4.7 (A) and 6.5 (B). Pain at
      7th postoperative day was 2.3 (A) and 3.7 (B). Patient's postoperative
      satisfaction rate was 6.0 (A) vs. 5.2 (B) at 3rd day and 6.7 (A) and 5.7 (B) at 6
      months. CONCLUSIONS: In spite of relatively difficult execution and longer
      operating times, submucosal haemorrhoidectomy with radiofrequency bistoury
      appears to be the most precise and accurate treatment for IV degree haemorrhoids.
      Performing submucosal haemorrhoidectomy with radiofrequency bistoury allows us to
      reduce postoperative pain, bleeding and shorten hospital stay.

PMID- 15267122
TI  - Lactobacilli for prevention of urogenital infections: a review.
AB  - Urogenital infections are a worldwide shared problem that represent the most
      common reason for a woman to decide to visit to gynaecologist or urologist. The
      origin of the uropathogens in uncomplicated urinary tract infection and bacterial
      vaginosis is the fecal flora. Key element of pathogenesis namely the ability of
      the pathogens to survive exposure to the microflora that exists on the external
      urogenitalia, in which lactobacilli predominate. Some health food appear to
      contain > or = 1 common Lactobacillus strain; L. rhamnosus GR-1 was found to be
      the best of a group of 34 Lactobacillus strains isolated from dairy, poultry,
      health food. Recently has been reported the first clinical evidence that
      probiotic lactobacilli can be delivered to the vagina following oral intake.
      These L. strains possess the ability to adhere to and colonize tissues and the
      capacity to inhibit the pathogenesis of disease-causing organisms that make them
      effective probiotic agents. In particularly, two strains, Lactobacillus GG and
      Lactobacillus rhamnosus GR-1 appear to be effective at colonizing and protecting
      the intestine and urogenital tract, respectively, against microbial infection.
      Treating and preventing urogenital infection by instillating probiotic organisms
      has great appeal to patients and caregivers. The ability to administer orally L.
      rhamnosus GR-1 and L. fermentum RC-14, which colonize the intestine and vagina,
      provides a major step in the right direction for patients as it potentially
      allows for the self administration of therapy.

PMID- 15267124
TI  - Level of processing and age affect involuntary conceptual priming of weak but not
      strong associates.
AB  - Memory for weak and strong semantic associates was compared in intentional
      associate-cued-recall and incidental free-association tests. This design yielded
      four conditions (weak/intentional, strong/intentional, weak/incidental, and
      strong/ incidental) on which younger and older adults were compared. Level of
      processing (LOP) and age effects occurred for the weak/intentional,
      strong/intentional, and weak/incidental conditions, but not for the
      strong/incidental condition. Because participants could not distinguish weak from
      strong associates during the memory tests, these results suggest that free
      association priming was involuntary and was not contaminated by voluntary
      retrieval strategies. Instead, they suggest that encoding deficits related to
      shallower LOP and older age reduce involuntary free-association priming mainly
      for associates without cohesive preexperimental representations.

PMID- 15267125
TI  - Is the implicit association test immune to faking?
AB  - One of the main advantages of measures of automatic cognition is supposed to be
      that they are less susceptible to faking than explicit tests. It is an empirical
      question, however, to what degree these measures can be faked, and the response
      might well differ for different measures. We tested whether the Implicit
      Association Test (IAT, Greenwald, McGhee, & Schwartz, 1998) cannot be faked as
      easily as explicit measures of the same constructs. We chose the Big-Five
      dimensions conscientiousness and extraversion as the constructs of interest. The
      results show, indeed, that the IAT is much less susceptible to faking than
      questionnaire measures are, even if no selective faking of single dimensions of
      the questionnaire occurred. However, given limited experience, scores on the IAT,
      too, are susceptible to faking.

PMID- 15267123
TI  - Antiresorption therapy and reduction in fracture susceptibility in the
      osteoporotic elderly patient: open study.
AB  - The identification of risk factors for osteoporosis has been an essential step
      towards the understanding of the onset of the disease as well as of the
      osteoporosis-related fractures due to bone fragility. The present study has been
      aimed at assessing whether a correlation may exist between the increment in bone
      mass, consequent to an antiresorption therapy, and the reduction in the incidence
      of fractures. Moreover, the possibility that such a reduction might result from
      the action of other factors, such as the changes in bone microstructure, has been
      investigated. A total of 2,000 osteoporotic women (mean age: 68 +/- 9 years) were
      enrolled in the study and divided at random into 4 treatment groups. Each group
      received one of the following treatments: Alendronate 10 mg/daily (1,000
      patients), Clodronate 100 mg/weekly i.m. (800 patients), Risedronate 5 mg/dailt
      (100 patients), and Raloxifene 60 mg/daily (100 patients). Clinical evaluation
      was based on bone mineral density (BMD) assay on lumbar vertebrae (L1-L4) by
      means of a DEXA (Lunar DPX) mineralometer, as well as on the incidence of
      fractures following both 12- and 24-month treatment periods. The results showed
      an overlapping pattern in patients treated with Alendronate or Risedronate,
      namely a significant increment in BMD after a 24-month treatment period, whereas
      such an increment in BMD was less evident in patients receiving either Clodronate
      or Risedronate after a 24-month treatment period. In addition, a total of 18
      osteoporosis-related fractures were observed during the entire study period; 10
      out of 18 fractures occurred in the Alendronate treated group, whereas the
      remaining 8 fractures were observed in the Clodronate treated group. Fourteen
      fractures were detected in patients over 80-year old, whereas the remaining 4
      occurred in patients aged from 70 to 79 years and appeared to be independent of
      both the T-score assigned and the BMD increment obtained as a result of the
      therapy. Such findings suggest that the plain monitoring of BMD appears not to be
      adequate to anticipate clearly the danger of the probable onset of additional
      fractures, while the higher incidence of fractures in patients over 80-year old
      evidences that "old age" has to be considered the most serious risk factor for
      osteoporosis, since it is also the real responsible factor for changes taking
      place in bone microstructure.

PMID- 15267126
TI  - The direction of affective priming as a function of trait anxiety when naming
      target words with regular and irregular pronunciation.
AB  - Results from an affective priming experiment confirm the previously reported
      influence of trait anxiety on the direction of affective priming in the naming
      task (Maier, Berner, & Pekrun, 2003): On trials in which extremely valenced
      primes appeared, positive affective priming reversed into negative affective
      priming with increasing levels of trait anxiety. Using valenced target words with
      irregular pronunciation did not have the expected effect of increasing the extent
      to which semantic processes play a role in naming, as affective priming effects
      were not stronger for irregular targets than for regular targets. This suggests
      the predominant operation of a whole-word nonsemantic pathway in reading aloud in
      German. Data from neutral priming trials hint at the possibility that negative
      affective priming in participants high in trait anxiety is due to inhibition of
      congruent targets.

PMID- 15267127
TI  - Lost in thought: cognitive load and the processing of addressees' feedback in
      verbal communication.
AB  - Two experiments tested if cognitive load interferes with perspective-taking in
      verbal communication even if feedback from the addressee is available.
      Participants gave instructions on the assembly of a machine model. In Experiment
      1, cognitive load was demonstrated to be a function of the complexity of assembly
      steps. In Experiment 2, position of feedback (during simple vs. during complex
      steps) and type of feedback (question vs. ambiguous interjection) were
      manipulated. With simple steps, speakers' responses were a function of feedback
      type. Speakers responded differently to questions than to interjections. With
      complex steps, however, responses were a function of cognitive load. Regardless
      of the type of feedback, most speakers simply repeated their previous utterances.

PMID- 15267128
TI  - A multinomial model to assess central characteristics of mental operators.
AB  - Knowledge about potential operators, about the preconditions of their
      applicability, and about their effects is essential to interact effectively with
      the physical world. Four classes of representational units of this knowledge can
      be distinguished: I) rules, II) structures, III) instances, and IV) episodes. Two
      important characteristics of these units are the abstractness of content and the
      directionality of access. A multinomial model is presented that enables the
      measurement of these characteristics. Three experiments were conducted to
      validate the parameters of the model. The multinomial model could be fitted very
      well to the empirical data of each experiment. Moreover, the parameter estimates
      showed the expected effects. The model allows the investigation of the influence
      of important variables (for example, knowledge domain, type of instruction, or
      amount of practice) on characteristics of mental operators without a strong
      commitment to any specific process theory. Debates regarding the contribution of
      different kinds of knowledge can be converted into statistical tests of the
      corresponding model parameters.

PMID- 15267129
TI  - The impact of informative tutoring feedback and self-efficacy on motivation and
      achievement in concept learning.
AB  - Informative tutoring feedback (ITF) provides assisted multiple response tries by
      offering strategically useful information for task completion as opposed to
      simply offering the solution. Previous studies on ITF focused on its effects on
      achievement. The present studies examine the assumption that ITF affects not only
      achievement, but also motivational variables such as task engagement, effort,
      persistence, and satisfaction with performance. In two experiments, students
      differing in self efficacy (SE) for identifying concepts worked on concept
      identification tasks. In cases of incorrect hypothesis about the concept, they
      received either outcome feedback or ITF. Results reveal that motivation and
      achievement depend on both SE and type of feedback. Future research should
      examine in more detail how ITF affects the self-enhancing processes between on
      task motivation, achievement, and self-evaluation.

PMID- 15267130
TI  - Opioid peptides, opioid receptors and mechanism of down regulation.
AB  - Biogenesis of various endogenous opioid peptides, anatomical distribution and the
      characteristics of multiple receptors with which they interact provides an
      opportunity for understanding the role of opioid systems and mechanism of opioid
      tolerance. Cellular and anatomical distribution of opioid receptor and their
      function is important for identification of neuronal systems and local network
      involved in initiation of drug action and subsequent development of adaptations
      resulting from repeated drug use. The details concerning discovery and progress
      in endogenous opioid peptide research and their distribution in brain have been
      described in this review. This review also describes opioid receptors, their
      distribution and mechanism of down regulation, which may be one of the causes for
      tolerance to opioids. Agonist induced down regulation and recent evidence for
      involvement of ubiquitin/proteasome system in this process has been discussed.

PMID- 15267131
TI  - Role of lipid and lipoprotein metabolizing enzymes in the development of
      atherosclerosis.
AB  - Cardiovascular disease is the primary cause of mortality in developed and
      developing nations. With an increase in the aging population, there is a surge in
      the incidence of atheroscleortic cardiovascular diseases. One of the most common
      and lethal manifestations of atherosclerosis is coronary heart disease,
      accounting for 50% of the atherosclerotic cardiovascular diseases in men and
      women younger than 75 years. Peripheral arterial diseases, manifested mainly as
      intermittent claudication constitute approximately 10% of the atherosclerotic
      cardiovascular events. According to the American Heart Association 2001 Heart and
      Stroke Statistical Update, atherosclerosis accounts for 75% of all deaths due to
      cardiovascular diseases. Therefore, atherosclerosis continues to remain the
      primary cause of health concern for the population at large. The aim of this
      review is to discuss the role of enzymes that are involved in the metabolism of
      lipid and lipoproteins in the development of atherosclerosis.

PMID- 15267132
TI  - Image reconstruction of optical attenuation coefficient variation in biological
      tissues.
AB  - A procedure for non-invasive imaging of the optical attenuation coefficient
      variation of in vivo thick organs/tissues is developed. The laser back-scattered
      surface profiles at various locations of human forearm, by multi-probe
      reflectometer, are measured. These profiles are matched by iterative procedure,
      with that as obtained by Monte Carlo simulation and the corresponding values of
      attenuation coefficient (equal to the sum of absorption and reduced scattering
      coefficients) are determined. By interpolation of this data a 100 x 100 grid is
      constructed and after median filtering of this data a color-coded image of the
      variability of the optical attenuation coefficient of the forearm is obtained.
      These images in different subjects show variation due to change in overall tissue
      composition and blood pooling. This non-invasive imaging procedure may help in
      identifying the diseased affected regions in healthy tissues and in application
      of photodynamic therapy.

PMID- 15267133
TI  - Role of apoptosis in photodynamic sensitivity of human tumour cell lines.
AB  - Photodynamic therapy (PDT) using a photosensitizer, such as haematoporphyrin
      derivative (HpD), in conjunction with visible light is a promising new modality
      to treat localized cancer. Cell death caused by PDT (through the generation of
      reactive oxygen species) can occur either by apoptosis (interphase death or as a
      secondary event following mitosis) and/or necrosis depending on the cell type,
      concentration and intracellular localization of the sensitizer, and the light
      dose. Since, apoptosis induced by PDT treatment plays an important role in
      determining the photodynamic efficacy, in the present work we have investigated
      the role of apoptotic cell death in relation to the observed differences in
      sensitivity to HpD-PDT between a human glioma cell line (BMG-1) carrying wild
      type tumour suppressor gene p53 and a human squamous carcinoma cell line (4451)
      with mutated p53. HpD (photosan-3; PS-3) -PDT induced apoptosis was studied by:
      [A] flow-cytometric analysis of DNA content (sub G0/G1 population); [B]
      phosphatidylserine externalization (Annexin-V +ve cells); [C] cell size and
      cytoskeleton reorganization (light-scatter analysis); and [D] fluorescence
      microscopy (morphological features). PS-3-PDT induced a significantly higher
      level of apoptosis in BMG-1 cells as compared to 4451 cells. This was dependent
      on the concentration of PS-3 as well as post-irradiation time in both the cell
      lines. At 2.5 microg/ml of PS-3 the fraction of BMG-1 cells undergoing apoptosis
      (60%) was nearly 6 folds higher than 4451 cells (10%). In BMG-1 cells the
      induction of apoptosis increased with PS-3 concentration up to 5 microg/ml
      (>80%). However, a decrease was observed at a concentration of 10 microg/ml,
      possibly due to a shift in the mode of cell death from apoptosis to necrosis. In
      4451 cells, on the other hand, the increase in apoptosis could be observed even
      up to 10 microg/ml of PS-3 (60%). Present results show that the higher
      sensitivity to PS-3-PDT in glioma cells arise on account of a higher level of
      apoptosis and suggest that induction of apoptosis is an important determinant of
      photodynamic sensitivity in certain cell types.

PMID- 15267134
TI  - Effect of oophorectomy on expression of calcium sensing receptor mRNA in rat
      duodenal mucosa.
AB  - Calcium sensing receptor (CaR) in duodenal mucosa may be involved in active
      calcium absorption. Estrogen deficiency results in decreased intestinal calcium
      absorption. Effects of bilateral oophorectomy (OVX) have been studied on calcium
      homeostasis, bone mineral density (BMD) and CaR mRNA levels in duodenal mucosa at
      4 weeks in adult female Sprague Dawley rats and compared with those in sham
      operated and control group. There was no significant change in serum corrected
      calcium, inorganic phosphorous, calcidiol and intact parathyroid hormone in all
      the three groups. OVX rats had a significant decline in serum estrogen (E2)
      levels and alkaline phosphatase. They also had a significant decrease in BMD
      (DXA) at lumbar spine in vivo, and proximal and distal tibia in vitro while there
      was no significant change in serum E2 and BMD parameters in sham-operated and
      control rats. Northern blot analysis revealed no significant change in the CaR
      mRNA expression in duodenal mucosa in all three groups. The results suggests that
      CaR mRNA expression in duodenal mucosa is not affected by physiological
      circulating concentrations of estradiol in rats.

PMID- 15267135
TI  - Involvement of GABA-A receptor chloride channel complex in isolation stress
      induced free choice ethanol consumption in rats.
AB  - The present study revealed the effect of diazepam, a benzodiazepine, and
      progesterone, a pregnane precursor of neurosteroids, which act via modulating
      GABA-A chloride channel complex on the isolation stress-induced free choice
      ethanol consumption in adult rats. Isolation stress for 24 hr over a period of 6
      days produced a significant increase in ethanol consumption, which persisted
      during the 6-day recovery period. Pretreating the animals with diazepam (5 mg/kg,
      i.p.), or progesterone (5 mg/kg, i.p.), blocked the isolation stress-induced
      increase in ethanol consumption. Bicuculline (2 mg/kg, i.p.), a GABA-A receptor
      antagonist significantly attenuated the effect of both diazepam and progesterone
      on stress-induced modulation of ethanol consumption. Isolation stress also caused
      an increase in total fluid consumption, which was antagonised by both diazepam
      and progesterone. Like ethanol consumption, this effect of diazepam and
      progesterone on isolation stress-induced increase in total fluid consumption was
      attenuated by bicuculline. Neither diazepam nor progesterone produced an increase
      in ethanol consumption in non-stressed rats. However, unlike diazepam,
      progesterone administration to non-stressed rats caused a significant increase in
      total fluid consumption. Results of the present study thus show that GABAergic
      mechanisms may be playing an important role in isolation stress-induced increase
      in ethanol consumption.

PMID- 15267136
TI  - Differential organization of a LINE-1 family in Indian pygmy field mice.
AB  - Southern blot hybridization analysis of genomic DNAs digested with restriction
      endonuclease EcoR I and Ava II from Mus musculus domesticus, Mus booduga and Mus
      terricolor with a cloned repetitive DNA fragment of Mus booduga as a probe showed
      difference in restriction pattern of this DNA in these three species. Further
      Southern analysis of the BamH I digested genomic DNAs from these species
      hybridized with cloned DNA fragment as a probe and sequencing of the cloned DNA
      revealed that this 252 bp cloned DNA fragment is a part of BamHI repeat element
      of genus Mus and is 87% homologous to the contiguous portion of the Mus musculus
      domesticus LINE-1 element. The species specific fragment pattern generated by
      different restriction endonucleases using this DNA as a probe revealed difference
      in the organization of LINE-1 repetitive element in the three species of genus
      Mus.

PMID- 15267137
TI  - Protective effect of Pongamia pinnata flowers against cisplatin and gentamicin
      induced nephrotoxicity in rats.
AB  - Ethanolic extract of flowers of Pongamia pinnata was studied for its protective
      effect against cisplatin and gentamicin induced renal injury in rats. When the
      extract (300 & 600 mg kg(-1)) was administered orally for 10 days following
      cisplatin (5 mg kg(-1) i.p.) on day 5, toxicity of cisplatin, as measured by loss
      of body weight, elevated blood urea and serum creatinine declined significantly.
      Similarly in gentamicin (40 mg kg(-1) s.c.) induced renal injury, the extract
      (600 mg kg(-1)) normalized the raised blood urea and serum creatinine levels.
      Reversal of cisplatin and gentamicin renal cell damage as induced by tubular
      necrosis ie, marked congestion of the glomeruli with glomerular atrophy,
      degeneration of tubular epithelial cells with casts in the tubular lumen and
      infiltration of inflammatory cells in the interstitium was confirmed on
      histopathological examination. In the preventive regimen, co-administration of
      the extract with gentamicin significantly prevented the renal injury both
      functionally and histologically. Ethanolic extract of flowers had a marked nitric
      oxide free radical scavenging effect, suggesting an antioxidative property. Two
      flavonoids, known for their antioxidant activity viz. kaempferol and 3, 5, 6, 7,
      8-pentamethoxy flavone were isolated from the extract. The results suggested that
      the flowers of Pongamia pinnata had a protective effect against cisplatin and
      gentamicin induced renal injury through antioxidant property.

PMID- 15267138
TI  - Production of thiophenes from callus cultures of Tagetes patula L. and its
      mosquito larvicidal activity.
AB  - Calli were initiated from leaf tissues of T. patula, on Murashige and Skoog's
      medium supplemented with 2-4 dichlorophenoxacetic acid (2,4-D) and kinetin (Kn).
      The maximum accumulation of biomass was recorded on 6th week at 1.11 g. dry
      wt/culture. Maximum thiophene content was recorded on 4th week at 0.008% on dry
      wt basis in callus cultures of T. patula subjected to nutrient stress. Nitrogen
      stress induced 3-fold increase in thiophene production level in six weeks (0.024%
      on dry weight basis). The best hormonal supplementation required for thiophenes
      production was found to be 2,4-D (2.0 mg L(-1)) and kinetin (2.0 mg L(-1)). The
      thiophenes produced in callus cultures of T. patula showed larvicidal effect
      against mosquito larvae.

PMID- 15267139
TI  - Establishment of embryonic cultures and somatic embryogenesis in callus culture
      of guggul-Commiphora wightii (Arnott.) Bhandari.
AB  - Somatic embryogenesis in callus cultures of Commiphora wightii (Arnott.) Bhandari
      was achieved. Though the frequency of explants producing embryonic culture was
      low, immature zygotic embryos were the only suitable explants to produce
      embryonic callus after reciprocal transfers on media containing 2,4,5
      trichlorophenoxy acetic acid (0.1 mgl(-1)) and kinetin (0.1 mgl(-1)) or devoid of
      growth regulators. All other media failed to produce embryonic callus. Embryonic
      cells were small, densely filled with cytoplasm and isodiametric as compared to
      non-embryonic cells, which were large, elongated and vacuolated. Maximum growth
      of embryonic callus was recorded on modified MS medium (MS-2 medium) supplemented
      with BA (0.25 mgl(-1)) and IBA (0.1 mgl(-1)). MS-2 salts supported higher growth
      of callus as compared to tissues grown on B5 medium containing same
      concentrations of plant growth regulators. Exogenous medium nutrients had no
      effect on somatic embryo development whereas plant growth regulators had little
      effect. Asynchronously growing embryos formed plantlets regularly which were
      successfully transferred to the field conditions.

PMID- 15267140
TI  - Effect of phenol on ultra structure and plasmid DNA of Xanthomonas oryzae pv.
      oryzae.
AB  - Most phenolic substances of plant origin are toxic to microorganisms and they
      confer some degree of protection to plants against phytopathogens. Xanthomonas
      oryzae pv. oryzae, bacterial blight pathogen of rice (Oryza sativa) was treated
      with phenol (monohydroxy benzene) and its effects on the morphology and
      cytological changes of the bacterium were studied. Total lysis of cells occurred
      with 5 mM conc of phenol while at 2 mM conc, the cell walls became rough and cell
      contents started shrinking. Plasmids isolated from both treated (2 mM) and
      control cells did not show any marked difference under electron microscope except
      that they differed in their quantity and might influence pathogenicity.

PMID- 15267141
TI  - Predation and searching efficiency of a ladybird beetle, Coccinella
      septempunctata Linnaeus in laboratory environment.
AB  - The predation and searching efficiency of fourth instar of predatory C.
      septempunctata at various densities of mustard aphid, Lipaphis erysimi
      (Kaltenbach) and predator was investigated under laboratory conditions. The
      feeding rate of predatory stage decreased at increased prey- and predator
      densities. Highest percent (92.80%) prey consumption was observed at initial prey
      density and lowest percent (40.86%) prey consumption at highest prey density by
      the fourth instar, though the total prey consumption increased with increase in
      either prey- or predator densities. Similarly, the individual prey consumption
      was also highest at initial predator density and lowest at highest predator
      density owing to the mutual interference between the predators at higher
      densities. The area of discovery (searching efficiency) also decreased with
      increase in prey- and predator densities. Handling time of predator was highest
      at lower prey densities, which decreased with increased prey densities. The
      highest percentage of prey consumption at the prey density of 50 revealed that
      1:50 predator-prey ratio was the best to reduce the pest population.

PMID- 15267142
TI  - Protective effect of Lawsonia alba Lam., against CCl4 induced hepatic damage in
      albino rats.
AB  - The oral administration in varying doses of aqueous suspension of extract of L.
      alba, bark extract to rats for 10 days afforded good hepatoprotection against
      CCl4 induced elevation in serum marker enzymes, serum bilirubin, liver lipid
      peroxidation and reduction in total serum protein, liver glutathione, glutathione
      peroxidase, glutathione-s-transferase, glycogen, superoxide dismutase and
      catalase activity. The results suggest hepatoprotective and antioxidant activity
      of extract of L. alba bark.

PMID- 15267143
TI  - Effect of onion (Allium cepa Linn.) and garlic (Allium sativum Linn.) on plasma
      triglyceride content in Japanese quail (Coturnix coturnix japonicum).
AB  - Dietary onion and garlic caused an increase in the level of plasma triglyceride
      which could be due to insulin like activity of dietary alliums and other factors
      that promote lipogenesisi in growing stages. Changes in the plasma triglyceride
      level in the control group due to change in age and sex were also noted. The
      triglyceride level was more in female birds when compared to males of similar age
      group. The plasma trigelyceride level increased with age in both sex except for
      the level being similar in the 6 and 9-week old females and 3 and 6-week old male
      birds. The results suggest that the effects of alliums in growing and adult
      stages may be different which needs further study.

PMID- 15267144
TI  - Enhanced esterase activity in salivary gland and midgut of Aedes aegypti mosquito
      infected with dengue-2 virus.
AB  - Mosquitoes were infected by intrathoracic inoculation. About 95% head squashes
      were positive for dengue virus antigen on the 15th post infection day (PID).
      Esterase activity was determined in the homogenates prepared from the salivary
      glands and midguts on different PIDs of dengue virus inoculated and control
      mosquitoes showed that it was consistently higher in the virus-infected batches.

PMID- 15267145
TI  - Alterations in polypeptides pattern in malaria vector Anopheles stephensi, fed
      upon immunized blood causing fecundity reduction.
AB  - Changes in polypeptides pattern of haemolymph, midgut, ovary and salivary glands
      of female mosquito A. stephensi were studied when fed upon anti-mosquito
      haemolymph antibodies. The expression of almost all polypeptides was reduced in
      haemolymph and ovary of the immune fed mosquitoes as compared to control.
      However, there was no significant difference in case of midgut and salivary
      glands. Seven polypeptides 100, 90, 84, 80, 62, 19 and 12.5 kDa were absent in
      haemolymph and five 92, 90, 80, 60 and 55 kDa were absent in ovaries. Changes in
      the polypeptide pattern have been correlated with the fecundity reduction due to
      immunized blood feeding.

PMID- 15267146
TI  - Fighting cancer in the information age: the role of Internet.
AB  - Cancer is a major health problem worldwide which is likely to assume alarming
      proportions in the next two decades. Communication and information have
      increasingly been considered important in helping people to cope with cancer. The
      arrival of Internet offers the opportunity to fundamentally reinvent medicine and
      health care delivery. Medical professionals can now use the Internet for
      continuing medical education, access latest medical information, for fast
      confirmation of diagnosis, exchange opinion on treatment strategies and in
      palliative care. Internet can provide cost-effective and timely ways to deliver a
      complex mix of interesting and high-quality information and expertise to cancer
      patients. Patients can also independently search the Internet to know about their
      illness and treatment options. However, of concern is the quality of information
      that is available in the 'Net'. Some Internet sites may contain erroneous
      information on cancer and can pose serious problems. There are also many good
      sites, which provide quality information on cancer for medical professionals,
      researchers and patients. This article focuses on how the Internet will aid us in
      fight against cancer.

PMID- 15267147
TI  - Sinusoidal electromagnetic field of 50 hz helps in retaining calcium in tibias of
      aged rats.
AB  - Effect of 50Hz sinusoidal electromagnetic field (SEMF) on normal bone physiology
      was evaluated in young and old female and male Wistar rats. Exposure to SEMF
      resulted in increased 45Ca retention in tibias of aged animals only. Levels of
      serum calcium in young female and male rats were significantly less than in
      respective aged rats. These were further decreased after 4 weeks of SEMF
      exposure. SEMF exposure did not change the serum calcium levels in aged rats, and
      inorganic phosphates in young and aged animals. Similarly, the levels of tartrate
      resistant acid and alkaline phosphatase were significantly decreased in young
      rats, whereas the levels remained unchanged in aged rats of either sex. The
      results revealed that SEMF of 1mT can prevent bone calcium loss due to aging in
      animals.

PMID- 15267148
TI  - Studies on kinetic properties of acid phosphatase from nuclei-free rat liver
      homogenate using different substrates.
AB  - Kinetic properties of rat liver acid phosphatase were evaluated using the
      conventional synthetic substrates sodium beta glycerophosphate (betaGP) and p
      nitrophenyl phosphate (PNPP) and physiologically occurring phosphate esters of
      carbohydrates, vitamins and nucleotides. The extent of hydrolysis varied
      depending on the substrates; phosphate esters of vitamins and carbohydrates were
      in general poor substrates. Kinetic analysis revealed the presence of two
      components of the enzyme for all the substrates. Component I had low Km and low
      Vmas. Opposite was true for component II. The Km values were generally high for
      betaGP, PNPP and adenosine diphosphate (ADP). Amongst the nucleotides substrates
      AMP showed high affinity i.e. low Km. The increase in enzyme activity in general
      at high substrate concentration seems to be due to substrate binding and positive
      cooperativity. AMP which showed highest affinity was inhibitory at high
      concentration beyond 1 mM. The results suggest that in situ the nucleotides may
      be the preferred substrates for acid phosphatase.

PMID- 15267149
TI  - Histological changes in intestine in semichronic diarrhoea induced by lactose
      enriched diet in rats: effect of Diarex-Vet.
AB  - Efficacy of Diarex-Vet (The Himalaya Drug Company, Makali, Bangalore, India) was
      evaluated histologically in semichronic diarrhoea induced by lactose enriched
      diet in rats. The rats in different groups were given lactose enriched diet alone
      for 2 days before starting the treatment with Diarex-Vet at a dose of 250, 500
      and 750 mg/kg body weight along with lactose enriched diet for 5 days. Animals
      were euthanised at the end of 5 days of treatment and histological changes were
      observed in the ileum, caecum and colon. Semiquantitative analysis of goblet
      cells in intestines showed dose dependent response among the treated groups. The
      morphological changes were comparable to normal in the group given 750 mg/kg body
      wt Diarex-Vet. The effects observed were attributed to the lactase like analogous
      activity of Diarex-Vet or the inhibition of the osmotic processes in the
      intestinal lumen thereby reducing the morphological changes in the intestines.

PMID- 15267150
TI  - Inhibition of mutagenicity of food-derived heterocyclic amines by sulforaphane--a
      constituent of broccoli.
AB  - Sulforaphane, a constituent of broccoli was investigated for its antimutagenic
      potential against different classes of cooked food mutagens (heterocyclic
      amines). These include imidazoazaarenes such as 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP); pyridoindole derivatives such as 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp-P-2); and, dipyridoimidazole derivative such as 2-amino-6
      methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1). Tests were carried out by Ames
      Salmonella/reversion assay using Salmonella typhimurium TA98 (frame shift
      mutation sensitive) and TA100 (base pair mutation sensitive) bacterial strains in
      the presence of Aroclor 1254-induced rat liver S9. Results of these in vitro
      antimutagenicity studies strongly suggest that sulforaphane is a potent inhibitor
      of the mutagenicity induced by imidazoazaarenes such as IQ, MeIQ and MeIQx
      (approximately 60% inhibition) and moderately active against pyridoindole
      derivatives such as Trp-P-1 and Trp-P-2 (32-48% inhibition), but ineffective
      against dipyridoimidazole derivative (Glu-P-1) in TA 100.

PMID- 15267151
TI  - Melatonin produced metabolic changes in testis and did not prevent indomethacin
      induced testicular lipid peroxidation in adult rat.
AB  - Melatonin was orally given to rats at the dosage of 0.75 mg/rat/day for 7 days
      and challenged on the day 7 with a single toxic dose of indomethacin (20 mg/kg,
      intramuscularly) to test either protection afforded by melatonin against
      indomethacin-induced oxidative tissue damage or effects of repeated
      administration of this hormone on some testicular metabolic parameters. The
      results showed increased lipid peroxidation, as evidenced by the formation of
      thiobarbituric acid reactive substances, accompanied by non-significantly
      decreased glutathione content in the testis of rats treated with indomethacin.
      However, prior administration of melatonin failed to prevent indomethacin-induced
      testicular lipid peroxidation. No change in the production of lipid peroxidation
      and glutathione was observed as well after treatment with melatonin alone.
      Meanwhile, exogenous melatonin inhibited testicular levels of total lipid, total
      protein, and activity of aspartate aminotransferase, alanine aminotransferase,
      and alkaline phosphatase. All treated rats exhibited unchanged activity of both
      acid phosphatase and lactate dehydrogenase. The results indicated inability of
      oral administration of melatonin to prevent some of the oxidative damaging
      effects of indomethacin in the rat testis. In addition, the study provided an
      evidence that melatonin has an inhibitory action on the testicular metabolism in
      adult rats and thereby suggests a possible role of this hormone in modulating
      functions of rat testis.

PMID- 15267152
TI  - Effect of disinfectants on stability and transmissibility of R-plasmid in E. coli
      isolated from drinking water.
AB  - Drug resistant enteropathogenic E. coli (EPEC, 086 serotype) isolated from
      contaminated piped drinking water supply (Fecal coliform 160/100 ml) was studied
      for effect of disinfectants (chlorine and UVB) on stability and transmissibility
      of R-plasmid. The strain was resistant to streptomycin and bacitracin and
      tolerant to multiple metal ions of Cd, Cr, Co, As, Ni, Zn and Hg. A plasmid of
      molecular size of 3.7 Kb was detected in the organism. After exposure to
      sublethal doses of disinfectants, complete elimination of resistances to
      streptomycin and Cr was observed. Partial loss of resistance to Hg due to
      chlorine was detected. Although UVB did not effected the pattern of
      transmissibility effect on frequency of transfer was observed. Surprisingly, in
      UVB irradiated cells, significantly enhanced rate of transfer was noted.

PMID- 15267153
TI  - Mentha piperita (Linn.) leaf extract provides protection against radiation
      induced chromosomal damage in bone marrow of mice.
AB  - Oral administration of M. piperita (1 g/kg body weight/day) before exposure to
      gamma radiation was found to be effective in protecting against the chromosomal
      damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma
      radiation showed chromosomal aberrations in the form of chromatid breaks,
      chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments.
      There was a significant increase in the frequency of aberrant cells at 6 hr after
      irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation
      autopsy time. Further, the frequency of aberrant cells showed decline at late
      post-irradiation autopsy time. However, in the animals pretreated with Mentha
      extract, there was a significant decrease in the frequency of aberrant cells as
      compared to the irradiated control. Also significant increase in percentage of
      chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges,
      acentric fragments, total aberrations and aberrations/damaged cell was observed
      at 12 hr post-irradiation autopsy time in control animals, whereas Mentha
      pretreated irradiated animals showed a significant decrease in percentage of such
      aberrations. A significant decrease in GSH content and increase in LPO level was
      observed in control animals, whereas Mentha pretreated irradiated animals
      exhibited a significant increase in GSH content and decrease in LPO level but the
      values remained below the normal. The radioprotective effect of Mentha was also
      demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from
      the present study suggest that Mentha pretreatment provides protection against
      radiation induced chromosomal damage in bone marrow of Swiss albino mice.

PMID- 15267154
TI  - Wound healing property of ethanolic extract of leaves of Hyptis suaveolens with
      supportive role of antioxidant enzymes.
AB  - Ethanolic extract of leaves of Hyptis suaveolens was evaluated for its wound
      healing activity in ether-anaesthetized Wistar rats at two different doses (400
      and 800 mg/kg) using incision, excision, and dead space wound model. Significant
      increase in skin breaking strength, granuloma breaking strength, wound
      contraction, hydroxyproline content and dry granuloma weight and decrease in
      epithelization period was observed. A supportive study made on granuloma tissue
      to estimate the levels of catalase and superoxide dismutase recorded a
      significant increase in the level of these antioxidant enzymes. Granuloma tissue
      was subjected to histopathological examination to determine the pattern of lay
      down for collagen using Van Gieson and Masson Trichrome stains. Enhanced wound
      healing activity may be due to free radical scavenging action of the plant and
      enhanced level of antioxidant enzymes in granuloma tissue. Better collagenation
      may be because of improved antioxidant studies.

PMID- 15267155
TI  - A comparative study of allitin and garlic on lipid turnover in a teleost, Anabas
      testudineus (Bloch).
AB  - Both allitin and garlic have anti-lipogenic properties substantiated by the
      activity of three lipogenic enzymes and lipid profiles. The rise in the HDL
      levels and simultaneous fall in the LDL upon garlic intake is the most convincing
      indicator of reduced lipid concentration. However, the administration of allitin
      recorded a decrease in the HDL and LDL levels, but when calculated on a
      percentage basis, there was a marginal increase in the HDL level. On the basis of
      results, it can be concluded that garlic or its derivatives have hypolipidaemic
      effect in submammalian vertebrates also. The cholesterol lowering effect of
      allitin and garlic can be commercially exploited for producing fish with low
      cholesterol for possible human consumption.

PMID- 15267156
TI  - Chitin degrading potential of bacteria from extreme and moderate environment.
AB  - Five hundred chitin-degrading bacteria were isolated from 20 different locations.
      High percentage of potent chitin-degraders was obtained from polluted regions.
      Potent chitin-degrading bacteria were selected by primary and secondary
      screening. Among the selected isolates, 78% were represented by the genus
      Streptomyces. Majority of the isolates had good chitinolysis relative to the
      growth although isolates with better growth were also seen. Such isolates are
      important for the production of SCP from chitinous wastes. The potent isolates
      belonged to the genera Streptomyces, Kitasatosporia, Saccharopolyspora,
      Nocardioides, Nocardiopsis, Herbidospora, Micromonospora, Microbispora,
      Actinoplanes, Serratia, Bacillus and Pseudomonas. This study forms a
      comprehensive base for the study of diversity of chitinolytic systems of
      bacteria.

PMID- 15267157
TI  - Immuno-pathotyping of Karnal bunt (Tilletia indica) isolates of wheat using anti
      mycelial antibodies.
AB  - Two types of polyclonal antibodies raised against whole lyophilized (LMA) and
      fractionated mycelial antigen (FMA) of most virulent, Pantnagar isolate of T.
      indica were used for the development of immunoassay systems, viz. dot immuno
      binding assay (DIBA) and indirect enzyme linked immuno-sorbent assay (ELISA)
      procedures. The immuno-assays were developed by performing antigen concentration
      kinetics and antibody dilution curves analyses. These assays were employed for
      immuno-analysis of diversity amongst KB pathogen based on antibodies reactivity
      pattern and subsequently categorization into distinct sero-groups. The reactivity
      of two polyclonal antibodies was tested with 15 (P1-P15) isolates of T. indica.
      When anti-LMA antibodies were tested, four serologically distinct groups were
      formed based on percent reactivity (>75%, highly reactive; 60-75%; moderately
      reactive, <50-25%; low reactive and <25%, non-reactive). However, when anti-FMA
      antibodies were used, two distinct sero-groups were formed based on reactivity
      patterns (group I, highly reactive P1, P3, P4, P11 and P13, group II, less
      reactive P2, P4, P5, P6, P7, P8, P9, P10, P12, P14 and P15).

PMID- 15267158
TI  - High frequency axillary bud multiplication and ex vitro rooting of Wedelia
      chinensis (Osbeck) Merr.--a medicinal plant.
AB  - An efficient protocol was achieved for rapid propagation of Wedelia chinensis
      (Osbeck) Merr. through axillary bud proliferation and ex vitro rooting. Murashige
      and Skoog (MS) medium supplemented with benzyladenine (BA; 8.87 microM) and
      indole-3-butyric acid (IBA; 2.46 microM) was optimal for axillary bud
      proliferation, which developed a mean of 8.3 shoots/node. Excision and culture of
      node segments from in vitro shoots on medium supplemented with the same
      concentration of growth regulators developed more than 30 shoots within 40 days.
      Excision and culture of nodes in succession enhanced the number of shoots. Shoot
      multiplication did not exhibit decrease in the number of shoots even at 10th
      subculture. Nevertheless, the shoots exhibited a tendency towards stunted nature.
      But reduction of BA to 4.44 or 2.22 microM resumed normal growth of shoots. Half
      strength MS medium fortified with IBA (2.46 microM) induced the highest number of
      roots. All in vitro rooted shoots survived in field. Dipping of the basal end of
      shoots collected from multiplication medium in IBA (2.46 microM) solution for 7
      days induced roots and its transfer to small pots facilitated the survival of all
      rooted shoots (100%). Rooting ex vitro by direct transfer of shoots from
      multiplication medium exhibited 89.2 per cent survival. Use of commercial sugar
      and tap water and also the omission of in vitro rooting reduce the propagation
      cost 50-70 per cent. The protocol enables to harvest more than 50,000 plantlets
      within 150 days starting from a single node explant.

PMID- 15267159
TI  - Antioxidant tolerance of kidney after irradiation.
AB  - Different doses of irradiation were performed in which group 1 (non-irradiated),
      group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body)
      were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid
      peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in
      the whole kidney. The MDA content increased in animals irradiated with 8 and 15
      Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in
      group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when
      compared with control group. The activity of GSH-Px decreased significantly in
      group 2 and group 3 in comparison to controls. It may be concluded that a high
      dose of ionizing irradiation cause excessive oxidative stress in kidney.

PMID- 15267160
TI  - Gender differences in predator induced pain perception in rats.
AB  - Pain is an unpleasant sensation. It warns the living being about the impending
      damage to the tissues. The perception of pain is influenced by physical and
      psychological factors. The impact of chronic intermittent psychological stress on
      pain perception and the differences in antinociceptive responses have been
      studied in male and anestrous female albino rats. Fifteen rats in each group were
      subjected to psychological stress, by exposing them to their natural predator-
      cat, for a duration of 20 min daily for 12 consecutive days. Tail flick response
      latency to radiant heat was used as a measure to evaluate pain perception. It was
      observed that both the groups had a relatively high pain threshold at the
      beginning of exposure schedule due to the modulation of opioid analgesic system
      by the higher level of circulating testosterone in males and low level of
      estrogen in anaestrous females. However, the threshold for pain perception showed
      a gradually declining trend in both the groups over the next 11 days to reach the
      control values. This increase in sensitivity to pain or decreased pain threshold
      could be attributed to the phenomenon of habituation.

PMID- 15267161
TI  - Association of cucumovirus and potyvirus with betelvine (Piper betle L.) as
      evidenced by ELISA and RT-PCR.
AB  - An attempt was made to detect various viruses of Piper betle grown at Mahoba and
      Banthara in India. DAC-ELISA and RT-PCR tests were performed in leaf sap samples
      of betelvine for detection of a cucumovirus (Cucumber mosaic virus) and potyvirus
      (Bean yellow mosaic virus) using specific antibodies and universal primers of
      respective viruses. DAC-ELISA could detect only CMV. However, RT-PCR detected
      both cucumovirus and potyvirus infection in betelvine samples. Association of CMV
      with betelvine was observed for the first time in the present study.

PMID- 15267162
TI  - Time for change--time to engage.

PMID- 15267163
TI  - The role of the senior health care worker in critical care.
AB  - This article identifies that the introduction of the support worker role in the
      critical care team facilitates flexibility when organizing and managing patient
      care. Qualified nurses' time can be used more effectively, enhancing the quality
      of the patient care delivered. Aspects of the qualified nurses' workload in
      critical care can be shared and delegated successfully to unqualified staff. It
      is our view that staffing levels in critical care environments need to be
      reviewed with more flexible working practices to meet the current and future
      demands of critical care. There is a need for national consensus amongst
      qualified nurses to clarify and define the role of the support worker and develop
      a critical care competency framework to standardize training. To ensure
      proficiency, adequate training and appropriate accountability, support workers
      require regulation by a nationally recognized body.

PMID- 15267164
TI  - Education and training for acute care delivery: a needs analysis.
AB  - Technological and clinical advances have led to increased levels of patient
      dependency and shorter hospital stay, such that they are now often managed on
      general wards. Have staff been trained or educated for this change in focus? This
      project was designed to identify the education and training needs of health care
      professionals in assessing and managing acutely physically ill hospital patients,
      within the boundaries of one Strategic Health Authority (SHA) in the UK.
      Participants identified the knowledge, skills and resources required to assess
      and manage acutely ill patients. These issues may be addressed through the
      provision of an appropriate range of structured educational programmes and
      experiences with the ultimate aim of improving standards of patient care.

PMID- 15267165
TI  - Continuing professional development: does it make a difference?
AB  - Continuing professional development (CPD) is costly in terms of both
      organizational resources and personal time and effort. It forms an important part
      of the strategy for modernizing the health service and is an expectation of
      qualified nurses. There is little evidence to demonstrate the impact of CPD in
      terms of improved patient care and services. A small pilot study was undertaken.
      A group of intensive therapy unit (ITU) managers developed a goal attainment
      scale (GAS) to evaluate the impact of an ITU course. Results suggest that the ITU
      course did make a difference to the development of ITU nurses, but the nurses who
      did not take the course also developed. This has implications for service
      providers and educationalists in terms of expectations, timing and content of
      courses. The GAS was a useful tool as an approach to evaluating the impact of CPD
      but requires more rigorous testing before it can be described as reliable and
      valid.

PMID- 15267166
TI  - Patients' dreams and unreal experiences following intensive care unit admission.
AB  - Dreams and unreal experiences occur commonly in critically ill patients admitted
      to intensive care unit. This study describes 31 patients' dreams and explores the
      relationship between patients' subjective recall 12-18 months after intensive
      care unit discharge and their observed behaviour during their intensive care unit
      stay. Semi-structured interviews revealed that 74% of longer-term ICU patients (>
      or = 3 days) reported dreaming, with the majority also describing frightening
      hallucinations. Only two patients reported long-term negative psychological
      sequelae, but the short-term consequence of hallucinations may also have an
      undiscovered impact on patients' recovery.

PMID- 15267167
TI  - Aesthetic physical caring--valuing the visible.
AB  - The aim of this article was to define the term 'aesthetics' in order to
      demonstrate that aesthetic physical caring is administered to the intensive care
      patient. Johns's model of structured reflection (10th version) was used to
      reflect upon three nursing narratives with intensive care unit nurses and
      relatives and reveals why physical caring is fundamental for the patient.

PMID- 15267168
TI  - Metal ion effects on ion channel gating.
AB  - Metal ions affect ion channels either by blocking the current or by modifying the
      gating. In the present review we analyse the effects on the gating of voltage
      gated channels. We show that the effects can be understood in terms of three main
      mechanisms. Mechanism A assumes screening of fixed surface charges. Mechanism B
      assumes binding to fixed charges and an associated electrostatic modification of
      the voltage sensor. Mechanism C assumes binding and an associated non
      electrostatic modification of the gating. To quantify the non-electrostatic
      effect we introduced a slowing factor, A. A fourth mechanism (D) is binding to
      the pore with a consequent pore block, and could be a special case of Mechanisms
      B or C. A further classification considers whether the metal ion affects a single
      site or multiple sites. Analysing the properties of these mechanisms and the vast
      number of studies of metal ion effects on different voltage-gated on channels we
      conclude that group 2 ions mainly affect channels by classical screening (a
      version of Mechanism A). The transition metals and the Zn group ions mainly bind
      to the channel and electrostatically modify the gating (Mechanism B), causing
      larger shifts of the steady-state parameters than the group 2 ions, but also
      different shifts of activation and deactivation curves. The lanthanides mainly
      bind to the channel and both electrostatically and non-electrostatically modify
      the gating (Mechanisms B and C). With the exception of the ether-a-go-go-like
      channels, most channel types show remarkably similar ion-specific sensitivities.

PMID- 15267169
TI  - Geometry of the DNA strands within the RecA nucleofilament: role in homologous
      recombination.
AB  - Homologous recombination consists of exchanging DNA strands of identical or
      almost identical sequence. This process is important for both DNA repair and DNA
      segregation. In prokaryotes, it involves the formation of long helical filaments
      of the RecA protein on DNA. These filaments incorporate double-stranded DNA from
      the cell's genetic material, recognize sequence homology and promote strand
      exchange between the two DNA segments. DNA processing by these nucleofilaments is
      characterized by large amplitude deformations of the double helix, which is
      stretched by 50% and unwound by 40% with respect to B-DNA. In this article,
      information concerning the structure and interactions of the RecA, DNA and ATP
      molecules involved in DNA strand exchange is gathered and analyzed to present a
      view of their possible arrangement within the filament, their behavior during
      strand exchange and during ATP hydrolysis, the mechanism of RecA-promoted DNA
      deformation and the role of DNA deformation in the process of homologous
      recombination. In particular, the unusual characteristics of DNA within the RecA
      filament are compared to the DNA deformations locally induced by architectural
      proteins which bind in the DNA minor groove. The possible role and location of
      two flexible loops of RecA are discussed.

PMID- 15267170
TI  - Medullary thyroid carcinoma.

PMID- 15267171
TI  - Expression of platelet-derived growth factor in the developing cochlea of rats.
AB  - OBJECTIVE: Platelet-derived growth factor (PDGF) is involved in the control of
      cell proliferation, differentiation and survival in various tissues of
      vertebrates. However, little is known about the expression of PDGF in the
      developing cochlea of rodents. MATERIAL AND METHODS: We examined the expression
      of PDGF family genes in the developing cochlear tissue of rats using microarrays
      and tested their role in the proliferation of progenitor hair cells using
      cellular and molecular biology techniques. RESULTS: It was found that the genes
      for PDGF-A, PDGF receptor (R)-alpha and PDGFR-beta were highly expressed in the
      rapidly growing otocyst on embryonic Days 12-14 and weakly expressed thereafter.
      Reverse transcriptase polymerase chain reaction demonstrated the expression of
      PDGF-C and confirmed the expression of PDGF-A and PDGFR-alpha and -beta in the
      developing cochlear tissue of rats and the cultured progenitor hair cells.
      Inhibition of the expression of PDGFs in the cultured progenitor hair cells with
      antisense oligonucleotides reduced the DNA synthesis. CONCLUSION: PDGFs and their
      receptors may play a role in the proliferation of developing cochlear hair cells.

PMID- 15267172
TI  - Co-expression of different angiogenic factors in external auditory canal
      cholesteatoma.
AB  - OBJECTIVE: Although external auditory canal cholesteatoma (EACC) was first
      described in 1850, its cause remains surprisingly unclear. Angiogenesis, the
      formation of new blood vessels, is essential to normal development and wound
      healing in adults. Abnormal regulation of angiogenesis has been implicated in the
      pathogenesis of several disorders. The aim of this study was to analyse
      angiogenesis regulator expression in EACC. MATERIALS AND METHODS: Cryostat
      sections of 13 investigated EACC tissue samples and normal control tissue were
      immunostained for angiogenic hepatocyte growth factor (HGF)/scatter factor (SF),
      its c-Met receptor and vascular endothelial growth factor (VEGF) using a standard
      streptavidin-biotin complex procedure. Staining against von Willebrand factor
      (vWF) served as an endothelial marker. Statistical analysis was performed
      semiquantitatively. RESULTS: The assayed angiogenic factors were all present in
      the EACC tissue, and partly overexpressed. vWF was detected in the apical layers
      of the matrix epithelium. Positive immunoreactivity for c-Met and VEGF was
      detectable in all layers of the EACC epithelium; however, adjacent tissue did not
      express c-Met and VEGE. HGF/SF was predominantly expressed in the adjacent
      perimatrix tissue and fibroblasts in particular were stained positive.
      CONCLUSIONS: The presence of vWF in the apical part of the matrix depicted the
      attempt at angiogenesis in this part of the EACC. The detection of VEGF and c-Met
      in the epithelial part of the EACC implied that their origin may be epithelial,
      while HGF/SF may be secreted or stored in the adjacent mesenchymal EACC tissue.
      The angiogenic factors investigated seem to play an important role in
      establishing that EACC occurs by modulation of angiogenesis.

PMID- 15267173
TI  - Myosin heavy chain composition of rat middle ear muscles.
AB  - OBJECTIVE: To quantitatively analyze myosin heavy chain (MHC) mRNA composition in
      two rat middle ear muscles (the tensor tympani and stapedius) using competitive
      polymerase chain reaction (PCR). MATERIAL AND METHODS: An exogenous template,
      including oligonucleotide sequences specific for the seven rat MHCs (2A, 2B, 2X,
      2L/EOM, embryonic, neonatal and beta-cardiac) as well as beta-actin, was
      constructed and used as the competitor. RESULTS: The tensor tympani and stapedius
      contained all MHC isoforms except 2L. The tensor tympani contained approximately
      equal proportions of 2X (40.4% +/- 6.5%) and 2A (34.0% +/- 1.3%) MHCs, with a
      smaller percentage of 2B (16.6% +/- 1.5%) and neonatal (7.5% +/- 0.6%) MHCs,
      while beta-cardiac and embryonic MHCs were minimally expressed. The stapedius
      contained predominantly 2X (58.0% +/- 4.2%) and 2A (32.3% +/- 6.7%) MHCs, with a
      smaller percentage of 2B (7.4% +/- 0.2%) and beta-cardiac (1.9% +/- 0.1%) MHCs.
      Neonatal and embryonic MHCs were detected at very low levels. CONCLUSION: These
      results suggest that two middle ear muscles, which are mainly composed of two
      fast-twitching myosins (2X and 2A MHCs), contract fast and are fatigue-resistant.

PMID- 15267174
TI  - Possible relationship between tympanosclerosis and atherosclerosis.
AB  - OBJECTIVE: In order to confirm a possible link, as suggested by a recent study,
      between atherosclerosis and tympanosclerosis, and which could theoretically open
      new frontiers in the early diagnosis of vascular atherosclerotic diseases
      starting from a rather simple and rapid examination such as otoscopy, we further
      investigated this hypothesis in a population affected by atherosclerotic disease
      of the carotid artery. MATERIAL AND METHODS: Fifty patients submitted to carotid
      endarterectomy were examined. Patients with a history of previous otologic
      diseases or otosurgical procedures were excluded. The presence of
      tympanosclerosis was defined if at least 20% of the eardrum was affected by
      tympanic plaques. The study group was compared to a sex- and age-matched control
      group randomly chosen from our hospital with a negative history of vascular and
      otologic diseases. RESULTS: Tympanosclerosis was observed in 18/50 patients (36%)
      in the study group, compared to 6/50 cases in the control group (12%). This
      difference was statistically significant (p = 0.005). In both groups the
      incidence of this finding was similar for both sexes. CONCLUSIONS: Our results
      confirm the reported analogies between tympanosclerosis and atherosclerosis.
      Although further investigations are needed, promising implications can be
      predicted for the diagnostic and therapeutic evaluation of this kind of ear
      patient.

PMID- 15267175
TI  - MRI versus CT in assessment of cochlear patency in cochlear implant candidates.
AB  - OBJECTIVE: To investigate how cochlear patency as seen on preoperative CT and MRI
      scans correlates with findings at surgery in cochlear implant patients. MATERIAL
      AND METHODS: CT and MRI scans of 25 patients were reviewed by 3 independent
      observers. The reviewers classified the cochlear patency and recorded the
      location of any suspected decrease in patency. Their results were compared with
      the findings noted during surgery. RESULTS: Decreased cochlear patency was found
      in six patients at surgery. The mean sensitivity/specificity of CT and MRI
      assessment was 33%/88% and 41%/91%, respectively. CONCLUSION: Our study suggests
      that CT, using axial and semi-longitudinal planes, is equivalent to MRI in
      predicting cochlear patency.

PMID- 15267176
TI  - Objective measurements of auditory nerve recovery function in nucleus CI 24
      implantees in relation to subjective preference of stimulation rate.
AB  - OBJECTIVE: Setting the optimal rate of stimulation for individual cochlear
      implant recipients is critical to the successful functional outcome of cochlear
      implantation. In the absence of an objective methodology, cochlear implants are
      currently fitted by means of a time-consuming (and therefore expensive) trial-and
      error process of limited accuracy. The aim of this study was to evaluate a
      possible relationship between the patient's subjectively preferred stimulation
      rate and an objective measurement of auditory nerve recovery time. MATERIAL AND
      METHODS: Eleven recipients of Nucleus CI 24 implants initially fitted with a
      speech processor using the advanced combination encoders speech-coding strategy
      at a rate of 900 Hz were introduced to 2 other stimulation rate options, 1200 and
      1800 Hz, at 2 different fitting sessions and were asked to choose their preferred
      rate. Preferences were compared with objective measurements of auditory nerve
      recovery time obtained with the refractory recovery function of neural response
      telemetry. RESULTS: The auditory nerve recovery time for individuals with a
      subjective preference for a slow stimulation rate was longer than that for
      individuals who preferred a fast stimulation rate, with significant differences
      between the 2 groups for 3 of the tested electrodes (Nos. 7, 11 and 15): p =
      0.024, 0.009 and 0.03, respectively (Mann-Whitney test). CONCLUSIONS: The
      association observed between subjective stimulation rate preference and
      measurements of auditory nerve recovery time indicates that the measured auditory
      nerve recovery time can be used as a reliable predictor for setting up a basic
      stimulation rate of a particular individual's map, thus reducing the cost of the
      technology and significantly increasing its effectiveness.

PMID- 15267177
TI  - Dynamics of the vestibulo-ocular reflex in patients with the horizontal
      semicircular canal variant of benign paroxysmal positional vertigo.
AB  - OBJECTIVE: Two types of direction-changing positional nystagmus, the geotropic
      and apogeotropic variants, are observed in patients with the horizontal
      semicircular canal (HSCC) type of benign paroxysmal positional vertigo (H-BPPV).
      In this study, we assessed the dynamics of the vestibulo-ocular reflex (VOR) of
      the HSCC in patients with H-BPPV. MATERIAL AND METHODS: Patients were rotated
      about the earth-vertical axis at frequencies of 0.1, 0.3, 0.5, 0.7 and 1.0 Hz
      with a maximum angular velocity of 50 degrees/s. Eye movements were recorded on a
      video imaging system using an infrared charge-coupled device (CCD) camera, and
      our new technique for analyzing the rotation vector of eye movements in three
      dimensions was used. RESULTS: In the patients with geotropic positional
      nystagmus, there were no differences in VOR gain between rotation to the affected
      and unaffected sides at frequencies of 0.1-1.0 Hz. Although no differences in VOR
      gain at frequencies of 0.3-1.0 Hz were noticed in patients with apogeotropic
      positional nystagmus, the VOR gain at 0.1 Hz was significantly smaller on
      rotation to the affected compared to the unaffected side. CONCLUSION: The results
      indicate that cupulolithiasis in the HSCC affected the dynamics of the HSCC
      ocular reflex at 0.1 Hz, but not at higher frequencies, and that canalolithiasis
      in the HSCC does not change the VOR gain of the HSCC at any frequency. It is
      suggested that cupulolithiasis causes transient impairment of HSCC function by
      means of its mechanical restriction of movements of the cupula.

PMID- 15267178
TI  - Subclassification of vestibular disorders by means of statistical analysis in
      caloric labyrinth testing.
AB  - OBJECTIVE: In the past, various attempts were made to perform a quantitative
      analysis of nystagmographic findings but their diagnostic value was limited.
      Therefore, the authors present a multivariate analysis of nystagmus findings with
      the aim of increasing the precision of diagnostic differentiation in cases of
      vestibular dysfunction. MATERIAL AND METHODS: A group of 387 patients and 40
      healthy volunteers were examined over a 14-month period using
      electronystagmography after stimulation by bithermal, bilateral irrigation of the
      labyrinth. Amplitude, slow-phase velocity, frequency and directional
      preponderance were evaluated. RESULTS: No defined normal values for caloric
      nystagmus parameters could be obtained. However, by using the Mann Whitney U-test
      and logistic regression analysis a differentiation between pathological and
      healthy findings as well as between central and peripheral vestibular disorders
      and even between distinct vestibular disease entities is possible. Using these
      methods, the nystagmus amplitude was found to be the strongest discriminating
      parameter. Therefore, sole assessment of nystagmographic findings by selective
      calculation of the nystagmus slow-phase velocity falls short of the potential
      offered by electronystagmographic registration. CONCLUSION: For daily clinical
      routine, counting nystagmus beats leads to the same diagnostic precision as the
      analysis of slow-phase velocities. In contrast, multivariate analysis of several
      nystagmus parameters can distinguish between distinct diseases with fairly high
      precision. This stepwise analysis of nystagmographic data could create the basis
      for an expert-system tool in the near future.

PMID- 15267179
TI  - Progressive bilateral sensorineural hearing loss probably induced by chronic
      cyclosporin A treatment after renal transplantation for focal glomerulosclerosis.
AB  - OBJECTIVE: The immunosuppressive agent cyclosporin A (CsA) has contributed to the
      success of organ and bone marrow transplantation. CsA-related neurotoxicity is a
      well-known occurrence. Sensorineural hearing loss (SNHL) due to initiation of CsA
      treatment is an extremely rare finding. MATERIAL AND METHODS: A 32-year-old man
      who had undergone technically uneventful cadaveric renal transplantation for
      focal glomerulosclerosis when 25 years old was evaluated as the result of a 10
      month history of bilateral hearing loss. The patient had been taking only CsA
      (150 mg twice daily) and methylprednisolone. RESULTS: Progressive bilateral SNHL
      was confirmed by an audiological examination. Eight months after dose reduction
      of CsA, pure-tone audiometry excluded progression of hearing loss. CONCLUSIONS:
      To the best of our knowledge, only rare cases of CsA-related hearing loss have
      been reported, and none after long-term CsA treatment. Audiological findings
      confirmed the cochlear origin of SNHL in our patient. The action of CsA on the
      blood-inner ear barrier has recently been demonstrated but the mechanism of
      cochlear damage is still unknown. A prospective study to determine the incidence
      of CsA-induced hearing loss has been instituted in our department.

PMID- 15267180
TI  - Low serum folate levels: a risk factor for sudden sensorineural hearing loss?
AB  - OBJECTIVE: Ischemic vascular damage of the inner ear is one of the known causes
      of sensorineural sudden hearing loss (SSHL). Folate is an emerging risk factor
      associated with an increased risk of vascular damage. The aim of this study was
      to investigate whether low serum folate levels are associated with SSHL. MATERIAL
      AND METHODS: Serum folate levels were determined in 43 patients with SSHL and in
      24 controls. RESULTS: Folate levels were found to be significantly lower in SSHL
      patients than in controls (mean difference -1.96 ng/ml; 95% CI -3.31, -0.59
      ng/ml; p = 0.006). No significant relationship between folate levels and either
      sex, age, cigarette smoking, alcohol consumption or hypertension was observed,
      while a significant relationship was found between low folate levels and high
      homocysteine (HCY) levels in all 43 patients (p < 0.01). The potential influence
      of low folate levels on hearing impairment in SSHL patients can be explained by
      the effects on HCY metabolism and the diminution of folate antioxidant capacity.
      CONCLUSION: Further studies are needed to elucidate whether low folate levels can
      be considered a risk factor for SSHL.

PMID- 15267181
TI  - Recombinant human bone morphogenetic protein-2 enhances experimental
      laryngotracheal reconstruction in rabbits.
AB  - OBJECTIVE: Bone morphogenetic protein-2 offers potential benefits for cartilage
      regeneration. We investigated the effect of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) on the regeneration of laryngeal cartilage and respiratory
      epithelium in a rabbit model. MATERIAL AND METHODS: We used a cricoid defect
      rabbit model. Twenty-four rabbits were randomly divided into four equal groups.
      Two groups were treated with 5 microg of rhBMP-2 delivered on an absorbable
      collagen sponge and the other two groups were used as controls. One group of
      treated rabbits and one group of control rabbits were euthanized 1 week after
      surgery, while the others were euthanized 4 weeks after surgery. The healing
      pattern of the laryngeal wound was evaluated by means of histomorphometry.
      RESULTS: Regeneration of both the epithelial layer and cartilage was
      significantly better in rabbits treated with rhBMP-2. Four weeks after surgery,
      the cricoid cartilage defect was completely repaired by new cartilage and new
      bone in rabbits treated with rhBMP-2. Furthermore, the lining respiratory
      epithelium healed more rapidly in treated rabbits. CONCLUSION: rhBMP-2, delivered
      via an absorbable collagen sponge, induces complete regeneration and repair of
      rabbit cricoid cartilage defects. It also induces faster relining and
      regeneration of airway epithelium than in control rabbits.

PMID- 15267182
TI  - A role for neutrophils in intermittent allergic rhinitis.
AB  - OBJECTIVE: In patients with intermittent allergic rhinitis, allergen challenge
      may induce both early- and late-phase responses. The aim of this study was to
      examine the correlation between inflammatory cells in the nasal lavage fluid and
      clinical parameters following pollen challenge. MATERIAL AND METHODS: Nasal
      lavage fluids were obtained from 29 patients with intermittent allergic rhinitis
      before and 1 and 6 h after allergen provocation, representing the control, early
      and late phases, respectively. Symptom and rhinoscopic scores were registered on
      the same occasions. Inflammatory cells were determined in the nasal fluid.
      RESULTS: The early phase was characterized by increased symptom scores,
      rhinoscopic signs of oedema and secretion and neutrophilia. In the late phase,
      symptom scores had diminished, but the signs of ongoing secretion remained. Both
      the total nasal symptom score and the secretion score correlated with the number
      of neutrophils in lavage fluids at 1 h. The eosinophil count did not increase
      during the early or late phases. CONCLUSION: A single allergen provocation
      induces an early-phase response dominated by neutrophils, with secretion being
      the only clinical sign remaining during the late phase. The increase in
      neutrophil numbers correlated with the registration of secretory symptoms. The
      presented data indicate a role for neutrophils in intermittent allergic rhinitis
      and their relation with secretory parameters makes it intriguing to speculate
      that neutrophils may function as promoters of nasal secretion.

PMID- 15267183
TI  - Actinobacillus actinomycetemcomitans suppresses rat natural killer cell activity
      in vivo.
AB  - OBJECTIVE: To examine the immune suppressive effect of Actinobacillus
      actinomycetemcomitans (Aa) on rat natural killer (NK) cell activity in vivo.
      MATERIAL AND METHODS: Sprague Dawley rats were given Aa in 2 different manners:
      (i) by mixing Aa with food at a dose of 10(8) cells/rat/day for 3 months; or (ii)
      by a single i.m. injection of live Aa at doses of 10(6) and 10(7) cells/rat/day.
      NK cell activity was measured by means of a 51Cr-release assay using YAC-1 tumor
      cells as targets. RESULTS: Rats that had been infected by Aa mixed with food
      experienced significant suppression of their NK cell activity; this reached
      approximately =50% of control values at 2 and 3 months post-Aa infection. The
      suppression in NK cell activity was related to decreases in the extent of
      conjugate formation between effectors and YAC-1 target tumor cells (51.7%) and
      the extent of lysis of target cells (75.7%). The results also showed that
      addition of an admixture of Aa-treated NK cells to the control NK cells caused
      75% and 53% decreases in activity at effector:target ratios of 25:1 and 50:1,
      respectively. In addition, a significant increase in the extent of T-suppressor
      cells (154.8% of control) was detected at 3 months post-Aa infection. In
      contrast, the single injection of live bacteria resulted in a remarkable, dose
      dependent inhibition of NK cell activity (55% and 71% at doses of 10(6) and 10(7)
      cells/rat/day, respectively) as early as 2 days post-treatment. This also
      reflected significant suppression in the effector:target conjugate formation
      ratio (52% of control). The data also revealed a 150-188% increase in the number
      of splenic lymphocytes post-Aa injection. These effects were transient and normal
      levels were re-established by the fifth day CONCLUSION: Aa treatment causes
      suppression of NK cell activity and the mode of action may be due to induction of
      T-suppressor cells or dilution of NK cells with other lymphoid cell populations.
      The degree of suppression is affected by the way in which Aa is introduced to the
      host. These results may contribute to the understanding of how Aa evades host
      defense.

PMID- 15267184
TI  - Pilot study of a novel mandibular advancement device for the control of snoring.
AB  - OBJECTIVE: Mandibular advancement devices (MADs) have been introduced as a
      conservative, non-invasive treatment for socially disturbing snoring and mild
      obstructive sleep apnea (OSA). A prospective, non-randomized pilot study was
      conducted to investigate the efficacy, feasibility, side-effects and compliance
      of Somnoguard, an immediately intraorally adaptable MAD made from thermoplastic
      material. MATERIAL AND METHODS: Twenty consecutive heavy snorers with a
      respiratory disturbance index of <20 events/h were prospectively selected. Prior
      to the adaptation of the appliance, ambulatory polygraphy was carried out without
      a MAD. After a 1-month habituation period, a polygraphic evaluation was carried
      out with the device. Treatment success was defined as a reduction in the apnea
      hypopnea index (AHI) of at least 50%. RESULTS: The results indicated a success
      rate of 65%. The AHI decreased from 8.4 +/- 2.9 events/h at baseline to 3.9 +/-
      1.8 events/h with the device (p = 0.001). At 1-month follow-up, significant
      reductions in the snoring index (p < 0.001) and the Epworth Sleepiness Scale
      (ESS) score (p = 0.036) were noted. At 6-month follow-up, similar results were
      achieved, with significant drops in the snoring index (p = 0.025) and ESS score
      (p = 0.033). CONCLUSION: We conclude that immediate intraoral adaptation of a low
      cost fabricated "one-size-only" MAD is a feasible and well-tolerated treatment
      for snoring and mild OSA. Further research is needed to evaluate this
      thermoplastic appliance as a strategy to "screen" the efficacy of MAD treatment
      in the individual patient with a less expensive appliance before constructing a
      more expensive custom-made MAD.

PMID- 15267185
TI  - Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma.
AB  - OBJECTIVE: c-myc seems to play a pivotal role in normal growth and development as
      well in cellular transformation and carcinogenesis. Overexpression of the c-myc
      oncogene has been observed in many hematopoetic and solid tumors. The role of c
      myc protein in squamous cell carcinoma of the head and neck in general and
      laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The
      aim of this study was to evaluate the relations between the level of c-myc
      protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the
      SG2M phase index (PI). MATERIAL AND METHODS: The c-myc protein level was
      evaluated immunohistochemically in tumor specimens from 50 patients with LSCC.
      The DNA index and SG2M PI were determined by means of flow cytometry. RESULTS: We
      found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was
      demonstrated to be frequent in nonmetastatic cases (p = 0.016). There was no
      association between c-myc protein level and age, primary tumor size, histological
      grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors.
      The mean value of the SG2M PI was 22.5%. Expression of c-myc protein was not
      related to SG2M PI or DNA ploidy. CONCLUSIONS: We have shown that c-myc
      oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the
      detectability of c-myc protein is associated with a lower metastatic potential.
      The c-myc oncogene is probably not as important in laryngeal cancers compared to
      other cancers. Further investigations must be performed to establish the value of
      predicting nodal metastases in LSCC.

PMID- 15267186
TI  - Immunohistochemical studies in support of a diagnosis of small cell
      neuroendocrine carcinoma of the larynx.

PMID- 15267187
TI  - Extramedullary plasmacytoma of the maxillary sinus.
AB  - Extramedullary plasmacytomas (EMPs) are localized plasma cell neoplasms that
      occur within the soft tissues; by definition they cannot occur within bone. They
      account for 1-2% of all plasma cell growths and have a great predilection for the
      upper respiratory tract, without specific manifestations. Males are more
      frequently affected during the fifth and sixth decades of life. At initial
      presentation, multiple myeloma should be excluded. We report herein the case of a
      63-year-old man with an EMP arising in the right maxillary sinus who was referred
      for surgical excision and postoperative radiotherapy and briefly review the
      clinical implications and management of this pathology.

PMID- 15267188
TI  - Successful auricle replantation via microvascular anastomosis 10 h after complete
      avulsion.
AB  - OBJECTIVE: To report a case of successful total auricle replantation 10 h after
      complete amputation. MATERIAL AND METHODS: Replantation was achieved by means of
      microvascular anastomosis and other therapies, and assisted by careful nursing.
      The patient's auricle was completely cut off with a sharp blade by an assailant,
      who retained it for 5 h. Having been retrieved, it was then preserved in ice for
      5 h. Using microscopy, an artery and vein were found at the confluences of the
      upper and middle and lower and middle parts of the amputated auricle and head
      wound, respectively An end-to-end anastomosis was performed on these vessels.
      After operation, the following treatments were used: drainage; reopening of the
      drainage channels with a needle: flushing or soaking with heparin sodium
      solution; controlling infection and coagulation; increasing blood volume:
      dilating vessels; and special nursing. RESULTS: The replanted auricle survived
      with a normal contour and a very favorable esthetic appearance. CONCLUSIONS: The
      neat, uncontaminated wound margins and the fact that the amputated auricle was
      preserved in ice, even though it had been amputated 10 h before the operation,
      were prerequisites for successful auricle replantation. The microvascular
      anastomosis technique played a very important role in the survival of the
      amputated auricle. The postoperative treatment, observation and nursing were
      difficult but vital aspects of the procedure. The establishment of an effective
      venous return was a sign of the survival of the amputated auricle.

PMID- 15267189
TI  - Pleomorphic adenoma of the lateral side of the tongue.
AB  - Pleomorphic adenoma is histopathologically the commonest tumor found in the major
      salivary glands. Pleomorphic adenoma originating from the tongue is very rare:
      only 26 cases have been reported in the world literature since 1960, only 2 of
      which originated from Ebner's gland. Herein we report the case of a 54-year-old
      female with pleomorphic adenoma of the tongue. The tumor was in contact with the
      molars. A partial glossectomy was performed with a surgical margin, as the
      preoperative pathological finding in the tissue specimen taken from the tumor was
      epithelial hyperplasia. The postoperative pathological diagnosis was pleomorphic
      adenoma with hyperplasia. It is unclear whether the teeth being in contact with
      the tumor caused tumorigenesis in this case. This case suggests that pleomorphic
      adenoma of the tongue originating from Ebner's gland should be considered in the
      differential diagnosis of lesions of the tongue.

PMID- 15267191
TI  - Squamous cell carcinoma in plantar ulcers in leprosy: a study of 11 cases.
AB  - The objectives of our study were to describe and analyse the malignancies that
      occurred in plantar ulcers of leprosy patients. The possible predisposing
      conditions, duration and extent of the spread of the tumour were also studied.
      All patients with trophic ulcer of the foot attending the urban leprosy clinic in
      our hospital from January 1998 to January 2003 were screened for change to
      malignancy. During the study period, 79 cases of plantar ulcers in leprosy were
      seen. The mean age of these cases was 39.9 years with male-to-female ratio of
      4:1. Eleven cases with plantar ulcers and malignant change were diagnosed in our
      hospital during the study period. The male-to-female ratio was 4.5:1. The mean
      age of these patients was 60.6 years. Their age ranged from 46 to 75 years. Nine
      of the cases were treated cases of borderline tuberculoid leprosy, while two had
      treated lepromatous leprosy. In our study, two distinct morphological types of
      malignant changes were seen. Histopathologically, all cases, except one, were of
      well-differentiated squamous cell carcinoma variation; one case had verrucous
      carcinoma. Though trophic ulcers are common in leprosy cases, only long-standing
      and neglected ones undergo malignancy.

PMID- 15267190
TI  - A comparative clinico-pathological study of single dose ROM in paucibacillary
      leprosy patients with 1-3 skin lesions.
AB  - A controlled clinical and histopathological study was carried out to compare the
      efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus
      minocycline 100 mg (ROM) administered as a single dose with that of standard
      WHO/MDT-PB six months' regimen with regard to resolution of lesion clinically and
      histopathologically. Skin biopsy was performed at the intake and at 6 months. The
      study subjects were 32 previously untreated, smear-negative patients, without
      nerve trunk involvement and having 1-3 skin lesions. The results were analyzed
      for mean clinical score for marked, moderate and no improvement and mean
      histopathological score was graded as active, resolving and complete resolution,
      according to granuloma fraction at the end of 6 months. Marked clinical
      improvement was seen in 25% and 12%, moderate improvement in 50% and 56% patients
      treated with ROM and standard regimens respectively. Histopathologically,
      activity was seen in 62.5% and 43.7% and resolution of granuloma in 25% and 31.2%
      in the ROM and standard regimens respectively. Both the regimens were equally
      efficacious in the reduction of clinical score and granuloma fraction. No adverse
      drug reactions or reversal reactions were seen during the study period in both
      the groups.

PMID- 15267192
TI  - Perspectives of leprosy patients on MDT services after integration of NLEP
      functions into primary health care.
AB  - Sixty-five leprosy patients residing in rural Digapahandi block of Ganjam
      district were studied during July-August 2001 in order to ascertain their
      perspectives regarding different MDT services after NLEP functions were
      integrated into primary health care (PHC) in Orissa after September 1999. They
      included 43.08% multibacillary (MB) cases and 61.92% paucibacillary (PB) cases.
      Assessment was done by personal interviews of adult patients and the parents of
      child cases after verification of their treatment cards at the sub-centre.
      Patient's knowledge regarding the availability of MDT services under PHC services
      and utilization of these services were highlighted. Influence of different socio
      demographic factors was also studied. Basing on the study results,
      recommendations were made for sustained NLEP functions through PHC in order to
      improve the utilization of MDT services, which will help in the elimination of
      leprosy.

PMID- 15267193
TI  - Evaluation of the modified leprosy elimination campaign in a high leprosy endemic
      district of Jharkhand.
AB  - An evaluation of the third Modified Leprosy Eradication Campaign (MLEC) was
      carried out in Potka block in the high endemic district of East Singhbhum,
      Jharkhand State, India, by our external evaluation team, from 29 October to 8
      November 2001. The searchers in this block detected 389 suspects during the MLEC;
      of these, 181 (46%) were examined, and 69 (38%) of them were confirmed as cases
      by the Programme staff. The evaluators examined 189 (48.5%) of the total 389
      suspects detected by the searchers, including 31 of the 69 cases confirmed by the
      Programme staff. Concordance of diagnosis of leprosy cases by the Programme staff
      and the evaluators was found to be high (90%). However, concordance of the type
      of leprosy was found to be variable (PB 38%, MB 72%, SSL 100%). Specificity and
      sensitivity of diagnosis by the Programme staff (as against those by the
      evaluators) were found to be 85.7% and 79.2% respectively. There was no case of
      re-registration. The evaluators examined 108 of the suspects detected by the
      Search Team, but not screened by the Programme staff, and diagnosed 47 cases
      (44%; PB 20, MB 9, SSL 18) from among them. The evaluators also diagnosed
      additional 30 new cases (PB 18, MB 5, SSL 7), during their visit. An assessment
      of knowledge about the disease and treatment among confirmed cases revealed that
      most of the patients did not know correctly about their disease. All the cases
      were referred by the searchers. About 45% of cases were aware of the duration for
      which they needed to take the treatment, 97% of cases showed the blister calendar
      packs and had taken the supervised dose. Availability of MDT to the patients and
      drug compliance were found to be adequate. Assessment of the impact of IEC
      activities on the awareness of leprosy among the community showed that about 50%
      of those interviewed were aware of the campaign. Most of them had information
      about the availability of leprosy drugs and knew that treatment was free. A
      majority of those aware of the disease said that they would refer suspects, if
      they come across any, to PHC centres for treatment.

PMID- 15267194
TI  - Integration of the leprosy programme into primary health care: a case study of
      perceptions of primary health care workers.
AB  - Integration of the vertical leprosy programme into the existing horizontal health
      programme poses various administrative and operational challenges to programmers.
      In order to understand the preparedness of the PHC workers for integration of
      leprosy into primary health care services, 71 PHC workers were interviewed using
      a structured interview schedule. The results showed that about 42% of the staff
      have heard of the concept of integration earlier and 90% of the PHC staff are
      willing to treat leprosy patients in the primary health care centre, but only 72%
      were in favour of integration. The reasons for favouring integration were (1)
      wider coverage with MDT, (2) frequent field visits by the worker, (3) better
      rapport with the community, (4) timely treatment and (5) cost-effectiveness.
      About 28% of the staff members did not favour integration for the reasons that
      the leprosy programme would suffer, targets cannot be met, supervision would be
      difficult, knowledge of the staff was inadequate and importance cannot be given
      to leprosy as family planning is always a priority in PHC centres. About 43% of
      the staff felt that the performance of the leprosy programme would be better
      after integration. With regard to workload, 60% of the sample felt that there
      would be increase in the workload in the field, record maintenance and
      supervision. The difficulties foreseen by the workers were grouped into 6
      categories, viz., administrative, managerial, technical, personnel, social and
      miscellaneous. It is worth noting that 91% of the staff that included all
      categories said they were not afraid of leprosy, but needed training in leprosy
      work. About 50% of the staff expected increase in salaries and promotions if
      integration took place.

PMID- 15267195
TI  - Multicentric reticulohistiocytosis misdiagnosed as lepromatous leprosy.

PMID- 15267196
TI  - Leprosy and herpes zoster; an association or dissociation?
AB  - Nerve involvement is common to the pathogenesis of both leprosy and herpes
      zoster. We report two cases of borderline leprosy in which the skin lesions
      characteristically spared the healed zoster scar. Possible mechanisms and
      relationship are discussed.

PMID- 15267197
TI  - Molluscum contagiosum-like lesions in lepromatous leprosy.

PMID- 15267198
TI  - IAL workshop on reactions in leprosy. Jamnagar, Gujarat, 11-12 January 2003.

PMID- 15267199
TI  - [Ion channels and penile erection].
AB  - Recently, more and more studies have discovered that some diseases result from
      gene defect and functional variation of ion channels, which are called ion
      passage diseases or ion channelopathies. Meanwhile, it has been found that even
      though many diseases do not fall into the category of the ion passage disease,
      some links or passages during the disease development are closely related with
      the malfunction of ion channels, and many drugs can prevent and cure these
      diseases by acting on ion channels. Therefore, the relationship between
      physiology/pathophysiology and ion channels is gradually becoming one of the hot
      topics in the current researches. The recent progress in the researches on the
      relationship between penile erection and ion channels is briefly reviewed in this
      article.

PMID- 15267200
TI  - [Changes of rat testicular germ cell apoptosis after high power microwave
      radiation].
AB  - OBJECTIVE: To study the effect of high power microwave (HPM) radiation on the
      testicular germ cell apoptosis. METHODS: One hundred and twenty-five Spraque
      Dawley rats were randomly divided into two groups, unexposed control group and
      experimental group(further divided into four subgroups: 10 mW/cm2 5 min, 10
      mW/cm2 10 min, 20 mw/cm2 5 min, and 20 mW/cm2 10 min), and then the experimental
      group was radiated with S wave band of 10 mW/cm2, 20 mW/cm2 high power microwave
      for 5 or 10 min. Testicular samples were taken at 6 h, 24 h, 48 h, 72 h and 5 d
      after radiation and separately studied. At the end of the process, testicular
      germ cell apoptosis was detected by in situ terminal deoxynucleotityl transferase
      mediated dUTP nick end labeling (TUNEL). RESULTS: The number of apoptotic cells
      of the 6 h, 24 h and 48 h experimental groups at 5 min after 10 and 20 mW/cm2
      radiation was remarkably larger than that of the controls (P < 0.01), especially
      after 10 mW/cm2 radiation, the number of the 6 h group reached the peak (161.27
      +/- 5.90) /5 convoluted seminiferous tubules. The changes in the other
      experimental groups had no significant difference compared with the controls (P >
      0.05). CONCLUSION: HPM can increase germ cell apoptosis of the rat testis, which
      is related to the time of radiation and sample acquisition. In the condition of
      the present test, 5 minutes of HPM radiation may significantly enhance testicular
      germ cell apoptosis and damage, which in turn may influence the reproductive
      function of the rats.

PMID- 15267201
TI  - [Association of single nucleotide polymorphism of vitamin D receptor gene start
      codon and the susceptibility to prostate cancer in the Han nationality in Hubei
      area].
AB  - OBJECTIVE: To investigate single nucleotide polymorphism of vitamin D receptor
      (VDR) gene start codon in the Han nationality in Hubei area and its relationship
      to the susceptibility to prostate cancer (PCa), and to study the possible
      mechanism for PCa. METHODS: The VDR genotypes were determined by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) in 80 patients with
      PCa and 96 normal male controls from the Han nationality in Hubei area, using
      endonuclease Fok I. Direct sequencing was done in part of the PCR products.
      RESULTS: The frequency distribution of Fok I alleles in this cohort all followed
      the Hardy-Weinberg equilibrium. The distribution of genotypes and alleles had no
      significant difference between PCa patients and normal male controls( P > 0.05).
      CONCLUSION: The results indicated no significant relationship between Fok I
      polymorphism of VDR gene start codon and PCa in the Han nationality in Hubei
      area.

PMID- 15267202
TI  - [Experimental study of the effect of rhTNF-alpha on human sperm mitochondrial
      function and motility in vitro].
AB  - OBJECTIVE: To study the effect of rhTNF-alpha on human sperm mitochondrial
      function and motility in vitro. METHODS: Fifty-six semen samples collected by
      masturbation were analyzed according to WHO protocols. Semen samples from 40
      healthy men were prepared using Percoll centrifugation. Sperm suspension was
      diluted to a concentration of 10 x 10(6)/ml in Ham's F10 medium. Sperm samples
      were incubated with rhTNF-alpha solution (final concentration 0.03 microg/L, 0.06
      microg/L, 0.09 microg/L and 0.27 microg/L, respectively) for 0.5 h, 1 h, 2 h, 3 h
      and 4 h at 37 degrees C in 5% CO2, and comparative studies were made with a
      control group. Ten microl sperm samples were examined with CASA technique, 250
      microl stained in the presence of 10 microg/ml Rh123 and PI, and mitochondrial
      function analyzed by flow cytometry. RESULTS: Significant differences were found
      between the experimental groups (final concentration 0.06 microg/L, 0.09 microg/L
      and 0.27 microg/L) and the control group in viability, straight line velocity,
      curvilinear velocity, average path velocity, progressive motility of human sperm
      and the number of spermatozoa with normal mitochondrial function (P < 0.01)
      except the final concentration 0.03 microg/L group (P > 0.05). Motility of human
      sperm lowered with the increase of rhTNF-alpha concentration and incubation time,
      and r values were 0.675, 0.691, 0.762, 0.693, 0.724 and 0.571, 0.594, 0.752,
      0.791, 0.816, respectively (P < 0.01). The number of spermatozoa with normal
      mitochondrial function decreased with the increased rhTNF-alpha concentration and
      incubation time, and r values were 0.615, 0.643, 0.752, 0.691, 0.754 and 0.532,
      0.567, 0.782, 0.692, 0.854, respectively (P < 0.01). CONCLUSION: rhTNF-alpha can
      reduce human sperm motility function in vitro, possibly by interfering with human
      sperm mitochondrial function.

PMID- 15267203
TI  - [Effects of experimental varicocele on mitochondria calcium and cytochrome C of
      the epididymis in adolescent rats].
AB  - OBJECTIVE: To investigate the effects of experimental varicocele on mitochondria
      calcium and cytochrome C of the epididymal cells in adolescent rats. METHODS:
      Forty male adult Wistar rats were divided into two groups randomly: varicocele
      group (VG) and sham operation group (SOG) by partial ligation or exposure of the
      left renal vein. Bilateral epididymides were removed after ten RESULTS: The
      content of mitochondria weeks. Mitochondria calcium and cytochrome C levels of
      the epididymal cells were detected. calcium decreased (P < 0.001 ) while that of
      cytochrome C increased (P < 0.05) markedly in the experimental group compared
      with SOG. CONCLUSION: Calcium dyshomeostasis and mitochondrial damage of the
      epididymal cells caused by varicocele may play an important role in leading to
      subfertility.

PMID- 15267204
TI  - [Correlation between EPS composition and elevated serum PSA in prostatitis
      patients].
AB  - OBJECTIVE: To explore the correlation between the content of lecithin mass and
      white blood cells (WBC) of the expressed prostatic secretion (EPS) and the
      concentration of serum PSA in patients with prostatitis, and to study the
      difference in serum PSA concentration between patients with bacterial prostatitis
      and those with nonbacterial prostatitis. METHODS: The serum PSA concentration in
      62 patients with prostatitis and 22 controls were measured with ELISA method. The
      correlation between the content of lecithin mass and WBC of the EPS and the
      elevation of serum PSA was analyzed. And the serum PSA concentration of bacterial
      prostatitis (9 patients) and that of nonbacterial inflammatory prostatitis (53
      patients) were compared. RESULTS: The mean concentrations of serum PSA in the
      prostatitis and the control groups were (1.79 +/- 0.68) microg/L and (0.63 +/-
      0.29) microg/L, respectively. The difference of the serum PSA concentration was
      significant between the prostatitis and the control groups (P < 0.001) as well as
      between the groups with higher and lower WBC contents in EPS (P < 0.05), but not
      between the groups with higher (27 patients) and lower (35 patients) lecithin
      mass contents in EPS (P > 0.05), nor between the groups of bacterial prostatitis
      and nonbacterial prostatitis (P > 0.05). CONCLUSION: Prostatitis may cause the
      elevation of serum PSA concentration. The elevated serum PSA correlates with the
      content of white blood cells in EPS, but not with the content of lecithin mass in
      EPS, nor with the type of prostatitis, either bacterial or nonbacterial.

PMID- 15267205
TI  - [Effect of LHRH crasis protein as vaccine on the reproductive function of male
      rats].
AB  - OBJECTIVE: To investigate the effect of Trx-LHRH, a new GnRH crasis protein, on
      antibody production and male reproductive function. METHODS: Trx-LHRH produced in
      vitro with a new crasis gene which crasised Trx gene and GnRH gene together, was
      used as vaccine, and hydroalaminum base as adjuvant, in adult SD rats. After 5
      weeks of the first treatment, the same dosage was used again to enhance the
      effect of vaccine. Antibody level was measured by ELISA, and androgen level by
      RIA. RESULTS: Trx-LHRH induced successfully the polycolonal antibody at the level
      of 1 :1 280 approximately 2 560 after 4 weeks of the first treatment, and 1 : 2
      000 after 6 weeks of the enhanced treatment. Testosterone level was reduced
      significantly (P < 0.01) by ELISA, but there was reasonable variation among
      individuals. Sperm count was also reduced by Trx-LHRH treatment. CONCLUSION: Trx
      LHRH can be used as effective vaccine to induce antibody production, and at the
      same time, restrain the function of hypothatamas-pituitary-testis axis in vivo.

PMID- 15267206
TI  - [Combined therapy for the chronic pelvic pain syndrome].
AB  - OBJECTIVE: To study the clinical diagnosis and treatment of the chronic pelvic
      pain syndrome (CPPS). METHODS: According to National Institute Health (NIH)
      classification, 165 cases of chronic prostatitis were surveyed by analysis of
      their laboratory results and clinical history. In addition, the chronic
      prostatitis symptom index (CPSI) of each patient was evaluated. All patients were
      treated for 6 to 8 weeks, type III A with antibiotics and alpha1 receptor
      inhibitor, type III B with alpha1 receptor inhibitor, diazepam diclogenatis and
      other narcotics. All cases were additionally treated by psychological and
      physical therapies. Traditional Chinese Medicine was also used in some cases.
      RESULTS: Based on the results of CPSI after 6 weeks treatment, 121 (73.3%)
      significantly improved, 26 (15.8%) slightly improved and only 18(10.9%) did not
      respond to the therapy. CONCLUSION: Combined therapy can be an effective
      treatment for the chronic pelvic pain syndrome.

PMID- 15267207
TI  - [Comparison of sperm motion parameters in pre-freeze and post-thaw semen samples
      using computer-assisted sperm analysis].
AB  - OBJECTIVE: To observe sperm motion parameters in pre-freeze and post-thaw semen
      samples using computer-assisted sperm analysis (CASA) system. METHODS: Semen
      analyses of 238 samples before freezing and after thawing were separately
      performed by Hamilton-Thorne Sperm Analyzer. RESULTS: Sperm motility in post-thaw
      samples was significantly decreased. There was significant correlation and
      difference between pre-freeze and post-thaw samples in sperm motion parameters,
      including average path velocity (VAP), straight line velocity (VSL), curvilinear
      velocity (VCL), amplitude of lateral head displacement (ALH), straightness (STR)
      and linearity (LIN), except heat cross frequency (BCF). The percentage of sperm
      movement velocity parameters (VAP, VSL and VCL) and moving pattern parameters
      (ALH) significantly decreased, while that of LIN and STR significantly increased
      in post-thaw samples. CONCLUSION: CASA system is of clinically applied value and
      is a useful tool for evaluating sperm motion parameters in pre-freeze and post
      thaw semen samples.

PMID- 15267208
TI  - [Investigation and analysis of chronic prostatitis and sexual dysfunction].
AB  - OBJECTIVE: To investigate the prevalence of sexual dysfunction in chronic
      prostatitis patients and its relation with patients' age and the course of
      disease. METHODS: Questionnaire surveys were completed by 2 000 subjects who met
      the criteria for chronic prostatitis after clinical examination and expressed
      prostatic secretion analysis. Included in the questionnaire were: (1) age,
      height, weight, occupation, course of disease and treatment received; (2) NIH
      CPSI; and (3) IIEF-5. RESULTS: The prevalence of sexual dysfunction in patients
      with chronic prostatitis was 49.0% : 26.2% of the subjects with premature
      ejaculation, 15.0% with erectile dysfunction and 7.7% with both premature
      ejaculation and erectile dysfunction. CONCLUSION: The prevalence of sexual
      dysfunction in patients with chronic prostatitis is high, which is negatively
      correlated with both the age of the patients (P < 0.001) and the course of the
      disease (P < 0.001).

PMID- 15267209
TI  - [Clinical analysis of 15 cases of Paget's disease of the scrotum].
AB  - OBJECTIVE: To study the clinicopathologic features and treatment of Paget's
      disease of the scrotum. METHODS: Fifteen cases of Paget's disease of the scrotum,
      pathologically diagnosed and successfully treated by surgery from 1987 to 2003,
      were studied retrospectively. RESULTS: Typical pathological features were
      observed in all the patients. Thirteen cases were followed up for 0. 5
      approximately 13 years, of whom 1 case relapsed within 3 years, 2 died of
      metastasis after 2 years, and 3 died of cardiovascular diseases, with no
      recurrence in the others. CONCLUSION: Early biopsy and extensive excision of the
      scrotal lesion is the first choice of treatment for Paget's disease, with good
      operative effect and satisfactory prognosis. A 2nd operation could be considered
      for patients of local relapse.

PMID- 15267210
TI  - [Investigation and analysis of the defense mechanism and domestic violence of
      male patients with somatization disorder].
AB  - OBJECTIVE: To evaluate the relationship between the psychological impediment of
      the patients with somatization disorder (SD) and domestic violence, and to
      enhance peoples recognition of this kind of patients' harmful action to others so
      as to attach more importance to the patients and to the improvement of mental
      health service of the community. METHODS: Questionnaire scoring was conducted
      among the wives of the SD group and the control group concerning domestic
      violence. It was also conducted in the SD group, the control group and the wives
      of the two groups concerning defense mechanism. RESULTS: The average score on
      demestic violence of the SD group was significantly higher than that of the
      normal control. Immature and intermediate defenses were more usual in the SD
      group than in the normal control (P < 0.01). CONCLUSION: Psychological impediment
      of SD patients is an important cause of domestic violence.

PMID- 15267211
TI  - [Studies on sex hormone-binding globulin in the prostate].
AB  - OBJECTIVE: To assay the existence of SHBG in prostatic tissue and analyze the
      effects of SHBG on the prostate and prostatic hyperplasia. METHODS: Prostate
      tissue cytosolic and nuclear fractions were obtained from 32 cases of benign
      prostatic hyperplasia (BPH), 11 cases of elderly control, and 22 cases of the
      normal young and middle-aged. SHBG in cytosol and nucleus was evaluated by two
      site immunoradiometric assay based on the 125I-labelled monoclonal antibody.
      RESULTS: The study testified the existence of SHBG in the cytosol of prostatic
      tissue. SHBG in BPH tissue [(5.11 +/- 1.37) fmol/g wet tissue] was a little more
      than that in the young and middle-aged group [(4.98 +/- 1.39) fmol/g wet tissue]
      and the elderly group [(5.06 +/- 1.27) fmol/g wet tissue], but there was no
      significance among the three groups (P > 0.05). CONCLUSION: SHBG in the prostate
      can bind and accumlate androgen, which is related to prostatic physiology and
      contributes to the etiology of BPH.

PMID- 15267212
TI  - [Apoptosis and hemodynamic changes of the penile tissue in diabetic rats].
AB  - OBJECTIVE: To compare the apoptosis and hemodynamic changes of the penile tissue
      in diabetic and healthy rats. METHODS: Sixteen chronic diabetic and 10 matched
      normal control rats were injected with a single dose of streptozotocin (STZ) 65
      mg/kg and the diabetic model established. Eight weeks later the rats were killed,
      their haemoglobin Alc( HbAlc) measured, and their penises harvested. TUNEL assay
      (in situ nick end-labeling) and flow cytometry were used to analyse the penile
      cells for apoptosis. The thickness and diameter of the arteries were measured.
      RESULTS: TUNEL showed apoptosis in the chronic diabetic rats. Flow cytometric
      analysis showed the apoptotic peak in the penile cells of the chronic diabetic
      rats when compared with the controls (P < 0.05). There was significant difference
      between the diabetic and healthy rats. Morphological analysis revealed that the
      thickness of the artery wall increased while the artery diameter decreased in the
      diabetes group compared with the controls. CONCLUSION: Diabetes can lead to
      increasing apoptosis of the penile tissue, cause a decrease in the penile artery
      diameter and the thickening of the penile artery wall.

PMID- 15267213
TI  - [Clinical evaluation of IL-1beta and TNF-alpha in prostatic secretions for
      chronic prostatitis].
AB  - OBJECTIVE: To determine the clinical significance of interleukin-1beta (IL-1beta)
      and tumor necrosis factor-alpha( TNF-alpha) in expressed prostatic
      secretions(EPS) for chronic prostatitis. METHODS: Prostatic secretions IL-1beta
      and TNF-alpha were evaluated for 34 patients with chronic prostatitis, 10 with
      asymptomatic inflammatory prostatitis, 12 with benign prostatic hyperplasia (BPH)
      and 8 health controls by enzyme-linked immunosorbent assay (ELISA). RESULTS: IL
      1beta and TNF-alpha levels in EPS in the patients of chronic prostatitis with WBC
      > or = 10/HP and asymptomatic inflammatory prostatitis were obviously higher than
      those of chronic prostatitis with WBC < 10/HP, BPH and health controls, (P < 0.05
      and P < 0.02). There was a correlation between IL-1beta and TNF-alpha (P < 0.003)
      but none between WBC and IL-1beta or TNF-alpha. CONCLUSION: Cytokines are
      frequently elevated in EPS in men of chronic prostatitis with high WBC and
      asymptomatic inflammatory prostatitis, which provides a novel means different
      from traditional methods based on WBC for the identification of men with chronic
      prostatitis.

PMID- 15267214
TI  - [Investigation of sildenafil in the treatment of prostatitis-related sexual
      dysfunction].
AB  - OBJECTIVE: To investigate the value of sildenafil in the treatment of prostatitis
      related sexual dysfunction. METHODS: Two hundred and eighty patients with chronic
      prostatitis complicated by sexual dysfunction were radomized into two groups, on
      treated with sildenafil, and the other with Quinolone. Results were analyzed by
      comparing the chronic prostatitis symptoms (CPSI score), sexual dysfunction
      symptoms (PSFI score) and anxiety symptoms (SAS score) between pre-treatment and
      post-treatment groups. RESULTS: The degree of prostatitis-related sexual
      dysfunction was not correlated with that of prostatitis symptoms. The prostatitis
      symptoms and sexual function were improved after sildenafil treatment compared
      with the control (P < 0.05), and anxiety score after treatment was significantly
      lower than the control (P < 0.05). CONCLUSION: Sildenafil not only works on
      prostatitis-related sexual dysfunction but also improves the symptoms of
      prostatitis and anxiety.

PMID- 15267215
TI  - [Sildenafil citrate for erectile dysfunction in male kidney transplant
      recipients].
AB  - OBJECTIVE: To evaluate the efficacy and safety of sildenafil citrate in man
      kidney transplant recipients with erectile dysfunction. METHODS: One hundred and
      seventy married males, aged 26 approximately 50 years, who had received kidney
      transplantations at least half a year before and whose serum creatinine was under
      133 umol/l, were selected randomly in the study. Their sexual function was
      investigated according to the International Index of Erectile Function-5 (IIEF
      5), and those with erectile dysfunction (ED) were treated with oral sildenafil
      citrate for 6 months. The efficacy was assessed by IIEF-5. RESULTS: Fifty-three
      men with ED received oral sildenafil citrate for 6 months. At the end of the
      treatment, each index in IIEF-5 increased significantly. There were no
      interactions between sildenafil and cyclosporine and there was no significant
      adverse effect of sildenafil on the graft function. CONCLUSION: Sildenafil is an
      effective and safe agent for the treatment of ED in kidney transplant recipients.

PMID- 15267216
TI  - [Advances in research on the target antigens of antisperm antibodies].
AB  - Antisperm antibodies can lead to immunological infertility. Further research on
      the target antigens of antisperm antibodies may help to discover the causal
      relationship of antisperm antibodies to infertility. This paper summarizes the
      structure and function of the six target antigens of antisperm antibodies found
      recently, so as to discover the causal relationship of the antibodies to
      infertility and provide a basis for screening a vaccine for immunological
      contraception.

PMID- 15267217
TI  - [Progress in studies of male infertility resulting from chronic prostatitis].
AB  - Chronic prostatitis (CP) is a very common disease in the male genitourinary
      system. It can result in male infertility mainly by affecting the motility or the
      function of spermatozoa and the physical and chemical nature of semen. At
      present, researches on the mechanism of male infertility resulting from CP mainly
      focus on ROS, immunological mechanism, lack of zinc and pathogenetic
      microorganism. This article briefly reviews the progress in these aspects.

PMID- 15267218
TI  - [Effects of reproductive hormones on spermatogenesis].
AB  - Spermatogenesis, a continuous course of cell proliferation and differentiation,
      depends on reproductive hormones. FSH and LH-induced T are the main hormones
      regulating spermatogensis. Intratesticular T is one of the key factors in
      maintaining spermatogenesis, while FSH is just as important for origination and
      maintenance of normal spermatogenesis. Sertoli cells are the pivot of hormonal
      regulation. Interestingly, these reproductive hormones also regulate sperm cell
      apoptosis spermatogenesis. Further studies on the hormonal regulation of
      spermatogenesis provide a base for the development of safe and recoverable
      contraceptives for males.

PMID- 15267219
TI  - Oligonucleotide-directed mutagenesis and targeted gene correction: a mechanistic
      point of view.
AB  - Within the last decade, a number of nucleic acid-based gene targeting strategies
      have been developed with the ultimate goal to cure human genetic disorders caused
      by mutations. Thus far, site-directed gene targeting is the only procedure that
      can make predefined alterations in the genome. The advantage of this approach is
      that expression of the corrected gene is regulated in the same way as a normal
      gene. In addition, targeted specific mutations can be made in the genome for
      functional analysis of proteins. Several approaches, including chimeric RNA-DNA
      oligonucleotides, short single-stranded oligonucleotides, small fragment
      homologous replacements, and triple-helix-forming oligonucleotides have been used
      for targeted modification of the genome. Due to the absence of standardized
      assays and mechanistic studies in the early developmental stages of
      oligonucleotide-directed gene alteration, it has been difficult to explain the
      large variations and discrepancies reported. Here, we evaluate the progress in
      the field, summarize the achievements in understanding the molecular mechanism,
      and outline the perspective for the future development. This review will
      emphasize the importance of reliable, sensitive and standardized assays to
      measure frequencies of gene repair and the use of these assays in mechanistic
      studies. Such studies have become critical for understanding the gene repair
      process and setting realistic expectations on the capability of this technology.
      The conventionally accepted but unproven dogmas of the mechanism of gene repair
      are challenged and alternative points of view are presented. Another important
      focus of this review is the development of general selection procedures that are
      required for practical application of this technology.

PMID- 15267220
TI  - Antisense strategies.
AB  - Antisense technology exploits oligonucleotide analogs to bind to target RNAs via
      Watson-Crick by hybridization. Once bound, the antisense agent either disables or
      induces the degradation of the target RNA. Antisense agents may also be used to
      alter splicing. Developing antisense technology involves the creation of a new
      pharmacology. The receptors, pre- and mRNAs, had never been studied before as
      sites for drug binding and action. The drugs, oligonucleotide analogs, had never
      made or tested as drugs before and no medicinal chemistry had been performed. The
      receptor binding mechanism, Watson-Crick hybridization had never been
      demonstrated as feasible to exploit from a pharmacological perspective. The post
      receptor binding events were literally unknown and unexplored. During the past
      decade or more, substantial progress has been made in developing antisense
      pharmacology. A great deal has been learned about the basic mechanisms of
      antisense, the medicinal chemistry, the pharmacological, pharmacokinetic and
      toxicological properties of antisense molecules. Antisense technology has proven
      of great value in gene functionalization and target validation. With one drug
      marketed, Vitravene, and approximately 20 antisense drugs in clinical
      development, it appears that antisense drugs may prove of value in the treatment
      of a wide range of diseases. In this review, the progress is summarized, the
      limitations of the technology discussed and the future considered.

PMID- 15267221
TI  - Ribozymes in the age of molecular therapeutics.
AB  - Ribozymes are RNA molecules capable of sequence-specific cleavage of other RNA
      molecules. Since the discovery of the first group I intron ribozyme in 1982, new
      classes of ribozymes, each with their own unique reaction, target site
      specifications, and potential applications, have been identified. These include
      hammerhead, hairpin, hepatitis delta, varkud satellite, groups I and II intron,
      and RNase P ribozymes, as well as the ribosome and spliceosome. Meanwhile,
      ribozyme engineering has enabled the in vitro selection of synthetic ribozymes
      with unique properties. This, along with advances in ribozyme delivery methods
      and expression systems, has led to an explosion in the potential therapeutic
      applications of ribozymes, whether for anti-cancer or anti-viral therapy, or for
      gene repair.

PMID- 15267222
TI  - Silencing of disease-related genes by small interfering RNAs.
AB  - In recent years a new mechanism of posttranscriptional gene silencing has been
      discovered and named RNA interference. The interference is based on mRNA
      degradation mediated by small double-stranded RNA molecules approximately 21
      nucleotides in length, the so-called short interfering or siRNAs. These molecules
      are produced from long dsRNAs by Dicer, a dsRNA-specific endonuclease, and cause
      specific degradation of their mRNA-targets by Watson-Crick base-pairing within a
      300 kD multi-enzyme complex named RISC. RNAi is highly conserved between plants
      and animals of various phyla including mammals. The high sequence-specificity of
      RNAi makes it a new, promising tool in gene-function analysis as well as in
      potential therapeutics. In this review the discovery and molecular background of
      RNAi are summarized and possible fields of application pointed out.

PMID- 15267223
TI  - Intracellular antibodies as specific reagents for functional ablation: future
      therapeutic molecules.
AB  - The use of antibodies in medicine and research depends on their specificity and
      affinity in the recogniton and binding of individual molecules. However, these
      applications are limited to the extracellular targets. Advances in antibody
      engineering has allowed the manipulation of the antibody segments containing the
      antigen-binding regions and generation of small fragments that can be stably
      expressed in cells. These entities are called intracellular antibodies or
      intrabodies and have being successfully applied, mainly in the scFv format, to
      inhibit the function of intracellular target proteins in specific cellular
      compartments. As new techniques to select and isolate intrabody fragments have
      been developed, intrabodies are beginning to be used to interfere with the
      function of a greater number of relevant disease targets. Just as monoclonal
      antibodies are opening a new era in human therapeutics, intrabodies promise a new
      prospective for antibody tools for therapy and research. Their varied mode of
      action gives intrabodies great potential in different approaches in the treatment
      of human diseases, as well as in the area of functional genomics for
      characterisation of novel gene products and subsequent validation as potential
      drug targets. While techniques for identifying functional intrabodies have
      improved, there are still many significant problems to be overcome before
      intrabodies can actually be used in treatment of diseases such as cancer, AIDS or
      neuro-degenerative disorders.

PMID- 15267224
TI  - Peptide aptamers: specific inhibitors of protein function.
AB  - In recent years, peptide aptamers have emerged as novel molecular tools that are
      useful for both basic and applied aspects of molecular medicine. Due to their
      ability to specifically bind to and inactivate a given target protein at the
      intracellular level, they provide a new experimental strategy for functional
      protein analyses, both in vitro and in vivo. In addition, by using peptide
      aptamers as "pertubagens", they can be employed for genetic analyses, in order to
      identify biochemical pathways, and their components, that are associated with the
      induction of distinct cellular phenotypes. Furthermore, peptide aptamers may be
      developed into diagnostic tools for the detection of a given target protein or
      for the generation of high-throughput protein arrays. Finally, the peptide
      aptamer technology has direct therapeutic implications. Peptide aptamers can be
      used in order to validate therapeutic targets at the intracellular level.
      Moreover, the peptide aptamer molecules themselves should possess therapeutic
      potential, both as lead structures for drug design and as a basis for the
      development of protein drugs.

PMID- 15267225
TI  - Therapeutic antibodies.
AB  - Monoclonal antibodies had the lure of drugs very much since their first
      description. The ability to bind to a predetermined chemical structure stimulated
      the imagination of drug discoverers and developers. Nevertheless it took many
      years before a drug was registered which started to make good on the promise. The
      complexity of the molecule, made up of four polypeptide chains, its large
      molecular weight, its multiple and versatile functional domains and its mouse
      origin initially were obstacles for the production and the utilisation. Also the
      selection of appropriate target structures on the surface of cells turned out be
      difficult. Many of these difficulties have been overcome. The replacement of most
      of the murine sequences with equivalent human sequences and the concomittant
      decrease in immunogenicity, and the identification of cell surface components
      which are causative and limiting in cellular transformation have made monoclonal
      antibodies valuable weapons in the fight against cancer. Multiple mechanisms of
      monoclonal antibody action are being exploited for this purpose. Antibodies can
      sequester growth factors and prevent the activation of crucial growth factor
      receptors. A monoclonal antibody directed against the vascular endothelial growth
      factor (VEGF) has been shown to be a potent neo-vascularisation inhibitor
      (bevacizumab). An antibody against the extracellular domain of the EGF receptor
      prevents the binding of the ligand to the receptor and thereby its activation
      (cetuximab). EGFR activity, however, is absolutely required for the survival and
      proliferation of certain human tumour cells. An antibody which interferes with
      the dimerisation of the ErbB2 and the ErbB3 members of the EGF receptor family
      prevents the association of a most potent signaling module (pertuxumab). The
      signals emenating from this dimer determine many phenotypic properties of e.g.
      human breast cancer cells. A monoclonal antibody also directed against ErbB2 has
      been most successful, clinically and commercially (trastuzumab). This antibody
      interferes with signals generated by the receptor and causes the arrest of the
      cell cycle in tumour cells. In addition, it recruits immune effector cells as
      cytotoxic agents. Finally, monoclonal antibody derivatives, single chain Fv
      fragments, have been used as a basis for the construction of recombinant tumour
      toxins. These molecules harness the exquisite binding specificity of the
      antibodies and combine them with the toxic principles of bacteria.

PMID- 15267226
TI  - Current clinical and preclinical photosensitizers for use in photodynamic
      therapy.

PMID- 15267227
TI  - Phosphorylcholine-carbohydrate-protein conjugates efficiently induce hapten
      specific antibodies which recognize both Streptococcus pneumoniae and Neisseria
      meningitidis: a potential multitarget vaccine against respiratory infections.
AB  - Phosphorylcholine (ChoP) is commonly expressed at the surface of pathogens of the
      respiratory tract, including Streptococcus pneumoniae and Neisseria meningitidis.
      We designed a synthetic hapten comprising ChoP and part of its native carrier
      structure in S. pneumoniae, i.e. N-acetyl-D-galactosamine (GalNAc). Protein
      conjugates of this hapten induced GalNAc-ChoP-specific antibodies which
      recognized ChoP on both S. pneumoniae and N. meningitidis. GalNAc-ChoP could
      therefore lead to the rational design of a novel multipurpose vaccine against
      respiratory infections.

PMID- 15267228
TI  - Design, synthesis, and evaluation of sugar amino acid based inhibitors of protein
      prenyl transferases PFT and PGGT-1.
AB  - Eleven analogues of the C-terminal Ca(1)a(2)X motif found in natural substrates
      of the prenyl transferases PFT and PGGT-1 were synthesized and evaluated for
      their inhibition potency and selectivity against PFT and PGGT-1. Replacement of
      the central dipeptide part a(1)a(2) by a benzylated sugar amino acid resulted in
      a good and highly selective PFT inhibitor (8, IC(50) = 250 +/- 20 nM). The methyl
      ester of 8 (13) selectively inhibited protein farnesylation in cultured cells.

PMID- 15267229
TI  - Imidazole analogues of fluoxetine, a novel class of anti-Candida agents.
AB  - Imidazole analogues of fluoxetine have been obtained by replacing the methylamino
      terminus of aminopropane chain with the imidazole ring. The newly designed
      imidazoles showed potent anti-Candida activity, superior to those of miconazole
      and other antifungal agents of clinical interest. 1-(4-Chlorophenyl)-1-(2,4
      dichlorophenoxy)-3-(1H-imidazol-1-yl)propane (16), the most active among test
      imidazoles, was about 2-fold more active and as much less cytotoxic than
      miconazole. High increase of activity was observed with methyl, nitro, fluorine,
      and chlorine (Cl > F > CH(3) > NO(2) > CF(3)).

PMID- 15267230
TI  - Novel 2-aminotetralin and 3-aminochroman derivatives as selective serotonin 5-HT7
      receptor agonists and antagonists.
AB  - The understanding of the physiological role of the G-protein coupled serotonin 5
      HT(7) receptor is largely rudimentary. Therefore, selective and potent
      pharmacological tools will add to the understanding of serotonergic effects
      mediated through this receptor. In this report, we describe two compound classes,
      chromans and tetralins, encompassing compounds with nanomolar affinity for the 5
      HT(7) receptor and with good selectivity. Within theses classes, we have
      discovered both agonists and antagonists that can be used for further
      understanding of the pharmacology of the 5-HT(7) receptor.

PMID- 15267231
TI  - Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma
      secretase.
AB  - Gamma-secretase is the second of two proteolytic enzymes responsible for the
      release of the amyloid beta-peptide implicated in the etiology of Alzheimer's
      disease. Here, we used solid-phase synthesis to generate a new series of helical
      peptides as gamma-secretase inhibitors, one of which, 11, showed an IC(50) of 140
      pM in a cell-free enzyme assay.

PMID- 15267232
TI  - Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino
      [6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors
      of glycogen synthase kinase-3.
AB  - Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin
      receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose
      similar to insulin, making GSK3 an attractive target for the treatment of type 2
      diabetes. Herein we report the discovery of a series of potent and selective GSK3
      inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II
      diabetes, and 9 and 12 have desirable PK properties.

PMID- 15267233
TI  - Spacer-arm modulated gene delivery efficacy of novel cationic glycolipids:
      design, synthesis, and in vitro transfection biology.
AB  - Design, syntheses and relative in vitro gene delivery efficacies of six novel
      cationic glycolipids 1-6 containing open-form galactosyl units in CHO, COS-1, MCF
      7 and A549 cells are described. The results of the present structure-activity
      investigation convincingly demonstrate that the in vitro gene delivery efficacies
      of galactosylated cationic glycolipids are strikingly dependent on the absence of
      a spacer-arm between the open-form galactose and the positively charged nitrogen
      atom in their headgroup region. While the cationic glycolipids 1-3 with no
      headgroup spacer unit between the positively charged nitrogen and galactose
      showed high in vitro gene transfer efficacies in all four cells (lipids 1 and 2
      with myristyl and palmityl tails, respectively, being the most efficacious),
      lipids 4-6 with five-carbon spacer units between the quaternized nitrogen and
      galactose heads were essentially transfection incompetent. The transfection
      inhibiting role of the five-carbon spacer unit in the headgroup region of the
      present novel class of cationic lipids was demonstrated by both beta
      galactosidase reporter gene expression and histochemical X-gal staining assays.
      Results of MTT assay-based cell viability measurements in representative MCF7
      cells show that cell viabilities of lipoplexes (lipid:DNA complexes) prepared
      from all the lipids 1-6 are remarkably high. Thus, possibilities of differential
      cellular cytotoxicities playing any key role behind the strikingly contrasting
      transfection properties of lipids 1-3 with no spacer and lipids 4-6 with a spacer
      unit in the headgroup regions was ruled out. Electrophoresis gel patterns in
      DNase I sensitivity assays are consistent with more free DNA (accessible to DNase
      I) being present in lipoplexes of lipids 4-6 than in lipoplexes of lipids 1-3.
      Thus, the results of our DNase I protection experiments support the notion that
      enhanced degradation of DNA associated with lipoplexes of lipids 4-6 may play an
      important role in abolishing their in vitro gene transfer efficacies.

PMID- 15267234
TI  - Contribution of ionization and lipophilicity to drug binding to albumin: a
      preliminary step toward biodistribution prediction.
AB  - Understanding the molecular mechanisms governing albumin binding is a major
      challenge in absorption-distribution-metabolism-excretion prediction. To gain
      insight into this complex field, an ultracentrifugation method to measure the
      drug fraction bound to bovine serum albumin [%B(DAB)] is presented. The second
      part of the study shows the dependence of the experimental binding parameter on
      ionization and lipophilicity descriptors (pK(a) and log D(oct)(7.4) for a series
      of 14 structurally diverse drugs. Finally, a docking strategy is used to
      rationalize the findings; the results confirm the mostly nonspecific nature of
      the interaction of albumin with neutral ligands.

PMID- 15267235
TI  - A virtual screening approach to finding novel and potent antagonists at the
      melanin-concentrating hormone 1 receptor.
AB  - Melanin-concentrating hormone (MCH) has been known to be an appetite-stimulating
      peptide for a number of years. However, it is only recently that MCH has been
      discovered to be the natural ligand for a previously "orphan" G-protein-coupled
      receptor, now designated MCH-1R. This receptor has been shown to mediate the
      effects of MCH on appetite and body weight, and consequently, drug discovery
      programs have begun to exploit this information in the search for MCH-1R
      antagonists for the treatment of obesity. In this paper, we report the rapid
      discovery of multiple, structurally distinct series of MCH-1R antagonists using a
      variety of virtual screening techniques. The most potent of these compounds (12)
      demonstrated an IC(50) value of 55 nM in the primary screen and exhibited
      antagonist properties in a functional cellular assay measuring Ca(2+) release.
      More potent compounds were identified by follow-up searches around the initial
      hit. A proposed binding mode for compound 12 in a homology model of the MCH-1R is
      also presented.

PMID- 15267236
TI  - Design, synthesis, and structure-activity relationship studies of 3,4,6
      triphenylpyran-2-ones as selective cyclooxygenase-2 inhibitors.
AB  - A group of regioisomeric 3,4,6-triphenylpyran-2-ones with a MeSO(2) pharmacophore
      at the para-position of either a C-3 phenyl or a C-4 phenyl substituent on the
      central six-membered pyran-2-one ring were prepared and evaluated in vitro for
      their abilities to inhibit the isozymes COX-1 and COX-2. Structure-activity
      relationship (SAR) data, acquired by substituent modification at the para
      position of the C-6 phenyl ring attached to the central pyranone, showed that 6
      (4-methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was the
      most potent and selective COX-2 inhibitor (COX-2 IC(50) = 0.02 microM; COX-1
      IC(50) > 100 microM) with a high COX-2 selectivity index (SI > 5000) relative to
      the reference drugs celecoxib (COX-2 IC(50) = 0.07 microM; SI = 474) and
      rofecoxib (COX-2 IC(50) = 0.50 microM; SI > 200). 6-(4-Methoxyphenyl)-3-(4
      methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was a more potent oral
      antiinflammatory agent (ID(50) = 5.6 mg/kg) than celecoxib (ID(50) = 10.8 mg/kg)
      in a carrageenan-induced rat paw edema assay. In a 4% NaCl-induced abdominal
      constriction assay, a 5 mg/kg oral dose of 12e exhibited good analgesic activity
      at different time intervals producing 37.5 and 69% inhibition of writhing at 30
      and 60 min, respectively. In contrast, the corresponding 6-(4-methoxyphenyl)-4-(4
      methanesulfonylphenyl)-3-phenylpyran-2-one regiosiomer (12o) was a less potent
      and selective COX-2 inhibitor (COX-2 IC(50) = 0.45 microM; SI = 70). A molecular
      modeling study for 12e indicated that the p-OMe substituent on the C-6 phenyl
      ring interacts with the COX-2 binding site amino acids Ile(345), Val(349),
      Leu(359), Leu(531), and Met(535) and that the OMe substituent may be responsible
      for proper orientation of the C-3 p-SO(2)Me-phenyl ring within the COX-2
      secondary pocket (Gln(192), Arg(513), and Phe(518)). These results show that the
      COX-2 selectivity and potency of 3,4,6-triphenylpyranone regioisomers can be
      modulated by appropriate placement of the p-SO(2)Me pharmacophore on either the C
      3 or C-4 phenyl moiety. In addition, electronic properties at the para-position
      of a C-6 phenyl substituent on the central pyranone ring govern COX-2 inhibitory
      potency and selectivity by controlling the orientation of the p-SO(2)Me
      pharmacophore within the COX-2 secondary pocket.

PMID- 15267237
TI  - A computational study of the binding of propidium to the peripheral anionic site
      of human acetylcholinesterase.
AB  - Combined docking and molecular dynamics (MD) simulations were carried out in
      order to investigate the binding mode of propidium at the human
      acetylcholinesterase (HuAChE) peripheral site. Two different docking protocols
      followed by cluster analyses were performed, allowing the identification of five
      high-populated and low-energy configuration families. To dynamically explore the
      behavior of the ligand at the peripheral HuAChE binding site, six complexes (five
      low-energy and one high-energy) were submitted to 2.5 ns of MD simulations. The
      representative propidium/HuAChE binding modes were chosen on the basis of both
      the docking energy score and the dynamic stability of the complexes throughout
      the MD simulations. The most stable poses of propidium at HuAChE PAS were similar
      to those experimentally determined with the murine enzyme. We therefore suggest
      that the present modeling protocol might be used in the dynamic investigation of
      the interactions of a small-molecule inhibitor with a surface-like binding site
      of a protein. Finally, because of the biological relevance of the target studied
      here, the present results can be of interest for the rational design of molecules
      potentially useful in the treatment of the Alzheimer's disease.

PMID- 15267238
TI  - Macrocyclic diacylglycerol-bis-lactones as conformationally constrained analogues
      of diacylglycerol-lactones. Interactions with protein kinase C.
AB  - A series of macrocyclic diacylglycerol (DAG)-bis-lactones were investigated as
      extreme conformationally constrained analogues of DAG-lactones in order to seek
      more potent protein kinase C (PKC) ligands with higher binding affinities and
      less lipophilicity than previous compounds. The additional constraint achieved
      the desired objective as exemplified by the macrocyclic DAG-bis-lactone 57, which
      exhibited a 6-fold higher binding affinity for PKCalpha (K(i) = 6.07 nM) than the
      corresponding nonmacrocyclic 3-alkylidene DAG-lactone 6. A structure-activity
      relationship (SAR) analysis of the macrocyclic DAG-bis-lactones demonstrated a
      parabolic relationship between activity and lipophilicity, as well as a
      predilection for the Z-alkylidene isomers as the preferred ligands. Molecular
      docking studies revealed that macrocyclic DAG-bis-lactone 57 bound to the C1b
      domain of PKCalpha exclusively in the sn-1 binding mode in contrast to DAG
      lactone 6, which showed both sn-1 and sn-2 binding modes. It is proposed that the
      high potency displayed by these macrocyclic DAG-bis-lactones results from a set
      of more favorable hydrogen bonding and hydrophobic interactions with PKCalpha as
      well as from a reduced entropy penalty due to conformational restriction.

PMID- 15267239
TI  - Interaction of noncompetitive inhibitors with an immobilized alpha3beta4
      nicotinic acetylcholine receptor investigated by affinity chromatography,
      quantitative-structure activity relationship analysis, and molecular docking.
AB  - A large number of drug substances act as noncompetitive inhibitors (NCIs) of the
      nicotinic acetylcholine receptor (nAChR) by blocking the ion flux through the
      channel. An affinity chromatography technique has been developed for
      investigating the interactions between NCIs and the alpha3beta4 subtype of
      neuronal nAChR. The data obtained from the chromatographic study were used to
      construct QSAR models of the NCI-nAChR binding with both electronic and steric
      parameters observed as important descriptors. A molecular model of the
      transmembrane domain of the alpha3beta4 subtype of nAChR was constructed and used
      to simulate the docking of a series of NCIs. A key aspect of the model was the
      discovery of the cleft produced by the incorporation of the bulky phenylalanine
      moiety into the nonpolar section of the lumen by the beta4 subunit.
      Quantitatively, the results of docking simulations modeled the experimental
      affinity data better than QSAR results. The computational approach, combined with
      the modeling of NCI-nAChR interaction by affinity chromatography, can be used to
      predict possible toxicities and adverse interactions.

PMID- 15267240
TI  - A physiological model for the estimation of the fraction dose absorbed in humans.
AB  - A physiologically based model for gastrointestinal transit and absorption in
      humans is presented. The model can be used to study the dependency of the
      fraction dose absorbed (F(abs)) of both neutral and ionizable compounds on the
      two main physicochemical input parameters (the intestinal permeability
      coefficient (P(int)) and the solubility in the intestinal fluids (S(int))) as
      well as physiological parameters such as the gastric emptying time and the
      intestinal transit time. For permeability-limited compounds, the model produces
      the established sigmoidal dependence between F(abs) and P(int). In case of
      solubility-limited absorption, the model enables calculation of the critical mass
      solubility ratio, which defines the onset of nonlinearity in the response of
      fraction absorbed to dose. In addition, an analytical equation to calculate the
      intestinal permeability coefficient based on the compound's membrane affinity and
      molecular weight was used successfully in combination with the physiologically
      based pharmacokinetic (PB-PK) model to predict the human fraction dose absorbed
      of compounds with permeability-limited absorption. Cross-validation demonstrated
      a root-mean-square prediction error of 7% for passively absorbed compounds.

PMID- 15267241
TI  - Synthesis and aromatase inhibitory activity of novel pyridine-containing
      isoflavones.
AB  - Aromatase, a cytochrome P450 hemoprotein that is responsible for estrogen
      biosynthesis by conversion of androgens into estrogens, has been an attractive
      target in the treatment of hormone-dependent breast cancer. As a result, a number
      of synthetic steroidal or nonsteroidal aromatase inhibitors have been
      successfully developed. In addition, there are several classes of natural
      products that exert potent activities in aromatase inhibition, with the
      flavonoids being most prominent. Previous studies have exploited flavone and
      flavanone scaffolds for the development of new aromatase inhibitors. In this
      paper, we describe the design, synthesis, and biological evaluation of a novel
      series of 2-(4'-pyridylmethyl)thioisoflavones as the first example of synthetic
      isoflavone-based aromatase inhibitors.

PMID- 15267242
TI  - Synthesis and biological activity of new potential agonists for the human
      adenosine A2A receptor.
AB  - New adenosine derivatives have been synthesized and tested as putative agonists
      of adenosine receptors. Compounds 2-6 derive from the introduction of several
      types of substituents (electron donating, electron withdrawing, and halogens) in
      the para-position of the phenyl ring of the parent compound 1, and compound 7
      lacks the hydroxyl group of amino alcohol 1. In radioligand binding assays using
      recombinant human A(1), A(2A), A(2B), and A(3) receptors, all compounds showed
      very low or negligible affinity for A(1) and A(2B) receptors but compounds 3, 5,
      and 7 displayed a remarkably potent affinity for the A(2A) receptor with K(i)
      values of 1-5 nM. Bromo derivative 3 displayed a selectivity A(1)/A(2A) = 62 and
      A(3)/A(2A) = 16 whereas the presence of a hydroxyl group (compound 5) improved
      the selectivity of A(1)/A(2A) and A(3)/A(2A) to 120- and 28-fold, respectively.
      When the methoxy derivative 4 lacks the hydroxyl group on the side chain
      (compound 7), the binding affinity for A(2A) is increased to 1 nM, improving
      selectivity ratios to 356- and 100-fold against A(1) and A(3), respectively. In
      Chinese hamster ovary cells transfected with human A(2A) and A(2B) receptors,
      most compounds showed a remarkable activity for the A(2A) receptor, except chloro
      derivative 2, with EC(50) values ranging from 1.4 to 8.8 nM. The compounds
      behaved as good A(2A) agonists, and all were more selective than 5'-(N
      ethylcarboxamino)adenosine (NECA), with A(2B)/A(2A) ratios of cAMP accumulation
      ranging from 48 for compound 2 to 666 for compound 7 while the corresponding
      A(2B)/A(2A) ratio for NECA was only 9. Compounds 1, 3, 5, and 7 also displayed
      higher selectivities than NECA up to 100-fold in isolated aortas of rat and
      guinea pig. In guinea pig tracheal rings precontracted by carbachol, compounds 2
      and 4 were more potent than adenosine (100-fold) and NECA (10-fold), whereas
      compounds 1 and 7 displayed similar effects to NECA. Pretreatment of the tracheal
      rings with A(2), A(2A), and A(2B) receptor antagonists 3,7-dimethyl-l
      propargylxanthine, 8-(3-chlorostyryl)caffeine, and alloxazine produced a marked
      inhibition of the tracheal relaxations induced by compounds 1, 2, and 4, but none
      of the compounds showed selectivity toward any of the adenosine receptors.

PMID- 15267243
TI  - Discovery of the pyrrolo[2,1-f][1,2,4]triazine nucleus as a new kinase inhibitor
      template.
AB  - The pyrrolo[2,1-f][1,2,4]triazine nucleus was identified as a novel kinase
      inhibitor template which effectively mimics the well-known quinazoline kinase
      inhibitor scaffold. Attachment of a 4-((3-chloro-4-fluorophenyl)amino)
      substituent to the template provided potent biochemical inhibitors of the
      tyrosine kinase activity of EGFR, as well as inhibition of cellular proliferation
      of the human colon tumor cell line DiFi. Attachment of a 4-((3-hydroxy-4
      methylphenyl)amino) substituent provided potent inhibitors of VEGFR-2 which also
      showed effects on the VEGF-dependent proliferation of human umbilical vein
      endothelial cells. Biological activity was maintained with substitution at
      positions 5 or 6, but not 7, suggesting that the former positions are promising
      sites for introducing side chains which modulate physicochemical properties.
      Preliminary inhibition studies with varying ATP concentrations suggest that, like
      the quinazoline-based kinase inhibitors, the pyrrolotriazine-based inhibitors
      bind in the ATP pocket.

PMID- 15267244
TI  - Probing the activity differences of simple and complex brominated aryl compounds
      against 15-soybean, 15-human, and 12-human lipoxygenase.
AB  - Lipoxygenases (LO) have been implicated in asthma, immune disorders, and various
      cancers. As a consequence of these broad biological implications, there is great
      interest in understanding the effects of naturally occurring and environmental
      contaminants against its activity. On the basis of our earlier studies indicating
      that polybrominated diphenol ethers are potent inhibitors to mammalian 15-LO, we
      expanded our structure-activity study to include marine-derived brominated phenol
      ethers (including a newly discovered tribrominated diphenyl ether), dioxins, and
      bastadins, as well as the synthetic brominated fire retardants, brominated
      bisphenol A (BBPA), and polybrominated diphenyl ethers (PBDEs). We report herein
      the effects of 21 simple and complex organobromine compounds against human
      platelet 12-LO, human reticulocyte 15-LO, and soybean 15-LO-1.

PMID- 15267245
TI  - Direct influence of C-terminally substituted amino acids in the Dmt-Tic
      pharmacophore on delta-opioid receptor selectivity and antagonism.
AB  - A series of 17 analogues were developed on the basis of the general formula H-Dmt
      Tic-NH-CH(R)-R' (denotes chirality; R = charged, neutral, or aromatic functional
      group; R' = -OH or -NH(2)). These compounds were designed to test the following
      hypothesis: the physicochemical properties of third-residue substitutions C
      terminal to Tic in the Dmt-Tic pharmacophore modify delta-opioid receptor
      selectivity and delta-opioid receptor antagonism through enhanced interactions
      with the mu-opioid receptor. The data substantiate the following conclusions: (i)
      all compounds had high receptor affinity [K(i)(delta) = 0.034-1.1 nM], while that
      for the mu-opioid receptor fluctuated by orders of magnitude [K(i)(mu) = 15.1
      3966 nM]; (ii) delta-opioid receptor selectivity [K(i)(mu)/K(i)(delta)] declined
      1000-fold from 22,600 to 21; (iii) a C-terminal carboxyl group enhanced
      selectivity but only as a consequence of the specific residue; (iv) amidated,
      positive charged residues [Lys-NH(2) (6), Arg-NH(2) (7)], and a negatively
      charged aromatic residue [Trp-OH (11)] enhanced mu-opioid affinity [K(i)(mu) =
      17.0, 15.1, and 15.7 nM, respectively], while Gly-NH(2) (8), Ser-NH(2) (10), and
      His-OH (12) were nearly one-tenth as active; and (v) D-isomers exhibited mixed
      effects on mu-opioid receptor affinity (2' << 3' < 4' < 1' < 5') and decreased
      delta-selectivity in D-Asp-NH(2) (1') and D-Lys(Ac)-OH (5'). The analogues
      exhibited delta-opioid receptor antagonism (pA(2) = 6.9-10.07) and weak mu-opioid
      receptor agonism (IC(50) > 1 microM) except H-Dmt-Tic-Glu-NH(2) (3), which was a
      partial delta-opioid receptor agonist (IC(50) = 2.5 nM). Thus, these C-terminally
      extended analogues indicated that an amino acid residue containing a single
      charge, amino or guanidino functionality, or aromatic group substantially altered
      the delta-opioid receptor activity profile (selectivity and antagonism) of the
      Dmt-Tic pharmacophore, which suggests that the C-terminal constituent plays a
      major role in determining opioid receptor activity as an "address domain".

PMID- 15267247
TI  - Phenylguanidines as selective nonpeptide melanocortin-5 receptor antagonists.
AB  - A series of phenylguanidine analogues represented by 10, 12, and 21 were
      synthesized and found to have high binding affinities for the human melanocortin
      5 receptor. Their binding affinities for three other melanocortin receptor
      subtypes, MC1, MC3, and MC4, were low. Selected compounds were also tested for
      their functional activity and exhibited inhibition of alpha-MSH-stimulated cAMP
      production in cells expressing the human MC5 receptor. Compound 10 had a K(i)
      value of 2.1 nM in the binding assay and an IC(50) of 72 nM in the functional
      assay. Some analogues such as 13 from this series possessed weak agonist activity
      at the human MC4 receptor.

PMID- 15267246
TI  - Anti-AIDS agents. 60. Substituted 3'R,4'R-di-O-(-)-camphanoyl-2',2'
      dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents.
AB  - Synthesis of positional isomers is a commonly used technique in drug design.
      Accordingly, based on prior SAR studies of 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis
      khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone
      derivatives of 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3
      f]chromone (DCP, 4) were designed and synthesized. Together with 1 and 4-methyl
      DCK (2), all newly synthesized DCP analogues (4-21) were screened for anti-HIV-1
      activity against a non-drug-resistant strain in H9 lymphocytes and a multiple
      reverse transcriptase (RT) inhibitor-resistant strain in the MT4 cell line.
      Several DCP analogues (4, 5, 7, 8, 13, and 17) exhibited extremely high anti-HIV
      activity in the non-drug-resistant strain assay, with EC(50) values ranging from
      0.00032 to 0.0057 microM and remarkable therapeutic indexes (TI) ranging from 5.6
      x 10(3) to 1.16 x 10(5), which were similar to those of 2 (EC(50) 0.0059 microM,
      TI > 6.6 x 10(3)) and better than those of 1 (EC(50) 0.049 microM, TI > 328).
      Even more promisingly, some DCP analogues also showed activity against a multi-RT
      inhibitor-resistant strain, HIV-1 RTMDR1, whereas most DCK analogues did not. The
      most significant compound was 8, with an EC(50) value of 0.06 microM and TI of
      718 against the multi-RT inhibitor-resistant HIV-1 strain. Compounds 9 and 10
      also showed good activity with an EC(50) value of 0.14 microM, and TIs of 272 and
      >111, respectively. 2-Ethyl DCP (8) exhibited the best anti-HIV activity in both
      assays. Further development of 8-related compounds as clinical trial candidates
      is warranted.

PMID- 15267248
TI  - Design, synthesis, and biological activity of potent and selective inhibitors of
      blood coagulation factor Xa.
AB  - Factor Xa (FXa) has materialized as a key enzyme for the intervention of the
      blood coagulation cascade and for the development of new antithrombotic agents.
      FXa is the lone enzyme responsible for the production of thrombin and therefore
      is an attractive target for the control of thrombus formation. We have designed
      and synthesized a unique series of quinoxalinone FXa inhibitors. This series
      resulted in 3-[4-[5-((2S,6R)-2,6-dimethylpiperidin-1-yl)pentyl]-3-oxo-3,4
      dihydroquinoxolin-2-yl]benzamidine (35) with 0.83 nM activity against FXa and
      excellent selectivity over similar serine proteases. An X-ray crystal structure
      of compound 35 bound to trypsin along with molecular modeling has led to a
      predicted binding conformation of compound 35 in FXa. Compound 35 has also been
      proven to be efficacious in vivo in both the rabbit veno-venous shunt and dog
      electrolytic injury models. In addition, it was shown that compound 35 did not
      significantly increase bleeding times in a rabbit model except at the highest
      doses and plasma concentrations were elevated in a dose dependent manner
      following a bolus dose and continuous intravenous infusion.

PMID- 15267249
TI  - Toward the development of a synthetic group a streptococcal vaccine of high
      purity and broad protective coverage.
AB  - Using native chemical ligation, we synthesized a group A streptococcal (GAS)
      vaccine that contained three different GAS M protein peptide epitopes in a
      chemically well-characterized construct in high purity. Two of the peptide
      epitopes represented variable amino terminal serotype determinants, and the third
      represented a carboxyl terminal conserved region determinant of the GAS M
      protein. We also synthesized a lipid core peptide (LCP) construct containing the
      same three peptides. Upon immunization of mice, the non-LCP construct only
      elicited antibody responses to all three epitopes with the use of adjuvant. The
      LCP construct, however, elicited excellent antibody responses to all three
      epitopes without the need for any additional adjuvant or carrier. We have
      synthesized the LCP synthetic vaccine system with good reproducibility.

PMID- 15267250
TI  - Structural studies on bioactive compounds. 39. Biological consequences of the
      structural modification of DHFR-inhibitory 2,4-diamino-6-(4-substituted
      benzylamino-3-nitrophenyl)-6-ethylpyrimidines ('benzoprims').
AB  - Benzimidazole-N-oxide modifications of potent lipophilic dihydrofolate reductase
      (DHFR) inhibitors (e.g., methylbenzoprim 1 and dichlorobenzoprim 2) have been
      prepared by base-promoted cyclization of the nitrophenylbenzylamino groups to
      explore the possibility that abrogation of DHFR-inhibitory activity might reveal
      clues to an alternative anti-ras mechanism. Examples of the new series had only
      low growth inhibitory activities (GI(50) generally >50 microM) against colon
      HCT116 and lung HT29 cell lines but, unlike methylbenzoprim, this activity was
      unaffected by hypoxanthine/thymidine rescue.

PMID- 15267252
TI  - Normal modes and frequencies from covariances in molecular dynamics or Monte
      Carlo simulations.
AB  - We propose a simple method to obtain normal modes (NMs) and their characteristic
      frequencies from molecular dynamics or Monte Carlo simulations at any
      temperature. The resulting NM are consistent with the vibrational density of
      states (DOS) (every feature of the DOS can be attributed to one or few NMs). At
      low temperatures they coincide with the ones obtained from the Hessian matrix. We
      define the NMs (rho(i)) by imposing the condition that their velocities be
      uncorrelated to each other: rho(i)(t)rho(j)(t) proportional, variant delta(ij),
      where denotes time average and delta(ij) is Kronecker's delta. With this
      definition the modes are the eigenvectors of the matrix K(ij)(v)=1/2<square root
      of (m(i)m(j))v(i)v(j)> [i, j=1,...,3N (N being the number of atoms); m are masses
      and v atomic velocities]. The eigenvalues of K(ij)(v), lambda(i)(v), represent
      the kinetic energy in each NM. The ratio between the eigenvalues (lambda(i)(v))
      and those obtained using positions (lambda(i)(r)), accelerations (lambda(i)(a))
      in K(ij)(v) instead of velocities are a very good approximation to the mode
      frequencies: 2pinu(i) approximately (lambda(i)(v)/lambda(i)(x))((1/2))
      approximately (lambda(i)(a)/lambda(i)(x))((1/4)). We demonstrate the new method
      using with two cases: an isolated water molecule and a crystalline polymer.

PMID- 15267253
TI  - Transition from atomic to molecular adsorption of oxygen on tungsten monomer
      anion.
AB  - Using vibrationally resolved ultraviolet photoelectron spectroscopy, we studied
      oxygen adsorption on W monomer anions. Three oxygen atoms are atomically bound in
      a WO3- compound, whereas in WO4- the fourth oxygen atom is attached to the
      oxygen, forming a di-oxygen species, implying that atom to molecule transition of
      O2 takes place when the number of oxygen atoms attached to a W monomer anion
      exceeds three. Our results indicate that molecular adsorption of oxygen is
      preferred on electron-deficient metals, showing that the driving force of the
      atom to molecule transition for the chemisorption of diatomic molecules can be
      the variations of electronic structures of metal hosts.

PMID- 15267254
TI  - Dynamical multiple-time stepping methods for overcoming resonance instabilities.
AB  - Current molecular dynamics simulations of biomolecules using multiple time steps
      to update the slowly changing force are hampered by instabilities beginning at
      time steps near the half period of the fastest vibrating mode. These "resonance"
      instabilities have became a critical barrier preventing the long time simulation
      of biomolecular dynamics. Attempts to tame these instabilities by altering the
      slowly changing force and efforts to damp them out by Langevin dynamics do not
      address the fundamental cause of these instabilities. In this work, we trace the
      instability to the nonanalytic character of the underlying spectrum and show that
      a correct splitting of the Hamiltonian, which renders the spectrum analytic,
      restores stability. The resulting Hamiltonian dictates that in addition to
      updating the momentum due to the slowly changing force, one must also update the
      position with a modified mass. Thus multiple-time stepping must be done
      dynamically.

PMID- 15267255
TI  - A diffusion quantum Monte Carlo study of geometries and harmonic frequencies of
      molecules.
AB  - This article describes an approach in determination of equilibrium geometries and
      harmonic frequencies of molecules by the Ornstein-Uhlenbeck diffusion quantum
      Monte Carlo method based on the floating spherical Gaussians. In conjunction with
      a projected and renormalized Hellmann-Feynman gradient and an electronic energy
      at variational Monte Carlo and diffusion quantum Monte Carlo, respectively, the
      quasi-Newton algorithm implemented with the Broyden-Fletcher-Goldfarb-Shanno
      updated Hessian was used to find the optimized molecular geometry. We applied
      this approach to N2 and H2O molecules. The geometry and harmonic frequencies
      calculated were consistent with some sophisticated ab initio calculated values
      within reasonable statistical uncertainty.

PMID- 15267256
TI  - Density functional theory with alternative spin densities: application to
      magnetic systems with localized spins.
AB  - A new method to improve the excess spin density obtained from unrestricted
      Hartree-Fock wave functions in terms of natural orbitals is proposed. Using this
      modified excess spin density to evaluate the correlation energy by means of
      density functionals leads to large improvements in the computed magnetic coupling
      constants of several materials without need to modify the exchange contribution.
      This is important because it reconciles the density functional theory description
      with the one provided by multi-determinant wave functions. Using the present
      approach, the leading contribution to the magnetic coupling constant arises from
      electron correlation effects. The performance of the new method is illustrated on
      various materials including high-critical-temperature superconductors parent
      compounds.

PMID- 15267257
TI  - Long-time and unitary properties of semiclassical initial value representations.
AB  - We numerically compare the semiclassical "frozen Gaussian" Herman-Kluk propagator
      [Chem. Phys. 91, 27 (1984)] and the "thawed Gaussian" propagator put forward
      recently by Baranger et al. [J. Phys. A 34, 7227 (2001)] by studying the quantum
      dynamics in some nonlinear one-dimensional potentials. The reasons for the lack
      of long-time accuracy and norm conservation in the latter method are uncovered.
      We amend the thawed Gaussian propagator with a global harmonic approximation for
      the stability of the trajectories and demonstrate that this revised propagator is
      a true alternative to the Herman-Kluk propagator with similar accuracy.

PMID- 15267258
TI  - Improved convergence in block copolymer self-consistent field theory by Anderson
      mixing.
AB  - A modification to real space polymeric self-consistent field theory algorithms
      that greatly improves the convergence properties is presented. The method is
      based on Anderson mixing [D. G. Anderson, J. Assoc. Comput. Mach. 12, 547
      (1965)], and each iteration computed takes negligibly longer to perform than with
      other methods, but the number of iterations required to reach a high accuracy
      solution is greatly reduced. No a priori knowledge of possible phases is required
      to apply this method. We apply our approach to a standard diblock copolymer melt,
      and demonstrate iteration reductions of more than a factor of 5 in some cases.

PMID- 15267259
TI  - Fluid-like behavior of a one-dimensional granular gas.
AB  - We study the properties of a one-dimensional (1D) granular gas consisting of N
      hard rods on a line of length L (with periodic boundary conditions). The
      particles collide inelastically and are fluidized by a heat bath at temperature
      Tb and viscosity gamma. The analysis is supported by molecular dynamics
      simulations. The average properties of the system are first discussed, focusing
      on the relations between granular temperature Tg=mv2, kinetic pressure, and
      density rho=N/L. Thereafter, we consider the fluctuations around the average
      behavior obtaining a slightly non-Gaussian behavior of the velocity distributions
      and a spatially correlated velocity field; the density field displays clustering:
      this is reflected in the structure factor which has a peak in the k approximately
      0 region suggesting an analogy between inelastic hard core interactions and an
      effective attractive potential. Finally, we study the transport properties,
      showing the typical subdiffusive behavior of 1D stochastically driven systems,
      i.e., </x(t)-x(0)/2> approximately Dt(1/2), where D for the inelastic fluid is
      larger than the elastic case. This is directly related to the peak of the
      structure factor at small wave vectors.

PMID- 15267260
TI  - The well-tempered auxiliary-field Monte Carlo.
AB  - The auxiliary-field Monte Carlo (AFMC) is a method for computing ground-state and
      excited-state energies and other properties of electrons in molecules. For a
      given basis set, AFMC is an approximation to full-configuration interaction and
      the accuracy is determined predominantly by an inverse temperature "beta"
      parameter. A considerable amount of the dynamical correlation energy is recovered
      even at small values of beta. Yet, nondynamical correlation energy is
      inefficiently treated by AFMC. This is because the statistical error grows with
      beta, warranting increasing amount of Monte Carlo sampling. A recently introduced
      multi-determinant variant of AFMC is studied, and the method can be tuned by
      balancing the sizes of the determinantal space and the beta-parameter with
      respect to a predefined target accuracy. The well-tempered AFMC is considerably
      more efficient than a naive AFMC. As a welcome "byproduct" low lying excitation
      energies of the molecule are supplied as well. We demonstrate the principles on
      dissociating hydrogen molecule and torsion of ethylene where we calculate the
      (unoptimized) torsional barrier and the vertical singlet-triplet splitting.

PMID- 15267261
TI  - Exact effective Hamiltonian theory. II. Polynomial expansion of matrix functions
      and entangled unitary exponential operators.
AB  - Our recent exact effective Hamiltonian theory (EEHT) for exact analysis of
      nuclear magnetic resonance (NMR) experiments relied on a novel entanglement of
      unitary exponential operators via finite expansion of the logarithmic mapping
      function. In the present study, we introduce simple alternant quotient
      expressions for the coefficients of the polynomial matrix expansion of these
      entangled operators. These expressions facilitate an extension of our previous
      closed solution to the Baker-Campbell-Hausdorff problem for SU(N) systems from N<
      or =4 to any N, and thereby the potential application of EEHT to more complex NMR
      spin systems. Similarity matrix transformations of the EEHT expansion are used to
      develop alternant quotient expressions, which are fully general and prove useful
      for evaluation of any smooth matrix function. The general applicability of these
      expressions is demonstrated by several examples with relevance for NMR
      spectroscopy. The specific form of the alternant quotients is also used to
      demonstrate the fundamentally important equivalence of Sylvester's theorem (also
      known as the spectral theorem) and the EEHT expansion.

PMID- 15267262
TI  - Fock space multireference coupled cluster calculations based on an underlying
      bivariational self-consistent field on Auger and shape resonances.
AB  - The Fock space multireference coupled cluster based on an underlying
      bivariational self-consistent field is applied to the problem of computing
      complex energy associated with Auger and shape resonances in e-atom scattering.
      It is concluded that the Fock space multireference coupled cluster based on a
      bivariational self-consistent field provides a useful and practical approach to
      calculation of resonance parameters. Numerical results are presented for the 2P
      shape resonance of Mg and Auger 1 s(-1) hole of Be.

PMID- 15267263
TI  - Towards an accurate representation of electrostatics in classical force fields:
      efficient implementation of multipolar interactions in biomolecular simulations.
AB  - The accurate simulation of biologically active macromolecules faces serious
      limitations that originate in the treatment of electrostatics in the empirical
      force fields. The current use of "partial charges" is a significant source of
      errors, since these vary widely with different conformations. By contrast, the
      molecular electrostatic potential (MEP) obtained through the use of a distributed
      multipole moment description, has been shown to converge to the quantum MEP
      outside the van der Waals surface, when higher order multipoles are used.
      However, in spite of the considerable improvement to the representation of the
      electronic cloud, higher order multipoles are not part of current classical
      biomolecular force fields due to the excessive computational cost. In this paper
      we present an efficient formalism for the treatment of higher order multipoles in
      Cartesian tensor formalism. The Ewald "direct sum" is evaluated through a
      McMurchie-Davidson formalism [L. McMurchie and E. Davidson, J. Comput. Phys. 26,
      218 (1978)]. The "reciprocal sum" has been implemented in three different ways:
      using an Ewald scheme, a particle mesh Ewald (PME) method, and a multigrid-based
      approach. We find that even though the use of the McMurchie-Davidson formalism
      considerably reduces the cost of the calculation with respect to the standard
      matrix implementation of multipole interactions, the calculation in direct space
      remains expensive. When most of the calculation is moved to reciprocal space via
      the PME method, the cost of a calculation where all multipolar interactions (up
      to hexadecapole-hexadecapole) are included is only about 8.5 times more expensive
      than a regular AMBER 7 [D. A. Pearlman et al., Comput. Phys. Commun. 91, 1
      (1995)] implementation with only charge-charge interactions. The multigrid
      implementation is slower but shows very promising results for parallelization. It
      provides a natural way to interface with continuous, Gaussian-based
      electrostatics in the future. It is hoped that this new formalism will facilitate
      the systematic implementation of higher order multipoles in classical
      biomolecular force fields.

PMID- 15267264
TI  - Radiative transition probabilities, lifetimes and dipole moments for the
      vibrational levels of the X1Sigma+ ground state of 39K85Rb.
AB  - Using a potential energy curve (based primarily on the RKR potential of Amiot and
      Verges [J. Chem. Phys. 112, 7068 (2000)]) and a dipole moment function (based
      primarily on ab initio calculations of Park et al. [Chem. Phys. 257, 135
      (2000)]), we have calculated radiative transition probabilities (Einstein A
      coefficients), radiative lifetimes, and dipole moment expectation values
      involving all vibrational levels (for several rotational quantum numbers) of the
      X1Sigma+ ground state of 39K85Rb. We observe that the radiative lifetimes of
      vibrationally excited levels, in particular, are approximately 10(3)-10(6)
      seconds, far too long to be significant in most ultracold experiments involving
      39K85Rb or its isotopomers. Comparison with other molecules (LiH and HF) suggests
      that simple scaling (A approximately mu2nu3 approximately tau(-1)) will predict
      similarly long lifetimes for many other heteronuclear molecules, e.g., RbCs.

PMID- 15267265
TI  - Theoretical study of the He-HF+ complex. I. The two asymptotically degenerate
      ground state potential energy surfaces.
AB  - Two three-dimensional potential energy surfaces (PESs) are reported for the
      cationic complex He-HF+; they are degenerate for linear geometries of the complex
      and correlate with the doubly degenerate X2Pi ground state of the HF+monomer. The
      PESs are computed from the interaction energies of the neutral dimer and the
      ionization potentials of the He-HF complex and the HF molecule. Ionization
      potentials are obtained from the outer valence Green's function (OVGF) method,
      while the energies of the neutral species are computed by means of the single and
      double coupled-cluster method with perturbative triples [CCSD(T)]. For
      comparison, interaction energies of the ionic complex were computed also by the
      use of the partially spin-restricted variant of the CCSD(T) method. After
      asymptotic scaling of the OVGF results, good agreement is found between the two
      methods. A single global minimum is found in the PES, for the linear He-HF+
      geometry. The well depth and equilibrium separation are 2.240 A and 1631.3 cm(
      1), respectively, at an HF+ bond length r=1.0012 A, in rather good agreement with
      results of Schmelz and Rosmus [Chem. Phys. Lett. 220, 117 (1994)]. The well depth
      depends much more strongly on the internuclear H-F separation than in the neutral
      He-HF complex and the global minimum in a full three-dimensional PES occurs at
      r=1.0273 A.

PMID- 15267266
TI  - Theoretical study of the He-HF+ complex. II. Rovibronic states from coupled
      diabatic potential energy surfaces.
AB  - The bound rovibronic levels of the He-HF+ complex were calculated for total
      angular momentum J=1/2, 3/2, 5/2, 7/2, and 9/2 with the use of ab initio diabatic
      intermolecular potentials presented in Paper I and the inclusion of spin-orbit
      coupling. The character of the rovibronic states was interpreted by a series of
      calculations with the intermolecular distance R fixed at values ranging from 1.5
      to 8.5 A and by analysis of the wave functions. In this analysis we used
      approximate angular momentum quantum numbers defined with respect to a dimer body
      fixed (BF) frame with its z axis parallel to the intermolecular vector R and with
      respect to a molecule-fixed (MF) frame with its z axis parallel to the HF+ bond.
      The linear equilibrium geometry makes the He-HF+ complex a Renner-Teller system.
      We found both sets of quantum numbers, BF and MF, useful to understand the
      characteristics of the Renner-Teller effect in this system. In addition to the
      properties of a "normal" semirigid molecule Renner-Teller system it shows typical
      features caused by large-amplitude internal (bending) motion. We also present
      spectroscopic data: stretch and bend frequencies, spin-orbit splittings, parity
      splittings, and rotational constants.

PMID- 15267267
TI  - Imaging the pair-correlated excitation function: The F+CH4-->HF(v')+CH3(nu=0)
      reaction.
AB  - The velocity map ion imaging technique was applied to measure the reaction
      excitation function for the first time. It was found that the "raw" excitation
      function was significantly distorted by the density-to-flux transformation of the
      title reaction. Through a systematic investigation, possible reasons for such a
      dramatic effect are outlined. In addition, the state-resolved, pair-correlated
      excitation functions and branching ratios are presented. Effects of imperfect
      time slicing in the time-sliced velocity imaging technique in general are also
      discussed.

PMID- 15267268
TI  - Dissociation of multiply ionized isocyanic acid through electron impact.
AB  - The dissociation of singly to triply ionized isocyanic acid (HNCO) has been
      investigated by two- and three-dimensional covariance mapping techniques through
      electron impact ionization at an electron energy of 200 eV. The absolute cross
      sections for the various dissociation channels of up to triply ionized HNCO have
      been measured. The HNCO dications dissociate mostly into ion pairs, while the
      HNCO trications dissociate mostly into ion triples, both through all the possible
      bond cleavages and charge allocations. Some major ion-pair dissociation channels
      of HNCO2+ are supposed to be sequential dissociation through initial charge
      separation. The metastable decay traces caused by HNCO(2+)-->H(+)+NCO+ and
      HNCO(+)-->HCO(+)+N have been observed on the covariance map.

PMID- 15267269
TI  - Low temperature pressure broadening of NH3 by D2.
AB  - We report experimentally measured cross sections for pressure broadening of
      ammonia inversion transitions by J=0, ortho-D2 at temperatures of 18-40 K. These
      measurements were made in a quasiequilibrium cell using the collisional cooling
      technique. Cross sections for broadening of the metastable (J,K)=(1, 1), (2, 2)
      and (3, 3) inversion transitions ranged from 67.5 A2 for (1, 1) at 20.0 K to
      100.1 A2 for (3, 3) at 25.0 K. The J=0, ortho-D2 cross sections were found to be
      consistently larger than previously measured cross sections for low temperature
      broadening of NH3 by both He and H2.

PMID- 15267270
TI  - The dynamics of conformational isomerization in flexible biomolecules. I. Hole
      filling spectroscopy of N-acetyl tryptophan methyl amide and N-acetyl tryptophan
      amide.
AB  - The conformational isomerization dynamics of N-acetyl tryptophan methyl amide
      (NATMA) and N-acetyl tryptophan amide (NATA) have been studied using the methods
      of IR-UV hole-filling spectroscopy (HFS) and IR-induced population transfer
      spectroscopy (IR-PTS), which were developed for this purpose. Single
      conformations of these molecules were selectively excited in well-defined NH
      stretch fundamentals. This excess energy was used to drive conformational
      isomerization. By carrying out the infrared excitation early in a supersonic
      expansion, the excited molecules were recooled into their zero-point levels,
      partially refilling the hole created in the ground state population of one of the
      conformers, and creating gains in population in other conformers. These changes
      in population were detected using laser-induced fluorescence downstream in the
      expansion. In HFS, the IR wavelength is fixed and the UV laser tuned in order to
      determine where the population went following selective infrared excitation. In
      IR-PTS, the UV is fixed to monitor the population of a given conformation, and
      the IR is tuned to record the IR-induced changes in the population of the
      monitored conformer. Besides demonstrating the capability of the experiment to
      change the downstream conformational population distribution, the IR-PTS scans
      were used to extract two quantitative results: (i) The fractional populations of
      the conformers in the absence of the infrared, and (ii) the isomerization quantum
      yields for each of the six unique amide NH stretch fundamentals (three conformers
      each with two amide groups). The method for obtaining quantum yields is described
      in detail. In both NATMA and NATA, the quantum yields show modest conformational
      specificity, but only a hint of vibrational mode specificity. The prospects for
      the hole-filling technique for providing insight into energy flow in large
      molecules are discussed, leaving a more detailed theoretical modeling to the
      adjoining paper [Evans et al. J. Chem. Phys. 120, 148 (2004)].

PMID- 15267271
TI  - The dynamics of conformational isomerization in flexible biomolecules. II.
      Simulating isomerizations in a supersonic free jet with master equation dynamics.
AB  - Infrared-induced conformational isomerization of N-acetyl-tryptophan methyl amide
      is studied theoretically using a microcanonical Rice-Ramsperger-Kassel-Marcus
      description of the rates on potential energy surfaces calculated using the AMBER
      and OPLS-AA force fields. The results are compared with the experimental data
      from Dian et al. in the preceding paper [J. Chem. Phys. 120, 133 (2004)]. An
      exhaustive search of the potential energy surfaces locates all minima and
      transition states on these surfaces. A simple model is proposed for the
      vibrational cooling, and an appropriate cooling rate is chosen as the standard
      conditions for the master equation simulations by comparison with experiment. The
      two potential energy surfaces differ in the relative energies of minima and the
      heights of key transition states, leading to differences in the dominant pathways
      and rates of conformational isomerization. The predicted quantum yields depend
      sensitively on the cooling rate, varying from the slow cooling limit in which
      equilibrium populations are achieved to the fast quenching limit in which
      conformational isomerization is shut off. The excitation energy is varied from 5
      to 20 kcal mol(-1). At the lowest energies, isomerization is completely quenched,
      while at the highest energies, equilibrium conditions are achieved. In between
      these extremes, the quantum yields are sensitive to the excitation energy, and
      can be used to locate the rate-limiting barriers to isomerization.

PMID- 15267272
TI  - Combined electronic and nuclear dynamics in a simple model system. II.
      Spectroscopic transitions.
AB  - We investigate the correlated electronic and nuclear motion in a model system as
      proposed by Shin and Metiu [J. Chem. Phys. 102, 9285 (1995)]. The quantum
      dynamics is studied during laser induced electronic transitions. Here, the
      influence of nonadiabatic coupling on the absorption spectrum is investigated and
      the Franck-Condon principle is illustrated in terms of the temporal changes of
      electronic and nuclear densities. In the case of intense field excitation,
      multiphoton processes become important, and electronic as well as vibrational
      wave packets are prepared.

PMID- 15267273
TI  - Molecular dynamic simulations of atom-cluster collision processes.
AB  - Monomer-cluster collisions of Lennard-Jones argon atoms have been studied using
      molecular dynamics simulation for target cluster sizes of 2, 3, 4, 5, 10, and 20
      atoms. Capture probability of monomers by clusters and the lifetimes of the
      resulting clusters have been calculated as a function of impact parameter and the
      total energy of the target cluster. Cluster lifetime is further integrated over
      all impact parameters to obtain the average lifetime for each cluster size and
      energy. The average lifetime of the smallest aggregates is shown to be short
      compared to the collision time between monomers and clusters unless the vapor is
      highly supersaturated. The formation probability of a new cluster decreases
      steeply if a minimum lifetime is required for the cluster.

PMID- 15267274
TI  - Many-body interaction in glycine-(water)3 complex using density functional theory
      method.
AB  - Various configurations were investigated to find the most stable structures of
      glycine-(water)3 complex. Five different optimized conformers of glycine-(water)3
      complex are obtained from density functional theory calculations using 6-311++G*
      basis set. Relaxation energy and many body interaction energies (two, three, and
      four body) are also calculated for these conformers. Out of the five conformers,
      the most stable conformer has the BSSE corrected total energy -513.917 967 7
      Hartree and binding energy -27.28 Kcal/mol. It has been found that the relaxation
      energies, two body energies and three body energies have significant contribution
      to the total binding energy whereas four body energies are very small. The
      chemical hardness and chemical potential also confirmed the stability of the
      conformer having lowest total energy.

PMID- 15267275
TI  - Equation-of-motion spin-flip coupled-cluster model with single and double
      substitutions: Theory and application to cyclobutadiene.
AB  - While the equation-of-motion coupled-cluster (EOM-CC) method is capable of
      describing certain multiconfigurational wave functions within a single-reference
      framework (e.g., open-shell type excited states, doublet radicals, etc.), it may
      fail in cases of more extensive degeneracy, e.g., bond breaking and polyradicals.
      This work presents an extension of the EOM-CC approach to these chemically
      important situations. In our approach, target multiconfigurational wave functions
      are described as spin-flipping excitations from the high-spin reference state.
      This enables a balanced treatment of nearly degenerate electronic configurations
      present in the target low-spin wave functions. The relations between the
      traditional spin-conserving EOM models and the EOM spin-flip method is discussed.
      The presentation of the formalism emphasizes the variational properties of the
      theory and shows that the killer condition is rigorously satisfied in single
      reference EOM-CC theories. The capabilities and advantages of the new approach
      are demonstrated by its application to cyclobutadiene.

PMID- 15267276
TI  - On-the-fly ab initio trajectory calculations of the dynamics of Cl atom reactions
      with methane, ethane and methanol.
AB  - The dynamics of Cl atom reactions with methane, ethane, and methanol have been
      studied by calculation of quasi-classical trajectories, with computation of
      potential energies and gradients only at the geometries through which the
      trajectories pass. Trajectories were started from the transition state, with 2
      kcal mol(-1) of energy given to the mode with an imaginary frequency
      (representing the reaction coordinate at the transition state) and inclusion of
      zero-point energy in some or all of the remaining vibrational modes. The
      trajectories were propagated as far as separated products, with the majority of
      potential energy calculations performed at the HF/6-31G level of theory. The
      rotational quantum state population distributions of the HCl products from the
      reactions of Cl atoms with methane, ethane and methanol peaked at J'=1, 2, and 6,
      respectively. The calculations thereby exhibit somewhat greater rotational
      excitation than is found experimentally, but correctly describe the trend of
      increasing HCl product rotation for the three respective reactions. In agreement
      with previous observations, only 4% of the energy available to the products of
      the reaction of Cl atoms with methane was channeled into CH3 radical internal
      energy, and 1% into HCl rotation, with 92% ending up as translational energy. For
      the reaction of Cl atoms with ethane and with methanol, the corresponding values
      for radical internal energy, HCl rotation and product translation are 21, 3, and
      78%, and 46, 13, and 42%, respectively. For the latter two reactions, the radical
      internal energy is mostly accounted for by rotational motion. The clear increase
      in rotational excitation of the HCl products from the Cl atom reaction with
      methanol is explained in terms of a dipole-dipole interaction between the
      departing polar fragments. A smaller set of more computationally expensive
      trajectory calculations using potentials and gradients from the MP2/6-311G(d,p)
      level of theory were performed for reactions of Cl atoms with methanol, and give
      results in better agreement with experimentally measured HCl rotational
      excitation, consistent with the model of dipole-induced product rotation because
      the MP2/6-311G(d,p) calculations give smaller dipole moments for both products
      than the HF/6-31G calculations. The calculated angles between the rotational
      angular momentum vectors and recoil velocities of the radical peak sharply at 90
      degrees for the reactions of Cl atoms with ethane and methanol, but exhibit a
      much broader distribution for reaction with methane.

PMID- 15267277
TI  - Proton transfer dynamics of the reaction H3O(+)(NH3,H2O)NH4+ studied using the
      crossed molecular beam technique.
AB  - The proton transfer reaction of H3O+ and NH3 was studied using the crossed
      molecular beam technique at relative energies of 0.41, 0.81, and 1.27 eV. At all
      three energies, the center-of-mass flux distribution of the product ion NH4+
      exhibits sharply asymmetry, and the maximum is close to the velocity and
      direction of the precursor ammonia beam. The reaction transforms almost all of
      the 1.69 eV exothermicity into internal excitation of the products at all three
      collision energies. At the lowest collision energy of 0.41 eV, nearly 77% of the
      total energy appears in NH4+ internal excitation. However, almost 100% of the
      incremental translational energy in the two higher-energy experiments appears in
      the product translational energy. Such an observation provides a classic example
      of the "induced repulsive energy release" mechanism that is expected to be
      operative on the highly skewed potential energy surfaces characteristic of the
      heavy+light-heavy mass combination. These results indicate that the proton
      transfer proceeds through a direct reaction mechanism; a Rice-Ramsperger-Kassel
      Marcus theory calculation shows that the lifetime of the intermediate complex
      [NH3-H-H2O]+ is about 100 fs. Proton transfer occurs early on the reaction
      coordinate, when the incipient N-H bond is extended, and results in highly
      vibrationally excited NH4+ products, with excitation primarily in N-H stretching
      modes.

PMID- 15267278
TI  - Analysis of hot D2O emission using spectroscopically determined potentials.
AB  - Fourier transform emission spectra of D2O vapor were recorded at a temperature of
      1500 degrees C in the wavenumber range 380-1880 cm(-1). 15 346 lines were
      measured, of which the majority were identified as belonging to D2O. The spectrum
      was analyzed using variational nuclear motion calculations based on
      spectroscopically determined potential-energy surfaces. Initial assignments were
      made using a potential surface obtained by fitting a high accuracy ab initio
      potential. The new assignments were used to refine the potential surface,
      resulting in additional assignments. A total of 6400 D2O transitions were
      assigned and 2144 new D2O energy levels were obtained. Transitions involving the
      4nu2 and 5nu2 bending states, with band origins of 4589.30 (+/-0.02) and 5679.6
      (+/-0.1) cm(-1), respectively, were assigned for the first time.

PMID- 15267279
TI  - Electron attachment to PSCl3.
AB  - Electron attachment to PSCl3 was studied in 133-Pa pressure of helium gas at
      temperatures from 298-550 K. Measurements of rate constants and branching
      fractions were made in a flowing-afterglow Langmuir-probe (FALP) apparatus. These
      experiments yielded an electron attachment rate constant of 5.1 x 10(-8) cm3 s(
      1) that was found not to change significantly in the 298-550 K temperature range.
      This rate constant represents an attachment efficiency of about 14%. Attachment
      in 133 Pa of He gas yielded only the dissociative ion products PSCl2- and Cl-.
      The FALP data suggest that there is an activation energy of about 17 meV for
      production of PSCl2-. Attachment to PSCl3 was also studied at high pressure (9-93
      kPa) of N2 in an ion mobility mass spectrometer, at 298 K. In contrast to the low
      pressure data, the parent anion product channel (PSCl3-) was observed (along with
      the dissociative channels), and increased in importance with N2 pressure.
      Gaussian-3 (G3) calculations were carried out for PSCl3 and PSCl2 neutrals and
      anions to aid in interpretation of the experimental results. The calculations
      indicate that the electron affinity EA(PSCl2) is slightly smaller than EA(Cl),
      which may account for the observed branching fractions for PSCl2- and Cl- in the
      low-pressure experiments. A natural population analysis was performed to obtain
      the charges associated with each atom in the molecules in order to estimate how
      the attached electron is distributed. Comparison is made between the present
      study of electron attachment to PSCl3 and our earlier work on attachment to
      POCl3, and G3 calculations are reported here for neutral and anionic POCl2 and
      POCl3. In contrast to PSCl2, the calculations imply that EA(POCl2) is slightly
      greater than EA(Cl). For both PSCl3 and POCl3, the calculations show that the
      dissociative electron attachment process is close to thermoneutral.

PMID- 15267280
TI  - Experimental and theoretical study of line mixing in NH3 spectra. II. Effect of
      the perturber in infrared parallel bands.
AB  - In a previous paper [J. Chem. Phys. 116, 7544 (2002) (Paper I)] a model, based on
      the energy corrected sudden approximation, was proposed for the construction of
      the line-mixing relaxation matrix. It was successfully tested by comparisons with
      measured infrared spectra of ammonia-helium mixtures. The present paper extends
      this preliminary study by considering mixtures of NH3 with H2 and Ar.
      Measurements have been made at room temperature in the regions of the nu2 and nu1
      bands for pressures up to several hundred atmospheres. As in Paper I, the
      relaxation operator is constructed, within the impact approximation, using the
      ECS approximation. The data required are dynamical factors (which can be
      predicted from the NH3-X potential energy surface) and a scaling length (adjusted
      using line broadening data). Comparisons between measured and calculated
      absorptions demonstrate the quality of the model which satisfactory corrects for
      the large deviations with respect to the purely Lorentzian behavior. Line-mixing
      effects for NH3-Ar and NH3-H2 are qualitatively similar to those observed for NH3
      He but quantitative differences exist, particularly when intra- and interbranch
      couplings are considered. Finally, the proposed model leads to very satisfactory
      results in the wings of both the purely rotational and nu2 bands of NH3 diluted
      in H2, opening promising perspectives for the remote sensing study of planetary
      atmospheres.

PMID- 15267281
TI  - Quantitative spectroscopic and theoretical study of the optical absorption
      spectra of H2O, HOD, and D2O in the 125-145 nm region.
AB  - The room temperature absorption spectra of water and its isotopomers D2O and HOD
      have been determined in absolute cross section units in the 125 to 145 nm
      wavelength region using synchrotron radiation. The experimental results for these
      B band spectra are compared with results from quantum mechanical calculations
      using accurate diabatic ab initio potentials. A Monte Carlo sampling over the
      initial rotational states of the molecules is applied in order to calculate the
      cross sections at a temperature of 300 K. The overall rotation of the water
      molecule is treated exactly. Both for the experimental and for the theoretical
      spectrum an analysis is made in terms of a component attributed to rapid direct
      dissociation processes and a component attributed to longer-lived resonances. The
      agreement between the results from experiment and theory is excellent for H2O and
      D2O. In the case of HOD in the results of theory two more resonances are found at
      low energy. It is demonstrated that the width of the resonances of 0.04 eV is the
      result of overlapping and somewhat narrower resonances in the spectra of
      molecules differing in rotational ground state.

PMID- 15267282
TI  - Degradation of inter-atomic bonds during structural phase change in intermediate
      Ni-clusters (Ni39-Ni49).
AB  - Results based on a symmetry- and spin-unrestricted tight-binding molecular
      dynamics study are presented for the ground-state geometries of intermediate
      Ni(n), n in [39,49], clusters. A structural phase change is found to take place
      around n=43 during which a structural transition from fcc/hcp structure to
      icosahedral one is observed. This is in good agreement with recent experimental
      findings. This structural transition is found to be associated with a degradation
      of the inter-atomic bond energy which indicates that the inter-atomic bond does
      not only depend on the coordination number of each atom but also on its point
      group symmetry.

PMID- 15267283
TI  - Impurity-stimulated heterogeneous nucleation of supercooled H2 clusters.
AB  - The sizes and mass spectra of large (N=1900-13,700 molecules) cold (approximately
      3.1 K) H2 clusters have been measured after scattering from CO molecules. Cluster
      size measurements after between 2 and 8 collisions indicate that 7% of the H2
      molecules are evaporated. This loss agrees with calculations for the number of H2
      molecules evaporated by the heat released in the transition from an initial
      liquid state to a final solid state. Even though heterogeneous nucleation is
      initiated after only a few collisions with CO molecules, the mass spectra show
      that additional captured CO molecules coagulate to form large CO clusters with up
      to n=11 molecules, suggesting that the outer layer is sufficiently liquidlike to
      facilitate mobility of the CO molecules. Since the calculated H2 cluster
      temperature (approximately 3.1 K) is below the superfluid transition temperature
      predicted for pH2 with density between 40% and 80% of the triple-point density, a
      shell-like region of low density near the cluster surface can be expected to be
      superfluid.

PMID- 15267284
TI  - Accurate ab initio pair potentials between helium and the heavier group 2
      elements.
AB  - Interactions between the heavier Group 2 metals (Ca, Sr, and Ba) and helium were
      studied using the well-tempered model core potential method. Accurate pair
      potentials, calculated at the coupled-cluster level of theory with very large
      basis sets, were used in bound state calculations. Three bound rovibrational
      states were found for each complex. The pair-potential parameters were used to
      predict how each of the metal atoms would be solvated by a helium nanodroplet.
      The Ca atom is not fully solvated by the droplet and the interaction between the
      helium and the metal decreases from Ca to Ba. This agrees with the experimental
      observation that the spectra of these atoms in a nanodroplet are intermediate
      between the spectra of the free atoms and the spectra in liquid helium.

PMID- 15267285
TI  - Accurate double many-body expansion potential energy surface for triplet H3+. II.
      The upper adiabatic sheet (2(3)A').
AB  - We report on a global potential energy hypersurface for the upper sheet of the
      lowest triplet state of H3+. The analytic representation is based on the double
      many-body expansion theory. The ab initio data points, calculated with a large cc
      pV5Z basis, are represented with a root mean square deviation of only 5.54 cm(-1)
      in the energy region below the H(+)+2H(2S) dissociation threshold. The quasi
      bound vibronic states supported by this surface have also been calculated.

PMID- 15267286
TI  - Two-dimensional Raman and infrared vibrational spectroscopy for a harmonic
      oscillator system nonlinearly coupled with a colored noise bath.
AB  - Multidimensional vibrational response functions of a harmonic oscillator are
      reconsidered by assuming nonlinear system-bath couplings. In addition to a
      standard linear-linear (LL) system-bath interaction, we consider a square-linear
      (SL) interaction. The LL interaction causes the vibrational energy relaxation,
      while the SL interaction is mainly responsible for the vibrational phase
      relaxation. The dynamics of the relevant system are investigated by the numerical
      integration of the Gaussian-Markovian Fokker-Planck equation under the condition
      of strong couplings with a colored noise bath, where the conventional
      perturbative approach cannot be applied. The response functions for the fifth
      order nonresonant Raman and the third-order infrared (or equivalently the second
      order infrared and the seventh-order nonresonant Raman) spectra are calculated
      under the various combinations of the LL and the SL coupling strengths.
      Calculated two-dimensional response functions demonstrate that those
      spectroscopic techniques are very sensitive to the mechanism of the system-bath
      couplings and the correlation time of the bath fluctuation. We discuss the
      primary optical transition pathways involved to elucidate the corresponding
      spectroscopic features and to relate them to the microscopic sources of the
      vibrational nonlinearity induced by the system-bath interactions. Optical
      pathways for the fifth-order Raman spectroscopies from an "anisotropic" medium
      were newly found in this study, which were not predicted by the weak system-bath
      coupling theory or the standard Brownian harmonic oscillator model.

PMID- 15267287
TI  - Kinetics of phase transformation on a Bethe lattice.
AB  - A kinetic Ising model is applied to the description of phase transformations on a
      Bethe lattice. A closed set of kinetic equations for a model with the
      coordination number q=3 is obtained using a procedure developed in a previous
      paper. For T close to Tc(T>Tc), where Tc is the phase transition temperature, and
      zero external field (absence of supersaturation), the rate of phase
      transformation (RPT) for small deviations from equilibrium is independent of time
      and tends to zero as (T-Tc). At T=Tc, the RPT depends on time and for large times
      behaves as t(-1). For T<Tc, we examine the transformation from the initial state
      with almost all spins "down" to the state with almost all spin "up" after the
      external field jumped from Bi<0 to Bf>0. The role of different mechanisms
      responsible for growth (decay), splitting (coagulation), and creation
      (annihilation) of clusters are examined separately. In all cases there is a
      critical value Bc of the external field, such that the phase transformation takes
      place only for Bf>Bc. This result is also obtained from a more simple
      consideration involving spherical-like clusters on a Bethe lattice. The
      characteristic time tR at which the polarization becomes larger than zero
      diverges as (Bf-Bc)(-b) for Bf-->Bc with b=0.47. The RPT has a rapid growth near
      tR and remains constant for t>tR. The average cluster size (number of spins in a
      cluster) exhibits a rapid unrestricted growth at a time td approximately tR which
      indicates the creation of infinite clusters. The only exception to the latter
      behavior occurs when the kinetics is dominated by cluster growth and decay
      processes. In this case, the average cluster size remains finite during the
      transformation process. In contrast to the classical theory, the present approach
      does not separate the processes of creation of clusters of critical size
      (nucleation) and of their growth, both being accounted for by the kinetic
      equations employed.

PMID- 15267288
TI  - Binary homogeneous nucleation in water-succinic acid and water-glutaric acid
      systems.
AB  - Binary homogeneous nucleation of water-succinic acid and water-glutaric acid
      systems have been investigated. The numerical approach was based on the classical
      nucleation theory. Usually, nucleation is discussed in terms of kinetics, but the
      thermodynamics involved is undoubtedly equally important. In this paper we
      studied the above mentioned binary systems giving a quantitative insight into the
      nucleation process and a detailed consideration of the thermodynamics involved.
      Both diacids in study are in solid state at room temperature. They behave in
      environment according to their liquid state properties because of the absence of
      crystalline lattice energies, and therefore their subcooled liquid state
      thermodynamics have to be considered. The lack of consistent thermodynamic data
      for pure organic components and their aqueous solutions represent a high source
      of uncertainty. However, the present simulations indicate that in atmospheric
      conditions these binary systems will not form new particles.

PMID- 15267289
TI  - Vibrational coherence of I2 in solid Kr.
AB  - Time-resolved coherent anti-Stokes Raman scattering, with a resolution of 20 fs,
      is used to prepare a broadband vibrational superposition on the ground electronic
      state of I2 isolated in solid Kr. The coherent evolution of a packet consisting
      of nu=1-6 is monitored for as many as 1000 periods, allowing a precise analysis
      of the material response and radiation coherence. The molecular vibrations are
      characterized by omega(e)=211.330(2) cm(-1), omega(e)x(e)=0.6523(6) cm(-1),
      omega(e)y(e)=2.9(1) x 10(-3) cm(-1); the dephasing rates at 32 K range from 110
      ps for nu=1 to 34 ps for nu=6, with nu dependence: gamma(nu)=8.5 x 10(-3)+4.9 x
      10(-4)nu2+2.1 x 10(-6)nu4 ps(-1). The signal amplitude is also modulated at
      omega(q)=41.56(3) cm(-1); which can be interpreted as coupling between the
      molecule and a local mode. The surprising implication is that this resonant local
      mode is decoupled from the lattice phonons, a finding that cannot be rationalized
      based on a normal-mode analysis.

PMID- 15267290
TI  - Towards an assessment of the accuracy of density functional theory for first
      principles simulations of water.
AB  - A series of Car-Parrinello (CP) molecular dynamics simulations of water are
      presented, aimed at assessing the accuracy of density functional theory in
      describing the structural and dynamical properties of water at ambient
      conditions. We found negligible differences in structural properties obtained
      using the Perdew-Burke-Ernzerhof or the Becke-Lee-Yang-Parr exchange and
      correlation energy functionals; we also found that size effects, although not
      fully negligible when using 32 molecule cells, are rather small. In addition, we
      identified a wide range of values of the fictitious electronic mass (micro)
      entering the CP Lagrangian for which the electronic ground state is accurately
      described, yielding trajectories and average properties that are independent of
      the value chosen. However, care must be exercised not to carry out simulations
      outside this range, where structural properties may artificially depend on micro.
      In the case of an accurate description of the electronic ground state, and in the
      absence of proton quantum effects, we obtained an oxygen-oxygen correlation
      function that is overstructured compared to experiment, and a diffusion
      coefficient which is approximately ten times smaller.

PMID- 15267291
TI  - Ab initio centroid path integral molecular dynamics: application to vibrational
      dynamics of diatomic molecular systems.
AB  - An ab initio centroid molecular dynamics (CMD) method is developed by combining
      the CMD method with the ab initio molecular orbital method. The ab initio CMD
      method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For
      the H2 molecule, the temperature dependence of the peak frequency of the
      vibrational spectral density is investigated. The results are compared with those
      obtained by the ab initio classical molecular dynamics method and exact quantum
      mechanical treatment. It is shown that the vibrational frequency obtained from
      the ab initio CMD approaches the exact first excitation frequency as the
      temperature lowers. For the HF molecule, the position autocorrelation function is
      also analyzed in detail. The present CMD method is shown to well reproduce the
      exact quantum result for the information on the vibrational properties of the
      system.

PMID- 15267292
TI  - Theoretical analysis of the relation between H2 dissociation and reflection on Pd
      surfaces.
AB  - We study the scattering of H2 (v=0, J=0) molecules by the Pd(110) surface using
      classical trajectory methods. We show that the dissociative adsorption
      probability barely depends on incidence angle (total energy scaling) up to an
      impact energy of 200 meV. This is the consequence of a "loss of memory" of the
      initial incidence angle, mostly due to dynamic trapping, which also reflects
      itself in a cosinelike angular distribution of reflected molecules. Consequently,
      a cosinelike distribution can be the result of a subpicosecond process that
      involves neither energy dissipation to the surface nor transient thermal
      accommodation.

PMID- 15267293
TI  - Reverse Monte Carlo simulations, Raman scattering, and thermal studies of an
      amorphous Ge30Se70 alloy produced by mechanical alloying.
AB  - The short- and intermediate-range orders of an amorphous Ge30Se70 alloy produced
      by mechanical alloying were studied by reverse Monte Carlo simulations of its x
      ray total structure factor, Raman scattering, and differential scanning
      calorimetry. The simulations were used to compute the G(Ge-Ge) (RMC)(r), G(Ge-Se)
      (RMC)(r), and G(Se-Se) (RMC)(r) partial distribution functions and the S(Ge-Ge)
      (RMC)(K), S(Ge-Se) (RMC)(K), and S(Se-Se) (RMC)(K) partial structure factors. We
      calculated the coordination numbers and interatomic distances for the first and
      second neighbors and the bond-angle distribution functions Theta(ijl)(cos theta).
      The data obtained indicate that the structure of the alloy has important
      differences when compared to alloys prepared by other techniques. There are a
      high number of Se-Se pairs in the first shell, and some of the tetrahedral units
      formed seemed to be connected by Se-Se bridges.

PMID- 15267294
TI  - Electronic interactions in a branched chromophore investigated by nonlinear
      optical and time-resolved spectroscopy.
AB  - The third order nonlinear optical properties of a trimer branched chromophore
      system and its linear molecule analog are investigated. Two-photon absorption and
      degenerate four wave mixing measurements were carried out on both systems. An
      enhancement in the nonlinear optical effect is observed for the branched trimer
      molecule in comparison to the linear chromophore system. Ultrafast time-resolved
      measurements were carried out to probe the excited state dynamics in the branched
      structures. The time-resolved measurements suggest that the two important
      processes affecting the nonlinear optical properties in the trimer system, charge
      transfer stabilization and initial electronic delocalization, occur on two
      different time scales.

PMID- 15267295
TI  - The size of neutral free clusters as manifested in the relative bulk-to-surface
      intensity in core level photoelectron spectroscopy.
AB  - A new approach for obtaining an estimate of the effective size of the free
      neutral clusters is proposed. The approach relies on an experimental measure of
      the surface and interior or "bulk" cluster atoms provided by the x-ray
      photoelectron spectroscopy and on a model for the attenuation of photoelectrons
      ejected from the bulk of the cluster as the result of the ionizing irradiation.
      The experimental part gives the ratio of the electron signal from the bulk
      cluster atoms to that from the cluster surface atoms for a wide range of cluster
      sizes and electron kinetic energies. The attenuated response of the bulk atoms is
      modeled using an exponential law with the cluster size and kinetic-energy
      dependent electron escape depth as parameters. For the experimental size range,
      model-based calculations for Ar, Kr, and Xe clusters are presented. The cluster
      size estimates obtained from comparison of the model calculations and
      experimental results agree well with those determined from the parameters of the
      cluster creation process. The combination of experiment and modeling also makes
      it possible to estimate the effective escape depth for electron propagation in
      free clusters. For Ar, Kr, and Xe clusters of varying mean size, absolute
      determination of the surface and bulk electron binding energies of the core
      levels used in the experiments has also been made.

PMID- 15267296
TI  - Electromagnetic fields around silver nanoparticles and dimers.
AB  - We use the discrete dipole approximation to investigate the electromagnetic
      fields induced by optical excitation of localized surface plasmon resonances of
      silver nanoparticles, including monomers and dimers, with emphasis on what size,
      shape, and arrangement leads to the largest local electric field (E-field)
      enhancement near the particle surfaces. The results are used to determine what
      conditions are most favorable for producing enhancements large enough to observe
      single molecule surface enhanced Raman spectroscopy. Most of the calculations
      refer to triangular prisms, which exhibit distinct dipole and quadrupole
      resonances that can easily be controlled by varying particle size. In addition,
      for the dimer calculations we study the influence of dimer separation and
      orientation, especially for dimers that are separated by a few nanometers. We
      find that the largest /E/2 values for dimers are about a factor of 10 larger than
      those for all the monomers examined. For all particles and particle orientations,
      the plasmon resonances which lead to the largest E-fields are those with the
      longest wavelength dipolar excitation. The spacing of the particles in the dimer
      plays a crucial role, and we find that the spacing needed to achieve a given /E/2
      is proportional to nanoparticle size for particles below 100 nm in size. Particle
      shape and curvature are of lesser importance, with a head to tail configuration
      of two triangles giving enhanced fields comparable to head to head, or rounded
      head to tail. The largest /E/2 values we have calculated for spacings of 2 nm or
      more is approximately 10(5).

PMID- 15267297
TI  - Boundary effects of molecular diffusion in nanoporous materials: a pulsed field
      gradient nuclear magnetic resonance study.
AB  - The boundary conditions of intraparticle diffusion in nanoporous materials may be
      chosen to approach the limiting cases of either absorbing or reflecting
      boundaries, depending on the host-guest system under study and the temperature of
      measurement. Pulsed field gradient nuclear magnetic resonance is applied to
      monitor molecular diffusion of n-hexane and of an n-hexane-tetrafluoromethane
      mixture adsorbed in zeolite crystallites of type NaX under either of these
      limiting conditions. Taking advantage of the thus-established peculiarities of
      mass transfer at the interface between the zeolite bulk phase and the surrounding
      atmosphere, three independent routes for probing the crystal size are compared.
      These techniques are based on (i) the measurement of the effective diffusivity
      under complete confinement, (ii) the application of the so-called NMR tracer
      desorption technique, and (iii) an analysis of the time dependence of the
      effective diffusivity in the short-time limit where, by an appropriate variation
      of the adsorbate and the measuring conditions, the limiting cases of reflecting
      and adsorbing boundaries could be considered. All these techniques are found to
      yield coinciding results, which are in excellent agreement with the crystal sizes
      determined by microscopy.

PMID- 15267298
TI  - Static light scattering from microgel particles: model of variable dielectric
      permittivity.
AB  - We perform static light scattering experiments on a dilute suspension of microgel
      particles and model the resultant form factors Pq by assuming an exponentially
      decaying dielectric permittivity. The result is that Pq is a Lorentzian function
      of the scattering wavevector q for length scales greater than the particle size;
      the width approximately corresponding to twice the particle radius. This simple
      model reasonably accounts for scattered light from both swollen and shrunken
      microgel phases.

PMID- 15267299
TI  - Improved thermal stability of Langmuir-Blodgett films through an intermolecular
      hydrogen bond and metal complex.
AB  - Langmuir-Blodgett (LB) films of N-octadecanoyl-L-alanine and its silver and zinc
      complexes have been investigated by variable-temperature Fourier transform
      infrared transmission spectroscopy. The thermal stability of LB films is improved
      through an intermolecular hydrogen bond and metal complex. The intermolecular
      hydrogen-bonding interaction between hydrophilic head groups in the same
      monolayers and the metal complex between one head group and another in the
      neighboring monolayers considerably increase the interaction between the
      corresponding hydrophobic alkyl chains. It is shown that the transformation of
      the triclinic subcell packing of the molecules in the LB films prior to and after
      the silver complex into hexagonal packing occurs before the phase transition
      accompanied with a change in molecular orientation. The phase transition behavior
      of the LB films is varied from a small temperature interval to large one
      depending on the hydrogen bond and metal complex.

PMID- 15267300
TI  - Structure and diffusion in amorphous aluminum silicate: a molecular dynamics
      computer simulation.
AB  - The amorphous aluminum silicate (Al2O3)2(SiO2) [AS2] is investigated by means of
      large scale molecular dynamics computer simulations. We consider fully
      equilibrated melts in the temperature range 6100 K> or =T> or =2300 K as well as
      glass configurations that were obtained from cooling runs from T=2300 to 300 K
      with a cooling rate of about 10(12) K/s. Already at temperatures as high as 4000
      K, most of the Al and Si atoms are fourfold coordinated by oxygen atoms. Thus,
      the structure of AS2 is that of a disordered tetrahedral network. The packing of
      AlO4 tetrahedra is very different from that of SiO4 tetrahedra in that Al is
      involved with a relatively high probability in small-membered rings and in
      triclusters in which an O atom is surrounded by four cations. We find as typical
      configurations two-membered rings with two Al atoms in which the shared O atoms
      form a tricluster. On larger length scales, the system shows a microphase
      separation in which the Al-rich network structure percolates through the SiO2
      network. The latter structure gives rise to a prepeak in the static structure
      factor at a wave number q=0.5 A(-1). A comparison of experimental x-ray data with
      the results from the simulation shows good agreement for the structure function.
      The diffusion dynamics in AS2 is found to be much faster than in SiO2. We show
      that the self-diffusion constants for O and Al are very similar and that they are
      by a factor of 2-3 larger than the one for Si.

PMID- 15267301
TI  - Studies of translational diffusion in the smectic A phase of a Gay-Berne mesogen
      using molecular dynamics computer simulation.
AB  - Molecular dynamics computer simulations are used to determine the self-diffusion
      coefficients for a Gay-Berne model mesogen GB (4.4,20,1,1) in the isotropic,
      nematic and smectic A phases along two isobars. The values of the parallel and
      perpendicular diffusion coefficients, D(parallel) and D(perpendicular), are
      calculated and compared in the different phases. For the phase sequence isotropic
      smectic A, D(perpendicular)*> or =D(parallel)* over the whole smectic A range
      with the ratio D(parallel)*/D(perpendicular)* decreasing with decreasing
      temperature. At a higher pressure, a nematic phase is observed between these two
      phases and we find that D(parallel)*>D(perpendicular)* throughout the nematic
      region and the inequality D(parallel)*>D(perpendicular)* remains on entering the
      smectic A phase. However, the ratio D(parallel)*/D(perpendicular)* decreases with
      decreasing temperature within the smectic A range and eventually this ratio
      inverts such that D(perpendicular)*>D(parallel)* at low temperatures. The
      temperature dependence of the parallel diffusion coefficient in the smectic A
      phase for this model mesogen is compared to that predicted by a theoretical model
      for diffusion subject to a cosine potential.

PMID- 15267302
TI  - Precipitation of oppositely charged polyelectrolytes in salt solutions.
AB  - We study phase separation in symmetric solutions of weakly charged flexible
      chains of opposite sign. Precipitation is caused by effective attractions due to
      charge fluctuations and by short-range attractions between monomers. The
      contribution from charge fluctuations is computed within the random phase
      approximation (RPA), which takes into account the connectivity of charges in the
      polyions. The impenetrability of the ions is accounted for by using a modified
      Coulomb potential in the RPA. In good solvent conditions the precipitate
      monotonically swells and eventually dissolves upon addition of salt. However,
      near the theta-solvent condition, but still in the good solvent, the precipitate
      can be stable at any salt concentration. Moreover, the density of the precipitate
      after initial decrease can increase with addition of salt. This effect is a
      result of redistribution of salt between the precipitate and the supernatant,
      which is due to an interplay of electrostatic and hardcore interactions. For not
      too weakly charged polyions the precipitate properties become strongly dependent
      on temperature even in good solvent conditions.

PMID- 15267303
TI  - Surface forces in polymer fluids: a comparison between simulations and density
      functional theory.
AB  - A polymer density functional theory is evaluated in terms of its ability to
      predict interactions between large surfaces in a polymer fluid. Comparisons are
      made with results from simulations in an expanded isotension ensemble. The
      variation of the net surface-surface interaction with adsorption strength is
      examined. Cases where the monomers interact via a pure hard sphere potential are
      investigated, but we have also studied the effect of attractions between the
      monomers. In all cases, we obtain an almost quantitative agreement between the
      simulated results and the predictions from the polymer density functional theory.

PMID- 15267304
TI  - Generalized-ensemble simulations of the human parathyroid hormone fragment PTH(1
      34).
AB  - A generalized-ensemble technique, multicanonical sampling, is used to study the
      folding of a 34-residue human parathyroid hormone fragment. An all-atom model of
      the peptide is employed and the protein-solvent interactions are approximated by
      an implicit solvent. Our results demonstrate that generalized-ensemble
      simulations are well suited to sample low-energy structures of such large
      polypeptides. Configurations with a root-mean-square deviation to the crystal
      structure of less than 1 A are found. Finally, we discuss limitations of our
      implicit solvent model.

PMID- 15267305
TI  - Phenylene ring dynamics in bisphenol-A-polysulfone by neutron scattering.
AB  - We have investigated the dynamics of phenylene rings in a glassy polysulfone
      (bisphenol-A-polysulfone) by means of quasielastic neutron scattering. Nowadays
      it is well known that these molecular motions are directly connected with the
      mechanical properties of engineering thermoplastics in general. The particular
      system investigated by us has the advantage that by selective deuteration of the
      methyl groups, the neutron scattering measured is dominated by the incoherent
      contribution from the protons in the phenylene rings. In this way, the dynamics
      of such molecular groups can be experimentally isolated. Two different types of
      neutron spectrometers: time of flight and backscattering, were used in order to
      cover a wide dynamic range, which extends from microscopic (10(-13) s) to
      mesoscopic (10(-9) s) times. Moreover, neutron diffraction experiments with
      polarization analysis were also carried out in order to characterize the
      structural features of the sample investigated. Fast oscillations of increasing
      amplitude with temperature and pi-flips are identified for phenylene rings
      motions. Due to the structural disorder characteristic of the amorphous state,
      both molecular motions display a broad distribution of relaxation times, which
      spreads over several orders of magnitude. Based on the results obtained, we
      propose a model for phenylene rings dynamics, which combines the two kinds of
      molecular motions identified. This model nicely describes the neutron scattering
      results in the whole dynamic range investigated.

PMID- 15267306
TI  - Molecular dynamics study of the thermal and the density effects on the local and
      the large-scale motion of polymer melts: scaling properties and dielectric
      relaxation.
AB  - Results from a molecular dynamics simulation of a melt of unentangled polymers
      are presented. The translational motion, the large-scale and the local
      reorientation processes of the chains, as well as their relations with the so
      called "normal" and "segmental" dielectric relaxation modes are thoroughly
      investigated in wide temperature and pressure ranges. The thermodynamic states
      are well fitted by the phenomenological Tait equation of state. A global time
      temperature-pressure superposition principle of both the translational and the
      rotational dynamics is evidenced. The scaling is more robust than the usual Rouse
      model. The latter provides insight but accurate comparison with the simulation
      calls for modifications to account for both the local chain stiffness and the
      nonexponential relaxation. The study addresses the issue whether the temperature
      or the density is a dominant control parameter of the dynamics or the two
      quantities give rise to comparable effects. By examining the ratio
      /alphatau//alphaP between the isochronic and isobaric expansivities, one finds
      that the temperature is dominant when the dynamics is fast. If the relaxation
      slows down, the fluctuations of the free volume increase their role and become
      comparable to those of the thermal energy. Detectable cross-correlation between
      the "normal-mode" and the "segmental" dielectric relaxations is found and
      contrasted with the usual assumption of independent modes.

PMID- 15267307
TI  - 1H multiple-quantum nuclear magnetic resonance investigations of molecular order
      in polymer networks. II. Intensity decay and restricted slow dynamics.
AB  - We present an approach towards the analysis of the intensity decay in proton
      multiple-quantum experiments on polymeric networks in terms of slow fluctuations
      of the residual dipole-dipole coupling tensor. Solutions for individual spin
      pairs as well as the three-spin system of methyl groups are derived, and the
      influence of the cycle time of the multiple-quantum pulse sequence is evaluated.
      The multiple-quantum strategy discussed herein features the advantage that the
      magnitude of the fluctuating part of the residual dipole-dipole coupling constant
      and the correlation time of the slow process can be determined independently of
      the integral residual coupling constant as well as its distribution. The theory
      is applied to experiments on end-linked poly(dimethylsiloxane) model networks
      with mono- and bimodal chain length distributions, where it is found that, for
      all samples, correlation times of the slow processes average to about 1 ms, and
      that the magnitude of the fluctuating part of the dipole-dipole coupling is
      significantly smaller than the average dipole-dipole coupling constant. This
      observation is interpreted in terms of considerably restricted reorientations of
      topological constraints.

PMID- 15267308
TI  - Spatial regimes in the dynamics of polyolefins: self-motion.
AB  - Molecular dynamics simulations are used to investigate the spatial dependence of
      dynamics in a series of polyolefins. The dynamic indicator used is the self
      intermediate scattering function, which parallels the observable in an incoherent
      quasielastic neutron scattering experiment such as time of flight or
      backscattering. As with neutron time of flight experiments, two processes are
      evident. The fast process is a single exponential, and has relaxation times that
      scale as q(-2), where q is the momentum transfer. The slow process is the
      stretched exponential decay usually associated with the motion underlying the
      glass transition. The stretching exponent is a function of spatial scale, with
      the minimum values occurring near the spatial scale of interchain packing.
      Relaxation times for the slow process scale as q(-2/beta) for all materials
      investigated. The relative contribution of the two processes is a function of
      spatial scale, with the crossover from fast to slow dynamics at the location of
      closest possible interchain contacts, which is approximately three times the cage
      size. These observations apply equally well to the four materials considered. We
      consider the relative ordering of relaxation times of the series in light of
      their local chain architecture. This ordering varies depending on the observable
      calculated..

PMID- 15267309
TI  - Microscopic theory of orientational order, structure and thermodynamics in
      strained polymer liquids and networks.
AB  - A microscopic integral equation theory of the segmental orientational order
      parameter, structural correlations and thermodynamics of strained polymer
      solutions, melts and networks has been developed. The nonclassical problem of the
      consequences of intermolecular excluded volume repulsions and chain connectivity
      is addressed. The theory makes several novel predictions, including effective
      power law dependences of the orientational order parameter on monomer
      concentration and chain degree of polymerization, and strain hardening of the
      bulk modulus. The predictions of a nearly classical strain dependence, and
      supralinear scaling with segment concentration, of the strain-induced nematic
      order parameter is in agreement with nuclear magnetic resonance experiments. The
      absolute magnitudes of the a priori calculated orientational order parameter
      agree with simulations and experiments to within a factor of 2. The possible
      complicating influence of "trapped entanglements" in crosslinked networks is
      discussed. Extensions of the theory are possible to treat the mechanical response
      of flexible polymer liquids and rubbers, and the structure, thermodynamics, and
      mechanical properties of strained liquid crystal forming polymers.

PMID- 15267310
TI  - Configurational bias Monte Carlo simulation of phase segregation in block
      copolymer networks.
AB  - Cross-linked block copolymers are used as adhesives in fiber-reinforced composite
      material manufactures for automotive applications. Good adhesion between the
      polymer matrix and fibers in the interphase region is required for the structural
      integrity of these materials. Experimental evidence indicates that superior
      adhesion is obtained when phase segregation occurs between the two matrix phase
      block copolymers. It is therefore desirable to predict the conditions under which
      phase segregation is expected to occur. Configurational bias Monte Carlo
      simulations of two-component, trifunctional block copolymer networks were carried
      out to investigate phase segregation in these materials. The effects of four
      principal parameters on phase segregation were examined: the weight fractions of
      the two components, the cross-link length, the connectivity of the network, and
      the ratio of the square-well interactions. The molecular simulation results
      confirmed trends observed in laboratory measurements.

PMID- 15267311
TI  - Voronoi space division of a polymer: topological effects, free volume, and
      surface end segregation.
AB  - In order to investigate the topological effects of chain molecules, united-atom
      molecular dynamics simulations of a 500-mer polyethylene linked by 50 hexyl
      groups (a grafted polymer having 52 ends) are carried out and analyzed in terms
      of Voronoi space division. We find that the volume of a Voronoi polyhedron for a
      chain end is larger than that for an internal or junction atom, and that it is
      the most sensitive to temperature, both of which suggest higher mobility of chain
      ends. Moreover, chain ends dominantly localize at the surface of the globule: The
      striking evidence is that while the ratio of surface atoms is only 24% of all
      atoms, the ratio of ends at the surface is 91% out of all ends. The shape of
      Voronoi polyhedra for internal atoms is prolate even in the bulk, and near the
      surface it becomes more prolate. We propose the concept of bonding faces, which
      play a significant role in the Voronoi space division of covalently bonding
      polymers. Two bonding faces occupy 38% of the total surface area of a Voronoi
      polyhedron and determine the prolate shape.

PMID- 15267312
TI  - Evaluating the accuracy of a density functional theory of polymer solutions with
      additive hard sphere diameters.
AB  - We assess the accuracy of a density functional theory for athermal polymer
      solutions, consisting of solvent particles with a smaller radius than that of the
      monomers. The monomer and solvent density profiles in a slit bound by hard, flat,
      and inert surfaces are compared with those obtained by a Metropolis Monte Carlo
      simulation. At the relatively high density at which the comparison is performed,
      there are considerable packing effects at the walls. The density functional
      theory introduces a simple weight function to describe nonlocal correlations in
      the fluid. A recent study of surface forces in polymer solutions used a different
      weighting scheme to that proposed in this article, leading to less accurate
      results. The implications of the conclusions of that study are discussed.

PMID- 15267313
TI  - Photoelectron circular dichroism in core level ionization of randomly oriented
      pure enantiomers of the chiral molecule camphor.
AB  - The inner-shell photoionization of unoriented camphor molecules by circularly
      polarized light has been investigated from threshold to a photoelectron kinetic
      energy of approximately 65 eV. Photoelectron spectra of the carbonyl C 1s
      orbital, recorded at the magic angle of 54.7 degrees with respect to the light
      propagation direction, show an asymmetry of up to 6% on change of either the
      photon helicity or molecular enantiomer. These observations reveal a circular
      dichroism in the angle resolved emission with an asymmetry between forward and
      backward scattering (i.e., 0 degrees and 180 degrees to the light beam) which can
      exceed 12%. Since the initial state is an atomiclike spherically symmetric
      orbital, this strongly suggests that the asymmetry is caused by final-state
      effects dependent on the chiral geometry of the molecule. These findings are
      confirmed by electron multiple scattering calculations of the photoionization
      dynamics in the electric-dipole approximation.

PMID- 15267314
TI  - Soft electron impact ionization in crossed molecular beam reactive scattering:
      the dynamics of the O((3)P)+C(2)H(2) reaction.
AB  - Soft ionization by low-energy, tunable electrons is implemented for the first
      time in crossed molecular beam reactive scattering experiments with mass
      spectrometric detection. The power of the method, which permits the suppression
      of the dissociative ionization of interfering species, is exemplified with the
      study of the O((3)P)+C(2)H(2) multichannel reaction.

PMID- 15267315
TI  - Time-dependent probability of quantum tunneling in terms of the
      quasisemiclassical method.
AB  - In view of the rapid progress in experiments of the tunneling dynamics in the
      time domain, we develop a quasisemiclassical method that is aimed at a study of
      the proton-transfer dynamics in a large system such as tropolone and its
      interesting derivatives, to which not only full quantum mechanics, but even a
      standard semiclassical theory is never easy to apply. In our very tractable
      method for multidimensional systems, the tunneling paths are generated in terms
      of the generalized classical mechanics, but the quantum phases arising from the
      action integral, the Maslov index, and the semicalssical amplitude factor as well
      in the semiclassical kernels are entirely neglected. This approach is called the
      quasisemiclassical method. One of the technical issues involved in the general
      semiclassical scheme is how to locate points from which a tunneling path
      emanates. Hence the studies of such tunneling points and the quasisemiclassical
      method should be examined collectively. We test several ways of determining the
      tunneling point, including those already proposed in the literature and a newly
      proposed one. It is shown numerically that the quasisemiclassical method with an
      appropriate choice of tunneling points reproduces the full quantum mechanical
      tunneling probability reasonably well. This case study indicates that the present
      conventional approach is promising to the study of large systems. The role of
      tunneling points in the initial process of tunneling is also discussed.

PMID- 15267316
TI  - Interfacing Brownian dynamics simulations.
AB  - Starting from the flux of particles in a Brownian dynamics simulation we derive
      boundary conditions, which allow us (i) to couple a Brownian dynamics calculation
      to a reservoir of particles of a given density, i.e., setting up constant density
      boundary conditions, and (ii) to build an interface between Brownian dynamics and
      a diffusional treatment of adjacent simulation volumes. With these algorithms it
      is sometimes possible to dramatically reduce the system size--and therefore the
      necessary resources--of multiparticle Brownian dynamics calculations. In this
      paper we give one-dimensional examples which illustrate potential applications
      and savings.

PMID- 15267317
TI  - Two-electron integrations in the quantum theory of atoms in molecules.
AB  - A method to compute two-electron integrals over arbitrary regions of space is
      introduced and particularized to the basins appearing in the quantum theory of
      atoms in molecules. The procedure generalizes the conventional multipolar
      approach to account for overlapping densities. We show that the approach is
      always convergent and computationally efficient, scaling as N(4) in the worst,
      two-center case. Several numerical results supporting our claims are also
      presented.

PMID- 15267318
TI  - Potential--energy surfaces for excited states in extended systems.
AB  - With a simple and physically intuitive method, first-principles calculations of
      potential-energy surfaces are performed for excited states in a number of
      illustrative systems, including dimers (H(2) and NaCl) and gas-surface systems
      [Cl-Na(100) and Cl(2)-Na(100)]. It is based on density-functional theory and is a
      generalization of the Delta self-consistent field (DeltaSCF) method, where
      electron-hole pairs are introduced in order to model excited states,
      corresponding to internal electron transfers in the considered system. The
      desired excitations are identified by analysis of calculated electron orbitals,
      local densities of states, and charge densities. For extended systems, where
      reliable first-principles methods to account for electronically excited states
      have so far been scarce, our method is very promising. Calculated results, such
      as the chemiluminescence of halogen molecules impinging on a alkali-metal
      surface, and the vertical (5 sigma-->2 pi(*)) excitation within the adsorbed CO
      molecule on the Pd(111) surface, are in working agreement with those of other
      studies and experiments.

PMID- 15267319
TI  - Effects of higher order Jahn-Teller coupling on the nuclear dynamics.
AB  - In this paper effects of higher order Jahn-Teller coupling terms on the
      nonadiabatic dynamics are studied. Of particular interest is the case when the
      potential energy surfaces of the degenerate state show pronounced anharmonicity.
      In order to demonstrate the effects a two-dimensional E multiply sign in circle e
      Jahn-Teller model system is treated which is based on the e(') stretching
      vibration of the photoactive (2)E(') state of NO(3) as a realistic example. The
      sixth order E multiply sign in circle e Jahn-Teller Hamiltonian is derived in the
      diabatic representation which is valid for any system with a C(3) rotation axis.
      This diabatization scheme is compared to lower-order Jahn-Teller Hamiltonians and
      to symmetry adapted as well as ad hoc approximations. Lower-order potentials
      result in pronounced quantitative and qualitative differences in the dynamics,
      including differences in the evolution of mean values, the autocorrelation
      functions (and thus the corresponding spectra), and the electronic population
      evolution. In the particular example treated, the results of fourth and fifth
      order potentials are very similar to the sixth order reference system. In
      contrast, the approximate sixth order Hamiltonians, though the corresponding
      adiabatic surfaces seem to be nearly identical, results in pronounced
      differences. The possible consequences for the dynamics of realistic systems with
      higher dimensionality are briefly discussed.

PMID- 15267320
TI  - On the calculation of single-particle time correlation functions from Bose
      Einstein centroid dynamics.
AB  - The calculation of single-particle time correlation functions using the Bose
      Einstein centroid dynamics formalism is discussed. A new definition of the
      quasidensity operator is used to calculate the centroid force on a given particle
      for an anharmonic system. The force includes correlation effects due to quantum
      statistics and is used for the calculation of the classical-like dynamics of
      phase-space centroid variables within the centroid molecular dynamics
      approximation. Time correlation functions are then obtained for single-particle
      quantities. These correspond to the double-Kubo transform of exact quantum
      mechanical correlation functions. The centroid dynamics results are compared to
      those of exact basis-set calculations and a good agreement is found. The level of
      accuracy is in fact the same as what was observed earlier for the calculation of
      center-of-mass correlation functions for Fermi-Dirac and Bose-Einstein
      statistics, and for any correlation function for Boltzmann statistics. These
      results show that it is now possible to use Bose-Einstein centroid molecular
      dynamics to calculate single-particle correlation functions for systems where
      quantum exchange effects are present.

PMID- 15267321
TI  - Calibration of the n-electron valence state perturbation theory approach.
AB  - Extensive tests have been performed to benchmark and to compare with second-order
      perturbation theory based on a complete active space self-consistent field
      reference function (CASPT2), the recently developed n-electron valence state
      perturbation theory at second order (NEVPT2). Test calculations included the
      group fifteen diatomic molecules X(2) (X=N, P, As, and Sb) and the (4)S/(2)D and
      (4)S/(2)P splittings for the corresponding atoms, the (1)A(1)-(3)B(1) splittings
      for CH(2) and SiH(2), and the absorption spectra of pyrrole and of
      Cu(Imidazole)(2)(SH)(SH(2))(+), which is a model for plastocyanin. Comparisons
      with full configuration-interaction calculations and experimental data show that
      the accuracy of NEVPT2 is in most cases even better than CASPT2. Where intruder
      states hamper the CASPT2 calculations, NEVPT2 performs significantly better. Care
      is needed in the choice of active orbitals, for example in the calculation of the
      (4)S/(2)D and (4)S/(2)P splittings for the group fifteen atoms. This is due to
      the different treatment of orbitals belonging to the inactive or active spaces,
      making the NEVPT2 not invariant for the choice of active space, even in cases
      where the multiconfiguration self-consistent field energy is invariant.

PMID- 15267322
TI  - Iterative solutions with energy selected bases for highly excited vibrations of
      tetra-atomic molecules.
AB  - The use of energy selected bases (ESB) with iterative diagonalization of the
      Hamiltonian matrix is described for vibrations of tetra-atomic systems. The
      performance of the method is tested by computing vibrational states of HOOH below
      10,000 cm(-1) (1296 A+ symmetry states) and H(2)CO below 13,500 cm(-1) (729 A(1)
      symmetry states). For iterative solutions, we tested both the implicitly
      restarted Lanczos method (IRLM) and the standard (nonreorthogonalizing) Lanczos
      approach. Comparison with other contracted basis approach as well as direct
      product grid representation shows superior performance of the ESB/IRLM approach.
      Of the two systems, H(2)CO is found to be more challenging than HOOH since it has
      much stronger couplings among vibrational modes, which leads to a drastically
      larger primitive basis set. For H(2)CO we also discuss some interesting behavior
      of the molecule in the high internal energy regime.

PMID- 15267323
TI  - Rotation-tunneling analysis of the origin band in the tropolone pi(*)<--pi
      absorption system.
AB  - The tunneling-split origin band of the tropolone A (1)B(2)-X (1)A(1) (pi(*)<--pi)
      absorption system was interrogated under ambient, bulk-gas conditions by
      exploiting high-resolution degenerate four-wave mixing techniques. The inherent
      complexity of this spectral region was alleviated by performing polarization
      resolved measurements, with judicious selection of transverse characteristics for
      the incident and detected electromagnetic fields enabling rovibronic transitions
      to be discriminated according to their attendant changes in rotational angular
      momentum, DeltaJ. Quantitative simulation of recorded data sets showed the
      vibrationless level of the electronically excited state to be bifurcated by
      Delta(0) (A)=19.846(25) cm(-1), representing a factor of 20 increase in proton
      transfer efficiency over the corresponding level of the ground electronic state.
      Spectroscopic parameters extracted for the 0(+) and 0(-) manifolds of A (1)B(2)
      tropolone yield unexpectedly large values of the inertial defect, DeltaI(0(+) )
      (A)=-0.802(86) amu A(2) and DeltaI(0(-) ) (A)=-0.882(89) amu A(2), strongly
      suggesting that a loss of molecular planarity accompanies the pi(*)<--pi electron
      promotion. These results, as well as complementary information deduced for
      interloping hot-band resonances, are discussed in terms of the unique structural
      and dynamical properties exhibited by tropolone and related proton-transfer
      species.

PMID- 15267324
TI  - Differential, partial and total electron impact ionization cross sections for
      SF(6).
AB  - Single and double differential ionization cross sections for the production of
      ions resulting from dissociative, single and double ionization of SF(6) by
      electron impact have been calculated using a semiempirical formulation based on
      the Jain-Khare approach. In addition, triple differential cross sections have
      been obtained for some of the doubly charged fragment ions at an incident
      electron energy of 100, 150, and 200 eV, respectively, and a fixed scattering
      angle of 30 degrees. As no previous data seem to exist for differential cross
      sections we have derived from these differential cross sections corresponding
      partial and total ionization cross sections from threshold up to 900 eV and
      compared those with the available theoretical and experimental data.

PMID- 15267325
TI  - Vibrational spectra of germanium-carbon clusters. II. GeC(7) and GeC(9).
AB  - Experimental and theoretical studies of a novel family of germanium-carbon
      clusters (Ge(n)C(m)) that were initiated with our earlier identification of the
      GeC(3)Ge cluster have now been extended to the GeC(7) and GeC(9) chains. The new
      clusters, which were formed by laser ablation and trapped in solid Ar at
      approximately 10 K, have been identified using Fourier-transform infrared (FTIR)
      measurements coupled with density-functional theory (DFT) calculations. The
      nu(1)(sigma) vibrational fundamental of linear GeC(7) has been identified at
      2063.6 cm(-1), and an absorption at 1928.3 cm(-1) has been assigned to the
      nu(4)(sigma) fundamental of linear GeC(9). FTIR measurements of the isotopic
      shifts for the assignments are in good agreement with the DFT predictions.

PMID- 15267326
TI  - Dynamic pathway model for the formation of C(60).
AB  - We present a dynamic pathway model for the formation of C(60) using the action
      derived molecular dynamics simulations. We propose candidate precursors for
      dynamic pathway models in which carbons spontaneously aggregate due to favorable
      energetics and kinetics. Various planar polycyclic models are in a
      disadvantageous state where they cannot be trapped in the forward reaction due to
      their high excess internal energies. Our simulation results show that precursors
      either in the shape of tangled polycyclics or in the shape of open cages are
      kinetically favored over precursors in the shape of planar hexagonal graphite
      fragments. Calculated activation energies for the probable precursor models are
      in good agreement with experiment. Existence of chains in the models of tangled
      polycyclics and open cages is beneficially for the formation of C(60) molecule.
      Chains attached to the precursor model are energetically favorable and display
      lithe movements along the dynamic pathway.

PMID- 15267327
TI  - The 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) states of the SO(2) (+) ion studied using
      multiconfiguration second-order perturbation theory.
AB  - The 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) electronic states of the SO(2) (+) ion
      have been studied using multiconfiguration second-order perturbation theory
      (CASPT2) and two contracted atomic natural orbital basis sets,
      S[6s4p3d1f]/O[5s3p2d1f] (ANO-L) and S[4s3p2d]/O[3s2p1d] (ANO-S), and the three
      states were considered to correspond to the observed X, B, and A states,
      respectively, in the previous experimental and theoretical studies. Based on the
      CASPT2/ANO-L adiabatic excitation energy calculations, the X, A, and B states of
      SO(2) (+) are assigned to 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2), respectively, and
      our assignments of the A and B states are contrary to the previous assignments (A
      to (2)A(2) and B to (2)B(2)). The CASPT2/ANO-L energetic calculations also
      indicate that the 1 (2)A(1), 1 (2)B(2), and 1 (2)A(2) states are, respectively,
      the ground, first excited, and second excited states at the ground-state (1
      (2)A(1)) geometry of the ion and at the geometry of the ground-state SO(2)
      molecule. Based on the CASPT2/ANO-L results for the geometries, we realize that
      the experimental geometries (determined by assuming the bond lengths to be the
      same as the neutral ground state of SO(2)) were not accurate. The CASPT2/ANO-S
      calculations for the potential energy curves as functions of the OSO angle
      confirm that the 1 (2)B(2) and 1 (2)A(2) states are the results of the Renner
      Teller effect in the degenerate (2)Pi(g) state at the linear geometry, and it is
      clearly shown that the 1 (2)B(2) curve, as the lower component of the Renner
      splitting, lies below the 1 (2)A(2) curve. The UB3LYP/cc-pVTZ adiabatic
      excitation energy calculations support the assignments (A to (2)B(2) and B to
      (2)A(2)) based on the CASPT2/ANO-L calculations.

PMID- 15267328
TI  - Binding energies of small lithium clusters (Li(n)) and hydrogenated lithium
      clusters (Li(n)H).
AB  - Large coupled cluster computations utilizing the Dunning weighted correlation
      consistent polarized core-valence (cc-pwCVXZ) hierarchy of basis sets have been
      conducted, resulting in a panoply of internally consistent geometries and
      atomization energies for small Li(n) and Li(n)H (n=1-4) clusters. In contrast to
      previous ab initio results, we predict a monotonic increase in atomization
      energies per atom with increasing cluster size for lithium clusters, in
      accordance with the historical Knudsen-effusion measurements of Wu. For
      hydrogenated lithium clusters, our results support previous theoretical work
      concerning the relatively low atomization energy per atom for Li(2)H compared to
      LiH and Li(3)H. The CCSD(T)/cc-pwCVQZ atomization energies for LiH, Li(2)H,
      Li(3)H, and the most stable isomer of Li(4)H, including zero-point energy
      corrections, are 55.7, 79.6, 113.0, and 130.6 kcal/mol, respectively. The latter
      results are not consistent with the most recent experiments of Wu.

PMID- 15267329
TI  - Dissociation of hydrogen fluoride in HF(H(2)O)(7).
AB  - We have previously demonstrated that H-bond arrangement has a significant
      influence on the energetics, structure and chemistry of water clusters. In this
      work, the effect of H-bond orientation on the dissociation of hydrogen fluoride
      with seven water molecules is studied by means of graph theory and high level ab
      initio methods. It is found that cubic structures of HF(H(2)O)(7) are more stable
      than structures of other topologies reported in the literature. Electronic
      calculations on all possible H-bond orientations of cubie-HF(H(2)O)(7) show that
      ionized structures are energetically more favorable than nonionized ones. This is
      an indication that seven water molecules might be capable of ionizing hydrogen
      fluoride.

PMID- 15267330
TI  - Bond-selective photodissociation of partially deuterated ammonia molecules:
      photodissociations of vibrationally excited NHD(2) in the 5nu(NH) state and
      NH(2)D in the 5nu(ND) state.
AB  - Ultraviolet photodissociation of NHD(2) excited to the fourth overtone state of
      the NH stretching mode (5nu(NH)) and NH(2)D excited to that of the ND stretching
      mode (5nu(ND)) has been investigated by using a crossed laser and molecular beams
      method. Branching ratio between the NH and ND bond dissociations has been
      determined by utilizing a (2+1) resonance enhanced multiphoton ionization scheme
      of H and D atoms. For the photolysis of NHD(2) in the 5nu(NH) state, the NH
      dissociation cross section is 5.1+/-1.4 times as large as the ND dissociation
      cross section per bond. On the other hand, for the photolysis of NH(2)D in the
      5nu(ND) state, the ratio of the NH dissociation cross section per bond to the ND
      dissociation cross section decreases to 0.68+/-0.16. In comparison with the
      branching ratios for the photolysis of vibrationally unexcited NH(2)D and NHD(2),
      the present results indicate that the excitation of the NH stretching mode
      enhances the NH dissociation with ca. two times larger NH/ND branching ratio,
      whereas the excitation of the ND stretching mode results in the preferential ND
      dissociation with ca. 3-4 times larger ND/NH branching ratio than that for the
      vibrational ground states. The mechanism of the bond-selective enhancement has
      been discussed in terms of the energetics and dynamics of wave packet.

PMID- 15267331
TI  - Ab initio analytical potential energy surface and quasiclassical trajectory study
      of the O(+)((4)S)+H(2)(X (1)Sigma(g) (+))-->OH(+)(X (3)Sigma(-))+H((2)S) reaction
      and isotopic variants.
AB  - An analytical potential energy surface (PES) representation of the
      O(+)((4)S)+H(2)(X (1)Sigma(g) (+)) system was developed by fitting around 600
      CCSD(T)/cc-pVQZ ab initio points. Rate constant calculations for this reaction
      and its isotopic variants (D(2) and HD) were performed using the quasiclassical
      trajectory (QCT) method, obtaining a good agreement with experimental data.
      Calculations conducted to determine the cross section of the title reaction,
      considering collision energies (E(T)) below 0.3 eV, also led to good accord with
      experiments. This PES appears to be suitable for kinetics and dynamics studies.
      Moreover, the QCT results show that, although the hypotheses of a widely used
      capture model are not satisfied, the resulting expression for the cross section
      can be applied within a suitable E(T) interval, due to errors cancellation. This
      could be a general situation regarding the application of this simple model to
      ion-molecule processes.

PMID- 15267332
TI  - The rotational spectrum and theoretical study of a dinuclear complex,
      MnRe(CO)(10).
AB  - The first rotational spectrum of a dinuclear complex, MnRe(CO)(10), has been
      obtained using a high-resolution pulsed beam microwave spectrometer. Sixty-four
      hyperfine components of the J=11-->J(')=12 and J=12-->J(')=13 rotational
      transitions were measured for two rhenium isotopomers. The B values obtained from
      the experiment are B=200.36871(18) MHz for the (187)Re isotopomer and
      B=200.5561(10) MHz for the (185)Re isotopomer. The measured rotational constants
      are in reasonably good agreement with the B values calculated from the x-ray
      diffraction structural data, and from theoretical calculations. The gas-phase Mn
      Re bond distance is approximately 2.99 A, and the calculated value is only
      slightly longer. The experimental quadrupole coupling constant for the manganese
      atom is eQq(aa) ((55)Mn)=-16.52(5) MHz, and the corresponding quadrupole coupling
      constants for the two rhenium isotopomers are eQq(aa) ((187)Re)=370.4(4) MHz and
      eQq(aa) ((185)Re)=390.9(6) MHz. The quadrupole coupling constants were also
      determined from a variety of theoretical calculations, with very large Gaussian
      orbital bases. The best estimates, at a nonrelativistic level, are eQq(aa)
      ((55)Mn)=0.68 MHz and eQq(aa) ((187)Re)=327.6 MHz with a 874 GTO basis set, but
      the results are very basis set dependent, especially the sign of the Mn
      quadrupole coupling. Very slight bending of angles MnC(eq)O(eq) and ReC(eq)O(eq)
      angles is found in the calculations.

PMID- 15267333
TI  - Low-lying electronic states of FeNC and FeCN: a theoretical journey into
      isomerization and quartet/sextet competition.
AB  - With several levels of multireference and restricted open-shell single-reference
      electronic structure theory, optimum structures, relative energetics, and
      spectroscopic properties of the low-lying (6)Delta, (6)Pi, (4)Delta, (4)Pi, and
      (4)Sigma(-) states of linear FeNC and FeCN have been investigated using five
      contracted Gaussian basis sets ranging from Fe[10s8p3d], C/N[4s2p1d] to
      Fe[6s8p6d3f2g1h], C/N[6s5p4d3f2g]. Based on multireference configuration
      interaction (MRCISD+Q) results with a correlation-consistent polarized valence
      quadruple-zeta (cc-pVQZ) basis set, appended with core correlation and
      relativistic corrections, we propose the relative energies: T(e)(FeNC),
      (6)Delta(0)<(6)Pi (2300 cm(-1))<(4)Delta (2700 cm(-1))<(4)Pi (4200 cm(
      1))<(4)Sigma(-); and T(e)(FeCN), (6)Delta(0)<(6)Pi (1800 cm(-1))<(4)Delta (2500
      cm(-1))<(4)Pi (2900 cm(-1))<(4)Sigma(-). The (4)Delta and (4)Pi states have
      massive multireference character, arising mostly from 11sigma-->12sigma
      promotions, whereas the sextet states are dominated by single electronic
      configurations. The single-reference CCSDT-3 (coupled cluster singles and doubles
      with iterative partial triples) method appears to significantly overshoot the
      stabilization of the quartet states provided by both static and dynamical
      correlation. The (4,6)Delta and (4,6)Pi states of both isomers are rather ionic,
      and all have dipole moments near 5 D. On the ground (6)Delta surface, FeNC is
      predicted to lie 0.6 kcal mol(-1) below FeCN, and the classical barrier for
      isocyanide/cyanide isomerization is about 6.5 kcal mol(-1). Our data support the
      recent spectroscopic characterization by Lei and Dagdigian [J. Chem. Phys. 114,
      2137 (2000)] of linear (6)Delta FeNC as the first experimentally observed
      transition-metal monoisocyanide. Their assignments for the ground term symbol,
      isotopomeric rotational constants, and the Fe-N omega(3) stretching frequency are
      confirmed; however, we find rather different structural parameters for (6)Delta
      FeNC:r(e)(Fe-N)=1.940 A and r(N-C)=1.182 A at the cc-pVQZ MRCISD+Q level. Our
      results also reveal that the observed band of FeNC originating at 27 236 cm(-1)
      should have an analog in FeCN near 23 800 cm(-1) of almost equal intensity.
      Therefore, both thermodynamic stability and absorption intensity factors favor
      the eventual observation of FeCN via a (6)Pi<--(6)Delta transition in the near
      UV.

PMID- 15267334
TI  - Analytic solutions for Baxter's model of sticky hard sphere fluids within
      closures different from the Percus-Yevick approximation.
AB  - We discuss structural and thermodynamical properties of Baxter's adhesive hard
      sphere model within a class of closures which includes the Percus-Yevick (PY)
      one. The common feature of all these closures is to have a direct correlation
      function vanishing beyond a certain range, each closure being identified by a
      different approximation within the original square-well region. This allows a
      common analytical solution of the Ornstein-Zernike integral equation, with the
      cavity function playing a privileged role. A careful analytical treatment of the
      equation of state is reported. Numerical comparison with Monte Carlo simulations
      shows that the PY approximation lies between simpler closures, which may yield
      less accurate predictions but are easily extensible to multicomponent fluids, and
      more sophisticate closures which give more precise predictions but can hardly be
      extended to mixtures. In regimes typical for colloidal and protein solutions,
      however, it is found that the perturbative closures, even when limited to first
      order, produce satisfactory results.

PMID- 15267335
TI  - Ultrafast collective dynamics in the charge-density-wave conductor K(0.3)MoO(3).
AB  - Low-energy coherent charge-density wave excitations are investigated in blue
      bronze (K(0.3)MoO(3)) and red bronze (K(0.33)MoO(3)) by femtosecond pump-probe
      spectroscopy. A linear gapless, acousticlike dispersion relation is observed for
      the transverse phasons with a pronounced anisotropy in K(0.33)MoO(3). The
      amplitude mode exhibits a weak (opticlike) dispersion relation with a frequency
      of 1.67 THz at 30 K. Our results show for the first time that the time-resolved
      optical technique provides momentum resolution of collective excitations in
      strongly correlated electron systems.

PMID- 15267336
TI  - Diffusive dynamics of water in tert-butyl alcohol/water mixtures.
AB  - Quasielastic neutron scattering has been used to investigate the dynamical
      behavior of H(2)O in water/tert-butyl alcohol solutions. The measurements were
      made at fixed temperature (293 K) as a function of tert-butyl alcohol molar
      fraction, x, in the range 0-0.042. The data have been compared to those of pure
      water in the temperature range 269-293 K. The effect of tert-butyl alcohol
      addition on water dynamics is equivalent to that obtained by lowering the
      temperature of pure water by an amount proportional to the alcohol concentration.
      The temperature dependence of the diffusivity parameters in pure water and their
      concentration dependence in tert-butyl alcohol/water solutions can be rescaled to
      a common curve attributing to each solution a concentration-dependent "structural
      temperature" lower than the actual thermodynamic one. These results can be
      understood in terms of Stillinger's picture of water structuring and of other
      more recent theoretical pictures that emphasize the influence of the geometrical
      properties of hydrogen bond networks on water mobility.

PMID- 15267337
TI  - Femtosecond absorption study of photodissociation of diphenylcyclopropenone in
      solution: reaction dynamics and coherent nuclear motion.
AB  - Reaction dynamics and coherent nuclear motions in the photodissociation of
      diphenylcyclopropenone (DPCP) were studied in solution by time-resolved
      absorption spectroscopy. Subpicosecond transient absorption spectra were measured
      in the visible region with excitation at the second absorption band of DPCP. The
      obtained spectra showed a new short-lived band around 480 nm immediately after
      photoexcitation, which is assignable to the initially populated S(2) state of
      DPCP before the dissociation. The dissociation takes place from this excited
      state (the precursor of the reaction) with a time constant of 0.2 ps, and the
      excited state of diphenylacetylene (DPA) is generated as the reaction product.
      The transient absorption after the dissociation decayed with a time constant of 8
      ps that is very close to the S(2)-state lifetime of DPA, but the spectrum of this
      8-ps component was different from the S(2) absorption observed with direct
      photoexcitation of DPA. We conclude that the dissociation of DPCP generates the
      S(2) state of DPA that probably has a cis-bent structure. At later delay times
      (>30 ps), the transient absorption signals are very similar to those obtained by
      direct photoexcitation of DPA. This confirmed that the electronic relaxation from
      the S(2) state of the product DPA occurs in a similar manner to that of DPA
      itself, i.e., the internal conversion to the S(1) state and subsequent
      intersystem crossing to the T(1) state. In order to examine the coherent nuclear
      dynamics in this dissociation reaction, we carried out time-resolved absorption
      measurements for the 480-nm band with 70 fs resolution. It was found that an
      underdamped oscillatory modulation with a 0.1-ps period is superposed on the
      decay of the precursor absorption. This indicates that DPCP exhibits a coherent
      nuclear motion having a approximately 330-cm(-1) frequency in the dissociative
      excited state. Based on a comparison with the measured and calculated Raman
      spectra of ground-state DPCP, we discuss the assignment of the "330-cm(-1)
      vibration" and attribute it to a vibration involving the displacement of the CO
      group as well as the deformation of the Ph-C[Double Bond]C-Ph skeleton. We
      consider that this motion is closely related to the reaction coordinate of the
      photodissociation of DPCP.

PMID- 15267338
TI  - Elucidating the role of many-body forces in liquid water. I. Simulations of water
      clusters on the VRT(ASP-W) potential surfaces.
AB  - We test two new potentials for water, fit to vibration-rotation tunneling (VRT)
      data by employing diffusion quantum Monte Carlo simulations to calculate the
      vibrational ground-state properties of water clusters. These potentials, VRT(ASP
      W)II and VRT(ASP-W)III, are fits of the highly detailed ASP-W (anisotropic site
      potential with Woermer dispersion) ab initio potential to (D(2)O)(2) microwave
      and far-infrared data, and along with the SAPT5s (five-site symmetry adapted
      perturbation theory) potentials, are the most accurate water dimer potential
      surfaces in the literature. The results from VRT(ASP-W)II and III are compared to
      those from the original ASP-W potential, the SAPT5s family of potentials, and
      several bulk water potentials. Only VRT(ASP-W)III and the spectroscopically
      "tuned" SAPT5st (with N-body induction included) accurately reproduce the
      vibrational ground-state structures of water clusters up to the hexamer. Finally,
      the importance of many-body induction and three-body dispersion are examined, and
      it is shown that the latter can have significant effects on water cluster
      properties despite its small magnitude.

PMID- 15267339
TI  - Electron spin polarization of the excited quartet state of strongly coupled
      triplet-doublet spin systems.
AB  - The electron spin polarization associated with electronic relaxation in molecules
      with trip-quartet and trip-doublet excited states is calculated. Such molecules
      typically relax to the lowest trip-quartet state via intersystem crossing from
      the trip doublet, and it is shown that when spin-orbit coupling provides the main
      mechanism for this relaxation pathway it leads to spin polarization of the trip
      quartet. Analytical expressions for this polarization are derived using first-
      and second-order perturbation theory and are used to calculate powder spectra for
      typical sets of magnetic parameters. It is shown that both net and multiplet
      contributions to the polarization occur and that these can be separated in the
      spectrum as a result of the different orientation dependences of the +/-1/2<-->+/
      3/2 and +1/2<-->-1/2 transitions. The net polarization is found to be localized
      primarily in the center of the spectrum, while the multiplet contribution
      dominates in the outer wings. Despite the fact that the multiplet polarization is
      much stronger than the net polarization for individual orientations of the spin
      system, the difference in orientation dependence of the transitions leads to
      comparable amplitudes for the two contributions in the powder spectrum. The
      influence of this difference on the line shape is investigated in simulations of
      partially ordered samples. Because the initial nonpolarized state of the spin
      system is not conserved for the proposed mechanism, the net polarization can
      survive in the doublet ground state following electronic relaxation of the
      triplet part of the system.

PMID- 15267340
TI  - On the growth and shape of sodium taurodeoxycholate micellar aggregates: a spin
      label and quasielastic light scattering investigation.
AB  - Electron spin resonance (ESR) and quasielastic laser scattering (QELS)
      measurements have been carried out on sodium taurodeoxycholate (NaTDC) micellar
      aqueous solutions. Computer simulation of the ESR line shape has been used to
      quantitatively analyze the rotational dynamics of the cholestan-spin label (CSL)
      dissolved by the NaTDC micellar aggregates as a function of temperature and NaCl
      concentration. The local reorientation of CSL has been accounted for motionally
      averaged g- and A-tensors assuming fast oscillation around the spin-probe long
      molecular axis. The overall Brownian tumbling of CSL-micelle complexes has been
      modeled by an axially symmetric rotational tensor. Good agreement with
      experimental spectra is obtained. Best-fit rotational parameters and QELS data
      suggest that, in the circumstance of large aggregation, NaTDC micelles have
      cylindrical shape and micellar growth occurs along the cylinder axis.

PMID- 15267341
TI  - Dynamics of supercooled and glassy dipropyleneglycol dibenzoate as functions of
      temperature and aging: Interpretation within the coupling model framework.
AB  - Dielectric relaxation measurements of a typical small molecular glassformer,
      dipropyleneglycol dibenzoate show the presence of two secondary relaxations.
      Their dynamic properties differ in the equilibrium liquid and glassy states, as
      well as the changes during structural recovery after rapid quenching the liquid
      to form a glass. These differences enable us to identify the slower secondary
      relaxation as the genuine Johari-Goldstein (JG) beta-relaxation, acting as the
      precursor of the primary alpha-relaxation. Agreement between the JG beta
      relaxation time and the independent relaxation time of the coupling model leads
      to predicted quantitative relations between the JG beta-relaxation and the alpha
      relaxation that are supported by the experimental data.

PMID- 15267342
TI  - The impact of the multipolar distribution on chiral discrimination in racemates.
AB  - This article explores the impact of the multipolar distribution on chiral
      discrimination in a series of racemic fluids. Discrimination is measured via the
      difference between the like-like (LL) and the like-unlike (LU) radial
      distributions in the liquid. We have found previously that the magnitude and
      orientation of the molecular dipole have a decisive impact on the short-ranged
      enantiomeric imbalance in racemates. Although quadrupolar and octupolar
      interactions decrease more rapidly with intermolecular separation, they can be
      significant at small separations, where enantiomeric imbalances occur. We have
      carefully selected a number of models in which we isolate the effects of the
      molecular quadrupole and octupole. We find that discrimination can be greatly
      enhanced by changes in the quadrupole moments. However, for octupole moments,
      changes in discrimination are small and some octupoles inhibit discrimination. We
      identify the quadrupole moment closest to the plane perpendicular to the
      direction of the molecular dipole as the moment that has the greatest favorable
      effect on chiral discrimination in racemates. In racemates where this moment is
      large, we have found differences of up to 40% between the LL and the LU radial
      distributions.

PMID- 15267343
TI  - Many-body potentials for aqueous Li(+), Na(+), Mg(2+), and Al(3+): comparison of
      effective three-body potentials and polarizable models.
AB  - Many-body potentials for the aqueous Li(+), Na(+), Mg(2+), and Al(3+) ions have
      been constructed from ab initio cluster calculations. Pure pair, effective pair,
      effective three-body, and effective polarizable models were created and used in
      subsequent molecular dynamics simulations. The structures of the first and second
      solvation shells were studied using radial distribution functions and angular
      radial distribution functions. The effective three-body and polarizable
      potentials yield similar first-shell structures, while the contraction of the O-O
      distances between the first and second solvation shells is more pronounced with
      the polarizable potentials. The definition of the tilt angle of the water
      molecules around the ions is discussed. When a proper definition is used, it is
      found that for Li(+), Mg(2+), and Al(3+) the water molecules prefer a trigonal
      orientation, but for Na(+) a tetrahedral orientation (ion in lone-pair direction)
      is preferred. The self-diffusion coefficients for the water molecules and the
      ions were calculated; the ionic values follow the order obtained from experiment,
      although the simulated absolute values are smaller than experiment for Mg(2+) and
      Al(3+).

PMID- 15267344
TI  - Hard sphere perturbation theory for fluids with soft-repulsive-core potentials.
AB  - The thermodynamic properties of fluids with very soft repulsive-core potentials,
      resembling those of some liquid metals, are predicted with unprecedented accuracy
      using a new first-order thermodynamic perturbation theory. This theory is an
      extension of Mansoori-Canfield/Rasaiah-Stell (MCRS) perturbation theory, obtained
      by including a configuration integral correction recently identified by Mon, who
      evaluated it by computer simulation. In this work we derive an analytic
      expression for Mon's correction in terms of the radial distribution function of
      the soft-core fluid, g(0)(r), approximated using Lado's self-consistent extension
      of Weeks-Chandler-Andersen (WCA) theory. Comparisons with WCA and MCRS
      predictions show that our new extended-MCRS theory outperforms other first-order
      theories when applied to fluids with very soft inverse-power potentials (n< or
      =6), and predicts free energies that are within 0.3 kT of simulation results up
      to the fluid freezing point.

PMID- 15267345
TI  - Extended rotational diffusion and orientational relaxation of symmetric top
      molecules in a strong dc electric field: second-rank orientational correlation
      functions.
AB  - Second-rank orientational correlation functions (pertaining to Kerr effect
      relaxation and Raman scattering) are obtained using the extended rotational
      diffusion (J-diffusion) model of symmetric top polar molecules in a strong
      constant external field. It is shown that the shape of the molecule noticeably
      affects all second-rank correlation functions and relaxation times in the rare
      collision limit. In the opposite limit of frequent collisions, the quantities of
      interest are shown to be shape independent as a consequence of vanishingly small
      inertial effects. An interpolation formula for the orientation relaxation times
      in the intermediate regime between the rare and frequent collision limits is also
      given.

PMID- 15267346
TI  - Molecular dynamics simulations of acetonitrile/dimethyl sulfoxide liquid
      mixtures.
AB  - Binary liquid mixtures of dimethyl sulfoxide and acetonitrile at the three molar
      fractions 0.25, 0.50, and 0.75 have been investigated by molecular dynamics
      computer simulations. Thermodynamic states corresponding to liquid-vapor
      coexistence at a temperature of 298 K were considered. Intermolecular
      interactions were described by potential models of the site-site (12-6) Lennard
      Jones plus Coulomb type that have been developed for the description of the pure
      liquids. Dimethyl sulfoxide has been represented by four interactions sites and
      acetonitrile by a three- as well as a six-site potential model. We have
      calculated thermodynamic properties and the intermolecular pair distribution
      functions. Intermolecular interaction energies indicate deviations from the
      behavior of ideal mixtures. The local mole fraction analysis demonstrates that
      dimethyl sulfoxide is preferentially solvated by acetonitrile and that the first
      solvation shell surrounding acetonitrile molecules is significantly enriched by
      dimethyl sulfoxide. The nonideal behavior in the mixtures is not affected by the
      choice of the three- or the six-site potential model for acetonitrile.
      Orientational correlations of dipole vectors within the first solvation shells
      indicate that the relative molecular orientations found in pure acetonitrile and
      dimethyl sulfoxide are maintained in the mixtures. Parallel and antiparallel
      dipole-dipole configurations determine first shell acetonitrile-dimethyl
      sulfoxide configurations. Dynamical features of the mixtures are discussed in
      terms of diffusion constants and orientational correlation times as obtained from
      the time correlation functions for linear velocities and molecular dipole
      moments, respectively. Computed relaxation times indicate faster reorientational
      motion for dimethyl sulfoxide if acetonitrile is added. In contrast, the
      orientational dynamics of acetonitrile becomes stronger correlated upon dilution
      with dimethyl sulfoxide. The diffusion coefficients for both compounds follow
      this tendency.

PMID- 15267347
TI  - Effects of equilibrium H-bond distance and angle changes on Raman intensities
      from water.
AB  - The H-bond energy dispersion over the inhomogeneously broadened OD stretching
      contour from dilute HDO in H(2)O was determined from absolute Raman intensities;
      it displays a large minimum near omega=2440 cm(-1) from short, strong H bonds (in
      agreement with the peak omega from lda ice) and a large maximum near 2650-2675
      cm(-1) due to extremely weak or broken H bonds (in agreement with the peak omega
      from dense, supercritical HDO in H(2)O, 0.9 g/cm(3), 673 K). The difference
      between extrema is the maximum H-bond DeltaE, 5100+/-500 cal/mol, in excellent
      agreement with Pauling's limiting value. A pressure of 1500 bars yields an
      additional maximum and shoulder between the two dispersion extrema from pure
      water; saturated NaCl in water shows the additional maximum. The maxima near 3350
      cm(-1) (1500 bar) or near 3360 cm(-1) (NaCl-H(2)O) arise from bent H bonds; 3350
      cm(-1) (1500 bar) corresponding to an angle of approximately 170 degrees in the
      joint frequency/bend, probability of Lawrence and Skinner. Rising omega refers to
      a higher probability of larger O-O distances, bent H bonds, and H-bond weakening
      and breakage. A approximately 50-80 cm(-1) difference between the 2727 cm(-1) OD
      peak from HDO in steam, and the 2650-2675 cm(-1) dispersion maximum is explained
      via the very broad approximately 60 cm(-1) liquid peak observed at 342 degrees C
      and 2000 bar.

PMID- 15267348
TI  - Molecular dynamics simulations of gas separations using faujasite-type zeolite
      membranes.
AB  - Gas separations with faujasite zeolite membranes have been examined using the
      method of molecular dynamics. Two binary mixtures are investigated,
      oxygen/nitrogen and nitrogen/carbon dioxide. These mixtures have been found
      experimentally to exhibit contrasting behavior. In O(2)/N(2) mixtures the ideal
      selectivity (pure systems) is higher than the mixture selectivity, while in
      N(2)/CO(2) the mixture selectivity is higher than the ideal selectivity. One of
      the key goals of this work was to seek a fundamental molecular level
      understanding of such divergent behavior. Our simulation results (using
      previously developed intermolecular models for both the gases and zeolites
      investigated) were found to replicate this experimental behavior. By examining
      the loading of the membranes and the diffusion rates inside the zeolites, we have
      been able to explain such contrasting behavior of O(2)/N(2) and N(2)/CO(2)
      mixtures. In the case of O(2)/N(2) mixtures, the adsorption and loading of both
      O(2) and N(2) in the membrane are quite competitive, and thus the drop in the
      selectivity in the mixture is primarily the result of oxygen slowing the
      diffusion of nitrogen and nitrogen somewhat increasing the diffusion of oxygen
      when they pass through the zeolite pores. In N(2)/CO(2) systems, CO(2) is rather
      selectively adsorbed and loaded in the zeolite, leaving very little room for N(2)
      adsorption. Thus although N(2) continues to have a higher diffusion rate than
      CO(2) even in the mixture, there are so few N(2) molecules in the zeolite in
      mixtures that the selectivity of the mixture increases significantly compared to
      the ideal (pure system) values. We have also compared simulation results with
      hydrodynamic theories that classify the permeance of membranes to be either due
      to surface diffusion, viscous flow, or Knudsen diffusion. Our results show
      surface diffusion to be the dominant mode, except in the case of N(2)/CO(2)
      binary mixtures where Knudsen diffusion also makes a contribution to N(2)
      transport.

PMID- 15267349
TI  - Functionalization of carbon nanotubes using phenosafranin.
AB  - Spectroscopic analysis and atomic force microscopy (AFM) phase imaging studies
      show self-assembly of phenosafranin (PSF) to multiwalled carbon nanotubes
      (MWNTs). The shift in absorption spectra is associated with charge transfer of
      valence electrons from PSF to electron accepting sites on the MWNTs. The Raman
      active disorder modes are used to fingerprint PSF attachment to MWNTs via defect
      states. AFM phase imaging was used to obtain a molecular topographic visual
      confirmation of PSF attached to the MWNT.

PMID- 15267350
TI  - An ab initio study of structural properties and single vacancy defects in
      Wurtzite AlN.
AB  - The cell parameters, bulk moduli and electronic densities-of-states (DOS) of pure
      and vacancy defect AlN were computed using generalized-gradient approximation
      (GGA) and hybrid functional (B3LYP) computational methods within both plane wave
      pseudopotential and localized Gaussian basis set approaches. All of the methods
      studied yielded cell parameters and bulk moduli in reasonable agreement with
      experiment. The B3LYP functional was also found to predict an optical band gap in
      excellent agreement with experiment. These methods were subsequently applied to
      the calculation of the geometry, defect state positions and formation energies of
      the cation (V(Al)) and anion (V(N)) single vacancy defects. For the V(Al) defect,
      the plane wave-pseudopotential predicted a significant retraction of the
      neighboring N away from the vacancy, while for the V(N) defect, only slight
      relaxations of the surrounding Al atoms towards the vacancy were predicted. For
      the computed DOS of both vacancy defects, the GGA methods yielded similar
      features and defect level positions relative to the valence band maximum, while
      the B3LYP method predicted higher separations between the defect levels and the
      valence and conduction bands, leading to higher energy occupied defect levels.

PMID- 15267351
TI  - Simulating the effect of surfactant structure on bending moduli of monolayers.
AB  - We have used dissipative particle dynamics to simulate amphiphilic monolayers on
      the interface between oil and water. An ultralow interfacial tension is imposed
      by means of Monte Carlo to resemble the amphiphilic films that separate oil and
      water regions in microemulsions. We calculate the bending modulus by analyzing
      the undulation spectrum. By varying the surfactant chain length and topology we
      investigate the effect of surfactant structure and composition of the monolayer
      on the bending moduli. We find that increasing the thickness has a larger effect
      than increasing the density of the layer. This follows from the observations that
      at a given interfacial tension, the bending modulus increases with chain length
      and is larger for linear than branched surfactants. The increase with chain
      length is approximately linear, which is slower than the theoretical predictions
      at a fixed area. We also investigated a binary mixture of short and long
      surfactants compared to pure layers of the same average chain length. We find a
      roughly linear decrease in bending modulus with mole fraction of short
      surfactants. Furthermore, the mixed film has a lower bending modulus than the
      corresponding pure film for all mole fractions. Linking the bending moduli to the
      structure of the surfactants is an important step in predicting the stability of
      microemulsions.

PMID- 15267352
TI  - Adsorption modes of cysteine on Au(111): thiolate, amino-thiolate, disulfide.
AB  - The adsorption of cysteine on the (111) surface of gold has been studied by means
      of periodic supercell density-functional theory calculations. A number of
      different adsorption modes are examined, including adsorption through the thiol
      group in either thiolate or disulfide form, and adsorption through both the thiol
      and amino functional groups. We find that at intermediate coverage densities the
      latter mode of adsorption is favored, followed by thiolate adsorption at the
      bridge (slightly displace toward fcc) site. The N-Au and S-Au bond strengths in
      the amino-thiolate adsorption are estimated to be of the order of 6 and 47
      kcal/mol, respectively. The electronic structure of the different systems is
      analyzed, with focus on the total and projected density of states, as well as on
      the detailed character of the electronic states at the interface. States near the
      Fermi energy are found to have a metal-molecule antibonding character, whereas
      metal-molecule bonding states mostly occur near the lower edge of the Au-d band.

PMID- 15267353
TI  - Sodium diffusion through amorphous silica surfaces: a molecular dynamics study.
AB  - We have studied the diffusion inside the silica network of sodium atoms initially
      located outside the surfaces of an amorphous silica film. We have focused our
      attention on structural and dynamical quantities, and we have found that the
      local environment of the sodium atoms is close to the local environment of the
      sodium atoms inside bulk sodo-silicate glasses obtained by quench. This is in
      agreement with recent experimental results.

PMID- 15267354
TI  - Zero-voltage conductance of short gold nanowires.
AB  - Using the Landauer formula, the conductance of short gold wires is studied. The
      required electronic structure calculations are performed with a self-consistent
      tight-binding method. We consider gold wires of single-atom diameter with a
      variable number (N=1, em leader,5) of atoms. Depending on N, we find considerable
      conductance variations with one conductance quantum being the upper limit. The
      results are confirmed by means of Friedel's sum rule. Tip-shaped clusters are
      used to provide the contact-wire interfaces and the relation between various tip
      structures and the conductance is discussed. Our predictions about the
      conductance variations agree qualitatively with new experimental results.

PMID- 15267355
TI  - Intrusion and extrusion of water in hydrophobic mesopores.
AB  - We present experimental and theoretical results on intrusion-extrusion cycles of
      water in hydrophobic mesoporous materials, characterized by independent
      cylindrical pores. The intrusion, which takes place above the bulk saturation
      pressure, can be well described using a macroscopic capillary model. Once the
      material is saturated with water, extrusion takes place upon reduction of the
      externally applied pressure. Our results for the extrusion pressure can only be
      understood by assuming that the limiting extrusion mechanism is the nucleation of
      a vapor bubble inside the pores. A comparison of calculated and experimental
      nucleation pressures shows that a proper inclusion of line tension effects is
      necessary to account for the observed values of nucleation barriers. Negative
      line tensions of order 10(-11) J m(-1) are found for our system, in reasonable
      agreement with other experimental estimates of this quantity.

PMID- 15267356
TI  - A combined molecular dynamics+quantum mechanics method for investigation of
      dynamic effects on local surface structures.
AB  - A combined molecular dynamics (MD)+quantum mechanics (QM) method for studying
      processes on ionic surfaces is presented. Through the combination of classical MD
      and ab initio embedded-cluster calculations, this method allows the modeling of
      surface processes involving both the structural and dynamic features of the
      substrate, even for large-scale systems. The embedding approach used to link the
      information from the MD simulation to the cluster calculation is presented, and
      rigorous tests have been carried out to ensure the feasibility of the method. The
      electrostatic potential and electron density resulting from our embedded-cluster
      model have been compared with periodic slab results, and confirm the satisfying
      quality of our embedding scheme as well as the importance of applying embedding
      in our combined MD+QM approach. We show that a highly accurate representation of
      the Madelung potential becomes a prerequisite when the embedded-cluster approach
      is applied to temperature-distorted surface snapshots from the MD simulation.

PMID- 15267357
TI  - Effects of wetting and anchoring on capillary phenomena in a confined liquid
      crystal.
AB  - A fluid of hard spherocylinders of length-to-breadth ratio L/D=5 confined between
      two identical planar, parallel walls--forming a pore of slit geometry--has been
      studied using a version of the Onsager density-functional theory. The walls
      impose an exclusion boundary condition over the particle's centers of mass, while
      at the same time favoring a particular anchoring at the walls, either parallel or
      perpendicular to the substrate. We observe the occurrence of a capillary
      transition, i.e., a phase transition associated with the formation of a nematic
      film inside the pore at a chemical potential different from micro(b)-the chemical
      potential at the bulk isotropic-nematic transition. This transition terminates at
      an Ising-type surface critical point. In line with previous studies based on the
      macroscopic Kelvin equation and the mesoscopic Landau-de Gennes approach, our
      microscopic model indicates that the capillary transition is greatly affected by
      the wetting and anchoring properties of the semi-infinite system, i.e., when the
      fluid is in contact with a single wall or, equivalently, the walls are at a very
      large distance. Specifically, in a situation where the walls are preferentially
      wetted by the nematic phase in the semi-infinite system, one has the standard
      scenario with the capillary transition taking place at chemical potentials less
      than micro(b) (capillary nematization transition or capillary ordering
      transition). By contrast, if the walls tend to orientationally disorder the
      fluid, the capillary transition may occur at chemical potentials larger than
      micro(b), in what may be called a capillary isotropization transition or
      capillary disordering transition. Moreover, the anchoring transition that occurs
      in the semi-infinite system may affect very decisively the confinement properties
      of the liquid crystal and the capillary transitions may become considerably more
      complicated.

PMID- 15267358
TI  - Hybridization dynamics of surface immobilized DNA.
AB  - We model the hybridization kinetics of surface attached DNA oligomers with
      solubilized targets. Using both master equation and rate equation formalisms, we
      show that, for surface coverages at which the surface immobilized molecules
      interact, barriers to penetration create a distribution of target molecule
      concentrations within the adsorbed layer. By approximately enumerating probe and
      target conformations, we estimate the probability of overlap between
      complementary probe and target regions as a function of probe density and chain
      length. In agreement with experiments, we find that as probe molecules interact
      more strongly, fewer nucleation sites become accessible and binding rates are
      diminished relative to those in solution. Nucleation sites near the grafted end
      of the probes are least accessible; thus targets which preferentially bind to
      this region show more drastic rate reductions than those that bind near the free
      end of the probe. The implications of these results for DNA-based biosensors are
      discussed.

PMID- 15267359
TI  - Relaxation processes of the liquid crystal ME6N in the isotropic phase studied by
      Raman scattering experiments.
AB  - We have investigated the Raman profiles of the nu(C[Triple Bond]N) and nu(C=O)
      vibrational modes of the nematic liquid crystal ME6N (4-cyanophenyl-4(')
      hexylbenzoate) in the isotropic phase at different temperatures and used them as
      probes of the dynamics and structural organization of this liquid. The
      vibrational time correlation functions of the nu(C[Triple Bond]N) mode, rather
      adequately interpreted within the assumption of exponential modulation function
      (the Kubo-Rothschild theory), indicate that the system experiences an
      intermediate dynamical regime that gets only slightly faster with increasing
      temperature. However, this theory fails in predicting the non-exponential
      behavior that the time correlation functions manifest in the long time range (t>3
      ps). For this reason we have additionally approached the interpretation of
      vibrational correlation functions in terms of the theory formulated by Rothschild
      and co-workers for locally structured liquids. The application of this theory
      reveals that the molecular dynamics in this liquid crystal in the isotropic phase
      is that deriving from a distribution of differently sized clusters, which narrows
      as the temperature increases. Even at the highest temperature reached in this
      study (87 degrees C above the nematic-isotropic transition), the liquid has not
      yet achieved the structure of the simple liquid and the dynamics has not reached
      the limit of the single channel process. The vibrational and orientational
      relaxations occur in very different time scales. The temperature independence of
      the orientational dynamics in the whole range from 55 degrees C to 135 degrees C
      has been referred to the nonhydrodynamic behavior of the system, arising when
      local pseudonematic structures persist for times longer than the orientational
      relaxation. The occurrence of the process of resonant vibrational energy transfer
      between the C=O groups of adjacent molecules has been revealed in the isotropic
      phase by a slightly positive Raman noncoincidence effect in the band associated
      with the nu(C=O) mode. A qualitative interpretation is tentatively given in terms
      of partial cancellation of contributions deriving from structures having opposite
      orientations of their C=O groups.

PMID- 15267360
TI  - Effects of surfactant micelles on viscosity and conductivity of poly(ethylene
      glycol) solutions.
AB  - The neutral polymer-micelle interaction is investigated for various surfactants
      by viscometry and electrical conductometry. In order to exclude the well-known
      necklace scenario, we consider aqueous solutions of low molecular weight
      poly(ethylene glycol) (2-20)x10(3), whose radial size is comparable to or smaller
      than micelles. The single-tail surfactants consist of anionic, cationic, and
      nonionic head groups. It is found that the viscosity of the polymer solution may
      be increased several times by micelles if weak attraction between a polymer
      segment and a surfactant exists, epsilon<k(B)T. Similarly, ion migration in
      polymer solutions may be significantly hindered by cooperative interactions
      between polymers and micelles. Even though epsilon is small, the interaction
      energy between a macromolecule and a micelle can be a few k(B)T due to many
      contacts, and thus leads to polymer adsorption on micelles' surfaces. The rapid
      growth of the viscosity with surfactant concentration is therefore attributed to
      the considerable cross links among micelles and polymers (transient network). In
      addition to substantial alteration of the transport properties, this weak
      interaction also influences the onset point of thermodynamic instability
      associated with polymer-surfactant solutions. The examples include the decrease
      of critical aggregation concentration for ionic surfactant and clouding point for
      nonionic surfactant due to PEG addition.

PMID- 15267361
TI  - Estimation of excess solvation numbers of water and cosolvents from preferential
      interaction and volumetric experiments.
AB  - To elucidate, at a molecular level, how cosolvents influence protein stability,
      it is indispensable to understand the distribution of water and cosolvent
      molecules around proteins. Calculation of excess solvation numbers of water and
      cosolvents serves this purpose, and I show that they can be extracted from
      preferential interaction parameter and volumeric data via the Kirkwood-Buff
      theory. This scheme was applied to trehalose and glycerol (stabilizers) and urea
      (denaturant). Important insights from the application include stabilizer-induced
      enhancement of protein hydration, which, together with the stabilizer's exclusion
      from protein surfaces, may contribute to protein stabilization at high osmolyte
      concentrations.

PMID- 15267362
TI  - Comment on "Comment on 'Constant temperature molecular dynamics simulations by
      means of a stochastic collision model. II. The harmonic oscillator' [J. Chem.
      Phys. 104, 3732 (1996)]" [J. Chem. Phys. 106, 1646 (1997)].
AB  - An argument brought forward by Sholl and Fichthorn against the stochastic
      collision-based constant temperature algorithm for molecular dynamics simulations
      developed by Kast et al. is refuted. It is demonstrated that the large
      temperature fluctuations noted by Sholl and Fichthorn are due to improperly
      chosen initial conditions within their formulation of the algorithm. With the
      original form or by suitable initialization of their variant no deficient
      behavior is observed.

PMID- 15267365
TI  - Electric field-controlled water permeation coupled to ion transport through a
      nanopore.
AB  - We report molecular dynamics simulations of a generic hydrophobic nanopore
      connecting two reservoirs which are initially at different Na(+) concentrations,
      as in a biological cell. The nanopore is impermeable to water under equilibrium
      conditions, but the strong electric field caused by the ionic concentration
      gradient drives water molecules in. The density and structure of water in the
      pore are highly field dependent. In a typical simulation run, we observe a
      succession of cation passages through the pore, characterized by approximately
      bulk mobility. These ion passages reduce the electric field, until the pore
      empties of water and closes to further ion transport, thus providing a possible
      mechanism for biological ion channel gating.

PMID- 15267366
TI  - Multireference spin-adapted variant of density functional theory.
AB  - A new Kohn-Sham formalism is developed for studying the lowest molecular
      electronic states of given space and spin symmetry whose densities are
      represented by weighted sums of several reference configurations. Unlike standard
      spin-density functional theory, the new formalism uses total spin conserving spin
      density operators and spin-invariant density matrices so that the method is fully
      spin-adapted and solves the so-called spin-symmetry dilemma. The formalism
      permits the use of an arbitrary set of reference (noninteracting) configurations
      with any number of open shells. It is shown that the requirement of degeneracy of
      the total noninteracting energies of the reference configurations (or
      configuration state functions) is equivalent to the stationary condition of the
      exact energy relative to the weights of the configurations (or configuration
      state functions). Consequently, at any molecular geometry, the weights can be
      determined by minimization of the energy, and, for given reference weights, the
      Kohn-Sham orbitals can be determined. From this viewpoint, the developed theory
      can be interpreted as an analog of the multiconfiguration self-consistent field
      approach within density functional theory.

PMID- 15267367
TI  - Block-correlated coupled cluster theory: the general formulation and its
      application to the antiferromagnetic Heisenberg model.
AB  - The general formalism of the block-correlated coupled cluster (BCCC) method, an
      alternative multireference coupled cluster method for calculating the ground
      state electronic structures of molecular systems, has been presented. The BCCC
      theory is constructed in terms of a complete set of many-electron states of
      individual blocks, assumed that the whole system could be partitioned into a set
      of blocks. The reference state in the BCCC is selected as a tensor product of the
      most important many-electron state of each system block. By truncating the
      cluster operator to a certain n-block correlation level, an approximate but size
      extensive BCCC method, denoted as BCCCn, is defined. For reducing the
      computational effort but without much loss of accuracy, the reduced density
      matrix is introduced to generate an optimal subset of many-electron states for
      each block. I have implemented the BCCCn (n=2,3) methods within the S=1/2
      Heisenberg Hamiltonian, and applied them to calculate the ground-state energies
      of one-dimensional spin chains and quasi-one-dimensional two-leg spin ladders.
      The calculated results show that with the appropriate partition of the studied
      systems the BCCC3 method can yield quite satisfactory ground-state energies for
      these spin systems.

PMID- 15267368
TI  - Density-functional theory calculations of optical rotatory dispersion in the
      nonresonant and resonant frequency regions.
AB  - The complex linear response function, which can be employed for calculations of
      second-order molecular properties in regions of strong absorption, is here
      extended to encompass the mixed electric-dipole-magnetic-dipole polarizability.
      The mixed electric-dipole-magnetic-dipole polarizability determines the optical
      rotation and, when absorption is taken into account, the full anomalous optical
      rotatory dispersion (ORD) spectra of chiral molecules can be calculated using
      first-principle quantum-chemical methods. Gauge-origin independence of the
      results is ensured through the use of London atomic orbitals. To illustrate the
      importance of taking the absorption process properly into account, we here apply
      this methodology to the study of the anomalous ORD of hydrogen peroxide, 3R
      methylcyclohexanone, 4R-1,1-dimethyl-[3]-(1,2)-ferrocenophan-2-on, and the D(2)
      isomer of the C(84) fullerene.

PMID- 15267369
TI  - Simple and accurate method to evaluate tunneling splitting in polyatomic
      molecules.
AB  - A practical and accurate semiclassical method for calculating the tunneling
      splitting of the ground state in polyatomic molecules is presented based on a
      recent version of the instanton theory [J. Chem. Phys. 115, 6881 (2001)]. The
      method uses ab initio quantum chemical data for the potential energy surface
      without any concomitant extrapolation and requires only a small number of ab
      initio data points to get convergence even for large molecules. This enables one
      to use an advanced level of electronic structure theory and achieve a high
      accuracy of the result. The method is applied to the 9-atomic malonaldehyde
      molecule by making use of the potential energy surface at the level of CCSD(T)
      with the hybrid basis set of aug-cc-pVTZ (for oxygen atoms and the transferred
      hydrogen atom) and cc-pVTZ (for other atoms).

PMID- 15267370
TI  - Energy partitioning for "fuzzy" atoms.
AB  - The total energy of a molecule is presented as a sum of one- and two-atomic
      energy components in terms of "fuzzy" atoms, i.e., such divisions of the three
      dimensional physical space into atomic regions in which the regions assigned to
      the individual atoms have no sharp boundaries but exhibit a continuous transition
      from one to another. By proper definitions the energy components are on the
      chemical energy scale. The method is realized by using Becke's integration scheme
      and weight function permitting very effective numerical integrations.

PMID- 15267371
TI  - Decoupling quantum dissipation interaction via stochastic fields.
AB  - Based on the Hubbard-Stratonovich transformation, the dissipative interaction
      between the system of interest and the heat bath is decoupled and the separated
      system and bath thus evolve in common classical random fields. This manipulation
      allows us to establish a novel theoretical methodology by which the reduced
      density matrix is formulated as an ensemble average of its random realizations in
      the auxiliary white noise fields. Within the stochastic description, the
      interaction between the system and the bath is reflected in the mutually induced
      mean fields. The relationship between the bath-induced field and the influence
      functional in the path integral framework is revealed. As a demonstration of this
      approach, we derive the exact master equations for two model systems.

PMID- 15267372
TI  - Mass analyzed threshold ionization spectroscopy of 5-methylindole and 3
      methylindole cations and the methyl substitution effect.
AB  - The vibrationally resolved mass analyzed threshold ionization spectra of
      jetcooled 5-methylindole (5MI) and 3-methylindole (3MI) have been recorded by
      ionizing via various vibronic levels of each species. The adiabatic ionization
      energies (IEs) of 5MI and 3MI are determined to be 61,696+/-5 and 60,679+/-5 cm(
      1), which are less than that of indole by 895 and 1912 cm(-1), respectively.
      Comparing these data with those of 1-methylindole and indole suggests that the
      methyl substitution on the pyrrole part leads to a greater redshift in the IE
      than on the benzene part. These experimental findings are well supported by the
      theoretical calculations. Analysis on these new data shows that many active
      vibrations of the 5MI cation are related to the CH(3) torsion and in-plane ring
      bending vibrations. In contrast, the observed vibrational bands of the 3MI cation
      are very weak due to unfavorable Franck-Condon transition.

PMID- 15267373
TI  - Quantum solvation of phthalocyanine in superfluid helium droplets.
AB  - We have measured quantum states of the solvent-solute system of phthalocyanine in
      superfluid helium droplets in a high resolution pump-probe experiment. This
      provides evidence for the attribution of a splitting effect in the emission
      spectra of phthalocyanine in helium droplets to the relaxation of the first
      helium layer upon electronic excitation, measured recently by us. Our
      experimental results are a strong indication for the first helium layer playing a
      key roll for the solvation of molecules in helium droplets and, thus, for their
      spectroscopic features.

PMID- 15267375
TI  - An ab initio study of the competing reaction channels in the reaction of HOCO
      radicals with NO and O2.
AB  - The reaction between HOCO and NO, and that between HOCO and O(2), have been
      examined using the quadratic configuration interaction method to locate and
      optimize the critical points on the potential energy surfaces. Analysis of the
      critical points provides new insight into new intermediates and pathways by which
      these reactions occur and help explain recent experimental results. In the
      HOCO+O(2) reaction, the symmetry-allowed products, CO(2)+HO(2), can be obtained
      both via direct hydrogen abstraction by O(2) on the HCO radicals, as well as
      through an adduct, HOC(O)O(2), which can proceed to give the same products. The
      less-than-unity yield of CO(2) observed in the experimental studies of the
      HOCO+NO reaction, as well as the lack of CO, can be explained by the formation of
      a stable HOC(O)NO adduct.

PMID- 15267374
TI  - Photophysics of protoporphyrin ions in vacuo: triplet-state lifetimes and quantum
      yields.
AB  - Lifetimes of triplet-state molecules and triplet quantum yields are important
      parameters in photobiology as they determine the generation of singlet-oxygen
      upon irradiation with visible light. Here we report lifetimes of protoporphyrin
      IX (pp) in vacuo measured in an ion storage ring. We find that after 532 nm
      photon absorption, pp(-) (free base and negatively charged carboxylate) and pp(+)
      (single protonation of ring nitrogen) have triplet-state lifetimes of 12 and 6
      ms, respectively. After 415 or 390 nm absorption the lifetime of the anion is
      shorter (1.5 and 0.6 ms) as expected from the increase in temperature. Triplet
      quantum yields of pp(-) and pp(+) are similar, 0.6-0.7, close to values reported
      for the free base and monocation in solution. The other channel, direct decay to
      the electronic ground state and subsequent dissociation of vibrationally excited
      ions, is much faster than triplet-singlet intersystem crossing. We measured
      lifetimes of 63 micros, 96 micros, and 0.3 ms after 390, 415, and 532 nm
      excitation, respectively. A fit of a statistical model to the pp(-) decay results
      in an Arrhenius activation energy of 0.5+/-0.2 eV for CO(2) loss and a low
      preexponential factor (10(6)-10(10) s(-1)), indicative of an entropic barrier.

PMID- 15267376
TI  - First principles study of the stability and electronic structure of the
      icosahedral La13, La(-1) (13), and La(+1) (13) clusters.
AB  - The structural stability and electronic-structure of icosahedral La(13), La(-1)
      (13), and La(+1) (13) clusters have been studied by DMOL cluster method based on
      density-functional theory. The ground state of all-electron with relativity
      results is shown to be a distorted D(2h) icosahedron by the Jahn-Teller effect.
      However, the binding energies of D(3d) and D(5d) are very close to that of the
      D(2h) structure for La(13), La(-1) (13), and La(+1) (13) clusters. The effective
      core potential results show that the true ground state is D(5d) structure. The
      clusters have small magnetic moments and the symmetry of cluster is an important
      factor in determining the magnetic moments of the clusters. The effects of
      interatomic spacing and coordination on atomic magnetic moment are discussed.
      Further, 5d electrons dominate the hybrid orbitals below the Fermi level in the
      neutral cluster and contribute the main spin of clusters.

PMID- 15267377
TI  - Internal state distributions of fragment HCO via S0 and T1 pathways of glyoxal
      after photolysis in the ultraviolet region.
AB  - The dynamics of photodissociation of glyoxal (HOC-COH) near the dissociation
      threshold on the triplet manifold are studied through measurement of
      distributions of nascent fragment HCO in various internal states. Three
      rotational levels 1(01) (*), 4(13) (*), and 3(21) (*)+3(22) (*) of vibrational
      state U (excitation wavelength approximately 394.4 nm, origin at 25,331.865 cm(
      1)) of glyoxal in state A (1)A(u) and two other vibrational states at excitation
      wavelengths 390.33 and 382.65 nm are selected to produce fragment HCO. By means
      of fluorescence in the transition B (2)A(')-X (2)A(') of HCO, we determined the
      relative populations of internal states of that fragment. Rotational states of
      product HCO up to N=26 and K=2 are populated, and bimodal distributions of these
      rotational states are observed for the photolysis wavelengths used in this work.
      The high rotational part of the distribution with average energy near values
      calculated on the basis of the statistical model-phase-space theory is assigned
      to arise from glyoxal on its S(0) surface, and the low rotational part from the
      T(1) surface with an exit barrier. After photolysis near the threshold region on
      the triplet surface, HCO arising from the T(1) state appears to be a major
      component of products because these rotational levels 1(01) (*), 4(13) (*), and
      3(2) (*) of U state selected are gateway states with an enhanced rate of
      intersystem crossing.

PMID- 15267378
TI  - Comparing the dynamical effects of symmetric and antisymmetric stretch excitation
      of methane in the Cl+CH4 reaction.
AB  - The effects of two nearly isoenergetic C-H stretching motions on the gas-phase
      reaction of atomic chlorine with methane are examined. First, a 1:4:9 mixture of
      Cl(2), CH(4), and He is coexpanded into a vacuum chamber. Then, either the
      antisymmetric stretch (nu(3)=3019 cm(-1)) of CH(4) is prepared by direct infrared
      absorption or the infrared-inactive symmetric stretch (nu(1)=2917 cm(-1)) of
      CH(4) is prepared by stimulated Raman pumping. Photolysis of Cl(2) at 355 nm
      generates fast Cl atoms that initiate the reaction with a collision energy of
      1290+/-175 cm(-1) (0.16+/-0.02 eV). Finally, the nascent HCl or CH(3) products
      are detected state-specifically via resonance enhanced multiphoton ionization and
      separated by mass in a time-of-flight spectrometer. We find that the
      rovibrational distributions and state-selected differential cross sections of the
      HCl and CH(3) products from the two vibrationally excited reactions are nearly
      indistinguishable. Although Yoon et al. [J. Chem. Phys. 119, 9568 (2003)] report
      that the reactivities of these two different types of vibrational excitation are
      quite different, the present results indicate that the reactions of symmetric
      stretch excited or antisymmetric-stretch excited methane with atomic chlorine
      follow closely related product pathways. Approximately 37% of the reaction
      products are formed in HCl(v=1,J) states with little rotational excitation. At
      low J states these products are sharply forward scattered, but become almost
      equally forward and backward scattered at higher J states. The remaining reaction
      products are formed in HCl(v=0,J) and have more rotational excitation. The
      HCl(v=0,J) products are predominantly back and side scattered. Measurements of
      the CH(3) products indicate production of a non-negligible amount of umbrella
      bend excited methyl radicals primarily in coincidence with the HCl(v=0,J)
      products. The data are consistent with a model in which the impact parameter
      governs the scattering dynamics.

PMID- 15267379
TI  - Ground state, growth, and electronic properties of small lanthanum clusters.
AB  - The DMol cluster method based on density-functional theory has been employed to
      study the structural stability and electronic structure of La(n) (n=2-14)
      clusters. The ground states have been found out for lanthanum clusters. The Jahn
      Teller effect plays an important role in this process because there are many
      isomers near the ground state. The magnetism is not sensitive to interatomic
      spacing when the change of interatomic spacing is in a small range. Lanthanum
      clusters grow in an icosahedral pattern. The results of the mean binding energy,
      of the second derivative of binding energy, and of the formation energy show
      strong odd-even alternation and that 7- and 13-atom clusters are magic. Further,
      the HOMO-LUMO gap, the mean nearest bond lengths, and the mean magnetic moments
      suggest that the convergence to bulk is slow and it shows an oscillatory behavior
      for small lanthanum clusters.

PMID- 15267380
TI  - Submillimeter-wave spectra of hypoiodous acid.
AB  - Pure rotational spectra of hypoiodous acid, HOI, and its deuterated species, DOI,
      were measured in the frequency range of 320-670 GHz. The molecule was efficiently
      produced by a reaction of atomic oxygen with iodoethane. Rotational constants and
      centrifugal distortion constants for the molecule were determined accurately. The
      vibrationally averaged structure for HOI was obtained by taking the isotopic
      difference of the OH bond length into consideration: r(z)(OH)=0.967(8) A,
      r(z)(OI)=1.9941(3) A, and theta(z)(HOI)=103.89 degrees, where the errors were
      estimated from the residual inertial defect. Equilibrium bond lengths for the OH
      and OI bonds were derived as 0.959(8) A and 1.9874(3) A, respectively, by
      assuming anharmonic constants of the corresponding diatomic molecules. Electric
      quadrupole interaction constants and nuclear-spin-rotation coupling constants for
      the iodine nucleus were obtained. Nonaxial terms of the electric-quadrupole
      constant for HOI can be determined as well, which enabled us to derive the
      principal values of the coupling tensor. The values obtained were used to gauge
      the ionicity of the X-O bond in the HOX molecular system. The nuclear-spin
      rotation coupling constant along the a inertial axis is found to be significantly
      smaller than others, which may be explained by a contribution from two low-lying
      singlet excited states.

PMID- 15267381
TI  - Selective photochemistry via adiabatic passage: degenerate product states with
      different lifetimes.
AB  - Two-pulse selective photochemistry that exploits population transfer via
      adiabatic passage is considered for the case that there are degenerate product
      states with different lifetimes. As an example, a four-level model system with a
      complex symmetric Hamiltonian is constructed. Analytical and numerical studies of
      this model system demonstrate that extensive control over the product branching
      ratio can be achieved by detuning either the pump pulse or the Stokes pulse while
      maintaining negligible population in the intermediate state. This control
      approach represents a significant simplification of both the Kobrak-Rice extended
      stimulated Raman adiabatic passage scheme and the Chen-Shapiro-Brumer strong
      field control scheme.

PMID- 15267382
TI  - Stability and structure of Li(n)H molecules (n=3-6): experimental and density
      functional study.
AB  - The molecules Li(3)H and Li(4)H have been identified in mass-spectrometric
      measurements over solutions of hydrogen in liquid Li, and the gaseous equilibria
      of the reactions: Li(3)H+Li=Li(2)H+Li(2), Li(3)H+Li(2)=Li(2)H+Li(3),
      Li(3)H+Li=LiH+Li(3), Li(3)H+LiH=2Li(2)H, and Li(4)H+Li(2)=Li(3)H+Li(3) have been
      measured. Density functional calculations of Li(n)H molecules (n=3-6) provide
      structures, vibrational frequencies, ionization energies, and free energy
      functions of these molecules, and these are used to estimate the enthalpies of
      these reactions and the atomization energies of Li(3)H (119.4 kcal/mol) and
      Li(4)H (151.8 kcal/mol).

PMID- 15267383
TI  - Excitations, optical absorption spectra, and optical excitonic gaps of
      heterofullerenes. I. C60, C59N+, and C48N12: theory and experiment.
AB  - Low-energy excitations and optical absorption spectrum of C(60) are computed by
      using time-dependent (TD) Hartree-Fock, TD-density functional theory (TD-DFT), TD
      DFT-based tight-binding (TD-DFT-TB), and a semiempirical Zerner intermediate
      neglect of diatomic differential overlap method. A detailed comparison of
      experiment and theory for the excitation energies, optical gap, and absorption
      spectrum of C(60) is presented. It is found that electron correlations and
      correlation of excitations play important roles in accurately assigning the
      spectral features of C(60), and that the TD-DFT method with nonhybrid functionals
      or a local spin density approximation leads to more accurate excitation energies
      than with hybrid functionals. The level of agreement between theory and
      experiment for C(60) justifies similar calculations of the excitations and
      optical absorption spectrum of a monomeric azafullerene cation C(59)N(+), to
      serve as a spectroscopy reference for the characterization of carborane anion
      salts. Although it is an isoelectronic analogue to C(60), C(59)N(+) exhibits
      distinguishing spectral features different from C(60): (1) the first singlet is
      dipole-allowed and the optical gap is redshifted by 1.44 eV; (2) several weaker
      absorption maxima occur in the visible region; (3) the transient triplet-triplet
      absorption at 1.60 eV (775 nm) is much broader and the decay of the triplet state
      is much faster. The calculated spectra of C(59)N(+) characterize and explain well
      the measured ultraviolet-visible (UV-vis) and transient absorption spectra of the
      carborane anion salt [C(59)N][Ag(CB(11)H(6)Cl(6))(2)] [Kim et al., J. Am. Chem.
      Soc. 125, 4024 (2003)]. For the most stable isomer of C(48)N(12), we predict that
      the first singlet is dipole-allowed, the optical gap is redshifted by 1.22 eV
      relative to that of C(60), and optical absorption maxima occur at 585, 528, 443,
      363, 340, 314, and 303 nm. We point out that the characterization of the UV-vis
      and transient absorption spectra of C(48)N(12) isomers is helpful in
      distinguishing the isomer structures required for applications in molecular
      electronics. For C(59)N(+) and C(48)N(12) as well as C(60), TD-DFT-TB yields
      reasonable agreement with TD-DFT calculations at a highly reduced cost. Our study
      suggests that C(60), C(59)N(+), and C(48)N(12), which differ in their optical
      gaps, have potential applications in polymer science, biology, and medicine as
      single-molecule fluorescent probes, in photovoltaics as the n-type emitter and/or
      p-type base of a p-n junction solar cell, and in nanoelectronics as fluorescence
      based sensors and switches.

PMID- 15267384
TI  - Effects of solvation and core switching on the photoelectron angular
      distributions from (CO2)n(-) and (CO2)(n)(-).H2O.
AB  - Photoelectron images are recorded in the photodetachment of two series of cluster
      anions, (CO(2))(n)(-), n=4-9 and (CO(2))(n)(-).H(2)O, n=2-7, with linearly
      polarized 400 nm light. The energetics of the observed photodetachment bands
      compare well with previous studies, showing evidence for switching between two
      anionic core structures: The CO(2)(-) monomer and covalent (CO(2))(2)(-) dimer
      anions. The systematic study of photoelectron angular distributions (PADs) sheds
      light on the electronic structure of the different core anions and indicates that
      solvation by several CO(2) molecules and/or one water molecule has only moderate
      effect on the excess-electron orbitals. The observed PAD character is reconciled
      with the symmetry properties of the parent molecular orbitals. The most
      intriguing result concerns the PADs showing remarkable similarities between the
      monomer and dimer anion cluster-core types. This observation is explained by
      treating the highest-occupied molecular orbital of the covalent dimer anion as a
      linear combination of two spatially separated monomeric orbitals.

PMID- 15267385
TI  - Electronic spectroscopy and ionization potential of UO2 in the gas phase.
AB  - The electronic spectroscopy of UO(2) has been examined using multiphoton
      ionization with mass-selected detection of the UO(2) (+) ions. Supersonic jet
      cooling was used to reduce the spectral congestion. Twenty-two vibronic bands of
      neutral UO(2) were observed in the range from 17,400 to 32,000 cm(-1). These
      bands originated from the U(5fphi(u)7ssigma(g))O(2) X (3)Phi(2u) and (3)Phi(3u)
      states. The stronger band systems are attributed to metal-centered 7p<--7s
      transitions. Threshold ionization measurements were used to determine the
      ionization potentials of UO and UO(2). These were found to be higher than the
      values obtained previously from electron impact measurements but in agreement
      with the results of recent theoretical calculations.

PMID- 15267386
TI  - How much can an intermediate state influence competing reactive pathways?
AB  - A molecule undergoing reaction may form a short-lived intermediate. Under certain
      conditions, the rate at which the reaction proceeds toward the product state via
      the intermediate may exceed that of a simple, direct path. The competition of two
      alternative reactive pathways is analyzed here in terms of a stochastic model.
      The approach allows one to diagnose this competition as a function of the energy
      of the intermediate relative to the barrier heights of the potential surface and
      values of the reactive vibrational modes. The result has applications to a
      variety of problems in chemical physics, ranging from the "lock-and-key"
      mechanism for the enzymatic activity to control of temporal evolution of complex
      systems by optimal laser fields.

PMID- 15267387
TI  - A study of the reactions of molecular hydrogen with small gold clusters.
AB  - This work presents a study of reactions between neutral and negatively charged
      Au(n) clusters (n=2,3) and molecular hydrogen. The binding energies of the first
      and second hydrogen molecule to the gold clusters were determined using density
      functional theory (DFT), second order perturbation theory (MP2) and coupled
      cluster (CCSD(T)) methods. It is found that molecular hydrogen easily binds to
      neutral Au(2) and Au(3) clusters with binding energies of 0.55 eV and 0.71 eV,
      respectively. The barriers to H(2) dissociation on these clusters with respect to
      Au(n)H(2) complexes are 1.10 eV and 0.59 eV for n=2 and 3. Although negatively
      charged Au(n) (-) clusters do not bind molecular hydrogen, H(2) dissociation can
      occur with energy barriers of 0.93 eV for Au(2) (-) and 1.39 eV for Au(3) (-).
      The energies of the Au(2)H(2) (-) and Au(3)H(2) (-) complexes with dissociated
      hydrogen molecules are lower than the energies of Au(2) (-)+H(2) and Au(3) (
      )+H(2) by 0.49 eV and 0.96 eV, respectively. There is satisfactory agreement
      between the DFT and CCSD(T) results for binding energies, but the agreement is
      not as good for barrier heights.

PMID- 15267388
TI  - Quantum control of molecular orientation by two-color laser fields.
AB  - We demonstrate molecular orientation by using phase-controlled two-color
      omega+2omega laser pulses with an intensity of 1.0x10(12) W/cm(2) and a pulse
      duration of 130 fs. The orientation of three iodine-containing molecules (IBr,
      CH(3)I, and C(3)H(5)I) was monitored by the directional asymmetries of the
      photofragment angular distribution in dissociative ionization. In all three
      molecules, the directional asymmetry showed an oscillating behavior dependent on
      the relative phase difference between omega and 2omega pulses. The phase
      dependence of the directional asymmetry observed in iodine ions and counterpart
      ions were out of phase with each other. This result shows that a phase-controlled
      omega+2omega optical field discriminates between parallel and antiparallel
      configurations of aligned molecules that have a permanent dipole. This method
      performed well because (1) molecular orientation can be achieved by all-optical
      fields; (2) the direction of orientation is easily switched by changing the sign
      of the quantum interference; and (3) this method is free from any resonance
      constraint and thus can be applied to any molecule.

PMID- 15267389
TI  - Ab initio potential energy surface, variational transition state theory, and
      quasiclassical trajectory studies of the F+CH4-->HF+CH3 reaction.
AB  - In this work we present a study of the F+CH(4)-->HF+CH(3) reaction
      (DeltaHdegrees(298 K)=-32.0 kcal mol(-1)) using different methods of the chemical
      reaction theory. The ground potential energy surface (PES) is characterized using
      several ab initio methods. Full-dimensional rate constants have been calculated
      employing the variational transition state theory and using directly ab initio
      data. A triatomic analytical representation of the ground PES was derived from ab
      initio points calculated at the second- and fourth-order Moller-Plesset levels
      with the 6-311+G(2df,2pd) basis set, assuming the CH(3) fragment to be a 15
      a.m.u. pseudoatom in the fitting process. This is suggested from experiments that
      indicate that the methyl group is uncoupled to the reaction coordinate. A
      dynamics study by means of the quasiclassical trajectory (QCT) method and
      employing this analytical surface was also carried out. The experimental data
      available on the HF internal states distributions are reproduced by the QCT
      results. Very recent experimental information about the reaction stereodynamics
      is also borne out by our QCT calculations. Comparisons with the benchmark F+H(2)
      and analogous Cl+CH(4) reactions are established throughout.

PMID- 15267390
TI  - A first principles simulation of rigid water.
AB  - We present the results of Car-Parrinello (CP) simulations of water at ambient
      conditions and under pressure, using a rigid molecule approximation. Throughout
      our calculations, water molecules were maintained at a fixed intramolecular
      geometry corresponding to the average structure obtained in fully unconstrained
      simulations. This allows us to use larger time steps than those adopted in
      ordinary CP simulations of water, and thus to access longer time scales. In the
      absence of chemical reactions or dissociation effects, these calculations open
      the way to ab initio simulations of aqueous solutions that require time scales
      substantially longer than presently feasible (e.g., simulations of hydrophobic
      solvation). Our results show that structural properties and diffusion
      coefficients obtained with a rigid model are in better agreement with experiment
      than those determined with fully flexible simulations. Possible reasons
      responsible for this improved agreement are discussed.

PMID- 15267391
TI  - The lattice and rotational dynamics of the methyl halides described by pair
      potentials based on universal force fields.
AB  - A systematical computational study of the lattice and rotational dynamics of the
      methyl halides, which belong to the most simple organic molecules containing
      CH(3) groups, was done. Because of their simplicity there might be a chance to
      understand and model the dynamics of these systems by combining nonbonded pair
      interactions and crystallographic information. Based on the experimentally
      determined crystal structure, which was not relaxed during the calculations,
      interactions were modeled using the transferable parameters of the universal
      force fields. The lattice dynamical calculation can reproduce with reasonable
      accuracy the low-energy regime of the lattice excitations as well as the single
      particle rotational potential of the CH(3) group of the respective halide.

PMID- 15267392
TI  - Lattice gas 2D/3D equilibria: chemical potentials and adsorption isotherms with
      correct critical points.
AB  - A priori information is used to derive the chemical potential as a function of
      density and temperature for 2D and 3D lattice systems. The functional form of
      this equation of state is general in terms of lattice type and dimensionality,
      though it contains critical temperature and critical density as parameters which
      depend on lattice type and dimensionality. The adsorption isotherm is derived
      from equilibrium between two-dimensional and three-dimensional phases.
      Theoretical predictions are in excellent agreement with grand canonical Monte
      Carlo simulations.

PMID- 15267393
TI  - Structure and dynamics of orientational defects in ice I.
AB  - Orientational defects in hexagonal ice were investigated using molecular dynamics
      simulations. Energy relaxation during L- and D-defect migration was shown to be
      associated with improved alignment of water molecules along the local electric
      fields. Two new forms of defects, an "L+D complex," and a "5+7 defect," were
      characterized. These forms appear in ice trajectories close to the melting point,
      and in the course of L- and D-pair recombination process. Defect pair
      recombination was shown to be a complex process, involving collective H-bond
      changes in groups of molecules.

PMID- 15267394
TI  - On the use of the quasi-Gaussian entropy theory in the study of simulated dilute
      solutions.
AB  - In a recent paper [M. D'Alessandro, M. D'Abramo, G. Brancato, A. Di Nola, and A.
      Amadei, J. Phys. Chem. B 106, 11843 (2002)] we showed how to combine molecular
      dynamics simulations with the quasi-Gaussian entropy theory, in order to model
      the statistical mechanics and thermodynamics of ionic (water) solutions. In this
      paper we extend the method to treat nonspherical solutes, describe more
      thoroughly its theoretical basis and apply it to a set of more complex solute
      molecules in water (i.e., water, methane, ethane, methanol, and ethanol). Results
      show that this approach can really provide an excellent theoretical description
      of solute-solvent systems over a wide range of temperatures.

PMID- 15267395
TI  - Nature of long-range correlations of density fluctuations in glass-forming
      liquids.
AB  - Based on a concise review of the experimental data, a theory of the structural,
      kinetic, and dynamic features of the Fischer cluster is put forward. This theory
      is based on the idea of heterophase fluctuations of glass-forming liquids.
      According to these ideas in a one-component liquid the solidlike and fluidlike
      transient associations of molecules (fluctuons) are formed. The fluctuons differ
      in the short-range order and, consequently, in the free energy. They form a
      random free energy landscape. The random field free energy functional of the
      Ginzburg-Landau type, which accounts for the free energy landscape, is deduced.
      Based on this, the phase equilibrium, critical behavior, and ordering phenomena
      of the heterophase liquid are considered. It is shown that in the critical region
      an effective attractive interaction of the fluctuons results in their gravitation
      and formation of correlated fractal aggregations. The aggregation consists of the
      fluctuons of similar short-range order. The fractal aggregation formation is a
      special structural state of the liquid above the glass transition temperature.
      The condition at which the aggregations are formed is formulated. Thus it is
      shown that the Fischer cluster is an array of fractal aggregations of fluctuons.
      The growth kinetics and dynamics of the Fischer cluster are described. The
      experimental data are analyzed and discussed using the theory that is put
      forward.

PMID- 15267396
TI  - Covariance nuclear magnetic resonance spectroscopy.
AB  - Covariance nuclear magnetic resonance (NMR) spectroscopy is introduced, which is
      a new scheme for establishing nuclear spin correlations from NMR experiments. In
      this method correlated spin dynamics is directly displayed in terms of a
      covariance matrix of a series of one-dimensional (1D) spectra. In contrast to two
      dimensional (2D) Fourier transform NMR, in a covariance spectrum the spectral
      resolution along the indirect dimension is determined by the favorable spectral
      resolution obtainable along the detection dimension, thereby reducing the time
      consuming sampling requirement along the indirect dimension. The covariance
      method neither involves a second Fourier transformation nor does it require
      separate phase correction or apodization along the indirect dimension. The new
      scheme is demonstrated for cross-relaxation (NOESY) and J-coupling based
      magnetization transfer (TOCSY) experiments.

PMID- 15267397
TI  - Molecular dynamics simulations of the Ag+ or Na+ cation with an excess electron
      in bulk water.
AB  - The properties of an excess electron interacting with a monovalent cation in bulk
      water are studied by molecular dynamics simulations. Sodium and silver cations
      are chosen as prototypical cases because of their very different redox
      properties. In both cases, mixed quantum classical molecular dynamics simulations
      reproduce the experimental UV-Vis spectra. In the case of silver, we observe a
      highly polarized neutral atom, corresponding to a dipolar excitonic state. For
      sodium a contact cation/electron pair is observed. Free energy curves along the
      cation electron coordinate are calculated using quantum Umbrella Sampling
      technique. The relative stability of the different chemical species is discussed.

PMID- 15267398
TI  - Coherent interactions in femtosecond transient grating.
AB  - Transient grating of a dye in liquid has been measured as a function of the
      electronic coherence period. A diffractive beam splitter and a pair of wedge
      prisms are implemented to achieve precise spatial phase overlap and
      interferometrically accurate control of the time delay between the pump pulses.
      As the electronic coherence period is varied, coherent interactions lead to an
      enhancement or loss of the sharp feature in the transient grating signal near
      time zero, which is usually called coherent spike. Sensitivity of the transient
      grating signal to the solvation process also changes by the coherence time delay.
      All the features can be accounted for by invoking third-order nonlinear response
      functions. Numerical simulations have been performed to corroborate our
      description. This work identifies a major source of the coherent spike in the
      transient grating and transient absorption experiments. In addition, it allows us
      to propose a method that measures the solvation function more efficiently than
      conventional transient grating technique does.

PMID- 15267399
TI  - Degenerate two-photon-absorption spectral studies of highly two-photon active
      organic chromophores.
AB  - Degenerate two-photon absorption (TPA) spectral properties of five AFX
      chromophore solutions have been studied using a single and spectrally dispersed
      sub-picosecond white-light continuum beam. In a specially designed optical
      configuration, optical pathways inside the sample solution for different spectral
      components of the focused continuum beam were spatially separated from each
      other. Thus, the nondegenerate TPA processes coming from different spectral
      components can be eliminated, and the direct nonlinear absorption spectrum
      attributed to degenerate TPA processes can be readily obtained. Using this new
      technique, the complete TPA spectra for these five highly two-photon-active
      compounds (AF-380, AF-350, AF-295, AF-270, and AF-50) were obtained in the
      spectral range from 600 to 950 nm on an absolute scale of TPA cross section. The
      relationship between the molecular structures and their TPA spectral behaviors
      are discussed. In general the measured TPA spectra are not identical with the
      linear absorption spectra on the scale of absorbed photon(s) energy. Moreover,
      for some sample (such as AF-380), the TPA spectrum is totally different from the
      linear spectrum, which implies the difference of molecular transition pathways
      and selection rules for one- and two-photon excitation processes. At high
      excitation intensity levels (>or=15 GW/cm(2)), the saturation behavior of TPA
      transition can be observed obviously in AF-350 and AF-380 solutions that exhibit
      much higher nonlinear absorptivity than the other chromophores investigated.

PMID- 15267400
TI  - A trimer model for water.
AB  - A statistical model for water is studied, where the molecules are represented by
      trimers in a triangular lattice. Each atom of a water molecule occupies a single
      site on the lattice, and the HOH bond angle is assumed to be 120 degrees. The
      molecules can interact via three different potentials: the excluded volume
      interaction, which prevents two molecules from occupying the same atom site, an
      attractive potential between any two nearest-neighbor atoms belonging to
      different molecules (the van der Waals interaction), and the hydrogen bond
      interaction, which occurs only for a particular orientation and displacement of a
      pair of molecules. The model is investigated by means of Monte Carlo simulations
      in the canonical and grand canonical ensembles. The Metropolis and the entropic
      sampling algorithms are used to obtain the thermodynamics of the system. We find
      that the entropic sampling prescription is the most efficient algorithm of them,
      providing information about the entropy and free energy of the system in a
      straightforward way. The curves for the polarization, number of hydrogen bonds,
      specific heat, and cumulant of energy were obtained as a function of the
      temperature and total concentration. In addition, the entropy of the
      noninteracting version of the model is compared to that of the angular trimers in
      a square lattice and triangles in a triangular lattice.

PMID- 15267401
TI  - The evaporation/condensation transition of liquid droplets.
AB  - The condensation of a supersaturated vapor enclosed in a finite system is
      considered. A phenomenological analysis reveals that the vapor is found to be
      stable at densities well above coexistence. The system size at which the
      supersaturated vapor condenses into a droplet is found to be governed by a
      typical length scale which depends on the coexistence densities, temperature and
      surface tension. When fluctuations are neglected, the chemical potential is seen
      to show a discontinuity at an effective spinodal point, where the inhomogeneous
      state becomes more stable than the homogeneous state. If fluctuations are taken
      into account, the transition is rounded, but the slope of the chemical potential
      versus density isotherm develops a discontinuity in the thermodynamic limit. In
      order to test the theoretical predictions, we perform a simulation study of
      droplet condensation for a Lennard-Jones fluid and obtain loops in the chemical
      potential versus density and pressure. By computing probability distributions for
      the cluster size, chemical potential, and internal energy, we confirm that the
      effective spinodal point may be identified with the occurrence of a first order
      phase transition, resulting in the condensation of a droplet. An accurate
      equation of state is employed in order to estimate the droplet size and the
      coexisting vapor density and good quantitative agreement with the simulation data
      is obtained. The results highlight the need of an accurate equation of state data
      for the Laplace equation to have predictive power.

PMID- 15267402
TI  - The relationship between crystal structure and methyl and t-butyl group dynamics
      in van der Waals organic solids.
AB  - We report x-ray diffractometry in a single crystal of 2-t-butyl-4-methylphenol
      (TMP) and low-frequency solid state nuclear magnetic resonance (NMR) proton
      relaxometry in a polycrystalline sample of TMP. The x-ray data show TMP to have a
      monoclinic, P2(1)/c, structure with eight molecules per unit cell and two
      crystallographically inequivalent t-butyl group (C(CH(3))(3)) sites. The proton
      spin-lattice relaxation rates were measured between 90 and 310 K at NMR
      frequencies of 8.50, 22.5, and 53.0 MHz. The relaxometry data is fitted with two
      models characterizing the dynamics of the t-butyl groups and their constituent
      methyl groups, both of which are consistent with the determined x-ray structure.
      In addition to presenting results for TMP, we review previously reported x-ray
      diffractometry and low-frequency NMR relaxometry in two other van der Waals
      solids which have a simpler structure. In both cases, a unique model for the
      reorientational dynamics was found. Finally, we review a similar previously
      reported analysis in a van der Waals solid with a very complex structure in which
      case fitting the NMR relaxometry requires very many parameters and serves mainly
      as a flag for a careful x-ray diffraction study.

PMID- 15267403
TI  - Translational and rotational diffusion of SF6 in zeolite NaY.
AB  - Temperature dependence of equilibrium as well as dynamical properties of SF(6) in
      zeolite NaY have been investigated by molecular dynamics simulation. By about 200
      K, SF(6) begins to have increased mobility. Strong orientational preference is
      exhibited by SF(6) during its passage through the 12-ring window, the bottleneck
      for diffusion. The preference is for orientation with C(3) followed by C(2) and
      then C(4) molecular symmetry axis perpendicular to the window plane.
      Translational motion is diffusive with an activation energy of 5.5 kJ/mol.
      Rotational-diffusion coefficient has an activation energy of 2.83 kJ/mol.
      Rotational motion is facile within the alpha-cage. Translational motion is
      hindered during passage through the 12-ring window when C(4) is perpendicular to
      the window plane. Orientational correlation functions P(1) and P(2) around C(2),
      C(3) and C(4) are reported. Only the long time decay of C(4) shows oscillations.
      This is attributed to the hindered rotation during intercage migration while
      passing through the 12-ring window.

PMID- 15267404
TI  - Orientational orders of small anisotropic molecules confined in slit pores.
AB  - Based on a constant-pressure Monte Carlo molecular simulation, we have studied
      orientationally ordered transitions of small anisotropic molecules confined in
      two parallel hard walls. These molecules are modeled by the hard Gaussian overlap
      model. The molecular elongations of the chosen molecules are so small that the
      molecules cannot form stable liquid-crystal (LC) phases in the bulk. But in the
      slit pores, we found, while the distance between two walls of the pores decreases
      to the molecular scale, an orientationally ordered phase can form. It shows that
      even hard confining surfaces favor the alignment of the small anisotropic
      molecules. Thus we conclude that the required molecular elongation for forming LC
      phases will decrease in confinement. Our results indicate that some non-LC small
      molecules may form stable LC phases due to the inducement of confining surfaces.

PMID- 15267405
TI  - High pressure reactivity of propene by first principles molecular dynamics
      calculations.
AB  - The reactivity of propene under high pressure has been investigated in the
      framework of Car-Parrinello molecular dynamics. Changes in structural and
      electronic properties due to pressure have been analyzed in systems with a
      density ranging from 0.855 to 2.151 g/cm(3). A ionic collective mechanism which
      leads to the formation of oligomers has been found by both spin restricted and
      spin polarized formalism. The maximally localized Wannier centers analysis has
      allowed us to characterize the addition scheme and to identify a Wannier center
      with a high spread value involved in the formation of the principal reaction
      products.

PMID- 15267406
TI  - Interfacial glass transition profiles in ultrathin, spin cast polymer films.
AB  - Interfacial glass transition temperature (T(g)) profiles in spin cast, ultrathin
      films of polystyrene and derivatives were investigated using shear-modulated
      scanning force microscopy. The transitions were measured as a function of film
      thickness (delta), molecular weight, and crosslinking density. The T(g)(delta)
      profiles were nonmonotonic and exhibited two regimes: (a) a sublayer extending
      about 10 nm from the substrate, with T(g) values lowered up to approximately 10
      degrees C below the bulk value, and (b) an intermediate regime extending over 200
      nm beyond the sublayer, with T(g) values exceeding the bulk value by up to 10
      degrees C. Increasing the molecular weight was found to shift the T(g)(delta)
      profiles further from the substrate interface, on the order of 10 nm/kDa.
      Crosslinking the precast films elevated the absolute T(g) values, but had no
      effect on the spatial length scale of the T(g)(delta) profiles. These results are
      explained in the context of film preparation history and its influence on
      molecular mobility. Specifically, the observed rheological anisotropy is
      interpreted based on the combined effects of shear-induced structuring and
      thermally activated interdiffusion.

PMID- 15267407
TI  - High-dimensional quantum dynamical study of the dissociation of H2 on Pd110.
AB  - We report the first six-dimensional quantum dynamical study of the dissociative
      adsorption of H(2) on a (110) surface. We have performed quantum coupled-channel
      calculations for the system H(2)/Pd(110) based on a potential energy surface
      (PES) that was derived from ab initio electronic structure calculations. In
      particular, we have focused on the effects of the corrugation and anisotropy of
      the PES on the H(2) dissociation probability. Our results agree well with the
      available experimental data for the sticking probability as a function of the
      initial kinetic energy and the angle of incidence. Because of the coupling
      between the anisotropy and corrugation of the potential energy surface our
      calculations predict an unusual rotational heating and a rather small rotational
      alignment in desorption.

PMID- 15267408
TI  - Local chemical reaction of benzene on Cu110 via STM-induced excitation.
AB  - We have investigated the mechanism of the chemical reaction of the benzene
      molecule adsorbed on Cu(110) surface induced by the injection of tunneling
      electrons using scanning tunneling microscopy (STM). With the dosing of tunneling
      electrons of the energy 2-5 eV from the STM tip to the molecule, we have detected
      the increase of the height of the benzene molecule by 40% in the STM image and
      the appearance of the vibration feature of the nu(C-H) mode in the inelastic
      tunneling spectroscopy (IETS) spectrum. It can be understood with a model in
      which the dissociation of C-H bonds occurs in a benzene molecule that induces a
      bonding geometry change from flat-lying to up-right configuration, which follows
      the story of the report of Lauhon and Ho on the STM-induced change of benzene on
      the Cu(100) surface. [L. J. Lauhon and W. Ho, J. Phys. Chem. A 104, 2463 (2000)].
      The reaction probability shows a sharp rise at the sample bias voltage at 2.4 V,
      which saturates at 3.0 V, which is followed by another sharp rise at the voltage
      of 4.3 V. No increase of the reaction yield is observed for the negative sample
      voltage up to 5 eV. In the case of a fully deuterated benzene molecule, it shows
      the onset at the same energy of 2.4 eV, but the reaction probability is 10(3)
      smaller than the case of the normal benzene molecule. We propose a model in which
      the dehydrogenation of the benzene molecule is induced by the formation of the
      temporal negative ion due to the trapping of the electrons at the unoccupied
      resonant states formed by the pi orbitals. The existence of the resonant level
      close to the Fermi level ( approximately 2.4 eV) and multiple levels in less than
      approximately 5 eV from the Fermi level, indicates a fairly strong interaction of
      the Cu-pi(*) state of the benzene molecule. We estimated that the large isotope
      effect of approximately 10(3) can be accounted for with the Menzel-Gomer-Redhead
      (MGR) model with an assumption of a shallow potential curve for the excited
      state.

PMID- 15267409
TI  - Poisson-Boltzmann theory of the charge-induced adsorption of semi-flexible
      polyelectrolytes.
AB  - A model is suggested for the structure of an adsorbed layer of a highly charged
      semi-flexible polyelectrolyte on a weakly charged surface of opposite charge
      sign. The adsorbed phase is thin, owing to the effective reversal of the charge
      sign of the surface upon adsorption, and ordered, owing to the high surface
      density of polyelectrolyte strands caused by the generally strong binding between
      polyelectrolyte and surface. The Poisson-Boltzmann equation for the electrostatic
      interaction between the array of adsorbed polyelectrolytes and the charged
      surface is solved for a cylindrical geometry, both numerically, using a finite
      element method, and analytically within the weak curvature limit under the
      assumption of excess monovalent salt. For small separations, repulsive surface
      polarization and counterion osmotic pressure effects dominate over the
      electrostatic attraction and the resulting electrostatic interaction curve shows
      a minimum at nonzero separations on the Angstrom scale. The equilibrium density
      of the adsorbed phase is obtained by minimizing the total free energy under the
      condition of equality of chemical potential and osmotic pressure of the
      polyelectrolyte in solution and in the adsorbed phase. For a wide range of ionic
      conditions and charge densities of the charged surface, the interstrand
      separation as predicted by the Poisson-Boltzmann model and the analytical theory
      closely agree. For low to moderate charge densities of the adsorbing surface, the
      interstrand spacing decreases as a function of the charge density of the charged
      surface. Above about 0.1 M excess monovalent salt, it is only weakly dependent on
      the ionic strength. At high charge densities of the adsorbing surface, the
      interstrand spacing increases with increasing ionic strength, in line with the
      experiments by Fang and Yang [J. Phys. Chem. B 101, 441 (1997)].

PMID- 15267410
TI  - Influences of hydration force and elastic strain energy on the stability of solid
      film in a very thin solid-on-liquid structure.
AB  - Since hydration forces become very strong at short range and are particularly
      important for determining the magnitude of the adhesion between two surfaces or
      interaction energy, the influences of the hydration force and elastic strain
      energy due to hydration-induced layering of liquid molecules close to a solid
      film surface on the stability of a solid film in a solid-on-liquid (SOL)
      nanostructure are studied in this paper. The liquid of this thin SOL structure is
      a kind of water solution. Since the surface forces play an important role in the
      structure, the total free energy change of SOL structures consists of the changes
      in the bulk elastic energy within the solid film, the surface energy at the solid
      liquid interface and the solid-air interface, and highly nonlinear volumetric
      component associated with interfacial forces. The critical wavelength of one
      dimensional undulation, the critical thickness of the solid film, and the
      critical thickness of the liquid layer are studied, and the stability regions of
      the solid film have been determined. Emphasis is placed on calculation of
      critical values, which are the basis of analyzing the stability of the very thin
      solid film.

PMID- 15267411
TI  - Vibrational behavior of adsorbed CO2 on single-walled carbon nanotubes.
AB  - We present theoretical and experimental evidence for CO(2) adsorption on
      different sites of single walled carbon nanotube (SWNT) bundles. We use local
      density approximation density functional theory (LDA-DFT) calculations to compute
      the adsorption energies and vibrational frequencies for CO(2) adsorbed on SWNT
      bundles. The LDA-DFT calculations give a range of shifts for the asymmetric
      stretching mode from about -6 to -20 cm(-1) for internally bound CO(2), and a
      range from -4 to -16 cm(-1) for externally bound CO(2) at low densities. The
      magnitude of the shift is larger for CO(2) adsorbed parallel to the SWNT surface;
      various perpendicular configurations yield much smaller theoretical shifts. The
      asymmetric stretching mode for CO(2) adsorbed in groove sites and interstitial
      sites exhibits calculated shifts of -22.2 and -23.8 cm(-1), respectively. The
      calculations show that vibrational mode softening is due to three effects: (1)
      dynamic image charges in the nanotube; (2) the confining effect of the adsorption
      potential; (3) dynamic dipole coupling with other adsorbate molecules. Infrared
      measurements indicate that two families of CO(2) adsorption sites are present.
      One family, exhibiting a shift of about -20 cm(-1) is assigned to internally
      bound CO(2) molecules in a parallel configuration. This type of CO(2) is readily
      displaced by Xe, a test for densely populated adsorbed species, which are
      expected to be present on the highest adsorption energy sites in the interior of
      the nanotubes. The second family exhibits a shift of about -7 cm(-1) and the site
      location and configuration for these species is ambiguous, based on comparison
      with the theoretical shifts. The population of the internally bound CO(2) may be
      enhanced by established etching procedures that open the entry ports for
      adsorption, namely, ozone oxidation followed by annealing in vacuum at 873 K.
      Xenon displacement experiments indicate that internally bound CO(2) is
      preferentially displaced relative to the -7 cm(-1) shifted species. The -7 cm(-1)
      shifted species is assigned to CO(2) adsorbed on the external surface based on
      results from etching and Xe displacement experiments.

PMID- 15267412
TI  - Free energy, energy, and entropy of swelling in Cs-, Na-, and Sr-montmorillonite
      clays.
AB  - A Monte Carlo method for grand canonical and grand isoshear ensemble simulations
      has been used to characterize the free energy, energy, and entropy of clay
      mineral swelling. The Monte Carlo approach was found to be more efficient at
      simulating water content fluctuations in the highly constrained clay environment
      than a previously developed molecular dynamics method. Swelling thermodynamics
      calculated for Cs-, Na-, and Sr-montmorillonite clays indicate a strong
      dependence of swelling on the interlayer ion identity, in agreement with various
      experimental measurements. The Sr clay swells most readily, and both the Na and
      Sr clays prefer expanded states (two-layer hydrate or greater) when in contact
      with bulk water. In contrast, swelling is inhibited in the Cs clay. Differences
      in swelling behavior are traced directly to the tendency of the different ions to
      hydrate. The swelling free energies are decomposed into their energetic and
      entropic components, revealing an overall energetic driving force for the
      swelling phenomena. Entropic effects provide a smaller, mediating role in the
      swelling processes. The results provide a unique molecular perspective on
      experimentally well-characterized swelling phenomena.

PMID- 15267413
TI  - Modeling molecular transport in slit pores.
AB  - We examine the transport of methane in microporous carbon by performing
      equilibrium and nonequilibrium molecular dynamics simulations over a range of
      pore sizes, densities, and temperatures. We interpret these simulation results
      using two models of the transport process. At low densities, we consider a
      molecular flow model, in which intermolecular interactions are neglected, and
      find excellent agreement between transport diffusion coefficients determined from
      simulation, and those predicted by the model. Simulation results indicate that
      the model can be applied up to fluid densities of the order to 0.1-1 nm(-3).
      Above these densities, we consider a slip flow model, combining hydrodynamic
      theory with a slip condition at the solid-fluid interface. As the diffusion
      coefficient at low densities can be accurately determined by the molecular flow
      model, we also consider a model where the slip condition is supplied by the
      molecular flow model. We find that both density-dependent models provide a useful
      means of estimating the transport coefficient that compares well with simulation.

PMID- 15267414
TI  - The interface between benzenes (C6H6;C6H5Cl;2-C6H4OHCl) and amorphous solid water
      studied with metastable impact electron spectroscopy and ultraviolet
      photoelectron spectroscopy (HeI and II).
AB  - Interfaces between films of benzenes (C(6)H(6);C(6)H(5)Cl;2-C(6)H(4)OHCl) and
      solid H(2)O on tungsten substrates were studied between 80 and 200 K with
      metastable impact electron spectroscopy (MIES) and ultraviolet photoelectron
      spectroscopy [UPS(HeI and II)]. The following cases were studied in detail: (i)
      Adsorption of the benzenes on solid water in order to simulate their interaction
      with ice particles, and (ii) deposition of water on benzene films in order to
      simulate the process of water precipitation. In all cases the prepared
      interfacial layers were annealed up to 200 K under in situ control of MIES and
      UPS. The different behavior of the interfaces for the three studied cases is
      traced back to the different mobilities of the molecules with respect to that of
      water. The interaction between H(2)O and the benzenes at the interfaces is
      discussed on the basis of a qualitative profile for the free energy of that
      component of the interface which has the larger mobility. Possible implications
      of the present results for atmospheric physics are briefly mentioned.

PMID- 15267415
TI  - Effects of carbon on the stability and chemical performance of transition metal
      carbides: a density functional study.
AB  - Density functional theory was employed to study the stabilities and chemical
      activities of transition metal carbides. Here we take the well-known Mo carbides
      and Ti carbides as an example. Different kinds of structures including the bulk
      surfaces [Mo(2)C(001), MoC(001), and TiC(001)] and metcars [Mo(8)C(12) and
      Ti(8)C(12)] are taken into consideration. Systematic studies show that by raising
      the C coordination number of the metal atoms in the carbides, in general the
      stability of the carbides increases (metcars are an exception since they include
      both high-coordinated and low-coordinated metal atoms.); at the same time, the
      chemical activities of the carbides decrease due to a downshift of the metal d
      band center (ligand effect). Considering the better catalysts those that combine
      high stability and moderate chemical activity, our results suggest that the
      catalytic potential of Mo carbide systems should decrease in the following
      sequence: Mo(8)C(12)>Mo(2)C(001) or MoC(001)>pure Mo(110). In spite of having the
      largest C/Mo ratio, the metcar appears as the most attractive system. Our studies
      also indicate that the "magic" behavior of metcars is not unique for Mo carbides.
      Similar behavior is also observed for Ti carbides. This implies that
      nanoparticles like metcar species could exhibit better performances than the
      corresponding bulk metal carbides as catalysts.

PMID- 15267416
TI  - Hydrogen desorption kinetics from the Si(1-x)Gex(100)-(2x1) surface.
AB  - We study the influence of germanium atoms upon molecular hydrogen desorption
      energetics using density functional cluster calculations. A three-dimer cluster
      is used to model the Si((1-x))Ge(x)(100)-(2x1) surface. The relative stabilities
      of the various monohydride and clean surface configurations are computed. We also
      compute the energy barriers for desorption from silicon, germanium, and mixed
      dimers with various neighboring configurations of silicon and germanium atoms.
      Our results indicate that there are two desorption channels from mixed dimers,
      one with an energy barrier close to that for desorption from germanium dimers and
      one with an energy barrier close to that for desorption from silicon dimers.
      Coupled with the preferential formation of mixed dimers over silicon or germanium
      dimers on the surface, our results suggest that the low barrier mixed dimer
      channel plays an important role in hydrogen desorption from silicon-germanium
      surfaces. A simple kinetics model is used to show that reasonable thermal
      desorption spectra result from incorporating this channel into the mechanism for
      hydrogen desorption. Our results help to resolve the discrepancy between the
      surface germanium coverage found from thermal desorption spectra analysis, and
      the results of composition measurements using photoemission experiments. We also
      find from our cluster calculations that germanium dimers exert little influence
      upon the hydrogen desorption barriers of neighboring silicon or germanium dimers.
      However, a relatively larger effect upon the desorption barrier is observed in
      our calculations when germanium atoms are present in the second layer.

PMID- 15267417
TI  - Isometric graphing and multidimensional scaling for reaction-diffusion modeling
      on regular and fractal surfaces with spatiotemporal pattern recognition.
AB  - Heterogeneous surface reactions exhibiting complex spatiotemporal dynamics and
      patterns can be studied as processes involving reaction-diffusion mechanisms. In
      many realistic situations, the surface has fractal characteristics. This
      situation is studied by isometric graphing and multidimensional scaling (IGMDS)
      of fractal surfaces for extracting geodesic distances (i.e., shortest scaled
      distances that obtain edges of neighboring surface nodes and their
      interconnections) and the results obtained used to model effects of surface
      diffusion with nonlinear reactions. Further analysis of evolved spatiotemporal
      patterns may be carried out by IGMDS because high-dimensional snapshot data can
      be efficiently projected to a transformed subspace with reduced dimensions.
      Validation of the IGMDS methodology is carried out by comparing results with
      reduction capabilities of conventional principal component analysis for simple
      situations of reaction and diffusion on surfaces. The usefulness of the IGMDS
      methodology is shown for analysis of complex patterns formed on both regular and
      fractal surfaces, and using generic nonlinear reaction-diffusion systems
      following FitzHugh Nagumo and cubic reaction kinetics. The studies of these
      systems with nonlinear kinetics and noise show that effects of surface disorder
      due to fractality can become very relevant. The relevance is shown by studying
      properties of dynamical invariants in IGMDS component space, viz., the Lyapunov
      exponents and the KS entropy for interesting situations of spiral formation and
      turbulent patterns.

PMID- 15267418
TI  - Plasmon hybridization in spherical nanoparticles.
AB  - We show that the plasmon resonances in single metallic nanoshells and multiple
      concentric metallic shell particles can be understood in terms of interaction
      between the bare plasmon modes of the individual surfaces of the metallic shells.
      The interaction of these elementary plasmons results in hybridized plasmons whose
      energy can be tuned over a wide range of optical and infrared wavelengths. The
      approach can easily be generalized to more complex systems, such as dimers and
      small nanoparticle aggregates.

PMID- 15267419
TI  - Johari-Goldstein relaxation and crystallization of sorbitol to ordered and
      disordered phases.
AB  - The equilibrium permittivity epsilon(s) and the dielectric relaxation spectra of
      supercooled liquid D-sorbitol were measured during its crystallization to
      orientationally disordered or ordered phases depending on the sample preparation
      procedure at several fixed temperatures up to a period of 6 days. The epsilon(s)
      measurements showed that when the sample was contaminated by a minute amount of
      crystals, it crystallized to an ordered phase. When the liquid was not
      contaminated, the sample crystallized to an orientationally disordered phase.
      When supercooled D-sorbitol was kept close to its T(g), its dielectric spectra
      did not change over a period of 138.5 h. It was found that the Johari-Goldstein
      (JG) relaxation rate of the orientationally disordered crystalline phase is
      higher in comparison with that of the supercooled liquid, the spectrum broader,
      and the relaxation strength lower. Its glasslike transition temperature is higher
      than T(g) of the liquid. The results on crystallization showed that the
      structural changes occurring at a temperature where the alpha relaxation emerges
      from the JG relaxation affects the crystallization kinetics of the liquid.

PMID- 15267420
TI  - Hydrogen atom formation from the photodissociation of water ice at 193 nm.
AB  - The TOF spectra of photofragment hydrogen atoms from the 193 nm photodissociation
      of amorphous ice at 90-140 K have been measured. The spectra consist of both a
      fast and a slow components that are characterized by average translational
      energies of 2k(B)T(trans)=0.39+/-0.04 eV (2300+/-200 K) and 0.02 eV (120+/-20 K),
      respectively. The incident laser power dependency of the hydrogen atom production
      suggests one-photon process. The electronic excitation energy of a branched
      cluster, (H(2)O)(6+1), has been theoretically calculated, where (H(2)O)(6+1) is a
      (H(2)O)(6) cyclic cluster attached by a water molecule with the hydrogen bond.
      The photoabsorption of this branched cluster is expected to appear at around 200
      nm. The source of the hydrogen atoms is attributed to the photodissociation of
      the ice surface that is attached by water molecules with the hydrogen bond.
      Atmospheric implications are estimated for the photodissociation of the ice
      particles (Noctilucent clouds) at 190-230 nm in the region between 80 and 85 km
      altitude.

PMID- 15267421
TI  - Elastic behavior of short compact polymers.
AB  - In this paper, we investigate the elastic behaviors of short compact polymers
      using the enumeration calculation method and the HP model on a two-dimensional
      square lattice. Both the mean-square end-to-end distance R(2) and the ratio of
      R(2)/S(2) increase with lambda. However, when the elongation ratio becomes
      larger, the curves of R(2)/S(2) become smooth and they are close to the limit of
      10.50 for different compact polymers. We also investigate the changes of interior
      conformations in the process of tensile elongation through calculating the
      probabilities of three bond angles (i.e., 90 degrees, 180 degrees, and 270
      degrees). The average energy and Helmholtz free energy per bond are both negative
      and increase with elongation ratio lambda. In the meantime, the elastic force per
      bond (f ) also increases with elongation ratio lambda, and the energy
      contribution to the elastic force (f(U)) increases first and then drops, and
      there exists the maximum of f(U) in the region of lambda=1.40-1.80 for different
      sequences. The entropy contribution to force (f(S)) is close to zero at a small
      elongation ratio lambda and then increases with lambda. Some comparisons with
      different sequences (including nonfolding and folding sequences) are also made.

PMID- 15267422
TI  - Spreading of block copolymer films and domain alignment at moving terrace steps.
AB  - We investigate spreading of phase separated copolymer films, where domain walls
      and thickness steps influence polymer flow. We show that at early stages of
      spreading its rate is determined by slow activated flow at terrace steps (i.e.,
      thickness steps). At late stages of spreading, on the other hand, the rate is
      determined by the flow along terraces, with diffusionlike time dependence t(
      1/2). This dependence is similar to de Gennes and Cazabat's prediction for
      generic layered liquids [P. G. de Gennes and A. M. Cazabat, C.R. Acad. Sci. Paris
      II 310, 1601 (1990)], as opposed to the classical Tanner's law of drop spreading.
      We also argue that chain hopping at the spreading terrace steps should lead to
      the formation of aligned, defect-free domain patterns on the growing terraces.

PMID- 15267423
TI  - Cubatic phase for tetrapods.
AB  - We investigate the phase behavior of tetrapods, hard nonconvex bodies formed by
      four rods connected under tetrahedral angles. We predict that, depending on the
      relative lengths of the rods these particles can form a uniaxial nematic phase,
      and more surprisingly they can exhibit a cubatic phase, a special case of the
      biaxial nematic phase. These predictions may be experimentally testable, as
      experimental realizations of tetrapods have recently become available.

PMID- 15267424
TI  - Observation of electrostatically released DNA from gold electrodes with
      controlled threshold voltages.
AB  - DNA oligo-nucleotides, localized at Au metal electrodes in aqueous solution, are
      found to be released when applying a negative bias voltage to the electrode. The
      release was confirmed by monitoring the intensity of the fluorescence of cyanine
      dyes (Cy3) linked to the 5' end of the DNA. The threshold voltage of the release
      changes depending on the kind of linker added to the DNA 3'-terminal. The amount
      of released DNA depends on the duration of the voltage pulse. Using this
      technique, we can retain DNA at Au electrodes or Au needles, and release the
      desired amount of DNA at a precise location in a target. The results suggest that
      DNA injection into living cells is possible with this method.

PMID- 15267425
TI  - Rotational spectrum of cis-cis HOONO.
AB  - The pure rotational spectrum of cis-cis peroxynitrous acid, HOONO, has been
      observed. Over 220 transitions, sampling states up to J'=67 and Ka'=31, have been
      fitted with an rms uncertainty of 48.4 kHz. The experimentally determined
      rotational constants agree well with ab initio values for the cis-cis conformer,
      a five-membered ring formed by intramolecular hydrogen bonding. The small,
      positive inertial defect Delta=0.075667(60) amu A2 and lack of any observable
      torsional splittings in the spectrum indicate that cis-cis HOONO exists in a well
      defined planar structure at room temperature.

PMID- 15267426
TI  - Generalized monotonically convergent algorithms for solving quantum optimal
      control problems.
AB  - A wide range of cost functionals that describe the criteria for designing optimal
      pulses can be reduced to two basic functionals by the introduction of product
      spaces. We extend previous monotonically convergent algorithms to solve the
      generalized pulse design equations derived from those basic functionals. The new
      algorithms are proved to exhibit monotonic convergence. Numerical tests are
      implemented in four-level model systems employing stationary and/or nonstationary
      targets in the absence and/or presence of relaxation. Trajectory plots that
      conveniently present the global nature of the convergence behavior show that slow
      convergence may often be attributed to "trapping" and that relaxation processes
      may remove such unfavorable behavior.

PMID- 15267427
TI  - Three-dimensional Ewald method with correction term for a system periodic in one
      direction.
AB  - A three-dimensional Ewald summation formula with a shape-dependent correction
      term for Coulomb interactions in systems with one-dimensional periodicity is
      derived. Test molecular dynamics simulations of acetone molecules in cylindrical
      silica pores show that the formula is efficient only when size of the system in a
      plane perpendicular to the periodicity direction is small in comparison with the
      periodicity length.

PMID- 15267428
TI  - Relativistic double group spinor representations of nonrigid molecules.
AB  - The character theory of relativistic double group spinor representations is
      developed in order to represent the total rovibronic states of nonrigid
      molecules. It is shown that the double groups can be represented in terms of
      wreath products and powerful matrix cycle type generators that are used to
      construct their character tables. It is shown that these tables are of use when
      spin-orbit coupling is included in the Hamiltonian even for molecules containing
      lighter atoms. Applications to nonrigid molecules such as Tl2H4/Tl2H4+ are
      considered. It is shown that the tunneling splittings and the nuclear spin
      statistical weights can be obtained for such species using the character tables
      thus constructed. The spinor double groups of several other molecules such as
      hexamethyl dilead and heavy weakly bound clusters such as (PoH2)4 are also
      considered.

PMID- 15267429
TI  - Multicanonical basin hopping: a new global optimization method for complex
      systems.
AB  - We introduce a new optimization algorithm that combines the basin-hopping method,
      which can be used to efficiently map out an energy landscape associated with
      minima, with the multicanonical Monte Carlo method, which encourages the system
      to move out of energy traps during the computation. As an example of implementing
      the algorithm for the global minimization of a multivariable system, we consider
      the Lennard-Jones systems containing 150-185 particles, and find that the new
      algorithm is more efficient than the original basin-hopping method.

PMID- 15267430
TI  - Non-Born-Oppenheimer trajectories with self-consistent decay of mixing.
AB  - A semiclassical trajectory method, called the self-consistent decay of mixing
      (SCDM) method, is presented for the treatment of electronically nonadiabatic
      dynamics. The SCDM method is a modification of the semiclassical Ehrenfest (SE)
      method (also called the semiclassical time-dependent self-consistent-field
      method) that solves the problem of unphysical mixed final states by including
      decay-of-mixing terms in the equations for the evolution of the electronic state
      populations. These terms generate a force, called the decoherent force (or
      dephasing force), that drives the electronic component of each trajectory toward
      a pure state. Results for several mixed quantum-classical methods, in particular
      the SCDM, SE, and natural-decay-of-mixing methods and several trajectory surface
      hopping methods, are compared to the results of accurate quantum mechanical
      calculations for 12 cases involving five different fully dimensional triatomic
      model systems. The SCDM method is found to be the most accurate of the methods
      tested. The method should be useful for the simulation of photochemical
      reactions.

PMID- 15267431
TI  - An alternative multipolar expansion for intermolecular potential functions.
AB  - We have derived a new multipolar expansion for intermolecular potential-energy
      functions with applications in molecular physics, theoretical chemistry, and
      mathematical physics. The new formulation employs a separation of radial and
      angular terms with a simple index structure that leads to computational
      efficiency and ease of physical interpretation. For the case of the Coulomb
      interaction, we compare the present formulation with two conventional multipole
      expansions: the Cartesian tensor and the irreducible spherical tensor expansions.
      The new formalism leads to efficient numerical algorithms that are useful for
      general applications beyond intermolecular potentials. In addition to the
      electrostatic Coulomb interaction, we illustrate the formalism with applications
      to special function theory and a bipolar expansion involved in potential theory.

PMID- 15267432
TI  - Solution of the linearized Poisson-Boltzmann equation.
AB  - Improved methods are formulated for solution of the linearized Poisson-Boltzmann
      equation, to be used in conjunction with electronic structure calculation on a
      solute together with dielectric continuum representation of the salt-containing
      solvent. Volume polarization effects due to quantum mechanical penetration of
      solute charge density outside the cavity that excludes solvent are treated by
      exact and by approximate methods analogous to those previously developed for the
      salt-free case. With boundary element approaches, exact solutions lead to coupled
      equations for a pair of cavity surface distributions that mimic the polarization
      of the solvent dielectric and the ionic atmosphere. A novel means is found to
      effectively decouple these equations, yielding more efficient practical methods
      for their numerical solution. Detailed comparisons are given to related boundary
      element formulations previously reported in the literature, which neglect volume
      polarization, and analogous decoupling is also found for the pair of surface
      distributions invoked there. Illustrative results are provided for a simple
      spherical example.

PMID- 15267433
TI  - Molecular dynamic simulation methods for anisotropic liquids.
AB  - Methods of molecular dynamics simulations for anisotropic molecules are
      presented. The new methods, with an anisotropic factor in the cell dynamics,
      dramatically reduce the artifacts related to cell shapes and overcome the
      difficulties of simulating anisotropic molecules under constant hydrostatic
      pressure or constant volume. The methods are especially effective for anisotropic
      liquids, such as smectic liquid crystals and membranes, of which the stacks of
      layers are compressible (elastic in direction perpendicular to the layers) while
      the layer itself is liquid and only elastic under uniform compressive force. The
      methods can also be used for crystals and isotropic liquids as well.

PMID- 15267434
TI  - Inelastic collisions of molecular hydrogen: a comparison of results from quantum
      and classical mechanics.
AB  - Full-dimensional quantum and classical calculations have been carried out for
      inelastic (nonreactive) energy transfer in H2+H2 on the ab initio potential
      energy surface of Boothroyd et al. [J. Chem. Phys. 116, 666 (2002)]. State-to
      state cross sections are determined and compared for transitions from
      H2(0,j(ab))+H2(1,j(cd)). While there is excellent agreement for transitions
      involving small Deltaj, for larger Deltaj and for vibrational relaxation,
      significant differences are observed which exhibit no systematic trends. Reasons
      for this disagreement are discussed.

PMID- 15267435
TI  - Relaxation of H2O from its /04>- vibrational state in collisions with H2O, Ar,
      H2, N2, and O2.
AB  - We report rate coefficients at 293 K for the collisional relaxation of H2O
      molecules from the highly excited /04>(+/-) vibrational states in collisions with
      H2O, Ar, H2, N2, and O2. In our experiments, the mid R:04(-) state is populated
      by direct absorption of radiation from a pulsed dye laser tuned to approximately
      719 nm. Evolution of the population in the (/04>(+/-)) levels is observed using
      the combination of a frequency-quadrupled Nd:YAG laser, which selectively
      photolyses H2O(/04>(+/-)), and a frequency-doubled dye laser, which observes the
      OH(v=0) produced by photodissociation via laser-induced fluorescence. The delay
      between the pulse from the pump laser and those from the photolysis and probe
      lasers was systematically varied to generate kinetic decays. The rate
      coefficients for relaxation of H2O(/04>(+/-)) obtained from these experiments, in
      units of cm3 molecule(-1) s(-1), are: k(H2O)=(4.1+/-1.2) x 10(-10), k(Ar)=(4.9+/
      1.1) x 10(-12), k(H2)=(6.8+/-1.1) x 10(-12), k(N2)=(7.7+/-1.5) x 10(-12),
      k(O2)=(6.7+/-1.4) x 10(-12). The implications of these results for our previous
      reports of rate constants for the removal of H2O molecules in selected
      vibrational states by collisions with H atoms (P. W. Barnes et al., Faraday
      Discuss. Chem. Soc. 113, 167 (1999) and P. W. Barnes et al., J. Chem. Phys. 115,
      4586 (2001).) are fully discussed.

PMID- 15267436
TI  - A study on the anisole-water complex by molecular beam-electronic spectroscopy
      and molecular mechanics calculations.
AB  - An experimental and theoretical study is made on the anisole-water complex. It is
      the first van der Waals complex studied by high resolution electronic
      spectroscopy in which the water is seen acting as an acid. Vibronically and
      rotationally resolved electronic spectroscopy experiments and molecular mechanics
      calculations are used to elucidate the structure of the complex in the ground and
      first electronic excited state. Some internal dynamics in the system is revealed
      by high resolution spectroscopy.

PMID- 15267437
TI  - Quantum initial value representation simulation of water trimer far infrared
      absorption spectrum.
AB  - We extend the technique of quantum propagation on a grid of trajectory guided
      coupled coherent states to simulate experimental absorption spectra. The approach
      involves calculating the thermally averaged dipole moment autocorrelation
      function by means of quantum propagation in imaginary time. The method is tested
      on simulation of the far infrared spectrum of water trimer based on a three
      dimensional model potential. Results are in good agreement with experiment and
      with other calculations.

PMID- 15267438
TI  - Dissociative ionization of methane by chirped pulses of intense laser light.
AB  - Measurements have been made of optical field-induced ionization and fragmentation
      of methane molecules at laser intensities in the 10(16) W cm(-2) range using near
      transform limited pulses of 100 fs duration as well as with chirped pulses whose
      temporal profiles extend up to 1500 fs. Data is taken both in constant-intensity
      and constant-energy modes. The temporal profile of the chirped laser pulse is
      found to affect the morphology of the fragmentation pattern that is measured.
      Besides, the sign of the chirp also affects the yield of fragments like C2+, H+,
      and H2+ that originate from methane dications that are formed by optical field
      induced double ionization.

PMID- 15267439
TI  - Comparison of spectroscopic potentials and an a priori analytical function. The
      potential energy curve of the ground state of the sodium dimer, X1Sigmag(+) Na2.
AB  - The results of a "universal" potential energy function, one that incorporates
      electronegativity and Slater's effective nuclear charge into a Morse-type
      function, are compared to spectroscopically derived potential energy curves of
      the X1Sigmag(+) state of Na2. The function is a priori in that it does not
      require prior knowledge of the actual potential and has no adjustable parameters.
      Criteria used to evaluate the performance of the function are comparisons of
      predicted versus spectroscopic energies at Rydberg-Klein-Rees (RKR) procedure
      turning points, predicted distances at measured energies versus RKR distances,
      and eigenvalues derived from the a priori potential versus spectroscopically
      deduced energy levels. The a priori function describes the Na2 potential with
      deviations approaching the magnitude of those found among some spectroscopic
      potentials from different sources. By examining the behavior of the
      "spectroscopic" parameter of the Morse function, irregularities are found in five
      of the seven spectroscopic potentials examined. A new procedure is demonstrated
      for correcting irregularities on the inner branch of spectroscopic potentials at
      high extents of dissociation and for extending reliably the potential in this
      region beyond the domain of the measurements.

PMID- 15267440
TI  - Vibrational dynamics of 9-fluorenemethanol using infrared-ultraviolet double
      resonance spectroscopy.
AB  - Vibrational spectroscopy of jet-cooled 9-fluorenemethanol and its clusters 9
      fluorenemethanol-H2O, 9-fluorenemethanol-CH3OH, 9-fluorenemethanol-C2H5OH, and 9
      fluorenemethanol-C3H7OH has been carried out using an IR-UV double-resonance
      method. The spectrum of the OH stretching vibration, v(OH), has been measured for
      the 9-fluorenemethanol monomer and for each of the clusters. Two conformers of 9
      fluorenemethanol, symmetric (sym) and unsymmetric (unsym), have been identified
      using a combination of spectroscopy and quantum chemical calculations with B3LYP
      and HF methods using the 6-31G(d) basis set. Vibrational dynamics resulting from
      IR excitation has also been studied using the S0-S1 transition probed by a
      nanosecond-time-delayed UV laser. The data suggest that isomerization occurs as a
      result of the IR excitation, but the breadth of the probe spectra makes an
      unequivocal conclusion difficult. The effect of hydrogen bonding on the v(OH) of
      9-fluorenemethanol has also been studied in clusters with water, methanol,
      ethanol, and propanol by measuring the IR spectra. Cluster dissociation dynamics
      have also been studied following IR excitation. It is observed that upon
      excitation of the cluster of a particular conformation the monomer product is
      generally produced in both conformer forms. Energetic considerations indicate
      that isomerization occurs before dissociation.

PMID- 15267441
TI  - Quantal density functional theory of the hydrogen molecule.
AB  - In this paper we perform a quantal density functional theory (Q-DFT) study of the
      hydrogen molecule in its ground state. In common with traditional Kohn-Sham
      density functional theory, Q-DFT transforms the interacting system as described
      by Schrodinger theory, to one of noninteracting fermions--the S system--such that
      the equivalent density, total energy, and ionization potential are obtained. The
      Q-DFT description of the S system is in terms of "classical" fields and their
      quantal sources that are quantum-mechanical expectations of Hermitian operators
      taken with respect to the interacting and S system wave functions. The sources,
      and hence the fields, are separately representative of all the many-body effects
      the S system must account for, viz. electron correlations due to the Pauli
      exclusion principle, Coulomb repulsion, and correlation-kinetic effects. The
      local electron-interaction potential energy of each model fermion is the work
      done to move it in the force of a conservative effective field that is the sum of
      the individual fields. The Hartree, Pauli, Coulomb, and correlation-kinetic
      energy components of the total energy are also expressed in virial form in terms
      of the corresponding fields. The highest occupied eigenvalue of the S system is
      the negative of the ionization potential energy. The Q-DFT analysis of the
      hydrogen molecule is performed employing the highly accurate correlated wave
      function of Kolos and Roothaan.

PMID- 15267442
TI  - First stretching overtone of BiH3: an extreme local-mode case for XH3-type
      molecule?
AB  - The first stretching overtone region of short-lived, formerly inaccessible BiH3
      near 3405 cm(-1) has been measured by Fourier-transform infrared spectroscopy
      with a resolution of 0.0066 cm(-1). Only the 2nu1(A1)/nu1+nu3(E) band system has
      been observed. Rotational analysis, with transitions reaching J'max=14, has
      revealed almost perfect local-mode behavior for the upper states denoted as
      (200A1/E) in the local-mode notation. Ratios of vibration-rotation interaction
      parameters q(eff)/alpha(eff)(BB) and r(eff)/alpha(eff)(BC), and the appropriate
      rotational constant differences, are in good agreement with theoretical local
      mode limit values. A simple stretching vibrational model reproduces the observed
      vibrational term values well, and the potential parameters obtained are close to
      true values.

PMID- 15267443
TI  - Density of phonon states in solid parahydrogen from inelastic neutron scattering.
AB  - We have measured the inelastic neutron scattering spectrum of solid parahydrogen
      (at low pressure and T=13.3 K) using the thermal original spectrometer with
      cylindrical analyzers spectrometer at the ISIS pulsed neutron source (UK). From
      the experimental spectrum we have obtained the parahydrogen density of phonon
      states which has been compared with the estimates available in the literature.
      The present determination improves substantially the previous experimental
      scenario from the point of view of both statistics and accuracy. The comparison
      with the most recent estimate obtained from a quantum mechanical simulation of
      the molecular dynamics calls for an improvement of the computational methods..

PMID- 15267444
TI  - Mixing rules for multicomponent mixture mass diffusion coefficients and thermal
      diffusion factors.
AB  - Mixing rules are derived for mass diffusion coefficient and thermal diffusion
      factor matrices by developing compatibility conditions between the fluid mixture
      equations obtained from nonequilibrium thermodynamics and Grad's 13-moment
      kinetic theory. The mixing rules are shown to be in terms of the species mole
      fractions and binary processes. In particular, the thermal diffusion factors for
      binary mixtures obtained by the Chapman-Enskog expansion procedure are suitably
      generalized for many-component mixtures. Some practical aspects of the results
      are discussed including the utilization of these mixing rules for high pressure
      situations.

PMID- 15267445
TI  - The elementary steps of the photodissociation and recombination reactions of
      iodine molecules enclosed in cages and channels of zeolite crystals: a
      femtosecond time-resolved study of the geometry effect.
AB  - We present femtosecond time-resolved pump-probe experiments on iodine molecules
      enclosed into well-defined cages and channels of different crystalline SiO2
      modifications of zeolites. The new experimental results obtained from iodine in
      TON (Silica-ZSM-22), FER (Silica-Ferrierit), and MFI (Silicalit-1) porosils are
      compared with data published earlier on the iodine/DDR (Decadodecasil 3R) porosil
      system [Flachenecker et al., Phys. Chem. Chem. Phys. 5, 865 (2003)]. A summary of
      all findings is given. The processes analyzed by means of the ultrafast
      spectroscopy are the vibrational relaxation as well as the dissociation and
      recombination reactions, which are caused by the interaction of the photo-excited
      iodine molecules with the cavity walls of the porosils. A clear dependence of the
      observed dynamics on the geometry of the surrounding lattice structure can be
      seen. These measurements are supported by temperature-dependent experiments.
      Making use of a theoretical model which is based on the classical Langevin
      equation, an analysis of the geometry-reaction relation is performed. The
      Brownian dynamics simulations show that in contrast to the vibrational relaxation
      the predissociation dynamics are independent of the frequency of collisions with
      the surroundings. From the results obtained in the different surroundings, we
      conclude that mainly local fields are responsible for the crossing from the bound
      B state to the repulsive a/a' states of the iodine molecules.

PMID- 15267446
TI  - Insulator to metal transition in fluid deuterium.
AB  - We have investigated the insulator to metal transition in fluid deuterium using
      first principles simulations. Both density functional and quantum Monte Carlo
      calculations indicate that the electronic energy gap of the liquid vanishes at
      about ninefold compression and 3000 K. At these conditions the computed
      conductivity values are characteristic of a poor metal. These findings are
      consistent with those of recent shock wave experiments but the computed
      conductivity is larger than the measured value. From our ab initio results we
      conclude that the transition is driven by molecular dissociation rather than
      disorder and that both temperature and pressure play a key role in determining
      structural changes in the fluid.

PMID- 15267447
TI  - Basis set study of classical rotor lattice dynamics.
AB  - The reorientational relaxation of molecular systems is important in many
      phenomenon and applications. In this paper, we explore the reorientational
      relaxation of a model Brownian rotor lattice system with short range interactions
      in both the high and low temperature regimes. In this study, we use a basis set
      expansion to capture collective motions of the system. The single particle basis
      set is used in the high temperature regime, while the spin wave basis is used in
      the low temperature regime. The equations of motion derived in this approach are
      analogous to the generalized Langevin equation, but the equations render
      flexibility by allowing nonequilibrium initial conditions. This calculation shows
      that the choice of projection operators in the generalized Langevin equation
      (GLE) approach corresponds to defining a specific inner-product space, and this
      inner-product space should be chosen to reveal the important physics of the
      problem. The basis set approach corresponds to an inner-product and projection
      operator that maintain the orthogonality of the spherical harmonics and provide a
      convenient platform for analyzing GLE expansions. The results compare favorably
      with numerical simulations, and the formalism is easily extended to more complex
      systems.

PMID- 15267448
TI  - Turbidity determination of the critical exponent eta in the liquid-liquid mixture
      methanol and cyclohexane.
AB  - The turbidity of the liquid-liquid mixture methanol-cyclohexane has been measured
      very near its critical point and used to test competing theoretical predictions
      and to determine the critical correlation-correction exponent eta. By measuring
      the ratio of the transmitted to incident light intensities over five decades in
      reduced temperature, we are able to determine that Ferrell's theoretical
      prediction for the turbidity explains the data with the correlation length
      amplitude xi0=0.330+/-0.003 nm and critical exponents eta=0.041+/-0.005 and
      nu=0.632+/-0.002. These values are consistent with the values measured before for
      xi0 in this system and with the exponents predicted by theory. The data allow
      five different theoretical expressions to be tested and to select two as being
      equivalent when very close to the critical point.

PMID- 15267449
TI  - Isomers of HSCO: IR absorption spectra of t-HSCO in solid Ar.
AB  - Irradiation of an Ar matrix sample containing H2S and CO (or OCS) with an ArF
      excimer laser at 193 nm yields trans-HSCO (denoted t-HSCO). New lines at 1823.3,
      931.6, and 553.3 cm(-1) appear after photolysis and their intensity enhances
      after annealing; secondary photolysis at 248 nm diminishes these lines and
      produces OCS and CO. These lines are assigned to C-O stretching, HSC-bending, and
      C-S stretching modes of t-HSCO, respectively, based on results of 13C-isotopic
      experiments and theoretical calculations. Theoretical calculations using density
      functional theories (B3LYP and PW91PW91) predict four stable isomers of HSCO: t
      HSCO, c-HSCO, HC(O)S, and c-HOCS, listed in increasing order of energy. According
      to calculations with B3LYP/aug-cc-pVTZ, t-HSCO is planar, with bond lengths of
      1.34 A (H-S), 1.81 A (S-C), and 1.17 A (C-O), and angles angle HSC congruent with
      93.4 degrees and angle SCO congruent with 128.3 degrees; it is more stable than c
      HSCO and HC(O)S by approximately 9 kJ mol(-1) and more stable than c-HOCS by
      approximately 65 kJ mol(-1). Calculated vibrational wave numbers, IR intensities,
      and 13C-isotopic shifts for t-HSCO fit satisfactorily with experimental results.
      This new spectral identification of t-HSCO provides information for future
      investigations of its roles in atmospheric chemistry.

PMID- 15267450
TI  - Interactions of D2O with methane and fluoromethane surfaces.
AB  - TOF-SIMS is used to investigate the interactions between D2O and hydrophobic
      molecules, such as CH4, CH3F, CH2F2, CHF3, and CF4, at cryogenic temperatures (15
      K). By irradiation with a 1.5-keV He+ beam, the D(+)(D2O)n ions are ejected
      efficiently from the D2O nanoclusters physisorbed on the CF4 layer due to Coulomb
      explosion: the ion yields are by about two orders of magnitude higher than those
      from a thick D2O layer via the kinetic sputtering. The D(+)(D2O)n yields decrease
      on the CHnF(4-n) layer with increasing the number of the C-H group. This is
      because the Coulombic fission is quenched due to the delocalization of valence
      holes through the C-H...H-C and C-H...D2O contacts. A pure D2O film is hardly
      grown on the CH4 layer as a consequence of intermixing whereas the D2O molecules
      basically adsorb on the surfaces of fluoromethanes, suggesting the attractive
      (water-repellent) interactions in the C-H...D2O (C-F...D2O) contacts. The C-H...O
      bond behaves like a conventional O-H...O hydrogen bond as far as the collision
      induced proton transfer reaction is concerned.

PMID- 15267451
TI  - Adsorption and reaction of methanol on clean and oxygen modified rhodium/vanadium
      surface alloys.
AB  - The dehydrogenation of methanol on Rh(111), on a Rh(111)/V subsurface alloy and
      on Rh(111) with V islands has been studied with and without preadsorbed oxygen
      using a supersonic molecular beam and temperature programmed desorption. The
      reactivity is highest for the V islands surface without oxygen. But this surface
      is deactivated due to CO dissociation. The subsurface alloy is less reactive than
      the islands, but still more active than the Rh(111) surface. The reaction
      products are carbon monoxide and hydrogen only. With preadsorbed oxygen Rh(111)
      is the most active surface, but a strong dependence of the activity on the amount
      of preadsorbed oxygen is found for all three surfaces. The reaction products with
      preadsorbed oxygen are water, hydrogen, carbon dioxide and carbon monoxide. The
      reactions follow the same mechanism on all surfaces, but the activation energy of
      the individual reaction steps is different leading to significant changes in the
      thermal desorption spectra and in King and Wells-type experiments.

PMID- 15267452
TI  - Relaxation dynamics of a polymer in a 2D confinement.
AB  - The molecular dynamics of oligomeric poly(propylene glycol) (PPG) liquids
      (MW=1000, 2000, and 4000 g/mol) confined in a two-dimensional layer-structured Na
      vermiculite clay has been studied by broadband dielectric spectroscopy. The alpha
      relaxation and the normal mode relaxation processes were studied for all samples
      in bulk and confinement. The most prominent experimental observation was that for
      the normal mode process: the relaxation rate in the clay is drastically shifted
      to lower frequencies compared to that of the bulk material. This slowing down is
      probably caused by the strongly reduced number of accessible chain conformations
      in two dimensions. Also the temperature dependence of the relaxation time for the
      normal mode process is strongly affected by the confinement. In contrast, for the
      alpha-relaxation of the confined polymers we observed only a slight increase of
      the relaxation rate at high temperatures compared to the corresponding bulk
      samples, and a decrease of its relaxation strength relative to the beta
      relaxation. Thus, the glass transition is unaffected by the 2D confinement,
      suggesting that the underlying phenomena responsible for the glass transition is
      the same as in bulk. Moreover, in the clay the intensity of the normal mode is
      stronger than that of the alpha-process, in contrast to the bulk samples where
      the opposite behavior is observed.

PMID- 15267453
TI  - The influence of bond flexibility and molecular size on the chemically selective
      bonding of In2O and Ga2O on GaAs(001)-c(2 x 8)/(2 x 4).
AB  - The surface structures formed upon deposition of In2O and Ga2O by molecular beam
      epitaxy onto the arsenic-rich GaAs(001)-c(2 x 8)/(2 x 4) surface have been
      studied using scanning tunneling microscopy and density functional theory. In2O
      initially bonds, with indium atoms bonding to second layer gallium atoms within
      the trough, and proceeds to insert into or between first layer arsenic dimer
      pairs. In contrast, Ga2O only inserts into or between arsenic dimer pairs due to
      chemical site constraints. The calculated energy needed to bend a Ga2O molecule
      approximately 70 degrees, so that it can fit into an arsenic dimer pair, is 0.6
      eV less than that required for In2O. The greater flexibility of the Ga2O molecule
      causes its insertion site to be 0.77 eV more exothermic than the In2O insertion
      site. This result shows that although trends in the periodic table can be used to
      predict some surface reactions, small changes in atomic size can play a
      significant role in the chemistry of gas/surface reactions through the indirect
      effects of bond angle flexibility and bond length stiffness.

PMID- 15267454
TI  - Dynamic contact angles under evaporation.
AB  - Wetting kinetics in the presence of heat transfer, evaporation, and Marangoni
      effect has been explored using a method used by Joanny and de Gennes [C. R. Acad.
      Sci. Ser. II 299, 279 (1984)]. The method solves for the dynamic contact angle
      alpha by equating the rate of surface work to the rate of dissipation. The result
      in the form of dynamic contact angle alpha as a function of capillary number Ca
      agrees well with existing experimental data. Qualitative comparisons have been
      made in cases where quantitative data do not exist. Finally, a form of contact
      line instability is predicted, for which some experimental justifications are
      seen.

PMID- 15267455
TI  - Molecular binding at gold transport interfaces. III. Field dependence of
      electronic properties.
AB  - The behavior of the electronic structure in a metal/molecular/metal junction as a
      function of the applied electric field is studied using density functional
      methods. Although the calculations reported here do not include the electrode
      bulk, or intermolecular interactions, and do not permit actual transport to
      occur, nevertheless they illuminate the charging, energy shift, polarization and
      orbital occupation changes in the molecular junction upon the application of a
      static electric field. Specifically, external electric fields generally induce
      polarization localization on the two cluster ends. The HOMO/LUMO gap usually
      decreases and, for large enough fields, energy levels can cross, which presages a
      change of electronic state and, if found in molecular electronic circuits, a
      change in transmission. The calculations also show changes in the geometry both
      of the molecule and the molecule/cluster interface upon application of the
      electric field. These effects should be anticipated in whole circuit studies.

PMID- 15267456
TI  - Molecular binding at gold transport interfaces. IV. Thiol chemisorption.
AB  - Alkene thiol/coinage metal molecular interfaces are relatively easy to make, and
      can result in well-ordered self-assembled monolayer films. The energetics of such
      formation is complex-differing experimental and theoretical accounts have focused
      on the nature of the binding, the energetics via different pathways (thiol
      radical, thiol or thiolate) and the geometry of binding. We report density
      functional theory calculations on a four atom gold cluster interacting with
      different (alkane, alkene, alkyne) thiolates. We find thiolate addition to be
      strongly exoergic, thiol radical to be roughly half as favorable, and thiol to be
      slightly favorable. We also find that the S-H bond can remain when the thiol
      attaches to the gold cluster, formally resulting in increased coordination on the
      sulfur atom.

PMID- 15267457
TI  - Molecular simulation of the reversible mechanical unfolding of proteins.
AB  - In this work we have combined a Wang-Landau sampling scheme [F. Wang and D.
      Landau, Phys. Rev. Lett. 86, 2050 (2001)] with an expanded ensemble formalism to
      yield a simple and powerful method for computing potentials of mean force. The
      new method is implemented to investigate the mechanical deformation of proteins.
      Comparisons are made with analytical results for simple model systems such as
      harmonic springs and Rouse chains. The method is then illustrated on a model 15
      residue alanine molecule in an implicit solvent. Results for mechanical unfolding
      of this oligopeptide are compared to those of steered molecular dynamics
      calculations.

PMID- 15267458
TI  - Stress relaxation of deformed gel in a good solvent.
AB  - A method for obtaining elastic moduli and frictional properties of gel chains,
      diagonal and off-diagonal elements of a friction tensor, from a tensile force
      relaxation of cylindrical gel that is stretched in a good solvent is presented.
      The theory to describe the relaxation is developed on the assumption that an off
      diagonal element of the friction tensor is nonzero and compared with experimental
      results obtained for the poly(acrylamide) gel in water. The experiments revealed
      that the tensile force relaxation, F(t) at a long t, was described by a function:
      F(t)=A(Fi-FS) x exp(-t/tau)+FS, where Fi, FS, and A, respectively, were tensile
      forces at the initiation and the steady state, and a constant. The tau was found
      to be proportional to a square of radius of the gel. The experiments also
      revealed that the elastic force relaxation was synchronized with a change of the
      gel diameter. The theory well elucidates the experimental results to reveal the
      bulk and shear moduli, and the diagonal and off-diagonal elements of friction
      tensor.

PMID- 15267459
TI  - Thermodynamic perturbation theory for fused sphere hard chain fluids using
      nonadditive interactions.
AB  - A model is developed for the equation of state of fused chains based on Wertheim
      thermodynamic perturbation theory and nonadditive size interactions. The model
      also assumes that the structure (represented by the radial distribution function)
      of the fused chain fluid is the same as that of the touching hard sphere chain
      fluid. The model is completely based on spherical additive and nonadditive size
      interactions. The model has the advantage of offering good agreement with
      simulation data while at the same time being independent of fitted parameters.
      The model is most accurate for short chains, small values of Delta (slightly
      fused spheres) and at intermediate (liquidlike) densities.

PMID- 15267460
TI  - The unphysical pinning of the domain growth during the separation of homopolymer
      blends near the spinodal.
AB  - We simulate model B of mesoscopic dynamic with the Flory-Huggins free energy for
      the homopolymer blend. We concentrate the study on the rescaling of the spatial
      coordinates in the model. We show that the commonly used rescaling of the spatial
      coordinates, by the function vanishing at the spinodal, leads to the unphysical
      freezing of the domains. We study the evolution of the system in two different
      processes: One is the growth process induced by the temperature quench to the
      metastable or unstable region of the phase diagram and the second is the quench
      jump process in which we first allow the system to separate below the spinodal
      and next heat it up below or above the spinodal. The proper rescaling avoiding
      the unphysical pinning of the domain growth at the spinodal is proposed.

PMID- 15267462
TI  - Self-assembly of rod-coil block copolymers.
AB  - We present a self-consistent field theory model for the self-assembly behavior of
      rod-coil block copolymers. The orientational interactions between the rods were
      modeled through a Maier-Saupe interaction, while the enthalpic interactions
      between rods and coils were modeled through a standard Flory-Huggins approach. We
      outline a "real-space" numerical approach to solve the self-consistent field
      equations for such rod-coil block copolymers. A major focus of our work is upon
      the nonlamellar phases observed in the experiments on such polymers. To develop a
      physical understanding of these phases and their regimes of occurrence, we
      compute the two-dimensional phase diagram for our model. The latter shows
      significant departures from the one-dimensional phase diagram, but matches
      qualitatively with the existing experimental results. We also present scaling
      arguments that rationalize the numerical results for the self-assembly behavior.

PMID- 15267461
TI  - Self-assembly of peptides into a beta-barrel motif.
AB  - We report the results of a study of the self-assembly of four minimalist peptide
      strands with a native beta-barrel structure. Using a soft-well potential to mimic
      cellular crowding, molecular dynamics simulations were performed in confining
      spheres of varying radii. By utilizing a previously introduced scaling factor
      lambda for the non-native hydrophobic interactions (0<lambda<1), we were able to
      study models with varying degrees of frustration. Both the thermodynamics and
      kinetics of a Go-like model (lambda=0) and a highly frustrated model (lambda=0.9)
      were studied. Additionally, we used an extrapolation technique to investigate the
      thermodynamics of assembly at intermediate values of lambda. As in our earlier
      work [J. Chem. Phys. 118, 8106 (2003)] on a connected Go-like model beta-barrel
      protein, we find that the stability of the assembled protein increases with
      decreasing sphere size, and that larger confining spheres result in increased
      assembly times. Additionally, the lambda=0 model seems to undergo distinct phase
      transitions during the assembly process. In contrast, the more frustrated model
      (lambda=0.9) appears to undergo a glasslike transition at temperatures comparable
      to the assembly temperature of the Go model, and that this transition is
      relatively nonspecific. Our results suggest the assembly process is dependent on
      both sequence and environment, with implications for the formation of
      misassembled aggregates.

PMID- 15267463
TI  - Simulation study of intra- and intermicellar ordering in triblock-copolymer
      systems.
AB  - We report a numerical study of the structure and phase behavior of a model for a
      triblock-copolymer solution. The aim of this study is to investigate the nature
      of the dense micellar phase that can form in such systems. The simulations were
      performed on a lattice model for PEO (poly(ethylene-oxide))-PPO (poly(propylene
      oxide))-PEO polymers. At high volume fractions, the structure factor of the
      amphiphile-solvent system can be mapped onto that of a monodisperse hard-sphere
      fluid. Yet, a low-density hard-sphere model cannot account for the properties of
      the dilute micellar solution. Moreover, direct inspection of the snapshots of the
      suspension show that these model triblock-copolymer micelles are neither hard,
      nor spherical, nor monodisperse.

PMID- 15267464
TI  - The shape of transmission spectra of thin films deposited on a substrate.

PMID- 15267465
TI  - Vibrational energy levels of ozone up to dissociation revisited.
AB  - Two recent papers presented calculations of the highly excited vibrational states
      of ozone. The nature and energies of these states may hold the key to the
      anomalous isotopic distribution of ozone in the atmosphere. Even though the same
      potential energy surface of Babikov et al. was used in both calculations, the
      number of bound van der Waals states reported below dissociation differed
      significantly. In order to resolve the issue we present here the results of an
      independent computation of all the bound vibrational states of (16)O(16)O(16)O
      and (16)O(16)O(18)O up to dissociation. Our methods differ from both earlier
      calculations since we use hyperspherical coordinates and a direct product
      discrete variable representation of the Hamiltonian. The results of present work
      support the existence of several van der Waals states for J=0 on this potential
      energy surface.

PMID- 15267466
TI  - Rotationally selected product pair correlation in F+CD(4)-
      >DF(nu('))+CD(3)(nu=0,N).
AB  - The title reaction was studied in a crossed-beam experiment by imaging of state
      selected products. The rotational state selection of the CD(3) products was
      achieved using (2+1) resonance-enhanced multiphoton ionization. The coincident
      information on the DF coproducts was revealed in a state-resolved manner from
      time-sliced velocity map images. Significant dependences of both the correlated
      differential cross sections and the DF vibrational branching ratios on the
      "tagged" CD(3) rotation states were found. The dynamical implications of one of
      the major findings are discussed.

PMID- 15267467
TI  - Changes in the structure of water deduced from the pressure dependence of the
      Raman OH frequency.
AB  - We report on the Raman spectra of water under high temperature and pressure
      conditions and show a discontinuity in the pressure dependence of the OH
      stretching frequency. As pressure increases, the strength of hydrogen bonding
      increases rapidly in the pressure ranges up to 0.4+/-0.1 GPa at 25 degrees C,
      1.0+/-0.1 GPa at 100 degrees C, and 1.3+/-0.1 GPa at 300 degrees C and slowly
      above these pressures. This finding clearly demonstrates the existence of
      discontinuities in the pressure response of the hydrogen bonds of water, which
      suggests a possible structural change under these conditions.

PMID- 15267468
TI  - Molecular orientation via a dynamically induced pulse-train: wave packet dynamics
      of NaI in a static electric field.
AB  - We regard the rovibrational wave packet dynamics of NaI in a static electric
      field after femtosecond excitation to its first electronically excited state. The
      following quasibound nuclear wave packet motion is accompanied by a bonding
      situation changing from covalent to ionic. At times when the charge separation is
      present, i.e., when the bond-length is large, a strong dipole moment exists and
      rotational excitation takes place. Upon bond contraction, the then covalently
      bound molecule does not experience the external field. This scenario repeats
      itself periodically. Thus, the vibrational dynamics causes a situation which is
      comparable to the interaction of the molecule with a train of pulses where the
      pulse separation is determined by the vibrational period.

PMID- 15267469
TI  - Relativistic all-electron two-component self-consistent density functional
      calculations including one-electron scalar and spin-orbit effects.
AB  - We have implemented a Gaussian basis-set two-component self-consistent field
      method based on the fourth-order nuclear-only Douglas-Kroll-Hess approximation.
      Two-electron spin-orbit effects are included using Boettger's screened-nuclear
      spin-orbit approximation. In our two-component approach, the spin-orbit
      interaction is taken into account in a variational fashion employing a
      generalized Kohm-Sham scheme which allows one to work with hybrid density
      functionals. For open-shell systems we adopt the noncollinear spin-density
      approximation. Results are presented for equilibrium bond lengths, harmonic
      vibrational frequencies, and bond dissociation energies with local spin-density,
      generalized gradient approximation, and hybrid functionals in a set of benchmark
      molecules.

PMID- 15267470
TI  - Second-order Moller-Plesset perturbation theory without basis set superposition
      error. II. Open-shell systems.
AB  - The basis set superposition error-free second-order Moller-Plesset perturbation
      theory of intermolecular interactions, based on the "chemical Hamiltonian
      approach," which has been introduced in Part I, is applied here to open-shell
      systems by using a new, effective computer realization. The results of the
      numerical examples considered (CH(4) em leader HO, NO em leader HF) showed again
      the perfect performance of the method. Striking agreement has again been found
      with the results of the a posteriori counterpoise correction (CP) scheme in the
      case of large, well-balanced basis sets, which is also in agreement with a most
      recent formal theoretical analysis. The difficulties of the CP correction in open
      shell systems are also discussed.

PMID- 15267471
TI  - Performance of the general-model-space state-universal coupled-cluster method.
AB  - The capabilities of the recently developed multireference, general-model-space
      (GMS), state-universal (SU) coupled-cluster (CC) method have been extended in
      order to enable the handling of any excited state that represents a single (S) or
      a double (D) excitation relative to the ground state. A series of calculations
      concerning the ground and excited states of the CH(+), HF, F(2), H(2)O, NH(2),
      and CH(2) molecules were carried out so as to assess the performance of the GMS
      SU CCSD method. For diatomics we have computed the entire potential energy
      curves, while for triatomics we have focused on vertical excitation energies. We
      demonstrate how a systematic enlargement of the model space enables a
      consideration of a larger and larger number of excited states. A comparison of
      the CC and full configuration interaction or large-scale CI results enables an
      assessment of the accuracy and reliability of the GMS SU CCSD method within a
      given basis set. In all cases very good results have been obtained, including
      highly excited states and those having a doubly-excited character.

PMID- 15267472
TI  - First-principle molecular dynamics with ultrasoft pseudopotentials: parallel
      implementation and application to extended bioinorganic systems.
AB  - We present a plane-wave ultrasoft pseudopotential implementation of first
      principle molecular dynamics, which is well suited to model large molecular
      systems containing transition metal centers. We describe an efficient strategy
      for parallelization that includes special features to deal with the augmented
      charge in the contest of Vanderbilt's ultrasoft pseudopotentials. We also discuss
      a simple approach to model molecular systems with a net charge and/or large
      dipole/quadrupole moments. We present test applications to manganese and iron
      porphyrins representative of a large class of biologically relevant metalorganic
      systems. Our results show that accurate density-functional theory calculations on
      systems with several hundred atoms are feasible with access to moderate
      computational resources.

PMID- 15267473
TI  - Path integral Monte Carlo approach for weakly bound van der Waals complexes with
      rotations: algorithm and benchmark calculations.
AB  - A path integral Monte Carlo technique suitable for the treatment of doped helium
      clusters with inclusion of the rotational degrees of freedom of the dopant is
      introduced. The extrapolation of the results to the limit of infinite Trotter
      number is discussed in detail. Benchmark calculations for small weakly bound
      (4)He(N)--OCS clusters are presented. The Monte Carlo results are compared with
      those of basis set calculations for the He--OCS dimer. A technique to analyze the
      orientational imaginary time correlation function is suggested. It allows one to
      obtain information regarding the effective rotational constant for a doped helium
      cluster based on a model for the rotational Hamiltonian. The renormalization of
      the effective rotational constant for (4)He(N)--OCS clusters derived from the
      orientational imaginary time correlation function is in good agreement with
      experimental results.

PMID- 15267474
TI  - Double excitations within time-dependent density functional theory linear
      response.
AB  - Within the adiabatic approximation, time-dependent density functional theory
      yields only single excitations. Near states of double excitation character, the
      exact exchange-correlation kernel has a strong dependence on frequency. We derive
      the exact frequency-dependent kernel when a double excitation mixes with a single
      excitation, well separated from the other excitations, in the limit that the
      electron--electron interaction is weak. Building on this, we construct a
      nonempirical approximation for the general case, and illustrate our results on a
      simple model.

PMID- 15267475
TI  - Quality of contracted Gaussian-type function basis sets.
AB  - The valence quality of contracted (C) Gaussian-type function (GTF) basis sets in
      molecular calculations is discussed for the first- through fourth-row atoms. The
      split-valence basis sets derived from minimal-type CGTF sets are compared with
      those derived from primitive (P) GTF sets. Using F, Cl, Br, and I atoms and their
      homonuclear diatomics as test species, we find that the split-valence CGTF sets
      have almost the same quality as PGTF sets with larger s and p expansion terms:
      for example, the (53/5), (533/53), (5333/533/5), and (53 333/5333/53) CGTF sets
      correspond approximately to the [9/5], [15/9], [19/15/5], and [22/18/7] PGTF sets
      for the first- to fourth-row atoms, respectively, where the slash separates the
      s, p, and d symmetries. For the main group atoms of the four rows, we recommend
      using the above-mentioned CGTFs or larger.